PMID- 18034070
TI  - Application of arthroscopy in anterior luxation of the shoulder.
AB  - Background. Arthroscopy is undoubtly the most comprehensive procedure for
      shoulder lesions providing even better inspection of the interior of the joint
      than conventional open procedures.<br /> Material and methods. The atrthroscopic
      Bankart procedure by suture and MITEK technique was performed in 102 patients
      (1992-2003) with acute anterior shoulder dislocations. The minimum follow-up was
      1 year. Clinical examination demostrated positive labrum pathology in all cases.
      <br /> Results. Arthroscopic treatment of acute shoulder dislocations has been
      succesfull in 100%. None of 102 patients experienced intraoperative complications
      or infections. A slight loss of abduction and minimal loss of external rotation
      was found in patients but there was no recurrence of complete dislocations or
      subluxations. <br /> Conclusions. We believe that arthroscopic surgical
      intervention after the initial shoulder dislocations can dramatically lower the
      recurrence rate and should be considered as a treatment option in young patients.

PMID- 18034071
TI  - An evaluation of executive functions in sportsmen after traumatic brain injury.
AB  - Background. A particularly difficult problem in the rehabilitation of patients
      with closed-head injuries (TBI) is executive dysfunction, i.e. difficulty in the
      transition from thinking to acting. The goal of this study was to evaluate the
      impact of premorbid sports background on the outcome of rehabilitation oriented
      towards executive functions.<br /> Material and methods. This retrospective study
      included over 80 TBI patients treated at the authors' rehabilitation centers from
      2000 to 2003, using the same program. The experimental group (E) consisted of 9
      persons actively involved in sports before their accidents. The controls (group
      K) included 9 TBI patients not involved in sports prior to the accident, matched
      to the patients in group E for age, sex, and severity of coma. In addition to
      clinical interview and observation, we used the Clinical Test of Executive
      Functions and the Neurolinguistic Test of Attention as outcome measures.<br />
      Results. Our results indicated clearly that patients who had been active in
      sports before injury showed significantly better results in both outcome
      measures, though the advantage was somewhat greater on the Clinical Test of
      Executive Functions. <br /> Conclusions. All the TBI patients we studied
      presented at baseline with serious executive dysfunction. The program of
      neurorehabilitation we applied showed good effects for the patients in both
      groups. However, those who had previously been active in sports achieved
      significantly better outcomes than those who had not. In planning and improving
      rehabilitation programs for TBI patients the possibility of a sports background
      should be taken under consideration.

PMID- 18034072
TI  - The use of the intraooperative ozone - theraphy as prophylaxis of infections in
      surgery of locomotor system with special regard to total hip plasty - a
      preliminary study.
AB  - Background. Ozone therapy - i.e. the treatment of patients by a mixture of oxygen
      and ozone - has been used for many years as a method ancillary to basic
      treatment, especially in those cases in which traditional treatment methods do
      not give satisfactory results. As it is widely known, ozone has antiseptic
      properties, specially on bacteria, ozone therapy has been used as a method of
      safeguarding tissues intraoperatively against infection with pathogenic hospital
      bacteria.<br /> Material and methods. The investigation was carried out in the
      Chair and Department of Orthopedics and Traumatology of the Locomotor System at
      the Medical University in Warsaw. For investigative procedures a prototype of
      apparatus for intraoperative ozone therapy was built and own method of
      administration of ozone was devised. The Bioethics Commission of the Medical
      University in Warsaw agreed to the proposed procedures. From 3rd June to November
      2003 this technique was administered to 83 patients who underwent total hip
      plasty with and without cement. The control group contained 80 patients who
      underwent similar procedures in 2003 without ozone therapy prophylaxis.<br />
      Results. No negative influence of the technique was observed during operative
      procedure. No adverse effects were observed in patients i.e.: wound inflammation,
      increase of postoperative pain, latency to early rehabilitation and elongation of
      hospital stay. In the observed group no septic complications were noted.<br />
      The evaluated prototype received a sympathetic reaction from the surgeons and
      middle medical staff. Troubleshooting of the prototype was minor and mainly due
      to misuse of the prototype.<br /> After preliminary investigation we can state
      that the prototype is safe to the patients and user-friendly to the medical
      staff.<br /> In the control group of 80 hip plasty two early septic complications
      were observed. The observation time of both groups was 4.6 months mean.<br />
      Conclusions. The usefulness of the proposed technique of ozone therapy in
      prophylaxis of early septic complications after elective orthopedic
      reconstructive surgery in which long tissue exposition and use of implants takes
      place still needs further clinical investigation.<br /> Complex evaluation of the
      above mentioned technique and therapeutic efficacy of the proposed apparatus must
      have long term results, which is possible after minimum 12 months from the finish
      of each surgical procedure. This is especially true to the evaluation of patients
      who underwent joint realloplasty, in whom routinely taken biomaterial in the
      initiate procedure contained pathogens (without any clinical signs of infection).

PMID- 18034073
TI  - Results of conservative treatment of "pilon" fractures.
AB  - Material and methods. From 1996 to 2002 30 cases of distal tibia epiphysis
      fractures (pilon fractures), including 4 cases of open fractures, were treated by
      conservative technique. According to the Ruedi-Allgower AO classification, there
      were 13 patients with type I fractures, 9 type II and 8 type III fractures.
      Follow up examinations were performed from 4 moths to 4 years. <br /> Results.
      Long-term results (mean 3 years) have been assessed in 8 cases as good, 12 as
      fair and 10 as bad. In 23 cases osteoarthritis of talotibiae joint has been
      found. In 16 cases there were deviations of bone axis (15 degree of varus). The
      range of movement of the joint was limited in all patients. In 18 cases there was
      no dorsiflexion. In one case shortening of the treated leg 2 cm has occured.<br
      /> Conclusions. The conservative treatment is effective for pilon fractures type
      I and II. The majority of bad results was found in type III due to the severe
      destruction of the articular surfaces. In that cases we recommend treatment by
      external fixation with corrections of deformation.

PMID- 18034074
TI  - Problems in aseptic bone necroses diagnostic imaging.
AB  - Aseptic bone necroses are a diverse group of diseases, where the bone necrosis is
      caused without participation of infectious factor. We can divide osteochondroses
      and aseptic bone necroses brought about by physical factors, some drugs and
      systemic disorders. Some locations are more frequent than others, although
      necrosis can be situated in the every bone. The knowledge of typical location,
      typical age, risk factors and clinical data usually allows to evaluate changes on
      the plain film and to make a diagnosis. MRI allows detecting the disease in the
      very early stage; also it is the conclusive examination, when the pathology on
      the plain film is invisible. On the basis of the MRI some new aseptic bone
      necroses classification systems were done, which allow planning the therapy. The
      radiologist - clinicist cooperation is always necessary to make the proper
      diagnosis. <br /> The proper use of diagnostic imaging allows making quick and
      proper diagnosis.

PMID- 18034075
TI  - Evaluation of osteoporosis and fracture risk.
AB  - Current management of osteoporosis evaluation is reported. Densitometric methods
      and results interpretation is described. Problem of risk factor in osteoporosis
      is discussed.

PMID- 18034076
TI  - Functional bracing of humeral schaft fractures in osteoporotic patients.
AB  - Introduction. There are many treatment methods in use, both surgical and non
      surgical, for fractures of the shaft of the humeral bone.<br /> Material and
      methods. We did a prospective study of the effectiveness of functional bracing
      for humeral shaft fractures in 8 selected patients with osteoporosis, aged 56-78.
      Evaluation was based on radiographic signs of bone union, the quality of
      reduction, and the functioning of the ulnar and gleno-humeral joints and the
      upper extremity as a whole. <br /> Results. In all the cases studied, good and
      fast bone union was achieved with varying degrees of residual deformation,
      without detectable influence of the latter on the functional result. <br />
      Conclusions. The method in use proved to be very effective, since early, good
      function of the injured extremity was restored and patient satisfaction was very
      high.

PMID- 18034077
TI  - The management of patients over 65 years of age with proximal humerus fractures.
AB  - Background. In patients older than 65 with osteoporosis, fractures of the
      proximal end of the humeral bone pose a difficult clinical problem. There is a
      larger body of opinion, however, favoring conservative treatment, while surgical
      intervention is most often reserved for complicated fractures.<br /> Material and
      methods. We studied 186 patients treated in the Traumatology Clinic at the Center
      for Post-Graduate Medical Education over the last 5 years.<br /> Conclusions. Our
      analysis showed that in osteoporotic fractures of the proximal epiphysis of the
      humeral bone there are very limited indications. As a general rule the best
      effects are achieved by the shortest possible duration of immobilization and
      early intervention.

PMID- 18034078
TI  - Treatment of osteoporotic pertrochanteric fractures with use of elastic Ender
      nails in aged people.
AB  - INTRODUCTION: Proximal femur fractures are often the first symptom of
      osteoporosis in old people. Proximal femur fractures in the sequence of minimal
      trauma are as the rule multifragmental and covers peritrochanteric part. We
      reviewed effectiveness of Ender technique in aged people with coexisting
      ostoporosis.<br /> MATERIAL AND METHODS: In 1995-2001 114 patients with
      osteoporotic peritrochanteric fractures were treated with Ender technique. In our
      group of patients before operation coexisted in 27 diabetes mellitus, in 52
      arteriosclerosis and in 29 patient in different degree senile dementia. We
      evaluated 76 patient after 6, 12, 18 weeks and 12 months post operatively. We
      examined range of hip motion and way of walking, on x-rays we evaluated the
      healing of fracture and shaft-neck angel. <br /> RESULTS: Clinical and
      radiological evaluation of named group showed a very good result in 45 (60%), a
      good result in 20 (28%) and a poor results in 11 (12%) of operated patients. The
      fracture healing occurred in all named group in 84% of patient in 10-24 weeks
      (mean 17 weeks).<br /> CONCLUSION: Elastic Ender nailing is a technique of choice
      in the treatment of aged people with osteoporosis and passed medical history. The
      best result of operative treatment were achieved in patient operated in <br /> 1
      day after trauma, with high physical and mental dexterity before trauma.

PMID- 18034079
TI  - Methods of operative treatment of proximal femur fractures in elderly patients
      with osteoporosis.
AB  - Introduction. Progressive osteoporosis as a cause of bone fractures is a serious
      clinical and social problem.<br /> Material and methods. We studied 465 elderly
      patients treated surgically for fractures of the proximal femur. 3rd and 4th
      degree fractures of the femoral neck according to the Garden scale were operated
      by Austin-Moore hemiarthroplasty or total hip replacement. In unstable
      peritrochanteric fractures, intramedullary Gamma nail osteosynthesis was applied
      in 69 patients, which allows for early mobilization and full weight-bearing. This
      method minimizes possible complications and mortality. <br /> Results. There were
      no fatal complications during post-surgery hospitalization. Two patients over 80
      years of age suffered decubitus ulcers. Re-osteosynthesis was not required after
      intramedullary Gamma nail osteosynthesis. In long-term follow-up we observed two
      failures after union of femoral neck fracture in younger patients.

PMID- 18034080
TI  - Complex management of osteoporotic vertebral fracture.
AB  - Background. Compression fractures of the thoraco-lumbar spine are the most common
      form of damage to the skeletal system caused by osteoporosis. These fractures are
      stable and do not produce neurological deficits. The intensity of the clinical
      symptoms depends on the degree of kyphotic distortion of the spine and the number
      of fractured vertebrae. Among the most serious consequences of such injuries are
      chronic pain, habituated poor body posture (deeper thoracic kyphosis with
      compensatory hyperlordosis in the lumbar spine), motor and functional
      limitations, reduced quality of life, and heightened risk of subsequent spinal
      fractures. <br /> Material and methods. We analyzed a group of 26 patients
      treated for spinal fractures associated with osteoporosis, in order to evaluate
      the effectiveness of the treatment methods applied.<br /> Conclusions. Our
      results indicate that the best outcomes are obtained when the period of
      immobility is reduced to a minimum and rehabilitation is commenced as early as
      possible.

PMID- 18034081
TI  - Results of vertebral fractures treatment in osteoporosis in own material.
AB  - Background. Vertebral fractures in patients with osteoporosis are the most
      serious complication of this disease. It seems to be an important therapeutic
      problem, because of the intensity of the pain syndrome. Introduction presents
      classification, imaging and differential diagnostics, presentation of therapeutic
      intervention used in clinical practice.<br /> Material and methods. The work is a
      retrospective clinical analysis of vertebral fractures treatment results from the
      period 1997- 2000. Material consists of 64 (58 women and 6 men) in average age of
      69 (56-77) cases with spine fractures and osteoporosis treated with, presented in
      introduction protocol. <br /> Results. 41% of this group declared the pain
      occurring rare, and 59% - frequently.

PMID- 18034082
TI  - Problems in the treatment of osteoporotic fractures of the lower limbs.
AB  - Based on literature and own experience, author presents epidemiology data and
      treatment strategy; diagnostics preoperative procedures, possibilities of
      conservative and a specially operative treatment of the most common osteoporotic
      fractures of the proximal femur end and pelvis. <br /> Author presents also the
      rules of the fractures prevention and post operative treatment.

PMID- 18034083
TI  - Problems in the treatment of lower limb fractures in osteoporosis.
AB  - The fractures are the clinical manifestation of osteoporosis, the most common
      metabolic bone disease. It leads do decreased mechanical resistance of bone and
      increased ability of fractures. Identification of risk factors, bone mineral
      density and bone markers measures helps to identify and control the severity of
      the problem. However, the characteristics of the disorder obliges the specific
      conditions in treatment of the traumatic lesions to the locomotor system related
      to osteoporosis. The first rule is the need to achieve the fastest mobilization
      of the patient. The choice of the treatment method should take the age and
      general condition of the patient to consideration. The work presents the
      principles of proceedings in treatment of traumatic lesions of the lower
      extremities resulting from osteoporosis with consideration of the antithrombotic
      prophylaxis. Matching the method with relation to fracture type, general
      condition of the patient, coexisting diseases as well as the center ability and
      experience is still valid condition. <br />

PMID- 18034084
TI  - Management of osteoporosis.
AB  - The fundamental goal in the treatment of osteoporosis is to prevent fractures. In
      recent years there has been intensive research on pharmaceutical agents that can
      be used to treat osteoporosis. This article presents the general principles for
      treating osteoporosis, developed on the basis of the available literature. Those
      drugs which have been approved for prescription in Poland are discussed in
      particular detail.

PMID- 18034085
TI  - Antomy of the Proximal Femur -geometry and architecture. Morphologic
      investigation and literature review.
AB  - Material and methods. To analyze morphology and endosteal anatomy of the proximal
      ends of the femur of 40 cadaver femora were x-rayed, dissected and measured.
      Various variables including trabecular pattern, calcar size, and cortical bone
      were measured and correlated. Observations were compared to literature concerns
      the various aspects of anatomy of the proximal femur. <br /> Results. One must
      recognize that much of the information that we gather in every day practice is
      two dimensional, namely, x-rays of the hip. Morphological data with three
      dimensional perspective demonstrate internal architecture of proximal femur
      including calcar femorale. Authors pointed out lower values of neck shaft angle
      than observed in other examined populations.<br /> Conclusions. They found that
      topographic and angular position of calcar femorale depends on anteversion angle.
      Shadow of the calcar on X-ray of the femur in Lauenstein's view may become
      invisible in some cases what is correlated to its real dimension. Calcar femorale
      as a anatomical structure has no strict topographic coincidence with "calcar
      resorption" observed in some total hip replacements.

PMID- 18034086
TI  - Botulin toxin A in the treatment of dynamic equinovarus foot in cerebral palsied
      children.
AB  - Background. Contracture of the triceps in the calf occurs in most CP children
      especially those with diplegia and spastic hemiplegia. The purpose of our
      research was to evaluate the effective of TB-A in the treatment of these
      contractures and the associated disturbances of the dynamic position of the foot
      in CP children.<br /> Material and methods. Thirty five CP children (19 with
      diplegia and 16 with hemiplegia) received botulinum toxin A (TBX-A-Dysport) for
      the dynamic contracture of the triceps surae muscle and secondary equinovarus
      foot deformity. These children ranged in age from 2-11 years (mean 4.6). Previous
      conservative treatment had failed to alleviate these conditions. Goniometric
      measurements of the passive range of motion and the evaluation of dynamie
      equinovarus foot were performed prior to injection of BTX-A to 54 gastrocnemius
      muscles, and again at 2, 6, and 12 weeks post injection.<br /> Results. The
      results showed high effectiveness for TBX-A, e.g. marked reduction in
      equinovarity in 47 and 49 ankle joints (68%- 78%) at 2 and 6 weeks respectively,
      and in 19 joints (35%) at 12 weeks post-treatment, and moderate reduction in 12
      (22%), 8 (15%) and 14 (26%) joints respectively. These improvements were
      statistically significant. In some children the positive effect was present up to
      16 and 20 weeks post injection. No change was found on follow-up in 5 ankle
      joints (9%) at 2 weeks and in 7 (13%) at 6 and 12 weeks. Reversion to baseline
      scores was observed in 14 ankle joints (26%). The TB-A therapy was cllosely
      integrated with physiotherapy and the use of AFO orthosis when necessary.<br />
      Conclusions. Botulin toxin therapy is effective in the treatment contractures of
      the triceps of the calf and equinovarus foot in children with cerebral palsy.

PMID- 18034087
TI  - The impact of muscle training by Kotz phasal currents on increased strength and
      mass of the medial head of the quadriceps muscle of the thigh in patients with
      degenerative disease of the femoropatellar joint.
AB  - Background. This article presents the results of research on the impact of muscle
      training using Kotz phasal currents on rehabilitation outcome in patients with
      degenerative disease of the femoropatellar joint. <br /> Material and methods.
      Our research involved 40 patients undergoing isometric exercises of the
      quadriceps muscle of the thigh. In 20 of these patients (the experimental group)
      we also applied Kotz phasal currents. In the course of rehabilitation we measured
      any changes occurring in the circumference of the thigh 10 cm from the base of
      the patella, as well as muscle strength on the Lovett scale.<br /> Results. A
      significantly greater reduction in pain was achieved in the experimental group.
      After the first two weeks, the differences between the two groups in the
      circumference of the thigh and in muscle strength were only slight, but after the
      next two weeks visible changes emerged in both parameters. In the control group
      there was slight improvement in circumference of the thigh, but muscle strength
      remained unchanged. <br /> Conclusions. The results we obtained indicate that
      training with Kotz currents and isometric exercises are an effective means of
      treatment in rebuilding muscle mass and strength.

PMID- 18034088
TI  - The pathomechanism of degenerative changes in joints.
AB  - Osteoarthritis is a slowly progressive degeneration of articular surfaces,
      leading to the disruption of the chondral layers of the joint. Modern diagnostic
      and laboratory techniques make it possible to investigate the mechanism
      underlying the changes taking place in osteoarthritis and the role of the
      molecular substances involved in this disease, i.e. matrix metalloproteinases,
      cytokines and growth factors. The pathomechanism of changes leading to
      osteochondral disruption of the joint in osteoarthritis are discussed In the
      present study.

PMID- 18034089
TI  - Radiotherapy in the prevention of heterotopic ossification after arthroplasty.
AB  - Heterotopic ossification (HO) is defined as the formation of mature lamellar bone
      in nonosseous tissues. HO is a common problem following total hip replacement
      (THR) and surgical repair of traumatic acetabular fracture (TAF). Without
      receiving any kind of prophylaxis the incidence of HO in patients with THR is
      about 30-80%. The etiology of this disorder is not well understood. The treatment
      of symptomatic HO is excision of heterotopic bone. Radiation therapy is a safe
      and effective metod for prevention of HO. The present article extensively reviews
      the clinical studies to define the role of radiotherapy for prevention of HO.

PMID- 18034091
TI  - In honor of the 75th birthday of Prof. Heinz Mittelmeier.

PMID- 18034090
TI  - Spinal orthoses.
AB  - This article presents the medical indications and contemporary technical
      capabilities in orthotic management of spine. The typical orthoses as well as
      devices that today constitute an integral part of modern therapeutic procedures
      are presented.

PMID- 18034092
TI  - Difficulties in the interpretation of radiological images of the locomotor
      system.
AB  - Normal tissue structures of the locomotor system revealed in imaging can be
      mistaken by inexperienced radiologists for lesions resulting from trauma or
      disease. The author discusses the images that most often cause diagnostic
      difficulties.

PMID- 18034093
TI  - The value of CT scans with the 3D option in the diagnosis of spinal trauma,
      defects and deformities in children and adults.
AB  - Background. The diagnostic means of 3D CT reconstruction in various spine
      disorders was evaluated.<br /> Material and methods. The material and methods a
      group of 35 patients who had CT enhanced with 3D option.<br /> Results and
      Conclusions. It has been shown than the 3D reconstructions have broadened the
      diagnostic possibilities of axial CT, especially in the field of perspective and
      wholesome evaluation of spinal bone structures.

PMID- 18034094
TI  - Clinical anatomy in the vicinity of the hip joint in magnetic resonance imaging.
AB  - Background. MRIs were obtained from 24 patients with suspicion of small pelvis
      pathology, with no indication of hip joint pathology.<br /> Results and
      Conclusions. Based on the normal descriptive and topographical anatomy of the hip
      joint and its vicinity, the authors identified on the MRIs the main bony,
      muscular, vascular and nervous structures comprising and surrounding the hip
      joint. A clinical division of the muscles surrounding the hip joints is proposed.

PMID- 18034095
TI  - The radiological image of Paget's didease.
AB  - Background. Paget's disease is a metabolic bone disease characterized by
      excessive bone resorption and activated osteoclasts. The aim of the present study
      was to examine the localization and extent of lesions, radiological traits, and
      complications.<br /> Material and methods. During the period 1981-2001. 24
      patients (14 women, 10 men) with Paget's disease were examined, using x-rays of
      the skull, spine, pelvis, and the long bones of the limbs, and computer
      tomography (1 patient) of the skull and pelvis.<br /> Results. In 15 patients
      (62,5%), the disease was monoostotic, while in 9 cases (37,5%) it was polyostic.
      The most common places for changes were in the vault of the skull (9 cases), the
      tibia (7 cases), the pelvis (5 cases), the femur (3 cases), and the lumbar spine
      (3 cases). Osteosclerotic changes dominates in the radiological picture. Three of
      the patients were in the osteolitic phase of Paget's disease.<br /> Conclusions.
      The radiological picture of fully developed Paget's disease is very
      characteristic. It is possible to make a diagnosis on the basis of conventional
      radiography.

PMID- 18034096
TI  - Radiological diagnosis of Brodie's abscess.
AB  - Background. Brodie's abscess is a kind of rare subacute or chronic osteitis. It
      is probably caused by mistreated or non-treated osteitis, or by bacteria of low
      virulence.<br /> Material and methods. In the Orthopedic and Traumatology Clinic
      of our medical school 5 patients were diagnosed with Brodie's obsecess between
      1999 and 2002. all the patients had conventional x-rays, while one also had CT
      and MRI.<br /> Results and conclusions. The typical x-ray image shows an
      osteolytic lesion with sclerotic margin in the diametophysis. Each of the 5
      patients had surgery. In 4 cases the histopatological results confirmed the
      radiological diagnosis. In one case fibrous dysplasia was found.

PMID- 18034097
TI  - Radiological picture of "unaffected" proximal femoral growth plate in children
      with unilateral Perthes disease.
AB  - Background. A changed radiological picture has Bern observed in the initial x
      rays of the unaffected proximal femoral growth plate in children with unilateral
      Perthes disease. The present study seeks to determine whether a thicker,
      horizontal growth plate in an etiological factor in Perthes disease.<br />
      Material and methods. The research involved 173 children diagnosed with
      unilateral Perthes diseas, and a control group of 174 children aged 3-10.
      Alsberg's angle was measured to detect horizontal growth plate, while x-ray
      images were examined if the growth plate was thickened.<br /> Results. In 15 of
      the children with unilateral Perthes disease, the unaffected growth plate was
      horizontal (Alsberg's anle 840-900); in 8 children, the growth plate was thicker
      and radiolucent, mostly on its lateral side. No clinical symptoms accompanied
      these changes in the unaffected hip joint in the children we studied. In the
      control group, horizontal growth plate was noticed in the case of child
      (Alsberg's angle 840).<br /> Conclusions. Transient radiographic abnormalities of
      proximal femoral growth plate are risk factors for increased incidence of Perthes
      disease in children above 3 years of age. The reason for these transient
      abnormalities of femoral growth plates is probably temporary disturbance of the
      blood supply and mechanical strain before manifestation of the symptoms of
      Perthes disease.

PMID- 18034098
TI  - Differences in lower limb bone mineral density in children with anisomelia.
AB  - Background. Lower limb discrepancy (anisomelia) can be caused by many different
      factors leading to shortening (90% of cases) or lengthening of a limb (10%
      cases). This article present the results of densitometric tests performed on
      patients treated for lower limb discrepancy in the Department of Orthopedic of
      the Silesian Academy of Medicine in the years 1997-1998.<br /> Material and
      methods. Our research involved 57 patients, 31 girls and 26 boys. The Ilizarov
      technique was used to lengthen 33 femurs and 24 tibias. The average discrepancy
      was 45 mm (48 mm in the femurs and 42 mm in the tibias), and the patients average
      age was 13,8 years (range 7-26). The test were performed with a DPX apparatus by
      the Lumar Corporation. The bone mineral density (BMD) was measured in the area of
      the shortened limb segment and compared to the results of the analogous
      measurement of the opposite limb. The height of the measurement frame was 50 mm,
      and the width was equal to the width of the bone. The measurement field was
      located in each case at a distance of 3-4 cm (on the respective bone) from the
      line of the knee joint, in order to eliminate additional density caused by growth
      cartilage and the imposition of the patella. The repeatability of the tests was
      assured by a support maintaining constant internal limb rotation of 400.<br />
      Results. A difference in BMD between the shorter limb and the opposite limb was
      found in 47 children (82,5%). The average was 16,5%, whereas it was higher in the
      shorter femurs (19,1%, range 4,5 - 68,5%) than in the tibia (14%, 5,2 - 59,8%). A
      greater degree of demineralization was found in the girls (23,5%) than in the
      boys (20%). No correlation was found between the etiology of the shortening and
      the degree of calcification.<br /> Conclusions. The results of these tests may
      have great significance in the case of densitometric monitoring of regenerated
      bone being formed in the course of lower limb by the Ilizarow method.

PMID- 18034099
TI  - A procedural model of the diagnosis and treatment of osteoid osteoma in children.
AB  - The authors propose a procedural model for diagnosing osteoid osteoma in
      children. Careful clinical examination and a thorough anamnesis can suggest the
      possibility of osteoid osteoma-like changes. The diagnosis is confirmed after
      skeleton scintigraphy and computer tomography.

PMID- 18034100
TI  - Clinical sequelae of difficulties in the interpretation of radiological images of
      the locomotor apparatus.
AB  - Working on his own obserwations, the author draws attention to numerous mistakes
      made in the evaluation of x-rays. The decision to operate is sometimes made on
      the basis of misdiagnosis resulting from erroneous descriptions. The operation is
      unsuccessful, the symptoms do not resolve, and in some cases, though fortunately
      rare, there are complications.

PMID- 18034101
TI  - Osteomyelitis: always a timely topic.
AB  - The present atudy analyzed the usefulness of particular imaging methods in the of
      non-specific inflammatory lesions in bone tissue. Examples are given
      osteomyelitic changes in unusual locations and unique courses of illness in
      patients referred to the Orthopedics Department for diagnosis or treatment.

PMID- 18034102
TI  - Digital x-ray: methodological foundations and clinical significance.
AB  - The authors discuss the principles and specifies of digital c-ray. They underline
      the clinical and economic significance, regarding the high system instalation
      costs.

PMID- 18034103
TI  - Tecnological standards of teleradiology function in orthopedics and trauma care.
AB  - Digital Image is a relatively new quality in orthopedic diagnostics, which allows
      transmitting the image instead of the patient. Digital or digitized image can be
      transmitted via Internet, e-mail or local net. Observations derived form
      literature and own experience indicate that teleradiology may effectively provide
      radiologic consultation or even improve the detailed radiologic evaluation. This
      article describes sufficiently the technologic problems of teleradiology and
      explains terminology used for this branch, what allows understanding the
      fundamentals of teleradiology even for person having little technical and
      informatics knowledge. Authors describe equipment demands and standards of
      function for teleradiologic services.

PMID- 18034104
TI  - Personality, responsibility, disability.
AB  - Introduction. Patients recovering from head trauma, whether or not they exhibit
      signs of frontal syndrome, often behave irresponsibly, and the problem of their
      moral and legal responsibility for their actions arises very often. To date,
      however, this issue has not been systematically addressed in the literature.<br
      /> Case reports. The present study is a case study of three patients, all
      physicians of different specialties who suffered head injuries resulting in coma.
      Standard neuropsychological texts administered before and after rehabilitation
      indicate improvement in all tested cognitive functions and resolution of frontal
      symptoms. However, despite their efforts none of these patients bas been able to
      return to professional work as a physician, and their personal lives are in
      disarray.<br /> Discussion and conclusions. The problem of responsibility is
      inseparable from the problem of personality and disturbances in personality
      caused by disability, especially brain damage. The irresponsible behavior
      exhibited by these patients can be traced to pre-existing character traits which
      are differently expressed after the head injury. The article suggests a new
      approach to understanding the interrelationship of such complex concept as
      personality, character morality, and responsibility in the case of a person who
      has suffered organic impairment of brain function.

PMID- 18034105
TI  - Evaluation of functionality in patients with traumatic spinal cord injury.
AB  - Background. In order to develop a better picture in the earlier stages of
      rehabilitation of the functional possibilities of patients with plegia and
      paresis resulting from spinal damage, the authors have developed a simple
      functionality scale, involving primarily motor and locomotive capacity.<br />
      Material and methods. We analyzed the progress in rehabilitation of 31 patients
      with plegia or paresis subsequent to spinal cord injury, treated in the
      Rehabilitation Clinic at the Poznan Academy of Medicine. The evaluation was
      performad 6-12 months after the injury on a 22-point scale developed for patients
      with spinal cord injury, dealing with basic motor and locomotor capacity. The
      results obtained were used to calculate the "functionality index", where full
      functionality, i.e. 44 points, is treated as 1.0.<br /> Results. The results
      indicated that the best progress in rehabilitation was achieved by young patients
      with damage on lower levels and with better initial condition.<br /> Conclusions.
      The application of this simple scale to assess functionality makes it possible to
      verify objectively the results in relation to the potential indicated by the
      level of spinal trauma. It also contributes to better patient motivation and
      active inclusion in the rehabilitation process.

PMID- 18034106
TI  - Epidemiology of Scheuermann's disease in children and adolescents.
AB  - Background. The main purpose o fan article is to draw attention to an important
      orthopedic problem - the Scheuermann's disease. The subject should be of value
      not only to the orthopedic surgeons but also to pediatricians, rehabilitation
      specialists, physiotherapists and family practitioners. The main desire of the
      authors was to remind the most important facts of this disease and pay attention
      to the epidemiology.<br /> Material and methods. Is this study, all patients
      hospitalized in Rehabilitation Center in Konstancin have been observed during the
      last 30 years, the pertentage of incidence of Scheuermann's disease has been
      counted and the distribution made according to age, sex and home environment
      (village, city).<br /> Results. The should visualise if the effectiveness of
      diagnosis and early hospitalization has been improved during last years, to show
      the ratio between both sexes in predisposition to Scheuermann's disease and to
      explain whether the place of living has any impact at more common (better)
      diagnostic system. Also to prove that Scheuermann's disease is very rare
      (controversial) before 10 years of age.<br /> Discussion and conclusions. At the
      end the short discussion has been made with respect to most interesting
      international data.

PMID- 18034107
TI  - The pathomechanism of idiopathic scoliosis: the importance of physiological
      thoracic kyphosis.
AB  - Progress in research on the parthogenesis of idiopathic scoliosis has brought
      about a better understanding of the spatial character of this deformity,
      including spinal deformation on the sagittal plane. It is now generally though
      that the reduction of physiological thoracic kyphosis, followed at a later stage
      by thoracic lordosis, is a constant component of thoracic scoliosis. The authors
      present the concept of intrathoracic scoliotic vertebral hump. Both conservative
      and surgical treatment should cosist in three-dimensional correction of
      scoliosis, with particular attention paid to the restoration of normal thoracic
      kyphosis.

PMID- 18034108
TI  - Postoperative treatment and rehabilitation after total knee arthroplasty.
AB  - Total arthroplasty is the primary surgical method used in patients with extensive
      deformations of the knee joint in the course of osteoarthritis or rheumatoid
      arthritis. Good outcome after arthroplasty depends on the proper identification
      of indications, good surgical technique, and the proper postoperative treatment
      and rehabilitation. In postoperative treatment appropriate conditions should be
      provided for healing of the damaged tissues and prevention of early and late
      complications. The aim of rehabilitation is to restore mobility in the highest
      possible range and full muscular control of the operated knee, i.e. to rebuild
      correct static and dynamic function of the joint and the entire lower limb. This
      study present a model of postoperative management and rehabilitation after total
      knee arthroplasty based on current literature and clinical experience from 597
      arthroplasties performed in 530 patients between the years 1995 and 2002.

PMID- 18034109
TI  - Posterior fixation of the cranio-cervical function.
AB  - The goal of this article is to identify the best surgical procedure in treating
      disorders of the cranio-cervical functions of varying etiology and in varying
      stages of advancement. The author discusses the methods of surgical procedure and
      evaluates the effects obtained in this own clinical material, encompassing 106
      patients treated surgically at the M. Weiss Rehabilitation Center im. Konstancin,
      Poland, between 1983 and 1999, using internal fixation with bone grafts and
      internal stabilizers. The treatment outcome was evaluated on the basis of the
      author's own three-tiered scale. An analysis of the results obtained demonstrates
      that the use of bone grafts and internal stabilizers is the best solution in the
      treatment of instability of the cranio-cervical function.

PMID- 18034110
TI  - Experiences with the internal fixation of the cervical spine.
AB  - During the period 1994-1999, 141 surgeries were performed cervical vertebra in
      the Department of Neurosurgery at the Copernicus Hospital in Lodz; 62 of these
      were posttraumatic injuries. In cases of injury to the C1-C2 complex, anterior or
      posterior fixation was applied, ora a combination of both. In injuries involving
      the segment from C3 to Th1, fixation was done with the anterior approach, using
      autogenic or allogenic implants. We present here the treatment outcome for
      posttraumatic injuries treated surgically with the use of implants.

PMID- 18034111
TI  - Early results of the surgical treatment of patients with traumatic injuries to
      the cervical spine.
AB  - In the period 1997-1999, 51 patients were surgically treated for injury to the
      cervical spine at the Rzeszow Voivodeship Hospital. There were 46 men and 5
      women, with the majority in the age group 15-20 years. The most common causes of
      injury were diving and automobile accidents. Most of these patients were referred
      to our Department for treatment 1-3 days after the injury was incurred. The
      treatment method of choice was surgery. The majority of the patients were
      referred to the Department or Rehabilitation at our hospital as soon as their
      surgical wounds had healed.

PMID- 18034112
TI  - Fixation of the cervical spine using a titanium plate.
AB  - Surgery of the cervical spine has been developing since the early twentieth
      century, but significant progress began with the appearance of the anterior
      approach, thanks to Bailley, Bedgley and Cloward, who developed a special set of
      instruments to facilitate operations using the anterior approach. In 1967 Haftek
      became the first surgeon to perform this operation in Poland; since that time the
      anterior approach has come to be in more and more general use. The first goal of
      the operation is to remove fragments of bone and intervertebral discs compressing
      the spinal cord; the second goal is to achieve good fixation of the operated
      segment of the cervical spine. In the earlier period external immobilization was
      applied, using campolite collars, Florida collars, Schanz collars, or HALO
      stabilizers. Currently immobilizing is done with titanium plates, which are well
      suited to the purpose of internal fixation of the spine.

PMID- 18034113
TI  - Spinal fixation using bone cement after cervical discoidectomy.
AB  - In 45 cases of patients in the period from 1995 to 1999 for cervical discopathy,
      polymethacrylate bone cement was used as a stabilizing material. The duration of
      hospitalization ranged from 3 to 23 days (average 7,5 days). In 38 cases (84,4%)
      one-level fixation was performed, while two-level fixation was performed in 7
      cases (15,6%). The observation period for the group in question ranged from 2 to
      48 months. No complications associated with the stabilizing material used were
      discovered. On the basis of the material here presented it would appear
      justifiable to recommend this cement as a good and safe stabilizing material in
      patients operated for cervical discopathy using the anterior approach.

PMID- 18034114
TI  - Surgical treatment of pathologiesof the craniocervical functions.
AB  - Spinal fractures at the craniocervical function require surgical treatment.
      Surgical can be preceded by direct traction of the cranium in order to set the
      fragments prior to fixation. This paper presents various methods of fixation from
      the posterior titanium loops.

PMID- 18034115
TI  - The possibilities of restoring or improving hand functions in tetraplegic
      patients.
AB  - In the immediate aftermath of severe cervical SCI, most patients present with
      complete loss of functional capacity of the hand. For some of these patients, it
      is possible during treatment to restore a certain measure of functional capacity
      in the hand for daily life activities. In the clinical material we analyzed,
      however, which included 260 patients recovering from such injuries, 45% of those
      examined presented with no functional abilities in the hand.<br /> Hand function
      in patients with tetraplegia is vitally important, since this is a decisive
      factor in determining the degree of the patient's disability and dependence on
      others. Accordingly, every effort should be made to improve or restore at least
      the simplest hand functions in tetraplegics.<br /> This report briefly discusses
      the methods used to improve functioning of the paretic hand (surgery, orthoses),
      and also the efforts made to restore some measure of function in the paralyzed
      hand by the use of an autogenic graft of musculocutaneus nerve into median nerve,
      and also by the application of functional electric stimulation (FES) using
      electrodes implanted into median and radial nerves.

PMID- 18034116
TI  - Disturbances of cognitive and emotional functions in patients with whiplash
      injuries.
AB  - The goal of this article is to present the results of research on cognitive and
      emotional disturbances in patients with the "whiplash" injuries typically
      incurred as a result of rear-end collisions. Despite considerable controversy and
      discussion surrounding the whiplash syndrome the most recent literature on the
      subject contains several reports suggesting that many of these patients complain
      of specific symptoms that are not only physical, but also cognitive, emotional,
      and even linguistic, the existence of which can be detected by standard
      neuropsychological tests. In their own research involving 58 patients with late
      "whiplash" syndrome and an equal number of normals, the authors have confirmed
      the occurrence of objective symptoms in various tests. The discussion considers
      the etiology of these symptoms in various tests. The discussion considers the
      etiology of these symptoms and the significance of the results for
      rehabilitation.

PMID- 18034117
TI  - Comparative outcome of Holmium: YAG and KTP laser disc ablation in degenerative
      cervical disc disease: results of an ongoing study.
AB  - Objective. This prospective study was designer to identify the relative efficacy
      of Holmium2100: YAG and KTP532 laser wavelengths in the treatment of broad based
      cervical disc protrusions presenting with cervical axial pain with compressive or
      non compressive radicular symptoms.<br /> Methods. Patients with chronic cervical
      pain and radicular symptoms unresponsive to conservative treatment were assessed
      with MR scans. Those with broad based disc bulges were assessed with provocative
      discography to isolate the source of pain. Percutaneous laser disc decompression
      was performad as a day case procedure on 105 patients at 108 levels under X-ray
      control via the anterior approach with side firing probes. Vernon-Mior cervical
      disability and visual analogue pain indices were used to assess the outcome of
      the procedures.<br /> Results. At a minimum follow up of 12 months 50% of
      patients demonstrated a sustained significant (excellent to good) clinical
      benefit with an index value of 50% or more while an additional 25% demonstrated
      functional improvement. No difference in outcome was identified with either
      wavelength utilized or with laser annealing or painful discal tears. At this
      juncture the cohort integrity of the study is 74%.<br /> Conclusion. The outcome
      of treatment for cervical degenerative disc disease with compressive or non
      compressive radicular symptoms with KTP or Holmium: YAG laser is identical. The
      sustained nature of the benefit after long term preoperative symptoms (mean 3,4
      years) rules out placebo effect.

PMID- 18034118
TI  - An atypical surgical solution in a hangman's fracture: case report.
AB  - Anyone who is familiar with the pathomechanism of hangman's fractures will surely
      think twice before considering this type of injury to be relatively safe, on the
      grounds that a fracture of the C2 arches creates the conditions for decompressing
      the spinal cord, while the fact that the entire posterior complex is maintaining
      the ligament connection means that the fracture is relatively stable. Doe to the
      complexity of the pathomechanism involved in fractures, it is difficult to set
      the displacement non-surgically, and it may be dangerous to do so in the event of
      uncontrolled spine distraction. This article describes the surgical solution used
      to treat patient with a hangman's fracture using the anterior and posterior
      approaches simultaneously. The surgical procedure described here made it possible
      to decompress the spinal cord, perform a solid fixation, mobilize the patient
      quickly after surgery, and initiate effective rehabilitation.

PMID- 18034119
TI  - Instrumental fixation of the cervical spine with Ti-mesh prosthesis: a
      preliminary report.
AB  - This article describes the surgical treatment of the fractured body of a cervical
      vertebra, using the Codman Ti-mesh prosthesis according to the Harms method. This
      male patient had suffered a multiple fracture of the C6 cervical body; he
      required decompression of the nerve elements of the vertebral canal by C6
      corporectomy and C5-C7 intervertebral fixation. A Ti-mesh prosthesis was filled
      with bone fragments from the fractured vertebra. A Caspar plate manufactured by
      Codman was used for C5-C7 intervertebral fixation. The chief advantages of the
      method applied here include shortening the duration of surgery and providing
      good, quick fixation.

PMID- 18034120
TI  - Fixation of high thoracic spine fractures. A case report.
AB  - Fractures of the thoracic spine are very frequently accompanied by spinal cord
      compression syndromes, including symptoms that would indicate complete severance
      of the spinal cord. The indicates a very small reverse of space, especially in
      the upper and middle segments of the thoracic spine. Even a few millimeters of
      dislocation among the fragments of broken vertebrae can disrupt the proper
      anatomical relations and produce neurological deficits. Early intervention - in
      the form of complete immobilization of the damaged spinal segment, the
      administration of Solu-Medrol in a dosage consistent with the NASCIS II
      recommendations, and early surgical treatment with full decompression of the
      nerve elements - can lead to improvement. Despite the natural splinting provided
      by the ribs and the sternum, the thoracic spine requires good fixation after the
      decompression operation, followed in short order by intensive rehabilitation.

PMID- 18034121
TI  - Austenitic steel: a basic implant material in traumatic and orthopedic surgery.
AB  - In this article the author analyzed the quality of implants made of chromium
      nickel-molybdenum austenitic steels used in traumatic and orthopedic surgery. The
      steel quality is discussed in reference to the recommendations in current
      standards. The problem of chemical composition and phase structure of the steel
      has been taken into consideration, along with its physical and chemical
      properties, with particular attention to the problem of implant corrosion. The
      complications observed in clinical practice are largely dependent on material
      factors and should be taken into account when reporting clinical outcomes.

PMID- 18034122
TI  - Surgical treatment of spinal instability: a clinical analysis of 196 cases.
AB  - Fixation of the spine, consisting in surgical stiffening of vertebrae at various
      levels, was performed in 196 cases during the period 1995-1999 in the Department
      and Clinic of Neurosurgery at the Karol Marcinkowski University of Medical
      Sciences in Poznan. In all these cases there was damage to nerve structures,
      spinal cord and/or nerve roots, accompanied by spinal instability, resulting
      mainly from injuries (144 cases), less frequently from neoplastic diseases (24
      cases), degenerative diseases (21 cases), or other causes (7 cases). There were
      154 males and 42 females ranging in age from to 69 years (mean age 37,82 +/-
      15,10). The Frankel scale was applied to assess the severity of spinal coed
      disorder: we rated 109 cases to levels A, B and C, while 87 cases were rated at
      levels D and E. The anterior approach to the spine was used in 110 cases, the
      posterolateral approach in 51 cases, and the posterior approach in 35 cases.<br
      /> Internal fixation of the cervical spine was performed in 110 cases using
      cervical plates, body cages, and clamps. In 86 cases of spinal instability in the
      thoracic and lumboscaral region fixation was performed with intrapedicular
      screws, intralaminar hooks, and "Z" plates. In addition, autogenic bone grafts
      (141 cases) and acrylic bone cement (27 cases) were used to achieve spinal
      stability.<br /> Excellent and good outcomes were achieved in 180 cases. Signs of
      neurological deficiency were intensified in 13 patients and appeared temporarily
      in 10 cases. Spinal surgery was repeated in 5 cases because of implant failure.
      Mortality amounted to 3% (6 cases).

PMID- 18034123
TI  - Internal fixation systems in the surgical treatment of spondylolisthesis.
AB  - The authors of this article describe the surgical procedure for fixation of
      spondylolisthesis using transpedicular fixation, and offer a comparative
      evaluation of the DERO, CD, C-CD, SOCON, and STRYKER systems.<br /> The
      evaluation involved 36 patients operated in the Rehabilitation Clinic at the
      Lublin Academy of Medicine during the period 1994-2000. In 11 cases the DERO
      fixation system was used; in 5 cases, fixation with CD or C-CD instrumentation;
      in 15 cases, using the SOCON system; and in 5 cases with the STRYKER
      instrumentation.<br /> Indications for surgery included pain and symptoms of
      nerve root irritation with sciatic neuralgia. The concomitant neurological
      symptoms resulted from the displacement into the vertebral canal of fragments of
      the nucleus pulposus, or from bone-related stenosis of the vertebral canal and
      intervertebral foramina.<br /> Surgical treatment involved decompression of the
      nerve elements and internal fixation. In all the cases reported here posterior
      and postero-lateral spondylodesis was performed, while in 20 cases interbody
      spondylodesis was additionally performed, in 14 cases using interbody plugs.<br
      /> The authors analyze the reasons for complications, such implants working loose
      and fatigue fractures.

PMID- 18034124
TI  - An evaluation of laser photobiostimulation as a factor supporting rehabilitation
      in spinal pain syndromes.
AB  - Spinal pain can afflict both the sick and the healthy, even those with an
      anatomically correct spine. Such complaints force many people to change
      profession or even go on disability pension. Both the social and professional
      aspects are very important, then, in the rehabilitation of these people, since
      spinal pain syndromes impair the patient's locomotor capacity and his/her ability
      to work for a living. In view of this, medical rehabilitation takes on particular
      important, and especially the laser photobiostimulation technique in use for
      several years now.<br /> Biostimulating lasers have analgesis, anti-inflammatory,
      and antiallergenic effects, and relieve muscle cramps; they also improve
      metabolism and regenerate cells and tissue. Laser photobiostimulation is an
      effective, quick, aseptic therapy, with no age limitations or side effects.

PMID- 18034125
TI  - Medical rehabilitation for patients recovering from traumatic injuries to the
      cervical spine with spinal cord damage.
AB  - This article discusses the operating premises of the rehabilitation process for
      persons with traumatic injuries to the cervical spine. The various stages in the
      rehabilitation process are described, along with the difficulties encountered by
      the rehabilitation team in the course of treatment. The problems associated with
      the future development of medical rehabilitation for SCI patients are also
      discussed.

PMID- 18034126
TI  - The occipital anchor, a nwe implant in cranio-cervical fixation: biomechanical
      and clinical aspects.
AB  - This article presents a new technical solution for cranio-cervical fixation by
      means of anchors and compares this technique with the solutions previously in
      use. The evaluation was done on the basis of biomechanical and clinical tests
      performed with particular attention to the manner of implant insertion, the
      stability of mounting in the bone, endurance for a period of time sufficient to
      guarantee spondylodesis, and spatial volume (outer dimensions) of the proposed
      solution. Clinical applications are indicated.

PMID- 18034127
TI  - Problems in treating bedsores in patients with significantly limited motor
      activity.
AB  - Bedsores are a treatment problem often encountered in patients with spinal
      injuries and other bedridden patients. It may occur in patients who do not
      receive proper nursing care. Failure to observe nursing standards may result in
      neglect, potentially leading to the death of the patient. The authors describe
      the pathomechanism of bedsores, preventive measures against bedsores in daily
      nursing practice, and methods of treatment.

PMID- 18034128
TI  - Anatomical preconditions for the postero-lateral approach to the spine.

PMID- 18034130
TI  - Introduction to cranio-cervico-thoracic orthotics.

PMID- 18034129
TI  - Ultrasonography in diagnostics of musculo-skeletal system.
AB  - This paper summarises most important indications of ultrasonography in
      diagnostics of musculo-skeletal disorders. It discusses all possible goals of US
      using high frequency, high resolution probes, different modern modalities such as
      color and power Doppler techniques.

PMID- 18034131
TI  - Antimicrobial treatment in orthopedics.
AB  - Bacterial osteomyelitis causes serious problem, despite continued progress toward
      understanding its pathophysiology and optimal management. Definitive therapy
      often requires a combined antibiotical and surgical treatment. Causative
      pathogens are most often resistant to common used antibiotics. New methods of
      local antibacterial delivery are needed.

PMID- 18034132
TI  - Basic principles for nutrition and oral supplementation in diseases of varying
      etiology, trauma, surgical operations, and reconvalescence.

PMID- 18034133
TI  - Rehabilitation on the internet.

PMID- 18034134
TI  - The bone union process: pathophysiology and clinical issues. The course of bone
      union and the physical factors contitioning its occurrence.
AB  - One of the essential elements needed to undertake the proper course of treatment
      to restore functions lost as a result of fracture is familiarity with the process
      of bone union. Despite the significant advances in treatment techniques seen in
      the last 100 years, disturbances in bone union still take place in many cases,
      rendering in impossible to restore proper limb function. The failures that occur
      in treating fractures - in the form of retarded union or pseudarthrosis, as well
      as bone inflammations - have been and remain stimuli prompting many clinicians
      and scientists to research the processes taking place in the proper physiological
      process of bone union, and to search for new methods to treat disturbances of
      these processes. The present article discusses issues involved with the
      pathophysiology of osteogenetic processes, mineralization of bone tissue and bone
      rotation, the role of angiogenesis in the process of fracture healing, and the
      pathomechanism of bone union in formation. The hormonal and physical factors
      affecting the course and stimulation are discussed, as well as methods supporting
      and stimulating the bone union processes (electrical, electromagnetic, and ultra
      sound stimulation).

PMID- 18034135
TI  - The bone union process: pathophysiology and clinical issues. Factors conditioning
      the occurrence of bone union on the molecular level.
AB  - The discovery of protein substances that fulfill transmission functions
      (cytokines) and regulatory functions (growth factors) has made it possible to
      study the processes taking place on the molecular level during bone union. The
      present article will discuss the impact of prostoglandis (pGE, pGF), growth
      factors (TGF-B, BMP, PDGF, IGF and FGF) and cytokines (IL-6, IL-11) on bone union
      processes. Contemporary views on the physiology of bone fracture healing are
      presented, and some of the factors accelerating healing are discussed.
      Familiarity with the physiology of the bone union process, and in particular the
      role played in its proper course by growth factors and tissue hormones
      (cytokines), makes it possible to exercise direct control on the molecular level
      over the various phases. The results obtained in the course of numerous clinical
      and laboratory trials give grounds for considerable hope that it will prove
      possible to exert a direct impact on bone union processes by using these agents.
      This pertains especially union processes by using these agents. This pertains
      especially to cases of disturbances in bone union (delayed union, non-union).
      Greater knowledge of the role these substances play in the various processes
      involved in proper bone union after fracture, and the development of technology
      for their manufacture on an industrial scale, will doubtless bring about
      widespread clinical application of these substances.

PMID- 18034136
TI  - The osteogenetic potential of bone-marrow mesenchymal stem cells.
AB  - Multi-potential mesenchymal marrow Wells hale the capability to differentiate
      into a wide range of connective tissue cells, including the tissues involved in
      the locomotor apparatus. Progenitor cells can be easily obtained from the bone
      marrow of adult patients, and may provide an alternative to allografts or
      autografts of bone tissue.

PMID- 18034137
TI  - A review conventional methods to evaluate bone healing and their clinical
      suitability.
AB  - The author analyses the clinical suitability of palpatory, radiological,
      ultrasound and nuclear examinations to evaluate of bone union. Attention is drawn
      to the necessity to apply these methods in parallel, in order to obtain a
      complete quantitative and qualitative picture of the process of bone tissue
      healing.

PMID- 18034138
TI  - Ultrasonographic monitoring of bone union after fractures of long bones.
AB  - Bone union after fracture was monitorem using ultrasonography to evaluate the
      progres sof 15 long bone fractures treated conservatively or surgically
      (intramedullary nail or external stabilizer). The USG images of late postfracture
      changes were assessed in 21 patients an average of 60 weeks post trauma. The
      course of changes observed in USG imaging was observed to be generally parallel
      to the indications of bone union confirmed in clinical and radiological
      examinations. The phases of echogenic changes in callus were essentially similar
      to the scheme described by other authors, but there was some delay in their
      occurrence. After an average time of 59,43 (20-486) weeks post fracture, callus
      could still be seen as a convexity or slight depression in the course of the echo
      of dense matter. The image of an echo originating from the intramedullary nail
      could still be seen for up to 15 weeks after fracture. Ultrasonography brings
      additional qualitative data on the progress of fracture healing, but one should
      keep in mind that it is subjective in nature and dependent on the operator.

PMID- 18034139
TI  - External fracture fixation in terms of the capability to monitor and simulate
      bone union processes.
AB  - This paper presents the possibilities offered by the application of Dynastab - T
      (shaft) external stabilizers in the treatment of diaphysis fractures. The measure
      system, which during fracture treatment records the changing values of stress on
      the stabilizer arm, makes it possible to use artificial intelligence techniques
      to monitor and predict the bone union process.

PMID- 18034140
TI  - The treatment of pseudarthrosis using the Ilizarov method.
AB  - This paper presents a method for treating pseudarthrosis in the lower limbs using
      the Illizarov method. 20 patients were treated, including 3 cases with infected
      false joints. Bone union was attained in cases with infected false joints. Bone
      union was attained in cases of pseudarthrosis without infection within an average
      time of 8 months. In cases of infected false joints the time required to achieve
      bone union was 12 months. On the basis of the authors' observations the method
      described here proved to be suitable for the treatment of disturbed bone union.
      The value of this method is further increased by the slow, steady correction of
      axial disorders in the limb accompanied by simultaneous equalization. Bone union
      was achieved in 94,2% of the cases studied.

PMID- 18034141
TI  - Locking intramedullary nailing in failure of bone union.
AB  - Treatment of long bone fractures carries a high risk of complications. Among them
      slow union, nonunion and implant breakage are most often. It is very important to
      choose a proper method of treatment of these patients. In 15 such cases we
      performed locked intramedullary nailing. In most cases patients with femur and
      tibia nonunion after Zespol, Polfix or plate osteosynthesis were operated on. One
      patients with open tibia fracture treated by Ilizarov method, one with plate
      breakage after humerus shaft osteosynthesis and one with nonunion which followed
      closed treatment of tibia fracture were treated. It is very important to pay
      attention to technical elements of the procedure as well as a traumatic operative
      technic.

PMID- 18034142
TI  - The application of shock waves in the treatment of delayed bone union and
      pseudoarthrosis in long bones.
AB  - Lithotripsis using shock waves generated extracorporeally was administered to 46
      patients with pseudarthrosis or delayed union of long bone fractures. From 1500
      to 3000 high energy shock waves were administered one time only on an outpatient
      basis. Anesthesia was not required. No complications were observed. Complete
      recovery was obtained in all 25 patients with delayed union, and in 12 of the 21
      patients with pseudoarthrosis (57%). The initiation of callus formation was
      observed 6-12 weeks after treatment. These results confirm that bone union can be
      stimulated by shock waves. The treatment procedure, advantages, contraindications
      and reasons for failures are discussed. This method appears to be a valuable
      supplement to the treatment of bone union disturbances.

PMID- 18034143
TI  - The influence of electrostimulation with the use of direct and alternating
      current on the corrosion of Cr-Ni-Mo steel implants.
AB  - This paper presents results of researches of influence of different methods of
      electrostimulation of a bone union on the corrosion of implants made of AISI 316
      L steel with the passive and passive-carbon layer deposited on their surface. The
      electrostimulation was carrying out for 28 days in Tyrode's physiological
      solution of temperature 36,6 +/- 10C. The pH was varying in the 7,6 - 8,6. A
      direct, pulsating and sinusoidal current was used for the electrostimulation.
      Mass decrements and corrosion damages of implants were estimated for individual
      methods of electrostimulation. Furthermore the paper presents results of
      infiltration of corrosion products. The corrosion products come into being as the
      result of stimulation of union bone with the use direct current and invasive
      methods. A ratio of the corrosion product infiltration was estimated with use of
      X-ray microanalysis.

PMID- 18034144
TI  - Pharmacological support of bone fracture healing.
AB  - Delayed bone union nor nonunion are undesirable complications of bone fractures.
      Although most fractures heal properly, there are many situations where
      acceleration of this process would be indicated. At present, there are many
      methods to support fracture healing locally. Current research is concentrated on
      substances that could accelerate this process on a systemic level. The most
      thoroughly studied agents to date are prostaglandins, calcitonin, and parathyroid
      hormone.

PMID- 18034145
TI  - Surgical treatment of advanced lumbar spondylosis.
AB  - The goal of this article is to evaluate the effectiveness of surgical treatment
      in advanced lumbar spondylosis. The research involved 100 patients, 65 men and 45
      women, treated at the Marian Weiss Rehabilitation Center in Konstancin, Poland,
      during the years 1995-1999. The patients were divided into three groups, in each
      of which a different treatment method was applied: Group A - bone spondylodesis
      without internal stabilizers; Group B - bone spondylodesis + transpedicular
      fixation; Group C - bone spondylodesis + interbody cage fusion + transpedicular
      fixation. An analysis of the result demonstrates that the best outcome for
      surgical treatment was obtained in the group using interbody cage fusion and
      transpedicular fixation, which to a large degree reduces the duration of
      immobility and allows for ealier commencement of rehabilitation.

PMID- 18034146
TI  - Internal fixation of the spine in the surgical treatment of scoliosis.
AB  - Progressive idiopathic scoliosis, despite the good effects of treatment by
      kinesitherapy and corrective corsets, continues to pose a complicated problem in
      planning surgical procedure. On the one hand, the steady growth and improvement
      of systems for three-plane correction and fixation of scoliosis improves the
      radiological and clinical outcome; on the other hand, three arises the necessity
      to choose the surgical procedure and system of implants appropriate for the given
      type, localization, and angular dimensions of the curvature. The problems faced
      by the operating surgeon include not only making the right choice of implants,
      but also arranging the transpedicular screws and hooks at the proper strategic
      points along the curvature of the spine.<br /> On the basis of clinical material
      from 200 patients surgically treated for idiopathic scoliosis, the authors
      present surgical solutions and analyze various implant systems (CD-HORIZON, DERO,
      STRYKER), made of steel or titanium, for three-plane correction and fixation of
      the spine. Attention is called to the application in the lumbar spine of
      transpedicular screws, which improve the correction and fixation of the spine and
      reduce the amount of instrumentation needed, while assuring the essential
      horizontal arrangement of the lower lumbar vertebrae.<br /> The authors' own
      experience shows that modern systems for three-plane correction and fixation of
      the spine in scoliosis exceeding 750, despite spondylodesis, do not assure the
      proper correction and biomechanical value, in comparison to the Wisconsin method,
      which combines BW distraction with Luque intersegmentary fixation.

PMID- 18034147
TI  - The rehabilitation of executive functions in patients with closed-head injuries.
AB  - One of the most difficult problems in the rehabilitation of patients with closed
      head injuries is posed by executive function disturbances, that is, difficulty in
      making the transition from thinking to acting. This article presents the working
      hypotheses and a description of a rehabilitation program developed by the
      authors, oriented directly towards training executive functions, in contract to
      the existing standard program, based on physical therapy with the addition of
      neuropsychological exercises directed towards training particular cognitive
      functions. The program consists of exercises supporting the development of not
      only cognitive and emotional-motivational elements, but also mediating
      metaprocesses and behavioral processes. In their own research involving 24
      patients the authors confirmed the existence of objective disturbances of
      executive functioning in all subjects. The patients were divided into two groups:
      a control group of 12 patients treated with the standard program, and an
      experimental group of 12 patients who received the new rehabilitation program.
      The results obtained clearly indicate the superior effectiveness of the new
      program, not only in terms of executive functions per se, but also in transfer to
      other neurosychological parameters not treated separately. The authors discuss
      the etiology of executive function disturbances and the significance of the
      results obtained for rehabilitation. The authors' Clinical Test of Executive
      Functions is also presented.

PMID- 18034148
TI  - Post-traumatic rehabilitation of the knee joint.
AB  - Early rehabilitation was administered to 44 patients (ranging in age from 5 to
      19) with post-traumatic and post-operational damage to the knee joint. A positive
      outcome for the treatment of injuries in the vicinity of the knee joint proved to
      be dependent on rehabilitation treatment, among other factors. Early commencement
      of movement and joint mobilization after injury and surgical treatment produces a
      number of positive physiological changes. The overall plan for rehabilitation is
      conditioned by the patient's psychological condition, and by the anatomical and
      functional condition of the joint. A methodology based on muscle strength
      training using isotonic or isometric work causes specific and non-specific
      changes in the muscular system. On the basis of the isometric and isotonic
      training used here in the rehabilitation process after trauma and surgery to the
      knee joint, it was determined that training based on isometric work is more
      effective in assisting the convalescence of these patients.

PMID- 18034149
TI  - The histophysiology of fracture healing.
AB  - The authors present, in somewhat simplified form, a synthetic collection of
      information pertaining to fracture healing form the histological perspective. The
      mechanisms of fracture healing are described in reference to the histological
      construction of bone, phases in the healing process, the reactions taking place
      at the fracture site, and the mechanisms for regulating these processes with
      growth and discrimination factors.

PMID- 18034150
TI  - Nutrient foramina in the diaphyses of long bones.
AB  - This paper presents the localization and number of nutrient foramina in human
      long bones. Based on the literature and their own observations, the authors
      describe the sites and courses of nutrient vessels in the humerus, radius, ulna,
      femur, tibia, fibula and other long bones.

PMID- 18034151
TI  - Influence of alternating low frequency magnetic field on formation of the osseous
      scar.

PMID- 18034152
TI  - Information on the Internet for patients with disorders of the bone and joint
      system.

PMID- 18034153
TI  - Juliusz Zaremba: In search of the roots of orthopedics, traumatology and
      rehabilitation in Cracow.

PMID- 18034154
TI  - Invalidation of TASK1 potassium channels disrupts adrenal gland zonation and
      mineralocorticoid homeostasis.
AB  - TASK1 (KCNK3) and TASK3 (KCNK9) are two-pore domain potassium channels highly
      expressed in adrenal glands. TASK1/TASK3 heterodimers are believed to contribute
      to the background conductance whose inhibition by angiotensin II stimulates
      aldosterone secretion. We used task1-/- mice to analyze the role of this channel
      in adrenal gland function. Task1-/- exhibited severe hyperaldosteronism
      independent of salt intake, hypokalemia, and arterial 'low-renin' hypertension.
      The hyperaldosteronism was fully remediable by glucocorticoids. The aldosterone
      phenotype was caused by an adrenocortical zonation defect. Aldosterone synthase
      was absent in the outer cortex normally corresponding to the zona glomerulosa,
      but abundant in the reticulo-fasciculata zone. The impaired mineralocorticoid
      homeostasis and zonation were independent of the sex in young mice, but were
      restricted to females in adults. Patch-clamp experiments on adrenal cells suggest
      that task3 and other K+ channels compensate for the task1 absence. Adrenal
      zonation appears as a dynamic process that even can take place in adulthood. The
      striking changes in the adrenocortical architecture in task1-/- mice are the
      first demonstration of the causative role of a potassium channel in
      development/differentiation.

PMID- 18034155
TI  - Pkh-kinases control eisosome assembly and organization.
AB  - Eisosomes help sequester a subgroup of plasma membrane proteins into discrete
      membrane domains that colocalize with sites of endocytosis. Here we show that the
      major eisosome component Pil1 in vivo is a target of the long-chain base (LCB,
      the biosynthetic precursors to sphingolipids)-signaling pathway mediated by the
      Pkh-kinases. Eisosomes disassemble if Pil1 is hyperphosphorylated (i) upon
      overexpression of Pkh-kinases, (ii) upon reducing LCB concentrations by
      inhibiting serine-palmitoyl transferase in lcb1-mutant cells or by poisoning the
      enzyme with myriocin, and (iii) upon mimicking hyperphosphorylation in pil1
      mutant cells. Conversely, more Pil1 assembles into eisosomes if Pil1 is
      hypophosphorylated (i) upon reducing Pkh-kinase activity in pkh1 pkh2-mutant
      cells, (ii) upon activating Pkh-kinases by addition of LCBs, and (iii) upon
      mimicking hypophosphorylation in pil1-mutant cells. The resulting enlarged
      eisosomes show altered organization. Other data suggest that Pkh signaling and
      sphingolipids are important for endocytosis. Taken together with our previous
      results that link eisosomes to endocytosis, these observations suggest that Pkh
      kinase signaling relayed to Pil1 may help regulate endocytic events to modulate
      the organization of the plasma membrane.

PMID- 18034156
TI  - Uncoupling RNA virus replication from transcription via the polymerase:
      functional and evolutionary insights.
AB  - Many eukaryotic positive-strand RNA viruses transcribe subgenomic (sg) mRNAs that
      are virus-derived messages that template the translation of a subset of viral
      proteins. Currently, the premature termination (PT) mechanism of sg mRNA
      transcription, a process thought to operate in a variety of viruses, is best
      understood in tombusviruses. The viral RNA elements involved in regulating this
      mechanism have been well characterized in several systems; however, no
      corresponding protein factors have been identified yet. Here we show that
      tombusvirus genome replication can be effectively uncoupled from sg mRNA
      transcription in vivo by C-terminal modifications in its RNA-dependent RNA
      polymerase (RdRp). Systematic analysis of the PT transcriptional pathway using
      viral genomes harboring mutant RdRps revealed that the C-terminus functions
      primarily at an early step in this mechanism by mediating both efficient and
      accurate production of minus-strand templates for sg mRNA transcription. Our
      results also suggest a simple evolutionary scheme by which the virus could gain
      or enhance its transcriptional activity, and define global folding of the viral
      RNA genome as a previously unappreciated determinant of RdRp evolution.

PMID- 18034158
TI  - Antibody evasion by the N terminus of murid herpesvirus-4 glycoprotein B.
AB  - Herpesviruses characteristically transmit infection from immune hosts. Although
      their success in escaping neutralization by pre-formed antibody is indisputable,
      the underlying molecular mechanisms remain largely unknown. Glycoprotein B (gB)
      is the most conserved component of the herpesvirus entry machinery and its N
      terminus (gB-NT) is a common neutralization target. We used murid herpesvirus-4
      to determine how gB-NT contributes to the virus-antibody interaction. Deleting gB
      NT had no obvious impact on virus replication, but paradoxically increased virion
      neutralization by immune sera. This reflected greater antibody access to
      neutralization epitopes on gH/gL, with which gB was associated. gB-NT itself was
      variably protected against antibody by O-linked glycans; on virions from
      epithelial cells it was protected almost completely. gB-NT therefore provides a
      protective and largely protected cover for a vulnerable part of gH/gL. The
      conservation of predicted glycosylation sites in other mammalian herpesvirus gB
      NTs suggests that this evasion mechanism is widespread. Interestingly, the gB-NT
      glycans that blocked antibody binding could be targeted for neutralization
      instead by a lectin, suggesting a means of therapeutic counterattack.

PMID- 18034157
TI  - Prolonged G(q) activity triggers fly rhodopsin endocytosis and degradation, and
      reduces photoreceptor sensitivity.
AB  - Rapid deactivation of the Drosophila light receptor rhodopsin, through a visual
      arrestin Arr2 and a pathway that involves a transcription factor dCAMTA, is
      required for timely termination of light responses in the photoreceptor neuron.
      Here we report that this process is also critical for maintenance of the
      photoreceptor sensitivity. In both dCAMTA- and arr2-mutant flies, the endocytosis
      of the major rhodopsin Rh1 was dramatically increased, which was mediated by a
      G(q) protein that signals downstream of rhodopsin in the visual transduction
      pathway. Consequently, the Rh1 level was downregulated and the photoreceptor
      became less sensitive to light. Remarkably, the G(q)-stimulated Rh1 endocytosis
      does not require phospholipase C, a known effector of G(q), but depends on a
      tetraspanin protein. Our work has identified an arrestin-independent endocytic
      pathway of G protein-coupled receptor in the fly. This pathway may also function
      in mammals and mediate an early feedback regulation of receptor signaling.

PMID- 18034159
TI  - An acetylation/deacetylation cycle controls the export of sterols and steroids
      from S. cerevisiae.
AB  - Sterol homeostasis in eukaryotic cells relies on the reciprocal interconversion
      of free sterols and steryl esters. Here we report the identification of a novel
      reversible sterol modification in yeast, the sterol acetylation/deacetylation
      cycle. Sterol acetylation requires the acetyltransferase ATF2, whereas
      deacetylation requires SAY1, a membrane-anchored deacetylase with a putative
      active site in the ER lumen. Lack of SAY1 results in the secretion of acetylated
      sterols into the culture medium, indicating that the substrate specificity of
      SAY1 determines whether acetylated sterols are secreted from the cells or whether
      they are deacetylated and retained. Consistent with this proposition, we find
      that acetylation and export of the steroid hormone precursor pregnenolone depends
      on its acetylation by ATF2, but is independent of SAY1-mediated deacetylation.
      Cells lacking Say1 or Atf2 are sensitive against the plant-derived allylbenzene
      eugenol and both Say1 and Atf2 affect pregnenolone toxicity, indicating that
      lipid acetylation acts as a detoxification pathway. The fact that homologues of
      SAY1 are present in the mammalian genome and functionally substitute for SAY1 in
      yeast indicates that part of this pathway has been evolutionarily conserved.

PMID- 18034160
TI  - Anti-inflammatory lipid mediator 15d-PGJ2 inhibits translation through
      inactivation of eIF4A.
AB  - The signaling lipid molecule 15-deoxy-delta 12,14-prostaglandin J2 (15d-PGJ2) has
      multiple cellular functions, including anti-inflammatory and antineoplastic
      activities. Here, we report that 15d-PGJ2 blocks translation through inactivation
      of translational initiation factor eIF4A. Binding of 15d-PGJ2 to eIF4A blocks the
      interaction between eIF4A and eIF4G that is essential for translation of many
      mRNAs. Cysteine 264 in eIF4A is the target site of 15d-PGJ2. The antineoplastic
      activity of 15d-PGJ2 is likely attributed to inhibition of translation. Moreover,
      inhibition of translation by 15d-PGJ2 results in stress granule (SG) formation,
      into which TRAF2 is sequestered. The sequestration of TRAF2 contributes to the
      anti-inflammatory activity of 15d-PGJ2. These findings reveal a novel cross-talk
      between translation and inflammatory response, and offer new approaches to
      develop anticancer and anti-inflammatory drugs that target translation factors
      including eIF4A.

PMID- 18034161
TI  - The structural basis of cyclic diguanylate signal transduction by PilZ domains.
AB  - The second messenger cyclic diguanylate (c-di-GMP) controls the transition
      between motile and sessile growth in eubacteria, but little is known about the
      proteins that sense its concentration. Bioinformatics analyses suggested that
      PilZ domains bind c-di-GMP and allosterically modulate effector pathways. We have
      determined a 1.9 A crystal structure of c-di-GMP bound to VCA0042/PlzD, a PilZ
      domain-containing protein from Vibrio cholerae. Either this protein or another
      specific PilZ domain-containing protein is required for V. cholerae to
      efficiently infect mice. VCA0042/PlzD comprises a C-terminal PilZ domain plus an
      N-terminal domain with a similar beta-barrel fold. C-di-GMP contacts seven of the
      nine strongly conserved residues in the PilZ domain, including three in a seven
      residue long N-terminal loop that undergoes a conformational switch as it wraps
      around c-di-GMP. This switch brings the PilZ domain into close apposition with
      the N-terminal domain, forming a new allosteric interaction surface that spans
      these domains and the c-di-GMP at their interface. The very small size of the N
      terminal conformational switch is likely to explain the facile evolutionary
      diversification of the PilZ domain.

PMID- 18034163
TI  - Global implications of rising rates of cesarean sections and late preterm births.

PMID- 18034162
TI  - SAGA and a novel Drosophila export complex anchor efficient transcription and
      mRNA export to NPC.
AB  - SAGA/TFTC-type multiprotein complexes play important roles in the regulation of
      transcription. We have investigated the importance of the nuclear positioning of
      a gene, its transcription and the consequent export of the nascent mRNA. We show
      that E(y)2 is a subunit of the SAGA/TFTC-type histone acetyl transferase complex
      in Drosophila and that E(y)2 concentrates at the nuclear periphery. We
      demonstrate an interaction between E(y)2 and the nuclear pore complex (NPC) and
      show that SAGA/TFTC also contacts the NPC at the nuclear periphery. E(y)2 forms
      also a complex with X-linked male sterile 2 (Xmas-2) to regulate mRNA transport
      both in normal conditions and after heat shock. Importantly, E(y)2 and Xmas-2
      knockdown decreases the contact between the heat-shock protein 70 (hsp70) gene
      loci and the nuclear envelope before and after activation and interferes with
      transcription. Thus, E(y)2 and Xmas-2 together with SAGA/TFTC function in the
      anchoring of a subset of transcription sites to the NPCs to achieve efficient
      transcription and mRNA export.

PMID- 18034164
TI  - Resuscitative procedures at birth in late preterm infants.
AB  - OBJECTIVE: Evaluate the need for resuscitative procedures at birth, in late
      prematures. STUDY DESIGN: This prospective cohort study enrolled all liveborn
      infants from 1 to 30 September 2003, with 34 to 41 weeks of gestation without
      congenital anomalies, born in 35 public hospitals of 20 Brazilian state capitals.
      Logistic regression analyzed variables associated with the need for bag and mask
      ventilation. RESULT: Of the 10 774 infants studied, 1054 were late preterms and
      485 required resuscitative measures. Of the 1054, 338 (32%) received only free
      flow oxygen, 143 (14%) were bag and mask ventilated, 27 (3%) were intubated and
      10/27 received chest compressions and/or medications. Bag and mask ventilation in
      late preterms was associated with twin gestation, maternal hypertension,
      nonvertex presentation, cesarean delivery and lower gestational age. CONCLUSION:
      Improving control of maternal hypertension, prolonging gestation for 1 to 2 weeks
      and restricting operative deliveries could decrease the need of resuscitation of
      late preterms at birth.

PMID- 18034165
TI  - Subgaleal hemorrhage with dural tear and parietal-lobe herniation in association
      with a vacuum extraction.
AB  - Use of the vacuum for operative vaginal deliveries has become more favorable with
      fewer obstetricians and family practitioners trained in the use of forceps. When
      compared with forcep-assisted deliveries, the vacuum has been associated with a
      higher incidence of subgaleal hemorrhage (SGH), cephalhematomas, skull and
      clavicular fractures, Erb's Palsy, intracranial hemorrhage and need for ICN
      admission. We report the case of an infant who developed a large SGH with midline
      dural tear and herniation of the medial aspect of the parietal lobes bilaterally
      in association with a vacuum extraction (VE) delivery. Counseling of families
      prior to instrumented delivery as to the potential complications, adherence to
      recommendations for abandoning operative vaginal delivery in favor of a cesarean
      section and close observation of those infants delivered by VE is warranted.

PMID- 18034166
TI  - False-positive results on colorimetric carbon dioxide analysis in neonatal
      resuscitation: potential for serious patient harm.
AB  - A term infant requiring resuscitation was found to have a false-positive color
      change on a colorimetric carbon dioxide device as a result of administration of
      epinephrine via an endotracheal tube. Using models of direct application and
      vapor exposure with a test lung, we discovered that epinephrine, atropine,
      infasurf and naloxone may result in false-positive color change. This false
      positive response may lead to delayed recognition of esophageal intubation.

PMID- 18034167
TI  - Congenital disorders of glycosylation type Ia as a cause of mirror syndrome.
AB  - Mirror syndrome (that is fetal hydrops with subsequent edema in the pregnant
      woman) is a rare condition. Early diagnosis is warranted, as maternal and fetal
      morbidity and mortality is increased if not diagnosed and treated properly. In
      most cases, the underlying cause remains unclear. We report a woman who has had
      two pregnancies complicated by mirror syndrome. Congenital disorder of
      glycosylation type Ia (CDG-Ia) was identified as the underlying fetal disease in
      both cases.

PMID- 18034168
TI  - Neonatal follicular ovarian hemorrhagic cyst.

PMID- 18034171
TI  - G2A plays proinflammatory roles in human keratinocytes under oxidative stress as
      a receptor for 9-hydroxyoctadecadienoic acid.
AB  - G2A is a stress-inducible G protein-coupled receptor for oxidized free fatty
      acids, such as 9-hydroxyoctadecadienoic acid (HODE). As skin is routinely and
      pathologically exposed to many oxidative stresses such as UV radiation, chemical
      agents, and inflammation that might induce both G2A expression and production of
      G2A ligands, we examined G2A function in human keratinocytes. G2A was expressed
      in human epidermis, normal human epidermal keratinocytes (NHEK), and an
      immortalized human keratinocyte cell line (HaCaT). 9(S)-HODE evoked intracellular
      calcium mobilization and secretion of cytokines, including IL-6, IL-8, and GM-CSF
      in NHEK cells. These responses became prominent in HaCaT cells by overexpression
      of G2A. 9(S)-HODE inhibited proliferation of NHEK cells by suppressing DNA
      synthesis and arresting the cell cycle in the G0/1-phase. On the other hand,
      13(S)-HODE, another major oxidative product from linoleate, showed little or no
      effect on either cytokine secretion or on proliferation in NHEK cells. A small
      interfering RNA designed to downregulate G2A caused suppression of 9(S)-HODE
      induced inhibitory effects on proliferation of NHEK cells. UVB and H(2)O(2)
      induced G2A expression and caused oxidation of linoleate to produce 9-HODE in
      HaCaT cells. These results suggest that 9-HODE-G2A signaling plays
      proinflammatory roles in skin under oxidative conditions.

PMID- 18034172
TI  - Polymorphisms in the IL-12beta and IL-23R genes are associated with psoriasis of
      early onset in a UK cohort.

PMID- 18034175
TI  - The impact of architectural design upon the environmental sound and light
      exposure of neonates who require intensive care: an evaluation of the Boekelheide
      Neonatal Intensive Care Nursery.
AB  - OBJECTIVES: To evaluate the differences in environmental sound, illumination and
      physiological parameters in the Boekelheide Neonatal Intensive Care Unit (BNICU),
      which was designed to comply with current recommendations and standards, as
      compared with a conventional neonatal intensive care unit (CNICU). STUDY DESIGN:
      Prospectively designed observational study. RESULT: Median sound levels in the
      unoccupied BNICU (37.6 dBA) were lower than the CNICU (42.1 dBA, P<0.001). Median
      levels of minimum (6.4 vs 48.4 lux, P<0.05) and maximum illumination (357 vs 402
      lux, P<0.05) were lower in the BNICU. A group of six neonates delivered at 32
      weeks gestation showed significantly less periodic breathing (14 vs 21%) and
      awake time (17.6 vs 29.3%) in the BNICU as compared to the CNICU. CONCLUSION:
      Light and sound were both significantly reduced in the BNICU. Care in the BNICU
      was associated with improved physiological parameters.

PMID- 18034176
TI  - Flooring choices for newborn ICUs.
AB  - Floors are a major element of newborn intensive care unit (NICU) construction.
      They provide visual cues, sound control, and with certain materials, some degree
      of physical comfort for workers. Flooring materials may entail a significant cost
      for installation and upkeep and can have substantial ecological impact, both in
      the choice of the flooring itself, as well as the substances used to clean it. In
      this article the important aspects to consider for each factor are explored and
      recommendations are offered for appropriate choices in various NICU areas.

PMID- 18034178
TI  - Impact of a family-centered care initiative on NICU care, staff and families.
AB  - OBJECTIVE: Family-centered care is becoming a standard of care in neonatal
      intensive care units (NICUs). The purpose of this study was to evaluate the
      impact of a national program designed to promote family-centered care in NICUs
      and to provide information and comfort to families during the NICU
      hospitalization of their newborn. STUDY DESIGN: A quasi-experimental, post-only
      design was utilized, examining eight March of Dimes NICU Family Support((R))
      (NFS) sites. Data were gathered via telephone interviews with NICU administrators
      and surveys of both NICU staff and NICU families. RESULT: NICU administrators
      interviewed identified benefits of NFS, including culture change and additional
      support to families. Surveys of NICU staff showed that NFS enhances the overall
      quality of NICU care resulting in less stressed, more informed and confident
      parents. Surveys of NICU families showed that NFS both reduced their stress and
      made them feel more confident as their baby's parent. CONCLUSION: March of Dimes
      NFS has had a positive impact on the stress level, comfort level and parenting
      confidence of NICU families. In addition, it has enhanced the receptivity of
      staff to the presence and benefits of family-centered care.

PMID- 18034179
TI  - Results of the premature birth national need-gap study.
AB  - OBJECTIVE: Family-centered care is a standard of practice in neonatal intensive
      care units (NICUs). The purpose of the study was to assess successes and
      opportunities for improvement with parents' experiences and involvement in their
      premature infants' care in NICUs. STUDY DESIGN: Researchers' surveyed 502 parents
      whose children were currently < or =30 months old, had been born at a gestational
      age < or =36 weeks and had gone through or were currently in NICUs. RESULT: Most
      parents of premature infants were reasonably satisfied with the access, attention
      and information received from physicians and nurses in the NICU. However,
      approximately one-fourth were only moderately satisfied and nearly 10% were
      dissatisfied. CONCLUSION: While progress has been made in meeting the needs of
      parents in the NICU, more work needs to be carried out to improve family-centered
      care efforts. Specific attention should be given to providing more information
      and interaction opportunities for families, which may ultimately improve NICU
      outcomes.

PMID- 18034180
TI  - Recommended standards for the newborn ICU.

PMID- 18034181
TI  - Transitional hypothermia in preterm newborns.
AB  - Hypothermia remains a significant challenge in the initial care of premature
      infants. Although a number of prevention strategies have been identified,
      hypothermia is still a common event, especially in extremely low birth weight
      infants. Using data from four centers, we documented an incidence of hypothermia
      on admission to the neonatal intensive care unit from the delivery room of 31-78%
      for infants <1500 g birth weight. Increased efforts will be necessary to prevent
      early hypothermia in very preterm infants, especially with respect to the
      environmental conditions of the delivery room itself.

PMID- 18034182
TI  - The development of potentially better practices to support the neurodevelopment
      of infants in the NICU.
AB  - OBJECTIVE: To review the existing evidence used to identify potentially better
      care practices that support newborn brain development. STUDY DESIGN: Literature
      review. RESULT: Sixteen potentially better practices are identified and grouped
      into two operational clinical bundles based upon timing for recommended
      implementation. CONCLUSION: Existing evidence supports the implementation of
      selected care practices that potentially may support newborn brain development.

PMID- 18034183
TI  - Implementing potentially better practices to support the neurodevelopment of
      infants in the NICU.
AB  - OBJECTIVE: The purpose of the Vermont Oxford Neonatal Quality Improvement
      Collaborative 2005 was to explore improvements related to the physical
      environment of the newborn intensive care unit (NICU) in order to optimize the
      neurodevelopmental outcome of newborns. STUDY DESIGN: Five centers were involved
      in a focus group examining NICU environmental design and its impact on the
      neurodevelopmental outcome of the neonate. Using an evidence-based approach, the
      group identified 16 potentially better care practices. This article describes the
      implementation approaches for some of these practices. The practice areas include
      tactile stimulation, providing early exposure to mother's scent, minimizing
      exposure to noxious odors, developing a system for noise assessment of the NICU
      acoustic environment, minimizing ambient noise in the infants environment, and
      preservation of sleep. RESULT: Approaches to implementation were center specific.
      Optimizing neurodevelopment of the newborn was the desired goal, but this outcome
      is difficult to measure with a limited number of subjects over a short study
      period. Many of the changes although intuitively beneficial are difficult to
      measure. Education of all participants was considered essential to the process of
      implementation. CONCLUSION: The process of collaborative quality improvement is
      useful in identifying ways to optimize the physical environment of the NICU to
      improve the neurodevelopmental outcome of the neonate.

PMID- 18034184
TI  - Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations.
AB  - Germline mutations in the BRCA1 or BRCA2 tumour-suppressor genes are strong
      predictors of breast and/or ovarian cancer development. The contribution of these
      mutations to breast cancer risk within any specific population is a function of
      both their prevalence and their penetrance. Mutation prevalence varies among
      ethnic groups and may be influenced by founder mutations. Penetrance can be
      influenced by mutation-specific phenotypes and the potential modifying effects of
      the patient's own genetic and environmental background. Although estimates of
      both mutation prevalence and mutation penetrance rates are inconsistent and
      occasionally controversial, understanding them is crucial for providing accurate
      risk information to each patient.

PMID- 18034185
TI  - Innovations in image-guided radiotherapy.
AB  - The limited ability to control for the location of a tumour compromises the
      accuracy with which radiation can be delivered to tumour-bearing tissue. The
      resultant requirement for larger treatment volumes to accommodate target
      uncertainty restricts the radiation dose because more surrounding normal tissue
      is exposed. With image-guided radiotherapy (IGRT) these volumes can be optimized
      and tumoricidal doses can be delivered, achieving maximal tumour control with
      minimal complications. Moreover, with the ability of high-precision dose delivery
      and real-time knowledge of the target volume location, IGRT has initiated the
      exploration of new indications for radiotherapy, some of which were previously
      considered infeasible.

PMID- 18034186
TI  - Cell-to-cell fusion as a link between viruses and cancer.
AB  - The ability to fuse cells is shared by many viruses, including common human
      pathogens and several endogenous viruses. Here we will discuss how cell fusion
      can link viruses to cancer, what types of cancers it can affect, how the
      existence of this link can be tested and how the hypotheses that we propose might
      affect the search for human oncogenic viruses. In particular, we will focus on
      the ability of cell fusion that is caused by viruses to induce chromosomal
      instability, a common affliction of cancer cells that has been thought to
      underlie the malignant properties of cancerous tumours.

PMID- 18034187
TI  - Differential in vivo requirements for oligomerization during Groucho-mediated
      repression.
AB  - The Groucho (Gro)/transducin-like enhancer of split family of transcriptional
      corepressors are implicated in many signalling pathways that are important in
      development and disease, including those mediated by Notch, Wnt and Hedgehog.
      Here, we describe a genetic screen in Drosophila that yielded 50 new gro alleles,
      including the first protein-null allele, and has two mutations in the conserved Q
      oligomerization domain that have been proposed to have an essential role in
      corepressor activity. One of these latter mutations, encoding an amino-terminal
      protein truncation that lacks part of the Q domain, abolishes oligomerization in
      vitro and renders the protein unstable in vivo. Nevertheless, the mutation is not
      a null: maternal mutant embryos have intermediate segmentation phenotypes and
      relatively normal terminal patterning suggesting that the mutant protein retains
      partial corepressor activity. Our results show that homo-oligomerization of Gro
      is not obligatory for its action in vivo, and that Gro represses transcription
      through more than one molecular mechanism.

PMID- 18034188
TI  - Reduction of endoplasmic reticulum Ca2+ levels favors plasma membrane surface
      exposure of calreticulin.
AB  - Some chemotherapeutic agents can elicit apoptotic cancer cell death, thereby
      activating an anticancer immune response that influences therapeutic outcome. We
      previously reported that anthracyclins are particularly efficient in inducing
      immunogenic cell death, correlating with the pre-apoptotic exposure of
      calreticulin (CRT) on the plasma membrane surface of anthracyclin-treated tumor
      cells. Here, we investigated the role of cellular Ca(2+) homeostasis on CRT
      exposure. A neuroblastoma cell line (SH-SY5Y) failed to expose CRT in response to
      anthracyclin treatment. This defect in CRT exposure could be overcome by the
      overexpression of Reticulon-1C, a manipulation that led to a decrease in the
      Ca(2+) concentration within the endoplasmic reticulum lumen. The combination of
      Reticulon-1C expression and anthracyclin treatment yielded more pronounced
      endoplasmic reticulum Ca(2+) depletion than either of the two manipulations
      alone. Chelation of intracellular (and endoplasmic reticulum) Ca(2+), targeted
      expression of the ligand-binding domain of the IP(3) receptor and inhibition of
      the sarco-endoplasmic reticulum Ca(2+)-ATPase pump reduced endoplasmic reticulum
      Ca(2+) load and promoted pre-apoptotic CRT exposure on the cell surface, in SH
      SY5Y and HeLa cells. These results provide evidence that endoplasmic reticulum
      Ca(2+) levels control the exposure of CRT.

PMID- 18034189
TI  - 4-hydroperoxy-cyclophosphamide mediates caspase-independent T-cell apoptosis
      involving oxidative stress-induced nuclear relocation of mitochondrial
      apoptogenic factors AIF and EndoG.
AB  - Apoptosis is a major mechanism of treatment-induced T-cell depletion in leukemia
      and autoimmune diseases. While 'classical' apoptosis is considered to depend on
      caspase activation, caspase-independent death is increasingly recognized as an
      alternative pathway. Although the DNA-damaging drug cyclophosphamide (CY) is
      widely used for therapy of hematological malignancies and autoimmune disorders,
      the molecular mechanism of apoptosis induction remains largely unknown. Here, we
      report that treatment of Jurkat, cytotoxic, and primary leukemic T cells with an
      activated analog of CY, 4-hydroperoxy-cyclophosphamide (4-OOH-CY), induces
      caspase activation and typical features of apoptosis, although cell death was not
      prevented by caspase inhibition. Also depletion of murine thymocytes and
      splenocytes after CY treatment in vivo was not inhibited by Z-Val-Ala-DL-Asp
      fluoromethylketone (Z-VAD.fmk). Caspase-8 and receptor-induced protein (RIP) were
      dispensable for 4-OOH-CY-mediated apoptosis, while overexpression of Bcl-2 was
      partially protective. 4-OOH-CY treatment induced reactive oxygen species
      production, upregulation of Bax, and nuclear relocation of the mitochondrial
      factors apoptosis-inducing factor (AIF) and endonuclease G (EndoG). The
      antioxidant N-acetyl-L-cysteine substantially inhibited conformational changes of
      Bax, loss of mitochondrial membrane potential, nuclear relocation of
      mitochondrial factors, and apoptosis induction in 4-OOH-CY-treated T cells. These
      results strongly indicate that oxidative damage-induced nuclear translocation of
      AIF and EndoG in 4-OOH-CY-treated T cells might represent an alternative death
      pathway in the absence of caspase activity.

PMID- 18034190
TI  - RelA/NF-kappaB recruitment on the bax gene promoter antagonizes p73-dependent
      apoptosis in costimulated T cells.
AB  - The balance between antiapoptotic and proapoptotic proteins of the Bcl-2 family
      is critical in determining the fate of T cells in response to death stimuli.
      Proapoptotic genes, such as bax, are generally regulated by the p53 family of
      transcription factors, whereas NF-kappaB subunits can activate the transcription
      of antiapoptotic Bcl-2 members. Here, we show that CD28 activation protects
      memory T cells from irradiation-induced apoptosis by both upregulating bcl-xL and
      inhibiting bax gene expression. We found that p73, but not p53, binds to and
      trans-activates the bax gene promoter in irradiated T cells. The activation of
      RelA/NF-kappaB subunit in CD28 costimulated T cells and its binding onto the bax
      gene promoter results in suppression of bax transcription and decrease in both
      p73 and RNA polymerase II recruitment in vivo. RelA recruitment on the bax gene
      promoter is also accompanied by the lost of p300 binding and the parallel
      appearance of histone deacetylase-1-containing complexes. These findings identify
      RelA/NF-kappaB as a critical regulator of T-cell survival by affecting the
      balance of Bcl-2 family members.

PMID- 18034191
TI  - Anaesthesia in retinopathy of prematurity treatment.

PMID- 18034192
TI  - Late ocular manifestation of a childhood venous-lymphatic malformation.

PMID- 18034193
TI  - Intravitreal triamcinolone and bevacizumab combination therapy for refractory
      choroidal neovascularization with retinal angiomatous proliferation.

PMID- 18034194
TI  - Spontaneous involution of choroidal neovascularization secondary to rubella
      retinopathy: reply to Veloso, Costa, Orefice, and Orefice.

PMID- 18034195
TI  - Pain response and follow-up of patients undergoing panretinal laser
      photocoagulation with reduced exposure times.
AB  - PURPOSE: We performed a study of laser panretinal photocoagulation in 20 patients
      with proliferative retinopathy. We compared short exposure, high-energy laser
      settings with conventional settings, using a 532 nm, frequency doubled, Neodymium
      Yag laser and assessed the patients in terms of pain experienced and
      effectiveness of treatment. METHODS: Twenty patients having panretinal
      photocoagulation for the first time underwent random allocation to treatment of
      the superior and inferior hemi-retina. Treatment A used 'conventional'
      parameters: exposure time 0.1 s, power sufficient to produce a visible grey-white
      burns, spot size 300 microm. The other hemi- retina was treated with treatment B
      using exposure 0.02 s, 300 microm and sufficient power to have similar endpoint.
      All patients were asked to evaluate severity of pain on a visual analogue scale.
      (0=no pain, 10=most severe pain). All patients were masked as to the type of
      treatment and the order of carrying out the treatment on each patient was
      randomised. Patients underwent fundus photography and were followed up for 6-45
      months. RESULTS: Seventeen patients had proliferative diabetic retinopathy, two
      had ischaemic central retinal vein occlusion and one had ocular ischaemic
      syndrome. The mean response to treatment A was 5.11, compared to 1.40 treatment
      B, on the visual analogue scale, which was statistically significant (P=0.001).
      All patients preferred treatment B. Further treatments, if required, were
      performed with treatment B parameters and long-term follow-up has shown no
      evidence of undertreatment. CONCLUSIONS: Shortening exposure time of retinal
      laser is significantly less painful but equally effective as conventional
      parameters.

PMID- 18034196
TI  - The Cataract National Dataset electronic multi-centre audit of 55,567 operations:
      updating benchmark standards of care in the United Kingdom and internationally.
AB  - AIMS: To pilot the use of the Cataract National Dataset (CND) using multi-centre
      data from Electronic Patient Record (EPR) systems and to demonstrate the ability
      of the CND to deliver certain of its intended benefits, including detailed
      preoperative profiling of cataract surgery patients and updating of benchmark
      standards of care in the NHS and beyond. METHODS: NHS departments using EPR
      systems to collect a minimum preoperative, anaesthetic, operative and
      postoperative data set, the CND, were invited to submit data, which were remotely
      extracted, anonymised, assessed for conformity and completeness, and analysed.
      RESULTS: Four-hundred and six surgeons from 12 NHS Trusts submitted data on
      55,567 cataract operations between November 2001 and July 2006 (86% from January
      2004). Mean age (SD) was 75.4 (10.4) years, 62.0% female. Surgery was for first
      eyes in 58.5%, under local anaesthesia in 95.5% and by phacoemulsification in
      99.7%. Trainees performed 33.9% of operations. Preoperative visual acuity (VA)
      was 6/12 or better in 42.9% eyes overall, in 35.3% first eyes and in 55.3% second
      eyes. Complication rates included the following: posterior capsule rupture and/or
      vitreous loss of 1.92%, simple zonule dialysis of 0.46% and retained lens
      fragments of 0.18%. Postoperative VA of 6/12 or better (and 6/6 or better) was
      achieved for 91.0% (45.9%) of all eyes, 94.7% (51.0%) of eyes with no co
      pathologies and 79.9% (30.2%) of eyes with one or more co-pathologies
      respectively. CONCLUSIONS: The CND is fit for purpose, is able to deliver useful
      benefits and can be collected as part of routine clinical care via EPR systems.
      This survey confirms shifts in practice since the 1997-1998 UK National Survey
      with full conversion to phacoemulsification, better preoperative acuity, a
      halving of the surgical 'index' benchmark complication of posterior capsule
      rupture and/or vitreous loss, and improved VA outcomes.

PMID- 18034197
TI  - E1A-expressing adenoviral E3B mutants act synergistically with chemotherapeutics
      in immunocompetent tumor models.
AB  - The majority of clinical trials evaluating replication-selective oncolytic
      adenoviruses utilized mutants with immunomodulatory E3B genes deleted, likely
      contributing to the attenuated efficacy. We investigated whether an intact immune
      response could contribute to the observed improved efficacy in response to
      combinations with chemotherapeutics. Seven carcinoma cell lines were evaluated by
      combining viral mutants; dl309 (DeltaE3B), dl704 (DeltaE3gp19K), dl312 (DeltaE1A)
      or wild-type Ad5 with the commonly used clinical drugs cisplatin and paclitaxel.
      Synergistic effects on cell death were determined by generation of combination
      indexes in cultured cells. In vivo tumor growth inhibition was achieved by
      virotherapy alone and was most efficacious with wild-type virus and least with
      the DeltaE3B mutant. Significantly higher efficacy was observed when the viruses
      were combined with drugs. The greatest enhancement of tumor inhibition was in
      combination with the DeltaE3B mutant restoring potency to that of Ad5 wild-type
      levels, observed only in animals with intact immune response. Increases in
      infectivity, viral gene expression and replication were identified as potential
      mechanisms contributing to the synergistic effects. Our results suggest that the
      attenuation of DeltaE3B mutants can be overcome by low doses of chemotherapeutics
      only in the presence of an intact immune response indicating a role for T-cell
      mediated functions.

PMID- 18034198
TI  - Variability in the preoperative management of infants with hypoplastic left heart
      syndrome.
AB  - Infants with hypoplastic left heart syndrome (HLHS) commonly undergo initial
      surgical palliation during the first week of life. Few data exist on optimal
      preoperative management strategies; therefore, the management of these infants
      prior to surgery is anecdotal and variable. To more fully define this variability
      in preoperative care of infants with HLHS, a survey was designed to describe
      current preoperative management practices in the infant with HLHS. The
      questionnaire explored management styles as well as preoperative monitoring
      techniques and characteristics of the respondent's health care institution. The
      responses were compiled and are reported. A striking lack of consistency in
      preoperative management techniques for infants with HLHS is apparent. The impact
      of these preoperative strategies is unknown. Despite challenges in anatomic and
      hemodynamic variability at presentation, a prospective randomized controlled
      trial comparing ventilatory management techniques, enteral feeding strategies,
      and the utility of various monitoring tools on short- and long-term outcome is
      needed.

PMID- 18034199
TI  - The effect of different reduction mandibuloplasty types on lower face width and
      morphology.
AB  - Mandibular angle ostectomy (MAO) and mandibular angle-splitting ostectomy (MASO)
      are the main surgical approaches for the aesthetic correction of a square and
      broad lower face. However, few data exist on the changes in lower face width and
      morphology after two different forms of reduction mandibuloplasty. The sample in
      the current study consisted of 42 Chinese patients: 22 who underwent MAO and 20
      who received MASO. The standard frontal and lateral cephalometric radiographs
      were taken preoperatively and 1 year postoperatively. Some landmarks and
      reference lines from these radiographs were selected for measurement and
      evaluation of the changes in lower face width and lateral morphology of the
      mandible. The results demonstrated that both MAO and MASO can reduce the bigonial
      distance (MAO group mean, 10.4 mm; MASO group mean, 6.2 mm) and the frontal width
      of the lower face (MAO group mean, 15.4 mm; MASO group mean, 7.6 mm). However,
      further comparison showed that lower face width apparently is decreased more by
      MAO (10.4 mm) than by MASO (6.2 mm). In the lateral radiographs, gonial and
      mandibular plane angles were found to be significantly increased in MAO patients
      postoperatively (MAO group mean, 13.3 and 10.0 degrees, respectively), but only
      slight changes in these two angles were seen after MASO (MASO group mean, 1.6 and
      1.5 degrees, respectively). This study suggests that MAO and MSAO can effectively
      reduce lower face width, but brings about some different aesthetic results.

PMID- 18034200
TI  - Mastopexy after massive weight loss: extended chest wall-based flap associated
      with a loop of pectoralis muscle.
AB  - Mammaplasty for patients who have experienced massive weight loss involves some
      concepts that differ from those that apply to mammaplasty for normal patients.
      Breast anatomic characteristics make this procedure a very challenging situation.
      The authors present their experience with a new mammaplasty technique using an
      extended thoracic wall flap associated with a loop of pectoralis. This procedure
      is a simple and reproducible method for patients with massive weight loss that
      results in a pleasing breast shape and long-lasting results.

PMID- 18034201
TI  - Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese:
      identification of 17 novel mutations and its genetic heterogeneity.
AB  - Wilson disease (WD), an autosomal recessive disorder of copper transport, is the
      most common inherited liver disorder in Hong Kong Chinese. This was the first
      local study to elucidate the molecular basis and establish an effective DNA-based
      diagnostic protocol. The ATP7B genes of 65 patients were amplified by polymerase
      chain reaction (PCR) and sequenced. Haplotype analysis was performed using
      D13S301, D13S314, and D13S316. The p.L770L/p.R778L status in 660 subjects was
      determined to estimate WD prevalence. Allele age of p.R778L was determined by the
      smallest homozygosity region between D13S301 and D13S270. We identified 42
      different mutations with 17 being novel. p.R778L (17.3%) was the most prevalent.
      Exons 2, 8, 12, 13, and 16 harbored 70% mutations. Thirty-two haplotypes were
      associated with WD chromosomes. The estimated prevalence rate was 1 in 5,400.
      Three out of 660 normal subjects had p.L770L/p.R778L. In the remaining 657
      individuals, neither p.L770L nor p.R778L was found. We characterized a Hong Kong
      Chinese-specific ATP7B mutation spectrum with great genetic diversity. Exons 2,
      8, 12, 13, and 16 should be screened first. The perfect linkage disequilibrium
      suggested that p.R778L and its private polymorphism p.L770L originated from a
      single ancestor. This East-Asian-specific mutation p.R778L/p.L770L is aged at
      least 5,500 years.

PMID- 18034202
TI  - Infection of total hip prosthesis by Mycobacterium tuberculosis and Mycobacterium
      chelonae in a patient with rheumatoid arthritis.
AB  - Atypical mycobacterial infections of the musculoskeletal system are very rare and
      are generally associated with predisposing factors, such as trauma, use of
      corticosteroids, or an immunocompromised state. There have only been three
      reports of Mycobacterium chelonae prosthetic infection of which two cases were
      associated with total hip arthroplasty and one with total knee arthroplasty and
      no reports of both Mycobacterium tuberculosis and M. chelonae occurring in the
      same joint. We report a case of a patient with rheumatoid arthritis treated with
      low-dose methotrexate (15 mg/week) who developed infection with both M.
      tuberculosis and M. chelonae after the revision of a prosthetic hip. Joint
      infections by mycobacteria are clinically indistinguishable from those caused by
      more common bacterial pathogens and, therefore, diagnosis is often delayed.
      Recurrent prosthetic hip infections, particularly in immunosuppressive patients,
      should alert the physician to consider the possibility of both tuberculous and
      atypical mycobacterial infections. Obtaining appropriate cultures can be critical
      in making the diagnosis and directing treatment. With the increasing use of
      immunosuppressive agents, including TNF alpha inhibitors, it is likely that there
      will be an increase in the number of mycobacterial infections complicating
      arthroplasties.

PMID- 18034203
TI  - Thalidomide has both anti-inflammatory and regulatory effects in Behcet's
      disease.
AB  - Thalidomide is shown to be an effective treatment for mucocutaneous symptoms of
      Behcet's disease (BD). In this study, the effects of thalidomide on peripheral
      blood mononuclear cells were investigated ex vivo. In an open prospective study,
      ten patients were given 200 mg/day thalidomide for 12 weeks and cluster of
      differentiation 4 (CD4), CD8, CD11a, CD11b, CD16, CD18, CD28, CD44, CD45RO,
      CD45RA, CD56, CD120a and gammadelta+ T cells were analysed with flow cytometry at
      0, 3, 7, 30 and 90 days. Two patients were excluded from the analysis for attacks
      of uveitis within the first 2 weeks. At day 7, tumour necrosis factor-alpha (TNF
      alpha) receptor+ (CD120a; 12% vs 5%), CD8/CD11b+ (12% vs 6%) and CD16/CD56+ (16%
      vs 9%) cells decreased in BD patients compared to day 0. On the other hand,
      CD4+CD45RO+ T cells (24% vs 34%) at day 30 and gammadelta+ T cells (11% vs 21%)
      at day 90 increased after treatment. These results suggest that thalidomide tends
      to decrease TNF-alpha receptor levels, CD8/CD11b+ T cells and natural killer
      cells in early treatment and increases CD4+CD45RO+ memory T and gammadelta+ T
      cells later in BD.

PMID- 18034204
TI  - Observational study on HIV-infected subjects failing HAART receiving tenofovir
      plus didanosine as NRTI backbone.
AB  - We evaluated the efficacy of tenofovir (TDF) - and didanosine (ddI)-containing
      backbones in HIV-infected experienced subjects. We included in the study 245
      subjects who started a TDF/ddI-containing HAART with HIV-RNA > 3 log(10) cp/ml
      and an available genotypic resistance test at baseline. At baseline, median CD4
      counts and HIV-RNA were 278 cell/mmc and 4.32 log(10) cp/ml, respectively.
      Seventy-four subjects (30.2%) discontinued TDF and/or ddI, 23 of them for drug
      related toxicities or intolerance. One-hundred and twenty-six (51.4%) subjects
      achieved virologic success (HIV-RNA < 50 copies/ml in two consecutive
      determinations) in a median time of 6.1 months; higher HIV-RNA levels (HR: 0.66,
      95% CI: 0.54- 0.79, p < 0.001 for each additional log(10) copies/ml), and the
      total number of mutations either for PI and NNRTI at baseline (HR: 0.87, 95% CI:
      0.81-0.92, p < 0.001 for each additional mutation) were both predictors of
      virologic success. M184V was marginally associated with virologic success (HR:
      1.34, 95% CI: 0.94-1.90, p = 0.10 vs no M184V), whilst the number of TAMs was not
      associated. One-hundred-thirty-three (54.3%) subjects achieved immunologic
      success (increase of > or = 100 cells/mm(3) from baseline) in a median time of
      7.5 months; immunologic success was associated with HIV-RNA levels at baseline
      (HR: 0.91, 95% CI: 0.79-0.98, p = 0.04 for each additional log(10) copies/ml),
      the total number of mutations either for PI or NNRTI (HR: 0.91, 95% CI: 0.85
      0.98, p = 0.01 for each additional mutation) and CD4 count at baseline (HR: 1.11,
      95% CI: 1.00-1.23, p = 0.05 for each additional 100 cells/mm(3)). Results
      obtained by the on-treatment analyses were comparable. In our study, HAART
      containing TDF/ddI seem associated with a virologic and immunologic response,
      when such regimens are chosen according to a genotypic resistance test.

PMID- 18034205
TI  - Bacterial meningitis in an urban area: etiologic study and prognostic factors.
AB  - OBJECTIVES: The study of clinical features, diagnostic methods and prognostic
      factors of bacterial meningitis, in an urban area. PATIENTS AND METHODS: All
      patients admitted between June 2001 and July 2004 in the emergency departments of
      a few hospitals, with the diagnosis of bacterial meningitis were included. CSF
      and blood cultures were performed in every case. Phenotypic characterization of
      strains of Streptococcus pneumoniae and Neisseria meningitidis identified by
      culture were performed. In order to detect the three most common agents it was
      done a PCR assay in culture negative CSF samples. RESULTS: Bacterial meningitis
      was diagnosed in 201 patients. Etiologic definition was based on culture in 142
      patients (70.6%), done by CSF PCR assay in 33 (16.4%) other patients and
      exclusively by latex agglutination test results in two cases. Thus, an etiologic
      diagnosis was established in 177 (88%) cases. Antigenic characterization showed a
      slight prevalence of N. meningitidis phenotype C:2b:P1; the S. pneumoniae
      serotype characterization showed that 43.8% of identified serotypes are not
      included in any of the available vaccines. Eighteen patients died (8.9%). The
      statistic analysis found that factors associated with an adverse outcome were age
      older than 50 years (OR 7.07; IC 95% 1.1-27.4), the presence of comorbidities (OR
      3.3; IC 95% 1.1-9.6) and the occurrence of systemic complications (OR 5.8; IC 95%
      2.1-16.0). CONCLUSIONS: This epidemiologic pattern is similar to that found in
      other countries after the introduction of Haemophilus influenzae b conjugated
      vaccine. The association of culture and noncultural methods of diagnosis had a
      better performance in defining the etiology. Comparing to other series, in
      patients mortality rate was lower (8.9%) than usually referred to, being
      considered unfavourable prognostic factors the age more than 50 years, the
      presence of comorbidities and of systemic complications.

PMID- 18034206
TI  - Congenital pyelectasis in children born from mothers on tenofovir containing
      therapy during pregnancy: report of two cases.

PMID- 18034207
TI  - Neuromuscular and central nervous system manifestations of Clostridium
      perfringens infections.
AB  - Infections with Clostridium perfringens usually manifest locally or spread to
      sepsis with multiorgan involvement, hemolysis or septic shock. Central nervous
      system (CNS) manifestations are rare and most frequently comprise meningitis with
      or without pneumencephalon, encephalitis, plexitis, cerebral abscess, or subdural
      empyema. The course of CNS affections is usually foudroyant and the outcome
      fatal. Neuromuscular manifestations of C. perfringens infections are much more
      frequent than CNS manifestations and comprise myonecrosis (gas gangrene),
      rhabdomyolysis, myositis, fasciitis, affection of the neuromuscular transmission,
      or affection of the peripheral nerves. C. perfringens infections usually start
      from the site of a recent surgical wound or trauma, a gastrointestinal or
      urogenital problem, or occur in association with malignancy. In quite a number of
      cases the source of origin remains speculative. Treatment of choice is surgical
      debridement of the infectious focus with radical removal of all necrotic tissue,
      resection of the corresponding lymphatics in addition to antibiotic therapy with
      penicillin G, aminoglycosides, or clindamycin or hyperbaric oxygenation. Despite
      these therapeutic options, the prognosis of CNS and neuromuscular involvement in
      an infection with C. perfringens is still poor. Only focal infections or
      clostridial brain abscesses may eventually have a more favorable outcome, if
      surgery and antibiotics are instantly provided. Generally, early recognition of
      the infectious agent is of paramount importance to prevent from spreading and the
      development of severe hemolysis, septic shock, or death.

PMID- 18034208
TI  - Dissemination of Pseudomonas aeruginosa producing SPM-1-like and IMP-1-like
      metallo-beta-lactamases in hospitals from southern Brazil.
AB  - BACKGROUND: Metallo-beta-lactamase (MBL) is an emerging resistance mechanism
      among Pseudomonas aeruginosa. The prevalence of this mechanism is particularly
      high in Latin America. We aimed to describe the prevalence and molecular
      characteristics of SPM-1-like, IMP-1-like and VIM type MBLs among ceftazidime
      and/or imipenem-resistant nosocomial P. aeruginosa isolates. METHODS: Pseudomonas
      aeruginosa isolates resistant to ceftazidime and/or imipenem recovered from
      hospitalized patients from two teaching hospitals from Porto Alegre, Brazil, were
      prospectively selected. Isolates were tested for MBL production using two
      phenotypic screening tests. Those isolates with positive results were further
      tested for the presence of MBL genes (SPM-1-like, IMP-1-like and VIM type) and
      submitted to molecular typing. RESULTS: A total of 92 isolates were analyzed and
      33 (35.9%) were presumptively MBL producers by phenotypic tests. The SPM-1-like
      gene was found in 18 isolates and IMP-1-like in 5 isolates. In ten isolates the
      MBL type could not be identified. Three IMP-1-like isolates were susceptible to
      imipenem. SPM-1-like isolates comprised a single clone, and IMP-1-like isolates
      another single clone. CONCLUSION: The prevalence of MBL production among
      ceftazidime-resistant P. aeruginosa isolates is relatively high in both
      hospitals. Infection control measures have been challenged and further
      improvements in such measures are required to prevent dissemination of these
      isolates among hospitals. This is the first report of IMP-1-like MBLs in P.
      aeruginosa in southern Brazil.

PMID- 18034209
TI  - Typing of vancomycin-resistant Enterococcus faecium strains in a cohort of
      patients in an Italian intensive care Unit.
AB  - BACKGROUND: Vancomycin-resistant enterococci (VRE) have become a major cause of
      nosocomial infections. The increase of vancomycin-resistant Enterococcus faecium
      (VR-Efm) in an intensive care unit (ICU) of an Italian university hospital from
      2003 through 2004, led us to evaluate the phenotypic and genetic features of
      these strains. The prevalence of different bacterial species in this ICU is
      described. The antibiotic resistance profiles of VR-Efm strains, their van
      genotype and pulsed-field gel electrophoresis (PFGE) profiles were also analyzed.
      MATERIALS AND METHODS: From January 2003 to December 2004, VR-Efm strains were
      collected from several biological samples. Bacteria were identified using
      standard biochemical reactions and automated systems. Antibiotic susceptibility
      was evaluated by disk diffusion and microdilution methods. Resistance to
      glycopeptides was confirmed by the E test. Vancomycin-resistant genotypes (vanA,
      vanB) were identified by PCR. Strains were typed by PFGE. RESULTS: Fifty E.
      faecium strains were isolated from a total of 700 patients. Of these, 26 were
      vancomycin-resistant and were isolated from 26 different patients. We also found
      one strain with resistance to linezolid. The vanA genotype was identified in
      20/26 strains and vanB in the remaining strains. A major pulsed-field cluster
      ("A") was identified. In this cluster, 14 strains were identified (A1-A14) and 25
      out of 26 VR-Efm belonged to it. Only one strain showed a different pattern
      (strain type "B"). All isolates with the vanA genotype belonged to cluster "A",
      therefore five out of six isolates with the vanB genotype belonged to cluster A.
      The only strain with type B pattern was the vanB genotype. CONCLUSIONS: Isolation
      of VR-Efm was very frequent (52%) in our cohort of patients and the vanA genotype
      was the most frequent (77%). We found 25 out of 26 VR-E. faecium strains to be
      epidemiologically related by PFGE (cluster A). Strains with distinct genotypes
      shared closely related PFGE profiles. The occurrence of one major cluster among
      patients of a single unit indicated intra-facility VRE transmission.

PMID- 18034210
TI  - Hospitalization rates for complicated and uncomplicated chickenpox in a poorly
      vaccined pediatric population.
AB  - BACKGROUND: A retrospective study was conducted to provide epidemiological data
      on hospitalization for complicated and uncomplicated chickenpox in a pediatric
      population. METHODS: The study analyzed hospitalization cases for chickenpox,
      among all the 31 Tuscan hospitals, during the period 1997-2003. RESULTS:
      Globally, 650 cases were recorded (306 = 47.07% for uncomplicated and 344 =
      52.92% for complicated chickenpox). Total hospitalization rate was 22.66 per
      100,000 living Tuscan children and 11.52 per 1,000 notified chickenpox cases.
      Hospitalization rates for complicated chickenpox were 12.00 per 100,000 living
      children and 6.09 per 1,000 notified cases. Notably, significantly increased
      hospitalization rates for complicated chickenpox were evidenced over years (p =
      0.011 per 100,000 living children and p = 0.001 per 1,000 notified cases), due to
      the increased proportion of neurological (p = 0.043 per 100,000 living children
      and p = 0.025 per 1,000 notified cases) and respiratory (p = 0.021 per 100,000
      living children and p = 0.008 per 1,000 notified cases) complications, whereas
      hospitalization rates for other complications as well as for uncomplicated
      chickenpox remained constant (p = 0.25 per 100,000 living children and p = 0.09
      per 1,000 notified cases). CONCLUSIONS: Chickenpox complications, requiring
      hospitalization, occurred at a substantial rate in our pediatric population. In
      particular, increasing hospitalization rates for neurological and respiratory
      complications were evidenced over the study period. Our epidemiological data may
      provide additional information while planning a vaccination strategy for Italy.

PMID- 18034211
TI  - A randomized study of sequential intravenous/oral moxifloxacin in comparison to
      sequential intravenous ceftriaxone/oral cefuroxime axetil in patients with
      hospital-acquired pneumonia.
AB  - BACKGROUND: Empiric treatment of hospital-acquired pneumonia (HAP) should be
      focused on the suspected pathogens. We evaluated the efficacy and safety of
      moxifloxacin vs ceftriaxone in patients with HAP without risk of infections with
      Pseudomonas aeruginosa and other non-fermentative Gram-negative bacteria.
      PATIENTS AND METHODS: We performed a prospective, randomized, non-blind,
      multicentric and multinational study to compare the efficacy and safety of
      moxifloxacin 400 mg IV once daily followed by oral moxifloxacin 400 mg once daily
      to ceftriaxone 2 g IV once daily followed by oral cefuroxime axetil 500 mg twice
      daily to treat mild-to-moderate HAP in adult patients requiring initial
      parenteral therapy. The primary efficacy variable was clinical response 7-10 days
      after the end of a 7-14-day treatment period, secondary endpoints included
      clinical and bacteriologic response at different intervals for up to 31 days
      after treatment. The trial was terminated prematurely due to slow patient
      recruitment. RESULTS: A total of 161 subjects (87 men, 74 women) between 18 and
      95 years of age were enrolled, 120 of whom were eligible for per protocol
      efficacy analyses (60 each in the moxifloxacin and the comparator groups).
      Clinical success rates were 87% for moxifloxacin and 83% for the comparator [95%
      CI (-9.77 to 15.96%)]. The results for secondary endpoints were comparable
      between groups. Both treatments were safe and well tolerated. CONCLUSION:
      Moxifloxacin IV/oral can be considered as a possible alternative for the
      antibiotic treatment of patients with mild-to-moderate nosocomial pneumonia
      without risk factors for highly resistant microorganisms.

PMID- 18034212
TI  - Long-sustaining response in a patient with non-resectable, distant recurrence of
      glioblastoma multiforme treated by interstitial photodynamic therapy using 5-ALA:
      case report.
AB  - Glioblastoma multiforme continues to be a devastating disease despite modest
      improvements in survival achieved at present, and there is an urgent need for
      innovative treatment concepts. Five-aminolevulinic acid (ALA) is a drug which
      induces protoporphyrin IX accumulation in malignant gliomas and has been explored
      for fluorescence-guided resections of these tumors. ALA is also under
      investigation as a photosensitizer. We report a case of a patient with prior left
      frontal glioblastoma multiforme treated by surgery, radiation and chemotherapy,
      who developed a remote lesion in the left insula, which was refractory to
      secondary treatments. In a compassionate use setting she was treated by oral
      application of ALA (20 mg/kg bodyweight), and stereotactic phototherapy achieved
      by positioning four laser diffusors using 3-dimensional irradiation planning, and
      a 633 nm diode laser. The lesion disappeared 24 h after therapy. Circumferential
      contrast enhancement was observed at 72 h, which disappeared in the course of
      subsequent months. Edema resolved completely. The patient is still free of
      recurrence 56 months after treatment, demonstrating an impressive and long
      lasting response to this novel mode of therapy.

PMID- 18034213
TI  - Macular retinal detachment associated with peripapillary detachment in pathologic
      myopia.
AB  - PURPOSE: A peripapillary detachment in pathologic myopia (PDPM) appears as a
      yellowish-orange lesion around the optic disc in highly myopic eyes. We report a
      case in which a macular retinal detachment (RD) accompanied a PDPM. METHOD: A
      case report was used in this study. RESULTS: The right eye in a 48-year-old man
      showed a macular RD and a PDPM. Fluorescein fundus angiography showed no dye
      leakage, suggestive of an optic pit within the optic disc. Optical coherence
      tomography (OCT) examination revealed that there was a full-thickness tissue
      defect in the retina overlying PDPM, the vitreous cavity was connected to PDPM
      through this defect, and the PDPM was continuous with the RD through the
      subretinal path at the conus area. CONCLUSIONS: These findings suggest that this
      eye had a macular RD associated with a PDPM, and eyes with a PDPM might be at
      risk of developing macular RD.

PMID- 18034214
TI  - Clinical and optical coherence tomographic findings and outcome of treatment in
      patients with presumed tuberculous uveitis.
AB  - PURPOSE: To define the clinical characteristics and optical coherence tomographic
      (OCT) features, and to assess the outcome of treatment, in patients with presumed
      tuberculous uveitis (PTU). METHODS: All patients diagnosed with PTU at King
      Abdulaziz University Hospital between January 1998 and May 2006 were reviewed.
      The diagnosis was made when findings were consistent with possible intraocular
      tuberculosis with no other cause of uveitis suggested by history, symptoms, or
      ancillary testing, strongly positive tuberculin skin-test results, and response
      to antituberculous therapy. RESULTS: Fifty-one patients (73 eyes) were
      identified. There were 34 males (66.7%) and 17 females (33.3%) with a mean age of
      40.1+/-11.0 years (range 16-68 years). Fifty-eight eyes (79.5%) had panuveitis
      and 15 eyes (20.5%) had posterior uveitis at presentation. Clinical
      manifestations included vitritis (71.2%), macular edema (63%), retinal
      periphlebitis (35.6%), multifocal choroiditis (20.5%), and granulomatous anterior
      uveitis (17.9%). All patients received antituberculous therapy and systemic
      corticosteroids. After a mean follow-up of 18.9+/-21.9 months (range 6-96
      months), all eyes showed resolution of inflammation, with no recurrences,
      associated with significant improvement in visual acuity (VA) (P=0.007). There
      was a significant positive correlation between initial and final VAs (r=0.7856,
      P<0.001). Thirty-one eyes with macular edema were examined at baseline and at
      follow-up with OCT. There were three patterns of macular edema: diffuse (DME)
      (28.5%), cystoid (29%), and serous retinal detachment (45.2%). Initial VA of
      20/40 or better was significantly associated with central macular thickness (CMT)
      of 300 microm or less (P=0.0065) and DME (0.0484). At final follow-up, there was
      a significant reduction in CMT (P<0.001) associated with a significant
      improvement in VA (P=0.0091). CONCLUSIONS: Antituberculous therapy combined with
      systemic corticosteroids leads to resolution of inflammation and elimination of
      recurrences of PTU. OCT is useful in monitoring the efficacy of treatment in
      patients with macular edema.

PMID- 18034215
TI  - European principles of management of common headache disorders in primary care.

PMID- 18034216
TI  - Is the evolutionary history of the O-type P element in the saltans and willistoni
      groups of Drosophila similar to that of the canonical P element?
AB  - We studied the occurrence of O-type P elements in at least one species of each
      subgroup of the saltans group, in order to better understand the phylogenetic
      relationships among the elements within the saltans group and with those of
      species belonging to the willistoni group. We found that the O-type subfamily has
      a patchy distribution within the saltans group (it does not occur in D.
      neocordata and D. emarginata), low sequence divergence among species of the
      saltans group as well as in relation to species of the willistoni group, a lower
      rate of synonymous substitution for coding sequences compared to Adh, and
      phylogenetic incongruities. These findings suggest that the evolutionary history
      of the O-type subfamily within the saltans and willistoni groups follows the same
      model proposed for the canonical subfamily of P elements, i.e., events of
      horizontal transfer between species of the saltans and willistoni groups.

PMID- 18034217
TI  - Reentrant isotropic-calamitic nematic phase transition in potassium laurate
      decanol- D2O mixtures.
AB  - The phase diagram is an interesting field of research, particularly in lyotropic
      liquid crystals (LLC). In this way, one of the most important phase diagrams of
      this LLC system was reported by Yu and Saupe. Two uniaxial (calamitic--N(C) and
      discotic--N(D)) and one biaxial nematic (N(B)) phases were determined by these
      authors. Furthermore, in this phase diagram the classical isotropic phase (I was
      observed at high temperature as well as a reentrant isotropic phase (I(RE)) which
      takes place at lower temperature. Later, this phase diagram was also studied by
      several authors and in all cases the I(RE)-N(C)-I phase transitions were not
      observed. In this work, we present a study of this phase diagram through digital
      image processing and refractometry optical techniques. The occurrence of these
      phase transitions is investigated and characterized. In addition, the order
      parameter is obtained based on the Vuks hypothesis from a particular point, in
      the range of the N(C) phase, where the absolute value of the optical
      birefringence (Deltan is maximum.

PMID- 18034218
TI  - Surface glass transition in bimodal polystyrene mixtures.
AB  - Using the cluster-embedding method of V. Zaporojchenko et al. (Macromolecules 34,
      1125 (2000)), we measured the glass transition temperature T (g) at the
      polystyrene/vacuum interface of bimodal mixtures of monodisperse polystyrenes of
      3.5k and 1000k. Embedding of approximately 1 nm Au clusters was monitored in situ
      by X-ray photoelectron spectroscopy (XPS). The clusters were formed by
      evaporation of Au onto the polymer surface. Only one glass transition was
      observed in the mixtures. The surface glass transition temperatures are
      correlated to but are below the bulk values of the mixtures and obey the Gordon
      Taylor equation. The results suggest that the earlier reported molecular-weight
      dependence of the surface glass transition is not due to segregation of short
      chains to the surface.

PMID- 18034219
TI  - [Glycemic control in sepsis and septic shock: friend or foe?].
AB  - INTRODUCTION: Intensive care patients commonly suffer from hyperglycemia.
      Evidence is growing that strictly maintaining normoglycemia by intensive insulin
      therapy (IIT) ameliorates outcome in these patients. Whether or not this also
      holds true for patients with sepsis and septic shock is the issue of this post
      hoc analysis of the database (2,748 patients) of 2 recent prospective clinical
      trials. MATERIAL AND METHODS: A total of 950 patients suffering from sepsis were
      identified and of these 462 fulfilled the diagnostic criteria of septic shock
      upon admission to the intensive care unit (ICU). Patients were treated by either
      IIT [mean glycemia 5.88 mmol/l (106 mg/dl)] or conventional glucose management
      [mean glycemia 8.44 mmol/l (152 mg/dl)]. RESULTS: Under IIT the mortality of
      patients treated for more than 3 days in the ICU was lowered by 7.6% (p=0.03) in
      septic patients and by 8.7% (p=0.08) in septic shock patients. Polyneuropathy
      occurred less frequently under IIT compared to conventional glucose management
      (sepsis -9.8%, septic shock -14%; p<0.001). The incidence of acute renal failure
      was not affected by either treatment regimen (sepsis -3.3%, septic shock -3.1%;
      p<0.25). Intensive insulin therapy was associated with an increased risk of
      hypoglycemia (sepsis +16.7%, septic shock +18.8; p<0.0001) which did not,
      however, directly affect morbidity nor mortality. CONCLUSIONS: These data suggest
      that IIT improves outcome of patients with sepsis or septic shock. Hypoglycemia
      is a frequent complication, but its clinical relevance remains to be defined.

PMID- 18034220
TI  - [Regenerative medicine in head and neck reconstructive surgery].
AB  - Autologous transplantation is regarded as the gold standard in the treatment of
      congenital or acquired deformities. However, the availability of autologous
      tissue for transplantation is often limited. Regenerative medicine aims to
      activate individuals' own intrinsic regenerative mechanisms and embraces tissue
      engineering, cell/system biology, gene therapy and stem-cell biology. Most
      approaches in tissue engineering are based on the expansion of small autologous
      cell aggregates. Tissue engineering supplemented by isolated and amplified stem
      cells is another very promising option for producing autologous transplants and
      getting over the limited availability. The association of stem cell-based tissue
      engineering and gene therapy allows the creation of regenerative tissue in the
      optimal ambience of regulatory proteins. This leads to great opportunities in the
      transplantation of skin, bones or cartilage. This paper presents the current
      status and the possible benefits, but also the limitations, of regenerative
      medicine in reconstructive surgery of the head and neck.

PMID- 18034221
TI  - [New pharmacological treatment approaches to cardiogenic shock].
AB  - Cardiogenic shock after acute myocardial infarction continues to exhibit a high
      mortality rate. The prognosis can be improved with acute revascularization. Use
      of the intra-aortic balloon pump is also an established treatment concept.
      Administration of catecholamines should be limited as far as possible; monitoring
      hemodynamic parameters based on cardiac power output or cardiac power index can
      be very helpful. New treatment approaches such as the calcium sensitizer
      levosimendan, NO synthase inhibition, complement inhibition, or vasopressin
      therapy have not yet yielded convincing results. Future therapies will likely
      address the anti-inflammatory aspect of cardiogenic shock.

PMID- 18034223
TI  - [Mobile and digital documentation of inpatient treatments : use of personal
      digital assistants in addition with the ClinicCoach(c) software].
AB  - BACKGROUND: Documentation of the individual treatment course is essential from
      medical as well as economic and forensic aspects. With increasing hospital
      computerization the conventional hardcopy form of record keeping is seen to be
      associated with high outlays and restrictiveness. METHODS: Clinicians engaged
      consistently in the development of a personal digital assistant (PDA)-based
      electronic record system (Clinic Coach(c)), which maps the entire course of
      inpatient treatments. The system's effectiveness was reviewed by means of a
      standardized questionnaire and analysis of 8,595 data sets relating to PPR and
      wound findings. RESULTS: In patients undergoing surgery wound findings and PPR
      were documented in 83.6% and in 94.3% respectively. The ClinicCoach(c) System was
      rated more effective than paper-based documentation by 78.4% of the testing
      healthcare workers. CONCLUSION: The combination of PDAs and ClinicCoach(c) is a
      reliable and to clinical routine well adapted system that allows digital
      documentation at the bedside.

PMID- 18034222
TI  - Heme oxygenase and carbon monoxide initiate homeostatic signaling.
AB  - Carbon monoxide (CO), a gaseous second messenger, arises in biological systems
      during the oxidative catabolism of heme by the heme oxygenase (HO) enzymes. Many
      biological functions of HO, such as regulation of vessel tone, smooth muscle cell
      proliferation, neurotransmission, and platelet aggregation, and anti-inflammatory
      and antiapoptotic effects have been attributed to its enzymatic product, CO. How
      can such diverse actions be achieved by a simple diatomic gas; can its protective
      effects be explained via regulation of a common signaling pathway? A number of
      the known signaling effects of CO depend on stimulation of soluble guanylate
      cyclase and/or activation of mitogen-activated protein kinases. The consequences
      of this activation remain unknown but appear to differ depending on cell type and
      circumstances. The majority of studies reporting a protective role of CO focus on
      pathways initiated by the pathological stimulus (e.g., lipopolysaccharide,
      hypoxia, balloon injury, tumor necrosis factor alpha, etc.) and its consequential
      modulation by CO. What has been less studied is the manner in which CO exposure
      alone modulates the molecular machinery of the cell so that a subsequent stress
      stimulus will elicit a homeostatic response as opposed to one that is chaotic and
      disordered. CO potentially interacts with other intracellular hemoprotein
      targets, although little is known about the functional significance of such
      interactions other then the known targets including mitochondrial oxidases,
      oxygen sensors, and nitric oxide synthases. The earliest response of a cell
      exposed to low concentrations of CO is clearly an increase in reactive oxygen
      species formation that we define as oxidative conditioning. This has important
      consequences for inflammation, proliferation, mitochondria biogenesis, and
      apoptosis. Within this review, we will highlight recent research on the molecular
      events underlying the physiologic effects of CO-which lead to cytoprotective
      conditioning.

PMID- 18034224
TI  - Genetic characterization of a new cytoplasmic male sterility system (hau) in
      Brassica juncea and its transfer to B. napus.
AB  - A novel cytoplasmic male sterility (CMS) was identified in Brassica juncea, named
      as hau CMS (00-6-102A). Subsequently, the male sterility was transferred to B.
      napus by interspecific hybridization. The hau CMS has stable male sterility.
      Flowers on the A line are absolutely male sterile, and seeds harvested from the
      line following pollinations with the maintainer gave rise to 100% sterile
      progeny. The anthers in CMS plants are replaced by thickened petal-like
      structures and pollen grains were not detected. In contrast, in other CMS systems
      viz. pol, nap, tour, and ogu, anthers are formed but do not produce viable
      pollen. The sterility of hau CMS initiates at the stage of stamen primordium
      polarization, which is much earlier compared with the other four CMS systems. We
      have successfully transferred hau CMS from B. juncea to B. napus. Restorer lines
      for pol, ogu, nap, and tour CMS systems were found to be ineffective to restore
      fertility in hau CMS. Sixteen out of 40 combinations of mitochondrial
      probe/enzyme used for RFLP analysis distinguished the hau CMS system from the
      other four systems. Among these sixteen combinations, five ones alone could
      distinguish the five CMS systems from each other. The evidence from genetic,
      morphological, cytological and molecular studies confirmed that the hau CMS
      system is a novel CMS system.

PMID- 18034225
TI  - Metabolic programming of offspring by vitamin B12/folate imbalance during
      pregnancy.

PMID- 18034227
TI  - Identification by gene deletion analysis of barS2, a gene involved in the
      biosynthesis of gamma-butyrolactone autoregulator in Streptomyces virginiae.
AB  - Virginiae butanolide (VB) is a member of the gamma-butyrolactone autoregulators
      and triggers the production of streptogramin antibiotics virginiamycin M1 and S
      in Streptomyces virginiae. A VB biosynthetic gene (barS2) was localized in a 10
      kb regulatory island which controls the virginiamycin biosynthesis/resistance of
      S. virginiae, and analyzed by gene disruption/complementation. The barS2 gene is
      flanked by barS1, another VB biosynthetic gene catalyzing stereospecific
      reduction of an A-factor-type precursor into a VB-type compound, and barX
      encoding a pleiotropic regulator for virginiamycin biosynthesis. The deduced
      product of barS2 possessed moderate similarity to a putative dehydrogenase of
      Streptomyces venezuelae, encoded by jadW2 located in similar gene arrangement to
      that in the regulatory island of S. virginiae. A barS2-disruptant (strain IC152),
      created by means of homologous recombination, showed no differences in growth in
      liquid medium or morphology on solid medium compared to a wild-type strain,
      suggesting that BarS2 does not play any role in primary metabolism or
      morphological differentiation of S. virginiae. In contrast, no initiation of
      virginiamycin production or VB production was detected with the strain IC152
      until 18 h of cultivation, at which time full production of virginiamycin occurs
      in the wild-type strain. The delayed virginiamycin production of the strain IC152
      was fully restored to the level of the wild-type strain either by the exogenous
      addition of VB or by complementation of the intact barS2 gene, indicating that
      the lack of VB production at the initiation phase of virginiamycin production is
      the sole reason for the defect of virginiamycin production, and the barS2 gene is
      of primary importance for VB biosynthesis in S. virginiae.

PMID- 18034226
TI  - Diabetic polyneuropathy is associated with respiratory muscle impairment in type
      2 diabetes.
AB  - AIMS/HYPOTHESIS: Diabetes has a major negative effect on intensive care unit
      outcome. This has been partly attributed to impaired respiratory neuromuscular
      function. However, data on respiratory neuromuscular involvement in diabetes are
      lacking. This study therefore aimed to assess respiratory neuromuscular function
      related to diabetic polyneuropathy in patients with type 2 diabetes. METHODS:
      Respiratory neuromuscular function was assessed by the use of volitional tests
      and twitch mouth (TwPmo) and twitch transdiaphragmatic (TwPdi) pressures during
      non-volitional bilateral anterior magnetic phrenic nerve stimulation in 21 male
      type 2 diabetic patients without pulmonary disease and in 23 healthy, well
      matched controls (forced expiratory volume in 1 s 103 +/- 11 vs 103 +/- 12%
      predicted; p = 0.9). RESULTS: Both volitionally assessed maximal inspiratory and
      expiratory mouth pressures, and sniff nasal and transdiaphragmatic pressures were
      comparable between diabetic patients and controls (p > 0.1 for all). TwPmo was
      reduced in diabetic patients compared with controls (1.3 +/- 0.5 vs 1.0 +/- 0.4
      kPa; p = 0.04), while TwPdi was comparable (1.7 +/- 0.5 vs 1.6 +/- 0.7 kPa; p =
      0.6). Following subgroup analysis, patients with no or mild polyneuropathy (n =
      10) as assessed by neurological disability scoring had normal respiratory
      neuromuscular function, whereas patients with moderate or severe polyneuropathy
      (n = 11) presented with markedly impaired respiratory neuromuscular function as
      indicated by TwPmo (1.3 +/- 0.4 vs 0.8 +/- 0.3 kPa; p = 0.01) and TwPdi (1.9 +/-
      0.6 vs 1.1 +/- 0.4 kPa; p < 0.01). CONCLUSIONS/INTERPRETATION: With regard to
      volitional tests, diabetes does not affect respiratory neuromuscular function. In
      contrast, the application of non-volitional phrenic nerve stimulation provides
      strong evidence that diabetic polyneuropathy, as simply assessed by neurological
      disability scoring, is associated with substantially impaired respiratory
      neuromuscular function in type 2 diabetic patients.

PMID- 18034228
TI  - Occurrence and antagonistic potential of Stenotrophomonas strains isolated from
      deep-sea invertebrates.
AB  - Stenotrophomonas maltophilia is known to be of significance as opportunistic
      pathogen as well as a source of biocontrol and bioremediation activities. S.
      maltophilia strains have been isolated from rhizospheres, soil, clinical
      material, aquatic habitats, but little is known about Stenotrophomonas strains
      recovered from marine environments. During a survey of the biodiversity of
      Pseudomonas-like bacteria associated with deep-sea invertebrates six
      Stenotrophomonas strains were isolated from sponge, sea urchin, and ophiura
      specimens collected from differing Pacific areas, including the Philippine Sea,
      the Fiji Sea and the Bering Sea. 16S rRNA gene sequence analysis confirmed an
      assignment of marine isolates to the genus Stenotrophomonas as it placed four
      strains into the S. maltophilia CIP 60.77T cluster and two related to the S.
      rhizophila DSM 14405T. Together with a number of common characteristics typical
      of S. maltophilia and S. rhizophila marine isolates exhibited differences in
      pigmentation, a NaCl tolerance, a range of temperatures, which supported their
      growth, substrate utilization pattern, and antibiotics resistance. Strains
      displayed hemolytic and remarkable inhibitory activity against a number of fungal
      cultures and Gram-positive microorganisms, but very weak or none against Candida
      albicans. This is the first report on isolation, taxonomic characterization and
      antimicrobial activity of Stenotrophomonas strains isolated from deep-sea
      invertebrates.

PMID- 18034229
TI  - Genotypic and phenotypic analysis of strains assigned to the widespread
      cyanobacterial morphospecies Phormidium autumnale (Oscillatoriales).
AB  - In this study, ten cyanobacterial strains assigned to the oscillatorian species
      Phormidium autumnale have been characterized using a polyphasic approach by
      comparing phenotypic and molecular characteristics. The phenotypic analysis dealt
      with cell and filament morphology, ultrastructure, and pigment content. The
      molecular phylogenetic analyses were based on sequences of the 16S rRNA gene and
      the adjacent intergenic transcribed spacer (ITS). The strains were quite
      homogenous in their morphologic features. Their thylakoids showed a stacked or
      fascicular pattern. Some, but not all strains contained phycoerythrin. Only one
      strain (P. autumnale UTCC 476) deviated significantly in its phenotype by lacking
      a calyptra. In neighbour-joining and maximum Parsimony trees most 16S rRNA
      sequences were located on a single well-defined branch, which, however, also
      harboured sequences assigned to other cyanobacterial genera. Two strains (P.
      autumnale UTCC 476 and P. autumnale UTEX 1580) were found on distant branches.
      The presence of phycoerythrin was not correlated with the strains' position in
      the phylogenetic trees. Our results reconfirm that the morphospecies P. autumnale
      and the Phormidium group in general are not phylogenetically coherent and require
      revision. However, as indicated by sequence similarities most of the strains
      assigned to P. autumnale except P. autumnale UTCC 476 and P. autumnale UTEX 1580
      are phylogenetically related and might belong to a single genus.

PMID- 18034230
TI  - Therapeutic receptor targets for lower urinary tract dysfunction.
AB  - The functions of the lower urinary tract, to store and periodically release
      urine, are dependent on the activity of smooth and striated muscles in the
      bladder, urethra, and external urethral sphincter. During urine storage, the
      outlet is closed, and the bladder smooth muscle is quiescent. When bladder volume
      reaches the micturition threshold, activation of a micturition center in the
      dorsolateral pons (the pontine micturition center) induces a bladder contraction
      and a reciprocal relaxation of the urethra, leading to bladder emptying. During
      voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input
      (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to
      the urethra. These peripheral systems are integrated by excitatory and inhibitory
      regulation at the levels of the spinal cord and the brain. Injury or diseases of
      the nervous system, as well as drugs and disorders of the peripheral organs, can
      produce lower urinary tract dysfunction. In the overactive bladder (OAB)
      condition, therapeutic targets for facilitation of urine storage can be found at
      the levels of the urothelium, detrusor muscles, autonomic and afferent pathways,
      spinal cord, and brain. There is increasing evidence showing that the urothelium
      has specialized sensory and signaling properties including: (1) expression of
      nicotinic, muscarinic, tachykinin, adrenergic, bradykinin, and transient receptor
      potential (TRP) receptors, (2) close physical association with afferent nerves,
      and (3) ability to release chemical molecules such as adenosine triphosphate
      (ATP), acetylcholine, and nitric oxide. Increased expression and/or sensitivity
      of these urothelial-sensory molecules that lead to afferent sensitization have
      been documented as possible pathogenesis of OAB. Targeting afferent pathways
      and/or bladder smooth muscles by modulating activity of ligand receptors (e.g.,
      neurokinin, ATP, or beta3-adrenergic receptors) and ion channels (e.g., TRPV1 or
      K) could be effective to suppress OAB. In the stress urinary incontinence
      condition, pharmacotherapies targeting the neurally mediated urethral continence
      reflex during stress conditions such as sneezing or coughing could be effective
      for increasing the outlet resistance. Therapeutic targets include adrenergic and
      serotonergic receptors in the spinal cord as well as adrenergic receptors at the
      urethral sphincter, which can enhance urethral reflex activity during stress
      conditions and increase baseline urethral pressure, respectively.

PMID- 18034232
TI  - Miniaturisation of analytical steps: necessity and snobbism.

PMID- 18034231
TI  - Improvement of contextual memory by S 24795 in aged mice: comparison with
      memantine.
AB  - RESULTS: In comparison with 5-month-old mice, 18- to 19-month-old mice exhibited
      a severe and specific memory impairment in a contextual serial discrimination
      (CSD) task involving the learning and remembering of two successive spatial
      discriminations carried out on two distinct floors. This impairment was specific,
      as spatial memory, simultaneously tested on a simple discrimination (SD) task,
      was not affected in these aged mice. This deficit was completely reversed by 9
      day per os administration of S 24795, a partial agonist of alpha 7 nicotinic
      receptors, at either 0.3 or 1.0 mg/kg. Memantine, an NMDA receptor antagonist,
      also had a memory-enhancing effect at a dose of 3.0 mg/kg, but not at 0.3 mg/kg.
      CONCLUSIONS: The memory-enhancing effect of S 24795 was due to a strong
      enhancement of contextual memory as indicated by a decrease in interference rate,
      whereas memantine enhanced spatial/semantic memory. S 24795 was more effective
      than memantine and also appears to be more specific to flexible forms of memory,
      one of the first cognitive domains (i.e. episodic memory) affected in Alzheimer's
      disease.

PMID- 18034233
TI  - Magnetic resonance imaging of the normal pituitary gland using ultrashort TE
      (UTE) pulse sequences (REV 1.0).
AB  - INTRODUCTION: The purpose of this study was to examine the normal pituitary gland
      in male subjects with ultrashort echo time (TE) pulse sequences, describe its
      appearance and measure its signal intensity before and after contrast
      enhancement. METHODS: Eleven male volunteers (mean age 57.1 years; range 36-81
      years) were examined with a fat-suppressed ultrashort TE (=0.08 ms) pulse
      sequence. The studies were repeated after the administration of intravenous
      gadodiamide. The MR scans were examined for gland morphology and signal intensity
      before and after enhancement. Endocrinological evaluation included baseline
      pituitary function tests and a glucagon stimulatory test to assess pituitary
      cortisol and growth hormone reserve. RESULTS: High signal intensity was observed
      in the anterior pituitary relative to the brain in nine of the 11 subjects. These
      regions involved the whole of the anterior pituitary in three subjects, were
      localised to one side in two examples and were seen inferiorly in three subjects.
      Signal intensities relative to the brain increased with age, with a peak around
      the sixth or seventh decade and decreasing thereafter. Overall, the pituitary
      function tests were considered to be within normal limits and did not correlate
      with pituitary gland signal intensity. CONCLUSION: The anterior pituitary shows
      increased signal intensity in normal subjects when examined with T(1)-weighted
      ultrashort TE pulse sequences. The cause of this increased intensity is unknown,
      but fibrosis and iron deposition are possible candidates. The variation in signal
      intensity with age followed the temporal pattern of iron content observed at post
      mortem. No relationship with endocrine status was observed.

PMID- 18034234
TI  - Magnetic resonance neurography in children with birth-related brachial plexus
      injury.
AB  - BACKGROUND: Magnetic resonance neurography (MRN) enables visualization of
      peripheral nerves. Clinical examination and electrodiagnostic studies have been
      used in the evaluation of birth-related brachial plexus injury. These are limited
      in their demonstration of anatomic detail and severity of injury. OBJECTIVE: We
      investigated the utility of MRN in evaluating birth-related brachial plexus
      injury in pediatric patients, and assessed the degree of correlation between MRN
      findings and physical examination and electromyographic (EMG) findings. MATERIALS
      AND METHODS: The MRN findings in 11 infants (age 2 months to 20 months) with
      birth-related brachial plexus injury were evaluated. A neuroradiologist blinded
      to the EMG and clinical examination findings reviewed the images. Clinical
      history, examination, EMG and operative findings were obtained. RESULTS: All
      infants had abnormal imaging findings on the affected side: seven
      pseudomeningoceles, six neuromas, seven abnormal nerve T2 signal, four nerve root
      enlargement, and two denervation changes. There was greater degree of correlation
      between MRN and physical examination findings (kappa 0.6715, coefficient of
      correlation 0.7110, P < 0.001) than between EMG and physical examination findings
      (kappa 0.5748, coefficient of correlation 0.5883, P = 0.0012). CONCLUSION: MRN in
      brachial plexus trauma enables localization of injured nerves and
      characterization of associated pathology. MRN findings demonstrated a
      statistically significant correlation with physical examination and EMG findings,
      and might be a useful adjunct in treatment planning.

PMID- 18034235
TI  - Functional expression, purification, and characterization of the recombinant
      Baeyer-Villiger monooxygenase MekA from Pseudomonas veronii MEK700.
AB  - For the investigation of the NADPH-dependent Baeyer-Villiger monooxygenase MekA
      from Pseudomonas veronii MEK700, the encoding gene mekA with a C-terminal strep
      tag was cloned and expressed under the control of a L: -rhamnose inducible
      promoter from Escherichia coli. The mekA gene was found by analyzing the
      methylethylketone (MEK) degradation pathway by Onaca et al. J Bacteriol 189:3759
      3767, 2007. Sequence analysis of the corresponding protein, which catalyzes the
      Baeyer-Villiger oxidation of MEK to ethyl acetate, showed two binding sites
      (Rossman-fold motifs) for cofactors NAD(P)H and FAD. Although expression of mekA
      resulted in large amounts of inclusion bodies compared to soluble protein, high
      amounts of purified and active MekA were obtained by affinity chromatography. The
      substrate spectrum of MekA was investigated with purified enzyme and whole cells
      using a variety of aliphatic, aromatic, and cyclic ketones including four chiral
      substrates. The specific activity of MekA with MEK as substrate was determined to
      be 1.1 U/mg protein. K (M) values were determined for MEK and the cofactors NADPH
      and NADH to be 6, 11, and 29 microM, respectively.

PMID- 18034236
TI  - Poly(3-hydroxybutyrate) synthesis from glycerol by a recombinant Escherichia coli
      arcA mutant in fed-batch microaerobic cultures.
AB  - Poly(3-hydroxybutyrate) (PHB) synthesis was analyzed under microaerobic
      conditions in a recombinant Escherichia coli arcA mutant using glycerol as the
      main carbon source. The effect of several additives was assessed in a semi
      synthetic medium by the 'one-factor-at-a-time' technique. Casein amino acids
      (CAS) concentration was an important factor influencing both growth and PHB
      accumulation. Three factors exerting a statistically significant influence on PHB
      synthesis were selected by using a Plackett-Burman screening design [glycerol,
      CAS, and initial cell dry weight (CDW) concentrations] and then optimized through
      a Box-Wilson design. Under such optimized conditions (22.02 g l(-1) glycerol,
      1.78 g l(-1) CAS, and 1.83 g l(-1) inoculum) microaerobic batch cultures gave
      rise to 8.37 g l(-1) CDW and 3.52 g l(-1) PHB in 48 h (PHB content of 42%) in a
      benchtop bioreactor. Further improvements in microaerobic PHB accumulation were
      obtained in fed-batch cultures, in which glycerol was added to maintain its
      concentration above 5 g l(-1). After 60 h, CDW and PHB concentration reached
      21.17 and 10.81 g l(-1), respectively, which results in a PHB content of 51%.
      Microaerobic fed-batch cultures allowed a 2.57-fold increase in volumetric
      productivity when compared with batch cultures.

PMID- 18034237
TI  - Azoreductase and dye detoxification activities of Bacillus velezensis strain AB.
AB  - Azo dyes are known to be a very important and widely used class of toxic and
      carcinogenic compounds. Although lot of research has been carried out for their
      removal from industrial effluents, very little attention is given to changes in
      their toxicity and mutagenicity during the treatment processes. Present
      investigation describes isolation of a Bacillus velezensis culture capable of
      degrading azo dye Direct Red 28 (DR28). Azoreductase enzyme was isolated from it,
      and its molecular weight was found to be 60 kDa. The enzyme required NADH as
      cofactor and was oxygen-insensitive. Toxicity and mutagenicity of the dye during
      biodegradation was monitored by using a battery of carefully selected in vitro
      tests. The culture was found to degrade DR28 to benzidine and 4-aminobiphenyl,
      both of which are potent mutagens. However, on longer incubation, both the
      compounds were degraded further, resulting in reduction in toxicity and
      mutagenicity of the dye. Thus, the culture seems to be a suitable candidate for
      further study for both decolourization and detoxification of azo dyes, resulting
      in their safe disposal.

PMID- 18034239
TI  - Inter-observer reproducibility in reporting on renal drainage in children with
      hydronephrosis: a large collaborative study.
AB  - PURPOSE: The goal of this study was to evaluate the inter-observer
      reproducibility in reporting on renal drainage obtained during (99m)Tc MAG3
      renography in children, when already processed data are offered to the observers.
      METHODS: Because web site facilities were used for communication, 57 observers
      from five continents participated in the study. Twenty-three renograms, including
      furosemide stimulation and posterect postmicturition views, covering various
      patterns of drainage, were submitted to the observers. Images, curves and
      quantitative parameters were provided. Good or almost good drainage, partial
      drainage and poor or no drainage were the three possible responses for each
      kidney. RESULTS: An important bias was observed among the observers, some of them
      more systematically reporting the drainage as being good, while others had a
      general tendency to consider the drainage as poor. This resulted in rather poor
      inter-observer reproducibility, as for more than half of the kidneys, less than
      80% of the observers agreed on one of the three responses. Analysis of the
      individual cases identified some obvious causes of discrepancy: the absence of a
      clear limit between partial and good or almost good drainage, the fact of
      including or neglecting the effect of micturition and change of patient's
      position, the underestimation of drainage in the case of a flat renographic
      curve, and the difficulties of interpretation in the case of a small, not well
      functioning kidney. CONCLUSION: There is an urgent need for better
      standardisation in estimating the quality of drainage.

PMID- 18034240
TI  - 82-Rubidium--the dawn of cardiac PET in Europe?

PMID- 18034241
TI  - FDG uptake by the bone marrow in NSCLC patients is related to TGF-beta but not to
      VEGF or G-CSF serum levels.
AB  - INTRODUCTION: Non small cell lung carcinomas (NSCLC) are known to secrete various
      cytokines such as VEGF (vascular endothelial growth factor), G-CSF (granulocyte
      colony stimulating factor) and TGF-beta (transforming growth factor-beta) that
      may stimulate bone marrow activity. PURPOSE: This study reports on the
      relationship between serum levels of VEGF, G-CSF, TGF-beta and FDG uptake by the
      bone marrow in NSCLC patients. METHODS: Thirty-three patients suffering from
      newly diagnosed NSCLC who were successively referred to undergo an FDG PET scan
      as a part of their routine staging procedure and that did not suffer from bone
      metastases were included in the study. FDG bone marrow activity was determined in
      all patients and related to pre-treatment VEGF, G-CSF and TGF-beta serum levels.
      RESULTS: Mean standardized uptake values (SUV mean) of the bone marrow ranged
      from 0.1 to 2.1 (mean 1.1). G-CSF, VEGF and TGF-beta serum levels ranged from
      13.5 to 110 pg/ml (mean 41.4 pg/ml), from 95 to 3,221 pg/ml (mean 1,111 pg/ml)
      and from 269 to 615 pg/ml (mean 387 pg/ml), respectively. SUV mean values of the
      bone marrow significantly correlated with TGF-beta serum measurements (r = 0.621,
      p < 0.0001), but not with VEGF and G-CSF measurements. CONCLUSION: FDG uptake by
      bone marrow in newly diagnosed NSCLC patients correlates with serum levels of TGF
      beta, but not with VEGF or G-CSF levels.

PMID- 18034242
TI  - Computed-tomography-guided percutaneous radiofrequency thermoablation for the
      treatment of osteoid osteoma-2 to 5 years follow-up.
AB  - The purpose of this study is to evaluate the efficacy of the computed tomography
      (CT)-guided percutaneous radiofrequency thermoablation (PRT) method with a
      minimum of 2 years follow-up. Twenty-eight patients who were followed for more
      than 2 years among 35 patients who underwent CT-guided PRT between April 1999 and
      May 2005 were included in this study. The mean age was 24.5 years (range 7-55
      years) and the mean follow-up period was 40.1 months (range 24-66 months). With a
      radiofrequency electrode, the lesion was heated to 80 degrees C or 90 degrees C
      for 6.5 mins (range 3-9 mins). Clinical success was assessed at the out-patient
      clinic by symptoms and radiographs. Twenty-six patients (90%) experienced a total
      loss of symptoms and additional PRT also relieved the ongoing symptoms in all of
      the recurrent patients. PRT appears to be a safe and effective method for
      treating osteoid osteoma and is also effective in recurrent cases. This treatment
      modality is a minimally invasive procedure and is a good alternative to open
      surgical treatment.

PMID- 18034243
TI  - Tibiofemoral contact areas and pressures in six high flexion knees.
AB  - The tibiofemoral articulating interfaces of six high flexion knee designs were
      examined using a standard testing protocol developed by Harris et al. [J Biomech
      32:951-958 (1999)] to investigate the polyethylene insert contact areas and
      pressures. A load of 3600 N was applied for 10 s at 0, 30, 60, 90, 110, 135 and
      155 degrees of flexion. Contact areas and pressures at the femoral-polyethylene
      insert interface were measured with a I-scan 4000 system. Up to 110 degrees of
      flexion, the VANGUARD RP HI-FLEX showed the highest contact area and lowest
      pressure. At the deep flexion angles, contact area decreased and contact pressure
      increased significantly in all knees. The NexGen series showed a constant contact
      area throughout the various flexion angles. In general, all high flexion knees
      could result in almost point contact in an extremely high range of motion.

PMID- 18034244
TI  - Analysis of single nucleotide polymorphisms in Toll-like receptor 4 shows no
      association with ankylosing spondylitis in a Korean population.
AB  - The role of microbial triggers in the pathogenesis of the ankylosing spondylitis
      (AS) has remained an active area of clinical and basic research but remains
      unresolved. We have recently found evidence of an important role for TLR4 in
      experimental reactive arthritis, raising the question to be addressed whether
      genetic polymorphisms in TLR4 affects susceptibility to AS. Innate immune
      responses to Gram-negative bacteria involve in a central role the binding of
      lipopolysaccharide to TLR4. Two commonly occurring SNPs in the human TLR4 gene
      (Asp299Gly and Thr399Ile) have been shown to be associated with increased risk of
      Gram-negative bacteremia in sepsis patients and with susceptibility to
      inflammatory bowel disease. It remains unresolved whether these SNPs are
      associated with AS and we have addressed this in a relatively genetically
      homogeneous population in Korea. A cohort of 200 Korean AS patients and 197
      ethnically matched controls were studied. All patients were native Koreans with
      AS satisfying the modified New York criteria. Korean controls were examined and
      confirmed to be unaffected by AS. All subjects were genotyped for two functional
      SNPs in the TLR4 gene: Asp299Gly (A/G polymorphism) and TLR-4 (Thr399Ile) (C/T
      polymorphism) The Sequenom MassARRAY system was used for genotyping (Sequenom
      Inc., San Diego, CA, USA). All cases and controls were homozygous for the (A)
      allele for 299 variant and similarly for the 399 variant all cases and controls
      were homozygous for the (C) allele. Genetic-environmental interactions figure
      prominently in current concepts of the pathogenesis of AS. Our findings indicate
      that the polymorphisms in the TLR4 gene cannot be regarded as major contributors
      to AS susceptibility in the Korean population.

PMID- 18034245
TI  - HBV vaccine and dermatomyositis: is there an association?
AB  - The etiology of dermatomyositis is unknown, but immune mechanisms play an
      important role. Several dermatological manifestations have been reported among
      carriers of hepatitis B surface antigen, and after vaccination with the HBV
      vaccine. Almost all the skin reactions described were peculiar skin eruptions
      suggestive of an immune complex reaction. Some authors described the occurrence
      of dermatomyositis after BCG and influenza vaccination. We report a case of a 6
      year-old child, who was vaccinated for hepatitis B virus and developed a flu-like
      disease accompanied by a skin rash, which had the typical features of
      dermatomyositis. The association of vaccination with autoimmunity is discussed.

PMID- 18034246
TI  - Dual-source CT for chest pain assessment.
AB  - Comprehensive CT angiography protocols offering a simultaneous evaluation of
      pulmonary embolism, coronary stenoses and aortic disease are gaining
      attractiveness with recent CT technology. The aim of this study was to assess the
      diagnostic accuracy of a specific dual-source CT protocol for chest pain
      assessment. One hundred nine patients suffering from acute chest pain were
      examined on a dual-source CT scanner with ECG gating at a temporal resolution of
      83 ms using a body-weight-adapted contrast material injection regimen. The images
      were evaluated for the cause of chest pain, and the coronary findings were
      correlated to invasive coronary angiography in 29 patients (27%). The files of
      patients with negative CT examinations were reviewed for further diagnoses.
      Technical limitations were insufficient contrast opacification in six and
      artifacts from respiration in three patients. The most frequent diagnoses were
      coronary stenoses, valvular and myocardial disease, pulmonary embolism, aortic
      aneurysm and dissection. Overall sensitivity for the identification of the cause
      of chest pain was 98%. Correlation to invasive coronary angiography showed 100%
      sensitivity and negative predictive value for coronary stenoses. Dual-source CT
      offers a comprehensive, robust and fast chest pain assessment.

PMID- 18034247
TI  - Phase sensitivity in bat sonar revisited.
AB  - An echolocating bat produces echoes consisting of the convolution of echolocation
      call and the impulse response (IR) of the ensonified object. A crucial question
      in animal sonar is whether bats are able to extract this IR from the echo. The
      bat inner ear generates a frequency representation of call and echo and IR
      extraction in the frequency domain requires accurate analysis of both magnitude
      and phase information. Previous studies investigating the phase sensitivity of
      bats using a jitter paradigm reported a temporal acuity down to 10 ns, suggesting
      perfect sonar phase representation. In a phantom-target playback experiment, we
      investigate the perceptual phase sensitivity of the bat Phyllostomus discolor
      using a novel approach: instead of manipulating IR phase by changing IR delay
      (jitter paradigm), we randomized IR phase and thus lengthened the IR over time,
      leaving the magnitude spectrum unchanged. Our results show that phase
      sensitivity, as reflected in the analysis of signal duration, appears to be much
      lower than phase sensitivity, as reflected in the analysis of signal onset. The
      current data indicate that different temporal aspects of sonar processing are
      encoded with very different temporal resolution and thus an overall claim of
      "phase sensitivity" as such cannot be maintained.

PMID- 18034248
TI  - Successful conservative treatment of traumatic subacute subdural haematomas in
      neonates with haemophilia A.
AB  - PURPOSE: The aim of this report is to enlighten the role of an early diagnosis
      and treatment of haemophilia A during the management of an intracranial
      haemorrhage as well as to discuss the efficiency of a subdural transcoronal
      puncture compared to a craniectomy as surgical treatment of the haematoma.
      BACKGROUND: Haemophilia A constitutes a well-known risk factor for intracranial
      bleeding. However, it has been rarely described as a cause of subdural haematoma
      in neonates. Management of subdural haematomas in haemophilic patients is still
      debated. MATERIALS AND METHODS: We report two cases of infants with subacute
      subdural haematoma. The first of them had a familial history of haemophilia A. In
      the second subject, the diagnosis was obtained during the etiological workup of
      an intracranial haematoma. Both infants were successfully treated with
      transcoronal puncture of the subacute component of the haematoma and factor VIII
      infusion. CONCLUSIONS: Transcranial punctures associated to infusion of factor
      VIII should be considered an alternative surgical option in the management of
      subdural haematomas in neonates with haemophilia A.

PMID- 18034249
TI  - Laparoscopic surgery and its detrimental effects on small and large bowel
      anastomes.

PMID- 18034250
TI  - Incidence, consequences, and risk factors for anastomotic dehiscence after
      colorectal surgery: a prospective monocentric study.
AB  - BACKGROUND: Anastomotic dehiscence is the most severe surgical complication after
      large bowel resection. This study was designed to assess the incidence, to
      observe the consequences, and to identify the risk factors associated with
      anastomotic leakage after colorectal surgery. MATERIALS AND METHODS: All
      procedures involving anastomoses of the colon or the rectum, which were performed
      between November 2002 and February 2006 in a single institution, were
      prospectively entered into a computerized database. RESULTS: One thousand
      eighteen colorectal resections and 811 anastomoses were performed over this 40
      month period. The most frequent procedures were sigmoid (276) and right
      colectomies (217). The overall anastomotic leak rate was 3.8%. The mortality rate
      associated with anastomotic leak was 12.9%. In univariate analysis, the following
      parameters were associated with an increased risk for anastomotic dehiscence: (1)
      ASA score >or= 3 (p = 0.004), (2) prolonged (>3 h) operative time (p = 0.02), (3)
      rectal location of the disease (p < 0.001), (4) and a body mass index > 25 (p =
      0.04). In multivariate analysis, ASA score >or= 3 (OR = 2.5; 95% CI 1.5-4.3, p <
      0.001), operative time > 3 h [OR = 3.0; 95% CI 1.1-8.0, p = 0.02), and rectal
      location of the disease (OR = 3.75; 95% CI 1.5-9.0 (vs left colon), p = 0.003; OR
      = 7.69; 95% CI 2.2-27.3 (vs right colon), p = 0.001] were factors significantly
      associated with a higher risk of anastomotic dehiscence. CONCLUSIONS: Three risk
      factors for anastomotic leak have been identified, one is patient-related (ASA
      score), one is disease-related (rectal location), the third being surgery-related
      (prolonged operative time). These factors should be considered in perioperative
      decision-making regarding defunctioning stoma formation.

PMID- 18034251
TI  - [Early rheumatoid arthritis--rapid help is double help].
AB  - Early diagnosis and therapy of persisting (or chronic) polyarthritis is essential
      for preventing permanent damage. The guidelines of the German Society for
      Rheumatology recommend referral to a rheumatologist 6 weeks (at the latest) after
      symptom onset. DMARD therapy should be initiated within 12 weeks. Even earlier,
      high titer rheumatoid factor, detectable antibodies to CCP, or early erosion,
      constitute firm arguments for initiating DMARD therapy in patients with
      arthritis. At this time point, fast acting combination therapy frequently
      achieves remission or at least low disease activity. Since TNF blockers are not
      commonly available for first line therapy, corticosteroids should accompany DMARD
      initiation. Sufficient capacity in early consultation at arthritis clinics,
      optimized communication with primary care physicians and sensibilisation of the
      entire population are essential to prevent permanent damage in as many patients
      as possible.

PMID- 18034252
TI  - Safety of atlantoaxial fusion using laminar and transarticular screws combined
      with an atlas hook in a patient with unilateral vertebral artery occlusion (case
      report).
AB  - OBJECTIVE AND IMPORTANCE: A disadvantage of transarticular and C2 pedicle screws
      is vertebral artery (VA) injury as a result of screw misplacement. If unilateral
      occlusion of the VA is present, VA injury of the dominant side will cause fatal
      complications as a result of collateral flow insufficiency. Several authors have
      recently reported the usefulness of C2 laminar screws because of their safety on
      VA injury. We used transarticular and C2 laminar screws combined with the atlas
      hook in a patient with C1-2 instability and unilateral VA occlusion, in order to
      reduce the risk of further VA injury. CLINICAL PRESENTATION: A 64-year-old woman
      with rheumatoid atlantoaxial subluxation complained of cervical myelopathy and
      neck pain. Preoperative MR angiography showed a left side VA occlusion.
      TECHNIQUE: The patient underwent atlantoaxial, posterior fusion using a
      transarticular screw on the side of the occlusion and a C2 laminar screw on the
      dominant side combined with a bilateral atlas hook. The transarticular screw was
      inserted using a navigation system and image intensifier, and the laminar screw
      was inserted free hand. Bone grafting from the iliac crest was performed.
      CONCLUSION: Transarticular and C2 laminar screws fixation combined with the atlas
      hook in a patient with unilateral VA occlusion is a useful technique, in order to
      reduce the risk of further VA injury.

PMID- 18034253
TI  - Arthroscopic reconstruction of chronic anteroinferior glenoid defect using an
      autologous tricortical iliac crest bone grafting technique.
AB  - Only a few reports exist on the management of severe anteroinferior glenoid
      defects in case of recurrent shoulder instability most of them including open
      approaches. We describe an all-arthroscopic reconstruction technique of the
      anteroinferior glenoid that includes an autologous iliac crest bone grafting
      using bio-compression screws and a capsulolabral repair using suture anchors.
      This technique recreates the bony and soft-tissue anatomy of the anteroinferior
      glenoid while preserving the integrity of insertion of the subscapularis (SSC)
      tendon.

PMID- 18034254
TI  - Hemi-arthroplasty with supplemental fixation of greater trochanter to treat
      failed hip screws of femoral intertrochanteric fracture.
AB  - INTRODUCTION: Management for failed hip screw after femoral intertrochanteric
      fracture is a challenge for orthopaedic surgeons. The unfavorable factors include
      severe osteoporosis, unstable fracture geometry, improper placement of hip screw,
      and repeated trauma. Except revision fixation of the fractures, arthroplasty may
      be indicated in case of destructed femoral head. In this study, we reported the
      surgical outcomes of patients with concomitant failed hip screws and fractures of
      greater trochanter operated by hemi-arthroplasties. MATERIALS AND METHODS: We
      treated 16 patients of failed hip screws with concomitant fracture of greater
      trochanter surgically by hemi-arthroplasty and cable-grip system from January
      2001 to December 2004. The reattachment of greater trochanter by cable-grip
      system enhanced abductor mechanism to reduce the dislocation rate of hip
      arthroplasty. The hemi-arthroplasties eliminated the pain from the destructed
      femoral head. Partial weight bearing was allowed postoperatively. The patients
      were followed every 6 weeks clinically and radiologically. Full weight bearing
      was not allowed until solid bony union was seen on the plain radiographs.
      RESULTS: Among these 16 patients, all patients achieved solid union of greater
      trochanter except one by 24 weeks postoperatively. No postoperative wound
      infection was found. No dislocation of hemi-arthroplasty occurred during the
      postoperative follow-up. The clinical assessment based on SF-36 questionnaire
      improved from 41.9 to 82.7. CONCLUSION: Hemi-arthroplasty with supplemental
      fixation of greater trochanter is a rational option to treat failed hip screws
      with fracture of greater trochanter in case of destructed femoral head.

PMID- 18034255
TI  - Rapid detection of homozygous mutations in congenital recessive ichthyosis.
AB  - Congenital recessive ichthyoses (CRI) form a remarkably heterogeneous group of
      diseases, resulting from mutations in at least eight distinct genes, six of which
      have been identified so far. In the present study we ascertained two CRI families
      of Iranian and Druze origins. Exploiting the high degree of consanguinity
      characterizing these populations, we typed all family members for microsatellite
      markers spanning the major CRI chromosomal loci and used homozygosity mapping to
      identify candidate genes for subsequent mutational analysis. This strategy led to
      the rapid identification of two novel homozygous CRI-causing mutations in TGM1
      (c.2058delC) and FLJ39501 (p.W521X). The present data demonstrate that the
      molecular analyses of CRI in consanguineous families can be readily completed in
      less than 96 h at relatively low costs.

PMID- 18034256
TI  - Clinical experience of five fetal ovarian cysts: diagnosis and follow-up.
AB  - BACKGROUND: Ovarian cysts are the most frequent type of abdominal tumor, in
      female newborns. The most of the cases resolve spontaneously with no clinical
      significance. However, ovarian cysts often present complications such as torsion.
      CASE: The authors reviewed the pre- and postnatal records and ultrasonograms of
      five fetuses, who were diagnosed with ovarian cysts. No complication was observed
      prenatally. However, one infant 2 months after birth required surgical
      intervention because of cyst torsion. The cysts of the other four infants showed
      complete resolution in a time interval of 3-9 months. CONCLUSION: An ovarian cyst
      is not a life-threatening condition, so they should be just closely monitored pre
      and postnatally until spontaneous resolution. When torsion of the cyst is
      suspected, surgical intervention is necessary.

PMID- 18034257
TI  - Is the audiologic status of professional musicians a reflection of the noise
      exposure in classical orchestral music?
AB  - The sound in classical orchestral music is louder than noise emissions allowed by
      national rules in industry. We wanted to assess the audiologic status of
      professional musicians at different ages of their careers and to look for a
      coherence of declined hearing ability and the sound emissions in order to
      substantiate advices for hearing protection and occupational medicine in
      musicians. Data from questionnaires (anamnestic data on sound exposure in
      profession and leisure times, use of hearing protection, self-evaluation of
      hearing function and hearing deficits), audiometric data and amplitudes of OAE
      were evaluated from 109 professional musicians aged 30-69 years from three major
      German orchestras and from 110 students of an academy of music (aged 11-19
      years). Sound emissions of the whole orchestra and of single
      instruments/instrument groups were measured at the orchestra stages and pits
      during rehearsals and performances. None of the musicians was engaged in noisy
      hobbies and only a few used hearing protectors regularly. More than 50% of the
      musicians had a hearing loss of 15 dB(A) and more. Highest losses were found
      among the strings and the brass players. DPOAE amplitudes coincidently declined
      with the duration of performing music in the orchestras. Professional musicians
      aged older than 60 years had a significantly greater hearing loss at 4 and 6 kHz
      than those aged 30-39 years. Among the strings in one orchestra a dominant
      hearing deficit in the left ears was observed. Musicians need the same health
      care for their hearing as workers in noisy industry. A better education on the
      hearing hazards (use of hearing protectors) as well as sound protection in the
      rehearsal rooms is necessary. Hearing loss in professional musicians should be
      accepted as an occupational disease.

PMID- 18034258
TI  - Randomized study comparing postoperative pain between coblation and bipolar
      scissor tonsillectomy.
AB  - Coblation tonsillectomy has shown promising results with respect to postoperative
      pain when compared with other techniques. Our study was designed to compare this
      technique with bipolar scissor tonsillectomy. Forty adult patients with a history
      of chronic or recurrent tonsillitis referred for standard tonsillectomy were
      recruited and randomized into two groups. Twenty were operated with Coblator and
      20 with bipolar scissors. Exclusion criteria were a history of quinsy, bleeding
      disorder, or any major health problems. All participants completed the study.
      Postoperative pain, return to normal diet, and estimated need for sick leave were
      utilized as parameters. Data on operative time, difficulty of tissue removal, and
      hemostasis were also analyzed. Operative time was longer (P < 0.001) and tissue
      removal as well as hemostasis control were more difficult (P = 0.005, P = 0.013)
      with Coblator than with bipolar scissors. Participants in Coblator group assessed
      higher pain scores 1 and 3 h postoperatively (P = 0.044, P = 0.036). From the
      time of extubation, patients had access to an opioid (fentanyl) via a self
      controlled analgesia device. The number of doses of analgesics needed during the
      hospital stay was significantly higher in the Coblator group (P = 0.020). During
      the 14-day follow-up, no significant differences were found in pain scores,
      return to solid food or subjective working ability between the groups.
      Considering the overall outcome of the patients the results did not favor
      coblation technique over bipolar scissors.

PMID- 18034259
TI  - Comparative characterization of mouse rectum CMT93-I and -II cells by expression
      of claudin isoforms and tight junction morphology and function.
AB  - Recent studies suggest that the morphological and physiological properties of
      tight junctions (TJs) are determined by the combination and mixing ratios of
      claudin isoforms. In this study, we tried to characterize mouse cell lines by
      expression of claudin isoforms to use for studying epithelial TJs by
      overexpression or suppression of claudin(s) in the cells and found that claudin-2
      was expressed in a few mouse rectum carcinoma cells, CMT93 cells. We have
      isolated CMT93-I and -II cells from CMT93 cells by immunohistochemical screening
      for the presence or absence of claudin-2 expression. Immunofluorescence and RT
      PCR analyses showed that expression of claudin-4, -6, -7 and -12 was detected in
      both cell lines, but claudin-2 was only expressed in CMT93-II cells. There were
      no differences in paracellular permeability between CMT93-I and -II cells
      examined by 4 kDa FITC-dextran and fluorescein sodium, or in the number of TJ
      strands examined by freeze-fracture electron microscopy. However, the
      transepithelial electrical resistance (TER) of CMT93-I cells was approximately
      6.5 times higher than that of CMT93-II cells, suggesting that expression of
      claudin-2 may be related to decreased TER. Comparative examinations of CMT93-I
      and -II cells provide a clue how the combination and mixing ratios of claudin
      isoforms regulate the paracellular permeability.

PMID- 18034260
TI  - Muscle sympathetic nerve activity at rest compared to exercise tolerance.
AB  - Cardiovascular autonomic function is associated with physical performance and
      exercise training adaptation. The association between physical performance and
      sympathetic regulation is not well known. We hypothesized that sympathetic
      nervous system activity is associated with physical performance among male
      runners. The study population included 26 healthy male club runners [age 33 +/- 5
      years, body mass index (BMI) 24 +/- 1 kg/m(2), VO(2max) 58 +/- 5 ml kg(-1) min(
      1); mean +/- SD]. Muscle sympathetic nerve activity (MSNA) was assessed from the
      peroneal nerve by the microneurography technique during 5 min of supine rest.
      Physical performance was assessed by time to exhaustion during treadmill running.
      The mean resting MSNA was 20 +/- 6 bursts min(-1) (range 6-34). The mean time to
      exhaustion was 1,005 +/- 136 s (range 720-1260). When the study group was divided
      into tertiles according to their running performance (866 +/- 69, 994 +/- 30 and
      1154 +/- 71 s in time to exhaustion, P < 0.0001 between the groups), MSNA was
      lower (P = 0.032) in the group with the best running performance (16 +/- 5 bursts
      min(-1)) compared to those with the worst running performance (23 +/- 7 bursts
      min(-1)). In conclusion, baseline sympathetic activity, measured by a
      microneurography at rest, may be associated with the maximal running performance
      of healthy subjects.

PMID- 18034261
TI  - Mechanisms of protection against pulmonary hyperbaric O(2) toxicity by
      intermittent air breaks.
AB  - Intermittent exposure to air is used as a protective strategy against hyperbaric
      O(2) (HBO(2)) toxicity. Little is known about optimal intermittent exposure
      schedules and the mechanism of protection. In this study, we examined the role of
      antioxidant enzymes, and inflammatory cytokines in the mechanism of HBO(2)
      tolerance by intermittent air breaks. One group of rats was exposed continuously
      to 282 kPa O(2) until death. Other groups were exposed to 30, 60, and 120 min
      intervals of HBO(2) with different numbers of intermittent 30 min air breaks (1
      12 breaks). After the final break, animals were exposed to HBO(2) until death. In
      a separate experiment, animals were sacrificed before terminal exposure and lung
      tissues were collected for analysis of gene expression. Two intermittent
      schedules with 6 h cumulative O(2) time (30/30 and 60/30 min schedules) were
      compared with continuous exposure to HBO(2) for 6 h and with intermittent
      exposure of 8 h (120/30 min schedule) duration. Continuous exposure resulted in
      activation of inflammatory cytokine TNF-alpha and IL-1beta mRNA expression, an
      increase in lung protein nitration and activation of inducible NOS (iNOS) mRNA.
      Inflammatory response was not observed at intermittent exposures of the same
      cumulative O(2) time duration (30/30 and 60/30 min schedule). Expression of heme
      oxygenase-1 (HO-1) mRNA was significantly increased in all exposure groups while
      manganese superoxide dismutase (MnSOD) mRNA expression was increased only in
      continuous and 120/30 exposure groups. Results show that intermittent exposure to
      air protects against pulmonary HBO(2) toxicity by inhibiting inflammation. The
      mechanism of inhibition may involve the antiinflammatory and antioxidative effect
      of HO-1 but some other mechanisms may also be involved in protection by
      intermittent air breaks.

PMID- 18034262
TI  - New insights on sucrose metabolism: evidence for an active A/N-Inv in
      chloroplasts uncovers a novel component of the intracellular carbon trafficking.
AB  - The presence of sucrose (Suc) in plastids was questioned for several decades.
      Although it was reported some decades ago, neither Suc transporters nor Suc
      metabolizing enzymes were demonstrated to be active in those organelles. By
      biochemical, immunological, molecular and genetic approaches we show that
      alkaline/neutral invertases (A/N-Invs) are also localized in chloroplasts of
      spinach and Arabidopsis. A/N-Inv activity and polypeptide content were shown in
      protein extracts from intact chloroplasts. Moreover, we functionally
      characterized the Arabidopsis At-A/N-InvE gene coding for a chloroplast-targeted
      A/N-Inv. The At-A/N-InvE knockout plants displayed a lower total A/N-Inv activity
      in comparison with wild-type plants. Furthermore, neither A/N-Inv activity nor
      A/N-Inv polypeptides were detected in protein extracts prepared from chloroplasts
      of mutant plants. Also, the measurement of carbohydrate content, in leaves
      harvested either at the end of the day or at the end of the night period,
      revealed that the knockout plants showed a decrease in starch accumulation but no
      alteration in Suc levels. These are the first results demonstrating the presence
      of a functional A/N-Inv inside chloroplasts and its relation with carbon storage
      in Arabidopsis leaves. Taken together our data and recent reports, we conclude
      that the participation of A/N-Invs in the carbon flux between the cytosol and the
      plastids may be a general phenomenon in plants.

PMID- 18034263
TI  - Guidelines for neuropathologic diagnostics of perinatal unexpected loss and
      sudden infant death syndrome (SIDS): a technical protocol.
AB  - In light of the growing information on the pathophysiology and clinical aspects
      of unexpected perinatal loss and sudden infant death syndrome (SIDS), a novel
      approach to the inherent problems by pathologists has become necessary. Herein,
      we propose an up-to-date protocol for accurate examination of the central
      autonomic nervous system and of the cardiac conduction system, which can
      encompass morphological and/or functional abnormalities of reliable epicritical
      value in unexplained perinatal loss and SIDS, particularly in those cases (still
      quite numerous) lacking adequate clinical documentation. Anatomo-pathologic
      examination of the central autonomic nervous system includes an in-depth study on
      histological serial sections of the brainstem, cerebellum, and spinal cord, where
      the main structures participating in control of the vital functions are located.
      For the histological study of the cardiac conductions system, serial sections
      were obtained from two blocks, including the sino-atrial node and the atrio
      ventricular system, respectively. This type of updated investigation is yielding
      important arguments for a broader discussion of the pathogenesis of unexpected
      stillbirth, early neonatal death, and SIDS, besides allowing a more complete
      forensic-medical documentation of individual cases.

PMID- 18034264
TI  - Differential expression of stromal MMP-1, MMP-9 and TIMP-1 in basal cell
      carcinomas of immunosuppressed patients and controls.
AB  - Matrix metalloproteinases (MMPs) have an important role in the initiation,
      growth, and invasion of malignant tumors. Basal cell cancer (BCC) is the most
      common human malignancy. The risk of BCC is 10-16 times higher among organ
      transplant recipients compared with the nontransplanted population. The aim of
      this study was to compare the expression of several MMPs and their tissue
      inhibitors (TIMPs) in BCCs from kidney transplant recipients and controls.
      Expression of MMPs-1, -7, -8, -9, -10, -13, -26, and TIMPs-1 and -3 was evaluated
      by immunohistochemistry in 25 samples of BCC of kidney transplant recipients and
      25 matched controls representing superficial and nodular subtypes. No significant
      differences were detected in MMP expression of BCC tumor cells between
      immunocompetent and immunodeficient patients. However, MMPs-1 and -9 and TIMP-1
      were expressed more frequently in stromal macrophages in the BCCs of
      immunocompetent patients. When tumor subtypes were compared irrespective of the
      patient group, more MMP-1-positive fibroblasts and MMP-9-positive neutrophils
      were detected in the superficial subtype, while stromal MMP-10 expression was
      more abundant in nodular tumors. Our results suggest that abundant peritumoral
      expression of TIMP-1 in non-immunocompromised patients limits ECM degradation
      permissive for cancer cell migration.

PMID- 18034265
TI  - Inducible nitric oxide synthase inhibition influenced granuloma formation with
      suppressed collagen expression in myositis caused by Toxocara canis in mice.
AB  - The role of nitric oxide (NO) in granuloma pathology is largely unclear to date.
      We investigated the role of NO in fibrotic granuloma development in the
      musculature of mice infected with Toxocara canis from 1 day (dpi) to 8 weeks post
      infection (wpi) using the NO synthase (NOS) inhibitors, L-NIL (l-N6-1-iminoethyl
      lysine). In infected mice, elevated serum NO concentrations were seen at 1 dpi
      (204.1 +/- 0.2 microM) and 1 wpi (145.1 +/- 0.2 microM); it declined drastically
      from 4 wpi onwards (57.0 +/- 0.1 microM). In L-NIL-treated mice, the NO
      concentration was drastically reduced from 15% during 1 wpi; thereafter, it was
      restored to almost half that in infected mice. Inducible NOS expression was
      enhanced in infected and L-NIL-treated mice at 4 wpi but declined at 8 wpi as
      assessed by immunohistochemistry. L-NIL treatment resulted in large, irregularly
      shaped granulomas with suppressed collagen contents at 4 wpi but not at 8 wpi.
      The suppressed collagen contents might have been related to decreased serum NO
      and Th2-type cytokine of interleukin-4 but not Th1-type cytokine of interferon
      gamma expression.

PMID- 18034266
TI  - In vivo analysis of Drosophila SU(Z)12 function.
AB  - Polycomb group (PcG) proteins are required to maintain a stable repression of the
      homeotic genes during Drosophila development. Mutants in the PcG gene Supressor
      of zeste 12 (Su(z)12) exhibit strong homeotic transformations caused by
      widespread misexpression of several homeotic genes in embryos and larvae. Su(z)12
      has also been suggested to be involved in position effect variegation and in
      regulation of the white gene expression in combination with zeste. To elucidate
      whether SU(Z)12 has any such direct functions we investigated the binding pattern
      to polytene chromosomes and compared the localization to other proteins. We found
      that SU(Z)12 binds to about 90 specific eukaryotic sites, however, not the white
      locus. We also find staining at the chromocenter and the nucleolus. The binding
      along chromosome arms is mostly in interbands and these sites correlate precisely
      with those of Enhancer-of-zeste and other components of the PRC2 silencing
      complex. This implies that SU(Z)12 mainly exists in complex with PRC2.
      Comparisons with other PcG protein-binding patterns reveal extensive overlap.
      However, SU(Z)12 binding sites and histone 3 trimethylated lysine 27 residues
      (3meK27 H3) do not correlate that well. Still, we show that Su(z)12 is essential
      for tri-methylation of the lysine 27 residue of histone H3 in vivo, and that
      overexpression of SU(Z)12 in somatic clones results in higher levels of histone
      methylation, indicating that SU(Z)12 is rate limiting for the enzymatic activity
      of PRC2. In addition, we analyzed the binding pattern of Heterochromatin Protein
      1 (HP1) and found that SU(Z)12 and HP1 do not co-localize.

PMID- 18034267
TI  - From bench to bed: the potential of stem cells for the treatment of Parkinson's
      disease.
AB  - Parkinson's disease (PD) is the most common movement disorder. The neuropathology
      is characterized by the loss of dopamine neurons in the substantia nigra pars
      compacta. Transplants of fetal/embryonic midbrain tissue have exhibited some
      beneficial clinical effects in open-label trials. Neural grafting has, however,
      not become a standard treatment for several reasons. First, the supply of donor
      cells is limited, and therefore, surgery is accompanied by difficult logistics.
      Second, the extent of beneficial effects has varied in a partly unpredictable
      manner. Third, some patients have exhibited graft-related side effects in the
      form of involuntary movements. Fourth, in two major double-blind placebo
      controlled trials, there was no effect of the transplants on the primary
      endpoints. Nevertheless, neural transplantation continues to receive a great deal
      of interest, and now, attention is shifting to the idea of using stem cells as
      starting donor material. In the context of stem cell therapy for PD, stem cells
      can be divided into three categories: neural stem cells, embryonic stem cells,
      and other tissue-specific types of stem cells, e.g., bone marrow stem cells. Each
      type of stem cell is associated with advantages and disadvantages. In this
      article, we review recent advances of stem cell research of direct relevance to
      clinical application in PD and highlight the pros and cons of the different
      sources of cells. We draw special attention to some key problems that face the
      translation of stem cell technology into the clinical arena.

PMID- 18034268
TI  - Placement of C2 laminar screws using three-dimensional fluoroscopy-based image
      guidance.
AB  - The use of C2 laminar screws in posterior cervical fusion is a relatively new
      technique that provides rigid fixation of the axis with minimal risk to the
      vertebral artery. The techniques of C2 laminar screw placement described in the
      literature rely solely on anatomical landmarks to guide screw insertion. The
      authors report on their experience with placement of C2 laminar screws using
      three-dimensional (3D) fluoroscopy-based image-guidance in eight patients
      undergoing posterior cervical fusion. Overall, fifteen C2 laminar screws were
      placed. There were no complications in any of the patients. Average follow-up was
      10 months (range 3-14 months). Postoperative computed tomographic (CT) scanning
      was available for seven patients allowing evaluation of placement of thirteen C2
      laminar screws, all of which were in good position with no spinal canal
      violation. The intraoperative planning function of the image-guided system
      allowed for 4-mm diameter screws to be placed in all cases. Using modified Odom's
      criteria, excellent or good relief of preoperative symptoms was noted in all
      patients at final follow-up.

PMID- 18034269
TI  - A link between copper and dental caries in human teeth identified by X-ray
      fluorescence elemental mapping.
AB  - Quantitative X-ray fluorescence imaging of sections of human teeth revealed an
      increased concentration of copper and zinc in carious regions of dentine compared
      with unaffected portions of the tooth. Higher-resolution images provided strong
      evidence that the copper was transported and localized mainly in the dentinal
      tubules. While similar levels of zinc were found in these areas and concentrated
      in the tubules, zinc was also more evident in the hydroxyapatite, and the
      increase in zinc levels compared with the levels in background (normal) areas was
      less than that for copper. These results suggest a role for copper and zinc in
      the formation and progression of dental caries and present a potential point of
      intervention for treatment.

PMID- 18034270
TI  - Tuberculous meningoencephalitis in a pregnant woman presenting 7 years after
      removal of a cerebral granuloma.
AB  - We describe the unusual case of a young woman with a history of seizures and a
      granulomatous, likely tuberculous brain lesion that was surgically removed. She
      had an uneventful recovery without any additional therapy other than anti
      epileptics. Seven years later, she presented during pregnancy with culture
      confirmed tuberculous meningoencephalitis. This case highlights the spectrum of
      tuberculous central nervous system disease and the challenges in diagnosis.

PMID- 18034271
TI  - Non-vascular vision loss in pseudoxanthoma elasticum.
AB  - Pseudoxanthoma elasticum patients with angioid streaks are well-known to have
      acute vision loss due to choroidal bleeding. However, chronic vision loss due to
      macular atrophy is less well characterized. We describe a patient with sub-acute
      vision loss in one eye due to loss of macular retinal pigment epithelium
      function. Autofluorescence and pattern electroretinogram were useful adjuncts to
      help diagnose the source of her vision loss.

PMID- 18034272
TI  - Pattern-reversal electroretinograms and visual evoked potentials in retinitis
      pigmentosa.
AB  - OBJECTIVE: To analyze pattern electroretinograms (PERGs) and pattern visual
      evoked potentials (PVEPs) in retinitis pigmentosa (RP) patients. METHODS: PERGs
      and PVEPs were recorded in 106 eyes of 53 RP patients. A RETIport system was used
      for stimulation and recording. RESULTS: Reproducible PERGs were found in 17 (32%)
      of the patients, from only one eye in 4 of the 17 patients. We failed to record a
      normal PERG in any patient. All 53 patients gave reproducible PVEPs. The patients
      could be divided into three groups according to the waveform of the response. In
      the first group (n = 17), all patients produced PVEPs with a characteristic,
      triphasic shape, but with smaller amplitudes. In the second group (n = 16), the
      PVEPs displayed doubled P100 peaks, with components separated by about 50 ms. The
      recordings in the third group (n = 20) were broad in shape and characterized by a
      greatly increased N70-N170 latency difference and decreased amplitudes.
      CONCLUSIONS: In the population of RP patients, different types of PVEP waveform
      alterations can be observed. The appearance of both the responses with decreased
      amplitude and those with broad, doubled P100 waves might reflect differences in
      central retinal degeneration. The significance and pathological background of
      these PVEP alterations need further investigations.

PMID- 18034273
TI  - Structural and functional maturation of the retina of the albino Hartley guinea
      pig.
AB  - PURPOSE: Altricial animals, such as rats and mice, are born with their eyes
      closed, compared to precocial animals, such as guinea pigs and humans, which have
      their eyes opened at birth. The purpose of this study was to investigate if the
      retina of guinea pigs (precocial animal) is subjected to a postnatal maturation
      process similar to that previously reported for rodents. METHODS: Photopic and
      scotopic electroretinograms (ERG) and retinal histology were obtained from albino
      guinea pigs aged P1 to P75. RESULTS: Photopic ERG responses reached maximal
      amplitudes at P5 (a-and b-waves), that is 5 days (b-wave) to 10 days (a-wave)
      earlier than scotopic responses. However, the postnatal gain in b-wave amplitude
      was significantly (P < 0.05) more important for the cone (73.38 +/- 4.4%) signal
      than for the rod (15.23 +/- 3.96%), suggesting that the rod function is more
      mature at birth. Similarly, the short latency photopic oscillatory potential (ie:
      OP2) reached its maximal value 5 days (P10) earlier than its scotopic equivalent
      (P15), while the long latency OPs (ie: OP3, OP4), reached their maximal values
      nearly 20 days sooner in scotopic condition. Finally retinal histology revealed a
      thinning of the retina with age, the latter being most pronounced at the level of
      the ganglion cell layer (GCL). CONCLUSION: Our results thus confirm that despite
      its relative maturity at birth (compared to rodents), the retina of newborn
      albino guinea pigs undergoes significant postnatal maturation modifying its
      structure as well as its function, albeit not as extensive as that previously
      documented for altricial animals.

PMID- 18034274
TI  - Transforming growth factor-beta receptor antagonism attenuates myocardial
      fibrosis in mice with cardiac-restricted overexpression of tumor necrosis factor.
AB  - The mechanisms that are responsible for the development of myocardial fibrosis in
      inflammatory cardiomyopathy are unknown. We have previously generated lines of
      transgenic mice with cardiac-restricted overexpression of tumor necrosis factor
      (MHCsTNF mice), a pro-inflammatory cytokine. The MHCsTNF mice develop a heart
      failure phenotype that is characterized by progressive myocardial fibrosis, as
      well as increased levels transforming growth factor-beta (TGF-beta)(mRNA and
      protein. In order to determine whether TGF-beta-mediated signaling was
      responsible for the myocardial fibrosis observed in the MHCsTNF mice, we treated
      MHCsTNF and littermate control mice from 4 to 12 weeks of age with a novel orally
      available TGF-beta receptor antagonist (NP-40208). At the time of terminal study,
      myocardial collagen content was determined using the picrosirius red technique,
      and left ventricular (LV) systolic and diastolic function were determined using
      the Langendorff method. Treatment with NP-40208 resulted in a significant (P <
      0.05) 65% decrease in nuclear translocation of Smad 2/3, a significant (P <
      0.05), decrease in the heart-weight to body-weight ratio from 6.5 to 5.7, a
      approximately 37% decrease in fibrillar collagen content (P < 0.01) and a
      significant (P < 0.05) decrease in the LV chamber stiffness by approximately 25%
      in the MHCsTNF mice when compared to diluent-treated controls. Treatment with NP
      40208 had no discernable effect on LV systolic function, nor any effect on
      cardiac myocyte size or fetal gene expression in the MHCsTNF mice. Taken
      together, these observations suggest that sustained pro-inflammatory signaling in
      the adult heart is associated with a pro-fibrotic phenotype that arises, at least
      in part, from TGF-beta-mediated signaling, with resultant activation of Smad 2/3,
      leading to increased myocardial fibrosis and increased LV diastolic chamber
      stiffness.

PMID- 18034275
TI  - Increased myocardial contractility and enhanced exercise function in transgenic
      mice overexpressing either adenylyl cyclase 5 or 8.
AB  - OBJECTIVE: ss-adrenergic receptors (ssARs) are powerful regulators of cardiac
      function in vivo, activating heterotrimeric G proteins and the effector molecule
      adenylyl cyclase (AC). Interestingly, cardiac-specific overexpression of
      different AC isoforms leads to variable changes in cardiac function. Whether AC
      overexpression affects intrinsic cardiac contractility in an isoform-specific
      fashion determining a change in exercise capacity is currently unknown. METHODS:
      To address this issue, we performed load-independent measurements of cardiac
      systolic and diastolic function by pressure-volume (PV) loop analysis in intact
      wild-type mice (WT) and transgenic mice overexpressing the AC isoforms 5 or 8.
      RESULTS: Here we show that cardiac overexpression of either AC5 or AC8 transgenic
      mice determined an increase in intrinsic cardiac contractility. Interestingly,
      AC8 transgenic mice displayed a significantly greater increase in cardiac
      contractility and improved active phase of relaxation. Despite these differences
      detected by PV loop analysis, both AC5 and AC8 mice showed a marked increase in
      exercise capacity on treadmill testing. CONCLUSIONS: Our results demonstrate that
      load-independent measurements of cardiac function are needed to compare different
      groups of genetically-modified mouse models and to detect subtle AC isoform
      specific changes in cardiac performance.

PMID- 18034276
TI  - Should all patients undergo postoperative duplex imaging to detect a deep vein
      thrombosis after varicose vein surgery?
AB  - OBJECTIVES: Deep vein thrombosis (DVT) is a serious complication of varicose vein
      surgery, with attendant risks of pulmonary embolization. Prospective duplex
      screening identifies DVT in 5% of patients compared to clinical incidence of
      approximately 1%. Universal duplex screening is costly, and the benefits of
      diagnosing subclinical DVT are unproven. This study evaluates whether a policy of
      using clinical indications (leg swelling) to determine the need for duplex
      imaging is safe after varicose vein surgery. METHODS: Patients undergoing
      varicose vein surgery over a 4-year period were studied. Postoperative venous
      duplex imaging was performed if leg swelling occurred within 6 weeks of surgery.
      Long-term follow-up was performed to detect any missed occurrence of clinical DVT
      or pulmonary embolism. RESULTS: A total of 411 patients had 491 leg operations
      with 80 bilateral procedures (27%); 29 patients with leg swelling underwent
      duplex imaging, 5 of whom had duplex-proven DVT. No patient without early
      clinical signs went on to develop clinical DVT on long-term follow-up.
      CONCLUSION: A policy of using clinical signs as a triage for duplex imaging
      detected all clinically significant DVTs and generated manageable workloads for
      our vascular laboratory.

PMID- 18034277
TI  - Quality improvement guidelines for endovascular treatment of iliac artery
      occlusive disease.
AB  - Endovascular therapy is the treatment of choice for type A and the preferred
      treatment for type B lesions. In selective patients, this type of treatment can
      be applied in type C and even type D lesions. Ipsilateral femoral, contralateral
      femoral, and brachial approach and both the intraluminal and subintimal space can
      be used for successful recanalization. The application of stents has improved the
      immediate hemodynamic and probably long-term clinical results of iliac
      percutaneous transluminal angioplasty. However, the superiority of primary or
      direct stenting over selective stenting has not been proven yet. The choice of
      stent type depends on lesion morphology and location but otherwise there is
      insufficient evidence to support the use of a particular stent design. There is
      insufficient evidence to justify routine use of covered stents. All patients
      should receive antiaggregant therapy following endovascular recanalization of
      iliac arteries. There is no consensus regarding prophylaxis with antibiotics in
      iliac recanalization procedures.

PMID- 18034280
TI  - A novel surgical approach to slow-transit constipation: report of two cases.
AB  - INTRODUCTION: Slow-transit constipation after proper diagnosis and extensive
      medical therapy may have a surgical solution. Total abdominal colectomy and
      ileorectal anastomosis, at our institution, is the surgical procedure of choice.
      Nonetheless, patients may reject this alternative because of morbidity.
      DISCUSSION: We report two cases of slow-transit constipation diagnosed after a
      thorough investigation with two colonic transit tests showing slow-transit
      constipation, a normal anorectal manometry, balloon expulsion test, small-bowel
      follow-through, defecography, laboratory and psychologic tests. The patients
      rejected standard surgical treatment (total colectomy + ileorectal anastomosis).
      A colonic bypass with an ileorectal anastomosis, leaving the colon in situ, was
      offered and accepted by the two patients. This was performed laparoscopically
      liberating the cecum and terminal ileum, transecting the terminal ileum through a
      small suprapubic incision, and anastomosing the terminal ileum to the
      rectosigmoid junction intracorporeally. The total surgical time was 50 and 60
      minutes, respectively. Both patients made uneventful recoveries and were
      discharged on the fourth postoperative day. They have completed four and two
      months of close follow-up and at present have one to four bowel movements per day
      with mild abdominal distension and pain. To our knowledge this is the first
      report of colonic bypass for the treatment of slow-transit constipation.

PMID- 18034278
TI  - In vitro mechanisms of lovastatin on lung cancer cell lines as a potential
      chemopreventive agent.
AB  - Lung cancer causes over one million deaths per year worldwide and cigarette
      smoking, the proximate cause, results in a field cancerization of the respiratory
      track. Lung cancer cells or premalignant cells may be susceptible to apoptosis or
      necrosis-inducing agents. Statins inhibit the acetyl coenzyme A pathway reducing
      L-mevalonate that is a precursor to isoprenoids necessary for post-translational
      processing, resulting in apoptosis. Lovastatin was added to four lung cancer cell
      lines and normal human bronchial epithelial cells followed by Western blots to
      evaluate proteins in the cell cycle, oxidant, and apoptotic pathways. Flow
      cytometry revealed significant increases in three of four lung cancer cell lines
      in apoptosis and necrosis after lovastatin treatment at 10 microM for 72 h.
      Lovastatin adversely affected lung cancer cell survival with increases in cell
      cycle check-point inhibitors p21WAF and/or p27KIP and a decrease in cyclin D1.
      All four lung cancer cell lines had a decrease in glutathione after lovastatin
      treatment consistent with reduced protection against reactive oxidant species.
      Three of four lung cancer cell lines had increased cytochrome c release with
      reduced pro-caspase-3 and increases in activated caspase-3. Lovastatin induces
      apoptosis and necrosis in lung cancer cell lines by causing alterations in the
      cell cycle, reducing glutathione, and activating p53, Bax protein, and caspases
      while increasing cytochrome c in apoptosis pathways. Targeting HMG-CoA reductase
      may represent an approach to lung cancer chemotherapy, e.g., reversing ground
      glass opacities detected on CT scans or resolving airway preneoplasias detected
      by bronchoscopy before they progress to malignant transformation.

PMID- 18034282
TI  - Antifungal activity of a new phenolic compound from capitulum of a head rot
      resistant sunflower genotype.
AB  - In a previous study, we observed that bract and corolla extracts from a
      Sclerotinia sclerotiorum-resistant sunflower contained high amounts of the known
      coumarins scopoletin, scopolin, and ayapin. There was a correlation between
      coumarin concentration and disease resistance. Thin layer chromatography showed
      higher concentrations of three other compounds in the resistant genotype when
      compared to the susceptible. A bioassay-directed purification that used column
      chromatography and HPLC allowed the isolation of a new compound, 3-acetyl-4
      acetoxyacetophenone, and known compounds, demethoxyencecalin and 3-acetyl-4
      hydroxyacetophenone. Structures were assigned from spectral data, and
      bioactivities were characterized by in vitro bioassays against S. sclerotiorum.
      The new compound, 3-acetyl-4-acetoxyacetophenone, had an antifungal activity
      similar to the coumarin ayapin, previously described as a potent Sclerotinia
      inhibitor. The speed and simplicity by which these compounds can be detected make
      them suitable for use in screening procedures that may identify genotypes with
      valuable levels of resistance. A screening of seven sunflower genotypes in a
      field experiment showed a correlation between these compounds and resistance to
      Sclerotinia.

PMID- 18034283
TI  - Neoplastic transformation and induction of H+,K+ -adenosine triphosphatase by N
      methyl-N'-nitro-N-nitrosoguanidine in the gastric epithelial RGM-1 cell line.
AB  - N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces gastric cancer in animal
      models. We established an MNNG-induced mutant of the rat murine RGM-1 gastric
      epithelial cell line, which we named RGK-1, that could be used as an in vitro
      model of gastric cancer. This cell line showed signs of neoplasia and
      transformation, in that it lost contact inhibition and formed tumors in nude
      mice. The mutant cells also expressed parietal cell-specific H(+),K(+)-adenosine
      triphosphatase (H(+),K(+)-ATPase), which parent RGM-1 did not. The results
      suggested that parent RGM-1 cells were gastric progenitor cells. This mutant RGK
      1 cell line will contribute to future investigation on gastric carcinogenesis and
      to the development of other pathophysiologic fields.

PMID- 18034284
TI  - Shear bond strength of self-etching adhesive systems to Er:YAG-laser-prepared
      dentin.
AB  - This study was conducted to compare the shear bond strengths of composite resin
      bonded to Er:YAG laser or bur-prepared dentin surfaces using three self-etching
      adhesive systems. The occlusal surfaces of 120 human third molars were ground
      flat to expose dentin. The dentin was prepared using either a carbide bur or an
      Er:YAG laser at 350 mJ/pulse and 10 Hz (fluence, 44.5 J/cm(2)). Three different
      self-etching adhesive systems were applied: iBond, Xeno III and Clearfil SE Bond.
      Rods of composite resin were bonded to dentin surfaces and shear bond tests were
      carried out. Both dentin surfaces after debonding and resin rods were observed
      using a scanning electron microscope. When the Xeno III was used, no difference
      was observed on shear bond strength values when bur and Er:YAG laser were
      compared. When using iBond and Clearfil SE Bond, bond strength values measured on
      Er:YAG-laser-prepared surfaces were lower than those observed on bur-prepared
      surfaces. The absence of smear layer formation during the preparation of the
      dentin by the Er:YAG laser did not improve the adhesion values of self-etching
      adhesive systems.

PMID- 18034285
TI  - Time-resolved measurement shows a spectral distribution shift in an intense
      pulsed light system.
AB  - For an intense pulsed light (IPL) device, knowledge of the spectral output is
      useful in order to provide effective treatment and target specific structures in
      the skin. It is also a requirement in order to perform a safety assessment. A
      novel spectral measurement system has been developed to detect the optical
      radiation output of intense pulsed light devices. The system has a time
      resolution of 450 mus and a wavelength resolution of 0.6 nm. This enabled us to
      observe spectral changes, both within a pulse and between pulses, in a pulse
      train. The output from a free discharge IPL source and four different treatment
      handpieces was measured. A shift in the spectral distribution between pulses, and
      within a pulse, was discovered. The spectral shift is more prominent for higher
      radiant exposures.

PMID- 18034286
TI  - Skeletal anchorage in orthodontics--basics and clinical application.
AB  - This review article describes the basics and clinical applications of skeletal
      anchorage in orthodontics, namely: areas of indication, anchorage devices,
      insertion areas, indications, potential complications, and their use in growing
      patients. The areas for skeletal anchorage include orthodontic-prosthetic
      anchorage, orthodontic anchorage, and skeletal anchorage in orthopedic therapy
      procedures. The anchorage devices currently available are: prosthetic implants,
      mini screws, palatal implants, onplants, bone anchors, zygoma wires and
      skeletally-supported distractors. The insertion areas described so far (according
      to therapeutic procedure and bone supply available) include edentulous jaw
      sections, the interdental septum, infra-apical and supra-apical areas, the palate
      (median, paramedian, lateral), the retromolar area, and the zygomatic bone. Force
      systems are applied (direct or indirect anchorage) according to surgical and
      orthodontic or orthopedic requirements. Skeletal anchorage devices should be
      selected according to the following criteria. Is the anchorage task unifunctional
      or multifunctional? How many anchorage devices are required for the therapy in
      question? What is the success rate of the various anchorage devices; what are the
      applicable biomechanics and soft tissue or hard tissue conditions in the
      insertion area? The success rates for miniscrews are currently between 80% and
      90%, and over 90% for palatal implants. The potential of skeletal anchorage is
      broadening the current orthodontic treatment spectrum, guaranteeing the
      practitioner absolute control of anchorage by avoiding the unpredictable
      reactions of periodontal anchorage, leading to a reduction in unwanted side
      effects.

PMID- 18034287
TI  - Interrelation between occlusal findings and orofacial myofunctional status in
      primary and mixed dentition: Part III: Interrelation between malocclusions and
      orofacial dysfunctions.
AB  - AIM: It was the purpose of this study to analyze the relationship between
      selected types of malocclusion and specific types of static and dynamic orofacial
      dysfunction and to compare the results with subjects presenting regular
      occlusion. We aimed to identify which orthodontic and functional symptoms in
      early dentition would lead to malocclusion later on. SUBJECTS AND METHODS:
      Occlusal relations and myofunctional status were evaluated in 3,041 children. We
      diagnosed dynamic and static myofunctional disorders as well as oral habits by
      means of functional examinations. RESULTS: No orofacial dysfunctions were found
      in 11.2% of the children with primary dentition and in 10.2% of the children with
      early mixed dentition. We observed no correlation between the existence of
      distoclusion and functional disorders. Lateral crossbite in mixed dentition, as
      well as increased overjet and frontal open bite in primary and early mixed
      dentitions appeared significantly more frequently in children with orofacial
      dysfunctions. Individuals with frontal open bite, lateral crossbite, reduced and
      increased overjet presented static dysfunctions significantly more frequently
      than those in dentitions with normal occlusion. Dynamic dysfunctions were
      significantly more prevalent in subjects with frontal open bite and lateral
      crossbite than in those with normal occlusion. CONCLUSIONS: Our results enable us
      to prognosticate which children risk future orthodontic problems. Any child
      presenting one of the four occlusal disorders plus one static or two dynamic
      dysfunctions is a child more likely to develop orthodontic problems later on.
      Orthodontic prevention and early treatment must include functional rehabilitation
      so as to eliminate or at least diminish those factors causing undesirable
      developments.

PMID- 18034288
TI  - Reliability of a Method for Computing Facial Symmetry Plane and Degree of
      Asymmetry Based on 3D-data.
AB  - OBJECTIVE: The objective of this study was to analyze the reliability of a
      landmark-independent method for determining the facial symmetry plane and degree
      of asymmetry based on three-dimensional data from the facial surface from two
      sets of recordings, one performed consecutively and one performed on different
      days. MATERIALS AND METHODS: We used an optical 3D-sensor to obtain the facial
      data of one male subject in two sets of ten measurements: the first taken
      consecutively and the second on different days. The symmetry plane and degree of
      asymmetry were calculated for each of the resulting twenty sets of data. One set
      of data was analyzed ten times for control purposes. The calculation of the mean
      deviation angle between the symmetry planes served as a measure of the
      reproducibility of these results. RESULTS: Although the mean angular deviations
      of the computed symmetry planes, 0.134 degrees (for ten consecutively captured
      images) and 0.177 degrees (for the ten images captured on different days), were
      each significantly higher than the mean angular deviation (0.028 degrees)
      calculated from ten analyses of a single image, they can still be regarded as
      very small. There were no significant differences in the degree of asymmetry
      among the three measurement sets. The standard deviations revealed low values.
      CONCLUSIONS: This method can be used to compute with high reliability the
      symmetry planes and degree of asymmetry of facial 3D-data. The color-coded
      visualization of asymmetrical facial regions makes it possible for this
      analytical procedure to capture the asymmetries of facial soft tissue with
      substantially greater precision than 2-dimensional en face images.

PMID- 18034289
TI  - Molar inclination in panoramic x-rays as an indicator for extraction decisions.
AB  - OBJECTIVE: Recommendations concerning the necessity of extraction therapy are
      often based upon clinical findings and panoramic x-rays. Since the success of
      this approach greatly depends on the individual examiner's clinical expertise, we
      believed it to be of interest to evaluate whether panoramic x-ray findings alone
      suffice for making the decision to extract. The aim of this study was to evaluate
      whether the need for extraction therapy can be verified by measuring the
      angulations between the first and second lower molars. MATERIAL AND METHODS:
      Orthopantomograms of 30 patients who underwent extraction of four premolars were
      examined prior to and after treatment. Initial study casts were also evaluated
      for any correlations between molar inclination and other examination parameters.
      Orthopantomograms of 30 patients who had experienced comprehensive orthodontic
      treatment without extraction served as age- and gender-matched controls. RESULTS:
      Contrary to expectation, the lower second molars showed a stronger mesial
      inclination before rather than after treatment, and the changes were highly
      significant. The controls also showed highly significant changes on the left
      side. The extraction and non-extraction groups did not differ significantly in
      terms of molar inclination at the beginning of treatment. Gender differences
      occurred in both groups, but only on one side. No other findings indicated gender
      differences in terms of molar inclination. CONCLUSION: Our data failed to prove a
      correlation between distally- inclined lower second molars in the panoramic x-ray
      and the indication of extraction therapy.

PMID- 18034290
TI  - Longitudinal changes in temporomandibular disorders in young adults: indication
      for systematic temporomandibular joint screening.
AB  - OBJECTIVE: The aim of this study was to investigate longitudinal changes in
      temporomandibular joint function in young adults in terms of clinical and
      subclinical temporomandibular disorders (TMD), and to identify patients at risk
      for clinically manifest TMD. SUBJECTS AND METHODS: Ninety-one consecutive dental
      students were surveyed over a mean period of 2.4 years. The temporomandibular
      joint and masticatory muscles were analyzed by means of the Manual Functional
      Analysis. Examinations took place during the first (T1) and sixth (T2) terms of
      dental training. RESULTS: The prevalence of subclinical TMD decreased from 16.5%
      to 15.4%, while that of clinical TMD rose from 19.8% (T1) to 24.2% (T2). Subjects
      with subclinical TMD at T1 showed the most pronounced fluctuation, and were about
      equally likely to improve, remain stable or deteriorate. The incidence of
      clinical TMD in the subclinical TMD-group was 28.6%, that is, almost every third
      subject developed clinical TMD over a 2.4-year period. CONCLUSIONS: Should
      clinical TMD become apparent during orthodontic treatment, the patient might
      attribute it to the therapy, rather than to the subclinical disorder at baseline.
      It thus makes therapeutic and forensic sense to carry out systematic TMJ
      screening in all adult patients prior to orthodontic treatment, in order to
      identify patients at risk.

PMID- 18034291
TI  - Dentoalveolar open bite treatment with spur appliances.
AB  - OBJECTIVE: The purpose of this prospective, longitudinally-controlled study was
      to analyze the isolated effect of spurs on the craniofacial and dentoalveolar
      complex of patients presenting anterior open bite due to tongue dysfunction.
      MATERIAL AND METHODS: Following a standardized treatment protocol, fifteen
      patients (mean age 13 years, 10 months+/-5 years, 7 months) underwent treatment
      with a fixed palatal spur appliance for a mean duration of 9.13 months. The
      cephalometric analysis was based on lateral cephalograms taken before (T1) and
      directly after the spur therapy (T2). RESULTS: All patients experienced an
      elongation of the maxillary and mandibular alveolar processes. The alveolar
      process height of the maxilla showed a highly significant mean growth increment
      of 1.61 mm, the alveolar process height of the mandible of 1.36 mm. The mean
      increase in overbite was 1.95 mm and highly significant. In addition, after spur
      therapy, a significant uprighting of the lower incisors was observed, which also
      resulted in a significant increase in the overjet. CONCLUSIONS: With the help of
      spurs, an elongation of the alveolar process heights of the upper and lower jaws
      was achievable for all patients presenting an anterior open bite due to tongue
      dysfunction. The results indicate a change in the neuromuscular behavior pattern
      of the tongue which brought about the correction of the dysfunction and, finally,
      the increase in overbite.

PMID- 18034292
TI  - Glucose loading precipitates focal lactic acidosis in the vulnerable medial
      thalamus of thiamine-deficient rats.
AB  - Glucose loading in thiamine-deficient patients is known to precipitate Wernicke's
      Encephalopathy; however, the mechanisms responsible have not been fully
      elucidated. Lactate accumulation occurs in brains of thiamine-deficient rats. In
      order to determine whether glucose loading in thiamine-deficient rats causes
      selective lactic acidosis in vulnerable brain structures, cerebral pH was
      measured autoradiographically using 14-labeled 5,5-dimethyloxazolidine-2, 4-dione
      ([(14)C]DMO) in the medial thalamus, a vulnerable brain region, versus cerebral
      cortex, a brain region that is spared in thiamine deficiency. Following
      administration of a glucose load, regional lactate levels and de novo lactate
      synthesis measured by (1)H-(13)C-NMR spectroscopy, increased significantly to
      21.86 +/- 3.04 mumol/g (wet weight) in the medial thalamus (p < 0.001) and pH in
      this brain region was decreased significantly from 7.08 +/- 0.04 to 6.87 +/- 0.05
      (p < 0.001). No such changes were observed in cerebral cortex following a glucose
      load. These results demonstrate that the increased production and accumulation of
      brain lactate result in acidosis following glucose loading in thiamine
      deficiency. Alterations of brain pH could contribute to the pathogenesis of
      thalamic neuronal damage and consequent cerebral dysfunction in Wernicke's
      Encephalopathy.

PMID- 18034293
TI  - Sulfite increases lipoperoxidation and decreases the activity of catalase in
      brain of rats.
AB  - The main objective of this study was to investigate the in vitro effects of
      sulfite, a metabolite accumulated in isolated sulfite oxidase deficiency, on Na
      (+), K (+)-ATPase activity and on some parameters of oxidative stress, namely
      thiobarbituric acid-reactive substances (TBARS) and catalase activity
      (antioxidant enzyme) in cerebral cortex, striatum and hippocampus from 10- and 60
      day-old rats. Results showed that 500 microM sulfite significantly increased
      TBARS and reduced catalase activity in the cerebral structures studied from
      neonates and adults rats; in contrast, sulfite did not alter Na(+), K(+)-ATPase
      activity. Our present findings show that sulfite increases lipid peroxidation and
      decreases antioxidant enzyme defenses in rat brain, suggesting an induction of
      oxidative stress. We presumed that oxidative stress might be, at least in part,
      associated with the neuronal dysfunction of patients affected by isolated sulfite
      oxidase deficiency.

PMID- 18034294
TI  - Comparison of form and motion coherence processing in autistic spectrum disorders
      and dyslexia.
AB  - A large body of research has reported visual perception deficits in both people
      with dyslexia and autistic spectrum disorders. In this study, we compared form
      and motion coherence detection between a group of adults with high-functioning
      autism, a group with Asperger's disorder, a group with dyslexia, and a matched
      control group. It was found that motion detection was intact in dyslexia and
      Asperger. Individuals with high-functioning autism showed a general impaired
      ability to detect coherent form and motion. Participants with Asperger's syndrome
      showed lower form coherence thresholds than the dyslexic and normally developing
      adults. The results are discussed with respect to the involvement of the dorsal
      and ventral pathways in developmental disorders.

PMID- 18034295
TI  - Brief report: an autistic spectrum subtype revealed through familial
      psychopathology coupled with cognition in ASD.
AB  - This study identified a possible autistic spectrum subtype expressed through
      family psychopathology coupled with autistic probands' cognitive functioning
      (i.e., an endophenotypic profile). Participants included 24 children with Autism
      Spectrum Disorder (ASD) and 49 children with Learning Disorder (LD). There were
      significantly higher rates of Mood and Anxiety Disorder in first degree maternal
      relatives and of LD and Attention-Deficit Hyperactivity Disorder in first degree
      paternal relatives of ASD probands. Significantly higher visuospatial functioning
      was noted in all ASD probands for which there were higher rates of Mood Disorder
      on the maternal side suggesting a possible marker for an ASD subtype and
      indicating that maternal psychopathology may have a neuroprotective effect on
      visuospatial functioning.

PMID- 18034297
TI  - The relation between social embeddedness and loneliness among older lesbian, gay,
      and bisexual adults in the Netherlands.
AB  - Research has shown that aging lesbians, gay men, and bisexuals (LGBs) often
      experience feelings of loneliness. The main aim of this study was to examine
      whether older LGB adults in the Netherlands are lonelier than their heterosexual
      counterparts and, if so, whether the higher levels of loneliness can be
      attributed to a lower degree of social embeddedness. Using data from the Gay
      Autumn project and the NESTOR survey on Living Arrangements and Social Networks
      of Older Adults, we found that LGB elders were significantly lonelier and less
      socially embedded than heterosexual elders. Compared with their heterosexual
      peers, older LGBs were more likely to have experienced divorce, to be childless
      or to have less intensive contact with their children. They also had less
      intensive contact with other members of their families and they were less
      frequent churchgoers. Their weaker level of social embeddedness, however, only
      partially explained the stronger feelings of loneliness among older LGB adults.
      Nor could their higher levels of loneliness be attributed to other, non-social
      embeddedness factors (health, living conditions, self-esteem, and socioeconomic
      status). Emphasis on other aspects of social embeddedness, such as the quality of
      social relationships in the private domain and minority stress, is an important
      challenge for future research.

PMID- 18034298
TI  - Moderating effects of age on the alcohol and sexual risk taking association: an
      online daily diary study of men who have sex with men.
AB  - Men who have sex with men (MSM) account for the majority of HIV/AIDS diagnoses
      and data suggest infection rates are rising. Identification of factors that
      increase the risk of infection is key to the development of effective prevention
      programs. Previous research has been inconsistent regarding the link between
      alcohol consumption and sexual risk taking among MSM. Daily reports of alcohol
      consumption and sexual behavior were completed for up to 30 days by 143 HIV
      negative MSM recruited online. This resulted in 2,887 daily reports of number of
      sex partners and 549 episodes of sex. Independent variables included age, number
      of standard drinks consumed, and partner type. Outcome variables included sex
      with a partner, a composite sexual risk variable, and unprotected anal
      intercourse (UAI). Alcohol consumption significantly increased the odds of having
      sex and had a significant positive association with the sexual risk composite
      variable. Age was a significant moderator of the association between alcohol
      consumption and sexual risk taking, with the effects of alcohol increasing with
      age. For example, at the 75%tile of age (37 years old), the odds of UAI increase
      from approximately 0.2 to 0.35 as the number of alcoholic drinks increases from
      zero to seven. Partner type did not have significant effects. Daily reports of
      alcohol consumption had a significant within-person association with sexual risk
      behaviors, particularly among older MSM. Findings highlight the importance of
      measuring individual differences as moderators of the association between alcohol
      and risky sexual behavior.

PMID- 18034300
TI  - Sperm chromatin stability and its relationship with fertilization rate after
      intracytoplasmic sperm injection (ICSI) in an assisted reproduction program.
AB  - OBJECTIVE: Evaluate sperm chromatin stability and its relationship with the rate
      of fertilization after procedures of intracytoplasmic sperm injection (ICSI) in a
      program of assisted reproduction. DESIGN: Prospective study. SETTING: Institute
      of Gynecology and Reproduction. PATIENTS: Thirty-three women with their
      respective partners (12 couples in the study group and 21 couples in the control
      group) participating in a program of assisted reproduction. The study group was
      defined as men with >30% of non-decondensed spermatozoa (high sperm chromatin
      stability). INTERVENTIONS: A part of each seminal sample was used to evaluate
      sperm chromatin stability under SDS and EDTA treatment and the second aliquot was
      used for the ICSI procedure. Fertilization was evaluated 16-18 h post sperm
      injection at a pronuclear stage. The fertilized oocytes were further cultured for
      24-48 h before transfer to the patient. MAIN OUTCOME MEASURES: Fertilization
      rate. RESULTS: Thirty-five oocytes (35.7%) in the group of study and 109 oocytes
      (78.9%) in the control group showed two pronuclei (P < 0.001). The coefficient of
      determination between the SDS + EDTA (Grade 2) and rate of fertilization was r
      (2) = 0.85 (P < 0.001) and the coefficient of regression was 1.72 +/- 0.19 (beta
      +/- ES) (P < 0.001). CONCLUSIONS: High sperm chromatin stability is a factor
      which reduces the rate of fertilization after ICSI procedure.

PMID- 18034301
TI  - Modulation of response timing in ADHD, effects of reinforcement valence and
      magnitude.
AB  - The present study investigated the impact of reinforcement valence and magnitude
      on response timing in children with ADHD. Children were required to estimate a 1
      s interval, and both the median response time (response tendency) and the
      intrasubject-variability (response stability) were investigated. In addition,
      heart rate and skin conductance were measured to examine the autonomic responses
      to reinforcement. Feedback-only trials were compared to low response cost trials
      (response cost for incorrect responses), low reward trials (reward for correct
      responses), high response cost and high reward trials. In feedback-only trials,
      children with ADHD underestimated more severely the interval and responded more
      variably than controls. Children with ADHD, unlike controls, were unaffected by
      the reinforcement conditions in terms of time underestimations. The variability
      of responding, on the other hand, decreased under conditions of reinforcement to
      a larger extent in children with ADHD than controls. There were no indications
      that children with ADHD were abnormally affected by the valence or magnitude of
      reinforcement. Furthermore, skin conductance responses increased when feedback
      was coupled with reinforcement, an effect which was larger in children with ADHD
      than controls. This could be interpreted as demonstrating that children with ADHD
      suffer from a diminished awareness of the significance of feedback in the
      feedback-only condition. The current study suggests that children with ADHD
      suffer from motivation problems when reinforcement was not available, at least
      when variability in responding was measured. Underestimations of time may reflect
      more stable deficits in ADHD.

PMID- 18034302
TI  - Alcohol use and congestive heart failure: incidence, importance, and approaches
      to improved history taking.
AB  - Alcohol use, abuse, and dependence have the potential to result in alcoholic
      cardiomyopathy (ACM). This distinct form of congestive heart failure (CHF) is
      responsible for 21-36% of all cases of nonischemic dilated cardiomyopathy in
      Western society. Without complete abstinence, the 4-year mortality for ACM
      approaches 50%. Therefore, accurate and detailed assessment of alcohol use in
      congestive heart failure is essential. The prevalence of problematic alcohol use
      is unrecognized by many clinicians. Clinical assessment of alcohol intake is
      often reduced to a simple question such as, "Do you drink?" Denial and
      minimization are hallmarks of alcohol abuse, with many individuals underreporting
      their use of alcohol. Clinicians can overcome these hurdles by implementing
      practical history taking measures to improve the accuracy of self-reported
      alcohol use. The data regarding the dangers of ongoing alcohol use in individuals
      with ACM make attempts to engage individuals in treatment to support abstinence
      essential. Suggestions for detailed and accurate assessment are discussed.

PMID- 18034299
TI  - Different ovarian stimulation protocols for women with diminished ovarian
      reserve.
AB  - PURPOSE: To review the available treatments for women with significantly
      diminished ovarian reserve and assess the efficacy of different ovarian
      stimulation protocols. METHODS: Literature research performed among studies that
      have been published in the Pubmed, in the Scopus Search Machine and in Cohrane
      database of systematic reviews. RESULTS: A lack of clear, uniform definition of
      the poor responders and a lack of large-scale randomized studies make data
      interpretation very difficult for precise conclusions. Optimistic data have been
      presented by the use of high doses of gonadotropins, flare up Gn RH-a protocol
      (standard or microdose), stop protocols, luteal onset of Gn RH-a and the short
      protocol. Natural cycle or a modified natural cycle seems to be an appropriate
      strategy. Low dose hCG in the first days of ovarian stimulation has promising
      results. Molecular biology tools (mutations, single nucleotide polymorphisms
      (SNPs)) have been also considered to assist the management of this group of
      patients. CONCLUSIONS: The ideal stimulation for these patients with diminished
      ovarian reserve remains a great challenge for the clinician, within the limits of
      our pharmaceutical quiver.

PMID- 18034303
TI  - Different effect of high fat diet and physical exercise in the hippocampal
      signaling.
AB  - Obesity is an epidemic disease that may affect brain function. The present study
      examined the effect of high fat diet (HF) and physical exercise on peripheral
      tissue and hippocampal signaling. CF-1 mice (n = 4, per cage) were divided into
      groups receiving high fat (HF) or control (CD) diets for 5 months, with or
      without voluntary exercise. Serum triacylglycerol, total cholesterol, HDLc, liver
      triacylglycerol and glycogen concentrations were evaluated (n = 6). Also, the
      phosphorylation state of the AKT --> ERK 1/2 --> CREB pathway (AKT, pAKTser473,
      ERK 1/2, pERK 1/2, CREB and pCREB, n = 4-6) was analyzed in the hippocampus. HF
      diet caused an increase in AKT phosphorylation at ser473 (P < 0.05), while
      exercise increased the phosphorylation of ERK 1/2 (P < 0.05) and CREB (P < 0.05).
      As expected, exercise reversed some of the harmful effects of HF, i.e., increased
      liver deposition of fat (P < 0.05) and fat gain in the abdominal region (P <
      0.05). In conclusion, the effects of exercise and HF diet on brain signaling
      appear to affect the hippocampal AKT --> ERK 1/2 --> CREB pathway in independent
      ways: HF intake caused increased phosphorylation of AKTser473, while exercise
      increased ERK 1/2 --> CREB signaling. The physiological relevance of these
      findings in brain function remains to be elucidated.

PMID- 18034304
TI  - Assessment and validation of the new capsule endoscopy Crohn's disease activity
      index (CECDAI).
AB  - BACKGROUND: Capsule endoscopy is a relatively new imaging tool for the detection
      of small bowel pathology. The assessment of the severity of Crohn's disease by
      capsule endoscopy is not standardized and is limited by interobserver variations
      in interpreting the findings. AIM: To develop, assess and validate a new, simple
      capsule endoscopy Crohn's disease activity index (CECDAI) in order to grade the
      severity of small bowel capsule endoscopy findings. METHODS: The system involves
      dividing the small bowel into proximal and distal segments according to transit
      time and then rating each segment on the basis of three parameters: inflammation
      (A), extent of disease (B) and presence of strictures (C). The segmental score is
      calculated by multiplying the inflammation subscore by the disease-subextent
      score and adding the stricture subscore (A x B + C); the final score is
      calculated by adding the two segmental scores: CECDAI = (A1 x B1 + C1) + (A2 x B2
      + C2). In the present study, four senior endoscopists (two with experience in
      capsule endoscopy interpretation) independently reviewed coded capsule endoscopy
      videos of 20 patients with Crohn's disease and rated them according to the
      CECDAI. Interobserver variability was analyzed by Spearman's correlation test.
      RESULTS: The CECDAI total scores for the 20 patients ranged from 0 to 26. The
      correlation for the total score assigned between every two observers was 0.867
      (0.700-1.000 = strong degree association; WHO classification; P < 0.0001). The
      Kappa statistics for agreement among all observers for the subscores and total
      scores were as follows: A1, 0.31 +/- 0.05; B1, 0.25 +/- 0.05; C1 (no cases); A2,
      0.51 +/- 0.05; B2, 0.57 +/- 0.05; C2, 0.27 +/- 0.07. All examiners reported that
      the system was simple to learn and apply. CONCLUSIONS: The CECDAI score may serve
      as a convenient, reliable and reproducible diagnostic and follow-up tool for use
      by experienced endoscopists in the evaluation of patients with Crohn's disease of
      the small bowel.

PMID- 18034305
TI  - Electroosmotic flow and particle transport in micro/nano nozzles and diffusers.
AB  - Micro/nano nozzles and diffusers have been used for ionic transport, drug and
      gene delivery. In this paper, a mathematical model is developed to simulate the
      electroosmotic flow (EOF) and particle transport in micro/nano nozzles/diffusers.
      The electrical potential and the flow field are investigated using the
      lubrication and the Debye-Huckel approximations specially for nanonozzles
      (overlapped electric double layers) and microdiffusers (thin EDLs) for which
      experimental results exist. The results show that a pressure field is induced by
      the presence of EDLs and the magnitude of this induced pressure is proportional
      to the ratio of the Debye length to the channel half-height. Embedded particles
      are often employed to illustrate the flow field and thus measure the local fluid
      velocity. The direction of particle motion is found to be dependent primarily on
      the particle charge and the wall charge. The calculated particle velocities
      compare well with experimental data.

PMID- 18034307
TI  - Primary sellar melanocytic tumor: report of new case and literature review.
AB  - CONTEXT: Primary sellar melanocytic tumors are extremely rare, and they can mimic
      hormonally inactive pituitary macroadenoma both clinically and radiologically.
      OBJECTIVES: The aim of this study was to describe a new case of primary sellar
      melanocytic tumor, and place it in the context of published literature. DESIGN:
      This is a case report. PATIENT: The case of a 61-year-old woman presenting with a
      2-month history of fatigue and progressive bitemporal hemianopia is described.
      Endocrine investigation revealed anterior pituitary insufficiency and
      hyperprolactinemia without diabetes insipidus. Magnetic resonance imaging
      demonstrated a sellar tumor mass with suprasellar extension compressing the optic
      chiasm, and intense gadolinium enhancement. Transsphenoidal surgical excision of
      the pituitary tumor was undertaken. Histological examination showed a melanocytic
      tumor. An extensive search failed to find evidence of any other primary or
      secondary site. Due to the presence of significant tumor residue at 3-month
      follow-up, another surgical resection was done followed by post-operative
      stereotactic radiotherapy of the sellar region. CONCLUSION: Primary sellar
      melanocytic tumors are exceptional lesions presenting most often as a tumor
      syndrome and/or anterior pituitary insufficiency mimicking a non-secreting
      pituitary macroadenoma. The management of these tumors consists of surgical
      removal of the tumor. However, surgery is often incomplete and stereotactic
      fractionated radiotherapy is frequently indicated.

PMID- 18034306
TI  - Dynamic testing in Cushing's syndrome.
AB  - Endogenous Cushing's syndrome (CS) results from chronic exposure to excess
      glucocorticoids. CS can be ACTH-dependent, caused by ACTH-secreting pituitary or
      ectopic tumours, or ACTH-independent, caused by cortisol-secreting adrenal
      tumours. CS can be an extremely difficult diagnosis to make, and assessment will
      include clinical, biochemical and radiological evaluation. Several screening
      tests are used for the confirmation of hyper-cortisolaemia and its
      differentiation from other, more frequent, clinical abnormalities, such as simple
      obesity, hypertension, depression etc. Other dynamic tests are useful for
      establishing the aetiology. We have reviewed the current literature on the
      diagnosis of CS, and based on these data and our own experience, suggest the most
      useful tests and diagnostic criteria to be used. We conclude that even though
      laboratory testing is a fundamental part of the investigation of patients with
      CS, the interpretation of the tests should always be performed with extreme care,
      as none of the tests has proven fully capable of distinguishing all cases of CS.
      The biochemical results should be interpreted jointly with the clinical aspects
      and the radiology findings in a probabilistic matrix, and not as part of a
      uniform algorithm.

PMID- 18034308
TI  - An ethanol-tolerant recombinant Escherichia coli expressing Zymomonas mobilis pdc
      and adhB genes for enhanced ethanol production from xylose.
AB  - An ethanol-tolerant mutant, ET1, was isolated by an enrichment method from
      Escherichia coli JM109. Strains JM109 and ET1 were transformed with expression
      vector pZY507bc containing Zymomonas mobilis alcohol dehydrogenase II (adhB) and
      pyruvate decarboxylase (pdc) genes, resulting in an ethanol-sensitive recombinant
      strain JMbc and an ethanol-tolerant recombinant strain, ET1bc. Alcohol
      dehydrogenase and pyruvate decarboxylase activities were 24 and 32% lower,
      respectively, in JMbc than in ET1bc. ET1bc fermented 10% (w/v) xylose to give
      39.4 g ethanol/l (77%, theoretical yield), a 1.3-fold increase compared with the
      ethanol-sensitive strain JMbc.

PMID- 18034309
TI  - Protein-ligand docking with multiple flexible side chains.
AB  - In this work, we validate and analyze the results of previously published cross
      docking experiments and classify failed dockings based on the conformational
      changes observed in the receptors. We show that a majority of failed experiments
      (i.e. 25 out of 33, involving four different receptors: cAPK, CDK2, Ricin and
      HIVp) are due to conformational changes in side chains near the active site. For
      these cases, we identify the side chains to be made flexible during docking
      calculation by superimposing receptors and analyzing steric overlap between
      various ligands and receptor side chains. We demonstrate that allowing these side
      chains to assume rotameric conformations enables the successful cross docking of
      19 complexes (ligand all atom RMSD < 2.0 A) using our docking software FLIPDock.
      The number of side receptor side chains interacting with a ligand can vary
      according to the ligand's size and shape. Hence, when starting from a complex
      with a particular ligand one might have to extend the region of potential
      interacting side chains beyond the ones interacting with the known ligand. We
      discuss distance-based methods for selecting additional side chains in the
      neighborhood of the known active site. We show that while using the molecular
      surface to grow the neighborhood is more efficient than Euclidian-distance
      selection, the number of side chains selected by these methods often remains too
      large and additional methods for reducing their count are needed. Despite these
      difficulties, using geometric constraints obtained from the network of bonded and
      non-bonded interactions to rank residues and allowing the top ranked side chains
      to be flexible during docking makes 22 out of 25 complexes successful.

PMID- 18034310
TI  - Computational study on mechanism of G-quartet oligonucleotide T40214 selectively
      targeting Stat3.
AB  - The mounting evidences have shown that signal transducer and activator of
      transcription 3 (Stat3) is a critical target for cancer therapy. Recently, we
      developed a G-quartet oligonucleotide T40214 as a novel and potent Stat3
      inhibitor. T40214 specifically inhibited DNA-binding activity of Stat3 and
      significantly suppressed the growth of many tumor xenografts in nude mice. To
      determine the mechanism of GQ-ODNs selectively targeting Stat3, we established a
      3D model of complex T40214/p-Stat3 dimer based on experimental evidences. The
      binding site of T40214 within Stat3 dimer was determined by statistical docking
      analysis. The results indicated that T40214 strongly interacted within the region
      from residue E638 through E652 of Stat3 dimer. The binding model refined by Hex
      docking disclosed that T40214 binds to SH2 domain of Stat3 and forms H-bonds with
      residues Q643, Q644, N646, and N647, which are critical for the binding
      interaction. The 3D models also suggested that T40214 inhibits Stat3 activity
      through disrupting the binding interaction between Stat3 dimer and DNA duplex for
      transcription. Our computational studies provided a platform for future structure
      based drug design of novel Stat3 inhibitors.

PMID- 18034311
TI  - Generation of in-silico cytochrome P450 1A2, 2C9, 2C19, 2D6, and 3A4 inhibition
      QSAR models.
AB  - In-silico models were generated to predict the extent of inhibition of cytochrome
      P450 isoenzymes using a set of relatively interpretable descriptors in
      conjunction with partial least squares (PLS) and regression trees (RT). The
      former was chosen due to the conservative nature of the resultant models built
      and the latter to more effectively account for any non-linearity between
      dependent and independent variables. All models are statistically significant and
      agree with the known SAR and they could be used as a guide to P450 liability
      through a classification based on the continuous pIC50 prediction given by the
      model. A compound is classified as having either a high or low P450 liability if
      the predicted pIC(50) is at least one root mean square error (RMSE) from the
      high/low pIC(50) cut-off of 5. If predicted within an RMSE of the cut-off we
      cannot be confident a compound will be experimentally low or high so an
      indeterminate classification is given. Hybrid models using bulk descriptors and
      fragmental descriptors do significantly better in modeling CYP450 inhibition,
      than bulk property QSAR descriptors alone.

PMID- 18034312
TI  - Identification and localisation of the rice nicotianamine aminotransferase gene
      OsNAAT1 expression suggests the site of phytosiderophore synthesis in rice.
AB  - Rice plants (Oryza sativa L.) take up iron using iron-chelating compounds known
      as mugineic acid family phytosiderophores (MAs). In the biosynthetic pathway of
      MAs, nicotianamine aminotransferase (NAAT) catalyses the key step from
      nicotianamine to the 3''-keto form. In the present study, we identified six rice
      NAAT genes (OsNAAT1-6) by screening a cDNA library made from Fe-deficient rice
      roots and by searching databases. Among the NAAT homologues, OsNAAT1 belongs to a
      subgroup containing barley functional NAAT (HvNAAT-A and HvNAAT-B) as well as a
      maize homologue cloned by cDNA library screening (ZmNAAT1). Northern blot and RT
      PCR analysis showed that OsNAAT1, but not OsNAAT2-6, was strongly up-regulated by
      Fe deficiency, both in roots and shoots. The OsNAAT1 protein had NAAT enzyme
      activity in vitro, confirming that the OsNAAT1 gene encodes functional NAAT.
      Promoter-GUS analysis revealed that OsNAAT1 was expressed in companion and
      pericycle cells adjacent to the protoxylem of Fe-sufficient roots. In addition,
      expression was induced in all cells of Fe-deficient roots, with particularly
      strong GUS activity evident in the companion and pericycle cells. OsNAAT1
      expression was also observed in the companion cells of Fe-sufficient shoots, and
      was clearly induced in all the cells of Fe-deficient leaves. These expression
      patterns highly resemble those of OsNAS1, OsNAS2 and OsDMAS1, the genes
      responsible for MAs biosynthesis for Fe acquisition. These findings strongly
      suggest that rice synthesizes MAs in whole Fe-deficient roots to acquire Fe from
      the rhizosphere, and also in phloem cells to maintain metal homeostasis
      facilitated by MAs-mediated long-distance transport.

PMID- 18034313
TI  - Reme1, a Copia retrotransposon in melon, is transcriptionally induced by UV
      light.
AB  - For the first time, numerous sequences of Copia and Gypsy retrotransposons from
      the Cucumis melo genome have been obtained and analyzed. Phylogenetic analyses of
      sequences of both types of long terminal repeat (LTR) retrotransposons were
      carried out. The melon genome contains approximately 20,000 Gypsy and 6,800 Copia
      elements, comprising about 26% of its total size. Starting from a retrotransposon
      fragment, we have cloned and characterized an entire melon retrotransposon, named
      Reme1, which is 5,149 bp long. Reme1 belongs to the Superfamily Copia
      retrotransposons by its protein domain order and sequence similarity to other
      Copia elements of dicotyledons. The haploid genome of melon (var. "Piel de Sapo")
      contains about 120 copies of Reme1. Several copies of Reme1 are transcriptionally
      active, although at low levels, in melon leaves as analyzed by reverse
      transcription PCR (RT-PCR) and sequencing. However, the transcript pool is
      considerably increased when melon leaves are treated with UV light, as has been
      seen for various retroelements in many organisms. The cDNAs of Reme1 transcripts
      showed less diversity than do Reme1 genomic sequences, suggesting that a
      subfamily of these elements is differentially responsive to UV.

PMID- 18034314
TI  - PsRBR1 encodes a pea retinoblastoma-related protein that is phosphorylated in
      axillary buds during dormancy-to-growth transition.
AB  - In intact plants, cells in axillary buds are arrested at the G1 phase of the cell
      cycle during dormancy. In mammalian cells, the cell cycle is suppressed at the G1
      phase by the activities of retinoblastoma tumor suppressor gene (RB) family
      proteins, depending on their phosphorylation state. Here, we report the isolation
      of a pea cDNA clone encoding an RB-related protein (PsRBR1, Accession No.
      AB012024) with a high degree of amino acid conservation in comparison with RB
      family proteins. PsRBR1 protein was detected as two polypeptides using an anti
      PsRBR1 antibody in dormant axillary buds, whereas it was detected as three
      polypeptides, which were the same two polypeptides and another larger polypeptide
      2 h after terminal decapitation. Both in vitro-synthesized PsPRB1 protein and
      lambda protein phosphatase-treated PsRBR1 protein corresponded to the smallest
      polypeptide detected by anti-PsRBR1 antibody, suggesting that the three
      polypeptides correspond to non-phosphorylated form of PsRBR1 protein, and lower-
      and higher-molecular mass forms of phosphorylated PsRBR1 protein. Furthermore, in
      vivo labeling with [32P]-inorganic phosphate indicated that PsRBR1 protein was
      more phosphorylated before mRNA accumulation of cell cycle regulatory genes such
      as PCNA. Together these findings suggest that dormancy-to-growth transition in
      pea axillary buds is regulated by molecular mechanisms of cell cycle control
      similar to those in mammals, and that the PsRBR1 protein has an important role in
      suppressing the cell cycle during dormancy in axillary buds.

PMID- 18034315
TI  - Detoxification of olive mill wastewaters by Moroccan yeast isolates.
AB  - A total of 105 yeast strains were isolated from Moroccan olive oil production
      plants and evaluated for their ability to grow in olive oil mill wastewaters
      (OMW). The 9 isolates that grew best on OMW were selected for further study to
      evaluate their effect on removal of organic pollutants and OMW phytotoxicity
      (barley seed germination test). The results showed that at least four yeast
      isolates effectively lowered the toxicity of this effluent in addition to
      providing very useful materials in terms of both yeast biomass (6 g/l DW) and an
      irrigation fluid. This group of yeast isolates significantly reduced the
      concentration of total phenols (44% removal) and Chemical Oxygen Demand, COD (63%
      removal). The best germination rate of 80% for undiluted OMW was obtained for
      strain Candida holstii that also increased the pH from 4.76 to 6.75. Principal
      component analysis of the results obtained for the best yeast strains confirmed
      the importance of COD and total phenol reduction along with increase of organic
      nitrogen and final pH for the improvement of germination rates and phytotoxic
      reduction. This study has highlighted the potential of indigenous yeasts in
      detoxification of olive mill wastewaters.

PMID- 18034316
TI  - Tissue distribution of quiescin Q6/sulfhydryl oxidase (QSOX) in developing mouse.
AB  - Quiescin Q6/sulfhydryl oxidases (QSOX) are revisited thiol oxidases considered to
      be involved in the oxidative protein folding, cell cycle control and
      extracellular matrix remodeling. They contain thioredoxin domains and introduce
      disulfide bonds into proteins and peptides, with the concomitant hydrogen
      peroxide formation, likely altering the redox environment. Since it is known that
      several developmental processes are regulated by the redox state, here we
      assessed if QSOX could have a role during mouse fetal development. For this
      purpose, an anti-recombinant mouse QSOX antibody was produced and characterized.
      In E(13.5), E(16.5) fetal tissues, QSOX immunostaining was confined to mesoderm-
      and ectoderm-derived tissues, while in P1 neonatal tissues it was slightly
      extended to some endoderm-derived tissues. QSOX expression, particularly by
      epithelial tissues, seemed to be developmentally-regulated, increasing with
      tissue maturation. QSOX was observed in loose connective tissues in all stages
      analyzed, intra and possibly extracellularly, in agreement with its putative role
      in oxidative folding and extracellular matrix remodeling. In conclusion, QSOX is
      expressed in several tissues during mouse development, but preferentially in
      those derived from mesoderm and ectoderm, suggesting it could be of relevance
      during developmental processes.

PMID- 18034317
TI  - Screening of AMP-activated protein kinase alpha2 subunit interacting proteins by
      bacterial two-hybrid system.
AB  - AMP-activated protein kinase (AMPK) is a ubiquitous eukaryotic protein kinase
      regulating cellular metabolism and energy demand. In brain AMPK plays a role as a
      multidimensional energy sensor and AMPK alpha2 subunit is expressed at higher
      levels than AMPK alpha1 subunit. In order to identify potential targets of AMPK
      in brain, we perform bacterial two-hybrid screening of a rat fetal brain cDNA
      library using AMPK alpha2 subunit as bait. Here, we present seven potential AMPK
      alpha2 subunit interacting proteins, including 6-phosphofructo-1-kinase (PFK-1),
      polyubiquitin, cytochrome c oxidase subunit I (COX I), heat shock protein 8
      (HSP8), HLA-B-associated transcript 3 (BAT3) isoform 1, protein tyrosine
      phosphatase receptor type D (PTPRD) and islet-brain 1 (IB1). They are involved in
      glycolysis, protein degradation, mitochondrial electron transport and apoptosis
      pathways participating in energy regulation directly or indirectly. These data
      may provide new insight into further studying the pathways of AMPK energy
      regulation in brain and possible mechanisms of AMPK-mediated neuroprotective
      effect.

PMID- 18034318
TI  - Characterization of a male sterile related gene BcMF15 from Brassica campestris
      ssp. chinensis.
AB  - Data from cDNA-AFLP analysis based on the genome-wide transcriptional profiling
      on the flower buds of the male meiotic cytokinesis (mmc) mutant and its wild-type
      of Brassica campestris L. ssp. chinensis Makino, syn. B. rapa L. ssp. chinensis,
      indicated that mutation of the MMC gene resulted in changes in expression of a
      variety of genes. A transcript-derived fragment specifically accumulated in the
      wild-type flower buds was isolated, and the corresponding full-length cDNA and
      DNA was subsequently amplified. Bioinformatical analyses of this gene named
      BcMF15 (GenBank accession number EF600901) showed that it encoded a protein with
      103 amino acids. The BcMF15 had a 88% nucleotide similarity to a lipid transfer
      protein-like gene. Moreover, sequence prediction indicated that BcMF15 might
      encode a membrane protein with a signal peptide at the N-terminus. Meanwhile, six
      domains were predicted in the deduced BcMF15 protein, such as the AAI domain
      existing in some crucial proteins of pollen development-preferential, signal
      peptide, transmembrane domain, vWF domain, ZnF_C4 domain, and Tryp_alpha_amyl
      domain. Spatial and temporal expression patterns analysis by RT-PCR indicated
      that BcMF15 was exclusively expressed in the fertile line, which indicated this
      gene is male sterile related. Phylogenetic analysis in Cruciferae revealed that
      the BcMF15 was relative conservative in evolution. We suppose BcMF15 may be a
      critical molecule in the transmembrane transportation and signal transduction
      during microspore development.

PMID- 18034319
TI  - Coping, meaning in life, and quality of life in congestive heart failure
      patients.
AB  - OBJECTIVE: The present study examined (1) whether particular coping strategies
      used to deal with congestive heart failure (CHF) are related to meaning in life
      across time, and (2) whether meaning in life mediates the effect of coping on
      health-related quality of life. METHODS: A sample of 155 CHF patients received
      questionnaire packets at two time points, 6 months apart. Main outcome measures
      included Meaning in Life and Mental and Physical Health-Related Quality of Life
      (HRQOL). RESULTS: Coping (particularly acceptance/positive reinterpretation and
      religious coping) was not only related to meaning in life, but also to increased
      meaning over time. Further, meaning in life was related to both mental and
      physical components of HRQOL. However, coping was minimally related to HRQOL and
      its effects were not mediated by meaning in life. CONCLUSIONS: These results add
      to accumulating evidence that life meaning is important in the context of living
      with a chronic, life-threatening illness. Further, coping--especially acceptance
      and religious coping--is related to increased life meaning over time in the
      context of life limiting illness.

PMID- 18034320
TI  - The CLE family of plant polypeptide signaling molecules.
AB  - Polypeptide ligands have long been recognized as primary signaling molecules in
      diverse physiological processes in animal systems. Recent studies in plants have
      provided major breakthroughs with the discovery that small polypeptides are also
      involved in many plant biological processes, indicating that the use of
      polypeptides as signaling molecules in cell-to-cell communication is
      evolutionarily conserved. The CLAVATA3 (CLV3)/ENDOSPERM SURROUNDING REGION (ESR)
      related (CLE) proteins are currently the best understood family of small
      polypeptides in plants. The recent isolation of MCLV3 from Arabidopsis and TDIF
      from a Zinnia cell culture system indicates that biologically active CLE
      polypeptides are produced by post-translational proteolysis and modification,
      similar to peptide hormone production in animals and yeast. Here, we review
      exciting discoveries involving the identification of the CLE proteins and their
      functions in various aspects of plant development, including restriction of stem
      cell accumulation by CLV3 and inhibition of xylem differentiation by TDIF.

PMID- 18034321
TI  - We find them here, we find them there: functional bacterial amyloid.
AB  - Protein amyloid is often deposited in connection with neurodegenerative diseases.
      Such deposits generally possess three principal drawbacks: cytotoxicity, lack of
      spatial control in their deposition and structural polymorphism. These are
      typical features of biologically non-optimized systems which have not been
      exposed to evolutionary pressure. Nevertheless, Nature uses the cross-beta self
      organizing principle in many structural contexts where a strong but pliable
      material is needed. Functional amyloid is found in humans, invertebrates, fungi
      and, not least, bacteria, in which amyloid may be the rule rather than the
      exception. Detailed case studies reveal how directed nucleation can use tailor
      made proteins optimized to assume a specific amyloid conformation, leading to
      remarkably robust assemblies. This makes it highly challenging to purify and
      analyze the products formed in vivo. We contrast pathogenic and in-vitro-formed
      amyloid with functional amyloid, paying particular reference to bacterial
      amyloid, and discuss challenges and perspectives in identifying and
      characterizing this class of protein.

PMID- 18034322
TI  - The helicase-like transcription factor and its implication in cancer progression.
AB  - The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of
      chromatin-remodeling factors. Several SWI/SNF genes are disrupted in cancer,
      suggesting their possible role as tumor suppressors. Similarly, the HLTF gene was
      found to be inactivated by hypermethylation in a significant number of colon,
      gastric and uterine tumors, indicating that HLTF silencing may confer a growth
      advantage and that HLTF could be considered as a tumor suppressor gene. However,
      20-fold HLTF overexpression was detected in various transformed cell lines,
      suggesting that HLTF could be associated with neoplastic transformation and act
      more like an oncogene. Moreover, HLTF activation was recently linked to the
      initial steps of carcinogenesis in an experimental model of estrogen-induced
      kidney tumors. Those apparently contradictory observations suggest that HLTF
      might play various roles in cancer. In this review, we will try to reconcile all
      these data in order to specify the role of HLTF in cancer progression.

PMID- 18034323
TI  - Cost and occurrence of thrombocytopenia in patients receiving venous
      thromboembolism prophylaxis following major orthopaedic surgeries.
AB  - BACKGROUND: Many factors impact the choice of anticoagulant used for venous
      thromboembolism prophylaxis following orthopaedic surgery. Thrombocytopenia (TCP)
      is an important factor from both clinical and economic perspectives, warranting
      assessment between the available agents. Thus, a retrospective cohort analysis
      was conducted to: (1) report the occurrence of TCP in a treatment and no
      treatment group, (2) evaluate the impact of anticoagulant choice on TCP within
      the treatment group, and (3) assess the clinical and economic implications of TCP
      in the treatment group. METHODS: Administrative claims from a hospital database
      were used to identify patients with hip replacement, knee replacement, or hip
      fracture surgery. The treatment group (n = 144,806) included patients receiving
      one of the following injectable anticoagulants post-operatively: dalteparin (n =
      16,109); enoxaparin (n = 97,827); fondaparinux (n = 12,532); or unfractionated
      heparin (UFH) (n = 18,338). The no treatment group consisted of patients who did
      not receive one of the four injectable anticoagulants (n = 112,574) post
      operatively. Outcomes were assessed for the hospitalization period plus 2 months
      post-discharge while controlling for relevant demographic and clinical
      characteristics. RESULTS: The occurrence of TCP was 1.0% in the no treatment
      group and 1.7% in the treatment group. Within the treatment group, patients who
      received dalteparin, enoxaparin, and UFH were significantly more likely to
      experience coded thrombocytopenia than those in the no treatment group. The risk
      of TCP among patients who received fondaparinux was not significantly different
      from the no treatment cohort (odds ratio [OR] = 1.15, 95% CI: 0.96-1.37, P =
      0.13). Patients in the treatment group with coded TCP had 22% higher adjusted
      mean total healthcare costs (relative cost difference) compared to those without
      ($19,134 vs. $15,400, respectively, P < 0.0001), greater mean length of stay
      (LOS) (8.4 vs. 5.7, respectively), and a greater likelihood of experiencing a
      venous thromboembolic (VTE) event (6.1% vs. 2.4%, respectively). CONCLUSION:
      Patients treated with fondaparinux did not have a significant increase in the
      risk of TCP compared to patients not on prophylaxis. In contrast, the risk was
      increased in those treated with enoxaparin, dalteparin, and UFH compared to the
      patients not on prophylaxis. Patients in the treatment group with coded TCP
      experienced more thrombotic events, incurred greater per patient healthcare
      costs, and experienced longer LOS than patients without coded TCP. Therefore, the
      risk of TCP should be considered when evaluating the profile of injectable
      anticoagulants since TCP may have important clinical and economic implications.

PMID- 18034324
TI  - Association of the single-nucleotide polymorphism and haplotype of the P-selectin
      gene with ischemic stroke.
AB  - Inflammation has recently proven to be associated with the pathogenesis of
      atherosclerosis and inflammatory genes are good candidates for the risk of
      developing atherosclerosis. The early phase of atherosclerosis involves the
      recruitment of inflammatory cells from the circulation and their transendothelial
      migration. This process is mainly mediated by cellular adhesion molecules. The
      adhesion molecule P-selectin may play a role in the pathogenesis of
      atherosclerosis. Polymorphism of P-selectin gene, which may affect the production
      level of the adhesion molecule, has been associated with a number of
      atherosclerotic disease. To test this hypothesis, we investigated the
      relationship of P-selectin gene polymorphisms and ischemic stroke in a Chinese
      population. We analyzed single nucleotide polymorphisms of P-selectin gene -2,123
      G/C, -1,969 G/A, -1,817 T/C and Thr715Pro in three hundred and five patients with
      ischemic stroke and 280 age and sex matched controls, using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing
      method. There were no significant differences in the genotype, allele and
      haplotype frequencies of P-selectin gene polymorphisms between the group of
      patients with ischemic stroke and the control group. Furthermore, there was no
      significant association of genotype, allele and haplotype at any of the
      polymorphism in relation to any subtype of ischemic stroke. We did not observe an
      association between P-selectin gene polymorphisms and ischemic stroke or any
      subtype of ischemic stroke. However, further studies are needed to explore the
      complex interaction between environmental factors and P-selectin gene
      polymorphisms in the risk of ischemic stroke, particularly in ethnically
      different populations.

PMID- 18034325
TI  - Can a violation of investor trust lead to financial contagion in the market for
      tax-exempt hospital bonds?
AB  - Not-for-profit hospitals rely heavily on tax-exempt debt. Investor confidence in
      such instruments was shaken by the 1998 bankruptcy of the Allegheny Health and
      Education Research Foundation (AHERF), which was the largest U.S. not-for-profit
      failure up to that date and whose default was accompanied by claims of accounting
      irregularities. Such shocks can result in contagion whereby all hospitals are
      viewed as riskier. We test for the significance and duration of resulting
      contagion using an industry-specific model of interest cost determinants.
      Empirical tests indicate that contagion does occur, resulting in higher interest
      on new debt issues from other hospitals.

PMID- 18034326
TI  - Wireless capsule endoscopy indication as a predictor of study quality.
AB  - PURPOSE: The aim of the study was to assess whether specific indications are
      associated with poor visualization during wireless capsule endoscopy (WCE)
      studies . Four hundred consecutive WCE studies performed at our institute were
      analyzed retrospectively. RESULTS: Data was available on cases involving 176
      males and 224 females. About 23 capsules failed to exit the stomach (excluded
      from the study). Poor visualization was reported in 66 (17%) WCE studies. The
      most common indications were gastrointestinal (GI) blood loss (271 cases; 72%),
      abdominal pain and/or diarrhea (73 cases; 19%), and suspected inflammatory bowel
      disease (46 cases; 12%). Of the 271 patients suffering GI bleeding, visualization
      was reported to be poor in 53 (19%) patients; among those showing other
      indications, visualization was poor in 13 (11%) patients (P = 0.02). After
      controlling for secondary indications and age, GI bleeding was associated with a
      higher rate of poor visualization compared to all other indications (odds ratio
      2.6; 95% confidence interval 1.4-6.8). CONCLUSIONS: Gastrointestinal bleeding as
      study indication for WCE is associated with a higher rate of poor visualization.

PMID- 18034327
TI  - Identification of a cluster IV pleiotropic drug resistance transporter gene
      expressed in the style of Nicotiana plumbaginifolia.
AB  - ATP-binding cassette transporters of the pleiotropic drug resistance (PDR)
      subfamily are composed of five clusters. We have cloned a gene, NpPDR2, belonging
      to the still uncharacterized cluster IV from Nicotiana plumbaginifolia. NpPDR2
      transcripts were found in the roots and mature flowers. In the latter, NpPDR2
      expression was restricted to the style and only after pollination. A 1.5-kb
      genomic sequence containing the putative NpPDR2 transcription promoter was fused
      to the beta-glucuronidase reporter gene. The GUS expression pattern confirmed the
      RT-PCR results that NpPDR2 was expressed in roots and the flower style and showed
      that it was localized around the conductive tissues. Unlike other PDR genes,
      NpPDR2 expression was not induced in leaf tissues by none of the hormones
      typically involved in biotic and abiotic stress response. Moreover, unlike NpPDR1
      known to be involved in biotic stress response, NpPDR2 expression was not induced
      in the style upon Botrytis cinerea infection. In N. plumbaginifolia plants in
      which NpPDR2 expression was prevented by RNA interference, no unusual phenotype
      was observed, including at the flowering stage, which suggests that NpPDR2 is not
      essential in the reproductive process under the tested conditions.

PMID- 18034328
TI  - [Induction of anaesthesia in the child with a full stomach].

PMID- 18034329
TI  - What is life? On Erwin Schrodinger, his cat, and the Journal of Molecular
      Medicine.

PMID- 18034330
TI  - [Combined therapies including interventional radiology].
AB  - Interventional tumor therapies are a therapeutic option that is increasingly
      applied in the treatment of malignant diseases. Thermoablation of primary and
      secondary liver tumors is the most widely used of them, and owing to the
      promising results it has given, it is becoming an increasingly well-accepted
      treatment procedure. These interventional radiological tumor therapies must be
      evaluated in comparison with standard therapies, and particularly in comparison
      with surgical resection, radiotherapy, and systemic chemotherapy. This
      comparative approach to the evaluation of different therapies is reflected in the
      current literature. Besides this approach, interdisciplinary combination of
      therapies is a promising approach to the optimization of oncological therapy
      strategies. Local thermoablation in association with systemic or local
      chemotherapy, and surgical resection in association with thermoablation are
      interdisciplinary therapy concepts that expand the range of therapeutic options
      available. Against this backdrop, studies to evaluate interventional tumor
      therapies as part of interdisciplinary combination therapies are necessary.

PMID- 18034331
TI  - [Botulinum toxin for the treatment of overactive bladder--an overview].
AB  - This article shall give a state-of-the-art review about the treatment of
      neurogenic and idiopathic detrusor overactivity with botulinum toxin injections
      into the detrusor muscle. We searched PubMed for original articles up to December
      2006. Abstracts published at international congresses were also considered if
      they provided substantial new information. Based on this review it appears that a
      majority of patients with spinal cord injury regains continence after botulinum
      toxin A injection and that in children with myelomeningocele a significant
      improvement in continence can also be achieved. A concomitant reduction of
      intravesical pressure protects the upper urinary tract in these patients. In
      idiopathic detrusor overactivity, injection of botulinum toxin A also resulted in
      improvement of continence and reduction of daily micturition frequency. For both
      indications a high success rate could be achieved with an average duration of the
      effect of 6 months. Repeated injections into the detrusor seem to have no adverse
      effects in terms of duration or strength of the effect. Side effects were
      marginal and systemic side effects were experienced only in individual cases; in
      some patients with idiopathic detrusor overactivity intermittent self
      catheterization was required. Overall intradetrusor injections of botulinum toxin
      seem to be a new, highly effective, and safe alternative in the treatment of
      neurogenic and idiopathic detrusor overactivity.

PMID- 18034332
TI  - Radiological evaluation of the proximal tibiofibular joint in knees with severe
      primary osteoarthritis.
AB  - The proximal tibiofibular joint (PTFJ) can be considered to be the fourth
      compartment of knee joint. Although degenerative diseases of the knee joint may
      also have detrimental effects on the PTFJ until now, details of arthritic
      affection of PTFJ in the elderly who have severe femorotibial arthritis have not
      been described. Convenience samples of knees of elderly patients with Kellgren
      Lawrence grade III-IV primary osteoarthritis were investigated further in order
      to determine the X-ray findings of PTFJ. Sixty knees in 34 patients with an
      average age of 71 years (61-86 years) were examined. Both knees were examined in
      26 patients. On the radiographs, 23 joints were grade IV, 14 were grade III, and
      23 were grade II. At most, only minor differences were seen between knees on the
      same patient in terms of lower extremity alignment, grade of TFJ degeneration,
      grade of PTFJ degeneration, and type of PTFJ. Interobserver correlation was good
      for radiographic evaluation of PTFJ (kappa = 0.557). By intraobserver analysis
      with McNemar test, there was no statistically significant difference between the
      radiographic evaluations of PTFJ (p = 0.167). Arthritic grades of PTFJ and
      tibiofemoral joints were strongly correlated (Pearson coefficient r = 0.58, p <
      0.001). No significant relation was found between type of PTFJ and grade of
      arthritis (chi(2) test, p = 0.42). In the light of these findings, the proximal
      tibiofibular joint should be evaluated for arthritic findings that may be
      responsible for lateral knee pain before a total knee arthroplasty operation is
      considered. The type of PTFJ is not related to the degree of this joint
      arthritis.

PMID- 18034333
TI  - Self-efficacy of knee function as a pre-operative predictor of outcome 1 year
      after anterior cruciate ligament reconstruction.
AB  - The knee self-efficacy scale (K-SES) has been shown to have good reliability,
      validity and responsiveness during rehabilitation for patients' perceived self
      efficacy of knee function. Determinants of self-efficacy of knee function 1 year
      after ACL reconstruction have been found to be the patients' internal locus of
      control and knee symptoms in sports and recreation. The predictive ability of
      perceived self-efficacy of knee function measured by the K-SES has not been
      studied in terms of patient outcome after an ACL reconstruction. The purpose of
      this study was to explore the potential for pre-operative self-efficacy of knee
      function measured by the K-SES to predict patient outcome in terms of physical
      activity, knee symptoms and muscle function 1 year after an ACL reconstruction.
      Thirty-eight patients were evaluated for outcome in terms of physical activity
      with the Tegner activity scale and the physical activity scale (PAS), knee
      symptoms with the Lysholm knee scoring scale and the knee injury and
      osteoarthritis outcome score (KOOS) and knee function with ability tests for
      muscle function 1 year after ACL reconstruction. Multiple regression and logistic
      multiple regression analysis were used to evaluate the K-SES as a possible
      predictor of outcome. The patients' present perceived self-efficacy of knee
      function (K-SES(Present)) pre-operatively was a significant predictor (P = 0.016)
      of the patients returning to their intensity and frequency of physical activity
      (PAS) 1 year after ACL reconstruction, when adjusted for age, gender and pre
      injury physical activity level (Tegner(Pre-injury)) (odds ratio = 2.1). The
      patients' perceived future self-efficacy of knee function (K-SES(Future)) pre
      operatively was a significant predictor (P = 0.045) of their self-rated knee
      function in sports/recreational activities (KOOS(Sports/recreation)) at the 1
      year follow-up, when adjusted for age, gender and Tegner(Pre-injury )(R (2
      )=0.25). The pre-operative K-SES(Future) was also a significant predictor (P =
      0.023) of the patients' knee-related quality of life (KOOS(Qol)), at the 1-year
      follow-up, when adjusted for age, gender and Tegner(Pre-injury) (R (2 )=0.23).
      The pre-operative K-SES(Future) was furthermore a significant predictor of an
      acceptable outcome 1 year after surgery, on the Lysholm knee scoring scale (P =
      0.003, odds ratio = 1.7), as well as on KOOS(Sports/recreation) (P = 0.002, odds
      ratio = 1.6) and knee-related quality of life (KOOS(Qol)) (P = 0.037, odds ratio
      = 1.4), when adjusted for age, gender and Tegner(Pre-injury). The pre-operative K
      SES(Future) was also a significant predictor (P = 0.04) of an acceptable outcome
      1 year after surgery, on the one-leg hop for distance (odds ratio = 2.2), when
      adjusted for age, gender and Tegner(Pre-injury). In conclusion, this study
      indicates that patients' perceived self-efficacy of knee function pre-operatively
      is of predictive value for their return to acceptable levels of physical
      activity, symptoms and muscle function 1 year after ACL reconstruction.

PMID- 18034334
TI  - Species differences in 3-methylsulphonyl-DDE bioactivation by adrenocortical
      tissue.
AB  - The CYP11B1-activated adrenocortical toxicant 3-methylsulphonyl-DDE (3-MeSO2-DDE)
      is proposed as a lead compound for an improved chemotherapy for adrenocortical
      carcinoma. We compared the binding of 3-MeSO2-[14C]DDE in the adrenal cortex of
      four rodent species; hamster, guinea pig, mouse and rat, using a precision-cut
      adrenal slice culture system ex vivo. Localization and quantification of the
      bound radioactivity were carried out using light microscopy autoradiography and
      radioluminography. The results revealed major species differences since 3-MeSO2
      [14C]DDE was extensively bound to the hamster adrenal tissue while the guinea pig
      adrenals were devoid of binding. A high binding in mouse adrenal cortex was
      confirmed while binding in rat adrenal cortex was very weak. The results support
      previous observations that metabolic activation of 3-MeSO2-DDE is highly species
      dependent. Since CYP11B1 could be expressed in tissues other than the adrenal
      cortex, final toxicological characterization should be carried out in a species
      that can bioactivate this compound.

PMID- 18034335
TI  - The activation of transient receptor potential vanilloid receptor subtype 1 by
      capsaicin without extracellular Ca2+ is involved in the mechanism of distinct
      substance P release in cultured rat dorsal root ganglion neurons.
AB  - Using a highly sensitive substance P (SP) radioimmunoassay, we attempted to
      elucidate the molecular mechanism of SP release from cultured adult rat dorsal
      root ganglion (DRG) neurons triggered by capsaicin. As a result, we found that
      capsaicin can induce SP release in the absence of extracellular Ca2+ by
      activating transient receptor potential vanilloid receptor subtype 1 (TRPV1).
      Therefore, we compared the pharmacological profile of SP release involved in
      several intracellular effectors (phosphoinositide 3-kinase (PI3K), Ca2+ release
      from intracellular stores, and mitogen-activated protein (MAP) kinases) in the
      presence/absence of extracellular Ca2+ by stimulating DRG neurons with various
      concentrations (10 to 1,000 nM) of capsaicin. In the presence of extracellular
      Ca2+, a capsaicin-induced maximal release of SP obtained at 100 nM capsaicin was
      attenuated by either the phosphoinositide 3-kinase (PI3K) inhibitors (wortmannin
      and LY294002), the inositol 1,4,5-triphosphate (IP3)-induced Ca2+ release blocker
      (2-aminoethyl diphenylborinate, 2-APB) or a specific antagonist of TRPV1
      (capsazepine). In contrast, in the absence of extracellular Ca2+, only a high
      concentration (1 microM) of capsaicin induced a significant increase in the SP
      release, which was then completely abolished by either a mitogen-activated
      protein kinase kinase (MEK) inhibitor U0126 or capsazepine, and significantly
      inhibited by either thapsigargin (a Ca2+-ATPase inhibitor) or BAPTA-AM (a rapid
      Ca2+ chelator). In summary, the activation of TRPV1 by capsaicin modulates the SP
      release from DRG neurons via two different mechanisms, one requiring
      extracellular Ca2+, the activation of PI3K and the IP3-dependent intracellular
      Ca2+ release, and the other which is independent of extracellular Ca2+ but
      involves the activation of MEK. These data suggest that a distinct SP release
      mechanism exists on DRG through the activation of TRPV1 without extracellular
      Ca2+ by capsaicin to facilitate neuropeptide release.

PMID- 18034337
TI  - Fluorescent sensor array in a microfluidic chip.
AB  - Miniaturization and automation are highly important issues for the development of
      high-throughput processes. The area of micro total analysis systems (muTAS) is
      growing rapidly and the design of new schemes which are suitable for miniaturized
      analytical devices is of great importance. In this paper we report the
      immobilization of self-assembled monolayers (SAMs) with metal ion sensing
      properties, on the walls of glass microchannels. The parallel combinatorial
      synthesis of sensing SAMs in individually addressable microchannels towards the
      generation of optical sensor arrays and sensing chips has been developed.
      [figure: see text] The advantages of microfluidic devices, surface chemistry,
      parallel synthesis, and combinatorial approaches have been merged to integrate a
      fluorescent chemical sensor array in a microfluidic chip. Specifically, five
      different fluorescent self-assembled monolayers have been created on the internal
      walls of glass microchannels confined in a microfluidic chip.

PMID- 18034336
TI  - Selective PDE inhibitors rolipram and sildenafil improve object retrieval
      performance in adult cynomolgus macaques.
AB  - RATIONALE: Selective phosphodiesterase (PDE) inhibitors improve the formation of
      hippocampus-dependent memories in several rodent models of cognition. However,
      studies evaluating the effects of PDE inhibition on prefrontal cortex-dependent
      cognition and in monkeys are rare. OBJECTIVES: The present study investigates the
      effect of the PDE4 inhibitor rolipram and the PDE5 inhibitor sildenafil on object
      retrieval performance. Object retrieval is a prefrontal cortical-mediated task,
      which is likely to capture attention and response inhibition. MATERIALS AND
      METHODS: The ability to retrieve a food reward from a clear box with an open side
      positioned in various orientations was assessed in adult male cynomolgus monkeys
      (Macaca fascicularis). RESULTS: Rolipram (0.003-0.03 mg/kg, intramuscular [i.m.])
      and sildenafil (0.3-3 mg/kg, i.m.) dose-dependently increased correct first
      reaches during difficult trials, reaching significance at 0.01 and 1 mg/kg,
      respectively. For both drugs, correct reaches were increased approximately 20%;
      that is, performance was improved from approximately 50 to approximately 70%
      correct. CONCLUSIONS: Both rolipram and sildenafil improved object retrieval
      performance, thus demonstrating the cognition-enhancing effects of PDE inhibition
      on a prefrontal task of executive function in monkeys.

PMID- 18034338
TI  - Novel gel-based rapid test for non-instrumental detection of ochratoxin A in
      beer.
AB  - A rapid easy-to-use immunoassay was optimised for the non-instrumental detection
      of ochratoxin A (OTA) in beer. The analytical method involves preconcentration on
      the immunoaffinity layer inside a column followed by direct competitive ELISA
      detection in the same layer. The visual cut-off value, i.e. the lowest OTA
      concentration resulting in no colour development, was 0.2 microg L(-1). Assay
      validation was performed using samples spiked with OTA. Thirty-seven naturally
      contaminated samples were screened with the gel-based method developed and no
      false-negative results were obtained. The method described offers a simple, rapid
      and cost-effective screening tool, thus contributing to better health protection
      of consumers.

PMID- 18034339
TI  - Immediate CT findings following embolization of cerebral aneurysms: suggestion of
      blood-brain barrier or vascular permeability change.
AB  - INTRODUCTION: Although endovascular techniques are widely used for the treatment
      of cerebral aneurysms, the immediate postprocedural brain CT findings have not
      been reported. Therefore, in the present study we assessed the immediate
      postprocedural brain CT findings following the uneventful coil embolization of
      cerebral aneurysms. METHODS: Included in the study were 59 patients with 61
      cerebral aneurysms after uncomplicated coil embolization. Acute subarachnoid
      hemorrhage was present with 32 of the 61 aneurysms. All patients underwent a
      brain CT scan just before and within 2 h after the endovascular treatment. If the
      postprocedural CT scan revealed any new findings, a follow-up CT scan and/or MRI
      were performed within 24 h. The variables related to the abnormal CT findings
      were also evaluated. RESULTS: Among the 61 immediate brain CT scans, 26 (43%)
      showed abnormal findings, including cortical contrast enhancement (n=21, 34%),
      subarachnoid contrast enhancement (n=8, 13%), intraventricular contrast
      enhancement (n=5, 8%), and striatal contrast enhancement (n=2, 3%). Single or
      mixed CT findings were also seen. None of the 61 aneurysms was associated with
      new neurological symptoms after endovascular treatment, and all patients made an
      uneventful recovery. Abnormal findings were more likely to be found with lower
      body weight and with increased corrected amounts of contrast material and heparin
      (P<0.05). CONCLUSION: After uneventful endovascular treatment of cerebral
      aneurysms, the immediate brain CT findings can reveal various patterns of
      abnormal contrast enhancement. Recognizing the immediate brain CT findings is
      important, as they can mimic various diseases.

PMID- 18034340
TI  - Transfer of megaplasmid pKB1 from the rubber-degrading bacterium Gordonia
      westfalica strain Kb1 to related bacteria and its modification.
AB  - Because engineering of the 101.016-bp megaplasmid pKB1 of Gordonia westfalica Kb1
      failed due to the absence of an effective transfer system, pKB1 was transferred
      by conjugation from G. westfalica Kb1 to a kanamycin-resistant mutant of
      Rhodococcus opacus PD630 at a frequency of about 6.2 x 10(-8) events per
      recipient cell. Furthermore, pKB1 was transferred to G. polyisoprenivorans
      strains VH2 and Y2K and to Mycobacterium smegmatis by electroporation at
      frequencies of 5.5 x 10(3), 1.9 x 10(3), and 8.3 x 10(2) transformants per
      microgram plasmid DNA. The pKB1-encoded cadmium resistance gene cadA was used for
      selection in these experiments. Recombinant pKB1-containing G. polyisoprenivorans
      VH2 and M. smegmatis were then used to engineer pKB1. A kanamycin resistance
      cassette was inserted into the pKB1-encoded cadA gene, ligated to suicide plasmid
      pBBR1MCS-5, and the resulting plasmid was electroporated into plasmid-harboring
      strains. Homologous recombination between cadA on suicide plasmid and the
      respective sequence in pKB1 led to its integration into pKB1. Thus, two selection
      markers were accommodated in pKB1 to monitor plasmid transfer into Gordonia and
      related taxa for analysis of genes essential for rubber degradation and others.
      In this study, two transfer methods for large plasmids and strategies for
      engineering of pKB1 were successfully applied, thereby, extending the tool box
      for Gordonia.

PMID- 18034341
TI  - Imaging of sacral tumours.
AB  - All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves,
      notochord remnants, etc.) can give rise to benign or malignant tumours. Bone
      metastases and intraosseous sites of haematological malignancies, lymphoma and
      multiple myeloma are the most frequent aetiologies, while primary bone tumours
      and meningeal or nerve tumours are less common. Some histological types have a
      predilection for the sacrum, especially chordoma and giant cell tumour. Clinical
      signs are usually minor, and sacral tumours are often discovered in the context
      of nerve root or pelvic organ compression. The roles of conventional radiology,
      CT and MRI are described and compared with the histological features of the main
      tumours. The impact of imaging on treatment decisions and follow-up is also
      reviewed.

PMID- 18034342
TI  - Magnetic resonance imaging for osteoporosis.

PMID- 18034343
TI  - Monitoring ankylosing spondylitis therapy by dynamic contrast-enhanced and
      diffusion-weighted magnetic resonance imaging.
AB  - OBJECTIVE: The effects of different therapies on enthesitis/osteitis in active
      ankylosing spondylitis (AS) were evaluated by magnetic resonance imaging (MRI).
      The aim was to assess the role of quantitative MRI in the evaluation of AS
      treatment efficacy. MATERIALS AND METHODS: Thirty patients with active
      spondylitis or bilateral sacroiliitis were selected and followed up for 1 year.
      Ten of the patients were treated only with non-steroidal anti-inflammatory drugs,
      10 patients additionally received at baseline an intravenous pulse of
      glucocorticoids and 10 patients were treated with regular infusions of
      infliximab. Disease activity was measured according to clinical instruments and
      laboratory tests. For each patient, one selected inflamed lesion was followed
      from baseline through control visits quantitatively by diffusion-weighted imaging
      (DWI) measuring the apparent diffusion coefficient (ADC) and by dynamic contrast
      enhanced imaging (DCEI) with evaluation of the enhancement factor (f(enh)) and
      enhancement gradient (g(enh)). RESULTS: Clinical and quantitative MRI parameters
      diminished significantly with regression of the inflammatory activity. The
      improvement in AS was most pronounced in patients treated with infliximab; after
      12 months the ADC diminished from an average of 1.31 to 0.88 x 10(-3) mm(2)/s,
      f(enh) from 1.85 to 0.60, and g(enh) from 3.09 to 1.40 %/s. CONCLUSION: Diffusion
      weighted imaging and DCEI were shown to be effective in quantifying changes in
      inflammation in skeletal lesions during the treatment of AS, and could therefore
      be convenient for assessing treatment efficacy. To the best of our knowledge this
      is the first time DWI was used to evaluate the activity of skeletal inflammation
      in rheumatic diseases such as AS.

PMID- 18034344
TI  - Biological properties of 4-methyl-2,7-diamino-5,10-diphenyl-4,9-diazapyrenium
      hydrogensulfate (ADAP).
AB  - OBJECTIVE: 4-Methyl-2,7-diamino-5,10-diphenyl-4,9-diazapyrenium hydrogensulfate
      (ADAP) is a potential antitumor compound because of its DNA and RNA intercalating
      ability. In this study, cellular uptake, intracellular distribution as well as
      mechanism of action, antitumor activity in vitro and toxicity in vivo of ADAP
      were investigated. METHODS: Based on the fluorescence properties of ADAP, its
      entry and distribution into live cells were analyzed by fluorescence microscopy.
      The in vitro antiproliferative activity was determined using MTT test. For
      screening of topoisomerase II-targeted effects of ADAP, the cell-free assay and
      immunoband depletion assay were used. Expression of the genes c-mos, c-N-ras, c
      Ki-ras, c-H-ras, p53 and caspase 3 in Caco-2 cells treated with ADAP was examined
      by RT-PCR. Toxicity in vivo was determined using C3HHf/Bu Zgr/Hr mice treated by
      single or multiple doses of ADAP at a concentration of 25 mg/kg. RESULTS: ADAP in
      microM concentrations entered into MIAPaCa-2 cell's cytoplasm in 5 min and into
      nuclei in 60 min after administration. Intracellular distribution of ADAP
      depended on the period of treatment time. ADAP (0.1-100 microM) strongly
      inhibited the growth of both mouse (FsaR, SCCVII) and human tumor cells (HeLa,
      Caco-2, HT-29, MIAPaCa-2, HBL, HEp-2, SW620, MCF-7) compared to its weak
      cytotoxicity on controls and normal cells (WI38). Results of both topoisomerase
      II assays showed that ADAP is not a topoisomerase II poison. Expression of
      investigated genes was dependent on the incubation time, except for p53 and c-H
      ras. Morphological changes in tissues and organs of mice were not observed.
      Results of patohistological analysis have been confirmed by hematological and
      clinical-chemical analysis of blood of treated and non-treated animals.
      CONCLUSION: ADAP is a strongly bioactive compound with antitumor potential in
      vitro. The antitumor potential in vivo remains to be identified.

PMID- 18034345
TI  - Effect of pure curcumin, demethoxycurcumin, and bisdemethoxycurcumin on WT1 gene
      expression in leukemic cell lines.
AB  - PURPOSE: Leukemias are groups of hematological malignancies with high incidence
      and mortality rates in patients worldwide. There have been shown in many studies
      that Wilms' tumor1 (WT1) gene were highly expressed in leukemic blast cells.
      Curcuminoids, major active components of the spice turmeric, are well known for
      its anticancer. Curcuminoids consist of pure curcumin, demethoxycurcumin, and
      bisdemethoxycurcumin. In this study, the effect of each curcuminoids'components
      on WT1 gene expression in leukemic cell lines (K562, HL60, U937, and Molt4) was
      investigated. METHODS: The levels of WT1 mRNA and WT1 protein in leukemic cell
      lines were assessed by RT-PCR and Western blot analysis, respectively. RESULTS:
      It was found that the WT1 mRNAs were detected in all 4 types of leukemic cell
      lines. However, the WT1 protein levels were found only in the cell lines K562 and
      Molt4. Pure curcumin exhibited a strong inhibitory effect on WT1 mRNA and WT1
      protein expression. The treatment of leukemic cell lines with non-cytotoxic doses
      (5, 10, and 15 microM) of pure curcumin for 2 days reduced the level of WT1 mRNA
      expression and WT1 protein in a dose-dependent manner. In addition, pure curcumin
      at 10 microM significantly decreased the level of WT1 mRNA and protein in a time
      dependent manner. CONCLUSION: Pure curcumin, an excellent curcuminoid derivative,
      decreased WT1 gene expression in both transcriptional and translational levels.
      Thus, pure curcumin is one of a potential chemotherapeutic agent used for
      treatment of human leukemia. However, its chemotherapeutic property will need to
      be studied more in future.

PMID- 18034346
TI  - Automated neuropsychiatric measurements of information processing in
      fibromyalgia.
AB  - Aberrant central neurological functioning is believed to contribute to the
      abnormal sensations of fibromyalgia (FM). Most patients with FM complain of
      diminished cognitive function. This study sought to compare objective cognitive
      function between FM and healthy controls at baseline and to determine if
      symptomatic improvement was related to objective cognitive improvement. Automated
      neuropsychological assessment metrics (ANAM) was used to quantify neurocognitive
      function. Performance on ANAM was compared between subjects with FM,
      musculoskeletal pain, and pain-free controls. Ten separate FM subjects completed
      an 8-week comprehensive treatment program. Serial testing with ANAM and the
      Fibromyalgia Impact Questionnaire was conducted. Statistical analysis was
      performed using repeated Wilcoxon signed rank tests. No differences were noted on
      ANAM between controls and subjects with pain disorders. A clinical improvement
      (FIQ median change 33.9, P = 0.002) was noted with treatment without concomitant
      change in ANAM scores. No cognitive impairment in FM was demonstrated using ANAM.

PMID- 18034347
TI  - Cardiac T2* and lipid measurement at 3.0 T-initial experience.
AB  - This study was designed to assess whether breath-hold cardiac multiecho imaging
      at 3.0 T is achievable without significant image artefacts and if fat/water phase
      interference modulates the exponential T2* signal decay. Twelve healthy
      volunteers (mean age 39) were imaged on a Philips Intera 3.0 T MRI scanner.
      Multiecho imaging was performed with a breath-hold spoiled gradient echo sequence
      with a seven echo readout (echo times 1.15-8.05 ms, repetition time 11 ms) using
      a black-blood prepulse and volume shimming. T2* values were calculated with both
      mono- and biexpoential fits from the mean signal intensity of the
      interventricular septum. The global mean T2* was 27.3 ms +/- 6.4. The mean signal
      to-noise ratio (SNR) of the septum was 22.8 +/- 9.9, and the contrast-to-noise
      ratio (CNR) of the septum to the left ventricular cavity 20.3 +/- 9.4. A better
      fit was obtained with a biexponential model and the mean fat fraction derived was
      3.7%. Cardiac functional parameters were in the normal range and showed no
      correlation with T2*. Cardiac T2* estimation with gradient multiecho imaging at
      3.0 T can be achieved with minimal artefact and modelling the signal decay with a
      biexponential function allows estimation of myocardial lipid content as well as
      T2* decay.

PMID- 18034348
TI  - Gross total excision of pediatric giant cystic craniopharyngioma with huge
      retroclival extension to the level of foramen magnum by anterior trans petrous
      approach: report of two cases and review of literature.
AB  - PURPOSE: Craniopharyngiomas with a large posterior fossa extension beyond the
      level of the foramen magnum are very rare and usually removed in two stages. The
      objective of this paper is to report that such rare cases of giant cystic
      predominantly retrochiasmatic retroclival craniopharyngiomas can be completely
      excised by an anterior transpetrous approach in a single stage. MATERIALS AND
      METHODS: The first case was a 6-year-old boy who presented with a 1-year history
      of recurrent episodes of seizures, headache, and vomiting. The second case was a
      10-year-old girl who presented with history of headache, visual deterioration,
      and left-side hemiparesis for one and half years. Preoperative computed
      tomography (CT) and magnetic resonance imaging (MRI) in both these patients
      revealed a giant sellar suprasellar cystic lesion with areas of calcification and
      the lesion was predominantly retrochiasmatic with a huge retroclival posterior
      fossa extension down to the level of the C1 vertebra and laterally to the
      cerebellopontine angle. Gross total excision of both suprasellar and posterior
      fossa extensions could be done in both the patients through an anterior
      transpetrous transtentorial approach (Kawase's approach). RESULTS: Postoperative
      imaging (MRI/CT) revealed no obvious evidence of residual tumor. The first
      patient had right hemiparesis from which he recovered completely. The second
      patient died suddenly on postoperative day 4 after initial uneventful
      postoperative period, and the exact cause of death is not known. CONCLUSION:
      Giant cystic craniopharyngiomas, which are predominantly retrochiasmatic and
      associated with huge retroclival posterior fossa extensions, can be removed in
      single stage by Kawase's approach.

PMID- 18034349
TI  - TDP-43 immunoreactivity in neurodegenerative disorders: disease versus mechanism
      specificity.

PMID- 18034350
TI  - The effects of COX-1 and COX-2 inhibitors on prostaglandin synthesis and the
      formation of heterotopic bone in a rat model.
AB  - INTRODUCTION: Traumatic heterotopic ossification (HO) is a common clinical
      condition associated with various orthopedic procedures that involve injury to
      soft tissues near bone. In this study, we tested the hypothesis that the
      prophylactic effects of NSAID's in the treatment of HO are mediated via
      inhibition of the COX-2 enzyme. Here we describe a rat model that simulates HO in
      the human that was used to test the above hypothesis. MATERIALS AND METHODS:
      Heterotopic ossification was surgically induced in the quadriceps by injury to
      the muscle and femoral periosteum and transplantation of donor bone marrow cells
      containing osteoprogenitors into the site of injury. HO was imaged and quantified
      by micro-CT scanning of femurs removed from sacrificed animals at 6 weeks post
      injury, three-dimensional computer reconstructions of the scanned bones and
      computer-assisted morphometric analysis. Prostaglandin E(2) (PGE(2)) synthesis
      was quantified using an enzyme immunoassay system. The effects of a nonselective
      COX inhibitor or specific inhibitors of COX-1 or COX-2 following oral
      administration on the content of ectopic bone and PGE(2) were also measured.
      RESULTS: Micro-CT and histological analyses demonstrated that all of the femurs
      in operated limbs developed HO in the vastus lateralis muscle belly of the
      quadriceps close to the anterior femur. Only the COX-1,2 nonselective and COX-2
      inhibitors significantly decreased HO formation (by about one-third in each case;
      P < 0.05). PGE(2) synthesis at the site of injury was increased 50- and 100-fold
      (to 25 ng/g tissue) within 1 and 7 days, respectively, post-injury with the
      levels declining to near baseline within 2 weeks of surgery. Both the COX-1,2
      nonselective and COX-2 inhibitors significantly decreased PGE(2) levels to 25% of
      control HO levels within 24 h of the first administration, even at low dosages.
      The COX-1 inhibitor only produced the same effect after 1 week of administration.
      CONCLUSION: These findings suggest that although inhibitors of COX-2 or COX-1
      reduced PGE(2) synthesis, only the COX-2 enzyme plays a role in the mechanism of
      traumatic HO.

PMID- 18034351
TI  - Prevalence of high-grade squamous intraepithelial neoplasia (HiSIL) in
      symptomatic women referred to the colposcopy clinic with negative cytology.
AB  - OBJECTIVE: We have evaluated patients who were referred to the colposcopy clinic
      with postcoital and/or intermenstrual bleeding and suspicious looking cervix with
      normal smear tests (negative cytology) mainly to establish the incidence of
      underlying high-grade squamous intraepithelial neoplasia in these groups and also
      to look at our intervention rate. DESIGN: Retrospective study. SETTING:
      Colposcopy clinic in a District General Hospital in the United Kingdom.
      POPULATION: A total of 134 patients out of 812 new referrals to our colposcopy
      clinic during the study period were due to clinical indications only. RESULTS:
      Main indication for referral with negative cytology was post coital bleeding
      (47.8%). The main causes of postcoital and intermenstrual bleeding were cervical
      ectropions and polyps. The incidence high-grade squamous intraepithelial
      neoplasia (HiSIL) was 2.2% out of all the patients, which was determined after 66
      biopsies. CONCLUSION: In the majority of cases the pathology is benign. However
      the underlying prevalence of high-grade cervical disease in symptomatic women
      with normal smears necessitates colposcopy in selected cases. Prior assessment in
      the gynaecology clinic, to rule out common pathology like polyps and ectropions
      would reduce patient anxiety and inappropriate referrals to the clinic.

PMID- 18034352
TI  - Sarcomatoid carcinoma of the cervix: case report of a rare entity.
AB  - BACKGROUND: Sarcomatoid carcinoma of the cervix is a rare entity. To date, less
      than 20 cases have been reported in the English literature. CASE: We present a
      case of a 75-year-old multigravida woman who was treated with radiation therapy.
      CONCLUSION: It is an aggressive tumour and primary treatment with radiation in
      early stage disease offers an effective form of therapy.

PMID- 18034353
TI  - Treating common ear problems in pregnancy: what is safe?
AB  - In everyday practise, more than 80% of pregnant women receive one at least
      medication, often for ENT causes. The aim of the present paper is to review the
      literature on safety and administration of medical treatment for ear diseases, in
      pregnant women. The literature review includes Medline and database sources.
      Electronic links, related books and written guidelines were also included. The
      study selection was as follows: controlled clinical trials, prospective trials,
      case-control studies, laboratory studies, clinical reviews, systematic reviews,
      metanalyses, and case reports. The following drugs are considered relatively
      safe: beta-lactam antibiotics (with dose adjustment), macrolides (although the
      use of erythromycin and clarithromycin carries a certain risk), and acyclovir.
      Non-selective NSAIDs (until the 32nd week), nasal decongestants (with caution and
      up to 7 days), intranasal corticosteroids, with budesonide as the treatment of
      choice, first generation antihistamines, or cetirizine (third trimester) and
      loratadine (second and third trimester) from the second generation, H2 receptor
      antagonists (except nizatidine) and proton pump inhibitors (except omeprazole),
      can be used to relieve patients from the related symptoms. Meclizine and
      dimenhydrinate, as antiemetics in vertigo attacks; metoclopramide, vitamin B6 and
      ginger rhizome, alternatively. Low-dose diazepam and diuretics in severe cases of
      Meniere's disease (with caution). Systemic administration of prednisone and
      prednisolone can be considered in selected cases. By contrast, selective COX-2
      inhibitors, betahistine and vasodilating agents are contraindicated in pregnancy.
      Since otologic and neurotologic manifestations during pregnancy tend to seriously
      affect the quality of life of the expectant mothers, ENT surgeons should
      familiarise themselves with the basic guidelines and safety precautions for any
      related medication, in order to provide appropriate treatment.

PMID- 18034354
TI  - Saccades during symmetrical vergence.
AB  - BACKGROUND: When the eyes verge symmetrically along the median plane from far to
      near (convergence) or near to far (divergence), small saccades often occur. The
      current study aimed to: (i) characterize saccades during symmetrical vergence,
      (ii) describe the chronometry of saccade relative to that of vergence, and (iii)
      determine whether saccades mediate prefrontal control of vergence. METHODS: In
      Experiment 1, we recorded horizontal saccades during vergence in ten normals
      using an infrared tracker. Transcranial magnetic stimulation (TMS) was delivered
      over dorsolateral prefrontal cortex to assess its contribution in saccade
      production. In Experiment 2, saccades during vergence were recorded in horizontal
      and vertical planes in two other normals using a video-based tracker. RESULTS:
      Horizontal saccades, either pure or oblique (Exp.1), occurred in 84.0% of trials,
      58 ms after vergence onset, and averaged 1.5 degrees in amplitude. An
      idiosyncratic directional bias to the right was found for the rate and the
      latency of saccades. Prefrontal TMS had no influence on any saccade parameter.
      Pure horizontal, pure vertical and oblique saccades (Exp.2) occurred,
      respectively, in 60.4%, 72.4% and 25.4% of trials, 168 ms, 121 ms and 146 ms
      after vergence onset, averaging 1.1 degrees , 1.2 degrees and 1.5 degrees in
      amplitude. CONCLUSIONS: Chronometry of saccades during vergence suggests that
      they do not participate to vergence triggering, and that prefrontal control of
      vergence previously reported was not mediated by saccades.

PMID- 18034355
TI  - Intracellular aquaporins: clues for intracellular water transport?
AB  - Aquaporins (AQPs) are usually present at the plasma membrane to regulate influx
      and outflow of water and small molecules. They are important for the regulation
      of water homeostasis for the cells and organisms. AQPs are also present inside
      the cell, at the membranes of intracellular organelles. The roles of such AQPs
      have not yet been established. They will be clues to clarify the mechanisms of
      water and small solutes movements inside the cell. Recently, a new AQP subfamily
      has been identified with highly deviated asparagine-proline-alanine boxes,
      signature sequences for AQP. With limited homology less than 20%, this subfamily
      will be a superfamily of AQPs. Accordingly, it was tentatively named
      "superaquaporin subfamily," which is so far only present in multicellular
      organisms including plants, insects, nematodes, and vertebrates. Some
      superaquaporins are functionally water channels and localized intracellularly.
      AQP11, one of the two superaquaporins in mammals, has been shown to be important
      for the development of the proximal tubule as its disruption produced neonatally
      fatal polycystic kidneys in mice. Hence, recent identification of intracellular
      AQPs will open new areas of research on cell biology and expand the scope of
      AQPs.

PMID- 18034356
TI  - Expression of NO scavenging hemoglobin is involved in the timing of bolting in
      Arabidopsis thaliana.
AB  - Plants contain three classes of hemoglobin genes of which two, class 1 and class
      2, have a structure similar to classical vertebrate globins. We investigated the
      effect of silencing the class 1 non-symbiotic hemoglobin gene, GLB1, and the
      effect of overexpression of GLB1 or the class 2 non-symbiotic hemoglobin gene,
      GLB2, in Arabidopsis thaliana. Lines with GLB1 silencing had a significant delay
      of bolting and after bolting, shoots reverted to the rosette vegetative phase by
      formation of aerial rosettes at lateral meristems. Lines with overexpression of
      GLB1 or GLB2 bolted earlier than wild type plants. By germinating the lines in a
      medium containing the nitric oxide (NO) donor, sodium nitroprusside (SNP), it was
      demonstrated that both GLB1 and GLB2 promote bolting by antagonizing the effect
      of NO, suggesting that non-symbiotic plant hemoglobin controls bolting by
      scavenging the floral transition signal molecule, NO. So far, NO scavenging has
      only been demonstrated for class 1 non-symbiotic hemoglobins. A direct assay in
      Arabidopsis leaf cells shows that GLB1 as well as the class 2 non-symbiotic
      hemoglobin, GLB2, scavenge NO in vivo. NO has also been demonstrated to be a
      growth stimulating signal with an optimum at low concentrations. It was observed
      that overexpression of either GLB1 or GLB2 shifts the optimum for NO growth
      stimulation to a higher concentration. In conclusion, we have found that
      expression of NO scavenging plant hemoglobin is involved in the control of
      bolting in Arabidopsis.

PMID- 18034357
TI  - Pertussis and respiratory syncytial virus infections.
AB  - During the winter 2005-2006, all infants <4 months of age admitted for
      bronchiolitis or acute respiratory tract infection in a tertiary care pediatric
      hospital in Paris were tested for respiratory syncytial virus (RSV) and pertussis
      with real-time polymerase-chain reaction (RT-PCR). A positive pertussis-PCR was
      found in 14/90 (16%) infants infected with RSV and in 5/30 negative for RSV.
      Similar clinical symptoms were found in all RSV-positive infants with or without
      pertussis co-infection. Most infants (73%) were not vaccinated against pertussis,
      and the other children had received one or two injections. In conclusion,
      pertussis-RSV co-infection is common in young infants, and pertussis-PCR should
      be used, whenever available.

PMID- 18034358
TI  - Analysis of microbial community during biofilm development in an anaerobic
      wastewater treatment reactor.
AB  - The formation, structure, and biodiversity of a multispecies anaerobic biofilm
      inside an Upflow Anaerobic Sludge Bed (UASB) reactor fed with brewery wastewater
      was examined using complementary microbial ecology methods such us fluorescence
      in situ hybridization (FISH), denaturing gradient gel electrophoresis (DGGE), and
      cloning. The biofilm development can be roughly divided into three stages: an
      initial attachment phase (0-36 h) characterized by random adhesion of the cells
      to the surface; a consolidation phase (from 36 h to 2 weeks) defined by the
      appearance of microcolonies; and maturation phase (from 2 weeks to 2 months).
      During the consolidation period, proteobacteria with broad metabolic
      capabilities, mainly represented by members of alpha-Proteobacteria class
      (Oleomonas, Azospirillum), predominated. Beta-, gamma-, delta- (both
      syntrophobacteria and sulfate-reducing bacteria) and epsilon- (Arcobacter sp.)
      Proteobacteria were also noticeable. Archaea first appeared during the
      consolidation period. A Methanospirillum-like methanogen was detected after 36 h,
      and this was followed by the detection of Methanosarcina, after 4 days of biofilm
      development. The mature biofilm displayed a hill and valley topography with cells
      embedded in a matrix of exopolymers where the spatial distribution of the
      microorganisms became well-established. Compared to the earlier phases, the
      biodiversity had greatly increased. Although alpha-Proteobacteria remained as
      predominant, members of the phyla Firmicutes, Bacteroidete, and Thermotogae were
      also detected. Within the domain Archaea, the acetoclastic methanogen
      Methanosaeta concilii become dominant. This study provides insights on the
      trophic web and the shifts in population during biofilm development in an UASB
      reactor.

PMID- 18034359
TI  - Clinicopathologic characteristics and malignant potential of colorectal flat
      neoplasia compared with that of polypoid neoplasia.
AB  - PURPOSE: Because of their potential for malignancy, flat colorectal neoplasias
      are a current topic of debate. This study was designed to investigate the
      clinicopathologic features of flat neoplasia and to compare them with those of
      polypoid neoplasia, as well as to identify the determinants of malignant
      transformation of both flat and polypoid colorectal neoplasia. METHODS: A
      prospective, cross-sectional study of 3,360 patients diagnosed with adenomas via
      total colonoscopy and polypectomy was performed at 11 tertiary medical centers
      between July 2003 and July 2004. In this study, potential risk factors for
      malignant transformation were analyzed. If multiple adenomas were identified,
      then only the adenoma with the most advanced degree of histology was recorded for
      the patient. RESULTS: Of a total of 3,360 neoplasias identified, we found that
      the incidence of flat and polypoid neoplasias were 207 (6.2 percent) and 3,153
      (93.8 percent), respectively. Patients with flat neoplasias tended to be older
      (59.6 vs. 57.1, P < 0.01), with the neoplasia located more frequently in the
      right colon than polypoid neoplasias (49.3 percent vs. 32 percent, P < 0.01). The
      incidence of high-grade dysplasia or cancer in flat neoplasias was similar to
      that of polypoid neoplasias (5.4 percent vs. 4.6 percent, P = 0.36). Multivariate
      analysis revealed that a size of > or =11 mm (odds ratio, 6.8; 95 percent
      confidence interval, 4.8-9.7) and location in the left colon (odds ratio, 1.6; 95
      percent confidence interval, 1.1-2.4) were significant determinants for the
      malignancy potential of colonic neoplasias. CONCLUSIONS: The clinicopathologic
      indices for the propensity of malignant transformation in colorectal neoplasias
      were a size > or =11 mm and location in the left colon rather than flat gross
      morphology.

PMID- 18034360
TI  - Feasibility study of degradation of phenol in a fluidized bed bioreactor with a
      cyclodextrin polymer as biofilm carrier.
AB  - This work is focused on the evaluation of a beta-cyclodextrin polymer as a
      carrier medium in a fluidized bed bioreactor treating aqueous phenol as a model
      pollutant. The insoluble polymer support was obtained in the shape of spherical
      beads by crosslinking beta-cyclodextrin with epichlorohydrin. A batch of swollen
      polymer particles was loaded into the reactor and inoculated with a mixed
      bacterial culture. Bacterial growth on the polymer beads was initially stimulated
      by glucose addition to the medium, and then gradually replaced with phenol. The
      operational variables studied after the acclimation period included phenol load,
      hydraulic residence time and recirculation flow rate. Low hydraulic residence
      times and moderate phenol loads were applied. The elimination capacity was
      usually about 1.0 kg-phenol/m(3)d, although a maximum of 2.8 kg-phenol/m(3)d was
      achieved with a retention time of only 0.55 h. The depuration efficiency was not
      affected by the recirculation flow rate in the range studied. Neither operational
      nor support stability problems were detected during the operation. A high degree
      of expansion was achieved in the bioreactor due to the hydrogel nature of the
      cyclodextrin polymer and, consequently, a low energy requirement was necessary to
      fluidize the bed.

PMID- 18034361
TI  - Assessment of heavy metals in two commercial fish species of four Turkish seas.
AB  - There is an increasingly need to assess the contaminant levels in fish as
      indicators of the health and well-being of both the fish and their consumers,
      including humans. Fish samples were collected through the coastal waters of
      Turkey and the contents of cadmium, copper, chrome, copper, iron, manganese,
      nickel, zinc and lead in the liver and muscle tissues were determined by ICP-AES.
      The highest levels of each metal were found in the liver and this was followed by
      the muscle in both species. Among the metals analyzed, Cu, Zn and Fe were the
      most abundant in the different tissues while Cd and Pb were the least abundant
      both in Mullus barbatus (red mullet) and Merlangius merlangus (whiting). Regional
      changes in metal (Cd, Cu, Pb, Fe and Zn) concentration were observed in the
      tissues of both species, but these variations may not influence consumption
      advisories.

PMID- 18034362
TI  - Optimal extension of the rain gauge monitoring network of the Apulian Regional
      Consortium for Crop Protection.
AB  - The goal of this paper is to provide a methodology for assessing the optimal
      localization of new monitoring stations within an existing rain gauge monitoring
      network. The methodology presented, which uses geostatistics and probabilistic
      techniques (simulated annealing) combined with GIS instruments, could be
      extremely useful in any area where an extension of whatever existing
      environmental monitoring network is planned. The methodology has been applied to
      the design of an extension to a rainfall monitoring network in the Apulia region
      (South Italy). The considered monitoring network is managed by the Apulian
      Regional Consortium for Crop Protection (ARCCP), and, currently consists of 45
      gauging stations distributed over the regional territory, mainly located on the
      basis of administrative needs. Fifty new stations have been added to the existing
      monitoring network, split in two groups: 15 fixed and 35 mobile stations. Two
      different methods were applied and tested: the Minimization of the Mean of
      Shortest Distances method (MMSD) and Ordinary Kriging (OK) whose related
      objective function is estimation variance. The MMSD, being a purely geometric
      method, produced a spatially uniform configuration of the gauging stations. On
      the contrary, the approach based on the minimization of the average of the
      kriging estimation variances, produced a less regular configuration, though a
      more reliable one from a spatial standpoint. Nevertheless, the MMSD approach was
      chosen, since the ARCCP's intention was to create a new monitoring network
      characterized by uniform spatial distribution throughout the regional territory.
      This was the most important constraint given to the project by the ARCCP, whose
      main objective was to accomplish a territorial network capable of detecting
      hazardous events quickly. A seasonal aggregation of the available rainfall data
      was considered. The choice of the temporal aggregation in quarterly averages
      allowed four different optimal configurations to be determined per season. The
      overlapping of the four configurations allowed a number of new station locations,
      which tended to remain fixed season after season, to be identified. Other
      stations, instead, changed their coordinates considerably over the four seasons.
      Constraints were defined in order to avoid placing new monitoring locations
      either near existing stations, belonging to other Agencies, or near the coast
      line.

PMID- 18034363
TI  - Environmental impact of coal washery and Damodar River water on the morphometry
      and biochemical changes of maize (Zea mays L.) and soil health.
AB  - Enormous quantity of water is used for coal beneficiation and accordingly huge
      amount of effluents are being generated. In this study an attempt was made to
      evaluate the potential of this effluent water for irrigation. Water samples were
      collected from three different points (a) feeding point, (b) thickening point,
      and (c) outlet point of coal washery, and from Damodar River for monitoring the
      water quality. The samples were analyzed for various parameters and compared with
      prescribed standard, which revealed that the total suspended solids of thickening
      point and Damodar River were higher. A pot experiment with maize was conducted to
      study the suitability of this coal washery water for irrigation. Pots were
      irrigated with water from the three points of washery and Damodar River in two
      concentrations (100% and 50% dilution with distilled water); pure distilled water
      was used for control. There was 100% germination in all the treatments. The plant
      growth, chlorophyll content and soil quality parameters were significantly better
      in washery and Damodar River water treated pots. The Damodar River water and
      washery water from feeding and outlet point could be successfully used for
      irrigation. In general mixing with good quality water has shown better results.

PMID- 18034364
TI  - Reflection and reflective practice in health professions education: a systematic
      review.
AB  - The importance of reflection and reflective practice are frequently noted in the
      literature; indeed, reflective capacity is regarded by many as an essential
      characteristic for professional competence. Educators assert that the emergence
      of reflective practice is part of a change that acknowledges the need for
      students to act and to think professionally as an integral part of learning
      throughout their courses of study, integrating theory and practice from the
      outset. Activities to promote reflection are now being incorporated into
      undergraduate, postgraduate and continuing medical education, and across a
      variety of health professions. The evidence to support and inform these
      curricular interventions and innovations remains largely theoretical. Further,
      the literature is dispersed across several fields, and it is unclear which
      approaches may have efficacy or impact. We, therefore, designed a literature
      review to evaluate the existing evidence about reflection and reflective practice
      and their utility in health professional education. Our aim was to understand the
      key variables influencing this educational process, identify gaps in the
      evidence, and to explore any implications for educational practice and research.

PMID- 18034365
TI  - Transcriptional activation of Cor/Lea genes and increase in abiotic stress
      tolerance through expression of a wheat DREB2 homolog in transgenic tobacco.
AB  - Wdreb2, previously isolated as a DREB2 homolog, is expressed in wheat seedlings
      under abiotic stresses, such as cold, drought, and high salinity, and following
      treatment with exogenous ABA. In the present study, we generated transgenic
      tobacco plants expressing Wdreb2 to clarify roles of Wdreb2 in stress tolerance
      and the direct trans-activation of Cor/Lea genes by WDREB2. Wdreb2 expression
      significantly improved freezing and osmotic stress tolerance in tobacco plants.
      Several putative stress- and ABA-responsive cis-elements were found in the 5'
      upstream regions of four wheat Cor/Lea genes, Wdhn13, Wrab17, Wrab18, and Wrab19.
      The expression level of a gusA reporter gene under control of Cor/Lea promoter
      sequences was enhanced by cold, drought and ABA treatment in transgenic tobacco
      plants. Moreover, the gusA expression level was markedly enhanced by Wdreb2
      expression under nonstressful conditions. These results clearly indicate that
      WDREB2 acts as a transcription factor and positively regulates Wdhn13, Wrab17,
      Wrab18, and Wrab19 in the development of multiple abiotic stress tolerance in
      wheat.

PMID- 18034366
TI  - Lack of replication of genetic associations with human longevity.
AB  - The exceptional longevity of centenarians is due in part to inherited genetic
      factors, as deduced from data that show that first degree relatives of
      centenarians live longer and have reduced overall mortality. In recent years, a
      number of groups have performed genetic association studies on long-living
      individuals (LLI) and young controls to identify alleles that are either
      positively or negatively selected in the centenarian population as consequence of
      a demographic pressure. Many of the reported studies have shown genetic loci
      associated with longevity. Of these, with the exception of APOE, none have been
      convincingly reproduced. We validated our populations by typing the APOE locus.
      In addition, we used 749 American Caucasian LLI, organized in two independent
      tiers and 355 American Caucasian controls in the attempt to replicate previously
      published findings. We tested Klotho (KL)-VS variant (rs952706), Cholesteryl
      Ester Transfer Protein (CETP) I405V (rs5882), Paraoxonase 1 (PON1) Q192R (rs662),
      Apolipoprotein C-III (APOC3) -641C/A (rs2542052), Microsomal Transfer Protein
      (MTP) -493G/T (rs2866164) and apolipoprotein E (APOE) epsilon2 and epsilon4
      isoforms, (rs7412 and rs429358) haplotypes respectively. Our results show that,
      at present, except for APOE, none of the selected genes show association with
      longevity if carefully tested in a large cohort of LLI and their controls,
      pointing to the need of larger populations for case-control studies in extreme
      longevity.

PMID- 18034367
TI  - Study of plasma induced chemistry by DC discharges in CO2/N2/H2O mixtures above a
      water surface.
AB  - The chemistry induced by atmospheric pressure DC discharges above a water surface
      in CO(2)/N(2)/H(2)O mixtures was investigated. The gaseous mixtures studied
      represent a model prebiotic atmosphere of the Earth. The most remarkable changes
      in the chemical composition of the treated gas were the decomposition of CO(2)
      and the production of CO. The concentration of CO increased logarithmically with
      the increasing input energy density and an increasing initial concentration of
      CO(2) in the gas. The highest achieved concentration of CO was 4.0 +/- 0.6 vol.
      %. The production of CO was crucial for the synthesis of organic species, since
      reactions of CO with some reactive species generated in the plasma, e. g. H* or
      N* radicals, were probably the starting point in this synthesis. The presence of
      organic species (including the tentative identification of some amino acids) was
      demonstrated by the analysis of solid and liquid samples by high-performance
      liquid chromatography, infrared absorption spectroscopy and proton-transfer
      reaction mass spectrometry. Formation of organic species in a completely
      inorganic CO(2)/N(2)/H(2)O atmosphere is a significant finding for the theory of
      the origins of life.

PMID- 18034368
TI  - Nutritional management of patients with urea cycle disorders.
AB  - The nutritional management of patients with urea cycle disorders (UCDs) involves
      restriction of dietary protein along with provision of adequate protein-free
      energy, essential amino acid supplements, and vitamins and minerals in
      combination with nitrogen-scavenging drugs. The present paper discusses nutrition
      therapy for a range of circumstances: during an acute hyperammonaemic episode and
      at hospital discharge; before, during, and after surgery; and for lifelong
      chronic management of UCDs.

PMID- 18034369
TI  - Asymptomatic dermatophyte scalp carriage: laboratory diagnosis, epidemiology and
      management.
AB  - Asymptomatic carrier is defined as an individual who has dermatophyte-positive
      scalp culture without signs or symptoms of tinea capitis. The prevalence of
      asymptomatic carriage differs from region to region with a rate of 0.1-49%.
      Anthropophilic dermatophytes, Trichophyton tonsurans and Trichophyton violaceum,
      have been generally associated with high rates of asymptomatic carriage. Hence,
      the presence of dermatophytes on healthy scalp hairs of children may be a
      potential source of infection for schoolmates, playmates and/or households.
      Although it was also reported in adults, most carriage has been observed in
      children especially among those between 4 and 8 years of age, while male to
      female ratios vary between studies. It is still unclear, whether carriers should
      be treated with topical antifungal shampoos or oral antifungals or both, as some
      studies indicate that some untreated cases become culture-negative after 2-12
      months. This review provides details on related dermatophyte fungi, laboratory
      diagnosis, epidemiology, ways of spreading as well as treatment and follow-up
      results of asymptomatic carriage. An integration into the school health programs
      is proposed, which will render the possible dealing of the subject in a
      comprehensive and reasonable manner.

PMID- 18034370
TI  - High-level expression of orange fluorescent protein in the silkworm larvae by the
      Bac-to-Bac system.
AB  - This novel orange fluorescent protein (OFP) emits brilliant orange fluorescent
      light. OFP has high fluorescence quantum yield, fast maturation rate, and
      stability, which imply this protein should be the most favorable biotechnological
      tools used to investigate the function of target gene by visualizing, monitoring,
      and quantifying in living cells. B. mori, silkworm has been used as an important
      bioreactor for the production of recombinant proteins through baculovirus
      expression system (BES). In this paper, we used infection technique which
      introduced the baculovirus DNA into silkworms using a cationic lipofectin reagent
      instead of directly injecting the virus, and demonstrated a high-level expression
      of the orange fluorescent protein (OFP) gene in the Bombyx mori, silkworm larvae.
      When recombinant rBacmid/BmNPV/OFP DNA ranging from 50-100 ng/larval was
      injected, a sufficient OFP expression in hemolymph was harvested. The recombinant
      viruses could be obtained from the hemolymph of infected larvae and stored as
      seed which could be used for the large-scale expression. This procedure omitted
      the costly and labor-consumed insect cell culture. Further investigation of OFP
      should provide us with more insight in unlocking the mystery of the mechanisms of
      autocatalytic bioluminescence and its utilization in biotechnology.

PMID- 18034371
TI  - Silkworm powder containing manganese superoxide dismutase regulated the immunity
      and inhibited the growth of Hepatoma 22 cell in mice.
AB  - The effects of SOD contained silkworm powder on immune regulation and inhibition
      against Hepatoma 22 tumor cells in vivo were investigated. The activity of
      natural killer cell (NK) and the ConA-stimulated spleen proliferation were
      measured. The results found that the SOD-contained silkworm powder caused an
      enhancement on NK cell activity, which implied this material modulated the immune
      system in mice in vivo. The NK cell activities of Hepatoma 22 tumor modeled mice
      treated with silkworm powder including SOD were increased significantly compared
      to a modeled control and silkworm powder without SOD, reaching 36.18%. In
      addition, the ConA-stimulated spleen proliferation of SOD treated mice was higher
      than that of the controls. The treatment of SOD contained silkworm powder
      presented 40.3% of average inhibition rate to Hepatoma 22 tumor, showing stronger
      inhibition against tumor. There were no significant difference in body weight
      between modeled control and SOD silkworm powder feeding in Hepatoma 22 tumor
      modeled mice, suggesting the SOD silkworm powder is safety as an inhabitant to
      tumor. In conclusion, these findings demonstrate that administration of silkworm
      powder containing SOD results in activation of NK cells and immunity, suggesting
      the silkworm powder containing SOD plays a positive role in tumor inhibition.

PMID- 18034372
TI  - Centrifugal forces within usually-used magnitude elicited a transitory and
      reversible change in proliferation and gene expression of osteoblastic cells UMR
      106.
AB  - Centrifugation is an important step in biochemical and molecular biological
      researches. But the effects of centrifugal stress on cells are still unclear. In
      this study, osteoblastic cells UMR-106 were subjected to a moderate centrifugal
      stress at 209 x g for 10 min. Then the cell proliferation and gene transcription
      after centrifugation were analyzed with flow cytometry and Real-time RT-PCR
      techniques, respectively. The result showed that the cell proliferation and mRNA
      expression of Runx2/Cbfa1, Collagen I and osteocalcin changed shortly after
      centrifugal loading, but recovered to pre-load levels within 24 h. A dose
      response study of exposure cells to centrifugal force at 209, 253 and 301 x g
      showed that the centrifugal forces within usually-used range can rapidly
      influenced the mRNA expression of the osteoblast-specific genes, but no
      statistical differences were found among the three centrifugal magnitudes. And
      the fast regulation in the investigated genes was proved to be related to
      increased c-fos mRNA levels and subsequent activation of RTK and integrity of
      cytoskeleton construction. The result showed that the osteoblastic cells
      displayed a fast auto-regulation to usually-used centrifugal stress through
      multiple signal pathways.

PMID- 18034373
TI  - Subjective quality of life in outpatients with schizophrenia in Hong Kong and
      Beijing: relationship to socio-demographic and clinical factors.
AB  - PURPOSE: This study compared the subjective quality of life (SQOL) in
      schizophrenia patients living with their families in Hong Kong (HK) and Beijing
      (BJ) and explored the relationship between SQOL and basic socio-demographic and
      clinical factors. MATERIALS AND METHODS: Two hundred and sixty-four clinically
      stable outpatients with schizophrenia were randomly selected in HK and 258
      counterparts matched according to age, sex, age at onset, and length of illness
      in BJ. SQOL and psychiatric status were assessed with standard rating
      instruments. RESULTS: There was no significant difference in any of SQOL domains
      between the two cohorts after controlling for potentially confounding variables.
      Positive, depressive and anxiety symptoms and drug-induced extrapyramidal side
      effects (EPS) were all significantly correlated with SQOL. Multiple regression
      analysis revealed that only depressive symptoms predicted all SQOL domains in
      both groups. Having removed depressive symptoms from the model, positive symptoms
      predicted all domains, anxiety predicted all but social domains, use of
      benzodiazepines (BZD) predicted all but physical domains, EPS predicted physical
      domain, and history of suicide predicted social domain in HK; anxiety predicted
      all domains, positive symptoms predicted all but physical domains, EPS, use of
      BZD and history of suicide all predicted physical domains, and length of illness
      predicted environmental domain in BJ. CONCLUSION: Despite considerable
      differences between the two sites in terms of health care delivery and the
      economic conditions of the subjects, SQOL did not differ between HK and BJ. The
      conclusion is in line with previous studies that suggested that patients' SQOL
      was independent of their living standard as long as it reached a certain minimum
      level. SQOL was more strongly related to the severity of depressive symptoms and
      had weak association with socio-demographic factors.

PMID- 18034375
TI  - Depot naltrexone use for opioid dependence in Australia: large-scale use of an
      unregistered medication in the absence of data on safety and efficacy.

PMID- 18034374
TI  - Functional protein expression from a DNA based wheat germ cell-free system.
AB  - Wheat germ based eukaryotic cell-free systems have been shown to be applicable
      for both functional and structural analyses of proteins. However, the existing
      methods might require specialized instrumentation and/or a separate mRNA
      synthesis step. We have developed a DNA based, highly productive, coupled
      transcription/translation wheat germ cell-free system that incorporates the
      normally separate mRNA synthesis step and does not require specialized
      instrumentation. Using a small-volume batch reaction with fluorescence labeling,
      DNA templates predicted to encode proteins could be quickly screened for their
      ability to direct the expression of proteins of the appropriate size. Protein
      yield can be increased as much as 2 to 4-fold in this system using a dialysis
      reaction, reaching approximately 200-440 microg/ml in 10-20 h. Furthermore,
      enzyme activities can be assayed directly in the extract without further
      purification. Simple purification with affinity tags can be achieved in one-step
      and with minor modifications, efficient SeMet and [U-15N] labeling of >95% can be
      accomplished in this system. Thus, this efficient cell-free expression system can
      facilitate both functional and structural proteomics.

PMID- 18034376
TI  - Newspaper coverage of drug policy: an analysis of pre-election reporting of the
      Greens' drug policy in Australia.
AB  - INTRODUCTION AND AIMS: With the headline 'Ecstasy Over The Counter' in a popular
      daily newspaper, the debate on drug policy officially entered the arena of the
      2003 New South Wales (Australia) State Election. The debate resurfaced in the
      lead-up to the 2004 Australian Federal Election. This paper analyses the pre
      election coverage of drug policy issues in four Australian newspapers. DESIGN AND
      METHODS: Four high-circulation daily newspapers were monitored for a one-month
      period prior to both elections and analysed for their coverage of drug policy,
      particularly with respect to the policy of the Greens. RESULTS: The newspapers
      took different perspectives on drug policy issues, with two framing it in emotive
      terms as a moral debate and two framing it as political manoeuvring. DISCUSSION
      AND CONCLUSION: The newspapers focused upon emotive and sensationalist factors.
      They did not provide their readers with information or a rationale for the
      formulation of drug policy, be this from a harm minimisation or zero tolerance
      perspective.

PMID- 18034377
TI  - Client satisfaction and risk behaviours of the users of syringe dispensing
      machines: a pilot study.
AB  - INTRODUCTION AND AIMS: The study examines risk behaviours of the users of syringe
      dispensing machines (SDMs) and evaluates the usefulness of these machines in
      providing injecting drug users (IDUs) with sterile injecting equipment. DESIGN
      AND METHODS: Self-administered questionnaires were used among users of SDMs in an
      Area Health Service of Sydney. RESULTS: The majority of the 167 participants
      reported being happy with the quality of the SDM services. Problems identified
      with machines were that they were often broken or jammed (32.8% respondents), not
      in the right place (21.9%) or require money (16.7%). Just over half (50.9%) of
      the IDUs use SDMs only from 5 p.m. to 9 a.m., the time when almost all other
      outlets for accessing sterile injecting equipment remain closed. Relatively young
      IDUs (age < or = 30 years) were more likely to prefer SDMs over staffed needle
      syringe programmes (NSPs) compared with older users (age > 30) and to identify
      stigma (a desire to hide their identity or not liking the way people treat them
      at staffed NSPs or chemists) as a main reason for using these machines. Primary
      users of SDMs do not differ from primary users of NSP/chemists in terms of
      sharing of needles. Those users who had shared in the last month were nearly four
      times as likely to have never used condoms in sexual encounters over that period
      (95% confidence interval: 1.2 - 14.5). DISCUSSION AND CONCLUSION: SDMs appear to
      complement other outlets of NSPs. Providing free-of-cost equipment from SDMs
      should be considered carefully, as needing money to buy equipment was a reason
      given for sharing of needles by 35% of those who shared.

PMID- 18034378
TI  - What does it mean to want to quit?
AB  - INTRODUCTION AND AIMS: To report on the prevalence of attitudes and beliefs about
      the importance of wanting to quit and need for use of cessation assistance, that
      may act as barriers to quitting smoking and adopting cessation assistance. DESIGN
      AND METHODS: National telephone survey of 802 randomly selected adults (685
      smokers, 117 recent quitters). RESULTS: Seventy per cent of smokers believed that
      'wanting to quit' was both a necessary and sufficient condition for being able to
      quit. While only one-third of smokers believed that they were too addicted to be
      able to quit, only a quarter believed they could quit any time they want to.
      Belief that use of cessation assistance is a sign of weakness was endorsed by 35%
      of participants, and related to stage of change. DISCUSSION AND CONCLUSIONS:
      Beliefs about the importance of wanting to quit are commonly held. Many smokers
      appear to believe that a rational, unambivalent desire to quit is needed before
      it is worthwhile trying. Short-term impulses to act are not perceived as
      sufficient. The role of cessation assistance in helping smokers form a rational
      desire to quit appears to be poorly understood by the majority of smokers. There
      is a need to engender greater understanding of the potential value of cessation
      aids to smokers experiencing ambivalence about wanting to quit.

PMID- 18034379
TI  - How effective is the revised regulatory code for alcohol advertising in
      Australia?
AB  - INTRODUCTION AND AIMS: Australia, like several other countries, has a self
      regulatory approach to advertising. However, in recent years the effectiveness of
      the regulatory system has been questioned, and there have been increasing public
      calls for an overhaul of the system. Following a formal review in 2003, the
      Ministerial Council on Drug Strategy proposed a revised Alcoholic Beverages
      Advertising Code (ABAC), which came into operation in 2004. DESIGN AND METHODS:
      The purpose of the present study was to examine the effectiveness of this revised
      system. From May 2004 until March 2005 television and magazine advertising
      campaigns were monitored for alcohol products. Over this period 14 complaints
      against alcohol advertisements were lodged with the self-regulatory board, and
      the authors recruited an independent expert panel to assess the advertisements
      and complaints. RESULTS: In eight of the 14 cases a majority of the judges
      perceived the advertisement to be in breach of the code, and in no cases did a
      majority perceive no breach. Conversely, however, none of the complaints were
      upheld by the Advertising Standards Board (ASB) and only one by the ABAC Panel.
      DISCUSSION AND CONCLUSIONS: The results of this study suggest that the decisions
      made by the ASB in relation to complaints against alcohol advertisements are not
      in harmony with the judgement of independent experts, and that the ASB may not be
      performing an adequate job of representing community standards or protecting the
      community from offensive or inappropriate advertisements. Further, it appears
      that the revisions to the ABAC code, and associated processes, have not reduced
      the problems associated with alcohol advertising in Australia.

PMID- 18034380
TI  - Barriers and missed opportunities to HIV testing among injection drug users in
      two Mexico--US border cities.
AB  - INTRODUCTION AND AIMS: Despite increasing HIV prevalence in cities along the
      Mexico--US border, HIV testing among high-risk populations remains low. We sought
      to identify barriers associated with HIV testing among injection drug users
      (IDUs) in Tijuana and Ciudad Juarez, the two largest Mexican border cities
      located across from San Diego, California and El Paso, Texas, respectively.
      DESIGN AND METHODS: In 2005, 222 IDUs in Tijuana and 205 IDUs in Ciudad Juarez
      were recruited by respondent-driven sampling and administered a questionnaire to
      collect socio-demographic, behavioural and HIV testing history data. Blood
      samples were provided for serological testing of HIV, hepatitis C virus (HCV) and
      syphilis. RESULTS: Only 38% and 30% of respondents in Tijuana and Ciudad Juarez,
      respectively, had ever had an HIV test. The factors independently associated with
      never having been tested for HIV differed between the two sites, except for lack
      of knowledge on HIV transmission, which was independently associated in both
      locales. Importantly, 65% of those who had never been tested for HIV in both
      cities experienced at least one missed opportunity for voluntary testing,
      including medical visits, drug treatment and spending time in jail. DISCUSSION
      AND CONCLUSIONS: Among this high-risk IDU population we found HIV testing to be
      low, with voluntary testing in public and private settings utilised inadequately.
      These findings underscore the need to expand voluntary HIV education and testing
      and to integrate it into services and locales frequented by IDUs in these Mexico-
      US border cities.

PMID- 18034381
TI  - Dispensing opioid substitution treatment: practices, attitudes and intentions of
      community-based pharmacists.
AB  - INTRODUCTION AND AIMS: Community-based pharmacists (CPs) play a pivotal role in
      the provision of opioid substitution treatment (OST). This study examined
      practices, experiences, attitudes and intentions of a sample of South Australian
      pharmacists involved with the provision of OST. DESIGN AND METHODS: A random
      sample, stratified by geographic location, of 50 SA CPs were administered a
      telephone survey. The survey included pharmacist and pharmacy details, current
      practices, problems experienced, attitudes towards and future intentions in
      relation to the provision of OST. RESULTS: Pharmacists indicated high levels of
      support for the OST programme and most (98%) intended to continue providing OST.
      Sixty-four per cent of all pharmacists, and significantly more rural pharmacists
      (90%), indicated that they were willing to take on additional clients.
      Metropolitan pharmacists dosed greater numbers of OST clients (median = 7) than
      rural pharmacists (median = 4). There was a strong positive correlation between
      number of regular clients seen and problems experienced by pharmacists. Seventy
      per cent of pharmacists reported detecting no diversion of pharmacotherapy
      medication. DISCUSSION AND CONCLUSIONS: Despite reports to the contrary,
      pharmacists appear to be generally positively predisposed to providing OST.
      Policies aimed at retaining pharmacists, particularly in resource poor rural
      areas, could consider embracing a shared-care approach between general
      practitioners and pharmacists.

PMID- 18034382
TI  - The influence of alcohol and tobacco use in orthopaedic inpatients on
      complications of surgery.
AB  - INTRODUCTION AND AIMS: Tobacco use and heavy alcohol consumption are associated
      with increased morbidity and mortality. There is limited research on the
      correlation between tobacco and risky levels of alcohol use and the possible
      complications associated with a hospital admission. The underestimation of
      problem drinking, in particular, has obvious repercussions for the management of
      patients in hospital. If alcohol-related problems go undetected or unrecorded,
      treatment may be inadequate or inappropriate. The aims of the project were to
      assess the prevalence of high-risk alcohol and tobacco use in orthopaedic in
      patients and to examine any relationship between alcohol and tobacco use and the
      number and type of complications, management and length of stay. DESIGN AND
      METHOD: One hundred and fifty-three consecutive orthopaedic admissions to the
      Orthopaedic Ward at Lismore Base Hospital were screened using the Drinkcheck
      questionnaire, which is based on the Alcohol Use Disorders Identification Test
      (AUDIT), but which also screens for tobacco use. Nursing staff on the ward
      completed a Complications Evaluation Questionnaire (CEQ). The risk status of the
      subjects was compared to the number and type of complications, to assess any
      effects of alcohol and tobacco on post-surgical complications. RESULTS:
      Significant correlations were found between tobacco use, hazardous and harmful
      alcohol use and numerous medical complications and behavioural problems.
      Behavioural problems associated with risky alcohol use included verbal abuse,
      agitation and sleep disturbances, particularly in men; problems associated with
      tobacco use included agitation and non-compliance. DISCUSSION AND CONCLUSIONS:
      Orthopaedic patients who smoke and/or drink heavily prior to surgery may have
      more non-medical complications than non-smokers and light or non-drinkers. All
      surgery patients should thus be screened for alcohol and tobacco use and alcohol
      withdrawal, which may cause other symptoms such as behavioural problems, non
      compliance and verbal abuse post-surgery.

PMID- 18034383
TI  - An outcome evaluation of the New South Wales Sober Driver Programme: a remedial
      programme for recidivist drink drivers.
AB  - INTRODUCTION AND AIMS: Recidivist drink drivers pose a considerable threat to
      public safety. The present study evaluates the effectiveness of a remedial
      programme for recidivist drink drivers, the New South Wales Sober Driver
      Programme (SDP). SDP combines educational components and elements of group
      cognitive behavioural therapy in relation to drink driving behaviour. It is
      delivered in conjunction with punitive sanctions. DESIGN AND METHODS: The
      evaluation design included a comparison of recidivism rates over 2 years for SDP
      participants and a community control group of convicted drink drivers who
      received legal sanctions alone. Quantitative and qualitative surveys of SDP
      participants were also conducted before, immediately after and 4 months after the
      programme. Outcome measures included recidivism, change in participant knowledge
      and attitudes, self-reported behavioural intentions and skill development.
      RESULTS: SDP participants were 43% less likely to re-offend over 2 years compared
      with community controls who had received sanctions alone. Survey respondents
      demonstrated improved knowledge, attitudes and skills regarding drink driving.
      DISCUSSION AND CONCLUSIONS: SDP appears to be an effective intervention,
      demonstrating greater reductions in recidivism when compared with legal sanctions
      alone.

PMID- 18034384
TI  - Evaluation of a community-driven preventive youth initiative in Arnhem Land,
      Northern Territory, Australia.
AB  - INTRODUCTION AND AIMS: We evaluated a community-driven initiative established to
      prevent substance misuse and increase respect for culture and their elders among
      young people in a group of remote Aboriginal communities in Arnhem Land, Northern
      Territory (NT), Australia. The Youth Development Unit provided a range of
      training, recreational and cultural activities within a community development
      framework to all young people in the community. DESIGN AND METHODS: Methods of
      operation, community acceptability, perceived impact and likely ability to meet
      goals were assessed. Data included community, staff and stakeholder interviews
      and observation. School attendance, youth apprehension rates and information on
      levels of substance use were compared 2 years before and after the initiative was
      implemented. RESULTS: Interviewees reported increased youth training and
      recreational opportunities, increased communication between local agencies,
      overall satisfaction with programme delivery and optimism that it could achieve
      its goals. Suggested improvements included even more training, cultural
      programmes and other activities and employment of more community-based Indigenous
      staff. The importance of key staff, involvement of a respected Indigenous staff
      member and community engagement were noted as probable contributors to its
      success. DISCUSSION AND CONCLUSIONS: Indigenous young people in Australia remain
      one of the most disadvantaged and vulnerable groups. Community-driven preventive
      initiatives offer enhanced youth resilience and connectedness in remote
      Aboriginal communities and alternatives to substance use.

PMID- 18034385
TI  - Quality of life, depression and anxiety in alcohol dependence.
AB  - INTRODUCTION AND AIMS: Quality of life is recognised increasingly as an important
      component in the evaluation of disease processes. Comorbid psychiatric diagnoses
      accompanying alcohol addiction, especially severe cases of anxiety or depression,
      may have a negative impact on quality of life. This study focused on the impact
      of severity of anxiety and depression on quality of life of 150 alcohol-dependent
      patients treated in hospital. DESIGN AND METHODS: Consecutive patients were
      evaluated using relevant quality of life scales at the study's onset and 3 and 6
      weeks after the complete disappearance of withdrawal symptoms. Patients were
      classified into three groups: patients with alcohol dependence only, patients
      with depression and patients with anxiety. RESULTS: The level of anxiety and
      depression decreased from the initial evaluation to week 3 in patients with a
      high level of anxiety and depression, whereas the level of anxiety increased in
      the alcohol only-dependent patients. Initial evaluation conducted using the
      quality of life scales indicated significant differences between the three
      patient groups: physical health (F = 7.92, p = 0.001); psychological (F = 32.21,
      p = 0.001); social relationship (F = 3.45, p = 0.03); and environment (F = 7.79,
      p = 0.001). At weeks 3 and 6, quality of life for physical health, psychological
      and environment areas differed significantly between patient groups, but social
      relationships did not. At weeks 3 and 6, quality of life was lowest in patients
      with depression and highest in alcohol only-dependent patients with a low
      severity of depression or anxiety. DISCUSSION AND CONCLUSIONS: Symptoms of
      anxiety and depression accompanying alcohol addiction lead to an increase in
      severity of the problems associated with the addiction and have a negative effect
      on quality of life. Measurement of quality of life within the scope of treatment
      programmes would help to identify treatment requirements in addicted patients.

PMID- 18034386
TI  - The role of drug and alcohol policy in reducing Indigenous over-representation in
      prison.
AB  - Australian Indigenous imprisonment rates are higher now than they were at the
      time of the Royal Commission into Aboriginal Deaths in Custody. The Commission
      attributed Indigenous imprisonment to Indigenous cultural, economic and social
      disadvantage. Noel Pearson has argued that Indigenous drug and alcohol use is a
      more important cause of Indigenous contact with the justice system than
      Indigenous disadvantage. In this paper I argue that the available evidence
      provides strong support for Pearson's view and for the proposition that future
      efforts to reduce Indigenous imprisonment should place more emphasis on supply
      side strategies for reducing Indigenous drug and alcohol abuse.

PMID- 18034387
TI  - Harm reduction programmes in the Asia--Pacific Region.
AB  - INTRODUCTION AND AIMS: This paper reports on the public health intervention of
      harm reduction to address drug use issues in the Asia-Pacific region. DESIGN AND
      METHODS: It is based on the report 'Situational analysis of illicit drug issues
      and responses in Asia and the Pacific', commissioned by the Australian National
      Council on Drugs Asia Pacific Drug Issues Committee. A comprehensive desk-based
      review based on published and unpublished literature and key informant data.
      RESULTS: Drug use in the Asia--Pacific region is widespread, resulting in serious
      adverse health consequences. Needle and syringe programmes are found in some
      parts of Asia, but not in the six Pacific Island countries reviewed. Outreach and
      peer education programmes are implemented, but overall appear minor in size and
      scope. Substitution therapy programmes appear to be entering a new era of
      acceptance in some parts of Asia. Primary health care specifically for drug users
      overall is limited. DISCUSSION AND CONCLUSIONS: Harm reduction programmes in the
      Asia--Pacific region are either small in scale or do not exist. Most programmes
      lack the technical capacity, human resources and a limited scope of operations to
      respond effectively to the needs of drug users. Governments in this region should
      be encouraged to endorse evidence-based harm reduction programmes.

PMID- 18034388
TI  - The detection of illicit drugs in oral fluid: another potential strategy to
      reduce illicit drug-related harm.
AB  - As many of the harms associated with drug use may be due to intoxication,
      particularly where the individual is driving, operating machinery or involved in
      other tasks requiring high level psycho-motor functioning, it follows that having
      a valid, reliable convenient measure of recent drug use and, if possible,
      intoxication, will be important in reducing drug-related harm. Oral fluid testing
      is the latest technology offering promise in this area. As with any such
      technology, it has advantages and disadvantages. In this Harm Reduction Digest,
      Dyer and Wilkinson describe the technology, its strengths and limitations and
      provide examples of where it is currently being employed in practice. This is a
      must read paper for those of us interested in reducing drug-related harm.

PMID- 18034390
TI  - Obstructive sleep apnoea, renal sodium handling, arterial blood pressure and body
      mass index.

PMID- 18034392
TI  - RNA and protein clean-up from the same specimen. Comparison between the Qiagen
      and Ambion protocols.
AB  - Study of gene and protein expression patterns is considered desirable for gaining
      new insight into cellular molecular mechanisms. The purpose of the present study
      was to compare the RNeasy (Qiagen) and PARIS (Ambion) protocols for protein and
      RNA clean-up. We found that the RNeasy protocol resulted in a significantly
      higher yield of both RNA and protein compared to the PARIS protocol. Western blot
      analysis of proteins isolated with these two methods, and with use of three
      different antibodies (PKB/Akt, c-fos and CREM), indicated that these methods were
      equal in regard to protein patterns, despite the protein precipitation step that
      is included in the RNeasy protocol. In some cases, Western blot performed on
      unprecipitated flow-through (Qiagen) may be satisfactory for Western blot
      analysis, but the amount of protein is probably decisive for detection.

PMID- 18034391
TI  - Fecal levels of leukocyte markers reflect disease activity in patients with
      ulcerative colitis.
AB  - OBJECTIVE: A prominent feature of inflammatory bowel disease (IBD) is the
      presence of inflammatory cells in the gut mucosa, and which contribute to the
      ongoing inflammatory process. The aim of the study was to evaluate fecal
      neutrophil, eosinophil, mast cell and macrophage markers in the assessment of
      disease activity in patients with ulcerative colitis (UC). METHODS: Twenty-eight
      patients with active UC; 4 with proctitis, 16 with left-side colitis and 8 with
      total colitis, were included in the study. Patient history, endoscopy and
      histopathology were examined and fecal and serum samples were evaluated at
      inclusion and after 4 and 8 weeks of treatment. Fecal samples were analysed for
      myeloperoxidase (MPO), eosinophil protein X (EPX), mast cell tryptase, IL-1beta
      and TNF-alpha using immunoassays. Blood samples were analysed for MPO, EPX, C
      reactive protein, orosomucoid and leucocyte counts. RESULTS: Fecal MPO and IL
      1beta levels were elevated in all patients at inclusion despite different disease
      extensions. Striking reductions in fecal levels of MPO, EPX, tryptase and IL
      1beta were observed after 4 weeks of treatment in 20/28 patients with complete
      remission after 8 weeks. No further reductions were seen in 20/27 patients at 8
      weeks. Endoscopic score correlated to IL-1beta at all visits (p<0.01), to MPO at
      visits 2 and 3 (p<0.05, p<0.001), EPX at visit 2 (p<0.05) and tryptase at visit 3
      (p<0.01). Levels of fecal markers also related to histological indices of the
      disease. CONCLUSIONS: Measurements of fecal MPO, EPX and IL-1beta could be
      objective complements to endoscopical and histopathological evaluations in the
      daily care of patients with UC.

PMID- 18034394
TI  - [Legal aspects of ophthalmological expert assessment].

PMID- 18034395
TI  - [Endothelial dysfunction of central retinal vessels: a prognostic parameter for
      diabetic retinopathy?].
AB  - BACKGROUND: Endothelial dysfunction as a possible prognostic parameter seems to
      play a role in the course of diabetic retinopathy. Flicker-induced endothelial NO
      release may be used as an indicator for endothelial functionality of the central
      retinal vessels. METHODS: Flicker-induced arterial vasodilation as well as
      complete internal medicine status were determined in 65 type 1 and 170 type 2
      diabetics. Diabetic retinopathy was classified according ETDRS criteria.
      Furthermore, a group of 55 healthy subjects was used as control group. RESULTS:
      Diabetic subjects showed with 2.1+/-2.2 (type 1) and 2.2+/-2.4 (type 2) a
      significantly decreased percent arterial vasodilation in comparison to healthy
      subjects (3.6+/-2.1; p<or=0.001). With increasing stage of the diabetic
      retinopathy dilation of the retinal arterioles decreased significantly (p=0.002)
      while static arterial measurements before flicker testing did not show
      significant differences in the different stages of diabetic retinopathy. Diabetic
      patients without retinopathy already showed a noticeably reduced arterial
      dilation in comparison to healthy controls. These changes could be seen both in
      type 1 and type 2 diabetics. Patients with type 1 diabetes with proliferative
      diabetic retinopathy showed a mean percent dilation of 1.80+/-2.11, while these
      reactions had nearly disappeared in patients with type 2 diabetes (0.31+/-1.08).
      CONCLUSIONS: Both type 1 and type 2 diabetics showed significantly decreased
      flicker-induced arterial dilation as a sign of endothelial dysfunction in
      comparison to healthy controls. With increasing stage of the diabetic retinopathy
      dilation of the retinal arterioles decreased significantly. Diabetics without
      retinopathy already showed decreased flicker-induced reactions in comparison to
      healthy controls. Measurement of arterial flicker response may be useful for
      prognostic approaches in the case diabetes care.

PMID- 18034396
TI  - [Comparison of the corneal thickness as measured by Visante anterior segment OCT
      versus ultrasound technique].
AB  - BACKGROUND: Pachymetry is important in relation to the intraocular pressure (IOP)
      and can either be contact measured or non-contact measured. Depending on the
      corneal thickness it is possible to get false IOP measurements up to +/-5 mmHg.
      Thus, it is necessary to know the exact corneal thickness. A new non-contact
      technique for measuring the corneal thickness is available with the Visante
      anterior segment optical coherence tomography (OCT, Zeiss). METHODS: Ultrasound
      as well as the OCT technique is based on beam reflection at optical interfaces.
      Ultrasound waves or, respectively, coherent light beams (electromagnetic waves)
      are used for the imaging. Twenty-six patients were examined using the OCT and
      ultrasound with special emphasis on the corneal thickness and the results
      compared. RESULTS: The use of OCT to measure the corneal thickness is a safe
      method. Both techniques give comparable pachymetry results, whereas the OCT
      technique shows a tendency for lower values. Statistically significant
      differences could not be shown. CONCLUSION: OCT is a new, non-contact technique
      for measuring the corneal thickness. Furthermore, this is a method that does not
      interact with other measurements like keratometry or corneal topography.

PMID- 18034397
TI  - [On the effectiveness of the postsurgical mono- or combination therapy after
      cataract operations].
AB  - BACKGROUND: In postoperative inflammatory diseases of the anterior segment of the
      eye the cause of the inflammation on the one hand and symptoms on the other hand
      have to be treated. Exactly this target can be reached by a combination of the
      active ingredients dexamethasone and gentamicin. In the present study we compared
      a fixed combination therapy with the consecutive application of the same
      substances. PATIENTS AND METHODS: We examined the effectiveness and handling of a
      fixed combination in a prospective, single-masked, randomised, comparing,
      controlled parallel group design study in comparison with a separate application
      of dexamethason and gentamicin sulfate in cataract patients. The main target
      criteria was the postoperative inflammation measured by of the laser-flare meter
      and clinical parameters. In addition different investigations were accomplished
      for the estimation of the compliance and the subjective tolerability. RESULTS:
      There was a significantly lower inflammation rate measured by the Tyndall value
      and the clinical examination on days 7 and 14 after cataract surgery on applying
      the combined medicinal product in comparison to applying the same active
      ingredients but in separate eye drops. CONCLUSIONS: Patients receiving the fixed
      combination will have advantages compared to those patients receiving the active
      ingredients as single agent therapy. A major advantage of a combined medicinal
      product is the lack of a wash-out effect with the combination therapy. Therefore,
      such a therapeutic possibility should chosen for ophthalmological patients.

PMID- 18034398
TI  - [Ultrasound biomicroscopic diagnosis of scleral foreign bodies].
AB  - BACKGROUND: Small intrascleral foreign bodies of different materials, especially
      plastic or organic, can sometimes not easily--or not at all--be detected by
      routine X-ray examination or computed tomography scan. The aim of our study was
      to evaluate the usefulness of ultrasound biomicroscopy (UBM) with regard to the
      detection and localisation of such foreign bodies. METHODS: An in vitro study
      with the preparation of a scleral tunnel on 12 porcine eyes was performed. Small
      foreign bodies of different types of material were placed in the tunnel. The UBM
      was performed with a Humphrey Ultrasound Biomicroscope, Model 840, to evaluate
      its diagnostic value in detecting and specifying these sclera-covered foreign
      bodies. RESULTS: Even small foreign bodies of the anterior ocular segment of only
      200 microm in size can be detected with the UBM due to the typical ultrasound
      patterns and artifacts. However, there is no diagnostic specificity for the
      corresponding material. CONCLUSION: The UBM is a high-frequency ultrasonic device
      with an imaging depth of 5 mm and a spatial resolution of 100 microm. Therefore
      it is a useful alternative or, respectively, additional diagnostic tool to common
      imaging techniques like routine X-ray imaging or CT scans, especially in the
      detection of non-metallic objects. It can provide important information for the
      ophthalmic surgeon with regard to pre-operative evaluation of the eye.
      Furthermore, the UBM might even substitute operative exploration of foreign
      bodies if they are located in the anterior segment of the eye.

PMID- 18034399
TI  - [Ophthalmodynamometry in the diagnostics of Grave's ophthalmopathy].
AB  - BACKGROUND: Since endocrine orbitopathy is characterised by exophthalmos and
      increased orbital tissue pressure which may lead to a compression of and damage
      to the optic nerve, it was the purpose of this study to evaluate whether the
      increased orbital tissue pressure in endocrine orbitopathy is associated with an
      elevated central retinal vein pressure as estimated by ophthalmodynamometry, and
      whether the central retinal vein pressure changes in the course of the disease.
      PATIENTS AND METHODS: The prospective clinical study included 7 patients (13
      eyes) with endocrine orbitopathy. They were screened for the prevalence of a
      spontaneous pulsation of the central retinal vein. In case of a missing
      spontaneous pulse, the collapse pressure of the central retinal vein was
      estimated by a modified ophthalmodynamometry using a corneal contact lens
      associated ophthalmodynamometric device. A group of 122 patients (156 eyes)
      without orbital or retinal diseases served as control group. RESULTS: The
      frequency of a spontaneous pulse of the central retinal vein was significantly
      lower in the study group (1/13 or 8%) than in the control group (121/156 or 78%
      p<0.001; odds ratio: 41.5). The central retinal vein collapse pressure as
      determined by ophthalmodynamometry was significantly higher in the study group
      (22.7+/-19.5 arbitrary units) than in the control group (4.7+/-12.8 arbitrary
      units) (p=0.002). For one patient with 7 examinations during a follow-up of 16
      months, the central retinal vein pressure increased from 17 arbitrary units to 56
      units, and decreased to 14 to 19 arbitrary units after initiation of a systemic
      therapy and regression of the exophthalmos. Three years later a spontaneous
      pulsation of the central retinal vein was detectable. CONCLUSION:
      Ophthalmodynamometry may be a useful examination for the indirect assessment of
      the orbital tissue pressure in patients with endocrine orbitopathy.

PMID- 18034400
TI  - [Ophthalmodynamometry of central retinal vein collapse pressure in idiopathic
      intracranial hypertension].
AB  - BACKGROUND: The diagnosis of idiopathic intracranial hypertension results from a
      synopsis of standardised examinations including MRI. Since the cerebrospinal
      fluid pressure influences the pressure of the central retinal vein, it was the
      purpose of the present study to evaluate whether the ophthalmodynamometric
      estimation of the central retinal vein collapse pressure is helpful for the
      diagnosis of idiopathic intracranial hypertension. PATIENTS AND METHODS: The
      study included 5 patients with idiopathic intracranial hypertension with a mean
      age of 38.3+/-10.8 years and 88 subjects of a control group with a mean age of
      66.8+/-13.1 years. Using a modified corneal contact lens-associated
      ophthalmodynamometry, the collapse pressure of the central retinal vein was
      estimated. RESULTS: The central retinal vein collapse pressure was significantly
      higher in the study group (33.0+/-27.3 relative units) than in the control group
      (2.0+/-6.7 relative units) (p<0.006; 95 % confidence interval: -11.5, 50.5). The
      central retinal artery collapse pressure did not vary significantly between the
      two groups (52.7+/-15.3 relative units versus 65.6+/-20.4 relative units; p=0.19;
      95 % confidence interval: -36.6, 10.5). CONCLUSIONS: The corneal contact lens
      associated ophthalmodynamometry can be helpful for the monitoring of patients
      with intracranial idiopathic hypertension.

PMID- 18034401
TI  - [Corneal dellen secondary to conjunctival chemosis following transconjunctival
      orbital decompression].
AB  - BACKGROUND: Transconjunctival orbital decompression ("swinging eyelid technique")
      nowadays is the technique of choice for the reduction of proptosis in Graves'
      orbitopathy. Here, we present the first report of two patients who developed
      corneal dellen secondary to conjunctival chemosis following swinging eyelid
      decompression. CASE REPORTS: Two female patients, 38 and 52 years old, underwent
      transconjunctival orbital decompression in 2006. Postoperatively, they developped
      corneal dellen secondary to conjunctival chemosis. The dellen and the chemosis
      completely regressed after intensive topical and oral therapy. CONCLUSION:
      Corneal dellen represent a potential cause of postoperative pain following
      transconjunctival orbital decompression.

PMID- 18034402
TI  - [Bilateral uveal melanoma: a case report].
AB  - BACKGROUND: The occurrence of bilateral uveal melanoma is rare. This is the first
      reported case of bilateral melanoma of the choroidea in Austria. METHODS: The
      chart of a 62-year-old male patient with bilateral melanoma of the choroidea was
      reviewed. RESULTS: In October 1992, a patient was diagnosed with a choroidal
      melanoma in the left eye. After two treatments with a ruthenium applicator in
      1992 and 1995, the left eye was enucleated in 1999 due to recurrent growth of the
      choroidal melanoma. In September 2005, the patient presented with a primary
      choroidal melanoma in the remaining right eye. Sonography of the liver as well as
      CCT and bone marrow scintigraphy showed no sign of metastatic disease. A
      ruthenium-106 brachytherapy was performed and the size and height of the melanoma
      showed decreases. In July 2006, the patient developed metastatic disease and died
      the following month due to metastasis of the liver. In the genetic analysis,
      monosomy 3 was detected in both melanoma, an amplification of c-MYC of chromosome
      8 was detected in the melanoma of the right eye only. CONCLUSION: Bilateral uveal
      melanoma is a rare diagnosis. This case shows the importance of a thorough and
      recurrent examination of the second eye. The results of the genetic analysis are
      discussed.

PMID- 18034403
TI  - [Solar retinopathy: follow-up examinations with optical coherence tomography
      (OCT) and microperimetry].
AB  - BACKGROUND: Solar retinopathy is a phototoxic damage to the central retina. It
      may cause visual deterioration and a central scotoma with reading difficulties,
      that usually fade with time. Morphological and functional changes can be very
      subtle and are often inadequately detected by standard examinations. PATIENTS AND
      METHODS: The more affected, left eye of a 41-year-old female patient was examined
      clinically, by optical coherence tomography (OCT 3) and by MP 1-microperimetry
      during a 6-month follow up after gazing at a partial eclipse. RESULTS: At all
      times visual acuity was reduced to 0.7 causing visual deterioration. OCT
      examinations showed a subfoveal damage of decreasing extent, which was still
      detectable after 6 months. The retinal affection resulted in a persistent
      microscotoma of decreasing depth. CONCLUSION: OCT 3 and MP 1-microperimetry are
      able to detect the morphological and the functional damages in solar retinopathy
      at a level of sensitivity good enough to produce correlating results which allow
      the detection of subtle changes during follow-up.

PMID- 18034404
TI  - [Traumatic dislocation of the globe into the maxillary sinus--is a rehabilitation
      possible?].
AB  - BACKGROUND: The complete traumatic dislocation of the globe into the maxillary
      sinus after orbital floor fractures is a very rare event. It results from direct
      transmission of a traumatic force which impinges the orbital frame or may result
      from an increasing pressure to the orbital contents. Diplopia or evidence of a
      displaced globe necessitates an exploration and reconstruction of the orbital
      floor. CASE REPORT: A 62-year-old male was admitted to our hospital because of a
      blunt injury to the orbital region caused by a machine for planing timber. On
      examination the patient had a massive right periorbital haematoma and no globe
      was visibly found. The CT scan revealed a blow-out fracture of the orbital floor
      with a complete dislocation of the right globe into the right maxillary sinus.
      Using a bright flashlight on the right maxillary region the patient reported
      light perception. The operative exploration showed no impaired integrity of the
      globe, no apparent laceration of the orbital muscles and a preserved continuity
      of the optic nerve. The dislocated globe was repositioned manually into the orbit
      and secured by an antral balloon catheter. CLINICAL COURSE: Postoperative
      magnetic resonance imaging showed a correct anatomic status. The muscles did not
      seem to be lacerated and the continuity of the optic nerve was demonstrated.
      Incarcerations were not existent. 9 months postoperatively the vision recovered
      to 1.0 p. The motility was slightly diminished (elevation and abduction 20
      degrees, adduction 25 degrees and downwards 20 degrees over midline). The patient
      suffered from diplopia when looking 25 degrees to the right and 20 degrees
      upwards. The anisocoria with a slight dilation of the pupil had declined in the
      right eye but was still present. CONCLUSION: This case of complete dislocation of
      the globe into the maxillary sinus demonstrates that only few injuries may result
      and that after operative reconstruction of the orbital floor a good functional
      result can achieved.

PMID- 18034405
TI  - [Ceremonial lecture on the occasion of DOG in Berlin, 2007].

PMID- 18034406
TI  - [Health technology assessment in the dialysis setting. Proceedings of the 2nd
      Lucera Nephrology Seminar, Lucera, Italy, 2007 March 2].

PMID- 18034407
TI  - [Health technology assessment].
AB  - Health technology assessment (HTA) provides information about the effectiveness,
      costs and broader impact of health technologies to those who plan, administer or
      receive care in the national health system. ''Technology'' includes all
      interventions used to promote health, prevent and treat disease, and improve
      rehabilitation and long-term care. An HTA program addresses the questions to
      which patients and the national health systems need answers, by investigating
      four main factors: whether the technology (intervention) works, for whom and at
      what cost, and how it compares with alternatives. Health technology assessment is
      not simply another kind of research. It has a number of key features that are
      critical to its ongoing impact and distinguish it from research: it is policy
      oriented, it is interdisciplinary in its content and procedures, it summarizes
      information from databases/reviews and sometimes produces original data;
      moreover, those engaged in health technology assessment recognize the importance
      of disseminating and communicating the information acquired. Health technology
      assessment constitutes a bridge between the world of research and the world of
      decision-making, particularly policy-making, in health care.

PMID- 18034408
TI  - [Health technology assessment: focus on hemodialysis equipment].
AB  - INTRODUCTION: The problem of the assessment of electromedical equipment and in
      particular hemodialysis machines, an important compartment of medical technology,
      is described here. The typical ''system'' approach is employed, which includes
      not only the extent to which the equipment meets legal and technical standards,
      but also proper training and updating of the personnel operating the machines.
      METHODS: The main risk factors of hemodialysis machines are identified not only
      in relation to safety but also performance, which could have a direct impact on
      safety. RESULTS: Some technical aspects are introduced which play a fundamental
      role in maintaining the principal characteristics of safety and performance and
      in guaranteeing proper risk analysis from the standpoint of both manufacturer and
      user. Also the importance of the professionals involved in the use of such
      equipment, as well as those who have to manage their correct and safe employment
      is underlined. CONCLUSIONS: The technological progress that characterizes this
      important field of application will certainly in the future create the
      possibility of a more ''personalized'' dialysis with greater therapeutic efficacy
      and fewer side effects. This will, however, require continuous updating of the
      professionals using the equipment and maintaining it in optimal safety and
      performance conditions. The professional figure of the clinical engineer is a key
      element in meeting these objectives, also on the basis of the experience gained
      at an international level.

PMID- 18034409
TI  - [Health-care costs and health technology assessment].
AB  - This paper is made up of four sections: a) an overview of the relationship
      between health-care costs and health technology assessment; b) the state of art
      of the research into health technology assessment with details on the main fields
      of research, the results obtained, and the gaps to be bridged; c) an analysis of
      the techniques for assessing health-care technology (cost-minimization analysis
      [CMA]; cost-effectiveness analysis [CEA]; cost-utility analysis [CUA]; cost
      benefit analysis [CBA]); and d) an overview of the use of the four assessment
      techniques between 1980 to 2006 in nephrology, with special emphasis on dialysis.

PMID- 18034410
TI  - [Doctor or technician? Reflections on the medical professional today].
AB  - Medicine is an outstanding example of an empirical science in theory and
      practice. In every stage of his work a doctor should be ready to pick up signs of
      possible scientific progress. Being constantly attentive and able to see anything
      new occurring, however difficult it may be to discern, should remain the basis of
      any professional commitment that takes care not to become sterile and thereby
      less effective in treating disease. A doctor is an experimenter par excellence,
      one who constantly applies experimental methods based on his own ''historical''
      knowledge, experience, and capacity to comprehend even the tiniest signals that
      reach him from the real world. On the other hand, although the indiscriminate
      acceptance of results obtained by clinical trials and the increasing recourse to
      technology could herald the end of clinical freedom, we believe that such
      recourse to technology is, in fact, desirable. The reason for this belief is that
      a lack of innovation leads to loss of enthusiasm and loss of interest in specific
      clinical problems; it also results in a cultural attitude that refutes the notion
      of experimental logic being inherent in any treatment because of the
      changeability of individual conditions on a biological, clinical, and psycho
      relational level.

PMID- 18034411
TI  - [Evaluation of peritoneal catheters and connection systems in peritoneal
      dialysis].
AB  - Evaluation of peritoneal catheters is based on the material, the number and type
      of cuffs, the length and intraperitoneal shape of the catheter, and its site of
      insertion. Final cost is another important issue which should take into account
      differences in the incidence of complications, in the number of hospitalizations,
      and in the simplicity of catheter insertion. Double-cuff catheters are used more
      than single-cuff catheters. The most commonly used catheter shapes are the
      classical Tenckhoff, the swan neck, the coil, and self-locating catheters. The
      latter are more expensive than Tenckhoff catheters but seem to offer some
      advantages, even if not sustained by adequate controlled trials so far. In
      addition, placement of these catheters may require different techniques or skills
      compared to the classical Tenckhoff. The most recent Italian guidelines based
      only on grade 1 and 2 evidence exclude that the type of catheter may influence
      the infection rate. There are no data from prospective controlled studies to
      evaluate the incidence of mechanical complications, hospitalization and technique
      survival. With regard to dialysis systems, it is still unclear if new plastic
      materials may offer any advantage over PVC. There is grade 1 evidence that Y-set
      and double-bag systems reduce the peritonitis rate compared to standard 1-way
      systems. The available data do not indicate significant differences in the
      incidence of peritonitis using Y-set compared with double-bag systems. The higher
      cost of double-bag systems is counteracted by shorter and easier training and by
      better acceptance by the patients.

PMID- 18034412
TI  - [Assessment of APD cyclers].
AB  - Automated peritoneal dialysis (APD) is a home treatment that allows exchanges to
      be performed during the night by means of a mechanical device (cycler). The most
      important requirements of a cycler are a user-friendly intuitive interface,
      safety in usage, noiselessness and full portability. These characteristics
      influence patient satisfaction and consequently patient compliance with dialysis
      treatment. Other important features of the device are online pressure and flow
      sensors to avoid damage to the peritoneum, control of inflow and outflow rates,
      and flexibility in performing different treatment schedules. Today's cyclers
      allow all these functions and appear to respond well to the current clinical
      requirements. Another advantage of cyclers is that they can store treatment data
      on memory cards and send information about home APD treatment to the dialysis
      center. However, these systems use specific software developed by their
      manufacturers and do not interact with software of other producers nor with the
      most common databases; moreover, the data cannot be uploaded to hospital files.
      The availability of open software for cyclers allowing data to be exported to
      common database formats would enable us to compare different APD systems. A
      future goal might therefore be the integration of different APD software systems
      into a global standard.

PMID- 18034413
TI  - [Hemodialysis monitor assessment].
AB  - The choice of a dialysis monitor should be based on a thorough evaluation of
      multiple factors. The nephrologist must take into account not only the technical
      features of the device, but also aspects related to the operating environment,
      the organization of the dialysis unit, and the number and expertise of the
      nursing staff under his supervision. The enormous technological developments of
      recent years have contributed to a considerable improvement in the survival and
      quality of life of patents on chronic hemodialysis. Nevertheless, the issue of
      device flexibility and sophistication, today supported also by a high grade of
      safety thanks to the widespread use of electronics in the prescription, control
      and automatic feedback regulation of dialysis parameters, needs to be addressed
      with proper knowledge of the device and requires adequate training of nursing
      personnel. In addition to the knowledge of the basic technical features, it is
      very important to test the device in the clinical setting, where also the
      opinions of nurses play an important role. The ''partnership'' between
      nephrologists and industry, based on a bilateral exchange of ideas and
      experimental studies, still provides excellent results concerning new
      technological applications coupled with improvements in patient tolerance,
      survival and quality of life, further emphasizing the role of the nephrologist in
      properly evaluating these very complex devices.

PMID- 18034414
TI  - [Assessment of dialysis membranes].
AB  - The paper considers the aspects that play a role in the technological assessment
      of dialysis membranes: transport mechanisms (diffusion, convection and
      adsorption) and biocompatibility. An attempt is made to clarify how they relate
      to the performance of a dialysis session and which are the best parameters to
      compare the efficiency of different membranes. The study does not offer
      definitive solutions to such a delicate and complicated matter but suggests some
      points for discussion. In conclusion, the performance of a membrane is a very
      difficult process to evaluate and different membranes can be compared only by
      establishing adequate points of comparison. At the same time, the points of
      comparison themselves may change depending to the type of comorbidities of the
      specific patient considered for membrane selection.

PMID- 18034415
TI  - [Automatic system control and its application in dialysis].
AB  - The progressive increase in the mean age of dialysis patients associated with
      increasing comorbidity factors such as the presence of cardiovascular disease and
      diabetes have significantly worsened patients' clinical status and tolerance to
      hemodialysis. On the other hand, the demand for short treatment times increases
      the risk of hemodynamic instability as well as inadequate depuration. The
      traditional management of the dialysis session by setting predefined treatment
      parameters and carrying out active therapeutic intervention only in the event of
      complications is definitely unsuitable for short-lasting treatments, which are
      often complicated by hemodynamic instability, especially in critically ill
      patients. The first step in improving the management of the dialysis session is
      the use of uninvasive systems for continuous monitoring of the hemodynamic and
      biochemical parameters that characterize dialysis quality. In the last decade,
      special sensors have been designed for continuous measurement of blood volume,
      blood temperature, blood pressure, heart rate and electrolytes. As a second step,
      some of these devices have been interfaced with the dialysis equipment, mainly
      with a view to preventing cardiocirculatory instability but also monitoring the
      efficiency of dialysis (biofeedback control systems). The basic components of a
      biofeedback system are the plant, the sensors, the actuators, and the controller.
      The plant is the biological process we need to control, while the sensors are the
      devices used for measuring the output variables. The actuators are the working
      arms of the controller. The controller is the mathematical model that
      continuously sets the measured output variable against the reference input and
      modifies the actuators in order to reduce any discrepancies. In actual practice,
      however, there are a number of conceptual, physical and technological
      difficulties to overcome. In particular, the behavior of what is to be controlled
      may be nonlinear and time-varying, with interactions between the actuators and
      the controlled variable. In such cases, more sophisticated control systems are
      needed that must be capable of identifying the behavior of the process and
      continuously update information data while the control is on. These complex
      systems are called adaptive controllers. At present, there are three biofeedback
      systems routinely used in clinical dialysis. All of them are aimed at improving
      the cardiovascular stability during hemodialysis, which at present is one of the
      main problems limiting the tolerance to treatment on the one hand and the quality
      of hemodialysis on the other. These systems include biofeedback control of blood
      volume, biofeedback control of thermal balance, and biofeedback control of blood
      pressure.

PMID- 18034416
TI  - [Nanotechnology and nephrology].
AB  - Nowadays, nanotechnology and microfluidic technologies are emerging as enabling
      factors for the operation of lab-on-chip devices and micro total analysis systems
      in the biotechnological and biomedical fields. These devices allow to reduce the
      waste of reagents and products, and to increase analytical precision and
      operational throughput. The field of nanotechnology is introduced in this paper
      and some manufacturing methods at the nanometer and micrometer scale are
      presented, together with their potential application in producing biomedical
      devices for filtration and solute elimination. Examples will include electron
      beam lithography, soft lithography, and electrospinning of nanofiber scaffolds
      for tissue engineering.

PMID- 18034417
TI  - [Biofilters and biosensors].
AB  - Sepsis is the leading cause of morbidity and mortality in intensive care units
      (ICU). Acute renal failure (ARF) is a common condition, affecting approximately
      5% of all hospitalized patients and up to 20% of critically ill patients. The
      combination of ARF and sepsis is associated with 75% mortality. Hyperglycemia and
      an increase in plasma lactate concentration are markers of poor prognosis in
      patients with sepsis; they often precede the onset of multiple organ dysfunction
      and ARF. Direct online measurement by means of amperometric biosensors would
      allow the early detection of increasing levels of both glucose and lactate, as
      well as the possibility to maintain glucose within a well-defined range. Current
      standards of care in ARF require synthetic membranes that substitute the small
      solute clearance function of the renal glomerulus, but they do not replace the
      transport, metabolic and endocrine functions of the renal proximal tubule cells.
      The application of cell therapy to the successful process of hemofiltration may
      therefore improve the poor prognosis of patients with ARF in the ICU. An
      extracorporeal bioartificial kidney consisting of a conventional hemofilter
      connected to a renal tubule assist device has demonstrated both in animal models
      of ARF and in phase I/II clinical trials its ability to successfully replace the
      filtration, transport, metabolic, and endocrine functions of the kidney. To
      improve the outcome of septic patients with ARF, multidisciplinary interactions
      and cooperation between basic, clinical and industrial researchers are mandatory;
      the development of new artificial or biological devices may allow online
      monitoring of biological parameters and better treatment of septic syndrome and
      related systemic complications.

PMID- 18034418
TI  - Manipulation of NK cytotoxicity by the IAP family member Livin.
AB  - Natural killer (NK) cells are part of the innate immune system, capable of
      killing tumor and virally infected cells. NK cells induce apoptosis in the target
      cell by either granule- or receptor-mediated pathways. A set of inhibitory and
      activation ligands governs NK cell activation. As transformed cells often attempt
      to evade NK cell killing, up-regulation of a potential anti-apoptotic factor
      should provide a survival advantage. The inhibitor of apoptosis protein (IAP)
      family can inhibit apoptosis induced by a variety of stimuli. We have previously
      described a new IAP family member, termed Livin, which has two splice variants
      (alpha and beta) with differential anti-apoptotic activities. In this study, we
      explore the ability of Livin to inhibit NK cell-induced killing. We demonstrate
      that Livin beta moderately protects against NK cell killing whereas Livin alpha
      augments killing. We show that Livin beta inhibition in Jurkat cells is apparent
      upon concomitant activation of an inhibitory signal, suggesting that Livin
      augments an extrinsic inhibitory signal rather than functioning as an independent
      inhibitory mechanism. Finally, we demonstrate that detection of both Livin
      isoforms in melanoma cells correlates with a low killing rate. To date, this is
      the first evidence that directly demonstrates the ability of IAP to protect
      against NK cell-induced apoptosis.

PMID- 18034419
TI  - Characterization of mouse CD4 T cell subsets defined by expression of KLRG1.
AB  - The mouse killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor
      known to be expressed on a subset of NK cells and antigen-experienced CD8 T
      cells. Here, we have characterized expression of KLRG1 on CD4+ T cells from
      normal mice. While a polyclonal TCR repertoire suggests thymic origin of KLRG1+
      CD4+ cells, KLRG1 expression was found to be restricted to peripheral CD4+ T
      cells. Based on phenotypic analyses, a minority of KLRG1+ CD4+ cells are
      effector/memory cells with a proliferative history. The majority of KLRG1+ CD4+
      cells are, however, bona fide Treg cells that depend on IL-2 and/or CD28 and
      express both FoxP3 and high levels of intracellular CD152. KLRG1-expressing Treg
      are contained within the CD38+ subset but are only partially overlapping with the
      CD25+ CD4+ Treg subset. In functional assays, KLRG1+ CD4+ cells were anergic to
      TCR stimulation with respect to proliferation, and sorted KLRG1+ CD25+ CD4+ cells
      were equal or superior to KLRG1+ CD25- CD4+ cells, which were more potent than
      KLRG1- CD25+ CD4+ cells in suppressing responder cell proliferation. Together,
      our results demonstrate that KLRG1 expression defines novel and distinctive
      subsets of senescent effector/memory and potent regulatory CD4+ T cells.

PMID- 18034420
TI  - Differential impact of the transcriptional repressor Gfi1 on mature CD4+ and CD8+
      T lymphocyte function.
AB  - The transcriptional repressor Gfi1 is a nuclear zinc-finger protein that is
      expressed in T cell precursors in the thymus, but is down-regulated in mature,
      resting T cells. Gfi1 expression rises transiently to levels seen in thymocytes
      upon antigenic activation. We show here that lack of Gfi1 causes delayed cell
      cycle entry and apoptosis after antigenic stimulation in both mature CD4+ and
      CD8+ T cells ex vivo. DNA micro-array analysis demonstrated that this correlated
      with an up-regulation of the death receptor CD95, the proapoptotic factors Bad
      and Apaf1 and the cell cycle inhibitor p21, and a down-regulation of Bcl-2
      expression in Gfi1-/- T cells. Surprisingly, while Gfi1-deficient CD4+ T cells
      showed the same defective behavior in vivo, Gfi1-deficient CD8+ T cells showed no
      aberration in vivo and were fully able to mount an anti-viral immune response.
      This indicates that Gfi1 exerts different functions in CD4+ and CD8+ T cells very
      likely by maintaining different genetic programs in both cell types, and appears
      to be essential for the CD4 helper T cell immune response but dispensable for the
      function of cytotoxic CD8+ T cells.

PMID- 18034421
TI  - Selective silencing of DNA-specific B lymphocytes delays lupus activity in
      MRL/lpr mice.
AB  - The pathological DNA-specific B lymphocytes in lupus are logical targets for a
      selected therapeutic intervention. We have hypothesized that it should be
      possible to suppress selectively the activity of these B cells in lupus mice by
      administering to them an artificial molecule that cross-links their surface
      immunoglobulins with the inhibitory FcgammaIIb surface receptors. A hybrid
      molecule was constructed by coupling the DNA-mimicking DWEYSVWLSN peptide to a
      monoclonal anti-mouse FcgammaRIIb antibody. This chimeric antibody was added to
      cultured spleen cells from sick MRL/lpr mice, immunized with diphtheria toxoid,
      resulting in reduction of the numbers of anti-DNA but not of anti-diphtheria IgG
      antibody-producing cells. Intravenous infusions with the DNA-peptide antibody
      chimera to 7-wk-old animals prevented the appearance of IgG anti-DNA antibodies
      and of albuminuria in the next 2 months. The administration of the DNA-peptide
      chimeric antibody to 18 wk-old mice with full-blown disease resulted in the
      maintenance of a flat level of IgG anti-DNA antibodies and in delay of the
      aggravation of the lupus glomerulonephritis. The use of chimeric antibodies
      targeting inhibitory B lymphocyte receptors represents a novel approach for the
      selective suppression of autoreactive disease-associated B cells in autoimmune
      diseases.

PMID- 18034422
TI  - TLR9 signaling is essential for the innate NK cell response in murine cutaneous
      leishmaniasis.
AB  - Mice deficient for the TLR adaptor molecule MyD88 succumb to a local infection
      with Leishmania (L.) major. However, the TLR(s) that contribute to the control of
      this intracellular parasite remain to be defined. Here, we show that TLR9 was
      required for the induction of IL-12 in bone marrow-derived DC by intact L. major
      parasites or L. major DNA and for the early IFN-gamma expression and cytotoxicity
      of NK cells following infection with L. major in vivo. During the acute phase of
      infection TLR9-/- mice exhibited more severe skin lesions and higher parasite
      burdens than C57BL/6 wild-type controls. Although TLR9 deficiency led to a
      transient increase of IL-4, IL-13 and arginase 1 mRNA and a reduced expression of
      iNOS at the site of infection and in the draining lymph nodes, it did not prevent
      the development of Th1 cells and the ultimate resolution of the infection. We
      conclude that TLR9 signaling is essential for NK cell activation, but dispensable
      for a protective T cell response to L. major in vivo.

PMID- 18034423
TI  - Regulation of constitutive and microbial pathogen-induced human macrophage
      migration inhibitory factor (MIF) gene expression.
AB  - The cytokine macrophage migration inhibitory factor (MIF) is an important
      regulator of innate immunity, inflammation and oncogenesis. However, four decades
      after its identification, the molecular mechanism(s) regulating the expression of
      the MIF gene remain largely unknown. Analyses of human monocytic (THP-1),
      epithelial (HeLa and A549) and keratinocytic (HaCat) cells transfected with wild
      type, truncated and mutated MIF promoter reporter constructs, and electrophoretic
      mobility shift assay, chromatin immunoprecipitation, and siRNA inhibition
      indicated that the transcription factors specificity protein (Sp)1 and cAMP
      response element-binding protein (CREB) are critical positive regulators of
      constitutive human MIF gene expression. Albeit located in a cytosine guanine
      dinucleotide island, the MIF gene was found to be hypomethylated, an observation
      consistent with high baseline transcriptional activity. Moreover, stimulation of
      THP-1 cells and of peripheral blood mononuclear cells with microbial products up
      regulated phosphorylated Sp1 nuclear content, Sp1 DNA-binding activity, MIF
      promoter activity and MIF mRNA levels in a MEK1/2-, Sp1-dependent manner. Taken
      together with previous observations of an important role for MIF in pro
      inflammatory macrophage responses, these present findings suggest a key role for
      Sp1 and CREB in transcriptional regulation of MIF gene expression and MIF
      dependent host antimicrobial innate immune defense.

PMID- 18034424
TI  - The activity of lipopeptide TLR2 agonists critically depends on the presence of
      solubilizers.
AB  - Lipoproteins activate cells of the innate immune system via heteromers of Toll
      like receptor (TLR) 2 with either TLR1 or TLR6. In spite of progress in
      understanding TLR-dependent signal transduction and the pathophysiological
      relevance of TLR2, the molecular basis of ligand recognition by this receptor is
      poorly defined. Here, we show that the bioactivity of lipopeptides (LP)
      critically depends on the dilution protocol and especially the presence of
      proteins or detergents acting as solubilizers. Fluorescence correlation
      spectroscopy of fluorescently labeled analogs of synthetic LP revealed that the
      LP form aggregates in solution. Dilution into protein- and serum-free buffers led
      to a complete loss of activity due to formation of large and highly heterogeneous
      aggregates. When dimethylsulfoxide stock solutions were diluted into BSA or serum
      containing buffers particles of strongly reduced size were obtained. For some LP,
      an intermediary dilution step either with tert.-butyl alcohol/H2O (4:1) or with
      octyl-beta-D-glucopyranoside further increased activity. For a panel of LP
      exhibiting very different activities when diluted directly into protein
      containing solutions, introduction of this dilution step resulted in comparable
      bioactivities. These results demonstrate the significance of solubilizing agents
      for the bioactivity of LP and are highly relevant for analyzing structure
      activity relationships of LP-dependent TLR2 activation.

PMID- 18034425
TI  - Defective Artemis nuclease is characterized by coding joints with microhomology
      in long palindromic-nucleotide stretches.
AB  - T-B-NK+ severe combined immunodeficiency (SCID) is caused by a defect in V(D)J
      recombination. A subset of these patients has a mutation in one of the non
      homologous end joining (NHEJ) genes, most frequently the Artemis gene. Artemis is
      involved in opening of hairpin-sealed coding ends. The low levels of residual DH
      JH junctions that could be amplified from patients' bone marrow precursor B cells
      showed high numbers of palindromic (P)-nucleotides. In 25% of junctions,
      microhomology was observed in the P-nucleotide regions, whereas this phenomenon
      was never observed in junctions amplified from bone marrow precursor B cells from
      healthy controls. We utilized this difference between Artemis-deficient cells and
      normal controls to develop a V(D)J recombination assay to determine hairpin
      opening activity. Mutational analysis of the Artemis gene confirmed and extended
      the mapping of an N-terminal nuclease active site, which contains several
      indispensable aspartate residues. C-terminal deletion mutants did not show such
      severe defects in the V(D)J recombination assay using transient overexpression of
      (mutated) Artemis protein. However, a C-terminal deletion mutation causes T-B-NK+
      SCID, indicating that the Artemis C terminus is essential for V(D)J recombination
      at the normal Artemis expression level. The V(D)J recombination assays used in
      this study contribute to the diagnostic strategy for T-B-NK+ SCID patients.

PMID- 18034426
TI  - Phenotypic analysis of human CD4+ T cells specific for immediate-early 63 protein
      of varicella-zoster virus.
AB  - Open reading frame 63 of varicella-zoster Virus (VZV) encodes an immediate early
      (IE) phosphoprotein (IE63) that is believed to be important for viral infectivity
      and establishing latency. Evidence suggests that VZV-specific T cells are crucial
      in the control of viral replication; however, data addressing the existence of
      IE63 protein-specific CD4+ T cells are limited. Using IFN-gamma immunosorbent
      assays, we identified high frequencies of responses to overlapping peptides
      spanning the IE63 protein both ex vivo and after in vitro restimulation in
      healthy VZV-seropositive individuals. We identified a commonly recognised
      epitope, restricted by HLA-DRB1*1501, which was naturally processed and presented
      by keratinocytes. We proceeded to investigate the frequency and phenotype of the
      epitope-specific CD4+ T cells using HLA class II tetrameric complexes. Epitope
      specific CD4+ T cells were detectable ex vivo and showed a mixed central and
      effector-memory differentiation phenotype, with a significant proportion showing
      evidence of recent activation and rapid effector function. In summary these data
      implicate persistent low-level or recurrent VZV antigen exposure in healthy
      immune donors and are compatible with a role for IE63-specific CD4+ T cells in
      the control of viral reactivation.

PMID- 18034427
TI  - Activation-induced cytidine deaminase induces DNA break repair events more
      frequently in the Ig switch region than other sites in the mammalian genome.
AB  - Activation-induced cytidine deaminase (AID) produces DNA breaks in immunoglobulin
      genes during antibody diversification. Double-stranded breaks (DSB) in the switch
      region mediate class switch recombination, and contribute to gene conversion and
      somatic hypermutation in the variable regions. However, the relative extent to
      which AID induces DSB in these regions or between these and other actively
      expressed sequences is unknown. Here, we exploited an enhancer-trap plasmid that
      identifies DSB in actively expressed loci to investigate the frequency and
      position of AID-induced vector integration events in mouse hybridoma cells.
      Compared to control cells, wild-type AID stimulates plasmid integration into the
      genome by as much as 29-fold. Southern and digestion-circularization PCR analysis
      revealed non-uniformity in the integration sites, with biases of 30- and 116-fold
      for the immunoglobulin kappa light chain and mu heavy chain genes, respectively.
      Further, within the immunoglobulin mu gene, 73% of vector integrations map to the
      mu switch region, an enhancement of five- and 12-fold compared to the adjacent
      heavy chain variable and mu gene constant regions, respectively. Thus, among
      potential highly transcribed genes in mouse hybridoma cells, the immunoglobulin
      heavy and light chain genes are important AID targets, with the immunoglobulin mu
      switch region being preferred compared to other genomic sites.

PMID- 18034428
TI  - Toll-like receptors' two-edged sword: when immunity meets apoptosis.
AB  - Toll-like receptors (TLR) have emerged as key players in the detection of
      pathogens and the induction of anti-microbial immune response. TLR recognize
      pathogen-associated molecular patterns, and trigger anti-microbial innate immune
      responses ranging from the secretion of pro-inflammatory mediators to the
      increase of natural killer cell cytotoxicity. Besides activating the innate
      immune response, TLR engagement also shapes the adaptive immune response. Indeed,
      the broad diversity of signaling pathways initiated by TLR is progressively
      unraveled. Recent reports suggested that among the anti-microbial defenses they
      initiate, members of the TLR family can induce apoptosis. This review focuses on
      this newly described function of TLR, and emphasizes the similarities and
      differences between the different apoptosis-signaling pathways described
      downstream of TLR. The functional relevance of TLR-triggered apoptosis is also
      discussed, as therapeutic applications are likely to ensue in the near future.

PMID- 18034429
TI  - Anti-chromatin antibodies drive in vivo antigen-specific activation and somatic
      hypermutation of rheumatoid factor B cells at extrafollicular sites.
AB  - A dominant type of spontaneous autoreactive B cell activation in murine lupus is
      the extrafollicular generation of plasmablasts. The factors governing such
      activation have been difficult to identify due to the stochastic onset and
      chronic nature of the response. Thus, the ability to induce a similar
      autoreactive B cell response with a known autoantigen in vivo would be a powerful
      tool in deciphering how autoimmune responses are initiated. We report here the
      establishment and characterization of a system to initiate autoreactive
      extrafollicular B cell responses, using IgG anti-chromatin antibodies, that
      closely mirrors the spontaneous response. We demonstrate that exogenously
      administered anti-chromatin antibody, presumably by forming immune complexes with
      released nuclear material, drives activation of rheumatoid factor B cells in AM14
      Tg mice. Anti-chromatin elicits autoreactive B cell activation and development
      into antibody-forming cells at the T zone/red pulp border. Plasmablast generation
      occurs equally in BALB/c, MRL/+ and MRL/lpr mice, indicating that an autoimmune
      prone genetic background is not required for the induced response. Importantly,
      infused IgG anti-chromatin induces somatic hypermutation in the absence of a GC
      response, thus proving the extrafollicular somatic hypermutation pathway. This
      system provides a window on the initiation of an autoantibody response and
      reveals authentic initiators of it.

PMID- 18034430
TI  - IFN-beta protects from vascular leakage via up-regulation of CD73.
AB  - Changes in endothelial permeability are crucial in the pathogenesis of many
      diseases. Adenosine is one of the endogenous mediators controlling endothelial
      permeability under normal conditions, and an endothelial cell surface enzyme CD73
      is a key regulator of adenosine production. Here we report that IFN-beta is a
      novel inducer of CD73. We found that pretreatment with IFN-beta dramatically
      improved the vascular barrier function in lungs after intestinal ischemia
      reperfusion injury in wild-type animals in vivo. IFN-beta had absolutely no
      protective effects in CD73-deficient mice, which suffered from more severe lung
      damage than wild-type mice, showing that IFN-beta functions strictly in a CD73
      dependent manner. Most importantly, IFN-beta treatment initiated after the
      ischemic period almost completely inhibited vascular leakage during the
      reperfusion. IFN-beta also induced the expression and activity of CD73 and
      concurrently decreased vascular permeability in cultured human pulmonary
      endothelial cells. These data show that induction of CD73 and improvement of
      vascular barrier are new mechanisms for the anti-inflammatory action of IFN-beta.
      Moreover, IFN-beta treatment may be useful in alleviating vascular leakage
      induced by ischemia-reperfusion injury.

PMID- 18034431
TI  - Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to
      reduction of autoantibody production and amelioration of disease symptoms.
AB  - The presence of autoantibodies specific for nucleic acid-associated antigens is
      the hallmark of systemic lupus erythematosus (SLE). We have recently developed a
      specific inhibitor of TLR7 and TLR9, called immunoregulatory sequence (IRS) 954,
      and showed that it inhibits the induction of IFN-alpha by human plasmacytoid
      dendritic cells in response to DNA and RNA viruses and isolated immune complexes
      from lupus patients. In this study, we show that IRS 954 can prevent progression
      of disease when injected in the lupus prone (NZBxNZW)F1 mice. Following
      treatment, we observed a significant reduction of serum levels of nucleic acid
      specific autoantibodies as well as decreased proteinuria, reduced
      glomerulonephritis, end-organ damage and increased survival. These data
      demonstrate that in addition to its ability to block IFN-alpha, IRS 954 can
      reduce symptoms in a lupus model and thus represents a promising therapeutic
      agent for the treatment of SLE.

PMID- 18034432
TI  - Diseases of protein aggregation and the hunt for potential pharmacological
      agents.
AB  - Protein aggregation is a ubiquitous phenomenon significant to all aspects of
      science. Notably, the formation of protein aggregates is frequently encountered
      in biochemical research and biopharmaceutical industry. Formation of protein
      aggregates is generally regarded to be associated with partially folded
      intermediate species that are susceptible to self-association due to the exposure
      of hydrophobic core. Evidence supports the concept that the formation of
      aggregates in vitro is a generic property of proteins. In human etiology, more
      than 20 different devastating human diseases have been reported to be associated
      with protein aggregation. Although protein aggregation diseases have been the
      center of intense research, much remains to be learned regarding the underlying
      molecular mechanisms. In this review, the general background information on
      protein aggregation is first provided. Next, we summarize the properties,
      characteristics and causes of protein aggregates. Finally, from the perspectives
      of epidemiology, pathogenesis, existing mechanisms, relevant hypotheses, and
      current as well as potential therapeutic approaches, two examples of protein
      aggregation diseases, Alzheimer's disease and cataract, are briefly discussed.
      Importantly, while a variety of molecules have been suggested, the effective
      therapeutic drugs for curing the diseases involving protein aggregation have yet
      to be identified. We believe that a better understanding of the mechanisms of
      protein aggregation process and an extensive investigation into the drug
      penetration, efficacy, and side effects will certainly aid in developing the
      successful pharmacological agents for these diseases.

PMID- 18034433
TI  - Performance evaluation of a silk protein-based matrix for the enzymatic
      conversion of tyrosine to L-DOPA.
AB  - L-DOPA (3,4-dihydroxyphenyl-L-alanine), one of the most important intermediates
      in the melanin biosynthesis pathway, is used for the treatment of Parkinson's
      disease. With a view of developing a cheaper and more effective method for the
      bioconversion of tyrosine to L-DOPA, the potential and performance of a novel
      fibrous matrix prepared from Bombyx mori silk protein fibroin were evaluated for
      the immobilization of tyrosinase. Cross-linkage between fibroin and tyrosinase
      using glutaraldehyde was evident from Fourier transform infra red spectroscopy.
      Maximum product formation occurred when 1000 U enzyme was immobilized on 20 mg
      fibroin. The optimum conditions for maximal L-DOPA production using immobilized
      tyrosinase were 40 degrees C and pH 5.5, conditions that caused a 50% loss of
      free enzyme activity. Immobilized tyrosinase also showed to have a higher degree
      of stability during storage and it retained 80% of its original activity after
      repeated reuses. The efficiency of this immobilized tyrosinase system to produce
      L-DOPA was high, as evident from a high effectiveness factor, between 0.7 and
      0.8, thereby making this method feasible for the large-scale production of L
      DOPA.

PMID- 18034434
TI  - Airborne particle monitoring in clean room environments for stem cell cultures.
AB  - Modern high-technology industrial practices like pharmaceutical and stem cell
      line production demand high-quality environmental conditions to avoid particle
      contamination in the final product. Particles are important because their
      presence can affect both the output and the productivity and because they can
      have repercussion on human health. In this kind of production practice it is
      necessary to implement optimal methods for particle management and to introduce
      an environmental monitoring program. This should also address the regional
      regulatory requirements and will depend on local conditions in each processing
      center. Each center must evaluate its specific needs and establish appropriate
      monitoring procedures.

PMID- 18034435
TI  - Expression and characterization of the acidic subunit from 11S Amaranth seed
      protein.
AB  - Amarantin acidic subunit has the potential to be employed as a functional and a
      nutraceutical protein. To evaluate both possibilities this protein was produced
      in recombinant Escherichia coli Origami (DE3) harboring the expression plasmid
      pET-AC6His. Three different expression factors were assayed: inductor
      concentration, temperature and time of the amarantin acidic subunit accumulation.
      The results indicated that a 0.3 mmol/L concentration of isopropyl-beta-D
      thiogalactoside, at 37 degrees C and 6 h after induction were favorable for high
      expression of amarantin acidic subunit, mostly in the form of inclusion bodies.
      The protein was purified from soluble fraction by immobilized metal affinity
      chromatography, up to 30 mg amarantin acidic subunit/L Terrific broth culture
      were obtained. Sucrose density gradient ultracentrifugation analysis of the
      expressed soluble amarantin acidic subunit revealed that it was assembled in
      monomers. The expression of the amarantin acidic subunit, together with the one
      step purification will facilitate further investigation of this storage protein
      through site-directed mutagenesis.

PMID- 18034436
TI  - Preliminary dielectric measurement and analysis protocol for determining the
      melting temperature and binding energy of short sequences of DNA in solution.
AB  - Measurement of the real dielectric constant of bulk buffer solutions containing
      short sequences of DNA as a function of temperature through the DNA melting or
      denaturiztion transition can be used to determine melting temperatures, T(m), and
      to estimate the binding energy of the complimentary strands. We describe a
      preliminary dielectric measurement and analysis protocol to determine these
      parameters and its application to two known short sequences. The relative real
      dielectric constant for the bulk solutions was determined over the frequency
      range of 50 Hz-20 kHz and temperature range of <40-65 degrees C. The measurements
      were performed on dilute solutions and utilized low electric field strengths.
      Based on fits to the data by modified sigmoid functions, the melting
      temperatures, width of transition, and binding energy for the two sequences in
      solution were estimated. It was observed that the order of the transition
      appeared to be second order. The results were then compared against predictions
      of a number of models from the literature that provide theoretical estimates for
      the melting temperatures of known short sequences of DNA.

PMID- 18034437
TI  - Certification to ensure sustainable production of biofuels.

PMID- 18034438
TI  - Technical aspects of biocatalysis in non-CO2-based supercritical fluids.
AB  - The number of biotransformation processes is increasing rapidly. Part of this
      success is based on the inherent properties of enzymes as chemo-, regio-, and
      enantioselective catalysts. Supercritical fluids (scF) are superior solvents
      inheriting adjustable and partly unique physical properties. These can be
      advantageously combined with biotransformations, as solvent power responds to
      pressure and temperature changes according to the reaction requirements. Among
      the scF, supercritical carbon dioxide has undoubtedly gained the highest
      attention. However, other scF are also recognized to enlarge the possibilities.
      Among these CH(4), C(2)H(6), C(2)H(4), C(3)H(8), CHF(3), and SF(6) are used as
      scF for biocatalysis. This review focuses on the use of non-CO(2) based scF for
      biotransformations. Wherever possible, special emphasis is given on the
      industrial viability of different biocatalytic processes.

PMID- 18034439
TI  - Alkylzinc carboxylates as efficient precursors for zinc oxocarboxylates and
      sulfidocarboxylates.

PMID- 18034440
TI  - Versatile preparation of fluorescent particles based on polyphosphazenes: from
      micro- to nanoscale.
AB  - A series of intrinsically fluorescent hydrophobic and amphiphilic
      polyphosphazenes with ethyl tryptophan (EtTrp) and poly(N-isopropylacrylamide)
      (PNIPAAm) or poly(ethylene glycol) (PEG) as hydrophobic and hydrophilic segments,
      respectively, are synthesized. Depending on polymer composition and preparation
      procedure, particles with diameters ranging from micro- to nanoscale can be
      prepared successfully, which might be used as a visible tracer, both in vitro or
      in vivo, in drug- or gene-delivery systems, as well as in other biomedical
      studies such as diagnostic medicine and brain research. Most importantly, in
      combination with the flexible synthesis and versatile modification of
      polyphosphazene, this method provides a general protocol to engineer a broad
      range of fluorescent particles with different properties based on diverse
      polymers.

PMID- 18034441
TI  - Rhodium-catalyzed allylation of aldehydes with homoallylic alcohols by
      retroallylation and isomerization to saturated ketones with conventional or
      microwave heating.
AB  - The treatment of an aldehyde with a tertiary homoallylic alcohol at 100-250
      degrees C in the presence of cesium carbonate and a rhodium catalyst leads to
      allyl transfer from the homoallylic alcohol to the aldehyde. The process includes
      Rh-mediated retroallylation to form an allyl rhodium species as the key
      intermediate. The homoallylic alcohol formed initially through allyl transfer is
      converted under the reaction conditions into the corresponding saturated ketone
      when bulky ligands are used. Microwave heating at 250 degrees C accelerates the
      reaction significantly.

PMID- 18034442
TI  - A series of isolable silanoic thio-, seleno-, and telluroesters (LSi(=X)OR) with
      donor-supported Si=X double bonds (L = beta-diketiminate; X = S, Se, Te).
AB  - The first silicon analogues of carbonic (carboxylic) esters, the silanoic thio-,
      seleno-, and tellurosilylesters 3 (Si=S), 4 (Si=Se), and 5 (Si=Te), were prepared
      and isolated in crystalline form in high yield. These thermally robust compounds
      are easily accessible by direct reaction of the stable siloxysilylene
      L(Si:)OSi(H)L' 2 (L = HC(CMe)2[N(aryl)2], L' = CH[(C=CH2)-CMe][N(aryl)]2; aryl =
      2,6-iPr2C6H3) with the respective elemental chalcogen. The novel compounds were
      fully characterized by methods including multinuclear NMR spectroscopy and single
      crystal X-ray diffraction analysis. Owing to intramolecular N-->Si donor-acceptor
      support of the Si=X moieties (X=S, Se, Te), these compounds have a classical
      valence-bond N(+)-Si-X(-) resonance betaine structure. At the same time, they
      also display a relatively strong nonclassical Si=X pi-bonding interaction between
      the chalcogen lone-pair electrons (n(pi) donor orbitals) and two antibonding Si-N
      orbitals (sigma*(pi) acceptor orbitals mainly located at silicon), which was
      shown by IR and UV/Vis spectroscopy. Accordingly, the Si=X bonds in the
      chalcogenoesters are 7.4 (3), 6.7 (4), and 6.9 % (5) shorter than the
      corresponding Si-X single bonds and, thus, only a little longer than those in
      electronically less disturbed Si=X systems ("heavier" ketones).

PMID- 18034443
TI  - Silylmetalation of alkenes.
AB  - Silylmetalation of alkenes is challenging due to the low reactivity of the
      substrates. In contrast, carbometalation of alkenes has been realized through
      several innovative methods, including activation of the reagent and the
      substrate. A similar approach could be applicable to silylmetalation of alkenes,
      and we have recently developed a bimetal activation method using zincate
      complexes for this purpose. Here, we describe how the silylzincation of alkenes
      was achieved. First, the strategies for carbometalation of alkenes will be
      summarized. Secondly, the history and development of silylzincation chemistry are
      briefly described. Then the details of our findings related to two types of
      silylzincation of alkenes, as well as recent progress in mechanistic studies, are
      discussed. The key point in the silylzincation of alkenes proved to be the
      bimetal activation of the substrate. One metal (copper or titanium) strongly
      coordinates and activates the alkene moiety, and the other metal (zinc) acts as
      the electron acceptor from the silyl group by way of the alkene moiety. This dual
      activation concept is expected to be applicable to other combinations of metals,
      as well as to new types of reactions.

PMID- 18034445
TI  - Assessable consequences of through-bond donor-acceptor interactions in beta
      aminoketones.
AB  - Reported are the syntheses of ester-functionalized (6-8) and alkyl-substituted
      (9) 1-aza-adamantanones; the easy handling of the compounds provides an
      opportunity to comprehensively study the fundamental changes in structure and
      reactivity that can accompany the donor-acceptor arrangement in rigid beta
      aminoketones. X-ray structural analysis of trione 6 and dione 7 reveals bond
      length and angle variations consistent with through-bond (hyperconjugative) donor
      acceptor interactions. Observed is a shortening of the C-N bond, elongation of
      the central C-C bond (to approximately 1.6 A), and a significant pyramidalization
      of the carbonyl carbon within the donor-sigma-acceptor pathway. UV/Vis spectra of
      6-9 show a new absorption maximum (lambda(max)=260-275 nm in three solvents), the
      so-called "sigma-coupled transition"; the molar absorptivity scales with the
      number of carbonyl groups (for trione 6, epsilon approximately 3000, for dione 7,
      epsilon approximately 2000) and the band reversibly disappears upon addition of
      acid. IR and (13)C NMR spectroscopic data show trends consistent with through
      bond donation to the carbonyl acceptor groups and commensurate weakening of the
      carbonyl pi bond. High yielding acid-mediated fragmentations are used to
      illustrate the effects of the donor-acceptor arrangement on the reactivity of the
      molecules. Given that donor-sigma-acceptor molecules have recently been found to
      show self-assembly behavior and macromolecular properties linked to their unusual
      structure, the current analysis encourages further consideration of the systems
      in advanced materials applications.

PMID- 18034444
TI  - Rhodium-complex-catalyzed asymmetric hydrogenation: transformation of
      precatalysts into active species.
AB  - The use of diolefin-containing rhodium precatalysts leads to induction periods in
      asymmetric hydrogenation of prochiral olefins. Consequently, the reaction rate
      increases in the beginning. The induction period is caused by the fact that some
      of the catalyst is blocked by the diolefin and thus not available for
      hydrogenation of the prochiral olefin. Therefore, the maximum reaction rate
      cannot be reached initially. Due to the relatively slow hydrogenation of
      cyclooctadiene (cod) the share of active catalysts increases at first, and this
      leads to typical induction periods. The aim of this work is to quantify the
      hydrogenation of the diolefins cyclooctadiene (cod) and norborna-2,5-diene (nbd)
      for cationic complexes of the type [Rh(ligand)(diolefin)]BF(4) for the ligands
      Binap (1,1'-binaphthalene-2,2'-diylbis(phenylphosphine)), Me-Duphos (1,2-bis(2,5
      dimethylphospholano)benzene, and Catasium in the solvents methanol, THF, and
      propylene carbonate. Furthermore, an approach is presented to determine the
      desired rate constant and the resulting respective pre-hydrogenation time from
      stoichiometric hydrogenations of the diolefin complexes via UV/Vis spectroscopy.
      This method is especially useful for very slow diolefin hydrogenations (e.g., cod
      hydrogenation with the ligands Me-Duphos, Et-Duphos (1,2-bis(2,5
      diethylphospholano)benzene), and dppe (1,2-bis(diphenylphosphino)ethane).

PMID- 18034446
TI  - Alkyne versus allene activation in platinum- and gold-catalyzed
      cycloisomerization of hydroxylated 1,5-allenynes.
AB  - Chemo- and stereoselective transformations of 3-hydroxy-1,5-allenynes 1 into a
      variety of new and potentially useful cyclic compounds have been achieved.
      Substrates bearing a silyl group at the alkyne moiety undergo purely thermal or
      Lewis acid catalyzed Alder-ene type transformations into 2-methylene-3
      vinylcyclopent-3-enol derivatives 2. When heated in the presence of a catalytic
      amount of PtCl(2) or PtCl(4), these incipient cyclopentenols could be further
      transformed into 3-vinylcyclopent-2-enones 3. On the other hand, alkyl
      substituted 3-hydroxy-1,5-allenynes proved to be stable under refluxing
      conditions. Nevertheless, PtCl(2) and PtCl(4) could selectively activate the
      alkyne moiety of these substrates toward intramolecular nucleophilic attack of
      the internal allene double bond to yield unprecedented 6
      methylenebicyclo[3.1.0]hexan-3-one derivatives 4. With gold-based catalysts,
      provided that the reaction is carried out in dichloromethane, both Au(I) and
      Au(III) complexes selectively activate the allene fragment of the substrates
      toward intramolecular nucleophilic attack of the hydroxyl group to yield 2
      ethynyl-3,6-dihydro-2H-pyrans 5. Compounds of type 4 can also be formed with
      Au(I) and Au(III) complexes if the reaction is carried out in toluene. The
      reactivity of these new compounds has been partially investigated, and polycyclic
      ketones were obtained after oxidation under mild conditions or gold-catalyzed
      cycloisomerization.

PMID- 18034447
TI  - Use of evidence in economic decision models: practical issues and methodological
      challenges.
AB  - This paper outlines the current 'state of play' regarding the use of evidence in
      decision modelling and highlights both practical issues and methodological
      challenges related to identifying, combining and reporting evidence to inform
      decision model parameters and structure. Based on discussions at two MRC HSRC
      funded workshops consisting of 37 experts from a range of disciplines (i.e.
      decision-makers, health economists, information specialists, operations
      researchers and statisticians), it aims to derive a multi-disciplinary standpoint
      on the appropriate use of evidence in economic decision models and, where
      applicable, offer some suggestions for good modelling practice. Gaps in the
      established methodology knowledge base are identified for future research.

PMID- 18034452
TI  - HER2 targeted polyplexes: the effect of polyplex composition and conjugation
      chemistry on in vitro and in vivo characteristics.
AB  - Knowledge of the influence of targeting ligands on pharmacokinetics and
      biodistribution of polymeric nonviral vectors is presently limited. We
      investigated the properties of three structurally different conjugates of
      polyethylenglycol-modified polyethylenimine coupled to the HER2 specific antibody
      Trastuzumab. Unlike polyethylenimine, conjugates formed small (100-230 nm) DNA
      polyplexes with zeta-potentials of +/- 2 mV at a broad range of N/P ratios.
      Stability as assessed by heparin displacement was slightly improved compared to
      unmodified copolymers. Erythrocyte aggregation and hemolysis were strongly
      reduced with conjugates. Conjugate polyplexes showed significant differences in
      specificity and transfection efficiency in vitro. These could be attributed to
      differences in cell binding and uptake assessed by flow cytometry.
      Pharmacokinetics of conjugates in mice revealed significant improvements over
      free plasmid DNA and polyethylenimine. Area under the plasma level-time curve of
      conjugates was increased up to 48% or 114% compared to that of polyethylenimine
      or free plasmid DNA, respectively. Deposition of conjugate polyplexes in lung and
      spleen was significantly reduced compared to that of polyethylenimine.
      Differences could be attributed to antibody conjugation since no significant
      differences in pharmacokinetics and biodistribution were found between
      conjugates. These findings demonstrate that conjugated antibodies not only confer
      active targeting but also significantly improve in vivo properties of polyplexes.

PMID- 18034453
TI  - Accurate annotation of peptide modifications through unrestrictive database
      search.
AB  - Proteins are extensively modified after translation due to cellular regulation,
      signal transduction, or chemical damage. Peptide tandem mass spectrometry can
      discover post-translational modifications, as well as sequence polymorphisms.
      Recent efforts have studied modifications at the proteomic scale. In this
      context, it becomes crucial to assess the accuracy of modification discovery. We
      discuss methods to quantify the false discovery rate from a search and
      demonstrate how several features can be used to distinguish valid modifications
      from search artifacts. We present a tool, PTMFinder, which implements these
      methods. We summarize the corpus of post-translational modifications identified
      on large data sets. Thousands of known and novel modification sites are
      identified, including site-specific modifications conserved over vast
      evolutionary distances.

PMID- 18034454
TI  - In silico tools for predicting peptides binding to HLA-class II molecules: more
      confusion than conclusion.
AB  - Identification of promiscuous peptides, which bind to human leukocyte antigen, is
      indispensable for global vaccination. However, the development of such vaccines
      is impaired due to the exhaustive polymorphism in human leukocyte antigens. The
      use of in silico tools for mining such peptides circumvents the expensive and
      laborious experimental screening methods. Nevertheless, the intrepid use of such
      tools warrants a rational assessment with respect to experimental findings. Here,
      we have adopted a 'bottom up' approach, where we have used experimental data to
      assess the reliability of existing in silico methods. We have used a data set of
      179 peptides from diverse antigens and have validated six commonly used in silico
      methods; ProPred, MHC2PRED, RANKPEP, SVMHC, MHCPred, and MHC-BPS. We observe that
      the prediction efficiency of the programs is not balanced for all the HLA-DR
      alleles and there is extremely high level of discrepancy in the prediction
      efficiency apropos of the nature of the antigen. It has not escaped our notice
      that the in silico methods studied here are not very proficient in identifying
      promiscuous peptides. This puts a much constraint on the intrepid use of such
      programs for human leukocyte antigen class II binding peptides. We conclude from
      this study that the in silico methods cannot be wholly relied for selecting
      crucial peptides for development of vaccines.

PMID- 18034455
TI  - Large-scale identification and evolution indexing of tyrosine phosphorylation
      sites from murine brain.
AB  - Metazoans employ reversible tyrosine phosphorylation to regulate innumerable
      biological processes. Thus, the large-scale identification of tyrosine
      phosphorylation sites from primary tissues is an essential step toward a
      molecular systems understanding of dynamic regulation in vivo. The relative
      paucity of phosphotyrosine has greatly limited its identification in large-scale
      phosphoproteomic experiments. However, using antiphosphotyrosine peptide
      immunoprecipitations, we report the largest study to date of tyrosine
      phosphorylation sites from primary tissue, identifying 414 unique tyrosine
      phosphorylation sites from murine brain. To measure the conservation of
      phosphorylated tyrosines and their surrounding residues, we constructed a
      computational pipeline and identified patterns of conservation within the
      signature of phosphotyrosine.

PMID- 18034456
TI  - Highly robust, automated, and sensitive online TiO2-based phosphoproteomics
      applied to study endogenous phosphorylation in Drosophila melanogaster.
AB  - Reversible protein phosphorylation ranks among the most important post
      translational modifications, and elucidation of phosphorylation sites is
      essential to understand the regulation of key cellular processes such as signal
      transduction. Enrichment of phosphorylated peptides is a prerequisite for
      successful analysis due to their low stoichiometry, heterogeneity, and low
      abundance. Enrichment is often performed manually, which is inherently labor
      intensive and a major hindrance in large-scale analyses. Automation of the
      enrichment method would vastly improve reproducibility and thereby facilitate
      'high-throughput' phosphoproteomics research. Here, we describe a robust and
      automated online TiO 2-based two-dimensional chromatographic approach to
      selectively enrich phosphorylated peptides from digests of complete cellular
      lysates. We demonstrate method enhancement for both adsorption and desorption of
      phosphorylated peptides resulting in lower limits of detection. Phosphorylated
      peptides from a mere 500 attomole tryptic digest of a protein mixture were easily
      detected. With the combination of strong cation exchange chromatography with the
      online TiO 2 enrichment, 2152 phosphopeptides were enriched from 250 microg of
      protein originating for the cell lysate of Drosophila melanogaster S2 cells. This
      is a 4-fold improvement when compared to an enrichment strategy based solely on
      strong cation exchange/LC-MS. Phosphopeptide enrichment methods are intrinsically
      biased against relatively basic phosphopeptides. Analysis of the p I
      distributions of the enriched/detected phosphopeptides showed that the p I
      profile resembles that of a total Drosophila protein digest, revealing that the
      current described online procedure does not discriminate against either more
      acidic or basic phosphopeptides. However, careful comparison of our new and
      existing phosphopeptide enrichment techniques also reveal that, like many
      enrichment techniques, we are still far from comprehensive phosphoproteomics
      analyses, and we describe several factors that still require to be addressed.
      Still, as the online approach allows the complementary measurements of
      phosphopeptides and their nonphosphorylated counterparts in subsequent analyses,
      this method is well-suited for automated quantitative phosphoproteomics.

PMID- 18034458
TI  - Compound K enhances insulin secretion with beneficial metabolic effects in db/db
      mice.
AB  - Compound K (CK) is a final metabolite of panaxadiol ginsenosides. Although Panax
      ginseng is known to have antidiabetic activity, the active ingredient is not yet
      fully identified. In our preliminary studies, panaxadiol ginsenosides showed
      insulin secretion stimulating activity. Therefore, it would be interesting to
      know whether and how CK has antidiabetic activity. In in vitro studies using HIT
      T15 cells and primary cultured islets, CK enhanced the insulin secretion in a
      concentration-dependent manner. This effect, however, was completely abolished in
      the presence of diazoxide (K+ channel opener) or nifedipine (Ca2+ channel
      blocker). Insulin secretion stimulating activity of a single oral CK
      administration was also confirmed with an oral glucose tolerance test (OGTT)
      using ICR mice. From these studies, we may conclude that CK lowered the plasma
      glucose level by stimulating insulin secretion and this action was presumably
      associated with an ATP-sensitive K+ channel. In a long-term study using C57BL/KsJ
      db/ db mice, CK treatment significantly decreased the fasting blood glucose
      levels in a dose-dependent fashion. OGTT revealed that CK improved glucose
      tolerance with increased insulin levels 30 min after the glucose challenge.
      Concurrently, CK treatment prevented the destruction of islets and preserved more
      insulin. Next, to gain insight into the extra-pancreatic molecular mechanism of
      CK, we performed a global gene expression profiling study in the liver and
      adipose tissues. According to DNA microarray analysis, CK shifted glucose
      metabolism from hepatic glucose production to hepatic glucose utilization in the
      liver and improved insulin sensitivity through enhancing plasma adiponectin
      levels, resulting in overexpression of genes for adipogenesis and glucose
      transporter in the adipose tissue. Taken together, we may suggest that CK could
      be developed as a therapeutic tool in type 2 diabetic patients with disability of
      insulin secretion and/or insulin resistance.

PMID- 18034459
TI  - Resistance to oxidation of white wines assessed by voltammetric means.
AB  - This work concerns the development of a methodology suited to measure the
      resistance to oxidation of white wines by cyclic voltammetry. The voltammetric
      responses of several white wines of different origin and age were analyzed in the
      oxidation potential range (0.2-1.2 V vs SCE). Currents measured at fixed
      potentials were correlated to the concentration of ascorbic acid, SO2, and total
      phenolics. A forced degradation study was monitored by cyclic voltammetry; from
      plots of current versus time, the consumption rates of oxidizable species in wine
      were estimated.

PMID- 18034457
TI  - A quantitative proteomic analysis of mitochondrial participation in p19 cell
      neuronal differentiation.
AB  - A quantitative proteomic analysis of changes in protein expression accompanying
      the differentiation of P19 mouse embryonal carcinoma cells into neuron-like cells
      using isobaric tag technology coupled with LC-MS/MS revealed protein changes
      reflecting withdrawal from the cell cycle accompanied by a dynamic reorganization
      of the cytoskeleton and an up-regulation of mitochondrial biogenesis. Further
      study of quantitative changes in abundance of individual proteins in a purified
      mitochondrial fraction showed that most mitochondrial proteins increased
      significantly in abundance. A set of chaperone proteins did not participate in
      this increase, suggesting that neuron-like cells are relatively deficient in
      mitochondrial chaperones. We developed a procedure to account for differences in
      recovery of mitochondrial proteins during purification of organelles from
      distinct cell or tissue sources. Proteomic data supported by RT-PCR analysis
      suggests that enhanced mitochondrial biogenesis during neuronal differentiation
      may reflect a large increase in expression of PGC-1alpha combined with down
      regulation of its negative regulator, p160 Mybbp1a.

PMID- 18034460
TI  - Label-free DNA detection of hepatitis C virus based on modified conducting
      polypyrrole films at microelectrodes and atomic force microscopy tip-integrated
      electrodes.
AB  - We present a new strategy for the label-free electrochemical detection of DNA
      hybridization for detecting hepatitis C virus based on electrostatic modulation
      of the ion-exchange kinetics of a polypyrrole film deposited at microelectrodes.
      Synthetic single-stranded 18-mer HCV genotype-1-specific probe DNA has been
      immobilized at a 2,5-bis(2-thienyl)-N-(3-phosphoryl-n-alkyl)pyrrole film
      established by electropolymerization at the previously formed polypyrrole layer.
      HCV DNA sequences (244-mer) resulting from the reverse transcriptase-linked
      polymerase chain reaction amplification of the original viral RNA were monitored
      by affecting the ion-exchange properties of the polypyrrole film. The performance
      of this miniaturized DNA sensor system was studied in respect to selectivity,
      sensitivity, and reproducibility. The limit of detection was determined at
      1.82x10(-21) mol L(-1). Control experiments were performed with cDNA from HCV
      genotypes 2a/c, 2b, and 3 and did not show any unspecific binding. Additionally,
      the influence of the spacer length of 2,5-bis(2-thienyl)-N-(3-phosphoryl-n
      alkyl)pyrrole on the behavior of the DNA sensor was investigated. This biosensing
      scheme was finally extended to the electrochemical detection of DNA at
      submicrometer-sized DNA biosensors integrated into bifunctional atomic force
      scanning electrochemical microscopy probes. The 18-mer DNA target was again
      monitored by following the ion-exchange properties of the polypyrrole film.
      Control experiments were performed with 12-base pair mismatched sequences.

PMID- 18034461
TI  - Phosphorylation of the beta2-adrenergic receptor in plasma membranes by intrinsic
      GRK5.
AB  - Characterization of the GRKs participating in the phosphorylation of the beta2
      adrenergic receptor (beta2AR) have in part been limited by the lack of a simple
      cell-free assay with membrane-bound beta2AR and GRKs. We describe here a cell
      free assay for GRK phosphorylation of the beta2AR in a postnuclear 600g fraction
      and washed membranes by intrinsic GRK activity using the GRK phosphosite-specific
      antibody that recognizes pS(355,356). Treatment of these cell-free preparations
      with 1.0 microM isoproterenol (ISO) caused a rapid maximal 10-15-fold increase in
      GRK site phosphorylation of the beta2AR (t1/2 = 1 min) with an EC50 for ISO
      stimulation of approximately 80 nM. Extensively washed plasma membrane fractions
      retained the 10-15-fold ISO stimulation of GRK site phosphorylation and GRK5
      levels while being depleted of GRK2 and GRK6. Stimulation of GRK site
      phosphorylation by a range of partial agonists correlated well with their
      intrinsic efficacy for stimulation of adenylyl cyclase. GRK phosphorylation of
      the beta2AR in the washed membrane fraction caused minimal desensitization of ISO
      stimulation of adenylyl cyclase activity. Association of GRK5 with the beta2AR in
      intact cells was demonstrated by a high level of basal BRET2 using beta2AR-Rluc
      and GRK5-GFP2 that was not diminished by agonist stimulation. BRET2 between the
      beta2AR-Rluc and GFP2-betaarrestin 2 was increased by agonist, whereas BRET2
      between the beta2AR and GRK2-GFP2 was not significant. On the basis of the level
      of GRK5-mediated phosphorylation we observe in isolated membrane fractions and co
      localization of the beta2AR and GRK5, we conclude that GRK5 plays a distinctive
      role in the phosphorylation of the beta2AR.

PMID- 18034462
TI  - Mass spectrometric analysis of intact lipooligosaccharide: direct evidence for O
      acetylated sialic acids and discovery of O-linked glycine expressed by
      Campylobacter jejuni.
AB  - The lipooligosaccharides (LOS) of Campylobacter jejuni is an important virulence
      factor. Its core oligosaccharide component is frequently sialylated and bears a
      close resemblance with host gangliosides. The display of ganglioside mimics by
      this bacterium is believed to trigger the onset of the autoimmune condition
      Guillain-Barre syndrome (GBS) in some individuals. Considerable effort has been
      directed toward the structural characterization of the glycan component of the
      LOS of C. jejuni strains isolated from GBS patients. Capillary electrophoresis
      mass spectrometry (CE-MS) has been a particularly useful analytical technique
      applied toward this task. Conventional analysis of bacterial LOS by CE-MS has
      generally involved the prior removal of O-acyl lipid chains, which is necessary
      for the effective solubilization and separation of the heterogeneous ensemble of
      LOS species. Unfortunately, O-deacylation causes the undesired removal of
      important glycan-associated O-linked modifications, such as O-acetate and O
      linked amino acids. In this report, we describe a CE-MS technique developed for
      the rapid analysis of fully intact LOS from C. jejuni. Using this method, we
      report the structural characterization of the glycan from 10 GBS-associated
      strains and two enteritis strains, using material isolated from as little as one
      colony. The application of this technique has enabled us to unambiguously
      identify LOS-bound O-acetylated sialic acid in a number of strains and has
      revealed for the first time that C. jejuni frequently modifies its core with O
      linked glycine. Our studies demonstrate that MS-based structural analysis of
      bacterial LOS can be optimized to the level where only a single-colony quantity
      of material is required and time-consuming chemical treatments can be avoided.

PMID- 18034463
TI  - Dissecting the component reactions catalyzed by the actinorhodin minimal
      polyketide synthase.
AB  - The actinorhodin (act) minimal polyketide synthase (PKS) from Streptomyces
      coelicolor consists of three proteins: an acyl carrier protein (ACP) and two beta
      ketoacyl ACP synthase components known as KSalpha and KSbeta. The act minimal PKS
      catalyzes at least 18 separate reactions which can be divided into loading,
      initiation, extension, and cyclization and release phases. Two quantitative
      kinetic assays were developed and used to measure individual rate and Michaelis
      constants for loading, initiation and extension steps. In the minimal PKS, the
      reaction between malonyl CoA and ACP to form malonyl ACP (loading) is the rate
      limiting step (kcat = 0.49 min-1, KM = 207 microM). This reaction increases 5
      fold in rate in the presence of KSalphaKSbeta (kcat = 2.3 min-1, KM = 215
      microM). In the presence of S. coelicolor malonyl CoA:ACP transacylase (MCAT),
      the rate of loading increases and the kinetic parameters of malonyl-ACP as a
      substrate of KSalphaKSbeta can be measured (kcat = 20.6 min-1, KM = 2.4 microM).
      Under these conditions, it appears that decarboxylation of malonyl-ACP to form
      acetyl-ACP (initiation) is the rate-limiting step. When an excess of acetyl ACP
      is supplied, either chain extension, cyclization, or release steps become rate
      limiting (k approximately 60 min-1). No ACP-bound intermediates could be
      observed, suggesting that partially or fully extended chains do not accumulate
      because chain extension is rate limiting under these conditions and that
      cyclization and release are fast. apo-ACP acts as a mixed inhibitor of malonyl
      ACP binding to KSalpha/KSbeta (Kic = 50 microM, Kiu = 137 microM), but apo-ACP
      does not appear to inhibit MCAT.

PMID- 18034464
TI  - Ab initio study of low-lying electronic states of SnCl2+.
AB  - Complete active space self-consistent field (CASSCF), multireference
      configuration interaction (MRCI), and restricted-spin coupled-cluster singles
      doubles with perturbative triples [RCCSD(T)] calculations have been carried out
      on low-lying doublet and quartet states of SnCl2+, employing basis sets of up to
      aug-cc-pV5Z quality. Effects of core correlation and off-diagonal spin-orbit
      interaction on computed vertical ionization energies were investigated. The best
      theoretical estimate of the adiabatic ionization energy (including zero-point
      vibrational energy correction) to the X2A1 state of SnCl2+ is 10.093+/-0.010 eV.
      The first photoelectron band of SnCl2 has also been simulated by employing
      RCCSD(T)/aug-cc-pV5Z potential energy functions and including Duschinsky rotation
      and anharmonicity.

PMID- 18034465
TI  - Dynamics of ultrafast intramolecular charge transfer with 1-tert-butyl-6-cyano
      1,2,3,4-tetrahydroquinoline (NTC6) in n-hexane and acetonitrile.
AB  - The intramolecular charge transfer (ICT) reaction of 1-tert-butyl-6-cyano-1,2,3,4
      tetrahydroquinoline (NTC6) in n-hexane and acetonitrile (MeCN) is investigated by
      picosecond fluorescence experiments as a function of temperature and by
      femtosecond transient absorption measurements at room temperature. NTC6 in n
      hexane is dual fluorescent from a locally excited (LE) and an ICT state, with a
      quantum yield ratio Phi'(ICT)/Phi(LE) of 0.35 at +25 degrees C and 0.67 at -95
      degrees C, whereas in MeCN mainly an ICT emission is observed. From the
      temperature dependence of Phi'(ICT)/Phi(LE) for NTC6 in n-hexane, an LE/ICT
      enthalpy difference DeltaH of -2.4 kJ/mol is determined. For comparison, 1
      isopropyl-6-cyano-1,2,3,4-tetrahydroquinoline (NIC6) is also investigated. This
      molecule does not undergo an ICT reaction, because of its larger energy gap
      DeltaE(S1,S2). From the molar absorption coefficient epsilonmax of NTC6 as
      compared with other aminobenzonitriles, a ground-state amino twist angle theta of
      approximately 22 degrees is deduced. The increase of epsilonmax between n-hexane
      and MeCN indicates that theta decreases when the solvent polarity becomes larger.
      Whereas single-exponential LE fluorescence decays are obtained for NIC6 in n
      hexane and MeCN, the LE and ICT decays of NTC6 in these solvents are double
      exponential. For NTC6 in n-hexane at -95 degrees C, with a shortest decay time of
      20 ps, the forward (ka=2.5x10(10) s(-1)) and backward (kd=2.7x10(10) s(-1)) rate
      constants for the LE<-->ICT reaction are determined from the time-resolved LE and
      ICT fluorescence spectra. For NTC6 in n-hexane and MeCN, the excited-state
      absorption (ESA) spectrum at 200 fs after excitation is similar to the LE(ESA)
      spectra of NIC6 and 4-(dimethylamino)benzonitrile (DMABN), showing that LE is the
      initially excited state for NTC6. These results indicate that the LE states of
      NTC6, NIC6, and DMABN have a comparable molecular structure. The ICT(ESA)
      spectrum of NTC6 in n-hexane and MeCN resembles that of DMABN in MeCN, likewise
      indicating a similar ICT structure for NTC6 and DMABN. From the decay of the LE
      absorption and the corresponding growing-in for the ICT state of NTC6, it is
      concluded that the ICT state originates from the LE precursor and is not formed
      by direct excitation from S0, nor via an S2/ICT conical intersection. The same
      conclusion was made from the time-resolved (picosecond) fluorescence spectra,
      where there is no ICT emission at time zero. The decay of the LE(ESA) band of
      NTC6 in n-hexane occurs with a shortest time tau2 of 2.2 ps. The ICT reaction is
      much faster (tau2 = 0.82 ps) in the strongly polar MeCN. The absence of
      excitation wavelength dependence (290 and 266 nm) for the ESA spectra in MeCN
      also shows that LE is the ICT precursor. With NIC6 in n-hexane and MeCN, a decay
      or growing-in of the femtosecond ESA spectra is not observed, in line with the
      absence of an ICT reaction involving an S2/ICT conical intersection.

PMID- 18034466
TI  - Bonding analyses, formation energies, and vibrational properties of M-R2dtc
      complexes (M=Ag(I), Ni(II), Cu(II), or Zn(II)).
AB  - Detailed theoretical studies based on density functional theory (DFT)/B3LYP
      calculations of dimethyl- and diethyldithiocarbamate complexes of Ni(II), Cu(II),
      Zn(II), and Ag(I) are performed to characterize the metal-ligand bonding type as
      well as the metal-ligand bonding strength depending on the metal and the dialkyl
      substituent. The metal-ligand interactions in the studied complexes are
      investigated by means of charge decomposition analysis, energy partitioning
      analysis (EPA), and natural bond orbital analysis. According to the EPA
      calculations, the electrostatic attraction is the dominant contribution to the M
      S2(R2dtc) (dtc=dithiocarbamate) bonding. The electrostatic and the orbital
      energies follow the order of the total binding energy, and hence both
      contributions are responsible for the binding energy order of M(R2dtc)2
      complexes. The stability of the M(R2dtc)2 complexes is estimated by means of
      calculated formation reaction energies in the gas phase and solution, and it
      decreases in the order Ni(R2dtc)2>Cu(R2dtc)2>Zn(R2dtc)2. Larger formation
      reaction energies are found for M(Et2dtc)2 than for M(Me2dtc)2 complexes. The
      calculations predict stabilization of M(II)(R2dtc)2 complexes going from the gas
      phase to a polar solvent and destabilization of the bidentate AgR2dtc complex in
      a polar solvent. Gas-phase frequency calculations of all possible bonding types,
      symmetrical, asymmetrical, and uni- and bidentate, predict one band due to the
      nu(CS) IR absorption, and therefore the number of the bands in the 1060-920 cm(
      1) region could not be used to discern the metal-ligand bonding type. Periodic
      DFT frequency calculations for Cu(Et2dtc)2 reveal that the splitting observed in
      the solid-state spectra of the complexes arises from the nonplanar MS4 fragment
      and intermolecular contacts but not from asymmetrical bonding. The calculations
      suggest that the important vibrational characteristic that can be used to discern
      uni- and bidentate bonding is the Raman activity of the nu(CS) band: It is very
      high for the unidentate dtc bonding (nu(C=S)) and low for the bidentate bonding
      (nuas(CS)).

PMID- 18034467
TI  - O-H bond dissociation enthalpies of oximes: a theoretical assessment and
      experimental implications.
AB  - By using a multilayer composite ab initio method ONION-G3B3, we calculated O-H
      bond dissociation enthalpies (BDEs) of 58 oximes that were measured
      experimentally. Experimental BDEs derived from thermal decomposition kinetics and
      calorimetric measurements were found to be consistent with the theory. However,
      the electrochemical method was found to give questionably high BDEs possibly due
      to errors in the measurement of pKa's or redox potentials. Subsequently, the
      performances of a variety of DFT functionals including B3LYP, B3P86, B3PW91,
      BHandH, BHandHLYP, BMK, PBE1PBE, MPW1KCIS, mPWPW91, MPW1B95, and MPW1K were
      tested to calculate oxime O-H BDEs, where ROBHandHLYP was found to be the most
      accurate. By using this method, we calculated O-H BDEs of over 140 oximes in a
      systematic fashion. All of the calculated O-H BDEs fell in the range from 76.8 to
      89.8 kcal/mol. An amino group on the azomethine carbon was found to strengthen
      the O-H bond, whereas bulky alkyl substituents on oximes decreased O-H BDEs due
      to their large steric-strain-relieving effects in the process of O-H bond
      cleavage. Para substituents had little effect on the BDEs of benzaldoximes and
      phenyl methyl ketoximes. Finally, on the basis of a spin distribution
      calculation, aryl-, alkyl-, and carbonyl-substituted iminoxyl radicals were found
      to be sigma-radicals, whereas amino-substituted iminoxyl radicals were of pi
      structure.

PMID- 18034468
TI  - Natural product-likeness score and its application for prioritization of compound
      libraries.
AB  - Natural products (NPs) have been optimized in a very long natural selection
      process for optimal interactions with biological macromolecules. NPs are
      therefore an excellent source of validated substructures for the design of novel
      bioactive molecules. Various cheminformatics techniques can provide useful help
      in analyzing NPs, and the results of such studies may be used with advantage in
      the drug discovery process. In the present study we describe a method to
      calculate the natural product-likeness score--a Bayesian measure which allows for
      the determination of how molecules are similar to the structural space covered by
      natural products. This score is shown to efficiently separate NPs from synthetic
      molecules in a cross-validation experiment. Possible applications of the NP
      likeness score are discussed and illustrated on several examples including
      virtual screening, prioritization of compound libraries toward NP-likeness, and
      design of building blocks for the synthesis of NP-like libraries.

PMID- 18034469
TI  - Thermal imidization and structural evolution of thin films of poly(4,4'
      oxydiphenylene p-pyromellitamic diethyl ester).
AB  - The evolution of chemical composition and structure during the thermal
      imidization of an ester-type polyimide precursor, poly(4,4'-oxydiphenylene p
      pyromellitamic diethyl ester), in micrometer scale films were studied for a
      heating rate of 2.0 degrees C/min with time-resolved synchrotron X-ray
      diffraction, in-situ infrared spectroscopy, and modulated differential scanning
      calorimetry. Our analyses show that the precursor polymer undergoes imidization
      in a two-step process. In the first step, the precursor polymer is decomplexed
      from the residual solvent molecules, and in the second step, it undergoes imide
      ring formation with the release of ethanol as a byproduct. The imidization
      reaction starts around 210 degrees C and continues up to 320 degrees C. The
      thermal imidization reaction induces the structural evolution of the film. As the
      imidization reaction proceeds, the coherent length along the polymer chain axis
      increases. This imidization-induced structural evolution was found to occur via
      three steps: (i) initiation, (ii) the first crystallization, and (iii) the second
      crystallization. The initiation step is necessary prior to the evolution of the
      crystalline structure to increase the chain mobility of the precursor polymer
      chains, and it requires thermal heating up to at least 238 degrees C at which
      point 22.5% of the imidization is complete. Thereafter, the first crystallization
      occurs up to 310 degrees C, at which point 98.3% of the imidization is complete.
      In the range 310-380 degrees C, the second crystallization occurs and produces
      almost complete imidization of the polymer chains.

PMID- 18034470
TI  - Ab initio optical absorption spectra of size-expanded xDNA base assemblies.
AB  - We present the results of time-dependent density functional theory calculations
      of the optical absorption spectra of synthetic nucleobases and of their hydrogen
      bonded and stacked base pairs. We focus on size-expanded analogues of the natural
      nucleobases obtained through the insertion of a benzene ring bonded to the planar
      heterocycles (x-bases), according to the protocol designed and realized by the
      group of Eric Kool (e.g., see: Gao, J.; Liu, H.; Kool, E.T. Angew. Chem., Int.
      Ed. 2005, 44, 3118, and references therein). We find that the modifications of
      the frontier electron orbitals with respect to natural bases, which are induced
      by the presence of the aromatic ring, also affect the optical response. In
      particular, the absorption onset is pinned by the benzene component of the HOMO
      of each x-base (xA, xG, xT, xC). In addition, the main trait of the H-bonding
      interbase coupling is a conspicuous red shift of spectral peaks in the low-energy
      range. Finally, the hypochromicity, a well-known fingerprint of stacking, is more
      pronounced in stacked xG-C and xA-T pairs than that in stacked G-C and A-T pairs,
      an index of enhanced stacking.

PMID- 18034471
TI  - Spinodal phase separation of unstable solid-state binary n-alkane mixtures.
AB  - Two mixtures of unequal chain length n-alkanes in which one component is
      deuterated have been investigated by infrared spectroscopy as they demixed. The
      measurements followed the band shapes of the scissors vibrations as a function of
      time. The band envelopes are analyzed as composites of a number of reference
      mixtures of known concentration. The unequal-chain mixtures separate into phases
      that slowly change their composition toward pure alkane phases. The method of
      analysis, which reveals local concentrations, should be generally applicable to
      polymethylene systems.

PMID- 18034472
TI  - Vanadium--benzimidazole-modified sDNA: a one-dimensional half-metallic
      ferromagnet.
AB  - We perform investigations on the structural, electronic, and magnetic properties
      of vanadium-stacked benzimidazole-modified single-stranded DNA (sDNA) using
      density functional theory. We find that the vanadium atoms aligned along the
      helical axis interact ferromagnetically. Furthermore, under the influence of an
      external electric field, these one-dimensional ferromagnets show half-metallic
      behavior, with the closing of the spin gap in the minority spin channel. The half
      metallic behavior of these systems crucially depends on the hybridization of the
      vanadium valence orbitals in the stacking direction. Also, we show that the sugar
      phosphate backbone does not influence the magnetic interactions, making the
      modified sDNA scaffold ideal for advanced spintronics applications.

PMID- 18034473
TI  - Prussian blue analogue CsFe[Cr(CN)(6)] as a matrix for the Fe(II) spin-crossover.
AB  - The origin of the intriguing spin-transition behavior of the Prussian blue
      analogue cesium iron hexacyanochromate CsFe[Cr(CN)6] has been investigated by
      means of correlated ab initio CASPT2 calculations. Using the smallest transiting
      core [Fe(NC)6]4-, the relative importance of the local ligand field and the
      Madelung field generated by the rest of the crystal was estimated. It is shown
      that in the presence of a frozen-charge environment, the high-spin state lies
      lower in energy than the low-spin state, thus excluding the possibility of
      observing a spin transition. In contrast, the charge reorganization in the
      environment evaluated from unrestricted periodic Hartree-Fock calculations
      creates a prerequisite for the spin-transition phenomenon. The influence of the
      disorder in the cesium ions' positions on the spin transition has been examined
      as a possible stabilizing factor of the low-spin state of [Fe(NC)6]4-. It is
      concluded that this experimentally observed disorder cannot account solely for
      the unprecedented behavior of the CsFe[Cr(CN)6] compound.

PMID- 18034474
TI  - Unprecedented gold-tellurolate clusters [Au(8)(mu-TeR)(8)(PR'(3))(4)].
AB  - The reaction of [AuCl(PR'3)] with KTeR, prepared from RTeTeR and K-selectride,
      gives the gold-tellurolate clusters [Au8(mu-TeR)8(PR'3)4] (R = Ph, Tol; PR'3 =
      PPh3, PPh2py) in high yield. This result contrasts with the one obtained from the
      reaction with thiolates or selenolates, from which mononuclear complexes are
      synthesized. The structures of these species have been determined and consist on
      three layers of gold and tellurium atoms in the ratio Au3Te2:Au2Te4:Au3Te2. There
      are short gold...gold interactions ranging from 2.9463(7) to 3.31132(7) A, and
      the clusters are composed of di- and tri-coordinated gold centers. The result is
      unprecedented in gold-chalcogenolate chemistry from which mononuclear species are
      expected and represents one of the few examples of gold-tellurolate derivatives.
      These species show an interesting luminescent behavior in the solid state (at 77
      K) and in solution (both at 298 and 77 K).

PMID- 18034475
TI  - Organo-Zintl clusters soluble in conventional organic solvents: setting the stage
      for organo-Zintl cluster chemistry.
AB  - Organo-Zintl cluster ions were synthesized by reactions of alkynes with Ge94-
      clusters in ethylenediamine. The triple bonds are hydrogenated to double bonds
      during the process. The resulting dial-kenylated species [RHC=CHGe9CH=CHR]2- have
      lower charge, their alkali-metal cations can be exchanged for tetralkylammonium
      cations, and the resulting compounds are soluble in nonpolar solvents. This was
      demonstrated with [H2C=CHGe9CH=CH2]2-, which was structurally characterized with
      [K-(18-crown-6)]+, [Me4N]+, and [Pr4N]+ as countercations. The solubility of its
      salt with [Oc4N]+ in various conventional organic solvents was studied.

PMID- 18034476
TI  - Both water- and organo-soluble supramolecular polymer stabilized by hydrogen
      bonding and hydrophobic interactions.
AB  - A new bis-urea based supramolecular polymer is reported and shown by
      viscosimetry, neutron scattering (SANS), and calorimetry (ITC) to self-assemble
      in a wide range of solvents, encompassing the polarity scale from water to
      toluene. The presence of both hydrogen-bonding and hydrophobic groups ensures
      that self-assembly occurs in water, aprotic polar solvents, and nonpolar
      solvents. Both the driving force for the assembly and the exact structure of the
      filaments is solvent dependent, but whatever the solvent, long rigid filaments
      are formed in dynamic equilibrium with the monomer.

PMID- 18034477
TI  - H2O nucleation around Au+.
AB  - First principles electronic structure calculations have been carried out to
      investigate the ground state geometry, electronic structure, and the binding
      energy of [Au(H2O)n]+ clusters containing up to 10 H2O molecules. It is shown
      that the first coordination shell of Au+ contains two H2O molecules forming a H2O
      Au+-H2O structure with C2 symmetry. Subsequent H2O molecules bind to the previous
      H2O molecules forming stable and fairly rigid rings, each composed of 4 H2O
      molecules, and leading to a dumbbell structure at [Au(H2O)8]+. The 9th and the
      10th H2O molecules occupy locations above the Au+ cation mainly bonded to one H2O
      from each ring, leading to structures where the side rings are partially
      distorted and forming structures that resemble droplet formation around the Au+
      cation. The investigations highlight quantum effects in nucleation at small sizes
      and provide a microscopic understanding of the observed incremental binding
      energy deduced from collision induced dissociation that indicates that
      [Au(H2O)n]+ clusters with 7-10 H2O molecules have comparable binding energy. The
      charge on the Au+ is shown to migrate to the outside H2O molecules, suggesting an
      interesting screening phenomenon.

PMID- 18034478
TI  - Molecular simulation of silica/surfactant self-assembly in the synthesis of
      periodic mesoporous silicas.

PMID- 18034479
TI  - Metallic and carbon nanotube-catalyzed coupling of hydrogenation in magnesium.
AB  - Synergistic effect of metallic couple and carbon nanotubes on Mg results in an
      ultrafast kinetics of hydrogenation that overcome a critical barrier of practical
      use of Mg as hydrogen storage materials. The ultrafast kinetics is attributed to
      the metal-H atomic interaction at the Mg surface and in the bulk (energy for
      bonding and releasing) and atomic hydrogen diffusion along the grain boundaries
      (aggregation of carbon nanotubes) and inside the grains. Hence, a hydrogenation
      mechanism is presented.

PMID- 18034480
TI  - Reversible gas uptake by a nonporous crystalline solid involving multiple changes
      in covalent bonding.
AB  - Hydrogen chloride gas (HCl) is absorbed (and reversibly released) by a nonporous
      crystalline solid, [CuCl2(3-Clpy)2] (3-Clpy = 3-chloropyridine), under ambient
      conditions leading to conversion from the blue coordination compound to the
      yellow salt (3-ClpyH)2[CuCl4]. These reactions require substantial motions within
      the crystalline solid including a change in the copper coordination environment
      from square planar to tetrahedral. This process also involves cleavage of the
      covalent bond of the gaseous molecules (H-Cl) and of coordination bonds of the
      molecular solid compound (Cu-N) and formation of N-H and Cu-Cl bonds. These
      reactions are not a single-crystal-to-single-crystal transformation; thus, the
      crystal structure determinations have been performed using X-ray powder
      diffraction. Importantly, we demonstrate that these reactions proceed in the
      absence of solvent or water vapor, ruling out the possibility of a water-assisted
      (microscopic recrystallization) mechanism, which is remarkable given all the
      structural changes needed for the process to take place. Gas-phase FTIR
      spectroscopy has permitted us to establish that this process is actually a solid
      gas equilibrium, and time-resolved X-ray powder diffraction (both in situ and ex
      situ) has been used for the study of possible intermediates as well as the
      kinetics of the reaction.

PMID- 18034481
TI  - Structured polymer grafts on diamond.
AB  - In this work, a facile method for the preparation of structured and functional
      polymer grafts on diamond surfaces is described. Uniform poly(styrene) (PS)
      grafts with a thickness of approximately 110 nm were created directly onto
      oxidized ultrananocrystalline diamond (UNCD) surfaces by the self-initiated
      photografting and photopolymerization of bulk styrene with UV irradiation. The
      stable covalent bonding of the PS grafts allows polymer analogue reactions with
      drastic reaction conditions without noticeable detachment of the polymer coating.
      Thus, various functionalities, such as nitro, sulfonic, and aminomethyl groups
      have been successfully incorporated to the polymer grafts. Furthermore, the
      reactivity contrast between hydrogenated and oxidized UNCD surfaces allows for
      the preparation of structured polymer grafts. Finally, we have demonstrated the
      good reactivity and accessibility of the incorporated pendant functional groups.

PMID- 18034482
TI  - Stereocontrolled and convergent entry to CF2-sialosides: synthesis of CF2-linked
      ganglioside GM4.

PMID- 18034483
TI  - Biosynthetic studies of platensimycin.

PMID- 18034484
TI  - Amplification of 4'-thioDNA in the presence of 4'-thio-dTTP and 4'-thio-dCTP, and
      4'-thioDNA-directed transcription in vitro and in mammalian cells.

PMID- 18034485
TI  - Using ferroelectric poling to change adsorption on oxide surfaces.
AB  - Adsorption has been invoked to explain many phenomena in ferroelectric materials
      including the unanticipated stability of ultrathin ferroelectric films; however,
      the intrinsic surface properties of ferroelectric oxides have been largely
      unexplored. Therefore, the effect of ferroelectric poling on the
      adsorption/desorption of two polar molecules, acetic acid and 2-propanol, and one
      nonpolar molecule, dodecane, on LiNbO3(0001) was compared. The two polar
      molecules were found to adsorb significantly more strongly on the positive
      surface. Temperature-programmed desorption (TPD) data yielded desorption pre
      exponentials of the two polar molecules more than 11 orders of magnitude lower
      than expected. Ferroelectric materials are also intrinsically pyroelectric, and
      it is shown that the unusually low desorption pre-exponentials can be explained
      by temperature dependent heats of adsorption that result from changes in the
      surface dipole as the samples are heated. This conclusion was supported by
      dodecane adsorption/desorption, which was independent of polarity with normal
      desorption pre-exponentials. The differences between the polar and nonpolar
      molecules indicate that interactions between polar molecules and ferroelectric
      surfaces are dominated by electrostatics. It is shown that adsorption energy
      differences between positive and negative surfaces are large enough to switch the
      polarity of ferroelectric thin films.

PMID- 18034486
TI  - Colloidal InP nanocrystals as efficient emitters covering blue to near-infrared.

PMID- 18034487
TI  - Thiophene-derivatized pybox and its highly luminescent lanthanide ion complexes.

PMID- 18034488
TI  - Electrospray ionization mass spectrometry of uniform and mixed monolayer
      nanoparticles: Au25[S(CH2)2Ph]18 and Au25[S(CH2)2Ph]18-x(SR)x.
AB  - New approaches to electrospray ionization mass spectrometry (ESI-MS)-with exact
      compositional assignments-of small (Au25) nanoparticles with uniform and mixed
      protecting organothiolate monolayers are described. The results expand the scope
      of analysis and reveal a rich chemistry of ionization behavior. ESI-MS of
      solutions of phenylethanethiolate monolayer-protected gold clusters (MPCs),
      Au25(SC2Ph)18, containing alkali metal acetate salts (MOAc) produce spectra in
      which, for Na+, K+, Rb+, and Cs+ acetates, the dominant species are
      MAu25(SC2Ph)182+ and M2Au25(SC2Ph)182+. Li+ acetates caused ligand loss. This
      method was extended to the analysis of Au25 MPCs with mixed monolayers, where
      thiophenolate (-SPh), hexanethiolate (-SC6), or biotinylated (-S-PEG-biotin)
      ligands had been introduced by ligand exchange. In negative-mode ESI-MS, no added
      reagents were needed in order to observe Au25(SC2Ph)18- and to analyze mixed
      monolayer Au25 MPCs prepared by ligand exchange with 4-mercaptobenzoic acid,
      HSPhCOOH, which gave spectra through deprotonation of the carboxylic acids.
      Adducts of tetraoctylammonium (Oct4N+) with -SPhCOO- sites were also observed.
      Mass spectrometry is the only method that has demonstrated capacity for measuring
      the exact distribution of ligand-exchange products. The possible origins of the
      different Au25 core charges (1-, 0, 1+, 2+) observed during electrospray
      ionization are discussed.

PMID- 18034489
TI  - Binary nanoparticle superlattices in the semiconductor-semiconductor system: CdTe
      and CdSe.
AB  - We report binary nanoparticle superlattices obtained by self-assembly of two
      different semiconductor quantum dots. Such a system is a means to include two
      discretized, quantum-confined, and complimentary semiconductor units in close
      proximity, for purposes of band gap matching and/or energy transfer. From a range
      of possible structures predicted, we observe an exclusive preference for the
      formation of Cuboctahedral AB13 and AB5 (isostructural with CaCu5) obtained in
      the system of 8.1 nm CdTe and 4.4 nm CdSe nanoparticles. For this system, a
      possible ionic origin for the formation of structures with lower packing
      densities was ruled out on the basis of electrophoretic mobility measurements. To
      understand further the principles of superlattice formation, we constructed space
      filling curves for binary component hard spheres over the full range of radius
      ratio. In addition, the pair interaction energies due to core-core and ligand
      ligand van der Waals (VDW) forces are estimated. The real structures are believed
      to form under a combined influence of entropic driving forces (following hard
      sphere space filling principles) and the surface (due to ligand-ligand VDW).

PMID- 18034490
TI  - The prion protein is a combined zinc and copper binding protein: Zn2+ alters the
      distribution of Cu2+ coordination modes.

PMID- 18034491
TI  - Mimicry of antimicrobial host-defense peptides by random copolymers.

PMID- 18034492
TI  - Sub-10 nm thick microporous membranes made by plasma-defined atomic layer
      deposition of a bridged silsesquioxane precursor.

PMID- 18034493
TI  - Selective formation of triplet alkyl nitrenes from photolysis of beta-azido
      propiophenone and their reactivity.
AB  - Photolysis of beta-azido propiophenone derivatives, 1, with built-in sensitizer
      units, leads to selective formation of triplet alkyl nitrenes 2 that were
      detected directly with laser flash photolysis (lambdamax = 325 nm, tau = 27 ms)
      and ESR spectroscopy (|D/hc| = 1.64 cm-1, |E/hc| = 0.004 cm-1). Nitrenes 2 were
      further characterized with argon matrix isolation, isotope labeling, and
      molecular modeling. The triplet alkyl nitrenes are persistent intermediates that
      do not abstract H-atoms from the solvent but do decay by dimerizing with another
      triplet nitrene to form azo products, rather than reacting with an azide
      precursor. The azo dimer tautomerizes and rearranges to form heterocyclic
      compound 3. Nitrene 2a, with an n,pi* configuration as the lowest triplet excited
      state of the its ketone sensitizer moiety, undergoes intramolecular 1,4-H-atom
      abstraction to form biradical 6, which was identified by argon matrix isolation,
      isotope labeling, and molecular modeling. beta-Azido-p-methoxy-propiophenone,
      with a pi,pi* lowest excited state of its triplet sensitizer moiety, does not
      undergo any secondary photoreactions but selectively yields only triplet alkyl
      nitrene intermediates that dimerize to form 3b.

PMID- 18034494
TI  - Fluorous metal-organic frameworks for high-density gas adsorption.

PMID- 18034496
TI  - An efficient synthetic approach to cyanocycline A and bioxalomycin beta2 via
      [C+NC+CC] coupling.

PMID- 18034495
TI  - Nano-flares: probes for transfection and mRNA detection in living cells.

PMID- 18034497
TI  - Enantioselective synthesis of aryl sulfoxides via palladium-catalyzed arylation
      of sulfenate anions.
AB  - Arylation of various sulfenate anions generated from beta-sulfinyl esters by
      retro-Michael reaction in the presence of palladium(0) and enantiopure ligands
      gave the corresponding aryl sulfoxides in enantio-enriched form. The Josiphos
      type ligand (R)-(S)-PPF-t-Bu2 turned out to be the best ligand tested, allowing
      ee's up to 83% in a predictable sense.

PMID- 18034498
TI  - New perspective for natural products synthesis: concise synthesis of (+)-sch
      642305 by chiral auxiliary multiuse methodology.
AB  - The synthesis of (+)-Sch 642305 is an example of chiral auxiliary multiuse
      methodology, which shows a new perspective for the synthesis of compounds with
      multiple asymmetric centers. Thus, (+)-Sch 642305 was concisely synthesized from
      the known compound. Every reaction is stereoselective, and the chiral nonracemic
      hydrobenzoin worked as chiral auxiliary for desymmetrization of diene, as a
      template for attaining regio- and stereoselective reactions, as an oxygen source
      at the C4-position, and as a protecting group of hydroxyl functions. Namely, the
      chiral auxiliary played a role in every step throughout the synthesis.
      Furthermore, the synthesis contains a new protocol for obtaining alpha'-alkylated
      enone compounds.

PMID- 18034499
TI  - Cloning, overexpression, purification, and characterization of S
      adenosylhomocysteine hydrolase from Corynebacterium efficiens YS-314.
AB  - The gene encoding S-adenosylhomocysteine hydrolase activity (SAHase: EC 3.3.1.1)
      from Corynebacterium efficiens (YS-314) was cloned and expressed as a fusion
      protein in Escherichia coli Rosetta (DE3). The analyzed nucleotide sequence of
      the cloned gene proved to be identical to those reported on the NCBI database.
      The recombinant enzyme is a tetramer, showing a molecular weight of approximately
      210 kDa, as estimated by gel filtration. The K(M) values of the enzyme for S
      adenosylhomocysteine (SAH), adenosine (Ado), and homocysteine (Hcy), were
      determined to be 1.4, 10, and 45 microM. The overexpression of the recombinant
      enzyme produced a high level of protein (>40 mg of protein per gram of wet cells)
      and revealed certain thermostability when characterized at temperatures above 40
      degrees C. It also showed a high capacity for the synthesis of SAH, thermal
      stability, and high kinetic similarity to human SAHase, indicating a high
      biotechnological and pharmacological potential.

PMID- 18034502
TI  - Two-dimensional confinement of nanorods in block copolymer domains.
AB  - Gold nanorods (NRs) self-orient during the self-assembly of a symmetric
      poly(styrene-b-methyl methacrylate) (PS-b-PMMA) film. The NRs are selectively
      sequestered and confined in lamellar PMMA domains, which are narrower than the NR
      length. This confinement orients 71% of NRs within +/- 5 degrees of the lamella
      plane. During solvent annealing, a gradient in the concentration of NRs is
      observed. This route to produce alternating layers containing conducting NRs
      separated by dielectric domains has the potential for fabricating self-assembled
      nanodevices.

PMID- 18034504
TI  - Bias-induced photoluminescence quenching of single colloidal quantum dots
      embedded in organic semiconductors.
AB  - We demonstrate reversible quenching of the photoluminescence from single CdSe/ZnS
      colloidal quantum dots embedded in thin films of the molecular organic
      semiconductor N,N'-diphenyl-N,N'-bis(3-methylphenyl)-(1,1'-biphenyl)-4,4'-diamine
      (TPD) in a layered device structure. Our analysis, based on current and charge
      carrier density, points toward field ionization as the dominant photoluminescence
      quenching mechanism. Blinking traces from individual quantum dots reveal that the
      photoluminescence amplitude decreases continuously as a function of increasing
      forward bias even at the single quantum dot level. In addition, we show that
      quantum dot photoluminescence is quenched by aluminum tris(8-hydroxyquinoline)
      (Alq3) in chloroform solutions as well as in thin solid films of Alq3 whereas TPD
      has little effect. This highlights the importance of chemical compatibility
      between semiconductor nanocrystals and surrounding organic semiconductors. Our
      study helps elucidate elementary interactions between quantum dots and organic
      semiconductors, knowledge needed for designing efficient quantum dot organic
      optoelectronic devices.

PMID- 18034500
TI  - Polyisoprenol specificity in the Campylobacter jejuni N-linked glycosylation
      pathway.
AB  - Campylobacter jejuni contains a general N-linked glycosylation pathway in which a
      heptasaccharide is sequentially assembled onto a polyisoprenyl diphosphate
      carrier and subsequently transferred to the asparagine side chain of an acceptor
      protein. The enzymes in the pathway function at a membrane interface and have in
      common amphiphilic membrane-bound polyisoprenyl-linked substrates. Herein, we
      examine the potential role of the polyisoprene component of the substrates by
      investigating the relative substrate efficiencies of polyisoprene-modified
      analogues in individual steps of the pathway. Chemically defined substrates for
      PglC, PglJ, and PglB are prepared via semisynthetic approaches. The substrates
      included polyisoprenols of varying length, double bond geometry, and degree of
      saturation for probing the role of the hydrophobic polyisoprene in substrate
      specificity. Kinetic analysis reveals that all three enzymes exhibit distinct
      preferences for the polyisoprenyl carrier whereby cis-double bond geometry and
      alpha-unsaturation of the native substrate are important features, while the
      precise polyisoprene length may be less critical. These findings suggest that the
      polyisoprenyl carrier plays a specific role in the function of these enzymes
      beyond a purely physical role as a membrane anchor. These studies underscore the
      potential of the C. jejuni N-linked glycosylation pathway as a system for
      investigating the biochemical and biophysical roles of polyisoprenyl carriers
      common to prokaryotic and eukaryotic glycosylation.

PMID- 18034505
TI  - A golden bullet? Selective targeting of Toxoplasma gondii tachyzoites using
      antibody-functionalized gold nanorods.
AB  - Conjugates of gold nanoparticles and antibodies have useful functionalities.
      Here, we show how they can be used to selectively target and destroy parasitic
      protozoans. Gold nanorods were conjugated with an anti-Toxoplasma gondii antibody
      and used to target the extracellular tachyzoite which is an infectious form of an
      obligate parasite Toxoplasma gondii. Subsequent laser irradiation was used to
      kill the targeted protozoans. This concept provides a new paradigm for the
      treatment of parasitic protozoans.

PMID- 18034506
TI  - All optical interface for parallel, remote, and spatiotemporal control of
      neuronal activity.
AB  - A key technical barrier to furthering our understanding of complex neural
      networks has been the lack of tools for the simultaneous spatiotemporal control
      and detection of activity in a large number of neurons. Here, we report an all
      optical system for achieving this kind of parallel and selective control and
      detection. We do this by delivering spatiotemporally complex optical stimuli
      through a digital micromirror spatiotemporal light modulator to cells expressing
      the light-activated ionotropic glutamate receptor (LiGluR), which have been
      labeled with a calcium dye to provide a fluorescent report of activity. Reliable
      and accurate spatiotemporal stimulation was obtained on HEK293 cells and cultured
      rat hippocampal neurons. This technique should be adaptable to in vivo
      applications and could serve as an optical interface for communicating with
      complex neural circuits.

PMID- 18034508
TI  - Immunological aspects of acute stroke: therapeutic implications.
AB  - Recent studies strongly suggest that cerebral ischaemia initiates a focal
      inflammatory response that results in significant secondary injury to brain
      tissue,thereby extending the ultimate size of a stroke. Factors involved in this
      cascade include the release of cytokines that cause a pro-inflammatory and
      prothrombotic state on cerebral vessel endothelium, the expression of leucocyte
      adhesion molecules, and the release of chemotactic factors allowing the migration
      of leucocytes into the area of injured brain tissue causing further damage.
      Animal studies have clearly demonstrated the detrimental effects of these
      inflammatory mediators in stroke models and additionally have shown dramatic
      reduction in infarct size using leucocyte adhesion modification and cytokine
      receptor blockade. The approach of modifying the effects of inflammatory
      cytokines and/or limiting leucocyte adhesion and migration into the region of
      injury holds great promise for identifying agents that will give significant
      neuronal protection following a stroke.

PMID- 18034509
TI  - Management of immune-mediated uveitis.
AB  - AbstractImmune-mediated uveitis is a collective term referring to a group of
      potentially blinding intraocular inflammations which may coexist with systemic
      inflammatory diseases. T lymphocytes appear to play an important pathogenic role
      in uveitis, and these cells are therefore the logical target of drug therapy.
      Corticosteroids act nonspecifically, but are highly effective in controlling the
      inflammation rapidly. They are administered locally when disease is confined to
      the anterior portion of the eye.However, posterior eye involvement often requires
      systemic corticosteroid therapy,carrying a high risk of serious adverse effects
      when used for extended periods. In this situation, steroid-sparing agents are
      used. Few relevant randomised, controlled clinical trials have been performed,
      and the choice of systemic immunosuppressive regimen is usually guided by
      individual patient characteristics, cost, drug availability and physician
      preference. Patients should actively participate in therapeutic decision-making.
      Our first choice for steroid-sparing medication is often methotrexate, an
      antimetabolite which carries a low risk of adverse reactions when appropriately
      prescribed and monitored, is relatively inexpensive, and has once-weekly ease of
      use. For more severe uveitis, we may combine the immunomodulating agent
      cyclosporin with methotrexate and a corticosteroid. Azathioprine and
      cyclophosphamide are other treatment options. Steroid-sparing drugs also have
      significant potential for causing adverse effects, albeit less frequently than
      corticosteroids. Future therapies aim to reduce this problem by increasing the
      specificity of the therapeutic action.

PMID- 18034510
TI  - Treatment of reactive arthritis: a practical guide.
AB  - AbstractReactive arthritis follows infections of the urogenital or enteric tract
      with bacteriasuch as Chlamydia, Yersinia, Shigella, Salmonella or Campylobacter.
      Typically,one knee or ankle are affected for weeks to several months, with up to
      20% ofpatients experiencing a chronic course of more than 1 year. The acute
      arthritis is treated nonspecifically with nonsteroidal anti-inflammatorydrugs
      (NSAIDs), local measures such as arthrocentesis, cold pads and rest of
      theaffected joint. If the triggering bacterium can be isolated in Chlamydia
      induced urogenital reactive arthritis, the infection should be
      treatedspecifically with antibacterials. Doxycycline 100mg twice daily, or
      erythromycin500mg 4 times daily, for 10 to 14 days are effective for Chlamydia,as
      is a single dose of azithromycin 1g. To prevent reinfections, the sexual
      partnershould be treated concurrently. Although remnants of bacteria and even
      bacterial RNA, suggesting live bacteria,can be demonstrated in the joint,
      treatment with antibacterials, even for long periods,does not show any benefit
      over placebo in enteric forms of reactive arthritis. For Chlamydia-induced
      reactive arthritis, antibacterials given for 3months in the absence of positive
      cultures from the urogenital tract may providesome benefit; however, further
      studies are needed before such treatment isrecommended. For reactive arthritis
      lasting longer than 6 months, patients may benefit fromsulfasalazine 2 g/day in
      addition to continued use of NSAIDs. In severalplacebo-controlled studies,
      sulfasalazine was well tolerated and moderately superiorto placebo. Other disease
      modifying antirheumatic drugs (DMARDs) can be tried inindividual patients who do
      not respond to sulfasalazine. However, since nocontrolled studies are available
      to date for DMARDs other than sulfasalazine, therisk-benefit ratio of such
      treatment should be carefully discussed with the patient.

PMID- 18034511
TI  - Aspirin-sensitive asthma: recent advances in management.
AB  - AbstractAspirin (ASA)-sensitive asthma is characterised by a typical sequence of
      symptoms, including intense eosinophilic inflammation of nasal and bronchial
      tissues. It is more commonly found in non-atopic, middle-aged female asthmatic
      patients with chronic rhino-sinusitis and/or nasal polyps. The lysine-aspirin
      bronchoprovocation test has become a widely used diagnostic test. When ASA
      sensitive asthma is confirmed, complete avoidance of ASA/non-steroidal anti
      inflammatory agents (NSAIDs) is crucial in preventing life-threatening adverse
      reactions. The basic principle of pharmacotherapy is step-wise treatment based
      upon anti-inflammatory therapy. Corticosteroids are the mainstay of therapy and
      anti-leukotriene agents may be indicated for treatment of the underlying
      disease.ASA desensitisation may reduce inflammatory mucosal disease
      symptoms,particularly in the nasal passage.

PMID- 18034512
TI  - Intranasal administration of influenza vaccines: current status.
AB  - AbstractThis review article focuses on intranasal immunisation against
      influenza,although it also encompasses antigen uptake and processing in the
      nasopharyngealpassages, host defence from influenza and current influenza
      vaccination practices.Improvement of current vaccination strategies is clearly
      required; current proceduresinvolve repeated annual injections that sometimes
      fail to protect the recipient. It isenvisaged that nonpercutaneous immunisation
      would be more attractive to potentialvaccinees, thus improving uptake and
      coverage. As well as satisfying noninvasivecriteria, intranasal influenza
      immunisation has a number of perceived immunologicaladvantages over current
      procedures. Perhaps one of the greatest attributes of thisapproach is its
      potential to evoke the secretion of haemagglutinin-specific IgAantibodies in the
      upper respiratory tract, the main site of viral infection. Inactivated influenza
      vaccines have the advantage that they have a long historyof good tolerability as
      injected immunogens, and in this respect are possibly morelikely to be licensed
      than attenuated viruses. Inert influenza vaccines are poormucosal immunogens,
      requiring several administrations, or prior immunologicalpriming, in order to
      engender significant antibody responses. The use of vaccinedelivery systems or
      mucosal adjuvants serves to appreciably improve theimmunogenicity of mucosally
      applied inactivated influenza vaccines. As is the casewhen they are introduced
      parenterally, inactivated influenza vaccines are relativelypoor stimulators of
      virus-specific cytotoxic T lymphocyte activity following nasalinoculation. Live
      attenuated intranasal influenza vaccines are at a far moreadvanced stage of
      clinical readiness (phase III versus phase I). With the use of liveattenuated
      vaccines, it is possible to stimulate mucosal and cell-mediatedimmunological
      responses of a similar kind to those elicited by natural influenzainfection. In
      children, recombinant live attenuated cold-adapted influenza viruses arewell
      tolerated. Moreover, cold-adapted influenza viruses usually stimulate
      protectiveimmunity following only a single nasal inoculation. Safety of
      recombinant liveattenuated cold-adapted influenza viruses has also been
      demonstrated in high riskindividuals with cystic fibrosis, asthma, cardiovascular
      disease and diabetes mellitus.They are not suitable for immunising
      immunocompromised patients, however, andare poorly efficacious in individuals
      with pre-existing immunity to strains closelyantigenically matched with the
      recombinant virus. According to the reviewedliterature, it is apparent that
      intranasal administration of vaccine as an aerosol issuperior to administration
      as nose drops. The information reviewed in this papersuggests that nasally
      administered influenza vaccines could make a substantialimpact on the human and
      economic cost of influenza.

PMID- 18034513
TI  - Prospects for a vaccine in allergic diseases and asthma.
AB  - Allergen-specific immunotherapy is widely used to treat allergic diseases, and
      current research is now focusing on the development of therapeutic vaccines
      acting on the IgE immune response following allergen challenge. The IgE immune
      response is dependent on genetic and environmental factors; production of IgE
      results from complex interactions among B cells, T cells, mast cells,
      basophils,surface and adhesion molecules and various cytokines. New vaccination
      methods under investigation involve allergen-specific or nonspecific methodology.
      Allergen-specific methods currently being developed include allergoids, passive
      saturation of effector cells, plasmid DNA immunisation and antigen-antibody
      complexes. The mechanisms of immunotherapy using allergen-specific methods differ
      with the allergens and the route of immunisation used (parenteral, intranasal,
      sublingual, oral or bronchial). Many vaccines being developed at present comprise
      synthetic, recombinant or highly purified subunit antigens, which although they
      have increased safety may also be less immunogenic.It is hoped that the addition
      of adjuvants will overcome this drawback. Methods of increasing the dose of
      allergen while reducing the possibility of an anaphylactic reaction include the
      use of non-anaphylactic isoforms of the allergens, alteration of the tertiary
      structure of the allergens and construction of minimal allergen-derived T cell
      peptides. Nonspecific approaches include humanised anti-IgE antibodies,moderation
      of the T(H)2 cytokine network and antisense oligodeoxynucleotide therapy.

PMID- 18034514
TI  - Could hormones make a difference in the treatment of juvenile rheumatoid
      arthritis?
AB  - Adrenal androgens dehydroepiandrosterone (DHEA; prasterone) and its sulphated
      form (DHEA-S) are among the most abundant hormonal steroids in men and
      nonpregnant women. Deficiencies of these adrenal androgens are associated with
      autoimmune disorders such as rheumatoid arthritis (RA). Recent studies from our
      laboratory have also identified low levels of adrenal androgens in the serum and
      synovial fluid of patients with juvenile rheumatoid arthritis (JRA). These
      findings support and complement those already published for RA and other
      autoimmune diseases. Because of the paucity of data on the hormonal status of
      patients with JRA, studies on the relationship between hypoandrogenicity and
      predisposition to develop JRA, and/or disease progression have not been
      conducted. In addition, despite the rapid expansion of research in the clinical
      use of these adrenal androgens in hyperlipidaemia, atherosclerosis, obesity,
      diabetes mellitus, insulin resistance and hypertension, their potential
      beneficial effects in JRA/RA have not been fully investigated. In fact, clinical
      trials of adrenal androgens in RA have only been conducted for the treatment of
      systemic lupus erythematosus. Further studies using prospective approaches are
      necessary to provide a unified consensus on the hormonal status of patients with
      JRA (as well as those with RA). This overview of our knowledge of the putative
      role(s) of hormones in arthritis will hopefully stimulate researchers in basic
      science and rheumatologists to synergistically collaborate in the effective
      translation of such knowledge to new clinical approaches.

PMID- 18034515
TI  - Phosphodiesterase type 4 inhibitors: potential in the treatment of multiple
      sclerosis?
AB  - Phosphodiesterases (PDEs) are involved in the regulation of intracellular levels
      of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic
      guanosine monophosphate (cGMP). These enzymes hydrolyse the cyclic nucleotides to
      the corresponding nucleoside 5'-monophosphates. Nine PDE subtypes have been
      identified; these differ in their substrate specificity and mode of activation.
      The type 4 PDE (PDE(4)) hydrolyses cAMP, is activated by elevated levels of cAMP,
      and is inhibited by rolipram. Inhibition of enzyme activity has been shown to
      modulate the activity of cells of the immune system. The production of tumour
      necrosis factor (TNF)(alpha) by activated monocytes and macrophages is inhibited,
      and cytokine secretion and proliferation of type 1 T helper cells are suppressed.
      Both immune cell activation and their concomitant induction of cytokine secretion
      are implicated in multiple sclerosis (MS), which is the major demyelinating
      disease of the central nervous system. Studies with the selective PDE(4)
      inhibitor rolipram in experimental autoimmune encephalomyelitis (an animal model
      of MS) in mice, rats and nonhuman primates have demonstrated the efficacy of the
      compound in this disease model, suggesting that PDE(4) inhibitors could
      ameliorate the clinical course of MS. Unfortunately, clinical trials with PDE(4)
      inhibitors revealed the major adverse effects of these drugs, namely nausea and
      vomiting. However, novel PDE(4) inhibitors, which target only a subpopulation of
      PDE(4) enzymes, may provoke fewer adverse effects. The efficacy of a PDE(4)
      inhibitor in MS still needs to be demonstrated in a well designed clinical trial.

PMID- 18034516
TI  - Anorectal Crohn's disease: surgical and medical management.
AB  - In some patients with Crohn's disease the anorectal complications are the major
      cause of symptoms and morbidity. Anorectal Crohn's disease may be present in
      patients with intestinal Crohn's disease, may be the initial manifestation of the
      disease, or rarely occurs without involvement of Crohn's disease elsewhere in the
      intestinal tract. The pathogenesis of these anorectal complications remains to be
      clarified. The anorectal examination is very important in the assessment of
      patients with suspected or documented inflammatory bowel disease. Meticulous
      physical examination, examination under anaesthesia and radiological imaging
      modalities may be utilised to specifically identify the location of abscesses and
      fistulae. Treatment strategy should be directed toward symptomatic relief; the
      most important symptom is pain. In most patients this pain will be attributable
      to an incompletely drained rectal abscess. Simple incision and drainage
      procedures are often all that is required as initial treatment of anorectal
      abscesses. Treatment of the anorectal fistulae that occur secondary to Crohn's
      disease requires combined medical and surgical therapy. Drug therapy is more
      often initiated for Crohn's disease that involves other areas of the
      gastrointestinal tract. The anorectal manifestations often respond to these same
      medications. Lay-open procedures (fistulotomies) are often all that is required
      surgically for simple (low) anorectal fistulae. High (complex) fistulae that
      involve large portions of the anorectal muscular ring are more difficult to
      treat. Patients with these fistulae must be treated on an individual basis,
      usually local surgical therapy combined with a medical regimen. Many surgical
      procedures are performed and many classes of medications are utilised on patients
      with these complex anorectal fistulae. Choosing the appropriate surgical and
      medical interventions is often quite difficult. Although sulfasalazine,
      mesalazine and corticosteroids have no lasting or maintenance value for fistulae,
      the immunosuppressive agents mercaptopurine, azathioprine and cyclosporin, the
      antibacterial metronidazole and the anti-tumour necrosis factor-alpha monoclonal
      antibody infliximab have varying degrees of effect. The goal of the combined
      regimen is to cure the fistula, or at least make it minimally symptomatic,
      without altering the patient's continence.

PMID- 18034517
TI  - Autoimmune adrenal insufficiency: recognition and management.
AB  - The main cause of Addison's disease is an autoimmune organ-specific destruction
      of the cells in the adrenal cortex by an autoreactive process of activated immune
      cells directed against the steroid-synthesising enzyme 21-hydroxylase. The
      diagnosis of Addison's disease is suspected in a patient presenting with symptoms
      of fatigue, bodyweight loss, anorexia, salt craving, and signs of low blood
      pressure and hyperpigmentation of the skin. Laboratory findings include
      electrolyte disturbances, and typically an elevated serum potassium level and
      sometimes a low serum sodium level is found together with low plasma levels of
      basal and corticotropin-stimulated hydrocortisone (cortisol). An aetiological
      diagnosis can rapidly be made using commercially available assays demonstrating
      the presence of autoantibodies directed against 21-hydroxylase. Determination of
      21-hydroxylase autoantibodies also permits early diagnosis before a complete
      adrenocortical destruction has occurred. Thus, a window of opportunity for an
      early immunomodulatory intervention therapy may exist. Patients presenting with
      an acute adrenocortical crisis should be treated with 100mg of hydrocortisone and
      saline intravenously without awaiting laboratory results. Maintenance therapy
      includes substitution of glucocorticoid and mineralocorticoid steroids, using
      divided and lower total dosages of glucocorticoids than previously used.

PMID- 18034518
TI  - Thrombolytics in acute ischaemic stroke: a guide to patient selection and optimum
      use.
AB  - Intravenously administered alteplase (recombinant tissue plasminogen activator;
      rtPA) is the only medical treatment that has been approved for the management of
      acute ischaemic stroke. Although rtPA has demonstrated efficacy in improving
      outcomes of patients with a wide range of neurological impairments, it cannot be
      given with impunity. Thrombolytic therapy is associated with a considerable risk
      of intracranial bleeding that is likely to be catastrophic. Careful selection of
      patients to treat and intensive ancillary care are the keys for successful
      administration of rtPA. An algorithm for selection is based on the interval from
      the onset of stroke, history of recent medical illnesses or use of medications,
      findings of the medical and neurological examinations and the results of
      laboratory and brain imaging studies. Because rtPA must be given within 3 hours
      of onset of stroke, most patients cannot be treated. Thus, additional therapies
      are needed for treatment of patients with acute ischaemic stroke.

PMID- 18034519
TI  - Quality of life in patients with chronic obstructive pulmonary disease: which
      drugs help most?
AB  - The treatment of chronic obstructive pulmonary disease (COPD) is receiving
      increasing attention since the burden of this disease is expected to rise on a
      global scale in the coming decades. Preventing deterioration of lung function
      parameters has been the main goal of research in COPD management. In practice,
      however, the success of drug treatment is not dependent on lung function only,
      but also relies on the patients' well-being. Therefore, an important role for
      health-related quality of life (HRQL) is emerging. Until now, several frequently
      prescribed drugs have been tested in trials using valid and disease-specific HRQL
      instruments. Evidence of beneficial effects on HRQL is available for the use of
      short-acting bronchodilators, theophylline and long-acting beta-adrenergic
      bronchodilators in the treatment of COPD. One source reported beneficial effects
      of inhaled corticosteroid treatment on HRQL. The value of these and other drugs
      in the management of COPD will need to be assessed in the coming years.

PMID- 18034520
TI  - Therapy for alpha1-antitrypsin deficiency: pharmacology and clinical
      recommendations.
AB  - Alpha1-antitrypsin (A1AT) deficiency is inherited as an autosomal codominant
      disorder characterised by reduced levels of A1AT in the serum. Low levels of A1AT
      in blood perfusing the lung cause low levels in the lung interstitium, making it
      susceptible to proteolytic damage from resident neutrophil elastase. A
      'protective threshold' serum A1AT level of 11 micromol/L has been identified by
      epidemiological studies as a minimum value below which there is an increased risk
      of emphysema. Intravenous augmentation therapy for patients with severe
      deficiency of A1AT has been shown to have biochemical efficacy. Although the
      clinical efficacy of intravenous augmentation therapy has not been demonstrated
      in a randomised clinical trial, available studies suggest that augmentation
      therapy is associated with a slowed rate of decline of lung function and enhanced
      survival. The criteria for patient selection include: age >18 years, serum A1AT
      level <or=11 micromol/L, a high-risk phenotype (usually PI*ZZ), and documented
      fixed airflow obstruction (consistent with chronic obstructive pulmonary
      disease). Although intravenous augmentation is currently the only form of
      specific therapy approved in the US, active research in the fields of aerosol and
      gene therapy promise to offer new treatment prospects. In this article, we review
      the available literature on A1AT augmentation therapy and discuss our
      recommendations.

PMID- 18034521
TI  - Relapsing-remitting multiple sclerosis: what is the potential for combination
      therapy?
AB  - Multiple sclerosis is now a treatable disease and several immunomodulating
      therapies exist, but their clinical efficacy is moderate and treatment failure
      during the course of the disease is an increasing problem. As agents with
      different targets are available, the question was raised whether combination of
      these therapies would: be safe;result in reduction of adverse effects; andprovide
      synergistic benefit by additive or complementary modes of action. The areas under
      clinical investigation are general immunosuppression as well as more targeted
      approaches that interfere with antigen presentation, immune cell transmigration,
      release of myelinotoxic factors or even axonal damage. Combination of these
      immunomodulatory drugs seems to be rational and promising. Nevertheless,
      combination therapies need to be studied in carefully designed clinical trials in
      selected patient populations in order to demonstrate additive or synergistic
      effects. This article will summarise current drug combination strategies in
      relapsing-remitting multiple sclerosis and provide an overview of the initial
      clinical trials.

PMID- 18034522
TI  - Current management strategies for the treatment and prevention of cytomegalovirus
      infection in solid organ transplant recipients.
AB  - Cytomegalovirus (CMV) infection in solid organ transplantation is associated with
      significant morbidity and mortality. Primary infection, secondary infection or
      superinfection may occur in this setting. Progression to disease may ensue with
      development of symptoms, with or without organ involvement. The mainstay of
      treatment of CMV disease is intravenous ganciclovir. Aside from protective organ
      matching and use of CMV-seronegative blood products, methods of preventing CMV
      infection and disease include passive immunisation with immunoglobulins,
      vaccination, and prophylaxis with antiviral agents such as aciclovir, oral or
      intravenous ganciclovir, and oral valaciclovir. A promising subunit vaccine is
      currently being investigated. Pre-emptive therapy is a form of prevention that is
      based either on the early detection of CMV or targeting of transplant recipients
      with risk factors for CMV. New sensitive laboratory assays, including the pp65
      antigenaemia assay, qualitative, quantitative and reverse-transcription
      polymerase chain reaction assays, hybridisation assays, and nucleic acid sequence
      based assays, have the ability to detect early CMV replication before disease
      becomes evident. These assays are being used as prospective surveillance tests,
      with pre-emptive therapy initiated when they become positive or demonstrate an
      increasing titre.

PMID- 18034523
TI  - Gene therapy for metabolic diseases of the liver.
AB  - Significant advances have been made in the field of liver-directed gene therapy.
      Many diseases are potential targets for gene therapy, including diseases that
      have exclusive liver involvement and those with systemic manifestations as a
      result of defective protein synthesis from the liver. Examples are Crigler-Najjar
      syndrome type 1, alpha(1)-antitrypsin deficiency and haemophilia A and B.
      Strategies for gene delivery include the use of viral and nonviral vectors. In
      addition to previously developed viral vectors, such as retroviruses,
      adenoviruses and adeno-associated viruses, new viral vectors such as lentiviruses
      are being investigated extensively. Nonviral vectors for gene delivery include
      liposomes and receptor-mediated gene therapy. A strategy to correct gene defects
      has been developed using chimaeric RNA/DNA oligonucleotides, and methods to
      inhibit aberrant or deleterious gene expression using ribozymes, antisense
      oligonucleotides and dominant-negative gene products are being developed.
      However, more research focusing on more efficient gene expression and safety will
      be required before gene therapy can be routinely applicable.

PMID- 18034524
TI  - Prevention of recurrence of hepatitis B virus infection after liver
      transplantation.
AB  - Hepatitis B virus (HBV) infection is still an important cause of cirrhosis,
      hepatocellular carcinoma and acute liver failure worldwide, and orthotopic liver
      transplantation (OLT) is the only effective treatment for many of these
      conditions. Until recently, however, OLT in patients with HBV infection was
      associated with a high rate of graft loss due to viral recurrence. The use of
      long term passive immunoprophylaxis with high dosage human polyclonal
      immunoglobulin against HBV (HBIg) has, for the first time, allowed favourable
      outcomes after OLT in a selected group of patients, but this treatment is
      associated with high cost and questionable efficacy in patients with high viral
      loads. In the last few years alternative approaches have arisen, namely the use
      of the reverse transcriptase inhibitor lamivudine and the induction of anti-HBV
      seroconversion by HBV vaccination as a means of discontinuing HBIg treatment. In
      this article we review the advantages and drawbacks of each of these prophylactic
      strategies, particularly emphasising the viability of administering HBV
      vaccination to these patients.

PMID- 18034525
TI  - Antisense oligonucleotides in cancer: recent advances.
AB  - The activation of dominant oncogenes and inactivation of tumour suppressor genes
      may result in cancer. These genetic events may represent novel targets for cancer
      therapy. Antisense nucleic acids can be used to modulate the expression of
      selected genes, and to suppress malignant behaviour in cancer cells.
      Nevertheless, in practice, the selection of suitable antisense targets still
      remains a trial-and-error procedure. Promising targets for antisense cancer
      therapy that have been extensively studied include proteases and protease
      receptors, telomerase, fusion genes, the Bcl family of proteins and various
      protein kinases. Combinations of antisense oligonucleotides with cytotoxic agents
      offer important advantages in cancer therapy. However, control oligonucleotides
      must be carefully chosen to separate the antisense effect from the many potential
      nonspecific effects. Several antisense drugs have been very effective in in vitro
      experiments, and have entered clinical trials. Successive generations of
      antisense drugs, including molecules with novel backbones or other structural
      modifications, chimeric oligonucleotides and peptide nucleic acids, are currently
      in development.

PMID- 18034526
TI  - Lanoteplase.
AB  - Lanoteplase is a recombinant plasminogen activator, which when administered as a
      single bolus intravenous injection, displays thrombolytic activity. In the phase
      II InTIME trial, lanoteplase dose-dependently increased reperfusion rates at 60
      and 90 minutes in patients with acute myocardial infarction and at 90 (but not
      60) minutes lanoteplase 120 kU/kg was significantly superior to alteplase in
      restoring TIMI grade 2 and 3 flow (in 83.0 and 71.4% of patients, respectively).
      Preliminary results from the phase III InTIME-II study showed that lanoteplase
      was as effective as alteplase in decreasing 30-day mortality. At 30 days, the
      combined incidence of death, reinfarction, major bleeding and heart failure was
      lower with lanoteplase 120 kU/kg than with alteplase 100mg. From preliminary
      results of the large InTIME-II study, lanoteplase 120 kU/kg showed a greater
      incidence of intracranial haemorrhage and mild bleeding than alteplase <or=100mg,
      but a similar incidence of stroke. The smaller InTIME study showed a tendency for
      fewer adverse events with lanoteplase.

PMID- 18034527
TI  - Lanoteplase: a viewpoint by Robert Neil Doughty.

PMID- 18034528
TI  - Lanoteplase: a viewpoint by Uwe Zeymer and Karl-Ludwig Neuhaus.

PMID- 18034529
TI  - Melanoma vaccines in development: looking to the future.
AB  - There is a body of evidence indicating that melanoma is an antigenic tumour.
      Since the efficacy of standard therapy in advanced stages of melanoma is rather
      poor, experimental immunotherapy aims to target this aggressive neoplasm. After
      the identification of several melanoma antigens, vaccination trials have been
      initiated in patients with metastatic disease using peptides, dendritic cells and
      gene therapy approaches including viral vectors or naked DNA. If the problems in
      inducing a constant and potent T cell response are solved, the stability of
      melanoma antigens and their presentation will decide whether these treatment
      approaches will reach significant relevance in daily clinical practice.

PMID- 18034530
TI  - Anti-interleukin-12 antibody: potential role in preventing relapses of multiple
      sclerosis.
AB  - Multiple sclerosis is an inflammatory demyelinating disorder of the central
      nervous system. Immunological evidence from patients with multiple sclerosis and
      experimental models suggests that the cytokine interleukin-12 (IL-12) plays an
      important role in the pathogenesis of inflammatory demyelination. In experimental
      autoimmune encephalomyelitis, an animal model of multiple sclerosis, antibodies
      that block IL-12 can prevent relapses of the disease. Anti-IL-12 antibodies
      present a novel approach for preventing relapses in multiple sclerosis.

PMID- 18034531
TI  - Common variable immunodeficiency: an update on therapeutic approaches.
AB  - Common variable immunodeficiency (CVID) is not a homogeneous disease, as has
      become clear from recent scientific studies. This makes the interpretation of
      studies of clinical therapeutics difficult to assess and raises questions about
      historical case reports. The evidence for the optimum use of replacement
      immunoglobulin in CVID is reviewed. This therapy represents the current gold
      standard, despite attempts to use other immunostimulatory compounds. Questions of
      product properties, product selection, adverse events and infectious risks are
      addressed. Products are not interchangeable and have different physicochemical
      characteristics. Despite intravenous immunoglobulin being in use for 20 years,
      there are still unanswered questions over dose and target trough IgG levels,
      particularly with respect to patients with established lung disease. The
      management of organ-based complications of CVID is discussed. This includes the
      treatment of unusual infections such as mycoplasmas and enteroviruses, which are
      specific to antibody deficiency. The diagnosis and treatment of the granulomatous
      disease of CVID is discussed. The role of surgery, including lung
      transplantation, in the management of CVID complications is reviewed. There are
      few available data on optimum strategies for antibiotic usage for bacterial
      infective complications and it is clear that present regimens, at least in severe
      recurrent sinus disease, are not consistently effective. Better clinical trials
      are required to identify appropriate regimens and validate or disprove widely
      held assumptions about therapy in CVID. Despite advances in diagnosis and
      management, there is abundant evidence in the UK that patients do not yet receive
      rapid diagnosis and optimum therapy, even within the limited published data
      currently available. This leads to considerable avoidable morbidity and
      mortality.

PMID- 18034532
TI  - Use of thalidomide in dermatological indications.
AB  - The resurgence of interest in thalidomide in the last decade has been remarkable.
      Thalidomide has established its own niche market particularly for the
      dermatological manifestations associated with HIV, Behcet's disease, graft-versus
      host disease and systemic lupus erythematosus. To a large extent this has
      resulted from initial empirical uncontrolled studies in conditions resistant to
      other drug therapies. Appropriate trials are now being published for most of the
      prevalent indications. Thalidomide produces partial inhibition of tumour necrosis
      factor-alpha production in vivo but recent data reveals that it can also act as a
      co-stimulatory molecule for T cell activation in vitro, resulting in increased
      production of interleukin-2 and interferon-gamma. Hence in addition to monocyte
      inhibitory activity, thalidomide can exert a co-stimulatory or adjuvant-like
      effect on T cell responses. The unraveling of the molecular basis of
      thalidomide's therapeutic effects would suggest that an expansion of the use of
      thalidomide and its analogues in other conditions is highly likely. It remains
      imperative, however, that physicians using this fascinating drug are familiar
      with its risks and adverse effects.

PMID- 18034533
TI  - Qualitative and quantitative assessment of the benefit-risk ratio of medium
      potency topical corticosteroids in vitro and in vivo: characterisation of drugs
      with an increased benefit-risk ratio.
AB  - Corticosteroids are widely used for the treatment of inflammatory skin disorders.
      However, systemic and local adverse drug reactions, especially skin atrophy, are
      potential complications that limit their use. Several attempts have been made to
      increase the safety of topical corticosteroid treatment, including new
      application schedules, special vehicles and new agents. In particular, the group
      of hydrocortisone and prednisolone double esters, with prednicarbate as the first
      and most often prescribed representative, seem to be equipotent alternatives to
      the gold standard betamethasone 17-valerate with respect to anti-inflammatory
      activity. At the same time, these new agents induce less skin atrophy, which may
      result from a unique skin metabolism and a specific influence on the cytokine
      network in the epidermis and dermis. On the basis of these effects, a new
      approach to in vitro quantification of the benefit-risk ratio has been developed.
      As already suggested by investigations in human volunteers, the benefit-risk
      ratio of the new compounds appears to be increased. Therefore, recent research
      has focused on drugs that selectively modulate cytokine release.

PMID- 18034534
TI  - Exhaled nitric oxide levels in childhood asthma: a more reliable indicator of
      asthma severity than lung function measurement?
AB  - The level of exhaled nitric oxide (NO) has been demonstrated to reflect the
      degree of airway inflammation in patients with asthma and to be related to the
      severity of asthma, as well as to the efficacy of treatment. In contrast, lung
      function tests provide information about airway volumes and flows reflecting the
      level of airway obstruction, but do not allow any direct information about the
      degree of airway inflammation. Several studies have evaluated the relationships
      between the level of airway inflammation assessed by exhaled NO and the levels of
      airway obstruction and/or bronchial hyperresponsiveness in asthmatic adults and
      children. These studies highlight the complex pathophysiology of asthma and
      suggest that exhaled NO may have a promising role in addition to lung function
      measurement in the evaluation of asthma severity in children.

PMID- 18034535
TI  - Recombinant clotting factors: a review of current clinical status.
AB  - In the short time span since the cloning of the human genes for factors VIII, IX
      and VII, recombinant factor (rF)VIII, rFIX and rFVIIa concentrates have been
      produced and standardised, have entered clinical trials, and have been licensed
      for clinical use in the US, Europe and elsewhere. Even more recently, a new
      generation of recombinant clotting factor concentrates has emerged, including
      rFVIII concentrates formulated with sucrose rather than human serum albumin and a
      B-domain-deleted rFVIII preparation. Additionally, rFVIII concentrates which
      contain no human or animal proteins in their manufacture are in development, as
      is a combination rFVIII plus recombinant von Willebrand factor concentrate. The
      clinical experience in previously treated patients with each of the existing
      recombinant products has documented that inhibitor development is not increased
      with any of them. As expected, there has been no reported instance of disease
      transmission with any of the recombinant clotting factor concentrates. Since
      their introduction, usage of each of the recombinant clotting factor concentrates
      has dramatically increased in countries where these products are licensed,
      available and affordable.

PMID- 18034536
TI  - Interferon-alpha alone versus interferon-alpha plus ribavirin in patients with
      chronic hepatitis C not responding to previous interferon-alpha treatment.
AB  - OBJECTIVE: To study the effects of monotherapy with leucocyte interferon-alpha
      (IFNalpha) versus IFNalpha + ribavirin in patients with chronic hepatitis C who
      were nonresponders to previous courses of recombinant or lymphoblastoid IFNalpha.
      DESIGN AND SETTING: This was a nonblind randomised study of outpatients at 3
      centres in Palermo, Sicily, Italy. PATIENTS AND PARTICIPANTS: We recruited 72
      patients (48 males, 24 females), mean age 48.8 +/- 6.6 years (range 31 to 63
      years), with biopsy-proven chronic hepatitis C, predominantly genotype 1b.
      INTERVENTIONS: 24 patients (group A) received IFNalpha 6MU 3 times weekly for 6
      months, and 48 patients (group B) received IFNalpha 6MU 3 times weekly +
      ribavirin 1200 mg/day for 6 months. ALT levels and adverse effects were monitored
      monthly, and hepatitis C virus (HCV) RNA levels were measured at study entry, at
      the end of treatment and after a 6-month follow-up. RESULTS: At baseline all
      patients were HCV-RNA positive and had ALT levels greater than twice normal. Mean
      post-treatment serum HCV-RNA levels were below baseline in group A, but the virus
      was eradicated in only 1 patient; 6 patients had normalised serum ALT levels. In
      group B at end of treatment, 12 patients were negative for HCV-RNA and serum ALT
      levels were normal in 18. At follow-up, all group A patients had elevated ALT
      levels and positive HCV-RNA. In group B, 3 patients were still negative for HCV
      RNA and 4 had normal ALT. In 4 patients in group B, therapy was suspended because
      of anaemia, depression and decrease in neutrophil count; a flu-like syndrome was
      recorded with no frequency difference between groups. CONCLUSIONS: These results
      suggest that patients with chronic hepatitis C unresponsive to IFNalpha
      monotherapy could benefit from combination therapy with IFNalpha + ribavirin.

PMID- 18034537
TI  - Opening the flood gates: interferon-alpha treatment for Sjogren's syndrome.
AB  - Interferon (IFN)-alpha is the main IFN produced in response to viral infection.
      Low levels of IFNalpha can be detected in nasal secretions after exposure to
      viruses in vivo. Radioimmunoassay has shown that endogenous IFNalpha is low in
      children, reaches a peak in young adults, and gradually declines with aging.
      Importantly, this endogenous IFNalpha is significantly decreased in patients with
      Sjogren's syndrome (SS). IFNalpha has been tested as a therapeutic agent in
      patients with SS. Intramuscular human leucocyte IFNalpha increases saliva
      production significantly in patients with SS. Improvements have been noted in
      lacrimal function and in dryness symptoms. Since IFNalpha infrequently induces
      autoimmune phenomena and high dose IFNalpha treatment sometimes has a serious
      adverse event profile, treatment focus has shifted to use of low dose orally
      administered IFNalpha. In a single-masked controlled trial, 60 patients with SS
      randomly received natural human IFNalpha 150IU 3 times a day in an oral lozenge
      formulation or sucralfate as control for 6 months. At study end, 15 (50%) of the
      30 IFNalpha-treated patients had saliva production increases at least 100% above
      baseline. IFNalpha treatment was well tolerated and no patients withdrew. Labial
      minor salivary gland biopsies indicated significant decreases in lymphocytic
      infiltration accompanied by a significant increase in intact salivary gland
      tissue after 6 months of treatment. In another 12-week double-masked, randomised,
      placebo-controlled trial, stimulated saliva production in patients with SS
      receiving IFNalpha lozenges 150IU 3 times daily was significantly increased. This
      dosage was also suggestive of benefit for 5 of 7 subjective measures of oral and
      ocular comfort. The tolerability profile of these low dose oral IFNalpha lozenges
      is excellent; no serious adverse events have been recorded. Adverse effects were
      generally mild and there were no clinically significant changes in laboratory or
      clinical safety measures. Low oral doses of natural human IFNalpha thus appear to
      improve secretory function and relieve dryness in patients with SS without
      causing significant adverse events. Endogenous or orally administered IFNalpha
      may activate oropharyngeal lymphoid and epithelial cells and induce production of
      potent soluble factors which could mediate immunological reactivity. It has been
      suggested that IFNalpha/beta potentiates clonal expansion and survival of CD8 T
      cells. Stimulating effects have also been demonstrated on natural killer cell
      activity, which has been shown to be depressed in patients with SS. It is likely
      that some combination of these immunological effects results in anti-inflammatory
      activity and ameliorates signs and symptoms of SS.

PMID- 18034538
TI  - Management of medication noncompliance in solid-organ transplant recipients.
AB  - Solid-organ transplantation has emerged as one of the most significant medical
      advances in the management of end-stage organ disease to date. However, a long
      term successful outcome after transplantation relies heavily upon the extended,
      if not lifelong, intake of immunosuppressive medication. Noncompliance with the
      medication regimen may have devastating effects on the graft and the patient.
      Furthermore, the effects of noncompliance place an additional burden on the
      medical resources available and the already scarce organ supply. The magnitude of
      post-transplant noncompliance and factors associated with noncompliance with
      various immunosuppressant drugs are reviewed. Patient, physician, social and
      family relationships interact in a complex manner in the post-transplant scenario
      and problems here could underlie noncompliance. The paper also includes a review
      of the methods of evaluating and monitoring noncompliance. Preventive and
      remedial measures that may help the transplant team to effectively manage this
      problem are suggested. The multidisciplinary nature of post-transplant patient
      management and the need for a cohesive approach toward the patient is emphasised.
      With the identification of patients at higher risk for noncompliance, close
      monitoring and early intervention, it may be possible to effectively control the
      effects of noncompliance until newer strategies are developed which permit
      immunosuppression-free transplantation.

PMID- 18034539
TI  - Management of psoriasis: the position of retinoid drugs.
AB  - Oral synthetic retinoids have been established as effective systemic therapy for
      psoriasis since their introduction for clinical use in the 1970s; a compound for
      topical use, tazarotene has been recently marketed. Despite the demonstrated
      clinical success of retinoid therapy in psoriasis, its mechanism of action has
      not been fully elucidated, and investigators are confronted with two paradoxes.
      One is that the binding of retinoids to nuclear retinoic acid receptors (RARs)
      does not match their therapeutic efficacy: acitretin activates the three receptor
      subtypes, RAR-alpha, -beta and -gamma, without measurable receptor binding,
      whereas tazarotene preferentially binds to and activates RAR-beta and -gamma in
      preference to RAR-alpha. The other is that there is already increased formation
      of retinoic acid in the psoriatic lesion. Answering these questions should result
      in better use of these drugs in the treatment of psoriasis. Oral administration
      of acitretin remains one of the first therapeutic choices for severe psoriasis,
      particularly in association with ultraviolet light therapy, of which it may
      decrease the carcinogenic risk. Topical tazarotene is suitable for moderate
      plaque psoriasis. Its efficacy and tolerability can be enhanced by the addition
      of topical corticosteroids; its irritative potential is counterbalanced by a
      sustained therapeutic effect after the treatment is stopped.

PMID- 18034540
TI  - Timing of vaccinations in premature infants.
AB  - Preterm infants have immunological immaturities that may impact on vaccine
      responses. Larger premature infants mount immune responses to vaccines that are
      similar to those of full term infants, but very premature infants (<30 weeks'
      gestation at birth) have specific defects in vaccine responsiveness. The
      immunogenicity of diphtheria, tetanus and pertussis antigens is similar in full
      term and premature infants. Poliovirus vaccines, however, do not always stimulate
      adequate antibody responses in premature infants. The immunogenicity of
      Haemophilus influenzae type b conjugate vaccines varies widely in studies of
      premature infants, and may be affected both by choice of conjugate protein and by
      the infant's overall health. Hepatitis B vaccine given at birth appears poorly
      immunogenic in infants with birthweights <1750g, with delay in the administration
      of the first dose yielding improved immunogenicity. Sick premature infants may
      suffer increased episodes of apnoea following vaccine administration. Persistence
      of immunity, the quality of the immune response, and evaluation of the specific
      tolerability and immunogenicity of new vaccines in premature infants are topics
      needing further research. Although it is generally true that recommendations for
      vaccination of term infants are applicable to premature infants, it is not always
      specifically true. Optimal care of preterm infants requires attention to the
      exceptions to this generalisation.

PMID- 18034541
TI  - Impact of inhaled and intranasal corticosteroids on the growth of children.
AB  - Since inhaled and intranasal corticosteroids may be systemically bioavailable,
      risk of growth suppression cannot be ruled out in children treated with these
      compounds. The mechanisms by which exogenous corticosteroids can cause growth
      suppression may be multifactorial, involving influences on growth hormone
      secretory profiles and insulin-like growth factor-I activity, direct effects on
      the epiphyseal growth plate, and effects on bone and collagen turnover. When
      studies on growth in children treated with inhaled and intranasal corticosteroids
      are interpreted, it is important to discriminate between data on the final
      outcome of growth (adult height) and data on growth rate. No firm conclusions can
      be drawn on adult height from the available data. While the data on children
      treated with inhaled corticosteroids appear reassuring, there are no peer
      reviewed studies on the final height of children treated with intranasal
      corticosteroids. The possibility of additive effects on the final height or
      growth rate of children receiving intranasal plus inhaled corticosteroids has
      also not been studied. When assessing the risk of growth rate suppression,
      specific corticosteroids, doses and inhaler systems must be evaluated separately.
      Standard paediatric doses of inhaled corticosteroids (budesonide 200 to 400
      microg/day delivered from a metered dose inhaler with a spacer, dry powder
      budesonide 200 microg/day, or dry powder fluticasone propionate 200 microg/day)
      do not affect growth rate when a twice daily administration regimen is used. The
      risk of growth rate suppression in children treated with inhaled budesonide
      depends on the dosage and may become significant with 800 microg/day administered
      with a spacer, or with 400 microg/day administered with a dry powder device. When
      high doses of inhaled corticosteroids are used, the risk of adverse effects on
      growth rate can be reduced by once daily dosage in the morning. In fact,
      intranasal mometasone furoate 100 and 200microg from an aqueous pump spray and
      dry powder budesonide 200 and 400microg once daily in the morning have been found
      not to affect growth rate. Sensitivity to adverse effects on growth rate may vary
      between individuals. If growth suppression is detected, 'catch-up growth' may be
      expected when the dose of the inhaled or intranasal corticosteroid is reduced or
      other treatment modalities are introduced. Inhaled or intranasal corticosteroids
      should not be withheld from children with asthma or rhinitis. Topical
      corticosteroids should be given in doses that control disease symptoms; however,
      height measurements should be performed regularly in children receiving
      corticosteroids.

PMID- 18034542
TI  - Biological approaches to treatment of head and neck cancer.
AB  - There are few options for the treatment of advanced squamous cell carcinoma of
      the head and neck (SCCHN). Chemotherapy in such patients is not associated with
      survival improvement. However, recent reports suggest that approaches involving
      biological therapy may provide some benefits. The most promising therapeutics,
      currently in phase III investigation, involve p53 gene replacement with
      adenoviral vectors and tumour lysis with tumour-specific oncolytic viruses (ONYX
      015). Improved understanding of cancer immunology appears to be opening doors
      through targeting tumour antigens and upregulation of co-stimulatory molecules
      with the use of gene therapy. Cellular therapy trials and other approaches
      involving antiangiogenic factors, superoxide dismutase and the thymidine kinase
      gene in SCCHN remain preliminary.

PMID- 18034543
TI  - Are there differences in methotrexate kinetics between responding and
      nonresponding patients with rheumatoid arthritis?
AB  - OBJECTIVE AND STUDY DESIGN: The purpose of this study was to investigate the
      presence of a correlation between methotrexate pharmacokinetics and clinical
      efficacy in patients with rheumatoid arthritis. PATIENTS AND METHODS: The study
      was carried out in 29 patients with rheumatoid arthritis. The patients received
      intramuscular methotrexate (MTX) 7.5mg once a week for 8 weeks. Before and 0.5,
      1, 2, 3, 4, 6, 9, 12 and 24 hours after the first administration, MTX serum
      concentrations were measured and pharmacokinetic investigations were carried out.
      The clinical status of the disease was evaluated before and after 8 weeks of
      therapy. In addition, before and after 2 and 8 weeks of treatment, the patients
      were monitored for a complete biochemical profile. After 8 weeks of treatment, on
      the basis of improvement in clinical parameters, the patients were designated
      responders or nonresponders. RESULTS: A clinical response was obtained in 62% of
      patients (18 patients responded and 11 did not) and was associated with a low
      incidence of adverse effects. There were no differences in the pharmacokinetic
      parameters of MTX between the 2 groups of patients (responders vs nonresponders),
      except that t(max) was significantly higher in nonresponders than in responders
      (p < 0.05). CONCLUSIONS: These data confirm the efficacy and tolerability of low
      dose MTX in patients with rheumatoid arthritis in the short term, but appear to
      exclude a relationship between MTX kinetics and clinical response.

PMID- 18034544
TI  - Delivery of immunoprophylactics in transgenic plants: current status.
AB  - The search for economic alternatives for the production of recombinant
      immunoprophylactics has resulted in the concept of generating them in plants at
      relatively low cost. Two basic strategies are employed: the expression of
      recombinant antigens or antibodies in transgenic plants, or the presentation of
      small antigen epitopes on the surface of genetically modified plant viruses. Both
      approaches have resulted in the production of biologically active
      immunoprophylactics that have been shown in animal studies to protect from the
      development of disease symptoms. An especially interesting feature of producing
      vaccines in edible plant parts is the potential to use the transgenic plant as a
      vehicle for oral delivery. Substantial progress has been made over the past few
      years, and the first clinical trials have demonstrated the potential of this new
      technology. Future challenges are to express the immunoprophylactics at
      controlled, high concentrations in plants that could be grown locally where they
      are needed, and to develop easy and standardised administration procedures.

PMID- 18034545
TI  - Leptin in the pathophysiology of human obesity and the clinical potential of
      leptin-based therapy.
AB  - Leptin is a circulating hormone that is secreted in proportion to fat mass. It
      can reduce bodyweight by activating signalling molecules in the brain. Leptin
      appears to affect bodyweight primarily by decreasing food intake; there is no
      direct evidence that it significantly influences energy expenditure in humans.
      Its discovery in 1994 raised the possibility that it may be a useful, satiety
      inducing, anti-obesity drug. However, treating obese patients with leptin alone
      does not induce substantial bodyweight loss because most obese patients are
      insensitive to leptin and are not leptin deficient. In combination with diet
      therapy, however, leptin treatment has the potential to eliminate the dramatic
      fall in circulating leptin levels (and the subsequent increase in hunger) caused
      by calorie restriction. Used in this manner, leptin may play a very useful role
      in the maintenance of bodyweight loss. In the future, leptin analogues and the
      development of compounds that increase leptin sensitivity may also prove to be
      valuable therapeutic approaches for obesity.

PMID- 18034546
TI  - The potential of newer immunomodulating drugs in the treatment of uveitis: a
      review.
AB  - Uveitis, or intraocular inflammation, remains an ongoing challenge to
      ophthalmologists and patients alike. In most patients, uveitis is limited to the
      anterior ocular structures and is readily managed with topical steroids. The
      inflammatory process can extend behind the lens to involve the pars plana, the
      vitreous cavity, the choroid and the retina. These intermediate and posterior
      uveitides are relatively rare but contribute disproportionately to visual
      morbidity and present serious diagnostic and therapeutic difficulties. Systemic
      steroids constitute the first line of treatment for most sight-threatening
      uveitides. Their long term use is limited by universal and debilitating adverse
      effects. Second-line, steroid-sparing agents allow a reduction in steroid dosage.
      Cyclosporin and azathioprine are the main steroid-sparing agents currently in
      use. However, these compounds are limited by a narrow therapeutic window and
      significant adverse effects. This paper offers a brief discussion of some of the
      immune mechanisms involved in the pathogenesis of uveitis and reviews categories
      of investigational compounds. Inhibitors of T cell function: tacrolimus
      (previously FK506), licensed for use in liver transplantation, and sirolimus
      (rapamycin) are macrolide antibiotics. Sirolimus is a functional cytokine
      antagonist and in vitro studies suggest it could be up to 100 times more potent
      than cyclosporin. Drug synergy between sirolimus and cyclosporin has been
      demonstrated, resulting in immunosuppression at lower drug doses and with fewer
      adverse effects. Nucleotide synthesis inhibitors: mycophenolate mofetil (MMF) and
      leflunomide. Human lymphocytes are only able to synthesise nucleic acids de novo.
      Having no alternative or 'salvage' pathway, they are exquisitely sensitive to
      interference with the de novo nucleotide synthesis enzymatic pathway. MMF is a
      purine synthesis inhibitor. Compared to other purine inhibitors, early data
      suggest that MMF is more efficacious and less toxic than azathioprine.
      Leflunomide is an inhibitor of pyrimidine synthesis. Monoclonal surface receptor
      antibodies and immunoadhesins: the IL-2 receptor is essential for clonal
      expansion of activated T cells; this has led to the development of anti-IL-2
      receptor antibodies. Daclizumab is a genetically engineered humanised IgG1
      monoclonal antibody. In conjunction with cyclosporin, it significantly reduces
      renal allograft rejection rates and is also showing promise in the treatment of T
      cell mediated autoimmune disorders. The mechanism of action of monoclonal
      antibodies to other pro-inflammatory cytokines such as TNFalpha and IL-12 and
      data from animal and human uveitis trials are also discussed. Finally, new
      avenues of research in immunopharmaco-modulation are mentioned.

PMID- 18034547
TI  - Intestinal Behcet's disease: epidemiology, pathophysiology and potential of
      mesalazine.
AB  - Behcet's disease (BD) is a systemic inflammatory disease of unknown origin that
      affects various parts of the body. In some patients, the prognosis of the disease
      appears to be altered by the involvement of the intestine (intestinal BD). In
      intestinal BD, deep ulcers develop in the gastrointestinal tract, typically in
      the ileocaecum. Intestinal lesions in patients with BD are much more common in
      countries in the Far East, especially Japan. The tissue damage occurring in
      patients with BD is believed to be caused by oxygen radicals, which are promoted
      by proinflammatory cytokines and arachidonic acid metabolites. New formulations
      of mesalazine (5-aminosalicylic acid; 5-ASA) are now available for the treatment
      of intestinal BD. Mesalazine breaks the chain reaction of free radical
      production. Mesalazine may provide an effective treatment for the promotion of
      long term healing of mucosal ulceration of the intestine in patients with BD.

PMID- 18034548
TI  - Optimisation of the treatment of acute gout.
AB  - Most of the drugs prescribed to treat acute gouty attacks were used before the
      introduction of modern clinical trials. Thus, there are few well-designed studies
      available to evaluate these drugs. Nevertheless, worldwide clinical experience
      supports the use of most nonsteroidal anti-inflammatory drugs (NSAIDs),
      colchicine and corticosteroids in the treatment of acute gout. Colchicine has
      been widely used but toxicity, especially gastrointestinal adverse effects, are a
      major concern. Therapeutic regimens involving hourly or 2-hourly administration
      were based on the short initial half-life of colchicine in plasma. Other therapy
      schedules, such as early 8-hourly administration, may be equally effective and
      have fewer adverse effects. Unfortunately, comparative studies to investigate
      this have not been performed. Colchicine should not be prescribed to patients
      with either severe renal insufficiency or combined hepatic-renal insufficiency.
      Doses should be halved in patients with moderate renal function impairment.
      NSAIDs are the most widely prescribed drugs in the treatment of acute gout. Few
      comparative data are available, but any of the most potent NSAIDs are probably
      useful in the control of pain and inflammatory signs of acute gouty arthritis.
      Pharmacokinetic properties should be taken into account when selecting an NSAID
      for the treatment of gout, as rapid absorption and a short half-life may help to
      avoid accumulation in patients with subclinical renal function impairment.
      Comorbidities should always be kept in mind when prescribing NSAIDs. Patients
      with previous or recent gastrointestinal bleeding, those receiving anticoagulant
      therapy or with haemorrhage diathesis, and those with renal insufficiency are at
      risk of developing severe adverse effects from NSAID administration.
      Corticosteroids are probably a reasonable choice for patients in whom colchicine
      and NSAIDs may be hazardous or for those with a history of previous intolerance
      to these drugs. Few trials using prednisone, prednisolone or triamcinolone
      acetonide are available, and dosages are prescribed following empirical data.
      Corticotropin has also been used to treat acute gout. Although it has been proven
      to be as effective as other corticosteroids or indomethacin, the need for
      multiple doses, parenteral administration and the high cost are major limitations
      for its use. Currently, the choice of a drug for the treatment of acute gout will
      depend on the balance between its efficacy and the potential adverse effects in a
      particular patient.

PMID- 18034549
TI  - Management of the patient with severe refractory rheumatoid arthritis: are the
      newer treatment options worth considering?
AB  - Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease leading
      to joint destruction. It is the most common cause of potentially treatable
      disabilities. The outcome of the disease varies from very mild to a refractory,
      rapidly progressive type with a high mortality rate. In recent years, profound
      changes in the traditional paradigms of RA therapy have been introduced. Instead
      of a therapeutically progressive approach, aggressive therapy is recommended for
      aggressive forms of RA. It has forced us to remodel the traditional treatment
      pyramid, and to start new strategies such as saw-tooth or step-down-bridge
      schedules. The last 10 years have seen wide acceptance of immunosuppressive
      therapy. These agents hold much promise for the further treatment of RA. A few
      years ago it seemed that we would be unable to influence the long term outcome in
      RA, but today the development of new drugs and techniques has increased our
      chances of fighting RA, and prospects for the future are even more promising.

PMID- 18034550
TI  - 111In-capromab pendetide: the evolution of prostate specific membrane antigen and
      the nuclear imaging of its 111In-labelled murine antibody in the evaluation of
      prostate cancer.
AB  - Each year, approximately 210,000 American men are diagnosed with prostate cancer
      and 41,800 die from the disease - numbers roughly equal to the incidence and
      mortality for breast cancer in women. Prostate cancer usually shows no symptoms
      in early stages, when it is most treatable. To detect the disease early,
      physicians usually recommend that every man 50 years and older have an annual
      examination consisting of a digital rectal examination and a prostate specific
      antigen (PSA) blood test. Conventional treatments such as surgical removal of the
      diseased prostate, external beam radiation, radioactive seed therapy and hormonal
      and/or chemotherapy treatment regimens are most successful for early stage
      prostate cancer and have limited effectiveness in advanced stages of the disease.
      For this reason, accurate staging of primary and recurrent prostate cancer is
      mandatory for proper therapeutic decisions. Nuclear medicine imaging of prostate
      cancer using the radiolabelled monoclonal antibody, (111)In-capromab pendetide,
      has proven useful in newly diagnosed patients with biopsy-proven prostate cancer
      in which there is high suspicion of distant metastatic disease and for
      prostatectomy patients with rising PSA levels and/or suspicion of recurrence or
      metastatic disease. Although not intended as a screening tool, it is used in
      conjunction with standard evaluation procedures for improved staging of patients.
      The monoclonal antibody, designated 7E11-C5, binds the prostate specific membrane
      antigen (PSMA) expressed on the surface of prostate epithelial cells and up
      regulated in tumour cells. The sensitivity and specificity for prostate cancer
      involved lymph node detection has been reported as 62 to 75% and 72 to 86%,
      respectively, compared with sensitivities of 4% and 15% for computerised
      tomography and magnetic resonance imaging. (111)In-capromab pendetide imaging has
      proven to be an accurate, non-invasive tool for detecting and staging sites of
      recurrence in the post-prostatectomy patient as well as metastatic sites in the
      patient with newly diagnosed prostate cancer.

PMID- 18034551
TI  - A role for interferon-beta in Guillain-Barre Syndrome?
AB  - Guillain-Barre syndrome (GBS) is an acute inflammatory demyelinating neuropathy
      that is associated with long-lasting morbidity and a substantial risk of
      mortality. The 2 reference treatments, plasma exchange and intravenous
      immunoglobulins (IVIg), do not change the functional prognosis for the most
      severely ill patients. The pathogenesis of GBS involves humoral and cellular
      immune dysfunctions that have only recently been characterised. Antibodies to
      nerve antigens may participate in complement activation, antibody-dependent
      macrophage cytotoxicity and reversible conduction failure. The cellular immune
      reaction is associated with increases in pro-inflammatory cytokines [such as
      tumour necrosis factor-alpha (TNFalpha)] and matrix metalloproteinases (MMPs;
      e.g. MMP-9), and a decrease in anti-inflammatory cytokines [such as transforming
      growth factor-beta1 (TGFbeta1)]. All the changes favour adhesion to and
      transmigration across the endothelium of immune cells, a key phenomenon
      associated with GBS. Recovery from GBS is characterised by the normalisation of
      these changes. Experimental allergic neuritis (EAN), the experimental model of
      GBS, has strikingly similar immunological characteristics. The usual treatment
      options for patients with GBS (plasma exchange and IVIg) mainly target the
      humoral component of the immune response. Interferon-beta (IFNbeta) is a cellular
      immunomodulator that inhibits antigen presentation and TNFalpha production and
      binding, and modulates macrophage properties. IFNbeta increases anti-inflammatory
      T cell functions and the production of anti-inflammatory cytokines, such as
      TGFbeta1. IFNbeta has important effects on leukodiapedesis, caused by modulating
      the expression of cell adhesion molecules and the MMP-9 proteinases. It has been
      used with success in EAN, in some patients with acute exacerbation of chronic
      inflammatory demyelinating polyneuropathy, and in 1 patient with GBS. The
      pathophysiology of patients with GBS, an understanding of IFNbeta properties and
      results of experimental studies support the investigation of IFNbeta in trials of
      patients with GBS.

PMID- 18034552
TI  - Therapeutic angiogenesis: potential role of basic fibroblast growth factor in
      patients with severe ischaemic heart disease.
AB  - Therapeutic angiogenesis is a rapidly evolving approach to the treatment of
      advanced coronary disease. The availability of growth factors such as basic
      fibroblast growth factor (bFGF or FGF2) has made possible the practical clinical
      application of this research. In this article, we summarise the basic biology of
      bFGF, a prototypical angiogenic growth factor, and the preclinical studies with
      this growth factor, and analyse recent clinical experience. While much remains to
      be learned, bFGF has been clearly shown to induce effective growth of new
      vasculature in a variety of animal models. The initial clinical data are
      promising, with patients demonstrating improvement in symptoms, quality of life
      and exercise tolerance. At the same time, the adverse effects profile has, to
      date, remained relatively benign.

PMID- 18034553
TI  - Platelet-activating factor antagonists: current status in asthma.
AB  - Platelet-activating factor (PAF) is a potent lipid-derived mediator of
      inflammation that is considered to have a potential role in the pathogenesis of
      asthma. PAF is produced by many cells associated with asthmatic inflammation and
      has the ability to evoke some of the clinical hallmarks of asthma, such as
      bronchoconstriction, mucus production and airway hyperresponsiveness (AHR). In
      addition, PAF has profound chemoattractant properties for eosinophils and
      neutrophils and it promotes an increase in microvascular permeability and oedema
      formation within the airways. Nevertheless, the definitive role of PAF in asthma
      remains elusive. PAF is formed as a result of the action of phospholipase A(2)
      and acetyltransferase on membrane phospholipids and it is degraded by a PAF
      specific acetylhydrolase. The biological effects of PAF are mediated by the
      activation of specific receptors expressed on effector cell surfaces, although
      intracellular signalling and paracrine actions have been described. In addition,
      at least part of the pulmonary effects of PAF could be related to the secondary
      release of leukotrienes. In the clinical setting, different ways of modifying the
      activity of PAF have been explored, in particular the inhibitory actions of PAF
      receptor antagonists. Both natural and synthetic PAF receptor antagonists have
      shown conflicting results. Although second generation PAF antagonists (apafant,
      UK-74505, SR-27417A) appear to have a good protective effect against the systemic
      and pulmonary actions of inhaled PAF, the protective effects of these compounds
      on allergen-induced responses and AHR are more modest. In the treatment of
      asthma, PAF receptor antagonists have failed to produce a significant impact in
      either acute asthma attacks or the maintenance therapy of chronic forms. Other
      pharmacological interventions of proven efficacy in asthma, such as salbutamol or
      5-lipoxygenase antagonists, have shown some anti-PAF effects. Whether the overall
      negative results with PAF receptor antagonists indicate that extracellular PAF is
      not a relevant mediator of airway inflammation or that the compounds explored are
      not capable of blocking the paracrine actions of PAF remains speculative. A PAF
      synthase inhibitor could be valuable in the elucidation of the role of PAF and it
      might be a promising and useful complementary therapeutic tool in the future.

PMID- 18034554
TI  - Long term management of liver transplant rejection in children.
AB  - The current management of hepatic allograft rejection after liver transplantation
      in children requires effective baseline immunosuppression to prevent rejection
      and rapid diagnosis and treatment to manage acute rejection episodes. The
      subsequent impact on chronic rejection is dependent on the combination of
      adequate prevention and the treatment of acute rejection. Tacrolimus is a
      macrolide lactone that inhibits the signal transduction of interleukin-2 (IL-2)
      via calcineurin inhibition. Introduced in 1989, tacrolimus was first used in the
      salvage of refractory acute or chronic rejection under cyclosporin or to rescue
      patients with significant cyclosporin-related complications. The majority of
      paediatric transplant centres use a combination of steroids with tacrolimus as a
      basic immunosuppressant regimen following paediatric liver transplantation. This
      combination has allowed the acute cellular rejection-free rate to increase to
      between 30 and 60%, while lowering the rate of refractory rejection to less than
      5%. Corticosteroid-resistant rejection is commonly treated with monoclonal
      (muromonab CD3) or polyclonal preparations. Although most episodes of acute
      cellular rejection occur during the first 6 weeks after liver transplant, the
      appearance of late acute liver allograft rejection must raise the question of
      noncompliance, especially in the adolescent population. Chronic rejection is
      becoming increasingly rare under tacrolimus-based immunosuppression. Tacrolimus
      is effective in reversing refractory acute cellular rejection or early chronic
      rejection in patients initially treated with cyclosporin-based regimens. Patients
      with a history of noncompliance as well as children with autoimmune liver disease
      are at risk of chronic rejection. Retransplantation therapy for chronic rejection
      has, fortunately, become more rare in the tacrolimus era with only 3% of
      retransplants being performed for this indication. Newer immunosuppressive agents
      are further modifying the long term management of liver allograft rejection.
      These include mycophenolate mofetil, rapamycin and IL-2 antibodies such as
      daclizumab. The development of these agents is allowing patient-specific
      immunosuppressive management to minimise rejection as well as the complications
      related to immunosuppression.

PMID- 18034555
TI  - Varicella vaccination in children.
AB  - Varicella vaccines have been developed, studied, tested and used since the early
      1970s, first in Japan and subsequently in Europe, the US, Asia and South and
      Central America. Varicella vaccination was first used to immunise Japanese
      children in cancer remission, as wild-type varicella disease is often fatal in
      immunocompromised individuals. Since then, it has been licensed for use in
      healthy children as well. There are 3 manufacturers of the vaccine: Biken
      (Japan), Merck and Co. (US) and SmithKline Beecham (Belgium). The Biken vaccine
      has been approved for use in Japan since 1986 (although it was developed and used
      for research purposes from 1974). The Merck and Co. vaccine was approved in the
      US in March 1995 and the SmithKline Beecham vaccine was first licensed for use in
      immunocompromised children in 1984 and for healthy children in Sweden in October
      1994. All 3 vaccines are derived from the Oka (Japanese) strain obtained from an
      immunologically normal 3-year-old Japanese boy named Oka with wild-type disease.
      Aventis-Pasteur has also purchased the rights to the Oka strain but no published
      literature is available for review. Use of the varicella vaccine has been
      controversial because many argue that: (i) the disease is mild and not worth
      preventing; (ii) the long term immunity provided by the vaccine is unknown; and
      (iii) the average age of those with the disease will increase if the vaccine is
      used and hence there will be more complications in older patients and, therefore,
      more costs. Because of some outbreaks of secondary bacterial infections after
      varicella in children in US day care centres, vaccination of healthy children is
      required in some states. It will be interesting to see whether other countries
      adopt a similar recommendation as more families have 2 working parents. The
      financial benefit of the vaccine (keeping parents at work) may encourage more use
      of the vaccine and a subsequent recommendation for immunisation schedules.

PMID- 18034556
TI  - Adjuvanted influenza vaccine.
AB  - Adjuvanted influenza vaccine is composed of 2 type A and 1 type B inactivated
      influenza subunits combined with an oil-and-water emulsion (MF59). Each dose
      contains 15microg haemagglutinin per strain. Adjuvanted influenza vaccine was
      immunogenic in elderly vaccinees and in younger adults after 1 to 3 consecutive
      annual injections. According to studies available to date, the adjuvanted vaccine
      was more immunogenic than the nonadjuvanted subunit or split virus vaccines and
      the virosomal vaccine for 1 to 3 of the 3 strains tested per injection. The
      immunogenic effect generally persisted for longer after the adjuvanted vaccine
      than the nonadjuvanted subunit vaccine in elderly recipients. The adjuvanted
      vaccine also appeared to be more effective than the nonadjuvanted subunit vaccine
      against antigenically different heterovariant strains in elderly vaccinees. The
      28-day seroprotection rate in 4 studies was significantly greater after the
      adjuvanted vaccine for 1 or 2 of the 3 strains tested compared with the
      nonadjuvanted subunit vaccine and the virosomal vaccine and for 1 of 3 strains
      compared with the split virus vaccine. The incidence of systemic adverse events
      was generally low. Local reactions such as pain, erythema and induration occurred
      more frequently with the adjuvanted than the 2 nonadjuvanted or the virosomal
      vaccines; however, these were mild and transient.

PMID- 18034557
TI  - Adjuvanted influenza vaccine: a viewpoint by C. L. Park.

PMID- 18034558
TI  - Adjuvanted influenza vaccine: a viewpoint by R. Baltussen.

PMID- 18034559
TI  - ACE gene polymorphism and diabetic complications: is there a connection?
AB  - The insertion/deletion (I/D) polymorphism of the ACE gene accounts for 50% of the
      variation in serum ACE levels and activity. However, its functional significance
      with regard to diabetic complications and cardiovascular disease remains
      controversial. To review the literature assessing the significance of ACE gene
      polymorphism on the initiation and progression of diabetic complications and
      treatment implications, a systematic review of the Medline, Pubmed and EMBASE
      databases was performed. Keywords were 'diabetes mellitus', 'diabetic
      nephropathy', 'ACE gene polymorphism' and 'genotype', for the period 1966 to
      August 1999. Overall, ACE gene polymorphism appears to affect the progression of
      diabetic nephropathy, with individuals homozygous for the deletion allele (DD)
      having a shorter time period from the onset of microalbuminuria to renal
      replacement therapy and decreased survival thereafter. This may reflect relative
      resistance to ACE inhibitor therapy. There is no association between ACE gene
      polymorphism and retinopathy. Further large prospective studies are required to
      clarify the association of ACE gene polymorphism and diabetic complications.
      However, it appears that the deletion allele acts in a co-dominant manner as a
      susceptibility factor in the progression of diabetic nephropathy. ACE genotyping
      may therefore provide a simple method of identifying high risk individuals and
      allow the implementation of early and aggressive therapy.

PMID- 18034560
TI  - Potential of recombinant human growth hormone in HIV-associated adipose
      redistribution syndrome.
AB  - HIV infection recently has been complicated by the emergence of a rare metabolic
      dysmorphic disorder characterised by fat atrophy, redistribution and accumulation
      in the setting of hyperlipidaemia and, on occasion, hyperglycaemia. The disorder,
      sometimes referred to as HIV-associated Adipose Redistribution Syndrome (HARS),
      has a prevalence rate of about 50 to 60% and seems temporally related to the
      advent of highly active antiretroviral therapy, especially the usage of protease
      inhibitors. Various studies also implicate the nucleoside analogues stavudine,
      didanosine and lamivudine in the pathogenesis of HARS, especially fat atrophy. It
      is uncertain whether the changes described in HARS represent a single syndrome or
      a group of related syndromes. Reports have noted differences between morphologic
      and metabolic changes. More recently, it has been suggested that fat atrophy and
      fat accumulation may also be separate entities. There are several potential
      pathogenic theories for HARS that implicate both protease inhibitors and
      nucleoside analogues as causative agents. However, long term HIV infection rather
      than any specific agent or class of agent may be the source. Recombinant human
      growth hormone (rhGH) is a mammalian cell-derived product, which has been useful
      in a variety of human disorders ranging from pituitary dwarfism to septic shock.
      It has anabolic, immunological and metabolic properties that restore normal
      functioning to many aberrant disease pathways. The lipolytic properties of rhGH
      have been especially beneficial in the diminution of localised fat accumulation
      in the dorsocervical area (buffalo humps) and truncal region. This has been
      observed in various reports where rhGH has been administered at doses of 5 to 6
      mg/day in patients with HARS for periods ranging from 3 months to >2 years.
      Relapses after discontinuation of rhGH occurred in most patients. Adverse effects
      included carpal tunnel syndrome, facial swelling, arthralgias and myalgias and
      worsening or onset of hyperglycaemia. The small uncontrolled studies conducted to
      date suggest that the most notable effect of rhGH treatment is the reduction of
      truncal adiposity and buffalo humps and that the agent has little effect on
      restoring the adiposity of the appendicular muscles, buttocks or face. Although
      most patients with HARS have associated hyperlipidaemia, rhGH has no notable
      effect on serum cholesterol and triglyceride levels. However, blood glucose
      levels can increase and pre-existent diabetes mellitus may worsen. A short term
      confirmatory placebo-controlled trial in patients with HARS is urgently needed,
      as are comparative trials using other anabolic agents such as oxandrolone and
      testosterone.

PMID- 18034561
TI  - Juvenile idiopathic arthritis: will etanercept be an improvement over current
      therapies?
AB  - Overexpression of cytokines in inflamed joints plays an important role in joint
      inflammation and in damage to articular tissue. Biological agents aimed at
      specifically antagonising tumour necrosis factor (TNF) are effective in the
      treatment of adult rheumatoid arthritis. A recent trial of etanercept, a
      genetically engineered fusion protein consisting of the Fc domain of human IgG1
      and the TNF receptor p75, has demonstrated that this agent is also well tolerated
      and effective in patients with juvenile idiopathic arthritis (JIA). Etanercept
      offers a promising new alternative for patients with JIA who have persistently
      active arthritis despite treatment with methotrexate. Further studies are needed
      to clarify whether etanercept is equally effective in the various onset types of
      JIA (oligoarthritis, polyarthritis and systemic arthritis), whether it can modify
      disease progression and whether it can be administered safely for long periods of
      time to children.

PMID- 18034562
TI  - Practical steps in the diagnosis and management of gout.
AB  - One of the earliest described conditions, gout continues to plague humanity. It
      is characterised by the deposition of monosodium urate crystals in the joints and
      soft tissue. The main clinical features of gout are hyperuricaemia, acute
      monoarticular arthritis, tophi and chronic arthritis, along with nephrolithiasis.
      Gout typically occurs in middle age and more commonly in men. Asymptomatic
      hyperuricaemia does not require treatment. The initial attack of acute gout
      usually affects a single joint, often the first metatarsal phalangeal joint.
      Definitive diagnosis requires demonstration of urate crystals in the joint fluid.
      Treatment of acute gout includes nonsteroidal anti-inflammatory drugs (NSAIDs),
      colchicine and corticosteroids. The most important factor in success of treatment
      is how quickly therapy is begun after onset of symptoms. Drug treatment of
      hyperuricaemia includes allopurinol, sulfinpyrazone, probenecid and benzbromarone
      and should be used in patients with frequent gout attacks, tophi or urate
      nephropathy.

PMID- 18034563
TI  - Heparin-induced thrombocytopenia: recommendations for optimal use of recombinant
      hirudin.
AB  - Recombinant hirudins have a definite role in the treatment of patients with
      heparin-induced thrombocytopenia (HIT). The most important adverse effects are
      haemorrhages and the induction of antihirudin antibodies. Major haemorrhages were
      not significantly increased in patients with HIT compared with a historical
      control group, but prospective data comparing hirudin and heparinoids such as
      danaparoid are lacking. The definition of the optimal method for monitoring and
      the availability of an antidote for hirudin would probably increase safety with
      this drug. To date, haemofiltration using high-flux filter systems is the only
      way to remove an overdosage of hirudin from the circulation. In patients with
      renal impairment requiring hirudin treatment, it therefore seems safer to start
      with a low dose that is subsequently adjusted according to the activated partial
      prothromboplastin time or ecarin clotting time. Even in special circumstances,
      such as cardiopulmonary bypass or dialysis, hirudins can be applied successfully
      if care is taken to monitor their effects meticulously. There are many other
      indications in which hirudins have shown feasibility (e.g. acute coronary
      syndromes) but available data preclude definite conclusions.

PMID- 18034564
TI  - Photodynamic therapy in immune (non-oncological) disorders: focus on
      benzoporphyrin derivatives.
AB  - This review examines the efficacy of photodynamic therapy in the treatment of
      immunological disorders. Photodynamic therapy (PDT) is a 2-step procedure.
      Firstly, a photosensitiser is introduced into the body, where it accumulates
      selectively in cells with elevated metabolism, such as cancer cells or activated
      cells of the immune system. Second, light is applied at a wavelength that excites
      the photosensitiser, producing a variety of short-lived oxygen-derived species.
      The effect is dependent on the doses of both photosensitiser and activating
      light. The mechanisms of action of PDT are multifactorial. Induction of high
      levels of oxidative stress results in necrotic cell death, while lower intensity
      oxidative stress initiates apoptosis. Sublethal doses may result in the
      modification of cell surface receptor expression levels and cytokine release and
      consequently influence cell behaviour. Immunomodulatory PDT (IPDT) utilises
      mainly apoptotic and sublethal doses. The studies reported here utilise
      verteporfin, a benzoporphyrin-derived chlorin-like photosensitiser. Veteporfin is
      a second generation photosensitiser, displaying rapid clearance and consequently
      a reduced period of skin photosensitivity compared with the first generation
      photosensitiser, porfimer sodium. In vivo studies showed that IPDT was effective
      in alleviating immunopathology in murine models of arthritis, contact
      hypersensitivity, experimental allergic encephalomyelitis and retention of
      allogeneic skin grafts. Based on these findings, early stage clinical trials with
      IPDT were initiated recently for the treatment of psoriasis, psoriatic arthritis
      and rheumatoid arthritis. While verteporfin has been the photosensitiser which
      pioneered IPDT, a new benzoporphyrin derivative photosensitiser, QLT0074, is
      under development. This has demonstrated an enhanced avidity for target cells as
      well as improved clearance characteristics.

PMID- 18034565
TI  - Efficacy of interferon-based therapy in the treatment of thalassaemic patients
      with chronic hepatitis C: a meta-analysis.
AB  - OBJECTIVE: To identify the interferon-alpha (IFNalpha) treatment protocol most
      suitable for patients with thalassaemia major who have chronic hepatitis C.
      DESIGN AND SETTING: This was a meta-analysis of studies in the international
      literature between 1990 and 1999. METHODS: Studies were identified from a search
      of Medline and Embase, and analysed by the Mantel-Haenszel-Peto statistical
      method. RESULTS: We identified 6 nonrandomised trials, 2 of which were
      controlled, that treated a total of 201 patients. Most studies used the lowest
      dose level (3 MIU/m(2)), all used a thrice-weekly regimen, and most used IFNalpha
      2b, although the use of natural IFNalpha did not induce production of anti
      interferon antibodies. The best sustained response and remission rates tended to
      be achieved with higher doses and longer cycles of IFNalpha. CONCLUSIONS: The
      best interferon-based therapy to treat polytransfused thalassaemic patients with
      chronic hepatitis C is represented by the use of natural IFNalpha or IFNalpha-2b,
      initially at high dosages (5 to 10 MIU/m(2) 3 times weekly) for 6 months,
      followed by lower dosages (3 MIU/m(2) 3 times weekly) for a further 6 to 9
      months.

PMID- 18034566
TI  - Reporting adverse events in gene therapy studies.
AB  - The reporting of adverse events occurring in gene therapy studies is currently
      under discussion. There are many agencies involved in the reporting of adverse
      events, often with reporting guidelines that are unique to each organisation.
      Guidelines differ according to the type of event (adverse event, adverse drug
      reaction, unexpected adverse drug reaction, serious adverse event and serious
      adverse drug reaction). While there is a move toward making guidelines more
      stringent in the US, there is concern that this will increase the number of
      reports of unrelated events, create confusion from a global perspective, and
      increase public concern needlessly.

PMID- 18034567
TI  - Hyperimmune products in the prevention and therapy of infectious disease: a
      report of a hyperimmune products expert advisory panel.
AB  - This paper reviews a meeting at which basic pathophysiology of infections,
      mechanisms of action of hyperimmune products and pharmacokinetic and
      pharmacodynamic parameters, as well as currently available hyperimmunes and their
      potential new targets and uses, were discussed. A hyperimmune product was defined
      as either a monoclonal antibody or a polyclonal preparation enriched with
      antibody directed against one or more particular targets. A number of issues were
      emphasised, including: resistant bacterial pathogens, such as Staphylococcus
      aureus and Streptococcus pyogenes; the role of hyperimmune intravenous globulins
      in the prevention of sepsis in low birthweight infants; hepatitis B virus
      infection associated with liver transplantation; combination therapy; the
      potential role of hyperimmunes in the prevention and treatment of hepatitis C
      virus; and the use of immunoglobulins for the prophylaxis of Epstein-Barr virus
      related lymphoproliferative disease. Routes of administration were also
      discussed. It was concluded that the development of hyperimmunes faces numerous
      obstacles. It was agreed that the use of hyperimmunes in clinical trials must be
      standardised; clinical trials must be large enough to have sufficient power to
      demonstrate efficacy with clear-cut end-points, and means need to be developed,
      in conjunction with regulatory agencies, for the feasible evaluation of
      combination products. However, progress in all these aspects will provide a wide
      range of hyperimmunes for future use.

PMID- 18034568
TI  - Comparative tolerability of treatments for juvenile idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) includes several forms of chronic arthritis
      in children. Treatments are chosen according to the type and severity of the
      disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids remain
      the mainstays of therapy. Traditional slower acting anti-rheumatic drugs, such as
      gold therapy, penicillamine, sulfasalazine, tiopronin and hydroxychloroquine, are
      usually poorly active in children. In addition, adverse effects are common,
      including severe macrophage activation syndrome with gold therapy or
      sulfasalazine. Low dose, once weekly methotrexate has emerged as the therapeutic
      agent of choice for children who fail to respond adequately to the administration
      of an NSAID, especially in those with the extended oligoarticular subtype of the
      disease. Other immunosuppressive agents, such as cyclosporin, are sometimes
      combined with methotrexate. In recent years, novel treatments have been
      developed. Autologous hematopoietic stem cell transplantation is effective in a
      number of children with severe JIA, whose disease has been refractory to
      conventional therapy. However, only short term follow-up data are currently
      available for this novel therapy. In addition, severe infections complicated by
      macrophage activation syndrome and death have been reported. Finally, anti-tumour
      necrosis factor-alpha therapy has shown efficacy in more than two-thirds of
      children with JIA and polyarthritis, and other cytokine inhibitors may be soon
      available.

PMID- 18034569
TI  - Cyclosporin as baseline immunosuppression in solid organ transplantation.
AB  - Cyclosporin is currently the basis of most immunosuppressive protocols after
      solid organ transplantation. In recent years a variety of new substances, such as
      tacrolimus, mycophenolate mofetil, sirolimus and everolimus (SDZ-RAD) have been
      developed. Besides these new immunosuppressants, which are structurally unrelated
      to cyclosporin, new formulations of cyclosporin have been introduced into the
      market. This review is intended to summarise the current knowledge on the use of
      cyclosporin as baseline immunosuppression after solid organ transplantation.
      Special emphasis is placed on comparison of cyclosporin-based immunosuppression
      with that by other recently introduced drugs that can be used as baseline
      immunosuppressants. Furthermore, the different formulations of cyclosporin are
      compared with each other. Finally, the optimal use of cyclosporin as baseline
      immunosuppressant in the early postoperative course as well as during long term
      immunosuppression is discussed from a practical perspective. During the past
      years a number of galenic formulations of cyclosporin with pharmacokinetic
      characteristics comparable to that of cyclosporin-modified-Novartis (Neoral) have
      been developed. Some data on oral resorption are available for the new
      formulations. So far, however, only healthy volunteers or patients stable after
      kidney or liver transplantation have been investigated in clinical trials using
      these new formulations. Definite data on the resorption characteristics of the
      new galenic formulations of cyclosporin will come from the analysis of patients
      with liver transplants during the early post-transplant course receiving either
      cyclosporin-modified-Novartis or the new cyclosporin formulations.

PMID- 18034570
TI  - 131I tositumomab.
AB  - black triangle (131)I tositumomab is a radiolabelled murine anti-CD20 monoclonal
      antibody that binds specifically to the CD20 antigen on normal and malignant B
      lymphocytes. It has antitumour activity as a result of emission of beta
      particles, and activation of antibody-dependent cellular and complement-mediated
      cytotoxicity. black triangle (131)I tositumomab monotherapy consistently produced
      objective response rates of >or=60% in patients with relapsed or refractory, low
      grade or transformed low grade non-Hodgkin's lymphoma (NHL) in clinical trials.
      62% of patients responded to retreatment in 1 small trial. black triangle In 2
      studies, objective and complete response rates were higher and overall durations
      of response were significantly longer in patients treated with (131)I tositumomab
      compared with their last chemotherapy regimen. black triangle High dose (131)I
      tositumomab combined with autologous stem cell transplant produced an objective
      response rate of 86% in relapsed or refractory patients. black triangle (131)I
      tositumomab alone or in combination with fludarabine achieved an objective
      response rate of 100% in 2 preliminary reports in patients with previously
      untreated NHL. black triangle The dose-limiting toxicity of (131)I tositumomab is
      reversible myelosuppression, with approximately 18% of patients requiring
      haematological support in combined trial data. Other nonhaematological toxicities
      occur in approximately 20 to 40% of patients and include mild to moderate flu
      like symptoms.

PMID- 18034572
TI  - 131I tositumomab: a viewpoint by Wolfgang Kern.

PMID- 18034571
TI  - 131I tositumomab: a viewpoint by Michael L. Grossbard.

PMID- 18034573
TI  - Rotavirus vaccine: current status and future prospects.
AB  - Rotavirus is the most important cause of severe gastroenteritis in infants and
      children worldwide. Efforts to develop a vaccine have concentrated on live oral
      vaccines, especially with attenuated animal viruses. Because studies with rhesus
      monkey rotavirus and bovine rotavirus RIT 4237 or WC3 were inconsistent,
      reassortant rhesus and bovine vaccines have been developed that include the gene
      encoding the neutralising protein, VP7, of several human strains. These efforts
      culminated in the licensure of a tetravalent rhesus rotavirus vaccine, in 1998.
      Subsequent reports linking vaccination to intussusception, however, led to
      withdrawal of this vaccine. Trials, nevertheless, continue with an oral bovine
      reassortant vaccine and an attenuated human strain, 89-12. Other strategies in
      preclinical development include the use of virus-like particles, DNA vaccines and
      subunit vaccines given by mucosal and nonmucosal routes.

PMID- 18034574
TI  - Chronic rejection of the liver: the role of immunosuppression.
AB  - Liver transplantation is now widely recognised as an effective treatment option
      for patients with advanced liver disease. Many units now achieve greater than 85%
      survival at 1 year, with the majority of patients having a high quality of life.
      The maintenance of a high quality of life requires careful clinical management to
      ensure that the continued maintenance of excellent liver graft function is not
      achieved at the expense of immunosuppressive drug complications or morbidity.
      Acute liver rejection will occur in between 30 to 45% of patients, although with
      modern immunosuppressive protocols, usually combining one of the calcineurin
      agents, either cyclosporin or tacrolimus, with both azathioprine and
      corticosteroids (prednisolone) ensures that relatively few grafts are lost from
      severe acute rejection. While the incidence and severity of acute rejection may
      be one factor in raising the risk of chronic rejection, it may not be the
      principal one in many patients. It is important to recognise that the frequency
      of rejection also varies with the primary underlying liver disease, with patients
      with hepatitis B or alcoholic liver disease having relatively low rejection
      rates, compared with patients with primary biliary cirrhosis (PBC) or primary
      sclerosing cholangitis (PSC), which range between 20 to 70%. Chronic rejection
      will account for some 5% of grafts lost in the first 3 to 5 years. Indeed, there
      is some evidence that the incidence of chronic rejection is actually declining
      over the past few years. While the reason for this apparent decline is uncertain,
      and it could relate to better immunosuppression management, or more likely to the
      growing recognition that chronic graft dysfunction may be due to recurrent liver
      disease, such as autoimmune hepatitis, PBC, PSC, or recurrent hepatitis C. The
      differentiation of recurrent primary liver disease from chronic rejection can
      prove to be very difficult in clinical practice. Thus, the clinician must
      carefully monitor liver and graft function, evaluate any biochemical changes, and
      try to reach a clear diagnosis before considering any modification of
      immunosuppressive schedules.

PMID- 18034575
TI  - Interleukin-2 in cancer therapy: uses and optimum management of adverse effects.
AB  - Recombinant interleukin-2 (rIL-2) produces remissions in several human tumours,
      including metastatic renal cell cancer (RCC) and malignant melanoma. High-dose
      intravenous bolus rIL-2 is approved in the US in these 2 indications, based on
      evidence of rIL-2-induced durable remissions in a significant minority of
      patients. Due to the toxicity associated with high-dose rIL-2, alternative
      regimens were investigated in RCC, including low-dose intravenous bolus,
      subcutaneous outpatient regimens and continuous intravenous infusion, yielding
      similar response rates. A prospective randomised trial comparing different doses
      and routes of administration is underway. Because response rates to single agent
      rIL-2 are inadequate, combination therapies were studied. In RCC patients, a
      combination of rIL-2 and IFNalpha resulted in better response rates than either
      cytokine alone, with no apparent survival advantage. Combination with
      chemotherapy increased toxicity and had no proven benefit. Results of adoptive
      immunotherapy studies combining rIL-2 with either lymphokine-activated killer
      cells or tumour infiltrating lymphocytes were comparable to those of rIL-2 alone.
      In malignant melanoma, combination therapy of rIL-2 with chemotherapy was
      explored. Results of single-institution phase II combination studies of variable
      chemotherapy and rIL-2 and IFNalpha regimens were promising and randomised trials
      are underway. rIL-2 is being is evaluated in haematological malignancies. The
      rationale is based on pre-clinical evidence that a variety of leukaemic blasts
      are sensitive to cytolysis or growth inhibition mediated by rIL-2-activated
      immune effector cells. New immunotherapeutic strategies may ultimately improve
      the anti-tumour efficacy of rIL-2-based therapy. Early trials using rIL-2 as
      adjuvant therapy to vaccines or dendritic cell-based therapy have yielded
      promising results. rIL-2 therapy initiates a cytokine-mediated pro-inflammatory
      process leading to an adverse effect profile that is quite different from
      traditional chemotherapeutic agents. Dose-limiting toxicities are primarily
      cardiovascular and pulmonary and are dose-dependent in frequency and severity.
      Patients receiving high-dose regimens may require intensive care unit support,
      limiting its use to those with excellent performance status and adequate organ
      function. Patients receiving less intensive dose regimens may require less
      rigorous screening and monitoring. It has been postulated that rIL-2 related
      toxicity is mediated through the release of secondary cytokines, including TNF,
      IFNgamma, IL-6 and IL-1. With the increasing understanding of the
      pathophysiological mechanisms of the effects of rIL-2, it is possible that
      concurrent administration of selective cytokine antagonists may reduce the
      toxicity associated with rIL-2 without interfering with its anti-neoplastic
      activity.

PMID- 18034576
TI  - Skin cancer risk associated with immunosuppressive therapy in organ transplant
      recipients: epidemiology and proposed mechanisms.
AB  - The aim of this review is to summarise the available literature regarding the
      epidemiology and proposed mechanisms of skin cancer development in organ
      transplant recipients who are receiving lifelong treatment with immunosuppressive
      therapy and to review the different strategies for managing complications in this
      group of patients. Organ transplantation is complicated by an increased incidence
      of certain cancers, of which non-Hodgkin's lymphoma, Kaposi's sarcoma and
      squamous cell carcinoma are the most common. The most important risk factor for
      these cancers is immunosuppressive therapy. The relative importance of different
      immunosuppressive therapy regimens in relation to the development of skin cancer
      is still unclear. Immunosuppression per se may play the most important role, but
      other mechanisms, which are independent of host immunity and which may be
      different for the various agents used, may also be of importance for the
      increased risk of cancer. Apart from immunosuppressive therapy, exposure to
      sunlight and infection with human papillomaviruses are believed to be the most
      important risk factors for the development of cutaneous squamous cell carcinoma
      in organ transplant recipients. Human papillomaviruses, no doubt, benefit
      considerably from immunosuppression, as is indicated by the large number of warts
      found in these patients, but many questions remain unanswered about their
      significance in cutaneous oncogenesis. The E6 protein from a range of cutaneous
      human papillomavirus types effectively inhibits apoptosis in response to
      ultraviolet light damage. It is, therefore, conceivable that the development of
      skin cancer in organ transplant recipients is the result of a complex interplay
      between exposure to ultraviolet radiation, human papillomavirus infection and
      genetic predisposition. Measures for protection from the sun are important for
      reducing the risk of skin cancer in organ transplant recipients. Regular
      surveillance of patients with skin problems and easy access to a dermatologist
      for these patients is advised. Changing the immunosuppressive regimen from
      azathioprine to cyclosporin or vice versa does not seem to relieve the skin
      problems. Tapering the immunosuppressive therapy to the lowest possible dose may
      be of some advantage. Oral retinoids, e.g. acitretin, have some effect in
      reducing the number of keratotic skin lesions and in the prevention of skin
      cancer in organ transplant recipients. Resurfacing the back of the hand can be a
      successful treatment for patients with multiple skin cancers on the back of the
      hand and can be used prophylactically in patients with severely actinically
      damaged skin.

PMID- 18034577
TI  - The cost of Crohn's disease: drugs or surgery?
AB  - New biological medical therapies and innovative surgical approaches have
      revolutionised the care of patients with Crohn's disease. Until these innovations
      began to be utilised over the past decade, studies of the economics of Crohn's
      disease care were relatively scarce. Questions from both clinical and economic
      standpoints now arise over potential choices between medical and surgical
      approaches to patients with Crohn's disease. Initial economic studies suggested
      that the vast majority of costs in Crohn's disease were due to inpatient services
      and surgery. The large variance in cost data between patients resulted in a very
      small percentage of patients accounting for a disproportionately large percentage
      of the overall costs, with the bulk of costs, charges and reimbursements accrued
      by surgical cases. Studies suggest that surgery would need to result in a
      decreased utilisation of outpatient services in order to be 'cost-effective'.
      Evaluation of the clinical course of Crohn's disease suggests that the surgically
      induced remission state is the longest remission state generally experienced by
      the patients, although sophisticated cost analysis fails to show enough of a
      remission benefit to offset the high costs associated with surgical procedures
      and post-operative convalescence. Bowel-sparing intestinal strictureplasty and
      minimally invasive laparoscopic surgeries have the potential to substantially
      decrease the costs associated with disease. These techniques need to be applied
      to a larger percentage of surgical Crohn's patients before the overall economic
      benefits can be fully assessed. Indirect costs and disability may account for
      most of the overall costs associated with Crohn's disease. Quality-of-life
      analyses have revealed that patients ill with Crohn's disease perform poorly, and
      the detrimental effects of medications or surgery may further increase disability
      in these patients. Future cost-utility studies may reveal the extent to which
      overall costs are affected by these issues. This review of the currently
      available literature on the economics of Crohn's disease suggests that medical
      therapy which can substantially reduce the utilisation of hospitalisations and
      surgery might be cost effective, even if the acquisition cost of the drug is
      high. However, broader application of specialised surgical techniques, together
      with the long post-operative remission state enjoyed by most Crohn's patients,
      may also offer a cost-effective long term approach to the disease. It is likely
      that both surgical and medical approaches will continue to be used in the
      treatment of Crohn's disease, with options for each patient being carefully
      considered on an individual basis.

PMID- 18034578
TI  - Is there a role for antibiotics in the treatment of asthma?: involvement of
      atypical organisms.
AB  - Emerging evidence suggests an association between some asthma and pulmonary
      infection by the atypical organisms Chlamydia pneumoniae and Mycoplasma
      pneumoniae, but a causal role for infection remains unproven and controversial.
      Most acute exacerbations of asthma are triggered by acute infections that are due
      to viral respiratory pathogens, not to bacteria or atypical organisms.
      Administration of antibiotics for acute exacerbations of asthma has been shown to
      be ineffective. Most evidence linking atypical infections to asthma is consistent
      with a promoting role for chronic infection in producing persistent asthma
      symptoms. Preliminary studies suggest that prolonged (>/=6 weeks) administration
      of doxycycline or macrolides may eradicate C. pneumoniae from respiratory
      secretions and improve long term, not acute, asthma symptoms. Randomised,
      controlled trials are currently under way to investigate the effectiveness of
      these prolonged courses of macrolides and azalides (roxithromycin, clarithromycin
      and azithromycin) in adults with stable persistent asthma. Traditional courses (7
      to 10 days) of any antibiotic are incapable of eradicating chronic C. pneumoniae
      or M. pneumoniae infection; furthermore, beta-lactam and sulphonamide-based
      antibiotics that are commonly prescribed in acute respiratory syndromes are
      ineffective against these atypical organisms. Unless the goal is to treat
      documented sinusitis associated with asthma, it is inappropriate to prescribe
      traditional courses of any antibiotic for acute asthma exacerbations; whether
      longer courses of antibiotics should be prescribed to eradicate chronic atypical
      infections and decrease persistent asthma severity remains to be established.

PMID- 18034579
TI  - Drug concentration monitoring of immunosuppressive agents: focus on tacrolimus,
      mycophenolate mofetil and sirolimus.
AB  - Several new immunosuppressive agents have recently been approved for use in solid
      organ transplantation. Many of these agents have narrow therapeutic ranges, which
      necessitates drug concentration monitoring in order to optimise efficacy,
      minimise toxicity and individualise dosages. Some of the lessons learned with the
      clinical use of the revolutionary agent cyclosporin have been applied to the
      newer agents tacrolimus and sirolimus. The agent mycophenolate mofetil has been
      in clinical use without widespread drug concentration monitoring; however, recent
      data suggest that therapeutic monitoring may improve clinical outcomes,
      especially in certain high risk subsets of patients. This review focuses on the
      literature published to date on drug concentration monitoring of the newer
      immunosuppressive agents - tacrolimus, mycophenolate mofetil and sirolimus. In
      addition, pertinent aspects of the clinical pharmacokinetics and metabolism of
      each agent are reviewed.

PMID- 18034580
TI  - Present and potential therapy for allergic rhinitis: a review.
AB  - Allergic rhinitis can affect up to one-fifth of the population and the economic
      impact is increasing. H(1) receptor antagonists were the first major
      pharmacologic treatment, but the associated sedation limited their use. The 2
      initial second generation less sedating antihistamines, astemizole and
      terfenadine, were found to prolong the cardiac QT(c) interval, especially when
      administered with other medications metabolised by the same cytochrome (CYP) P450
      isoenzyme, CYP3A4. Other second generation antihistamines, fexofenadine,
      loratadine and cetirizine, do not cause clinically significant cardiac QT(c)
      interval prolongation. Two newer agents, ebastine and mizolastine, are also
      effective in the treatment of allergic rhinitis. Ebastine, however, prolongs the
      cardiac QT(c) interval in laboratory animals and humans, the clinical
      significance of which is unknown. Desloratadine and norastemizole, metabolites of
      loratadine and astemizole, respectively, are 2 other second generation
      antihistamines found to be effective treatments for seasonal allergic rhinitis.
      Unlike their parent compounds, they do not prolong the cardiac QT(c) interval.
      All clinically available intranasal corticosteroids are effective in the
      treatment of allergic rhinitis, but studies to evaluate possible long term
      systemic adverse effects are limited. Mometasone furoate and fluticasone
      propionate have lower oral bioavailability compared with other corticosteroids
      that are given intranasally. This may be important, since it is likely that some
      of the intranasal corticosteroid is ingested. Two 1-year growth studies in
      children indicated that intranasal beclomethasone dipropionate given twice daily
      reduces growth velocity, whereas intranasal mometasone furoate given once daily
      in the morning does not. Other studies are needed. Most but not all studies have
      shown that leukotriene antagonists are effective in the treatment of allergic
      rhinitis. H(1) receptor antagonists are not very effective in reducing nasal
      congestion, but leukotriene antagonists do attenuate this symptom. Furthermore,
      one study demonstrates an additive benefit in treating allergic rhinitis with the
      combination of a H(1) receptor and leukotriene antagonist. Clinical trials have
      demonstrated that anti-immunoglobulin (Ig) E is effective in the treatment of
      seasonal allergic rhinitis when free IgE is reduced to <25 microg/L. The
      reduction of total IgE is dose dependent and subcutaneous and intravenous
      administration are both effective. Immunotherapy is also an effective treatment
      for allergic rhinitis. CpG oligonucleotides is a novel adjuvant for allergen
      immunotherapy. This adjuvant used in a murine model shifts the immune response
      away from the allergic or TH2 phenotype. Studies in humans have not been
      performed.

PMID- 18034581
TI  - Meta-analysis of published clinical trials of a ribosomal vaccine (ribomunyl) in
      prevention of respiratory infections.
AB  - OBJECTIVE: To perform a meta-analysis using data from all clinical trials and
      studies of a ribosomal vaccine (Ribomunyl((R))) in order to estimate its overall
      effect on the number of infections and antibacterial courses used per person.
      DESIGN AND SETTING: Meta-analysis of studies performed between 1985 and 1999 in 7
      European countries and also in Kazakhstan, Tunisia, Morocco and Argentina.
      PATIENTS AND PARTICIPANTS: Information from 14 213 adults and children. RESULTS:
      There were 9 randomised, double-blind, placebo-controlled studies, 3 randomised
      nonblind studies and 16 nonblind studies with no placebo arm in which the
      response to ribosomal vaccine was compared with historical information. The mean
      number of infections per person in a study period of 3 months using placebo was
      found to be 2.39 (standard error +/- 0.50), and in a study period of 6 months was
      3.35 (+/-0.41) infections. In both study periods, ribosomal vaccine use was
      associated with a reduction in the number of infections per person of 1.43 (+/
      0.26). In the study period, patients on placebo reported 3.02 (+/-0.44)
      antibacterial courses, whereas ribosomal vaccine was associated with a reduction
      of 1.32 (+/-0.42) antibacterial courses. CONCLUSIONS: In spite of variability in
      data quality, and the small sample size in some of the studies, we conclude that
      in patients with recurrent respiratory infections ribosomal vaccine significantly
      reduces both the number of infections and the number of antibacterial courses
      compared with placebo. This study is a strong and objective demonstration of the
      efficacy of ribosomal vaccine in limiting the number of otorhinolaryngological
      infections in children and adults.

PMID- 18034582
TI  - Sdz asm 981.
AB  - SDZ ASM 981 is an anti-inflammatory macrolactam which binds with high affinity to
      macrophilin-12. The resulting complex inhibits calcineurin, thus blocking the
      synthesis of inflammatory cytokines. Twice daily application of topical SDZ ASM
      981 1% cream was effective in the treatment of atopic dermatitis in adults and
      children in clinical trials. Summarised results from 260 patients with atopic
      dermatitis indicate that the efficacy of SDZ ASM 981 is dose dependent. The
      highest concentration evaluated (1% cream) was not as effective as betamethasone
      valerate 1% cream in this 3-week trial. The efficacy of SDZ ASM 981 and
      clobetasol ointments, used under occlusion, did not differ significantly in 10
      patients with chronic psoriasis. Likewise, SDZ ASM 981 0.6% and betamethasone
      valerate 1% creams were similarly effective in 66 patients with allergic contact
      dermatitis. Concentrations of SDZ ASM 981 in the blood during topical treatment
      were invariably below 2.1 microg/L. Oral SDZ ASM 981 20mg or 30mg twice daily
      were effective in a dose dependent manner in the reduction of psoriasis in adults
      with no evidence of adverse effects. SDZ ASM 981 was well tolerated in the
      available trials, exhibiting no potential for systemic adverse reactions and no
      atrophogenic potential, a problem commonly associated with corticosteroid
      treatment.

PMID- 18034583
TI  - SDZ ASM 981: a viewpoint by Jan D. Bos.

PMID- 18034584
TI  - SDZ ASM 981: a viewpoint by Ken Landow.

PMID- 18034585
TI  - Comment on "adjuvant therapy in pancreatic cancer: a critical appraisal".

PMID- 18034586
TI  - Comment on "adjuvant therapy in pancreatic cancer: a critical appraisal".

PMID- 18034588
TI  - Potential pharmacological interventions in polycystic kidney disease.
AB  - Polycystic kidney diseases (autosomal dominant and autosomal recessive) are
      progressive renal tubular cystic diseases, which are characterised by cyst
      expansion and loss of normal kidney structure and function. Autosomal dominant
      polycystic kidney disease (ADPKD) is the most common life- threatening,
      hereditary disease. ADPKD is more prevalent than Huntington's disease,
      haemophilia, sickle cell disease, cystic fibrosis, myotonic dystrophy and Down's
      syndrome combined. Early diagnosis and treatment of hypertension with inhibitors
      of the renin-angiotensin-aldosterone system (RAAS) and its potential protective
      effect on left ventricular hypertrophy has been one of the major therapeutic
      goals to decrease cardiac complications and contribute to improved prognosis of
      the disease. Advances in the understanding of the genetics, molecular biology and
      pathophysiology of the disease are likely to facilitate the improvement of
      treatments for these diseases. Developments in describing the role of
      intracellular calcium ([Ca(2+)](i)) and its correlation with cellular signalling
      systems, Ras/Raf/mitogen extracellular kinase (MEK)/extracellular signal
      regulated protein kinase (ERK), and interaction of these pathways with cyclic
      adenosine monophosphate (cAMP) levels, provide new insights on treatment
      strategies. Blocking the vasopressin V(2) receptor, a major adenylyl cyclase
      agonist, demonstrated significant improvements in inhibiting cytogenesis in
      animal models. Because of activation of the mammalian target of rapamycin (mTOR)
      pathway, the use of sirolimus (rapamycin) an mTOR inhibitor, markedly reduced
      cyst formation and decreased polycystic kidney size in several animal models.
      Caspase inhibitors have been shown to decrease cytogenesis and renal failure in
      rats with cystic disease. Cystic fluid secretion results in cyst enlargement and
      somatostatin analogues have been shown to decrease renal cyst progression in
      patients with ADPKD. The safety and efficacy of these classes of drugs provide
      potential interventions for experimental and clinical trials.

PMID- 18034589
TI  - Crohn's disease: a review of current treatment with a focus on biologics.
AB  - Crohn's disease is a debilitating and expensive disease that is growing in
      incidence in both developing and developed countries. While conventional
      therapies, such as corticosteroids and immunosuppressants, continue to play a
      vital role in treating this condition, it is evident that many affected
      individuals do not respond to therapy or develop intolerable adverse effects. The
      addition of modern biological therapies to the Crohn's disease armamentarium is
      providing a change in expectations for disease outcome. Infliximab and adalimumab
      are currently the only biological agents approved for induction and maintenance
      treatment in adults (infliximab and adalimumab) and children (infliximab) with
      Crohn's disease. Furthermore, infliximab has a beneficial effect on perianal
      fistulas. Other tumour necrosis factor (TNF)-alpha inhibitors, such as
      certolizumab pegol, also demonstrate promising results in adults with moderate to
      severe active disease. In addition, adalimumab and certolizumab pegol have shown
      clinical efficacy in patients who are intolerant to or lose response to
      infliximab, suggesting that switching between agents may allow response to be
      maintained over time. The primary safety concerns with TNFalpha inhibitors
      include increased risk of serious infection (including reactivation of
      tuberculosis), malignancy (particularly lymphoma) and demyelinating disease.
      Other agents in development include recombinant human anti-inflammatory
      cytokines, agents that target pro-inflammatory cytokines and granulocyte
      macrophage colony-stimulating factors. Further prospective studies will provide
      interesting insight into different mechanisms by which factors involved in the
      pathophysiology of Crohn's disease can be modulated.

PMID- 18034590
TI  - Pharmacotherapy for oesophagogastric cancer.
AB  - Gastric cancer is the seventh and oesophageal cancer the ninth most common cancer
      in the UK, and >50% of patients present with locally advanced or metastatic
      disease. The incidence of oesophageal and oesophagogastric junctional tumours is
      increasing, making these important disease entities to understand and research.
      Despite improvements in surgical and peri-operative supportive care, 3-year
      overall survival with surgery alone for resectable disease is still poor.
      Outcomes in localised oesophageal cancer are improved with pre-operative
      chemotherapy, and in gastric cancer with peri-operative treatment or post
      operative chemoradiotherapy. Oesophageal squamous cell carcinoma can be treated
      with definitive chemoradiotherapy as an alternative to surgery. While survival in
      patients presenting with metastatic disease is improved with the addition of
      systemic chemotherapy, median survival remains <1 year. Patients who are
      otherwise fit can be offered chemotherapy and this is superior to best supportive
      care. Regimens including a platinum and an anthracycline agent are favoured by
      the results of randomised trials. No standard second-line therapy has emerged.
      New research into taxanes has shown promising anti-cancer activity, and novel
      areas of investigation include incorporation of agents targeting vascular
      endothelial growth factor or epidermal growth factor receptor into standard
      regimens. This review focuses on the clinical trial evidence that dictates the
      optimal management of localised and advanced oesophagogastric cancer, focusing on
      pharmacotherapy. We examine areas of current research and highlight future
      therapeutic directions.

PMID- 18034591
TI  - Defining the role of insulin detemir in Basal insulin therapy.
AB  - Insulin detemir is a novel long-acting insulin analogue with a unique mechanism
      underlying its prolonged duration of action. Unlike neutral protamine Hagedorn
      (NPH) insulin (insulin suspension isophane) and insulin glargine, which
      precipitate after administration, insulin detemir remains soluble after it is
      injected. The prolonged duration of action of insulin detemir is a result of the
      ability to self-associate into hexamers and dihexamers, and to bind reversibly to
      albumin. This mechanism of protraction provides a more prolonged, consistent and
      predictable glycaemic effect in patients with type 1 or type 2 diabetes mellitus
      compared with NPH insulin. Clinical studies have demonstrated that insulin
      detemir administered once or twice daily is at least as effective as NPH insulin
      and insulin glargine in achieving glycaemic control. Most trials have also shown
      that insulin detemir exhibits less intrapatient variability in glycaemic control
      compared with NPH insulin and insulin glargine. One of the benefits of insulin
      detemir is its favourable effect on bodyweight. Insulin detemir has shown weight
      neutrality in patients with type 1 diabetes and is associated with less weight
      gain than NPH insulin in clinical studies. Patients with type 2 diabetes using
      insulin detemir gain less weight than patients using NPH insulin and insulin
      glargine. In addition, a reduced risk of hypoglycaemia, particularly nocturnal
      hypoglycaemia, has been reported with insulin detemir compared with NPH insulin
      in patients with type 1 and type 2 diabetes. A reduced risk of major and
      nocturnal hypoglycaemia compared with insulin glargine in patients with type 1
      diabetes has also been observed. Together, these data indicate that insulin
      detemir is a valuable new option for basal insulin therapy in patients with type
      1 or type 2 diabetes.

PMID- 18034592
TI  - Cetuximab: a review of its use in squamous cell carcinoma of the head and neck
      and metastatic colorectal cancer.
AB  - Cetuximab (Erbitux) is a human-mouse chimeric monoclonal antibody, which
      competitively binds to the accessible extracellular domain of the epidermal
      growth factor receptor (EGFR) to inhibit dimerisation and, subsequently, inhibit
      tumour growth and metastasis. In the EU and the US, cetuximab has been approved
      for use with concomitant radiotherapy in patients with locally advanced squamous
      cell carcinoma of the head and neck (SCCHN) and in combination with irinotecan
      for the treatment of metastatic colorectal cancer (mCRC) in patients with EGFR
      expressing tumours who are refractory to irinotecan-based therapy. In the US,
      cetuximab has also been approved as monotherapy in patients with recurrent or
      metastatic SCCHN for whom platinum-based therapy has failed and in patients with
      mCRC who are intolerant of irinotecan-based regimens.In treatment-naive patients
      with locoregionally advanced SCCHN, cetuximab plus radiotherapy was more
      effective than radiation therapy alone in prolonging locoregional disease
      control. In addition, more limited noncomparative data from a large trial
      indicated a 13% overall objective response rate (ORR) in platinum-refractory
      patients with SCCHN. In patients with EGFR-expressing mCRC, cetuximab plus
      irinotecan improved ORR more than cetuximab monotherapy in a trial in irinotecan
      refractory patients; however, there was no difference in overall survival (OS)
      between cetuximab plus irinotecan and cetuximab monotherapy in oxaliplatin
      refractory recipients in another trial. In an ongoing trial, progression-free
      survival (PFS) exceeded 50% after 12 weeks in irinotecan-refractory patients
      receiving three different dosages of cetuximab plus irinotecan. In another large
      trial, cetuximab monotherapy prolonged OS compared with best supportive care
      (BSC) in heavily pretreated patients. Overall, cetuximab treatment had an
      acceptable tolerability profile, with the majority of adverse events being mild
      or moderate in severity and clinically manageable. In particular, cetuximab
      therapy did not exacerbate toxicities commonly associated with chemo- or
      radiotherapeutic regimens. Albeit occurring with high incidence, adverse
      cutaneous reactions appear to be a marker for response. Results of ongoing head
      to-head comparative trials comparing cetuximab with other biological agents will
      help to establish definitively the role of cetuximab in the management of SCCHN
      and mCRC. In the meantime, cetuximab, with its highly targeted mechanism of
      action and synergistic activity with current treatment modalities, is a valuable
      treatment option in patients with SCCHN and mCRC.

PMID- 18034593
TI  - Etanercept: a review of its use in the management of ankylosing spondylitis and
      psoriatic arthritis.
AB  - Etanercept (Enbrel), a recombinant, dimeric, soluble tumour necrosis factor (TNF)
      receptor protein, is approved in various countries for the treatment of adult
      patients with ankylosing spondylitis or psoriatic arthritis. Monotherapy with
      subcutaneous etanercept 25mg twice weekly or 50mg once weekly was effective and
      generally well tolerated in patients with ankylosing spondylitis or psoriatic
      arthritis participating in several large, well designed clinical studies.
      Treatment with etanercept was more effective than placebo in reducing disease
      activity and improving health-related quality of life (HR-QOL) in both patient
      populations, and in delaying structural disease progression in patients with
      psoriatic arthritis. The beneficial response to etanercept achieved with shorter
      term treatment was sustained in studies of up to 4 years' total duration.
      Randomised, well designed, head-to-head comparisons, including pharmacoeconomic
      analyses, with other anti-TNF biological modulators are required to accurately
      position etanercept and fully establish its cost effectiveness. In the meantime,
      etanercept is a valuable treatment option for patients with ankylosing
      spondylitis or psoriatic arthritis who are suitable candidates for therapy.

PMID- 18034594
TI  - Delayed-release Multi Matrix System (MMX) mesalazine: in ulcerative colitis.
AB  - * Mesalazine appears to act locally on the mucosa of the colon and reduces the
      inflammation associated with ulcerative colitis. * Following oral administration,
      the majority (*78%) of a dose of delayed-release Multi Matrix System (MMX)
      mesalazine passes unabsorbed through the upper gastrointestinal tract to reach
      and traverse the entire length of the colon. * In a well designed phase III trial
      in patients with active, mild to moderate ulcerative colitis (n = 262),
      significantly (p < 0.01) more MMX mesalazine 2.4 (34%) or 4.8 g/day (29%)
      recipients than placebo recipients (13%) achieved clinical and endoscopic
      remission after 8 weeks of treatment.* In a second phase III trial (n = 341),
      clinical and endoscopic remission rates with MMX mesalazine 2.4 (40.5%) and 4.8
      g/day (41.2%) were significantly (p < 0.01) greater than with placebo (22.1%)
      after 8 weeks, while the remission rate with non-MMX delayed-release mesalazine
      (Asacol) [32.6%] did not differ from placebo.* Overall, MMX mesalazine was
      generally well tolerated in controlled clinical trials, with a similar incidence
      of treatment-emergent adverse events in placebo (66%) and MMX mesalazine (56%)
      recipients in a pooled analysis; most adverse events were of mild or moderate
      severity. Two of 434 MMX mesalazine recipients experienced serious adverse events
      that were considered treatment related (pancreatitis caused by mesalazine
      sensitivity).

PMID- 18034595
TI  - Delayed-release Multi Matrix System (MMX) mesalazine in ulcerative colitis: a
      viewpoint by Cosimo Prantera.

PMID- 18034596
TI  - Delayed-release Multi Matrix System (MMX) mesalazine in ulcerative colitis: a
      viewpoint by Ake Nilsson.

PMID- 18034598
TI  - Imatinib in relapsed or refractory Philadelphia chromosome-positive acute
      lymphoblastic leukaemia: a viewpoint by Barbara Wassmann.

PMID- 18034599
TI  - Imatinib in relapsed or refractory Philadelphia chromosome-positive acute
      lymphoblastic leukaemia: a viewpoint by Ronan Swords.

PMID- 18034597
TI  - Imatinib: in relapsed or refractory Philadelphia chromosome-positive acute
      lymphoblastic leukaemia.
AB  - * Imatinib inhibits the breakpoint cluster region-Abelson (BCR-ABL) tyrosine
      kinase, which is produced by the chromosomal abnormality known as the
      Philadelphia (Ph) chromosome in patients with Ph chromosome-positive acute
      lymphoblastic leukaemia (Ph+ ALL). * The clinical efficacy and safety of oral
      imatinib in patients with relapsed or refractory Ph+ ALL has been demonstrated in
      a noncomparative, open-label phase II trial (n = 48) and an expanded-access study
      (n = 353). The majority of patients received imatinib 600mg once daily. * In the
      phase II trial, imatinib induced complete haematological responses in 19% of
      patients, marrow complete responses in 10% of patients and partial marrow
      responses in 31% of patients. These were sustained for at least 4 weeks in 27% of
      patients. * The estimated median times to progression were 2-3.1 months in the
      phase II trial, the expanded-access study and a population of 68 patients pooled
      from these studies, with estimated median overall survival rates of 4.9-9 months.
      * In 22 patients receiving imatinib prior to undergoing allogeneic stem cell
      tranplantation (SCT) in the phase II trial and expanded-access study, estimated
      disease-free survival and overall survival rates 12 months after SCT were 25.5%
      and 44.8%. * Although adverse events were frequent among relapsed or refractory
      Ph+ ALL patients treated with imatinib, the majority of non-haematological
      adverse events were mild or moderate in severity.

PMID- 18034600
TI  - Imatinib in relapsed or refractory Philadelphia chromosome-positive acute
      lymphoblastic leukaemia: a viewpoint by Joseph Brandwein.

PMID- 18034602
TI  - Comparison of continuous blood glucose measurement with conventional
      documentation of hypoglycemia in patients with Type 2 diabetes on multiple daily
      insulin injection therapy.
AB  - BACKGROUND: The primary objective of this study was to investigate the difference
      in the proportion of patients with conventionally detected hypoglycemia compared
      with continuous glucose monitoring system (CGMS, Medtronic MiniMed, Sylmar, CA)
      detected glucose values < or = 60 mg/dL (< or = 3.3 mmol/L), during the 72-h CGMS
      measurement period after 8 weeks' treatment with insulin glargine. METHODS: This
      was a multicenter (n = 125), open-label, single-arm study in patients with Type 2
      diabetes mellitus (T2DM) on multiple daily injections. Patients received NPH
      insulin (2-week run-in) followed by glargine (8-week treatment phase). Glucose
      levels were measured by CGMS and self-monitored blood glucose (SMBG) profiles
      over the 72-h pre- and post-treatment phase. RESULTS: The full analysis set
      contained 367 patients [male 59%; mean age 59.2 years; mean body mass index 31.7
      kg/m(2); mean hemoglobin A1c (HbA1c) 6.9%]. At end point, 209 patients (56.9%)
      experienced hypoglycemia according to CGMS; 97 (26.4%) recorded hypoglycemia by
      conventional methods. CGMS- and SMBG-determined mean daytime glucose levels were
      similar at baseline and end point; however, nocturnal glucose levels were
      significantly lower with CGMS versus SMBG at baseline [130.2 vs. 145.0 mg/dL (7.2
      vs. 8.1 mmol/L)] and at end point [123.3 vs. 137.3 mg/dL (6.8 vs. 7.6 mmol/L)].
      Glucose levels measured by CGMS and SMBG decreased, and HbA1c levels decreased
      from 6.90% at screening to 6.67% at end point (P < 0.001). CONCLUSIONS: This
      study demonstrates that CGMS can be successfully employed in large clinical trial
      settings in patients with T2DM. This easy-to-implement method may provide
      additional insights into glucose levels and valuable information regarding the
      time patients spend within the preferred glucose range.

PMID- 18034603
TI  - Inpatient point-of-care bedside glucose testing: preliminary data on use of
      connectivity informatics to measure hospital glycemic control.
AB  - BACKGROUND: Point-of-care (POC) bedside glucose (BG) testing and timely
      evaluation of its effectiveness are important components of hospital inpatient
      glycemic control programs. We describe a new technology to evaluate inpatient POC
      BG testing and report preliminary results of inpatient glycemic control from 10
      U.S. hospitals. METHODS: We used the Remote Automated Laboratory System RALS
      Tight Glycemic Control Module (TGCM) (Medical Automation Systems,
      Charlottesville, VA) connected to the RALS-Plus to extract and analyze inpatient
      POC-BG tests from 10 U.S. hospitals for a 3-month period. POC-BG measurements
      were evaluated in aggregate from all 10 facilities for intensive care unit (ICU),
      non-ICU, and ICU + non-ICU combined. RESULTS: A total of 742,154 POC-BGs were
      analyzed. The combined (ICU + non-ICU) mean POC-BG was 159 mg/dL, compared with
      146 mg/dL for the ICU and 164 mg/dL for non-ICU. The proportion of hypoglycemic
      values (<70 mg/dL) was low at 4%, but the percentage of measurements that would
      be considered hyperglycemic (>180 mg/dL) was high, with more than 30% of values
      in the non-ICU and 20% in the ICU being elevated. CONCLUSIONS: POC-BG data can be
      captured through automated data management software and can support hospital
      efforts to evaluate and monitor the status of inpatient glycemic control. These
      preliminary data suggest that there is a need to conduct broad-based efforts to
      improve inpatient glucose management. Increasing hospital participation in data
      collection has the potential to create a national benchmarking process for the
      development of best practices and improved inpatient hyperglycemia management.

PMID- 18034604
TI  - Modeling the effect of blood glucose and physical exercise on plasma adrenaline
      in people with type 1 diabetes.
AB  - BACKGROUND: Adrenaline is often studied in people with type 1 diabetes during
      hypoglycemic episodes. Adrenaline is difficult and costly to measure, and
      therefore a pharmacokinetic model of adrenaline can be a supportive tool that
      adds information and saves measurements resources. METHODS: We have developed a
      compartment model of adrenaline secretion and elimination. It is based on input
      on physical exercise, blood glucose level, and optional infused adrenaline. The
      model parameters are identified using least square regression on published data
      of adrenaline kinetics measured in a number of different clinical studies.
      RESULTS: Simulation of published adrenaline measurements shows agreement with
      data of adrenaline infusion (R(2) = 0.9), exercise (R(2) = 0.97), and
      hypoglycemic episodes (R(2) = 0.93-0.97). The identified function describing
      adrenaline secretion during hypoglycemia shows an exponential increase for a
      blood glucose decreasing below 3.5 mmol/L and an approaching maximum around 1
      mmol/L. Exercise intensity increasing above 50% of maximal oxygen uptake maximum
      causes approximately exponential increase in adrenaline secretion. CONCLUSION:
      The model is a simple tool that can be used to simulate and predict adrenaline
      concentrations in situations of hypoglycemia, physical exercise, and adrenaline
      infusion. In conclusion, the developed model, although simple, seems to be useful
      for simulating adrenaline dynamics in situations with hypoglycemic episodes,
      physical exercise, or infusion.

PMID- 18034605
TI  - Restoring euglycemia in the basal state using continuous glucose monitoring in
      subjects with type 1 diabetes mellitus.
AB  - BACKGROUND: Our objective was to use continuous glucose monitoring to derive the
      optimal basal insulin infusion rates in adults with type 1 diabetes and using
      continuous subcutaneous insulin infusion (CSII) pumps. METHODS: In an effort to
      mimic euglycemia during the basal state, we used a standard protocol to adjust
      basal insulin infusion rates in 16 subjects with type 1 diabetes mellitus who
      were using CSII pumps. All subjects wore Continuous Glucose Monitoring System
      sensors (CGMS), Medtronic Minimed, Northridge, CA) in order to obtain around-the
      clock tracings of their glucose measurements. Subjects were asked to skip meals
      periodically in order to optimize basal insulin infusion rates, defined as the
      basal infusion rates that maintained glucose levels in the range of 65-120 mg/dL
      during the fasting state or between meals. RESULTS: In order to demonstrate
      improved glycemic control, with blunting of glucose excursion, we compared the
      baseline CGMS area under the curve (AUC) to the AUC obtained after optimizing the
      basal insulin dosages. We analyzed the curves by determining the AUC for glucose
      excursions above 110 mg/dL. The AUC for glucose excursions above 110 mg/dL was
      significantly smaller after optimization (19 +/- 13 mg/dL.day) compared to the
      baseline AUC (50 +/- 31 mg/dL.day) (P < 0.001). CONCLUSIONS: Using both a
      standard protocol for initial basal insulin infusion rates and CGMS curves to
      optimize basal infusion rates, one can improve glycemia in subjects with type 1
      diabetes using CSII.

PMID- 18034606
TI  - Comparison of in vitro stability for insulin aspart and insulin glulisine during
      simulated use in insulin pumps.
AB  - BACKGROUND: This study was designed to evaluate the stability properties of the
      marketed insulin aspart (IAsp) and insulin glulisine (IGlu) products during
      simulated continuous subcutaneous insulin infusion (CSII) for up to 10 days.
      METHODS: Plastic reservoirs containing IGlu or IAsp were placed in MiniMed 508
      infusion pumps (MiniMed, Northridge, CA) connected via an infusion set to a
      collection glass vial. Pumps were shaken continuously (30 oscillations/min, 2 cm
      amplitude) at 37 +/- 2 degrees C. Samples from reservoirs as well as pumped
      samples collected at the end of the needle, at flow rates of 0.3 U/h and 0.9 U/h,
      were tested to assess physical stability against insulin fibrillation and
      chemical stability in terms of formation of high-molecular-weight proteins (HMWP)
      and content of insulin. Baseline values were established by similar tests of IAsp
      and IGlu samples stored in the marketed glass cartridges at 5 +/- 3 degrees C
      during the entire study. RESULTS: For IGlu the physical stability against insulin
      fibrillation was reduced in both the reservoir and at needle end compared to
      baseline samples. For IAsp, physical stability increased in both the reservoir
      and at needle end with the exception of the reservoir sample at 0.9 U/h, which
      still maintained 90% physical stability compared to baseline samples. Both IAsp
      and IGlu retained a high proportion of native insulin; however, at the study's
      end, IGlu contained twice the amount of biologically inactive HMWP compared to
      IAsp. The overall retention of antimicrobial agents was higher in IAsp.
      CONCLUSIONS: The physical stability against fibrillation was reduced for IGlu,
      but not for IAsp, during simulated CSII use. A higher rate of formation of
      biologically inactive HMWP was observed for IGlu.

PMID- 18034607
TI  - Outcomes of a cardiothoracic intensive care web-based online intravenous insulin
      infusion calculator study at a Medical University Hospital.
AB  - BACKGROUND: The purpose of this study was to examine whether a web-based, on-line
      intravenous insulin (IVI) infusion calculator (IVIIC) program for the delivery of
      IVI therapy in coronary artery bypass graft (CABG) patients was superior to a
      prior IVI protocol used in the cardiothoracic intensive care unit at our
      institution. METHODS: The study included 97 CABG patients studied from October
      2004 to February 2005 pre-protocol (type 2 diabetes) and October 2005 to February
      2006 post-protocol (with or without type 2 diabetes). The IVIIC was programmed to
      resemble an algorithm whereby any patient with type 2 diabetes or a blood glucose
      (BG) greater than 120 mg/dL was started on IVI with an insulin sensitivity
      factor, a multiplier of 0.03. The calculator used the following mathematical
      formula: rate of insulin infusion/hour = (current BG - 60 mg/dL) x 0.03. RESULTS:
      Pre- and post-protocol groups for patients with type 2 diabetes were similar in
      all demographics measured, including initial age, mean age, percentage female,
      and percentage African-American. Significant differences were observed between
      pre- and post-protocol groups in mean BG recorded over a 48-h period (P <
      0.0001), percentage not at target within 48 h (P < 0.0001), mean hours to first
      BG between 80 to 120 mg/dL (P < 0.0001), mean hours to target (three consecutive
      BGs 80-120 mg/dL) (P < 0.0001), and hyperglycemic index (P < 0.0001). The
      incidence of hypoglycemia (percentage BG < 70 mg/dL) was not significantly
      increased in the post-protocol groups (P = 0.2581). CONCLUSIONS: We conclude that
      the IVIIC is a safe nurse-driven protocol with excellent BG outcomes.

PMID- 18034608
TI  - The influence of local versus global heat on the healing of chronic wounds in
      patients with diabetes.
AB  - BACKGROUND: In a previous study, it was shown that placing a subject with chronic
      diabetic ulcers in a warm room prior to the use of electrical stimulation
      dramatically increased the healing rate. However, global heating is impractical
      in many therapeutic environments, and therefore in the present investigation the
      effect of global heat versus using a local heat source to warm the wound was
      investigated. METHODS: Twenty-nine male and female subjects participated in a
      series of experiments to determine the healing associated with electrical
      stimulation with the application of local heat through a heat lamp compared to
      global heating of the subject in a warm room. Treatment consisted of biphasic
      electrical stimulation at currents at 20 mA for 30 min three times per week for 4
      weeks in either a 32 degrees C room or, with the application of local heat, to
      raise skin temperature to 37 degrees C. Skin blood flow was measured by a laser
      Doppler imager. RESULTS: Blood flow increased with either local or global
      heating. During electrical stimulation, blood flow almost doubled on the outside
      and on the edge of the wound with a smaller increase in the center of the wound.
      However, the largest increase in blood flow was in the subjects exposed to global
      heating. Further, healing rates, while insignificant for subjects who did not
      receive electrical stimulation, showed 74.5 +/- 23.4% healing with global heat
      and 55.3 +/- 31.1% healing with local heat in 1 month; controls actually had a
      worsening of their wounds. CONCLUSIONS: The best healing modality was global
      heat. However, there was still a significant advantage in healing with local
      heat.

PMID- 18034609
TI  - Assessing glucose monitor performance--a standardized approach.
AB  - BACKGROUND: Glucose monitor evaluations must be carefully designed and executed
      in order to control protocol-specific bias and random patient interferences.
      Although published guidelines and recommendations exist, investigators rarely
      incorporate consensus standards or quality guidelines into glucose monitor
      evaluation studies. METHODS: We performed a literature search for "best practice"
      quality guidelines for conducting and reporting glucose monitor evaluation
      studies. These guidelines included: Standards for Reporting Diagnostic Accuracy
      (STARD); Clinical and Laboratory Standards Institute (CLSI) C30-A2 and EP9-A2;
      U.S. Food and Drug Administration (FDA); International Federation of Clinical
      Chemistry (IFCC); Netherlands Organization for Applied Scientific Research (TNO);
      U.K. Medicines and Healthcare products Regulatory Agency (MHRA); Scandinavian
      evaluation of laboratory equipment for primary health care (SKUP); National
      Standard of the People's Republic of China (China GB/T 19634); and International
      Standards Organization (ISO 15197). RESULTS: We constructed a checklist that
      outlines a standardized approach to glucose monitor evaluations, along with
      associated references applicable to international standards and consensus
      recommendations. We expect that the checklist could be used as the basis for a
      protocol that is (1) evidence-based, (2) scientifically defensible, and (3)
      sufficiently descriptive to allow for test and result reproducibility.
      CONCLUSIONS: We propose a standardized 14-step checklist that facilitates the
      incorporation of international consensus standards, quality guidelines, and
      acceptance criteria into the design and reporting of glucose monitor evaluation
      protocols.

PMID- 18034610
TI  - Clinical predictors of glycosylated hemoglobin response to thiazolidinedione
      therapy.
AB  - BACKGROUND: The aim of this investigation was to assess clinical predictors of
      the glycosylated hemoglobin (HbA1C) response after the addition of a
      thiazolidinedione (TZD) to a biguanide, a sulfonylurea, or both in subjects with
      type 2 diabetes. METHODS: Chart review (n = 68 physicians) was used to identify
      consecutive subjects started on a TZD. Qualifying subjects had been treated with
      pioglitazone (> or = 4 mg/day) or rosiglitazone (> or = 30 mg/day) for > or = 12
      weeks. Clinical characteristics and HbA1C responses were assessed for the purpose
      of creating an initial predictive response model (Study 1). A separate sample
      from a managed care database was used to independently validate the model (Study
      2). RESULTS: Data were collected from 4085 subjects (1365 in Study 1; 2720 in
      Study 2). In Study 1, baseline HbA1C was 8.2 +/- 0.1%. Forty-five percent (611 of
      1365) and 55% (754 of 1365) were prescribed pioglitazone and rosiglitazone,
      respectively. In multivariate regression, baseline HbA1C (beta = -0.693%), age
      (beta = -0.006%), and use of multiple agents at baseline (referent = single
      agent, beta = 0.189%) were significant (P < 0.05) predictors, explaining 49% of
      the variance in HbA1C response in Study 1 and 44% of the variance in HbA1C
      response in the Study 2 sample. The model showed no material evidence of bias
      across the range of baseline HbA1C values. CONCLUSIONS: These results suggest
      that readily available clinical information, particularly baseline HbA1C,
      explains a substantial proportion of the variance in the response to TZD therapy.

PMID- 18034611
TI  - 'Drug reactions, enzymes, and biochemical genetics': 50 years later.

PMID- 18034612
TI  - FOXP3 and breast cancer: implications for therapy and diagnosis.

PMID- 18034614
TI  - Pharmacogenetics and pharmacogenomics.

PMID- 18034615
TI  - Conceptual basis and methodology of the SOPHIA study.
AB  - To clarify the role of gene polymorphisms on the effect of losartan and losartan
      plus hydrochlorothiazide on blood pressure (primary end point) and on cardiac,
      vascular and metabolic phenotypes (secondary end point) after 4, 8, 12, 16 and 48
      weeks treatment, an Italian collaborative study - The Study of the
      Pharmacogenomics in Italian hypertensive patients treated with the Angiotensin
      receptor blocker losartan (SOPHIA) - on never-treated essential hypertensives (n
      = 800) was planned. After an 8 week run-in, losartan 50 mg once daily will be
      given and doubled to 100 mg at week +4 if blood pressure is more than 140/90
      mmHg. Hydroclorothiazide 25 mg once daily at week +8 and amlodipine 5 mg at week
      +16 will be added if blood pressure is more than 140/90 mmHg. Cardiac mass
      (echocardiography), carotid intima-media thickness, 24 h ambulatory blood
      pressure, homeostatic model assessment (HOMA) index, microalbuminuria, plasma
      renin activity and aldosterone, endogenous lithium clearance, brain natriuretic
      peptide and losartan metabolites will be evaluated. Genes of the renin
      angiotensin-aldosterone system, salt sensitivity, the beta-adrenergic system and
      losartan metabolism will be studied (Illumina custom arrays). A whole-genome scan
      will also be performed in half of the study cohort (1M array, Illumina 500 GX
      beadstation).

PMID- 18034616
TI  - Patients' and healthcare professionals' views on pharmacogenetic testing and its
      future delivery in the NHS.
AB  - INTRODUCTION: There is limited empirical evidence on patients' and healthcare
      professionals' views on the provision of pharmacogenetic testing services. These
      opinions may be used to shape the development of emerging pharmacogenetic
      services and inform healthcare professionals' future educational requirements.
      OBJECTIVES: To explore patients' and healthcare professionals' views about
      pharmacogenetic testing services and their future development. METHODS: Semi
      structured interviews were conducted with patients who had been prescribed
      azathioprine for autoimmune conditions and prevention of acute rejection in renal
      transplantation. Focus groups were conducted with a range of healthcare
      professionals. Interviews and focus groups were recorded and transcribed
      verbatim. Data were analyzed using the constant comparative method. RESULTS: The
      views of 42 individuals - 25 patients and 17 healthcare professionals - were
      explored in depth. Key themes emerging from the data were: patients' and
      healthcare professionals' knowledge and experience of pharmacogenetics;
      expectations about how such a testing service could be used; and characteristics
      of service delivery. Knowledge and experience of pharmacogenetics varied.
      Pharmacogenetics was perceived to be of benefit by both groups. Patients gave
      opinions about pharmacogenetic services based on their experiences of illness,
      taking medicines and using healthcare services. Healthcare professionals based
      their opinions on how existing services are provided and access to limited
      healthcare resources. Patients had strong feelings about how this service should
      be delivered and expected high standards of explanation about potential
      pharmacogenetic tests. None of the healthcare professionals questioned expected
      to have responsibility for the future delivery of pharmacogenetic testing
      services. CONCLUSION: There is no clear model of how pharmacogenetic tests will
      be delivered in clinical practice. Patients expect to receive pharmacogenetic
      services from healthcare professionals who are able to explain the test, and
      interpret the implications for prescribing, with confidence. The gap between
      patients' high expectations for information and healthcare professionals' current
      knowledge and reluctance to deliver pharmacogenetic services highlights the
      urgent need for better education and training of healthcare professionals in
      pharmacogenetics.

PMID- 18034617
TI  - Literature-based compound profiling: application to toxicogenomics.
AB  - INTRODUCTION: To reduce continuously increasing costs in drug development,
      adverse effects of drugs need to be detected as early as possible in the process.
      In recent years, compound-induced gene expression profiling methodologies have
      been developed to assess compound toxicity, including Gene Ontology term and
      pathway over-representation analyses. The objective of this study was to
      introduce an additional approach, in which literature information is used for
      compound profiling to evaluate compound toxicity and mode of toxicity. METHODS:
      Gene annotations were built by text mining in Medline abstracts for retrieval of
      co-publications between genes, pathology terms, biological processes and
      pathways. This literature information was used to generate compound-specific
      keyword fingerprints, representing over-represented keywords calculated in a set
      of regulated genes after compound administration. To see whether keyword
      fingerprints can be used for assessment of compound toxicity, we analyzed
      microarray data sets of rat liver treated with 11 hepatotoxicants. RESULTS:
      Analysis of keyword fingerprints of two genotoxic carcinogens, two nongenotoxic
      carcinogens, two peroxisome proliferators and two randomly generated gene sets,
      showed that each compound produced a specific keyword fingerprint that correlated
      with the experimentally observed histopathological events induced by the
      individual compounds. By contrast, the random sets produced a flat aspecific
      keyword profile, indicating that the fingerprints induced by the compounds
      reflect biological events rather than random noise. A more detailed analysis of
      the keyword profiles of diethylhexylphthalate, dimethylnitrosamine and
      methapyrilene (MPy) showed that the differences in the keyword fingerprints of
      these three compounds are based upon known distinct modes of action.
      Visualization of MPy-linked keywords and MPy-induced genes in a literature
      network enabled us to construct a mode of toxicity proposal for MPy, which is in
      agreement with known effects of MPy in literature. CONCLUSION: Compound keyword
      fingerprinting based on information retrieved from literature is a powerful
      approach for compound profiling, allowing evaluation of compound toxicity and
      analysis of the mode of action.

PMID- 18034618
TI  - Factors influencing warfarin dose requirements in African-Americans.
AB  - INTRODUCTION: African-Americans are under-represented in studies assessing
      contributors to warfarin response. Our primary objective was to determine whether
      the genes for cytochrome P450 (CYP) 2C9, nicotinamide adenine dinucleotide
      phosphate, reduced, quinone oxidoreductase (NQO1) and vitamin K epoxide reductase
      complex subunit 1 (VKORC1) are associated with warfarin dose requirements in
      African-Americans. PATIENTS AND METHODS: The following factors were assessed:
      demographics; clinical data; the CYP2C9 Arg144Cys (*2), Ile358Leu (*3) and
      Asp360Glu (*5); NQO1 Pro187Ser (*1/*2); and VKORC1 G6853C genotypes were analyzed
      in 115 African-Americans on stable warfarin doses. RESULTS: Allele frequencies
      were 0.05 for the CYP2C9 *2, *3 or *5 alleles; 0.20 for NQO1 *2; and 0.25 for
      VKORC1 6853C. Possession of a CYP2C9*2, *3 or *5 allele was associated with a 38%
      lower warfarin dose compared with the *1/*1 genotype (30 +/- 13 vs 48 +/- 18
      mg/week; p = 0.003). Neither the NQO1 *1/*2 nor VKORC1 G6853C genotype was
      associated with warfarin dose requirements in the population as a whole or in
      CYP2C9*1 allele homozygotes. Multiple regression analysis revealed that CYP2C9
      genotype (p = 0.015), age (p < 0.001) and body surface area (p < 0.001) were
      jointly associated with warfarin dose requirements, and together explained 33% of
      the variability in warfarin dose requirements among African-Americans.
      DISCUSSION: Our data suggest that CYP2C9 genotype, age and body size are
      important determinants of warfarin dose requirements in African-Americans. Our
      data further suggest that the VKORC1 G6853C polymorphism alone may not be useful
      for predicting warfarin dose requirements in this racial group.

PMID- 18034619
TI  - Allelic variants in the CYP2C9 and VKORC1 loci and interindividual variability in
      the anticoagulant dose effect of warfarin in Italians.
AB  - INTRODUCTION: Warfarin is currently considered to be the anticoagulant of choice
      in the long-term treatment and prevention of thromboembolic events. However, it
      presents a narrow therapeutic range and a great interindividual dose variability.
      We investigated the influence of variants of the VKORC1 and CYP2C9 loci on the
      mean weekly warfarin dose (MWWD) required to reach stabilized therapeutic
      international normalized ratio, in order to confirm and to estimate the
      contribution of common genetic variability of these two genes in an Italian
      population and to search for novel rare VKORC1 alleles. METHODS: A total of 148
      patients were followed for 6 months and analyzed for VKORC1 and CYP2C9 gene
      variants. Analysis of variance and multiple linear regression analysis were used
      to study the contribution of each genetic factor to MWWD requirement. RESULTS:
      The complete sequencing of the VKORC1 coding region did not reveal the presence
      of exonic variants, while two common noncoding SNPs were highly associated: the T
      allele of VKORC1 1173C>T SNP (tag-SNP of H1-H2 haplotypes) is highly associated
      with low MWWD (p < 0.0001), while the A allele of VKORC1 3730G>A SNP (tag-SNP of
      H9 haplotype) is associated with high MWWD (p = 0.001). Also, CYP2C9*2
      (Arg144Cys) and CYP2C9*3 (Ile359Leu) variant alleles were significantly
      associated with low MWWD (p = 0.003 and 0.027, respectively). According to a
      multiple linear regression model including, besides VKORC1 and CYP2C9 SNPs, also
      age and weight, this percentage reaches 56% (gender is not significant).
      DISCUSSION: Our results clearly indicate VKORC1 as the gene with the largest
      contribution to MWWD. Analyzing only one tag SNP of VKORC1 gene (1173C>T), it is
      possible to foresee 20% of the total variability. Our results may contribute to
      give useful indications for clinicians especially in the initiation of therapy so
      as to avoid the risk of adverse events.

PMID- 18034620
TI  - 677C>T and 1298A>C MTHFR polymorphisms affect methotrexate treatment outcome in
      rheumatoid arthritis.
AB  - INTRODUCTION: Methotrexate (MTX), widely used in the treatment of rheumatoid
      arthritis (RA), inhibits dihydrofolate reductase and folate-dependent enzymes.
      Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and
      has been shown to be polymorphic, affecting the enzyme activity. METHODS: To
      examine the association between 677C>T and 1298A>C MTHFR polymorphisms and MTX
      efficacy in the treatment of RA, a total of 174 RA patients, treated with MTX
      plus methylprednisone 4 mg and folic acid 5 mg were analyzed. RESULTS: In
      univariate regression analysis model, the MTHFR 677T allele was associated with
      significantly higher frequency of remission, whereas in the case of the 1298C
      allele, a tendency for higher remission rate was observed. In multivariate
      regression analysis, the presence of both 677T and 1298C alleles was associated
      with an increased frequency of remission. CONCLUSION: The results of our study
      suggest that the MTHFR 677T and 1298C alleles may be associated with an increased
      rate of RA remission in patients treated with MTX receiving high doses of folic
      acid supplementation.

PMID- 18034621
TI  - Methylenetetrahydrofolate reductase (MTHFR) variants and fluorouracil-based
      treatments in colorectal cancer.
AB  - 5-fluorouracil (5FU)-based treatments remain the main chemotherapy for colorectal
      cancer. Optimal cytotoxicity of fluoropyrimidines requires elevated CH(2)FH(4)
      tumoral concentrations, controlled by the methylenetetrahydrofolate reductase
      (MTHFR) enzyme, which irreversibly converts CH(2)FH(4) into 5
      methyltetrahydrofolate. The MTHFR gene is subject to several polymorphisms, of
      which the 677C>T and 1298A>C SNPs are the two most commonly linked with altered
      enzyme activity. Since a drop in MTHFR enzymatic activity may theoretically favor
      an increase in intracellular CH(2)FH(4) concentrations, it can be hypothesized
      that tumors exhibiting the rare MTHFR variants may be more sensitive to 5FU
      cytotoxicity. Accordingly, experimental data have shown that rare MTHFR variants
      in position 677 and 1298 are more sensitive to 5FU. However, results of clinical
      data do not concord regarding the influence of MTHFR genotype on tumoral
      CH(2)FH(4) concentration, 5FU responsiveness, patient survival and 5FU-related
      toxicity. These discrepancies may result from the interpatient variability
      arising from the individual folate status, as well as from the limited role of
      fluoropyrimidines in the current chemotherapy regimen administered in colorectal
      cancer.

PMID- 18034622
TI  - Measuring biomarkers to assess the therapeutic effects of PPAR agonists?
AB  - The metabolic syndrome is defined as a clustering of cardiovascular risk factors
      with insulin resistance, including dyslipidemia, coagulation disturbances and
      hypertension. Activators of the peroxisome proliferator-activated receptors
      (PPARs) modulate several of the metabolic risk factors predisposing to
      atherosclerosis. Fibrates are hypolipidemic drugs acting through activation of
      PPARalpha, whereas glitazones are insulin sensitizers activating PPARgamma. In
      addition, these drugs exert pleiotropic anti-inflammatory actions. In this
      review, we will focus on the effects of fibrates and glitazones on biomarker
      modulation and their usefulness in the treatment of cardiovascular disease.

PMID- 18034623
TI  - Pharmacogenetics of the PPAR genes and cardiovascular disease.
AB  - The goal of pharmacogenetics is to define the genetic determinants of individual
      drug responsiveness, and thereby provide personalized treatment to each
      individual. The peroxisome proliferator-activated receptors (PPARs) are
      polypeptide products of a set of related genes functioning to regulate several
      cellular processes that are central to cardiovascular health and disease. Given
      their pleiotropic roles in lipid and glucose homeostasis, cardiac energy balance
      and regulation of adipocyte release of circulating inflammatory factors, it is
      not surprising that PPARs represent an attractive target for clinical
      investigation and intervention in disease states, such as diabetes, obesity,
      atherosclerosis, cardiomyopathy, cardiac hypertrophy and heart failure. Research
      into the manipulation of PPAR function by pharmacologic agents has already
      resulted in important advances in the treatment of diabetes mellitus and
      cardiovascular disease. It follows that PPAR pharmacogenetics promises important
      advances in the personalized treatment of cardiovascular disease.

PMID- 18034624
TI  - CYP2D6 polymorphism: implications for antipsychotic drug response, schizophrenia
      and personality traits.
AB  - The CYP2D6 gene is highly polymorphic, causing absent (poor metabolizers),
      decreased, normal or increased enzyme activity (extensive and ultrarapid
      metabolizers). The genetic polymorphism of the CYP2D6 influences plasma
      concentration of a wide variety of drugs metabolized in the liver by the
      cytochrome P450 (CYP) 2D6 enzyme, including antipsychotic drugs used for
      schizophrenia treatment. Additionally, CYP2D6 is involved in the metabolism of
      endogenous substrates in the brain, and reported to be located in regions such as
      the cortex, hippocampus and cerebellum, which are impaired in schizophrenia.
      Moreover, recently we have found that CYP2D6 poor metabolizers are under
      represented in a case-control association study of schizophrenia. Furthermore,
      null CYP2D6 activity in healthy volunteers is associated with personality
      characteristics of social cognitive anxiety, which may bear some resemblance to
      milder forms of psychotic-like symptoms. In keeping with this, CYP2D6 may
      influence, not only variability to drug response, but also vulnerability to
      disease in schizophrenia patients.

PMID- 18034625
TI  - Growing surplus of frozen embryos in China offers opportunities for the
      development of human embryonic stem cell banking.

PMID- 18034628
TI  - Randomized, controlled, single-blind study on use of autologous keratinocytes on
      a transfer dressing to treat nonhealing diabetic ulcers.
AB  - AIM: To compare the rate of healing of diabetic neuropathic ulcers using cultured
      autologous keratinocytes delivered on chemically defined transfer discs (Myskin)
      (active treatment) versus healing obtained with cell-free discs (placebo).
      MATERIALS AND METHODS: After a 4-week lead-in period patients (randomly assigned)
      received active or placebo treatments weekly for 6 weeks. All patients then
      received active treatments for a maximum of 12 treatments where required.
      Altogether, 16 patients with a total of 21 ulcers resistant to conventional
      therapy were recruited from four specialist diabetic centers in three cities.
      RESULTS: All 21 ulcers were treated and of these ten healed and eight improved,
      with two failing to respond (one ulcer was lost due to autoamputation). For
      analysis according to the study criteria, however, only the 12 patients with 12
      index ulcers who completed treatment protocols were eligible - five in the
      placebo group and seven in the active group. Of these, five ulcers healed
      completely and seven were reduced by more than 50%. Complete healing took a
      median of ten active applications. CONCLUSIONS: Repeated regular applications of
      the patient's keratinocytes, delivered on the carrier dressing, initiated wound
      healing in ulcers resistant to conventional therapy, with 18 out of 21 ulcers
      responding. The healing observed did not appear attributable to patient
      recruitment or the cell-free carrier dressing but to the delivery of the cultured
      cells.

PMID- 18034629
TI  - Development and manufacture of an investigational human living dermal equivalent
      (ICX-SKN).
AB  - AIM: To design and manufacture an investigational living skin graft replacement
      (ICX-SKN) that is able to incorporate into the host, providing healing by primary
      intent without the need for a second intervention. MATERIALS & METHODS: The ICX
      SKN skin graft replacement has been designed as an allogeneic dermal substitute
      comprising an extracellular matrix composed largely of human collagen and human
      dermal fibroblast cells (HDFs). ICX-SKN is first formed by casting a provisional
      matrix of fibrin, into which HDFs are seeded. Through a process of maturation,
      HDFs are induced to lay down collagen and other extracellular matrix materials
      and, as the construct matures, the original fibrin is largely replaced by
      collagen, which provides tensile strength and flexibility to the construct. In
      order to design a product and manufacturing system that lends itself to large
      scale production the process was developed as a discontinuous process consisting
      of four stages: 1. batch casting and maturation of the initial construct (pSKN),
      2. freeze-drying of pSKN to produce a second intermediate (dSKN), 3.
      sterilization by gamma-irradiation of dSKN to produce a third intermediate
      (sSKN), and finally, 4. repopulation of sSKN by fresh HDFs to produce the final
      product, ICX-SKN skin graft replacement. Preliminary characterization of ICX-SKN
      and its application in a preclinical model are described. RESULTS: The 7-week
      maturation period resulted in a construct (pSKN) with robust handling properties,
      which was composed mainly of human collagen I. Following development of a process
      for freeze-drying and subsequent sterilization, the matrix was successfully
      repopulated with fresh HDFs. In addition, it was demonstrated that human
      keratinocytes attached and differentiated on the matrix. Application of human
      keratinocytes to the repopulated constructs (ICX-SKN) resulted in expression of
      markers of basement membranes that was largely dependent on the presence of
      living HDFs on the constructs. ICX-SKN graft replacements applied to excision
      wounds in mice healed and were rapidly re-epithelialized. CONCLUSIONS: ICX-SKN
      has been developed as a platform product that can be used as a skin graft
      replacement and the process by which it is manufactured has been designed for the
      product to be available to the end-user off-the-shelf and for ease-of-use in
      practice.

PMID- 18034630
TI  - A xenobiotic-free culture system for human limbal epithelial stem cells.
AB  - AIMS: Murine 3T3 feeder cells are commonly used for stem cell expansion. Although
      'feeder-free' systems are being developed for a variety of stem cells including
      embryonic, the use of feeder cells currently remains optimal for the expansion of
      epithelial stem cells. In this study, MRC-5, a human embryonic fibroblast cell
      line, has been investigated for its potential use as a feeder layer in human
      limbal epithelial (HLE) cell expansion under serum-free conditions, with the aim
      of developing a xenobiotic-free culture system for therapeutic corneal
      regeneration applications. MATERIALS AND METHODS: MRC-5 feeder cells were
      compared with J2 3T3 mouse fibroblasts, in both serum-supplemented and serum-free
      conditions, in terms of their relative ability to support HLE cell metabolic
      activity, expression of the putative stem cell markers ABCG2 and P63 alpha, cell
      differentiation using the cornea-specific cytokeratin 3 antibody and colony
      forming efficiency. RESULTS: The proportion of HLE stem cells maintained was
      determined by functional colony-forming efficiency assays. The metabolic activity
      results showed that HLE cells cultured on MRC-5 fibroblasts under serum-free
      conditions proliferated as well as cells cultured on J2 cells under serum-free
      conditions. Moreover, the HLE cultured on MRC-5 fibroblasts under serum-free
      conditions expressed high levels of putative stem cell markers ABCG2 and P63
      alpha and low levels of the differentiation marker CK3, indicating that they
      retained poorly differentiated 'stem cell-like' characteristics under those
      culture conditions. Clonal analysis of HLE cells cultured on growth-arrested
      feeder layers of J2 and MRC-5 fibroblasts showed that cells expanded on MRC-5 and
      J2 fibroblasts in serum-free conditions had a colony-forming efficiency of
      approximately 1.5%, indicating the maintenance of stem cells. CONCLUSIONS: These
      results demonstrate feasibility of expanding HLE cells for clinical purposes by
      using a human fibroblast cell line as a feeder layer, avoiding the use of bovine
      serum, while preserving the proliferative potential and stem cell characteristics
      of HLE cells.

PMID- 18034631
TI  - Transplanted neural progenitor cells survive and differentiate but achieve
      limited functional recovery in the lesioned adult rat spinal cord.
AB  - Endogenous repair after injury in the adult CNS is limited by a number of factors
      including cellular loss, inflammation, cavitation and glial scarring. Spinal cord
      neural progenitor cells (SCNPCs) may provide a valuable cellular source for
      promoting repair following spinal cord injury. SCNPCs are multipotent, can be
      expanded in vitro, have the capacity to differentiate into CNS cell lineages and
      are capable of long-term survival following transplantation. AIMS & METHOD: To
      determine the extent to which SCNPCs may contribute to spinal cord repair SCNPCs
      isolated from rat fetal spinal cord were expanded ex vivo and transplanted into
      the adult rat spinal cord after a dorsal column crush lesion. RESULTS: The
      survival and distribution of transplanted cells were examined at 24 h, 1, 2 and 6
      weeks after injury. Transplanted cells were identified at all time points,
      located mainly at the lesion perimeter, indicating good post-transplant cell
      survival. Furthermore, SCNPCs maintained their ability to differentiate in vivo,
      with approximately 40% differentiating into cells with a glial morphology, whilst
      8% displayed a neural morphology. Transplanted animals were also assessed on a
      number of behavioral tasks measuring sensorimotor and proprioceptive function to
      determine the extent to which SCNPC transplants might attenuate lesion-induced
      functional deficits. SCNPCs failed to promote significant functional recovery,
      with a small improvement observed in only one of the four tasks employed,
      primarily related to improvements in sensory function. Tracing of the
      corticospinal tract and ascending dorsal column pathway revealed no regeneration
      of the axons beyond the lesion site. CONCLUSIONS: These data indicate that,
      although transplanted SCNPCs show good survival in the spinal cord injury
      environment, combination with other treatment strategies is likely to be required
      for these cells to fully exert their therapeutic potential.

PMID- 18034632
TI  - Toxicity testing using hematopoietic stem cell assays.
AB  - For over 40 years, in vitro assays have been used to understand the complex
      system of hematopoiesis. Now, several of these assays are undergoing resurgence
      as scientists in academia and industry are discovering how these assays can be
      utilized in drug discovery and development. These assays use primary cells from
      various hematopoietic tissues in multiple species to provide high content
      information. While conditions in the human body cannot be completely reproduced
      in vitro, hematopoietic colony-forming cell assays are proving to be a clinically
      relevant tool to evaluate potential toxic effects of new compounds. The ability
      to use these assays as a replacement of, or in conjunction with, high-throughput
      screening assays and high priced in vivo assays can improve the success of the
      decision-making process, saving time and costs during drug development.

PMID- 18034633
TI  - Road for understanding cancer stem cells: model cell lines.
AB  - There is increasing evidence suggesting that stem cells are susceptive to
      carcinogenesis and, consequently, can be the origin of many cancers. Recently,
      the neoplastic potential of stem cells has been supported by many groups showing
      the existence of subpopulations with stem cell characteristics in tumor biopsies
      such as brain and breast. Evidence supporting the cancer stem cell hypothesis has
      gained impact due to progress in stem cell biology and development of new models
      to validate the self-renewal potential of stem cells. Recent evidence on the
      possible identification of cancer stem cells may offer an opportunity to use
      these cells as future therapeutic targets. Therefore, model systems in this field
      have become very important and useful. This review will focus on the state of
      knowledge on cancer stem cell research, including cell line models for cancer
      stem cells. The latter will, as models, help us both in the identification and
      characterization of cancer stem cells and in the further development of
      therapeutic strategies including tissue engineering.

PMID- 18034634
TI  - What can be learnt from the Japanese regulatory approach to tissue engineered
      products?
AB  - The Japanese government has recognized the challenges its rapidly aging
      population presents, especially in terms of healthcare provision, and is focusing
      on the potential of regenerative medicine to address them. The country has
      consequently embarked upon a national program to support development of this
      field. In 1999 Japan initiated a national research project in science and
      technology, known as the Millennium Project, whose areas of research include
      tissue engineering covering skin, cornea, bone, cartilage, blood vessels, nerves
      and bone marrow. In this context, at a time when regulations for tissue
      engineered products are being developed and revised in the USA and at the
      European level, it is interesting to investigate what type of framework Japanese
      regulators have designed to deal with these products in order to see what lessons
      might be learnt by UK, US and EU regulators. This paper reviews negative and
      positive aspects of the current regulatory situation that applies to tissue
      engineered products in Japan but will mostly focus on examples of good practice,
      such as the pragmatism that underpins the Japanese regulatory strategy, the
      international involvement of the country when it comes to developing regulatory
      standards and the promotion of a supportive public environment.

PMID- 18034635
TI  - Novocell, Inc.
AB  - Novocell, Inc. is a stem cell engineering company creating, delivering and
      commercializing cell and drug therapies for diabetes and other chronic diseases.
      The use of human embryonic stem cells provides a scalable source of any
      differentiated lineage that has potential for cell replacement therapy, as well
      as tools for drug discovery to create regenerative medicines.

PMID- 18034637
TI  - Relationship between methionine synthase, methionine synthase reductase genetic
      polymorphisms and deep vein thrombosis among South Indians.
AB  - BACKGROUND: The rationale behind this study was to examine the relationship
      between polymorphisms in genes that regulate remethylation of homocysteine to
      methionine, i.e., methionine synthase (MTR A2756G) and methionine synthase
      reductase (MTRR A66G), and risk of deep vein thrombosis (DVT) in a South Indian
      cohort (163 DVT cases and 163 controls), as elevated homocysteine has been
      documented as an independent risk factor for DVT in the same cohort. METHODS:
      Plasma homocysteine analysis was carried out by reverse phase HPLC. The MTR
      A2756G and MTRR A66G genetic polymorphisms were detected using PCR-restriction
      fragment length polymorphism method. For statistical analyses, Fisher's exact
      test was used for categorical variables and Student's t-test and analysis of
      variance were used for continuous variables. RESULTS: The MTRR 66GG genotype was
      associated with a 2.74-fold [95% confidence interval (CI): 1.73, 4.34] risk of
      DVT. The MTR A2756G polymorphism was not a risk factor. MTRR GG/MTR AG and MTRR
      GG/MTR GG genotypes cumulatively were found to increase the risk of DVT by 2.38
      fold (95% CI: 1.43, 3.96). A positive association was observed between plasma
      homocysteine and the MTRR G allele, and the MTR G allele was shown to have an
      additive effect. The risk associated with the MTRR 66GG genotype was further
      increased in subjects compound heterozygous for methylene tetrahydrofolate
      reductase (MTHFR) [odds ratio (OR): 3.46, 95% CI: 1.38, 8.63]. CONCLUSIONS: The
      MTRR 66GG genotype is a risk factor for DVT among South Indians. This risk is
      increased further in the presence of the MTHFR 677CT/1298AC genotype.

PMID- 18034638
TI  - Analytical evaluation of the Optium Xido blood glucose meter.
AB  - BACKGROUND: The main prevention of chronic diabetic complications is maintaining
      near normoglycemia. In this study, evaluation of analytical performance of the
      Optium Xido blood glucose meter designed for patients' self-monitoring of
      glycemia was carried out. METHODS: Glucose concentrations were measured in 118
      EDTA blood samples using the Xido glucose meter and the GOD/PAP method on a
      Modular P clinical analyzer. The results obtained were used for the assessment of
      accuracy, precision and linearity. Performance of the Xido glucose meter was also
      assessed using four different reagent strip lots, and the between-lot variation
      was calculated. RESULTS: The within-run imprecision coefficient of variation (CV)
      amounted to 4.2%. Good response linearity was found in glucose concentrations of
      31-444 mg/dL (1.7-24.7 mmol/L). In the concentration range studied, the glucose
      meter error was 5.14% and the linear regression equation was y=0.91x+6.2,
      (r=0.984). The Passing-Bablok agreement test indicated good concordance of
      results. However, for glucose concentrations<100 mg/dL (5.6 mmol/L) (n=69) the
      error was 6.82% with regression equation y=0.86x+5.9 (r=0.757). Between-lot
      differences amounted to 0.7%-18.2%. CONCLUSIONS: The Xido glucose meter has good
      precision and accuracy when compared to the laboratory method and meets the
      quality recommendations of the National Committee of Clinical Laboratory
      Standards (NCCLS, currently the Clinical Laboratory Standards Institute), the
      National Academy of Clinical Biochemistry (NACB) and the International
      Organization for Standardization (ISO). However, between-lot variability may
      result in differences between day-to-day results when the device is continuously
      used. Therefore, the validation of new lots of reagent strips with a laboratory
      method is recommended.

PMID- 18034639
TI  - Simultaneous genotyping of the three lactose tolerance-linked polymorphisms LCT 
      13907C>G, LCT -13910C>T and LCT -13915T>G with Pyrosequencing technology.
AB  - BACKGROUND: We required a new genotyping method for the diagnosis of adult
      hypolactasia, which would allow the simultaneous genotyping of three known
      polymorphic loci linked to lactose tolerance (LCT -13907C>G, LCT -13910C>T and
      LCT -13915T>G) in a single PCR/pyrosequencing test run. METHOD: We utilized
      Pyrosequencing technology, a DNA-sequence-by-synthesis technique. RESULTS: The
      developed Pyrosequencing method allowed genotyping of the three loci LCT 
      13907C>G, LCT -13910C>T and LCT -13915T>G in a single PCR/pyrosequencing test
      run. A separate Pyrosequencing assay was developed for genotyping of the LCT 
      14010G>C mutation. The methods were evaluated in 116 clinical samples from
      patients of non-European descent, sent to the laboratory for diagnosis of adult
      hypolactasia. The "African" mutations LCT -13907C>G and LCT -13915T>G were found
      in subjects originating not only from Somalia, Ethiopia and Eritrea but also in
      Arabs and Iranians. Several compound heterozygotes LCT -13907CG/-13915TG were
      found among Ethiopian, Eritrean and Somalian subjects. No subject with the LCT 
      14010G>C mutation was found among the studied subjects. Advantages compared to
      the other genotyping methods are less staff hands-on time than, e.g., restriction
      fragment length polymorphism (RFLP) analyses, avoiding radioactivity as in the
      originally described isotope-minisequencing and in addition, Pyrosequencing is a
      direct DNA sequencing technique which gives unambiguous genotyping results as
      well as some redundant sequence information beyond the single nucleotide
      polymorphism (SNP) position, which serves as a valuable internal control obtained
      for each sample. CONCLUSIONS: Pyrosequencing is a robust genotyping modality
      suitable for clinical genotyping of patients not only of European, but also of
      African or Middle Eastern descent, who may harbor any combination of the three
      LCT mutations, LCT -13907C>G, LCT -13910C>T, LCT -13915T>G.

PMID- 18034640
TI  - Isoenzymes of N-acetyl-beta-hexosaminidase in human pleomorphic adenoma and
      healthy salivary glands: a preliminary study.
AB  - BACKGROUND: Pleomorphic adenoma (PA) is a benign tumour of the salivary gland
      with a tendency to malignancy which creates many diagnostic problems. N-acetyl
      beta-hexosaminidase (HEX) is a lysosomal exoglycosidase involved in degradation
      of oligosaccharide chains of glycoproteins, glycolipids and glycosaminoglycans,
      known as a potential tumour marker. In the majority of tissues and body fluids,
      HEX exists as two major isoenzymes: HEX A and HEX B. The aim of our study was to
      evaluate HEX A and HEX B activity in healthy and PA human salivary glands using
      colorimetric and isoelectrofocusing methods. METHODS: PA (n=8) and
      macroscopically unchanged salivary glands (n=8), served as controls, were used
      for the study. After preliminary preparation, isoenzymes of HEX were determined
      by colorimetric and isoelectrofocusing methods. RESULTS: Total activity of HEX,
      as well as HEX A and HEX B, in PA specimens determined by a colorimetric method
      was significantly higher compared with normal human salivary gland specimens.
      After isoelectrofocusing, in normal human salivary and PA glands, two sets of HEX
      isoforms were found corresponding to HEX A and HEX B. There was no significant
      difference in the amount of HEX A and HEX B isoforms. In PA tissue, activities of
      HEX isoforms in the pI ranges 1, 3b, 6 and 8 were significantly lower, and in
      ranges 5 and 8 significantly higher than in normal tissue. The observed
      significant shifts were localised mostly in HEX B activity area. CONCLUSIONS: The
      present data indicate that HEX activity and activity of its isoenzymes in tumour
      specimens is significantly and consistently elevated, and thus suggest the need
      for further studies on the degradation of glycoconjugates, both in healthy
      salivary glands and PA. It appears that HEX may be considered as a new tumour
      marker in these salivary gland diseases.

PMID- 18034641
TI  - Lipid peroxidation in stroke patients.
AB  - BACKGROUND: Paraoxonase is high-density lipoprotein (HDL)-associated
      esterase/lactonase implicated to play a role in the antioxidant and anti
      inflammatory properties exerted by HDL. Increasing evidence support a role of
      free radicals and oxidative stress in neuronal damage induced by ischemia
      reperfusion. The aim of this study was to further investigate the relationship
      between lipoprotein oxidative damage and stroke. METHODS: We compared the
      paraoxonase activity and levels of lipid hydroperoxides in plasma isolated from
      healthy subjects (n=50) and from stroke patients (n=49). Moreover, the
      correlations between biochemical markers and the National Institute of Health
      Stroke Scale (NIHSS), which is widely used to study neurological severity, were
      evaluated. RESULTS: Our results demonstrated, for the first time, that the
      activity of paraoxonase in plasma of stroke subjects was significantly lower than
      controls (p<0.001) and the levels of lipid hydroperoxides were significantly
      higher in plasma from patients (p<0.001). Moreover, using linear regression
      analysis, significant correlations between the activity of paraoxonase, lipid
      peroxidation and the severity of neurological deficit at admission were observed.
      CONCLUSIONS: These results provide further evidence that oxidative stress and
      impairment of the antioxidant system may play a role in stroke. Antioxidant
      activity of plasma may be an important factor providing protection from
      neurological damage caused by stroke-associated oxidative stress.

PMID- 18034642
TI  - Analysis of serum and urinary lysophospholipase D/autotaxin in nephrotic
      syndrome.

PMID- 18034643
TI  - Recent findings into the potential of gene therapy to reverse heart failure.
AB  - The incidence of heart failure (HF) is ever growing and the mortality of HF
      patients is similar to patients suffering from cancer disease. The central
      clinical problem is a lack of therapies to target the underlying molecular
      defects that lead to chronic ventricular dysfunction. Substantial evidence points
      to a final common pathway in failing myocardium, including distinct changes in
      intracellular Ca2+-cycling and beta-adrenergic receptor signaling. An attractive
      strategy to address these alterations is cardiac gene therapy and several
      distinct approaches have been undertaken during the last decade with impressing
      therapeutic benefit, at least in animal HF models. The present focus of research
      is the clinical translation of cardiac gene therapy including the optimization of
      vectors, delivery strategies and testing the compatibility with established
      pharmacologic treatment to improve the prognosis of HF in the near future.

PMID- 18034644
TI  - Prospects for and barriers to a fungal vaccine.
AB  - Vaccination is a desirable strategy to prevent life-threatening fungal
      infections. Candidiasis is the most common invasive fungal infection, and
      promising vaccine targets are nearing clinical testing to prevent such
      infections. One barrier to developing antifungal vaccines is the perceived risk
      of blunted immune responses in at-risk patients. However, vaccines stimulate
      effective immune responses even in highly immunocompromised patients. The biggest
      barrier to development of fungal vaccines is the lack of available capital to
      translate discoveries made at the bench into biologics used at the bedside.
      Nevertheless, vaccines targeting invasive fungal infections are an extremely
      promising avenue of research and development. It is desirable that additional
      sources of capital be made available to academic scientists to facilitate
      development of such vaccines.

PMID- 18034645
TI  - Hematopoietic stem cell transplantation for chronic lymphocytic leukemia:
      potential cure for an incurable disease.
AB  - Hematopoietic stem cell transplantation (HSCT) has been used as a treatment
      modality in patients with chronic lymphocytic leukemia (CLL). Allogeneic HSCT is
      the only therapy at present that has curative potential in patients with CLL.
      Allogeneic HSCT using standard myeloablative regimens has been generally
      associated with high treatment mortality rates and autologous HSCT with high
      relapse rates. Over the last decade the use of reduced intensity conditioning
      (non-myeloablative) regimens have reduced the treatment-related mortality after
      allogeneic-HSCT without affecting the graft-versus-leukemia effectiveness. In
      addition, the development of molecular and biologic markers has identified high
      risk CLL patients that may benefit from earlier treatment with HSCT. This review
      summarizes the use of existing prognostic markers in CLL and their use in HSCT,
      and the advances, indications and clinical outcomes of both autologous HSCT and
      allogeneic HSCT.

PMID- 18034646
TI  - Gene therapy for chronic granulomatous disease.
AB  - Patients with chronic granulomatous disease (CGD) cannot generate reactive oxygen
      metabolites, and suffer from severe recurrent infections and dysregulated
      inflammation. Haematopoietic stem cell transplantation is the only established
      option for definitive cure for patients with a suitable donor and is indicated
      when conventional prophylaxis and therapy with antimicrobial medication fail.
      Gene therapy has the potential to cure CGD, and several clinical trials have been
      conducted since 1997. Whereas initial studies resulted in low and short-term
      engraftment of CGD-corrected cells, recent trials demonstrated clinical benefit
      when engraftment was enhanced by busulfan conditioning prior to infusion of gene
      corrected cells. However, the progress in gene therapy has been hampered by the
      appearance of insertional mutagenesis causing leukaemia in a trial for patients
      with X-linked severe combined immunodeficiency and by the emergence of dominant
      clones in a recent trial for the X-linked form of CGD. These findings stimulated
      the development of modified vector systems that demonstrate reduced genotoxicity
      in vitro and in animal models. New gene therapy protocols that allow efficient
      gene transfer and durable expression but limit the risk for insertional
      mutagenesis are envisioned to become an important therapeutic option for patients
      with CGD.

PMID- 18034647
TI  - Polycation-based nanoparticle delivery for improved RNA interference
      therapeutics.
AB  - Small-interfering RNA (siRNA)-mediated silencing of genes implicated in disease
      by the process of RNA interference offers a novel genetic medicine approach.
      Polymeric nanoparticles (or polyplexes) formed by self-assembly of polycations
      with siRNA can be used for site-specific delivery, cellular uptake and
      intracellular trafficking as a strategy to improve the therapeutic potential of
      siRNA. This review describes the application of polyplexes for in vivo delivery
      of synthetic siRNA with focus given to systemic and mucosal routes and in vivo
      requirements. Issues including use of stimuli-responsive systems for
      intracellular trafficking of siRNA are discussed as part of necessary future
      directives towards the development of RNA-based clinical therapeutics.

PMID- 18034648
TI  - MicroRNAs in synapse development: tiny molecules to remember.
AB  - MicroRNAs are a recently discovered class of small non-coding RNAs that play a
      key role in post-transcriptional gene regulation during development and disease.
      MicroRNAs are abundant in the nervous system and have already been shown to have
      an important function during neuronal patterning and cell specification. It is
      now becoming increasingly evident that they are also essential for synaptic
      development and that they might contribute to the etiology of neuronal diseases
      characterized by synaptic dysfunction. This review focuses on the recent examples
      that describe a function of microRNAs in synapse formation and plasticity, and
      discusses how the microRNA pathway might be exploited to treat neurologic
      diseases.

PMID- 18034649
TI  - Roles of microRNAs and their targets in cancer.
AB  - MicroRNAs (miRNAs) are a new class of regulator of gene expression. Initially
      discovered as regulators of developmental timing in invertebrates, miRNAs have
      subsequently been implicated in a variety of biologic processes. In recent years,
      their importance for human disease has become apparent. In particular, there is
      increasing evidence of their role in cancer, both as oncogenes and tumor
      suppressors, making them appealing targets for therapy. Furthermore, the
      variations in the abundance of miRNAs in different tissues and cancers offer a
      specific 'signature' that can be useful in diagnosis.

PMID- 18034650
TI  - The immunological challenges of malaria vaccine development.
AB  - Malaria remains an important public health problem throughout the tropical world
      causing immense human suffering and impeding economic development. Despite
      extensive research for > 100 years, options for preventing malaria remain limited
      to vector control and chemoprophylaxis. The complexity of the organism and its
      life cycle have, thus far, thwarted vaccine development and exacerbated the
      perennial problems of drug resistance. Nevertheless, development of a vaccine
      against malaria that reduces morbidity and mortality, and ideally also reduces
      transmission, has long been seen as an essential component of a sustainable
      malaria control strategy. In this article the authors review the biological
      challenges of malaria vaccine development, summarise some of the recent advances
      and offer some immunological insights which might facilitate further research.

PMID- 18034651
TI  - Novel strategies for Alzheimer's disease treatment.
AB  - Considerable progress has been made in recent years towards better understanding
      the pathogenesis of Alzheimer's disease (AD), a dementing neurodegenerative
      disorder that affects > 10 million individuals in the US and Europe combined.
      Recent studies suggest that alterations in the processing of amyloid precursor
      protein (APP), resulting in the accumulation of amyloid-beta protein (Abeta) and
      the formation of oligomers leads to synaptic damage and neurodegeneration.
      Therefore, strategies for treatment development have been focused on reducing
      Abeta accumulation using, among other approaches, antiaggregation molecules,
      regulators of the APP proteolysis and processing, reducing APP production (e.g.,
      small-interfering RNA), and increasing Abeta clearance with antibodies,
      apolipoprotein E and Abeta-degrading enzymes (e.g., neprilysin). The main focus
      of this review is on novel treatments for AD with a special emphasis on
      delivering neuroprotective and antiamyloidogenic molecules by gene therapy and by
      promoting neurogenesis.

PMID- 18034652
TI  - Infliximab therapy for pediatric Crohn's disease.
AB  - Crohn's disease (CD) is a chronic inflammatory disease that may involve any part
      of the gastrointestinal tract, characterized by transmural intestinal lesion in a
      genetically susceptible host. Anti-TNF-alpha neutralising agent, infliximab, the
      chimeric monoclonal IgG1 antibody, is indicated for pediatric patients with CD
      and medically refractory luminal and fistulising disease. The present clinical
      practice for infliximab use is induction sequence of 5 mg/kg at 0, 2 and 6 weeks
      administered intravenously and followed by infusion every 8 weeks thereafter.
      Careful attention should be paid to the potential adverse events, especially
      infections and malignancy. Recently, fatal cases in young patients with
      hepatosplenic T-cell lymphoma treated with infliximab and concomitant purine
      analogs were reported. In this review the authors summarize the present knowledge
      of infliximab therapy in children with CD based on the available published
      literature.

PMID- 18034653
TI  - Prevention of childhood rotavirus disease through the use of Rotarix and RotaTeq
      vaccines.
AB  - Rotaviruses are the most common enteric pathogens to cause acute diarrhoea in
      infants and young children throughout the world. Two new live, orally
      administered vaccines (Rotarix and RotaTeq) that provide protection against
      rotavirus infections are now available and have been licensed in many countries
      in Europe, North and Latin America. Two recent large clinical trials have
      demonstrated that their efficacy, immunogenicity and safety, including absence of
      vaccine-associated intussusception in young infants, are remarkably similar. The
      protection against severe rotavirus gastroenteritis extends into the second year
      of follow up for both vaccines. Rotarix and RotaTeq vaccines can be
      coadministered with routine childhood vaccines. However, more data on the
      efficacy of these two new vaccines in low-income nations are needed, particularly
      in Asia and Africa, before global inclusion of rotavirus vaccines into national
      immunisation programmes can be recommended.

PMID- 18034654
TI  - GVAX: an allogeneic, whole-cell, GM-CSF-secreting cellular immunotherapy for the
      treatment of prostate cancer.
AB  - Antitumor vaccines, also known as active immunotherapies, have become an intense
      focus of research over the last decade as a means to ideally provide new
      targeted, and less toxic, therapies to patients with a variety of malignancies.
      Prostate cancer is among the diseases where a large amount of promising data has
      been accumulating regarding several distinct active immunotherapies. Here the
      authors review one of the therapies, known as GVAX, which is among the furthest
      along in clinical evaluation. The authors review the preclinical studies leading
      to the development of this immunotherapy, describe the results from clinical
      trials conducted in patients with prostate cancer, and discuss the benefits,
      limitations and potential future applications of this technology.

PMID- 18034655
TI  - Epitope-based vaccine against influenza.
AB  - The currently available vaccines against influenza are viral strain specific and,
      hence, their efficacy is limited when the circulating strain is not the one
      included in them. We review herewith some of the more recently developed
      influenza vaccines and further describe our own data on the design of epitope
      based broad-spectrum vaccine for human use. This vaccine is comprised of
      recombinant flagella that act as a carrier and adjuvant, expressing conserved
      epitopes of influenza proteins. These epitopes are common to the vast majority of
      influenza virus strains regardless of their antigenic drifts and shifts. The
      vaccine, activating both the humoral and cellular arms of the immune response,
      induces long-lasting protection against many strains of the influenza virus.
      Consequently, it is expected to protect against future strains as well.

PMID- 18034657
TI  - Animal models of anxiety in mice.
AB  - Among the multiple possibilities to study human pathologies, animal models remain
      one of the most used pathways. They allow to access to unavailable answers in
      human patients and to learn about mechanisms of action of drugs. Primarily
      developed with rats, animal models in anxiety have been adapted with a mixed
      success for mice, an easy-to-use mammal with better genetic possibilities than
      rats. In this review, we have focused on the most used animal models in anxiety
      in mice. Both conditioned and unconditioned models are described, to represent
      all types of animal models of anxiety. Behavioural studies require strong care
      for variable parameters, linked to environment, handling or paradigm; we have
      discussed about this topic. Finally, we focused on the consequences of re
      exposure to the apparatus. Test-retest procedures can bring in new answers, but
      should be deeply studied, to revalidate the whole paradigm as an animal model of
      anxiety.

PMID- 18034656
TI  - Development of biologicals for the therapy of lupus erythematosus.
AB  - Lupus erythematosus is a chronic autoimmune inflammatory disease with largely
      unknown etiopathogenesis and no known cure. However, key steps in its
      pathophysiology have been recognized and targeted by specific therapeutic
      techniques. Human patients and murine models of lupus erythematosus manifest a
      wide range of immunological abnormalities. Therapeutic antibodies, which affect
      the activation of potentially autoreactive B cells, have been developed and are
      being tested in clinical trials. Preclinical studies have provided proof of
      concept for the feasibility and efficacy of gene therapy in human lupus
      erythematosus. In this article, we briefly review the clinical characteristics
      and immunological abnormalities of lupus erythematosus and summarize recent
      studies on the use of therapeutic antibodies and gene therapy for the management
      of human lupus erythematosus.

PMID- 18034658
TI  - Possible involvement of GABAergic modulation in the protective effect of
      gabapentin against immobilization stress-induced behavior alterations and
      oxidative damage in mice.
AB  - INTRODUCTION: Acute stress may be experienced in response to an immediate
      physical, emotional or psychological stimulus. Stress has been known to affect
      several brain activities and promote long-term changes in multiple neural
      systems. In the present study, we investigated the possible involvement of
      GABAergic modulation in the protective effect of gabapentin in acute
      immobilization-induced behavioral alterations and oxidative damage in mice.
      MATERIALS AND METHODS: Mice were immobilized for periods of 6 h. Animals were
      divided into different groups, consisting of six in each. Various GABAergic
      modulators were administered either alone or in their combinations, 30 min before
      subjecting the animals for immobilization stress. Various behavioral tests
      (mirror chamber, actophotometer) followed by oxidative parameters
      (malondialdehyde level, glutathione, catalase, nitrite and protein) were assessed
      in animals. RESULTS: Six hours acute immobilization stress caused significant
      locomotor impairment, anxiety-like behavior in mice. Biochemical analyses also
      revealed an increase malondialdehyde, nitrite level and depletion of glutathione
      and catalase activity in 6 h stressed brains. Pretreatment with gabapentin (50
      and 100 mg/kg, i.p.) significantly improved ambulatory movements, anti-anxiety
      effect (decreased time latency to enter in mirror chamber, increased number of
      entries and duration in mirror chamber) and antioxidative activity in stressed
      mice (P < 0.05). Further, picrotoxin (1.0 mg/kg) blocked and muscimol (0.05
      mg/kg) potentiated the protective action of gabapentin (50 mg/kg). Results of
      both behavior as well as biochemical alterations in combination studies were
      significant as compared to their effect per se (P < 0.05). CONCLUSION: Results of
      present study suggest GABAergic modulation might be involved in the protective
      effect of gabapentin against immobilization-induced behavior alteration and
      oxidative damage in mice.

PMID- 18034659
TI  - Systemic administration of adenosine ameliorates pentylenetetrazol-induced
      chemical kindling and secondary behavioural and biochemical changes in mice.
AB  - Adenosine is one of the inhibitory neuromodulators in the brain and is considered
      to be responsible for seizure arrest and postictal refractoriness. Adenosine,
      adenosine receptor agonists, and adenosine uptake blockers are known to reduce
      the severity and duration of amygdala-kindled seizures. The present study was
      carried out to elucidate the anticonvulsant and neuromodulatory effect of
      systemic adenosine on the pentylenetetrazol (PTZ)-induced chemical kindling in
      mice. Kindling was induced by chronic administration of a subconvulsive dose of
      PTZ (40 mg/kg, i.p.) on every other day for a total period of 9 days. Adenosine
      was administered daily, 30 min before PTZ or vehicle. The kindling score was
      recorded immediately following PTZ administration according to a prevalidated
      scoring scale. Various behavioral and biochemical estimations were performed on
      day 10 (i.e. 24 h after the last dose of PTZ). Chronic PTZ treatment
      progressively increased the seizure score with the maximum score reached on day
      9. Behavioral analysis found hyperlocomotor activity, anxiogenic response,
      hyperalgesia and amnesia in kindled mice. Biochemical analysis revealed that
      chronic treatment with PTZ significantly increased lipid peroxidation
      (malondialdehyde levels), nitrite (NO(2-) levels), adenosine deaminase (ADA) and
      total RNA levels and decreased catalase, reduced glutathione (GSH) levels in
      brain homogenates, and a depletion of adrenal ascorbic acid. Daily treatment with
      adenosine (25 and 50 mg/kg, i.p.) for 9 days led to a significant decrease in PTZ
      induced kindling score and also reversed various behavioral and biochemical
      alterations produced by PTZ. The results of the present study suggested that
      systemic adenosine administration reversed the behavioral and biochemical
      alterations induced by chronic PTZ.

PMID- 18034660
TI  - The mechanisms of vasorelaxant effect of leptin on isolated rabbit aorta.
AB  - In the present study, we analysed the effects of leptin on rabbit aorta and the
      mechanisms underlying these effects. Leptin (10(-12)-10(-9) m) induced
      concentration-dependent relaxation in intact rabbit aorta rings precontracted
      with phenylephrine (10(-6) m). Removal of endothelium abolished the effects of
      leptin. Pretreatment of rings with N(omega)-nitro-l-arginine methyl ester (10(-4)
      m 20 min) or catalase (1200 U/mL 20 min) significantly reduced the relaxant
      response to leptin when compared with the control group. The incubation of
      brefeldin A (3.5 x 10(-5) m 90 min), indomethacin (10(-5) m 20 min),
      tetraethylammonium (10(-4) m 20 min), and glibenclamide (10(-5) m, 20 min) did
      not affect the leptin-induced vasodilation. These results suggest that leptin
      relaxes the rabbit aorta. The relaxation is mediated by endothelium-derived
      nitric oxide and hydrogen peroxide.

PMID- 18034661
TI  - Hypolipidemic and antioxidant effects of ethanolic extract from dried calyx of
      Hibiscus sabdariffa in alloxan-induced diabetic rats.
AB  - The present study investigated the hypolipidemic and antioxidant effects of
      ethanolic extract of Hibiscus sabdariffa L (HSE) in rats treated with alloxan.
      The results were compared with the standard hypolipidemic drug lovastatin. HSE at
      doses of 100 and 200 mg/kg elicited dose-dependent effects on the biomarkers
      evaluated. In alloxan-treated rats, HSE at the dose of 200 mg/kg significantly
      attenuated the elevated blood glucose concentration by 57%. Lovastatin (10 mg/kg)
      similarly reduced the glucose level in alloxan-treated rats by 48%. HSE reduced
      the alloxan-induced increases in cholesterol, very low-density lipoprotein
      cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C) and atherogenic
      index by 29%, 36%, 40%, and 32%, respectively while lovastatin decreased the
      alloxan-induced increases in the parameters by 25%, 23%, 28%, and 31%,
      respectively. HSE (200 mg/kg) and lovastatin (P < 0.01) decreased the alloxan
      induced increases in the lipid profiles both in the liver and the kidneys. HSE at
      200 mg/kg attenuated the alloxan-induced decrease in the activities of superoxide
      dismutase (SOD), catalase (CAT) and the level of glutathione (GSH) by 36%, 44%,
      and 64% in the liver and by 20%, 43%, and 85% in the kidney of rats. Lovastatin
      similarly increased SOD, CAT and GSH by 32%, 29%, and 64% in the liver and by
      17%, 26%, and 73% in the kidney of alloxan-treated rats. HSE (200 mg/kg)
      significantly decreased the alloxan-mediated increase in malondialdehyde (MDA)
      and protein carbonyl (PC) levels in the liver by 44% and 43% and in the kidneys
      by 45% and 38%, respectively, while lovastatin decreased the alloxan-induced
      elevation in MDA and PC in the liver by 42% and 41% and in the kidney by 45% and
      33%, respectively. While HSE at a dose of 200 mg/kg and lovastatin normalized the
      activity of phosphatidate phosphohydrolase in the liver, the extract and
      lovastatin did not elicit significant changes in the kidney enzyme activity in
      rats treated with alloxan. Overall, our data demonstrate that HSE possesses
      strong hypolipidemic as well as antioxidant properties in alloxan-induced
      diabetic rats and as such Hibiscus sabdariffa could be useful in preventing the
      development of atherosclerosis and possible related cardiovascular pathologies
      associated with diabetes.

PMID- 18034662
TI  - Effects of L-arginine and phosphodiesterase-5 inhibitor, sildenafil, on
      inflammation and airway responsiveness of sensitized BP2 mice.
AB  - Nitric oxide (NO) levels are elevated in the exhaled breath of asthmatic patients
      and NO is considered as a biomarker of airway inflammation. However, the
      functions of NO in the airways are not completely understood. L-arginine, as the
      substrate of NO synthases, is the precursor of NO which stimulates guanylate
      cyclase and leads to the formation of cyclic GMP (cGMP). Sildenafil, a
      phosphodiesterase-5 (PDE-5) inhibitor, prevents the degradation of cGMP. In this
      study the effects of L-arginine and sildenafil treatment, alone or in
      combination, were evaluated in ovalbumin-sensitized BP2 mice. These effects
      concerning the airway responsiveness to inhaled methacholine (MCh) were evaluated
      by whole-body plethysmography (WBP), the inflammatory response evaluated by
      bronchoalveolar lavage fluid (BALF) analyses and lung tissue biopsies
      (eosinophilic inflammation associated with lung remodelling), and NO metabolite
      measurements (by Griess reaction) in BALF. Ovalbumin sensitization induced: (a)
      an inflammatory reaction with eosinophil and neutrophil influx in BALF and lung;
      and (b) an increased bronchial responsiveness to MCh. L-arginine treatment [50
      mg/kg intraperitoneally (i.p.), for 7 days] increased the relative amount of
      eosinophils and neutrophils in BALF, had a tendency to increase the airway
      responsiveness to inhaled MCh and increased the NO metabolite level in BAL.
      Sildenafil treatment (20 mg/kg i.p. for 7 days) did not affect the airway
      responsiveness to MCh and had a lower effect compared with L-arginine on
      inflammatory reactions. The combination of the two treatments resulted in a
      dramatic enhancement of the airway responsiveness to inhaled MCh. The relative
      amount of eosinophils was increased and lung histology showed obvious worsened
      tissular lesions such as epithelial shedding and hypertrophy, hyperplasia of
      smooth muscle cells, and fibrosis. These findings are consistent with the notion
      that NO production plays a role in the development of airway inflammation and
      hyperresponsiveness of sensitized mice and highlighted the potential risk of the
      L-arginine dietary complement or PDE5 treatment in asthmatic patients.

PMID- 18034663
TI  - Dose-response effect of ellagic acid on circulatory antioxidants and lipids
      during alcohol-induced toxicity in experimental rats.
AB  - Ellagic acid (EA) is a naturally occurring polyphenolic compound that exhibits
      antioxidative, anti-inflammatory, anti-hyperlipidaemic and anticarcinogenic
      activities in a wide range of assays both in vitro and in vivo. It occurs in
      various foods such as strawberries, grapes, walnuts, etc. The aim of this study
      was to assess the effect of ellagic acid on alcohol-induced changes in the
      circulatory antioxidative status, micronutrients and lipid levels in a dose
      dependent fashion. Female albino Wistar rats weighing 150-170 g were used to
      assess the effects of EA against alcohol-induced damage. Three different
      concentrations of EA (30, 60 and 90 mg/kg body weight) were tested against 20%
      alcohol via intragastric administration. At the end of the experimental duration
      of 45 days, we evaluated endogenous antioxidants: both enzymatic (superoxide
      dismutase, catalase and glutathione peroxidase) and non-enzymatic (vitamin C and
      E, and reduced glutathione) status, micronutrients, viz. copper and zinc, and
      lipids: cholesterol, triglycerides, free fatty acids and phospholipids in the
      circulation. The body weight gain of both alcohol-fed rats and EA-treated rats
      were also inferred. EA significantly inhibits alcohol-induced toxicity by
      improving body weight, restoring antioxidant status, modulating micronutrients
      and attenuating the lipid levels in the circulation. The greatest inhibitory
      effect was observed with 60 mg/kg body weight of EA in all the biochemical
      assessments. The results support the hypothesis that EA at the concentration of
      60 mg/kg body weight decreases the intensity of alcohol-induced toxicity and
      could be developed as a potential drug for alcohol abuse in the near future.

PMID- 18034664
TI  - Evaluation of two evidence-based knowledge transfer interventions for physicians.
      A cluster randomized controlled factorial design trial: the CardioDAS Study.
AB  - To investigate the potential benefits of two modes of evidence-based knowledge
      transfer ('active' and 'passive' modes) in terms of improvement of intention of
      prescription, knowledge, and real prescription in practice, we performed an open
      randomized controlled trial (CardioDAS) using a factorial design (two tested
      interventions: 'active' and 'passive' knowledge transfer) and a hierarchical
      structure (cluster of physicians for each department level). The participants
      were cardiologists working in French public hospitals. In the 'passive' transfer
      group, cardiologists received evidence-based knowledge material (available on
      Internet) every week for a duration of 1 year. In the 'active' transfer group,
      two knowledge brokers (EA, PN) visited the participating departments (every 2
      months for 1 year, 2 h per visit). The primary outcome consisted in the adjusted
      absolute mean variation of score (difference between post- and pre-study session)
      of answers to simulated cases assessing the intention to prescribe. Secondary
      outcomes were the variation of answers to a multiple-choice questionnaire (MCQ)
      assessing knowledge and of the conformity of real prescriptions to evidence-based
      reference assessing the behavioral change. Twenty-two French units (departments)
      of cardiology were randomized (72 participating cardiologists). In the 'active'
      transfer group, the primary outcome was more improved than that in the control (P
      = 0.031 at the department level, absolute mean improvement of 5 points/100). The
      change in knowledge transfer (MCQ) was also significant (P = 0.039 at the
      department level, absolute mean improvement of 6 points/100). However, no benefit
      was shown in terms of prescription conformity to evidence. For the 'passive' mode
      of knowledge transfer and for the three outcomes considered, no improvement was
      identified. CardioDAS findings confirm that 'active' knowledge transfer has some
      impact on participants' intent to prescribe and knowledge, but no effect on
      behavioral outcome. 'Passive' transfer seems far less efficient. In addition, the
      size of the benefit remains small and its consequences limited in practice.

PMID- 18034665
TI  - Association between antipsychotic drugs, antidepressant drugs and venous
      thromboembolism: results from the EDITH case-control study.
AB  - Cohort studies suggest that exposure to antipsychotic agents may be associated
      with an increased risk of venous thromboembolism (VTE). Few data concerning
      antidepressant drugs are available. Using a different methodological approach,
      the aim of this study was to estimate the association between neuroleptic and
      antidepressant drug use and the risk of VTE. We report the results of a case
      control study designed to evaluate interactions between acquired and inherited
      risk factors of VTE. We included 677 cases hospitalized with deep vein thrombosis
      and or pulmonary embolism with no major acquired risk factor for VTE, and 677
      controls matched for gender and age. Drug exposure was defined as current use of
      drugs at admission. Neuroleptic exposure was associated with an increased risk of
      VTE (OR = 2.1, 95% CI 1.4-3.2). Among neuroleptics, antipsychotic agent use was
      associated with a 3.5-fold increased risk of VTE (OR = 3.5, 95% CI 2.0-6.2). No
      association was found between antidepressant drug exposure and the risk of VTE
      (OR = 1.1, 95% CI 0.9-1.5). In this hospital-based case-control study, exposure
      to antipsychotic drugs was associated with an increased risk of VTE. These
      results, added to previous results, suggest that clinicians should consider
      antipsychotic drug exposure as a potential risk factor of VTE. More studies are
      needed in order to further elucidate this adverse effect, and to determine the
      possible predisposing factors and the biological mechanisms involved.

PMID- 18034666
TI  - Effect of voriconazole on the pharmacokinetics of diclofenac.
AB  - The nonsteroidal anti-inflammatory drug diclofenac is extensively metabolized by
      cytochrome P450 (CYP) enzymes, mainly by CYP2C9. Our objective was to study the
      effect of voriconazole, a potent inhibitor of several CYP enzymes, on the
      pharmacokinetics of diclofenac. This study had a two-way, open, crossover design
      and included 10 healthy Caucasian male subjects. In the control phase, the
      subjects ingested a single 50-mg oral dose of diclofenac. In the voriconazole
      phase, the subjects ingested voriconazole 400 mg twice daily on the first day and
      200 mg twice daily on the second day, and 50 mg diclofenac was given 1 h after
      the last dose of voriconazole. Plasma diclofenac concentrations were determined
      for up to 24 h post-dose. In the voriconazole phase, the area under the plasma
      concentration-time curve of diclofenac was 178% (95% CI 143-212%; P < 0.001) and
      the peak plasma concentration was 214% (95% CI 128-300%; P < 0.05) of the
      respective control value. Voriconazole did not affect significantly the
      elimination half-life or time to maximum concentration of diclofenac. The renal
      clearance of diclofenac was decreased by 47% (95% CI -76% to -16%; P < 0.01) by
      voriconazole. In conclusion, voriconazole increased exposure to diclofenac,
      probably mainly by inhibition of its cytochrome P450 (CYP)-mediated metabolism.
      The inhibition of CYP2C9, and to some extent that of CYP3A4 and CYP2C19 enzymes
      during the first-pass metabolism of diclofenac seems to be involved in the
      interaction. The clinical importance of the interaction between voriconazole and
      diclofenac remains to be studied, but lower doses of diclofenac may be adequate
      for patients receiving voriconazole.

PMID- 18034667
TI  - Orofacial dyskinesia associated with tiemonium.
AB  - Tiemonium, an anti-spasmodic drug, can have adverse effects related to its anti
      muscarinic effect. Dyskinesia is described with other anti-cholinergic drugs, but
      there are no reports of dyskinesia associated with tiemonium. We report a
      reversible orofacial dyskinesia following tiemonium intake (contained in
      Visceralgine forte) in a woman with positive rechallenge. She presented these
      symptoms two times after two separate injections with an interval of 2 months.
      The case was reported to the Tunisian Centre of Pharmacovigilance.

PMID- 18034668
TI  - Analysis of drug transporter expression in human intestinal Caco-2 cells by real
      time PCR.
AB  - Expression of drug transporters corresponds to a crucial parameter in intestinal
      Caco-2 cells widely used for investigating drug absorption. In order to
      characterize it in an accurate, reproducible and comparative manner, we analyzed
      mRNA levels of 19 influx and efflux drug transporters through real-time
      quantitative polymerase chain reaction assays combined with the use of a total
      RNA reference standard. Profiles of transporter expression were found to be
      significantly correlated in two independent Caco-2 cell clones and in human small
      intestine, which may support the use of Caco-2 cells for investigating intestinal
      drug transport. Several transporters were nevertheless quantitatively expressed
      at higher (MRP2, MRP3, MRP4, MRP5, MRP6, OATP-A, OATP-B, OCT1 and MCT1) or lower
      (BCRP) levels in Caco-2 cells comparatively to small intestine. Moreover, MDR1,
      MRP2, OATP-A and PEPT1 mRNA relative expression were found to differ in the two
      analyzed Caco-2 cell clones by at least a twofold factor, highlighting that some
      variations in transporter expression may occur in Caco-2 cells depending on cell
      origin, and therefore underlining the interest of carefully characterizing
      transporter levels in any Caco-2 cell clone before its use for drug transport
      assays.

PMID- 18034669
TI  - Influence of tetrahydrocurcumin on tail tendon collagen contents and its
      properties in rats with streptozotocin-nicotinamide-induced type 2 diabetes.
AB  - Changes in the structural and functional properties of collagen caused by
      advanced glycation might be of importance for the etiology of late-stage
      complications in diabetics. Curcumin is the most active component of turmeric. It
      is believed that curcumin is a potent antioxidant and anti-inflammatory agent.
      Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin, exhibiting
      many of the same physiological and pharmacological activities of curcumin and in
      some systems may exert greater antioxidant activity than curcumin. In diabetic
      rats, hydroxyproline and collagen content as well as its degree of cross-linking
      were increased, as shown by increased extent of glycation, collagen-linked
      fluorescence, neutral salt collagen, and decreased acid and pepsin solubility.
      Administration of THC for 45 days to diabetic rats significantly reduced the
      accumulation and cross-linking of collagen. The effects of THC were comparable
      with those of curcumin. In conclusion, administration of THC had a positive
      influence on the content of collagen and its properties in streptozotocin- and
      nicotinamide-induced diabetic rats. THC was found to be more effective than
      curcumin.

PMID- 18034671
TI  - A global perspective on changes in the burden of caries and periodontitis:
      implications for dentistry.
AB  - The structure and contents of most oral health care systems and the contents of
      dental curricula reflect a deep-rooted tradition for attempting to cure oral
      diseases by refined technological means. However, better oral health conditions
      for the world's populations necessitate the application of up-to-date scientific
      knowledge to control the major oral diseases. This review points out that not
      only should the structure and contents of oral health care delivery systems be
      based on state-of-the-art knowledge about the biology of the oral diseases; they
      must also take into account the trends for change in caries and periodontal
      diseases within and between populations, and acknowledge the impact of changes in
      treatment philosophies for these trends. The oral disease profiles for
      populations in low- and high-income countries are briefly described, and it is
      concluded that the rapidly changing disease profiles observed in high-income
      countries necessitate re-thinking of the future role and organization of
      dentistry in such countries. The priorities for low- and middle-income countries
      must be to avoid repeating the mistakes made in the high-income countries.
      Instead, these societies might take advantage of setting priorities based on a
      population-based common risk factor approach. If such an approach is adopted, the
      training of personnel with oral health care competence must be rethought. The
      authors suggest three different cadres of dental care providers to be considered
      for an approach that allows health care planners in different populations around
      the world to prioritize appropriate oral health care with due respect for the
      socio-economic conditions prevailing.

PMID- 18034672
TI  - Minimum requirements for new dental materials.
AB  - A brief review of the development of standards for testing and certification of
      dental materials is presented. The tests employed in the standards are not
      correlated for the clinical use of the materials, nor to the reasons for failures
      of the materials. They are, therefore, of limited value for the selection of
      materials to be used in practice but they are important for quality control of
      the manufacture of the materials. Previous certification programmes are being
      discontinued. The responsibility for selecting safe and efficient materials is
      transferred to the clinicians whereas making safe and efficient materials still
      is the responsibility of the manufacturers.

PMID- 18034673
TI  - Practice-based dental research.
AB  - Practice-based research networks have existed in medicine for many years, but
      they are relatively new in dentistry. Practice-based dental research is carried
      out in the 'real world' setting of dental practice. It encounters many problems,
      especially related to the clinicians' treatment decisions and their variations in
      assessments of clinical quality. Practice-based dental research networks have
      been active in Europe for the last 10-15 years and new practice-based dental
      research networks have recently been funded in the USA. They have been charged
      with the establishment of networks to carry out short-term clinical studies that
      have been proposed by clinicians to solve the problems they encounter in daily
      clinical practice. Data sharing and communication within and among the networks
      and with the dental community at large are a primary goal to become successful
      and optimally serve dental practice. A secondary goal is to conduct chart reviews
      on disease and treatment patterns and obtain estimates of the prevalence of less
      common conditions. An outline of a possible establishment of a research network
      is presented and the potential to institute a programme for practice-based
      testing of dental materials and procedures is suggested.

PMID- 18034674
TI  - Dental restorations for oral rehabilitation - testing of laboratory properties
      versus clinical performance for clinical decision making.
AB  - At the outset, the categories of physical, chemical, mechanical, biological and
      clinical properties of biomaterials are reviewed in terms of their definitions
      and relevant examples. Clinical performance for restorative materials is
      considered in terms of five crucial categories of factors (operator, design,
      materials, site and patient). Clinical performance assessment in actual clinical
      trials is described in terms of United States Public Health Service (USPHS) and
      modified USPHS categories of ratings collected from direct observations. Clinical
      failure analysis is characterized using reverse s-shaped curves to summarize
      longevity (failure or success) and clinical longevity for 50% failures (CL(50))
      is defined. Actual practice effectiveness is demonstrated as being approximately
      one-half of clinical trial efficacy. Types of restorative dental material
      clinical trials are contrasted (longitudinal versus cross-sectional, short-term
      versus long-term, university-based versus practice-based research networks). Poor
      correlations between laboratory test values and clinical performance are
      explained. The need for risk assessment is emphasized. Evidence-based dentistry
      is defined in terms of available published information and precautions. At this
      point, the evidence base for clinical performance of biomaterials is scant.

PMID- 18034675
TI  - Biological tooth replacement and repair.
AB  - Implantology is an ancient art that can be traced back several thousand years.
      Although modern implants have improved substantially over the last 50 years, the
      basic principle remains unchanged: replace a missing tooth with an inert non
      biological material (metal, ceramic etc.). The rate of technological improvements
      in implants has reached a plateau and substantial new developments will require
      major changes to the basic approach. Rapid advances in the development of cell
      based therapies in medicine suggest that similar approaches should be considered
      in dental treatment. The use of cell-based implants that will develop into
      natural teeth and the employment of cells to restore/repair caries lesions is
      thus an area of considerable interest and excitement.

PMID- 18034678
TI  - Morphogenesis of koi herpesvirus observed by electron microscopy.
AB  - Koi herpesvirus (KHV or cyprinid herpesvirus 3) was inoculated onto three fish
      cell lines derived from carp, Cyprinus carpio L., and the process of virion
      formation observed with electron microscopy. Essentially, similar features of
      virus particles were observed in all three cell lines. The nucleus of infected
      cells was characterized by margination of chromatin and often contained many
      capsids of about 110 nm in diameter with varying morphology. The morphological
      variation of the capsids was very similar to that of mammalian herpesviruses.
      Some capsids protruded from the inner nuclear membrane, and others, with
      envelopes, were located in the perinuclear space between the inner and outer
      nuclear membrane, suggesting budding of capsids at the inner nuclear membrane.
      Naked capsids and envelopment of capsids by budding into vesicles were also
      observed in the cytoplasm. Mature, enveloped virions 170-200 nm in diameter were
      seen in cytoplasmic vesicles or outside the cell. These observations suggest KHV
      virions mature through a complex morphological pathway including two distinct
      envelopments, which have been found only in herpesviruses. These observations
      support the inclusion of KHV in the family Herpesviridae.

PMID- 18034677
TI  - Clinical and inflammatory effects of galvano-ceramic and metal-ceramic crowns on
      periodontal tissues.
AB  - Prosthetic crowns made by galvano-forming are considered to be highly
      biocompatible and aesthetic restorations. Therefore, they represent an
      alternative crown-system to conventional metal-ceramic crowns in replacing lost
      tooth structure. However, there are few data available on clinical and
      biochemical effects of galvano-ceramic crowns on periodontal tissues. The purpose
      of this controlled study was to test the impact of galvano-ceramic crowns and
      metal-ceramic crowns on clinical and inflammatory responses of periodontal
      tissues. A prospective, blinded randomized clinical trial was conducted. Galvano
      ceramic crowns and metal-ceramic crowns were placed in 52 periodontally healthy
      patients in split-mouth design. Clinical parameters (gingival index, plaque
      index, probing depths and recessions) were recorded from six sites per tooth.
      Initial tissue alteration was accessed analysing the gingival crevicular fluid
      flow rate and IgG concentration in gingival crevicular fluid. After 24 months, 34
      patients could be re-evaluated. All crowns were in adequate function and obvious
      clinical inflammation was rarely observed. After 24 months of follow-up, gingival
      tissues adjacent to galvano-ceramic crowns showed significantly less signs of
      clinical and inflammatory responses according to plaque index (P = 0.004),
      gingival index (P < 0.001), gingival crevicular fluid flow rate (P = 0.012) and
      IgG (P = 0.002). Data were also analyzed for buccal and oral sites separately.
      Gingival tissues adjacent to metal-ceramic crowns showed significantly increased
      clinical and inflammatory values for plaque index (P = 0.005), gingival index (P
      = 0.008), gingival crevicular fluid flow rate (P = 0.006), IgG (P = 0.007) at
      oral sites compared to galvano-ceramic crowns. Our data suggest a stabilizing
      effect of galvano-ceramic crowns on periodontal tissues over time.

PMID- 18034679
TI  - Field validation of experimental challenge models for IPN vaccines.
AB  - Atlantic salmon S1/2 pre-smolts from the VESO Vikan hatchery were assigned to
      study groups, i.p. immunized with commercially available, multivalent oil
      adjuvanted vaccines with (Norvax Compact 6 - NC-6) or without (Norvax Compact 4 -
      NC-4) recombinant infectious pancreatic necrosis virus (IPNV) antigen. A control
      group received saline solution. When ready for sea, the fish were transported to
      the VESO Vikan experimental laboratory, where two identical tanks were stocked
      with 75 fish per group before being transferred to 10 degrees C sea water and
      exposed by bath to first passage IPNV grown in CHSE-214 cells. The third tank
      containing 40 fish from each group was challenged by the introduction of 116 fish
      that had received an i.p injection of IPNV-challenge material. The remaining
      vaccinated fish were transported to the VESO Vikan marine field trial site and
      placed in two identical pens, each containing approximately 53 000 fish from the
      NC-6 group and 9000 fish from the NC-4 group. In the experimental bath challenge
      trial, the cumulative mortality was 75% and 78% in the control groups, and the
      relative percentage survival (RPS) of the NC-6-immunized fish vs. the reference
      vaccine groups was 60% and 82%, respectively. In the cohabitation challenge, the
      control mortality reached 74% and the IPNV-specific vaccine RPS was 72%. In both
      models, the reference vaccine lacking IPNV antigen gave a moderate but
      statistically significant non-specific protection. In the field, a natural
      outbreak of infectious pancreatic necrosis (IPN) occurred after 7 weeks lasting
      for approximately 3.5 months before problems due to winter ulcers became
      dominating. During this outbreak, mortality in the NC-4 groups were 33.5% and
      31.6%, respectively, whereas mortality in the NC-6 groups were 6.9% and 5.3%,
      respectively, amounting to 81% IPNV-specific protection. In conclusion, the IPN
      protection estimates obtained by experimental challenges were consistent between
      tanks, and were confirmed by the field results.

PMID- 18034680
TI  - Microhabitat selection of Gyrodactylus salaris Malmberg on different salmonids.
AB  - The microhabitat selection of the ectoparasite Gyrodactylus salaris (Laerdalselva
      strain, Norway) was investigated concurrently with studies on the parasite
      population growth on five strains of Atlantic salmon, Salmo salar L., and a
      strain of Danish rainbow trout, Oncorhynchus mykiss (Walbaum). The salmon used
      were hatchery-reared parr of East Atlantic strains [River Conon (Scotland), River
      Stora (western Denmark) and River Atran (western Sweden)] and Baltic strains
      [Lule and Ume (eastern Sweden)]. The location and numbers of parasites were
      recorded on anaesthetized fish once a week from week 0 to week 8. The mean
      abundance of G. salaris steadily increased to high levels on the River Conon,
      Stora and Atran strains until the end of the experiment. The mean abundance of G.
      salaris on the two Baltic strains (River Lule alv and River Ume alv) initially
      increased but after 4-7 weeks the growth of the parasite infrapopulations
      decreased markedly. The Danish rainbow trout strain showed the lowest abundances
      of all the fish species and strains. Gyrodactylus salaris preferentially selected
      the fins and head region when colonising the hosts (all species and strains).
      Increasing percentages of G. salaris on the tail fins of the East Atlantic
      strains and rainbow trout were found during the course of infection, whereas the
      two Baltic salmon strains experienced a decreasing percentage of parasites in
      this microhabitat.

PMID- 18034681
TI  - Spinal deformation in commercially cultured Atlantic salmon, Salmo salar L.: a
      clinical and radiological study.
AB  - A clinical and radiographic study was carried out on 2016 randomly selected
      Atlantic salmon parr from six farms, which weighed between 55 and 100 g. In
      addition, 86 fish from six marine farms were similarly studied. Radiographically
      detectable vertebral lesions were found in 3.8-8.8% of the parr. The changes
      ranged from a single vertebra showing features, such as demineralization,
      increased density and slight loss of structure, to fish with multiple vertebrae
      affected by collapse, fusion and change in intervertebral space that could give
      rise to lordosis or kyphosis or abnormal vertebrae at several locations. The
      predominant location was the vertebral region V21-27, and rarely V44 caudad. The
      radiographic changes in seawater salmon mirrored those found in parr, but
      vertebrae V35 caudad were more frequently involved. Very few parr were found to
      have abnormal vertebrae in the peduncle area which suggests that the development
      of lesions at this location occurs de novo in the seawater phase, given that
      'stumpy' fish are most frequent reported deformity at slaughter. It was concluded
      that minor vertebral change could be detected radiographically in many parr with
      no observable effect on external morphology. Whether such minor radiographic
      alteration would proceed to observable morphological change at slaughter weight
      is open to question.

PMID- 18034682
TI  - The aetiology of spinal deformity in Atlantic salmon, Salmo salar L.: influence
      of genetic factors on the frequency and severity in freshwater stages.
AB  - A radiographic study was carried out on 2-year groups of pre-smolt parr to detect
      the comparative frequency of vertebral change in a range of defined pedigreed
      families of high growth rate of Atlantic salmon, Salmo salar L., reared under
      identical conditions. The observed frequency of deformity was related to the
      observed deformity level in the seawater parental generation, and to a
      potentially uncontrolled environmental determinant, i.e. stripping date. High and
      low parental deformity groups of families were found to produce offspring that
      had very similar levels of radiographically detectable spinal deformities in the
      pre-smolt parr, suggesting no genetic link. With regard to stripping date, the
      overall incidence was nearly half that seen in the preceding year (8.7% cf
      16.6%). However, a non-significant trend to fewer radiographic spinal deformities
      was seen in the later stripping period.

PMID- 18034683
TI  - The aetiology of spinal deformity in Atlantic salmon, Salmo salar L.: influence
      of different commercial diets on the incidence and severity of the preclinical
      condition in salmon parr under two contrasting husbandry regimes.
AB  - A large-scale trial of the effect of different commercial diets on the incidence
      of preclinical spinal deformation, as assessed by radiography, and the influence
      of two contrasting rearing systems was carried out. Two sets of three populations
      of Atlantic salmon, each of 20 000 first feeding fry of identical hatchery
      origin, created from equal numbers of eggs from 15 different families, were
      reared under commercial conditions on two different farms. Three commercial
      (closed formula) extruded fish meal-based diets were used in this study (diets A,
      B & C). Each diet was fed to one population of 20 000 fish at each site. Fish
      were fed a percentage of their body weight per day, with feeding rates set at
      commercial levels, based on water temperature, day length and fish biomass.
      Additional hand feeding was used to ensure satiation in all tanks. Fish in each
      tank were bulk-weighed and counted at the beginning and at 2-week intervals
      throughout the study. The fish were grown for 30 weeks. In addition, phosphorus
      (P) digestibility was evaluated by in-feed absorption testing in rainbow trout.
      The morphology of the radiographic lesions conformed to those described
      previously. Statistical analysis using multivariate regression analysis showed
      that date of sampling, site and diet were all statistically significant (P <
      0.001) on univariable analysis. Farm A had significantly more affected fish than
      farm B (P < 0.001), which may have been attributable to variation in dissolved
      oxygen levels. The available dietary P levels were low in each diet. The number
      of fish affected in the group of fish being fed diet B was significantly lower
      than in the groups being fed diets A or C (P < 0.001). It appears most likely
      that the occurrence of preclinical radiographically apparent defects in parr
      which are believed to lead to the condition known as 'spinal deformity' is
      predominantly caused by a deficiency of available dietary P in first-feeding fry.
      The availability of dietary P may also vary considerably between diets formulated
      using different ingredients. Phytate-P associated with plant ingredients may
      affect the availability of P as well as other essential dietary nutrients.
      Additionally, diets for the production of salmonids in fresh water are currently
      formulated to keep P effluent to a minimum compatible with healthy spinal
      development. These various factors combine to make it crucial that small Atlantic
      salmon, especially first-feeding fry, are provided with carefully formulated
      diets fortified to an adequate level with a high quality source of available P.

PMID- 18034684
TI  - QSAR study of Phenoxypyrimidine Derivatives as Potent Inhibitors of p38 Kinase
      using different chemometric tools.
AB  - Selective inhibition of the CSBP/p38 mitogen-activated protein kinase pathway may
      be an attractive target for the development of therapeutic agents to treat
      chronic inflammatory disease. A series of Phenoxypyrimidine Derivatives as Potent
      Inhibitors of p38 Kinase was subjected to quantitative structure-activity
      relationship (QSAR) analysis to find the structural requirements for ligand
      binding. A collection of chemometrics methods including multiple linear
      regression (MLR), factor analysis-based multiple linear regression (FA-MLR),
      principal component regression and partial least squared combined with genetic
      algorithm for variable selection (GA-PLS) were employed to make connections
      between structural parameters and enzyme inhibition. The results revealed the
      significant roles of steric effect, hydrogen bonding and electronic properties on
      the p38 inhibitory activity of the studied molecules. The most significant QSAR
      model, obtained by GA-PLS, could explain and predict 98% and 87% of variances in
      the pIC(50) data, respectively.

PMID- 18034686
TI  - Is the cerebral cortex hyperexcitable or hyperresponsive in migraine?
AB  - Although migraineurs appear in general to be hypersensitive to external stimuli,
      they maybe also have increased daytime sleepiness and complain of fatigue.
      Neurophysiological studies between attacks have shown that for a number of
      different sensory modalities the migrainous brain is characterised by a lack of
      habituation of evoked responses. Whether this is due to increased cortical
      hyperexcitability, possibly due to decreased inhibition, or to an abnormal
      responsivity of the cortex due a decreased preactivation level remains disputed.
      Studies using transcranial magnetic stimulation in particular have yielded
      contradictory results. We will review here the available data on cortical
      excitability obtained with different methodological approaches in patients over
      the migraine cycle. We will show that these data congruently indicate that the
      sensory cortices of migraineurs react excessively to repetitive, but not to
      single, stimuli and that the controversy above hyper- versus hypo-excitability is
      merely a semantic misunderstanding. Describing the migrainous brain as
      'hyperresponsive' would fit most of the available data. Deciphering the precise
      cellular and molecular underpinnings of this hyperresponsivity remains a
      challenge for future research. We propose, as a working hypothesis, that a
      thalamo-cortical dysrhythmia might be the culprit.

PMID- 18034687
TI  - Migraine excitability.

PMID- 18034688
TI  - The brain is hyperexcitable in migraine.
AB  - Migraine is a very common disorder occurring in 20% of women and 6% of men.
      Central neuronal hyperexcitability is proposed to be the putative basis for the
      physiological disturbances in migraine. Since there are no consistent structural
      disturbances in migraine, physiological and psychophysical studies have provided
      insight into the underlying mechanisms. This is a review of the
      neurophysiological studies which have provided an insight to migraine
      pathogenesis supporting the theory of hyperexcitability.

PMID- 18034689
TI  - Cortical excitability and migraine.

PMID- 18034690
TI  - Molecular and cellular events in alcohol-induced muscle disease.
AB  - Alcohol consumption induces a dose-dependent noxious effect on skeletal muscle,
      leading to progressive functional and structural damage of myocytes, with
      concomitant reductions in lean body mass. Nearly half of high-dose chronic
      alcohol consumers develop alcoholic skeletal myopathy. The pathogenic mechanisms
      that lie between alcohol intake and loss of muscle tissue involve multiple
      pathways, making the elucidation of the disease somewhat difficult. This review
      discusses the recent advances in basic and clinical research on the molecular and
      cellular events involved in the development of alcohol-induced muscle disease.
      The main areas of recent research interest on this field are as follows: (i)
      molecular mechanisms in alcohol exposed muscle in the rat model; (ii) gene
      expression changes in alcohol exposed muscle; (iii) the role of trace elements
      and oxidative stress in alcoholic myopathy; and (iv) the role of apoptosis and
      preapoptotic pathways in alcoholic myopathy. These aforementioned areas are
      crucial in understanding the pathogenesis of this disease. For example, there is
      overwhelming evidence that both chronic alcohol ingestion and acute alcohol
      intoxication impair the rate of protein synthesis of myofibrillar proteins, in
      particular, under both postabsorptive and postprandial conditions. Perturbations
      in gene expression are contributory factors to the development of alcoholic
      myopathy, as ethanol-induced alterations are detected in over 400 genes and the
      protein profile (i.e., the proteome) of muscle is also affected. There is
      supportive evidence that oxidative damage is involved in the pathogenesis of
      alcoholic myopathy. Increased lipid peroxidation is related to muscle fibre
      atrophy, and reduced serum levels of some antioxidants may be related to loss of
      muscle mass and muscle strength. Finally, ethanol induces skeletal muscle
      apoptosis and increases both pro- and antiapoptotic regulatory mechanisms.

PMID- 18034691
TI  - Alcoholism, craving, and hormones: the role of leptin, ghrelin, prolactin, and
      the pro-opiomelanocortin system in modulating ethanol intake.
AB  - Evidence is growing that appetite regulating peptides such as leptin and ghrelin,
      but also other hormones including prolactin are altered in alcoholism. The brain
      pro-opiomelanocortin (POMC) system which has important mediating roles in alcohol
      intake also has important functions in prolactin regulation and energy
      homeostasis. Furthermore, it has been demonstrated to be functionally integrated
      with leptin regulation. The satiety factor leptin seems to be counteracted by the
      gut-derived peptide ghrelin which increases hunger and food intake. Consequently,
      the POMC system may have a role in integrating regulation of alcohol effects and
      these seemingly disparate regulatory systems. The goal of this mini-review is to
      discuss the results of some recent investigations of the potential interactions
      of these systems with acute and chronic alcohol responses.

PMID- 18034692
TI  - Acculturation and alcohol among Latino adults in the United States: a
      comprehensive review.
AB  - BACKGROUND: In light of the inconsistent evidence associating acculturation with
      drinking outcomes among Latinos in the United States, the current paper
      comprehensively reviews the literature on this topic. METHODS: Studies were
      eligible for review if they (1) were published in a refereed journal, (2) were
      published in English, (3) sampled Latino/Hispanic adults aged 18+, (4) examined
      self-reported drinking behavior, alcohol-related problems, and/or alcohol
      abuse/dependence, and (5) reported original results or unique analyses from a
      larger dataset. The review includes only studies using composite scales of
      acculturation. Studies were identified via electronic databases (i.e., PSYCHINFO,
      ETOH, and PUBMED) using search terms, and combinations thereof, including
      "acculturat*," "alcohol*," "Latino," and "Hispanic." This search was supplemented
      by recursive checking and author searches. Thirty-two articles were identified
      and coded on methodological characteristics; results from 24 disaggregating
      genders and using appropriate outcomes were summarized. RESULTS: Higher
      acculturation was very consistently associated with higher odds of drinking among
      women, even controlling for demographic covariates. The evidence for women also
      suggested associations between higher acculturation and heavier drinking on other
      outcomes, including total volume, drinking frequency, typical quantity,
      heavy/problem drinking, drinking problems, and abuse/dependence, despite some
      null results. Relationships were weaker and ambiguous among men. Some evidence
      suggested that highly acculturated men are (compared with peers low on
      acculturation) more prone to drink, and perhaps as a result, can show higher
      consumption and problems. However, results also implied that, among male
      drinkers, higher acculturation may be associated with a lighter drinking pattern.
      Important study limitations were identified, including low power, aggregation of
      nondrinkers with drinkers, restrictive sampling, measurement issues, and
      analytical issues. CONCLUSIONS: The pattern of results suggests important
      associations between acculturation and drinking outcomes-particularly for women
      but conclusions are tempered by serious methodological limitations. The review
      urges further research, particularly large-scale, longitudinal studies,
      addressing these limitations.

PMID- 18034693
TI  - A haplotype analysis of CYP2E1 polymorphisms in relation to alcoholic phenotypes
      in Mexican Americans.
AB  - BACKGROUND: Studies regarding the association between the 4 polymorphisms of
      CYP2E1 (CYP2E1*1D, *5B, *6, and *1B) and alcoholism are inconsistent and
      inconclusive. The purpose of the present study was to clarify previously
      discordant studies by haplotype analysis in the Mexican American population.
      METHODS: The 4 polymorphisms of CYP2E1 were studied in 334 alcoholics and 365
      controls. Genotype, allele, and haplotype frequency comparisons between
      alcoholics and controls were assessed. Patterns of linkage disequilibrium (LD) at
      CYP2E1 were determined. Reconstructed haplotypes were tested for associations
      with clinical phenotypes (age onset of drinking, Maxdrinks, and smoking status).
      RESULTS: No significant associations between the 4 polymorphisms of CYP2E1 and
      alcoholism were revealed by single allele tests. High LD was found between the
      CYP2E1 c2 and C alleles in Mexican Americans. Eleven haplotypes were present in
      the 699 participants. The 6 main haplotypes with frequencies higher than 1% made
      up 97% of the total halpotypes. The frequency of subjects carrying H6 (1C-c2-C
      A2) was significantly higher in alcoholics than in controls (p = 0.0001). In
      contrast, the frequencies of H7 (1C-c2-C-A1) and H10 (1C-c2-D-A1) were
      significantly lower in alcoholics than in controls (p = 0.0072 for H7 and p =
      0.0407 for H10). The frequency of H6 was significantly higher in alcoholics who
      had late onset of drinking than in nonalcoholic controls. Furthermore, the
      frequencies of H6 haplotype were also consistently higher in groups who had high
      number of maximum drinks (9 to 32 drinks) than in controls. When smokers are
      excluded, the frequencies of H6, H7, and H9 (1C-c2-D-A2) showed statistically
      significant differences between alcoholics and controls (p < 0.05). Moreover, the
      association between H6 and alcoholism become more robust when smokers are
      excluded. Furthermore, the frequency of H1 (1C-c1-D-A2) in alcoholic-smokers was
      much higher than in alcoholic-nonsmokers (p = 0.0028). In contrast, alcoholic
      smokers carried less H2 (1C-c1-D-A1) in comparison with alcoholic-nonsmokers (p =
      0.0417). The H3 (1D-c2-C-A2) frequency in alcoholic-smokers was much lower than
      in alcoholic-nonsmokers (p = 0.0042) and control-smokers (p = 0.0363).
      CONCLUSIONS: Our data demonstrate that carrying haplotype H6 might enhance
      susceptibility to developing alcoholism, but possessing the H7 or H10 haplotype
      appears to decrease this susceptibility. The H6, H7, and H9 haplotypes may play
      certain roles in different clinical phenotypes in Mexican American alcoholics. In
      addition, our data suggest that the H1, H2, and H3 haplotypes are associated with
      alcohol drinking and smoking. These results support that haplotype analysis is
      much more informative than single allele analysis. Our findings clearly indicate
      the importance of H6 haplotype in alcohol drinking in Mexican Americans.

PMID- 18034694
TI  - The effects of continuous and intermittent ethanol exposure in adolesence on the
      aversive properties of ethanol during adulthood.
AB  - BACKGROUND: Alcohol abuse among adolescents is prevalent. Epidemiological studies
      suggest that alcohol abuse during the adolescent developmental period may result
      in long-term changes such as an increased susceptibility to alcohol-related
      problems in adulthood. Laboratory findings suggest that alcohol exposure during
      the adolescent developmental period, as compared with adulthood, may
      differentially impact subsequent neurobehavioral responses to alcohol. The
      present study was designed to examine whether ethanol exposure, continuous versus
      intermittent, during the adolescent developmental period would alter the aversive
      properties of ethanol in adult C3H mice. METHODS: Periadolescent (PD28) male C3H
      mice were exposed to 64 hours of continuous or intermittent ethanol vapor. As a
      comparison, adult (PD70) C3H mice were also exposed to 64 hours of continuous or
      intermittent ethanol vapor. Six weeks after ethanol exposure, taste aversion
      conditioning was carried out on both ethanol pre-exposed and ethanol-naive
      animals using a 1-trial, 1-flavor taste-conditioning procedure. RESULTS: Ethanol
      exposure during the periadolescent period significantly attenuated a subsequent
      ethanol-induced conditioned taste aversion, as compared with control animals.
      Adult animals exposed to chronic ethanol vapor during adolescence showed less of
      an aversion to an ethanol-paired flavor than ethanol-naive adults. Intermittent
      exposure to ethanol vapor during periadolescence produced a greater attenuation.
      CONCLUSION: It is suggested that ethanol exposure during the periadolescent
      period results in long-term neurobehavioral changes, which lessen a conditioned
      aversion to ethanol in adulthood. It is suggested that this age-related effect
      may underlie the increased susceptibility to alcohol-related problems which is
      negatively correlated with the age of onset for alcohol abuse.

PMID- 18034696
TI  - Rates and correlates of relapse among individuals in remission from DSM-IV
      alcohol dependence: a 3-year follow-up.
AB  - BACKGROUND: There is little information on the stability of abstinent and
      nonabstinent remission from alcohol dependence in the general U.S. population.
      The aim of this study was to examine longitudinal changes in recovery status
      among individuals in remission from DSM-IV alcohol dependence, including rates
      and correlates of relapse, over a 3-year period. METHODS: This analysis is based
      on data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and
      Related Conditions (NESARC), a nationally representative sample of U.S. adults
      aged 18 years and older originally interviewed in 2001 to 2002 and reinterviewed
      in 2004 to 2005. The Wave 1 NESARC identified 2,109 individuals who met the DSM
      IV criteria for full remission from alcohol dependence. Of these, 1,772 were
      reinterviewed at Wave 2, comprising the analytic sample for this study. Recovery
      status at Wave 2 was examined as a function of type of remission at Wave 1, with
      a focus on rates of relapse, alternately defined as recurrence of any alcohol use
      disorder (AUD) symptoms and recurrence of DSM-IV alcohol dependence. Logistic
      regression models were used to estimate the odds of relapse among asymptomatic
      risk drinkers and low-risk drinkers relative to abstainers, adjusted for a wide
      range of potential confounders. RESULTS: By Wave 2, 51.0% of the Wave 1
      asymptomatic risk drinkers had experienced the recurrence of AUD symptoms,
      compared with 27.2% of low-risk drinkers and 7.3% of abstainers. Across all ages
      combined, the adjusted odds of recurrence of AUD symptoms relative to abstainers
      were 14.6 times as great for asymptomatic risk drinkers and 5.8 times as great
      for low-risk drinkers. The proportions of individuals who had experienced the
      recurrence of dependence were 10.2, 4.0, and 2.9%, respectively, and the adjusted
      odds ratios relative to abstainers were 7.0 for asymptomatic risk drinkers and
      3.0 for low-risk drinkers. Age significantly modified the association between
      type of remission and relapse. Differences by type of remission were not
      significant for younger alcoholics, who had the highest rates of relapse.
      CONCLUSIONS: Abstinence represents the most stable form of remission for most
      recovering alcoholics. Study findings highlight the need for better approaches to
      maintaining recovery among young adults in remission from alcohol dependence, who
      are at particularly high risk of relapse.

PMID- 18034695
TI  - fMRI BOLD response to the eyes task in offspring from multiplex alcohol
      dependence families.
AB  - BACKGROUND: Increased susceptibility for developing alcohol dependence (AD) may
      be related to structural and functional differences in brain circuits that
      influence social cognition and more specifically, theory of mind (ToM). Alcohol
      dependent individuals have a greater likelihood of having deficits in social
      skills and greater social alienation. These characteristics may be related to
      inherited differences in the neuroanatomical network that comprises the social
      brain. METHODS: Adolescent/young adult participants from multiplex AD families
      and controls (n = 16) were matched for gender, age, IQ, education, and handedness
      and administered the Eyes Task of Baron-Cohen during functional magnetic
      resonance imaging (fMRI). RESULTS: High-risk (HR) subjects showed significantly
      diminished blood oxygen level dependent (BOLD) response in comparison with low
      risk control young adults in the right middle temporal gyrus (RMTG) and the left
      inferior frontal gyrus (LIFG), areas that have previously been implicated in ToM
      tasks. CONCLUSIONS: Offspring from multiplex families for AD may manifest one
      aspect of their genetic susceptibility by having a diminished BOLD response in
      brain regions associated with performance of ToM tasks. These results suggest
      that those at risk for developing AD may have reduced ability to empathize with
      others' state of mind, possibly resulting in diminished social skill.

PMID- 18034697
TI  - The relationship between alcohol problems and dependence, conduct problems and
      diagnosis, and number of sex partners in a sample of young adults.
AB  - BACKGROUND: Heavy drinking is associated with an increased number of sexual
      partners. This study examined the extent to which alcohol dependence and conduct
      disorder are associated with the number of sexual partners and membership in a
      risk group of having a high number of sexual partners (10 or more). METHODS: Data
      were obtained by personal interview from 601 relatives (aged 18 to 25 years) of
      alcohol-dependent probands who participated in the Collaborative Study on the
      Genetics of Alcoholism (COGA) project. Analyses examined the independent
      contribution of problem drinking (defined as having at least one symptom of DSM
      IV alcohol dependence) and alcohol dependence, some conduct problems (defined as
      having at least one symptom of DSM-IV conduct disorder), conduct disorder, family
      status (defined as whether participant lived with both biological parents during
      childhood), educational attainment, gender, race, age at first intercourse, and
      age at time of interview to the number of sexual partners and to having 10 or
      more sexual partners. RESULTS: After controlling for other variables, alcohol
      dependence, problem drinking, race, age at first intercourse, and age at time of
      interview were significantly associated with number of sexual partners. The risk
      for having 10 or more sexual partners rose substantially for those who were
      alcohol dependent (OR = 2.5, 1.3-4.5, p = 0.004) and those with conduct disorder
      (OR = 1.8, 1.0-3.3, p = 0.041) after controlling for other variables. There is
      also a trend toward problem drinking and some conduct problems being associated
      with the risk of having 10 or more sexual partners though this did not reach
      statistical significance. CONCLUSIONS: These analyses demonstrate that alcohol
      dependent individuals and those with conduct disorder are at risk for increased
      number of sexual partners (10 or more). Sexually transmitted disease prevention
      efforts should target individuals with these two conditions to help decrease high
      risk sexual behaviors.

PMID- 18034698
TI  - Alcohol consumption before sleep is associated with severity of sleep-disordered
      breathing among professional Japanese truck drivers.
AB  - BACKGROUND: Alcohol consumption as well as overweight is known to aggravate the
      severity of sleep-disordered breathing (SDB), but little is known about alcohol
      consumption in truck drivers. The aim of this study was to examine the
      relationship between alcohol consumption and SDB among truck drivers. METHODS: We
      conducted a cross-sectional study of 1,465 men aged 20-69 years who were
      registered with the Japanese Trucking Association. The 3% oxygen desaturation
      index (3%ODI) was selected as an indicator of SDB, representing the number of
      desaturation events per hour of recording time in which blood oxygen fell by > or
      =3% based on overnight pulse-oximetry. Participants completed a self-administered
      questionnaire including alcohol consumption on the same night for SDB assessment.
      RESULTS: The prevalence of 3%ODI > or =5, > or =10, and > or =15/h was 25.4%,
      11.1%, and 6.6% respectively. The multivariable odds ratios (OR) of 3%ODI > or =
      10/h were 1.5(0.9-2.5) for 0.5 to <1.0 g of alcohol intake/kg and 3.4(1.8-6.6)
      for > or =1.0 g of alcohol intake/kg compared with non-drinkers. Similar
      associations with alcohol consumption were observed for 3%ODI > or =5 and > or
      =15/h. The relation between alcohol consumption (> or =1.0 g of alcohol
      intake/kg) and 3%ODI > or = 10/h tended to be more evident among men with body
      mass index (BMI) <23.4 kg/m(2) than those with BMI >or = 23.4 kg/m(2) [11.4 (3.2
      41) vs. 1.2 (0.6-2.7), p = 0.18 for interaction]. A similar trend was observed
      for 3%ODI > or= 5/h. CONCLUSIONS: The prevalence of undiagnosed SDB and the
      significant association of alcohol consumption with SDB severity emphasize the
      need for SDB screening and alcohol modification as well as weight control to
      prevent and control SDB among truck drivers.

PMID- 18034700
TI  - Acute ethanol potentiates the clock-speed enhancing effects of nicotine on timing
      and temporal memory.
AB  - BACKGROUND: Acute ethanol administration potentiates some of the behavioral
      effects of nicotine, although the extent of this effect is unknown. The present
      investigation assessed the ability of ethanol to potentiate nicotine's effect on
      the overestimation of multisecond durations as a result of an increase in the
      speed of an internal clock. METHODS: Adult male rats were exposed to the acute
      effects of ethanol (0.0, 0.5, 1.5, and 3.0 g/kg; IG) which was given 10 minutes
      prior to the administration of nicotine (0.0, 0.3, 0.6, and 1.0 mg/kg; IP). The
      effects of these combined treatments on timing and temporal memory were assessed
      using 18- and 36-second peak-interval procedures with separate visual/spatial
      cues for responding. RESULTS: When administered alone, ethanol had no consistent
      effect on peak time, but decreased peak rate, and increased peak spread as a
      function of dose. In contrast, nicotine alone shifted the peak times of the
      response distributions leftward in a proportional manner as a function of dose.
      When administered after pretreatment with ethanol, nicotine's effect on the
      horizontal placement of the peak functions was potentiated. CONCLUSIONS: The
      observation that ethanol pretreatment potentiates the clock-speed enhancing
      effects of subsequently administered nicotine is discussed in terms of the role
      of alpha7-nicotinic acetylcholine receptors and dopamine-glutamate interactions
      in cortico-striatal circuits thought to subserve interval timing.

PMID- 18034699
TI  - Ethanol alters production and secretion of estrogen-regulated growth factors that
      control prolactin-secreting tumors in the pituitary.
AB  - BACKGROUND: Chronic administration of ethanol increases plasma prolactin levels
      and enhances estradiol's mitogenic action on the lactotropes of the pituitary
      gland. The present study was conducted to determine whether ethanol's lactotropic
      cell-proliferating action, like estradiol's, is associated with alteration in the
      production of 3 peptides that regulate cell growth: transforming growth factor
      beta 1 (TGF-beta1), TGF-beta3 and basic fibroblast growth factor (bFGF). METHODS:
      Using ovariectomized Fischer-344 female rats, we determined ethanol's and
      estradiol's actions on lactotropic cell proliferation and growth-regulatory
      peptide production and release in the pituitary gland during tumorigenesis.
      RESULTS: Ethanol increased basal and estradiol-enhanced mitosis of lactotropes in
      the pituitary glands of ovariectomized rats. The level of growth-inhibitory TGF
      beta1 was reduced in the pituitary following ethanol and/or estradiol treatment
      for 2 and 4 weeks. In contrast, ethanol and estradiol alone as well as together
      increased levels of growth-stimulatory TGF-beta3 and bFGF in the pituitary at 2
      and 4 weeks. In primary cultures of pituitary cells, both ethanol and estradiol
      reduced TGF-beta1 release and increased TGF-beta3 and bFGF release at 24 hours.
      Ethanol's effect on growth factor levels in the pituitary or growth factor
      release from the pituitary cells was less than that of estradiol. When ethanol
      and estradiol were applied together, their individual effects on these growth
      factors were amplified. CONCLUSIONS: These results confirm estradiol's modulation
      of pituitary growth factor production and release, and provide evidence that
      ethanol, like estradiol, alters the production and secretion of growth-regulatory
      peptides controlling lactotropic cell proliferation.

PMID- 18034701
TI  - Formic acid, a novel metabolite of chronic ethanol abuse, causes neurotoxicity,
      which is prevented by folic acid.
AB  - BACKGROUND: Methanol is endogenously formed in the brain and is present as a
      congener in most alcoholic beverages. Because ethanol is preferentially
      metabolized over methanol (MeOH) by alcohol dehydrogenase, it is not surprising
      that MeOH accumulates in the alcohol-abusing population. This suggests that the
      alcohol-drinking population will have higher levels of MeOH's neurotoxic
      metabolite, formic acid (FA). FA elimination is mediated by folic acid.
      Neurotoxicity is a common result of chronic alcoholism. This study shows for the
      first time that FA, found in chronic alcoholics, is neurotoxic and this toxicity
      can be mitigated by folic acid administration. OBJECTIVE: To determine if FA
      levels are higher in the alcohol-drinking population and to assess its
      neurotoxicity in organotypic hippocampal rat brain slice cultures. METHODS: Serum
      and CSF FA was measured in samples from both ethanol abusing and control
      patients, who presented to a hospital emergency department. FA's neurotoxicity
      and its reversibility by folic acid were assessed using organotypic rat brain
      hippocampal slice cultures using clinically relevant concentrations. RESULTS:
      Serum FA levels in the alcoholics (mean +/- SE: 0.416 +/- 0.093 mmol/l, n = 23)
      were significantly higher than in controls (mean +/- SE: 0.154 +/- 0.009 mmol/l,
      n = 82) (p < 0.0002). FA was not detected in the controls' CSF (n = 20), whereas
      it was >0.15 mmol/l in CSF of 3 of the 4 alcoholic cases. Low doses of FA from 1
      to 5 mmol/l added for 24, 48 or 72 hours to the rat brain slice cultures caused
      neuronal death as measured by propidium iodide staining. When folic acid (1
      micromol/l) was added with the FA, neuronal death was prevented. CONCLUSIONS:
      Formic acid may be a significant factor in the neurotoxicity of ethanol abuse.
      This neurotoxicity can be mitigated by folic acid administration at a clinically
      relevant dose.

PMID- 18034702
TI  - Qualitative and nutritional differences in processing tomatoes grown under
      commercial organic and conventional production systems.
AB  - Organically grown products experienced a doubling in percent penetration of
      organic sales into retail markets during the period from 1997 to 2003; however,
      there is still a debate over the perceived quality advantage of organically grown
      fruits and vegetables. In a study focusing on commercial production of processing
      tomatoes, samples were analyzed from 4 growers with matched organic and
      conventional fields. For the 4 growers studied, individual analysis of variance
      results indicated that tomato juice prepared from organically produced tomatoes
      on some farms was significantly higher in soluble solids ( degrees Brix), higher
      in consistency, and titratable acidity, but lower in red color, ascorbic acid,
      and total phenolics content in the microwaved juice. Results were significantly
      different among specific growers, and this may be attributed to differences in
      soil type and soil nutrients, tomato cultivar, environmental conditions, or other
      production-related factors. Higher levels of soluble solids, titratable acidity,
      and consistency are desirable for the production of tomato paste, in that
      tomatoes with these attributes may be more flavorful and require less thermal
      treatment. This has the potential to result both in cost savings from less energy
      required in paste manufacture and potentially a higher quality product due to
      less thermal degradation of color, flavor, and nutrients. Future work may involve
      a larger number of commercial growers and correlation to controlled university
      research plots.

PMID- 18034703
TI  - Characterization of a thermostable and acidic-tolerable beta-glucanase from
      aerobic fungi Trichoderma koningii ZJU-T.
AB  - An extreme thermostable and acidic tolerable beta-glucanase was isolated and
      characterized from aerobic fungi Trichoderma koningii ZJU-T. The optimal reaction
      temperature and pH for the beta-glucanase were 100 degrees C and pH 2.0,
      respectively. The beta-glucanase showed increased stability at higher
      temperatures and lower pH values when compared to other beta-glucanases. The
      optimum conditions for the beta-glucanase stability were found to be pH 4.0 and
      80 degrees C. Even subjected to 100 degrees C for 3 h, beta-glucanase activity
      did not show significant reduction. Moreover, K(+) significantly enhanced beta
      glucanase activity at the concentration of 1 mM, while EDTA and other metal ions
      such as Mg(2+), Mn(2+), Zn(2+), Ca(2+), Fe(2+), Pb(2+), and Fe(3+) inhibited beta
      glucanase activity. Denaturants, including sodium dodecyl sulfate (SDS) and
      mercaptoethanol, also inhibited beta-glucanase activity at a concentration of 5%.
      However, in the presence of 7 M urea, residual activity of the beta-glucanase
      still remained 14.5%.

PMID- 18034704
TI  - Carotenoids and color of fruit juice and milk beverage mixtures.
AB  - Seventeen commercially available, "ready to drink" fortified beverages consisting
      of mixtures of fruit juices and milk were analyzed to evaluate their carotenoid
      profile (including their Z/E stereoisomers) and color during their commercial
      shelf life. Lightness (L*) was found to be correlated with the content of milk in
      the mixtures (r= 0.649) whereas red-yellow colors were correlated with the
      contents of alpha-carotene, beta-cryptoxanthin, and beta-carotene supplied by the
      fruit. The beverages stored under refrigeration (4 +/- 2 degrees C) showed higher
      luminosity (L*) and higher saturation of color (C*) and yellowness (b*).
      Differences (P < 0.05) in the levels of carotenoids were found among the
      beverages. Common fruits such as apple, lemon, pear, strawberry, kiwifruit,
      pineapple, and banana were low in carotenoids. However, orange, apricot, mango,
      and peach contributed significantly (P < 0.05) to increasing beta-cryptoxanthin
      and beta-carotene concentrations. Passion fruit supplied zeta-carotene, and the
      presence of carrot increased the levels of alpha-carotene and beta-carotene.
      Conversion of all-Ebeta-carotene and beta-cryptoxanthin to their Z isomers took
      place in 8 of the 17 samples containing alpha-carotene and in 9 of the 13 samples
      containing beta-cryptoxanthin, respectively, which resulted in some loss of
      provitamin A activity and nutritional value.

PMID- 18034705
TI  - Browning prevention by ascorbic acid and 4-hexylresorcinol: different mechanisms
      of action on polyphenol oxidase in the presence and in the absence of substrates.
AB  - We have investigated the mechanism of action of 4-hexylresorcinol (4-HR) and
      ascorbic acid (AA) on the polyphenol oxidase (PPO) catalyzed oxidation of
      phenolic substrates. Incubation of PPO with 4-HR diminishes strongly PPO
      activity. This effect can be erroneously interpreted, due to the high affinity of
      4-HR for PPO, as irreversible inactivation of PPO. However, PPO activity can be
      recovered by dialysis after incubation with 4-HR. 4-hexylresorcinol is a
      canonical enzyme inhibitor that binds preferentially to the oxy form of PPO. It
      is a mixed-type inhibitor, because it influences both apparent V(max) (1.26
      compared with 0.4 units in the absence and presence of 4-HR, respectively) and
      K(m) values (0.28 mM compared with 0.97 mM in the absence and in the presence of
      4-HR, respectively) of PPO. AA can prevent browning by 2 different mechanisms: In
      the absence of PPO substrates it inactivates PPO irreversibly, probably through
      binding to its active site, preferentially in its oxy form. In the presence of
      PPO substrates, AA reduces PPO oxidized reaction products, which results in a lag
      phase when measuring PPO activity by monitoring dark product formation but not
      when monitoring O(2) consumption. The simultaneous use of both 4-HR and AA on PPO
      results in additive prevention of browning.

PMID- 18034706
TI  - Chemical structure and physical properties of mung bean starches isolated from 5
      domestic cultivars.
AB  - Chemical structure and physical properties of starches isolated from 5 domestic
      mung bean cultivars (Gyungsun, Geumsung, Sunhwa, Eohul, and Jangan) were
      examined. The granules were jelly bean like in shape and smooth on surface, and
      the size was within 10 to 30 microm. Mung bean starches displayed a C(A)-type
      crystalline structure when judged by the X-ray diffraction patterns. Branch chain
      length distribution patterns of amylopectin (AP) revealed that peak chain length
      of APs was at either DP (degree of polymerization) 12 or DP13. Apparent amylose
      contents of 5 cultivars by iodine affinity test were 31.7% to 33.8%. Mung bean
      APs showed a unique molecular size distribution that has not been observed from
      other plant-derived starches. Two distinct peaks of AP fraction were identified
      on the size-exclusion chromatogram, and the ratios of these 2 peaks were
      different depending on the mung bean cultivars. Weight-average chain length
      (CL(avg)) of APs was in the range of 16.9 (Eohul) and 17.5 (Geumsung). The onset
      temperature (T(o)) and enthalpy change (DeltaH(gel)) of starch gelatinization
      were 54.6 to 60.2 degrees C and 11.6 to 13.2 J/g. The DeltaH of the retrograded
      mung bean starches was 5.5 to 6.6 J/g, which indicated 44.5% to 52.7% of
      recrystallization. The pasting temperature, peak viscosity, and setback were 66.1
      to 69.2 degrees C, 510 to 579 Rapid Visco Unit (RVU), and 66 to 90 RVU,
      respectively.

PMID- 18034707
TI  - Comparison of kinetic profile of free and immobilized glucose oxidase,
      immobilized on low-density polyethylene using UV polymerization.
AB  - Bioactive packaging is an important area of active packaging in which an active
      component is incorporated into the food contact surface of the package to
      interact with the food components without itself migrating into the food.
      Embedding bioactivity in a UV polymerizable resin is a novel and versatile
      technique for incorporating bioactive components into food packaging. In a
      previous article, glucose oxidase was immobilized in a packaging material using a
      UV curable resin. The relevance of this model system for deoxygenation of fruit
      juices was discussed. Though the technique efficiently immobilized enzymes in
      packaging material, during polymerization and immobilization the catalytic
      ability of the enzyme was not specifically explored. This article compares and
      contrasts the catalytic ability in terms of the kinetic profile of free and
      immobilized enzyme for the same model system: deoxygenation of juices. Kinetic
      behavior of immobilized and free glucose oxidase enzyme was evaluated at both
      shelf stable (room temperature) and refrigerated storage conditions to simulate
      the actual package life. It was observed that both the free enzyme and the
      immobilized enzymes follow the Michaelis-Menten kinetics model. There was no
      significant difference between the catalytic ability (k(cat)/K(m)) of free and
      immobilized enzymes at treatment temperatures (30, 25, and 10 degrees C);
      however, at refrigeration temperature (5 degrees C), the values for free enzyme
      were significantly higher than the immobilized enzyme.

PMID- 18034708
TI  - The effect of natural cheddar cheese ripening on the functional and textural
      properties of the processed cheese manufactured therefrom.
AB  - Cheddar cheese ripened at 8 degrees C was sampled at 7, 14, 28, 56, 112, and 168
      d and subsequently used for the manufacture of processed cheese. The cheddar
      cheese samples were analyzed throughout ripening for proteolysis while the
      textural and rheological properties of the processed cheeses (PCs) were studied.
      The rate of proteolysis was the greatest in the first 28 d of cheddar cheese
      ripening but began to slow down as ripening progressed from 28 to 168 d. A
      similar trend was observed in changes to the texture of the PC samples, with the
      greatest decrease in hardness and increase in flowability being in the first 28 d
      of ripening. Confocal scanning laser microscopy showed that the degree of
      emulsification in the PC samples increased as the maturity of the cheddar cheese
      ingredient increased from 7 to 168 d. This increased emulsification resulted in a
      reduction in the rate of softening in the PC in samples manufactured from cheddar
      cheese bases at later ripening times. Multivariate data analysis was performed to
      summarize the relationships between proteolysis in the cheddar cheese bases and
      textural properties of the PC made therefrom. The proportion of alpha(s)(1)
      casein (CN) in the cheddar cheese base was strongly correlated with hardness,
      adhesiveness, fracturability, springiness, and storage modulus values for the
      corresponding PC. Degradation of alpha(s) (1)-CN was the proteolytic event with
      the strongest correlation to the softening of PC samples, particularly those
      manufactured from cheddar cheese in the first 28 d of ripening.

PMID- 18034709
TI  - Determination of processing effects and of storage stability on vitamin K1
      (Phylloquinone) in Sea Buckthorn Berries (Hippophae rhamnoides L. ssp.
      rhamnoides) and related products.
AB  - Phylloquinone (vitamin K(1)) is the primary dietary source of vitamin K.
      Processing effects and stability of phylloquinone were investigated during juice
      and concentrate production from sea buckthorn (Hippophae rhamnoides) using
      berries from 2 different growing areas. During industrial juice production the
      technological processing of the berries caused a loss of about 36% to 54%
      phylloquinone in the generated juice. The following processing steps leading to
      the concentrated juice resulted in a complete depletion of phylloquinone. Sea
      buckthorn berries and juice were stored at 6, 25, and 40 degrees C for up to 7 d
      to determine the temperature effects on phylloquinone during storage. Content of
      vitamin K(1) in sea buckthorn berries was affected by storage time and storage
      temperature. Storage of freshly harvested berries resulted in a significant
      increase (P < 0.01) of phylloquinone ranging from 21% up to 186% (wet weight).
      The juices showed almost identical significant degradation (P < 0.01) of
      phylloquinone of about 18% to 32% at 6, 25, and 40 degrees C indicating that
      intensity of decomposition is independent of temperature (6 to 40 degrees C) and
      storage time in the range of consumer storage conditions.

PMID- 18034710
TI  - Characterization of edible film fabricated with channel catfish (Ictalurus
      punctatus) gelatin extract using selected pretreatment methods.
AB  - Farm-raised catfish are important to the economy of the southeastern states in
      the United States, and catfish processing produces about 55% of by-products for
      inexpensive sale. Therefore, the utilization of catfish by-products is of great
      interest to the catfish industry. The objectives of this research were to
      determine the optimum pretreatment method to extract catfish gelatin for edible
      film application, and to characterize physical, mechanical, and barrier
      properties of edible films fabricated with catfish skin gelatin. Catfish skins
      obtained from a local plant were treated with 6 selected pretreatment methods.
      The main extraction was performed with deionized water at 50 degrees C after
      pretreatment. The gelatin yield was calculated and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) was performed to characterize
      molecular weight (MW) profile. Color, tensile strength (TS), elongation, and
      water barrier property were determined to characterize the fabricated catfish
      gelatin films. From the results of gelatin yield, color, SDS-PAGE, as well as
      mechanical and barrier properties of the film, the pretreatment method with 0.25
      M NaOH and 0.09 M acetic acid, followed by extraction at 50 degrees C for 3 h,
      was determined as the optimum extraction method. The catfish gelatin exhibited
      higher MW fractions than commercial mammalian gelatin. The catfish gelatin
      extracts possessed film-forming properties determined by TS, elongation, and
      water vapor permeability (WVP) comparable to those of commercial mammalian
      gelatin. The selected formula for catfish gelatin film was determined as 1%
      gelatin and 20% glycerol, resulting in greatest TS and lowest WVP.

PMID- 18034711
TI  - Oregano and rosemary extracts inhibit oxidation of long-chain n-3 fatty acids in
      menhaden oil.
AB  - Capabilities of methanol extracts from oregano and rosemary in retarding
      oxidation of long-chain polyunsaturated fatty acids, docosahexaenoic acid C22:6
      (DHA) and eicosapentaenoic acid C20:5 (EPA), in menhaden oil were investigated.
      The fish oils after mixing with the extracts at different concentrations were
      oxidized in an accelerated study by heating at 150 degrees C for 30 min or
      incubating at 60 degrees C for 5 d. After heating at 150 degrees C, only 15.9% of
      DHA and 18.5% of EPA remained in the fish oil without extract, while 38.8% to
      65.9% of DHA and 44.7% to 69.0% of EPA were retained in the fish oil mixed with
      1% to 5% of oregano extract. The highest retained DHA (56.9%) and EPA (58.0%) in
      the fish oils mixed with rosemary extract were observed at 2.5% addition.
      Increasing rosemary extract to 5% lowered its capability of inhibiting DHA and
      EPA oxidation. After incubation at 60 degrees C for 5 d, the highest inhibition
      capability was also found at 2.5% of added rosemary extract, and the oil retained
      88.2% DHA and 88.3% EPA. However, only 18.8% DHA and 23.6% EPA were retained in
      the fish oil mixed with 5% of oregano extract and no DHA and EPA were detected in
      the fish oil without extract after 5-d incubation at 60 degrees C. Thus,
      antioxidant activity of the rosemary extract was greater than that of oregano
      extract, but was sensitive to heat. The rosemary extract also demonstrated higher
      DPPH (2,2'-diphenyl-1-picrylhydrazyl) free radical scavenging capability, which
      was approximately 3 times higher than oregano extract, although there was no
      significant difference in the total phenolic contents between both extracts.

PMID- 18034712
TI  - Effect of high pressure treatment on the quality of rainbow trout (Oncorhynchus
      mykiss) and mahi mahi (Coryphaena hippurus).
AB  - High pressure processing (HPP) is becoming a promising seafood preservation
      method. The objective was to investigate the effect of HPP on quality of rainbow
      trout and mahi mahi during cold storage. Skinless fillets treated with different
      pressures (150, 300, 450, and 600 MPa for 15 min) and stored at 4 degrees C were
      analyzed at 1, 3, and 6 d storage. Red muscle was analyzed for lipid oxidation
      products by measuring thiobarbituric reactive substances (TBARS) and whole muscle
      was analyzed for total aerobic count, texture profile analysis, and color. A
      pressure of 300 MPa effectively inactivated the initial microbial population in
      rainbow trout (6-log reduction). However, inactivation of the initial population
      on mahi mahi was only about 4-log reduction at the same pressure. Microbial
      growth was significantly retarded after HPP. Color results showed that redness
      (a* value) of rainbow trout at 300 MPa and above was significantly (P < 0.05)
      lower compared to mahi mahi. TBARS values for rainbow trout increased with
      increased pressure, whereas the same trend was not seen for mahi mahi where
      maximum oxidation was found at 300 MPa and then declined. This study demonstrates
      the usefulness of HPP in seafood processing and the influence of species
      variation on processing parameters. The optimum HPP conditions for influencing
      lipid oxidation, microbial load, and color changes were found to be 300 MPa for
      rainbow trout and 450 MPa for mahi mahi.

PMID- 18034713
TI  - Cellulase-assisted extraction of oligosaccharides from defatted rice bran.
AB  - Defatted rice bran was subjected to cellulase treatment in order to increase its
      extractable oligosaccharides. Various combinations of enzyme concentration (0%,
      0.5%, 1.0%, and 2.0%), temperature (room, 30, 40, and 50 degrees C), and time (1,
      3, 5, and 16 h) were tested to identify the optimum extraction conditions. The
      saccharide content and composition of the extracts were analyzed by high
      performance anion-exchange chromatography with pulsed amperometric detection
      (HPAEC-PAD). Digestibility was assayed in vitro with human salivary and porcine
      pancreatic alpha-amylases. Extraction yield ranged from 13.4% (without cellulase)
      to 39.9% (with 2% cellulase). Total carbohydrates, reducing sugars, and crude
      protein of the dried extracts ranged from 69.2% to 87.2%, 18.7% to 62.3%, and
      7.1% to 22.3%, respectively. Mono- and disaccharides constituted more than 50% of
      the total carbohydrates in the extracts. Inherent oligosaccharides and those
      produced by cellulolysis made up less than 25%. The in vitro digestibility of the
      extracts by alpha-amylases was lower compared with that of the original rice bran
      sample and potato dextrin, which could be attributed to the increased
      concentrations of oligosaccharides and reducing sugars.

PMID- 18034714
TI  - Simultaneous depolymerization and decolorization of chitosan by ozone treatment.
AB  - Currently, depolymerization and decolorization of chitosan are achieved by
      chemical or enzymatic methods, which are time consuming and expensive. Ozone has
      been shown to be able to degrade macromolecules and remove pigments due to its
      high oxidation potential. In this study, the effects of ozone treatment on
      depolymerization and decolorization of chitosan were investigated. Crawfish
      chitosan was ozonated in water and acetic acid solution for 0, 5, 10, 15, and 20
      min at room temperature with 12 wt% gas. In this study, the effects of ozone
      treatment on depolymerization and decolorization of chitosan were investigated by
      measuring the molecular weight, viscosity, and color of chitosan. The color of
      ozone-treated chitosan was analyzed using a Minolta spectrophotometer. The degree
      of deacetylation was determined by a colloid titration method. Molecular weight
      of ozone-treated chitosan in acetic acid solution decreased appreciably as the
      ozone treatment duration increased. Ozonation for 20 min reduced the molecular
      weight of the chitosan by 92% (104 kDa) compared to the untreated chitosan (1333
      kDa) with a decrease in viscosity of the chitosan solution. Ozonation for 5 min
      markedly increased the whiteness of chitosan with a molecular weight of 432 kDa;
      however, further ozonation resulted in development of yellowness. In the case of
      the ozonation in water, there were no significant differences in the molecular
      weight and color between ozone-treated chitosans. This study showed that ozone
      can be used to modify molecular weight and remove pigments of chitosan without
      chemical use in a shorter time and with less cost.

PMID- 18034715
TI  - Amino acid, fatty acid, and mineral profiles of materials recovered from rainbow
      trout (Oncorhynchus mykiss) processing by-products using isoelectric
      solubilization/precipitation.
AB  - Protein, lipid, and insolubles (bones, skin, scales, fins, insoluble protein, and
      more) were recovered from rainbow trout processing by-products by means of
      isoelectric solubilization/precipitation at basic pH and acidic pH. Isoelectric
      solubilization/precipitation of the trout processing by-products resulted in the
      recovery of protein that was higher (P < 0.05) in essential amino acids (EAAs),
      non-EAAs, and total EAA/total AA ratio when compared to the processing by
      products. Basic pH treatments yielded a higher (P < 0.05) content of EAAs than
      the acidic pH treatments. Nutritional quality of the recovered protein was high
      based on EAAs meeting the FAO/WHO/UNU recommendations for adults. The presence of
      omega-3 and omega-6 fatty acids (omega-3, omega-6 FAs) and the omega-3/omega-6
      ratio in the recovered lipids were similar to the trout processing by-products,
      indicating that the pH treatments had no effect on these FAs. Ca and P contents
      of the processing by-products exceeded the recommended dietary allowances (RDA),
      but Fe and Mg did not. Basic pH treatments yielded protein with the lowest (P <
      0.05) amount of minerals and the highest (P < 0.05) amount of Ca, P, and Mg in
      the insolubles when compared to acidic pH. The isoelectric
      solubilization/precipitation of the processing by-products effectively removed
      minerals from the recovered protein without removal of the bones, skin, scales,
      fins, and so on, prior to processing. The results indicated that isoelectric
      solubilization/precipitation, particularly at basic pH, permitted recovery of
      high-quality protein and lipids from fish processing by-products for human food
      uses; also, the recovered insolubles may be used in animal feeds as a source of
      minerals.

PMID- 18034716
TI  - Extrusion of pea starch containing lysozyme and determination of antimicrobial
      activity.
AB  - Pea starch, which has inherently good gel strength, was used as the source
      material for manufacturing a biodegradable and bioactive packaging material.
      Extrudates containing 99% pea starch and 1% lysozyme were produced under various
      extrusion conditions (high and low shear screw configurations, 30% to 40%
      moisture contents, 70 to 150 degrees C die temperatures). The physical and
      mechanical properties of the extrudates were determined through various expansion
      indices, piece and cell wall solid density, compression, and 3-point bending
      tests. The expansion of extrudates increased with an increase in die temperature,
      whereas increasing moisture content had the opposite effect. Extrudate densities
      decreased as extrusion temperature increased, whereas lower moisture content in
      the extrudate dough decreased extrudate densities. The elastic modulus and
      fracture strengths were highly correlated in a power-law fashion to relative
      density, showing that the mechanical properties of extrudates were dependent on
      solid density and foam structure. Up to 48% of the initial lysozyme activity was
      recovered from the extruded pea starch matrix. The lysozyme released from
      extrudates showed an inhibition zone against Brochotrix thermosphacta B2.
      Extruded pea starch matrix containing lysozyme has potential application as an
      edible and biodegradable packaging material with antimicrobial activity.

PMID- 18034717
TI  - Adhesion modeling on rough low linear density polyethylene.
AB  - Food adhesion is an important attribute that could have both positive and
      negative ramifications depending on the application. Yet, its quantification
      remains cumbersome and as a consequence adhesion models are scarce. The effect of
      surface roughness, free energy, and ozone treatment on adhesion of rough low
      linear density polyethylene films was investigated. Adhesion was measured by a
      180 degrees peel strength test. The plastic films were roughened (surface
      roughness ratio, r, ranged from 1.00 to 1.15). Exposing the film to ozone
      treatment (0 to 300 s) modified its surface free energy, gamma(s) (32.4 to 37.9
      mJ/m(2), respectively), and its polar component of the surface free energy,
      gamma(p)(s) (3.0 to 8.3 mJ/m(2), respectively). The films were coated with
      polyurethane capable of forming hydrogen bonds. Adhesion was found to be a
      function of the apparent contact angle of water, theta(ap[water]), surface
      roughness ratio, and surface free energy. The linear relationship between the
      apparent contact angle of water, theta(ap[water]), and gamma(p)(s) was
      incorporated in building an empirical model that quantifies peel strength as
      function of r and gamma(p)(s). The model showed good agreement with experimental
      data, especially for longer ozone exposures and rougher surfaces. The empirical
      model provides insight into the relationships between surface roughness, surface
      energy, and adhesion. Quantifying these effects could facilitate reducing biofilm
      forming on food equipment, antisticking treatments, or easy peel packages, or
      reducing food residues adhering to the food packages and consequently minimize
      oxidation, off flavors, and waste.

PMID- 18034718
TI  - Exploring imperfect squeezing flow measurements in a Teflon geometry for
      semisolid foods.
AB  - The method of imperfect lubricated squeezing flow in a Teflontrade mark geometry
      has been explored for the characterization of elongational behavior of custard
      and mayonnaise. Two Newtonian products, one of low (0.07 Pas) and one of high (18
      Pas) shear viscosity, were used as references. Measurements of custards and
      mayonnaises did not behave according to either the theory of lubricated or
      nonlubricated squeezing flow, as there were effects of the initial sample height
      and compression speed. Also, calculated values for the flow index were not as we
      had expected. The same was true for the Newtonian samples. An important factor
      explaining the effect of compression speed was the presence of a certain amount
      of friction, rendering both lubricated theory and nonlubricated theory
      nonapplicable. Correcting for (pseudo-) thixotropic behavior of custard and
      mayonnaise appears to be an effective way of obtaining realistic values for the
      flow index. The presence of buoyancy also affected the results, especially in the
      case of low viscous products and the effect of initial sample height. Other
      factors that played a role in the results were yield stress for custard and
      mayonnaise and instrumental artifacts associated with the imperfect setup of the
      measurement, especially for the highly viscous products. Quantitatively
      correcting the results for all of these factors is not possible at this point.
      Although the imperfect squeezing flow technique in a Teflon geometry is a very
      practical way to measure semisolids such as custard and mayonnaise under (partly)
      elongational deformation, the results should be regarded as more qualitative than
      quantitative.

PMID- 18034719
TI  - Electrical conductivity and physical properties of surimi-potato starch under
      ohmic heating.
AB  - Electrical conductivities of Alaska pollock surimi mixed with native and
      pregelled potato starch at different concentrations (0%, 3%, and 9%) were
      measured at different moisture contents (75% and 81%) using a multifrequency
      ohmic heating system. Surimi-starch paste was tested up to 80 degrees C at
      frequencies from 55 Hz to 20 KHz and at alternating currents of 4.3 and 15.5 V/cm
      voltage gradient. Electrical conductivity increased when moisture content,
      applied frequency, and applied voltage increased, but decreased when starch
      concentration increased. Electrical conductivity was correlated linearly with
      temperature (R(2) approximately 0.99). Electrical conductivity pattern
      (magnitude) changed when temperature increased, which was clearly seen after 55
      degrees C in the native potato starch system, especially at high concentration.
      This confirms that starch gelatinization that occurred during heating affects the
      electrical conductivity. Whiteness and texture properties decreased with an
      increase of starch concentration and a decrease of moisture content.

PMID- 18034720
TI  - Heat transfer models for predicting Salmonella enteritidis in shell eggs through
      supply chain distribution.
AB  - Egg and egg preparations are important vehicles for Salmonella enteritidis
      infections. The influence of time-temperature becomes important when the presence
      of this organism is found in commercial shell eggs. A computer-aided mathematical
      model was validated to estimate surface and interior temperature of shell eggs
      under variable ambient and refrigerated storage temperature. A risk assessment of
      S. enteritidis based on the use of this model, coupled with S. enteritidis
      kinetics, has already been reported in a companion paper published earlier in
      JFS. The model considered the actual geometry and composition of shell eggs and
      was solved by numerical techniques (finite differences and finite elements).
      Parameters of interest such as local (h) and global (U) heat transfer
      coefficient, thermal conductivity, and apparent volumetric specific heat were
      estimated by an inverse procedure from experimental temperature measurement. In
      order to assess the error in predicting microbial population growth, theoretical
      and experimental temperatures were applied to a S. enteritidis growth model taken
      from the literature. Errors between values of microbial population growth
      calculated from model predicted compared with experimentally measured
      temperatures were satisfactorily low: 1.1% and 0.8% for the finite difference and
      finite element model, respectively.

PMID- 18034721
TI  - Improvement of stability of oil-in-water emulsions containing caseinate-coated
      droplets by addition of sodium alginate.
AB  - The potential of sodium alginate for improving the stability of emulsions
      containing caseinate-coated droplets was investigated. One wt% corn oil-in-water
      emulsions containing anionic caseinate-coated droplets (0.15 wt% sodium
      caseinate) and anionic sodium alginate (0 to 1 wt%) were prepared at pH 7. The pH
      of these emulsions was then adjusted to 3.5, so that the anionic alginate
      molecules adsorbed to the cationic caseinate-coated droplets. Extensive droplet
      aggregation occurred when there was insufficient alginate to completely saturate
      the droplet surfaces due to bridging flocculation, and when the nonadsorbed
      alginate concentration was high enough to induce depletion flocculation.
      Emulsions with relatively small particle sizes could be formed over a range of
      alginate concentrations (0.1 to 0.4 wt%). The influence of pHs (3 to 7) and
      sodium chloride (0 to 500 mM) on the properties of primary (0 wt% alginate) and
      secondary (0.15 wt% alginate) emulsions was studied. Alginate adsorbed to the
      droplet surfaces at pHs 3, 4, and 5, but not at pHs 6 and 7, due to electrostatic
      attraction between anionic groups on the alginate and cationic groups on the
      adsorbed caseinate. Secondary emulsions had better stability than primary
      emulsions at pH values near caseinate's isoelectric point (pHs 4 and 5). In
      addition, secondary emulsions were stable up to higher ionic strengths (< 300 mM)
      than primary emulsions (<50 mM). The controlled electrostatic deposition method
      utilized in this study could be used to extend the range of application of dairy
      protein emulsifiers in the food industry.

PMID- 18034722
TI  - Exsanguination of turbot and the effect on fillet quality measured mechanically,
      by sensory evaluation, and with computer vision.
AB  - In order to investigate the impact of blood residues on the end quality of
      exsanguinated and unbled farmed turbot (Scophthalmus maximus), meat quality was
      evaluated using mechanical, sensory, and computer imaging techniques. The results
      show that exsanguination is important for improving the visual appearance, and
      the blood residue could be quantified using a computer imaging system. After 6 d
      of storage, mechanical analysis using puncture test or shear force showed no
      difference between exsanguinated and unbled fish. The trained taste panel was
      unable to detect any differences between exsanguinated and unbled fish after 6
      and 14 d of storage. We conclude that over a 2-wk period the blood residue in
      turbot meat does not affect texture or sensory quality, but does affect the
      visual appearance.

PMID- 18034723
TI  - Study on lycopene and antioxidant contents variations in tomatoes under air
      drying process.
AB  - Effects of factors such as tomato cultivars, drying temperatures (40, 80, and 120
      degrees C), and drying time (0 to 240 min) on tomato lycopene and the major
      antioxidant contents (MACs, herein as the sum of total phenolics and total
      flavonoids) during an air-drying process were investigated. The results showed
      that lycopene contents increased under all the drying temperatures during the
      first 60 min. However, the red tomato cultivars, that is, HR, SN, and TTL,
      exhibited a significant decrease in lycopene contents under 120 degrees C after
      drying for 75 min. According to the experimental data, an MAC threshold value of
      500 mg/100 g dry matter of tomato is proposed. When the MAC is lower than this
      value during air-drying, lycopene contents in all tomato cultivars would drop
      rapidly. In addition, the tomatoes in yellow color group, containing more MACs
      initially and retaining more MACs under air-drying at 40 to 80 degrees C, are
      proposed to be the proper tomato cultivars for thermal processing.

PMID- 18034724
TI  - Impact of particle size distribution on rheological and textural properties of
      chocolate models with reduced fat content.
AB  - With an increasing consumption of lipids nowadays, decreasing the fat content in
      food products has become a trend. Chocolate is a fat-based suspension that
      contains about 30%wt fat. Reducing fat content causes an increase in the molten
      chocolate viscosity. This leads to 2 major issues: difficulties in the process
      and a loss of eating quality in the final product, reported to have poor in-mouth
      melting properties, remain hard, and difficult to swallow. Literature shows that
      optimizing the particle size distribution (PSD), that is, having one with an
      increased packing fraction, can decrease the viscosity of highly concentrated
      suspensions. This study focuses on the impact of the PSD and fat content on the
      rheological properties, melting behavior, and hardness of chocolate models
      (dispersions of sugar in fat). We show that optimizing the PSD while reducing the
      fat content to a critical amount (22%wt) can decrease the viscosity of the molten
      material and reduce the hardness of the crystallized chocolate models. Melting in
      the mouth, characterized by an in vitro collapse speed, is faster for the samples
      with an optimized PSD. The decrease in the viscosity by optimizing the PSD in
      systems with a constant fraction of medium phase is based on the decrease of
      interparticle contact, reducing the particle aggregates strength, and structure
      buildup during flow or meltdown. In its crystallized state, the particle network
      is less interconnected, providing less resistance to breakage and meltdown.

PMID- 18034725
TI  - Effects of process parameters on quality changes of shrimp during drying in a jet
      spouted bed dryer.
AB  - The objective of the present study was to investigate the effects of various
      parameters, that is, concentration of salt solution (2%, 3%, 4%[w/v]), boiling
      time (3, 5, 7 min), drying air temperature (80, 100, 120 degrees C), and size of
      shrimp, on the kinetics of drying and various quality attributes of shrimp,
      namely, shrinkage, rehydration ability, texture, colors, and microstructure,
      during drying in a jet-spouted bed dryer. In addition, the effects of these
      processing parameters on the sensory attributes of dried shrimp were also
      investigated. Small shrimp (350 to 360 shrimp/kg) and large shrimp (150 to 160
      shrimp/kg) were boiled and then dried until their moisture content was around 25%
      (d.b.). It was found that the degree of color changes, toughness, and shrinkage
      of shrimp increased while the rehydration ability decreased with an increase in
      the concentration of salt solution and boiling time. Size of shrimp and drying
      temperature significantly affected all quality attributes of dried shrimp. The
      conditions that gave the highest hedonic scores of sensory evaluation for small
      dried shrimp are the concentration of salt solution of 2% (w/v), boiling time of
      7 min, and drying air temperature of 120 degrees C. On the other hand, the
      conditions that gave the highest hedonic scores of sensory evaluation for large
      dried shrimp are the concentration of salt solution of 4% (w/v), boiling time of
      7 min, and drying air temperature of 100 degrees C. The quality attributes of
      dried shrimp measured by instruments correlated well with the sensory attributes,
      especially the color of dried shrimp.

PMID- 18034726
TI  - Antibacterial activity directed isolation of compounds from Punica granatum.
AB  - Chemical investigation of the methanolic extract of pomegranate fruit following
      antibacterial activity directed isolation led to the isolation of pelargonidin-3
      galactose, cyanidin-3-glucose, gallic acid, quercetin, and myricetin. All these
      compounds exhibited substantial activity against species of corynebacteria,
      staphylococci, streptococci, Bacillus subtilis, Shigella, Salmonella, Vibrio
      cholera, and Escherichia coli. However, all these compounds were more active
      against Gram-positive species. On comparing the activity of all the isolated pure
      compounds, it was found that gallic acid showed the highest antibacterial
      activity against all the tested sensitive strains and the activity of the
      remaining pure compounds was almost same due to the structural similarities of
      the compounds. The reason for antibacterial activity of all pure compounds was
      attributed to their phenolic structure.

PMID- 18034727
TI  - Comparison of 3M Petrifilm environmental Listeria plates against standard
      enrichment methods for the detection of Listeria monocytogenes of epidemiological
      significance from environmental surfaces.
AB  - Environmental monitoring using sensitive methods for detection and elimination of
      harborage sites of Listeria monocytogenes is key to the control of this organism.
      The 3M Petrifilm Environmental Listeria (EL) Plate-a no enrichment method-was
      compared with the USDA/FSIS, modified USDA/FSIS (mUSDA), and ISO methods for
      detection/recovery of L. monocytogenes on 4 environmental surfaces (brick, dairy
      board, stainless steel, and epoxy resin). The efficacy of 3 sampling devices
      including the Microbial-Vac system((R)), environmental sponge, and 3M Quick swab
      in recovering epidemiologically significant strains of uninjured and sublethally
      injured L. monocytogenes from environmental surfaces was evaluated. Environmental
      surfaces were inoculated with Listeria to obtain final cell densities of
      approximately 10 to 100 CFU/100 cm(2). The surfaces were then sampled and
      processed. For all methods, percent recovery (% samples where Listeria was
      detected) was significantly higher (P < 0.05) for uninjured cells (75% to 100%)
      compared to injured cells (58.9% to 81.1%). The Petrifilm EL Plate method
      efficiently recovered both low level and injured Listeria populations from
      environmental test surfaces when used in conjunction with environmental sponge
      and the 3M Quick swab sampling. The mUSDA method was superior to all other
      methods for recovering both uninjured (100% recovery) and injured L.
      monocytogenes (80.8% to 81.1% recovery). Sponges and swabs were equally effective
      in recovering uninjured and injured Listeria and were significantly different (P
      < 0.05) from the Microbial-Vac system. The findings indicate that both mUSDA and
      Petrifilm EL Plate methods can be used for the detection of potentially injured
      Listeria on food processing environmental surfaces.

PMID- 18034728
TI  - Antimicrobial chitosan-lysozyme (CL) films and coatings for enhancing microbial
      safety of mozzarella cheese.
AB  - This study investigated the antimicrobial activities of chitosan-lysozyme (CL)
      composite films and coatings against tested microorganisms inoculated onto the
      surface of Mozzarella cheese. CL film-forming solutions (FFS) with a pH of 4.4 to
      4.5 were prepared by incorporating 0% or 60% lysozyme (per dry weight of
      chitosan) into chitosan FFS with or without a pH adjustment to 5.2. Sliced cheese
      was subjected to 3 CL package applications: film, lamination on a multilayer
      coextruded film, and coating. Cheese was inoculated with Listeria monocytogenes,
      Escherichia coli, or Pseudomonas fluorescens at 10(4) CFU/g, or with mold and
      yeast at 10(2) CFU/g. Inoculated cheese was individually vacuum packaged and
      stored at 10 degrees C for sampling at 1, 7, and 14 d for bacteria, and at 10,
      20, and 30 d for fungi. Inoculated bacteria survived but failed to multiply in
      untreated cheese during storage. Treated cheese received 0.43- to 1.25-, 0.40- to
      1.40-, and 0.32- to 1.35-log reductions in E. coli, P. fluorescens, and L.
      monocytogenes, respectively. Incorporation of 60% lysozyme in chitosan FFS showed
      greater antimicrobial effect than chitosan alone on P. fluorescens and L.
      monocytogenes. The pH adjustment only affected the antimicrobial activity on L.
      monocytogenes, with lower pH (unadjusted) showing greater antimicrobial effect
      than pH 5.2. Mold and yeast increased to 10(5) CFU/g in untreated cheese after 30
      d storage. Growth of mold was completely inhibited in cheese packaged with CL
      films, while 0.24- to 1.90- and 0.06- to 0.50-log reductions in mold populations
      were observed in cheese packaged with CL-laminated films and coatings,
      respectively. All CL packaging applications resulted in 0.01- to 0.64-log
      reduction in yeast populations.

PMID- 18034729
TI  - Identification of poultry meat-derived fatty acids functioning as quorum sensing
      signal inhibitors to autoinducer-2 (AI-2).
AB  - Autoinducer-2 (AI-2) is a compound that plays a key role in bacterial cell-to
      cell communication (quorum sensing). Previous research has shown certain food
      matrices inhibit this signaling compound. Using the reporter strain, Vibrio
      harveyi BB170, quorum-sensing inhibitors contained in poultry meat wash (PMW)
      samples were characterized by molecular weight and hydrophobic properties using
      liquid chromatography systems. Most fractions that demonstrated AI-2 inhibition
      were 13.7 kDa or less, and had hydrophobic properties. Hexane was used to extract
      inhibitory compounds from a PMW preparation and the extract was further separated
      by gas chromatography (GC). Several fatty acids were identified and quantified.
      Linoleic acid, oleic acid, palmitic acid, and stearic acid were each tested for
      inhibition at 0.1, 1, and 10 mM concentrations. All samples expressed AI-2
      inhibition (ranging from approximately 25% to 99%). Fatty acids, combined in
      concentrations equivalent to those determined by GC analysis, expressed
      inhibition at 59.5%, but higher combined concentrations (10- and 100-fold) had
      inhibition at 84.4% and 69.5%, respectively. The combined fatty acids (100-fold)
      did not demonstrate a substantial decrease in colony plate counts, despite
      presenting high AI-2 inhibition. These fatty acids, through modulating quorum
      sensing by inhibition, may offer a unique means to control foodborne pathogens
      and reduce microbial spoilage.

PMID- 18034730
TI  - Lytic antimicrobial activity of hen egg white lysozyme immobilized to polystyrene
      beads.
AB  - Lysozyme [EC 3.2.1.17] was covalently attached to polystyrene resin beads by the
      sole histidine residue (His-15) through peptide spacers of various lengths. The
      spacers were amino acid chains composed of 6-aminocaproic acid synthesized with
      the solid phase peptide synthesis method. Immobilized lysozyme with a spacer
      length of three 6-aminocaproic acid units (2736 U/g resin with a protein load of
      2.21 mg/g resin) displayed the greatest degree of hydrolytic activity against
      lyophilized Micrococcus lysodeikticus cell wall preparations. Enzymatic activity
      of immobilized lysozyme was 14.2% of that of the free enzyme. Preparations with
      longer spacers yielded higher total activity yet the retained activity was
      constant at about 14% level. A control that consisted of randomly coupled
      lysozyme to polystyrene beads without an amino acid spacer gave an enzyme
      activity of 158 U/g with a protein load of 1.24 mg/g resin which equated to 1.4%
      retained activity. Properties of the immobilized lysozyme system were studied,
      including stability and activity against soluble compared with insoluble
      substrates. A kinetics study of the immobilized lysozyme using Eadie-Hofstee plot
      parameters suggested significant external diffusion effects indicative of
      deviation from classic Michaelis-Menten kinetic behavior.

PMID- 18034731
TI  - Development of a sanitizing fabric wipe for use on food contact surfaces.
AB  - A sanitizer was incorporated into disposable sanitary wipes that were used to
      eliminate microorganisms on plastic and metal surfaces. These surfaces were
      inoculated with strains of Bacillus subtilis OSU 494, Enterococcus faecalis OSU
      48, Escherichia coli ATCC 29181, Listeria innocua ATCC 33090, Pseudomonas
      aeruginosa OSU 167, Salmonella enteritidis OSU 799, Staphylococcus epidermidis
      OSU 838), Candida albicans ATCC 10231, and Aspergillus fumigatus ATCC 10894.
      These inoculated surfaces were cleaned with the wipes for 5, 10, and 30 s, then
      organisms surviving on the cleaned surfaces and in the wipes were enumerated.
      Applying the sanitizing wipe to the plastic and metal surfaces reduced the
      viability of bacteria (> log 4 for 5 s), yeast cells (> log 5 for 10 s), and
      fungal spores (< log 4 for all times). The use of large pore sized or thick wipes
      showed better sanitizing result when compared with the use of the small pore
      sized and slim wipe. There were no significant differences (P > 0.05) between
      surviving numbers on the surface of the plastic compared with that of the metal.

PMID- 18034732
TI  - Acceleration of Thai fish sauce fermentation using proteinases and bacterial
      starter cultures.
AB  - A means to accelerate fish sauce fermentation without adversely affecting fish
      sauce quality was investigated. Starter cultures prepared from Virgibacillus sp.
      SK33, Virgibacillus sp. SK37, and Staphylococcus sp. SK1-1-5 were added
      separately to anchovy that was hydrolyzed by 0.25% Alcalase at 60 degrees C for 2
      h followed by 0.5% Flavourzyme at 50 degrees C for 4 h. The mixtures were then
      adjusted to contain 25% solar salt and incubated at 35 degrees C for 4 mo. alpha
      Amino contents of all inoculated samples were higher than the control (without
      the addition of starter culture) during the course of fermentation. After 4-mo
      fermentation, the samples inoculated with Staphylococcus sp. SK1-1-5 contained
      the highest alpha-amino content of 733.37 +/- 13.89 mM while that of the control
      was 682.67 +/- 3.33 mM. Amino acid profiles of inoculated samples showed similar
      patterns to that of commercial product fermented for 12 mo, with glutamic,
      aspartic, and lysine being predominant amino acids. Virgibacillus sp. SK33
      appeared to decrease histamine content of fish sauce by 50% when compared to the
      control. Volatile compounds analyzed by GC-MS of all inoculated samples fermented
      for 4 mo exhibited a similar pattern to those of the 12-mo-old commercial
      product. Samples inoculated with Staphylococcus sp. SK1-1-5 produced higher
      levels of volatile fatty acids and showed similar sensory characteristics to the
      commercial fish sauce fermented for 12 mo. Staphylococcus sp. SK1-1-5 is a
      potential strain that can be applied to produce fish sauce with overall sensory
      characteristics of traditional fish sauce in shorter time.

PMID- 18034733
TI  - Decontamination of Escherichia coli O157:H7 and Salmonella enterica on
      blueberries using ozone and pulsed UV-light.
AB  - Efficacy of gaseous ozone, aqueous ozone, and pulsed UV-light was evaluated for
      the purpose of decontaminating blueberries artificially contaminated with either
      Escherichia coli O157:H7 or Salmonella. Blueberries were exposed to 4 different
      gaseous ozone treatments: continuous ozone exposure, pressurized ozone exposure,
      and 2 combined treatments. Maximum reductions of Salmonella and E. coli O157:H7
      after 64-min pressurized or 64-min continuous exposure were 3.0 and 2.2 log(10)
      CFU/g, respectively. Aqueous ozone experiments were conducted at 20 degrees C and
      4 degrees C and zero plate counts were observed for E. coli O157:H7 and
      Salmonella after 64 min of ozone exposure at 20 degrees C. Finally, pulsed UV
      light was evaluated at 3 different distances from the light. Maximum reductions
      of 4.3 and 2.9 log(10) CFU/g were observed at 8 cm from the light after 60 s of
      treatment for Salmonella and E. coli O157:H7, respectively. A sensory analysis as
      well as color analysis was performed on blueberries from each treatment agent;
      neither analysis detected a difference between treated and untreated blueberries.
      The results presented in this study indicate that ozone and pulsed UV-light are
      good candidates for decontamination of blueberries.

PMID- 18034734
TI  - Antimicrobial effect of electrolyzed oxidizing water against Escherichia coli
      O157:H7 and Listeria monocytogenes on fresh strawberries (Fragaria x ananassa).
AB  - Antibacterial activity of electrolyzed oxidizing (EO) water prepared from 0.05%
      or 0.10% (w/v) sodium chloride (NaCl) solutions against indigenous bacteria
      associated with fresh strawberries (Fragaria x ananassa) was evaluated. The
      efficacy of EO water and sodium hypochlorite (NaOCl) solution in eliminating and
      controlling the growth of Listeria monocytogenes and Escherichia coli O157:H7
      inoculated onto strawberries stored at 4 +/- 1 degrees C up to 15 d was
      investigated at exposure time of 1, 5, or 10 min. Posttreatment neutralization of
      fruit surfaces was also determined. More than 2 log(10) CFU/g reductions of
      aerobic mesophiles were obtained in fruits washed for 10 or 15 min in EO water
      prepared from 0.10% (w/v) NaCl solution. Bactericidal activity of the
      disinfectants against L. monocytogenes and E. coli O157:H7 was not affected by
      posttreatment neutralization, and increasing exposure time did not significantly
      increase the antibacterial efficacy against both pathogens. While washing fruit
      surfaces with distilled water resulted in 1.90 and 1.27 log(10) CFU/mL of rinse
      fluid reduction of L. monocytogenes and E. coli O157:H7, respectively, >/= 2.60
      log(10) CFU/mL of rinse fluid reduction of L. monocytogenes and up to 2.35 and
      3.12 log(10) CFU/mL of rinse fluid reduction of E. coli O157:H7 were observed on
      fruit surfaces washed with EO water and NaOCl solution, respectively. Listeria
      monocytogenes and E. coli O157:H7 populations decreased over storage regardless
      of prior treatment. However, EO water and aqueous NaOCl did not show higher
      antimicrobial potential than water treatment during refrigeration storage.

PMID- 18034735
TI  - Hydrodynamic cavitation to improve bulk fluid to surface mass transfer in a
      nonimmersed ultraviolet system for minimal processing of opaque and transparent
      fluid foods.
AB  - Ultraviolet (UV)-induced chemical reactions and inactivation of microorganisms in
      transparent and opaque fluids are strongly dependent upon the homogenous exposure
      of the target species to the UV irradiation. Current UV technologies used in
      water disinfection and food preservation applications have limited efficacy due
      to suspended particles shading target species. An Ultraviolet-Shockwave Power
      Reactor (UV-SPR) consisting of an inner rotating rotor and a stationary quartz
      housing and 2 end plates was used to induce 'controlled cavitation.' Eight UV low
      pressure mercury lamps spaced uniformly were installed lengthwise around the
      quartz housing periphery. A KI to I(3) (-)chemical dosimeter for UV was used to
      quantify photons received by fluid in the annular space of the SPR. UV dose
      (J/m(2)) increased from 97 J/m(2) at 0 rpm to over 700 J/m(2) for SPR speeds
      above 2400 rpm. Inactivation of E. coli 25922 in apple juice and skim milk in the
      UV-SPR at exit temperatures below 45 degrees C was greater than 4.5 and 3 logs,
      respectively. The UV-SPR system proved successful in increasing the mass transfer
      of transparent and opaque fluid to the UV irradiated surface.

PMID- 18034736
TI  - Inactivation of food spoilage microorganisms by hydrodynamic cavitation to
      achieve pasteurization and sterilization of fluid foods.
AB  - Hydrodynamic cavitation is the formation of gas bubbles in a fluid due to
      pressure fluctuations induced by mechanical means. Various high-acid (pH <
      [corrected]/= 4.6) fluid foods were processed in a hydrodynamic cavitation
      reactor to determine if commercial sterility can be achieved at reduced
      processing temperatures. Sporicidal properties of the process were also tested on
      a low-acid (pH > [corrected] 4.6) fluid food. Fluid foods were pumped under
      pressure into a hydrodynamic cavitation reactor and subjected to 2 rotor speeds
      and flow rates to achieve 2 designated exit temperatures. Thermal inactivation
      kinetics were used to determine heat-induced lethality for all organisms. Calcium
      fortified apple juice processed at 3000 and 3600 rpm rotor speeds on the reactor
      went through a transient temperature change from 20 to 65.6 or 76.7 degrees C and
      the total process lethality exceeded 5-log reduction of Lactobacillus plantarum
      and Lactobacillus sakei cells, and Zygosaccharomyces bailii cells and ascospores.
      Tomato juice inoculated with Bacillus coagulans spores and processed at 3000 and
      3600 rpm rotor speeds endured a transient temperature from 37.8 to 93.3 or 104.4
      degrees C with viable CFU reductions of 0.88 and 3.10 log cycles, respectively.
      Skim milk inoculated with Clostridium sporogenes putrefactive anaerobe 3679
      spores and processed at 3000 or 3600 rpm rotor speeds endured a transient
      temperature from 48.9 to 104.4 or 115.6 degrees C with CFU reductions of 0.69 and
      2.84 log cycles, respectively. Utilizing hydrodynamic cavitation to obtain
      minimally processed pasteurized low-acid and commercially sterilized high-acid
      fluid foods is possible with appropriate process considerations for different
      products.

PMID- 18034737
TI  - Quality changes during refrigerated storage of MA-packaged pre-rigor fillets of
      farmed Atlantic cod (Gadus morhua L.) using traditional MAP, CO2 emitter, and
      vacuum.
AB  - Quality changes during 3 wk of refrigerated storage (1.3 degrees C) were studied
      on pre-rigor filleted farmed Atlantic cod packed in modified atmosphere (MAP, 60%
      CO2 and 40% O2) or vacuum. The packages of MAP contained either a CO2 emitter and
      low gas volume to product volume (g/p ratio) of 1.3, or a 3.9 g/p ratio and no
      emitter. The CO2 level remained stable or increased in the packages with CO2
      emitter, whereas the CO2 level in the packages with no CO2 emitter decreased to
      40% after 4 d of refrigerated storage. High levels of oxygen in the gas mixture
      prevented formation of trimethyl amine (TMA) during storage of the MA-packed
      fish, whereas the TMA content increased significantly after 10-d storage in
      vacuum. MA-packed samples had the highest values of 1-penten-3-ol. Sensory scores
      of sour, sulfur, and pungent odors were significantly higher for vacuum-packed
      cod compared to the 2 MA-packaging methods measured 14 d after slaughtering. No
      differences in sensory scores were observed between the 2 methods of MAP, and
      shelf life of these samples seemed to be 14 to 21 d. Cod samples packaged in
      vacuum packages had higher pH values compared to ordinary MAP and packages
      containing a CO2 emitter. Bacterial growth was inhibited by MAP and resulted at
      the end of the storage period in dominance of Carnobacterium and some
      Photobacterium. In MA packages with high O2 levels the Photobacterium was
      inhibited. It is concluded that CO2 emitters are well suited for reduction of
      transport volume for MA-packaged farmed cod.

PMID- 18034738
TI  - Fermentation of calcium-fortified soymilk with Lactobacillus: effects on calcium
      solubility, isoflavone conversion, and production of organic acids.
AB  - The objective of this study was to enhance calcium solubility and bioavailability
      from calcium-fortified soymilk by fermentation with 7 strains of Lactobacillus,
      namely, L. acidophilus ATCC 4962, ATCC33200, ATCC 4356, ATCC 4461, L. casei ASCC
      290, L. plantarum ASCC 276, and L. fermentum VRI-003. The parameters that were
      used are viability, pH, calcium solubility, organic acid, and biologically active
      isoflavone aglycone content. Calcium-fortified soymilk made from soy protein
      isolate was inoculated with these probiotic strains, incubated for 24 h at 37
      degrees C, then stored for 14 d at 4 degrees C. Soluble calcium was measured
      using atomic absorption spectrophotometry (AA). Organic acids and bioactive
      isoflavone aglycones, including diadzein, genistein, and glycetein, were measured
      using HPLC. Viability of the strains in the fermented calcium-fortified soymilk
      was > 8.5 log(10) CFU/g after 24 h fermentation and this was maintained for 14-d
      storage at 4 degrees C. After 24 h, there was a significant increase (P < 0.05)
      in soluble calcium. L. acidophilus ATCC 4962 and L. casei ASCC 290 demonstrated
      the highest increase with 89.3% and 87.0% soluble calcium after 24 h,
      respectively. The increase in calcium solubility observed was related to lowered
      pH associated with production of lactic and acetic acids. Fermentation
      significantly increased (P < 0.05) the level of conversion of isoflavones into
      biologically active aglycones, including diadzein, genistein, and glycetein. Our
      results show that fermenting calcium-fortified soymilk with the selected
      probiotics can potentially enhance the calcium bioavailability of calcium
      fortified soymilk due to increased calcium solubility and bioactive isoflavone
      aglycone enrichment.

PMID- 18034739
TI  - Synergistic antiyeast activity of garlic oil and allyl alcohol derived from
      alliin in garlic.
AB  - Garlic oil (GO) and allyl alcohol (AA), both derived from alliin in garlic using
      different preparation methods, cause potent growth inhibition in yeasts. GO and
      AA inhibited Candida utilis ATCC42416 in different ways: GO has fungistatic
      activity while AA has fungicidal activity. GO and AA have almost identical
      antimicrobial potencies against the indicator yeast, with minimum inhibitory
      concentrations of about 25 ppm when tested individually. When GO and AA were
      tested in combination, the antimicrobial efficacy significantly increased.
      Combinations of AA and GO at 1 and 9 ppm, 2 and 7 ppm, 5 and 5 ppm, and 6 and 3
      ppm, respectively, inhibited C. utilis completely. The sum of the fractional
      inhibitory concentrations (FICs) in the 2-component (GO and AA) combination was
      as low as 0.37 for C. utilis, indicating strong synergism. The sum of the FICs of
      diallyl disulfide and diallyl trisulfide in combination with AA was larger than
      that of the GO-AA combination, suggesting that the synergy was lower.

PMID- 18034740
TI  - Combined effect of aqueous chlorine dioxide and modified atmosphere packaging on
      inhibiting Salmonella Typhimurium and Listeria monocytogenes in mungbean sprouts.
AB  - This study was conducted to investigate the effect of chlorine dioxide (ClO2)
      combined with modified atmosphere packaging (MAP) on inhibiting total mesophilic
      microorganisms, Salmonella Typhimurium, and Listeria monocytogenes in mungbean
      sprouts during refrigerated storage. Mungbean sprouts were packaged using 4
      different methods (air, vacuum, CO2 gas, and N2 gas) following treatment with
      water or 100 ppm ClO2 for 5 min and stored at 5 +/- 2 degrees C. The population
      of total mesophilic microorganisms in mungbean sprouts was about 8.4-log(10)
      CFU/g and this level was not significantly reduced by treatment with water or
      ClO2 (P > 0.05). However, when samples were packaged under vacuum, N2 gas, or CO2
      gas following treatment with ClO2, the populations of total mesophilic
      microorganisms were significantly reduced during storage (P < 0.05). Levels of S.
      Typhimurium and L. monocytogenes in mungbean sprouts following inoculation were
      4.6- and 5.6-log(10) CFU/g and treatment with water followed by different
      packaging conditions (air, vacuum, N2 gas, and CO2 gas) had no significant effect
      on population reduction (P > 0.05). However, treatment with ClO2 significantly
      reduced populations of S. Typhimurium and L. monocytogenes by 3.0- and 1.5-log
      CFU/g, respectively (P < 0.05), and these reduced cell levels were maintained or
      decreased in samples packaged under vacuum or in N2 or CO2 gas during storage.
      These results suggest that the combination of ClO2 treatment and MAP such as CO2
      gas packaging may be useful for inhibiting microbial contamination and
      maintaining quality in mungbean sprouts during storage.

PMID- 18034741
TI  - Acid, bile, and heat tolerance of free and microencapsulated probiotic bacteria.
AB  - Eight strains of probiotic bacteria, including Lactobacillus rhamnosus,
      Bifidobacterium longum, L. salivarius, L. plantarum, L. acidophilus, L.
      paracasei, B. lactis type Bl-O4, and B. lactis type Bi-07, were studied for their
      acid, bile, and heat tolerance. Microencapsulation in alginate matrix was used to
      enhance survival of the bacteria in acid and bile as well as a brief exposure to
      heat. Free probiotic organisms were used as a control. The acid tolerance of
      probiotic organisms was tested using HCl in MRS broth over a 2-h incubation
      period. Bile tolerance was tested using 2 types of bile salts, oxgall and
      taurocholic acid, over an 8-h incubation period. Heat tolerance was tested by
      exposing the probiotic organisms to 65 degrees C for up to 1 h. Results indicated
      microencapsulated probiotic bacteria survived better (P < 0.05) than free
      probiotic bacteria in MRS containing HCl. When free probiotic bacteria were
      exposed to oxgall, viability was reduced by 6.51-log CFU/mL, whereas only 3.36
      log CFU/mL was lost in microencapsulated strains. At 30 min of heat treatment,
      microencapsulated probiotic bacteria survived with an average loss of only 4.17
      log CFU/mL, compared to 6.74-log CFU/mL loss with free probiotic bacteria.
      However, after 1 h of heating both free and microencapsulated probiotic strains
      showed similar losses in viability. Overall microencapsulation improved the
      survival of probiotic bacteria when exposed to acidic conditions, bile salts, and
      mild heat treatment.

PMID- 18034742
TI  - Nutritional and safety assessments of foods and feeds nutritionally improved
      through biotechnology: case studies: executive summary of a task force report by
      the International Life Sciences Institute, Washington, D.C.
AB  - During the last 2 decades, the public and private sectors have made substantial
      international research progress toward improving the nutritional value of a wide
      range of food and feed crops. Nevertheless, significant numbers of people still
      suffer from the effects of undernutrition. In addition, the nutritional quality
      of feed is often a limiting factor in livestock production systems, particularly
      those in developing countries. As newly developed crops with nutritionally
      improved traits come closer to being available to producers and consumers, we
      must ensure that scientifically sound and efficient processes are used to assess
      the safety and nutritional quality of these crops. Such processes will facilitate
      deploying these crops to those world areas with large numbers of people who need
      them. This document describes 5 case studies of crops with improved nutritional
      value. These case studies examine the principles and recommendations published by
      the Intl. Life Sciences Inst. (ILSI) in 2004 for the safety and nutritional
      assessment of foods and feeds derived from nutritionally improved crops (ILSI
      2004). One overarching conclusion that spans all 5 case studies is that the
      comparative safety assessment process is a valid approach. Such a process has
      been endorsed by many publications and organizations, including the 2004 ILSI
      publication. The type and extent of data that are appropriate for a
      scientifically sound comparative safety assessment are presented on a case-by
      case basis in a manner that takes into account scientific results published since
      the 2004 ILSI report. This report will appear in the January issue of
      Comprehensive Reviews in Food Science and Food Safety.

PMID- 18034743
TI  - Yerba Mate Tea (Ilex paraguariensis): a comprehensive review on chemistry, health
      implications, and technological considerations.
AB  - Yerba Mate tea, an infusion made from the leaves of the tree Ilex paraguariensis,
      is a widely consumed nonalcoholic beverage in South America which is gaining
      rapid introduction into the world market, either as tea itself or as ingredient
      in formulated foods or dietary supplements. The indigenous people have used it
      for centuries as a social and medicinal beverage. Yerba Mate has been shown to be
      hypocholesterolemic, hepatoprotective, central nervous system stimulant,
      diuretic, and to benefit the cardiovascular system. It has also been suggested
      for obesity management. Yerba Mate protects DNA from oxidation and in vitro low
      density lipoprotein lipoperoxidation and has a high antioxidant capacity. It has
      also been reported that Yerba Mate tea is associated to both the prevention and
      the cause of some types of cancers. Yerba Mate has gained public attention
      outside of South America, namely the United States and Europe, and research on
      this tea has been expanding. This review presents the usage, chemistry,
      biological activities, health effects, and some technological considerations for
      processing of Yerba Mate tea. Furthermore, it assesses in a concise and
      comprehensive way the potential of Ilex paraguariensis as a source of biological
      compounds for the nutraceutical industry.

PMID- 18034744
TI  - Calcium fortificants: overview and strategies for improving calcium nutriture of
      the U.S. population.
AB  - Despite more than 20 y of awareness of the importance of calcium to health, U.S.
      calcium intakes remain suboptimal. Fortification of foods with shortfall
      nutrients is probably the optimal strategy for dealing with widespread nutrient
      deficiencies, as it has the best chance of reaching the population segments most
      at risk, as contrasted with attempts at changing individuals' food choices or
      relying on voluntary supplement taking. Given the wide array of potential calcium
      fortificants and fortification levels, there is not much to guide manufacturers
      interested in improving the nutritional value of their products. In this review,
      we assemble the calcium salts/complexes that have been used or proposed for use
      as fortificants and describe certain of their measured characteristics that
      relate to incorporation into foods, particularly what is known of their
      absorbability. The calcium salts most commonly used as supplements or
      fortificants exhibit similar absorbability when tested in pure chemical form.
      Choice of salt will depend mainly upon cost, compatability with the manufacturing
      process, and consumer acceptability. However, interaction with food, tablet, or
      beverage matrices can degrade intrinsic absorbability substantially. As a
      consequence, each product must be explicitly tested to establish the degree to
      which its calcium is available to consumers.

PMID- 18034745
TI  - An integrated approach to evaluate food antioxidant capacity.
AB  - Many methods are available for determining food antioxidant capacity, which is an
      important topic in food and nutrition research and marketing. However, the
      results and inferences from different methods may vary substantially because each
      complex chemical reaction generates unique values. To get a complete and dynamic
      picture of the ranking of food antioxidant capacity, relative antioxidant
      capacity index (RACI), a hypothetical concept, is created from the perspective of
      statistics by integrating the antioxidant capacity values generated from
      different in vitro methods. RACI is the mean value of standard scores transformed
      from the initial data generated with different methods for each food item. By
      comparing the antioxidant capacity of 20 commonly consumed vegetables in the U.S.
      market that were measured with 7 chemical methods, we demonstrated that the RACI
      correlated strongly with each method. The significant correlation of RACI with an
      independent data set further confirmed that RACI is a valid tool to assess food
      antioxidant capacity. The key advantage of this integrated approach is that RACI
      is in a numerical scale with no units and has consistent agreement with chemical
      methods. Although it is a relative index and may not represent a specific
      antioxidant property of different food items, RACI provides a reasonably accurate
      rank of antioxidant capacity among foods. Therefore, it can be used as an
      integrated approach to evaluate food antioxidant capacity.

PMID- 18034746
TI  - Effect of winemaking practices on color indexes and selected bioactive phenolics
      of Aglianico wine.
AB  - Phenolic compounds are responsible for the sensory properties of wine as well as
      the properties beneficial to human health. The objective of this study was to
      establish the effect of the use of SO2 and pectolitic enzymes in the
      prefermentative phase, maceration time, and oak aging on color, anthocyanins,
      tannins, (+)-catechin, (-)-epicatechin, rutin, trans-resveratrol, and quercetin
      content of Aglianico wine. Color indexes and phenolics were analyzed by HPLC and
      spectrophotometric methods. The addition of SO2 and pectolitic enzymes before
      fermentation caused an increase in color intensity, color stability, total
      phenolics, anthocyanins, (+)-catechin, (-)-epicatechin rutin, trans-resveratrol,
      and quercetin content in Aglianico wine. Longer maceration times gave wines
      richer in total phenolics and with better chromatic characteristics. Storage in
      oak caused a decrease in anthocyanins, (+)-catechin, (-)-epicatechin, trans
      resveratrol, and quercetin content but an increase in total phenolic content, and
      a stabilizing effect on color also occurred.

PMID- 18034747
TI  - Energy content, sensory properties, and microbiological shelf life of German
      bologna-type sausages produced with citrate or phosphate and with inulin as fat
      replacer.
AB  - The aim of this study was to determine the feasibility of reducing energy content
      (9% to 48%) in bologna-type sausages by replacing fat with inulin and to study
      the effects of substituting citrate for phosphate in the traditional sausage
      formula. German-type mortadella was produced, and fat was replaced with
      increasing amounts of inulin as a frozen gel to yield 3%, 6%, 9%, and 12% inulin
      in the final product. In another part of the study, citrate was substituted for
      the phosphate in the recipe. All sausages produced were sliced, packaged under a
      modified atmosphere (70% N(2), 30% CO(2)), and stored for 23 d at +7 degrees C.
      Sausage quality was determined by chemical and instrumental texture profile
      analyses, color measurement, sensory evaluation, and microbiological testing.
      Replacing fat with inulin led to significant energy content reductions of up to
      47.5% (with 12% inulin). However, the sensory properties of these sausages were
      also different from those of the control mortadella: fracturability fell,
      hardness and adhesiveness rose, and color became darker. In general, the
      substitution of citrate for phosphate significantly reduced the negative effects
      of inulin. There were no significant differences in microbiological stability
      between different inulin batches but there were significant differences between
      phosphate and citrate batches. Overall, the energy content of bologna-type
      sausages produced with citrate and with up to 6% inulin as a fat replacer was 22%
      lower than that of the control sausages. Furthermore, the sensory attributes
      (texture, color) of these 6% inulin-citrate sausages were comparable to the
      control sausages, and the sausages were microbiologically stable for 23 d of
      storage.

PMID- 18034748
TI  - The sensory interactions of organic acids and various flavors in ramen soup
      systems.
AB  - This study was conducted to investigate the sensory interactions between various
      organic acids and flavorants in 3 types of ramen soup ('beef,' seafood, and
      'kimchi') when types and levels of organic acids (citric, malic, and lactic)
      varied. For 'beef' and seafood ramen soup, weak suprathreshold levels of acids
      (0.0039% to 0.0071%) were applied to the system and medium suprathreshold of
      acids (0.0128% to 0.0299%) were applied to the kimchi ramen soup. The amount of
      acid applied to each system was chosen based on the equiweight level. Descriptive
      analyses were performed separately for each ramen soup system using 8 trained
      panelists. A total of 11, 13, and 12 flavor descriptors were generated for
      'beef,' seafood, and 'kimchi' soup, respectively. Analysis of variance was
      conducted to evaluate the effect of organic acid on the sensory characteristics
      of ramen soup. Principal component analysis was conducted to summarize the
      relationship between the soup samples and attributes. The effect of organic acids
      on the flavor attributes of ramen soup was dependent on the soup system as well
      as adding levels of acid. Addition of lactic acid power (at 0.0066%) in
      'beef'ramen soup showed enhancement effect on the sour, salty, beefy, 'mushroom'
      flavor, and fermented soybean paste soup flavor, whereas lactic acid powder (at
      0.0071%) showed enhancement effect only on the sour and fermented soybean paste
      soup flavor in seafood ramen soup due to the strong 'hot' flavor characteristics
      of the soup. In kimchi ramen soup, flavor attributes congruent to sourness were
      enhanced by the addition of organic acids to the system.

PMID- 18034749
TI  - Effect of pectin enhancement on plasma quercetin and fecal flora in rutin
      supplemented mice.
AB  - Few reports have considered the effects of dietary fiber on plasma quercetin and
      the intestinal flora. We investigated the effects of pectin on the plasma and
      fecal flora of mice fed a diet supplemented with the quercetin glycoside rutin.
      Male mice were randomly divided into 2 groups, which were fed a pectin-rutin (PR)
      or cellulose-rutin (CR) diet for 14 d. Plasma quercetin and isorhamnetin
      metabolites were measured by high-performance liquid chromatography. Feces were
      immediately processed with bacteriological procedures. The fecal flora was
      investigated. Plasma quercetin and isorhamnetin concentrations were significantly
      higher in the PR diet group, as was the plasma isorhamnetin/quercetin ratio. The
      composition of the intestinal flora differed between the 2 dietary groups. The
      total number of fecal bacteria was significantly larger in the PR group, in which
      most types of bacteria were more abundant, with the exceptions of bifidobacteria,
      fusiform-shaped bacteria, and staphylococci. The lower gut seemed to be the major
      absorption site for rutin. Pectin might thus enhance the bioavailability of
      quercetin from rutin by altering the metabolic activity of the intestinal flora
      and/or gut physiological function.

PMID- 18034750
TI  - Heat-moisture treatment of high-amylose corn starch increases dietary fiber
      content and lowers plasma cholesterol in ovariectomized rats.
AB  - The effect of dietary high-amylose corn starch (HACS) of varying dietary fiber
      (DF) content on plasma cholesterol was examined in ovariectomized (OVX) rats.
      Gelatinized normal corn starch (G-CS) was used as a reference. OVX rats were fed
      a fiber-free purified diet containing G-CS, HACS, gelatinized high-amylose corn
      starch (G-HACS), or heat-moisture treated HACS (HM-HACS) at 400 g starch/kg diet
      for 21 d. The DF content of G-CS, HACS, G-HACS, and HM-HACS measured by the AOAC
      method was 0.1, 19.3, 2.4, and 64.5 g/100 g, respectively. The dry weight of
      cecal contents, cecal wall weight, the amount of short chain fatty acids in cecal
      contents, the amount of bile acids in small intestinal contents, and fecal
      excretion of neutral sterols increased logarithmically with increasing DF, while
      total plasma cholesterol concentration decreased. On the other hand, hepatic
      CYP7A1 activity, fecal dry weight, and fecal excretion of bile acids increased
      linearly with increasing DF, while body weight gain decreased. The
      hypocholesterolemic effect of HACS in OVX-rats appeared to be more effective by
      heat-moisture treatment.

PMID- 18034751
TI  - Fresh pasta quality as affected by enrichment of nonstarch polysaccharides.
AB  - Nonstarch polysaccharides (NSPs), both soluble and insoluble, were added to pasta
      doughs at levels of 2.5%, 5%, 7.5%, and 10% levels. The cooking and textural
      characteristics of the pastas were evaluated using a range of analytical
      techniques. Generally, NSP addition was found to increase the cooking losses, and
      reduce the protein and starch contents of the pasta. This effect was dependent on
      the level of NSP added and also the type (soluble or insoluble). Pasta firmness
      was generally reduced in relation to the level of NSP addition, although some gel
      forming NSPs resulted in higher firmness values. Pasta stickiness, adhesiveness,
      and elasticity were also affected. The results indicate that careful selection of
      NSP addition is needed to ensure optimum textural and cooking characteristics in
      NSP enriched pasta products.

PMID- 18034752
TI  - Chocolate milk and the Hispanic consumer.
AB  - The U.S. Hispanic population is increasing, and purchasing power of this group is
      also increasing. Little is known about the attitudes and preferences of Hispanic
      adults or children toward chocolate milk. The objective of this study was to
      understand Hispanic consumer attitudes and preferences for chocolate milk. Focus
      groups with Hispanic adults (> 18 y, 3 groups, n= 31) and children (10 to 14 y, 6
      groups, n= 29) were conducted to gain qualitative insight into perceptions and
      consumption trends. Using focus group results and descriptive analysis profiles
      of chocolate milks, 5 representative chocolate milks were selected for
      quantitative consumer testing. Milks were evaluated for overall liking and other
      attributes by Hispanic adults (n= 79), Caucasian adults (n= 91), and Hispanic
      children (n= 45). Analysis of variance and internal and external preference
      mapping were conducted to characterize differences among treatments and ethnic
      groups. Chocolate milks were differentiated by descriptive analysis (P < 0.001)
      in visual, flavor, and mouthfeel attributes. Hispanic children (n= 45) rated all
      chocolate milks higher in liking than Hispanic or Caucasian adults, and
      documented significant differences in liking for milks evaluated (P < 0.05).
      Caucasians adults were generally more discriminatory in liking of chocolate milks
      than Hispanic adults, but consistent ethnic differences were observed only for
      chocolate flavor liking where Hispanics assigned higher chocolate flavor liking
      scores to milks compared to Caucasians. Three consumer clusters were identified
      and the drivers for these clusters were largely consistent with previous
      chocolate milk consumer studies in that many of the same key drivers of liking
      for chocolate milk were identified. The results indicated that these consumer
      clusters were not defined exclusively by ethnicity.

PMID- 18034753
TI  - Cross-cultural comparisons among the sensory characteristics of fermented soybean
      using Korean and Japanese descriptive analysis panels.
AB  - One of the most important initial steps in exporting a food product to another
      country from the R&D perspective is to describe and translate the sensory
      characteristics of a food product appropriately into the language of the target
      country. The objectives of this study were to describe and compare the sensory
      characteristics of Korean and Japanese style fermented soybean products, and to
      cross-culturally compare the lexicons of the identical product generated by the
      Korean and Japanese panelists. Four types of Korean and 4 types of Japanese style
      fermented soybean consisting of whole bean type and paste type were analyzed. Ten
      Korean and 9 Japanese panelists were recruited in Korea. Two separate descriptive
      analyses were conducted, with the panelists differing in their country of origin.
      Each group was trained, developed lexicon, and conducted descriptive analysis
      independently. Analysis of variance and various multivariate analyses were
      applied to delineate the sensory characteristics of the samples and to compare
      the cross-cultural differences in the usage of lexicon. The Korean and Japanese
      panelists generated 48 and 36 sensory attributes, respectively. Cross-cultural
      consensus was shown for evaluating the whole bean type fermented soybean and
      white miso, which were relatively distinctive samples. However, for the less
      distinctive samples, the panelists tend to rate higher in negative attributes for
      the fermented soybeans that originated from the other country. The Japanese
      panelists grouped the samples by their country of origin and soy sauce flavor was
      the main attribute for cross-cultural differentiation. However, the Korean
      panelists did not make a cross-cultural distinction among the samples.

PMID- 18034754
TI  - Zinc and iron bioavailability of genetically modified soybeans in rats.
AB  - The aim of this work was to evaluate zinc and iron bioavailability of UFV-116, a
      new variety without 2 lipoxygenases, with better taste and flavor than a
      commercial variety OCEPAR 19, containing all 3 isozymes. To evaluate zinc
      absorption using 65Zn whole body retention and femur 65Zn uptake, rats were given
      3 g of a 65ZnCl2 labeled test meal (0.25 microCi). The 2 varieties were tested at
      the level of 9 and 30 ppm of zinc as defatted soy flour. Two other groups
      (control) received egg white as source of protein and ZnS04.H20 as the zinc
      source. To evaluate iron absorption, using 59Fe whole body retention, animals
      were given a 3 g 59FeCl3 labeled test meal (0.2 microCi). The 2 varieties were
      tested at 12 and 25 ppm iron as defatted soy flour. Whole fat soy flour of
      variety 1 (UFV-116) was higher (P < 0.05) in Ca, K, Mg, phytic acid, and oxalate
      than variety 2 (OCEPAR-19). No difference was observed among the soybean
      varieties (P > 0.05) for femur 65Zn retention, at different levels of zinc.
      However, whole body retention was lower (P < 0.05) for UFV-116 than for OCEPAR
      19. Femur 65Zn uptake was correlated with the whole body retention; however,
      whole body retention was more sensitive. Whole body 59Fe retention from UFV-116
      was lower (P < 0.05) than from OCEPAR-19. Zinc and iron bioavailability was lower
      for UFV-116, possibly due to its higher content of antinutrient factors,
      especially phytate.

PMID- 18034755
TI  - Major phenolic acids and total antioxidant activity in Mamaki leaves, Pipturus
      albidus.
AB  - Three phenolic acids, (+)catechins, chlorogenic acid, and rutin, were identified
      and quantified in Mamaki leaves using a liquid chromatograph-mass spectrometer
      technique. Concentrations of (+)catechins, chlorogenic acid, and rutin varied
      from 1.1 to 5.0 mg/g of Mamaki leaves as determined in the extract using 0.5%
      acetic acid in 90% aqueous methanol. This study also quantified total antioxidant
      capacity using the photochemiluminescence method, which was expressed in
      equivalents to ascorbic acid (AA). Mamaki teas brewed for 30 min contained total
      antioxidant activity (TAA) between 238 and 259 mg AA/g of tea. Mamaki teas brewed
      for 1 h and stored at 4 h, 1 d, and 3 d at 4 degrees C had available TAA 293,
      271, 172, and 163 mg AA/g of tea leaves, respectively. The concentrations of
      (+)catechins and rutin in Mamaki leaves are compared to other types of popular
      teas. Mamaki teas contained relatively low amounts of TAA compared to green teas
      and Lipton teas.

PMID- 18034756
TI  - Angiotensin-I converting enzyme inhibitory peptide derived from porcine skeletal
      muscle myosin and its antihypertensive activity in spontaneously hypertensive
      rats.
AB  - Crude myosin light chain was extracted from Japanese domestic pork loin and
      digested with pepsin. Antihypertensive peptide was isolated from this digest as a
      measure of its inhibitory activity for angiotensin-I converting enzyme (ACE).
      Through isolation with some chromatographies, a single active fraction was
      isolated, and it was detected as an octapeptide, Val-Lys-Lys-Val-Leu-Gly-Asn-Pro,
      from 47th to 54th positions of myosin light chain. The 50% inhibitory
      concentration of this peptide was 28.5 muM. Kinetic evaluation showed that this
      peptide was a noncompetitive inhibitor, but it was slowly hydrolyzed by ACE. At
      the dose of 10 mg/kg, this peptide showed antihypertensive activity after a
      maximum of 3 h of administration and was estimated as a temporally effective
      hypotensor.

PMID- 18034757
TI  - Sensory and instrumental analysis for slipperiness and compliance of food during
      swallowing.
AB  - In spite of its importance, there have been few attempts to evaluate the sensory
      attributes of the food bolus during swallowing. In the current study, the
      slipperiness, the degree of slide for the food bolus through the mucosal surface
      of the oro-pharynx, and the compliance, how easily the shape of a food bolus can
      be transformed for automatic and comfortable swallowing, were derived among
      several sensory attributes related to the swallowing. Therefore, the study aims
      were twofold: (1) to develop the methods of sensory and instrumental analyses for
      determining the slipperiness and compliance of the food bolus during swallowing
      and (2) to examine the appropriateness of the newly designed devices by
      correlating the data between the sensory and instrumental analyses. Six
      commercial food products were evaluated by 10 trained panelists for each
      attribute. The devices for assessing each attribute were developed in
      consideration of the oro-pharyngeal movements. The sensory and instrumental
      analyses showed high correlation and regression coefficients as well as intensity
      differences of the 6 samples for each attribute. In conclusion, the slipperiness
      and the compliance were suitable for acquiring a better understanding of the
      sensory attributes of the food bolus during swallowing, and the newly developed
      devices showed a high potential for determining those attributes.

PMID- 18034758
TI  - The effect of frequency of consumption of artificial sweeteners on sweetness
      liking by women.
AB  - Research into sweetness perception and preference thus far has demonstrated that
      sweetness preference is related not to the total sugar consumed by an individual
      but the amount of refined sugar ingested. Research has yet to be conducted,
      however, to determine whether a diet high in artificial sweeteners contributes to
      sweetness liking and preference with the same result as a diet high in sugar. The
      purpose of this research was to determine if such a relationship exists with
      regard to diets high in artificially sweetened beverages. Seventy-one female
      participants were recruited and screened for sweetener consumption in beverages.
      Sixty-four of these individuals were selected for sensory testing. All
      participants evaluated orange juice samples (ranging from 0% added sucrose to 20%
      added sucrose) for liking of sweetness using a 9-point hedonic scale. Based on
      screening survey data, participants were categorized according to sweetener
      consumption group (artificial sweetener consumers and natural sweetener
      consumers) and by overall sweetened beverage intake (low or high, regardless of
      sweetener type normally consumed). Sensory data were analyzed to compare
      sweetness liking in each of these groups. Significant differences in liking were
      observed, with individuals in the high sweetened beverage intake group preferring
      sweeter orange juice than those in the low-intake group. Categorization by
      sweetener type resulted in no significant differences between the groups,
      indicating that regardless of the type of sweetener consumed in a beverage,
      liking of sweetness will be influenced in the same manner.

PMID- 18034759
TI  - Antiallergic activities of pigmented rice bran extracts in cell assays.
AB  - Using a panel of chemical, biochemical, and cell assays, we determined inhibitory
      effects of extracts of the pigmented black rice brans on in vitro allergic
      reactions. Ethanol-water (70% v/v) extracts from 5 pigmented brans were found to
      be more effective than an extract from a nonpigmented rice cultivar in
      suppressing the release of histamine and beta-hexosaminidase from basophilic RBL
      2H3 cells stimulated with both Ionophore A23187 and immunoglobulin E (IgE)
      antigen complexes. Suppression was also obtained with A23187-stimulated rat
      peritoneal mast cells. The extent of inhibition of these 2 markers of the immune
      response was accompanied by an influx of calcium ions. The inhibition of the
      immune process by the pigmented brans was confirmed by the observed modulation of
      the proinflammatory cytokine gene expressions and cytokine release, as indicated
      by the reduction in tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL
      4, and IL-6 mRNA expressions determined with the reverse transcription-polymerase
      chain reaction (RT-PCR). Reduction of TNF-alpha, IL-1beta, and IL-6 protein
      release from both the cultured cell line and peritoneal cells was further
      confirmed by enzyme-linked immunoadsorbent assays. Rice bran from the LK1-3-6-12
      1-1 cultivar was the most effective inhibitor in all assays. This particular rice
      variety merits further evaluation as part of a human diet to ascertain its
      potential to protect against allergic diseases such as hay fever and asthma.

PMID- 18034760
TI  - Identifying drivers for consumer acceptance and purchase intent of corn tortilla.
AB  - The traditional production of corn tortilla has been modified by new processing
      technologies to make possible a commercial-scale production; this practice has
      resulted in products having sensory properties different from those produced by
      the traditional method. There is no published information on sensory attributes
      driving acceptance and purchase intent of corn tortillas. Identifying sensory
      drivers for acceptance and purchase intent of corn tortillas will help
      commercially produce products that satisfy consumers' expectations. A consumer
      study was conducted to evaluate acceptance and purchase intent of corn tortillas
      and determine drivers of acceptance and purchase intent of the products. Ten
      samples of corn tortillas were selected to represent a variety of corn tortillas
      available in the Mexican market. Three hundred Mexican consumers evaluated
      acceptability of appearance, color, thickness, rollability, resistance to
      tearing, aroma, chewiness, taste and aftertaste, and overall liking using a 9
      point hedonic scale. Overall acceptance and purchase intent were determined with
      a yes/no scale. Analysis of variance and multivariate analysis of variance
      revealed that consumers were able to differentiate differences in sensory
      acceptability among 10 samples. For example, 2 homemade and 1 small commercial
      scale samples, with an overall liking score of 6.6 to 6.7, were more acceptable
      than others. Rollability, resistance to tearing, and chewiness were attributes
      underlying overall differences among 10 samples. Attributes determining overall
      acceptance of corn tortillas were chewiness and overall liking. Purchase intent
      was influenced by overall appearance, rollability, chewiness, taste, and overall
      liking. This study revealed critical sensory attributes and their weights given
      by Mexican consumers when making decisions for acceptance and purchase intent of
      corn tortilla.

PMID- 18034763
TI  - Indefinite anticoagulation after a first episode of unprovoked venous
      thromboembolism: yes.

PMID- 18034764
TI  - Usefulness of PFA-100 testing in the diagnostic screening of patients with
      suspected abnormalities of hemostasis: comparison with the bleeding time.
AB  - BACKGROUND: Global tests of hemostasis that are used to screen patients with
      clinical suspicion of bleeding disorders should help the physician to identify
      the phase of the hemostatic system that is abnormal and guide further diagnostic
      workup. PATIENTS AND METHODS: We compared the performance of Platelet Function
      Analyzer-100 (PFA-100) closure time (CT) with bleeding time (BT), both of which
      are screening tests for primary hemostasis, in the diagnostic workup of 128
      consecutive patients who were screened for bleeding disorders. The sensitivities
      of BT and PFA-100 CT for known defects of hemostasis were evaluated; in addition,
      we calculated their correlation with the levels of severity of the bleeding
      symptoms, which were recorded using a standardized questionnaire. RESULTS: The
      sensitivity of PFA-100 testing was 71% for von Willebrand disease (VWD) [with
      both collagen-adenosine diphosphate (C-ADP) and collagen-epinephrine (C-EPI)
      cartridges]; 58% (C-EPI) and 8% (C-ADP) for platelet function disorders (PFDs);
      and the sensitivity of BT was 29% (VWD) and 33% (PFD). C-EPI CT was also
      prolonged in about 20% of patients with abnormalities of coagulation or
      fibrinolysis. Only the C-EPI CT was significantly associated with the levels of
      severity of the patients' bleeding scores. CONCLUSIONS: BT and C-EPI are
      insufficiently sensitive to be recommended as hemostasis screening tests. The C
      ADP cartridge, which is sensitive to VWD only, might prove useful in further
      diagnostic workup of defects of primary hemostasis. The association of C-EPI CT
      with the severity of bleeding symptoms as a useful predictor of risk of bleeding
      in clinical practise should be tested in properly designed studies.

PMID- 18034765
TI  - T-cell responses over time in a mild hemophilia A inhibitor subject: epitope
      identification and transient immunogenicity of the corresponding self-peptide.
AB  - BACKGROUND: Antibodies that neutralize factor (F) VIII activity, clinically
      referred to as 'inhibitors', complicate the treatment of hemophilia A patients;
      current tolerance and bypass strategies are extremely costly and sometimes
      ineffective. The development of inhibitors requires T-cell help. OBJECTIVES: We
      characterized T-cell responses of a subject with mild hemophilia A with missense
      genotype A2201P for one year following his initial inhibitor response, with the
      goals of defining the primary epitope(s) and its (their) MHC Class II
      restriction. We investigated the possible involvement of regulatory T cells in
      modulating immune responses. PATIENTS/METHODS: The subject developed high-titer
      FVIII-neutralizing antibodies (250 BU mL(-1)) that declined over time to 8 BU ml(
      1). His clotting activity was initially impaired (3%) but returned to baseline (8
      10%) within four weeks. MHC Class II tetramers were used to analyze his CD4 T
      cells, which were stimulated with peptides spanning the C2 domain. Responses of
      total and CD25-depleted CD4 cells to sequences containing A2201 (native), P2201
      (hemophilic), and other predicted T-cell epitopes were evaluated. RESULTS AND
      CONCLUSIONS: An HLA-DRA-DRB1*0101 restricted T-cell epitope containing the wild
      type A2201 sequence was identified. Interestingly, peptides containing A2201 were
      recognized by CD4 T cells at all time points, whereas a P2201 peptide was
      recognized only near the initial peak response. The responsiveness of CD25
      depleted CD4 cells to an A2201 peptide was enhanced 11 and 19 weeks following
      inhibitor detection, suggesting the possible involvement of CD4+CD25+ regulatory
      T cells in modulating immune responses. Patient-derived T-cell clones
      proliferated in response to C2 protein and to peptides containing A2201 but not
      P2201.

PMID- 18034766
TI  - Tranexamic acid combined with recombinant factor VIII increases clot resistance
      to accelerated fibrinolysis in severe hemophilia A.
AB  - BACKGROUND: Most patients with severe hemophilia A suffer from a profoundly
      compromised hemostatic response. In addition to both the delayed and slow
      development of a clot, previous studies have documented that severe hemophilia A
      is also associated with reduced clot stability. OBJECTIVES: We examined whether
      the clot stability in hemophiliacs could be improved by treatment with tranexamic
      acid (TXA) in combination with recombinant factor VIII (rFVIII).
      PATIENTS/METHODS: Baseline blood samples were obtained from eight males with
      severe hemophilia A. Thereafter, a bolus injection of rFVIII was administered to
      increase the functional level of FVIII to approximately 50%. After 10 min, blood
      was collected followed by an intravenous injection of TXA. A third blood sample
      was obtained after a further 10 min. Whole blood clotting profiles were
      determined by thrombelastography using minimal tissue factor activation. Clot
      formation was assessed by both clot initiation and clot propagation. At clot
      termination, the maximum clot firmness and area under the elasticity curve were
      used to illustrate clot stability. Tissue-plasminogen activator was included in
      those experiments designed to assess clot stability. RESULTS: As expected, rFVIII
      increased clot formation, whereas TXA had no effect upon this parameter. Assays
      including tissue-plasminogen activator revealed that rFVIII increased the maximum
      clot firmness 3-fold; whereas the presence of TXA induced an additional 4-fold
      increase. The area under the elasticity curve increased 5-fold after rFVIII and
      24-fold after addition of TXA. CONCLUSIONS: The study demonstrates that
      simultaneous treatment with TXA and rFVIII significantly improves the clot
      stability in patients with hemophilia A.

PMID- 18034767
TI  - Anti-beta 2 glycoprotein I antibodies and the risk of myocardial infarction in
      young premenopausal women.
AB  - BACKGROUND: Contrasting data have been reported on the association between the
      presence of anti-phospholipid antibodies (aPL) and arterial thrombotic events,
      particularly those in coronary arteries. This discrepancy is perhaps related to
      the confounding effect of traditional risk factors. Among them, coronary
      atherosclerosis appears to be the most important in studies conducted in middle
      aged and elderly patients. OBJECTIVE: To minimize such confounding effects, a
      multicenter case-control study on the association between aPL and myocardial
      infarction (MI) was carried out in a rare cohort of young premenopausal women.
      METHODS: We evaluated 172 cases hospitalized for a first MI before the age of 45
      years and 172 controls individually matched with cases for age, sex and
      geographical origin. Clinical and laboratory data were collected and levels of
      anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI) and anti
      nuclear antibodies (ANA) were measured. RESULTS: A significant association
      between MI and IgG/IgM anti-beta2GPI antibodies was observed; the results were
      confirmed after adjusting for smoking and hypertension (anti-beta2GPI IgG OR =
      2.47, 95% CI 1.81-3.38; anti-beta2GPI IgM 4th quartile OR 3.68, 95% CI 1.69
      8.02). The association between anti-beta2GPI antibodies and MI was detected in
      both subgroups with and without coronary artery stenosis. Whereas the association
      of aCL IgG with MI was modest, ANA showed no significant association with MI. No
      aPL were found in unselected patients (mainly males) who recently developed acute
      MI. CONCLUSIONS: Anti-beta2GPI antibodies are a significant risk factor for MI in
      young premenopausal women independently of other risk factors, including the
      degree of coronary artery stenosis.

PMID- 18034768
TI  - Thromboprophylaxis for catheter-related thrombosis in patients with cancer: a
      systematic review of the randomized, controlled trials.

PMID- 18034769
TI  - Three different patterns of calibrated automated thrombogram obtained with six
      different anticoagulants.

PMID- 18034770
TI  - Double-blind studies are not always optimum for evaluation of a novel therapy:
      the case of new anticoagulants.

PMID- 18034771
TI  - Chilling induces a decrease in pyrophosphate-dependent H+-accumulation associated
      with a DeltapH(vac)-stat in mung bean, a chill-sensitive plant.
AB  - Chilling leads to cytoplasmic acidification in chill-sensitive plants. A possible
      explanation for this observation is that a DeltapH-stat between the cytosol and
      vacuole (DeltapH(vac)-stat) is perturbed by chilling. To understand the nature of
      this DeltapH(vac)-stat, the effect of temperature, between 20 and 0 degrees C, on
      pyrophosphate (PPi)- or ATP-dependent acidification of vacuolar vesicles,
      isolated from mung bean hypocotyls, was determined. Over the temperature range
      investigated, the H+-influx mediated by PPase was balanced with the H+-efflux,
      which was PPi-dependently suppressed, and consequently a constant pH in vesicles
      (pH(in)) of ca. 5 was maintained against temperature changes. However, the
      DeltapH(in) driven by ATP decreased as the temperature dropped. Thus, the PPi
      dependent H+-accumulation may function as an essential factor to form a
      DeltapH(vac)-stat against temperature changes. Next, to study the chilling
      sensitivity of PPi-dependent H+-accumulation, vacuolar vesicles were isolated
      from control seedlings or from seedlings chilled at 0 degrees C for 1 d. Chilling
      treatment resulted in a decrease in the H+-accumulation rate and in the steady
      state DeltapH(in) formed by PPi, the causes of which were enhanced by PPi
      dependent H+-efflux and reduced by H+-influx driven by PPase. Together, the
      results suggest that the decrease of PPi-dependent H+-accumulation associated
      with the DeltapH(vac)-stat could result in cytoplasmic acidification.

PMID- 18034772
TI  - Nitric oxide synthesis and signalling in plants.
AB  - As with all organisms, plants must respond to a plethora of external
      environmental cues. Individual plant cells must also perceive and respond to a
      wide range of internal signals. It is now well-accepted that nitric oxide (NO) is
      a component of the repertoire of signals that a plant uses to both thrive and
      survive. Recent experimental data have shown, or at least implicated, the
      involvement of NO in reproductive processes, control of development and in the
      regulation of physiological responses such as stomatal closure. However, although
      studies concerning NO synthesis and signalling in animals are well-advanced, in
      plants there are still fundamental questions concerning how NO is produced and
      used that need to be answered. For example, there is a range of potential NO
      generating enzymes in plants, but no obvious plant nitric oxide synthase (NOS)
      homolog has yet been identified. Some studies have shown the importance of NOS
      like enzymes in mediating NO responses in plants, while other studies suggest
      that the enzyme nitrate reductase (NR) is more important. Still, more published
      work suggests the involvement of completely different enzymes in plant NO
      synthesis. Similarly, it is not always clear how NO mediates its responses.
      Although it appears that in plants, as in animals, NO can lead to an increase in
      the signal cGMP which leads to altered ion channel activity and gene expression,
      it is not understood how this actually occurs. NO is a relatively reactive
      compound, and it is not always easy to study. Furthermore, its biological
      activity needs to be considered in conjunction with that of other compounds such
      as reactive oxygen species (ROS) which can have a profound effect on both its
      accumulation and function. In this paper, we will review the present
      understanding of how NO is produced in plants, how it is removed when its signal
      is no longer required and how it may be both perceived and acted upon.

PMID- 18034773
TI  - A comparison of ammonium, nitrate and proton net fluxes along seedling roots of
      Douglas-fir and lodgepole pine grown and measured with different inorganic
      nitrogen sources.
AB  - Significant spatial variability in NH4+, NO3- and H+ net fluxes was measured in
      roots of young seedlings of Douglas-fir (Pseudotsuga menziesii) and lodgepole
      pine (Pinus contorta) with ion-selective microelectrodes. Seedlings were grown
      with NH4+, NO3-, NH4NO3 or no nitrogen (N), and were measured in solutions
      containing one or both N ions, or no N in a full factorial design. Net NO3- and
      NH4+ uptake and H+ efflux were greater in Douglas-fir than lodgepole pine and in
      roots not exposed to N in pretreatment. In general, the rates of net NH4+ uptake
      were the same in the presence or absence of NO3-, and vice versa. The highest NO3
      influx occurred 0-30 mm from the root apex in Douglas-fir and 0-10 mm from the
      apex in lodgepole pine. Net NH4+ flux was zero or negative (efflux) at Douglas
      fir root tips, and the highest NH4+ influx occurred 5-20 mm from the root tip.
      Lodgepole pine had some NH4+ influx at the root tips, and the maximum net uptake
      5 mm from the root tip. Net H+ efflux was greatest in the first 10 mm of roots of
      both species. This study demonstrates that nutrient uptake by conifer roots can
      vary significantly across different regions of the root, and indicates that ion
      flux profiles along the roots may be influenced by rates of root growth and
      maturation.

PMID- 18034774
TI  - Membrane targeting by APPL1 and APPL2: dynamic scaffolds that oligomerize and
      bind phosphoinositides.
AB  - Human adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper
      containing 1 (APPL1) and adaptor protein, phosphotyrosine interaction, PH domain
      and leucine zipper containing 2 (APPL2) are homologous effectors of the small
      guanosine triphosphatase RAB5 that interact with a diverse set of receptors and
      signaling proteins and are proposed to function in endosome-mediated signaling.
      Herein, we investigated the membrane-targeting properties of the APPL1 and APPL2
      Bin/Amphiphysin/Rvs (BAR), pleckstrin homology (PH) and phosphotyrosine binding
      (PTB) domains. Coimmunoprecipitation and yeast two-hybrid studies demonstrated
      that full-length APPL proteins formed homooligomers and heterooligomers and that
      the APPL minimal BAR domains were necessary and sufficient for mediating APPL
      APPL interactions. When fused to a fluorescent protein and overexpressed, all
      three domains (minimal BAR, PH and PTB) were targeted to cell membranes.
      Furthermore, full-length APPL proteins bound to phosphoinositides, and the APPL
      isolated PH or PTB domains were sufficient for in vitro phosphoinositide binding.
      Live cell imaging showed that full-length APPL-yellow fluorescent protein (YFP)
      fusion proteins associated with cytosolic membrane structures that underwent
      movement, fusion and fission events. Overexpression of full-length APPL-YFP
      fusion proteins was sufficient to recruit endogenous RAB5 to enlarged APPL
      associated membrane structures, although APPL1 was not necessary for RAB5
      membrane targeting. Taken together, our findings suggest a role for APPL proteins
      as dynamic scaffolds that modulate RAB5-associated signaling endosomal membranes
      by their ability to undergo domain-mediated oligomerization, membrane targeting
      and phosphoinositide binding.

PMID- 18034775
TI  - Ligand binding induces Cbl-dependent EphB1 receptor degradation through the
      lysosomal pathway.
AB  - Eph receptor tyrosine kinases play a critical role in embryonic patterning and
      angiogenesis. In the adult, they are involved in carcinogenesis and pathological
      neovascularization. However, the mechanisms underlying their role in tumor
      formation and metastasis remain to be defined. Here, we demonstrated that
      stimulation of EphB1 with ephrinB1/Fc led to a marked downregulation of EphB1
      protein, a process blocked by the lysosomal inhibitor bafilomycin. Following
      ephrinB1 stimulation, the ubiquitin ligase Cbl was recruited by EphB1 and then
      phosphorylated. Both Cbl phosphorylation and EphB1 ubiquitination were blocked by
      the Src inhibitor PP2. Overexpression of wild-type Cbl, but not of 70Z mutant
      lacking ligase activity, enhanced EphB1 ubiquitination and degradation. This
      negative regulation required the tyrosine kinase activity of EphB1 as kinase-dead
      EphB1-K652R was resistant to Cbl. Glutathione S-transferase binding experiments
      showed that Cbl bound to EphB1 through its tyrosine kinase-binding domain. In
      aggregate, we demonstrated that Cbl induces the ubiquitination and lysosomal
      degradation of activated EphB1, a process requiring EphB1 and Src kinase
      activity. To our knowledge, this is the first study dissecting the molecular
      mechanisms leading to EphB1 downregulation, thus paving the way to new means of
      modulating their angiogenic and tumorigenic properties.

PMID- 18034777
TI  - Assessment of the efficacy and safety of intravenous conivaptan in patients with
      euvolaemic hyponatraemia: subgroup analysis of a randomized, controlled study.
AB  - OBJECTIVE AND DESIGN: Most cases of euvolaemic hyponatraemia are associated with
      elevated plasma levels of AVP. Conivaptan is a high-affinity, nonpeptide
      vasopressin V(1A)/V(2)-receptor antagonist. We performed a subgroup analysis of a
      multicentre, randomized, placebo-controlled, double-blind, parallel-group study
      to evaluate the efficacy and safety of intravenous (i.v.) conivaptan for the
      treatment of euvolaemic hyponatraemia. PATIENTS: Fifty-six euvolaemic patients
      with serum [Na(+)] of 115 to < 130 mmol/l received conivaptan 40 or 80 mg/day or
      placebo via continuous i.v. infusion for 4 days. A 20-mg loading dose was
      administered intravenously over 30 min in the conivaptan groups; the placebo
      group received a placebo loading dose. MEASUREMENTS: Change in serum [Na(+)],
      measured by the baseline-adjusted area under the serum [Na(+)]-time curve (AUC),
      was the primary efficacy parameter. Secondary efficacy measures included the time
      from the first dose to a confirmed > or = 4 mmol/l increase in serum [Na(+)],
      total time with serum [Na(+)] > or = 4 mmol/l above baseline, change in serum
      [Na(+)] from baseline, and number of patients with a confirmed > or = 6 mmol/l
      increase in serum [Na(+)] or normal [Na(+)]. Safety assessments included adverse
      events (AE), incidence of overly rapid correction of serum [Na(+)], and changes
      in vital signs and electrocardiographic and clinical laboratory parameters.
      RESULTS: During the first 2 days of treatment, and over the entire 4-day
      treatment period, both conivaptan doses significantly increased the serum [Na(+)]
      AUC more than placebo (P < 0.01). Conivaptan 40 and 80 mg/day significantly
      improved all secondary efficacy measures. Conivaptan was generally well
      tolerated; infusion-site reaction was the most common AE. CONCLUSIONS: In
      hospitalized patients with euvolaemic hyponatraemia, i.v. conivaptan
      significantly increased serum [Na(+)] promptly and was well tolerated.

PMID- 18034776
TI  - HIV-1 replication in dendritic cells occurs through a tetraspanin-containing
      compartment enriched in AP-3.
AB  - Dendritic cells (DC) are crucial components of the early events of HIV infection.
      Dendritic cells capture and internalize HIV at mucosal surfaces and efficiently
      transfer the virus to CD4+ T cells in trans through infectious synapses (trans
      infection pathway). Alternatively, HIV-1 replicates in DC (R5-HIV-1) (cis
      infection pathway). Here, we analyzed HIV trafficking in DC during the trans
      infection pathway as well as the cis-infection pathway. Confocal
      immunofluorescence microscopy demonstrated that after capture by DC, R5-HIV-1 and
      HIV-1 pseudotyped with vesicular stomatitis virus protein G colocalized in a
      viral compartment enriched in tetraspanins including CD81, CD82 and CD9, although
      at different levels, indicating a role of the viral envelope in targeting to the
      tetraspanin-rich compartment. Replication of R5-HIV-1 in DC (cis-infection
      pathway) also led to the accumulation, in an envelope-independent manner, of
      mature viral particles in a tetraspanin-rich compartment. A fraction of the HIV-1
      containing compartments appeared directly accessible from the cell surface. In
      sharp contrast with the trans-infection pathway, the delta-subunit of the adaptor
      protein 3 (AP-3) complex was enriched on the HIV-1-containing compartment during
      R5-HIV-1 replication in DC (cis-infection pathway). Downregulation of AP-3 delta
      adaptin reduced significantly viral particle release from HIV-1-infected DC.
      Together, these studies demonstrate a role for AP-3 in HIV replication in a
      tetraspanin-rich compartment in DC and contribute to the elucidation of the
      trafficking pathways required for DC-T cell transfer of HIV-1 infection, a
      critical step during the early events of HIV infection.

PMID- 18034778
TI  - Sizes of abdominal organs in adults with severe short stature due to severe,
      untreated, congenital GH deficiency caused by a homozygous mutation in the GHRH
      receptor gene.
AB  - OBJECTIVE: To assess the sizes of intra-abdominal organs of adult subjects with
      untreated severe congenital isolated GH deficiency (IGHD) due to lack of
      functional GHRH receptor (GHRH-R), and to verify whether there is proportionality
      between size of organ and adult stature and body surface area (BSA). SUBJECTS AND
      METHODS: By using ultrasound, we studied the sizes (absolute and corrected by
      height, weight and BSA) of the intra-abdominal organs of 18 adult subjects with
      IGHD (eight females, IGHD group) who have never received GH replacement therapy.
      They were all homozygous for the same null mutation (IVS1 + 1G --> A) in the GHRH
      receptor gene (GHRH-R). They were compared with normal controls from the same
      region. RESULTS: After correction for BSA, subjects lacking a functional GHRH-R
      have normal prostate and ovaries size, small spleen and uterus, and large liver,
      pancreas and kidney. CONCLUSIONS: Size of individual abdominal organs is
      influenced in different ways by severe and congenital lack of GH due to a GHRH-R
      mutation.

PMID- 18034779
TI  - Serum levels of the adipokine visfatin are increased in pre-eclampsia.
AB  - OBJECTIVE: Pre-eclampsia (PE) is a serious cardiovascular complication in
      pregnancy which shares risk factors with the metabolic syndrome including insulin
      resistance and obesity. Recently, visfatin was introduced as a novel insulin
      mimetic adipokine which is up-regulated when weight is gained. In the current
      study, we investigated visfatin serum levels in pre-eclamptic patients as
      compared to healthy gestational age-matched controls. PATIENTS AND MEASUREMENTS:
      Visfatin was quantified by ELISA in control (n = 20) and PE (n = 15) patients.
      Furthermore, visfatin was correlated to clinical and biochemical measures of
      renal function, glucose and lipid metabolism, as well as inflammation. RESULTS:
      Mean maternal visfatin serum levels adjusted for maternal age were about twofold
      up-regulated in PE (31.1 +/- 23.4 microg/l) as compared to controls (15.7 +/-
      23.1 microg/l). Furthermore, visfatin concentrations correlated positively with
      age, blood pressure, creatinine, free fatty acids (FFA), IL-6 and C reactive
      protein (CRP), whereas a negative correlation was found with fasting insulin and
      the HOMA-insulin resistance index (HOMA-IR). In multivariate analyses, HOMA-IR
      and CRP remained independently associated with visfatin serum levels and
      explained 58% of the variation in visfatin concentrations. CONCLUSIONS: We show
      that maternal visfatin levels are significantly increased in PE patients.
      Furthermore, insulin sensitivity and inflammatory status independently predict
      serum visfatin levels.

PMID- 18034780
TI  - The evaluation of metabolic parameters and insulin sensitivity for a more robust
      diagnosis of the polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is considered predominantly as a
      hyperandrogenetic syndrome and the evaluation of metabolic parameters and insulin
      sensitivity is not mandatory. CONTEXT: PCOS diagnostic criteria [National
      Institute of Health (NIH), Rotterdam Consensus (ROT), Androgen Excess Society
      (AES)] are unanimous recognized. We aimed to assess in women with suspected PCOS
      whether the application of the three diagnostic criteria differently
      characterizes the metabolic profile and insulin sensitivity. DESIGN:
      Retrospective study in a cohort of women admitted to our Outpatient Clinic for
      suspected PCOS. PATIENTS: Two hundred and four women with suspected PCOS in
      comparison to a group of normal, age-matched Sicilian women (N = 34) without
      signs of metabolic syndrome. MEASUREMENTS: We evaluated hyperandrogenaemia and
      clinical hyperandrogenism, ovarian morphology, hypothalamo-hypophyseal axis and
      metabolic syndrome parameters. An oral glucose tolerance test (OGTT; 75 g
      glucose) measured areas under the curve (AUC) for insulin, C peptide and
      homeostasis model assessment of insulin-resistance (HOMA-IR) were performed.
      RESULTS: The prevalence of PCOS was 51% according to NIH, 83% to ROT and 70.6% to
      AES, and only 100 patients were qualified simultaneously under these three
      criteria. The prevalence of the metabolic syndrome in PCOS women was 26.92%
      (NIH), 21.77% (ROT) and 23.61% (AES), respectively. In comparison to healthy
      women, PCOS women showed increased fasting insulinaemia (PCOS/ROT: P = 0.028;
      PCOS/NIH: P = 0.007; PCOS/EAS: P = 0.023), 120 min insulin after OGTT
      insulinaemia (for the three criteria: P < 0.001), AUC(2h) insulin (for the three
      criteria: P < 0.001) and AUC(2h) C peptide (for the three criteria: P < 0.001).
      CONCLUSIONS: Our study highlights the fact that regardless of the diagnostic
      criteria used, evaluation of the metabolic parameters and insulin sensitivity is
      important for a correct diagnosis of PCOS and a therapeutic approach.

PMID- 18034781
TI  - Multiple biochemical similarities between infectious and non-infectious
      aggregates of a prion protein carrying an octapeptide insertion.
AB  - A nine-octapeptide insertion in the prion protein (PrP) gene is associated with
      an inherited form of human prion disease. Transgenic (Tg) mice that express the
      mouse homolog of this mutation (designated PG14) spontaneously accumulate in
      their brains an insoluble and weakly protease-resistant form of the mutant
      protein. This form (designated PG14(Spon)) is highly neurotoxic, but is not
      infectious in animal bioassays. In contrast, when Tg(PG14) mice are inoculated
      with the Rocky Mountain Laboratory (RML) strain of prions, they accumulate a
      different form of PG14 PrP (designated PG14(RML)) that is highly protease
      resistant and infectious in animal transmission experiments. We have been
      interested in characterizing the molecular properties of PG14(Spon) and
      PG14(RML), with a view to identifying features that determine two, apparently
      distinct properties of PrP aggregates: their infectivity and their pathogenicity.
      In this paper, we have subjected PG14(Spon) and PG14(RML) to a panel of assays
      commonly used to distinguish infectious PrP (PrP(Sc)) from cellular PrP (PrP(C)),
      including immobilized metal affinity chromatography, precipitation with sodium
      phosphotungstate, and immunoprecipitation with PrP(C)- and PrP(Sc)-specific
      antibodies. Surprisingly, we found that aggregates of PG14(Spon) and PG14(RML)
      behave identically to each other, and to authentic PrP(Sc), in each of these
      biochemical assays. PG14(Spon) however, in contrast to PG14(RML) and PrP(Sc), was
      unable to seed the misfolding of PrP(C) in an in vitro protein misfolding cyclic
      amplification reaction. Collectively, these results suggest that infectious and
      non-infectious aggregates of PrP share common structural features accounting for
      their toxicity, and that self-propagation of PrP involves more subtle molecular
      differences.

PMID- 18034782
TI  - Hemodialysis grafts: on the controversial decision to stent venous anastomotic
      stenoses.

PMID- 18034783
TI  - Role of surgical intervention for cephalic arch stenosis in the "fistula first"
      era.
AB  - Cephalic arch stenosis (CAS) is a frequent cause of vascular access dysfunction
      in patients with brachiocephalic fistulae. While percutaneous balloon angioplasty
      has been used to treat CAS, the results of this approach have been poor due to
      multiple factors including resistant nature of the stenosis, development of early
      restenosis, as well as poor patency and high vein rupture rates. In this
      analysis, we report the results of an alternative approach to manage this
      problem. Thirteen patients with frequently recurring CAS were referred for
      surgical intervention. Angiographic images recorded during the prior percutaneous
      procedures were made available to the surgeons. The surgical procedure entailed
      transecting the healthy portion of the cephalic vein distal to the stenotic
      segment in the arch, transposing and anastomosing it to the upper
      basilic/axillary vein. Following surgical revision, development of access
      dysfunction was treated with percutaneous balloon angioplasty. Patency rates for
      angioplasty before and after the surgical revision were evaluated. Primary
      patency rates for angioplasty before the surgical revision were 23%, 8% and 0% at
      3, 6, and 12 months, respectively. Following surgical revision, all patients
      needed angioplasty procedure. However, primary patency increased to 92%, 69%, and
      39% at 3, 6, and 12 months, respectively (p = 0.0001). Secondary patency before
      the surgical revision at 3, 6, and 12 months was 100%, 39%, and 8%, respectively,
      compared with 92% at 3, 6, and 12 months postsurgical revision (p = 0.0003). The
      results of this study demonstrate that surgical transposition of the cephalic
      vein in frequently recurring CAS is a viable option and yields better patency
      rates for future angioplasty procedures.

PMID- 18034784
TI  - Cephalic arch stenosis.
AB  - The Kidney Dialysis Outcomes Quality Initiative guidelines and the Fistula First
      Initiative for vascular access have had a measurable impact on the incidence and
      prevalence of the type of access used to deliver hemodialysis in the United
      States. There has been a yearly increase in the placement of arteriovenous
      fistulas and an exponential increase in endovascular treatment of failing and
      immature fistulas. Undoubtedly, the predominant cause of fistula malfunction is
      stenosis within the access system. The stenotic lesions can occur anywhere within
      the access system from the arteries to the outflow and central veins. One of the
      relatively common sites for stenosis in patients with brachiocephalic fistulas is
      the cephalic arch region. While access stenoses at many other sites have been
      successfully treated with percutaneous balloon angioplasty, the results of this
      approach in the management of cephalic arch stenosis (CAS) have been rather
      disappointing. This has been in part due to multiple factors including the
      resistant nature of the stenosis, the development of early restenosis, as well as
      poor patency and high vein rupture rates. This article discusses the anatomy,
      postulated etiology and percutaneous interventions for the treatment of CAS. In
      addition, the report highlights surgical alternatives to the management of
      stenosis in this segment of the cephalic vein.

PMID- 18034785
TI  - Native arteriovenous fistulas: correlation of intra-access blood flow with
      characteristics of stenoses found during diagnostic angiography.
AB  - Surveillance of the intra-access blood flow (Qa) has improved identification of
      thrombosis risk (Qa < or = 500 ml/minute), and these patients are referred for
      angiogram and angioplasty. The purpose of this study was to correlate the Qa with
      patient and stenotic lesion characteristics both before and after angioplasty in
      a retrospective cohort of 210 patients who were preselected on the basis of
      reduced Qa (369 +/- 121 ml/minute). Angiograms revealed a total of 643 stenoses,
      and all patients had at least one significant stenosis (>50% luminal narrowing).
      There was no significant association between the preangioplasty Qa and the
      number, location, or length of stenoses, but there was a significant negative
      correlation between the degree of stenosis and the preangioplasty Qa. Five
      hundred eighty stenoses in 190 patients were treated with angioplasty; the
      postangioplasty Qa was 633 +/- 208 ml/minute. Of the residual stenoses, all had
      less than 50% narrowing. There was no correlation between the postangioplasty Qa
      and the length or degree of stenoses, but there was a significant negative
      correlation between the postangioplasty Qa and the number of stenoses. We
      conclude that the primary determinant of reduced preangioplasty Qa is the degree
      of stenosis, when stenoses are over 50%, whereas the primary determinant of
      reduced postangioplasty Qa is the number of stenosis. For patients with two or
      more residual stenoses and failure to achieve Qa > 500 p;ml/minute
      postangioplasty, the alternative procedure is a prompt surgical revision in order
      to maintain the goal of access patency.

PMID- 18034786
TI  - In vitro function of buffy coat-derived platelet concentrates stored for 9 days
      in CompoSol, PASII or 100% plasma in three different storage bags.
AB  - BACKGROUND AND OBJECTIVES: The aim of the study was to compare the in vitro
      quality of buffy coat-derived platelet concentrates (PC) during extended storage
      in plasma or additive solution in three different storage bags. MATERIALS AND
      METHODS: A pooled and split design was chosen so that identical PCs were produced
      in either 100% plasma, 70% PASII : 30% plasma or 70% CompoSol : 30% plasma (n = 6
      each). This was repeated for three different manufacturers' platelet storage bags
      (Fresenius, Baxter and Pall). PCs were sampled on days 1, 5, 7 and 9 of storage
      and tested in vitro using a variety of tests of platelet function. For each bag
      type, storage in PASII or Composol was compared with plasma (data taken across
      the entire storage period), and differences occurring with time were analysed for
      all storage media. RESULTS: The pH of all PCs was > 6.8 at day 9 of storage. In
      vitro platelet function, as assessed by markers of platelet activation and
      metabolism, of PCs stored in CompoSol appeared to be similar to that of PCs
      stored in plasma over 9 days of storage. In contrast, PCs stored in PASII tended
      to have significantly higher levels of platelet activation (almost a twofold
      increase in % platelets positive for CD62P by day 5) and lower hypotonic shock
      response (approximately 40%, by day 7) compared to either PCs stored in 100%
      plasma or 70% CompoSol. The magnitude of the differences observed between
      platelet storage media appeared to be dependent on the type of platelet storage
      bag with the highest degree of platelet activation and lowest hypotonic shock
      response values being observed in Fresenius bags in combination with PASII.
      CONCLUSIONS: The maintenance of platelet function in vitro during extended
      storage of PCs in platelet additive solutions is dependent on the combination of
      type of additive solution and type of platelet storage bag. For all bag types
      studied, storage in PASII resulted in poorer platelet function in vitro.

PMID- 18034787
TI  - Modulating the red cell membrane to produce universal/stealth donor red cells
      suitable for transfusion.
AB  - Two approaches have been used to produce universal group O donor red blood cells
      (RBCs) from groups A, B, and AB RBCs. The first involves cleavage of the terminal
      immunodominant sugars from carbohydrate chains on the RBC membrane, using
      specific enzymes, to produce so-called enzyme-converted group O (ECO) RBCs. ECO
      RBCs have been produced from whole units of B RBCs and transfused successfully to
      humans. Group A RBCs (especially A(1) RBCs) have been more difficult. New sources
      of enzymes have produced ECO RBCs from A(1) and A(2) RBCs that do not react with
      powerful monoclonal anti-A. Unfortunately, there are still problems encountered
      with polyclonal human antibodies (i.e. cross-matching). The second approach
      interferes with an antibody reaching its specific antigen on the RBC membrane by
      bonding polyethylene glycol (PEG) to the RBC. PEG will attract water molecules,
      yielding a combination that may block most RBC antigens, including A and B
      antigens. Initial excitement generated by preliminary reports of the possibility
      of producing 'stealth' PEG-RBCs were tempered by the findings of in vitro
      serological problems and possible reduced in vivo RBC survival. Many of these
      problems were solved, but recent findings that PEG is immunogenic in animals and
      humans, and that PEG antibodies can shorten the survival of PEG-RBCs (in rabbits)
      and pegylated proteins (e.g. PEG-asparaginase) in humans, are disturbing,
      suggesting that 'stealth' RBCs may never become a reality.

PMID- 18034788
TI  - In vitro and in vivo effects of potassium and magnesium on storage up to 7 days
      of apheresis platelet concentrates in platelet additive solution.
AB  - BACKGROUND AND OBJECTIVE: Prolonged storage of platelets up to 7 days provides
      improved availability, logistical management and decreased wastage. Beside
      methods of bacterial detection, addition of magnesium and potassium to the
      platelet storage solution (SSP+) may further improve the quality of platelets
      with extended storage. MATERIALS AND METHODS: Apheresis platelets from 10 donors
      were divided and stored in two different platelet additive solutions (PAS)
      (Intersol and SSP+) for a paired comparison. A variety of in vitro platelet
      function and metabolic assays were performed both on day 1 and after 7 days of
      storage. For in vivo study, platelets were labelled with either (111)Indium or
      (51)Chromium after 7 days of storage and were injected into the corresponding
      donor. Serial blood samples were drawn for recovery and survival measurements.
      RESULTS: In vitro parameters for SSP+ showed significantly reduced glycolysis
      (lower glucose consumption and decreased production of lactate), a higher
      hypotonic shock response (HSR) and the extent of shape change reactivity and a
      lower degree of platelet activation by means of RANTES (regulated on activation,
      normal, T cell-expressed, and secreted), CD62p and CD63 expression. Platelet
      recovery on day 7 was higher for Intersol as compared to SSP+, 65 +/- 11 vs. 53
      +/- 13% (P = 0.023), and survival showed no difference 4.2 +/- 1.9 vs. 3.6 +/-
      1.4 days. CONCLUSION: In vitro characteristics of platelets stored in PAS with
      addition of potassium and magnesium indicated higher quality, but this could not
      be verified by the in vivo parameters by means of recovery and survival.

PMID- 18034789
TI  - Molecular network of obesity: what does it promise for pharmacotherapy?
AB  - There is growing evidence that receptors that respond to orexigenic and
      anorexigenic signals of respective neuropeptides are also implicated in
      cognitive, emotional, sensory and motor functions. How do these signals trigger a
      particular appetitive function while also acting in so different contexts in
      controlling non-appetitive behaviours? This perspective seeks an answer in their
      peculiar modular organization when each module planted in complex networks
      controlling appetite is also engaged in different domains. Network analysis may
      be essential in considering pharmacotherapeutic interventions and, in particular,
      when anticipating untoward central effects of agents explored from a therapeutic
      point of view.

PMID- 18034790
TI  - Sibutramine-associated adverse effects: a practical guide for its safe use.
AB  - Obesity is a multifactorial chronic disorder which comprises a serious health
      problem nowadays. The effective management of obesity is difficult in
      contemporary societies where abundance of hypercaloric food and sedentary
      lifestyle is the rule. Apart from lifestyle interventions, which include diet,
      exercise and behavioural treatment, weight-loss medications can also be used for
      the management of obesity. Sibutramine, a selective monoamine reuptake inhibitor,
      is a drug with established efficacy in sustained weight reduction and an overall
      favourable safety profile. However, its action on the sympathetic nervous system
      has linked sibutramine to blood pressure and heart rate elevations. These
      potentially adverse effects as well as other sibutramine-associated side effects
      and their possible underlying mechanisms are reviewed in the present article.
      Compelling evidence from the majority of data in the literature shows that
      sibutramine can be effectively used in conjunction with caloric restriction and
      exercise in obese patients. Hypertension, if adequately treated and frequently
      monitored, is not an absolute contraindication for the prescription of
      sibutramine.

PMID- 18034791
TI  - Duchenne muscle activity evaluation and muscle function preservation: is it
      possible a prophylactic strategy?
AB  - Duchenne muscular dystrophy yields pervasive and progressive muscle mass loss. In
      the current measures relating to the monitoring of disease progression the
      following are relevant (i): the type of scale used, (ii) the clinical
      significance of the attribute being measured and (iii) the mathematical
      properties of the data provided. The high prevalence of obesity at an early stage
      of this pathology could result not only from reduced physical activity, but also
      from low resting energy expenditure, abnormal nutrient utilization or
      overfeeding. This muscle weakness may be attenuated by regular low-intensity
      exercise. However, there is a critical lack of data to support appropriate
      exercise prescription. Because inappropriate activity may exacerbate the
      dystrophic process, a systematic analysis of muscle function to determine
      potential exercise load thresholds to avoid injury in dystrophic mice and dogs,
      and then in humans is recommended.

PMID- 18034792
TI  - Overweight and obesity in Portugal: national prevalence in 2003-2005.
AB  - Obesity is an endemic health problem in most developed countries, requiring
      serious public health attention. The first Portuguese nationwide representative
      survey about obesity (with objective anthropometric measurement) was undertaken
      from 1995 to 1998. This paper presents data coming from the second and most
      recent nationwide representative study of obesity, with objective measurement of
      weight, height, waist and hip circumferences. Data were collected between January
      2003 and January 2005. The survey collected objective body mass index (BMI)
      values of 8116 participants aged 18-64. Main findings were: 2.4% of the sample
      had low weight (BMI < 18.5), 39.4% were overweight (BMI between 25.0 and 29.9),
      and 14.2% obese (BMI > or = 30). Waist circumference measurement showed that
      45.6% of the sample suffers increased cardiovascular health risks associated with
      high waist circumference. The overall overweight/obesity prevalence increased
      from 49.6% (in 1995-1998) to 53.6% (in 2003-2005). These data suggest that
      although obesity was identified as a public health problem one decade ago, action
      to reduce it does not seem to have been very effective to date. Well-defined
      public health intervention must be targeted to specific population groups where
      higher levels of obesity prevalence were found: low socioeconomic level groups
      and low-education level groups.

PMID- 18034793
TI  - Colonosphincteric electromyographic responses to sacral root stimulation:
      evidence for a somatosympathetic reflex.
AB  - The aim of the present study was to determine the effects of selectively
      stimulating the afferent fibres running in the dorsal sacral roots (S1, S2, S3)
      and the somatic (radial and sciatic) nerves on colonic and internal anal
      sphincter (IAS) electromyographic (EMG) activity in anaesthetized cats to try to
      understand how sacral nerve stimulation can improve fecal continence in human.
      Electrically stimulating the afferent fibres present in the sacral dorsal roots
      and somatic nerves inhibited the colonic spike potential frequency (n = 97) and
      increased the slow variations in the sphincteric membrane potential (n = 76).
      These effects were found to have disappeared after administering an alpha
      noradrenergic receptor blocker (n = 64) or sectioning the sympathetic efferent
      fibres innervating these organs (n = 69) suggesting the involvement of the
      sympathetic system in the effects observed. Moreover, no significant differences
      were observed between the effects of sacral dorsal root vs somatic nerve
      stimulation on colonic and sphincteric EMG activity. In conclusion, the data
      obtained here show that neurostimulation applied to the sacral spinal roots may
      improve fecal continence by inhibiting colonic activity and enhancing IAS
      activity via a somatosympathetic reflex.

PMID- 18034794
TI  - DNA sequence heterogeneity in Fim tyrosine-integrase recombinase-binding elements
      and functional motif asymmetries determine the directionality of the fim genetic
      switch in Escherichia coli K-12.
AB  - Phase-variable expression of type 1 fimbriae in Escherichia coli K-12 involves
      inversion by site-specific recombination of a 314 bp sequence containing the
      promoter for fim structural gene expression. The invertible sequence is flanked
      by 9 bp inverted repeats, and each repeat is in turn flanked by non-identical
      recombinase-binding elements (RBEs) to which the FimB or FimE site-specific
      recombinases bind. These proteins have distinct DNA inversion preferences: FimB
      inverts the switch in the ON-to-OFF and OFF-to-ON directions with similar
      efficiencies, whereas FimE inverts it predominantly in the ON-to-OFF direction.
      We have found that FimB and FimE invert the switch through a common mechanism. A
      genetic investigation involving base-by-base substitution combined with a
      biochemical study shows that the same DNA cleavage and religation sites are used
      within the 9 bp inverted repeats, and that each recombination involves a common 3
      bp spacer region. A comprehensive programme of RBE exchanges and replacements
      reveals that FimB is much more tolerant of RBE sequence variation than FimE. The
      asymmetric location of conserved 5'-CA motifs at either side of each spacer
      region allows the inside and outside of the switch to be differentiated while the
      RBE sequence heterogeneity permits its ON and OFF forms to be distinguished by
      the recombinases.

PMID- 18034795
TI  - XthA (Exonuclease III) regulates loading of RecA onto DNA substrates in log phase
      Escherichia coli cells.
AB  - Exonucleases can modify DNA substrates created during DNA replication,
      recombination and repair. In Escherichia coli, the effects of several 3'-5'
      exonucleases on RecA loading were studied by assaying RecA-GFP foci formation.
      Mutations in xthA (ExoIII), xseAB (ExoVII), xni (ExoIX), exoX (ExoX) and tatD
      (ExoXI) increased the number of RecA-GFP foci twofold to threefold in a
      population of log phase cells grown in minimal medium. These increases depend on
      xonA. Epistasis analysis shows that ExoVII, ExoX, ExoIX and ExoXI function in a
      common pathway, distinct from ExoIII (and ExoI is upstream of both pathways). It
      is shown (paradoxically) that in xthA mutants, RecA-GFP loading is predominantly
      RecBCD-dependent and that xthA recB double mutants are viable. Experiments show
      that while log phase xthA cells have twofold more double-stranded breaks (DSBs)
      than wild type, they do not induce the SOS response. The increase in RecA loading
      is independent of the base excision repair (BER) proteins Nth, MutM and Nei. It
      is proposed that log phase cells produce DSBs that do not induce the SOS
      response. Furthermore, ExoI, ExoIII and the other 3'-5' exonucleases process
      these DSBs, antagonizing the RecBCD pathway of RecA loading, thus regulating the
      availability of these substrates for recombination.

PMID- 18034797
TI  - Identifying the factors that determine feedback given to undergraduate medical
      students following formative mini-CEX assessments.
AB  - OBJECTIVE: We aimed to examine the factors that determine provision of feedback
      to students following mini-clinical evaluation exercise (mini-CEX) assessments.
      METHODS: We carried out a pilot study of all final year medical students at the
      University of Aberdeen between November 2005 and June 2006. The study involved
      396 mini-CEX encounters (173 students and 105 assessors). We retrospectively
      analysed the components of feedback recorded on the marking sheets. Each
      component of feedback was coded as a binary response (feedback recorded or not).
      Logistic regression was used to determine the degree and significance of the
      factors that influenced feedback. Specialty block, range of marks, assessor group
      and assessor satisfaction were entered into the analysis using SPSS Version 14.
      RESULTS: The provision of feedback by our assessors was poor. In 22.7% of cases,
      positive features were not identified; in 28.2% of cases, no suggestions for
      development were highlighted; in 49.7% of cases, no action plan was formulated.
      Assessors who gave a wider range of scores for the specific skill domains were
      more likely to record areas for development and action plans. Specialty block
      influenced feedback on areas for development. Suggesting an action plan was
      significantly associated with assessor group, and academic trainees were the most
      consistent providers of feedback. Assessor satisfaction was significantly
      associated with highlighting 'anything especially good'. CONCLUSIONS: Numerous
      factors were associated with the provision of feedback in our cohort. Assessor
      training may address this variability. However, this would limit the diversity of
      assessors, which may be undesirable. More research is required on assessor
      training and recruitment.

PMID- 18034796
TI  - Mutation of a single residue, beta-glutamate-20, alters protein-lipid
      interactions of light harvesting complex II.
AB  - It is well established that assembly of the peripheral antenna complex, LH2, is
      required for proper photosynthetic membrane biogenesis in the purple bacterium
      Rhodobacter sphaeroides. The underlying interactions are, as yet, not understood.
      Here we examined the relationship between the morphology of the photosynthetic
      membrane and the lipid-protein interactions at the LH2-lipid interface. The non
      bilayer lipid, phosphatidylethanolamine, is shown to be highly enriched in the
      boundary lipid phase of LH2. Sequence alignments indicate a putative lipid
      binding site, which includes beta-glutamate-20 and the adjacent carotenoid end
      group. Replacement of beta-glutamate-20 with alanine results in significant
      reduction of phosphatidylethanolamine and concomitant raise in
      phosphatidylcholine in the boundary lipid phase of LH2 without altering the lipid
      composition of the bulk phase. The morphology of the LH2 housing membrane is,
      however, unaffected by the amino acid replacement. In contrast, simultaneous
      modification of glutamate-20 and exchange of the carotenoid sphaeroidenone with
      neurosporene results in significant enlargement of the vesicular membrane
      invaginations. These findings suggest that the LH2 complex, specifically beta
      glutamate-20 and the carotenoids' polar head group, contribute to the shaping of
      the photosynthetic membrane by specific interactions with surrounding lipid
      molecules.

PMID- 18034798
TI  - Making a difference: researching master's and doctoral research programmes in
      medical education.
AB  - CONTEXT: The Association for the Study of Medical Education states that its aim
      is to improve the quality of medical education. As a consequence, it commissioned
      through its Education Research Group a small-scale project to explore the quality
      of the research methods elements in currently available UK master's and doctoral
      programmes. OBJECTIVE: This study aimed to explore the breadth, depth and
      diversity of the research methods provision of those programmes currently
      available to course participants. METHODS: The study comprised a 3-phase approach
      which utilised: a web-based search of curricula format and content; semi
      structured interviews with key informants, and case studies and site visits to
      conduct documentary analysis of dissertations and in-depth interviews with core
      personnel. RESULTS: The study revealed wide variation across taught programmes.
      These discrepancies applied to length of course, requirements for the
      dissertation in terms of both length and time allowed to complete the study and,
      crucially, a wide variance in the quality and quantity of the levels of
      supervision provided for students during this research phase. DISCUSSION: This
      study raises concerns about the aims and functions of courses offering
      qualifications in medical education. It identifies a number of obstacles to the
      development of educational researchers who are skilled in the philosophical
      underpinnings of research activity or equipped to undertake educational research
      that is of a quality sufficient to withstand the scrutiny of the authors'
      scientific and clinical counterparts. We argue that if research into medical
      education is to thrive, it requires the full commitment of all those who are
      engaged in teaching the topic and supporting researchers.

PMID- 18034799
TI  - Medical education: it's time for a transatlantic dialogue.

PMID- 18034800
TI  - Speciation reversal and biodiversity dynamics with hybridization in changing
      environments.
AB  - A considerable fraction of the world's biodiversity is of recent evolutionary
      origin and has evolved as a by-product of, and is maintained by, divergent
      adaptation in heterogeneous environments. Conservationists have paid attention to
      genetic homogenization caused by human-induced translocations (e.g. biological
      invasions and stocking), and to the importance of environmental heterogeneity for
      the ecological coexistence of species. However, far less attention has been paid
      to the consequences of loss of environmental heterogeneity to the genetic
      coexistence of sympatric species. Our review of empirical observations and our
      theoretical considerations on the causes and consequences of interspecific
      hybridization suggest that a loss of environmental heterogeneity causes a loss of
      biodiversity through increased genetic admixture, effectively reversing
      speciation. Loss of heterogeneity relaxes divergent selection and removes
      ecological barriers to gene flow between divergently adapted species, promoting
      interspecific introgressive hybridization. Since heterogeneity of natural
      environments is rapidly deteriorating in most biomes, the evolutionary ecology of
      speciation reversal ought to be fully integrated into conservation biology.

PMID- 18034801
TI  - Hormones and honest signals: males with larger ornaments elevate testosterone
      more when challenged.
AB  - When male investment in mating varies with quality, reliable sexual signals may
      evolve. In many songbirds, testosterone mediates mating investment, suggesting
      that signals should be linked to testosterone production. However, because
      testosterone may change rapidly during behaviour such as territorial aggression
      and courtship, efforts to establish such a relationship have proved challenging.
      In a population of dark-eyed juncos, we measured individual variation in the
      production of short-term testosterone increases by injecting gonadotropin
      releasing hormone (GnRH). We found a positive correlation between the magnitude
      of these increases and the size of a plumage ornament ('tail white') previously
      shown to be important for female choice and male-male competition. We then
      measured naturally elevated testosterone levels produced during male-male
      competition and found that they covaried with those induced by GnRH. We suggest
      that the association between tail white and testosterone increases may allow
      conspecifics to assess potential mates and competitors reliably using tail white.

PMID- 18034802
TI  - Sexual size dimorphism predicts the frequency of multiple mating in the sex-role
      reversed pipefish Syngnathus typhle.
AB  - The sex-role reversed pipefish Syngnathus typhle is a member of the Syngnathidae,
      a family of fishes in which males brood embryos on their body surface. As in most
      ectotherms, embryonic development is highly temperature dependent in syngnathids
      and male brooding periods are extended when water temperatures are reduced. The
      influence of temperature on reproduction is expected to effectively truncate the
      breeding season and reduce fecundity in cold waters, potentially enhancing the
      opportunity for both fecundity and sexual selection. We studied spatial variation
      in the morphology and reproductive biology of S. typhle in five European
      populations which vary in latitude and water temperature. Microsatellite analyses
      indicated that the average number of male mates per population ranged between 1.3
      and 3.7. The frequency of multiple mating by males was negatively correlated with
      the degree of sexual size dimorphism in each population, suggesting that
      disproportionate increases in female fecundity may be able to compensate for
      increased male brood pouch capacity. Both sexes were larger and males had an
      increased brood size where water temperatures during the breeding season were
      lower. Morphological variation among populations may be mediated by differences
      in fecundity selection associated with different optimal reproductive strategies
      in cold and warm water environments.

PMID- 18034803
TI  - Coevolution and the adaptive value of autumn tree colours: colour preference and
      growth rates of a southern beech aphid.
AB  - The evolutionary explanation for the change in leaf colour during autumn is still
      debated. Autumn colours could be a signal of defensive commitment towards insects
      (coevolution) or an adaptation against physical damage because of light at low
      temperatures (photoprotection). These two hypotheses have different predictions:
      (1) under the coevolution hypothesis, insects should not prefer red leaves in
      autumn and grow better in spring on trees with green autumn leaves; and (2) under
      the photoprotection hypothesis, insects should prefer and grow better on trees
      with red leaves because they provide better nutrition. Studying colour preference
      in autumn and growth rates in spring of a southern beech aphid species
      (Neuquenaphis staryi) on Nothofagus alessandrii, we found preference for green
      leaves in autumn but no differential performance of aphids in spring. We suggest
      that aphid preference for green might have evolved to exploit better their host
      during the autumn rather than to improve their performance in spring.

PMID- 18034804
TI  - Heritability, plasticity and canalization of Ural owl egg size in a cyclic
      environment.
AB  - Avian egg size is highly variable on the population level, but is considered
      inflexible on the individual level. On the basis of 2969 measurements of
      individual eggs collected during 1981-2005, we analysed heritability, plasticity
      and selection on egg size in the Ural owl, a long-lived bird that preys on voles.
      Vole abundance varied in a 3-year cycle, creating varying food supply across the
      cycle's phases. Ural owl egg size is heritable (h(2) = 60%). Ural owls lay larger
      eggs in improved food conditions. On the basis of repeated breeding records of 59
      females that bred in all vole cycle phases, we show that intra-individual
      adjustment (plasticity) explained 22.4% of the variation in egg size across
      phases. Egg size was under stabilizing selection. Extremely small and extremely
      large eggs had reduced hatchability, and individuals who laid either large or
      small eggs had lower lifetime fledgling production than the ones laying
      intermediately sized eggs. Our findings illustrate how maternal investment in egg
      size can both be heritable and highly responsive to variable environmental
      conditions, and suggest that variation in the investment in egg size across
      individuals is canalized.

PMID- 18034805
TI  - Testing for evolutionary trade-offs in a phylogenetic context: ecological
      diversification and evolution of locomotor performance in emydid turtles.
AB  - The evolution of ecological trade-offs is an important component of ecological
      specialization and adaptive radiation. However, the pattern that would show that
      evolutionary trade-offs have occurred between traits among species has not been
      clearly defined. In this paper, we propose a phylogeny-based definition of an
      evolutionary trade-off, and apply it to an analysis of the evolution of trade
      offs in locomotor performance in emydid turtles. We quantified aquatic and
      terrestrial speed and endurance for up to 16 species, including aquatic, semi
      terrestrial and terrestrial emydids. Emydid phylogeny was reconstructed from
      morphological characters and nuclear and mitochondrial DNA sequences.
      Surprisingly, we find that there have been no trade-offs in aquatic and
      terrestrial speed among species. Instead, specialization to aquatic and
      terrestrial habitats seems to have involved trade-offs in speed and endurance.
      Given that trade-offs between speed and endurance may be widespread, they may
      underlie specialization to different habitats in many other groups.

PMID- 18034806
TI  - Genetic basis of adaptive evolution of a polyphenism by genetic accommodation.
AB  - Polyphenisms are evolved adaptations in which a genome produces discrete
      alternative phenotypes in different environments. In this study, the genetic
      basis of the evolution of a polyphenism by genetic accommodation was
      investigated. A polyphenic strain and a monophenic strain of Manduca sexta (L.)
      were crossed and the F(1) offspring and backcross progeny were analysed. The
      larval colour polyphenism was found to be regulated by one sex-linked gene of
      major effect and many smaller effect modifier genes. The finding shows that the
      mechanism of genetic accommodation relies on genetic changes that are consistent
      with the current view of the genetic basis of adaptive evolution.

PMID- 18034807
TI  - Environmental stress and the costs of whole-organism phenotypic plasticity in
      tadpoles.
AB  - Costs of phenotypic plasticity are important for the evolution of plasticity
      because they prevent organisms from shaping themselves at will to match
      heterogeneous environments. These costs occur when plastic genotypes have
      relatively low fitness regardless of the trait value expressed. We report two
      experiments in which we measured selection on predator-induced plasticity in the
      behaviour and external morphology of frog tadpoles (Rana temporaria). We assessed
      costs under stressful and benign conditions, measured fitness as larval growth
      rate or competitive ability and focused analysis on aggregate measures of whole
      organism plasticity. There was little convincing evidence for a cost of
      phenotypic plasticity in our experiments, and costs of canalization were nearly
      as frequent as costs of plasticity. Neither the magnitude of the cost nor the
      variation around the estimate (detectability) was sensitive to environmental
      stress.

PMID- 18034808
TI  - Female coloration indicates female reproductive capacity in blue tits.
AB  - It is poorly understood whether female morphological and behavioural traits can
      be used as 'signals'. In particular, experimental tests of the hypothesis that
      female ornaments reflect quality are scarce. Here, we experimentally examine
      whether female plumage coloration might signal maternal quality in the blue tit,
      Cyanistes caeruleus by forcing half of the females breeding in our population to
      produce a replacement clutch. Using statistical models that controlled for the
      effects of male coloration, and the effects of age and condition of both parents,
      we found that carotenoid-based female coloration was positively linked to key
      proxies of bird lifetime reproductive success: clutch size, fledgling success and
      recruitment. Importantly, the relationships between maternal yellow carotenoid
      coloration and both clutch size and recruitment were stronger in the experimental
      group than in the control group, indicating that breeding females with higher
      values of yellow coloration were better able to handle the cost of producing a
      second clutch. Finally, UV-blue female coloration was positively linked to female
      survival and marginally linked to laying date. Taken together, these results show
      for the first time in a natural population that female coloration can indicate
      individual and maternal quality under natural and adverse reproductive
      conditions. They highlight the potential for the evolution of female ornamental
      traits through sexual selection.

PMID- 18034809
TI  - Significant effect of hepatitis C virus specific CTLs on viral clearance in
      patients with type C chronic hepatitis treated with antiviral agents.
AB  - AIM: To evaluate the correlation between hepatitis C virus (HCV) specific
      cytotoxic T lymphocytes (CTLs) and viral clearance in antiviral treated patients,
      we examined the number and function of HCV epitope-specific CTLs and the viral
      load in 12 HLA-A2-positive patients with chronic hepatitis C, after undergoing
      interferon therapy. METHODS: Peripheral blood mononuclear cells (PBMC) were
      analyzed on days 0, 3, 7, 14 and 28 of undergoing antiviral therapies. To
      investigate the quantity of the antigen specific CTLs, CD8-positive T cells were
      isolated using microbeads and were stained for HLA-A*0201 tetramers. To
      investigate the function of CTLs, PBMC were stimulated with the same synthetic
      epitope peptides and analyzed to determine their interferon (IFN)-gamma
      expression. RESULTS: In seven patients, HCV-RNA became undetectable 4 weeks after
      antiviral therapies (EVR), but five patients were non-responders (NR). In peptide
      NS3 1406 on day 3 and day 7 of therapy and in NS3 1073 on day 3 of therapy, the
      level of IFN-gamma expression on CD8+ T cells was significantly higher in the EVR
      group than in the NR group. In other peptides, the number of and cytokine
      production from the CTLs in the EVR group were also higher than in the NR group,
      but not significantly. CONCLUSION: After antiviral therapy, analysis of the
      number and function of antigen-specific CTLs in the early phase was thus found to
      be useful for predicting viral clearance in chronic hepatitis C patients.

PMID- 18034810
TI  - Partial splenic embolization.
AB  - Partial splenic embolization (PSE) is a non-surgical procedure developed to treat
      hypersplenism as a result of hepatic disease and thus avoid the disadvantages of
      splenectomy. A femoral artery approach is used for selective catheterization of
      the splenic artery. Generally, the catheter tip is placed as distally as possible
      in an intrasplenic artery. After an injection of antibiotics and steroids,
      embolization is achieved by injecting 2-mm gelatin sponge cubes suspended in a
      saline solution containing antibiotics. PSE can benefit patients with
      thrombocytopenia, esophagogastric varices, portal hypertensive gastropathy,
      encephalopathy, liver dysfunction, splenic aneurysm, and splenic trauma. The
      contraindications of PSE include secondary splenomegaly and hypersplenism in
      patients with terminal-stage underlying disease; pyrexia or severe infections are
      associated with a high risk of splenic abscess after PSE. Complications of PSE
      include daily intermittent fever, abdominal pain, nausea and vomiting, abdominal
      fullness, appetite loss, and postembolization syndrome. Decreased portal-vein
      flow and a rapid increase in the platelet count after excessive embolization may
      cause portal-vein or splenic-vein thrombosis.

PMID- 18034811
TI  - Verbal abuse experienced by nursing students.
AB  - AIM: This paper is a report of a study to describe the nature, severity,
      frequency and sources of verbal abuse experienced by nursing students while
      gaining clinical experience. BACKGROUND: Verbal abuse of healthcare workers is
      currently receiving considerable attention and nursing students have been
      identified as a group vulnerable to experiencing workplace verbal abuse. METHOD:
      Questionnaires were distributed in 2005 to a convenience sample of 156 third year
      nursing students from one pre-registration nursing programme in England. A total
      of 114 questionnaires were returned, giving a response rate of 73.0%. FINDINGS:
      Experience of verbal abuse was reported by 45.1% of respondents, 34.5% had
      witnessed other students experiencing this and 65.5% reported that they were
      aware of other students experiencing verbal abuse. The incidents involved
      patients in 64.7% of cases, 15.7% involved visitors or relatives and 19.6%
      involved other healthcare workers. Students reported experiencing threats to kill
      them, racial abuse and sexually oriented verbal abuse, with the majority of
      incidents occurring in general medical, mental health and general surgical
      clinical areas. CONCLUSION: Education and healthcare providers should prepare
      students to manage negative verbal exchanges during nursing education, and
      policies and support networks relating to managing verbal abuse in clinical
      practice should be available to nursing students.

PMID- 18034812
TI  - School nurses and sex education: surveillance and disciplinary practices in
      primary schools.
AB  - AIM: This paper is a report of a study to explore how school nurses perceive the
      influence of schools on their role in delivering sex and relationship education
      in primary schools. BACKGROUND: School nurses play a key role in sex education in
      English schools. However, sex education is a contentious issue meaning the sex
      education of children is often an area of tension within the curriculum. However,
      the impact of these tensions upon school nursing practice is poorly described.
      METHOD: Three focus groups with a convenience sample of 16 nurses experienced in
      conducting sex and relationship education were conducted during 2006. Focus
      groups were audio-taped, transcribed verbatim and subjected to a thematic
      analysis. FINDINGS: Four themes were identified in the data: 'covert
      surveillance' refers to school staff conducting clandestine surveillance of the
      classroom actions of the nurse; 'overt surveillance' reflects how nurses felt
      they were being openly monitored by teachers in the classroom; 'Teacher attitude'
      refers to the interventions of the supervising teacher in the classroom during
      the sex education session and 'resistance practices' detailed how nurses
      attempted to manage the disciplinary practices of the school. CONCLUSION: School
      nurses need to be pragmatic about the fact that there will be some attempts by
      the school to regulate sex education. Developing an early dialogue with the
      school can mediate this. Closer working practices and the involvement of school
      nurses in the development of sex education policy and practice is vital to ensure
      that they continue to make a valuable contribution to sex education in schools.

PMID- 18034813
TI  - Burnout and its correlates among nursing staff: questionnaire survey.
AB  - AIM: This paper is a report of a study to determine the burnout level and its
      correlates in nurses. BACKGROUND: Healthcare providers and especially nurses are
      generally considered a high risk group regarding work stress and burnout and this
      syndrome has been a major concern in the field of occupational health. METHOD:
      The study was carried out at a university hospital in Turkey during May-June
      2005. A total of 418 nurses from the 474 working at the hospital at the time
      (88.2%) answered a self-administered questionnaire including the Maslach Burnout
      Inventory. FINDINGS: All the nurses were female, with a mean age of 30.6 (5.4)
      and a median age of 29 years. The mean score was 17.99(6.35) for the Emotional
      Exhaustion subscale, 5.72 (3.87) for the Depersonalization subscale and 19.83
      (4.66) for the Personal Accomplishment subscale. Emotional Exhaustion decreased
      with increasing age (P < 0.05). Total time in the job, weekly working hours,
      shift-working and the unit where employed influenced burnout scores (P < 0.05).
      Not being happy with relations with superiors, not finding the job suitable,
      feeling anxious about the future, perceived poor health, problems with personal
      life and financial difficulties were also factors influencing burnout scale
      scores (P < 0.05). CONCLUSION: It is necessary to consider nurses having the
      characteristics shown as the correlates of burnout in this study as a target
      group, to screen periodically the burnout status and improve their working
      conditions, especially relationships with colleagues.

PMID- 18034814
TI  - Lifestyle limitations of children and young people with severe cerebral palsy: a
      population study protocol.
AB  - AIM: This paper is a presentation of a study protocol to establish the prevalence
      of orthopaedic problems (hip dislocation, pelvic obliquity, spinal deformity and
      contractures) and their impact on pain, function, participation and health in a
      population of children and young people with severe cerebral palsy. BACKGROUND:
      Cerebral palsy is the commonest cause of motor impairment in childhood and is
      associated with life-long disability. An estimated 30% of people with cerebral
      palsy have severe forms and are non-ambulant. Although the underlying
      neurological damage is not amenable to correction, many health services are
      dedicated to providing therapeutic and adaptive support to help people with the
      condition reach their potential. METHOD: A cross-sectional survey of children and
      young people, aged 4-25 years with severe, non-ambulant cerebral palsy as defined
      using the Gross Motor Function Classification System (Levels IV and V). Study
      participants will be identified from a pre-existing, geographically defined case
      register and recruited via a healthcare professional known to them. Two
      assessments will be undertaken: one involving parents/carers at home and using
      questionnaires; the other involving the child/young person ideally in one of
      three settings and including X-rays if clinically indicated. DISCUSSION: This
      study will contribute to our knowledge of the history and epidemiology of
      orthopaedic problems in children and young people with cerebral palsy and how
      these problems accumulate and impact on participation, health and well-being. The
      study will also identify unmet need and make recommendations for good practice in
      relation to the orthopaedic care and management for people with severe cerebral
      palsy.

PMID- 18034815
TI  - Warrior nurse: duality and complementarity of role in the operational
      environment.
AB  - AIM: This paper is a report of a study to explore the nature of military nursing
      in an environment of war, in particular the union of personal, professional and
      organizational tenets and to identify the actual or potential effect this had on
      the nursing role in this unique environment. BACKGROUND: The history of nursing
      is intrinsically linked with war. There is an irony to this relationship. Active
      involvement with military activities has provided a vehicle in which nursing has
      developed, albeit through fostering war, which itself destroys health and
      contravenes the ethos of nursing. Military nurses, one would assume, are able to
      reconcile the dichotomy existing between their caring role and being a member of
      an organization associated with conflict. METHODS: A grounded theory design was
      adopted and the data were collected from 1999 to 2002 using a series of in-depth
      interviews and focus group with of 24 military nurses. FINDINGS: Three categories
      were identified: 'It's Just Different Levels', 'That Double Hat' and 'It's Who We
      Are!' The first illustrates the reality of conflict. 'That Double Hat' outlines
      the military nurses dual role: those of caring and the military. 'It's Who We
      Are!' demonstrates the transition from nurse-to-warrior. These integrate to
      create the core category: 'Caring for War: Transition to Warrior'. CONCLUSION:
      The symbiotic relationship of carer and warrior arises as a consequence of
      strategies used by military nurses to embrace their dual role. Further research
      is needed to explore the essence of the caring role within a conflict zone from
      military and civilian perspectives.

PMID- 18034816
TI  - Cue-responding behaviours of oncology nurses in video-simulated interviews.
AB  - AIM: This paper is a report of a study to describe nurse-patient interactions,
      i.e. nurses' cue-responding behaviour in encounters with actors playing the role
      of patients. BACKGROUND: Patients with cancer seldom express their concerns
      directly but express cues instead. Few studies empirically investigated nurses'
      cue-responding behaviour and the subsequent influence of disclosure of cues and
      concerns. METHODS: In this descriptive observational study, conducted from April
      to June 2004, five oncology nurses interviewed an actor playing the role of a
      patient with cancer. Each nurse performed seven different interviews (n = 35);
      these were videotaped and subsequently rated for cue-responding using the Medical
      Interview Aural Rating Scale. Mixed model analysis was used to investigate the
      relation between cues and cue-responding. FINDINGS: Half of the patients' cues
      were responded to with distancing behaviours. The other half of the cues were
      either explored (33%) or acknowledged (17%). In 16% of these responses, nurses
      used open directive questions. One out of four open directive questions were used
      as a distancing response, suggesting that open directive questions are not used
      to explore or acknowledge cues of patients. Cue-responding influenced subsequent
      expression of concerns and emotions, i.e. disclosure of a concern is two times
      higher after exploration or acknowledging of a preceding cue than after a
      distancing response. CONCLUSION: Cue-responding is a valuable concept which can
      contribute to our understanding of optimal ways of communicating. Cue-responding
      behaviour facilitates the disclosure of worries and concerns of patients. Further
      research is needed to assess the clinical relevancy of cue-responding.

PMID- 18034817
TI  - Registered Nurses' perceptions of their work and professional development.
AB  - AIM: This paper is a report of a study to elucidate Registered Nurses'
      perceptions of their work and professional development 6 years after graduation.
      BACKGROUND: Nursing education and health care has rapidly changed in the last two
      decades. Education and experience are important components in Registered Nurses'
      ability to promote a high quality of care, but a great deal depends on their work
      circumstances. This study emphasizes Registered Nurses' view of their work in
      health care, at a time in their career when they have several years of
      experience. METHOD: Data were collected in 2003 from in-depth interviews with 15
      Registered Nurses 6 years after their graduation. The interviews were semi
      structured and analysed with interpretive content analysis. FINDINGS: The
      findings revealed two themes and five sub-themes. The first theme, An appropriate
      but demanding profession, consisted of two sub-themes: 'having found one's niche'
      and 'growing old in nursing may be difficult'. The second theme, A profession
      with opportunities and obstacles, consisted of three sub-themes: 'being aware of
      Registered Nurses' potential', 'having knowledge that is seldom made use of' and
      'attaining professional growth is no matter of course'. CONCLUSION: Keeping
      Registered Nurses' satisfied and avoiding their dissatisfaction is crucial for
      both educators and employers. It is essential that employers give priority to
      Registered Nurses' time with patients and to motivate and support them in
      professional development. Further intervention studies regarding a change of the
      balance between obstacles and opportunities are needed.

PMID- 18034818
TI  - An integrated mid-range theory of postpartum family development: a guide for
      research and practice.
AB  - AIM: This paper is a report of a study to identify parents' perceptions of
      postpartum family experiences. BACKGROUND: There is a growing worldwide emphasis
      on family support. Government policy in the United Kingdom advocates a family
      centred approach in which a core universal postbirth service is offered to all
      families with additional support for parents of children with complex needs.
      Health visitors provide family postpartum care without an agreed theory directing
      or standardizing practice. There is a need to identify parental experiences to
      define family-centred care. METHOD: A qualitative, exploratory approach was
      undertaken using a purposive sample of 17 postpartum families. Data were
      collected in one region of Northern Ireland in 2001-2002. Participants'
      experiences and views were accessed during two focus groups with a total of seven
      participants, and six in-depth interviews. Thematic analysis was conducted.
      FINDINGS: One core theme, 'thriving and surviving', and three main themes, 'baby
      nurture', 'life changes', 'coping and adapting resources', were identified to
      describe how parents developed during the first 8-week postpartum. These were
      influenced by the physical, the psychosocial and the environmental factors. The
      identified themes were mapped together to form an Integrated Mid-Range Theory of
      Postpartum Parent Development. CONCLUSION: As parents need to negotiate
      successfully both present coping and future development during the postpartum
      period, there is a need for professionals to offer services that are orientated
      to holistic short- and long-term well-being. The findings, further to additional
      research, may be used by health visitors and other professionals to direct
      universal postpartum care.

PMID- 18034819
TI  - A resource-based perspective on retention strategies for nurse epidemiologists.
AB  - AIM: This paper is a report of a study to evaluate the intent of epidemiologists
      to remain in their chosen career and identify the variables that contributed to
      or predicted their intent to stay. BACKGROUND: Recently, emerging new infections,
      such as severe acute respiratory syndrome or bird flu, have placed significant
      occupational and psychological stress on epidemiologists, especially in South
      East Asia, resulting in a high intent to change their career. In the light of
      possible staff shortages, retention strategies for epidemiologists have gained
      importance. METHODS: A self-administered questionnaire survey and stratified
      sampling were used to collect data from 351 epidemiologists including nurse
      epidemiologists in Taiwan in 2005; response rate was 70.6%. Correlation analysis
      and hierarchical multiple regression analysis were used to examine relationships
      among occupational stress, psychological stress, human resources and intent to
      stay in their career. RESULTS: Occupational stress, psychological stress and
      human resources had an impact on epidemiologists' intent to stay in their career.
      Results show that the relationship between occupational stress (operation and
      personal safety hazard) and intent to stay could be influenced by organizational
      capital, and the relationship between emotional distress and intent to stay could
      be influenced by a broad spectrum of human resources (organizational, social and
      human capital). CONCLUSION: The severe acute respiratory syndrome epidemic raised
      worldwide attention and challenged epidemiologists' intent to stay. Results
      indicate that human resources play an important role in this issue. Managers
      should enhance human resources in organizations as much as possible to attenuate
      epidemiologists' stress, which may, in turn, strengthen their intent to stay.

PMID- 18034820
TI  - Nurses and Internet health information: a questionnaire survey.
AB  - AIM: This paper is a report of a study to identify the extent of postgraduate
      nursing students' information literacy skills in relation to electronic media and
      health information and barriers to accessing this information. BACKGROUND: The
      Internet is a key source of information for a significant group of patients.
      However, there is evidence of quality issues with some Internet health
      information sites. Nurses need to be aware of the range and quality of online
      health information so as to assist patients and families to locate and evaluate
      relevant and current information. METHOD: A questionnaire designed to collect
      quantitative and qualitative data was posted to a convenience sample of all
      students enrolled in a postgraduate nursing programme in December 2005. The
      response rate was 55.1% or 123 responses. RESULTS: Most respondents had Internet
      access at home and work and believed that access to online health information
      resources had improved their practice. However, some had difficulties in
      accessing computers at work and insufficient time to search for online health
      information. Concern was expressed about the quality of online information, but
      the majority of respondents did not assess patient use. Frequent users of online
      resources were more likely to assess patient use. CONCLUSION: The development of
      nursing competencies in accessing and using online resources is a key precursor
      to supporting patients and families' use of the medium. Access to Internet
      resources at work, along with training and time for searching, is necessary for
      the development of skills enabling effective use of information technology.

PMID- 18034821
TI  - Construction of recombinant Lactobacillus casei efficiently surface displayed and
      secreted porcine parvovirus VP2 protein and comparison of the immune responses
      induced by oral immunization.
AB  - Lactobacillus casei ATCC 393 was selected as a bacterial carrier for the
      development of mucosal vaccine against porcine parvovirus (PPV) infection. The
      PPV major structural polypeptide VP2 was used as the model parvovirus antigen.
      Two inducible expression systems, namely pPG611.1 of the cell-surface expression
      system and pPG612.1 of the secretion expression system based on the xylose operon
      promoter were used to express the VP2 protein. The immunogenicity of recombinant
      strains producing VP2 protein in two cellular locations, cell-surface exposed and
      secreted, was compared to each other by immunizing mice through the intragastric
      administration. The two types of constructs were able to induce strong specific
      immune responses against VP2 via intragastric administration and maximum titres
      of IgA and IgG were attained on days 46 post oral immunization, while the highest
      antibody levels were obtained with the strain producing the VP2 protein in
      extracellular milieu. The induced antibodies demonstrated neutralizing effects on
      PPV infection.

PMID- 18034822
TI  - Tyr346-->Cys mutation results in factor VIII:C assay discrepancy and a normal
      bleeding phenotype - is this mild haemophilia A?
AB  - Patients with mild haemophilia A may have a discrepancy in the factor VIII
      (FVIII) level when measured with a one-stage assay (FVIII:C1) compared with a two
      stage assay (FVIII:C2). This discrepancy usually results in the one-stage level
      being higher than the two-stage level. A F8 mutation resulting in a Tyr346-->Cys
      substitution within the a1 interdomain region has been described which results in
      the converse assay discrepancy. We report four individuals (three families) who
      have this mutation. Mean FVIII:C1 level was 25 IU dL(-1) compared with a mean
      FVIII:C2 level of 63 IU dL(-1). These individuals had presented opportunistically
      and did not have a clinically significant bleeding disorder. The bleeding
      phenotype correlated with the two-stage assay result rather than the one-stage
      result. FVIII replacement therapy does not appear to be required for these
      individuals.

PMID- 18034823
TI  - The impact of haemophilia on the success of total hip arthroplasty.
AB  - We present the results of 34 total hip arthroplasties performed, on haemophiliac
      patients, between 1983 and 2005. The haematological diagnoses and management are
      discussed, emphasizing their impact on keeping complication levels to a minimum.
      The orthopaedic diagnoses and treatment methods are also highlighted, discussing
      the survivorship and reasons for their failures.

PMID- 18034824
TI  - Genetic features of circular bacteriocins produced by Gram-positive bacteria.
AB  - This review highlights the main genetic features of circular bacteriocins, which
      require the co-ordinated expression of several genetic determinants. In general
      terms, it has been demonstrated that the expression of such structural genes must
      be combined with the activity of proteins involved in maturation
      (cleavage/circularization) and secretion outside the cell via different
      transporter systems, as well as multifaceted immunity mechanisms essential to
      ensuring the bacteria's self-protection against such strong inhibitors. Several
      circular antibacterial peptides produced by Gram-positive bacteria have been
      described to date, including enterocin AS-48, from Enterococcus faecalis S-48
      (the first one characterized), gassericin A, from Lactobacillus gasseri LA39, and
      a similar one, reutericin 6, from Lactobacillus reuteri LA6, butyrivibriocin
      AR10, from the ruminal anaerobe Butyrivibrio fibrisolvens AR10, uberolysin, from
      Streptococcus uberis, circularin A, from Clostridium beijerinckii ATCC 25752, and
      subtilosin A, from Bacillus subtilis. We summarize here the progress made in the
      understanding of their principal genetic features over the last few years, during
      which the functional roles of circular proteins with wide biological activity
      have become clearer.

PMID- 18034825
TI  - Ursodeoxycholic acid: Mechanism of action and novel clinical applications.
AB  - Ursodeoxycholic acid (UDCA) is used in the treatment of cholestatic liver
      diseases, gallstone dissolution, and for patients with hepatitis C virus
      infection to ameliorate elevated alanine aminotransferase levels. The efficacy of
      UDCA treatment has been debated and the mechanisms of action in humans have still
      not defined. Suggested mechanisms include the improvement of bile acid transport
      and/or detoxification, cytoprotection, and anti-apoptotic effects. In this
      review, we summarize the proposed molecular mechanisms for the action of UDCA,
      especially in hepatocytes, and also discuss the putative future clinical usage of
      this unique drug.

PMID- 18034826
TI  - Detection of hepatitis C virus natural recombinant RF1_2k/1b strain among
      intravenous drug users in Uzbekistan.
AB  - AIM: A series of recent studies have indicated the presence of natural
      intergenotypic recombinant hepatitis C virus (HCV) strains in distinct parts of
      the world. The majority of the current genotyping methods are based on analysis
      of either 5'UTR, structural (Core/E1/E2) or non-structural (NS5B) genomic regions
      of the virus. METHODS: In the present study, based on both structural and non
      structural regions, we determined the genotype of 55 anti-HCV-positive
      intravenous drug users (IDUs) in Uzbekistan. RESULTS: HCV-3a (67.3%) was the most
      prevalent genotype in this cohort, followed by HCV-1b (27.3%). A discrepancy in
      results was observed between structural and non-structural regions in one case
      (1.8%). Phylogenetically this strain was related to the previously reported
      RF1_2k/1b variant. Based on accumulated sequences, specific primers were designed
      for polymerase chain reaction (PCR) spanning the tentative intergenotypic
      crossover point of RF1_2k/1b. The sensitivity and specificity of the method were
      assessed using generated template clones of HCV-1b, 2a, 2 k and RF1_2k/1b. The
      method was applied to 55 cases in the present study and only one case showed a
      positive result, indicating that in these individuals, the variant is not present
      as a minor quasispecies clone. CONCLUSION: In conclusion, the finding of
      RF1_2k/1b in Central Asia indicates that the variant has wide geographic
      distribution. The PCR-based screening method developed in this study should be
      useful in further epidemiological and clinical studies on the recombination
      phenomenon in HCV.

PMID- 18034827
TI  - Initial viral response is the most powerful predictor of the emergence of YMDD
      mutant virus in chronic hepatitis B patients treated with lamivudine.
AB  - AIM: Lamivudine (LAM) has been widely used to treat chronic hepatitis B (CHB)
      patients, but the emergence of a LAM-resistant virus greatly limits its
      therapeutic efficacy. In this study, we tried to identify factors affecting the
      emergence of a LAM-resistant virus in CHB patients treated with LAM. METHODS: The
      subjects were 190 CHB patients in continuous LAM therapy (139 males, mean age 50
      years, 87 HBeAg-positive). The mean duration of follow-up was 39 months (range 12
      104). The initial viral response (IVR) was defined as HBV DNA < 4.0 logcopies/mL,
      and the initial biochemical response (IBR) as normalization of alanine
      aminotransferase (ALT) (<40 IU/L) at 6 months. RESULTS: IVR was positive in 86%
      of the patients. The cumulative emergence rates of LAM-resistant virus were 10%
      at 1 year, 30% at 2 years and 46% at 3 years. In univariate analysis, factors
      contributing to the emergence of LAM-resistant virus were baseline HBV DNA > 6.5
      logcopies/mL (P = 0.0044), HBeAg-positivity (P = 0.0062), IBR (P = 0.01) and IVR
      (P < 0.0001). The cumulative emergence rates of LAM-resistant virus in IVR
      positive and -negative patients were 4% and 41% at 1 year, and 41% and 79% at 3
      years. In multivariate analysis, only IVR was an independent factor affecting the
      emergence of LAM-resistant virus (P < 0.0001). CONCLUSION: IVR is a useful factor
      for predicting the emergence of LAM-resistant virus in CHB patients treated with
      LAM. For IVR-negative patients, therapeutic options other than LAM monotherapy
      should be used because of the high incidence of the emergence of LAM-resistant
      virus.

PMID- 18034828
TI  - C-Phycocyanin ameliorates 2-acetylaminofluorene induced oxidative stress and MDR1
      expression in the liver of albino mice.
AB  - AIM: To study the effect of C-Phycocyanin (C-PC), a biliprotein isolated from
      Spirulina platensis, on 2-acetylaminofluorene (2-AAF) induced oxidative stress
      and MDR1 expression in the liver of albino mice. METHODS: In the present study,
      albino mice aged 40-60 days were used. The mice were randomly assigned to four
      groups of six animals each. The first group was treated with the vehicle
      (absolute alcohol), the second group was treated with C-PC (50 mg/kg body
      weight), the third group was treated with 2-AAF (25 mg/kg body weight) and the
      fourth group was treated with C-PC (50 mg/kg body weight) and 2-AAF, daily for 3
      days. The mice were sacrificed and the tissues were collected and stored for
      histology and biochemical studies. RESULTS: 2-AAF induced liver tissue damage in
      albino mice. 2-AAF treatment resulted in upregulation of MDR1 expression and
      enhanced the generation of reactive oxygen species (ROS). It also induced
      phosphorylation of Akt and nuclear translocation of NF-kappaB. Co-administration
      of C-PC and 2-AAF inhibited the expression of MDR1 by preventing ROS generation,
      Akt phosphorylation and NF-kappaB nuclear translocation. CONCLUSION: 2-AAF
      induced oxidative stress is reduced by C-PC treatment. C-PC inhibited the 2-AAF
      induced expression of MDR1 by interfering at the level of ROS generation, Akt
      phosphorylation and NF-kappaB translocation. This study reveals the usefulness of
      C-PC in preventing oxidative stress and downregulation of MDR1 induced by
      xenobiotics like 2-AAF.

PMID- 18034829
TI  - Roles of nuclear factor-kappaB in postischemic liver.
AB  - Hepatic ischemia/reperfusion (I/R) results in a chain of events that culminate in
      liver dysfunction and injury. I/R injury is characterized by early oxidant stress
      followed by an intense acute inflammatory response that involves the
      transcription factor nuclear factor (NF)-kappaB. In addition to being a primary
      regulator of pro-inflammatory gene expression, NF-kappaB may play other roles in
      the hepatic response to I/R, such as mediating the expression of anti-apoptotic
      genes, preventing the accumulation of damaging reactive oxygen species,
      facilitating liver regeneration, and mediating the protective effects of ischemic
      preconditioning. In the present study, we review the diverse functions of NF
      kappaB during hepatic I/R injury.

PMID- 18034830
TI  - Simplified characterization through site-specific protease-mediated release of
      affinity proteins selected by staphylococcal display.
AB  - The production of candidate affinity proteins in a soluble form, for downstream
      characterization, is often a time-consuming step in combinatorial protein
      engineering methods. Here, a novel approach for efficient production of candidate
      clones is described based on direct cleavage of the affinity protein from the
      surface of Staphylococcus carnosus, followed by affinity purification. To find a
      suitable strategy, three new fusion protein constructs were created, introducing
      a protease site for specific cleavage and purification tags for affinity
      chromatography purifications into the staphylococcal display vector. The three
      modified strains were evaluated in terms of transformation frequency, surface
      expression level and protease cleavage efficiency. A protocol for efficient
      affinity purification of protease-released affinity proteins using the introduced
      fusion-tags was successfully used, and the functionality of protease-treated and
      purified proteins was verified in a biosensor assay. To evaluate the devised
      method, a previously selected HER2-specific affibody was produced applying the
      new principle and was used to analyze HER2 expression on human breast cancer
      cells.

PMID- 18034831
TI  - Regulation of urease gene of Actinomyces naeslundii in biofilms in response to
      environmental factors.
AB  - The metabolism of urea by urease enzymes of oral bacteria has a profound
      influence on oral biofilm pH homeostasis and oral microbial ecology, and
      Actinomyces naeslundii is an important ureolytic organism in the oral cavity. To
      gain an insight into the regulation of urease gene expression in cells of A.
      naeslundii growing in biofilms under different environmental conditions, the
      behavior of A. naeslundii ATCC12104 was examined in in vitro biofilms. The strain
      was grown in a chemostat biofilm reactor, and at a quasi-steady state, the urease
      activity of biofilm cells was measured and transcription of ureC gene was
      detected with Taqman quantitative PCR. The effect of environmental changes on
      urease expression was examined by varying the environmental pH, dilution rate,
      carbohydrate and nitrogen availability of the fluid phase of the culture. The
      results showed that the conditions of neutral pH, fast dilution rate, increased
      carbohydrate supply or low nitrogen supply in the medium all resulted in
      enhancement of urease activity in biofilm cells. But only low nitrogen
      availability and a fast dilution rate were observed to lead to an increase in
      ureC mRNA levels. This suggests that nitrogen availability and dilution rate can
      influence the urease activity of A. naeslundii by modulating ureC gene
      transcription.

PMID- 18034832
TI  - Functional analysis of a novel ABC transporter ABC4 from Magnaporthe grisea.
AB  - The ATP-binding cassette (ABC) superfamily of membrane transporters has been
      implicated to play a role in pathogenesis in various phytopathogenic fungi. In an
      insertional mutagenesis screen for pathogenicity mutants of Magnaporthe grisea
      obtained via Agrobacterium tumefaciens-mediated transformation (ATMT), a novel
      gene belonging to the ABC transporter family was identified. The gene ABC4 was
      predicted to be 5045 bp in length coding for a protein of 1654 amino acids. The
      mutant did not form functional appressoria and was nonpathogenic. When compared
      with wild type, the mutant showed increased sensitivity to certain antifungal
      compounds and phytoalexins, implying the role of ABC4 in multidrug resistance
      (MDR) as well as establishment in the host. Reverse transcriptase PCR showed the
      expression of ABC4 in wild-type strain while it was absent in the mutant abc4. In
      real-time PCR, the expression of ABC4 was seen to be enhanced in the presence of
      various drugs tested. The data suggests that ABC4 is required for the
      pathogenicity of M. grisea, helping the fungus to cope with the cytotoxic
      environment during infection.

PMID- 18034833
TI  - Bacterial endophytes: recent developments and applications.
AB  - Endophytic bacteria have been found in virtually every plant studied, where they
      colonize the internal tissues of their host plant and can form a range of
      different relationships including symbiotic, mutualistic, commensalistic and
      trophobiotic. Most endophytes appear to originate from the rhizosphere or
      phyllosphere; however, some may be transmitted through the seed. Endophytic
      bacteria can promote plant growth and yield and can act as biocontrol agents.
      Endophytes can also be beneficial to their host by producing a range of natural
      products that could be harnessed for potential use in medicine, agriculture or
      industry. In addition, it has been shown that they have the potential to remove
      soil contaminants by enhancing phytoremediation and may play a role in soil
      fertility through phosphate solubilization and nitrogen fixation. There is
      increasing interest in developing the potential biotechnological applications of
      endophytes for improving phytoremediation and the sustainable production of
      nonfood crops for biomass and biofuel production.

PMID- 18034834
TI  - Establishment and characterization of dual-species biofilms formed from a 3,5
      dinitrobenzoic-degrading strain and bacteria with high biofilm-forming
      capabilities.
AB  - In this study, the possibility of establishing a dual-species biofilm from a
      bacterium with a high biofilm-forming capability and a 3,5-dinitrobenzoic acid
      (3,5-DNBA)-degrading bacterium, Comamonas testosteroni A3, was investigated. Our
      results showed that the combinations of strain A3 with each of five strains with
      a high biofilm-forming capability (Pseudomonas sp. M8, Pseudomonas putida M9,
      Bacillus cereus M19, Pseudomonas plecoglossicida M21 and Aeromonas hydrophila
      M22) presented different levels of enhancement regarding biofilm-forming
      capability. Among these culture combinations, the 24-h dual-species biofilms
      established by C. testosteroni A3 with P. putida M9 and A. hydrophila M22 showed
      the strongest resistance to 3,5-DNBA shock loading, as demonstrated by six
      successive replacements with DMM2 synthetic wastewater. The degradation rates of
      3,5-DNBA by these two culture combinations reached 63.3-91.6% and 70.7-89.4%,
      respectively, within 6 h of every replacement. Using the gfp-tagged strain M22
      and confocal laser scanning microscopy, the immobilization of A3 cells in the
      dual-species biofilm was confirmed. We thus demonstrated that, during wastewater
      treatment processes, it is possible to immobilize degrader bacteria with bacteria
      with a high biofilm-forming capability and to enable them to develop into the
      mixed microbial flora. This may be a simple and economical method that represents
      a novel strategy for effective bioaugmentation.

PMID- 18034835
TI  - Prevalence of pSmeSM11a-like plasmids in indigenous Sinorhizobium meliloti
      strains isolated in the course of a field release experiment with genetically
      modified S. meliloti strains.
AB  - Plasmid pSmeSM11a, residing in the indigenous Sinorhizobium meliloti strain SM11
      originating from a field in Strassmoos (Bavaria, Germany), was analysed
      previously at the genomic level. Thirty-seven indigenous S. meliloti strains,
      originating from two different locations in Germany, were screened for genes
      identified previously on pSmeSM11a. Seven of these strains harbour accessory
      plasmids that are very similar to pSmeSM11a. The identified pSmeSM11a-like
      plasmids are c. 130-150 kb in size and possess nearly identical restriction
      profiles. Up to 30 genes identified previously on pSmeSM11a could be detected on
      these plasmids by hybridisation experiments, e.g., the nodulation genes nodP and
      nodQ, the ethylene level modulation gene acdS and the taurine metabolism gene
      tauD. A few pSmeSM11a genes were also detected on other plasmids. The reference
      plasmid pSmeSM11a contains a region that is similar to a segment of S. meliloti
      strain Rm1021 pSymA. Regions with similarity to pSymA were also detected on the
      aforementioned seven pSmeSM11a-like plasmids. The specifications of these regions
      are nearly identical to the one on pSmeSM11a and differ from Rm1021 pSymA as
      determined by nucleotide sequence analysis. Two further plasmids similar to
      pSmeSM11a completely lack the pSymA-region. Those strains carrying accessory
      plasmids that contain the acdS gene encoding 1-aminocyclopropane-1-carboxylate
      deaminase are able to grow on 1-aminocyclopropane-1-carboxylate as the sole
      source of nitrogen, demonstrating functionality of the acdS gene product. About
      36% of the analysed plasmids, including three pSmeSM11a-like plasmids, could be
      transferred to another S. meliloti recipient strain, allowing for their
      dissemination in S. meliloti populations.

PMID- 18034836
TI  - Epidermal chemokines and modulation by antihistamines, antibiotics and
      antifungals.
AB  - Growing evidence has demonstrated that chemokines released from epidermal cells
      control inflammatory skin diseases. Keratinocytes elaborate both Th1- and Th2
      associated chemokines, although the former is more abundantly produced than the
      latter. Downmodulation of keratinocyte production of chemokines is one of the
      therapeutic approaches for cutaneous inflammatory disorders. Recent observations
      have shown that keratinocyte chemokine production can be modulated by well-used
      drugs, including antihistamines, antibiotics and antifungals. Utilization of the
      beneficial side effects of these drugs may by clinically valuable.

PMID- 18034837
TI  - Response of a rocky intertidal ecosystem engineer and community dominant to
      climate change.
AB  - To evaluate how climate change might impact a competitively dominant ecological
      engineer, we analysed the growth response of the mussel Mytilus californianus to
      climate patterns [El Nino-Southern Oscillation, Pacific Decadal Oscillation
      (PDO)]. Mussels grew faster during warmer climatic events. Growth was initially
      faster on a more productive cape compared to a less productive cape. Growth rates
      at the two capes merged in 2002, coincidentally with a several year-long shift
      from warm to cool PDO conditions. To determine the mechanism underlying this
      response, we examined growth responses to intertidal sea and air temperatures,
      phytoplankton, sea level and tide height. Together, water temperature (32%) and
      food (12.5%) explained 44.5% of the variance in mussel growth; contributions of
      other factors were not significant. In turn, water temperature and food respond
      to climate-driven variation in upwelling and other, unknown factors.
      Understanding responses of ecosystem engineers to climate change will require
      knowing direct thermal effects and indirect effects of factors altered by
      temperature change.

PMID- 18034838
TI  - The implicit assumption of symmetry and the species abundance distribution.
AB  - Species abundance distributions (SADs) have played a historical role in the
      development of community ecology. They summarize information about the number and
      the relative abundance of the species encountered in a sample from a given
      community. For years ecologists have developed theory to characterize species
      abundance patterns, and the study of these patterns has received special
      attention in recent years. In particular, ecologists have developed statistical
      sampling theories to predict the SAD expected in a sample taken from a region.
      Here, we emphasize an important limitation of all current sampling theories: they
      ignore species identity. We present an alternative formulation of statistical
      sampling theory that incorporates species asymmetries in sampling and dynamics,
      and relate, in a general way, the community-level SAD to the distribution of
      population abundances of the species integrating the community. We illustrate the
      theory on a stochastic community model that can accommodate species asymmetry.
      Finally, we discuss the potentially important role of species asymmetries in
      shaping recently observed multi-humped SADs and in comparisons of the relative
      success of niche and neutral theories at predicting SADs.

PMID- 18034839
TI  - PEGylation improves the hypoglycaemic efficacy of intranasally administered
      glucagon-like peptide-1 in type 2 diabetic db/db mice.
AB  - AIMS: PEGylation - covalent modification of therapeutic peptides with
      polyethylene glycol (PEG) - is viewed as an effective way of prolonging the short
      lifetime of glucagon-like peptide-1 (GLP-1). In this study, we investigated the
      hypoglycaemic efficacies of PEGylated GLP-1s administered intranasally in type 2
      diabetic db/db mice. METHODS: Three types of site-specific (Lys(34)) PEGylated
      GLP-1 analogues (PEG molecular weight: 1, 2 or 5 kDa) were synthesized. Their
      metabolic stabilities were evaluated in nasal mucosa enzyme pools. Oral glucose
      tolerance test was conducted 30, 60 and 120 min after intranasally administering
      these analogues in type 2 diabetic db/db mice. RESULTS: PEGylated GLP-1 analogues
      were found to have significantly longer half-lives than native GLP-1 in nasal
      mucosa enzymes (2.4-fold to 11.0-fold, p < 0.005). Non-PEGylated GLP-1 at 100
      nmol/kg was not found to have marked efficacy irrespective of nasal
      administration time [total hypoglycaemic degree (HD(total)) values 2.8-17.3%]. On
      the contrary, PEGylated GLP-1s (100 nmol/kg) showed obvious efficacies with
      maximum HD(total) values of >51.8 +/- 5.8% (p < 0.005 vs. GLP-1). CONCLUSION:
      This study highlights the pharmacological potential of intranasally administered
      PEGylated GLP-1s in terms of stabilizing postprandial hyperglycaemia in type 2
      diabetic patients.

PMID- 18034841
TI  - Management of thiazolidinedione-induced oedema: minimizing collateral damage.

PMID- 18034842
TI  - Efficacy and tolerability of vildagliptin vs. pioglitazone when added to
      metformin: a 24-week, randomized, double-blind study.
AB  - AIM: The aim of this study was to compare the efficacy and tolerability of
      vildagliptin vs. pioglitazone as add-on therapy in patients with type 2 diabetes
      inadequately controlled with metformin monotherapy. METHODS: This 24-week,
      multicentre, double-blind, randomized, active-controlled study compared
      vildagliptin (100 mg daily, given as equally divided doses, n = 295) and
      pioglitazone (30 mg daily, given as a single q.d. dose, n = 281) in patients with
      inadequate glycaemic control (A1C 7.5-11%) while receiving a stable metformin
      dose (> or =1500 mg daily). The adjusted mean changes from baseline to study
      endpoint (AMDelta) in A1C, fasting plasma glucose (FPG), fasting lipids and body
      weight were compared by analysis of covariance. RESULTS: When added to a stable
      dose of metformin (mean dose at baseline >2000 mg/day), both vildagliptin and
      pioglitazone decreased A1C (AMDelta = -0.9 +/- 0.1% and -1.0 +/- 0.1%,
      respectively) from identical baseline values (8.4 +/- 0.1%). The between-group
      difference in AMDelta A1C was 0.1 +/- 0.1%, and non-inferiority of vildagliptin
      to pioglitazone was established at both 0.4 and 0.3% margins for upper limit of
      the 95% confidence intervals. Pioglitazone decreased FPG (AMDelta = -2.1 +/- 0.1
      mmol/l) to a greater extent than vildagliptin (AMDelta = -1.4 +/- 0.1 mmol/l),
      but only pioglitazone increased body weight (AMDelta = +1.9 +/- 0.2 kg: between
      group difference = -1.6 +/- 0.3 kg, p < 0.001). Adverse events (AEs) were
      reported by 60% of vildagliptin-treated patients and by 56.4% of pioglitazone
      treated patients; serious AEs were reported by 2.0 and 4.6% of patients receiving
      vildagliptin and pioglitazone respectively. Mild hypoglycaemia was reported by
      one patient (0.3%) in the vildagliptin group and by no patients receiving
      pioglitazone. CONCLUSIONS: When added to metformin, the efficacy of vildagliptin
      is non-inferior to that of pioglitazone. The treatments were similarly well
      tolerated, but only pioglitazone increased body weight.

PMID- 18034843
TI  - Effect of high-fat diet on glucose homeostasis and gene expression in glucokinase
      knockout mice.
AB  - AIM: We have generated a heterozygous glucokinase knockout mouse (gk(del/wt)),
      upon which we investigated the effect of high-fat diet (HFD) with respect to
      metabolic control and both hepatic and beta-cell gene expression. We also
      investigated the in vitro efficacy of a glucokinase activator (GKA) on glucose
      stimulated insulin secretion (GSIS) in gk(del/wt)mouse islets. METHODS: Male
      gk(del/wt)and gk(wt/wt)mice were grouped (n = 8-10) at 10 weeks of age and fed
      HFD or chow diet (CD) for 10 weeks. Multiple parameters including blood glucose,
      plasma insulin and glucose tolerance were assessed. Further animal groups were
      used for in vitro GSIS and islet and liver gene expression analysis. RESULTS AND
      CONCLUSIONS: gk(del/wt)mice showed early-onset persistent hyperglycaemia, raised
      glycated haemoglobin levels, impaired GSIS and glucose tolerance but no change in
      plasma cholesterol, non-esterified fatty acids or triglyceride levels. After HFD
      feeding, insulin levels of gk(del/wt)mice were less than half that of
      gk(wt/wt)mice, although they were equivalent to gk(wt/wt)mice on CD. While
      gk(wt/wt)mice maintained moderate hyperglycaemia, gk(del/wt)mice became overtly
      diabetic, with worsened glucose tolerance. A GKA (GKA50) increased GSIS, at 10 mM
      glucose, in gk(del/wt)mice to an extent at least as great as that seen in
      gk(wt/wt)mice on both CD and HFD. gk(del/wt)mice showed only a small number of
      changes in gene expression compared with gk(wt/wt)mice. We propose the high fat
      fed gk(del/wt)mouse as a model of type 2 diabetes and report retained efficacy of
      a GKA on in vitro GSIS.

PMID- 18034844
TI  - Effects of insulin resistance on endothelial function: possible mechanisms and
      clinical implications.
AB  - Insulin resistance (IR) is defined as a reduced responsiveness of peripheral
      tissues to the effects of the hormone, referring to abated ability of insulin in
      stimulating glucose uptake in peripheral tissues and in inhibiting hepatic
      glucose output. Insulin has both a vasodilatory effect, which is largely
      endothelium dependent through the release of nitric oxide, and a vasoconstrictory
      effect through the stimulation of the sympathetic nervous system and the release
      of endothelin-1. IR and endothelial dysfunction (ED) are not only linked by
      common pathogenetic mechanisms, involving deranged insulin signalling pathways,
      but also by other, indirect to the hormone's actions, mechanisms. Different
      treatment modalities have been proposed to affect positively both the metabolic
      effects of insulin and ED. Weight loss has been shown to improve sensitivity to
      insulin as a result of either altered diet or exercise. Exercise has favourable
      effects on endothelial function in normal states and in states of disease, in men
      and women, and throughout the age spectrum and, hence, in IR states. Metformin
      improves sensitivity to insulin and most likely affects positively ED. Studies
      have shown that inhibitors of the renin-angiotensin system alter IR favourably,
      while Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor
      type II (ATII) inhibitors improve ED. Ongoing studies are expected to shed more
      light on the issue of whether treatment with the thiazolidinediones results in
      improvement of endothelial function, along with the accepted function of
      improving insulin sensitivity. Finally, improved endothelial function by such
      treatments is not in itself proof of reduced risk for atherosclerosis; this
      remains to be directly tested in clinical trials.

PMID- 18034845
TI  - The effects of obesity and non-pharmacological weight loss on vascular and
      ventricular function and structure.
AB  - AIMS: The mechanisms by which obesity confers increased cardiovascular risk and
      the effects of moderate weight loss on cardiovascular health are incompletely
      understood. We sought to characterize the preclinical changes in cardiac and
      vascular health that accompany obesity and the influence of lifestyle
      modification on these parameters. METHODS: Preclinical markers of vasculopathy in
      resistance vessels and conduit arteries and left ventricular structure and
      function were assessed in 39 obese subjects (BMI > 30 kg/m(2)) and 11 healthy
      weight controls. The influence of serum on cellular adhesion molecule (CAM)
      expression on human endothelial cells was studied ex vivo in a subgroup of 13
      obese and nine healthy weight subjects. These analyses were repeated in all 17 of
      the obese subjects who complied with 4-9 months of lifestyle modification
      treatment (six with weight loss >5% and 11 with weight loss <5%). RESULTS:
      Compared with healthy weight controls, obese subjects had decreased peak
      hyperaemic forearm blood flow (p = 0.015), increased carotid intima-media
      thickness (p = 0.009), increased left ventricular wall thickness and volume and
      evidence of systolic and diastolic dysfunction as assessed using tissue Doppler
      imaging (S', p = 0.09; E'/A', p = 0.02), and serum from obese subjects increased
      the intercellular CAM-1 expression on human endothelial cells (p = 0.009).
      However, arterial endothelial function assessed by flow-mediated dilatation was
      not altered (p = 0.99). Lifestyle modification treatment resulted in potentially
      beneficial changes in fibrinogen (p = 0.003), HDL cholesterol (p = 0.05) and
      soluble vascular CAM-1 (p = 0.06). In subjects with weight loss greater than 5%
      of body weight, there was also a decrease in low-level inflammation (high
      sensitivity C-reactive protein, p = 0.05), lipid peroxidation (thiobarbituric
      acid-reactive substances, p = 0.05) and triglycerides (p = 0.07). CONCLUSIONS:
      Obesity is associated with widespread alterations in cardiac and vascular
      structure and function. Moderate short-term weight loss by lifestyle modification
      results in some beneficial changes in serum profile; however, these are not
      accompanied by significant alterations to either cardiac or vascular structure
      and function.

PMID- 18034846
TI  - Transferring to insulin detemir from NPH insulin or insulin glargine in type 2
      diabetes patients on basal-only therapy with oral antidiabetic drugs improves
      glycaemic control and reduces weight gain and risk of hypoglycaemia: 14-week
      follow-up data from PREDICTIVE.
AB  - AIM: The aim of this study was to evaluate the safety and efficacy of insulin
      detemir in type 2 diabetes patients previously receiving NPH insulin (NPH group,
      n = 175) or insulin glargine (glargine group, n = 118) in combination with oral
      antidiabetic drugs (OADs). METHODS: Patients were transferred to insulin detemir,
      while the OAD regimen and number of injections remained the same. The incidence
      of serious adverse drug reactions, including major hypoglycaemia, and haemoglobin
      A(1c) (HbA(1c)), fasting glucose, within-patient fasting glucose variability and
      body weight change were measured at 14 weeks. RESULTS: Glycaemic control improved
      in both NPH (HbA(1c) = -0.2%, p < 0.05; fasting glucose -1.0 mmol/l, p < 0.0001)
      and glargine (HbA(1c) = -0.6%, p < 0.0001; fasting glucose -1.4 mmol/l, p <
      0.0001) groups, including a reduction in fasting glucose variability (p < 0.01
      for both). The incidence of total and nocturnal hypoglycaemia was reduced in both
      NPH and glargine groups. The incidence of major hypoglycaemia was low and did not
      change significantly during the follow-up period. Mean body weight was
      significantly reduced in the NPH (-0.7 kg, p < 0.01) and glargine (-0.5 kg, p <
      0.05) groups. CONCLUSIONS: These results indicate that in type 2 diabetes,
      transferring from other basal insulins to insulin detemir in combination with
      OADs was associated with improvements in glycaemic control, which were
      accompanied by a reduced risk of hypoglycaemia and a reduction in body weight.

PMID- 18034847
TI  - Effects of aspirin on serum C-reactive protein and interleukin-6 levels in
      patients with type 2 diabetes without cardiovascular disease: a randomized
      placebo-controlled crossover trial.
AB  - AIM: Low-grade inflammation plays a pivotal role in atherogenesis in type 2
      diabetes. Next to its antithrombotic effects, several lines of evidence
      demonstrate anti-inflammatory properties of aspirin. We determined the effects of
      aspirin on inflammation - represented by C-reactive protein (CRP) and interleukin
      6 (IL-6) - in type 2 diabetic subjects without cardiovascular disease and
      assessed differential effects of aspirin 300 mg compared with 100 mg. METHODS: A
      randomized, placebo-controlled, double-blind, crossover trial was performed in 40
      type 2 diabetic patients. In two periods of 6 weeks, patients used 100 or 300 mg
      aspirin and placebo. Plasma CRP and IL-6 levels were measured before and after
      both periods. RESULTS: Use of aspirin resulted in a CRP reduction of 1.23 +/-
      1.02 mg/l (mean +/- s.e.m.), whereas use of placebo resulted in a mean increase
      of 0.04 +/- 1.32 mg/l (P = 0.366). Aspirin reduced IL-6 with 0.7 +/- 0.5 pg/ml,
      whereas use of placebo resulted in a mean increase of 0.2 +/- 0.8 pg/ml (P =
      0.302). There were no significant differences in effects on CRP and IL-6 between
      100 and 300 mg aspirin. CONCLUSIONS: Our results indicate that a 6-week course of
      aspirin does not improve low-grade inflammation in patients with type 2 diabetes
      without cardiovascular disease, although a modest effect could not be excluded.
      No significant differential effects between aspirin 100 and 300 mg were found.

PMID- 18034848
TI  - Pulse wave analysis on fingertip arterial pressure: effects of age, gender and
      stressors on reflected waves and their relation to brachial and femoral artery
      blood flow.
AB  - OBJECTIVES: Analysis of the contour of the arterial pressure pulse (pulse wave
      analysis; PWA) adds information about arterial stiffness etc., beyond that
      obtained from absolute pressures. Peripheral pulses normally show an anterograde
      systolic peak and two reflected peaks: one in systole and one in diastole. The
      amplitudes and timings of these were estimated from finger pressure recordings in
      three study groups. We studied the usefulness of continuous digital pressures for
      PWA. METHODS: First, PWA from intra-arterial (brachial) and non-invasive finger
      pressure recordings was compared. Secondly, stress-induced (mental arithmetics
      and cold pressor test) changes in pressure pulse reflection were compared with
      blood flow changes in brachial and femoral arteries (ultrasound). Thirdly, the
      influence of age and gender on digital pulse pressures was investigated at rest
      and during exercise. RESULTS AND CONCLUSION: Pulse wave analysis results from
      brachial and digital pressures correlated strongly. Stress induced changes in
      systolic reflection were associated with changes in brachial artery flow
      patterns, whereas diastolic reflection was associated with femoral artery flow
      changes. At rest, age increased systolic reflection without affecting diastolic
      reflection. Exercise increased systolic reflection and reduced diastolic
      reflection more in older subjects (>40 years) than in younger (<40 years). In
      conclusion, PWA from continuous, digital pressure recordings is a convenient
      technique to study the arterial function at rest and during exposure to stressors
      in broad populations. The two reflected waves are differently regulated, which
      may indicate different anatomical origin.

PMID- 18034849
TI  - Allergic rhinitis with hyper-responsiveness differ from asthma in degree of
      peripheral obstruction during metacholine challenge test.
AB  - Allergic rhinitis (AR) is a risk factor for developing clinical asthma. Moreover,
      AR is often associated with bronchial hyper-responsiveness (BHR). The aim of this
      study was to compare the degree of involvement of the peripheral airways during
      metacholine (MCh) challenge test in asthmatics and patients with AR with or
      without BHR by using the impulse oscillometry (IOS) technique. Fifty-three
      patients with seasonal AR were investigated with MCh challenge test and IOS.
      Thirteen healthy non-reactive subjects served as controls. MCh challenge test was
      performed, cut-off value FEV1PD20 2000 microg. Linear regression analysis was
      used to calculate a MCh/FEV1 slope (Slope-FEV1MCh), which was used as an index of
      BHR. IOS was performed, measuring respiratory resistance and reactance during the
      MCh challenge test. Twenty-six subjects had both AR and asthma symptoms, 27
      patients reported AR only, without asthma symptoms, 17 (63%) manifested BHR by
      spirometric criteria. Patients with AR and symptoms of asthma manifested greater
      peripheral airway obstruction compared to those with AR only with BHR. Increased
      peripheral obstruction in the asthmatic group compared to patients with AR and
      BHR may explain previous findings that asthmatics perceive greater airway
      obstruction during MCh challenge tests.

PMID- 18034850
TI  - Periodontal disease as a risk factor for adverse pregnancy outcomes: a
      prospective cohort study.
AB  - AIM: The aim of this study was to determine the association between periodontitis
      and the incidence of preterm birth (PB), low birth weight (LBW) and preterm low
      birth weight (PLBW) MATERIAL AND METHODS: One thousand and ninety-six women were
      enrolled. Periodontal data, pregnancy outcome variables and information on other
      factors that may influence adverse pregnancy outcomes were collected. Data were
      analysed using a logistic regression model. RESULTS: The incidence of PB and LBW
      was 6.6% and 6.0%, respectively. The incidence of PLBW was 3.3%. PB was related
      to mother's age, systemic diseases, onset of prenatal care, previous PBs,
      complications of pregnancy, type of delivery, the presence of untreated caries
      and the presence of periodontitis (odds ratio 1.77, 95% confidence interval: 1.08
      2.88). LBW was related to mother's smoking habits, ethnicity, systemic diseases,
      previous LBW babies, complications of pregnancy and type of delivery. PLBW was
      related to mother's age, onset of prenatal care, systemic diseases, previous LBW
      babies, complications of pregnancy and type of delivery. CONCLUSIONS: The factors
      involved in many cases of adverse pregnancy outcomes have still not being
      identified, although systemic infections may play a role. This study found a
      modest association between periodontitis and PB. Further research is required to
      establish whether periodontitis is a risk factor for PB and/or LBW.

PMID- 18034851
TI  - Impact of local and systemic factors on the incidence of failures up to abutment
      connection with modified surface oral implants.
AB  - AIM: This study aimed to assess the influence of systemic and local bone and
      intra-oral factors on the occurrence of early TiUnite implant failures. MATERIAL
      AND METHODS: A total of 283 consecutive patients (187 females; mean age 56.2),
      who received a total of 720 TiUnite implants, at the Department of Periodontology
      of the University Hospital of the Catholic University of Leuven, were
      prospectively followed. The following aspects were particularly assessed:
      hypertension, cardiac problems, gastric problems, osteoporosis, hypo- or
      hyperthyroid, hypercholesterolaemia, asthma, diabetes types I or II, Crohn's
      disease, rheumatoid arthritis, chemotherapy, hysterectomy and intake of
      medication (antidepressants, steroids, hormone replacement), radiotherapy of the
      concerned area, breach of sterility during surgery, implant parameters, bone
      (quality, quantity, dehiscence or perforation), type of edentulism, antibiotics
      prescription, fenestration of the implant in the sinus/nasal cavity, immediate
      implant placement, apical lesion detection and insertion torque. RESULTS AND
      CONCLUSION: A global failure rate of 1.9% was recorded. Owing to the very few
      failures, no definitive conclusion concerning statistical significance can be
      achieved. However, a tendency for more failures was noticed for apical lesions,
      vicinity with natural dentition, smoking, hormone replacement, gastric problems,
      Crohn's disease, diabetes I and radical hysterectomy.

PMID- 18034852
TI  - Total protein concentration and total bacterial load as measures of residual
      interproximal plaque in comparative clinical trials.
AB  - AIM: Establish total protein concentration and total bacterial load as
      quantitative measures of residual interproximal plaque (IPP) in a clinical model
      designed to evaluate oral hygiene interventions. MATERIAL AND METHODS: This
      clinical model was a randomized, examiner and laboratory technician-blinded,
      parallel-design study whereby levels of residual IPP were compared for subjects
      using a manual toothbrush or a toothbrush+floss. Differences between
      interventions were compared after 7 and 21 days of use. Protein concentration was
      measured using 3-(4-carboxybenzoyl) quinoline-2-carboxaldehyde in a fluorescence
      microplate format and bacterial load was assessed by quantitative real-time PCR
      with universal primers specific for 16S rRNA and detected by SYBR Green. ancova
      was used to assess the statistical significance of the differences between
      interventions while clinical relevance was evaluated by a statistical model
      described by Man-Son-Hing et al. 2002. RESULTS: Ninety-three subjects completed
      the study. Significant differences between interventions, using both outcome
      measures, were observed after 7 and 21 days. The difference between interventions
      by total protein concentration were further determined to be clinically relevant.
      CONCLUSIONS: Only total protein concentration provided both statistically
      significant and clinically relevant differences between two clinically distinct
      oral hygiene interventions in this clinical model for evaluating IPP.

PMID- 18034853
TI  - Effect of platelet-rich plasma on the healing of intrabony defects treated with
      an enamel matrix protein derivative and a natural bone mineral.
AB  - BACKGROUND: Regenerative periodontal surgery utilizing a combination of an enamel
      matrix protein derivative (EMD) and a natural bone mineral (NBM) and platelet
      rich plasma (PRP) has been shown to enhance the outcomes of regenerative surgery
      significantly. At present, it is unknown whether root conditioning with EMD,
      followed by defect fill with a combination of NBM+PRP may additionally enhance
      the clinical results obtained with EMD+NBM. AIM: To compare clinically the
      treatment of deep intrabony defects with either EMD+NBM+PRP or EMD+NBM. MATERIAL
      AND METHODS: Twenty-six patients suffering from advanced chronic periodontitis,
      and each of whom displayed one advanced intrabony defect were randomly treated
      with either EMD+NBM+PRP (test) or EMD+NBM (control). The following clinical
      parameters were evaluated at baseline and at 1 year after treatment: plaque index
      (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD),
      gingival recession (GR) and clinical attachment level (CAL). The primary outcome
      variable was CAL. RESULTS: Healing was uneventful in all patients. At 1 year
      after therapy, the test sites showed a reduction in mean PD from 8.8+/-1.9 mm to
      3.1+/-0.9 mm ( p<0.001) and a change in mean CAL from 10.8+/-2.0 mm to 6.0+/-1.5
      mm ( p<0.001). In the control group the mean PD was reduced from 8.8+/-2.0 mm to
      2.8+/-1.6 mm ( p<0.001) and the mean CAL changed from 10.5+/-1.6 mm to 5.5+/-1.4
      mm ( p<0.001). CAL gains of > or =4 mm were measured in 77% (i.e. in 10 out of 13
      defects) of the cases treated with EMD+NBM+PRP and in 100% (i.e. in all 13
      defects) treated with EMD+NBM. No statistically significant differences in any of
      the investigated parameters were observed between the two groups. CONCLUSIONS:
      Within its limits, the present study has shown that (i) 1 year after regenerative
      surgery, both treatments resulted in statistically significant PD reductions and
      CAL gains and (ii) the use of PRP failed to enhance the results obtained with
      EMD+NBM.

PMID- 18034854
TI  - Bone regeneration in dehiscence-type defects at non-submerged and submerged
      chemically modified (SLActive) and conventional SLA titanium implants: an
      immunohistochemical study in dogs.
AB  - OBJECTIVES: The aim of the present study was to evaluate bone regeneration in
      dehiscence-type defects at non-submerged and submerged titanium implants with
      chemically modified (mod) and conventional sandblasted/acid-etched (SLA)
      surfaces. MATERIAL AND METHODS: Standardized buccal dehiscence defects were
      surgically created following implant site preparation in both the upper and lower
      jaws of 12 beagle dogs. Both types of implants were randomly assigned to either a
      non-submerged or a submerged healing procedure. After 1, 2, 4, and 8 weeks,
      dissected blocks were processed for histomorphometrical [e.g. new bone height
      (NBH), per cent linear fill (PLF), percentage of bone to implant contact (BIC-D),
      area of new bone fill (BF)] and immunohistochemical analysis. RESULTS: At 8
      weeks, non-submerged and submerged SLA implants revealed significantly lower mean
      NBH (1.1+/-0.8-1.9+/-1.2 mm), PLF (27.7+/-20.3-46.0+/-28.5%), BIC-D (26.8+/-10.4
      46.2+/-16.2%), and BF (1.3+/-0.9-3.4+/-2.8 mm(2)) values than respective modSLA
      implants [NBH (2.6+/-0.8-4.3+/-0.1 mm), PLF (64.2+/-19.4-107.2+/-4.7%), BIC-D
      (67.5+/-18.8-82.1+/-14.8%), BF (2.9+/-1.0-6.7+/-1.1 mm(2))]. Within modSLA
      groups, significantly highest BF values were observed at submerged implants.
      CONCLUSION: It was concluded that (i) modSLA titanium surfaces promoted bone
      regeneration in acute-type buccal dehiscence defects and (ii) a submerged healing
      procedure improved the outcome of healing additionally.

PMID- 18034856
TI  - Interaction of alpha1-syntrophin with multiple isoforms of heterotrimeric G
      protein alpha subunits.
AB  - Syntrophins are components of the dystrophin-glycoprotein complex of the plasma
      membrane in muscular and neuronal cells, and recruit signaling proteins such as
      neuronal nitric oxide synthase via their multiple protein-protein interaction
      motifs. In this study, we found that alpha1-syntrophin binds to various subtypes
      of guanine nucleotide-binding protein alpha subunits (Galpha). A pull-down
      analysis using full-length recombinant alpha1-syntrophin and MS analysis showed
      that alpha1-syntrophin was coprecipitated with several isoforms of Galpha
      proteins in addition to known binding partners such as dystrobrevin and neuronal
      nitric oxide synthase. Further analysis using recombinant Galpha isoforms showed
      that alpha1-syntrophin associates with at least Galphai, Galphao, Galphas and
      Galphaq subtypes. The region of alpha1-syntrophin required for its interaction
      with Galphas was determined as the N-terminal half of the first pleckstrin
      homology domain. In addition, the syntrophin unique domain of alpha1-syntrophin
      was suggested to contribute to this interaction. In COS-7 cells, downregulation
      of alpha1-syntrophin by RNAi resulted in enhanced cAMP production and cAMP
      response element-binding protein phosphorylation induced by isoproterenol
      treatment. These results suggest that alpha1-syntrophin provides a scaffold for
      the Galpha family of heterotrimeric G proteins in the brain to regulate the
      efficiency of signal transduction evoked by G-protein-coupled receptors.

PMID- 18034855
TI  - Protein crystallography for non-crystallographers, or how to get the best (but
      not more) from published macromolecular structures.
AB  - The number of macromolecular structures deposited in the Protein Data Bank now
      exceeds 45,000, with the vast majority determined using crystallographic methods.
      Thousands of studies describing such structures have been published in the
      scientific literature, and 14 Nobel prizes in chemistry or medicine have been
      awarded to protein crystallographers. As important as these structures are for
      understanding the processes that take place in living organisms and also for
      practical applications such as drug design, many non-crystallographers still have
      problems with critical evaluation of the structural literature data. This review
      attempts to provide a brief outline of technical aspects of crystallography and
      to explain the meaning of some parameters that should be evaluated by users of
      macromolecular structures in order to interpret, but not over-interpret, the
      information present in the coordinate files and in their description. A
      discussion of the extent of the information that can be gleaned from the
      coordinates of structures solved at different resolution, as well as problems and
      pitfalls encountered in structure determination and interpretation are also
      covered.

PMID- 18034857
TI  - Seroprevalence and incidence of Toxoplasma gondii infection in the Legnano area
      of Italy.
AB  - The decreasing prevalence of anti-Toxoplasma antibodies in Europe has re-opened
      the question of the appropriateness of serological screening during pregnancy. A
      study of 3426 pregnant women, resident in the Legnano area of Italy, revealed
      that the IgG seroprevalence according to ELISA was 21.5%, and that of IgM
      according to ELISA and enzyme-linked fluorescent assay was 1.2% and 0.9%,
      respectively. The incidence of infection, estimated on the basis of IgG avidity,
      was 0.9%. These results confirm a decrease in the prevalence of IgG, but indicate
      a high incidence of infection, thus suggesting that screening for anti-Toxoplasma
      antibodies during pregnancy should be maintained.

PMID- 18034858
TI  - A first insight into the genetic diversity and population structure of
      Mycobacterium tuberculosis in Zonguldak, Turkey.
AB  - This study evaluated the molecular epidemiology and biodiversity of Mycobacterium
      tuberculosis isolates in Zonguldak, Turkey, and investigated the presence and
      significance of the LAM7-TUR clone by spoligotyping and mycobacterial
      interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) analysis.
      In total, 128 isolates were tested by spoligotyping; 25 selected isolates
      representative of the LAM7-TUR clone and similar types were also tested by MIRU
      VNTR analysis. In total, 47 distinct patterns were revealed by spoligotyping,
      represented by 13 clusters containing between two and 28 isolates (94 isolates in
      total), and 34 unique patterns (a clustering rate of 73%). Using MIRU-VNTR
      analysis, the clustering relationships revealed by spoligotyping were confirmed.
      The most common spoligotyping profile was SIT53, followed by SIT41 (LAM7-TUR) and
      SIT50. The SIT284 clone was another phylogeographically specific clonal complex
      whose presence in Turkey may be endemic. The LAM7-TUR genotype was highly
      prevalent in Zonguldak.

PMID- 18034859
TI  - Prevalence and mechanisms of erythromycin and clindamycin resistance in clinical
      isolates of beta-haemolytic streptococci of Lancefield groups A, B, C and G in
      Seville, Spain.
AB  - Susceptibility to erythromycin and clindamycin was determined in 860 consecutive
      clinical isolates of beta-haemolytic streptococci belonging to groups A (GAS, n =
      134), B (GBS, n = 689), C (GCS, n = 19) and G (GGS, n = 18). Erythromycin
      resistance was 26.1% in GAS, 15.7% in GBS, 5.3% in GCS and 33.3% in GGS. The
      highest rate of clindamycin resistance (33.3%) was in GGS, followed by GBS
      (15.8%), GCS (15.8%) and GAS (5.2%). The M phenotype was predominant in GAS
      (80%), the constitutive MLS(B) phenotype was predominant in GBS (75%), and all
      GGS isolates showed the inducible MLS(B) phenotype. The uncommon erythromycin
      susceptible and clindamycin-resistant phenotype was found in four GBS and two GCS
      isolates.

PMID- 18034860
TI  - Screening for methicillin-resistant Staphylococcus aureus in clinical swabs using
      a high-throughput real-time PCR-based method.
AB  - The presence of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals
      and the community is a serious problem. Accordingly, a comprehensive plan has
      been implemented in the County of Vejle, Denmark, to identify colonised and/or
      infected individuals and to control the spread of MRSA. Since 2005, all patients
      and healthcare personnel have been screened for MRSA colonisation, involving
      analysis of 300-400 samples daily. To deal with this number of samples, a PCR
      based method customised for high-throughput analysis and a system for fast
      reporting of MRSA carrier status were developed. Swab samples were incubated
      overnight in a selective tryptone soya broth and were analysed by PCR the
      following day. Using this strategy, non-colonised individuals were identified
      within 24 h, while MRSA-positive samples were analysed further by traditional
      microbiological methods to determine the resistance pattern. This is a cost
      effective approach, as the greatest expense in hospitals involves the isolation
      of patients of unknown MRSA status. The method was evaluated by testing 2194
      clinical samples, with a sensitivity and specificity of 100% and 94%,
      respectively. The analytical sensitivity was 97%, with 161 of 166 different MRSA
      strains and isolates generating positive results according to PCR analysis. Using
      four control strains, the inter-assay variation was revealed to be a maximum of
      2.6%, indicating good reproducibility.

PMID- 18034861
TI  - Time-trends for Gram-negative and multidrug-resistant Gram-positive bacteria
      associated with nosocomial infections in German intensive care units between 2000
      and 2005.
AB  - This study analysed the time-trends for bacteria associated with nosocomial lower
      respiratory tract infections (LRTIs), bloodstream infections (BSIs) and urinary
      tract infections (UTIs) that were reported to the German Nosocomial Infection
      Surveillance System for intensive care units (ICUs). Data concerning 19 822
      nosocomial infections were submitted by 139 ICUs between 2000 and 2005. There was
      a significant increase in the proportion of Gram-negative bacteria causing LRTIs
      (from 63.9% to 68.4%) and UTIs (from 65.3% to 68.6%). The proportion of BSIs
      caused by Gram-negative bacteria declined significantly, from 36.4% to 22.7%. The
      frequency of methicillin-resistant Staphylococcus aureus among all S. aureus
      isolates increased from 19.8% to 37.2%.

PMID- 18034862
TI  - Streptococcus pneumoniae: proteomics of surface proteins for vaccine development.
AB  - Two formulations of pneumococcal vaccines are currently available to prevent
      invasive disease in adults and children. However, these vaccines will not protect
      against the majority of Streptococcus pneumoniae serotypes. The use of highly
      conserved cell-wall-associated proteins in vaccines may circumvent this problem.
      A proteomics approach was used to identify 270 S. pneumoniae cell-wall-associated
      proteins, which were then screened in a process that included in-silico, in-vitro
      and in-vivo validation criteria. Five potential candidates for inclusion in a
      vaccine were selected, expressed in Escherichia coli, and purified for use in
      immunisation experiments. These proteins were detected in at least 40 different
      serotypes of S. pneumoniae, and were expressed in S. pneumoniae isolates causing
      infection. Two of the five candidate proteins, the putative lipoate protein
      ligase (Lpl) and the ClpP protease, resulted in a reduced CFU titre and a trend
      towards reduced mortality in an animal sepsis model for investigating new S.
      pneumoniae protein vaccines.

PMID- 18034863
TI  - Characterisation of invasive group B streptococci based on investigation of
      surface proteins and genes encoding surface proteins.
AB  - The joint distributions of the six genes bca, bac, epsilon/alp1, alp2, alp3 and
      rib (encoding alpha-C-protein, beta-C-protein, epsilon/Alp1, Alp2, Alp3, and Rib,
      respectively) and the proteins alpha-C-protein, beta-C-protein and Rib were
      investigated in invasive isolates of group B streptococcus (GBS). In total, 297
      invasive isolates (123 from neonates, 174 from adults) from south-west Sweden
      were collected during a 13-year period. Genes were detected using multiplex and
      specific PCRs, and expression of the surface proteins was demonstrated using
      monoclonal antibodies. The genes studied were found alone or in combinations in
      294 (99%) of the invasive isolates. The most common genes were rib (n = 127
      isolates, 43%), alp3 (n = 78, 26%) and epsilon/alp1 (n = 42, 14%). The bac gene
      was never found alone, but was found in combination with one other gene in 36
      isolates. The surface proteins studied were detected alone or in combinations in
      152 (51%) isolates, with the most common being Rib (n = 80, 27%), alpha-C-protein
      (n = 68, 23%) and beta-C-protein (n = 24, 8%). Several genes were associated
      significantly with particular serotypes (e.g., epsilon/alp1 with serotype Ia; bca
      and bac with serotypes Ib and II; rib with serotype III; alp3 with serotype V).
      Overall, it was concluded that demonstration of different genes and surface
      proteins of GBS strains can be useful in epidemiological studies and in
      formulation of vaccines, but disappointingly, no single gene or surface protein
      included in the study was sufficiently common for it to be considered as the
      basis for a successful GBS vaccine.

PMID- 18034864
TI  - Induction of ERK-kinase signalling triggers morphotype-specific killing of
      Candida albicans filaments by human neutrophils.
AB  - Candida albicans is among the most important fungal pathogens in humans.
      Morphological plasticity has been linked to its pathogenic potential as
      filamentous forms are associated with tissue invasion and infection. Here we show
      that human neutrophils discriminate between yeasts and filaments of C. albicans.
      Whereas filaments induced targeted motility, resulting in the establishment of
      close contact between neutrophils and fungal cells, yeast forms were largely
      ignored during coincubation. In transwell assays, C. albicans filaments induced
      significantly higher migratory activity in neutrophils than yeasts. Neutrophil
      motility based on actin rearrangement was essential for killing of C. albicans
      filaments but not involved in killing of yeast forms. Using inhibitors for MAP
      kinase cascades, it was shown that recognition of C. albicans filaments by
      neutrophils is mediated via the MEK/ERK cascade and independent of JNK or p38
      activation. Inhibition of the ERK signalling pathway abolished neutrophil
      migration induced by C. albicans filaments and selectively impaired the ability
      to kill this morphotype. These data show that invasive filamentous forms of C.
      albicans trigger a morphotype-specific activation of neutrophils, which is
      strongly dependent on neutrophil motility. Therefore, human neutrophils are
      capable of sensing C. albicans invasion and initiating an appropriate early
      immune response.

PMID- 18034865
TI  - Host-pathogen interplay and the evolution of bacterial effectors.
AB  - Many bacterial pathogens require a type III secretion system (T3SS) and suite of
      type III secreted effectors (T3SEs) to successfully colonize their hosts, extract
      nutrients and consequently cause disease. T3SEs, in particular, are key
      components of the bacterial arsenal, as they function directly inside the host to
      disrupt or suppress critical components of the defence network. The development
      of host defence and surveillance systems imposes intense selective pressures on
      these bacterial virulence factors, resulting in a host-pathogen co-evolutionary
      arms race. This arms race leaves its genetic signature in the pattern and
      structure of natural genetic variation found in T3SEs, thereby permitting us to
      infer the specific evolutionary processes and pressures driving these
      interactions. In this review, we summarize our current knowledge of T3SS-mediated
      host-pathogen co-evolution. We examine the evolution of the T3SS and the T3SEs
      that traverse it, in both plant and animal pathosystems, and discuss the
      processes that maintain these important pathogenicity determinants within
      pathogen populations. We go on to examine the possible origins of T3SEs, the
      mechanisms that give rise to new T3SEs and the processes that underlie their
      evolution.

PMID- 18034866
TI  - The Vi-capsule prevents Toll-like receptor 4 recognition of Salmonella.
AB  - The viaB locus enables Salmonella enterica serotype Typhi to reduce Toll-like
      receptor (TLR) dependent cytokine production in tissue culture models. This DNA
      region contains genes involved in the regulation (tviA), biosynthesis (tviBCDE)
      and export (vexABCDE) of the Vi capsule. Expression of the Vi capsule in S.
      Typhimurium, but not expression of the TviA regulatory protein, reduced tumour
      necrosis factor-alpha (TNF-alpha) and IL-6 production by murine bone-marrow
      derived macrophages. Production of TNF-alpha and IL-6 was dependent on expression
      of TLR4 as stimulation of macrophages from TLR4(-/-) mice with S. Typhimurium did
      not result in expression of these cytokines. Intraperitoneal infection of mice
      with S. Typhimurium induced expression of TNF-alpha and inducible nitric oxide
      synthase (iNOS) in the liver. Introduction of the cloned viaB region into S.
      Typhimurium reduced TNF-alpha and iNOS expression to levels observed after
      infection with a S. Typhimurium msbB mutant. In contrast, no differences in TNF
      alpha expression between the S. Typhimurium wild type and strains expressing the
      Vi-capsule or carrying a mutation in msbB were observed after infection of TLR4(
      /-) mice. We conclude that the Vi capsule prevents both in vitro and in vivo
      recognition of S. Typhimurium lipopolysaccharide by TLR4.

PMID- 18034867
TI  - Haemodilution induced by hydroxyethyl starches 130/0.4 is similar in septic and
      non-septic patients.
AB  - BACKGROUND: Fluid therapy induces haemodilution related to plasma volume
      expansion. The aim of our study was to compare haemodilution after a single
      hydroxyethyl starches (HES) 130/0.4 infusion in two groups of patients, one with
      and one without sepsis. We hypothesized that a single HES challenge would induce
      similar sustained haemodilution in both groups. METHODS: In this prospective
      preliminary study, patients predicted to require a single further volume-expander
      infusion were included immediately before receiving 500 ml of 6% HES 130/0.4 over
      a 15-min period. No additional fluid was administered over the next 8 h.
      Haematocrit, and serum albumin and protein were determined immediately before HES
      infusion then after 1, 2, 3, 4, and 8 h. RESULTS: Twelve patients were included
      in each group. In both groups, all three haemodilution markers had significantly
      lower values after 1 h than at baseline. None of the values after 1 and 3 h
      differed significantly between the two groups. Neither did any of the other study
      variables show significant differences between the groups with and without
      sepsis. CONCLUSION: We found that a starch-based compound was as effective in
      inducing haemodilution in patients with sepsis as in controls without sepsis,
      suggesting that HES may remain within the intravascular space even in patients
      with sepsis. Haemodilution parameters such as haematocrit, serum albumin and
      serum protein are useful for assessing the duration of plasma volume expansion
      induced by fluid therapy in critically ill patients.

PMID- 18034868
TI  - Impaired glucose tolerance in the R6/1 transgenic mouse model of Huntington's
      disease.
AB  - Previous reports have highlighted a possible link between Huntington's disease
      (HD) and diabetes mellitus (DM), but the association has not been characterised
      in detail. A transgenic mouse model for HD, the R6/2 mouse, also develops
      diabetes. In the present study, we examined the R6/1 mouse, which carries a
      shorter CAG repeat than the R6/2 mouse, and found that, although not diabetic,
      the mice showed several signs of impaired glucose tolerance. First, following
      i.p. glucose injection, the blood glucose concentration was approximately 30%
      higher in young R6/1 mice (10 weeks) compared to wild-type mice (P = 0.004). In
      older mice (38 weeks), glucose tolerance was further impaired in both R6/1 and
      wild-type animals. Second, during glucose challenge, the R6/1 mice reached higher
      plasma insulin levels than wild-type mice, but the peripheral insulin sensitivity
      was normal as measured by injection of human or mouse insulin or when evaluated
      by the quantitative insulin sensitivity check index (QUICKI). Third, the beta
      cell volume was 17% and 39% smaller at 10 and 38 weeks of age, respectively,
      compared to age-matched wild-type littermates and the reduction was not caused by
      apoptosis at either age. Finally, we demonstrated the presence of the HD gene
      product, huntingtin (htt), in both alpha- and beta-cells in R6/1 islets of
      Langerhans. Since pancreatic beta cells and neurons share several common traits,
      clarification of the mechanism associating neurodegenerative diseases with
      diabetes might improve our understanding of the pathogenic events leading to both
      groups of diseases.

PMID- 18034869
TI  - Leptin resistance during pregnancy in the rat.
AB  - The adipose-derived hormone leptin primarily acts in the hypothalamus to decrease
      appetite and increase energy expenditure, thereby maintaining body fat levels
      around a set point. Pregnancy is a physiological state where this feedback
      mechanism is not beneficial. Successful reproductive efforts are highly demanding
      on the resources of the mother; thus, it is imperative that the maternal body can
      increase energy stores without restraint. Food intake, fat mass and serum leptin
      concentrations increase during pregnancy in the rat, suggesting that the feedback
      loop between adipose tissue and appetite is disrupted and a state of leptin
      resistance exists. In support of this, there is an attenuation of the satiety
      response to exogenous leptin administration in pregnant rats. This state of
      leptin resistance is associated with impaired activation of the leptin-induced
      Janus activating kinase (JAK)/signal transducer and activator of transcription
      (STAT) signalling pathway in the ventromedial nucleus of the hypothalamus (VMH)
      and arcuate nucleus, and reduced expression of leptin receptor mRNA in the VMH.
      Furthermore, pregnant rats do not show a satiety response to exogenous alpha
      melanocyte stimulating hormone. This model offers the possibility of examining
      how hypothalamic leptin signalling can be modified in response to changes in
      physiological conditions.

PMID- 18034870
TI  - Diversity in fibroblast growth factor receptor 1 regulation: learning from the
      investigation of Kallmann syndrome.
AB  - The unravelling of the genetic basis of the hypogonadotrophic hypogonadal
      disorders, including Kallmann syndrome (KS), has led to renewed interest into the
      developmental biology of gonadotrophin-releasing hormone (GnRH) neurones and,
      more generally, into the molecular mechanisms of reproduction. KS is
      characterised by the association of GnRH deficiency with diminished olfaction.
      Until recently, only two KS-associated genes were known: KAL1 and KAL2. KAL1
      encodes the cell membrane and extracellular matrix-associated secreted protein
      anosmin-1 which is implicated in the X-linked form of KS. Anosmin-1 shows high
      affinity binding to heparan sulphate (HS) and its function remains the focus of
      ongoing investigation, although a role in axonal guidance and neuronal migration,
      which are processes essential for normal GnRH ontogeny and olfactory bulb
      histogenesis, has been suggested. KAL2, identified as the fibroblast growth
      factor receptor 1 (FGFR1) gene, has now been recognised to be the underlying
      genetic defect for an autosomal dominant form of KS. The diverse signalling
      pathways initiated upon FGFR activation can elicit pleiotropic cellular responses
      depending on the cellular context. Signalling through FGFR requires HS for
      receptor dimerisation and ligand binding. Current evidence supports a HS
      dependent interaction between anosmin-1 and FGFR1, where anosmin-1 serves as a co
      ligand activator enhancing the signal activity, the finer details of whose
      mechanism remain the subject of intense investigation. Recently, mutations in the
      genes encoding prokineticin 2 (PK2) and prokineticin receptor 2 (PKR2) were
      reported in a cohort of KS patients, further reinforcing the view of KS as a
      multigenic trait involving divergent pathways. Here, we review the historical and
      current understandings of KS and discuss the latest findings from the molecular
      and cellular studies of the KS-associated proteins, and describe the evidence
      that suggests convergence of several of these pathways during normal GnRH and
      olfactory neuronal ontogeny.

PMID- 18034871
TI  - The internal initiation of translation in bovine viral diarrhea virus RNA depends
      on the presence of an RNA pseudoknot upstream of the initiation codon.
AB  - BACKGROUND: Bovine viral diarrhea virus (BVDV) is the prototype representative of
      the pestivirus genus in the Flaviviridae family. It has been shown that the
      initiation of translation of BVDV RNA occurs by an internal ribosome entry
      mechanism mediated by the 5' untranslated region of the viral RNA 1. The 5' and
      3' boundaries of the IRES of the cytopathic BVDV NADL have been mapped and it has
      been suggested that the IRES extends into the coding of the BVDV polyprotein 2. A
      putative pseudoknot structure has been recognized in the BVDV 5'UTR in close
      proximity to the AUG start codon. A pseudoknot structure is characteristic for
      flavivirus IRESes and in the case of the closely related classical swine fever
      virus (CSFV) and the more distantly related Hepatitis C virus (HCV) pseudoknot
      function in translation has been demonstrated. RESULTS: To characterize the BVDV
      IRESes in detail, we studied the BVDV translational initiation by transfection of
      dicistronic expression plasmids into mammalian cells. A region coding for the
      amino terminus of the BVDV SD-1 polyprotein contributes considerably to efficient
      initiation of translation. The translation efficiency mediated by the IRES of
      BVDV strains NADL and SD-1 approximates the poliovirus type I IRES directed
      translation in BHK cells. Compared to the poliovirus IRES increased expression
      levels are mediated by the BVDV IRES of strain SD-1 in murine cell lines, while
      lower levels are observed in human cell lines. Site directed mutagenesis revealed
      that a RNA pseudoknot upstream of the initiator AUG is an important structural
      element for IRES function. Mutants with impaired ability to base pair in stem I
      or II lost their translational activity. In mutants with repaired base pairing
      either in stem 1 or in stem 2 full translational activity was restored. Thus, the
      BVDV IRES translation is dependent on the pseudoknot integrity. These features of
      the pestivirus IRES are reminiscent of those of the classical swine fever virus,
      a pestivirus, and the hepatitis C viruses, another genus of the Flaviviridae.
      CONCLUSION: The IRES of the non-cytopathic BVDV SD-1 strain displays features
      known from other pestivirus IRESes. The predicted pseudoknot in the 5'UTR of BVDV
      SD-1 virus represents an important structural element in BVDV translation.

PMID- 18034873
TI  - A comparative analysis of predictive models of morbidity in intensive care unit
      after cardiac surgery - part II: an illustrative example.
AB  - BACKGROUND: Popular predictive models for estimating morbidity probability after
      heart surgery are compared critically in a unitary framework. The study is
      divided into two parts. In the first part modelling techniques and intrinsic
      strengths and weaknesses of different approaches were discussed from a
      theoretical point of view. In this second part the performances of the same
      models are evaluated in an illustrative example. METHODS: Eight models were
      developed: Bayes linear and quadratic models, k-nearest neighbour model, logistic
      regression model, Higgins and direct scoring systems and two feed-forward
      artificial neural networks with one and two layers. Cardiovascular, respiratory,
      neurological, renal, infectious and hemorrhagic complications were defined as
      morbidity. Training and testing sets each of 545 cases were used. The optimal set
      of predictors was chosen among a collection of 78 preoperative, intraoperative
      and postoperative variables by a stepwise procedure. Discrimination and
      calibration were evaluated by the area under the receiver operating
      characteristic curve and Hosmer-Lemeshow goodness-of-fit test, respectively.
      RESULTS: Scoring systems and the logistic regression model required the largest
      set of predictors, while Bayesian and k-nearest neighbour models were much more
      parsimonious. In testing data, all models showed acceptable discrimination
      capacities, however the Bayes quadratic model, using only three predictors,
      provided the best performance. All models showed satisfactory generalization
      ability: again the Bayes quadratic model exhibited the best generalization, while
      artificial neural networks and scoring systems gave the worst results. Finally,
      poor calibration was obtained when using scoring systems, k-nearest neighbour
      model and artificial neural networks, while Bayes (after recalibration) and
      logistic regression models gave adequate results. CONCLUSION: Although all the
      predictive models showed acceptable discrimination performance in the example
      considered, the Bayes and logistic regression models seemed better than the
      others, because they also had good generalization and calibration. The Bayes
      quadratic model seemed to be a convincing alternative to the much more usual
      Bayes linear and logistic regression models. It showed its capacity to identify a
      minimum core of predictors generally recognized as essential to pragmatically
      evaluate the risk of developing morbidity after heart surgery.

PMID- 18034872
TI  - A comparative analysis of predictive models of morbidity in intensive care unit
      after cardiac surgery - part I: model planning.
AB  - BACKGROUND: Different methods have recently been proposed for predicting
      morbidity in intensive care units (ICU). The aim of the present study was to
      critically review a number of approaches for developing models capable of
      estimating the probability of morbidity in ICU after heart surgery. The study is
      divided into two parts. In this first part, popular models used to estimate the
      probability of class membership are grouped into distinct categories according to
      their underlying mathematical principles. Modelling techniques and intrinsic
      strengths and weaknesses of each model are analysed and discussed from a
      theoretical point of view, in consideration of clinical applications. METHODS:
      Models based on Bayes rule, k-nearest neighbour algorithm, logistic regression,
      scoring systems and artificial neural networks are investigated. Key issues for
      model design are described. The mathematical treatment of some aspects of model
      structure is also included for readers interested in developing models, though a
      full understanding of mathematical relationships is not necessary if the reader
      is only interested in perceiving the practical meaning of model assumptions,
      weaknesses and strengths from a user point of view. RESULTS: Scoring systems are
      very attractive due to their simplicity of use, although this may undermine their
      predictive capacity. Logistic regression models are trustworthy tools, although
      they suffer from the principal limitations of most regression procedures.
      Bayesian models seem to be a good compromise between complexity and predictive
      performance, but model recalibration is generally necessary. k-nearest neighbour
      may be a valid non parametric technique, though computational cost and the need
      for large data storage are major weaknesses of this approach. Artificial neural
      networks have intrinsic advantages with respect to common statistical models,
      though the training process may be problematical. CONCLUSION: Knowledge of model
      assumptions and the theoretical strengths and weaknesses of different approaches
      are fundamental for designing models for estimating the probability of morbidity
      after heart surgery. However, a rational choice also requires evaluation and
      comparison of actual performances of locally-developed competitive models in the
      clinical scenario to obtain satisfactory agreement between local needs and model
      response. In the second part of this study the above predictive models will
      therefore be tested on real data acquired in a specialized ICU.

PMID- 18034874
TI  - Inorganic pyrophosphate generation by transforming growth factor-beta-1 is mainly
      dependent on ANK induction by Ras/Raf-1/extracellular signal-regulated kinase
      pathways in chondrocytes.
AB  - ANK is a multipass transmembrane protein transporter thought to play a role in
      the export of intracellular inorganic pyrophosphate and so to contribute to the
      pathophysiology of chondrocalcinosis. As transforming growth factor-beta-1 (TGF
      beta1) was shown to favor calcium pyrophosphate dihydrate deposition, we
      investigated the contribution of ANK to the production of extracellular inorganic
      pyrophosphate (ePPi) by chondrocytes and the signaling pathways involved in the
      regulation of Ank expression by TGF-beta1. Chondrocytes were exposed to 10 ng/mL
      of TGF-beta1, and Ank expression was measured by quantitative polymerase chain
      reaction and Western blot. ePPi was quantified in cell supernatants. RNA
      silencing was used to define the respective roles of Ank and PC-1 in TGF-beta1
      induced ePPi generation. Finally, selective kinase inhibitors and dominant
      negative/overexpression plasmid strategies were used to explore the contribution
      of several signaling pathways to Ank induction by TGF-beta1. TGF-beta1 strongly
      increased Ank expression at the mRNA and protein levels, as well as ePPi
      production. Using small interfering RNA technology, we showed that Ank
      contributed approximately 60% and PC-1 nearly 20% to TGF-beta1-induced ePPi
      generation. Induction of Ank by TGF-beta1 required activation of the
      extracellular signal-regulated kinase (ERK) pathway but not of p38-mitogen
      activated protein kinase or of protein kinase A. In line with the general protein
      kinase C (PKC) inhibitor calphostin C, Go6976 (a Ca2+-dependent PKC inhibitor)
      diminished TGF-beta1-induced Ank expression by 60%, whereas a 10% inhibition was
      observed with rottlerin (a PKCdelta inhibitor). These data suggest a regulatory
      role for calcium in TGF-beta1-induced Ank expression. Finally, we demonstrated
      that the stimulatory effect of TGF-beta1 on Ank expression was inhibited by the
      suppression of the Ras/Raf-1 pathway, while being enhanced by their constitutive
      activation. Transient overexpression of Smad 7, an inhibitory Smad, failed to
      affect the inducing effect of TGF-beta1 on Ank mRNA level. These data show that
      TGF-beta1 increases ePPi levels, mainly by the induction of the Ank gene, which
      requires activation of Ras, Raf-1, ERK, and Ca2+-dependent PKC pathways in
      chondrocytes.

PMID- 18034875
TI  - Genome-wide transcriptional analysis of grapevine berry ripening reveals a set of
      genes similarly modulated during three seasons and the occurrence of an oxidative
      burst at veraison.
AB  - BACKGROUND: Grapevine (Vitis species) is among the most important fruit crops in
      terms of cultivated area and economic impact. Despite this relevance, little is
      known about the transcriptional changes and the regulatory circuits underlying
      the biochemical and physical changes occurring during berry development. RESULTS:
      Fruit ripening in the non-climacteric crop species Vitis vinifera L. has been
      investigated at the transcriptional level by the use of the Affymetrix Vitis
      GeneChip which contains approximately 14,500 unigenes. Gene expression data
      obtained from berries sampled before and after veraison in three growing years,
      were analyzed to identify genes specifically involved in fruit ripening and to
      investigate seasonal influences on the process. From these analyses a core set of
      1477 genes was found which was similarly modulated in all seasons. We were able
      to separate ripening specific isoforms within gene families and to identify
      ripening related genes which appeared strongly regulated also by the seasonal
      weather conditions. Transcripts annotation by Gene Ontology vocabulary revealed
      five overrepresented functional categories of which cell wall organization and
      biogenesis, carbohydrate and secondary metabolisms and stress response were
      specifically induced during the ripening phase, while photosynthesis was strongly
      repressed. About 19% of the core gene set was characterized by genes involved in
      regulatory processes, such as transcription factors and transcripts related to
      hormonal metabolism and signal transduction. Auxin, ethylene and light emerged as
      the main stimuli influencing berry development. In addition, an oxidative burst,
      previously not detected in grapevine, characterized by rapid accumulation of H2O2
      starting from veraison and by the modulation of many ROS scavenging enzymes, was
      observed. CONCLUSION: The time-course gene expression analysis of grapevine berry
      development has identified the occurrence of two well distinct phases along the
      process. The pre-veraison phase represents a reprogramming stage of the cellular
      metabolism, characterized by the expression of numerous genes involved in
      hormonal signalling and transcriptional regulation. The post-veraison phase is
      characterized by the onset of a ripening-specialized metabolism responsible for
      the phenotypic traits of the ripe berry. Between the two phases, at veraison, an
      oxidative burst and the concurrent modulation of the anti-oxidative enzymatic
      network was observed. The large number of regulatory genes we have identified
      represents a powerful new resource for dissecting the mechanisms of fruit
      ripening control in non-climacteric plants.

PMID- 18034877
TI  - Missed opportunities for participation in prevention of mother to child
      transmission programmes: simplicity of nevirapine does not necessarily lead to
      optimal uptake, a qualitative study.
AB  - BACKGROUND: The objective of this study was to examine missed opportunities for
      participation in a prevention of mother-to-child transmission (PMTCT) programme
      in three sites in South Africa. A rapid anthropological assessment was used to
      collect in-depth data from 58 HIV-positive women who were enrolled in a larger
      cohort study to assess mother-to-child HIV transmission. Semi-structured
      interviews were conducted with the women in order to gain an understanding of
      their experiences of antenatal care and to identify missed opportunities for
      participation in PMTCT. RESULTS: 15 women actually missed their nevirapine not
      because of stigma and ignorance but because of health systems failures. Six were
      not tested for HIV during antenatal care. Two were tested but did not receive
      their results. Seven were tested and received their results, but did not receive
      nevirapine. Health Systems failure for these programme leakages ranged from non
      availability of counselors, supplies such as HIV test kits, consent forms, health
      staff giving the women incorrect instructions about when to take the tablet and
      health staff not supplying the women with the tablet to take. CONCLUSION: HIV
      testing enables access to PMTCT interventions and should therefore be
      strengthened. The single dose nevirapine regimen is simple to implement but the
      all or nothing nature of the regimen may result in many missed opportunities. A
      short course dual or triple drug regimen could increase the effectiveness of
      PMTCT programmes.

PMID- 18034876
TI  - Transcriptomic and metabolite analyses of Cabernet Sauvignon grape berry
      development.
AB  - BACKGROUND: Grape berry development is a dynamic process that involves a complex
      series of molecular genetic and biochemical changes divided into three major
      phases. During initial berry growth (Phase I), berry size increases along a
      sigmoidal growth curve due to cell division and subsequent cell expansion, and
      organic acids (mainly malate and tartrate), tannins, and hydroxycinnamates
      accumulate to peak levels. The second major phase (Phase II) is defined as a lag
      phase in which cell expansion ceases and sugars begin to accumulate. Veraison
      (the onset of ripening) marks the beginning of the third major phase (Phase III)
      in which berries undergo a second period of sigmoidal growth due to additional
      mesocarp cell expansion, accumulation of anthocyanin pigments for berry color,
      accumulation of volatile compounds for aroma, softening, peak accumulation of
      sugars (mainly glucose and fructose), and a decline in organic acid accumulation.
      In order to understand the transcriptional network responsible for controlling
      berry development, mRNA expression profiling was conducted on berries of V.
      vinifera Cabernet Sauvignon using the Affymetrix GeneChip Vitis oligonucleotide
      microarray ver. 1.0 spanning seven stages of berry development from small pea
      size berries (E-L stages 31 to 33 as defined by the modified E-L system), through
      veraison (E-L stages 34 and 35), to mature berries (E-L stages 36 and 38).
      Selected metabolites were profiled in parallel with mRNA expression profiling to
      understand the effect of transcriptional regulatory processes on specific
      metabolite production that ultimately influence the organoleptic properties of
      wine. RESULTS: Over the course of berry development whole fruit tissues were
      found to express an average of 74.5% of probes represented on the Vitis
      microarray, which has 14,470 Unigenes. Approximately 60% of the expressed
      transcripts were differentially expressed between at least two out of the seven
      stages of berry development (28% of transcripts, 4,151 Unigenes, had pronounced
      (> or =2 fold) differences in mRNA expression) illustrating the dynamic nature of
      the developmental process. The subset of 4,151 Unigenes was split into twenty
      well-correlated expression profiles. Expression profile patterns included those
      with declining or increasing mRNA expression over the course of berry development
      as well as transient peak or trough patterns across various developmental stages
      as defined by the modified E-L system. These detailed surveys revealed the
      expression patterns for genes that play key functional roles in phytohormone
      biosynthesis and response, calcium sequestration, transport and signaling, cell
      wall metabolism mediating expansion, ripening, and softening, flavonoid
      metabolism and transport, organic and amino acid metabolism, hexose sugar and
      triose phosphate metabolism and transport, starch metabolism, photosynthesis,
      circadian cycles and pathogen resistance. In particular, mRNA expression patterns
      of transcription factors, abscisic acid (ABA) biosynthesis, and calcium signaling
      genes identified candidate factors likely to participate in the progression of
      key developmental events such as veraison and potential candidate genes
      associated with such processes as auxin partitioning within berry cells, aroma
      compound production, and pathway regulation and sequestration of flavonoid
      compounds. Finally, analysis of sugar metabolism gene expression patterns
      indicated the existence of an alternative pathway for glucose and triose
      phosphate production that is invoked from veraison to mature berries. CONCLUSION:
      These results reveal the first high-resolution picture of the transcriptome
      dynamics that occur during seven stages of grape berry development. This work
      also establishes an extensive catalog of gene expression patterns for future
      investigations aimed at the dissection of the transcriptional regulatory
      hierarchies that govern berry development in a widely grown cultivar of wine
      grape. More importantly, this analysis identified a set of previously unknown
      genes potentially involved in critical steps associated with fruit development
      that can now be subjected to functional testing.

PMID- 18034878
TI  - Prevalence of cataract in adult Down's syndrome patients aged 28 to 83 years.
AB  - BACKGROUND: Age-related cataract is the major cause of blindness in humans
      throughout the world. The majority of previous studies of cataract in Down's
      syndrome (which usually results from trisomy 21) have reported that the
      prevalence of this ocular abnormality is higher for a given age range than in the
      general population. The objective of the present study was to study the
      prevalence of cataract in a well-defined population of adults with Down's
      syndrome. METHODS: An in-patient population of 68 adults (35 males and 33
      females) with Down's syndrome, aged between 28.9 and 83.3 years, underwent
      ophthalmological examination for the presence of cataracts. RESULTS: Overall, the
      prevalence of cataract was 16.2%, with no significant difference in the
      prevalence between males (17.1%) and females (15.2%). In those aged between 45
      and 64 years, the prevalence was 16.7%, rising in those aged between 65 and 75
      years to 28.6%. CONCLUSION: Compared with the general population, the prevalence
      of cataract in Down's syndrome was raised in those aged 45 to 64, but not in
      those aged 65 to 75 years; the latter might be a function of the relatively small
      number of patients in this age group. The increased prevalence of cataract found
      in those in the 45- to 64-year-old age group may be the result of increased
      levels of the copper- and zinc-containing superoxide dismutase enzyme (CuZnSOD),
      in turn resulting from the location of the associated five exons of SOD1 on
      chromosome 21. These elevated levels of superoxide dismutase may give rise to
      increased levels of reactive species, including hydrogen peroxide and hydroxyl
      radicals, which may increase the risk of cataractogenesis. It is suggested that
      nutritional supplementation with antioxidants may therefore help reduce the
      prevalence of cataract in Down's syndrome.

PMID- 18034879
TI  - International Web-based consultation on priorities for translational breast
      cancer research.
AB  - BACKGROUND: Large numbers of translational breast cancer research topics have
      been completed or are underway, but they differ widely in their immediate and/or
      future importance to clinical management. We therefore conducted an international
      Web-based consultation of breast cancer professionals to identify the topics most
      widely considered to be of highest priority. METHODS: Potential participants were
      contacted via two large e-mail databases and asked to register, at a Web site,
      the issues that they felt to be of highest priority. Four hundred nine questions
      were reduced by a steering committee to 70 unique issues, and registrants were
      asked to select the 6 questions they considered to be the most important.
      RESULTS: Votes were recorded from 420 voters (2,520 votes) from 48 countries,
      with 48% of voters coming from North America. Half of the voters identified
      themselves as clinicians, with the remainder being academics, research
      scientists, or pathologists. The highest priority was to identify molecular
      signatures to select patients who could be spared chemotherapy, which gained
      about 50% more votes than the second topic and was consistently voted top by
      voters in North America, Europe, and the rest of the world. Research scientists
      voted the determination of the role of stem cells in breast cancer development,
      progression, and treatment sensitivity as the most important issue, but this was
      considered the sixth priority for clinicians and fourth overall. CONCLUSION: This
      exercise may bring a greater focus of research resources onto issues voted as top
      priorities.

PMID- 18034880
TI  - Altered retinal microRNA expression profile in a mouse model of retinitis
      pigmentosa.
AB  - BACKGROUND: The role played by microRNAs (miRs) as common regulators in
      physiologic processes such as development and various disease states was recently
      highlighted. Retinitis pigmentosa (RP) linked to RHO (which encodes rhodopsin) is
      the most frequent form of inherited retinal degeneration that leads to blindness,
      for which there are no current therapies. Little is known about the cellular
      mechanisms that connect mutations within RHO to eventual photoreceptor cell death
      by apoptosis. RESULTS: Global miR expression profiling using miR microarray
      technology and quantitative real-time RT-PCR (qPCR) was performed in mouse
      retinas. RNA samples from retina of a mouse model of RP carrying a mutant
      Pro347Ser RHO transgene and from wild-type retina, brain and a whole-body
      representation (prepared by pooling total RNA from eight different mouse organs)
      exhibited notably different miR profiles. Expression of retina-specific and
      recently described retinal miRs was semi-quantitatively demonstrated in wild-type
      mouse retina. Alterations greater than twofold were found in the expression of
      nine miRs in Pro347Ser as compared with wild-type retina (P < 0.05). Expression
      of miR-1 and miR-133 decreased by more than 2.5-fold (P < 0.001), whereas
      expression of miR-96 and miR-183 increased by more than 3-fold (P < 0.001) in
      Pro347Ser retinas, as validated by qPCR. Potential retinal targets for these miRs
      were predicted in silico. CONCLUSION: This is the first miR microarray study to
      focus on evaluating altered miR expression in retinal disease. Additionally,
      novel retinal preference for miR-376a and miR-691 was identified. The results
      obtained contribute toward elucidating the function of miRs in normal and
      diseased retina. Modulation of expression of retinal miRs may represent a future
      therapeutic strategy for retinopathies such as RP.

PMID- 18034881
TI  - Cost-effectiveness of tipranavir versus comparator protease inhibitor regimens in
      HIV infected patients previously exposed to antiretroviral therapy in the
      Netherlands.
AB  - BACKGROUND: This study compares the costs and effects of a regimen with ritonavir
      boosted tipranavir (TPV/r) to a physician-selected genotypically-defined standard
      of-care comparator protease inhibitor regimen boosted with ritonavir (CPI/r) in
      HIV infected patients that were previously exposed to antiretroviral therapy in
      the Netherlands. METHODS: We compared the projected lifetime costs and effects of
      two theoretical groups of 1000 patients, one receiving a standard of care regimen
      with TPV/r as a component and the other receiving a standard of care regimen with
      CPI/r. A 3-stage Markov model was formulated to represent three different
      consecutive HAART regimens. The model uses 12 health states based on viral load
      and CD4+ count to simulate disease progression. The transition probabilities for
      the Markov model were derived from a United States cohort of treatment
      experienced HIV patients. Furthermore, the study design was based on 48-week data
      from the RESIST-2 clinical trial and local Dutch costing data. Cost and health
      effects were discounted at 4% and 1.5% respectively according to the Dutch
      guideline. The analysis was conducted from the Dutch healthcare perspective using
      2006 unit cost prices. RESULTS: Our model projects an accumulated discounted cost
      to the Dutch healthcare system per patient receiving the TPV/r regimen of
      euro167,200 compared to euro145,400 for the CPI/r regimen. This results in an
      incremental cost of euro21,800 per patient. The accumulated discounted effect is
      7.43 life years or 6.31 quality adjusted life years (QALYs) per patient receiving
      TPV/r, compared to 6.91 life years or 5.80 QALYs per patient receiving CPI/r.
      This translates into an incremental effect of TPV/r over CPI/r of 0.52 life years
      gained (LYG) or 0.51 QALYs gained. The corresponding incremental cost
      effectiveness ratios (iCERs) are euro41,600 per LYG and euro42,500 per QALY.
      CONCLUSION: We estimated the iCER for TPV/r compared to CPI/r at approximately
      euro40,000 in treatment experienced HIV-1 infected patients in the Netherlands.
      This ratio may well be in range of what is acceptable and warrants reimbursement
      for new drug treatments in the Netherlands, in particular in therapeutic areas as
      end-stage oncology and HIV and other last-resort health-care interventions.

PMID- 18034882
TI  - Participation in environmental health research by placenta donation - a
      perception study.
AB  - BACKGROUND: Much environmental health research depends on human volunteers
      participating with biological samples. The perception study explores why and how
      people participate in a placenta perfusion study in Copenhagen. The participation
      implies donation of the placenta after birth and some background information but
      no follow up. METHODS: Nineteen semi-structured qualitative interviews were
      conducted with participants in the placenta perfusion study after donation of
      placenta. Observation studies were made of recruitment sessions. RESULTS: The
      interviewed participants are generally in favour of medical research. They
      participated in the placenta perfusion study due to a belief that societal
      progress follows medical research. They also felt that participating was a way of
      giving something back to the Danish health care system. The participants have
      trust in medical science and scientists, but trust is something which needs to be
      created through "trust-work". Face-to-face interaction, written information
      material and informed consent forms play important parts in creating trusting
      relationships in medical research. CONCLUSION: Medical research ethics do not
      only amount to specific types of written information material but should also be
      seen as a number of trust making performances involving researchers as well as
      research participants.

PMID- 18034883
TI  - Outcome of index upper gastrointestinal endoscopy in patients presenting with
      dysphagia in a tertiary care hospital-A 10 years review.
AB  - BACKGROUND: Patients with malignant tumours of the upper gastrointestinal tract
      tumours exhibit important alarm symptoms such as dysphagia that warrant clinical
      investigations. An endoscopic examination of the upper gastrointestinal tract
      will be required in most cases. This study evaluates the diagnostic potential of
      index endoscopy in a random population of patients with dysphagia. METHODS: This
      is a retrospective analysis of prospectively collected data over 10 years.
      Patients with previous endoscopic evaluation or upper gastrointestinal pathology
      were excluded from the study. Data was analysed to see the number and frequency
      of abnormal findings in upper gastrointestinal tract, and their significance in
      relation to the presenting symptoms. RESULTS: Total number of index endoscopies
      was 13, 881. 913 patients were included in the study including 465 males (age
      range: 17-92 years, median: 55 years) and 448 females (age range: 18-100, median:
      59 years), with male to female ratio of 1.04: 1. Oesophagus was abnormal in 678
      cases (74%) and biopsies were taken in 428 patients (47%). Superficial
      oesophagitis, Barrett's oesophagus, oesophageal cancer, and oesophageal ulcer
      were main histological findings. Age more than 50 years and weight loss were
      significant predictors of oesophageal cancer (p < 0.0001). Male gender,
      heartburn, epigastric pain, weight loss and vomiting were significantly related
      to Barrett's oesophagus. A total of 486 gastric and 56 duodenal biopsies were
      also taken. There were 20 cases of gastric adenocarcinoma. CONCLUSION: OGD is an
      effective initial investigation to assess patients with dysphagia, especially
      males above the age of 50 years. Patients may be started on treatment or referred
      for further investigations, for example, a barium meal in the absence of any
      anatomical abnormality.

PMID- 18034884
TI  - Spontaneous corneal melting in pregnancy: a case report.
AB  - BACKGROUND: To report a case of spontaneous corneal melting in pregnancy. We
      reviewed the literature on corneal melting and the effect of pregnancy on cornea
      and collagen containing tissues. CASE PRESENTATION: A 29-year-old woman who
      underwent radial keratotomy in both eyes followed by trabeculectomy in her left
      eye developed corneal melting in the same eye, in her seventh month of pregnancy.
      Despite screening, no infectious or immune mediated condition could be
      identified. She was managed conservatively with cyanoacrylate glue, bandage
      contact lens, lubricants and antibiotics. CONCLUSION: It may not always be
      possible to find the underlying cause of corneal melting but the more common
      underlying causes should be ruled out by proper investigations. Pregnancy with
      its host of hormonal changes could potentially have some effect on corneal
      collagen leading to corneal melting in compromised corneas.

PMID- 18034885
TI  - CoryneCenter - an online resource for the integrated analysis of corynebacterial
      genome and transcriptome data.
AB  - BACKGROUND: The introduction of high-throughput genome sequencing and post-genome
      analysis technologies, e.g. DNA microarray approaches, has created the potential
      to unravel and scrutinize complex gene-regulatory networks on a large scale. The
      discovery of transcriptional regulatory interactions has become a major topic in
      modern functional genomics. RESULTS: To facilitate the analysis of gene
      regulatory networks, we have developed CoryneCenter, a web-based resource for the
      systematic integration and analysis of genome, transcriptome, and gene regulatory
      information for prokaryotes, especially corynebacteria. For this purpose, we
      extended and combined the following systems into a common platform: (1) GenDB, an
      open source genome annotation system, (2) EMMA, a MAGE compliant application for
      high-throughput transcriptome data storage and analysis, and (3) CoryneRegNet, an
      ontology-based data warehouse designed to facilitate the reconstruction and
      analysis of gene regulatory interactions. We demonstrate the potential of
      CoryneCenter by means of an application example. Using microarray hybridization
      data, we compare the gene expression of Corynebacterium glutamicum under acetate
      and glucose feeding conditions: Known regulatory networks are confirmed, but
      moreover CoryneCenter points out additional regulatory interactions. CONCLUSION:
      CoryneCenter provides more than the sum of its parts. Its novel analysis and
      visualization features significantly simplify the process of obtaining new
      biological insights into complex regulatory systems. Although the platform
      currently focusses on corynebacteria, the integrated tools are by no means
      restricted to these species, and the presented approach offers a general strategy
      for the analysis and verification of gene regulatory networks. CoryneCenter
      provides freely accessible projects with the underlying genome annotation, gene
      expression, and gene regulation data. The system is publicly available at
      http://www.CoryneCenter.de.

PMID- 18034886
TI  - Mechanisms of Legionella pneumophila-induced interleukin-8 expression in human
      lung epithelial cells.
AB  - BACKGROUND: Legionella pneumophila is a facultative intracellular bacterium,
      capable of replicating within the phagosomes of macrophages and monocytes, but
      little is known about its interaction with human lung epithelial cells. We
      investigated the effect of L. pneumophila on the expression of interleukin-8 (IL
      8) in human A549 alveolar and NCI-H292 tracheal epithelial cell lines. RESULTS:
      Infection of L. pneumophila strain, but not heat-killed strain, resulted in
      upregulation of IL-8. IL-8 mRNA expression was induced immediately after the
      infection and its signal became gradually stronger until 24 h after infection. On
      the other hand, IL-8 expression in A549 cells infected with L. pneumophila
      lacking a functional type IV secretion system was transient. The IL-8 expression
      was slightly induced at 16 h and increased at 24 h after infection with flagellin
      deficient Legionella. Activation of the IL-8 promoter by L. pneumophila infection
      occurred through the action of nuclear factor-kappaB (NF-kappaB). Transfection of
      dominant negative mutants of NF-kappaB-inducing kinase, IkappaB kinase and
      IkappaB inhibited L. pneumophila-mediated activation of IL-8 promoter. Treatment
      with hsp90 inhibitor suppressed L. pneumophila-induced IL-8 mRNA due to
      deactivation of NF-kappaB. CONCLUSION: Collectively, these results suggest that
      L. pneumophila induces activation of NF-kappaB through an intracellular signaling
      pathway that involves NF-kappaB-inducing kinase and IkappaB kinase, leading to IL
      8 gene transcription, and that hsp90 acts as a crucial regulator in L.
      pneumophila-induced IL-8 expression, presumably contributing to immune response
      in L. pneumophila. The presence of flagellin and a type IV secretion system are
      critical for Legionella to induce IL-8 expression in lung epithelial cells.

PMID- 18034887
TI  - Identification of the main malaria vectors in the Anopheles gambiae species
      complex using a TaqMan real-time PCR assay.
AB  - BACKGROUND: The Anopheles gambiae sensu lato species complex comprises seven
      sibling species of mosquitoes that are morphologically indistinguishable. Rapid
      identification of the two main species which vector malaria, Anopheles arabiensis
      and An. gambiae sensu stricto, from the non-vector species Anopheles
      quadriannulatus is often required as part of vector control programmes. Currently
      the most widely used method for species identification is a multiplex PCR
      protocol that targets species specific differences in ribosomal DNA sequences.
      While this assay has proved to be reasonably robust in many studies, additional
      steps are required post-PCR making it time consuming. Recently, a high-throughput
      assay based on TaqMan single nucleotide polymorphism genotyping that detects and
      discriminates An. gambiae s.s and An. arabiensis has been reported. METHODS: A
      new TaqMan assay was developed that distinguishes between the main malaria
      vectors (An. arabiensis and An. gambiae s.s.) and the non-vector An.
      quadriannulatus after it was found that the existing TaqMan assay incorrectly
      identified An. quadriannulatus, An. merus and An. melas as An. gambiae s.s. The
      performance of this new TaqMan assay was compared against the existing TaqMan
      assay and the standard PCR method in a blind species identification trial of over
      450 samples using field collected specimens from a total of 13 countries in Sub
      Saharan Africa. RESULTS: The standard PCR method was found to be specific with a
      low number of incorrect scores (<1%), however when compared to the TaqMan assays
      it showed a significantly higher number of failed reactions (15%). Both the new
      vector-specific TaqMan assay and the exisiting TaqMan showed a very low number of
      incorrectly identified samples (0 and 0.54%) and failed reactions (1.25% and
      2.96%). In tests of analytical sensitivity the new TaqMan assay showed a very low
      detection threshold and can consequently be used on a single leg from a fresh or
      silica-dried mosquito without the need to first extract DNA. CONCLUSION: This
      study describes a rapid and sensitive assay that very effectively identifies the
      two main malaria vectors of the An. gambiae species complex from the non-vector
      sibling species. The method is based on TaqMan SNP genotyping and can be used to
      screen single legs from dried specimens. In regions where An.
      merus/melas/bwambae, vectors with restricted distributions, are not present it
      can be used alone to discriminate vector from non-vector or in combination with
      the Walker TaqMan assay to distinguish An. arabiensis and An. gambiae s.s.

PMID- 18034888
TI  - Prediction of volume response under open-chest conditions during coronary artery
      bypass surgery.
AB  - INTRODUCTION: Adequate fluid loading is the first step of hemodynamic
      optimization in cardiac patients undergoing surgery. Neither a clinical approach
      alone nor conventional parameters like central venous pressure (CVP) and
      pulmonary capillary wedge pressure (PCWP) are thought to be sufficient for
      recognizing fluid deficiency or overload. The aim of this study was to evaluate
      the suitability of CVP, PCWP, global end-diastolic volume index (GEDVI), pulse
      pressure variation (PPV), and stroke volume variation (SVV) for predicting
      changes in the cardiac index (CI) and stroke volume index (SVI) after sternotomy.
      METHODS: In 40 patients, CVP, PCWP, GEDVI, PPV, SVV, and the CI were measured at
      two points of time. One measurement was performed after inducing anesthesia and
      one after sternotomy. RESULTS: A significant increase in heart rate, CI, and
      GEDVI was observed during the study period. CVP, SVV, and PPV decreased
      significantly. There were no significant correlations between CVP and PCWP and
      changes in CI. In contrast, GEDVI, SVV, and PPV significantly correlated with CI
      changes. Only relative changes of GEDVI, SVV, and PPV predicted changes in SVI.
      CONCLUSION: During cardiac surgery and especially after sternotomy, CVP and PCWP
      are not suitable for monitoring fluid status. Direct volume measurement like
      GEDVI and dynamic volume responsive measurements like SVV and PPV may be more
      suitable for monitoring the volume status of patients, particularly under open
      chest conditions.

PMID- 18034889
TI  - Structural analysis of the carboxy terminal PH domain of pleckstrin bound to D
      myo-inositol 1,2,3,5,6-pentakisphosphate.
AB  - BACKGROUND: Pleckstrin homology (PH) domains are one of the most prevalent
      domains in the human proteome and represent the major phosphoinositide-binding
      module. These domains are often found in signaling proteins and function
      predominately by targeting their host proteins to the cell membrane. Inositol
      phosphates, which are structurally similar to phosphoinositides, are not only
      known to play a role as signaling molecules but are also capable of being bound
      by PH domains. RESULTS: In the work presented here it is shown that the addition
      of commercial myo-inositol hexakisphosphate (IP6) inhibited the binding of the
      carboxy terminal PH domain of pleckstrin (C-PH) to phosphatidylinositol 3,4
      bisphosphate with an IC50 of 7.5 muM. In an attempt to characterize this binding
      structurally, C-PH was crystallized in the presence of IP6 and the structure was
      determined to 1.35 A. Examination of the resulting electron density unexpectedly
      revealed the bound ligand to be D-myo-inositol 1,2,3,5,6-pentakisphosphate.
      CONCLUSION: The discovery of D-myo-inositol 1,2,3,5,6-pentakisphosphate in the
      crystal structure suggests that the inhibitory effects observed in the binding
      studies may be due to this ligand rather than IP6. Analysis of the protein-ligand
      interaction demonstrated that this myo-inositol pentakisphosphate isomer
      interacts specifically with protein residues known to be involved in
      phosphoinositide binding. In addition to this, a structural alignment of other PH
      domains bound to inositol phosphates containing either four or five phosphate
      groups revealed that the majority of phosphate groups occupy conserved locations
      in the binding pockets of PH domains. These findings, taken together with other
      recently reported studies suggest that myo-inositol pentakisphosphates could act
      to regulate PH domain-phosphoinositide interactions by directly competing for
      binding, thus playing an important role as signaling molecules.

PMID- 18034890
TI  - Procalcitonin (PCT) and C-reactive protein (CRP) as severe systemic infection
      markers in febrile neutropenic adults.
AB  - BACKGROUND: Procalcitonin (PCT) is an inflammatory marker that has been used as
      indicator of severe bacterial infection. We evaluated the concentrations of PCT
      as a marker for systemic infection compared to C-reactive protein (CRP) in
      patients neutropenic febrile. METHODS: 52 adult patients were enrolled in the
      study. Blood sample was collected in order to determine the serum concentrations
      of PCT, CRP and other hematological parameters at the onset of fever. The
      patients were divided into 2 groups, one with severe infection (n = 26) and the
      other in which the patients did not present such an infection (n = 26). Then PCT
      and CRP concentrations at the fever onset were compared between groups using non
      parametric statistical tests, ROC curve, sensitivity, specificity, likelihood
      ratio, and Spearman's correlation coefficient. RESULTS: The mean of PCT was
      significantly higher in the group with severe infection (6.7 ng/mL versus 0.6
      ng/mL - p = 0.0075) comparing with CRP. Serum concentrations of 0.245 ng/mL of
      PCT displayed 100% de sensitivity and 69.2% specificity. PCT concentrations of
      2,145 ng/mL presented a likelihood ratio of 13, which was not observed for any
      concentration of CRP. CONCLUSION: PCT seems to be an useful marker for the
      diagnosis of systemic infection in febrile neutropenic patients, probably better
      than CRP.

PMID- 18034891
TI  - Dendroscope: An interactive viewer for large phylogenetic trees.
AB  - BACKGROUND: Research in evolution requires software for visualizing and editing
      phylogenetic trees, for increasingly very large datasets, such as arise in
      expression analysis or metagenomics, for example. It would be desirable to have a
      program that provides these services in an efficient and user-friendly way, and
      that can be easily installed and run on all major operating systems. Although a
      large number of tree visualization tools are freely available, some as a part of
      more comprehensive analysis packages, all have drawbacks in one or more domains.
      They either lack some of the standard tree visualization techniques or basic
      graphics and editing features, or they are restricted to small trees containing
      only tens of thousands of taxa. Moreover, many programs are difficult to install
      or are not available for all common operating systems. RESULTS: We have developed
      a new program, Dendroscope, for the interactive visualization and navigation of
      phylogenetic trees. The program provides all standard tree visualizations and is
      optimized to run interactively on trees containing hundreds of thousands of taxa.
      The program provides tree editing and graphics export capabilities. To support
      the inspection of large trees, Dendroscope offers a magnification tool. The
      software is written in Java 1.4 and installers are provided for Linux/Unix, MacOS
      X and Windows XP. CONCLUSION: Dendroscope is a user-friendly program for
      visualizing and navigating phylogenetic trees, for both small and large datasets.

PMID- 18034892
TI  - Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549
      cells.
AB  - BACKGROUND: The studies on cancer-stem-cells (CSCs) have attracted so much
      attention in recent years as possible therapeutic implications. This study was
      carried out to investigate the gene expression profile of CSCs in human lung
      adenocarcinoma A549 cells. RESULTS: We isolated CSCs from A549 cell line of which
      side population (SP) phenotype revealed several stem cell properties. After
      staining the cell line with Hoechst 33342 dye, the SP and non-side population
      (non-SP) cells were sorted using flow cytometric analysis. The mRNA expression
      profiles were measured using an Affymetrix GeneChip(R) oligonucleotide array.
      Among the sixty one differentially expressed genes, the twelve genes inclusive
      three poor prognostic genes; Aldo-keto reductase family 1, member C1/C2
      (AKR1C1/C2), Transmembrane 4 L six family member 1 nuclear receptor (TM4SF1), and
      Nuclear receptor subfamily 0, group B, member 1 (NR0B1) were significantly up
      regulated in SP compared to non-SP cells. CONCLUSION: This is the first report
      indicating the differences of gene expression pattern between SP and non-SP cells
      in A549 cells. We suggest that the up-regulations of the genes AKR1C1/C2, TM4SF1
      and NR0B1 in SP of human adenocarcinoma A549 cells could be a target of poor
      prognosis in anti-cancer therapy.

PMID- 18034893
TI  - Nasoendotracheal tube obstruction by a nasal polyp in emergency oral surgery: a
      case report.
AB  - Nasal polyps can make nasoendotracheal intubation difficult. We present a case
      of complete obstruction of a nasoendotracheal tube by a nasal polyp during a
      blind nasoendotracheal intubation in emergency oral surgery.

PMID- 18034895
TI  - Membrane binding of the neuronal calcium sensor recoverin - modulatory role of
      the charged carboxy-terminus.
AB  - BACKGROUND: The Ca2+-binding protein recoverin operates as a Ca2+-sensor in
      vertebrate photoreceptor cells. It undergoes a so-called Ca2+-myristoyl switch
      when cytoplasmic Ca2+-concentrations fluctuate in the cell. Its covalently
      attached myristoyl-group is exposed at high Ca2+-concentrations and enables
      recoverin to associate with lipid bilayers and to inhibit its target rhodopsin
      kinase. At low Ca2+-concentrations the myristoyl group is inserted into a
      hydrophobic pocket of recoverin thereby relieving inhibitory constraint on
      rhodopsin kinase. Hydrophobic and electrostatic interactions of recoverin with
      membranes have not been clearly determined, in particular the function of the
      positively charged carboxy-terminus in recoverin 191QKVKEKLKEKKL202 in this
      context is poorly understood. RESULTS: Binding of myristoylated recoverin to
      lipid bilayer depends on the charge distribution in phospholipids. Binding was
      tested by equilibrium centrifugation and surface plasmon resonance (SPR) assays.
      It is enhanced to a certain degree by the inclusion of phosphatidylserine (up to
      60%) in the lipid mixture. However, a recoverin mutant that lacked the charged
      carboxy-terminus displayed the same relative binding amplitudes as wildtype (WT)
      recoverin when bound to neutral or acidic lipids. Instead, the charged carboxy
      terminus of recoverin has a significant impact on the biphasic dissociation of
      recoverin from membranes. On the other hand, the nonmyristoylated WT and
      truncated mutant form of recoverin did not bind to lipid bilayers to a
      substantial amount as binding amplitudes observed in SPR measurements are similar
      to bulk refractive index changes. CONCLUSION: Our data indicate a small, but
      evident electrostatic contribution to the overall binding energy of recoverin
      association with lipid bilayer. Properties of the charged carboxy-terminus are
      consistent with a role of this region as an internal effector region that
      prolongs the time recoverin stays on the membrane by influencing its Ca2+
      sensitivity.

PMID- 18034894
TI  - A focused antibody library for selecting scFvs expressed at high levels in the
      cytoplasm.
AB  - BACKGROUND: Intrabodies are defined as antibody molecules which are ectopically
      expressed inside the cell. Such intrabodies can be used to visualize or inhibit
      the targeted antigen in living cells. However, most antibody fragments cannot be
      used as intrabodies because they do not fold under the reducing conditions of the
      cell cytosol and nucleus. RESULTS: We describe the construction and validation of
      a large synthetic human single chain antibody fragment library based on a unique
      framework and optimized for cytoplasmic expression. Focusing the library by
      mimicking the natural diversity of CDR3 loops ensured that the scFvs were fully
      human and functional. We show that the library is highly diverse and functional
      since it has been possible to isolate by phage-display several strong binders
      against the five proteins tested in this study, the Syk and Aurora-A protein
      kinases, the alphabeta tubulin dimer, the papillomavirus E6 protein and the core
      histones. Some of the selected scFvs are expressed at an exceptional high level
      in the bacterial cytoplasm, allowing the purification of 1 mg of active scFv from
      only 20 ml of culture. Finally, we show that after three rounds of selection
      against core histones, more than half of the selected scFvs were active when
      expressed in vivo in human cells since they were essentially localized in the
      nucleus. CONCLUSION: This new library is a promising tool not only for an easy
      and large-scale selection of functional intrabodies but also for the isolation of
      highly expressed scFvs that could be used in numerous biotechnological and
      therapeutic applications.

PMID- 18034896
TI  - MADS-complexes regulate transcriptome dynamics during pollen maturation.
AB  - BACKGROUND: Differentiation processes are responsible for the diversity and
      functional specialization of the cell types that compose an organism. The outcome
      of these processes can be studied at molecular, physiologic, and biochemical
      levels by comparing different cell types, but the complexity and dynamics of the
      regulatory processes that specify the differentiation are largely unexplored.
      RESULTS: Here we identified the pollen-specific MIKC* class of MADS-domain
      transcription factors as major regulators of transcriptome dynamics during male
      reproductive cell development in Arabidopsis thaliana. Pollen transcript
      profiling of mutants deficient in different MIKC* protein complexes revealed that
      they control a transcriptional switch that directs pollen maturation and that is
      essential for pollen competitive ability. We resolved the functional redundancy
      among the MIKC* proteins and uncovered part of the underlying network by
      identifying the non-MIKC* MADS-box genes AGL18 and AGL29 as downstream regulators
      of a subset of the MIKC* MADS-controlled genes. CONCLUSION: Our results provide a
      first, unique, and compelling insight into the complexity of a transcription
      factor network that directs cellular differentiation during pollen maturation, a
      process that is essential for male reproductive fitness in flowering plants.

PMID- 18034897
TI  - Epithelial expression of TLR4 is modulated in COPD and by steroids, salmeterol
      and cigarette smoke.
AB  - The toll-like receptors (TLRs) are a key component of host defense in the
      respiratory epithelium. Cigarette smoking is associated with increased
      susceptibility to infection, while COPD is characterised by bacterial
      colonisation and infective exacerbations. We found reduced TLR4 gene expression
      in the nasal epithelium of smokers compared with non-smoking controls, while TLR2
      expression was unchanged. Severe COPD was associated with reduced TLR4 expression
      compared to less severe disease, with good correlation between nasal and tracheal
      expression. We went on to examine the effect of potential modulators of TLR4
      expression in respiratory epithelium pertinent to airways disease. Using an
      airway epithelial cell line, we found a dose-dependent downregulation in TLR4
      mRNA and protein expression by stimulation with cigarette smoke extracts.
      Treatment with the corticosteroids fluticasone and dexamethasone resulted in a
      dose-dependent reduction in TLR4 mRNA and protein. The functional significance of
      this effect was demonstrated by impaired IL-8 and HBD2 induction in response to
      LPS. Stimulation with salmeterol (10-6 M) caused upregulation of TLR4 membrane
      protein presentation with no upregulation of mRNA, suggesting a post
      translational effect. The effect of dexamethasone and salmeterol in combination
      was additive, with downregulation of TLR4 gene expression, and no change in
      membrane receptor expression. Modulation of TLR4 in respiratory epithelium may
      have important implications for airway inflammation and infection in response to
      inhaled pathogens.

PMID- 18034898
TI  - Meaning in life in the Federal Republic of Germany: results of a representative
      survey with the Schedule for Meaning in Life Evaluation (SMiLE).
AB  - BACKGROUND: The construct "meaning-in-life" (MiL) has recently raised the
      interest of clinicians working in psycho-oncology and end-of-life care and has
      become a topic of scientific investigation. Difficulties regarding the
      measurement of MiL are related to the various theoretical and conceptual
      approaches and its inter-individual variability. Therefore the "Schedule for
      Meaning in Life Evaluation" (SMiLE), an individualized instrument for the
      assessment of MiL, was developed. The aim of this study was to evaluate MiL in a
      representative sample of the German population. METHODS: In the SMiLE, the
      respondents first indicate a minimum of three and maximum of seven areas which
      provide meaning to their life before rating their current level of importance and
      satisfaction of each area. Indices of total weighting (IoW, range 20-100), total
      satisfaction (IoS, range 0-100), and total weighted satisfaction (IoWS, range 0
      100) are calculated. RESULTS: In July 2005, 1,004 Germans were randomly selected
      and interviewed (inclusion rate, 85.3%). 3,521 areas of MiL were listed and
      assigned to 13 a-posteriori categories. The mean IoS was 81.9 +/- 15.1, the mean
      IoW was 84.6 +/- 11.9, and the mean IoWS was 82.9 +/- 14.8. In youth (16-19 y/o),
      "friends" were most important for MiL, in young adulthood (20-29 y/o)
      "partnership", in middle adulthood (30-39 y/o) "work", during retirement (60-69
      y/o) "health" and "altruism", and in advanced age (70 y/o and more)
      "spirituality/religion" and "nature experience/animals". CONCLUSION: This study
      is a first nationwide survey on individual MiL in a randomly selected,
      representative sample. The MiL areas of the age stages seem to correspond with
      Erikson's stages of psychosocial development.

PMID- 18034899
TI  - Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide.
AB  - BACKGROUND: Neurotoxic peptides derived from the protease-resistant core of the
      prion protein are used to model the pathogenesis of prion diseases. The current
      study characterised the ingestion, internalization and intracellular trafficking
      of a neurotoxic peptide containing amino acids 105-132 of the murine prion
      protein (MoPrP105-132) in neuroblastoma cells and primary cortical neurons.
      RESULTS: Fluorescence microscopy and cell fractionation techniques showed that
      MoPrP105-132 co-localised with lipid raft markers (cholera toxin and caveolin-1)
      and trafficked intracellularly within lipid rafts. This trafficking followed a
      non-classical endosomal pathway delivering peptide to the Golgi and ER, avoiding
      classical endosomal trafficking via early endosomes to lysosomes. Fluorescence
      resonance energy transfer analysis demonstrated close interactions of MoPrP105
      132 with cytoplasmic phospholipase A2 (cPLA2) and cyclo-oxygenase-1 (COX-1),
      enzymes implicated in the neurotoxicity of prions. Treatment with squalestatin
      reduced neuronal cholesterol levels and caused the redistribution of MoPrP105-132
      out of lipid rafts. In squalestatin-treated cells, MoPrP105-132 was rerouted away
      from the Golgi/ER into degradative lysosomes. Squalestatin treatment also reduced
      the association between MoPrP105-132 and cPLA2/COX-1. CONCLUSION: As the observed
      shift in peptide trafficking was accompanied by increased cell survival these
      studies suggest that the neurotoxicity of this PrP peptide is dependent on
      trafficking to specific organelles where it activates specific signal
      transduction pathways.

PMID- 18034900
TI  - Randomised controlled comparison of the Health Survey Short Form (SF-12) and the
      Graded Chronic Pain Scale (GCPS) in telephone interviews versus self-administered
      questionnaires. Are the results equivalent?
AB  - BACKGROUND: The most commonly used survey methods are self-administered
      questionnaires, telephone interviews, and a mixture of both. But until now
      evidence out of randomised controlled trials as to whether patient responses
      differ depending on the survey mode is lacking. Therefore this study assessed
      whether patient responses to surveys depend on the mode of survey administration.
      The comparison was between mailed, self-administered questionnaires and telephone
      interviews. METHODS: A four-armed, randomised controlled two-period change-over
      design. Each patient responded to the same survey twice, once in written form and
      once by telephone interview, separated by at least a fortnight. The study was
      conducted in 2003/2004 in Germany. 1087 patients taking part in the German
      Acupuncture Trials (GERAC cohort study), who agreed to participate in a survey
      after completing acupuncture treatment from an acupuncture-certified family
      physician for headache, were randomised. Of these, 823 (664 women) from the ages
      of 18 to 83 (mean 51.7) completed both parts of the study. The main outcome
      measure was the comparison of the scores on the 12-Item Short-Form Health Survey
      (SF-12) and the Graded Chronic Pain Scale (GCPS) questionnaire for the two survey
      modes. RESULTS: Computer-aided telephone interviews (CATI) resulted in
      significantly fewer missing data (0.5%) than did mailed questionnaires (2.8%; p <
      0.001). The analysis of equivalence revealed a difference between the survey
      modes only for the SF-12 mental scales. On average, reported mental status score
      was 3.5 score points (2.9 to 4.0) lower on the self-administered questionnaire
      compared to the telephone interview. The order of administration affected
      results. Patients who responded to the telephone interview first reported better
      mental health in the subsequent paper questionnaire (mean difference 2.8 score
      points) compared to those who responded to the paper questionnaire first (mean
      difference 4.1 score points). CONCLUSION: Despite the comparatively high cost of
      telephone interviews, they offer clear advantages over mailed self-administered
      questionnaires as regards completeness of data. Only items concerning mental
      status were dependent on the survey mode and sequence of administration. Items on
      physical status were not affected. Normative data for standardized telephone
      questionnaires could contribute to a better comparability with the results of the
      corresponding standardized paper questionnaires.

PMID- 18034901
TI  - Glacial vicariance in Eurasia: mitochondrial DNA evidence from Scots pine for a
      complex heritage involving genetically distinct refugia at mid-northern latitudes
      and in Asia Minor.
AB  - BACKGROUND: At the last glacial maximum, Fennoscandia was covered by an ice sheet
      while the tundra occupied most of the rest of northern Eurasia. More or less
      disjunct refugial populations of plants were dispersed in southern Europe, often
      trapped between mountain ranges and seas. Genetic and paleobotanical evidences
      indicate that these populations have contributed much to Holocene recolonization
      of more northern latitudes. Less supportive evidence has been found for the
      existence of glacial populations located closer to the ice margin. Scots pine
      (Pinus sylvestris L.) is a nordic conifer with a wide natural range covering much
      of Eurasia. Fractures in its extant genetic structure might be indicative of
      glacial vicariance and how different refugia contributed to the current
      distribution at the continental level. The population structure of Scots pine was
      investigated on much of its Eurasian natural range using maternally inherited
      mitochondrial DNA polymorphisms. RESULTS: A novel polymorphic region of the Scots
      pine mitochondrial genome has been identified, the intron 1 of nad7, with three
      variants caused by insertions-deletions. From 986 trees distributed among 54
      populations, four distinct multi-locus mitochondrial haplotypes (mitotypes) were
      detected based on the three nad7 intron 1 haplotypes and two previously reported
      size variants for nad1 intron B/C. Population differentiation was high (GST =
      0.657) and the distribution of the mitotypes was geographically highly
      structured, suggesting at least four genetically distinct ancestral lineages. A
      cosmopolitan lineage was widely distributed in much of Europe throughout eastern
      Asia. A previously reported lineage limited to the Iberian Peninsula was
      confirmed. A new geographically restricted lineage was found confined to Asia
      Minor. A new lineage was restricted to more northern latitudes in northeastern
      Europe and the Baltic region. CONCLUSION: The contribution of the various
      ancestral lineages to the current distribution of Scots pine was asymmetric and
      extant endemism reflected the presence of large geographic barriers to migration.
      The results suggest a complex biogeographical history with glacial refugia shared
      with temperate plant species in southern European Peninsulas and Asia Minor, and
      a genetically distinct glacial population located more North. These results
      confirm recent observations for cold tolerant species about the possible
      existence of refugial populations at mid-northern latitudes contributing
      significantly to the recolonization of northern Europe. Thus, Eurasian
      populations of nordic plant species might not be as genetically homogenous as
      assumed by simply considering them as offsets of glacial populations located in
      southern peninsulas. As such, they might have evolved distinctive genetic
      adaptations during glacial vicariance, worth evaluating and considering for
      conservation.

PMID- 18034902
TI  - Overcoming viral escape with vaccines that generate and display antigen diversity
      in vivo.
AB  - BACKGROUND: Viral diversity is a key problem for the design of effective and
      universal vaccines. Virtually, a vaccine candidate including most of the
      diversity for a given epitope would force the virus to create escape mutants
      above the viability threshold or with a high fitness cost. PRESENTATION OF THE
      HYPOTHESIS: Therefore, I hypothesize that priming the immune system with
      polyvalent vaccines where each single vehicle generates and displays multiple
      antigen variants in vivo, will elicit a broad and long-lasting immune response
      able to avoid viral escape. TESTING THE HYPOTHESIS: To this purpose, I propose
      the use of yeasts that carry virus-like particles designed to pack the antigen
      coding RNA inside and replicate it via RNA-dependent RNA polymerase. This would
      produce diversity in vivo limited to the target of interest and without killing
      the vaccine vehicle. IMPLICATIONS OF THE HYPOTHESIS: This approach is in contrast
      with peptide cocktails synthesized in vitro and polyvalent strategies where every
      cell or vector displays a single or definite number of mutants; but similarly to
      all them, it should be able to overcome original antigenic sin, avoid major
      histocompatibility complex restriction, and elicit broad cross-reactive immune
      responses. Here I discuss additional advantages such as minimal global antagonism
      or those derived from using a yeast vehicle, and potential drawbacks like
      autoimmunity. Diversity generated by this method could be monitored both
      genotypically and phenotypically, and therefore selected or discarded before use
      if needed.

PMID- 18034903
TI  - Discomfort and agitation in older adults with dementia.
AB  - BACKGROUND: A majority of patients with dementia present behavioral and
      psychological symptoms, such as agitation, which may increase their suffering, be
      difficult to manage by caregivers, and precipitate institutionalization. Although
      internal factors, such as discomfort, may be associated with agitation in
      patients with dementia, little research has examined this question. The goal of
      this study is to document the relationship between discomfort and agitation
      (including agitation subtypes) in older adults suffering from dementia. METHODS:
      This correlational study used a cross-sectional design. Registered nurses (RNs)
      provided data on forty-nine residents from three long-term facilities.
      Discomfort, agitation, level of disability in performing activities of daily
      living (ADL), and severity of dementia were measured by RNs who were well
      acquainted with the residents, using the Discomfort Scale for patients with
      Dementia of the Alzheimer Type, the Cohen-Mansfield Agitation Inventory, the ADL
      subscale of the Functional Autonomy Measurement System, and the Functional
      Assessment Staging, respectively. RNs were given two weeks to complete and return
      all scales (i.e., the Cohen-Mansfield Agitation Inventory was completed at the
      end of the two weeks and all other scales were answered during this period).
      Other descriptive variables were obtained from the residents' medical file or
      care plan. RESULTS: Hierarchical multiple regression analyses controlling for
      residents' characteristics (sex, severity of dementia, and disability) show that
      discomfort explains a significant share of the variance in overall agitation
      (28%, p < 0.001), non aggressive physical behavior (18%, p < 0.01) and verbally
      agitated behavior (30%, p < 0.001). No significant relationship is observed
      between discomfort and aggressive behavior but the power to detect this specific
      relationship was low. CONCLUSION: Our findings provide further evidence of the
      association between discomfort and agitation in persons with dementia and reveal
      that this association is particularly strong for verbally agitated behavior and
      non aggressive physical behavior.

PMID- 18034904
TI  - Psychosocial predictors of sexual initiation and high-risk sexual behaviors in
      early adolescence.
AB  - BACKGROUND: This longitudinal study examined psychosocial factors associated with
      risky sexual behavior in early adolescence. METHODS: Data were collected through
      a self-report survey, the Social and Health Assessment (SAHA), which was
      administered in three waves between 2001 and 2003 to a cohort of incoming sixth
      grade students in the public school system (149 classes at 17 middle and high
      schools, N = 1,175) of a small northeastern city in the United States.We first
      examined whether internalizing and externalizing problems in sixth grade, and the
      rate of change in these factors during middle school, were predictive of sexual
      initiation two years later, when most of the sample was in eighth grade. We then
      assessed whether internalizing and externalizing problems in sixth grade, and the
      rate of change in these factors during middle school, were predictive of engaging
      in high risk sexual behavior over the subsequent two years. RESULTS:
      Externalizing factors are more predictive of sexual risk in early adolescence
      than are internalizing factors. Specifically, substance use and violent
      delinquency over the course of middle school were associated with higher, while
      anxiety with lower, sexual initiation rates during middle school. Additionally,
      increased substance use over the course of middle school was associated with
      greater likelihood of engaging in high risk sexual behavior. CONCLUSION: By
      identifying particular psychosocial risk factors among young adolescents, the
      findings of this study have implications for designing multi-dimensional programs
      aimed at preventing health-compromising sexual behavior among young teens.

PMID- 18034905
TI  - Large-scale genomic 2D visualization reveals extensive CG-AT skew correlation in
      bird genomes.
AB  - BACKGROUND: Bird genomes have very different compositional structure compared
      with other warm-blooded animals. The variation in the base skew rules in the
      vertebrate genomes remains puzzling, but it must relate somehow to large-scale
      genome evolution. Current research is inclined to relate base skew with mutations
      and their fixation. Here we wish to explore base skew correlations in bird
      genomes, to develop methods for displaying and quantifying such correlations at
      different scales, and to discuss possible explanations for the peculiarities of
      the bird genomes in skew correlation. RESULTS: We have developed a method called
      Base Skew Double Triangle (BSDT) for exhibiting the genome-scale change of AT/CG
      skew as a two-dimensional square picture, showing base skews at many scales
      simultaneously in a single image. By this method we found that most chicken
      chromosomes have high AT/CG skew correlation (symmetry in 2D picture), except for
      some microchromosomes. No other organisms studied (18 species) show such high
      skew correlations. This visualized high correlation was validated by three kinds
      of quantitative calculations with overlapping and non-overlapping windows, all
      indicating that chicken and birds in general have a special genome structure.
      Similar features were also found in some of the mammal genomes, but clearly much
      weaker than in chickens. We presume that the skew correlation feature evolved
      near the time that birds separated from other vertebrate lineages. When we
      eliminated the repeat sequences from the genomes, the AT and CG skews correlation
      increased for some mammal genomes, but were still clearly lower than in chickens.
      CONCLUSION: Our results suggest that BSDT is an expressive visualization method
      for AT and CG skew and enabled the discovery of the very high skew correlation in
      bird genomes; this peculiarity is worth further study. Computational analysis
      indicated that this correlation might be a compositional characteristic, present
      not only in chickens, but also remained or developed in some mammals during
      evolution. Special aspects of bird metabolism related to e.g. flight may be the
      reason why birds evolved or retained the skew correlation. Our analysis also
      indicated that repetitive DNA sequence elements need to be taken into account in
      studying the evolution of the correlation between AT and CG skews.

PMID- 18034906
TI  - Suicidal ideation and associated factors among school-going adolescents in rural
      Uganda.
AB  - BACKGROUND: Mental health is a neglected area of health research and practice in
      most of sub-Saharan African countries where the largest burden of morbidity is
      from infectious diseases. This even occurs despite the fact that some mental
      health problems may arise from infectious diseases. METHODS: We conducted
      secondary analysis of the Uganda Global School-Based Health Survey-2003 to obtain
      the prevalence of, and assess factors that may be associated with suicidal
      ideation among school-going adolescents in rural Uganda. Assessment of
      association was conducted through both bi-variate and multivariate logistic
      regression analysis. RESULTS: Altogether 21.6% of the study participants, 21.3%
      males and 23.5% females had seriously considered committing suicide within the
      past 12 months. Loneliness, worry were positively associated with suicide
      ideation after adjusting for age, gender, smoking, drinking, and experience of
      having been bullied (OR = 1.59; 95% CI [1.12, 2.26] and OR = 1.19; 95% CI [1.12,
      2.25]) respectively. Males were less likely to seriously consider committing
      suicide than females (OR = 0.70; 95% CI [0.50, 0.98]). CONCLUSION: Adolescent
      suicidal ideation is a major public health issue in rural Uganda. Measures aimed
      to prevent adolescent suicides in Uganda should incorporate our understanding of
      factors that are associated with suicide in rural Uganda such the gender
      disparity and the association observed with substance use.

PMID- 18034907
TI  - Ebstein's Anomaly: anatomo-echocardiographic correlation.
AB  - OBJECTIVE: The aim of this investigation is to demonstrate that in Ebstein's
      Anomaly (EA) the right ventricle (RV) is affected in its three portions and to
      establish an anatomoechocardiographic correlation between the anatomic features
      and the equivalent echocardiographic images. METHODS: Thirty hearts with EA were
      studied. The alterations of each portions of the RV were described. Fifty adult
      patients with this anomaly were studied by echocardiography. RESULTS: Anatomy:
      All hearts had atrial situs solitus, 27 had concordant atrioventricular
      connection and 3 discordant, of these 2 had transposition of the great arteries
      (TGA) and one double outlet right ventricle (DORV). The degree of tricuspid valve
      (TV) displacement showed a spectrum from I to III. The inlet of the RV was
      markedly thin in 27. The trabecular portion had multiples muscular bands in all.
      The outlet portion was dilated in 20 and stenotic in 5. In 25 atrial septal
      defects were found. Echocardiography: All patients had atrial situs solitus, 42
      with concordant atrioventricular connection and 8 with discordant, of these last
      patients 5 had TGA and 3 DORV. The degree of TV displacement varied from I to
      III. The inlet of RV was markedly thin in 42. The trabecular portion had muscular
      bands in 45. The outlet portion was dilated in 31 and stenotic in 11. In 30
      atrial septal defects were found. CONCLUSION: The EA affects the whole RV and the
      anatomoechocardiographic correlation provides an appropriate understanding of
      echocardiographic images in terms of a precise diagnosis, therapeutic decisions
      and prognosis.

PMID- 18034908
TI  - Prevalence and correlates of truancy among adolescents in Swaziland: findings
      from the Global School-Based Health Survey.
AB  - BACKGROUND: Educational attainment is an important determinant of diverse health
      outcomes. Truancy among adolescents jeopardizes chances of achieving their
      educational goals. Truant behaviors are also associated with various psychosocial
      problems. There is however limited data on the prevalence and factors associated
      with truancy among adolescents in Africa. METHODS: We used data from the
      Swaziland Global School-Based Health Survey (GSHS) conducted in 2003 to estimate
      the prevalence of self-reported truancy within the last 30 days among
      adolescents. We also assessed the association between self-reported truancy and a
      selected list of independent variables using logistic regression analysis.
      RESULTS: A total of 7341 students participated in the study. In analysis of
      available data, 2526 (36.2%) and 4470 (63.8%) were males and females
      respectively. The overall prevalence of truancy within the last 30 days preceding
      the study was 21.6%. Prevalence of truancy was 27.4% (605) and 17.9% (723) in
      males and females respectively. In multivariate logistic regression analysis,
      being a male, having been bullied, lower school grades, and alcohol use were
      positively associated with truancy. Adolescents who perceived themselves as
      having parental support were less likely to have reported being truant.
      CONCLUSION: Truancy among adolescents in Swaziland should be regarded as an
      important social problem as it is relatively prevalent. The design and
      implementation of intervention programs aimed to reduce truant behaviours should
      incorporate our knowledge of the factors identified as associated with bullying.

PMID- 18034909
TI  - A set of genes previously implicated in the hypoxia response might be an
      important modulator in the rat ear tissue response to mechanical stretch.
AB  - BACKGROUND: Wounds are increasingly important in our aging societies. Pathologies
      such as diabetes predispose patients to chronic wounds that can cause pain,
      infection, and amputation. The vacuum assisted closure device shows remarkable
      outcomes in wound healing. Its mechanism of action is unclear despite several
      hypotheses advanced. We previously hypothesized that micromechanical forces can
      heal wounds. To understand better the biological response of soft tissue to
      forces, rat ears in vivo were stretched and their gene expression patterns over
      time obtained. The absolute enrichment (AE) algorithm that obtains a combined up
      and down regulated picture of the expression analysis was implemented. RESULTS:
      With the use of AE, the hypoxia gene set was the most important at a highly
      significant level. A co-expression network analysis showed that important co
      regulated members of the hypoxia pathway include a glucose transporter (slc2a8),
      heme oxygenase, and nitric oxide synthase2 among others. CONCLUSION: It appears
      that the hypoxia pathway may be an important modulator of response of soft tissue
      to forces. This finding gives us insights not only into the underlying biology,
      but also into clinical interventions that could be designed to mimic within
      wounded tissue the effects of forces without all the negative effects that forces
      themselves create.

PMID- 18034910
TI  - Analysis of cDNA libraries from developing seeds of guar (Cyamopsis tetragonoloba
      (L.) Taub).
AB  - BACKGROUND: Guar, Cyamopsis tetragonoloba (L.) Taub, is a member of the
      Leguminosae (Fabaceae) family and is economically the most important of the four
      species in the genus. The endosperm of guar seed is a rich source of mucilage or
      gum, which forms a viscous gel in cold water, and is used as an emulsifier,
      thickener and stabilizer in a wide range of foods and industrial applications.
      Guar gum is a galactomannan, consisting of a linear (1-->4)-beta-linked D-mannan
      backbone with single-unit, (1-->6)-linked, alpha-D-galactopyranosyl side chains.
      To better understand regulation of guar seed development and galactomannan
      metabolism we created cDNA libraries and a resulting EST dataset from different
      developmental stages of guar seeds. RESULTS: A database of 16,476 guar seed ESTs
      was constructed, with 8,163 and 8,313 ESTs derived from cDNA libraries I and II,
      respectively. Library I was constructed from seeds at an early developmental
      stage (15-25 days after flowering, DAF), and library II from seeds at 30-40 DAF.
      Quite different sets of genes were represented in these two libraries.
      Approximately 27% of the clones were not similar to known sequences, suggesting
      that these ESTs represent novel genes or may represent non-coding RNA. The high
      flux of energy into carbohydrate and storage protein synthesis in guar seeds was
      reflected by a high representation of genes annotated as involved in signal
      transduction, carbohydrate metabolism, chaperone and proteolytic processes, and
      translation and ribosome structure. Guar unigenes involved in galactomannan
      metabolism were identified. Among the seed storage proteins, the most abundant
      contig represented a conglutin accounting for 3.7% of the total ESTs from both
      libraries. CONCLUSION: The present EST collection and its annotation provide a
      resource for understanding guar seed biology and galactomannan metabolism.

PMID- 18034911
TI  - Pattern of beverage consumption and long-term association with body-weight status
      in German adolescents--results from the DONALD study.
AB  - In the present study the relationship between the consumption of different
      beverage groups and body-weight status in 5 years of study participation in
      German adolescents was investigated. We used anthropometric and dietary data from
      3 d weighed records of 244 subjects between 9 and 18 years of age participating
      in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD)
      study. Only subjects with at least four out of six possible weighed dietary
      records were considered. A repeated-measures regression model (PROC MIXED) was
      used to analyse the effect of beverage consumption on body-weight status. BMI
      standard deviation scores (BMI-SDS) and body fat percentage (%BF) were chosen as
      the dependent variables. In boys, energetic beverage consumption was not
      associated with BMI-SDS or %BF, neither cross-sectionally nor prospectively. In
      girls, baseline consumption of energetic beverages did not predict baseline BMI
      SDS, baseline %BF, or change in either variable over the study period. However,
      an increase in energetic beverage consumption over the study period was
      associated with an increase in BMI-SDS (+0.070 SDS/MJ increase in energetic
      beverage consumption; P = 0.01). Separate consideration of regular soft drinks
      and fruit juices revealed that, in girls, BMI-SDS increased with increased fruit
      juice consumption (+0.096 SDS/MJ increase in fruit juice consumption; P = 0.01),
      and to a lesser extent with regular soft drink consumption (+0.055 SDS/MJ
      increase in regular soft drink consumption; P = 0.08). In conclusion, these
      results suggest that an increase in energetic beverage consumption may result in
      weight gain, at least in adolescent girls.

PMID- 18034912
TI  - Sugar-sweetened beverages, weight gain and nutritional epidemiological study
      design.

PMID- 18034914
TI  - Spontaneous cervical surgical emphysema following childbirth.
AB  - OBJECTIVE: We report a case of post-partum surgical cervical emphysema, which is
      a rare but well recognised complication of labour. By reporting the first case in
      the ENT literature, we aim to raise awareness of this complication, particularly
      amongst trainees, to ensure that patients are managed most appropriately. CASE
      REPORT: A 36-year-old, primigravida woman developed neck swelling and odynophagia
      post-partum. Surgical cervical emphysema was palpated, with further examination
      excluding pneumomediastinum and pneumothorax. The patient was managed
      conservatively, with complete resolution of symptoms within a week. CONCLUSIONS:
      Surgical cervical emphysema, pneumothorax and pneumomediastinum are all well
      recognised post-partum complications. The vast majority of cases do not present
      with respiratory or cardiac compromise and can be appropriately managed
      conservatively, with expectation of resolution in a fortnight. There is no
      evidence that such patients are at increased risk during subsequent pregnancies.

PMID- 18034916
TI  - Illusion of control by proxy: placing one's fate in the hands of another.
AB  - In the present set of studies, we investigated how perceptions of other people's
      luck are used in an attempt to maximize one's own outcomes. Specifically, it was
      hypothesized that people will defer to a lucky other in games of chance to
      maximize winning potential, i.e. the illusion of control by proxy. In Experiment
      1, participants were told that they would receive a scratch-and-win lottery
      ticket as a gratuity for participating. As hypothesized, participants were more
      likely to allow a confederate to either pick their lottery ticket if they
      perceived the confederate to be personally lucky than if such perceptions where
      not facilitated. In Experiments 2 and 3, participants interacted with a
      confederate over the Internet. As predicted, participants were more likely to
      allow a gambling partner (a confederate) to spin a roulette wheel (Experiment 2),
      and bet more money on the outcome of the spin (Experiment 3) if they were made to
      believe their partner was lucky. The expanded reach of the illusion of control
      phenomena is discussed.

PMID- 18034917
TI  - Exploring the boundary conditions of expressive writing: In search of the right
      recipe.

PMID- 18034918
TI  - Molecular basis of the potential of vitamin D to prevent cancer.
AB  - OBJECTIVE: To review current research findings in cell biology, epidemiology,
      preclinical, and clinical trials on the protective effects of vitamin D against
      the development of cancers of the breast, colon, prostate, lung, and ovary.
      Current recommendations for optimal vitamin D status, the movement towards
      revision of standards, and reflections on healthy exposure to sunlight are also
      reviewed. Search methodology: A literature search was conducted in April and
      updated in September 2007. The Medline and Web of Knowledge databases were
      searched for primary and review articles published between 1970 and 2007, using
      the search terms 'vitamin D', 'calcitriol', 'cancer', 'chemoprevention', 'nuclear
      receptor', 'vitamin D receptor', 'apoptosis', 'cell cycle', 'epidemiology', and
      'cell adhesion molecule'. Articles that focused on epidemiological, preclinical,
      and clinical evidence for vitamin D's effects were selected and additional
      articles were obtained from reference lists of the retrieved articles. FINDINGS:
      An increasing body of research supports the hypothesis that the active form of
      vitamin D has significant, protective effects against the development of cancer.
      Epidemiological studies show an inverse association between sun exposure, serum
      levels of 25(OH)D, and intakes of vitamin D and risk of developing and/or
      surviving cancer. The protective effects of vitamin D result from its role as a
      nuclear transcription factor that regulates cell growth, differentiation,
      apoptosis and a wide range of cellular mechanisms central to the development of
      cancer. A significant number of individuals have serum vitamin D levels lower
      than what appears to protect against cancer, and the research community is
      currently revising the guidelines for optimal health. This will lead to improved
      public health policies and to reduced risk of cancer. CONCLUSIONS: Research
      strongly supports the view that efforts to improve vitamin D status would have
      significant protective effects against the development of cancer. The clinical
      research community is currently revising recommendations for optimal serum levels
      and for sensible levels of sun exposure, to levels greater than previously
      thought. Currently, most experts in the field believe that intakes of between
      1000 and 4000 IU will lead to a more healthy level of serum 25(OH)D, at
      approximately 75 nmol/L that will offer significant protection effects against
      cancers of the breast, colon, prostate, ovary, lungs, and pancreas. The first
      randomized trial has shown significant protection against breast cancer, and
      other clinical trials will follow and ultimately lead to improved public health
      policies and significantly fewer cancers.

PMID- 18034919
TI  - Treatment and costs associated with anemic chronic kidney disease patients.
AB  - OBJECTIVE: The purpose of this paper is to provide an overview of the current
      therapeutic options afforded to anemic chronic kidney disease (CKD) patients and
      the costs of these interventions. METHODOLOGY: Literature search of articles
      within Ovid MEDLINE between 1996 and 2007 that pertained to the treatment of
      anemia in chronic kidney disease patients. RESULTS: Early detection and treatment
      of anemia associated with CKD has proven to provide positive cognitive and
      physical effects. Treatment options that increase iron storage and availability
      within the body and production of erythropoietin can assist in anemic CKD
      patients in achieving recommended levels of hemoglobin. Acknowledgement of the
      potential side effects associated with the medications selected to treat anemia
      can help in avoiding additional injury to the patient and thus reduce healthcare
      expenditure. A limitation of this review is that the search was performed within
      a single database. CONCLUSIONS: Health care providers can play an active role in
      detecting anemia early and optimizing available treatment options. Future
      research on the effects of erythropoiesis-stimulating agents (ESA) on patients
      before they need dialysis, and a cost analysis between epoetin and darbepoetin
      alpha, would be beneficial.

PMID- 18034920
TI  - Use of 2-octyl cyanoacrylate for skin closure of sternal incisions in cardiac
      surgery: observations of microbial barrier effects.
AB  - INTRODUCTION: The systematic use of 2-octyl cyanoacrylate (2-OCA) became routine
      in our cardiac unit in 2000. This topical skin adhesive has been used in
      conjunction with conventional suturing for skin closure and prevention of
      postoperative wound infections by means of its performance as a microbial barrier
      to exogenous bacteria. It is, therefore, important to validate its effectiveness
      in the reduction of infection rates and, consequently, in the length of
      postoperative hospital stays. OBJECTIVE: To evaluate the impact of the use of 2
      OCA as an add-on measure in the closure of sternotomy incision wounds by
      comparing postoperative infection rates and length of hospital stays before and
      after this procedural change. METHODS: We reviewed the records of 680 patients
      whose cardiovascular surgery performed between 2000 and 2004 included the use of
      2-OCA and an equal number of patients who did not receive the topical skin
      adhesive (surgeries performed between 1995 and 1999), used as a control group.
      RESULTS: From 1995 to 1999 (without the topical skin adhesive) the infection rate
      was 4.9%. This rate was reduced to 2.1% after the systematic use of the topical
      skin adhesive (p < 0.001). Superficial and deep infection rates decreased from
      4.3% and 0.6% to 2.1% and 0%, respectively. Postoperative hospital stays were
      also significantly reduced, decreasing from a median of 13 days to 9 days (p <
      0.001). CONCLUSION: From the patient records reviewed in this study, it was found
      that the routine use of 2-octyl cyanoacrylate as an add-on measure to
      conventional sutures was associated with a significant reduction in infection
      rates for cardiovascular surgery patients.

PMID- 18034921
TI  - Self construction in schizophrenia: a discourse analysis.
AB  - OBJECTIVES: Lysaker and Lysaker (Theory and Psychology, 12(2), 207-220, 2002)
      employ a dialogical theory of self in their writings on self disruption in
      schizophrenia. It is argued here that this theory could be enriched by
      incorporating a discursive and social constructionist model of self. Harr's model
      enables researchers to use subject positions to identify self construction in
      people with a diagnosis of schizophrenia that the dialogical model, using
      analysis of narrative, does not as easily recognize. METHODS: The paper presents
      a discourse analysis of self construction in eight participants with a diagnosis
      of schizophrenia. Transcripts from semi-structured interviews are analysed,
      wherein focus falls on how participants construct self in talk through the use of
      subject positioning. RESULTS: The findings indicate that Harr's theory of self
      and the implied method of discourse analysis enables more subtle and nuanced
      constructions of self to be identified than those highlighted by Lysaker and
      Lysaker (Theory and Psychology, 12(2), 207-220, 2002). The analysis of subject
      positions revealed that participants constructed self in the form of Harr's (The
      singular self: An introduction to the psychology of personhood, 1998, London:
      Sage) self1, self2, and self3. The findings suggest that there may be
      constructions of self used by people diagnosed with schizophrenia that are not
      recognized by the current research methods focusing on narrative. The paper
      argues for the recognition of these constructions and by implication a model of
      self that takes into account different levels of visibility of self construction
      in talk.

PMID- 18034945
TI  - HIV/AIDS 2007: an end-of-year commentary.

PMID- 18034946
TI  - The consequences of smoking and tobacco on lung disease in developing countries:
      plenary lecture given during the 37th Union World Conference on Lung Health,
      Palais des Congres, Paris, France, 31 October-4 November 2006.

PMID- 18034947
TI  - Ethics Advisory Group of the International Union Against Tuberculosis and Lung
      Disease: policy and operational guidelines.

PMID- 18034948
TI  - Paradoxical response during anti-tuberculosis treatment in HIV-negative patients
      with pulmonary tuberculosis.
AB  - BACKGROUND: Transient worsening of tuberculosis (TB) symptoms and lesions
      following anti-tuberculosis treatment (paradoxical response [PR]), has been
      described in human immunodeficiency virus (HIV) infected patients who undergo
      anti-tuberculosis treatment. The frequency and clinical presentations for PR in
      HIV-negative patients with pulmonary TB are unknown. OBJECTIVE: To determine the
      incidence of PR and its associated manifestations in a retrospective study of HIV
      negative patients with pulmonary TB. RESULTS: Of 659 TB patients, 16 developed
      PR, with an incidence of 2.4%. The medium onset time of PR was 26 days. Recurrent
      fever was the most common clinical manifestation. Compared with 643 patients
      without PR, patients developing PR had significantly decreased haemoglobin,
      albumin, body mass index and baseline lymphocyte counts. There was a noticeable
      increase in the lymphocyte count during paradoxical deterioration in PR subjects
      than in the control group. Independent factors for developing PR included
      anaemia, hypoalbuminaemia, lymphopaenia and lymphocyte count increase during PR
      development. CONCLUSIONS: The clinical manifestations of PR in patients with
      pulmonary TB were different from those in patients with extra-pulmonary TB.
      Baseline anaemia, hypoalbuminaemia, lymphopaenia and a greater change in
      lymphocyte count were independent risk factors for developing PR.

PMID- 18034949
TI  - Feasibility of routine HIV testing among TB patients through a voluntary
      counselling and testing centre.
AB  - BACKGROUND: Despite the synergy between the human immunodeficiency virus (HIV)
      and tuberculosis (TB) epidemics, the public health responses have largely been
      separate. Detection of HIV among TB patients is crucial to the holistic
      management of HIV-TB co-infected patients. OBJECTIVE: To assess the feasibility
      of screening all TB patients for HIV through referral to a voluntary counselling
      and testing centre. DESIGN: This cross-sectional study of 4802 newly diagnosed TB
      patients between July 2005 and June 2006 was performed in Tamilnadu, India, at
      six sites. RESULTS: Of 4802 patients invited, 69% were willing to participate in
      the test. The most significant variables that influenced willingness were sex,
      age and place of residence (P < 0.01). The other significant variables that
      influenced willingness to participate were higher education, being employed and
      being married (P < 0.05). The main reasons for refusal of HIV screening among the
      patients were 'no risk behaviour' (30%), followed by 'too old' (23%) and for
      reasons of privacy (12%). CONCLUSIONS: The present study suggests that it is
      feasible to routinely test TB patients for HIV. However it is crucial for health
      providers to focus on an effective referral process keeping patient concerns in
      mind. Motivation strategies need to be sex-, age-, education- and residence
      specific.

PMID- 18034951
TI  - TB presenting as community-acquired pneumonia in a setting of high TB incidence
      and high HIV prevalence.
AB  - SETTING: Sub-Saharan Africa has the highest prevalence of human immunodeficiency
      virus (HIV)/acquired immune-deficiency syndrome (AIDS) and a high incidence of
      tuberculosis (TB). OBJECTIVES: To determine the aetiology of and mortality due to
      community-acquired pneumonia (CAP) in HIV and non-HIV-infected adults. METHODS:
      Consecutive patients with CAP admitted to a teaching hospital in KwaZulu-Natal
      over a 17-month period were studied prospectively. Systematic investigation of
      samples of sputum and blood cultures was performed. A subset of patients had
      urine antigen tests and serum serology. RESULTS: A total of 430 patients with a
      mean age of 33 years (range 18-82) were enrolled. Of the 382 patients tested, 311
      (81.4%) were HIV-infected. Pathogens were isolated in 222 patients (52%). The
      most common organisms were Mycobacterium tuberculosis (39.6%) and Streptococcus
      pneumoniae (34.5%). M. tuberculosis was the most common agent in both HIV and non
      HIV-infected subjects (40% and 35%, respectively). In-hospital mortality was 17%
      overall, 15.9% in the HIV-infected, 25% in the non-HIV-infected and 38% in
      patients with polymicrobial infections. CONCLUSIONS: M. tuberculosis was the
      leading cause of CAP and reflects the worsening TB epidemic in the region.
      Aggressive intervention is required to address both the HIV and TB epidemics in
      sub-Saharan Africa.

PMID- 18034950
TI  - Chest physiotherapy for collecting sputum samples from HIV-positive patients
      suspected of having tuberculosis.
AB  - SETTING: A public referral hospital in Sao Paulo, Brazil. OBJECTIVE: To evaluate
      chest physiotherapy as a means of obtaining sputum samples from human
      immunodeficiency virus (HIV) positive in-patients suspected of having pulmonary
      tuberculosis (TB). DESIGN: A prospective study. MATERIAL AND METHODS: Five
      consecutive samples were collected from 132 patients using the 'spontaneous'
      technique (ST) on day 1, slow expiration with the glottis open in a lateral
      posture ('expiration lente totale glotte ouverte en infralateral', ELTGOL) on day
      2, ST on day 3, sputum induction with hypertonic saline (SIHS) on day 4 and ST on
      day 5. Samples were processed for acid-fast bacilli (AFB) smear and seeded onto
      Lowenstein-Jensen medium. RESULTS: Mycobacteria were recovered from 34 patients
      (25.8%). Nine (26.5%) of the strains were identified as mycobacteria other than
      Mycobacterium tuberculosis. AFB smear sensitivity was higher in ELTGOL samples
      than in ST or SIHS samples (52.9% vs. 32.4% and 29.4%), although the difference
      among the three was not significant (P = 0.098). In culture, the three ST samples
      proved significantly more sensitive (P = 0.05). CONCLUSIONS: Physiotherapy shows
      promise as a technique for obtaining sputum from HIV-positive patients, and AFB
      testing of a single sample presents high sensitivity. However, this does not
      preclude the routine collection of three samples, as TB cannot be ruled out
      before the culture results are known.

PMID- 18034952
TI  - Adverse reactions among patients being treated for MDR-TB in Tomsk, Russia.
AB  - BACKGROUND AND SIGNIFICANCE: Treatment of multidrug-resistant tuberculosis (MDR
      TB) is challenging because of the toxicity of second-line medications. Little is
      known about whether adverse events impact treatment outcome. METHODS: We
      conducted a retrospective case series of 244 MDR-TB patients enrolled in Tomsk
      between 10 September 2000 and 10 September 2002. Adverse reactions were
      determined by laboratory data and/or clinical criteria. A multiple logistic
      regression model was performed to determine whether the occurrence of adverse
      reactions was associated with poor treatment outcome. RESULTS: In this cohort,
      76.0% were cured, 6.6% failed, 4.9% died and 11.5% defaulted. Adverse events were
      observed in 73.3% of patients, occurring in 74.8% of patients who were adherent
      (taking at least 80% of prescribed doses) and 59.1% of non-adherent individuals
      (P = 0.11). The impact of adverse events on outcome was modified by non
      adherence; among adherent patients, the occurrence of any adverse reaction was
      associated with treatment cure (adjusted odds ratio 3.24, 95% confidence interval
      1.56-6.70). CONCLUSION: Adverse reactions occurred frequently in MDR-TB patients
      in Tomsk, Russia, but did not negatively impact treatment outcome. The occurrence
      of adverse reactions among adherent patients was associated with treatment cure.

PMID- 18034953
TI  - The national tuberculosis drug resistance survey in Cambodia, 2000-2001.
AB  - SETTING: Cambodia has a high incidence of tuberculosis (TB). Hospital-based DOTS
      was predominant throughout the country from 1994 to 2002. OBJECTIVES: To
      determine the prevalence of resistance to four major anti-tuberculosis drugs,
      isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and streptomycin (SM), among
      new cases as a baseline before a new National Tuberculosis Programme strategy
      with decentralised ambulatory DOTS was widely implemented. DESIGN: A cluster
      sampling of TB diagnostic centres with probability proportional to the number of
      new cases in a diagnostic centre in 1999 was used. Intake of cases took place
      from October 2000 to April 2001. RESULTS: From 734 isolates collected, drug
      susceptibility test results were obtained for 638 new cases. The prevalence of
      resistance to any of four drugs was 10.1% (95%CI 7.7-13). Resistance to INH was
      6.1% (95%CI 4.3-8.4) and resistance to RMP 0.6% (95%CI 0.2-1.6). No multidrug
      resistant (MDR) case was found among the new cases (95%CI 0.0-0.6). Three of 96
      previously treated cases had MDR (3.1%, 95%CI 1.0-9.0). CONCLUSION: The first
      survey indicates that the current prevalence of MDR is low. It is necessary to
      track resistance trends when restructuring a DOTS-based programme.

PMID- 18034954
TI  - Nationwide survey on the prevalence of anti-tuberculosis drug resistance in the
      Republic of Yemen, 2004.
AB  - OBJECTIVES: To determine the prevalence of resistance to the four major anti
      tuberculosis drugs, isoniazid, rifampicin, streptomycin and ethambutol, in Yemen.
      METHODS: Cluster sampling with probability proportionate to size was applied.
      Susceptibility to four major anti-tuberculosis drugs was examined. The proportion
      method using Lowenstein-Jensen medium or Ogawa medium was carried out. RESULTS: A
      total of 790 primary culture isolates from tuberculosis (TB) cases enrolled at
      the National Tuberculosis Institute, Yemen, were examined. In the confirmation
      culture at the supranational reference laboratory, 227 of them failed to grow on
      the secondary culture or were proved to be mycobacteria other than Mycobacterium
      tuberculosis and were excluded from further analysis. Among 563 cultures, 510
      were obtained from new cases and 53 from previously treated cases. The prevalence
      of resistance to any four drugs was 9.8% (95%CI 7.0-12.5) among new cases and
      17.4% (95%CI 12.0-33.5) among previously treated cases. The prevalence of
      multidrug-resistant TB was 3.0% (95%CI 1.5-4.5) among new cases and 9.4% (95%CI
      0.2-18.7) among previously treated cases. CONCLUSION: The first nationwide
      prevalence survey on resistance to the four major anti-tuberculosis drugs in
      Yemen showed a relatively low prevalence of drug-resistant cases, but a high
      prevalence of multidrug resistance among new cases.

PMID- 18034955
TI  - Anti-tuberculosis drug susceptibility testing of Mycobacterium bovis BCG Tokyo
      strain.
AB  - SETTING: The Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccine is the
      only vaccine against tuberculosis (TB), owing to its valuable protective effects
      and low virulence. However, it can occasionally cause systemic infection in
      immunocompromised hosts. Isoniazid (INH), rifampicin (RMP), streptomycin (SM) and
      ethambutol (EMB) are known to be effective anti-tuberculosis drugs and are used
      for the treatment of BCG infections. Unfortunately, there are few studies of the
      susceptibility of BCG vaccine strains to these drugs. OBJECTIVE: To measure the
      minimum inhibitory concentrations (MICs) of BCG Tokyo vaccine products for anti
      tuberculosis drugs and assess vaccine safety in terms of drug susceptibility.
      DESIGN: We measured the MIC for one seed and five product lots of BCG Tokyo
      strain for INH, RMP, SM and EMB using Middlebrook 7H11 agar plates. RESULTS: The
      MIC results for INH were 0.06 and 0.125 mg/ml for the product and seed lots,
      respectively. The MIC results for RMP, SM and EMB were 0.25-0.5, 0.25 and 2-4
      microg/ml, respectively. CONCLUSION: Our results indicate that the BCG Tokyo
      strain was susceptible to the major anti-tuberculosis drugs and treatable even in
      cases of severe adverse events, including systemic infection.

PMID- 18034956
TI  - Conversion rate at two-month follow-up of smear-positive tuberculosis patients in
      Burkina Faso.
AB  - SETTING: Burkina Faso, West Africa. OBJECTIVE: 1) To determine the trend of
      sputum smear conversion rates at the 2-month follow-up of new smear-positive
      tuberculosis (TB) patients; and 2) to compare conversion rates in cured TB
      patients and treatment failures. DESIGN: Retrospective cohort study based on TB
      registers from all 80 diagnostic and treatment centres from 1995 to 2003. The
      conversion rate was defined as the number of negative results divided by the
      number of smear-positive patients for whom the 2-month follow-up examination was
      completed. RESULTS: The 2-month follow-up completion rate was 92.1%; it increased
      from 86.3% in 1996 to 94.3% in 2003. The conversion rate was 82.9%, increasing
      from 76.3% in 1995 to 87.9% in 1997 and falling to 80.3% in 2003. The cure rate
      was higher among patients who were smear-negative at the 2-month follow-up
      (77.3%) CONCLUSION: The conversion rate was satisfying, but had declined since
      1997, which may be a matter of concern. This could be due to patient
      characteristics such as associated conditions (human immunodeficiency virus,
      malnutrition) or to drug management (ineffective administration of drugs even
      under directly observed treatment, insufficient dosages, resistance). Thorough
      research is needed to elucidate this negative trend.

PMID- 18034957
TI  - Under- and over-consumption intermittent TB treatment among rural TB patients in
      south-west China.
AB  - OBJECTIVE: To assess adherence to intermittent directly observed treatment (DOT)
      during the 2-month intensive phase of tuberculosis (TB) treatment in south-west
      rural China. DESIGN: A cross-sectional study was conducted in Simao Prefecture,
      Yunnan Province, China. One hundred and thirty new TB patients registered under
      DOTS and treated during the 2-month intensive phase and their observers were
      separately interviewed at their homes using structured questionnaires. Numbers of
      packs of TB drugs were checked on the spot. RESULTS: Of 130 visits, the same
      percentage (3.1%) of patients and their observers reported missing > or =2
      consecutive weeks of treatment (prevalence-adjusted kappa = 0.94). The
      percentages who missed > or =20% of the packs, as reported by patients and
      observers, were 3.8 and 2.3, respectively (prevalence-adjusted kappa = 0.969).
      According to the pill count, nine patients (7%) had missed > or =20% of the
      packs, 10 had over-consumed TB drugs and two had lost respectively five and six
      packs. Eight of the 10 who had over-consumed had done so due to confusion in the
      days of the month, and two because they wanted a quicker recovery. CONCLUSIONS:
      Intermittent regimens in China need to be more carefully monitored to avoid over
      consumption of anti-tuberculosis drugs in addition to non-adherence due to under
      consumption.

PMID- 18034958
TI  - Computed tomography findings in urban transportation workers with low cumulative
      asbestos exposure.
AB  - OBJECTIVE: To assess the frequency of computed tomography (CT) scan pleural and
      interstitial changes in a population of urban transportation workers with low
      cumulative exposure to asbestos, and to measure inter-reader agreement. DESIGN: A
      total of 269 male volunteers (mean age 54.0 +/- 2.3 years, mean estimated
      cumulative exposure index 1.7 +/- 2.3 fibres/ml-years), underwent a CT scan which
      was read independently by three experienced readers, with further consensus
      reading in case of pleural or parenchymal abnormalities. Inter-reader agreement
      was assessed by means of Kappa statistic. RESULTS: On consensus reading, four
      subjects had interstitial opacities, three had diffuse pleural thickening and 26
      (9.7%) had pleural plaques that were unilateral in 65% of cases and < or =2 mm
      thick in 54% of cases. No correlation was observed between pleural plaques and
      latency, duration of exposure or cumulative exposure. The inter-reader agreement
      for the detection of pleural abnormalities was fair. CONCLUSION: In this
      relatively young population with low cumulative exposure to asbestos, the
      prevalence of pleural abnormalities was low. These abnormalities were very
      limited in thickness and extent, leading to marked inter-reader variability and
      making it difficult to assess their relationship to asbestos exposure.

PMID- 18034959
TI  - Smoking makes asthma expensive: a register-based study in Finland.
AB  - SETTING: Chronic bronchitis and chronic obstructive pulmonary disease
      (COPD)/emphysema occur frequently among middle-aged and elderly asthma patients
      who smoke. OBJECTIVE: To test how much this comorbidity increases the use and
      costs of health services in comparison with asthma alone. DESIGN: A sample of
      6000 adults with a clinical diagnosis of asthma was extracted from a nationwide
      health insurance register for a postal inquiry. Comorbidity and the use of health
      services were measured using a questionnaire. Data on medication expenses were
      obtained from the national prescription register. RESULTS: Altogether 4956
      individuals replied, of whom 3160 asthma patients aged > or =40 years (response
      rate 85%) were chosen for this investigation. Asthma patients with COPD/emphysema
      (12% of the series) accounted for 21% of all doctor consultations, 39% of the
      total number of hospital in-patient days and 27% of the total expenses, of which
      one third were medication costs. The mean annual gross expenditure on treatment
      services and anti-asthma medications was euro754 per patient for those with
      asthma alone and euro2107 for those with concurrent COPD/emphysema. Current
      smoking further increased costs among COPD patients. CONCLUSION: To prevent
      pulmonary comorbidity and the related high costs, cessation of smoking should be
      an integral part of the treatment provided for asthma patients.

PMID- 18034960
TI  - Cigarette smoking among adolescent females in Pakistan.
AB  - SETTING: Tobacco use among adolescent females is gaining importance as they take
      up smoking in increasing numbers. Recent studies show that sex differences in
      tobacco use are disappearing and that tobacco companies are agressively targeting
      females in developing countries. OBJECTIVE: To determine the factors influencing
      the use of cigarettes among female high-school students in Karachi, Pakistan, and
      hence to identify areas for future intervention. METHOD: A two-stage cluster
      sample of 644 females was drawn from government and private schools in a locality
      in Karachi. A self-administered questionnaire was used for data collection.
      RESULTS: The mean age was 15.29 years. The prevalence of ever-smokers was found
      to be 16.3%. Univariate analysis indicated that private school attendance,
      underage sale of tobacco at shops, tobacco use by family members and exposure to
      cigarette advertisements predicted smoking among girls. Knowledge assessment of
      the subjects showed that most girls had good knowledge about the hazards of
      smoking. CONCLUSION: Our study has identified several risk factors for smoking
      among young girls. Appropriate interventions are needed in the form of public
      education programmes, effective anti-tobacco laws and stricter enforcement of
      existing laws to restrict the number of young female smokers.

PMID- 18034961
TI  - Lung function and symptoms among indigenous Mayan women exposed to high levels of
      indoor air pollution.
AB  - SETTING: Indoor air pollution from burning of biomass fuel in open fires is a
      known risk factor for chronic obstructive pulmonary disease (COPD) in developing
      countries. OBJECTIVE: To estimate the prevalence of respiratory symptoms and lung
      function among women in rural Guatemala and to describe the methods and practical
      issues associated with the assessment of respiratory health. DESIGN: Information
      about respiratory symptoms, lung function and individual measurement of exposure
      was collected cross-sectionally among 350 Mayan-Indian women aged 15-50 years who
      used traditional open fires. RESULTS: These women, exposed to indoor air
      pollution since birth, had a relatively high prevalence of cough (22.6%), phlegm
      (15.1%), wheeze (25.1%) and tightness in the chest (31.4%). Respiratory symptoms
      were positively associated with exposure levels. Lung function was higher than
      the most feasible reference population (average above predicted forced expiratory
      volume in 1 s [FEV(1)] +4.5% and forced vital capacity [FVC] +4.2%). Only one
      woman had a FEV(1)/FVC ratio lower than 70%. CONCLUSIONS: According to the Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, almost one
      third of these young non-smoking women were at risk (stage 0) of developing COPD.
      The methodological issues encountered during the study highlight the importance
      of standardising approaches to local adaptation of established questionnaires to
      study respiratory health in rural areas of developing countries.

PMID- 18034962
TI  - 'Monitor-supervised family member' DOT: an optimal means of delivering DOT.

PMID- 18034963
TI  - Childhood tuberculosis in Latin America and the new WHO Manual.

PMID- 18034964
TI  - Boosting of Quantiferon by TST.

PMID- 18034965
TI  - Atopic Dermatitis, Genetics, Immunology, and T regulatory cells.

PMID- 18034966
TI  - Objective measures of asthma control: sputum eosinophils, nitric oxide, and other
      inflammatory mediators.
AB  - This discussion concerns the tools we can use to measure the status of
      inflammation in asthma and therefore help us diagnose and manage this condition.
      Although measurement of pulmonary function is of course a necessity, it does not
      necessarily tell us the status of activity of the disease. For example, in a
      patient with fixed lung obstruction that can occur in asthma, the forced
      expiratory volume in 1 second (FEV(1)) may be markedly low in the absence of
      disease activity. In addition, the disease may be highly active in a patient with
      normal lung functions by virtue of the fact that they are receiving therapy with
      inhaled corticosteroids and bronchodilators. Finally, measurement of disease
      activity is useful in establishing a diagnosis of asthma in a patient who is
      asymptomatic with normal lung functions at the time of presentation. Therefore,
      tools to measure the status of inflammation would be extremely helpful. In this
      article two such tools are discussed: the measurement of eosinophilia and the
      assessment of exhaled nitric oxide.

PMID- 18034967
TI  - Compliance and noncompliance in asthma.
AB  - Compliance and noncompliance are big issues in asthma management. It has been
      well established that compliant patients experience less exacerbations than less
      compliant patients and that compliance rates often are <50%. The reasons for
      noncompliance are multiple and complex and not always clearly understood. Methods
      proposed to improve compliance include patient education, more partnership care,
      less frequent dosing, simple schedules, diaries, etc. Less dosing and simple
      schedules are most effective. It is difficult to improve compliance overall and
      despite extensive research and efforts, rates of compliance remain low.
      Noncompliance in asthma management is a fact of life and no single compliance
      improving strategy probably will be as effective as a good physician-patient
      relationship.

PMID- 18034968
TI  - New concepts in the management of adverse drug reactions.
AB  - Our understanding of drug reactions and their management has changed markedly in
      recent years with the development of several new concepts. Epidermal cell death
      seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may
      result from Fas-Fas ligand-mediated apoptosis. Intravenous immunoglobulin (IVIG)
      contains anti-Fas antibodies that can abrogate apoptosis. Most studies on IVIG in
      SJS and TEN reported improvement in arresting disease progression and reduction
      in time to healing. Furthermore, several studies have dispelled the myth of
      sulfonamide cross-reactivity. Immune-mediated reactions against antibacterial
      sulfonamides are directed against two unique side chains that non-antibacterial
      sulfonamides do not contain. Certain patients seem to have a genetic
      predisposition for "multiple drug sensitivities." Hence, they may react to
      several drugs that are not necessarily cross-reacting. Also, multiple studies
      have shown that IgE-mediated nonsteroidal anti-inflammatory drugs (NSAIDs) cross
      reactivity is uncommon. Rather, it is cyclooxygenase (COX) 1 inhibition that
      results in pseudoallergic reactions to multiple NSAIDs. Several studies have
      indicated that selective COX-2 inhibitors can be safely administered in patients
      with aspirin-exacerbated respiratory disease and NSAID-induced cutaneous
      reactions, although their use has been curtailed by their cardiovascular side
      effects. Biological agents, such as infliximab, are being increasingly used for a
      variety of diseases and have caused adverse reactions in some patients. Studies
      differ as to whether concomitant immunosuppressive use with infliximab affects
      the development of drug-specific antibodies and infusion reactions. Successful
      desensitization protocols have been developed for reactions to some of these
      agents.

PMID- 18034969
TI  - FoxP3-expressing T regulatory cells in atopic dermatitis lesions.
AB  - Recently, studies were conducted to evaluate the impact of T regulatory (T regs)
      cells in the pathophysiology of atopic dermatitis (AD). The aim of this study was
      to investigate whether natural T regs are present in AD skin lesions. We
      performed skin biopsies in 12 adult patients affected by moderate-to-severe AD
      and 4 healthy volunteers. The specimens were stained immunohistochemically with
      anti-human CD25 and forkhead/winged helix transcription factor (FoxP3). Double
      immunostaining for CD25 and FoxP3 was performed also. CD25+ cells strongly
      infiltrated the perivascular and papillar dermis of all lesional specimens, and
      FoxP3+ cells were distributed in the perivascular and interstitial AD dermis, and
      some cells also infiltrated the dermoepidermal junction and the basal and
      suprabasal epidermal layers. All healthy skin specimens showed weak CD25 and
      FoxP3 stainings. Double immunostaining showed that CD25+ FoxP3+ cells were
      distributed in the perivascular, interstitial, and periadnexal dermis, and
      healthy skin specimens featured few CD25+ FoxP3+ cells scattered throughout the
      dermis. The past and present data show that an impaired function of natural T
      regs may not play a primary role in the pathophysiology of AD lesions.

PMID- 18034970
TI  - IgE values and T-lymphocyte subsets in children with atopic eczema/dermatitis
      syndrome.
AB  - High levels of IgE and IgE-mediated reactions represent a typical finding in
      patients with atopic eczema/dermatitis syndrome (AEDS). However, 10-30% of
      patients usually do not show any increase of total blood IgE levels and any
      detectable specific IgE sensitization. We performed this study to evaluate the
      difference of T-lymphocyte subsets in AEDS patients with high or normal IgE
      values. We enrolled 21 children with AEDS who were at least two years of age (8
      boys and 13 girls, aged 2-13 years) and 20 children as control cases with the
      same age and sex. These patients were classified as IgE-associated AEDS or not
      IgE-associated AEDS syndrome according to their IgE levels. We used monoclonal
      antibodies against CD3 (T cells), CD4 (T-helper cells), CD8 (T-cytotoxic cells),
      CD 19 (B cells), CD56 and CD16 (natural killer cells), CD3/HLA-DR (activated T
      cells), CD45Ra in CD4 (naive lymphocytes), CD25 (interleukin-2 receptor), CD57 in
      CD3 (suppressor/cytotoxic), and CD5 in CD20 (Becton Dickinson, Mountain View,
      CA). The severity of atopic dermatitis (AD) was determined according to the
      Scoring Atopic Dermatitis (SCORAD) index. Moreover, we checked the levels of
      peripheral blood eosinophils and of total and specific IgE for a panel of
      inhalant and food allergens. We found that the CD8+ level was significantly lower
      and the CD4/CD8 ratio was significantly higher than in healthy cases. Moreover,
      patients with not IgE associated AEDS (aAD) showed CD4+ levels significantly
      higher than IgE aAD patients and healthy controls. We found no difference of the
      SCORAD index in the two groups but there was an inverse relationship between this
      index and CD4/CD8 ratio. We did not find any correlation between IgE levels and
      the SCORAD index between eosinophils and SCORAD index or between age and IgE
      values. A decrease of CD8+ circulating T cells and an increase of the CD4/CD8
      ratio are peculiar findings in AEDS patients with either high or normal IgE
      values.

PMID- 18034971
TI  - Importance of genetic factors in the etiology of atopic dermatitis: a twin study.
AB  - The susceptibility to develop atopic dermatitis can be attributed both to genetic
      and environmental causes. We estimated the relative impact of genetic and
      environmental factors in the etiology of atopic dermatitis in a population-based
      sample of twins. From the birth cohorts of 1953-1982 who were enrolled in The
      Danish Twin Registry, a total of 11,515 twin pairs were identified in a
      nationwide questionnaire survey. Subjects were classified as atopic dermatitis
      cases when responding affirmatively to the question, "Do you have, or have you
      ever had, eczema in the folds of your elbows or knees?" Latent factor models of
      genetic and environmental influences were fitted to the observed data using
      maximum likelihood methods. The overall lifetime prevalence of atopic dermatitis
      was 7.3%. A cotwin of an affected identical twin had a sevenfold increased risk
      of atopic dermatitis compared with a threefold increased risk among cotwins of an
      affected fraternal twin, relative to the general population. Genes accounted for
      82% and nonshared environmental factors accounted for 18% of the individual
      susceptibility to develop atopic dermatitis. The same genes contributed to the
      susceptibility to atopic dermatitis both in male and female patients (p = 0.98).
      The estimates were adjusted for age. The susceptibility to develop atopic
      dermatitis is attributable to mainly genetic differences between people. However,
      differences in environmental exposures also are of importance.

PMID- 18034972
TI  - Atopic dermatitis and asthma.
AB  - Atopic dermatitis (AD), a chronic inflammatory skin disease, frequently
      associated with respiratory allergy, is one of the most common skin disorders
      observed in children. The prevalence of AD and other allergic diseases is
      increasing in industrialized countries, representing a major burden on health
      care cost. AD has been proposed as an "entry point" for subsequent allergic
      diseases, suggesting the possibility that effective management of AD could
      prevent the development of respiratory allergy or at least reduce the severity of
      asthma and allergic rhinitis. AD and asthma share a common genetic and pathogenic
      basis, and several longitudinal studies provided evidence for the atopic march
      from AD to allergic rhinitis and asthma. However, because only a few prospective
      studies starting at children's births and having a sufficiently long follow-up
      have been developed, little is known about the natural course of AD and the
      potential succession of atopic phenotypes in childhood. Finally, recent genetic
      and epidemiological data raised the question whether AD may either develop to
      asthma or be part of a syndrome consisting of both diseases.

PMID- 18034973
TI  - Esophageal candidiasis and Candida colonization in asthma patients on inhaled
      steroids.
AB  - The aim of this study was to evaluate the risk of esophageal candidiasis in
      asthma patients who are on inhaled steroids without any other risk factors for
      esophageal candidiasis by comparing the treatment group with the control group.
      Moreover, the oropharyngeal and esophageal Candida colonizations were evaluated
      in the subgroups of both control and treatment groups. Upper gastrointestinal
      system endoscopic evaluation was performed in 40 asthma patients who were on
      inhaled steroids for at least 1 month. The control group consisted of 40 steroid
      naive patients without asthma. Oral and esophageal samples were obtained for
      performing quantitative culture. Candida growth in cultures without any clinical
      signs and symptoms was described as colonization. Candida growth accompanied by
      clinical signs and symptoms was described as infection. None of the patients in
      the control group had either esophageal or oropharyngeal candidiasis; however,
      one (2.5%) asthma patient had esophageal candidiasis and two (5%) asthma patients
      had oropharyngeal candidiasis. Esophageal and oropharyngeal Candida colonization
      was determined in 5 (22.7%) and 11 (50%) of the asthma patients and 7 (31%) and 9
      (41%) of the control group, respectively. Although the mean numbers of Candida
      colonies were higher in the asthma group in both localizations, there were no
      statistically significant differences between the two groups regarding esophageal
      or oropharyngeal Candida colonization. The risk of esophageal candidiasis due to
      inhaled steroids is low and inhaled steroids may be used safely in terms of
      esophageal candidiasis. Future prospective studies are needed to draw more
      definitive conclusions.

PMID- 18034974
TI  - Gender and age risks for hoarseness and dysphonia with use of a dry powder
      fluticasone propionate inhaler in asthma.
AB  - Dry powder inhalers (DPIs) of fluticasone propionate (FP) are the most commonly
      prescribed inhaled glucocorticosteroid (ICS) devices in Japan because of their
      ease of use. FP has the strongest anti-inflammatory effects in vitro among ICS,
      and it has few systemic adverse effects because of its <1% oral bioavailability.
      However, local adverse effects, especially hoarseness or dysphonia
      (hoarseness/dysphonia), appear to be frequent. We investigated
      hoarseness/dysphonia in 313 patients with bronchial asthma who were using or had
      used the FP-DPI. Overall, 20.4% of FP-DPI users complained of
      hoarseness/dysphonia, with women and elderly patients complaining of it more
      frequently; 35.8% of female FP-DPI users > or =65 years of age complained of
      hoarseness/dysphonia. The prevalence of hoarseness/dysphonia was dose dependent
      in patients <65 years old but not in patients > or =65 years of age. Inspiratory
      flow rates adjusted by resistance of the DPIs were not related to the prevalence
      of hoarseness/dysphonia. In patients using ICS, especially in women and the
      elderly patients, who develop hoarseness/dysphonia, it is important to select the
      most suitable device so that patients can continue ICS therapy comfortably.

PMID- 18034975
TI  - Prevalence of type I allergy to natural rubber latex and type IV allergy to latex
      and rubber additives in operating room staff with glove-related symptoms.
AB  - There is lack of data on the prevalence of latex allergy in the health care
      setting in Iran. This study was performed to determine the prevalence of type I
      latex allergy and type IV allergy to latex and rubber additives among the
      operating room staff with glove-related symptoms in 13 general hospitals in
      Tehran. Skin-prick tests with commercial latex extract, patch tests with latex
      and 25 rubber additive series, and total and latex-specific IgE detection were
      performed on the operating room staff who reported latex glove-related symptoms.
      Five hundred twelve self-administered questionnaires (100%) were completed by all
      operating room staff and latex glove-related symptoms were reported by 59 (11.5%)
      employees. Among all symptomatic operating room staff tested, the prevalence of
      type I latex allergy was 30.5% and the prevalence rates of type IV allergy to
      latex and rubber additives were 16.7 and 14.6%, respectively. The most positive
      patch test result with rubber additives was related to tetramethylthiuram
      monosulfide (38.5%). The risk factors for type I latex allergy were female sex (p
      = 0.009) and positive patch test with rubber additives (p = 0.012). Subjects who
      had positive patch test with latex were significantly more likely to have
      positive patch test with rubber additives (p < 0.0001). Our results showed a high
      prevalence of type I latex allergy and type IV allergy to latex and rubber
      additives. Based on this study, we recommend eliminating powdered latex gloves
      from the operating rooms of the 13 studied general hospitals and support the
      substitution of powder-free latex gloves.

PMID- 18034976
TI  - Latex allergy in healthcare workers: an epidemiological study in a Spanish
      hospital.
AB  - To design an effective prevention program in health care workers who are allergic
      to latex it is necessary to know the current epidemiological situation. The
      objectives were to determine the main factors associated with latex allergy and
      to quantify levels of airborne latex particles in different areas of our
      hospital. A cross-sectional study was conducted using a questionnaire completed
      by health care workers. Those who answered the first questionnaire were given a
      second one to fill out and an allergological study (skin-prick test and latex
      specific IgE antibodies) was performed. Latex aeroallergen particles were
      collected with a Quan-tec-air in different areas of the hospital. The first
      questionnaire was sent to 2551 health care workers. Eight hundred forty-one
      (33.14%) subjects returned the completed questionnaire and were given the second
      questionnaire. One hundred fifty-four completed second questionnaire. We
      identified 28 patients who were allergic to latex, and 126 patients who were not
      allergic to latex. In the allergic population there were more nurses aides. More
      allergic patients were found in the Surgery Department, Intensive Care Unit
      (ICU), and Vascular Radiology Unit (VRU). Allergic patients were more likely to
      use a higher number of latex gloves and during more hours than nonallergic
      workers. In the Surgery Department, ICU, VRU, and Laboratory Department more
      pairs of latex gloves were used and during more hours. The medium level of latex
      aeroallergens in 24 determinations in 14 areas of the hospital was 8.12 ng/m3
      (SD, 13.32 ng/m3; range, 0.3-57.7 ng/m3). The higher levels were found in
      Laboratory (n = 2; mean (M) 23; SD, 25.95 ng/m3) and Surgery Departments (n = 11;
      M, 7.43; SD, 16.98 ng/m3; Kruskal Wallis test, p = 0.09). Latex allergy is an
      important health problem for health care workers, especially for those working in
      surgical areas or in those places where more latex gloves are used; in these
      areas higher levels of airborne latex particles are found. We should take into
      account these data to design an effective secondary prevention program.

PMID- 18034977
TI  - Occupational asthma due to esparto hypersensitivity in a building worker.
AB  - Esparto is a gramineous plant that has multiple applications in today's industry.
      Several cases of hypersensitivity pneumonitis (HP) caused by esparto inhalation
      have been reported, but only one case of asthma caused by Aspergillus fumigatus
      contaminating esparto has been communicated. We report a case of asthma induced
      by esparto inhalation in a 58-year-old man, who is a building industry worker,
      with subclinical sensitization to grass pollen. The relation between clinical
      symptoms and work activities was supported by peak expiratory flow (PEF)
      monitorization; PEF values decreased by 20% the days he handled esparto. Prick
      test with esparto was positive. Immunoblot analysis revealed several allergens in
      the esparto extract, some of them present in Lolium and A. fumigatus extracts.
      IgE immunoblot inhibition revealed a complete inhibition of lolium and A.
      fumigatus IgE reactive bands by esparto proteins. The patient then avoided the
      exposure to esparto at work and has remained asymptomatic for the last 2 years.
      In conclusion, this is a case of occupational asthma caused by esparto dust
      mediated by IgE antibodies. Proteins of A. fumigatus as well as proteins from
      this gramineous plant, which cross-reacted with esparto allergens, were
      responsible for the disease.

PMID- 18034978
TI  - Sublingual immunotherapy-induced IL-10 production is associated with changed
      response to the decongestion test: preliminary results.
AB  - Sublingual immunotherapy (SLIT) has been shown to be capable of inducing a
      regulatory T-cell response as evidenced by IL-10 production. Decongestion testing
      consists of spraying an intranasal vasoconstrictor drug to evaluate the recovery
      of nasal airflow limitation. The aim of this study was to assess the association
      of SLIT-induced IL-10 production with nasal airflow recovery after decongestion
      testing. Nineteen patients with perennial allergic rhinitis (PAR) were studied: 9
      patients successfully assumed SLIT for 3 years and 10 patients were considered as
      control. In vitro IL-10 production was evaluated after SLIT. Rhinomanometry and
      decongestion testing were performed in all subjects before and after 3 years.
      After 3 years, SLIT patients showed a significant decrease of nasal resistances
      (0.048) and reduced response to decongestion testing (p = 0.044 for absolute
      values and p = 0.0051 for delta). The comparison with nontreated allergic
      patients shows significant differences concerning both pretest values (p = 0.02)
      and delta percentages (p = 0.00466). In addition, the decrease of nasal airflow
      resistance values and the percentages of reversibility were significantly
      associated with IL-10 levels (p = 0.0016 and p = 0.00294, respectively). This
      preliminary study provides the first evidence of a changed response to
      decongestion testing after SLIT that is associated with IL-10 production in
      patients with PAR.

PMID- 18034979
TI  - Levocetirizine and cytokine production and apoptosis of human eosinophils.
AB  - Antihistamines are a common therapy for allergic symptoms. Eosinophilic
      infiltration is considered a hallmark of allergic inflammation. Eosinophils are
      capable of mediating airway mucosal damage by producing various inflammatory
      mediators including cytokines, chemokines, basic granule proteins, lipid
      mediators, and growth factors. Reduced eosinophil apoptosis is thought to be an
      important feature in the formation of eosinophilia in allergic diseases such as
      allergic rhinitis, atopic eczema, and asthma. The aim of this study was to
      investigate the effects of levocetirizine on the production of inflammatory
      mediators by eosinophils and on eosinophil apoptosis. The production of cytokines
      and other inflammatory mediators by human eosinophils was measured by a cytokine
      antibody array. Apoptosis of isolated human eosinophils was assessed by measuring
      the relative DNA content of propidium iodide-stained cells. Of the 40 cytokines
      studied, levocetirizine (1 microM) was found to enhance the release of tissue
      inhibitor of metalloproteinases 1 and 4, matrix metalloproteinase 9, and heparin
      binding epidermal growth factor and to attenuate the production of interleukins
      (IL)-1 beta and IL-7 and stem cell factor in lipopolysaccharide-stimulated human
      eosinophils. Levocetirizine did not alter constitutive eosinophil apoptosis or
      eosinophil survival induced by IL-5, granulocyte/macrophage colony-stimulating
      factor, tumor necrosis factor alpha, or salbutamol. The results of this study
      suggest that levocetirizine modulates the profile of inflammatory mediators
      including cytokines, growth factors, proteinases, and antiproteinases produced by
      eosinophils, which may be of importance in allergic inflammation and airway
      remodeling. However, eosinophil longevity seems not to be modulated by
      levocetirizine.

PMID- 18034980
TI  - Onset and duration of action of nasal sprays in seasonal allergic rhinitis
      patients: olopatadine hydrochloride versus mometasone furoate monohydrate.
AB  - Rapid relief of symptoms should be one of the primary goals of treatment for
      allergic rhinitis (AR). The onset and duration of action of olopatadine
      hydrochloride nasal spray, 665 mcg (OLO; Patanese), for seasonal AR (SAR) was
      evaluated in this study. This study was performed to determine the onset and
      duration of action of OLO compared with placebo spray, with mometasone furoate
      monohydrate, 50 mcg (MM; Nasonex), as a reference standard. This was a single
      center, single-dose, randomized, double-blinded parallel-group environmental
      exposure chamber study. Patients were primed at two 2-hour priming visits.
      Eligible patients were randomized to OLO, placebo spray, or MM, 2 sprays/nostril.
      Allergy symptoms (sneezing, runny, itchy, and stuffy nose) were rated by patients
      at 16 time points during 12 hours after dosing and patient satisfaction was
      assessed at 4 and 12 hours postdose. Safety was assessed by a review of adverse
      events, cardiovascular and nasal examination parameters. Four hundred twenty-five
      adult patients were randomized. OLO was superior to placebo spray in reducing
      total nasal symptoms (TNSS) within 30 minutes after dosing and maintained
      superiority for at least 12 hours (p < 0.05). The onset of MM was not observed
      until 150 minutes postdose and was smaller in magnitude compared with OLO. OLO
      was superior to both placebo spray (p < 0.0001) and MM (p < 0.05) in patient
      satisfaction. Treatment was well-tolerated with no safety concerns. OLO is
      superior to placebo spray and MM in reducing allergy symptoms; OLO has a rapid
      onset of action and a duration of effect of at least 12 hours.

PMID- 18034981
TI  - Allergy to multiple local anesthetics.
AB  - Real allergy to local anesthetic (LA) is very rare. This study was performed to
      report a case of anaphylaxis to multiple "caine." A 25-years-old atopic nurse
      developed a very severe anaphylactic reaction on her third infiltration for low
      back pain with bupivacaine, lidocaine, and methylprednisolone: she developed a
      vagal reaction, followed during the next 30 minutes by a pruriginous skin rash,
      followed by a tongue edema and a severe bronchospasm. Adrenalin was injected with
      a poor response. She was intubated and transferred to the intensive care unit for
      a few days and, finally, she recuperated completely. Skin-prick tests were done
      on two occasions. In the first session, no reactions were observed with
      triamcinolone and methylprednisolone at 1 mg/cc, but a rapid extending
      maculopapular erythema developed with a final diameter of 50 mm with lidocaine
      0.1% (group 2) and 25 mm with procaine 2% (group 1): control 0 mm, histamine, 3
      mm. She also complained of itchiness in the neck and shoulder, which resolved in
      the next 90 minutes. In the second session, a test with bupivacaine 0.0005%
      (group 2) gave a papule with a diameter of >5 mm, and a test with mepivacaine
      0.001% (group 2) was negative: control, histamine, 3 mm; no subsequent tests with
      mepivacaine were done because she developed a cough and throat pruritus, voice
      modification, and a sensation of throat narrowing, that resolved with treatment.
      We reported a case of anaphylaxis to multiple LA (groups 1 and 2), possibly via
      an IgE-mediated mechanism.

PMID- 18034982
TI  - Perioperative anaphylaxis in a 44-year-old man.
AB  - This article presents a case report of perioperative anaphylaxis in a previously
      nonallergic 44-year-old man undergoing cervical spine surgery. After receiving
      general anesthesia with midazolam, propofol, lidocaine, fentanyl, rocuronium, and
      sevoflurane and cefazolin for prophylaxis, the patient developed hypotension,
      tachycardia, bronchospasm, and generalized erythema. A serum tryptase
      concentration was markedly elevated 2 hours after the anaphylactic episode.
      Initial prick and intradermal skin tests (excluding skin testing for unavailable
      benzylpenicilloyl polylysine) and IgE immunoassays for penicillin and cefazolin
      were negative. However, repeat prick skin testing for cefazolin 6 weeks after
      anaphylaxis was positive. Although anaphylaxis to cephalosporins is rare, it
      remains a potential cause of perioperative anaphylaxis. All cases of
      perioperative anaphylaxis require a workup to identify the offending agent and to
      avoid future reactions. Skin testing regimens for several commonly implicated
      drugs used for general anesthesia are available and are described.

PMID- 18034983
TI  - Ocular cicatrical pemphigoid.

PMID- 18034984
TI  - Complement component 1 inhibitor.

PMID- 18034985
TI  - Flagellated protozoa in cockroaches and sputum: the unhygienic connection?

PMID- 18034986
TI  - High tibial osteotomy for medial compartment osteoarthritis: a comparison of
      clinical and radiological results from closed wedge and focal dome osteotomies.
AB  - This study aimed to evaluate the clinical and radiological results of closed
      wedge osteotomy (11 knees) and focal dome osteotomy (14 knees) in cases of high
      tibial osteotomy undertaken for varus knee with medial compartment
      osteoarthritis. Clinical evaluation was performed using the Knee Society Score
      and no significant difference was seen between the two groups at final follow-up.
      Radiological evaluation was made on the basis of the pre- and postoperative
      mechanical axis, postoperative movement of the tibial axis, loss of correction at
      final follow-up and patellar height measured using the Insall-Salvati index.
      Statistically significant differences were seen with focal dome osteotomy
      compared with closed wedge osteotomy in the InsallSalvati index at final follow
      up, the amount of correction loss and the change in tibial axis location. It is
      concluded that, in the treatment of medial compartment osteoarthritis by high
      tibial osteotomy, focal dome osteotomy is more beneficial than closed wedge
      osteotomy in not creating any additional deformity.

PMID- 18034987
TI  - Treating phenylketonuria: a single centre experience.
AB  - Hyperphenylalaninaemia (HPA) is an inherited disorder that results in raised
      plasma phenylalanine levels with a range of severities, including phenylketonuria
      (PKU). Since the first attempts at treatment using a low-phenylalanine diet and
      after more than 50 years of research, considerable progress has been made so we
      are now at a stage where mental retardation caused by high plasma phenylalanine
      can be prevented. We must, however, be aware of the new challenges we face in
      managing PKU. These include: maintaining optimal growth by providing enough
      phenylalanine without jeopardizing the child's psychomotor development; providing
      an optimal nutritional status that ensures other essential nutrients, such as
      long chain polyunsaturated fatty acids, are not excluded from the diet; ensuring
      optimal compliance to the dietary intervention; and considering patients' quality
      of life. New strategies, such as tetrahydrobiopterin (BH4) supplementation, need
      to be evaluated with regard to safety, efficacy and expected outcomes in specific
      types of HPA.

PMID- 18034988
TI  - Correlation between the in vitro ATP-based chemosensitivity assay and HER2/neu
      expression in women with breast cancer.
AB  - Several in vitro chemosensitivity tests have been developed to predict the
      chemotherapeutic response of tumours prior to initiation of individualized
      treatment for breast cancer. This study investigated whether the in vitro
      chemosensitivity response of cell lines derived from breast cancer patients was
      affected by HER2/neu expression. We cultured breast cancer cell lines from 50
      patients and the adenosine triphosphatebased chemotherapy response assay (ATPCRA)
      was performed with 5-fluorouracil, gemcitabine, docetaxel, doxorubicin,
      methotrexate, vinorelbine and paclitaxel. 5-fluorouracil combined a high median
      cell death rate (32.4%) with the narrowest range of cytotoxic effects (7.3
      65.7%). In addition, gemcitabine showed significantly greater activity in
      HER2/neupositive patients. In contrast, docetaxel was significantly less
      effective in HER2/neu-positive patients. No significant correlation was found
      between the other agents and HER2/neu expression. The use of the ATP-CRA test for
      metastatic tissue from patients with recurrent disease might be a useful approach
      to determine the most effective chemotherapy regimen.

PMID- 18034989
TI  - Antihypertensive efficacy of amlodipine and losartan after two 'missed' doses in
      patients with mild to moderate essential hypertension.
AB  - We compared the effects of amlodipine (5-10 mg, n=94) and losartan (50-100 mg,
      n=94) on the lowering of blood pressure (BP) at steady state and after two missed
      doses, as well as on tolerability. This was a randomized, double-blind study of
      12 weeks of active treatment followed by 2 days of placebo treatment. Twenty-four
      hour ambulatory blood pressure monitoring and office BP measurements were
      performed at baseline, week 12 and after the 2-day drug holiday. After 12 weeks,
      amlodipine was significantly more effective than losartan in reducing both 24-h
      systolic blood pressure (SBP) (-18.0 versus -10.8 mmHg) and diastolic blood
      pressure (DBP) (-10.6 versus -8.0 mmHg). While mean SBP and DBP for both
      treatments increased comparably during the drug holiday, BP values remained
      significantly lower than baseline for both treatments. The superior BP-lowering
      effect of amlodipine compared with losartan was maintained during the drug
      holiday.

PMID- 18034990
TI  - Target-controlled propofol infusion for sedation in patients undergoing
      transrectal ultrasound-guided prostate biopsy.
AB  - The efficacy and safety of the routine use of target-controlled infusion of
      propofol for the sedation of patients undergoing transrectal ultrasound-guided
      prostate biopsy were assessed. The optimal level of sedation was also evaluated.
      A total of 250 patients were randomized into five groups according to sedation
      level determined by the Observer's Assessment of Alertness/Sedation (OAA/S)
      scale. As the level of sedation was increased, the overall pain and discomfort
      score decreased and the satisfaction rate tended to increase, although hypoxia
      meant that intervention occurred more frequently at higher sedation levels.
      Target-controlled infusion of propofol provided safe and effective sedation
      during transrectal ultrasound-guided prostate biopsy, particularly if moderate
      sedation (OAA/S score of 3) was achieved. The effect-site concentration of
      propofol for this level of sedation was about 1.5 microg/ml.

PMID- 18034991
TI  - Mechanisms underlying B-cell tolerance induction by antigen-immunoglobulin G gene
      transfer.
AB  - Previous studies on the mechanisms underlying tolerance induction in diabetes
      have mainly focused on T cells, however B cells also have an important role in
      diabetes. Based on our previous studies that splenocytes, transduced with
      glutamic acid decarboxylase (GAD) 65 fused to immunoglobulin (Ig) G carrier,
      reduced antibody-mediated response in non-obese diabetic (NOD) mice, here we
      examined the mechanisms underlying B-cell tolerance in this system. We found that
      GAD-IgG-transduced splenocytes did not reduce CD40 expression on B-cells in NOD
      mice, but they did downregulate CD40 ligand (CD40L) expression. Furthermore, anti
      CD40L injection reduced autoantibody levels in NOD mice and in vitro experiments
      demonstrated that CD40L blockade reduced the antigenpresenting capability of B
      cells. In conclusion, the results of this study suggest that downregulation of
      CD40L may be one mechanism underlying the induction of B-cell tolerance in GAD
      IgG-treated NOD mice.

PMID- 18034992
TI  - An approach to the detection of lesions in mammograms using fuzzy image
      processing.
AB  - An algorithm was developed in this study, using rule-based fuzzy logic, to enable
      masses that are hard to recognize or detect in mammograms to become more readily
      perceptible. Small lesions, such as microcalcifications and other masses that are
      hard to recognize, especially on film scan mammograms, were processed through
      segmentation. A total of 40 mammograms were used and they were classified by
      radiologists into three groups: those with microcalcifications (n=15), those with
      tumours (n=15), and those with no lesions (n=10). Five mammograms were taken as
      training data sets from each of the groups with microcalcifications and tumours.
      The algorithm was then applied to data not taken for training. The algorithm
      achieved a mean accuracy of 99% compared with the findings of the radiologists.

PMID- 18034993
TI  - Effect of ongoing inflammation in rheumatoid arthritis on P-wave dispersion.
AB  - It has been emphasized recently that there is a strong association between atrial
      fibrillation and inflammation. Rheumatoid arthritis (RA), characterized by
      ongoing inflammatory activity, can increase the risk of atrial arrhythmia. P-wave
      dispersion has been encountered as a risk factor for atrial fibrillation and the
      effect of inflammation on P-wave dispersion has not been studied thoroughly. The
      aim of this study was to examine the effect of ongoing inflammatory activity in
      RA on P-wave dispersion. The study comprised 82 patients diagnosed with RA and 41
      healthy volunteers as controls. Systolic functions of all participants were
      evaluated by echocardiography. Maximum P-wave duration and dispersion were
      calculated and found to be significantly increased in the RA group compared with
      the healthy controls. These parameters were also significantly correlated with C
      reactive protein levels. The findings of this study suggest that RA may be
      associated with increases in P-wave dispersion and maximum P-wave duration, and
      that this association may result from ongoing inflammation.

PMID- 18034994
TI  - Activation of the calcineurin/NFAT signalling cascade starts early in human
      hypertrophic myocardium.
AB  - Cardiac hypertrophy is an independent risk factor for heart failure. Recent
      studies on gene regulation of proteins have involved intracellular Ca2+
      homeostasis. The Ca2+-sensitive phosphatase, calcineurin, is one potential
      regulator of the hypertrophic response, so we aimed to investigate the
      calcineurin-dependent signal pathway at different stages of hypertrophy in human
      myocardium. We found the calcineurin pathway to be significantly activated in
      hypertrophic compared with non-hypertrophic myocardium as demonstrated by
      increased calcineurin activity and expression of calcineurin A-beta and B, and
      GATA-4, and a shift of phosphorylated cytoplasmic NFAT-3 into the nucleus as
      dephosphorylated nuclear NFAT-3. There was a tendency for these changes to be
      more pronounced in the decompensated compared with the compensated hypertrophic
      myocardium. The present study provides evidence for significant activation of the
      Ca2+-triggered calcineurin pathway in hypertrophic humans. Already present in
      compensated hypertrophy it showed a tendency to a further increase following
      transition to decompensated hypertrophy.

PMID- 18034995
TI  - Systemic vanadate ingestion improves early medial collateral ligament repair.
AB  - The medial collateral ligament (MCL) of the knee is frequently injured in sport.
      Repair is slow and often complicated by scar formation which may result in
      impairment of function. Vanadate is a promising efficacious treatment for tissue
      injuries and this study aimed to examine its effect in rats on the histological
      and biomechanical features of MCL healing. Rats received either 0.025 g/kg per
      day vanadate or equivalent amounts of drinking water (control) by intragastric
      gavage for 1 week before and 2 weeks after wounding. Repaired sites were
      dissected out for histological and biomechanical tests 28 days after wounding.
      Fibre bundles in the vanadate-treated group were uniform and evenly spaced.
      Furthermore, vanadate significantly increased the diameter of collagen fibrils in
      the healing tissue. Stiffness and ultimate force of the femur-medial collateral
      ligament-tibia complex for the vanadate-treated group were significantly higher
      than for the controls. The results suggest that vanadate significantly improves
      the histological and biomechanical properties of healing MCL.

PMID- 18034996
TI  - Effective screening of informative single nucleotide polymorphisms using the
      novel method of restriction fragment mass polymorphism.
AB  - Restriction fragment mass polymorphism (RFMP) was applied to pooled DNA for
      selecting informative single nucleotide polymorphisms (SNPs). A total of 225
      coding non-synonymous SNPs (cnSNPs) from immunomodulating genes known to be
      involved in the pathogenesis of asthma were selected from the National Center for
      Biotechnology Information's (NCBI) SNP database (dbSNP). DNA samples from 200
      healthy Koreans were pooled, amplified by polymerase chain reaction, digested
      with restriction enzymes and the fragments analysed by mass spectrometry. Only 30
      of the 225 cnSNPs (13.3%) were informative, i.e.had a minor allele frequency>10%.
      The percentage of informative cnSNPs varied according to the validation status of
      the dbSNP, being 42.3% (22/52) when validated by multiple submissions and
      frequency data, 8.7% (2/23) when validated by multiple submissions alone and 9.1%
      (3/33) when validated by frequency data alone. Most of the 112 unvalidated cnSNPs
      were not informative. In conclusion, the RFMP method using pooled DNA is useful
      in selecting informative SNPs, as also is validation status in the dbSNP.

PMID- 18034997
TI  - Microalbuminuria in Thai essential hypertensive patients.
AB  - Essential hypertensive patients (176 males and 329 females), aged 58.0+/-11.2
      years were enrolled in a cross-sectional study conducted from February to March
      2006 to investigate the prevalence and risk factors for microalbuminuria in
      hypertensive patients attending the Outpatient Department of Siriraj Hospital,
      Bangkok, Thailand. Macroalbuminuria was detected in 11 (2.2%) patients and
      microalbuminuria in 94 (18.6%) patients. Only male aged>or=45 years or female
      aged>or=55 years correlated significantly with a high occurrence of
      microalbuminuria, while calcium channel blocker and statin users were protected
      against microalbuminuria. The presence of microalbuminuria was not associated
      with age>or=60 years, male gender, current/previous smokers, hypertension
      duration>or=10 years, lack of blood pressure normalization, metabolic syndrome,
      use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers,
      and multi-drug use. Risk factor recognition for microalbuminuria will enable
      physicians to identify cases that should be screened for microalbuminuria.

PMID- 18034998
TI  - The cardiovascular safety profile of renzapride, a novel treatment for irritable
      bowel syndrome.
AB  - The cardiac safety of renzapride, a novel benzamide currently under clinical
      development for the treatment of irritable bowel syndrome, was investigated in a
      four-way randomized crossover electrocardiographic clinical study in healthy
      human subjects and also in an in vitro cardiac conductivity study in sheep
      isolated Purkinje fibres. The primary endpoint in the clinical study was
      prolongation of the individually corrected QT interval (QTci). No clinically or
      statistically significant prolongation of QTci after 4 or 20 mg renzapride
      compared with placebo was observed. The relative effects of renzapride and
      cisapride in the in vitro study showed that the cardiac action potential duration
      was unaltered by 0.2 and 2 microM renzapride, shortened by 20 microM renzapride,
      and prolonged by 1 microM cisapride. Cisparide was also a 1000-fold more potent
      inhibitor of human ether-a-go-go related gene (hERG) channels in HEK293 cells
      than renzapride. These studies indicate that therapeutic doses of renzapride are
      unlikely to prolong cardiac action potentials and, therefore, are also unlikely
      to cause cardiac arrhythmias in clinical use.

PMID- 18034999
TI  - Mutation analysis of the Vangl2 coding region revealed no common cause for
      Tetralogy of Fallot.
AB  - Vangl2 (Van Gogh-like 2) protein acts via non-canonical Wnt signalling to
      regulate polarized cell movements during development of the proximal outflow
      tract in vertebrate embryos. Recently, it has been shown that mutations of the
      Vangl2 gene cause aortic arch defects that are characteristic of the loop-tail
      (Lp) mouse and they have also became a strong candidate for causing congenital
      outflow tract defects in humans. Thus, in this study Tetralogy of Fallot (ToF),
      which comprises a group of syndromes that constitutes the most frequent cause of
      congenital cardiac outflow abnormalities in humans, was analysed for mutations
      within all coding regions of the Vangl2 gene. Based on direct sequencing data
      from a combination of 20 patients with ToF and 22 healthy people, three
      polymorphisms have been identified in exon 6 and exon 7 which do not change the
      amino acid sequence. It was concluded, therefore, that there is no specific
      mutation responsible for the ToF phenotype in the Vangl2 gene.

PMID- 18035000
TI  - Effects of Astragalus polysaccharides on chymase, angiotensin-converting enzyme
      and angiotensin II in diabetic cardiomyopathy in hamsters.
AB  - This study investigated the effects of Astragalus polysaccharides (APS), the main
      active extract from the traditional Chinese medicinal herb Astragalus
      membranaceus, on myocardial chymase, angiotensin-converting enzyme (ACE) and
      angiotensin II (Ang II) in diabetic cardiomyopathic hamsters. Plasma levels of
      insulin, C-peptide and glycosylated serum protein (GSP), plasma and myocardial
      levels of Ang II, and myocardial gene expression and activity of chymase and ACE
      were measured after treatment with APS at a dose of 1 g/kg per day or 1 ml of
      normal saline per day (controls) for 10 weeks. GSP levels, myocardial Ang II
      levels, and myocardial gene expression and activity of chymase were significantly
      decreased in diabetic hamsters after treatment with APS compared with controls.
      These results suggest that APS can inhibit the local chymase-Ang II system in
      diabetic cardiomyopathy.

PMID- 18035001
TI  - The effect of chlorogenic acid enriched coffee on glucose absorption in healthy
      volunteers and its effect on body mass when used long-term in overweight and
      obese people.
AB  - The results from a clinical study performed in 12 healthy volunteers with
      different coffee products containing glucose show that instant coffee enriched
      with chlorogenic acid induced a reduction in the absorption of glucose of 6.9%
      compared with the control. No such effects were seen with normal or decaffeinated
      instant coffee. In a second, comparative, randomized, double-blind, 12-week study
      we investigated the effect on the body mass of 30 overweight people, compared
      with normal instant coffee. The average losses in mass in the chlorogenic acid
      enriched and normal instant coffee groups were 5.4 and 1.7 kg, respectively. We
      conclude that chlorogenic acid enriched instant coffee appears to have a
      significant effect on the absorption and utilization of glucose from the diet.
      This effect, if the coffee is used for an extended time, may result in reduced
      body mass and body fat when compared with the use of normal instant coffee.

PMID- 18035002
TI  - Stapled haemorrhoidopexy versus Ferguson haemorrhoidectomy: a prospective study
      with 2-year postoperative follow-up.
AB  - Patients with grade III or IV haemorrhoids underwent stapled haemorrhoidopexy or
      Ferguson haemorrhoidectomy (50 patients in each group) between June 2000 and
      April 2003. Six patients (12.0%) receiving stapled haemorrhoidopexy experienced
      complications: bleeding (2.0%) and haematoma (4.0%); late complications were anal
      fissure (4.0%) and recurrence of haemorrhoidal disease (2.0%). Bleeding was
      treated during the operation by suture ligation and fissures by sphincterotomy;
      haematomas resolved spontaneously with conservative medical treatment. Of those
      undergoing Ferguson haemorrhoidectomy, no bleeding occurred postoperatively,
      however urinary retention was seen in three patients (6.0%) We conclude that
      Ferguson haemorrhoidectomy was safer than stapled haemorrhoidopexy for bleeding
      complications, but stapled haemorrhoidopexy was superior to the Ferguson
      technique in terms of postoperative pain (4.2 versus 7.4 on day 1 after
      operation, decreasing to 2.2 versus 4.2 at 1 week for stapled haemorrhoidopexy
      compared with Ferguson haemorrhoidectomy, respectively), duration of hospital
      stay (92% undergoing stapled haemorrhoidopexy discharged on postoperative day 1)
      and time to return to normal activities (10.0+/-1 versus 28.0+/-2 days,
      respectively).

PMID- 18035003
TI  - Melkersson-Rosenthal syndrome with isolated immunoglobulin E
      hypogammaglobulinaemia.
AB  - Melkersson-Rosenthal syndrome (MRS) is a rare disorder classically presenting
      with a triad of recurrent orofacial swelling, facial palsy and a fissured tongue.
      This case report describes a case of MRS in a patient with isolated
      immunoglobulin E (IgE) hypogammaglobulinaemia. The 52-year-old woman presented
      with puffy eyelids, lower lip swelling and right facial nerve palsy. Fissures of
      the tongue were also noted. On investigation she was found to have a markedly low
      serum IgE level. This case report clearly indicates that IgE-mediated reactions
      do not play a significant role in the development of MRS.

PMID- 18035004
TI  - Bowel perforation secondary to ventriculoperitoneal shunt: case report and
      clinical analysis.
AB  - Bowel perforation is an unusual complication of ventriculoperitoneal shunting.
      This article describes a case of bowel perforation associated with a
      ventriculoperitoneal shunt inserted in an 8-month-old male infant for
      meningocoele and hydrocephalus. Ten months after insertion of the shunt the
      infant presented with the shunting tube protruding through the anus. There were
      no signs of meningitis or peritonitis. At laparotomy the tube was seen to enter
      the transverse colon and was encapsulated by the greater omentum. The tube was
      cut and the distal end removed via the anus. The transverse colon was repaired.
      The catheter continued to function effectively and the patient remained
      asymptomatic. The literature on this rare complication is reviewed and the
      therapeutic options are discussed.

PMID- 18035005
TI  - Ophthalmoplegia with diffuse large B cell lymphoma: vital differential diagnosis.
AB  - Ophthalmoplegia is an unusual finding in diffuse large B cell lymphoma. This
      report describes the case of a 72-year old male patient who presented with
      ophthalmoplegia but no gross neurological manifestations and an isolated mass in
      the left upper thigh. His ophthalmoplegia improved from his first cycle of
      systemic and intrathecal chemotherapy, his thigh mass effusion spontaneously
      resolved, and his laboratory tests also showed improvement. The patient remained
      well, though weak, for several months with no other neurological signs. He
      subsequently died from clinically diagnosed pulmonary embolism.

PMID- 18035006
TI  - Remifentanil and etomidate for laryngeal mask airway insertion.
AB  - Etomidate does not depress the upper airway reflexes, making it difficult to
      insert a laryngeal mask airway (LMA) when using it for anaesthesia. This study
      investigated the effect of adding remifentanil to etomidate for LMA insertion.
      Fifty adult patients, undergoing cystoscopy, were randomized to two groups. The
      propofol-remifentanil group (n=25) received propofol anaesthesia induction (2.5
      mg/kg) and a remifentanil bolus of 0.5 microg/kg, followed by a 2-min
      remifentanil infusion of 0.05 microg/kg per min. The etomidate-remifentanil group
      (n=25) received etomidate anaesthesia induction (0.3 mg/kg) and remifentanil as
      described. The LMA was inserted by a blinded anaesthetist who assessed a number
      of parameters. Only 13 LMAs were inserted at the first attempt in the etomidate
      remifentanil group compared with 23 in the propofol-remifentanil group. Gagging,
      chest rigidity and myoclonus occurred significantly more frequently in the
      etomidate-remifentanil group. We conclude that the addition of remifentanil to
      etomidate anaesthesia induction does not improve LMA insertion.

PMID- 18035007
TI  - An abdominal challenge: the compartment syndrome.

PMID- 18035008
TI  - Liver resection in elderly: comparative study between younger and older than 70
      years patients. Outcomes and implications for therapy.
AB  - BACKGROUND AND AIM: to identify the factors that could influence the outcome of
      the old aged patients underwent liver resection for hepatocellular carcinoma
      (HCC) or colorectal liver metastases (LMCRC). PATIENT AND METHODS: the Authors
      identified 51 patients older 70 years-old over 12-years period underwent
      resection for HCC (n 26) or for LMCRC (n 25). This group was compared with a
      cohort of 93 patients younger than 70 years who underwent resections in the same
      period. We have evaluated the results in terms of peroperative morbidity and
      mortality. RESULTS: the mean age of 51 elderly patients was 74 years-old. Thirty
      five were treated with anatomical resection. Cirrhosis was present in 26 patients
      while 27 had co-morbidities. Thirteen patients developed complications and the
      mean age of these were 76 years compared with 73 of the patients who have not (p=
      .01). No mortality was registered. The cirrhosis, blood transfusions, anatomical
      resection and diameter of the lesion did not influence the outcome. CONCLUSIONS:
      our results indicate the age per se should not be considered a contraindication
      for surgery, that proved to be safe and curative therapy, but showed that old
      age, using 75 years as a cut-off, in association with at least one comorbid
      medical condition could be considered as relevant factor of morbidity.

PMID- 18035009
TI  - Spontaneous ruptured pheochromocytoma: a case report.
AB  - We present a rare case of intra-abdominal hemorrhage due to a ruptured
      pheochromocytoma. Our patient presented with signs of shock. By emergency
      surgery, an hemorrhagic pheochromocytoma of the left adrenal gland was removed.
      Recovery was uneventful. In cases of suspected hemorrhagic pheochromocytoma with
      severe shock, prompt surgery is mandatory and catecholamines administration may
      be crucial to resolve hypotension and guarantee an uneventful recovery.

PMID- 18035011
TI  - [Covered perforation of solitary cecal diverticulum: case report].
AB  - Acute right lower abdominal pain is often clinically difficult to diagnose. The
      diagnosis, especially in young patients, is frequently oriented to appendicular
      disease. Surgical exploration only confirms diagnosis or surprises the surgeon,
      revealing an unexpected right colon diverticulitis. This emergency condition
      challenges the surgeon with the dilemma about the best therapeutic choice:
      conservative or radical treatment? The elective localization of diverticulitis to
      the right colon is very rare (6.6-14%). The authors report a case of covered
      perforation of a solitary cecal diverticulum.

PMID- 18035010
TI  - [Massive lower gastrointestinal bleeding due to diverticular disease during
      antiplatelet therapy. Case report].
AB  - Diverticular disease is very frequent in Western countries; in 5% of the cases it
      is the cause of serious bleeding, haemodynamic instability and death. The authors
      report a case of 74 years old patient with severe lower gastrointestinal
      bleeding. She was in antiplatelet treatment with acetylsalicylic acid (100
      mg/die) and clopidogrel (75 mg/die) for preventing the restenosis of medicated
      stents positioned to treat an acute coronary syndrome. At the same time the
      patient was under treatment for primary hypercholesterolemia with rosuvastatin
      (20 mg/die). The severe haemorrhage demanded haemodynamic stabilization, achieved
      by colloid infusion and blood transfusions. The bleeding continued; selective
      arteriography showed it's origin from the areas of the sigmoid and superior
      hemorrhoidal arteries. During the procedure, embolization of the inferior
      mesenteric artery using spiral type BALT was performed, with consequent bleeding
      interruption. Fifteen days after the embolization, a rectosigmoid colonoscopy
      showed a sigmoid diverticular disease. The treatment with acetylsalicylic acid
      and clopidogrel has surely contributed to the severity of the hemorrhage. Recent
      experimental and clinical evidence suggests a possible antiplatelet effect of the
      statins.

PMID- 18035012
TI  - Peritoneal malignant mesothelioma: case report.
AB  - Our study reports peritoneal diffuse malignant mesothelioma (DMM) in a 43 years
      old male patient, with no exposure to asbestos in his medical history; the
      partner of the patient was also not exposed to asbestos. The exposure to X-rays
      was also excluded. Different pathogenic mechanisms for the pathogenesis of a
      peritoneal diffuse malignant mesothelioma in this patient can be hypothesized,
      for example, SV40 infection and genetic susceptibility; a minimal domestic
      exposure to asbestos can be not excluded. Therefore, further studies in a larger
      number of subjects are necessary to determine whether one or all of these
      hypothetic pathogenic mechanisms are more significant for the development of
      malignant mesothelioma.

PMID- 18035013
TI  - [Repair of umbilical hernia in postmenopausal women].
AB  - The Authors report their personal experience on the employment of the dual-mesh
      in PTFE for the treatment of the umbilical hernias in postmenopausal women. The
      prosthetic repair versus the classic Mayo's technique finds justification for the
      biostructural deficits of the muscolofascial structures of the women in
      menopause, due to the reduction of the ovarian function and made worse from
      previous pregnancies. An evaluation of the trofism of the structures of the
      abdominal wall and the dimensions of the hernias is however indispensable in the
      choice of the prosthetic surgery. In our casuistry the reported morbidity due to
      immediate complications is absolutely negligible. Up to the present, although the
      follow-up is still short, we have not found recurrences.

PMID- 18035014
TI  - An unexpected anatomical variant of the femoral artery in a patient with acute
      lower limb ischemia: case report.
AB  - We report a case of acute embolic ischemia of the right lower limb in a patient
      with unexpected intraoperative anatomic variant of femoral artery. In this
      anomaly, the deep femoral artery arises from the external iliac artery, 2 cm
      above the inguinal ligament, runs with a parallel course with the superficial
      femoral artery, and placed between the branches of femoral nerve. In
      consideration of the difficulty to achieve extensive and optimal control of the
      external iliac artery with the femoral approach, a retrograde embolectomy of the
      iliac artery by two separate arteriotomies on the deep and superficial femoral
      arteries were successfully performed. The literature reviewed about this
      anomalies. In these unexpected intraoperative cases a ductile and ingenious
      approach seems to be mandatory to perform a safe operation with low systemic
      impact.

PMID- 18035015
TI  - [Preliminary results in the use of a new composite prosthesis in incisional
      hernia repair].
AB  - The repair of incisional hernias with the use of prosthetic biomaterials is the
      standard of care today. There are different prosthetic biomaterials that can be
      used to repair incisional hernias. These materials can be divided into products
      that are single component or a combination. Incisional hernia repair using the
      intraperitoneal implantation of a prosthesis requires mesh with impervious
      properties. This is preliminary study with a new composite non resorbable mesh in
      polyethylene terephthalate-polyurethane (HI-TEX PARP MP) used for incisional
      hernia repair in intraperitoneal implantation. This mesh has one permeable side
      in polyethylene terephthalate (PET) for rapid tissue fixation and another side in
      polyurethane (PEU), hydrophobic in order to avoid cell penetration. This is a
      preliminary study of medical records of 24 patients (17 women and 7 men) in whom
      intraperitoneal placement of composite prosthetics in polyethylene terephthalate
      polyurethane (HI-TEX PARP MP) was used between September 2004 and September 2006.
      The incisional hernias were recurrent in 8 patients. The underside of the mesh
      was placed in direct contact with the visceral peritoneum, whereas the upper side
      made contact with the subcutaneous tissue. No intraoperative complications
      occurred. Postoperatively, 1 had seromas, 1 had phlegmon of the wound without
      removing prosthetics. There was 1 death but not dependent of the surgical
      performance. The follow-up, was 12 months (range 1 month-2 years); none had
      discomfort; only one patient had recurrence. Intraperitoneal placement of HI-TEX
      PARP MP has several advantages over other techniques including minimal adhesions,
      a decreased risk of infection and recurrences. In addition this mesh is more
      economics than the other prosthetics in use.

PMID- 18035016
TI  - [Laparoscopic repair of incisional and umbilical hernias. Our experience].
AB  - BACKGROUND: Incisional hernia is a frequent complication of abdominal surgery (2
      20% of all cases). Recurrence rate after simple repair without mesh is very high.
      The use of prosthetic materials has reduced the recurrences. Over the past
      decade, laparoscopic repair of incisional and umbilical hernias has become an
      interesting alternative to open procedure. PATIENTS AND METHODS: The aim of this
      retrospective study was to evaluate efficacy, safety and advantages of
      laparoscopic approach in the treatment of incisional and umbilical hernias. From
      February 2000 through June 2006, a total of 127 incisional hernias (primary and
      recurrent), 21 umbilical and 19 epigastric hernias, were treated by laparoscopic
      approach. The exclusions for laparoscopy were: defect size less than 2 cm or more
      20 cm, anesthesiologic problems, hemocoagulative disorders. The females/males
      ratio was 0/7, with a mean age of 59 years (range 24-83). The abdominal
      associated disease treated were 26. Three cases were treated as urgencies
      (strangulated hernias). RESULTS: The conversion rate was 2 cases (1.2%). Mean
      operative time was 78 min (range 25-170). The mean postoperative hospital stay
      was 2.1 days (range: 1-5). The intra- and postoperative complication rate was 5%
      (above all seromas). The recurrence rate was 1.8% (3 cases). CONCLUSIONS: More
      studies with long-term follow-up are necessary to prove the advantages of
      laparoscopic technique, but this large experience of more than 5 years,
      demonstrates that in selected cases the laparoscopic approach may be an
      interesting and effective alternative to open technique.

PMID- 18035017
TI  - Left atrial myxoma impaction of the left ventricle inflow tract.

PMID- 18035023
TI  - [Goodbye to print medical journals?].

PMID- 18035024
TI  - [Off-label use of biologic agents in the treatment of dermatosis, Part 1:
      infliximab and adalimumab].
AB  - In recent years, the therapeutic armamentarium available to dermatologists has
      been extended thanks to the development of numerous biologic agents. In our
      field, immunomodulators--although currently only approved for psoriasis--have
      given rise to new therapeutic possibilities in a number of inflammatory skin
      diseases. Since these new agents have more specific immunologic mechanisms of
      action, their efficacy and safety is an improvement on traditional
      immunosuppressants. Consequently, it is very likely that they will play an
      important role in dermatology in the next few years. This article, the first part
      of a review of off-label use of biologic agents in dermatology, describes the
      anti-tumor necrosis factor-alpha antibodies, infliximab and adalimumab.

PMID- 18035025
TI  - [Management of basal cell carcinomas with positive margins].
AB  - A common problem in day-to-day practice is the approach to take following
      resection of basal cell carcinoma with positive margins. In such cases, it is
      important to decide whether we should take a wait-and-see approach or consider re
      excision or radiotherapy. To make this decision, 4 key points need to be
      clarified: the significance of positive margins; whether positive margins are
      equivalent to tumor persistence; whether negative margins equate with complete
      excision; and the rate of recurrence in cases of re-excision compared in those in
      which a wait and see approach is taken. Having addressed each of these points,
      the approach will depend on the characteristics of the individual case. Based on
      the evidence presented, an aggressive approach involving re-excision would seem
      indicated in aggressive cases, whereas a flexible strategy combining observation,
      surgery, and radiotherapy (or other treatments) can be used in less aggressive
      cases.

PMID- 18035026
TI  - [Sensitization to gallates: review of 46 cases].
AB  - BACKGROUND: Since 1947, the cosmetics, pharmaceutical, and food industries have
      used gallates as antioxidants to prevent the oxidation of unsaturated fats in
      their products. The aim of this study was to review the cases of sensitization to
      gallates diagnosed in our department between 1985 and 2006. METHODS: All
      suspected cases of allergic contact dermatitis with patch tests positive for
      propyl gallate, octyl gallate, and/or dodecyl gallate were retrieved from the
      database of the allergy section of our dermatology department. RESULTS: Forty-six
      patients had positive patch tests for 1 or more gallates (36 women and 10 men,
      with a mean age of 42.8 years). The most common presenting complaint was
      cheilitis (63% of the cases) followed by dermatitis of the hands (28.26%). The
      most common sensitizing agent was lipstick (54.3%) followed by bakery products
      (15.2%). The test result was considered clinically relevant in 73.9% of the cases
      whereas the relevance was unknown in 23.9 %. CONCLUSIONS: In our case series,
      most patients sensitized to gallates attended the clinic due to cheilitis. The
      main allergen was propyl gallate and the most common mechanism of sensitization
      was use of lipstick. The most common gallate among bakers was octyl gallate. This
      agent was considered to be clinically relevant in all cases studied.

PMID- 18035027
TI  - [Analysis of surgical treatment for nonmelanoma skin cancer performed by
      dermatologists in a public hospital: clinical-pathological correlation, use of
      hospital resources, and waiting list time from diagnosis].
AB  - BACKGROUND: Nonmelanoma skin cancer is the most common form of cancer in humans.
      It can be treated by a variety of specialists and using different techniques,
      surgical excision being the procedure associated with the lowest rates of
      recurrence. No studies have been published addressing differences in the
      management of surgical treatment for nonmelanoma skin cancer according to the
      specialties involved. OBJECTIVES: To assess the preoperative diagnostic accuracy
      and the use of health care resources when surgical treatment of nonmelanoma skin
      cancer is done by dermatologists belonging to the Spanish national health
      service. METHODS: A prospective observational study was carried out over a period
      of 36 months using data corresponding to all patients diagnosed with nonmelanoma
      skin cancer and treated surgically in the Dermatology Department of Complejo
      Hospitalario de Burgos, Spain. Data were analyzed for clinical-pathological
      correlation, complexity of the intervention, use of health care resources, and
      time elapsed between clinical diagnosis and surgery. RESULTS: The study included
      448 patients and 521 skin lesions suspected to be nonmelanoma skin cancer (basal
      cell carcinoma or squamous cell carcinoma). Diagnosis was exclusively clinical in
      487 tumors and a clinical-pathological correlation of 84.39% was observed.
      Surgery was performed with local anesthesia in 96.42% of patients, although 111
      (21.29%) required complex surgical repair. In 349 patients (77.90%) the procedure
      was performed on an outpatient basis, 73 (16.29%) required a short stay in the
      surgical day care unit, and 26 (5.80%) required hospital admission. The mean (SD)
      delay from clinical diagnosis to surgery was 68.44 (42.22) days, with a median
      delay of 60 days. CONCLUSIONS: Dermatology specialists are highly qualified to
      diagnose malignant skin tumors and accurately identify those patients requiring
      surgery. Dermatological surgeons use minimal health care resources, shorten the
      overall length of the process, and help to control overall health care costs for
      cancer.

PMID- 18035028
TI  - [Multiple eruptive dermatofibromas in 2 patients infected with the human
      immunodeficiency virus].
AB  - Multiple eruptive dermatofibromas are an uncommon clinical entity in which
      several lesions appear in a short period of time. Baraf and Shapiro defined them
      in 1970 as the appearance of at least 15 dermatofibromas in a few months. Given
      that incipient cases might be omitted, appearance of 5 to 8 dermatofibromas in 4
      months has been proposed as sufficient to establish diagnosis. Although this
      entity has been reported in healthy subjects, it usually appears with underlying
      autoimmune diseases (lupus erythematosus), human immunodeficiency virus (HIV)
      infection, or treatment with certain drugs. We report 2 cases of multiple
      eruptive dermatofibromas associated with HIV infection. One of these patients was
      unaware of being infected with HIV, and so we believe that the appearance of
      these skin lesions could help early diagnosis of autoimmune diseases or patients
      with immunodepression.

PMID- 18035029
TI  - [Atypical pachydermatous cutaneous course of mastocytosis].
AB  - We describe the case of a 75-year-old man first seen in our department 32 years
      ago for generalized yellowish erythematous papular lesions along with an attack
      of pruritus, tachycardia, and flushing. A diagnosis of urticaria pigmentosa was
      proposed on the basis of these symptoms and the results of skin biopsy. Periodic
      follow-up in the intervening years included serial laboratory analyses, skin
      biopsy, radiological studies, bone scintigraphy, and ultrasound of the liver and
      spleen, with no remarkable findings. The symptoms caused by release of mediators
      decreased progressively. In one of the most recent visits, bone marrow aspirate
      and biopsy were performed, revealing multifocal infiltrates of typical CD117+
      mast cells. Consequently, the hematology department diagnosed indolent systemic
      mastocytosis. A number of marked cutaneous changes were observed during the
      follow-up period: the skin currently appears thickened, indurated, redundant, and
      grayish, with a pachydermatous appearance. This represents an extremely rare form
      of cutaneous involvement in mastocytosis and only 1 case has been described in
      the literature.

PMID- 18035030
TI  - [Erythroderma that spares the major flexion creases].

PMID- 18035031
TI  - [Giant nevus as an aberrant form of von Recklinghausen neurofibromatosis].

PMID- 18035032
TI  - [Dermajazz].

PMID- 18035034
TI  - [Photoaggravated eczema due to promethazine cream].

PMID- 18035035
TI  - [Unilateral contact dermatitis caused by footwear].

PMID- 18035036
TI  - [Two cases of hypertrichosis cubiti].

PMID- 18035037
TI  - [Management of a patient with calciphylaxis and requiring anticoagulation].

PMID- 18035038
TI  - [Melanotic macules of the penis].

PMID- 18035039
TI  - Structure-based interpretation of the mutagenesis database for the nucleotide
      binding domains of P-glycoprotein.
AB  - P-glycoprotein (P-gp) is the most intensively studied eukaryotic ATP binding
      cassette (ABC) transporter, due to its involvement in the multidrug resistance
      phenotype of a number of cancers. In common with most ABC transporters, P-gp is
      comprised of two transmembrane domains (TMDs) and two nucleotide binding domains
      (NBD), the latter coupling ATP hydrolysis with substrate transport (efflux in the
      case of P-gp). Biochemical investigations over the past twenty years have
      attempted to unlock mechanistic aspects of P-glycoprotein through scanning and
      site-directed mutagenesis of both the TMDs and the NBDs. Contemporaneously,
      crystallographers have elucidated the atomic structure of numerous ABC
      transporter NBDs, as well as the intact structure (i.e. NBDs and TMDs) of a
      distantly related ABC-exporter Sav1866. Significantly, the structure of P-gp
      remains unknown, and only low resolution electron microscopy data exists. Within
      the current manuscript we employ crystallographic data for homologous proteins,
      and a molecular model for P-gp, to perform a structural interpretation of the
      existing "mutagenesis database" for P-gp NBDs. Consequently, this will enable
      testable predictions to be made that will result in further in-roads into our
      understanding of this clinically important drug pump.

PMID- 18035040
TI  - Structural characterization of the transmembrane and cytoplasmic domains of human
      CD4.
AB  - Cluster determinant 4 (CD4) is a type I transmembrane glycoprotein of 58 kDa. It
      consists of an extracellular domain of 370 amino acids, a short transmembrane
      region, and a cytoplasmic domain of 40 amino acids at the C-terminal end. We
      investigated the structure of the 62 C-terminal residues of CD4, comprising its
      transmembrane and cytoplasmic domains. The five cysteine residues of this region
      have been replaced with serine and histidine residues in the polypeptide CD4mut.
      Uniformly 15N and 13C labeled protein was recombinantly expressed in E. coli and
      purified. Functional binding activity of CD4mut to protein VpU of the human
      immunodeficiency virus type 1 (HIV-1) was verified. Close to complete NMR
      resonance assignment of the 1H, 13C, and 15N spins of CD4mut was accomplished.
      The secondary structure of CD4mut in membrane simulating dodecylphosphocholine
      (DPC) micelles was characterized based on secondary chemical shift analysis, NOE
      based proton-proton distances, and circular dichroism spectroscopy. A stable
      transmembrane helix and a short amphipathic helix in the cytoplasmic region were
      identified. The fractional helicity of the cytoplasmic helix appears to be
      stabilized in the presence of DPC micelles, although the extension of this helix
      is reduced in comparison to previous studies on synthetic peptides in aqueous
      solution. The role of the amphipathic helix and its potentially variable length
      is discussed with respect to the biological functions of CD4.

PMID- 18035041
TI  - Binding of bovine seminal plasma protein BSP-A1/-A2 to model membranes: lipid
      specificity and effect of the temperature.
AB  - Bovine seminal plasma (BSP) contains a family of phospholipid-binding proteins.
      The affinity of the protein BSP-A1/-A2 for lipid membranes composed of 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and POPC containing 30%
      (mol/mol) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphoethanolamine (POPE) or cholesterol, has been
      investigated by the isothermal titration calorimetry (ITC). This study confirms
      the association of these proteins to lipid bilayers, and provides a direct
      characterization of this exothermic process, at 37 degrees C. The measurements
      indicate that the protein affinity for lipid bilayers is modulated by the lipid
      composition, the lipid/protein ratio, and the temperature. The saturation
      lipid/protein ratio was increased in the presence of cholesterol and, to a lesser
      extent, of phosphatidylethanolamine, suggesting that it is modulated by the lipid
      acyl chain order. For all the investigated systems, the binding of BSP-A1/-A2
      could not be modeled using a simple partitioning of the proteins between the
      aqueous and lipid phases. The existence of "binding sites", and lipid phase
      separations is discussed. The decrease of temperature, from 37 to 10 degrees C,
      converts the exothermic association of the proteins to the POPC bilayers to an
      endothermic process. A complementary 1-D and 2-D infrared spectroscopy study
      excludes the thermal denaturation of BSP-A1/-A2 as a contributor in the
      temperature dependence of the protein affinity for lipid bilayers. The reported
      findings suggest that changes in the affinity of BSP-A1/-A2 for lipid bilayers
      could be involved in modulating the association of these proteins to sperm
      membranes as a function of space and time; this would consequently modulate the
      extent of lipid extraction, including cholesterol, at a given place and given
      time.

PMID- 18035042
TI  - Role of electrostatics in the binding of charged metallophthalocyanines to
      neutral and charged phospholipid membranes.
AB  - Binding of the cationic tetra(tributylammoniomethyl)-substituted hydroxoaluminum
      phthalocyanine (AlPcN(4)) to bilayer lipid membranes was studied by fluorescence
      correlation spectroscopy (FCS) and intramembrane field compensation (IFC)
      methods. With neutral phosphatidylcholine membranes, AlPcN(4) appeared to bind
      more effectively than the negatively charged tetrasulfonated aluminum
      phthalocyanine (AlPcS(4)), which was attributed to the enhancement of the
      coordination interaction of aluminum with the phosphate moiety of
      phosphatidylcholine by the electric field created by positively charged groups of
      AlPcN(4). The inhibitory effect of fluoride ions on the membrane binding of both
      AlPcN(4) and AlPcS(4) supported the essential role of aluminum-phosphate
      coordination in the interaction of these phthalocyanines with phospholipids. The
      presence of negative or positive charges on the surface of lipid membranes
      modulated the binding of AlPcN(4) and AlPcS(4) in accord with the character
      (attraction or repulsion) of the electrostatic interaction, thus showing the
      significant contribution of the latter to the phthalocyanine adsorption on lipid
      bilayers. The data on the photodynamic activity of AlPcN(4) and AlPcS(4) as
      measured by sensitized photoinactivation of gramicidin channels in bilayer lipid
      membranes correlated well with the binding data obtained by FCS and IFC
      techniques. The reduced photodynamic activity of AlPcN(4) with neutral membranes
      violating this correlation was attributed to the concentration quenching of
      singlet excited states as proved by the data on the AlPcN(4) fluorescence
      quenching.

PMID- 18035043
TI  - Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via
      NADPH oxidase 1-dependent superoxide generation.
AB  - Reactive oxygen species (ROS) have important roles in various physiological
      processes. Recently, several novel homologues of the phagocytic NADPH oxidase
      have been discovered and this protein family is now designated as the Nox family.
      We investigated the involvement of Nox family proteins in ionizing irradiation
      induced ROS generation and impairment in immortalized salivary gland acinar cells
      (NS-SV-AC), which are radiosensitive, and immortalized ductal cells (NS-SV-DC),
      which are radioresistant. Nox1-mRNA was upregulated by gamma-ray irradiation in
      NS-SV-AC, and the ROS level in NS-SV-AC was increased to approximately threefold
      of the control level after 10Gy irradiation. The increase of ROS level in NS-SV
      AC was suppressed by Nox1-siRNA-transfection. In parallel with the suppression of
      ROS generation and Nox1-mRNA expression by Nox1-siRNA, ionizing irradiation
      induced apoptosis was strongly decreased in Nox1-siRNA-transfected NS-SV-AC.
      There were no large differences in total SOD or catalase activities between NS-SV
      AC and NS-SV-DC although the post-irradiation ROS level in NS-SV-AC was higher
      than that in NS-SV-DC. In conclusion, these results indicate that Nox1 plays a
      crucial role in irradiation-induced ROS generation and ROS-associated impairment
      of salivary gland cells and that Nox1 gene may be targeted for preservation of
      the salivary gland function from radiation-induced impairment.

PMID- 18035044
TI  - Different immunodominance of HIV-1-specific CTL epitopes among three subtypes of
      HLA-A*26 associated with slow progression to AIDS.
AB  - It is speculated that HLA-A( *)26-restricted HIV-1-specific CTLs can control HIV
      1, since HLA-A( *)26 is associated with a slow progression to AIDS. In three
      major HLA-A( *)26 subtypes, HLA-A( *)2601-restricted, and HLA-A( *)2603
      restricted HIV-1 epitopes have been identified, but HLA-A( *)2602-restricted ones
      have not. We here identified HLA-A( *)2602-restricted HIV-1 epitopes by using
      reverse immunogenetics and compared the immunodominance of the epitopes among the
      three subtypes. Out of 110 HIV-1 peptides carrying HLA-A( *)26 anchor residues,
      only the Gag169-177 peptide, which had been previously identified as an HLA-A(
      *)2601- and HLA-A( *)2603-restricted immunodominant epitope, induced Gag169-177
      specific CD8(+) T cells from only two of six HLA-A( *)2602(+) HIV-1-infected
      individuals. No difference in affinity of this epitope peptide was found among
      these three HLA-A( *)26 subtypes, indicating that Gag169-177 was effectively
      presented by HLA-A( *)2602 but recognized as a subdominant epitope in HIV-1
      infected HLA-A( *)2602(+) individuals. These findings indicate different
      immunodominance of Gag169-177 epitope among 3 HLA-A( *)26 subtypes.

PMID- 18035045
TI  - Nezha, a novel active miniature inverted-repeat transposable element in
      cyanobacteria.
AB  - Miniature inverted-repeat transposable elements (MITEs) were first identified in
      plants and exerted extensive proliferations throughout eukaryotic and archaeal
      genomes. But very few MITEs have been characterized in bacteria. We identified a
      novel MITE, called Nezha, in cyanobacteria Anabaena variabilis ATCC 29413 and
      Nostoc sp. PCC 7120. Nezha, like most previously known MITEs in other organisms,
      is small in size, non-coding, carrying TIR and DR signals, and of potential to
      form a stable RNA secondary structure, and it tends to insert into A+T-rich
      regions. Recent transpositions of Nezha were observed in A. variabilis ATCC 29413
      and Nostoc sp. PCC 7120, respectively. Nezha might have proliferated recently
      with aid from the transposase encoded by ISNpu3-like elements. A possible
      horizontal transfer event of Nezha from cyanobacteria to Polaromonas JS666 is
      also observed.

PMID- 18035046
TI  - Functional studies of the effect of NO donor on human CLCN1 polymorphism/mutants
      expressed in Xenopus laevis oocytes.
AB  - In this study, we investigated the effect of NO donor, diethylamine/nitric oxide
      (DEA/NO), on the electrophysiological behavior of human skeletal muscle chloride
      channel (CLCN1). The wild-type and variants of CLCN1, including one polymorphism
      (P727L) and four mutants (T631I, D644G, G482R, and S471F), were expressed in
      Xenopus oocytes and the ionic current was measured by two-electrode voltage-clamp
      method. Our results revealed that there is no significant difference in the
      current-voltage relationships and half-voltage values of open probability between
      wild-type and variants of CLCN1 except for G482R. Application of the DEA-NO
      (0.1mM) significantly increases the channel conductance of wild-type, T631I,
      D644G, and S471F, but not P727L. This indicates that P727L polymorphism causes
      loss of sensitivity of CLCN1 to the DEA/NO treatment, which could be due to a
      conformational change caused by proline substitution. The data suggest that the
      polymorphic changes may affect the function of CLCN1 in response to the treatment
      of chemical compounds.

PMID- 18035047
TI  - Insulin induces chaperone and CHOP gene expressions in adipocytes.
AB  - Adipocyte secretes bioactive proteins called adipocytokines, and biosynthesis of
      secretory proteins requires molecular chaperones and folding enzymes in
      endoplasmic reticulum (ER). ER chaperones are known to be induced by unfolded
      protein response (UPR) and growth factors, however, it has not been determined
      how ER chaperones expression is regulated in adipocytes. Here we show that
      insulin treatment induced GRP78 and ERO1L mRNA levels in 3T3-L1 adipocytes.
      Insulin also upregulated CHOP mRNA levels, but did not induce phosphorylation of
      eIF2alpha. Pretreatment with insulin protected 3T3-L1 adipocytes against
      thapsigargin-mediated phosphorylation of eIF2alpha but did not against DTT
      mediated one. In vivo mice study showed that GRP78 and CHOP expressions were
      regulated by feeding conditions. These results suggest that insulin signaling is
      important to induce mRNA expressions of GRP78 and CHOP, and may have a protective
      role against UPR.

PMID- 18035048
TI  - Complex formation of p65/RelA with nuclear Akt1 for enhanced transcriptional
      activation of NF-kappaB.
AB  - Akt1 was revealed to interact with Ki-Ras in the cytoplasm of Ki-Ras-transformed
      human prostate epithelial cells, 267B1/K-ras. Moreover, p65/RelA in the nucleus
      was found to interact with both Ki-Ras and Akt1, suggesting the nuclear
      translocation of Akt1:Ki-Ras complex for NF- kappaB activation. In support of
      this, compared with wild type Akt1, the dominant negative Akt1 mutant was
      decreased in its nuclear expression, reducing the Ki-Ras-induced NF-kappaB
      transcriptional activation. Moreover, inhibitors of Ras (sulindac sulfide and
      farnesyltransferase inhibitor I) or PI3K/Akt (wortmannin), reduced the amounts of
      Akt1 and Ki-Ras in the nucleus as well as partial NF-kappaB activity. The
      complete inhibition of Ki-Ras-induced NF-kappaB activation, however, could only
      be obtained by combined treatment with wortmannin and proteasome inhibitor-1.
      Accordingly, clonogenic assay showed Akt1 contribution to IkappaBalpha-mediated
      NF-kappaB activation for oncogenic cell growth by Ki-Ras. Our data suggest a
      crucial role of Ki-Ras:Akt1 complex in NF-kappaB transcriptional activation and
      enhancement of cell survival.

PMID- 18035049
TI  - Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin
      enhanced 5-fluorouracil anticancer activity.
AB  - Although 5-fluorouracil (5-FU) plus leucovorin (LV) is a standard chemotherapy
      regimen for colorectal cancer, the factors that determine the LV-mediated
      enhancement of the antitumor activity of 5-FU have remained unknown. We
      investigated the roles of folylpolyglutamate synthase (FPGS) and gamma-glutamyl
      hydrolase (GGH), which are the main enzymes involved in folate metabolism, in the
      effect of LV. LV enhanced the anticancer activity of 5-FU and the level of
      reduced folate in human colon cancer cells. Small-interfering RNA (siRNA)
      transfected into DLD-1 cells to downregulate FPGS reduced the basal level of
      reduced folate, the folate level after LV treatment, and the enhancement of 5
      fluoro-2'-deoxyuridine (FdUrd)-induced cytotoxicity elicited by LV. By contrast,
      the downregulation of GGH by siRNA increased cellular sensitivity to FdUrd
      combined with LV. These results suggest that FPGS and GGH expression levels in
      tumors are determinants of the efficacy of LV in enhancing the antitumor activity
      of 5-FU.

PMID- 18035050
TI  - Cross-talk among structural domains of human DBP upon binding 25-hydroxyvitamin
      D.
AB  - Serum vitamin D-binding protein (DBP) is structurally very similar to serum
      albumin (ALB); both have three distinct structural domains and high cysteine
      content. Yet, functionally they are very different. DBP possesses high affinity
      for vitamin D metabolites and G-actin, but ALB does not. It has been suggested
      that there may be cross-talk among the domains so that binding of one ligand may
      influence the binding of others. In this study we have employed 2-p-toluidinyl-6
      sulfonate (TNS), a reporter molecule that fluoresces upon binding to hydrophobic
      pockets of DBP. We observed that recombinant domain III possesses strong binding
      for TNS, which is not influenced by 25-hydroxyvitamin D(3) (25-OH-D(3)), yet TNS
      fluorescence of the whole protein is quenched by 25-OH-D(3). These results
      provide a direct evidence of cross-talk among the structural domains of DBP.

PMID- 18035051
TI  - A kinase inhibitor activates the IRE1alpha RNase to confer cytoprotection against
      ER stress.
AB  - Unfolded proteins in the endoplasmic reticulum (ER) cause trans
      autophosphorylation of the bifunctional transmembrane kinase IRE1alpha, inducing
      its RNase activity to splice XBP1 mRNA, in turn triggering a transcriptional
      program in the unfolded protein response (UPR). As we previously showed with the
      yeast IRE1 kinase ortholog, a single missense mutation in the ATP-binding pocket
      of murine IRE1alpha kinase sensitizes it to the ATP-competitive inhibitor 1NM
      PP1, and subordinates RNase activity to the drug. This highly unusual mechanism
      of kinase signaling requiring kinase domain ligand occupancy-even through an
      inhibitor-to activate a nearby RNase has therefore been completely conserved
      through evolution. We also demonstrate that engagement of the drug-sensitized
      IRE1alpha kinase through this maneuver affords murine cells cytoprotection under
      ER stress. Thus kinase inhibitors of IRE1alpha are useful for altering the
      apoptotic outcome to ER stress, and could possibly be developed into drugs to
      treat ER stress-related diseases.

PMID- 18035052
TI  - Ddi1p and Rad23p play a cooperative role as negative regulators in the PHO
      pathway in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the PHO pathway regulates expression of phosphate
      responsive genes such as PHO5, which encodes repressible acid phosphatase
      (rAPase). In this pathway, Pho81p functions as an inhibitor of the cyclin-cyclin
      dependent kinase (CDK) complex Pho80p-Pho85p. However, the mechanism regulating
      the inhibitory activity of Pho81p is poorly understood. Through use of the yeast
      two-hybrid system, we identified the UbL-UbA protein Ddi1p as a Pho81p-binding
      protein. Further, Pho81p levels were found to be low under high-phosphate
      condition and high during phosphate starvation, indicating that Pho81p is
      regulated by phosphate concentration. However, our results revealed that Ddi1p
      and its associated protein Rad23p are not involved in the decrease in Pho81p
      level under high-phosphate condition. Significantly, the Deltaddi1Deltarad23
      strain exhibited a remarkable increase in rAPase activity at an intermediate
      phosphate concentration of 0.4mM, suggesting that Ddi1p and Rad23p play a
      cooperative role as negative regulators in the PHO pathway.

PMID- 18035053
TI  - Crystal structures of HIV-1 reverse transcriptase complexes with thiocarbamate
      non-nucleoside inhibitors.
AB  - O-Phthalimidoethyl-N-arylthiocarbamates (TCs) have been recently identified as a
      new class of potent HIV-1 reverse transcriptase (RT) non-nucleoside inhibitors
      (NNRTIs), by means of computer-aided drug design techniques [Ranise A.
      Spallarossa, S. Cesarini, F. Bondavalli, S. Schenone, O. Bruno, G. Menozzi, P.
      Fossa, L. Mosti, M. La Colla, et al., Structure-based design, parallel synthesis,
      structure-activity relationship, and molecular modeling studies of
      thiocarbamates, new potent non-nucleoside HIV-1 reverse transcriptase inhibitor
      isosteres of phenethylthiazolylthiourea derivatives, J. Med. Chem. 48 (2005) 3858
      3873]. To elucidate the atomic details of RT/TC interaction and validate an
      earlier TC docking model, the structures of three RT/TC complexes were determined
      at 2.8-3.0A resolution by X-ray crystallography. The conformations adopted by the
      enzyme-bound TCs were analyzed and compared with those of bioisosterically
      related NNRTIs.

PMID- 18035054
TI  - Transcriptional mechanism of suppression of insulin gene expression by AMP
      activated protein kinase activator 5-amino-4-imidazolecarboxamide riboside
      (AICAR) in beta-cells.
AB  - It is well known that the activation of AMP-activated protein kinase (AMPK)
      represses insulin gene expression and glucose-stimulated insulin secretion.
      However, how this effect is achieved and the effects of AMPK activation on
      glucolipotoxicity-induced beta-cell dysfunction have not been elucidated. We
      investigate whether BETA2 gene expression are involved in the AMPK-mediated
      regulation of insulin gene expression in normal and dysfunctional beta-cells.
      BETA2 gene expression and protein levels were significantly decreased by AICAR
      treatment and those were associated with the suppression of BETA2 promoter
      activity and DNA binding activity. These results demonstrate that the expressions
      of BETA2 and insulin gene are positively regulated by glucose and negatively by
      AMPK. Therefore, AMPK may function as a key molecule, which conveys extracellular
      metabolic signals into the cells and finely tunes expression of beta-cell
      specific transcription factors in response to glucose level.

PMID- 18035055
TI  - Small dense LDL particles and metabolic syndrome in a sample of middle-aged
      women. Findings from Progetto Atena.
AB  - Metabolic Syndrome (MS) is highly prevalent in the general population. Recently,
      small dense LDL (sd-LDL) particles have been considered a risk marker in MS
      diagnosis. We analyzed cross-sectionally the association between sd-LDL and MS in
      a population-based sample of 210 middle-aged southern Italian women; among them
      86 participants had MS (prevalence 40.9%). LDL particle separation was performed
      by Lipoprint System: seven LDL subfractions were obtained and LDL score (% of sd
      LDL particles) calculated. Women with the MS diagnosis had significantly higher
      LDL score as compared to participants without MS diagnosis (median 0 vs. 3.6,
      p<0.001 by Mann Whitney). The univariate analysis showed a positive and
      significant association between MS diagnosis (OR 4.80; 95% CI 2.29-10.18; p<0.001
      for MS diagnosis) and some MS components Triglycerides (TG), HDL Cholesterol (HDL
      C), (OR 14.82; 95% CI 5.24-41.88; p<0.001 for Ln TG); (OR 0.92; 95% CI 0.89-0.95;
      p<0.001 for HDL-C) and LDL score. Apo B and insulin levels were also positively
      related to the presence of sd-LDL (OR 31.56; 95% CI 5.58-178.29; p<0.001 for apo
      B); (OR 1.07; 95% CI 1.00-1.15; p<0.05 for insulin). After controlling for age,
      insulin and apo B, MS diagnosis (OR 4.0; 95% CI 1.76-9.09; p<0.001 for MS
      diagnosis) and MS components (TG, HDL-C) (OR 4.41; 95% CI 1.22-15.87; p=0.023 for
      Ln TG); (OR 0.94; 95% CI 0.89-0.98; p=0.009 for HDL-C) remained significantly
      associated with high LDL score (upper quintile). Our results suggest that sd-LDL
      particles could be a valuable marker for diagnosis and severity of the MS. Future
      prospective epidemiological studies are envisaged to explore the specific
      contribution of this marker on cardiovascular risk. LDL size measurement could be
      an useful tool for identifying a subsample patients with prominent lipoprotein
      abnormality, within the large population with the MS diagnosis, and who are
      candidates for intensive lipid-lowering interventions.

PMID- 18035056
TI  - Effects of exercise and grape juice ingestion in combination on plasma
      concentrations of purine bases and uridine.
AB  - BACKGROUND: Since grape juice contains considerable amounts of fructose, which
      may increase the plasma concentration of urate, the combination of exercise and
      grape juice may increase the plasma concentration of urate to a greater degree
      than grape juice or exercise alone. METHODS: We performed 3 experiments with 6
      healthy male Japanese. The first was exercise alone (exercise alone experiment),
      the second was grape juice ingestion alone (grape juice alone experiment), and
      the third was a combination of exercise and grape juice ingestion (combination
      experiment). RESULTS: In the exercise alone experiment, the concentrations of
      purine bases and uridine in plasma, and lactate in blood, as well as the urinary
      excretion of oxypurines were increased, whereas the urinary excretion of uric
      acid and fractional excretion of purine bases were decreased. In the grape juice
      alone experiment, the concentrations of purine bases and uridine, as well as
      lactate in blood were increased, whereas the fractional excretion of uric acid
      was decreased. In the combination experiment, the concentrations of purine bases
      and uridine in plasma, and lactate in blood, as well as the urinary excretion of
      oxypurines were increased, whereas the urinary excretion of uric acid and
      fractional excretion of hypoxanthine, xanthine, and uric acid were decreased. The
      increase in plasma concentration of urate by the combination of exercise and
      grape juice was greater than that by each alone, though it was not significantly
      different from the sum of increases in those 2 experiments. CONCLUSION: Increases
      in adenine nucleotide degradation and lactic acid production caused by both
      exercise and grape juice ingestion play an important role in the increase in
      plasma concentration of urate, while those in combination have an additive effect
      on that concentration.

PMID- 18035057
TI  - Total plasma tissue factor pathway inhibitor levels in pre-eclampsia.

PMID- 18035058
TI  - Maternal chronic hepatitis B virus is implicated with low neonatal
      paraoxonase/arylesterase activities.
AB  - BACKGROUND: Paraoxonase/arylesterase activities are closely implicated with liver
      function and antiatherogenetic process. AIM: To evaluate whether maternal chronic
      hepatitis B virus, disease (HBV) affect serum neonatal paraoxonase/arylesterase
      activities. PATIENTS AND METHODS: 28 pregnant women with HBV and 28 healthy
      pregnant women (controls) in the delivery room and their newborns (cord blood)
      underwent laboratory examinations. Serological virus tests and liver function
      tests and paraoxonase (PON 1) activities were measured with the Siemens Advia
      1650 Clinical Chemistry System, while total antioxidant capacity (TAC) levels and
      paraoxonase-arylesterase (PON-aryl) activities were measured
      spectrophotometrically. RESULTS: Serological HBV tests and HBV DNA showed chronic
      HBV (precore mutant G1896A) in the diseased mothers whereas anti-HBc and anti-HBe
      were detected in their neonates. Liver function parameters were found normal in
      controls and both groups of newborns. Moderately increased transaminase levels
      were measured in HBV mothers, whereas TAC levels were decreased in hepatic
      mothers and their newborns. Interestingly albumin levels did not differ among the
      studied groups. PON 1 and PON-aryl activities in the diseased mothers (148+/-14
      U/mL/min, 130+/-16 KU/mL/min) and their infants (32+/-6 U/mL/min, 24+/-5
      KU/mL/min) were significantly lower as compared to those of control mothers
      (217+/-16 U/mL/min, 196+/-14 KU/mL/min p<0.001) and their newborns (57+/-6
      U/mL/min, 48+/-8 UK mL/min p<0.001). Inverse significant correlations were found
      between the studied enzyme activities and liver enzymes in all the groups of
      study except in infants born from HBV mothers and positive with TAC in all the
      studied groups. CONCLUSIONS: Decreased PON 1 and PON-aryl activities were
      measured in infants born from hepatic mothers probably as a consequence of their
      low TAC. Infants born from HBV mothers are at risk for developing LDL oxidation
      perinatally.

PMID- 18035060
TI  - Arp3 is required during preimplantation development of the mouse embryo.
AB  - The role of Arp3 in mouse development was investigated utilizing a gene trap
      mutation in the Arp3 gene. Heterozygous Arp3(WT/GT) mice are normal, however,
      homozygous Arp3(GT/GT) embryos die at blastocyst stage. Earlier embryonic stages
      appear unaffected by the mutation, probably due to maternal Arp3 protein. Mutant
      blastocysts isolated at E3.5 fail to continue development in vitro, lack
      outgrowth of trophoblast-like cells in culture and express reduced levels of the
      trophoblast marker Cdx2, while markers for inner cell mass continue to be
      present. The recessive embryonic lethal phenotype indicates that Arp3 plays a
      vital role for early mouse development, possibly when trophoblast cells become
      critical for implantation.

PMID- 18035059
TI  - Innexins form two types of channels.
AB  - Injury to the central nervous system triggers glial calcium waves in both
      vertebrates and invertebrates. In vertebrates the pannexin1 ATP-release channel
      appears to provide for calcium wave initiation and propagation. The innexins,
      which form invertebrate gap junctions and have sequence similarity with the
      pannexins, are candidates to form non-junctional membrane channels. Two leech
      innexins previously demonstrated in glia were expressed in frog oocytes. In
      addition to making gap junctions, innexins also formed non-junctional membrane
      channels with properties similar to those of pannexons. In addition,
      carbenoxolone reversibly blocked the loss of carboxyfluorescein dye into the bath
      from the giant glial cells in the connectives of the leech nerve cord, which are
      known to express the innexins we assayed.

PMID- 18035061
TI  - VRK3-mediated inactivation of ERK signaling in adult and embryonic rodent
      tissues.
AB  - Vaccinia-related kinase 3 (VRK3), previously characterized as a direct activator
      of vaccinia H1-related (VHR) phosphatase, inactivates extracellular signal
      regulated kinase (ERK) in the nucleus of neuronal cells. Here we show that VRK3
      is expressed in various other rodent tissues and in embryos, and regulates VHR
      phosphatase activity in these tissues. We observed colocalization of VRK3 and VHR
      in the testis tissue and could detect protein complex containing VRK3, VHR and
      ERK in immunoprecipitation analysis. Notably, the addition of recombinant VRK3
      protein to total protein lysates, obtained either from adult tissues or embryos,
      enhanced the phosphatase activity of VHR, but not the activity of MKP3. The
      results further indicate that the VHR-VRK3 complex is a phosphatase-active form.
      In addition, we found that VRK3 can regulate EGF-induced cellular growth
      signaling that is mediated by ERK activation. Our results suggest that in
      addition to neuronal cells, various other rodent adult tissues and embryos
      possess a common signaling mechanism which is involved in an indirect regulation
      of ERK activity by VRK3-mediated VHR activity.

PMID- 18035062
TI  - Myelin glycosphingolipids, galactosylceramide and sulfatide, participate in
      carbohydrate-carbohydrate interactions between apposed membranes and may form
      glycosynapses between oligodendrocyte and/or myelin membranes.
AB  - Glycosphingolipids (GSLs) can interact with each other by homotypic or
      heterotypic trans carbohydrate-carbohydrate interactions across apposed
      membranes, resulting in cell-cell adhesion. This interaction can also provide an
      extracellular signal which is transmitted to the cytosolic side, thus forming a
      glycosynapse between two cells. The two major GSLs of myelin, galactosylceramide
      (GalC) and its sulfated form, galactosylceramide I(3)-sulfate (SGC), are an
      example of a pair of GSLs which can participate in these trans carbohydrate
      carbohydrate interactions and trigger transmembrane signaling. These GSLs could
      interact across apposed oligodendrocyte membranes at high cell density or when a
      membranous process of a cell contacts itself as it wraps around the axon. GalC
      and SGC also face each other in the apposed extracellular surfaces of the
      multilayered myelin sheath. Communication between the myelin sheath and the axon
      regulates both axonal and myelin function and is necessary to prevent
      neurodegeneration. Participation of transient GalC and SGC interactions in
      glycosynapses between the apposed extracellular surfaces of mature myelin might
      allow transmission of signals throughout the myelin sheath and thus facilitate
      myelin-axonal communication.

PMID- 18035063
TI  - Dynamic and electrokinetic behavior of erythrocyte membrane in diabetes mellitus
      and diabetic cardiovascular disease.
AB  - The dynamic and electrokinetic properties of erythrocyte membrane are explored as
      significant indices involved in the association of diabetes and diabetic
      cardiovascular disease. Lipid peroxidation studies reveal malondialdehyde
      concentration to reach a maximum in diabetic cardiovascular patients. Lower
      fluidity of erythrocyte membrane implies declined ability of erythrocyte to
      deform in pathogenic state, which is supported by decreased osmotic resistance.
      Membrane protein profile modification detected by Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) indicates a significant reduction
      in the quantity of ankyrin protein band 2.1 in diabetic subjects. In addition the
      reduction in an immunoreactive band against polyclonal anti-ankyrin antibody
      during Western blot analysis confirms the modification of ankyrin protein in
      diseased erythrocyte (reported for the first time). The electrokinetic behavior
      of erythrocyte membrane is monitored by laser Doppler velocimetry mode of the
      Nano-ZS. Changes in zeta potential values of the red blood cell membrane are
      consistent with decreased membrane fluidity in diseased erythrocytes (reported
      for the first time). Membrane potential values of control, diabetic and diabetic
      cardiovascular erythrocytes are -37.24+/-1.5 mV, -28.44+/-1.34 mV, and -22.21+/
      1.21 mV respectively indicating a gradual lowering of zeta potential when
      erythrocyte membrane undergoes progressive changes - from simple agglomeration to
      fluid gel formation - and finally to a rigid gel.

PMID- 18035064
TI  - TGF-beta up-regulates serum response factor in activated hepatic stellate cells.
AB  - In differentiated smooth muscle cells (SMC) the regulation of SMC marker genes
      (e.g. alpha-smooth muscle actin) is mainly conducted by the serum response factor
      (SRF) and accessory co-factors like myocardin. A number of SMC markers are also
      expressed in activated hepatic stellate cells which are the main cellular
      effectors in liver fibrogenesis. In the present study we found that during
      cellular activation and transdifferentiation the SRF transcription factor is up
      regulated by transforming growth factor-beta, accumulated in the nucleus, and
      exhibited increased DNA-binding activity. These observations were accompanied by
      a forced expression of the SRF co-activator myocardin. Specific targeting of SRF
      by small interference RNA resulted in diminished contents of alpha-smooth muscle
      actin. Therefore, we conclude that hepatic stellate cells retain differentiation
      capacity to evolve characteristics that are typical for cells of the cardiac and
      smooth muscle lineages.

PMID- 18035066
TI  - Metformin therapy in patients with type 2 diabetes complicated by heart failure.

PMID- 18035065
TI  - Ceramide and glucosylceramide upregulate expression of the multidrug resistance
      gene MDR1 in cancer cells.
AB  - In the present study we used human breast cancer cell lines to assess the
      influence of ceramide and glucosylceramide (GC) on expression of MDR1, the
      multidrug resistance gene that codes for P-glycoprotein (P-gp), because GC has
      been shown to be a substrate for P-gp. Acute exposure (72 h) to C8-ceramide (5
      microg/ml culture medium), a cell-permeable ceramide, increased MDR1 mRNA levels
      by 3- and 5-fold in T47D and in MDA-MB-435 cells, respectively. Acute exposure of
      MCF-7 and MDA-MB-231 cells to C8-GC (10 microg/ml culture medium), a cell
      permeable analog of GC, increased MDR1 expression by 2- and 4- fold,
      respectively. Chronic exposure of MDA-MB-231 cells to C8-ceramide for extended
      periods enhanced MDR1 mRNA levels 45- and 390-fold at passages 12 and 22,
      respectively, and also elicited expression of P-gp. High-passage C8-ceramide
      grown MDA-MB-231 (MDA-MB-231/C8cer) cells were more resistant to doxorubicin and
      paclitaxel. Incubation with [1-(14)C]C6-ceramide showed that cells converted
      short-chain ceramide into GC, lactosylceramide, and sphingomyelin. When
      challenged with 5 mug/ml [1-(14)C]C6-ceramide, MDA-MB-231, MDA-MB-435, MCF-7, and
      T47D cells took up 31, 17, 21, and 13%, respectively, and converted 82, 58, 62,
      and 58% of that to short-chain GC. Exposing cells to the GCS inhibitor,
      ethylenedioxy-P4, a substituted analog of 1-phenyl-2-hexadecanoylamino-3
      pyrrolidino-1-propanol, prevented ceramide's enhancement of MDR1 expression.
      These experiments show that high levels of ceramide and GC enhance expression of
      the multidrug resistance phenotype in cancer cells. Therefore, ceramide's role as
      a messenger of cytotoxic response might be linked to the multidrug resistance
      pathway.

PMID- 18035067
TI  - Challenging coronary artery revascularization paradigms.

PMID- 18035068
TI  - Finding the pathway to improving patient outcomes with atherosclerosis imaging:
      who's motivated?

PMID- 18035069
TI  - Using echocardiography in cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy has become a therapeutic option for refractory
      heart failure. Several imaging techniques play an increasingly important role in
      patient selection during and after implantation. This manuscript reviews the
      current echocardiographic techniques available for guiding both patient selection
      and optimization of device programming following implantation.

PMID- 18035070
TI  - How to prevent perioperative myocardial injury: the conundrum continues.
AB  - BACKGROUND: Perioperative myocardial injury (PMI) remains a major cause of
      perioperative morbidity and mortality but clinical strategies to prevent PMI are
      still uncertain. METHODS AND RESULTS: We comprehensively searched PubMed for
      major research articles concerning clinical strategies to prevent PMI. The key
      findings are as follows: (1) the American College of Cardiology/American Heart
      Association guideline update for perioperative cardiovascular evaluation for
      noncardiac surgery is very useful to stratify cardiac risk preoperatively; (2)
      cardiac troponin has emerged as a biomarker to diagnose postoperative PMI and to
      predict clinical outcomes; (3) coronary revascularization before noncardiac
      surgery probably would provide cardiac protection in select patients, especially
      in patients with high-risk coronary artery disease; (4) elective noncardiac
      surgery should be postponed in patients who received coronary stenting recently
      because of high incidence of serious cardiac complications (minimum 6-8 weeks for
      bare metal stents and 6-12 months for drug-eluting stents); and (5) beta-blockers
      and statins are very promising drugs and probably would prevent PMI in a select
      patient population, especially in patients with intermediate risk and stable
      coronary artery disease. CONCLUSIONS: Further studies, especially randomized
      clinical trials and mechanistic investigation are needed to find the best and
      effective clinical strategies to prevent/reduce PMI.

PMID- 18035071
TI  - Rationale and design of a prospective study of the efficacy of a remote
      monitoring system used in implantable cardioverter defibrillator follow-up: the
      Lumos-T Reduces Routine Office Device Follow-Up Study (TRUST) study.
AB  - Increased implantable cardioverter defibrillator (ICD) implant volumes (and
      product advisories/recalls) pose management challenges. Most device
      interrogations at 3- to 6-month routine follow-up visits are "nonactionable,"
      that is, require no clinically significant reprogramming, lead revision, or
      initiation or up-titration of antiarrhythmic medications. Conversely, implanted
      devices collect important diagnostic data (eg, atrial fibrillation onset, system
      integrity) that remain concealed between device interrogations. Remote monitoring
      may resolve some of these challenges, but has not been studied in a large-scale
      clinical trial. Home Monitoring (HM) uses automatic (without patient
      intervention) data and electrogram transmissions with rapid (<24 hours) event
      notification of significant (including silent) events. The Lumos-T Reduces
      Routine Office Device Follow-Up Study (TRUST) is a multicenter, prospective,
      randomized study enrolling 1000 ICD patients designed to test whether HM can
      safely reduce the number of scheduled nonactionable office device interrogations
      by 50% and provide early detection and notification of cardiac and/or device
      problems. After enrollment, TRUST patients are randomized 2:1 to either HM or to
      control (ie, HM off) arms and are seen for an in-office follow-up 3 months
      postimplant. At subsequent 3-month intervals, control patients have conventional
      office visits, whereas in HM, patient data are remotely retrieved and evaluated.
      In HM patients, early notification may automatically occur between periodic
      checks for compromised system integrity (battery, lead parameters, high-voltage
      circuitry) or arrhythmia occurrence (eg, atrial fibrillation, ventricular
      arrhythmia). All study patients will have a final office visit 15 months after
      implant. The results of TRUST may confirm the role of remote monitoring as an
      intensive surveillance mechanism for device management.

PMID- 18035072
TI  - Polymorphisms in hypoxia inducible factor 1 and the initial clinical presentation
      of coronary disease.
AB  - BACKGROUND: Only some patients with coronary artery disease (CAD) develop acute
      myocardial infarction (MI), and emerging evidence suggests vulnerability to MI
      varies systematically among patients and may have a genetic component. The goal
      of this study was to assess whether polymorphisms in genes encoding elements of
      pathways mediating the response to ischemia affect vulnerability to MI among
      patients with underlying CAD. METHODS: We prospectively identified patients at
      the time of their initial clinical presentation of CAD who had either an acute MI
      or stable exertional angina. We collected clinical data and genotyped 34
      polymorphisms in 6 genes (ANGPT1, HIF1A, THBS1, VEGFA, VEGFC, VEGFR2). RESULTS:
      The 909 patients with acute MI were significantly more likely than the 466
      patients with stable angina to be male, current smokers, and hypertensive, and
      less likely to be taking beta-blockers or statins. Three polymorphisms in HIF1A
      (Pro582Ser, rs11549465; rs1087314; and Thr418Ile, rs41508050) were significantly
      more common in patients who presented with stable exertional angina rather than
      acute MI, even after statistical adjustment for cardiac risk factors and
      medications. The HIF-mediated transcriptional activity was significantly lower
      when HIF1A null fibroblasts were transfected with variant HIF1A alleles than with
      wild-type HIF1A alleles. CONCLUSIONS: Polymorphisms in HIF1A were associated with
      development of stable exertional angina rather than acute MI as the initial
      clinical presentation of CAD.

PMID- 18035073
TI  - Matrix metalloproteinase circulating levels, genetic polymorphisms, and
      susceptibility to acute myocardial infarction among patients with coronary artery
      disease.
AB  - OBJECTIVE: The aim of this study was to assess systematic differences between
      patients with acute myocardial infarction (MI) and patients with stable angina in
      matrix metalloproteinase (MMP) circulating levels and genetic polymorphisms.
      METHODS: We identified adults in a large integrated health care delivery system
      whose initial clinical presentation of coronary disease was either an acute MI or
      stable exertional angina. A total of 909 patients with acute MI, 466 patients
      with stable angina, and 1023 healthy older control subjects were genotyped. Serum
      levels of pro-MMP1, MMP2, MMP3, MMP9, and MMP10 were measured in 199 randomly
      selected patients from each group. RESULTS: At a median of 15 weeks after initial
      clinical presentation, higher circulating levels of MMP2 and MMP9 were
      independently associated with acute MI after statistical adjustment for
      conventional risk factors, hs-CRP levels, and cardiac medications. By contrast,
      none of the polymorphisms in MMP1, MMP2, MMP3, MMP9, or MMP10 was significantly
      associated with either acute MI compared with angina, or with coronary disease
      compared with controls. CONCLUSIONS: Circulating levels of MMP2 and MMP9 are
      independently associated with development of an acute MI rather than stable
      angina as the initial clinical presentation of coronary artery disease.

PMID- 18035074
TI  - Association of polymorphisms in platelet and hemostasis system genes with acute
      myocardial infarction.
AB  - BACKGROUND: Genetic polymorphisms may affect the balance between coagulation and
      fibrinolysis and thereby affect individual vulnerability to acute myocardial
      infarction (MI) among patients with underlying coronary atherosclerosis. METHODS:
      We enrolled 1375 patients with an initial clinical presentation of coronary
      disease. We genotyped 49 single nucleotide polymorphisms (SNPs) in 9 coagulation
      system genes and compared patients who had an initial acute MI with patients who
      presented with stable exertional angina. RESULTS: An SNP in CD36 (rs3211956) was
      significantly (P = .04) more common among patients who presented with acute MI
      (minor allele frequency 10.5%) than patients with stable exertional angina (minor
      allele frequency 8.0%). This association became marginally significant, however,
      after adjustment for conventional cardiac risk factors in an additive genetic
      model (odds ratio 1.34, CI 1.00-1.88, P = .053). An SNP in ITGB3 (Leu59Pro,
      rs5918) was slightly, but not significantly (P = .083), more common among
      patients with acute MI (minor allele frequency 14.5%) than among patients with
      stable exertional angina (minor allele frequency 12.0%). Two linked SNPs in THBD
      (Ala473Val, rs1042579; and rs3176123) were slightly, but not significantly (P =
      .079 and 0.052, respectively), less common among patients with acute MI (minor
      allele frequency 16.1%) than among patients with stable exertional angina (18.7%
      and 19.0%, respectively). CONCLUSIONS: Four SNPs in platelet glycoprotein and
      hemostatic genes were nominally associated with acute MI rather than stable
      exertional angina as the initial clinical presentation of coronary artery
      disease. These findings are suggestive but require independent confirmation in
      larger studies.

PMID- 18035075
TI  - Do plasma biomarkers of coagulation and fibrinolysis differ between patients who
      have experienced an acute myocardial infarction versus stable exertional angina?
AB  - BACKGROUND: Circulating concentrations of proteins associated with coagulation
      and fibrinolysis may differ between individuals with coronary artery disease
      (CAD) who develop an acute myocardial infarction (AMI) rather than stable
      exertional angina. METHODS: We compared plasma concentrations of fibrinogen, d
      dimer, tissue-type plasminogen activator, and plasminogen activator inhibitor-1
      (PAI-1) between patients whose first clinical manifestation of CAD was an AMI (n
      = 198) rather than stable exertional angina (n = 199). We also compared plasma
      concentrations of these proteins between patients with symptomatic CAD (either
      AMI or stable angina; n = 397) and healthy, control subjects (n = 197) to confirm
      the sensitivity of these assays to detect epidemiologic associations. RESULTS: At
      a median of 15 weeks after presentation, patients with AMI had slightly higher d
      dimer concentrations than patients with stable angina (P = .057), but were not
      significantly different in other markers. By contrast, fibrinogen, d-dimer, and
      tissue-type plasminogen activator were significantly higher (P < .001) and PAI-1
      lower in patients with CAD than in healthy control subjects. After statistical
      adjustment for clinical covariates, cardiac risk factors, medications, and other
      confounders, fibrinogen, d-dimer, and PAI-1 remained significantly associated
      with CAD. CONCLUSION: Selected plasma markers of coagulation and fibrinolysis did
      not distinguish patients presenting with AMI from those with stable exertional
      angina.

PMID- 18035076
TI  - Percutaneous coronary intervention for late reperfusion after myocardial
      infarction in stable patients.
AB  - BACKGROUND: Results of randomized trials that have compared mechanical coronary
      artery recanalization versus medical therapy for total occlusion late after
      myocardial infarction (MI) have been conflicting. METHODS: We performed a meta
      analysis of randomized trials comparing percutaneous coronary intervention (PCI)
      with medical therapy in stable patients with an occluded artery 1 to 45 days
      after MI. Six trials and one substudy were included with data on 2617 patients
      for the clinical outcomes and 653 patients for determination of ejection fraction
      (EF) during follow-up. Outcomes included death, MI, death or MI, congestive heart
      failure (CHF), and change in left ventricular EF. RESULTS: There were no
      statistically significant differences for any clinical outcome, with trends for
      an increase in MI (risk ratio 1.26, P = .19) and decrease in CHF (risk ratio
      0.67, P = .19) in the PCI arm. The PCI arm showed a slight superiority in left
      ventricular EF (2%, 95% CI 0.1%-2.8%). Early smaller studies showed formally
      statistically significant benefits for CHF and EF, but the much larger Occluded
      Artery Trial and Total Occlusion Study of Canada 2 found no benefit. For CHF, the
      difference between early smaller studies and Occluded Artery Trial was beyond
      chance (P = .02). CONCLUSIONS: Percutaneous coronary intervention does not seem
      to confer any benefits when used for late revascularization of occluded arteries
      after MI in stable patients.

PMID- 18035077
TI  - Does detection of carotid plaque affect physician behavior or motivate patients?
AB  - BACKGROUND: Imaging techniques to identify subclinical atherosclerosis are
      becoming more widespread, but few data exist regarding their influence on patient
      or physician behavior. We evaluated the impact of ultrasound screening to
      identify carotid artery plaques on physician treatment plans and patient
      motivation. METHODS: Subjects included asymptomatic patients without known
      vascular disease who had 2 or more cardiac risk factors. Circumferential scanning
      of the right and left carotid arteries to identify carotid plaques was performed
      using a handheld ultrasound device in an office setting. The physician's initial
      treatment recommendations were assessed before and after the results of the
      carotid scan were reported. Subjects completed a survey to assess motivation to
      make lifestyle changes before and after the results of the scan were provided.
      RESULTS: Fifty subjects were enrolled over 9 months. Their mean (SD) age was 54.0
      (10.4) years and their mean Framingham 10-year cardiovascular risk was 7.8%
      (7.9%). More than half (58%) of the subjects had at least one carotid plaque.
      When carotid plaque was identified, physicians were more likely to prescribe
      aspirin (P = .031) and lipid-lowering therapy (P = .004). Although subjects with
      carotid plaque reported an increase in their perceived likelihood of developing
      heart disease (P = .013), they did not report increased motivation to make
      lifestyle changes. CONCLUSIONS: Ultrasound screening for carotid plaque in an
      office setting can alter physician treatment plans. Although the presence of
      plaque increased patient perception of cardiovascular risk, it did not motivate
      patients to make lifestyle changes.

PMID- 18035078
TI  - Effect of enoxaparin versus unfractionated heparin in diabetic patients with ST
      elevation myocardial infarction in the Enoxaparin and Thrombolysis Reperfusion
      for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction
      study 25 (ExTRACT-TIMI 25) trial.
AB  - BACKGROUND: Patients with diabetes mellitus (DM) are at higher risk for
      complications after ST-elevation myocardial infarction (STEMI) than patients
      without DM. Potent antithrombotic therapies may offer particular benefit for
      these high-risk patients and must be balanced against the potential for increased
      bleeding. METHODS: We performed a prospectively planned analysis of efficacy and
      safety in patients with DM among 20,479 patients with STEMI treated with
      fibrinolysis and randomized to a strategy of enoxaparin (up to 8 days) or
      unfractionated heparin (UFH) (48 hours) in ExTRACT-TIMI 25. RESULTS: Patients
      with DM (n = 3060) were older and more likely to be women and to present with
      heart failure (P < .0001 for each) than those without DM. After adjustment for
      the TIMI Risk Score, sex, and renal function, patients with DM were at 30% higher
      risk for death or myocardial infarction (MI) by 30 days (OR(adj) 1.29, 95% CI
      1.14-1.46). Among patients with DM, the enoxaparin strategy reduced mortality
      (9.5% vs 11.8%, relative risk [RR] 0.81, 95% CI 0.66-0.99), death/MI (13.6% vs
      17.1%, RR 0.80; 95% CI 0.67-0.94), and death/MI/urgent revascularization (16.0%
      vs 19.7%, RR 0.81, 95% CI 0.70-0.94). The enoxaparin strategy was associated with
      a trend toward higher major bleeding (2.6% vs 1.6%, RR 1.63, 95% CI 0.99-2.69).
      Taking efficacy and safety into account, the enoxaparin strategy offered superior
      net clinical benefit (death/MI/major bleed, 14.8% vs 18.0%, RR 0.83, 95% CI 0.70
      0.97) compared with UFH in patients with DM. CONCLUSIONS: In a subgroup analysis,
      a reperfusion strategy including enoxaparin significantly improved outcomes
      compared with UFH among high-risk STEMI patients with DM undergoing fibrinolysis.

PMID- 18035079
TI  - Adjunctive benefits from low-molecular-weight heparins as compared to
      unfractionated heparin among patients with ST-segment elevation myocardial
      infarction treated with thrombolysis. A meta-analysis of the randomized trials.
AB  - BACKGROUND: Improvement in adjunctive antithrombotic therapy is a key point in
      pharmacologic reperfusion for ST-segment elevation myocardial infarction (STEMI).
      The aim of the current study was to perform an updated meta-analysis of all
      randomized trials comparing low-molecular-weight heparins (LMWHs) versus
      unfractionated heparin (UFH) in patients with STEMI treated with thrombolysis.
      METHODS: We obtained results from all randomized trials comparing LMWHs versus
      UFH among patients with STEMI treated with thrombolysis. The literature was
      scanned by formal searches of electronic databases (MEDLINE and CENTRAL) from
      January 1990 to June 2007. The following keywords were used: randomized trial,
      myocardial infarction, reperfusion, thrombolysis, duteplase, reteplase,
      tenecteplase, alteplase, UFH, LMWHs, dalteparin, nadroparin, enoxaparin,
      reviparin, parnaparin. Clinical end points assessed were mortality and
      reinfarction at 30-day follow-up, whereas major bleeding complications were
      assessed as safety end point. The relationship between mortality benefits from
      LMWHs and patient's risk profile was evaluated by using a weighted least-square
      regression in which results from each trial were weighted by the square root of
      the number of patients in each trial. No language restriction was applied.
      RESULTS: We identified a total of 8 randomized trials, including 13,940 patients
      randomized to LMWHs and 13,818 to UFH. Low-molecular-weight heparins were
      associated with a trend in reduction in mortality (6.6% vs 7.2%, odds ratio [OR]
      0.92, 95% CI 0.84-1.01, P = .08, P heterogeneity [P het] = 0.7) and significant
      reduction in reinfarction (3.2% vs 4.8%, OR 0.65, 95% CI 0.58-0.64, P < .0001, P
      het = 0.39), but a higher risk of major bleeding complications (2.4% vs 1.8%, OR
      1.37, 95% CI 1.16-1.61, P < .001, P het = 0.32). CONCLUSIONS: Among patients with
      STEMI treated with thrombolysis, LMWHs, as compared to UFH, are associated with a
      trend in mortality benefits and a significant reduction in reinfarction (reMI) at
      30-day follow-up, but with higher risk of major bleeding complications. In view
      of the additional practical advantages, such as reduced interindividual
      variability in therapeutic response and no need for frequent activated partial
      thromboplastin time (aPTT) monitoring and dose adjustment, LMWHs should be
      considered, instead of UFH, among patients with STEMI treated with thrombolysis.

PMID- 18035080
TI  - The relationship between the initiation of antimicrobial therapy and the
      incidence of stroke in infective endocarditis: an analysis from the ICE
      Prospective Cohort Study (ICE-PCS).
AB  - BACKGROUND: Embolic events to the central nervous system are a major cause of
      morbidity and mortality in patients with infective endocarditis (IE). The
      appropriate role of valvular surgery in reducing such embolic events is unclear.
      The purpose of this study was to determine the relationship between the
      initiation of antimicrobial therapy and the temporal incidence of stroke in
      patients with IE and to determine if this time course differs from that shown for
      embolic events in previous studies. METHODS: Prospective incidence cohort study
      involving 61 tertiary referral centers in 28 countries. Case report forms were
      analyzed from 1437 consecutive patients with left-sided endocarditis admitted
      directly to participating centers. RESULTS: The crude incidence of stroke in
      patients receiving appropriate antimicrobial therapy was 4.82/1000 patient days
      in the first week of therapy and fell to 1.71/1000 patient days in the second
      week. This rate continued to decline with further therapy. Stroke rates fell
      similarly regardless of the valve or organism involved. After 1 week of
      antimicrobial therapy, only 3.1% of the cohort experienced a stroke. CONCLUSIONS:
      The risk of stroke in IE falls dramatically after the initiation of effective
      antimicrobial therapy. The falling risk of stroke in patients with IE as a whole
      precludes stroke prevention as the sole indication for valvular surgery after 1
      week of therapy.

PMID- 18035081
TI  - C-reactive protein, bezafibrate, and recurrent coronary events in patients with
      chronic coronary heart disease.
AB  - BACKGROUND: Elevated C-reactive protein (CRP) levels are related to increased
      coronary risk in healthy subjects and in patients with acute coronary syndromes.
      The aims of the present study were to assess the following: (1) the association
      between CRP and subsequent coronary risk in patients with chronic coronary heart
      disease (CHD), (2) the effect of long-term bezafibrate treatment on CRP levels,
      and (3) to evaluate the consequences of change in CRP level over time on
      subsequent risk. METHODS: Patients with chronic CHD (n = 3122) were recruited to
      a secondary prevention study that assessed the efficacy of bezafibrate versus
      placebo. C-reactive protein was measured in plasma samples collected at
      prerandomization and after 2 years of follow-up. Mean follow-up time was 6.2
      years. Primary end point was fatal and nonfatal myocardial infarction and sudden
      cardiac death. RESULTS: Increased baseline CRP levels were associated with
      increased risk (hazard ratios [HRs] per unit of log-transformed CRP level change)
      of myocardial infarction (HR 1.17, 95% CI 1.03-1.33), the primary end point (HR
      1.19, 95% CI 1.06-1.34), total death (HR 1.19, 95% CI 1.02-1.40) and cardiac
      death (HR 1.28, 95% CI 1.04-1.59). After 2 years, CRP levels increased by 3.0%
      (from a mean level of 3.44 mg/L) in the bezafibrate group and by 3.7% (from 3.49
      mg/L) in the placebo group. C-reactive protein levels after 2 years were
      associated with increased subsequent cardiovascular risk. CONCLUSIONS: Baseline
      CRP and 2-year CRP levels were associated with subsequent risk of myocardial
      infarction and death in patients with chronic CHD. Bezafibrate did not reduce CRP
      levels as compared with placebo.

PMID- 18035082
TI  - Clinical presentation and investigation findings in cardiac myxomas: new insights
      from the developing world.
AB  - BACKGROUND: Cardiac myxomas are an uncommon condition and most of the available
      information on their clinical features comes from smaller series of patients from
      developed countries. Our aim was to quantify and correlate the clinical and
      investigation findings in cardiac myxomas in a developing country and compare
      them with existing data. METHODS: A retrospective study of case notes,
      electrocardiograms, and x-rays of 171 patients treated for cardiac myxoma from
      February 1992 to October 2006 at a large charitable institution in South India
      was conducted. Frequency of different clinical findings and relationships between
      these findings, age, sex, tumor location, and size were calculated. RESULTS: The
      mean age at presentation was 37.1 years. Dyspnea was the most common symptom.
      Embolism was found in 9% of patients and systemic symptoms in 20% of patients.
      Auscultation abnormalities were present in 89% of patients, including a tumor
      plop in 50%. Left atrial enlargement was the most common electrocardiographic
      abnormality (35%), whereas cardiomegaly was the most common chest x-ray finding
      (55%). Raised erythrocyte sedimentation rate was found in 75% and anemia in 45%
      of patients. Female patients and patients with right atrial myxomas more commonly
      had systemic symptoms. Tumor size correlated with electrocardiographic and x-ray
      abnormalities. CONCLUSIONS: Cardiac myxomas present at a younger age in
      developing countries. Almost all patients were symptomatic because they presented
      for medical care at an advanced stage of disease. Certain clinical manifestations
      depend on site and size of the tumor as well as age of the patient. A high index
      of suspicion is necessary for making an early diagnosis.

PMID- 18035083
TI  - Optimal medical therapy at discharge in patients with acute coronary syndromes:
      temporal changes, characteristics, and 1-year outcome.
AB  - BACKGROUND: There are limited data on the recent trend in the use of optimal
      evidence-based medical therapies after acute coronary syndromes (ACSs). We sought
      to evaluate (1) the temporal changes in medical management of patients discharged
      after an ACS; (2) patient and practice characteristics associated with optimal
      medical therapy at discharge; and (3) the association between discharge
      medication use and 1-year outcome. METHODS: The Canadian ACS I (September 1999
      June 2001) and ACS II (October 2002-December 2003) Registries were prospective,
      multicenter, observational studies of 6853 patients admitted for ACS. We examined
      the discharge use of medications among 5833 hospital survivors who did not have
      any contraindications to antiplatelet/anticoagulant, beta-blocker, angiotensin
      converting enzyme inhibitor, or lipid-modifying therapies. Optimal medical
      therapy was defined as the use of all indicated medications. Follow-up data at 1
      year were collected by telephone interview. We performed hierarchical logistic
      regression to identify patient characteristics and care patterns associated with
      optimal medical treatment and to examine its relationship with 1-year mortality.
      RESULTS: There were significant increases in the discharge use of all 4 classes
      of medications over time; 28.9% and 51.8% of patients in ACS I and ACS II
      Registries, respectively, were prescribed optimal medical therapy (P < .001).
      Advanced age, female sex, prior heart failure, renal dysfunction, and coronary
      bypass surgery during hospitalization were negative independent predictors of
      optimal medical therapy. Conversely, enrollment in ACS II Registry, history of
      dyslipidemia, presence of ST elevation and abnormal cardiac biomarker, previous
      myocardial infarction, and previous coronary revascularization were independently
      associated with the use of combination therapy. After adjusting for other
      validated prognosticators, patients receiving optimal medical therapy had
      significantly lower 1-year mortality (adjusted odds ratio 0.54, 95% confidence
      interval 0.36-0.81, P = .003) compared with those given 0 or 1 drug at discharge.
      Over the 1-year follow-up period, substantial numbers of patients discontinued
      therapies, whereas others were initiated on treatment. CONCLUSIONS: Despite the
      temporal increases in the combined use of evidence-based pharmacologic therapies,
      which is associated with improved outcome, medical management of ACS remains
      suboptimal. Quality improvement strategies are needed to enhance the appropriate
      use of effective therapies, targeting specifically the high-risk but undertreated
      patients who may derive the greatest therapeutic benefit.

PMID- 18035084
TI  - Coronary dominance and prognosis of patients with acute coronary syndrome.
AB  - BACKGROUND: A number of studies have identified the number of diseased vessels to
      be an important determinant of survival in patients with acute coronary syndrome
      (ACS). It is unknown if coronary dominance has an impact on prognosis of these
      patients. We hypothesized that the prognosis of patients with ACS with left
      dominance (LD) would be worse than that of patients with right or mixed
      dominance. METHODS: The study population consisted of 27,289 patients whose
      primary indication for cardiac catheterization was ACS. The patients were divided
      into 3 groups according to coronary dominance. The mean duration of follow-up was
      3.5 years (range 1-6.5 years). A Cox proportional hazards analysis was used to
      compare survival by dominance, adjusting for age, sex, diagnosis, comorbidities,
      severity of coronary disease, and ejection fraction. RESULTS: The rates and
      patterns of revascularization among patients with significant coronary disease
      were similar between the groups. At the end of follow-up, patients with LD had a
      significantly higher mortality (hazard ratio 1.18, 95% CI 1.05-1.34; adjusted
      hazard ratio 1.13, CI 1.00-1.28). The mortality of patients with mixed and right
      dominance was similar. CONCLUSION: In patients with ACS, LD is a significant and
      independent predictor of increased long-term mortality. Further research is
      needed to determine mechanisms of increased mortality in patients with LD and
      measures that can be taken to improve the outcome of patients with left-dominant
      circulation.

PMID- 18035085
TI  - Glutamate-cysteine ligase polymorphism, hypertension, and male sex are associated
      with cardiovascular events. Biochemical and genetic characterization of Italian
      subpopulation.
AB  - BACKGROUND: Glutathione (GSH) is an important intravascular scavenger that
      protects endothelial cells from atherosclerosis. However, it is still unknown
      whether cardiovascular (CV) events are associated with metabolic and genetic
      factors, linked to GSH synthesis in an Italian subpopulation, and if a glutamate
      cysteine ligase polymorphism within the catalytic subunit (GCLC) could affect
      blood and plasma GSH concentrations. METHODS: One hundred subjects, with or
      without CV risk factors, were enrolled to evaluate plasma and erythrocyte redox
      status (GSH, homocysteine, cysteine, cysteinylglycine), antioxidant vitamins
      (alpha-tocopherol and ascorbate), malondialdehyde, a lipid peroxidation product,
      and the presence of the GCLC-129 C/T polymorphism; an experimental
      hyperhomocysteinemia after methionine-induced stimulation of transsulfuration
      pathway was performed in 91% of enrolled subjects. Clinical, biochemical, and
      genetic variables were correlated with the presence of CV events (myocardial
      infarction, transient ischemic attacks, and stroke). RESULTS: By multiple
      logistic regression analysis, male sex (P = .027), hypertension (P = .001), and
      GCLC C/T genotype (P = .009) were the only variables associated with events.
      Plasma alpha-tocopherol content decreased postmethionine in the T allele subjects
      compared with wild type (P for time x group interaction = .001). Plasma-reduced
      GSH level was higher in C/T than in C/C genotype subjects at both time points (P
      for group = .03), whereas intracellular GSH concentration did not differ between
      the 2 genotype groups either at baseline or postmethionine. CONCLUSIONS: GCLC T
      allele, together with hypertension and male sex, is associated with CV events in
      our study population. Moreover, after stimulation of transsulfuration,
      intracellular GSH content is preserved in T allele subjects, probably by
      increases in GSH turnover and export, and consumption of alpha-tocopherol.

PMID- 18035086
TI  - High yield of LMNA mutations in patients with dilated cardiomyopathy and/or
      conduction disease referred to cardiogenetics outpatient clinics.
AB  - BACKGROUND: Among the most frequently encountered mutations in dilated
      cardiomyopathy (DCM) are those in the lamin A/C (LMNA) gene. Our goal was to
      analyze the LMNA gene in patients with DCM and/or conduction disease referred to
      the cardiogenetics outpatient clinic and to evaluate the prevalence of LMNA
      mutations and their clinical expression. METHODS AND RESULTS: The LMNA gene was
      screened in 61 index patients. Eleven mutations (including 6 novel) were
      identified, mainly in the subgroup of familial DCM with cardiac conduction
      disease (3/10 index patients) and in patients with DCM and Emery-Dreifuss, Limb
      Girdle, or unclassified forms of muscular dystrophy (7/8 index patients). In
      addition, a mutation was identified in 1 of 4 families with only cardiac
      conduction disease. We did not identify any large deletions or duplications.
      Genotype-phenotype relationships revealed a high rate of sudden death and cardiac
      transplants in carriers of the p.N195K mutation. Our study confirmed that the
      p.R225X mutation leads to cardiac conduction disease with late or no development
      of DCM, underscoring the importance of this mutation in putative familial "lone
      conduction disease." Nearly one third of LMNA mutation carriers had experienced a
      thromboembolic event. CONCLUSIONS: This study highlights the role of LMNA
      mutations in DCM and related disorders. A severe phenotype in p.N195K mutation
      carriers and preferential cardiac conduction disease in p.R225X carriers was
      encountered. Because of the clinical variability, including the development of
      associated symptoms in time, LMNA screening should be considered in patients with
      DCM or familial lone conduction disease.

PMID- 18035087
TI  - Effects of statin therapy on preventing atrial fibrillation in coronary disease
      and heart failure.
AB  - BACKGROUND: Statins are associated with decreased incidence of life-threatening
      arrhythmias in patients with cardiomyopathy and reduce death and hospitalization
      in congestive heart failure (CHF). We hypothesized that statin use will reduce
      incident atrial fibrillation (AF) in patients with coronary heart disease (CHD),
      including those with CHF. METHODS: A cohort of 17,741 patients with CHD examined
      between 1994 and 1997 at 5 Veterans Affairs medical facilities was assembled.
      Patients with known AF, warfarin treatment, liver disease, or no follow-up visits
      were excluded. The final cohort included 13,783 patients. The primary outcome was
      time to development of AF. Propensity scores were used to balance statin-treated
      and untreated patients with respect to baseline characteristics. Time from the
      initial visit to development of AF was analyzed with a Cox regression model,
      using statin treatment as a time-varying covariate. RESULTS: Among the 13,783
      patients, 5417 (39%) received statin treatment. Statin-treated patients were
      younger with fewer comorbid conditions. After propensity adjustment, the baseline
      characteristics of the statin-treated and untreated patients were similar. During
      an average follow-up of 4.8 years, 1979 (14%) patients developed AF. In the
      overall study population there was no difference in AF incidence with statin
      treatment (hazard ratio 1.0, 95% CI 0.88-1.14, P = .9). However, AF was less
      common among statin-treated patients with CHF (hazard ratio 0.57, 95% CI 0.33
      1.00, P = .04). CONCLUSIONS: We did not find any effect of statin treatment on AF
      incidence in patients with CHD; however, AF was reduced in a subset of patients
      with CHF.

PMID- 18035088
TI  - The effect of leisure-time physical activity on the presence of metabolic
      syndrome in patients with manifest arterial disease. The SMART study.
AB  - BACKGROUND: Physical activity can influence insulin sensitivity and metabolic
      syndrome (MetS) independent of weight loss. Therefore, we investigated the
      independent effect of leisure-time physical activity on the prevalence of MetS
      and insulin resistance in patients with manifest arterial disease and the role of
      body fat and fat distribution on this relationship. METHODS: Data were collected
      from the Second Manifestations of ARTerial disease study, an ongoing prospective
      cohort study of patients with manifest vascular disease or vascular risk factors
      at the University Medical Center Utrecht. Data of 1097 patients, mean age 58.3 +/
      10.4 years, with clinically manifest arterial disease were used. Information on
      leisure-time physical activity (sporting or other physical exercise) during the
      past year was collected using a questionnaire. Patients were classified according
      to the time spent doing leisure-time physical activities: 0 metabolic equivalent
      (MET)/h per week (64%), 1.0 to 14.9 MET/h per week (16%), and >15.0 MET/h per
      week (20%). RESULTS: The prevalence of MetS was markedly lower (20%) in
      physically active patients (>15 MET/h per week active) than in physically
      inactive patients (36%; odds ratio [OR] 0.50, 95% confidence interval [CI] 0.33
      0.75) after adjustment for age, sex, body mass index, and smoking. After
      adjustment for age, sex, waist circumference, and smoking, the OR of having MetS
      remained essentially the same (OR 0.59, 95% CI 0.38-0.90). Patients who were
      active (>15 MET/h per week active) had a considerable lower risk of insulin
      resistance (homeostasis model assessment determined insulin resistance >2.38)
      than inactive patients (OR 0.40, 95% CI 0.25-0.64) after adjustment for age, sex,
      body mass index, and smoking. CONCLUSIONS: Patients with manifest arterial
      disease who are physically active are less likely to have MetS and insulin
      resistance than physically inactive patients, although body weight is comparable
      between the groups.

PMID- 18035089
TI  - Congestive heart failure disease management in Medicare-managed care.
AB  - BACKGROUND: In 2001, the Center for Medicare and Medicaid Services began 2
      initiatives that encouraged Medicare-managed care plans to introduce congestive
      heart failure (CHF) disease management programs. Our study was designed to
      describe the use, structure, and content of these programs. METHODS: In 2003 to
      2004, we invited the representatives of Medicare-managed care plans with > or =
      750 enrollees to participate in a survey by mail or telephone. RESULTS:
      Representatives of 120 plans, 84 (70%) responded. Of the plans, 92% had CHF
      programs, 45% of which were instituted in 2001 or later, and 42% of which were
      handled externally by commercial vendors. Vendor use was more common in large
      programs (> 30,000 Medicare enrollees) than in small programs (< 15,000 Medicare
      enrollees) (57% vs 24%, P = .05), in national than local programs (50% vs 21%, P
      = .03), and in for-profit than not-for-profit programs (45% vs 21%, P = .03).
      Although 87% of CHF programs focused on improving patient self-management, a
      smaller fraction engaged practicing physicians (eg, 23% provided feedback to
      physicians concerning whether care was consistent with CHF guidelines).
      CONCLUSIONS: In Medicare-managed care plans, there is widespread use of CHF
      disease management. However, the programs used primarily focus on patient self
      management and not on engaging physicians on medication management and compliance
      with guidelines. Our findings raise the concern that these programs will not be
      able to achieve the quality improvement and cost savings previously demonstrated
      in clinical trials of CHF disease management.

PMID- 18035090
TI  - Myocardial contractile reserve predicts improvement in left ventricular function
      after cardiac resynchronization therapy.
AB  - BACKGROUND: Myocardial contractile reserve has been shown to provide important
      prognostic information in patients with heart failure. We hypothesized that
      myocardial contractile reserve would predict left ventricular (LV) reverse
      remodeling after cardiac resynchronization therapy (CRT). METHODS: Thirty-one
      consecutive patients with heart failure (LV ejection fraction [LVEF] 26% +/- 7%,
      35% nonischemic cardiomyopathy) underwent echocardiography during low-dose
      dobutamine infusion before CRT implantation to assess global contractile reserve
      (improvement in LVEF) and local contractile reserve in the region of the LV
      pacing lead (assessed by radial strain using speckle tracking analysis).
      Responders were defined by a decrease in LV end-systolic volume > or = 15% after
      6 months of CRT. RESULTS: During low-dose dobutamine infusion, responders showed
      a greater increase in LVEF compared with nonresponders (delta 13% +/- 8% vs 3% +/
      4%, P < .001). Furthermore, contractile reserve was directly related to
      improvement in LVEF after 6 months of CRT (r = 0.80, P < .001). Moreover, a
      cutoff value of > 7.5% increase in dobutamine-induced LVEF exhibited a
      sensitivity of 76% and a specificity of 86% to predict response after 6 months of
      CRT (area under the curve 0.87). Lastly, contractile reserve in the region in the
      LV pacing lead was present only in responders (delta strain during low-dose
      dobutamine 6% +/- 5% in responders vs -1% +/- 4% in nonresponders, P = .002).
      CONCLUSIONS: The current study demonstrates that myocardial contractile reserve
      (> 7.5% increase in LVEF during low-dose dobutamine infusion) predicts LV reverse
      remodeling after CRT.

PMID- 18035091
TI  - The clinical features of transient left ventricular nonapical ballooning
      syndrome: comparison with apical ballooning syndrome.
AB  - BACKGROUND: Recently, several cases of atypical left ventricular (LV) ballooning
      syndrome without involvement of the LV apex have been reported. However, there
      has been no assessment of the clinical features of this novel presentation or
      comparison with the typical transient LV apical ballooning syndrome. METHODS: We
      evaluated 47 patients diagnosed with transient LV ballooning syndrome. The
      diagnostic criteria were (1) transient akinesia/dyskinesia beyond a single major
      coronary artery vascular distribution, (2) absence of significant coronary artery
      disease on coronary angiograms, and (3) new electrocardiographic changes.
      RESULTS: Thirty-one patients showed classic LV apical ballooning, and 16 showed
      atypical LV ballooning without involvement of the LV apex (nonapical ballooning).
      Clinical presentations and inhospital courses of illness were mostly similar
      among patients with nonapical ballooning (group NA) and patients with apical
      ballooning (group A). However, on admission, there were fewer patients with
      cardiogenic shock or pulmonary edema in group NA than in group A (19% vs 48%, P =
      .048). Group NA patients were relatively younger than group A patients (median
      ages 58 vs 70 years, P = .02), and fewer patients had coronary risk factors in
      group NA than in group A (38% vs 77%, P = .01). On electrocardiogram, T-wave
      inversion was noted less frequently in the NA group than in the A group (69% vs
      97%, P = .01). CONCLUSIONS: Transient LV nonapical ballooning syndrome and
      classic LV apical ballooning syndrome may be different manifestations of a single
      syndrome. They appear to have differences in the severity of heart failure, in
      patient characteristics, and in electrocardiographic change.

PMID- 18035092
TI  - The impact of patient-specific quality-of-care report cards on guideline
      adherence in heart failure.
AB  - BACKGROUND: It is unknown if physician education through heart failure (HF)
      patient-specific quality-of-care report cards (HFRC) impacts outpatient HF
      guideline adherence. METHODS: A prospective pre-post design study was performed
      to test the hypothesis that a one-time, patient-specific HFRC delivered to
      physicians after HF patient (ejection fraction < or = 40%) discharge would lead
      to improved HF guideline adherence compared with control practitioners. Patients
      were contacted at 1, 3, and 6 months after discharge to assess medication usage
      and intolerances. Six month quality score (QS) was the primary end point,
      calculated as the sum of adherence to 4 medication performance measures
      (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta
      blockers, aldosterone inhibitors, and warfarin for atrial fibrillation). RESULTS:
      The mean QS at discharge was 3.10 +/- 0.78 in controls (n = 189) and 3.25 +/-
      0.79 in the HFRC group (n = 76, P = .11). Controlling for discharge QS, the HFRC
      resulted in a significantly improved QS at 3 months (beta = .11, P = .023) but
      not at the 6-month primary end point (beta = .084, P = .14). Controlling for
      baseline medication use, patients of practitioners receiving the HFRC were 32.5
      (P = .019) and 8.5 (P = .030) times more likely to receive, or have a documented
      contraindication to, an angiotensin-converting enzyme inhibitor/angiotensin
      receptor blocker at 3 and 6 months, respectively. There were no significant
      differences in indicated beta-blocker, aldosterone inhibitor, or warfarin
      prescriptions at any follow-up. CONCLUSIONS: Although one-time patient-specific
      report cards result in short-term statistically significant improvements in
      outpatient evidence-based HF care, the gain does not translate into sustained
      improvements in quality of care.

PMID- 18035093
TI  - In patients with ST-segment elevation myocardial infarction with cardiogenic
      shock treated with percutaneous coronary intervention, admission glucose level is
      a strong independent predictor for 1-year mortality in patients without a prior
      diagnosis of diabetes.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) reduces mortality in
      patients with ST-segment elevation myocardial infarction (STEMI) complicated by
      cardiogenic shock (CS). Despite PCI, mortality in CS is still approximately 50%.
      Admission glucose concentration is an independent predictor of mortality in
      patients with STEMI and is associated with the occurrence of CS. Whether
      admission glucose is also a predictor of mortality in CS patients treated with
      primary PCI is unexplored. We therefore assessed the relation between admission
      glucose concentration and 1-year mortality in patients with STEMI with CS without
      a prior diagnosis of diabetes on admission and treated with PCI. METHODS: We
      investigated a cohort of 208 consecutive patients with STEMI without a prior
      diagnosis of diabetes with CS on admission. Patients were classified according to
      glucose levels at admission: <7.8 mmol/L (group 1, n = 57), 7.8 to 11 mmol/L
      (group 2, n = 71), and >11.0 mmol/L (group 3, n = 80). RESULTS: The overall 1
      year mortality was 38%. One-year mortality was 21%, 27%, and 60% in groups I, II,
      and III, respectively (P < .001). In a multivariate logistic regression analysis,
      the odds for mortality increased by 16% for every 1 mmol/L increase in plasma
      glucose concentration (OR 1.155, 95% CI 1.070-1.247), after adjustment for left
      ventricular ejection fraction <40%, age older than 75 years, male sex, and
      thrombolysis in myocardial infarction 3 flow after PCI. CONCLUSIONS: In patients
      with STEMI with CS and without a prior diagnosis of diabetes undergoing primary
      PCI, admission glucose concentration is a very strong independent predictor for 1
      year mortality. Further studies are warranted to determine whether concomitant
      glycometabolic regulation in patients with STEMI treated with PCI, particularly
      those with CS, will improve clinical outcome.

PMID- 18035094
TI  - Comprehensive evaluation of noncalcified coronary plaque characteristics detected
      using 64-slice computed tomography in patients with proven or suspected coronary
      artery disease.
AB  - BACKGROUND: Multislice computed tomography has recently been shown to have the
      potential to characterize noncalcified coronary atherosclerotic lesions (NCALs).
      We evaluated the relationship among computed tomography (CT) density, arterial
      remodeling, and the adherent calcium morphology of NCALs detected using 64-slice
      CT. METHODS: We studied 138 patients with proven or suspected coronary artery
      disease who underwent contrast-enhanced 64-slice CT examination. For each NCAL
      detected within the vessel wall, we determined the minimum CT density, remodeling
      index (RI = lesion/reference vessel area), and the presence or absence of
      coronary calcium in or adjacent to each NCAL and its morphology. Intravascular
      ultrasound (IVUS) was additionally performed in a subset of 21 patients. RESULTS:
      A total of 202 NCALs were detected in 97 patients. The mean CT density of 98
      lesions with positive remodeling (PR) (RI >1.05) was significantly lower than
      that of 104 lesions without PR (25 +/- 23 vs 56 +/- 28 Hounsfield units, P <
      .001); and spotty calcium was more frequently observed with the PR lesions than
      non-PR lesions (59% vs 22%, P < .001). The mean CT density of the PR lesions with
      spotty calcium (n = 58) was substantially lower than that of the non-PR lesions
      without adherent calcium (n = 45) (20 +/- 20 vs 67 +/- 24 Hounsfield units, P <
      .001). Evaluation of the components, RI, and adherent calcium morphology of 38
      NCALs by 64-slice CT was in close agreement with the IVUS findings. CONCLUSIONS:
      Lower CT density, PR, and adherent spotty calcium, which may indicate plaque
      vulnerability, are intimately co-related in NCALs detected using 64-slice CT;
      these findings are consistent with those of IVUS.

PMID- 18035095
TI  - Left atrial appendage filling defects identified by multidetector computed
      tomography in patients undergoing radiofrequency pulmonary vein antral isolation:
      a comparison with transesophageal echocardiography.
AB  - BACKGROUND: Patients referred for radiofrequency pulmonary vein antral isolation
      undergo contrast-enhanced multidetector computed tomography (MDCT) to assess
      pulmonary vein and left atrial anatomy as well as transesophageal
      echocardiography (TEE) to detect intraatrial thrombus. We sought to determine the
      accuracy of MDCT to qualitatively and quantitatively detect severe spontaneous
      echo contrast (SEC) or thrombus by TEE in the left atrial appendage (LAA).
      METHODS: Two hundred twenty-three consecutive MDCT and TEE studies performed
      within 7 days of each other were retrospectively identified. The LAA was
      evaluated by MDCT for filling defects and by TEE for thrombus or SEC. Severe SEC
      or thrombus on TEE was considered positive. In patients with preserved ejection
      fraction, the Hounsfield unit (HU) density of a 1-cm2 region of interest was
      measured in the LAA and ascending aorta (AA) of the same slice to calculate an
      LAA/AA HU ratio. RESULTS: Visually identified filling defects in LAA by MDCT
      correspond to severe SEC and thrombus with a sensitivity, specificity, positive
      predictive value, and negative predictive value of 93%, 85%, 31%, and 99%,
      respectively. Multidetector CT missed severe SEC detected by TEE in one
      examination; all thrombi, however, were correctly identified. There is a
      significant inverse association between mean LAA/AA HU ratios with increasing
      grades of SEC or thrombus (P < .001). Using an LAA/AA HU ratio cutoff of 0.25,
      the positive predictive value and specificity increased to 75% and 96%,
      respectively, while preserving a high negative predictive value (96%).
      CONCLUSIONS: Multidetector CT can qualitatively and quantitatively identify and
      distinguish severe LAA SEC/thrombus from lesser grades of SEC.

PMID- 18035096
TI  - A framework for quality improvement: an analysis of factors responsible for
      improvement at hospitals participating in the Can Rapid Risk Stratification of
      Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of
      the ACC/AHA Guidelines (CRUSADE) quality improvement initiative.
AB  - BACKGROUND: Hospitals are under increasing pressure to improve their quality of
      care. However, a key question remains: how can hospitals best design and
      implement successful quality improvement (QI) programs? Hospitals currently
      employ a variety of QI initiatives but have little empirical evidence on which to
      base their quality efforts. METHODS: We designed and applied a hospital cross
      sectional survey to 212 hospitals participating in CRUSADE (Can Rapid Risk
      Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early
      Implementation of the American College of Cardiology/American Heart Association
      Guidelines), a voluntary QI initiative of patients with non-ST-segment elevation
      acute coronary syndromes (NSTE ACS). We factor analysis and an ordinary least
      squares regression model to determine the key hospital factors most associated
      with unexpected improvements in institutional QI in the treatment of NSTE ACS.
      RESULTS: From 2002 to 2004, the following factors had a significant association
      with unexpected increases in the 2004 QI in NSTE ACS treatment: the use of
      CRUSADE QI tools, clinical commitment to quality by a cardiology coadvocate,
      institutional financial commitment to quality, and barriers to QI related to
      resource availability and cultural resistance to change (all P < .10). Of these
      factors, optimal use of CRUSADE QI tools was associated with the highest absolute
      improvement in process adherence score relative to other factors. CONCLUSIONS: We
      identified several institutional factors associated with improved quality of care
      in the treatment of high-risk NSTE ACS. We hope that this evidence-based
      framework will help guide the development and implementation of future QI
      programs in order to improve the institutional quality of care for NSTE ACS.

PMID- 18035097
TI  - Cost-effectiveness of sirolimus-eluting stents compared with vascular
      brachytherapy for the treatment of in-stent restenosis.
AB  - BACKGROUND: Sirolimus-eluting stents (SESs) were recently shown to be superior to
      vascular brachytherapy for the treatment of restenosis within a bare metal stent.
      No economic comparison of these alternative strategies has yet been reported.
      METHODS: We conducted a prospective health economic study involving all patients
      randomized to SES (n = 259) or brachytherapy (n = 125) in the SISR trial.
      Procedural, hospital, and outpatient costs, as well as physician fees, were
      estimated through 12 months based on measured resource use and itemized hospital
      bills. Cost-effectiveness was assessed in terms of the cost per repeat
      revascularization avoided, cost per major adverse cardiac event avoided, and cost
      per event-free patient. RESULTS: Although initial device costs were approximately
      $1100/patient higher in the SES group, this was offset by higher physician fees
      associated with brachytherapy, such that initial hospitalization costs were
      similar for the 2 groups. Because SES significantly reduced repeat
      revascularization procedures and major adverse cardiac event compared with
      brachytherapy during follow-up, cumulative 12-month costs were significantly
      lower in the SES group ($16,482 vs $19,435, mean difference -$2953, 95% CI -$5470
      to -$792). Sirolimus-eluting stenting was thus both more effective and less
      expensive than brachytherapy, as confirmed in >98% of bootstrap replications for
      each of the cost-effectiveness outcomes. CONCLUSIONS: Compared with vascular
      brachytherapy, SES is an economically dominant strategy for the treatment of in
      stent restenosis.

PMID- 18035098
TI  - Oral testosterone supplementation and chronic low-grade inflammation in elderly
      men: a 26-week randomized, placebo-controlled trial.
AB  - BACKGROUND: To determine the effect of oral testosterone supplementation on
      systemic low-grade inflammation measured by high-sensitive C-reactive protein (hs
      CRP) in aging men with low testosterone levels. METHODS: Two hundred thirty-seven
      men aged 60 to 80 years with a testosterone level of <13.7 nmol/L (below the 50th
      percentile of the population distribution) were recruited into a double-blind
      randomized placebo-controlled trial. Participants were randomized to either 4
      capsules of 40 mg testosterone undecanoate (Andriol Testocaps, NV Organon, Oss,
      The Netherlands) or placebo daily for 26 weeks. Serum levels of hs-CRP were
      measured at baseline and at 26 weeks using a near-infrared particle immunoassay
      of the Synchron LX System (Beckman Coulter, Fullteron, CA). RESULTS: The median
      baseline hs-CRP level was 1.95 mg/L (0.30-6.43) in the testosterone group
      compared with 1.90 mg/L (0.40-5.91) in the placebo group. After 26 weeks of
      testosterone supplementation therapy, the 2 intervention groups were not
      statistically significantly different (median hs-CRP 2.20 vs 2.00 mg/L,
      interquartile range 0.40-6.54 vs 0.50-5.70, P = .36). In subgroup analysis,
      neither baseline testosterone level, nor age, nor baseline CRP-level modified the
      effect of testosterone supplementation on CRP levels. CONCLUSION: Oral
      testosterone undecanoate supplementation, in dosage of 160 mg daily for 26 weeks,
      does not increase hs-CRP levels in elderly men.

PMID- 18035099
TI  - Epidemiology of pure valvular regurgitation in the large middle-aged African
      American cohort of the Atherosclerosis Risk in Communities study.
AB  - BACKGROUND: There are limited data on the prevalence and the clinical and
      echocardiographic correlates of pure valvular regurgitation in African Americans
      despite the higher rates of cardiovascular disease in this group. PURPOSE: The
      Jackson, Mississippi, site of the Atherosclerosis Risk in Communities study
      provides a unique opportunity to study mitral regurgitation (MR), tricuspid
      regurgitation (TR), and aortic regurgitation (AR) in this population. METHODS:
      There were 2285 participants who were available for analysis. The prevalence
      rates of MR, TR, and AR by severity were calculated for participants aged 50 to
      59, 60 to 69, and > or = 70 years. Multivariable regression analyses were
      conducted to determine clinical and echo variables associated with the presence
      of MR, TR, and AR. RESULTS: Mild or greater MR and TR were present in 14.7% and
      17.2% of participants, respectively. Aortic regurgitation was present in 15.6% of
      participants. In the multivariable regression model, MR was independently
      associated with age, sex, lower body mass index (BMI), systolic blood pressure,
      left atrial size, left ventricular (LV) diastolic diameter, and low LV ejection
      fraction. Tricuspid regurgitation was independently associated with age, sex,
      lower BMI, high-density lipid, left atrial size, and lower relative wall
      thickness. Aortic regurgitation was independently associated with age, sex, lower
      BMI, systolic blood pressure, LV diastolic diameter, LV hypertrophy, and low LV
      ejection fraction. CONCLUSION: In this middle-aged African Americans cohort, the
      prevalence of mild to greater MR and TR was similar to that seen in other
      cohorts; however, AR was more prevalent. Several cardiovascular risk factors and
      echo parameters were identified as independent correlates of valvular
      regurgitation.

PMID- 18035100
TI  - Factors associated with development of atrial septal restriction in patients with
      tricuspid atresia involving the right-sided atrioventricular valve.
AB  - BACKGROUND: Clinical practice is discrepant regarding routine enlargement of the
      interatrial communication (IAC) in patients with right-sided atrioventricular
      valve atresia. We determined the percentage and risk factors of those who develop
      a restrictive IAC. METHODS: Medical records were reviewed for patients treated
      from 1985 to 2006, including those admitted in the first 6 weeks of life (group
      A), and those referred at a later age (group B), some of whom had routine atrial
      septal procedures. In group A, we analyzed the initial postnatal echocardiogram.
      RESULTS: Group A consisted of 79 patients, 16 of whom had an atrial septectomy as
      part of the initial surgical procedure. Of the remaining 63 patients, 9 (14%)
      developed atrial septal restriction. In group A, an atrial septal aneurysm (ASA)
      (OR 16, P = .006) and IAC diameter < 5 mm (OR 13, P = .009) were associated with
      atrial septal restriction. Atrial septal restriction occurred in 80% of patients
      with both features, 20% with IAC > or = 5 mm and ASA, 18% with IAC < 5 mm and no
      ASA, and 2% with neither feature. Group B consisted of 95 patients, 27 of whom
      had an atrial septal procedure. Of the remaining 68 patients, 11 (16%) developed
      atrial septal restriction. CONCLUSION: Routine enlargement of the IAC is not
      necessary in patients with right-sided atrioventricular valve atresia. Patients
      with ASA or IAC < 5 mm are at increased risk for development of atrial septal
      restriction.

PMID- 18035122
TI  - Hypertension/pre-hypertension in a pediatric sub-specialty clinic.

PMID- 18035123
TI  - Too many zeros in metoprolol.

PMID- 18035124
TI  - The egg or the chicken? Further data on whether good compliance to multi
      injection insulin therapy should be a criterion for insulin pump therapy, or does
      insulin pump therapy improve compliance?

PMID- 18035125
TI  - Pre-hypertension and hypertension among adolescents of Switzerland.

PMID- 18035126
TI  - The new generation of pediatric faculty.

PMID- 18035127
TI  - Is lack of bladder inhibition during sleep a mechanism of nocturnal enuresis?

PMID- 18035128
TI  - Gastroesophageal reflux in preterm infants: is positioning the answer?

PMID- 18035129
TI  - Staphylococcus aureus: a moving target.

PMID- 18035130
TI  - Prospects for development and potential impact of a vaccine against congenital
      cytomegalovirus (CMV) infection.

PMID- 18035131
TI  - Effect of 1-desamino-8-D-arginine vasopressin on prepulse inhibition of startle
      supports a central etiology of primary monosymptomatic enuresis.
AB  - OBJECTIVE: To test the hypothesis that 1-desamino-8-D-arginine vasopressin
      (dDAVP) has an effect on prepulse inhibition (PPI) of startle in patients with
      primary monosymptomatic enuresis (PME), thus indicating a central effect. STUDY
      DESIGN: Patients with PME (n = 21, age 6 to 12 years) were enrolled in a
      prospective, randomized, double-blinded, cross-over study. Startle reflexes and
      PPI were measured under dDAVP treatment versus placebo. RESULTS: The data show
      that dDAVP has a significant effect on PPI, raising it from 38.88% under placebo
      to the age-related normal level of 62.6% with dDAVP treatment (P = .0127).
      CONCLUSIONS: Our findings revive the concept of a central pathophysiology of PME
      and offer a different explanation for the effects of dDAVP, which not only acts
      on the kidney, but also is (as is AVP) a central neurotransmitter with a signal
      cascade on relevant reflex mechanisms.

PMID- 18035133
TI  - Urine output rate and maximum volume voided in school-age children with and
      without nocturnal enuresis.
AB  - OBJECTIVE: To compare urine volumes voided and output rates in prepubertal
      children with and without monosymptomatic nocturnal enuresis (MNE), to
      investigate the balance between nocturnal urine output and functional bladder
      capacity. STUDY DESIGN: In 76 prepubertal children with MNE, all voidings were
      collected over 48 hours: bedwetting volume (BWV), early-morning voiding after a
      dry night (EMV), and other voided volumes (VV). Output rates were calculated
      based on volumes voided and time intervals. Data collected in 50 typical
      prepubertal children were used for comparison. In both populations, holding
      exercise volumes (HEV) were also collected, to approximate maximum volume voided
      (MVV). RESULTS: Of the 15% total bedwetting events recorded with output rates
      more than 2 standard deviations above the normal population average, only half
      met the International Children's Continence Society criteria for "nocturnal
      polyuria." The circadian rhythm of urine output is the same in both populations;
      during inactivity, low rates and long filling times result in large EMV. BWVs are
      also produced with low rates, but have shorter filling times. MVV is small for
      age in MNE, but HEV for age is the same in both populations. Treating MNE with
      holding exercises needs to be studied prospectively. CONCLUSIONS: The cause of
      bedwetting might be aborted bladder filling in the circadian inactivity phase
      rather than nocturnal polyuria.

PMID- 18035134
TI  - Normal dimercaptosuccinic acid scintigraphy makes voiding cystourethrography
      unnecessary after urinary tract infection.
AB  - OBJECTIVE: To test the hypothesis that infants with dilating vesicoureteral
      reflux (VUR) have abnormal acute dimercaptosuccinic acid (DMSA) scintigraphy
      results, as was suggested by an earlier retrospective study. STUDY DESIGN: We
      conducted a prospective study of infants <1 year old with first diagnosed
      symptomatic urinary tract infection at the Children's Hospital of Goteborg,
      Sweden. Two hundred ninety consecutive children (161 boys and 129 girls) with
      complete records were examined. Renal ultrasound scanning and DMSA scintigraphy
      were performed within a few days from diagnosis, and VCU was performed within 2
      months. RESULTS: VUR was found in 52 children, of which 27 had dilating VUR
      (grade III-V). DMSA scintigraphy results were abnormal in 149 infants (51%), 105
      of 238 (44%) without VUR, 18 of 25 (72%) with VUR grade I to II, and 26 of 27
      (96%) with VUR grade III to V (P <.001). CONCLUSION: DMSA scintigraphy results
      were abnormal in all 27 infants with dilating VUR except 1. This single false
      negative finding should be compared with 140 unnecessary VCU investigations. This
      supports our hypothesis that DMSA scintigraphy results are abnormal when there is
      dilating VUR. Thus, a normal DMSA scan makes VCU unnecessary in the primary
      examination of infants with UTI.

PMID- 18035135
TI  - Effect of body position changes on postprandial gastroesophageal reflux and
      gastric emptying in the healthy premature neonate.
AB  - OBJECTIVE: To identify a body-positioning regimen that promotes gastric emptying
      (GE) and reduces gastroesophageal reflux (GER) by changing body position 1 hour
      after feeding. STUDY DESIGN: Ten healthy preterm infants (7 male; mean
      postmenstrual age, 36 weeks [range, 33 to 38 weeks]) were monitored with combined
      esophageal impedance-manometry. Infants were positioned in the left lateral
      position (LLP) or right lateral position (RLP) and then gavage-fed. After 1 hour,
      the position was changed to the opposite side. Subsequently, all infants were
      restudied with the order of positioning reversed. RESULTS: There was more liquid
      GER in the RLP than in the LLP (median, 9.5 [range, 6.0 to 22.0] vs 2.0 [range,
      0.0 to 5.0] episodes/hour; P = .002). In the RLP-first protocol, the number of
      liquid GER episodes per hour decreased significantly after position change (first
      postprandial hour [RLP], 5.5 [2.0 to 13.0] vs second postprandial hour [LLP], 0.0
      [0.0 to 1.0]; P = .002). GE was faster in the RLP-first protocol than in the LLP
      first protocol (37.0 +/- 21.1 vs 61.2 +/- 24.8 minutes; P = .006). CONCLUSIONS: A
      strategy of right lateral positioning for the first postprandial hour with a
      position change to the left thereafter promotes GE and reduces liquid GER in the
      late postprandial period and may prove to be a simple therapeutic approach for
      infants with GER disease.

PMID- 18035136
TI  - The effect of body positioning on gastroesophageal reflux in premature infants:
      evaluation by combined impedance and pH monitoring.
AB  - OBJECTIVE: To evaluate the pattern of acid and nonacid gastroesophageal reflux
      (GER) in different body positions in preterm infants with reflux symptoms by a
      combined multichannel intraluminal impedance (MII)-pH monitoring, which
      identifies both acid and nonacid GER. STUDY DESIGN: Premature infants with
      frequent regurgitation and postprandial desaturation (n = 22) underwent a 24-hour
      recording of MII-pH. In a within-subjects design, reflux indexes were analyzed
      with the infants in 4 different positions: supine (S), prone (P), on the right
      side (RS), and on the left side (LS). RESULTS: All infants were analyzed for 20
      hours. The mean number of recorded GER episodes was 109.7. The mean esophageal
      exposure to acid and nonacid GER was lower in positions P (4.4% and 0.3%,
      respectively) and LS (7.5% and 0.7%, respectively) than in positions RS (21.4%
      and 1.2%, respectively) and S (17.6% and 1.3%, respectively). The number of
      postprandial nonacid GER episodes decreased but the number of acid GER episodes
      increased over time. The LS position showed the lowest esophageal acid exposure
      (0.8%) in the early postprandial period, and the P position showed the lowest
      esophageal acid exposure (5.1%) in the late postprandial period. CONCLUSION:
      Placing premature infants in the prone or left lateral position in the
      postprandial period is a simple intervention to limit GER.

PMID- 18035137
TI  - Pharyngeal swallowing: defining pharyngeal and upper esophageal sphincter
      relationships in human neonates.
AB  - OBJECTIVE: To test the hypothesis that the sensorimotor characteristics of the
      reflexes evoked on stimulation with air and water infusions differ by studying
      the effect of pharyngeal stimulation on pharyngeal-upper esophageal sphincter
      (UES) interactions in healthy neonates. STUDY DESIGN: Pharyngo-UES-esophageal
      manometry was recorded in 10 neonates at 39 +/- 4 weeks postmenstrual age.
      Pharyngeal infusions (n = 155) of air (0.1 to 2.0 mL) and sterile water (0.1 to
      0.5 mL) were given. Two types of reflexes were recognized: pharyngeal reflexive
      swallowing (PRS) and pharyngo-UES-contractile reflex (PUCR). Frequency
      occurrence, distribution of reflexes, threshold volume, response time, and
      stimulus-response relationship were evaluated. RESULTS: The reflex response rates
      were 30% for air and 76% for water (P < .001). PRS was more frequent than PUCR
      with air and water (P < .05), even though the stimulation thresholds and response
      latencies were similar. Graded volumes of water but not air resulted in an
      increased frequency of PRS (P < .01). CONCLUSIONS: PRS is more frequent than
      PUCR, and the 2 reflexes have distinctive characteristics in air and water
      stimuli. Both PRS and PUCR have implications for the evaluation of swallowing in
      infants.

PMID- 18035139
TI  - Racial differences in the use of respiratory medications in premature infants
      after discharge from the neonatal intensive care unit.
AB  - OBJECTIVE: To determine the effect of race and ethnicity on the use of oral beta
      agonists, inhaled beta-agonists, and inhaled corticosteroids to treat respiratory
      symptoms in former premature infants after controlling for medical conditions,
      socioeconomic status, and site of outpatient care. STUDY DESIGN: Using a
      population cohort of infants born at a gestational age < or = 34 weeks at 5
      Northern California Kaiser Permanente hospitals between 1998 and 2001 (n = 1436),
      we constructed multivariable models to determine predictive factors for the
      receipt of respiratory medications during the first year after discharge.
      RESULTS: After controlling for confounding factors, black infants were more
      likely to receive oral beta-agonists compared with white infants (OR 4.30, 95% CI
      2.33-7.94), and Hispanic infants were less likely to receive inhaled beta
      agonists (OR 0.62, 95% CI 0.39-0.99) or inhaled corticosteroids (OR 0.28, 95% CI
      0.12-0.67). These findings were not explained by more outpatient visits for
      respiratory symptoms in black or Hispanic infants, because the observed racial
      differences persisted when children of similar respiratory symptoms were
      examined. CONCLUSIONS: Even in a high-risk population of insured infants,
      substantial racial differences persist in the use of respiratory medications that
      could not be explained by differences in respiratory symptoms.

PMID- 18035140
TI  - Early elective insulin therapy can reduce hyperglycemia and increase insulin-like
      growth factor-I levels in very low birth weight infants.
AB  - OBJECTIVE: To investigate the use of insulin throughout the first week of life in
      very low birth weight (VLBW) infants (birth weight <1.5 kg) to improve glucose
      control and increase insulin-like growth factor-I (IGF-I) levels. IGF-I is the
      dominant hormone involved in fetal growth, and low levels have been implicated in
      neonatal morbidities, such as retinopathy of prematurity. STUDY DESIGN: In this
      pilot randomized controlled study (n = 16), the intervention group received
      insulin (0.025 U/kg/hr) on days 1 to 7, with 20% dextrose to maintain
      normoglycemia. Control infants received standard neonatal care. All infants
      received continuous glucose monitoring. RESULTS: The intervention and standard
      care groups had similar mean gestational age (+/- standard deviation), 26.2 (+/-
      2.5) vs 26.9 (+/- 2.7) weeks, and birth weight, 0.79 (+/- 0.26) vs 0.73 (+/-
      0.16) kg. The standard care infants were hyperglycemic (sensor glucose >10 mmol/L
      [180 mg/dL]) for 35.9% of the study period, compared with 7.6% for the insulin
      treated infants (P = .035). The duration of time with hypoglycemia (<2.6 mmol/L
      [47 mg/dL]) did not differ between the 2 groups (P = .746). The insulin-treated
      group had a 2.4-fold increase in mean IGF-I bioactivity (P = .005). CONCLUSIONS:
      Early insulin therapy improves blood glucose control and increases IGF-I
      bioactivity levels. This could result in less morbidity associated with
      hyperglycemia and reduced IGF-I levels.

PMID- 18035141
TI  - Maternal smoking and the vitamin D-parathyroid hormone system during the
      perinatal period.
AB  - OBJECTIVE: To evaluate the effect of smoking on the vitamin D-parathyroid hormone
      (PTH) system during the perinatal period. STUDY DESIGN: Sixty-one healthy women
      with singleton pregnancies and their newborns participated in a cohort study. We
      compared serum PTH and BsmI polymorphism of the vitamin D receptor gene, 25
      hydroxyvitamin D (25(OH)D), 1,25 dihydroxyvitamin D, calcium, phosphorus, and
      bone alkaline phosphatase (bALP) in a smoking group (n = 32) versus a non-smoking
      group (n = 29), controlling for lifestyle confounders. The mothers were examined
      at 30 to 32 weeks and 38 to 40 weeks of pregnancy, and the infants were examined
      at 2 to 3 days of postnatal life. RESULTS: Mothers who smoked and their newborns
      showed decreased serum PTH (30-32 weeks, 26.9 +/- 10.7 pg/mL versus 37.1+/-19.5
      pg/mL; 38-40 weeks, 32.2 +/- 13.5 pg/mL versus 46.2 +/- 21.9 pg/mL, P = .005;
      newborns, 43.4 +/- 21.8 versus 64.1 +/- 34.2 pg/mL, P = .02) and increased
      phosphorus. Newborns of mothers who smoked also had significantly lower
      anthropometric measurements and serum 25(OH)D (14.2 +/- 6.2 ng/mL versus 22.3 +/-
      11.3 ng/mL, P = .009). In addition, pregnant women who smoked had lower bALP (30
      32 weeks, 31 +/- 15 U/L versus 44+/-29 U/L; 38-40 weeks, 55 +/- 32 U/L versus 97
      +/- 62 U/L, P = .005). CONCLUSIONS: Smoking during pregnancy negatively
      influences calcium-regulating hormones, leading to relative hypoparathyroidism in
      both the mother and their newborns.

PMID- 18035142
TI  - Early hemodynamic consequences of patent ductus arteriosus in preterm infants
      with intrauterine growth restriction.
AB  - OBJECTIVE: To test the hypothesis that significant patent ductus arteriosus (PDA)
      may occur very early after birth in preterm infants with intrauterine growth
      restriction (IUGR), we compared the longitudinal changes in left-to-right
      shunting through DA between eutrophic and preterm infants with IUGR. STUDY
      DESIGN: The preterm infants -26 to 32 weeks gestational age (GA), admitted in our
      neonatal intensive care unit from February to May 2004 were included. They were
      separated into an "IUGR of placental origin" group and an "eutrophic" group.
      Significant PDA was assessed by Doppler echocardiography at 6, 24, and 48 hours
      of age. RESULTS: Thirty-one eutrophic (GA = 29 +/- 1.4 weeks; birth weight [BW] =
      1300 +/- 160 g) and 17 infants with IUGR (GA = 29.3 +/- 1.5 weeks; BW = 810 +/-
      140 g) were studied. Six hours after birth, the rate of significant PDA was
      higher in the IUGR than in the eutrophic group (10/17 [60%] vs 5/31 [15%]; P <
      .05). More DA became significant in infants with IUGR (11/17 [65%]) than in
      eutrophic infants (12/31 [40%]) (P < .05) within the 48 hours after birth.
      CONCLUSION: Markers of high pulmonary blood flow and systemic vascular steal
      occur more frequently and earlier after birth in IUGR of placental origin than in
      eutrophic preterm infants. The management of preterm infants with severe IUGR of
      placenta origin should include early echocardiographic monitoring to assess for
      markers of significant PDA.

PMID- 18035143
TI  - Risk factors for persistent ductus arteriosus patency during indomethacin
      treatment.
AB  - OBJECTIVE: To test the hypothesis that patent ductus arteriosus that fail to
      close with prostaglandin inhibition may be regulated by mechanisms that act
      independently of prostaglandin production. STUDY DESIGN: We examined a cohort of
      446 infants who were treated with indomethacin (within 15 hours of birth) to
      inhibit prostaglandin production. We used multiple logistic regression modeling
      to determine which perinatal/neonatal variables were most closely associated with
      the persistence of ductus patency in the presence of diminished prostaglandin
      production. RESULTS: We identified 4 variables (immature gestational age, lack of
      exposure to antenatal betamethasone, severity of respiratory distress, and
      Caucasian race) that were significantly and independently associated with the
      degree of ductus patency. CONCLUSION: Gestational age, antenatal glucocorticoid
      exposure, respiratory distress, and race are independent risk factors that appear
      to affect ductus closure even when indomethacin has been used to inhibit
      prostaglandin production. Future studies of these risk factors may identify new
      potential targets for patent ductus arteriosus treatment.

PMID- 18035144
TI  - Self-perceived health, functioning and well-being of very low birth weight
      infants at age 20 years.
AB  - OBJECTIVE: To examine the self-perceived health of very low birth weight (VLBW;
      <1.5 kg) infants during young adulthood. STUDY DESIGN: The population included
      241 VLBW and 232 normal birth weight (NBW) controls who completed the Child
      Health and Illness Profile: Adolescent Edition (CHIP-AE) at 20 years of age. The
      CHIP-AE includes six domains: Satisfaction, Comfort, Resilience, Achievement,
      Risk Avoidance, and Disorders, and 13 profiles that characterize patterns of
      health. Results were compared between VLBW and NBW subjects adjusting for sex and
      sociodemographic status. RESULTS: VLBW subjects did not differ from NBW controls
      in the domains of Satisfaction or Comfort but reported less Resilience (effect
      size [ES] -0.19, P < .05), specifically in physical activity and family
      involvement. They reported better Achievement, specifically in work performance
      (ES 0.28, P < .05), more Risk Avoidance (ES 0.43, P < .001), and significantly
      more long-term medical, surgical, and psychosocial disorders. Similar proportions
      of VLBW and NBW subjects reported Excellent (15% vs 11%), Average (27% vs 34%),
      and Poor (12% vs 13%) profiles of health. CONCLUSIONS: VLBW subjects report
      similar health, well-being, and functioning compared with NBW controls and
      greater risk avoidance. However, we are concerned that their lesser resilience
      may prove detrimental to their future adult health.

PMID- 18035145
TI  - Children's dairy intake in the United States: too little, too fat?
AB  - OBJECTIVE: To compare reported dairy/calcium intake with intake recommendations
      and examination of food sources and fat levels of dairy intake in the National
      Health and Nutrition Examination Survey 1999-2002. STUDY DESIGN: Dietary,
      anthropometric, and sociodemographic data for 2- to 18-year-olds (n = 7716) were
      evaluated to compare intakes of dairy (MyPyramid) and calcium (Adequate Intake
      [AI]) recommendations. US Department of Agriculture food codes were used to
      identify mutually exclusive food groups of dairy-contributing foods, which were
      ranked in descending order proportional to total intake. Complex sample survey
      Student t tests were used to determine statistical significance among intakes in
      4 age groups and between reported and recommended intakes. RESULTS: Dairy
      consumption was not significantly different among age groups, but only 2- to 3
      year-olds met the MyPyramid recommendation. Calcium intake was significantly
      different among age groups, and 2- to 8-year-olds met the AI. Intake of flavored
      milk ranged from 9% to 18%. More than half of the milk consumed by 2- to 3-year
      olds was whole milk, and, with the exception of yogurt consumption in 2- to 3
      year-olds, children choose to consume more of the highest-fat varieties of
      cheese, yogurt, ice cream, and dairy-based toppings. CONCLUSIONS: Dairy and
      calcium intakes are inadequate in 4- to 18-year-olds. Most children consume the
      high-fat varieties of milk and dairy products. Focusing nutrition guidance
      efforts on increasing the intake of the low-fat dairy products, with special
      emphasis on increasing calcium intake in school-age children and adolescents
      through flavored low-fat milk products, may be beneficial.

PMID- 18035146
TI  - Fat cell size, insulin sensitivity, and inflammation in obese children.
AB  - OBJECTIVE: To assess the association between adiposity indexes (body mass index
      [BMI], fat mass, adipocyte size) and circulating inflammation markers with known
      metabolic relevance or insulin sensitivity in overweight/obese children. STUDY
      DESIGN: Twenty-eight children (males/females: 13/15) with different degrees of
      overweight (BMI z-score: 1.64-3.1; fat mass: 14.1-49.8 kg) were studied. BMI,
      body composition (dual-energy x-ray absorptiometry scanning), subcutaneous
      adipocyte diameter (needle biopsy of subcutaneous abdominal fat), blood tumor
      necrosis factor-alpha and interleukin-6 concentrations and insulin sensitivity
      (frequently sampled intravenous glucose tolerance test) were assessed. RESULTS:
      Adipocyte diameter, more than BMI and fat mass, was significantly associated with
      interleukin-6 (r = 0.62, P < .001) and tumor necrosis factor-alpha (r = 0.61, P <
      .001). Moreover adipocyte size was associated with insulin sensitivity (R2 =
      0.15, F = 4.69, P = .04) independently from fat mass. CONCLUSIONS: Adipocyte size
      is a factor linked to both inflammation and insulin resistance in
      overweight/obese children. This is similar to the findings in adults and lends
      support to the tenet that the earlier obesity ensues, the more severe the
      biologic consequences may be.

PMID- 18035147
TI  - Glucose tolerance, insulin secretion, and insulin sensitivity in children and
      adolescents with cystic fibrosis and no prior history of diabetes.
AB  - OBJECTIVE: To determine the prevalence of abnormalities of glucose metabolism in
      pediatric outpatients with cystic fibrosis (CF). STUDY DESIGN: Children and
      adolescents (n = 73, mean age 15.0 +/- 3.7 years) with CF not previously
      diagnosed with diabetes underwent 3-hour oral glucose tolerance testing. All
      subjects with CF were clinically stable and were not being treated for active
      infection. A reference group of young lean adults was used for comparison.
      Subjects were classified as having normal glucose tolerance (NGT) or abnormal
      glucose metabolism (AGM), including impaired glucose tolerance (IGT), impaired
      fasting glucose (IFG), or diabetes, by standard criteria. The insulinogenic index
      was calculated as a measure of beta-cell function, and insulin resistance was
      estimated with the homeostatic model assessment. RESULTS: The reference group was
      significantly older than the patients with CF, but in the control subjects, the
      AGM and NGT were comparable in body mass index z-scores (-0.8 +/- 1.3, -0.6 +/-
      1.1, -0.21 +/- 0.9 kg/m2). Thirty-eight percent of subjects with CF had AGM: 43%
      IGT, 29% IFG, 14% IGT/IFG, and 14% diabetes. In spite of distinct differences in
      glycemic response, the subjects with NGT and AGM had marked abnormalities of
      insulin secretion relative to the control subjects (Insulinogenic index 5.8 +/-
      1.0, 5.3 +/- 0.8, and 53.5 +/- 10.0 uU/mL/mmol/L, respectively; P < .0001).
      Insulin sensitivity did not differ among the 3 groups, although there was a trend
      toward greater insulin resistance in the subjects with AGM (homeostatic model
      assessment: CF-NGT 1.5 +/- 0.2, CF-AGM 1.9 +/- 0.3, REF 1.3 +/- 0.1, P = NS).
      CONCLUSION: Abnormalities in glucose metabolism are frequent in young patients
      with CF without a prior diagnosis of diabetes and are associated with marked
      defects in insulin secretion. Given the poor beta-cell function in patients with
      CF, even small reductions in insulin sensitivity may be an important determinant
      of AGM.

PMID- 18035148
TI  - Biliary atresia: the Canadian experience.
AB  - OBJECTIVE: To determine the outcomes of Canadian children with biliary atresia.
      STUDY DESIGN: Health records of infants born in Canada between January 1, 1985
      and December 31, 1995 (ERA I) and between January 1, 1996 and December 31, 2002
      (ERA II) who were diagnosed with biliary atresia at a university center were
      reviewed. RESULTS: 349 patients were identified. Median patient age at time of
      the Kasai operation was 55 days. Median age at last follow-up was 70 months. The
      4-year patient survival rate was 81% (ERA I = 74%; ERA II = 82%; P = not
      significant [NS]). Kaplan-Meier survival curves for patients undergoing the Kasai
      operation at age < or = 30, 31 to 90, and > 90 days showed 49%, 36%, and 23%,
      respectively, were alive with their native liver at 4 years (P < .0001). This
      difference continued through 10 years. The 2- and 4-year post-Kasai operation
      native liver survival rates were 47% and 35% for ERA I and 46% and 39% for ERA II
      (P = NS). A total of 210 patients (60%) underwent liver transplantation; the 4
      year transplantation survival rate was 82% (ERA I = 83%, ERA II = 82%; P = NS).
      CONCLUSIONS: This is the largest outcome series of North American children with
      biliary atresia at a time when liver transplantation was available. Results in
      each era were similar. Late referral remains problematic; policies to ensure
      timely diagnosis are required. Nevertheless, outcomes in Canada are comparable to
      those reported elsewhere.

PMID- 18035149
TI  - Constipation as cause of acute abdominal pain in children.
AB  - OBJECTIVE: To evaluate the causes of acute abdominal pain in a large academic
      pediatric primary care population. STUDY DESIGN: The complete charts of 962
      children, > or = 4 years old, who were seen for at least 1 health maintenance
      visit during a 6-month period, were reviewed retrospectively for complaints and
      cause of acute abdominal pain. RESULTS: We found that 9% of the 962 children had
      a visit for acute abdominal pain, with significantly more girls (12%) than boys
      (5%) having this complaint. Acute and chronic constipation were the most frequent
      causes of acute abdominal pain, occurring in 48% of subjects. A surgical cause
      was present in 2% of subjects. The cause for the acute abdominal pain remained
      unknown in 19% of subjects. We did not find significant differences in diagnoses
      in the primary care clinics versus emergency department. CONCLUSIONS: We found
      that constipation was the most common cause of acute abdominal pain in children.

PMID- 18035151
TI  - Prevalence of the MEFV gene mutations in childhood polyarteritis nodosa.
AB  - OBJECTIVES: To test the hypothesis that alterations in the Mediterranean fever
      (MEFV) gene are a susceptibility factor for the development of polyarteritis
      nodosa (PAN) we investigated the prevalence of MEFV mutations in patients with
      PAN without any symptoms of familial Mediterranean fever (FMF). STUDY DESIGN:
      Pediatric patients with PAN (n = 29) were enrolled in this study. Six predominant
      mutations (p.M694V, p.M680I, p.M694I, p.V726A, p.K695R, p.E148Q) in the MEFV gene
      were studied. RESULTS: Fifteen MEFV mutations were identified in 58 chromosomes.
      Eleven of the 29 patients (38%) were found to carry MEFV mutations. Three (10.3%)
      of them had homozygous p.M694V mutation, and one of the patients (3.4%) had
      compound heterozygous mutation (p.V726A/p.E148Q). CONCLUSIONS: Our study confirms
      that alterations in the MEFV gene are important susceptibility factors for the
      development of PAN. We believe that mutations in MEFV gene provide a basis for
      the development of PAN both by forming a proinflammatory state and by possibly
      giving exaggerated response to streptococcal infections.

PMID- 18035150
TI  - Size at birth, infant growth, and blood pressure at three years of age.
AB  - OBJECTIVES: Our aim was to determine the extent to which infant growth-in weight
      for-length-from birth to 6 months is associated with systolic blood pressure
      (SBP) at 3 years and to determine whether this association varies with birth
      size. STUDY DESIGN: In 530 children from the prospective cohort Project Viva, we
      measured birth length and 6-month weight and length with research standard
      instruments and SBP at age 3 years with a Dinamap automated recorder. We derived
      weight-for-length z-scores (WFL-z) and analyzed data with mixed effects
      regression models. RESULTS: The mean (SD) WFL-z was 0.47 (0.75) at birth and 0.70
      (0.96) at 6 months. Mean (SD) SBP at 3 years was 91.7 (9.4) mm Hg. After
      adjusting for confounding variables and birth WFL-z, child SBP was 1.0 mm Hg (95%
      CI 0.2, 1.8) higher for each z-score increment in 6-month WFL-z. The SBP of
      children in the lowest birth WFL-z quartile and the highest 6-month WFL-z
      quartile was 5.5 mm Hg (95% CI 2.6, 8.4) higher than that of children in the
      highest birth and lowest 6-month WFL-z quartiles. CONCLUSIONS: More rapid
      increase in weight-for-length, a measure of adiposity, in the first 6 months of
      life is associated with higher early childhood SBP, particularly in children who
      are thin at birth.

PMID- 18035153
TI  - Rheumatic chorea: relationship to systemic manifestations and response to
      corticosteroids.
AB  - OBJECTIVE: To describe Sydenham chorea among children in a cohort of patients
      with rheumatic fever (RF). STUDY DESIGN: An existing database was used to
      identify demographic characteristics, clinical manifestations, and therapy in
      persons with RF identified in Salt Lake City, Utah, from 1985 through January
      2002. RESULTS: Of 584 cases in the database, 537 (91%) were new-onset RF (median
      age of 10 years) and 177 (33%) had chorea. Patients with chorea were more often
      female (OR = 0.37, 95% CI = 0.25-0.55, P < .0001) and were less likely to have
      carditis or arthritis. Prednisone treatment may lead to a shortened course of
      chorea (4.0 weeks in prednisone-treated [n = 32] vs 9.0 weeks in untreated [n =
      14]; P < .0001). Among 33 patients seen at a median of 10.3 years (range 6.3-14.9
      years) after their initial bout of chorea, 20% reported residual tremor or mood
      swings. Ten of the 33 (30%) had one or more recurrences of chorea. CONCLUSIONS:
      Chorea affected one-third of the children with RF. Patients with chorea were less
      likely to have severe cardiac or rheumatologic complications of RF. Therapy with
      prednisone shortened the duration of rheumatic chorea; some reported recurrences
      of chorea and had minor neurologic sequelae.

PMID- 18035154
TI  - Multicenter prospective study of ulcerated hemangiomas.
AB  - OBJECTIVE: To identify clinical features of infants with ulcerated infantile
      hemangiomas. STUDY DESIGN: Cross-sectional analysis was conducted within a
      prospective cohort study of children with infantile hemangiomas. Children younger
      than 12 years of age were recruited. Demographic and prenatal/perinatal
      information was collected. Hemangioma size, location, subtype, course,
      complications, and treatments were recorded. RESULTS: One thousand ninety-six
      patients were enrolled, and 173 (15.8%) patients experienced ulceration.
      Ulceration occurred in 192 (9.8%) of 1960 [corrected] total hemangiomas.
      Hemangiomas with ulcerations were more likely large, mixed clinical type,
      segmental morphologic type, and located on the lower lip, neck, or anogenital
      region. Ulceration occurred at a median age of 4 months, most often during the
      proliferative phase. Children with ulcerated hemangiomas were more likely to
      present to a pediatric dermatologist at a younger age and to require treatment.
      Bleeding occurred in 41% of ulcerated lesions but was rarely of clinical
      significance. Infection occurred in 16%. CONCLUSIONS: Ulceration occurs in nearly
      16% of patients with infantile hemangiomas, most often by 4 months of age, during
      the proliferative phase. Location, size, and clinical and morphologic type are
      associated with an increased risk for development of ulceration.

PMID- 18035155
TI  - Toward family-centered inpatient medical care: the role of parents as
      participants in medical decisions.
AB  - OBJECTIVES: To determine parental participation in medical decision-making (MDM)
      during hospitalization and its association with parental self-efficacy and to
      explore other factors associated with participation. STUDY DESIGN: We surveyed
      parents of children admitted to a pediatric medical unit to measure parental
      report of participation in MDM during hospitalization and self-efficacy with
      physician interactions (categorized into tertiles). We performed multivariate
      logistic regression to evaluate the association between self-efficacy and
      parental participation, controlling for potential confounders. RESULTS: One
      hundred thirty of 278 eligible parents completed surveys and 86% reported
      participating in MDM about their child's care. After adjusting for covariates,
      parents with scores in the middle and highest self-efficacy tertiles had higher
      odds of participating in MDM compared with parents in the lowest tertile. Younger
      parents and parents of previously hospitalized children were also more likely to
      participate although parents with a high school education or less were less
      likely. CONCLUSIONS: Self-efficacy was significantly associated with parental
      participation in MDM during hospitalization after adjusting for confounding
      factors. Interventions to increase self-efficacy may also improve parental
      participation in MDM.

PMID- 18035156
TI  - A three-year-old with persistent hypokalemia.

PMID- 18035157
TI  - Clinical and molecular characteristics of staphylococcal skin abscesses in
      children.
AB  - Forty-nine children with skin abscesses (36 methicillin-resistant Staphylococcus
      aureus and 13 methicillin-susceptible S. aureus) exhibited similar disease
      severity. Both pathogen groups were pulse field type USA300, multilocus sequence
      type 8, and possessed Panton-Valentine leukocidin genes. Related microbial
      genetic architecture may account for similarities in disease severity despite
      differences in antibiotic susceptibility.

PMID- 18035158
TI  - Assessment of immunization status in hospitalized children followed by counseling
      of parents and primary care physicians improves vaccination coverage: an
      interventional study.
AB  - This prospective, intervention-control study in hospitalized, underimmunized
      children assessed the effect of vaccination reminders to parents during
      hospitalization and provides postdischarge rates of catch-up immunizations. One
      month after hospital discharge, significantly more children in the intervention
      group (27%) than the controls (8%) had received catch-up immunizations (P <
      .001).

PMID- 18035159
TI  - Infantile onset panniculitis with uveitis and systemic granulomatosis: a new
      clinicopathologic entity.
AB  - We report on 4 children with infantile-onset lobular panniculitis, high fever,
      uveitis, and systemic granulomatous inflammation, recruited through the
      International Registry of Pediatric Granulomatous Arthritis. Neither CARD15 nor
      CIAS1 mutations were found. Despite immunosuppressive therapy, disease course was
      progressive. Response to anti-tumor necrosis factor monoclonal antibody in 3
      patients is of note.

PMID- 18035160
TI  - Foam eater.

PMID- 18035161
TI  - Clinical policy: critical issues in the evaluation and management of adult
      patients presenting to the emergency department with syncope.

PMID- 18035163
TI  - Nurses were and are there.

PMID- 18035165
TI  - Compassion around the world.

PMID- 18035164
TI  - Response to "the difficult patient".

PMID- 18035166
TI  - The goodness and compassion of emergency nurses everywhere.

PMID- 18035167
TI  - Turning around the turn-arounds: improving ED throughput processes.

PMID- 18035168
TI  - Where in the world is ENA?

PMID- 18035169
TI  - Strengthening the care of the injured globally: the role of emergency nursing.

PMID- 18035170
TI  - A memorable Marine: the battle of coagulopathy.

PMID- 18035171
TI  - Severe hyperthermia in a 65-year-old man following sustained environmental heat
      exposure.

PMID- 18035173
TI  - US military nurses in wartime: reluctant heroes, always there.

PMID- 18035174
TI  - Safety benefits of a clinical pharmacist in the emergency department.

PMID- 18035175
TI  - Emergency preparedness response: building infrastructure.

PMID- 18035176
TI  - Asking the right question.

PMID- 18035178
TI  - You be the jury: was the standard of care met?

PMID- 18035179
TI  - Overdose and treatment of quetiapine ingestions.

PMID- 18035180
TI  - Penetrating renal trauma with delayed hemorrhage.

PMID- 18035181
TI  - How normal are "normal vital signs"? Effective triage of the older patient.

PMID- 18035183
TI  - Leptomeningeal metastasis.

PMID- 18035184
TI  - Desloratadine treatment for intermittent and persistent allergic rhinitis: a
      review.
AB  - BACKGROUND: Allergic rhinitis (AR) has a high prevalence and substantial impact
      on quality of life (QoL). The traditional classification of AR as either seasonal
      or perennial is being superseded in many countries by the ARIA (Allergic Rhinitis
      and its Impact on Asthma) definitions, in which the term intermittent AR denotes
      the presence of symptoms for <4 days a week or <4 weeks, and the term persistent
      AR denotes the presence of symptoms for >4 days a week for >4 weeks. These
      definitions, particularly that of persistent AR, may better reflect the true
      pattern of AR as it is experienced by patients. Desloratadine has been approved
      by the European Medicines Evaluation Agency for the treatment of intermittent and
      persistent AR, as defined by the ARIA classification. OBJECTIVE: The purpose of
      this review was to assess data concerning desloratadine in relation to the ARIA
      definitions of intermittent and persistent AR. METHODS: Relevant clinical studies
      and information on treatment guidelines were identified through searches of the
      English-language literature indexed on MEDLINE through May 2007. Search terms
      included intermittent AR, persistent AR, seasonal AR, perennial AR, and
      desloratadine. RESULTS: Desloratadine has been found to be effective and well
      tolerated in studies in subjects with symptoms of AR analogous to/consistent with
      the ARIA definitions of intermittent and persistent disease. In a 2-week,
      randomized, double-blind, placebo-controlled study in subjects with a > or =2
      year history of intermittent AR, desloratadine was associated with greater
      reductions relative to placebo in congestion scores (P < 0.05) and total symptom
      scores (TSS) (P <0.01). In a 4-week, multicenter, randomized, double-blind,
      placebo-controlled study in subjects with a > or =2-year history of perennial AR,
      desloratadine had greater efficacy than placebo in terms of reductions in TSS as
      early as day 2 (P > or = 0.02), as well as reductions in nasal and nonnasal
      symptom scores (P > or =0.04). A 4-week, randomized, double-blind, placebo
      controlled study assessing QoL found that desloratadine improved QoL scores to a
      greater extent than placebo in subjects with a > or =2-year history of perennial
      AR (P = 0.009). CONCLUSIONS: According to the ARIA guidelines, second-generation
      antihistamines are a cornerstone of pharmacologic therapy for AR. Desloratadine
      is effective in the treatment of AR across all classifications of disease, either
      seasonal/perennial or intermittent/persistent.

PMID- 18035185
TI  - Effects of renin-angiotensin system inhibition on end-organ protection: can we do
      better?
AB  - BACKGROUND: The renin-angiotensin system (RAS) is a major regulator of blood
      pressure (BP) and vascular response to injury. There is increasing evidence that
      RAS inhibition may provide end-organ protection independent of BP lowering. Two
      drug classes directly target angiotensin II through complementary mechanisms.
      Angiotensin-converting enzyme (ACE) inhibitors block the conversion of
      angiotensin I to the active peptide angiotensin II and increase the availability
      of bradykinin. Angiotensin receptor blockers (ARBs) selectively antagonize
      angiotensin II at AT 1 receptors and may also increase activation of the AT 2
      receptor and modulate the effects of angiotensin II breakdown products.
      OBJECTIVES: This paper presents an overview of clinical data supporting the use
      of RAS inhibitors (ACE inhibitors and ARBs) as monotherapy or combination therapy
      based on the known role of the RAS in BP regulation and the vascular response to
      injury, and considers the implications of the data for future treatment. METHODS:
      Relevant experimental and clinical studies were identified by searching MEDLINE
      (1969-June 30, 2007) using the primary search terms renin-angiotensin system,
      angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, and
      dual RAS blockade. Trials included in the review were large (>200 patients),
      prospective, randomized controlled studies evaluating the effect of RAS
      inhibition on end-organ protection in various high-risk populations. RESULTS:
      Eleven clinical trials each were identified that evaluated the effect of ACE
      inhibitor and ARB monotherapy on end-organ protection. Five trials were
      identified that evaluated the effects of combination therapy with an ACE
      inhibitor and an ARB compared with treatment with either agent alone in different
      patient populations using different end points. In hypertensive patients with
      type 2 diabetes and microalbuminuria, combination ACE-inhibitor/ARB therapy
      resulted in better BP control than either agent alone (mean difference, 11.2 mm
      Hg systolic [P = 0.002], 5.9 mm Hg diastolic [P = 0.003]), as well as greater
      reductions in microalbuminuria (mean difference in albumin:creatinine ratio, 34%;
      P = 0.04). Compared with monotherapy, dual RAS inhibition reduced the occurrence
      of a doubling of the serum creatinine concentration or end-stage renal disease by
      60% to 62% in patients with nondiabetic renal disease (P = 0.018 vs ACE inhibitor
      alone; P = 0.016 vs ARB alone). A recently published study reported a
      nonsignificant benefit for combination therapy over monotherapy only in a subset
      of hypertensive patients with high levels of microalbuminuria at baseline (58.1%
      vs 43.4% reduction, respectively). In patients with heart failure and left
      ventricular ejection fraction </=40%, the relative risk for cardiovascular death
      or hospitalization for heart failure was reduced by 15% in those who received an
      ARB added to an ACE inhibitor compared with those who received placebo added to
      an ACE inhibitor (P = 0.011). Another study found no benefit on mortality or
      cardiovascular end points with combination therapy compared with ACE-inhibitor
      monotherapy. Ongoing studies are investigating dual RAS blockade in patients at
      high risk for end-organ damage, as well as the most effective doses for use in
      combination regimens. CONCLUSIONS: There is accumulating evidence that
      antihypertensive regimens that inhibit the RAS may provide incremental end-organ
      protection. Combining ACE inhibitors and ARBs to provide more extensive RAS
      inhibition may provide greater antihypertensive efficacy and end-organ protection
      than use of either class alone. Future strategies for treating high-risk patients
      will focus on early interventions that prevent or delay end-organ damage.

PMID- 18035186
TI  - Comprehensive review of rasagiline, a second-generation monoamine oxidase
      inhibitor, for the treatment of Parkinson's disease.
AB  - BACKGROUND: Inhibitors of monoamine oxidase (MAO) with selectivity and
      specificity for MAO type B (MAO-B) prolong the duration of action of both
      endogenously and exogenously derived dopamine. Rasagiline [N-propargyl-l(R)
      aminoindan] is a second-generation propargylamine pharmacophore that selectively
      and irreversibly inhibits brain MAO-B and is specifically designed for the
      treatment of Parkinson's disease (PD). OBJECTIVE: The aim of this study was to
      review the pharmacology, tolerability, and clinical efficacy of rasagiline in the
      treatment of PD. METHODS: MEDLINE (1966-April 2007), the Cochrane Database of
      Systematic Reviews, and International Pharmaceutical Abstracts (1970-April 2007)
      were searched for original research and review articles published in English. The
      search terms were monoamine oxidase, neuroprotection, Parkinson disease,
      propargylamine, rasagiline, and selegiline. The reference lists of articles were
      also consulted, as was information provided by the manufacturer of rasagiline.
      RESULTS: Data from 63 clinical and laboratory studies were analyzed. Based on the
      results from those studies, we concluded that rasagiline PO QD, at the
      therapeutic dosage range of 0.5 to 1 rag/d, is effective and well tolerated and
      completely, selectively, and specifically inhibited MAO-B. Pharmacologically,
      rasagiline was found to be < or =10-fold more potent than selegiline and was not
      metabolized to amphetamine derivatives. Rasagiline was effective both as
      monotherapy in early PD and as adjunctive treatment in patients with advancing PD
      and motor fluctuations. As monotherapy, rasagiline provided modest yet clinically
      meaningful benefit. A randomized, double-blind, placebo-controlled study found
      that, after 26 weeks of treatment, the adjusted effect size for total Unified
      Parkinson's Disease Rating Scale score was -4.20 (95% CI, -5.66 to -2.73) for
      rasagiline 1 mg/d versus placebo (P < 0.001). Preliminary long-term data from an
      open-label study suggest a sustained therapeutic advantage when rasagiline is
      initiated early (before the need for dopaminergic agents) rather than later. In
      patients with more advanced disease who received treatment with dopaminergic
      agents, rasagiline and entacapone were associated with reductions of "off" time
      significantly greater than placebo (-1.18 and -1.2 vs 0.4 hour; both, P < or =
      0.001). Rasagiline was well tolerated in younger (aged <;70 years) and older
      (aged > or =70 years) patients with early or advanced PD. Pharmacologically,
      rasagiline has the potential to augment the vasopressor effects of diet-derived
      tyramine (ie, the "cheese reaction"). However, clinical challenge studies of
      tyramine have found this unlikely to occur even with ingestion of
      supraphysiologic amounts of tyramine. In experimental models, rasagiline has been
      found to have neuroprotective properties that may be independent of MAO-B
      inhibition. CONCLUSIONS: Based on this review, rasagiline has been found to be
      well tolerated and effective in the treatment of early PD and as adjunctive
      treatment in motor fluctuations. Whether rasagiline is associated with clinically
      significant neuroprotection (ie, disease modification) in PD is the subject of
      ongoing clinical trials.

PMID- 18035187
TI  - Ranibizumab for the treatment of neovascular age-related macular degeneration: a
      review.
AB  - BACKGROUND: Choroidal neovascular (wet) age-related macular degeneration (ARMD)
      is becoming more prevalent worldwide as life expectancy continues to increase.
      Ranibizumab for intravitreal injection is an inhibitor of human vascular
      endothelial growth factor A approved by the US Food and Drug Administration for
      the treatment of ARMD in June 2006. The actions of ranibizumab result in reduced
      cell proliferation, reduced formation of new blood vessels, and minimization of
      vascular leakage. OBJECTIVE: This paper reviews the pharmacologic and
      pharmacokinetic properties, clinical efficacy, and safety profile of ranibizumab,
      and pharmacoeconomic considerations associated with its use. METHODS: MEDLINE
      (1966-December 2006) and International Pharmaceutical Abstracts (1970-December
      2007) were searched for original research studies (Phase I, II, III, and IIIb),
      abstracts, and review articles concerning ranibizumab. The search terms were
      choroidal neovascularization, macular degeneration, Lucentis, ranibizumab,
      retinal degeneration, and vascular endothelial growth factor. Preference was
      given to Phase IlfllI studies. Selected information from the manufacturer of
      ranibizumab was also included. RESULTS: The efficacy of ranibizumab has been
      studied in 3 large clinical trials having the same primary efficacy end point,
      the proportion of patients losing <15 letters from baseline at 12 months (Early
      Treatment of Diabetic Retinopathy Study chart). A multicenter, Phase III,
      randomized, double-blind, sham-controlled, 24-month clinical trial evaluated
      ranibizumab 0.3 and 0.5 mg in 716 patients with minimally classic or occult
      choroidal neovascularization (CNV) associated with ARMD. The results for the
      primary efficacy end point were 94.5% and 94.6% in the ranibizumab 0.3- and 0.5
      mg groups, respectively, compared with 62.2% in the sham-injection group (P <
      0.001, both ranibizumab groups vs sham injection); at 24 months, the
      corresponding proportions were 92.0%, 90.0%, and 52.9% (P < 0.001, both
      ranibizumab groups vs sham injection). A 2-year, Phase I/II, single-masked
      (masked patient and visual acuity examiner, unmasked investigator), multicenter
      trial evaluated the tolerability and efficacy of the combination of ranibizumab
      0.5 mg and verteporfin photodynamic therapy (PDT) compared with verteporfin PDT
      alone in 162 patients with predominantly classic CNV. For the primary efficacy
      end point, the results were 90.5% for ranibizumab + PDT and 67.9% for PDT alone
      (P < 0.001). Receipt of ranibizumab + PDT was also associated with improved
      visual acuity, with 23.8% of patients gaining >15 letters from baseline, compared
      with 5.4% of those who received PDT alone (P = 0.003). Finally, an international
      Phase III, double-blind, active-controlled study compared ranibizumab 0.3 and 0.5
      mg with verteporfin PDT in 423 patients with predominantly classic lesions
      associated with CNV secondary to ARMD. For the primary efficacy end point, the
      results were 35.7% for ranibizumab 0.3 mg, 40.3% for ranibizumab 0.5 mg, and 5.6%
      for verteporfin PDT (P < 0.001). Serious adverse ocular events, which occurred in
      association with < 0.1% of intravitreal injections in these trials, included
      retinal detachment and endophthalmitis. Less serious adverse ocular reactions
      occurring in < 2% of patients included intraocular inflammation and increased
      intraocular pressure. CONCLUSION: The findings of these 3 large clinical trials
      suggest that ranibizumab was effective and well tolerated in patient.

PMID- 18035188
TI  - Posaconazole: an extended-spectrum triazole antifungal agent.
AB  - BACKGROUND: The incidence of invasive fungal infections (IFIs) caused by
      opportunistic filamentous molds is increasing, along with emerging fungal
      resistance. Posaconazole, a structural analogue of itraconazole that was approved
      for marketing in the United States in 2006, appears to be a promising antifungal
      agent. OBJECTIVE: This article provides an overview of the pharmacology,
      efficacy, and tolerability of posaconazole when used for the prophylaxis and
      treatment of various common and rare fungal infections. METHODS: Relevant
      information was identified through a search of MEDLINE (1966-April 2007),
      International Pharmaceutical Abstracts (1970-April 2007), and abstracts of the
      Interscience Conference on Antimicrobial Agents and Chemotherapy using the terms
      posaconazole and SCH 56592. Additional resources were found by searching the
      reference lists of the identified articles and the US Food and Drug
      Administration Web site. RESULTS: Posaconazole is available as an oral
      suspension. It is highly distributed to various sites, including bone, the
      central nervous system, and eye tissue. Its Vd is 2447 L when administered in
      multiple daily doses (up to 800 mg/d) in the presence of a high-fat meal. Because
      it is excreted mostly as unchanged drug in the feces (77%), posaconazole can be
      administered to patients with poor renal function without any dose adjustment.
      Posaconazole has shown in vitro and in vivo activity against a wide variety of
      fungi, including those that are rare and relatively resistant. Two clinical
      trials have compared posaconazole with fluconazole or itraconazole for the
      prophylaxis of IFIs in immunocompromised patients. The first, a randomized,
      double-blind trial in 600 recipients of hematopoietic stem cell transplants,
      found that overall rates of IFI did not differ significantly between posaconazole
      and fluconazole (5% vs 9%, respectively). The other, a randomized, open-label
      trial in 602 neutropenic patients, reported significantly fewer IFIs in patients
      receiving posaconazole compared with those receiving fluconazole or itraconazole
      (>2% vs >8%, respectively; P = 0.001). An additional 2 trials have investigated
      posaconazole for the treatment of oropharyngeal candidiasis (OPC) in patients
      with HIV infection. A randomized, controlled, evaluator-blinded study in 350 HIV
      infected patients with OPC found similar 14-day clinical success rates with
      posaconazole and fluconazole (91.7% and 92.5%, respectively; 95% CI, -6.6l to
      5.04), whereas an open-label study in 176 HIV-infected patients with a history of
      refractory OPC reported a 28-day clinical success rate of 75%. Numerous small
      studies and case reports have described successful posaconazole treatment of
      zygomycosis, aspergillosis, fusariosis, endemic dimorphic fungal infection, and
      superficial and subcutaneous fungal infections that were refractory to
      conventional antifungal agents or in patients who were unable to tolerate these
      agents. Posaconazole has been well tolerated. The most common complaints have
      been gastrointestinal in nature, including nausea (7%-8%) and diarrhea (3%-11%),
      although these have rarely led to permanent discontinuation of therapy. Other
      common adverse effects have included vomiting (4%-7%), headache (2%-8%), and
      liver enzyme elevations (2%-3%). CONCLUSIONS: Posaconazole suspension
      administered at up to 800 mg/d is a reasonable alternative to conventional
      antifungal agents for the prevention and treatment of IFIs in high-risk
      populations. It may also be suitable in patients with infections caused by rare
      or relatively resistant fungi, and those who are unable to tolerate long-term
      therapy with other antifungal agents.

PMID- 18035189
TI  - Nelarabine: a novel purine antimetabolite antineoplastic agent.
AB  - BACKGROUND: Nelarabine was approved by the US Food and Drug Administration (FDA)
      in October 2005 for the treatment of T-cell acute lymphoblastic leukemia (T-ALL)
      and T-cell lymphoblastic lymphoma (T-LBL) that has not responded to or has
      relapsed after treatment with at least 2 chemotherapy regimens. OBJECTIVES: This
      article reviews the pharmacology, mechanism of action, and pharmacokinetic and
      pharmacodynamic properties of nelarabine. Also reviewed are nelarabine's clinical
      efficacy in T-ALL, T-LBL, and other hematologic malignancies; its toxicity
      profile, dosage, and administration; and areas of ongoing and future research.
      METHODS: Relevant literature was identified through searches of MEDLINE (1966
      April 2007), International Pharmaceutical Abstracts (1970-April 2007), and the
      American Society of Hematology database (2003-2006) using the terms nelarabine,
      Arranon, 506U78, and 2-amino-6-methoxypurine arabinoside. The reference lists of
      the identified articles were searched for additional sources. Product information
      obtained from the manufacturer of nelarabine was consulted, as were the FDA
      reviews of nelarabine. All identified publications were considered, and those
      meeting the objectives of this review were included. RESULTS: Nelarabine, a
      soluble prodrug of 9-beta-D- arabinofuranosylguanine (ara-G), is a novel purine
      antimetabolite antineoplastic that preferentially accumulates in T-cells. Ara-G
      is rapidly phosphorylated in T-cells to ara-G triphosphate (ara-GTP), which
      exerts cytotoxic effects. Renal elimination of ara-G is decreased in patients
      with mild to moderate renal impairment; however, no dose adjustment is
      recommended. Accumulation of ara-GTP occurs in T-cells in a dose-dependent
      manner, leading to preferential cytotoxicity. Nelarabine has activity in T-cell
      malignancies, as evaluated in 2 Phase I and 5 Phase II studies. It received
      accelerated approval from the FDA based on the resuits of 2 Phase II trials, one
      in pediatric patients (PGAA 2001) and the other in adults (CALGB 19801). In PGAA
      2001, patients with T-ALL in first relapse (n = 33) had an objective response
      rate of 55% (16 with a complete response [CR] and 2 with a partial response
      [PR]), and those with T-ALL in second relapse (n = 30) had an objective response
      rate of 27% (7 CR and 1 PR). Among patients with central nervous system-positive
      T-ALL or T-cell non-Hodgkins lymphoma (T-NHL) (n = 21), 33% had an objective
      response (5 CR and 2 PR); among patients with T-ALL or T-NHL with extramedullary
      relapse (n = 22), 14% had a PR. CALGB 19801 included 39 adult patients with T
      cell malignancies, of whom 7 (18%) had a CR and an additional 2 (5%) had a CR
      without full hematologic recovery. The recommended dose of nelarabine in adults
      is 1500 mg/m(2) IV given over 2 hours on days 1, 3, and 5, repeated every 21
      days; the recommended dose in pediatric patients is 650 mg/m(2) IV given over 1
      hour for 5 consecutive days, repeated every 21 days. Dose-limiting toxicities
      observed in the Phase I and II trials included central and peripheral
      neurotoxicity. Symptoms of central neurotoxicity included somnolence, seizures,
      dizziness, confusion, and ataxia; symptoms of peripheral neurotoxicity included
      paresthesias, pain in the extremities, and peripheral neuropathy. CONCLUSIONS:
      Nelarabine is indicated for the treatment of T-ALL and T-LBL that has not
      responded to or has relapsed after treatment with at least 2 chemotherapy
      regimens. Objective response rates in Phase II clinical trials of nelarabine have
      ranged from 11% to 60%. Use of nelarabine is limited by potentially severe
      neurotoxicity.

PMID- 18035190
TI  - A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel
      group study of the efficacy and tolerability of combination therapy with
      rosiglitazone and sulfonylurea in African American and Hispanic American patients
      with type 2 diabetes inadequately controlled with sulfonylurea monotherapy.
AB  - BACKGROUND: Type 2 diabetes mellitus is twice as prevalent in African Americans
      and Hispanic Americans as in non-Hispanic whites. However, the effectiveness and
      safety profile of rosiglitazone maleate used as combination therapy with
      sulfonylureas in the management of diabetes and its effect on cardiovascular
      disease (CVD) biomarkers/parameters have not been studied in these populations.
      OBJECTIVE: The purpose of this study was to determine the efficacy and
      tolerability of the addition of rosiglitazone to a regimen of glyburide once
      daily in African American and Hispanic American patients with type 2 diabetes
      previously inadequately controlled with sulfonylurea monotherapy. METHODS: This
      randomized, double-blind, placebo-controlled, parallel-group study was conducted
      at 38 centers in the United States. Eligible patients were aged < or =21 years,
      had type 2 diabetes, a fasting plasma glucose (FPG) level > or =140 mg/dL, and a
      glycosylated hemoglobin (HbA(1c)) value > or =7.5%, and had been treated with
      sulfonylurea monotherapy for at least 2 months before screening. Patients were
      assigned to receive treatment with glyburide 10 or 20 mg/d plus rosiglitazone 8
      mg (GLY+RSG) or placebo (GLY+PBO) PO (tablets) QD for 24 weeks. The primary
      efficacy end point was the change from baseline in HbA(1c) after 24 weeks of
      treatment. Secondary end points included change in FPG; proportion of patients
      achieving HbA(1c) targets (<7.0% and <6.5%); and changes in biomarkers for CVD
      risk, including C-reactive protein (CRP), plasminogen activator inhibitor (PAI)-I
      activity, fibrinogen, tissue plasminogen activator (tPA) antigen, von Willebrand
      factor (vWF), soluble vascular cell adhesion molecule (sVCAM), lipoprotein
      associated phospholipase A 2 activity, and urinary albumin/creatinine ratio
      (UACR). Tolerability was assessed using physical examination, including vital
      sign measurement, clinical laboratory tests, and adverse event (AE) reports
      collected at each study visit. RESULTS: A total of 245 patients (101 African
      American and 144 Hispanic American) were enrolled. Demographic characteristics
      were comparable between the GLY+RSG and GLY+PBO groups: mean (SD) age (52 [11.9]
      vs 53 [10.4] years), HbA(1c) (9.2% [1.3%] vs 9.4% [1.4%]), sex (men/women,
      45.3%/54.7% vs 48.3%/51.7%), race (African American/Hispanic American,
      43.6%/56.4% vs 37.9%/62.1%), and mean (SD) weight (86.3 [18.8] vs 88.3 [19.4]
      kg). In the overall study population, treatment with GLY+RSG was associated with
      a significantly greater mean (95% CI) reduction from baseline in HbA(1c) compared
      with GLY+PBO (between-group Delta, -1.4% [-1.7% to -1.1%]; P < 0.001). When
      assessed by ethnicity, HbA(1c) values were significantly reduced with GLY+RSG
      compared with GLY+PBO in African American patients (between-group Delta, -1.4%)
      and in Hispanic American patients (between-group Delta, -1.5%) (both, P < 0.001),
      as were FPG levels (between-group Deltas, -3.1 mmol/L [57 mg/dL] and -3.8 mmol/L
      [-69 mg/dL], respectively; both, P < 0.001). With GLY+RSG, 9151 (17.6%) African
      American patients and 17/66 (25.8%) Hispanic American patients achieved HbA(1c)
      <7%, compared with 2/44 (4.5%) and 1/72 (1.4%) patients, respectively, who
      achieved this goal with GLY+PBO. Homeostasis model assessment estimates of
      insulin sensitivity and beta-cell function were significantly improved with
      GLY+RSG compared with GIX+PBO (between-group Deltas, 29.3% and 78.4%,
      respectively; both, P < 0.001). With regard to CVD biomarkers, there were
      potentially deleterious changes compared with baseline in the GLY+PBO group for
      CRP (+29.4%; P = 0.042), PAI-1 activity (+27.0%; P = 0.006), fibrinogen (+15.7%;
      P = 0.007), and sVCAM (+7.0%; P = 0.035), whereas there were no significant
      increases in these factors in the GLY+RSG group. In the GLY+RSG group, there were
      significant improvements in tPA (-17.8%; P < 0.001), vWF (-11.3%; P = 0.019), and
      UACR (-17.2%; P = 0.028) over 24 weeks' treatment, whereas there were no
      significant changes in any of these factors in the GLY+PBO group. As a result,
      significant treatment effects were observed for CRP (-29.2%; P = 0.019), tPA (
      18.4%; P < 0.001), vWF (-12.9%; P < 0.015), and UACR (-26.7%; P = 0.006) with
      GLY+RSG compared with GLY+PBO. The most frequently reported AEs with GLY+RSG were
      edema and weight increase (both 121121 [9.9%] patients) and with GLY+PBO were
      upper respiratory tract infection (18/124 [14.5%] patients). AEs were reported in
      83/121 (68.6%) patients in the GLY+RSG group, of which 6/121 (5.0%) were assessed
      as severe, compared with 70/124 ( 56.5 % ) patients who received GLY+PBO, of
      which 31124 (2.4%) were assessed as severe. CONCLUSION: Add-on rosiglitazone
      administered for 24 weeks was effective and well tolerated in these African
      American and Hispanic American patients with type 2 diabetes previously
      inadequately controlled on sulfonylurea monotherapy.

PMID- 18035191
TI  - A 6-week, multicenter, randomized, double-masked, parallel-group study comparing
      travoprost 0.004% to latanoprost 0.005% followed by 6-week, open-label treatment
      with travoprost 0.004%.
AB  - OBJECTIVE: The aim of this study was to compare the tolerability and efficacy of
      once-daily travoprost 0.004% versus latanoprost 0.005% for 6 weeks followed by 6
      weeks of once-daily travoprost 0.004% in decreasing intraocular pressure (IOP) in
      patients with open-angle glaucoma (OAG) or ocular hypertension (OH). METHODS:
      This multicenter, randomized, doublemasked, active-controlled, parallel-group
      trial was conducted at 32 centers across Latin America. Patients aged > or =18
      years with OAG or OH were randomly assigned to receive topical travoprost 0.004%
      or latanoprost 0.005% 1 drop QD (9 PM) for 6 weeks (masked phase). At 6 weeks,
      all patients were assigned to receive open-label travoprost 0.004% 1 drop QD (9
      PM) for 6 additional weeks (open-label phase). Study visits were scheduled at
      weeks 1, 2, 4, 6, 8, and 12. At each study visit, IOP was measured at 5 PM (+/-1
      hour; approximately 20 hours after study drug administration). IOP changes from
      baseline were combined (pooled) from the 1-, 2-, 4-, and 6-week data to provide a
      comparison between the 2 treatment groups. Ocular adverse events (AEs) were
      monitored using slit-lamp examination. RESULTS: A total of 302 patients were
      enrolled (travoprost group, 155 patients; latanoprost group, 147 patients). The
      mean (SD) age of the travoprost group was 61.9 (10.6) years; 60.6% were female;
      and 47.1% were white. The mean (SD) age of the latanoprost group was 60.5 (12.4)
      years; 62.6% were female; and 49.0% were white. Mean IOP values were not
      significantly different between the travoprost and latanoprost groups at baseline
      (24.7 vs 24.2 mm Hg) or 6 weeks; however, the between-group difference in
      reductions from baseline in pooled IOP during the masked phase of the study was
      statistically significant (-8.3 vs -7.5 mm Hg; P = 0.009). At weeks 6 and 12,
      mean lOP levels were 16.1 and 16.2 mm Hg, respectively, in the travoprost group
      and 16.4 and 16.1 mm Hg in the group that was switched from latanoprost to
      travoprost (all, P = NS). The most common ocular AEs that occurred with masked
      travoprost, latanoprost, and open-label travoprost were hyperemia (26.9%, 12.2%,
      and 5.3%, respectively), discomfort (3.2%, 3.4%, and 1.1%), and pruritus (4.5%,
      2.0%, and 2.1%). CONCLUSIONS: In this population of patients with OAG or OH, 6
      week treatment with travoprost 0.004% was associated with a significantly greater
      decrease from baseline in pooled IOP compared with latanoprost 0.005% 20 hours
      after administration. There were no significant differences between the 2 groups.
      Travoprost and latanoprost were well tolerated.

PMID- 18035192
TI  - Results of a phase III, 8-week, multicenter, prospective, randomized, double
      blind, parallel-group clinical trial to assess the effects of amlodipine
      camsylate versus amlodipine besylate in Korean adults with mild to moderate
      hypertension.
AB  - BACKGROUND: Amlodipine besylate has been used in Korea for the treatment of
      hypertension for >17 years, with well-established efficacy and tolerability.
      Amlodipine camsylate is a newer formulation developed for generic use. It has
      been assessed in terms of physical stability and pharmacokinetic and
      pharmacodynamic properties and been found to be effective in lowering blood
      pressure in preclinical and Phase I and II trials. However, to date, no studies
      have compared the clinical effectiveness of amlodipine camsylate and amlodipine
      besylate in treating hypertension. OBJECTIVE: This study was designed to
      determine the effectiveness and tolerability of amlodipine camsylate compared
      with amlodipine besylate in Korean patients with mild to moderate hypertension.
      METHODS: This Phase III, 8-week, prospective, randomized, double-blind, parallel
      group study was conducted in 13 cardiology centers across the Republic of Korea.
      Male and female Korean patients aged 18 to 75 years having uncomplicated, mild to
      moderate, essential hypertension (sitting diastolic blood pressure [SiDBP] 90
      <110 mm Hg) and receiving no antihypertensives in the 2 weeks before
      randomization were eligible. Patients were randomly assigned to receive oral
      treatment with amlodipine camsylate or amlodipine besylate. For the first 4
      weeks, patients received amlodipine 5 mg QD (morning). After 4 weeks, if either
      blood pressure was > or =140/ > or =90 mm Hg or SiDBP had not decreased by > or
      =10 mm Hg from baseline, the dose of amlodipine was increased to 10 mg QD for 4
      weeks. Trough blood pressure and heart rate were measured in duplicate with the
      patient in the sitting position at each clinic visit (baseline [week 0] and weeks
      4 and 8 of treatment); mean values were calculated and recorded. At weeks 4 and
      8, tolerability was assessed using history taking and laboratory analysis, and
      compliance was assessed using pill counts. The primary end point was change from
      baseline in SiDBP at week 8. Secondary end points were change from baseline in
      sitting systolic blood pressure (SiSBP) at week 8 in the total population and in
      the subgroup of patients who had previously received antihypertensive treatment
      versus those who had not. RESULTS: A total of 189 patients were enrolled (mean
      age, 53 years; 105 women, 84 men; mean body weight, 65.8 kg). One patient in the
      amlodipine camsylate group dropped out of the study at week 0 of treatment (this
      patient did not use any study medication) and was excluded from the modified
      intent-to-treat (ITT) analysis. Thus, 188 patients were treated and included in
      the ITT analysis (94 patients per treatment group; ITT analysis); 161 patients
      were included in the perprotocol (PP) analysis (n = 80 for amlodipine camsylate,
      n = 81 for amlodipine besylate) (14 patients in the amlodipine camsylate group
      and 13 patients in the amlodipine besylate group were excluded from the PP
      analysis due to consistent withdrawal or protocol violation). Mean (SD) SiSBP and
      SiDBP were significantly decreased from baseline in both groups (amlodipine
      camsylate, from 146.7 [12.3]/96.6 [5.4] to 127.9 [14.8]/83.4 [7.7] mm Hg [both, P
      < 0.001]; amlodipine besylate, from 146.8 [12.8]/96.7 [5.1] to 128.0 [10.1]/83.8
      [7.5] mm Hg [both, P < 0.001]). The differences in SiSBP/SiDBP between the 2
      groups at week 8 were not significant. The SiDBP response rates in the subgroups
      that had and had not been previously treated with antihypertensives were
      statistically similar (56/69 [81.2%] and 83/92 [90.2%], respectively). The
      prevalences of clinical adverse events (AEs) were not significantly different
      between the 2 treatment groups (amlodipine camsylate, 27.3 %; amlodipine
      besylate, 28.7%). The most common AEs were dizziness and dyspnea (both in 3/94
      [3.2%] and 1/94 [1.1%] patients who received amlodipine camsylate and amlodipine
      besylate, respectively). CONCLUSION: The effectiveness and tolerability of
      amlodipine camsylate were not significantly different from those of amlodipine
      besylate in these Korean adults with mild to moderate hypertension.

PMID- 18035194
TI  - Pooled analysis of two clinical trials comparing the clinical outcomes of topical
      ciprofloxacin/dexamethasone otic suspension and polymyxin
      B/neomycin/hydrocortisone otic suspension for the treatment of acute otitis
      externa in adults and children.
AB  - OBJECTIVE: This study aimed to compare the clinical outcome of patients receiving
      topical ciprofloxacin 0.3%/dexamethasone 0.1% (CD) otic suspension with that of
      those receiving polymyxin B/neomycin/ hydrocortisone (PNH) otic suspension for
      the treatment of acute otitis externa (AOE). METHODS: Data from 2 institutional
      review board-approved, multicenter, observer-masked, parallel-group, randomized,
      noninferiority clinical trials conducted at 76 institutions across the United
      States between April 1998 and July 1999 were pooled together for this analysis.
      Patients > or =1 year of age diagnosed with AOE were considered for inclusion in
      the studies. Patients with AOE >4 weeks' duration, a perforated tympanic
      membrane, chronic suppurative otitis media, or use of either antibiotics or
      steroids within the previous 7 days were excluded from the studies. Patients were
      randomly assigned to receive CD or PNH for 7 days. CD was administered as 3 drops
      in children and 4 drops in patients > or =12 years of age BID. PNH was
      administered as 3 drops in children and 4 drops in patients > or =12 years of age
      TID. The clinical investigators were blinded to treatment assignment. Due to the
      different dosing regimens, patients were not blinded, but they also were not
      directly informed of their treatment assignments. Otic inflammation, tenderness,
      edema, and discharge were clinically assessed on days 3, 8, and 18 of the
      studies. Otic inflammation and edema were evaluated using a 4-point scale (none =
      0; mild = 1; moderate = 2; and severe = 3). Otic tenderness and discharge were
      rated on a binomial scale (absent = 0 and present = 1). The clinical assessments
      were aggregated into a 9-point composite clinical scale (range, 0-8) to compare
      baseline severity between groups. For the final outcomes assessment in this
      study, the aggregated clinical scores were dichotomized into cured (0) versus
      noncured (>0) and analyzed using a Kaplan-Meier survival technique. A log-rank
      test was used to compare the cure curves between treatment groups. Kaplan-Meier
      summary statistics provide the mean and median times to cure, and the mean times
      to cure for the 25th and 75th patient quartiles. Tolerability was assessed by
      monitoring patients for adverse events at each visit. RESULTS: Data from 1072
      patients (1242 ears) were included in the analysis (CD, 537 patients; PNH, 535
      patients). Baseline AOE severity and demographic characteristics were similar
      between the 2 treatment groups. The mean patient age was 21.7 and 22.0 years in
      the CD and PNH groups, respectively. Both groups were similar with respect to
      sex, with 50.7% and 53.5% females in the CD and PNH groups, respectively. The
      racial composition was predominately white (88.6% vs 84.9% in the CD and PNH
      groups, respectively). The log-rank test revealed a significant difference in the
      AOE cure curves between the CD and PNH groups (P = 0.038). The proportions cured
      in the AOE at-risk groups at the day-3, -8, and -18 assessments in the CD and PNH
      treatment groups were 0.14 and 0.10, 0.75 and 0.72, and 0.98 and 0.97,
      respectively. The Kaplan-Meier summary statistics indicated that the mean time to
      cure was 0.6 day less with CD compared with PNH (9.7 vs 10.3 days). Treatment
      related adverse event rates were similar between the 2 groups and occurred in
      3.8% of the patients. The most common adverse events included otic pruritus
      (2.1%), otic congestion (0.6%), otic debris (0.5%), otic pain (0.3%),
      superimposed ear infection (0.3%), and erythema (0.1%). CONCLUSION: These data
      from 2 previous studies suggest that time to cure was significantly less with CD
      compared with PNH in patients with AOE.

PMID- 18035193
TI  - Effects of risedronate 5 mg/d on bone mineral density and bone turnover markers
      in late-postmenopausal women with osteopenia: a multinational, 24-month,
      randomized, double-blind, placebo-controlled, parallel-group, phase III trial.
AB  - BACKGROUND: Randomized clinical trials have shown that risedronate reduces the
      risk for both ver- tebral and nonvertebral fractures in postmenopausal women with
      osteoporosis (bone mineral density [BMD] T-score, <-2.5). If left untreated,
      osteopenia (T-score, between -1 and -2.5) may progress to osteo- porosis.
      Risedronate sodium, a pyridinyl bisphospho- nate, is an antiresorptive drug
      approved by the US Food and Drug Administration for the prevention and treatment
      of osteoporosis in postmenopausal women. Although the effects of risedronate in
      preventing frac- tures has been established, its effects in maintaining or
      increasing BMD in osteopenia have not. OBJECTIVE: In this clinical trial, the
      efficacy and tol- erability of risedronate in improving and maintaining BMD
      levels in late-postmenopausal women with os- teopenia were assessed. METHODS:
      This 24-month, randomized, double- blind, placebo-controlled, parallel-group,
      Phase III trial was conducted at 14 study centers across Finland, The
      Netherlands, Norway, Spain, and Sweden. Late- postmenopausal (> or =5 years from
      menopause) women with lumbar spine (LS) BMD T-score between -1 and -2.5 and the
      presence of > or =1 additional risk factor for osteo- porosis or proximal femur
      (Fern) BMD T-score < or = -1 were randomized to receive risedronate 5 mg (n =
      114) or placebo (n = 57) PO QD for 24 months. The primary efficacy end point was
      the percentage change from baseline in LS BMD at study end point (24 months or
      last observation carried forward). Secondary efficacy end points were the
      percentage changes from base- line in total proximal Fern BMD and 2 bone turnover
      markers-urinary type I collagen cross-linked N-telopeptide (uNTx) and serum bone
      specific alkaline phosphatase (sBAP)-at 12 months and study end point.
      Tolerability was assessed using reported adverse events (AEs), laboratory
      analysis, and physical exami- nation including vital-sign measurements. RESULTS:
      A total of 171 women were included (mean [SD] age, 65.9 [6.8] years; mean [SD] LS
      BMD T-score,-1.82 [0.42]; risedronate group, 114 patients; placebo group, 57). At
      study end point, LS BMD had significantly increased from baseline in the
      risedronate group (P < 0.05) but remained unchanged in the placebo group (mean
      [SE] %Delta, +4.49% [0.38%] and +0.05% [0.54%], respectively; P < 0.001). Between
      treatment differences in mean (SE) percentage changes from baseline in LS BMD
      and Fem BMD were signif- icant at 12 months and study end point (LS BMD, both P <
      0.001; Fem BMD, P = 0.002 and P < 0.001, respectively). At 12 months and study
      end point, ris- edronate use was associated with significantly reduced
      concentrations of uNTx and sBAP compared with placebo (both, P < 0.001).
      Risedronate treatment was well tolerated with regard to gastrointestinal AEs; the
      most frequent AEs in the risedronate group were hy- pertension (n = 13),
      constipation (n = 8), and hyper- cholesterolemia (n = 8). CONCLUSIONS: In these
      late-postmenopausal women with LS osteopenia and > or=1 additional risk factor or
      hip osteopenia, 24-month treatment with risedronate 5 mg/d was associated with
      the prevention of bone loss at the spine and hip (based on significant increases
      in BMD in the LS and total proximal Fem) and reduced bone resorption (based on
      significantly reduced concen- trations of uNTx and sBAP) and was well tolerated.

PMID- 18035195
TI  - Pharmacokinetic and pharmacodynamic properties of a single intravenous dose of
      ibutilide fumarate: a phase I, randomized, open-label, increasing-dose study in
      healthy Chinese men.
AB  - BACKGROUND: Atrial flutter is a common sustained atrial tachyarrhythmia whose
      frequency increases with age. Ibutilide is a class III antiarrhythmic agent used
      for the cardioversion of atrial flutter or atrial fibrillation. OBJECTIVE: This
      study assessed the pharmacokinetic (PK) and pharmacodynamic properties and
      tolerability of a single intravenous dose of ibutilide fumarate in healthy
      Chinese men. METHODS: This Phase I, randomized, open-label, increasing-dose trial
      was conducted at the Clinical Pharmacology Center, Cardiovascular Institute and
      Fu Wai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical
      College in Beijing, People's Republic of China. Healthy, nonsmoking men aged 18
      to 45 years and weighing within 15% of their ideal height/weight range were
      randomly assigned to 1 of 6 treatment groups: ibutilide 0.005, 0.01, or 0.02
      mg/kg, or 0.5, 0.75, or 1.0 mg. Each volunteer received a 10-minute infusion of
      ibutilide under fasting conditions. For analysis of PK properties, blood samples
      were obtained at the following times: immediately before administration of study
      drug; 3, 5, 8, 10, 30, and 60 minutes after administration; and 2, 4, 6, 8, 12,
      and 24 hours after administration. Plasma ibutilide concentrations were
      determined using a validated high- performance liquid chromatography method with
      tandem mass-spectrometric detection. Continuous electrocardiographic monitoring
      was performed, and 12-lead electrocardiograms were recorded before dosing and at
      defined times from the start of infusion until 24 hours after dosing.
      Tolerability was assessed throughout the study based on physical examinations,
      measurement of vital signs, laboratory analyses, and monitoring of adverse
      effects. RESULTS: Forty healthy Chinese men were enrolled (mean [SD] age, 24.0
      [3.9] years [range, 19-36 years]; mean [SD] body weight, 62.8 [7.9] kg [range, 48
      80 kg]). The plasma ibutilide end-of-infusion concentration and AUC(0-infinity)
      increased approximately linearly with increasing doses of ibutilide. No
      statistically significant differences in the principal PK parameters were found
      among dosage groups; t(1/2) ranged from 7.5 to 9.1 hours, systemic clearance from
      68 to 85 mL/min per kg, and Vd from 51 to 60 L/kg. The mean QTc interval was
      significantly increased during and after ibutilide infusion (baseline range, 406
      418 milliseconds; maximum range, 469-683 milliseconds; P < 0.05 vs baseline). The
      changes in QTc interval were dose dependent, and there was a significant
      correlation between plasma ibutilide concentrations and changes in the QTc
      interval (r = 0.7244; P < 0.01). There were no significant changes in blood
      pressure or the QRS and PR intervals. One volunteer complained of dizziness, but
      no other apparent adverse effects were observed. CONCLUSIONS: The results of this
      study in a selected population of healthy Chinese men suggest that the PK
      properties of ibutilide are linear with respect to dosing. A single intravenous
      dose of ibutilide prolonged the QTc interval in a dose- and concentration-
      dependent manner. Ibutilide was generally well tolerated.

PMID- 18035196
TI  - Phase I, double-blind, randomized, placebo-controlled, dose-escalation study of
      the effects on blood pressure of abrupt cessation versus taper down of guanfacine
      extended-release tablets in adults aged 19 to 24 years.
AB  - BACKGROUND: Guanfacine hydrochloride is an alpha(2a)-adrenoreceptor agonist found
      to be effective in the treatment of attention-deficit/hyperactivity disorder
      (ADHD). Because the available immediate-release formulation requires multiple
      daily dosing and has been associated with rebound hypertension on abrupt
      cessation, an extended-release (ER) formulation has been developed for study of
      efficacy and tolerability parameters in patients with ADHD. OBJECTIVE: This trial
      was primarily undertaken to determine the effect on blood pressure (BP) of abrupt
      cessation versus taper-down of guanfacine ER. METHODS: This Phase I, randomized,
      double-blind, placebo-controlled, dose-escalation trial was conducted at MDS
      Pharma Services, Lincoln, Nebraska. Male and female healthy young-adult (aged 19
      24 years) volunteers were included. Subjects were randomly assigned to receive
      guanfacine ER as follows. Abrupt-cessation and taper-down groups both received
      guanfacine ER at forced titration: 1 mg on days 1 to 4, 2 mg on days 5 to 8, 3 mg
      on days 9 to 12, and 4 mg on days 13 to 16. The abrupt-cessation group then
      received placebo daily on days 17 to 32. The taper-down group began the following
      taper-down schedule: 3 mg on days 17 to 20, 2 mg on days 21 to 24, 1 mg on days
      25 to 30, and placebo on days 31 to 32. Placebo was administered daily to the
      subjects in the placebo group (days 1-32). All doses were given in the morning.
      Tolerability was assessed before (at the 8-hour baseline visit), during
      (approximately every 4 days and during 48-hour confinements at days 17/18 and
      31/32), and 7 days after the study and included assessment of BP and pulse, 12
      lead electrocardiography (ECG), and laboratory assays. Adverse events (AEs) were
      also tracked every 4 days beginning on day 5 and 7, 14, and 30 days poststudy by
      recording responses and follow-up to a nonleading question about how the patient
      was feeling that day. RESULTS: Forty-five subjects were enrolled in the study (15
      in each group), and 35 subjects completed it. The mean age of study participants
      was 22 years, 87% were white, and the ratio of women to men was 2:1. There were
      no marked differences between groups regarding age, sex, or race. Compared with
      the taperdown group, the abrupt-cessation group did not exhibit a clinically
      significant elevation of systolic BP (SBP) or diastolic BP (DBP) or other
      tolerability parameters, including AEs. Significant differences in BP were
      observed on days 17/18 (first day of abrupt cessation) and 31/32, but the overall
      means were not statistically different. The SBP decreases were -7.55% (-8.84 mm
      Hg) in the abrupt-cessation group and -8.33% (-9.69 mm Hg) in the taper-down
      group. The DBP decreases were -9.14% (-6.17 mm Hg) in the abrupt-cessation group
      and -9.94% (-6.59 mm Hg) in the taper-down group. There were no statistically
      significant or clinically important differences in change or percentage change in
      pulse from baseline to day 31/32 between the taper-down and placebo groups (least
      squares mean difference, 2.26 bpm). None of the subjects experienced bradycardia.
      No clinically important treatment related trends were noted in the clinical
      laboratory, ECG, or physical examination findings, including vital signs. No
      serious treatment-emergent AEs were reported in this study. Overall, 124
      treatment-emergent AEs were reported in 29 (64%) subjects. Treatment-emergent AEs
      were reported in 14 (93.3%) of 15 subjects in the abrupt-cessation group, 8
      (53.3%) of 15 subjects in the taper-down group, and 7 (46.7%) of 15 subjects in
      the placebo group. Headache was the most common AE reported in the abrupt
      cessation (46.7%) and placebo (13.3%) groups. For the taper down group, it was
      dry mouth (26.7%). All AEs were classified as mild or moderate. CONCLUSION: In
      this small study group of healthy, young-adult volunteers, guanfacine ER at doses
      up to 4 mg/d was abruptly discontinued without significant increases in SBP or
      DBP or other tolerability parameters, including AEs, compared with taper.

PMID- 18035197
TI  - Effects of liposomal amphotericin B versus an amphotericin B lipid complex on
      liver histopathology in patients with hematologic malignancies and invasive
      fungal infections: a retrospective, nonrandomized autopsy study.
AB  - BACKGROUND: Abnormal liver function test (LFT) results are common in patients
      with hematologic abnormalities, making the assessment of drug-related
      hepatotoxicity difficult. Studies based on elevated LFT levels have found that
      use of liposomal amphotericin B (L-AMB) was associated with increased
      hepatotoxicity compared with amphotericin B (AMB)/deoxycholate or amphotericin B
      lipid complex (ABLC). Because LFT abnormalities are multifactorial in severely
      immunocompromised patients, uncertainty remains regarding the clinical
      significance of these laboratory findings. OBJECTIVE: The aim of this study was
      to present the hepatic histopathologic findings on autopsy in patients who had
      hematologic malignancies and fungal infections and had received L-AMB or ABLC.
      METHODS: This study was conducted at The University of Texas M.D. Anderson Cancer
      Center, Houston, Texas. Records from 1995 to 2004 of patients who had received L
      AMB or ABLC for > or =7 days, within 30 days before death, were reviewed by 1
      investigator. Hepatic autopsy slides were independently reviewed by another
      investigator (pathologist) in a blinded fashion. Histopathologic evidence of
      amphotericin-related hepatotoxicity was predetermined based on histopathologic
      abnormalities reported in animal studies (eg, macrophage vacuolation, multifocal
      hepatocellular necrosis). Based on data from animal studies and in view of the
      lack of studies in humans, multifocal necrosis, fatty infiltration, macrophage
      vacuolation, and/or "foamy macrophage" accumulation were all considered
      histopathologic abnormalities associated with the use of lipid formulations of
      AMB. RESULTS: Data from 64 patients were included (32 patients per group). The
      demographic characteristics were comparable between the ABLC and L-AMB groups
      (median ages, 47.5 and 53.0 years, respectively; male, 44% and 53%; white, 75%
      and 78%; median weight, 67 and 78 kg; active underlying malignancy, 84% and 78%).
      There were no significant between-group differences in cumulative dose (6 and 7
      g), median daily dose (both, 5 mg/kg), or median duration of treatment (19.5 and
      19.0 days). Abnormal results (>5 x from baseline) on LFT were found in 12 (38%)
      and 10 (31%) patients who received ABLC and L-AMB, respectively, but these
      findings were thought to be associated with concomitant use of triazoles (4/12
      [33%] and 1/10 [10%] patients, respectively), hepatotoxic antibiotics (8/12 [67%]
      and 5/10 [50%]), and/or other hepatotoxic medications (2/12 [17%] and 1/10
      [10%]). Nonspecific abnormalities were observed on histopathology in 94% of
      patients. There was no evidence of histopathologic abnormalities reported in
      animal toxicity studies of lipid AMB, such as macrophage vacuolation or
      multifocal hepatocellular necrosis. CONCLUSIONS: Although abnormal results on LFT
      and/or histopathologic changes in liver were found in 92% of these debilitated
      patients with hematologic malignancy, direct histopathologic evidence of toxicity
      associated with lipid formulations of AMB was not established in our study.

PMID- 18035198
TI  - Risk reduction and tolerability of fluvastatin in patients with the metabolic
      syndrome: a pooled analysis of thirty clinical trials.
AB  - OBJECTIVE: This pooled analysis of 30 completed clinical trials assessed the
      efficacy and safety profile in reducing cardiovascular disease (CVD) risk of
      fluvastatin in the treatment of dyslipidemia in patients with and without the
      metabolic syndrome (metS). METHODS: Data from 30 double-blind, randomized,
      placebo-controlled or fluvastatin-controlled trials with > or =6 weeks of active
      treatment and daily fluvastatin doses of 20, 40, and 80 mg were pooled. Patients
      received fluvastatin or placebo. Linear contrasts from an analysis of covariance
      model containing factors for trial and treatment group (immediate-release
      fluvastatin 20, 40, 80 mg; extended-release fluvastatin 80 rag; or placebo), and
      using the baseline value as covariate, were used to compare the percentage
      changes from baseline to the first postbaseline assessment of all lipid
      parameters. A Cox regression analysis compared the all-fluvastatin group to the
      placebo group with regard to the time to occurrence of clinical end points from 5
      pooled studies, each with a mean treatment duration >1 year wherein clinical end
      points were reviewed by an adjudication committee. These analyses were performed
      separately for patients with and without metS. RESULTS: This pooled analysis
      included data from 7043 patients (4095 men, 2948 women; all-fluvastatin group
      with and without metS, 2529 and 2052 patients, respectively; placebo group with
      and without metS, 1514 and 948 patients, respectively). Patients with metS in the
      pooled fluvastatin group had a greater mean reduction in triglyceride levels
      (24.1% vs 6.7%), a greater mean increase in high-density lipoprotein cholesterol
      levels (10.3% vs -0.6%), and a similar mean reduction in low-density lipoprotein
      cholesterol levels (26.8% vs 26.7%) compared with the subgroup of patients
      without metS. Treatment with fluvastatin was associated with a significantly
      lower incidence of major adverse cardiovascular events (MACEs) (16.4% vs 22.0%)
      and an increase in the time to first MACE in patients with metS compared with
      placebo (hazard ratio = 0.728; P = 0.001). The incidences of adverse events,
      particularly those of concern (ie, myalgia and/ or increased blood creatine
      phosphokinase, alanine aminotransferase, and/or aspartate aminotransferase) with
      lipid-lowering therapy, were statistically similar between the patients who
      received fluvastatin and those who received placebo in the 2 subgroups.
      CONCLUSION: The results from this pooled analysis found that fluvastatin was
      effective in reducing CVD risk in the treatment of dyslipidemia in these patients
      with metS.

PMID- 18035199
TI  - Effectiveness of erdosteine in elderly patients with bronchiectasis and
      hypersecretion: a 15-day, prospective, parallel, open-label, pilot study.
AB  - BACKGROUND: Mucus plugging and hypersecretion have been associated with an
      increased relative risk of death in patients with bronchiectasis who may or may
      not have chronic obstructive pulmonary disease (COPD), which is of prognostic
      relevance in the elderly. However, chest physiotherapy and/or the use of
      mucoactive agents is considered to be an effective therapeutic model in treating
      patients with COPD and bronchiectasis. OBJECTIVE: The objective of this study was
      to test the effectiveness of oral erdosteine in treating elderly patients with
      bronchiectasis and chronic mucus hypersecretion who have been referred to a
      pulmonary rehabilitation program. METHODS: In this 15-day, prospective, parallel,
      open label, pilot study, elderly patients with bronchiectasis, hypersecretion, a
      noncurrent smoking status, who had been consecutively enrolled at Ospedale Villa
      Pineta's Pulmonary Rehabilitation Center, Pavullo-Modena, Italy, were randomized
      into 2 treatment groups. Group 1 consisted of those patients receiving PO
      erdosteine 225 mg BID and chest physiotherapy; group 2 comprised those patients
      receiving chest physiotherapy alone. Forced lung volumes, arterial blood gases,
      respiratory muscle strength, walking capacity (as measured by 6-minute walking
      test [6MWT]), and visual analog scale (VAS) symptoms (cough and dyspnea) were
      recorded at enrollment and at the conclusion of the study. Mucus density (MD),
      mucus purulence (MP), and mucus volume produced (MVP) were assessed using a 3
      point scale (0 = best or low; 1 = moderate; and 2 = worst or high) at baseline
      and at 5-day time points during the study period. All measurements were assessed
      by personnel blinded and not directly associated with the study administration.
      RESULTS: Thirty patients (21 [70%] male and 9 [30%] female; mean [SD] age, 71
      [11] years; and mean [SD] weight, 66 [3] kg) were enrolled. Characteristics were
      similar in the 2 groups at baseline. At day 15, significant improvements were
      observed in 6MWT, VAS cough, and VAS dyspnea (P < 0.01) in both groups. However,
      a significant improvement in forced expiratory volume in 1 second and forced
      vital capacity (in milliliters) was observed only in group i (0.2 [0.3]; P <
      0.05). At day 15, improvement was observed in mean (SD) in MD, MP, and MVP scores
      for both groups. Significant changes, however, were observed in all 3
      measurements in group 1 (-0.80 [0.22], -0.71 [0.51], and 1.01 [0.39],
      respectively), whereas a significant improvement was observed only in MD (-0.55
      [0.44]) and MVP (0.45 [0.62]) in group 2. The improvement in MVP observed in
      group 1 was significantly better than that observed in group 2 (P < 0.05).
      CONCLUSION: This pilot study found that a regimen of PO erdosteine 225 mg BID in
      addition to routine chest physiotherapy provided some physiologic and clinical
      benefits in the treatment of these elderly patients with bronchiectasis and
      chronic mucus hyper-secretion.

PMID- 18035200
TI  - Dosing intervals and hemoglobin control in patients with chronic kidney disease
      and anemia treated with epoetin alfa or darbepoetin alfa: a retrospective cohort
      study.
AB  - BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD). The
      approved dosing interval for currently available erythropoiesis-stimulating
      agents (ESAs) is 2 to 3 times weekly for epoetin alfa (EPO) and every 1 to 2
      weeks for darbepoetin alfa (DARB). However, clinicians sometimes use less
      frequent dosing in the interest of convenience. OBJECTIVES: This study
      investigated patterns of actual ESA use (doses and dosing intervals) and hemoglo-
      bin (Hb) control in adult outpatients with CKD not requiring dialysis at the
      Cleveland Clinic Foundation anemia clinic. The distribution of and variability in
      Hb levels in these patients were also examined. METHODS: The clinical charts and
      electronic records of adult outpatients with CKD who initiated ESA therapy before
      March 2005 were reviewed to identify the initial, dominant (used for the longest
      consecutive period), and final dosing intervals and mean weekly doses of EPO and
      DARB. Hb control was examined in terms of maximum deviations >12 g/dL and <11
      g/dL, and the proportions of measurements outside these values. RESULTS: The
      analysis included data from 111 outpatients (mean [SD] age, 65.9 [14.4] years;
      53.2% male; 66.7% white, 29.7% black, 2.7% other, 0.9% unknown ethnicity). Twenty
      one patients received EPO only, 74 received DARB only, and 16 switched ESAs. The
      mean duration of follow-up was 20.5 months. The most common initial dosing
      intervals were qwk for EPO (66.7%) and q2wk for DARB (90.5%). The dominant dosing
      intervals were q2wk in 61.9% of EPO patients and q3wk in 62.3% of DARB patients.
      However, 80.0% of those who received EPO q2wk and 63.2% of those who received
      DARB q3wk eventually returned to their initial dosing intervals. The largest
      proportions of Hb mea- surements <11 g/dL occurred at dominant dosing intervals
      of qwk for EPO and q2wk for DARB (both, 46.0%; 11 and 26 patients, respectively),
      whereas the largest proportions of measurements >12 g/dL occurred with EPO dosed
      at q2wk (44.0%; 5 patients) and DARB dosed at >q4wk (62.0%; 5 patients).
      CONCLUSIONS: The patterns of ESA usage in adult outpatients with CKD at this
      center indicated that clinicians extended dosing intervals beyond those in the
      approved prescribing information. However, variations in Hb concentrations
      occurred during maintenance therapy administered at extended dosing intervals,
      resulting in the resumption of shorter dosing intervals in the majority of
      patients.

PMID- 18035201
TI  - A randomized, double-blind, placebo-controlled, two-period, crossover, pilot
      trial of lamotrigine in patients with central pain due to multiple sclerosis.
AB  - BACKGROUND: Approximately 30% of patients with multiple sclerosis (MS) have
      central pain (CP). The anticonvulsant lamotrigine has been shown to be
      efficacious in some types of CP, but its efficacy in MS-related CP has not been
      confirmed. OBJECTIVE: The aim of this pilot trial was to provide preliminary data
      for a planned larger trial. METHODS: A randomized, double-blind, placebo
      controlled, 2-period, crossover pilot study was conducted in a sample of patients
      aged > or =18 years with CP due to MS. The 2 treatment periods began with an 8
      week, double-blind titration period, during which the number of pills of study
      drug was increased until either total pain relief was achieved, 1 or more
      unmanageable adverse events were reported, or a maximum of 16 pills (400 mg of
      lamotrigine) were used daily. A 3-week maintenance period at the final prescribed
      amount was followed by a 2-week tapering period; there was a 2-week washout
      between the 2 treatment periods, after which patients were administered the
      alternate drug. Outcomes before, during, and after each study period were
      assessed using validated measures of pain and quality of life (the Brief Pain
      Inventory [BH], the Neuropathic Pain Scale [NPS], and the 54-item MS Quality of
      Life [MSQOL-54] questionnaire). Throughout the trial, patients completed a daily
      diary consisting of questions from the BPI-Short Form, as well as questions about
      the use of other analgesic drugs, changes in health, and the occurrence of
      adverse events. The BPI and NPS were completed weekly during telephone calls with
      the research coordinator, and the MSQOL-54 was administered during clinic visits
      (ie, visits at screening, baseline, end of period 1, and termination). The
      primary outcome measure was the mean pain intensity score during the final
      maintenance week of each of the 2 study periods. RESULTS: A total of 12 patients
      were enrolled and completed at least the first period of the study. Ten patients
      were women. The mean (SD) age was 49.3 (11.7) years, and the mean (SD) weight was
      76.5 (19.9) kg. The analysis revealed no significant differences between the
      lamotrigine and placebo periods in any of the study outcomes related to pain or
      quality of life. Regarding adverse events, 1 patient developed a moderate rash
      during the study, but the physician attributed this lesion to herpes zoster; this
      patient completed the study. While other adverse events were mild, 2 patients
      were withdrawn from the study after experiencing adverse events during the first
      study period; 1 had been receiving lamotrigine and the other placebo. CONCLUSION:
      The results from this pilot trial did not support either the use of lamotrigine
      in patients with MS-related CP or the need for a larger trial.

PMID- 18035202
TI  - Full results of the Evidence of Interferon Dose-Response-European North American
      Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor
      blinded comparison of low-dose weekly versus high-dose, high-frequency interferon
      beta-1a for relapsing multiple sclerosis.
AB  - BACKGROUND: Interferon (IFN)-beta therapy represents an important advance in the
      management of relapsing multiple sclerosis (MS), but information about the
      relative benefits and risks of available preparations is limited. OBJECTIVE: This
      report describes the full results of the Evidence of Interferon Dose-response
      European North American Comparative Efficacy (EVIDENCE) study, combining analyses
      that were previously reported in separate publications for different phases of
      the study. METHODS: The EVIDENCE study was a multicenter, randomized, assessor
      blinded comparison of 2 IFN-beta dosing regimens. In the study, patients with
      relapsing MS were randomly assigned to SC IFN-beta1a 44 lag TIW (Rebif, Serono
      Inc., Geneva, Switzerland) or IM IFN-betala 30 mug QW (Avonex, Biogen Idec,
      Cambridge, Massachusetts) for 1 to 2 years. The primary clinical end point during
      the comparative phase was the proportion of patients who remained free from
      relapses; secondary and tertiary clinical end points included the annualized
      relapse rate and time to first relapse, re- spectively. All clinical and magnetic
      resonance imaging (MRI) evaluations were performed by blinded assessors. In the
      crossover phase of the study, patients who were originally randomized to low-dose
      QW treatment switched to the high-dose TIW treatment for an additional 8 months.
      Adverse events were determined by spontaneous reporting and monthly laboratory
      testing during the comparative phase. RESULTS: A total of 677 patients were
      enrolled in the study and evenly randomized to treatment; 605 patients completed
      the comparative phase and 439 completed the crossover phase. During the
      comparative phase, a significantly higher proportion of patients in the high-dose
      TIW treatment group remained free from relapses when compared with patients in
      the low-dose QW treatment group (adjusted odds ratio, 1.5; 95% CI, 1.1-2.0; P =
      0.023). The high-dose TIW regimen was also associated with a significant
      reduction in the annualized relapse rate (-17%; P = 0.033) and a prolonged time
      to first relapse (hazard ratio, 0.70; P = 0.002). MRI measures of disease
      activity were significantly reduced in the high-dose TIW group compared with the
      low-dose QW treatment. During the crossover phase, a 50% reduction in mean
      relapse rates was observed in patients who converted from low-dose QW treatment
      to high-dose TIW treatment (P < 0.001), with significant concomitant reductions
      in MRI activity. Injection-site reactions were significantly more common with
      high-dose TIW treatment than with low-dose QW treatment (85% vs 33%; P < 0.001).
      Neutralizing antibody formation was more common with high-dose TIW treatment than
      with low-dose QW treatment (26% vs 3%; P < 0.001). CONCLUSIONS: The comparative
      phase of the EVIDENCE study found that treatment of MS with SC IFN-beta1a 44
      microg TIW was associated with a significant reduction in clinical and imaging
      measures of disease activity over 1 to 2 years, when compared with IM IFN-betala
      30 microg QW treatment. The crossover phase found that patients who changed from
      low-dose QW treatment to high-dose TIW treatment experienced enhanced benefits of
      treatment without a substantial increase in adverse events.

PMID- 18035203
TI  - Evaluation of the bioequivalence of single 100-mg doses of two oral formulations
      of cyclosporin A microemulsion: a randomized, open-label, two-period crossover
      study in healthy adult male Mexican volunteers.
AB  - BACKGROUND: Cyclosporin A is widely used in Mexico as immunosuppressive therapy
      in organ transplantation and in the treatment of autoimmune disorders. Although
      several generic oral formulations of cyclosporin A are available in Mexico,
      information concerning the bioequivalence of these formulations in the Mexican
      population is not available in the published literature. OBJECTIVE: The aim of
      this study was to compare the bioequivalence and tolerability of a generic (test)
      and a branded (reference) soft-gelatin capsule formulation of cyclosporin A
      microemulsion 100 mg available in Mexico. METHODS: This randomized, open-label, 2
      period cross-over study was performed at the Universidad Autonomade Nuevo Leon,
      Monterrey, Mexico. Eligible subjects were healthy male volunteers who were
      randomly assigned to receive a single 100-mg dose of the test or reference
      formulation, followed by a 2-week 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), AUC(0-t), and AUC(0
      infinity) , blood samples were obtained at intervals over the 48-hour period
      after dosing. The formulations were considered bioequivalent if the log
      transformed ratios of Cma x and AUC were within the predetermined equivalence
      range (80%-125%). Tolerability was assessed by monitoring vital signs and
      laboratory tests (hematology, blood biochemistry, hepatic function, and
      urinalysis), and by questioning subjects about adverse events. RESULTS: Thirty
      six male subjects (mean age, 22.08 years [range, 18-29 years]; mean weight, 78.23
      kg [range, 72-89 kg]; mean height, 177 cm [range, 169-185 cm]) were enrolled in
      the study, and 34 (17 each randomized to receive the test or reference
      formulation first) completed it. No period or sequence effect was observed. The
      90% CIs for the log-transformed ratios of C(max), AUC(0-t), and AUC(0-infinity)
      were 85.12 to 92.85, 92.14 to 99.75, and 92.19 to 99.72, respectively (all, P
      <0.05). Similar results were found for the data without log-transformation. No
      adverse events occurred or were reported by patients during the study.
      CONCLUSIONS: In this small study in healthy adult male Mexican volunteers, a
      single 100-mg dose of the test formulation was bioequivalent to a single 100-mg
      dose of the reference formulation based on the regulatory definition (rate and
      extent of absorption). Both formulations were well tolerated.

PMID- 18035204
TI  - Assessing compliance, acceptance, and tolerability of teriparatide in patients
      with osteoporosis who fractured while on antiresorptive treatment or were
      intolerant to previous antiresorptive treatment: an 18-month, multicenter, open
      label, prospective study.
AB  - BACKGROUND: Teriparatide (parathyroid hormone [1-34] [ribosomal DNA origin])
      stimulates new bone formation on trabecular and cortical (periosteal and/or
      endosteal) bone surfaces by preferential stimulation of osteoblastic activity
      over osteoclastic activity. It has been found to significantly reduce vertebral
      fractures by 65%, and nonvertebral fragility fractures by 53% in treatment-naive
      postmenopausal women who have previously suffered a vertebral fracture.
      OBJECTIVE: This study examined the compliance, acceptance, and adherance of SC
      teriparatide 20 pg QD. METHODS: In this 18-month, multicenter, openlabel,
      prospective study, women with postmenopausal osteoporosis, and men >30 years of
      age with either idiopathic or hypogonadal osteoporosis (with low bone mass [T
      score of -1 or worse] and > or =1 fragility fracture), who had experienced a
      treatment-related adverse event (AE) or an inadequate response while receiving
      antiresorptive treatment, and who were willing to receive open-label teriparatide
      for > or =18 months were eligible. Compliance was defined as self-reported use of
      > or =80% of study medication. Acceptance of the injection pen was determined by
      scores obtained from questionnaires and rating scales measuring patients'
      perception. Patients self-reported on injection discomfort, ease of use, and the
      overall injection administration. Acceptance was assessed at baseline, and 3, 6,
      and 18 months. AEs were recorded at each clinical visit from the patients' self
      reports. At the 3-month visit, a serum calcium level was drawn > or =16 hours
      after the previous teriparatide dose. RESULTS: In this study, 116 patients-102
      women with postmenopausal osteoporosis and 14 men (12 with idiopathic
      osteoporosis and 2 with hypogonadal osteoporosis)-were assessed for inclusion in
      the study. The mean (SD) age was 68.8 (11.1) years (range, 40-89 years) and the
      mean (SD) weight was 60.5 (11.7) kg (range, 37-87 kg). Seventy-three percent of
      the patients in this study had baseline spinal T-scores < or =-2.5, and 72% had
      fractured during treatment with an osteoporosis medication. Reported compliance
      was 89% at 6 months and 82% at 18 months. At baseline, 42% of patients were
      concerned about injection discomfort, and 43% were somewhat concerned with daily
      injections, while 7% were quite concerned. At 6 months, most patients reported
      much less concern (49%) or no concern (42%). Patient perceptions associated with
      learning how to use the pen injection, attaching the needle, holding the pen, and
      injecting the dose, improved during the first 6 months of the study. The most
      commonly reported AEs were dizziness, 12 (10.3%); nausea, 12 (10.3%); back pain,
      9 (7.8%); and muscle cramps, 9 (7.8%). No AEs were believed to be associated with
      the use of the pen injection or teriparatide. Five patients had mildly elevated
      serum calcium concentrations (maximum value 2.8 mmol/L) at 3 months. However, all
      were normal on repeat testing approximately 4 weeks thereafter. CONCLUSIONS: This
      study found that teriparatide pen injection was well accepted in these patients,
      and acceptance rates improved during the first 6 months of treatment and,
      thereafter, improved slightly for approximately 18 months. Reported compliance
      remained high throughout the study (82%-89%). Teriparatide pen injection was a
      viable treatment in these osteopenic or osteoporotic patients with fragility
      fractures.

PMID- 18035205
TI  - Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain
      associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension
      trial.
AB  - BACKGROUND: Central neuropathic pain (CNP), pain initiated or caused by a primary
      lesion or dysfunction of the central nervous system, occurs in ~28% of patients
      with multiple sclerosis (MS). Delta(9)-Tetrahydrocannabinol/cannabidiol
      (THC/CBD), an endocannabinoid system modulator, has demonstrated efficacy for up
      to 4 weeks in randomized controlled trials in the treatment of CNP in patients
      with MS. OBJECTIVE: The purpose of this extension was to establish long-term
      tolerability and effectiveness profiles for THC/CBD (Sativex (R), GW
      Pharmaceuticals plc, Salisbury, United Kingdom) oromucosal spray in CNP
      associated with MS. METHODS: This uncontrolled, open-label trial was an
      indefinite-duration extension of a previously reported 5-week randomized study in
      patients with MS and CNP. In the initial trial, patients were randomized to
      placebo or THC/CBD. Patients were only required to maintain their existing
      analgesia in the randomized study. In the open-label trial they could vary their
      other analgesia as required. All patients (placebo and THC/CBD) who completed the
      randomized trial commenced the open-label follow-up on THC/CBD (27 mg/mL: 25
      mg/mL). Patients titrated their dosage, maintaining their existing analgesia. The
      primary end point of the trial was the number, frequency, and type of adverse
      events (AEs) reported by patients. Secondary end points included changes from
      baseline in 11-point numerical rating scale (NRS-11) neuropathic pain score,
      hematology and clinical chemistry test results, vital signs, trial drug usage,
      and intoxication visual analogue scale scores. RESULTS: Sixty-six patients were
      enrolled in the randomized trial; 64 (97%) completed the randomized trial and 63
      (95%) entered the open-label extension (race, white, 100%; sex, male, 14 [22%];
      mean [SD] age, 49 [8.4] years [range, 27-71 years[). The mean (SD) duration of
      open-label treatment was 463 (378) days (median, 638 days; range, 3-917 days),
      with 34 (54%) patients completing >1 year of treatment with THC/CBD and 28 (44%)
      patients completing the open-label trial with a mean (SD) duration of treatment
      of 839 (42) days (median, 845 days; range, 701-917 days). Mean NRS-11 pain scores
      in the final week of the randomized trial were 3.8 in the treatment group and 5.0
      in the placebo group. In the 28 (44%) patients who completed the 2-year follow
      up, the mean (SD) NRS-11 pain score in the final week of treatment was 2.9 (2.0)
      (range, 0-8.0). Fifty-eight (92%) patients experienced > or =1 treatment-related
      AE. These AEs were rated by the investigator as mild in 47 (75%) patients,
      moderate in 49 (78%), and severe in 32 (51%). The most commonly reported AEs were
      dizziness (27%), nausea (18 %), and feeling intoxicated (11%). Two treatment
      related serious AEs (ventricular bigeminy and circulatory collapse) were judged
      to be treatment-related. Both serious AEs occurred in the same patient and
      resolved completely following a period of discontinuation. Eleven (17%) patients
      experienced oral discomfort, 4 persistently. Regular oral examinations revealed
      that 7 (11%) patients developed white buccal mucosal patches and 2 (3%) developed
      red buccal mucosal patches; all cases were deemed mild and resolved. Seventeen
      (25%) patients withdrew due to AEs. The mean number of sprays and patients
      experiencing intoxication remained stable throughout the follow-up trial.
      CONCLUSIONS: THC/CBD was effective, with no evidence of tolerance, in these
      select patients with CNP and MS who completed approximately 2 years of treatment
      (n = 28). Ninety-two percent of patients experienced an AE, the most common of
      which were dizziness and nausea. The majority of AEs were deemed to be of mild to
      moderate severity by the investigators.

PMID- 18035206
TI  - Pharmacokinetics and tolerability of rabeprazole sodium in subjects aged 12 to 16
      years with gastroesophageal reflux disease: an open-label, single- and multiple
      dose study.
AB  - OBJECTIVE: This study was conducted to characterize the pharmacokinetic and
      safety profile of rabeprazole sodium tablets in children and adolescents with
      gastroesophageal reflux disease (GERD). METHODS: This was a multicenter, open
      label, single- and multiple-dose study in subjects aged 12 to 16 years with GERD.
      Subjects were stratified by age (12-<14 years and 14-16 years) and were
      randomized to receive oral rabeprazole 10 or 20 mg/d over 5 or 7 days (to
      accommodate weekends). The pharmacokinetic parameters calculated included C(max),
      T(max), AUC, t(1/2), and apparent oral clearance (day 5/7 only). Blood samples
      for pharmacokinetic determinations were obtained on study days 1, 2, and 5 (or 7)
      and at discharge on day 6 (or 8). Safety assessments, including adverse events
      (AEs), were performed at all study visits. RESULTS: Twenty-four subjects were
      enrolled in the study (12 in each dose group); they were predominantly white, had
      a mean age of 14.2 years, and had a mean body mass index of 24.3 kg/m(2) (the
      90th percentile for adolescents of this age in the United States). Mean age and
      weight did not differ significantly between the 2 dose groups. On day 1, C(max)
      was significantly greater in the rabeprazole 20-mg group compared with the
      rabeprazole 10-mg group (P = 0.024); on day 5/7, both AUC and C(max) were
      significantly greater in the rabeprazole 20-mg group compared with the
      rabeprazole 10-mg group (P = 0.005 and P = 0.007, respectively). Within-period
      comparisons for both groups indicated that the AUC and C(max) for rabeprazole and
      its thioether metabolite did not differ significantly from day 1 to day 5/7. In
      addition, the T(max) and t(1/2) were relatively unchanged from day 1 to day 5/7
      in both dose groups. Treatment-emergent signs and symptoms occurred in 11
      subjects, 6 in the 10-mg group and 5 in the 20-mg group. The most frequently
      reported AEs were headache and nausea (16.7% and 8.3%, respectively). No
      statistically significant differences were observed between dose groups in terms
      of the number of subjects with AEs. CONCLUSIONS: Rabeprazole 10 and 20 mg were
      well tolerated in these children and adolescents with GERD. The results of the
      pharmacokinetic analyses of single and multiple oral doses indicated no apparent
      accumulation of rabeprazole or its thioether metabolite with the 10-mg dose.
      There was, however, a suggestion of accumulation with multiple dosing of
      rabeprazole 20 mg, which requires confirmation in larger studies.

PMID- 18035208
TI  - Cost-effectiveness of pegaptanib compared to photodynamic therapy with
      verteporfin and to standard care in the treatment of subfoveal wet age-related
      macular degeneration in Canada.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is characterized by loss of
      central vision and is the leading cause of blindness among persons over the age
      of 50 years in Canada. The wet form of AMD has 3 subtypes-occult, minimally
      classic, and predominantly classic. Photodynamic therapy (PDT) with verteporfin
      is indicated only for the category of predominantly classic wet AMD. Currently,
      there are no treatments available for the other AMD subtypes. Pegaptanib sodium
      was the first pharmacologic therapy approved in Canada for the treatment of
      subfoveal wet AMD regardless of subtype. OBJECTIVE: The aim of this study was to
      examine the cost-effectiveness of pegaptanib versus PDT with verteporfin and
      versus standard care for the treatment of subfoveal wet AMD in patients aged 65
      years in Canada. METHODS: A Markov model based on visual acuity in the better
      seeing eye was developed. Clinical efficacy was taken from the clinical trials.
      Costs of treatment, comorbidities (eg, depression, fractures, need for assisted
      living), vision rehabilitation, visual aids, and adverse events were considered.
      Costs, utilities, and mortality were estimated from data from the available
      published literature. Costs were reported in 2004 Canadian dollars, and costs and
      outcomes were discounted at 3% per annum. Lifetime costs, quality-adjusted life
      years (QALYs), and vision years gained (VYGs) were estimated. Sensitivity
      analyses were performed to determine model robustness. RESULTS: Patients who
      received pegaptanib experienced more QALYs gained (4.17) and VYGs (3.83) compared
      with patients who received PDT (3.87 and 3.01, respectively) or standard care
      (3.96 and 3.26). Mean total costs per patient were greater in patients who
      received pegaptanib compared to those who received PDT or standard care ($20,016
      vs $15,345 or $7669, respectively). The incremental cost per QALY in patients
      receiving pegaptanib compared to those receiving PDT was $49,052 and $59,039 for
      patients receiving pegaptanib versus standard care. The incremental cost per VYG
      was $20,401 and $21,559 with pegaptanib versus PDT and standard care,
      respectively. Sensitivity analyses found that the model was relatively robust to
      changes in various model parameters. CONCLUSION: The results of this analysis
      suggest that in Canada, pegaptanib is a cost-effective treatment for subfoveal
      wet AMD in elderly patients, regardless of lesion subtype, compared to PDT with
      verteporfin and to standard care.

PMID- 18035209
TI  - A population-based analysis of statin utilization in British Columbia.
AB  - OBJECTIVE: The purpose of this research was to measure prevalent and incident
      statin use in the population of British Columbia from 1996 to 2004 across
      specific patient characteristics (sociodemographic and clinical). METHODS: Statin
      utilization and demographic data were assessed with the use of prescription drug
      claims. Medical and hospital claims for statin users were examined for evidence
      of ischemic heart disease (IHD), diabetes mellitus (DM), atherosclerosis,
      cerebrovascular disease, peripheral vascular disease (PVD), and disorders of
      lipid metabolism during the 3 years before the first statin prescription.
      RESULTS: Statin prevalence increased from 1996 to 2004 (1.28 %-6.59%). The
      greatest use was among those aged 65 to 84 years. Prevalent use of atorvastatin,
      simvastatin, and rosuvastatin increased over time. There were 211,964 new statin
      users between 1999 and 2004. Quarterly incident statin use increased over time
      from 1999 to 2004 (0.29%-0.49%). A socioeconomic gradient, whereby use was
      greater in those with low socioeconomic status, was observed for incident statin
      use. Incident atorvastatin use increased over time; simvastatin, cerivastatin,
      and rosuvastatin peaked and then declined; and new use of other statins
      decreased. Among 211,964 incident statin users, 74,542 (35.17%) had evidence of
      IHD only; 43,257 (20.41%) had DM but no IHD; 9781 (4.61%) had no DM or IHD but
      had atherosclerosis, cerebrovascular disease, or PVD; 47,634 (22.47%) had
      disorders of lipid metabolism only; and 36,750 (17.34%) had none of the medical
      conditions evaluated. CONCLUSIONS: Prevalent use (1996-2004) and incident use
      (1999-2004) of statins in an entire population have increased dramatically.
      Although many statin users (60.19%) had evidence of medical conditions that
      indicate appropriate statin use, 39.91% of users were at low risk for
      cardiovascular disease, and therefore the benefit of statins in this group
      remains small.

PMID- 18035210
TI  - Radiotherapy in setting of collagen vascular disease.

PMID- 18035211
TI  - Cardiac exposures in breast cancer radiotherapy: 1950s-1990s.
AB  - PURPOSE: To estimate the doses to the heart and coronary arteries from common
      breast cancer radiotherapy (RT) regimens used worldwide from the 1950s to the
      1990s. METHODS AND MATERIALS: Virtual simulation and computed tomography planning
      were used to reconstruct the megavoltage and electron regimens. Manual planning
      was used for the orthovoltage and brachytherapy regimens. Several sources of
      variability associated with the dose estimates were assessed. RESULTS: Breast or
      chest wall RT resulted in whole heart doses of 0.9-14 Gy for left-sided and of
      0.4-6 Gy for right-sided irradiation. Internal mammary chain RT delivered heart
      doses of 3-17 Gy and 2-10 Gy for left- and right-sided irradiation, respectively.
      For most regimens, the dose to the left anterior descending coronary artery was
      greater than the heart dose. Scar boost, supraclavicular fossa, and axillary RT
      delivered mean cardiac doses of <or=3 Gy. The greatest source of variability in
      estimating dose from a given regimen was patient anatomy. CONCLUSION: For most
      techniques, the greatest radiation doses were received by the anterior part of
      the heart and the left anterior descending coronary artery, a common site of
      atherosclerosis causing myocardial infarction. Irradiation of these structures
      might have contributed to the excess risk of death from heart disease seen after
      some past breast cancer RT regimens.

PMID- 18035212
TI  - Glucagon-like peptide-2 improves both acute and late experimental radiation
      enteritis in the rat.
AB  - PURPOSE: Acute and/or chronic radiation enteritis can develop after radiotherapy
      for pelvic cancers. Experimental and clinical observations have provided evidence
      of a role played by acute mucosal disruption in the appearance of late effects.
      The therapeutic potential of acute administration of glucagon-like peptide-2 (GLP
      2) against acute and chronic intestinal injury was investigated in this study.
      METHODS AND MATERIALS: Intestinal segments were surgically exteriorized and
      exposed to 16.7 or 19 Gy X-rays. The rats were treated once daily with vehicle or
      a protease-resistant GLP-2 derivative for 14 days before irradiation, with or
      without 7 days of GLP-2 after treatment. Macroscopic and microscopic observations
      were made 2 and 15 weeks after radiation exposure. RESULTS: In the control
      animals, GLP-2 induced an increase in intestinal mucosal mass, along with an
      increase in villus height and crypt depth. GLP-2 administration before and after
      irradiation completely prevented the acute radiation-induced mucosal ulcerations
      observed after exposure to 16.7 Gy. GLP-2 treatment strikingly reduced the late
      radiation damage observed after 19 Gy irradiation. Microscopic observations
      revealed an improved organization of the intestinal wall and an efficient wound
      healing process, especially in the smooth muscle layers. CONCLUSION: GLP-2 has a
      clear therapeutic potential against both acute and chronic radiation enteritis.
      This therapeutic effect is mediated through an increased mucosal mass before
      tissue injury and the stimulation of still unknown mechanisms of tissue response
      to radiation damage. Although these preliminary results still need to be
      confirmed, GLP-2 might be a way to limit patient discomfort during radiotherapy
      and reduce the risk of consequential late effects.

PMID- 18035213
TI  - Dose specification and quality assurance of radiation therapy oncology group
      protocol 95-17; a cooperative group study of iridium-192 breast implants as sole
      therapy.
AB  - PURPOSE: The Radiation Therapy Oncology Group (RTOG) protocol 95-17 was a Phase
      I/II trial to evaluate multicatheter brachytherapy as the sole method of adjuvant
      breast radiotherapy for Stage I/II breast carcinoma after breast-conserving
      surgery. Low- or high-dose-rate sources were allowed. Dose prescription and
      treatment evaluation were based on recommendations in the International
      Commission on Radiation Units and Measurements (ICRU), Report 58 and included the
      parameters mean central dose (MCD), average peripheral dose, dose homogeneity
      index (DHI), and the dimensions of the low- and high-dose regions. METHODS AND
      MATERIALS: Three levels of quality assurance were implemented: (1) credentialing
      of institutions was required before entering patients into the study; (2) rapid
      review of each treatment plan was conducted before treatment; and (3)
      retrospective review was performed by the Radiological Physics Center in
      conjunction with the study chairman and RTOG dosimetry staff. RESULTS:
      Credentialing focused on the accuracy of dose calculation algorithm and
      compliance with protocol guidelines. Rapid review was designed to identify and
      correct deviations from the protocol before treatment. The retrospective review
      involved recalculation of dosimetry parameters and review of dose distributions
      to evaluate the treatment. Specifying both central and peripheral doses resulted
      in uniform dose distributions, with a mean dose homogeneity index of 0.83 +/-
      0.06. CONCLUSIONS: Vigorous quality assurance resulted in a high-quality study
      with few deviations; only 4 of 100 patients were judged as representing minor
      variations from protocol, and no patient was judged as representing major
      deviation. This study should be considered a model for quality assurance of
      future trials.

PMID- 18035214
TI  - The impact of advanced technologies on treatment deviations in radiation
      treatment delivery.
AB  - PURPOSE: To assess the impact of new technologies on deviation rates in radiation
      therapy (RT). METHODS AND MATERIALS: Treatment delivery deviations in RT were
      prospectively monitored during a time of technology upgrade. In January 2003, our
      department had three accelerators, none with "modern" technologies (e.g., without
      multileaf collimators [MLC]). In 2003 to 2004, we upgraded to five new
      accelerators, four with MLC, and associated advanced capabilities. The deviation
      rates among patients treated on "high-technology" versus "low-technology"
      machines (defined as those with vs. without MLC) were compared over time using
      the two-tailed Fisher's exact test. RESULTS: In 2003, there was no significant
      difference between the deviation rate in the "high-technology" versus "low
      technology" groups (0.16% vs. 0.11%, p = 0.45). In 2005 to 2006, the deviation
      rate for the "high-technology" groups was lower than the "low-technology" (0.083%
      vs. 0.21%, p = 0.009). This difference was caused by a decline in deviations on
      the "high-technology" machines over time (p = 0.053), as well as an unexpected
      trend toward an increase in deviations over time on the "low-technology" machines
      (p = 0.15). CONCLUSIONS: Advances in RT delivery systems appear to reduce the
      rate of treatment deviations. Deviation rates on "high-technology" machines with
      MLC decline over time, suggesting a learning curve after the introduction of new
      technologies. Associated with the adoption of "high-technology" was an unexpected
      increase in the deviation rate with "low-technology" approaches, which may
      reflect an over-reliance on tools inherent to "high-technology" machines. With
      the introduction of new technologies, continued diligence is needed to ensure
      that staff remain proficient with "low-technology" approaches.

PMID- 18035215
TI  - Cone-beam CT localization of internal target volumes for stereotactic body
      radiotherapy of lung lesions.
AB  - PURPOSE: In this study, we investigate a technique of matching internal target
      volumes (ITVs) in four-dimensional (4D) simulation computed tomography (CT) to
      the composite target volume in free-breathing on-board cone-beam (CB) CT. The
      technique is illustrated by using both phantom and patient cases. METHODS AND
      MATERIALS: A dynamic phantom with a target ball simulating respiratory motion
      with various amplitude and cycle times was used to verify localization accuracy.
      The dynamic phantom was scanned using simulation CT with a phase-based
      retrospective sorting technique. The ITV was then determined based on 10 sets of
      sorted images. The size and epicenter of the ITV identified from 4D simulation CT
      images and the composite target volume identified from on-board CBCT images were
      compared to assess localization accuracy. Similarly, for two clinical cases of
      patients with lung cancer, ITVs defined from 4D simulation CT images and CBCT
      images were compared. RESULTS: For the phantom, localization accuracy between the
      ITV in 4D simulation CT and the composite target volume in CBCT was within 1 mm,
      and ITV was within 8.7%. For patient cases, ITVs on simulation CT and CBCT were
      within 8.0%. CONCLUSION: This study shows that CBCT is a useful tool to localize
      ITV for targets affected by respiratory motion. Verification of the ITV from 4D
      simulation CT using on-board free-breathing CBCT is feasible for the target
      localization of lung tumors.

PMID- 18035216
TI  - A treatment planning analysis of inverse-planned and forward-planned intensity
      modulated radiation therapy in nasopharyngeal carcinoma.
AB  - PURPOSE: To compare dose-volume histograms of target volumes and organs at risk
      in 57 patients with nasopharyngeal carcinoma (NPC) with inverse- (IP) or forward
      planned (FP) intensity-modulated radiation treatment (IMRT). METHODS AND
      MATERIALS: The DVHs of 57 patients with NPC with IMRT with or without
      chemotherapy were reviewed. Thirty-one patients underwent IP IMRT, and 26
      patients underwent FP IMRT. Treatment goals were to prescribe a minimum dose of
      66-70 Gy for gross tumor volume and 59.4 Gy for planning target volume to greater
      than 95% of the volume. Multiple selected end points were used to compare dose
      volume histograms of the targets, including minimum, mean, and maximum doses;
      percentage of target volume receiving less than 90% (1-V90%), less than 95% (1
      V95%), and greater than 105% (1-V105%). Dose-volume histograms of organs at risk
      were evaluated with characteristic end points. RESULTS: Both planning methods
      provided excellent target coverage with no statistically significant differences
      found, although a trend was suggested in favor of improved target coverage with
      IP IMRT in patients with T3/T4 NPC (p = 0.10). Overall, IP IMRT statistically
      decreased the dose to the parotid gland, temporomandibular joint, brain stem, and
      spinal cord overall, whereas IP led to a dose decrease to the middle/inner ear in
      only the T1/T2 subgroup. CONCLUSIONS: Use of IP and FP IMRT can lead to good
      target coverage while maintaining critical structures within tolerance. The IP
      IMRT selectively spared these critical organs to a greater degree and should be
      considered the standard of treatment in patients with NPC, particularly those
      with T3/T4. The FP IMRT is an effective second option in centers with limited IP
      IMRT capacity. As a modification of conformal techniques, the human/departmental
      resources to incorporate FP-IMRT should be nominal.

PMID- 18035217
TI  - Respiratory-gated helical computed tomography of lung: reproducibility of small
      volumes in an ex vivo model.
AB  - PURPOSE: Motion-adapted radiotherapy with gated irradiation or tracking of tumor
      positions requires dedicated imaging techniques such as four-dimensional (4D)
      helical computed tomography (CT) for patient selection and treatment planning.
      The objective was to evaluate the reproducibility of spatial information for
      small objects on respiratory-gated 4D helical CT using computer-assisted
      volumetry of lung nodules in a ventilated ex vivo system. METHODS AND MATERIALS:
      Five porcine lungs were inflated inside a chest phantom and prepared with 55
      artificial nodules (mean diameter, 8.4 mm +/- 1.8). The lungs were respirated by
      a flexible diaphragm and scanned with 40-row detector CT (collimation, 24 x 1.2
      mm; pitch, 0.1; rotation time, 1 s; slice thickness, 1.5 mm; increment, 0.8 mm).
      The 4D-CT scans acquired during respiration (eight per minute) and reconstructed
      at 0-100% inspiration and equivalent static scans were scored for motion-related
      artifacts (0 or absent to 3 or relevant). The reproducibility of nodule volumetry
      (three readers) was assessed using the variation coefficient (VC). RESULTS: The
      mean volumes from the static and dynamic inspiratory scans were equal (364.9 and
      360.8 mm3, respectively, p = 0.24). The static and dynamic end-expiratory volumes
      were slightly greater (371.9 and 369.7 mm3, respectively, p = 0.019). The VC for
      volumetry (static) was 3.1%, with no significant difference between 20 apical and
      20 caudal nodules (2.6% and 3.5%, p = 0.25). In dynamic scans, the VC was greater
      (3.9%, p = 0.004; apical and caudal, 2.6% and 4.9%; p = 0.004), with a
      significant difference between static and dynamic in the 20 caudal nodules (3.5%
      and 4.9%, p = 0.015). This was consistent with greater motion-related artifacts
      and image noise at the diaphragm (p <0.05). The VC for interobserver variability
      was 0.6%. CONCLUSION: Residual motion-related artifacts had only minimal
      influence on volumetry of small solid lesions. This indicates a high
      reproducibility of spatial information for small objects in low pitch helical 4D
      CT reconstructions.

PMID- 18035219
TI  - In regards to Caudell et Al. (Int j radiat oncol biol phys 2007;65:640-645).

PMID- 18035221
TI  - In regard to Munter et Al. Changes in salivary gland function after radiotherapy
      of head and neck tumors measured by quantitative pertechnetate scintigraphy:
      comparison of intensity-modulated radiotherapy and conventional radiation therapy
      with and without amifostine. (Int j radiat oncol biol phys 2007;67:651-659).

PMID- 18035222
TI  - Efficacy of anastrozole on local recurrence in patients with favorable early
      breast cancer.

PMID- 18035224
TI  - Re-irradiation for recurrent head and neck cancer: in regard to Lee et Al. (Int j
      radiat oncol biol phys 2007;68:731-740).

PMID- 18035227
TI  - Aging-related sleep changes.
AB  - Normal aging is accompanied by changes in the sleep quality, quantity, and
      architecture. Specifically, there appears to be a measurable decrease in the
      ability of the healthy elderly to initiate and maintain sleep, accompanied by a
      decrease in the proportion of the deeper, more restorative slow-wave sleep and
      rapid eye movement sleep. There is epidemiologic evidence that this impaired
      ability to initiate, maintain, and ultimately achieve good quality, optimal sleep
      may be a marker of increased mortality and neurocognitive dysfunction. Possible
      mechanisms related to these age-related changes in sleep include age-related
      changes in circadian modulation, homeostatic factors, cardiopulmonary function,
      and endocrine function. This article describes the normal changes in sleep
      physiology in the elderly.

PMID- 18035228
TI  - Evaluation of sleep disturbances in older adults.
AB  - Older patients are at risk for a variety of sleep disorders, ranging from
      insomnia to circadian rhythm disturbances. The clinical consequence of
      unremitting sleep disturbances in the elderly population often includes
      hypersomnolence and may result in disorientation, delirium, impaired intellect,
      disturbed cognition, psychomotor retardation, or increased risk of accidents and
      injury. These symptoms may compromise overall quality of life and create social
      and economic burdens for the health care system, as well as for the caregivers.
      The clinical assessment of aging patients who have sleep complaints involves an
      in-depth multidisciplinary approach.

PMID- 18035229
TI  - The effect of chronic disorders on sleep in the elderly.
AB  - Sleep disorders are increasingly common as people age. Along with the numerous
      physiologic changes that occur with aging, sleep patterns are also altered.
      Inability to get to sleep, shorter sleep times, and changes in the normal
      circadian patterns can have an impact on an individual's overall well being. In
      addition, many common chronic conditions, such as chronic obstructive pulmonary
      disease, diabetes, dementia, chronic pain, and cancer, that are more common in
      the elderly, can also have significant effects on sleep and increase the
      prevalence of insomnia as compared with the general population. This is a result
      not only of the chronic medical illnesses themselves, but of the psychologic and
      social factors associated with the disease processes.

PMID- 18035231
TI  - Insomnia among hospitalized older persons.
AB  - Among hospitalized older persons, rates of insomnia are alarmingly high, as is
      evident by the high rates of use of sedative-hypnotic drugs, ranging from 31% to
      88%. Insomnia among hospitalized patients may represent undiagnosed sleep
      disorders, underlying medical problems, and underlying psychiatric problems.
      Causes of insomnia can be intrinsic or extrinsic. In the intensive care unit,
      which is one of the most studied areas of the hospital related to insomnia, most
      studies using polysomnography monitoring have shown that although sleep times
      seem normal (about 7&8 hours per night), no patients have normal sleep patterns.
      There is evidence supporting the use of nonpharmacologic interventions, which are
      preferable to the use of sedating drugs because of the risk associated with their
      use.

PMID- 18035230
TI  - Sleep disturbances in long-term care.
AB  - Nighttime sleep disruption is characteristic of long-term care residents, is
      typically accompanied by daytime sleepiness, and may be caused by a multitude of
      factors. Causal factors include medical and psychiatric illness, medications,
      circadian rhythm abnormalities, sleep disordered breathing and other primary
      sleep disorders, environmental factors, and lifestyle habits. There is some
      suggestion that these factors are amenable to treatment; however, further
      research on the implementation of treatments within the long-term care setting is
      needed. Additional work is also needed to understand the administrative and
      policy factors that might lead to systemic changes in how sleep is viewed and
      sleep problems are addressed in long-term care settings.

PMID- 18035232
TI  - The demented elder with insomnia.
AB  - Elders with dementia experience a high prevalence of disordered sleep that can
      present as agitation, sleep-disordered breathing, or excessive daytime napping.
      One must also consider broader contextual issues in the evaluation and treatment
      of the demented elder with insomnia, such as the caregiver and staff, as well as
      the setting in which the patient resides. The treatment approach to the demented
      elder with insomnia is difficult and largely based on clinical experience rather
      than a broad evidence base. Using a "less is better" approach in attempting
      nonpharmacologic interventions before initiating a trial of drug therapy is the
      optimal first step.

PMID- 18035233
TI  - Sleep disturbance in palliative care.
AB  - Sleep disturbance in palliative medicine is a common and challenging condition
      that significantly adds to the burden of suffering experienced by patients with
      advanced stage diseases. Sleep disorders may be primary or, more commonly, a
      secondary symptom of the advancing disease process. The diverse nature of
      patients under palliative care makes management of sleep disorders particularly
      challenging and highly individualized. Multiple pharmacologic and
      nonpharmacologic interventions have been successfully used for the management of
      sleep disturbances in palliative medicine. Yet, despite these measures, many
      patients do not seek medical attention for sleep disturbances, and health care
      providers tend to under-diagnose this condition and under-treat it when
      diagnosed, thus missing an opportunity to improve the quality of life of patients
      already suffering from the burden of terminal disease.

PMID- 18035234
TI  - Pharmacotherapy for insomnia.
AB  - Hypnotics are commonly use in the treatment of insomnia, and hypnotic use among
      older adults is more prevalent than with younger adults. Unfortunately, the use
      of hypnotics is not well studied in the ever-growing geriatric population and the
      magnitude of the medication benefit is usually not impressive. Insomnia in older
      adults is usually treated with benzodiazepines, nonbenzodiazepines, and other
      agents, such as trazodone, valerian, and melatonin. Using appropriately selected
      agents and therapy initiated with a low dose and careful monitoring of the
      patient could minimize common unwanted side effects.

PMID- 18035235
TI  - Nonpharmacologic therapy for insomnia in the elderly.
AB  - Nonpharmacologic modalities may be used alone or in combination with
      pharmacologic therapy for effective treatment of insomnia in the elderly. Nondrug
      treatments involve behavioral, cognitive, and physiologic interventions. Common
      methods of cognitive behavior therapy for insomnia include: relaxation, stimulus
      control, sleep restriction, cognitive interventions or therapy, sleep education
      and sleep hygiene, light therapy, and chronotherapy. Evidence suggests that
      nonpharmacologic treatments are effective and well suited for the clinical
      management of insomnia in the elderly.

PMID- 18035237
TI  - Light therapy for insomnia in older adults.
AB  - Exposure to bright light suppresses the production of melatonin and contributes
      to the regulation of the circadian rhythm. Because of environmental and medical
      conditions, older adults are less likely than younger adults to receive the
      prolonged, high intensity, daily bright light needed to promote a satisfactory
      sleep-wake cycle. The best available evidence for bright light therapy is in the
      management of seasonal affective disorder, which is relatively infrequent in the
      elderly population. For older adults with chronic insomnia, dementia, and
      nonseasonal depression, there is no consensus on the optimum treatment protocol
      for bright light therapy. However, in addition to sleep improvement, bright light
      therapy may be used to reduce unwanted behavioral and cognitive symptoms
      associated with dementia and depression in the elderly.

PMID- 18035238
TI  - Obstructive sleep apnea in older adults.
AB  - The "typical" presentation of obstructive sleep apnea (OSA) is chronic loud
      snoring and excessive daytime sleepiness in middle-aged obese men. OSA can result
      in increased risk for cardiovascular morbidity and mortality. The diagnostic
      features of OSA in older adults are similar to those in younger adults; however,
      the older adult may be less likely to seek medical attention or have the sleep
      disorder recognized because symptoms of snoring, sleepiness, fatigue, nocturia,
      unintentional napping, and cognitive dysfunction may be ascribed to the aging
      process itself or to other disorders. This article reviews the basic terminology
      and pathophysiology of sleep-disordered breathing, discusses why OSA may be even
      more prevalent in older adults than in the middle-aged group, and reviews
      similarities and differences between the two groups in the manifestations,
      consequences, and treatments of OSA.

PMID- 18035236
TI  - Complementary and alternative medicine for sleep disturbances in older adults.
AB  - Complementary and alternative medicines (CAM) are frequently used for the
      treatment of sleep disorders, but in many cases patients do not discuss these
      therapies directly with their health care provider. There is a growing body of
      well-designed clinical trials using CAM that have shown the following: (1)
      Melatonin is an effective agent for the treatment of circadian phase disorders
      that affect sleep; however, the role of melatonin in the treatment of primary or
      secondary insomnia is less well established. (2) Valerian has shown a benefit in
      some, but not all clinical trials. (3) Several other modalities, such as Tai Chi,
      acupuncture, acupressure, yoga, and meditation have improved sleep parameters in
      a limited number of early trials. Future work examining CAM has the potential to
      significantly add to our treatment options for sleep disorders in older adults.

PMID- 18035239
TI  - Restless legs syndrome in older adults.
AB  - Restless legs syndrome (RLS) is a common neurological disorder characterized by
      an urge to move the legs. The symptoms show a strong circadian rhythmicity, with
      onset or increase in the evening or at night; thus, sleep disturbances are the
      most frequent reason for patients seeking medical aid. The prevalence of the
      disorder increases strongly with age, with an estimated 9% to 20% of sufferers
      being among the elderly. Dopaminergic drugs are the first-line treatment option
      in RLS; opioids and anticonvulsants can also be used either as add-on or stand
      alone therapy options. Secondary forms of RLS and possible interaction with other
      medications require particular consideration in the elderly.

PMID- 18035240
TI  - Day-night differences in oxygen saturation and the frequency of desaturations in
      the first 24 hours in patients with acute stroke.
AB  - BACKGROUND: Hypoxia is common after acute stroke. Most studies of oxygenation
      after stroke were done at night. The objective of this study was to determine
      whether there are differences in oxygenation between day and night early after
      stroke. METHODS: Patients with an acute stroke were recruited within 24 hours of
      admission. Patients who were hypoxic (oxygen saturation < 90%) were excluded.
      Oxygen saturation was assessed by pulse oximetry over 24 hours. Daytime
      recordings were taken from 9 am to 9 pm and nighttime recordings from 10 pm to 6
      am. Respiratory rate and sleep/awake status were recorded twice during the day
      and the night. RESULTS: Forty patients were recruited (mean age 77 years [range
      55-93 years], 53% men; median [range] Glasgow Coma Scale score 15 [10-15] and
      Scandinavian Stroke Scale score 31 [4-56]; 80% cerebral infarcts, 20%
      hemorrhages). The median (range) respiratory rate was 20 (14-30) breaths/min in
      the day and 18 (12-32) breaths/min in the night (P < .01, Wilcoxon paired test).
      The median (range) oxygen saturation was 95.5% (87%-98.6%) in the day and 94.3%
      (80%-98%) at night (P < .001, Wilcoxon paired test). The median (range) 4% oxygen
      desaturation index was 1.7 (0.0, 18.0) in the day and 3.0 (0.0, 39.4) at night (P
      < .001, Wilcoxon paired test). Respiratory rate, oxygen saturation, and 4% oxygen
      desaturation index during the day and night were strongly correlated.
      CONCLUSIONS: All indicators of oxygenation assessed in this study were
      significantly worse at night than in the day. Because daytime and nighttime
      results were strongly correlated, borderline hypoxia during the day is strongly
      predictive of overt hypoxia at night.

PMID- 18035241
TI  - Prediction of subarachnoid hemorrhage from a ruptured cerebral aneurysm by
      discriminant analysis in women.
AB  - BACKGROUND: Using a discriminant analysis study of Japanese women, we sought to
      construct a predictive model of individuals who are at a higher risk factor of
      the occurrence of subarachnoid hemorrhage (SAH) from a ruptured cerebral
      aneurysm. METHODS: Patients consisted of a consecutive series of 124 female
      patients with first spontaneous SAH aged 30 to 79 years and aneurysm or aneurysms
      confirmed by angiography, computed tomography scan, or both at two medical
      hospitals in Nagoya, Aichi Prefecture, Japan, from April 1992 to March 1997.
      Community control subjects were identified, and matched to each patient by age
      (+/-2 years). Linear discrimination analysis was used to construct a predictive
      model to select individuals who have a higher chance of SAH. RESULTS: All of the
      5 predictor variables (lower antioxidant intake score, current smoking, family
      history of SAH, nulligravidity, and hypertension) were independently associated
      with the risk of SAH. The discriminant analysis yielded a statistically
      significant function, which explained 52% of the whole (canonical correlation
      [Rc] = 0.73; degrees of freedom [df] = 6; P = .000). This function showed that
      the rate of correct prediction was 76.2% for patients with SAH, and 82.7% for
      control subjects, and that it was able to produce an 80.4% rate of correct
      classification. CONCLUSIONS: The current study suggests that the calculated
      discriminant function, which was determined congenital (family history of SAH)
      and acquired variables simultaneously, may provide greater predictive accuracy
      for screening individuals at high risk of the occurrence of SAH in women.
      Prospective studies are needed to confirm validity and feasibility of the model
      for earlier screening for the occurrence of SAH in women.

PMID- 18035242
TI  - White matter lesions are related to impaired instrumental activities of daily
      living poststroke.
AB  - BACKGROUND: White matter lesions (WMLs) are frequent in elderly people, and have
      been associated with impaired activities of daily living (ADL) and cognitive
      decline. We sought to examine the role of WMLs and their extent, in regard to
      basic ADL, instrumental ADL (IADL), and cognitive functions, in a large well
      defined cohort examined 3 months after an ischemic stroke. METHODS: The study
      group included 395 of 486 consecutive patients aged 55 to 85 years who, 3 months
      after an ischemic stroke, completed a neuropsychological test battery and
      magnetic resonance imaging, and structured medical, neurological, and laboratory
      evaluations; assessment included an interview with a knowledgeable informant.
      RESULTS: The patients with the most severe WMLs (n = 213) were older, in
      comparison with those with moderate (n = 71) or mild/no (n = 111) WMLs. These
      patients also more often had Diagnostic and Statistical Manual of Mental
      Disorders, Third Edition dementia; had a lower Mini Mental Status score; were
      more often women; more often had impaired immediate and delayed memory
      performance, executive dysfunction, and impaired basic ADL and IADL functions;
      and had more infarcts and cortical or central atrophy in magnetic resonance
      imaging. However, there were no significant differences among the 3 groups in
      stroke severity measured on the Scandinavian Stroke Scale, in stroke-related
      depression as measured by the Beck Depression Inventory, or in stroke type.
      According to multiple logistic regression analysis, higher age (odds ratio 1.067,
      95% confidence interval 1.036-1.01) and impaired IADL (odds ratio 0.852, 95%
      confidence interval 0.778-0.931) significantly correlated with severe WMLs.
      CONCLUSIONS: Although the degree of WMLs was not associated with stroke severity,
      it was associated with global cognitive function, impaired memory functions,
      executive dysfunction, sex, and impaired basic ADL. Age and IADL functions were
      independent correlates of severe WMLs.

PMID- 18035243
TI  - Controversy of surgical treatment for severe cerebellar infarction.
AB  - Treatment for severe cerebellar infarction has been controversial. Clinical
      outcomes of patients with external ventricular drainage (EVD) and decompression
      as the first treatment for the infarction were compared. A total of 25 patients
      with severe cerebellar infarction were subdivided into two groups to compare
      outcome of the group (group A) with EVD with that of the group (group B) with
      decompressive surgery as the first surgery. There was no statistically
      significant difference in age between group A with 71 +/- 6 years and group B
      with 61 +/- 15 years. The preoperative status was Glasgow Coma Scale (GCS) score
      6 in all the patients in group A. It was GCS score 4 in one patient, GCS score 6
      in 9 patients, GCS score 7 in 8 patients, and GCS score 9 in two patients in
      group B. The preoperative neurologic background was almost the same for both
      groups. In group A, one patient had a good recovery. However, 3 patients became
      severely disabled and one patient died. In group B, 10 patients had a good
      recovery and 6 patients became moderately disabled, although two patients were
      disabled and two patients died. The outcome was good in one patient of group A
      and in 16 patients of group B, although it was poor in 4 patients each in both
      groups. Patients in group B had a significantly better prognosis than those in
      group A. No clear evidence of surgical indications for EVD or suboccipital
      decompression from neurologic signs or symptoms and from neuroimaging has been
      reported. Our results seem to suggest that pre-emptive suboccipital decompression
      with or without resection of necrosis is warranted in the patients with severe
      cerebellar infarction.

PMID- 18035244
TI  - New developments in secondary stroke prevention: impact of the
      European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) on
      clinical management.
AB  - Secondary stroke prevention is an important goal of poststroke patient treatment.
      Various pharmacologic approaches have been advocated, but the relative efficacy
      and safety of these regimens has remained the subject of much debate. Recently
      released data from the European/Australasian Stroke Prevention in Reversible
      Ischemia Trial (ESPRIT) indicated that combination therapy with aspirin and
      extended-release dipyridamole was more effective than aspirin monotherapy, and
      probably more effective than anticoagulants, for the prevention of
      cerebrovascular events after a stroke or transient ischemic attack. When viewed
      in light of results of earlier trials, these findings confirmed that combination
      aspirin plus extended-release dipyridamole therapy improved outcomes in these
      patients and is a recommended option for poststroke patient treatment.

PMID- 18035245
TI  - Case of moyamoya disease in a patient with advanced acquired immunodeficiency
      syndrome.
AB  - BACKGROUND: Moyamoya disease is an occlusion of the terminal portion of internal
      carotid arteries and proximal portion of middle and anterior cerebral arteries of
      unknown origin. Moyamoya syndrome is associated with meningitis, tuberculosis,
      syphilis, head trauma, head irradiation, brain tumor, von Recklinghausen's
      disease, tuberous sclerosis, Marfan syndrome, sickle cell anemia,
      arteriosclerosis, hypertension, and oral contraceptive use. To our knowledge,
      acquired immunodeficiency syndrome (AIDS) as a cause of moyamoya syndrome has not
      been reported in an adult population. OBJECTIVE: We report a case of moyamoya
      syndrome in a patient with AIDS and without other conditions associated with
      occlusion of the circle of Willis and formation of collateral network at the base
      of the brain and basal ganglia. METHODS: We present a case report. RESULTS: A 29
      year-old woman with an 8-year history of AIDS on multiple antiretroviral
      medications presented with recurrent tingling of the left extremities which 1
      month later progressed to mild hemiparesis and dysarthria. During the next few
      months the patient developed progressive cognitive decline and on-and-off
      fluctuations in the degree of hemiparesis. Brain magnetic resonance imaging
      showed multiple small subcortical infarct's in both parietal lobes. Magnetic
      resonance angiography showed occlusion of middle cerebral arteries distal
      internal carotid arteries, with prominent collateral network. Cerebral
      angiography confirmed moyamoya pattern. Lumbar puncture showed: white blood cell
      count 1, red blood cell count 418, protein 56, glucose 53, negative bacterial and
      acid-fast bacilli smear and culture, negative VDRL test, India ink, cryptococcal
      antigen, cytology and negative polymerase chain reaction for cytomegalovirus,
      Epstein-Barr virus, varicella-zoster virus, and herpes simplex virus type 1 and
      2. Electroencephalography showed diffuse background slowing. CONCLUSIONS: We
      hypothesize that human immunodeficiency virus (HIV) caused central nervous system
      vasculitis, which eventually led to formation of moyamoya pattern. No other
      definite causes of central nervous system vasculitis were found in our patient.
      Cerebrovascular disorders should be considered in patients with HIV/AIDS with
      focal neurologic deficit. Moyamoya syndrome as a cause of stroke should be
      considered in patients with HIV/AIDS, especially as survival improves.

PMID- 18035247
TI  - Recurrent strokes in two patients with POEMS syndrome and Castleman's disease.
AB  - POEMS syndrome is a disorder characterized by polyneuropathy, organomegaly,
      endocrinopathy, monoclonal gammopathy, and skin changes. Castleman's disease is a
      rare lymphoproliferative disorder that can be present in patients with POEMS
      syndrome. Previous case reports have documented the association between POEMS
      syndrome and arterial and venous thromboses of the coronary and lower limb
      arteries. However, only 3 patients have ever been described with POEMS syndrome,
      Castleman's disease, and stroke. Two additional patients with this combination of
      disorders are reported herein. We suspect that the strokes are a result of a
      possible intracranial vasculopathic process.

PMID- 18035246
TI  - Reperfusion seizures: a manifestation of cerebral reperfusion injury after
      administration of recombinant tissue plasminogen activator for acute ischemic
      stroke.
AB  - Reperfusion injury has been well described in medical literature; cerebral
      reperfusion injury is commonly seen in association with vascular surgical
      procedures such as carotid endarterectomies and stent placement procedures.
      Cerebral reperfusion injury can manifest as blood-brain barrier breakdown,
      cortical irritability, and epileptic seizures. Seizures induced by cerebral
      reperfusion have not been documented or reported after thrombolytic therapy for
      acute ischemic stroke. We report a patient who received intravenous recombinant
      tissue plasminogen activator within 3 hours of stroke symptom onset and developed
      the new-onset symptom of continuous, primary motor seizure activity within 20
      minutes of recombinant tissue plasminogen activator administration. These
      epileptic seizures originated in the same area as the acute brain ischemia and
      occurred during the anticipated period of cerebral reperfusion. In this article
      we describe a case report and then discuss the pathophysiology and mechanisms
      that may underlie reperfusion epileptic seizures as a manifestation of cerebral
      reperfusion injury.

PMID- 18035248
TI  - Incidental appendectomy.

PMID- 18035250
TI  - The Broad Street pump: a paradigm for policy and advocacy--a resident's lessons
      from the 2007 ACS Leadership Conference.

PMID- 18035254
TI  - Outcomes in octogenarians undergoing high-risk cancer operation: a national
      study.
AB  - BACKGROUND: Current information about outcomes in octogenarians undergoing cancer
      operations is limited largely to case series from selected centers. Population
      based data can provide more realistic estimates of the risks and benefits of
      operations in this group. STUDY DESIGN: We performed a retrospective cohort study
      of patients undergoing major resections for lung, esophageal, and pancreas
      cancer. Using the Nationwide Inpatient Sample (1994 to 2003), we examined
      operative mortality and discharge disposition in octogenarians (aged 80+ years),
      relative to younger patients (aged 65 to 69 years) (n = 272,662). We then used
      the Surveillance and End Results-Medicare-linked database (1992 to 2001) to
      measure late survival in the elderly (n = 14,088). RESULTS: Operative mortality
      among octogenarians was substantially higher than that of younger patients (aged
      65 to 69 years) for all three cancers (esophagectomy, 19.9% versus 8.8%, p <
      0.0001; pancreatectomy, 15.5% versus 6.7%, p < 0.0001; lung resection, 6.9%
      versus 3.7%, p < 0.0001). A large proportion of octogenarians were transferred to
      extended care facilities after operation, ranging from 24% after lung resection
      to 44% after esophagectomy. Five-year survival in octogenarians was low for all
      three cancers: 11% after pancreatectomy, 18% after esophagectomy and 31% after
      lung cancer resection. Survival among octogenarians with two or more
      comorbidities was worse than those with fewer comorbid diagnoses--10% versus 14%
      for pancreatectomy, 15% versus 23% for esophagectomy, and 27% versus 37% for lung
      resection. CONCLUSIONS: Population-based outcomes after high-risk cancer
      operation in octogenarians are considerably worse than typically reported in case
      series and published survival statistics. Such information might better inform
      clinical decision making in this high-risk group.

PMID- 18035255
TI  - Comparing outcomes after transthoracic and transhiatal esophagectomy: a 5-year
      prospective cohort of 17,395 patients.
AB  - BACKGROUND: Debate continues over whether transhiatal esophagectomy (THE) offers
      decreased morbidity and mortality compared with transthoracic esophagectomy
      (TTE). To definitively answer this question, we used the Nationwide Inpatient
      Sample database to compare morbidity and mortality after THE and TTE. STUDY
      DESIGN: Using ICD-9 procedure codes, we queried the Nationwide Inpatient Sample
      database for patients undergoing THE and TTE. Multivariate statistical analysis
      was completed to compare morbidity, mortality, length of stay, and hospital
      volume analysis between the groups. RESULTS: Between 1999 and 2003, 17,395
      patients included in the Nationwide Inpatient Sample underwent esophagectomy.
      Mean patient age was similar in those undergoing THE and TTE (61.9 versus 62.0
      years, respectively). Overall morbidity and mortality after esophagectomy were
      50.7% and 8.8%, respectively. In-hospital mortality after THE was 8.91% compared
      with 8.47% after TTE (p=0.642). Multivariate regression analysis showed no
      difference in the incidence of mediastinitis, wound, infectious, pulmonary,
      gastrointestinal, cardiovascular, systemic, procedure-related, or overall
      complications or hospital length of stay between the two groups. Controlling
      additionally for hospital volume showed high-volume centers (more than 10
      esophagectomies per year) had significantly lower mortality rates than low-volume
      centers (10 or fewer esophagectomies per year, p=0.024). Additionally, low-volume
      centers have a higher incidence of gastrointestinal and systemic complications in
      the TTE group (p=0.048 and p=0.038, respectively). CONCLUSIONS: This large
      volume, multicenter study constitutes the largest cohort in the literature to
      compare outcomes after THE and TTE. These findings indicate the outcomes after
      THE and TTE for esophageal disease are equivalent, although higher-volume centers
      will have lower morbidity and mortality.

PMID- 18035256
TI  - Gastrointestinal complications after coronary artery bypass grafting: a national
      study of morbidity and mortality predictors.
AB  - BACKGROUND: Previous single-institution studies have documented a 0.6% to 2.4%
      incidence of gastrointestinal (GI) complications after coronary artery bypass
      grafting (CABG), with an associated 14% to 63% mortality rate. To better
      determine the incidence and impact of GI complications after CABG, national
      outcomes for CABG were examined from 1998 to 2002. STUDY DESIGN: The Nationwide
      Inpatient Sample was queried for all patients undergoing CABG (ICD9 procedure
      codes 36.10 to 36.16). Two cohorts were compared: CABGs with and without GI
      complications. Both demographic and outcomes variables were compared by either t
      test or chi-square analysis. Logistic regression analyses indicated potential
      predictors of CABG inpatient mortality and GI complications after CABG. RESULTS:
      The incidence of GI complications among 2.7 million CABGs identified was 4.1%.
      Total hospital length of stay (19.3 versus 8.8 days) and inpatient mortality
      (12.0% versus 2.5%, both p < 0.0001) were increased in CABG patients having GI
      complications. Factors associated with increased risk of GI complications
      included: age greater than 65 years (odds ratio [OR], 2.1); hemodialysis (OR,
      3.4); intraaortic balloon pump (OR, 1.6); concomitant valve procedure (OR, 1.5);
      and procedure urgency (OR, 1.22). Use of an internal mammary graft was protective
      (OR, 0.5), but GI complications increased inpatient mortality risk (OR, 2.6).
      CONCLUSIONS: This national population-based study indicates that GI complications
      after CABG occur at a higher rate than previously described, leading to increased
      hospital length of stay and mortality.

PMID- 18035258
TI  - Impact of parenteral nutrition-associated liver disease on intestinal transplant
      waitlist dynamics.
AB  - BACKGROUND: United Network for Organ Sharing (UNOS) reports indicate that waiting
      list mortality for intestinal transplant candidates greatly exceeds that for all
      other organ transplant candidates. But United Network for Organ Sharing outcomes
      reports have not routinely distinguished between the intestine candidate
      subgroups that are listed only for an intestine and those that are also listed
      for a liver. STUDY DESIGN: Data were obtained by request from the collaborative
      Organ Procurement and Transplantation Network (United Network for Organ
      Sharing)/Scientific Registry of Transplant Recipients (University Research and
      Education Association) database. Waiting list data for intestinal transplant
      recipients from 1995 to 2004 were divided into those candidates listed for only
      an intestine and those listed for both an intestine and a liver. Additional data
      concerning overall waiting list outcomes and posttransplant survival rates
      stratified into pediatric and adult subsets were also obtained and analyzed.
      RESULTS: The overall number of candidates on the intestinal transplant waiting
      list has increased steadily since 1995 and, consistently, the majority of
      candidates have also been listed for a liver. This subset was found to have both
      a higher relative risk of dying while awaiting transplantation and lower relative
      odds of receiving transplants. In addition, parenteral nutrition-associated liver
      disease is a major problem across all age groups, as evidenced by the combined
      liver and intestine listings that compose the majority of both adult and
      pediatric waiting list populations. Posttransplant survival data were found to be
      superior for isolated intestine recipients compared with liver-intestine
      recipients. CONCLUSIONS: The preponderance of dual listings and their associated
      inferior outcomes, before and after transplantation, has skewed overall
      intestinal transplant outcomes. Because progression of parenteral nutrition
      associated liver disease can be insidious, and recognition of irreversibility is
      often difficult, intestine-only transplants should be considered early for high
      risk patients before parenteral nutrition-associated liver disease progression
      mandates inclusion of a liver graft also.

PMID- 18035257
TI  - Early prediction of hypocalcemia after thyroidectomy using parathyroid hormone:
      an analysis of pooled individual patient data from nine observational studies.
AB  - BACKGROUND: Monitoring for hypocalcemia after thyroidectomy, using only symptoms
      and serum calcium levels, can delay the discharge of patients who will remain
      normocalcemic and can delay the treatment of hypocalcemic patients. STUDY DESIGN:
      We conducted a systematic search for articles describing use of parathyroid
      hormone (PTH) assay, checked within hours of completing thyroidectomy, to predict
      postoperative symptomatic hypocalcemia. Studies were excluded if all patients
      were treated with postoperative calcium, or if early PTH values were used to
      alter management of the patient. Individual patient data (perioperative PTH and
      calcium levels, development of hypocalcemia) were obtained for 457 patients from
      the corresponding authors of 9 studies and pooled to yield the following results.
      RESULTS: PTH, checked at three time periods after removal of the thyroid gland (0
      to 20 minutes, 1 to 2 hours, and 6 hours), was substantially lower in patients
      who became hypocalcemic compared with those who remained normocalcemic. The
      accuracy of PTH in determining hypocalcemia increased with time and was excellent
      when checked 1 to 6 hours postoperatively. A single PTH threshold (65% decrease
      compared with preoperative level), checked 6 hours after completing
      thyroidectomy, had a sensitivity of 96.4% and specificity of 91.4% in detecting
      postoperative hypocalcemia. CONCLUSIONS: PTH assay, when checked 1 to 6 hours
      after thyroidectomy, has excellent accuracy in determining which patients will
      become symptomatically hypocalcemic. Routine use of this assay should be
      considered because it may allow earlier discharge of the normocalcemic patient
      and earlier identification of patients requiring treatment of postthyroidectomy
      hypocalcemia.

PMID- 18035259
TI  - Early cholecystectomy for mild to moderate gallstone pancreatitis shortens
      hospital stay.
AB  - BACKGROUND: The timing of cholecystectomy in gallstone pancreatitis remains
      controversial. We hypothesized that in patients with mild to moderate gallstone
      pancreatitis (three or fewer Ranson's criteria), performing early cholecystectomy
      before resolution of laboratory or physical examination abnormalities would
      result in shorter hospitalization, without adversely affecting outcomes. STUDY
      DESIGN: An observational study consisting of a retrospective and a prospective
      group was conducted. For the prospective group, a deliberate policy of early
      cholecystectomy (less than 48 hours from admission) was used. The primary end
      point was total length of hospital stay. Secondary endpoints were time from
      admission to definitive operation, need for endoscopic retrograde
      cholangiography, and major complications (organ failure and death). RESULTS:
      Group I consisted of 177 patients retrospectively reviewed, and Group II was
      composed of 43 patients prospectively followed. There were no differences between
      the two groups with respect to demographics. With respect to admission laboratory
      values, there was a significant difference in median serum amylase, but there
      were no differences in median serum levels of lipase, total bilirubin, albumin,
      white blood cell count, or Ranson's score. The median length of hospital stay was
      7 days in Group I versus 4 days in Group II (p=or< 0.001). Median time from
      admission to cholecystectomy was 5 days in Group I versus 2 days in Group II
      (p=or< 0.0001). Complication rates were similar and there were no deaths in
      either group. CONCLUSIONS: In patients with mild to moderate gallstone
      pancreatitis, a policy of early cholecystectomy resulted in a significantly
      reduced length of hospital stay with no increase in complications or mortality.

PMID- 18035260
TI  - Comparison of mortality risk adjustment using a clinical data algorithm (American
      College of Surgeons National Surgical Quality Improvement Program) and an
      administrative data algorithm (Solucient) at the case level within a single
      institution.
AB  - BACKGROUND: There is great interest in efficiently evaluating health care
      quality, but there is controversy over the use of administrative versus clinical
      data methods. We sought to compare actual mortality with risk-adjusted expected
      mortality in a sample population calculated by two different methods; one based
      on preexisting administrative records and one based on chart reviews. STUDY
      DESIGN: We examined a sample of patients (n = 1,234) undergoing surgical
      procedures at an academic teaching hospital during 1 year. The first risk
      adjustment method was that used by the National Surgical Quality Improvement
      Program, which is based on dedicated medical record review. The second method was
      that used by Solucient, LLC, which is based on preexisting administrative
      records. RESULTS: The ratio of observed to expected mortality for this population
      set was higher using the National Surgical Quality Improvement Program algorithm
      (1.1; 95% CI, 0.8 to 1.5) than using the Solucient algorithm (0.9; 95% CI, 0.6 to
      1.2) but neither estimate was notably different from 1.0. Similarly, when
      observed to expected mortality ratios were calculated separately for each
      quartile of mortality, there were no marked differences within quartiles,
      although minor differences with potential importance were noted. Fit was
      comparable by age categories, gender, and American Society of Anesthesiologists'
      categories. A number of actual deaths had higher predicted mortality scores using
      the Solucient algorithm. CONCLUSIONS: Risk-adjusted mortality estimates were
      comparable using administrative or clinical data. Minor performance differences
      might still have implications. Because of the potential lower cost of using
      administrative data, this type of algorithm can be an efficient alternative and
      should continue to be investigated.

PMID- 18035261
TI  - Risk-adjusted morbidity in teaching hospitals correlates with reported levels of
      communication and collaboration on surgical teams but not with scale measures of
      teamwork climate, safety climate, or working conditions.
AB  - BACKGROUND: Since the Institute of Medicine patient safety reports, a number of
      survey-based measures of organizational climate safety factors (OCSFs) have been
      developed. The goal of this study was to measure the impact of OCSFs on risk
      adjusted surgical morbidity and mortality. STUDY DESIGN: Surveys were
      administered to staff on general/vascular surgery services during a year. Surveys
      included multiitem scales measuring OCSFs. Additionally, perceived levels of
      communication and collaboration with coworkers were assessed. The National
      Surgical Quality Improvement Program was used to assess risk-adjusted morbidity
      and mortality. Correlations between outcomes and OCSFs were calculated and
      between outcomes and communication/collaboration with attending and resident
      doctors, nurses, and other providers. RESULTS: Fifty-two sites participated in
      the survey: 44 Veterans Affairs and 8 academic medical centers. A total of 6,083
      surveys were returned, for a response rate of 52%. The OCSF measures of teamwork
      climate, safety climate, working conditions, recognition of stress effects, job
      satisfaction, and burnout demonstrated internal validity but did not correlate
      with risk-adjusted outcomes. Reported levels of communication/collaboration with
      attending and resident doctors correlated with risk-adjusted morbidity.
      CONCLUSIONS: Survey-based teamwork, safety climate, and working conditions scales
      are not confirmed to measure organizational factors that influence risk-adjusted
      surgical outcomes. Reported communication/collaboration with attending and
      resident doctors on surgical services influenced patient morbidity. This suggests
      the importance of doctors' coordination and decision-making roles on surgical
      teams in providing high-quality and safe care. We propose risk-adjusted morbidity
      as an effective measure of surgical patient safety.

PMID- 18035262
TI  - Anastomotic leakage after elective right versus left colectomy for cancer:
      prevalence and independent risk factors.
AB  - BACKGROUND: Anastomotic leakage in colorectal surgery remains a major challenge
      because of its early and late consequences. STUDY DESIGN: To determine whether
      prevalence and risk factors for anastomotic leakage (AL) differed between right
      and left elective colectomy for cancer, we conducted univariate and multivariate
      analyses and compared 33 variables (15 preoperative, 18 intraoperative) culled
      prospectively for 520 right and 1,230 left colectomies, followed by immediate
      anastomosis in 1,750 adult patients with or without AL. RESULTS: The overall AL
      rate was 4% (71 of 1,750) and was significantly lower (p < 0.0001) for right (7
      of 520=1.35%) than for left colectomy (64 of 1,230=5.20%). Overall mortality was
      4.1% (68 of 1,750), and was not statistically different (p=0.50) between right
      (4.6%, 24 of 520) and left (3.6%, 44 of 1,230)) colectomy. In right colectomy,
      differences in associated mortality rates with (14.3%, 1 of 7) and without (4.5%,
      23 of 513) AL were not statistically significant (p=0.28), but in left colectomy,
      associated mortality was statistically significantly higher (p < 0.006) with AL
      (10.9%, 7 of 64) than without it (3.2%, 37 of 1,166). Independent risk factors
      for AL were preoperative in right colectomy: loss of weight (> 10%), odds ratio
      (OR)=5.62, with 95% CI 1.06 to 29.8; and intraoperative in left colectomy:
      palliative resection (OR=2.12; 95% CI 1.06 to 4.23), "poor" colonic cleanliness
      (OR=2.4; 95% CI 1.34 to 4.28), proximal colorectal anastomosis (OR=1.34; 95% CI 1
      to 1.8), and distal colorectal anastomosis (OR=3.91; 95% CI 1.64 to 9.81).
      CONCLUSIONS: In right colectomy for cancer, preoperative nutritive support
      leading to regain of lost weight could reduce postoperative morbidity. Concerning
      left colectomy, if colonic cleanliness is poor, intraoperative colonic lavage
      should be done. When poor colonic cleanliness is associated with palliative
      resection and low distal rectal anastomosis, a protective stoma should be
      considered.

PMID- 18035263
TI  - Pedestrians injured by automobiles: risk factors for cervical spine injuries.
AB  - BACKGROUND: Diagnosis of cervical spine injuries (CSI) in multitrauma patients,
      especially in the presence of head trauma, can be difficult. Identification of
      risk factors associated with CSI can help avoid missed or delayed diagnosis.
      METHODS: Trauma registry study of pedestrian injuries caused by being hit by an
      automobile. Data abstracted for each patient included age, gender, Glasgow Coma
      Score on admission, Injury Severity Score, Abbreviated Injury Scale (AIS) for
      each body area, level of cervical spine injuries, and associated injuries. The
      incidence of spine injuries was derived for 4 age groups (14 years and younger,
      15 to 55 years, 56 to 65 years, and older than 65 years). Logistic regression
      analysis was performed to identify risk factors associated with CSI. RESULTS:
      There were 8,401 pedestrian injuries caused by automobiles, and 178 patients
      (2.1%) had CSI. Incidence of CSI increased with age (0.3% in the age group 14
      years and younger, 2.2% in the group 15 to 55 years, 3.7% in the group 56 to 65
      years, and 4.4% in the group older than 65 years). Using the youngest age group
      (14 years and younger) as reference, relative risk of CSI in the other groups was
      7.0, 12.1, and 14.2, respectively (p < 0.0001). Patients with severe head trauma
      (AIS > 3) were significantly more likely to have CSI than patients with less
      severe head injuries (AIS <or= 3) (1.3% versus 9.0%, p < 0.0001). In the group of
      5,040 injuries with no head trauma, there was not even a single case of CSI.
      Stepwise logistic regression analysis identified age, severe head injury (AIS >
      3), severe chest trauma (AIS > 3), pelvic fracture, and femur fracture as
      independent risk factors for CSI. CONCLUSIONS: Incidence of CSI after injuries to
      pedestrians hit by automobiles increases with age and severity of head trauma.
      Age, severe head trauma, severe chest trauma, pelvic fracture, and femur
      fractures are independent predictors of CSI.

PMID- 18035264
TI  - Omental transposition in treatment of Alzheimer disease.

PMID- 18035265
TI  - Light and dark: surgeons, radiologists, and why they need mutual understanding to
      succeed.

PMID- 18035266
TI  - Communication pitfalls with cancer patients: "hit-and-run" deliveries of bad
      news.

PMID- 18035267
TI  - Acute airway compression with achalasia.

PMID- 18035268
TI  - Cholelithiasis and cholecystitis in a retained gallbladder remnant after
      cholecystectomy.

PMID- 18035269
TI  - Clinical usefulness of biliary scope for Pringle's maneuver in laparoscopic
      hepatectomy.

PMID- 18035270
TI  - The two-pound rule: a personal experience with 1,226 cases of esophageal
      dilation.

PMID- 18035272
TI  - Happy anniversary.

PMID- 18035273
TI  - Development of public resources to support quantitative imaging methods in
      cancer.

PMID- 18035274
TI  - Noninvasive differentiation of uric acid versus non-uric acid kidney stones using
      dual-energy CT.
AB  - RATIONALE AND OBJECTIVES: To determine the accuracy and sensitivity for dual
      energy computed tomography (DECT) discrimination of uric acid (UA) stones from
      other (non-UA) renal stones in a commercially implemented product. MATERIALS AND
      METHODS: Forty human renal stones comprising uric acid (n=16), hydroxyapatite
      (n=8), calcium oxalate (n=8), and cystine (n=8) were inserted in four porcine
      kidneys (10 each) and placed inside a 32-cm water tank anterior to a cadaver
      spine. Spiral dual-energy scans were obtained on a dual-source, 64-slice computed
      tomography (CT) system using a clinical protocol and automatic exposure control.
      Scanning was performed at two different collimations (0.6 mm and 1.2 mm) and
      within three phantom sizes (medium, large, and extra large) resulting in a total
      of six image datasets. These datasets were analyzed using the dual-energy
      software tool available on the CT system for both accuracy (number of stones
      correctly classified as either UA or non-UA) and sensitivity (for UA stones).
      Stone characterization was correlated with micro-CT. RESULTS: For the medium and
      large phantom sizes, the DECT technique demonstrated 100% accuracy (40/40),
      regardless of collimation. For the extra large phantom size and the 0.6-mm
      collimation (resulting in the noisiest dataset), three (two cystine and one small
      UA) stones could not be classified (93% accuracy and 94% sensitivity). For the
      extra large phantom size and the 1.2-mm collimation, the dual-energy tool failed
      to identify two small UA stones (95% accuracy and 88% sensitivity). CONCLUSIONS:
      In an anthropomorphic phantom model, dual-energy CT can accurately discriminate
      uric acid stones from other stone types.

PMID- 18035275
TI  - The Lung Image Database Consortium (LIDC): ensuring the integrity of expert
      defined "truth".
AB  - RATIONALE AND OBJECTIVES: Computer-aided diagnostic (CAD) systems fundamentally
      require the opinions of expert human observers to establish "truth" for algorithm
      development, training, and testing. The integrity of this "truth," however, must
      be established before investigators commit to this "gold standard" as the basis
      for their research. The purpose of this study was to develop a quality assurance
      (QA) model as an integral component of the "truth" collection process concerning
      the location and spatial extent of lung nodules observed on computed tomography
      (CT) scans to be included in the Lung Image Database Consortium (LIDC) public
      database. MATERIALS AND METHODS: One hundred CT scans were interpreted by four
      radiologists through a two-phase process. For the first of these reads (the
      "blinded read phase"), radiologists independently identified and annotated
      lesions, assigning each to one of three categories: "nodule >or=3 mm," "nodule <3
      mm," or "non-nodule >or=3 mm." For the second read (the "unblinded read phase"),
      the same radiologists independently evaluated the same CT scans, but with all of
      the annotations from the previously performed blinded reads presented; each
      radiologist could add to, edit, or delete their own marks; change the lesion
      category of their own marks; or leave their marks unchanged. The post-unblinded
      read set of marks was grouped into discrete nodules and subjected to the QA
      process, which consisted of identification of potential errors introduced during
      the complete image annotation process and correction of those errors. Seven
      categories of potential error were defined; any nodule with a mark that satisfied
      the criterion for one of these categories was referred to the radiologist who
      assigned that mark for either correction or confirmation that the mark was
      intentional. RESULTS: A total of 105 QA issues were identified across 45 (45.0%)
      of the 100 CT scans. Radiologist review resulted in modifications to 101 (96.2%)
      of these potential errors. Twenty-one lesions erroneously marked as lung nodules
      after the unblinded reads had this designation removed through the QA process.
      CONCLUSIONS: The establishment of "truth" must incorporate a QA process to
      guarantee the integrity of the datasets that will provide the basis for the
      development, training, and testing of CAD systems.

PMID- 18035276
TI  - The Lung Image Database Consortium (LIDC) data collection process for nodule
      detection and annotation.
AB  - RATIONALE AND OBJECTIVES: The Lung Image Database Consortium (LIDC) is developing
      a publicly available database of thoracic computed tomography (CT) scans as a
      medical imaging research resource to promote the development of computer-aided
      detection or characterization of pulmonary nodules. To obtain the best estimate
      of the location and spatial extent of lung nodules, expert thoracic radiologists
      reviewed and annotated each scan. Because a consensus panel approach was neither
      feasible nor desirable, a unique two-phase, multicenter data collection process
      was developed to allow multiple radiologists at different centers to
      asynchronously review and annotate each CT scan. This data collection process was
      also intended to capture the variability among readers. MATERIALS AND METHODS:
      Four radiologists reviewed each scan using the following process. In the first or
      "blinded" phase, each radiologist reviewed the CT scan independently. In the
      second or "unblinded" review phase, results from all four blinded reviews were
      compiled and presented to each radiologist for a second review, allowing the
      radiologists to review their own annotations together with the annotations of the
      other radiologists. The results of each radiologist's unblinded review were
      compiled to form the final unblinded review. An XML-based message system was
      developed to communicate the results of each reading. RESULTS: This two-phase
      data collection process was designed, tested, and implemented across the LIDC.
      More than 500 CT scans have been read and annotated using this method by four
      expert readers; these scans either are currently publicly available at
      http://ncia.nci.nih.gov or will be in the near future. CONCLUSIONS: A unique data
      collection process was developed, tested, and implemented that allowed multiple
      readers at distributed sites to asynchronously review CT scans multiple times.
      This process captured the opinions of each reader regarding the location and
      spatial extent of lung nodules.

PMID- 18035278
TI  - Semiautomatic mammographic parenchymal patterns classification using multiple
      statistical features.
AB  - RATIONALE AND OBJECTIVES: Our project was to investigate a complete methodology
      for the semiautomatic assessment of digital mammograms according to their
      density, an indicator known to be correlated to breast cancer risk. The BI-RADS
      four-grade density scale is usually employed by radiologists for reporting breast
      density, but it allows for a certain degree of subjective input, and an objective
      qualification of density has therefore often been reported hard to assess. The
      goal of this study was to design an objective technique for determining breast BI
      RADS density. MATERIALS AND METHODS: The proposed semiautomatic method makes use
      of complementary pattern recognition techniques to describe manually selected
      regions of interest (ROIs) in the breast with 36 statistical features. Three
      different classifiers based on a linear discriminant analysis or Bayesian
      theories were designed and tested on a database consisting of 1408 ROIs from 88
      patients, using a leave-one-ROI-out technique. Classifications in optimal feature
      subspaces with lower dimensionality and reduction to a two-class problem were
      studied as well. RESULTS: Comparison with a reference established by the
      classifications of three radiologists shows excellent performance of the
      classifiers, even though extremely dense breasts continue to remain more
      difficult to classify accurately. For the two best classifiers, the exact
      agreement percentages are 76% and above, and weighted kappa values are 0.78 and
      0.83. Furthermore, classification in lower dimensional spaces and two-class
      problems give excellent results. CONCLUSION: The proposed semiautomatic
      classifiers method provides an objective and reproducible method for
      characterizing breast density, especially for the two-class case. It represents a
      simple and valuable tool that could be used in screening programs, training,
      education, or for optimizing image processing in diagnostic tasks.

PMID- 18035277
TI  - The Lung Image Database Consortium (LIDC): a comparison of different size metrics
      for pulmonary nodule measurements.
AB  - RATIONALE AND OBJECTIVES: The goal was to investigate the effects of choosing
      between different metrics in estimating the size of pulmonary nodules as a factor
      both of nodule characterization and of performance of computer aided detection
      systems, because the latter are always qualified with respect to a given size
      range of nodules. MATERIALS AND METHODS: This study used 265 whole-lung CT scans
      documented by the Lung Image Database Consortium (LIDC) using their protocol for
      nodule evaluation. Each inspected lesion was reviewed independently by four
      experienced radiologists who provided boundary markings for nodules larger than 3
      mm. Four size metrics, based on the boundary markings, were considered: a
      unidimensional and two bidimensional measures on a single image slice and a
      volumetric measurement based on all the image slices. The radiologist boundaries
      were processed and those with four markings were analyzed to characterize the
      interradiologist variation, while those with at least one marking were used to
      examine the difference between the metrics. RESULTS: The processing of the
      annotations found 127 nodules marked by all of the four radiologists and an
      extended set of 518 nodules each having at least one observation with three
      dimensional sizes ranging from 2.03 to 29.4 mm (average 7.05 mm, median 5.71 mm).
      A very high interobserver variation was observed for all these metrics: 95% of
      estimated standard deviations were in the following ranges for the three
      dimensional, unidimensional, and two bidimensional size metrics, respectively (in
      mm): 0.49-1.25, 0.67-2.55, 0.78-2.11, and 0.96-2.69. Also, a very large
      difference among the metrics was observed: 0.95 probability-coverage region
      widths for the volume estimation conditional on unidimensional, and the two
      bidimensional size measurements of 10 mm were 7.32, 7.72, and 6.29 mm,
      respectively. CONCLUSIONS: The selection of data subsets for performance
      evaluation is highly impacted by the size metric choice. The LIDC plans to
      include a single size measure for each nodule in its database. This metric is not
      intended as a gold standard for nodule size; rather, it is intended to facilitate
      the selection of unique repeatable size limited nodule subsets.

PMID- 18035279
TI  - Phase-sensitive inversion recovery single-shot balanced steady-state free
      precession for detection of myocardial infarction during a single breathhold.
AB  - RATIONALE AND OBJECTIVES: We sought to show that phase-sensitive detection and a
      single-shot technique allow imaging of the heart for detection of myocardial
      infarction during a single breathhold without adaptation of the inversion time.
      MATERIALS AND METHODS: Thirty-five patients at 2 weeks to 3 months after Q-wave
      myocardial infarction were examined on a 1.5-T MR system 10 minutes after the
      administration of a double-dose extravascular contrast agent. In order to
      determine the optimal inversion recovery time (TI), a TI scout sequence was
      performed. An IR-turboFlash sequence with optimized TI was used as standard of
      reference. A phase-sensitive inversion recovery (PSIR) single-shot TrueFISP
      sequence, which allows imaging of nine slices during one breathhold (TR/TE/FA/BW:
      2.2 ms/1.1 ms/60 degrees , 8 degrees /1220 Hz/Px) was used with a nominal TI of
      200 ms. Spatial resolution was identical for both techniques: 1.3 mm x 1.8 mm x 8
      mm. Infarct volumes, area of infarction on a selected slice, and scan time for
      imaging delayed contrast enhancement (DCE) were compared. RESULTS: The mean
      values for the time of imaging DCE were 10 minutes 43 seconds for the IR
      turboFLASH and 17 seconds (P<.001) for the PSIR single-shot TrueFISP sequence. No
      significant difference was found for the mean values of the infarct volumes with
      18.7 ml (IR turboFLASH) and 17.3 ml (PSIR single-shot TrueFISP). The values for
      the correlation coefficients of the infarct volumes and infarct areas of the two
      different techniques were r=0.95 (P<.004) and r=0.97 (P<.002). The regression
      equations were y=0.76+0.92*x and y=0.07+0.93*x, respectively. CONCLUSIONS: PSIR
      single-shot TrueFISP allows for accurate identification of myocardial infarction
      during a single breathhold with reduction of scan time by a factor of 38.

PMID- 18035280
TI  - Three-dimensional isotropic wavelets for post-acquisitional extraction of latent
      images of atherosclerotic plaque components from micro-computed tomography of
      human coronary arteries.
AB  - RATIONALE AND OBJECTIVES: The capability of wavelet transforms to separate
      signals into frequency bands is the basis for its use in image compression and
      storage, data management and transmission, and, recently, extraction of latent
      images of tissue components from noisy medical images. Analysis of temporal
      variations of radiofrequency backscatter of intravascular ultrasound with one
      dimensional wavelets can detect lipid-laden plaque in coronary arteries with a
      sensitivity and specificity of >80%. In this study we evaluate the capability of
      a novel, 3-dimensional isotropic wavelet analysis to perform high resolution, non
      directionally biased, statistically reliable, non-invasive discrimination between
      components of human coronary atherosclerotic plaques in micro-CT. MATERIALS AND
      METHODS: Coronary artery segments (5-15 mm) were excised at necropsy from 18
      individuals with advanced coronary atherosclerosis. Specimens were imaged using a
      GE Locus SP ex vivo micro-CT scanner and processed for histological correlation
      (833 sections). The isotropic wavelet constructs were applied to the entire
      volume of CT data of each arterial segment to distinguish tissue textures of
      varying scales and intensities. Voxels were classified and plaque
      characterization achieved by comparing the relative magnitudes of these wavelet
      constituents to that of several reference plaque tissue components. RESULTS:
      Processing of micro-CT images via these isotropic wavelet algorithms permitted 3
      D, color-coded, high resolution, digital discrimination between lumen, calcific
      deposits, lipid-rich deposits, and fibromuscular tissue providing detail not
      possible with conventional thresholding based on Hounsfield intensity units.
      Using the isotropic wavelets (with histology as the gold standard), lipid-rich
      pools approaching the size of the filter for the isotropic wavelet algorithm
      (0.25 mm [250 microns] in length) were identified with 81% sensitivity and 86%
      specificity. Calcific deposits, fibromuscular tissue, and lumen equal to or
      larger than the wavelet filter size were detected without error (100% sensitivity
      and specificity). CONCLUSION: Isotropic wavelet analysis permits high resolution,
      multi-dimensional identification of coronary atherosclerotic plaque components in
      micro-CT with sensitivity and specificity similar to that achieved with data
      obtained invasively (from IVUS in vivo) using one-dimensional wavelets. Further
      studies are necessary to test the applicability of this technology to clinical,
      multi-detector scanners.

PMID- 18035281
TI  - Hepatic enhancement in colorectal cancer: texture analysis correlates with
      hepatic hemodynamics and patient survival.
AB  - RATIONALE AND OBJECTIVES: Perfusion imaging of the liver has attracted interest
      as a potential means for earlier detection of hepatic metastases, but the
      techniques are complex and do not form part of routine imaging protocols. This
      study assesses whether the hemodynamic status of the liver of patients with
      colorectal cancer but apparently normal hepatic morphology is reflected by
      texture features within a single portal-phase contrast enhanced computed
      tomography (CT) image and correlates texture with overall survival. MATERIALS AND
      METHODS: Portal-phase CT images from 27 patients with colorectal cancer but no
      apparent hepatic metastases were processed using a band-pass filter that
      highlighted image features at different spatial frequencies. A range of
      parameters reflecting liver texture on filtered images were correlated against CT
      hepatic perfusion index (HPI) and patient survival. RESULTS: After image
      filtration, entropy values from hepatic regions were inversely correlated with
      HPI (r=-0.503978, P=.007355), and directly correlated with survival (r=0.489642,
      P=.009533). An entropy value below 2.0 identified four patients who died within
      36 months of their CT scan with sensitivity 100% and specificity 65% (P<.03).
      CONCLUSION: The hemodynamic status of the liver is reflected by subtle changes in
      coarse texture on portal phase images that can be revealed by texture analysis.
      Texture analysis has the potential to identify colorectal cancer patients with an
      apparently normal portal phase hepatic CT but reduced survival.

PMID- 18035283
TI  - Four-dimensional vascular tree reconstruction using moving grid deformation.
AB  - RATIONALE AND OBJECTIVES: Thinned perforator flaps have been widely used in
      plastic surgery for greater survivability and decreased morbidity. However,
      quantitative analysis of three-dimensional (3D) blood flow direction and location
      has not been examined yet. Such information will benefit and guide the surgical
      thinning and dissection process. Toward this goal, this study was performed for
      3D vascular tree reconstruction with the incorporation of temporal contrast-agent
      propagation information (three spatial dimensions plus one temporal dimension;
      ie, 4D). MATERIALS AND METHODS: A novel computational framework by adopting a
      moving grid deformation method is presented. To take advantage of temporal
      information of the bolus propagating, a sequential segmentation procedure is
      proposed. Moreover, the temporal evolution of the vascular tree (4D vascular
      tree) is reconstructed during the procedure. RESULTS: Eight anterolateral thigh
      perforator flaps from eight cadavers were used for this study. The age range is
      60-80 years old and the gender includes four males and four females. The 3D
      nature of the vascular structure and 4D vascular tree evolving process are showed
      in comparison with maximum intensity projection images. CONCLUSION: The proposed
      computational framework demonstrates effectiveness in the modeling of 4D vascular
      tree. Furthermore, it reveals the ability to detect small vessel tree structures
      that are beyond the limit of image resolution.

PMID- 18035282
TI  - In vivo monitoring response to chemotherapy of human diffuse large B-cell
      lymphoma xenografts in SCID mice by 1H and 31P MRS.
AB  - RATIONALE AND OBJECTIVES: A reliable noninvasive method for in vivo detection of
      early therapeutic response of non-Hodgkin's lymphoma (NHL) patients would be of
      great clinical value. This study evaluates the feasibility of (1)H and (31)P
      magnetic resonance spectroscopy (MRS) for in vivo detection of response to
      combination chemotherapy of human diffuse large B-cell lymphoma (DLCL2)
      xenografts in severe combined immunodeficient (SCID) mice. MATERIALS AND METHODS:
      Combination chemotherapy with cyclophosphamide, hydroxy doxorubicin, Oncovin,
      prednisone, and bryostatin 1 (CHOPB) was administered to tumor-bearing SCID mice
      weekly for up to four cycles. Spectroscopic studies were performed before the
      initiation of treatment and after each cycle of the CHOPB. Proton MRS for
      detection of lactate and total choline was performed using a selective multiple
      quantum-coherence-transfer (Sel-MQC) and a spin-echo-enhanced Sel-MQC (SEE-Sel
      MQC) pulse sequence, respectively. Phosphorus-31 MRS using a nonlocalized, single
      pulse sequence without proton decoupling was also performed on these animals.
      RESULTS: Significant decreases in lactate and total choline were detected in the
      DLCL2 tumors after one cycle of CHOPB chemotherapy. The ratio of
      phosphomonoesters to beta-nucleoside triphosphate (PME/betaNTP, measured by (31)P
      MRS) significantly decreased in the CHOPB-treated tumors after two cycles of
      CHOPB. The control tumors did not exhibit any significant changes in either of
      these metabolites. CONCLUSIONS: This study demonstrates that (1)H and (31)P MRS
      can detect in vivo therapeutic response of NHL tumors and that lactate and
      choline offer a number of advantages over PMEs as markers of early therapeutic
      response.

PMID- 18035284
TI  - Computer-aided diagnosis scheme for detection of lacunar infarcts on MR images.
AB  - RATIONALE AND OBJECTIVES: The detection and management of asymptomatic lacunar
      infarcts on magnetic resonance (MR) images are important tasks for radiologists
      to ensure the prevention of severe cerebral infarctions. However, accurate
      identification of the lacunar infarcts on MR images is a difficult task for the
      radiologists. Therefore the purpose of this study was to develop a computer-aided
      diagnosis scheme for the detection of lacunar infarcts to assist radiologists'
      interpretation as a "second opinion." MATERIALS AND METHODS: Our database
      comprised 1,143 T1- and 1,143 T2-weighted images obtained from 132 patients. The
      locations of the lacunar infarcts were determined by experienced
      neuroradiologists. We first segmented the cerebral region in a T1-weighted image
      by using a region growing technique for restricting the search area of lacunar
      infarcts. For identifying the initial lacunar infarcts candidates, a top-hat
      transform and multiple-phase binarization were then applied to the T2-weighted
      image within the segmented cerebral region. For eliminating the false positives
      (FPs), we determined 12 features--the locations x and y, signal intensity
      differences in the T1- and T2-weighted images, nodular components from a scale of
      1 to 4, and nodular and linear components from a scale of 1 to 4. The nodular
      components and the linear components were obtained using a filter bank technique.
      The rule-based schemes and a support vector machine with 12 features were applied
      to the regions of the initial candidates for distinguishing between lacunar
      infarcts and FPs. RESULTS: Our computerized scheme was evaluated by using a
      holdout method. The sensitivity of the detection of lacunar infarcts was 96.8%
      (90/93) with 0.76 FP per image. CONCLUSIONS: Our computerized scheme would be
      useful in assisting radiologists for identifying lacunar infarcts in MR images.

PMID- 18035285
TI  - Nonrigid registration for subtraction CT angiography applied to the carotids and
      cranial arteries.
AB  - RATIONALE AND OBJECTIVES: Computed tomography angiography (CTA) is an established
      tool for vascular imaging. However, high-intensity nonvascular structures in the
      contrast image can seriously hamper luminal visualization. This is an issue for
      three-dimensional visualization, where high-intensity structures might cover the
      underlying vasculature. But also in two dimensions, calcified plaques adjacent to
      the contrast-enhanced vessel lumen impede correct determination of the vessel
      boundary. High-intensity structures can be eliminated using subtraction CTA,
      where a native image is subtracted from the contrast image. However, patient and
      organ motion limits the widespread application of this technique. We propose to
      use nonrigid image registration to solve this problem. MATERIALS AND METHODS: For
      each patient, a native image and a contrast image are recorded, respectively,
      before and after contrast administration. The native image is registered to the
      contrast image using an automatic intensity-based nonrigid three-dimensional
      registration algorithm. Both images are merged in a fused image, allowing the
      user to switch between a view of the arteries, the bone or both. The procedure
      has been applied to 95 patients. RESULTS: In all cases, subtraction CTA using
      nonrigid registration allows for a significantly better artifacts removal than
      subtraction CTA without registration. Image quality of all images was judged
      adequate for clinical use. The average total processing time for each dataset is
      about 30 minutes. CONCLUSION: Nonrigid registration can allow for a great
      reduction in subtraction artifacts for subtraction CTA, resulting in a clear view
      of the vasculature.

PMID- 18035286
TI  - Cooperative learning as applied to resident instruction in radiology reporting.
AB  - RATIONALE AND OBJECTIVES: The study is designed to evaluate the effectiveness of
      an active form of resident instruction, cooperative learning, and the residents'
      response to that form of instruction. MATERIALS AND METHODS: The residents
      dictated three sets of reports both before and after instruction in radiology
      reporting using the cooperative learning method. The reports were evaluated for
      word count, Flesch-Kincaid grade level, advancement on clinical spectrum,
      clarity, and comparison to prior reports. The reports were evaluated for changes
      in performance characteristics between the pre- and postinstruction dictations.
      The residents' response to this form of instruction was evaluated by means of a
      questionnaire. RESULTS: The instruction was effective in changing the resident
      dictations. The results became shorter (P<.035), more complex (P<.0126), and
      demonstrated increased advancement on clinical spectrum (P<.0204). The resident
      response to this form of instruction was positive. One hundred percent or
      respondents indicated enjoyment working with their groups. Seventy-five percent
      stated they would like to participate in more cooperative learning activities.
      The least positive responses related to the amount of time devoted to the
      project. Sixty-three percent of respondents stated that the time devoted to the
      project was appropriate. CONCLUSION: Cooperative learning can be an effective
      tool in the setting of the radiology residency. Instructional time requirements
      must be strongly considered in designing a cooperative learning program.

PMID- 18035289
TI  - Which actions of local anesthetics are relevant to the medical care of humans?

PMID- 18035290
TI  - Local anesthetics have different mechanisms and sites of action at recombinant 5
      HT3 receptors.
AB  - BACKGROUND AND OBJECTIVES: In addition to their blockade of voltage-dependent
      sodium channels, the action of local anesthetics at 5-hydroxytryptamine-3 (5-HT3)
      receptors may be clinically relevant. Because local anesthetics have different
      clinical properties, we have tested the hypothesis that differences in
      interactions at the 5-HT3 receptor may be clinically relevant by investigating
      the effects of 4 local anesthetics on recombinant wild-type and 4 mutant 5-HT3A
      receptors. METHODS: The cRNAs from human wild-type and 4 mutant 5-HT3A subunit
      clones were synthesized in vitro and expressed in Xenopus oocytes. Four mutant
      receptors were obtained by site-directed mutagenesis in the N-terminal
      extracellular region, which contains the agonist binding domain. Tryptophan (W)
      at positions 62 and 155 were replaced by tyrosine (Y) and glutamate (E) at
      position 101 by aspartate (D) or asparagine (N). The 2-electrode voltage clamp
      technique was used to measure peak currents induced by 5-HT in these receptors in
      the presence and absence of local anesthetics. RESULTS: All local anesthetics
      inhibited 5-HT-induced currents in a dose-dependent manner in the wild-type
      receptor. Inhibition by procaine and tetracaine were competitive whereas those of
      bupivacaine and lidocaine were both noncompetitive and competitive. The 4 mutants
      (W62Y, W155Y, E101D, E101N) could all form functional receptors. All mutant
      receptors exhibited a major increase (> 10-fold) in the half-maximum inhibitory
      concentration for procaine. The half-maximum inhibitory concentrations of
      tetracaine, bupivacaine, and lidocaine in mutant receptors were increased 2- to 3
      fold except that of tetracaine in W62Y receptor (6-fold). CONCLUSIONS: The ester
      type local anesthetics, procaine and tetracaine, may act at a different site on
      the 5-HT(3A) receptor and with a different mechanism than the amide-type local
      anesthetics. Clinical differences between local anesthetics may be at least
      partially due to differences in interactions at the 5-HT3A receptor.

PMID- 18035291
TI  - Effect of lumbar flexion on the extent of epidural blockade.
AB  - BACKGROUND AND OBJECTIVES: This study examined the effect of lumbar flexion on
      the extent of the epidural block during lumbar epidural anesthesia. METHODS: The
      epidural catheter was introduced at the L3-4 interspace with the patient in the
      lateral decubitus position with the surgical side down. After administering a
      test drug (3 mL of 2% lidocaine and 15 mug of epinephrine), the patients were
      randomly allocated to 1 of 2 groups: Group F (n = 16, lumbar spine flexed) and
      Group N (n = 17, lumbar spine in the neutral position). In both groups, 2%
      lidocaine (16 mL) mixed with sodium bicarbonate (2 mL) was administered through
      the epidural catheter while the patient maintained the lateral decubitus position
      with the lumbar spine either flexed or in the neutral position. All the patients
      maintained their respective positions for 5 minutes and were subsequently turned
      to the supine position. The pinprick block level and the degree of motor blockade
      were assessed every 10 minutes for 60 minutes after administering the local
      anesthetics. A 2-dermatomal difference in uppermost block between groups was
      determined to be clinically significant. RESULTS: The median difference between
      groups in the uppermost pinprick block level was only 1.5 dermatomes and it did
      not satisfy our criteria for clinical significance. There were no significant
      differences between the 2 groups in the lowermost pinprick block level and the
      degree of motor block. CONCLUSIONS: Lumbar flexion has no clinically relevant
      effect on sensory spread during epidural anesthesia.

PMID- 18035292
TI  - Postoperative epidural analgesia after total knee arthroplasty with sufentanil 1
      microg/ml combined with ropivacaine 0.2%, ropivacaine 0.125%, or levobupivacaine
      0.125%: a randomized, double-blind comparison.
AB  - BACKGROUND AND OBJECTIVES: Total knee replacement is associated with severe
      postoperative pain that, if treated insufficiently, interferes with early
      rehabilitation. The purpose of the present study is to compare the efficacy of
      ropivacaine (0.2% and 0.125%) and levobupivacaine (0.125%), all in combination
      with sufentanil 1 microg/mL with regard to postoperative pain relief and absence
      of motor block in a patient-controlled epidural analgesia setting. METHODS: The
      study design was randomized and double-blind. Sixty-three patients scheduled for
      total knee replacement under combined spinal-epidural anesthesia were randomly
      allocated to receive ropivacaine 0.2%/sufentanil 1 microg/mL (group 1),
      ropivacaine 0.125%/sufentanil 1 microg/mL (group 2), or levobupivacaine
      0.125%/sufentanil 1 microg/mL (group 3) for postoperative epidural pain relief.
      Primary endpoints were numerical rating scores for pain and patient satisfaction,
      motor block scores, time to first demand of the patient-controlled epidural
      analgesia device and average hourly consumption of local anesthetic and
      sufentanil. RESULTS: There were no significant differences between the 3 groups
      regarding numerical rating scores for pain, patient satisfaction, and motor block
      scores at any of the time intervals; time to first demand and average hourly
      sufentanil consumption were similar. Patients in group 1 used significantly more
      local anesthetic than patients in groups 2 and 3. CONCLUSIONS: All 3 solutions
      provided adequate analgesia and minimal motor block. The higher concentration of
      ropivacaine 0.2% was associated with a higher consumption of local anesthetic and
      did not result in a decrease in the consumption of sufentanil. Under the
      conditions of this study, patient-controlled epidural analgesia consumption of
      the epidural mixture was predominantly determined by sufentanil.

PMID- 18035293
TI  - Skin temperature after interscalene brachial plexus blockade.
AB  - BACKGROUND AND OBJECTIVES: In neuraxial anesthesia, increase of skin temperature
      is an early sign of successful block. Yet, during peripheral nerve block of the
      lower extremity, increase in skin temperature is a highly sensitive, but late
      sign of a successful block. We hypothesized that after interscalene brachial
      plexus block, a rise in skin temperature follows impairment of sensation during
      successful nerve block and occurs only distally, as observed in the lower
      extremity. METHODS: In the present study, we prospectively evaluated the changes
      in skin temperature after interscalene brachial plexus blockade in 45 patients
      scheduled for elective shoulder surgery. We assessed pinprick and cold sensation
      as well as skin temperature at sites of the skin innervated by the median, ulnar,
      radial, axillary and musculocutaneous nerve. RESULTS: At the skin areas
      innervated by the axillary and musculocutaneous nerve, skin temperature did not
      increase after successful block. At the distal sites, innervated by the median,
      ulnar, and radial nerve, skin temperature increased significantly (1.9-2.1
      degrees C within 30 min) after successful block while it did not after failed
      nerve block or on the contralateral side. In these areas attenuation of skin
      sensation preceded a measurable rise in skin temperature (> or =1 degrees C) in
      56.3% of nerve blocks, occurred at the same time in 35.2%, and in 8.5% the
      temperature rise occurred first. CONCLUSIONS: Assessment of skin temperature
      cannot predict the success of an interscalene brachial plexus block of the
      axillary and musculocutaneous nerve. Distally, the increase of skin temperature
      has a high sensitivity and specificity but occurs later than the loss of sensory
      and motor functions. Therefore, the measurement of skin temperature during
      interscalene blockade is of limited clinical value.

PMID- 18035294
TI  - Modified lateral block of the suprascapular nerve: a safe approach and how much
      to inject? A morphological study.
AB  - BACKGROUND AND OBJECTIVES: This paper presents an evaluation of a modified
      lateral suprascapular nerve block with easy orientation, low risk of displacement
      of the needle, and with an assessment of 2 different volumes to propose an ideal
      volume for a successful block. METHODS: Both shoulders of 34 cadavers were
      investigated. Insertion point of the needle was determined in the angle of the
      lateral end of the clavicle, acromion, and the spine of the scapula. The needle
      was directed toward the medial, dorsal, and caudad direction. Ten mL of diluted
      contrast agent for computerized tomography was injected in the 34 right sides
      (group A) and 5 mL in the 34 left sides (group B). Immediately after injection,
      all shoulders were investigated by computerized tomography scans and 3
      dimensional reconstruction to document the constrast dissemination. Five sides of
      each group were injected with colored contrast and dissected after computerized
      tomography investigation. RESULTS: Group A showed a distribution to the entire
      supraspinous fossa in all cases and the contrast was pressed out of the
      suprascapular notch in 4 cases with a maximal extension into the axillary fossa
      in 3 cases. In group B, the supraspinous fossa was filled in 24 cases, with a
      maximal extension to the axillary fossa in 2 cases. In 9 cases, the contrast
      agent stayed in the lateral half of the supraspinous fossa. In 1 case we had a
      medial spread only which still surrounded the suprascapular notch, in another
      case a superficial spread with misplacement of the needle. CONCLUSION: Based on
      this cadaver study, the lateral modified approach appears to be a safe technique
      for a suprascapular nerve block, which might be preferred as a single shot
      technique. A 5 mL volume appears sufficient to fill the supraspinous fossa and to
      reach the suprascapular nerve, which branches in this anatomical compartment.

PMID- 18035295
TI  - Factors predicting success and failure for cervical facet radiofrequency
      denervation: a multi-center analysis.
AB  - BACKGROUND AND OBJECTIVES: The concept of radiofrequency denervation has recently
      come under question in light of several studies showing minimal to no benefit.
      One possibility proposed for these negative outcomes is poor selection criteria.
      Unlike virtually all other spine interventions, the factors associated with
      success and failure for cervical facet denervation have yet to be determined. The
      purpose of this study is to determine which demographic, clinical and treatment
      factors are associated with cervical facet radiofrequency denervation outcomes.
      METHODS: Data were garnered from 3 academic medical centers on 92 patients with
      chronic neck pain who underwent radiofrequency denervation after a positive
      response to diagnostic local anesthetic blocks. Success was defined as at least
      50% pain relief lasting at least 6 months. Variables evaluated for their
      association with outcome included age, sex, duration of pain, opioid use, pain
      referral pattern, paraspinal tenderness, pain exacerbated by extension/rotation,
      magnetic resonance image abnormalities, diabetes, smoking, scoliosis, obesity,
      prior surgery, and levels treated. RESULTS: The only clinical variable associated
      with success was paraspinal tenderness. Factors associated with treatment failure
      included radiation to the head, opioid use, and pain exacerbated by neck
      extension and/or rotation. CONCLUSIONS: Selecting patients based on key clinical
      variables may increase the chance of treatment success for cervical facet
      radiofrequency denervation.

PMID- 18035296
TI  - Carl Koller Gold Medal Award to Paolo Busoni at the Silver Anniversary ESRA
      Annual Congress, Monte Carlo, Monaco, September 6-9, 2006.

PMID- 18035299
TI  - Three-dimensional, multiplanar, ultrasound-guided, radial nerve block.
AB  - OBJECTIVE: We describe the use of 3-dimensional, multiplanar ultrasound imaging
      for peripheral nerve block. CASE REPORT: To illustrate the potential usefulness
      of the technique, we present a case in which real-time 3-dimensional, multiplanar
      ultrasound was used to assist in the performance of a radial nerve block.
      CONCLUSIONS: Three-dimensional, multiplanar ultrasound in real-time has the
      potential to improve nerve identification and accuracy of needle placement in
      regional anesthesia.

PMID- 18035298
TI  - Celiac plexus blockade in children using a three-dimensional fluoroscopic
      reconstruction technique: case reports.
AB  - BACKGROUND AND OBJECTIVES: We present three cases wherein a new radiologic
      technique was used to facilitate performance of retrocrural celiac plexus
      blockade. Three patients presented to our institution for performance of celiac
      plexus block for relief of intractable upper abdominal pain. One carried the
      diagnosis of chronic pancreatitis, one abdominal pain and gastrointestinal
      dysmotility, the other adrenocortical carcinoma. METHODS: We applied the
      technology used in 3-dimensional rotational angiography to determine spread of
      the injected medication in three dimensions, and facilitate the blocks. RESULTS:
      Three-dimensional rotational angiography was used with clinical success.
      CONCLUSIONS: Three-dimensional rotational angiography shows promise for
      understanding the spread of medication necessary to accomplish a successful
      block, and may help explain failures in cases where anatomic distortion may
      interfere with proper injectate flow.

PMID- 18035300
TI  - Posterior lumbar plexus block in children: a new anatomical landmark.
AB  - BACKGROUND AND OBJECTIVES: Posterior lumbar plexus block is a well established
      anesthetic technique for lower limb surgeries. Both magnetic resonance imaging
      and clinical prospective studies were performed to verify if a new palpable
      landmark could be used for lumbar plexus block in pediatric patients. METHODS:
      Twenty-five magnetic resonance imaging exams were analyzed to verify the
      relationship between the ipsilateral lumbar plexus and the sulcus formed by the
      division between the longissimus and the iliocostal muscles. The mean angle
      between the point of needle introduction and the lumbar plexus was measured. In a
      prospective series, 100 consecutive patients (1 to 15 years old) were given
      posterior lumbar plexus block. Under general anesthesia, the first palpable
      depression found by sliding the finger laterally at the L4 spine level was used
      as a landmark. A needle was introduced perpendicularly at the point where this
      sulcus crossed the line connecting the iliac crests. The ease of sulcus
      palpation, time spent in the block procedure, and postoperative pain score at 3
      time points (M1, awake; M2, discharge from the postanesthesia care unit; M3, the
      fifth postoperative hour) were registered. RESULTS: The mean angle found in 25
      magnetic resonance images was 5.6 degrees. Clinical data from 99 patients were
      analyzed. The intramuscular groove was easily palpable in 93% of the patients.
      More than 95% of the blocks were completed in less than 5 minutes. The median
      pain scores were 0 for M1/M2 and 1 for M3. The block was effective in 97% of
      patients (95% confidence interval, 93.6%-100%). There was 1 case of subarachnoid
      puncture (95% confidence interval, 0%-3%). CONCLUSIONS: The sulcus formed by the
      division between the longissimus and the iliocostal muscles is a simple, direct,
      and easy-to-identify landmark for posterior lumbar plexus block in children.

PMID- 18035301
TI  - Stimulating catheter as a tool to evaluate peripheral nerve function during hip
      rotationplasty.
AB  - OBJECTIVE: Stimulating catheters have been introduced into clinical practice to
      confirm perineural localization of the catheters. The muscular twitch induced
      over the catheter may be used to evaluate nerve function intraoperatively.
      Therefore, the function of the sciatic nerve was evaluated during major cancer
      surgery of the femur. CASE REPORT: A 7-year-old boy (29 kg) was scheduled for hip
      rotationplasty for resection of an osteosarcoma of the left femur under general
      anesthesia and postoperative pain therapy with an epidural stimulating catheter.
      In hip rotationplasty the femur is resected, the lower limb and foot are rotated
      180 degrees and the tibia plateau is attached to the pelvic acetabulum to form a
      new hip joint. During preparation of the left thigh and the sciatic nerve, motor
      responses to stimulation of the catheter were preserved, but the stimulation
      threshold increased. After vascular anastomosis the foot remained cold, therefore
      ropivacaine was applied epidurally and subsequently a warming of the foot was
      observed. At the end of the operation, the patient was free of pain, a good
      capillary pulse of the leg was observed, and the patient was able to move the
      foot and toes of the rotated leg. CONCLUSIONS: The use of epidural stimulating
      catheters as a tool to monitor nerve function is a novel and simple procedure to
      monitor nerve function intraoperatively and to enable good postoperative pain
      control.

PMID- 18035302
TI  - Bee stings--a remedy for postherpetic neuralgia? A case report.
AB  - OBJECTIVE: This case report describes the effects of bee stings on painful
      postherpetic neuralgia in a 51-year-old man. CASE REPORT: The patient was stung
      by 3 bees in the distribution in which he had been experiencing postherpetic
      neuralgia. One day after the bee stings, the patient's painful postherpetic
      neuralgia was completely relieved, and the relief lasted for 1 and a half months.
      Subsequently, the patient's pain returned, but at significantly less intensity
      and frequency than what he had experienced prior to the bee stings. CONCLUSIONS:
      Bee venom and bee sting therapy have been shown to have both antinociceptive and
      anti-inflammatory properties, which may explain why the bee stings relieved the
      patient's postherpetic neuralgia. Bee sting or bee venom therapy should be
      further investigated as a potential treatment modality for postherpetic
      neuralgia.

PMID- 18035303
TI  - Imaging in anesthesia: the role of 4 MHz to 7 MHz sector array ultrasound probe
      in the identification of the sciatic nerve at different anatomic locations.

PMID- 18035304
TI  - A new look at the paravertebral block: a percutaneous video-assisted technique.

PMID- 18035305
TI  - Obturator nerve anatomy and ultrasound imaging.

PMID- 18035306
TI  - Rediscovery of ganglion impar block via coccygeal joints.

PMID- 18035307
TI  - Comparison of two 3.5 inch hustead needles.

PMID- 18035308
TI  - High thoracic epidural plus suprascapular nerve block analgesia for
      thoracoscapular fusion.

PMID- 18035309
TI  - Ultrasound, paresthesia, and motor response.

PMID- 18035311
TI  - Seeds, trees, and shade-personal experience in research career development.

PMID- 18035312
TI  - Reply to Drs. Joshi, Kehlet, and Rawal. Acute postsurgical pain management: a
      critical appraisal of current practice.

PMID- 18035313
TI  - Ultrasound and regional anesthesia techniques--is there any limitation?

PMID- 18035314
TI  - Unintentional transient sciatic nerve block after knee infiltration with local
      anesthetics.

PMID- 18035315
TI  - Saphenous nerve block technique with neurostimulation.

PMID- 18035316
TI  - B cell targeted therapies. Introduction.

PMID- 18035317
TI  - B lymphocytes and Epstein-Barr virus: the lesson of post-transplant
      lymphoproliferative disorders.
AB  - Epstein-Barr virus (EBV) is a ubiquitous human gamma-herpes virus that
      establishes a life-long asymptomatic infection in immunocompetent hosts by
      colonizing memory B lymphocytes and hijacking cellular signaling pathways that
      regulate antigen-dependent B-cell activation and differentiation. In patients
      with solid organ or hematopoietic stem cell transplantation, the defect in EBV
      specific immune responses may allow the outgrowth of EBV-carrying B lymphocytes
      that may give rise to a spectrum of different clinico-pathologic entities
      encompassed by the term post-transplantation lymphoproliferative disorders
      (PTLD). EBV-driven immortalization of B-cells is mediated by the cooperative
      activity of viral proteins that derange critical cellular pathways controlling
      growth and/or survival of B lymphocytes. Full transformation of infected B-cells
      is achieved by the contribution of poorly defined additional co-factors,
      including microenvironmental stimuli, genetic and epigenetic alterations. The
      quantification of circulating EBV DNA and EBV-specific T cells are valuable tools
      in the clinical monitoring of EBV-associated PTLD. The recent advances in
      elucidation of the mechanisms underlying EBV-induced growth transformation will
      be instrumental in guiding the design of novel approaches for the treatment of
      these often life-threatening lymphoproliferative disorders.

PMID- 18035318
TI  - Signaling pathways activated by antigen-receptor engagement in chronic
      lymphocytic leukemia B-cells.
AB  - Several features of the B-cell receptor (BCR) have emerged as major prognostic
      factors in chronic lymphocytic leukemia (CLL). In particular, the absence of
      somatic mutations in the immunoglobulin variable region genes and expression of
      the protein tyrosine kinase ZAP-70 are strongly associated with an aggressive
      clinical course, and both features have been correlated with a greater capacity
      of the BCR to transmit antigen-induced signals. Additionally, differences in BCR
      structure and reactivity indicate that CLL B-cells from the two prognostic
      subsets may recognize different types of antigens. Antigens that are not rapidly
      internalized induce sustained BCR signaling that can promote the survival of the
      leukemic B-cells. The BCR signal is initially transmitted by the Syk kinase and
      modulated by ZAP-70, which shows inefficient or absent tyrosine kinase activation
      in B-cells. However, both ZAP-70 expression and sustained BCR engagement have
      been associated with prolonged activation of the Akt and ERK kinases, which is
      required for the induction of several antiapoptotic proteins, including Mcl-1,
      Bcl-xL and XIAP. Therefore, targeting components along the BCR signaling pathway
      may be a promising strategy for the treatment of CLL.

PMID- 18035319
TI  - Infections, B cell receptor activation and autoimmunity: different check-point
      impairments lead to autoimmunity, clonal B cell expansion and fibrosis in
      different immunological settings.
AB  - B cells as autoantibody producing cells are major players in several autoimmune
      chronic inflammatory diseases (ACIDs). In some particular settings (i.e.
      Sjogren's syndrome, rheumatoid arthritis), the activated B cells could undergo
      malignant clonal expansion. Chronic infections by lymphotropic viruses (hepatitis
      C virus, Epstein Barr Virus, Herpes 6 and 8 viruses) could amplify the activation
      process by inducing antiapoptotic signals that lead to a longer survival of B
      cell subsets. This might then lead, through multiple oncogenic events, to benign
      first and malignant thereafter clonal B cell expansion. Understanding how the B
      cell are activated, how the B cell receptor activation can be maintained under
      control, which check-points could be deregulated and lead to a persistent
      activation is of crucial importance in benign and malignant diseases. The
      evidence suggests that the B cells faulty check-points are different in chronic
      lymphocytic leukaemia, in cryoglobulinemia, rheumatoid arthritis, systemic lupus
      erythematosus and systemic sclerosis.

PMID- 18035320
TI  - B-cells and mixed cryoglobulinemia.
AB  - Mixed cryoglobulinemia (MC) is a systemic small-vessel vasculitis; B-cell
      expansion is the biological substrate of the disease. It can be regarded as
      benign lymphoproliferative condition that may evolve to frank lymphoma. HCV
      infection is the main causative factor of MC, as well as of other overlapping
      disorders, through multifactorial and multistep pathogenetic process. HCV-related
      B-cell proliferation represents an important model of virus-driven
      autoimmune/neoplastic disorder. The term HCV syndrome is referred to a wide
      spectrum of both hepatic and extrahepatic disorders. The present review analyzes
      the complex virological, clinico-pathological, and therapeutic implications of B
      cell proliferation, with or without HCV infection, in MC patients.

PMID- 18035321
TI  - Stimulatory autoantibodies to the PDGF receptor: a link to fibrosis in
      scleroderma and a pathway for novel therapeutic targets.
AB  - Systemic sclerosis (scleroderma) is a complex disease characterized by excessive
      deposition of collagen and abnormalities of blood vessels. In addition,
      activation of the immune system is a central feature of scleroderma as shown by
      mononuclear cell infiltration of the skin, autoantibody production and release of
      inflammatory cytokines. The pathogenesis of the disease is poorly understood and
      the molecular events underlying the main clinical features are not known. The
      detection of agonistic autoantibodies targeting PDGF receptor in serum of
      patients with scleroderma may indicate a novel link between phenotypic features
      of the disease and a specific signalling pathway. Agonistic PDGF receptor
      antibodies induce in vitro the scleroderma phenotype in normal human fibroblasts
      and, thus, link autoimmunity to fibrosis. These findings pave the way to novel
      therapeutic strategies.

PMID- 18035322
TI  - From normal to clonal B cells: Chronic lymphocytic leukemia (CLL) at the
      crossroad between neoplasia and autoimmunity.
AB  - Chronic lymphocytic leukemia (CLL) is a B-cell malignancy endowed with a number
      of features that recall autoimmune disorders, including the CD5 expression and
      the development of autoimmune manifestations restricted to self antigens
      expressed by hematopoietic cells. Several evidences strongly support the
      possibility that an antigenic stimulation through the B-cell receptor (BCR) is
      involved in the selection and possibly also the expansion of the malignant clone.
      Though all evidences suggest specific Ag recognition and possibly stimulation at
      different time-points, the nature of the Ag(s) is still unknown. It appears
      likely that CLL cells derive from a pool of auto/polyreactive CD5(+) B cells.
      Hence CLL appears to be a B-cell malignancy triggered or facilitated in its
      development and evolution by an auto-Ag. The crucial issues have become to what
      extent this deleterious binding capacity is central to the natural history of the
      disease and how it relates to the malignant transformation of the cell.

PMID- 18035323
TI  - B cells and herpesviruses: a model of lymphoproliferation.
AB  - Unlike alpha- and beta-herpesviruses, human gamma-herpesviruses, including the
      Epstein-Barr virus (EBV) and the human herpesvirus-8 (HHV-8), are B lymphotropic
      viruses. Primary infection with EBV, in otherwise healthy subjects, causes a
      benign lymphoproliferative syndrome, the mononucleosis syndrome. However, several
      epidemiologic and biologic studies have shown a pathogenetic role of EBV in the
      development of human B cell lymphomas, both in immunocompetent and in
      immunosuppressed individuals. HHV-8 is the necessary etiologic agent of a lymph
      vascular tumor, the Kaposi sarcoma, but it is also implicated in the pathogenesis
      of rare B cell lymphoproliferative disorders, mainly occurring in the setting of
      immunosuppression. The aim of this review is to provide an updated description of
      the different strategies used by these two herpesviruses to influence B cell fate
      decisions. Both EBV and HHV-8 have evolved specific mechanisms in order to: (1)
      interact with the B cell developmental machinery; (2) allow infected B cells to
      escape from the control of the immune system; (3) affect the B cell cycle
      checkpoints; (4) mimic and influence B cellular proliferation and differentiation
      pathways. Understanding the mechanisms of herpesvirus induced B cell
      lymphoproliferation will provide the basis for novel treatment approaches in
      patients with EBV and HHV-8 related lymphomas.

PMID- 18035324
TI  - B cells in rheumatoid arthritis.
AB  - Though its etiology remains unknown thus far, the role that autoimmune processes
      play in rheumatoid arthritis (RA) pathogenesis has been widely proven. Given the
      easier accessibility of humoral components, the first feature of this
      contribution to be recognized has been the occurrence of the so-called rheumatoid
      factor in a large proportion of RA patients. This antibody recognizes the Fc
      portion of human IgG. By investigating RA pathologic processes and also through
      experimental models where immune complexes play a fundamental role, many other
      autoantibodies have then come to our knowledge to be associated with the disease.
      Their presence and persistence implies that clones of autoreactive B cells
      survive and proliferate in RA patients under a continuous stimulation. Whether
      this is a mechanism of disease initiation or just an epiphenomenon is still
      unclear but no doubt exists that autoantibodies represent a very useful tool in
      both diagnostic and prognostic terms. Being much more than simple autoantibody
      producers, B cells are able to secrete many important cytokines and to
      efficiently present antigens to T lymphocytes in the synovial environment. All of
      these functions are essential in the development of RA, and lately have claimed
      attention as B cell depletion has become a common and effective strategy of
      treatment in RA.

PMID- 18035325
TI  - B cells in SLE: different biological drugs for different pathogenic mechanisms.
AB  - Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized
      by a complex multi-factorial pathogenesis and a great clinical polymorphism. SLE
      is considered to be a B cell disease in which autoantibodies are the major
      players. Recently, the central role of B cells has been confirmed and it has been
      shown that that the relative frequency of B cells subsets is altered in SLE
      patients. Conventional immunosuppressive therapies such as azathioprine,
      cyclophosphamide or methotrexate, reduce disease activity and improves the
      patient's general health conditions. These treatments have possible side effects;
      in fact they could compromise liver function, fertility and innate and adaptive
      immune responses. Moreover, for unknown reasons a small group of SLE patients is
      refractory to immunosuppressive therapy. In these cases finding an effective
      treatment becomes a challenge. The progress in therapeutic antibody technology
      has led to the production of a wide array of humanized monoclonal antibodies,
      targeting specific cell types or pathways, initiating a new era in the treatment
      of autoimmune disorders. In contrast to general immuno-suppression, the
      availability of drugs interfering with specific pathogenetic pathways gives the
      possibility to choose therapies tailored to each disease in each patient.

PMID- 18035326
TI  - The paradox of CD5-expressing B cells in systemic lupus erythematosus.
AB  - The pathophysiological relevance of B cells for systemic lupus erythematosus
      (SLE), particularly those expressing the T-cell marker CD5, raises the question
      as to how they operate upon autoimmune processes. Based on their production of
      low-affinity multispecific antibodies (Abs), CD5(+) B lymphocytes, also referred
      to as B1 cells, have originally been endowed with the autoAb making. It has since
      been established that high-affinity Abs to double-stranded DNA are not generated
      by these cells, but rather by B2 cells. It does not appear that they have the
      exclusive rights to the production of pathogenic autoAbs. In the light of recent
      findings, CD5 plays a paradoxical role in preventing autoimmunity. Hence,
      misguided signaling through CD5 could lead to autoimmunity. This provocative view
      differs from the naive interpretation that the increased levels of B1 cells in
      SLE represent a direct source of autoAbs responsible for damaging organs.

PMID- 18035327
TI  - RAG-mediated secondary rearrangements of B-cell antigen receptors in rheumatoid
      synovial tissue.
AB  - Rheumatoid arthritis (RA) induces major changes in synovial tissue (ST) and
      cartilage and bone destruction. Still, its pathogenesis is poorly understood.
      Accumulating evidence points to an important role for B lymphocytes. Rheumatoid
      ST is characterized by activation of the synoviocytes and infiltrated by various
      inflammatory cells such as B and T lymphocytes. The infiltrate is diffuse or
      organized as germinal centers (GCs). These accommodate the immune response and
      favor self-tolerance breakdown. Receptor revision in B cells results from re
      expression of the recombination activating genes (RAGs) which reinitiate
      immunoglobulin gene recombination, and modify the B-cell antigen receptor
      accordingly. In rheumatoid ST, secondary VDJ rearrangements occur and RAG
      proteins are detected. The mechanism that triggers and controls this revision
      remains elusive. We favor the hypothesis that such an uncontrolled process leads
      to autoimmunity.

PMID- 18035328
TI  - Liquids in the lung.

PMID- 18035329
TI  - Seasonal phenology, host-blood feeding preferences and natural Leishmania
      infection of Phlebotomus perniciosus (Diptera, Psychodidae) in a high-endemic
      focus of canine leishmaniasis in Rome province, Italy.
AB  - A 2-year survey aimed to study seasonal phenology, host-blood feeding preferences
      and Leishmania infections of Phlebotomus perniciosus, was carried out in a high
      endemic focus of canine leishmaniasis in Rome province, Italy. Sandfly densities
      were monitored by sticky traps, while CDC light traps and hand collections were
      used for individual sandfly analyses. Four species were identified, three
      belonging to Phlebotomus (P. perniciosus, Phlebotomus mascittii and Phlebotomus
      papatasi) and one to Sergentomyia (Sergentomyia minuta) genera. In sticky traps,
      P. perniciosus (53.5%) and S. minuta (46.0%) were the prevalent species, whereas
      specimens collected by CDC light traps and hand collections consisted mostly of
      P. perniciosus. The study showed a markedly different sandfly density between
      2003 and 2002 collections (5024 specimens versus 644 specimens, respectively),
      which was attributed to different climatic conditions. In 2003 adults were active
      during 7 months (May-November) with a typical bimodal distribution, while in 2002
      their activity was shorter (5 months, June-October) without clear density peaks.
      In this low-density year, the prevalence of P. perniciosus was significantly
      higher in domestic than in wild resting sites. Blood meal tests showed that P.
      perniciosus had no preferences for any of the two Leishmania susceptible hosts,
      being the forage ratio rate 0.7 and 1.0 for man and dog, respectively. A
      significant number of P. perniciosus was found with avian (60.3%) or ovine
      (24.2%) blood, that was in relation with the habitats where fed specimens were
      collected. The rate of specimens of P. perniciosus without blood and found
      positive for Leishmania DNA, detected by a sensitive nested-PCR technique, was
      much higher (27.6%) than the promastigote infection rate determined by microscopy
      in the dissected females (1.4%). The intense Leishmania transmission in the study
      area was confirmed by the high prevalence of anti-leishmanial antibodies in dogs
      (33.3%).

PMID- 18035330
TI  - Doctor, my son is so tired... about a case of hereditary fructose intolerance.
AB  - We present the case of a 17-year-old male who was diagnosed at birth with
      hereditary fructose intolerance (HFI). The patient complained of morning-time
      asthenia and post-prandial drowsiness despite a correct sleep pattern. The
      physical examination and biological check-up only showed severe vitamin C
      deficiency (<10 mol/l; normal range: 26-84). The patient's tiredness was
      attributed to this vitamin C deficiency, which is a frequent side-affect of the
      fructose-free diet. A change in diet associated with a supplementation in vitamin
      C was advised, with an increase in vegetable intake, principally avoiding
      carrots, onions, leaks and tinned sweet-corn. This case offers the opportunity
      for a review of this rare disease. Two kinds of fructose metabolism disorders
      (both autosomal recessive) are recognized: 1) essential fructosuria caused by a
      deficiency of fructokinase, which has no clinical consequence and requires no
      dietary treatment; 2) HFI, linked to three main mutations identified in aldolase
      B gene that may be confirmed by fructose breath test, intravenous fructose
      tolerance test, and genetic testing. In HFI, fructose ingestion generally induces
      gastro-intestinal (nausea and vomiting, abdominal pain, meteorism) and
      hypoglycemic symptoms. Fasting is well tolerated. If the condition remains
      undiagnosed, it leads to liver disease with hepatomegaly, proximal tubular
      dysfunction, and slow growth and weight gain. In conclusion, endocrinologists
      should be aware of this rare metabolic disease in order to provide careful follow
      up, particularly important when the patient reaches adulthood. Moreover,
      hypoglycemia induced by fructose absorption, unexplained liver disease, irritable
      bowel syndrome or familial gout in an adult is suggestive of the diagnosis.

PMID- 18035331
TI  - Imagery rescripting in cognitive behaviour therapy: images, treatment techniques
      and outcomes.
AB  - Although imagery rescripting has long been part of cognitive behaviour therapy
      (CBT), recent years have seen a growing interest in the use of imagery
      rescripting interventions in CBT, especially with patients who struggle with
      distressing, intrusive imagery. This growth in the clinical applications of
      imagery has led to the creation of the current special issue of collected papers
      on imagery rescripting, which is designed to: (a) present research and clinical
      applications of imagery rescripting techniques to problematic mental imagery, (b)
      consider problematic imagery across a wide range of psychological disorders that
      might be a target for imagery rescripting (including novel areas such as mental
      contamination, bulimia and suicidality), (c) explore a variety of imagery
      rescripting techniques in the treatment of PTSD, as well as depression, social
      phobia, and snake phobia, and (d) stimulate interest for future treatment
      innovation in the use of imagery rescripting techniques to address other clinical
      disorders. The aim of this editorial is to summarise the collected papers
      presented and the links between them. A working definition of two types of
      imagery rescripting is provided, along with a heuristic framework for
      conceptualising the range of imagery techniques in cognitive therapy.

PMID- 18035332
TI  - Ageing and atherosclerosis: Mechanisms and therapeutic options.
AB  - Atherosclerosis is the cause of most heart attacks and strokes, and is par
      excellence, a disease of ageing. Whilst disease prevalence and incidence
      increases with increasing decade of life, there is also evidence of accelerated
      cellular ageing in atherosclerosis. Such evidence includes impaired cell
      proliferation, early culture senescence and cell cycle markers of senescence in
      vitro and in vivo. Cell senescence is also characterised by loss of telomeres
      from the ends of chromosomes. Cellular ageing increases with disease severity,
      acting as a marker for disease, but also directly promotes atherosclerosis.
      Cellular ageing appears to be due to both abnormal proliferation of cells in an
      attempt to repair vessel damage, and a response to the damage itself. This review
      summarises the evidence of vascular cell senescence in atherosclerosis, the
      causes and consequences of accelerated cellular ageing in atherosclerosis, and
      identifies potential therapeutic options for both prevention and treatment.

PMID- 18035333
TI  - WRC-213, an l-methionine-conjugated mitoxantrone derivative, displays anticancer
      activity with reduced cardiotoxicity and drug resistance: identification of
      topoisomerase II inhibition and apoptotic machinery in prostate cancers.
AB  - Anthracyclines and anthracenediones are well-known cancer chemotherapeutic agents
      but their uses are limited with cardiotoxicity and drug resistance. Several l-
      and d-form amino acids were introduced into the anthraquinone skeleton and
      numerous derivatives were synthesized for the evaluation of anticancer activity.
      The screening tests showed that WRC-213, an l-methionine conjugation, was the
      most effective derivative to inhibit proliferative effect of human androgen
      independent prostate cancer PC-3 cells (IC50=50 nM). In an extension evaluation,
      WRC-213 displayed a potent anti-proliferative activity in various cancer cell
      lines, including non-small cell lung cancer A549, androgen-independent prostate
      cancer DU145, colorectal cancer HT-29, breast cancer MCF-7 and hepatocellular
      carcinoma Hep3B and HepG2. It induced cell-cycle arrest at S and G2, but not
      mitotic phase, in PC-3 cells. The comet assay revealed that induction of DNA
      damage and inhibition of topoisomerase II were the primary insults. After the
      checkpoint arrest of the cell-cycle, WRC-213 induced the mitochondria-mediated
      intrinsic apoptotic pathway, including Mcl-1 cleavage, Bcl-2 down-regulation and
      activation of caspase-9/caspase-3 cascades. Survivin degradation and caspase-2
      activation also contributed to WRC-213-induced apoptosis. Moreover, the
      assessment of cytotoxicity in H9c2 cardiomyocytes and drug resistance in NCI/ADR
      RES cells demonstrated that WRC-213 showed much lower cardiotoxicity and P
      glycoprotein-related resistance than those of mitoxantrone, etoposide and
      doxorubicin. In conclusion, it is suggested that WRC-213 is a potential
      topoisomerase II inhibitor with reduced cardiotoxicity and drug resistance. It
      inhibits topoisomerase II activity and induces chromosomal DNA strand breaks,
      leading to S and G2 arrest of the cell-cycle and activation of mitochondria
      mediated apoptotic pathways.

PMID- 18035334
TI  - Moderate degeneration of nigral neurons after repeated but not after single
      intrastriatal injections of low doses of 6-hydroxydopamine in mice.
AB  - Parkinson's disease (PD) is characterized by a bilateral progressive degeneration
      of nigrostriatal dopaminergic neurons. Among several toxin-induced animal models
      of PD, a single intrastriatal injection of 6-hydroxydopamine (6-OHDA) has been
      reported to provoke a retrograde degeneration of nigral dopaminergic neurons and
      may reflect an early stage of PD. However, the lack of a progressive neuronal
      loss in those acute models limits the suitability for the assessment of
      neuroprotective therapeutics. Therefore, we investigated if repeated
      microinjections of 6-OHDA into the striatum of mice may generate a subchronic
      model with progressive degeneration. In contrast to acute bilateral
      microinjections of 8 microg 6-OHDA, repeated daily intrastriatal applications for
      5 d provoked a moderate, but significant loss of nigral neurons. However, a
      longer treatment over 7 d failed to cause a more marked degeneration than
      observed after 5 d. Motor performance was unaltered after single and repeated
      treatments, except of a slight cataleptic behavior and shortened stride-length
      performance in mice treated over 7 d. The present data show for the first time
      that daily intrastriatal injections of 6-OHDA over 5 d can enhance the
      nigrostriatal neurodegeneration in mice. However, the extent of the neuronal loss
      was moderate and the technical expense limits the utility as a subchronic model.

PMID- 18035335
TI  - Reduction of cerebral infarction in rats by biliverdin associated with
      amelioration of oxidative stress.
AB  - Biliverdin (BV), one of the byproducts of heme catalysis through heme oxygenase
      (HO) system, is a scavenger of reactive oxygen species (ROS). We hypothesized
      that BV treatment could protect rat brain cells from oxidative injuries via its
      anti-oxidant efficacies. Cerebral infarction was induced by transient middle
      cerebral artery occlusion (tMCAO) for 90 min, followed by reperfusion. BV or
      vehicle was administered intraperitoneally immediately after reperfusion. The
      size of the cerebral infarction 2 days after tMCAO was evaluated by 2,3,5
      triphenyltetrazolium chloride (TTC) stain. Superoxide generation 4 h after tMCAO
      was determined by detection of oxidized hydroethidine. In addition, the oxidative
      impairment of neurons were immunohistochemically assessed by stain for lipid
      peroxidation with 4-hydroxy-2-nonenal (4-HNE) and damaged DNA with 8-hydroxy-2'
      deoxyguanosine (8-OHdG). BV treatment significantly reduced infarct volume of the
      cerebral cortices associated with less superoxide production and decreased
      oxidative injuries of brain cells. The present study demonstrated that treatment
      with BV ameliorated the oxidative injuries on neurons and decreased brain infarct
      size in rat tMCAO model.

PMID- 18035336
TI  - Knowledge inhibition and N400: a within- and a between-subjects study with
      distractor words.
AB  - We tested whether the N400 event-related potential (ERP) indexes the integration
      of semantic knowledge in the context or whether it indexes the inhibition of
      activated, but inappropriate, knowledge. A distractor-prime-target word sequence
      was presented in each trial. Subjects had to make semantic relatedness judgments
      on prime-target pairs. In the first experiment, subjects had an additional task.
      They either had to ignore or to attend to distractors. In critical conditions,
      that is, when distractors were related to targets, the times to make the prime
      target semantic relatedness judgments were longer when subjects had to attend to
      distractors than when they had to ignore them. In accordance with the inhibition
      hypothesis, the amplitudes of the N400 elicited by distractors were larger in the
      ignore than in the attend task. In the second experiment, the same distractor
      prime-target triplets were used. However, there was no additional task. Subjects
      only had to make the prime-target semantic-relatedness judgment. They were then
      split in two subgroups: the good ignorers, who did not take much longer to make
      the judgment in critical than in control conditions, and the poor ignorers, that
      is, those who did take much longer. Results were again consistent with the
      inhibition idea. The amplitudes of the N400s evoked by distractors were larger in
      the good than in the poor ignorers [corrected]. The results of these two studies
      are taken together to support the idea that N400 index a semantic inhibition
      rather than an integration effort.

PMID- 18035337
TI  - The influence of eye movements on the temporal features of executed and imagined
      arm movements.
AB  - The very close coordination between eye and hand indicates that eye movements are
      parts of the neural processes underlying the planning and control of arm
      movements. Eye movements are fundamental during observed actions and play a
      functional role in visual mental imagery. However, the role of eye movements
      during imagined actions is still unknown. Here, we report the timing features of
      eye and arm pointing movements for nine healthy participants in four conditions:
      Executed movements with orientation saccades (Eyes Free) or with no saccades
      (Eyes Motionless), and Imagined movements with Eyes Free or with Eyes Motionless.
      The first result was a facilitation effect of saccades upon both executed and
      imagined arm movements as revealed by the shorter arm movement durations in Eyes
      Free than in Eyes Motionless. Another interesting finding was that executed and
      imagined movements preserved their temporal similarities in both Eyes Free and
      Eyes Motionless, suggesting that the accuracy of motor representations is not
      dependent on the presence or lack of eye movements. This result and the close
      similarities between the EOG patterns accompanying both executed and imagined arm
      pointing movements in Eyes Free, argue in favour of a similar neurocognitive
      network in executed and imagined actions. We propose that internal forward models
      provide fine estimations of the temporal features of imagined arm movements,
      whatever they accompanied, or not, by orientation saccades.

PMID- 18035338
TI  - Calcitonin gene-related peptide dynamics in rat dorsal root ganglia and spinal
      cord following different sciatic nerve injuries.
AB  - We examined calcitonin gene-related peptide (CGRP) expression dynamics in the
      dorsal root ganglia (DRGs) and spinal cords of adult rats subjected to one of the
      following three types of unilateral sciatic nerve injury: crush (SNC), ligation
      (SNL), or transection combined with subsequent neurorrhaphy (SNT). Following SNC,
      CGRP immunoreactivity (IR) was increased in ipsilateral primary sensory neurons
      of L4-L5 DRGs, laminae I-II and spinal motoneurons; an area of CGRP-labeled
      fibers in ipsilateral laminae III-V was also increased in size following SNC.
      CGRP up-regulation exhibited a distinct temporospatial pattern and expression
      levels had returned to baseline levels by the end of the 28-day test period.
      Similar to SNC, SNT also resulted in an increase of CGRP-IR in these areas,
      though to a slightly lesser degree in the three latter areas. By contrast SNL,
      which is associated with complete blockade of axonal transport, induced a
      sustained decrease in CGRP-IR in primary sensory neurons of L4-L5 DRGs and
      superficial laminae (I-IIo), as well as in an ipsilateral area occupied by CGRP
      labeled fibers. Interestingly, SNL did not affect CGRP-IR in spinal motoneurons,
      but did result in an accumulation of nerve growth factor (NGF) distal to ligature
      that was apparent as early as 1 day post-injury and persisted throughout the
      experimental period. These findings indicate that the nature of peripheral nerve
      injury has an impact on CGRP expression dynamics and that the response involves
      target tissues in vivo. Our results have important implications for elucidating
      the mechanisms of nerve regeneration.

PMID- 18035339
TI  - Comparison of event-related potentials in attentional blink and repetition
      blindness.
AB  - Attending to the first target in rapid serial visual presentation (RSVP)
      interferes with processing of the second target so that the participants fail to
      recognize the second target if the targets are separated by a stimulus onset
      asynchrony of 200-500 ms. This phenomenon is attentional blink (AB). Repetition
      blindness (RB) is an additional difficulty to recognize the second occurrence of
      the same stimulus in RSVP. A controversial issue in studies of both deficits is
      the processing level at which they occur. To compare the timing and mechanisms of
      AB and RB directly during the same RSVP stream, we recorded event-related
      potentials (ERPs) in response to repeated and unrepeated targets. Comparable to
      earlier ERP studies on visual awareness, the results showed for both types of
      targets a negative amplitude difference between ERPs to consciously recognized
      and unrecognized targets during 250-350 ms from stimulus onset, suggesting that
      both AB and RB are associated with deficits of conscious perception, occurring at
      earlier stages than access to working memory. However, the perceptual deficit in
      RB is more severe, which may be related to higher overall negativity in response
      to repeated targets observed 150-300 ms after stimulus onset, suggesting stronger
      cortical baseline activation and higher perceptual threshold for repeated targets
      as compared with unrepeated ones.

PMID- 18035340
TI  - CA1 ischemic injury does not affect the ability of Mongolian gerbils to solve
      response, direction, or place problems.
AB  - Open field and T-maze paradigms are used to test the effects of hippocampal
      lesions on spatial memory in rodents. Place cells in the dorsal CA1 region of the
      hippocampus are known to be responsible for the formation of global place maps,
      while CA3 neurons respond to changes in local contexts. It is proposed here that
      when dorsal CA1 is selectively destroyed, gerbils will be unable to solve
      direction and place problems while context-dependent representations of relative
      maze positions should be spared since CA3 cells are left intact. Twenty female
      Mongolian gerbils were subjected to 5 min of forebrain ischemia, and, along with
      20 controls, were subsequently tested on a response, direction or one of two
      types of open field place problems. Locomotion in a circular open field was
      recorded as a measure of hyperactivity. Gerbils with damage restricted to dorsal
      CA1 were hyperactive compared to controls, but were not impaired on place,
      direction, or response tasks. Because gerbils solved these tasks in the absence
      of dorsal CA1, maze tasks which have traditionally been labeled "place" or
      "direction" tasks may actually be testing the animal's ability to discriminate
      between two relative contexts, without the need for a global place map. Our
      findings support recent reports that different hippocampal subfields control
      different aspects of spatial learning and memory. Specifically, the context
      dependent representations in CA3 appear to support the learning of the "place"
      and, likely, "direction" solutions in current and previous open field and T-maze
      tasks.

PMID- 18035341
TI  - Preparation and spectroscopic characterization of methoxy poly(ethylene glycol)
      grafted water-soluble chitosan.
AB  - The object of this study was to test the solubility of a methoxy poly(ethylene
      glycol) (MPEG)-grafted chitosan copolymer in organic solvents and aqueous
      solution. Water-soluble chitosan with low molecular weight (LMWSC) was used in a
      PEG-graft copolymerization. The MPEG was conjugated to chitosan using 4
      dicyclohexylcarbodimide (DCC), and N-hydroxysuccimide (NHS). Introduction of PEG
      was confirmed by (1)H and (13)C NMR spectroscopy and FT-IR spectroscopy. The
      degree of substitution (DS) of MPEG into chitosan was calculated from (1)H NMR
      data and also by estimating the molecular weight (MW) using gel permeation
      chromatography (GPC). The DS values obtained from (1)H NMR spectroscopy and GPC
      were similar, indicating that MPEG-grafted LMWSC was synthesized and properly
      characterized. Furthermore, the introduction of PEG into chitosan increases the
      solubility in aqueous solutions over a range of pH values (4.0-11.0) and organic
      solvents such as DMF, DMSO, ethanol, and acetone.

PMID- 18035342
TI  - Preparation and metal-binding behaviour of chitosan functionalized by ester- and
      amino-terminated hyperbranched polyamidoamine polymers.
AB  - A series of insoluble chitosan (CTS) derivatives were prepared by grafting ester-
      and amino-terminated dendrimer-like polyamidoamine (PAMAM) into CTS using a
      divergent method by repeating two processes: (1) Michael addition of methyl
      acrylate (MA) to surface amino groups, and (2) amidation of the resulting esters
      with ethylenediamine (EDA). Their structures were characterized by infrared
      spectra (IR) and wide-angle X-ray diffraction (WAXD). The adsorption capabilities
      of the products for Au(3+), Pd(2+), Pt(4+), Ag(+), Cu(2+), Zn(2+), Hg(2+),
      Ni(2+), and Cd(2+) were studied. The results showed that the products exhibited
      better adsorption capabilities for Au(3+) and Hg(2+) than for other metal ions,
      and the adsorption capabilities of amino-terminated products were higher than
      those of ester-terminated ones. Also it was observed that a high percentage of
      grafting of PAMAM into CTS does not ensure a high adsorption capacity.

PMID- 18035343
TI  - Molecular structures of glycal-based bolaamphiphiles: analysis of crystal packing
      and hydrogen-bond networks.
AB  - The crystal structures for the glycal bolaamphiphiles, 1,12-bis-(2,3-alpha-D
      erythro-hex-2-enopyranosyloxy)-dodecane (1) and 1,12-bis-(2,3-alpha-D-threo-hex-2
      enopyranosyloxy)-dodecane (2), were determined by single-crystal X-ray analysis.
      The structure for 1 showed that the alpha:alpha and alpha:beta diastereomers co
      crystallized, with occupancy factors determining an isomeric ratio of 69:31. The
      pyranose rings for both structures are oriented away from each other and adopt a
      conventional glycal geometry. The head groups are nearly gauche to the
      hydrophobic chain, which adopts an all-trans zigzag conformation. Bolaamphiphile
      1 packs in anti-parallel layers, while bolaamphiphile 2 displays a parallel
      arrangement of layers. Both structures display a three-dimensional hydrogen
      bonding network involving the hydroxylic substituents on the head groups. The
      high similarity in large-scale solid state structures between 1 and glucosamide
      bolaamphiphile 3, and 2 and galactosamide bolaamphiphile 4 suggest a strong
      dependence on head group stereochemistry, and that only a few, key intermolecular
      interactions between head groups are necessary in controlling the ultimate
      structure observed. The solid state results may have implications for
      understanding the intermolecular forces directing nanoscale self-assembly in
      solution.

PMID- 18035344
TI  - Zinc protoporphyrin levels, blood lead levels and neurocognitive deficits in
      Andean children with chronic lead exposure.
AB  - OBJECTIVES: To investigate the relationship between blood lead (PbB), zinc
      protoporphyrin (ZPP) levels and performance on a test of auditory memory in
      Andean children and adolescents with chronic lead (Pb) exposure. DESIGN AND
      METHODS: PbB and ZPP levels were measured in blood samples from 166 participants
      (aged 6-16 yrs.) exposed to Pb in a local ceramic glazing cottage industry in
      Ecuadorian villages. PbB levels and ZPP/heme ratios were analyzed in relation to
      performance on the Digit Span subtest of the Wechsler IV intelligence scale, a
      test of auditory memory. RESULTS: Mean PbB level for the study group was 18.0
      microg/dL (S.D.: 15.1; range: 3.0-86.0), and the mean ZPP/heme ratio was 105.7
      mumol/mol (S.D.: 100.9; range: 36.0-592.0). There was no significant difference
      in PbB and ZPP levels between the 84 females and the 82 males. The mean Digit
      Span scale score (DS SS) for the study group was 6.81 (S.D.: 2.95; range: 1.0
      17.0), which is below the average score of 10 for the test, with the females
      performing significantly better than males (t=2.435; p=0.01). Regression analyses
      revealed statistically significant inverse associations between DS SS and PbB
      level (r=0.251, p=0.001), and between DS SS and ZPP/heme ratio (r=0.246,
      p=0.001). CONCLUSION: Elevated PbB levels, representing acute exposure, and ZPP
      levels, reflecting chronic Pb exposure in this cohort of Andean inhabitants were
      associated with poor performance on a test of auditory memory, suggesting that
      the children and adolescents in the study area have neurocognitive deficits that
      may affect learning.

PMID- 18035345
TI  - National Academy of Clinical Biochemistry and IFCC Committee for Standardization
      of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: analytical
      issues for biomarkers of heart failure.

PMID- 18035346
TI  - Segmenting dynamic human action via statistical structure.
AB  - Human social, cognitive, and linguistic functioning depends on skills for rapidly
      processing action. Identifying distinct acts within the dynamic motion flow is
      one basic component of action processing; for example, skill at segmenting action
      is foundational to action categorization, verb learning, and comprehension of
      novel action sequences. Yet little is currently known about mechanisms that may
      subserve action segmentation. The present research documents that adults can
      register statistical regularities providing clues to action segmentation. This
      finding provides new evidence that structural knowledge gained by mechanisms such
      as statistical learning can play a role in action segmentation, and highlights a
      striking parallel between processing of action and processing in other domains,
      such as language.

PMID- 18035347
TI  - Tbx6, Thylacine1, and E47 synergistically activate bowline expression in Xenopus
      somitogenesis.
AB  - T-box factor, Tbx6, is a prerequisite for somite segmentation in vertebrates. We
      recently identified a negative regulator of Tbx6, Bowline, which represses the
      expression of genes involved in somite segmentation by suppressing the
      transcriptional activity of Tbx6. According to this function, bowline gene
      expression is restricted to the most anterior presomitic mesoderm where the
      somite segmentation program terminates, although it remains unclear how bowline
      expression is activated. To address this, we investigated the cis-regulatory
      region of bowline. Measuring luciferase activity driven by the bowline promoter,
      we found that Tbx6, Thylacine1, and E47 synergistically activate bowline
      expression in vitro. We also found that Tbx6, Thylacine1, and E47 are
      spatiotemporally sufficient to induce bowline expression in Xenopus
      somitogenesis. Our findings indicated that besides being a negative regulator of
      Tbx6, bowline itself is also regulated by Tbx6, suggesting the negative feedback
      loop of Tbx6-Bowline in the termination step of somite segmentation.

PMID- 18035348
TI  - Group III metabotropic glutamate receptors act as hetero-receptors modulating
      evoked GABA release in the globus pallidus in vivo.
AB  - In vitro studies suggest that group III metabotropic glutamate (mGlu) receptors
      function as hetero-receptors to modulate GABA release within the globus pallidus.
      In the present study we examined this hypothesis in vivo, using microdialysis to
      assess the ability of locally infused group III mGlu receptor agonists to
      modulate KCl-evoked GABA release in the globus pallidus of anaesthetised rats.
      Extra-cellular levels of GABA in dialysate samples were assayed using High
      Pressure Liquid Chromatography (HPLC) coupled to electrochemical detection.
      Infusion of KCl (50-100 mM) evoked a dose-dependent increase in GABA levels in
      the globus pallidus. Addition of the group III mGlu receptor agonists l-AP4 (30
      and 300 microM) and l-SOP (3-300 microM) significantly reduced the extra-synaptic
      levels of GABA that resulted after 100 mM KCl challenge. The effect of L-SOP (30
      microM) was almost totally abolished by co-infusion with M-SOP (30 microM). These
      data confirm that activation of group III mGlu receptors inhibits GABA release in
      the globus pallidus, thereby supporting their hetero-receptor role in vivo.

PMID- 18035349
TI  - Pedicularioside A from Buddleia lindleyana inhibits cell death induced by 1
      methyl-4-phenylpyridinium ions (MPP+) in primary cultures of rat mesencephalic
      neurons.
AB  - Parkinson's disease is characterized by the progressive degeneration of midbrain
      dopaminergic neurons. Buddleia lindleyana is a traditional Chinese herb, commonly
      called Zui Yu Cao. The purification and identification of pedicularioside A and
      other phenylethanoid glycosides from this plant have been reported. However,
      their neuroprotective effects on the 1-methyl-4-phenylpyridinium ion (MPP(+))
      induced death of rat mesencephalic neuron primary cultures and the precise
      mechanism of this protection remains unclear. We used the 3-(4, 5-dimethylthiozol
      2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay for cellular growth to examine
      the effects of five phenylethanoid glycosides isolated from B. lindleyana,
      including pedicularioside A, leucosceptoside A, isoacteoside, acteoside, and
      arenariside, on the viability of mesencephalic neurons treated with MPP(+). Of
      the compounds tested, pedicularioside A exhibited the greatest degree of
      protection from MPP(+)-induced cell death. We also observed a marked increase in
      the number of tyrosine hydroxylase immunoreactive neurons. Pedicularioside A
      inhibited expression of the caspase-3 gene and cleavage of poly (ADP-ribose)
      polymerase (PARP) in cultures exposed to MPP(+). Our results suggest that
      pedicularioside A has a neuroprotective effect to improve the survival of
      mesencephalic neurons (dopaminergic neurons and non-dopaminergic neurons). The
      mode of action appears to be the inhibition of caspase-3 gene expression, thereby
      protecting mesencephalic neurons from MPP(+)-induced cell death.

PMID- 18035350
TI  - GABAA receptor pharmacology of fluorinated derivatives of the novel sedative
      hypnotic pyrazolopyrimidine indiplon.
AB  - The function of gamma-aminobutyric acid type A receptors (GABA(A) receptors) is
      enhanced by various clinically important drugs including benzodiazepines that act
      on an allosteric site formed at the interface between the alpha and gamma
      subunits. In contrast to classical benzodiazepines, the novel pyrazolopyrimidine
      indiplon (N-methyl-N-{3-[7-(thiophene-2-carbonyl)-1,5,9-triazabicyclo[4.3.0]nona
      2,4,6,8-tetraen-2-yl]phenyl}acetamide; N-methyl-N-{3-[3-(thiophene-2-carbonyl)
      pyrazolo[1,5-a]pyrimidine-7-yl]phenyl}-acetamide) demonstrates relative binding
      selectivity for the alpha1 subunit containing receptor subtypes, which are the
      most frequently expressed in the mammalian central nervous system. To investigate
      the pharmacological properties at GABA(A) receptors and to promote the
      development of alpha1 subunit selective radiotracers for positron emission
      tomography imaging, we have started with the evaluation of various fluorinated
      indiplon derivatives. Binding affinities were determined in homogenates from
      newborn and adult rats suggesting an alpha1 preference of the reference compounds
      indiplon, zaleplon as well as for all newly synthesized indiplon derivatives. In
      homogenated cerebellar tissue obtained from adult rat brain, known to primarily
      express alpha1 containing GABA(A) receptors, the high affinity of the basic
      indiplon structure was only slightly affected by an elongation of the alkyl
      substituent of the amide N from methyl (indiplon; K(i) 3.1 nM) via ethyl (2a, N
      (2-fluoro-ethyl)-N-{3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidine-7
      yl]phenyl}-acetamide; K(i) 5.4 nM) to propyl (2b, N-(3-fluoro-propyl)-N-{3-[3
      (thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidine-7-yl]phenyl}-acetamide; K(i) 2.4
      nM). Whole cell patch-clamp recordings at neuronal and recombinant GABA(A)
      receptors indicated that the fluorinated derivatives 2a and 2b have a high
      potency at alpha1beta3gamma2L isoforms comparable to indiplon (EC(50): 105, 158,
      and 81 nM, respectively), with 2b displaying the most pronounced efficacy at
      alpha3beta3gamma2L subtypes. In conclusion, the affinity profiles and functional
      properties of the newly synthesised fluorinated indiplon derivatives make
      compounds 2a and 2b suitable for the development of [(18)F]-labelled ligands at
      GABA(A) receptors containing the alpha1 subunit.

PMID- 18035351
TI  - 5-hydroxytryptamine1B receptor and triptan response in migraine, lack of
      association with common polymorphisms.
AB  - Triptans mediate vasoconstriction of meningeal vessels via stimulation of
      vascular 5-hydroxytryptamine (5-HT)(1B) receptors. These drugs are recommended
      for acute treatment in patients with moderate-to-severe migraine attacks and in
      those patients with mild-to-moderate headache that are not controlled adequately
      by other agents. Yet, approximately 25% of all migraine users and 40% of all
      attacks do not respond to triptan treatment. Among the hypothesis to explain this
      is the possibility that genetic single nucleotide polymorphisms that alter the
      receptor, for example changing the transcriptional rate and therefore the amount
      of target protein might change the clinical response to these drugs. In the
      present contribution, we therefore decided to evaluate whether single nucleotide
      polymorphisms on the 5-HT(1B) gene might contribute to inter-individual
      variability in clinical responses to triptans. Two polymorphisms in the promoter
      region of the 5-HT(1B) receptor (T-261G and A-161T) and the synonymous variation
      G861C in the coding region were genotyped by restriction fragment length
      polymorphism in 105 migraine patients. In our sample population, 71% of patients
      responded to triptans. Allelic and diplotype frequencies were not significantly
      different between responders and non-responders. On the other hand, extrapolation
      of in vitro data on promoter activity would suggest that patients with higher
      copy number of receptors respond slightly better. Our data therefore do not
      support the involvement of 5-HT(1B) single nucleotide polymorphisms in mediating
      the inter-individual variability to triptans.

PMID- 18035352
TI  - Expression of Kir7.1 and a novel Kir7.1 splice variant in native human retinal
      pigment epithelium.
AB  - Previous studies on bovine retinal pigment epithelium (RPE) established that
      Kir7.1 channels compose this epithelium's large apical membrane K+ conductance.
      The purpose of this study was to determine whether Kir7.1 and potential Kir7.1
      splice variants are expressed in native adult human RPE and, if so, to determine
      their function and how they are generated. RT-PCR analysis indicated that human
      RPE expresses full-length Kir7.1 and a novel Kir7.1 splice variant, designated
      Kir7.1S. Analysis of the human Kir7.1 gene (KCNJ13) organization revealed that it
      contains three exons, two introns, and a novel alternative 5' splice site in exon
      2. In human RPE, the alternative usage of two competing 5' splice sites in exon 2
      gives rise to transcripts encoding full-length Kir7.1 and Kir7.1S, which is
      predicted to encode a truncated protein. Real-time PCR indicated that Kir7.1
      transcript is nearly as abundant as GAPDH mRNA in human RPE whereas Kir7.1S
      transcript expression is 4-fold lower. Western blot analysis showed that the
      splice variant is translated in Xenopus oocytes injected with Kir7.1S cRNA and
      revealed the expression of full-length Kir7.1 but not Kir7.1S in adult human RPE.
      Co-expression of Kir7.1 with Kir7.1S in Xenopus oocytes had no effect on either
      the kinetics or amplitude of Kir7.1 currents. This study confirms the expression
      of Kir7.1 in human RPE, identifies a Kir7.1 splice variant resulting in predicted
      changes in protein sequence, and indicates that there is no functional
      interaction between this splice variant and full-length Kir7.1.

PMID- 18035353
TI  - Gazing into the future: Parkinson's disease gene therapeutics to modify natural
      history.
AB  - PD gene therapy clinical trials have primarily focused on increasing the
      production of dopamine (DA) through supplemental amino acid decarboxylase (AADC)
      expression, neurotrophic support for surviving dopaminergic neurons (DAN) or
      altering brain circuitry to compensate for DA neuron loss. The future of PD gene
      therapy will depend upon resolving a number of important issues that are
      discussed in this special issue. Of particular importance is the identification
      of novel targets that are amenable to early intervention prior to the substantial
      loss of DAN. However, for the most part the etiopathogenesis of PD is unknown
      making early intervention a challenge and the development of early biomarker
      diagnostics imperative.

PMID- 18035354
TI  - Neurosteroid dehydroepiandrosterone sulphate inhibits persistent sodium currents
      in rat medial prefrontal cortex via activation of sigma-1 receptors.
AB  - Dehydroepiandrosterone sulphate is one of the most important neurosteroids. In
      the present paper, we studied the effect of dehydroepiandrosterone sulphate on
      persistent sodium currents and its mechanism and functional consequence with
      whole-cell patch clamp recording method combined with a pharmacological approach
      in the rat medial prefrontal cortex slices. The results showed that
      dehydroepiandrosterone sulphate inhibited the amplitude of persistent sodium
      currents and the inhibitory effect was significant at 0.1 microM, reached maximum
      at 1 microM and decreased with the increase in the concentrations of above 1
      microM. The effect of dehydroepiandrosterone sulphate on persistent sodium
      currents was canceled by the Gi protein inhibitor and the protein kinase C
      inhibitor, but not by the protein kinase A inhibitor. The effect of
      dehydroepiandrosterone sulphate on persistent sodium currents was also canceled
      by the sigma-1 receptor blockers and the sigma-1 receptor agonist could mimic the
      effect of dehydroepiandrosterone sulphate. Dehydroepiandrosterone sulphate had no
      significant influence on neuronal excitability but could significantly inhibit
      chemical inhibition of mitochondria-evoked increase in persistent sodium
      currents. These results suggest that dehydroepiandrosterone sulphate inhibits
      persistent sodium currents via the activation of sigma-1 receptors-Gi protein
      protein kinase C-coupled signaling pathway, and the main functional consequence
      of this effect of DHEAS is presumably to protect neurons under ischemia.

PMID- 18035356
TI  - Topical imiquimod therapy for external anogenital warts in pregnant women.

PMID- 18035355
TI  - Behavioral and biological effects of chronic S18986, a positive AMPA receptor
      modulator, during aging.
AB  - AMPA receptors are a major subtype of ionotropic receptors that respond to
      glutamate. Positive allosteric modulators of AMPA receptors selectively enhance
      fast excitatory neurotransmission in the brain and increase overall neuronal
      excitability. In addition to enhancing cognitive performance, S18986 (Servier,
      France) and other AMPA receptor modulators have also been shown to be
      neuroprotective. A particularly relevant context for AMPAR modulator studies is
      during aging because of increased neuronal vulnerability. It is currently unknown
      if chronic AMPAR modulator treatment can alter the course of brain aging, a
      process characterized by impairment of cognitive function, reduced neuronal
      excitability, and increased inflammation in the brain. We examined the behavioral
      and some relevant CNS effects of chronic S18986 in rats from 14 to 18 months of
      age. Here we show that chronic, oral administration of S18986 increases locomotor
      activity and performance in a spatial memory task in aged rodents. In addition,
      chronic S18986 treatment retards the decline of forebrain cholinergic neurons by
      roughly 37% and midbrain dopaminergic neurons by as much as 43% during aging and
      attenuates the age-related increase in the expression of a microglial marker in
      the hippocampus. These results provide a framework for further studies of the
      potentially beneficial effects of AMPAR modulators on brain aging.

PMID- 18035358
TI  - Matrix solid-phase dispersion extraction versus solid-phase extraction in the
      analysis of combined residues of hexachlorocyclohexane isomers in plant matrices.
AB  - This paper describes a method based on matrix solid-phase dispersion (MSPD) to
      determine the presence of combined residues of hexachlorocyclohexane (HCH)
      isomers (alpha-, beta-, gamma- and delta-) in various plant matrices including
      vegetables, fruits, leaves, grains and roots, by gas chromatography with (63)Ni
      electron-capture detection. The MSPD method consists of sample homogenization,
      cellular disruption, exhaustive extraction, fractionation and clean up by simple
      processes in which a small amount of sample (5 g) was blended with Florisil and
      the mixture passed into a small chromatographic column and eluted with 10 ml of n
      hexane-ethyl acetate solvent mixture (70:30; v/v) and repeated with another 10 ml
      of the same solvent mixture. A comparison with classical solid-phase extraction
      (SPE) showed MSPD to be efficient, fast, simple and easy to perform. The
      detection limit of various HCH isomers was found to be in the range of 2.15-5.68
      ng and method detection limit varied from 0.465 to 1.136 ng g(-1). Mean
      recoveries were found in the range of 91-98%. Till date, there are no official
      methods or standards by Central Pollution Control Board or Bureau of Indian
      standards that take into account India's real life conditions in the analysis of
      pesticide residues in plant matrices and the MSPD method described herein has
      proved to be a feasible one for the analysis of combined residues of HCH isomers
      in various plant materials.

PMID- 18035357
TI  - Tudor domain proteins in protozoan parasites and characterization of Plasmodium
      falciparum tudor staphylococcal nuclease.
AB  - RNA-binding proteins play key roles in post-transcriptional regulation of gene
      expression. In eukaryotic cells, a multitude of RNA-binding proteins with several
      RNA-binding domains/motifs have been described. Here, we show the existence of
      two Tudor domain containing proteins, a survival of motor neuron (SMN)-like
      protein and a Staphylococcus aureus nuclease homologue referred to as TSN, in
      Plasmodium and other protozoan parasites. Activity analysis shows that Plasmodium
      falciparum TSN (PfTSN) possesses nuclease activity and Tudor domain is the RNA
      binding domain. A specific inhibitor of micrococcal nucleases, 3',5'
      deoxythymidine bisphosphate (pdTp) inhibits the nuclease as well as RNA-binding
      activities of the protein. PfTSN shows a predominant nuclear localization.
      Treatment of P. falciparum with pdTp, inhibited in vitro growth of both
      chloroquine-sensitive and chloroquine-resistant strains of P. falciparum, while a
      four fold concentration of pdTp did not have any significant effect on the
      mammalian cell line, Huh-7D12. Altogether, these results suggest that PfTSN is an
      essential enzyme in the parasite's life cycle.

PMID- 18035359
TI  - Accelerated purification process development of monoclonal antibodies for
      shortening time to clinic. Design and case study of chromatography processes.
AB  - For accelerating the purification process development of human monoclonal
      antibodies (hmAbs) for pharmaceutical drugs, we designed a standardized method
      for setting the conditions of the purification process, which could be applied to
      hmAbs for the early phase of pharmaceutical development. The process includes
      three sequential chromatography steps: Protein A affinity chromatography (AFC),
      anion-exchange chromatography (AIEC) and cation-exchange chromatography (CIEC),
      and also includes a low pH virus inactivation step after the AFC step. We
      predicted the elution pH in the AFC and elution salt concentration in the CIEC
      from the amino acid sequences of hmAbs, as described in our previous paper. The
      mobile phase pH in AIEC and the pH for virus inactivation were also predicted
      based on the amino acid sequence of hmAb. As a case study, six hmAbs (two of
      IgG(1), two of IgG(2) and two of IgG(4)) were purified with the standardized
      method. The recovery, purity and clearance of impurities (DNA, host cell proteins
      (HCP), and Protein A) were examined. All the six hmAbs were purified with high
      recovery and high clearance of the impurities. Factors affecting the impurities
      level in the purified products are also discussed.

PMID- 18035360
TI  - Trace level determination of beta-blockers in waste waters by highly selective
      molecularly imprinted polymers extraction followed by liquid chromatography
      quadrupole-linear ion trap mass spectrometry.
AB  - This paper describes the development of an analytical methodology to determine
      eight beta-blockers in waste waters using molecularly imprinted polymers (MIPs)
      as extraction and pre-concentration material, followed by liquid chromatography
      quadrupole-linear ion trap mass spectrometry (LC-QqLIT MS). The advantages
      offered by MIPs, in terms of selectivity and specificity, were compared with the
      most commonly polymeric materials used (the lipophilic-hydrophilic balanced Oasis
      HLB cartridges). Even though recoveries achieved with both sorbents were similar,
      ranging from 50 to 110% for sewage treatment plant (STP) effluent and 40-110 for
      STP influent, respectively, MIPs provided lower method detection limits than
      Oasis HLB, due to their specificity for target analytes and closely related
      analogues. Method detection limits (MDL) achieved using MIPs ranged from 0.2 to
      6.4 ng/L for STP effluent and from 0.4 to 6.5 ng/L for STP influent. To highlight
      the advantages of MIPs against conventional polymeric cartridges, a detailed
      matrix effects study as well as cross reactivity tests were performed. For the
      latter purpose, the extraction efficiency of some pharmaceuticals and pesticides
      belonging to different therapeutic classes was assessed. LC-QqLIT MS, used for
      quantification and confirmation, proved to be a powerful analytical tool, as
      instrumental detection limits (IDL) achieved ranged from 0.2 to 2.7 pg injected
      (in multiple reaction monitoring mode (MRM)). In addition the inclusion of high
      sensitive MS/MS scans for each compound when working in Information Dependent
      Acquisition mode (IDA) provided extra confirmation for unequivocal identification
      of target compounds in complex environmental matrices.

PMID- 18035361
TI  - Characterization of monomeric and oligomeric flavan-3-ols from barley and malt by
      liquid chromatography-ultraviolet detection-electrospray ionization mass
      spectrometry.
AB  - The pattern of the monomeric and oligomeric flavan-3-ols for 10 barley varieties
      and the corresponding malts were identified and quantified using high-performance
      liquid chromatography-ultraviolet detection-electrospray ion trap mass
      spectrometry. The Folin-Ciocalteau and the vanillin spectrophotometric assays
      were used for the assessment of the total polyphenol and total flavan-3-ol
      content, respectively, and the antioxidant activity was determined as the 2,2
      diphenyl-1-picrylhydrazyl radical scavenging activity and the ferricyanide
      reducing power. Catechin and prodelphinidin B3 were respectively the major
      monomeric and dimeric flavan-3-ols. Moreover, prodelphinidin B3 was shown to be
      the main contributor for the radical scavenging activity both for barley and
      malt.

PMID- 18035362
TI  - Gas chromatographic high-throughput screening techniques in catalysis.
AB  - Discovering highly efficient catalysts is of great scientific and economical
      interest. Advances in high-throughput assays in combination with sophisticated
      analytical techniques have increased the rapidity with which catalysts can be
      identified and optimized. Understanding how kinetics in the mechanism of
      catalysis is controlled by structural parameters is essential for a directed
      design of catalysts. To identify such rate-controlling elementary steps and to
      develop and refine models, comprehensive experimental kinetic data of a broad
      variety of substrates are necessary. In the present article concepts of high
      throughput screening techniques in catalysis using gas chromatography are
      reviewed in a survey covering the period from 1998 to 2007. To cover also the
      origins of concepts and groundbreaking experiments in this research area
      milestones going back to 1950 are also reviewed. The first part of the review
      will focus on off-line gas chromatographic analysis, the second part on on-line
      gas chromatographic analysis covering sequential, parallelized and high
      throughput multiplexing gas chromatography. The third part presents recent
      advances in the integration of chemical transformation and analysis in gas
      chromatography. The present review article describes the state-of-the-art, scope
      and limitations, and applications of these different high-throughput screening
      approaches.

PMID- 18035363
TI  - Metabolism and toxicological detection of a new designer drug, N-(1
      phenylcyclohexyl)propanamine, in rat urine using gas chromatography-mass
      spectrometry.
AB  - Studies are described on the metabolism and the toxicological detection of the
      phencyclidine-derived designer drug N-(1-phenylcyclohexyl)-propanamine (PCPR) in
      rat urine using gas chromatographic-mass spectrometric techniques. The identified
      metabolites indicated that PCPR was metabolized by hydroxylation of the
      cyclohexyl ring at different positions, hydroxylation of the phenyl ring, N
      dealkylation, and combinations of these steps. Parts of the metabolites were
      excreted in conjugated form. The authors' systematic toxicological analysis (STA)
      procedure using full-scan GC-MS after acid hydrolysis, liquid-liquid extraction
      and microwave-assisted acetylation allowed the detection of an intake of a common
      drug users' dose of PCPR in rat urine. Assuming similar metabolism in humans, the
      STA should be suitable for proof of an intake of PCPR in human urine.

PMID- 18035364
TI  - On-line sample preconcentration in capillary electrophoresis. Fundamentals and
      applications.
AB  - On-line preconcentration is one of the aspects of analytical method development
      using capillary electrophoretic techniques. The choice of the sample matrix alone
      can significantly alter both method sensitivity and separation efficiency. The
      recent trend to detect samples in narrower separation vessels also necessitates
      the need to improve detection sensitivity. The desire to detect very low levels
      of analytes using limited amounts of sample from biological specimens and the
      high separation efficiency obtainable using very large injections compared to
      classical small size injections also adds to this list. Indeed, one of the rich
      areas of research in the capillary electrophoresis field is on on-line sample
      preconcentration. More than 400 published research articles gathered from the
      http://www.webofscience.com from the year 2000 described a form of on-line
      preconcentration in capillary electrophoresis. This review provides a
      comprehensive table listing the applications of on-line preconcentration in
      capillary electrophoresis.

PMID- 18035365
TI  - On-line enantiomeric analysis using high-performance liquid chromatography in
      chiral separation by simulated moving bed.
AB  - An automated on-line enantiomeric analysis system comprising an analytical HPLC
      set-up with two UV detectors sharing the same light source has been employed to
      monitor the internal composition profile in chiral simulated moving bed
      chromatography. This monitoring scheme does not use a polarimeter. Using a
      sampling interface placed between two SMB columns, effluent samples are directed
      onto a high-efficiency analytical column at a sampling rate faster than the
      overall dynamics of the preparative unit to achieve on-line enantiomeric analysis
      of the composition profile. The other UV detector is placed in the SMB loop
      before the fraction collector to provide instantaneous measurement of the total
      enantiomeric concentration. The feasibility and effectiveness of the on-line
      enantiomeric monitoring scheme were assessed experimentally on the separation of
      Troger's base racemate, using Chiralpak AD as stationary phase and methanol as
      eluent. It was found that robust monitoring of the concentration profiles of the
      individual enantiomers is best achieved when the enantiomeric purity obtained
      from the peak areas of the on-line enantiomer analysis chromatograms is combined
      with the on-line UV measurement of total enantiomeric concentration. The accuracy
      and robustness of the proposed on-line enantiomeric monitoring system open up
      promising perspectives for process control and dynamic optimization of the SMB.

PMID- 18035367
TI  - High-performance liquid chromatography with contactless conductivity detection
      for the determination of peptides and proteins using a monolithic capillary
      column.
AB  - Gradient programs were applied to the determination of peptides and proteins in
      HPLC with contactless conductivity detection. A monolithic capillary column was
      used for the fast and sensitive determination of the biochemical species in
      acidic mobile phases consisting of acetic acid or trifluoroacetic acid in various
      concentrations of acetonitrile in water. The drift in baseline, which is caused
      by conductivity changes during the elution program, was minimized by careful
      optimization of the composition of the mobile phase and remaining drift was
      removed by computational baseline normalization. The flow rate from a
      conventional HPLC pump was reduced to a flow rate suitable for capillary systems
      using a pre-column flow splitter and a final total flow rate of 1.65 microl/min
      was used for all capillary HPLC separations. The contactless conductivity
      detector was positioned directly on the outlet capillary of the separation column
      and positively charged peptides and proteins were determined as sharp and
      symmetrical peaks. Detection limits in a concentration range from 3.7 x 10(-8) to
      5.1 x 10(-7)M and a reproducibility of peak areas and peak heights between 2.3%
      and 7.3% were achieved for all biochemical species tested.

PMID- 18035366
TI  - High-throughput solid-phase extraction of metal ions using an iminodiacetate
      chelating porous disk prepared by graft polymerization.
AB  - A chelating porous sheet for use in solid-phase extraction was prepared by
      radiation-induced graft polymerization and subsequent chemical modifications. An
      epoxy-group-containing vinyl monomer was graft-polymerized onto a porous sheet
      made of polyethylene. The produced epoxy group of the graft chain was converted
      into an iminodiacetate group. The chelating porous sheet with a density of the
      iminodiacetate group of 2.1 mol/kg was cut into disks 13 mm in diameter to fit an
      empty cylindrical cartridge with a capacity of 6 mL. Breakthrough curves using
      the chelating-porous-disk-packed cartridge overlapped irrespective of the flow
      rate of the solution ranging up to 1500 mL/h because of negligible diffusional
      mass-transfer resistance of the copper ions to the iminodiacetate group of the
      graft chain.

PMID- 18035368
TI  - Preparation, characterization, and photocatalytic activity of sulfate-modified
      titania for degradation of methyl orange under visible light.
AB  - Hydrated titania was prepared by a sol-gel method, taking tetraisopropyl
      orthotitanate as starting material, and then promoted with different weight
      percentages of sulfate by an incipient wetness impregnation method. The materials
      were characterized by various advanced techniques such as PXRD, BET surface area,
      N(2) adsorption-desorption measurements, FTIR, and SEM. Analytical results
      demonstrated that TiO(2) is mesoporous in nature, and sulfate modification could
      inhibit the phase transformation and enhance the thermal stability of TiO(2). It
      was also found that sulfate modification could reduce the crystallite size and
      increase the specific surface area of the catalysts. The degradation of methyl
      orange under solar radiation was investigated to evaluate the photocatalytic
      activity of these materials. Effects of different parameters such as pH of the
      solution, amount of catalyst, additives, and kinetics were investigated. At 2.5
      wt% sulfate loading, the average percentage of degradation of methyl orange was
      nearly two times than that of neat TiO(2). The photocatalytic degradation
      followed first-order kinetics.

PMID- 18035369
TI  - Molecular features of the air/carbonate solution interface.
AB  - The nature of the air/carbonate solution interface is considered with respect to
      water structure by sum-frequency vibrational spectroscopy (SFVS) and molecular
      dynamics simulations (MDS). Results from this study provide further understating
      regarding previous observations that the surface tensions of structure making
      sodium carbonate solutions have been shown to be significantly greater than the
      surface tensions of structure breaking bicarbonate solutions at equivalent
      concentrations. This difference in surface tension and its variation with salt
      concentration is related to the organization of water and ions at the
      air/solution interface. Spectral results from SFVS show at equivalent
      concentrations that, for the carbonate solution, the strong water structure
      signal of 3200 cm(-1) at the air/carbonate solution interface is increased by a
      factor of 4 when compared to the same signal for the air/bicarbonate solution
      interface, which spectrum is weaker than the spectrum for the air/water interface
      in the absence of salt. These results from SFVS are explained by the results from
      MDS which show that in the case of carbonate solutions the structure making
      carbonate ions are excluded from the interfacial water region which region is
      extended in depth. On the other hand, in the case of bicarbonate solutions, the
      bicarbonate ions are accommodated in the interfacial water region and there is no
      evidence of an increase in the extent of water structure. These SFVS experimental
      and MD simulation results provide further information to understand interfacial
      phenomena of soluble salts at the molecular level.

PMID- 18035370
TI  - Kir2.x inward rectifier potassium channels are differentially regulated by
      adrenergic alpha1A receptors.
AB  - Inhibition of I(K1) currents by adrenergic alpha(1) receptors has been observed
      in cardiomyocytes and has been linked to arrhythmogenesis in an animal model.
      Both PKC-dependent and PKC-independent pathways have been implied in this
      regulation. The underlying molecular mechanisms, however, have not been
      elucidated to date. The molecular basis of native I(K1) current is mainly formed
      by Kir2.1 (KCNJ2), Kir2.2 (KCNJ12) and Kir2.3 (KCNJ4) channels that are
      differentially regulated by protein kinases. We therefore sought to investigate
      the role of those different Kir2.x channel subunits in this regulation and to
      identify the major signalling pathways involved. Adrenergic alpha(1A) receptors
      (the predominant cardiac isoform) were co-expressed with cloned Kir2.1, Kir2.2
      and Kir2.3 channels in Xenopus oocytes and electrophysiological experiments were
      performed using two-microelectrode voltage clamp. Native I(K1) currents were
      measured with the whole-cell patch clamp technique in isolated rat ventricular
      cardiomyocytes. Activation of co-expressed adrenergic alpha(1A) receptors by
      phenylephrine induced differential effects in Kir2.x channels. No effect was
      noticed in Kir2.1 channels. However, a marked inhibitory effect was observed in
      Kir2.2 channels. This regulation was not attenuated by inhibitors of PKC, CamKII
      and PKA (chelerythrine, KN-93, KT-5720), and mutated Kir2.2 channels lacking
      functional phosphorylation sites for PKC and PKA exhibited the same effect as
      Kir2.2 wild-type channels. By contrast, the regulation could be suppressed by the
      general tyrosine kinase inhibitor genistein and by the src tyrosine kinase
      inhibitor PP2 indicating an essential role of src kinases. This finding was
      validated in rat ventricular cardiomyocytes where co-application of PP2 strongly
      attenuated the inhibitory regulation of I(K1) current by adrenergic alpha(1)
      receptors. The inactive analogue PP3 was tested as negative control for PP2 and
      did not reproduce the effects of PP2. In Kir2.3 channels, a marked inhibitory
      effect of alpha(1A) receptor activation was observed. This regulation could be
      attenuated by inhibition of PKC with chelerythrine or with Ro-32-0432, but not by
      tyrosine kinase inhibition with genistein. In summary, on the molecular level the
      inhibitory regulation of I(K1) currents by adrenergic alpha(1A) receptors is
      probably based on effects on Kir2.2 and Kir2.3 channels. Kir2.2 is regulated via
      src tyrosine kinase pathways independent of protein kinase C, whereas Kir2.3 is
      inhibited by protein kinase C-dependent pathways. Src tyrosine kinase pathways
      are essential for the inhibition of native I(K1) current by adrenergic alpha(1)
      receptors. This regulation may contribute to arrhythmogenesis under adrenergic
      stimulation.

PMID- 18035371
TI  - Structure of the chloroplast signal recognition particle (SRP) receptor: domain
      arrangement modulates SRP-receptor interaction.
AB  - The signal recognition particle (SRP) pathway mediates co-translational targeting
      of nascent proteins to membranes. Chloroplast SRP is unique in that it does not
      contain the otherwise universally conserved SRP RNA, which accelerates the
      association between the SRP guanosine-5'-triphosphate (GTP) binding protein and
      its receptor FtsY in classical SRP pathways. Recently, we showed that the SRP and
      SRP receptor (SR) GTPases from chloroplast (cpSRP54 and cpFtsY, respectively) can
      interact with one another 400-fold more efficiently than their bacterial
      homologues, thus providing an explanation as to why this novel chloroplast SRP
      pathway bypasses the requirement for the SRP RNA. Here we report the crystal
      structure of cpFtsY from Arabidopsis thaliana at 2.0 A resolution. In this
      chloroplast SR, the N-terminal "N" domain is more tightly packed, and a more
      extensive interaction surface is formed between the GTPase "G" domain and the N
      domain than was previously observed in many of its bacterial homologues. As a
      result, the overall conformation of apo-cpFtsY is closer to that found in the
      bacterial SRP*FtsY complex than in free bacterial FtsY, especially with regard to
      the relative orientation of the N and G domains. In contrast, active-site
      residues in the G domain are mispositioned, explaining the low basal GTP binding
      and hydrolysis activity of free cpFtsY. This structure emphasizes proper N-G
      domain arrangement as a key factor in modulating the efficiency of SRP-receptor
      interaction and helps account, in part, for the faster kinetics at which the
      chloroplast SR interacts with its binding partner in the absence of an SRP RNA.

PMID- 18035372
TI  - The solution structure of the adhesion protein Bd37 from Babesia divergens
      reveals structural homology with eukaryotic proteins involved in membrane
      trafficking.
AB  - Babesia divergens is the Apicomplexa agent of the bovine babesiosis in Europe:
      this infection leads to growth and lactation decrease, so that economical losses
      due to this parasite are sufficient to require the development of a vaccine. The
      major surface antigen of B. divergens has been described as a 37 kDa protein
      glycosyl phosphatidyl inositol (GPI)-anchored at the surface of the merozoite.
      The immuno-prophylactic potential of Bd37 has been demonstrated, and we present
      here the high-resolution solution structure of the 27 kDa structured core of Bd37
      (Delta-Bd37) using NMR spectroscopy. A model for the whole protein has been
      obtained using additional small angle X-ray scattering (SAXS) data. The knowledge
      of the 3D structure of Bd37 allowed the precise epitope mapping of antibodies on
      its surface. Interestingly, the geometry of Delta-Bd37 reveals an intriguing
      similarity with the exocyst subunit Exo84p C-terminal region, an eukaryotic
      protein that has a direct implication in vesicle trafficking. This strongly
      suggests that Apicomplexa have developed in parallel molecular machines similar
      in structure and function to the ones used for endo- and exocytosis in eukaryotic
      cells.

PMID- 18035373
TI  - Crosstalk between the protein surface and hydrophobic core in a core-swapped
      fibronectin type III domain.
AB  - Two homologous fibronectin type III (fnIII) domains, FNfn10 (the 10th fnIII
      domain of human fibronectin) and TNfn3 (the third fnIII domain of human
      tenascin), have essentially the same backbone structure, although they share only
      approximately 24% sequence identity. While they share a similar folding mechanism
      with a common core of key residues in the folding transition state, they differ
      in many other physical properties. We use a chimeric protein, FNoTNc, to
      investigate the molecular basis for these differences. FNoTNc is a core-swapped
      protein, containing the "outside" (surface and loops) of FNfn10 and the
      hydrophobic core of TNfn3. Remarkably, FNoTNc retains the structure of the parent
      proteins despite the extent of redesign, allowing us to gain insight into which
      components of each parent protein are responsible for different aspects of its
      behaviour. Naively, one would expect properties that appear to depend principally
      on the core to be similar to TNfn3, for example, the response to mutations,
      folding kinetics and side-chain dynamics, while properties apparently determined
      by differences in the surface and loops, such as backbone dynamics, would be more
      like FNfn10. While this is broadly true, it is clear that there are also
      unexpected crosstalk effects between the core and the surface. For example, the
      anomalous response of FNfn10 to mutation is not solely a property of the core as
      we had previously suggested.

PMID- 18035374
TI  - Structures of mutants of cellulase Cel48F of Clostridium cellulolyticum in
      complex with long hemithiocellooligosaccharides give rise to a new view of the
      substrate pathway during processive action.
AB  - An efficient breakdown of lignocellulosic biomass is a prerequisite for the
      production of second-generation biofuels. Cellulases are key enzymes in this
      process. We crystallized complexes between hemithio-cello-deca and dodecaoses and
      the inactive mutants E44Q and E55Q of the endo-processive cellulase Cel48F, one
      of the most abundant cellulases in cellulosomes from Clostridium cellulolyticum,
      to elucidate its processive mechanism. In both complexes, the
      cellooligosaccharides occupy similar positions in the tunnel part of the active
      site but are more or less buried into the cleft, which hosts the active site. In
      the E44Q complex, it proceeds along the upper part of the cavity, while it
      occupies in the E55Q complex the same productive binding subsites in the lower
      part of the cavity that have previously been reported in
      Cel48F/cellooligosaccharide complexes. In both cases, the sugar moieties are
      stabilized by stacking interactions with aromatic side chains and H bonds. The
      upper pathway is gated by Tyr403, which blocks its access in the E55Q complex and
      offers a new stacking interaction in the E44Q complex. The new structural data
      give rise to the hypothesis of a two-step mechanism in which processive action
      and chain disruption occupy different subsites at the end of their trajectory. In
      the first part of the mechanism, the chain may smoothly slide up to the leaving
      group site along the upper pathway, while in the second part, the chain is
      cleaved in the already described productive binding position located in the lower
      pathway. The solved native structure of Cel48F without any bound sugar in the
      active site confirms the two side-chain orientations of the proton donor Glu55 as
      observed in the complex structures.

PMID- 18035375
TI  - The role of moral objections to suicide in the assessment of suicidal patients.
AB  - BACKGROUND: Moral and religious objections to suicide (MOS) are reported to be
      associated with less suicidal behavior in depressed patients, and are proposed to
      act as a protective factor against suicidal behavior. It is unclear whether MOS
      are a protective factor against suicide attempt per se, or if this effect is
      mediated through other variables. METHOD: Depressed inpatients (n=265) reporting
      low or high MOS were compared on history of suicidal behaviour, demographic and
      clinical characteristics. RESULTS: Patients with low MOS had significantly more
      lifetime suicide attempts, were more often without religious affiliation, had
      greater depression severity, hopelessness and trait impulsivity, less anxiety and
      fewer reasons for living. Logistic regression revealed that lower MOS was
      independently associated with suicide attempt. CONCLUSIONS: Moral and religious
      objections to suicide may serve as a protective factor against suicidal acts
      given their unique association with less suicidal behavior in depressed
      inpatients.

PMID- 18035376
TI  - Identification of an Arg35X mutation in the PDCD10 gene in a patient with
      cerebral and multiple spinal cavernous malformations.
AB  - Although cerebral cavernous malformations (CCMs) are not uncommon, the concurrent
      finding of cavernous malformations (CMs) both in the brain and spinal cord is
      quite rare. Furthermore, multiple spinal cord CMs are extremely rare with only a
      few cases being reported thus far. Recently, we encountered a 33-year-old Korean
      male with both CCM and multiple spinal intramedullary CMs. The patient complained
      of seizure and right chest paresthesia. The lesions were located throughout the
      neuraxis including the cerebral hemisphere, brain stem, and cervical and thoracic
      spinal cords. Molecular analysis of the KRIT1 (CCM1), CCM2, and PDCD10 (CCM3)
      genes identified a heterozygous nonsense mutation (c.103C>T; Arg35X) in the
      PDCD10 gene, which was reported previously in a CCM family. The patient denied a
      family history, however, his daughter had an identical mutation, but was
      asymptomatic. Three months later, after identifying the mutation in the father
      and the daughter, the daughter presented with seizure. To the best of our
      knowledge, this is the first report of an association between a mutation in the
      PDCD10 gene and spinal CMs.

PMID- 18035377
TI  - Oxygenation and establishment of thermogenesis in the avian embryo.
AB  - The production of heat (or thermogenesis) and its response to cold improve very
      quickly around birth in both mammals and birds. The mechanisms for such rapid
      perinatal development are not fully understood. Previous experiments with
      hyperoxia suggested that, during the last phases of incubation, eggshell and
      membranes might pose a limit to oxygen availability. Hence, it was hypothesized
      that an improvement in oxygenation by opening the eggshell may contribute to the
      establishment of thermogenesis. Thermogenesis and its response to cold were
      measured by indirect calorimetry, in warm (38 degrees C) conditions and during 1
      h exposure to 30 degrees C. Both improved throughout the various phases of the
      hatching process. During the latest incubation phases (internal pipping, IP, and
      star fracture of external pipping, EP), the removal of the eggshell in the region
      above the air cell raised metabolic rate both in warm and cold conditions (in IP)
      or the thermogenic response to cold (in EP). Adding hyperoxia after opening the
      eggshell caused no further increase in the thermogenic response. In cold
      incubated embryos thermogenesis during the EP phase was much less than normal; in
      these embryos, increasing the oxygen availability did not improve thermogenesis.
      We conclude that oxygenation contributes to the maturation of the thermogenic
      mechanisms in the perinatal period as long as these mechanisms have initiated
      their normal developmental process.

PMID- 18035378
TI  - First results on the study of metal contamination along the Corsican coastline
      using Posidonia oceanica.
AB  - This study aims at determining the metal concentrations in blades and sheaths of
      Posidonia oceanica adult leaves, in 16 stations of the Corsican coastline. It
      shows that except for Cr, all the metals are preferentially accumulated in the
      blades. This result is particularly interesting as it means that trace metals
      analyses may be carried out only on the blades avoiding thus the removal of the
      shoots. Moreover, this study shows that metal concentrations generally fall
      within the range of the lowest values available in literature and may reflect the
      "background noise" of the Mediterranean. Station 15 (Canari) can however be
      distinguished from the others due to its high Co, Cr and Ni concentrations. This
      result may be related to the presence of a previous asbestos mine, located near
      this station. Therefore, this study reinforces the relevance of the use of P.
      oceanica as a tracer of metal contamination.

PMID- 18035379
TI  - Influence of GSTM1 null and low repair XPC PAT+ on anti-B[a]PDE-DNA adduct in
      mononuclear white blood cells of subjects low exposed to PAHs through smoking and
      diet.
AB  - The influence of low-activity NER genotypes (XPC PAT-/+, XPA-A23G, XPD Asp312Asn,
      XPD Lys751Gln) and GSTM1 (active or null) was evaluated on anti-benzo[a]pyrene
      diol epoxide-(B[a]PDE)-DNA adduct formed in the lymphocyte plus monocyte fraction
      (LMF). The sample population consisted of 291 healthy subjects with low exposure
      to polycyclic aromatic hydrocarbons (PAHs) (B[a]P) through their smoking (n=126
      smokers) or dietary habits (n=165 non-smokers with high (>or=52 times/year)
      consumption of charcoaled meat or pizza). The bulky anti-B[a]PDE-DNA adduct
      levels were detected by HPLC/fluorescence analysis and genotypes by PCR. Anti
      B[a]PDE-DNA was present (>or=0.5 adducts/10(8) nucleotides) in 163 (56%) subjects
      (median (range) 0.77 (0.125-32.0) adducts/10(8) nucleotides), with smokers
      showing a significantly higher adduct level than non-smokers with high
      consumption of PAH-rich meals (P<0.01). Our exposed-sample population with
      unfavourable XPC PAT+/- or +/+ and GSTM1 null genotypes has the significantly
      highest adduct level (P<0.01). Taking into account tobacco smoke and diet as
      sources of exposure to B[a]P, low-activity XPC PAT+ shows a major role in smokers
      (P<0.05) and GSTM1 null in non-smokers with frequent consumption of PAH-rich
      meals (P<0.01). The modulation of anti-B[a]PDE-DNA adduct in the LMF by GSTM1
      null and low-activity XPC PAT+ polymorphisms may be considered as potential
      genetic susceptibility factors that can modify individual responses to low PAH
      (B[a]P) genotoxic exposure, with the consequent risk of cancer in the general
      population.

PMID- 18035380
TI  - Association of genetic polymorphisms in glutathione S-transferases and
      susceptibility to head and neck cancer.
AB  - Polymorphism in glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1)
      and interaction with environmental factors such as tobacco (smoking or chewing)
      and alcohol on susceptibility to head and neck squamous cell carcinoma (HNSCC)
      was studied in a case-control study. The study group consisted of 175 patients
      suffering from HNSCC and 200 age matched healthy controls. Statistical analysis
      showed an increase in risk to HNSCC in the patients with null genotype of GSTM1
      (OR: 2.02; 95% CI: 1.32-3.10; P=0.001) or GSTT1 (OR: 1.66; 95% CI: 1.02-2.69;
      P=0.04), though the risk was not found to be significant when adjusted for age,
      sex, smoking, tobacco chewing or alcohol use by multivariate logistic regression
      model. Our data further showed that combination of deletion genotypes of GST
      (GSTM1 and GSTT1) confer an even higher risk of HNSCC. Interestingly, GSTP1 wild
      type genotype in combination with GSTM1 null or GSTT1 null genotype increased
      susceptibility for HNSCC (OR: 2.49 and 2.75, respectively). Likewise a much
      greater risk for HNSCC was observed in the patients carrying a genotype
      combination of GSTM1 null, GSTT1 null and GSTP1 (Ile/Ile) (OR: 4.47; 95% CI: 1.62
      12.31; P=0.002). Our data have further provided evidence that tobacco chewing and
      alcohol consumption are the important risk factors for HNSCC. The interaction
      between tobacco chewing and null genotype of GSTM1 or GSTT1 resulted in about 3.5
      and 2.2-fold increase in the risk respectively in the patients when compared to
      those not chewing tobacco. Alcohol use resulted in more than 4-fold increase in
      the risk in the patients with null genotype of GSTM1 as compared to those who are
      non-drinkers. Alcohol consumption also increased the risk (approx. 3-fold) in the
      cases with null genotype of GSTT1, though the association was not found to be
      significant when compared to non-drinkers. Our data have provided evidence that
      GST polymorphism modifies the susceptibility to HNSCC and have further
      demonstrated importance of gene-environment interaction in modulating the risk to
      HNSCC.

PMID- 18035381
TI  - Quasi-movements: a novel motor-cognitive phenomenon.
AB  - We introduce quasi-movements and define them as volitional movements which are
      minimized by the subject to such an extent that finally they become undetectable
      by objective measures. They are intended as overt movements, but the absence of
      the measurable motor responses and the subjective experience make quasi-movements
      similar to motor imagery. We used the amplitude dynamics of
      electroencephalographic alpha oscillations as a marker of the regional
      involvement of cortical areas in three experimental tasks: movement execution,
      kinesthetic motor imagery, and quasi-movements. All three conditions were
      associated with a significant suppression of alpha oscillations over the
      sensorimotor hand area of the contralateral hemisphere. This suppression was
      strongest for executed movements, and stronger for quasi-movements than for motor
      imagery. The topography of alpha suppression was similar in all three conditions.
      Proprioceptive sensations related to quasi-movements contribute to the assumption
      that the "sense of movement" can originate from central efferent processes. Quasi
      movements are also congruent with the postulated continuity between motor imagery
      and movement preparation/execution. We also show that in healthy subjects quasi
      movements can be effectively used in brain-computer interface research leading to
      a significantly smaller classification error ( approximately 47% of relative
      decrease) in comparison to the errors obtained with conventionally used motor
      imagery strategies.

PMID- 18035383
TI  - Systematic review on the prevalence of diabetes, overweight/obesity and physical
      inactivity in Ghanaians and Nigerians.
AB  - OBJECTIVE: To review the prevalence of diabetes, obesity and physical inactivity
      among Ghanaians and Nigerians in Africa, Europe and North America. METHODS: This
      systematic literature review used MEDLINE 1966--2005, EMBASE 1980--2005 and cited
      references to identify relevant studies on Ghanaians and Nigerians. RESULTS: No
      studies on Ghanaians or Nigerians in Europe or North America have been reported.
      Sixteen studies in Africa were included; 13 on Nigerians and three on Ghanaians.
      The data were limited, poorly reported and not easily comparable. Pooled analysis
      was not possible. Precise time trend analysis was not possible, but diabetes
      seemed rare at 0.2% in urban Ghana in 1963 and 1.65% in urban Nigeria in 1985.
      The prevalence of diabetes in Nigerian adults (age > or = 40 years) in 2000 was
      6.8% [confidence intervals (CI) 4.6-9.0]. In Ghana, the prevalence of diabetes in
      adults (age > or = 25 years) was 6.3% (CI 5.6-7.0) in 1998. Obesity (body mass
      index > or = 30) among Nigerian adults was 8.8% (CI 7.0-10.6) in 2000, and
      obesity in Ghanaian adults (> or = 25 years) was 14.1% (CI 13.1-15.1%) in 1998.
      Various studies reported that 25-57% of Nigerians were physically inactive.
      CONCLUSION: Although weak, the evidence base points to a rise in diabetes
      prevalence in Ghana and Nigeria, with major urban-rural differences. There is an
      urgent need for accurate and comparable surveys on diabetes and its risk factors
      among Nigerians and Ghanaians. Effective public health policies are vital to
      control the diabetes epidemic.

PMID- 18035382
TI  - Effects of chronic adult dietary restriction on spatial learning in the aged F344
      x BN hybrid F1 rat.
AB  - Dietary restriction (DR) has been shown to increase life span and reduce disease
      incidence across a variety of species. Recent research suggests that chronic
      adult DR may also alter age-related cognitive decline. The purpose of this study
      was twofold: (1) to examine the potential deficits in spatial learning ability in
      the aged F344 x BN hybrid F1 rat with specific attention to the contributory
      effects of motoric impairments and (2) to determine the influence of chronic
      adult DR on any such impairments. The Morris water maze (MWM) task was employed
      with a 1.8 m diameter tank, 10 cm2 escape platform, 28 degrees C water, and an
      automated collapsing central starting platform. Spatial learning impairments in
      the aged rats were evident on all dependent measures during training and the
      probe test. Motoric function, as reflected in measures of strength and locomotion
      demonstrated profound age-related performance impairments that were attenuated by
      chronic adult DR. The present data also replicate previous reports, indicating
      that DR attenuates the age-related impairments of performance in the MWM as
      indexed by the latency measure in acquisition, but critically was dissociated
      from any DR effect on measures of preference and, more critically, accuracy in
      the probe test. Collectively, the most parsimonious interpretation of DR effects
      on MWM performance would appear to be the preservation of motoric, and not
      cognitive, function.

PMID- 18035384
TI  - [Mandibular osteoradionecrosis: part I: severity factors].
AB  - INTRODUCTION: The severe evolution for some patient presenting with
      osteoradionecrosis, even if classified in the same stages as other patients,
      suggests that there are aggravating factors. MATERIAL AND METHOD: A retrospective
      study was made between 1992 and 2002 on all patient operated for mandibular
      osteoradionecrosis. Fifty-nine patients were included and the mandibular defects
      were reconstructed with a bone or a composite free flap (fibula 21%, iliac crest
      49%, scapula 6%, antebrachial 3%), and with a periosteal free flap (13%).
      RESULTS: The study included severe cases (87% of stage II or III) operated on
      several times without success. Free flap reconstruction was successful in 90% of
      the cases. However, complications were present in 60% of cases (24% minor
      complications, 48% major complications), and were more frequent with a higher
      stage. The analysis allowed identifying morbidity factors. DISCUSSION: Studying
      the morbidity allowed identifying severity factors of osteoradionecrosis;
      spontaneous onset, important irradiation (important dose, bone proximity of the
      tumor, bilateral damage), vascular damage (symphyseal localization, lack of
      sequestrum, facial artery ligature, active tobacco addiction), actinomycosis
      colonization, non-observance of medical treatment. Understanding aggravating
      factors should allow us to offer more efficient surgery on an early
      osteoradionecrosis stage, also decreasing the morbidity linked to reconstructive
      surgery.

PMID- 18035385
TI  - Potential antimalarial activity of indole alkaloids.
AB  - New antimalarial treatments are now urgently required, following the emergence of
      resistance to the most used drugs. Natural products contribute greatly to the
      therapeutic arsenal in this area, including artemisinin and quinine (and
      atovaquone, semi-synthetic). Among the natural products, indole alkaloids
      represent an interesting class of compounds. Screening carried out to date has
      revealed several substances active in vitro under the micromolar range and with a
      good selectivity index. This review covers the indole alkaloids with high
      antiplasmodial activity (in vitro and in vivo) isolated from natural sources, and
      is organized according to the different chemical structures of the alkaloids.

PMID- 18035386
TI  - Preferential organ distribution of methylselenol source Se-methylselenocysteine
      relative to methylseleninic acid.
AB  - It has been proposed that Se-methylselenocysteine (MeSeCys) and methylseleninic
      acid (MSA(IV)) are efficiently transformed through the beta-lyase and reduction
      reactions, respectively, into methylselenol, the assumed biologically active
      selenometabolite responsive for the anti-carcinogenicity and anti-oxidant actions
      of selenium. The bioavailability and distribution of the two selenium sources in
      major organs/tissues were compared under exactly identical conditions. Namely,
      labeled selenium sources (76)Se-MeSeCys and (77)Se-MSA(IV), at a single oral dose
      of 10 microg Se/kg body weight each, were administered simultaneously to rats
      that had been depleted of natural abundance selenium with a single isotope
      (78)Se. The same dose of (82)Se-selenite was also administered as a reference
      selenium source. The distributions of the three labeled selenium isotopes were
      determined 3 h after the administration in 13 organs/tissues/blood. MeSeCys was
      taken up more efficiently by most organs, especially the pancreas and duodenum,
      than MSA(IV) and selenite, the latter two sources being taken up similarly to
      each other except for in the kidney, liver, and spleen, where the three labeled
      isotopes were detected at comparable concentrations. The labeled selenium in the
      liver supernatant was speciated by HPLC inductively coupled argon plasma-mass
      spectrometry (ICP-MS), and it was suggested that MeSeCys was delivered in its
      intact form to organs, and then transformed into methylselenol. In addition to
      the known properties of that MeSeCys is chemically more stable than MSA(IV) and
      is a naturally occurring edible product, and that MeSeCys produces methylselenol
      much more efficiently than a homologous selenoamino acid selenomethionine, the
      present study revealed that MeSeCys is more efficiently distributed than MSA(IV)
      in its intact form, and then produces methylselenol, suggesting that MeSeCys is
      the best methylselenol source in most organs/tissues.

PMID- 18035387
TI  - Tropism and toxicity of adeno-associated viral vector serotypes 1, 2, 5, 6, 7, 8,
      and 9 in rat neurons and glia in vitro.
AB  - Recombinant adeno-associated viral (rAAV) vectors are frequently used for gene
      delivery to the central nervous system and are capable of transducing neurons and
      glia in vitro. In this study, seven serotypes of a rAAV vector expressing green
      fluorescent protein (GFP) were characterized for tropism and toxicity in primary
      cortical cells derived from embryonic rat brain. At 2 days after transduction,
      serotypes 1 and 5 through 8 expressed GFP predominately in glia, but by 6 days
      post-transduction expression was neuronal except for AAV5. AAV2 and 9 produced
      minimal GFP expression. Using cell viability assays, toxicity was observed at
      higher multiplicities of infection (MOI) for all serotypes except AAV2 and 9. The
      toxicity of AAV1 and 5-8 affected mostly glia as indicated by a loss of glial
      marker immunoreactivity. A frameshift mutation in the GFP gene reduced overall
      toxicity for serotypes 1, 5 and 6, but not 7 and 8 suggesting that the toxicity
      was not solely due to the overexpression of GFP. Collectively, a differential
      tropism and toxicity was observed among the AAV serotypes on primary cortical
      cultures with an overall preferential glial transduction and toxicity.

PMID- 18035388
TI  - Contribution of the leader sequence to homologous viral interference among Sendai
      virus strains.
AB  - Sendai viruses (SeV) derived from persistent infection have a capacity to
      interfere with co-infected wild-type virus. Here we showed that interference was
      also caused by the laboratory strains Z and Nagoya. The leader mutations A(20)U
      and A(24)U related to viral adaptation from mice to chicken eggs significantly
      affected the capacity for viral interference, especially through genome
      amplification. Furthermore, recombinant SeV that possessed the mutations A(34)G
      and G(47)A, which are commonly found in the leader sequence of persistent
      infection-derived SeV strains, had an increased capacity for interference. Viral
      replication of human parainfluenza viruses 1, 2, and 3, but not the mumps virus
      or Newcastle disease virus, was suppressed by co-infection of a persistent
      infection-derived SeV strain, suggesting suppression of closely related human
      paramyxoviruses. These results indicate that homologous interference is partly
      dependent on the promoter sequence and further suggest involvement of promoter
      activity for genome amplification related to host factors in viral interference.

PMID- 18035389
TI  - Selective removal of copper and lead ions by diethylenetriamine-functionalized
      adsorbent: behaviors and mechanisms.
AB  - The selective removal of copper and lead ions from aqueous solutions by
      diethylenetriamine (DETA)-functionalized polymeric adsorbent was investigated.
      The adsorbent was prepared by amination of the micro-beads synthesized from
      glycidyl methacrylate and trimethylolpropane trimethacrylate co-polymerization
      (denoted as P-DETA). In the single metal species system (only copper or lead ions
      present), P-DETA was found to adsorb copper ions or lead ions significantly (with
      a slightly higher adsorption uptake capacity for lead ions than copper ions).
      However, P-DETA displayed an excellent selectivity in the adsorption of copper
      ions over lead ions in the binary metal species system (with both copper and lead
      ions present). It was also found that initially (or previously) adsorbed lead
      ions on P-DETA were displaced, even completely, by subsequently adsorbed copper
      ions from the solution but the case was not vice versa. The greater
      electronegativity of copper ions than lead ions was identified as the major
      factor that caused P-DETA to selectively adsorb copper ions over lead ions during
      competitive adsorption in the binary metal species system. It was speculated that
      the displacement of already adsorbed lead ions on P-DETA by subsequently adsorbed
      copper ions was through an adjacent attachment and repulsion mechanism. P-DETA
      has been shown to have the potential to be used as an effective adsorbent for the
      removal as well as selective recovery of heavy metal ions in water or wastewater
      treatment.

PMID- 18035390
TI  - Rhamnolipid biosurfactant mixtures for environmental remediation.
AB  - This study investigated the efficiency of rhamnolipid biosurfactant and synthetic
      surfactant mixtures for improving the interfacial activity of the surfactant
      system against several light non-aqueous-phase liquids (LNAPLs). Since the
      rhamnolipid biosurfactant proved to be relatively hydrophilic, we hypothesized
      that mixtures of rhamnolipid biosurfactants with more hydrophobic synthetic
      surfactants would produce lower interfacial tensions (IFTs) than an individual
      rhamnolipid biosurfactant. The minimum IFT observed for rhamnolipid alone and
      toluene (0.03mN/m) was one order of magnitude lower than for hexane, decane, and
      hexadecane, demonstrating the relatively hydrophilic nature of the rhamnolipid.
      The low IFTs even at the low surfactant concentration used suggest mobilization
      as the dominant oil-removal mechanism versus supersolubilization. The critical
      micelle concentration (CMC) and critical microemulsion concentration (CmicroC) of
      the rhamnolipid were found to be 0.001w/w% (0.019mM) and 0.01w/w% (0.19mM),
      respectively. Three alkyl propoxylated (PO) sulfate synthetic surfactants were
      individually mixed with the rhamnolipid. As the hydrophobicity of the surfactant
      mixture approached that of the hydrocarbon, IFT values decreased by one to two
      orders of magnitude below that achieved with individual surfactants. This work
      shows that the rhamnolipid has excellent phase behavior at low concentrations and
      can be used in surfactant mixtures to achieve the low IFT values needed for
      environmental remediation, enhanced oil recovery (EOR), and other applications.

PMID- 18035391
TI  - Evaluation of energy-conversion efficiencies in microbial fuel cells (MFCs)
      utilizing fermentable and non-fermentable substrates.
AB  - We established the first complete electron-equivalent balances in microbial fuel
      cells (MFCs) fed with non-fermentable (acetate) and fermentable (glucose)
      electron donors by experimentally quantifying current, biomass, residual organic
      compounds, H(2), and CH(4) gas. The comparison of the two donors allowed us to
      objectively evaluate the diversion of electron flow to non-electricity sinks for
      fermentable donors, leading to different behaviors in energy-conversion
      efficiency (ECE) and potential efficiency (PE). Electrical current was the most
      significant electron sink in both MFCs, being 71% and 49%, respectively, of the
      initial COD applied. Biomass and residual organic compounds, the second and third
      greatest sinks, respectively, were greater in the glucose-fed MFC than in the
      acetate-fed MFC. We detected methane gas only in the glucose-fed MFC, and this
      means that anode-respiring bacteria (ARB) could out-compete acetoclastic
      methanogens. The ECE was 42% with acetate, but was only 3% with glucose. The very
      low ECE for glucose was mostly due to a large increase of the anode potential,
      giving a PE of only 6%. Although the glucose-fed MFC had the higher biomass
      density on its anode, it had a very low current density, which supports the fact
      that the density of ARB was very low. This led to slow kinetics for electron
      transfer to the anode and accentuated loss due to the substrate-concentration
      gradient in the anode-biofilm. The large drop of PE with low current, probably
      caused by a low ARB density and electron (e(-)) donor concentration, resulted in
      a poor maximum power density (9.8mW/m(2)) with glucose. In contrast, PE reached
      59% along with high current for acetate and the maximum power density was
      360mW/m(2).

PMID- 18035392
TI  - Quantitative assessment of soil parameter (KD and TC) estimation using DGT
      measurements and the 2D DIFS model.
AB  - Diffusive gradients in thin films (DGT) is a dynamic, in situ measuring technique
      that can be used to supply diverse information on concentrations and behaviour of
      solutes. When deployed in soils and sediments, quantitative interpretation of DGT
      measurements requires the use of a numerical model. An improved version of the
      DGT induced fluxes in soils and sediments model (DIFS), working in two dimensions
      (2D DIFS), was used to investigate the accuracy with which DGT measurements can
      be used to estimate the distribution coefficient for labile metal (KD) and the
      response time of the soil to depletion (TC). The 2D DIFS model was used to obtain
      values of KD and TC for Cd, Zn and Ni in three different soils, which were
      compared to values determined previously using 1D DIFS for these cases. While the
      1D model was shown to provide reasonable estimates of KD, the 2D model refined
      the estimates of the kinetic parameters. Desorption rate constants were shown to
      be similar for all three metals and lower than previously thought. Calculation of
      an error function as KD and TC are systematically varied showed the spread of KD
      and TC values that fit the experimental data equally well. These automatically
      generated error maps reflected the quality of the data and provided an appraisal
      of the accuracy of parameter estimation. They showed that in some cases parameter
      accuracy could be improved by fitting the model to a sub-set of data.

PMID- 18035393
TI  - Mobility of adsorbed arsenic in two calcareous soils as influenced by water
      extract of compost.
AB  - The mobility of arsenic (As) in soil affects both the bio-toxicity of As and the
      groundwater quality, which in turn indirectly affects the quality of edible part
      of crops and human health, if the crops were irrigated with As contaminated
      groundwater. A vertical soil column simulates the depth of a soil profile in a
      real soil environment. Thus soil column experiment is much more pertinent to soil
      environment than a batch experiment to simulate solute movement as well as
      leaching through soil profile. A laboratory soil column experiment was conducted
      to determine the extent of As leaching from soil percolated with influent that
      contained organic substances. The water extract of compost (WEC) was used as the
      source of organic substances. The results of As breakthrough curves (BTCs) showed
      that less pore volumes of influents were required to reach the relative
      concentration ratio of 1 (C/C0=1) for the two calcareous soils treated with
      influent that contained WEC. The concentrations of As in the column effluents of
      soils percolated with 0.01M KCl in WEC were significantly higher than those
      percolated with 0.01M KCl with the same volumes of effluents collected. This
      clearly indicates that dissolved as well as deprotonated organic substances which
      are negatively charged have higher potential for competing the adsorption sites
      with As on soils, leading to increasing mobility of As in soil and associated
      environments. Further, it is observed that the characteristics of soil components
      related to As adsorption affected the adsorption as well as desorption processes
      and subsequent mobility of As in soil environment as influenced by organic
      substances.

PMID- 18035394
TI  - Evaluation of reproductive safety of beta-sitosterol on the American mink
      (Neovison vison).
AB  - beta-Sitosterol is a weakly estrogenic phytosterol used extensively in functional
      foods to lower elevated serum cholesterol concentrations due to its inhibitory
      action on intestinal cholesterol absorption. It caused previously decreased sex
      steroid concentrations in fish and lowered sperm counts in rats. In the American
      mink (Neovison vison), litter size increased slightly due to dietary beta
      sitosterol supplement. The aim of the present experiment was to conduct a dose
      response study on the effects of beta-sitosterol on the reproduction of the
      American mink. Juvenile male and female mink (n=480) were exposed to 0, 5, 10 or
      50 mg of peroral beta-sitosterol kg(-1)d(-1) for 10 months. After 3 months of
      exposure in November, 15 males per group were sacrificed and general biochemical
      variables reflecting overall health were determined. The beta-sitosterol-treated
      male mink had increased absolute and relative masses of intraabdominal fat and
      higher blood hemoglobin and serum high-density lipoprotein cholesterol
      concentrations. In spring, the top-rated male mink were mated with multiple
      females within each study group and reproductive success was assessed. No
      differences in the reproductive performance of the males (10-11 per group) or
      females (47-50 per group) could be detected in the exposed groups and the kits of
      all groups developed in a similar manner. The results suggest that dietary beta
      sitosterol presents no significant risk to mammalian fertility.

PMID- 18035395
TI  - Concentrations and specific loads of brominated flame retardants in sewage
      sludge.
AB  - Many substances related to human activities end up in wastewater and accumulate
      in sewage sludge. The present study focuses on two classes of brominated flame
      retardants: polybrominated diphenyl ethers (BDE28, BDE47, BDE49, BDE66, BDE85,
      BDE99, BDE100, BDE119, BDE138, BDE153, BDE154, BDE183, BDE209) and
      hexabromocyclododecane (HBCD) detected in sewage sludge collected from a
      monitoring network in Switzerland. Mean concentrations (n=16 wastewater treatment
      plants) were 310, 149, 95 and 17microg per kg dry matter for decaBDE, HBCD, penta
      and octaBDE, respectively. These numbers correspond well with other studies from
      European countries. DecaBDE, HBCD, penta- and octaBDE showed average specific
      loads (load per connected inhabitant per year) in sludge of 6.1, 3.3, 2.0 and
      0.3mgcap(-1)yr(-1), respectively. This is in line with consumption and storage of
      the compounds in the environment and the anthroposphere. Discrepancies observed
      for octaBDE and HBCD can be explained by the release from materials where these
      compounds are incorporated in and/or their degradation during anaerobic sludge
      treatment. Loads from different types of monitoring sites showed that brominated
      flame retardants ending up in sewage sludge originate mainly from surface runoff,
      industrial and domestic wastewater.

PMID- 18035396
TI  - Auditory ossicles from southwest Asian Mousterian sites.
AB  - The present study describes and analyzes new Neandertal and early modern human
      auditory ossicles from the sites of Qafzeh and Amud in southwest Asia. Some
      methodological issues in the measurement of these bones are considered, and a set
      of standardized measurement protocols is proposed. Evidence of erosive
      pathological processes, most likely attributed to otitis media, is present on the
      ossicles of Qafzeh 12 and Amud 7 but none can be detected in the other Qafzeh
      specimens. Qafzeh 12 and 15 extend the known range of variation in the fossil H.
      sapiens sample in some metric variables, but morphologically, the new specimens
      do not differ in any meaningful way from living humans. In most metric
      dimensions, the Amud 7 incus falls within our modern human range of variation,
      but the more closed angle between the short and long processes stands out.
      Morphologically, all the Neandertal incudi described to date show a very straight
      long process. Several tentative hypotheses can be suggested regarding the
      evolution of the ear ossicles in the genus Homo. First, the degree of metric and
      morphological variation seems greater among the fossil H. sapiens sample than in
      Neandertals. Second, there is a real difference in the size of the malleus
      between Neandertals and fossil H. sapiens, with Neandertals showing larger values
      in most dimensions. Third, the wider malleus head implies a larger articular
      facet in the Neandertals, and this also appears to be reflected in the larger
      (taller) incus articular facet. Fourth, there is limited evidence for a potential
      temporal trend toward reduction of the long process within the Neandertal
      lineage. Fifth, a combination of features in the malleus, incus, and stapes may
      indicate a slightly different relative positioning of either the tip of the incus
      long process or stapes footplate within the tympanic cavity in the Neandertal
      lineage.

PMID- 18035397
TI  - Patterns of clavicular bilateral asymmetry in relation to the humerus: variation
      among humans.
AB  - Studies of directional asymmetry in the human upper limb have extensively
      examined bones of the arm, forearm, and hand, but have rarely considered the
      clavicle. Physiologically, the clavicle is an integrated element of the upper
      limb, transmitting loads to the axial skeleton and supporting the distal bones.
      However, clavicles develop in a manner that is unique among the bones of the
      upper limb. Previous studies have indicated that the clavicle has a right-biased
      asymmetry in diaphyseal breadth, as in humeri, radii, ulnae, and metacarpals, but
      unlike these other elements, a left-biased length asymmetry. Few studies have
      assessed how clavicular asymmetry relates to these other bones of the upper limb.
      Bilateral directional asymmetry of the clavicle is examined in relation to the
      humerus in a large, geographically diverse human sample, comparing lengths and
      diaphyseal breadths. Dimensions were converted into percentage directional (%DA)
      and absolute (%AA) asymmetries. Results indicate that humans have same-side %DA
      bias in the clavicles and humeri, and contralateral length %DA between these
      elements. Diaphyseal breadths in both clavicles and humeri are more asymmetric
      both in direction and amount-than lengths. Differences in diaphyseal asymmetry
      are shown to relate to variation in physical activities among groups, but a
      relationship between activity and length asymmetry is not supported. This further
      supports previous research, which suggests different degrees of sensitivity to
      loading between diaphyseal breadths and maximum lengths of long bones.
      Differences in lateralized behavior and the potential effects of different bone
      development are examined as possible influences on the patterns observed among
      human groups.

PMID- 18035398
TI  - Hammer or crescent wrench? Stone-tool form and function in the Aurignacian of
      southwest Germany.
AB  - The early Upper Paleolithic of Europe is associated with the appearance of
      blade/bladelet technology (e.g., Aurignacian). These industries include a wider
      range of formal tool types than seen in the Middle Paleolithic. Greater diversity
      in tool types is often interpreted as specialized tools created for specific
      tasks. This, in turn, is said to reflect dramatic behavioral shifts between
      Neandertals and modern humans. In order to test previous interpretations, it is
      necessary to have a detailed understanding of early Upper Paleolithic stone-tool
      function. Toward this end, analyses of microscopic residue and use-wear were
      undertaken on 109 stone tools from three Aurignacian sites in southwest Germany
      (Hohle Fels, Geissenklosterle, and Vogelherd). These cave sites evidenced
      remarkable residue preservation, with approximately 82% of the sample showing
      some form of functional evidence. Residues observed included hair, feathers,
      bone/antler, wood, plant tissue, phytoliths, starch grains, and resin. The
      results suggest that tool typology is not strongly linked to the processing of
      specific materials. For example, endscrapers from the sample show evidence of
      processing wood, charred wood, plants, starchy plants, birds, bone/antler, and
      animals (hair). Hairs are found on tools typologically classified as blades,
      flakes, borers, pointed blades, and combination tools (nosed endscraper-borer,
      burin-laterally-retouched blade). In the early Upper Paleolithic of southwest
      Germany, a wide range of tool types appears to have been used to process a
      diverse array of materials. These results suggest that the interpretation of
      behavioral patterns from stone tools must consider more than tool typology.

PMID- 18035399
TI  - Rapid neonatal weight gain in rats results in a renal ubiquinone (CoQ) deficiency
      associated with premature death.
AB  - We have recently reported that maternal dietary imbalance during pregnancy and
      lactation can reduce the lifespan of offspring. Rats that were growth restricted
      in utero by maternal protein restriction and underwent rapid weight gain when
      suckled by control fed dams died earlier than animals whose mothers were fed a
      control diet throughout pregnancy and lactation. We demonstrate here that
      mitochondrial abnormalities and DNA damage occur in the kidney of offspring who
      die prematurely. We have established by direct measurement and by in vitro
      supplementation that mitochondrial abnormalities occur because of a functional
      deficit of the mitochondrial cofactor coenzyme Q9 (CoQ9). These data provide
      molecular insight into the association between maternal nutrition and
      determination of offspring lifespan, and identify, a potential dietary
      intervention to prevent detrimental consequences of imbalanced maternal
      nutrition.

PMID- 18035400
TI  - Distribution of trace elements in organs of six species of cetaceans from the
      Ligurian Sea (Mediterranean), and the relationship with stable carbon and
      nitrogen ratios.
AB  - Mercury (total and organic), cadmium, lead, copper, iron, manganese, selenium and
      zinc concentrations were measured in different organs of 6 different cetacean
      species stranded in an area of extraordinary ecological interest (Cetaceans'
      Sanctuary of the Mediterranean Sea) along the coast of the Ligurian Sea (North
      West Mediterranean). Stable-isotopes ratios of carbon ((13)C/(12)C) and nitrogen
      ((15)N/(14)N) were also measured in the muscle. A significant relationship exists
      between (15)N/(14)N, mercury concentration and the trophic level. The
      distribution of essential and non-essential trace elements was studied on several
      organs, and a significant relationship between selenium and mercury, with a molar
      ratio close to 1, was found in the cetaceans' kidney, liver and spleen,
      regardless of their species. High selenium concentrations are generally
      associated with a low organic to total mercury ratio. While narrow ranges of
      concentrations were observed for essential elements in most organs, mercury and
      selenium concentrations are characterised by a wide range of variation. Bio
      accumulation and bio-amplification processes in cetaceans can be better
      understood by comparing trace element concentrations with the stable-isotopes
      data.

PMID- 18035401
TI  - Immunohistochemical analysis of hepatic ganglioside distribution following a
      partial hepatectomy and exposure to different hyperbaric oxygen treatments.
AB  - Ganglioside GM3(Neu5Ac) expression is highly increased in liver 54h following 15%
      partial hepatectomy in pre-operatively oxygenated rats. GM3(Neu5Gc), GM2, GalNAc
      GM1b and gangliosides of the neolacto-series are less affected. GM3(Neu5Ac) is a
      potent inhibitor of epidermal growth factor signaling. Since GM3(Neu5Ac) growth
      inhibitory effect depends on its cellular localization, the aim of this study was
      to detect ganglioside cellular localization during liver regeneration. The
      experiment was performed using the same rat model which previously showed
      increased ganglioside expression and more efficient liver regeneration. Frozen
      sections of liver were analyzed using confocal microscopy after labeling for
      binding of five ganglioside-specific antibodies, with or without hepatocyte
      membrane permeabilization. Ganglioside precursors, ceramide (Cer),
      monohexaosylceramide and lactosylceramide (LacCer) were determined by high
      performance thin-layer chromatography. Apoptosis was assessed by fluorescein-dUTP
      end-labeling of fragmented DNA. Liver of pre-operative oxygenated rats showed
      high perinuclear labeling of GM3(Neu5Ac) which was absent in post-operative
      oxygenated and control animals. In the same group, Cer content was lower,
      monohexaosylceramide and LacCer were absent, and content of apoptotic cells was
      significantly the lowest, compared to other groups examined (F=20.36, p=0.0001).
      These findings indicate that ganglioside GM3(Neu5Ac) may be involved in mediation
      of beneficial effects of pre-operatively oxygenation during the liver
      regeneration.

PMID- 18035402
TI  - The development of avian enteric nervous system: distribution of artemin
      immunoreactivity.
AB  - Among the factors that control neural crest cell precursors within the enteric
      nervous system, the ligands of the glial cell line-derived neurotrophic factor
      family (GFL) seem to be the most influential. Artemin, a member of the GFLs, was
      previously described only in the oesophagus and stomach of mouse embryos. In this
      study, the presence and distribution of artemin is reported in duck embryos and
      adults. Artemin immunoreactivity was apparent in the intestinal tract at
      embryonic day 7 (d7), firstly in the myenteric plexus and then in the submucous
      plexus. Later, artemin immunoreactive nerve fibres were also seen in the
      longitudinal muscle plexus, the circular muscle plexus, the plexus of the
      muscularis mucosa and in the mucosal plexus. Furthermore, at d7, weak labeling of
      artemin was detected in neurons and glial cells in the oesophagus, gastric region
      and duodenum. Subsequently, artemin was also detected in all other intestinal
      segments. Moreover, during development of the gut in the domestic duck, artemin
      immunoreactivity decreased in neuronal cell bodies, whilst it increased in
      neuronal fibres and glial cells. These findings suggest an involvement of artemin
      in the development and biology of the gut of the domestic duck.

PMID- 18035403
TI  - Antiproliferative effects of the major tea polyphenol, (-)-epigallocatechin
      gallate and retinoic acid in cervical adenocarcinoma.
AB  - OBJECTIVE: To investigate the combined effect of the major tea polyphenol, (-)
      epigallocatechin gallate (EGCG) and retinoic acid (RA) on cervical
      adenocarcinoma. METHODS: Cell growth rate was examined after treatment for 4, 7
      and 10 days with 0-100 microM EGCG and/or 1 microM RA in two cervical
      adenocarcinoma cell lines, HeLa and TMCC-1. The effect of EGCG treatment was
      examined for the induction of apoptosis by DNA ladder assay and caspase-3-related
      protease activity in cell lysate. Telomerase activity was detected by stretch PCR
      telomere extension assay. hTERT expression levels were quantified by a real-time
      PCR system. RESULTS: Combining EGCG and RA increased the antiproliferative effect
      in adenocarcinoma cell lines, whereas EGCG or RA treatment alone caused a less
      sensitive response in these cells. Neither EGCG nor RA treatment alone affected
      apoptosis and telomerase activity. The combination treatment of EGCG and RA
      induced apoptosis and inhibited telomerase activity in adenocarcinoma cell lines.
      These results were consistent with those of an antiproliferative effect of EGCG
      and/or RA in cervical adenocarcinoma cells. CONCLUSION: Our data suggest that
      EGCG and RA combined to prevent the carcinogenesis of cervical adenocarcinoma,
      induce apoptosis and inhibit telomerase activity. The treatments of combining
      EGCG and RA may be effective in preventing or treating cervical adenocarcinoma.

PMID- 18035404
TI  - E-cadherin gene polymorphisms and haplotype associated with the occurrence of
      epithelial ovarian cancer in Chinese.
AB  - BACKGROUNDS AND AIMS: E-cadherin plays an important role in the origin of
      epithelial ovarian cancer. However, the exact molecular mechanism by which this
      occurs is unknown. The polymorphisms located at the E-cadherin may contribute to
      an increased risk for certain cancers. In this paper, we studied the association
      between polymorphisms of E-cadherin and the risk of epithelial ovarian cancer.
      METHODS: We assessed the -160C/A, -347G/GA polymorphism within the promoter
      region and 3'-UTR +54C/T polymorphism of E-cadherin in epithelial ovarian cancer
      and control women. We also tested the expression of E-cadherin protein in ovarian
      cancer tissue among three genotype (3'-UTR +54C/T polymorphism) carriers.
      RESULTS: There was no significant difference in genotype distribution of the 
      160C/A and -347G/GA SNPs in the E-cadherin gene promoter region between ovarian
      cancer patients and controls, but haplotype -160A/-347GA relative to haplotype 
      160C/-347G was 48.6 (95% CI=2.9-806.2) for epithelial ovarian cancer risk. The
      C/C genotype of the 3'-UTR +54C/T polymorphism relative to the C/T+T/T genotype
      was 1.85 (95% CI=1.27-2.69) for epithelial ovarian cancer risk. E-cadherin
      protein expression in was lower in C/C genotype carriers than T allele carriers
      in ovarian cancer tissue (P=0.02). CONCLUSIONS: The C/C genotype of 3'-UTR C/T
      SNP and -160C/-374GA haplotype in E-cadherin gene may be a potential
      susceptibility factor for risk of epithelial ovarian cancer in Chinese, which
      indicated that the lower expression of E-cadherin might play an important role in
      the pathogenesis of epithelial ovarian cancer.

PMID- 18035405
TI  - Robotic radical hysterectomy with pelvic lymphadenectomy for cervical carcinoma:
      a pilot study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the feasibility and
      surgical outcome of robotic radical hysterectomy with pelvic lymphadenectomy for
      stage I cervical carcinoma using the da Vinci surgical system. METHODS: A
      retrospective clinical review was performed of ten patients with FIGO stage IA2
      IB1 cervical carcinoma who underwent a total robotic approach for definitive
      surgical treatment. Patient status was estimated in terms of operative morbidity,
      length of surgery, docking time, estimated blood loss, yield of pelvic lymph node
      and hospital stay. RESULTS: All operations were completed robotically with no
      conversions to laparotomy. Mean operative time was 207 min (range 120 to 240
      min). Mean docking time was 26 min (range 10 to 45 min). Mean estimated blood
      loss was 355 mL. The average number of pelvic lymph nodes resected was 27.6
      (range 12 to 52). There were no ureteral injuries or fistula complications.
      CONCLUSIONS: Robotic radical hysterectomy with pelvic lymphadenectomy for
      selected patients with stage IB1 cervical cancer is feasible, promising and
      related with a low morbidity in this pilot study. Only prospective randomized
      trials will permit the evaluation of potential benefits associated with this
      surgical technique.

PMID- 18035406
TI  - Laparoscopic surgery for early-stage endometrial cancers.

PMID- 18035408
TI  - Induction of pluripotent stem cells from adult human fibroblasts by defined
      factors.
AB  - Successful reprogramming of differentiated human somatic cells into a pluripotent
      state would allow creation of patient- and disease-specific stem cells. We
      previously reported generation of induced pluripotent stem (iPS) cells, capable
      of germline transmission, from mouse somatic cells by transduction of four
      defined transcription factors. Here, we demonstrate the generation of iPS cells
      from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2,
      Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells
      in morphology, proliferation, surface antigens, gene expression, epigenetic
      status of pluripotent cell-specific genes, and telomerase activity. Furthermore,
      these cells could differentiate into cell types of the three germ layers in vitro
      and in teratomas. These findings demonstrate that iPS cells can be generated from
      adult human fibroblasts.

PMID- 18035407
TI  - Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic,
      serotonergic and cholinergic neurons.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative and a
      popular drug of abuse that exhibits mild hallucinogenic and rewarding properties
      and engenders feelings of connectedness and openness. The unique
      psychopharmacological profile of this drug of abuse most likely is derived from
      the property of MDMA to promote the release of dopamine and serotonin (5-HT) in
      multiple brain regions. The present review highlights primarily data from studies
      employing in vivo microdialysis that detail the actions of MDMA on the release of
      these neurotransmitters. Data from in vivo microdialysis experiments indicate
      that MDMA, like most amphetamine derivatives, increases the release of dopamine
      in the striatum, n. accumbens and prefrontal cortex. However, the release of
      dopamine evoked by MDMA in each of these brain regions appears to be modulated by
      concomitantly released 5-HT and the subsequent activation of 5-HT2A/C or 5-HT2B/C
      receptors. In addition to its stimulatory effect on the release of monoamines,
      MDMA also enhances the release of acetylcholine in the striatum, hippocampus and
      prefrontal cortex, and this cholinergic response appears to be secondary to the
      activation of histaminergic, dopaminergic and/or serotonergic receptors. Beyond
      the acute stimulatory effect of MDMA on neurotransmitter release, MDMA also
      increases the extracellular concentration of energy substrates, e.g., glucose and
      lactate in the brain. In contrast to the acute stimulatory actions of MDMA on the
      release of monoamines and acetylcholine, the repeated administration of high
      doses of MDMA is thought to result in a selective neurotoxicity to 5-HT axon
      terminals in the rat. Additional studies are reviewed that focus on the
      alterations in neurotransmitter responses to pharmacological and physiological
      stimuli that accompany MDMA-induced 5-HT neurotoxicity.

PMID- 18035409
TI  - PKC signaling in oxidative hepatic damage.
AB  - Protein kinase C (PKC) is a family of isoenzymes differently involved in cell
      response to injury and many studies describe their role as "stress sensors".
      Oxidative stress is strictly involved in the pathogenesis of chronic liver
      diseases including alcohol- or drug-induced hepatotoxicity, iron overload,
      hepatitis and hepatocarcinoma development, but molecular mechanisms are not
      really defined. A crucial role of PKC as a redox sensitive signaling molecule has
      been widely accepted.

PMID- 18035410
TI  - The immobilization of proteins on biodegradable polymer fibers via click
      chemistry.
AB  - A facile and efficient method to immobilize bioactive proteins onto polymeric
      substrate was established. Testis-specific protease 50 (TSP50) was immobilized on
      ultrafine biodegradable polymer fibers, i.e., (1) to prepare a propargyl
      containing polymer P(LA90-co-MPC10) by introducing propargyl group into a cyclic
      carbonate monomer (5-methyl-5-propargyloxycarbonyl-1,3-dioxan-2-one, MPC) and
      copolymerizing it with l-lactide; (2) to electrospin the functionalized polymer
      into ultrafine fibers; (3) to azidize the TSP50, and (4) to perform the click
      reaction between the propargyl groups on the fibers and the azido groups on the
      protein. The TSP50-immobilized fibers can resist non-specific protein adsorptions
      but preserve specific recognition and combination with anti-TSP50. ELISA tests
      were carried out by using HRP-goat-anti-mouse-IgG(H+L) as secondary antibody and
      o-phenylenediamine (OPDA)/H(2)O(2) as substrate to detect the combination of
      immobilized TSP50 with anti-TSP50. The results showed that anti-TSP50 can be
      selectively adsorbed from its solution onto the TSP50-immobilized fibers in the
      presence of BSA of as high as 10(4) times concentration. TSP50 immobilized on the
      fiber and anti-TSP50 combined to the fiber were also quantitatively determined.
      Anti-TSP50 can be then eluted off from the fiber when pH changes. The eluted
      fiber can re-combine anti-TSP50 at an efficiency of 75% compared to the original
      TSP50-immobilized fiber. Therefore, the TSP50-immobilized fibers can be used in
      the detection, separation, and purification of anti-TSP50. The "click" method can
      lead to a universal strategy to protein immobilization.

PMID- 18035411
TI  - The effect of covalent cross-links between the membrane components of
      microcapsules on the dissemination of encapsulated malignant cells.
AB  - Stem cells and immortalized cells have considerable therapeutic potential but
      present risks of malignant transformation. Cell microencapsulation allows
      transplantation without immunosuppression. We have developed a method for
      microencapsulating living cells within covalently cross-linked membranes that are
      chemically and mechanically extremely resistant. We provide herein direct
      evidence that these microcapsules can prevent malignant cell dissemination. When
      20,000 or more nonencapsulated EL-4 thymoma cells were implanted
      intraperitoneally in mice, all recipients died with widespread metastasis within
      26.3+/-1.0 days. All recipients of 250,000 EL-4 cells microencapsulated in
      covalently cross-linked membranes were living and disease-free, 150 days post
      implantation. Encapsulation in standard microcapsules only slightly delayed the
      recipient death. Pancreatic islets transplanted using either type of microcapsule
      presented similar survival. We conclude that microencapsulation in covalently
      cross-linked membranes prevents malignant cell dissemination.

PMID- 18035413
TI  - Glutathione S-transferases (GSTT1 and GSTM1) genes polymorphisms and the
      treatment response and prognosis in Chinese patients with de novo acute myeloid
      leukemia.
AB  - We investigated the prognostic significance of genetic polymorphism for
      glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase mu 1
      (GSTM1) in 254 Chinese patients with de novo acute myeloid leukemia (AML) other
      than AML-M3. The early death rate after the initiation of chemotherapy was
      similar between the GSTT1+/GSTM1+ group and GSTT1-/GSTM1- group. The complete
      remission (CR) rate was higher in GSTM1+ group than in GSTM1- group (OR=1.88;
      P=0.03) after the first course of chemotherapy, and was higher in GSTT1+ group
      than in GSTT1- group (OR=2.20; P=0.02) after the second course of chemotherapy.
      Overall survival and disease-free survival of CR patients in GSTT1 and GSTM1
      double present group was better than in GSTT1- and/or GSTM1-group (P=0.03 and
      0.02, respectively). Our preliminary results warrant testing of a larger number
      of patients.

PMID- 18035412
TI  - Development of a tissue-engineered vascular graft combining a biodegradable
      scaffold, muscle-derived stem cells and a rotational vacuum seeding technique.
AB  - There is a clinical need for a tissue-engineered vascular graft (TEVG), and
      combining stem cells with biodegradable tubular scaffolds appears to be a
      promising approach. The goal of this study was to characterize the incorporation
      of muscle-derived stem cells (MDSCs) within tubular poly(ester urethane) urea
      (PEUU) scaffolds in vitro to understand their interaction, and to evaluate the
      mechanical properties of the constructs for vascular applications. Porous PEUU
      scaffolds were seeded with MDSCs using our recently described rotational vacuum
      seeding device, and cultured inside a spinner flask for 3 or 7 days. Cell
      viability, number, distribution and phenotype were assessed along with the suture
      retention strength and uniaxial mechanical behavior of the TEVGs. The seeding
      device allowed rapid even distribution of cells within the scaffolds. After 3
      days, the constructs appeared completely populated with cells that were spread
      within the polymer. Cells underwent a population doubling of 2.1-fold, with a
      population doubling time of 35 h. Stem cell antigen-1 (Sca-1) expression by the
      cells remained high after 7 days in culture (77+/-20% vs. 66+/-6% at day 0) while
      CD34 expression was reduced (19+/-12% vs. 61+/-10% at day 0) and myosin heavy
      chain expression was scarce (not quantified). The estimated burst strength of the
      TEVG constructs was 2127+/-900 mm Hg and suture retention strength was 1.3+/
      0.3N. We conclude from this study that MDSCs can be rapidly seeded within porous
      biodegradable tubular scaffolds while maintaining cell viability and high
      proliferation rates and without losing stem cell phenotype for up to 7 days of in
      vitro culture. The successful integration of these steps is thought necessary to
      provide rapid availability of TEVGs, which is essential for clinical translation.

PMID- 18035414
TI  - Prognostic significance of ATM and TP53 deletions in Chinese patients with
      chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common adult form of leukemia in
      the Western world, however, infrequent in the Eastern. It shows a remarkable
      heterogeneity, with some patients having an almost normal lifespan, others
      surviving only several years after diagnosis despite intensive therapy. To
      prospectively explore the prognostic significance of ATM and TP53 deletions in
      Chinese patients with CLL, interphase fluorescence in situ hybridization (FISH)
      and probes of LSI ATM and LSI p53 were used to detect ATM and TP53 deletions in
      95 patients with CLL. ATM and TP53 deletions and their association with some
      other prognostic factors such as Binet stage, lymphocyte count in peripheral
      blood, serum lactate dehydrogenase (LDH), beta2-microglobulin (beta2-MG), CD38
      and ZAP-70 expressions were analyzed. The Kaplan-Meier method was used to
      construct survival curves, and results were compared using the log-rank test.
      Univariate and multivariate Cox regression analyses were used to assess
      associations between survival time and potential risk factors. Out of the 95
      patients with CLL, ATM gene deletion was found in 9 (9.5%) patients, TP53 gene
      deletion in 16 (16.8%) cases. There were no significant differences between ATM
      or TP53 deletion and clinical parameters of sex, age, Binet stage, lymphocyte
      count, LDH, beta2-MG or ZAP-70 expression. However, the frequency of ATM and TP53
      deletions were obviously higher in CD38-positive group than in CD38-negative
      group (P=0.001 and P=0.047, respectively). Among 41 patients received treatment
      with fludarabine and cyclophosphamide, there were nine patients with TP53 or ATM
      deletion, and no patient with these cytogenetic abnormalities achieved complete
      response (CR). Survival analysis showed that the patients with TP53 deletion had
      significantly shorter survival times than the patients without TP53 deletion.
      There was no evidence of important association between outcome and ATM gene
      deletion. Serum levels of LDH and beta2-MG, CD38 expression, and TP53 deletion
      were the significant factors in determining overall survival (OS). TP53 deletion
      and CD38 expression were the variables strongly associated with OS by
      multivariate Cox regression analysis. It was showed that ATM or TP53 deletion is
      associated with high expression level of CD38 and TP53 deletion as a possible
      prognostic factor in Chinese patients with CLL.

PMID- 18035415
TI  - Men's self-definitions of abusive childhood sexual experiences, and potentially
      related risky behavioral and psychiatric outcomes.
AB  - OBJECTIVES: To estimate how many heterosexual and gay/bisexual men self-define
      abusive childhood sexual experiences (CSEs) to be childhood sexual abuse (CSA)
      and to assess whether CSA self-definition is associated with risky behavioral and
      psychiatric outcomes in adulthood. METHODS: In Philadelphia County, 197 (66%) of
      298 recruited men participated in a telephone survey. They were screened for CSEs
      and then asked if they self-defined abusive CSEs to be CSA; they also were asked
      about risk behavior histories and post-traumatic stress disorder (PTSD) and
      depression symptoms. RESULTS: Of 43 (22%) participants with abusive CSEs, 35% did
      not and 65% did self-define abusive CSEs to be CSA ("Non-Definers" and
      "Definers," respectively). Heterosexual and gay/bisexual subgroups' CSA self
      definition rates did not significantly differ. When self-definition subgroups
      were compared to those without CSEs ("No-CSEs"), Non-Definers had lower perceived
      parental care (p=.007) and fewer siblings (p=.03), Definers had more Hispanics
      and fewer African Americans (p=.04), and No-CSEs had fewer gay/bisexual men
      (p=.002) and fewer reports of physical abuse histories (p=.02) than comparison
      groups. Non-Definers reported more sex under the influence (p=.001) and a higher
      mean number of all lifetime sex partners (p=.004) as well as (only) female sex
      partners (p=.05). More Non-Definers than Definers reported having experienced
      penetrative sex as part of their CSA (83% vs. 35%, p=.006). Different
      explanations about self-definition were provided by subgroups. CONCLUSIONS: Many
      men with abusive CSEs do not self-define these CSEs to be CSA, though not in a
      way that differs by sexual identity. The process by which men self-define their
      abusive CSEs to be CSA or not appears to be associated not only with self
      explanations that differ by self-definition subgroup, but also with behavioral
      outcomes that impart risk to Non-Definers.

PMID- 18035416
TI  - Studies of the neural mechanisms of deep brain stimulation in rodent models of
      Parkinson's disease.
AB  - Several rodent models of deep brain stimulation (DBS) have been developed in
      recent years. Electrophysiological and neurochemical studies have been performed
      to examine the mechanisms underlying the effects of DBS. In vitro studies have
      provided deep insights into the role of ion channels in response to brain
      stimulation. In vivo studies reveal neural responses in the context of intact
      neural circuits. Most importantly, recording of neural responses to behaviorally
      effective DBS in freely moving animals provides a direct means for examining how
      DBS modulates the basal ganglia thalamocortical circuits and thereby improves
      motor function. DBS can modulate firing rate, normalize irregular burst firing
      patterns and reduce low frequency oscillations associated with the Parkinsonian
      state. Our current efforts are focused on elucidating the mechanisms by which DBS
      effects on neural circuitry improve motor performance. New behavioral models and
      improved recording techniques will aide researchers conducting future DBS studies
      in a variety of behavioral modalities and enable new treatment strategies to be
      explored, such as closed-loop stimulations based on real time computation of
      ensemble neural activity.

PMID- 18035417
TI  - A novel immunoglobulin-like transcript from rainbow trout with two Ig-like
      domains and two isoforms.
AB  - Within the innate immune response in primates the nonrearranging killer
      immunoglobulin-like receptors (KIR) enable natural killer cells to discern target
      cells exposing "missing self" signals. Recently the novel immune-type receptor
      (NITR) and the novel immunoglobulin-like transcript (NILT) gene families have
      been discovered in fish encoding nonrearranging receptors with a similar
      molecular structure to that of KIRs. Besides the structural similarity the high
      degree of haplotypic and allelic variation suggests these genes to be functional
      KIR homologs and involved in recognizing self-determinants in lower vertebrates.
      Whereas numerous NITR sequences have been detected in several fish species only
      two NILT genes have been published for carp yet. Here we report a first rainbow
      trout NILT sequence, Onmy-NILT2D, alternatively spliced into a long membrane
      bound and a short, putatively secreted form, both with the same two
      immunoglobulin (Ig)-like domains. The second Ig-like domain comprises a consensus
      pattern present both in NILTs and NITRs. The cytoplasmic region of the long form
      simultaneously contains immunoreceptor tyrosine-based inhibitory motifs (ITIM)
      and an immunoreceptor tyrosine-based activating motif (ITAM).

PMID- 18035418
TI  - A novel mimovirus vaccine containing survivin epitope with adjuvant IL-15 induces
      long-lasting cellular immunity and high antitumor efficiency.
AB  - Numerous evidences have indicated that CD8+ cytotoxic T lymphocytes (CTLs) played
      a significant role in protecting host against tumors, thus CTLs have been
      involved as potentially relevant candidate targets of cancer immunotherapy.
      Moreover it is crucial to fully elucidate antigen-specific CTL response,
      especially high-avidity and long-lasting CTL response in vivo. In the present
      study, we reported a novel tumor vaccine (mimovirus), a viron-size particulate
      which consisted of a cell-penetrating peptide of Tat(49-57), a CTL epitope
      peptide survivin(85-93) and a plasmid encoding murine interleukin-15 (IL-15). We
      demonstrated that this tumor vaccine could effectively mediate the expression of
      the gene and presentation of the tumor antigen derived peptide ex vivo.
      Furthermore, the tumor vaccine supported a robust memory CTL-mediated long-term
      immunity in vivo, which could effectively protect BALB/c mice against fatal CT26
      tumor challenge and improve their survival. These findings suggest that the tumor
      vaccine may provide an alternative therapeutic strategy for cancer patients.

PMID- 18035419
TI  - T cell receptor beta chain from sea bream (Sparus aurata): molecular cloning,
      expression and modelling of the complexes with MHC class I.
AB  - The T cell receptor is a fundamental mediator of the adaptive immune responses,
      since TR alphabeta on T cells recognize foreign structures (peptides derived from
      processed antigens) bound to the major histocompatibility complex (MHC) on APC
      cells. In the present study, we report the cloning of six TRB chains cDNA
      sequences from gilthead sea bream (Sparus aurata), a fish of high economical
      impact in South Mediterranean aquaculture. The V-BETA domains have the canonical
      features of known teleost and mammalian TR V-BETA domains and have been divided
      in four different subgroups. A multiple alignment of the six sea bream TRB chains
      with other known TRB sequences was assembled and showed the conservation of the
      four cysteine residues involved in disulphide bonds and of some amino acids with
      an important role in the assembly and signalling of the TR alphabeta/CD3 complex.
      Real-time PCR analysis was used to investigate TRB basal expression, that was
      maximum in the thymus followed by gut, and TRB in vitro expression after
      stimulation with LPS or PHA-L at 4 and 24h (only the 4h stimulation with LPS gave
      a significant effect). Moreover, the 3D structures of sea bream TRB chains and
      MHC-I were predicted by homology modelling with the final aim to investigate the
      interaction surface in the V-BETA/MHC-I complexes.

PMID- 18035421
TI  - Reaction of a model siderophore with Ni(II), Co(II) and Zn(II) in aqueous
      solution: kinetics and spectroscopy.
AB  - A spectroscopic study was performed showing that the [Fe(III)(L(2-))(2)](1-) (L(2
      )=dopacatecholate) complex reacts with Ni(II), Co(II) and Zn(II) in an aqueous
      solution containing S(2)O(3)(2-) resulting in the soluble [M(L(1-))(3)](1-) (L(1
      )=dopasemiquinone; M=Ni(II), Co(II) or Zn(II) complex species. The Raman and IR
      spectra of the [CTA][M(L(1-))(3)] complexes, CTA=hexadecyltrimethylammonium
      cation, in the solid state were obtained. The kinetic constants for the metal
      substitution reactions were determined at four different temperatures, providing
      values for DeltaH(not equal), DeltaS(not equal) and DeltaG(not equal). The
      reactions were slow (k=10(-11) Ms(-1)) and endothermic. The system investigated
      can be considered as a simplified model to explain some aspects of siderophore
      chemistry.

PMID- 18035420
TI  - Temporal effects of newly developed oximes (K027, K048) on malathion-induced
      acetylcholinesterase inhibition and lipid peroxidation in mouse prefrontal
      cortex.
AB  - The potency of newly developed asymmetric bispyridinium oximes (K027, K048) in
      reactivating acetylcholinesterase and in eliminating oxidative stress induced by
      acute exposure to malathion was evaluated in mouse prefrontal cortex using in
      vivo methods. Malathion (1g/kg, dissolved in saline) was administered
      subcutaneously. The asymmetric bispyridinium oximes K027 or K048 (1/4 of LD(50),
      dissolved in saline, i.p.) were administered immediately after malathion and
      atropine sulfate (20mg/kg, dissolved in saline, i.p.). Control group received
      saline instead of malathion and antidotes. Acetylcholinesterase activity and
      biochemical parameters related to oxidative stress (glutathione levels,
      glutathione peroxidase and glutathione reductase activity and lipid peroxidation)
      were evaluated in mouse prefrontal cortex at two different time points (3 or 24 h
      after malathion poisoning). Malathion administration markedly inhibited cortical
      acetylcholinesterase activity (around 55%) at 3h after malathion challenge and
      such inhibition was maintained till 24 h after poisoning. Although neither
      atropine sulfate nor oximes were able to eliminate cortical acetylcholinesterase
      inhibition at 3h after malathion poisoning, K027 (in combination with atropine)
      completely eliminated the inhibitory effect of malathion exposure on cortical
      acetylcholinesterase activity at 24 h after malathion administration. K048 (in
      combination with atropine) significantly decreased acetylcholinesterase
      inhibition at 24 h after malathion poisoning. Even though glutathione levels and
      glutathione peroxidase and glutathione reductase activities were not affected,
      malathion administration markedly increased lipid peroxidation in the prefrontal
      cortex at 24 h after poisoning and the oxime K027 (in combination with atropine)
      was able to significantly decrease such phenomenon. Thus, our results clearly
      demonstrate that the newly developed asymmetric bispyridinium oximes K027 and
      K048 are able to reverse malathion-induced acetylcholinesterase inhibition in
      mouse prefrontal cortex. Moreover, the ameliorative effect of the oxime K027 on
      the increased lipid peroxidation observed at 24 h after malathion poisoning
      suggests a potential link between the hyperstimulation of cholinergic system and
      oxidative stress in the mouse prefrontal cortex after malathion exposure.

PMID- 18035422
TI  - Two-month-olds' attention and affective response to maternal still face: a
      comparison between term and preterm infants in Taiwan.
AB  - Maternal still face is a robust experimental procedure designed to examine
      infants' sensitivity to social contingency and reactivity to its violation. To
      extend earlier research on the still-face effect on term infants in Western
      cultures, the present study compared Taiwanese term and preterm infants'
      attention and affective response to and recovery from a modified maternal still
      face procedure that used an additional still-face reengagement sequence at 2
      months of age (corrected age for preterm infants). Infants' gaze and facial
      affect were coded from videos. Results showed that preterm infants were as
      sensitive as term infants to the interruption to social contingency. Both groups
      of infants reacted with decreased gaze and positive affect across episodes,
      together with a decreased latency to gaze aversion and an increased latency to
      positive affect. Both term and preterm infants also demonstrated a W-shaped
      pattern of decline-followed-by-recovery in their latency to negative affect.
      However, compared to term infants, preterm infants became distressed faster and
      stayed in a negative affective state longer after the first exposure to maternal
      still face. Effects of prematurity on infant attention and affect regulation were
      discussed. Implications of preterm infants' heightened affective negativity to
      mild stress for intervention studies were also addressed.

PMID- 18035423
TI  - Neuroprotection by pravastatin in acute ischemic stroke in rats.
AB  - Pleiotropic mechanisms beyond their cholesterol lowering effect of 3-hydroxy 3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins such as
      pravastatin are known. We used a temporary middle cerebral artery occlusion
      (tMCAO) model in 114 Wistar rats to assess i) whether repeated injections of
      various doses of pravastatin (0.1, 0.5, 1 and 2 mg/kg) at 30 min, 6 h, 1, 2, 3,
      and 4 days after stroke onset are neuroprotective, ii) whether attenuation of
      striatal glutamate and interleukin-6 (IL-6) release is part of the
      neuroprotective mechanism, and iii) how local cerebral blood flow (CBF) is
      influenced by pravastatin both in the acute and late stage of ischemia. Animals
      were sacrificed 5 days after MCAO, infarct size was analyzed with 2,3,5
      triphenyltetrazolium chloride (TTC) staining. As compared to saline (139+/-14
      mm3, n=11), higher doses of pravastatin beyond 0.1 mg/kg significantly reduced
      infarct size with the greatest effect obtained with 1 mg/kg (60+/-14 mm3, n=11,
      P=0.0004). Using cerebral microdialyis in this dose group, we demonstrated that
      striatal glutamate increase in the ischemic hemisphere was attenuated by
      pravastatin compared to placebo. Likewise, IL-6 release was diminished at 2 h,
      but not at 6 h after tMCAO. Improvement of local CBF by pravastatin was observed
      at day 5, but not at 5 h after tMCAO, thus representing a more long term effect
      of pravastatin. In conclusion, a relatively high dose of pravastatin administered
      repetitively after stroke onset improved neurological outcome through various
      cholesterol-independent mechanisms.

PMID- 18035425
TI  - The role of CTLA-4 in immune regulation.

PMID- 18035424
TI  - Detection of full-length and truncated neurokinin-1 receptor mRNA expression in
      human brain regions.
AB  - We have applied a newly developed SYBR green-based real-time RT-PCR assay for
      quantification of full-length and truncated neurokinin-1 receptor (NK1R) mRNA
      expression in nine regions of human brain tissues obtained from 23 subjects who
      died with no evidence of neurological or neurodegenerative disease. The following
      brain regions were examined: cingulate cortex, cerebellum, nucleus accumbens,
      caudate nucleus, putamen, pons, hippocampus, locus coeruleus, and basal ganglia.
      The SYBR green-based real-time PCR was more sensitive than TaqMan probe-based
      real-time PCR in amplifying both full-length and truncated NK1R mRNA. The real
      time RT-PCR assay had excellent specificity and sensitivity, with a dynamic range
      of detection between 100 and 1,000,000 copies of the NK1R cDNA per reaction. The
      truncated NK1R mRNA levels were more abundant than those of the full-length NK1R
      in most of the regions examined and there was no significant difference in the
      truncated NK1R mRNA levels among the nine regions studied. There was, however, a
      significant difference in the expression of full-length NK1R mRNA levels among
      the nine regions (P=0.0024), and the putamen region expressed the highest full
      length NK1R mRNA. Further studies are needed in order to examine the differences
      between full-length and truncated NK1R in signal transduction and functional
      consequences in order to delineate the significance of the co-presence of the two
      forms of NK1R in the human brain.

PMID- 18035426
TI  - Exercise with latex sport bands represents a risk for latex allergic patients.
AB  - Based on two clinical observations of adverse reactions during exercise with
      latex sport bands, we aimed to assess the possible risk for allergic patients
      posed by this equipment by investigating allergen content and IgE binding
      potential. Protein extracts of three different latex sport bands were
      characterized with sera of latex allergic patients. The IgE recognition profile
      of the allergic patients was identified by component resolved diagnosis and the
      allergen composition of the extracts was characterized by inhibition assays with
      the recombinant latex allergens Hev b 1, 3, 5, 6.02, and 8. The sera showed
      pronounced IgE binding to all three blotted extracts, however with diverse
      patterns. Inhibition assays revealed the presence of Hev b 1, 3, 5, and 8 in
      latex sport band extracts. The clinical relevance of contained allergens was
      demonstrated by strong skin reactions when testing with latex sport bands. From
      our results we conclude that latex sport bands contain clinically relevant
      allergens and may cause latex allergic individuals to experience allergic
      symptoms, potentially amplified by exercise-induced mechanisms. Even though latex
      is labeled on products, it is important that patients as well as athletic
      trainers and physical therapists recognize the risk of adverse reactions with
      these bands.

PMID- 18035427
TI  - Pharmacokinetics of CIPRODEX otic in pediatric and adolescent patients.
AB  - OBJECTIVE: Describe the pharmacokinetics of ciprofloxacin and dexamethasone after
      administration of CIPRODEX Otic Suspension (CIP/DEX) into the middle ears of
      children. DESIGN: Open-label, single-dose, pharmacokinetic studies, administering
      four drops of CIP/DEX instilled into each middle ear through the tympanostomy
      tubes immediately following tube placement. Blood was collected for 6h and
      analyzed for ciprofloxacin and dexamethasone concentrations using a validated
      liquid chromatography and tandem mass spectrometry (LC/MS/MS) method. SETTING:
      The study was conducted through a referral pediatric otolaryngology practice with
      actual surgical procedures performed in an ambulatory care center. PATIENTS:
      Twenty-five randomly selected patients, 1-14 years of age (mean age, 5 years),
      receiving tympanostomy tubes. RESULTS: Peak ciprofloxacin plasma levels were
      observed at about 1h, with a mean C(max) of 1.33+/-0.96 ng/mL (range <0.5-3.45
      ng/mL) and an estimated half-life of 3.0+/-1.2h. Peak dexamethasone plasma levels
      were observed within 2h with a mean C(max) of 0.90+/-1.04 ng/mL (range <0.05-5.10
      ng/mL) and an estimated half-life of 3.9+/-2.9h. CONCLUSION: These results
      demonstrated low systemic exposure of ciprofloxacin and dexamethasone following
      topical otic administration in pediatric patients.

PMID- 18035428
TI  - Potential of antiviral therapy and prophylaxis for controlling RNA viral
      infections of livestock.
AB  - With intensification of trade, livestock are increasingly exposed to severe
      animal diseases caused by a range of RNA viruses. Recent prime examples include
      outbreaks of foot-and-mouth disease (FMD), peste des petits ruminants, Rift
      Valley fever and bluetongue. To minimise their impact, controlling the spread of
      virus is of utmost importance. Good quality, reliable vaccines exist for some,
      although not all, of these diseases, but suffer from a set of drawbacks, not the
      least of which being the time needed to trigger the immune response (i.e.
      "immunity-gap"). Effective, rapid control tools are, therefore, urgently needed
      and antiviral compounds could serve this purpose. Although limited in vitro and
      in vivo research has been performed, encouraging results for FMD suggest that
      livestock could be protected against infection within 24h following antiviral
      treatment and up to 12h post-infection. Such prophylactic/therapeutic antiviral
      drugs could complement emergency vaccination in a previously disease-free setting
      or be applied to treat valuable zoological collections and breeding stocks in
      endemic and previously disease-free regions alike. This paper will primarily
      focus on the effects of FMD on livestock and other sectors, and on appropriate
      control tools. The outlined principles can be extrapolated to other RNA viral
      diseases.

PMID- 18035429
TI  - Neural correlates to both emotion and cognitive functions in the monkey amygdala.
AB  - Recent lesion and non-invasive studies identify the medial temporal lobe,
      including the amygdala, not only with emotion but also with working memory in
      relation to the prefrontal cortex. In the present study, amygdalar neuronal
      activity was recorded from monkeys during performance of discrimination tasks
      that led to presentation of emotion-related (rewarding or aversive) stimuli. The
      task had three phases: (1) discrimination (visual, auditory), (2) operant
      response (bar pressing) and (3) ingestion (reward) or avoidance (aversion). These
      neurons were further analyzed by a short-term memory task, delayed pair
      comparison (DPC) using colored lamps. Of 585 amygdalar neurons, 107 responded
      primarily to single sensory stimulation (40 vision related, 26 audition related,
      41 ingestion related), 117 to multimodal stimulation (multimodal) and 14
      responded selectively to only one item (selective). Of 417 neurons tested by the
      DPC, 122 responded in one or more phases. Of these 122 neurons, 10.7% responded
      in the delay period. These delay-responsive neurons also responded to various
      objects with positive and negative affective significance. These results suggest
      that amygdalar neurons are not specifically related to working memory, as are
      those in the inferotemporal and prefrontal cortices, but are related to more
      general non-specific functions or processes such as arousal or attention during
      the cognitive tasks. A functional role of the amygdala in working memory is
      discussed in terms of recent non-invasive studies suggesting a functional
      coupling between the amygdala and prefrontal cortex.

PMID- 18035430
TI  - Method of recruitment and the scores of self-report measures: the example of
      worry in the elderly.
AB  - Due to the difficulties in recruiting elderly people for psychological studies, a
      wide range of recruitment methods has been used. The underlying assumption that
      the recruitment method does not seriously affect the results has to be tested.
      Results in different worry measures are compared between three samples which were
      recruited with different strategies: (i) randomization sampling from the census
      of an urban area (random sample; n=97); (ii) people involved in leisure
      activities in senior centers (convenience sample; n=142); and (iii) people from
      the close environment of psychology students (snowball sample; n=60). People from
      those samples, aged 65 and more, completed the Penn State Worry Questionnaire
      (trait-worry), and the Worry Scale (contents of worry). Differences were found
      for several demographic characteristics. There were marked differences between
      samples in the percentage of individuals endorsing cut-score criteria for
      generalized anxiety disorder (GAD), with a very high percentage for the snowball
      sample. For all of the worry measures, analyzes of variance revealed
      significantly higher total scores for the non-randomly selected samples (p<0.01).
      Comparing the latter samples, higher trait worry (p<0.01) and more worrying about
      health and personal competencies (p<0.01) was found in the snowball sample. These
      results suggest that the sample recruitment method can specifically and seriously
      affect the outcomes of studies with elderly people, thus limiting the
      generalization of their results.

PMID- 18035431
TI  - Transient mid-ventricular dyskinesia: a variant of Takotsubo syndrome.
AB  - Takotsubo Cardiomyopathy is characterized by a reversible systolic left
      ventricular apical ballooning. A new pattern of dyskinesia in the absence of
      angiographic evidence of coronary artery stenosis has been indicated like a
      variant of takotsubo cardiomiopathy: mid-ventricular akinesis with preservation
      of apical and basal contractilities revealed at echocardiograms and
      ventriculographies. We report the case of a 65 years old patient with this
      pattern, reverted in 4 weeks.

PMID- 18035432
TI  - Early electrocardiographic diagnosis of acute coronary ischemia on the paced
      electrocardiogram.
AB  - BACKGROUND: Twelve-lead electrocardiography (ECG) is the most important source
      for the early diagnosis of an acute myocardial ischemia. However, its diagnostic
      value when the sequence of ventricular activation is altered by ventricular
      pacing is unknown. The aim of the study was to evaluate the ECG changes on the
      paced ECG during percutaneous coronary intervention (PCI) by doing temporary
      pacing. METHODS AND RESULTS: Standard 12 lead baseline and temporary pacing ECG
      records were taken before the intervention in elective PCI patients. Standard 12
      lead and temporary pacing ECG records were repeated during the balloon inflation.
      Fifteen (12 men and 3 women; age 57.2+/-9.7 years) subjects who were undergoing
      routine PCI were studied. Mean Delta ST deviation on the normal conduction ECG
      during inflation was 1.03+/-1.02 mV and mean Delta ST deviation on the paced ECG
      during inflation was 1.7+/-1.6 mV. The pre-inflation mean QRS duration on the
      paced ECG was 143.2+/-2.8 ms and during inflation mean QRS duration was 157.8+/
      12.5 ms. The mean QRS prolongation was 14.6+/-13.6 ms on the paced ECG. Despite
      the presence of paced ECG abnormalities, significant ischemic ST segment
      deviations were seen after referencing the ST segment deviations to the pre-PCI.
      Also, there is significant QRS prolongation on the paced ECG during ischemia.
      CONCLUSIONS: The present study extends the correlation between normal and paced
      ECG during ischemia and the QRS prolongation could be a marker of myocardial
      ischemia on the paced electrocardiogram.

PMID- 18035433
TI  - Chronic heart failure and chronic obstructive pulmonary disease: one problem, one
      solution?
AB  - Chronic heart failure and chronic obstructive pulmonary disease are both
      increasing in prevalence throughout the developed world. Despite new therapies
      especially for chronic heart failure, morbidity and mortality rates for both
      conditions remain high. This editorial highlights the skeletal myopathy that has
      been recognised in both diseases, and its central role in exercise limitation.
      Exercise training has been shown to benefit the myopathy, functional capacity and
      also survival, again in both conditions. Exercise training is now established in
      the guidelines for both diseases in the developed world and some reasons are
      suggested why its implementation has so far been limited especially for heart
      failure. In view of its effectiveness as a therapy, the failure to apply these
      guidelines should be addressed.

PMID- 18035434
TI  - Quadricuspid aortic valve: an unusual echocardiographic finding and a review of
      the literature.
AB  - This case report presents a rare clinical finding of an isolated quadricuspid
      aortic valve in an otherwise healthy 24-year-old female who was referred for
      cardiac evaluation due to newly identified murmur. A transthoracic echocardiogram
      suggested an unusual case of a bicuspid aortic valve with two raphes with normal
      opening and mild aortic regurgitation. This case exemplified that caution should
      be taken when encountering circumstances like the one presented, as the aortic
      valve anatomy might be mistaken based on a new proposed classification for
      bicuspid aortic valves recently published. Further evaluation identified the
      presence of a quadricuspid aortic valve using computer tomography of the chest.
      Care should be taken in evaluating aortic valves as in this case. The literature
      regarding quadricuspid aortic valves is reviewed.

PMID- 18035435
TI  - Clinical implications of the effects of non-ionic radiocontrast medium exposure
      on microalbuminuria in patients undergoing coronary angiography.

PMID- 18035436
TI  - Entrapment of a floating thrombus in the right atrium by persistent Chiari's
      network: a barrier to massive pulmonary embolism.
AB  - Syncope may be a manifestation of pulmonary embolism. Occlusion of a pulmonary
      artery with cardiac output drop, sometimes resulting in cardiac arrest, is the
      main underlying mechanism. In this letter we describe the case of a patient in
      which the persistence of a long remnant of the embryonal Chiari's network could
      have worked as an anatomic barrier preventing massive pulmonary embolism and
      cardiac arrest.

PMID- 18035437
TI  - Impact of periprocedural myonecrosis on clinical events after implantation of
      drug-eluting stents.
AB  - BACKGROUND: High level of creatine kinase myocardial band isoenzyme (CK-MB)
      elevation has been associated with late mortality after coronary intervention. We
      sought to evaluate the impact of periprocedural myonecrosis on clinical events in
      patients undergoing drug-eluting stents (DES) implantation. METHODS: A total of
      1807 patients (2550 lesions) with successful DES implantation were followed for
      mean duration of 13 + or - 7 months. Patients with acute myocardial infarction
      and those with elevated CK-MB at baseline were excluded. Based on the CK-MB
      levels after stenting, patients were classified into three groups: group I:
      normal CK-MB (n=1429, 79.1%), group II: 1 to 5 times normal CK-MB (n=263, 14.6%),
      and group III: >5 times normal CK-MB (n=115, 6.4%). Major adverse cardiac events
      (MACE) were defined as cardiac death, myocardial infarction, and target lesion
      revascularization. RESULTS: With increasing levels of periprocedural CK-MB, there
      was an increased incidence of MACE (5.0% in group I vs. 6.1% in group II vs.
      10.4% in group III, p=0.010) and cardiac death (0.5% in group I vs. 1.1% in group
      II vs. 2.6% in group III, p=0.016). By multivariate analysis, periprocedural peak
      CK-MB level was independent predictor of MACE (hazard ratio 1.01, 95% confidence
      interval 1.00 to 1.03; p=0.044). CONCLUSIONS: Periprocedural myonecrosis was
      significantly associated with subsequent adverse clinical events after DES
      implantation.

PMID- 18035438
TI  - The relationship between BNP and E/Ea in patients hospitalized with acute heart
      failure.
AB  - BNP and echocardiographic E/Ea are variables helpful in the management of
      patients with heart failure (HF). The response of E/Ea to treatment for acute
      decompensated HF remains uncertain. This pilot study aimed to explore this
      relationship. 24 patients (17 male, mean age 69 years, median ejection fraction
      26%) hospitalized with HF were enrolled in this study. Paired clinical
      examination, BNP-32 level, and echocardiogram were performed at admission and
      discharge. By discharge patient symptoms and BNP-32 had significantly improved,
      however E/Ea did not change. Our data suggests that BNP-32 and E/Ea may not be
      interchangeable indices and may respond differently during treatment of acute
      decompensated HF.

PMID- 18035439
TI  - Left main coronary artery stenting in a patient with acute myocardial infarction
      and cardiogenic shock.
AB  - Acute total occlusion of left main coronary artery (LMCA) is rarely found in
      patients presenting with acute coronary syndromes. It is a grave condition with
      poor prognosis. We present a case of successful stenting of a LMCA lesion in a
      patient presenting with acute myocardial infarct and cardiogenic shock.

PMID- 18035440
TI  - High grade glioma: imaging combined with pathological grade defines management
      and predicts prognosis.
AB  - INTRODUCTION: There is ambiguity in pathological grading of high grade gliomas
      within the WHO 2000 classification, especially those with predominant
      oligodendroglial differentiation. PATIENTS AND METHODS: All adult high grade
      gliomas treated radically, 1996-2005, were assessed. Cases in which pathology was
      grade III but radiology suggested glioblastoma (GBM) were classified as 'grade
      III/IV'; their pathology was reviewed. RESULTS: Data from 245 patients (52 grade
      III, 18 grade III/IV, 175 GBM) were analysed using a Cox Proportional Hazards
      model. On pathology review, features suggestive of more aggressive behaviour were
      found in all 18 grade III/IV tumours. Oligodendroglial components with both
      necrosis and microvascular proliferation were present in 7. MIB-1 counts for the
      last 8 were all above 14%, mean 27%. Median survivals were: grade III 34 months,
      grade III/IV 10 months, GBM 11 months. Survival was not significantly different
      between grade III/IV and GBM. Patients with grade III/IV tumours had
      significantly worse outcome than grade III, with a hazard of death 3.7 times
      higher. CONCLUSIONS: The results highlight the current inconsistency in
      pathological grading of high grade tumours, especially those with
      oligodendroglial elements. Patients with histological grade III tumours but
      radiological appearances suggestive of GBM should be managed as glioblastoma.

PMID- 18035442
TI  - Tumor specific ultrasound enhanced gene transfer in vivo with novel liposomal
      bubbles.
AB  - Bubble liposomes (liposomes which entrap an ultrasound imaging gas) may
      constitute a unique system for delivering various molecules efficiently into
      mammalian cells in vitro. In this study, Bubble liposomes were compared with
      cationic lipid (CL)-DNA complexes as potential gene delivery carriers into tumor
      in vivo. The delivery of genes by Bubble liposomes depended on the intensity of
      the applied ultrasound. Transfection efficiency plateaued at 0.7 W/cm(2)
      ultrasound intensity. Bubble liposomes efficiently transferred genes into
      cultured cells even when the cells were exposed to ultrasound for only 1 s. In
      addition, Bubble liposomes could introduce the luciferase gene more effectively
      than CL-DNA complexes into mouse ascites tumor cells and solid tumor tissue. We
      conclude that the combination of Bubble liposomes and ultrasound is a minimally
      invasive and tumor specific gene transfer method in vivo.

PMID- 18035441
TI  - Exploitation of the S-layer self-assembly system for site directed immobilization
      of enzymes demonstrated for an extremophilic laminarinase from Pyrococcus
      furiosus.
AB  - A fusion protein based on the S-layer protein SbpA from Bacillus sphaericus CCM
      2177 and the enzyme laminarinase (LamA) from Pyrococcus furiosus was designed and
      overexpressed in Escherichia coli. Due to the construction principle, the S-layer
      fusion protein fully retained the self-assembly capability of the S-layer moiety,
      while the catalytic domain of LamA remained exposed at the outer surface of the
      formed protein lattice. The enzyme activity of the S-layer fusion protein
      monolayer obtained upon recrystallization on silicon wafers, glass slides and
      different types of polymer membranes was determined colorimetrically and related
      to the activity of sole LamA that has been immobilized with conventional
      techniques. LamA aligned within the S-layer fusion protein lattice in a periodic
      and orientated fashion catalyzed twice the glucose release from the laminarin
      polysaccharide substrate in comparison to the randomly immobilized enzyme. In
      combination with the good shelf-life and the high resistance towards temperature
      and diverse chemicals, these novel composites are regarded a promising approach
      for site-directed enzyme immobilization.

PMID- 18035443
TI  - Drug incorporation and release of water soluble drugs from novel functionalized
      poly(glycerol adipate) nanoparticles.
AB  - We have previously demonstrated the ability of poly(glycerol adipate) backbone
      (PGA) and PGA polymer backbone substituted with varying amounts of pendant C(18)
      chain length acyl groups to yield Dexamethasone phosphate DXMP loaded
      nanoparticles. The aim of this study was to obtain a deeper understanding of the
      underlying principles responsible for good drug incorporation and controlled
      release of drugs from poly (glycerol adipate) (PGA) nanoparticles. We compared
      the incorporation of the water soluble drugs DXMP and Cytosine arabinoside (CYT
      ARA) in both unmodified and substituted PGA polymers. We investigated the effect
      of change in acyl group chain length and the degree of substitution on the
      physicochemical properties, drug loading and release of DXMP and CYT-ARA.
      Nanoparticles were prepared by the interfacial deposition technique and the
      simultaneous emulsification method. Amongst the nanoparticles prepared using
      acylated polymers with varying chain lengths (C(2) to C(10)) for DXMP
      incorporation, polymers with acyl group chain lengths containing 8 carbon atoms
      (C(8)) showed maximum drug incorporation. Amongst the C(8) series, polymers with
      100% acylation provided both good drug incorporation and a controlled release for
      DXMP while for CYT-ARA it was the unsubstituted polymer backbone that had maximum
      drug loading and slower release. A number of inter-related factors are
      responsible for producing particles with particular size, zeta potential, drug
      loading and release characteristics. Drug loading and release from nanoparticles
      are primarily influenced by the nature of interactions between the drug and
      polymers which in turn depend upon the type of drug used and the physical
      chemistry of the polymer.

PMID- 18035444
TI  - Coverage and predictors of influenza vaccination among adults with diabetes in
      Spain.
AB  - Based on data drawn from the 2003 National Health Survey (NHS), we sought to: (1)
      estimate influenza vaccination coverages among Spanish diabetic adults; (2)
      analyze which sociodemographic, health-related, and use of health-care services
      variables were associated with the likelihood of Spanish diabetes sufferers being
      vaccinated; and (3) analyze the time-trend in coverage for the period 2001-2003.
      We analyzed data on the 1295 adults suffering diabetes included in the 2003 NHS.
      The reply to the question "Were you vaccinated against influenza in the last
      vaccination campaign?" was taken as the dependent variable. Vaccination coverage
      was calculated and the influence of sociodemographic, health-related, and use of
      health-care services variables assessed. The proportion of vaccinated diabetic
      adults in 2003 amounted to 57%. Multivariate adjustment showed that the variables
      which increased the likelihood of being vaccinated were: higher age; male gender;
      presence of respiratory or heart diseases; and physician visits in the last 2
      weeks. Influenza coverages had significantly increased from 2001 (48.8%) to 2003.
      We conclude that influenza vaccination coverages among Spanish diabetic adults
      have improved but still remain below desirable levels and, thereby making it
      necessary for strategies to be implemented aimed at improving the use of
      influenza vaccine among diabetic patients, especially those less than 50 years,
      females and without other chronic conditions.

PMID- 18035445
TI  - Plasma relaxin concentration is related to beta-cell function and insulin
      sensitivity in women with type 2 diabetes mellitus.
AB  - We conducted a study to examine an association between relaxin, insulin
      sensitivity and beta-cell function in women with type 2 diabetes. Relaxin
      concentration was measured in plasma in 63 newly diagnosed women with type 2
      diabetes. We also measured body mass index (BMI), blood pressure, parameters of
      metabolic control (fasting glucose level, HbA1c, total, HDL and LDL cholesterol,
      triglycerides) and insulin resistance according to the homeostasis model
      assessment index 2 (HOMA2). Relaxin was positively related to insulin sensitivity
      (R=0.316 and p=0.01) and negatively to beta-cell (-0.382 and p=0.004) function.
      Logistic regression analysis revealed that the correlation between relaxin and
      HOMA2%B remained significant after adjustment for age, BMI (R(2)=0.253 and
      p=0.006). Our data raise the possibility that a gender-related hormonal mechanism
      may influence beta-cell function in women with type 2 diabetes.

PMID- 18035446
TI  - Improvements in the safety of patient care can help end the medical malpractice
      crisis in the United States.
AB  - The publication of To Err is Human: Building a Safer Health System by the
      Institute of Medicine (IOM) in 1999 made the general public aware of the large
      number of patients that suffer preventable medical injuries in hospitals
      throughout the United States. Improvements in patient safety are needed to reduce
      this high incidence of medical error and must include the establishment of a
      culture of safety in every healthcare facility. A culture of safety is
      characterized by honesty, transparent error communication, and a systems analysis
      approach to medical error prevention. This type of medical culture can serve as
      the foundation for sustained improvements in patient safety and will help provide
      permanent relief from the medical malpractice crisis. Health policymakers should
      create policies that encourage hospital executives to establish and maintain
      cultures of safety in their institutions.

PMID- 18035447
TI  - Inequalities in oral health practices and social space: an exploratory
      qualitative study.
AB  - This study analyzed the oral health practices and access to dental care of
      individuals according to their position in social space. The rationale was based
      on the hypothesis that different positions in social space may imply different
      habitus, in the sense conferred by Bourdieu. Such dispositions would influence
      practical behavior, choices and preferences in general and in this context,
      dental care. Twenty-two semi-structured interviews were carried out with
      individuals, as part of a multiple case study carried out in two municipalities
      in the state of Bahia, Brazil. Differences were found between the two study
      groups both with respect to actions of personal care and in seeking and using
      dental services. This, in addition to poor material and living conditions, and
      difficult access to restorative dental work in the public sector, may explain
      part of the pattern of tooth loss found in the adult Brazilian population. The
      adoption of effective communicative and educational actions by health
      professionals should be stimulated. However, the structural dimension of the
      social determinants requires transformations in the structures that generate the
      perceptions and practices of agents. The study discusses the implications of
      these data to public dental policies that are focused on reducing these
      inequalities.

PMID- 18035448
TI  - Hospital performance: competing or shared values?
AB  - OBJECTIVE: To find out which are the emerging views on hospital performance and
      to analyze how these views vary among hospital stakeholders. METHODS:  STUDY
      SETTING: Three hospital stakeholder groups (physicians, caregivers, and
      administrative staff) in a large Paris teaching hospital. STUDY DESIGN: A case
      study combining a qualitative (interviews of 80 key hospital stakeholders and a
      survey of hospital staff), and a quantitative analysis (a questionnaire composed
      of 4 theoretical dimensions, 13 sub-dimensions, 66 items) with triangulation of
      the results. RESULTS: Hospital stakeholders assign greatest importance to the
      human relations dimension, i.e., organizational climate (professional and public
      service values) and quality of work life. These values attract a high degree of
      consensus among stakeholders (no statistical difference between physicians,
      caregivers and administrative staff). CONCLUSIONS: Our findings challenge the
      mainstream view that competing values underlie hospital performance. Currently,
      views are to some extent shared among different stakeholder groups. A reason for
      this could be the need to form a more united front in the face of recent reforms.
      This common emphasis on professional and public service values could be the basis
      for formulating management priorities in teaching hospitals in order to improve
      performance.

PMID- 18035450
TI  - Calcium dysregulation in Alzheimer's disease.
AB  - Alzheimer disease (AD) is the most common form of adult dementia. Its
      pathological hallmarks are synaptic degeneration, deposition of amyloid plaques
      and neurofibrillary tangles, leading to neuronal loss. A few hypotheses have been
      proposed to explain AD pathogenesis. The beta-amyloid (Abeta) and
      hyperphosphorylated tau hypotheses suggest that these proteins are the main
      players in AD development. Another hypothesis proposes that the dysregulation of
      calcium homeostasis may be a key factor in accelerating other pathological
      changes. Although Abeta and tau have been extensively studied, recently published
      data provide a growing body of evidence supporting the critical role of calcium
      signalling in AD. For example, presenilins, which are mutated in familial cases
      of AD, were demonstrated to form low conductance calcium channels in the ER and
      elevated cytosolic calcium concentration increases amyloid generation. Moreover,
      memantine, an antagonist of the NMDA-calcium channel receptor, has been found to
      have a beneficial effect for AD patients offering novel possibilities for a
      calcium signalling targeted therapy of AD. This review underscores the growing
      importance of calcium ions in AD development and focuses on the relevant aspects
      of calcium homeostasis.

PMID- 18035451
TI  - Structure-activity relationships of sandalwood odorants: total synthesis and
      fragrance properties of cyclopropano-beta-santalol.
AB  - The synthesis and odor properties of cyclopropano-beta-santalol, a new santalol
      analogue, are described. The exocyclic double bond of the original molecule, beta
      santalol, is replaced by a cyclopropane ring. Despite the analogies in the
      binding properties between the double bond and cyclopropane this change in the
      bulky hydrophobic part of the molecule leads to the complete loss of the
      characteristic sandalwood odor: in an olfactory evaluation the (Z)-product
      appears spicy and sweet, the (E)-isomer woody, but neither of them exhibits the
      typical sandalwood character.

PMID- 18035449
TI  - TGF beta 1 and TNF alpha potentiate nitric oxide production in astrocyte cultures
      by recruiting distinct subpopulations of cells to express NOS-2.
AB  - Nitric oxide (NO) synthase-2 (NOS-2), a key source of NO at sites of
      neuroinflammation, is induced in astrocyte cultures treated with
      lipopolysaccharide (LPS) plus interferon-gamma (IFN gamma). A recent study
      examining the regulation of astrocytic NOS-2 expression demonstrated that
      transforming growth factor-beta1 (TGF beta 1) potentiated LPS plus IFN gamma
      induced NOS-2 expression via expansion of the pool of astrocytes that express NOS
      2. Results in the current report indicate that this population-based mechanism of
      increasing NOS-2 expression is not restricted to TGF beta 1, since it also
      accounts for the potentiation of NO production in astrocyte cultures by tumor
      necrosis factor-alpha (TNFalpha). In contrast to TGF beta 1, which required 24h
      preincubation for optimal potentiation of NO production, TNF alpha was maximally
      effective when added concurrently with LPS plus IFN gamma. Nevertheless, under
      conditions that optimally potentiated NO production, both cytokines recruited
      similar numbers of astrocytes to express NOS-2 (% NOS-2-positive cells after LPS
      plus IFN gamma alone or with TNFalpha or TGF beta 1 was 9.5+/-1.2, 25.3+/-2.9,
      and 32.4+/-3.0, respectively). Interestingly, stimulation of astrocytes in the
      presence of both TGF beta 1 and TNFalpha additively increased the number of
      astrocytes that expressed NOS-2 protein (% NOS-2-positive cells was 61.0+/-4.2)
      relative to each cytokine alone. Potentiation of NO production by either TNF
      alpha or TGF beta 1 was not ablated by neutralizing antibodies to TGF beta 1 or
      TNFalpha, respectively. Thus, the two cytokines act independently to recruit
      separate pools of astrocytes to express NOS-2. These results are consistent with
      the notion that astrocytes possess an innate heterogeneity with respect to
      responsiveness to these cytokines.

PMID- 18035452
TI  - [Pericardial tamponade complicating rheumatoid arthritis: a case report].
AB  - BACKGROUND: Cardiovascular involvement in rheumatoid arthritis (RA) is
      increasingly observed and may be associated with the severity of rheumatoid
      arthritis. It is dominated by heart ischemic diseases related to atherosclerosis.
      Specific rheumatoid heart disease is commonly asymptomatic and found at autopsy
      or by echocardiography. Pericarditis is the commonest cardiac complication of RA.
      It is rarely clinically apparent and pericardial tamponade is exceptional. CASE
      REPORT: Herein, we report an unusual case of a 53-year-old female patient with a
      six-year history of seropositive and erosive rheumatoid arthritis who had
      developed a pericarditis complicated with tamponade resolved by
      pericardiocenthesis and high dose systemic steroids. Histopathology showed
      chronic inflammation and fibrosis. Under 1mg/day of colchicine, there were no
      recurrences at 10 months. CONCLUSION: Pericarditis is uncommon in rheumatoid
      arthritis. Forms with constriction or tamponade may have a fatal outcome.
      Pericardectomy usually recommended in constrictive forms, is sometimes indicated
      for tamponade. Some observations and randomised studies of idiopathic
      pericarditis suggest that colchicine may be interesting for the treatment and
      prevention of recurrences of rheumatoid arthritis-associated pericarditis.

PMID- 18035453
TI  - [Relevance of plasma exchange in the treatment of myasthenia gravis: study of 11
      cases].
AB  - BACKGROUND: The use of plasma exchange (PE) constituted an advance in the
      treatment of myasthenia. The objective of our study was to determine the
      relevance of PE in the treatment of myasthenia and to study the different
      complications which can be observed during PE. PATIENTS AND METHODS: We studied
      retrospectively 11 patients who have generalized myasthenia and underwent PE. We
      used an intermittent flow cell separator and we performed PE three times a week.
      Biological assessment was performed before and after PE for all patients. The
      exchange volume was calculated according to the patient weight, gender and the
      value of hematocrit. RESULTS: Our series included six women and five men. The
      mean age at onset of the disease was 41.4+/-14.1 years (range: 18 to 68).
      Indication of PE was myasthenia crisis (eight cases), resistance to classic
      treatment (two cases) and exacerbation after thymectomy (one case). An
      improvement was observed rapidly in five cases and delayed in three cases. The
      remaining three patients did not improve. The most frequent side effects of PE
      were hypotension (four cases), heart arrhythmia (two cases) and hypoglycemia (one
      case). Three patients dead in the seven days after the first PE. CONCLUSION: PE
      represents an interesting tool to treat severe forms of myasthenia and improve
      prognosis. High incidence of complications in our series can be explained by the
      initial disease severity, the used method of PE, the existence of associated
      illness, and a long stay in intensive care unit.

PMID- 18035454
TI  - [Inspiratory muscle myopathy and antisynthetase syndrome].
AB  - Respiratory muscle involvement is a rarely reported manifestation of inflammatory
      myopathies. We report the case of a 38-year-old woman with antisynthetase
      syndrome who presented with inflammatory myopathy and acute pulmonary
      interstitial involvement that initially improved with corticosteroids and
      immunoglobulins. A few months later dyspnoea resumed despite the absence of
      evidence of interstitial deterioration or other common diagnosis including
      vascular or infectious disorders. Isolated respiratory muscular involvement was
      evidenced by functional testing. Disease course was favourable with
      corticosteroids and immunoglobulins. Inflammatory myopathy of the antisynthetases
      syndrome could be limited or mainly expressed to respiratory muscles. Unexplained
      dyspnoea should call in mind a muscular respiratory myositis.

PMID- 18035455
TI  - Intranasal immunization with tetanus toxoid and CNF1 as a new mucosal adjuvant
      protects BALB/c mice against lethal challenge.
AB  - Although often requiring the development of efficient adjuvants, needle-free
      mucosal delivery of vaccine is of major interest as a strategy of mass
      immunization against infectious diseases. We report that mucosal immunization
      against tetanus toxoid through nasal route, together with active cytotoxic
      necrotizing factor 1 (CNF1), elicits a specific and long lasting anti-tetanus
      toxin response, comprising seric IgG and IgA, as well as mucosal IgA. Immunized
      mice were protected against a challenge with lethal doses of tetanus toxin (10 x
      LD(50)). The Rho GTPase activating toxin CNF1 is thus an attractive mucosal
      adjuvant candidate for nasal vaccines.

PMID- 18035456
TI  - A systematic review evaluating the potential for bias and the methodological
      quality of meta-analyses in vaccinology.
AB  - A systematic review was undertaken to produce an annotated bibliography of meta
      analyses in vaccinology and to evaluate their methodological quality. Based on
      our evaluation using the Oxman and Guyatt index, the methodological quality of
      the 121 meta-analyses included in this study is not satisfactory. The most
      frequent limitations include non-comprehensive bibliographic research; bias in
      the selection of the studies; lack of quality assessment of individual studies;
      absence of evaluation of heterogeneity among studies and publication bias. The
      methodological quality significantly increases with the year of publication and
      with declared financial support, without differences between profit and non
      profit support. Meta-analyses with a higher Oxman and Guyatt quality score are
      more likely to include only randomized trials and to explore appropriately
      potential sources of heterogeneity. Most of the methodological deficiencies of
      meta-analyses in vaccinology could be corrected easily, and meta-analysts should
      improve the methodological quality of their work to maintain their impact on
      policy decisions.

PMID- 18035457
TI  - Studies on the distribution of 210Po and 210Pb in the ecosystem of Point Calimere
      Coast (Palk Strait), India.
AB  - A systematic study on the natural radionuclides such as 210Po and 210Pb in the
      environmental matrices of Point Calimere ecosystem has been undertaken to
      establish a baseline data on the radiation profile of Point Calimere environment.
      The environmental samples such as water, sediment and biota (seaweeds,
      crustaceans, molluscs and fish) have been subjected to analyses. It has been
      observed that the concentration of 210Po and 210Pb in the water samples of Point
      Calimere to be 0.5 mBq/l and 1.3 mBq/l, respectively. The soft tissues of the
      organisms accumulated higher 210Po content while shells and bones contained more
      210Pb. The bivalve molluscs Meretrix casta have been identified to accumulate
      higher concentration of 210Po suggesting that they could serve as bio-indicator
      of radionuclides like 210Po in the Point Calimere ecosystem. The concentration
      factor of 210Po for the biotic components ranged from approximately 10(3) to
      10(6) while for 210Pb it ranged from approximately 10(3) to 10(5).

PMID- 18035459
TI  - Spatial trends of polybrominated diphenyl ethers in avian species: utilization of
      stored samples in the Environmental Specimen Bank of Ehime University (es-Bank).
AB  - The present study determined concentrations and patterns of polybrominated
      diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in specimens of open
      sea, and Japanese coastal and inland avian species, which have been stored in the
      Environmental Specimen Bank of Ehime University (es-Bank), to examine the spatial
      trends. PBDEs and PCBs were detected in all the muscle samples analyzed,
      suggesting that PBDE pollution has spread even to the remote open sea areas, as
      in the case of PCBs. Japanese coastal and inland birds accumulated higher
      concentrations of PBDEs than open sea birds. In addition, higher PBDE/PCB
      concentration ratios were observed in Japanese coastal and inland birds than in
      open sea birds, indicating the input of PBDEs into the Japanese terrestrial
      environment. Compositions of PBDEs varied among avian species with a predominance
      of BDE47 or BDE153. This could be due to differences in their habitat, food habit
      and/or biotransformation capacity of PBDEs.

PMID- 18035458
TI  - An exploration of step time variability on smooth and irregular surfaces in older
      persons with neuropathy.
AB  - BACKGROUND: Increased step time variability, particularly on an irregular
      surface, has been associated with impaired mobility function and a variety of
      diseases. However the biomechanical necessity, or advantage, of increasing step
      time variability has not been identified. METHODS: We performed a secondary
      analysis of gait data previously obtained on 42 subjects age 50 or older with
      neuropathy who walked on smooth and irregular surfaces, the latter with and
      without three interventions (cane, ankle orthosis and wall touch) that provided
      frontal plane support. FINDINGS: Step time variability on smooth and irregular
      surfaces was most strongly associated with reduction in step length on the
      irregular surface as compared to the smooth. More specifically, the greater the
      decrease in step length on the irregular surface the greater the step time
      variability on both surfaces and the greater the increase in step time
      variability on the irregular surface. The increase in step length on the
      irregular surface afforded by the interventions coincided with a decrease in step
      time variability. The subjects did not simultaneously demonstrate increased step
      time variability and step width range on the irregular surface. INTERPRETATION:
      Among adults age 50 and older with neuropathy, increased step time variability is
      strongly associated with the need to shorten step length on an irregular surface.
      Therefore step time variability may be a marker for instability during single
      limb stance which necessitates rapidly placed, shortened recovery steps. Such
      steps may also offer the advantage of reducing extremes in lateral foot placement
      of the swing limb, and so assist in maintaining frontal plane stability.

PMID- 18035460
TI  - Microbial transformation and degradation of polychlorinated biphenyls.
AB  - This paper reviews the potential of microorganisms to transform polychlorinated
      biphenyls (PCBs). In anaerobic environments, higher chlorinated biphenyls can
      undergo reductive dehalogenation. Meta- and para-chlorines in PCB congeners are
      more susceptible to dechlorination than ortho-chlorines. Anaerobes catalyzing PCB
      dechlorination have not been isolated in pure culture but there is strong
      evidence from enrichment cultures that some Dehalococcoides spp. and other
      microorganisms within the Chloroflexi phylum can grow by linking the oxidation of
      H(2) to the reductive dechlorination of PCBs. Lower chlorinated biphenyls can be
      co-metabolized aerobically. Some aerobes can also grow by utilizing PCB congeners
      containing only one or two chlorines as sole carbon/energy source. An example is
      the growth of Burkholderia cepacia by transformation of 4-chlorobiphenyl to
      chlorobenzoates. The latter compounds are susceptible to aerobic mineralization.
      Higher chlorinated biphenyls therefore are potentially fully biodegradable in a
      sequence of reductive dechlorination followed by aerobic mineralization of the
      lower chlorinated products.

PMID- 18035461
TI  - Using trace element concentrations in Corbicula fluminea to identify potential
      sources of contamination in an urban river.
AB  - We used the biomonitor, Corbicula fluminea, to investigate the contributions of
      trace elements associated with different point sources and land uses in a large
      river. Trace elements were analyzed in tissues of clams collected from 15
      tributary streams draining five land use or point source types: agriculture,
      forest, urban, coal-fired power plant (CFPP), and wastewater (WWTP). Clams from
      forested catchments had elevated Hg concentrations, and concentrations of arsenic
      and selenium were highest (5.0+/-0.2 and 13.6+/-0.9 microg g(-1) dry mass (DM),
      respectively) in clams from CFPP sites. Cadmium concentrations were significantly
      higher in clams from urban and CFPP sites (4.1+/-0.2 and 3.6+/-0.9 microg g(-1)
      DM, respectively). Non-metric multidimensional scaling (NMS) of tissue
      concentrations in clams clustered at CFPP and forest/agriculture sites at
      opposite ends of the ordination space, and the distribution of sites was driven
      by Cu, Zn, Cd, and Hg.

PMID- 18035462
TI  - Discourses of disease: representations of tuberculosis within New Zealand
      newspapers 2002-2004.
AB  - This paper critically examines the ways that tuberculosis (TB) has been
      represented in the print media in New Zealand over recent years (2002-2004). Our
      broad contention is that, notwithstanding its biomedical reality, TB is socially
      constructed by, and through, human experience. Further, public health
      practitioners depend, to a large extent, on the media to alert the public to
      threats of disease and opportunities for protection. However, the messages
      conveyed are sometimes neither helpful nor accurate. In our analysis of TB
      coverage in three major daily newspapers in New Zealand, we enumerate and
      classify references to the disease, as well as undertake a discursive analysis of
      the revealed themes. Of the 366 texts we retrieved in the database search, we
      selected 120 for in-depth analysis. Our examination indicated the importance of
      bovine TB within the national consciousness, the stigmatised character of TB and
      the association between TB and immigrants. We observe that newspaper 'stories' in
      general, and commentaries by public health officials in particular, are
      invariably offered on a 'case by case' basis. We conclude that this specificity
      in time and place avoids more challenging discourses linking TB with deeply
      embedded determinants of health such as the strong link between TB and poverty.

PMID- 18035463
TI  - A toxicologic and dermatologic assessment of related esters and alcohols of
      cinnamic acid and cinnamyl alcohol when used as fragrance ingredients.
AB  - An evaluation and review of a structurally related group of fragrance materials.

PMID- 18035464
TI  - Fragrance material review on isoamyl cinnamate.
AB  - A toxicologic and dermatologic review of isoamyl cinnamate when used as a
      fragrance ingredient is presented.

PMID- 18035465
TI  - Fragrance material review on cinnamyl isobutyrate.
AB  - A toxicologic and dermatologic review of cinnamyl isobutyrate when used as a
      fragrance ingredient is presented.

PMID- 18035466
TI  - Effects of chitosan oligosaccharide (COS) on the glycerol-induced acute renal
      failure in vitro and in vivo.
AB  - The purpose of this study was to investigate the effects of
      chitosanoligosaccharide (COS) on the change of inflammatory response, renal
      function factor, and renal oxidative stress in glycerol-induced ARF in vitro and
      in vivo. The molecular weight of COS was approximately below 10 kDa with 90%
      degree of deacetylation. Renal proximal tubular cells were treated with only COS
      (0, 0.01, 0.025, 0.05, 0.075 and 0.1%) or COS in the presence of glycerol (4mM).
      And rats were administered with glycerol (50%, 8 ml/kg) by intramuscular
      injection for the induction of ARF. For identification the protection effect of
      COS in the glycerol-induced ARF, rats were administered by COS (0.05 and 0.1%)
      using P.O. injection. The enzymatic activity of the released RDPase was assayed
      by the fluorometric method. The level of TNF-alpha in kidney or the culture
      medium was quantified using ELISA kit (R&D Systems, Minneapolis, USA) and,
      nitrite concentration was determined by the Griess reaction. We showed that COS
      stimulated the production of TNF-alpha, NO and the released RDPase. Glycerol
      increased the concentration of RDPase in kidney and decreased the released RDPase
      in proximal tubular cells. And, glycerol increased the production of NO, TNF
      alpha, creatinine, and MDA, and decreased SOD. However, COS recovered the
      glycerol-induced inflammatory response, renal function factor, and antioxidant
      effect in kidney. COS had the antioxidant activity and the anti-inflammatory
      effect. And maybe that characteristics could help recover the glycerol-induced
      ARF.

PMID- 18035467
TI  - Fragrance material review on cis-3-hexenyl cinnamate.
AB  - A toxicologic and dermatologic review of cis-3-hexenyl cinnamate when used as a
      fragrance ingredient is presented.

PMID- 18035468
TI  - Fragrance material review on cinnamyl tiglate.
AB  - A toxicologic and dermatologic review of cinnamyl tiglate when used as a
      fragrance ingredient is presented.

PMID- 18035469
TI  - Fragrance material review on cinnamyl benzoate.
AB  - A toxicologic and dermatologic review of cinnamyl benzoate when used as a
      fragrance ingredient is presented.

PMID- 18035470
TI  - Fragrance material review on benzyl salicylate.
AB  - A toxicologic and dermatologic review of benzyl salicylate when used as a
      fragrance ingredient is presented.

PMID- 18035471
TI  - Fragrance material review on cis-3-hexenyl salicylate.
AB  - A toxicologic and dermatologic review of cis-3-hexenyl salicylate when used as a
      fragrance ingredient is presented.

PMID- 18035472
TI  - Fragrance material review on butyl salicylate.
AB  - A toxicologic and dermatologic review of butyl salicylate when used as a
      fragrance ingredient is presented.

PMID- 18035473
TI  - Liver and colon DNA oxidative damage and gene expression profiles of rats fed
      Arabidopsis thaliana mutant seeds containing contrasted flavonoids.
AB  - Plant polyphenols, such as flavonoids, comprise many compounds, ranging from
      simple phenolic molecules (i.e. flavonols, anthocyanins) to polymeric structures
      with high molecular weight (as proanthocyanidins, PAs). We investigated the
      effects of flavonoids by feeding Wistar rats Arabidopsis thaliana seeds carrying
      mutations in key enzymes of the flavonoid biosynthetic pathway (15% w/w seeds for
      4 weeks). The seeds used were: Ws-2 wild-type containing flavonols and PAs, tt3-4
      mutant containing flavonols only, ban-5 accumulating flavonols and anthocyanins,
      tt4-8 mutant, deprived of flavonoids. DNA oxidative damage was significantly
      reduced only in the liver of rats fed tt3-4 mutant seeds. Microarray analysis of
      the liver revealed down-regulation of genes associated with oxidative stress,
      Krebs cycle, electron transport and proteasome degradation in all experimental
      groups compared to the tt4-8-fed reference rats; therefore, these effects were
      due to the flavonol content and not to high molecular weight compounds. We
      observed a down-regulation of inflammatory response genes in the colon mucosa in
      ban-5- fed rats, probably due to anthocyanin content. In conclusion, flavonols
      exhibited antioxidant effects at systemic level, whereas high molecular weight
      flavonoids affected only the colon, probably due to their limited absorption.

PMID- 18035474
TI  - [Reduction mammoplasty and mastopexy with limited inversed T scar].
AB  - Our retrospective study done on 184 cases of hypertrophic mammary gland and
      ptosis on little, medium, and high grade confirms that we have approached an
      original technique, giving an inversed T scar, reducing the horizontal part of
      our scar instead of the original Pitanguy scar.

PMID- 18035475
TI  - Arterial blood gases during basic life support of human cardiac arrest victims.
AB  - BACKGROUND: Ventilation with tidal volumes sufficient to raise the victim's chest
      is an integral part of guidelines for lay-rescuer basic life support, but optimal
      tidal volume, frequency and ratio to chest compressions are not known. METHODS:
      Adults with non-traumatic, out-of-hospital cardiac arrest, who were not
      successfully resuscitated following advanced life support by the staff of a
      physician-manned ambulance, were included. Advanced life support comprised
      tracheal intubation and mechanical ventilation with tidal volume of 700 ml and
      100% oxygen, 12 times per min. An arterial blood sample was drawn at the end of
      the resuscitation attempt and analysed on the scene. After the victim was
      declared dead, basic life support was initiated with chest compressions and mouth
      to-mask or mouth-to-tracheal tube ventilation (15:2), with volumes sufficient to
      make the chest rise. The tracheal tube was equipped with an impedance valve to
      avoid passive ventilation secondary to chest compressions. Arterial blood samples
      were drawn after 7-8 min of basic life support and analysed on the scene.
      RESULTS: Six men and two women, median (range) age 72 (32-86) years, were
      included in the study. Four of these received mouth-to-mask ventilation and four
      mouth-to-tracheal tube ventilation. Mean (S.D.) arterial blood carbon dioxide and
      oxygen tension during advanced life support were 6.4 (1.4)kPa and 22 (15)kPa,
      respectively. Similar values during basic life support were 9.6 (1.9)kPa and 8.5
      (1.6)kPa, respectively, with no differences between the ventilation methods.
      CONCLUSION: Ventilation during basic life support performed according to
      international guidelines (2000) resulted in arterial hypercapnia and hypoxia.

PMID- 18035476
TI  - Association of smoking during pregnancy and fetal growth restriction: subgroups
      of higher susceptibility.
AB  - OBJECTIVE: To analyze the association between maternal smoking and fetal growth
      restriction, defined as a failure to achieve the growth potential, and to define
      subgroups of higher susceptibility for this association. STUDY DESIGN: A
      definition of growth restriction by customized birthweight standards applied to
      13,661 non-malformed singleton deliveries. Customization was performed by
      maternal ethnic origin, height, booking weight, parity, gestational age at
      delivery and fetal gender. The adjusted risk of smoking for customized smallness
      for-gestational age and the identification of subgroups with higher
      susceptibility were assessed by logistic regression. RESULTS: Overall, the
      adjusted odds ratio of smoking (all levels of exposure grouped) for the
      occurrence of growth restriction was 1.9 (95% confidence interval: 1.69-2.13).
      Smoking was etiologically responsible for 13.9% (95% confidence interval: 11.2
      16.5) of the cases of growth restriction occurring in the population. Smoking
      resulted in an increasingly greater risk of growth restriction with progressive
      levels of cigarette consumption. The risk of smoking for fetal growth restriction
      was significantly greater in older women and those with a previous history of
      spontaneous preterm delivery. CONCLUSIONS: Smoking is associated with a higher
      risk for growth restriction. In addition, older pregnant women and those with a
      previous history of preterm delivery have an increased susceptibility.

PMID- 18035477
TI  - Forkhead transcription factor FOXO subfamily is essential for reactive oxygen
      species-induced apoptosis.
AB  - Intracellular accumulation of reactive oxygen species is implicated in the
      pathogenesis of cancer and other diseases by disturbing proper cell cycle control
      or cell survival. Here, we show that the expression and phosphorylation of FOXO
      is drastically affected by H(2)O(2) treatment, resulting in drastic induction of
      luteal cell apoptosis. Western blot analysis revealed that FOXO1a accumulated
      preferentially in the nucleus upon ROS stimuli, resulting in the transactivation
      of IRS promoter activity driven by H(2)O(2)-activated FOXO1a. Because ROS-induced
      cell death was suppressed by co-transfection of a FOXO3a mutant that lacks the
      activation-domain of transcription, transactivation of pro-apoptotic genes by
      FOXO was necessary to cause ROS-induced apoptosis. In fact, expression of several
      pro-apoptotic genes, such as Bim and BCL-6 was induced in H(2)O(2)-stimulated
      cells, and was blocked by co-transfection of dominant-negative type FOXO3a
      mutant. These findings indicate that FOXO is a key regulator of ROS-induced
      apoptosis in mammalian cells.

PMID- 18035478
TI  - Gene expression profiling during Forskolin induced differentiation of BeWo cells
      by differential display RT-PCR.
AB  - The differentiation of cytotrophoblasts into syncytiotrophoblasts in the placenta
      has been employed as a model to investigate stage specific expression as well as
      regulation of genes during this process. While the cytotrophoblasts are highly
      invasive and proliferative with relatively less capacity to synthesize pregnancy
      related proteins, the multinucleated syncytiotrophoblasts are non-proliferative
      and non-invasive. However, syncytiotrophoblasts are the site of synthesis of a
      variety of protein, peptide and steroid hormones as well as several growth
      factors. Both the freshly isolated cytotrophoblasts from human placenta as well
      as the BeWo cell, a choriocarcinoma cell line model which retain several
      characteristic of cytotrophoblasts has been employed by us to study regulation of
      differentiation. In the present study, we have employed the differential display
      RT-PCR analysis (DD-RT-PCR) to evaluate gene expression changes during Forskolin
      induced in vitro differentiation of BeWo cells. We have identified several genes
      which are differentially expressed during differentiation and the differential
      expression of 10 transcripts was confirmed by Northern blot analysis. Based on
      the identity of the transcripts an attempt has been made to relate the known
      function of the gene products, to changes observed during differentiation. Of the
      several transcripts, one of the transcripts, namely Secretory Leukocyte Protease
      Inhibitor (SLPI) which is known to have multiple functions was found to increase
      15-fold in the syntiotrophoblast.

PMID- 18035479
TI  - Pediatric moyamoya disease presenting with intracerebral hemorrhage--report of
      three cases and review of the literature.
AB  - Intracerebral hemorrhage in patients with moyamoya disease is rare in children.
      We report three unique cases of pediatric moyamoya disease with hemorrhagic
      onset. Two 7-year-old girls and a 9-year-old girl were admitted to our hospital
      because of intracerebral hemorrhage associated with angiographically verified
      moyamoya disease. Two of them did not demonstrate either an ischemic episode or
      cerebral infarct on the magnetic resonance images. A decreased regional cerebral
      blood flow was revealed on single photon emission computed tomography in two
      patients, who developed cerebral infarction in the acute stage following
      hemorrhage. They underwent superficial temporal artery-middle cerebral artery
      anastomoses combined with encephalo-myo-synangiosis, and have not experienced any
      further ischemic episodes thereafter. Hemodynamic insufficiency associated with
      moyamoya disease could cause intracerebral hemorrhage even in children. Adequate
      management in the acute stage of hemorrhage and revascularization surgery are
      recommended to prevent cerebral infarction, which may easily occur in pediatric
      patients with moyamoya disease.

PMID- 18035480
TI  - Sellar abnormalities in female first-degree relatives.
AB  - Non-pituitary lesions account for a minority of sellar region abnormalities. We
      report the unusual occurrence of non-pituitary sellar/suprasellar lesions in a
      mother and her two daughters. Each of these cases was diagnosed and managed
      differently, illustrating the relative importance of radiographic imaging, tumor
      markers and histopathologic examination in the diagnosis and treatment of
      intracranial disease. The mother had histologically confirmed Rathke's cleft cyst
      (RCC) with typical radiographic and histologic appearance. One daughter was
      treated presumptively for germinoma based on characteristic radiographic studies
      and slightly elevated tumor marker. The other daughter's lesion exhibited
      radiographic characteristics concerning for pituitary macroadenoma but with
      slightly elevated germ cell tumor marker, raising the suspicion for germinoma.
      Biopsy of the intrasellar mass revealed only proteinaceous material and normal
      anterior pituitary, consistent with cyst content without evidence of neoplasm.
      Without a clear unifying diagnosis it is difficult to posit an underlying
      pathology or genetic mechanisms in this unusual set of cases. At least two of the
      patients had benign cysts. The diagnosis of the third patient is unclear as there
      was no tissue biopsy. However, it is highly improbable that three female first
      degree relatives would develop such lesions in the same brain region simply by
      chance.

PMID- 18035481
TI  - PTHrP promotes homotypic aggregation of breast cancer cells in three-dimensional
      cultures.
AB  - Parathyroid hormone-related protein (PTHrP) regulates growth and migration of
      adherent breast cancer cells. Here, we show that PTHrP also interferes with the
      ability of breast cancer cells to aggregate in suspension cultures. Cell colonies
      were significantly smaller when the expression of PTHrP or its target genes,
      integrin alpha6 or KISS-1, was suppressed by RNA interference. TGFbeta1, a
      stimulator of PTHrP transcription, abolished the effect of PTHrP and KISS-1
      specific siRNAs and increased ERK1/2 phosphorylation, whereas inhibition of
      ERK1/2 phosphorylation by U0126 reduced colony size. PTHrP and KISS-1 may
      regulate colony formation in 3D by influencing ERK1/2 phosphorylation.

PMID- 18035483
TI  - Adsorption of basic dye on high-surface-area activated carbon prepared from
      coconut husk: equilibrium, kinetic and thermodynamic studies.
AB  - Adsorption isotherm and kinetics of methylene blue on activated carbon prepared
      from coconut husk were determined from batch tests. The effects of contact time
      (1-30 h), initial dye concentration (50-500 mg/l) and solution temperature (30-50
      degrees C) were investigated. Equilibrium data were fitted to Langmuir,
      Freundlich, Temkin and Dubinin-Radushkevich isotherm models. The equilibrium data
      were best represented by Langmuir isotherm model, showing maximum monolayer
      adsorption capacity of 434.78 mg/g. The kinetic data were fitted to pseudo-first
      order, pseudo-second-order and intraparticle diffusion models, and was found to
      follow closely the pseudo-second-order kinetic model. Thermodynamic parameters
      such as standard enthalpy (DeltaH degrees), standard entropy (DeltaS degrees) and
      standard free energy (DeltaG degrees) were evaluated. The adsorption interaction
      was found to be exothermic in nature. Coconut husk-based activated carbon was
      shown to be a promising adsorbent for removal of methylene blue from aqueous
      solutions.

PMID- 18035482
TI  - Regulation of XAF1 expression in human colon cancer cell by interferon beta:
      activation by the transcription regulator STAT1.
AB  - XIAP-associated factor 1 (XAF1) is a novel tumor suppressor and interferon
      stimulated gene (ISG). Interferon beta (IFNbeta) exerts anti-proliferative effect
      and induces apoptosis through the Jak-Stat signaling cascade by the type I
      Interferon receptor (IFN-R), which initiates gene transcription of those
      biological effectors of IFNbeta. The aim of this study is to determine the effect
      of IFNbeta on XAF1 expression and the putative mechanisms mediated by the
      critical role of signal transducers and activators of transcription 1 (Stat1).
      Gene expression was detected by RT-PCR and Western blot analysis. The promoter
      activity of XAF1 was examined by luciferase reporter assay. The activity of
      interferon stimulated response element (ISRE) was assessed by electrophoretic
      mobility shift assay (EMSA) and quantitative chromatin immunoprecipitation assay
      (Q-ChIP). Results showed that IFNbeta stimulated XAF1 promoter activity in colon
      cancer cell line DLD1 in a time- and dose-dependent manner. A high affinity ISRE
      binding element (ISRE-XAF1) was located in -55 to -66 nt upstream of the first
      ATG site of XAF1 gene. Deletion of ISRE-XAF1 completely abrogated basal and
      IFNbeta-induced promoter activity. IFNbeta-induced XAF1 expression was mediated
      by Stat1 through the interaction with ISRE-XAF1. Knocking down of the Stat1
      expression and blocking its phosphorylation decreased IFNbeta-induced XAF1
      expression. Results suggested that induction of an immediate early response gene
      XAF1 by IFNbeta was mediated by the transcription regulator Stat1 through the
      ISRE site within the promoter region of XAF1 gene in colon cancer.

PMID- 18035484
TI  - Influence of physicochemical treatments on iron-based spent catalyst for
      catalytic oxidation of toluene.
AB  - The catalytic oxidation of toluene was studied over an iron-based spent and
      regenerated catalysts. Air, hydrogen, or four different acid solutions (oxalic
      acid (C2H2O4), citric acid (C6H8O7), acetic acid (CH3COOH), and nitric acid
      (HNO3)) were employed to regenerate the spent catalyst. The properties of
      pretreated spent catalyst were characterized by the Brunauer Emmett Teller (BET),
      inductively coupled plasma (ICP), temperature programmed reduction (TPR), and X
      ray diffraction (XRD) analyses. The air pretreatment significantly enhanced the
      catalytic activity of the spent catalyst in the pretreatment temperature range of
      200-400 degrees C, but its catalytic activity diminished at the pretreatment
      temperature of 600 degrees C. The catalytic activity sequence with respect to the
      air pretreatment temperatures was 400 degrees C>200 degrees C>parent>600 degrees
      C. The TPR results indicated that the catalytic activity was correlated with both
      the oxygen mobility and the amount of available oxygen on the catalyst. In
      contrast, the hydrogen pretreatment had a negative effect on the catalytic
      activity, and toluene conversion decreased with increasing pretreatment
      temperatures (200-600 degrees C). The XRD and TPR results confirmed the formation
      of metallic iron which had a negative effect on the catalytic activity with
      increasing pretreatment temperature. The acid pretreatment improved the catalytic
      activity of the spent catalyst. The catalytic activity sequence with respect to
      different acids pretreatment was found to be oxalic acid>citric acid>acetic
      acid>or=nitric acid>parent. The TPR results of acid pretreated samples showed an
      increased amount of available oxygen which gave a positive effect on the
      catalytic activity. Accordingly, air or acid pretreatments were more promising
      methods of regenerating the iron-based spent catalyst. In particular, the oxalic
      acid pretreatment was found to be most effective in the formation of FeC2O4
      species which contributed highly to the catalytic combustion of toluene.

PMID- 18035485
TI  - Fractionation of the organic matter contained in leachate resulting from two
      modes of landfilling: an indicator of waste degradation.
AB  - Three experimental pilots were set up at the semi-industrial scale to assess the
      impact of leachate recirculation and Mechanical Biological Pre-treatment (MBP)
      before landfilling on the biological degradation of landfilled wastes. The
      organic matter contained in leachates resulting from these pilots has been used
      as an indicator of waste degradation. Fractionations were carried out (i) using
      XAD resins in order to divide the organic matter into several fractions according
      to the hydrophobic character of the molecules and (ii) using an ultrafiltration
      protocol to divide the organic matter into several fractions according to the
      apparent molecular weight of molecules. Three phases of degradation are
      determined according to the distribution of the organic matter and according to
      the humification rate. The humification process seems to be more rapid for MBP
      leachates than for Bioreactor leachate. These results were confirmed by the
      ultrafiltration results indicating that, to date, MBP leachates contain more
      molecules with a high molecular weight than Bioreactor leachate. However, this
      could be explained by an interruption of waste degradation due to an accumulation
      of volatile fatty acids.

PMID- 18035486
TI  - In vitro release dynamics of thiram fungicide from starch and poly(methacrylic
      acid)-based hydrogels.
AB  - In order to make the judicious use of pesticide/fungicide and to maintain the
      environment and ecosystem we have developed the starch and poly(methacrylic acid)
      based agrochemical delivery system for their controlled and sustained release.
      The delivery device was prepared by using N,N'-methylenebisacrylamide (N,N'
      MBAAm) as crosslinker and was characterized with FTIR, TGA and with swelling
      studies as a function of time and crosslinker concentration. This article
      discusses the swelling kinetics of polymer matrix and release dynamics of thiram
      (fungicide) from hydrogels for the evaluation of the diffusion mechanism and
      diffusion coefficients. The values of the diffusion exponent 'n' for both cases,
      that is the swelling of hydrogels and for the release of thiram from the
      hydrogels have been observed between 0.7 and 0.9 when the concentration of the
      crosslinker in the polymers were varied from 6.49x10(-3) to 32.43x10(-3) moles/L.
      It is inferred from the values of the 'n' that Non-Fickian diffusion mechanism
      has occurred in both the cases.

PMID- 18035487
TI  - A review of the criteria for people exposure to radiant heat flux from fires.
AB  - The NFPA 59A Standard and the Federal Regulation, 49 CFR Part 193, stipulate a
      level of 5 kW/m(2) as the criterion for determining the hazard distance to people
      exposure from a LNG fire. Another regulation (24CFR, Section 51.204) while
      stipulating a lower exposure limit of 1.42 kW/m(2) provides administrative relief
      from the regulation if mitigation measures are provided. Several countries in
      Europe and the Far East have adopted both a specified heat flux value (generally,
      5 kW/m(2)) as well as modified dose criteria for human exposure hazard
      calculation in risk assessments. In some cases, the regulations in Europe require
      the use of lower values for children and physically challenged persons. This
      paper reviews the available literature on the phenomenon of skin burn caused by
      radiant heat exposure. The associated thermal and spectral properties of human
      skin are reviewed. The basis for regulatory setting, of 5 kW/m(2) and other
      exposure criteria (as a part of hazard and risk calculations) for evaluating
      distances to hazards from the exposure of people to radiant heat effects of large
      fires, is evaluated. An example calculation is provided to show the extent of
      reduction in the hazard distance to specified radiant heat flux from a fire when
      the spectral reflection and absorption properties of skin are considered with and
      without the inclusion of the mitigating effects of clothing. The results indicate
      that hazard distances calculated including the reflective and band absorptive
      properties (in IR wavelength) of skin results in a reduction of between 30 and
      50% in the hazard distances obtained with current methodology, which ignores
      these effects. Unfortunately, there are no test results, from full-scale human
      exposure-to-IR radiation, with which these predictions can be compared.

PMID- 18035488
TI  - Degradation mechanism and kinetic model for photocatalytic oxidation of PVC-ZnO
      composite film in presence of a sensitizing dye and UV radiation.
AB  - White or plastic pollution has become a serious concern to the environmentalists
      for the last few years. Degradation of waste plastics in conventional
      incinerators leads to emission of carcinogenic dioxins to the atmosphere. In this
      work, an attempt has been made for the photocatalytic degradation of polyvinyl
      chloride (PVC) using ZnO as semi-conductor catalyst in the form of PVC-ZnO
      composite film. The surface morphology as well as the FTIR spectroscopy of the
      irradiated film has been critically examined. The degradation was measured by
      weight loss data and was found to follow a pseudo-first order rate equation. The
      various parameters studied were loading of the semi-conductor, intensity of UV
      radiation and presence of Eosin Y as a sensitizing dye. It was observed that dye
      sensitization enhanced degradation of PVC to a large extent. A possible mechanism
      has been suggested and the corresponding rate equation has been modeled for the
      dye-sensitized rate of degradation. The model has been validated by the
      experimental data.

PMID- 18035489
TI  - Mass and count nouns activate different brain regions: an ERP study on early
      components.
AB  - In the present study, event related brain potentials (ERPs) showed that, in an
      implicit Lexical decision task in which participants had to decide whether a word
      or a pseudoword was presented, a very early distinction between Mass and Count
      nouns was found at 160 ms after word onset (N150). Mass nouns elicited greater
      left-lateralization over frontal locations while Count nouns were more
      lateralized in the left occipito-parietal sites. In the 430-490 ms interval
      activity and lateralization shifted to anterior sites and a different
      distribution was found between Mass nouns, Count nouns and Pseudowords. Mass
      nouns showed greater left-lateralization both in anterior and posterior regions,
      whereas Count nouns showed relatively less left-lateralization especially over
      frontal cortex. Results point to a functional distinction between Mass and Count
      nouns as indicated by the very early automatic N150 difference between the two
      categories. Count nouns involved left visual associative regions that are
      typically relevant for object recognition and categorization. Mass nouns,
      instead, required the activation of more widely spread out linguistic networks
      that included also left frontal sites, a result that indicates a more difficult
      and engaging automatic retrieval and an extended cortical representation of these
      nouns.

PMID- 18035490
TI  - Neuroglobin protects against nitric oxide toxicity.
AB  - Neuroglobin (Ngb) is a novel vertebrate globin expressed principally in neurons.
      Ngb expression is induced by hypoxia and ischemia, and Ngb protects neurons
      against these insults. The mechanism of Ngb's protective action is unknown, but
      its ability to bind NO suggests that NO scavenging might be involved. To test
      this hypothesis, we treated wild type and Ngb-transfected HN33 (mouse hippocampal
      neuronxN18TG2 neuroblastoma) cells with NO donors and compared their sensitivity
      to NO-induced cell death. Ngb overexpression shifted concentration-toxicity
      curves to the right, indicating reduced susceptibility to NO or is metabolites.
      The results suggest that the ability of Ngb to neutralize the neurotoxic effects
      of reactive nitrogen species may be an important contributor to its
      neuroprotective properties.

PMID- 18035491
TI  - Peptidoglycan recognition protein-S (PGRP-S) is upregulated by NF-kappaB.
AB  - Cerebral ischemia triggers inflammation and apoptosis, and the transcription
      factor NF-kappaB is a key regulator of both events. Here, we report on the
      induction of the peptidoglycan recognition protein-S (PGRP-S) in a mouse model of
      cerebral ischemia. Upregulation was reduced if the NF-kappaB subunit RelA was
      conditionally deleted in the brain. Regulation of PGRP-S transcription by RelA
      was confirmed in vitro. Cotransfection of a RelA expression plasmid stimulated
      the expression of a PGRP-S luciferase fusion gene. Mutation of two NF-kappaB
      response elements in the PGRP-S promoter disrupted stimulation by RelA. To
      investigate the function of PGRP-S in cerebral ischemia, we subjected PGRP-S(-/-)
      mice to cerebral ischemia. However, there was no difference in the infarct size
      in PGRP-S-deficient mice compared to controls. In summary, the data show that
      PGRP-S is induced in cerebral ischemia by RelA, but its role in ischemia is
      unclear.

PMID- 18035492
TI  - The ventrolateral periaqueductal gray is involved in the cardiovascular response
      evoked by l-glutamate microinjection into the lateral hypothalamus of
      anesthetized rats.
AB  - Microinjection of l-glutamate (l-glu: 1, 3, 10 and 30nmol/100nL) into the lateral
      hypothalamus (LH) caused dose-related depressor and bradycardiac responses. The
      cardiovascular response to l-glu stimulation of the LH was blocked by
      pretreatment of the ventrolateral portion of the periaqueductal gray matter
      (vlPAG) with CoCl2 (1mM/100nL), indicating the existence of a synaptic relay of
      the hypotensive pathway in that area. Furthermore, the response to l-glu was
      blocked by pretreatment of the vlPAG with 2nmol/100nL of the selective NMDA
      receptor antagonist LY235959 and was not affected by pretreatment with
      2nmol/100nL of the selective non-NMDA-receptor antagonist NBQX, suggesting a
      mediation of the hypotensive response by NMDA receptors in the vlPAG. In
      conclusion, our results indicate that the hypotensive pathway activated by
      microinjection of l-glu into the LH involves a NMDA synaptic relay in the vlPAG.

PMID- 18035494
TI  - Pain-related evoked potentials are modulated across the cardiac cycle.
AB  - Evidence suggests that the arterial baroreceptors modulate pain. To examine
      whether cortical processing of nociception is modulated by natural variations in
      arterial baroreceptor stimulation during the cardiac cycle, peak-to-peak
      amplitudes of the N2-P2 pain-related potential and pain ratings were recorded in
      response to noxious laser stimulation at different times during the cardiac cycle
      in 10 healthy males. Significant variations in the N2-P2 amplitudes occurred
      across the cardiac cycle, with smaller amplitudes midcycle, indicating that
      cortical processing of nociception was attenuated during systole compared to
      diastole. Pain ratings did not vary across the cardiac cycle. These data support
      the hypothesis that arterial baroreceptors modulate the processing of nociception
      during each cardiac cycle.

PMID- 18035493
TI  - TNF signaling contributes to the development of nociceptive sensitization in a
      tibia fracture model of complex regional pain syndrome type I.
AB  - Tibia fracture in rats initiates a cascade of nociceptive, vascular, and bone
      changes resembling complex regional pain syndrome type I (CRPS I). Previous
      studies suggest that the pathogenesis of these changes is attributable to an
      exaggerated regional inflammatory response to injury. We postulated that the pro
      inflammatory cytokine tumor necrosis factor alpha (TNF) might mediate the
      development of CRPS-like changes after fracture. RT-PCR and EIA assays were used
      to evaluate changes in TNF expression and content in skin, nerve, and bone after
      fracture. Bilateral hindpaw thickness, temperature, and nociceptive thresholds
      were determined, and bone microarchitecture was measured using microcomputed
      tomography. Lumbar spinal cord Fos immunostaining was performed for
      quantification of Fos positive neurons. After baseline testing, the distal tibia
      was fractured and the hindlimb casted for 4 weeks. The rats were subcutaneously
      injected either with a soluble TNF receptor type 1 (sTNF-R1, 5mg/kg/d) or saline
      every 3 days over 28 days and then were retested at 4 weeks post-fracture. Tibia
      fracture chronically upregulated TNF expression and protein levels in the hindpaw
      skin and sciatic nerve. After fracture the rats developed hindpaw mechanical
      allodynia and unweighting, which were reversed by sTNF-R1 treatment. Consistent
      with the behavioral data, spinal Fos increased after fracture and this effect was
      inhibited by sTNF-R1 treatment. Collectively, these data suggest that facilitated
      TNF signaling in the hindlimb is an important mediator of chronic regional
      nociceptive sensitization after fracture, but does not contribute to the hindlimb
      warmth, edema, and bone loss observed in this CRPS I model.

PMID- 18035495
TI  - Validity of 24-h recall ratings of pain severity: biasing effects of "Peak" and
      "End" pain.
AB  - Despite the frequent use of pain recall ratings in clinical research, there
      remains doubt about the ability of individuals to accurately recall their pain.
      In particular, previous research indicates the possibility that the most pain
      experienced during a recall period and the most recent pain experienced (known as
      peak and end effects, respectively) might bias recall ratings. The current study
      used data from a published clinical trial to determine the relative validity of a
      24-h recall rating of average post-operative pain and the nature and extent of
      any biasing influence of peak and end effects on nine separate 24-h recall
      ratings. The results supported a statistically significant but small biasing
      influence of both peak and end pain. Also, the influence of peak pain was
      stronger than that of end pain. However, the biasing impact of both peak and end
      pain together was very small, suggesting that 24-h recall ratings are adequately
      valid indicants of average pain for patients participating in post-surgery
      clinical pain trials.

PMID- 18035496
TI  - Reassurance: help or hinder in the treatment of pain.

PMID- 18035497
TI  - The Bath Adolescent Pain--Parental Impact Questionnaire (BAP-PIQ): development
      and preliminary psychometric evaluation of an instrument to assess the impact of
      parenting an adolescent with chronic pain.
AB  - When an adolescent has chronic pain many aspects of a parent's life can be
      affected, including their emotional and social functioning. The assessment of
      this multidimensional parental impact is an essential, yet often neglected,
      clinical task. This study reports on the development and psychometric evaluation
      of the Bath Adolescent Pain--Parental Impact Questionnaire (BAP-PIQ), an
      assessment tool comprising multiple scales thought to be relevant for better
      understanding changes in functioning and behavior associated with parenting an
      adolescent with chronic pain. A sample of 194 parents of adolescents with chronic
      pain, recruited from three UK clinics, completed the 94 item draft inventory.
      Frequency and item correlation analyses resulted in a final inventory of 62
      items. Internal consistency of all eight scales was established based on
      Cronbach's alpha. Convergent validity was undertaken by comparison of individual
      scales with existing validated measures of parental stress, mood, parenting
      behavior, marital adjustment, and general functioning. The temporal reliability
      of each scale was established using a sub-sample of 46 participants over a 14-day
      period. Psychometric evaluation suggests that the inventory yields a reliable and
      valid assessment of the multiple impacts of parenting an adolescent with chronic
      pain. The BAP-PIQ may offer a comprehensive assessment of these impacts in both a
      research and a clinical setting. Further study of the validity of BAP-PIQ scales
      and their ability to detect clinically meaningful change would be of use.
      Additional data from samples comprising fathers of adolescents with chronic pain
      and parents of adolescents with non-musculoskeletal pain would be of benefit.

PMID- 18035498
TI  - Children's self-reported pain at the dentist.
AB  - The aim of the present study is to get an insight into the pain report of
      children over two sequential dental visits. Furthermore, it was studied whether
      age, previous dental experience, level of dental anxiety and injection site were
      of influence on the self-reported pain of children during the first and second
      treatment session. One hundred and forty-seven children (4-11 years old) were
      included in the study. After receiving a local anesthesia injection prior to
      their dental treatment, they were asked how much pain they had felt. The level of
      dental anxiety was measured once by the parental version of the Dental Subscale
      of the Children's Fear Survey Schedule. Young children with a low level of dental
      anxiety show a sensitized reaction trend for self-reported pain over two
      sequential dental visits. Young children with a high level of dental anxiety
      reported the most pain on the first treatment session. For the older children,
      the children having previous dental experience gave the highest pain ratings on
      the first treatment session. Furthermore, for both young and older children the
      amount of pain reported for the second injection was best predicted by the amount
      of pain reported for the first injection, whereby higher scores the first time
      predict higher scores the second time. In conclusion, the memory of previous
      experience with dentistry and earlier treatment sessions seems of great influence
      on the behaviour and the experience of children during subsequent treatment
      sessions.

PMID- 18035499
TI  - Prospects for analyzing the electronic properties in nanoscale systems by VEELS.
AB  - Valence electron energy-loss spectroscopy in the scanning transmission electron
      microscope can provide detailed information on the electronic structure of
      individual nanostructures. By employing the latest advances in electron optical
      devices, such as a probe aberration corrector and an electron monochromator, the
      probe size, spectroscopic resolution, probe current and primary electron energy
      can be varied over a large range. This flexibility is particularly important for
      nanostructures where each of these variables needs to be carefully
      counterbalanced in order to collect spectroscopic data without altering the
      integrity of the sample. Here the implementation of valence electron energy-loss
      spectroscopy to the study of nanostructures is discussed, with particular mention
      to the theoretical understanding of each of the contributions to the overall
      spectrum.

PMID- 18035500
TI  - Quantitative characterization of crosstalk effects for friction force microscopy
      with scan-by-probe SPMs.
AB  - If the photodetector and cantilever of an atomic force microscope (AFM) are not
      properly adjusted, crosstalk effects will appear. These effects disturb
      measurements of the absolute vertical and horizontal cantilever deflections,
      which are involved in friction force microscopy (FFM). A straightforward
      procedure is proposed to study quantitatively crosstalk effects observed in scan
      by-probe SPMs. The advantage of this simple, fast, and accurate procedure is that
      no hardware change or upgrade is needed. The results indicate that crosstalk
      effects depend not only on the alignment of the detector but also on the
      cantilever properties, position, and detection conditions. The measurements may
      provide information on the origin of the crosstalk effect. After determination of
      its magnitude, simple correction formulas can be applied to correct the crosstalk
      effects and then the single-load wedge method, using a commercially available
      grating, can be employed for accurate calibration of the lateral force.

PMID- 18035501
TI  - Selective induction of metabotropic glutamate receptor 1- and metabotropic
      glutamate receptor 5-dependent chemical long-term potentiation at oriens/alveus
      interneuron synapses of mouse hippocampus.
AB  - Synaptic plasticity in inhibitory interneurons is essential to maintain a proper
      equilibrium between excitation and inhibition in hippocampal network. Recent
      studies showed that theta-burst-induced long-term potentiation (LTP) at
      excitatory synapses of oriens/alveus (O/A) interneurons in CA1 hippocampal region
      required the activation of metabotropic glutamate receptor (mGluR) 1. However
      these interneurons also express mGluR5 and the contribution of this receptor
      subtype in interneuron synaptic plasticity remains unexplored. We combined
      pharmacological and transgenic approaches to examine the relative contribution of
      mGluR1/5 in LTP at excitatory synapses on O/A interneurons. Bath-application of
      the selective mGluR1/5 agonist (s)-3,5-dihydroxyphenylglycine (DHPG) induced LTP
      of compound excitatory postsynaptic potentials. DHPG-induced LTP was not
      prevented by application of either mGluR1 or mGluR5 antagonists, was still
      present in mGluR1 knockout mice, but was blocked by co-application of both
      antagonists. These results indicate that LTP can be induced at O/A interneuron
      synapses by either mGluR1 or mGluR5 activation. As previously reported for mGluR1
      dependent LTP, the mGluR5-dependent LTP was independent of N-methyl-d-aspartate
      receptors. Pairing DHPG application with postsynaptic depolarization induced
      mGluR1- and mGluR5-dependent LTP of minimally-evoked excitatory postsynaptic
      currents, which were composed of calcium-permeable AMPA receptor and
      presynaptically modulated by group II mGluRs, hence confirming that both forms of
      LTP occurred directly at interneuron excitatory synapses. These findings uncover
      a new mGluR5-dependent form of LTP at O/A interneuron synapses and indicate that
      activation of mGluR1 or mGluR5 is sufficient to induce LTP at these synapses.
      Thus, a rich repertoire of adaptive changes may take place at these interneuron
      synapses to regulate hippocampal feedback inhibition.

PMID- 18035503
TI  - Detection of prostate-specific antigen coupled to immunoglobulin M in prostate
      cancer patients.
AB  - BACKGROUND: Several reports indicate that the main biomarkers for liver and
      colorectal cancer circulating in the blood stream associate with immunoglobulin M
      (IgM) to form stable complexes that show increased diagnostic relevance compared
      to circulating free biomarkers. METHODS: To further investigate the association
      between cancer biomarkers and IgM, we assessed the presence of prostate-specific
      antigen (PSA) as IgM complexes in sera of patients with prostate cancer (PC) or
      benign prostatic hyperplasia (BPH) in comparison with PSA measurements. RESULTS:
      PSA-IgM levels were significantly elevated in 40% (20/50) and 12% (6/51) of PC
      and BPH patients, respectively, compared to 22% (11/50) and 29% (15/51) of PSA
      positive patients in the same groups. Detection of cancer markedly increased from
      22 to 60% by co-determination of both markers (30/50 patients). Significantly
      elevated levels of PSA-IgM were found in 13 out of 30 patients affected by PC
      with a PSA value between 4 and 10 ng/mL and only in 4 out of 34 BPH patients in
      the same PSA range. CONCLUSIONS: The results are the first evidence of the
      occurrence of PSA-IgM complexes in patients with prostate cancer. The gain
      achieved in cancer detection by using the combination of PSA and PSA-IgM suggests
      that PSA-IgM could be a complementary serological marker of prostate cancer.

PMID- 18035504
TI  - Elevated p53 and p21waf1 mRNA expression in blood lymphocytes from lung cancer
      patients with chemoresistance.
AB  - BACKGROUND: Clinical and experimental studies suggest that alteration of the
      expression level of the p53 gene and other damage responsive genes may be
      associated with chemoresistance in cancer patients. METHODS: The present study
      evaluated the differences of the basal levels of lymphocytic p53 and p21waf1 mRNA
      expression collected before receiving cisplatin-based chemotherapy between 48
      chemo-ineffective lung cancer patients and 39 chemo-effective lung cancer
      patients using an optimized semi-quantitative multiplex reverse transcriptase
      polymerase chain reaction (RT-PCR). RESULTS: The data indicated that the mean
      mRNA level of p53 gene in chemo-ineffective patients (0.66) was 26.9% higher than
      that of the chemo-effective patients (0.52) with statistical significance
      (P=0.03), and a significantly higher level of p21waf1 mRNA expression in the
      chemo-ineffective patients (P=0.03) was also observed. In addition, by the
      multiplex long quantitative PCR analysis, we demonstrated that chemo-ineffective
      and chemo-effective patients have similar amounts of UV damage on their p53 gene
      of lymphocyte DNA through equal UV treatment. CONCLUSION: Our results suggest
      that elevated levels of p53/p21waf1 mRNA in blood lymphocytes collected before
      chemotherapy may predict the chemoresponses of lung cancer patients.

PMID- 18035502
TI  - Prostaglandins are necessary and sufficient to induce contextual fear learning
      impairments after interleukin-1 beta injections into the dorsal hippocampus.
AB  - The intra-hippocampal administration of interleukin-1beta (IL-1beta) as well as
      the induction of elevated but physiological levels of IL-1beta within the
      hippocampus interferes with the formation of long-term memory. There is evidence
      suggesting that the induction of prostaglandin (PG) formation by IL-1beta is
      involved in impairments in working and spatial memory following IL-1beta. The
      present experiments extend these findings by showing that PGs are responsible for
      memory deficits in contextual fear conditioning that occur following IL-1beta
      injection into the dorsal hippocampus of Sprague-Dawley rats. Cyclooxygenase
      (COX) inhibition blocked the disruption in contextual fear conditioning produced
      by IL-1beta and COX inhibition alone also disrupted contextual memory, suggesting
      an inverted U-shaped relationship between PG levels and memory. In addition to
      demonstrating the necessity of PGs in IL-1beta-mediated memory deficits, we also
      show that PGs injected directly into the dorsal hippocampus are sufficient to
      impair context memory and significantly reduce post-conditioning levels of BDNF
      within the hippocampus, suggesting a possible mechanism for the memory-impairing
      effects of PGs.

PMID- 18035505
TI  - Advice to young behavioral and cognitive scientists.
AB  - Modeled on Medawar's Advice to a Young Scientist [Medawar, P.B., 1979. Advice to
      a Young Scientist. Basic Books, New York], this article provides advice to
      behavioral and cognitive scientists. An important guiding principle is that the
      study of comparative cognition and behavior are natural sciences tasked with
      explaining nature. The author advises young scientists to begin with a natural
      phenomenon and then bring it into the laboratory, rather than beginning in the
      laboratory and hoping for an application in nature. He suggests collaboration as
      a way to include research outside the scientist's normal competence. He then
      discusses several guides to good science. These guides include Tinbergen's
      [Tinbergen, N., 1963. On aims and methods of ethology. Zeitschrift fur
      Tierpsychologie, 20, 410-433. This journal was renamed Ethology in 1986. Also
      reprinted in Anim. Biol. 55, 297-321, 2005] four "why" questions, Platt's [Platt,
      J.R., 1964. Strong inference. Science 146, 347-353,
      (http://weber.ucsd.edu/~jmoore/courses/Platt1964.pdf)] notion of strong inference
      using multiple alternative hypotheses, and the idea that positive controls help
      scientists to follow Popper's [Popper, K.R., 1959. The Logic of Scientific
      Discovery. Basic Books, New York, p. 41] advice about disproving hypotheses. The
      author also recommends Strunk and White's [Strunk, W., White, E.B., 1979. The
      Elements of Style, third ed. Macmillan, New York] rules for sound writing, and he
      provides his personal advice on how to use the anticipation of peer review to
      improve research and how to decode editors' and reviewers' comments about
      submitted articles.

PMID- 18035506
TI  - Pilot study of an EST approach of the coccolithophorid Emiliania huxleyi during a
      virus infection.
AB  - Blooms of the coccolithophorid Emiliania huxleyi can be infected by viruses,
      which can lead to bloom-termination. This pilot study used an expressed sequence
      tag (EST) approach to get a first view of gene-expression changes that occur
      during viral infection of E. huxleyi. cDNA libraries were constructed from
      uninfected cultures and 6, 12, and 24 h after infection with E. huxleyi-specific
      virus 86 (EhV-86). From each library 60-90 ESTs were randomly selected and
      annotated manually with PhyloGena. Viral genes were identified using BLAST-Search
      of the known viral genome. The data of this study show, that 6 h after viral
      infection the algal transcriptome changed significantly although few viral
      transcripts were present. At this point, changes mainly concerned transcripts
      related to photosynthesis and protein metabolism. However, after 24 h viral
      transcripts were most abundant. Viral transcripts found at this stage of viral
      infection encode proteins involved in protein degradation, nucleic acid
      degradation, transcription and replication.

PMID- 18035507
TI  - Development of a PCR protocol for the detection of Aeromonas salmonicida in fish
      by amplification of the fstA (ferric siderophore receptor) gene.
AB  - The aims of the study were to evaluate a new PCR protocol designed to detect
      Aeromonas salmonicida in fish tissues and to develop a non-destructive method for
      the diagnosis of furunculosis. A set of primers (Fer3, Fer4), flanking a fragment
      of the fstA gene (coding for the ferric-siderophore receptor) was designed,
      showing to be sensitive and specific. When compared to PCR methods previously
      reported, the new protocol recognized all the 69 A. salmonicida strains
      evaluated, with no cross-reactions with the other bacterial species analysed.
      Sensitivity assays were performed in fish tissues seeded with serial dilutions of
      pure cultures of A. salmonicida and mixed cultures of this bacterium with Vibrio
      anguillarum and Aeromonas hydrophila. Detection limits obtained were of 60 and
      450 bacterial cells 100 mg(-1) of tissue, respectively. Mucus and blood were
      evaluated in order to develop a non-destructive tool to detect the pathogen. The
      detection limits in seeded mucus and blood samples were 2.5 x 10(2) and 1 x 10(5)
      bacterial cells mL(-1), respectively. When the method was used to detect A.
      salmonicida in asymptomatic wild salmon, four samples of mucus and six of blood
      were positive, corresponding to 6 out of the 31 fish examined, whereas only one
      of the samples resulted positive by culture methods. It is concluded that the PCR
      protocol evaluated is fast, specific and sensitive to detect A. salmonicida in
      infected and asymptomatic fish, and will be helpful for the control of the
      disease through the prompt detection of carriers within fish populations.

PMID- 18035508
TI  - Cedivac-FMD can be used according to a marker vaccine principle.
AB  - In this study, we investigated whether Cedivac-FMD, an emergency vaccine against
      foot-and-mouth disease (FMD), is suitable for use conjointly with a screening
      program intended to confirm freedom from disease in vaccinated herds based on
      evidence of virus replication in vaccinates. Different sets of sera were tested
      using the Ceditest FMDV-NS ELISA for the detection of antibodies against non
      structural proteins (NSPs) of FMD virus. During a vaccine safety study, serum
      samples were collected from 10 calves, 10 lambs and 10 piglets following
      administration of a double dose and a repeat dose of high payload trivalent
      Cedivac-FMD vaccine. All serum samples collected both 2 weeks following the
      administration of a double dose as well as those collected 2 weeks after the
      single dose booster (given 2 weeks after the double dose) were negative in the
      Ceditest FMDV-NS ELISA. In a series of vaccine potency experiments, serum samples
      were collected from 70 vaccinated cattle prior to and following exposure to
      infectious, homologous FMD virus. When testing cattle sera collected 4 weeks
      after vaccination with a regular dose of monovalent >6 PD(50) vaccines, 1 of 70
      animals tested positive in the NSP antibody ELISA. After infection with FMD
      virus, antibodies to NSP were detected in 59 of 70 vaccinated cattle and 27 of 28
      non-vaccinated control animals within 7 days. Cedivac-FMD vaccines do not induce
      NSP antibodies in cattle, pigs or sheep following administration of a double dose
      or a repeat dose. FMD-exposed animals can be detected in a vaccinated group
      within 7-14 days. Because Cedivac-FMD does not induce NSP antibodies, the
      principle of 'marker vaccine' applies.

PMID- 18035509
TI  - Modulating peripheral gonadotrophin levels affects follicular expression of mRNAs
      encoding insulin-like growth factors and receptors in sheep.
AB  - Evidence suggests that the insulin-like growth factor (IGF) system is involved in
      follicular growth and development in sheep. However, little information exists as
      to the role that key peripheral factors play in regulating the expression of IGF
      components within the follicle. The present study investigated the regulatory
      effects of FSH and LH on gene expression for IGF ligands and receptors in ovine
      follicles, using bovine follicular fluid (bFF) and gonadotrophin-releasing
      hormone antagonist (GnRHa) model systems to perturb endogenous gonadotrophin
      secretion. Gene expression studies were carried out using in-situ hybridisation
      with sheep-specific ribonucleotide probes. Treatment of ewes with bFF had no
      effect on IGF-I mRNA levels. However, IGF-II mRNA levels, particularly in small
      follicles, and follicular type II IGF-R gene expression significantly increased
      following bFF administration (P<0.001). Conversely, there was a significant
      (P<0.001) decrease in type I IGF-R mRNA levels after only 12h of bFF treatment,
      especially in healthy follicles, although this was transient and was followed by
      a significant (P<0.01) increase in gene expression levels by 60 h of bFF
      treatment. Treatment of ewes with GnRHa resulted in a significant increase in
      mRNA levels encoding IGF-I (P<0.001), IGF-II in early atretic and large follicles
      (P<0.05), and type II IGF-R in healthy and early atretic follicles (P<0.001). In
      contrast, GnRHa administration decreased type I IGF-R gene expression levels
      after 60 h of treatment (P<0.001). These data highlight the roles that endogenous
      FSH and LH play in regulating IGF ligand and receptor gene expression in the
      sheep follicle.

PMID- 18035510
TI  - Efficacy of the intralesional treatment with Chenopodium ambrosioides in the
      murine infection by Leishmania amazonensis.
AB  - AIM OF THE STUDY: Leishmaniasis, caused by protozoan from Leishmania genus, is an
      endemic disease in the tropical and subtropical regions of the world. The
      chemotherapy to this disease is not always effective and can cause several side
      effects. Chenopodium ambrosioides L. (Chenopodiaceae) is used by the native
      people in the treatment of cutaneous ulcers caused by different species of
      Leishmania. The aim of this study was to investigate the effect of the treatment
      with a hydroalcoholic crude extract (HCE) from the leaves of Chenopodium
      ambrosioides on the murine infection with Leishmania amazonensis. MATERIAL AND
      METHODS: The mice were treated for 4-6 weeks post-infection (p.i.) with HCE (5
      mg/kg) or meglumine antimoniate (Sb(v)) (28 mg/kg) either by the oral route, once
      a day, for 15 days or by five intralesional (IL) injections at intervals of 4
      days. The thickness of the infected paws was determined weekly and the parasite
      load evaluated in the draining lymph nodes (LN), the spleen and in the footpad
      after 7 weeks of infection. The nitric oxide (NO) production was evaluated in
      cultures with cells from peritoneum or LN. RESULTS: The IL treatment increased
      the NO production in the LN and peritoneum cultures and reduced the parasite load
      from the footpad, spleen and LN. On the other hand, the oral treatment decreased
      did alter neither the NO production nor the parasite load. CONCLUSIONS: IL HCE
      treatment was more efficient than the oral HCE treatment since the former was
      able to control the dissemination of infection. This effect can be due to either
      a direct leishmanicidal effect of HCE or the improvement in the NO production by
      HCE-stimulated macrophages. The results could justify the topical use of the
      Chenopodium ambrosioides' leaves in the treatment of the ulcers caused by
      Leishmania.

PMID- 18035511
TI  - A single-blinded pilot study assessing neurovascular contact by using high
      resolution MR imaging in patients with trigeminal neuralgia.
AB  - OBJECTIVE: To assess the feasibility and utility of high-resolution three
      dimensional magnetic resonance angiography (3D MRA) and contrast-enhanced 3D
      spoiled gradient-recalled imaging (3D SPGRI) for the purpose of visualization of
      neurovascular contact in trigeminal neuralgia (TN) patients. METHODS: Forty-five
      patients (25 males, 20 females; age range, 23-82 years; and mean age, 55.67+/
      18.23 years) with unilateral typical TN and 36 control subjects (21 males, 15
      females; age range, 25-85 years; mean age, 57.53+/-19.25 years) underwent high
      resolution 3D MRA and contrast-enhanced 3D SPGRI assessment. The images were
      reviewed by two experienced neuroradiologists who were blinded to the clinical
      details. The imaging results were compared with the operative findings in all the
      patients; additionally, the degree of neurovascular contact was compared between
      the two groups based on MR imaging. RESULTS: In 45 patients with unilateral
      typical TN, the use of 3D MRA in conjunction with the contrast-enhanced 3D SPGRI
      identified neurovascular contact in 40 of the 42 symptomatic nerves; the contact
      was verified surgically. Based on the surgical findings, the sensitivity and
      specificity of MR imaging were 95.20% and 100%, respectively. Based on MRI, the
      compressing vessel (artery, vein) was correctly identified in 32 of the 39 cases
      verified by microvascular decompression. There was good agreement (K=0.77; 95%
      confidence interval, 0.54-0.99) between the position (medial, lateral, superior,
      and inferior) of the compressing vessel relative to the trigeminal nerve as
      defined by MR imaging and the surgical findings. The rates of vascular contact
      with the trigeminal nerve as observed on MRI were 31.94%, 48.89%, and 88.9% in
      the control subjects, asymptomatic, and symptomatic side of patients,
      respectively. CONCLUSION: The combined use of high-resolution 3D MRA and contrast
      enhanced 3D SPGRI is an extremely sensitive and specific technique for
      demonstrating vascular contact with the trigeminal nerve in TN patients.

PMID- 18035512
TI  - Impact of sample preparation in peptide/protein profiling in human serum by MALDI
      TOF mass spectrometry.
AB  - The low molecular weight (LMW) serum proteome (<15 kDa) is the most generally
      informative from a medical point of view. Different sample pre-treatment
      approaches and devices for serum depletion in high-abundant proteins were tested
      in order to analyze, by MALDI-TOF-MS (both in "linear" and "reflectron"
      acquisition mode), the serum low molecular weight proteins/peptides. The best
      results in terms of detected ions number and abundance were obtained by using
      ultrafiltration of serum on 30 kDa molecular weight cut off membranes followed by
      miniaturized reverse-phase solid-phase extraction (mu-SPE) as sample pre
      treatment; this procedure yielded also satisfactory within-sample and sample-to
      sample repeatability (on both m/z values and peak intensity of the main
      observable ions). The procedure was finally applied to serum samples of breast
      cancer patients, and the relevant results compared to "normal" samples seem to be
      promising for the individuation of different profiles ("linear" and "reflectron"
      mode) and/or peptides capable of differentiating for malignancies ("reflectron"
      mode).

PMID- 18035513
TI  - Gonadotropin releasing hormone receptor gene and protein expression and
      immunohistochemical localization in bovine uterus and oviducts.
AB  - Recently GnRH, GnRH-R systems has been demonstrated in various extrahypothalamic
      and extrapituitary reproductive tissues in different mammalian species, where
      GnRH acts in an autocrine and or paracrine manner and modulates different
      biological processes. GnRH-R mRNA has also been demonstrated in bovine ovaries
      (follicle and corpus luteum) and normal and carcinogenic human
      endometrium/endometrial cells. This is the first study elucidating presence of
      GnRH-R mRNA and GnRH-R protein in bovine uterus and oviducts in follicular and
      luteal phases of the estrous cycle and further localizing the receptors to
      endometrial and oviductal epithelial cells. To our knowledge this is the first
      report demonstrating GnRH-R mRNA and protein in mammalian oviducts. We used gene
      specific primers and monoclonal GnRH-R antibody to test GnRH-R mRNA and GnRH-R
      protein through RT-PCR and immunobloting. Immunohistochemistry was employed to
      localize these receptors to endometrial and oviductal epithelial cells. GnRH-R
      mRNA and receptor protein were expressed at expected molecular weights of 920bp
      and 60kD, respectively. Densitometry analysis revealed that expression levels for
      GnRH-R protein in uterus and oviducts were similar to bovine pituitary. The
      presence of GnRH receptors in bovine uterus and oviducts is intriguing and it
      would be imperative to examine the functional role of this system in the
      regulation of reproductive processes.

PMID- 18035514
TI  - Overweight/obesity and cancer genesis: more than a biological link.
AB  - The classical view according to which overweight/obesity is related to cancer
      considers adipose tissue as an active and metabolic "organ", acting through
      endocrine, autocrine and paracrine processes. Consequently, it has been
      hypothesized, that genesis and progression of cancer may be caused by different
      biological factors acting through diverse mechanisms including changes in the
      synthesis and bioavailability of sex hormones, insulin resistance, release of
      growth factors and/or proinflammatory cytokines and abnormal energetic disposal
      and expenditure. We have shown that overweight/obesity can be experimentally
      induced by benzo[a]pyrene, a universal well characterized chemical pollutant and
      that overweight/obesity may in fact be caused by several types of chemical
      pollutants. In this paper we propose that in addition to the above hypothetical
      biological mechanisms, adipose tissue acts as a reservoir for lipophilic,
      liposoluble environmental carcinogens, so that chemical pollution may in fact
      generate both overweight/obesity and cancer. More precisely, we propose that many
      carcinogens, be they mutagens or promotors can be stored in the adipose tissue,
      be released at convenient dose in the blood circulation and therefore target
      peripheral tissues to induce carcinogenesis. Such carcinogens mainly include
      organochlorine pesticides and PCBs. Their association with an increased risk of
      cancer seems to be demonstrated for breast and prostate carcinoma, as well as for
      lymphoma, not only in obese patients, but also in normal weight or even leaner
      patients suggesting that the adipose tissue may act as a reservoir for
      environmental carcinogens in obese as well as in non-obese patients.

PMID- 18035515
TI  - [Factors to consider in managing drug interactions in clinical practice].
AB  - The huge number of drug interactions makes it impossible to memorize them all.
      Detecting them and preventing adverse effects requires the use of reference works
      or databases. There are numerous discordances between the so-called "reference"
      books and databases. Nonexistent and unconfirmed interactions are published. The
      wording of the "drug interactions" section of the summary of product
      characteristics (SCP) sometimes sheds very little light on the risks involved.
      The delay by AFSSAPS in updating its drug interaction thesaurus may present
      problems in clinical practice. It is essential to know the limitations of the
      computerized systems for detecting and reporting drug interactions.

PMID- 18035516
TI  - [Monocular blindness as the first symptom of Churg-Strauss syndrome].
AB  - BACKGROUND: Ocular involvement is considered to be less frequent in Churg-Strauss
      syndrome than in other vasculitides. CASE: We describe the case of a patient who
      presented with monocular blindness due to central retinal artery occlusion, as
      the first symptom of Churg-Strauss syndrome. DISCUSSION: Acute loss of vision in
      a patient with hypereosinophilia should suggest Churg-Strauss syndrome, among
      other diagnoses. Rapid and appropriate treatment to prevent the extension of the
      vasculitic process is essential.

PMID- 18035517
TI  - [Renal cell carcinoma and antiangiogenic therapies].
AB  - Until 2006, immunotherapy (interferon-alpha or interleukin 2) was the standard
      medical treatment for metastatic renal cell carcinoma (RCC), and its results were
      disappointing: despite a few cases of complete response with prolonged survival,
      median survival was one year. Better understanding of the molecular mechanisms of
      tumor angiogenesis, especially in clear cell carcinoma, has led to the
      development of multiple targeted therapies to inhibit key effectors: vascular
      endothelial growth factor (VEGF), VEGF receptor, and mTOR (target of rapamycin).
      Two inhibitors targeting several protein kinases, including the VEGF receptor,
      have increased progression-free survival in patients with metastatic RCC and are
      now commercially available: sunitinib (Sutent) as first-line treatment and
      sorafenib (Nexavar) as second-line treatment. These targeted therapies will
      certainly affect overall survival, but it is too early for any firm conclusions.
      Their side-effects, usually low or moderate, include asthenia, anorexia,
      diarrhea, hand-and-foot syndrome and hypertension. Optimal management is required
      to ensure prolonged exposure. Other drugs have been effective: bevacizumab
      (Avastin), a monoclonal antibody inhibiting VEGF, increases progression-free
      survival as second-line treatment, and temsirolimus (Torisel), an mTOR protein
      kinase inhibitor, increases overall survival in the population of patients with
      poor prognosis. These targeted drugs will serve as the basis for development of
      future therapeutic strategies.

PMID- 18035518
TI  - [Iloprost for the treatment of systemic sclerosis].
AB  - An imbalance between prostacyclin (PGI2) and thromboxane A2 is observed in
      patients with scleroderma. Iloprost is a stable analogue of PGI2 with a plasma
      half-life of 20-30 min. Intravenous iloprost is effective in the treatment of
      Raynaud's phenomenon related to scleroderma, decreasing the frequency and
      severity of attacks. It also appears useful for the treatment of digital ulcers.
      Inhaled iloprost is an effective treatment for NYHA class III pulmonary arterial
      hypertension, either idiopathic primary or associated with a particular
      condition, such as scleroderma. Intravenous iloprost improves kidney vasospasm in
      patients with scleroderma. The possible benefits of sequential intravenous
      iloprost on the natural course of scleroderma require further investigation.

PMID- 18035519
TI  - Residential cognitive therapy versus residential interpersonal therapy for social
      phobia: a randomized clinical trial.
AB  - Eighty patients meeting DSM-IV criteria for social phobia were randomly assigned
      to 10 weeks of residential cognitive therapy (RCT) or residential interpersonal
      therapy (RIPT). Subjects were assessed at pretreatment, midtreatment,
      posttreatment, and 1 year after end of treatment. The patients reported chronic,
      highly comorbid social phobia. Most had tried other treatments without success.
      Existing individual treatment protocols for cognitive therapy and interpersonal
      therapy were extensively modified for an integrated group, individual, and
      residential format. The RCT and RIPT patients improved significantly on the
      primary outcome measures from pre- to posttreatment. No significant differences
      were observed between treatments. Patients also completed three weekly secondary
      outcome measures; on one, social role security, RCT was superior to RIPT. The
      entire sample reported continued improvement from posttreatment to 1-year follow
      up, indicating that improvements were robust. RCT in the present trial was
      associated with less improvement compared to individual CT in other recent
      trials.

PMID- 18035520
TI  - ArchaeaTF: an integrated database of putative transcription factors in Archaea.
AB  - Identification of all the transcription factors (TFs) encoded in a given genome
      is a prerequisite for understanding transcriptional regulatory networks. Archaea
      are prokaryotes that constitute one of the three main branches of organisms with
      an astounding diversity of habitats. In this report, we establish the ArchaeaTF
      database to provide an integrated information resource about TFs in Archaea, such
      as basic characteristics, domain architectures, and sequence similarities against
      the linked databases. Through its Web interface, ArchaeaTF provides three
      different ways for users to retrieve the data: simple browse, keyword search, and
      BLAST search. Moreover, ArchaeaTF can serve as a useful platform for comparative
      genomics analysis of archaeal TFs since it implements a series of tools,
      including MUSCLE for multiple sequence alignments of the DNA-binding domains,
      QuickTree for phylogenetic tree construction, and OrthoMCL for ortholog
      identification. The released ArchaeaTF 1.0 contains 2135 putative TFs from 37
      completed archaeal genomes. In conclusion, we believe that ArchaeaTF will be a
      useful resource and convenient platform for researchers working on TFs and
      transcriptional regulatory networks to retrieve information from TFs in Archaea
      rapidly. ArchaeaTF is accessible at http://bioinformatics.zj.cn/archaeatf.

PMID- 18035521
TI  - Multifaceted transcriptional regulation of the murine intestinal mucus layer by
      endogenous microbiota.
AB  - The intestinal mucus layer and endogenous microbiota are strongly intertwined and
      this contributes to the maintenance of the epithelial barrier and ultimately of
      gut homeostasis. To understand the molecular foundations of such relationship, we
      investigated if the nature of the microbiota transcriptionally regulates mucus
      layer composition in vivo. We found that the expression of mucins 1 to 4 and
      trefoil factor 3 was down-regulated in the ileum and colon of conventional and
      reconventionalized mice compared with germ-free animals. Conversely, very limited
      colon-restricted changes in transmembrane mucins were detected in mice colonized
      with human adult or baby microbiota. Moreover, by microarray analysis, the murine
      endogenous microbiota was found to modulate genes putatively involved in mucin
      secretion. These findings show that a well-established microbial community
      participates in the regulation of the gut mucus layer and that its composition
      and adequacy to the host are key factors in this process.

PMID- 18035522
TI  - Medial tongue cleft associated with intraoral hamartoma--case report and review
      of literature.
AB  - A newborn female was referred with the following clinical symptoms: median tongue
      cleft, palate cleft, ankyloglosson, sublingual intraoral hamartoma and palatal
      intraoral hamartoma. Magnetic resonance imaging showed a subcutaneous cyst
      overlying the manubrium sterni. Genetic investigation (chromosome analysis)
      showed no aberrations and/or variations. The quick growth of the intraoral
      hamartoma required an excision at the age of 3 months. Under general anaesthesia
      the intraoral hamartoma was excised and the median tongue cleft was closed.
      Median tongue clefts are reported to be only associated with orofacial digital
      syndromes type I, II, IV and VI. If the clinical appearance is described without
      any association to an orofacial syndrome, the Tessier 30 cleft definition could
      be used as the best explanation of the symptoms. This is the first description of
      a combination of tongue cleft, palate cleft, intraoral hamartoma and subcutaneous
      cyst overlying the manubrium sterni. The clinical symptoms of this patient can be
      described best as a mild form of an orofacial digital syndrome type II or
      variation of a Tessier cleft No. 30.

PMID- 18035523
TI  - Neural correlates of musicogenic epilepsy: SISCOM and FDG-PET.
AB  - To localize the neural correlates of musicogenic epilepsy, subtraction ictal
      SPECT coregistered with MRI (SISCOM) and (18)F-fluorodeoxy glucose positron
      emission tomography (FDG-PET) were performed in a woman who had suffered from
      frequent musicogenic seizures. She had complex partial seizures consisting of
      palpitation and an unpleasant feeling, which were followed by staring and
      oroalimentary automatisms. Ictal EEG showed rhythmic theta waves originated from
      the right temporal lobe, and SISCOM showed ictal hyperperfusion on right insula,
      amygdala, hippocampal head, and anterior temporal lobe, whereas interictal FDG
      PET showed interictal hypometabolism in the same brain regions, suggesting
      dysfunction and abnormal activation of right temporo-limbic structures related to
      an emotional response to music.

PMID- 18035524
TI  - Bile salt-phospholipid aggregation at submicellar concentrations.
AB  - The aggregation behavior of the bile salts taurodeoxycholate (NaTDC) and sodium
      cholate (NaC), are followed at concentrations below critical micelle
      concentrations (CMCs) using the environment sensitive, fluorescent-labeled
      phospholipid, 2-(6-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl-1
      hexadecanoyl-sn-glycero-3-phosphocholine (NBD-C(6)-HPC). A buffer solution
      containing NBD-C(6)-HPC is titrated with increasing NaC or NaTDC and the
      fluorescence changes followed. Both bile salts induced fluorescence changes below
      their critical micelle concentration indicating the presence of a bile salt
      phospholipid aggregate. A critical control experiment using 6-(N-(7-nitrobenz-2
      oxa-1,3-diazol-4-yl)amino) hexanoic acid (NBD-X) shows that the bile salts are
      interacting with the longer, C16 hydrocarbon tail, not the NBD probe. The
      fluorescence curves were fitted to the Hill equation as a model for cooperative
      aggregation. The cooperativity model provides a minimum estimate for the number
      of bile salts to give maximal fluorescence. This number was calculated for NaC
      and NaTDC to have a minimum value of approximately 2. A small aggregation number
      supports the existence of primary micellar aggregates at submicellar
      concentrations for bile salt-phospholipid aqueous solutions.

PMID- 18035525
TI  - Evaluation of in vitro in vivo correlations for dry powder inhaler delivery using
      artificial neural networks.
AB  - The aim of these experiments was to investigate the use of artificial neural
      networks (ANNs) for generating models able to predict the relative lung
      bioavailability and clinical effect of salbutamol when delivered to healthy
      volunteers and asthmatic patients from dry powder inhalers (DPIs). ANN software
      was used to model in vitro, demographic and in vivo data from human subjects for
      four different DPI formulations containing salbutamol sulfate. In 12 volunteers,
      a model linking the in vitro aerodynamic characteristics of the emitted dose and
      volunteer body surface area with the urinary excretion of drug and its metabolite
      in the 24h period after inhalation was established. In 11 mild asthmatics, a
      predictive model correlating in vitro data, baseline lung function, body surface
      area and age with post-treatment improvements in forced expiratory volume in 1s
      (FEV1) was also generated. Models validated using unseen data from individual
      subjects receiving the different DPI formulations were shown to give predictions
      of in vivo performance. The squared correlation coefficients (R2) for plots
      comparing predicted and observed in vivo outcomes were 0.83 and 0.84 for urinary
      excretion and lung function data, respectively. It can therefore be concluded
      that ANN models have the potential to predict the in vivo performance of DPIs in
      individual subjects.

PMID- 18035526
TI  - How do high-level specifications of the brain relate to variational approaches?
AB  - High-level specification of how the brain represents and categorizes the causes
      of its sensory input allows to link "what is to be done" (perceptual task) with
      "how to do it" (neural network calculation). In this article, we describe how the
      variational framework, which encountered a large success in modeling computer
      vision tasks, has some interesting relationships, at a mesoscopic scale, with
      computational neuroscience. We focus on cortical map computations such that "what
      is to be done" can be represented as a variational approach, i.e., an
      optimization problem defined over a continuous functional space. In particular,
      generalizing some existing results, we show how a general variational approach
      can be solved by an analog neural network with a given architecture and
      conversely. Numerical experiments are provided as an illustration of this general
      framework, which is a promising framework for modeling macro-behaviors in
      computational neuroscience.

PMID- 18035527
TI  - Enhanced skin penetration of P20 phosphopeptide using protein transduction
      domains.
AB  - Protein transduction domains (PTDs) were recently demonstrated to increase the
      penetration of the model peptide P20 when the PTD and P20 were covalently
      attached. Here, we evaluated whether non-covalently linked PTDs were capable of
      increasing the skin penetration of P20. Two different PTDs were studied: YARA and
      WLR. Porcine ear skin mounted in a Franz diffusion cell was used to assess the
      penetration of P20 in the stratum corneum (SC) and viable skin (VS); VS consists
      of dermis and epidermis without SC. The transdermal delivery of P20 was also
      assessed. At 1mM, YARA promoted a 2.33-fold increase in the retention of P20 in
      the SC but did not significantly increase the amount of P20 that reached VS. WLR
      significantly increased (2.88-fold) the penetration of P20 in VS. Compared to the
      non-attached form, the covalently linked WLR fragment was two times more
      effective in promoting the penetration of P20 into VS. None of the PTDs promoted
      transdermal delivery of P20 at 4h post-application. It was concluded that
      selected non-covalently linked PTDs can be used as a penetration enhancer, but
      greater skin penetration efficiency can be achieved by covalently binding the PTD
      to the therapeutic agent.

PMID- 18035528
TI  - Saprotrophy of Conidiobolus and Basidiobolus in leaf litter.
AB  - This study of the putative saprotrophs of Conidiobolus and Basidiobolus aids the
      understanding of their ecological roles in litter, and their relationship with
      the entomogenous fungi of the Entomophthorales. A total of 47 isolates (ten spp.)
      were screened for their ability to utilise pure compounds, arthropod cadavers,
      and plant leaf fragments as substrates. Isolates co-occurred in a larch
      plantation (Larix sp.) or were from adjacent habitats. Of the 21 isolates (nine
      spp.) tested on potential prime carbon sources, none could utilise common plant
      structural polymers. Conidiobolus adiaeretus, C. iuxtagenitus, and B. ranarum
      from litter and some soil isolates of C. heterosporus, C. pumilus, and C.
      firmipilleus could use starches and glycogen. In marked contrast, all could
      utilise animal chitin, gelatine, casein, N-acetyl glucosamine, and trehalose. The
      lipids tributyrin and sunflower oil also supported growth. Conidia on cadavers
      usually led to high levels of colonisation as was the case for 30 isolates (ten
      species). Collembola were more frequently and rapidly colonised than mites.
      Cadavers of many other arthropods were also internally colonised. The ability to
      utilise cadavers of diverse arthropods indicates that trophic competition between
      co-occurring test species may be minimal. Niche differentiation may depend more
      on non-trophic features of their life history. Negative correlation of
      performance with the presence of naturally occurring, non-test fungi suggests
      competition with (or antibiosis from) at least some of the other fungi. In washed
      or unwashed plant fragments of larch litter (F-layer) only occasional local
      growth and resting spore formation occurred. Extra nutrients did not facilitate
      colonisation. Alternative forms of repetitional conidia showed a strong
      association with plant fragments but not with cadavers.

PMID- 18035530
TI  - Modeling of substrate degradation and oxygen consumption in waste composting
      processes.
AB  - A multi-component modeling system was developed to simulate substrate degradation
      and oxygen consumption in waste composting processes. Levels of soluble substrate
      (Ss), insoluble substrate (Si), active biomass (X), inert material, moisture,
      temperature, and oxygen concentration were considered as state variables. The
      relationships among these variables were also incorporated within the modeling
      framework. Three conversion reactions, including growth of aerobic biomass, decay
      of aerobic biomass, and solubilisation of insoluble substrate, were considered in
      the simulation system. The modeling inputs included temperature, moisture, oxygen
      concentration, and initial conditions of the state variables, while the outputs
      included oxygen uptake accumulation (OUA), oxygen uptake rate (OUR), Ss, Si, and
      X for representing the substrate degradation and oxygen consumption status. The
      effectiveness of the developed model was demonstrated through its application to
      a case study in a 30L vessel over 200h. Through verification-based composting
      experiments, it was shown that the modeling solutions were consistent with the
      experimental results with an acceptable accuracy level. Sensitivity analyses of
      the model showed that an increased maximum microbial growth rate would result in
      raised OUA, OUR, Ss, and X levels; a decreased biomass decay rate constant would
      help enhance the composting process. Moreover, variations in the maximum growth
      rate would affect the composting process more significantly than those of the
      biomass decay rate constant.

PMID- 18035529
TI  - Mechanisms controlling cell cycle exit upon terminal differentiation.
AB  - Coordinating terminal differentiation with permanent exit from the cell cycle is
      crucial for proper organogenesis, yet how the cell cycle is blocked in
      differentiated tissues remains unclear. Important roles for retinoblastoma family
      proteins and Cyclin-dependent kinase inhibitors have been delineated, but in many
      cases it remains unclear what triggers cell cycle exit. This review focuses on
      describing recent advances in deciphering how terminal differentiation and exit
      from the cell cycle are coordinated.

PMID- 18035531
TI  - Novel highly-performing immunosensor-based strategy for ochratoxin A detection in
      wine samples.
AB  - The increasing concern about ochratoxin A (OTA) contamination of different food
      and feedstuffs demands high-performing detection techniques for quality
      assessment. Two indirect competitive enzyme-linked immunosorbent assay (ELISA)
      strategies were investigated for the development of OTA electrochemical
      immunosensors based on different OTA immobilisation procedures. Immunosensors
      based on avidin/biotin-OTA showed enhanced performance characteristics compared
      to those based on the adsorption of bovine serum albumin (BSA)-OTA conjugate.
      Performance of polyclonal (PAb) and monoclonal (MAb) antibodies against OTA was
      compared, showing at least one-order of magnitude lower IC(50) values when
      working with MAb. Alkaline phosphatase (ALP)- and horseradish peroxidase (HRP)
      labelled secondary antibodies were evaluated. Both conjugates led to similar
      results when working with OTA standard solutions in buffer. However, whereas
      electroactive interferences present in spiked wine samples did not affect HRP
      labelled immunosensors (4% slope deviation), they were likely oxidised at 0.225 V
      versus Ag/AgCl, the working potential for ALP-labelled immunosensors (25% slope
      deviation). Considering 80% of antibody binding as the limit of detection, values
      of 0.7 and 0.3 ng/mL for HRP- and ALP-labelled immunosensors respectively,
      validate these immunosensors as useful screening tools to assess OTA levels in
      wine.

PMID- 18035532
TI  - Drug discovery beyond the 'rule-of-five'.
AB  - Although a very useful guideline for orally bioavailable small-molecule drug
      design, the 'rule-of-five' (also known as 'Lipinski's rule of drug-likeness') has
      to some extent been overemphasized. Firstly, only 51% of all FDA-approved small
      molecule drugs are both used orally and comply with the 'rule-of-five'. This does
      not even include the increasing number of biologicals of which several have
      reached 'blockbuster' status. Secondly, it does not cover natural product and
      semisynthetic natural product drugs, which constitute over one-third of all
      marketed small-molecule drugs. A more balanced and programmatic approach to drug
      discovery should be more productive than to rely on an overemphasis of 'rule-of
      five' compliance. Rather it should consider proactively the development of
      parenteral drugs in parallel to oral drugs and to consider the development of
      therapeutic antibodies in parallel to small-molecule drugs. These are
      particularly relevant for efforts against 'first-in-class' and/or particularly
      challenging targets such as proteases and those involving protein-protein
      interactions. In addition, more effort should be invested in natural product
      research. Emerging novel technologies such as synthetic biology (genetic
      engineering of living organisms to produce small-molecule therapeutics) may
      address several challenging issues of natural product-based drug discovery
      including synthetic feasibility and ligand efficiency.

PMID- 18035533
TI  - Invasive lobular carcinoma of the breast: response to hormonal therapy and
      outcomes.
AB  - Invasive lobular carcinoma (ILC) comprises approximately 5-15% of breast cancers
      and appears to have a distinct biology. It is less common than invasive ductal
      carcinoma (IDC) and few large studies have addressed its biologic characteristics
      and behaviour with respect to long-term clinical outcome and response to adjuvant
      therapy. METHODS: This study is based on a large and well-characterised
      consecutive series of invasive breast carcinomas with a long-term follow-up (up
      to 25 years). This series included 415 (8%) patients with pure ILC and 2901
      (55.7%) with IDC (not otherwise specified) identified from a consecutive cohort
      of 5680 breast tumours presented to our Breast Unit that were treated in a
      similar conventional manner. Clinicopathological, therapy and outcome information
      as well as data on a large panel of biomarkers were available. RESULTS: Compared
      to IDC, patients with ILC tended to be older and present with tumours which are
      more frequently lower grade (typically, grade 2 [84%]), hormone-receptor positive
      (86% compared to 61% in IDC), of larger size, and with the absence of vascular
      invasion. A higher frequency of ILC was placed in the good Nottingham Prognostic
      Index group (40% compared to 21% in IDC). ILC showed indolent but progressive
      behavioural characteristics with nearly linear survival curves which crossed
      those of IDC after approximately 10years of follow-up, thus eventually exhibiting
      a worse long-term outcome. Importantly, ILC showed a better response to adjuvant
      hormonal therapy (HT) with improvement in survival in patients who received HT
      compared with matched patients with IDC. CONCLUSION: ILC is a distinct entity of
      breast cancer that responds well to adjuvant HT. These data add important
      clinical information for assessing the long-term benefits of adjuvant HT use in
      ILC.

PMID- 18035534
TI  - Long-term survivors of adult cancers and uptake of primary health services: a
      systematic review.
AB  - AIM: The aim of this paper is to systematically review the literature on the use
      of primary and community care services by long-term survivors of adult cancers.
      METHODS: We conducted a systematic search of eight databases and considered
      papers looking at primary care aspects of surviving cancer at least 3 years past
      diagnosis. RESULTS: Ten eligible papers in four categories: consultation rates in
      primary care, cancer screening, use of preventative services and chronic disease
      management. There was no conclusive evidence that cancer survivors have increased
      rates of consultation in primary care. The studies reported that cancer screening
      is well managed in survivors. Preventative and chronic care is worse in long-term
      colorectal cancer survivors compared with long-term breast cancer survivors and
      controls. CONCLUSION: We found little research, especially outside the United
      States, relating to the care of long-term cancer survivors in primary care.
      Future work should examine screening for treatment-specific sequelae and the
      quality of care for co-morbid disease.

PMID- 18035535
TI  - Introduction.

PMID- 18035536
TI  - Laparoscopic rectal resection with intraoperative radiotherapy in locally
      advanced cancer: preliminary results.
AB  - Carcinoma of the rectum is a common malignancy, especially in developed
      countries. The main stay of the therapy for rectal cancer is radical surgery.
      Total mesorectal excision has emerged as the surgical technique that can
      substantially reduce local recurrences. The laparoscopic approach does not seem
      to entail any oncologic disadvantages. Radiotherapy (RT) alone is capable of
      eradicating some localized rectal tumors while its effect on larger tumors is
      limited by normal tissue tolerance, tumor sensitivity and microscopic spread
      beyond the primary site. Preoperative chemoradiation has potential advantages.
      The rationale for combining cytotoxic agents and RT is based on the ability of
      some drugs to act as an enhancer of RT. Preoperative chemoradiation can
      potentially downstage tumors to facilitate surgery, reduce the risk of tumor
      seeding, problems with hypoxia which is increased postoperatively, allowing more
      optimal tumor cell kill for equivalent doses compared to postoperative
      radiotherapy. The addition of radiation to surgery has been successfully used in
      many disease sites. In the intraoperative radiotherapy (IOERT), a high dose to
      the area of highest risk for tumor cell persistence is delivered while dose
      limiting structures such as small bowel, bladder, or ureters can be mechanically
      excluded. Our preliminary experience shows that laparoscopic rectal resection
      with IOERT is not only feasible, but associates oncologic radical treatment with
      important advantages of laparoscopic approach.

PMID- 18035537
TI  - Experimental therapeutic approaches to adenocarcinoma: the potential of tumor
      cells engineered to express MHC class II molecules combined with naked DNA
      interleukin-12 gene transfer.
AB  - We have previously shown that TS/A murine mammary adenocarcinoma cells, induced
      to express high surface expression of MHC class II molecules by stable
      transfection of CIITA, resulted in high rate (92%) of tumor rejection and tumor
      immunity to subsequent homologous tumor challenges. The immunological basis of
      tumor response is based on tumor-specific CD4(+) T helper type 1 (Th1) in the
      priming phase and tumor-specific CD8(+) T cells as the major effector cells. IL
      12 is the crucial cytokine that drives Th1 polarization in conjunction with
      inducing strong cellular-based immune responses. We have previously shown in the
      same tumor model that a naked DNA IL-12 gene transfer was effective in preventing
      tumor angiogenesis in an immunopreventive approach when administrated at least 2
      days prior to the tumor inoculation. Here we indicate that the combination of the
      two approaches in immunotherapy of established tumors is efficacious in delaying
      tumor growth but not in completely eradicating the tumor.

PMID- 18035538
TI  - Colorectal cancer: the role of laparoscopy.
AB  - Since the first report in 1991 the laparoscopic resection of colon cancer is
      progressing slowly and just in the last 2-3 years is becoming more popular. The
      resistance to its use by some general and colo-rectal surgeons is receding. The
      explanations are that technology is evolving quickly and there is a worldwide
      diffusion of more sophisticated surgical instruments. Moreover several randomized
      trials have been published showing that the outcomes of laparoscopic colon
      surgery are similar or better than those of conventional surgery and the early
      reports suggesting the tumour dissemination were not confirmed. The revolution in
      oncological surgery that we are observing in these last decades with the
      introduction and diffusion of mini-invasive approach is comparable to that
      regarding conventional surgery during the period of Halsted. Therefore the
      principles of surgery accepted during the years must not be forgotten.

PMID- 18035539
TI  - Radius surgical system and conventional laparoscopic instruments in abdominal
      surgery: application, learning curve and ergonomy.
AB  - We illustrate our experience with a new class of instruments, the mechanical
      manipulators (MM), whose main features are an improved mobility, and ergonomy and
      a modular structure. A specific MM, the Radius Surgical System (RADIUS), has been
      used both for educational purposes as well as in clinical studies, demonstrating
      that it can represent an efficient tool to support surgeons performing surgical
      complex procedures, with a short learning curve for the postural attitude.

PMID- 18035540
TI  - Spinal anaesthesia with a micro-catheter in high-risk patients undergoing
      colorectal cancer and other major abdominal surgery.
AB  - Extended spinal anaesthesia using a spinal micro-catheter was used as a primary
      method of anaesthesia for elective colorectal cancer surgery in 68 high risk
      patients over a 14-year period in our institution. The technique was also useful
      in eight elective and 13 emergency abdominal surgeries. All patients suffered
      from severe chronic obstructive airway disease requiring multiple inhalers and
      drugs (ASA III). Thirty nine of these patients also suffered from angina,
      myocardial infarction, diabetes and other systemic diseases (ASA IV). Surgery
      included right hemicolectomy, left hemicolectomy, total colectomy, sigmoid
      colectomy, Hartman's resection, anterior resection of rectum, abdominoperineal
      resection, cholecystectomy (open and laparoscopic) and obstructed inguinal hernia
      requiring laparotomy. Spinal anaesthesia was performed under strict aseptic
      conditions with a 22 gauge spinal needle with a mixture consisting of 2.75ml of
      0.5% heavy bupivacaine and 0.25ml of fentanyl (25microg). This was followed by
      placement of a spinal micro-catheter and the duration of anaesthesia was extended
      by intermittent injection of 0.5% isobaric bupivacaine. Brief hypotension
      occurred in 12.4% of patients during the establishment of anaesthetic block
      height to T6-7 and was duly treated with intravenous administration of fluid and
      ephedrine hydrochloride. Good anaesthesia resulted in all patients except for
      brief discomfort in some patients during hemicolectomy surgery possibly due to
      the dissection and traction on the peritoneum causing irritation to the
      diaphragm. The use of sedation was avoided. General anaesthesia was administered
      in one patient and this patient required postoperative ventilation and
      cardiovascular support in the Intensive Care Unit. The spinal micro-catheter was
      removed at the end of surgery. Postoperative pain relief was obtained by
      administering intravenous morphine through a patient controlled analgesia machine
      in the critical care ward area (High Dependency Unit). There was a low incidence
      of minor postoperative side effects such as nausea (14.6%), vomiting (7.9%),
      minor post dural puncture headache (5.6%) and pruritus (5.6%). We conclude that
      spinal anaesthesia with a micro-catheter may be used as a primary method of
      anaesthesia for colorectal cancer surgery and other major abdominal surgery in
      high-risk patients for whom general anaesthesia would be associated with higher
      morbidity and mortality.

PMID- 18035541
TI  - Mammography: interobserver variability in breast density assessment.
AB  - Our objective was to determine the interobserver variability of breast density
      assessment according to the Breast Imaging Reporting and Data System (BI-RADS)
      and to examine potential associations between breast density and risk factors for
      breast cancer. Four experienced breast radiologists received instructions
      regarding the use of BI-RADS and they assessed 57 mammograms into BI-RADS density
      categories of 1-4. The weighted kappa values for breast density between pairs of
      observers were 0.84 (A, B) (almost perfect agreement); 0.75 (A, C), 0.74 (A, D),
      0.71 (B, C), 0.77 (B, D), 0.65 (C, D) (substantial agreement). The weighted
      overall kappa, measured by the intraclass correlation coefficient (ICC), was 0.77
      (95% CI: 0.69-0.85). Body mass index was inversely associated with high breast
      density. In conclusion, overall interobserver agreement in mammographic
      interpretation of breast density is substantial and therefore, the BI-RADS
      classification for breast density is useful for standardization in a multicentre
      study.

PMID- 18035542
TI  - Synthesis, cytotoxic evaluation, and DNA binding of novel thiazolo[5,4
      b]quinoline derivatives.
AB  - A series of novel alkylamino and 9-anilinothiazolo[5,4-b]quinolines were
      synthesized as potential antitumoral agents. The in vitro cytotoxicity of these
      compounds was evaluated on several cell lines. The inclusion of electron
      withdrawn/acceptor hydrogen-bond groups at position 3' of the anilino ring and
      the presence of an alkylamino chain on the tricyclic framework (regardless of its
      position) seem to be structural features relevant to cytotoxic activity.

PMID- 18035544
TI  - Synthesis and structure-activity relationships of a series of substituted 2-(1H
      furo[2,3-g]indazol-1-yl)ethylamine derivatives as 5-HT2C receptor agonists.
AB  - A series of novel indazole derivatives were synthesized, and their structure
      activity relationships examined in order to identify potent and selective 5-HT2C
      receptor agonists. Among these compounds, (S)-2-(7-ethyl-1H-furo[2,3-g]indazol-1
      yl)-1-methylethylamine (YM348) had a good in vitro profile, that is, high
      agonistic activity to the human 5-HT2C receptor subtype (EC50 = 1.0 nM) and high
      selectivity over 5-HT2A receptors. This compound was also effective in a rat
      penile erection model when administered p.o.

PMID- 18035543
TI  - Estradiol and estrone C-16 derivatives as inhibitors of type 1 17beta
      hydroxysteroid dehydrogenase: blocking of ER+ breast cancer cell proliferation
      induced by estrone.
AB  - Estrogens play an important role in the development of breast cancer. Inhibiting
      17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1)--the enzyme responsible
      for the last step in the biosynthesis of the most potent estrogen, estradiol (E2)
      -would thus allow hindering the growth of estrogen-sensitive tumors. Based on a
      previous study identifying 16beta-benzyl-E2 (1) as a lead compound for developing
      inhibitors of the transformation of estrone (E1) into E2, we modified the benzyl
      group of 1 to improve its inhibitory activity. Three strategies were also devised
      to produce compounds with less residual estrogenic activity: (1) replacing the
      hydroxy group by a hydrogen at position 3 (C3); (2) adding a methoxy at C2; and
      (3) adding an alkylamide chain known to be antiestrogenic at C7. In order to test
      the inhibitory potency of the new compounds, we used the human breast cancer cell
      line T-47D, which exerts a strong endogenous 17beta-HSD1 activity. In this intact
      cell model, 16beta-m-carbamoylbenzyl-E2 (4m) emerged as a potent inhibitor of
      17beta-HSD1 with an IC50 value of 44 nM for the transformation of [14C]-E1 (60
      nM) into [14C]-E2 (24-h incubation). In another assay aimed at assessing the
      unwanted estrogenic activity, a 10-day treatment with 4m at a concentration of
      0.5 microM induced some proliferation (38%) of T-47D estrogen-sensitive (ER+)
      breast cancer cells. Interestingly, when 4m (0.5 microM) was given with E1 (0.1
      nM) in a 10-day treatment, it blocked 62% of the T-47D cell proliferation induced
      by E1 after its reduction to E2 by 17beta-HSD1. Thus, in addition to generating
      useful structure-activity relationships for the development of 17beta-HSD1
      inhibitors, our study demonstrates that using such inhibitors is a valuable
      strategy for reducing the level of E2 and consequently its proliferative effect
      in T-47D ER+ breast cancer cells.

PMID- 18035545
TI  - Imidazo[1,2-a]pyridine derivatives as inhibitors of TNF-alpha expression in T
      cells.
AB  - Novel hexahydroimidazo[1,2-a]pyridines prepared by the addition of ethyl (1
      benzylimidazolidin-2-ylidene)acetate (2) to the fungal metabolite podoscyphic
      acid (1a) and esters of 1a have been evaluated for their ability to inhibit the
      inducible TNF-alpha promoter activity in T cells. The methyl ester 3b is the most
      potent, inhibiting the TNF-alpha driven reporter gene expression in Jurkat T
      cells with an IC(50)-value of 2.0 microg/ml (3.6 microM). In addition, compound
      3b inhibited the inducible TNF-alpha production in the myelomonocytic U937 cells
      with an IC(50)-value of 4.6 microM.

PMID- 18035546
TI  - New terpenoids from Maytenus apurimacensis as MDR reversal agents in the parasite
      Leishmania.
AB  - Two new sesquiterpenes (1-2) and one new lupane triterpene (3) have been isolated
      from the roots of Maytenus apurimacensis. The novel beta-dihydroagarofurans are
      the first sesquiterpenes with a basic polyhydroxy skeleton of 15-deoxyalatol and
      4,15-dideoxyalatol that show high MDR reversing activity in the protozoan
      parasite Leishmania tropica.

PMID- 18035547
TI  - X-ray imaging with the PILATUS 100k detector.
AB  - We report on the application of the PILATUS 100K pixel detector for medical
      imaging. Experimental results are presented in the form of X-ray radiographs
      using standard X-ray absorption contrast and a recently developed phase contrast
      imaging method. The results obtained with the PILATUS detector are compared to
      results obtained with a conventional X-ray imaging system consisting of an X-ray
      scintillation screen, lens optics, and a charge coupled device. Finally, the
      results for both systems are discussed more quantitatively based on an image
      power spectrum analysis.

PMID- 18035548
TI  - Long-term potentiation of high-frequency oscillation and synaptic transmission
      characterize in vitro NMDA receptor-dependent epileptogenesis in the hippocampus.
AB  - The implication of high-frequency network oscillations (HFOs) in brain pathology
      resides in as yet unclear mechanisms. Employing field recordings from ventral
      hippocampal slices and two models of epileptogenesis (i.e. establishment of
      interictal-like persistent bursts), we found that HFOs associated with
      epileptiform bursts and excitatory synaptic transmission were co-modulated during
      epileptogenesis. NMDA receptor-dependent epileptogenesis in CA3 was consistently
      accompanied by long-lasting strengthening in synaptic transmission (by 94+/-17%,
      n=5) and HFOs (frequency, power and duration increased by 24+/-8%, 57+/-18% and
      33+/-10%, respectively). Co-modulation of synaptic transmission and HFOs was also
      observed in NMDA receptor-independent epileptogenesis, although in individual
      experiments either enhancement or depression of both phenomena was observed.
      Pathological HFOs >200 Hz were unequivocally present in persistent bursts induced
      by NMDA receptor-dependent but not NMDA receptor-independent mechanisms. The
      duration of pathological HFOs associated with persistent bursts but not of HFOs
      associated with bursts before the establishment of epileptogenesis was linearly
      and strongly correlated with the duration of bursts (r=0.58, P<0.0001). We
      propose that interplay between spontaneous synchronous bursting and long-lasting
      synaptic potentiation accompanying certain forms of epileptogenesis may underlie
      long-lasting potentiation of HFOs, whose quantitative aspects may reliably signal
      the degree of network changes involved in epileptogenesis.

PMID- 18035549
TI  - Molecular cloning, expression profile and promoter analysis of a novel ethylene
      responsive transcription factor gene GhERF4 from cotton (Gossypium hirstum).
AB  - Ethylene-responsive element binding factors (ERFs) are plant-specific
      transcription factors, many of which have been linked to stress responses. A
      novel ERF gene, designated GhERF4, was isolated by RACE-PCR from Gossypium
      hirsutum. The GhERF4 cDNA has a total length of 1061bp with an open reading frame
      of 669bp, encoding a protein of 222 amino acids with a molecular weight of
      23.5kDa and a calculated pI of 9.03. Sequence alignment shows that GhERF4
      contains a 58 amino acid long AP2/ERF domain and a RKRP nuclear localization
      signal, and belongs to a group II protein in the ERF subfamily as typified by the
      C-terminal ERF-associated Amphiphilic Repression (EAR) motif. Southern blot
      analysis indicates that GhERF4 is a single copy gene in cotton genome. Using
      green fluorescent protein fusion, we demonstrate that GhERF4 accumulates
      specifically in the nucleus of onion epidermis cells. Semi-quantitative RT-PCR
      reveals that GhERF4 is constitutively expressed in true leaves, roots, seeds and
      stems. The transcripts of GhERF4 accumulate highly and rapidly when plants are
      treated with exogenous ethylene, salt, cold, drought stresses and exogenous
      abscisic acid (ABA) treatment, suggesting that GhERF4 is regulated by certain
      components of the stress signaling pathway. Promoter analysis indicates that the
      5' upstream region of GhERF4 possesses some elements induced by physiological and
      environmental factors. These results indicate that GhERF4 may play an important
      role in response to ethylene, ABA and environmental stresses.

PMID- 18035550
TI  - In vitro study on the binding of herbicide glyphosate to human serum albumin by
      optical spectroscopy and molecular modeling.
AB  - In this study, the interaction mechanism of herbicide glyphosate and human serum
      albumin (HSA) has been characterized by fluorescence, UV, Fourier transform
      infrared (FT-IR), Circular dichroism (CD) spectroscopic and molecular modeling
      methods. The structural characteristics of glyphosate and HSA were probed, and
      affinity constants were determined under different temperatures. The enthalpy
      change (DeltaH degrees ) and the entropy changes (DeltaS degrees ) were
      calculated to be -21.78kJmol(-1) and 6.38Jmol(-1)K(-1) according to the Van't
      Hoff equation. These results indicated that glyphosate binds to HSA mainly by
      hydrogen bond and hydrophobic interaction can also not be excluded, which is in
      good agreement with the results from modeling experiment. The average binding
      distance, r, between the donor (HSA) and the acceptor (glyphosate) was evaluated
      and found to be 2.89nm according to the Forster's theory of non-radiation energy
      transfer. The alterations of protein secondary structure in the presence of
      glyphosate were confirmed by the evidences from UV, FT-IR and CD spectroscopes.

PMID- 18035551
TI  - Apoptosis in normal and cancer stem cells.
AB  - Cancer stem cells, previously identified in acute leukemias, have now been
      isolated from several human malignancies, such as breast, brain and
      gastrointestinal tumors. The origin of these cells is still questionable, but a
      growing body of evidence supports the idea that they are responsible for tumor
      growth and maintenance. For this reason, they have become a primary subject of
      investigation with a view to developing novel therapies that might lead to the
      eradication of neoplastic diseases. As previously demonstrated, cancer stem cells
      in haematological diseases have biological properties similar to those of normal
      adult stem cells. Therefore, better knowledge of the apoptotic machinery in stem
      cells might help in the development of targeted therapy for treating cancers. In
      this review, we discuss some concepts relating to stem cell biology, focusing on
      the apoptotic responses of haematopoietic and neural stem cells to conventional
      and novel cancer treatment strategies.

PMID- 18035552
TI  - Lymphoid tissue engineering: invoking lymphoid tissue neogenesis in immunotherapy
      and models of immunity.
AB  - The plasticity of the immune system is evident in the reorganization of secondary
      lymphoid organs during immune responses, lymphoid tissue neogenesis occurring
      during chronic inflammation or graft rejection, and the engineered lymphoid
      tissue formation induced by ectopic expression of single lymphoid tissue
      associated genes. Approaches seeking to harness this plasticity for immunotherapy
      are under investigation, particularly by controlling immune cell recruitment and
      lymphoid tissue formation at tumor sites. By combining strategies from ectopic
      tissue induction models with methods from tissue engineering, new approaches for
      studying lymphoid tissue development and immunotherapy may be possible.

PMID- 18035555
TI  - The GTP-binding protein Rhes modulates dopamine signalling in striatal medium
      spiny neurons.
AB  - Rhes is a small GTP-binding protein prominently localized in the striatum.
      Previous findings obtained in cell culture systems demonstrated an involvement of
      Rhes in cAMP/PKA signalling pathway, at a level proximal to the activation of
      heterotrimeric G-protein complex. However, its role in the striatum has been, so
      far, only supposed. Here we studied the involvement of Rhes in dopaminergic
      signalling, by employing mice with a null mutation in the Rhes gene. We
      demonstrated that the absence of Rhes modulates cAMP/PKA signalling in both
      striatopallidal and striatonigral projection neurons by increasing Golf protein
      levels and, in turn, influencing motor responses challenged by dopaminergic
      agonist/antagonist. Interestingly, we also show that Rhes is required for a
      correct dopamine-mediated GTP binding, a function mainly associated to
      stimulation of dopamine D2 receptors. Altogether, our results indicate that Rhes
      is an important modulator of dopaminergic transmission in the striatum.

PMID- 18035553
TI  - Human T cell reconstitution in DiGeorge syndrome and HIV-1 infection.
AB  - The thymus is essential for proper development and maintenance of a broad T cell
      repertoire capable of recognizing a wide-range of foreign antigens. Recent
      advances in multicolor flow cytometry, non-invasive imaging techniques, and
      molecular assessments of thymic function have enabled a more comprehensive
      characterization of human thymic output in clinical settings than in the past.
      These techniques have been particularly valuable in monitoring human T cells
      after therapeutic thymic grafting for complete DiGeorge syndrome and during HIV-1
      infection and AIDS. By defining the degree and mechanisms of T cell
      reconstitution in these settings, clinical investigators and primary caregivers
      have been able to better diagnose, treat and care for individuals with congenital
      or acquired immune deficiencies associated with loss of thymic function.

PMID- 18035554
TI  - Th17 cells: effector T cells with inflammatory properties.
AB  - Upon activation, naive CD4(+) T cells differentiate into effector T cells with
      specific effector functions and cytokine profiles. The Th1/Th2 paradigm has
      recently been reevaluated to include a third population of T helper cells,
      producing IL-17 and designated Th17. The differentiation of Th17 cells requires
      the coordinate and specific action of the proinflammatory cytokine IL-6 and the
      immunosuppressive cytokine TGF-beta. In addition, the IL-12 family member IL-23
      is involved in the maintenance of these cells. Analogous to other T helper cell
      subsets, Th17 commitment is initiated by sequential involvement of STAT
      molecules, i.e. STAT3 downstream of cytokine receptors, and specific
      transcription factors, i.e. ROR-gammat. Recent data also support the existence of
      a complex network of cytokines regulating Th17 cells. Clearly, the specific
      effector functions of Th17 cells expand beyond previously described effects of
      Th1 and Th2 immunity, with specific roles in host defense against certain
      pathogens and in organ-specific autoimmunity. The potential dynamics of Th17 cell
      populations and their interplay with other inflammatory cells in the induction of
      tissue inflammation in host defense and organ-specific autoimmunity are
      discussed.

PMID- 18035556
TI  - The relationship between strength, power and ballistic performance.
AB  - The purpose of this investigation was to answer the question, "Does Stronger Mean
      Faster?". After a screening for elbow strength and speed, four groups of 8
      subjects were selected for further investigation that fell into the extreme
      quartiles of the strength and speed continuums. The main investigation employed
      an apparatus that could freely rotate in the sagittal plane. Three isometric
      trials were performed at 60 degrees , 90 degrees and 120 degrees of elbow
      extension. Dynamic trials were performed with relative resistances (0, 20, 40, 60
      and 80%), determined from the lowest maximum isometric torque produced from the
      three joint angles mentioned above, and absolute resistances of 1.1 kg and 2.2
      kg. A 1:1 relationship between strength and speed was not established (r=0.498).
      Normalized peak power proved to be the best kinetic variable for predicting peak
      velocity (r ranging between 0.793 and 0.918). Individuals with similar peak
      torques were compared and the patterns of torque development, whether torques
      peaked early or late during the movement, physiologically agreed with known
      theoretically established mechanical responses. Similar velocities were also
      achieved with different peak torques demonstrating a timing issue. Estimated
      fibre-typing could not account for the performance differences.

PMID- 18035558
TI  - [11C]PIB binding in Parkinson's disease dementia.
AB  - [(11)C]PIB ((11)C-6-OH benzothiazole) reflects the regional distribution of
      amyloid (beta-sheeted proteins) in patients with Alzheimer's disease (AD).
      Proteinaceous inclusions in Parkinson's disease with dementia (PDD), so-called
      Lewy bodies, also consist of fibrillar, misfolded proteins, chiefly alpha
      synuclein. To test whether PDD subjects show specific amyloid binding in vivo and
      whether this could reflect fibrillar alpha-synuclein accumulation, we
      investigated 10 PDD subjects with [(11)C]PIB-PET. Radioligand binding was
      compared to that in 11 control and 6 AD subjects. Furthermore, postmortem
      sections of 4 patients with Parkinson's disease (PD), therefrom 2 with dementia
      (PDD), and of 6 controls were stained with PIB to evaluate the histological
      distribution of the fluorescent ligand in the brainstem. In PET, only 2 PDD
      patients displayed increased PIB binding to cortical amyloid comparable to AD
      patients. The other 8 patients showed control-like cortical findings but elevated
      PIB binding in the pons and mesencephalon. Fluorescence microscopy showed PIB
      binding to Lewy bodies and neuromelanin in the substantia nigra of PD and PDD
      brainstem sections, but not in controls. These data suggest that PIB-PET can be
      used to further differentiate PDD with respect to cortical amyloid. Furthermore,
      we provide evidence that--in addition to nonspecific binding--PIB uptake in the
      brainstem may also reflect PDD related amyloid.

PMID- 18035557
TI  - Neural mechanisms underlying auditory feedback control of speech.
AB  - The neural substrates underlying auditory feedback control of speech were
      investigated using a combination of functional magnetic resonance imaging (fMRI)
      and computational modeling. Neural responses were measured while subjects spoke
      monosyllabic words under two conditions: (i) normal auditory feedback of their
      speech and (ii) auditory feedback in which the first formant frequency of their
      speech was unexpectedly shifted in real time. Acoustic measurements showed
      compensation to the shift within approximately 136 ms of onset. Neuroimaging
      revealed increased activity in bilateral superior temporal cortex during shifted
      feedback, indicative of neurons coding mismatches between expected and actual
      auditory signals, as well as right prefrontal and Rolandic cortical activity.
      Structural equation modeling revealed increased influence of bilateral auditory
      cortical areas on right frontal areas during shifted speech, indicating that
      projections from auditory error cells in posterior superior temporal cortex to
      motor correction cells in right frontal cortex mediate auditory feedback control
      of speech.

PMID- 18035560
TI  - Rapid screening of 10 common mutations in Turkish Gaucher patients using
      electronic DNA microarray.

PMID- 18035561
TI  - Coordinating cell proliferation and migration in the lens and cornea.
AB  - Migration is a complex process for epithelial tissues, because the epithelium
      must move as an intact sheet to preserve its barrier function. The requirement
      for structural integrity is met by coupling cell-to-matrix and cell-to-cell
      adhesion at the cellular level, and by coordinating cell proliferation and cell
      migration in the tissue as a whole. Proliferation is suppressed at the migrating
      cell front, allowing cells in this region to remain tightly packed while
      advancing rapidly. At the same time, proliferation is enhanced in a region behind
      the advancing cell front to expand the epithelial cell sheet. This review
      considers the extracellular signals and intracellular signaling pathways that
      regulate these processes in the lens and corneal epithelium, with emphasis on the
      commonalities that link these tissues.

PMID- 18035562
TI  - Eye evolution: lens and cornea as an upgrade of animal visual system.
AB  - Lens-containing eyes are a feature of surprisingly broad spectrum of organisms
      across the animal kingdom that represent a significant improvement of simple eye
      composed of just photoreceptor cells and pigment cells. It is apparent that such
      an upgrade of animal visual system has originated numerous times during evolution
      since many distinct strategies to enhance light refraction through the use of
      lens and cornea have been utilized. In addition to having an ancient role in
      prototypical eye formation Pax transcription factors were convergently recruited
      for regulation of structurally diverse crystallins and genes affecting
      morphogenesis of various lens-containing eyes.

PMID- 18035563
TI  - Uterine receptivity to human embryonic implantation: histology, biomarkers, and
      transcriptomics.
AB  - Embryonic implantation is a dynamic process of paracrine interactions between the
      maternal compartment and the conceptus and involves a receptive endometrium and a
      developmentally competent blastocyst. Herein, we review histology, clinical
      approaches, and the promise of transcriptomics in elucidating mechanisms
      underlying implantation and development of biomarkers of uterine receptivity-with
      an eye to diagnose and treat implantation-based disorders of miscarriage, fetal
      growth restriction, pre-eclampsia, and infertility.

PMID- 18035565
TI  - An adaptive evolutionary shift in Fusarium head blight pathogen populations is
      driving the rapid spread of more toxigenic Fusarium graminearum in North America.
AB  - Analysis of Fusarium head blight (FHB) pathogen diversity revealed that 3ADON
      producing Fusarium graminearum are prevalent in North America and identified
      significant population structure associated with trichothecene chemotype
      differences (F(ST)>0.285; P<0.001). In addition, we identified a trichothecene
      chemotype cline in Canada and documented a recent and significant shift in FHB
      pathogen composition by demonstrating that the 3ADON chemotype frequency in
      western Canada increased more than 14-fold between 1998 and 2004. On average,
      isolates from 3ADON populations produced significantly (P<0.05) more
      trichothecene and had significantly (P<0.005) higher fecundity and growth rates
      than isolates from the 15ADON population. These results indicate that selection
      is driving the rapid spread of an introduced pathogen population that is more
      toxigenic and potentially more vigorous. The discovery of this previously
      unrecognized pathogen diversity has significant implications for food safety and
      cereal production in North America.

PMID- 18035566
TI  - The effect of electroacupuncture on opioid-like medication consumption by chronic
      pain patients: a pilot randomized controlled clinical trial.
AB  - Opioid-like medications (OLM) are commonly used by patients with various types of
      chronic pain, but their long-term benefit is questionable. Electroacupuncture
      (EA) has been previously shown beneficial in reducing post-operative acute OLM
      consumption. In this pilot randomized controlled trial, the effect of EA on OLM
      usage and associated side effects in chronic pain patients was evaluated. After a
      two-week baseline assessment, participants using OLM for their non-malignant
      chronic pain were randomly assigned to receive either real EA (REA, n=17) or sham
      EA (SEA, n=18) treatment twice weekly for 6 weeks before entering a 12-week
      follow-up. Pain, OLM consumption and their side effects were recorded daily.
      Participants also completed the McGill Pain Questionnaire (MPQ), SF-36 and Beck
      Depression Inventory (BDI) at baseline, and at the 5th, 8th, 12th, 16th and 20th
      week. Nine participants withdrew during the treatment period with another three
      during the follow-up period. Intention to treat analysis was applied. At the end
      of treatment period, reductions of OLM consumption in REA and SEA were 39% and
      25%, respectively (p=0.056), but this effect did not last more than 8 weeks after
      treatment. There was no difference between the two groups with respect to
      reduction of side effects and pain and the improvement of depression and quality
      of life. In conclusion, REA demonstrates promising short-term reduction of OLM
      for participants with chronic non-malignant pain, but such effect needs to be
      confirmed by trials with adequate sample sizes.

PMID- 18035567
TI  - 5- and 6-pulse electron spin echo envelope modulation (ESEEM) of multi-nuclear
      spin systems.
AB  - In 3-pulse ESEEM and the original 4-pulse HYSCORE, nuclei with large modulation
      depth (k approximately 1) suppress spectral peaks from nuclei with weak
      modulations (k approximately 0). This cross suppression can impede the detection
      of the latter nuclei, which are often the ones of interest. We show that two
      extended pulse sequences, 5-pulse ESEEM and 6-pulse HYSCORE, can be used as
      experimental alternatives that suffer less strongly from the cross suppression
      and allow to recover signals of k approximately 0 nuclei in the presence of k
      approximately 1 nuclei. In the extended sequences, modulations from k
      approximately 0 nuclei are strongly enhanced. In addition, multi-quantum
      transitions are absent which simplifies the spectra. General analytical
      expressions for the modulation signals in these sequences are derived and
      discussed. Numerical simulations and experimental spectra that demonstrate the
      higher sensitivity of the extended pulse sequences are presented.

PMID- 18035564
TI  - Congenital cataracts and their molecular genetics.
AB  - Cataract can be defined as any opacity of the crystalline lens. Congenital
      cataract is particularly serious because it has the potential for inhibiting
      visual development, resulting in permanent blindness. Inherited cataracts
      represent a major contribution to congenital cataracts, especially in developed
      countries. While cataract represents a common end stage of mutations in a
      potentially large number of genes acting through varied mechanisms in practice
      most inherited cataracts have been associated with a subgroup of genes encoding
      proteins of particular importance for the maintenance of lens transparency and
      homeostasis. The increasing availability of more detailed information about these
      proteins and their functions and is making it possible to understand the
      pathophysiology of cataracts and the biology of the lens in general.

PMID- 18035568
TI  - Carotenoids and throat pouch coloration in the great frigatebird (Fregata minor).
AB  - Carotenoid pigments are a common source of red, orange, and yellow coloration in
      vertebrates. Animals cannot manufacture carotenoids and therefore must obtain
      them in their diet to produce carotenoid-based coloration. Male great
      frigatebirds (Fregata minor) display a bright red inflated gular pouch as part of
      their elaborate courtship display. The basis of this coloration until now has not
      been investigated. Using high-performance liquid chromatography (HPLC), we
      investigated the types and concentrations of carotenoids that great frigatebirds
      circulate in their plasma and whether male gular pouch coloration was carotenoid
      based. Great frigatebird plasma collected during the breeding season contained
      three carotenoid pigments in dilute concentrations-tunaxanthin, zeaxanthin, and
      astaxanthin-with astaxanthin accounting for nearly 85% of the carotenoids
      present. Astaxanthin was the only carotenoid present in gular pouch tissue, but
      the concentration is the highest reported for any carotenoid-pigmented avian
      tissue. Throat pouch reflectance curves were measured with a UV-VIS
      spectrophotometer, revealing a complex pattern of one UV peak (approx. 360 nm),
      two absorption valleys (approx. 542 and 577 nm), followed by a plateau at approx
      630 nm. The reflectance curve suggests a role for additional pigments, in
      particular hemoglobin, in the production of color in this ornament.

PMID- 18035570
TI  - Increasing penicillin and trimethoprim-sulfamethoxazole resistance in
      nasopharyngeal Streptococcus pneumoniae isolates from Guatemalan children, 2001-
      2006.
AB  - OBJECTIVES: We aimed to determine nasopharyngeal colonization rates and
      antibiotic resistance patterns of Streptococcus pneumoniae isolated from
      Guatemalan children, and to determine risk factors for colonization and
      antibiotic nonsusceptibility. METHODS: Isolates were obtained from children aged
      5 to 60 months attending public and private outpatient clinics and daycare
      centers during August 2001--June 2002 and outpatient clinics during November 2005
      -February 2006 in Guatemala City. Minimal inhibitory concentrations of
      penicillin, trimethoprim-sulfamethoxazole (TMS), cefotaxime, and erythromycin
      were determined using the E-test. RESULTS: The overall nasopharyngeal
      colonization rate for S. pneumoniae was 59.1%. From 2001/2 to 2005/6 TMS
      nonsusceptibility increased from 42.4% to 60.8% (p<0.05) in public clinics and
      from 51.4% to 84.0% (p=0.009) in private clinics, and penicillin
      nonsusceptibility increased from 1.5% to 33.3% in public clinics (p<0.001).
      Reported antibiotic use was not strictly associated with nonsusceptibility to
      that same antibiotic. Resistance to three or four antibiotics increased in public
      clinics from 2001/2 (0%) to 2005/6 (10.7%; p<0.001). Risk factors for
      nasopharyngeal colonization with penicillin- or TMS-nonsusceptible S. pneumoniae
      were low family income, daycare center attendance, and recent penicillin use.
      CONCLUSIONS: Increasing antibiotic nonsusceptibility rates in nasopharyngeal S.
      pneumoniae isolates from Guatemalan children reflect worldwide trends. Policies
      encouraging more judicious use of TMS should be considered.

PMID- 18035571
TI  - [Management of high risk pregnancy in sickle cell disease by a strategy of
      prophylactic red cell transfusion or automated red cell exchange].
AB  - OBJECTIVE: Maternal and fetal risk is often high during pregnancy in sickle cell
      disease. Our objective was to evaluate the benefits of a transfusion program
      adapted to each pregnant patient, either by red cell transfusion or by automated
      red cell exchange, in sickle cell patients with a history of serious obstetrical
      and/or sickling complications. STUDY DESIGN: We managed 18 pregnancies in 14
      patients (12 SS, 1 SC, 1 S/b-thalassemia), seven of whom had a history of one or
      more pregnancies, with severe maternofetal complications in nine out of 10 cases.
      The other seven patients were pregnant for the first time and were in care
      because of a history of severe sickling complications. The aim was to achieve a
      proportion of abnormal hemoglobin (hemoglobin S or S+C) below 50% and a
      hemoglobin level between 9 and 11 g/dL. The choice between transfusion and red
      cell exchange was made in the light of the hemoglobin level. Red cell exchange
      was done using a Fresenius Com. Tec blood cell separator. Patients had red cell
      exchange in 10 cases, and transfusions in five cases. In three cases, patients
      had successive transfusions and red cell exchange. RESULTS: No serious maternal
      complication was observed. No fetal or perinatal death occurred. In one case,
      delivery was induced at 36 weeks of gestation because of fetal distress and
      hypotrophy. CONCLUSIONS: Our study suggests that women with severe sickle cell
      disease, even if they have a serious obstetrical history, can carry their
      pregnancy to term, without major obstetric complications, through a combination
      of early management by a multidisciplinary team and a suitable policy of
      prophylactic transfusion or automated red cell exchange.

PMID- 18035569
TI  - Sphingolipids and membrane biology as determined from genetic models.
AB  - The importance of sphingolipids in membrane biology was appreciated early in the
      twentieth century when several human inborn errors of metabolism were linked to
      defects in sphingolipid degradation. The past two decades have seen an explosion
      of information linking sphingolipids with cellular processes. Studies have
      unraveled mechanistic details of the sphingolipid metabolic pathways, and these
      findings are being exploited in the development of novel therapies, some now in
      clinical trials. Pioneering work in yeast has laid the foundation for identifying
      genes encoding the enzymes of the pathways. The advent of the era of genomics and
      bioinformatics has led to the identification of homologous genes in other species
      and the subsequent creation of animal knock-out lines for these genes.
      Discoveries from these efforts have re-kindled interest in the role of
      sphingolipids in membrane biology. This review highlights some of the recent
      advances in understanding sphingolipids' roles in membrane biology as determined
      from genetic models.

PMID- 18035572
TI  - Alteration in sympathoadrenergic activity at rest and during intense exercise
      despite normal aerobic fitness in late pubertal adolescent girls with type 1
      diabetes.
AB  - BACKGROUND: An impaired sympathoadrenergic response to hypoglycaemic episodes has
      been described in young Type 1 diabetic subjects. It is unknown if this altered
      response occurs with exercise, and if it could influence aerobic power. METHODS:
      Body composition (skinfold thickness), physical activity (questionnaire) and
      aerobic power (PWC170 and VO2max) were assessed in 19 post-menarcheal Type 1
      diabetic (T1D) girls (13.3-18.2 years) and 19 healthy siblings. At rest and at
      each stage of the graded exhaustive exercise, plasma glucose, insulin,
      epinephrine and norepinephrine, were monitored via an intravenous catheter.
      RESULTS: Only when expressed per kilograms of body weight, was aerobic power
      impaired in T1D girls compared to controls, probably because they were
      overweight. Throughout exercise, plasma glucose remained stable while plasma
      insulin decreased in the healthy girls, whereas glucose diminished significantly
      with no change in plasma insulin in T1D girls. During exercise catecholamines
      increased in the same way in both groups. However, at rest and throughout all
      stages of exercise, norepinephrine levels were significantly lower by a mean
      difference of 1.2 nmol/L, while epinephrine levels were significantly higher by a
      mean difference of 0.14 nmol/L, in T1D girls compared to healthy girls. Heart
      rates of T1D girls were not affected by the sympathoadrenergic alteration.
      CONCLUSION: T1D adolescent girls display an altered sympathoadrenergic activity
      at rest and during intense exercise. Their reduced sympathetic activity, albeit
      probably compensated for by higher adrenomedullary responsiveness or sensitivity,
      does not affect their heart rate adaptations to exercise.

PMID- 18035573
TI  - Role of the mitogen-activated protein kinase pathway in the differential response
      of bovine monocytes to Mycobacterium avium subsp. paratuberculosis and
      Mycobacterium avium subsp. avium.
AB  - We compared the kinetics of activation and antimicrobial activities of MAPK-p38
      and MAPK-ERK in bovine monocytes infected with Mycobacterium avium subsp.
      paratuberculosis (MAP) and Mycobacterium avium subsp. avium (Maa). Monocytes were
      incubated with MAP or Maa organisms with or without a specific inhibitor of the
      MAPK-p38 pathway (SB203580), and MAPK phosphorylation and antimicrobial functions
      of monocytes were evaluated. At early time points MAPK-p38 phosphorylation was
      greater in MAP-infected bovine monocytes than in Maa-infected monocytes. At later
      time points MAPK-p38 phosphorylation by both organisms was similar. MAPKp38
      phosphorylation in MAP-infected monocytes was similar to negative control cells,
      whereas in Maa-infected this activation remained greater than negative control
      cells. Increase phosphorylation MAPK-ERK was similar at all time points for both
      organisms. Bovine monocytes had minimal capacity to kill MAP organisms, to
      acidify MAP-containing phagosomes, or to form phagolysosome. Alternatively,
      bovine monocytes were able to kill Maa organisms. Addition of SB203580 to
      monocyte cultures increased phagosome acidification, phagolysosome formation, and
      killing of MAP and Maa organisms. Taken together these data indicate that early
      transient activation of MAPK-p38 in bovine mononuclear phagocytes by MAP
      organisms may be a key mechanism involved in the capacity of MAP to survive in
      bovine monocytes.

PMID- 18035574
TI  - [Being pregnant over 45 after oocyte donation in a foreign country. A wonder of
      medicine or an ethical transgression?].
AB  - The French legislation strictly controls the organization of assisted
      reproductive techniques (ART). The menopaused women are not allowed access to
      this kind of medical care. For women who still want to be pregnant, oocyte
      donation in a foreign country may offer a solution. The mortality and morbidity
      rates are higher for these women compared to the general population. We report
      two cases of pregnancy after oocyte donation in women around 45 years of age. The
      first one was complicated by preeclampsia and gestational diabetes. The second
      patient suffered from severe postpartum complications that needed intensive care
      during three weeks. The clinical consequences are discussed, together with
      legislative and ethical issues.

PMID- 18035575
TI  - [Ethical issues of preimplantation diagnosis].

PMID- 18035576
TI  - [Reply to M.-V. Senat and R Frydman about their article: Increased nuchal
      translucency with normal karyotype Gynecol Obstet Fertil 2007;35:507-15].

PMID- 18035577
TI  - [Role of defecography in female posterior pelvic floor abnormalities].
AB  - Pelvic floor abnormalities often impact significantly the quality of life and
      result in a variety of symptoms, including chronic pelvic pain, fecal
      incontinence, and obstructed constipation. Fluoroscopic defecography and MR
      defecography enable identification of rectocele, rectal prolapse, enterocele,
      sigmoidocele with high prevalence in female patients with obstructed
      constipation, fecal incontinence, and chronic pelvic pain. In this manuscript, we
      describe the techniques and indications of the two techniques of defecography. We
      discuss the abnormalities of the posterior pelvic floor compartment at the origin
      of constipation, incontinence, chronic pelvic pain. Finally we compare the data
      obtained by clinical examination and defecography, remembering that 50% of
      enterocele and 100% of sigmoidocele are missed at clinical examination.

PMID- 18035578
TI  - [How I perform...the preventive occlusion of the uterine arteries before
      myomectomy or hysterectomy?].

PMID- 18035579
TI  - [The male genital tract: A host for HIV].
AB  - Despite semen being the main vector of human immunodeficiency virus (HIV)
      dissemination worldwide, the origin of the virus in this bodily fluid remains
      unknown. Of particular significance is the persistence of virus release in the
      semen of HIV-infected men under antiretroviral therapy, who otherwise show an
      undetectable blood viral load. It is therefore considered critical to identify
      the sources of virus shedding in semen for the more efficient control of HIV
      transmission. A number of studies indirectly suggest that the free viral
      particles and infected cells contaminating semen are produced within the male
      genital tract. Our recent findings indicate HIV infection of several semen
      producing organs, including the testis (which represents a pharmacological
      sanctuary for several antiretroviral drugs), thus reinforcing the hypothesis of
      the local origin of the seminal contamination. Whether one or several of these
      organs constitute a viral reservoir seeding semen despite antiviral therapies,
      remains to be determined. In addition, the detection of virus within the
      testicular germ cells should be taken into account in the context of assisted
      reproductive techniques using these cells from HIV positive men.

PMID- 18035580
TI  - [Digestive endometriosis of the caecum and intussusception: about one case].
AB  - We report the case of a 40-years-old woman who had a caeco-colic intussusception
      on a digestive endometriosis. Such exceptional association can be life
      threatening, requiring urgent surgery.

PMID- 18035581
TI  - [Uterine abnormalities in non menopausal women who received tamoxifen for breast
      cancer adjuvant therapy].
AB  - OBJECTIVE: To elaborate a strategy of endometrial follow-up for premenopausal
      women treated with Tamoxifen as adjuvant hormonal treatment of breast cancer.
      PATIENTS AND METHODS: Retrospective study of 152 premenopausal patients treated
      with Tamoxifen in Nantes Comprehensive Cancer Center for a breast cancer from
      January 2003 to December 2005. Vaginal sonography was used in the follow-up of 70
      of them. RESULTS: Endometrial hypertrophy was found in 26 patients.
      Sonohysterography and hysteroscopy allowed to find 11 polyps and three
      hyperplasias in the 19 women who were investigated. In our study, endometrial
      pathology was found in 20% of premenopausal women treated with Tamoxifen (polyps
      or hyperplasia). Uterine bleeding was found in half patient of this group.
      DISCUSSION AND CONCLUSION: Vaginal sonography monitoring could be proposed to
      premenopausal women treated with Tamoxifen among whom endometrial pathology is
      usual.

PMID- 18035582
TI  - The impact of DNA contamination of bone samples in forensic case analysis and
      anthropological research.
AB  - Contamination precautions and quality control are great issues when human bones
      are investigated genetically. This is especially true for historical samples with
      only minute amounts of usually highly degraded DNA. But also in forensic routine
      analysis, sometimes DNA has to be isolated from bones in equally bad conditions,
      e.g. from burned victims. In such cases, there are several eventualities to
      contaminate the sample with foreign DNA, for example caused by the recovery of
      the bones, by trace investigation on a crime scene, or - of course - during
      handling in the lab. We present the investigation of artificially contaminated
      historical bone samples which contained no original DNA. Three different kind of
      contamination were studied: (1) touching of the samples, (2) application of
      saliva, and (3) application of pure DNA. The samples were genetically
      investigated without and with the employment of a defined cleaning protocol of
      the bones. The results show that pure DNA can usually not be removed from the
      bones and that saliva is a similar thread for subsequent DNA analysis. After the
      cleaning procedure about 70% of saliva contaminated samples still yielded
      reproducible STR profiles implicating severe problems for the investigation of
      highly degraded bone fragments. Simple touching of the specimens seems not to be
      a real problem for genetic investigations since the obtained signals were not
      reproducible.

PMID- 18035583
TI  - Postmortem diagnosis of fatal anaphylaxis during intravenous administration of
      therapeutic and diagnostic agents: evaluation of clinical laboratory parameters
      and immunohistochemistry in three cases.
AB  - This report documented three autopsy cases involving fatal shock during
      intravenous injection of therapeutic and diagnostic agents in a hospital setting.
      For postmortem diagnosis, clinical laboratory parameters for anaphylaxis,
      specificity of antibodies for allergens and mast cell numbers in tissue sections
      were examined. Elevated plasma tryptase levels were evident in the three adult
      males; two of the three victims displayed elevated IgE levels. However,
      immunoassay failed to detect antibodies specific to the relevant agent. Double
      immuno-staining was performed employing anti-tryptase and anti-chymase monoclonal
      antibodies in order to count mast cells in lung sections. Increased numbers of
      mast cells were observed in anaphylactic tissues, which was particularly true for
      chymase-positive cells, in comparison with tissues associated with acute
      traumatic deaths. In addition to findings at autopsy, positive data obtained by
      laboratory examinations and immunohistochemical analyses indicated that fatal
      systemic anaphylaxis occurred during intravenous injection of clinical agents.

PMID- 18035584
TI  - Behcet's disease: ocular effects and treatment.
AB  - Behcet's disease (BD) is a systemic immune-mediated vasculitis of unclear origin.
      Major symptoms include oral aphthous ulcers, genital ulcerations, skin lesions,
      and ocular lesions. Eye involvement, which affects 60-80% of BD patients, is
      characterized by posterior or panuveitis with occlusive retinal vasculitis. The
      pathogenesis of BD remains unclear, but research of the last decades has shown a
      complex role of genetic factors (HLA-B51) predisposing to inflammation with
      involvement of the innate-immune system (neutrophils, NK cells), perpetuated by
      the adaptive immune response, most importantly T cells, against infectious-
      and/or auto-antigens. Despite aggressive immunosuppressive treatment, the visual
      prognosis of ocular BD was generally poor to date. Recently, novel biologic
      drugs, including interferon-alpha and tumour necrosis factor (TNF)-alpha
      antagonists have been introduced in the treatment of ocular BD with very
      promising results and seem for the first time to improve the prognosis of the
      disease. This article will provide a current review of BD including recent
      developments in epidemiology, immunology, genetics, and treatment.

PMID- 18035586
TI  - Shape, polarity, and multicellular morphogenesis.

PMID- 18035585
TI  - SOCS 3 and PPAR-gamma ligands inhibit the expression of IL-6 and TGF-beta1 by
      regulating JAK2/STAT3 signaling in pancreas.
AB  - Induction of proinflammatory cytokines IL-6 and TGF-beta1 are the hallmark of
      human pancreatitis. Cerulein pancreatitis is similar to human edematous
      pancreatitis involving dysregulation of digestive enzyme production, cytoplasmic
      vacuolization, and increased cytokine production. We previously showed that
      cerulein induced IL-1beta expression through the Janus kinase (JAK) 2/signal
      transducer and activator of transcription (STAT) 3 pathway in pancreatic acinar
      cells. Suppressor of cytokine signaling (SOCS) is a negative feedback regulator
      of JAK/STAT signaling. In this study, we demonstrate that SOCS 3 is induced by
      cerulein in pancreatic acinar AR42J cells and in the rat pancreas. In both AR42J
      cells and rat pancreas, cerulein induced expression of IL-6 and TGF-beta1, which
      is enhanced by transfection or injection of SOCS 3 antisense oligonucleotide (AS
      ODN). Pre-treating cerulein-stimulated AR42J cells or rats with the peroxisome
      proliferator activated receptor-gamma (PPAR-gamma) ligands, 15d-PGJ2 and
      troglitazone, induced SOCS 3 expression and inhibited JAK2/STAT3 activation. This
      treatment regimen also inhibited IL-6 and TGF-beta1 induction, vacuolization, and
      alpha-smooth muscle actin (alpha-SMA) expression. Thus, SOCS 3 expression is
      associated with a reduction in IL-6 and TGF-beta1 expression, edema formation,
      vacuolization, and alpha-SMA expression, possibly by direct regulation of
      JAK2/STAT3 signaling. 15d-PGJ2 and troglitazone are potentially useful
      pancreatitis therapies by suppressing the JAK2/STAT3 inflammatory signaling
      through SOCS 3 induction.

PMID- 18035587
TI  - Occurrence of gastrointestinal protozoa in Didelphis albiventris (opossum) in the
      central region of Rio Grande do Sul state.
AB  - The aim of this study was to evaluate the parasitism by gastrointestinal protozoa
      in Didelphis albiventris (opossum) in the central region of Rio Grande do Sul
      state. Fecal samples from six free living opossums were collected for research of
      parasites. Samples were analyzed by the centrifugal-flotation method with zinc
      sulfate and parasites were identified microscopically based on (oo)cyst size and
      morphology. Cysts of Giardia sp. and oocysts of Cryptosporidium sp. and Eimeria
      sp. were observed in four of the six opossums. All four infected marsupials
      showed mild infection by protozoa. This is the first report of Giardia sp. in D.
      albiventris.

PMID- 18035588
TI  - Density functional theory study of vibrational spectra, and assignment of
      fundamental vibrational modes of 1-bromo 4-fluoronaphthalene.
AB  - The FTIR and FT-Raman spectra of 1-bromo 4-fluoronaphthalene have been recorded
      in the regions 4000-100 cm(-1) and 3500-100 cm(-1), respectively. The spectra
      were interpreted with the aid of normal coordinate analysis based on DFT (density
      functional theory) using standard B3LYP/6-311+G** basis set combination for the
      most optimized geometry. Normal coordinate calculations performed with the DFT
      force field and subsequently corrected by a recommended set of scale factors,
      yielded fairly good agreement between observed and calculated frequencies. On the
      basis of the comparison between calculated and experimental results, assignments
      of fundamental modes were examined.

PMID- 18035589
TI  - Health data quality improvement by comparing administrative medical data and
      billing data.
AB  - OBJECTIVE: The increasing use of medical administrative databases in hospital
      financing means more attention is being paid to their quality. The object of this
      study is to compare diagnoses found in the medical database to treatments
      mentioned in the billing database and to identify hospital stays with
      discrepancies. METHOD: The analysis is performed for the diagnoses of heart
      failure, hypertension, and pneumonia. Data were extracted from the 2000 National
      Medical Minimum Basic Data Set (MBDS) database and from the 2000 National bill
      summary database. The in-hospital stays were split into four analysis groups:
      patients with the selected disease and a corresponding treatment, patients with
      the selected disease but without a corresponding treatment, patients with a
      treatment, without the selected disease, but with another pathology requiring the
      same treatment, and patients with a treatment, without the selected disease and
      without any other pathology requiring the same treatment. RESULTS: The proportion
      of in-hospital stays with the disease in the medical database but without a
      corresponding treatment mentioned in the billing database was 1.1% for heart
      failure, 12.0% for hypertension, and 5.1% for pneumonia. Under-reporting (patient
      with a treatment but without any corresponding disease) concerned a high
      proportion of stays for heart failure and for hypertension (29.6% and 26.8%,
      respectively). CONCLUSIONS: This database comparison identified hospital stays
      with discrepancies between the medical database and the billing database. This
      method allows a better focus on the medical MBDS to be reviewed but must be
      completed by a thorough analysis of the medical chart. An extension of this
      methodology to other pathology would be useful to assess the quality of
      administrative data.

PMID- 18035590
TI  - Chronic subdural electrodes in the management of epilepsy.
AB  - Subdural electrodes play a very important role in the evaluation of a percentage
      of patients being considered for epilepsy surgery. Electrical activity at very
      low and very high frequencies, beyond the practical range of scalp EEG, can be
      recorded subdurally and may contain considerable information not available non
      invasively. The recording and stimulating procedures for using chronically
      implanted subdural electrodes to localize the epileptogenic zone and map eloquent
      functions of the human cortex are well established, and complication rates are
      low. Complications include infections, CSF leak, and focal neurologic deficits,
      all of which tend to be increased with a higher number of electrodes and longer
      duration of recordings. Careful consideration of the risks and benefits should be
      coupled with a firm hypothesis about the epileptogenic zone derived from the non
      invasive components of the epilepsy workup to guide the decision about whether
      and where to implant subdural electrodes. When they are employed to answer a
      specific question in an individual patient, subdural electrodes can optimize the
      clinical outcome of a candidate for epilepsy surgery.

PMID- 18035591
TI  - The pain-induced decrease in low-threshold motor unit discharge rate is not
      associated with the amount of increase in spike-triggered average torque.
AB  - OBJECTIVE: Activation of nociceptive afferents decreases motor unit discharge
      rates in static contractions. There is also evidence that during experimental
      muscle pain the motor unit twitch force increases, which has been hypothesized to
      compensate for the decrease in discharge rate to maintain constant force. This
      study examined whether there is an association between the magnitude of change in
      motor unit discharge rate and the amount of increase in the spike-triggered
      average torque during experimental muscle pain. METHODS: Sixteen subjects
      performed three constant-torque isometric ankle dorsi-flexions at 10% of the
      maximal force (MVC) alternated with two contractions at constant discharge rate
      of a target motor unit, before and following injection of 0.5 ml of hypertonic
      (painful) or isotonic (control) saline into the tibialis anterior muscle.
      RESULTS: The discharge rate of the target unit at 10% MVC decreased following
      injection of hypertonic saline (P<0.05; mean+/-SD, before: 9.9+/-1.3 pulses per
      second, pps; after injection: 8.9+/-1.0 pps). The peak of the spike-triggered
      average torque increased with pain (P<0.05; before: 0.56+/-0.55 mNm; during pain:
      0.95+/-1.02 mNm) but the increase was not correlated with the decrease in
      discharge rate (R=0.08). Propagation velocity and action potential peak-to-peak
      amplitude did not change with pain. CONCLUSIONS: The pain-induced modifications
      in the estimated motor unit twitch torque (1) were not caused by changes in
      muscle fiber action potential, and (2) were not associated with the decrease in
      discharge rate. SIGNIFICANCE: Maintenance of constant force during static painful
      contractions is not explained by a matching between changes in contractile and
      control motor unit properties.

PMID- 18035592
TI  - Fetal stem-cell transplantation.
AB  - Fetal stem-cell transplantation is an attractive approach to the treatment of a
      variety of hematological, metabolic and immunological diseases before birth. The
      possibility of delivering a large number of cells in an early stage of life, and
      of taking advantage of normal fetal stem-cell migration and development, is
      promising. During fetal life, the capacity to mount an immune response to
      allogeneic cells is impaired compared with adult life. This provides an
      opportunity to induce tolerance to alloantigens without the need for
      myeloablation, although there are possible immune barriers to foreign cells in
      the fetus.

PMID- 18035593
TI  - Epilepsy surgery after age 60.
AB  - Data from seven patients 60 years of age and older who underwent temporal
      lobectomy were reviewed. Outcome was comparable to younger patients. Despite the
      small number of patients and retrospective nature of the study, the data support
      the efficacy and safety of temporal lobectomy in this age group.

PMID- 18035594
TI  - An analytical method for size and shape characterization of blood lipoproteins.

PMID- 18035595
TI  - Lanthanide phosphate nanorods as inorganic fluorescent labels in cell biology
      research.

PMID- 18035596
TI  - Development of a novel, rapid, and sensitive immunochromatographic strip assay
      specific for West Nile Virus (WNV) IgM and testing of its diagnostic accuracy in
      patients suspected of WNV infection.

PMID- 18035597
TI  - The LiMA technology: measurement of ATP on a nucleic acid testing platform.

PMID- 18035598
TI  - Homoeopathy booming in India.

PMID- 18035599
TI  - Malfunction of an adjustable pressure limit valve.

PMID- 18035600
TI  - ProSeal LMA: a potentially dangerous modification.

PMID- 18035601
TI  - Spinal anaesthesia for emergency Caesarean section in an achondroplastic patient.

PMID- 18035602
TI  - Partial airway obstruction caused by dissection of a reinforced endotracheal
      tube.

PMID- 18035603
TI  - Changes in renal function in valvular and coronary patients.

PMID- 18035604
TI  - Effect of dexmedetomidine on blood pressure and bleeding in maxillo-facial
      surgery.

PMID- 18035605
TI  - Bringing biomarkers to the masses: an elegant approach to discover potential
      biomarkers of vascular injury.

PMID- 18035606
TI  - The mechanism of isoniazid killing: clarity through the scope of genetics.
AB  - Isoniazid (INH) is one of the most efficient drugs for the treatment of
      Mycobacterium tuberculosis infections. Despite its rather simple chemical
      structure, the mechanism by which INH kills M. tuberculosis is complex. A full
      understanding of the mechanisms of action of INH required the development of
      genetic tools in M. tuberculosis. Herein, we discuss the different hypotheses
      that have been used to describe INH action against M. tuberculosis over the past
      50 years in terms of the pregenetic and genetic era. We also review the different
      mechanisms of INH resistance and propose what we think is the means by which INH
      kills M. tuberculosis.

PMID- 18035607
TI  - SigB-dependent general stress response in Bacillus subtilis and related gram
      positive bacteria.
AB  - One of the strongest and most noticeable responses of Bacillus subtilis cells to
      a range of stress and starvation stimuli is the dramatic induction of about 150
      SigB-dependent general stress genes. The activity of SigB itself is tightly
      regulated by a complex signal transduction cascade with at least three main
      signaling pathways that respond to environmental stress, energy depletion, or low
      temperature. The SigB-dependent response is conserved in related gram-positive
      bacteria but is missing in strictly anaerobic or in some facultatively anaerobic
      gram-positive bacteria. It covers functions from nonspecific and multiple stress
      resistance to the control of virulence in pathogenic bacteria. A comprehensive
      understanding of this crucial stress response is essential not only for bacterial
      physiology but also for applied microbiology, including pathogenicity and
      pathogen control.

PMID- 18035608
TI  - Ecology and biotechnology of the genus Shewanella.
AB  - The shewanellae are aquatic microorganisms with worldwide distribution. Their
      hallmark features include unparalleled respiratory diversity and the capacity to
      thrive at low temperatures. As a genus the shewanellae are physiologically
      diverse, and this review provides an overview of the varied roles they serve in
      the environment and describes what is known about how they might survive in such
      extreme and harsh environments. In light of their fascinating physiology, these
      organisms have several biotechnological uses, from bioremediation of chlorinated
      compounds, radionuclides, and other environmental pollutants to energy-generating
      biocatalysis. The ecology and biotechnology of these organisms are intertwined,
      with genomics playing a key role in our understanding of their physiology.

PMID- 18035609
TI  - Microbial metabolism of reduced phosphorus compounds.
AB  - The field of bacterial phosphorus (P) metabolism has undergone a significant
      transformation in the past decade owing to the elucidation of widespread and
      diverse pathways for the metabolism of reduced P compounds. The characterization
      of these pathways dramatically changes the current and narrow view of P
      metabolism and our understanding of the forms in which P is produced and
      available in the environment. In this review, recent investigations into the
      biochemical pathways and molecular genetics of reduced P metabolism in bacteria
      are discussed. Particular attention is paid to recently elucidated metabolic
      reactions and the genetic characterization of biosynthesis of organic reduced P
      compounds and to the pathways for oxidation of the inorganic reduced P compounds
      hypophosphite and phosphite.

PMID- 18035611
TI  - Postgraduate cardiology training in Turkey. Interview by Judy Ozkan.

PMID- 18035610
TI  - Structure, assembly, and function of the spore surface layers.
AB  - Endospores formed by Bacillus, Clostridia, and related genera are encased in a
      protein shell called the coat. In many species, including B. subtilis, the coat
      is the outermost spore structure, and in other species, such as the pathogenic
      organisms B. anthracis and B. cereus, the spore is encased in an additional layer
      called the exosporium. Both the coat and the exosporium have roles in protection
      of the spore and in its environmental interactions. Assembly of both structures
      is a function of the mother cell, one of two cellular compartments of the
      developing sporangium. Studies in B. subtilis have revealed that the timing of
      coat protein production, the guiding role of a small group of morphogenetic
      proteins, and several types of posttranslational modifications are essential for
      the fidelity of the assembly process. Assembly of the exosporium requires a set
      of novel proteins as well as homologues of proteins found in the outermost layers
      of the coat and of some of the coat morphogenetic factors, suggesting that the
      exosporium is a more specialized structure of a multifunctional coat. These and
      other insights into the molecular details of spore surface morphogenesis provide
      avenues for exploitation of the spore surface layers in applications for
      biotechnology and medicine.

PMID- 18035612
TI  - Spotlight: Gary McVeigh, MD, PhD, FRCP, FRCPI. Interview by Jennifer Taylor.

PMID- 18035614
TI  - [Periodic medical examinations: problem of concordance].
AB  - From bioethics and contemporary medical legislation viewpoints, the authors
      consider a topic of periodic medical examinations and possibility of concordance
      between doctor and patient. Opinion is that in order to gain concordance and
      higher efficiency of the examinations, the doctor should separate occupational
      examination function from medical function.

PMID- 18035615
TI  - [Role of "oxidant-antioxidant" system and genetic biochemical polymorphism in
      pathogenesis of occupational allergic dermatosis].
AB  - Studying "oxidant-antioxidant" system in patients with occupational allergic
      dermatosis revealed hyperactivity of free radical oxidation and depressed
      antioxidant system, especially its nonenzymatic unit. Finding also is high share
      of antibodies to double-stranded DNA in patients with occupational allergic
      dermatosis. Zero genotype of GSTM1 system is characterized by early (up to 5
      years) development,severe course and unfavorable prognosis of occupational skin
      diseases.

PMID- 18035616
TI  - [Information supply for scientific research in occupational medicine].
AB  - Using materials of 2-year comparative study of information supply for scientific
      research in occupational medicine, conducted through social hygienic polls, the
      authors demonstrated peculiarities of informational supply and its significance
      for optimizing the scientific work. Informational supply of scientific research
      in occupational medicine requires complex approach including availability of
      information resources and technologies, increased material and technical basis of
      research organizations, developed intraregional and international cooperation
      with similar national and foreign organizations.

PMID- 18035617
TI  - [The National Project "Health" and reequipment of the Russian medical X-ray
      service].
AB  - Implementation of the National Project "Health" in the area of X-ray diagnostic
      equipment supply to public health organizations is considered. The prospects for
      replacement of outdated X-ray equipment within the framework of the National
      Project are discussed. Advantages of digital X-ray diagnostic equipment and the
      expedience of its wide use in the implementation of the National Project are
      substantiated.

PMID- 18035618
TI  - [Use of stereoscopic vision for analysis of digital X-ray images of lungs].
AB  - The fundamental principles of digital stereoroentgenography are considered. A
      special adapter to digital X-ray diagnostic apparatus used to obtain X-ray
      stereoscopic pairs and Stumpf stereoscopic binoculars for analysis of
      stereoscopic photographs are described. Specific features of the stereoscopic
      model of lungs and an exemplary clinical case are considered.

PMID- 18035619
TI  - Capturing conceptual implicit memory: the time it takes to produce an
      association.
AB  - Conceptual implicit memory is demonstrated when, in the absence of explicit
      retrieval, performance on a task requiring conceptual processing benefits more
      from prior conceptual encoding than from prior nonconceptual encoding. In the
      present study, we sought to provide an improved measure of conceptual implicit
      memory by minimizing contamination from explicit retrieval. On a modified word
      association test, participants free-associated to the actually studied items,
      with response time to produce any associate serving as the dependent measure.
      Experiment 1 varied whether words were read or generated at study and showed that
      generated words were associated to more quickly than were read words. Experiment
      2 varied level of processing at study and showed that words processed
      semantically were associated to more quickly than were words processed
      nonsemantically. With modifications to ensure its implicit nature, a conceptual
      implicit test can be consistently affected by the same encoding manipulations as
      those that affect conceptual explicit memory tests.

PMID- 18035620
TI  - Memory for intention-related material presented in a to-be-ignored channel.
AB  - Three experiments were conducted to investigate the fate of intention-related
      material processed in a to-be-ignored channel. Participants were given an
      intention to respond to cues in a visual-processing stream while simultaneously
      trying to ignore information being presented in an auditory stream. Subsequent to
      the ongoing activity, a surprise recognition test for information presented in
      the to-be-ignored auditory modality was administered. As compared with comparable
      neutral information, corrected recognition memory for intention-related material
      was significantly better, depending on the type of event-based prospective memory
      task. These results suggest that holding certain kinds of intentions can bias
      attentional processes in a manner consistent with a perceptual readiness for
      uptake of intention-related material.

PMID- 18035621
TI  - Recalling episodic and semantic information about famous faces and voices.
AB  - In this study, we used the distinction between remember and know (R/K)
      recognition responses to investigate the retrieval of episodic information during
      familiar face and voice recognition. The results showed that familiar faces
      presented in standard format were recognized with R responses on approximately
      50% of the trials. The corresponding figure for voices was less than 20%. Even
      when overall levels of recognition were matched between faces and voices by
      blurring the faces, significantly more R responses were observed for faces than
      for voices. Voices were significantly more likely to be recognized with K
      responses than were blurred faces. These findings indicate that episodic
      information was recalled more often from familiar faces than from familiar
      voices. The results also showed that episodic information about a familiar person
      was never recalled unless some semantic information, such as the person's
      occupation, was also retrieved.

PMID- 18035622
TI  - Retrieval-based illusory recollections: why study-test contextual changes impair
      source memory.
AB  - Illusory source recollections can be manufactured purely by the conditions at
      retrieval. At encoding, individuals listened to words spoken by a male or a
      female voice and later, at retrieval, determined who initially had spoken the
      test word or whether it was a new word. In Experiment 1, individuals were
      instructed during the memory test to make a response of male or female only if
      they clearly recollected the speaker presenting the item during encoding and to
      respond don't remember otherwise. Presenting test words with the same voice
      (match condition) as the one that had presented the word at encoding, a different
      voice (mismatch condition), or no test voice had no effect on the rate of
      responding don't remember. Instead, matching and mismatching test voices created
      illusory recollections that were consistent with the test voice. Experiment 2
      yielded similar results with a remember/know source test. In this article, a
      theory is proposed that explains the illusory recollection effects, and a
      multinomial model and procedure are used to separate and measure the
      contributions of source discrimination and illusory recollections to performance.

PMID- 18035623
TI  - Lure similarity affects visual episodic recognition: detailed tests of a noisy
      exemplar model.
AB  - Summed-similarity models of visual episodic recognition memory successfully
      predict the variation in false alarm rates across different test items. With data
      averaged across subjects, Kahana and Sekuler demonstrated that subjects'
      performance appears to change along with the mean similarity among study items;
      with high interstimulus similarity, subjects were less likely to commit false
      alarms to similar lures. We examined this effect in detail by systematically
      varying the coordinates of study and test items along a critical stimulus
      dimension and measuring memory performance at each point. To reduce uncontrolled
      variance associated with individual differences in vision, the coordinates of
      study and test items were scaled according to each subject's discrimination
      threshold. Fitting each of four summed-similarity models to the individual
      subjects' data demonstrated a clear superiority for models that take account of
      interitem similarity on a trialwise basis.

PMID- 18035624
TI  - The effects of divided attention on auditory priming.
AB  - Traditional theorizing stresses the importance of attentional state during
      encoding for later memory, based primarily on research with explicit memory.
      Recent research has begun to investigate the role of attention in implicit memory
      but has focused almost exclusively on priming in the visual modality. The present
      experiments examined the effect of divided attention on auditory implicit memory,
      using auditory perceptual identification, word-stem completion and word-fragment
      completion. Participants heard study words under full attention conditions or
      while simultaneously carrying out a distractor task (the divided attention
      condition). In Experiment 1, a distractor task with low response frequency failed
      to disrupt later auditory priming (but diminished explicit memory as assessed
      with auditory recognition). In Experiment 2, a distractor task with greater
      response frequency disrupted priming on all three of the auditory priming tasks
      as well as the explicit test. These results imply that although auditory priming
      is less reliant on attention than explicit memory, it is still greatly affected
      by at least some divided-attention manipulations. These results are consistent
      with research using visual priming tasks and have relevance for hypotheses
      regarding attention and auditory priming.

PMID- 18035625
TI  - A little elaboration goes a long way: the role of generation in eyewitness
      suggestibility.
AB  - Although research has documented that perceptual elaboration (e.g., imagery) can
      increase false memory, prior research has not ascertained whether such effects
      are due to the act of generation or simply from exposure to perceptual details.
      Two experiments explored this question using the eyewitness suggestibility
      paradigm. Experiment 1 compared the effect of generating descriptions of
      suggested items with the effects of reading elaborated versions of the items or
      the suggested items alone. Experiment 2 compared participants who generated
      descriptions to participants who read the same descriptions. Generating a
      description increased false memory and increased accurate memory for the items'
      actual source, relative to comparable control conditions. Generation also
      increased claims of having a (false) vivid recollection of the items in the
      event. Overall, the results suggest that conditions that require people to
      describe the appearance of objects that they do not remember are even more
      pernicious than conditions that involve exposure to such details.

PMID- 18035626
TI  - Buffered forgetting: when targets and distractors are both forgotten.
AB  - In three experiments, we investigated prior findings that, following some memory
      tasks, essentially flat d' or forced-choice retention curves are produced. These
      curves have been interpreted as indicating that forgetting is not present over
      the intervals examined; however, we propose in this article that forgetting is
      actually present whenever hit rates and false alarm rates are both declining,
      despite the result being a flat retention curve. We demonstrate that such curves
      can be produced using a pair recognition procedure, a plurality discrimination
      task, and a verbal discrimination task. For all of these tasks, we provide either
      new evidence or refer to evidence already in the literature that tends to
      contradict alternative explanations. Then we show how the failure to consider
      both signal strength and noise has led to distortions in theoretical thinking
      about forgetting.

PMID- 18035627
TI  - The effect of the frequencies of three consecutive content words on eye movements
      during reading.
AB  - The frequencies of three consecutive content words were simultaneously varied in
      the first sentence of a two-sentence passage. Various eye movement measures of
      first-pass processing (first-fixation duration, gaze duration, and go-past time)
      all revealed frequency effects for all three words. The size of the effect did
      not differ significantly across the three words on either first-fixation duration
      or gaze duration, but it increased markedly for go-past time from the first to
      the second word, possibly indicating an accumulation of the difficulty of
      processing. In addition, there was a delayed effect of the frequency
      manipulation: For the sentences with three low-frequency words, processing at the
      beginning of the next (second) sentence was lengthened. (The beginning of the
      second sentence was always at least four words from the last of the frequency
      manipulated words.) These findings indicate that word frequency has effects
      beyond initial lexical access in reading. A list of the experimental items and
      supplemental analyses may be downloaded from www.psychonomic.org/archive.

PMID- 18035629
TI  - Coherence-driven resolution of referential ambiguity: a computational model.
AB  - We present a computational model that provides a unified account of inference,
      coherence, and disambiguation. It simulates how the build-up of coherence in text
      leads to the knowledge-based resolution of referential ambiguity. Possible
      interpretations of an ambiguity are represented by centers of gravity in a high
      dimensional space. The unresolved ambiguity forms a vector in the same space.
      This vector is attracted by the centers of gravity, while also being affected by
      context information and world knowledge. When the vector reaches one of the
      centers of gravity, the ambiguity is resolved to the corresponding
      interpretation. The model accounts for reading time and error rate data from
      experiments on ambiguous pronoun resolution and explains the effects of context
      informativeness, anaphor type, and processing depth. It shows how implicit
      causality can have an early effect during reading. A novel prediction is that
      ambiguities can remain unresolved if there is insufficient disambiguating
      information.

PMID- 18035628
TI  - Long-range regressions to previously read words are guided by spatial and verbal
      memory.
AB  - To examine the nature of the information that guides eye movements to previously
      read text during reading (regressions), we used a relatively novel technique to
      request a regression to a particular target word when the eyes reached a
      predefined location during sentence reading. A regression was to be directed to a
      close or a distant target when either the first or the second line of a complex
      two-line sentence was read. In addition, conditions were created that pitted
      effects of spatial and linguistic distance against each other. Initial
      regressions were more accurate when the target was spatially near, and effects of
      spatial distance dominated effects of verbal distance. Initial regressions rarely
      moved the eyes onto the target, however, and subsequent "corrective" regressions
      that homed in on the target were subject to general linguistic processing
      demands, being more accurate during first-line reading than during second-line
      reading. The results suggest that spatial and verbal memory guide regressions in
      reading. Initial regressions are primarily guided by fixation-centered spatial
      memory, and corrective regressions are primarily guided by linguistic knowledge.

PMID- 18035630
TI  - Perspective effects in repeated reading: an eye movement study.
AB  - The present study examined the influence of perspective instructions on online
      processing of expository text during repeated reading. Sixty-two participants
      read either a high or a low prior knowledge (HPK vs. LPK) text twice from a given
      perspective while their eye movements were recorded. They switched perspective
      before a third reading. Reading perspective affected the first-pass reading and
      also increased sentence wrap-up processing time in the perspective-relevant
      sentences. Prior knowledge facilitated the recognition of the (ir)relevance of
      text information and resulted in relatively earlier perspective effects in the
      HPK versus LPK text. Repeated reading facilitated processing, as indicated by all
      eye movement measures. After the perspective switch, a repetition benefit was
      observed for the previously relevant text information, whereas a repetition cost
      was found for the previously irrelevant text information. These results indicate
      that reading perspective and prior knowledge have a significant influence on how
      readers allocate visual attention during reading.

PMID- 18035631
TI  - Self-construal and the processing of covariation information in causal reasoning.
AB  - Causal induction provides a nice test domain for examining the influence of
      individual-difference factors on cognition. The phenomena of both
      conditionalization and discounting reflect attention to multiple potential causes
      when people infer what caused an effect. We explored the hypothesis that
      individuals with an independent self-construal are relatively less sensitive to
      context (other causes) than are individuals with an interdependent self-construal
      in this domain. We found greater levels of conditionalization and data consistent
      with discounting for participants in whom we primed an interdependent self
      construal than for participants in whom we primed an independent self-construal.

PMID- 18035632
TI  - Retrieval or nonretrieval strategies in mental arithmetic? An operand recognition
      paradigm.
AB  - According to LeFevre, Sadesky, and Bisanz, averaging solution latencies in order
      to study individuals' arithmetic strategies can result in misleading conclusions.
      Therefore, in addition to classical chronometric data, they collected verbal
      reports and challenged the assumption that adults rely systematically on
      retrieval of arithmetic facts from memory to solve simple addition problems.
      However, Kirk and Ashcraft questioned the validity of such a methodology and
      concluded that a more appropriate method has to be found. Thus, we developed an
      operand recognition paradigm that does not rely on verbal reports or on solution
      latencies. In accordance with LeFevre et al., we show in a first experiment that
      adults resort to nonretrieval strategies to solve addition problems involving
      medium numbers. However, in a second experiment, we show that high-skilled
      individuals can solve the same problems using a retrieval strategy. The benefits
      of our paradigm to the study of arithmetic strategies are discussed.

PMID- 18035633
TI  - Induction as conditional probability judgment.
AB  - Existing research on category-based induction has primarily focused on reasoning
      about blank properties, or predicates that are designed to elicit little prior
      knowledge. Here, we address reasoning about nonblank properties. We introduce a
      model of conditional probability that assumes that the conclusion prior
      probability is revised to the extent warranted by the evidence in the premise.
      The degree of revision is a function of the relevance of the premise category to
      the conclusion and the informativeness of the premise statement. An algebraic
      formulation with no free parameters accurately predicted conditional
      probabilities for single- and two-premise conditionals (Experiments 1 and 3), as
      well as problems involving negative evidence (Experiment 2).

PMID- 18035634
TI  - Paradoxical effects of base rates and representation in category learning.
AB  - The inverse base rate effect (IBRE) continues to be a puzzling case of decision
      making on the basis of conflicting information in human category learning. After
      being trained via feedback over trials to assign combinations of cues to high-
      and low-frequency categories, participants tend to respond with the low-frequency
      category to an otherwise perfectly conflicting pair of test cues, contrary to the
      category base rates. Our Experiment 1 demonstrated that decision making on the
      basis of an explicit summary of the cue-outcome and outcome base rate information
      from the standard learning task does not result in the effect. The remaining
      experimental conditions evaluated the necessary and sufficient conditions for the
      effect by systematically exploring experimental deviations between the standard
      learning task and the pure decision-making task. In partial disagreement with
      both recent theoretical accounts of the effect, these experiments indicate that
      asymmetric outcome representation and profound base rate neglect are individually
      necessary and jointly sufficient conditions. Broader theoretical implications are
      discussed.

PMID- 18035636
TI  - Does causal knowledge help us be faster and more frugal in our decisions?
AB  - One challenge that has to be addressed by the fast and frugal heuristics program
      is how people manage to select, from the abundance of cues that exist in the
      environment, those to rely on when making decisions. We hypothesize that causal
      knowledge helps people target particular cues and estimate their validities. This
      hypothesis was tested in three experiments. Results show that when causal
      information about some cues was available (Experiment 1), participants preferred
      to search for these cues first and to base their decisions on them. When allowed
      to learn cue validities in addition to causal information (Experiment 2),
      participants also became more frugal (i.e., they searched fewer of the available
      cues), made more accurate decisions, and were more precise in estimating cue
      validities than was a control group that did not receive causal information.
      These results can be attributed to the causal relation between the cues and the
      criterion, rather than to greater saliency of the causal cues (Experiment 3).
      Overall, our results support the hypothesis that causal knowledge aids in the
      learning of cue validities and is treated as a meta-cue for identifying highly
      valid cues.

PMID- 18035635
TI  - The role of visuospatial and verbal working memory in perceptual category
      learning.
AB  - The role of verbal and visuospatial working memory in rule-based and information
      integration category learning was examined. Previously, Maddox, Ashby, Ing, and
      Pickering found that a sequentially presented verbal working memory task did not
      affect information-integration learning, but disrupted rule-based learning when
      the rule was on the spatial frequency of a Gabor stimulus. This pattern was
      replicated in Experiment 1, in which the same category structures were used, but
      in which the verbal working memory task was replaced with a visuospatial analog.
      Experiment 2A examined rule-based learning on an oblique orientation and also
      found both verbal and visuospatial working memory tasks disrupting learning.
      Experiment 2B examined rule-based learning on a cardinal orientation and found a
      minimal effect of the verbal working memory task, but a large effect of the
      visuospatial working memory task. The conceptual significance of cardinal
      orientations and the role of visuospatial and verbal working memory in category
      learning are discussed.

PMID- 18035637
TI  - Canceling updating in the comprehension of counterfactuals embedded in
      narratives.
AB  - Participants were given counterfactual sentences--for example, "If Mary had won
      the lottery she would have bought a Mercedes car"--or factual sentences--for
      example, "Because Mary won the lottery, she bought a Mercedes car"--embedded in
      short narratives. Reading times showed that readers were immediately sensitive to
      the special status of counterfactual information (Experiment 1). In addition,
      probe-recognition latencies demonstrated that old information was more accessible
      in counterfactual than in factual stories, and new information was equally
      accessible in both kinds of stories (Experiment 2). However, after reading
      additional clauses, new information became less accessible in counterfactual than
      in factual stories (Experiment 3). These results suggest that counterfactual
      events are momentarily represented but are later suppressed and the readers'
      attention goes back to previous events in the story.

PMID- 18035639
TI  - First-perspective spatial alignment effects from real-world exploration.
AB  - When spatial knowledge is acquired from secondary-learning media, such as text,
      people sometimes remember a route in alignment with the first perspective or
      first direction of travel. However, this first-perspective alignment (FPA) effect
      has been found only under special circumstances from primary real-world
      exploration. In Experiment 1, recall of an enclosed small-scale, U-shaped route
      was compared following learning from a verbal description, a video recording, or
      real-world exploration; an FPA effect was found in all cases. In Experiments 2
      and 3, exploration of physically larger real routes led to statistically
      significant evidence of an FPA effect when the route was enclosed, but not when
      cues external to the route were available. The data are discussed in relation to
      current theories of spatial reference frames.

PMID- 18035640
TI  - Analogical reasoning in working memory: resources shared among relational
      integration, interference resolution, and maintenance.
AB  - We report a series of experiments using a pictorial analogy task designed to
      manipulate relational integration, interference resolution, and active
      maintenance simultaneously. The difficulty of the problems was varied in terms of
      the number of relations to be integrated, the need for interference resolution,
      and the duration of maintenance required to correctly solve the analogy. The
      participants showed decreases in performance when integrating multiple relations,
      as compared with a single relation, and when interference resolution was required
      in solving the analogy. When the participants were required to integrate multiple
      relations while simultaneously engaged in interference resolution, performance
      was worse, as compared with problems that incorporated either of these features
      alone. Maintenance of information across delays in the range of 1-4.5 sec led to
      greater decrements in visual memory, as compared with analogical reasoning.
      Misleading information caused interference when it had been necessarily attended
      to and maintained in working memory and, hence, had to be actively suppressed.
      However, sources of conflict within information that had not been attended to or
      encoded into working memory did not interfere with the ongoing controlled
      information processing required for relational integration. The findings provide
      evidence that relational integration and interference resolution depend on shared
      cognitive resources in working memory during analogical reasoning.

PMID- 18035638
TI  - Early development of perceptual expertise: within-basic-level categorization
      experience facilitates the formation of subordinate-level category
      representations in 6- to 7-month-old infants.
AB  - A behavioral manifestation of perceptual expertise is the shift in recognition
      downward toward the subordinate level. Here, a familiarization-novelty preference
      procedure was used to determine whether 6- to 7-month-old infants could be
      induced to form category representations for cats and dogs at the subordinate
      level. In Experiment 1, the infants succeeded in forming subordinate-level
      category representations for beagle dogs and Siamese cats, but only when provided
      with previous experience on a subordinate-level category-formation task from
      within the same basic-level category (i.e., Saint Bernard dogs or tabby cats).
      When the prior category-formation task involved a different basic-level category,
      subsequent subordinate-level category learning was not in evidence. The
      preferences in Experiment 1 were shown in Experiments 2 and 3 not to be
      attributable to a priori preference or within-category discrimination failure.
      The findings suggest that within-basic-level categorization experience can
      facilitate the formation of subordinate-level category representations in the
      first half-year of life.

PMID- 18035641
TI  - Effects of working memory capacity on mental set due to domain knowledge.
AB  - The present set of studies examines how working memory capacity (WMC) relates to
      performance on a Remote Associates Task (RAT), originally designed by Mednick as
      a quantifiable creative problem solving assessment. The source of fixation was
      manipulated across two sets of RAT items. One set was neutral with no specific
      fixation embedded in them, while the second set was baseball-misleading, designed
      so that prior knowledge of baseball would lead to an incorrect solution attempt.
      WMC scores were positively related to performance on RAT items in all conditions,
      except one. High baseball knowledge participants' WMC scores did not relate to
      performance on the baseball-misleading RAT. While in general WMC may lead to
      better RAT performance, these results suggest that when there is a candidate
      solution strongly activated by prior knowledge, WMC may actually lead to too much
      focus on the incorrect solution and exacerbate mental sets.

PMID- 18035642
TI  - Influences on the Simon effect of prior practice with spatially incompatible
      mappings: transfer within and between horizontal and vertical dimensions.
AB  - The Simon effect refers to the fact that for tasks in which stimulus location is
      irrelevant and a nonspatial attribute is relevant, responses are typically faster
      when stimulus and response locations correspond than when they do not. Two
      experiments examined the influence of prior practice with an incompatible
      relevant spatial mapping on the Simon effect as a function of the dimension
      (vertical or horizontal) along which the stimuli and responses varied in practice
      and transfer sessions. With 72 practice trials, the Simon effect in the transfer
      session was eliminated only when the spatial dimension was horizontal for both
      practice and transfer. With 600 practice trials, the Simon effect was eliminated
      for all combinations of practice and transfer dimensions, with noncorresponding
      responses showing an advantage when the dimension was horizontal for both
      practice and transfer. Within-dimension transfer effects for the horizontal
      dimension after a small amount of practice can be attributed to reactivation of
      specific stimulus-response associations defined for the practice task. However,
      the between-dimension transfer effects evident after a larger amount of practice
      cannot be explained in this manner and suggest that the subjects acquired a
      general procedure of responding opposite to the stimulus location.

PMID- 18035643
TI  - Color and context: an ERP study on intrinsic and extrinsic feature binding in
      episodic memory.
AB  - Episodic memory for intrinsic item and extrinsic context information is
      postulated to rely on two distinct types of representation: object and episodic
      tokens. These provide the basis for familiarity and recollection, respectively.
      Electrophysiological indices of these processes (ERP old-new effects) were used
      together with behavioral data to test these assumptions. We manipulated an
      intrinsic object feature (color; Experiment 1) and a contextual feature
      (background; Experiments 1 and 2). In an inclusion task (Experiment 1), the study
      test manipulation of color affected object recognition performance and modulated
      ERP old-new effects associated with both familiarity and recollection. In
      contrast, a contextual manipulation had no effect, although both intrinsic and
      extrinsic information was available in a direct feature (source memory) test.
      When made task relevant (exclusion task; Experiment 2), however, context affected
      the ERP recollection effect, while still leaving the ERP familiarity effect
      uninfluenced. We conclude that intrinsic features bound in object tokens are
      involuntarily processed during object recognition, thus influencing familiarity,
      whereas context features bound in episodic tokens are voluntarily accessed,
      exclusively influencing recollection. Figures depicting all the electrodes
      analyzed are available in an online supplement at www.psychonomic.org/archive.

PMID- 18035644
TI  - Characterizing sequence knowledge using online measures and hidden Markov models.
AB  - What knowledge do subjects acquire in sequence-learning experiments? How can they
      express that knowledge? In two sequence-learning experiments, we studied the
      acquisition of knowledge of complex probabilistic sequences. Using a novel
      experimental paradigm, we were able to compare reaction time and generation
      measures of sequence knowledge online. Hidden Markov models were introduced as a
      novel way of analyzing generation data that allowed for a characterization of
      sequence knowledge in terms of the grammar that was used to generate the stimulus
      material. The results indicated a strong correlation between the decrease in
      reaction times and an increase in generation performance. This pattern of results
      is consistent with a common knowledge base for improvement on both measures. On a
      more detailed level, the results indicate that at the start of training,
      generation performance and reaction times are uncorrelated and that this
      correlation increases with training.

PMID- 18035645
TI  - Orientation unbound: dissociation of identity and orientation under rapid serial
      visual presentation.
AB  - Participants were shown rapid sequences of three letters, flanked by digits, each
      rotated 0 degree, 90 degrees, 180 degrees, or 270 degrees clockwise from upright.
      In Experiment 1, the participants tried to report the letter that matched the
      orientation of an arrow, presented either before (before task) or after (after
      task) the sequence. A third task (total task) required them to report all of the
      letters. Accuracy for individual letters was significantly better in the total
      task than in the before task, and better in the before task than in the after
      task, suggesting particular difficulty in binding orientation to identity. In
      Experiment 2, the participants were given letter probes and were asked to
      indicate the orientation of the probed letter. Although report was above chance,
      there were frequent illusory conjunctions. Since perception of orientation must
      depend on prior establishment of identity, our results suggest that orientation
      and identity may become unbound during processing and are held in parallel
      storage systems.

PMID- 18035646
TI  - Kinetic characterization of extracellular alpha-amylase from a derepressed mutant
      of Bacillus licheniformis.
AB  - Three strains of Bacillus licheniformis were isolated and screened for alpha
      amylase production by solid-state fermentation. Of these, IS-2 gave relatively
      higher enzyme production (32+/-2.3 U/[g.min]) and was selected for improvement
      after treatment with N-methylnN-nitro N-nitroso guanidine (NG) or nitrous acid
      (NA) to enhance its hydrolytic potential. Among the mutant variants, NA-14 gave
      higher enzyme production (98+/-1.6 U/[g.min]), and hence, was selected for
      kinetic and thermal characterization. M1 as a moistening agent (pH 7.0,
      optimized) supported 2.65-fold improved amylolytic activity by the derepressed
      mutant 72 h after inoculation. The values of product yield coefficient (Y p/x =
      1833.3 U/g) and specific rate constant (qp = 25.46 U/[g.h]) with starch were
      severalfold improved over those from other carbon sources and the other cultures.
      The purified enzyme from NA-14 was most active at 40 degrees C; however, the
      activity remained almost constant up to 44 degrees C. The NA-induced random
      mutagenesis substantially improved the enthalpy (DeltaH D = 94.5+/-11 kJ/mol) and
      entropy of activation (DeltaS = -284+/-22J/[mol.K]) for alpha-amylase activity
      and substrate binding for starch hydrolysis. The results of this study (117.8+/
      5.5 U/[g.min]) revealed a concomitant improvement in the endogenous metabolism of
      the mutant culture for alpha-amylase production.

PMID- 18035647
TI  - Outbreak and spread  of chikungunya.

PMID- 18035648
TI  - Influenza.

PMID- 18035649
TI  - [Prosthetic valve dysfunction with atypical symptoms. Endocarditis or
      thrombosis?].

PMID- 18035650
TI  - Improving patient care: measurement of outcome in rheumatoid arthritis.
AB  - Although most people who are seen in rheumatology clinics are suffering from
      fatigue, pain, functional disability and/or psychological distress, fewer than
      15% of healthcare professionals collect any formal quantitative information
      concerning these problems. In contrast with acute disease in hospital settings
      where quantitative data concerning functional status or pain are unnecessary, as
      success or failure of the treatment is obvious within a short period, chronic
      diseases form a different challenge. Patient-reported outcomes are an attractive
      option in a busy medical practice, as the time burden is transferred from the
      clinician to the patient. Furthermore, such information is critical in the
      documentation of patient outcomes and results of care. This work was carried out
      to analyse a developed version of a multi-dimensional health assessment
      questionnaire. This questionnaire has been edited in a 'patient-friendly' format
      and its applicability is for standard use in a nurse-led clinical practice to
      monitor patients suffering from chronic inflammatory conditions in a busy
      rheumatology unit of a district general hospital.

PMID- 18035651
TI  - [Patient information: hepatitis B, hepatitis C, and pregnancy].

PMID- 18035652
TI  - [Unknown origin fever and lichen planus in penis].

PMID- 18035653
TI  - [Fever without center in patient with chronic pain].

PMID- 18035654
TI  - [Bilateral achilles tendon disorders secondary to levofloxacin].

PMID- 18035656
TI  - Islamic roots to the theory of evolution: the ignored history.

PMID- 18035655
TI  - [The Galician woman in Cuba: from exclusion to protection, 1898-1968].

PMID- 18035657
TI  - How to conduct valid experiments in environmental stress/pollution monitoring
      studies: stumbling-blocks and sampling designs.

PMID- 18035658
TI  - Nine-month radiographic evaluation and comparison of bovine-derived inorganic
      microchips and beta-tricalcium phosphate granules grafted into a maxillary sinus:
      a case report.

PMID- 18035659
TI  - What are my cosmetic options?

PMID- 18035660
TI  - Dentistry 101.

PMID- 18035661
TI  - Dentistry prepared for special situations.

PMID- 18035663
TI  - FDA dentists: bringing bright smiles to the sunshine state.

PMID- 18035662
TI  - What your mouth says about your body.

PMID- 18035664
TI  - Dentistry offers variety of options to keep teeth healthy for a lifetime.

PMID- 18035665
TI  - Florida Dental Association has deep roots, rich history.

PMID- 18035666
TI  - Arthritis research: methods and protocols. Preface.

PMID- 18035668
TI  - [Pathology in Wuppertal].

PMID- 18035669
TI  - [Molecular genetics and clinics of hereditary breast cancer].
AB  - Breast cancer is a heterogenous disease caused by mutations in tumor associated
      genes. While the vast majority of breast carcinomas occur sporadically, about 5%
      are attributable to dominant susceptibility alleles. Two major genes, BRCA1 and
      BRCA2, have been identified and account for a risk of up to 80% for breast cancer
      and up to 40% for ovarian cancer. Molecular genetic diagnosis allows the
      identification of women at risk that can be offered predictive meassures.
      Predictive strategies comprise primary, secondary and tertiary care. While data
      on medical prevention are still pending in this risk group, intensive
      surveillance and prophylactic surgery are proven to be effective in early tumor
      detection and reduction of incidence rates, respectively. However, there is
      little or no data regarding the efficacy of these procedures in terms of survival
      and quality of life. The German Hereditary Breast and Ovarian Cancer Consortium
      supported by the German Cancer Aid addresses these issues in a prospective cohort
      study with a standardized enrollment, prevention and follow up protocol. Results
      are presented in light of recent developments.

PMID- 18035670
TI  - Classification and grading of invasive breast carcinoma.
AB  - The main reasons for applying a classification system to invasive breast
      carcinoma are to obtain a correlation with prognosis and tumour biology. Invasive
      carcinomas may be sub-divided morphologically according to their degree of
      differentiation. This is achieved in two ways, by assessing histological type and
      histological grade. A wide range of histological patterns is recognised in
      invasive carcinoma of the breast and four broad prognostic groups are recognised:
      the excellent prognosis group comprises tubular, cribriform, mucinous carcinomas;
      the good group tubular mixed, mixed ductal NST/special type and classical lobular
      carcinoma; the average group mixed lobular, medullary and atypical medullary
      carcinoma and the poor group is composed of ductal NST, mixed ductal and solid
      lobular carcinoma understanding of the biology of breast cancer. For example,
      tumours with a medullary phenotype which express basal cytokeratins and are p53
      positive and ER and c-erbB-2 negative are strongly predictive of the BRCA-1 gene
      mutation carrier state. Histological grading refers to the semi-quantitative
      evaluation of the morphological structure of breast carcinomas. In the Nottingham
      method three characteristics of the tumour are evaluated, glandular
      differentiation, nuclear pleomorphism and mitotic counts. A numerical scoring
      system on a scale of 1-3 is used to ensure that each factor is assessed
      individually. Overall grade is assigned as follows: Grade 1: 3-5 points, Grade 2:
      6-7 points, Grade 3: 8-9 points. There is a highly significant relationship
      between histological grade and prognosis; survival worsens with increasing grade.
      Histological grading has been shown to have good reproducibility and has been
      adopted for use in Europe, Australasia and the United States. When combined with
      pathological tumour size and lymph node stage into the Nottingham Prognostic
      Index there is excellent stratification for patient management.

PMID- 18035671
TI  - Ck5-positive cells are precursor cells of glandular and myoepithelial cell
      lineages in the human breast epithelium. A new cell concept as a basis for a
      better understanding of proliferative breast disease?
AB  - The question of whether stem cells exist in the human breast has never been
      satisfactorily resolved. Using a double immunofluorescence technique for
      simultaneous demonstration of cytokeratin subgroups 5, 8/18/19 and the
      differentiation marker smooth muscle actin, we provided direct evidence of the
      existence of a Ck5-positive cells that differentiate to either the glandular or
      myoepithelial cell lineage via intermediary cells. We postulate that the Ck5
      positive cells are phenotypically and behaviourally committed adult stem cells.
      We further provide evidence that benign proliferative breast disease lesions
      resemble normal breast epithelium, whereas most breast carcinomas phenotypically
      consist of glandularly differentiated cells. The results were corroborated
      biochemically by Western blotting techniques. This cell biological model provides
      a new tool which helps to distinguish benign and malignant breast lesions.
      Furthermore this model provides a basis to unravel the regulatory mechanisms that
      govern normal and pathological cell growth.

PMID- 18035672
TI  - [Radiological features of breast cancer].
AB  - When considering typical features of malignant lesions, the radiologist must
      differentiate between invasive cancers consisting of mass lesions and ductal
      carcinoma in situ, typically appearing as microcalcifications. Common malignant
      features of invasive cancers include irregular shape and indistinct or spiculated
      margins. In microcalcifications, segmental distribution and pleomorphic shape are
      the features with the highest predictive value of malignancy. However, there is a
      broad spectrum of findings that confound the reliable differentiation between
      benign and malignant lesions. The American College of Radiology has established
      the Breast Imaging Reporting and Data System (BI-RADS) for standardizing
      radiological terms and reports in mammography screening. The Breast Imaging
      Reporting and Data System provides diagnostic categories that have implications
      for guidance regarding follow-up or biopsy of mammographic breast lesions. BI
      RADS 3 lesions are considered probably benign with a malignancy risk < 2%. These
      findings can be followed up at predetermined intervals according to current
      recommendations. Suspicious lesions with a substantial probability, but without
      the classic appearance of malignancy, are classified as BI-RADS 4. Minimal
      invasive biopsy should be considered in patients with these lesions. BI-RADS 5
      lesions are highly suggestive of malignancy. It is recommended that appropriate
      action should be taken for these most suspicious lesions. The accuracy of the
      mammography as the primary diagnostic tool can be increased by the use of
      ultrasound and physical examination. In some situations, MRI is helpful for
      further evaluation. However, classifying the lesions with precision is not
      trivial since overlap exists between malignant and benign features.

PMID- 18035673
TI  - [Tissue-based markers of prognosis in breast cancer].
AB  - Precise prognostication represents one of the essential but still unsolved
      challenges in breast cancer pathology. There is a striking discrepancy between
      the plethora of suggested markers that have proved useful in mono-centre
      retrospective studies, including molecular expression arrays and the only small
      number of parameters applied in clinical decision finding. When adjuvant therapy
      is considered clinicians still rely predominantly on traditional parameters like
      staging and hormonal receptor status. Another traditional marker which has proven
      its strength in mono-centre studies but is compromised by subjectivity and
      limited reproducibility is provided by grading. We have conducted a study on how
      traditional grading markers can be objectified and adapted to small amounts of
      tissue which have become custom with the wide-spread use ob needle biopsies. A
      modified grading scheme replacing mitosis counting by Ki-67 immunohistochemistry
      and nuclear pleomorphism by digital determination of nuclear size was applied to
      346 cases of breast cancer with a median follow-up of 6 years in a tissue micro
      array. A highly significant correlation with overall and disease-free survival
      could be established in this retrospective study although not more than 1.4
      square millimeters of tissue were evaluated. When combined with nodal status and
      progesterone receptor evaluation a subgroup free of any relapse could be
      identified. It is concluded that standardized and objectified application of
      grading as a traditional tissue-based marker of prognosis can improve its impact
      considerably even in limited amounts of tissue.

PMID- 18035674
TI  - [Recent therapeutic options and expectations to the pathologist].
AB  - The treatment of patients with breast cancer has progressively become
      multidisciplinary. Considering that the establishment of standards of care for
      medical treatment is a process of building consensus by using the best available
      scientific evidence, multidisciplinary guidelines have been developed in Germany
      to promote better and more consistent management of breast cancer patients
      (www.krebsgesellschaft.de). These guidelines provide a framework for clinical
      decision-making and pathological assessment that gives clinically useful and
      prognostically significant information. The improvement of standards of care is
      subject to the definition of procedures at the interface between the different
      involved disciplines. The following topics at the surgery-pathology interface are
      critical for the optimal management of breast cancer and should be coordinated,
      especially with regard to breast conserving therapy: 1. Unequivocal marking of
      the tissue specimens by the surgeon in order to obtain proper orientation. 2.
      Intra-operative frozen sectioning. 3. Residual tumour (R) classification (UICC,
      2002) and adequate distance to resection margins (for DCIS and invasive
      carcinomas). 4. Specific requirements on the pathological examination of surgical
      specimens after primary systemic treatment (neoadjuvant chemotherapy), i. e. the
      assessment of tumour response and the extent and distribution of tumour residues.

PMID- 18035675
TI  - [Minimal residual disease in breast cancer: detection and clinical relevance].
AB  - Hematogenous distant metastasis is the leading cause of cancer-related death in
      breast cancer and other solid tumours. By applying sensitive immunocytochemical
      and molecular assays disseminated tumour cells (DTC) in bone marrow (BM) can be
      detected in 20-40% of cancer patients without any clinical or even
      histopathological signs of metastasis. The detection and characterisation of DTC
      in BM may lead to a better understanding of the biology initiating metastatic
      spread in cancer patients and will eventually contribute to the development of
      more effective strategies to eliminate DTC. In this review, we will therefore
      discuss the detection, characterisation and clinical relevance of DTC.

PMID- 18035676
TI  - [Molecular carcinogenesis of ovarian carcinoma].
AB  - Correlating histological phenotype and molecular pathology epithelial ovarian
      tumours can be classified into a number of subgroups. High grade serous and
      endometrioid carcinomas are characterized by chromosomal instability which is due
      to functional loss of BRCA1/2 and TP53 mutations. The pattern of molecular
      aberrations of carcinosarcomas (Malignant mullerian mixed tumours) is similar to
      high grade serous carcinomas. In contrast serous borderline tumours and low grade
      serous carcinomas only rarely harbour complex genetic alterations. In most of
      these tumours the RAS-RAF signalling cascade is activated either by KRAS or by
      BRAF point mutation. Low grade endometrioid ovarian carcinomas contain the same
      molecular alterations as endometrioid carcinomas of the endometrium, in
      particular beta-catenin and PTEN mutations. Thus, on the molecular level they
      differ significantly from high grade endometrioid carcinomas of the ovary.
      Mucinous adenomas, borderline tumours and carcinomas are all characterized by
      KRAS mutations. Regarding the putative pathways of tumorigenesis a borderline-
      carcinoma sequence is likely for mucinous tumours and low grade serous carcinomas
      of the ovary. Low grade endometrioid carcinomas may originate from ovarian
      endometriosis. High grade endometrioid and serous carcinomas as well as
      carcinosarcoma putatively develop directly (de novo) from the ovarian surface
      epithelium or inclusion cysts.

PMID- 18035677
TI  - Borderline tumors of the ovary and peritoneal implants.
AB  - The new WHO series on Pathology and Genetics of Tumours of the Breast and Female
      Genital Organs (33) defined to name the group of epithelial ovarian tumors with a
      dignity between benign and malignant exclusively as Borderline Tumors of the
      Ovary (BOT) and to skip the term "... of low malignant potential". Further, the
      term "atypical proliferative tumour" was not recommended by the WHO. During a
      Consensus Meeting on Borderline Tumors of the Ovary held at Bethesda on August 27
      28, 2003 (2) the expert panel also recommended to use the BOT terminology.
      However the term "tumour of low malignant potential" and--less favourable-
      "atypical proliferative tumour" may be used as synonym. Both groups agreed
      unanimously that the name carcinoma should not be included in the diagnosis. The
      group of borderline ovarian tumors is heterogeneous. 80 to 90% of the cases have
      a very favourable prognosis while 10-20% exhibit a recurrent clinical course with
      peritoneal implants and very rarely death from the tumor within 10 years. The
      morphological criteria and supporting methods for recognizing unfavorable BOT and
      for distinguishing them from highly differentiated ovarian carcinomas are
      summarized. The prognostic importance of peritoneal implants is described. The
      concept of micropapillary serous carcinomas (MPSC) and its implications on the
      diagnostic work of pathologists will be discussed. The presented data focus on
      serous tumors since this is by far the most common variant.

PMID- 18035678
TI  - [Prognostic factors in ovarian carcinoma].
AB  - Ovarian carcinoma is the most lethal gynaecological malignancy in the western
      world with a five year survival rate of appr. 35 %. Unfortunately, most patients
      present with advanced disease, and their standard treatment is maximal surgical
      debulking and chemotherapy consisting of carboplatin and taxol. The most
      important prognostic factor in these patients is residual tumor after primary
      surgery. In patients with ovarian carcinoma confined to the ovary prognostic
      factors are important. Currently, high-grade and clear cell histology are
      regarded as worse prognostic factors, and these patients receive chemotherapy.
      Studies on prognostic factors in ovarian carcinomas are usually hampered by a low
      number of patients, and the lack of essential data (residual tumor, chemotherapy,
      and histological type), making meta-analyses impossible. For the future,
      prospective studies on putative prognostic factors are necessary. Moreover, for
      patients with advanced disease the evaluation of predictive factors
      (chemoresistance) as well as studies on the importance of the inflammatory
      background present in the tumor-seeded peritoneal cavity will get important.

PMID- 18035679
TI  - [The impact of the pathologist on the treatment of epithelial ovarial cancer].
AB  - The majority of patients with epithelial ovarian cancer (EOC) are diagnosed with
      advanced disease involving sites such as the upper abdomen, pleural space, and
      paraaortic lymph nodes. The standard therapy for advanced disease requires
      maximal cytoreductive surgery followed by postoperative platinum- and taxane
      based chemotherapy. Despite maximal primary surgical effort and postoperative
      standard chemotherapy long-term survival of patients with advanced stage III or
      IV disease ranges from 30% to less than 10% due to early and late relapse or
      primary progressive disease. Facing the highly lethal nature of epithelial
      ovarian carcinoma, the clinical course of advanced disease is difficult to
      predict in an individual patient. This heterogeneity of clinical outcome in
      patients with ovarian carcinoma suggests that reliable prognostic and/or
      predictive factors would be of potential clinical value and new treatment options
      are warranted in the future. In the light of recently published studies we
      summarize the clinical features and the diagnostic, operative and postoperative
      management of epithelial ovarian carcinoma. We furthermore address the importance
      of the pathologist during the clinical course of patients with ovarian carcinoma.
      The issue of timing between surgery and chemotherapy in the setting of
      neoadjuvant chemotherapy treatment of advanced ovarian carcinoma is being
      highlighted as well as the significance of new diagnostic and therapeutic options
      with regard to accurate predictive markers, that might identify patients who are
      appropriate candidates for novel therapeutic approaches.

PMID- 18035680
TI  - [Molecular targets for diagnostics and therapy--new challenges for pathologists].
AB  - During the last decade significant progress in molecular genetics and cell
      biology was made and numerous signal transduction pathways regulating cell
      growth, differentiation and survival were identified. It is now fairly well
      understood how accumulation of multiple genetic aberrations lead to deregulation
      of these signal transduction pathways and cause malignant transformation and
      tumour progression. Therefore, in many cases specific tumour phenotypes can be
      linked to specific genetic changes. As a result molecular diagnostics has become
      an important tool for tumour diagnositics that helps to discriminate specific
      entities. Further, determination of critical mutations leading to activation of
      important growth and survival signals can identify targets for specific tumour
      therapies. Gastrointestinal stromal tumours (GISTs) provide an excellent example
      of how activating mutations in receptor tyrosine kinases can be used as a tool to
      predict tumour biology and response to therapy by receptor inhibitors. During
      therapy secondary receptor mutations may cause resistance to therapy and thus may
      require additional combinatorial therapies. Therefore, predictive pathology and
      monitoring response to novel targeted therapies provide new challenges for
      pathologists and require a broad spectrum of techniques in molecular pathology.

PMID- 18035681
TI  - Biochip analysis: status quo.
AB  - Biochips are collections of miniaturized test sites (microarrays) arranged on a
      solid substrate onto which a large number of biomolecules are attached with high
      density. Like a computer chip performing millions of mathematical operations in a
      few split seconds, a biochip allows for simultaneous analyses of thousands of
      biological reactions, such as decoding genes, in a few seconds. Biochip
      technologies can be applied to numerous fields including genomic, proteomic, and
      glycomic research, as well as pharmacology and toxicology. However, one of the
      most common applications is in the determination of gene expression in human
      cells and tissues. Global gene expression analysis has helped to identify
      important genes and signalling pathways in human malignant tumors. And there is
      hope that microarrays will make the step from "the (laboratory) bench to the
      bedside (of the patient)". Recent studies have indeed revealed that analysis of
      differential gene expression by microarrays may help to identify subtypes of
      malignant tumors, that allow a risk stratification of the patients. However,
      there are several issues that need to be addressed before microarrays may become
      a tool for routine diagnostics, such as problems with bioinformatic analysis,
      construction of disease or tissue specific microarrays with only limited numbers
      of genes of interest, standard operation procedures for tissue preparation to
      prevent RNA degradation, etc.. In this article, an overview over of the
      multifarious biochip applications and technologies, its limitations, challenges
      and future developments is provided.

PMID- 18035682
TI  - [CUP syndrome: are there advances?].
AB  - Metastatic cancer of unknown primary site (CUP syndrome) comprises 2-5% of all
      solid malignant tumors. One should distinguish between initial CUP (primary tumor
      later detected) and the true CUP syndrome (primary tumor remains unknown for a
      patient's lifetime despite thorough diagnostic work-up). For initial CUP, the
      most important auxiliary diagnostic method is immunohistochemistry, which should
      be applied in a two-step algorithmic fashion. Firstly, a small marker panel
      (including certain cytokeratins) yields a preliminary categorization of the
      tumor. Secondly, selective, organ-specific markers (including recently
      established markers such as TTF-1 and uroplakin) and further tumor group markers
      may further subclassify or even identify the primary tumor. Although they are a
      heterogeneous group, true CUP tumors share some unique biological features such
      as an early metastatic phenotype and unusual metastasis patterns, and they mostly
      have a very poor prognosis. Even autopsy reveals the primary site in only 55-80%
      of cases, most commonly in the lung and pancreas. True CUP tumors, predominantly
      adenocarcinomas and poorly differentiated carcinomas, may exhibit unusual
      immunohistochemical phenotypes. Nevertheless, careful histologic and
      immunohistochemical examination are essential not only for determining the actual
      tumor immunophenotype but in particular for identifying therapy-responsive
      subgroups such as neck lymph node CUP, axillary lymph node CUP of females,
      neuroendocrine CUP, and germ cell tumor CUP of males. For CUP syndrome, future
      interdisciplinary research efforts are needed, such as gene expression profiling
      using microarrays. It is thus to be hoped that pathology will contribute to the
      elucidation of the largely still enigmatic pathogenesis of the CUP syndrome, to
      improve its diagnosis and classification and, finally, to aid in the development
      of more specific therapeutic regimens.

PMID- 18035683
TI  - [Alcoholic and non-alcoholic steatohepatitis].
AB  - Morphologic criteria of steatohepatitis are steatosis, ballooning of hepatocytes,
      often but not constantly associated with Mallory bodies, pericellular fibrosis
      and inflammation. Liver cirrhosis follows in about 20-50%. With respect to
      etiology an alcoholic and non-alcoholic type can be distinguished, the latter
      being a characteristic hepatic lesion associated with the metabolic syndrome
      (type II diabetes, insulin resistance, obesity, dyslipidemia). Ballooning of
      hepatocytes as well as Mallory body formation are associated with a disturbance
      of the keratin intermediate filament cytoskeleton. Mallory bodies are protein
      aggregates consisting of keratin (particularly keratin 8), p62, a stress-induced
      adapter protein involved in signal transduction pathways, heat shock proteins,
      and ubiquitin. Oxidative stress is involved in Mallory body formation. Major
      sources of oxidative stress in alcoholic and non-alcoholic steatohepatitis are
      the microsomal biotransformation system (cytochrome P-450) and the mitochondria,
      together with an impaired antioxidant defense system. Oxidative stress leads to
      misfolding/unfolding, abnormal phosphorylation of keratins and disturbance of
      keratin 8: keratin 18 ratio, and thus interferes with intermediate filament
      assembly. Moreover, impairment of cellular defense against abnormal proteins, i.
      e. chaperone action and proteasomal degradation, leads to the accumulation of
      abnormal aggregation--prone keratins (particularly keratin 8) which after
      ubiquitination associate with the stress-induced ubiquitin-binding protein p62 to
      form Mallory bodies. Thus, Mallory body formation resembles an "off-folding"
      protein response of the amyloid type. These pathogenetic principles of the human
      disease are supported by immunohistochemical and gene expression studies in
      experimental animals and by transfection experiments in tissue culture cells.

PMID- 18035684
TI  - [Pathogenesis and pathomorphology of chronic viral hepatitis].
AB  - Chronic viral hepatitis represents the most common liver disease worldwide. It
      can be induced by HBV (eventually as HDV-coinfection) and HCV. From the
      pathologist's point of view chronic hepatitis represents portal accentuated
      inflammation of the liver associated with a variable degree of interface
      hepatitis and acinar damage. Although much research has been done to unravel the
      mechanisms which cause chronic viral hepatitis, many questions are unanswered. Up
      to now, liver biopsy is the gold standard for diagnosis of chronic viral
      hepatitis. On one hand it shows the grade of inflammation and the stage of
      disease, on the other hand it can highlight additional liver diseases, which
      might have an adverse influence. Therefore, liver biopsy allows the best
      prediction of disease progression. In a recent consensus statement, the scoring
      system of Desmet was recommended for grading and staging of chronic hepatitis.

PMID- 18035685
TI  - [Autoimmune hepatitis and autoimmune cholangitis].
AB  - Autoimmune liver diseases encompass autoimmune hepatitis, primary biliary
      cirrhosis (PBC) and primary sclerosing cholangitis (PSC) as lesions of the
      biliary tract. The term autoimmune cholangitis has not been generally accepted,
      so it remains an entitiy waiting for precise definition. AIH is a chronic
      progressive necroinflammatory liver disease mostly occuring in female individuals
      and leading to ultimate autodestruction of the liver if not treated.
      Histopathology of the liver reflects the gerneral understanding of the underlying
      immune especially self reactive CD4 + T-helper cells mediated mechanisms in
      destruction of liver cells displaying a typical but by no means pathognomonic
      histopathological pattern. Since there are no specific and generally valid tests
      the diagnosis should be confirmed by a scoring system including histopathology.
      Variants of autoimmune hepatitis cover seronegative cases, acute onset autoimmune
      hepatitis and autoimmune hepatitis with centrilobular necrosis. Differential
      diagnosis of autoimmune hepatitis includes drug induced chronic hepatitis that
      may mimick autoimmune hepatitis by clinical course and serology. Histopathology
      may give helpful hints for the correct diagnosis. Autoimmune lesions of the
      biliary tract are PBC in the first line. The target antigen of the autoimmune
      response has been identified, natural history of the diseases is well known and
      histopathology is pathognomonic in about a third of the cases. In clinical
      practice liver biopsy is taken to exclude other etiologies when AMA is present in
      the serum, staging the disease at first diagnosis and to establish diagnosis in
      cases of AMA negativity. The autoimmune nature of PSC has been discussed in the
      literature ever since the first description and the answer in not settled yet.
      Histopathology is relevant for the diagnosis in excluding other etiologies and
      confirming the diagnosis of small duct PSC. The term autoimmune cholangitis has
      been used to designate AMA-negative PBC, however, based on research experience
      and the clinical data it should be reserved to the overlap syndrome of AIH and
      PSC in children that seem to make up a disease entitiy of its own.

PMID- 18035686
TI  - [Tumours and inflammatory liver diseases].
AB  - Several tumour entities have been described to develop in chronic inflammatory
      disease mainly hepatocellular carcinoma in chronic hepatitis. Compared to HCC
      bile duct carcinomas or other tumour entities are rare. The risk for HCC
      increases if liver cirrhosis occurred. Despite a huge progress in detecting many
      genes involved and altered in hepatocarcinogenesis the exact mechanisms of HCC
      development is not understood. Various causes initiate a multistep process of
      several steps: chronic liver injury, chronic inflammation, cell death,
      regeneration, cirrhosis, DNA damage, dysplasia and HCC. Molecular changes cannot
      be used for risk assessment of patients with liver cirrhosis or liver cell
      dysplasia. They are not helpful for problems in differential diagnosis between
      dysplasia and HCC.

PMID- 18035687
TI  - [Epigenetic inactivation of the WNT antagonist SFRP1 in breast cancer].
AB  - The WNT signalling pathway plays a central role during embryonic development of
      multi-cellular organisms, especially for the temporal and spatial specification
      of organs (e.g. WNT4 in kidney development), a process called pattern formation.
      Interestingly, genes of the WNT pathway are deregulated in a variety of solid
      tumours, being considerably up- or down-regulated compared to their expression in
      the corresponding normal tissue. Some members like WNT1 have demonstrated
      oncogenic properties in animal models. The SFRP1 gene on chromosome 8 p12 is a
      negative regulator of the WNT pathway. SFRP1 protein is supposed to bind WNT1
      molecules thereby inhibiting the activation of frizzled receptors and the WNT
      pathway. Characterising an SFRP1-specific antibody we could show that loss of
      SFRP1 is an extremely common event in breast cancer, i.e. SFRP1 was considerably
      down-regulated in 73% (n = 1967) of analysed invasive breast cancers. SFRP1 loss
      is associated with unfavourable prognosis in early breast cancer (pT1 tumours).
      To analyse the cause of SFRP1 inactivation in breast cancer we performed a
      parallel expression and promoter methylation analysis in human breast cancer and
      tumour cell lines. RT-PCR techniques and methylation-specific PCR (MSP) were
      applied. All tumorigenic cell lines analysed exhibited complete promoter
      methylation and did not express detectable amounts of SFRP1 mRNA. SFRP1
      expression could be restored in these cell lines after treatment with 5-Aza-2'
      deoxycytidine, a demethylating agent. Human primary breast cancer was methylated
      in nearly 75% of cases. Our results indicate that epigenetic inactivation by
      methylation is the predominant mechanism of SFRP1 gene silencing in breast
      cancer.

PMID- 18035688
TI  - [mRNA expression analysis of metastatic markers in clear-cell renal cell
      carcinoma].
AB  - Deregulated expression of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors
      of Metalloproteinases (TIMPs) is an important pre-requisite for metastatic
      processes in a variety of human tumor types including renal cell cancer. Own
      previous cDNA microarray studies demonstrated differential expression of several
      MMPs and TIMPs in normal renal tissue and renal cancer cell lines. In order to
      analyze MMP/TIMP expression in primary clear-cell renal cell carcinoma (ccRCC)
      tissues we have determined the mRNA abundance of MMP-2, MMP-9, TIMP-1 and TIMP-2
      by RT-PCR in 29 ccRCC and 7 normal renal tissues. Compared to normal renal
      tissue, expression of MMP-2 and TIMP-2 was significantly reduced in 16 and 12 of
      29 ccRCCs, respectively. In contrast, MMP-9 expression was significantly
      increased in 11 of 29 ccRCCs. No difference was seen for TIMP-1 transcription
      levels. Because expression of the metastasis-associated CXCR4 chemokine receptor
      is increased and associated with poor tumour-specific survival in ccRCC we also
      compared MMP/TIMP and CXCR4 expression in the given tissue samples. Expression of
      TIMP-1 and TIMP-2 did not correlate with CXCR4 expression levels, whereas mRNA
      expression of MMP-2 and MMP-9 was significantly higher in tumours with strong
      CXCR4 expression (p = 0.04 and p = 0.01, respectively). These preliminary results
      suggest the involvement of CXCR4, MMP-2, and MMP-9 in renal cancer progression.

PMID- 18035689
TI  - [Adult stem cells regenerate the endocrine pankreas and normalize hyperglycaemia
      and insulin production in diabetic mice].
AB  - AIMS: The potential role of adult stem cells in the regeneration of beta cells in
      diabetes is still controversial. Although islet cell transplantation is currently
      the most pursued field of research, we have investigated the capacity of
      multipotent adult stem cells to correct hyperglycaemia in an experimental murine
      diabetes model. METHODS: Cloned stem cells were labelled with eGFP or transfected
      with a pTie2-RFP construct to show endothelial differentiation in vivo. The beta
      cell toxin alloxan was injected intravenously and all mice became hyperglycaemic
      (> 400 mg/dl) within two days and lost more than 90 % of their beta cell mass.
      Stem cells were then injected either directly into the pancreas or given
      systemically. RESULTS: Mice that received stem cell transplantation reached
      normal blood glucose levels within 14 days and the beta cell mass fully recovered
      within one month after treatment, regaining normal body weight soon after stem
      cell infusion. The host pancreas then dissociated and further analysed. The eGFP+
      donor cells did not express insulin and other endocrine markers, but showed a red
      fluorescence (RFP+) and CD31 expression instead, characteristics of endothelial
      cells after pTie2 activation. It was further shown that remaining (eGFP-) beta
      cells showed increased cell cycle activity. CONCLUSIONS: Endothelial
      differentiation from transplanted stem cells, induced by the environment of an
      injured pancreas, allows the regeneration of insulin production either through
      proliferation of still existing and residual beta cells in the islet or the
      recruitment and differentiation of beta cell progenitors mostly from the duct
      region via enhanced vasculogenesis and microcirculation.

PMID- 18035690
TI  - [Nuclear localization of heterochromatic regions varies in hyperplastic and
      preneoplastic lesions of the breast].
AB  - Previous molecular cytogenetic studies in breast cancer revealed numerous
      chromosomal changes and identified alterations involving the chromosomes 1 and 16
      as early incidents in mammary carcinogenesis. Since both chromosomes reveal
      pericentromeric heterochromatic areas, these chromosomal alterations might result
      from instable heterochromatin caused by DNA hypomethylation. In the present
      study, we investigated whether hyperplastic and neoplastic lesions of the breast
      differ regarding the distance between the heterochromatic areas of chromosomes 1
      and 16 within the nuclei. We hybridized differently fluorescence-labeled DNA
      samples specific for the heterochromatic regions of chromosomes 1 and 16 to
      formalin-fixed tissue sections. Histological classification of the lesions was
      supported by immunohistochemical staining using cytokeratin-specific antibodies.
      The methylation state of the heterochromatic regions was tested by staining with
      an antibody specific for methylated cytidin. Our results revealed an increased
      frequency of paired intranuclear signals specific for chromosomes 1 and 16 in
      neoplastic lesions (atypical ductal hyperplasia, ductal carcinoma in situ)
      compared to ductal hyperplasia and normal glandular epithelium. Staining with the
      methylation-specific antibody reavealed a weaker staining in neoplastic lesions
      compared to hyperplastic lesions and normal cells. We conclude that atypic ductal
      hyperplasia represents the histomorphological equivalent for the beginning of
      tumor genome evolution that progresses in ductal carcinoma in situ and
      infiltrating carcinoma.

PMID- 18035691
TI  - [Detection of high-risk human papillomavirus (HPV) E6 and E7 oncogene transcripts
      increases the specificity of the detection of a cervical intraepithelial
      neoplasia (CIN)].
AB  - AIMS: The oncogenic potential of the high-risk human papillomavirus (HR-HPV)
      genotypes depends on the expression of the viral oncogenes E6 and E7. Thus, the
      detection of these transcripts could serve as a factor in the evaluation of a
      woman's risk of development of cervical intraepithelial neoplasia (CIN). METHODS:
      A nested RT-PCR assay for the detection of E6/E7 oncogene transcripts of all
      known HR-HPV genotypes was established. Cervical scrapes of 779 HR-HPV-DNA
      positive women exhibiting all grades of CIN were examined. RESULTS: Spliced E6/E7
      oncogene transcripts of all the HR-HPVs were detected in numerous samples. In 459
      cases with agreement between the cytologic and histologic findings, the
      prevalence increased with lesion severity: CIN 0, 18%; CIN I, 58%; CIN II, 77%;
      CIN III, 84%. While sensitivity and negative predictive value of HR-HPV DNA
      positivity for the detection of a CIN lesion were significantly (p < 0.0001)
      higher than those of E6/E7 mRNA positivity (90.3% vs. 65.5% and 93% vs. 83.1%),
      the opposite was true for the specificity and positive predictive value (72.8 %
      vs. 95.2%) and 65.1% vs. 88.5%, p < 0.0001). Preliminary follow-up data in 120
      initially HPV-16 DNA-positive women revealed the development, persistence or
      progression of a CIN lesion in 33% (8/24) of HR-HPV DNA-positive and E6/E7 mRNA
      negative women, compared to 93% (66/71, p < 0.0001) in women in whom
      transcriptional activity of the E6/E7 oncogenes was detectable. CONCLUSIONS:
      Besides the identification of HPV DNA, the detection of HR-HPV E6/E7 oncogene
      transcripts may serve as a valuable tool in increasing the specificity of HPV
      testing.

PMID- 18035692
TI  - [Expression of early placenta insulin-like growth factor (EPIL) in breast cancer
      cells provides an autocrine loop with enhancement of predominantly HER-2-related
      invasivity].
AB  - AIMS: Recently, we were able to show that the expression of early placenta
      insulin like growth factor (EPIL) is expressed by highly motile HER-2-positive
      breast cancer cells in vitro (Brandt et al., Cancer Res. 2002) in Paget cells in
      vivo and indicates a poor clinical prognosis, irrespectively of other prognostic
      factors. METHODS: In order to demonstrate the interplay between HER-2 and Epil we
      established a cellular model for high simultaneous Epil and HER-2 expression. The
      HER-2-positive breast cancer cell line SKBR3 was modified with an EPIL expression
      vector. In addition, an assay for the knockdown of EPIL-expression via siRNA was
      established. Erk1/2 expression was measured via Western Blot. The phenotype of
      the viable cells was determined by laser scan microscopy. RESULTS: Epil
      overexpression in SKBR3 cells resulted in fast and frequent protrusion formation
      of the cells shown by laser scan microscopy. The cells were further characterized
      by a significantly increased invasiveness, which could be reversed by Epil
      specific siRNA treatment. Increased invasiveness and morphological changes were
      associated with a decreased erk1/2 phosphorylation. CONCLUSIONS: These data
      further supports the assumption that EPIL might provide an autocrine loop in HER
      2-positive breast cancer cells that enforce metastasis, conceivably escape from
      adjuvant therapy and in consequence poor clinical outcome. A tight interaction
      between HER-2 and EPIL in invasive breast cancer cells is therefore likely. The
      exact mechanims remain to be elucidated.

PMID- 18035693
TI  - [Bootstrapping algorithm approach reveals inherent regulatory pattern in 550
      invasive breast cancer cases: CK5/6/CK14 and CK8/18/CK19 builds an antagonistic
      set].
AB  - All the preliminary observations on a lot of marker sets defining different
      stages in the tumor development are building a framework of work hypothesis which
      can be verified in characterising large pools of histological uniform rated
      paraffin probes. We developed a bootstrapping algorithm based on correlation
      measures to uncover regulatory patterns of immunohistochemical characterized
      tissue arrays with 550 invasive breast cancer cases. The algorithm is implemented
      in 'S' a computer language used to model mathematical solutions. Focussing on the
      Cytokeratins versus a set of prominent markers in breast cancer differentiation
      it will be obvious that markers which are known to appear in early (progenitor)
      forms conform to CK5/6 and CK14 while others associated with late stages conform
      to CK8/18 and CK19. Markers examined are among others EGFR, EMA, erb-B2,
      Vimentin, p53, ER and PR. The developed approach is an elegant and complete
      procedure to reveal the real regulatory patterns which are enclosed in a certain
      experimental design. The statistical significance of the results calculated by
      our algorithm is generally high and in the presented experimental design smaller
      than 0.6 * 10E-6.

PMID- 18035694
TI  - [Study of efficiancy of teleconsultation: the Telepathology Consultation Service
      of the Professional Assoziation of German Pathologists for the screening program
      of breast carcinoma].
AB  - AIMS: In the autumn a German screening program was started for detecting breast
      cancer in the population of women fifty and above. For the first time in this
      program, quality assurance rules were established: All statements of the
      radiologists and pathologists have to be confirmed by a second opinion. This
      improvement in quality is combined with a delay in time and additional expence. A
      new Telepathology Consultation Service was developed based on the experiences of
      the Telepathology Consultation Center of the UICC to speed up the second opinion
      process. METHODS AND MATERIAL: The complete web-based service is operated under
      MS Windows 2003 Server, as web server the Internet Information Server, and the
      SQL-Server (both Microsoft) as the database. The websites, forms and control
      mechanism have been coded in by ASP scripts and JavaScript. A study to evaluate
      the effectiveness of telepathological consultation in comparison to conventional
      consultation has been carried out. Pathologists of the Professional Association
      of German Pathologists took part as well as requesting pathologists and as
      consultants for other participants. RESULTS AND CONCLUSION: The quality of
      telepathological diagnosis was comparable to the conventional diagnosis.
      Telepathology allows a faster respond of 1 to 2 day (conventional postal delay).
      The time to prepare a telepathology request is about twice as conventional. This
      ratio may be inverted by an interface between the Pathology Information System
      and the Telepathology Server and the use of virtual microscopy. The Telepathology
      Consultation Service of the Professional Association of German Pathologists is a
      fast and effective German-language, internet-based service for obtaining a second
      opinion.

PMID- 18035695
TI  - [Evaluation of potential target genes of the 6p22.3-amplicon in urinary bladder
      cancer].
AB  - Amplification of 6 p22.3 is one of the most frequent chromosomal alterations in
      high grade and invasive urinary bladder cancer. In order to determine
      amplification levels of all known genes inside the 1.6 kb core amplicon, we
      constructed a small tissue microarray (TMA) from 9 primary bladder cancers and 4
      bladder cancer cell lines with known 6p22 amplification, and analyzed it with a
      panel of 16 overlapping FISH probes constructed from bacterial artificial
      chromosomes (BACs). The highest amplification rates were observed for the
      transcription factor E2F3 and the adjacent gene NM_017774, the function of which
      is not known. For a more detailed analysis of these genes, additional large
      section analysis was done in 19 primary bladder cancers and 18 bladder cancer
      cell lines. It showed that E2F3 and NM 017774 were always coamplified, but
      amplification levels in terms of the number of gene copies were slightly higher
      (16-19 copies per nucleus) for E2F3 as compared to NM_017774 (13-15 gene copies).
      Our study demonstrates that E2F3 and NM_017774 are located on the top of the
      6p22.3 amplicon in bladder cancer. It remains to be studied which one of the two
      genes drives 6p22 amplification, or if both genes contribute jointly to the
      aggressive features of 6p22 amplified bladder cancers.

PMID- 18035696
TI  - [Promoter methylation and microsatellite mutation reveals the clonal relationship
      of multiple urothelial carcinomas with mutator phenotype].
AB  - AIMS: The clonality of multiple urothelial carcinomas (UC) is subject to debate
      and affects treatment. Evidence derived from X-chromosome mosaicism and patterns
      of molecular alterations supports both a mono- and polyclonal relationship. In
      contrast to most UC, tumours with the mutator phenotype have frequent mutations
      in repetitive sequences (MSI) and promoter methylation. The aim of this study was
      to investigate the clonality of multifocal UC with MSI. METHODS: We have screened
      400 UC for MSI and found it to occur in 1% of bladder and 15% of upper tract UC.
      Of these, 9 patients, whose tumours had MSI, developed or presented with multiple
      UC. A total of 32 UC (occurring over 0-6 years, 2-12 TCC per patient), 2 cases of
      CIS and 9 normal urothelial samples were screened for MSI at 17 loci and aberrant
      promoter methylation at 7 genes. RESULTS: In 8 of 9 patients, the pattern of
      microsatellite mutation and promoter methylation suggested that the multiple
      tumours had a clonal origin. Patterns of aberrant methylation in multiple tumours
      were more similar than microsatellite mutations, suggesting an earlier
      carcinogenic timing. MSI and promoter methylation were present in macroscopically
      normal urothelium from these patients. CONCLUSIONS: Aberrant promoter methylation
      occurs before microsatellite alteration in UC with mutator phenotype. The
      majority of recurrent UC with MSI are monoclonal in origin and macroscopically
      normal urothelium harbours multiple molecular abnormalities. Thus, at the time of
      apparently successful treatment, there is molecular evidence of residual tumour
      that subsequently develops into recurrent disease.

PMID- 18035697
TI  - [Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2
      action in MedB-1 mediastinal lymphoma line].
AB  - Primary mediastinal B-cell lymphoma (PMBL) is a well-defined subtype of diffuse
      large B-cell lymphoma. Molecular cytogenetics revealed frequent gains of 9 p24.
      JAK2, mapping in this region, is presently regarded as a candidate oncogene since
      expression profiling showed high JAK2 transcript levels and JAK2 was found to be
      constitutively phosphorylated in mediastinal B-cell lymphomas. We confirm that in
      the MedB-1 mediastinal B-cell line, harbouring a trisomy 9, JAK2 transcription is
      elevated and the product is highly phosphorylated. However, JAK2 is not over
      expressed at the protein level. On top, JAK2 protein turnover is even delayed.
      This unexpected finding coincides with a biallelic mutation of the SOCS-1 gene in
      this cell, which abrogates SOCS box function of the protein. Ectopic expression
      of wt-SOCS-1 in MedB-1 leads to growth arrest, dramatic reduction of phospho-JAK2
      and its downstream partner phospho-STAT5. We conclude that, in MedB-1, action of
      phospho-JAK2 is sustained due to defective SOCS-1. Hence, SOCS-1 qualifies as a
      novel tumor suppressor. Of note, the SOCS-1 mutations are also present in the
      parental tumor of MedB-1 and were detected in 9 of 20 PMBL.

PMID- 18035698
TI  - [Immunohistochemical and molecular characterization of systemic mastocytoses].
AB  - The WHO has published an updated classification of mastocytosis and the criteria
      for the diagnosis of systemic mastocytosis (SM). These include one major
      criterion, compact mast cell (MC) infiltrates in extracutaneous tissues, and four
      minor criteria, i.e. cytomorphologic atypia with spindling of MC (>25 %),
      detection of the activating somatic c-kit mutation D816 V in MC, aberrant
      expression of CD2 and/or CD25 on MC, and an elevated serum tryptase level (>20
      ng/ml). Systemic mastocytosis is diagnosed when the major plus one minor, or
      three minor criteria are fulfilled. In the present study, we have established
      methods for the detection of CD25 and the c-kit mutation D816V in paraffin
      embedded bone marrow trephine biopsy specimen of 57 patients with various
      subtypes of mastocytoses and 239 controls. While MCs in almost all patients with
      SM (55/57) expressed CD25, only 2/239 of the control samples contained CD25
      positive MCs. With newly designed molecular pathological methods, c-kit codon 816
      mutations were detected by "peptide nucleic acid" (PNA)-mediated PCR-clamping
      and/or analysis of microdissected MC in 52/57 cases with SM. All cases with
      detectable c-kit mutations also contained CD25-positive MC. The c-kit mutation
      D816 V was also detected in microdissected cells of associated hematologic
      neoplasias in 6/15 cases. With the methods established for the investigation of
      paraffine-embedded tissues, the pathologist plays a central role in the diagnosis
      of SM.

PMID- 18035700
TI  - [Anaplastic large cell lymphomas lack the expression of T-cell receptor
      molecules].
AB  - Anaplastic large cell lymphoma (ALCL) designates a heterogeneous group of CD30+
      (systemic or primary cutaneous) peripheral T-cell lymphomas (PTCLs). A subgroup
      of systemic ALCL is transformed by anaplastic lymphoma kinase (ALK). We compared
      46 ALCL with 22 PTCLs in terms of T-cell receptor (TCR) rearrangements,
      expression of TCRs and TCR-associated molecules [CD3, ZAP-70 (zeta-associated
      protein 70)]. Despite their frequent clonal rearrangement for TCRbeta, only 4% of
      ALCLs expressed TCRbeta protein, whereas TCRs were detected in 86% of PTCLs.
      Moreover, both TCRbeta+ ALCLs lacked CD3 and ZAP-70 (ie, molecules indispensable
      for the transduction of cognate TCR signals). Defective expression of TCRs is a
      common characteristic of all types of ALCL, which may contribute to the
      dysregulation of intracellular signaling pathways controlling T-cell activation
      and survival. This molecular hallmark of ALCL is analogous to defective
      immunoglobulin expression distinguishing Hodgkin lymphoma from other B-cell
      lymphomas.

PMID- 18035699
TI  - [Insulin-like growth factor (IGF)-II in human hepatocarcinogenesis--a potential
      therapeutic target?].
AB  - Several studies have examined the expression profiles of human hepatocellular
      carcinomas (HCCs) using high density microarray technology, but subtyping with
      potential mechanistic and therapeutic impact has not been achieved so far. Here
      we have analysed the expression pattern of human HCCs and HCC cell lines in
      comparison to normal liver. A characteristic of one group of HCCs and all HCC
      cell lines was overexpression of insulin-like growth factor (IGF)-II. Moreover,
      IGF-II expression was mutually exclusive to induction of several IFN-related
      genes. In vitro, treatment of HCC cells with IFNgamma leads to a strong reduction
      of IGF-II expression. Equally, specific reduction of IGF-II was achieved using
      RNAinterference in HCC cells. Therefore, IGF-II may represent an excellent target
      for IFNgamma-treatment and specific siRNA-mediated therapeutic intervention.

PMID- 18035701
TI  - [Coronary arterial perforation during endovascular intervention].
AB  - The paper deals with the timely detection and treatment of a menacing
      complication during endovascular interventions, such as coronary arterial
      perforation. It describes the causes of perforations, their classification, and
      an algorithm of actions to eliminate this complication. A clinical example
      demonstrates the sequence of operations for the detection and correction of
      coronary arterial perforation.

PMID- 18035702
TI  - [Current issues in x-ray diagnosis of cervical osteochondrosis in the course of
      medical rehabilitation].
AB  - The results of studying 500 patients with neurological manifestations of cervical
      osteochondrosis are presented. All the patients underwent in the vertical
      position X-ray studies in the frontal, lateral, and axial projections, as well as
      functional spondylography. The development of radiological signs in patients with
      cervical osteochondrosis and that of the morphological and functional signs of
      degenerative and dystrophic changes in the cervical spine are discussed.
      Comprehensive evaluation of osteochondrosis used criteria for cervical motor
      disorders and impaired disk amortizing and spinal fixing functions. The degree of
      intradural space compression was also estimated. The studies have yielded a new
      classification of osteochondrosis and recommendations at the stages of medical
      rehabilitation.

PMID- 18035703
TI  - [Long-term results of sequelae after ligation of the ascending branch of the left
      uterine artery during cesarean section].

PMID- 18035704
TI  - [Current progress trends in and prospects for radiation diagnosis].
AB  - The paper describes the developmental stages of radiological diagnosis from the
      solution of health problems, by studying the substrate "shadow", to the
      possibility of investigating superfine changes at the level of molecular
      radiology. A number of lines forming a service in relation to the country's
      economic, technological, and social development are identified. Priority
      strategic tasks are defined.

PMID- 18035705
TI  - [Radiation studies in the diagnosis of changes in the stump of the hip and shin
      after amputation for mine explosion injury].

PMID- 18035706
TI  - [Radiation studies in patients with lymphoproliferative diseases].

PMID- 18035707
TI  - [Delayed allergy-like reactions of iodine-containing Xray agents. Is there such a
      clinical problem?].

PMID- 18035708
TI  - [Water immersion as an anti-g protection for pilot. Pro et contra].
AB  - In the period of 1988 - 1990 the ZVEZDA Aerospace medicine Department fulfilled
      comprehensive physiological investigations in order to assess the prospects for
      water immersion as an anti-g gear for pilots of high-maneuver aircraft. Both dry
      and open water immersion methods were used. More than 150 centrifuge runs were
      conducted to define limits for the acceleration value and time of 9-g tolerance.
      Volunteered subjects in the pilot's posture were inclined at 35 degrees and 55
      degrees to the total inertial force vector. The obvious subjective discomfort
      felt during acceleration and absence of clinical aftereffect were qualified as a
      positive outcome. The subjects were ready for repeated runs even after a very
      brief repose. The main impediment to the professional anti-g use of immersion is
      visual disorders which in this case are not predictors of coming loss of
      consciousness and attributed to alterations in regional hemodynamics. The authors
      assert that there is a good reason to continue search for implementation of the
      immersion principle in g-protection of pilots to reduce the rate of professional
      pathologies and to intensify flights.

PMID- 18035709
TI  - [Possibility to predict cosmonauts' orthostatic tolerance following short-and
      long-term space flights].
AB  - According to the analysis of the data of active and passive orthostatic tolerance
      (OST) testing before and after 67 short- (SSF) and 53 long-term (LSF) space
      flights OST declined in all the cosmonauts regardless of flight length. Active
      testing on R+1 after SSF (7 to 25 d) and LSF (49 to 438 d) attested OST loss by
      33% and 48%, respectively. Full OST recovery following SSF and LSF was observed
      in a week and 1.5-2 months, respectively. A correlation was established (r =
      0.81) between the post-flight OST loss and pre-flight baseline value. Depending
      on whether the pre-flight OST value was very good, good or satisfactory, its loss
      on R+1 after LSF can make up 20-30%, 30-50% and 55-65%, respectively.
      Consequently, data of preflight OST testing can be used for prediction of its
      decline post normal space flight.

PMID- 18035710
TI  - [Diagnostic potential of the lower-body negative pressure test in medical
      monitoring during extended space flights].
AB  - To put into service the diagnostic and prognostic capabilities of the lower body
      negative pressure test (LBNP) during extended space flights, cardiovascular
      reactions associated with various levels of test tolerance were analyzed and
      compared. The article gives account of 60 tests performed by 44 cosmonauts 33 to
      53 years of age during 59- to 415-d flights. In 36 tests tolerance was good and
      in 24 - satisfactory. Medical evaluation was fulfilled using GaMMa-1M, an onboard
      multifunctional medical monitoring system. Dynamics of ECG, blood pressure,
      stroke and minute volumes, pulse filling, and vertebral-basilar tone exhibited
      some specific traits that mirrored LBNP tolerance. Established were
      diagnostically implicative values in the course of pressure drop. Evidence was
      obtained that during the test and ensuing data analysis consideration should be
      given as to the span of changes of each parameter, so the time of their
      initiation, and dynamics.

PMID- 18035711
TI  - [Evaluation of the effectiveness of interpersonal interactions in an experiment
      with long-term isolation].
AB  - A computerized Homeostat test was used in three chamber experiments to study
      dynamics of cooperative fulfillment of homeostatic tasks and construct a
      mathematical equation thereupon. Personal input of each group member in goal
      achievement was assessed and compared at the end of isolation period.

PMID- 18035712
TI  - [The effect of sensory stimuli of varying modality on the human body functioning
      and indices of tense muscular activity].
AB  - The work had a purpose to study benefits of aromatic blends of tonic and relaxing
      essences and functional music on some of the psychophysiological properties of
      the human functional state and motor activeity. Participants were 30 sprinters
      (18-22 y.o. males) having the first-class and master ranks. The
      psychophysiological indices of the athletes' functional state were evaluated with
      the use of the "CAH" and Spilberger situational anxiety tests, calculated Cardeu
      vegetative index, time for simple motor reaction and reaction to a moving object.
      Motor activity was evaluated by top running speed determined with a photo
      electronic time-keeper and by duration of pedaling on bicycle ergometer at
      maximal power. The running step parameters were recorded with electropodography.
      It was shown that the positive effect of the aromatic essence blends and
      functional music on motor activity developed fairly rapidly but did not last
      long. The article discusses features and possible ways the aromatic blends and
      music effect human organism.

PMID- 18035713
TI  - [Radiation safety provisions in a piloted mission to Mars based on calculated
      risks of overdose behind shielding].
AB  - The article deals with the prime sources of radiation hazard in a mission to
      Mars, compares the radiation risk values in flight and over the life span with
      consideration for various shielding thicknesses in habitable compartments and
      radiation shelter, and estimates possible life shortening. Given the stochastic
      nature of solar cosmic rays effects in a two-year mission and probability of
      powerful solar proton events, calculated were not only the mean tissue-equivalent
      doses behind various thickness of the shelter but also probability of their
      violation, risks of immediate and delayed radiation consequences and conceivable
      approaches to risk mitigation.

PMID- 18035714
TI  - [Calculation of radiation loads onto cosmonauts during extravehicular activities
      on the International space station].
AB  - A geometrical spacesuit model was developed to assess shielding functions of the
      human body systems and organs. The shielding functions of specific points inside
      the spacesuit determined with the help of the geometric human body model were
      compared with the published data from experiments with the Russian Orlan-M
      spacesuit. Provided a good agreement of the results, shielding of specific organs
      and systems within the human body geometrical model were calculated. Periods of
      the ISS EVAs in the Russian spacesuits during 2001-2006 were analyzed to estimate
      the absorbed doses and quality factor for the body organs and systems. Methods
      for calculating the absorbed doses from the data of EVA dosimeters are proposed.

PMID- 18035715
TI  - [Greenhouse with a convex spherical planting surface as a prototype of space
      greenhouse and an instrument for studying the plant gravitropism].
AB  - IBMP has developed a technology and unit for cultivating self-opening crops on a
      convex planting surface illuminated by light-emitting diodes mounted on an
      external concentric panel ("Hemisphere"). The unit has a structure of two-member
      clinostat with semispherical plant growth chamber with a 600-mm diameter and a
      speed of from 1 to 10 revo about each axis; water potential in the root supply
      system is maintained at 1.0 +/- 0.45 KPa. Having the data of 1200 measurements in
      the growth chamber, PAR latitude and meridian gradients were determined which did
      not exceed 0.7 micromol/(m2 x s x cm) in the work area and differed from the
      radial gradient by order and, therefore, had a negligible contribution to the
      axial organs' deviation from the radial directions during laboratory tests.
      Maximal centrifugal acceleration was equal to 10(-10) of the acceleration of
      gravity and did not impact the gravitropic crop reactions in the growth chamber.
      Five 5-day tests with semidwarf wheat Triticum aestivum L., cult. Lada were
      performed in the "Hemisphere" growth chamber turned at different angles relative
      to the gravity vector. In immobile growth chamber plants inclination from the
      vertical was a function of the angle between the PAR gradient and vector and the
      gravity vector at the site of each seed. Crop rotation at 3 revo about the
      horizontal axis did not produce noteworthy plant inclination suggesting
      neutralization of the plant geotropic reactions. In all tests about 80% of the
      plants formed the first leaf and about 20% reached the coleoptiles phase.
      Morphometric differences in the tests were insignificant. On a balance, the tests
      showed that prototype of space greenhouse "Hemisphere" is fit to run laboratory
      investigations of the plant gravitropic reactions in both static and dynamic
      conditions.

PMID- 18035716
TI  - [The relationship between adaptation to hypoxia and the monoaminergic systems of
      the central nervous system].
AB  - The role of CNV monoaminergic systems (MAES) in development of residual
      adaptation was studies in Wistar rats with high and low resistance to hypoxia and
      varying adaptive potential. Adaptability to hypoxia was found to depend on
      initial resistance to the factor. Mobilization of the adaptive potential was
      reflective of specifics of the MAES mechanisms. In well-adapted animals the MA
      concentration was typically high with the desamination products either increased
      or decreased depending on individual sensitivity to hypoxia. In poorly adapted
      rats MA synthesis by the stress-suppressing systems was lowered which prevented
      the humoral effects resulting in the development of residual structural and
      functional adaptation.

PMID- 18035717
TI  - [Characteristics of the vegetative status in different clinical cases of
      vegetative dysfunction in young people].
AB  - Clinical-experimental observations of the vegetative nervous system in students
      with vegetative dysfunctions (VD) consisting of studying functional dynamics of
      the vegetative tone, reactivity, and regulation made it evident that each
      clinical case of VD is characterized by a certain vegetative status.
      Cardiovascular VD is distinguished by dominance of unnatural vagotropic
      reactivity on a background of initial sympathicotonia. Gastrointestinal VD was
      developed largely by individuals with unnatural sympathetic reactivity and
      initial vagotonia. Respiratory VD is characterized by increased vagotropic
      reactivity and inadequate vegetative regulation. These results permit
      differential rehabilitative correction of different clinical VD cases in students
      by selection of therapeutic factors depending on the type of vegetative
      disorders.

PMID- 18035718
TI  - [Free radical processes in aging, neurodegenerative diseases and other
      pathological states].
AB  - Literature data on the role of oxidative stress in the aging of an organism have
      been summarized. The connection of some parameters of free radical processes
      (intensity of generation of reactive oxygen species in mitochondria, oxidative
      modification to the mitochondrial DNA, the activity of desaturases participating
      in biosynthesis of polyunsaturated C20 and C22 fatty acids) with life expectancy
      has been demonstrated. Oxidative stress is one of pathogenetical events in many
      diseases, including various neurodegenerative disorders. The special attention is
      paid to oxidatively modified proteins as one of early and reliable indicators of
      tissue injury in freeradical pathology. Oxidative protein destruction plays an
      important role in etiology of such neurodegenerative diseases, as Alzheimer's and
      Parkinson's diseases. Oxidative stress and the aggregation of proteins connected
      with it are considered to be a pathogenetical part in the development of familial
      amyotrophic lateral sclerosis. Oxidatively modified proteins are also associated
      with the development of cataract. The increase of the oxidatized protein ratio
      with the age and in various pathologies is assessed as an early and specific
      parameter of oxidative stress.

PMID- 18035719
TI  - [The use of SNP markers for estimation of individual genetic predisposition to
      diabetes mellitus types 1 and 2].
AB  - Single nucleotide polymorphisms (SNPs) are now considered as the most perspective
      and convenient markers for research of genetic bases of multifactorial diseases.
      Fast development of technologies for exact screening of great volume of genetic
      information, construction of genomic maps of SNP-markers promotes development of
      innovative diagnostic systems on the basis of significant SNP for an estimation
      of individual genetic risk of development of various diseases. In this review the
      basic aspects of genetics of a diabetes of type 1 and 2 and an opportunity of use
      SNP as markers for an estimation of individual genetic predisposition to the
      given diseases are considered.

PMID- 18035720
TI  - [Nitric oxide. Potentiation of NO-dependent activation of soluble guanylate
      cyclase--(patho)physiological and pharmacotherapeutical significance].
AB  - The paper reviews the molecular mechanism underlying the physiological effects of
      nitric oxide (NO), the role of the signalling system: NO-soluble guanylate
      cyclase-cyclic 3',5'-guanosine monophosphate (cGMP) in the realization of NO
      action. The data concerning the basic chemical characteristics of guanylate
      cyclase, such as the subunits structure, isoforms, modem concepts of the
      catalytic and regulatory centers of the enzyme are presented. The role of
      guanylate cyclase heme and the enzyme itself in the realization of physiological
      effects of NO is demonstrated. The data concerning a new NO-independent,
      allosteric activator of soluble guanylate cyclase, YC-1 (benzyl indasol
      derivative) synergistically increased the NO-dependent activation of soluble
      guanylate cyclase are presented. The data on guanylate cyclase sites responsible
      for binding of the enzyme with YC-1 and possible molecular mechanism underlying
      the synergistic increase of NO-dependent activation of soluble guanylate cyclase
      by YC-1 are presented. New compounds of endogenous nature capable to potentiate
      and synergistically increase the activation of guanylate cyclase by NO-donors
      have been revealed and investigated. The important physiological,
      pharmacotherapeutical and pathophysiological significance of this new fact is
      discussed.

PMID- 18035721
TI  - [Identification of cytochromes P450 in the human liver microsomes by mass
      spectrometry].
AB  - Proteomic approaches have been used for detection and identification of
      cytochromes P450 from highly-purified membrane preparations of human liver. These
      included the protein separation by 2D- and/or 1D-electrophoresis and molecular
      scanning of a SDS-PAGE gel fragment in the range of 45-66 kD (this area
      corresponds molecular weights of cytochromes P450). The analysis of protein
      content was statistically evaluated by means of original 1D-ZOOMER software
      package which allowed to carry out processing of mass spectra mixture instead of
      individual mass spectra used by standard techniques. In the range of 45-66 kDa we
      identified 13 microsomal membrane proteins including 11 cytochromes P450, namely
      CYPs 1A2, 1B1, 2A6, 2E1, 2C8, 2C9, 2C10, 2D6, 3A4, 4A11, 4F2. The microsomal
      samples were characterized by the enzymatic assays using the marker substrates
      for CYP1A, 2B, 3A4, 2C and 2E1. The 7-methoxy- and 7-ethoxyresorufin-O-dealkylase
      activities (i.e. the marker activities for cytochromes P450 1A1/1A2,
      respectively) and the erythromycin-N-demethylase activity (i.e. the marker
      activity for cytochrome P450 3A4) are lowered in pathology compared to these
      activities in norm. At the same time the benzyloxyresorufin-O-debenzylase
      activity (which characterizes the total activity of CYP2B and CYP2C), the
      activities of CYP2E1 (methanol), 7-pentoxyresorufin-O-dealkylation (CYP2B), 7
      ethoxy- and 7-methoxycoumarin-O-dealkylases (CYP2B1) did not change. On the basis
      of the results obtained efficiency of a combination proteomic and biochemical
      analyses for inventory cytochromes P450 and revealing of their level expression
      is shown, and opportunities of mass spectrometry for a quantitative estimation of
      proteins are discussed.

PMID- 18035722
TI  - [The role of PAR1 in the protective action of activated protein C in the non
      immune mast cell activation].
AB  - Activated protein C (APC) regulates the functional activity of mast cells by
      reducing release of beta-hexosaminidase, the marker of mast cell degranulation.
      APC could modulate the cell secretion of both: the rest mast cells and the
      activated cells with degranulators, such as proteinase-activated receptor agonist
      peptide (PAR1-AP) and compound 48/80. PAR1 desensitization with thrombin
      abolishes the effect of low APC concentration (< or =1,5 nM) on beta
      hexosaminidase release by mast cells. APC, inactivated with
      phenilmethylsulfonilftoride (PMSF), did non mimic the enzyme action on mast
      cells. The duodenal proteinase, duodenase, activates the peritoneal mast cell via
      PAR1. APC abolishes the proinflammatory action of duodenase and PAR1-AP by means
      of reducing release of mast cell mediators. Pretreatment of mast cell with L-NAME
      abolished these APC effects. Thus, APC-induced decrease of mediator release could
      be attributed to NO generation by mast cells. Our data indicate that PAR1 takes
      part in the mechanism of regulatory anti-inflammatory APC action.

PMID- 18035723
TI  - [GABA metabolism and neuroactive amino acids in the rat brain in morphine
      withdrawal syndrome].
AB  - The changes in the neuroactive amino acid contents, GABA metabolism and TCA
      reactions have been studied in rat brain regions under experimental morphine
      withdrawal (MW). MW was developed by means of the cessation of morphine
      intraperitoneal injections 1 and 36 hours, 3 and 7 days after the course of
      morphine administration for 7 days. In cortex the significant increase in the
      contents of glutamate, glutamine, asparagine, and alanine was observed in remote
      terms of MW. In cerebellum MW led to the decrease in the levels of glutamine and
      asparagine and increase in glycine level, followed by the GABA-transaminase
      activation and the succinate dehydrogenase inhibition. In thalamus prolongation
      of MW caused to the further inhibition of the activities of the GABA-catabolising
      enzymes. The changes observed in the amino acids levels and the GABA shunt
      activity are likely to be explained by indirect adaptation of the brain regions
      differing in the opioid receptors contents to protracted morphine administration.

PMID- 18035724
TI  - [Antirheumatoid activity of methotrexate in phospholipid nanoparticles
      (Phosphogliv)].
AB  - The efficiency of methotrexate use in basic therapy of rheumatoid arthritis is
      limited because of risk of side effects and fast drug efflux from zone of joints
      as well. The new stabilized form of methotrexate was elaborated with phospholipid
      micelles as a carrier. The injective form of the preparation Phosphogliv was used
      for this purpose. Phosphogliv has recently been developed in the Institute of
      Biomedical Chemistry (Moscow), as the emulsion of 50 nm phospholipid
      nanoparticles stabilized by glycyrrhizic acid. The conditions of maximal
      methotrexate incorporation into the phospholipid nanoparticles were optimised
      under control of HPLC (60% of total methotrexate was associated with
      nanoparticles, with remaining drug being in free form in the water phase). Such
      preparation revealed higher therapeutic efficiency in experimental adjuvant
      arthritis in rats as compared with free methotrexate. The increase of
      antirheumatoid activity of the elaborated preparation may also be attributed to
      the influence of glycyrrhizic acid, possessing both antiinflammatory and immune
      properties. The possibility of clinical employment of a new methotrexate drug
      form for rheumatoid arthritis treatment is discussed.

PMID- 18035725
TI  - [Biochemical and photometric studies of modification of collagen structure under
      UV radiation].
AB  - The influence of UV irradiation (270-380 nm) on the biochemical, fluorescence and
      colorimetric properties of collagen was studied. The long-term UV irradiation
      (120 h) was accompanied by the increase of structural stability of collagen to
      specific and nonspecific proteolytic enzymes, by formation of new additional
      fluorophore-containing molecules, by the increase in quantity of carbonyl groups
      in the collagen and by strong changing of the distribution pattern of alkaline
      hydrolysis products during gel-chromatography. The coordinates of colour of the
      collagen films are also changed. These changes of collagen suggest that UV
      irradiation induces photomodification and photooxidation processes in collagen.

PMID- 18035726
TI  - [Glutathione system in erythrocytes and blood plasma in strokes and
      dyscirculatory encephalopathy].
AB  - In dyscirculatory encephalopathy and moderate ischemic stroke there are single
      changes of components of glutathione metabolism. In moderate and severe ischemic
      stroke frequent and considerable changes have been revealed. Changes in
      hemorrhagic stroke are also expressed. An increase of activities of glutathione
      peroxidase and glutathione transferase is the most typical, rarely the increase
      of glutathione reductase and GSH is observed. The increase of enzymes activity
      was absent at the delayed oneset of treatment (more than 3 days) and in severe
      cases patients who died later. Glutathione system is important in the tolerance
      to cerebral ischemia.

PMID- 18035727
TI  - [Expression of matrix metalloproteinase (MMP-2) and extracellular matrix
      metalloproteinases inducer (EMMPRIN) in benign and advanced breast cancer tissue
      samples].
AB  - Tumor cell derived matrix metalloproteinases are a family of enzymes associated
      with the tumor invasion and metastasis. Extracellular matrix metalloproteinases
      inducer (EMMPRIN) stimulates synthesis of gelatinase A (MMP-2) in peritoneal
      fibroblasts. In the present study the role of MMP-2 and EMMPRIN in the
      progression of breast cancer has been investigated. Gelatinase-A and EMMPRIN were
      analyzed in benign and stage II and stage III breast cancer tissue samples by
      gelatin zymography assay, immunoprecipation analysis and Western blot analysis
      with a monoclonal primary antibody specific for EMMPRIN. Our results showed
      overexpression of EMMPRIN in advanced stages of breast cancer tissues compared
      with benign tumor tissue samples. The expression of MMP-2, the active and latent
      forms of the enzyme increased with tumor progression from Stage II to Stage III
      of breast cancer and it was not expressed in benign tissues. The expression MMP-2
      correlates with tumor progression. This observation obviously indicates that
      EMMPRIN and MMP-2 are the major determinants of malignancy in cancers.

PMID- 18035728
TI  - [Antibiotic properties of the strains of the basidiomycete Lentinus edodes
      (Berk.) sing].
AB  - Antibiotic properties of the extracts from the fermentation broth and mycelium of
      15 strains of the edible and medicinal basidiomycete L. edodes were studied and
      it was shown that the extracts were active against grampositive and gramnegative
      bacteria, yeasts and mycelial fungi, including dermatophytes and phytopathogens.
      The strains differed by the set of the organisms susceptible to the action of the
      extracts. Strains of L. edodes combining marked antibiotic properties and high
      yields of water soluble polysaccharides were screened. The active compounds were
      detected by preparative TLC. Two of them were identified with UV- and mass
      spectrometry as lentinamycin B and erytadenine (lentinacin). Lentinamycin B was
      found to be the main component responsible for the antibiotic activity of the L.
      edodes strains.

PMID- 18035729
TI  - [Resistance epidemiology of gramnegative nonfermenting pathogens of nosocomial
      infections in intensive care units and surgical departments].
AB  - Etiological structure, patterns and antibiotic resistance mechanisms of
      gramnegative nonfermenting pathogens of nosocomial infections isolated from
      patients in intensive care units and surgical departments were investigated. One
      hundred thirty one clinical isolates, including 86 (65.6%) isolates of
      Pseudomonas aeruginosa and 45 (34.4%) isolates of Acinetobacter baumannii were
      tested. Carbapenems and cefoperazone/sulbactam showed the highest activity
      against the tested isolates. Eleven carbapenem resistant strains of P. aeruginosa
      were detected. The strains were found to possess genetic determinants of the VIM
      group encoding metal beta-lactamases.

PMID- 18035730
TI  - [Multicentre study of comparative efficacy of meropenem and combined regimens for
      empirical antibacterial therapy of severe nosocomial infections: results of
      clinical and pharmacoeconomic analysis].
AB  - Adequacy and effectiveness of empirical antibacterial therapy of severe
      nosocomial infections with meropenem vs. combined regimens of antibacterial
      therapy were investigated and the ratio of the cost and effectiveness of the
      compared regimens was evaluated. A prospective, randomized, open, comparative
      study of two initiative regimens of empirical antibacterial therapy of severe
      nosocomial infections was performed: meropenem in a daily dose of 1.5-3 g and the
      standard regimen with the use of betalactams and fluoroquinolones in combination
      with aminoglycosides and/or metronidazole. Patients with recorded diagnosis of
      nosocomial pneumonia (including the ventilator-associated one) or abdominal
      infection with the signs of severe sepsis and severity of APACHE II > 14 were
      enrolled. The patients were stratified into 2 groups subject to the disease
      severity, i.e. APACHE II 15-20 and APACHE II 21-25. One hundred thirty five out
      of 166 patients with recorded nosocomial infection were included into the final
      estimate of the therapy adequacy and effectiveness (Protocol Analysis): 62
      patients were treated with meropenem and in the treatment of 73 patients the
      standard antibacterial therapy was used. In the group of the patients treated
      with meropenem there were stated significantly higher clinical effectiveness
      (recovery in 80.6% of the patients vs. the control of 46.6%, p < 0.01) and
      pathogen eradication (89.6 and 48.1% respectively, p < 0.01). The difference in
      the clinical and bacteriological effectiveness of meropenem and the standard
      therapy was more evident in the subgroups of more severe patients (APACHE > 20).
      With the use of meropenem the probability of recovery from nosocomial infection
      was significantly higher (RR 1.73-1.94, p < 0.001) vs. the control. Meropenem
      provided significantly higher eradication of the pathogens: P. aeruginosa (88 and
      40% respectively, p = 0.007), E. coli (100 and 46.7%, p = 0.003), Acinetobacter
      spp. (90.9 and 40%, p = 0.02). The antibacterial therapy with the use of
      meropenem was assessed as adequate in 51 out of 56 patients (91.1%), that was 3
      times as frequent as with the use of the standard antibacterial therapy (33.9%).
      The cost-effectiveness coefficient with the use of meropenem was 2.2 times lower
      vs. the control. Therefore, the empirical therapy of severe nosocomial infections
      with meropenem proved to be more adequate and from the economic viewpoint more
      advantageous vs. the standard combined regimens of antibacterial therapy, that
      was evident from significantly higher clinical and bacteriological efficacy of
      the treatment and decrease of the terms of the patients hospitalization in
      intensive care units (on the average by 5 days).

PMID- 18035731
TI  - [Clinical and bacteriological efficacy and tolerability of meropenem in the
      treatment of bronchopulmonary affections in children with mucoviscidosis].
AB  - Meropenem (in combination with amikacin) was used in the treatment of children
      and adolescents with mucoviscidosis and severe exacerbation of bronchopulmonary
      affections. The drug showed satisfactory clinical and moderate bacteriological
      effects (48.3%) as dependent on the severity and duration of the disease and the
      microbial flora. Meropenem was well tolerated: no side effects were observed
      during the treatment, whereas it was used in high doses (60-105 mg/kg daily).

PMID- 18035732
TI  - [Problems of screening novel antituberculosis antibiotics. 3. New data on
      mechanism of action of antituberculosis agents].

PMID- 18035734
TI  - [A study of applied microanatomy by endoscope-assisted via retrolabyrinthine
      approach].
AB  - OBJECTIVE: To study the microanatomy by endoscope-assisted via retrolabyrinthine
      approach. METHOD: Nineteen cadaveric heads fixed with formalin were dissected in
      our study. The data that endoscope could be extent and the distance between the
      important point were measured. By simulated the retrolabyrinthine approach,
      endoscope was placed to observe the nerves and vessels, the distance between
      nerves and the central point of the anterior edge of sigmoid sinus were measured.
      RESULT: The distance from the inferior margin of petrous ridge to the upper bound
      of endolymphatic sac was (9.93+/-1.52)mm; and from superior margin of petrous
      ridge to the inferior margin common bony crus was (4.64+/-0.91)mm;and from the
      intersection of posterior semicircular canal to the anterior wall of sigmoid was
      (7.85+/-1.47)mm on the left, and (5.69+/-1.68)mm on the right. The distance from
      inferior margin common bony crus to the anterior wall of sigmoid was (13.9+/
      1.71)mm on the left, and (11.31+/-2.03)mm on the right. The trochlear nerve and
      abducent nerve could be observed under endoscope. The relationship between the
      trigeminal nerve, acoustic nerve and the vessels could be identified clearly. The
      distance from the central point of the anterior edge of sigmoid to the roots of
      the trigeminal nerve, facial nerve, vestibulocochlear nerve and glossopharyngeal
      nerve were (29.88+/-2.77) mm, (32.04+/-2.04) mm, (29.17+/-1.65) mm, (35.49+/
      1.53) mm respectively. CONCLUSION: The visual field of the cerebellopontine angle
      appear wider by the endoscope assisted retrolabyrinthine approach. Nerves,
      vessel, internal acoustic pore, jugular foramen region can be clearly seen. Some
      minimal invasive surgery can be done by this approach.

PMID- 18035733
TI  - [Differential diagnosis between vertigo of posterior circulation ischemia and
      migrainous vertigo].
AB  - OBJECTIVE: To analyze two groups of patients with migrainous vertigo (MV )and
      vertigo resulting from posterior circulation ischemia (PCIV) and investigate the
      differential diagnosis between them. METHOD: There were 60 patients with MV and
      64 patients with PCIV. Clinical tests include high risk factors of posterior
      circulation ischemia (PCI), cerebral MRI, ocular motion and high stimulating rate
      ABR. RESULT: Among 64 patients with PCIV, 29 had abnormal blood pressure and 14
      had abnormal blood fat and/or pathoglycemia; 37 had abnormality in cervical
      vascular ultrasound; 14 suffered from amaurosis or dizziness upon fast getting
      up. Twenty two had abnormal high stimulating rate ABR and 4 had cerebral lacunar
      infarction in MRI. As for 60 patients with MV, 45 suffered from motion sickness;
      20 were sensitive to motion; 32 had photophobia and (or) phonophobia; 45 had
      migraine; 16 had abnormal ocular motion function; 3 had abnormal cerebral MRI and
      40 had abnormal results in high stimulating rate ABR. The percentage of abnormal
      high stimulating rate ABR in MV and PCIV were 53% (22/42) and 67% (40/60)
      respectively. CONCLUSION: The mean age of MV is younger than that of PCIV. Female
      is more prone to MV than male (2.75 : 1. 00); the sex difference in PCIV is
      lesser (1.46 : 1.00). Motion sickness, motion sensitivity, photophobia and (or)
      phonophobia are principal differential highlights to MV. The major
      characteristics of PCIV include abnormal blood pressure, abnormal blood fat,
      pathoglycemia and arteriosclerosis. Vestibular function tests could not serve as
      a differential point; Cerebral MRI might be helpful to differential diagnosis.
      The results of high stimulating rate ABR is not a differential point between PCIV
      and MV, but it might play a role in differentiating other kinds of vertigo.

PMID- 18035735
TI  - [The normal values of multiple-frequency tympanometry in normal newborns].
AB  - OBJECTIVE: To discuss the multiple-frequency probe tones tympanograms and the
      normal ranges of admittance, susceptance and conductance in normal newborns.
      METHOD: Tympanometries with 226 Hz, 678 Hz and 1000 Hz probe tones were obtained
      from newborn infants with normal TEOAE and DPOAE(55 infants, 110 ears), analysed
      multiple-frequency prone tones tympanograms and values of admittance, susceptance
      and conductance by using GSI-33 middle ear analyzer. RESULT: 226 Hz tympanograms
      for admittance, susceptance and conductance main were W-shaped, the percentages
      were 90.0%, 99.1% and 85.5%. 678 Hz tympanograms for admittance, susceptance and
      conductance main were single-peaked, the percentages of single-peaked type were
      62.7%, 77.3% and 62.7%, and the percentages of W-shaped type were 34.6%, 20.9%
      and 31.8%, had a little three-peaked type. 1000 Hz tympanograms for admittance,
      susceptance and conductance main were single-peaked, and percentages were 96.4%,
      99.1% and 97.3%, and had a little W-shape type but no three-peaked type. There
      were significant differences between admittance and susceptance, susceptance and
      conductance in 226 Hz and 678 Hz probe tones tympanogram. There were significant
      differences between admittance and susceptance, susceptance and conductance,
      admittance and conductance in 1000 Hz probe tones tympanogram. CONCLUSION:
      Multiple-frequency probe tones tympanograms and the normal ranges of admittance,
      susceptance and conductance of normal newborn infants is obtained, and 1000 Hz
      probe tone tympanometry is a sensitive test for function of middle ear in newborn
      infants.

PMID- 18035736
TI  - [Report on the study of who ear and hearing disorders survey protocol in Guizhou
      province].
AB  - OBJECTIVE: To undertake a population-based survey on the prevalence, pathogenic
      factors and medical requirements of ear and hearing impairment. METHOD: Using the
      probability proportion to size (PPS) method, 6626 residents were investigated in
      30 clusters with the WHO protocol. RESULT: The prevalence of hearing impairment
      was 17.1% (the standardized rate: 17.6% in the whole country). Degrees of hearing
      impairment were mild (11.0%), moderate (4.2%), severe (1.4%), and profound
      (0.5%). Among them, male were 663(20.2%) and female were 468 (14.0%). The
      prevalence of hearing disability was 6.1% (the standardized rate: 6.5% in the
      whole country). The causes of hearing impairment were ear disorders (31.4%), non
      infectious (42. 5%), genetic condino (6.7%), infectious disease (0.4%) and
      undetermined cause (29.3%). 13.8% of person needed otology and/or audiology
      actions. 9.1% of person needed hearing aid. CONCLUSION: The prevalence of hearing
      impairment and hearing disability is higher than last twenty years and it can
      provide scientific data for drawing up precaution and control strategies on
      deafness for government.

PMID- 18035737
TI  - [Sequence analysis of OTOF gene in a Chinese pedigree with autosomal dominant
      auditory neuropathy].
AB  - OBJECTIVE: To investigate if the OTOF gene contributes to the non-syndromic
      hearing loss of a Chinese pedigree with dominantly inherited auditory neuropathy
      (AN). METHOD: The subjects included were 9 live individuals in an autosomal
      dominant AN pedigree, 3 sporadic AN patients and 3 normal-hearing controls.
      Genomic DNA was isolated from the peripheral leukocytes of the subjects using the
      Pure gene DNA Isolation Kits. Firstly, the whole coding sequence of OTOF gene of
      one family patient were PCR amplified using specific primers. Each fragment was
      purified and subsequently analyzed by direct sequencing in an Applied Biosystems
      3 730 automated DNA sequencer. The resultant sequence data were compared with the
      standard sequence to identify deafness-associated mutations. Other DNA samples
      were then screened for these mutations by PCR amplification and sequence
      analysis. RESULT: PCR amplifications were successfully conducted in all the
      subjects. Comparison of the resultant OTOF sequence in one family patient with
      the standard sequence identified 10 nucleotide variants which do not lead to
      amino acid change. These mutations were also detectable in other family
      individuals, 3 sporadic AN patients and 3 normal-hearing controls. CONCLUSION:
      The OTOF does not seem to contribute to the pathogenesis of this Chinese AN
      family, which suggest new gene(s) involvement.

PMID- 18035738
TI  - [Results with a new type ossicular prostheses mixed bone morphogenetic protein
      and hydroxyapatite].
AB  - OBJECTIVE: To evaluate the results in patients who had ossicular chain
      reconstruction with a new type ossicular prostheses mixed bone morphogenetic
      protein and hydroxyapatite. METHOD: Analyze The effect of ossiculoplasty were
      analyzed in 59 cases. Ossiculoplasty using HA-BMP prostheses was performed in 26
      ears,PORP was performed in 19 ears, TORP was performed in 7 ears. RESULT: The
      hearing success rate was 92.3% of 26 ears and no extrusion were found in HA-BMP
      group. There was a significant difference in mean postoperative air-bone gap
      between HA-BMP prostheses and autograft bone. CONCLUSION: The new type HA-BMP
      prostheses can provide stable hearing results with high success rate over time.

PMID- 18035739
TI  - [Imaging features and surgical approach of external auditory canal
      cholesteatoma].
AB  - OBJECTIVE: To define the clinical and imaging features of external auditory canal
      cholesteatoma (EACC) and determine the characteristics most important to its
      clinical management. METHOD: Seventeen cases (21 ears) of EACC were
      retrospectively reviewed. Clinical data were collected for the history,
      presentation, physical examination findings and CT scans. The surgical management
      approaches were reviewed. RESULT: Patients presented with otalgia (n = 21),
      otorrhea (n = 16), ear-canal stenosis (n = 11), facial nerve dysfunction (n = 4).
      CT scans showed a soft tissue mass with adjacent bone erosion (n =21). Middle ear
      and mastoid involvement (n = 9), facial canal erosion (n = 4), sigmoid sinus
      erosion (n = 1) and jugular bulb dehiscence (n = 1) were observed. EACC excision
      and canaloplasty through transcanal approaches were performed in 12 ears, while
      postauricular incision and canal wall down mastoidectomy were used in 9 ears.
      CONCLUSION: The possible causes of EACC and its possible extension may influence
      clinical management. Preoperative high-resolution temporal bone CT scans can be
      helpful in the diagnosis and management of EACC.

PMID- 18035740
TI  - [Isolated sphenoid sinus disease presented the primary symptom as headache or
      ocular disturbance].
AB  - OBJECTIVE: To improve the understanding of the symptoms and signs of isolated
      sphenoid sinus disease and decrease the occurrence of misdiagnoses. METHOD: The
      clinical manifestation and the advantage of endoscopic sinus surgery were
      analyzed in 22 cases of isolated sphenoid sinus disease. RESULT: Twelve cases had
      endoscopic sphenoidotomy, 7 cases had external ethmoidal sphenoidotomy, 3 cases
      had antibiotic, steroid and neurotrophic therapy. All of the patients were free
      of headache,improvement in vision and ocular motility after treatment. After 3 to
      6 months' follow up, 1 case recurred and symptom relieved after endoscopic sinus
      surgery. 1 case adenoid cystoid carcinoma underwent post operative radiotherapy
      without recurrence after 3 years follow up. CONCLUSION: Isolated sphenoid sinus
      disease presented the primary symptom as headache and/or ocular disturbance is
      prone to be misdiagnosed, application of CT, MRI and endoscopy improve its
      diagnosis and treatment standard. Endoscopic sinus surgery is the primary therapy
      for isolated sphenoid sinus disease.

PMID- 18035741
TI  - [Cholesteatoma of external auditory canal among 18 cases].
AB  - OBJECTIVE: To improve the diagnosis and treatment of the external auditory canal
      cholesteatoma (EACC). METHOD: The data of 18 patients caused by EACC were
      analysed retrospectively. RESULT: In all cases, the cholesteatomas were found in
      the external auditory canal and the mastoid cavity. CT scanning was using for
      definition the ranging of lesions and the timm management surgery was completed.
      There was no recurrence in 10-40 months follow-up. CONCLUSION: EACC is easily
      misdiagnosed as keratosis obturans (KO). The disease can progress to extensive
      mastoid destruction. CT of temporal bone and detailed history is necessary in the
      diagnosis. Early complete surgical treatment is the best method.

PMID- 18035742
TI  - [Construction of recombinant adenovirus and mediated reported gene expression in
      the guinea pig cochlea].
AB  - OBJECTIVE: To purify P0 protein from guinea pig's inner ear by preparative SDS
      PAGE and study the possible role it may play in the etiology of autoimmune inner
      ear disease. METHOD: A mixture of membraneous proteins of inner ear was separated
      by preparative SDS-PAGE. The corresponding band at 30kd was cut and electrically
      eluted. The protein collected was identified by analytical SDS-PAGE and Western
      blot assay. A group of 20 guinea pigs were immunized with P0 protein emulsified
      in complete Freund's adjuvant, another 10 guinea pigs were immunized with
      complete Freund 's adjuvant only as control. The guinea pigs' hearing thresholds,
      serum IgG level and morphological changes in the inner ear were investigated. The
      distribution of P0 protein in the cochlear was detected by immunohistochemical
      technique. RESULT: The purity of the protein was demonstrated by a single band at
      the 30 kD site in SDS-PAGE, which was identified as P0 protein by western blot
      analysis assay. About 17.5% P0-immunized guinea pigs showed increased hearing
      thresholds, elevated IgG level (F =6.48, P <0. 01), as well as a decreased number
      of spiral ganglion cells and inflammatory cell infiltration in the cochlear nerve
      region. The P0 protein is distributed in the cochlear nerve and spiral ganglion
      only. CONCLUSION: P0 protein from guinea pig's inner ear can be successfully
      purified by preparative SDS-PAGE and an animal model of experimental autoimmune
      inner ear disease induced by P0 protein is successfully established.

PMID- 18035743
TI  - [Animal model of experimental autoimmune inner ear disease induced by P0 protein
      purified from inner ear].
AB  - OBJECTIVE: To purify P0 protein from guinea pig's inner ear by preparative SDS
      PAGE and to study the possible role it may play in the etiology of autoimmune
      inner ear disease. METHOD: A mixture of membraneous proteins of inner ear was
      separated by preparative SDS-PAGE. The corresponding band at 30,000 was cut and
      electrically eluted. The protein collected was identified by analytical SDS-PAGE
      and Western blot assay. A group of 20 guinea pigs were immunized with P0 protein
      emulsified in complete Freunds adjuvant, another 10 guinea pigs were immunized
      with complete Freunds adjuvant only as control. The guinea pigs' hearing
      thresholds, serum IgG level and morphological changes in the inner ear were
      investigated. The distribution of P0 protein in the cochlear was detected by
      immunohistochemical technique. RESULT: The purity of the protein was demonstrated
      by a single band at the 30000 site in SDS-PAGE, which was identified as P0
      protein by western blot analysis assay. About 17.5% P0-immunized guinea pigs
      showed increased hearing thresholds, elevated IgG level (F = 6.48, P<0.01), as
      well as a decreased number of spiral ganglion cells and inflammatory cell
      infiltration in the cochlear nerve region. The P0 protein is distributed in the
      cochlear nerve and spiral ganglion only. CONCLUSION: P0 protein from guinea pigs
      in ner ear can be successfully purified by preparative SDS-PAGE and an animal
      model of experimental autoimmune inner ear disease induced by P0 protein was
      successfully established.

PMID- 18035744
TI  - The inflammatory response in cardiac surgery. An up-to-date overview with the
      emphasis on the role of heat shock proteins (HSPs) 60 and 70.
AB  - Cardiac surgical operations are associated with the development of a systemic
      inflammatory response syndrome (SIRS). In most cases, the inflammatory response
      is apparent only in its subclinical form. In some cases, however, it can become
      clinically manifest or even life-threatening. This review article presents some
      new data regarding its biological importance, along with an insight into the
      recently discovered role played by heat shock proteins 60 and 70.

PMID- 18035745
TI  - Contemporary all-ceramic materials, part-1.
AB  - Over the past 35 years, multiple types of all-ceramic materials have been
      introduced as an ideal alternative for metal-fused to ceramic. This review covers
      state-of-the-art development of all-ceramic systems in terms of history, material
      composition, fabrication technologies, and structural and strength properties.
      These materials are proved to be ideal in terms of mechanical properties and
      biocompatibility, making metal-free ceramic restorations a realistic clinical
      alternative for conventional metal-fused-to ceramic.

PMID- 18035746
TI  - Contemporary all-ceramic systems, part-2.
AB  - Current all-ceramic materials offer a accepted level of fracture resistance, fit
      and aesthetics. High fracture resistance recommends it to be a material to
      support fixed partial denture (FPD) in a stress bearing area with clinical
      success. This part of the present literature review covers the success rate,
      selection criteria of all ceramic systems, cementation technique, finishing and
      polishing. In vitro and in vivo studies of new high strength ceramics were well
      documented. Data suggest that single crowns in the anterior and posterior region
      are more predictable than bridges. Well-studied long-term success rate for FPDs
      are very limited.

PMID- 18035747
TI  - A pilot study of matrix metalloproteinases on the model of daunorubicin-induced
      cardiomyopathy in rabbits.
AB  - Matrix metalloproteinases (MMPs), activated by oxidative stress, play a key role
      during cardiac remodeling. In the present study we aimed to assess the role of
      MMPs in experimental cardiomyopathy induced by repeated 10-week administration of
      daunorubicin (3 mg/kg i.v.) to rabbits. In the daunorubicin group, the plasma
      cardiac troponin T levels (cTnT - a marker of myocardial necrosis) were
      significantly increased (p<0.05), commencing with the 8th administration compared
      with the controls. The amount of collagen (an estimate of fibrosis) was also
      significantly higher in the daunorubicin group (13.39 +/- 0.97 mg/g wet weight)
      compared to the control group (10.03 +/- 0.65 mg/g wet weight). In both groups,
      the LV MMP-activity was observed only in the gelatine substrate in the 70 kDa
      region (MMP-2), while no MMPs activities were detectable either in the casein or
      collagen containing zymograms. At the end of the experiment, the MMP-2 activity
      was slightly up-regulated (by 16 %) compared with the controls.

PMID- 18035748
TI  - Addition of rituximab significantly improves outcomes in patients with diffuse
      large B-cell lymphoma--a single-center, retrospective study.
AB  - CHOP chemotherapy has been used as a standard first-line treatment for diffuse
      large B-cell lymphoma since the 1970s. Phase III trials have shown that the
      addition of rituximab (R) to CHOP chemotherapy leads to significant improvements
      in response rate, progression-free survival and overall survival. This single
      center, retrospective study was performed to evaluate the role of the addition of
      R to chemotherapy (CHT) in a real-world clinical setting. Outcomes were assessed
      in 85 patients with newly diagnosed DLBCL treated with CHT alone (n=38) and R-CHT
      (n=47). Complete response (CR) rates were significantly higher after R-CHT than
      CHT (93 % vs. 73 %; p=0.02). The relapse rate was significantly higher after CHT
      compared with R-CHT (38 % versus 12 %; p=0.01). Progression-free survival was
      significantly extended by the addition of R (median not reached versus 26.1
      months; p=0.04). These data bring further support for rituximab-based
      immunochemotherapy as a standard first-line therapy for patients with DLBCL.

PMID- 18035749
TI  - Quality of life in adult patients treated with peripheral blood progenitor cell
      transplantation: the effect of selected psychosocial, demographics and health
      aspects on quality of life: a retrospective analysis.
AB  - AIM: this retrospective study analyses the effect of selected psychosocial,
      demographics and health aspects on quality of life (QoL) in adult patients
      treated with peripheral blood progenitor cell transplantation (PBPCT). PATIENTS
      AND METHODS: The total number of respondents treated with PBPCT between the years
      2001-2003 was 95. The return rate of QoL questionnaires was 72.1 % (71
      respondents). There were 100 % ratable QoL questionnaire. The average age of all
      respondents was 55.5 years old. The Czech version of an international generic
      European Quality of Life Questionnaire - Version EQ-5D was used. The effect of
      selected aspects on QoL of patients was determined by analysis of variance. The
      QoL questionnaires were evaluated with descriptive analysis. RESULTS: The above
      mentioned aspects proved statistically significant dependence of QoL (EQ-5D score
      - QoL dimensions, EQ-5D VAS - subjective health condition) on age, increasing
      number of associated diseases, religion and type of disease. The effect of other
      aspects on QoL was not proven statistically significant. The QoL in adult
      patients treated with PBPCT declines with increasing age and with the increasing
      number of associated diseases. People of faith have a higher level of QoL than
      non-believers. Patients with multiple myeloma treated with PBPCT have the most
      low QoL. CONCLUSION: The global QoL in an adult patients treated with PBPCT is on
      a good level.

PMID- 18035750
TI  - The effect of selected health, demographic and psychosocial aspects on quality of
      life in patients with peripheral arterial occlusive disease--a prospective
      analysis.
AB  - BACKGROUND: Peripheral arterial occlusive disease (PAOD) is a prevalent
      atherosclerotic disorder characterized by exertional limb pain, loss of limb, and
      a high mortality rate. Because of its chronic nature, it often has a negative
      impact on a patient quality of life (QoL). Aims. To evaluate the effect of
      selected health, demographic and psychosocial aspects on QoL in respondents with
      PAOD. PATIENTS AND METHODS: The study is a prospective and cross-sectional. It
      was carried out at the 2nd Department of Medicine of Charles University Hospital
      at the Faculty of Medicine in Hradec Kralove, Czech Republic. Forty two
      respondents with PAOD (28 male, 14 female) were evaluated. All the respondents
      had involvement of femoral and popliteal arterial circulation. The number of all
      respondents in accordance with Fontaine classification was as follows:
      intermittent claudication: stage IIa - 4, stage IIb (<200 m) - 16, stage IIb (<50
      m) - 9, chronic limb ischaemia: stage III - 6, stage IV - 7. The average age of
      all respondents was 65,4 years old (age range 45-79 years old). The study
      evaluates the effect of health aspects (stage of PAOD in accordance with Fontaine
      classification, diabetes mellitus, arterial hypertension, hyperlipidaemia,
      obesity, smoking), demographic (age, sex) and psychosocial aspects (level of
      education, marital status, religion) on QoL in respondents with PAOD. The Czech
      version of the International Generic European Quality of Life Questionnaire - EQ
      5D was used. RESULTS: The statistical evaluation presents statistically a
      significant dependence of QoL in respondents with PAOD on age (p < 0,01) and the
      stage of PAOD in accordance with the Fontaine classification (p < 0,01). The
      effect of other health, demographic and psychosocial aspects was statistically
      insignificant. CONCLUSION: The results had shown that with an increasing age and
      with a serious stage of PAOD in accordance with Fontaine classification, the QoL
      declines. The global QoL in respondents with PAOD is low.

PMID- 18035751
TI  - The influence of repeated blood withdrawals before surgery on clinical outcome.
AB  - The aim of this study was to find the influence of blood withdrawals and diet
      iron on elective surgery. Male Wistar rats (n=24) were divided: 1. group (SLD)
      ate standard laboratory diet (SLD), 2. group (FE) an iron enriched diet (FE) with
      one blood withdrawal after 9 weeks. 3. group (SLD-w) SLD and 4. group (FE-w) ate
      the FE diet; with 9 withdrawals once a week. The rats were sacrificed 18 hour
      after partial hepatectomy (PH) in the 10th week. Liver DNA synthesis (3H-thymidin
      - kBq/mg DNA) was performed. Serum hepcidin (pg/ml), iron concentration,
      respiratory burst of polymorfonucleares (RB, spontaneous; stimulated, %), count
      of blood cells were determined. FE-w had a higher (2.36+/-0.36) liver DNA
      synthesis after PH vs. SLD (1.21+/-0.49). Higher hemoglobin in erythrocytes (pg)
      was in FE-w and SLD-w vs. FE and SLD. PMN count in SLD-w, FE-w increased vs. SLD,
      FE. Hepcidin after PH decreased in SLD (78.0), FE (68.0), FE-w (97.0), but
      increased in SLD-w (217). Serum iron increased in SLD-w. RB after PH increased in
      FE-w (4.5; 47.6) vs. SLD (1.15; 29.1), FE (3.20;17.8), SLD-w (3.30;13.7).
      CONCLUSIONS: The iron diet with stimulation of haematopoesis by withdrawals
      improves an organism's condition expressed as better response to elective surgery
      and better PMN functions.

PMID- 18035752
TI  - Elevation of testosterone and reduction of transepidermal water loss by viewing a
      humorous film in elderly patients with atopic dermatitis.
AB  - The effect of viewing a humorous film on salivary testosterone levels and
      transepidermal water loss (TEWL) values on the back of the neck in 36 elderly
      healthy people (36 male, mean 70 years) and 36 elderly patients with atopic
      dermatitis (AD) (36 male, mean age 70 years) were studied. Salivary testosterone
      levels were decreased while TEWL values were increased in elderly patients with
      AD compared to those in elderly healthy people. Viewing a humorous film (The Best
      Bits of Mr. Bean, Universal studios, 1996) slightly, but significantly (P<0.05),
      elevated salivary testosterone levels and reduced TEWL values in elderly healthy
      people, while viewing a control non-humorous film (weather information) failed to
      do so. Similarly, but more pronouncedly, viewing a humorous film markedly
      elevated salivary testosterone levels and reduced TEWL values in elderly patients
      with AD, while viewing a control non-humorous film failed to do so. These finding
      indicate that viewing a humorous film may be useful in the study of testosterone
      and TEWL, and treatment for dry skin in elderly people with or without AD.

PMID- 18035753
TI  - Use of stabilometric platform and evaluation of methods for further measurements-
      a pilot study.
AB  - Posture in a still stance has been quantified by changes in the center of
      pressure (COP), in both anterior-posterior (A/P) and medial-lateral (M/L)
      directions and measured on a single force platform (Bertec PRO VEC 5.0). The
      purpose of this study was to estimate the variance in error and the intrasession
      test-retest reliability, and to determine which measures shall be taken for
      further measurements, especially with adults age 65 and older. We used two types
      of approximation for the reliability coefficient. Firstly, we used the equation
      according to Blahus (2) and secondly we used the Pearson's correlation
      coefficient for test-retest measurements. The findings allow us to say, among
      other things, that the tests of quiet standing Double Narrow Stance Eyes Open
      (DNSEO) and Double Narrow Stance Eyes Closed (DNSEC) are parallel, in the sense
      of parallel testing.

PMID- 18035754
TI  - Improvement in rabbit corneal cell suspension viability after freezing with
      Gingko Biloba extract.
AB  - We investigated whether the addition of Gingko Biloba extract (EGb 761) to rabbit
      corneal epithelial medium before cell freezing improved cell viability after
      freezing then thawing. After removal of corneas, they were treated with enzymes
      and the corneal epithelium was prepared as a single cell suspension in freezing
      media with or without EGb 761. After freezing for two weeks then thawing, a
      higher cell viability was found in the cornea cell suspensions which had been
      frozen pretreated with EGb 761 in the media. The improvement with corneal cell
      viability with EGb 761 pretreatment is postulated to be based on the antioxidant
      capacity of the plant extract.

PMID- 18035755
TI  - The pattern of acute myocardial infarction in people with opportunistic
      infections.
AB  - First comparative analysis for some hemocoagulation reactions, immune state of
      acute myocardial infarction has been done in two groups of patients - with
      mycoplasma infections and without one. Postinfarction complications in the groups
      were observed. Atherosclerotic plaques of the patients were also studied on a
      presence of mycoplasmas and a content of strontium and zinc. A tendency to a mild
      pattern of acute myocardial infarction was observed in patients with mycoplasma
      infections. The role of mycoplasmas in atherogenesis and acute myocardial
      infarction is discussed.

PMID- 18035756
TI  - Fasciola hepatica case with hemobilia.
AB  - Fasciola hepatica (FH) can lead to important hepatobiliary diseases. Here we
      present a case of hemobilia associated with biliary FH, which is quite a rare
      case. The 41-year-old patient, who underwent common bile duct exploration due to
      hemobilia, was found to have arterial bleeding associated with ulcer caused by a
      dead parasite in the common bile duct. Hemobilia is a very rare complication
      associated with FH. When searching for the cause of hemobilia, FH should be
      considered.

PMID- 18035757
TI  - Abrikossoff tumor of the larynx.
AB  - Case report about laryngeal localization of a granular cell tumor in a 38 years
      old female without recurrence over an observation period of two years.

PMID- 18035758
TI  - Mammography screening in women 40 to 49 years old.

PMID- 18035760
TI  - Pentalogy of Cantrell: a rare congenital abnormality.

PMID- 18035759
TI  - Herpes zoster in 2007: treatment and prevention.

PMID- 18035761
TI  - Hemangioblastoma without von Hippel-Lindau disease.

PMID- 18035762
TI  - Common skin pathology in LE prosthesis users.

PMID- 18035763
TI  - Improving care of the dying: what do the experts say?
AB  - The NIH State-of-the-Science Conference showed that much work still needs to be
      done to address the needs of patients at end of life. Whether young or old, such
      patients need and deserve the highest possible quality of life as they are dying.
      More randomized controlled studies need to be done, and appropriate new
      legislation needs to be passed. PAs can download the NIH State-of-the-Science
      Conference Statement at
      http://consensus.nih.gov/PREVIOUSSTATEMENTS.htm#EndOfLifeCare or obtain a written
      copy from the Office of Medical Applications of Research, National Institutes of
      Health, 6100 Executive Blvd, Rm 2B03, MSC 7523, Rockville, MD 20892; (800) 644
      2667.

PMID- 18035764
TI  - Fournier's gangrene: be alert for this medical emergency.

PMID- 18035765
TI  - Cardiac surgery: 1987 and 2007.

PMID- 18035766
TI  - What can I do about insomnia?

PMID- 18035767
TI  - What can I do about insomnia?

PMID- 18035768
TI  - Shortness of breath in a 27-year-old man.

PMID- 18035769
TI  - Case of the month. Pulmonary hamartoma.

PMID- 18035770
TI  - Leprosaria--a continuing social challenge.

PMID- 18035771
TI  - The role of thalidomide in the management of erythema nodosum leprosum.
AB  - Erythema nodosum leprosum (ENL, Type 2 reactions) complicates lepromatous and
      borderline lepromatous leprosy and can affect many organ systems, often with
      irreversible damage. The reactions commonly occur in the 2 years after starting
      treatment and often run a recurrent or chronic course, sometimes for many years.
      Even with WHO multi-drug therapy about 30% of LL patients experience ENL. We
      review drug management of ENL focussing on data from controlled trials and other
      studies. The treatment of ENL is difficult because high doses of steroids may be
      required for prolonged periods and do not always control the inflammation. The
      paradox of ENL is that it can be a life-threatening disorder and requires control
      with immunosuppression which may itself pose life-threatening risks for patients.
      Treatment with thalidomide provides an effective alternative to steroid therapy,
      gives better long-term control and avoids the adverse effects of prolonged
      steroid therapy. Controlled clinical trials have demonstrated that thalidomide
      rapidly controls ENL and is superior to aspirin and pentoxifylline. However,
      thalidomide is teratogenic when taken in early pregnancy and is unavailable in
      many leprosy endemic countries. We discuss the role of thalidomide in treating
      ENL, the complications encountered and risk reduction strategies that can be
      used. These include good patient selection and counselling, close supervision and
      adequate access to appropriate contraception. Further research is needed to
      improve the understanding and treatment of this severe and debilitating
      complication of leprosy. Topics for research include: i. The development of
      validated tools to measure the severity and/or activity of ENL. ii. A detailed
      assessment of the neurotoxic effects of thalidomide when used to treat ENL. iii.
      A well designed trial comparing thalidomide with prednisolone. iv. The
      development of a safe and effective alternative to both steroids and thalidomide.

PMID- 18035772
TI  - Adverse effects from multi-drug therapy in leprosy: a Brazilian study.
AB  - INTRODUCTION: The WHO MDT for leprosy treatment was officially introduced in
      Brazil in 1991 and comprises three drugs: dapsone, rifampicin and clofazimine.
      There are few good studies on the frequency of side-effects attributable to MDT
      in Brazil. METHODS: A retrospective and descriptive study carried out in a LCP in
      Vitoria, State of Espirito Santo, Brazil. A specific and detailed protocol about
      side-effects was prepared and filled in from the patient records. RESULTS: One
      hundred ninety four patients' records were analysed looking for side-effects
      attributable to MDT. Side-effects were attributed to at least one MDT component
      in 88 (45%) patients and 85 had side-effects due to dapsone, 24 due to rifampicin
      and 18 due to clofazimine. 185 episodes were identified. The suspected drug was
      stopped in 47 out of 88 episodes (24% patients); 46 had dapsone stopped, 5 had
      rifampicin stopped and no-one had clofazimine stopped. CONCLUSION: Side-effects
      attributed to MDT is more frequent than previously described, resulting in
      interruption of treatment in many patients.

PMID- 18035773
TI  - Circulating cytokine profiles in leprosy patients.
AB  - BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium
      leprae which is an obligate intracellular pathogen. It is characterised by a
      broad spectrum of clinical forms dictated by the patient's immune response to the
      organism. The tuberculoid pole has good cell mediated immunity to M. leprae, with
      few lesions and bacilli while the lepromatous pole has poor immunity coupled with
      extensive involvement and greater bacillary load. METHODS: We studied serum
      levels of interferon gamma and interleukin 6 in 100 patients of untreated
      leprosy, compared them with 30 age and sex matched normal healthy controls and co
      related them with different parts of the spectrum and reactional episodes. The
      purpose of this study was to delineate the role of cytokines and their clinical
      implications in the leprosy spectrum and during reactional episodes. RESULTS: We
      observed that mean cytokine levels were significantly higher in the patient group
      as compared to the controls. In the non reactional patient group, pure neuritic
      leprosy patients showed highest levels of INFgamma which were directly
      proportional to the extent of nerve involvement. Lepromatous leprosy patients had
      the highest levels of IL6. Bacteriological index demonstrated a negative and
      positive corelation with INFgamma and IL 6 levels respectively. Type I and Type
      II reactional patients had higher levels of INFgamma and IL 6 respectively as
      compared to nonreactional patients. CONCLUSIONS: Our results suggest that pure
      neuritic leprosy and borderline tuberculoid patients in type I reaction are at
      greatest risk for nerve and tissue damage. Thus cytokines have the potential to
      play a significant role in classification, prognosis and treatment of leprosy.

PMID- 18035774
TI  - Screening for mental disorders in leprosy patients: comparing the internal
      consistency and screening properties of HADS and GHQ-12.
AB  - OBJECTIVE: The aim of the study was to investigate the internal consistency and
      screening properties of the General Health Questionnaire-12 (GHQ-12) and the
      Hospital Anxiety and Depression Scale (HADS) in Turkish patients with leprosy.
      METHODS: The two screening instruments and a fully structured diagnostic
      interview (CIDI) were administered to 65 people drawn from all leprosy inpatient
      units in Turkey between March and June of 2001. The scales were evaluated using
      Cronbach's alpha and Receiver Operating Characteristics (ROC) analyses. For each
      scale, criterion validity was assessed for any psychiatric disorder, depressive
      disorder and anxiety disorder. RESULTS: The Cronbach alpha coefficients for the
      GHQ-12 and HADS were 0.84 and 0.81 respectively. For detecting any psychiatric
      disorder, the optimal cut-off for the GHQ-12 was 4/5 (sensitivity 0.82,
      specificity 0.62). The optimal cut-off for the HADS total score was 12/13
      (sensitivity 0.80, specificity 0.77). CONCLUSION: The results indicate that the
      General Health Questionnaire-12 and Hospital Anxiety and Depression Scale have
      satisfactory internal consistency, and performed well to a similar extent for
      detecting psychiatric disorders in leprosy patients.

PMID- 18035775
TI  - Serum beta-glucuronidase levels in children with leprosy.
AB  - A study was undertaken to find out the usefulness of determining the circulating
      levels of beta-glucuronidase, a lysosomal enzyme in leprosy affected children of
      less than 15 years of age. The serum enzyme levels were significantly higher in
      BB/BL patients compared to healthy control children as well as children with skin
      diseases other than leprosy. Treatment with Multidrug regimen advocated by WHO
      for multi/paucibacillary leprosy resulted in a significant fall in the serum
      enzyme levels in BB and BL cases. The findings suggest that serum beta
      glucuronidase may be a useful parameter for the activity and extent of
      pathogenesis in leprosy.

PMID- 18035776
TI  - Diffuse leprosy of Lucio and Latapi: a histologic study.
AB  - BACKGROUND AND PURPOSE: Ladislao de la Pascua described the spotted or lazarine
      leprosy for first time in 1844. Later on, Lucio and Alvarado studied and
      published it with the same names in 1852. Latapi re-discovered it in 1938 and
      reported it as 'Spotted' leprosy of Lucio in 1948. Frenken named it diffuse
      leprosy of Lucio and Latapi in 1963. Latapi and Chevez-Zamora explained that the
      fundamental condition of this variety of leprosy was a diffuse generalised
      cutaneous infiltration, naming it pure and primitive diffuse lepromatosis, upon
      which necrotising lesions develop, calling these lesions Fenomeno de Lucio or
      erythema necrotisans. A great number of histopathological reports have addressed
      the study of Lucio's phenomenon, and few about the histologic changes that take
      place in the course of diffuse lepromatous leprosy. The purpose of this work is
      to report the histologic findings observed in the study of 170 cutaneous biopsies
      of diffuse leprosy of Lucio and Latapi and 30 of Lucio's phenomenon. METHODS:
      This is a retrospective study, which included the examination of 200 biopsy skin
      specimens from 199 patients with diffuse leprosy at different course of the
      disease. These cases were diagnosed in Mexico from 1970 to 2004. RESULTS: The
      histologic examination revealed a vascular pattern affecting all cutaneous
      vessels, characterised by five outstanding features: a) colonisation of
      endothelial cells by acid-fast bacilli, b) endothelial proliferation and marked
      thickening of vessel walls to the point of obliteration, c) angiogenesis, d)
      vascular ectasia, and e) thrombosis. Necrotising lesions seen in diffuse
      lepromatous leprosy displayed two histopathological patterns: one of them, non
      inflammatory occlusive vasculopathy and, the other one, occlusive vasculopathy,
      leukocytoclastic vasculitis, large neutrophilic infiltrate and lobular
      panniculitis. The first appeared as a result of the course of the occlusive
      vasculopathy produced by the colonisation of endothelial cells by Mycobacterium
      leprae. The second, as a result of a previous occlusive vasculopathy plus a
      leprosy reaction which is considered here as variant of ENL. CONCLUSIONS:
      Endothelial cell injury appears to be the main event in the pathogenesis of
      diffuse leprosy of Lucio and Latapi. Once M. leprae has entered the endothelial
      cell, the micro-organism damages the blood vessels, leading to the specific
      changes seen in this variety of lepromatous leprosy.

PMID- 18035777
TI  - The use of Geographical Information System (GIS) to improve active leprosy case
      finding campaigns in the municipality of Mossoro, Rio Grande do Norte State,
      Brazil.
AB  - There is a high incidence of leprosy in the municipality of Mossor6, Rio Grande
      do Norte state, where the detection coefficient has risen from 2.78/10,000
      population in 1998 to 5.14 in 2004. While cases have been registered throughout
      the urban area, the disease is concentrated in select neighbourhoods. This study
      was undertaken using Geographical Information System (GIS) with the objective of
      defining low-cost, effective strategies to control leprosy. The land registry map
      of the city, Ikonos satellite images and the SINAN (National Morbidity
      Notification Information System) database were used as the cartographical basis
      for the study. The sample for the leprosy mapping was drawn from the 358 new
      cases of the disease diagnosed in the municipality between 1998 and 2002. The
      houses of 281 patients were located (78.5% of the total) and their addresses geo
      referenced using a GPS handheld device. Subsequently, geographical analysis was
      carried out using ArcView 9.0 software showing predominant concentration of cases
      in the neighbourhoods of Barrocas, Santo Antonio, Bom Jardim and Paredoes. This
      mapping served as the basis for four active case finding campaigns conducted in
      the most highly concentrated areas between March and September of 2005. Campaigns
      guided by spatial analysis led to the diagnosis of 104 new cases of the disease
      (50% of the total number of new cases detected in the municipality in 2005). The
      use of GIS in leprosy diagnosis has shown to be extremely effective, providing a
      clear visual understanding of the distribution of the disease in the
      municipality, which results in targeted interventions and important cost
      reductions in leprosy control activities.

PMID- 18035778
TI  - Monitoring impairment in leprosy: choosing the appropriate tool.
AB  - OBJECTIVE: To assess to what extent the Maximum WHO Impairment Grade, the EHF
      Score and Impairment Summary Form (ISF) reflect changes in impairment, both in
      number(s) and severity. DESIGN: The impairment data at registration and at
      release from treatment of 444 persons affected by leprosy registered for MDT from
      1994-2003 in Federal Capital Territory, Nigeria were analysed using three
      monitoring tools. RESULTS: Of the 444 patients, 92 people had a change (10
      deteriorated, 70 improved while 12 had improvement in some parts of their body
      and deterioration in other parts) in their impairment between Registration and
      Release from Treatment. Of the 10 people whose impairment status deteriorated,
      the WHO Grade missed 7 and the EHF score missed 4. The ISF missed none. Of the 70
      whose impairment status improved, the WHO grade missed 27; the EHF score missed
      20 and the ISF missed 9. The WHO Grade had a sensitivity of 50%, the EHF Score
      61% and the ISF 90%. Negative predictive values were 88%, 91% and 98%
      respectively. CONCLUSIONS: The Maximum WHO Impairment Grade use should be limited
      to an indicator of late case detection. The EHF score is better used at programme
      level than individual patient level. The ISF is a sensitive tool for monitoring
      impairments at patient level to aid clinical decision making.

PMID- 18035779
TI  - Current situation of leprosy colonies/leprosaria and their future in P.R. China.
AB  - OBJECTIVE: To identify the current situation of leprosy colonies/leprosaria and
      make some recommendations for improving the quality of life of people affected by
      leprosy in China. METHODS: A national survey using designed forms was carried out
      in 2004. The forms were filled in by local heads responsible for the management
      of leprosy colonies/leprosaria and sent to Provincial and National Centres for
      analysis. RESULTS: China had 605 leprosy colonies/leprosaria with 555 active
      leprosy patients (on treatment) and 18,175 ex-patients (people affected by
      leprosy) living in them at the end of 2004. Among 18,730 patients and people
      affected by leprosy, 13,430 (71.7%) had grade 2 disabilities. Among those with
      visible disability, 6392 (47.6%) lost the ability to take care of themselves due
      to serious deformity. Because of a decrease in health workers working at leprosy
      colonies and a shortage of medical materials, the health care quality of these
      people was neglected. Most colonies/leprosaria were located at remote and
      isolateS places with difficult transportation, and most buildings/houses were in
      danger of collapse because the colonies/leprosaria were built in the 1950's.
      Those affected by leprosy were in great need of help. CONCLUSION: The authors
      recommend that small, remote and isolated leprosy colonies should be closed. New
      leprosaria at District, Provincial or National levels should be established or
      some old leprosaria with good transportation should be reconstructed to house
      those affected by leprosy from closed leprosy colonies/leprosaria. The newly
      established or reconstructed leprosaria could act as centres for reference,
      training, rehabilitation and research on leprosy.

PMID- 18035780
TI  - Azathioprine in controlling type 2 reactions in leprosy: a case report.

PMID- 18035781
TI  - Dermatologists and leprosy in India.

PMID- 18035782
TI  - Informal consultation on rifampicin resistance in leprosy.

PMID- 18035783
TI  - National Workshop on "Is integration a leap forward?--Implications of integration
      on quality care in leprosy", Mumbai.

PMID- 18035784
TI  - ["I am counting on the creativity and spirit of initiative in nurses!" Interview
      by Yasmina Ouharzoune, Regine Clement and Sylvie Warnet].

PMID- 18035786
TI  - [The roots of nursing care].

PMID- 18035787
TI  - [Towards recognition of the profession].

PMID- 18035788
TI  - [Nurse and journalist at the same time. Interview by Sylvie Warnet].

PMID- 18035789
TI  - [Nursing identity and professionalization].

PMID- 18035790
TI  - [Rites of passage].

PMID- 18035791
TI  - ["It is time for the profession to collectively mobilize itself". Interview by
      Sylvie Warnet].

PMID- 18035792
TI  - [Protocol for management of acute pain in the emergency room].

PMID- 18035793
TI  - [Audit on the use of a hydroalcoholic solution].

PMID- 18035794
TI  - [Partial thromboplastin time].

PMID- 18035795
TI  - [Living well with psoriasis].

PMID- 18035796
TI  - A comparative study of patients' preferences and sensory perceptions of three
      forms of inhalers among Thai asthma and COPD patients.
AB  - In 9 study centers, 419 patients with asthma or COPD were randomized to receive
      two forms of salbutamol metered-dose-inhalers (MDIs), i.e. CFC-driven MDI, non
      CFC (HFA) MDI and one salbutamol dry powder inhaler (DPI), in a multi-center,
      comparative, cross-over and randomized study, performed to facilitate the
      formulation of a strategic plan to phase out CFC MDIs. After having received all
      three forms of test products, the patients completed an evaluation questionnaire
      indicating their preferences, likelihood of treatment compliance on each product
      and the easiest one to use. Statistical analysis showed that the CFC MDI was
      significantly less irritating (p < 0.014) but lower in its overall appeal (p <
      0.0001). The "most preferred form to be prescribed" was DPI at 47.5% followed by
      non-CFC at 32.5% and CFC MDI at 20.1%. Concerning the ease of use among the three
      forms of test products, 59.9% of the patients indicated "no difference". Adverse
      events were mild and occurred in only 8.2%. In conclusion, patients' preference
      and sensory perception among the three forms of inhalers were comparable except
      that the CFC MDI was significantly less irritating but lower in its overall
      appeal. DPI was the most preferred and easiest form to use but also the most
      expensive. Taking public health into consideration, a non-CFC MDI with a similar
      market price to the CFC MDI would be the obvious choice in a strategic plan to
      phase out CFC MDIs with the least difficulty to the consumers.

PMID- 18035797
TI  - Prevalence of asthma among preschool children in Edirne, Turkey.
AB  - Allergic diseases generally begin early during childhood, but a late diagnosis is
      common. This study aimed to evaluate the prevalence of asthma and asthma-related
      symptoms among kindergarten children in Edirne, Turkey. 873 subjects based on a
      modified ISAAC questionnaire were included. The prevalence of 'wheezing ever' and
      'wheezing during the previous year' was 23.3% and 8.6%, respectively. Prior
      physician diagnoses existed for 36 of 873 (4.1%) children. The prevalence of
      children undiagnosed with asthma, but reporting asthma-related symptoms was 3.1%,
      51.9% of which had previous beta-agonist prescriptions. However, none of these
      children received inhaled anti-inflammatory medications. In conclusion, it was
      found that a large population of preschool children had undiagnosed respiratory
      symptoms suggestive of asthma. Conducting simple surveys of young children is
      particularly important, as identification of asthma early in the disease course
      will facilitate effective prevention and treatment.

PMID- 18035798
TI  - Is pulmonary arterial pressure affected by allergic rhinitis with nasal
      obstruction?
AB  - Obstructive pathologies of the pulmonary tract may cause various levels of
      hypoxia. To compensate for the hypoxia, pulmonary arterial pressure and pulmonary
      arterial flow may increase. We investigated 35 patients with seasonal allergic
      rhinitis (AR) whether hypoxia caused by AR with a high level of obstruction in
      the airways may lead to an increased pulmonary arterial pressure. An
      echocardiographical evaluation was made following the determination of the
      symptomatic and non-symptomatic symptom scores. We found a positive correlation
      between the symptom scores both in the symptomatic and non-symptomatic periods,
      nasal obstruction scores and the mean pulmonary arterial pressures during these
      periods. Further studies with more cases are needed in order to determine the
      cardiac effects of hypoxia in AR, mainly pulmonary arterial hypertension.

PMID- 18035799
TI  - Prevalence of asthma, rhinitis, and eczema in the university population of
      Phitsanulok, Thailand.
AB  - Allergic diseases have been increasing around the world. Many studies in Thai
      children by ISAAC protocol found an increase in the prevalences of asthma,
      allergic rhinitis and eczema. Nevertheless very few studies in Thai adults have
      been done. The objective of this study was to evaluate the prevalence of asthma,
      allergic rhinitis and eczema among Naresuan University students. Two thousand six
      hundred and ninety-three students (835 males and 1,858 females) completed ISAAC
      standardized written and video questionnaires. The age range was 17-53 years
      (mean 20.0 +/- 3.2 years) of which 97.2% were less than 30 years old. The
      prevalences of allergic rhinitis within the past 12 months and allergic rhinitis
      with concomitant conjunctivitis were 57.4% and 25.6%. The prevalences of wheeze
      within the past 12 months and of diagnosed asthma were 12.1% and 9.8%. The eczema
      prevalence within the past 12 months was 15.0%. Subjects with rhinoconjunctivitis
      had significantly more wheeze within the past 12 months and more asthma than
      those without rhinoconjunctivitis (25.8% and 20.1% vs. 7.6% and 6.3%; p < 0.0001,
      p < 0.0001). The prevalences of wheeze within the past 12 months and asthma in
      males (14.1%, 11.9%) were significantly higher than in females (11.2%, 8.9%) (p =
      0.044 and 0.018, respectively). Similar to a recent study in Bangkok University
      students, our results showed an increasing trend in allergic diseases in the
      adult population of Phitsanulok, Northern Thailand, as compared to a study 2
      decades ago.

PMID- 18035800
TI  - Validation of the diagnostic criteria for atopic dermatitis in the adult Thai
      population.
AB  - Atopic dermatitis is a chronic inflammatory skin disorder, for which it is
      difficult to obtain epidemiologic findings. In a previous study, we suggested the
      following diagnostic criteria for atopic dermatitis in the adult Thai population:
      visible flexural dermatitis, a history of flexural dermatitis, a rash of more
      than six months duration and visible dry skin. However these criteria were not
      validated against physicians' diagnoses. In the present study, we validated these
      diagnostic criteria for atopic dermatitis in the Thai population in a clinical
      setting. A case-controlled study was performed on a total of 259 patients; 33
      subjects with active atopic dermatitis, 26 with inactive atopic dermatitis, 100
      controls presenting with an inflammatory skin disorder other than atopic
      dermatitis and 100 controls without any skin disease. Each patient was examined
      according to the above criteria. Sensitivity, specificity, relative value,
      positive predictive value, and negative predictive value were calculated for each
      individual criterion and for composite criteria. Our data confirmed that in order
      to achieve satisfactory sensitivity and specificity for diagnosing atopic
      dermatitis in Thai people older than 13 years, a patient must have a history of
      flexural dermatitis plus two or more of the other mentioned criteria.

PMID- 18035801
TI  - Human metapneumovirus and respiratory syncytial virus detection in young children
      with acute bronchiolitis.
AB  - This study was conducted to detect human metapneumovirus (hMPV) and respiratory
      syncytial virus (RSV) in young children hospitalized with acute bronchiolitis,
      using reverse transcriptase polymerase chain reaction (RT-PCR). Nasopharyngeal
      secretions were collected from 170 children between 1 and 24 months of age
      admitted to two tertiary hospitals in northeastern Thailand, between 2002 and
      2004. Acute bronchiolitis was defined as the first episode of wheezing associated
      with tachypnea, increased respiratory effort and an upper respiratory tract
      infection. Two-thirds (115/170) were positive for viral etiologies: 64.7% RSV
      (110/170) and 3.5% hMPV (6/170). One patient had a dual infection. hMPV was
      detected between August and November, while RSV was prevalent from July through
      March. The clinical manifestations among the 6 hMPV, RSV and non-RSV-infected
      children were similar. RSV was the leading cause of acute bronchiolitis in young
      children and hMPV had a low prevalence in northeastern Thailand.

PMID- 18035802
TI  - Predisposing factors for nevirapine toxicity among AIDS patients with low
      baseline CD4 count.
AB  - The objective of the study was to determine the predisposing factors and
      incidence of toxicity among AIDS patients treated with a nevirapine (NVP)-based
      regimen in clinical practice. A retrospective cohort study of representative
      samples of AIDS patients treated with a NVP-based regimen was performed. A total
      of 206 adult HIV/AIDS cases with median age (IQR) 33 years (range, 29-38 years),
      51% male, treated between January 2004-December 2005, were included. Most (92.2%)
      of the patients were naive to antiretroviral drug. The incidence of NVP toxicity
      was 1.09/100 person-months. The median onset time was 4 weeks post NVP initiation
      (2.57 weeks for skin toxicity and 12.43 weeks for hepatic toxicity). History of
      drug allergy and NVP toxicity were significantly associated (p = 0.006), as were
      sulfamethoxazole allergy and toxicity (p = 0.015). Regarding concomitant
      medication, concurrent anti-tuberculosis drugs significantly increased the risk
      of NVP associated liver toxicity (p = 0.001). Therefore, it is important to
      monitor adverse events from NVP, including liver function tests among HIV/AIDS
      patients with history of drug allergy, especially against sulfamethoxazole, and
      those concurrently treated with antituberculosis drugs.

PMID- 18035803
TI  - Risk factors and bacterial profiles of urinary tract infections in patients with
      systemic lupus erythematosus.
AB  - Bacteremic urinary tract infection (UTI) is known to carry a high mortality rate,
      especially in immunocompromised patients. Patients with systemic lupus
      erythematosus (SLE) have an immunocompromised status, and thus an increased risk
      of infection. To evaluate the risk factors for UTI in SLE patients and to
      identify factors associated with bacteremic UTI, we reviewed SLE patients
      hospitalized for UTI over a 20-year study period. Based on our results we
      conclude that lupus nephritis is a risk factor for UTI in SLE patients. Clinical
      symptoms do not significantly distinguish bacteremic from non-bacteremic UTI in
      hospitalized SLE patients. Although Escherichia coli remain the most common
      bacteria in UTI, Salmonella spp. might need particular attention because of their
      high likelihood for causing bacteremia.

PMID- 18035804
TI  - Hereditary angioedema: a Taiwanese family with a novel gene mutation.
AB  - Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a
      deficiency of C1 esterase inhibitor (C1-INH). Affected individuals have attacks
      of swelling involving almost any part of the body. We studied a family with 15
      living members, including a 16-year-old girl who had 3 attacks of angioedema in 2
      years. Her paternal uncle had died of asphyxiation during an attack 15 years
      previously. We analyzed the blood of each family member for C3, C4, and C1-INH
      levels and sequenced the SERPING1 (formerly C1NH) gene that codes for C1-INH. Six
      individuals had decreased serum levels of C4 and C1-INH, and they were all found
      to have a single nucleotide A deletion at codon 210 of the gene, 1210fsX210, a
      novel mutation that accounts for the HAE in this family.

PMID- 18035805
TI  - The prevalence and persistence of human parvovirus B19 infection in thalassemic
      patients.
AB  - Human parvovirus B19 infection was studied in 60 thalassemic patients in
      Thailand. Seroprevalence, persistence of parvovirus B19 and their genotypes were
      identified in blood samples. Prevalence of anti-parvovirus B19 IgG and DNA found
      in thalassemic patients were 38% and 13%, respectively. Anti-parvovirus B19 IgM
      could be detected in 4% of these positive anti-parvovirus B19 IgG patients. The
      seroprevalence and parvovirus B19 DNA in patients with a history of blood
      transfusion were not significantly higher than those without such a history (44%
      vs. 34% and 20% vs. 9%, respectively). Phylogenetic analysis of NS1 nucleotide
      sequences of three parvovirus B19 samples revealed that they were parvovirus B19
      genotype 1. They showed low genetic diversity from prototype (Au) strain. We
      concluded that acute and chronic persistent parvovirus B19 infection were found
      in the thalassemic Thai patients. Chronic persistence of parvovirus B19 infection
      might play important clinical role in thalassemic patients because of the high
      prevalence of parvovirus B19 DNA. Blood transfusion had no significant influence
      to increase the prevalence of parvovirus B19 infection in thalassemic patients.

PMID- 18035806
TI  - Seroepidemiology and genotypes of hepatitis C virus in Thailand.
AB  - HCV can be classified into 6 major genotypes based on the phylogenetic analysis
      of the genomic sequences. The 3 major genotypes found in Thailand are 3, 1 and 6,
      respectively. In 2004, an epidemiological survey was carried out to evaluate the
      seroprevalence of HCV infections among populations aged 2-60 years in four
      provinces of Thailand, representing the North, Northeast, Center and South of the
      country, respectively. One hundred and twenty five out of 5,825 serum samples
      (2.15%) were positive for anti-HCV by ELISA. Fifty eight out of 100 anti-HCV
      positive samples (58.0%) were positive by RT-PCR of the 5'UTR. The core region of
      45 representative samples was sequenced allowing classification into genotype
      variants 1a (6.7%), 1b (26.7%), 2a (2.2%), 2c (2.2%), 3a (51.1%), 3b (2.2%) and 6
      (8.9%). This information might be crucial for public health surveillance and
      prevention of HCV infection.

PMID- 18035808
TI  - Research, economic development, and the role of the University of Puerto Rico.

PMID- 18035807
TI  - Dynamics of HBV DNA levels, HBV mutations and biochemical parameters during
      antiviral therapy in a patient with HBeAg-negative chronic hepatitis B.
AB  - Chronic hepatitis B virus (HBV) infection leads to long-term sequelae such as
      cirrhosis and hepatocellular carcinoma. Antiviral therapy aims at controlling the
      viral replication and thus, decreasing the likelihood of such complications. In
      this study, we evaluated the dynamics of biochemical and virological parameters
      over 10 years of antiviral therapy in a Thai patient with chronic HBeAg-negative
      HBV infection, who had relapsed after two courses of interferon alfa treatment.
      Lamivudine administration initially led to a significant reduction in alanine
      aminotransferase (ALT) and HBV DNA levels, but a subsequent emergence of YIDD
      mutants caused an ALT flare and a virus breakthrough. A 4-log HBV DNA decrease
      and normalization of the ALT level were achieved within 3 months of adefovir
      monotherapy without any relapse during follow-up exceeding 20 months. Thus,
      careful monitoring during treatment and knowledge of cross-resistance to
      antiviral salvage therapy are crucial for the management of patients with chronic
      hepatitis B.

PMID- 18035809
TI  - Antimicrobial resistance in 11 hospitals in Puerto Rico: results of an
      antimicrobial resistance management (ARM) program.
AB  - PURPOSE: The Antimicrobial Resistance Management Program (ARMP) was established
      in 1997 at the University of Florida as an ongoing project to document trends in
      antimicrobial susceptibility patterns in inpatient/outpatient isolates and track
      resistance that may occur with specific antibiotic use. METHODS: Institutions are
      enrolled at no charge and provide a minimum of 3 years of antibiogram/sensitivity
      report data, which are reviewed to create a customized analysis of antimicrobial
      susceptibility trends benchmarked against national/regional comparators. The
      data, in a HIPAA-compliant non-identifying format, comprise a national aggregate
      database of 28.4 million isolates from 358 institutions. This database was
      interrogated to determine resistance rates for eleven hospitals in Puerto Rico
      from 1998-2003 and, as comparators, those in the database from the State of
      Florida and all U.S. institutions. RESULTS: Between 1996-2003, data on 328,837
      isolates collected from 11 hospitals throughout Puerto Rico, 5,388,897 isolates
      from 46 institutions in Florida, and 24,951,098 isolates from 358 U.S.
      institutions for the following organisms (number of antibiotics tested against)
      were reviewed for susceptibility: coagulase-negative staphylococci
      (14)/Staphylococcus epidermidis (18), Enterococcus faecalis (7), Enterococcus
      faecium (5), Enterococcus species (4), Escherichia coli (24), Klebsiella
      pneumoniae (24), Proteus mirabilis (22), Pseudomonas aeruginosa (14), Serratia
      marcescens (22), Staphylococcus aureus (23), and Streptococcus pneumoniae (9).
      Antimicrobial resistance in Puerto Rico varied organism to organism from that
      observed in Florida and nationally. CONCLUSIONS: This first broad analysis of
      antimicrobial resistance in Puerto Rico provides important baseline data, both
      for sentinel surveillance programs and for determining strategies for
      intervention.

PMID- 18035810
TI  - Knowledge, attitudes and practices in a group of pharmacists in Puerto Rico
      regarding emergency contraception.
AB  - BACKGROUND: The recent FDA approval of non-prescription sales of Plan B, an
      emergency contraceptive method to those 18 years old and over, gives a prominent
      role to pharmacists in providing timely access to emergency contraception (EC).
      While this decision affects Puerto Rico, no studies on non-prescription EC in
      Puerto Rico have been conducted. The purpose of this study is to identify the
      knowledge, attitudes and practices of a group of pharmacists in Puerto Rico
      regarding emergency contraceptive pills. METHODS: A cross-sectional descriptive
      study of a group of pharmacists' knowledge, attitudes, and practices regarding EC
      was conducted among those who attended the annual convention of the College of
      Pharmacists of Puerto Rico on August 24-26, 2006. RESULTS: Slightly more than
      half of pharmacists surveyed (51.4%) supported a law that allows them to dispense
      EC without a prescription. Yet, overall EC knowledge was low given that the
      average number of knowledge questions answered correctly was 1.8 (SD+/-1.36) out
      of 6. Pharmacists who correctly answered knowledge questions about EC, whose
      pharmacy dispensed EC, and who felt comfortable giving information to a client
      about EC were significantly more likely to support the non-prescription EC law.
      CONCLUSION: Knowledge about EC was low among the pharmacists that were surveyed,
      but there was support for a non-prescription EC policy in Puerto Rico. Increased
      education efforts are needed in this important group of allied health
      professionals.

PMID- 18035811
TI  - Impact of calcium intake on body mass index in Venezuelan adolescents.
AB  - The prevalence of overweight and obesity is increasing worldwide, affecting
      approximately 15% of adolescents in Venezuela, 17% in United States, and more
      than 30% in Mexico and Puerto Rico. Recent studies have shown that dietary
      calcium and dairy intake are associated with body fat. These studies show that a
      high calcium intake results in low body mass index (BMI). Therefore, the
      objective of the present study is to relate calcium intake from foods rich in
      calcium-rich foods to body weight and BMI in a random sample of 100 adolescents,
      aged 13-18 years. Anthropometric measurements (weight and height) were obtained
      for each participant, who also completed a food frequency questionnaire (FFQ),
      modified with calcium-rich foods. Dietary calcium consumption was 1076+/-534 mg/d
      among the adolescents, which represented an adequacy of 90%. A negative and
      significant association was found between calcium intake and BMI in the boys aged
      13-15 years (r=-0.39, p<0.05). This population subgroup exhibited the widest
      range of BMI values among all groups evaluated. This correlation was not found
      among the older boys (aged 16-18 years) or girls, in which BMI was in the normal
      range and with relatively high calcium intake. In conclusion, we found that high
      calcium intake in younger boys was related to a lower BMI. A high calcium intake,
      not only helps to maintain a healthy body weight, but also is essential for
      acquiring peak bone mass in this crucial stage of life.

PMID- 18035812
TI  - Gender differences in drug use and sexual risk behaviors among non-injecting
      heroin users in Puerto Rico.
AB  - INTRODUCTION: During the 1990s non-injected heroin use (NIHU) increased notably
      in several countries. However, very few studies have examined the drug-using
      practices and other problem behaviors of NIHUs. In this study, we compared male
      and female NIHUs from Puerto Rico across a number of domains. METHODS:
      Recruitment proceeded through visits to drug-copping areas and the local hangouts
      in their vicinity. Subjects were eligible if they were 18 to 25 years old, had
      never injected any drugs, and had recently used heroin or cocaine. Study
      participants were administered a computer-assisted personal interview. RESULTS:
      Of the 412 NIHUs recruited at the time of this study, 74 (18.0%) were females.
      Female NIHUs were more likely to report sexual assaults and more likely to
      manifest severe symptomatology of post-traumatic stress disorder than male NIHUs
      (35.1% vs. 3.6%, p<.01, and 40.5% vs. 25.7%, p=.01, respectively). Females were
      less likely to report a source of emotional support than males (86.5% vs. 95.3%,
      p<.01). Close to one in four of the females (23.0%) reported a history of
      sexually transmitted infections, compared to three percent of the males (p<.01).
      HIV seroprevalence among females was 4.3% compared to 0.6% among males (p=.01).
      DISCUSSION: Female heroin users seem to present a host of different needs
      compared to male heroin users. Given the scarcity of existing programs for female
      drug users in Puerto Rico, designing supportive systems that effectively address
      the specific needs of drug-using women should become a high-priority public
      health issue.

PMID- 18035813
TI  - Sexuality among 7th, 8th and 9th grade students in the state of Lara, Venezuela.
      The Global School Health Survey, 2003-2004.
AB  - BACKGROUND: Effective sexual health promotion programs need to be based on
      evidence; this study describes a set of sexual behavioral patterns, education and
      other subjects related to sexual life among 71th, 8th and 9th grade students in
      the State of Lara, Venezuela. METHODS: During 2003 to 2004 school period, 2070
      students filled out the Global School Health Survey (GSHS)--a school based cross
      sectional self-administered survey that explores, among other areas, sexual
      behavior. RESULTS: Students who responded that ever had intercourse, males 27%
      and females 3.8%; by grade, males 18.2% (7th) and 37.6 % (9th), and females 1.9%
      (7th) and 6.2% (9th). The group who had intercourse, 54.9% males and 25.3%
      females had it by age 12; 59% males and 78.6% females were sexually active in the
      past 12 months; 59.2% males and 43.2% females used condom in the last
      intercourse; and 48.3% males and 21.5% females has 2 or more sexual partners in
      their life. A disparity is present in school-based information, >63% for AIDS and
      <32% for sexual abuse. CONCLUSIONS: This study shows that a substantial number of
      students had sexual intercourse initiation at early age (<12), history of
      multiple sexual partners and low prevalence of condom use. An unbalanced coverage
      of information on AIDS and sexual abuse is highly prevalent in the school.
      However, the implementation and evaluation of comprehensive programs on healthy
      sexual life must take into account that still a majority of students report
      abstinence from sexual intercourse.

PMID- 18035814
TI  - Attitudes towards homosexual and lesbians among Puerto Rican Public Health
      graduate students.
AB  - The objective of this study is to identify the attitude toward the homosexuals
      and lesbians among graduate students of General Public Health and Health
      Education Program at School of Public Health, Medical Sciences Campus of the
      University of Puerto Rico. A descriptive-92 graduate students of the
      correlational design was used to carry out the study participated in the study
      General Public Health and Health Education programs. The data collection was
      collected through a self-administered questionnaire. Descriptive and inferential
      statistics (Chi-square and t-test student) were used to data analysis. The 82.6%
      of the participants had a prejudiced attitude toward the homosexuals and the
      lesbians. The 79.3% presented a low distance level. There is a significant
      association among the social distance, homosexual and lesbian educational
      exposure and the years of studies. To develop appropriate strategies to foment
      the acceptance and eliminate the prejudice toward the homosexuals and lesbians in
      the participants, what will impact in a better way of providing quality health
      services.

PMID- 18035815
TI  - A novel technique leading to complete sensory and motor recovery across a long
      peripheral nerve gap.
AB  - Sensory nerve grafts are the "gold standard" for inducing neurological recovery
      in peripheral nerves with a gap. However, the effectiveness of sensory nerve
      grafts is variable, generally not leading to complete sensory and motor recovery,
      with good recovery limited to gaps shorter than 2 cm, and the extent of recovery
      decreasing with increasing graft length. An alternative technique using a conduit
      filled with pure fibrin to bridge a nerve gap leads to only limited neurological
      recovery. We tested the effectiveness of a novel nerve repair technique in which
      a 5-cm long radial nerve gap was repaired using two sural nerve graft surrounded
      by a collage tube filled with pure fibrin. By 1 1/2 years post surgery, the
      patient recovered complete sensory and motor function. In conclusion, this study
      suggests that the combination of pure fibrin surrounding sural nerve grafts is
      responsible for inducing the extensive neurological recovery induced by either
      pure fibrin or sural grafts alone. This technique is presently being tested in a
      clinical trial.

PMID- 18035816
TI  - A novel mutation in limb girdle muscular dystrophy.
AB  - We describe a patient with limb girdle muscular dystrophy with evidence of a
      D596N novel mutation of the LMNA gene. He presented with a dilated cardiomyopathy
      and heart failure. He successfully underwent a cardiac rehabilitation program
      without cardiovascular complications. Clinicians should suspect a variety of a
      wide array of diseases including laminopathy, dystrophinopathy, sarcoglynopathy
      and LGMD 2I. Further studies should focus on determining the specific mode of
      inheritance and genetic testing should be considered in these patients.

PMID- 18035817
TI  - Mycotic aneurysm: a rare complication of vertebral osteomyelitis.
AB  - We report the case of a 49-year-old man that presented with persistent low back
      pain after being treated for vertebral osteomyelitis. An abdominopelvic CT scan
      with intravenous contrast showed a mycotic aneurysm of the abdominal aorta. The
      patient was taken to the operating room where a bypass reconstruction surgery was
      successfully performed. The history, pathophysiology, most common organisms, risk
      factors, and clinical presentation of mycotic aneurysms are discussed. The
      importance of a high index of suspicion for prompt and proper diagnosis and
      treatment, is emphasized to create awareness about this dreadful complication of
      vertebral osteomyelitis.

PMID- 18035818
TI  - Abnormal Trichuris trichiura eggs detected during an epidemiological survey.
AB  - Abnormal eggs of Trichuris trichiura were found in the stools of one of the
      patients during a study on the prevalence of intestinal parasitoses among an
      institutionalized population. The abnormalities observed included great variation
      in shape, size, and color. Similar atypical whipworm eggs have been reported in
      patients after treatment with mebendazole, thiabendazole, tetracloroethylene, and
      dithiazanine. Apparently some anthelminthics have an effect on the reproductive
      system of female T. trichiura, resulting in production of abnormal eggs, which
      could lead to misdiagnosis of the infection, since they can be mistaken as eggs
      of other parasites or artifacts.

PMID- 18035819
TI  - Influence of microwave irradiation on enzymatic properties: applications in
      enzyme chemistry.
AB  - Although microwave-assisted reactions are widely applied in various domains of
      organic chemistry, their use in the area of enzyme chemistry has been rather
      limited, due to the high temperatures associated with the microwave heating:
      Because current technology, allows a good control of reaction parameters, several
      examples of microwave-assisted enzyme chemistry have been reported, using stable
      and effective biocatalysts (modified enzymes). The purpose of this review is to
      highlight the applications and studies on the influence of microwave irradiation
      on enzymatic properties and their application in enzyme chemistry.

PMID- 18035820
TI  - The role of fluorine in medicinal chemistry.
AB  - The small and highly electronegative fluorine atom can play a remarkable role in
      medicinal chemistry. Selective installation of fluorine into a therapeutic or
      diagnostic small molecule candidate can enhance a number of pharmacokinetic and
      physicochemical properties such as improved metabolic stability and enhanced
      membrane permeation. Increased binding affinity of fluorinated drug candidates to
      target protein has also been documented in a number of cases. A further emerging
      application of the fluorine atom is the use of 18F as a radiolabel tracer atom in
      the exquisitely sensitive technique of Positron Emission Tomography (PET)
      imaging. This short review aims to bring together these various aspects of the
      use of fluorine in medicinal chemistry applications, citing selected examples
      from across a variety of therapeutic and diagnostic settings. The increasingly
      routine incorporation of fluorine atom(s) into drug candidates suggests a bright
      future for fluorine in drug discovery and development. A major challenge moving
      forward will be how and where to install fluorine in a rational sense to best
      optimise molecular properties.

PMID- 18035821
TI  - Synthesis of new 4-(E)-alkenylpyrrolo[1,2-a]quinoxalines as antileishmanial
      agents by Suzuki-Miyaura cross-coupling reactions.
AB  - A series of new 4-(E)-alkenylpyrrolo[1,2-a]quinoxaline derivatives, structural
      analogues of alkaloid chimanine B, was synthesized in good yields using efficient
      palladium(0)-catalyzed Suzuki-Miyaura cross-coupling reactions. These new
      compounds were tested for in vitro antiparasitic activity upon Leishmania
      amazonensis and Leishmania infantum strains. Biological results showed activity
      against the promastigote forms of L. amazonensis and L. infantum with IC50
      ranging from 0.5 to 7 microM. From a Structure-Activity Relationships point of
      view, these pharmacological results mainly enlightened the importance of the 4
      lateral C6, C7 or C8 alpha-unsaturated trans-alkenyl chain of unsubstituted
      pyrrolo[1,2-a]quinoxaline moiety.

PMID- 18035822
TI  - Crystal polymorphism of pharmaceuticals: probing crystal nucleation at the
      molecular level.
AB  - Paracetamol, sulfathiazole and L-glutamic acid are presented as examples of
      pharmaceutical crystal polymorphic systems. The effect of N-acylated
      sulfathiazole derivatives (3-6) on sulfathiazole crystallisation is discussed,
      and possible modes of action presented. Methods for the control of the crystal
      polymorphism of L-glutamic acid which utilise the principles of conformation
      mimicry and co-operative binding are presented. The preparation of a series of
      bis-amides of EDTA derived from sulfathiazole, 5-aminoisophthalic acid and 4
      hydroxyaniline (i.e. compounds 9a-c) is presented, as is data on the effect of
      these compounds on the crystallisation of, respectively, sulfathiazole, L
      glutamic acid and paracetamol.

PMID- 18035823
TI  - Quantitative structure-activity relationships studies of antioxidant
      hexahydropyridoindoles and flavonoid derivatives.
AB  - In order to predict the antioxidant activity of 22 pinoline derivatives (1,2,3,4
      tetrahydro-beta-carbolines), two dimensional quantitative-structure activity
      relationships (2D-QSAR) analysis of 19 hexahydropiridoindoles and 12 flavonoids
      was realized. Five statistically significant models were obtained from randomly
      constituted training sets (21 compounds) and subsquently validated with the
      corresponding test sets (10 compounds). Antioxidant activity (pIC50) was
      correlated with 5 molecular descriptors calculated with the software DRAGON. The
      best predictive model (n = 21, q2 = 0.794, N= 2, r2 = 0.888, s = 0.157) could
      offer structural insights into the features conferring a strong antioxidant
      activity to compounds built from a pinoline scaffold prior to their synthesis.

PMID- 18035824
TI  - Synthesis of new isoxazoles and dihydroisoxazoles and in vitro evaluation of
      their antifungal activity.
AB  - New 2-(2,4-dihalogenophenyl)-1-(1H-imidazol-1-yl)-3-(isoxazol-5-yl)propan-2-ols
      and 2-(2,4-dihalogenophenyl)-1-(1H-imidazol-1-yl)-3-(4,5-dihydroisoxazol-5
      yl)propan-2-ols were synthesized by 1,3-dipolar cycloaddition between
      homopropargylic or homoallylic alcohols and in-situ generated nitrile oxide.
      Their antifungal activity was evaluated against Candida albicans, C. glabrata,
      Aspergillus fumigatus and an azole-resistant petite mutant of C. glabrata.
      Preliminary SAR results are discussed.

PMID- 18035825
TI  - Biocatalytic synthesis of 4-pregnen-20,21-diol-3-one, a selective inhibitor of
      human 5alpha-reductase type II.
AB  - Biocatalysis, the conversion of substrates into valuable products by the use of
      enzymes, has some striking advantages in comparison to standard organic chemistry
      for drug synthesis. By biocatalysis, substrates that contain several identical
      reactive groups at different positions can be converted with high regio
      selectivity and enantio-selectivity. In this study, an E. coli isolate (E132) was
      identified which was able to convert the steroid desoxycorticosterone into the
      product 4-pregnen-20,21-diol-3-one in real terms. The product was purified from
      the cell culture supernatant by HPLC and its structure was demonstrated by mass
      spectrometry and NMR spectroscopy. It was tested on inhibition of human 5alpha
      reductases type I and type II. At a concentration of 10 microM, inhibition was
      49.0% for type I and 81.8% for type II, whereas there was no inhibition of human
      aromatase (CYP19) at 20 microM and human 17alpha-hydroxylase-C17,20-lyase (CYP17)
      at 2.5 microM detectable. The IC50 value of 4-pregnen-20,21-diol-3-one for human
      5alpha-reductase type II was determined to be 1.56 microM.

PMID- 18035826
TI  - Synthesis and evaluation of the antimicrobial activity of novel quinazolinones.
AB  - A simple and efficient microwave-assisted methodology for regioselective
      alkylation of exocyclic nitrogen of cyclic amidines was developed and novel N
      alkylated 3,4-dihydropyrazino [2,1-b] quinazolin-6-ones were prepared. Although
      none of the molecules tested have any specific anti-quorum sensing (-QS)
      activity, our result validates the growth tests devised to control the bias of
      the anti-QS tests. Among the molecules studied, compound 2b exhibits interesting
      activity against the Gram-negative bacteria Escherichia coli and Shigella sonnei.

PMID- 18035827
TI  - Characterisation of recombinant human fatty aldehyde dehydrogenase: implications
      for Sjogren-Larsson syndrome.
AB  - Fatty aldehyde dehydrogenase (FALDH) is an NAD+-dependent oxidoreductase involved
      in the metabolism of fatty alcohols. Enzyme activity has been implicated in the
      pathology of diabetes and cancer. Mutations in the human gene inactivate the
      enzyme and cause accumulation of fatty alcohols in Sjogren-Larsson syndrome, a
      neurological disorder resulting in physical and mental handicaps. Microsomal
      FALDH was expressed in E. coli and purified. Using an in vitro activity assay an
      optimum pH of approximately 9.5 and temperature of approximately 35 degrees C
      were determined. Medium- and long-chain fatty aldehydes were converted to the
      corresponding acids and kinetic parameters determined. The enzyme showed high
      activity with heptanal, tetradecanal, hexadecanal and octadecanal with lower
      activities for the other tested substrates. The enzyme was also able to convert
      some fatty alcohol substrates to their corresponding aldehydes and acids, at 25
      30% the rate of aldehyde oxidation. A structural model of FALDH has been
      constructed, and catalytically important residues have been proposed to be
      involved in alcohol and aldehyde oxidation: Gln-120, Glu-207, Cys-241, Phe-333,
      Tyr-410 and His-411. These results place FALDH in a central role in the fatty
      alcohol/acid interconversion cycle, and provide a direct link between enzyme
      inactivation and disease pathology caused by accumulation of alcohols.

PMID- 18035828
TI  - Synthesis of prodrug-type anti-HIV agents conjugating a REVERSE transcriptase
      inhibitor to a HIV-1 integrase inhibitor by a spontaneously cleavable linker.
AB  - Based on the prodrug concept as well as the combination of two different classes
      of anti-HIV agents, we have designed and synthesized a series of anti-HIV double
      drugs consisting of a nucleoside reverse transcriptase inhibitor (NRTI)
      conjugated with an integrase inhibitor (INI) through a spontaneously cleavable
      linker in an effort to enhance the antiviral activity. These conjugates combined
      in their structure a dideoxy-didehydro-nucleoside (ddN) such as d4T and an INI
      such as alpha, gamma-diketo acid (DKA) analogues of L-708,906 and L-731,988
      linked through an appropriate self-immolative spacer. Among these novel bis
      substrate inhibitors, several conjugates exhibited antiviral activity but this
      effect was accompanied for some of them by an increased cytotoxicity by
      comparison to d4T, DKA or even some precursors. These compounds are nevertheless
      interesting candidates for further investigations.

PMID- 18035829
TI  - Synthesis and anti-HIV evaluation of hybrid-type prodrugs conjugating HIV
      integrase inhibitors with d4t by self-cleavable spacers containing an amino acid
      residue.
AB  - In an attempt to combine the anti-HIV inhibitory capacity of reverse
      transcriptase (RT) inhibitors (NRTIs) and integrase (IN) inhibitors (INIs),
      several heterodimer analogues of the previously reported [d4T]-PABC-[INI] and
      [d4T]-OABC-[INI] prototypes have been prepared. In these novel series, we wished
      to extend our results to conjugates which incorporated an enzymatically labile
      aminoacid unit (L-alanine) connected to d4T through a self-immolative para- or
      ortho-aminobenzyl carbonate (PABC or OABC) spacer. Among the novel heterodimers,
      several derivatives show a potent anti-HIV-1 activity, which proved comparable to
      that of the [L-708,906]-PABC-[d4T] Heterodimer A prototype. However, although the
      compounds proved inhibitory to HIV-1, they were less potent than the parent
      compounds from which they were derived.

PMID- 18035830
TI  - Synthesis of new 4-[2-(alkylamino) ethylthio]pyrrolo[1,2-a]quinoxaline and 5-[2
      (alkylamino) ethylthio]pyrrolo[1,2-a]thieno[3,2-e]pyrazine derivatives, as
      potential bacterial multidrug resistance pump inhibitors.
AB  - The synthesis of new 4-[2-(alkylamino)ethylthio]pyrrolo[1,2-a]quinoxaline
      derivatives la-1 is described in five or six steps starting from various
      substituted nitroanilines 2a-e. The bioisostere 5-[2
      (alkylamino)ethylthio]pyrrolo[1,2- a]thieno[3,2-e]pyrazine 1m was also prepared.
      The new derivatives were evaluated as efflux pump inhibitors (EPIs) in a model
      targeting the NorA system of Staphylococcus aureus. The antibiotic susceptibility
      of two strains overproducing NorA, SA-1199B and SA-1, was determined alone and in
      combination with the neo-synthesised compounds by the agar diffusion method and
      MIC determination, in comparison with reserpine and omeprazole taken as reference
      EPIs. A preliminary structure-activity relationship study firstly allowed to
      clarify the influence of the substituents at positions 7 and/or 8 of the
      pyrrolo[1,2-a]quinoxaline nucleus. Methoxy substituted compounds, 1b and 1g, were
      more potent EPIs than the unsubstituted compounds (1a and 1f), followed by
      chlorinated derivatives (1c-d and 1h). Moreover, the replacement of the N,N
      diethylamino group (compounds 1a-e) by a bioisostere such as pyrrolidine
      (compounds 1f-h) enhanced the EPI activity, in contrast with the replacement by a
      piperidine moiety (compounds 1i-k). Finally, the pyrrolo[1,2-a]thieno[3,2
      e]pyrazine compound 1m exhibited a higher EPI activity than its pyrrolo[1,2
      a]quinoxaline analogue la, opening the way to further pharmacomodulation.

PMID- 18035831
TI  - Synthesis of new bisaryl cyclopentathiophene and thienocyclopentoxazolidine
      derivatives as potential cytotoxic agents.
AB  - The synthesis of new bisaryl thienocyclopentoxazolidine derivatives was achieved
      through a Suzuki cross-coupling procedure with the aim to enhance the previously
      reported cytotoxicity of the series. The biological activity, evaluated in the
      NCI's in vitro human disease-oriented tumor cell line screening panel, was
      however partially conserved by the pharmacomodulations.

PMID- 18035832
TI  - Difluoro analogue of UCS15A triggers activation of exogenously expressed c-Src in
      HCT 116 human colorectal carcinoma cells.
AB  - UCS 15A, an antibiotic produced by Streptomyces sp., has been reported to
      specifically disrupt SH3 domain-mediated interactions in eukaryotic cells.
      Interestingly, in the case of the non-receptor tyrosine kinase Src, UCS15A was
      effective in suppressing the SH3 domain-mediated intermolecular rather than
      intramolecular interactions, and thus prevented Src interactions with certain
      downstream effectors without affecting Src kinase activity. Here the synthesis of
      a novel difluoro analogue of UCS15A is described. The effects of this compound
      (8) on Src activity were tested in HCT 116 colorectal carcinoma cells engineered
      for inducible expression of c-Src. The presence of compound (8) resulted in the
      increased activity of the induced c-Src implicating that (8) acts as a c-Src
      activator in vivo. These observations are supported by computer modelling studies
      which suggest that the aldehyde group of (8) may covalently bind to a lysine
      residue in the SH2-kinase linker region situated in the proximity of the SH3
      domain, which could promote a conformational change resulting in increased Src
      activity.

PMID- 18035833
TI  - Synthesis and PC3 androgen-independent prostate cells antiproliferative effect of
      fagaronine derivatives.
AB  - Fagaronine derivatives syntheses were optimized and their effect on PC3 androgen
      independent prostate cell line was evaluated. An assessment of the lipophilicity
      of the benzo[c]phenanthridine derivatives was achieved at pH 7.4 and et 6.7 by
      determining log D.

PMID- 18035834
TI  - Benzothiepin-derived molecular scaffolds for estrogen receptor modulators:
      synthesis and antagonistic effects in breast cancer cells.
AB  - A series of novel benzothiepin-derived compounds are described as potent
      selective modulators of the human estrogen receptor (SERMs). The objective of the
      study is to evaluate the antiproliferative effects of the compounds on human MCF
      7 breast tumor cells. These heterocyclic compounds contain the traditional
      triarylethylene arrangement exemplified by tamoxifen, conformationally restrained
      through the incorporation of the benzothiepin ring system. The compounds
      demonstrated potency at nanomolar concentrations in antiproliferative assays
      against an MCF-7 human breast cancer cell line with low cytotoxicity. The
      compounds exhibited low nanomolar binding affinity for the estrogen receptor (ER)
      with some specificity for ERbeta, and also demonstrate potent antiestrogenic
      properties in the human uterine Ishikawa cell line. The effect of a number of
      functional group substitutions on the ER binding properties of the benzothiepin
      molecular scaffold is explored through a brief computational structure-activity
      relationship investigation with molecular simulation.

PMID- 18035835
TI  - Synthesis and biological evaluation of 3-(azolylmethyl)-1H-indoles and 3-(alpha
      azolylbenzyl)-1H-indoles as selective aromatase inhibitors.
AB  - This present study identifies a number of azolyl-substituted indoles as potent
      inhibitors of aromatase. In the sub-series of 3-(azolylmethyl)-1H-indoles, four
      imidazole derivatives and their triazole analogues were tested. Imidazole
      derivatives 11 and 14 in which the benzyl moiety was substituted by 2-chloro and
      4-cyano groups, respectively, were the most active, with IC50 values ranging
      between 0.054 and 0.050 microM. In the other sub-series, eight 3-(alpha
      azolylbenzyl)-1H-indoles were prepared and tested. Compound 30, the N-ethyl
      imidazole derivative, proved to be an aromatase inhibitor, showing an IC50 value
      of 0.052 microM. All target compounds were further evaluated against 17alpha
      hydroxylase/C17,20-lyase to determine their selectivity profile.

PMID- 18035836
TI  - Long-tail liability law reform.
AB  - There is a need for the law to evolve so that corporations are obliged to make
      proper provision for liabilities to unascertained future creditors. However,
      implementation of long-tail liabilities is far from straightforward and has many
      repercussions for both corporations and personal injury law. In October 2005 the
      Parliamentary Secretary to the Treasurer requested the Corporations and Markets
      Advisory Committee to consider a "referred proposal" designed to achieve
      comprehensive and principled law reform. Analysis of the referred proposal
      reveals many shortcomings, a number of which have been addressed by the Committee
      in its June 2007 Discussion Paper, Long-Tail Liabilities: The Treatment of
      Unascertained Future Personal Injury Claims. This editorial urges further and
      reflective analysis of the referred proposal and of the Committee's tentative
      suggestions in order to achieve a balance among the entitlements of unascertained
      future creditors, other known creditors, shareholders, corporations' financial
      viability, and the conceptual integrity of corporations law.

PMID- 18035837
TI  - Psychiatric injury law in England and Australia--drawing closer together?
AB  - Major differences developed between English and Australian psychiatric injury law
      from about 1990 onwards, particularly in "secondary victim" cases. The House of
      Lords endorsed the traditional restrictions of aftermath, direct perception and
      sudden shock, whereas the High Court of Australia adopted a more enlightened
      approach which relied chiefly on foreseeability of psychiatric injury. In the
      last five years, there are indications that the gap has narrowed a little. The
      English courts, first in medical negligence cases but then more generally, have
      shown that they are now prepared to interpret the aftermath requirement more
      creatively. In Australia, by contrast, the codification of the law on "mental
      harm" has narrowed the law in certain respects, and there is scope for further
      restriction in the process of statutory interpretation. This analysis assesses
      the significance of these developments and attempts to sum up the present
      position.

PMID- 18035838
TI  - Medico-legal issues and driver licensing.
AB  - Legal liability of doctors as a result of decisions regarding the fitness to
      drive of their patients, and the issue of mandatory reporting have emerged as
      major concerns following several recent cases in Australia. Driver Licensing
      Authorities rely on medical advice from the professions in order to exercise
      their statutory responsibility to ensure the competency and safety of their
      licence holders. The question of whether doctors must disclose medical
      information regarding potentially dangerous drivers is a controversial one as is
      the issue of whether doctors can be held legally responsible for decisions based
      on their advice. This column discusses the current situation in Australia in the
      light of these concerns and the implications for Licensing Authorities if
      information is not readily available to them.

PMID- 18035839
TI  - Re Herrington: aboriginality and the quality of human rights jurisprudence in end
      of-life decisions by the Australian judiciary.
AB  - In Re Herrington [2007] VSC 151 (King's Case) the partner and family of an
      Aboriginal woman (diagnosed as being in a persistent vegetative state after an
      accident) sought an order from the Victorian Supreme Court that the decision of
      her treating doctors to withhold further medical treatment be opposed. The
      resultant judicial decision contains a very brief review of the now considerable
      case law in this area, does not mention the increasingly important role of
      clinical ethics committees in this context, or discuss the relevance of recently
      passed human rights legislation in Victoria. Given the statutory requirement for
      judicial reference to international human rights norms in jurisdictions such as
      Victoria and the Australian Capital Territory, and their increasing importance in
      other developed nations, the authors highlight the need for the Australian
      judiciary to lift the quality of their jurisprudence in relation to end-of-life
      cases.

PMID- 18035840
TI  - Totipotent, pluripotent or unipotent stem cells: a complex regulatory enigma and
      fascinating biology.
AB  - The search for sources of human stem cells has become a controversial topic from
      an ethical point of view primarily as it has required the destruction of human
      embryos. The development of alternative techniques that enable the generation of
      pluripotent stem cells from adult cells has opened new avenues of research but
      the generation of such cells has again been controversial since it requires the
      use of human eggs, using a technique called somatic cell nuclear transfer. Since
      the cells so generated have a very small potential to generate an "embryo" and
      since the production of the cell lines requires destruction of that "embryo", a
      further ethical issue arises. This article discusses these issues and suggests a
      framework that may assist their consideration. Finally, the article reviews some
      recent developments that have the potential to remove the need for the use of
      eggs or embryos in the generation of stem cell lines and highlights the danger of
      developing legislation on only our current knowledge.

PMID- 18035841
TI  - The legal risks of quality assurance in Australian public hospitals.
AB  - Quality assurance techniques aim to measure and uphold the quality of patient
      care. Tools have been developed that investigate bad outcomes, and identify
      system errors that may lead to bad outcomes. Hospital administrators are
      motivated to use these tools, but worry that quality assurance may itself cause
      legal risks to a hospital. For example, if a hospital finds and documents
      substandard care, a patient who has suffered a bad outcome might discover this
      and try to use it in litigation against the hospital. This article examines the
      legal doctrine behind document discovery, freedom of information, legal
      professional privilege, medical professional privilege, qualified privilege and
      defamation, to explore how patients and their relatives may, first, come across
      and obtain quality assurance findings, and second, use them in legal action. With
      this knowledge, public hospital administrators might then be able to engage in
      quality assurance without unduly causing legal risk for their hospital.

PMID- 18035842
TI  - Death investigation, the coroner and therapeutic jurisprudence.
AB  - Death investigation by coroners incorporates elements of the adversarial and the
      inquisitorial. Coroners function differently from most other judicial officers in
      the way in which their staff interact with family members of the deceased and in
      the way in which they increasingly function as public health officials with a
      prophylactic orientation. Coroners, both before and at inquest, have the
      potential to have broad-ranging and constructive impacts but also deleterious and
      counter-therapeutic effects. This article analyses how coronial practice and
      coronial law and procedural reform have the potential to draw upon the principles
      of therapeutic jurisprudence,

PMID- 18035843
TI  - The bioethics and law paradox: an argument to maintain separateness with a hint
      of togetherness.
AB  - This article analyses how bioethics and law interact and work together. The first
      half of the article provides definitions of both ethics and bioethics. The
      article then considers a number of different bioethical standpoints to
      demonstrate the variance of views in relation to bioethics. In addition, the
      first half of the article focuses on the different regulatory possibilities in
      regard to bioethical contexts. This demonstrates that law is of central
      importance to bioethics. This part also shows that even though law and ethics are
      often used simultaneously to achieve bioethical goals, law and ethics cannot be
      used interchangeably. Thus, even though it is somewhat inevitable that law will
      be used in the pursuit of the goals of bioethics, bioethics and bioethical
      principle should not be merely a vehicle for law-makers to utilise. The second
      half of the article focuses on the issues of autonomy and consent to demonstrate
      how law and ethics have developed in one of the foundation areas of bioethics.

PMID- 18035844
TI  - Legal pragmatism and the pre-birth continuum: an absence of unifying principle.
AB  - The common law has historically been clear - the rights of the unborn do not
      exist prior to birth. A child becomes a legal person and able to enforce legal
      rights upon being born alive and having a separate existence from her or his
      mother. This article assesses whether new developments in biomedical technologies
      have left this legal principle inviolate and explores what the state of law is in
      relation to pre-birth. It argues that there is a pre-birth continuum where the
      law punctuates points in a lineal timeline fashion as to when a pre-birth "non
      entity" becomes a legal entity. The article concludes that there is no singular
      rule of law with respect to being or becoming a human but rather a collection of
      discrete and increasingly divergent legal categories. This recognition of a pre
      birth continuum or timeline as to the legal recognition of this "non-entity" has
      significant ramifications for the future development of law and impacts on legal
      thinking about what it means to be human.

PMID- 18035845
TI  - Pandemic and public health controls: toward an equitable compensation system.
AB  - There is increasing global concern about the potential impact of pandemic
      infections, including influenza, SARS and bioterrorist attacks involving
      infectious diseases. Many countries have prepared plans for responding to a major
      pandemic. In Australia, the Federal and State pandemic plans include measures
      such as contact tracing, ensuring availability of antimicrobials, quarantine and
      social distancing. Many of these measures would involve severe restrictions on
      individual citizens and small businesses. Issues of compensation for cooperation
      and compliance with pandemic plans need to be addressed in policy discussion. The
      instrumental benefits of compensation in the event of a pandemic have not been
      sufficiently recognised. Greater attention paid now to mechanisms to compensate
      individual and business costs associated with compliance would increase trust in
      government pandemic plans, encourage compliance and reduce the health and
      economic impact of a pandemic.

PMID- 18035846
TI  - Reducing medical complaints and litigation in Malaysia: turning patients' voices
      into opportunities.
AB  - One of the most important ironies of modern health care is that public
      expectations are rising faster than the ability of health services to meet them.
      Patients nowadays no longer want to be treated as passive recipients of medical
      care but as co-producers or partners able to manage their illnesses. Thus, it is
      not surprising that poor communication and failure to take into account the
      patient's perspective are at the heart of most formal complaints and legal
      actions in Malaysia. The difficulties of existing complaint procedures in
      Malaysia have become manifest over the years and this has been accentuated by
      patients becoming more willing to challenge the decisions of medical
      practitioners and health service management in court. To reduce the number of
      complaints and risks of litigation, a more patient-centred approach should be
      adopted. When patients voice their concern by making a complaint or inquiry, this
      should be seen as a unique source of information for health care services on why
      adverse events occur and how to prevent them. As well as reducing future harm to
      patients, better management of complaints should restore trust and reduce the
      risk of litigation, through open communication and a commitment to learn from the
      problem. The existing procedures for patients to be heard in Malaysia should be
      reviewed and incorporate features such as responsiveness, accessibility,
      impartiality, simplicity, speed and accountability.

PMID- 18035847
TI  - Synthesis of peptide substrates for mammalian thioredoxin reductase.
AB  - Mammalian thioredoxin reductase (TR) catalyzes the reduction of the redox-active
      disulfide bond of thioredoxin (Trx) and is similar in structure and mechanism to
      glutathione reductase except for a C-terminal 16-amino acid extension containing
      a rare vicinal selenylsulfide bond. This vicinal selenylsulfide bond is
      essentially a substrate for the enzyme's N-terminal redox center. Here we report
      the synthesis of peptide substrates for the truncated enzyme missing the C
      terminal redox center. We developed a procedure for the synthesis of peptides
      containing cyclic vicinal disulfide/selenylsulfide bonds as well as their
      corresponding acyclic heterodimers. Vicinal disulfide bonds form eight-membered
      ring structures and are difficult to synthesize owing to their propensity to
      dimerize during oxidation. Our procedure makes use of two key improvements for on
      resin disulfide bond formation presented previously by Galande and coworkers
      (Galande AK, Weissleder R, Tung C-H. An effective method of on-resin disulfide
      bond formation in peptides. J. Comb. Chem. 2005; 7: 174-177). First, the addition
      of an amine base to the deprotection solution allows the complete removal of the
      StBu group, allowing it to be replaced with a 5-Npys group. The second
      enhancement is the direct use of a Cys(Mob) or Sec(Mob) derivative as the
      nucleophilic partner instead of utilizing a naked sulfhydryl or selenol. These
      improvements result in the formation of a vicinal disulfide (or selenylsulfide)
      bond in high purity and yield. A direct comparison with the Galande procedure is
      presented. We also present a novel strategy for the formation of an acyclic,
      interchain selenylsulfide-linked peptide (linking H-PTVTGC-OH and H-UG-OH).
      Cysteine analogs of the cyclic and acyclic peptides were also synthesized. The
      results show that the ring structure contributes a factor of 52 to the rate, but
      the presence of selenium in the peptide is more important to catalysis than the
      presence of the ring.

PMID- 18035848
TI  - Elimination and exchange of trifluoroacetate counter-ion from cationic peptides:
      a critical evaluation of different approaches.
AB  - Most synthesized peptides are nowadays produced using solid-phase procedures. Due
      to cleavage and purification conditions, they are mainly obtained in the presence
      of trifluoroacetic acid (TFA) and, for cationic peptides, as trifluoroacetate (TF
      acetate) salts. However, TF-acetate interferes with physicochemical
      characterizations using infrared spectroscopy and might significantly affect the
      in vivo studies. Thus, TF-acetate exchange by another counter-ion is often
      required. Up to now, the classical procedure has consisted of freeze-drying the
      peptide several times in the presence of an excess of a stronger acid than TFA
      (pKa approximately 0): generally HCl (pKa = - 7). This approach means that
      working at pH < 1 can induce peptide degradation. We therefore tested three
      different approaches to exchange the tightly bound TF-acetate counter-ion from
      the dicationic octapeptide lanreotide: (i) reverse-phase HPLC, (ii) ion-exchange
      resin, and (iii) deprotonation/reprotonation cycle of the amino groups. The first
      two approaches allow the partial to almost complete exchange of the TF-acetate
      counter-ion by another ion from an acid weaker than TFA, such as acetic acid (pKa
      = 4.5), and the third requires a basic solution that permits the complete removal
      of TF-acetate counter-ion. The efficiency of these three procedures was tested
      and compared by using different analytical techniques such as 19F-NMR, 1H-NMR and
      attenuated total reflectance Fourier transformed infrared spectroscopy (ATR FT
      IR). We also show that ATR-IR can be used to monitor the TFA removal. The counter
      ion exchange procedures described in this study are easy to carry out, fast,
      harmless and reproducible. Moreover, two of them offer the very interesting
      possibility of exchanging the initial TF-acetate by any other counter-ion.

PMID- 18035849
TI  - Non-invasive detection of hippocampal sclerosis: correlation between metabolite
      alterations detected by (1)H-MRS and neuropathology.
AB  - We assessed (1)H-MRS as a screening tool for detection of hippocampal sclerosis
      in patients with temporal lobe epilepsy (TLE). (1)H-MRS was carried out in the
      hippocampus of 23 patients with unilateral TLE. Metabolite alterations detected
      by (1)H-MRS correlated with degree of segmental neuronal cell loss and amount of
      astrogliosis. Positive correlation was found between total N-Acetylaspartate
      (tNAA) reduction and neuronal density in hippocampal CA1 (P < 0.001), CA3 (P =
      0.015), and CA4 subfields (P = 0.031) and the dentate gyrus (P = 0.006). Neuronal
      cell loss in CA1 turned out to be the most predictive and only significant
      variable for tNAA reduction (P = 0.027). The association between myo-inositol (m
      Ins) and astroglial glial fibrillary acidic protein (GFAP) expression revealed
      significantly increased m-Ins concentrations associated with diffuse astrogliosis
      (m-Ins = 6.4 +/- 1.1 institutional units) compared with gliosis restricted to
      isolated sectors of the hippocampus (i.e. hilus) (m-Ins = 5.2 +/- 1.2
      institutional units) (P = 0.039). A negative correlation was found between m-Ins
      and neuronal loss in the CA4 subfield of the hippocampus (P = 0.028). Our results
      support (1)H-MRS as a suitable non-invasive method for preoperative
      identification of hippocampal sclerosis in patients with TLE. The extent of tNAA
      reduction correlates with hippocampal neuronal cell density. Furthermore, m-Ins
      is associated with the extent of hippocampal astrogliosis.

PMID- 18035850
TI  - Fluoxetine and norfluoxetine analysis by direct injection of human plasma in a
      column switching liquid chromatographic system.
AB  - A column switching LC method is presented for the analysis of fluoxetine (FLU)
      and norfluoxetine (NFLU) by direct injection of human plasma using a lab-made
      restricted access media (RAM) column. A RAM-BSA-octadecyl silica (C-18) column
      (40 mm x 4.6 mm, 10 microm) is evaluated in both backflush and foreflush elution
      modes and coupled with a C-18 lab-made (50 mm x 4.6 mm, 3 microm) analytical
      column in order to perform online sample preparation. Direct injection of 100
      microL of plasma samples is possible with the developed approach. In addition,
      reduction of sample handling is obtained when compared with traditional liquid
      liquid extraction (LLE) and SPE. The total analysis time is around 20 min. A LOQ
      of 15 ng/mL is achieved in a concentration range of 15-500 ng/mL, allowing the
      therapeutic drug monitoring of clinical samples. The precision values achieved
      are lower than 15% for all the evaluated points with adequate recovery and
      accuracy. Furthermore, no matrix interferences are found in the analysis and the
      proposed method shows to be an adequate alternative for analysis of FLU in
      plasma.

PMID- 18035851
TI  - Determination of pesticides in water samples by solid phase extraction and gas
      chromatography tandem mass spectrometry.
AB  - A multiresidue method for the determination of more than 80 pesticides in water
      has been developed and validated. The proposed method is based on SPE followed by
      GC coupled to MS/MS. Different variables affecting SPE procedure, such as
      cartridges, sample volume and solvents were studied, and mass spectrometric
      conditions were optimised in order to increase selectivity and sensitivity.
      Calibration curves were linear over the range of 0.03-0.5 microg/L. Recoveries
      were in the range of 70-110% and repeatability was below 20% for the lowest
      calibration point. LODs ranged from 0.001 to 0.025 microg/L and LOQs from 0.003
      to 0.076 microg/L. Finally, the method was successfully applied to the analysis
      of water samples from southeast of Spain.

PMID- 18035852
TI  - Sensitive determination of aliphatic amines by high-performance liquid
      chromatography with a new fluorogenic probe 3-(4-fluorinebenzoyl)-2-quinoline
      carboxaldehyde.
AB  - A new fluorogenic reagent 3-(4-fluorinebenzoyl)-2-quinoline carboxaldehyde
      (FBQCA) has been synthesized and used as a derivatizing reagent for the
      determination of aliphatic amines with HPLC. The reagent is nonfluorescent, but
      forms highly fluorescent isoindole upon the reaction with primary amines in
      alkaline medium. Eleven amine derivatives were baseline separated in 8 min using
      a gradient elution on a C(8) column and detected with fluorescence detection at
      lambda(ex)/lambda(em) = 480/546 nm. The detection limits were in the range of 0.5
      2 nM (S/N = 3). The proposed method has been successfully applied to the analysis
      of aliphatic amines in food and environmental samples, including white wine,
      soybean oil, soil, and tap water with satisfactory recoveries in the range of 94
      106%.

PMID- 18035853
TI  - Discrimination and identification of the six aromatic positional isomers of
      trimethoxyamphetamine (TMA) by gas chromatography-mass spectrometry (GC-MS).
AB  - A reliable and accurate GC-MS method was developed that allows both mass
      spectrometric and chromatographic discrimination of the six aromatic positional
      isomers of trimethoxyamphetamine (TMA). Regardless of the trifluoroacetyl (TFA)
      derivatization, chromatographic separation of all the investigated isomers was
      achieved by using DB-5 ms capillary columns (30 m x 0.32 mm i.d.), with run times
      less than 15 min. However, the mass spectra of the nonderivatized TMAs, except
      2,4,6-trimethoxyamphetmine (TMA-6), showed insufficient difference for
      unambiguous discrimination. On the other hand, the mass spectra of the TFA
      derivatives of the six isomers exhibited fragments with significant intensity
      differences, which allowed the unequivocal identification of all the aromatic
      positional isomers investigated in the present study. This GC-MS technique in
      combination with TFA derivatization, therefore, is a powerful method to
      discriminate these isomers, especially useful to distinguish the currently
      controlled 3,4,5-trimethoxyamphetmine (TMA-1) and 2,4,5-trimethoxyamphetmine (TMA
      2) from other uncontrolled TMAs.

PMID- 18035854
TI  - Elucidation of urinary metabolites of fluoxymesterone by liquid chromatography
      tandem mass spectrometry and gas chromatography-mass spectrometry.
AB  - The suitability of liquid chromatography tandem mass spectrometry (LC-MS/MS) and
      gas chromatography mass spectrometry (GC-MS) for the elucidation of
      fluoxymesterone metabolism has been evaluated. Electrospray ionization (ESI) and
      collision induced dissociation (CID) fragmentation in LC-MS/MS and electron
      impact spectra (EI) in GC-MS have been studied for fluoxymesterone and two
      commercially available metabolites. MS(n) experiments and accurate mass
      measurements performed by an ion-trap analyser and a QTOF instrument respectively
      have been used for the elucidation of the fragmentation pathway. The neutral loss
      scan of 20 Da (loss of HF) in LC-MS/MS has been applied for the selective
      detection of fluoxymesterone metabolites. In a positive fluoxymesterone doping
      control sample, 9 different analytes have been detected including the parent
      compound. Seven of these metabolites were also confirmed by GC-MS including 5
      previously unreported metabolites. On the basis of the ionization, the CID
      fragmentation, the accurate mass of the product ions and the EI spectra of these
      analytes, a tentative elucidation as well as a proposal for the metabolic pathway
      of fluoxymesterone has been suggested. The presence of these compounds has also
      been confirmed by the analysis of five other positive fluoxymesterone urine
      samples.

PMID- 18035855
TI  - Liquid microjunction surface sampling probe electrospray mass spectrometry for
      detection of drugs and metabolites in thin tissue sections.
AB  - A self-aspirating, liquid microjunction surface sampling probe/electrospray
      emitter mass spectrometry system was demonstrated for use in the direct analysis
      of spotted and dosed drugs and their metabolites in thin tissue sections. Proof
      of-principle sampling and analysis directly from tissue without the need for
      sample preparation was demonstrated first by raster scanning a region on a
      section of rat liver onto which reserpine was spotted. The mass spectral signal
      from selected reaction monitoring was used to develop a chemical image of the
      spotted drug on the tissue. The probe was also used to selectively spot sample
      areas of sagittal whole-body tissue from a mouse that had been dosed orally (90
      mg/kg) with R,S-sulforaphane 3 h prior to sacrifice. Sulforaphane and its
      glutathione and N-acetyl cysteine conjugates were monitored with selected
      reaction monitoring and detected in the stomach and various other tissues from
      the dosed mouse. No signal for these species was observed in the tissue from a
      control mouse. The same dosed-tissue section was used to illustrate the
      possibility of obtaining a lane scan across the whole-body section. In total,
      these results illustrate the potential for rapid screening of the distribution of
      drugs and metabolites in thin tissue sections with the liquid micro-junction
      surface sampling probe/electrospray mass spectrometry approach. Published in 2007
      by John Wiley & Sons, Ltd.

PMID- 18035856
TI  - Hydration/elimination reactions of trapped protonated fluoroalkyl triazines.

PMID- 18035857
TI  - Distance dependence of long-range electron transfer through helical peptides.
AB  - Helical peptides of 8mer, 16mer, and 24mer carrying a disulfide group at the N
      terminal and a ferrocene moiety at the C-terminal were synthesized, and they were
      self-assembled on gold by a sulfur-gold linkage. Infrared reflection-absorption
      spectroscopy and ellipsometry confirmed that they formed a monolayer with upright
      orientation. Cyclic voltammetry showed that the electron transfer from the
      ferrocene moiety to gold occurred even with the longest 24mer peptide.
      Chronoamperometry and electrochemical impedance spectroscopy were carried out to
      determine the standard electron transfer rate constants. It was found that the
      dependence of the electron-transfer rates on the distance was significantly weak
      with the extension of the chain from 16mer to 24mer (decay constant beta = 0.02
      0.04). This dependence on distance cannot be explained by an electron tunneling
      mechanism even if increased hydrogen-bonding cooperativity or molecular dynamics
      is considered. It is thus concluded that this long-range electron transfer is
      operated by an electron hopping mechanism.

PMID- 18035858
TI  - Controlled patterning of peptide nanotubes and nanospheres using inkjet printing
      technology.
AB  - Peptide nanostructures are expected to serve as a major tool in future
      nanotechnological applications owing to their excellent self-assembly properties,
      biological and chemical flexibility and structural simplicity. Yet one of the
      limiting factors for the integration of peptide assemblies into functional
      electro-organic hybrid devices is the controlled patterning of their assemblies.
      Here we report the use of inkjet technology for the application of peptide
      nanostructures on nonbiological surfaces. The aromatic dipeptides nanotubes
      (ADNT) which readily self-assemble in solution were used as an 'ink' and
      patterned on transparency foil and ITO plastic surfaces using a commercial inkjet
      printer. While inkjet technology was used in the past for the patterning of
      carbon nanotubes, it was not used for the deposition of biomolecular
      nanostructures. Furthermore, during the development of the application we were
      able to produce two types of nanostructures, i.e. nanotubes and nanospheres by
      the self-assembly of the same aromatic dipeptide, tertbutoxycarbonyl-Phe-Phe-OH
      (Boc-Phe-Phe-OH), under different conditions. Both spherical and tubular
      structures could be efficiently patterned on surfaces into predesigned patterns.
      The applications of such technology are discussed.

PMID- 18035859
TI  - Electroconductive and photocurrent generation properties of self-assembled
      monolayers formed by functionalized, conformationally-constrained peptides on
      gold electrodes.
AB  - The electroconductive properties and photocurrent generation capabilities of self
      assembled monolayers formed by conformationally-constrained hexapeptides were
      studied by cyclic voltammetry, chronoamperometry, and photocurrent generation
      experiments. Lipoic acid was covalently linked to the N-terminus of the peptides
      investigated to exploit the high affinity of the disulfide group to the gold
      substrates. Smart functionalization of the peptide scaffold with a redox-active
      (TOAC) or a photosensitizer (Trp) amino acid allowed us to study the efficiency
      of peptide-based self-assembled monolayers to mediate electron transfer and
      photoinduced electron transfer processes on gold substrates. Interdigitated
      microelectrodes have shown higher film stability under photoexcitation, lower
      dark currents, and higher sensitivity with respect to standard gold electrodes.

PMID- 18035860
TI  - Role of Ca2+/calmodulin-dependent protein kinase II in development of vascular
      dysfunction in diabetic rats with hypertension.
AB  - We examined the influence of chronic treatment with KN-93 (an inhibitor of
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), 5 mg/kg given every other
      day for 4 weeks) on mean arterial pressure (MAP), urine protein and vascular
      reactivity in streptozotocin (STZ)-induced diabetes in Wistar Kyoto (WKY) and
      spontaneously hypertensive rats (SHR). Treatment with KN-93 did not cause any
      significant changes in body weight, blood glucose or MAP in any of the groups
      studied. However, diabetes-induced elevations in urine volume and protein were
      significantly attenuated in KN-93-treated animals. KN-93-mediated decrease in
      urine volume and protein was more pronounced in SHR compared to WKY rats. The
      increased vascular responsiveness to endothelin-1 and angiotensin II in isolated
      carotid arteries from STZ-treated WKY (D-WKY) and SHR (D-SHR) was normalized by
      chronic treatment with KN-93. Furthermore, chronic treatment with KN-93
      significantly prevented the development of diabetes-induced endothelial
      dysfunction as impaired endothelium-mediated vascular relaxation to carbachol and
      histamine under diabetic conditions was reversed by parallel treatment with the
      inhibitor. These results suggest that signal transduction involving CaMKII
      contributes to the development of abnormal vascular reactivity and renal
      dysfunction during simultaneous occurrence of hypertension and diabetes. We
      conclude that inhibition of CaMKII-mediated signalling could be an effective way
      to antagonize the elevated activities of injury-promoting factors in diabetic
      patients with hypertension.

PMID- 18035862
TI  - Biotherapeutics in the era of biosimilars: what really matters is patient safety.

PMID- 18035863
TI  - Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years
      after the CPMP guidance.
AB  - December 2007 marks the 10-year anniversary of the first regulatory guidance for
      evaluation of drug-induced QT interval prolongation. A decade on, it seems
      surprising that this document, which was released by the Committee on Proprietary
      Medicinal Products, caused such acrimony in the industry. Sponsors now routinely
      evaluate their new drugs for an effect on cardiac electrophysiology in
      preclinical studies, in addition to obtaining ECGs in all phases of drug
      development and conducting a formal thorough QT study in humans.However,
      concurrently, new concerns have also emerged on broader issues related to the
      cardiovascular safety of drugs because of their potential to shorten the QT
      interval as well as to induce proischaemic, profibrotic or prothrombotic effects.
      Drugs may also have an indirect effect by adversely affecting one or more of the
      cardiovascular risk factors (e.g. through fluid retention or induction of
      dyslipidaemia). In addition to peroxisome proliferator-activated receptor
      agonists and cyclo-oxygenase 2 selective inhibitors, three other drugs,
      darbepoetin alfa, pergolide and tegaserod, provide a more contemporary regulatory
      stance on tolerance of cardiovascular risk of drugs and their benefit-risk
      assessment. This recent, more assertive, risk-averse stance has significant
      implications for future drug development. These include the routine evaluation of
      cardiovascular safety for certain classes of drugs. Drugs that are intended for
      long-term use will almost certainly require long-term clinical evaluation in
      studies that enrol populations that most closely resemble the ultimate target
      population. Novel mechanisms of action and biomarkers by themselves are no
      guarantee of improved safety or benefits. Even some traditional biomarkers have
      come to be viewed with scepticism. Requirements for more extensive and earlier
      postmarketing assessment of clinical benefits and rare, but serious risks
      associated with new medicinal products should create a new standard of evidence
      for industry and regulators and almost certainly result in better assessment of
      benefit/risk, more effective and balanced regulatory actions and better care for
      patients.

PMID- 18035864
TI  - Interventions to reduce dosing errors in children: a systematic review of the
      literature.
AB  - Children are a particularly challenging group of patients when trying to ensure
      the safe use of medicines. The increased need for calculations, dilutions and
      manipulations of paediatric medicines, together with a need to dose on an
      individual patient basis using age, gestational age, weight and surface area,
      means that they are more prone to medication errors at each stage of the
      medicines management process. It is already known that dose calculation errors
      are the most common type of medication error in neonatal and paediatric patients.
      Interventions to reduce the risk of dose calculation errors are therefore
      urgently needed. A systematic literature review was conducted to identify
      published articles reporting interventions; 28 studies were found to be relevant.
      The main interventions found were computerised physician order entry (CPOE) and
      computer-aided prescribing. Most CPOE and computer-aided prescribing studies
      showed some degree of reduction in medication errors, with some claiming no
      errors occurring after implementation of the intervention. However, one study
      showed a significant increase in mortality after the implementation of CPOE.
      Further research is needed to investigate outcomes such as mortality and
      economics. Unit dose dispensing systems and educational/risk management
      programmes were also shown to reduce medication errors in children. Although it
      is suggested that 'smart' intravenous pumps can potentially reduce infusion
      errors in children, there is insufficient information to draw a conclusion
      because of a lack of research. Most interventions identified were US based, and
      since medicine management processes are currently different in different
      countries, there is a need to interpret the information carefully when
      considering implementing interventions elsewhere.

PMID- 18035866
TI  - Detection of spironolactone-associated hyperkalaemia following the Randomized
      Aldactone Evaluation Study (RALES).
AB  - INTRODUCTION: A population-based analysis has suggested that the publication of
      the RALES (Randomized Aldactone Evaluation Study) in late 1999 was associated
      with both the wider use of spironolactone to treat heart failure and a
      corresponding increase in hyperkalaemia-associated morbidity and mortality in
      patients also being treated with ACE inhibitors. OBJECTIVES: To gain further
      insight into the reporting of spironolactone-associated hyperkalaemia in an
      independent dataset by analysing the spontaneous reporting experience in relation
      to the publication of RALES, and to determine whether the implementation of a
      commonly used data mining algorithm (DMA) might have directed the attention of
      safety reviewers to the spironolactone/hyperkalaemia association in advance of
      epidemiological findings. METHODS: We calculated the reporting rate of
      spironolactone-associated hyperkalaemia per 1,000 reports per year from 1970
      through to the end of 2005 by identifying relevant cases in the US FDA Adverse
      Event Reporting System. We did this for reports of spironolactone-associated
      hyperkalaemia (where spironolactone was listed as a suspect drug) and according
      to whether the reports listed an ACE inhibitor as a co-suspect or concomitant
      medication. A further statistical analysis of the overall reporting of
      spironolactone (suspect drug)-associated hyperkalaemia was also performed. We
      also performed 3-dimensional (3-D; drug-drug-event) disproportionality analyses
      using a DMA known as the multi-item gamma-Poisson shrinker, which allows the
      calculation and display of a 3-D disproportionality metric known as the
      'interaction signal score' (INTSS). This metric is a measure of the strength of a
      higher order reporting relationship of a triplet (i.e. drug-drug-event)
      association above and beyond what would be expected from the largest
      disproportionalities associated with the individual 2-way associations. RESULTS:
      Visual inspection of a graph of the reporting frequency of spironolactone
      (suspect drug)-associated hyperkalaemia per 1,000 reports was highly suggestive
      of a change point. The t-test on the arcsine-transformed data showed a
      significant difference in reporting of spironolactone-hyperkalaemia combination
      through 1999 compared with 2000 onwards (p < 0.001). When examining the reporting
      time trends according to the presence or absence of an ACE inhibitor, the change
      point seemed to be mostly attributable to an increase in the number of
      spironolactone (suspect drug)-associated hyperkalaemia reports with ACE
      inhibitors listed as a co-suspect drug. No obvious change points in INTSSs for
      spironolactone-ACE inhibitor-hyperkalaemia reports were observed. DISCUSSION:
      Although we could not pinpoint the relative contribution of many possible
      artifacts in the reporting process, as well as increased drug exposure, increased
      adverse event incidence and/or a change in patient monitoring practices, to our
      findings, we observed a notable change in reporting frequency of spironolactone
      associated hyperkalaemia in temporal proximity to the publication of RALES.
      Evidence of this was provided by a trend analysis depicted in a simple graph that
      was supported by statistical analysis. The observed trend was in large part due
      to increased reporting of spironolactone-associated hyperkalaemia with reported
      co-medication with ACE inhibitors. CONCLUSION: These findings are consistent with
      those originally reported in an epidemiological analysis. In this retrospective
      exercise, a simple graph was more illuminating than more complex data mining
      analyses.

PMID- 18035865
TI  - Bodyweight changes associated with antihyperglycaemic agents in type 2 diabetes
      mellitus.
AB  - The majority of patients with type 2 diabetes mellitus are overweight or obese at
      the time of diagnosis, and obesity is a recognised risk factor for type 2
      diabetes and coronary heart disease (CHD). Conversely, weight loss has been shown
      to improve glycaemic control in patients with type 2 diabetes, as well as to
      lower the risk of CHD. The traditional pharmacotherapies for type 2 diabetes can
      further increase weight and this may undermine the benefits of improved glycaemic
      control. Furthermore, patients' desire to avoid weight gain may jeopardise
      compliance with treatment, thereby limiting treatment success and indirectly
      increasing the risk of long-term complications. This review evaluates the
      influences of established and emerging therapies on bodyweight in type 2
      diabetes. Improvement in glycaemic control with insulin secretagogues has been
      associated with weight gain. On the other hand, biguanides such as metformin have
      been consistently shown to have a beneficial effect on weight; metformin appears
      to modestly reduce weight when used as a monotherapy. alpha-Glucosidase
      inhibitors are considered weight neutral; in fact, the results of some studies
      show that they cause reductions in weight. Thiazolidinediones (TZDs) are
      typically associated with weight gain and increased risk of oedema, while the
      impact of some TZDs, such as pioglitazone, on lipid homeostasis could be
      beneficial. Insulin, the most effective therapy when oral agents are ineffective,
      has always been linked to significant weight gain. Newly developed insulin
      analogues can lower the risk of hypoglycaemia compared with human insulin, but
      most have no advantage in terms of weight gain. The basal analogue insulin
      detemir, however, has been demonstrated to cause weight gain to a lesser extent
      than human insulin. The emerging treatments, such as glucagon-like peptide-1
      agonists and the amylin analogue, pramlintide, seem able to decrease weight in
      patients with type 2 diabetes, whereas dipeptidyl peptidase-4 inhibitors seem to
      be weight neutral. In summary, while reduction of hyperglycaemia remains the
      foremost goal in the treatment of patients with type 2 diabetes, the avoidance of
      weight gain may be a clinically important secondary goal. This is already
      possible with careful selection of available therapies, while several emerging
      therapies promise to further extend the options available.

PMID- 18035867
TI  - Comparative safety of long-acting inhaled bronchodilators: a cohort study using
      the UK THIN primary care database.
AB  - BACKGROUND: Use of a long-acting inhaled bronchodilator, either an
      anticholinergic or a beta-adrenergic receptor agonist (beta-agonist), is
      recommended for maintenance treatment of chronic obstructive pulmonary disease
      (COPD). In COPD, the organ system most frequently requiring medical care, other
      than the respiratory system, is the cardiac system. OBJECTIVES: To compare the
      risk of total mortality and certain respiratory and cardiac adverse events among
      users of the two types of recommended long-acting bronchodilators, we conducted a
      cohort study. Specifically, the study compared the safety of the only approved
      long-acting anticholinergic, tiotropium bromide, with the single-ingredient long
      acting beta-agonists (LABAs) salmeterol or formoterol in a broad population of
      users. METHODS: We used automated general practitioner data from the UK THIN (The
      Health Information Network) database as the data source for this study. We used
      Cox proportional hazards models to compute hazard ratio (HR) estimates and 95% CI
      controlling for propensity scores comprising various baseline demographic
      variables, medical therapies and illnesses. RESULTS: The 1061 tiotropium users
      and 1801 LABA users were similar with regard to risk of total mortality (HR 0.93;
      95% CI 0.59, 1.44) and most cardiac events, including angina (HR 0.77; 95% CI
      0.37, 1.59), atrial fibrillation or flutter (HR 0.60; 95% CI 0.25, 1.42),
      myocardial infarction (HR 1.29; 95% CI 0.45, 3.66) and tachycardia (HR 0.66; 95%
      CI 0.29, 1.51). Though imprecise, there was evidence of a decreased risk of heart
      failure (HR 0.65; 95% CI 0.37, 1.12) in tiotropium users. As regards respiratory
      endpoints, the risk of COPD exacerbation (HR 1.15; 95% CI 0.79, 1.67) and
      pneumonia (HR 1.11; 95% CI 0.38, 3.26) were similar among users of each type of
      drug, although there was a decreased risk of asthma exacerbation (HR 0.41; 95% CI
      0.26, 0.64) in tiotropium users compared with LABA users. CONCLUSIONS: Users of
      tiotropium and single-ingredient LABA had similar risk of total mortality and
      cardiovascular endpoints. The decreased risk of asthma exacerbations with
      tiotropium may be due to residual confounding by indication. Confidence limits
      for most events include reduced risks for tiotropium and also small increases in
      risk. Nevertheless, the point estimates suggest that tiotropium was associated
      with a lower risk of each cardiac event except myocardial infarction. However,
      the small number of cases means that further studies are needed to confirm these
      results.

PMID- 18035868
TI  - Analysis of severe hepatic events associated with nevirapine-containing regimens:
      CD4+ T-cell count and gender in hepatitis C seropositive and seronegative
      patients.
AB  - BACKGROUND: Nevirapine-containing regimens have been associated with a risk of
      significant elevations of liver transaminase levels. Higher risk in
      antiretroviral-naive populations has been related to gender and CD4+ T-cell count
      (women with CD4+ T-cell counts of > or =250/mm(3) or men with CD4+ T-cell counts
      of > or =400/mm(3), i.e. group at risk). However, recent studies do not confirm
      this association in HIV populations comprising patients who are antiretroviral
      experienced. Moreover, the predictive value of gender and CD4+ T-cell count on
      the risk of raised transaminase levels has been poorly investigated in
      populations of patients co-infected with hepatitis C virus (HCV). METHODS:
      Analysis of HIV-positive patients receiving nevirapine-containing regimens for
      the first time was conducted. Grade > or =III hepatotoxicity (i.e. > or =5 x
      upper limit of normal in alanine aminotranferase or aspartate aminotransferase
      levels) was the primary endpoint. Univariate and multivariable Cox proportional
      hazard regression models were separately conducted among HCV-antibody (Ab)
      positive and HCV-Ab-negative patients. RESULTS: Amongst 905 patients, 49% were
      HCV-Ab-positive and 79% were antiretroviral-experienced. Grade > or =III liver
      transaminase elevations developed in 7.1% of patients, accounting for an
      incidence of 2.47 (95% CI 1.97, 3.09) per 100 patient-years of follow-up. HCV-Ab
      reactivity was associated with a 3-fold increase in risk of developing relevant
      liver transaminase elevations (95% CI 1.75, 5.3; p < 0.001), whereas gender and
      CD4+ T-cell count did not impact significantly. When analysis was performed in
      HCV-Ab-negative patients, the outcome was independently correlated with the group
      at risk (hazard ratio [HR] 3.66; 95% CI 1.20, 11.14; p = 0.022). By contrast, in
      HCV-Ab-positive patients, the group at risk was not significantly associated with
      the outcome. CONCLUSIONS: Most of the excess rates of relevant raised
      transaminase levels in patients prescribed nevirapine-containing regimens could
      be attributed to HCV co-infection. Gender and CD4+ T-cell count appeared to have
      a statistically significant impact on the risk of relevant transaminase level
      elevations in HCV-negative, but not in HCV-positive patients, probably due to a
      diluting effect of HCV. Incidence of hepatic events after nevirapine-containing
      regimens did not appear to be a major concern in our cohort of patients who were
      mainly antiretroviral-experienced and negative for HCV-Ab. Preferably, nevirapine
      should be avoided in HCV co-infected patients and in males with CD4+ T-cell
      counts of > or =400/mm(3) or females with CD4+ T-cell counts of > or =250/mm(3).

PMID- 18035871
TI  - Formation of rodlike structures of water between oppositely charged ions in
      decane and polyethylene.
AB  - The Gibbs ensemble Monte Carlo method has been combined with the connectivity
      altering osmotic Gibbs ensemble to study water solubility and clustering in
      decane and polyethylene. We show that the presence of oppositely charged ion
      pairs that have fixed positions in the hydrocarbon matrices leads to an order of
      magnitude increase in the water solubility. This is important to a wide range of
      technical applications, since the uptake of the water leads to an increase in
      volume--or expansion--of the hydrocarbon phase which, in the case of
      polyethylene, may change the polymer properties and lead to water treeing. The
      increase in solubility is largest when the ions are sufficiently close so that
      rod-shaped clusters of water molecules form between the ions.

PMID- 18035869
TI  - Re: Age- and gender-specific incidence of hospitalisation for digoxin
      intoxication.

PMID- 18035872
TI  - On the formulation of the material equilibrium condition for a dissolving solid
      nanoparticle.
AB  - Widely known Gibbs' relationship predicting a difference of chemical potentials
      in a small solid particle and in a surrounding fluid phase at equilibrium is
      shown to refer to a real or imaginary bulk phase inside the particle. A similar
      relationship derived for the real surface monolayer of a nanoparticle exhibits
      the equality of chemical potentials at equilibrium, which allows for experimental
      measurement of the surface chemical potential of a dissolving solid nanoparticle.

PMID- 18035873
TI  - Charge-dependent model for many-body polarization, exchange, and dispersion
      interactions in hybrid quantum mechanical/molecular mechanical calculations.
AB  - This work explores a new charge-dependent energy model consisting of van der
      Waals and polarization interactions between the quantum mechanical (QM) and
      molecular mechanical (MM) regions in a combined QMMM calculation. van der Waals
      interactions are commonly treated using empirical Lennard-Jones potentials, whose
      parameters are often chosen based on the QM atom type (e.g., based on
      hybridization or specific covalent bonding environment). This strategy for
      determination of QMMM nonbonding interactions becomes tedious to parametrize and
      lacks robust transferability. Problems occur in the study of chemical reactions
      where the "atom type" is a complex function of the reaction coordinate. This is
      particularly problematic for reactions, where atoms or localized functional
      groups undergo changes in charge state and hybridization. In the present work we
      propose a new model for nonelectrostatic nonbonded interactions in QMMM
      calculations that overcomes many of these problems. The model is based on a
      scaled overlap model for repulsive exchange and attractive dispersion
      interactions that is a function of atomic charge. The model is chemically
      significant since it properly correlates atomic size, softness, polarizability,
      and dispersion terms with minimal one-body parameters that are functions of the
      atomic charge. Tests of the model are examined for rare-gas interactions with
      neutral and charged atoms in order to demonstrate improved transferability. The
      present work provides a new framework for modeling QMMM interactions with
      improved accuracy and transferability.

PMID- 18035874
TI  - Local hybrid functionals: an assessment for thermochemical kinetics.
AB  - Local hybrid functionals with position-dependent exact-exchange admixture are a
      new class of exchange-correlation functionals in density functional theory that
      promise to advance the available accuracy in many areas of application. Local
      hybrids with different local mixing functions (LMFs) governing the position
      dependence are validated for the heats of formation of the extended G3/99 set,
      and for two sets of barriers of hydrogen-transfer and heavy-atom transfer
      reactions (HTBH38 and NHTBH38 databases). A simple local hybrid Lh-SVWN with only
      Slater and exact exchange plus local correlation and a one-parameter LMF,
      g(r)=b(tau(W)(r)tau(r)), performs best and provides overall mean absolute errors
      for thermochemistry and kinetics that are a significant improvement over standard
      state-of-the-art global hybrid functionals. In particular, this local hybrid
      functional does not suffer from the systematic deterioration that standard
      functionals exhibit for larger molecules. In contrast, local hybrids based on
      generalized gradient approximation exchange tend to give rise to nonintuitive
      LMFs, and no improved functionals have been obtained along this route. The LMF is
      a real-space function and thus can be analyzed in detail. We use, in particular,
      graphical analyses to rationalize the performance of different local hybrids for
      thermochemistry and reaction barriers.

PMID- 18035875
TI  - Spatial updating grand canonical Monte Carlo algorithms for fluid simulation:
      generalization to continuous potentials and parallel implementation.
AB  - Spatial updating grand canonical Monte Carlo algorithms are generalizations of
      random and sequential updating algorithms for lattice systems to continuum fluid
      models. The elementary steps, insertions or removals, are constructed by
      generating points in space either at random (random updating) or in a prescribed
      order (sequential updating). These algorithms have previously been developed only
      for systems of impenetrable spheres for which no particle overlap occurs. In this
      work, spatial updating grand canonical algorithms are generalized to continuous,
      soft-core potentials to account for overlapping configurations. Results on two-
      and three-dimensional Lennard-Jones fluids indicate that spatial updating grand
      canonical algorithms, both random and sequential, converge faster than standard
      grand canonical algorithms. Spatial algorithms based on sequential updating not
      only exhibit the fastest convergence but also are ideal for parallel
      implementation due to the absence of strict detailed balance and the nature of
      the updating that minimizes interprocessor communication. Parallel simulation
      results for three-dimensional Lennard-Jones fluids show a substantial reduction
      of simulation time for systems of moderate and large size. The efficiency
      improvement by parallel processing through domain decomposition is always in
      addition to the efficiency improvement by sequential updating.

PMID- 18035877
TI  - Dissociative recombination of H+(H2O)3 and D+(D2O)3 water cluster ions with
      electrons: cross sections and branching ratios.
AB  - Dissociative recombination (DR) of the water cluster ions H(+)(H(2)O)(3) and
      D(+)(D(2)O)(3) with electrons has been studied at the heavy-ion storage ring
      CRYRING (Manne Siegbahn Laboratory, Stockholm University). For the first time,
      absolute DR cross sections have been measured for H(+)(H(2)O)(3) in the energy
      range of 0.001-0.8 eV, and relative cross sections have been measured for
      D(+)(D(2)O)(3) in the energy range of 0.001-1.0 eV. The DR cross sections for
      H(+)(H(2)O)(3) are larger than previously observed for H(+)(H(2)O)(n) (n=1,2),
      which is in agreement with the previously observed trend indicating that the DR
      rate coefficient increases with size of the water cluster ion. Branching ratios
      have been determined for the dominating product channels. Dissociative
      recombination of H(+)(H(2)O)(3) mainly results in the formation of 3H(2)O+H
      (probability of 0.95+/-0.05) and with a possible minor channel resulting in
      2H(2)O+OH+H(2) (0.05+/-0.05). The dominating channels for DR of D(+)(D(2)O)(3)
      are 3D(2)O+D (0.88+/-0.03) and 2D(2)O+OD+D(2) (0.09+/-0.02). The branching ratios
      are comparable to earlier DR results for H(+)(H(2)O)(2) and D(+)(D(2)O)(2), which
      gave 2X(2)O+X (X=H,D) with a probability of over 0.9.

PMID- 18035878
TI  - Fourier transform microwave spectrum of CO-dimethyl ether.
AB  - Two sets of 32 rotational transitions were observed for the carbon monoxide
      dimethyl ether (CO-DME) complex and two sets of 30 transitions for both (13)CO
      DME and C(18)O-DME, in the frequency region from 3.5 to 25.2 GHz, with J ranging
      from 1<--0 up to 7<--6, by using a Fourier transform microwave spectrometer. The
      splittings between the two sets of the same transition varied from 2 to 15 MHz,
      and the two components were assigned to the two lowest states of the internal
      rotation of CO with respect to DME governed by a twofold potential. A preliminary
      analysis carried out separately for the two sets of the observed transition
      frequencies by using an ordinary asymmetric-rotor Hamiltonian indicated that the
      heavy-atom skeleton of the complex was essentially planar, as evidenced by the
      "pseudoinertial defects," i.e., the inertial defects, which involve the
      contributions of the out-of-plane hydrogens of the two methyl groups, I(cc)-I(aa)
      I(bb) of -5.764(23) and -5.753(16) uA(2) for the symmetric and antisymmetric
      states, respectively. All of the observed transition frequencies were
      subsequently analyzed simultaneously, by using a phenomenological Hamiltonian
      which was described in a previous paper on Ar-DME and Ne-DME [Morita et al., J.
      Chem. Phys. 124, 094301 (2006)]. The rotational constants thus derived were
      analyzed to give the distance between the centers of gravity of the two component
      molecules, DME and CO, to be 3.682 A and the angle between the CO and the a
      inertial axes to be 75.7 degrees ; the C end of the CO being closer to the DME.
      Most a-type transitions were observed as closely spaced triplets, which were
      ascribed to the internal rotation of the two methyl tops of DME. The V(3)
      potential barrier was obtained to be 772(2) cm(-1) from the first-order Coriolis
      coupling term between the internal rotation and overall rotation, which is about
      82% of V(3) for the DME monomer, whereas the second-order contribution of the
      coupling to the B rotational constant led to V(3) of 705(3) cm(-1). By assuming a
      Lennard-Jones-type potential, the dissociation energy was estimated to be
      E(B)=1.6 kJ mol(-1), to be compared with 1.0 and 2.5 kJ mol(-1) for Ne-DME and Ar
      DME, respectively.

PMID- 18035879
TI  - Blueshift and intramolecular tunneling of NH3 umbrella mode in 4He n clusters.
AB  - We present diffusion Monte Carlo calculations of the ground and first excited
      vibrational states of NH(3) (4)He(n) for n< or =40. We use the potential energy
      surface developed by one of us [M. P. Hodges and R. J. Wheatley, J. Chem. Phys.
      114, 8836 (2001)], which includes the umbrella mode coordinate of NH(3). Using
      quantum Monte Carlo calculations of excited states, we show that this potential
      is able to reproduce qualitatively the experimentally observed effects of the
      helium environment, namely, a blueshift of the umbrella mode frequency and a
      reduction of the tunneling splittings in ground and first excited vibrational
      states of the molecule. These basic features are found to result regardless of
      whether dynamical approximations or exact calculations are employed.

PMID- 18035880
TI  - Nonlinear optical response of wave packets on quantized potential energy
      surfaces.
AB  - We calculated the dynamics of nuclear wave packets in coupled electron-vibration
      systems and their nonlinear optical responses. We found that the quantized nature
      of the vibrational modes is observed in pump-probe spectra particularly in weakly
      interacting electron-vibration systems such as cyanine dye molecules. Calculated
      results based on a harmonic potential model and molecular orbital calculations
      are compared with experimental results, and we also found that the material
      parameters regarding the geometrical structure of potential energy surfaces are
      directly determined by accurate measurement of time-resolved spectra.

PMID- 18035881
TI  - The gold-ammonia bonding patterns of neutral and charged complexes Au m 0+/-1
      (NH3)n. I. Bonding and charge alternation.
AB  - The gold-ammonia bonding patterns of the complexes which are formed between the
      ammonia clusters (NH(3))(1< or =n< or =3) and gold clusters of different sizes
      that range from one gold atom to the tri-, tetra-, and 20-nanogold clusters are
      governed by two basic and fundamentally different ingredients: the anchoring Au-N
      bond and the nonconventional N-H...Au hydrogen bond. The latter resembles, by all
      features, a conventional hydrogen bond and is formed between a typical
      conventional proton donor N-H group and the gold cluster that behaves as a
      nonconventional proton acceptor. We provide strong computational evidence that
      the gold-ammonia bonding patterns exhibit distinct characteristics as the Z
      charge state of the gold cluster varies within Z=0,+/-1. The analysis of these
      bonding patterns and their effects on the N-H...N H-bonded ammonia clusters are
      the subject of this paper.

PMID- 18035882
TI  - Non-Born-Oppenheimer molecular dynamics of Na...FH photodissociation.
AB  - The accuracy of non-Born-Oppenheimer (electronically nonadiabatic) semiclassical
      trajectory methods for simulations of "deep quantum" systems is reevaluated in
      light of recent quantum mechanical calculations of the photodissociation of the
      Na...FH van der Waals complex. In contrast to the conclusion arrived at in an
      earlier study, semiclassical trajectory methods are shown to be qualitatively
      accurate for this system, thus further validating their use for systems with
      large electronic energy gaps. Product branching in semiclassical surface hopping
      and decay-of-mixing calculations is affected by a region of coupling where the
      excited state is energetically forbidden. Frustrated hops in this region may be
      attributed to a failure of the treatment of decoherence, and a stochastic model
      for decoherence is introduced into the surface hopping method and is shown to
      improve the agreement with the quantum mechanical results. A modification of the
      decay-of-mixing method resulting in faster decoherence in this region is shown to
      give similarly improved results.

PMID- 18035883
TI  - Ab initio study of KN.
AB  - The potential energy curves for the lowest (3)Sigma(-), (3)Pi, and (5)Sigma(-)
      states of the KN molecule have been calculated by the multireference singles and
      doubles configuration interaction method, including Davidson's corrections for
      quadruple excitations [MRCI(+Q)]. It is shown that the former two are bound,
      while the last one is repulsive. The electronic ground state of KN is predicted
      as (3)Sigma(-) state, although the term energy of the (3)Pi state is very small,
      177.3 cm(-1). The binding energy for the (3)Sigma(-) state is evaluated as 0.838
      eV, the rotational constant B(0) as 0.250 63 cm(-1), and harmonic frequency as
      324.4 cm(-1). The spin-orbit coupling effects between the (3)Sigma(-) and (3)Pi
      states of KN are evaluated and discussed. The same MRCI(+Q) computational
      procedures are applied to the isovalent LiN, KC, KO, and KCl to confirm the
      accuracy of present calculations. Theoretical spectroscopic constants presented
      here will inspire experimental studies of KN.

PMID- 18035884
TI  - The rotational spectrum of CoF in all three spin-orbit components of the X3Phi i
      state.
AB  - The pure rotational spectrum of cobalt monofluoride in its X (3)Phi(i) electronic
      state has been measured in the frequency range of 256-651 GHz using direct
      absorption techniques. CoF was created by reacting cobalt vapor with F(2) in
      helium at low pressure (25-30 mTorr). All three spin components were identified
      in the spectrum of this species, two of which exhibited lambda doubling. Each
      spin component showed hyperfine splittings from both nuclei: an octet pattern
      arising from the (59)Co spin of I=72, which is further split into doublets due to
      the (19)F nucleus (I=12). The data were fitted close to experimental precision
      using an effective Hamiltonian expressed in Hund's case (a) form, and rotational,
      fine structure, hyperfine, and lambda-doubling parameters were determined. There
      is evidence that the rotational levels of the highest spin component (3)Phi(2)
      are perturbed. The r(0) bond length of CoF was estimated from the rotational
      constant to be 1.738 014(1) A. This value is in good agreement with previous
      studies but much more accurate. The matrix elements necessary for the complete
      treatment of Lambda doubling in a Phi state have been derived and are presented
      for the first time.

PMID- 18035885
TI  - Dissociative electron attachment to the hydrogen-bound OH in water dimer through
      the lowest anionic Feshbach resonance.
AB  - The lowest energy Feshbach resonance state of the water dimer anion is
      computationally studied as the hydrogen-bonded OH moiety is stretched from its
      equilibrium position toward the hydrogen bond acceptor. The purpose is to treat a
      simple model system to gain insight into how hydrogen bonding may affect
      dissociative electron attachment to water in condensed phases. In the case of a
      water monomer anion, the analogous potential surface is known to be repulsive,
      leading directly to dissociation of H(-). In contrast, in the dimer anion, a
      barrier is found to dissociation of the hydrogen-bonded OH moiety such that the
      migrating hydrogen can be held near the Franck-Condon region in a quasibound
      vibrational state for a time long compared to the OH vibrational period. This
      behavior is found both for the case of an icelike dimer structure and for a
      substantial majority of liquidlike dimer structures. These findings raise the
      possibility that due to effects of hydrogen bonding, a molecule-centered anionic
      entity that is metastable both to electron detachment and to bond dissociation
      may live long enough to be considered as a species in the radiolysis of condensed
      water phases.

PMID- 18035886
TI  - Confinement effects on the glass transition of hydrogen bonded liquids.
AB  - The glass transition behavior of glycerol and propylene glycol confined in
      nanoporous glass is investigated using differential scanning calorimetry. Both
      silanized and unsilanized porous glasses are used to confine the liquids with
      nominal pore sizes ranging from 2.5 to 7.5 nm, and the glass transition
      temperature (T(g)) and the limiting fictive temperature (T(f )') are measured on
      cooling and heating, respectively. The effect of pore fullness is also examined.
      We find that differences in T(g), DeltaC(p), and the enthalpy overshoot behavior
      observed on heating are significant between partially and completely filled pores
      for the case of the unsilanized controlled pore glasses (CPGs) but that the
      effect of pore fullness is insignificant for the silanized CPGs. In general, the
      behavior in the silanized CPGs is similar to the behavior in the completely
      filled unsilanized pores. For glycerol, this includes a small depression in T(f
      )' on the order of 5 K at 2.5 nm. For propylene glycol, similar behavior is found
      except that an additional glass transition is observed in both silanized and
      unsilanized systems approximately 30 K higher than the bulk and a slightly
      smaller depression on the order of 3 K at 2.5 nm is observed in the completely
      filled unsilanized pores and in partially and completely filled silanized pores.
      The results are compared to those in the literature, and the confinement effects
      are discussed.

PMID- 18035887
TI  - Relaxation time, diffusion, and viscosity analysis of model asphalt systems using
      molecular simulation.
AB  - Molecular dynamics simulation was used to calculate rotational relaxation time,
      diffusion coefficient, and zero-shear viscosity for a pure aromatic compound
      (naphthalene) and for aromatic and aliphatic components in model asphalt systems
      over a temperature range of 298-443 K. The model asphalt systems were chosen
      previously to represent real asphalt. Green-Kubo and Einstein methods were used
      to estimate viscosity at high temperature (443.15 K). Rotational relaxation times
      were calculated by nonlinear regression of orientation correlation functions to a
      modified Kohlrausch-Williams-Watts function. The Vogel-Fulcher-Tammann equation
      was used to analyze the temperature dependences of relaxation time, viscosity,
      and diffusion coefficient. The temperature dependences of viscosity and
      relaxation time were related using the Debye-Stokes-Einstein equation, enabling
      viscosity at low temperatures of two model asphalt systems to be estimated from
      high temperature (443.15 K) viscosity and temperature-dependent relaxation time
      results. Semiquantitative accuracy of such an equivalent temperature dependence
      was found for naphthalene. Diffusion coefficient showed a much smaller
      temperature dependence for all components in the model asphalt systems.
      Dimethylnaphthalene diffused the fastest while asphaltene molecules diffused the
      slowest. Neat naphthalene diffused faster than any component in model asphalts.

PMID- 18035888
TI  - Quadrupolar nuclear magnetic resonance spectroscopy in solids using frequency
      swept echoing pulses.
AB  - The acquisition of ideal powder line shapes remains a recurring challenge in
      solid-state wideline nuclear magnetic resonance (NMR). Certain species,
      particularly quadrupolar spins in sites associated with large electric field
      gradients, are difficult to excite uniformly and with good efficiencies. This
      paper discusses some of the opportunities that arise upon departing from standard
      spin-echo excitation approaches and switching to echo sequences that use low
      power, frequency-swept radio frequency (rf) pulses instead. The reduced powers
      demanded by such swept rf fields allow one to excite spins in different
      crystallites efficiently and with orientation-independent pulse angles, while the
      large bandwidths of interest that are needed by the measurement can be covered,
      thanks to the use of broadband frequency sweeps. The fact that the spins'
      evolution and ensuing dephasing starts at the beginning of such rf manipulation
      calls for the use of spin-echo sequences; a number of alternatives capable of
      providing the desired line shapes both in the frequency and in the time domains
      are introduced and experimentally demonstrated. Sensitivity- and lineshape-wise
      these experiments are competitive vis-a-vis current implementations of wideline
      quadrupolar NMR based on hard rf pulses; additional opportunities that may derive
      from these ideas are also briefly discussed.

PMID- 18035889
TI  - Configuration-selective spectroscopic studies of Er3+ centers in ErSc2N@C80 and
      Er2ScN@C80 fullerenes.
AB  - Low temperature photoluminescence (PL) and photoluminescence excitation (PLE)
      spectroscopy of high purity ErSc(2)N@C(80) and Er(2)ScN@C(80) fullerenes reveal
      at least two metastable configurations of the Er(3+) ion within the cage,
      consistent with previous observations from x-ray diffraction. Using PLE
      measurements at a number of different emission wavelengths we have characterized
      the ground state, (4)I(152), and the first excited state, (4)I(132), of the
      various Er(3+) configurations and their crystal-field splitting. We present
      detailed energy level diagrams for the ground and excited states of the two
      dominant configurations of ErSc(2)N@C(80) and Er(2)ScN@C(80).

PMID- 18035890
TI  - Vibrational relaxation in simulated two-dimensional infrared spectra of two amide
      modes in solution.
AB  - Two-dimensional infrared spectroscopy is capable of following the transfer of
      vibrational energy between modes in real time. We develop a method to include
      vibrational relaxation in simulations of two-dimensional infrared spectra at
      finite temperature. The method takes into account the correlated fluctuations
      that occur in the frequencies of the vibrational states and in the coupling
      between them as a result of interaction with the environment. The fluctuations
      influence the two-dimensional infrared line shape and cause vibrational
      relaxation during the waiting time, which is included using second-order
      perturbation theory. The method is demonstrated by applying it to the amide-I and
      amide-II modes in N-methylacetamide in heavy water. Stochastic information on the
      fluctuations is obtained from a molecular dynamics trajectory, which is converted
      to time dependent frequencies and couplings with a map from a density functional
      calculation. Solvent dynamics with the same frequency as the energy gap between
      the two amide modes lead to efficient relaxation between amide-I and amide-II on
      a 560 fs time scale. We show that the cross peak intensity in the two-dimensional
      infrared spectrum provides a good measure for the vibrational relaxation.

PMID- 18035891
TI  - A site-renormalized molecular fluid theory.
AB  - The orientation-dependent pair distribution function for molecular fluids on site
      site potentials is expanded in a topological analog of the diagrammatically
      proper site-site theory of liquids [D. Chandler et al., Mol. Phys. 46, 1335
      (1982)]. The resulting functions are then used to diagrammatically renormalize
      the molecular fluid theory. A result is that the diagrammatically proper
      interaction site model theory is shown to be a linearized, minimal angular basis
      set approximation to this site-renormalized molecular theory. This framework is
      used to propose a new, exact, and proper closure to the diagrammatically proper
      interaction site model theory. The resulting equation system contains a bridge
      function expansion in the proper site-site theory. In addition, the construction
      of the theory is such that the molecular pair distribution function, in full
      dimensionality, is intrinsic to the theory. Furthermore, the theory is equivalent
      to the molecular Ornstein-Zernike treatment of site-site molecules in the basis
      set expansion of Blum and Torruella [J. Chem. Phys. 56, 303 (1971)]. A
      significant formal result of the theory is the demonstration that certain classes
      of diagrams which would otherwise be considered improper in the interaction site
      model formalism are included in the angular expansion of molecular interactions.
      Numerical results for several apolar homonuclear models and an apolar
      heteronuclear model are shown to quantitatively improve upon those of reference
      interaction site model and our recent proper variant with respect to simulation.
      Significant numerical results are that the various thermodynamic quantities obey
      the exact symmetries and sum rules within numerical error for the different sites
      in the heteronuclear case, even for the low order approximation used in this
      work, and the theory is independent of the so-called auxiliary site problem
      common to previous site-site theories.

PMID- 18035892
TI  - High-temperature phase transitions in CsH2PO4 under ambient and high-pressure
      conditions: a synchrotron x-ray diffraction study.
AB  - To clarify the microscopic origin of the temperature-induced three-order-of
      magnitude jump in the proton conductivity of CsH(2)PO(4) (superprotonic
      behavior), we have investigated its crystal structure modifications within the 25
      300 degrees C temperature range under both ambient- and high-pressure conditions
      using synchrotron x-ray diffraction. Our high-pressure data show no indication of
      the thermal decomposition/polymerization at the crystal surface recently proposed
      as the origin of the enhanced proton conductivity [Phys. Rev. B 69, 054104
      (2004)]. Instead, we found direct evidence that the superprotonic behavior of the
      title material is associated with a polymorphic structural transition to a high
      temperature cubic phase. Our results are in excellent agreement with previous
      high-pressure ac impedance measurements.

PMID- 18035893
TI  - Chiral response of single walled carbon nanotube based sensors to adsorption of
      amino acids: a theoretical model.
AB  - Calculations of the interaction energy and dielectric responses of chiral single
      walled carbon nanotubes to the presence of amino acid enantiomers are carried
      out. A theoretical study is developed to show that the frequency shifts of
      selected nanotubes conveniently tailored to the size of the probed molecules and
      used in a resonator configuration can selectively detect different species of
      amino acids and the left- and right-handed enantiomers of these species. Criteria
      for an optimization of the adsorption energy and frequency response on the size
      and chiral angle of the nanotubes are given. It is found that a very small set of
      carbon tubes obeys these conditions.

PMID- 18035894
TI  - Mechanisms and energetics of hydride dissociation reactions on surfaces of plasma
      deposited silicon thin films.
AB  - We report results from a detailed analysis of the fundamental silicon hydride
      dissociation processes on silicon surfaces and discuss their implications for the
      surface chemical composition of plasma-deposited hydrogenated amorphous silicon
      (a-Si:H) thin films. The analysis is based on a synergistic combination of first
      principles density functional theory (DFT) calculations of hydride dissociation
      on the hydrogen-terminated Si(001)-(2x1) surface and molecular-dynamics (MD)
      simulations of adsorbed SiH(3) radical precursor dissociation on surfaces of MD
      grown a-Si:H films. Our DFT calculations reveal that, in the presence of fivefold
      coordinated surface Si atoms, surface trihydride species dissociate sequentially
      to form surface dihydrides and surface monohydrides via thermally activated
      pathways with reaction barriers of 0.40-0.55 eV. The presence of dangling bonds
      (DBs) results in lowering the activation barrier for hydride dissociation to 0.15
      0.20 eV, but such DB-mediated reactions are infrequent. Our MD simulations on a
      Si:H film growth surfaces indicate that surface hydride dissociation reactions
      are predominantly mediated by fivefold coordinated surface Si atoms, with
      resulting activation barriers of 0.35-0.50 eV. The results are consistent with
      experimental measurements of a-Si:H film surface composition using in situ
      attenuated total reflection Fourier transform infrared spectroscopy, which
      indicate that the a-Si:H surface is predominantly covered with the higher
      hydrides at low temperatures, while the surface monohydride, SiH((s)), becomes
      increasingly more dominant as the temperature is increased.

PMID- 18035895
TI  - Including lateral interactions into microkinetic models of catalytic reactions.
AB  - In many catalytic reactions lateral interactions between adsorbates are believed
      to have a strong influence on the reaction rates. We apply a microkinetic model
      to explore the effect of lateral interactions and how to efficiently take them
      into account in a simple catalytic reaction. Three different approximations are
      investigated: site, mean-field, and quasichemical approximations. The obtained
      results are compared to accurate Monte Carlo numbers. In the end, we apply the
      approximations to a real catalytic reaction, namely, ammonia synthesis.

PMID- 18035896
TI  - Optical properties of pentacene and perfluoropentacene thin films.
AB  - The optical properties of pentacene (PEN) and perfluoropentacene (PFP) thin films
      on various SiO(2) substrates were studied using variable angle spectroscopic
      ellipsometry. Structural characterization was performed using x-ray reflectivity
      and atomic force microscopy. A uniaxial model with the optic axis normal to the
      sample surface was used to analyze the ellipsometry data. A strong optical
      anisotropy was observed, and enabled the direction of the transition dipole of
      the absorption bands to be determined. Furthermore, comparison of the optical
      constants of PEN and PFP thin films with the absorption spectra of the monomers
      in solution shows significant changes due to the crystalline environment.
      Relative to the monomer spectrum, the highest occupied molecular orbital to
      lowest unoccupied molecular orbital transition observed in PEN (PFP) thin film is
      reduced by 210 meV (280 meV). A second absorption band in the PFP thin film shows
      a slight blueshift (40 meV) compared to the spectrum of the monomer with its
      transition dipole perpendicular to that of the first absorption band.

PMID- 18035897
TI  - Collective vibrations in cluster models for semiconductor surfaces: vibrational
      spectra of acetylenyl and methylacetylenyl functionalized Si(111).
AB  - The geometries and harmonic vibrational frequencies of the acetylenyl and
      methylacetylenyl functionalized Si(111) surfaces are investigated using quantum
      chemical calculations. The vibrational spectra are computed using a previously
      introduced method whereby the collective vibrational modes that correspond to the
      vibrations of the infinite periodic system are derived from modest sized cluster
      models. Our predictions should be useful for the interpretation of the
      experimental spectra when they become available. The symmetry elements of the
      methylacetylenyl Si(111) surface that are derived from the space group of the
      optimized structure and a vibrational mode resulting from photon-adsorbate
      coupling are explored.

PMID- 18035898
TI  - Computational modeling of nanorod growth.
AB  - In this computational study, we used molecular dynamics and the embedded atom
      method to successfully reproduce the growth of gold nanorod morphologies from
      starting spherical seeds in the presence of model surfactants. The surfactant
      model was developed through extensive systematic attempts aimed at inducing
      nonisotropic nanoparticle growth in strictly isotropic computational growth
      environments. The aim of this study was to identify key properties of the
      surfactants which were most important for the successful anisotropic growth of
      nanorods. The observed surface and collective dynamics of surfactants shed light
      on the likely growth phenomena of real nanoprods. These phenomena include the
      initial thermodynamically driven selective adsorption, segregation, and
      orientation of the surfactant groups on specific crystallographic surfaces of
      spherical nanoparticle seeds and the kinetic elongation of unstable surfaces due
      to growth inhibiting surfactants on those surfaces. Interestingly, the model not
      only reproduced the growth of nearly all known nanorod morphologies when starting
      from an initial fcc or fivefold seed but also reproduced the experimentally
      observed failure of nanorod growth when starting from spherical nanoparticles
      such as the I(h) morphology or morphologies containing a single twinning plane.
      Nanorod morphologies observed in this work included fivefold nanorods, fcc
      crystalline nanorods in the [100] direction and [112] directions and the more
      exotic "dumbell-like" nanorods. Non-nanorod morphologies observed included the
      I(h) and the nanoprism morphology. Some of the key properties of the most
      successful surfactants seemed to be suggestive of the important but little
      understood role played by silver ions in the growth process of real nanorods.

PMID- 18035899
TI  - Infrared spectroscopy of physisorbed and chemisorbed N2 in the Pt(111)(3x3)N2
      structure.
AB  - Using infrared spectroscopy and low electron energy diffraction, we have
      investigated the adsorption of N(2), at 30 K, on the Pt(111) and the
      Pt(111)(1x1)H surfaces. At monolayer coverage, N(2) orders in commensurate (3x3)
      structures on both surfaces, and we propose that the unit cells contain four
      molecules in each case. The infrared spectra reveal that N(2) exclusively
      physisorbs on the Pt(111)(1x1)H surface, while both physisorbed and chemisorbed
      N(2) is detected on the Pt(111) surface. Physisorbed N(2) is the majority species
      in the latter case, and the two adsorption states show an almost identical uptake
      behavior, which indicates that they are intrinsic constituents of the growing
      (3x3) N(2) islands. An analysis of the infrared absorbance data, based on a
      simple scaling concept suggested by density functional theory calculations,
      supports a model in which the (3x3) unit cell contains one chemisorbed molecule
      in end-on atop configuration and three physisorbed molecules. We note that a
      classic "pinwheel" structure on a hexagonal lattice, with the end-on chemisorbed
      N(2) molecules acting as "pins," is compatible with this composition.

PMID- 18035900
TI  - Electrical transport properties of semiconducting lithium molybdate glass
      nanocomposites.
AB  - We have reported the formation of lithium molybdate glass nanocomposites embedded
      with lithium molybdate nanophases from the x-ray diffraction and transmission
      electron microscopic studies. We have investigated the dc electrical conductivity
      in a wide temperature range for these glass nanocomposites, which exhibit
      semiconducting behavior. We have analyzed the dc electrical data in the light of
      polaronic conduction models of Mott and Schnakenberg. We have also studied ac
      electrical conductivity of these glass nanocomposites in wide temperature and
      frequency ranges. The experimental ac results have been analyzed with reference
      to various theoretical models based on quantum-mechanical tunneling and hopping
      over the barrier. We have observed that the temperature dependence of the dc
      conductivity is consistent with the polaronic hopping models, while the
      temperature and frequency dependence of the ac conductivity is consistent with
      the polaronic tunneling models.

PMID- 18035901
TI  - An efficient nonequilibrium Green's function formalism combined with density
      functional theory approach for calculating electron transport properties of
      molecular devices with quasi-one-dimensional electrodes.
AB  - An efficient self-consistent approach combining the nonequilibrium Green's
      function formalism with density functional theory is developed to calculate
      electron transport properties of molecular devices with quasi-one-dimensional
      (1D) electrodes. Two problems associated with the low dimensionality of the 1D
      electrodes, i.e., the nonequilibrium state and the uncertain boundary conditions
      for the electrostatic potential, are circumvented by introducing the
      reflectionless boundary conditions at the electrode-contact interfaces and the
      zero electric field boundary conditions at the electrode-molecule interfaces.
      Three prototypical systems, respectively, an ideal ballistic conductor, a high
      resistance tunnel junction, and a molecular device, are investigated to
      illustrate the accuracy and efficiency of our approach.

PMID- 18035902
TI  - Photoinduced bimolecular electron transfer kinetics in small unilamellar
      vesicles.
AB  - Photoinduced electron transfer (ET) from N,N-dimethylaniline to some coumarin
      derivatives has been studied in small unilamellar vesicles (SUVs) of the
      phospholipid, DL-alpha-dimyristoyl-phosphatidylcholine, using steady-state and
      time-resolved fluorescence quenching, both below and above the phase transition
      temperature of the vesicles. The primary interest was to examine whether Marcus
      inversion [H. Sumi and R. A. Marcus, J. Chem. Phys. 84, 4894 (1986)] could be
      observed for the present ET systems in these organized assemblies. The influence
      of the topology of SUVs on the photophysical properties of the reactants and
      consequently on their ET kinetics has also been investigated. Absorption and
      fluorescence spectral data of the coumarins in SUVs and the variation of their
      fluorescence decays with temperature indicate that the dyes are localized in the
      bilayer of the SUVs. Time-resolved area normalized emission spectra analysis,
      however, reveals that the dyes are distributed in two different microenvironments
      in the SUVs, which we attribute to the two leaflets of the bilayer, one toward
      bulk water and the other toward the inner water pool. The microenvironments in
      the two leaflets are, however, not indicated to be that significantly different.
      Time-resolved anisotropy decays were biexponential for all the dyes in SUVs, and
      this has been interpreted in terms of the compound motion model according to
      which the dye molecules can experience a fast wobbling-in-cone type of motion as
      well as a slow overall rotating motion of the cone containing the molecule. The
      expected bimolecular diffusion-controlled rates in SUVs, as estimated by
      comparing the microviscosities in SUVs (determined from rotational correlation
      times) and that in acetonitrile solution, are much slower than the observed
      fluorescence quenching rates, suggesting that reactant diffusion (translational)
      does not play any role in the quenching kinetics in the present systems.
      Accordingly, clear inversions are observed in the correlation of the fluorescence
      quenching rate constants k(q) with the free energy change, DeltaG(0) of the
      reactions. However, the coumarin dyes, C152 and C481 (cf. Scheme 1), show
      unusually high k(q) values and high activation barriers, which is not expected
      from Marcus ET theory. This unusual behavior is explained on the basis of
      participation of the twisted intramolecular charge transfer states of these two
      dyes in the ET kinetics.

PMID- 18035903
TI  - Quantization of the dipole moment and of the end charges in push-pull polymers.
AB  - A theorem for end-charge quantization in quasi-one-dimensional stereoregular
      chains is formulated and proved. It is a direct analog of the well-known theorem
      for surface charges in physics. The theorem states the following: (1) Regardless
      of the end groups, in stereoregular oligomers with a centrosymmetric bulk, the
      end charges can only be a multiple of 12 and the longitudinal dipole moment per
      monomer p can only be a multiple of 12 times the unit length a in the limit of
      long chains. (2) In oligomers with a noncentrosymmetric bulk, the end charges can
      assume any value set by the nature of the bulk. Nonetheless, by modifying the end
      groups, one can only change the end charge by an integer and the dipole moment p
      by an integer multiple of the unit length a. (3) When the entire bulk part of the
      system is modified, the end charges may change in an arbitrary way; however, if
      upon such a modification the system remains centrosymmetric, the end charges can
      only change by multiples of 12 as a direct consequence of (1). The above
      statements imply that-in all cases-the end charges are uniquely determined,
      modulo an integer, by a property of the bulk alone. The theorem's origin is a
      robust topological phenomenon related to the Berry phase. The effects of the
      quantization are first demonstrated in toy LiF chains and then in a series of
      trans-polyacetylene oligomers with neutral and charge-transfer end groups.

PMID- 18035904
TI  - Structure, dynamics, and phase transitions of tethered membranes: a Monte Carlo
      simulation study.
AB  - A coarse-grained model of a self-avoiding tethered membrane with hexagonal
      coordination, embedded in three-dimensional space, is studied by means of
      extensive Monte Carlo computer simulations. The simulations are performed at
      various temperatures for membranes with linear size 5< or =L< or =50. We find
      that the membrane undergoes several folding transitions from a high-temperature
      flat phase to multiple-folded structure as the temperature is steadily decreased.
      Using a suitable order parameter and finite size scaling analysis, these phase
      transitions are shown to be of first order. The equilibrium shape of the
      membranes is analyzed by calculating the eigenvalues lambda(max) (2)> or
      =lambda(med) (2)> or =lambda(min) (2) of the inertia tensor. We present a
      systematic finite size scaling analysis of the radius of gyration and the
      eigenvalues of the inertia tensor at different phases of the observed folding
      transitions. In the high-temperature flat phase, the radius of gyration R(g)
      grows with the linear size of the membrane L as R(g) proportional to L(nu), where
      the exponent nu is approximately equal to 1.0. The eigenvalues of the inertia
      tensor scale as lambda(max) proportional to lambda(med) proportional to L(nu) and
      lambda(min) proportional to L(nu(min) ), whereby the roughness exponent nu(min)
      is approximately equal to 0.7. We also find that the time tau(R) of a self
      avoiding membrane to diffuse a distance R(g) scales as tau(R) proportional to
      L(2nu+2), which is in good agreement with the theoretical predictions.

PMID- 18035905
TI  - Packing structures of single-stranded DNA and double-stranded DNA thiolates on
      Au(111): a molecular simulation study.
AB  - The packing structures of single-stranded DNA (ssDNA) and double-stranded DNA
      (dsDNA) thiolates on implicit gold surfaces were studied in explicit aqueous
      solutions of 1M NaCl using molecular dynamics simulations. The simulations were
      based on individual DNA chains placed in hexagonal simulation boxes of different
      sizes, representing various packing densities. The total potential energy per DNA
      chain was compared. The optimal packing structures were determined based on the
      minimal potential energy within the limits of the conditions that were evaluated
      in this study. The optimal packing density of ssDNA was found to be 0.19 DNA
      chains/nm(2), which is consistent with that determined experimentally.
      Furthermore, the optimal packing density of dsDNA was shown to be approximately
      58% of the packing density for ssDNA, indicating that the packing of ssDNA should
      be approximately 58% of its optimal packing in order to achieve the best
      hybridization.

PMID- 18035907
TI  - Comment on "Bohmian mechanics with complex action: a new trajectory-based
      formulation of quantum mechanics" [J. Chem. Phys. 125, 231103 (2006)].

PMID- 18035906
TI  - Charge state of the fast gate in chloride channels: insights from electrostatic
      calculations in a schematic model.
AB  - Fast gating is a unique property of chloride channels, where a permeating Cl(-)
      ion acts as its own ligand in opening the channel. The glutamate residue
      implicated in fast gating normally carries a unit negative charge. Whether this
      charge needs to be protonated to enable permeation of a Cl(-) ion is an important
      question that will affect how models of chloride channels are constructed. We
      investigate the energetic consequences of the charge state of this glutamate
      residue from continuum electrostatics using a schematic cylindrical channel
      model. Both analytical solutions of the Poisson equation for an infinite cylinder
      and numerical ones for a finite cylinder are employed in the calculations.

PMID- 18035909
TI  - Effects of substrate and orientational property of liquid crystal domains on the
      blood compatibility of polymer/liquid crystal composite membranes.
AB  - A series of polymer/cholesteryl liquid crystal (LC) composite membranes were
      prepared. Polyurethane and polyvinyl chloride, as a substrate, were blended with
      cholesteryl tetraethylene glycol carbonate to form composite membranes in an
      electric field under normal conditions. The blood compatibility of composite
      materials was identified by the dynamic blood-clotting test, haemolysis ratio
      measurement, platelet adhesion and SEM observation. The results showed that the
      content of LC, the ordered extent of LC domains embedded in composite materials
      and the type of substrate have greater effects on the blood compatibility of
      polymer/LC composite materials. When the LC domains were properly oriented,
      polymer/LC composite membranes had an excellent haemocompatibility, fewer
      platelets were adhered and spread and showed little distortion on the surface of
      materials.

PMID- 18035910
TI  - Discrimination and analysis of phytoplankton using a microfluidic cytometer.
AB  - Identification and analysis of phytoplankton is important for understanding the
      environmental parameters that are influenced by the oceans, including pollution
      and climate change. Phytoplanktons are studied at the single cell level using
      conventional light-field and fluorescence microscopy, but the technique is labour
      intensive. Flow cytometry enables rapid and quantitative measurements of single
      cells and is now used as an analytical tool in phytoplankton analysis. However,
      it has a number of drawbacks, including high cost and portability. We describe
      the fabrication of a microfluidic (lab-on-a-chip) device for high-speed analysis
      of single phytoplankton. The device measures fluorescence (at three wavelength
      ranges) and the electrical impedance of single particles. The system was tested
      using a mixture of three algae (Isochrysis Galbana, Rhodosorus m., Synechococcus
      sp.) and the results compared with predictions from theory and measurements using
      a commercial flow cytometer (BD FACSAria). It is shown that the microfluidic flow
      cytometer is able to distinguish and characterise these different taxa and that
      impedance spectroscopy enables measurement of phytoplankton biophysical
      properties.

PMID- 18035911
TI  - Biocompatibility study of plasma-coated nitinol (NiTi alloy) stents.
AB  - The authors aimed to assess the surface modification effects of plasma coatings
      on biocompatibility of nitinol intravascular stent in terms of anticoagulation,
      haemocytolysis rate, hydrophilicity, cytotoxicity and so on. In order to improve
      their surface adhesive properties to endothelial cells, NiTi alloy intravascular
      stents were treated and coated using a low-temperature plasma deposition
      technique. It was found that plasma coating changed the surface morphology of the
      stents to a micron-level surface roughness in the range of 1-5 microm. In
      comparison with the untreated control, the plasma-treated NiTi alloy
      intravascular stents showed increased surface hydrophilicity and enhanced
      anticoagulation property. Testing results on plasma-coated NiTi stents indicated
      that they complied with the standard of national biologic safety evaluation of
      medical apparatus and instrument (GB/T16886-1997, People's Republic of China) in
      terms of haemocytolysis rate, cytotoxicity and pyretogen.

PMID- 18035912
TI  - One-step synthesis and characterisation of chitosan-mediated micro-sized gold
      nanoplates through a thermal process.
AB  - Most of the synthesising methods of gold nanoplates reported to date rely heavily
      on the use of chemical reducing agents such as N, N-dimethylformamide, sodium
      borohydride or other organic compounds. All of these chemicals are highly
      reactive and may pose potential biological risks. A simple, convenient and
      economical route for the mass synthesis of single-crystalline, micro-sized,
      polygonal gold nanoplates using chitosan as a reducing/capping agent is reported.
      The nanoplates possess well-defined shapes with sharp edges confirmed by scanning
      electron microscopy. The gold nanoplates are single crystals bound primarily by
      (1 1 1) lattice planes, as revealed by both selected area electron diffraction
      and powder X-ray diffraction. These large gold nanoplates had strong absorption
      in the near-infrared region. The concentration and molecular weight of chitosan
      are important factors for the morphology and size control of the final product.
      This facile approach may be extended to the synthesis of some other metal
      nanostructures.

PMID- 18035913
TI  - Neonatal mortality in India.

PMID- 18035914
TI  - Where are we going with percutaneous aortic valve replacement?

PMID- 18035916
TI  - Unique dual mechanism of action of eprosartan: effects on systolic blood
      pressure, pulse pressure, risk of stroke and cognitive decline.
AB  - Hypertension is a common condition associated with considerable morbidity and
      mortality. Antihypertensive drugs reduce the risk of cardiovascular and
      cerebrovascular events, and may also be associated with reductions in cognitive
      decline. Eprosartan is an angiotensin II type 1 receptor antagonist with a unique
      dual mechanism of action that is approved for the treatment of essential
      hypertension. In clinical trials, eprosartan has been shown to significantly
      reduce systolic blood pressure and to be associated with significant reductions
      in pulse pressure in elderly patients with isolated systolic hypertension. Data
      suggest that blood pressure reductions achieved with eprosartan in elderly
      hypertensive patients are also associated with improvements in cognitive
      function. Eprosartan compares favorably with other classes of antihypertensive
      agents in terms of reductions in mortality, cardiovascular and cerebrovascular
      events, and stroke recurrence. Evidence suggests that eprosartan may represent a
      useful addition to combination drug strategies for the management of hypertensive
      patients with elevated cardiovascular and cerebrovascular risk.

PMID- 18035917
TI  - Efficacy and safety of fondaparinux in patients with acute coronary syndromes.
AB  - Fondaparinux (Arixtra, GlaxoSmithKline) is a synthetic, selective, activated
      Factor X inhibitor. On the grounds of its favorable benefit:risk ratio,
      fondaparinux is approved for the prevention and treatment of venous
      thromboembolism. Two large trials involving approximately 32,000 patients
      recently evaluated fondaparinux in the treatment of non-ST elevation acute
      coronary syndromes and ST elevation acute myocardial infarction. Fondaparinux was
      compared with enoxaparin or usual care, depending on the setting. A single, once
      daily 2.5-mg subcutaneous dose of fondaparinux was used in both studies. After a
      brief introduction to the drug, this article presents the results obtained in
      these trials with fondaparinux and compares them with those obtained with other
      anticoagulants. Overall, it appears that fondaparinux at the single, once-daily
      dose of 2.5 mg represents a valuable new alternative for the treatment of
      patients with acute coronary syndromes.

PMID- 18035918
TI  - Doxazosin in metabolically complicated hypertension.
AB  - Metabolic syndrome, a cluster of metabolic abnormalities with visceral obesity
      and insulin resistance as its central component, is highly prevalent among
      hypertensive patients. Hypertension complicated by metabolic syndrome is
      associated with an increased risk of cardiovascular disease and new-onset Type II
      diabetes mellitus that further aggravates the prognostic outlook. Such a complex
      condition requires a multifactorial intervention including blood pressure
      lowering, improvement of the adverse metabolic profile and delayed onset of new
      diabetes. In this respect, doxazosin and other alpha-1 adrenoceptor blocking
      agents are of interest given their effect on the lipid profile in dyslipidemic,
      obese hypertensive patients, either diabetic or not. Doxazosin improves insulin
      sensitivity, apparently by accelerating insulin and glucose disposal through
      vasodilatation of skeletal muscle vascular beds. Whether long-term treatment with
      the drug might delay, or possibly prevent, incident Type II diabetes in
      hypertension complicated by metabolic syndrome is an intriguing possibility to be
      tested in appropriately designed clinical trials.

PMID- 18035919
TI  - Insight into ACE inhibition in the prevention of cardiac events in stable
      coronary artery disease: the EUROPA trial.
AB  - The European Trial on Reduction of Cardiac Events with Perindopril in Stable
      Coronary Artery Disease (EUROPA) investigated the effect of angiotensin
      converting enzyme inhibition on the prevention of cardiac events in patients with
      stable coronary artery disease (CAD) without apparent heart failure. Perindopril
      8 mg/day significantly reduced a composite outcome of cardiovascular death,
      nonfatal myocardial infarction or resuscitated cardiac arrest by 20% compared
      with placebo, in addition to standard preventive therapies. This review describes
      the substudies and subpopulation analyses carried out within the EUROPA
      population, concluding that the benefits of perindopril extend to all stable CAD
      patients, even revascularized patients or those with preserved left ventricular
      function. Data on the pathophysiological mechanisms underlying CAD indicate
      direct vascular protection with perindopril. This helps explain why perindopril
      is beneficial in preventing cardiac events in stable CAD patients.

PMID- 18035920
TI  - Postinterventional medication after catheter ablation of atrial fibrillation:
      angiotensin receptor blockers or ACE inhibitors?

PMID- 18035921
TI  - Interventions for carotid artery disease: time to confront some 'inconvenient
      truths'.
AB  - The landmark randomized trials, comparing best medical therapy with carotid
      endarterectomy, in patients with symptomatic and asymptomatic carotid artery
      disease set the standard for developing evidence-based practice guidelines
      throughout the world. Accordingly, the vox populi opinion now tends to be that
      all otherwise-fit symptomatic patients with 50-90% stenoses (using the NASCET
      measurement method) and low-risk asymptomatic patients with 60-99% stenoses
      should be considered for intervention, the only debate being whether the
      intervention is surgery or angioplasty. Yet, the concept of 'one size fits all'
      is fundamentally flawed and masks a number of 'inconvenient truths'. Four of
      these are debated in this review including: the deleterious effect of delaying
      treatment in symptomatic patients, the fact that there is no 'gender equality' in
      carotid artery disease, the concept of 'high risk' has been abused, and 'low
      risk' registries are no substitute for performing randomized trials.

PMID- 18035922
TI  - Timing of operation in asymptomatic severe aortic stenosis.
AB  - Calcific aortic stenosis is now the main cause of aortic stenosis in the majority
      of patients, due to declining incidence of rheumatic fever. Risk factors such as
      hyperlipidemia play an important role in the progression of aortic stenosis.
      According to the most recent American College of Cardiology/American Heart
      Association guidelines, peak velocity greater than 4 m/sec, a mean gradient of
      more than 40 mmHg and a valve area of less than 1.0 cm(2) is considered
      hemodynamically severe aortic stenosis. Aortic valve surgery promptly should be
      done in symptomatic patients due to dismal prognosis without operation. Features
      such as high aortic valve calcium and positive exercise test identify
      asymptomatic patients who would benefit from early aortic valve surgery. Due to
      improvement in surgical techniques and better prosthesis, aortic valve surgery
      can now be offered at low risk to a selected group of asymptomatic patients with
      severe aortic stenosis. Currently percutaneous aortic valves are used in very
      high-risk patients with severe symptomatic aortic stenosis. Their role may expand
      in the future, depending on the improvements in design and operator experience.
      Whether advances in molecular cardiology lead to novel therapies in preventing
      calcific aortic stenosis in the future remains to be seen.

PMID- 18035923
TI  - Managing mechanical valves with reduced anticoagulation.
AB  - The choice of replacement heart valve has alternated many times during the past
      40 years. The reason for the change is related to the balance between prosthesis
      longevity and the need for anticoagulation therapy. Bioprosthetic valves do not
      require continuous anticoagulation therapy but their expected life can be less
      than the patient's. Anticoagulation therapy for mechanical valves carries the
      risk of bleeding or thromboembolism. Research shows progress toward a mechanical
      valve that has a reduced thrombotic risk which may reduce the anticoagulation
      therapy requirements. Patient self-management of anticoagulation therapy results
      in more effective therapy with lower doses of anticoagulants. The current trend
      is more frequent use of bioprosthetic valves; however, this trend may again
      reverse as therapy for mechanical valves is refined.

PMID- 18035924
TI  - Replacement of aortic root and ascending aorta in adult congenital heart disease.
AB  - The aortic root and ascending aorta can be involved in a wide spectrum of
      diseases; both congenital and acquired. Progressive aortic root or ascending
      aortic dilatation and aneurysmal formation can lead to serious complications,
      including aortic valve incompetence, aortic dissection and aortic rupture.
      Various medical and surgical strategies have been developed over the past few
      decades to manage and prevent such complications. In this review, congenital
      conditions of aortic dilatation will be discussed.

PMID- 18035925
TI  - Network-centered view of coronary artery disease.
AB  - Systems biology is an emerging field that attempts to examine multiple elements
      of a biologic system using techniques such as expression microarrays or
      proteomics. The goal of systems biology is to detect all the elements of a system
      and create an interaction network between these so that the system can be
      explained under specified conditions. In this review we discuss how systems-based
      approaches are being applied to cardiovascular disease, illustrating concepts,
      such as the integration of orthogonal datasets, coexpression networks and
      emergent properties.

PMID- 18035926
TI  - Pharmacogenomics in prevention of diabetic cardiovascular disease: utilization of
      the haptoglobin genotype in determining benefit from vitamin E.
AB  - Numerous large clinical trials have been carried out over the past several years
      testing the ability of the antioxidant vitamin E to prevent diabetic
      cardiovascular disease. Meta-analysis of these studies has demonstrated that
      vitamin E does not provide any cardiovascular protection and may be associated
      with an increase in mortality. However, these studies did not address possible
      benefit to subgroups with increased oxidative stress. In this review we provide
      supporting clinical evidence and a mechanistic basis for utilizing a genetic
      marker, the haptoglobin genotype, in determining whether vitamin E therapy may or
      may not be beneficial for a given patient with diabetes.

PMID- 18035927
TI  - Neurological complications of coronary angiographic procedures.
AB  - Neurological complications of coronary angiographic procedures are uncommon,
      varied and can include central nervous toxicity caused by contrast agents
      (contrast reactions), as well as ischemic and hemorrhagic stroke. These
      complications are rare; however, more recent data derived from neuroimaging
      studies suggest that there is a higher incidence of 'silent' ischemic events. The
      impact of these subclinical events is still uncertain, but a few studies suggest
      that long term they may lead to cognitive decline, which is usually subtle. The
      clinical presentation of both contrast reactions and strokes can, at times, be
      very similar as there is a higher than expected incidence of posterior
      circulation involvement with both. While the treatment of contrast reactions is
      usually supportive, treatment of ischemic stroke in patients undergoing
      catheterization procedures appears, based on limited case report series, to lead
      to favorable outcomes with immediate neuroangiographic intervention, including
      local administration of recombinant-type tissue plasminogen activator.

PMID- 18035928
TI  - Metabolic therapy for the treatment of ischemic heart disease: reality and
      expectations.
AB  - Ischemic heart disease is a major cause of morbidity and mortality in the world.
      Most of the existing therapeutic strategies used to treat ischemic heart disease
      aim at either increasing the oxygen supply to the heart (thrombolysis,
      revascularization, angiotensin converting enzyme inhibition and antiplatelet
      therapy) or decreasing the oxygen demand of the heart (beta-blockers and
      nitrates). Despite the fact that a compromised energy supply to the heart muscle
      is central to the pathology of ischemic heart disease, therapeutic approaches
      that focus on altering cardiac energy metabolism have not seen major clinical
      use. Therapeutic strategies in which the efficiency of oxygen utilization by the
      heart is enhanced could theoretically benefit the ischemic heart, and could have
      an additive benefit to existing therapeutic strategies. The energy supply for the
      heart (in the form of ATP) is normally provided by the balanced metabolism of
      both fatty acids (major part) and carbohydrates (minor part) oxidation. During
      reperfusion, this balance is broken by the dramatic enhancement of fatty acid
      oxidation and attenuation of carbohydrate oxidation, which results in
      intracellular H(+) accumulation and Ca(2+) overload. This article reviews the
      alterations in cardiac energy metabolism that occur in the ischemic heart, and
      discusses the existing and proposed pharmacologic therapies to optimize the
      balance of fatty acids and carbohydrate oxidation for the treatment of ischemic
      heart diseases.

PMID- 18035929
TI  - Contemporary clinical management of atrial septal defects in the adult.
AB  - Patients with simple congenital heart disease, such as isolated atrial septal
      defects (ASDs), are rapidly becoming a relatively large population with a variety
      of clinical problems that are often missed by pediatric physicians or grown-up
      congenital heart disease specialists and may involve different adult health
      professionals, such as general cardiologists or internists. A Medline search was
      performed to search for randomized trials, prospective cohort studies, meta
      analysis, reviews and practice guidelines regarding different aspects of ASD in
      adults over a 6 year period. Isolated ASD are common (7% of all cardiac
      anomalies) and can present at any age, sometimes in conjunction with other
      genetic disorders such as Down syndrome or in a familiar form. The diagnosis is
      often accidental: Doppler echocardiography and, more recently, MRI are mandatory
      to assess types and significance of ASDs. Surgical or percutaneous repair should
      be offered at any age unless associated with pulmonary vascular disease:
      percutaneous closure should be preferred in isolated secundum ASD with sufficient
      rims on transesophageal echocardiography, whereas surgery remains the only option
      for primum and sinus defects. Follow-up of operated patients is based on Holter
      ECG and echocardiography, which should be scheduled every 2 years for secundum
      and sinus defects and every year for primum defect with valve repair. ASDs in
      adolescents and adults may be suspected in any physician's office and doctors
      should be acquainted with innovative imaging techniques and contemporary
      therapeutic options in order to deliver proper care to different types of ASDs
      and assist them after repair with appropriate follow-up strategies.

PMID- 18035930
TI  - Antegrade or retrograde cerebral perfusion as an adjunct during hypothermic
      circulatory arrest for aortic arch surgery.
AB  - Surgery of the aortic arch is a great challenge in cardiovascular surgery. Its
      partial or total replacement demands the temporary interruption of normal
      cerebral perfusion, with associated potential for neurological injury. Three
      methods of cerebral protection have been applied between 1975 and today:
      hypothermic circulatory arrest as a basic method, either alone or with antegrade
      cerebral perfusion (ACP), or retrograde cerebral perfusion (RCP) as an adjunctive
      method. After extensive research regarding the controversies that surround the
      ideal method of cerebral protection, it is obvious that ACP is superior to RCP
      for brain protection. ACP obtains a near-physiologic brain perfusion, with
      homogenous distribution of blood throughout the capillary beds, and extends the
      safe time of hypothermic circulatory arrest to 80 min, allowing the completion of
      whatever aortic arch work is necessary. By contrast, RCP perfuses a smaller brain
      territory than ACP, approximately 10-20%. Hence, RCP is, in our opinion, a
      'smaller adjunct' to brain protection than ACP. Detailed evidence and future
      directions for further research are discussed.

PMID- 18035932
TI  - Molecular insights into the microvascular regulation of lymph formation.

PMID- 18035933
TI  - Dynamic imaging of lymphatic vessels and lymph nodes using a bimodal
      nanoparticulate contrast agent.
AB  - BACKGROUND: Evaluation of lymphedema and lymph node metastasis in humans has
      relied primarily on invasive or radioactive modalities. While noninvasive
      technologies such as magnetic resonance imaging (MRI) offer the potential for
      true three-dimensional imaging of lymphatic structures, invasive modalities, such
      as optical fluorescence microscopy, provide higher resolution and clearer
      delineation of both lymph nodes and lymphatic vessels. Thus, contrast agents that
      image lymphatic vessels and lymph nodes by both fluorescence and MRI may further
      enhance our understanding of the structure and function of the lymphatic system.
      Recent applications of bimodal (fluorescence and MR) contrast agents in mice have
      not achieved clear visualization of lymphatic vessels and nodes. Here the authors
      describe the development of a nanoparticulate contrast agent that is taken up by
      lymphatic vessels to draining lymph nodes and detected by both modalities.
      METHODS: A unique nanoparticulate contrast agent composed of a polyamidoamine
      dendrimer core conjugated to paramagnetic contrast agents and fluorescent probes
      was synthesized. Anesthetized mice were injected with the nanoparticulates in the
      hind footpads and imaged by MR and fluorescence microscopy. High resolution MR
      and fluorescence images were obtained and compared to traditional techniques for
      lymphatic visualization using Evans blue dye. RESULTS: Lymph nodes and lymphatic
      vessels were clearly observed by both MRI and fluorescence microscopy using the
      bimodal nanoparticulate contrast agent. Characteristic tail-lymphatics were also
      visualized by both modalities. Contrast imaging yielded a higher resolution than
      the traditional method employing Evans blue dye. MR data correlated with
      fluorescence and Evans blue dye imaging. CONCLUSION: A bimodal nanoparticulate
      contrast agent facilitates the visualization of lymphatic vessels and lymph nodes
      by both fluorescence microscopy and MRI with strong correlation between the two
      modalities. This agent may translate to applications such as the assessment of
      malignancy and lymphedema in humans and the evaluation of lymphatic vessel
      function and morphology in animal models.

PMID- 18035935
TI  - Clinical outcomes in lymphocytopenic lymphatic malformation patients.
AB  - BACKGROUND: To determine if lymphocytopenia in patients with lymphatic
      malformation (LM) is associated with rates of infection and poor clinical
      outcomes. MATERIALS AND METHODS: This is a retrospective case series at a
      tertiary pediatric hospital, of 21 consecutive patients (11 male and 10 female)
      undergoing LM treatment. Clinical data (i.e., age, clinical LM stage, presence of
      tissue hypertrophy, frequency/type of medical therapy, and number of
      hospitalizations) obtained from LM patients with lymphocytopenia (n = 6) was
      compared to LM patients without lymphocytopenia (n = 15). RESULTS: The average
      age at the time of detailed leukocyte analysis was 67 months (Range 1-231). Six
      patients with lymphocytopenia (below 1500/cm(3)) were compared with 15 without
      lymphocytopenia (above 1500/cm(3)). All six patients with lymphocytopenia had
      large bilateral LM and normal neutrophil and platelet counts. The total number of
      hospital admissions was two times greater in lymphocytopenic patients (mean 8.3)
      compared to nonlymphocytopenic patients (mean 4.09) Chi square analysis revealed
      a statistical difference in lymphocytopenic patients. They were more likely to
      have had central line placement, central line infection, bacteremia, prophylactic
      antibiotics, admission at birth, infections distant from the lymphatic
      malformation and a treatment complication compared to nonlymphocytopenic
      patients. Univariate logistic regression revealed that, independent of LM stage,
      the use of prophylactic antibiotics, the need for a central line, the occurrence
      of a line infection, and the hospital admission rate were significantly increased
      in lymphocytopenic patients. CONCLUSION: Patients with LM-associated
      lymphocytopenia have increased hospitalization requirements, rate of infection,
      and receive more intensive antibiotic therapy compared to nonlymphocytopenic LM
      patients.

PMID- 18035934
TI  - Terminal lymphatics: the potential "lethal corner" in the distribution of tissue
      pO2.
AB  - BACKGROUND: Terminal lymphatic fluid is the compartment furthest removed from the
      oxygen supply, and therefore should present the lowest pO(2) in the tissue due to
      oxygen consumption by the tissue and the lymphatic vessel wall. METHODS AND
      RESULTS: The distribution of pO(2) was determined in the tissue, the lymphatic
      microvessels, and arterioles and venules of the hamster chamber window model,
      which is studied without anesthesia with the tissue isolated from the
      environment. Lymphatic fluid pO(2) was measured with the phosphorescence oxygen
      quenching method. Small terminal lymphatic fluid pO(2) was 18.4 +/- 2.6 mmHg, and
      18.0 +/- 2.4 mmHg in collecting lymphatics. Tissue pO(2) averaged 24.6 +/- 2.7
      mmHg. The significant difference between tissue and intralymphatic pO(2) was due
      in part to the presence of an oxygen gradient across the lymphatic wall, which
      ranged from 3.7 +/- 1.3 mmHg for terminal lymphatics, to 6.0 +/- 1.2 mmHg for
      collecting lymphatics. This gradient is assumed to be due to the oxygen
      consumption by the cellular component of the lymphatic wall. CONCLUSION: The
      increased vessels wall gradient found in collecting lymphatics was reconciled by
      the findings that these microlymphatic vessels tend to be contiguous to the
      arterioles, whereas the terminal lymphatics are dispersed in the tissue. These
      findings indicate that terminal lymphatic present the lowest oxygen tension in
      the tissue, and therefore are the locations at risk to develop anoxia when the
      microvascular oxygen supply becomes limited.

PMID- 18035936
TI  - Prognostic significance of cell proliferation and apoptosis-regulating proteins
      in Epstein-Barr virus positive and negative pediatric Hodgkin lymphoma.
AB  - Apoptosis-related genes and proteins and proliferation activity and their
      relationship with Epstein-Barr virus (EBV) is a contemporary issue. In this
      study, prognostic or pathogenetic roles of EBV latent infection, proliferating
      activity, and apoptosis-regulating proteins in pediatric Hodgkin lymphomas were
      explored. EBV-EBER, lmp-1, ki-67, bcl-2, survivin, Bax, fas, c-myc, and p53, and
      apoptotic index were analyzed in 63 pediatric Hodgkin lymphoma cases. The results
      were evaluated by chi-square, Mann Whitney U test, Pearson correlation analysis,
      and Kaplan Meier survival analysis. Thirty-two cases were stage I or II, whereas
      31 cases were stage III or IV. The mean age was 8.4 +/- 63.54 years. EBV was
      positive in 52 (82.5%) cases. Overall survival was 94% and event-free survival
      83.6%. Bax expression was observed 74.6%, bcl-2 47.6%, survivin 43%, p53 33.3%,
      fas 54%, and c-myc 25.4%. The mean apoptotic index was 18.22%. The mean
      proliferation index was 57.83%. The proliferation index was positively related
      with EBV but not with prognosis. None of the parameters were related with
      prognosis. EBV was negatively related with the apoptotic index. There were no
      relationships between bax, bcl-2, survivin, p53, fas, and c-myc with EBV. These
      results suggest that EBV might play a role in Hodgkin lymphoma pathogenesis by
      inducing proliferative activity and inhibiting apoptosis. Apoptosis-related
      proteins were not correlated with EBV. None of the parameters was found to
      predict prognosis.

PMID- 18035938
TI  - Literature watch. Dellinger, MT, RJ Hunter, et al. (2007). Chy-3 mice are Vegfc
      haploinsufficient and exhibit defective dermal superficial to deep lymphatic
      transition and dermal lymphatic hypoplasia. Dev Dyn 236:2346-2355.

PMID- 18035937
TI  - Clinical assessment of human lymph flow using removal rate constants of
      interstitial macromolecules: a critical review of lymphoscintigraphy.
AB  - Edema is a common clinical problem, and the daily avoidance of edema depends
      critically on the lymphatic system, which clears leaked plasma proteins and fluid
      from the interstitial compartment. There is often confusion as to the difference
      between chronic edema and lymphedema. Lymphedema is by definition primarily a
      disease of impaired lymphatic drainage and lymph flow, and progress in lymphedema
      research, currently an increasingly active field, requires a clinically viable
      method for the quantitative assessment of lymph drainage rate in patients.
      Measurement of the rate of clearance of a new protein marker, radiolabelled human
      immunoglobulin, from skin, subcutis, and muscle provides a way of measuring human
      lymph flow quantitatively and is the only viable clinical method currently
      available. Considerable strides have been made over the last 5-10 years in
      evaluating the method and its pitfalls, including potential complications such as
      vascular clearance, peripheral lymphovenous communications and label
      dissociation. The review assesses critically, for the first time, the evidence
      relating to the method: its pitfalls; human lymph flow in various healthy and
      oedematous tissues; and how this is altered in hyperfiltration edemas,
      inflammation, vasoconstriction and various primary and secondary human
      lymphedemas.

PMID- 18035940
TI  - Barriers for medical devices for the developing world.

PMID- 18035941
TI  - Progress in the development of neural prosthetic devices.

PMID- 18035942
TI  - Assisted circulation: experience with the Novacor Left Ventricular Assist System.
AB  - Surgical therapy for the treatment of heart failure is a relatively young
      solution to a problem that has overwhelmed civilizations dating back to the First
      Dynasty. Despite centuries of enormous multidisciplinary medical and
      technological advance, nearly 2000 people in the USA died of cardiovascular
      disease every day in 2006, averaging one death every 35 seconds, and claiming
      more lives than the next four leading causes of death combined. In 2007, one in
      30 female deaths will be from breast cancer, while one in 2.6 will be from
      cardiovascular disease. The prevalence of heart failure in our population is a
      staggering 5 million in the USA and 6.5 million in Europe per year. Furthermore,
      based on the 44-year follow-up of the National Heart, Blood, and Lungs Institute
      Framingham Heart Study, 80% of men and 70% of women under the age of 65 years who
      have heart failure will die within 8 years. The focus of this article will be to
      review the history and future of the Novacor Left Ventricular Assist System as it
      relates to the failing heart; the story of how the innovator, the researcher, the
      engineer and the surgeon have come together to offer a surgical solution to a
      medical problem of inconceivable scope.

PMID- 18035943
TI  - OptiVol fluid status monitoring with an implantable cardiac device: a heart
      failure management system.
AB  - Early intervention and prevention of hospitalizations would reduce the burden of
      heart failure on the healthcare system while improving the quality of life of
      affected patients. Traditional methods of patient assessment, including physical
      examination and patient report of symptoms, have a low sensitivity for detecting
      elevations in left ventricular filling pressure, a major precursor of pulmonary
      congestion and heart failure decompensation. Intrathoracic fluid accumulation
      during pulmonary congestion leads to decreased impedance across the lung. The
      OptiVol system in the InSync Sentrycardiac resynchronization therapy
      defibrillator, Concerto cardiac resynchronization therapy-defibrillator and
      Virtuoso implantable cardioverter-defibrillator devices monitors intrathoracic
      impedance and is intended to recognize early signs of volume accumulation before
      physical symptoms appear. Through a recent clinical trial, the default setting
      for the OptiVol system functioned as a predictor of hospitalization with 76.9%
      sensitivity. Intrathoracic impedance monitoring is not intended to replace
      careful frequent clinical evaluation of the heart failure patient, but instead
      aims to complement traditional heart failure management practices.

PMID- 18035944
TI  - BioSTAR bioabsorbable septal repair implant.
AB  - Thousands of patients have had congenital defects of their intra-atrial septa
      successfully closed via percutaneous techniques in the cardiac catheterization
      laboratory for hemodynamic correction, stroke, migraine and decompression
      illness. However, currently available closure technologies leave a permanent
      cardiac implant in a relatively young patient population. As the first device
      incorporating a bioabsorbable material for the treatment of structural heart
      disease, BioSTAR is uniquely designed to remodel into native tissue following
      closure, providing a more natural method of defect repair. This paper reviews
      atrial morphology, with a focus on patent foramen ovale, indications both present
      and emerging, and the development of technologies that promote a healthy natural
      healing response, with a focus on the design, testing and clinical experience
      with BioSTAR.

PMID- 18035945
TI  - HumaPen Memoir: a novel insulin-injecting pen with a dose-memory feature.
AB  - Optimizing glycemic control may help to reduce the risks of diabetes
      complications, but it is often difficult to achieve, partly owing to poor
      treatment adherence. One barrier to adherence is forgetfulness. The HumaPen
      Memoir pen is the only electronic reusable insulin pen with a multiple-dose
      memory feature. This enables the device to store information regarding dates and
      times of the previous 16 doses of insulin, including priming doses. The pen has a
      digital display and a two-way dial to minimize waste of insulin. The digital
      display facilitates accurate dose selection. Both patients and healthcare
      providers rate as important the pen's ability to confirm administered doses and
      times, its overall ease of injection and display readability, and its minimal
      waste when adjusting dose settings.

PMID- 18035947
TI  - Automated syringe driver for acupoint injection in functional MRI studies: a case
      for quantified point injection in neuroimaging studies of acupuncture.
AB  - The investigation of proposed acupuncture models is experiencing increasing
      interest particularly since the inception of functional neuroimaging in the early
      1990s, but difficulty in providing acceptable controls has been an ongoing
      limitation. The use of titrated stimulation to generate a dose response is
      implied in the nature of the stimulus and the timing of the response. To address
      the complexity of delivering an accurate stimulus during an imaging study while
      simultaneously maintaining synchrony and recording stimulus parameters, stimulus
      delivery needs to be an automated task. This report presents the design and
      general description of a system capable of delivering acupoint stimulation by
      injection of precisely timed and measured saline doses while simultaneously
      interfaced to biomonitoring or neuroimaging instruments. The results of
      instrument validation in a clinical environment are presented, along with a
      discussion of the usefulness and limitations of the device.

PMID- 18035946
TI  - Image-guided thermal ablation of nonresectable hepatic tumors using the Cool-Tip
      radiofrequency ablation system.
AB  - Percutaneous thermal ablation techniques have gained considerable attention as an
      alternative to surgery for the treatment of malignant liver tumors in selected
      patients. In particular, image-guided radiofrequency ablation (RFA) is
      increasingly being used for the local treatment of hepatocellular carcinoma, as
      well as for metastases to the liver. As a minimally invasive treatment option,
      this technique has several advantages compared with surgical resection. Benefits
      include reduction in morbidity and mortality, lower cost, suitability for real
      time imaging guidance, use in an outpatient setting and use in patients who are
      not surgical candidates. The Cool-Tip RFA system has recently received US FDA
      approval for use in ablating nonresectable liver tumors. This article describes
      the principles and application of radiofrequency ablation for the treatment of
      nonresectable hepatic tumors along with the unique features of the Cool-Tip RFA
      system. Finally, a view into the future suggests that, as the trend towards
      minimally invasive treatment options for hepatic malignancies continues, RFA will
      assume increasing clinical application.

PMID- 18035949
TI  - New technologies to evaluate esophageal function.
AB  - This review provides an overview of the recent advances made in diagnostic
      technologies of esophageal functional disorders. There is discussion of
      technologies that evaluate esophageal motor function with special attention to
      high-resolution manometry and esophageal manometry combined with intraluminal
      impedance testing. Technologies to evaluate gastroesophageal reflux disease are
      presented with focus on 24-h ambulatory pH monitoring with intraluminal impedance
      testing and 48-h ambulatory catheter-free pH monitoring. These new technologies
      have advanced the study and treatment of esophageal disorders in that they allow
      for more accurate diagnosis of known esophageal disorders and have introduced
      previously unexplored disorders, such as achalasia with shortening of the
      esophagus and nonacid reflux.

PMID- 18035948
TI  - Compression gastrointestinal anastomosis.
AB  - The creation of anastomoses between various parts of the GI tract is a major task
      in the daily practice of oncological, reconstructive and transplant surgery. The
      most widely used anastomosing techniques today involve the use of sutures or
      metal titanium staples. Both techniques involve foreign material penetrating the
      tissue and evoking localized inflammatory response, tissue injury and breaking of
      mucosal barriers that may facilitate bacterial growth within the anastomotic
      line, increasing the propensity to anastomotic-related morbidity. Different types
      of compression devices were successfully used clinically in the past. The history
      and evolving characteristics of this technology is reviewed. Nitinol-based
      solutions for the creation of compression anastomosis are evaluated as a possible
      potential for revolutionary impact on the current surgical methods and
      anastomosing technology in the alimentary tract and beyond.

PMID- 18035950
TI  - Sorbent-based artificial liver devices: principles of operation, chemical effects
      and clinical results.
AB  - Devices for support of patients with liver failure are of two types:
      bioartificial livers and artificial livers. Bioartificial livers include
      hepatocytes in bioreactors to provide both excretory and synthetic liver
      functions. Artificial livers use nonliving components to remove toxins of liver
      failure, supply nutrients and macromolecules. Current artificial liver devices
      use columns or suspensions of sorbents (including adsorbents and absorbents) to
      selectively remove toxins and regenerate dialysate, albumin-containing dialysate,
      plasma filtrate or plasma. This article reviews three artificial liver devices.
      Liver Dialysis uses a suspension of charcoal and cation exchangers to regenerate
      dialysate. MARS uses charcoal and an anion exchanger to regenerate dialysate with
      albumin. Prometheus uses neutral and anion exchange resins to regenerate a plasma
      filtrate containing albumin and small globulins. We review the operating
      principles, chemical effects, clinical effects and complications of use of each
      type of artificial liver. These devices clearly improve the clinical condition of
      patients with acute or acute-on-chronic liver failure. Further randomized outcome
      studies are necessary to prove clinical outcome benefit of the artificial liver
      support devices, and define what types of patients appear most amenable to
      therapy.

PMID- 18035951
TI  - Confocal endomicroscopy: a novel imaging technique for in vivo histology of
      cervical intraepithelial neoplasia.
AB  - Optical imaging technologies, such as reflectance and fluorescence spectroscopy,
      have shown the potential to provide enhanced detection of changes in the uterine
      cervix at clinical examination. This review focuses on fluorescence confocal
      endomicroscopy that enables in vivo microscopic imaging of the cervical
      epithelium in histological detail in real time. The microscopic imaging technique
      may permit 'see-and-treat' workflows in colposcopy through high-resolution
      fluorescence imaging of cellular and subcellular detail from the surface and
      subepithelial layers of the cervical mucosa. The device may be used in
      conjunction with a conventional colposcope. Preliminary data from clinical
      studies suggest that the device can be used to visualize features of the cervical
      epithelium including the squamo-columnar junction, dermal papillae and
      endocervical glands. Moreover, the technique has the ability to detect and grade
      precancerous changes of the cervical epithelium in conditions, such as cervical
      intraepithelial neoplasia, where prediction using colposcopy may be problematic.
      The early detection and diagnosis of gynecological abnormalities through the
      collection of 'optical' biopsies or targeted mucosal excisional biopsies have the
      potential to improve patient management through early therapeutic intervention
      and 'see-and-treat' strategies.

PMID- 18035952
TI  - Outcomes-based evaluations supporting computer-assisted surgery and minimally
      invasive surgery for total hip arthroplasty.
AB  - Minimally invasive surgeries, as well as computer-assisted surgery for total hip
      replacement have gained popularity over recent years. This article provides an
      overview of state-of-the-art minimally invasive surgery (MIS) and computer
      assisted surgery for total hip arthroplasty. A comprehensive review of the
      literature for scientific evidence supporting the use of these technologies was
      undertaken. This review evaluates whether commonly asked questions concerning
      these topics have been addressed. Controversy remains as to whether there are
      significant benefits of MIS or computer-assisted surgery for total hip
      arthroplasty. Fortunately, most studies report similar outcomes for both
      technologies. Minimally invasive techniques have been developed that do not
      significantly increase operative time or immediate postoperative complications.
      Computer-assisted navigation has shown improved radiographic alignment for total
      hip arthroplasty and may allow MIS to be performed more optimally. The authors
      believe that both of these technologies are likely to have a place in the future
      for hip arthroplasty with expectations of increased successful outcomes with
      these techniques while lowering complications and costs. Long-term outcomes of
      both techniques will need to be investigated.

PMID- 18035953
TI  - Robotic and magnetic navigation for atrial fibrillation ablation. How and why?
AB  - Catheter ablation techniques for atrial fibrillation are evolving with targets
      for radiofrequency ablation of atrial fibrillation increasingly being selected
      based on anatomic considerations. Such anatomic ablation techniques require
      precise catheter localization and stable contact during ablation. Even
      experienced electrophysiologists occasionally encounter difficulties in
      maintaining stable catheter contact, especially in some regions of complex
      anatomy where catheter stability is crucial. Limitations of manually deflected
      conventional ablation catheters in performing complex catheter maneuvers may also
      contribute to these challenges. The CARTO RMT version 8 has been recently
      released to guide left atrial mapping and ablation in conjunction with the
      Stereotaxis system for remote control of the ablation catheter. We aim to
      describe how this system works and why it is needed in the field of catheter
      ablation.

PMID- 18035954
TI  - What the future holds for deep brain stimulation.
AB  - For 20 years, deep brain stimulation (DBS) at high frequency has been developed
      as a substitute for the classical lesioning methods previously used in
      stereotactic and functional neurosurgery. This method has proven its efficacy,
      based on its reversibility and adaptability: two factors that are responsible for
      low morbidity. The method has been initially developed for and applied to
      movement disorders in several target areas; such as the thalamus, the pallidum
      and the subthalamic nucleus. It has now also been extended to other indications,
      such as epilepsy, dystonias and cluster headache and, more recently, to
      psychiatric disorders, such as obsessive-compulsive disorder, Gilles de la
      Tourette tics and depression. Several other disorders are currently under
      investigation and these may become new indications in the future. The mechanism
      of action is likely to be complex; associating cell-firing inhibition,
      neurotransmitter depletion, jamming and excitation of inhibitory pathways that
      lead to functional inhibition, mimicking the effects of lesioning of the
      stimulated structures. High-frequency stimulation of the subthalamic nucleus
      induces neuroprotection in animal models but has not yet been demonstrated in
      human patients suffering from Parkinson's disease. Technological development will
      enhance and refine the effects of high-frequency stimulation, and allow further
      extension of this method to new targets and new indications.

PMID- 18035955
TI  - Patient-controlled intravenous analgesia with remifentanil in nulliparous
      subjects in labor.
AB  - OBJECTIVE: in this study we controlled the efficiency and safety of using
      remifentanil combined with two different supplementary background infusions for
      labor analgesia in nulliparous patients. RESEARCH DESIGN AND METHODS: 60 subjects
      were allocated to two groups. After programming the patient-controlled analgesia
      device to deliver a fixed load and demand doses of intravenous remifentanil for
      all subjects, group r (n = 30) received a background infusion of remifentanil 0.1
      microg/kg/min and group R (n = 30) received a supplementary infusion of
      remifentanil 0.15 microg/kg/min. Visual analogue scale for analgesia, hemodynamic
      parameters, sedation scales and fetal heart rates were recorded at the 5th, 10th,
      20th and 30th min of the study and measurements continued every 15 min during 90
      min of labor and delivery. Side effects, Apgar and satisfaction scores were
      obtained for every subject. RESULTS: visual analogue scale scores of group R were
      significantly lower than those of group r throughout labor and delivery (p <
      0.05). Hemodynamic parameters and fetal heart rates of the two groups were not
      different (p > 0.05). Most subjects were awake and only nausea was obtained (p >
      0.05). The increase in the Apgar and satisfaction scores was not statistically
      significant (p > 0.05). CONCLUSION: it was determined that remifentanil with a 15
      mug demand dose and 0.15 mug/kg/min supplementary continuous infusion is an
      effective choice for patient-controlled analgesia during labor in nulliparous
      subjects.

PMID- 18035956
TI  - Therapeutic management of acute intracerebral haemorrhage.
AB  - Intracerebral haemorrhage (ICH) is a stroke resulting from spontaneous rupture of
      an intracranial vessel and is associated with high early mortality and long-term
      morbidity rates. With the exception of dedicated stroke units or neurocritical
      care, no surgical or medical intervention has been proven to effectively improve
      outcome following ICH. Pharmacotherapeutic considerations include optimal blood
      pressure control and the choice of antihypertensive agents. Acute haematoma
      expansion represents the most obvious acute treatment target. The use of
      haemostatic agents may have a role in ICH management; although it appears
      improved patient selection may be required before the use of these agents can be
      demonstrated clinically. In patients with anticoagulant-associated ICH, a number
      of therapeutic agents may be used to urgently reverse the coagulopathy, although
      further clinical trials are required. Recurrent bleeding and future thrombo
      embolic event rates in patients who require anticoagulation following ICH risks
      are difficult to determine accurately, although risk stratification data are
      emerging. This article reviews the pathophysiology, natural history and the
      evidence supporting present therapeutic management practices for ICH. The
      authors' practice based on best available evidence is provided.

PMID- 18035957
TI  - Healthcare-associated pneumonia: principles and emerging concepts on management.
AB  - Healthcare-associated pneumonia (HCAP) is a relatively new entity that includes
      pneumonia occurring in healthcare settings other than acute-care hospitals. Many
      patients with HCAP are at greater risk for colonization and infection with multi
      drug resistant (MDR) bacteria such as Pseudomonas aeruginosa, Gram-negative
      bacilli-producing extended-spectrum beta-lactamases and methicillin-resistant
      Staphylococcus aureus. Infections with these MDR pathogens require different
      empiric antibiotic therapy. To avoid initiation of inappropriate antibiotic
      therapy that may result in poorer patient outcomes, new principles for HCAP
      management were outlined in the 2005 American Thoracic Society and Infectious
      Diseases Society of America guidelines. These guidelines were suggested for
      patients assessed in acute-care hospitals and clinics, and may not be applicable
      for all patients with suspected HCAP in nursing homes and other long-term care
      settings. This review article addresses HCAP management strategies in both
      clinical settings.

PMID- 18035958
TI  - Management of glioblastoma.
AB  - Glioblastoma multiforme (GBM) are among the most devastating neoplasms claiming
      the lives of patients within a median of 1 year after diagnosis. Treatment of GBM
      requires a multidisciplinary approach. Treatments include surgery, radiotherapy,
      chemotherapy and so on. Temozolomide (TMZ) has emerged as an active agent against
      malignant gliomas. On the basis of the work by the European Organisation for
      Research and Treatment of Cancer/National Cancer Institute of Canada, concurrent
      radiotherapy and the oral alkylating agent TMZ followed by adjuvant TMZ has
      become the standard of care for patients with newly diagnosed GBM, although the
      methylation status of the O(6)-mehylguanine-DNA methyltransferase promoter is
      predictive for survival of GBM patients. Gliadel is a biodegradable polymer wafer
      impregnated with carmustine. Gliadel has been one of the few treatment modalities
      to demonstrate a statistical benefit in patients with malignant glioma. These new
      FDA approved drugs advanced the treatment of malignant glioma, but more progress
      is needed. Patients require improvements in chemotherapy, surgery, radiotherapy,
      molecular targeted therapy, immunotoxin using the convection-enhanced delivery
      and more.

PMID- 18035959
TI  - Prevention of Type 2 diabetes: fact or fiction?
AB  - The growing prevalence of Type 2 diabetes with its high morbidity and excess
      mortality is imposing a heavy burden on healthcare systems. Because of the
      magnitude of the problem, obviating diabetes has been a long-standing dream. In
      the last decade, a number of intervention strategies have been shown to be
      effective for the prevention of diabetes in high-risk populations with
      prediabetes. Seven studies have now confirmed that lifestyle modifications,
      including weight-reducing diets and exercise programs, are very effective in
      precluding or delaying Type 2 diabetes in high-risk populations with impaired
      glucose tolerance (IGT). Two major trials are the Diabetes Prevention Study (n =
      522) from Finland and the Diabetes Prevention Program (n = 3234) from the US.
      Both studies have shown that intensive lifestyle intervention could reduce the
      progression of IGT to diabetes by 58%. Furthermore, four currently-available
      drugs have been established as being effective in preventing diabetes in subjects
      with prediabetes. The Diabetes Prevention Program revealed that metformin 850 mg
      b.i.d. reduced the risk of diabetes by 31%. The STOP-NIDDM (Study To Prevent Non
      Insulin-Dependent Diabetes Mellitus) trial (n = 1429) showed that acarbose 100 mg
      t.i.d. with meals decreased the incidence of diabetes by 36% when the diagnosis
      was based on 2 oral glucose tolerance tests. The XENDOS (Xenical in the
      Prevention of Diabetes in Obese Subjects) study examined the use of orlistat, an
      antiobesity drug, as an adjunct to an intensive lifestyle modification program in
      obese non-diabetic subjects. Orlistat treatment resulted in a 37% decline in the
      development of diabetes. More recently, the DREAM (Diabetes Reduction Assessment
      with Ramipril and Rosiglitazone Medication) study (n = 5269) demonstrated that
      rosiglitazone at 8 mg once/day in subjects with prediabetes (IGT and/or impaired
      fasting glucose) was effective in reducing the risk of diabetes by 60%. It can be
      concluded that Type 2 diabetes can be prevented or delayed through lifestyle
      modifications and/or pharmacologic interventions. This is a fact.

PMID- 18035960
TI  - Latest treatment strategies for membranous nephropathy.
AB  - Thirty to forty percent of patients with idiopathic membranous nephropathy have
      persistent heavy proteinuria and may progress to end-stage kidney disease in 5 -
      15 years. The ideal treatment for these patients is a matter of debate. Several
      nonspecific immunosuppressive regimens have been suggested with the aim of
      reducing proteinuria and to improve outcome, but all are burdened by significant
      toxicity. Therefore, more specific and less toxic therapies are needed. Promising
      results have been recently obtained with rituximab, a monoclonal antibody against
      the CD20 antigen of B lymphocytes that is able to deplete these cells and, thus,
      neoformation of pathogenetic antibodies. Other novel drugs, such as
      adrenocorticotropic hormone, mycophenolate mofetil and eculizumab have been
      proposed. This paper reviews the safety/efficacy profile of various agents that
      have been proposed as therapy for this disease, with particular focus on the
      latest, more specific and hypothesis-driven approaches.

PMID- 18035961
TI  - The use of plasma-derived C1 inhibitor in the treatment of hereditary angioedema.
AB  - C1-inhibitor (C1-INH) deficiency is the genetic defect underlying hereditary
      angioedema (HAE). Subjects with HAE suffer from recurrent angioedema that may
      result in death when it affects the larynx, severe abdominal pain when it affects
      the gastrointestinal mucosa and disfiguration when it affects the skin. The use
      of plasma-derived C1-INH concentrates to revert angioedema in HAE patients
      started in the 1970s. Since that time, three different preparations arrived onto
      the market, two of them are still present. Controlled studies and a large
      clinical experience indicate that C1-INH concentrate should be considered the
      treatment of choice for disabling angioedema attacks at any site. Efficacy has
      also been shown in preventing angioedema induced by invasive medical manoeuvres.
      Limited experience with repeated weekly infusions indicates that C1-INH can be
      used for long-term prophylaxis in selected patients. The safety profile is
      excellent and there are no reports of transmission of viral infections with the
      preparations available at present. C1-INH is licensed only in a limited number of
      countries. Clinical trials are ongoing at present to expand registration.

PMID- 18035962
TI  - Pharmacotherapy for bronchiectasis.
AB  - Bronchiectasis is a chronic lung disease and clinically is characterised by
      chronic cough, sputum production and susceptibility to lower respiratory tract
      infections. Management of bronchiectasis involves investigation to identify
      treatable causes and then focusing on prevention of exacerbations by regular
      physiotherapy and the appropriate use of antibiotics for infective exacerbations.
      There are few good quality, randomised, controlled trials in bronchiectasis and
      much of the treatment is based on expert opinion and extrapolation from the
      management of other respiratory conditions. This article discusses the management
      of bronchiectasis with particular reference to the pathophysiological processes
      involved in the condition. It then looks at the available evidence supporting
      such a management plan.

PMID- 18035963
TI  - beta-Adrenergic receptor polymorphisms: relationship to the beta-agonist
      controversy and clinical implications.
AB  - Aspects of the 'beta-agonist controversy' have recently re-emerged with the
      publication of data implicating the long-acting beta-agonist salmeterol in
      increased mortality from asthma. The reasons underlying the adverse effects of
      beta2-agonists as a class are unclear. Polymorphisms of the beta2 adrenoceptor
      (ADRB2), notably the variant associated with an arginine moiety at position 16 of
      the ADRB2 protein result in changes in in vitro receptor function. There is now
      consistent clinical evidence showing that, in vivo, patients with asthma
      harbouring the Arg-16 genotype may experience reduced lung function and an
      increased frequency of exacerbations when treated with regular short-acting beta
      agonists. This may, in part, explain why beta-agonists have been associated with
      adverse outcomes in the past. ADRB2 genotyping of patients with severe or
      difficult-to-control asthma may shed light on a possible contributor to their
      clinical instability.

PMID- 18035964
TI  - Appropriate treatment for asymptomatic papillary microcarcinoma of the thyroid.
AB  - Since the 1990 s, asymptomatic papillary microcarcinoma (PMC), papillary
      carcinoma measuring <or= 1.0 cm, has frequently been detected using
      ultrasonographic screening and diagnosed by ultrasonography-guided fineneedle
      aspiration biopsy. Thyroid carcinoma was detected in 3.5% of otherwise healthy
      women aged >or= 30 years of age and most of these patients had lesions measuring
      <or= 1.5 cm in diameter, which is not discrepant with previous autopsy findings
      that latent PMC showed a high incidence. A recent observation trial showed that
      only 6.7% of low-risk PMC definitely became enlarged during 5 years of follow up,
      indicating that observation is an attractive alternative to surgery for PMC.
      However, PMC with clinically apparent metastasis detected on imaging is likely to
      show a recurrence to the lymph node and careful neck dissection as well as total
      thyroidectomy may be required. If surgical treatment is performed for low-risk
      PMC, prophylactic modified radical neck dissection is not necessary and lobectomy
      (with isthmectomy) and central node dissection is adequate if the tumor is
      located only in one lobe.

PMID- 18035965
TI  - Recent advances, trends and economic considerations in the risk assessment,
      prevention and treatment of postoperative nausea and vomiting.
AB  - During the last two decades there have been considerable achievements regarding
      the management of postoperative nausea and vomiting (PONV). Due to the importance
      of these symptoms in the aim to streamline clinical processes and to improve
      patient satisfaction, the debate on the best strategies and also research that
      focuses on PONV continues. This review summarises the recent developments with
      respect to the management of PONV. Following a brief review on what is already
      known on the risk assessment, prevention and treatment of PONV, newer trends in
      the pharmacological prevention (dexamethasone, neurokinin-1 antagonists,
      multimodal prevention) will be discussed as well as new insights regarding the
      value of algorithms for the prevention of PONV. Further, pharmacogenetically
      based algorithms (according to the metaboliser status) as well as new treatment
      strategies (dexamethasone, multimodal treatment) will be covered. No drug so far
      can achieve a reduction of PONV of more than one third. Furthermore, all clinical
      studies consistently demonstrated that a combination treatment has a simple
      additive effect without any relevant interaction between different drugs or
      classes of drugs. The relative reduction of approximately 30% can also be
      expected from dexamethasone and it is likely that the substances presently in
      development and in an early clinical use (e.g., neurokinin-1 antagonists) will
      not represent the new panacea. However, they will probably replenish the existing
      antiemetic portfolio to better cope with high risk patients. Stratified
      prevention using pharmacogenetic knowledge is still in the early stages.
      Algorithms need to be customized to the local settings in order to prove
      efficient. Treatment remains a most important pillar and there is evidence that
      the principles of combining antiemetics to prolong effects and improve protection
      can be similarly applied to treatment. Recent developments in the area of PONV
      are more related to implementing the already existing evidence than based on the
      introduction of new molecules. New molecules replenish the pharmacological
      antiemetic portfolio, which is needed due to the limited efficacy of any single
      agent available so far. The new neurokinin-1 receptor antagonist, aprepitant, and
      the long lasting 5-HT(3) receptor antagonist palonosetron are the latest
      developments in this context. Treatment is most important and can also be
      regarded as a secondary prevention. Due to limited efficacy of single treatment
      interventions, combination therapy may gain more widespread use in the future.

PMID- 18035966
TI  - Glaucoma: a review of adjunctive therapy and new management strategies.
AB  - Glaucoma is a major cause of vision loss throughout the world. Treatment for
      glaucoma consists of reducing intraocular pressure (IOP) to an acceptable target
      range to prevent further optic nerve damage. Typically, this involves the
      selection of a topical IOP-lowering agent. Five major classes of glaucoma
      medications are presently available for clinical use. These include alpha
      adrenergic agonists, beta-adrenergic antagonists (beta-blockers), carbonic
      anhydrase inhibitors (CAIs), cholinergics and prostaglandin analogs (PGAs).
      Although beta-blockers enjoyed great success as first-line glaucoma therapy for
      many years, recently the PGAs have gained favor as the initial treatment of
      choice for most patients. Although the PGAs offer robust IOP reduction as
      monotherapy, a significant number of patients will require an adjunctive agent
      for adequate IOP control. Recent studies have demonstrated that alpha-agonists,
      beta-blockers and CAIs can be used safely and effectively as adjunctive therapy
      for patients being treated with a PGA. Comparison studies are beginning to appear
      in the literature to help determine which adjunctive agent is the most effective
      when used in combination with a PGA. Additional IOP-lowering efficacy with
      adjunctive therapy does have limitations, particularly with the addition of a
      third or fourth agent. For those patients on maximal tolerated medical therapy
      who still need additional IOP reduction, other available options include laser
      trabeculoplasty and filtration surgery.

PMID- 18035967
TI  - Gemcitabine in bladder cancer.
AB  - Gemcitabine, a deoxycytidine analogue, is an inhibitor of DNA synthesis. With
      myelosupression being its most serious toxicity, gemcitabine has, however, a
      favourable toxicity profile. It was tested in urothelial bladder cancer at
      different stages of the disease. In superficial Bacillus Calmette-GuErin (BCG)
      resistant bladder cancer as well as in BCG-intolerant patients, intravesical
      gemcitabine instillation has demonstrated a significant activity. In the adjuvant
      setting, the combination of gemcitabine and cisplatin (GC) has proved to be a
      feasible protocol. In locally advanced and metastatic disease, GC is admitted as
      a standard alternative first-line regimen. Gemcitabine is also an interesting
      choice for unfit patients when used as a single treatment or in combination with
      other chemotherapeutic agents as carboplatin or taxanes. This article reviews
      most of the studies performed in order to promote the usefulness of gemcitabine
      in bladder cancer.

PMID- 18035968
TI  - Dasatinib for the treatment of Philadelphia chromosome-positive chronic
      myelogenous leukaemia after imatinib failure.
AB  - Dasatinib, a potent, oral kinase inhibitor, is presently approved for
      Philadelphia-positive chronic myelogenous leukaemia (CML) following imatinib
      failure. In an in vitro study, dasatinib had 325-fold greater potency than
      imatinib for inhibiting unmutated BCR-ABL. Phase I and II data show that
      dasatinib 70 mg b.i.d. is effective after imatinib failure in various phases of
      CML. Comparative data of dasatinib versus high-dose imatinib in patients with
      resistance or intolerance to imatinib demonstrated that dasatinib was associated
      with improved response rates and progression-free survival. Side effects of
      dasatinib, including pleural effusions, are manageable with modification of dose
      or schedule. Phase III dose optimisation studies and future indications are also
      discussed.

PMID- 18035969
TI  - Gemcitabine and carboplatin in combination for the treatment of advanced,
      metastatic, non-small cell lung cancer.
AB  - The universally accepted first-line treatment for advanced (stage IIIB
      effusion/IV) non-small-cell lung cancer in patients with a good performance
      status is a platinum drug in combination with one of gemcitabine, paclitaxel,
      vinorelbine or docetaxel. Although cisplatin is generally the favoured platinum
      agent, gemcitabine partnered with carboplatin is convenient to administer and has
      a favourable toxicity profile. Here, the pharmacology, preclinical and clinical
      data to support the use of this regimen for the treatment of advanced non-small
      cell lung cancer is evaluated.

PMID- 18035970
TI  - SRP-27 is a novel component of the supramolecular signalling complex involved in
      skeletal muscle excitation-contraction coupling.
AB  - SRP-27 (sarcoplasmic reticulum protein of 27 kDa) is a newly identified integral
      membrane protein constituent of the skeletal muscle SR (sarcoplasmic reticulum).
      We identified its primary structure from cDNA clones isolated from a mouse
      skeletal muscle cDNA library. ESTs (expressed sequence tags) of SRP-27 were found
      mainly in cDNA libraries from excitable tissues of mouse. Western blot analysis
      confirmed the expression of SRP-27 in skeletal muscle and, to a lower extent, in
      heart and brain. Mild trypsin proteolysis combined with primary-structure
      prediction analysis suggested that SRP-27 has four transmembrane-spanning alpha
      helices and its C-terminal domain faces the cytoplasmic side of the
      endo(sarco)plasmic reticulum. The expression of SRP-27 is higher in fast twitch
      skeletal muscles compared to slow twitch muscles and peaks during the first month
      of post-natal development. High-resolution immunohistochemistry and Western blot
      analysis of subcellular fractions indicated that SRP-27 is distributed in both
      longitudinal tubules and terminal cisternae of the SR, as well as in the
      perinuclear membrane systems and the nuclear envelope of myotubes and adult
      fibres. SRP-27 co-sediments with the RyR (ryanodine receptor) macromolecular
      complex in high-salt sucrose-gradient centrifugation, and is pulled-down by anti
      RyR as well as by maurocalcin, a well characterized RyR modulator. Our results
      indicate that SRP-27 is part of a SR supramolecular complex, suggesting the
      involvement of SRP-27 in the structural organization or function of the molecular
      machinery underlying excitation-contraction coupling.

PMID- 18035971
TI  - Risk factors for the introduction of avian influenza virus into commercial layer
      chicken farms during the outbreaks caused by a low-pathogenic H5N2 virus in Japan
      in 2005.
AB  - Avian influenza outbreaks caused by a low-pathogenic H5N2 virus occurred in Japan
      from June to December 2005. All 41 affected farms housed layer chickens.
      Therefore, we conducted a case-control study targeting all commercial layer
      chicken farms within the movement restriction areas in Ibaraki prefecture, where
      most outbreaks were detected, to investigate the risk factors for the
      introduction of avian influenza virus (AIV). Four variables were identified as
      risk factors associated with the introduction of AIV by multivariate logistic
      regression: 'introduction of end-of-lay chickens ' (odds ratio (OR) = 36.6),
      'sharing of farm equipment among farms' (OR = 29.4), 'incomplete hygiene measures
      of farm visitors on shoes, clothes and hands' (OR = 7.0), and 'direct distance to
      the nearest case farm' (0-500 m, OR = 8.6; 500-1000 m, OR = 0.8; 1000-1500 m, OR
      = 20.1; referenced more than 1500 m). We fully believe that strict biosecurity
      measures should be applied against any incursion points so as not to introduce
      AIV into more farms.

PMID- 18035972
TI  - Antimicrobial resistance in bacteria from Swiss veal calves at slaughter.
AB  - Bacteria with antimicrobial resistance can be transferred from animals to humans
      and may compromise antimicrobial treatment in case of infection. To determine the
      antimicrobial resistance situation in bacteria from Swiss veal calves, faecal
      samples from 500 randomly selected calves originating from 129 farms were
      collected at four big slaughterhouses. Samples were cultured for Escherichia
      coli, Enterococcus sp. and Campylobacter sp. and isolated strains were tested for
      antimicrobial susceptibility to selected antimicrobial agents by the minimal
      inhibitory concentration technique using the broth microdilution method. From 100
      farms, data on farm management, animal husbandry and antimicrobial treatments of
      the calves were collected by questionnaire. Risk factors associated with
      antimicrobial resistance were identified by logistic regression. In total, 467 E.
      coli, 413 Enterococcus sp. and 202 Campylobacter sp. were isolated. Of those,
      68.7%, 98.7% and 67.8%, respectively, were resistant to at least one of the
      tested antimicrobial agents. Resistance was mainly observed to antimicrobials
      frequently used in farm animals. Prevalence of resistance to antimicrobials
      important for human treatment was generally low. However, a rather high number of
      quinupristin/dalfopristin-resistant Enterococcus faecium and ciprofloxacin
      resistant Campylobacter sp. were detected. External calf purchase, large
      finishing groups, feeding of milk by-products and administration of
      antimicrobials through feed upon arrival of the animals on the farm significantly
      increased the risk of antimicrobial resistance at farm level. Participation in a
      quality assurance programme and injection of a macrolide upon arrival of the
      animals on the farm had a protective effect. The present study showed that veal
      calves may serve as a reservoir for resistant bacteria. To ensure food safety,
      veal calves should be included in the national monitoring programme for
      antimicrobial resistance in farm animals. By improving farm management and calf
      husbandry the prevalence of resistance may be reduced.

PMID- 18035973
TI  - Mastitis caused by Yersinia pseudotuberculosis in Israeli dairy cattle and public
      health implications.
AB  - Yersinia pseudotuberculosis was isolated from mastitis cases in nine dairy cows
      in Israel. Six cases occurred on one farm (three instances of two cows, 2 months
      apart) and three cases on one farm each. Seven cows suffered from clinical and
      two from subclinical mastitis. All but two of the cows were culled. The
      literature describing cases of bovine mastitis caused by Y. pseudotuberculosis is
      reviewed and the human public health implications are discussed.

PMID- 18035974
TI  - Surveillance of dairy production holdings supplying raw milk to the farmhouse
      cheese sector for Escherichia coli O157, O26 and O111.
AB  - Clinically healthy domestic animals can harbour Escherichia coli O157 and other
      verocytotoxigenic E. coli (VTEC) strains in their faeces. Milk filters can be
      used to microbiologically monitor direct milk secretion and environmental
      contamination for these pathogens. The aim of this study was to establish
      baseline data on the prevalence and characteristics of VTEC organisms in
      lactating animals (bovine, ovine and caprine) supplying milk to the farmhouse
      cheese sector, with particular emphasis on serogroups O157, O111 and O26. Fifty
      six bovine, 13 caprine and 5 ovine herds/flocks, the majority of which supplying
      milk for farmhouse cheese production, were surveyed from May 2004 to July 2005.
      Milk filters were analysed by immunomagnetic separation followed by PCR, on a
      serogroup-specific basis for E. coli O157, O26 and O111. Positive isolates were
      examined using a multiplex PCR protocol, for their potential to produce
      verocytotoxins (vt1/vt2), the haemolysin-encoding gene (hlyA) and the gene
      encoding attaching and effacement (eae). Five verocytotoxigenic and 22 non
      virulent E. coli O157 isolates were detected. Seventeen E. coli O26 isolates were
      also detected, four of which were verocytotoxigenic, seven isolates contained the
      eae gene only and six isolates were devoid of any of the virulence factors. The
      VTEC O157 and O26 isolates contained the hlyA and eae genes along with the
      verocytotoxin genes. No E. coli O111 isolates were detected. Some of the herds
      were positive on more than one occasion and multiple E. coli serogroups were
      isolated from the same milk filter sample. Although all food products tested were
      VTEC negative, routine surveillance for such pathogens in raw milk/raw milk
      products is of public health importance. Herd-level surveillance along with
      subsequent risk management action may be a cost-effective component of risk
      reduction strategies for food production, drinking water supplies and the
      protection of public health.

PMID- 18035975
TI  - Importance of prudent antibiotic use on dairy farms in South Carolina: a pilot
      project on farmers' knowledge, attitudes and practices.
AB  - Inappropriate use of antibiotics in humans and animals contributes to decreased
      antimicrobial susceptibility in bacteria of medical importance. Resistant
      bacteria being transferred from animals to humans are causing public health
      concern. In-person interviews were conducted with 20 dairy farmers in rural
      counties of South Carolina to determine farmers' knowledge and attitudes about
      prudent antibiotic use among livestock. Four focus groups (n = 22) were also
      conducted to ascertain farmers' specific information needs about proper
      antibiotic use. Survey results showed that participants (100%) typically
      determined a need for antibiotic treatment using symptom assessment and reported
      following some form of operating procedures regarding administration of
      antibiotics. Few farmers (32%) had actual written antibiotic protocols. Preferred
      information sources about antibiotics were veterinarians (100%) and other dairy
      farmers (50%). Most farmers (86%) were not concerned that overuse of antibiotics
      in animals could result in antibiotic resistance among farm workers. Qualitative
      analysis of focus groups revealed significant barriers to following proper
      antibiotic procedures including limited finances and lack of time. The need for
      bilingual educational resources for Hispanic/Latino dairy workers was expressed.
      Desired formats for educational materials were posters, flowcharts, videos, and
      seminars. Education of South Carolina dairy farmers by veterinarians and public
      health professionals on the appropriate use of antibiotics in dairy cattle is
      needed to ensure antibiotic effectiveness in both animals and humans.

PMID- 18035976
TI  - Non-structural protein 3A for differentiation of foot-and-mouth disease infected
      and vaccinated animals in Haryana (India).
AB  - There are severe international trade restrictions on foot-and-mouth disease (FMD)
      affected areas. Because of endemic nature of FMD, India started FMD control
      programme (FMD-CP) using mass vaccination in selected states including Haryana
      (year 2003). Although no significant incidence of the disease was reported after
      launching FMD-CP in the state but in order to participate in international trade
      of animal and animal products, veterinary authorities have to prove that there is
      no FMD virus (FMDV) circulation in the animal population, for which it is
      necessary to differentiate the FMD infected and vaccinated animals. For this
      purpose, an in-house indirect ELISA utilizing baculovirus-expressed FMDV non
      structural protein (NSP) 3A was used to find evidence for virus circulation
      (prevalence of anti-NSP 3A-specific antibodies) by examining serum samples that
      were collected either before start of FMD-CP or after completion of third phase
      (Pre-4th) of vaccination in Haryana (India). A significant reduction (P < 0.01)
      in prevalence of anti-NSP 3A-specific antibodies (possibly carriers) was observed
      2 years after launching FMD-CP in Haryana. However, in cattle the percentage of
      animals with anti-NSP 3A-specific antibodies was found to be significantly higher
      (P < 0.01) than buffalo, both before (P < 0.01) and after (P < 0.01) launching
      FMD-CP in the state. The findings of this study suggest that use of FMDV vaccine
      in cattle and buffaloes in endemic areas reduces virus circulation (carriers) in
      the vaccinated herds and that the current 3ANSP-ELISA can be successfully used to
      monitor the FMDV circulation in endemic areas.

PMID- 18035977
TI  - Action of disinfectants on canine coronavirus replication in vitro.
AB  - Canine coronavirus (CCoV) is responsible for enteric disease in pups. Infected
      dogs generally have a rapid recovery, so the virus is highly contagious and the
      spread of infection is difficult to control. Chemical disinfectants have been
      widely used in human disease-control programmes to prevent viral infectious
      diseases from spreading, but to date, there are no studies in the literature on
      the sensitivity of CCoV to chemical biocides. The present study investigated the
      sensitivity of CCoV to disinfectants currently used for prophylaxis in kennel and
      dog breeding locations. The effects of three agents: alkyl-dimethyl-benzyl
      ammonium chloride, benzalkonium chloride and didecyl-dimethyl-ammonium chloride,
      on the infectivity titre of CCoV in A72 cell lines, were studied at different
      concentrations. Although they may regard a small number of agents, the findings
      showed that the sensitivity of CCoV to disinfectants varies and the differences
      are dose correlated. In general, virus inactivation implies a permanent loss of
      infectivity which can be evaluated in suspensions and hand disinfection tests.

PMID- 18035978
TI  - Anti-neosporal IgG and IgE antibodies in canine neosporosis.
AB  - Neospora caninum infection provokes neurological disorders, recurrent abortion
      and death in dogs and cattle. Dogs are both intermediate and definitive host of
      N. caninum. Thus, the development of sensitive and specific immunoassays to
      diagnose canine neosporosis is essential to control this disease. This work
      investigated serum anti-neosporal IgG and IgE antibodies in 140 dogs represented
      by 30 healthy animals (group I), 11 dogs showing acute N. caninum infection
      (group II), 50 urban dogs with serological evidence of canine neosporosis in
      indirect fluorescent antibody test (IFAT) (group III) and 49 urban dogs without
      clinical and laboratory evidences of neosporosis (group IV). Enzyme-linked
      immunosorbent assay (ELISA) and western immunoblotting, both using a soluble N.
      caninum tachyzoite antigen (SNA), investigated these two isotypes of antibodies,
      while a Urea-ELISA measured the avidity of the IgG antibodies. Anti-Toxoplasma
      gondii IgG antibodies were also investigated in the animals. Anti-neosporal IgG
      was found in all animals from groups II and III, whereas 32.7% (16/49) of dogs
      from group IV were reactive. IgG antibodies of low avidity were demonstrated in
      dogs from group II (median 35.3%), while animals from groups III and IV had IgG
      antibodies of high avidity (medians of 61.5% and 61.7% respectively). IgE
      antibodies were found in four (13.3%) and five (16.6%) dogs from groups III and
      IV respectively. Dogs presenting acute infection (group II) or chronic infection
      (group III) had IgG antibodies to several neosporal antigens, mainly of 29-30 and
      35 kDa, while 13 of 16 dogs from group IV recognized antigens from 14 to 170 kDa.
      Antibodies to T. gondii were detected in 36 of 50 (72%) sera from group III and
      25 of 49 (51%) sera from group IV. We concluded that IgG-ELISA and Urea-ELISA
      with SNA may substitute for IFAT in both laboratory routine and epidemiological
      studies of canine neosporosis.

PMID- 18035979
TI  - Prevalence and phylogenetic analysis of Cryptosporidium in pigs in eastern China.
AB  - Faecal samples from 1488 pigs were collected from six pig farms in Jiangsu
      province and Shanghai city, eastern China, stained by the modified acid-fast
      staining technique (MAFS) and observed by light and phase contrast microscopy to
      identify Cryptosporidium oocysts. A total of 178 (12%) positive animals were
      detected. Three randomly selected MAFS-positive samples from each farm were
      further analysed by reverse-transcription polymerase chain reaction (RT-PCR)
      using primers designed to amplify DNA fragments from the small subunit ribosomal
      RNA (SSU rRNA) gene. PCR products from two positive samples were sequenced.
      Phylogenetic analysis and a distances matrix generated from these sequences
      showed that the isolates belonged to the species C. parvum, and were most similar
      to the C. parvum'mouse' genotype. The identification of this C. parvum genotype
      in pigs has not been reported previously. These findings are discussed in the
      context of the epidemiology of Cryptosporidium on pig farms.

PMID- 18035980
TI  - Acanthosis nigricans: a common finding in overweight youth.
AB  - We evaluated the prevalence of acanthosis nigricans among urban youth. Youth (7
      17 years) at nine pediatric practices completed surveys on demographics and
      family history of diabetes and had weight and height measured. Acanthosis
      nigricans was scored and digital photography of the neck performed. A total of
      618 youth were included in the analysis: mean age 11.5 years; 51% female; 61%
      African American, 27% Hispanic, 12% Caucasian, and 32% with body mass index
      >or=95th percentile. Acanthosis was found in 19%, 23%, and 4% of the African
      American, Hispanic, and Caucasian youth, respectively, and in 62% of youth with a
      body mass index >or=98 th percentile. Using multiple logistic regression, we
      found increasing body mass index z-score, presence of maternal gestational
      diabetes, female gender, and not being Caucasian each were independently
      associated with acanthosis nigricans. Acanthosis was common among overweight
      youth and was associated with risk factors for glucose homeostasis abnormalities.
      Acanthosis nigricans can be a trigger to counsel families on its causes and
      consequences; and thus motivate them to make healthy lifestyle changes that can
      decrease the risk of developing cardiovascular disease or diabetes.

PMID- 18035981
TI  - Immunologic changes in TNF-alpha, sE-selectin, sP-selectin, sICAM-1, and IL-8 in
      pediatric patients treated for psoriasis with the Goeckerman regimen.
AB  - Psoriasis is a chronic inflammatory skin disease which is often manifested during
      childhood. The present study investigated changes in the serum levels of
      proinflammatory cytokines and soluble forms of adhesion molecules in children
      with psoriasis. The observed patient group of 26 children was treated with the
      Goeckerman regimen. This therapy combines dermal application of crude coal tar
      with ultraviolet radiation. The Psoriasis Area Severity Index decreased
      significantly after treatment by with the Goeckerman regimen (p < 0.001). Serum
      levels of the proinflammatory cytokine TNF-alpha and adhesion molecules sICAM-1,
      sP-selectin and sE-selectin decreased after the Goeckerman regimen. The TNF-alpha
      and sICAM-1 decreased significantly (p < 0.05). Our findings support the complex
      role of these immune parameters in the immunopathogenesis of psoriasis in
      children. The serum level of IL-8 increased after the Goeckerman regimen. This
      fact indicates that the chemokine pathway of IL-8 activity could be modulated by
      this treatment, most likely by polycyclic aromatic hydrocarbons.

PMID- 18035982
TI  - Oral cyclosporin plus topical corticosteroid therapy diminishes bone mass in
      children with eczema.
AB  - Topical corticosteroids remain the most common treatment for eczema; however, it
      is uncertain whether long-term use of these agents has any adverse effect on bone
      mass. Cyclosporin is very useful in patients with severe atopic dermatitis who
      have failed conventional therapy. It has been shown to induce bone loss. We
      compared 43 children with severe eczema who were using topical corticosteroids
      with 73 healthy children. Of the 43 patients, six were also taking cyclosporin.
      Bone mineral density was measured in the lumbar spine and in the femoral neck
      using dual-energy X-ray absorptiometry. In multivariate analysis, subjects with
      eczema had lower lumbar spine bone mineral density (-0.03 g/cm(2); p = 0.015) and
      bone mineral apparent density (-0.01 g/cm(3); p = 0.008) but higher FN BMAD
      (+0.02 g/cm(3); p = 0.029) compared with controls. Patients with eczema on
      topical corticosteroids who had used cyclosporin had lower lumbar spine bone
      mineral apparent density (-0.01; p = 0.006) compared with those only on topical
      corticosteroids in both adjusted and unadjusted analysis. In conclusion, children
      with severe eczema have decreased lumbar spine bone mass, which is primarily
      mediated by cyclosporin use rather than by topical corticosteroid use. This
      effect is likely to lead to a modest increase in the risk of wrist and forearm
      fractures in children using this agent.

PMID- 18035983
TI  - "Pediatric blaschkitis": expanding the spectrum of childhood acquired Blaschko
      linear dermatoses.
AB  - We describe two young children who developed relapsing, pruritic, papulovesicular
      eruptions in multiple bands along Blaschko lines on the neck, trunk, and
      extremities. Skin specimens in both revealed spongiotic dermatitis. This
      represents the first report of "blaschkitis" in children, providing further
      evidence that lichen striatus and blaschkitis are related acquired Blaschko
      linear dermatoses that exist on a spectrum rather than as the childhood and adult
      form of a single disease entity. We highlight the features that differentiate
      blaschkitis from lichen striatus, review the potential roles of cutaneous
      mosaicism, environmental triggers, and background immunologic state in their
      pathogenesis, and discuss the spectrum of inflammatory dermatoses that can follow
      Blaschko lines.

PMID- 18035984
TI  - Myokymia as a presenting sign of congenital smooth muscle hamartoma.
AB  - We report a 4-week-old male infant with intermittent asymptomatic bouts of
      vermicular movements of the skin (myokymia). Myokymia started at the age of 4
      days. Attacks occurred approximately every 30-60 minutes and could be elicited by
      gently stroking the skin. Macroscopically no abnormalities typical for smooth
      muscle hamartoma such as hypertrichosis or hyperpigmentation were observed.
      Histologic examination of a skin biopsy specimen showed bundles of hyperplastic
      smooth muscle tissue within the reticular dermis which were associated with hair
      follicles. Karyotyping did not reveal any structural or numeric chromosomal
      anomaly. The findings led to the diagnosis of congenital smooth muscle hamartoma.
      On follow-up at the age of 24 months myokymia persisted, but with a marked
      reduction in the number of attacks per day. The phenomenon of myokymia results
      from neurally induced spontaneous contraction of dermal smooth muscles. It is
      also known as "pseudo-Darier's sign." While most of those affected previously
      reported had hypertrichosis or hyperpigmentation, this patient seems to be the
      first to present with myokymia alone.

PMID- 18035985
TI  - Medallion-like dermal dendrocyte hamartoma.
AB  - Medallion-like dermal dendrocyte hamartomas are rare congenital cutaneous
      lesions, with only three occurrences reported in the English language literature.
      They present at birth as asymptomatic circular, oval, or triangular well
      circumscribed, atrophic patches. Typically, they have an erythematous or yellow
      brown hue and a characteristic pliable, wrinkled surface; subtle telangiectases
      may also be appreciated. They may be misdiagnosed as atrophoderma, cutis aplasia,
      or anetoderma. All reported patients have been female. Characteristic histologic
      findings include epidermal atrophy and the presence of a CD34-positive spindle
      cell proliferation in the dermis. This spindle cell proliferation represents a
      population of dermal dendrocytes, which are bone marrow-derived cells that are
      believed to function as antigen-presenting cells that contribute to the function
      of the skin immune system. Little is known about the pathophysiology of medallion
      like dermal dendrocyte hamartomas. We present a patient with this entity and
      review similar presentations reported in the literature.

PMID- 18035986
TI  - Eruptive lichen planus in a child.
AB  - Lichen planus is a chronic inflammatory disease of the skin and mucous membranes.
      Typically, skin lesions include violaceous, polygonal, flat papules and plaques.
      However, the clinical presentation of lichen planus can be heterogeneous and show
      divergent degrees of cutaneous and mucous manifestation. The disease usually
      affects adults and is only rarely encountered in children. Here, we present a 7
      year-old boy who rapidly developed itching skin lesions on the extremities and
      trunk. He had no history of concomitant drug intake, infection or vaccination.
      Clinical examination of the skin found multiple white-grayish papules and plaques
      whereas the scalp, mucous membranes and nails were not affected. Histologic
      examination showed typical findings of lichen planus. We initiated topical
      corticosteroid therapy, which resulted in healing of the skin lesions within 4
      weeks. To our knowledge this is the first instance of exanthematous lichen planus
      in childhood successfully treated with topical corticosteroid ointment alone.
      Thus, even generalized lichen planus lesions can be effectively cleared without
      systemic therapies, which can be potentially associated with serious side
      effects, especially in children.

PMID- 18035987
TI  - Granulomatous slack skin disease in a child: the outcome.
AB  - Granulomatous slack skin syndrome is a rare clinical and pathologic disorder.
      Only 42 patients have been reported, one of whom we described in 1997--the only
      child so far reported. We now describe the evolution of this patient and the
      transformation of the disease into a peripheral T-cell lymphoma, and the
      complications resulting in the child's death.

PMID- 18035988
TI  - Nasal dermoid sinus cyst.
AB  - Midline congenital abnormalities of the skin may be related to subjacent visceral
      developmental defects. We report on three unrelated children presenting a small
      midline pit on the bridge of the nose from which a small tuft of hair was
      emerging. This presentation is the hallmark of a nasal dermoid sinus cyst. In one
      of the patients the sinus tract was connected to the anterior cerebral fossa and
      required neurosurgical management. Although midline cutaneous abnormalities may
      look trivial, dermatologists should keep a high index of suspicion for possible
      association with more severe underlying defect. The diagnosis of nasal dermoid
      sinus cyst requires appropriate imaging studies to determine the extension of the
      sinus tract thus allowing proper management.

PMID- 18035989
TI  - Adams-Oliver syndrome with widespread CMTC and fatal pulmonary vascular disease.
AB  - We report a neonate with cutis marmorata telangiectatica congenita and clinical
      features of Adams-Oliver syndrome in association with severe pulmonary vascular
      disease. We provide an overview of cutis marmorata telangiectatica congenita,
      distinguishing it from cutis marmorata, a common and benign physiologic cutaneous
      disorder seen in neonates. We highlight the need for thorough medical evaluation
      in cutis marmorata telangiectatica congenita to exclude associated congenital
      anomalies.

PMID- 18035990
TI  - Lymphangioma scroti.
AB  - Lymphangiomas are congenital malformations of the lymphatic system. We report a
      10-year-old boy with lymphatic malformation of the scrotum, which presented as a
      multiloculated scrotal mass associated with edema of the left thigh and left
      cryptorchidism. Histopathologic examination showed scrotal lymphangioma
      cavernosum. Ultrasonography was of major importance for the preoperative
      diagnosis and to determine the extent of the scrotal lesion. Scrotal
      lymphangiomas are very rare. It is important to consider them in boys with a
      cystic scrotal mass in order to avoid misdiagnosis, improper treatment and
      recurrences.

PMID- 18035991
TI  - Multiple accessory tragi and hemifacial microsomia.

PMID- 18035992
TI  - Ulcerative infiltrated plaques in a Bolivian boy.

PMID- 18035993
TI  - Abnormal scalp hair pattern in an infant.

PMID- 18035994
TI  - Pancreatic panniculitis in a 4-year-old child with nephrotic syndrome.
AB  - Pancreatic panniculitis is an uncommon disorder with a distinctive
      histopathology. We report the youngest patient with pancreatic panniculitis
      caused by hypertriglyceridemia in association with nephrotic syndrome.

PMID- 18035995
TI  - A mild form of Proteus syndrome.
AB  - Proteus syndrome is a multisystem disorder and diagnosis has been difficult
      because of the variability of the syndrome's manifestations. Dermatologists have
      an important role as cutaneous findings could provide clues for the early
      diagnosis of the disease. Herein we report a case who had cerebriform connective
      tissue nevus and lipoma as the sole manifestations of the disease.

PMID- 18035996
TI  - Neonatal Kawasaki disease with multiple coronary aneurysms and thrombocytopenia.
AB  - We describe an occurrence of Kawasaki disease presenting in the neonatal period
      with multiple coronary aneurysms. Very few such presentations of this entity have
      been described in the literature and this is probably the youngest patient
      reported from India. We also highlight an atypical finding, thrombocytopenia
      during the second week of life and beyond.

PMID- 18035997
TI  - Riga-Fede disease associated with postanoxic encephalopathy and trisomy 21: a
      proposed classification.
AB  - We present a new instance of Riga-Fede disease in a 2-year-old boy with Down
      syndrome and postanoxic encephalopathy. We propose a classification of the
      disease, as either "precocious," associated with natal or neonatal teeth or "late
      onset," associated with neurologic disease.

PMID- 18035998
TI  - A recurrent drug rash with eosinophilia and systemic symptoms.

PMID- 18035999
TI  - Vitiligo in children.

PMID- 18036000
TI  - Acrodermatitis enteropathica with depigmented skin lesions simulating vitiligo.

PMID- 18036001
TI  - Juvenile xanthogranuloma en plaque.

PMID- 18036003
TI  - Cultural diversity in health care.

PMID- 18036004
TI  - Adolescents' experiences of well-being when living with a long-term illness or
      disability.
AB  - Present-day society has produced changes in family living patterns and conditions
      and this has resulted in new stressors and health problems. Most children and
      adolescents with chronic diseases and disabilities, who were previously cared for
      at hospitals and institutions for long periods, are now integrated in society and
      they are expected to live a normal life in the conditions that currently prevail.
      The number of young people with long-term illnesses/disability has increased
      worldwide during the last decades. There is lack of studies relating to the way
      young people regard their daily lives and factors that are important for their
      well-being. The aim of this study was to describe the meaning of feeling good in
      daily life in adolescents living with a long-term illness or disability. Eight
      boys and seven girls, aged between 12 and 19 years, with different conditions of
      long-term illness or disability, participated in the study. Tape-recorded
      interviews were conducted between the years 2003-2004 and the data were analysed
      using content analysis. The results revealed that the adolescents with long-term
      illness generally experienced well-being like everybody else. Three themes were
      found to be important in order to feel good: 'a feeling of acceptance of
      illness/disability as a natural part of life', 'a feeling of support' and 'a
      feeling of personal growth'. This study concludes that adolescents with long-term
      illness or disabilities experience well-being when they are allowed to prepare
      for living a normal life integrated in society.

PMID- 18036005
TI  - Nurses in paediatric care--self-reported professional self and perceived research
      utilization.
AB  - The aim was to describe how nurses in different professional levels evaluated
      their professional self and perceived barriers to research utilization in
      paediatric care. The sample consisted of three groups of nurses: control, trainee
      and specialists (n = 113) employed at two Paediatric University hospitals in
      Sweden. The control and trainee groups were nurses with a general education and
      the specialists had a specialist education in paediatric care. The nurses
      answered the two questionnaires: the Professional Self Description Form (PSDF)
      and the Barriers Scale. The results showed that the highest scores in the PSDF
      were found in sensitivity in all the three groups and consideration (in control
      and specialist group) and creativity (trainee group). The control group scored
      significantly higher in the item persistence. In the Barriers Scale, the three
      groups scored the greatest barriers in; 'there is insufficient time on the job to
      implement new ideas' and 'the nurses do not have time to read research'. The
      lowest barriers were found in; 'the nurse is unwilling to change/try new ideas'
      and 'the nurse is unaware of research'. The specialist nurses had significantly
      higher barriers in; 'the nurse is isolated from knowledgeable colleagues with
      whom to discuss the research', 'the nurse is unwilling to try new ideas' and
      'administration will not allow implementation'. No correlations were found
      between the PSDF and the Barriers Scale. In conclusion, the self-evaluation of
      professional self and perceived research utilization showed few differences
      between the nurses. These findings indicate that the professional self is
      independent of educational level and work experiences while barriers to research
      utililization increases with competence and experience.

PMID- 18036006
TI  - Functioning in everyday life after stroke: a longitudinal study of elderly people
      receiving rehabilitation at home.
AB  - OBJECTIVE: There is a need to identify different rehabilitation needs over time
      among individuals with stroke in order to implement client-centred rehabilitation
      interventions after stroke. The objective of this research was to describe
      changes in some aspects of functioning and to explore the patterns of change in
      functioning in everyday life during the first year after stroke for elderly
      patients participating in rehabilitation at home. DESIGN AND SUBJECTS: Patients
      who fulfilled the inclusion criteria for a regular rehabilitation-at-home
      programme after stroke were considered for participation in this study. Twenty
      seven elderly patients participated on four data collection occasions during the
      year immediately subsequent to a stroke. The mean age of the 27 participants was
      78.8 years (SD = 5.9) and 67% of the participants were women. METHODS: Data on
      certain aspects of functioning were collected and a person-oriented approach was
      used to describe the patterns in the change in functioning for individuals.
      RESULTS: Four different patterns were identified: (a) moderate change in
      functioning (n = 4), (b) minor change in functioning (n = 11), (c) minor change
      despite major life event (n = 7), (d) disrupted change in functioning (n = 5).
      The study group improved significantly in most aspects of functioning, but still,
      most participants (n = 20) showed dissatisfaction with life as a whole 12 months
      after their stroke. CONCLUSION: This study identified different patterns of
      change in functioning in everyday life. This knowledge should serve to help guide
      rehabilitation professionals in their assessment of clients' needs during
      different phases after stroke.

PMID- 18036007
TI  - Perceived health six months after delivery in women who have experienced low back
      pain and pelvic pain during pregnancy.
AB  - BACKGROUND AND OBJECTIVES: A majority of women suffer from low back pain and
      pelvic pain (LBPP) during pregnancy. The aim of the study was to investigate
      perceived health, sexual life, social situation, sick leave and use of medical
      services 6 months after pregnancy in women with LBPP during pregnancy. RESEARCH
      METHODS: In a previous questionnaire study, 72% (n = 639) of the respondents had
      reported LBPP during pregnancy. These respondents were sent a second
      questionnaire approximately 6 months after delivery. The respondents were divided
      into three groups: 'no pain', 'recurrent pain' and 'continuous pain'. Pearson's
      chi-squared test was used to test the difference between groups. RESULTS:
      Perceived health status 6 months after pregnancy was less favourable for women
      with persistent LBPP compared to women with remission of LBPP. Family situation,
      change of relationship and sexual life did not differ among women with remission
      of LBPP or persistent LBPP after pregnancy. Four of 10 women with persistent LBPP
      had sought medical care, and two of 10 had been on sick leave because of LBPP
      after pregnancy. CONCLUSIONS: Perceived health status was less favourable for
      women with persistent LBPP after pregnancy. Use of medical services among women
      with persistent LBPP was prevalent.

PMID- 18036008
TI  - Self-care as a health resource of elders: an integrative review of the concept.
AB  - AIM: To review the literature related to self-care and health promotion for
      elders and to develop an understanding of self-care as a health resource.
      BACKGROUND: Self-care may improve health and prevent illness and disabilities in
      elders. Although studies of self-care are numerous, the significance of the
      concept as a health resource for elders lacks clarity. Before 1989, research
      focused principally on medical self-care at the expense of health care, and self
      care was seen more as supplementary to professional health care rather than as a
      health-promoting approach in health care. METHOD: In this integrative review from
      2006, we selected theoretical and empirical articles published between 1990 and
      2006, where self-care was related to elders' health promotion. Data were
      extracted from primary sources and included definitions of self-care, critical
      attributes, antecedents, goals and outcomes. We interactively compared data and
      display matrices to describe self-care as a health resource. RESULTS: Fifty-seven
      articles addressed health self-care and were integrated into a framework of self
      care as a health resource of elders. Self-care was identified as a two
      dimensional construct including action capabilities and processes for health in
      self-care practice. The capabilities consisted of fundamental capabilities, power
      capabilities and performance capabilities. The action processes included a
      process of life experience, a learning process and an ecological process.
      CONCLUSION: This review offers insight into self-care as a significant health
      resource of elders with different health status. It suggests that an elder's self
      care ability is determined by the interaction of various sub-resources and
      conditions and emphasizes the constantly evolving nature of self-care. The
      framework may be of use in clinical practice, policy-making and research into
      health care of frail or robust elders.

PMID- 18036009
TI  - Perceptions of how sleep is influenced by rest, activity and health in patients
      with coronary heart disease: a phenomenographical study.
AB  - OBJECTIVE: A framework is needed for identifying internal and external factors
      essential for the nursing management of psychological supportive health care and
      education for patients' self-care in sleep. In order to generate more knowledge
      from the patient's perspective, the aim of this study was to describe how
      patients with coronary artery disease (CAD) perceive that their sleep is
      influenced by rest, activity and health in outpatient care. DESIGN: Qualitative
      interviews were performed with 33 outpatients. METHOD: The data were analysed
      using a phenomenographic method. FINDINGS: Three descriptive categories of the
      phenomenon were described: my lifestyle is reflected in my sleep behaviour;
      handling the practices around tiredness and sleep; and feelings of negative and
      positive efficacy. Feelings of tiredness, fatigue and sleepiness were different
      pre-sleep stages, but were also related to the patient's adaptation and recovery.
      Creating one's own personal time and feelings of efficacy gave an inner sense of
      strength which is indicated as being particularly important in managing stress
      and the demands of everyday life in a satisfactory manner. CONCLUSION: From a
      contextual, holistic perspective on health, it is important to identify the
      patient's needs, symptoms and intentional or unintentional self-care management
      strategies regarding sleep and lifestyle. To promote a positive health outcome it
      is essential to identify sleeplessness behaviour and perceived self-efficacy for
      self-care in sleep.

PMID- 18036010
TI  - Adolescents with inflammatory bowel disease feel ambivalent towards their
      parents' concern for them.
AB  - This is a grounded theory study to identify concepts for describing how
      adolescents with inflammatory bowel disease (IBD) respond to their parents'
      concern for them. Ten adolescent boys and seven girls were interviewed. In the
      analysis four main categories emerged: ambivalence, ability/inability,
      compliance/resistance and trust/distrust. We found ambivalence to be the most
      distinctive theme to appear in the way in which these young people described how
      they felt about their parents' response to their disease. The core category
      ambivalence was expressed as an oscillation between seeking close contact with
      one's parents or, sometimes, staving them off, one moment feeling anxiously
      dependent upon them or turning to them for protection and support and the next,
      trying to achieve a dialogue with them. The core category comprised three
      subcategories, ability/inability, compliance/resistance and trust/distrust. The
      clinical support for young individuals with IBD should include an awareness of
      the simultaneous existence of conflicting attitudes, reactions and emotions.

PMID- 18036011
TI  - Aspects of spirituality concerning illness.
AB  - The spiritual dimension of illness, health and care may be seen as a unique
      aspect in addition to the physical, mental and social dimension. This
      contribution describes experiences of patients, nurses and hospital chaplains in
      relation to the spiritual aspects of being ill. Qualitative research was
      performed with the design of a focus group study, consisting of 13 focus groups
      with a total of 67 participants. A purposive sample was used comprising patients,
      nurses and hospital chaplains working in oncology, cardiology and neurology in
      different institutions and regions in the Netherlands. The qualitative analysis
      consisted of open coding and the determining of topics, followed by the
      subsequent attachment of substantial dimensions and characteristic fragments.
      Data were analysed by using the computer program KWALITAN. Spirituality play
      various roles in patients lives during their illness. There is a wide range of
      topics that may have an individual effect on patients. Despite differences in
      emphasis, the topics play a role in different patient categories. Although the
      spiritual topics seem to manifest themselves more clearly in long-term care
      relationships, they may also play a role during brief admittance periods (such as
      treatment decisions). The spiritual topics that arise from this study offer
      caregivers a framework for signalling the spiritual needs of patients. The
      question is not whether spirituality is a relevant focus area in care, but how
      and to what degree it plays a role with individual patients. Follow up research
      should aim at further exploration of spiritual aspects in care, the relationship
      between spirituality and health and at effective training of caregivers.

PMID- 18036012
TI  - Nurses perceptions of older patients integrity in long-term institutions.
AB  - AIM: This article reports on a study into nurses' perceptions of how the
      integrity of older patients is maintained in long-term care institutions in
      Finland. BACKGROUND: Patient integrity is an important aspect of ethical decision
      making in nursing care and respect for integrity is central to good care.
      Problems may occur in the maintenance of older patients' integrity because of
      reduced communication skills and decision-making authority. Data collection was
      by means of a purpose-designed structured questionnaire in a sample of 222 nurses
      from four purposively selected long-term institutions in 2004. The response rate
      was 74%. The questionnaire consisted of a background data sheet and integrity
      items in three categories: psychological, physical and social integrity. RESULTS:
      The nurses gave the highest ratings for the maintenance of physical integrity,
      particularly for respectful and gentle touching. Nonetheless, according to nurses
      patients were often tied to their bed or chair. The second highest ratings were
      give to the maintenance of social integrity. Most nurses felt that the patients
      had good contact with the outside world, mainly family members. On the other hand
      loneliness was a more common problem for older people in institutions. The
      maintenance of psychological integrity received the lowest rating. Satisfaction
      with the job and with the quality of service provided correlated positively with
      the nurses' views on the maintenance of patient integrity. CONCLUSION: Nurses
      take the view that patient integrity is maintained reasonably well in long-term
      institutions. There are, however, some problematic areas that require special
      attention, particularly in the maintenance of psychological integrity. Future
      research needs to look at how patients and their relatives view the situation and
      to explore different training delivery options that can help raise the ethical
      quality of nursing care.

PMID- 18036013
TI  - Patients' and nurses' experiences of the caring relationship in hospital: an
      aware striving for trust.
AB  - The phenomenon, caring relationship, has been widely studied in earlier research.
      Nevertheless, empirical studies in hospital, concerning patients and nurses
      experiences of the actual phenomenon caring relationship are rare. The aim was to
      illuminate patients with long-term illness and nurses' experiences of the caring
      relationship. The data were collected from 13 interviews, seven patients and six
      nurses, which were then analysed using an interpretive phenomenological method.
      This study shows patients' and nurses' view of the phenomenon. The findings
      concerning patients' view were identified in themes --'Maintaining dignity' with
      subthemes: using one's own competence and being cared for by the team as well as
      'A feeling of vulnerability' with subthemes: being cared for in a strained
      situation and being exposed, inquiring personal caring relationship. The findings
      concerning nurses' view were identified in the following themes: 'A purposeful
      striving' with subthemes: using one's own competence and being aware of
      limitations as well as 'An arduous compassion' with subthemes: giving care in a
      strained situation and being aware of what is needed. These findings show that
      patients and nurses were aware in their striving for trust through forming a
      caring relationship. Their striving was not enough to result in trust. The
      findings in this study are understood as patients need a personal caring
      relationship which enables the possibility of trust.

PMID- 18036014
TI  - Intercountry adoption and nursing care.
AB  - AIMS AND OBJECTIVES: This paper is based on a Norwegian study that addressed the
      importance of nurses understanding adoptive families' particular needs. The study
      aimed to provide a diverse picture of adoptive families' challenges and
      resources. It addressed adoptive families' experiences with welfare professions,
      particularly public health nurse services, and explored their need for support
      before and after adoption. This paper focuses particularly on challenges
      confronting 'transracial' families. PARTICIPANTS AND METHOD: The qualitative
      research interview was used as the methodological approach. Nine couples of
      adoptive parents, four adoptive mothers, three public health nurses and four
      adult adoptees were interviewed. The analysis process was an ad hoc generation of
      meaning, and the data were systematically reviewed and categorized through an
      intuitive analysis style. RESULTS: The study indicates that adoptive families
      manage their 'most common' challenges on their own, but the informants also spoke
      about a need for professional support and assistance in many cases. Recurring
      themes in the study were challenges linked to 'attachment difficulties',
      'external categorization', 'grief' and 'the meaning of biological heritage and
      roots'. Findings indicate that there is a substantial demand for increased
      knowledge of adoptive families' special needs, not least in the public health
      nurse services; there is also limited knowledge within other welfare professions.
      Nurses particularly need to strengthen their understanding on how external
      categorization affects transracial adoptive families. CONCLUSIONS: The study
      recommendations call for improved follow-up after adoptions. This can be met by
      establishing a special programme for adoptive families at maternity and child
      health centres. In addition, public health nurses can support adoptees in their
      teenage years through individual consultations.

PMID- 18036015
TI  - Encountering the older confused patient: professional carers' experiences.
AB  - THE STUDY'S RATIONALE: Confusion is a common condition among older patients and
      often a fearful experience. Opinions vary as to how to communicate with and care
      for confused patients and professional carers often find the patients' situation
      almost as distressing as the patients' themselves do. AIMS AND OBJECTIVES: The
      aim of this study was to describe professional carers' experiences of their
      encounters with older confused patients. METHODOLOGICAL DESIGN AND JUSTIFICATION:
      Data was collected from interviews with 10 professional carers working on a ward
      specializing in the care of older confused patients. A descriptive
      phenomenological research approach was used to gather knowledge of professional
      carers' experiences of encounters with older confused patients. ETHICAL ISSUES
      AND APPROVAL: A Regional Board of Research Ethics granted ethical permission for
      the study. The appropriate ethical principles were followed. The participants
      were contacted personally and received a letter providing information on the
      study. Written consent was requested before the interview. If needed, the
      participants were able to get in contact with the staff health service for a
      follow-up after the interview. Names or places have been changed in order to
      ensure confidentiality. RESULTS: The encounter with the confused patient is
      experienced as an encounter with an unfamiliar person, where the patients'
      actions and words are unforeseeable and with a lack of immediate trust. The
      essential meaning is further illuminated by the meaning constituents: the
      unforeseeable encounter, always being on guard and using oneself as a tool.
      RELEVANCE TO CLINICAL PRACTICE: This paper focuses on the importance of
      encouraging professional carers to pay attention to the complexity of the
      encounter with the confused patient, reflecting upon their own behaviour within
      these encounters and the importance of knowledge of the patient's preferred
      senses and life stories. Caring for confused patients involves a great
      responsibility where both the professional carers and the patients are vulnerable
      and exposed.

PMID- 18036016
TI  - Patient attitudes, behaviours, and other factors considered by doctors when
      estimating cancer patients' anxiety and desire for information.
AB  - The aim was to describe the patient attitudes, behaviours, and other factors,
      considered by doctors when estimating cancer patients' worry about how the
      disease may develop and the desire for information about the disease and its
      treatment. Data was gathered through semi-structured interviews with 19 doctors
      regarding 29 patients within endocrine oncology and haematology care, and the
      data were analysed by content analysis. The doctors considered the patients'
      verbal expressions, verbal behaviours, questions, body language, and facial
      expressions together with their own professional knowledge and experience, when
      estimating the patients' worry and desire for information. The doctors also
      considered contextual factors, patients' demographical factors, and medical
      situation when estimating the patients' worry, and also when estimating the
      patients' desire for information. The findings illustrate that estimating
      patients' worry and desire for information is a multifaceted and complex task,
      and that doctors consider not only the patients' verbal and nonverbal cues, but
      also factors, such as their own professional knowledge and experience, contextual
      factors, and patients' demographical variables. The findings should be
      communicated to doctors who meet cancer patients in medical consultations in
      order to illuminate the complexity of the medical consultation. The awareness of
      potentially important patient cues and other factors may aid doctors in their
      efforts to gain insight about their patients' emotions and informational needs.

PMID- 18036017
TI  - A dynamic conceptual model of care planning.
AB  - This article presents a conceptual model of the care planning process developed
      to identify the hypothetical links between structural, process and outcome
      factors important to the quality of the process. Based on existing literature, it
      was hypothesized that a thorough assessment of patients' health needs is an
      important prerequisite when making a rigorous diagnosis and preparing plans for
      various care interventions. Other important variables that are assumed to
      influence the quality of the process are the care culture and professional
      knowledge. The conceptual model was developed as a system dynamics causal loop
      diagram as a first essential step towards a computed model. System dynamics
      offers the potential to describe processes in a nonlinear, dynamic way and is
      suitable for exploring, comprehending, learning and communicating complex ideas
      about care processes.

PMID- 18036020
TI  - Can we believe what children tell us?

PMID- 18036021
TI  - Isolated thrombocytopenia in children: thinking beyond idiopathic
      thrombocytopenic purpura and leukaemia.
AB  - The commonest cause of isolated thrombocytopenia in an otherwise well child is
      idiopathic thrombocytopenic purpura (ITP). The inherited thrombocytopenias such
      as Bernard-Soulier syndrome are rare but often misdiagnosed as ITP owing to a
      similar clinical presentation. We describe a child with Bernard-Soulier syndrome
      who presented with isolated thrombocytopenia, mimicking ITP. Features which help
      to differentiate these two conditions are discussed with a brief literature
      review.

PMID- 18036022
TI  - Transplacental metabolic alkalosis.
AB  - We present a newborn with hypochloraemic metabolic alkalosis due to severe
      metabolic alkalosis of his mother. Hypoventilation as a leading symptom resolved
      quickly with treatment but may be life-threatening if not detected. In this case,
      the mother had a probable eating disorder. Little is known about transplacentally
      acquired electrolyte disorders in this setting. In the absence of symptoms, most
      of the cases might be undetected. The usual neonatal outcome of anorexia and/or
      bulimia nervosa in pregnancy is a lower birthweight and a lower risk for
      instrumental delivery.

PMID- 18036023
TI  - Pulmonary actinomycosis and skin sinuses.
AB  - A 12-year old girl presented with an unusual problem of recurrent discharging
      multiple skin sinuses on her right anterior and posterior chest wall for a year.
      There was ipsilateral lower lobe pneumonia and imaging showed multiple abscesses
      in her lower back muscles bilaterally. A purulent fluid was aspirated from her
      back muscles and the histology examination showed sulphur granules with gram
      positive branched filaments. She responded well to the treatment for
      actinomycosis with penicillin and doxycycline.

PMID- 18036024
TI  - 'Burn off' burns in children.

PMID- 18036025
TI  - The role of calcimimetics in the treatment of hyperparathyroidism.
AB  - Calcimimetics reduce serum levels of parathyroid hormone (PTH) and calcium, with
      a leftward shift in the set-point for calcium-regulated PTH secretion. The aim of
      this publication is to review the data available for calcimimetics in primary,
      secondary and tertiary hyperparathyroidism (HPT). Parathyroidectomy (PTX) is
      currently the only curative treatment for primary HPT, and recommended for
      patients with moderate-to-severe disease, as defined by a 2002 National
      Institute's of Health summary statement. In general, patients with primary HPT
      not meeting these surgical criteria, as well as those with contraindication or
      refusal for surgery, are monitored for signs and symptoms of primary HPT. There
      are currently no non-surgical therapies approved for use in primary HPT, although
      bisphosphonates are used in some patients, in an effort to control serum calcium
      levels. Calcimimetics decrease PTH and calcium levels and are a potential
      alternative for patients contraindicated for PTX, or who have failed previous PTX
      and have recurrent primary HPT. Secondary HPT develops early in chronic kidney
      disease and is present virtually in all patients with end-stage renal disease
      (ESRD). Secondary HPT is a progressive disease and is associated with several
      systemic complications, including renal osteodystrophy, soft tissue and vascular
      calcifications, and adverse cardiovascular outcomes. In ESRD patients,
      calcimimetics were shown to simultaneously reduce PTH, calcium, phosphate and
      calcium x phosphate product. In addition, observational analyses of use of
      calcimimetics in the ESRD population have shown a reduction of important clinical
      outcomes. In renal allograft recipients with tertiary HPT and hypercalcaemia,
      calcimimetics are a promising treatment option to control the parameters of
      calcium phosphate metabolism and may be a valid alternative to PTX. Based on its
      unique mechanism of action, the calcimimetic cinacalcet may play a role in the
      medical treatment of primary and tertiary forms of HPT, in addition to the
      registered indication for the treatment of secondary HPT.

PMID- 18036028
TI  - Assessing risk of myocardial infarction and stroke: new data from the Prospective
      Cardiovascular Munster (PROCAM) study.
AB  - OBJECTIVES: Based on the data of the Prospective Cardiovascular Munster (PROCAM)
      study, a prospective study of men and women at work in the north-west of Germany,
      we aimed (i) to develop a refined scoring scheme for calculating the risk of
      acute coronary events among adult and elderly men and women; and (ii) to generate
      a new scoring scheme for calculating the risk of ischaemic stroke or transient
      ischaemic attack (TIA). METHODS: The coronary risk score was derived from a
      Weibull function using data from 18 460 men and 8515 women who were recruited
      before 1996 and had a mean follow-up period of 12+/-6 years. The stroke score was
      derived using a Cox proportional hazards model using data of 5905 men and 2225
      women aged 35-65 years with at least 10 years of unbroken follow-up. RESULTS: The
      coronary risk score was based on 511 major coronary events, 462 (168 fatal, 294
      non-fatal) in men and 49 (18 fatal, 31 non-fatal) in women and included the risk
      factors LDL cholesterol, HDL cholesterol, systolic blood pressure, smoking
      status, triglycerides and diabetes mellitus status. It was accurate in both sexes
      over an age range from 20 to 75 years with an area under the receiver-operating
      characteristics (ROC) curve of 0.82. The stroke score was based on 85 cerebral
      ischaemic events (21 TIAs, 64 ischaemic strokes) and included the risk factors
      age, sex, diabetes mellitus status, smoking status and systolic blood pressure.
      It had an area under the ROC curve of 0.78 and identified a high-risk group
      comprising only 4% of the study population that contained 31% of all cerebral
      ischaemic events. CONCLUSION: Both new PROCAM risk scores provide simple and
      effective ways to assess the risk of acute coronary events and ischaemic stroke
      in the general population and will improve the ability of physicians to target
      measures in an effort to prevent these potentially devastating conditions.

PMID- 18036029
TI  - Risk management of renal biopsy: 1387 cases over 30 years in a single centre.
AB  - BACKGROUND: Although renal biopsy is largely employed, even in old patients with
      systemic diseases, few clinical studies have addressed its risk management. We
      aimed to obtain a comprehensive assessment of safety/utility ratio of
      percutaneous renal biopsy. PATIENTS AND METHODS: Retrospective review of all the
      1387 patients who consecutively underwent renal biopsy in a single centre over
      three decades (1973-2002) was made, with calculation of complications,
      multivariate logistical analyses to evaluate risk factors of complications, and
      rate of alteration of clinical hypotheses by pathological diagnosis. RESULTS:
      There were no deaths and five major complications, (0.36%). One nephrectomy
      (0.07%), two surgical revisions (0.1%) and two arterial-venous fistulae (0.1%).
      There were also 337 minor bleeding complications (24.2%) (16.4% gross haematuria
      and 7.8% clinically relevant haematomas needing at least prolonged bed rest).
      Multivariate analyses demonstrated that the risk for complications was
      significantly increased by systemic autoimmune diseases with odds ratio (OR)
      2.06, 95% confidence interval (CI)=1.40-3.01, end-stage kidney/acute-tubular
      necrosis (OR 2.96, 95% CI=1.19-7.30), and prolonged bleeding time test (BTT) (OR
      1.87, 95% CI=1.17-2.83). Among the 1288 cases in which a clinical hypothesis
      before renal biopsy was recorded, renal pathology changed previous diagnoses in
      423/1,288 (32.8%) of cases. CONCLUSIONS: Risk assessment demonstrates that renal
      biopsy is a useful procedure with a low incidence of serious complications.
      Platelet function is the only modifiable factor significantly related to bleeding
      complications, suggesting the need for a more standardized alternative to the
      BTT. Platelet function should be evaluated to select low-risk patients for renal
      biopsy as 'a day case procedure', in order to build adequate risk management
      strategies.

PMID- 18036030
TI  - Autonomic cardiovascular regulation in quiescent ulcerative colitis and Crohn's
      disease.
AB  - BACKGROUND: In inflammatory bowel diseases, changes in autonomic enteric
      regulation may also affect neural cardiovascular control. However, while cardiac
      autonomic modulation has been shown to be impaired in active ulcerative colitis,
      the occurrence of cardiovascular autonomic alterations, also in the quiescent
      phase of inflammatory bowel diseases, is still a matter of debate. The aim of our
      study was thus to explore the features of cardiovascular autonomic regulation in
      ulcerative colitis and Crohn's disease during their remission phase. MATERIALS
      AND METHODS: Autonomic cardiovascular control was evaluated by time- and
      frequency-domain indexes of spontaneous heart rate and blood pressure variability
      and by assessing the baroreflex heart rate control (sequence technique) in 26
      patients with ulcerative colitis, in 26 patients with Crohn's disease and in 23
      healthy controls. RESULTS: The groups were matched for age, gender and body mass
      index. They had similar blood pressure mean levels and variability. By contrast,
      mean heart rate, its overall variability (standard deviation), and baroreflex
      sensitivity were lower in ulcerative colitis patients than in controls. Moreover,
      all indexes related to cardiac vagal control were significantly lower in
      ulcerative colitis patients with respect not only to controls but also to Crohn's
      disease patients. CONCLUSIONS: Cardiac vagal control is impaired in quiescent
      ulcerative colitis only, and not in Crohn's disease, while in both bowel diseases
      vascular control appears preserved. Since cardiovagal modulation seems related to
      anti-inflammatory mechanisms, the reduced parasympathetic cardiac regulation in
      apparently quiescent ulcerative colitis suggests that such systemic derangement
      is accompanied by local subclinical inflammations, even in the absence of
      clinically active inflammatory processes.

PMID- 18036031
TI  - Haemodialysis induces mitochondrial dysfunction and apoptosis.
AB  - BACKGROUND: Mitochondria play a crucial role in the regulation of the endogenous
      pathways of apoptosis activated by oxidant stress. Nuclear factor-kappaB (NF
      kappaB) is a central integration site for pro-inflammatory signals and oxidative
      stress. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) were
      isolated from eight end-stage renal disease (ESRD) patients before haemodialysis
      (Pre-HD) and during the last 10 min of HD (End-HD). A new polysulfone membrane
      (F70, Fresenius) was used for dialysis. Intracellular generation of reactive
      oxygen species (ROS), mitochondrial redox potential (Deltapsim) and PBMC
      apoptosis were determined by flow-cytometry. RESULTS: Plasma levels of
      interleukin-6 (IL-6) (24.9+/-7.0 vs. 17.4+/-5.5 pg dL(-1), P<0.05), IL-6 soluble
      receptor (52.2+/-4.9 vs. 37.6+/-3.2 ng dL(-1), P<0.02) and IL-6 gp130 (405.7+/
      41.0 vs. 235.1+/-38.4 ng dL(-1), P<0.02) were higher end-HD compared to pre-HD.
      IL-6 secretion by the isolated PBMC (24.0+/-2.3 vs. 19.3+/-3.5 pg dL(-1), P<0.02)
      increased end-HD. Percentage of lymphocytes exhibiting collapse of mitochondrial
      membrane potential (43.4+/-4.6% vs. 32.6+/-2.9%, P<0.01), apoptosis (33.4+/-7.1%
      vs. 23.7+/-7.7%, P<0.01), and generation of superoxide (20.7+/-5.2% vs. 12.5+/
      2.9%, P<0.02) and hydrogen peroxide (51.1+/-7.8% vs.38.2+/-5.9%, P<0.04) were
      higher at end-HD than pre-HD. NF-kappaB activation (3144.1+/-208.1 vs. 2033.4+/
      454.6 pg well(-1), P<0.02), expression of B-cell lymphoma protein-2 (6494.6+/
      1461 vs. 3501.5+/-796.5 ng mL(-1), P<0.03) and heat shock protein-70 (9.81+/-1.47
      vs. 6.38+/-1.0 ng mL(-1), P<0.05) increased during HD. CONCLUSIONS: Intra
      dialytic activation of cytokines, together with impaired mitochondrial function,
      promotes generation of ROS culminating in augmented PBMC apoptosis. There is
      concomitant activation of pathways aimed at attenuation of cell stress and
      apoptosis during HD.

PMID- 18036032
TI  - Cytomegalovirus hyperimmunoglobulin: mechanisms in allo-immune response in vitro.
AB  - BACKGROUND: Cytomegalovirus hyperimmunoglobulin (CMVIg) containing drugs are
      routinely administered in cardiac transplantation for prophylaxis against CMV
      disease. Yet little is known about their influence on transplant relevant immune
      functions. The aim of this study was to evaluate the effect of CMVIg on cellular
      immunity in in vitro experiments and to define their role in tolerance inducing
      mechanisms. MATERIALS AND METHODS/RESULTS: CMVIg reduces proliferation in mixed
      lymphocyte reactions and anti-CD3 blastogenesis assays and is related to
      decreased production of immune modulating cytokines interleukin (IL)-2,
      interferonr (IFNgamma), IL-10. This antiproliferative effect is associated with a
      cell-cycle arrest in the G0/G1 phase and induction of apoptosis in CD8+ and
      natural killer cells. Co-incubation with CMVIg causes down-regulation of cell
      bound immunoglobulin and FcgammaRIII surface expression on natural killer cells
      and leads to attenuation of antibody dependent cellular cytotoxicity effector
      functions. CONCLUSIONS: We conclude that CMVIg induces immunological features on
      leukocytes in vitro that are known to be related to tolerance induction. Our
      observations extend the current concept of CMVIg as passive CMV prophylaxis to a
      therapeutic drug compound capable of reducing allogeneic immune response.

PMID- 18036033
TI  - The quantitative analysis of peripheral blood FOXP3-expressing T cells in
      systemic lupus erythematosus and rheumatoid arthritis patients.
AB  - BACKGROUND: Expressed in naturally occurring CD4+CD25+ regulatory T cells, FoxP3
      plays an important role in maintaining immune tolerance. We therefore evaluated
      the possibility that the peripheral blood FOXP3+ T-cell deficiency is associated
      with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). MATERIALS
      AND METHODS: The FOXP3 expression in peripheral blood T cells were evaluated and
      correlated to the CD4 and CD25 expression by flow cytometric analysis. Cell
      frequencies of FOXP3+ T cells among CD4+ T cells and absolute FOXP3+ T cell
      counts in SLE and RA patients were determined for the statistical comparison with
      those in normal controls, and their correlation with disease activities in SLE
      patients was evaluated. The FOXP3 transcript levels in peripheral blood
      mononuclear cells (PBMCs) were also determined to correlate the FOXP3+ T-cell
      quantity and to evaluate the possible dysregulation in the expression of two
      FOXP3 mRNA variants in patients. RESULTS: SLE patients had the higher FOXP3+ T
      cell frequency and absolute CD4+CD25-FOXP3+ cell count than normal individuals,
      and the frequencies of CD4+CD25+FOXP3+ and CD4+FOXP3+ cells were positively
      correlated with the disease activities in SLE patients. In contrast, the
      differences in frequencies and absolute counts of FOXP3+ T cells between normal
      controls and RA patients were found to be insignificant. Moreover, SLE and RA
      patients appear to express two FOXP3 transcript variants in peripheral blood
      mononuclear cells at the levels similar to normal individuals. CONCLUSIONS: The
      peripheral blood FOXP3+ T-cell frequency among CD4+ T cells is altered in SLE
      patients with the active disease activity. Therefore, the analysis on peripheral
      blood FOXP3+ T cells may be useful for the evaluation of lupus disease activity.

PMID- 18036034
TI  - Specific allergen enhances IgE production via galectin-3 in surface IgE+ B cells.

PMID- 18036035
TI  - Radial pressure waveform dP/dt max and left ventricular systolic function.

PMID- 18036037
TI  - Our experience with third renal transplantation: results, surgical techniques and
      complications.
AB  - BACKGROUND: Despite the popularity of kidney transplantation in the current era,
      second and third kidney transplantation are not yet widely accepted and
      practiced. Each center has its own regulations and experiences and there is no
      accepted protocol for third kidney transplantation. We report here our 15 years
      of experience with third kidney transplantation. METHODS: This is a report of all
      the third kidney transplantations performed in Baqiyatallah Hospital, Tehran,
      Iran, between 1991 and 2006. Demographic data, surgical techniques, complications
      and outcomes are reported. RESULTS: Of the nine third kidney transplant patients,
      six were male. The median age was 43 years (32-52). All of the patients received
      kidney from living donors. All operations were performed by a midline incision
      and the grafts were placed at the midline, in the intraperitoneal space. For
      arterial anastomosis, we used internal iliac, right common iliac and both the
      right external iliac and inferior mesenteric artery in 4, 4 and 1 case(s),
      respectively. For venous anastomosis, we used vena cava, common iliac and
      external iliac veins in 3, 5 and 1 case(s), respectively. During the follow up
      period (38 months), 6 grafts (66.6%) were functioning. None of the graft
      rejections were due to surgical complications. Wound dehiscence occurred in two
      patients. No other surgical complications including infection, lymphocele or
      hemorrhage were observed. CONCLUSION: Third kidney transplantation is a field
      that has not been fully explored. The rate of complications seems to be not much
      higher than the first transplantation. Defining a standard protocol seems
      necessary.

PMID- 18036039
TI  - Association of vitamin D receptor gene Taq I polymorphism with recurrent
      urolithiasis in children.
AB  - OBJECTIVE: Urolithiasis has a strong familial component. However, to date, no
      specific genetic abnormality has been identified. It has been reported that
      allelic variation in the vitamin D receptor (VDR) gene may affect calcium
      absorption and excretion. Urolithiasis is a multifactorial disease in which both
      genetic and environmental factors have an effect on onset and severity of
      disease. In the present study, the role of Taq I polymorphism of vitamin D
      receptor gene in urolithiasis was studied. METHODS: Eighty children with calcium
      stone disease (40 with single episode of stone disease and 40 with recurrence)
      and 40 controls were enrolled. Polymorphic sites were amplified by polymerase
      chain reaction, digested with Taq I restriction enzymes and analyzed by gel
      electrophoresis. Allelic or genotypic frequencies were calculated and
      associations between them and the presence of hypercalciuria, family history and
      stone recurrence were evaluated. RESULTS: Incidence of Taq I tt genotypes was
      significantly higher in patients with recurrent calcium-stone disease compared to
      the controls. In addition, the frequency of the 't' allele was higher in
      recurrent calcium-stone formers. Taq I t allele was found to be associated with
      increased risk of recurrence. No association between Taq I polymorphism and a
      positive family history was found in the present study. The frequency of
      hypercalciuria was higher in patients with the 'tt' genotype. CONCLUSION: Taq I t
      allele of the VDR gene may be a risk factor for severe urolithiasis and recurrent
      stone disease.

PMID- 18036040
TI  - Surgical treatment for ureterocele with special reference to lower urinary tract
      reconstruction.
AB  - OBJECTIVES: We reviewed the results of surgical treatment for children with
      ureterocele, especially addressing the importance of the lower urinary tract
      reconstruction. METHODS: We present medical records of 91 children with
      ureterocele (31 with the intravesical type, and 60 with the ectopic type) treated
      during the last 14 years. As the initial treatment, we carried out transurethral
      incision of the ureterocele (TUI). In patients with persistent reflux,
      breakthrough urinary tract infection (UTI), or signs of bladder outlet
      obstruction due to a collapsed cele wall, we recommended that patients undergo
      lower urinary tract reconstruction irrespective of the renal function involved in
      ureterocele. The average follow-up period was 5 years (ranging 1 year and 6
      months to 14 years). RESULTS: Transurethral incision of the ureterocele was
      carried out as the initial treatment on 68 patients (75%). A total of 34 patients
      (21 intravesical [68%] and 13 ectopic [22%]) were followed medically after TUI
      alone. Reconstruction of the lower urinary tract was carried out in 59 patients
      (65%). Nephroureterectomy combined with bladder level reconstruction was carried
      out in four children with single system and non-functioning kidney. Follow-up
      voiding cystourethrography showed that only one girl had reflux, which
      disappeared after the first follow-up examination. Postoperative UTI occurred in
      12 patients (20%) with ectopic ureterocele. Voiding dysfunction was suspected in
      eight patients. CONCLUSION: We believe that the primary objective for patients
      with ureterocele, especially of the ectopic type, is to reconstruct the original
      pathology of the lower urinary tract that may give rise to reflux, obstruction,
      or abnormalities of urination. Although surgery at the bladder level can be
      challenging, the lower urinary tract reconstruction successfully corrects the
      vesicoureteral reflux and bladder outlet pathology under a cosmetically
      acceptable incision.

PMID- 18036041
TI  - Recent trends in patient characteristics and therapeutic choices for interstitial
      cystitis: analysis of 282 Japanese patients.
AB  - OBJECTIVES: We investigated the characteristics of recent male and female
      patients diagnosed with interstitial cystitis (IC), then investigated which
      therapy was chosen by the attending urologist. METHODS: Materials were 282 IC
      patients diagnosed and treated during the past 3 years (sampling from Japanese IC
      database). Gender, age, medical history and predominant symptoms were
      investigated. In addition, we investigated the interval before a diagnosis was
      established. In laboratory findings, we investigated voided volume, urinalysis
      findings and cystoscopic findings. Regarding therapy, we investigated which
      therapy was chosen as the first line. RESULTS: The gender ratio was about 1.0:5.6
      (male : female). Regarding age distribution, patients in their 60s were the most
      frequent (65 cases, 31.3%). The interval before diagnosis of IC was 36.5 months
      on average (1-360 months). Regarding medical history, intrapelvic surgery was the
      most common and repeated urinary tract infection was next. The most frequent
      symptom was urinary frequency (295 cases, 98.3%). Urinary urgency was noted in
      186 cases (62%) and supra-pubic pain was noted in 125 cases (41.6%). The once
      voided volume was 104.3 mL on average (50-200 mL). The most common cystoscopic
      finding was glomerulation (158 cases). Ulcer was present in only 19 cases. The
      most widely carried out therapy was hydrodistension (208 cases, 67.9%). Oral
      suplatast tosilate (197 cases, 65.6%), antihistamine (77 cases, 25.6%) and
      intravesical dimethylsulfoxide (69 cases, 23%) followed. CONCLUSIONS: Regarding
      characteristics, the age distribution was older than other countries. The most
      frequent symptom was urinary frequency. Oral suplatast tosilate was one of the
      popular therapies in Japan.

PMID- 18036042
TI  - Preventive effect of risedronate on bone loss in men receiving androgen
      deprivation therapy for prostate cancer.
AB  - AIM: Androgen-deprivation therapy for prostate cancer decreases bone mineral
      density and increases the risk of fracture. The effect of risedronate, a potent
      third-generation oral bisphosphonate, on bone loss during androgen deprivation
      therapy was investigated. METHODS: Sixty-one prostate cancer patients with a mean
      age (+/- SD) of 79 +/- 6 years who had received androgen deprivation therapy for
      42 +/- 29 months were enrolled, and were treated with 2.5 mg of risedronate daily
      for six months. Bone mineral density was measured at the femoral neck, lumbar
      spine, and ultradistal radius by dual energy X-ray absorptiometry. The percent
      change of bone mineral density after treatment with risedronate was calculated as
      the primary efficacy variable. Urinary N-telopeptide of type I collagen was
      measured as a bone resorption marker. RESULTS: Bone mineral density remained
      stable in the femoral neck and radius during risedronate therapy. In contrast,
      the bone mineral density of the lumbar spine showed a significant increase from
      1069 +/- 488 mg/cm(2)-1112 +/- 497 mg/cm(2) (P < 0.001), representing a gain of
      4.9 +/- 8.9%. Urinary N-telopeptide of type I collagen decreased significantly (P
      < 0.001) after three months of risedronate treatment. CONCLUSIONS: Risedronate
      could prevent and reverse bone loss in men receiving androgen deprivation therapy
      for prostate cancer by inhibiting bone resorption.

PMID- 18036043
TI  - Clinical and urodynamic outcomes of pubovaginal sling procedure with autologous
      rectus fascia for stress urinary incontinence.
AB  - AIM: We report the clinical and urodynamic outcomes of the pubovaginal sling
      procedure with autologous rectus fascia for stress urinary incontinence (SUI) and
      determined the urodynamic parameters that could predict the occurrence of
      postoperative voiding difficulty. METHODS: Between 1998 and 2005, a total of 29
      consecutive women with SUI underwent pubovaginal sling surgery with autologous
      rectus fascia. Patients were preoperatively and postoperatively evaluated with
      regard to symptoms and urodynamic findings including uroflowmetry (UFM), postvoid
      residual urine volume (PVR), filling cystometry (CMG) and pressure flow study
      (PFS). RESULTS: Overall SUI was cured in 23 patients (80%) and improved in 3
      patients (10%). Three patients (10%) who developed persistent urinary retention
      or severe voiding difficulty after surgery underwent urethrolysis. Of 17 patients
      who had urgency before the pubovaginal sling, urgency was cured postoperatively
      in seven, while de novo urgency appeared in one patient. Maximum flow rate (Qmax)
      in UFM was significantly decreased (P < 0.05) and PVR was increased (P = 0.08)
      after surgery. PFS showed a significant increase in detrusor opening pressure and
      detrusor pressure at Qmax (P < 0.01) after surgery. Eight patients (28%) needed
      prolonged intermittent self-catheterization. Patients who had PVR >100 mL (P <
      0.05) or Qmax < or = 20 mL/s (P = 0.09) in preoperative UFM were more likely to
      require prolonged intermittent catheterization after surgery. CONCLUSIONS: The
      pubovaginal sling procedure with autologous rectus fascia is an effective
      treatment for SUI. A comparison of preoperative and postoperative urodynamic
      parameters indicates an increase in urethral resistance after pubovaginal sling
      surgery. PVR >100 mL and Qmax < or = 20 mL/s before surgery are risk factors for
      postoperative voiding difficulty.

PMID- 18036044
TI  - Effect of microsurgical repair of the varicocele on testicular function in
      adolescence and adulthood.
AB  - OBJECTIVE: Many reports on varicoceles suggest improved spermatic findings and
      increased pregnancy rates after correction of these lesions. Early repair during
      adolescence has been advocated, since clinically apparent varicoceles may affect
      testicular volume and sperm production in the future. We examined the efficacy of
      microsurgical varicocelectomy, and aimed to establish predictive parameters
      useful for ascertaining whether varicocele repair provides any benefits in
      adolescents and adults. METHODS: We carried out microsurgical varicocelectomy on
      nine boys and 19 men. In adolescents, catch-up growth of the testis, expressed by
      pre- and postoperative ratios of left and/or right testicular volume, grade and
      serum level of follicle-stimulating hormone (FSH) were evaluated. In adults, the
      ratio of sperm concentration improvement, grade, testicular volume, preoperative
      sperm concentration and serum FSH level were evaluated. All subjects were
      followed for 12 months. RESULTS: Catch-up growth was seen in 62.5% of boys. FSH
      level was significantly lower in boys with catch-up growth than in boys without
      catch-up growth. Improved sperm concentration was seen in 73.6% of adults. FSH
      level was significantly lower in adults with improved sperm concentration than in
      patients without improved sperm concentration. No correlations were seen between
      other parameters and catch-up growth in adolescents, or sperm concentration
      improvement in adults. CONCLUSIONS: Microsurgical varicocelectomy as a treatment
      for varicoceles with low FSH might be effective and the relevant predictive
      parameter for testicular development and function after surgery might be serum
      FSH level in both adults and adolescents.

PMID- 18036045
TI  - Overexpression of p27kip1 in urinary bladder urothelial carcinoma.
AB  - OBJECTIVES: Cyclins and cyclin-dependent kinase (CDK) complexes have important
      regulatory roles during cell cycle progression and can be used as prognostic
      markers in various kinds of malignant tumors. This study investigated the
      expression of proliferative cell nuclear antigen (PCNA), p53, Rb, p27(kip1), and
      cyclin D1 by immunostains in bladder tumors, especially urothelial papilloma,
      papillary urothelial neoplasm of low malignant potential, and low and high grade
      urothelial carcinoma, to see if their expression is associated with
      classification or grading of the urinary bladder urothelial carcinoma. METHOD:
      Nuclear expression of PCNA, p53, Rb, p27(kip1), and cyclin D1 was determined
      immunohistochemically in a series of 89 urinary bladder tumor specimens,
      including 13 papilloma, 15 urothelial neoplasm of low malignant potential, 17 low
      grade urothelial carcinoma, and 44 high grade urothelial carcinoma. The results
      of immunoreactivity were analyzed with respect to the associations with tumor
      grade. RESULTS: Eighty-two percent (38/45) of the p27(kip1) positive tumors were
      urothelial carcinoma, and the percentage of the p27(kip1) positivity was higher
      with increasing grade of the urothelial carcinoma (P = 0.011). A tendency of
      higher percentage of positive p53 immunoreactivity was noted in the urothelial
      carcinoma (P = 0.053). There was no significant difference in cyclinD1, Rb and
      PCNA expression between benign, low malignant potential and urothelial carcinoma.
      CONCLUSION: We first noted an overexpression of p27(kip1) in urinary bladder
      urothelial carcinoma. The result indicates that some urothelial carcinomas may
      tolerate this inhibitor of cell cycle progression.

PMID- 18036046
TI  - Expression of aquaporin 3 in the human prostate.
AB  - OBJECTIVE: Aquaporins (AQPs) function as selective pores allowing water, glycerol
      and other small solutes to pass through the cell membrane. The present study
      investigated the expression and localization of AQP3 in the human prostate.
      METHODS: Three human prostate cancer cell lines (DU-145, LNCaP and PC-3) and one
      normal human prostate cell line (PNT1A) were used in this study. Clinical
      materials from patients with prostate cancer were also used. AQP3 mRNA and
      protein expression were examined using reverse transcription-polymerase chain
      reaction and immunohistochemical methods. RESULTS: Aquaporin 3 mRNA was expressed
      in normal and cancerous prostate cells. Moreover, the expression of AQP3 mRNA was
      seen in both normal and cancerous epithelia of human prostate tissues, but not in
      the mesenchyme. In the normal epithelia of the prostate, localization was limited
      to cell membranes, particularly the basolateral membranes. However, the
      expression of AQP3 protein in the cancer epithelia was not observed on the cell
      membranes. CONCLUSION: The results suggest that water-channel protein may be
      involved in the preservation of cellular character in the human prostate and
      prostate cancer is associated with an alteration of water-transporting
      mechanisms. Changes in the localization of AQP3 in cancer cells may result from
      tumorigenesis.

PMID- 18036048
TI  - Lymphoepithelioma-like carcinoma of the renal pelvis.
AB  - Lymphoepithelial-like carcinoma of the renal pelvis is an extremely rare entity.
      Only four cases involving the renal pelvis have been previously reported. We
      report the fifth case of lymphoepithelioma-like carcinoma of the renal pelvis.

PMID- 18036049
TI  - Pathological evidence of necrosis in recurrent renal mass following treatment
      with sunitinib.
AB  - Sunitinib is a highly potent, selective vascular endothelial growth factor
      receptor types 1 to 3, platelet-derived growth factor (PDGF)-R-alpha, and PDGF-R
      ss. Preclinical data suggest that sunitinib (SU11248) has antitumor activity that
      may result from both inhibition of angiogenesis and direct antiproliferative
      effects on certain tumor cell types. Sunitinib resulted in tumor shrinkage in 80%
      of patients who had failed treatment with Bevacizumab and 13% of patients
      demonstrated an objective Response Evaluation Criteria in solid Tumors (RECIST)
      in a study presented at the 2006 American Society of Clinical Oncology (ASCO)
      meeting. We report the first published pathological evidence of sunitinib's
      effect on recurrent renal cell carcinoma. This was seen in a patient with renal
      cell carcinoma who developed a renal fossa recurrence 2 years following radical
      nephrectomy. Tumor shrinkage was evident in the nephrectomy bed after treatment
      with sunitinib. The pathology of the resected retroperitoneal mass and its
      implications are discussed.

PMID- 18036051
TI  - Rare case of the hyaline vascular type of Castleman's disease of the kidney.
AB  - Castleman's disease (CD) is a rare disorder characterized by a benign
      proliferation of lymphoid tissue. Most cases tend to present as a mediastinal
      mass. A few extrathoracic cases involving nodal and extranodal locations have
      previously been reported. To the best of our knowledge, however, only one case of
      CD of the kidney has been published in an English report. We herein report a rare
      case of CD presenting as a left renal tumor. A 70-year-old male was examined by
      computed tomography for a follow-up for colonic diverticulitis and a left renal
      mass measuring 2.0 cm in diameter was incidentally found. The patient underwent a
      left partial nephrectomy for a left renal mass and a histopathological analysis
      demonstrated the hyaline vascular type of CD. Based on our findings, CD should be
      included in the differential diagnosis of renal tumors.

PMID- 18036052
TI  - Bladder evisceration in a child with antenatally detected gastroschisis: outcome
      of bladder function.
AB  - In patients with gastroschisis, evisceration of the bladder is rare. To date,
      little is known about functional outcome of the antenatally eviscerated bladder.
      We present a case of antenatally detected gastroschisis associated with entire
      bladder evisceration and fetal hydronephrosis. Full urological evaluation was
      carried out after primary closure of the abdominal wall defect. The postoperative
      period was uneventful and there were no abnormal findings in the kidney or
      urinary tract. This indicated good prognosis of the antenatally eviscerated
      bladder.

PMID- 18036053
TI  - Carbohydrate antigen 19-9-positive prostatic ductal adenocarcinoma effectively
      treated with cisplatin and gemcitabine.
AB  - We performed a radical retropubic prostatectomy on a 59-year-old male patient who
      was diagnosed with prostatic carcinoma. Pathological findings revealed a ductal
      adenocarcinoma in the left lobe of the prostate, and a conventional well
      differentiated adenocarcinoma in the right lobe. Immunohistochemistry revealed
      that CA19-9 was positive in the ductal adenocarcinoma, and prostate-specific
      antigen was positive in the conventional well-differentiated adenocarcinoma.
      Since there was an increase in the level of serum CA19-9, which had decreased
      postoperatively, along with the appearance of local recurrence and bone
      metastasis, we treated the patient with cisplatin and gemcitabine. As a result,
      the level of serum CA19-9 was normalized and a reduction of the metastatic focus
      was observed.

PMID- 18036054
TI  - Post-surgical high-flow priapism treated by embolization.
AB  - Perineal and penile traumas are the commonest cause of high-flow priapism. The
      clinical symptom of this disease is generally a prolonged, painless, and
      semirigid penile erection without any other urogenital symptoms. In contrast,
      high-flow priapism is a quite uncommon condition after transurethral surgery and
      it may be presented with an unusual clinical manifestation. Herein, we report the
      first case of priapism associated with massive urethral hemorrhage requiring
      blood transfusion after internal urethrotomy. High-flow priapism was successfully
      treated by autologous clot embolization and the priapism associated with massive
      urethral hemorrhage resolved.

PMID- 18036055
TI  - Sequential bilateral minimum incision endoscopic radical nephrectomy in dialysis
      patients with bilateral renal cell carcinomas.
AB  - Since 1998, we have performed minimum incision endoscopic surgery (MIES) for
      renal cell carcinoma (RCC). For seven dialysis patients with bilateral RCC, we
      have performed sequential bilateral MIES radical nephrectomy. It was carried out
      by retroperitoneal approach through a single minimum incision that narrowly
      permitted extraction of the specimen using endoscopy and direct stereovision,
      without trocar ports, without gas insufflation and without the insertion of the
      hands of operators into the operative field. Although six of the seven patients
      had multiple complications in addition to chronic renal failure (CRF), bilateral
      kidneys were successfully removed by sequential MIES radical nephrectomy without
      major operative complication. Postoperative recovery was prompt with all patients
      resuming oral feeding and walking by the second postoperative day. Sequential
      bilateral MIES radical nephrectomy, leaving the peritoneal cavity intact and
      without imposing circulatory stress caused by gas insufflation, is a feasible
      treatment for bilateral RCCs in dialysis patients.

PMID- 18036056
TI  - Oral calcium supplementation associated with decreased likelihood of
      nephrolithiasis prior to surgery for hyperparathyroidism.
AB  - We aimed to assess the impact of oral calcium supplementation (OCS) on the
      prevalence of nephrolithiasis among a cohort of patients undergoing surgery for
      primary hyperparathyroidism (PHPT). There were 339 patients undergoing surgery
      for PHPT with detailed past medical history data that were analyzed. 73 patients
      (22%) had a history of nephrolithiasis prior to parathyroid surgery.
      Nephrolithiasis was more common among men than women (40% vs 15%, P < 0.001),
      despite the predominance of women (73% of patients) with hyperparathyroidism. 83
      patients (25%) used OCS. OCS was associated with a lower prevalence of
      nephrolithiasis (9.6% vs 25.4% without OCS, P = 0.002). This protective effect
      included both men and women (rates of nephrolithiasis with and without
      supplements: men 19% vs 46%, P = 0.027; women 7% vs 17%, P = 0.04). The mechanism
      for the apparent protective effect of OCS on rates of nephrolithiasis is unclear,
      and further research is required to elucidate the variable penetrance of
      nephrolithiasis among PHPT patients.

PMID- 18036058
TI  - A pediatric perspective: adult problems in kids, new challenges in pediatric
      diabetes.

PMID- 18036057
TI  - The Second Joint Meeting of American Urological Association (AUA)/Japanese
      Urological Association (JUA) International Program on the 102nd Annual Meeting of
      American Urological Association at Anaheim 2007.

PMID- 18036059
TI  - An internist's perspective: type 2 diabetes in childhood and adolescence: what
      does the future hold?

PMID- 18036060
TI  - Family history of diabetes, autoimmunity, and risk factors for cardiovascular
      disease among children with diabetes in the SEARCH for Diabetes in Youth Study.
AB  - BACKGROUND: While type 1 diabetes and type 2 diabetes (T2D) are considered
      etiologically distinct, mixed features of autoimmunity and insulin resistance are
      increasingly common. We explored a familial contribution to this admixture by
      evaluating diabetes family history (FH) and its relationship to diabetes type,
      ethnicity, age at diagnosis, and cardiovascular risk factors in SEARCH for
      Diabetes in Youth Study participants. METHODS: Diabetes FH was assessed by
      questionnaire, with FH categories defined by relative's(s') age at diagnosis as
      follows: <25 (early FH), >/=25 (later FH), and both <25 and >/=25 (mixed FH).
      Diabetes type was classified based on a biochemical algorithm using diabetes
      autoantibodies and fasting C-peptide (FCP). RESULTS: A positive FH was common in
      all diabetes types, particularly T2D (83%). Minorities were more likely to have a
      positive FH than non-Hispanic Whites [odds ratio (OR) 1.96, 95% confidence
      interval (CI) 1.69-2.27]. The likelihood of having an early FH decreased with age
      at diagnosis (OR 0.95, 95% CI 0.93-0.98), and the likelihood of having a
      later/mixed or any positive FH increased with age (OR 1.03, 95% CI 1.01-1.04; OR
      1.03, 95% CI 1.02-1.05, respectively). Higher FCP concentrations and less
      desirable values for almost all cardiovascular risk factors were associated with
      a later/mixed FH. The association between a later/mixed FH and FCP, body mass
      index, waist circumference, triglycerides, and high-density lipoprotein remained
      significant in a subgroup of autoimmune participants. CONCLUSIONS: Later FH
      confers cardiovascular risk factors in diabetic youth, including those youth with
      islet cell autoimmunity. This characterization of diabetes FH may provide a
      better understanding of familial contributors to diabetes.

PMID- 18036061
TI  - Parental fear of hypoglycemia: young children treated with continuous
      subcutaneous insulin infusion.
AB  - BACKGROUND: The objective of this study was to examine the association between
      parental fear of hypoglycemia and average daily blood glucose control of young
      children with type 1 diabetes receiving continuous subcutaneous insulin infusion
      (CSII). We hypothesized that parental fear of hypoglycemia would correlate
      positively with children's average daily blood glucose control. METHODS: Twenty
      four families of children with type 1 diabetes who were receiving CSII were
      recruited from a pediatric hospital. Children had a mean age of 5.7 +/- 1.8 yr
      (range 2-8 yr) and were evenly split on gender. Parents completed a modified
      version of the Hypoglycemia Fear Survey - Parents of Young Children (HFS-PYC), a
      measure designed to assess fear and avoidance behaviors associated with
      hypoglycemia. Blood glucose was assessed for the 2 wk following completion of the
      HFS-PYC using a standard home blood glucose meter. RESULTS: Parents of young
      children obtained a mean total HFS-PYC score of 81 +/- 14.1 (possible range 26
      130), suggesting a moderate level of fear. The HFS-PYC was found to be internally
      consistent and had good test-retest reliability. For parents of young children
      receiving CSII, fear of hypoglycemia correlated positively with children's mean
      daily blood glucose levels (r = 0.41, p = 0.05). CONCLUSIONS: Parents of young
      children with type 1 diabetes who are receiving CSII report significant fear of
      hypoglycemia. Parental fear of hypoglycemia may be a barrier to prevent optimal
      glycemic control.

PMID- 18036062
TI  - Incidence and prevalence of type 1 diabetes in children aged <15 yr in Castilla
      Leon (Spain).
AB  - OBJECTIVES: To determine the incidence and prevalence of type 1 diabetes in
      children younger than 15 yr in the Autonomous Community of Castilla-Leon (Spain).
      RESEARCH DESIGN AND METHODS: All type 1 diabetic cases with onset at <15 yr of
      age were recorded during 2003-2004. Identified case subjects were ascertained
      from several sources and the capture-recapture method was used to estimate the
      completeness of ascertainment. For prevalence, all patients younger than 15 yr
      with type 1 diabetes at the beginning and at the end of the study were
      identified. RESULTS: Over the study period, 130 children aged 0-14 yr were
      diagnosed with type 1 diabetes. The average observed incidence of type 1 diabetes
      in this population was 22.22/100 000/yr (95% CI 14.57-29.81). Age-standardized
      incidence was 22.01/100 000/yr (95% CI 18.18-25.83). The highest incidence was
      observed in the 5-9 yr age-group (32.45/100 000/yr, 95% CI 24.31-40.59). The
      prevalence at the beginning and at the end of the study was 1.01/1000 and
      1.18/1000, respectively. CONCLUSION: Castilla-Leon appears to have one of the
      highest incidences of childhood type 1 diabetes in Spain, with recent incidence
      approaching those of some northern European countries.

PMID- 18036063
TI  - Rising incidence of type 1 diabetes mellitus in children and adolescents in
      Cyprus in 2000-2004.
AB  - INTRODUCTION: The incidence of type 1 diabetes mellitus (T1DM) has dramatically
      increased recently in some countries. AIM: To ascertain any changes in the
      incidence of T1DM in our population during the years 1990-2004. METHODOLOGY: All
      newly diagnosed cases of T1DM children under the age of 15 yr were registered and
      relevant information was obtained. Population demographic data based on the most
      recent census were used for calculations. RESULTS: The overall mean annual
      incidence of T1DM during this 15-yr period was 11.9/100,000 person-years, with a
      statistically significant increase in the third 5-yr period (14.9/100,000 person
      years). The incidence during the first (1990-1994) and second (1995-1999) 5-yr
      periods was 10.5/100,000 person-years (p < 0.001). The overall male:female ratio
      was 0.94. Seasonal distribution for the first and second 5-yr periods revealed a
      higher incidence during winter and autumn months. Seasonal variation, however,
      disappears in the third 5-yr period, where no differences were found between the
      four seasons. CONCLUSION: The incidence of newly diagnosed T1DM cases has
      increased during 2000-2004. A seasonal variation during the first and second 5-yr
      periods was no longer observed in the third 5-yr period.

PMID- 18036065
TI  - Dyslipidemia and other cardiovascular risk factors in a Canadian First Nation
      pediatric population with type 2 diabetes mellitus.
AB  - OBJECTIVE: The objectives of this study were to describe the prevalence of
      dyslipidemia in a population of youth with type 2 diabetes mellitus (T2DM) and to
      examine the relationship between the lipid parameters and other known
      cardiovascular risk factors. METHODS: Ninety-nine youth aged 7-17 yr with T2DM
      had a fasting blood sample for lipid and lipoprotein levels [total cholesterol,
      low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein
      cholesterol, triglycerides (TG)], apolipoprotein B (apoB), blood glucose, and
      hemoglobin A1c (HbA1(C)). Lipid profiles were compared with a non-diabetic
      population of Canadian First Nation (FN) youth and to published reference data.
      Rates of obesity, hypertension, smoking, and poor glycemic control were recorded
      and the relationship between these cardiovascular risk factors and lipid patterns
      was analyzed. RESULTS: Fifty-seven percent of the subjects were female and 95%
      were of self-declared FN heritage. The mean levels of all components of the lipid
      profile were elevated in the group with T2DM compared with the control population
      (p < 0.001). ApoB levels exceeded the 75th %ile of the control population in 72%
      of those with T2DM. Thirty-seven percent of those with T2DM had elevated TG and
      apoB levels. Forty percent were smokers. Fifty-nine percent had an HbA1(C) that
      was greater than 7.0%. Thirty-nine percent had a BMI z-score >/= 2 but less than
      15% had systolic hypertension. CONCLUSIONS: Atherogenic lipid profiles are common
      in youth with T2DM. Elevated apoB levels with normal LDL-c levels highlight the
      importance of a full lipid panel including apoB in defining potential modifiable
      cardiovascular risk in this population with high rates of obesity, smoking, and
      poor glycemic control.

PMID- 18036064
TI  - Continuous subcutaneous insulin infusion benefits quality of life in preschool
      age children with type 1 diabetes mellitus.
AB  - OBJECTIVE: To compare medical, nutritional, and psychosocial outcomes of
      continuous subcutaneous insulin infusion (CSII) therapy and multiple daily
      insulin injections (MDI) in preschoolers with type 1 diabetes mellitus (T1DM) in
      a randomized controlled trial. STUDY DESIGN: Sixteen children (mean age 4.4 +/-
      0.7 yr, range 3.1-5.3 yr) with T1DM were randomly assigned to CSII or MDI.
      Hemoglobin A1c (HbA1c) was measured monthly for 6 months. Glucose variability was
      measured at baseline and at 6 months using continuous blood glucose sensing.
      Quality of life, adverse events, and nutrition information were assessed.
      RESULTS: Parents of the CSII group reported a significant decrease in diabetes
      related worry, while parents of the MDI group reported an increased frequency of
      stress associated with their child's medical care. Mean HbA1c levels from
      baseline (CSII 8.3 +/- 1.4%, MDI 8.0 +/- 0.8%) to 6 months (CSII 8.4 +/- 0.8%,
      MDI 8.2 +/- 0.4%) remained stable, and group differences were not significant.
      There were no significant group differences in duration of hypo- or hyperglycemic
      events or frequency of adverse events. CONCLUSION(S): For young children with
      T1DM, CSII therapy is comparable to MDI therapy with regard to glucose control
      but is associated with higher treatment satisfaction and improved quality of
      life.

PMID- 18036066
TI  - Unexplained hypoglycaemia on a pump.
AB  - A 10-year-old boy on an insulin pump with frequent episodes of hypoglycaemia,
      admitted to administering insulin to cover sweet intake using the pump prime
      function, thereby bypassing the bolus history that his mother monitored. This
      case demonstrates children's resourcefulness and technical abilities, and the
      difficulties parents experience in providing appropriate support.

PMID- 18036067
TI  - Lispro insulin-induced lipoatrophy: a new case.
AB  - Lipoatrophy (LA) is a rare complication of insulin treatment in type 1 diabetes
      mellitus. The pathogenesis of insulin-induced LA is still unknown. Many theories
      suggest immunological reactions. We report a 4-yr-old Saudi girl with LA probably
      induced by lispro insulin. A review of the literature on the clinical features,
      pathophysiology, differential diagnosis, and treatment is briefly discussed.

PMID- 18036068
TI  - Necrotizing fasciitis in adolescents with poorly controlled type 1 diabetes
      mellitus: report of two cases.
AB  - Necrotizing fasciitis (NF) is a potentially fatal bacterial infection of the
      subcutaneous soft tissues. Two cases of polymicrobial NF in adolescents with type
      1 diabetes mellitus and poor glycemic control are reported. The perineal region
      was involved in both cases. One case was precipitated by apparently minimal
      trauma, the other by high-impact trauma. Diabetes mellitus has been identified as
      a common comorbidity and predictor of increased mortality in adult patients with
      NF. The associations between diabetes and the incidence or outcome of NF in
      children and adolescents are not known. In all cases, early identification and
      aggressive surgical intervention are important for limiting morbidity and
      mortality.

PMID- 18036069
TI  - Sick day management in children and adolescents with diabetes.

PMID- 18036070
TI  - Assessment and monitoring of glycemic control in children and adolescents with
      diabetes.

PMID- 18036072
TI  - The consensus development process in transfusion medicine: does it add value?

PMID- 18036073
TI  - Pathogen inactivation: a new paradigm for blood safety.

PMID- 18036074
TI  - Designing laboratory-based research studies: is it time for a change?

PMID- 18036075
TI  - Pathogen inactivation: making decisions about new technologies. Report of a
      consensus conference.

PMID- 18036077
TI  - On residual risk assessment for first-time donation.

PMID- 18036078
TI  - Predicting long-term sickness absence from sleep and fatigue.
AB  - Disturbed or shortened sleep is prospectively related to disease. One might also
      expect that sickness absence would be another consequence but very little data
      seem to exist. The present study used 8300 individuals in a national sample to
      obtain information on reports of disturbed sleep and fatigue one [corrected] year
      and merged this with data on long-term sickness absence two [corrected] years
      later. A logistic regression analysis was applied to the data with adjustments
      for demographic and work environment variables. The results showed that
      individuals without registered sickness absence at the start had a higher
      probability of entering a period of long-term (>/=90 days, odds ratio [OR] = 1.24
      with 95% Confidence Interval [CI] = 1.09[corrected]-2.18[corrected]) sickness
      absence two [corrected] years later if they reported disturbed sleep at the
      start. The value [corrected] for fatigue was OR = 1.69[corrected] (CI =
      1.23[corrected]-2.33[corrected]). When fatigue or disturbed sleep was separately
      excluded the OR increased to OR = 1.90[corrected] and OR = 1.86[corrected],
      respectively. Intermediate sickness absence (14-89 days) showed similar but
      slightly weaker results. The results indicate that disturbed sleep and fatigue
      are predictors of long-term absence and it is suggested that impaired sleep may
      be part of a chain of causation, considering its effects on fatigue.

PMID- 18036079
TI  - When sleep is perceived as wakefulness: an experimental study on state perception
      during physiological sleep.
AB  - While electrophysiologically measured sleep and perception of sleep generally
      concur, various studies have shown this is not always the case. The objective of
      the present study was to assess the perception of actual state during sleep by
      the technique of planned awakenings and interviewing subjects on the preawakening
      state. Sixty-eight (43 females, 25 males) young (mean age: 24.1, SD 5.1 years)
      normal sleeping subjects were deliberately awakened out of consolidated sleep,
      either stage 2 (S2), or REM sleep, during the first night in a non-clinical sleep
      laboratory. While the preawakening state was experienced as sleep in 48 cases
      (70.6%), it was experienced as wakefulness in 20 cases (29.4%). The percentage of
      awake judgements was somewhat, but not significantly, higher for awakenings out
      of S2 (38.2%), to REM sleep (20.6%). The proportion of mismatches between
      electrophysiologically defined sleep and state judgements was time-dependent with
      more awake judgements for REM sleep in the second half of the sleep period
      (41.7%) than in the first one (17.4%). Those subjects who made an awake judgement
      more frequently had a feeling of being aware of the situation and their
      surroundings than those who made a sleep judgement (80% versus 33%). Awareness
      during sleep may be a cognitive style, which favours mismatches between state
      perception and electrophysiologically defined sleep. Sleep periods with
      concordant or discordant state judgements did not differ in
      electrophysiologically defined sleep onset latency, sleep efficiency, or sleep
      state distribution.

PMID- 18036080
TI  - The trait of Introversion-Extraversion predicts vulnerability to sleep
      deprivation.
AB  - According to Eysenck's theory of Introversion-Extroversion (I-E), introverts
      demonstrate higher levels of basal activity within the reticular-thalamic
      cortical loop, yielding higher tonic cortical arousal than Extraverts, who are
      described conversely as chronically under-aroused and easily bored. We
      hypothesized that higher scores on the trait of Extraversion would be associated
      with greater declines in psychomotor vigilance performance during prolonged
      wakefulness. We evaluated the relationship between I-E and overnight psychomotor
      vigilance performance during 77 h of continuous sleep deprivation in a sample of
      23 healthy adult military personnel (19 men; four women), ranging in age from 20
      to 35 years. At baseline, volunteers completed the Revised NEO Personality
      Inventory (NEO PI-R) and completed psychomotor vigilance testing at approximately
      10-min intervals from 00:15 to 08:50 hours over three nights of continuous sleep
      deprivation. In addition, 12 participants received four repeated administrations
      of caffeine (200 mg) every 2 h each night. Analysis of covariance and stepwise
      multiple regression analyses showed that, above and beyond the effects of
      caffeine, higher Extraversion was significantly related to more extensive
      declines in speed of responding and more frequent attentional lapses, but only
      for the first overnight testing session. Sub-factors of Extraversion, including
      Gregariousness and higher Activity level were most predictive of these changes
      following sleep loss. These findings are consistent with Eysenck's cortico
      reticular activation theory of I-E and suggest that individual differences in the
      trait of Extraversion confer some vulnerability/resistance to the adverse effects
      of sleep loss on attention and vigilance.

PMID- 18036081
TI  - Determinants of excessive daytime sleepiness in a French community-dwelling
      elderly population.
AB  - Epidemiological studies have suggested that excessive daytime sleepiness (EDS) is
      associated with depression, but the association between EDS and other psychiatric
      disorders has not been investigated. The aim of this study was to investigate the
      association of EDS with a wide range of psychiatric disorders and health-related
      conditions in the elderly population. Two thousand two hundred and fifty-nine non
      institutionalised persons aged 65-years and over randomly recruited from the
      Montpellier district, France, completed the Epworth Sleepiness Scale (ESS).
      Psychiatric status was assessed by the Mini International Neuropsychiatric
      Interview and demographic and other health information was obtained. This cross
      sectional study was conducted from March 1999 to February 2001. Men were
      significantly more likely to report EDS (ESS score>10) compared with women (12.0%
      versus 6.0% respectively). EDS was significantly associated in univariate
      analyses with chronic diseases, early awakening, snoring, severity of depression
      and lifetime prevalence of manic and hypomanic episodes. A multivariate analysis
      revealed that the lifetime prevalence of manic and hypomanic episodes, snoring
      and gender (male) were independently associated with EDS. No independent
      association with other psychiatric disorders was found.

PMID- 18036082
TI  - Prolonged-release melatonin improves sleep quality and morning alertness in
      insomnia patients aged 55 years and older and has no withdrawal effects.
AB  - Melatonin, secreted nocturnally by the pineal gland, is an endogenous sleep
      regulator. Impaired melatonin production and complaints on poor quality of sleep
      are common among the elderly. Non-restorative sleep (perceived poor quality of
      sleep) and subsequently poor daytime functioning are increasingly recognized as a
      leading syndrome in the diagnostic and therapeutic process of insomnia
      complaints. The effects of 3-weeks prolonged-release melatonin 2 mg (PR
      melatonin) versus placebo treatment were assessed in a multi-center randomized
      placebo-controlled study in 170 primary insomnia outpatients aged > or =55 years.
      Improvements in quality of sleep (QOS) the night before and morning alertness
      (BFW) were assessed using the Leeds Sleep Evaluation Questionnaire and changes in
      sleep quality (QON) reported on five categorical unit scales. Rebound insomnia
      and withdrawal effects following discontinuation were also evaluated. PR
      melatonin significantly improved QOS (-22.5 versus -16.5 mm, P = 0.047), QON
      (0.89 versus 0.46 units; P = 0.003) and BFW (-15.7 versus -6.8 mm; P = 0.002)
      compared with placebo. The improvements in QOS and BFW were strongly correlated
      (Rval = 0.77, P < 0.001) suggesting a beneficial treatment effect on the
      restorative value of sleep. These results were confirmed in a subgroup of
      patients with a greater symptom severity. There was no evidence of rebound
      insomnia or withdrawal effects following treatment discontinuation. The incidence
      of adverse events was low and most side-effects were judged to be of minor
      severity. PR-melatonin is the first drug shown to significantly improve quality
      of sleep and morning alertness in primary insomnia patients aged 55 years and
      older-suggesting more restorative sleep, and without withdrawal symptoms upon
      discontinuation.

PMID- 18036083
TI  - Inhibitory motor control in apneic and insomniac patients: a stop task study.
AB  - The aim of this study was to assess with a stop task the inhibitory motor control
      efficiency--a major component of executive control functions--in patients
      suffering from sleep disorders. Twenty-two patients with untreated obstructive
      sleep apnea syndrome (OSAS) (mean age 46 +/- 9 years; mean apnea-hypopnea index,
      AHI = 30 +/- 20) and 13 patients with psychophysiological insomnia (mean age 47
      +/- 12 years) were compared with individually matched healthy controls. Sleep
      disturbances in the patient populations were clinically and polysomnographically
      diagnosed. The stop task has a frequent visual 'Go' stimulus to set up a response
      tendency and a less frequent auditory 'Stop' signal to withhold the planned or
      prepotent response. The stop signal reaction time (SSRT) reflects the time to
      internally suppress the ongoing response. SSRT was slower for the apneic patients
      than for their respective controls (248 +/- 107 versus 171 +/- 115 ms, anova, P <
      0.05) but not for the insomniac patients compared with their controls (235 +/-
      112 versus 194 +/- 109 ms, NS). Moreover, in apneic patients, slower SSRT was
      associated with lower nocturnal oxygen saturation (r = -0.477, P < 0.05). By
      contrast, neither apneics nor insomniacs differed from their matched controls for
      reaction times on Go trials. To conclude, unlike insomniacs, OSAS patients
      present an impaired inhibitory motor control, an executive function which is
      required in many common everyday life situations. Inhibitory motor control relies
      on the integrity of the inferior prefrontal cortex, which could be affected by
      nocturnal oxyhemoglobin desaturation in apneic patients.

PMID- 18036084
TI  - Structural equation modeling of sleep apnea, inflammation, and metabolic
      dysfunction in children.
AB  - Obstructive sleep apnea (OSA), often concomitant with obesity, increases the risk
      for the metabolic syndrome. One mechanism that may participate in this
      association is upregulation of inflammatory pathways. We used structural equation
      modeling to assess the interrelations between childhood obesity, OSA,
      inflammation, and metabolic dysfunction. One hundred and eighty-four children
      (127 boys, mean age: 8.5 +/- 4.1 years) had height and weight measured, underwent
      overnight polysomnography and had fasting blood taken. The blood was analyzed for
      insulin, glucose, lipids, leptin, and cytokines [interferon (IFN)-gamma,
      granulocyte macrophage-colony stimulating factor, interleukin (IL)-1beta, IL-2,
      IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha]. Structural equation
      modeling (SEM) was used to evaluate associations between the outcomes of interest
      including hypoxia, arousal (related to respiratory and spontaneous), obesity,
      metabolic dysfunction, and inflammatory markers. Two cytokine factors and one
      metabolic factor were derived for the SEM. These factors provided good fit in the
      structural equation model (chi(2)/df = 2.855; comparative fit index = 0.90, root
      mean squared error of approximation = 0.10) and all factor loadings were
      significantly different from zero (P < or = 0.01). Overall, our results indicate
      that while obesity (as measured by body mass index z-score) has a major influence
      on the metabolic dysfunction associated with OSA, arousal indices, and cytokine
      markers may also influence this association. Our results support the hypothesis
      that OSA is a contributor to the mechanisms that link sleep, systemic
      inflammation and insulin resistance, and show that the interrelations may begin
      in childhood.

PMID- 18036085
TI  - Children's sleep and adjustment: the moderating role of vagal regulation.
AB  - Children's vagal tone and vagal suppression were examined as moderators of
      associations between children's sleep disruptions and adjustment problems. A
      relatively large sample (n = 167) of boys and girls who ranged in age between 8
      and 9 years participated with their parents. Sleep was examined via actigraphy in
      the child's home for seven consecutive days. Children's vagal tone was examined
      during baseline conditions, and their vagal suppression was assessed in response
      to an inter-adult argument. In comparison with children exhibiting higher levels
      of vagal tone, those with lower vagal tone were at increased risk of
      externalizing problems, depression symptoms and higher body mass index associated
      with increased sleep disruptions (i.e. lower Sleep Efficiency, increased Wake
      Minutes and fewer Sleep Minutes). Thus, lower vagal tone functioned as a
      vulnerability factor for adjustment problems in the context of sleep problems. A
      higher level of vagal suppression to the inter-adult argument functioned as a
      protective factor against externalizing behaviors otherwise associated with
      increased Wake Minutes and reduced Sleep Efficiency. Findings demonstrating the
      moderating role of vagal functioning in the context of sleep disruptions are
      novel, and highlight the importance of individual differences in children's
      physiological regulation for sleep and adjustment.

PMID- 18036086
TI  - Cyanotic breath-holding spells in children respond to adenotonsillectomy for
      sleep-disordered breathing.
AB  - Children with breath-holding (BH) spells may demonstrate sleep-disordered
      breathing (SDB) during polysomnography. We studied five young children with
      cyanotic spells retrospectively and found both SDB and a response to
      adenotonsillectomy. We therefore proceeded with a prospective investigation of
      treatment for SDB in children with comorbid cyanotic spells. Nineteen children
      with cyanotic BH spells were identified and enrolled in the prospective study.
      Parents chose either treatment or observation. Fourteen children underwent
      complete SDB evaluation and treatment trials while five selected observation only
      (control group). Sleep and sleep-surgery specialist evaluation and
      polysomnography revealed the presence of a narrow upper-airway and an abnormal
      respiratory disturbance index in all 14 children. Nasal CPAP was not successful,
      but adenotonsillectomy performed near 14 months of age eliminated SDB. BH spells
      were eliminated 1 month after surgery, while they persisted to the end of the
      study (24 months of age) in the control group. In conclusion, the presence of
      cyanotic BH should prompt investigation and polysomnography for possible SDB.
      Independent treatment of SDB may hasten resolution of BH spells in these cases.

PMID- 18036087
TI  - Long-term effects of mandibular repositioning appliances on symptoms of sleep
      apnoea.
AB  - Mandibular repositioning appliances (MRAs) reduce symptoms of obstructive sleep
      apnoea in the short term, but the long-term effects are unknown. Our objective
      was to evaluate the long-term symptomatic effects of custom-made MRAs and to
      identify the patients who will experience subjective benefits from treatment. A
      cohort of 260 consecutive patients treated with appliances for non-apnoeic
      snoring or sleep apnoea was followed up by a questionnaire and examination after
      an average of 5.4 years. The subjective effect was defined as good when
      complaints of daytime sleepiness occurred less than once a week. A total of 185
      patients (71%) responded to the questionnaires. Of the respondents, 96 reported
      frequent use, 33 reported infrequent use, 26 reported discontinued treatment and
      30 reported modified treatment. Mild cases (apnoea-hypopnoea index [AHI] < 15)
      were likelier than more severe cases to continue treatment. Patients who had used
      MRAs reported fewer complaints of sleepiness, headaches and daytime naps.
      Frequent use (P = 0.001), few night-time awakenings before start of treatment (P
      = 0.02) and effective apnoea reduction during treatment of more severe cases (P =
      0.02) correlated with a good subjective effect at long-term follow-up. Our
      conclusion is that custom-made MRAs reduce sleep apnoea symptoms in the long
      term. The mildest cases will experience the greatest long-term benefit. The
      reason is that non-apnoeic snorers and patients with a mild disease are more
      likely to continue treatment and that their long-term results with regard to
      excessive sleepiness are similar to patients with a more severe disease.

PMID- 18036088
TI  - Electroencephalographic arousals during sleep do not alter the pressor response
      to Cheyne-Stokes respiration in subjects with chronic heart failure.
AB  - This study examined the influence of electroencephalographic (EEG) arousal on the
      magnitude and morphology of the pressor response to Cheyne-Stokes respiration
      (CSR) in subjects with congestive heart failure (CHF). Thirteen subjects with
      stable CHF (left ventricular ejection fraction, 26 +/- 7%) and CSR (apnea
      hypopnea index 52 +/- 15 h(-1)) underwent overnight polysomnography with beat-to
      beat measurement of systemic arterial blood pressure (BP). CSR events were
      divided into those with or without an EEG arousal defined according to the
      criteria of the American Sleep Disorders Association. The pressor response was
      quantified in terms of the delta BP change (difference between the minimum BP
      during apnea and maximum BP during hyperpnea). Changes in the morphology of the
      pressor response were assessed by subdividing individual respiratory events into
      six periods (three during apnea: A1, A2, A3; and three during hyperpnea: H1, H2,
      H3). Considerable fluctuations in BP and heart rate (HR) were observed across the
      CSR cycle (delta mean BP 20.2 +/- 6.5 mmHg). The presence of an EEG arousal did
      not alter the amplitude of fluctuations in BP. Mean blood pressure (MBP)
      increased 21.0 +/- 7.5 mmHg with arousal versus 19.3 +/- 5.8 mmHg without arousal
      (NS). A repeated measures ANOVA showed no significant interaction between the
      presence of arousal and the proportional change in mean BP across the six
      periods, indicating that an EEG arousal had no effect on the morphology of MBP
      change during CSR [F(5,60) = 1.44, P = 0.22]. This study showed that EEG-defined
      arousal does not amplify the pressor response to CSR in CHF.

PMID- 18036089
TI  - Diagnosis of sleep-disordered breathing in patients with chronic heart failure:
      evaluation of a portable limited sleep study system.
AB  - Sleep-disordered breathing (SDB) is common in chronic heart failure (CHF),
      affects disease progression and presents a potential therapeutic target. This
      study was designed to test the hypothesis that there would be good agreement in
      diagnostic outcome between home limited sleep studies and in-laboratory
      polysomnography (PSG) in the identification of SDB in patients with CHF. We
      performed synchronous in-laboratory Embletta and PSG, and home Embletta studies,
      prospectively in 20 consecutive patients with stable symptomatic CHF (ejection
      fraction 33 +/- 12%) on optimal medical therapy. Sleep efficiency was poor at 57
      +/- 21%. Unlike synchronous in-laboratory Embletta (kappa coefficient 0.63, P <
      0.01), home Embletta showed poor agreement with PSG (kappa coefficient 0.27, P =
      0.06). Positive and negative predictive values for home Embletta in detecting SDB
      were 83% and 57% respectively. In this relatively small study, agreement in
      diagnostic outcome between home Embletta and PSG, and negative predictive value
      for the home Embletta, were poor. We explore possible explanations for this, both
      technical and situational, which should be taken into consideration when
      considering potential screening or diagnostic tools for SDB in patients with CHF.

PMID- 18036090
TI  - Post-CPAP sleepiness--a specific syndrome?
AB  - Following treatment with continuous positive airway pressure (CPAP), some
      patients with obstructive sleep apnoea (OSA) remain sleepy despite effective CPAP
      and attention to other diagnoses that can provoke sleepiness. It is unclear if
      this residual sleepiness is an irreversible result of their previous OSA and
      merits consideration for pharmacological treatment or simply because of the many
      and varied causes of sleepiness normally found in the community. We have measured
      levels of sleepiness, using the Epworth Sleepiness Score (ESS), in 572 patients
      on CPAP and compared them with a control group of 525 subjects from a community
      survey, which would have included the usual lifestyle reasons for sleepiness as
      well as any undiagnosed sleep disorders. There was no difference in the
      percentage of patients with an ESS >10 in the CPAP group compared with the
      controls (16.1 versus 14.3, P = 0.54). Thus, although there clearly are sleepy
      patients within the CPAP group, the prevalence is no higher than in the
      community. We question whether so-called 'post-CPAP sleepiness' should be
      regarded as any more abnormal and worthy of treatment than a 'normal' population.
      Post-CPAP sleepiness as a specific disorder may not exist.

PMID- 18036091
TI  - Association of Type D personality to perceived side effects and adherence in CPAP
      treated patients with OSAS.
AB  - Continuous positive airway pressure (CPAP) is the treatment of choice for
      obstructive sleep apnoea syndrome (OSAS), but side effects are common and long
      term adherence low. The Type D (distressed) personality is defined as a
      combination of negative affectivity and social inhibition. The association of
      Type D personality with adherence has not been studied in CPAP-treated patients
      with OSAS. This study aimed to describe the prevalence of Type D personality in
      OSAS patients with CPAP treatment longer than 6 months and the association with
      self-reported side effects and adherence. A cross-sectional descriptive design
      was used. A total of 247 OSAS patients with a mean use of CPAP treatment for 55
      months (6-182 months) were included. Data collection was achieved by two
      questionnaires; the Type D scale 14 (DS14) (Type D personality), SECI (side
      effects of CPAP), as well as from medical records (clinical variables and
      objective adherence to CPAP treatment). Type D personality occurred in 30% of the
      patients with OSAS and significantly (P < 0.05-0.001) increased the perceived
      frequency and severity of a broad range of side effects. The objective adherence
      was significantly lower (P < 0.001) for OSAS patients with Type D compared to
      OSAS patients without Type D, both with regard to a mean use of 4 h per night and
      85% of the self-rated sleep time per night. The additional effect of a Type D
      personality on perceived side effects and adherence to CPAP treatment found in
      this study could be used by healthcare personnel when evaluating patients waiting
      for treatment.

PMID- 18036092
TI  - Improvement in energy and vitality over a short-term CPAP trial predicts long
      term compliance in patients with obstructive sleep apnea.

PMID- 18036094
TI  - Estimation of the seed dispersal kernel from exact identification of source
      plants.
AB  - The exact identification of individual seed sources through genetic analysis of
      seed tissue of maternal origin has recently brought the full analytical potential
      of parentage analysis to the study of seed dispersal. No specific statistical
      methodology has been described so far, however, for estimation of the dispersal
      kernel function from categorical maternity assignment. In this study, we
      introduce a maximum-likelihood procedure to estimate the seed dispersal kernel
      from exact identification of seed sources. Using numerical simulations, we show
      that the proposed method, unlike other approaches, is independent of seed
      fecundity variation, yielding accurate estimates of the shape and range of the
      seed dispersal kernel under varied sampling and dispersal conditions. We also
      demonstrate how an obvious estimator of the dispersal kernel, the maximum
      likelihood fit of the observed distribution of dispersal distances to seed traps,
      can be strongly biased due to the spatial arrangement of seed traps relative to
      source plants. Finally, we illustrate the use of the proposed method with a
      previously published empirical example for the animal-dispersed tree species
      Prunus mahaleb.

PMID- 18036097
TI  - Lentivirus-mediated superoxide dismutase1 gene delivery protects against
      oxidative stress-induced liver injury in mice.
AB  - BACKGROUND: The exposure of liver to hepatotoxins, and their subsequent
      metabolism, results in increased reactive oxygen species (ROS), one of the major
      culprits in causing both acute liver cell injury and chronic liver diseases. The
      aim of this present study is to investigate the protective effects of lentiviral
      vector-mediated copper-zinc superoxide dismutase (LV-SOD1) gene transfer against
      ROS-induced cytotoxicity in Hep G2 cells and liver injury in mice. METHODS: In
      vitro SOD1 efficacy was tested against two ROS-generating systems:
      hypoxanthine/xanthine oxidase (HX/XO) and hydroxyethyl radicals (HER), whereas in
      vivo SOD1 efficacy was evaluated in carbon tetrachloride (CCl4)-induced liver
      injury in C57BL/6 mice. RESULTS: LV-SOD1 transduction in Hep G2 cells resulted in
      a significant increase in SOD activity in cell lysates, and it significantly
      decreased the toxicity induced by HX/XO and HER. High SOD1 expression in the
      liver was achieved via portal vein injection of LV-SOD1 in mice and these high
      levels were observed for 30 days, the length of the experiment to date. SOD1
      overexpression significantly decreased the toxicity and restored liver function
      in the CCl4-treated mice. CONCLUSIONS: These findings demonstrate for the first
      time that LV transduction led to the long-term expression of fully functional
      transgene expression in both in vitro and in vivo systems.

PMID- 18036096
TI  - Managing chronic hepatitis C in the difficult-to-treat patient.
AB  - Patients with chronic hepatitis C virus (HCV) infection and disease-related
      complications - among them cirrhosis and liver failure - pose a particular
      management challenge. Some of these patients may fail to respond to current
      therapy (non-responders), and some are affected so severely that treatment puts
      them at an unacceptable risk for complications. Treatment with pegylated
      interferon (peg-IFN) plus ribavirin improves hepatic enzyme levels and eradicates
      the virus in approximately 50% of patients; however, a significant number of
      patients do not respond to therapy or relapse following treatment
      discontinuation. Several viral, hepatic and patient-related factors influence
      response to IFN therapy; many of these factors cannot be modified to improve long
      term outcomes. Identifying risk factors and measuring viral load early in the
      treatment can help to predict response to IFN therapy and determine the need to
      modify or discontinue treatment. Retreatment options for patients who have failed
      therapy are limited. Retreatment with peg-IFN has been successful in some
      patients who exhibit an inadequate response to conventional IFN treatment,
      particularly those who have relapsed. Consensus IFN, another option in treatment
      resistant patients, has demonstrated efficacy in the retreatment of non
      responders and relapsers. Although the optimal duration of retreatment and the
      benefits and safety of maintenance therapy have not been determined, an extended
      duration is likely needed. This article reviews the risk factors for HCV
      treatment resistance and discusses the assessment and management of difficult-to
      treat patients.

PMID- 18036098
TI  - A surgical model of fulminant hepatic failure in rabbits.
AB  - AIM: Animal models of fulminant hepatic failure (FHF) have been developed for
      characterization of disease progression and to evaluate the effectiveness of
      liver-assist devices, some by treatment with hepatotoxic drugs, viral hepatitis
      or surgical procedures. We have developed a model in the rabbit by combining
      resection of the three anterior lobes with ligation of the pedicle of the right
      lateral lobes, resulting in liver necrosis; the remnant quadrate lobes are left
      intact. MATERIALS AND METHODS: Adult male New Zealand white rabbits (n=16) were
      used. Six animals were killed to measure the weight of the separate liver lobes.
      The others (n=10) underwent left neck central line placement to monitor
      continuous blood pressure and collect blood for laboratory analysis, and a burr
      hole on the right parietal bone to monitor the intracranial pressure (ICP). Blood
      laboratory analysis, clinical hepatic encephalopathy and ICP levels were measured
      in FHF animals (n=6). Animals (n=4) undergoing a sham operation served as
      controls. RESULTS: All FHF animals died between 12 and 26 h after liver surgery
      from FHF characterized by a progressive increase in liver enzymes, ammonia, total
      bilirubin, coagulopathy, hepatic encephalopathy and intracranial hypertension.
      Histological features of the ischaemic lobes showed coagulative necrosis of
      hepatocytes with absence of nuclei and collapse of cell plates. Brain histology
      revealed hypoxic cell damage. CONCLUSION: We have developed a simple,
      reproducible model of FHF in rabbits that has a number of features comparable
      with clinical FHF patients and is well suited for testing experimental
      bioartificial liver systems and investigating the pathogenesis of FHF.

PMID- 18036099
TI  - Changes in serum hepatitis B e antigen (HBeAg) levels associated with the
      emergence of YMDD mutants in HBeAg non-seroconverted patients during lamivudine
      therapy.
AB  - BACKGROUND: To elucidate the associations between the changing patterns of
      hepatitis B e antigen (HBeAg) levels and the emergence of tyrosine-methionine
      aspartate-aspartate (YMDD) mutants in HBeAg non-seroconverted patients undergoing
      lamivudine therapy. METHODS: This study analysed 76 HBeAg-positive naive chronic
      hepatitis B patients treated with lamivudine. The median duration of therapy was
      52 weeks. The YMDD mutants were detected in 35 patients. The changing patterns of
      HBeAg levels were categorized into three groups: Descending, Descending-Ascending
      and Fluctuation. HBeAg breakthrough was defined as progressive HBeAg decreasing
      to <10% of pretreatment levels, followed by increases exceeding 50 S/Co [the
      ratio of the sample (S) to the cut-off (Co)] above nadir levels. RESULTS: Of 76
      patients, the sensitivity and specificity for predicting YMDD mutants by the
      Descending-Ascending pattern were 66 and 100% respectively. Of 17 patients with
      YMDD mutants in the Descending-Ascending group, hepatitis B virus (HBV) DNA first
      increased, followed by increased HBeAg levels and finally by biochemical
      breakthrough. The median intervals between virological breakthrough and HBeAg
      breakthrough, between HBeAg breakthrough and biochemical breakthrough and between
      virological breakthrough and biochemical breakthrough were 4, 24 and 33 weeks
      respectively. CONCLUSIONS: Serial HBeAg levels are useful in predicting YMDD
      mutant emergence in HBeAg non-seroconverted patients during lamivudine therapy.

PMID- 18036100
TI  - Evolution of hepatitis C virus infection under host factor influence in an
      ethnically complex population.
AB  - BACKGROUND: The ethnic influence makes it difficult to reach a consensual
      definition of host-dependent genetic factors controlling the hepatitis C virus
      (HCV) disease course. AIMS: To investigate, in an ethnically complex Brazilian
      population, whether human leucocyte antigen (HLA) molecules are associated with
      susceptibility to HCV infection, self-limiting viral clearance and predisposition
      to chronic disease. METHODS: One hundred and four HCV-antibody-positive patients
      (stratified into groups with spontaneous viral clearance and chronic HCV
      infection) and 166 healthy controls were submitted to HLA genotyping. RESULTS:
      Two strong associations were observed between the susceptibility to HCV infection
      and DRB3 [odds ratio (OR), 4.03; 95% confidence interval (CI), 2.40-6.77;
      P(c)=0.0000041] and DQB1*02 (OR, 1.72; 95% CI, 1.05-2.84; P=0.041), and between
      the spontaneous viral clearance and DRB1*01 (OR, 4.59; 95% CI, 1.70-12.41;
      P=0.003) and DQB1*03 (OR, 2.83; 95% CI, 1.14-7.02; P=0.029). No evidence was
      observed regarding the epidemiology or viral genotype influence on the disease
      course. CONCLUSION: We could confirm with a highly admixed population the
      association of viral clearance with two allele groups (DRB1*01 and DQB1*03)
      previously reported in homogeneous populations. The identification of DRB1*01 and
      DQB1*03 involved with self-limiting hepatitis in different ethnic groups is a
      very important finding that will contribute to the current knowledge about HCV
      host interaction and the development of therapeutic vaccines.

PMID- 18036101
TI  - Performance of Doppler ultrasound in the prediction of severe portal hypertension
      in hepatitis C virus-related chronic liver disease.
AB  - PURPOSE: To evaluate the correlation between hepatic vein pressure gradient
      measurement and Doppler ultrasonography (DUS) in patients with chronic liver
      disease (CLD). PATIENTS AND METHODS: Sixty-six patients with fibrotic to
      cirrhotic hepatitis C virus-related CLD, were consecutively included upon
      referral to our haemodynamic laboratory. Superior mesenteric artery pulsatility
      index (SMA-PI), right interlobar renal and intraparenchymal splenic artery
      resistance indices, were determined, followed by hepatic venous pressure gradient
      (HVPG) measurement. RESULTS: A correlation was found between HVPG and
      intraparenchymal splenic artery resistance index (SA-RI) (r=0.50, P<0.0001), SMA
      PI (r=-0,48, P<0.0001), right interlobar renal artery resistance index (RRA-RI)
      (r=0.51, P<0.0001) in the whole patient population. However, dividing patients
      according to the presence/absence of severe portal hypertension (i.e. HVPG > or
      =12 mmHg), a correlation between HVPG and intraparenchymal SA-RI (r=0.70,
      P<0.0001), SMA-PI (r=-0.49, P=0.02), RRA-RI (r=0.66, P=0.0002) was observed only
      for HVPG values <12 mmHg. HVPG but not DUS correlated with the presence of
      esophageal varices (P<0.0001). CONCLUSIONS: Superior mesenteric artery
      pulsatility index, intraparenchymal splenic and right interlobar renal artery
      resistance indices do not adequately predict severe portal hypertension.

PMID- 18036102
TI  - Treatment of chronic portosystemic encephalopathy in cirrhotic patients by
      embolization of portosystemic shunts.
AB  - AIMS/BACKGROUNDS: Large spontaneous portal-systemic shunts can occasionally be
      the cause of chronic and disabling encephalopathy in cirrhotic patients. Shunt
      embolization has been proposed, however the clinical relevance of this technique
      remains uncertain. METHODS/RESULTS: We report our results in seven patients
      treated by shunt embolization. Although the procedure was achieved and
      technically successful in all patients, the clinical results were poor as long
      term improvement was obtained in only one patient. Three patients died within 3
      months after the procedure from cirrhoses' end stage complications. CONCLUSION:
      We believe that optimal management of these patients with chronic spontaneous
      encephalopathy is liver transplantation.

PMID- 18036103
TI  - The benign course of liver disease in adults with cystic fibrosis and the effect
      of ursodeoxycholic acid.
AB  - BACKGROUND AND AIMS: The life expectancy of patients with cystic fibrosis (CF)
      has been increasing and the associated liver disease has emerged as a significant
      medical issue. Our aim was to describe the clinical features, course and effect
      of ursodeoxycholic acid (UDCA) on liver disease in an adult CF population. STUDY:
      From 1983 to 2005, 278 patients with CF were followed up at the Alfred Hospital,
      an adult tertiary referral centre. Twenty-seven patients (9.7%) satisfied the
      criteria for liver disease and their clinico-pathological features were assessed.
      The effect of UDCA on hepatobiliary symptoms and biochemical parameters was
      determined. RESULTS: The mean age at liver disease diagnosis was 23 years (range
      8-47 years). Portal hypertension was present in 18 (67%) patients. During a
      median follow-up of 7 years (range 1.5-15), variceal haemorrhage occurred in two
      patients and ascites in three (one spontaneously). Nine (33%) patients died and
      five (19%) underwent lung transplantation. There was no encephalopathy, liver
      transplantation or liver-related deaths. UDCA was taken by 22 patients and was
      associated with a significant improvement in hepatobiliary symptoms [11/22 (50%)
      in the pre-UDCA period vs 1/22 (4%) in the post-UDCA period; P=0.0003] and a
      significant reduction in aspartate aminotransferase (P=0.005); alanine
      aminotransferase (P<0.001); gamma-glutamyltranspeptidase (P=0.021); and alkaline
      phosphatase (P<0.001). CONCLUSIONS: Liver disease in adults with CF is commonly
      complicated by portal hypertension, but morbidity and mortality associated with
      this in our small patient population were low. UDCA is associated with
      improvement in hepatobiliary symptoms and liver function tests.

PMID- 18036104
TI  - Efficacy of hepatitis B virus (HBV) vaccination in treating lamivudine-resistant
      HBV reactivation following hepatitis B surface antigen seroconversion.
AB  - BACKGROUND: HBsAg vaccination might help to control HBV replication following
      nucleos(t)ide analog therapy. We tested HBsAg vaccine in a patient who developed
      lamivudine resistance. PATIENT AND RESULTS: An HBeAg negative HBV chronically
      infected patient developed HBsAg seroconversion after 3 years of treatment by
      lamivudine. However, the control of HBV replication was transient and HBV DNA
      could be detected in the serum one year after lamivudine was stopped.
      Concurrently, the anti-HBs antibodies (HBsAb) titre had decreased from more than
      100 IU/L to 23 IU/L. Due to the presence of rtM204V resistance mutation,
      lamivudine was not reintroduced and the patient was treated by HBsAg vaccination.
      After three injections, HBV DNA was no more detectable and the HBsAb titre
      reached more than 200 IU/L. CONCLUSION: This observation suggests that a regular
      follow up of patients presenting HBsAg seroconversion following lamivudine
      therapy is necessary. In these patients, a low titre of HBsAb may not prevent
      from lamivudine-resistant HBV reactivation. Evaluation of HBsAg vaccination to
      maintain HBsAb at a high titre in these patients deserves further studies.

PMID- 18036105
TI  - Case of rapidly progressed sarcomatoid hepatocellular carcinoma in a young female
      without risk factor.

PMID- 18036106
TI  - Hepatocellular carcinoma with situs inversus totalis and polysplenia syndrome.

PMID- 18036107
TI  - Overseas-trained nurses, diversity and discrimination: perceptions, practice and
      policy.

PMID- 18036108
TI  - Embodiment of discrimination and overseas nurses' career progression.
AB  - AIM AND OBJECTIVES: To examine empirically and in-depth how discriminatory
      attitudes and practices are experienced by overseas nurses and how the
      discrimination may affect their well-being and career progression and,
      furthermore, to apply the theoretical perspective of embodiment in understanding
      these processes. BACKGROUND: The UK healthcare sector has, in recent years,
      relied on overseas-trained professionals to fill up vacancies in nursing and
      other professions. Research shows that overseas nurses claim that their UK
      colleagues, managers and patients express discriminatory, racist and xenophobic
      attitudes. DESIGN AND METHOD: The paper provides an existential phenomenological
      analysis of in-depth interviews with two overseas nurses. The data are drawn from
      a study of overseas-trained healthcare workers' experiences working and living in
      the UK. The two cases have been purposively selected to provide an illumination
      and discussion of personal experiences with discrimination, how individuals may
      respond to these and how their professional career is affected. FINDINGS:
      Discrimination towards migrant workers may, at times, be experienced as 'blatant
      racism' or, in more subtle forms, as 'aversive racism'. It is demonstrated how
      such discrimination may impact on the afflicted person's sense of self,
      suggesting a theoretical model of the embodiment of discrimination.
      Discrimination not only works at an interpersonal and institutional level, but is
      a form of 'symbolic violence' that may be internalized to affect the person's
      'habitus'; it can be resisted through meaning-making activity that explains and
      hence objectifies and embodies the experience in a way that allows individuals to
      positively influence their situation through agency. CONCLUSION: This article
      details how social and institutionalized discrimination in the UK healthcare
      sector may be internalized by overseas workers and affects their professional
      careers. RELEVANCE TO CLINICAL PRACTICE: The study allows a theoretical
      reflection on the damage inflicted by discrimination, and it may contribute to
      the eradication of discriminatory practices and the development of necessary
      support and monitoring mechanisms.

PMID- 18036109
TI  - Institutionalized disadvantage: older Ghanaian nurses' and midwives' reflections
      on career progression and stagnation in the NHS.
AB  - AIMS AND OBJECTIVES: This paper explores the perceptions of career progression in
      the NHS of a group of midwives and nurses trained in Ghana and working in the UK.
      It draws on semi-structured interviews with nurses, midwives and managers which
      were conducted as part of the Researching Equal Opportunities for Overseas
      trained Health Professionals project (REOH). BACKGROUND: Research into overseas
      nurses in the UK has tended to focus on their experiences of discrimination in
      relationships with colleagues, managers and patients. There is limited
      statistical evidence indicating that migrant nurses experience slower career
      progression than their UK-trained counterparts. However, there is little analysis
      of their experiences and perceptions of the process of career progression or
      their understandings of the factors that could account for their limited entry
      into higher grades. CONCLUSIONS: This paper argues that many Ghanaian nurses and
      midwives can experience difficulty in progressing into senior positions because
      of cultural differences and gaps in knowledge. However, this paper indicates that
      these problems can become institutionalized and entrenched by practices on the
      ward, particularly support from managers being dispensed as patronage that is not
      given equally to all. This creates an informal system of promotion to management
      which is not transparent, is based on subjective and culturally specific criteria
      and can undermine egalitarian formal procedures and create spaces where
      discriminatory practices can operate. RELEVANCE TO CLINICAL PRACTICE: These
      processes can lead to sectors of the workforce becoming demoralized, to the
      wastage of skills and other resources and problems in staff retention.

PMID- 18036110
TI  - The rhetoric of caring and the recruitment of overseas nurses: the social
      production of a care gap.
AB  - AIMS AND OBJECTIVES: I will argue that overseas nurse recruitment is the
      consequence of a care gap, which arose from several policy shifts in the 1990s
      and in part from the rhetoric of a normative moral discourse in the UK which
      claims that caring is the moral essence of nursing. I will suggest that this
      discourse has masked the uncoupling of caring from nursing practice and that this
      uncoupling places the overseas nurses in a contradictory position. BACKGROUND: In
      an increasingly competitive global labour market, the UK is faced with a nursing
      shortage and has been recruiting trained nurses from abroad (NMC 1993-2002).
      DESIGN AND METHODS: This paper is based on two related, qualitative studies using
      semi-structured focus groups and individual interviews. The first explored the
      experiences of overseas nurses in the UK and the second investigated the equal
      opportunities and career progression of overseas nurses in the UK. RESULTS: The
      data from these studies challenge the normative UK value that caring is at the
      heart of nursing. These data are the lens through which we see this contradiction
      explicitly played out. Overseas nurses observe that caring (as undertaken by
      health care assistants in care homes) is not nursing yet caring is being passed
      down the line as a process that marginalizes the overseas nurses and at the same
      time devalues their skills. I do not argue that overseas nurses care at a higher
      standard (although this may be the case) just that they care differently, that
      they expected UK nurses to deliver basic care and, instead, experience UK nursing
      practice as less autonomous and of a lower standard than they expected.
      CONCLUSIONS: I argue that the overseas nurses' views help us understand the
      processes by which the uncoupling of caring from nursing has come about.
      RELEVANCE TO CLINICAL PRACTICE: This paper discusses a workforce issue which is
      directly relevant to clinical practice because it focuses on the meaning of care;
      what is caring, what are caring activities and how are these represented in the
      discourse on caring in the literature? This paper also reveals significant
      worries among nursing managers about how to staff the nursing workforce and what
      nurses should be doing in the clinical areas.

PMID- 18036111
TI  - Profession, market and class: nurse migration and the remaking of division and
      disadvantage.
AB  - AIMS AND OBJECTIVES: This article aims to analyse the part played by successive
      waves of nurse migration in changing patterns of division and disadvantage within
      nursing. We argue that migration has in part acted to reinforce disadvantage
      based on class and gender, race and ethnicity and identify the influence of
      changes in nursing structure and commercialization of care in these processes.
      BACKGROUND, DESIGN AND METHODS: The historical analysis of division within
      nursing and the impact of migration are based on secondary sources (literature
      review) and primary research undertaken by ourselves and colleagues. The paper
      develops a concept of 'remaking' disadvantage drawing on analysis in social
      history of the interplay between agency and economic position in the 'making' of
      class. It uses the extended case method to focus on the residential care sector,
      showing how global and national influences operate at the frontline of service
      delivery. RESULTS: We show how social class and gender, race and ethnicity have
      interacted and are reflected in the division of labour within nursing. We
      demonstrate how the employment conditions of nurse migrants have reinforced
      patterns of disadvantage. The case study of the residential care home sector
      deepens our analysis of intersecting sources of professional disadvantage
      including aspects of commercialization, in a sector where they have severe
      effects for vulnerable staff and patients. CONCLUSIONS: In the UK, migrant
      professional nurses have repeatedly acted both as a highly valued labour force on
      whom patients and clients rely and as involuntary contributors to remaking
      disadvantage. This situation is sustained by the current international labour
      market and rising commercialization which facilitate nurse migration and the
      segmentation of care work based on a 'pecking order' of specialties that
      reinforce existing divisions of social class, gender and race within nursing.
      RELEVANCE TO CLINICAL PRACTICE: Migrant nurses play a key role in the delivery of
      'frontline' care to patients. The role many currently play reinforces
      disadvantage within nursing in ways that are problematic for the profession,
      patients and clients. The recognition and valuing of their skills is critical to
      the promotion of their own morale which in turn has an impact on their
      relationship with colleagues and the delivery of patient and client care.

PMID- 18036112
TI  - Engaging with a new reality: experiences of overseas minority ethnic nurses in
      the NHS.
AB  - AIM AND OBJECTIVE: The purpose of this study was to explore, describe and develop
      a greater understanding of the experiences of overseas black and minority ethnic
      nurses in the National Health Service (NHS) in the south of England. BACKGROUND:
      For the past five decades, the NHS has been recruiting overseas black and
      minority ethnic nurses from several former British colonies to alleviate the
      manpower shortages. More recently there has been a shortage of nurses in the
      labour force and as a result the NHS has once again recruited overseas nurses.
      Despite this recruitment drive there are limited studies outlining how overseas
      black and minority nurses have fared in the NHS. METHODS: This qualitative
      phenomenological study used four purposeful focus groups and all participants
      involved were interviewed at a place convenient for them. These all non-white
      participants originated from Asia, Africa and the Caribbean. Each focus group
      contained six participants with an overall total of 24 participants involved in
      the study. RESULTS: Following thematic analysis, the findings revealed six themes
      such as, the devaluation process, concept of self-blame, discrimination/lack of
      equal opportunity, concept of invisibility, experiencing fear and benefits of
      being here. Several overseas nurses felt devalued and indicated that white UK
      nurses appeared to have placed little trust in them. They stated that both
      discrimination and lack of equal opportunity were present in the workplace and
      they also revealed that some white UK nurses were sometimes abusive. As a result
      they tolerated such behaviour for fear of being thrown out with their families.
      Despite such negative experiences participants indicated that the experiences
      gained whilst working in the NHS were useful. CONCLUSIONS: There is a need for
      overseas nurses to be treated fairly and with respect particularly in the light
      of an acute labour shortage of nurses in the NHS. The findings suggest that
      overseas minority ethnic nurses' experiences have been mixed, with some positive
      as well as negative experiences, within a process that devalues them as workers.
      RELEVANCE TO CLINICAL PRACTICE: This paper highlights a need for a re-evaluation
      of equal opportunity policies and proposes more diversity training so as to
      prepare nurses to cope with an increasingly complex and diverse workforce.

PMID- 18036113
TI  - Overseas nurses in the National Health Service: a process of deskilling.
AB  - AIMS AND OBJECTIVES: This paper shows that overseas nurses (OSN) recruited to UK
      hospital trusts become deskilled in technical aspects of clinical practice.
      BACKGROUND: Existing research reports that many newly recruited OSN are prevented
      from using technical skills acquired in training abroad, to the detriment of the
      National Health Service (NHS) and the concern of the nurses themselves. DESIGN:
      The author conducted case study work in three NHS hospital trusts in the
      northwest of England. The findings reported are part of a wider investigation
      into the assimilation(1) of OSN from the Philippines, India and Spain into NHS
      hospitals. Semi-structured interviews were undertaken with members of four groups
      of actors: managers, OSN, home nurses (HN) and mentors, which were analysed
      thematically. Results. The research confirms the finding that many OSN are
      prevented from using technical skills in the UK, but also suggests reasons why
      this is so. The finding of deskilling emerged strongly in all three cases and is
      singled out for discussion in this paper. CONCLUSIONS: The experience of OSN
      highlights ambiguity surrounding the role of the nurse in British hospitals. This
      arises partly because OSN tend to be recruited to the bottom grades of nursing in
      the NHS, where their technical skills are underused. RELEVANCE TO CLINICAL
      PRACTICE: Segmentation within the nursing hierarchy contributes to the
      conflicting messages and mismatch of expectations experienced by nurses at the
      ward level, regarding the role of the nurse.

PMID- 18036114
TI  - Contexts, motives and experiences of Nigerian overseas nurses: understanding
      links to globalization.
AB  - AIMS: Current understanding of the perspectives and experience of overseas
      trained nurses working in the UK and how these relate to conditions of
      globalization, is limited. This article (i) presents evidence on the contexts,
      circumstances and perspectives of Nigerian trained nurses working in the UK and
      (ii) examines their relationships to globalization by building on prior analyses
      that use Bauman's concepts of 'global' and 'local' perspectives. METHODS: The
      evidence derives from an exploratory qualitative investigation in the UK and
      Nigeria among a small sample of Nigerian trained registered nurses working in the
      independent nursing home sector in England (n = 25) and registered nurses,
      nursing tutors and returnee migrants in Nigeria (n = 7). FINDINGS: Nurses'
      migration motives arise from a deterioration in their economic, work and status
      situation over the past two decades in the context of a macro-economic decline in
      Nigeria. Their decisive motivation is to gain financially with a view to
      achieving certain material standards and prospects for self and children in
      Nigeria. Contrary to their expectations, they experience a loss in professional
      and social status in the UK. CONCLUSION: In their de facto'global' migration,
      principally for economic reasons, Nigerian nurses hold a decidedly 'local'
      normative perspective. This is reinforced by their experiences of work tensions,
      which reflect the globalization of biographies. RELEVANCE TO CLINICAL PRACTICE:
      Further evidence such as that provided, on the contexts and perspectives of
      overseas nurses, as also of UK staff, will enable the appropriate management of
      developing world-UK nursing migration and its host system implications.

PMID- 18036115
TI  - Interrogating the language of integration: the case of internationally recruited
      nurses.
AB  - AIMS: This paper suggested the need to interrogate the notion of 'integration' to
      facilitate the retention of migrant nurses. BACKGROUND: The growth in
      internationally recruited nurses in the UK's health system has led to a raft of
      policies that aim to ensure that such nurses are well 'integrated' into their
      'new environment'. It is assumed that integration will improve the quality of
      internationally recruited nurses' experience in the UK, improve their retention
      rates and thus improve the quality of health delivery within the UK. However,
      most of the steps through which integration is sought tend to move between some
      version of assimilation and 'respect for difference'. CONTRIBUTIONS: This paper
      aimed to add to existing literature on the integration of internationally
      recruited nurses in the UK by suggesting three steps towards rethinking
      'integration policies'. It suggests the need to recognize migration as only one
      of the differentiating factors within the nursing sector, to ensure that
      integration does actually become a two-way process and to be cognizant of the
      multiple shapes that racism can take. The first two steps will prevent a slip
      between integration and assimilation while the last will help rethink any anti
      racist training that may form part of integration policies. CONCLUSIONS: There
      are many factors influencing the experiences of internationally recruited nurses
      and not all of them can be addressed within current integration policies.
      RELEVANCE TO CLINICAL PRACTICE: Rethinking integration can help improve the
      experience of internationally recruited nurses.

PMID- 18036116
TI  - Managing equality and cultural diversity in the health workforce.
AB  - AIMS: This article offers practical strategies to managers and others for
      supporting overseas trained nurses and managing cultural diversity in the health
      workforce. BACKGROUND: Widespread nursing shortages have led managers to recruit
      nurses from overseas, mainly from developing countries. This paper draws on
      evidence from the Researching Equal Opportunities for Internationally Recruited
      Nurses and Other Health Professionals study reported elsewhere in this issue,
      which indicates that overseas trained nurses encountered widespread
      discriminatory practices including an overuse of complaints and grievances
      against them. The researchers also found that the overseas trained nurses
      responded to their experiences by using various personal strategies to resist or
      re-negotiate and overcome such discriminatory practices. METHODS: A research
      workshop was held in June 2005 at the midpoint of the Researching Equal
      Opportunities for Internationally Recruited Nurses and Other Health Professionals
      study. Twenty-five participants attended the workshop. They were the Researching
      Equal Opportunities for Internationally Recruited Nurses and Other Health
      Professionals study researchers, advisory group members, including the author of
      this paper and other researchers in the field of migration. The overall aim of
      the workshop was to share emerging research data from the Researching Equal
      Opportunities for Internationally Recruited Nurses and Other Health Professionals
      and related studies. The final session of the workshop on which this paper is
      based, was facilitated by the author, with the specific aim of asking the
      participants to discuss and determine the challenges to managers when managing a
      culturally diverse workforce. The discussion yielded four main themes collated by
      the author from which a framework of strategies to facilitate equality and
      cultural diversity management of the healthcare workers may be developed. The
      four themes are: assumptions and expectations; education and training to include
      cultural sensitivity, equality and human rights; performance management; and
      transparent human resource management processes. CONCLUSION: Managing a racially
      and culturally diverse workforce is complex and challenging for managers. There
      are no ready-made tools to show them how to do so. Achieving effective management
      of a culturally diverse workforce comes from an intrinsic motivation to develop
      the cultural competence to engage with them. IMPLICATIONS FOR PRACTICE: This
      article, together with others in this special issue, provides a springboard for
      moving this agenda on. It offers managers a framework of themes, which they can
      draw on to develop their own best practice for managing racial equality and
      cultural diversity in the health workforce.

PMID- 18036117
TI  - Academics' perceptions of the professional or clinical doctorate: findings of a
      national survey.
AB  - AIMS AND OBJECTIVES: The aim of this study was to report the perceptions of
      senior academics' working in institutions of higher education towards
      professional doctorates for the health and social care professions. BACKGROUND:
      The professional doctorate is a product of its time introduced for the purpose of
      developing and improving clinical practice. The extent to which this has been
      realised, however, has yet to be determined, there being little empirical or
      theoretical work in this field. This research is an attempt to begin to produce
      an evidence base in this area by reporting the views of those stakeholders
      responsible for delivering the curriculum and its intended aim of improving
      clinical practice. DESIGN: A modified version of illuminative evaluation was
      designed to map the range of perceptions and intended outcomes of the
      professional doctorate. METHODS: Fifty-five academics from 41 institutions of
      higher education were telephone interviewed and their perceptions of the
      professional doctorate elicited, together with a content analysis of the
      curriculum documents. RESULTS: Academics' views fell into one of three broad
      categories: enthusiastic, ambivalent and sceptical. CONCLUSIONS AND RELEVANCE TO
      PRACTICE: Academics' perceptions of the professional doctorate may have a bearing
      on whether the stated aim of the curriculum and improvements in clinical practice
      is realised. Academics are responsible for the recruitment of students and the
      quality of the educational experience. Respondents' perceptions raise questions
      about their commitment to professional doctorates relative to PhD, factors that
      will be considered during stages two and three of this research where the views
      of students and sponsors will be reported.

PMID- 18036118
TI  - The training needs of health care support workers: results of a study of workers
      and their managers.
AB  - AIMS AND OBJECTIVES: This study was designed to assess the training needs of
      health care support workers. In the past, opinions on the topic have been varied,
      but were rarely based on empirical evidence. DESIGN AND METHODS: The study was
      designed as a self-report questionnaire survey of health care support workers and
      their managers in six units in health and social care, using as its basis 32
      descriptors from the NHS Knowledge and Skills Framework, levels 1 and 2. The
      achieved sample was 117, giving a 77% response rate. RESULTS: Thirty-five per
      cent of respondents thought that health care support workers were 'unable' to
      perform six or more of the 32 descriptors used, whilst on the criterion of being
      'less than able', the figure was 64%. Support workers and their managers agreed
      closely (rho = 0.8) on where the difficulties lay in achieving Knowledge and
      Skills Framework competencies. Those difficulties lay particularly in two areas:
      (1) biomedical/physiological knowledge and (2) data-handling. CONCLUSIONS: We
      concluded that the numbers in need of training were substantial and the areas of
      need were the two identified above. RELEVANCE TO CLINICAL PRACTICE: The main
      implications for clinical practice are that (a) for those who supervise or mentor
      health care support workers, there should be a greater concentration on the more
      scientific areas of expertise and (b) a similar emphasis is needed for those who
      train mentors or supervisors. These implications will become more important over
      time as scientific knowledge about medicine and health care increases.

PMID- 18036119
TI  - An exploratory study of web-enhanced learning in undergraduate nurse education.
AB  - AIM: The aim of the study was to explore undergraduate nursing students' views of
      web-enhanced learning and to examine issues relating to their pattern of access
      to a rehabilitation nursing module website. BACKGROUND: As information technology
      is an integral component of western health care, all nurses are expected to have
      the necessary knowledge, skills and attitudes to be competent in its use.
      METHODS: In phase 1, a focus group interview was conducted with students (n = 6)
      who had not logged onto a similar module website. In phase 2, a questionnaire was
      administered to students undertaking the web-enhanced module. In phase 3, each
      student's (n = 231) pattern of access to the module was identified and compared
      with the student's performance as evidenced by their module assignment mark.
      RESULTS: Students held favourable attitudes towards web-enhanced learning but
      some students experienced difficulties. There was a significant positive
      association between the students' assignment mark and the number of times logged
      onto the module website. Significant negative correlations were found between
      mark and week of first log on, and week of first log on and number of hits onto
      the module site. This suggests that students who logged onto the module in the
      first few weeks were more likely to achieve higher marks. CONCLUSIONS: This
      study's findings suggest that students who accessed the module website early and
      often were more likely to produce more comprehensive nursing assessments and
      consequently achieve higher assignment marks than their colleagues. RELEVANCE TO
      CLINICAL PRACTICE: The findings have relevance to all nurses as lifelong learning
      is a mandatory requirement for maintaining clinical competence and electronic
      learning can provide students (regardless of registration status) with the
      flexibility to gain access to course content at a time and place convenient to
      them. The role of electronic learning in promoting a more holistic nursing
      assessment is also discussed.

PMID- 18036120
TI  - Putting practice into teaching: an exploratory study of nursing undergraduates'
      interpersonal skills and the effects of using empirical data as a teaching and
      learning resource.
AB  - AIM: To understand student nurse-patient interaction better and to assess the
      effectiveness of a teaching and learning resource consisting of tapes and
      transcriptions of actual nurse-patient interaction. DESIGN: Applied conversation
      analysis and analysis of semi-structured lecture evaluation forms. BACKGROUND:
      Little research discusses interpersonal skills (IPS) of student-nurses, even
      though policy initiatives and literature internationally promote patient-centred
      communication as being an indicator of high-quality healthcare. Literature also
      suggests that nursing education is often far removed from the realities which
      students experience during clinical practice. METHODS: Phase 1 of the study saw
      10 student nurse-patient interactions audio recorded and transcribed and the data
      subjected to conversation analysis. Phase 2 saw tapes and transcripts of similar
      interactions used as a teaching resource with the same cohort of students (n =
      48), student evaluations of the lecture were quantitatively and qualitatively
      analysed. RESULTS: Phase 1 demonstrated that, in variance to 'best-practice'
      recommendations, student nurse-patient interactions were task-centred and
      bureaucratically organized. In phase 2, after listening to and reading a
      transcript of similar interaction, students were able to identify the limitations
      of undertaking such an approach with patients, strongly suggesting that classroom
      based knowledge is not always easily transferred into clinical practice. This
      teaching approach was positively evaluated, with written evaluations emphasizing
      the effectiveness of bringing the realities of clinical practice into the
      classroom. CONCLUSION: This study suggests that students have difficulty in
      transferring the principles of 'good' communication from the classroom into their
      own interactions with patients. Students' written and spoken evaluations were
      reminiscent of the previous work performed in discussing the concept of a 'hidden
      curriculum' in professional training. RELEVANCE TO CLINICAL PRACTICE: The use of
      empirical data in the practice of IPS teaching is recommended as a means of
      closing the theory-practice gap. Student nurses and mentors need to consider the
      effect of the hidden curriculum on their IPS.

PMID- 18036121
TI  - The quality of written information for parents regarding the management of a
      febrile convulsion: a randomized controlled trial.
AB  - AIMS AND OBJECTIVES: To identify whether providing a new information leaflet for
      parents regarding the management of a febrile convulsion was more effective in
      comparison with standard leaflets. BACKGROUND: Although information leaflets are
      frequently recommended within healthcare, their quality is often poor.
      Furthermore, the evidence regarding the effectiveness of leaflets is
      inconsistent. Few studies have evaluated the effects of providing leaflets that
      have been developed to improve their quality. Within the specialty of
      paediatrics, parents are often unprepared regarding the management of febrile
      convulsion at home and the provision of supplementary leaflets is recommended,
      despite limited evidence regarding the effectiveness of this approach. There is
      also limited evidence regarding whether improving the quality of these leaflets
      leads to better outcomes, e.g. increasing parents' behavioural knowledge. DESIGN:
      Double-blind randomized controlled trial. METHOD: One hundred and twenty-six
      parents of children hospitalized due to benign febrile convulsion were recruited
      (May 2000-February 2002). Seventy-one parents were randomized to receive the
      standard care (control leaflet) and 55 parents received the intervention (new
      leaflet). Data were collected from parents on discharge immediately prior to
      receiving the intervention and 7-14 days following the intervention via telephone
      interview. RESULTS: Parents who received the new leaflet found this to be more
      reassuring and easier to understand than parents who received the control
      leaflet. No differences between groups were identified regarding the primary
      outcome, i.e. behavioural knowledge and most of the secondary outcomes, e.g.
      perceived confidence, state anxiety and satisfaction with the leaflet.
      CONCLUSION: Although this study provides modest support for the effectiveness of
      providing high-quality leaflets, further research is required to determine the
      best methods for optimizing the effectiveness of leaflets provided at hospital
      discharge. RELEVANCE TO CLINICAL PRACTICE: The quality of leaflets may influence
      some outcomes, e.g. understanding and reassurance with the written information
      provided; however, additional strategies to inform parents may be necessary.

PMID- 18036122
TI  - Maternal experiences making a decision about heart surgery for their young
      children with congenital heart disease.
AB  - AIM: The aim of this study was to investigate the essence of the experience of
      mothers during the decision-making process when facing their less than three-year
      old child undergoing heart surgery due to congenital heart disease (CHD).
      METHODS: In this phenomenological study in Taiwan nine mothers were interviewed
      in their homes. They were invited to share their experience of family
      interactions and relationships while facing a decision about their child's heart
      surgery. The interviews were recorded and transcribed for further analysis
      according to Colaizzi's phenomenological methodology. RESULTS: The essence of the
      maternal experience themes during the decision-making process included (i)
      understanding the surgery step by step, (ii) role pressure, (iii) constructing
      care-taking ability, (iv) endeavouring to maintain family functioning while
      preparing for surgery and (v) deliberate consideration to make the correct
      decision. CONCLUSIONS: When parents face their child having CHD and plan heart
      surgery, the whole family is living through a stressful decision-making process.
      According to the results of this study, it is obvious that the caregivers and
      their whole families experience psychological distress, role reorganization and
      remodelling of family functioning. RELEVANCE TO CLINICAL PRACTICE: The results of
      this study provide evidence-based essential knowledge that will assist the
      management of such decision-making processes and help to prepare the child and
      the family to have confidence in the heart surgery.

PMID- 18036123
TI  - Parents' and nurses' attitudes to family-centred care: an Irish perspective.
AB  - AIMS AND OBJECTIVES: To examine the attitudes of parents and nurses to the model
      of care delivery on an in-patient children's unit in a regional general hospital.
      BACKGROUND: A review of the literature uncovered research studies relevant to the
      area under investigation, in addition to many discussion articles. METHOD: This
      descriptive survey of parents' and nurses' attitudes regarding the implementation
      and practice of a partnership approach to care was undertaken in 2003 on a
      children's unit in an Irish regional general hospital. The survey consisted of a
      self-designed questionnaire, which was posted to the sample. The scoring system
      for the questionnaire format was analysed using Statistical Package for Social
      Sciences (version 11.0). The sample consisted of parents (n = 100) and nursing
      staff (n = 44) from the children's unit. RESULTS: the findings did not suggest
      major differences between the attitudes of the two groups on the care delivery on
      the unit. The outcomes of the study showed that, while both parents and nurses
      viewed family-centred care as appropriate, there were differences between what
      parents and nurses saw as their roles on the unit. Both groups acknowledged the
      overall philosophy of care and commented on the actual application of a family
      centred, partnership approach to care in practice on the unit. CONCLUSIONS: Both
      groups agreed that there was a need for improvement of the facilities for
      resident parents on the unit. RELEVANCE TO CLINICAL PRACTICE: The findings of the
      research could act as a catalyst for change and development of the service and
      service providers. It is hoped that it will also contribute to the improved
      satisfaction of the service provided to sick children and their families by
      parents and by the nurses who provide the care.

PMID- 18036124
TI  - The perceptions of Taiwanese families who have children with learning disability.
AB  - AIMS AND OBJECTIVES: To explore the perceptions of families in Taiwan of living
      with a child who have learning disability and the parents perspectives on the
      cultural influences on their spiritual experiences. BACKGROUND: Traditionally,
      the family is the most important unit of society, family functioning is a key
      field of interest among helping professionals who provide family interventions.
      DESIGN: This study adopted qualitative research with semi-structured interviews.
      The study analysis used content analysis which was a process of identifying,
      coding and categorizing the themes in the data. METHODS: Semi-structured
      interviews were conducted with 117 parents in their homes and were interpreted by
      using content analysis to extract key conceptual themes from the transcribed
      interview texts. RESULTS: The findings revealed that the perceptions of families
      with learning disability children were wide-ranging. The stressors did not occur
      in a fixed order, they were different in degree and importance from one family to
      another. CONCLUSIONS: The results showed that the experience of analysing
      qualitative data was extremely valuable for parents in that it aided their own
      understanding of the real-life experiences of the parents and in coming to know
      the parents in a richer, more meaningful way. In doing so, nurses need to be
      aware of their own thoughts and environment without letting it influence others.
      RELEVANCE TO CLINICAL PRACTICE: The nurse should demonstrate knowledge and
      understanding of the family's culture and be able to show respect for cultural
      difference to assess and identify culturally acceptable health-care
      interventions.

PMID- 18036125
TI  - The experiences of Chinese family members of terminally ill patients - a
      qualitative study.
AB  - AIM: To describe and understand the experiences of Chinese family members of
      terminally ill patients during the end of life process in a palliative care unit.
      BACKGROUND: Palliative care aims to provide care to dying patients and their
      family members. Skillful interventions are necessary to help family members cope
      with the impending death of the patient and maintain their emotional equilibrium.
      Hence, it is important to understand the experiences of family members of
      palliative care. DESIGN: A phenomenological study was conducted. Data were
      collected by semi-structured interviews. We interviewed a purposive sample of 20
      family members of terminally ill patients in a palliative care unit in Hong Kong.
      The data were analysed following Colaizzi's phenomenological methodology.
      RESULTS: Family members experienced anticipatory grief, with reactions that
      included anger, unease, sadness and helplessness. This was particularly acute
      when the patient was first admitted to the palliative care unit. However, the
      family members quickly accepted the reality and committed themselves to the care
      of the patient, seeking informational and emotional support from the nurses. The
      families wanted to be assured that the patient had been offered good care and
      suffered no pain. It was considered important to be with the patient during the
      dying process. CONCLUSION: This study demonstrated that Chinese family members
      were committed to the care of the patients in the palliative care unit. Cultural
      beliefs played a part in influencing family emotions and concerns. RELEVANCE TO
      CLINICAL PRACTICE: This study offers a direction for family interventions that
      acknowledge the reactions of family members to the admission of a patient to a
      palliative care unit. It highlights that families need active informational and
      emotional support from nurses.

PMID- 18036126
TI  - Commentary on Hov R, Hedelin B & Athlin E (2007) Being an intensive care nurse
      related to questions of withholding or withdrawing curative treatment. Journal of
      Clinical Nursing 16, 203-211.

PMID- 18036128
TI  - Commentary on Hsu L-L (2006) An analysis of clinical teacher behaviour in a
      nursing practicum in Taiwan. Journal of Clinical Nursing 15, 619-628.

PMID- 18036129
TI  - Commentary on Kendall S (2006) Being asked not to tell: nurses' experiences of
      caring for cancer patients not told their diagnosis. Journal of Clinical Nursing
      15, 1149-1157.

PMID- 18036131
TI  - Relationship of highly sensitive C-reactive protein and lipid levels in
      adolescents with type 1 diabetes mellitus.
AB  - BACKGROUND: Atherosclerosis appears to begin in youth with type 1 diabetes
      mellitus (T1DM). Highly sensitive C-reactive protein (hsCRP) is an independent
      marker of cardiovascular disease (CVD) risk in adults, but its relation to
      dyslipidemia and other CVD risk factors in adolescents with T1DM is unknown.
      OBJECTIVE: To study the association between lipids and hsCRP in youth with T1DM.
      DESIGN: Cross-sectional cohort. METHODS: hsCRP and fasting lipids were measured
      in 74 patients with T1DM, mean age 16.2 +/- 2.62 yr, mean duration of diabetes
      7.3 +/- 4.0 yr, and mean hemoglobin A1c (HbA1c) 8.5 +/- 1.3%. According to the
      American Heart Association/Centers for Disease Control recommendations, hsCRP
      values were divided into three groups: group 1: <1.0 mg/L, low CVD risk; group 2:
      1.0-3.0 mg/L, average CVD risk; and group 3: >3 mg/L, high CVD risk. Univariate
      linear regression between hsCRP and lipid and clinical parameters was used, with
      adjustment for age. RESULTS: hsCRP was significantly associated with
      triglycerides (Tg), apoB, systolic blood pressure (SBP), and diastolic blood
      pressure (DBP). Subjects in the high CVD risk group had no further worsening of
      lipids or BP, except for a higher Tg level. ApoB, SBP, and DBP were elevated in
      females with hsCRP > or =1 compared with the low-risk group, and high-density
      lipoprotein was decreased. In males, this difference was only significant for
      SBP. CONCLUSIONS: Elevation of hsCRP to a level > or =1.0 mg/L appears to be
      associated with elevated lipid levels in adolescents with T1DM, particularly in
      females. hsCRP is a marker in youth that clusters with dyslipidemia and may
      indicate an increased CVD risk in youth with T1DM.

PMID- 18036132
TI  - Parental country of birth is a major determinant of childhood type 1 diabetes in
      Sweden.
AB  - OBJECTIVE: To test the hypothesis that the risk of childhood diabetes type 1
      increases with migration from a low to a high incidence region. METHODS: Register
      study of a national cohort of 783 547 children born between 1987 and 1993 who
      remained in Sweden in 2002, including 3225 children with childhood type 1
      diabetes identified in hospital discharge data. Logistic regression analysis was
      used to test the hypotheses. RESULTS: Offspring of two parents born in very low
      (Asia excluding Middle East and Latin America) and low (southern and eastern
      Europe and the Middle East) incidence regions had the lowest adjusted odds ratios
      (ORs) of childhood type 1 diabetes; 0.21 (0.11-0.41) and 0.37 (0.29-0.48),
      respectively, compared with the Swedish majority population. When one parent was
      born in a low incidence country and one parent was Swedish born, the adjusted ORs
      increased but remained lower than the Swedish majority population. CONCLUSIONS:
      Parental country of birth is an important determinant of childhood type 1 in
      Sweden. Heritable factors seem most likely to explain this pattern.

PMID- 18036133
TI  - Seasonality of month of birth differs between type 1 diabetes patients with
      pronounced beta-cell autoimmunity and individuals with lesser or no beta-cell
      autoimmunity.
AB  - OBJECTIVE: To establish whether children with type 1 diabetes mellitus (T1D) with
      signs of pronounced beta-cell-specific autoimmunity as reflected by high
      autoantibody titers or positivity for several beta-cell-specific autoantibodies
      show a different pattern of month of birth (MOB) compared with children with T1D
      and low beta-cell autoimmunity and that of the general population. RESEARCH
      DESIGN AND METHODS: Cosinor analysis was used to analyze MOB rhythmicity in
      Swedish children with new onset T1D (n = 572), in whom the glutamate
      decarboxylase autoantibody (GAD65Ab) titer was determined and compared with that
      in 833 healthy children, and in 505 children with T1D in Berlin, in whom the
      titers of autoantibodies to insulin, GAD65, and islet antigen-2 were compared
      with the MOB pattern in the general population (n = 446 571). RESULTS: In both
      cohorts of children with T1D, we found that children with either a high GAD65Ab
      titer (above the 80th percentile) or positivity for three beta-cell-specific
      autoantibodies differed in their pattern of MOB from the healthy population.
      CONCLUSIONS: Our past and present observations support the hypothesis that the
      autoimmune process leading to childhood T1D is in part triggered in the perinatal
      period by viral infections in genetically susceptible individuals. The present
      study suggests that the process is linked to titer levels of autoantibodies.

PMID- 18036134
TI  - Childhood obesity complicating the differential diagnosis of maturity-onset
      diabetes of the young and type 2 diabetes.
AB  - OBJECTIVE: To describe a proband with features of type 2 diabetes who was found
      to have concomitant maturity-onset diabetes of the young (MODY) and the
      consequent multigeneration genetic analysis. DESIGN: Familial genetic analysis.
      SETTING: Tertiary university medical center. PARTICIPANTS: The proband was a 13.5
      yr-old boy with marked non-ketotic hyperglycemia, obesity, systolic hypertension,
      and insulin resistance. His mother, maternal aunt, grandmother, and great
      grandmother had diabetes; his father was obese and had early ischemic heart
      disease. INTERVENTIONS: Clinical examination, laboratory work-up, and DNA study.
      OUTCOME MEASURES: Mutation in hepatocyte nuclear factor-1alpha gene, the most
      common cause of MODY. RESULTS: The proband showed elevated C-peptide level and
      was negative for beta-cell antibodies. On genetic analysis for MODY, the
      291fsinsC mutation was identified in all affected family members. A younger
      sister who was obese but had no signs of impaired glucose tolerance was also
      tested on the basis of these findings and was found to have the same mutation.
      CONCLUSIONS: The patient, who presented with apparent type 2 diabetes, had
      concomitant MODY 3, inherited from his mother's side, and some features of type 2
      diabetes secondary to marked obesity. This combination probably caused an earlier
      and more severe presentation of the disease and had significant implications for
      medical management. A search for MODY mutations should be considered in patients
      with a history of diabetes in three generations of one side of the family, even
      those in whom the clinical picture resembles type 2 diabetes.

PMID- 18036135
TI  - Prevalence of metabolic markers of insulin resistance in offspring of gestational
      diabetes pregnancies.
AB  - In utero hyperglycemia has been associated with insulin resistance (IR) in
      children; however, there are limited data in low-risk populations. The purpose of
      this study was to describe the prevalence of metabolic markers of IR in a
      primarily Caucasian cohort of gestational diabetes mellitus (GDM) offspring aged
      7-11 yr (mean 9.1) and to correlate offspring with maternal indexes. Sixty-eight
      children were recruited through a follow-up study of women who participated in a
      randomized controlled trial of minimal intervention vs. tight glycemic control
      for GDM. All participants had a fasting plasma glucose (FPG), insulin, total
      cholesterol, high-density lipoprotein cholesterol (HDL-chol), triglyceride (TG)
      level, and a 2-h oral glucose tolerance test. We calculated homeostasis model
      assessment (HOMA) and recorded body mass index and waist circumference (WC).
      Criteria for metabolic syndrome for children included: FPG > 6.0 mmol/L, HDL-chol
      < 1.03 mmol/L, TG > 1.24 mmol/L, WC > 90% for age and gender, and 2-h glucose >
      7.8 mmol/L. Among these children, 45 (66%), 17 (25%), 5 (7%), and 1 (1.5%) had
      zero, one, two, or three metabolic markers of IR, respectively.
      Hypertriglyceridemia (21%) was most prevalent, with no child having an elevated
      FPG. WC (p = 0.018) and TG (p = 0.005) were strong predictors of IR in the
      offspring after adjustment for age, gender, birthweight, family history, and
      maternal IR. Maternal and offspring HDL-chol, TG, WC, and HOMA but not fasting or
      2-h glucose levels were significantly correlated. We conclude that metabolic
      markers of IR in children exposed to GDM may be present in the absence of
      abnormal fasting or 2-h glucose values. Screening strategies that focus on
      glucose levels may need to be reconsidered to institute early intervention with
      lifestyle changes for children at risk.

PMID- 18036136
TI  - Swallowing dysfunction in Wilson's disease: a scintigraphic study.
AB  - Although dysphagia is a common complaint of patients with Wilson's disease (WD)
      and pneumonia is an important cause of death in these patients, swallowing
      function remains an underinvestigated field in this condition. The aim of this
      study was to characterize swallowing dynamics in WD patients. Eight WD patients
      and 15 age-matched controls underwent scintigraphic evaluation of oral and
      pharyngeal deglutition. Patients had significantly slower oral transit (P =
      0.008) and a greater percentage of oral residue (P = 0.006) when compared to
      controls. Two of eight patients were free of neurological symptoms at time of
      examination. Impaired oropharyngeal function was found in patients without
      dysphagia and without neurological symptoms. Our findings indicate that WD may
      present with objective swallowing dysfunction, even in the absence of
      neurological manifestations. Further studies are necessary to investigate the
      impact of this dysfunction on morbidity and mortality in WD.

PMID- 18036137
TI  - The Gup1 homologue of Trypanosoma brucei is a GPI glycosylphosphatidylinositol
      remodelase.
AB  - Glycosylphosphatidylinositol (GPI) lipids of Trypanosoma brucei undergo lipid
      remodelling, whereby longer fatty acids on the glycerol are replaced by myristate
      (C14:0). A similar process occurs on GPI proteins of Saccharomyces cerevisiae
      where Per1p first deacylates, Gup1p subsequently reacylates the anchor lipid,
      thus replacing a shorter fatty acid by C26:0. Heterologous expression of the GUP1
      homologue of T. brucei in gup1Delta yeast cells partially normalizes the
      gup1Delta phenotype and restores the transfer of labelled fatty acids from
      Coenzyme A to lyso-GPI proteins in a newly developed microsomal assay. In this
      assay, the Gup1p from T. brucei (tbGup1p) strongly prefers C14:0 and C12:0 over
      C16:0 and C18:0, whereas yeast Gup1p strongly prefers C16:0 and C18:0. This acyl
      specificity of tbGup1p closely matches the reported specificity of the
      reacylation of free lyso-GPI lipids in microsomes of T. brucei. Depletion of
      tbGup1p in trypanosomes by RNAi drastically reduces the rate of myristate
      incorporation into the sn-2 position of lyso-GPI lipids. Thus, tbGup1p is
      involved in the addition of myristate to sn-2 during GPI remodelling in T. brucei
      and can account for the fatty acid specificity of this process. tbGup1p can act
      on GPI proteins as well as on GPI lipids.

PMID- 18036138
TI  - The disulphide isomerase DsbC cooperates with the oxidase DsbA in a DsbD
      independent manner.
AB  - In Escherichia coli, DsbA introduces disulphide bonds into secreted proteins.
      DsbA is recycled by DsbB, which generates disulphides from quinone reduction.
      DsbA is not known to have any proofreading activity and can form incorrect
      disulphides in proteins with multiple cysteines. These incorrect disulphides are
      thought to be corrected by a protein disulphide isomerase, DsbC, which is kept in
      the reduced and active configuration by DsbD. The DsbC/DsbD isomerization pathway
      is considered to be isolated from the DsbA/DsbB pathway. We show that the DsbC
      and DsbA pathways are more intimately connected than previously thought. dsbA(
      )dsbC(-) mutants have a number of phenotypes not exhibited by either dsbA(-),
      dsbC(-) or dsbA(-)dsbD(-) mutations: they exhibit an increased permeability of
      the outer membrane, are resistant to the lambdoid phage Phi80, and are unable to
      assemble the maltoporin LamB. Using differential two-dimensional liquid
      chromatographic tandem mass spectrometry/mass spectrometry analysis, we estimated
      the abundance of about 130 secreted proteins in various dsb(-) strains. dsbA(
      )dsbC(-) mutants exhibit unique changes at the protein level that are not
      exhibited by dsbA(-)dsbD(-) mutants. Our data indicate that DsbC can assist DsbA
      in a DsbD-independent manner to oxidatively fold envelope proteins. The view that
      DsbC's function is limited to the disulphide isomerization pathway should
      therefore be reinterpreted.

PMID- 18036139
TI  - LeuX tRNA-dependent and -independent mechanisms of Escherichia coli pathogenesis
      in acute cystitis.
AB  - Uropathogenic Escherichia coli (UPEC) contain multiple horizontally acquired
      pathogenicity-associated islands (PAI) implicated in the pathogenesis of urinary
      tract infection. In a murine model of cystitis, type 1 pili-mediated bladder
      epithelial invasion and intracellular proliferation are key events associated
      with UPEC virulence. In this study, we examined the mechanisms by which a
      conserved PAI contributes to UPEC pathogenesis in acute cystitis. In the human
      UPEC strain UTI89, spontaneous excision of PAI II(UTI89) disrupts the adjacent
      leuX tRNA locus. Loss of wild-type leuX-encoded tRNA(5)(Leu) significantly
      delayed, but did not eliminate, FimB recombinase-mediated phase variation of type
      1 pili. FimX, an additional FimB-like, leuX-independent recombinase, was also
      found to mediate type 1 pili phase variation. However, whereas FimX activity is
      relatively slow in vitro, it is rapid in vivo as a non-piliated strain lacking
      the other fim recombinases rapidly expressed type 1 pili upon experimental
      infection. Finally, we found that disruption of leuX, but not loss of PAI
      II(UTI89) genes, reduced bladder epithelial invasion and intracellular
      proliferation, independent of type 1 piliation. These findings indicate that the
      predominant mechanism for preservation of PAI II(UTI89) during the establishment
      of acute cystitis is maintenance of wild-type leuX, and not PAI II(UTI89) gene
      content.

PMID- 18036140
TI  - The large subunit of Leishmania topoisomerase I functions as the 'molecular
      steer' in type IB topoisomerase.
AB  - Kinetoplastid topoisomerase IB is an unusual bisubunit enzyme where
      reconstitution of the large (LdTOPIL or L) and small (LdTOPIS or S) subunits
      shows functional activity. It is yet to be deciphered whether one subunit or both
      navigate the heterodimer to its cellular DNA targets. Tethering a specific DNA
      binding protein to topoisomerase I alters its site specificity. The chimeric
      constructs UMSBP-LdTOPIL/S or U-L/S (fusion of UMSBP to the N-terminus of L and
      reconstituted with S) and LdTOPIL/UMSBP-LdTOPIS or L/U-S (fusion of UMSBP to the
      N-terminus of S and reconstituted with L) exhibit relaxation activity. Only U-L/S
      shows altered site specificity and enhanced DNA-binding affinity for the
      universal minicircle sequence (UMS) containing substrate. This proves that L
      alone serves as the 'molecular steer' for this heterodimer. Reconstituted U-L/S
      also induces cleavage close to UMS and causes minicircle linearization. The
      differential properties of the reconstituted chimeras U-L/S and L/U-S reveal the
      structural and functional asymmetry between the heterodimer. Therefore this study
      helps in a better understanding of the mechanistic details underlying
      topoisomerization by this bi-subunit enzyme.

PMID- 18036141
TI  - Mutations in two global regulators lower individual mortality in Escherichia
      coli.
AB  - There has been considerable investigation into the survival of bacterial cells
      under stress conditions, but little is known about the causes of mortality in the
      absence of exogenous stress. That there is a basal frequency of cell death in
      such populations may reflect that it is either impossible to avoid all lethal
      events, or alternatively, that it is too costly. Here, through a genetic screen
      in the model organism Escherichia coli, we identify two mutants with lower
      frequencies of mortality: rssB and fliA. Intriguingly, these two genes both
      affect the levels of different sigma factors within the cell. The rssB mutant
      displays enhanced resistance to multiple external stresses, possibly indicating
      that the cell gains its increased vitality through elevated resistance to
      spontaneous, endogenous stresses. The loss of fliA does not result in elevated
      stress resistance; rather, its survival is apparently due to a decreased physical
      stress linked to the insertion of the flagellum through the membrane and energy
      saved through the loss of the motor proteins. The identification of these two
      mutants implies that reducing mortality is not impossible; rather, due to its
      cost, it is subject to trade-offs with other traits that contribute to the
      competitive success of the organism.

PMID- 18036142
TI  - Parental experiences and preferences which influence subsequent use of post
      discharge health services for children born very preterm.
AB  - AIM: Parents are ultimately responsible for organising and accessing health
      services for their children. How parents experience those services are likely to
      influence subsequent use. Understanding parental preference for service provision
      can inform compliance strategies with recommended child health recommendations.
      The aim of this study was to explore parental experiences and preferences which
      influence subsequent use of post-discharge health services for children born
      preterm with a birthweight < or =1250 g. METHODS: Focus groups consisted of
      randomly selected families recruited from a population-based cross-sectional
      cohort study of 2-, 4- and 7-year-old children corrected age for prematurity.
      Parents were asked to consider which aspects of childhood health service delivery
      influenced subsequent use. Transcripts were analysed and themes constructed. SWOT
      analysis evaluated health service practices by systematically mapping parents'
      accounts of the perceived strengths (S), weaknesses (W), opportunities (O) and
      threats (T) of services in relation to subsequent use. RESULTS: Fifteen parents
      participated in three groups (by children's age). Three dominant themes emerged
      and included (i) assistance with accessing appropriate services; (ii) provision
      of consistent information and comprehensive child health records; and (iii)
      support of parental self-efficacy in the health care of their child. CONCLUSION:
      Primary health carers are ideally suited to co-ordinate and provide continuity to
      improve parental involvement and compliance with health promoting recommendations
      for their preterm children. This approach may improve interagency co-operation
      and access to services enabling early identification and intervention. Adopting
      these strategies may be effective in optimising child health follow-up strategies
      and improve uptake of recommended intervention and prevention programmes.

PMID- 18036143
TI  - Prevalence and behavioural correlates of enuresis in young children.
AB  - OBJECTIVES: Previous studies based on clinical samples report that enuresis in
      children is associated with behavioural problems and reduced self-esteem, but the
      relationship between behavioural problems and enuresis remains controversial.
      This population-based study investigated the prevalence and behavioural
      correlates of enuresis in a group of preparatory school children. METHODS: This
      cross-sectional survey involved 356 parents and their children aged 5-7 years,
      all residents of Istanbul, Turkey. Parents completed the Child Behaviour
      Checklist and socio-demographic data form (response rate: 90%). Fifty-three
      children with enuresis were compared with 303 non-symptomatic children.
      Differences in the mean scores and the percentages of children falling beyond pre
      selected clinical thresholds were compared between the groups. RESULTS: The
      prevalence of enuresis was 14.9%, and enuresis was more frequent among boys.
      Children with enuresis were reported by their parents to have greater social
      problems and higher total problem scores than control children (P = 0.019, P =
      0.048, respectively). However, there were no differences in the percentages of
      children falling beyond pre-selected clinical thresholds between the groups.
      CONCLUSIONS: Children with enuresis had higher mean scores for total and social
      behavioural problems than controls; however, clinically relevant behavioural
      problems did not show differences between the groups. Given the inconsistent
      research findings across studies, longitudinal research and outcome studies could
      help determine whether there is a causal relationship between psychopathology and
      enuresis.

PMID- 18036144
TI  - Randomised controlled trial of intravenous maintenance fluids.
AB  - AIM: Traditional paediatric intravenous maintenance fluids are prescribed using
      hypotonic fluids and the weight-based 4:2:1 formula for administration rate.
      However, this may cause hyponatraemia in sick and post-operative children. We
      studied the effect of two types of intravenous maintenance fluid and two
      administration rates on plasma sodium concentration in intensive care patients.
      METHODS: A Factorial-design, double-blind, randomised controlled trial was used.
      We randomised 50 children with normal electrolytes without hypoglycaemia who
      needed intravenous maintenance fluids for >12 h to 0.9% saline (normal saline) or
      4% dextrose and 0.18% saline (dextrose saline), at either the traditional
      maintenance fluid rate or 2/3 of that rate. The main outcome measure was change
      in plasma sodium from admission to 12-24 h later. RESULTS: Fifty patients (37
      surgical) were enrolled. Plasma sodium fell in all groups: mean fall 2.3
      (standard deviation 4.0) mmol/L. Fluid type (P = 0.0063) but not rate (P = 0.12)
      was significantly associated with fall in plasma sodium. Dextrose saline produced
      a greater fall in plasma sodium than normal saline: difference 3.0, 95%
      confidence interval 0.8-5.1 mmol/L. Full maintenance rate produced a greater fall
      in plasma sodium than restricted rate, but the difference was small and non
      significant: 1.6 (-0.7, 3.9) mmol/L. Fluid type, but not rate, remained
      significant after adjustment for surgical status. One patient, receiving normal
      saline at restricted rate, developed asymptomatic hypoglycaemia. CONCLUSION: Sick
      and post-operative children given dextrose saline at traditional maintenance
      rates are at risk of hyponatraemia.

PMID- 18036145
TI  - A quality audit of the service delivered by the NSW Neonatal and Paediatric
      Transport Service.
AB  - AIM: To discover areas of NSW Neonatal and Paediatric Transport Service's (NETS)
      work with which the parents, referring and receiving doctors are dissatisfied and
      respond to them. METHODS: An anonymous survey of referring doctors, parents of
      patients transported by NETS and receiving hospital doctors between July and
      December 2005. RESULTS: Referring doctors: Fifty-seven per cent of the 288 (30%
      response rate) doctors who responded were paediatricians and 43% worked in rural
      settings. Over 90% responded positively about communication with the NETS team at
      referral and retrieval. Useful feedback included the need to be more time
      efficient in phone communication and during stabilisation of the child and to
      improve feedback about management and patient outcomes. Parents: Forty-seven per
      cent of 152 responses (15% response rate) came from rural families. The majority
      (>98%) of parents felt that the NETS team were helpful and supportive of them.
      Parents reported being able to travel with their child 60% of the time and of
      those who could not, 95% could explain why. Receiving doctors: Ninety-three per
      cent of 218 responses (42% response rate) thought that the referral was
      appropriate, that the NETS teams carried out their advice correctly (98%) and
      that the child's needs were reported accurately by the team (90%). In a minority
      of retrievals important concerns were raised about ventilation, sedation, patient
      assessment and management. CONCLUSION: Most retrievals happen in a way that
      referring consultants, parents and receiving consultants find appropriate.
      Important suggestions for improvement in service delivery and some areas of risk
      to patient safety have been identified. Processes for overcoming these situations
      are being developed and implemented.

PMID- 18036146
TI  - Undergraduate medical students' exposure to clinical ethics: a challenge to the
      development of professional behaviours?
AB  - CONTEXT: The objective of this research was to explore medical students'
      experience of challenges to their ethical knowledge and understanding in clinical
      practice, and to investigate their need and preference for support when faced
      with such challenges. METHODS: We carried out a cross-sectional survey using web
      based and paper questionnaires. Questions were designed using examples of ethical
      challenges identified in the previous literature. The study involved 3 UK
      university medical schools. All incorporate ethics teaching programmes in problem
      based learning curricula. Participants were 732 (30% of total) senior
      undergraduate medical students learning within the clinical environment. RESULTS:
      Students regularly experienced situations in clinical teaching settings that
      challenged their ethical values. Despite self-reports of good levels of
      confidence in their knowledge of ethical principles, medical students reported
      low levels of confidence in their ability to address these challenges, and
      perceived a need for additional support from clinical teachers. CONCLUSIONS:
      Complex and ethically challenging situations occur commonly in medical education.
      Many students feel that they do not currently access sufficient support from
      staff to address these. Clinical teachers were identified as the most relevant
      providers of guidance. The nature of medicine and its delivery makes it highly
      likely that medical students will come into contact with ethically challenging
      situations. Appropriate educational provision therefore requires medical
      educators to be equipped with the knowledge and the skills to engage with
      students' ethical concerns.

PMID- 18036147
TI  - Orthotopic transplantation of immortalized mesencephalic progenitors (CSM14.1
      cells) into the substantia nigra of hemiparkinsonian rats induces neuronal
      differentiation and motoric improvement.
AB  - Neural progenitor cell grafting is a promising therapeutic option in the
      treatment of Parkinson's disease. In previous experiments we grafted temperature
      sensitive immortalized CSM14.1 cells, derived from the ventral mesencephalon of
      E14-rats, bilaterally in the caudate putamen of adult hemiparkinsonian rats. In
      these studies we were not able to demonstrate either a therapeutic improvement or
      neuronal differentiation of transplanted cells. Here we examined whether CSM14.1
      cells grafted bilaterally orthotopically in the substantia nigra of
      hemiparkinsonian rats have the potential to differentiate into dopaminergic
      neurons. Adult male rats received 6-hydroxydopamine into the right medial
      forebrain bundle, and successful lesions were evaluated with apomorphine-induced
      rotations 12 days after surgery. Two weeks after a successful lesion the animals
      received bilateral intranigral grafts consisting of either about 50 000 PKH26
      labelled undifferentiated CSM14.1 cells (n = 16) or a sham-graft (n = 9).
      Rotations were evaluated 3, 6, 9 and 12 weeks post-grafting. Animals were finally
      perfused with 4% paraformaldehyde. Cryoprotected brain slices were prepared for
      immunohistochemistry using the freeze-thaw technique to preserve PKH26-labelling.
      Slices were immunostained against neuronal epitopes (NeuN, tyrosine hydroxylase)
      or glial fibrillary acidic protein. The CSM14.1-cell grafts significantly reduced
      the apomorphine-induced rotations 12 weeks post-grafting compared to the sham
      grafts (P < 0.05). There was an extensive mediolateral migration (400-700 microm)
      of the PKH26-labelled cells within the host substantia nigra. Colocalization with
      NeuN or glial fibrillary acidic protein in transplanted cells was confirmed with
      confocal microscopy. No tyrosine hydroxylase-immunoreactive grafted cells were
      detectable. The therapeutic effect of the CSM14.1 cells could be explained either
      by their glial cell-derived neurotrophic factor-expression or their neural
      differentiation with positive effects on the basal ganglia neuronal networks.

PMID- 18036148
TI  - Differential expression of duplicated VAL-opsin genes in the developing
      zebrafish.
AB  - Non-visual opsins mediate various light-dependent physiological events. Our
      previous search for non-visual opsin genes in zebrafish led to the discovery of
      VAL-opsin (VAL-opsinA) in deep brain cells and retinal horizontal cells of the
      adult fish. In this study, we report the identification and characterization of
      its duplicated gene, VAL-opsinB, in zebrafish. A molecular phylogenetic analysis
      indicates that VAL-opsinB is orthologous to a previously reported salmon gene and
      that the duplication of the VAL-opsin gene occurred in the teleost lineage. The
      recombinant protein of zebrafish VAL-opsinB forms a green-sensitive photopigment
      when reconstituted with 11-cis-retinal. VAL-opsinB expression was detected in a
      limited number of cells of the brain and the eye, and the expression pattern is
      distinct from that of the VAL-opsinA gene. Such a differential expression pattern
      suggests that VAL-opsinA and VAL-opsinB are involved in different physiological
      events in zebrafish.

PMID- 18036149
TI  - Spinal cord degeneration in C57BL/6N mice following induction of experimental
      parkinsonism with MPTP.
AB  - We examined neurodegeneration in spinal cord (SC) and role of such extra-nigral
      degeneration in MPTP-induced experimental parkinsonism in C57BL/6N mice. HPLC
      photodiode array analysis confirmed presence of the active neurotoxin MPP+ in SC
      after single injection of MPTP (25 mg/kg, i.p.). Mitochondrial enzyme monoamine
      oxidase-B (MAO-B) responsible for in vivo conversion of MPTP to MPP+ was
      inhibited in SC by pre-treatment with l-deprenyl, a specific inhibitor of MAO-B.
      Besides in vitro conversion of MPTP to MPP+ occurred by SC mitochondrial
      preparation, which was inhibited by l-deprenyl implicating SC as a specific
      target of MPTP-neurotoxicity. Double immunofluorescent labeling and
      spectrofluorimetric assay via kynuramine oxidation showed MAO-B expression and
      activity in SC neurons. Localization of dopamine transporter immunoreactivity in
      SC along with specific uptake of (3)H-MPP+ by SC synaptosomal preparation further
      confirmed SC as target of MPTP-neurotoxicity. Compared with control, increased
      neuronal death on the seventh day in SC of mice injected with MPTP (2 x 25 mg/kg,
      at 6 h interval) strongly suggested SC degeneration in pre-symptomatic phase of
      MPTP-induced experimental parkinsonism. Such extra-nigral neurodegeneration in
      Parkinson's disease indicated novel molecular mechanism preceding nigrostriatal
      degeneration and suggested designing broad therapeutic intervention for this
      complex movement disorder.

PMID- 18036150
TI  - Cross-linking of sites involved with alcohol action between transmembrane
      segments 1 and 3 of the glycine receptor following activation.
AB  - The glycine receptor is a member of the Cys-loop, ligand-gated ion channel family
      and is responsible for inhibition in the CNS. We examined the orientation of
      amino acids I229 in transmembrane 1 (TM1) and A288 in TM3, which are both
      critical for alcohol and volatile anesthetic action. We mutated these two amino
      acids to cysteines either singly or in double mutants and expressed the receptors
      in Xenopus laevis oocytes. We tested whether disulfide bonds could form between
      A288C in TM3 paired with M227C, Y228C, I229C, or S231C in TM1. Application of
      cross-linking (mercuric chloride) or oxidizing (iodine) agents had no significant
      effect on the glycine response of wild-type receptors or the single mutants. In
      contrast, the glycine response of the I229C/A288C double mutant was diminished
      after application of either mercuric chloride or iodine only in the presence of
      glycine, indicating that channel gating causes I229C and A288C to fluctuate to be
      within 6 A apart and form a disulfide bond. Molecular modeling was used to thread
      the glycine receptor sequence onto a nicotinic acetylcholine receptor template,
      further demonstrating that I229 and A288 are near-neighbors that can cross-link
      and providing evidence that these residues contribute to a single binding cavity.

PMID- 18036151
TI  - 5-HT and 5-HT-SO4, but not tryptophan or 5-HIAA levels in single feeding neurons
      track animal hunger state.
AB  - Serotonin (5-HT) is an intrinsic modulator of neural network excitation states in
      gastropod molluscs. 5-HT and related indole metabolites were measured in single,
      well-characterized serotonergic neurons of the feeding motor network of the
      predatory sea-slug Pleurobranchaea californica. Indole amounts were compared
      between paired hungry and satiated animals. Levels of 5-HT and its metabolite 5
      HT-SO4 in the metacerebral giant neurons were observed in amounts approximately
      four-fold and two-fold, respectively, below unfed partners 24 h after a satiating
      meal. Intracellular levels of 5-hydroxyindole acetic acid and of free tryptophan
      did not differ significantly with hunger state. These data demonstrate that
      neurotransmitter levels and their metabolites can vary in goal-directed neural
      networks in a manner that follows internal state.

PMID- 18036152
TI  - Reduced calcium-dependent mitochondrial damage underlies the reduced
      vulnerability of excitotoxicity-tolerant hippocampal neurons.
AB  - In central neurons, over-stimulation of NMDA receptors leads to excessive
      mitochondrial calcium accumulation and damage, which is a critical step in
      excitotoxic death. This raises the possibility that low susceptibility to calcium
      overload-induced mitochondrial damage might characterize excitotoxicity-resistant
      neurons. In this study, we have exploited two complementary models of
      preconditioning-induced excitotoxicity resistance to demonstrate reduced calcium
      dependent mitochondrial damage in NMDA-tolerant hippocampal neurons. We have
      further identified adaptations in mitochondrial calcium handling that account for
      enhanced mitochondrial integrity. In both models, enhanced tolerance was
      associated with improved preservation of mitochondrial membrane potential and
      structure. In the first model, which exhibited modest neuroprotection,
      mitochondria-dependent calcium deregulation was delayed, even though cytosolic
      and mitochondrial calcium loads were quantitatively unchanged, indicating that
      enhanced mitochondrial calcium capacity accounts for reduced injury. In contrast,
      the second model, which exhibited strong neuroprotection, displayed further
      delayed calcium deregulation and reduced mitochondrial damage because
      downregulation of NMDA receptor surface expression depressed calcium loading.
      Reducing calcium entry also modified the chemical composition of the calcium
      buffering precipitates that form in calcium-loaded mitochondria. It thus appears
      that reduced mitochondrial calcium loading is a major factor underlying the
      robust neuroprotection seen in highly tolerant cells.

PMID- 18036153
TI  - Anchoring TRP to the INAD macromolecular complex requires the last 14 residues in
      its carboxyl terminus.
AB  - Drosophila transient-receptor-potential (TRP) is a Ca2+ channel responsible for
      the light-dependent depolarization of photoreceptors. TRP is anchored to a
      macromolecular complex by tethering to inactivation-no-afterpotential D (INAD).
      We previously reported that INAD associated with the carboxyl tail of TRP via its
      third post-synaptic density protein 95, discs-large, zonular occludens-1 domain.
      In this paper, we further explored the molecular basis of the INAD interaction
      and demonstrated the requirement of the last 14 residues of TRP, with the
      critical contribution of Gly1262, Val1266, Trp1274, and Leu1275. We also revealed
      by pull-down assays that the last 14 residues of TRP comprised the minimal
      sequence that competes with the endogenous TRP from fly extracts, leading to the
      co-purification of a partial INAD complex containing INAD, no-receptor-potential
      A, and eye-protein kinase C (PKC). Eye-PKC is critical for the negative
      regulation of the visual signaling and was shown to phosphorylate TRP in vivo. To
      uncover the substrates of eye-PKC in the INAD complex, we designed a complex
      dependent eye-PKC assay, which utilized endogenous INAD complexes isolated from
      flies. We demonstrate that activated eye-PKC phosphorylates INAD, TRP but not no
      receptor-potential A. Moreover, phosphorylation of TRP is dependent on the
      presence of both eye-PKC and INAD. Together, these findings indicate that stable
      kinase-containing protein complexes may be isolated by pull-down assays, and used
      in this modified kinase assay to investigate phosphorylation of the proteins in
      the complex. We conclude that TRP associates with INAD via its last 14 residues
      to facilitate its regulation by eye-PKC that fine-tunes the visual signaling.

PMID- 18036154
TI  - Nitrated alpha-synuclein-activated microglial profiling for Parkinson's disease.
AB  - Microglial neuroinflammatory processes play a primary role in dopaminergic
      neurodegeneration for Parkinson's disease (PD). This can occur, in part, by
      modulation of glial function following activation by soluble or insoluble
      modified alpha-synuclein (alpha-syn), a chief component of Lewy bodies that is
      released from affected dopaminergic neurons. alpha-Syn is nitrated during
      oxidative stress responses and in its aggregated form, induces inflammatory
      microglial functions. Elucidation of these microglial function changes in PD
      could lead to new insights into disease mechanisms. To this end, PD-associated
      inflammation was modeled by stimulation of microglia with aggregated and nitrated
      alpha-syn. These activated microglia were ameboid in morphology and elicited
      dopaminergic neurotoxicity. A profile of nitrated, aggregated alpha-syn
      stimulated microglia was generated using combinations of genomic (microarrays)
      and proteomic (liquid chromatography-tandem mass spectrometry, differential gel
      electrophoresis, and protein array) assays. Genomic studies revealed a
      substantive role for nuclear factor-kappa B transcriptional activation.
      Qualitative changes in the microglial proteome showed robust increases in
      inflammatory, redox, enzyme, and cytoskeletal proteins supporting the genomic
      tests. Autopsy brain tissue acquired from substantia nigra and basal ganglia of
      PD patients demonstrated that parallel nuclear factor-kappa B-related
      inflammatory processes were, in part, active during human disease. Taken
      together, the transcriptome and proteome of nitrated alpha-syn activated
      microglia, shown herein, provide new potential insights into disease mechanisms.

PMID- 18036155
TI  - Proteolysis of multiple myelin basic protein isoforms after neurotrauma:
      characterization by mass spectrometry.
AB  - Neurotrauma, as in the case of traumatic brain injury, promotes protease over
      activation characterized by the select fragmentation of brain proteins. The
      resulting polypeptides are indicators of biochemical processes, which can be used
      to study post-injury dynamics and may also be developed into biomarkers. To this
      end, we devised a novel mass spectrometry approach to characterize post-injury
      calpain proteolytic processing of myelin basic protein (MBP), a biomarker of
      brain injury that denotes white matter damage and recovery. Our approach exceeds
      conventional immunological assays in its deconvolution of multiple protein
      isoforms, its absolute quantification of proteolytic fragments and its
      polypeptide selectivity. We quantified and characterized post-injury proteolytic
      processing of all MBP isoforms identified in adult rat cortex. Further, the
      translation of calpain-cleaved MBP into CSF was verified following brain injury.
      We ascertained that the exon-6 sequence of MBP resulted in a characteristic shift
      in gel migration for intact and fragmented protein alike. We also found evidence
      for a second post-TBI cleavage event within exon-2 and for the dimerization of
      the post-TBI 4.3 kDa fragment. Ultimately, the novel methodology described here
      can be used to study MBP dynamics and other similar proteolytic events of
      relevance to brain injury and other CNS processes.

PMID- 18036156
TI  - Modulation of neuropeptide Y and Y1 receptor expression in the amygdala by
      fluctuations in the brain content of neuroactive steroids during ethanol drinking
      discontinuation in Y1R/LacZ transgenic mice.
AB  - Previous studies have shown that GABAergic neuroactive steroids increase Y1
      receptor (Y1R) gene expression in the amygdala of Y1R/LacZ transgenic mice,
      harbouring the murine Y1R gene promoter linked to a LacZ reporter gene. As
      ethanol is known to increase GABAergic neuroactive steroids, we investigated the
      relationship between fluctuations in the brain content of neuroactive steroids
      induced by chronic voluntary ethanol consumption or ethanol discontinuation and
      both the level of neuropeptide Y (NPY) immunoreactivity and Y1R gene expression
      in the amygdala of Y1R/LacZ transgenic mice. Ethanol discontinuation (48 h) after
      voluntary consumption of consecutive solutions of 3%, 6%, 10% and 20% (v/v)
      ethanol over 4 weeks produced an anxiety-like behaviour as measured by elevated
      plus maze. Voluntary ethanol intake increased the cerebrocortical concentration
      of the progesterone metabolite 3alpha-hydroxy-5alpha-pregnan-20-one
      (3alpha,5alpha-TH PROG) that returned to control level 48 h after discontinuation
      of ethanol intake. Ethanol discontinuation significantly decreased NPY
      immunoreactivity and concomitantly increased Y1R/LacZ transgene expression in the
      amygdala, whereas chronic ethanol intake failed to affect these parameters. The
      5alpha-reductase inhibitor finasteride prevented both the increase in the
      cerebrocortical concentration of 3alpha,5alpha-TH PROG apparent after 4 weeks of
      ethanol intake and the changes in NPY immunoreactivity and transgene expression
      induced by ethanol discontinuation. Data suggest that 3alpha,5alpha-TH PROG plays
      an important role in the changes in NPY-Y1R signalling in the amygdala during
      ethanol discontinuation.

PMID- 18036157
TI  - Is the modulation of retinoid and retinoid-associated signaling a future
      therapeutic strategy in neurological trauma and neurodegeneration?
AB  - The complex molecular pathways that mediate the effects of vitamin A and its
      derivatives, are increasingly recognized as a component of the repair capacity
      that could be activated to induce protection and regeneration in the mature
      nervous tissue. Retinoid and retinoid-associated signaling plays an essential
      role in normal neurodevelopment and appears to remain active in the adult CNS. In
      this paper, we review evidence which supports the hypothesis of an activation of
      retinoid-associated signaling molecular pathways in the mature nervous tissue and
      its significance in the context of neurodegenerative, trauma-induced and
      psychiatric disorders, at spinal and supra-spinal levels. Finally, we summarize
      the potential therapeutic avenues based on the modulation of retinoid targets
      undergoing reactivation under conditions of acute injury and chronic degeneration
      in the central nervous system, and discuss some of the unresolved issues linked
      to this treatment strategy.

PMID- 18036158
TI  - Organism size promotes the evolution of specialized cells in multicellular
      digital organisms.
AB  - Specialized cells are the essence of complex multicellular life. Fossils allow us
      to study the modification of specialized, multicellular features such as jaws,
      scales, and muscular appendages. But it is still unclear what organismal
      properties contributed to the transition from undifferentiated organisms, which
      contain only a single cell type, to multicellular organisms with specialized
      cells. Using digital organisms I studied this transition. My simulations show
      that the transition to specialized cells happens faster in organism composed of
      many cells than in organisms composed of few cells. Large organisms suffer less
      from temporarily unsuccessful evolutionary experiments with individual cells,
      allowing them to evolve specialized cells via evolutionary trajectories that are
      unavailable to smaller organisms. This demonstrates that the evolution of simple
      multicellular organisms which are composed of many functionally identical cells
      accelerates the evolution of more complex organisms with specialized cells.

PMID- 18036160
TI  - Unsuspected osteomyelitis is frequent in persistent diabetic foot ulcer and
      better diagnosed by MRI than by 18F-FDG PET or 99mTc-MOAB.
AB  - AIM: Prevalence, optimal diagnostic approach and consequences of clinically
      unsuspected osteomyelitis in diabetic foot ulcers are unclear. Early diagnosis of
      this infection may be crucial to ensure correct management. METHODS: We conducted
      a prospective study in 20 diabetic patients with a chronic foot ulcer (>8 weeks)
      without antibiotic pretreatment and without clinical signs for osteomyelitis to
      assess the prevalence of clinically unsuspected osteomyelitis and to compare the
      value of magnetic resonance imaging (MRI), 18F-fluorodeoxyglucose positron
      emission tomography (18F-FDG PET) and 99mTc-labelled monoclonal antigranulocyte
      antibody scintigraphy (99mTc-MOAB). Those with suggestive scans underwent bone
      biopsy for histology (n = 7). RESULTS: Osteomyelitis was confirmed by biopsy in
      seven of the 20 clinically unsuspected foot ulcers. Presence of osteomyelitis was
      not related to age, ulcer size, ulcer duration, duration of diabetes or HbA1c. C
      reactive protein was slightly elevated in patients with osteomyelitis (35.1 +/-
      16.0 mg L(-1) vs. 12.2 +/- 2.6 mg L(-1) in patients with and without
      osteomyelitis respectively; P = 0.07). MRI was positive in six of the seven
      patients with proven osteomyelitis, whereas 18F-FDG PET and 99mTc-MOAB were
      positive only in (the same) two patients. Of the seven patients with
      osteomyelitis, five had lower limb amputation and in one patient the ulcer was
      persisting after 24 months of follow-up. In contrast, of the 13 patients without
      detectable signs of osteomyelitis on imaging modalities only two had lower limb
      amputation and two persisting ulcers. CONCLUSIONS: Clinically unsuspected
      osteomyelitis is frequent in persisting foot ulcers and is a high risk factor for
      adverse outcome. MRI appears superior to 18F-FDG PET and 99mTc-MOAB in detecting
      foot ulcer-associated osteomyelitis and might be the preferred imaging modality
      in patients with nonhealing diabetic foot ulcers.

PMID- 18036161
TI  - Heart valve disease associated with treatment with ergot-derived dopamine
      agonists: a clinical and echocardiographic study of patients with Parkinson's
      disease.
AB  - OBJECTIVE: To elucidate the association between treatment with ergot-derived
      dopamine agonists (EDDA) and valvular abnormalities amongst patients with
      idiopathic Parkinson's disease (IPD) and secondly, to analyse the yield of
      clinical screening for valvular heart disease. DESIGN: A cross-sectional
      controlled study. SETTING: The cohort of IPD patients treated in the outpatient
      clinic, Department of Neurology, Aarhus University Hospital, Denmark. SUBJECTS: A
      total of 138 IPD patients [median age 64 (39-87) years, 62% men] treated with
      either EDDA (n = 85) or non-EDDA (n = 53) for at least 6 months. Interventions.
      Patients were screened for valvular heart disease by clinical means and by
      examiner-blinded echocardiography. Main outcome measure was valvular
      regurgitation revealed by echocardiography. RESULTS: Severe aortic regurgitation
      (n = 4) or moderate aortic (n = 12), mitral (n = 3) or tricuspidal valve
      regurgitation (n = 5) was found in 22 EDDA patients (25.9%). Two patients had
      coexistent moderate mitral and tricuspid valvular regurgitation. Two non-EDDA
      patients had moderate valve insufficiency (3.8%, P < 0.05). The adjusted relative
      risk for at least moderate valve insufficiency in the EDDA patients was 7.2% (P <
      0.05). The sensitivity of detecting at least moderate valvular disease by cardiac
      murmur, dyspnoea, or the heart failure marker NT-proBNP (natriuretic peptide) was
      62% for the neurologists and 93% for the cardiologist but with equally low
      specificity (30-35%). CONCLUSION: EDDA was associated with a clinically important
      and statistically significant risk of at least moderate valve regurgitation.
      Clinical screening for valve disease was inadequate and it seems advisable to
      offer EDDA patients control with echocardiography.

PMID- 18036162
TI  - A note of caution for the doctor on duty: take the acute attack in chronic
      pancreatitis seriously!

PMID- 18036163
TI  - Secondary prevention of cardiovascular disease in type 2 diabetes and
      prediabetes: a cardiologist's perspective.
AB  - Patients with type 2 diabetes mellitus (T2DM) and prediabetes have a
      substantially greater risk of developing cardiovascular (CV) disease than the
      general population. This increased risk of CV disease is due to a complex cluster
      of risk factors including insulin resistance, hyperglycaemia, diabetic
      dyslipidaemia, hypertension and systemic inflammation. As a result of this
      cluster of risk factors, life expectancy is reduced by up to 10 years upon
      diagnosis of T2DM, principally because of fatal CV events. Patients with T2DM are
      not only more likely to sustain a CV event, but also have a higher risk of a
      fatal outcome from this event. Therefore, whilst primary prevention is critical
      in determining the prognosis of patients newly diagnosed with T2DM, many will go
      on to suffer CV events and represent a high-risk group requiring intensive
      secondary prevention techniques. Recent data demonstrate that contemporary
      prevention therapies do not afford equal benefits to T2DM sufferers after acute
      myocardial infarction compared with their non-diabetic counterparts. This finding
      highlights the need for more effective secondary preventative strategies to
      prevent recurrent CV events in patients with T2DM and prediabetes. The
      cardiologist's role in the multidisciplinary management of T2DM is to improve
      patient outcomes by optimising use of evidence-based strategies for the
      prevention of recurrent CV events.

PMID- 18036164
TI  - Solifenacin treatment for overactive bladder in Hispanic patients: patient
      reported symptom bother and quality of life outcomes from the VESIcare Open-Label
      Trial.
AB  - OBJECTIVE: The primary goal of overactive bladder (OAB) treatment is to reduce
      symptoms and improve health-related quality of life (HRQoL). Although trials open
      enrolment to everyone, most OAB studies feature Caucasians. Here we present
      Hispanic data. METHODS: VESIcare Open-Label Trial was a 12-week, open-label,
      flexible-dosing study in patients with OAB symptoms for >or=3 months. All
      patients started on solifenacin 5 mg/day, with a dosing option of 5 or 10 mg/day
      at weeks 4 and 8. Three patient-reported outcome (PRO) measures assessed symptom
      improvement and treatment satisfaction: the Patient Perception of Bladder
      Condition (PPBC) scale, a Visual Analogue Scale (VAS), the Overactive Bladder
      Questionnaire (OAB-q). RESULTS: 94/2205 patients in the full population were
      Hispanic. Urgency was most frequently reported at baseline (93.6%), followed by
      frequency (91.5%), nocturia (84.0%) and urge incontinence (UI) (67.0%). Frequency
      was reported as the most bothersome symptom (MBS) by a higher proportion of
      Hispanics than the full population (40.4% vs. 28.1%). UI was reported as the MBS
      by a smaller proportion of Hispanics (18.1% vs. 27.3%). Patients reporting
      moderate-to-severe problems related to bladder condition at baseline reported
      improvement to 'some minor problems' at week 12. Over 72.0% of patients
      experienced PPBC score improvement. Both groups reported significant improvements
      in urgency, UI, frequency and nocturia on the VAS (all p<0.001) and all OAB-q
      domains (all p<0.001) at week 12. CONCLUSION: Although numbers were small,
      Hispanics receiving solifenacin for OAB reported improvement from baseline in
      symptom bother and HRQoL, as assessed by three independent PRO measures.

PMID- 18036165
TI  - Increased 5-year mortality in the migrant South Asian stroke patients with
      diabetes mellitus in the United Kingdom: the West Birmingham Stroke Project.
AB  - BACKGROUND: Stroke is a major cause of premature mortality in Britain, but its
      burden is markedly greater amongst South Asians. Because of the paucity of data
      in this area, we investigated the magnitude and impact of risk from
      cardiovascular comorbidities on survival amongst South Asian stroke patients.
      METHODS: We reviewed hospital case records of consecutive first in life time
      ischaemic stroke patients [self reported ethnicity and International
      Classification of Disease (ICD) 10th revision, codes 430-438] admitted to an
      inner city hospital in the UK between 1997 and 2001. In-hospital mortality data
      and CVD risk factors were analysed. Five-year mortality data was obtained from
      the National Health Tracing Services. RESULTS: Of 1474 ischaemic stroke patients,
      242 (16%) were South Asian of whom, 143 (59.1%) were male. The prevalence of
      hypertension was 70.2%, followed by diabetes 56.2%, hyperlipidaemia 7% and
      myocardial infarction 10.3%. At 5 years follow-up, 40.5% had died. Cumulative
      event-free survival at 5 years was significantly poorer in patients with diabetes
      (log-rank test, p=0.009). On Cox regression analysis, incorporating age, gender
      and other CVD risk factors, diabetes mellitus was an independent predictor of
      mortality odds ratio=1.65 (1.02-2.6, p=0.039). Hypertension and dyslipidaemia did
      not discriminate survival amongst South Asian patients. CONCLUSION: Stroke
      mortality in South Asians is associated with presence of diabetes mellitus. This
      highlights the significance of early and intensive CVD risk modification
      strategies in ethnic minorities particularly in patients with diabetes. Further
      research is warranted in South Asians to examine the underlying basis and related
      pathophysiological abnormalities.

PMID- 18036166
TI  - Efficacy and safety of high concentration lidocaine for trigeminal nerve block in
      patients with trigeminal neuralgia.
AB  - AIMS: Local anaesthetics, which act as neurolytics and Na(+) channel blockers,
      have been used for disrupting the neural firings in certain neuropathic pain
      conditions. This study was undertaken to investigate the clinical outcome of
      trigeminal nerve block with 10% lidocaine in the management of trigeminal
      neuralgia (TN). METHODS: Thirty-five patients with primary TN received trigeminal
      nerve blocks with 10% lidocaine. Success was defined as complete pain relief or
      mild pain without medication 1 day after the treatment. We followed the patients
      up every 2 months assessing for pain recurrence, sensory changes and other
      complications for a total of 37-45 months (median 43 months). RESULTS: Twelve of
      the 35 patients (34.3%) responded favourably to the treatment and were considered
      as success. Eleven patients experienced complete pain relief and one could
      tolerate pain without medication 1 day after the blocks, which lasted for 3-172
      weeks. Four patients experienced mildly decreased sensation in the region of the
      face supplied by the nerve 1 day after the blocks; however, all recovered normal
      skin sensation in 6 months. There was neither allodynia nor other sensory
      discomfort. The pain intensity and current pain duration before treatment were
      significantly different between the two groups. CONCLUSION: Trigeminal nerve
      block with high concentration lidocaine (10%) is capable of achieving an
      intermediate period of pain relief, particularly in patients with lower pain
      intensity and shorter pain duration prior to the procedure.

PMID- 18036167
TI  - Xanthelasma is not associated with increased risk of carotid atherosclerosis in
      normolipidaemia.
AB  - OBJECTIVES: Extracranial carotid artery (ECCA) atherosclerosis is well known to
      be associated with cardiovascular diseases. This study aims to investigate the
      difference of ECCA atherosclerosis between patients with xanthelasma and control
      subjects in normolipidaemia. METHODS: Carotid atherosclerosis (CA) of 41 (8 males
      and 33 females) patients with xanthelasma and normolipidaemia, defined as levels
      of cholesterol below 6.21 mmol/l and triglyceride below 2.26 mmol/l, recruited
      from Department of Dermatology was compared with that of 85 age- and gender
      matched control subjects. The extent and severity of CA were measured by high
      resolution B-mode ultrasound and expressed as the mean intima-media thickness
      (IMT) of the common carotid artery (CCA) and ECCA plaque score. Mixed-effects
      model and multivariate logistic regression analyses were used to estimate the
      association between xanthelasma and CA. RESULTS: Patients with xanthelasma showed
      significantly higher levels of low-density lipoprotein cholesterol (LDL-C) levels
      and higher body mass index (BMI) compared with the control group. Mixed models
      identified age, male gender, smoking and subjects of hypertension with
      medication, but not the presence of xanthelasma, were associated with an increase
      of CCA IMT. Multivariate logistic regression analysis revealed subjects of male
      gender, and hypertension with medication, but not the presence of xanthelasma,
      associated with thicker IMT, defined as IMT >or= 75th percentile, or ECCA plaque
      score >or= 3. CONCLUSIONS: Normolipidaemia with xanthelasma is not significantly
      associated with CA, but did relate with adverse cardiovascular profiles, such as
      higher BMI, waist circumference and LDL-C levels.

PMID- 18036168
TI  - Pericardiocentesis practice in the United Kingdom.
AB  - BACKGROUND: Pericardial effusions frequently present challenging clinical
      dilemmas. Whether or not to drain an effusion, and if so by what method, are two
      common decisions facing cardiologists. We performed a survey to evaluate
      pericardiocentesis practice in the United Kingdom (UK). METHODS: A total of 640
      questionnaires were sent to all cardiologists in the UK Directory of Cardiology
      in March 2003. RESULTS: A total of 274 (43%) completed questionnaires were
      returned, 88% from consultants, equally distributed between tertiary referral
      centres and district general hospitals. More than 1500 procedures were performed,
      largely using a paraxiphoid approach (89%). Clinical tamponade was the commonest
      indication for pericardiocentesis (83%). However, the majority of respondents
      (69%) considered echocardiographic features alone an indication for
      pericardiocentesis, even in the absence of clinical tamponade. The commonest
      perceived indications for drainage were right ventricular diastolic collapse and
      right atrial collapse (69% and 33% of respondents respectively). For guidance,
      82% use echocardiography, either alone or with fluoroscopy or the
      electrocardiogram (ECG) injury trace. 11% employ fluoroscopy alone or with the
      ECG injury trace. The remaining 11% stated that they would use the ECG injury
      trace alone or use no guidance. Using the ECG injury trace alone is said by the
      European Society of Cardiology (ESC) guidelines to offer an inadequate safeguard.
      Reported complications included ventricular puncture (n = 12, 0.8%) and hepatic
      damage (n = 4, 0.3%). CONCLUSION: Pericardiocentesis practice varies
      substantially in the UK. Many cardiologists would perform pericardiocentesis
      based on echocardiographic features alone. 11% of cardiologists use guidance that
      is considered inadequate by the ESC guidelines.

PMID- 18036169
TI  - Coexistence of interstitial cell of Cajal hyperplasia and microcarcinoidosis in a
      mature cystic teratoma of the ovary.

PMID- 18036170
TI  - DCIS with foreign body giant cells as a sign of 'healing' phenomenon--a case
      report.

PMID- 18036171
TI  - Simple, inexpensive and precise paraffin tissue microarrays constructed with
      predrilled ordinary steel embedding moulds.

PMID- 18036173
TI  - Inability to validate an association between CD23 expression and site or grade of
      follicular lymphoma.

PMID- 18036174
TI  - Nodular histiocytic/mesothelial hyperplasia on transthoracic biopsy: another
      source of potential pitfall in a lesion frequently present in spontaneous
      pneumothorax.

PMID- 18036175
TI  - Profiling and classification tree applied to renal epithelial tumours.
AB  - AIMS: Selection of the relevant combination from a growing list of candidate
      immunohistochemical biomarkers constitutes a real challenge. The aim was to
      establish the minimal subset of antibodies to achieve classification on the basis
      of 12 antibodies and 309 renal tumours. METHODS AND RESULTS: Seventy-nine clear
      cell (CC), 88 papillary (PAP) and 50 chromophobe (CHRO) renal cell carcinomas,
      and 92 oncocytomas (ONCO) were immunostained for renal cell carcinoma antigen,
      vimentin, cytokeratin (CK) AE1-AE3, CK7, CD10, epithelial membrane antigen, alpha
      methylacyl-CoA racemase (AMACR), c-kit, E-cadherin, Bcl-1, aquaporin 1 and mucin
      1 and analysed by tissue microarrays. First, unsupervised hierarchical clustering
      performed with immunohistochemical profiles identified four main clusters-cluster
      1 (CC 67%), 2 (PAP 98%), 3 (CHRO 67%) and 4 (ONCO 100%)-demonstrating the
      intrinsic classifying potential of immunohistochemistry. A series of
      classification trees was then automatically generated using Classification And
      Regression Tree software. The most powerful of these classification trees
      sequentially used AMACR, CK7 and CD10 (with 86% CC, 87% PAP, 79% CHRO and 78%
      ONCO correctly classified in a leave-one-out cross-validation test). The
      classifier was also helpful in 22/30 additional cases with equivocal features.
      CONCLUSION: The classification tree method using immunohistochemical profiles can
      be applied successfully to construct a renal tumour classifier.

PMID- 18036176
TI  - An upstream regulator and downstream target of phospholipase D1 activity during
      pheromone response in Saccharomyces cerevisiae.
AB  - Phospholipase D1 (PLD1), which is the product of the SPO14 gene, has been shown
      to play a role in the process of polarized cell growth (PCG) during the pheromone
      response in Saccharomyces cerevisiae. PLD1 hydrolyzes phosphatidylcholine to
      produce phosphatidic acid (PA) and a free choline headgroup. This study
      investigated the interactions of PLD1 and PA with two proteins known to be
      involved in the cellular signaling leading to PCG in yeast, the small GTPase
      Cdc42p and the PAK family kinase Ste20p. Constitutively activated Cdc42p
      stimulates PLD1 activity. Protein-lipid binding blots confirmed the specific
      binding of Ste20p to the PLD1 product, PA. Finally, kinase activity assays
      provided evidence for the stimulation of Ste20p by PA. These findings highlight
      the important interactions among PLD1, Cdc42p and Ste20p during PCG in S.
      cerevisiae.

PMID- 18036177
TI  - Glucose utilization of strains lacking PGI1 and expressing a transhydrogenase
      suggests differences in the pentose phosphate capacity among Saccharomyces
      cerevisiae strains.
AB  - Saccharomyces cerevisiae strains lacking phosphoglucose isomerase (pgi1) cannot
      use the pentose phosphate (PP) pathway to oxidize glucose, which has been
      explained by the lack of mechanism for reoxidation of the NADPH surplus.
      Consistent with this, the defective growth on glucose of a ENYpgi1 strain can be
      partially restored by expressing the Escherichia coli transhydrogenase udhA. In
      this work it was found that growth of V5 (wine yeast-derived) and FY1679
      (isogenic to S288C) pgi1 mutants is not rescued by expression of udhA. Moreover,
      the flux through the PP pathway of 11 S. cerevisiae strains from various origins
      was estimated, by calculating the ratio between the enzymatic activity of the
      G6PDH and HXK, placed at the glycolysis-PP pathway branch point. The results show
      that ENY.WA-1A exhibited the highest ratio (1.5-3-fold) and the highest G6PDH
      activity. Overexpression of ZWF1 encoding the G6PDH in V5pgi1udhA did not rescue
      growth on glucose, suggesting that steps downstream the G6PDH might limit the PP
      pathway in this strain. As a whole, these data highlight a great intraspecies
      diversity in the PP pathway capacity among S. cerevisiae strains and suggest that
      a low capacity may be the prime limiting factor in glucose oxidation through this
      pathway.

PMID- 18036178
TI  - Role of TLR1 and TLR6 in the host defense against disseminated candidiasis.
AB  - Toll-like receptor-1 (TLR1) and TLR6 are receptors of the TLR family that form
      heterodimers with TLR2. The role of TLR1 and TLR6 for the recognition of the
      fungal pathogen Candida albicans was investigated. TLR1 is not involved in the
      recognition of C. albicans, and TLR1 knock-out (TLR1-/-) mice showed a normal
      susceptibility to disseminated candidiasis. In contrast, recognition of C.
      albicans by TLR6 modulated the balance between Th1 and Th2 cytokines, and TLR6
      knock-out mice displayed a defective production of IL-10 and an increased IFN
      gamma release. Production of the monocyte-derived cytokines tumor necrosis
      factor, IL-1, and IL-6 was normal in TLR6-/- mice, and this was accompanied by a
      normal susceptibility to disseminated candidiasis. In conclusion, TLR6 is
      involved in the recognition of C. albicans and modulates the Th1/Th2 cytokine
      balance, but this results in a mild phenotype with a normal susceptibility of
      TLR6-/- mice to Candida infection.

PMID- 18036179
TI  - Comparative transcriptome analysis of responses of Methanothermobacter
      thermautotrophicus to different environmental stimuli.
AB  - Methanothermobacter thermautotrophicus strain DeltaH is a model hydrogenotrophic
      methanogen, for which the complete genome sequence and extensive biochemical
      information are available. Little is known, however, about how this organism
      regulates its cellular functions in response to environmental stimuli. In this
      study, whole-genome oligonucleotide microarrays were constructed for M.
      thermautotrophicus and used to gain insights into how this organism responds to
      different environmental stimuli, including hydrogen depletion, shifts in pH and
      temperature and the occurrence of toxics (hydrogen peroxide and ammonia). Our
      analysis confirmed that methanogenesis genes (including mtd, mer, frh and mcr)
      were upregulated under hydrogen-limited conditions, while some of them were
      affected by other environmental stimuli. Concerning stress responses of this
      organism, several unique features were revealed. First, there was no universal
      stress response in this organism. Second, genes for alternative redox enzymes,
      such as rubrerythrin, were upregulated under the oxidative stress, but those for
      typical antioxidant enzymes were not. Third, genes relevant to the modification
      of cell surface structures were differentially expressed under stress conditions.
      Finally, energy-requiring CO(2) assimilation systems were downregulated under
      stress conditions. These findings suggest that M. thermautotrophicus has complex
      transcriptional regulation mechanisms that facilitate it to survive in unstable
      ecosystems such as an anaerobic digester.

PMID- 18036180
TI  - Ecological diversification in the Bacillus cereus Group.
AB  - The Bacillus cereus Group comprises organisms that are widely distributed in the
      environment and are of health and economic interest. We demonstrate an 'ecotypic'
      structure of populations in the B. cereus Group using (i) molecular data from
      Fluorescent Amplified Fragment Length Polymorphism patterns, ribosomal gene
      sequences, partial panC gene sequences, 'psychrotolerant' DNA sequence signatures
      and (ii) phenotypic and descriptive data from range of growth temperature,
      psychrotolerance and thermal niches. Seven major phylogenetic groups (I to VII)
      were thus identified, with ecological differences that provide evidence for a
      multiemergence of psychrotolerance in the B. cereus Group. A moderate
      thermotolerant group (VII) was basal to the mesophilic group I, from which in
      turn distinct thermal lineages have emerged, comprising two mesophilic groups
      (III, IV), an intermediate group (V) and two psychrotolerant groups (VI, II).
      This stepwise evolutionary transition toward psychrotolerance was particularly
      well illustrated by the relative abundance of the 'psychrotolerant' rrs signature
      (as defined by Pruss et al.) copies accumulated in strains that varied according
      to the phylogenetic group. The 'psychrotolerant' cspA signature (as defined by
      Francis et al.) was specific to group VI and provided a useful way to
      differentiate it from the psychrotolerant group II. This study illustrates how
      adaptation to novel environments by the modification of temperature tolerance
      limits has shaped historical patterns of global ecological diversification in the
      B. cereus Group. The implications for the taxonomy of this Group and for the
      human health risk are discussed.

PMID- 18036181
TI  - The Toll-like receptors TLR2 and TLR4 do not affect the intestinal microbiota
      composition in mice.
AB  - The interaction between intestinal epithelial cells and microbes is partly
      mediated by Toll-like receptors (TLRs). Sensing of Gram-positive and Gram
      negative bacteria by TLR2 and TLR4, respectively, can result in immune system
      activation and in an exclusion of bacteria from the intestine. To test the impact
      of these TLRs on bacterial composition, germ-free TLR2/TLR4 double-knock out mice
      and the corresponding C57BL/10ScSn wild-type mice where associated with fecal
      bacteria from one single donor mouse. In addition, C3H/HeOuJ and BALB/c mice were
      used in this study. Fecal bacteria were monitored over 13 weeks with denaturing
      gradient gel electrophoresis (DGGE). Colonic bacteria were enumerated by
      fluorescent in situ hybridization (FISH) and short-chain fatty acids (SCFA) were
      measured in caecal samples. No effect of the TLRs on intestinal microbiota
      composition and SCFA concentrations was observed. However, the microbiota
      composition as reflected by DGGE band patterns differed between C3H and BALB/c
      mice on the one hand and C57BL/10 mice on the other hand. Corresponding
      differences between the mouse strains were also observed in cecal propionic,
      valeric and i-valeric acid concentrations. No differences between the animals
      were observed in the numbers of bacteria detected by FISH. We conclude that
      genetic traits but not TLR2 and TLR4 have an impact on the intestinal microbiota
      composition.

PMID- 18036182
TI  - Global diversity of island floras from a macroecological perspective.
AB  - Islands harbour a significant portion of all plant species worldwide. Their biota
      are often characterized by narrow distributions and are particularly susceptible
      to biological invasions and climate change. To date, the global richness pattern
      of islands is only poorly documented and factors causing differences in species
      numbers remain controversial. Here, we present the first global analysis of 488
      island and 970 mainland floras. We test the relationship between island
      characteristics (area, isolation, topography, climate and geology) and species
      richness using traditional and spatial models. Area is the strongest determinant
      of island species numbers (R(2) = 0.66) but a weaker predictor for mainlands
      (R(2) = 0.25). Multivariate analyses reveal that all investigated variables
      significantly contribute to insular species richness with area being the
      strongest followed by isolation, temperature and precipitation with about equally
      strong effects. Elevation and island geology show relatively weak yet significant
      effects. Together these variables account for 85% of the global variation in
      species richness.

PMID- 18036183
TI  - Is FOXP3 expressed in cutaneous T-cell lymphomas?

PMID- 18036184
TI  - Evaluation of bone disease in multiple myeloma patients carrying the t(4;14)
      chromosomal translocation.
AB  - T(4;14) chromosomal abnormality is one of the most adverse prognostic factors
      predicting for poor outcome in multiple myeloma (MM) patients. It has been
      recently suggested that bone disease, as evaluated by spinal magnetic resonance
      imaging (MRI), is relatively infrequent in these patients. In the present study,
      we aimed at further testing this hypothesis by analyzing the extent of whole bone
      involvement in patients showing t(4;14) chromosomal translocation as compared
      with negative patients. For this purpose, 53 consecutive newly diagnosed MM
      patients (35M, 18F, median age = 55 yr) underwent evaluation of total skeletal X
      ray, whole spine MRI, and at the same time, quantification of markers of bone
      resorption (urinary N-terminal telopeptide, pyridinoline, deoxypyridinoline,
      serum crosslaps), and bone formation (bone alkaline phosphatase and osteocalcin)
      was performed. The presence of IgH/MMSET fusion gene as a surrogate marker for
      t(4;14), was detected in 11 patients (20.7%), whose clinical characteristics were
      similar to those observed in t(4;14) negative patients. The type of marrow
      involvement at spinal MRI (diffuse vs. focal vs. negative) was the same in both
      groups of patients, even though overt vertebral fractures were more frequently
      found in t(4;14) positive cases (82% vs. 43%, P = 0.05); in line with this
      finding, skeletal lesions were more common in t(4;14) positive patients (mean
      skeletal score = 8.54 +/- 1.36 SE, as compared with 3.42 +/- 0.57 SE in t(4;14)
      negative cases, P = 0.000). These data were confirmed by the evaluation of serum
      crosslaps, that were significantly increased in patients with t(4;14) abnormality
      as compared with negative individuals (10,400 pmol/L +/- 2160 SE vs. 5640 pmol/L
      +/- 859 SE P = 0.02) Our results indicate that, at variance to what has been
      previously reported, bone resorption is more prominent in t(4;14) positive
      patients.

PMID- 18036185
TI  - Venous thromboembolism and subsequent short-term risk of an occult cancer.

PMID- 18036186
TI  - Type 2M von Willebrand disease: a variant of type 2A?

PMID- 18036187
TI  - Inhibitor incidence with recombinant vs. plasma-derived FVIII in previously
      untreated patients with severe hemophilia A: homogeneous results from four
      published observational studies.

PMID- 18036188
TI  - C reactive protein and its determinants in healthy men and women from European
      regions at different risk of coronary disease: the IMMIDIET Project.
AB  - AIM: Differences in C-reactive protein (CRP) levels and its determinants in three
      European populations at different risk of coronary artery disease (CAD) were
      studied. METHODS: Subjects were recruited randomly in Limburg (Belgium), Abruzzo
      (Italy) and south-west (SW) London (England). RESULTS: Ten-year risk of fatal
      coronary events (estimated using risk equations provided by the SCORE Project)
      was lower both in men and women from Abruzzo, intermediate in people from Limburg
      and higher in subjects from SW London. Within each country, high sensitivity (hs)
      CRP levels were higher in the high-risk class in men but not in women. Men from
      Abruzzo had higher hs-CRP levels than those from Limburg and SW London. Women
      always had higher hs-CRP levels than men. The strongest hs-CRP determinant was
      body mass index (BMI, R(2) = 0.14) in women and waist circumference (WC, R(2) =
      0.046) in men. The highest hs-CRP levels were observed in subjects with both high
      BMI and high WC. Metabolic syndrome was associated with high levels of CRP both
      in men and women, even after adjustment for confounders. DISCUSSION: Difference
      in CRP levels cannot explain the European gradient of CVD risk, although CRP
      levels are associated with the calculated SCORE risk of fatal coronary events
      within each country.

PMID- 18036189
TI  - Testing aspirin resistance using the Platelet Function Analyzer-100: some
      methodological caveats and considerations.

PMID- 18036190
TI  - A viable mouse model of factor X deficiency provides evidence for maternal
      transfer of factor X.
AB  - BACKGROUND: Activated factor X (FXa) is a vitamin K-dependent serine protease
      that plays a pivotal role in blood coagulation by converting prothrombin to
      thrombin. There are no reports of humans with complete deficiency of FX, and
      knockout of murine F10 is embryonic or perinatal lethal. OBJECTIVE: We sought to
      generate a viable mouse model of FX deficiency. METHODS: We used a socket
      targeting construct to generate F10-knockout mice by eliminating F10 exon 8
      (knockout allele termed F10(tm1Ccmt), abbreviated as '-'; wild-type '+'), and a
      plug-targeting construct to generate mice expressing a FX variant with normal
      antigen levels but low levels of FX activity [4-9% normal in humans carrying the
      defect, Pro343-->Ser, termed FX Friuli (mutant allele termed F10(tm2Ccmt),
      abbreviated as F)]. RESULTS: F10 knockout mice exhibited embryonic or perinatal
      lethality. In contrast, homozygous Friuli mice [F10 (F/F)] had FX activity levels
      of approximately 5.5% (sufficient to rescue both embryonic and perinatal
      lethality), but developed age-dependent iron deposition and cardiac fibrosis.
      Interestingly, F10 (-/F) mice with FX activity levels of 1-3% also showed
      complete rescue of lethality. Further study of this model provides evidence
      supporting a role of maternal FX transfer in the embryonic survival. CONCLUSIONS:
      We demonstrate that, while complete absence of FX is incompatible with murine
      survival, minimal FX activity as low as 1-3% is sufficient to rescue the lethal
      phenotype. This viable low-FX mouse model will facilitate the development of FX
      directed therapies as well as investigation of the FX role in embryonic
      development.

PMID- 18036191
TI  - Seizure resistance in fat-1 transgenic mice endogenously synthesizing high levels
      of omega-3 polyunsaturated fatty acids.
AB  - N-3 polyunsaturated fatty acids (PUFA), derived from marine oils, have been shown
      to protect against various neurological diseases. However, very little is known
      about their potential anticonvulsant properties. The objective of the present
      study was to determine whether enrichment of brain lipids with n-3 PUFA inhibits
      seizures induced by pentylenetetrazol. We demonstrate that increased brain levels
      of n-3 PUFA in transgenic fat-1 male mice, which are capable of de novo synthesis
      of n-3 PUFA from n-6 PUFA, increases latency to seizure onset by 45%, relative to
      wildtype controls (p = 0.08). Compared with wildtype littermates, transgenic fat
      1 mice have significantly (p < 0.05) higher levels of docosahexaenoic acid and
      total n-3 PUFA in brain total lipid extracts and phospholipids. Levels of brain
      docosahexaenoic acid were positively correlated to seizure latency (p < 0.05).
      These findings demonstrate that n-3 PUFA have anticonvulsant properties and
      suggest the possibility of a novel, non-drug dietary approach for the treatment
      of epilepsy.

PMID- 18036192
TI  - Lysophosphatidic acid-LPA1 receptor-Rho-Rho kinase-induced up-regulation of
      Nav1.7 sodium channel mRNA and protein in adrenal chromaffin cells: enhancement
      of 22Na+ influx, 45Ca2+ influx and catecholamine secretion.
AB  - In cultured bovine adrenal chromaffin cells, chronic (> or = 24 h) treatment with
      lysophosphatidic acid (LPA) augmented veratridine-induced 22Na+ influx via
      Na(v)1.7 by approximately 22% (EC(50) = 1 nmol/L), without changing nicotine
      induced 22Na+ influx via nicotinic receptor-associated channel. LPA enhanced
      veratridine (but not nicotine)-induced 45Ca2+ influx via voltage-dependent
      calcium channel and catecholamine secretion. LPA shifted concentration-response
      curve of veratridine for 22Na+ influx upward, without altering the EC(50) of
      veratridine. Ptychodiscus brevis toxin-3 allosterically enhanced veratridine
      induced 22Na+ influx by twofold in non-treated and LPA-treated cells. Whole-cell
      patch-clamp analysis showed that peak Na+ current amplitude was greater by 39% in
      LPA (100 nmol/L for 36 h)-treated cells; however, I-V curve and steady-state
      inactivation/activation curves were comparable between non-treated and LPA
      treated cells. LPA treatment (> or = 24 h) increased cell surface [3H]saxitoxin
      binding by approximately 28%, without altering the K(d) value; the increase was
      prevented by cycloheximide, actinomycin D, or Ki16425, dioctylglycerol
      pyrophosphate 8:0 (two inhibitors of LPA(1) and LPA3 receptors), or botulinum
      toxin C3 (Rho inhibitor), Y27632 (Rho kinase inhibitor), consistent with LPA(1)
      receptor expression in adrenal chromaffin cells. LPA raised Nav1.7 mRNA level by
      approximately 37%. Thus, LPA-LPA(1) receptor-Rho/Rho kinase pathway up-regulated
      cell surface Nav1.7 and Nav1.7 mRNA levels, enhancing veratridine-induced Ca2+
      influx and catecholamine secretion.

PMID- 18036193
TI  - Role of tissue plasminogen activator in the sensitization of methamphetamine
      induced dopamine release in the nucleus accumbens.
AB  - We have previously demonstrated that repeated, but not acute, methamphetamine
      (METH) treatment increases tissue plasminogen activator (tPA) activity in the
      brain, which is associated with the development of behavioral sensitization to
      METH. In this study, we investigated whether the tPA-plasmin system is involved
      in the development of sensitization in METH-induced dopamine release in the
      nucleus accumbens (NAc). There was no difference in acute METH-induced increase
      in extracellular dopamine levels in the NAc between wild-type and tPA-deficient
      (tPA-/-) mice. Repeated METH treatment resulted in a significant enhancement of
      METH- induced dopamine release in wild-type mice, but not tPA-/- mice.
      Microinjection of exogenous tPA or plasmin into the NAc of wild-type mice
      significantly potentiated acute METH- induced dopamine release. Degradation of
      laminin was evident in brain tissues incubated with tPA plus plasminogen or
      plasmin in vitro although tPA or plasminogen alone had no effect.
      Immunohistochemical analysis revealed that microinjection of plasmin into the NAc
      reduced laminin immunoreactivity without neuronal damage. Our findings suggest
      that the tPA-plasmin system participates in the development of behavioral
      sensitization induced by repeated METH treatment, by regulating the processes
      underlying the sensitization of METH-induced dopamine release in the NAc, in
      which degradation of laminin by plasmin may play a role.

PMID- 18036194
TI  - Modulation of dopaminergic neurotransmission in rat striatum upon in vitro and in
      vivo diclofenac treatment.
AB  - Diclofenac (DCF) is a widely used non-steroidal anti-inflammatory drug, which
      also act as a mitochondrial toxin. As it is known that selective mitochondrial
      complex I inhibition combined with mild oxidative stress causes striatal
      dopaminergic dysfunction, we tested whether DCF also compromise dopaminergic
      function in the striatum. [3H]Dopamine ([3H]DA) release was measured from rat
      striatal slices after in vitro (2 h, 10-25 micromol/L) or in vivo (3 mg/kg i.v.
      for 28 days) DCF treatment. In vitro treatment significantly decreased [3H]DA
      uptake and dopamine (DA) content of the slices. H2O2 (0.1 mmol/L)-evoked DA
      release was enhanced. Intracellular reactive oxygen species production was not
      significantly changed in the presence of DCF. After in vivo DCF treatment no
      apparent decrease in striatal DA content was observed and the uptake of [3H]DA
      into slices was increased. The intensity of tyrosine hydroxylase immunoreactivity
      in the striatum was highly variable, and both decrease and increase were observed
      in individual rats. The H2O2-evoked [3H]DA release was significantly decreased
      and the effluent contained a significant amount of [3H]octopamine, [3H]tyramine,
      and [3H]beta-phenylethylamine. The ATP content and adenylate energy charge were
      decreased. In conclusion, whereas in vitro DCF pre-treatment resembles the effect
      of the mitochondrial toxin rotenone, in vivo it rather counteracts than
      aggravates dopaminergic dysfunction.

PMID- 18036195
TI  - Gene expression profile of quinacrine-cured prion-infected mouse neuronal cells.
AB  - Prion diseases are transmissible fatal neurodegenerative diseases of humans and
      animals, characterised by the presence of an abnormal isoform (scrapie prion
      protein; PrP(Sc)) of the endogenous cellular prion protein (PrP(C)). The
      pathological mechanisms at the basis of prion diseases remain elusive, although
      the accumulation of PrP(Sc) has been linked to neurodegeneration. Different
      genomic approaches have been applied to carry out large-scale expression analysis
      in prion-infected brains and cell lines, in order to define factors potentially
      involved in pathogenesis. However, the general lack of overlap between the genes
      found in these studies prompted us to carry an analysis of gene expression using
      an alternative approach. Specifically, in order to avoid the complexities of
      shifting gene expression in a heterogeneous cell population, we used a single
      clone of GT1 cells that was de novo infected with mouse prion-infected brain
      homogenate and then treated with quinacrine to clear PrP(Sc). By comparing the
      gene expression profiles of about 15 000 genes in quinacrine-cured and not cured
      prion-infected GT1 cells, we investigated the influence of the presence or the
      absence of PrP(Sc). By real-time PCR, we confirmed that the gene encoding for
      laminin was down-regulated as a consequence of the elimination of PrP(Sc) by the
      quinacrine treatment. Thus, we speculate that this protein could be a specific
      candidate for further analysis of its role in prion infection and pathogenesis.

PMID- 18036196
TI  - The G/G genotype of a single nucleotide polymorphism at -1066 of c-Jun N-terminal
      kinase 1 gene (MAPK8) does not affect type 2 diabetes susceptibility despite the
      specific binding of AP2alpha.
AB  - OBJECTIVE: The c-Jun N-terminal kinase 1 (JNK1, mitogen-activated kinase 8;
      MAPK8) phosphorylates insulin receptor substrate-1 (IRS-1) at serine 307, which
      induces insulin resistance. MAPK8 activity is increased in obese insulin
      resistant mice, whereas mapk8 (-/-) mice show decreased adiposity and improved
      insulin sensitivity. The aim of this study was to determine the relationship
      between single nucleotide polymorphisms (SNPs) of MAPK8 and type 2 diabetes
      (T2DM). DESIGN, PATIENTS AND MEASUREMENTS: Approximately 2 kb of 5' flanking and
      the coding regions were initially sequenced in 24 Japanese T2DM subjects.
      Identified SNPs were genotyped in 204 T2DM cases and 201 nondiabetic controls.
      The function of promoter SNP-1066 (g.-1066G > A, rs10857561) was analysed by
      electrophoretic mobility shift assay (EMSA) and luciferase assay. SNP-1066 was
      further genotyped in a total of 498 cases and 407 controls, and in 2075 subjects
      in the general population. RESULTS: In 204 cases and 201 controls, 11 identified
      SNPs were not associated with T2DM. These SNPs were in the same linkage
      disequilibrium (LD) block. The tag SNP-1066 was not associated with T2DM in a
      total of 498 cases and 407 controls with the power > 80% when the relative risk
      is > 1.31. Functionally, transcription factor AP2alpha specifically recognized G
      but not A at -1066. MAPK8 promoter activity was unchanged between G and A. In
      2075 subjects, neither body mass index (BMI), fasting plasma glucose (FPG),
      homeostasis model assessment insulin resistance index (HOMA-IR), nor beta cell
      function index (HOMA-beta) was associated with SNP-1066. CONCLUSIONS: The G/G
      genotype of MAPK8 SNP-1066 did not affect T2DM susceptibility despite specific
      binding of AP2alpha.

PMID- 18036197
TI  - Regulation of the anthocyanin biosynthetic pathway by the TTG1/bHLH/Myb
      transcriptional complex in Arabidopsis seedlings.
AB  - In all higher plants studied to date, the anthocyanin pigment pathway is
      regulated by a suite of transcription factors that include Myb, bHLH and WD
      repeat proteins. However, in Arabidopsis thaliana, the Myb regulators remain to
      be conclusively identified, and little is known about anthocyanin pathway
      regulation by TTG1-dependent transcriptional complexes. Previous overexpression
      of the PAP1 Myb suggested that genes from the entire phenylpropanoid pathway are
      targets of regulation by Myb/bHLH/WD-repeat complexes in Arabidopsis, in contrast
      to other plants. Here we demonstrate that overexpression of Myb113 or Myb114
      results in substantial increases in pigment production similar to those
      previously seen as a result of over-expression of PAP1, and pigment production in
      these overexpressors remains TTG1- and bHLH-dependent. Also, plants harboring an
      RNAi construct targeting PAP1 and three Myb candidates (PAP2, Myb113 and Myb114)
      showed downregulated Myb gene expression and obvious anthocyanin deficiencies.
      Correlated with these anthocyanin deficiencies is downregulation of the same late
      anthocyanin structural genes that are downregulated in ttg1 and bHLH anthocyanin
      mutants. Expression studies using GL3:GR and TTG1:GR fusions revealed direct
      regulation of the late biosynthetic genes only. Functional diversification
      between GL3 and EGL3 with regard to activation of gene targets was revealed by
      GL3:GR studies in single and double bHLH mutant seedlings. Expression profiles
      for Myb and bHLH regulators are also presented in the context of pigment
      production in young seedlings.

PMID- 18036198
TI  - The first zygotic division in Arabidopsis requires de novo transcription of
      thymidylate kinase.
AB  - Re-activation of cell division after fertilization involves the specific
      regulation of a set of genes. To identify genes involved in the gametophytic to
      sporophytic transition, we screened Arabidopsis T-DNA insertion lines for early
      seed abortion at the zygote (zeus) or one-cell embryo stages (cyclops), and
      characterized a sporophytic zygote-lethal mutation, zeus1. ZEUS1 encodes a
      thymidylate kinase (AtTMPK) that synthesizes dTDP and is involved in the
      regulation of DNA replication. Unlike in yeast and animals, the single AtTMPK
      gene is capable of producing two proteins by alternative splicing; the longer
      isoform is targeted to the mitochondria, the shorter to the cytosol.
      Transcription of AtTMPK is activated during the G(1)/S-phase transition of the
      cell cycle, similarly to yeast and mammalian orthologues. In AtTMPK:GUS plants,
      the reporter gene was preferentially expressed in cells undergoing division, but
      was not detected during the male and female gametophytic mitoses. GUS expression
      was observed in mature embryo sacs prior to fertilization, and this expression
      may indicate the time of synchronization of the gamete cell-cycle phases.
      Identification of ZEU1 emphasizes the importance of control of the metabolism of
      DNA in the regulation of the G(1)/S-phase transition at fertilization.

PMID- 18036199
TI  - Gene trap lines identify Arabidopsis genes expressed in stomatal guard cells.
AB  - We employed a gene trap approach to identify genes expressed in stomatal guard
      cells of Arabidopsis thaliana. We examined patterns of reporter gene expression
      in approximately 20,000 gene trap lines, and recovered five lines with exclusive
      or preferential expression in stomata. The screen yielded two insertions in
      annotated genes, encoding the CYTOCHROME P450 86A2 (CYP86A2) mono-oxygenase, and
      the PLEIOTROPIC DRUG RESISTANCE 3 (AtPDR3) transporter. Expression of the trapped
      genes in guard cells was confirmed by RT-PCR experiments in purified stomata.
      Examination of homozygous mutant lines revealed that abscisic acid (ABA)-induced
      stomatal closure was impaired in the atpdr3 mutant. In three lines, insertions
      occurred outside transcribed units. Expression analysis of the genes surrounding
      the trapping inserts identified two genes selectively expressed in guard cells,
      corresponding to a PP2C PROTEIN PHOSPHATASE and an unknown expressed protein
      gene. Statistical analyses of the chromosomal regions tagged by the gene trap
      insertions revealed an over-represented [A/T]AAAG motif, previously described as
      an essential cis-active element for gene expression in stomata. The lines
      described in this work identify novel genes involved in the modulation of
      stomatal activity, provide useful markers for the study of developmental pathways
      in guard cells, and are a valuable source of guard cell-specific promoters.

PMID- 18036200
TI  - Heterologous expression, and biochemical and cellular characterization of CaPLA1
      encoding a hot pepper phospholipase A1 homolog.
AB  - Phospholipid signaling has been recently implicated in diverse cellular processes
      in higher plants. We identified a cDNA encoding the phospholipase A1 homolog
      (CaPLA1) from 5-day-old early roots of hot pepper. The deduced amino acid
      sequence showed that the lipase-specific catalytic triad is well conserved in
      CaPLA1. In vitro lipase assays and site-directed mutagenesis revealed that CaPLA1
      possesses PLA1 activity, which catalyzes the hydrolysis of phospholipids at the
      sn-1 position. CaPLA1 was selectively expressed in young roots, at days 4-5 after
      germination, and rapidly declined thereafter, suggesting that the expression of
      CaPLA1 is subject to control by a development-specific mechanism in roots.
      Because transgenic work was extremely difficult in hot peppers, in this study we
      overexpressed CaPLA1 in Arabidopsis so as to provide cellular information on the
      function of this gene. CaPLA1 overexpressors had significantly longer roots,
      leaves and petioles, and grew more rapidly than the wild-type plants, leading to
      an early bolting phenotype with prolonged inflorescence. Microscopic analysis
      showed that the vegetative tissues of 35S:CaPLA1 plants contained an increased
      number of small-sized cells, which resulted in highly populated cell layers. In
      addition, mRNAs for cell cycle-controlled proteins and fatty acid catabolizing
      enzymes were coordinately upregulated in CaPLA1-overexpressing plants. These
      results suggest that CaPLA1 is functionally relevant in heterologous Arabidopsis
      cells, and hence might participate in a subset of positive control mechanisms of
      cell and tissue growth in transgenic lines. We discuss possible biochemical and
      cellular functions of CaPLA1 in relation to the phospholipid signaling pathway in
      hot pepper and transgenic Arabidopsis plants.

PMID- 18036202
TI  - SKP2A, an F-box protein that regulates cell division, is degraded via the
      ubiquitin pathway.
AB  - Coordination between cell division and cell differentiation is crucial for growth
      and development of eukaryotic organisms. Progression through the different phases
      of cell division requires the specific degradation of proteins through the
      ubiquitin/proteasome 26S (Ub/26S) pathway. In plants, this pathway plays a key
      role in controlling several developmental processes and responses, including cell
      proliferation. SKP2A, an F-box protein, regulates the stability of the cell
      division E2FC-DPB transcription factor. Here, we show that the SKP2A forms a Skp,
      Cullin containing (SCF) complexin vivo that has E3 ubiquitin ligase activity.
      Interestingly, SKP2A is degraded through the Ub/26S pathway, and auxin regulates
      such degradation. SKP2A positively regulates cell division, at least in part by
      degrading the E2FC/DPB transcription repressor. Plants that overexpress SKP2A
      increase the number of cells in G2/M, reduce the level of ploidy and develop a
      higher number of lateral root primordia. Taken together, our results indicate
      that SKP2A is a positive regulator of cell division, and its stability is
      controlled by auxin-dependent degradation.

PMID- 18036201
TI  - An Arabidopsis homolog of the bacterial peptidoglycan synthesis enzyme MurE has
      an essential role in chloroplast development.
AB  - Enzymes encoded by bacterial MurE genes catalyze the ATP-dependent formation of
      uridine diphosphate-N-acetylmuramic acid-tripeptide in bacterial peptidoglycan
      biosynthesis. The Arabidopsis thaliana genome contains one gene with homology to
      the bacterial MurE:AtMurE. Under normal conditions AtMurE is expressed in leaves
      and flowers, but not in roots or stems. Sequence-based predictions and analyses
      of GFP fusions of the N terminus of AtMurE, as well as the full-length protein,
      suggest that AtMurE localizes to plastids. We identified three T-DNA-tagged and
      one Ds-tagged mutant alleles of AtMurE in A. thaliana. All four alleles show a
      white phenotype, and A. thaliana antisense AtMurE lines showed a pale-green
      phenotype. These results suggest that AtMurE is involved in chloroplast
      biogenesis. Cells of the mutants were inhibited in thylakoid membrane
      development. RT-PCR analysis of the mutant lines suggested that the expression of
      genes that depend on a multisubunit plastid-encoded RNA polymerase was decreased.
      To analyze the functional relationships between the MurE genes of cyanobacteria,
      the moss Physcomitrella patens and higher plants, a complementation assay was
      carried out with a P. patens (Pp) MurE knock-out line, which exhibits a small
      number of macrochloroplasts per cell. Although the Anabaena MurE, fused with the
      N-terminal region of PpMurE, complemented the macrochloroplast phenotype in P.
      patens, transformation with AtMurE did not complement this phenotype. These
      results suggest that AtMurE is functionally divergent from the bacterial and moss
      MurE proteins.

PMID- 18036203
TI  - Transient transformation and RNA silencing in Zinnia tracheary element
      differentiating cell cultures.
AB  - The Zinnia elegans cell culture system is a robust and physiologically relevant
      in vitro system for the study of xylem formation. Freshly isolated mesophyll
      cells of Zinnia can be hormonally induced to semisynchronously transdifferentiate
      into tracheary elements (TEs). Although the system has proven to be valuable, its
      utility is diminished by the lack of an efficient transformation protocol. We
      herein present a novel method to introduce DNA/RNA efficiently into Zinnia cells
      by electroporation-based transient transformation. Using reporter gene plasmids,
      we optimized the system for efficiency of transformation and ability for the
      transformed cells to transdifferentiate into TEs. Optimal conditions included a
      partial digestion of the cell walls by pectolyase, a low voltage and high
      capacitance electrical pulse and an optimal medium to maintain cell viability
      during transformation. Beyond the simple expression of a reporter protein in
      Zinnia cells, we extended our protocol to subcellular protein targeting,
      simultaneous co-expression of several reporter proteins and promoter-activity
      monitoring during TE differentiation. Most importantly, we tested the system for
      double-stranded RNA (dsRNA)-induced RNA silencing. By introducing in vitro
      synthesized dsRNAs, we were able to phenocopy the Arabidopsis cellulose synthase
      (CesA) mutants that had defects in secondary cell-wall synthesis. Suppressing the
      expression ofZinnia CesA homologues resulted in an increase of abnormal TEs with
      aberrant secondary walls. Our electroporation-based transient transformation
      protocol provides the suite of tools long required for functional analysis and
      developmental studies at single cell levels.

PMID- 18036204
TI  - Chlamydomonas chloroplasts can use short dispersed repeats and multiple pathways
      to repair a double-strand break in the genome.
AB  - Certain group I introns insert into intronless DNA via an endonuclease that
      creates a double-strand break (DSB). There are two models for intron homing in
      phage: synthesis-dependent strand annealing (SDSA) and double-strand break repair
      (DSBR). The Cr.psbA4 intron homes efficiently from a plasmid into the chloroplast
      psbA gene in Chlamydomonas, but little is known about the mechanism. Analysis of
      co-transformants selected using a spectinomycin-resistant 16S gene (16S(spec))
      provided evidence for both pathways. We also examined the consequences of the
      donor DNA having only one-sided or no homology with the psbA gene. When there was
      no homology with the donor DNA, deletions of up to 5 kb involving direct repeats
      that flank the psbA gene were obtained. Remarkably, repeats as short as 15 bp
      were used for this repair, which is consistent with the single-strand annealing
      (SSA) pathway. When the donor had one-sided homology, the DSB in most co
      transformants was repaired using two DNAs, the donor and the 16S(spec) plasmid,
      which, coincidentally, contained a region that is repeated upstream of psbA. DSB
      repair using two separate DNAs provides further evidence for the SDSA pathway.
      These data show that the chloroplast can repair a DSB using short dispersed
      repeats located proximally, distally, or even on separate molecules relative to
      the DSB. They also provide a rationale for the extensive repertoire of repeated
      sequences in this genome.

PMID- 18036205
TI  - ROXY1 and ROXY2, two Arabidopsis glutaredoxin genes, are required for anther
      development.
AB  - Glutaredoxins (GRXs) are small oxidoreductases that are involved in various
      cellular processes and play a crucial role in responses to oxidative stress.
      Three GRX subgroups exist in plants, and GRXs with active sites of the CPYC and
      CGFS types are common to pro- and eukaryotes. In contrast, GRXs with the CC type
      motif have so far only been identified in land plants. Here, we report that the
      two CC-type GRXs ROXY1 and ROXY2 together control anther development in
      Arabidopsis thaliana. Single roxy1 and roxy2 mutants are fertile and produce
      normal anthers. However, roxy1 roxy2 double mutants are sterile and do not
      produce pollen. Strikingly, abaxial and adaxial anther lobe differentiation are
      differently affected, with early lobe differentiation being defective in the
      adaxial lobes, whereas later steps during pollen mother cell differentiation are
      disrupted in the abaxial lobes. Expression studies show that ROXY1 and ROXY2 are
      expressed with overlapping patterns during anther development. Lack of ROXY1 and
      ROXY2 function affects a large number of anther genes at the transcriptional
      level. Genetic and RT-PCR data imply that ROXY1/2 function downstream of the
      early-acting anther gene SPOROCYTELESS/NOZZLE and upstream of DYSFUNCTIONAL
      TAPETUM1, controlling tapetum development. Mutagenesis of a conserved glutathione
      binding glycine in the ROXY1 protein indicates that CC-type GRXs need to interact
      with glutathione to catalyze essential biosynthetic reactions. Analysis of these
      two novel anther genes indicates that redox regulation, as well as participating
      in plant stress defense mechanisms, might play a major role in the control of
      male gametogenesis.

PMID- 18036206
TI  - Role of a GDSL lipase-like protein as sinapine esterase in Brassicaceae.
AB  - The seeds of most members of the Brassicaceae accumulate high amounts of sinapine
      (sinapoylcholine) that is rapidly hydrolyzed during early stages of seed
      germination. One of three isoforms of sinapine esterase activity (BnSCE3) has
      been isolated from Brassica napus seedlings and subjected to trypsin digestion
      and spectrometric sequencing. The peptide sequences were used to isolate BnSCE3
      cDNA, which was shown to contain an open reading frame of 1170 bp encoding a
      protein of 389 amino acids, including a leader peptide of 25 amino acids.
      Sequence comparison identified the protein as the recently cloned BnLIP2, i.e. a
      GDSL lipase-like protein, which displays high sequence identity to a large number
      of corresponding plant proteins, including four related Arabidopsis lipases. The
      enzymes belong to the SGNH protein family, which use a catalytic triad of Ser-Asp
      His, with serine as the nucleophile of the GDSL motif. The corresponding B. napus
      and Arabidopsis genes were heterologously expressed in Nicotiana benthamiana
      leaves and proved to confer sinapine esterase activity. In addition to sinapine
      esterase activity, the native B. napus protein (BnSCE3/BnLIP2) showed broad
      substrate specificity towards various other choline esters, including
      phosphatidylcholine. This exceptionally broad substrate specificity, which is
      common to a large number of other GDSL lipases in plants, hampers their
      functional analysis. However, the data presented here indicate a role for the
      GDSL lipase-like BnSCE3/BnLIP2 as a sinapine esterase in members of the
      Brassicaceae, catalyzing hydrolysis of sinapine during seed germination, leading,
      via 1-O-sinapoyl-beta-glucose, to sinapoyl-l-malate in the seedlings.

PMID- 18036207
TI  - Personality, psychological stress, and self-reported influenza symptomatology.
AB  - BACKGROUND: Psychological stress and negative mood have been related to increased
      vulnerability to influenza-like illness (ILI). This prospective study re
      evaluated the predictive value of perceived stress for self-reported ILI. We
      additionally explored the role of the negative affectivity and social inhibition
      traits. METHODS: In this study, 5,404 respondents from the general population
      were assessed in terms of perceived stress, personality, and control variables
      (vaccination, vitamin use, exercise, etc.). ILI were registered weekly using self
      report measures during a follow-up period of four weeks. RESULTS: Multivariable
      logistic regression analysis on ILI was performed to test the predictive power of
      stress and personality. In this model, negative affectivity (OR = 1.05, p =
      0.009), social inhibition (OR = 0.97, p = 0.011), and perceived stress (OR =
      1.03, p = 0.048) predicted ILI reporting. Having a history of asthma (OR = 2.33,
      p = < 0.0001) was also associated with ILI reporting. Older age was associated
      with less self-reported ILI (OR = 0.98, P = 0.017). CONCLUSION: Elderly and
      socially inhibited persons tend to report less ILI as compared to their younger
      and less socially inhibited counterparts. In contrast, asthma, trait negative
      affectivity, and perceived stress were associated with higher self-report of ILI.
      Our results demonstrate the importance of including trait markers in future
      studies examining the relation between stress and self-report symptom measures.

PMID- 18036208
TI  - Prevalence of H63D, S65C and C282Y hereditary hemochromatosis gene mutations in
      Slovenian population by an improved high-throughput genotyping assay.
AB  - BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease
      characterized by excessive iron overload that leads to multi-organ failure.
      Although the most prevalent genotype in HH is homozygosity for C282Y mutation of
      the HFE gene, two additional mutations, H63D and S65C, appear to be associated
      with a milder form of HH. The aim of this study was to develop a high-throughput
      assay for HFE mutations screening based on TaqMan technology and to determine the
      frequencies of HFE mutations in the Slovenian population. METHODS: Altogether,
      1282 randomly selected blood donors from different Slovenian regions and 21 HH
      patients were analyzed for the presence of HFE mutations by an in-house developed
      real-time PCR assay based on TaqMan technology using shorter non-interfering
      fluorescent single nucleotide polymorphism (SNP)-specific MGB probes. The assay
      was validated by RFLP analysis and DNA sequencing. RESULTS: The genotyping assay
      of the H63D, S65C and C282Y mutations in the HFE gene, based on TaqMan technology
      proved to be fast, reliable, with a high-throughput capability and 100%
      concordant with genotypes obtained by RFLP and DNA sequencing. The observed
      frequency of C282Y homozygotes in the group of HH patients was only 48%, others
      were of the heterogeneous HFE genotype. Among 1282 blood donors tested, the
      observed H63D, S65C and C282Y allele frequency were 12.8% (95% confidence
      interval (CI) 11.5-14.2%), 1.8% (95% CI 1.4-2.5%) and 3.6% (95% CI 3.0-4.5%),
      respectively. Approximately 33% of the tested subjects had at least one of the
      three HH mutations, and 1% of them were C282Y homozygotes or compound
      heterozygotes C282Y/H63D or C282Y/S65C, presenting an increased risk for iron
      overload disease. A significant variation in H63D allele frequency was observed
      for one of the Slovenian regions. CONCLUSION: The improved real-time PCR assay
      for H63D, S65C and C282Y mutations detection is accurate, fast, cost-efficient
      and ready for routine screening and diagnostic procedures. The genotype
      frequencies in the Slovenian population agree with those reported for the Central
      European populations although some deviations where observed in comparison with
      other populations of Slavic origin. Regional distribution of the mutations should
      be considered when planning population screening.

PMID- 18036210
TI  - Health-related quality of life and migration: a cross-sectional study on elderly
      Iranians in Sweden.
AB  - BACKGROUND: Although elderly Iranian immigrants in Sweden are the largest elderly
      group born outside Europe, little is known about their health-related quality of
      life (HRQL). The aim of this study was to examine the association between
      migration status and HRQL in a comparison of elderly Iranians in Iran, elderly
      Iranian immigrants in Sweden, and elderly Swedes in Sweden. METHODS: The Short
      Form Health Survey (SF-36) was administered to a total of 625 men and women aged
      60-84 years to collect HRQL information on elderly Iranians in Sweden (n = 176)
      and elderly Iranians in Iran (n = 298). A Swedish control group (n = 151) was
      also randomly selected from the general population. Multiple linear regression
      procedures were applied to analyze data while adjusting for age, which was
      categorized into 60-69, and 70-84 years, and education. RESULTS: Iranian women in
      Sweden with shorter times of residence scored lower on vitality (beta-coefficient
      = -7.9, 95% CI = -14.3 to -1.5) compared with other women in this study. The
      lower vitality dimension score remained nearly unchanged in the main model (beta
      coefficient = -7.3, 95% CI = -13.7 to -0.9). A longer period of residence in
      Sweden had a positive association with social functioning (beta-coefficient =
      14.1, 95% CI = 3.1-25.1) and role limitation due to emotional problems (beta
      coefficient = 18.3, 95% CI = 1.4-35.2) among elderly Iranian women. In general,
      the Swedish subsample scores higher on all dimensions of the SF-36 among women
      and in six out of eight among men in relation to the rest of the subsamples.
      CONCLUSION: The HRQL of elderly Iranians in Sweden was more like that of their
      countrymen in Iran than that of Swedes, who reported a better HRQL than Iranians
      in this study. However, length of time since migration to Sweden is not
      associated with poorer HRQL among elderly Iranians. The association varied,
      however, with sex. Elderly Iranian women showed an increase in two of eight
      dimensions of the SF-36 with additional years in Sweden, whereas, among elderly
      Iranian men, additional years in Sweden were not associated with HRQL.

PMID- 18036209
TI  - Gene array identification of Ipf1/Pdx1-/- regulated genes in pancreatic
      progenitor cells.
AB  - BACKGROUND: The homeodomain transcription factor IPF1/PDX1 exerts a dual role in
      the pancreas; Ipf1/Pdx1 global null mutants fail to develop a pancreas whereas
      conditional inactivation of Ipf1/Pdx1 in beta-cells leads to impaired beta-cell
      function and diabetes. Although several putative target genes have been linked to
      the beta-cell function of Ipf1/Pdx1, relatively little is known with respect to
      genes regulated by IPF1/PDX1 in early pancreatic progenitor cells. RESULTS:
      Microarray analyses identified a total of 111 genes that were differentially
      expressed in e10.5 pancreatic buds of Ipf1/Pdx1-/- embryos. The expression of one
      of these, Spondin 1, which encodes an extracellular matrix protein, has not
      previously been described in the pancreas. Quantitative real-time RT-PCR analyses
      and immunohistochemical analyses also revealed that the expression of FgfR2IIIb,
      that encodes the receptor for FGF10, was down-regulated in Ipf1/Pdx1-/-
      pancreatic progenitor cells. CONCLUSION: This microarray analysis has identified
      a number of candidate genes that are differentially expressed in Ipf1/Pdx1-/-
      pancreatic buds. Several of the differentially expressed genes were known to be
      important for pancreatic progenitor cell proliferation and differentiation
      whereas others have not previously been associated with pancreatic development.

PMID- 18036211
TI  - Family structure and health, how companionship acts as a buffer against ill
      health.
AB  - BACKGROUND: Health and well-being are the result of synergistic interactions
      among a variety of determinants. Family structure and composition are social
      determinants that may also affect health behaviours and outcomes. This study was
      performed to examine the associations between family structure and health and to
      determine the protective effects of support mechanisms to improve quality of
      health outcome. METHODS: Six hundred people, selected by multistage sampling to
      obtain a representative population of men and women aged 20-60 living in
      communities in Japan, were included in this study. Data regarding subjective
      views of one's own health, family structure, lifestyle and social support were
      collected through structured face-to-face interviews on home visits. Systolic and
      diastolic blood pressures, height and weight were measured by trained examiners.
      The associations between family structure and health after controlling for
      demographics, lifestyle and social support were examined using logistic and
      linear regression analyses. RESULTS: Subjects living alone were significantly
      more likely to be in ill health, as determined using the General Health
      Questionnaire, in comparison to those in extended families (OR = 3.14). Subjects
      living alone or as couples were significantly more likely to suffer from severe
      hypertension in comparison to those living in extended families (OR = 8.25, OR =
      4.90). These associations remained after controlling for the influence of
      lifestyle. Subjects living only with spouse or in nuclear family had higher
      probabilities of mental ill health in the absence than in the presence of people
      showing concern for their well-being. CONCLUSION: The results of this study
      infers that a support mechanism consisting of companionship and the presence of
      family or other people concerned for one's well being acts as a buffer against
      deleterious influence of living in small family that will lead to improved
      quality of health outcome.

PMID- 18036213
TI  - Psychosocial and treatment correlates of opiate free success in a clinical review
      of a naltrexone implant program.
AB  - BACKGROUND: There is on-going controversy in relation to the efficacy of
      naltrexone used for the treatment of heroin addiction, and the important
      covariates of that success. We were also interested to review our experience with
      two depot forms of implantable naltrexone. METHODS: A retrospective review of
      patients' charts was undertaken, patients were recalled by telephone and by
      letter, and urine drug screen samples were collected. Opiate free success (OFS)
      was the parameter of interest. Three groups were defined. The first two were
      treated in the previous 12 months and comprised "implant" and "tablet" patients.
      A third group was "historical" comprising those treated orally in the preceding
      12 months. RESULTS: There were 102, 113 and 161 patients in each group
      respectively. Groups were matched for age, sex, and dose of heroin used, but not
      financial status or social support. The overall follow-up rate was 82%. The
      Kaplan Meier 12 month OFS were 82%, 58% and 52% respectively. 12 post-treatment
      variables were independently associated with treatment retention. In a Cox
      proportional hazard multivariate model social support, the number of
      detoxification episodes, post-treatment employment, the use of multiple implant
      episodes and spiritual belief were significantly related to OFS. CONCLUSION:
      Consistent with the voluminous international literature clinically useful
      retention rates can be achieved with naltrexone, which may be improved by
      implants and particularly serial implants, repeat detoxification, meticulous
      clinical follow-up, and social support. As depot formulations of naltrexone
      become increasingly available such results can guide their clinical deployment,
      improve treatment outcomes, and enlarge the policy options for an exciting non
      addictive pharmacotherapy for opiate addiction.

PMID- 18036212
TI  - Expression profiling on soybean leaves reveals integration of ER- and osmotic
      stress pathways.
AB  - BACKGROUND: Despite the potential of the endoplasmic reticulum (ER) stress
      response to accommodate adaptive pathways, its integration with other
      environmental-induced responses is poorly understood in plants. We have
      previously demonstrated that the ER-stress sensor binding protein (BiP) from
      soybean exhibits an unusual response to drought. The members of the soybean BiP
      gene family are differentially regulated by osmotic stress and soybean BiP
      confers tolerance to drought. While these results may reflect crosstalk between
      the osmotic and ER-stress signaling pathways, the lack of mutants,
      transcriptional response profiles to stresses and genome sequence information of
      this relevant crop has limited our attempts to identify integrated networks
      between osmotic and ER stress-induced adaptive responses. As a fundamental step
      towards this goal, we performed global expression profiling on soybean leaves
      exposed to polyethylene glycol treatment (osmotic stress) or to ER stress
      inducers. RESULTS: The up-regulated stress-specific changes unmasked the major
      branches of the ER-stress response, which include enhancing protein folding and
      degradation in the ER, as well as specific osmotically regulated changes linked
      to cellular responses induced by dehydration. However, a small proportion (5.5%)
      of total up-regulated genes represented a shared response that seemed to
      integrate the two signaling pathways. These co-regulated genes were considered
      downstream targets based on similar induction kinetics and a synergistic response
      to the combination of osmotic- and ER-stress-inducing treatments. Genes in this
      integrated pathway with the strongest synergistic induction encoded proteins with
      diverse roles, such as plant-specific development and cell death (DCD) domain
      containing proteins, an ubiquitin-associated (UBA) protein homolog and NAC domain
      containing proteins. This integrated pathway diverged further from characterized
      specific branches of ER-stress as downstream targets were inversely regulated by
      osmotic stress. CONCLUSION: The present ER-stress- and osmotic-stress-induced
      transcriptional studies demonstrate a clear predominance of stimulus-specific
      positive changes over shared responses on soybean leaves. This scenario indicates
      that polyethylene glycol (PEG)-induced cellular dehydration and ER stress
      elicited very different up-regulated responses within a 10-h stress treatment
      regime. In addition to identifying ER-stress and osmotic-stress-specific
      responses in soybean (Glycine max), our global expression-profiling analyses
      provided a list of candidate regulatory components, which may integrate the
      osmotic-stress and ER-stress signaling pathways in plants.

PMID- 18036214
TI  - Evolutionary consequences of a large duplication event in Trypanosoma brucei:
      chromosomes 4 and 8 are partial duplicons.
AB  - BACKGROUND: Gene order along the genome sequence of the human parasite
      Trypanosoma brucei provides evidence for a 0.5 Mb duplication, comprising the 3'
      regions of chromosomes 4 and 8. Here, the principal aim was to examine the
      contribution made by this duplication event to the T. brucei genome sequence,
      emphasising the consequences for gene content and the evolutionary change
      subsequently experienced by paralogous gene copies. The duplicated region may be
      browsed online at http://www.genedb.org/genedb/tryp/48dup_image.jsp RESULTS:
      Comparisons of trypanosomatid genomes demonstrated widespread gene loss from each
      duplicon, but also showed that 47% of duplicated genes were retained on both
      chromosomes as paralogous loci. Secreted and surface-expressed genes were over
      represented among retained paralogs, reflecting a bias towards important factors
      at the host-parasite interface, and consistent with a dosage-balance hypothesis.
      Genetic divergence in both coding and regulatory regions of retained paralogs was
      bimodal, with a deficit in moderately divergent paralogs; in particular, non
      coding sequences were either conserved or entirely remodelled. The conserved
      paralogs included examples of remarkable sequence conservation, but also
      considerable divergence of both coding and regulatory regions. Sequence
      divergence typically displayed strong negative selection; but several features,
      such as asymmetric evolutionary rates, positively-selected codons and other non
      neutral substitutions, suggested that divergence of some paralogs was driven by
      functional change. The absence of orthologs to retained paralogs in T. congolense
      indicated that the duplication event was specific to T. brucei. CONCLUSION: The
      duplication of this chromosomal region doubled the dosage of many genes. Rather
      than creating 'more of the same', these results show that paralogs were
      structurally modified according to various evolutionary trajectories. The
      retention of paralogs, and subsequent elaboration of both their primary
      structures and regulatory regions, strongly suggests that this duplication was a
      seminal development, stimulating functional innovation and fundamentally altering
      the genetic repertoire of T. brucei relative to other trypanosomatids.

PMID- 18036215
TI  - Comparison of international guideline programs to evaluate and update the Dutch
      program for clinical guideline development in physical therapy.
AB  - BACKGROUND: Clinical guidelines are considered important instruments to improve
      quality in health care. Since 1998 the Royal Dutch Society for Physical Therapy
      (KNGF) produced evidence-based clinical guidelines, based on a standardized
      program. New developments in the field of guideline research raised the need to
      evaluate and update the KNGF guideline program. Purpose of this study is to
      compare different guideline development programs and review the KNGF guideline
      program for physical therapy in the Netherlands, in order to update the program.
      METHOD: Six international guideline development programs were selected, and the
      23 criteria of the AGREE Instrument were used to evaluate the guideline programs.
      Information about the programs was retrieved from published handbooks of the
      organizations. Also, the Dutch program for guideline development in physical
      therapy was evaluated using the AGREE criteria. Further comparison the six
      guideline programs was carried out using the following elements of the guideline
      development processes: Structure and organization; Preparation and initiation;
      Development; Validation; Dissemination and implementation; Evaluation and update.
      RESULTS: Compliance with the AGREE criteria of the guideline programs was high.
      Four programs addressed 22 AGREE criteria, and two programs addressed 20 AGREE
      criteria. The previous Dutch program for guideline development in physical
      therapy lacked in compliance with the AGREE criteria, meeting only 13 criteria.
      Further comparison showed that all guideline programs perform systematic
      literature searches to identify the available evidence. Recommendations are
      formulated and graded, based on evidence and other relevant factors. It is not
      clear how decisions in the development process are made. In particular, the
      process of translating evidence into practice recommendations can be improved.
      CONCLUSION: As a result of international developments and consensus, the
      described processes for developing clinical practice guidelines have much in
      common. The AGREE criteria are common basis for the development of guidelines,
      although it is not clear how final decisions are made. Detailed comparison of the
      different guideline programs was used for updating the Dutch program. As a result
      the updated KNGF program complied with 22 AGREE criteria. International
      discussion is continuing and will be used for further improvement of the program.

PMID- 18036217
TI  - What is an acceptably smoothed fluence? Dosimetric and delivery considerations
      for dynamic sliding window IMRT.
AB  - BACKGROUND: The study summarised in this report aimed to investigate the
      interplay between fluence complexity, dose calculation algorithms, dose
      calculation spatial resolution and delivery characteristics (monitor units,
      effective field width and dose delivery against dose prediction agreement) was
      investigated. A sample set of complex planning cases was selected and tested
      using a commercial treatment planning system capable of inverse optimisation and
      equipped with tools to tune fluence smoothness. METHODS: A set of increasingly
      smoothed fluence patterns was correlated to a generalised expression of the
      Modulation Index (MI) concept, in nature independent from the specific planning
      system used that could therefore be recommended as a predictor to score fluence
      "quality" at a very early stage of the IMRT QA process. Fluence complexity was
      also correlated to delivery accuracy and characteristics in terms of number of
      MU, dynamic window width and agreement between calculation and measurement
      (expressed as percentage of field area with a gamma > 1 (%FA)) when comparing
      calculated vs. delivered modulated dose maps. Different resolutions of the
      calculation grid and different photon dose algorithms (pencil beam and
      anisotropic analytical algorithm) were used for the investigations. RESULTS AND
      CONCLUSION: i) MI can be used as a reliable parameter to test different
      approaches/algorithms to smooth fluences implemented in a TPS, and to identify
      the preferable default values for the smoothing parameters if appropriate tools
      are implemented; ii) a MI threshold set at MI < 19 could ensure that the planned
      beams are safely and accurately delivered within stringent quality criteria; iii)
      a reduction in fluence complexity is strictly correlated to a corresponding
      reduction in MUs, as well as to a decrease of the average sliding window width
      (for dynamic IMRT delivery); iv) a smoother fluence results in a reduction of
      dose in the healthy tissue with a potentially relevant clinical benefit; v)
      increasing the smoothing parameter s, MI decreases with %FA: fluence complexity
      has a significant impact on the accuracy of delivery and the agreement between
      calculation and measurements improves with the advanced algorithms.

PMID- 18036216
TI  - Relationship between pp65 antigenemia levels and real-time quantitative DNA PCR
      for Human Cytomegalovirus (HCMV) management in immunocompromised patients.
AB  - BACKGROUND: Quantitative real-time PCR assays, which are more rapid and practical
      than pp65 antigenemia determination, are progressively becoming the preferred
      method for monitoring Human Cytomegalovirus (HCMV) reactivation. However, the
      relationship between HCMV DNA and antigenemia levels is still under
      investigation. The aim of this study was to analyse the relationship between HCMV
      DNA and pp65 antigenemia levels in order to identify clinically useful threshold
      values for the management of patients. METHODS: 475 consecutive samples from 156
      immunosuppressed patients were tested for HCMV by pp65 antigenemia and Real-time
      PCR assay. RESULTS: 136 out of 475 consecutive samples derived from 48 patients
      showed evidence of HCMV infection. HCMV DNA was detected in 106 samples, pp65
      antigen in 3, and both markers in 27. pp65 antigen detection was associated with
      higher HCMV DNA levels. The cut-off HCMV DNA level that best predicted pp65
      antigenemia in this series of samples was 11,500 copies/ml, but different
      threshold levels could be observed for specific groups of patients. HCMV disease
      was observed in 5 out of 48 patients with active HCMV infection. The presence of
      clinical symptoms was associated with positive pp65 and with higher antigenemia
      levels. Higher HCMV DNA load at the onset of viral replication was correlated to
      the development of clinical symptoms. CONCLUSION: Both pp65 antigenemia and HCMV
      DNA load can be useful for the prospective monitoring of immunocompromised
      subjects. Specific cut-off levels capable of triggering preemptive antiviral
      treatment should be determined in accordance to the type of test used and the
      characteristics of patients and prospectively validated.

PMID- 18036218
TI  - Brucella bacteremia in patients with acute leukemia: a case series.
AB  - BACKGROUND: Brucellosis may cause serious infections in healthy individuals
      living in countries that are endemic for the infection. However, reports of
      brucella infections in immunocompromised hosts are relatively rare. CASE
      PRESENTATIONS: Reported here are two patients with acute leukemia who developed
      Brucella melitensis bacteremia during their follow up at the Armed Forces
      Hospital in Riyadh. The first patient developed B. melitensis bacteremia during
      the transformation of his myelodysplasia into acute myeloid leukemia. The second
      patient developed B. melitensis bacteremia while his acute lymphoblastic leukemia
      was under control. Interestingly, he presented with acute cholecystitis during
      the brucella sepsis. Both brucella infections were associated with a marked
      reduction in the hematological parameters in addition to other complications. The
      bacteremic episodes were successfully treated with netilmicin, doxycycline and
      ciprofloxacin. CONCLUSION: Brucellosis can cause systemic infections, complicated
      bacteremia and serious morbidity in patients with acute leukemia living in
      endemic areas. These infections may occur at the presentation of the leukemia or
      even when the leukemia is in remission. Nevertheless, the early diagnosis of
      brucellosis and the administration of appropriate antimicrobial therapy for
      sufficient duration usually improves the outcome in these immunocompromised
      patients.

PMID- 18036219
TI  - An accurate method for quantifying and analyzing copy number variation in porcine
      KIT by an oligonucleotide ligation assay.
AB  - BACKGROUND: Aside from single nucleotide polymorphisms, copy number variations
      (CNVs) are the most important factors in susceptibility to genetic disorders
      because they affect expression levels of genes. In previous studies,
      pyrosequencing, mini-sequencing, real-time PCR, invader assays and other
      techniques have been used to detect CNVs. However, the higher the copy number in
      a genome, the more difficult it is to resolve the copies, so a more accurate
      method for measuring CNVs and assigning genotype is needed. RESULTS: PCR followed
      by a quantitative oligonucleotide ligation assay (qOLA) was developed for
      quantifying CNVs. The accuracy and precision of the assay were evaluated for
      porcine KIT, which was selected as a model locus. Overall, the root mean squares
      of bias and standard deviation of qOLA were 2.09 and 0.45, respectively. These
      values are less than half of those in the published pyrosequencing assay for
      analyzing CNV in porcine KIT. Using a combined method of qOLA and another
      pyrosequencing for quantitative analysis of KIT copies with spliced forms, we
      confirmed the segregation of KIT alleles in 145 F1 animals with pedigree
      information and verified the correct assignment of genotypes. In a diagnostic
      test on 100 randomly sampled commercial pigs, there was perfect agreement between
      the genotypes obtained by grouping observations on a scatter plot and by
      clustering using the nearest centroid sorting method implemented in PROC FASTCLUS
      of the SAS package. In a test on 159 Large White pigs, there were only two
      discrepancies between genotypes assigned by the two clustering methods (98.7%
      agreement), confirming that the quantitative ligation assay established here
      makes genotyping possible through the accurate measurement of high KIT copy
      numbers (>4 per diploid genome). Moreover, the assay is sensitive enough for use
      on DNA from hair follicles, indicating that DNA from various sources could be
      used. CONCLUSION: We have established a high resolution quantification method
      using an oligonucleotide ligation assay to measure CNVs, and verified the
      reliability of genotype assignment for random animal samples using the nearest
      centroid sorting method. This new method will make it more practical to determine
      KIT CNV and to genotype the complicated Dominant White/KIT locus in pigs. This
      procedure could have wide applications for studying gene or segment CNVs in other
      species.

PMID- 18036220
TI  - Effect of pre-germinated brown rice intake on diabetic neuropathy in
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND: To study the effects of a pre-germinated brown rice diet (PR) on
      diabetic neuropathy in streptozotocin (STZ)-induced diabetic rats. METHODS: The
      effects of a PR diet on diabetic neuropathy in STZ-induced diabetic rats were
      evaluated and compared with those fed brown rice (BR) or white rice (WR) diets
      with respect to the following parameters: blood-glucose level, motor-nerve
      conduction velocity (NCV), sciatic-nerve Na+/K+-ATPase activity, and serum
      homocysteine-thiolactonase (HTase) activity. RESULTS: Compared with diabetic rats
      fed BR or WR diets, those fed a PR diet demonstrated significantly lower blood
      glucose levels (p < 0.001), improved NCV (1.2- and 1.3-fold higher,
      respectively), and increased Na+/K+-ATPase activity (1.6- and 1.7-fold higher,
      respectively). The PR diet was also able to normalize decreased serum
      homocysteine levels normally seen in diabetic rats. The increased Na+/K+-ATPase
      activity observed in rats fed PR diets was associated with elevations in HTase
      activity (r = 0.913, p < 0.001). The in vitro effect of the total lipid extract
      from PR bran (TLp) on the Na+/K+-ATPase and HTase activity was also examined.
      Incubation of homocysteine thiolactone (HT) with low-density lipoprotein (LDL) in
      vitro resulted in generation of HT-modified LDL, which possessed high potency to
      inhibit Na+/K+-ATPase activity in the sciatic nerve membrane. The inhibitory
      effect of HT-modified LDL on Na+/K+-ATPase activity disappeared when TLp was
      added to the incubation mixture. Furthermore, TLp directly activated the HTase
      associated with high-density lipoprotein (HDL). CONCLUSION: PR treatment shows
      efficacy for protecting diabetic deterioration and for improving physiological
      parameters of diabetic neuropathy in rats, as compared with a BR or WR diet. This
      effect may be induced by a mechanism whereby PR intake mitigates diabetic
      neuropathy by one or more factors in the total lipid fraction. The active lipid
      fraction is able to protect the Na+/K+-ATPase of the sciatic-nerve membrane from
      the toxicity of HT-modified LDL and to directly activate the HTase of HDL.

PMID- 18036221
TI  - Creating a medical dictionary using word alignment: the influence of sources and
      resources.
AB  - BACKGROUND: Automatic word alignment of parallel texts with the same content in
      different languages is among other things used to generate dictionaries for new
      translations. The quality of the generated word alignment depends on the quality
      of the input resources. In this paper we report on automatic word alignment of
      the English and Swedish versions of the medical terminology systems ICD-10, ICF,
      NCSP, KSH97-P and parts of MeSH and how the terminology systems and type of
      resources influence the quality. METHODS: We automatically word aligned the
      terminology systems using static resources, like dictionaries, statistical
      resources, like statistically derived dictionaries, and training resources, which
      were generated from manual word alignment. We varied which part of the
      terminology systems that we used to generate the resources, which parts that we
      word aligned and which types of resources we used in the alignment process to
      explore the influence the different terminology systems and resources have on the
      recall and precision. After the analysis, we used the best configuration of the
      automatic word alignment for generation of candidate term pairs. We then manually
      verified the candidate term pairs and included the correct pairs in an English
      Swedish dictionary. RESULTS: The results indicate that more resources and
      resource types give better results but the size of the parts used to generate the
      resources only partly affects the quality. The most generally useful resources
      were generated from ICD-10 and resources generated from MeSH were not as general
      as other resources. Systematic inter-language differences in the structure of the
      terminology system rubrics make the rubrics harder to align. Manually created
      training resources give nearly as good results as a union of static resources,
      statistical resources and training resources and noticeably better results than a
      union of static resources and statistical resources. The verified English-Swedish
      dictionary contains 24,000 term pairs in base forms. CONCLUSION: More resources
      give better results in the automatic word alignment, but some resources only give
      small improvements. The most important type of resource is training and the most
      general resources were generated from ICD-10.

PMID- 18036222
TI  - Multiple jejuno-jejunal fistulae of uncertain origin: a case report.
AB  - A 43 year-old male patient presented with small bowel obstruction while being
      treated for cervical tuberculous lymphadenopathy. Laparotomy revealed multiple
      adhesions and multiple jejuno-jejunal fistulae. Absence of previous abdominal
      surgery or other abdominal insult favoured an 'idiopathic' origin of these
      unusual lesions, although treated tuberculosis may have been the underlying
      cause. To the best of our knowledge this intestinal condition has never
      previously been reported in the medical literature.

PMID- 18036223
TI  - Compatible solutes from hyperthermophiles improve the quality of DNA microarrays.
AB  - BACKGROUND: DNA microarrays are among the most widely used technical platforms
      for DNA and RNA studies, and issues related to microarrays sensitivity and
      specificity are therefore of general importance in life sciences. Compatible
      solutes are derived from hyperthermophilic microorganisms and allow such
      microorganisms to survive in environmental and stressful conditions. Compatible
      solutes show stabilization effects towards biological macromolecules, including
      DNA. RESULTS: We report here that compatible solutes from hyperthermophiles
      increased the performance of the hybridization buffer for Affymetrix GeneChip(R)
      arrays. The experimental setup included independent hybridizations with constant
      RNA over a wide range of compatible solute concentrations. The dependence of
      array quality and compatible solute was assessed using specialized statistical
      tools provided by both the proprietary Affymetrix quality control system and the
      open source Bioconductor suite. CONCLUSION: Low concentration (10 to 25 mM) of
      hydroxyectoine, potassium mannosylglycerate and potassium diglycerol phosphate in
      hybridization buffer positively affected hybridization parameters and enhanced
      microarrays outcome. This finding harbours a strong potential for the improvement
      of DNA microarray experiments.

PMID- 18036225
TI  - Widening access to cardiovascular healthcare: community screening among ethnic
      minorities in inner-city Britain - the Healthy Hearts Project.
AB  - BACKGROUND: The burden of cardiovascular disease (CVD) in Britain is concentrated
      in inner-city areas such as Sandwell, which is home to a diverse multi-ethnic
      population. Current guidance for CVD risk screening is not established, nor are
      there specific details for ethnic minorities. Given the disparity in equitable
      healthcare for these groups, we developed a 'tailored' and systematic approach to
      CVD risk screening within communities of the Sandwell locality. The key
      anticipated outcomes were the numbers of participants from various ethnic
      backgrounds attending the health screening events and the prevalence of known and
      undiagnosed CVD risk within ethnic groups. METHODS: Data was collected during 10
      health screening events (September 2005 and July 2006), which included an
      assessment of raised blood pressure, overweight, hyperlipidaemia, impaired
      fasting glucose, smoking habit and the 10 year CVD risk score. Specific features
      of our approach included (i) community involvement, (ii) a clinician who could
      deliver immediate attention to adverse findings, and (iii) the use of an
      interpreter. RESULTS: A total of 824 people from the Sandwell were included in
      this study (47% men, mean age 47.7 years) from community groups such as the
      Gujarati Indian, Punjabi Indian, European Caucasian, Yemeni, Pakistani and
      Bangladeshi. A total of 470 (57%) individuals were referred to their General
      Practitioner with a report of an increased CVD score - undetected high blood
      pressure in 120 (15%), undetected abnormal blood glucose in 70 (8%), undetected
      raised total cholesterol in 149 (18%), and CVD risk management review in 131
      (16%). CONCLUSION: Using this systematic and targeted approach, there was a clear
      demand for this service from people of various ethnic backgrounds, of whom, one
      in two needed review from primary or secondary healthcare. Further work is
      required to assess the accuracy and clinical benefits of this community health
      screening approach.

PMID- 18036224
TI  - Hepatitis B virus genotypes circulating in Brazil: molecular characterization of
      genotype F isolates.
AB  - BACKGROUND: Hepatitis B virus (HBV) isolates have been classified in eight
      genotypes, A to H, which exhibit distinct geographical distributions. Genotypes
      A, D and F are predominant in Brazil, a country formed by a miscegenated
      population, where the proportion of individuals from Caucasian, Amerindian and
      African origins varies by region. Genotype F, which is the most divergent, is
      considered indigenous to the Americas. A systematic molecular characterization of
      HBV isolates from different parts of the world would be invaluable in
      establishing HBV evolutionary origins and dispersion patterns. A large-scale
      study is needed to map the region-by-region distribution of the HBV genotypes in
      Brazil. RESULTS: Genotyping by PCR-RFLP of 303 HBV isolates from HBsAg-positive
      blood donors showed that at least two of the three genotypes, A, D, and F, co
      circulate in each of the five geographic regions of Brazil. No other genotypes
      were identified. Overall, genotype A was most prevalent (48.5%), and most of
      these isolates were classified as subgenotype A1 (138/153; 90.2%). Genotype D was
      the most common genotype in the South (84.2%) and Central (47.6%) regions. The
      prevalence of genotype F was low (13%) countrywide. Nucleotide sequencing of the
      S gene and a phylogenetic analysis of 32 HBV genotype F isolates showed that a
      great majority (28/32; 87.5%) belonged to subgenotype F2, cluster II. The deduced
      serotype of 31 of 32 F isolates was adw4. The remaining isolate showed a leucine
      to-isoleucine substitution at position 127. CONCLUSION: The presence of genotypes
      A, D and F, and the absence of other genotypes in a large cohort of HBV infected
      individuals may reflect the ethnic origins of the Brazilian population. The high
      prevalence of isolates from subgenotype A1 (of African origin) indicates that the
      African influx during the colonial slavery period had a major impact on the
      circulation of HBV genotype A currently found in Brazil. Although most genotype F
      isolates belonged to cluster II, the presence of some isolates belonging to
      clusters I (subgroup Ib) and IV suggests the existence of two or more founder
      viral populations of genotype F in Brazil.

PMID- 18036226
TI  - The Oslo Health Study: Is bone mineral density higher in affluent areas?
AB  - BACKGROUND: Based on previously reported differences in fracture incidence in the
      socioeconomic less affluent Oslo East compared to the more privileged West, our
      aim was to study bone mineral density (BMD) in the same socioeconomic areas in
      Oslo. We also wanted to study whether possible associations were explained by
      socio-demographic factors, level of education or lifestyle factors. METHODS:
      Distal forearm BMD was measured in random samples of the participants in The Oslo
      Health Study by single energy x-ray absorptiometry (SXA). 578 men and 702 women
      born in Norway in the age-groups 40/45, 60 and 75 years were included in the
      analyses. Socioeconomic regions, based on a social index dividing Oslo in two
      regions - East and West, were used. RESULTS: Age-adjusted mean BMD in women
      living in the less affluent Eastern region was 0.405 g/cm2 and significantly
      lower than in West where BMD was 0.419 g/cm2. Similarly, the odds ratio of low
      BMD (Z-score </= -1) was 1.87 (95% CI: 1.22-2.87) in women in Oslo East compared
      to West. The same tendency, although not statistically significant, was also
      present in men. Multivariate analysis adjusted for education, marital status,
      body mass index, physical inactivity, use of alcohol and smoking, and in women
      also use of post-menopausal hormone therapy and early onset of menopause, did
      hardly change the association. Additional adjustments for employment status,
      disability pension and physical activity at work for those below the age of
      retirement, gave similar results. CONCLUSION: We found differences in BMD in
      women between different socioeconomic regions in Oslo that correspond to
      previously found differences in fracture rates. The association in men was not
      statistically significant. The differences were not explained by socio
      demographic factors, level of education or lifestyle factors.

PMID- 18036228
TI  - CD43 signals induce Type One lineage commitment of human CD4+ T cells.
AB  - BACKGROUND: The activation and effector phenotype of T cells depend on the
      strength of the interaction of the TcR with its cognate antigen and additional
      signals provided by cytokines and by co-receptors. Lymphocytes sense both the
      presence of an antigen and also clues from antigen-presenting cells, which
      dictate the requisite response. CD43 is one of the most abundant molecules on the
      surface of T cells; it mediates its own signalling events and cooperates with
      those mediated by the T cell receptor in T cell priming. We have examined the
      role of CD43 signals on the effector phenotype of adult CD4+ and CD8+ human T
      cells, both alone and in the presence of signals from the TcR. RESULTS: CD43
      signals direct the expression of IFNgamma in human T cells. In freshly isolated
      CD4+ T cells, CD43 signals potentiated expression of the IFNgamma gene induced by
      TcR activation; this was not seen in CD8+ T cells. In effector cells, CD43
      signals alone induced the expression of the IFNgamma gene in CD4+ T cells and to
      a lesser extent in CD8+ cells. The combined signals from CD43 and the TcR
      increased the transcription of the T-bet gene in CD4+ T cells and inhibited the
      transcription of the GATA-3 gene in both populations of T cells, thus
      predisposing CD4+ T cells to commitment to the T1 lineage. In support of this,
      CD43 signals induced a transient membrane expression of the high-affinity chains
      of the receptors for IL-12 and IFNgamma in CD4+ T cells. CD43 and TcR signals
      also cooperated with those of IL-12 in the induction of IFNgamma expression.
      Moreover, CD43 signals induced the co-clustering of IFNgammaR and the TcR and
      cooperated with TcR and IL-12 signals, triggering a co-capping of both receptors
      in CD4+ populations, a phenomenon that has been associated with a T1 commitment.
      CONCLUSION: Our results suggest a key role for CD43 signals in the
      differentiation of human CD4+ T cells into a T1 pattern.

PMID- 18036229
TI  - Immunological intervention in human diseases.
AB  - A recent Keystone Symposium Meeting on "Immunological Intervention in Human
      Disease" was held in Big Sky, Montana on January, 6-11, 2007, organized by
      Jacques Banchereau, Federica Sallusto and Robert Coffman. It brought together
      basic scientists and clinicians from both academia and the pharmaceutical
      industry to discuss how the immune system is involved in the development of human
      diseases, including cancer, allergy, autoimmunity, and infectious diseases. We
      highlight advances in our understanding of the pathogenesis of immune-mediated
      diseases and future approaches in the immune therapeutic interventions.
      Considerable progress in the development of model systems and methodologies to
      monitor human immune responses will help to develop and to evaluate new immune
      based therapies at pre-clinical and clinical studies.

PMID- 18036227
TI  - Analysis of gene expression during neurite outgrowth and regeneration.
AB  - BACKGROUND: The ability of a neuron to regenerate functional connections after
      injury is influenced by both its intrinsic state and also by extrinsic cues in
      its surroundings. Investigations of the transcriptional changes undergone by
      neurons during in vivo models of injury and regeneration have revealed many
      transcripts associated with these processes. Because of the complex milieu of
      interactions in vivo, these results include not only expression changes directly
      related to regenerative outgrowth and but also unrelated responses to surrounding
      cells and signals. In vitro models of neurite outgrowth provide a means to study
      the intrinsic transcriptional patterns of neurite outgrowth in the absence of
      extensive extrinsic cues from nearby cells and tissues. RESULTS: We have
      undertaken a genome-wide study of transcriptional activity in embryonic superior
      cervical ganglia (SCG) and dorsal root ganglia (DRG) during a time course of
      neurite outgrowth in vitro. Gene expression observed in these models likely
      includes both developmental gene expression patterns and regenerative responses
      to axotomy, which occurs as the result of tissue dissection. Comparison across
      both models revealed many genes with similar gene expression patterns during
      neurite outgrowth. These patterns were minimally affected by exposure to the
      potent inhibitory cue Semaphorin3A, indicating that this extrinsic cue does not
      exert major effects at the level of nuclear transcription. We also compared our
      data to several published studies of DRG and SCG gene expression in animal models
      of regeneration, and found the expression of a large number of genes in common
      between neurite outgrowth in vitro and regeneration in vivo. CONCLUSION: Many
      gene expression changes undergone by SCG and DRG during in vitro outgrowth are
      shared between these two tissue types and in common with in vivo regeneration
      models. This suggests that the genes identified in this in vitro study may
      represent new candidates worthy of further study for potential roles in the
      therapeutic regrowth of neuronal connections.

PMID- 18036230
TI  - Modulation of LPS stimulated NF-kappaB mediated Nitric Oxide production by
      PKCepsilon and JAK2 in RAW macrophages.
AB  - BACKGROUND: Nuclear factor kappa B (NF-kappaB) has been shown to play an
      important role in regulating the expression of many genes involved in cell
      survival, immunity and in the inflammatory processes. NF-kappaB activation
      upregulates inducible nitric oxide synthase leading to enhanced nitric oxide
      production during an inflammatory response. NF-kappaB activation is regulated by
      distinct kinase pathways independent of inhibitor of kappaB kinase (IKK). Here,
      we examine the role of protein kinase C isoforms and janus activated kinase 2
      (JAK2) activation in NF-kappaB activation and LPS-stimulated NO production.
      METHODS: Murine RAW 264.7 macrophages were treated with lipopolysaccharide (LPS),
      Phorbol 12-myristate 13-acetate (PMA) and a combination of LPS and PMA in the
      presence or absence of various inhibitors of PKC isoforms and JAK2. Nuclear
      translocation of the NF-kappaB p65 subunit, was assessed by Western blot analysis
      whilst NO levels were assessed by Greiss assay. RESULTS: LPS-stimulated NO
      production was attenuated by PMA whilst PMA alone did not affect NO release.
      These effects were associated with changes in p65 nuclear translocation. The
      PKCalpha, beta, gamma, delta and zeta inhibitor Go 6983 (Go) had no effect on LPS
      induced NO release. In contrast, Bisindolymalemide I (Bis), a PKC alpha, betaI,
      betaII, gamma, delta and epsilon isoform inhibitors completely inhibited LPS
      stimulated NO production without affecting p65 nuclear translocation.
      Furthermore, a partial inhibitory effect on LPS-induced NO release was seen with
      the JAK2 inhibitor AG-490 and the p38 MAPK inhibitor SB 203850. CONCLUSION: The
      results further define the role of NF-kappaB in LPS stimulated NO production in
      RAW macrophages. The data support a function for PKCepsilon, JAK2 and p38 MAPK in
      NF-kappaB activation following p65 nuclear import.

PMID- 18036231
TI  - Traumatic quadriceps rupture in a patient with patellectomy: a case report.
AB  - INTRODUCTION: Acute traumatic, unilateral, quadriceps rupture after patellectomy
      is rare. CASE PRESENTATION: We present a 42-year old male who experienced a
      unilateral left quadriceps tendon rupture following assault by four people.
      Twenty-seven years before this injury, the patient had suffered ipsilateral femur
      and comminuted patellar fractures, which were managed by intramedullary nailing
      and patellectomy respectively. We performed primary end to end repair of the torn
      tendon. Postoperatively, histology revealed findings consistent with pre-existent
      degenerative changes. The patient made good recovery, and returned to his former
      occupation which was reliant on his ability to drive. CONCLUSION: Degenerative
      changes of the tendon of the extensor mechanism of knee following patellectomy
      may predispose the quadriceps tendon to traumatic rupture. Early operative
      intervention and protracted rehabilitation are required to obtain the best
      functional results.

PMID- 18036232
TI  - LGMD2I in a North American population.
AB  - BACKGROUND: There is a marked variation in clinical phenotypes that have been
      associated with mutations in FKRP, ranging from severe congenital muscular
      dystrophies to limb-girdle muscular dystrophy type 2I (LGMD2I). METHODS: We
      screened the FKRP gene in two cohorts totaling 87 patients with the LGMD
      phenotype. RESULTS: The c.826C>A, p.L276I mutation was present in six patients
      and a compound heterozygote mutation in a seventh patient. Six patients had a
      mild LGMD2I phenotype, which resembles that of Becker muscular dystrophy. The
      other patient had onset before the age of 3 years, and thus may follow a more
      severe course. CONCLUSION: These findings suggest that LGMD2I may be common in
      certain North American populations. This diagnosis should be considered early in
      the evaluation of LGMD.

PMID- 18036233
TI  - Recombinant activated factor VII in cardiac surgery - first, do no harm.

PMID- 18036234
TI  - Down syndrome with microgranular variant of acute promyelocytic leukemia in a
      child: a case report.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) accounts for less than 10% of
      pediatric AML. Cases of APL in Down syndrome (DS) have been described in the
      literature rarely and it is rarer still to find the microgranular variant (M3v)
      of APL in trisomy 21 patients. CASE PRESENTATION: We present a case of a five
      year-old female with Down syndrome diagnosed with acute promyelocytic leukemia
      (APL). She came to our hospital with bleeding manifestations. Blood and bone
      marrow examination revealed promyelocytes showing a few fine granules and
      occasional Auer rods. Based on this morphology and cytochemistry, a diagnosis of
      APL microgranular variant (M3v) was made. CONCLUSION: This case report emphasizes
      the importance of a high index of suspicion in the diagnosis of acute
      promyelocytic leukemia microgranular variant in Down syndrome.

PMID- 18036235
TI  - The dimerization domain of HIV-1 viral infectivity factor Vif is required to
      block virion incorporation of APOBEC3G.
AB  - BACKGROUND: The HIV-1 accessory protein known as viral infectivity factor or Vif
      binds to the host defence factor human APOBEC3G (hA3G) and prevents its assembly
      with viral particles and mediates its elimination through ubiquitination and
      degradation by the proteosomal pathway. In the absence of Vif, hA3G becomes
      incorporated within viral particles. During the post entry phase of infection,
      hA3G attenuates viral replication by binding to the viral RNA genome and
      deaminating deoxycytidines to form deoxyuridines within single stranded DNA
      regions of the replicated viral genome. Vif dimerization has been reported to be
      essential for viral infectivity but the mechanistic requirement for Vif
      multimerization is unknown. RESULTS: We demonstrate that a peptide antagonist of
      Vif dimerization fused to the cell transduction domain of HIV TAT suppresses live
      HIV-1 infectivity. We show rapid cellular uptake of the peptide and cytoplasmic
      distribution. Robust suppression of viral infectivity was dependent on the
      expression of Vif and hA3G. Disruption of Vif multimerization resulted in the
      production of virions with markedly increased hA3G content and reduced
      infectivity. CONCLUSION: The role of Vif multimerization in viral infectivity of
      nonpermissive cells has been validated with an antagonist of Vif dimerization. An
      important part of the mechanism for this antiretroviral effect is that blocking
      Vif dimerization enables hA3G incorporation within virions. We propose that Vif
      multimers are required to interact with hA3G to exclude it from viral particles
      during their assembly. Blocking Vif dimerization is an effective means of
      sustaining hA3G antiretroviral activity in HIV-1 infected cells. Vif dimerization
      is therefore a validated target for therapeutic HIV-1/AIDS drug development.

PMID- 18036237
TI  - A case report of bilateral synovial chondromatosis of the ankle.
AB  - BACKGROUND: Synovial chondromatosis is a rare, generally benign condition which
      affects synovial membranes. It most commonly involves large joints such as the
      knee, hip, and elbow, but its presence in smaller joints has also been reported.
      The diagnosis of synovial chondromatosis is commonly made following a thorough
      history, physical examination, and radiographic examination. Patients may report
      pain and swelling within a joint which is often aggravated with physical
      activity. CASE PRESENTATION: A rare case of bilateral synovial chondromatosis of
      the ankle is reviewed. A 26 year-old male presented with chronic bilateral ankle
      pain. Physical examination suggested and imaging confirmed multiple synovial
      chondromatoses bilaterally, likely secondary to previous trauma. CONCLUSION: The
      clinical and imaging findings, along with potential differential diagnoses, are
      described. Since this condition tends to be progressive but self-limiting,
      indications for surgery depend on the level of symptomatic presentation in
      addition to the functional demands of the patient. Following a surgical
      consultation, it was decided that it was not appropriate to pursue surgery at the
      present time.

PMID- 18036236
TI  - Correlates of patient satisfaction with physician visit: differences between
      elderly and non-elderly survey respondents.
AB  - BACKGROUND: Few studies document differences in patient satisfaction with
      physicians in the elderly (> or = 65 years) and compare it to non-elderly (<65
      years) patients. METHODS: A cross-sectional survey study on a convenience sample
      of 20,901 patients rated their recent visit to a physician through a web-based
      survey. Survey included validated questions based on aspects of physician care
      practice such as "friendliness", wait times and time spent with doctor. These
      scales were then used to measure patient satisfaction with physician. Statistical
      analysis involved pair-matching of non-elderly patients with elderly patients
      (both cohorts, n = 507 each) using propensity scores. RESULTS: Even though
      elderly and non-elderly patients had similar waiting times, elderly patients gave
      higher physician satisfaction scores than non-elderly patients (all p < 0.05).
      When predictors of physician satisfaction ratings were examined, shorter waiting
      time was more significantly associated with better treatment satisfaction in non
      elderly patients (partial rho = -0.25 in the non-elderly compared to partial rho
      = -0.11 in elderly, p < 0.05). Increased time spent with the physician was more
      significantly correlated with higher physician satisfaction ratings in the non
      elderly patients (partial rho = 0.38 in the non-elderly compared to partial rho =
      0.18, p < 0.001). CONCLUSION: Increased patient satisfaction ratings of the non
      elderly were associated more strongly with shorter waiting times than in the
      elderly. However overall, elderly patients reported similar waiting times and
      better physician satisfaction scores. Similarly, higher physician satisfaction in
      non-elderly patients were more strongly associated with increased time spent with
      physician than in the elderly patients.

PMID- 18036238
TI  - Gait analysis in a murine model of collagen-induced arthritis.
AB  - Murine collagen-induced arthritis (CIA) has become a valuable animal model for
      elucidating pathogenic mechanisms and evaluating therapeutic effects for
      rheumatoid arthritis. Recent advances in digital imaging and computer technology
      have enabled gait analysis to develop into a powerful tool for objectively
      detecting functional deficits in human and animal models. The present study
      explored the use of non-invasive video-capture gait analysis in the evaluation of
      a murine CIA model. CIA was induced in 45 female DBA/1LacJ mice (8 to 10 weeks
      old) by immunization with lyophilized bovine articular type II collagen. Gait
      parameters were determined by ventral plane videography and were correlated to
      traditional arthritis clinical scores. Our results showed that increases in
      clinical scores that measure the severity of CIA corresponded to changes in
      multiple gait parameters that reflect both morphologic (increases in paw area)
      and functional (increase in stride frequency, decrease in stride length, hind
      limb paw placement angle, as well as stride, stance, and braking times) deficits.
      Our work indicated that the non-invasive video-capture device may be used as a
      simple and objective data acquisition system for quantifying gait disturbances in
      CIA mice for the investigation of mechanisms and the evaluation of therapeutic
      agents.

PMID- 18036239
TI  - Development of an in vitro three dimensional loading-measurement system for long
      bone fixation under multiple loading conditions: a technical description.
AB  - The purpose of this investigation was to design and verify the capabilities of an
      in vitro loading-measurement system that mimics in vivo unconstrained three
      dimensional (3D) relative motion between long bone ends, applies uniform load
      components over the entire length of a test specimen, and measures 3D relative
      motion between test segment ends to directly determine test segment construct
      stiffness free of errors due to potting-fixture-test machine finite
      stiffness.Intact equine cadaveric radius bones, which were subsequently
      osteotomized/ostectomized and instrumented with bone plates were subjected to non
      destructive axial, torsion, and 4-point bending loads through fixtures designed
      to allow unconstrained components of non-load associated 3D relative motion
      between radius ends. 3D relative motion between ends of a 50 mm long test segment
      was measured by an infrared optical tracking system to directly determine its
      stiffness. Each specimen was then loaded to ultimate failure in either torsion or
      bending. Cortical bone cross-section diameters and published bone biomechanical
      properties were substituted into classical mechanics equations to predict the
      intact test segment theoretical stiffness for comparison and thus loading
      measurement system verification.Intact measured stiffness values were the same
      order of magnitude as theoretically predicted. The primary component of relative
      motion between ends of the test segment corresponded to that of the applied load
      with the other 3D components being evident and consistent in relative magnitude
      and direction for unconstrained loading of an unsymmetrical double plate oblique
      fracture configuration. Bone failure configurations were reproducible and
      consistent with theoretically predicted.The 3D loading-measurement system
      designed: a) mimics unconstrained relative 3D motion between radius ends that
      occurs in clinical situations, b) applies uniform compression, torsion, and 4
      point bending loads over the entire length of the test specimen, c) measures
      interfragmentary 3D relative motion between test segment ends to directly
      determine stiffness thus being void of potting-fixture-test machine stiffness
      error, and d) has the resolution to detect differences in the 3D motion and
      stiffness of intact as well osteotomized-instrumented and ostectomized
      instrumented equine radii.

PMID- 18036240
TI  - microRNAs in viral oncogenesis.
AB  - MicroRNAs are a recently discovered class of small noncoding functional RNAs.
      These molecules mediate post-transcriptional regulation of gene expression in a
      sequence specific manner. MicroRNAs are now known to be key players in a variety
      of biological processes and have been shown to be deregulated in a number of
      cancers. The discovery of viral encoded microRNAs, especially from a family of
      oncogenic viruses, has attracted immense attention towards the possibility of
      microRNAs as critical modulators of viral oncogenesis. The host-virus crosstalk
      mediated by microRNAs, messenger RNAs and proteins, is complex and involves the
      different cellular regulatory layers. In this commentary, we describe models of
      microRNA mediated viral oncogenesis.

PMID- 18036241
TI  - An interdisciplinary guideline development process: the Clinic on Low-back pain
      in Interdisciplinary Practice (CLIP) low-back pain guidelines.
AB  - BACKGROUND: Evaluation of low-back pain guidelines using Appraisal of Guidelines
      Research and Evaluation (AGREE) criteria has shown weaknesses, particularly in
      stakeholder involvement and applicability of recommendations. The objectives of
      this project were to: 1) develop a primary care interdisciplinary clinical
      practice guideline aimed at preventing prolonged disability from low-back pain,
      using a community of practice approach, and 2) assess the participants'
      impressions with the process, and evaluate the relationship between participant
      characteristics and their participation. METHODS: Ten stakeholder representatives
      recruited 136 clinicians to participate in this community of practice. Clinicians
      were drawn from the following professions: physiotherapists (46%), occupational
      therapists (37%), and family physicians (17%). Using previously published
      guidelines, systematic reviews, and meta-analyses, a first draft of the
      guidelines was presented to the community of practice. Four communication tools
      were provided for discussion and exchanges with experts: a web-based discussion
      forum, an anonymous comment form, meetings, and a symposium. Participants were
      prompted for comments on interpretation, clarity, and applicability of the
      recommendations. Clinical management recommendations were revised following these
      exchanges. At the end of the project, a questionnaire was sent to the
      participants to assess satisfaction towards the guidelines and the development
      process. RESULTS: Twelve clinical management recommendations on management of low
      back pain and persistent disability were initially developed. These were
      discussed through 188 comments posted on the discussion forum and 103 commentary
      forms submitted. All recommendations were modified following input of the
      participants. A clinical algorithm summarizing the guidelines was also developed.
      A response rate of 75% was obtained for the satisfaction questionnaire. The
      majority of respondents appreciated the development process and agreed with the
      guideline content. Most participants thought recommendations improved between
      versions, and that participant comments contributed to this improvement. All
      stakeholders officially endorsed the guidelines. CONCLUSION: The community of
      practice approach was a successful method to develop guidelines on low-back pain,
      with participants providing information to improve guideline recommendations. The
      information technology infrastructure that was developed remains for continuous
      interdisciplinary exchanges and updating of the guidelines.

PMID- 18036242
TI  - The new biology: beyond the Modern Synthesis.
AB  - BACKGROUND: The last third of the 20th Century featured an accumulation of
      research findings that severely challenged the assumptions of the "Modern
      Synthesis" which provided the foundations for most biological research during
      that century. The foundations of that "Modernist" biology had thus largely
      crumbled by the start of the 21st Century. This in turn raises the question of
      foundations for biology in the 21st Century. CONCLUSION: Like the physical
      sciences in the first half of the 20th Century, biology at the start of the 21st
      Century is achieving a substantive maturity of theory, experimental tools, and
      fundamental findings thanks to relatively secure foundations in genomics.
      Genomics has also forced biologists to connect evolutionary and molecular
      biology, because these formerly Balkanized disciplines have been brought together
      as actors on the genomic stage. Biologists are now addressing the evolution of
      genetic systems using more than the concepts of population biology alone, and the
      problems of cell biology using more than the tools of biochemistry and molecular
      biology alone. It is becoming increasingly clear that solutions to such basic
      problems as aging, sex, development, and genome size potentially involve elements
      of biological science at every level of organization, from molecule to
      population. The new biology knits together genomics, bioinformatics, evolutionary
      genetics, and other such general-purpose tools to supply novel explanations for
      the paradoxes that undermined Modernist biology.

PMID- 18036243
TI  - Effect of immunization against ox-LDL with two different antigens on formation
      and development of atherosclerosis.
AB  - Several studies were pointed to oxidized LDL (ox-LDL) as one of the main
      immunogenes which have important roles in primary lesions of atherosclerosis. In
      this study, by immunization against ox-LDL with two different antigens in an
      animal model (rabbit) and consideration of its effect on two different dietary
      regimens; we tried to clear relation between immune system and atherosclerosis.
      METHODS: LDL was isolated from hypercholesterolemic rabbits plasma and oxidized
      with MDA or Cu++. Rabbits were divided to three groups and immunized with MDA-LDL
      or Cu-LDL or phosphate-buffer (PBS) as a control group. Immunization was repeated
      after 2, 4, 6, and 8 weeks and concentration of antibodies against ox-LDL was
      measured in each stage. After immunization, rabbits in each group were divided to
      two subgroups based on the dietary regimen (fed normal or high cholesterol diet).
      At the beginning and the end of the study, biochemical factors were measured.
      Also, fatty streaks in aorta and left and right coronary arteries evaluated.
      RESULTS: Immunization with Cu2+-LDL and MDA-LDL induced statistically significant
      antibodies against ox-LDL. In hypercholesterolemic rabbits immunized with MDA-LDL
      the level of cholesterol, LDL-cholesterol, triglyceride, fasting blood sugar and
      fatty streak lesions in aorta and right coronary arteries were significantly
      decreased as compared with non-immunized high-cholesterol group. Immunization
      with Cu2+-LDL in hypercholesterolemic rabbits significantly decreased
      triglyceride, fasting blood sugar, cholesterol and CRP. No significant
      differences were detected in the fatty streak lesions in this group as compared
      with non-immunized high-cholesterol diet. In groups under normal diet immunized
      with MDA-LDL or Cu2+-LDL no significant effect on biochemical factors and
      atherosclerotic lesions were observed. CONCLUSION: This study indicates that
      although the effect of produced antibodies in several methods and different
      dietary regimens is different, immunization against ox-LDL is antiatherogenic.

PMID- 18036244
TI  - Role of HIV-1 subtype C envelope V3 to V5 regions in viral entry, coreceptor
      utilization and replication efficiency in primary T-lymphocytes and monocyte
      derived macrophages.
AB  - BACKGROUND: Several subtypes of HIV-1 circulate in infected people worldwide,
      including subtype B in the United States and subtype C in Africa and India. To
      understand the biological properties of HIV-1 subtype C, including cellular
      tropism, virus entry, replication efficiency and cytopathic effects, we
      reciprocally inserted our previously characterized envelope V3-V5 regions derived
      from 9 subtype C infected patients from India into a subtype B molecular clone,
      pNL4-3. Equal amounts of the chimeric viruses were used to infect T-lymphocyte
      cell lines (A3.01 and MT-2), coreceptor cell lines (U373-MAGI-CCR5/CXCR4),
      primary blood T-lymphocytes (PBL) and monocyte-derived macrophages (MDM).
      RESULTS: We found that subtype C envelope V3-V5 region chimeras failed to
      replicate in T-lymphocyte cell lines but replicated in PBL and MDM. In addition,
      these chimeras were able to infect U373MAGI-CD4+-CCR5+ but not U373MAGI-CD4+
      CXCR4+ cell line, suggesting CCR5 coreceptor utilization and R5 phenotypes. These
      subtype C chimeras were unable to induce syncytia in MT-2 cells, indicative of
      non-syncytium inducing (NSI) phenotypes. More importantly, the subtype C envelope
      chimeras replicated at higher levels in PBL and MDM compared with subtype B
      chimeras and isolates. Furthermore, the higher levels subtype C chimeras
      replication in PBL and MDM correlated with increased virus entry in U373MAGI-CD4+
      CCR5+. CONCLUSION: Taken together, these results suggest that the envelope V3 to
      V5 regions of subtype C contributed to higher levels of HIV-1 replication
      compared with subtype B chimeras, which may contribute to higher viral loads and
      faster disease progression in subtype C infected individuals than other subtypes
      as well as rapid HIV-1 subtype C spread in India.

PMID- 18036245
TI  - Chondromyxoid fibroma of rib with a novel chromosomal translocation: a report of
      four additional cases at unusual sites.
AB  - BACKGROUND: Chondromyxoid fibromas (CMFs) are rare benign chondroid/myxoid matrix
      producing tumors that occur in metaphyses of long tubular bones, and very rarely
      in small bones of hands and feet. Flat bone involvement is even more uncommon.
      Prior cytogenetic analyses have identified complex abnormalities involving
      chromosome 6 in the majority of cases. METHODS: A search for CMF over an 8-year
      period (1999-2006) from the surgical pathology files of our institution yielded
      16 cases. Four cases occurred in relatively unusual regions, three from the small
      bones of distal extremities and one from the rib. The rib lesion was submitted
      for routine cytogenetic analysis. RESULTS: Radiographic studies revealed that all
      four lesions were well-defined expansile radiolucent lesions which expanded the
      bony cortices with lobulated margins, sclerotic rim, septation, and no
      calcification. Morphologically, all four lesions showed typical features of CMF
      and had low proliferative index with Ki-67. Cytogenetic analysis on the rib
      lesion revealed a novel chromosomal translocation, t(1;5)(p13;p13). None of the
      four patients had a recurrence after a mean duration of follow-up of 24 months.
      CONCLUSION: CMF originating in unusual locations should be distinguished from
      chondrosarcomas, especially on small biopsies, and should be included in the
      differential diagnosis. As previously noted in the literature, the cells can be
      positive for actin but unlike conventional chondroid neoplasms can be negative
      for S-100. To our knowledge, this is the first report describing a novel
      chromosomal translocation, t(1;5)(p13;p13) in CMF.

PMID- 18036246
TI  - Epidermal growth factor potentiates in vitro metastatic behaviour of human
      prostate cancer PC-3M cells: involvement of voltage-gated sodium channel.
AB  - BACKGROUND: Although a high level of functional voltage-gated sodium channel
      (VGSC) expression has been found in strongly metastatic human and rat prostate
      cancer (PCa) cells, the mechanism(s) responsible for the upregulation is unknown.
      The concentration of epidermal growth factor (EGF), a modulator of ion channels,
      in the body is highest in prostatic fluid. Thus, EGF could be involved in the
      VGSC upregulation in PCa. The effects of EGF on VGSC expression in the highly
      metastatic human PCa PC-3M cell line, which was shown previously to express both
      functional VGSCs and EGF receptors, were investigated. A quantitative approach,
      from gene level to cell behaviour, was used. mRNA levels were determined by real
      time PCR. Protein expression was studied by Western blots and immunocytochemistry
      and digital image analysis. Functional assays involved measurements of transverse
      migration, endocytic membrane activity and Matrigel invasion. RESULTS: Exogenous
      EGF enhanced the cells' in vitro metastatic behaviours (migration, endocytosis
      and invasion). Endogenous EGF had a similar involvement. EGF increased VGSC
      Nav1.7 (predominant isoform in PCa) mRNA and protein expressions. Co-application
      of the highly specific VGSC blocker tetrodotoxin (TTX) suppressed the effect of
      EGF on all three metastatic cell behaviours studied. CONCLUSION: 1) EGF has a
      major involvement in the upregulation of functional VGSC expression in human PCa
      PC-3M cells. (2) VGSC activity has a significant intermediary role in
      potentiating effect of EGF in human PCa.

PMID- 18036247
TI  - Validity and reliability testing of two instruments to measure breast cancer
      patients' concerns and information needs relating to radiation therapy.
AB  - BACKGROUND: It is difficult to determine the most effective approach to patient
      education or tailor education interventions for patients in radiotherapy without
      tools that assess patients' specific radiation therapy information needs and
      concerns. Therefore, the aim of this study was to develop psychometrically sound
      tools to adequately determine the concerns and information needs of cancer
      patients during radiation therapy. PATIENTS AND METHODS: Two tools were developed
      to (1) determine patients concerns about radiation therapy (RT Concerns Scale)
      and (2) ascertain patient's information needs at different time point during
      their radiation therapy (RT Information Needs Scale). Tools were based on
      previous research by the authors, published literature on breast cancer and
      radiation therapy and information behaviour research. Thirty-one breast cancer
      patients completed the questionnaire on one occasion and thirty participants
      completed the questionnaire on a second occasion to facilitate test-retest
      reliability. One participant's responses were removed from the analysis. Results
      were analysed for content validity, internal consistency and stability over time.
      RESULTS: Both tools demonstrated high internal consistency and adequate stability
      over time. The nine items in the RT Concerns Scale were retained because they met
      all pre-set psychometric criteria. Two items were deleted from the RT Information
      Needs Scale because they did not meet content validity criteria and did not
      achieve pre-specified criteria for internal consistency. This tool now contains
      22 items. CONCLUSION: This paper provides preliminary data suggesting that the
      two tools presented are reliable and valid and would be suitable for use in
      trials or in the clinical setting.

PMID- 18036248
TI  - Aberrant overexpression of an epithelial marker, 14-3-3sigma, in a subset of
      hematological malignancies.
AB  - BACKGROUND: 14-3-3sigma is a p53-mediated cell-cycle inhibitor in epithelial
      cells. The expression of 14-3-3sigma is frequently altered in cancers of
      epithelial origin associated with altered DNA methylation. Since its involvement
      in a non-epithelial tumor is unknown, we examined 14-3-3sigma expression in
      patients with haematological malignancies. METHODS: We analyzed 41 hematopoietic
      cell lines and 129 patients with a variety of hematological malignancies for 14-3
      3sigma expression with real-time RT-PCR. We also examined protein levels by
      Western blot analysis and DNA methylation status of the 14-3-3sigma gene by
      methylation-specific PCR analysis of bisulfite-treated DNA. In addition,
      mutations of p53 gene were identified by RT-PCR-SSCP analysis and the expression
      levels of 14-3-3sigma were compared with those of other cell-cycle inhibitor
      genes, CDKN2A and ARF. RESULTS: The expression levels of 14-3-3sigma mRNA in
      almost all cell lines were low and comparable to those in normal hematopoietic
      cells except for 2 B-cell lines. On the contrary, 14-3-3sigma mRNA was aberrantly
      overexpressed frequently in mature lymphoid malignancies (30 of 93, 32.3%) and
      rarely in acute leukemia (3 of 35, 8.6%). 14-3-3sigma protein was readily
      detectable and roughly reflected the mRNA level. In contrast to epithelial
      tumors, methylation status of the 14-3-3sigma gene was not associated with
      expression in hematological malignancies. Mutations of p53 were identified in 12
      patients and associated with lower expression of 14-3-3sigma. The expression
      levels of 14-3-3sigma, CDKN2A and ARF were not correlated with but rather
      reciprocal to one another, suggesting that simultaneous overexpression of any two
      of them is incompatible with tumor growth. CONCLUSION: 14-3-3sigma, an epithelial
      cell marker, was overexpressed significantly in a subset of mature lymphoid
      malignancies. This is the first report of aberrant 14-3-3sigma expression in non
      epithelial tumors in vivo. Since the significance of 14-3-3sigma overexpression
      is unknown even in epithelial tumors such as pancreatic cancers, further analysis
      of regulation and function of the 14-3-3sigma gene in non-epithelial as well as
      epithelial tumors is warranted.

PMID- 18036249
TI  - Tissue is the issue-sarcoidosis following ABVD chemotherapy for Hodgkin's
      lymphoma: a case report.
AB  - Thirty two year old Caucasian female presented 2 months post partum with fevers,
      cough and shortness of breath. CT scan of the chest to rule out pulmonary
      embolism revealed mediastinal lymphadenopathy. Biopsy of the nodes revealed
      classic Hodgkin's lymphoma and she received ABVD chemotherapy. She was in
      remission as confirmed by a PET/CT scan. Five months later she had another PET/CT
      scan which showed areas of hypermetabolism indicating a possible relapse. Biopsy
      revealed sarcoidosis. She received steroids and 18 months later remained in
      clinical remission. This rare case of sarcoid following classic Hodgkin's
      lymphoma illustrates that clinical presentation, physical exam, lab
      investigations and even PET/CT scans may not be able to discriminate between
      Hodgkin's lymphoma and sarcoidosis. Tissue biopsy and pathological diagnosis
      remain the gold standard.

PMID- 18036250
TI  - Function and anatomy of plant siRNA pools derived from hairpin transgenes.
AB  - BACKGROUND: RNA interference results in specific gene silencing by small
      interfering RNAs (siRNAs). Synthetic siRNAs provide a powerful tool for
      manipulating gene expression but high cost suggests that novel siRNA production
      methods are desirable. Strong evolutionary conservation of siRNA structure
      suggested that siRNAs will retain cross-species function and that transgenic
      plants expressing heterologous siRNAs might serve as useful siRNA bioreactors.
      Here we report a detailed evaluation of the above proposition and present
      evidence regarding structural features of siRNAs extracted from plants. RESULTS:
      Testing the gene silencing capacity of plant-derived siRNAs in mammalian cells
      proved to be very challenging and required partial siRNA purification and design
      of a highly sensitive assay. Using the above assay we found that plant-derived
      siRNAs are ineffective for gene silencing in mammalian cells. Plant-derived
      siRNAs are almost exclusively double-stranded and most likely comprise a mixture
      of bona fide siRNAs and aberrant partially complementary duplexes. We also
      provide indirect evidence that plant-derived siRNAs may contain a hitherto
      undetected physiological modification, distinct from 3' terminal 2-O-methylation.
      CONCLUSION: siRNAs produced from plant hairpin transgenes and extracted from
      plants are ineffective for gene silencing in mammalian cells. Thus our findings
      establish that a previous claim that transgenic plants offer a cost-effective,
      scalable and sustainable source of siRNAs is unwarranted. Our results also
      indicate that the presence of aberrant siRNA duplexes and possibly a plant
      specific siRNA modification, compromises the gene silencing capacity of plant
      derived siRNAs in mammalian cells.

PMID- 18036251
TI  - Chylous ascites associated with chylothorax; a rare sequela of penetrating
      abdominal trauma: a case report.
AB  - We present the case of a patient with the rare combination of chylous ascites
      and chylothorax resulting from penetrating abdominal injury. This patient was
      successfully managed with total parenteral nutrition. This case report is used to
      highlight the clinical features and management options of this uncommon but
      challenging clinical problem.

PMID- 18036252
TI  - Validity of electron beam computed tomography for coronary artery disease:
      asystematic review and meta-analysis.
AB  - BACKGROUND: Electron beam computed tomography (EBCT) is a method for measuring
      coronary calcification and has been promoted as a possible non-invasive
      screening/diagnostic tool for coronary artery disease (CAD). Our objective was to
      carry out a systematic review and meta-analysis of EBCT for the screening of
      asymptomatic patients and the diagnosis of symptomatic patients for CAD. METHODS:
      Studies were identified from the PUBMED, MEDLINE, EMBASE, Current Contents,
      INAHTA and Cochrane Collaboration databases. We identified studies published in
      English evaluating EBCT using: (1) a prospective design among asymptomatic
      patients where CAD was measured in terms of clinical outcomes (e.g. myocardial
      infarction, death, revascularization); and (2)a cross-sectional design among
      symptomatic patients where CAD was measured by coronary angiography. We compared
      the risk of CAD in EBCT score categories defined as low (0-10), moderate (11-400)
      and high (>400). A hierarchical meta-analysis was used to pool risk ratios
      comparing categories across studies. RESULTS: We identified 9 studies of
      asymptomatic patients and 10 studies of symptomatic patients. In both types of
      studies, we found variability in EBCT category distribution and risk of CAD
      within categories. For studies of asymptomatic patients we estimated the
      following risk ratios (95% credible intervals): moderate versus low 3.5 (2.4,
      5.1) and high versus low 9.9 (5.3, 17.6). Similar results were obtained for
      studies of symptomatic patients. Ratios comparing the risk of no CAD among
      symptomatic patients were as follows: moderate versus low 0.5 (0.3, 0.8) and high
      versus low 0.12 (0.05, 0.2). CONCLUSION: Increasing EBCT scores indicate higher
      risk for CAD in both asymptomatic and symptomatic patients. In general,
      asymptomatic patients with EBCT scores in the high category can perhaps be
      considered for preventive medical therapy and risk factor modification.
      Symptomatic patients with EBCT scores in the low category can perhaps, at least
      temporarily, avoid invasive coronary angiography. However, the non-uniform
      quality of studies and the lack of availability of individual-level data preclude
      the extension of our results to individual patients.

PMID- 18036253
TI  - An outbreak of cardiovascular syndromes requiring urgent medical treatment and
      its association with environmental factors: an ecological study.
AB  - BACKGROUND: In April 2005, syndromic surveillance based on statistical control
      chart methods in Sydney, Australia, signalled increasing incidence of urgent
      emergency department visits for cardiovascular and chest pain syndromes compared
      to the preceding twelve months. This paper aimed to determine whether
      environmental factors could have been responsible for this 'outbreak'. METHODS:
      The outcome studied was daily counts of emergency department visits for
      cardiovascular or chest pain syndromes that were considered immediately or
      imminently life threatening on arrival at hospital. The outbreak had a mean daily
      count of 5.7 visits sustained for eight weeks, compared with 4.0 in the same
      months in previous years. Poisson regression was used to systematically assess
      the emergency department visits in relation to available daily weather and
      pollution variables by first finding the best model that explained short-term
      variation in the outcome over the period 25 January 2002 to 31 May 2005, and then
      assessing interactions of all available variables with the 'outbreak' period,
      April-May 2005. Rate ratios were estimated for an interquartile increase in each
      variable meaning that the ratio measures the relative increase (or decrease) in
      the emergency department visits for an interquartile increase in the weather or
      pollution variable. The rate ratios for the outbreak period measure the relative
      increase (or decrease) in the emergency department visits for an interquartile
      increase in the weather or pollution variable during the outbreak period only.
      RESULTS: The best fitting model over the whole study period included minimum
      temperature with a rate ratio (RR) of 0.86 (95% confidence interval (CI), 0.77
      0.96), maximum relative humidity of 1.09 (95% CI 1.05-1.14) and minimum daily
      particulate matter less than 10 microns (PM10) of 1.05 (95% CI, 1.01-1.09).
      During the outbreak period, maximum temperature (RR 1.27, 95% CI 1.03-1.57),
      solar radiation (RR 1.44, 95% CI, 1.00-2.07) and ozone (RR 1.13, 95% CI 1.01
      1.26) were associated with the outcome. CONCLUSION: The increase may have been
      associated with photochemical pollution. Syndromic surveillance can identify
      outbreaks of non-communicable diseases associated with environmental factors.

PMID- 18036254
TI  - The ethics of donation and transplantation: are definitions of death being
      distorted for organ transplantation?
AB  - A recent commentary defends 1) the concept of 'brain arrest' to explain what
      brain death is, and 2) the concept that death occurs at 2-5 minutes after absent
      circulation. I suggest that both these claims are flawed. Brain arrest is said to
      threaten life, and lead to death by causing a secondary respiratory then cardiac
      arrest. It is further claimed that ventilation only interrupts this way that
      brain arrest leads to death. These statements imply that brain arrest is not
      death itself. Brain death is a devastating state that leads to death when
      intensive care, which replaces some of the brain's vital functions such as
      breathing, is withdrawn and circulation stops resulting in irreversible loss of
      integration of the organism. Circulatory death is said to occur at 2-5 minutes
      after absent circulation because, in the context of DCD, the intent is to not
      attempt reversal of the absent circulation. No defense of this weak construal of
      irreversible loss of circulation is given. This means that patients in identical
      physiologic states are dead (in the DCD context) or alive (in the resuscitation
      context); the current state of death (at 2-5 minutes) is contingent on a future
      event (whether there will be resuscitation) suggesting backward causation; and
      the commonly used meaning of irreversible as 'not capable of being reversed' is
      abandoned. The literature supporting the claim that autoresuscitation does not
      occur in the context of no cardiopulmonary resuscitation is shown to be very
      limited. Several cases of autoresuscitation are summarized, suggesting that the
      claim that these cases are not applicable to the current debate may be premature.
      I suggest that brain dead and DCD donors are not dead; whether organs can be
      harvested before death from these patients whose prognosis is death should be
      debated urgently.

PMID- 18036255
TI  - Differential expression of papillomavirus L1 proteins encoded by authentic and
      codon modified L1 genes in methylcellulose-treated mouse keratinocytes.
AB  - Papillomaviruses (PVs) are double-stranded DNA viruses that infect keratinocytes
      in differentiating epithelia and induce hyperproliferative lesions. Here, we used
      methylcellulose to induce cell differentiation of primary mouse keratinocytes
      (KCs) in in vitro culture and assessed the expression of authentic and codon
      modified version of L1 capsid genes from two PV types (HPV6b and BPV1). Based on
      the quantitative RT-PCR analysis, methylcellulose treatment did not influence the
      transcriptional expression of both authentic and codon-modified L1 genes in KCs.
      Western blot showed that methylcellulose significantly increased the levels of
      the L1 proteins expressed from two authentic L1 genes. Conversely,
      methylcellulose dramatically decreased L1 protein expression in KCs transfected
      with two codon-modified L1 expression constructs. These data suggest that L1
      protein expression is associated with KC differentiation induced by
      methylcellulose treatment and regulated at the post-transcriptional level.

PMID- 18036256
TI  - Antibody microarray analysis of cell surface antigens on CD4+ and CD8+ T cells
      from HIV+ individuals correlates with disease stages.
AB  - BACKGROUND: Expression levels of cell surface antigens such as CD38 and HLA-DR
      are related to HIV disease stages. To date, the immunophenotyping of cell surface
      antigens relies on flow cytometry, allowing estimation of 3-6 markers at a time.
      The recently described DotScan antibody microarray technology enables the
      simultaneous analysis of a large number of cell surface antigens. This new
      technology provides new opportunities to identify novel differential markers
      expressed or co-expressed on CD4+ and CD8+ T cells, which could aid in defining
      the stage of evolution of HIV infection and the immune status of the patient.
      RESULTS: Using this new technology, we compared cell surface antigen expression
      on purified CD4+ and CD8+ T cells between 3 HIV disease groups (long-term non
      progressors controlling viremia naturally; HIV+ patients on highly active
      antiretroviral therapy (HAART) with HIV plasma viral loads <50 copies/ml; and
      HIV+ patients with viremia during HAART) and uninfected controls. Pairwise
      comparisons identified 17 statistically differential cell surface antigens
      including 5 novel ones (CD212b1, CD218a, CD183, CD3 epsilon and CD9), not
      previously reported. Notably, changes in activation marker expression were more
      pronounced in CD8+ T cells, whereas changes in the expression of cell membrane
      receptors for cytokines and chemokines were more pronounced in CD4+ T cells.
      CONCLUSION: Our study not only confirmed cell surface antigens previously
      reported to be related to HIV disease stages, but also identified 5 novel ones.
      Of these five, three markers point to major changes in responsiveness to certain
      cytokines, which are involved in Th1 responses. For the first time our study
      shows how density of cell surface antigens could be efficiently exploited in an
      array manner in relation to HIV disease stages. This new platform of identifying
      disease markers can be further extended to study other diseases.

PMID- 18036257
TI  - Single nucleotide polymorphisms in bone turnover-related genes in Koreans: ethnic
      differences in linkage disequilibrium and haplotype.
AB  - BACKGROUND: Osteoporosis is defined as the loss of bone mineral density that
      leads to bone fragility with aging. Population-based case-control studies have
      identified polymorphisms in many candidate genes that have been associated with
      bone mass maintenance or osteoporotic fracture. To investigate single nucleotide
      polymorphisms (SNPs) that are associated with osteoporosis, we examined the
      genetic variation among Koreans by analyzing 81 genes according to their function
      in bone formation and resorption during bone remodeling. METHODS: We resequenced
      all the exons, splice junctions and promoter regions of candidate osteoporosis
      genes using 24 unrelated Korean individuals. Using the common SNPs from our study
      and the HapMap database, a statistical analysis of deviation in heterozygosity
      depicted. RESULTS: We identified 942 variants, including 888 SNPs, 43
      insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557
      (63%) had been previously identified and 331 (37%) were newly discovered in the
      Korean population. When compared SNPs in the Korean population with those in
      HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations
      and 20% of those in Caucasian and African subpopulations were significantly
      differentiated from the Hardy-Weinberg expectations. In addition, an analysis of
      the genetic diversity showed that there were no significant differences among
      Korean, Han Chinese and Japanese populations, but African and Caucasian
      populations were significantly differentiated in selected genes. Nevertheless, in
      the detailed analysis of genetic properties, the LD and Haplotype block patterns
      among the five sub-populations were substantially different from one another.
      CONCLUSION: Through the resequencing of 81 osteoporosis candidate genes, 118
      unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the
      Korean population. In addition, using the common SNPs between our study and
      HapMap, an analysis of genetic diversity and deviation in heterozygosity was
      performed and the polymorphisms of the above genes among the five populations
      were substantially differentiated from one another. Further studies of
      osteoporosis could utilize the polymorphisms identified in our data since they
      may have important implications for the selection of highly informative SNPs for
      future association studies.

PMID- 18036258
TI  - Evaluating the protein coding potential of exonized transposable element
      sequences.
AB  - BACKGROUND: Transposable element (TE) sequences, once thought to be merely
      selfish or parasitic members of the genomic community, have been shown to
      contribute a wide variety of functional sequences to their host genomes. Analysis
      of complete genome sequences have turned up numerous cases where TE sequences
      have been incorporated as exons into mRNAs, and it is widely assumed that such
      'exonized' TEs encode protein sequences. However, the extent to which TE-derived
      sequences actually encode proteins is unknown and a matter of some controversy.
      We have tried to address this outstanding issue from two perspectives: i-by
      evaluating ascertainment biases related to the search methods used to uncover TE
      derived protein coding sequences (CDS) and ii-through a probabilistic codon
      frequency based analysis of the protein coding potential of TE-derived exons.
      RESULTS: We compared the ability of three classes of sequence similarity search
      methods to detect TE-derived sequences among data sets of experimentally
      characterized proteins: 1-a profile-based hidden Markov model (HMM) approach, 2
      BLAST methods and 3-RepeatMasker. Profile based methods are more sensitive and
      more selective than the other methods evaluated. However, the application of
      profile-based search methods to the detection of TE-derived sequences among well
      curated experimentally characterized protein data sets did not turn up many more
      cases than had been previously detected and nowhere near as many cases as recent
      genome-wide searches have. We observed that the different search methods used
      were complementary in the sense that they yielded largely non-overlapping sets of
      hits and differed in their ability to recover known cases of TE-derived CDS. The
      probabilistic analysis of TE-derived exon sequences indicates that these
      sequences have low protein coding potential on average. In particular, non
      autonomous TEs that do not encode protein sequences, such as Alu elements, are
      frequently exonized but unlikely to encode protein sequences. CONCLUSION: The
      exaptation of the numerous TE sequences found in exons as bona fide protein
      coding sequences may prove to be far less common than has been suggested by the
      analysis of complete genomes. We hypothesize that many exonized TE sequences
      actually function as post-transcriptional regulators of gene expression, rather
      than coding sequences, which may act through a variety of double stranded RNA
      related regulatory pathways. Indeed, their relatively high copy numbers and
      similarity to sequences dispersed throughout the genome suggests that exonized TE
      sequences could serve as master regulators with a wide scope of regulatory
      influence.

PMID- 18036259
TI  - Differential intracellular distribution of DNA complexed with polyethylenimine
      (PEI) and PEI-polyarginine PTD influences exogenous gene expression within live
      COS-7 cells.
AB  - BACKGROUND: Polyethylenimine (PEI) is one of the most efficient and versatile non
      viral vectors available for gene delivery. Despite many advantages over viral
      vectors, PEI is still limited by lower transfection efficiency compared to its
      viral counterparts. Considerable investigation is devoted to the modification of
      PEI to incorporate virus-like properties to improve its efficacy, including the
      incorporation of the protein transduction domain (PTD) polyarginine (Arg); itself
      demonstrated to facilitate membrane translocation of molecular cargo. There is,
      however, limited understanding of the underlying mechanisms of gene delivery
      facilitated by both PEI and PEI-bioconjugates such as PEI-polyarginine (PEI-Arg)
      within live cells, which once elucidated will provide valuable insights into the
      development of more efficient non-viral gene delivery vectors. METHODS: PEI and
      PEI-Arg were investigated for their ability to facilitate DNA internalization and
      gene expression within live COS-7 cells, in terms of the percentage of cells
      transfected and the relative amount of gene expression per cell. Intracellular
      trafficking of vectors was investigated using fluorescent microscopy during the
      first 5 h post transfection. Finally, nocodazole and aphidicolin were used to
      investigate the role of microtubules and mitosis, respectively, and their impact
      on PEI and PEI-Arg mediated gene delivery and expression. RESULTS: PEI-Arg
      maintained a high cellular DNA uptake efficiency, and facilitated as much as 2
      fold more DNA internalization compared to PEI alone. PEI, but not PEI-Arg,
      displayed microtubule-facilitated trafficking, and was found to accumulate within
      close proximity to the nucleus. Only PEI facilitated significant gene expression,
      whereas PEI-Arg conferred negligible expression. Finally, while not exclusively
      dependent, microtubule trafficking and, to a greater extent, mitotic events
      significantly contributed to PEI facilitated gene expression. CONCLUSION: PEI
      polyplexes are trafficked by an indirect association with microtubules, following
      endosomal entrapment. PEI facilitated expression is significantly influenced by a
      mitotic event, which is increased by microtubule organization center (MTOC)
      associated localization of PEI polyplexes. PEI-Arg, although enhancing DNA
      internalization per cell, did not improve gene expression, highlighting the
      importance of microtubule trafficking for PEI vectors and the impact of the Arg
      peptide to intracellular trafficking. This study emphasizes the importance of a
      holistic approach to investigate the mechanisms of novel gene delivery vectors.

PMID- 18036260
TI  - Immunohistochemical identification of primary peritoneal serous
      cystadenocarcinoma mimicking advanced colorectal carcinoma: a case report.
AB  - Primary peritoneal cystadenocarcinoma is a rare tumor of similar histogenic
      origin as primary ovarian carcinoma. We present a case of primary peritoneal
      serous cystadenocarcinoma mimicking advanced colorectal cancer in a 68 yr-old
      African American female. Radiology, endoscopy and cytology yielded only
      inconclusive findings. Immunohistochemical analysis of percutaneously obtained
      ascitic fluid provided a correct diagnosis of primary peritoneal
      cystadenocarcinoma. The discovery of serous ascites at the time of laparotomy
      confirmed a diagnosis of primary peritoneal serous cystadenocarcinoma. Final
      surgical pathology reconfirmed the diagnosis of primary peritoneal
      cystadenocarcinoma. This case demonstrates the utility of immunohistochemistry
      for accurately diagnosing patients with inconclusive findings in the setting of
      peritoneal carcinomatosis and primary peritoneal cystadenocarcinoma.

PMID- 18036261
TI  - Primary breast lymphoma in the right breast during treatment for left breast
      cancer.
AB  - BACKGROUND: Primary breast lymphoma is a rare condition, and distinguishing it
      from breast cancer is important because their treatments differ radically.
      Moreover, a recent report showed that mastectomy offered no benefit in the
      treatment of primary breast lymphoma. CASE PRESENTATION: A 59-year-old woman was
      treated with adjuvant chemotherapy and local radiation after surgery for left
      breast cancer. She presented with a rapidly growing mass in the right breast at
      20 months after surgery. Mammography and computed tomography revealed a massive
      tumour. She was diagnosed with primary breast lymphoma by aspiration cytology,
      and surgery was performed. Histopathological and immunohistochemical findings
      confirmed a diffuse large B-cell type primary breast lymphoma. CONCLUSION: In
      this case, the lymphoma exhibited rapid growth despite chemotherapy for a
      malignancy in the contralateral breast. The patient had developed bronchiolitis
      obliterans organizing pneumonia due to radiation. Therefore, surgical treatment
      of the lymphoma was selected.

PMID- 18036264
TI  - An uncommon presentation and course of metastatic malignant melanoma: a case
      report.
AB  - Most patients with brain metastases from malignant melanoma are diagnosed after
      treatment for known extracranial metastases and have a poor outcome despite
      various local and systemic therapeutic approaches. Here we discuss an unusual
      case where a 45-year old patient presented with a brain metastasis as the first
      symptom of disease and where the presumed primary lesion later was found in the
      gastro-intestinal tract. Treatment consisted of sequential surgical removal of a
      total of 4 tumor sites (2 extracranially), whole-brain radiotherapy and two
      radiosurgery procedures within 13 months. Following her last treatment, the
      patient has now been in remission for 20 months. This case illustrates that some
      patients with multi-organ melanoma manifestations may benefit from the repeated
      use of effective local therapeutic approaches and may experience a quite
      favourable prognosis.

PMID- 18036263
TI  - Identification of BRCA1 missense substitutions that confer partial functional
      activity: potential moderate risk variants?
AB  - INTRODUCTION: Many of the DNA sequence variants identified in the breast cancer
      susceptibility gene BRCA1 remain unclassified in terms of their potential
      pathogenicity. Both multifactorial likelihood analysis and functional approaches
      have been proposed as a means to elucidate likely clinical significance of such
      variants, but analysis of the comparative value of these methods for classifying
      all sequence variants has been limited. METHODS: We have compared the results
      from multifactorial likelihood analysis with those from several functional
      analyses for the four BRCA1 sequence variants A1708E, G1738R, R1699Q, and A1708V.
      RESULTS: Our results show that multifactorial likelihood analysis, which
      incorporates sequence conservation, co-inheritance, segregation, and tumour
      immunohistochemical analysis, may improve classification of variants. For A1708E,
      previously shown to be functionally compromised, analysis of oestrogen receptor,
      cytokeratin 5/6, and cytokeratin 14 tumour expression data significantly
      strengthened the prediction of pathogenicity, giving a posterior probability of
      pathogenicity of 99%. For G1738R, shown to be functionally defective in this
      study, immunohistochemistry analysis confirmed previous findings of inconsistent
      'BRCA1-like' phenotypes for the two tumours studied, and the posterior
      probability for this variant was 96%. The posterior probabilities of R1699Q and
      A1708V were 54% and 69%, respectively, only moderately suggestive of increased
      risk. Interestingly, results from functional analyses suggest that both of these
      variants have only partial functional activity. R1699Q was defective in foci
      formation in response to DNA damage and displayed intermediate transcriptional
      transactivation activity but showed no evidence for centrosome amplification. In
      contrast, A1708V displayed an intermediate transcriptional transactivation
      activity and a normal foci formation response in response to DNA damage but
      induced centrosome amplification. CONCLUSION: These data highlight the need for a
      range of functional studies to be performed in order to identify variants with
      partially compromised function. The results also raise the possibility that
      A1708V and R1699Q may be associated with a low or moderate risk of cancer. While
      data pooling strategies may provide more information for multifactorial analysis
      to improve the interpretation of the clinical significance of these variants, it
      is likely that the development of current multifactorial likelihood approaches
      and the consideration of alternative statistical approaches will be needed to
      determine whether these individually rare variants do confer a low or moderate
      risk of breast cancer.

PMID- 18036265
TI  - Developing countries and neglected diseases: challenges and perspectives.
AB  - It is now commonly admitted that the so-called (most) neglected tropical
      diseases have been given little attention. According to World Health
      Organization, neglected diseases are hidden diseases as they affect almost
      exclusively extremely poor populations living in remote areas beyond the reach of
      health service. The European Parliament recognised that, to our shame, Neglected
      Diseases have not received the attention they deserve from EU actions. In the
      Millennium Development Goals they were given very little attention and mentioned
      just as other disease. Investing in drugs for these diseases is thought to be not
      marketable or profitable. However, despite their low mortality, neglected
      diseases are causing severe and permanent disabilities and deformities affecting
      approximately 1 billion people in the world, yielding more than 20 millions of
      Disability Adjusted Life Years (56.6 million according to Lancet's revised
      estimates) and important socio-economic losses. Urgent pragmatic and efficient
      measures are needed both at international and national levels.

PMID- 18036262
TI  - Reactive oxygen species and p47phox activation are essential for the
      Mycobacterium tuberculosis-induced pro-inflammatory response in murine microglia.
AB  - BACKGROUND: Activated microglia elicits a robust amount of pro-inflammatory
      cytokines, which are implicated in the pathogenesis of tuberculosis in the
      central nervous system (CNS). However, little is known about the intracellular
      signaling mechanisms governing these inflammatory responses in microglia in
      response to Mycobacterium tuberculosis (Mtb). METHODS: Murine microglial BV-2
      cells and primary mixed glial cells were stimulated with sonicated Mtb (s-Mtb).
      Intracellular ROS levels were measured by staining with oxidative fluorescent
      dyes [2',7'-Dichlorodihydrofluorescein diacetate (H2DCFDA) and dihydroethidium
      (DHE)]. NADPH oxidase activities were measured by lucigenin chemiluminescence
      assay. S-Mtb-induced MAPK activation and pro-inflammatory cytokine release in
      microglial cells were measured using by Western blot analysis and enzyme-linked
      immunosorbent assay, respectively. RESULTS: We demonstrate that s-Mtb promotes
      the up-regulation of reactive oxygen species (ROS) and the rapid activation of
      mitogen-activated protein kinases (MAPKs), including p38 and extracellular signal
      regulated kinase (ERK) 1/2, as well as the secretion of tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-6, and IL-12p40 in murine microglial BV-2 cells and
      primary mixed glial cells. Both NADPH oxidase and mitochondrial electron transfer
      chain subunit I play an indispensable role in s-Mtb-induced MAPK activation and
      pro-inflammatory cytokine production in BV-2 cells and mixed glial cells.
      Furthermore, the activation of cytosolic NADPH oxidase p47phox and MAPKs (p38 and
      ERK1/2) is mutually dependent on s-Mtb-induced inflammatory signaling in murine
      microglia. Neither TLR2 nor dectin-1 was involved in s-Mtb-induced inflammatory
      responses in murine microglia. CONCLUSION: These data collectively demonstrate
      that s-Mtb actively induces the pro-inflammatory response in microglia through
      NADPH oxidase-dependent ROS generation, although the specific pattern-recognition
      receptors involved in these responses remain to be identified.

PMID- 18036266
TI  - Too much of a good thing: the curse of overfeeding.
AB  - Enteral nutrition (EN) gives a legacy of under nutrition in intensive care
      patients but few appreciate that parenteral nutrition (PN) carries the other risk
      of overfeeding if used injudiciously. Over-feeding presents a significant
      metabolic stress but tight glycaemic control is now masking the traditional
      warning signs and does not on its own negate the need to give patients the right
      amount at the right time.

PMID- 18036268
TI  - Termites in the woodwork.
AB  - Termites eat and digest wood, but how do they do it? Combining advanced genomics
      and proteomics techniques, researchers have now shown that microbes found in the
      termites' hindguts possess just the right tools.

PMID- 18036269
TI  - Shaken not stirred: a global research cocktail served in Hinxton.
AB  - A report of the 2007 Cold Spring Harbor Laboratory/Wellcome Trust Conference on
      Functional Genomics and Systems Biology, Hinxton, UK, 10-13 October 2007.

PMID- 18036267
TI  - Clinical review: treatment of new-onset atrial fibrillation in medical intensive
      care patients--a clinical framework.
AB  - Atrial fibrillation occurs frequently in medical intensive care unit patients.
      Most intensivists tend to treat this rhythm disorder because they believe it is
      detrimental. Whether atrial fibrillation contributes to morbidity and/or
      mortality and whether atrial fibrillation is an epiphenomenon of severe disease,
      however, are not clear. As a consequence, it is unknown whether treatment of the
      arrhythmia affects the outcome. Furthermore, if treatment is deemed necessary, it
      is not known what the best treatment is. We developed a treatment protocol by
      searching for the best evidence. Because studies in medical intensive care unit
      patients are scarce, the evidence comes mainly from extrapolation of data derived
      from other patient groups. We propose a treatment strategy with magnesium
      infusion followed by amiodarone in case of failure. Although this strategy seems
      to be effective in both rhythm control and rate control, the mortality remained
      high. A randomised controlled trial in medical intensive care unit patients with
      placebo treatment in the control arm is therefore still defendable.

PMID- 18036270
TI  - Alveolar microstrain and the dark side of the lung.
AB  - Mechanical ventilation associated lung injury (VALI) negatively impacts the
      outcomes of critically ill patients. Research during the past two decades has led
      to a better understanding of key physiologic mechanisms of injury, yet
      uncertainty over the topographical distribution of these mechanisms continues to
      fuel controversies over "best ventilation practice" in injured lungs. In this
      issue Pavone and colleagues have explored the temporal and spatial evolution of
      VALI in an elegant use of intravital microscopy. Their findings reinforce the
      notion that regions which receive most of the inspired gas, in Pavone's case the
      non-dependent lung of a rat supported in the lateral decubitus posture, are
      particularly susceptible to injury. However, the inability to measure tissue
      strain remote from the pleura keeps important questions about small scale intra
      acinar stress and strain distributions unanswered.

PMID- 18036272
TI  - Genomics and premalignant breast lesions: clues to the development and
      progression of lobular breast cancer.
AB  - Advances in genomic technology have improved our understanding of the genetic
      events that parallel breast cancer development. Because almost all mammary
      carcinomas develop in the terminal duct lobular units of the breast,
      understanding the events involved in mammary gland development make it possible
      to recognize those events that, when altered, contribute to breast neoplasia. In
      this review we focus on lobular carcinomas, discussing the pathology,
      development, and progression of premalignant lobular lesions from a genomic point
      of view. We highlight studies utilizing genomic approaches and describe how these
      investigations have furthered our understanding of the complexity of premalignant
      breast lesions.

PMID- 18036273
TI  - Genes harbouring susceptibility SNPs are differentially expressed in the breast
      cancer subtypes.
AB  - Recently, genome-wide association studies of breast cancer revealed single
      nucleotide polymorphisms (SNPs) in five genes with novel association to
      susceptibility. While there is little doubt that the novel susceptibility markers
      produced from such highly powered studies are true, the mechanisms by which they
      cause the susceptibility remain undetermined. We have looked at the expression
      levels of the identified genes in tumours and found that they are highly
      significantly differentially expressed between the five established breast cancer
      subtypes. Also, a significant association between SNPs in these genes and their
      expression in tumours was seen as well as a significantly different frequency of
      the SNPs between the subtypes. This suggests that the observed genes are
      associated with different breast cancer subtypes, and may exert their effect
      through their expression in the tumours. Thus, future studies stratifying
      patients by their molecular subtypes may give much more power to classic case
      control studies, and genes of no or borderline significance may appear to be high
      penetrant for certain subtypes and, therefore, be identifiable.

PMID- 18036275
TI  - Effects of open heart surgery on hearing thresholds measured by high frequency
      audiometry.
AB  - BACKGROUND: The aim of this study was to investigate the differences between pre-
      and post-operative hearing thresholds, measured by high frequency audiometry, in
      patients undergoing open heart surgery. MATERIALS AND METHODS: Pre- and post
      operative audiometric assessments were performed in 20 patients undergoing open
      heart surgery. Pure tone audiometry testing was performed at 500, 1000, 2000,
      3000, 4000, 6000, 8000, 10 000, 12 000 and 14 000 Hz. We also evaluated:
      patients' clinical parameters (i.e. age, sex, diabetes mellitus, hypertension,
      hypercholesterolaemia, history of myocardial infarction, and whether undergoing
      coronary artery bypass surgery or valve surgery); various operative details
      (operative temperatures, cardiopulmonary bypass time and cross-clamp time); and
      post-operative clinical progress and its effect on hearing loss. RESULTS:
      Patients' pre- and post-operative pure tone audiometric results were
      significantly different at some frequencies (p < 0.05). In addition, there was a
      significant impact of hypertension, hypercholesterolaemia, history of myocardial
      infarction and cross-clamp time. CONCLUSIONS: This study shows that open heart
      surgery using cardiopulmonary bypass can lead to significant post-operative
      changes in hearing levels at some frequencies. Some additional patient parameters
      may influence this process. It seems possible that the risk of such hearing loss
      could be reduced; further studies may be able to define the significance of
      patients' concomitant disorders.

PMID- 18036274
TI  - Chromatin, gene silencing and HIV latency.
AB  - One of the cellular defenses against virus infection is the silencing of viral
      gene expression. There is evidence that at least two gene-silencing mechanisms
      are used against the human immuno-deficiency virus (HIV). Paradoxically, this
      cellular defense mechanism contributes to viral latency and persistence, and we
      review here the relationship of viral latency to gene-silencing mechanisms.

PMID- 18036276
TI  - Olfactory clearance: what time is needed in clinical practice?
AB  - OBJECTIVE: To determine olfactory adaptation and clearance times for healthy
      individuals, and to assess the effect of common variables upon these parameters.
      STUDY DESIGN AND SETTING: Fourteen healthy volunteers were recruited for a series
      of tests. Their initial olfactory threshold levels for phenethyl alcohol were
      determined. After olfactory exposure to a saturated solution of phenethyl alcohol
      (i.e. olfactory adaptation), the time taken for subjects to return to their
      initial olfactory threshold was then recorded (i.e. olfactory clearance). Visual
      analogue scale scores for subjective variables were also recorded. RESULTS: The
      14 subjects performed 120 tests in total. Despite consistent linear trends within
      individuals, olfactory clearance times varied widely within and between
      individuals. The mean olfactory clearance time for phenethyl alcohol was 170
      seconds (range 81-750). Univariate analysis showed a relationship between
      olfactory clearance times and age (p = 0.031), symptoms (p = 0.029) and mood (p =
      0.048). CONCLUSIONS: When testing a person's sense of smell in a clinical
      setting, recent exposure to similar smells should be noted, and a period of 15
      minutes needs to be allowed before retesting if using phenethyl alcohol. Other
      variables need not be controlled, but greater clearance time may be needed for
      older patients.

PMID- 18036277
TI  - Coblation tonsillectomy: a prospective, double-blind, randomised, clinical and
      histopathological comparison with dissection-ligation, monopolar electrocautery
      and laser tonsillectomies.
AB  - INTRODUCTION: Coblation tonsillectomy is a relatively recently introduced
      surgical technique which attempts to bridge the gap between 'hot' and 'cold'
      tonsillectomy methods. AIM: To compare coblation tonsillectomy with three
      commonly used surgical techniques: cold dissection-ligation, monopolar
      electrocautery and CO2 laser. MATERIALS AND METHODS: A prospective, randomised,
      double-blinded clinical trial was undertaken of 60 adult patients divided into
      three equal study groups. Patients in each group were randomly assigned to have
      one tonsil removed with coblation and the second with one of the other three
      tonsillectomy techniques. Ten randomly selected tonsils resected by each method
      were sent for histopathological evaluation. RESULTS: Coblation was significantly
      faster to perform than laser and produced significantly less intra-operative
      blood loss than both the dissection-ligation and laser techniques. Subjective
      visual analogue scale comparisons showed a non-significant pain score difference
      between coblation and dissection-ligation on most post-operative days. Coblation
      produced consistently highly significantly (p < 0.001) less pain, compared with
      electrocautery up to the 12th post-operative day and laser up to the 10th post
      operative day. There was no significant difference in tonsillar fossa healing,
      comparing coblation to both dissection-ligation and laser techniques. Monopolar
      electrocautery produced significantly slower healing than coblation after 7 post
      operative days, with no significant difference after 15 post-operative days.
      Histopathological evaluation showed that coblation inflicted significantly less
      thermal tissue injury than either electrocautery (p = 0.001) or laser (p =
      0.003). CONCLUSIONS: In adult patients, coblation tonsillectomy offers some
      significant advantages in terms of post-operative pain and healing, compared with
      other tonsillectomy techniques.

PMID- 18036278
TI  - A critical evaluation of the evidence on a causal relationship between
      Helicobacter pylori and otitis media with effusion.
AB  - OBJECTIVE: There is growing interest in the presence of Helicobacter pylori in
      the upper aerodigestive tract, and in the middle ear in patients with otitis
      media with effusion. Some studies have reported detecting H pylori in the middle
      ear, although reports to the contrary exist. In this study, we critically
      evaluate the evidence for the theory that H pylori in the middle ear plays a role
      in otitis media with effusion. MATERIAL: We undertook a systematic review of all
      available studies investigating the presence of H pylori in the middle ear of
      patients with otitis media with effusion. The current literature was critically
      analysed using the key words and phrases 'Helicobacter pylori' 'otitis media with
      effusion', 'serous otitis media', 'glue ear' and 'middle ear'. Six original
      research papers were identified, studying a total of 203 patients and 27
      controls; two of these papers were randomised, controlled studies and four were
      prospective, cohort studies. RESULTS: At present, there is poor evidence for the
      existence of H pylori-associated otitis media with effusion. CONCLUSIONS: Further
      research in the field is needed in order to delineate the presence of H pylori
      and its role in the pathogenesis of otitis media with effusion.

PMID- 18036279
TI  - Vestibular aqueduct in sudden sensorineural hearing loss.
AB  - OBJECTIVE: To evaluate the vestibular aqueduct in patients with sudden
      sensorineural hearing loss. METHODS: We evaluated 19 patients (12 men and seven
      women; age range, 22-79 years) with unilateral sudden sensorineural hearing loss,
      using computed tomography and magnetic resonance imaging. All these patients had
      unilateral sudden sensorineural hearing loss. We also evaluated 47 control
      subjects (22 men and 25 women; age range, 22-79 years). RESULTS: In sensorineural
      hearing loss affected ears, the width of the vestibular aqueduct at the midpoint
      and at the operculum was significantly greater than that in contralateral ears or
      in control ears. The width of the vestibular aqueduct at the midpoint and the
      operculum did not correlate with the audiometric threshold or the audiogram
      configuration. Contrast enhancement of the ipsilateral endolymphatic sac was
      observed in 17 of 19 patients with sudden sensorineural hearing loss (89 per
      cent). Eleven of these 17 patients also showed enhancement on the contralateral
      side, but no patient showed enhancement only on the contralateral side. In
      sensorineural hearing loss affected ears, the width of the vestibular aqueduct
      did not differ significantly between those patients with and without enhancement.
      CONCLUSIONS: The vestibular aqueducts of sudden sensorineural hearing loss
      affected ears are wider than those of controls. Precise imaging and evaluation of
      the inner ear is essential when investigating the pathological conditions
      responsible for sudden sensorineural hearing loss.

PMID- 18036280
TI  - Securing a nasopharyngeal airway.
AB  - OBJECTIVE: The nasopharyngeal airway is a simple airway adjunct used by various
      healthcare professionals. It is the least invasive method of safely managing
      upper airway obstruction. The objective of this report was to describe a rapid
      and very simple method of securing a nasopharyngeal airway in an agitated
      patient. METHOD: We describe a simple method of securing a nasopharyngeal airway,
      using safety pins and tapes. RESULT: This technique has been used by the authors
      in several emergency situations and has been found to be quick and effective.
      CONCLUSION: The nasopharyngeal airway is a simple piece of equipment that is
      cheap and easy to use. The technique described in this article is a simple,
      practical and effective method of securing a nasopharyngeal airway in an
      emergency situation.

PMID- 18036281
TI  - Branula used as T-tube introducer for middle-ear effusion.
AB  - OBJECTIVE: We report a method of inserting a T-tube. METHOD: A 14-G branula and a
      T-tube are used. RESULTS: This method was found to be simple and required few
      instruments. CONCLUSIONS: To the best of our knowledge, this method has not
      previously been reported.

PMID- 18036282
TI  - Ketamine in the management of generalised cephalic tetanus.
AB  - BACKGROUND: Tetanus is a fatal infection caused by the neurotoxin tetanospasmin
      released by the vegetative spores of Clostridium tetani. The high mortality rate
      is related to frequent tetanic fits with laryngeal spasm and airway obstruction.
      Numerous anticonvulsants are in use, with varying efficacy in controlling fits.
      This case report highlights the use of ketamine as adjunctive therapy in the
      management of tetanus. CASE REPORT: A 20-year-old woman was admitted with a
      history of recurrent left ear pain, with bloody, purulent discharge, following a
      self-inflicted injury. She developed tetanic spasms 24 hours after admission. She
      had received no immunisations. A tracheostomy was established to relieve airway
      obstruction, and ketamine was added to the medication when breakthrough seizures
      were refractory to diazepam. CONCLUSION: Ketamine is of proven safety as an
      anaesthetic agent, especially in cases in which an anaesthetist is not readily
      available. Its effectiveness in this case, in combination with diazepam, warrants
      further evaluation.

PMID- 18036283
TI  - Safe, complete resection of epiglottic cysts with phono-ultra-microsurgical
      technique.
AB  - Generally, epiglottic cysts have been treated by the puncture technique or
      surgical resection. However, these techniques can result in accidental injury to
      the cyst wall. As a result, the contents of the cyst may spread throughout the
      larynx, trachea and pharyngeal cavity. The ideal treatment would involve complete
      resection without cyst perforation. We use a completely different approach for
      the resection of epiglottic cysts, with successful results, which we term the
      advanced phono-ultra-microsurgical technique. One difference between this method
      and previous techniques of surgical epiglottic cyst resection is that the cyst is
      sealed off before resection in order to prevent rupture and spread of its
      contents. To enable this, we have developed a special device to facilitate
      suturing of the vocal fold epithelium, utilising a knot-pusher. This suturing
      technique allows complete removal of epiglottic cysts. Our technique allows
      optimal prevention of cyst rupture and spread of contents.

PMID- 18036284
TI  - Parapharyngeal abscess in a previously tonsillectomised child with periodic
      fever, aphthous stomatitis, pharyngitis and adenitis syndrome: first reported
      case.
AB  - OBJECTIVE: We present the first reported case of parapharyngeal abscess in a
      child with periodic fever, aphthous stomatitis, pharyngitis and adenitis
      syndrome, an uncommon syndrome of recurrent, self-limiting fever in children.
      METHOD: Case report and review of the literature to date concerning periodic
      fever, aphthous stomatitis, pharyngitis and adenitis syndrome. RESULTS: Periodic
      fever, aphthous stomatitis, pharyngitis and adenitis syndrome is an incompletely
      understood syndrome which requires careful and thorough investigation in order to
      distinguish it from other causes of recurrent fever. There has been much recent
      debate in the literature over the merits of various treatment strategies,
      including tonsillectomy. CONCLUSION: To the authors' knowledge, this is the first
      reported case of a parapharyngeal abscess in a child with periodic fever,
      aphthous stomatitis, pharyngitis and adenitis syndrome, made more significant by
      the fact that the child had undergone tonsillectomy one year prior. This case
      provides evidence that tonsillectomy does not protect against one of the more
      serious complications of oropharyngeal infection in children with this syndrome.

PMID- 18036285
TI  - Isolated fracture of the manubrium of the malleus.
AB  - OBJECTIVE: To describe a series of five patients with isolated fracture of the
      manubrium of the malleus. DESIGN: Retrospective case series. SUBJECTS: Five
      patients aged 44-64 years with isolated fracture of the manubrium who presented
      to our institution over a five-year period (2000-2005). RESULTS: All patients
      presented with a history of digitally manipulating the external auditory canal,
      leading to the manubrial fracture, which we presume was due to a suction-type
      mechanism. Otomicroscopy often revealed a break in the smooth contour of the
      manubrium. All patients had air-bone gaps on audiometry, especially at higher
      frequencies. Tympanometry showed hypermobility of the tympanic membrane in four
      patients who were tested. Laser-Doppler vibrometry revealed increased umbo
      velocity in four out of five patients. Four patients were treated conservatively.
      One patient underwent exploratory tympanotomy with successful ossiculoplasty.
      CONCLUSIONS: Isolated fracture of the manubrium is a rare condition which may
      present as sudden-onset hearing loss after digital manipulation of the external
      auditory canal. The diagnosis can be made on the basis of otomicroscopy,
      audiometry, tympanometry and laser-Doppler vibrometry. Conservative treatment is
      often successful.

PMID- 18036288
TI  - [Current status of research on the myocardial protection during open heart
      surgery].

PMID- 18036287
TI  - The impact of esophageal candidiasis on hospital charges and costs across patient
      subgroups.
AB  - OBJECTIVE: Assess the impact of esophageal candidiasis on US hospital inpatient
      charges, length of stay (LOS), and costs across clinically relevant subgroups.
      METHODS: Total hospital charge (THC) and LOS data extracted from the 2005
      National Inpatient Sample (NIS) were compared for patients with and without
      esophageal candidiasis within the top 20 most commonly assigned Diagnosis Related
      Groups (DRGs) for the disease. Total hospital costs were estimated using hospital
      charges in the 2005 Medicare Provider Analysis and Review (MEDPAR) file and
      hospital cost-to-charge ratios published in the Center for Medicare and Medicaid
      Service's (CMS) 2005 Inpatient Prospective Payment System Standardization File.
      RESULTS: Across 274 DRGs, 45 727 esophageal candidiasis patients were identified.
      Mean age was 50.8 years; 52.5% were female, 59.3% Caucasian. Median LOS was 7
      days; median THC was $25 649. Of all esophageal candidiasis cases identified, 65%
      fell into the top 20 most commonly assigned DRGs. Within this subset, HIV-related
      DRGs accounted for 22% of the esophageal candidiasis cases. The difference in
      mean THC and LOS for esophageal candidiasis patients in HIV-related DRGs was not
      significant. However, total hospital costs were higher for esophageal candidiasis
      patients in this subset ($11 886 vs. $10 534, p < 0.01). The remaining 78% of
      esophageal candidiasis cases were assigned to 19 non-HIV-related DRGs. Mean LOS,
      THC, and total hospital costs were significantly higher for esophageal
      candidiasis patients within these 19 non-HIV-related DRGs, (8.4 vs. 6.1; $35 704
      vs. $23 874, and $10 917 vs. $7474, p < 0.01 in all cases). CONCLUSIONS:
      Esophageal candidiasis affects a wide range of patient groups; it increases LOS
      and total charges within non-HIV-related hospitalizations. Although the costs
      presented in this study are estimates, they do suggest a significant increase in
      cost among esophageal candidiasis cases. Future studies on treatment and
      preventive care strategies for esophageal candidiasis should not be limited to
      HIV patients, but instead performed across a wider range of disease settings.

PMID- 18036286
TI  - A systematic review of the effectiveness of rivastigmine for the treatment of
      behavioral disturbances in dementia and other neurological disorders.
AB  - BACKGROUND: Dementia is frequently associated with behavioral disturbances, some
      of which have a significant impact on patient quality of life and the likelihood
      of institutionalization. Cholinergic systems, among other neurotransmitters in
      the brain, appear to be involved with different behaviors, such as psychosis,
      depression, agitation, and personality changes. SCOPE: This paper reviews the
      clinical data on the effectiveness of rivastigmine, a dual inhibitor of
      acetylcholinesterase and butyrylcholinesterase, in ameliorating behavioral
      disturbances in different patient populations. Relevant articles were identified
      through MEDLINE searches with no date restrictions. FINDINGS: In particular,
      rivastigmine has shown efficacy in treating behavioral disturbances in patients
      with a wide range of dementias - Alzheimer's disease, vascular dementia, fronto
      temporal dementia, mixed dementia, Lewy body dementia, Parkinson's disease with
      dementia, and schizophrenia with dementia. Most of the studies have been open
      label clinical trials with behavior as a secondary endpoint. The behavior domains
      that most consistently showed improvement were apathy/indifference, anxiety,
      delusions (psychosis), and hallucinations. The major limitation of this review is
      that the effects on behavioral symptoms were usually secondary endpoints in
      clinical trials. CONCLUSION: The efficacious effects of treatment with
      rivastigmine on various behavioral disturbances provide supporting evidence that
      cholinergic mechanisms, among other neurotransmitters, are involved in the
      manifestation of some behavioral and psychological symptoms of dementia.

PMID- 18036289
TI  - [Further improve the understanding of hand, foot and mouth disease].

PMID- 18036290
TI  - [Cardioprotective effects of propofol and midazolam in children with congenital
      heart diseases undergoing open heart surgery].
AB  - OBJECTIVE: To observe the cardioprotective effects of propofol and midazolam in
      children with congenital heart diseases undergoing open heart surgery. METHODS:
      Thirty-two children with cyanotic congenital heart diseases of ASA classes I - II
      were randomly divided into 2 equal groups: propofol combined with low dose
      fentanyl group (Group PF) and midazolam combined with low dose fentanyl group
      (Group MF). The changes of hemodynaics, ECG, SpO2, nasopharyngeal and rectal
      temperatures were monitored continuously. The time of tracheal extubation and ICU
      staying time were recorded. Venous blood samples were collected when the venous
      channel was opened (T(0)), 2 h after declamping of the aorta (T(4)), and 24 h
      after operation (T(5)) to detect the plasma cardiac troponin I (cTnI). Myocardium
      samples were collected 10 - 20 min after aorta cross-clamp (T(2)), and 10 - 20
      min after declamping of the aorta (T(3)) to undergo immunohistochemistry to
      observe the expression of heme oxygenase-1 (HO-1). RESULTS: The tracheal time of
      Group GF was 14.17 h, significantly shorter than that of Group MF (23.65 h, P <
      0.05), and the ICU staying time of Group GF was 30.17 h, significantly shorter
      than that of Group MF (49.47 h, P < 0.05). The plasma cTnI level at T(4) of Group
      GF was 97 ng/ml +/- 33 ng/ml, significantly higher than those at T(0) (0.17 ng/ml
      +/- 0.10 ng/ml, P < 0.01) and T(5) (23 ng/ml +/- 13 ng/ml, P < 0.01). The plasma
      cTnI level at T(4) of Group MF was138 ng/ml +/- 56 ng/ml, significantly higher
      than those at T(0) (0.62 ng/ml +/- 0.96 ng/ml, P < 0.01) and T(5) (24 ng/ml +/- 6
      ng/ml, P < 0.01). And the plasma cTnI levels at T(5) of these 2 groups were both
      significantly higher than those at T(0) (both P < 0.01), however, there was no
      significant difference in the plasma cTnI level at any time point between these 2
      groups. The grey values of HO-1 in cardiac muscle cells at T(2) of Groups GF and
      MF were 182.2 +/- 0.8 and 193.5 +/- 1.4, both significantly higher than those at
      T(3) (125.6 +/- 2.1 and 145.5 +/- 7.4 respectively, both P < 0.01), and the grey
      values of HO-1 in cardiac muscle cells at T(2) and T(3) of Group MF were both
      significantly higher than those of Group GF (both P < 0.05). CONCLUSION: Both
      propofol and midazolam have protective effects for the children with congenital
      heart diseases undergoing open heart surgery, and propofol is superior to
      midazolam in the cardioprotection.

PMID- 18036291
TI  - [Adenosine preconditioning reduces myocardial injury in patients undergoing off
      pump coronary artery bypass grafting surgery].
AB  - OBJECTIVE: To evaluate the effects of adenosine on reducing myocardial injuries
      in patients undergoing off-pump coronary artery bypass grafting (OPCAB). METHODS:
      Forty patients undergoing OPCAB were allocated into two equal groups randomly:
      adenosine (ADO) group and control group. The patients in the ADO group were given
      infusion of adenosine through the central venous catheter via internal jugular
      vein when the surgeons dissociated the internal mammary artery. The initial
      infusion rate was 50 microg.kg(-1).min(-1), the infusion speed increased every
      minute until the dose of 150 microg.kg(-1).min(-1), and the total duration of
      adenosine infusion lasted for 10 min. The patients of the control group received
      intravenous infusion of 0.9% saline instead during the infusion period. 5 min
      after the completion of adenosine or saline infusion protocol, revascularization
      began. Blood samples were collected at following time points: T0 (10 minutes
      after anesthesia), T1, T2, T3, T4, and T5 (30 minutes, and 2, 6, 12, and 24 hours
      after revascularization respectively). Levels of MB isoenzyme of creatine kinase
      (CK-MB) and cardiac troponin I (cTnI) were measured. RESULTS: The CK-MB levels of
      the control group increased from T1 to T5 (all P < 0.05), and the CK-MB level of
      the ADO group increased only at T2 (P < 0.05), however, the level of CK-MB 24 h
      after revascularization of the control group was significantly higher than that
      of the ADO group (P < 0.05). The cTnI level increased significantly after
      revascularization (from T1 to T5) in both group (all P < 0.05), and the cTnI
      levels of the control group were higher than those of the ADO group at all time
      points, and were significantly higher at T4 and T5 points (both P < 0.05).
      CONCLUSION: OPCAB can cause myocardial injuries which can be reduced by adenosine
      preconditioning through the reduction of the release of CK-MB and cTnI.

PMID- 18036292
TI  - [Myocardial protective effect of Shenfu injection in patients undergoing valve
      replacement].
AB  - OBJECTIVE: To investigate the myocardial protective effect of Shenfu injection in
      patients undergoing valve replacement. METHODS: Forty patients undergoing valve
      replacement surgery under cardio-pulmonary bypass (CPB) were randomly divided
      into two equal groups: group C (control group, given with 4:1 blood containing
      cardioplegic liquid during the CPB) and group SF (Shenfu injection, receiving the
      blood containing cardioplegic liquid with 20 ml/L of Shenfu injection
      additionally). Blood samples were withdrawn from the central vein before
      operation, 30 minutes after aorta declamping, and 4, 12, and 24 hours after CPB,
      to test the serum cardiac troponin I (cTnI), creatine phosphokinase (CK), and
      creatine phosphokinase isoenzyme (CK-MB). RESULTS: The CK, CK-MB, and cTnI level
      were normal before operation and there were no significant differences in these
      indexes between the two groups. 30 minutes after aorta declamping, the CK, CK-MB,
      and cTnI levels were higher than those before operation in both groups (P < 0.05,
      P < 0. 01), and the higher levels remained to 24 hours after CPB. 24 hours after
      CPB, the CK level of the group SF was significantly lower than that of the group
      C (P < 0.05), and 30 minutes after aorta declamping to 24 h after CPB, the CK-MB
      and cTnI levels were lower in the group SF compared with the group C (all P < 0.
      05). CONCLUSION: Shenfu injection decreases the level of CK, CK-MB and cTnI, and
      reduces the myocardial injury.

PMID- 18036293
TI  - [Cardioprotective effects of cariporide as an adjunct in different cardioplegic
      solutions: an experiment with rabbits].
AB  - OBJECTIVE: To investigate the cardioprotective effects of cariporide as an
      adjunct in different cardioplegic solutions. METHODS: The hearts of 32 young New
      Zealand rabbits were isolated, hung on the Langendorff perfusion apparatus,
      arrested with 4 degrees C cardioplegic solutions to cause cardiac ischemia for
      120 min, reperfused with 37 degrees C Krebs-Henseleit solution, and randomly
      divided into 4 equal groups: St. Thomas cardioplegic solution group (perfused
      with St. Thomas cardioplegic solution every 30 min), histidine-tryptophane
      ketoglutarate (HTK) cardioplegic solution group (perfused with HTK solution, St.
      Thomas solution + cariporide (St + C) group (perfused with St. Thomas
      cardioplegic solution plus cariporide), and HTK solution plus cariporide (HTK +
      C) group (perfused with HTK cardioplegic solution plus cariporide). Multichannel
      physiological record instrument was used to record the left ventricular
      functions: left ventricular diastolic pressure (LVDP), maximum change rate of
      left ventricular systolic pressure rise and fall (+dp/dt(max)), maximum change
      rate of left ventricular diastolic pressure rise and fall (-dp/dt(max)), and
      coronary flow (CF). Automatic biochemical analyzer was used to measure the
      creatine kinase (CK)-MB, Then the level of ATP in the cardiac muscle cells was
      detected by high pressure liquid chromatography, the content of malonyldialdehyde
      (MDA) was detect by sulfur barbituric acid method. The calcium content (iCa) was
      measured by atomic absorption spectrophotometry. And the myocardial water content
      (WC) was measured too. RESULTS: The LVDP, +dp/dt(max), -dp/dt(max), CF recovery
      rate, and ATP content of the HTK group were all significantly higher than those
      of the St. Thomas group (all P < 0.05), and the CK-MB, MDA, WC, and iCa of the
      HTK group were all significantly lower than those of the St. Thomas group (all P
      < 0.05). The ATP level of the HTK + C group was significantly higher than those
      of the HTK and St + C groups (both P < 0.05), and the CK-MB, WC, MDA, and iCa of
      the HTK + C group were all lower than those of the HTK and St + C groups (all P <
      0.05). The MDA level of the St + C group was significantly higher than that of
      the HTK group, and the ATP of the St + C group was significantly lower than that
      of the HTK group (both P < 0.05), however, there was no significant differences
      in CK-MB, WC, and iCa between these 2 groups (all P > 0.05). CONCLUSION:
      Cariporide enhances the cardioprotective effects of the St. Thomas and HTK
      cardioplegic solutions in immature myocardium.

PMID- 18036294
TI  - [Identification of DYT1 mutation in patients with primary torsion dystonia
      patients in China].
AB  - OBJECTIVE: To evaluate the value of denaturing high-performance liquid
      chromatography (DHPLC) in detection of mutations in the DYT1 gene in the patients
      with primary torsion dystonia (PTD) and to explore the distribution of mutation
      in China. METHODS: Peripheral blood samples were collected from 13 early PTD
      patients, 8 males and 5 females, aged 20 +/- 6. PCR was used to amplify the exon
      5 of the DYT1 gene. The mutations were identified by DHPLC and DNA sequencing.
      RESULTS: A 3 bp (GAG) deletion mutation in the exon 5 of the DYT1 gene resulting
      in Glu302del was found in 5 patients. The result of DHPLC was consistent with
      that of PCR-RFLP. There was not any mutation in other sites of the DYT1 gene.
      CONCLUSION: DHPLC technique is an effective tool for detecting 3 bp deletion
      mutation in the DYT1 gene. The GAG (3 bp) deletion in the DYT1 gene may play an
      important role in causing early-onset and generalized dystonia in China.

PMID- 18036295
TI  - [Anticoagulation treatment in real-life practice of patient with nonvalvular
      atrial fibrillation in Beijing city].
AB  - OBJECTIVE: To assess the anticoagulation treatment in real-life practice for
      nonvalvular atrial fibrillation (AF) in Beijing. METHODS: A questionnaire survey
      was conducted among 583 patients with nonvalvular AFF, 327 males and 256 females,
      aged 40 - 93, selected randomly from 8 general hospitals (n = 375, 64.3%) and 7
      community health service centers (n = 208, 35.7%) located in the 8 districts in
      Beijing city, mainly from the out-patient departments (n = 437, 75%). RESULTS:
      110 of the 583 patients (18.9%) were prescribed warfarin in which the percentage
      of international normalized ratio (INR) range (2.0 - 3.0) was 39.1% (n = 43).
      68.2% of them had taken warfarin for less than one year. Another 33 patients
      (5.7%) had ever taken warfarin. 346 patients (59.3%) took aspirin of which 85.7%
      were exposed to the dose of 76 - 150 mg/d, and no one was administered the dose
      of 325 mg/d. 18.9% of the 583 patients had not received any anticoagulation or
      antiplatelet drugs. 78.6% of patients had never got the advice about taking
      warfarin from their doctors, and over 75% of the patients lacked in knowledge
      about the necessity of anticoagulation treatment for AF patients. The prevalence
      of stroke in the total 583 patients was 22.8%, 22.0% in those receiving warfarin
      treatment, 24.3% in those receiving aspirin treatment, and 21.3% in those
      receiving neither anticoagulation treatment nor antiplatelet treatment, without
      significant differences among them (chi(2) = 1.09, P = 0.58). CONCLUSION: The
      percentage of taking anticoagulation treatment in real-life practice pf the AF
      patients in Beijing is lower than that of taking antiplatelet treatment. The
      period of anticoagulation treatment is short and the effect is not good. The
      percentage of taking aspirin is too high in the high risk patients of stroke, but
      the dose of aspirin is on the low side. Doctors' advice and knowledge related to
      anticoagulation treatment of the patients are important factors influencing the
      anticoagulation treatment.

PMID- 18036296
TI  - [Comparative analysis of the inter-observer reliability and intra-observer
      reproducibility between Lenke and PUMC classification systems for adolescent
      idiopathic scoliosis].
AB  - OBJECTIVE: To compare the intra-observer reproducibility and inter-observer
      reliability regarding the results of Lenke's and Peking Union Medical College
      (PUMC) classification systems for adolescent idiopathic scoliosis (AIS). METHODS:
      Five spine surgeons independently measured the X ray films of 62 AIS patients
      using both Lenke and PUMC classification systems. Three weeks later, the spine
      surgeons repeated the same classification process. No measurement trace was
      allowed to be left on the X ray films. SAS software was used to calculate the
      Kappa values and analyze the intra-observer reproducibility and inter-observer
      reliability RESULTS: The overall reliability and reproducibility rates of the
      Lenke classification system were 69.8% (Kappa value = 0.675) and 74.2% (Kappa
      value = 0.690) respectively, in which the curve characteristic parameter
      reliability and reproducibility rates were 86.5% (Kappa value = 0.808) and 87.4%
      (Kappa value 0.826) respectively, the lumbar correction reliability and
      reproducibility rates were 95.2% (Kappa value = 0.919) and 94.5% (Kappa value =
      0.908) respectively, and the sagittal thoracic correction reliability and
      reproducibility rates were 85.2% (Kappa value = 0.734) and 89.0% (Kappa value =
      0.805 respectively). The reliability and reproducibility rates of the PUMC
      classification system were 91.0% (Kappa value = 0.896) and 90.2% (Kappa value =
      0.892) respectively. CONCLUSION: The reliability and reproducibility rates of the
      Lenke classification system were better than the previously reported results.
      However, the PUMC classification system expresses better reliability and
      reproducibility. The PUMC classification system is relatively easier with fewer
      curve types, hence leading to less divergence among the clinicians. Comparing to
      the classifications used in the past, both classification systems have the
      advantages of correctly categorizing AIS according to its individual traits, as
      well as accurately examining the X ray results, hence achieving significance in
      terms of surgical outcome and design.

PMID- 18036297
TI  - [Gene expression of insulinlike growth factor-I in the osteophyte development].
AB  - OBJECTIVE: To investigate the gene expression and potential function of
      insulinlike-Iin osteophyte development. METHODS: Specimens were obtained from 25
      individuals undergoing total knee arthroplasty due to severe primary
      osteoarthritis and from 3 healthy adults. The tissue samples were embedded in
      paraffin wax and made into sections to undergo HE and toluidine blue staining.
      Immunohistochemistry was used to detect the expression of collagen I, IIa, IIb,
      and X. The osteophytic tissues were grouped into different types based on the
      results by histomorphology and expression of different collagens and
      glycosaminoglycans. Immunohistochemistry and in situ hybridization were used to
      detect the expression of insulinlike growth factor-I in the osteophyte. The
      images obtained by imunohistochemistry and in situ hybridization were put into
      the image analysis system to be analyzed semi-quantitatively. RESULTS: Based on
      the characteristics of histomorphology and expression of different collagens and
      glycosaminoglycans, the osteophytic tissues were grouped into five different
      types. The type I tissue mainly consists of mesenchymal fibroblast-like cells
      producing collagen I. The type II tissue was characterized by the existence of
      collagen IIA expressed in prechondrocyte and glycosaminoglycans in the
      extracellular mesenchyma. he type III tissue was marked by the co-expression of
      collagen IIB, glycosaminoglycans, collagen IIA, and collagen I. The type IV
      tissue showed a clear zonal organization of chondrocytes, abundant expression of
      collagen IIB and glycosaminoglycans, and hypertrophic deep chondrocytes
      expressing Collagen X. The type V tissue had a composition similar to that of the
      normal articular hyaline cartilage with a predominance of collagen IIB and
      abundant glycosaminoglycans. These five types seemed to indicate the different
      stages of osteophyte development: mesenchymal cell, prechondrocyte, chondrocyte,
      early osteophyte and mature osteophyte. Immunohistochemistry showed that the
      expression level of insulinlike growth factor-I in the type I tissue was 14.6 +/-
      3.8, significantly higher than those in the types IV and V tissues (7.7 +/- 3.5
      and 6.0 +/- 1.9 respectively, both P = 0.000); and the expression level of
      insulinlike growth factor-I in the type II tissue was 13.6 +/- 4.7, significantly
      higher than those in the types IV and V tissues (both P = 0.000). The results of
      in situ hybridization were similar to those by imunohistochemistry. CONCLUSION:
      Insulinlike growth factor-I mRNA is mainly expressed in the early stage
      osteophyte, and it may play an important role in initiation of the chondrogenic
      differentiation of mesenchymal progenitor cells in the early stage of osteophyte
      development.

PMID- 18036298
TI  - [Time of early death after cervical spinal cord injury].
AB  - OBJECTIVE: To investigate the distribution of time of early death in the patients
      with cervical spinal cord injury (CSCI). METHODS: The clinical data of 63 CECI
      patients, including demographics, mechanism of injury, cervical spinal cord
      injury level and severity, associated injury, radiographs, management, and the
      causes of death, the time from injury to hospitalization and the time from injury
      to death were retrospectively analyzed so as to detect the time and cause of
      early death. RESULTS: The 63 CDCI patients died in early stage. 27 of the 63
      patients (42.8%) died within a week after CSCI; 43 patients (68.3%) died within
      two weeks after CSCI, 57 patients (90.5%) died within four weeks after CSCI, and
      6 patients (9.5%) died after four weeks after CSCI. CONCLUSION: The peak time of
      death is a week after CSCI. The major time of death is two weeks after CSCI.
      90.5% cases died within four weeks. Respiratory failure is the leading cause of
      early death in patients with CSCI.

PMID- 18036299
TI  - [The effects of blood motilin and gastrin on electrical activity and emptying of
      the intrathoracic stomach after esophagectomy for cancer].
AB  - OBJECTIVE: To observe the effects of blood motilin and gastrin on the electrical
      activity and emptying of the intrathoracic stomach after esophagectomy for
      cancer. METHODS: Electrogastrography and determination of blood motilin and
      gastrin were carried out in 52 subjects, including 20 normal volunteers and 32
      esophageal cancer patients before and 1, 3, 6, 12 months after operation. Gastric
      emptying of radiopaque granula was studied in 35 of the 52 subjects, including 5
      normal volunteers, 7 preoperative patients and 23 postoperative patients.
      RESULTS: The preoperative gastric emptying of radiopaque granula was 28.0 +/- 8.0
      pieces 120 second after eating the test meal, significantly less than that of the
      normal controls [(38.0 +/- 2.0) pieces, t = 3.515, P = 0.006], and decreased to
      (16.0 +/- 4.8) pieces one month after esophagectomy (t = 6.987, P = 0.000), and
      then recovered to 16.8 +/- 4.8 one year after surgery but still could not reach
      normal (t = 9.387, P = 0.0000). Compared with the normal controls, the amplitude
      of electrogastrogram (EGG) of the preoperative patients was (229 +/- 118) microv,
      not significantly different from that of the controls [(226 +/- 62) microv, t =
      0.085, P = 0.933], and the frequency of EGG of the preoperative patients was (3.1
      +/- 0.2) times per minute, not significantly different from that of the controls
      too [(3.2 +/- 0.1) times per minute, t = 0.872, P = 0.387]. But the frequency and
      amplitude of EGG of the patients one month after operation were (2.9 +/- 0.3)
      times per minute and (172 +/- 46) microv respectively, both significantly
      decreased in comparison with those of the normal controls (t = 2.336, P = 0.024;
      and t = 3.118, P = 0.003). The amplitude reached normal [(223 +/- 60) microv, t =
      0.145, P = 0.885] 1 year after surgery, but the frequency still remained at a low
      level [(3.0 +/- 0.1) times per minute, t = 2.208, P = 0.033). The level of blood
      motilin of the preoperative patients was (488 +/- 197) ng/L, significantly higher
      than that of the controls [(248 +/- 98) ng/L, t = 5.030, P = 0.000], and the
      blood gastrin level of the preoperative patients was (26 +/- 15) ng/L,
      significantly higher than that of the controls [(20 +/- 12) ng/L, t = 2.741, P =
      0.043]. One year after operation the blood motilin level maintained at a high
      level [(443 +/- 129) ng/L, t = 3.725, P = 0.001], and the gastrin level remained
      at a high level too [(48 +/- 23) ng/L, t = 3.703, P = 0.001]. CONCLUSION:
      Physiologically important, persistent elevation of blood gastrin and motilin in
      the patients who underwent esophagectomy for cancer facilitates the recovery of
      electrical activity and emptying of the intrathoracic stomach.

PMID- 18036300
TI  - [Value of thyroid transcription factor-1 in identification of the prognosis of
      bronchioloalveolar carcinoma].
AB  - OBJECTIVE: To study the expression and clinical significance of cytokeratin
      subtypes CK7 and CK20 and thyroid transcription factor-1 (TTF-1) in
      bronchioloalveolar carcinoma (BAC), and to investigate the value of these factors
      in identification of the prognosis of BAC. METHODS: Eighty-one specimens of BAC
      resected during operation, 68 of non-mucinous type and 13 of mucinous type,
      underwent immunohistochemical examination to detect the expression of CK7, CK20,
      and TTF-1. The value of these 3 factors in the identification of the prognosis of
      BAC was examined by survival analysis. RESULTS: All specimens showed positive
      expression of CK7, CK20, and TTF-1. There was no significant differences in CK7
      expression rate among different ages, clinical stages, and pathological subtypes
      (all P > 0.05). Compared with that in the BAC of stage III and that of BAC of non
      mucinous type, the CK20 positive rates of the BAC of stage I - II and mucinous
      type were both significantly higher (chi(2) = 3.928, P < 0.05, and chi(2) =
      11.512, P < 0.05). The TTF-1 positive rates of the BAC of stage III and
      nonmucinous type were significantly higher than those of stage I - II and
      mucinous type respectively (chi(2) = 7.840, P < 0.05, and chi(2) = 19.497, P <
      0.05). There was a statistically significant positive correlation between the
      expression of CK7 and expression of TTF-1 (r = 0.257, P = 0.021). Univariate
      analysis showed that the main prognostic factors were TTF-1 expression (P =
      0.017), clinical stage (P = 0.000), tumor diameter (P = 0.017) and N stage (P =
      0.000). Strata analysis suggested that in the nonmucinous type BAC patients the
      survival time of those positive for TTF-1 expression was superior to those
      negative for TTF-1 (P = 0.009); and in the stage III BAC patients the survival
      time of those positive for TTF-1 was superior to those negative for TTF-1 (P =
      0.022). Cox regression analysis suggested that TTF-1 (P = 0.035), TNM stage (P =
      0.000), tumor diameter (P = 0.034), and N stage (P = 0.000) were independent
      factors affecting the prognosis. CONCLUSION: There is a statistically significant
      positive correlation between the expression of CK7 and the expression of TTF-1.
      TTF-1 and CK20 provide a new evidence for the molecular staging of BAC. TTF-1,
      TNM stage, tumor diameter and N stage are all independent factors affecting the
      prognosis of BAC.

PMID- 18036301
TI  - [Treatment of chronic and painful vertebral compressive fractures with
      vertebroplasty in senior patients].
AB  - OBJECTIVE: To evaluate the efficiency of treatment of chronic and painful
      compressive fractures of vertebral bodies with vertebroplasty in senior patients.
      METHODS: 98 patients of chronic and painful compressive fractures of vertebral
      bodies suffering from severely back pain and activity of daily living, 33 males
      and 65 females, aged 71 +/- 12, with the average medical history of 12 months,
      underwent vertebroplasty. Follow-up was conducted for 3 - 40 months. Six-point
      Behavioral Rating Scale and Activity of Daily Living (ADL) Scale were used to
      evaluate the efficacy. RESULTS: 123 affected compressive vertebral bodies in the
      98 cases were treated with vertebroplasty. After 3.5 - 7 ml of bone cement was
      injected into the lesions, complete relief was got in 20 cases, obvious relief
      was achieved in 59 cases, improvement was made in 14 cases, and no progress was
      seen in 5 case. The score of 6-point Behavioral Rating Scale decreased from 4.2
      +/- 1.1 before vertebroplasty to 1.2 +/- 0.9 (P < 0.01). The ADL score decreased
      from 4.2 +/- 1.1 before vertebroplasty to 1.9 +/- 0.6 (P < 0.01). CONCLUSION:
      Vertebroplasty significantly improves the painful symptoms and ability of daily
      life in senior patients with chronic painful vertebral compressive fractures.

PMID- 18036303
TI  - [Clinical study of standardized tertiary rehabilitation program in promoting
      upper and lower limbs motor function in stroke patients].
AB  - OBJECTIVE: To investigate the effect of standardized tertiary rehabilitation
      (STR) on the upper and lower limbs' motor function in the patients with cerebral
      stroke accompanied by hemiplegia. METHODS: 1365 patients with cerebral stroke
      accompanied by hemiplegia enrolled sequentially from 22 hospitals were classified
      into two groups: cerebral infarction group and hemorrhage group, and then
      randomly subdivided into two groups: test group (n = 688, administered with STR
      in addition to routine interventions of neurological medicine) and control group
      (n = 677, given the routine interventions). All patients were assessed with the
      scale of Modified Fugl-Meyer Motor Assessment (M-FMMA) at the time of enrollment
      and 1, 3, and 6 months after the stroke respectively. The evaluation was blind on
      the part of the physician. RESULTS: At each of the following post-stroke
      checkpoints, the scores of the functions in the cerebral infarction or hemorrhage
      test group were higher than those in the control (P < 0.01). The M-FMMA scores at
      the enrollment, and 1, 3, and 6 months after stroke of the cerebral infarction
      patients in the test group were 28, 47, 65, and 75 respectively, and the M-FMMA
      scores at the enrollment, and 1, 3, and 6 months after stroke of the cerebral
      infarction patients in the control group were 26, 37, 48, and 55 respectively.
      The M-FMMA scores at the enrollment, and 1, 3, and 6 months after stroke of the
      cerebral hemorrhage patients in the test group were 23, 44, 67, and 80
      respectively, and the M-FMMA scores at the enrollment, and 1, 3, and 6 months
      after stroke of the cerebral hemorrhage patients in the control group were 21,
      32, 46, and 55 respectively. During the STR, the scores of functional improvement
      of both the cerebral infarction and hemorrhage test groups were higher than those
      of the control groups (both P < 0.01). By the end of the 6th month after stroke,
      the scores of functional improvement of both the cerebral infarction and
      hemorrhage test groups went up by 47 and 56 respectively for the 2 test groups,
      while went up by 29 and 34 respectively for the 2 control groups. Compared with
      the control groups, the score of functional improvement of the cerebral
      infarction test group was 18 points higher, and that of the cerebral hemorrhage
      test group was 22 points higher. CONCLUSION: STR significantly improves the
      neurological function in the patients with cerebral strokes accompanied by
      hemiplegia.

PMID- 18036304
TI  - [Distribution and differentiation of marrow mesenchymal cells in tumor tissue:
      experimental with rabbits].
AB  - OBJECTIVE: To study the distribution of bone marrow mesenchymal stem cells (MSCs)
      in tumor tissue and the possibility of MSCs differentiating into myofibroblast
      under the induction of local tumor microenvironment. METHODS: MSC were isolated
      from 24 New Zealand rabbits, and cultured. Then vx-2 tumor tissue was
      transplanted under the bladder mucosa of each animal. Then the rabbits were
      randomly divided into 2 equal groups: control group and test group. One week
      after the transplantation, the autologous F2 passage MSCs marked by diamino
      phenyl-indole (DAPI) were transplanted into the tumor tissue of the test group
      and DMEM medium was infused into the tumor tissue of the control group.
      Ultrasonography was performed 1, 2, 3, and 4 week(s) after the vx-2 tumor mass
      was transplanted. The maximum bladder tumor diameters of each animal were
      recorded and the mean value of each group was calculated. One animal in each
      group with its tumor diameter closest to the average value of the very group was
      put to death in the third week and all the left animals were killed in the fourth
      week to observe the tumor development. Another rabbit underwent same treatment as
      that in the test group was put to death to observe the distribution of MSCs in
      the tumor tissue one week after self-MSC transplantation. Immunofluorescence was
      used to trace the MSCs in the tumor tissue. Double labeling immunofluorescence
      for alpha-smooth muscle actin (alpha-SMA) and vimentin was performed to identify
      whether MSCs could differentiate into myofibroblasts. RESULTS: Ultrasonography
      showed no tumor mass one week after the vx-2 tumor mass transplantation. In the
      second week, the mean maximum tumor diameter of the control group was 0.70 +/-
      0.14 cm, not significantly different from that of the test group (0.78 +/- 0.14
      cm, t = 1.308, P = 0.204), however, the mean maximum tumor diameter in the third
      and fourth weeks of the control group were 1.8 +/- 0.4 cm and 2.3 +/- 0.6 cm
      respectively, both significantly shorter than those of the test group (2.2 +/-
      0.3 cm and 3.8 +/- 0.9 cm respectively, both P < 0.05). Microscopy showed that
      MSCs were distributed uniformly in the tumor tissue one week after
      transplantation while most of the MSCs were distributed in the tumor stroma three
      weeks after transplantation. Double labeling immunofluorescence showed an
      increase of alpha-SMA and vimentin expression three weeks after MSC engraftment.
      CONCLUSION: MSCs are initially distributed uniformly in the tumor tissue and then
      distributed mainly in the tumor stroma. Furthermore, MSCs accelerate tumor
      development and can differentiate into myofibroblasts under the induction of
      tumor microenvironment.

PMID- 18036305
TI  - [Restoration of pathological changes of emphysema by angiogenesis factors:
      experiment of rats].
AB  - OBJECTIVE: To investigate whether intratracheal administration of basic
      fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF)
      restore the pulmonary function and pathology in emphysema, and research the
      mechanism of they restored pulmonary emphysema, and the pathogenesis of pulmonary
      emphysema. METHODS: Twenty-four Wistar rats were randomized into the 4 equal
      groups: bFGF group [receiving a single intratracheal instillation of porcine
      pancreatic elastase (PPE) 250 U/kg, and 4 weeks later receiving intratracheal
      instillation of bFGF 400 U once a week for 3 weeks), VEGF group (receiving a
      single intratracheal instillation of PPE 250 U/kg, and 4 weeks later receiving
      intratracheal instillation of VEGF 2 microg once a week for 3 weeks), control
      group [receiving a single intratracheal instillation of PPE 250 U/kg, and 4 weeks
      later receiving intratracheal instillation of normal saline (NS) once a week for
      3 weeks], and normal group (receiving intratracheal instillation of NS in above
      mentioned pattern). Four weeks after treatment, arterial blood sample was
      collected from the abdominal aorta to undergo blood gas analysis for assessment
      pulmonary function, and then the rata were killed with their lungs taken out to
      undergo pathological examination. Immunohistochemistry was performed to detect
      the CD34, markers of pulmonary capillary endothelial cells. RESULTS: There were
      no significant differences in the artery blood gas analysis among the four groups
      (all P > 0.05). The levels of mean alveoli number (MAN) of the bFGF and VEGF
      groups were (43 +/- 8)/HP and (44 +/- 9)/HP] respectively, both significantly
      higher than that of the control group [(30 +/- 6)/HP, both P < 0.01]. The levels
      of mean linear intercept (MLI) of the bFGF and VEGF groups were (196 +/- 38)
      microm and (194 +/- 38) microm respectively, both significantly lower than that
      of the control group [(288 +/- 68) microm, both P < 0.01). the mean alveoli area
      (MAA) level of the bFGF and VEGF groups were (9856 +/- 1864) microm(2) and (9804
      +/- 1929) microm(2) respectively, both significantly lower than that of the
      control group [(14,525 +/- 3408) microm(2), both P < 0.01]. The percentages of
      CD34(+) cells of the bFGF and VEGF groups were (3.7 +/- 1.3)% and (2.6 +/- 1.2)%
      respectively, both significantly higher than that of the control group [(0.8 +/-
      0.7)%, both P < 0.05). CONCLUSION: bFGF and VEGF can restore the pathological
      changes of experimental emphysema. The damage of pulmonary capillary may play an
      important role in the pathogenesis of pulmonary emphysema.

PMID- 18036306
TI  - [Effects of short hair RNA on the expression of SMN1 gene in human mesenchymal
      stem cells].
AB  - OBJECTIVE: To construct a plasmid expressing short hairpin RNA (shRNA) targeting
      SMN1 gene in mammalian cells and to investigate the effect of shRNA on the
      expression of SMN1 gene in human mesenchymal stem cells (hMSCs), thus providing
      experimental basis for the establishment of SMA cell model. METHODS: Five shRNAs
      targeting SMN1 gene was designed according to the SMN1 cDNA sequence provided by
      GenBank, and cloned to the downstream of U6.1 promoter in the pRNAT-U6.1/Neo
      vector, thus forming different recombinant plasmids: pshRNA-SMN1, pshRNA-SMN2,
      pshRNA-SMN3, pshRNA-SMN4, and pshRNA-SMN5 expressing specific shRNAs targeting
      SMN1 gene. The plasmid psh-RNA-0 was used as controls. The recombinant plasmid
      pshRNA-SMN1 was transfected into human mesenchymal stem cells (hMSCs) by
      Lipofectomine (TM) 2000, and its effects on the mRNA expression and protein
      expression of fl-SMN were observed by RT-PCR and Western blotting. RESULTS: The
      successful construction of recombinant plasmid pshRNA-SMN was identified by
      enzyme cutting and DNA sequencing. After transfection, the expression levels of
      fl-SMN mRNA and protein in hMSCs of the pshRNA-SMN1-1 group and pshRNA-SMN1-4
      group were significantly lower than that of the control group (both P < 0.05)
      with an interfering efficiency of 64.05% and 61.04% in mRNA level, and 52.97% and
      61.57% in protein level respectively. However, the expression of Delta7-SMN mRNA
      was not effected. CONCLUSION: The constructed recombinant plasmid called pshRNA
      SMN1 inhibits the expression of fl-SMN mRNA and protein in hMSCs efficiently.

PMID- 18036310
TI  - [Clinical practice guidelines: objectivity and standardization].

PMID- 18036312
TI  - [Relationship between autoantibodies and HLA-DQ genotypes in patients with type 1
      diabetes mellitus].
AB  - OBJECTIVE: To explore the relationship between the 3 islet autoantibodies, i.e.,
      glutamic acid decarboxylase antibody (GADA), protein-tyrosine-phosphatase-2
      autoantibody (IA-2A), and insulin autoantibody (IAA), and human leukocyte HLA-DQ
      genotypes in the patients with type 1 diabetes mellitus (T1DM). METHODS:
      Peripheral blood samples were collected from 495 T1DM patients and 376 healthy
      controls. Radioligand assay was used to detect the levels of GADA and IA-2A.
      Seventy-one of the 495 T1DM patients with insulin treatment less than 14 days
      underwent radioligand assay to measure the IAA level. 338 TIDM patients,
      including 187 antibodies-positive and 151 antibodies-negative patients, and 278
      healthy controls underwent PCR and sequencing so as to examine the genetic
      polymorphism of HLA-DQ. RESULTS: (1) The frequencies of DQA1*03-DQB1 *0303,
      DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 haplotypes in the T1DM patients were
      32.6%, 14.1% and 10.2% respectively, all significantly higher than those in the
      controls (21.9%, 3.5%, and 2.9% respectively, all P < 0.01), however, the
      frequency of DQA1*0102-DQB1*0602 haplotype in the T1DM patients was 1.7%,
      significantly lower than that in the controls (5.3%, P < 0.05). (2) The GADA
      positive rates of in the T;DM patients with DQA1*05-DQB1*0201 or DQA1*03
      DQB1*0401 haplotype were 55.8% and 65.5% respectively, both significantly higher
      than those of the T1DM patients without DQA1*05-DQB1*0201 or DQA1*03-DQB1*0401
      haplotype (41.0% and 40.3%, respectively P < 0.05 or P < 0.01), and the IA-2A
      positive rate of the T1DM patients with DQA1*03-DQB1*0303 haplotype was 27.0%,
      significantly higher than that of the T1DM patients without DQA1*03-DQB1*0303
      haplotype (7.9%, P < 0.01), there were no significant differences in GADA and IA
      2A positivity between the T1DM patients with and without DQA1*03-DQB1*0302
      haplotype (48.5% vs 43.9% and 24.2% vs 15.4%, both P > 0.05). The GADA positivity
      rate of the T1DM patients with DQA1*0102-DQB1 *0602 haplotype was 16.7%,
      significantly lower than those patients without DQA1*0102-DQB1 *0602 haplotype
      (45.9%, P < 0.05). There was no significant difference in IAA level between those
      patients with and without susceptible DQ alleles and haplotypes (P > 0.05).
      CONCLUSION: GADA is associated with HLA-DQA1*05-DQB1*0201 and DQA1*03-DQB1*0401
      haplotypes, and IA-2A is associated with DQA1*03-DQB1 *0303 haplotype.

PMID- 18036313
TI  - [Quantitative assessment of healthy People's cardiovascular aging and analysis of
      the relevant law: study in three cities in Northern China].
AB  - OBJECTIVE: To quantitatively assess the progress of cardiovascular aging in the
      healthy people in North China by non-invasive ways, and to analyze the law of
      cardiovascular aging. METHODS: 855 healthy people randomly sampled from 3 cities
      in northern China: Shenyang, Dalian, and Beijing, divided into 4 age groups: < or
      = 44, 45 - 59, 60 - 74, and > or = 75, underwent interview of the life style and
      dietary structure, measurement of blood pressure, heart and carotid
      ultrasonography, blood biochemistry, blood routine, urine routine, and detection
      of micro-inflammation indexes such as C-reactive protein, fibrinogen (FIB),
      thrombomodulin, and interleukin-6. Totally 70 items were surveyed. Then the
      cardiovascular aging assessment equation was constructed and cardiovascular
      biological aging score (CBAS) was calculated to analyze the law of cardiovascular
      aging. RESULTS: Seven items including pulse pressure, carotid artery intimal
      medial thickness, carotid artery end-diastolic velocity, mitral valve anulus
      anterior wall A, mitral valve anulus lateral wall E, FIB, total cholesterol were
      correlated with chronological age significantly (r = 0.63, 0.54, -0.41, 0.45, 
      0.42, 0.43, and 0.46, all P < 0.01). The CBAS was positively correlated with
      chronological age (r = 0.85, P < 0.05) with the most rapid change rate in the
      group aged 45 - 59. CONCLUSION: CAS can be used as an objective index to
      quantitatively assess the cardiovascular aging. With an acceleration of
      cardiovascular aging rate after the age 45, the speed of cardiovascular aging in
      healthy people may be inconstant. The age 45 - 59 may be the key threshold for
      cardiovascular aging.

PMID- 18036314
TI  - [The effect of single nucleotide polymorphism SNP + 45 of the adiponectin gene on
      the rosiglitazone maleate response in patients with type 2 diabetes].
AB  - OBJECTIVE: To investigate the effect of single nucleotide polymorphism (SNP) + 45
      of the adiponectin (ADIPOQ) gene on the response to therapy with rosiglitazone
      maleate in patients with type 2 diabetes. METHODS: A total of 103 newly diagnosed
      type 2 diabetes patients without taking any drug were enrolled and treated with
      rosiglitazone maleate (4 or 8 mg/d) for 24 weeks. On scheduled time phenotype
      measured were height, weight, waist, hip; blood pressure; HbA1c; plasma glucose
      level, serum insulin level, serum proinsulin level of blood obtained at 0, 2, 4
      and 6 minute during arginine stimulation test; serum lipid level including total
      cholesterol, triglyceride, high-density and low-density lipoprotein cholesterol.
      Response to the rosiglitazone maleate therapy was defined by both a > or = 20%
      decrease in fasting plasma glucose and a > or = 15% decrease in HbA1c values
      after 24 weeks of rosiglitazone maleate treatment. All patients were genotyped
      for the ADIPOQ SNP + 45 by PCR-RFLP. RESULTS: (1) Of the 103 patients, the
      frequencies of TT, TG and GG genotypes of ADIPOQ SNP + 45 were 0.55, 0.36 and
      0.09 respectively. The T allele frequency and G allele frequency were 0.73 and
      0.27 respectively. (2) There was a significant difference in the response rate to
      rosiglitazone maleate treatment between the TT genotype and the TG + GG genotype
      (P = 0.0295). Response rate of the TG + GG genotype (56.41%) was higher than that
      of the TT genotype (33.93%). Furthermore, multivariate Logistic regression
      analysis revealed that SNP + 45 of ADIPOQ gene and HbA1c were the independent
      risk factors for rosiglitazone maleate treatment response. (3) After 24 weeks of
      treatment period, the FPG, 2hPG, HbA1c and HOMA-IR were significantly decreased
      in comparison with pre-treatment in both genotype groups. (4) The change in the
      clinical parameters after 24 weeks of treatment period showed no significant
      difference between the SNP + 45 of ADIPOQ gene. CONCLUSION: SNP + 45 of ADIPOQ
      gene is associated with the response rate to rosiglitazone maleate treatment in
      patients with type 2 diabetes and may be the major determinant of response rate.
      The response rate of the TG + GG genotype is higher than that of the TT genotype.

PMID- 18036315
TI  - [Correlation between the function of monocytes/macrophages and disease
      progression in people living with HIV/AIDS in several provinces in China].
AB  - OBJECTIVE: To investigate the functional states of peripheral blood
      monocytes/macrophages and their relation with the disease progression in people
      living with HIV/AIDS (PWHA). METHODS: Peripheral blood samples were collected
      from 57 PWHA who didn't receive antivirus treatment before and 32 healthy
      controls in Jilin, Liaoning, and Henan provinces. Flow cytometry was used to
      detect the expression of the early activation molecule CD69 in the CD14(+) cells.
      The plasma HIV RNA level was determined using real-time PCR. RESULTS: The CD69
      expression rate in the CD14(+) T cells of the PWHA group was 27% +/- 4%,
      significantly higher than that of the controls (P < 0.01). The CD69 expression
      rate of the AIDS group was 39% +/- 3%, significantly higher than those of the HIV
      group and long-term nonprogressors (LTNP) group (26% +/- 3% and 20% +/- 4%
      respectively, both P < 0.05), that of the HIV groups being significantly higher
      than that of the LTNP group too (P < 0.05). The side scatter value of the CD14(+)
      T cells of the PWHA group was 76 +/- 16, significantly higher than that of the
      control group (50 +/- 12, P < 0.05). The monocyte/macrophage CD69 expression rate
      was significantly negatively correlated with the absolute value of CD4(+) T cells
      (r = -0.872, P < 0.01), and not correlated with the value of CD8(+) T cells (P >
      0.05). The monocyte/macrophage CD69 expression rate was significantly positively
      correlated with the HIV-1 RNA viral load (r = 0.697, P < 0.01). CONCLUSION: The
      activation and the phagocytosis function of the monocytes/macrophages of the PWHA
      in China are higher than those of the healthy control. They are positively
      correlated with the disease progression.

PMID- 18036316
TI  - [Vasculogenic mimicry in the bi-directional differentiation malignant tumors of
      digestive tract].
AB  - OBJECTIVE: To investigate whether vasculogenic mimicry (VM) exists in the bi
      directional differentiation malignant tumors of digestive tract. METHODS: 111
      specimens of bi-directional differentiation malignant tumors of digestive tract.
      including malignant gastrointestinal stromal tumors (GIST, n = 80), malignant
      melanoma (n = 18), and carcinosarcoma (n = 13), underwent periodic acid Schiff
      (PAS) staining and microscopy. Immunohistochemistry was used to examine the
      expression of vascular endothelial growth factor (VEGF), and CD31. Microvascular
      density (MVD) and vasculogenic mimicry density (VMD) were calculated. RESULTS:
      PAS-positive patterned matrix-associated vascular channels with red blood cells
      therein were detected in 39.1% (31.5/111) of the tumor samples. (89 +/- 20) and
      MVD (47 +/- 12) both lower than without VM (76, 126 +/- 18, 78 +/- 13, all P <
      0.05) the expression levels of VEGF and MVD in the tumors containing patterned
      channels were (89 +/- 20) and MVD (47 +/- 12) respectively, both significantly
      lower than those in the tumors without VM [(126 +/- 18) and (78 +/- 13)
      respectively, both P < 0. 05]. The higher the malignant degree of tumor, the
      higher the proportion of the tumor with VM. The levels of MVD and VMD of the
      GIST, malignant melanoma, and carcinosarcoma with low malignancy were 45 +/- 19,
      15 +/- 8, and 38 +/- 25 respectively, all significantly lower than those of the
      GIST, malignant melanoma, and carcinosarcoma with high malignancy (128 +/- 42, 81
      +/- 17, 122 +/- 39, all P < 0.05). CONCLUSION: VM exists in the bi-directional
      differentiation malignant tumors of digestive tract. The tumor cells obtain blood
      supply and become metastatic via the mechanism of VM.

PMID- 18036317
TI  - [Detection of JAK2V617F mutation in patients with myeloproliferative disorders
      with TaqMan-MGB probe].
AB  - OBJECTIVE: To develop a novel platform for detection of the JAK2V617F mutation in
      patients with myeloproliferative disorders (MPD) by real-time quantitative PCR.
      METHODS: TaqMan-MGB probe was constructed. Peripheral blood samples were
      collected from 374 MPD patients, 76 with polycythemia vera (PV), 38 with chronic
      myelogenous leukemia (CML), and 115 with essential thrombocythemia (ET), and 19
      with idiopathic myelofibrosis (IMF). Peripheral blood samples from 65 patients
      with acute myelogenous leukemia (AML), 30 patients with acute lymphoblastic
      leukemia, 8 patients with chronic lymphoblastic leukemia, and 7 patients with non
      Hodgkin's lymphoma and 16 cases of normal donor bone marrow were used as
      controls. Genomic DNA or RNA was extracted and reversely transcrtibed into cDNA.
      TaqMan-MGB probe was used to detect the JAK2V617F mutant in MPD. Furthermore, 168
      specimens underwent allele specific PCR and 8 specimens underwent sequencing.
      This method was used on both DNA and cDNA specimens from 38 MPD patients
      simultaneously so as to test the consistency. RESULTS: The JAK2V617F mutation
      rates of the PV, ET, and IMF patients were 53 (70%), 59 (51%), (58%)
      respectively. JAK2V617F mutation was found in only one of the 65 AML patients and
      was not identified in other control specimens. Both the results of allele
      specific PCR and of sequencing were consistent with the result of TaqMan-MGB
      probe method. CONCLUSION: JAK2V617F mutation is widespread in Chinese MPD
      patients. Real-time quantitative PCR with TaqMan MGB probe can be used for rapid
      and accurate detection of the JAK2V617F mutation.

PMID- 18036318
TI  - [The trend of clinical characteristics and prognosis of women's breast cancer
      1981 - 2000].
AB  - OBJECTIVE: To investigate the trend of clinical characteristics and prognosis of
      breast cancer in women during the past 2 decades (1981 - 2000). METHODS: 1678
      cases were sampled randomly from the 11400 breast cancer patients who were
      hospitalized in Tianjin Medical University Cancer Hospital 1981 - 2000.
      Retrospective analysis of the clinical characteristics and prognosis between
      different eras was conducted. RESULTS: The numbers of hospitalized female breast
      cancer patients during the periods 1981 - 1985, 1986 - 1990, 1991 - 1995, 1996 -
      2000 were 209, 316, 449, and 704 respectively with an increase of 237% within 20
      years and an annual increase rate of 11.8%. The mean onset age remained 46 - 47.
      The detection rate of breast cancer at early stages (stages 0 approximately I)
      was 15.5% during 1996 - 2000, higher than that during 1981 - 1985 (12%), and the
      detection rate of breast cancer at stage III during 1996 - 2000 was 16.5%, lower
      than that during 1981 - 1985 (24.9%). The proportion of carcinoma in situ during
      1996 - 2000 was 4.4%, higher than that during 1981 - 1985 (3.7%). The axillary
      lymph node positive rate during 1996 - 2000 was 46.3%, lower than that during
      1981 - 1985 (51.8%s), and the local recurrence/distance metastasis rate during
      1996 - 200 was 13.5%, lower than that during 1981 - 1985 (27.8%). The 5-year and
      10-year survival rates during 1996 - 2000 were 86% and 74%, both higher than
      those during 1981 - 1985 (76% and 63% respectively). CONCLUSION: During the past
      2 decades, the incidence of breast cancer shows an uptrend. The proportion of
      early stage breast cancer increases gradually and the proportion of axillary
      lymph node positive rate and metastasis rate show a downtrend. The prognosis of
      the breast cancer patients has been improved during these periods.

PMID- 18036319
TI  - [Expression and purification of epitope peptide of human tyrosinase and its
      antigenicity in vitiligo patients].
AB  - OBJECTIVE: To express the epitope peptide of human tyrosinase (TYR), and discuss
      the application of the peptide in detecting autoantibody of the vitiligo
      patients. METHODS: The epitope areas 240 - 255, 289 - 294, 295 - 300, 435 - 447,
      and 461 - 479 of human TYR were synthesized and connected to the vector pGEM-T.
      The target gene was cloned to the prokaryotic expression vector pGEX-4T-2, which
      was then transferred to Escherichia coli BL21 host cells. Isopropy-beta-D
      thiogalactoside (IPTG) was used to induce the protein expression that was
      examined with SDS-PAGE and Western blotting. Indirect ELISA was conducted to
      detect the antigenicity of the peptide in 100 blood specimens of active vitiligo
      patients and 30 healthy controls. RESULTS: The recombinant expression vector was
      constructed successfully. The SDS-PAGE and Western blotting results showed
      expression of the recombinant protein in E. coli. The amount of the recombinant
      protein reached about 70% of the total mass of bacterial protein with PAGE
      analysis system. With the glutathione S-transferase (GST) purification kit, the
      purity of recombinant protein reached over 90%. Indirect ELISA showed that
      reaction with the target protein was negative in all the 30 healthy controls and
      was positive in 64 of the 100 active vitiligo patients. CONCLUSION: The epitope
      peptide of human TRY is expressed successfully, and it has antigenicity in the
      serum of vitiligo patients.

PMID- 18036320
TI  - [Simultaneous modulated accelerated radiation therapy in the treatment of
      nasopharyngeal cancer].
AB  - OBJECTIVE: To evaluate the toxicity and clinical efficacy of simultaneous
      modulated accelerated radiation therapy (SMART) technique for nasopharyngeal
      carcinoma. METHODS: 110 patients with nasopharyngeal carcinoma underwent boost
      treatment with SMART at the dose of 2.5 Gy/time for 28 times for gross tumor
      volume (GTV) with the total dose of 70 Gy and the dose of 2.0 Gy/time once a day
      and 5 times a week, totally 28 times, with the total dose of 56 Gy for the
      clinical treatment volume (CTV). The GTV dose for 36 of these patients was
      boosted to 80 Gy. Follow-up was conducted for 24 months (7 - 44 months). RESULTS:
      Follow-up showed that the 1, 2, and 3-year survival rates were 97.02%, 88.72%,
      and 78.27%, respectively. The 1 - 3 year local relapse-free survival rate was
      97.94% (95.10% - 100%). The 1, 2, and 3-yea local-regional relapse-free rates and
      distant metastasis-free rates were 95.21%, 89.83%, 76.10% and 95.38%, 85.71%, and
      79.67%, respectively. According to the Fuzhou staging, the 3-year overall
      survival rate of the stage I - II patients was 100%, while the 3-year survival
      rate of the stage III patients was 74.33% and the 3-year survival rate of stage
      IV a patients was 62.96%. The acute toxicity was well tolerated except for the
      high incidence of severe mucositis. No grade 4 side effects occurred. Most of the
      patients showed Grade 0 to 1 late toxicity and xerostomia was a common side
      effect. No increase of toxicity was seen when the GTV dose was increased to 80
      Gy. CONCLUSION: SMART yields superior dose distribution over the traditional
      radiotherapy in nasopharyngeal carcinoma at the early or advanced stages. The
      local-regional control was excellent and distant metastasis remains the main
      risk. Dose escalation to 80 Gy was safe and feasible. Toxicity of SMART is
      acceptable and tolerable.

PMID- 18036321
TI  - [Immunologically-competent cells in liver infiltrating lymphocytes in patients
      with chronic severe hepatitis B].
AB  - OBJECTIVE: To investigate the frequencies of immunologically competent cells
      (ICCs) in the liver-infiltrating lymphocytes (LILs) and peripheral blood and
      their possible role in pathogenesis in patients with chronic severe hepatitis B
      (CSHB). METHODS: LILs were isolated from the liver tissue samples from 11 CSHB
      patients and 5 normal controls (NCs) by the method of combined grinding with semi
      frosted microscopic slides and sedimentation of hepatic cells. The frequency of
      isolated ICCs, including CD3(+), CD4(+), and CD8(+) T-cells, NK cells, NKT cells,
      and B cells was examined and compared with that of the circulating ICCs in the
      CSHB patients. Comparison was conducted between the CSHB patients and the
      controls. RESULTS: (1) In the CSHB patients, the frequencies of CD4(+) T cells
      and B cells in LILs were 17% +/- 6% and 3.0% +/- 1.0% respectively, both
      significantly lower than those in the circulating blood (32% +/- 8% and 21.4% +/-
      12.2% respectively, both P < 0.01); however, the frequencies of CD8(+) T cells,
      NK cells, and NKT cells in LILs were 38% +/- 13%, 34% +/- 18%, and 10% +/- 4%
      respectively, all significantly lower than those in the circulating blood (26% +/
      6%, 15% +/- 9%, and 6% +/- 4%, all P < 0.05). (2) The frequencies of
      infiltrating CD3(+) T cells and CD4(+) T cells of the CSHB patients were both
      significantly higher than those of the NCs (P = 0.042 and P = 0.001); and the
      frequency of infiltrating CD8(+) T cells of the CSHB patients was higher than
      that of the NCs, and the and the frequencies of infiltrating NK cells and NKT
      cells in LILs were lower than those of the NCs, however, not significantly. (3)
      Compared with the liver tissues from the NCs, the liver tissues from the CSHB
      patients exhibited a significantly higher ratio of liver-infiltrating CD4(+) T
      cells to peripheral blood CD4(+) T-cell subsets (P = 0.001), and significantly
      lower ratios of liver-infiltrating NKT cells and B cells to the peripheral blood
      NKT-cells and B cells (P = 0.029 and P = 0.001 respectively). CONCLUSION: The
      abundant infiltrating immune active cells, especially the CD4(+) T cells, CD8(+)
      T cells, and NK cells, may be the causal factors that drive the progressive
      development of CSHB.

PMID- 18036322
TI  - [An study on screening the gene clusters associated with pulmonary embolism-deep
      venous thrombosis by oligo microarray].
AB  - OBJECTIVE: To find out the gene clusters associated with pulmonary embolism-deep
      venous thrombosis (PE-DVT) and elucidate the molecular genetic mechanism of PE.
      METHODS: Peripheral venous blood samples were collected from 9 PE patients and 33
      normal controls. The total RNA was extracted and purified. Nine PE cRNA probes
      labeled with cyanine 3 were constructed, and one standard cRNA probe labeled with
      cyanine 5 was synthesized based on the total RNA mixture of the controls.
      Hybridization with Agilent Whole Human Genome Oligo Microarray was performed.
      Eleven of the genes screened were randomly selected to be amplified by
      fluorescence quantitative PCR (FQ-PCR). RESULTS: 434 differential expression
      genes were screened from the 9 microarrays, including 36 gene transcripts.
      Associated with blood coagulation, 20 with immune or inflammatory response, 29
      with metabolism, 26 with cell differentiation and apoptosis, 25 with cell
      growth/maintenance, 22 with cell-cell signaling or signal transduction, 14 with
      cytoskeleton or motility, 15 with ion channel or ion transport, 14 with
      transcription, and 6 with DNA/RNA binding. These 11 of these genes were randomly
      selected to be amplified by FQ-PCR. The differential expression of the 11
      selected genes was consistent with the microarray. CONCLUSION: The differential
      expression of a lot of genes in the body may play a role in the process of
      initiation and development of PE-DVT.

PMID- 18036323
TI  - [Detection of urological and male genital tumors diagnosed in Beijing Hospital
      1995 - 2004].
AB  - OBJECTIVE: To investigate the diagnostic condition of urological and male genital
      tumors in Beijing Hospital during the period 1995 - 2004. METHODS: The clinical
      data of 1245 patients diagnosed as with urological and male genital tumors that
      were hospitalized in the Department of Urology, Beijing Hospital from 1 January
      1995 to 31 December 2004, 957 males and 288 females, were analyzed
      retrospectively. RESULTS: The 1245 with urological and male genital tumors
      accounted for 20.96% of the patients hospitalized in the Department of Urology of
      this hospital in the same period. The commonest malignancies included
      transitional cell carcinoma of bladder (n = 387), carcinoma of prostate (n =
      271), and clear cell carcinoma of kidney (n = 250). The detected numbers of cases
      of these three kinds of malignancies increased year by year. The ratio of
      metastatic carcinoma in prostate and kidney decreased with each passing year.
      Before 1999 75.48% of the patients with prostate carcinoma visited the hospital
      because of low urinary tract symptom (LUTS), and only 12.48% because of
      abnormalities discovered during physical examination, However, after 2000 the
      percentage of the prostate carcinoma patients who visited the hospital because of
      LUST deceased to 54.44%, and those because of abnormalities discovered during
      physical examination increased to 40.99% (P < 0.01). CONCLUSION: The improvement
      of diagnostic methods has changed the condition of tumor diagnosis in recent
      years.

PMID- 18036324
TI  - [Inhibition effects of constituents of Radix Salviae Miltiorrhizae on
      proliferation and procollagen transcription of dermal fibroblasts in systemic
      sclerosis].
AB  - OBJECTIVE: To study the effects of tanshinone IIA, danshensu, lithospermate, and
      protocatechualdehyde on proliferation and procollagen mRNA synthesis of dermal
      fibroblasts from patients with systemic sclerosis (SSc). METHODS: Dermal
      fibroblasts were obtained from 5 patients with SSc, 2 males and 3 females, and
      sex and age-matched 5 patients undergoing plastic surgery, cultured, and then co
      cultured with tanshinone IIA, danshensu, lithospermate, and protocatechualdehyde
      respectively. MTT test was used to study the effects of the four constituents on
      fibroblasts cell proliferation. RT-PCR was used to detect the level of
      procollagen mRNA expression in the control fibroblasts and in the SSc fibroblasts
      before and after the addition of the four constituents. RESULTS: The 4
      constituents all suppressed the proliferation of fibroblasts from SSc patients,
      with tanshinone IIA being the most effective. The 4 constituents remarkably
      inhibited the mRNA expression of type I and III procollagen of the fibroblasts
      with tanshinone II A showing the most inhibition effect that reduced the
      expressions of procollagen I mRNA by 47% and procollagen III mRNA by 45%.
      CONCLUSION: Of the four constituents, tanshinone IIA is the most suppressive
      effect on the cell proliferation and type I and type III procollagen synthesis of
      SSc fibroblasts, demonstrating that it has a more antifibrotic effect.

PMID- 18036325
TI  - [Identification of the beta(2)GPI-binding receptor on hepatocyte membrane].
AB  - OBJECTIVE: To identified the beta(2)-glycoprotein I (beta(2)GPI)-bound receptor
      on the membrane of hepatocellular carcinoma cells, and to analyze its function.
      METHODS: Through the beta(2)GPI-affinity chromatography column, the peptide
      polysome-mRNA complex specially binding to beta(2)GPI stayed with the column and
      was separated from the whole polysome of liver cells. Then it was eluted and
      collected. With the cDNA synthesis kit and cDNA PCR kit, the corresponding cDNA
      was obtained and sequenced. RT-PCR was used to amplify annexin II, and flow
      cytometry was used to study the competitive binding of annexin II with beta(2)GPI
      to SMMC-7721 cells. RESULTS: 1.1 kb cDNA fragment of the specific binding protein
      of beta(2)GPI on liver cell membrane was obtained. And the sequence of cDNA
      shared a high homology with human annexin II (98%). Annexin II was expressed on
      the membrane of the hepatocellular carcinoma cells of the line SMMC-7721, and 1
      microl and 4 microl of annexin II caused the binding rate of beta(2)GPI-GFP with
      SMMC-7721 cells from 15.58% to 13.66% and 7.56% respectively. CONCLUSION: The
      receptor of beta(2)GPI on the membrane of hepatocellular carcinoma cells is
      annexin II, and beta(2)GPI may help HBV invade hepatic cells through combing with
      annexin II on the liver cell membrane.

PMID- 18036326
TI  - [Ginkgolides induced ischemic tolerance and its possible molecular mechanism:
      experiment with rat pheochromocytoma cell line PC12].
AB  - OBJECTIVE: To explore the ischemic tolerance induced by Ginkgolides in PC12 cells
      and its possible molecular mechanism. METHODS: An ischemic model was developed in
      PC12 cell line with deprivation of oxygen-glucose (OGD). PC12 cells was randomly
      divided into four groups: 9 hours ischemia group, 1.5 hours ischemic
      preconditioning + 9 hours ischemia group, Ginkgolides preconditioning + 9 hours
      ischemia group and control group. Cells viability was examined by MTT assay and
      cellular morphology was analyzed under the phase-contrast microscope. The
      molecular mechanism of Ginkgolides induced ischemic tolerance was pinpointedby
      analyzing the expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) and
      erythropoietin (EPO). The DNA binding activities of HIF-1 in PC12 cells were
      examined by electrophoretic mobility shift assay. RESULTS: In ischemic model, the
      viability of PC12 cells was decreased (49.3 +/- 2.8)% after OGD for 9 hours.
      However, Ginkgolides pretreatment could remarkably increase the viability of PC12
      cells (65.9 +/- 2.8)% (P < 0.01). Pretreatment of Ginkgolides for 24 hours could
      largely rescue the morphology of PC12 cells to the damage of subsequent exposure
      to 9 hours ischemia insult, many cellular bodies were intact and many neurites
      and network of PC12 cells were still exist. At molecular level, the expression of
      HIF-1alpha was greatly induced by Ginkgolides treatment after compared with the
      control group (P < 0.01). The DNA binding activities of HIF-1 in PC12 cells
      pretreated with Ginkgolides was also increased. And it activates its downstream
      target EPO, the protein expression (P < 0.01). CONCLUSION: The pretreatment of
      Ginkgolides could induce tolerance against ischemia in PC12 cells. The molecular
      mechanism of this process may involve in the activation of HIF-1alpha and the DNA
      binding activity of HIF-1 and its downstream target EPO.

PMID- 18036327
TI  - [Biocompatibility of extracellular matrix of homologous fascia lata as material
      for renal trauma repair].
AB  - OBJECTIVE: To study the biocompatibility of extracellular matrix (ECM) of
      homologous fascia lata, so as to identify whether this material can be used in
      repair of renal trauma. METHODS: The fascia latae of 2 dogs were stripped and
      underwent treatment of decellularizing liquid, DNAse, RNAse, etc. so as to
      produce ECM. Twenty Kunming mice were randomly divided into 2 equal groups to be
      injected with the extractive liquid of the ECM or normal saline. 4, 24, 48, and
      72 hours later the mice were observed so as to examine the toxicity of the ECM.
      Mouse fibroblasts of the line L929 were cultured. ECM was added into the
      suspension of the cells, and 2, 4, and 7 days later the relative growth rate
      (RGR) of the cells was observed by MTT method. The left kidneys of 10 dogs were
      cut by knife so as to establish kidney injury models, and the wounds were covered
      by prepared ECM pieces immediately. 1 and 2 weeks, and 1, 2, and 4 months after
      the operation respectively the dogs were killed and light microscopy and electron
      microscopy were conducted to observe the condition of the wounds. RESULTS: No
      abnormal situation was found in the mice after the extractive liquids of the ECM
      was injected into their bodies at any time point. MTT method showed that no
      obvious cytotoxicity was seen in the L292 cells, the RGR levels 2, 4, and 7 days
      were 112%, 96%, and 97% respectively, and the cytotoxic grade were 0, 1, and 1
      respectively. No obvious infiltration of inflammatory cells into the local site
      of renal repair could be seen, only mild adhesion to the surrounding tissues was
      found at different time-points after operation. CONCLUSION: With good
      biocompatibility, ECM of homologous fascia lata may be used as an ideal tissue
      engineering material for renal repair.

PMID- 18036328
TI  - [Effect of aldosterone on the expression of plasminogen activator inhibitor-1 in
      renal mesangial cells: experiment with rat renal mesangial cells].
AB  - OBJECTIVE: To evaluate the effects of aldosterone (ald) on the expression of
      plasminogen activator inhibitor-1 (PAI-1) in renal mesangial cells (MCs) and the
      changes after aldosterone was blocked with spironolactone. METHODS: Rat MCs of
      the line HBZY-1 were cultured and divided into 5 groups: ald group, treated with
      aldosterone (1 micromol/L or 100 nmol/L), ald combined with spironolactone 1
      nmol/L for 24 hours, and control group. Anotfher cells were cultured and treated
      with ald 100 nmol/L for 0, 0.5, 1, 2, 4, 6, 8, and 24 h respectively or treated
      with ald of the concentrations of 10(-5), 10(-6), 10(-7), 10(-8), 10(-9), 10(
      10), pr 10(-11) mol/L. RT-PCR and Western blotting were used to detect the mRNA
      and protein expression of PAI-1. Confocal laser scanning microscopy was used to
      detect the ROS level in the MCs. The transforming growth factor-beta1 (TGF-beta1)
      level in the medium was detected by ELISA. RESULTS: The PAI-1 mRNA and protein
      levels of the ald 100 nmol/L and 1 micromol/L groups became 2 times and 1.8
      times, and 1.7 times and 1.9 times respectively those of the control group (all P
      < 0.01). The PAI-1 mRNA and protein levels of the ald + spirolactone group were
      not significantly different from those of the control group (all P > 0.05). The
      TGF-beta1 levels of the 100 nmol/L and 1 micromol/L aldosterone groups were 147
      pg/ml +/- 27 pg/ml and 183 pg/ml +/- 25 pg/ml respectively, both significantly
      higher than that of the control group (75 pg/ml +/- 23 pg/ml, both P < 0.01). The
      TGF-beta1 levels of the groups with spirolactone were not significantly different
      from that of the control group (both P > 0.05). The ROS levels of the 1
      micromol/L and 100 nmol/L ald groups were 4.87 times and 4.77 times that of the
      control group (both P < 0.01), and the ROS levels of the groups with spirolactone
      were 1.95 time and 1.66 times that of the control group (both P > 0.05). 100
      nmol/L ald time-dependently increased the PAI-1 level since 4 hours after
      exposure to ald (all P < 0.05). Aldosterone dose-dependently increased the PAI-1
      level (all P < 0.05). CONCLUSION: Aldosterone upregulates the production of PAI-1
      by MCs and increases the expression of TGF-beta1 and cellular ROS in the MCs
      significantly, which is mediated through mineralocorticoid receptor.

PMID- 18036331
TI  - Characterization of active site variants of xanthine hydroxylase from Aspergillus
      nidulans.
AB  - Xanthine/alpha-ketoglutarate (alphaKG) dioxygenase (XanA) is a non-heme
      mononuclear Fe(II) enzyme that decarboxylates alphaKG to succinate and CO(2)
      while hydroxylating xanthine to generate uric acid. In the absence of a XanA
      crystal structure, a homology model was used to target several putative active
      site residues for mutagenesis. Wild-type XanA and ten enzyme variants were
      purified from recombinant Escherichia coli cells and characterized. The H149A and
      D151A variants were inactive and the H340A variant exhibited only 0.17% of the
      wild-type enzyme activity, consistent with the proposed role of His149, Asp151,
      and His340 as Fe ligands. The K122A variant led to a 2-fold increase in the K(d)
      of alphaKG as measured by fluorescence quenching analysis, in agreement with
      Lys122 acting to stabilize the binding of alphaKG. The N358A variant exhibited a
      23-fold decrease in k(cat)/K(m) compared to wild-type XanA, pointing to a key
      role of Asn358 in catalysis. 9-Methylxanthine was exploited as an alternate
      substrate, and the C357A, E137A, and D138A variants were found to exhibit
      relatively enhanced activity consistent with Cys357, Glu137, and Asp138 being
      proximal to N-9 or involved in its proper positioning. 6,8-Dihydroxypurine was
      identified as a slow-binding competitive inhibitor of XanA, and significant
      decreases (E137A and D138A) or increases (Q356A and N358A) in K(i)(app) of the
      variants were interpreted in terms of distinct interactions between this compound
      and the corresponding active site side chains. Further support for Cys357
      residing at the active site was obtained using thiol-specific reagents that
      inactivated wild-type enzyme (with partial protection by substrate), whereas the
      C357A variant was resistant to these reagents. The Q101A, Q356A, and C357A
      variants showed elevated ferroxidase activity in the absence of substrates,
      pointing to the presence of the corresponding side chains at the active site.
      These results confirm most aspects of the homology model and provide additional
      insight into the enzyme reactivity.

PMID- 18036332
TI  - Interacting proteins Rtt109 and Vps75 affect the efficiency of non-homologous end
      joining in Saccharomyces cerevisiae.
AB  - One of the key pathways for DNA double-stranded break (DSB) repair is the non
      homologous end-joining (NHEJ) pathway, which directly re-ligates two broken ends
      of DNA. Using a plasmid repair assay screen, we identified that the deletion
      strain for RTT109 had a reduced efficiency for NHEJ in yeast. This deletion
      strain also had a reduced efficiency to repair induced chromosomal DSBs in vivo.
      Tandem-affinity purification of Rtt109 recovered Vps75 as a physical interacting
      protein. Deletion of VPS75 was also shown to have an effect on the efficiency of
      NHEJ in both the plasmid repair and the chromosomal repair assays. In addition,
      deletion mutants for both RTT109 and VPS75 showed hypersensitivity to different
      DNA damaging agents. Our genetic interaction analysis supports a role for RTT109
      in DNA damage repair. We propose that one function of the Rtt109-Vps75
      interacting protein pair is to affect the efficiency of NHEJ in yeast. Vps75 but
      not Rtt109 also seem to have an effect on the efficiency of DSB repair using
      homologous recombination.

PMID- 18036333
TI  - Synchronized changes in transcript levels of genes activating cold exposure
      induced thermogenesis in brown adipose tissue of experimental animals.
AB  - To identify genes whose expression in brown adipose tissue (BAT) is up- or down
      regulated in cold-exposed rats, we performed microarray analysis of RNA samples
      prepared from the BAT of cold-exposed rats and of rats kept at room temperature.
      Previously reported elevations of transcript levels of uncoupling protein (UCP1),
      type II iodothyronine deiodinase (DIO2), and type III adenylate cyclase (AC3) in
      the BAT of cold-exposed rats over those in that of rats maintained at room
      temperature were confirmed. In addition to these changes, remarkable elevations
      of the transcript levels of several genes that seemed to be associated with the
      processes of cell-cycle regulation and DNA replication were detected in the BAT
      of cold-exposed rats, possibly reflecting the significant proliferation of brown
      adipocytes in response to cold exposure. Up-regulation of the gene encoding
      sarcomeric mitochondrial type creatine kinase in the BAT of cold-exposed rats was
      also detected by microarray analysis, but subsequent Northern analysis revealed
      that the expression of not only the sarcomeric mitochondrial type enzyme, but
      also that of 2 other subtypes, i.e., cytoplasmic brain type and cytoplasmic
      muscle type, was elevated in the BAT of cold-exposed rats. Microarray analysis
      also revealed a significant expression of myoglobin in BAT and its elevation in
      the BAT of cold-exposed rats, and this result was supported by calibrated
      Northern analysis. On the contrary, several genes such as regulator of G-protein
      signaling 2 and IMP dehydrogenase 1 were down-regulated in the BAT of cold
      exposed rats. The physiological meaning of these changes accompanying cold
      exposure was discussed.

PMID- 18036334
TI  - Unfolding of C-phycocyanin followed by loss of non-covalent chromophore-protein
      interactions 1. Equilibrium experiments.
AB  - Optical spectroscopic properties of the covalently linked chromophores of
      biliproteins are profoundly influenced by the state of the protein. This has been
      used to monitor the urea-induced denaturation of C-phycocyanin (CPC) from
      Mastigocladus laminosus and its subunits. Under equilibrium conditions,
      absorption, fluorescence and circular dichroism of the chromophores were
      monitored, as well as the circular dichroism of the polypeptide. Treatment of CPC
      trimers (alphabeta)3 resulted first in monomerization (alphabeta), which was
      followed by a complex unfolding process of the protein. Loss of chromophore
      fluorescence is the next process at increasing urea concentrations; it indicates
      increased flexibility of the chromophore while maintaining the native, extended
      conformation, and a less compact but still native-like packing of the protein in
      the regions sampled by the chromophores. This was followed by relaxation of the
      chromophores from the energetically unfavorable extended to a cyclic-helical
      conformation, as reported by absorption and CD in the visible range, indicating
      local loss of protein structure. Only then is the protein secondary structure
      lost, as reported by the far-UV CD. Sequential processes were also seen in the
      subunits, where again the chromophore-protein interactions were reduced before
      the unfolding of the protein. It is concluded that the bilin chromophores are
      intrinsic probes suitable to differentiate among different processes involved in
      protein denaturation.

PMID- 18036335
TI  - Subunit-selective role of the M3 transmembrane domain of the nicotinic
      acetylcholine receptor in channel gating.
AB  - The nicotinic acetylcholine receptor (AChR) can be either hetero-pentameric,
      composed of alpha and non-alpha subunits, or homo-pentameric, composed of alpha7
      subunits. To explore the subunit-selective contributions of transmembrane domains
      to channel gating we analyzed single-channel activity of chimeric muscle AChRs.
      We exchanged M3 between alpha1 and epsilon or alpha7 subunits. The replacement of
      M3 in alpha1 by epsilonM3 significantly alters activation properties. Channel
      activity appears as bursts of openings whose durations are 20-fold longer than
      those of wild-type AChRs. In contrast, 7-fold briefer openings are observed in
      AChRs containing the reverse epsilon chimeric subunit. The duration of the open
      state decreases with the increase in the number of alpha1M3 segments, indicating
      additive contributions of M3 of all subunits to channel closing. Each alpha1M3
      segment decreases the energy barrier of the closing process by approximately 0.8
      kcal/mol. Partial chimeric subunits show that small stretches of the M3 segment
      contribute additively to the open duration. The replacement of alpha1 sequence by
      alpha7 in M3 leads to 3-fold briefer openings whereas in M1 it leads to 10-fold
      prolonged openings, revealing that the subunit-selective role is unique to each
      transmembrane segment.

PMID- 18036336
TI  - Structure and function of claudins.
AB  - Claudins are tetraspan transmembrane proteins of tight junctions. They determine
      the barrier properties of this type of cell-cell contact existing between the
      plasma membranes of two neighbouring cells, such as occurring in endothelia or
      epithelia. Claudins can completely tighten the paracellular cleft for solutes,
      and they can form paracellular ion pores. It is assumed that the extracellular
      loops specify these claudin functions. It is hypothesised that the larger first
      extracellular loop is critical for determining the paracellular tightness and the
      selective ion permeability. The shorter second extracellular loop may cause
      narrowing of the paracellular cleft and have a holding function between the
      opposing cell membranes. Sequence analysis of claudins has led to differentiation
      into two groups, designated as classic claudins (1-10, 14, 15, 17, 19) and non
      classic claudins (11-13, 16, 18, 20-24), according to their degree of sequence
      similarity. This is also reflected in the derived sequence-structure function
      relationships for extracellular loops 1 and 2. The concepts evolved from these
      findings and first tentative molecular models for homophilic interactions may
      explain the different functional contribution of the two extracellular loops at
      tight junctions.

PMID- 18036337
TI  - Anti-oxidant effect of ascorbic and dehydroascorbic acids in hippocampal slice
      culture.
AB  - Ascorbic acid (AA) and dehydroascorbic acid (DHA) have been shown to have
      protective effects as anti-oxidants in experimental neurological disorder models
      such as stroke, ischemia, and epileptic seizures. The present study was conducted
      to examine the protective effects of AA and DHA on kainic acid (KA) neurotoxicity
      using organotypic hippocampal slice cultures. After 12h KA treatment, significant
      delayed neuronal death was detected in the CA3, but not the CA1, region.
      Pretreatment with intermediate doses of AA and DHA significantly prevented cell
      death and inhibited reactive oxygen species (ROS) level, and mitochondrial
      dysfunction in the CA3 region. In contrast, pretreatment with low or high doses
      of AA or DHA was not effective. These data suggest that pretreatment with both AA
      and DHA has dose-dependent neuroprotective effects on KA-induced neuronal injury
      through inhibiting ROS generation and mitochondrial dysfunction.

PMID- 18036338
TI  - Role of short-chain hydroxyacyl CoA dehydrogenases in SCHAD deficiency.
AB  - Short-chain hydroxyacyl CoA dehydrogenase deficiency is an ill-defined, severe
      pediatric disorder of mitochondrial fatty acid beta-oxidation of short-chain
      hydroxyacyl CoAs. To understand the relative contributions of the two known short
      chain hydroxyacyl CoA dehydrogenases (HADH) tissue biopsies of six distinct
      family individuals were analyzed and kinetic parameters were compared. Steady
      state kinetic constants for HADH 1 and HADH 2 suggest that type 1 is the major
      enzyme involved in mitochondrial beta-oxidation of short-chain hydroxyacyl-CoAs.
      Two patients are heterozygous carriers of a HADH 1 polymorphism, whereas no
      mutation is detected in the HADH 2 gene of all patients. The data suggest that
      protein interactions rather than HADH mutations are responsible for the disease
      phenotype. Pull-down experiments of recombinant HADH 1 and 2 with human
      mitochondrial extracts reveal two proteins interacting with HADH 1, one of which
      was identified as glutamate dehydrogenase. This association provides a possible
      link between fatty acid metabolism and the hyperinsulinism/hyperammonia syndrome.

PMID- 18036339
TI  - Persistent antibody and T cell responses induced by HIV-1 DNA vaccine delivered
      by electroporation.
AB  - Intramuscular needle injection of HIV-1 DNA vaccines typically elicits weak
      immune responses in immunized individuals. To improve such responses, the
      immunogenicity of a vaccine consisting of electroporated DNA followed by
      intramuscular protein boost was evaluated in rabbits and macaques. In macaques,
      electroporation of low dose DNA encoding HIV-1 env followed by gp120 protein
      elicited Th1 cytokines and functional CTL that persisted for over 1 year. In both
      macaques and rabbits, robust anti-envelope antibodies, elicited by electroporated
      DNA, were augmented by gp120 protein and such responses neutralized sensitive
      SHIV isolates. These findings highlight efficient priming of immune responses by
      electroporated DNA that in conjunction with protein boost may give rise to long
      term immunity in immunized hosts.

PMID- 18036340
TI  - Lipid transfer proteins from Rosaceae fruits share consensus epitopes responsible
      for their IgE-binding cross-reactivity.
AB  - Four IgE-binding epitopes have been characterized that cover a large area (40%)
      of the molecular surface of lipid transfer protein allergens of Rosaceae (apple,
      peach, apricot, and plum). They mainly correspond to electropositively charged
      regions protruding on the molecular surface of the modeled apple (Mal d 3),
      apricot (Pru ar 3), and plum (Pru d 3) allergens. Two of these epitopes consist
      of consensus epitopes structurally conserved among the lipid transfer protein
      allergens from the Rosaceae. Their occurrence in different lipid transfer protein
      allergens presumably accounts for the IgE-binding cross-reactivity often observed
      among different Rosaceae fruits. In this respect, LTP consist of phylogenetically
      and structurally-related pan allergens. However, the IgE-binding cross
      reactivity due to fruit lipid transfer protein has varying degrees of clinical
      relevance and this cross-reactivity is not necessarily accompanied by a cross
      allergenicity to the corresponding fruits.

PMID- 18036341
TI  - Changes in cell morphology and cytoskeletal organization are induced by human
      mitotic checkpoint gene, Bub1.
AB  - The mitotic spindle checkpoint prevents the onset of anaphase and subsequent cell
      division until chromosomes are properly aligned on a bipolar spindle. Thus, it
      regulates the cell division cycle by keeping cells with defective spindles from
      leaving mitosis. The budding uninhibited by benzimidazole (Bub1) is a key
      component of mitotic checkpoint. Bub1 encodes a serine/threonine kinase required
      for mitotic spindle checkpoint function. The regulation of cell morphology in
      eukaryotic cells is a complex process involving major components of the
      cytoskeleton including actin microfilaments, microtubules, and intermediate
      filaments (IFs). Here we show that Bub1 directly affects the structural integrity
      of IFs. Constitutive expression of Bub1 caused disappearance of filamentous
      vimentin, a type III IF, and consequently changed cell morphology. Expression of
      kinase domain-deleted Bub1 induced neither morphological change nor disappearance
      of vimentin. These observations suggest that Bub1 not only regulates the cell
      cycle, but also may be involved in the cytoskeletal control in interphase cells.

PMID- 18036342
TI  - The RSV F and G glycoproteins interact to form a complex on the surface of
      infected cells.
AB  - In this study, the interaction between the respiratory syncytial virus (RSV)
      fusion (F) protein, attachment (G) protein, and small hydrophobic (SH) proteins
      was examined. Immunoprecipitation analysis suggested that the F and G proteins
      exist as a protein complex on the surface of RSV-infected cells, and this
      conclusion was supported by ultracentrifugation analysis that demonstrated co
      migration of surface-expressed F and G proteins. Although our analysis provided
      evidence for an interaction between the G and SH proteins, no evidence was
      obtained for a single protein complex involving all three of the virus proteins.
      These data suggest the existence of multiple virus glycoprotein complexes within
      the RSV envelope. Although the stimulus that drives RSV-mediated membrane fusion
      is unknown, the association between the G and F proteins suggest an indirect role
      for the G protein in this process.

PMID- 18036343
TI  - Taurine increases cell proliferation and generates an increase in [Mg2+]i
      accompanied by ERK 1/2 activation in human osteoblast cells.
AB  - Taurine has been reported to influence bone metabolism, and its specific
      transport system, the taurine transporter, is expressed in osteoblasts. The mean
      [Mg2+]i was 0.51+/-0.01 mM in normal culture media. Taurine caused an increase in
      [Mg(2+)]i by 0.72+/-0.04 mM in human osteoblast (HOB) cells. This increment in
      [Mg2+]i was inhibited significantly by PD98059, nifedipine, lidocaine, and
      imipramine. Taurine was also shown to stimulate the activation of ERK 1/2. This
      taurine-stimulated ERK 1/2 activation was inhibited by PD98059. In the present
      study, taurine was shown to increase cell proliferation and generate an increase
      in [Mg2+]i accompanied by ERK 1/2 activation in HOB cells.

PMID- 18036344
TI  - Compound C inhibits hypoxic activation of HIF-1 independent of AMPK.
AB  - The key transcription factor that regulates the cellular responses to hypoxia is
      hypoxia inducible factor-1 (HIF-1). The signaling mechanisms that regulate the
      hypoxic activation of HIF-1 are not fully understood. Our objective here was to
      test whether AMP-activated kinase (AMPK) was an upstream regulator of HIF-1. Our
      results show that AMPK is not required for the hypoxic activation of HIF-1.
      Interestingly, the AMPK inhibitor, Compound C, inhibits the hypoxic activation of
      HIF-1 independent of AMPK. Furthermore, we demonstrate that Compound C functions
      as a repressor of HIF-1 by inhibiting respiration and suppressing mitochondrial
      generated ROS.

PMID- 18036346
TI  - Substitution of isoleucine L177 by histidine in Rhodobacter sphaeroides reaction
      center results in the covalent binding of PA bacteriochlorophyll to the L
      subunit.
AB  - In this work, we report the unique case of bacteriochlorophyll (BChl) - protein
      covalent attachment in a photosynthetic membrane complex caused by a single
      mutation. The isoleucine L177 was substituted by histidine in the photosynthetic
      reaction center (RC) of Rhodobacter sphaeroides. Pigment analysis revealed that
      one BChl molecule was missing in the acetone-methanol extract of the I(L177)H
      RCs. SDS-PAGE demonstrated that this BChl molecule could not be extracted with
      organic solvents apparently because of its stable covalent attachment to the
      mutant RC L-subunit. Our data indicate that the attached bacteriochlorophyll is
      one of the special pair BChls, P(A). The chemical nature of this covalent
      interaction remains to be identified.

PMID- 18036345
TI  - Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression
      via ERK pathway in mouse NIH-3T3 fibroblasts.
AB  - Intact osteoactivin, a novel type I membrane glycoprotein, were shed at a dibasic
      motif in the juxtamembrane region in C2C12 myoblasts. Extracellular fragments
      were secreted into the culture media by a putative metalloprotease. Extracellular
      fragments of osteoactivin, but not control protein, induced matrix
      metalloprotease-3 (MMP-3) expression in NIH-3T3 fibroblasts. Epidermal growth
      factor (ERK) kinase inhibitors inhibited the osteoactivin-mediated MMP-3
      expression, whereas the extracellular fragment of osteoactivin activated ERK1/2
      and p38 in the mitogen-activated protein kinase pathway. Our results suggest that
      the extracellular fragments of osteoactivin produced by shedding act as a growth
      factor to induce MMP-3 expression via the ERK pathway in fibroblasts.

PMID- 18036347
TI  - Mutations of the SM protein Sly1 resulting in bypass of GTPase requirement in
      vesicular transport are confined to a short helical region.
AB  - Ypt/Rab GTPases and Sec1/Munc18 (SM) proteins are key components of the membrane
      fusion machinery. Here, we describe new mutants of the yeast SM protein Sly1 that
      specifically bypass the need for GTPases Ypt1 and Ypt6 in vesicular transport.
      All sequence alterations are confined to a short alpha-helix (alpha-20), which is
      conserved in fungal Sly1 proteins and, when deleted, results in GTPase
      suppression. Whereas Sly1p of the evolutionarily distant fission yeast
      Schizosaccharomyces pombe can functionally replace Sly1p in Sacchromyces
      cerevisiae, mammalian homologues cannot. This indicates that alpha-20 in fungal
      Sly1p plays an important role in mediating Ypt/Rab-regulated Sly1p function in
      membrane fusion.

PMID- 18036348
TI  - Hsp90-mediated inhibition of FKBP38 regulates apoptosis in neuroblastoma cells.
AB  - The FK506-binding protein 38 (FKBP38) is a pro-apoptotic regulator of Bcl-2 in
      neuroblastoma cells. Hsp90 inhibits the pro-apoptotic FKBP38/CaM/Ca(2+) complex
      and thus prevents interactions between FKBP38 and Bcl-2. Here we show that Hsp90
      increases cell survival rates of neuroblastoma cells after apoptosis induction.
      Depletion of FKBP38 by short interference RNA significantly decreased the anti
      apoptotic effect of Hsp90 expression. In addition, the influence of high cellular
      Hsp90 levels was only observed in post-stimulation apoptosis that is sensitive to
      selective FKBP38 active site inhibition. Similar anti-apoptotic effects in
      neuroblastoma cells were observed after stimulation of endogenous Hsp90
      expression. Hence, the inhibition of FKBP38 by Hsp90 participates in programmed
      cell death control of neuroblastoma cells.

PMID- 18036349
TI  - Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways.
AB  - Energy homeostasis in mammals is achieved through tight regulation of tissue
      specific metabolic pathways that become dysregulated in metabolic diseases
      including diabetes and obesity. At the molecular level, main nutrient and
      hormonal signaling pathways impinge on expression of genes encoding for metabolic
      enzymes. Among the major components of this transcriptional circuitry are the PGC
      1 alpha transcriptional complexes. An important regulatory mechanism of this
      complex is through acetylation and SIRT1-mediated lysine de-acetylation under low
      nutrient conditions. Activation of SIRT1 can mimic several metabolic aspects of
      calorie restriction that target selective nutrient utilization and mitochondrial
      oxidative function to regulate energy balance. Thus, understanding the PGC-1
      alpha and SIRT1 pathways might have important implications for comprehending
      metabolic and age-associated diseases.

PMID- 18036350
TI  - Insights on calcium-independent phospholipid membrane damage by Lys49-PLA2 using
      tryptophan scanning mutagenesis of bothropstoxin-I from Bothrops jararacussu.
AB  - Bothropstoxin-I (BthTx-I) is a homodimeric Lys49-PLA2 from the venom of the snake
      Bothrops jararacussu, which lacks hydrolytic activity against phospholipid
      substrates, yet permeabilizes membranes by a Ca2+-independent mechanism. The
      interaction of the BthTx-I with model membranes has been studied by intrinsic
      tryptophan fluorescence emission (ITFE) spectroscopy. Nine separate mutants have
      been created each with a unique tryptophan residue located at a different
      position in the interfacial recognition site (IRS) of the protein. The rapid and
      efficient Ca2+-independent membrane damage against unilamellar liposomes composed
      of DPPC/DMPA in a 9:1 molar ratio was unaffected by these substitutions. Binding
      studies revealed low protein affinity for these liposomes and no changes were
      observed in the ITFE properties. In contrast, the binding of all mutants to
      DPPC/DMPA liposomes in a 1:1 molar ratio was stronger, and was correlated with
      altered ITFE properties. The blue-shifted emission spectra and increased emission
      intensity of mutants at positions 31, 67 and 115-117 in the interface recognition
      surface of the protein suggest these regions are partially inserted into the
      membrane. These results are consistent with a model for the Ca2+-independent
      membrane damaging mechanism that involves a transient interaction of the protein
      with the outer phospholipid leaflet of the target membrane.

PMID- 18036351
TI  - Proline modulates the intracellular redox environment and protects mammalian
      cells against oxidative stress.
AB  - The potential of proline to suppress reactive oxygen species (ROS) and apoptosis
      in mammalian cells was tested by manipulating intracellular proline levels
      exogenously and endogenously by overexpression of proline metabolic enzymes.
      Proline was observed to protect cells against H(2)O(2), tert-butyl hydroperoxide,
      and a carcinogenic oxidative stress inducer but was not effective against
      superoxide generators such as menadione. Oxidative stress protection by proline
      requires the secondary amine of the pyrrolidine ring and involves preservation of
      the glutathione redox environment. Overexpression of proline dehydrogenase
      (PRODH), a mitochondrial flavoenzyme that oxidizes proline, resulted in 6-fold
      lower intracellular proline content and decreased cell survival relative to
      control cells. Cells overexpressing PRODH were rescued by pipecolate, an analog
      that mimics the antioxidant properties of proline, and by tetrahydro-2-furoic
      acid, a specific inhibitor of PRODH. In contrast, overexpression of the proline
      biosynthetic enzymes Delta(1)-pyrroline-5-carboxylate (P5C) synthetase (P5CS) and
      P5C reductase (P5CR) resulted in 2-fold higher proline content, significantly
      lower ROS levels, and increased cell survival relative to control cells. In
      different mammalian cell lines exposed to physiological H(2)O(2) levels,
      increased endogenous P5CS and P5CR expression was observed, indicating that
      upregulation of proline biosynthesis is an oxidative stress response.

PMID- 18036352
TI  - Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, and
      mitochondrial electron transport system mediate heat shock-induced MMP-1 and MMP
      9 expression.
AB  - In addition to ultraviolet radiation, human skin is also exposed to infrared
      radiation (IR) from natural sunlight. IR typically increases the skin
      temperature. This study examined whether or not heat shock-induced ROS stimulates
      MMPs in keratinocyte HaCaT cells. In HaCaT cells, heat shock was found to
      increase the intracellular ROS levels, including hydrogen peroxide and
      superoxide. The heat shock treatment induced MMP-1 and MMP-9, but not MMP-2, at
      the mRNA and protein levels. Moreover, heat shock caused the rapid activation of
      the three distinct MAPKs, ERK, JNK, and p38 kinase. The heat shock-induced
      expression of MMP-1 and MMP-9 was significantly suppressed by a pretreatment with
      the antioxidant NAC or catalase. On the other hand, SOD inhibited heat shock
      induced activity of MMP-9 induction, but not MMP-1. A pretreatment with NAC or
      catalase, but not SOD, attenuated the phosphorylation of ERK, JNK, and p38 kinase
      by heat shock. The potential sites of ROS generation by heat shock along with its
      role in the heat shock-induced expression of MMP-1 and MMP-9 were next analyzed.
      These results indicate that heat shock-induced ROS is promoted via NADPH oxidase,
      xanthine oxidase, and mitochondria. Indeed, the NADPH oxidase and xanthine
      oxidase activities were increased by heat shock. Overall, the ROS produced by
      heat shock may play an important role in the heat shock-induced activation of
      MAPKs, which can induce MMP-1 and-9 expressions.

PMID- 18036353
TI  - Refolding of HLA-B27 heavy chains in the absence of beta2m yields stable high
      molecular weight (HMW) protein forms displaying native-like as well as non-native
      like conformational features: implications for autoimmune disease.
AB  - Refolding of the heavy chain of the Class I HLA molecule, HLA-B27, in the absence
      of beta(2)m, yields soluble high molecular weight (HMW) oligomers reminiscent of
      the oligomeric forms of beta(2)m-free heavy chains (FHCs) of class I HLA antigens
      observed on cell surfaces. Here we examine the structural characteristics of HMW
      B27 in respect of features potentially relevant to autoimmunity, such as: (a)
      retention of native-like structure, since this could facilitate non-canonical
      interactions with T-cell receptors even in the absence of bound beta(2)m and
      peptide, or (b) presence of non-native structure, since this could yield novel
      (non-self) antigenic conformational epitopes that could elicit immune attack. We
      report that HMW B27 is characterized by high secondary structural content,
      structural stability, stability to proteolysis by trypsin, and structural
      features that are both partly native-like, and partly non-native-like, as
      assessed through the binding of conformationally-distinguishing and cross
      reacting scFv antibodies specifically selected against HMW B27. We also present
      cell ELISA data with conformation-specific scFv antibodies that distinguish
      between lymphocytes from individuals who are healthy and B27 positive, and those
      who are B27 positive but suffering from ankylosing spondylitis.

PMID- 18036354
TI  - Atorvastatin inhibits GSK-3beta phosphorylation by cardiac hypertrophic stimuli.
AB  - In this study we examined the effect of the statin atorvastatin on the Akt/GSK
      3beta pathway. Our findings indicate that atorvastatin treatment for 15 days
      inhibited pressure overload-induced cardiac hypertrophy and prevented nuclear
      translocation of GATA4 and c-Jun and AP-1 DNA-binding activity. In addition,
      atorvastatin treatment prevented the increase in the phosphorylation of Akt and
      GSK-3beta caused by cardiac hypertrophy, and this effect correlated with an
      increase in protein levels of phosphatase and tensin homolog on chromosome 10
      (PTEN), which negatively regulates the phosphoinositide-3 kinase/Akt pathway. To
      test whether the inhibitory effect of atorvastatin on Akt and GSK-3beta
      phosphorylation was direct we performed in vitro studies using embryonic rat
      heart-derived H9c2 cells, human AC16 cardiomyoblasts and neonatal rat
      cardiomyocytes. Preincubation of cells with atorvastatin prevented Akt/GSK-3beta
      phosphorylation by different hypertrophic stimuli without affecting PTEN protein
      levels. However, atorvastatin prevented endogenous reactive oxygen species (ROS)
      generation and PTEN oxidation, a process that correlates with its inactivation,
      suggesting that atorvastatin prevents ROS-induced PTEN inactivation in acute
      treatments. These findings point to a new potential anti-hypertrophic effect of
      statins, which can prevent activation of the Akt/GSK-3beta hypertrophic pathway
      by modulating PTEN activation by different mechanisms in chronic and acute
      treatments.

PMID- 18036355
TI  - Usefulness of multislice computed tomographic coronary angiography to identify
      patients with abnormal myocardial perfusion stress in whom diagnostic
      catheterization may be safely avoided.
AB  - Computed tomographic angiography (CTA) has been validated for noninvasive
      assessment of coronary anatomy. The aim was to establish whether CTA could guide
      the use of invasive coronary angiography (ICA) in symptomatic patients with
      intermediate risk after myocardial perfusion stress imaging (MPSI). From April
      2005 to February 2006, patients referred for CTA to a cardiology practice were
      entered into a database. Inclusion required symptoms suggestive of coronary
      artery disease and intermediate-risk MPSI. Subjects with intermediate risk after
      MPSI underwent CTA, and if severe stenosis or moderate stenosis matching a
      perfusion defect was found, ICA was performed. If appropriate, patients were then
      sent for revascularization. Clinical follow-up was completed until December 2006.
      Main outcome measures were number of patients sent for ICA, immediate
      revascularization after ICA, and adverse outcomes (death, myocardial infarction,
      and late revascularization). Four hundred twenty-one patients were included.
      Adequate diagnostic-quality images were obtained in 99%. After MPSI-CTA
      assessment, 78 patients (18.5%) were sent for ICA and 343 (81.5%) were medically
      managed. Follow-up was 15+/-3 months. In the group referred for ICA, there were
      50 cases of immediate revascularization, 1 non-ST-segment elevation myocardial
      infarction, 1 death, and 5 patients requiring repeat ICA, 3 of whom underwent
      late revascularization. In the medically managed group, 6 patients required late
      ICA, 1 of whom underwent revascularization. In conclusion, in symptomatic
      patients with suspected coronary artery disease and intermediate-risk MPSI
      results, CTA can identify up to 80% of patients at low risk of events in whom ICA
      may be safely avoided. Additional studies assessing new technologies combining
      MPSI-CTA are needed to refine imaging strategies in these patients.

PMID- 18036356
TI  - Prognostic significance of systolic blood pressure increases in men during
      exercise stress testing.
AB  - Our aim was to investigate whether exercise-induced increase in systolic blood
      pressure (BP) measured during exercise stress testing (EST) adds prognostic
      information to cardiovascular (CV) mortality. EST is ideally suited to evaluate
      the prognostic power of systolic BP; it not only measures systolic BP response to
      exercise but also provides information about exercise capacity and other EST
      variables, which may affect the peak systolic BP. The study population consisted
      of 6,145 consecutive patients who underwent symptom-limited EST. Using the median
      value of change in systolic BP from baseline, patients were grouped according to
      exercise-induced increases in systolic BP<or=43 mm Hg (group A, n=3,062) and
      >or=44 mm Hg (group B, n=3,083). Multivariate analysis was used to adjust for
      baseline differences between the 2 groups with CV mortality as the end point for
      follow-up. Six thousand one hundred forty-five men underwent EST with a mean
      follow-up of 6.6 years. During follow-up, 676 patients died of CV causes with an
      average annual CV mortality of 1.6%. CV mortality was significantly higher in
      group A than in group B (13.7% vs 8.2%, p<0.001). After adjusting for baseline
      differences in the 2 groups using multivariate analysis, an increase in systolic
      BP of <or=44 mm Hg was a significant predictor of mortality (hazard ratio 1.2,
      95% confidence interval 1.02 to 1.44, p<0.05). In conclusion, systolic BP
      response to maximal EST adds prognostic information to CV mortality independent
      of age, ST-segment abnormalities, and exercise capacity. In our study an
      increment in systolic BP of >or=44 mm Hg during EST was associated with a 23%
      improvement in survival over a mean follow-up of >6 years.

PMID- 18036357
TI  - Effect of modified glucose-insulin-potassium on free fatty acids, matrix
      metalloproteinase, and myoglobin in ST-elevation myocardial infarction.
AB  - Insulin has a free fatty acid (FFA)-suppressive effect, vascular endothelial
      growth factor (VEGF)- and matrix metalloproteinase (MMP)-lowering effect, and a
      potential myocardial-protective effect. Whether low-dose insulin exerts these
      effects in patients with acute myocardial infarction (MI) was investigated.
      Thirty-two patients administered thrombolytics and heparin were randomly assigned
      to a modified glucose-insulin-potassium (GIK) regimen (insulin 2.5 U/hour,
      dextrose and potassium titrated to prevent hyperglycemia) or normal saline
      solution and potassium (controls) for 48 hours. Plasma FFA, serum VEGF, pro-MMP
      1, and myoglobin were measured at baseline and sequentially for 48 hours. FFA
      concentrations were increased at baseline; increased further in the first 4 hours
      in controls (p<or=0.008), but not in the GIK group, and were higher at 4 hours in
      controls compared with the GIK group (p=0.0009). VEGF decreased to 7% of baseline
      at 2 hours and remained suppressed in both groups (p=0.0008). Pro-MMP-1 decreased
      in both groups (p<0.005), but this decrease was seen earlier at 2 hours in the
      GIK group compared with 4 hours in controls. There was no significant increase in
      myoglobin at 2 hours in the GIK group, whereas there was a significant increase
      in controls. Mean blood glucose was 131 mg/dl in controls and 124 mg/dl in the
      GIK group (p=NS). In conclusion, this modified GIK regimen attenuated the
      increase in FFA, but did not suppress it to less than the threshold for
      myocardial FFA uptake. It suppressed pro-MMP-1 rapidly and decreased myoglobin,
      whereas heparin suppressed VEGF in patients with acute MI. This provided
      additional rationale for conducting a trial to assess the clinical benefits of
      this modified GIK regimen in patients with acute MI.

PMID- 18036358
TI  - Long-term follow-up of drug-eluting stents when inserted for on- and off-label
      indications.
AB  - This study reports long-term follow-up of the on- and off-label implantation of
      drug-eluting stents (DESs) in a retrospective study of 1,044 patients. Off-label
      implantation of DESs was performed for left main coronary artery lesions,
      bifurcation lesions, bare metal stent restenosis, ostial disease, chronic total
      occlusions, saphenous vein graft lesions, internal mammary artery graft lesions,
      left ventricular ejection fraction <30%, and acute myocardial infarction. End
      points examined were procedural complications, in-hospital myocardial infarction,
      and acute stent thrombosis; end points examined at follow-up were subacute stent
      thrombosis, late stent thrombosis, target vessel revascularization, myocardial
      infarction, death, and major adverse clinical events (MACEs; a composite of
      death, myocardial infarction, and target vessel revascularization). The study
      included 364 patients who received a DES on an on-label basis and 680 patients
      who received a DES on an off-label basis. Patient characteristics were not
      significantly different between the 2 groups, and there was no difference in
      procedural complications or acute stent thrombosis (on-label, 0%; off-label,
      0.3%; p=0.55). There were no significant differences in subacute stent thrombosis
      (0% vs 0.6%, p=0.3), late stent thrombosis (1.4% vs 1.2%, p=0.78), death at
      follow-up (4.9% vs 4.1%, p=0.53), or myocardial infarction (1.9% vs 2.4%,
      p=0.83). Off-label DES implantation was associated with higher rates of target
      vessel revascularization (13.2% vs 24.1%, p=0.0001) and MACEs (17.6% vs 28.2%,
      p=0.0001). Multivariate analysis showed associations between target vessel
      revascularization and MACEs (respective p values) with bare metal stent
      restenosis (p=0.001 and p=0.001), diabetes mellitus (p=0.002 and p=0.001), and
      previous coronary artery bypass grafting (p=0.04 and p=0.01), but not off-label
      DES implantation (p=1.36 and p=1.16). In conclusion, DES use in the off-label
      situations studied was safe and was not associated with increased stent
      thrombosis, myocardial infarction, or death. Multivariate analysis showed that
      off-label DES implantation was not a risk factor for target vessel
      revascularization or MACEs.

PMID- 18036360
TI  - Temporal trends of outcomes for nonagenarians undergoing coronary artery bypass
      grafting, 1993 to 1999.
AB  - Temporal trends in length of stay, discharge disposition, and long-term mortality
      outcomes were examined in nonagenarians who underwent coronary artery bypass
      grafting (CABG) from 1993 to 1999. A total of 4,224 fee-for-service Medicare
      beneficiaries (2,068 women, 2,156 men) aged>or=90 years underwent CABG from 1993
      to 1999. The number of procedures increased from 325 in 1993 to 883 in 1999 among
      all fee-for-service Medicare patients aged>or=65 years. Approximately half of
      CABG procedures were performed on women each year. The mean length of stay
      decreased from 18.0+/-10.8 to 13.3+/-8.8 days from 1993 to 1999 but remained
      longer for women (p<0.001). A greater percentage of women than men were
      discharged to skilled nursing facilities. The overall crude mortality rates
      remained relatively stable at 13.5% at 30 days and 59.0% at 5 years. Men and
      women had comparable short-term mortality outcomes, but men had higher mortality
      rates for 2- to 5-year outcomes. In conclusion, the number of CABG procedures in
      nonagenarians is increasing, with a substantial portion attaining survivorship
      that is equivalent to projected life expectancy.

PMID- 18036359
TI  - Comparison of effects of telmisartan and valsartan on late lumen loss and
      inflammatory markers after sirolimus-eluting stent implantation in hypertensive
      patients.
AB  - We compared the effects of telmisartan and valsartan on late lumen loss and
      inflammatory markers after sirolimus-eluting stent implantation in hypertensive
      patients. This was a prospective, randomized, single-blinded, 8-month follow-up
      study that included hypertensive patients with significant coronary artery
      stenosis treated with telmisartan (n=79) or valsartan (n=80). Risk factors such
      as diabetes, hyperlipidemia, smoking, and obesity were similar between groups.
      After 8 months of follow-up, only the telmisartan group showed significant
      decreases in interleukin-6 and tumor necrosis factor-alpha. The decreases from
      baseline level in total cholesterol and low-density lipoprotein cholesterol
      concentrations were significantly greater in the telmisartan group. The increase
      in adiponectin concentrations from baseline measurements was significantly
      greater in the telmisartan group than in the valsartan group (1.9+/-2.7 vs 0.4+/
      2.0 microg/ml, respectively, p<0.05). Moreover, late lumen loss was significantly
      lower in the telmisartan group than in the valsartan group (0.1+/-0.4 vs 0.3+/
      0.5 mm, respectively, p=0.001). Major adverse cardiac events were similar between
      groups. In conclusion, compared with valsartan, telmisartan was associated with a
      significant decrease in late lumen loss and inflammatory markers after sirolimus
      eluting stent implantation in hypertensive patients with significant coronary
      narrowing.

PMID- 18036361
TI  - The editor's roundtable: chronic stable angina pectoris.

PMID- 18036362
TI  - Meta-analysis of effect of statin treatment on risk of sudden death.
AB  - Despite significant progress in the prevention and treatment of cardiovascular
      disease, sudden cardiac death (SCD) is a major public health problem. Statins
      showed consistent benefits on cardiovascular events, but scant data were
      available about their effects on SCD. This meta-analysis aimed to assess the
      effect of statins on SCD. Additional analyses were carried out to evaluate lipid
      reduction as a possible mediator of the effect. Randomized controlled trials from
      January 1966 to July 2006 were retrieved by searching the MEDLINE database.
      Inclusion criteria were outcome focusing on the incidence of SCD, statin
      treatment compared with placebo or no treatment, randomized design, >or=100
      patients enrolled, and follow-up>or=6 months. Data were independently abstracted
      by 2 investigators using a standardized protocol. Ten randomized controlled
      trials enrolling a total of 22,275 patients were included in the meta-analysis.
      Risks of SCD were 3% in patients receiving statins and 3.8% in control patients.
      Statin treatment was associated with a significant 19% risk reduction for SCD
      (odds ratio 0.81, 95% confidence interval 0.71 to 0.93, p=0.003). In subgroup
      analysis, the benefit of statins was independent from the main characteristics of
      the studies and changes in patient lipid levels during the study. In conclusion,
      our results suggest that statins decrease the risk of SCD.

PMID- 18036363
TI  - Comparison of percent of United States adults weighing>or=300 pounds (136
      kilograms) in three time periods and comparison of five atherosclerotic risk
      factors for those weighing>or=300 pounds to those<300 pounds.
AB  - The radiologic tables used for many imaging procedures have maximum weight
      limits. Many United States (US) adults may have a body weight that exceeds these
      limits and may be ineligible for diagnostic imaging procedures. Using data from
      the National Health and Nutrition Examination Surveys in 1976 to 1980, 1988 to
      1994, and 1999 to 2004, we determined the increase in the percentage and number
      of US adults weighing>or=300 pounds (i.e., the weight limit for an electron beam
      computed tomography table). In addition, the prevalence and clustering of 5
      cardiovascular disease risk factors (current smoking, hypertension, diabetes
      mellitus, low high-density lipoprotein cholesterol, and elevated C-reactive
      protein) was determined for US adults weighing>or=300 pounds, and compared with
      their counterparts weighing<300 pounds. The percentage of US adults, >or=20
      years, weighing>or=300 pounds was 0.10%, 0.79%, and 1.50% in 1976 to 1980, 1988
      to 1994, and 1999 to 2004, respectively (p trend<0.001). This corresponds to an
      increase from 130,000 US adults weighing>or=300 pounds in 1976 to 1980, to
      1,390,000 in 1988 to 1994 and 3,020,000 in 1999 to 2004 (p trend<0.001). After
      age standardization, in 1999 to 2004, 34.1% and 24.0% of adults weighing>or=300
      pounds had 2 and >or=3, respectively, of the 5 cardiovascular disease risk
      factors, compared with 17.7% and 5.3%, respectively, of adults weighing<300
      pounds (each p<0.001). In conclusion, morbid obesity has increased dramatically
      among US adults. The clustering of cardiovascular disease risk factors associated
      with morbid obesity and the exclusion from diagnostic imaging may affect those
      most in need of such procedures.

PMID- 18036364
TI  - Comparison of usefulness of body mass index versus metabolic risk factors in
      predicting 10-year risk of cardiovascular events in women.
AB  - The objective of this study was to prospectively examine the comparative
      importance of body mass index (BMI) and metabolic syndrome (MS) related risk
      factors in predicting future risk of cardiovascular disease (CVD) in women. Of
      25,626 women aged>or=45 years and free of CVD, cancer, and diabetes at baseline
      in the Women's Health Study, all women were classified into 6 groups according to
      3 BMI categories (<25, 25 to 29.9, and >or=30 kg/m2) and the presence or absence
      of MS, defined using modified criteria of the National Cholesterol Education
      Program Adult Treatment Program III. During a median 10-year follow-up, 724
      incident CVD events were documented. Compared with lean women without MS,
      multivariate relative risks of CVD, adjusting for age, physical activity, and
      other covariates, were 2.40 (95% confidence interval [CI] 1.71 to 3.37) for lean
      women who had MS, 1.08 (95% CI 0.87 to 1.33) for overweight women who had no MS,
      3.01 (95% CI 2.30 to 3.94) for overweight women with MS, 1.58 (95% CI 1.21 to
      2.08) for obese women without MS, and 2.89 (95% CI 2.19 to 3.80) for obese women
      with MS. Similar associations were evident for total coronary heart disease, but
      were not significant for total stroke. Overall, although C-reactive protein added
      additional prognostic information beyond BMI and MS, it did not fully account for
      the observed high risk of CVD associated with MS. In conclusion, MS may largely
      account for the increased risk of CVD associated with BMI in apparently healthy
      women.

PMID- 18036365
TI  - Baseline characteristics of participants in the JUPITER trial, a randomized
      placebo-controlled primary prevention trial of statin therapy among individuals
      with low low-density lipoprotein cholesterol and elevated high-sensitivity C
      reactive protein.
AB  - The Justification for the Use of statins in Primary prevention: an Intervention
      Trial Evaluating Rosuvastatin (JUPITER) is a randomized, double-blind, placebo
      controlled primary prevention trial of statin therapy among persons with average
      to low levels of low-density lipoprotein (LDL) cholesterol who are at increased
      cardiovascular risk due to elevated plasma concentrations of the inflammatory
      biomarker high-sensitivity C-reactive protein (hs-CRP). A total of 17,802 persons
      with LDL cholesterol<130 mg/dl (3.36 mmol/L) and hs-CRP>or=2 mg/L were recruited
      from 26 countries and randomly allocated to 20 mg/day rosuvastatin or placebo. In
      contrast to previous studies of statin therapy in primary prevention, JUPITER is
      evaluating a group with modest plasma concentrations of LDL cholesterol (median
      108 mg/dl, interquartile range 94 to 119). Further, the trial includes 6,801
      women (38.2%) and 5,577 participants with metabolic syndrome (32.1%). Thus, in
      addition to broadening our understanding of statin therapy and inflammation, the
      JUPITER trial will provide important and clinically relevant information on
      primary prevention among patients who do not currently qualify for lipid-lowering
      therapy. In conclusion, as 20 mg of rosuvastatin can reduce LDL cholesterol by up
      to 50%, JUPITER will also provide crucial safety data for several thousand
      patients who should achieve LDL cholesterol levels<50 mg/dl on a long-term basis.

PMID- 18036366
TI  - Usefulness of QRS duration to predict response to cardiac resynchronization
      therapy in patients with end-stage heart failure.
AB  - Despite current selection criteria, 20% to 30% of patients treated with cardiac
      resynchronization therapy (CRT) do not benefit. It has been suggested that QRS
      duration may not be the optimal criterion to select patients for CRT. The
      objective of this study was to systematically evaluate the predictive value of
      QRS duration for response to CRT in a large group of consecutive patients. A
      total of 242 patients with heart failure scheduled for implantation of a CRT
      device were studied. Selection criteria for CRT included moderate to severe heart
      failure (New York Heart Association classes III to IV), left ventricular ejection
      fraction (LVEF)<or=35%, and QRS duration>120 ms. Before CRT implantation, QRS
      duration and clinical status were assessed, and 2-dimensional echocardiography
      (LV volumes and LVEF) was performed. Clinical status and changes in LVEF and LV
      volumes were reassessed at 6-month follow-up. After 6 months of CRT, 68% of
      patients were classified as clinical responders (improvement of >or=1 grade in
      New York Heart Association class) and 60% as echocardiographic responders
      (decrease>10% in LV end-systolic volume). At baseline, no significant differences
      were observed in QRS duration between clinical responders and nonresponders and
      between echocardiographic responders and nonresponders. No significant relation
      was demonstrated between baseline QRS duration and improvement in clinical and
      echocardiographic variables at 6-month follow-up. In conclusion, baseline QRS
      duration is not predictive for clinical and echocardiographic responses to CRT at
      6-month follow-up. Better predictors for CRT response are needed.

PMID- 18036367
TI  - Relation of optimal lead positioning as defined by three-dimensional
      echocardiography to long-term benefit of cardiac resynchronization.
AB  - We sought to define the impact of echocardiographically defined left ventricular
      (LV) lead position on the efficacy of cardiac resynchronization therapy (CRT) in
      a serial study using 3-dimensional echocardiography. Fifty-eight consecutive
      patients (53+/-9 years of age; 37 men) with heart failure were included in the
      study. Echocardiograms were obtained before CRT, within 7 days after
      implantation, and at 12+/-2 months of follow-up using a 3-dimensional digital
      ultrasound scanner (iE33, Philips, Andover, Massachusetts). Analysis of the
      temporal course of contraction in 16 LV segments was performed offline using a
      semiautomatic contour tracing software (LV Analysis, TomTec, Unterschleissheim,
      Germany). Based on the resulting volume/time curves the segment with the latest
      minimum of systolic volume in each patient was identified preoperatively (segment
      A). In addition, the temporal difference between the pre- and postoperative
      (within 7 days) minimum of systolic volume was determined for each segment. The
      segment with the longest temporal difference was defined to show the greatest
      effect of CRT. Location of the LV lead tip was assumed to be within this segment
      (segment B). LV lead position was defined as optimal when segments A and B were
      equal and as nonoptimal when they were far from each other. Using this
      definition, 26 patients had a nonoptimal and 32 patients an optimal LV lead
      position. Before CRT ejection fraction (32+/-4% vs 31+/-6%), LV end-systolic and
      end-diastolic volumes (242+/-92 vs 246+/-88 ml, 315+/-82 vs 323+/-90 ml), and
      peak oxygen consumption (14.3+/-1.4 vs 14.6+/-1.5 ml/min/kg) were equal in the 2
      groups. At 12+/-2 months of follow-up, patients with an assumed optimal LV lead
      position showed greater increases of ejection fraction (10+/-2% vs 6+/-3%) and
      peak oxygen consumption (2.4+/-0.3 vs 1.5+/-0.4 ml/min/kg) and greater decreases
      of LV end-systolic (32+/-7 vs 21+/-5 ml) and end-diastolic (20+/-7 vs 13+/-6 ml)
      volumes. In conclusion, correspondence of the segment with the latest
      preoperative LV contraction with the segment with the greatest effect based on
      CRT results in a significantly greater benefit of ejection fraction and peak
      oxygen consumption and a greater improvement in LV remodeling. Thus, there is an
      optimal LV lead position that should be obtained.

PMID- 18036368
TI  - Ventricular long-axis contraction as an earlier predictor of outcome in
      asymptomatic aortic regurgitation.
AB  - The long-term prognostic significance of left ventricular (LV) long-axis
      contraction was investigated prospectively in 65 consecutive patients aged 58+/
      15 years with asymptomatic aortic regurgitation, normal LV ejection fraction at
      rest, and no coronary artery or aortic root disease. A complete transthoracic
      echocardiographic study was performed at baseline and 12 months later. In 24 of
      65 patients with peak systolic wave velocity at the lateral mitral annulus
      (LatS)<9 cm/s, LV diameter (p<0.01), volume (p<or=0.01), mass (p<0.001), and end
      systolic wall stress (p<0.001) significantly increased after 12 months, whereas
      LV shortening and ejection fraction (p=0.001) and tissue Doppler right
      ventricular peak systolic wave velocity (p<0.05) decreased significantly. In
      patients with peak systolic wave velocity at the lateral mitral annulus>or=9
      cm/s, none of these parameters was significantly affected during follow-up.
      Aortic valve replacement was performed in 6 of 24 patients (25%) with peak
      systolic wave velocity at the lateral mitral annulus<9 cm/s and none with peak
      systolic wave velocity at the lateral mitral annulus>or=9 cm/s. In patients with
      peak systolic wave velocity at the lateral mitral annulus<9 cm/s, a cut-off value
      of 6.25 cm/s predicted aortic valve replacement within the next year with 97%
      sensitivity and 83% specificity. In conclusion, ventricular long-axis contraction
      seems to be a reliable indicator for outcome prediction in patients with
      asymptomatic aortic regurgitation.

PMID- 18036369
TI  - Valve structure and survival in quadragenarians having aortic valve replacement
      for aortic stenosis (+/-aortic regurgitation) with versus without coronary artery
      bypass grafting at a single US medical center (1993 to 2005).
AB  - The purpose of this study was to determine the effect of simultaneous coronary
      artery bypass grafting (CABG) and the influence of valve structure on both early
      and late survival in quadragenarians having aortic valve replacement (AVR) for
      aortic stenosis (AS) (with or without aortic regurgitation). We analyzed survival
      and valve structure in 48 adults (12 women), aged 40 to 49 years, having AVR for
      AS from 1993 through 2005 at Baylor University Medical Center, including 7 (15%)
      with and 41 (85%) without simultaneous CABG. Of the 48 quadragenarians, none died
      within 60 days of operation. Assessment of the relation between long-term
      survival and gender, aortic valve structure, preoperative severity of the AS, and
      concomitant CABG was not possible due to the low mortality. Four patients (9%)
      died >60 days after AVR: at 1.8, 6.3, 7.1, and 9.9 years, respectively. The
      aortic valve was congenitally unicuspid in 15 patients (31%), congenitally
      bicuspid in 32 (67%), and 3-cuspid in 1 (2%). In conclusion, of the 48
      quadragenarians having AVR for AS, 47 (98%) had a congenitally malformed aortic
      valve, 60-day mortality was zero, and late mortality was low (8%).

PMID- 18036370
TI  - Frequency and mechanism of persistent systolic anterior motion and mitral
      regurgitation after septal ablation in obstructive hypertrophic cardiomyopathy.
AB  - Relief of obstruction using ventricular septal ablation (VSA) may not eliminate
      systolic anterior motion (SAM) of the mitral valve and mitral regurgitation (MR)
      in patients with obstructive hypertrophic cardiomyopathy. The hypothesis was that
      persistent SAM after VSA was secondary to anterior papillary muscle displacement
      and malcoaptation of mitral valve leaflets and that these findings could predict
      persistence of SAM. Echocardiograms were examined from 37 patients with
      obstructive hypertrophic cardiomyopathy before and 12+/-3 months after VSA.
      Anterior leaflet malposition (anterior-to-posterior leaflet coaptation position
      ratio), papillary muscle malposition (septal-to-lateral/left ventricular internal
      diameter ratio), and anterior position of coaptation relative to the septum
      (coaptation-to-septal distance) were assessed. MR proximal jet width was also
      measured. Of 37 patients, 30 underwent successful VSA (left ventricular outflow
      tract gradient reduction>50%); 22 of 30 and 7 of 7 with <50% reduction (total 29
      of 37; 78%) showed persistent SAM at 12+/-3 months. These patients had more
      anterior malposition of the mitral valve and less MR reduction than those without
      SAM: anterior-to-posterior leaflet coaptation position ratio 0.42+/-0.06 versus
      0.56+/-0.09, septal-to-lateral/left ventricular internal diameter ratio 0.39+/
      0.12 versus 0.55+/-0.12, coaptation-to-septal distance 1.8+/-0.42 versus 2.8+/
      0.30 cm, and MR reduction by 29+/-22% versus 71+/-12% (p<0.0001). Gradients, both
      at rest and provokable, were higher (27+/-33 vs 4+/-5 mm Hg, p=0.0004; >45 mm Hg
      in 9 vs 0, p=0.03, respectively) in patients with persistent SAM. Anterior
      malposition was present before VSA, with anterior-to-posterior leaflet coaptation
      position ratio<0.5 predicting SAM after VSA (p<0.0001). In conclusion, SAM and MR
      were often not eliminated using VSA. Mitral valve malposition was a strong
      predictor of SAM and MR reduction after VSA and may need to be considered in
      optimizing results of this procedure.

PMID- 18036371
TI  - Coronary artery diameters in infants and children with congenital heart disease
      as determined by computed tomography.
AB  - This study was conducted to establish reference curves and formulas for the
      diameters of the coronary arteries in infants and children using computed
      tomography. A total of 145 children (57 female, 88 male) ranging in age from 2
      days to 19 years, 11 months (mean 5 years, 10 months), were retrospectively
      identified, and the diameters of their coronary arteries were quantified. The
      measurability of the coronary arteries, coronary arterial size differences
      between the genders, and relations of the diameters of the coronary arteries to
      age, height, weight, body surface area, and the diameter of the descending aorta
      were examined. Independent-samples Student's t tests, 2-tailed Pearson's
      correlations, and linear regression were used in statistical analysis. The
      measurability of all coronary arteries was 73.3%. No difference in coronary
      arterial size was found between the genders. The diameter of the descending aorta
      correlated most strongly with coronary arterial size. In conclusion, predictive
      formulas and reference curves for coronary arterial diameters in infants and
      children were obtained.

PMID- 18036372
TI  - Impact of body mass index on early outcome and late survival in patients
      undergoing coronary artery bypass grafting or valve surgery or both.
AB  - The influence of body mass on outcome after cardiac surgery remains
      controversial. The aim of this study was to analyze the impact of body mass index
      (BMI) on early and late outcomes in a large series of patients who underwent
      cardiac surgery. We retrospectively analyzed 5,950 consecutive patients who
      underwent cardiac surgery between January 1998 and September 2006. Patients were
      divided into 4 groups defined by BMI (weight divided by square of height
      [kilograms divided by meters squared]): underweight (<or=20 kg/m2): 6%, n=328;
      normal (>20 to <or=25 kg/m2): 34%, n=2,041; overweight (>25 to <or=30 kg/m2):
      38%, n=2,289; obese (>30 kg/m2): 22%, n=1,292. Analysis was further refined by
      performing subgroup analysis according to the surgical procedure (valve surgery,
      coronary artery bypass grafting, and combined valve/coronary artery bypass
      grafting). Main outcome measure was the association between BMI and hospital
      mortality, postoperative morbidities, and late survival. Hospital mortality was
      3.4% (n=203). There was no association between BMI and hospital mortality in the
      entire patient population. Multivariate analysis revealed obesity as an
      independent predictor of hospital mortality in patients who underwent valve
      surgery (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.2 to 4.5, p=0.018).
      Obesity was associated with an increased risk for sternal infection (OR 1.8, 95%
      CI 1.1 to 2.9, p=0.013), whereas underweight correlated with postoperative
      bleeding (OR 2.0, 95% CI 1.1 to 3.6, p=0.017). Underweight was an independent
      predictor for decreased long-term survival (OR 1.8, 95% CI 1.3 to 2.5, p<0.001).
      In conclusion, cardiac surgery can be performed safely in both underweight and
      obese patients but carries a higher postoperative rate of major complications.

PMID- 18036373
TI  - Evolution in the process of screening United States high school student-athletes
      for cardiovascular disease.
AB  - The completeness and potential effectiveness of preparticipation screening for
      high school student athletes in the United States was critiqued in 1997 and
      judged largely inadequate for raising the suspicion of potentially lethal
      cardiovascular diseases. Eight years later, the 2005 history and physical
      examination questionnaires approved in the states as guides to examiners were
      compared with those available in 1997 to determine whether changes had taken
      place in the preparticipation cardiovascular screening process for United States
      high school athletes. The 1997 and 2005 screening questionnaires were analyzed
      with respect to the 12 items recommended by the American Heart Association (AHA).
      The approved screening examiners in each state were also systematically analyzed.
      In 1997, 43 states had approved questionnaire forms, including 12 (28%) with zero
      or only 1 to 4 AHA items and 17 (40%) with >or=9 items. In 2005, 48 states had
      approved forms, but only 1 (2%) had <or=4 AHA items, and 39 (81%) had >or=9 items
      (p=0.005). Between 1997 and 2005, the mean cumulative number of items on all
      forms increased from 6.8+/-4 to 9.7+/-2, a 43% improvement (p<0.01). Although 21
      states showed no or little change (addition of 0 to 2 AHA items), 20 (42%) showed
      substantial increases of >or=5 items. Over the 8-year period, the number of
      states approving nonphysician examiners, including nurse practitioners (21 to 37)
      physician assistants (21 to 35), and naturopathic clinicians or chiropractors (11
      to 18), increased by 64% (p<0.01). In conclusion, the completeness of state
      approved history and physical examination preparticipation screening
      questionnaires for high school students engaged in organized competitive sports
      improved markedly over the period from 1997 to 2005. Paradoxically, however,
      legislation in several states has increased the number of nonphysicians
      performing screening examinations (including chiropractors and naturopathic
      clinicians).

PMID- 18036374
TI  - A review on novel developments and applications of immunosensors in food
      analysis.
AB  - The present review deals with novel developments in immunosensors destined for
      final application in food analysis. In this perspective particular emphasis will
      be given to the most important approaches which recently have been used for
      immunosensor construction and assembling. For this reason, electrochemical,
      surface plasmon resonance (SPR) and quartz crystal microbalance (QCM) techniques
      will be explored in detail and recent and practical examples on food matrices
      will be reviewed. Objective of this survey is to give a general overview of the
      possible application of immunosensors to the food analysis field.

PMID- 18036375
TI  - Microwave assisted volatilization of silicon as fluoride for the trace impurity
      determination in silicon nitride by dynamic reaction cell inductively coupled
      plasma-mass spectrometry.
AB  - A low pressure microwave assisted vapor phase dissolution procedure for silicon
      nitride and volatilization of in situ generated SiF4 has been developed using
      H2SO4, HF and HNO3 for the determination of trace impurities present in silicon
      nitride. Sample was taken in minimum amount (0.5 mL for 100 mg) of H2SO4 and
      treated with vapors generated from HF and HNO3 mixture in presence of microwaves
      in a closed container. An 80 psi pressure with ramp and hold times of 30 min and
      60 min respectively, operated twice, resulted in 99.9% volatilization of Si.
      Matrix free solutions were analyzed for impurities using DRC-ICP-MS. The
      recoveries of Cr, Mn, Fe, Ni, Co, Cu, Zn, Sr, Y, Cd, Ba and Pb were between 80
      and 100% after volatilization of Si. The blanks were in lower ng g(-1) with
      method detection limits in lower ng g(-1) to sub n gg(-1) range. The method was
      applied for the analysis of two silicon nitride samples.

PMID- 18036376
TI  - Classification of multiway analytical data based on MOLMAP approach.
AB  - A new method for the study of molecule chemical information organized into three
      way data structures (MOLMAP) was recently proposed in literature. Basically,
      MOLMAP molecular fingerprints are calculated by projecting bond properties of
      molecules into Kohonen networks and used to generate molecular descriptors for
      QSAR modeling. Since this technique has never been applied to other kinds of
      chemical multiway data, in this study classification models were carried out by
      means of MOLMAP approach on three-way analytical datasets of electronic nose and
      fluorescence data. For comparing purposes, other classification methods were
      applied to the same datasets: Discriminant Analysis on the PARAFAC scores and
      Partial Least Square-Discriminant Analysis (PLS-DA) on the unfolded data. Since
      the MOLMAP approach provided good results for the analyzed datasets, here, we
      propose the MOLMAP approach to be used as a general technique for the
      classification of multiway datasets. Actually, besides the good classification
      performances, other advantages came out: (a) the MOLMAP scores appeared as
      effective fingerprints for data characterization; (b) the role and importance of
      each portion of the multiway data can be analyzed in a comprehensive way; (c) it
      is possible to understand which variables have greater discriminant power and
      consequently apply data reduction.

PMID- 18036377
TI  - Determination of organophosphorous pesticides in wastewater samples using binary
      solvent liquid-phase microextraction and solid-phase microextraction: a
      comparative study.
AB  - A simple and efficient binary solvent-based two-phase hollow fiber membrane (HFM)
      protected liquid-phase microextraction (BN-LPME) technique for moderately polar
      compounds was developed. Six organophosphorous pesticides (OPPs)
      (triethylphosphorothioate, thionazin, sulfotep, phorate, disulfoton, methyl
      parathion and ethyl parathion) were used as model compounds and extracted from 10
      mL wastewater with a binary-solvent (toluene:hexane, 1:1) mixture. Some important
      extraction parameters, such as extraction time, effect of salt, sample pH and
      solvent ratio composition were optimized. BN-LPME combined with gas
      chromatography/mass spectrometric (GC/MS) analysis provided repeatability
      (R.S.D.s < or = 12%, n = 4), and linearity (r < or = 0.994) and solid-phase
      microextraction provides comparable of R.S.D.s < or = 13%, n = 4 and linearity (r
      < or = 0.966) for spiked water samples. The limits of detection (LODs) were in
      the range of 0.3-11.4 ng L(-1) for BN-LPME and 3.1-120.5 ng L(-1) for SPME at
      (S/N = 3) under GC/MS selective ion monitoring mode. In addition to high
      enrichment, BN-LPME also served as a sample cleanup procedure, with the HFM act
      as a filtering medium to prevent large particles and extraneous materials from
      being extracted. To investigate and compare their applicability, the BN-LPME and
      SPME procedures were applied to the detection of OPPs in domestic wastewater
      samples.

PMID- 18036378
TI  - Quantitative bioanalysis of quinine by atmospheric pressure-matrix assisted laser
      desorption/ionization mass spectrometry combined with dynamic drop-to-drop
      solvent microextraction.
AB  - Dynamic drop-to-drop solvent microextraction (DDSME) combined with atmospheric
      pressure-matrix assisted laser desorption/ionization mass spectrometry (AP
      MALDI/MS) has been successfully applied on the bioanalysis of quinine using micro
      liter volume (30 microL) of human urine and plasma samples. The method is based
      on the movement of aqueous phase (AP) in and out of the microsyringe, which
      increases the transfer and diffusion rate of the quinine drug from aqueous phase
      to organic phase (OP). The optimization parameters including the effect of
      solvent selection, number of samplings, sampling volume, volume of aqueous phase,
      volume of organic phase, addition of salt and pH were investigated for obtaining
      higher extraction efficiency of the analyte. The limits of detections (LODs) of
      quinine, using the dynamic DDSME/AP-MALDI/MS in urine and plasma samples were
      0.18 and 0.24 microM, respectively. The superiority of dynamic DDSME over static
      DDSME and liquid-liquid extraction (LLE) was also demonstrated for the
      determination of quinine in aqueous solution. This method is promising in
      clinical application and pharmacokinetic studies, in which the availability of
      sample amount is extremely small.

PMID- 18036379
TI  - Headspace solid-phase microextraction using an electrochemically deposited
      dodecylsulfate-doped polypyrrole film to determine of phenolic compounds in
      water.
AB  - A dodecylsulfate-doped polypyrrole (PPy-DS) film was prepared by electrochemical
      fiber coating (EFC) technique and applied as a new fiber for headspace solid
      phase microextraction (HS-SPME) of phenolic compounds from water samples.
      Electrochemically polymerized PPy is formed on the surface of a platinum wire and
      will contain charge-compensating anion (dodecylsulfate) incorporated during
      synthesis. The efficiency of this fiber for microextraction of phenols was
      evaluated using a HS-SPME device coupled with gas chromatography-flame ionization
      detection (GC-FID). The results shows that PPy-DS as a SPME fiber coating is
      suitable for the successful extraction of phenolic compounds. Parameters like
      ionic strength, agitation of the sample, sample pH, temperature of the sample,
      and adsorption/desorption times were studied and optimized to obtain the best
      extraction results. This method provided good repeatability (R.S.D.s<7.2%) for
      spiked water samples. The calibration graphs were linear in the range of 2-100 ng
      mL(-1) with the square of the correlation coefficient R2>0.991 and detection
      limits were between 0.57 and 1.82 ng mL(-1). The capability of PPy-DS to extract
      phenolic compounds has been compared with the results obtained with literature
      data for several fibers and this laboratory-made fiber showed comparable
      analytical parameter for the studied compounds.

PMID- 18036380
TI  - Capillary scale light emitting diode based multi-reflection absorbance detector.
AB  - We describe a light emitting diode (LED) based multi-reflection capillary scale
      absorbance detector based on both square and round capillaries and compare their
      performance with a conventional single-pass on-tube detector. The optical path
      length is extended by silver coating, the external surface of the capillary. The
      reflective geometry has been reported to be less prone to artifacts induced by
      refractive index changes; we do find this to be true. Although the detection
      volume/illuminated volume is increased some, a multi-reflection cell based on a
      180 microm bore capillary with a approximately 2-cm long illuminated volume shows
      over a 50-fold gain in signal-to-noise (S/N) compared to a single-pass on-tube
      configuration with the same capillary. The limit of detection (LOD) is 4.4 fmol
      (2.6 pg, 1 microL of 22.0 nM injected dye) BTB under pulseless (pneumatic) flow
      conditions. The cells behave as multipath devices where the effective path
      lengths are greater at low absorbance values. In our experiments, where non
      coherent light is launched through optical fibers that are large compared to
      capillary bore dimensions, increase in the effective path length of the cell do
      not occur in a predictable fashion with the angle of incidence of the light beam.
      Although the effective path length almost linearly increases with increasing
      distance between the light entry and exit windows, the absolute values of the
      effective path lengths are always lower than this physical distance, suggesting
      that after some passage through the solution, light largely travels through or
      along the glass wall. Square capillaries have better light transmission and offer
      some performance advantages. Multi-reflection cells can indeed be of value for
      sensitive detection in microflow systems.

PMID- 18036381
TI  - Electroosmotically driven capillary transport of typical non-Newtonian biofluids
      in rectangular microchannels.
AB  - In this paper, a detailed theoretical model is developed for studying the
      capillary filling dynamics of a non-Newtonian power-law obeying fluid in a
      microchannel subject to electrokinetic effects. Special attention is devoted to
      model the effects of the electroosmotic influences in the capillary advancement
      process, variable resistive forces acting over different flow regimes, and the
      dynamically evolving contact line forces, in mathematically closed forms. As an
      illustrative case study, in which the flow parameters are modeled as functions of
      the hematocrit fraction in the sample, the capillary dynamics of a blood sample
      are analyzed. Flow characteristics depicting advancement of the fluid within the
      microfluidic channel turn out to be typically non-linear, as per the relative
      instantaneous strengths of the capillary forces, electroosmotic forces and
      viscous resistances. Non-trivial implications of the blood hematocrit level and
      the imposed electric field on the progression of the capillary front are
      highlighted, which are expected to be of significant consequence towards the
      dynamics of electroosmotically aided capillary filling processes of biofluidic
      samples.

PMID- 18036382
TI  - Fluorimetric determination of phytic acid in urine based on replacement reaction.
AB  - A sensitive fluorimetric method for determination of phytic acid in human urine
      samples was described. The method was based on a fluorimetric replacement
      reaction, in which the added phytic acid replaced the Cu2+ ion from Cu2+-gelatin
      complex, liberating the fluorescent gelatin molecule. The fluorescence of the
      solution was accordingly recovered proportionally to the amount of the foreign
      phytic acid. The excitation wavelength was 273.5 nm and the characteristic
      emission wavelength was 305.0 nm, respectively. The calibration graph was
      obtained by plotting the recovered fluorescent intensity at maximum 305.0 nm
      against the added standard phytic acid, and was divided into two sections. One
      section was linear over the range of 0.40-2.40 mg L(-1) with a linear regression
      equation of I(f) = -0.895+15.146c (R2 > 0.9993), and the other over the range of
      2.40-9.20 mg L(-1) with a linear regression equation of I(f) = -29.526+26.113c
      (R2 > 0.9996), respectively. The relative standard deviation (R.S.D.) at 95%
      confidence degree for a 2.0 mg L(-1) of standard phytic acid within 1 month was
      less than 1.26% (n = 5), indicating the procedure is reproducible. The detection
      and the quantification limits of phytic acid were estimated to be 0.23 and 0.40
      mg L(-1), respectively. The proposed method was applied to the determination of
      phytic acid in urine samples and the found concentrations of phytic acid in urine
      were in the range of 0.49-0.75 mg L(-1) with recoveries of 96.2-108.8%.
      Comparison of the obtained results with the reported HPLC was performed,
      indicating the proposed method was reliable.

PMID- 18036383
TI  - Synthesis and applications of surface-grafted Th(IV)-imprinted polymers for
      selective solid-phase extraction of thorium(IV).
AB  - A new functional monomer N-(o-carboxyphenyl)maleamic acid (CPMA) was synthesized
      and chosen for the preparation of surface-grafted ion-imprinted polymers (IIPs)
      specific for thorium(IV). Polymerizable double bond was introduced to silica gel
      surface by amidation reaction between -NH2 and maleic anhydride. In the ion
      imprinting process, thorium(IV) was complexed with the carboxyl groups, then was
      imprinted in the polymers grafted to the silica gel surface. The imprinted Th(IV)
      was removed with 3 mol L(-1) HCl. The obtained imprinted particles exhibited
      excellent selectivity and rapid kinetics process for Th(IV). The relatively
      selective factor (alpha(r)) values of Th(IV)/La(III), Th(IV)/Ce(III),
      Th(IV)/Nd(III), Th(IV)/U(VI), and Th(IV)/Zr(IV) were 85.7, 88.9, 26.6, 64.4, and
      433.8, respectively, which were greater than 1. The precision (R.S.D.), the
      detection limit (3sigma), and the quantification limit (10sigma) of the method
      were 1.9%, 0.51 ng mL(-1) and 1.19 ng mL(-1), respectively. The prepared IIPs as
      solid-phase extractants were successfully applied for the preconcentration of
      trace thorium in natural and certified samples prior to its determination by
      inductively coupled plasma atomic emission spectrometry (ICP-AES) with
      satisfactory results.

PMID- 18036384
TI  - Acid-catalyzed isomerization and decomposition of ketone-2,4
      dinitrophenylhydrazones.
AB  - The quantitative analysis of ketones using DNPH is usually conducted in the
      presence of an acid catalyst. However, this method may cause an analytical error
      because 2,4-dinitrophenylhydrazones have both E- and Z-stereoisomers. Purified
      ketone-2,4-dinitrophenylhydrazone comprised only the E-isomer. However, under the
      addition of acid, both E- and Z-isomers were seen. In the case of 2-butanone-, 2
      pentanone- and 2-hexanone-2,4-dinitrophenylhydrazone, the equilibrium Z/E isomer
      ratios were 0.20, 0.21 and 0.22, respectively. In addition, when trace water was
      added to the hydrazone derivatives in acetonitrile solution, the concentration of
      ketone derivatives were seen to decrease and the concentration of free DNPH was
      seen to increase. The decomposition rate of 2-butanone-2,4-dinitrophenylhydrazone
      was dependent on the concentration of acid-catalysis and reached an equilibrium
      state--carbonyl, DNPH, hydrazone-derivative and H2O--within 10 h at 0.1 mol L(-1)
      phosphoric acid solution. The equilibrium constants of ketone-2,4
      dinitrophenylhydrazones, [carbonyl] [DNPH]/[hydrazone] [H2O], were relatively
      large and ranged from 0.74x10(-4) to 5.9x10(-4). Hydrazone derivatives formed
      from 2-ketones such as 2-pentanone, 2-hexanone and 4-methyl-2-pentanone showed
      lower equilibrium constants than corresponding 3-ketones. Consequently, only a
      minimum concentration of catalytic acid must be added. The best method for the
      determination of ketone-2,4-dinitrophenylhydrazones by HPLC or GC is to add
      phosphoric acid to both the standard reference solution and samples, forming a
      0.001 mol L(-1) acid solution, and analyze after 27 h.

PMID- 18036386
TI  - Too many notes: up and down the scales of diabetes therapy.

PMID- 18036385
TI  - Simultaneous determination of L-arginine and 12 molecules participating in its
      metabolic cycle by gradient RP-HPLC method: application to human urine samples.
AB  - We have developed and described a highly sensitive, accurate and precise reversed
      phase high-performance liquid chromatography (RP-HPLC) method for the
      simultaneous determination of L-arginine and 12 molecules participating in its
      metabolic cycle in human urine samples. After pre-column derivatization with
      ortho-phthaldialdehyde (OPA) reagent containing 3-mercaptopropionic acid (3MPA),
      the fluorescent derivatives were separated by a gradient elution and detected by
      fluorescence measurement at 338 nm (excitation) and 455 nm (emission). L-Arginine
      (ARG) and its metabolites: L-glutamine (GLN), N(G)-hydroxy-L-arginine (NOHA), L
      citrulline (CIT), N(G)-monomethyl-L-arginine (NMMA), L-homoarginine (HARG),
      asymmetric N(G),N(G)-dimethyl-L-arginine (ADMA), symmetric N(G),N(G')-dimethyl-L
      arginine (SDMA), L-ornithine (ORN), putrescine (PUT), agmatine (AGM), spermidine
      (SPERMD) and spermine (SPERM) were extracted in a cation-exchange solid-phase
      extraction (SPE) column and after derivatization separated in a Purospher STAR RP
      18e analytical column. The calibration curves of analysed compounds are linear
      within the range of concentration: 45-825, 0.2-15, 16-225, 12-285, 0.1-32, 15
      235, 0.1-12, 0.1-12, 10-205, 0.02-12, 0.1-24, 0.01-10 and 0.01-8 nmol mL(-1) for
      GLN, NOHA, CIT, ARG, NMMA, HARG, ADMA, SDMA, ORN, PUT, AGM, SPERMD and SPERM,
      respectively. The correlation coefficients are greater than 0.9980. Coefficients
      of variation are not higher than 6.0% for inter-day precision. The method has
      been determined or tested for limits of detection and quantification, linearity,
      precision, accuracy and recovery. All detection parameters of the method
      demonstrate that it is a reliable and efficient means of the comprehensive
      determination of ARG and its 12 main metabolites, making this approach suitable
      for routine clinical applications. The levels of analysed compounds in human
      urine can be successfully determined using this developed method with no matrix
      effect.

PMID- 18036387
TI  - Advancing therapy in type 2 diabetes mellitus with early, comprehensive
      progression from oral agents to insulin therapy.
AB  - BACKGROUND: Early and intensive glycemic control is necessary to prevent or
      minimize the development of microvascular and macrovascular complications in
      individuals with type 2 diabetes mellitus. However, many patients are unable to
      attain glycemic control, partly due to protracted treatment with oral
      antidiabetic drugs (OADs) despite inadequate control and barriers to initiating
      insulin therapy. Patients at different stages of disease may benefit from the
      early introduction of intensive glycemic control. OBJECTIVE: This article
      discusses some of the potential barriers to achieving and maintaining optimal
      glycemic levels in patients whose blood glucose is sub-optimally controlled with
      OADs and reviews the benefits of early introduction of intensive glycemic control
      in patients at various stages of disease, with an emphasis on insulin therapy.
      METHODS: Relevant English-language articles published from 1996 to 2006 were
      identified through searches of the National Center for Biotechnology PubMed
      database. Search terms included insulin, insulin therapy, type 2 diabetes,
      insulin analogs, early insulinization, and diabetes prevention, among others.
      Studies were assessed regarding designs, primary and secondary efficacy
      parameters, glycosylated hemoglobin (HbAM(lc)), fasting plasma glucose, incidence
      of hypoglycemia, and other safety assessments. Inclusion criteria were
      multicenter, randomized, open-label, parallel-group trials, as well as
      retrospective observational studies, conducted in Europe or the United States.
      Additional analyses and guideline-based recommendations are included. RESULTS:
      The landmark results of the United Kingdom Prospective Diabetes Study, which
      found that an intensive strategy in 3867 newly diagnosed patients with type 2
      diabetes was associated with stricter glycemic control than was conventional care
      (HbA(lc) over 10 years, 7.0% vs 7.9%; P < 0.001), as well as a 25% reduction in
      the risk for microvascular complications (P = 0.01). Early initiation of insulin
      therapy concomitantly with OADs appeared well tolerated in the populations
      studied, was effective in recently diagnosed patients, and may also confer anti
      inflammatory and antiatherogenic effects. Characteristics associated with newer
      formulations of insulin (eg, basal insulin analogues as well as rapid-acting
      insulin analogues, the insulin pump, or inhaled insulin) may help overcome
      barriers associated with initiating insulin therapy. CONCLUSIONS: Based on the
      literature, early and persistent intensification of antidiabetic therapy is an
      approach that most likely will achieve optimal glycemic control in patients with
      type 2 diabetes and help prevent associated complications. Greater clinical
      experience with newer therapeutic approaches, including incretin mimetics and
      dipeptidyl peptidase-IV inhibitors, will provide insight into their place in the
      spectrum of diabetes treatments.

PMID- 18036388
TI  - Prandial premixed insulin analogue regimens versus basal insulin analogue
      regimens in the management of type 2 diabetes: an evidence-based comparison.
AB  - BACKGROUND: Insulin is an effective treatment for type 2 diabetes (T2D), a
      progressive condition in which insulin deficiency is one of the core defects.
      When patients with T2D are unable to achieve glycemic goals with diet and oral
      antihyperglycemic medications, a common starting insulin regimen consists of
      basal or premixed insulin added to oral antihyperglycemic medications. When
      glycemic goals are not achieved with the initial insulin regimen, a basal-bolus
      regimen is necessary. OBJECTIVE: This article reviews clinical-trial data on the
      efficacy and safety profile of prandial premixed insulin analogues (insulin
      aspart and insulin lispro) compared with basal insulin analogues (insulin
      glargine, insulin detemir, and insulin lispro protamine suspension), with or
      without a prandial insulin analogue, in the management of T2D. METHODS: A
      systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to
      identify published randomized controlled trials comparing prandial premixed
      insulin analogues with basal insulin analogues, with or without prandial insulin,
      in patients with T2D. The search terms were premixed insulin analogues, premixed
      insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50,
      premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine,
      and detemir. Abstracts presented at the 2005 and 2006 meetings of the American
      Diabetes Association and the European Association for the Study of Diabetes and
      bibliographies of the identified studies were also reviewed. Predetermined
      criteria for study inclusion were treatment duration of at least 12 weeks, T2D
      diagnosed using valid criteria, use of a basal insulin analogue (with or without
      rapid-acting insulin) as a study comparator, and use of well-accepted end points
      (eg, glycosylated hemoglobin [HbA(1c)], hypoglycemia, preprandial and
      postprandial blood glucose). RESULTS: Of the identified randomized controlled
      trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal
      and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only,
      and 3 studies evaluated premixed insulin analogues containing 50% basal and 50%
      rapid-acting insulin analogue with basal insulin analogues only. Use of prandial
      premixed insulin analogues was associated with better overall and postprandial
      glycemic control. In the studies that compared twice-daily premixed insulin
      analogues with a basal insulin analogue, changes in HbA(1c) ranged from -1.00% to
      -2.79% and from -0.42% to -2.36%, respectively (P < 0.01). In the studies that
      compared thrice-daily premixed insulin analogues with a basal insulin analogue,
      changes in HbA(1c) ranged from -0.72% to -1.2% and from -0.3% to -0.75%,
      respectively (P < 0.01). These results were achieved with some increase in
      overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the
      premixed insulin analogues were adjusted during the titration period to achieve
      glycemic goals. CONCLUSIONS: The results of this systematic review suggest that
      regimens consisting of prandial premixed insulin analogues, which provide both
      basal and prandial insulin coverage, may be used as an initial insulin regimen in
      patients with T2D to enable better overall, preprandial, and postprandial
      glycemic control compared with a basal insulin analogue regimen alone. Premixed
      insulin analogues are an effective option for initiating and intensifying insulin
      therapy in patients with T2D.

PMID- 18036389
TI  - Developing a pulmonary insulin delivery system for patients with diabetes.
AB  - BACKGROUND: Many patients with type 1 or type 2 diabetes mellitus (DM) do not
      achieve recommended glycemic goals. Insulin therapy is often delayed, despite its
      effectiveness in maintaining glycemic control, for reasons such as fear of
      needles or dislike of the complexity of injections. Inhaled dry powder insulin
      (IDPI) is approved for preprandial use in both the United States and Europe.
      METHODS: Relevant English-language publications were identified through a search
      of the PubMed data-base (1980-2007). Search terms included diabetes, in
      combination with subcutaneous and/or inhaled insulin. A similar search of
      abstracts from the 2006 American Diabetes Association 66th Annual Scientific
      Sessions was also performed. RESULTS: Eight clinical studies to date have
      reported that IDPI consistently improved glycemic control, whether used in
      combination with longer-acting SC insulin regimens in patients with type 1 or
      type 2 DM or to supplement or replace oral agent therapy in patients with type 2
      DM. Evidence to date suggests that IDPI is associated with an acceptable
      tolerability profile, with a risk of hypoglycemia similar to that of SC insulin
      (risk ratios in 2 studies were 0.94 and 0.96, in favor of IDPI). Moreover, no
      clinically significant changes in pulmonary function have been noted. Patients
      treated with IDPI in clinical studies reported significantly greater improvements
      in overall satisfaction with treatment compared with SC insulin (P < 0.01) or
      oral agent therapy (P= 0.02). CONCLUSION: IDPI is effective and well tolerated
      for the treatment of diabetes and may be an option for patients to achieve
      glycemic control.

PMID- 18036390
TI  - Importance of observational studies in clinical practice.
AB  - BACKGROUND: In this era of evidence-based medicine, clinicians require a
      comprehensive range of well-designed studies to support prescribing decisions and
      patient management. In recent years, data from observational studies have become
      an increasingly important source of evidence because of improvements in
      observational-study methods and advances in statistical analysis. OBJECTIVE: This
      article reviews the current literature and reports some of the key studies
      indicating that observational studies can both complement and build on the
      evidence base established by randomized controlled trials (RCTs). METHODS: A
      literature search using the MEDLINE/PubMed database (years: 1966-present) was
      carried out using the search terms observational or observational study(ies),
      historical control, nonrandomized, and postmarketing surveillance. All references
      comparing observational studies with randomized controlled trials were obtained
      and reviewed and were also hand-checked for studies not identified in the
      database searches. RESULTS: Observational studies play an important role in
      investigating treatment outcomes. Data from large observational studies can
      clarify the tolerability profile of marketed medicines. In particular,
      observational studies can be of benefit in the study of large, heterogeneous
      patient populations with complex, chronic diseases such as diabetes mellitus.
      Observational studies have played a key role in supporting the results of Phase
      III studies of insulin analogues for the treatment of patients with type 1 and
      type 2 diabetes. Future observational studies in the field of diabetes such as
      PREDICTIVE (Predictable Results and Experience in Diabetes through
      Intensification and Control to Target: an International Variability Evaluation)
      and IMPROVE will further our understanding of this global pandemic. CONCLUSIONS:
      Well-designed observational studies can play a key role in supporting the
      evidence base for drugs and therapies. Current evidence suggests that
      observational studies can be conducted using the same exacting and rigorous
      standards as are used for RCTs. The observational study design should be
      considered as a complementary rather than a rival analytic technique.

PMID- 18036391
TI  - Health care costs and medication adherence associated with initiation of insulin
      pen therapy in Medicaid-enrolled patients with type 2 diabetes: a retrospective
      database analysis.
AB  - BACKGROUND: Clinical, health, and economic outcomes in patients with type 2
      diabetes may be influenced by self-management behaviors and type of
      pharmacotherapy. OBJECTIVE: This study examined differences in medication
      adherence and total health care costs among patients with type 2 diabetes who
      initiated or converted to insulin administration with a pen device in comparison
      with a vial/syringe as add-on therapy to oral antidiabetic drugs. METHODS: This
      study evaluated patients with type 2 diabetes who were enrolled in the North
      Carolina Medicaid program from September 24, 2001, to July 18, 2006. Patients
      receiving insulin with a vial/syringe who converted to pen therapy were compared
      with those who remained on vial/syringe in both unmatched comparisons (n = 560
      and n = 9988, respectively) and after pair-matching (both cohorts, n = 560) with
      the use of propensity scores. In a second analysis, patients who initiated
      insulin with vial/syringe (n = 1162) were compared with a cohort that initiated
      insulin pen therapy (n = 168) after controlling for covariates in a multivariate
      regression model. All included patients had complete enrollment for at least 24
      months of follow-up. Multiple linear regression models were used to predict the
      comparative impact on total health care costs and medication adherence for each
      cohort. Adjusted means were calculated to determine the group differences for
      each outcome. RESULTS: Diabetes-related and overall medication adherence was
      comparable for patients initiating insulin with a pen versus a syringe (53% vs
      50% and 94% vs 94%, respectively). However, total annualized health care costs
      were significantly lower for patients using pen therapy than for those using a
      syringe ($14,857.42 vs $31,764.78, respectively; P < 0.05). Cost reductions with
      pen therapy were reflected in hospital costs ($1195.93 vs $4965.31, respectively;
      P < 0.05), diabetes-related costs ($7324.37 vs $13,762.21, respectively; P <
      0.05), and outpatient costs ($7795.98 vs $13,103.51, respectively; P < 0.05).
      However, prescription costs of syringe were significantly lower ($535.70 vs
      $670.52; P < 0.05) and costs of pen were higher ($840.33 vs $0; P < 0.05) in
      patients who were switched from syringe to pen versus those who remained on
      syringe therapy. CONCLUSIONS: In a state Medicaid setting among patients with
      type 2 diabetes, initiating insulin therapy with a pen device was associated with
      comparable medication adherence and significant reductions in health care
      resource utilization and associated costs compared with vial/syringe insulin.
      Health care professionals and policy makers should consider the potential
      economic benefits of pen therapy when initiating insulin among Medicaid
      beneficiaries who fail to respond to oral antidiabetic drugs.

PMID- 18036392
TI  - Comparisons of rosiglitazone versus pioglitazone monotherapy introduction and
      associated health care utilization in Medicaid-enrolled patients with type 2
      diabetes mellitus.
AB  - BACKGROUND: Outcomes in patients with type 2 diabetes mellitus (DM) can differ
      based on the antidiabetic medication that is used. Thiazolidinediones (TZDs) are
      a newer class of agents used for the treatment of type 2 DM. No previous study
      has compared health care utilization associated with the 2 TZDs on the market.
      OBJECTIVE: The objective of this study was to compare health care utilization and
      costs associated with initiation of treatment with either rosiglitazone or
      pioglitazone by Medicaid-enrolled patients with type 2 DM. METHODS: This was a
      retrospective data analysis comparing cohorts of patients with type 2 DM starting
      a new antidiabetic medication in terms of hospitalizations, emergency department
      visits, outpatient physician visits, and health care costs reimbursed by the
      North Carolina Medicaid program. The perspective adopted in this analysis was
      that of the third-party payer (ie, the North Carolina Medicaid program). Patients
      starting rosiglitazone between July 1, 2001, and June 30, 2002, were compared
      with patients starting pioglitazone during the same period. The patients were
      followed up for 30 months to examine the difference in health care utilization
      over time. Multivariate regression techniques were employed for comparisons
      between the 2 different antidiabetic therapies. RESULTS: A total of 1705 patients
      with type 2 DM were identified and included in the final cohort. There were 660
      patients (mean [SD] age, 49.0 [10.2] years) in the rosiglitazone arm and 1045
      patients (mean [SD] age, 49.1 [10.5] years) in the pioglitazone arm. Multivariate
      analysis showed that the rosiglitazone monotherapy group was associated with a
      12.2% decrease in the mean number of hospitalizations, a 10.4% decrease in the
      mean number of emergency department visits, and a 7.3% decrease in total health
      care costs compared with the pioglitazone monotherapy group (all, P < 0.05). This
      study only looked at patients who used the same drug for the entire follow-up
      period. It did not account for drug switching or addition of a new drug to an
      existing therapy. CONCLUSIONS: Introduction of rosiglitazone was associated with
      a decreased number of hospitalizations, emergency department visits, and total
      health care costs compared with pioglitazone. The utilization of oral
      antidiabetic agents, with documented clinical and economic benefits, should
      continue to be advocated to reduce avoidable medical care utilization and to
      improve patient outcomes in this population.

PMID- 18036393
TI  - Health care costs and mortality for Canadian urban and rural patients with
      diabetes: population-based trends from 1993-2001.
AB  - BACKGROUND: Recent reports suggest that the health status of individuals residing
      in rural areas (as much as one third of the Canadian population) may be inferior
      to those who live in urban areas. OBJECTIVE: This study compared trends in
      mortality and in provincial health care system costs for individuals with
      diabetes, according to urban/rural residence in Saskatchewan, Canada. METHODS:
      The Canadian National Diabetes Surveillance System criteria were applied to the
      linked administrative databases of Saskatchewan Health to identify all
      individuals with diabetes between 1991 and 2001. Annual health care costs across
      5 categories of health care services (physician visits, prescription medications,
      hospitalizations, day surgeries, and dialysis) were identified over a 9-year
      period (1993-2001). Costs (in 2001 Can $) and mortality rates were directly age
      adjusted, and comparisons were made across individuals residing in large urban,
      small urban, and rural areas. RESULTS: A total of 57,774 individuals with
      diabetes were identified, approximately half (n = 26,656) of whom resided in
      rural areas. In 2001, total per capita costs were $3454 for large urban, $3427
      for small urban, and $3289 for rural dwellers. Per capita costs of most
      individual categories were highest in large urban centers over the follow-up
      period with the exception of hospitalizations, which were highest among rural
      residents ($1444 vs $1283 for large urban residents). Despite differences in the
      individual cost categories, overall health care costs according to place of
      residence were similar. Overall, the age-adjusted mortality rates increased
      substantially from 12 (1993) to 18 (2001) deaths per 1000 population, although
      rates were similar across geographic locations. CONCLUSIONS: From 1993 to 2001,
      we observed systematic differences in costs of individual resource categories
      according to urban/rural residence in Saskatchewan, with urban dwellers with
      diabetes incurring greater costs in most categories. Age-adjusted total costs and
      mortality rates were similar, however, suggesting that rural populations with
      diabetes may not be as disadvantaged as commonly believed. Investing in better
      primary care access for all patients with diabetes may reduce downstream costs in
      Saskatchewan's provincial health care system.

PMID- 18036394
TI  - A carrier of both MEN1 and BRCA2 mutations: case report and review of the
      literature.
AB  - High-penetrance autosomal dominant cancer susceptibility genes such as BRCA2 and
      MEN1 result in specific patterns of cancers in individuals who inherit germline
      mutations. Their incidence in the population is relatively low, however, and it
      is highly unusual to identify individuals with two or more inherited cancer gene
      mutations. We describe a family with multiple cases of MEN1-associated cancers as
      well as pancreatic adenocarcinoma, ovarian cancer, and male breast cancer, in
      which we identified germline mutations in both MEN1 and BRCA2. To our knowledge,
      this is the first report of a patient with both MEN1 and BRCA2 mutations and with
      a personal history of hyperparathyroidism and pancreatic neuroendocrine tumors.

PMID- 18036395
TI  - Establishment and molecular cytogenetic characterization of non-small cell lung
      cancer cell line KU-T1 by multicolor fluorescence in situ hybridization,
      comparative genomic hybridization, and chromosome microdissection.
AB  - A human lung adenocarcinoma cell line, designated KU-T1, was established from a
      Japanese man in Kochi Medical School. Conventional banding and multicolor
      fluorescence in situ hybridization (M-FISH) analyses of KU-T1 cells revealed a
      hyperdiploid chromosomal constitution and complex karyotypes. Comparative genomic
      hybridization showed several chromosomal copy number changes, and five regions
      that were highly amplified. Two of the five highly amplified regions, 1q and 3q,
      were identified from distributions of DNA sequences on a metaphase cell by FISH
      using chromosome microdissection-generated probes hybridized to 1q32
      approximately q34 and 3q26 approximately q28, respectively. The 3q probe depicted
      a homogeneously staining region (hsr) in a derivative chromosome 3 of KU-T1. An
      hsr probe was regenerated by chromosome microdissection and was hybridized back
      to KU-T1 and normal metaphases. This hybridization experiment confirmed the probe
      derived from an hsr and indicated original locations of DNA sequences of hsr on
      normal chromosome 3. Intense hybridized signals shown at three loci (3p12,
      3q26.3, and 3q28) suggests that oncogenes may be involved in the hsr formation.
      The present study provides a comprehensive analysis of the chromosomal
      abnormalities, including hsr formation and related oncogenes, in the KU-T1 cell
      line.

PMID- 18036396
TI  - Novel 6p rearrangements and recurrent translocation breakpoints in retinoblastoma
      cell lines identified by spectral karyotyping and mBAND analyses.
AB  - Gain of the short arm of chromosome 6, usually through isochromosome 6p
      formation, is present in approximately 50% of retinoblastoma tumors. The minimal
      region of gain maps to chromosome band 6p22. Two genes, DEK and E2F3, are
      implicated as candidate oncogenes. However, chromosomal translocations have been
      overlooked as a potential mechanism of activation of oncogenes at 6p22 in
      retinoblastoma. Here, we report combined spectral karyotyping), 4',6-diamidino-2
      phenylindole banding, mBAND, and locus-specific fluorescence in situ
      hybridization analyses of four retinoblastoma cell lines, RB1021, RB247c, RB383,
      and Y79. In RB1021 and RB247c, 6p undergoes structural rearrangements involving a
      common translocation breakpoint at 6p22. These data imply that 6p translocations
      may represent another mechanism of activation of 6p oncogene(s) in a subset of
      retinoblastomas, besides the copy number increase. In addition to 6p22, other
      recurrent translocation breakpoints identified in this study are 4p16, 11p15,
      17q21.3, and 20q13. Common regions of gain map to chromosomal arms 1q, 2p, 6p,
      17q, and 21q.

PMID- 18036397
TI  - Suppression of FasL expression in tumor cells and preventing tumor necrosis
      factor-induced apoptosis by adenovirus 14.7K is an effective escape mechanism for
      immune cells.
AB  - To elucidate if the Fas/FasL signal pathway participates in the immune escape of
      tumor cells, and if contemporary Fas/FasL and tumor necrosis factor (TNF))
      induced apoptosis is better for immune cell survival than just blocking Fas/FasL
      induced apoptotic signal. FasL expression in mouse H22 hepatocellular cancer
      cells was suppressed by the siRNA technique. The wild-type Ad5 14.7K gene was
      amplified by polymerase chain reaction and transduced into Jurkat T-cells.
      Apoptosis of target Jurkat cells was detected by flow cytometry. TNF-alpha in the
      culture supernatant of H22 cells by ELISA was seen. FasL and 14.7K gene
      expression in stably transfected or transduced clones were determined by Western
      blotting. As a result, FasL expression in H22 cells was down-regulated after
      stable transfection with a plasmid encoding antisense FasL cDNA. Down-regulation
      of FasL expression in H22 cells had no effect on tumor growth in vitro. There was
      an apparent decrease in the number of apoptotic Jurkat T-cells after coculture
      with transfected H22 cells, relative to coculture with FasL-expressing
      untransfected cells. Compared with untransduced Jurkat cells, apoptotic rates in
      14.7K-transduced Jurkat cells were significantly reduced in three different E/T
      ratios (P < 0.01), respectively. We conclude that Fas/FasL signal pathway
      participates in the immune escape of tumor cells by inducing immune cells
      apoptosis. Reducing the expression of FasL in tumor cells can decrease the
      apoptotic rate of immune cells, further blocking the apoptotic signal pathway of
      immune cells by preventing TNF-induced apoptosis can increase the survival of
      immune cells.

PMID- 18036398
TI  - Allelic imbalance at 13q14.2 approximately q14.3 in localized prostate cancer is
      associated with early biochemical relapse.
AB  - Allelic imbalance (AI), particularly at chromosomes 8p, 10q, and 13q, is the most
      frequently observed genetic change in sporadic prostate cancer. AI at these sites
      may inactivate tumor suppressor genes that regulate normal cell growth. To
      establish the relationship between AI and progression, we analyzed loci on 8p,
      10q, and 13q14 in archival prostate tumors matched for Gleason grade, pre
      operative prostate-specific antigen levels, and pathologic stage, and they were
      paired on the basis of relapse status after 3 years. AI was identified in 66% of
      patients without relapse and in 73% with relapse. There was no statistically
      significant difference for AI at 8p21.3 and 10q23.2 between the two groups of
      patients, but significant differences between relapsers and nonrelapsers in the
      frequency of AI at D13S165 at 13q14.2 (P=0.006) and D13S273 at 13q14.3 (P=0.03).
      There was also a significantly higher incidence of AI at both loci in the
      relapsers compared to the nonrelapsers (P=0.03). In three relapsers, AI occurred
      at all three loci between 13q14.2 and 13q14.3, with no nonrelapsers demonstrating
      AI at all three loci. These findings show that AI at 13q14.2 approximately q14.3
      is an important event in the progression of localized prostate cancer, and
      suggest a possible role for microRNAs.

PMID- 18036399
TI  - Confirmation of a novel recurrent association: BCR-ABL t(9;22) and t(19;21).
AB  - Association of a t(9;22)(q34;q11), BCR/ABL-positive, with a dic(19;21)(p13;p13)
      has been described in acute lymphoblastic leukemia in relapse, raising the
      question of whether this association is recurrent. Described here are two cases,
      one of myeloproliferative disease and one of acute lymphoblastic leukemia, both
      presenting a masked t(9;22) and t(19;21). Chromosomal rearrangements were
      ascertained by fluorescence in situ hybridization (FISH) using locus-specific
      probes, multicolor FISH, and bacterial artificial chromosome array. These
      additional observations suggest a nonrandom association.

PMID- 18036400
TI  - A der(1;15)(q10;q10) is a rare nonrandom whole-arm translocation in patients with
      acute lymphoblastic leukemia.
AB  - A rare karyotypic event, der(1;15)(q10;q10), which involves the whole long arms
      of chromosomes 1 and 15, has been reported in patients with various conditions,
      including acute myelogenous leukemia, myelodysplastic syndrome, polycythemia
      vera, and multiple myeloma. Only 27 cases of unbalanced der(1;15)(q10;q10) have
      been documented in the literature as single or complexed chromosomal
      abnormalities in hematological malignancies. Here, we describe two cases of acute
      lymphoblastic leukemia with der(1;15)(q10;q10), and review the previous reports.
      Although more case studies are needed, we suggest that der(1;15)(q10;q10) should
      be considered a nonrandom chromosomal abnormality in hematological malignancies
      including both lymphoid and myeloid neoplasms.

PMID- 18036401
TI  - Chromosomal rearrangements in lipofibromatosis.
AB  - Lipofibromatosis is a relatively rare pediatric neoplasm, which usually manifests
      as an ill-defined soft tissue mass involving the upper and lower distal
      extremities, the trunk, and, less frequently, the head. To date, no cytogenetic
      abnormalities have been reported in this uncommon neoplasm. We present a case of
      lipofibromatosis featuring a three-way t(4;9;6) translocation in a 5-year-old
      boy.

PMID- 18036402
TI  - DNA methylation patterns of the CDH1, RARB, and SFN genes in choroid plexus
      tumors.
AB  - Genetic and epigenetic alterations in choroid plexus tumors, a rare
      neuroepithelial neoplasm most frequently detected in children, are poorly
      characterized. Epigenetic silencing associated with aberrant CpG island
      methylation is one mechanism leading to the loss of tumor suppressor functions in
      cancer cells. Using methylation-specific polymerase chain reaction, the
      methylation patterns of the genes CDH1 (E-cadherin), RARB (retinoic acid
      receptor, beta), and SFN (stratifin; 14-3-3sigma) were retrospectively
      investigated in eight choroid plexus tumors (five papillomas, two atypical
      papillomas, and one carcinoma), as well as in two normal cortexes obtained after
      autopsy from male individuals aged 6 months and 64 years. Among the six pediatric
      tumors, the mean age at diagnosis was 1.8 years old (range, 0.2-6) and the two
      adult tumors were detected in a 66-year-old man and a 45-year-old woman. A high
      frequency of hypermethylation was detected in CDH1 and SFN genes in tumoral and
      normal cortex tissues. Tumor-specific RARB hypermethylation was observed in four
      papillomas. Further studies are required to evaluate the role of aberrant
      methylation in choroid plexus tumor progression.

PMID- 18036403
TI  - Cytogenetic and molecular cytogenetic findings of intimal sarcoma.
AB  - Intimal sarcomas are exceptionally rare tumors that arise from the tunica intima
      of large vessels. Most intimal sarcomas are high-grade tumors that exhibit
      fibroblastic or myofibroblastic differentiation. We report the cytogenetic
      findings of a tumor from a 57-year-old man. The tumor had a pleomorphic and
      spindle-cell morphology, and it also exhibited a complex karyotype that was
      characterized by several numeric and structural chromosomal abnormalities.
      Molecular cytogenetic analysis showed amplification of MDM2, SAS, and CDK4, but
      not of HMGA2, ATF1, or DDIT3, which supported the findings of a previous
      comparative genomic hybridization study. Further studies are needed to determine
      whether the cytogenetic abnormalities found in this case are recurrent events for
      this poorly characterized malignancy.

PMID- 18036404
TI  - Dedifferentiated liposarcoma of the pleura mimicking a malignant solitary fibrous
      tumor and associated with dedifferentiated liposarcoma of the mediastinum:
      usefulness of cytogenetic and molecular genetic analyses.
AB  - Dedifferentiated liposarcoma of the pleura is an extremely rare malignancy
      mimicking a variety of tumors, such as other sarcomas, mesothelioma, and
      malignant solitary fibrous tumor of the pleura. Liposarcoma of the pleura can be
      combined with mediastinal involvement, and in most cases it may be impossible to
      be certain where the primary tumor originated. In this report, we describe a very
      rare occurence of a dedifferentiated liposarcoma of the pleura in a 76-year-old
      woman associated with a distinct second dedifferentiated liposarcoma of the
      mediastinum. Histologically, the pleural tumor demonstrated spindle cells
      arranged in a fascicular pattern, whereas the mediastinal tumor was mostly
      adipocytic with small areas of spindle cells. Vimentin and protein S100 were
      focally expressed by the tumor cells. The differential diagnosis of the pleural
      mass included malignant solitary fibrous tumor. Cytogenetic analysis showed
      supernumerary ring chromosomes in the pleural tumor, as well as strong
      amplification of MDM2 and CDK4 genes in both tumors. Array comparative genomic
      hybridization showed amplifications of chromosome arms 6q, 12q, and 15q, shared
      by both tumors and strongly pointing to a common origin.

PMID- 18036405
TI  - The short arm of chromosome 18 is a recurrent integration site of a supernumerary
      BCR/ABL gene fusion in chronic myeloid leukemia.

PMID- 18036406
TI  - Translocation 3;21, trisomy 8, and duplication of the Philadelphia chromosome: a
      rare but recurrent cytogenetic pathway in the blastic phase of chronic myeloid
      leukemia.

PMID- 18036407
TI  - Mesenteric chloroma with t(16;16) followed by acute myelomonocytic leukemia with
      clonal evolution.

PMID- 18036408
TI  - A novel t(3;19)(p21;p13) in a patient with acute myelocytic leukemia.

PMID- 18036409
TI  - Systematic review of factors contributing to penicillin treatment failure in
      Streptococcus pyogenes pharyngitis.
AB  - OBJECTIVE: Review the evidence for various explanations for microbiologic
      treatment failure following use of penicillin in group A streptococcal (GAS)
      tonsillopharyngitis. DATA SOURCE: Systematic review of the literature based on
      Medline and EMBASE searches, and review of reference lists of included studies.
      RESULTS: The explanations for penicillin treatment failure in GAS
      tonsillopharyngitis include 1) carrier state, 2) lack of compliance, 3) recurrent
      exposure, 4) in vivo copathogenicity of beta-lactamase-producing normal
      pharyngeal flora, 5) in vivo bacterial coaggregation, 6) poor antibiotic
      penetration to tonsillopharyngeal tissue, 7) in vivo eradication of normal
      protective flora, 8) early initiation of antibiotic therapy resulting in
      suppression of an adequate host immune response, 9) intracellular localization of
      GAS, 10) GAS tolerance to penicillin, 11) contaminated toothbrushes or
      orthodontic appliances, and 12) transmission from the family pet. There is very
      little type I or II evidence to support any of the above-cited explanations for
      treatment failure in GAS tonsillopharyngitis; available studies are mostly
      observational (in patients) or laboratory-based without clinical confirmation.
      CONCLUSION: Multiple explanations have been offered by investigators to explain
      penicillin treatment failures in GAS tonsillopharyngitis, but the evidence base
      to support the proposed explanations is generally weak by current standards.
      Further research is needed to better understand the mechanism(s) of penicillin
      treatment failure in GAS tonsillopharyngitis.

PMID- 18036410
TI  - Bell's palsy and pregnancy.
AB  - OBJECTIVE: To describe the epidemiology, pathophysiology, presentation,
      treatment, and prognosis of Bell's palsy (BP) in pregnancy. RESULTS: The
      incidence of BP in pregnant women is not significantly greater than expected
      compared to all women of childbearing age. There is a high incidence of cases in
      the third trimester and corresponding low incidence during early pregnancy.
      CONCLUSION: There is no conclusive evidence that the etiology of BP in pregnancy
      is different than in nonpregnant patients. Altered susceptibility to herpes
      simplex viral reactivation during pregnancy is the most likely explanation for
      concentration of cases in the third trimester. Outcome may be poorer in pregnant
      patients, though historically, treatment is often withheld from these patients.
      SIGNIFICANCE: Management of BP in pregnancy can mirror that of nonpregnant
      individuals with the exception of first-trimester cases.

PMID- 18036411
TI  - The use of autogenous costal cartilage graft in septorhinoplasty.
AB  - INTRODUCTION: Reconstructive septorhinoplasty in complex nasal deformities often
      requires harvesting a large amount of tissue for grafting. Autogenous septal
      cartilage has generally been considered the gold standard grafting material. The
      aim of this paper was to report our experience with the use of costal cartilage
      grafts in cases with significant structural deformities and insufficient septal
      cartilage. DESIGN: Retrospective chart review. PATIENTS: Between 1998 and 2006,
      37 patients underwent septorhinoplasty using costal cartilage as the primary
      source for grafting. Twenty-two men and 14 women with a median age of 42 were
      enrolled in the study. Patient demographics, indications for surgery, and
      immediate and late complications were reviewed. The follow-up range was 3 to 72
      months. CONCLUSIONS: Autogenous costal cartilage graft is a viable option in
      reconstructive septorhinoplasty. We advocate the use of this graft in
      septorhinoplasty cases requiring a large volume of tissue and insufficient septal
      cartilage.

PMID- 18036412
TI  - Quantitative and qualitative dermal change with microfat grafting of facial
      scars.
AB  - OBJECTIVE: To evaluate changes in dermal characteristics with subdermal fat
      grafting of cutaneous scars. DESIGN: Prospective cohort. METHODS: Fourteen
      patients with various scar types were treated with subdermal fat grafting over 30
      months. Dermal elasticity, vascularity, pigmentation, patient perception and
      satisfaction, and observer assessment of scar characteristics were evaluated
      preoperatively and 1 year after treatment with validated objective and subjective
      measures. RESULTS: Significant improvements were observed in dermal elasticity,
      patient and observer perception of scar thickness, patient perception of
      stiffness, and observer perception of relief and pliability (P < 0.05). A trend
      toward significance was seen in observer assessment of height as evaluated by the
      Vancouver Scar Scale (P < 0.1). No significant differences were seen in
      quantitatively and qualitatively measured vascularity and pigmentation (P > 0.1).
      No significant difference in pain, pruritus, and irregularity were reported (P >
      0.1). CONCLUSION: Although fat grafting represents a subdermal process, it
      appears to improve certain quantitative and qualitative dermal characteristics.
      Fat grafting does not appear to affect skin color, vascularity, or patient
      symptoms.

PMID- 18036413
TI  - Long-term improvements in quality-of-life after surgical therapy for pediatric
      sinonasal disease.
AB  - OBJECTIVE: To study long-term changes in quality-of-life (QOL) in children after
      surgery for chronic sinonasal disease. DESIGN: Prospective, nonrandomized.
      METHODS: Caregivers completed the SN-5 QOL instrument before surgery. Children
      underwent either adenoidectomy or endoscopic sinus surgery (ESS). Caregivers then
      completed a survey <6 months (short-term) and between six and 24 months after
      surgery (long-term). Scores were compared using a paired t test. RESULTS: Twenty
      two children were enrolled (mean age, 5.7 years). The majority (59%) of children
      underwent ESS. The mean preoperative total score was 25.6. Postoperatively, the
      mean total score was 11.7 at short-term (P < 0.0001) and 11.5 at long-term follow
      up (P < 0.0001). Short- and long-term postoperative scores for all domains were
      significantly different from preoperative scores. In the long-term scores, the
      domain with the greatest change was "emotional distress" (SRM 1.9) and with the
      smallest change was "allergy symptoms" (SRM 1.0). There were no significant
      differences between children who underwent adenoidectomy compared with ESS.
      CONCLUSIONS: After adenoidectomy or ESS, caregivers observe a long-term
      improvement in QOL of children with sinonasal disease.

PMID- 18036414
TI  - Prevalence and ethnicity of sleep-disordered breathing and obesity in children.
AB  - OBJECTIVES: To compare the prevalence of obesity in children with sleep
      disordered breathing (SDB) who undergo adenotonsillectomy to that in the general
      pediatric population. DESIGN: Cross-sectional controlled study. METHODS: A body
      mass-index (BMI-for-age) percentile was determined for children with SDB and for
      matched controls from a general pediatric clinic. Children who were obese (>85th
      %) were analyzed. Groups were compared using a t test or chi(2) analysis. Risk
      factors were estimated with logistic regression. RESULTS: The study population
      included 299 children, of whom 170 (56.9%) had SDB. Compared with controls, more
      children with SDB were obese (46% vs 33%, P = 0.029) or underweight (8% vs 3%, P
      = 0.110), and fewer children with SDB were healthy weight (46% vs 64%, P =
      0.002). Among African American children, those who were obese were more likely to
      have SDB (OR, 2.22, P < 0.01). CONCLUSIONS: Children with SDB who undergo
      adenotonsillectomy are more likely to be obese than children seen in a general
      pediatric clinic. African American children who are obese are more likely to have
      SDB.

PMID- 18036415
TI  - High energy single session radiofrequency tongue treatment in obstructive sleep
      apnea surgery.
AB  - OBJECTIVE: To evaluate the safety and outcomes of a high-energy single session
      treatment as an alternative to a cumulative energy multiple staged approach when
      using temperature-controlled radiofrequency tissue ablation (TCRFTA) for tongue
      base obstruction in sleep apnea surgery. STUDY DESIGN AND METHODS: Retrospective
      study of 176 consecutive Fujita II (tongue and palate level obstruction) patients
      undergoing single session palate, tonsil, and nasal surgery, and concurrent
      tongue base TCRFTA by the application of 10,500 J of energy. RESULTS: Median
      follow-up was 156.5 days. There were no serious complications. There were five
      (2.8%) superficial tongue ulcers, and three (1.7%) persistent taste disturbances
      after treatment; 174 patients were on sustainable oral intake and adequate oral
      pain control within 24 hours of surgery; 98 had comparable post operative sleep
      studies. Apnea-hypopnea indexes decreased from 35.3 +/- 23.9 to 22.6 +/- 21.5 (P
      < 0.0001). Epworth Sleepiness Scale scores improved from 11.2 +/- 4.9 to 5.9 +/-
      4.6 (P < 0.000001). CONCLUSION: High energy single session tongue base TCRFTA is
      a safe procedure with low morbidity.

PMID- 18036416
TI  - Evaluation of the inferior and superior laryngeal nerve stumps for perineural
      spread in laryngeal cancer.
AB  - OBJECTIVE: Perineural spread (PNS) is an important risk factor for locoregional
      failure and is correlated with reduced survival rates in squamous cell carcinoma
      of the larynx. PNS may extend proximally and/or distally in the nerve sheath by
      leaving uninvolved nerve segments. This method of extension may preclude
      obtaining tumor-free surgical margins, which may be responsible for recurrent
      disease. The purpose of this study is to investigate the presence or absence of
      PNS in extralaryngeal superior and inferior laryngeal nerves in patients who
      underwent total laryngectomy for squamous cell carcinoma of the larynx. METHODS:
      Extralaryngeal segments of superior and inferior laryngeal nerves were resected
      bilaterally during 15 consecutive laryngectomies. Laryngectomy specimens and the
      harvested proximal nerve segments were histopathologically examined for the
      presence or absence of PNS. RESULTS: Ten of 15 laryngectomy specimens showed PNS;
      however, none of the extralaryngeal superior or inferior laryngeal nerve segments
      revealed perineural involvement. CONCLUSION: Extralaryngeal extension of PNS is
      highly unlikely in squamous cell carcinoma of the larynx.

PMID- 18036417
TI  - Management outcomes following lateral temporal bone resection for ear and
      temporal bone malignancies.
AB  - OBJECTIVE: To evaluate clinical outcomes following lateral temporal bone
      resection (LTBR) for management of malignancies involving the ear or temporal
      bone. SUBJECTS AND METHODS: A retrospective medical record review was performed
      on patients receiving LTBR for management of malignancies involving the ear or
      temporal bone between 1990 and 2007. RESULTS: In this group of 35 patients, the
      mean age was 62.7 years, with tumor histopathologies including squamous cell
      carcinoma (SCC, 20), basal cell carcinoma (BCC, 7), adenoid cystic carcinoma
      (ACC, 7), and adenocarcinoma (1). The 5-year overall survival (OS), disease
      specific survival (DSS), and disease-free survival (DFS) were 77%, 79%, and 52%,
      respectively. Complete resection resulted in improved OS, DSS, and DFS (P < 0.004
      for each) and reduced local recurrence (P < 0.001). CONCLUSIONS: In patients with
      carcinomas of the ear and temporal bone, upfront excision including LTBR is an
      effective management when combined with postoperative radiation therapy. Complete
      removal of all disease may improve survival and decrease recurrence.

PMID- 18036418
TI  - Extending the traditional resection limits of squamous cell carcinoma of the
      anterior skull base.
AB  - OBJECTIVES: Preliminary report to evaluate the efficacy of resection of squamous
      cell carcinomas that demonstrate intracranial invasion. METHODS: A retrospective
      review of all cases of extracranial squamous cell carcinomas that extend
      intracranially treated by a single surgeon. RESULTS: A total of 21 cases were
      reviewed. In 6 cases, there was noted to be overt brain invasion. Complete
      resection of the intracranial disease was achieved in each of the remaining 15
      cases. There were no instances of CSF leak, meningitis, brain abscess, stroke, or
      other intracranial complication noted either acutely or secondarily. In follow
      ups that ranged from 10 months (single patient died of disease at 10 months) to 6
      years (average, 3.8 years), there were no instances of intracranial recurrence.
      There was a disease-free control rate of 67.7% at an average follow-up of 4.1
      years. CONCLUSIONS: Extending the resection of squamous cell carcinoma into the
      intracranial vault judiciously as outlined appears to be associated with
      acceptable outcomes in the treatment of advanced squamous cell carcinoma of the
      skull base.

PMID- 18036419
TI  - Mid-temporal pericranial and inferiorly based periosteal flaps in mastoid
      obliteration.
AB  - OBJECTIVE: To study the outcome of mastoid obliterations where mid-temporal
      pericranial flap and inferiorly based periosteal flap were used. STUDY DESIGN: A
      prospective longitudinal study with a minimum follow-up of 1 year. SUBJECTS AND
      METHODS: Between 2000 and 2005, 102 mastoid obliterations were performed on 96
      patients, the majority having hydroxyapatite granules as fillers. Of these, 31
      were primary obliterations and 71 were secondary obliterations. Thirty were on
      children under 16. RESULTS: Using Kaplan-Meier analysis, the percentage of ears
      that were free of residual cholesteatoma at 5 years was 91% (95% CI: 83.1%,
      100.0%). There was no recurrent cholesteatoma. Cut-off analysis was used to study
      other parameters at 5 years. The 5-year otorrhea rate was zero, and 96% of the
      cavities became completely epithelialized. Twenty out of 24 ears were water
      resistant, and 50% had air-bone gaps of 20 dB or better. CONCLUSION: The outcome
      of this technique compares favorably to other reports.

PMID- 18036420
TI  - Improvements to staged canal wall up tympanoplasty for middle ear cholesteatoma.
AB  - OBJECTIVE: To describe our improvements to staged canal wall up tympanoplasty
      with mastoidectomy (SCUT) for middle ear cholesteatoma, and to show more
      successful outcomes of the surgery compared with our data previously reported.
      STUDY DESIGN: Retrospective study in a tertiary referral hospital. SETTING: 78
      ears of 76 patients with extensive cholesteatoma were operated on using the
      improved SCUT between July 1998 and December 2006. Improved SCUT included new
      techniques such as scutum plasty and mastoid cortex plasty performed in a staged
      manner. RESULTS: Only 2 ears showed retraction pocket formation (7.7%) without
      recurrence in 26 ears followed for more than 5 years. In 48 followed for more
      than 3 years, frequency of postoperative retraction pocket formation (5/48;
      10.4%) was significantly lower compared to our previous results (41/134; 30.6%, P
      < 0.01). CONCLUSION: Our improvements to SCUT contributed to the decreasing of
      frequency of postoperative retraction pocket that may lead to cholesteatoma
      recurrence, although a longer follow-up study is required.

PMID- 18036422
TI  - Histological and immunological features of non-eosinophilic nasal polyps.
AB  - OBJECTIVE: The aim of this study was to investigate the histoimmunological
      features of non-eosinophilic nasal polyps (NPs). METHODS: Thirty patients with
      chronic rhinosinusitis and NPs were included in this study. NPs were grouped into
      eosinophilic and non-eosinophilic types according to the amount of eosinophils in
      the NPs. The amount of serum total IgE and peripheral blood eosinophils were
      measured. Basement membrane (BM) thickness was measured, along with the
      expression of chemokine receptor 5 (CCR5) and chemokine receptor 3 (CCR3) in NP
      lymphocytes. RESULTS: Non-eosinophilic NPs comprised 66.7% of the total NPs
      included in this study. The amount of eosinophils in NPs was related to
      eosinophilia of the peripheral blood, but not to elevated serum IgE. BM was
      significantly thinner in non-eosinophilic than in eosinophilic NPs. Lymphocytes
      expressing CCR5 or CCR3 were less frequently found in non-eosinophilic than in
      eosinophilic NPs. CONCLUSION: Histoimmunological characteristics of non
      eosinophilic NPs differ from those of eosinophilic NPs; non-eosinophilic NPs may
      be featured by thinner BM and fewer CCR5- and CCR3-positive lymphocytes.

PMID- 18036421
TI  - An assessment of the onset and duration of action of olopatadine nasal spray.
AB  - OBJECTIVE: Seasonal allergic rhinitis (SAR) is a highly prevalent disease. This
      study was conducted to evaluate the onset and duration of action of three
      concentrations of olopatadine nasal spray. METHODS: This was a randomized, double
      blind, single-dose, placebo-controlled study, conducted in an environmental
      exposure chamber in patients with SAR. A total of 320 patients were exposed to
      ragweed allergen in the chamber and randomized to olopatadine nasal spray 0.2%,
      0.4%, 0.6%, or placebo nasal spray. Symptoms (sneezing, runny, itchy, and stuffy
      nose) were self-assessed during a 12-hour study period. RESULTS: All
      concentrations of olopatadine nasal spray provided clinically meaningful
      reductions in total nasal symptom scores at 30 minutes compared to the placebo.
      Olopatadine nasal spray 0.6% was significantly more effective (P < 0.05) than
      placebo nasal spray at all time-points starting at 90 minutes post-dose and
      continuing over 12 hours. CONCLUSIONS: Olopatadine nasal spray 0.6% demonstrated
      a fast onset of action and maintained an effect for at least 12 hours after
      dosing.

PMID- 18036423
TI  - Clinical experience with angiotensin-converting enzyme inhibitor-induced
      angioedema.
AB  - OBJECTIVES: To understand the presentation and clinical course of angiotensin
      converting enzyme (ACE) inhibitor-induced angioedema and to determine management
      factors associated with progression to airway compromise. STUDY DESIGN AND
      SETTING: Retrospective chart review of patients taking ACE inhibitors who
      presented to the emergency department with angioedema between December 1999 and
      July 2004 (n = 228). Clinical presentation, treatment, and clinical course were
      analyzed. RESULTS: The oral cavity was the most common location of upper-airway
      angioedema. Twenty-two (10%) patients required intubation, and all were intubated
      within 12 hours of presentation. Of the patients who required intubation, those
      who were started on an H(1)-blocker were extubated earlier than those not on an
      H(1)-blocker (P = 0.05). CONCLUSION: The locations of swelling and drooling on
      admission are predictive of the need for intubation. Other aspects of
      presentation, treatment, and disposition can help in management decisions for
      this potentially fatal condition. SIGNIFICANCE: This is the largest series to
      date of ACE inhibitor-related angioedema that challenges theories on the etiology
      and treatment of this condition.

PMID- 18036424
TI  - Dosing of proton pump inhibitors is suboptimal among otolaryngologists treating
      reflux-induced upper-respiratory disease.
AB  - OBJECTIVE: To evaluate the practice of otolaryngologists treating reflux-induced
      upper-respiratory disease in a nationwide survey. STUDY DESIGN: Survey study
      using an anonymous questionnaire containing clinical vignettes. SUBJECTS AND
      METHODS: The survey was mailed to all 6,899 board-certified fellow members in
      practice in the American Academy of Otolaryngology-Head and Neck Surgery residing
      in the United States. RESULTS: One thousand seven hundred twenty questionnaires
      were returned. Respondents empirically treated reflux-induced upper-respiratory
      disease with proton pump inhibitors once daily and twice daily 63% and 31%,
      respectively. Fifteen percent did not instruct their patients on how to take the
      proton pump inhibitors. Of those who instructed their patients, 22% advised
      dosing before breakfast, 32% before breakfast and again before dinner, and 46%
      recommended other timings. When prescribing twice-per-day dosing, 64% responded
      to give before breakfast and dinner and 28% responded before breakfast and at
      bedtime. CONCLUSION: Suboptimal dosing of proton pump inhibitors is prevalent
      among otolaryngologists treating reflux-induced upper-respiratory disease.

PMID- 18036425
TI  - Acute rise in methicillin-resistant Staphylococcus aureus infections in a coastal
      community.
AB  - OBJECTIVE: Describe the incidence of head and neck community-acquired methicillin
      resistant Staphylococcus aureus (CA-MRSA) infections over a 5-year period at a
      coastal tertiary medical center. STUDY DESIGN: Retrospective chart review.
      SUBJECTS AND METHODS: All patients presenting to the otolaryngology service with
      cultures taken from head and neck infections between 1999 and 2004 were eligible
      for inclusion. Statistical analysis was used to determine significance of the
      changing incidence of isolated organisms over the study period. RESULTS: CA-MRSA
      infections rose from 21% to 64% over the 5-year period. The increasing trend in
      CA-MRSA infections reached statistical significance from 2003 to 2004. All CA
      MRSA isolates were resistant to cefazolin and penicillin, but most were sensitive
      to clindamycin. CONCLUSIONS: Our data demonstrates a striking increase in the
      incidence of CA-MRSA. We have tailored our treatment of cutaneous head and neck
      infections to include empiric treatment for CA-MRSA using clindamycin. Awareness
      and monitoring of this trend will be important for all practitioners involved in
      the care of these patients.

PMID- 18036426
TI  - Early experience with minimally invasive esophagectomy in head and neck surgical
      patients.
AB  - BACKGROUND: Minimally invasive esophagectomy (MIE) via thoracoscopy and
      laparoscopy have reduced the morbidity and mortality of total esophagectomy at
      experienced centers. MIE has not been evaluated in combination with major head
      and neck surgery, or in the otolaryngology literature. METHODS: Case series of 11
      consecutive patients undergoing either open or MIE with an ablative neck
      procedure. RESULTS: Comparing 4 MIEs and 7 open operations, similar operative
      time, blood loss, and ICU and hospital length of stay were observed. There was
      one mortality in the open group. A 100% rate of major complications was observed
      in the MIE group. CONCLUSION: Our multidisciplinary team was unable to achieve
      improved outcomes in a series of head and neck surgical patients undergoing MIE.
      This result may represent an early stage of the learning curve for MIE, but may
      also be attributed to the escalated surgical requirements of head and neck
      patients.

PMID- 18036427
TI  - Coenzyme Q10 does not protect cochlear hair cells from death in the ischemic
      organotypic culture.
AB  - OBJECTIVE: To evaluate in vitro the effect of coenzyme Q10 (CoQ(10)) on ischemia
      induced hair cell death. STUDY DESIGN: Organotypic cochlear cultures of newborn
      rats were subjected to ischemia with and without CoQ(10). RESULTS: Addition of
      CoQ(10) has not prevented HC loss. CONCLUSION: CoQ(10) seems to protect against
      only certain modes of cell death.

PMID- 18036428
TI  - Estimate of radiation dose to the lens in balloon sinuplasty.
AB  - OBJECTIVES: To estimate radiation dose to the lens during fluoroscopy-assisted
      balloon dilation of sinus ostia and to estimate the length of fluoroscopy time
      that will be tolerated. METHODS: Radiation dose to the lens per unit fluoroscopy
      time was extrapolated from published data in fluoroscopically-guided balloon
      dacrocystoplasty. RESULTS: Mean exposure varies from 0.041 (right eye) to 0.284
      (left eye) mGy/sec (P = 0.037) because the left eye is closer to the radiation
      source during the lateral projection. Threshold for lenticular opacity has been
      estimated as 500 mGy, which would be attained in the left eye after approximately
      29 minutes of fluoroscopy. CONCLUSIONS: The lens may tolerate <30 minutes of
      fluoroscopy during balloon sinuplasty. The left eye receives a potentially
      greater radiation dose because of its proximity to the source in the lateral
      projection. Dedicated studies are indicated to specifically examine this issue
      during balloon sinuplasty.

PMID- 18036429
TI  - Effects of flexible fiberoptic endoscopy on pharyngeal swallow physiology.
AB  - OBJECTIVE: The purpose of this study was to determine if the presence of a
      flexible fiberoptic endoscope in the pharynx affects swallow physiology. STUDY
      DESIGN: This was a prospective cohort study. SUBJECTS AND METHODS: Fourteen
      individuals with normal swallow function, 23 to 83 years of age, completed a
      videofluoroscopic swallow study with and without a 3.5 mm flexible fiberoptic
      endoscope maintained in the "high" position, ie, below the velopharyngeal port
      and above the epiglottis. Each study was analyzed for three swallow duration
      measures, number of swallows necessary to clear the bolus, and penetration
      aspiration scale scores. RESULTS: No significant (P > 0.05) main effects for
      condition were found for swallow duration, penetration-aspiration scale scores
      and number of swallows to clear the bolus. CONCLUSION: The presence of a flexible
      fiberoptic endoscope in the pharynx during swallowing did not significantly
      affect pharyngeal swallow physiology in the patients studied, but we cannot
      exclude a false-negative conclusion because of low statistical power.

PMID- 18036430
TI  - Acquired nasopharyngeal stenosis: surgical treatment for this unusual
      complication after chemoradiation for nasopharyngeal carcinoma.

PMID- 18036431
TI  - Doxycycline sclerotherapy as the primary treatment for head and neck lymphatic
      malformations.

PMID- 18036432
TI  - Aspiration of a capsule endoscope and description of a unique retrieval
      technique.

PMID- 18036433
TI  - Post-transplant actinomycosis of the posterior glottis involving both vocal
      processes.

PMID- 18036434
TI  - Bilateral pneumolabyrinth diagnostic for otic capsule fractures without high
      resolution imaging.

PMID- 18036435
TI  - Clear cell chondrosarcoma in the nasal septum.

PMID- 18036436
TI  - Tuberculosis of the temporomandibular joint and parotid secondary to tuberculous
      otitis media.

PMID- 18036437
TI  - Lipofibroma of the neck in children: an unusual diagnosis with special surgical
      implications.

PMID- 18036438
TI  - Neck mass with epithelial papillae: a diagnostic pitfall in aspiration cytology.

PMID- 18036439
TI  - Entire infrasellar craniopharyngioma simulating clival chordoma.

PMID- 18036440
TI  - A biased LPR meta-analysis.

PMID- 18036442
TI  - Re: Comorbidities in head and neck cancer: agreement between self-report and
      chart review.

PMID- 18036444
TI  - Anti-myeloma activity of endogenous and adoptively transferred activated natural
      killer cells in experimental multiple myeloma model.
AB  - OBJECTIVE: Despite advances in autologous stem cell transplantation and
      chemotherapy, multiple myeloma (MM) remains an incurable disease. Due to the role
      of natural killer (NK) cells in host resistance against several tumors, it is of
      interest to explore the anti-MM activity of NK cells. For this reason, we aimed
      to determine if NK cells provide anti-MM activity following interleukin-2 (IL-2)
      administration, and if ex vivo activated and intravenously administered NK cells
      prolong survival in MM-bearing C57BL/KaLwRij mice. METHODS: The anti-MM effect of
      IL-2 was tested by intraperitoneal injection into the 5T33MM-inoculated mice.
      Subsequently, in vivo effector cell depletions were performed by administration
      of anti-NK1.1 or anti-CD8 monoclonal antibodies. Finally, magnetically separated
      and activated NK cells from splenocytes of C57BL/KaLwRij mice were adoptively
      transferred to tumor-bearing mice in conjunction with IL-2 treatment. RESULTS: IL
      2 administration into MM-bearing mice significantly prolonged their survival.
      This effect was diminished by in vivo depletion of NK cells. Adoptive transfer of
      activated NK cells showed a significant in vivo anti-MM effect that was dependent
      on cell dose. Biodistribution of the marked adoptively transferred NK cells
      correlated with MM cells' homing sites. CONCLUSION: These data suggest that
      activated NK cells have a promising potential in adoptive immunotherapy for MM.

PMID- 18036445
TI  - Evaluation and management of the cardiac amyloidosis.
AB  - Cardiac amyloidosis describes clinically significant involvement of the heart by
      amyloid deposition, which may or may not be associated with involvement of other
      organs. The purpose of this review is to summarize the current state of evidence
      for the effective evaluation and management of cardiac amyloidosis. Acquired
      systemic amyloidosis occurs in more than 10 per million person-years in the U.S.
      population. Although no single noninvasive test or abnormality is pathognomonic
      of cardiac amyloid, case-control studies indicate that echocardiographic evidence
      of left ventricular wall thickening, biatrial enlargement, and increased
      echogenicity in conjunction with reduced electrocardiographic voltages is
      strongly suggestive of cardiac amyloidosis. Furthermore, newer echocardiographic
      techniques such as strain and strain rate imaging can demonstrate impairment in
      longitudinal function before ejection fraction becomes abnormal. Recent
      observational studies also suggest that cardiovascular magnetic resonance imaging
      yields characteristic findings in amyloidosis, offering promise for the early
      detection of cardiac involvement, and the presence of detectable cardiac troponin
      and elevated B-type natriuretic peptide in serum of affected patients portends an
      adverse prognosis. Management strategies for cardiac amyloid are largely based on
      nonrandomized single-center studies. One of the few published randomized studies
      shows the superiority of oral prednisolone and melphalan compared with colchicine
      in systemic AL amyloidosis. Intermediate-dose infusional chemotherapy regimes
      (such as vincristine, adriamycin, and dexamethasone) and high-dose chemotherapy
      with peripheral stem cell rescue have been used widely, but treatment-related
      mortality remains substantial with chemotherapy. Recent studies also indicate
      promising strategies to stabilize the native structures of amyloidogenic
      proteins; inhibit fibril formation; and disrupt established deposits using
      antibodies, synthetic peptides, and small-molecule drugs.

PMID- 18036446
TI  - Gender-specific outcomes after sirolimus-eluting stent implantation.
AB  - OBJECTIVES: We examined the impact of gender on outcomes of patients undergoing
      percutaneous coronary intervention using sirolimus-eluting stents (SES).
      BACKGROUND: Although gender-specific differences in outcome after implantation of
      bare-metal stents (BMS) have been described, there are no data assessing outcomes
      of women treated with SES. METHODS: We performed a patient-level pooled analysis
      from 4 randomized SES versus BMS trials (RAVEL [Randomized Comparison of a
      Sirolimus-Eluting Stent with a Standard Stent for Coronary Revascularization],
      SIRIUS [SIRolImUS-coated Bx Velocity balloon expandable stent in the treatment of
      patients with de novo coronary artery lesions], E-SIRIUS [Sirolimus-eluting
      stents for treatment of patients with long atherosclerotic lesions in small
      coronary arteries], and C-SIRIUS [Canadian study of the sirolimus-eluting stent
      in the treatment of patients with long de novo lesions in small native coronary
      arteries]) and analyzed outcomes as a function of gender. RESULTS: Of 1,748
      patients, 1,251 were men and 497 were women. A total of 878 patients were
      randomized to SES (629 men and 249 women), and 870 patients were randomized to
      BMS (622 men and 248 women). Compared with men, women were older and more
      frequently had diabetes mellitus, hypertension, and congestive heart failure.
      Although overall clinical outcomes were similar in both genders, treatment with
      SES was associated with significant (p < 0.0001) reductions in rates of in
      segment binary restenosis both in women (6.3% vs. 43.8%) and in men (6.4% vs.
      35.6%), resulting in a significant reduction in 1-year major adverse cardiac
      events, driven by a lower incidence of target lesion revascularization/target
      vessel revascularization in both genders. By multivariable analysis, female
      gender was not an independent predictor of in-segment binary restenosis or
      clinical outcomes regardless of stent type. CONCLUSIONS: In this analysis,
      despite less favorable baseline clinical and angiographic features in women
      compared with men, the angiographic and clinical benefits of SES were independent
      of gender.

PMID- 18036447
TI  - Serial measurement of monocyte chemoattractant protein-1 after acute coronary
      syndromes: results from the A to Z trial.
AB  - OBJECTIVES: This study sought to determine whether the novel biomarker monocyte
      chemoattractant protein (MCP)-1 adds prognostic value to standard risk assessment
      tools and biomarkers after acute coronary syndromes (ACS). BACKGROUND: Monocyte
      chemoattractant protein-1 is a chemokine recruiting signal for monocytes that may
      function as both a mediator and biomarker of ACS. METHODS: Monocyte
      chemoattractant protein-1 was measured at baseline (n = 4,244), 4 months (n =
      3,603), and 12 months (n = 2,950), and correlated with clinical events in the Z
      phase of the A to Z (Aggrastat to Zocor) trial, which compared early intensive
      versus delayed and less intensive statin therapy after ACS. RESULTS: Rates of
      death and the composite end points of death or myocardial infarction (MI); death,
      MI, or heart failure; and cardiovascular death, MI, readmission for ACS, or
      stroke increased across baseline quartiles of MCP-1 and among patients with MCP-1
      greater than versus less than or equal to the pre-specified threshold of 238
      pg/ml (p < 0.01 for each). After adjustment for standard risk predictors and
      levels of C-reactive protein and B-type natriuretic peptide, MCP-1 >238 pg/ml
      remained independently associated with mortality (hazard ratio 2.16; 95%
      confidence interval 1.54 to 3.02) and with each composite end point, and
      increased the C-statistic of the fully adjusted mortality model from 0.76 to 0.78
      (p < 0.0001). A value of MCP-1 >238 pg/ml at the 4-month follow-up visit was also
      independently associated with mortality after 4 months (hazard ratio 1.76; 95%
      confidence interval 1.12 to 2.76). Elevated MCP-1 levels did not identify
      patients who derived incremental benefit from intensive statin therapy.
      CONCLUSIONS: Monocyte chemoattractant protein-1 provides independent prognostic
      value in the acute and chronic phases after ACS and merits further evaluation as
      a prognostic marker and potential therapeutic target.

PMID- 18036448
TI  - The prognostic value of monocyte chemoattractant protein-1/CCL2 in acute coronary
      syndromes.

PMID- 18036449
TI  - Coronary heart disease mortality among young adults in the U.S. from 1980 through
      2002: concealed leveling of mortality rates.
AB  - OBJECTIVES: The objective of our study was to examine age-specific mortality
      rates from coronary heart disease (CHD), particularly those among younger adults.
      BACKGROUND: Trends for obesity, diabetes, blood pressure, and metabolic syndrome
      among young adults raise concerns about the mortality rates from CHD in this
      group. METHODS: We used mortality data from 1980 to 2002 to calculate age
      specific mortality rates from CHD for U.S. adults age > or =35 years. RESULTS:
      Overall, the age-adjusted mortality rate decreased by 52% in men and 49% in
      women. Among women age 35 to 54 years, the estimated annual percentage change
      (EAPC) in mortality was -5.4% (95% confidence interval [CI] -5.8 to -4.9) from
      1980 until 1989, -1.2% (95% CI -1.6 to -0.8) from 1989 until 2000, and 1.5% (95%
      CI -3.4 to 6.6) from 2000 until 2002. Among men age 35 to 54 years, the EAPC in
      mortality was -6.2% (95% CI -6.4 to -5.9) from 1980 until 1989, -2.3% (95% CI 
      2.6 to -2.1) from 1989 until 2000, and -0.5% (95% CI -3.7 to 2.9) from 2000 until
      2002. Among women and men age > or =55 years, the estimated annual percentage
      decrease in mortality from CHD accelerated in more recent years compared with
      earlier periods. CONCLUSIONS: The mortality rates for CHD among younger adults
      may serve as a sentinel event. Unfavorable trends in several risk factors for CHD
      provide a likely explanation for the observed mortality rates.

PMID- 18036450
TI  - Time to end the mixed--and often incorrect--messages about prevention and
      treatment of atherosclerotic cardiovascular disease.

PMID- 18036451
TI  - Long-term use of sildenafil in the therapeutic management of heart failure.
AB  - OBJECTIVES: This study sought to test the functional exercise capacity and
      endothelial function in a cohort of chronic heart failure (CHF) patients treated
      with chronic type 5 phosphodiesterase (PDE5) inhibitor. BACKGROUND: In CHF,
      endothelial dysfunction is involved in muscle underperfusion, ergoreflex
      oversignaling, and exercise ventilation inefficiency. Inhibition of PDE5 by
      improving endothelial dysfunction might be beneficial. METHODS: Stable CHF
      patients were randomly assigned to placebo (23 patients) or sildenafil at the
      dose of 50 mg twice per day (23 patients) in addition to their current drug
      treatment for 6 months, with assessments (at 3 and 6 months) of endothelial
      function by brachial artery flow-mediated dilatation (FMD), cardiopulmonary
      exercise testing, and ergoreflex response. RESULTS: In the sildenafil group only,
      at 3 and 6 months we observed reduction of systolic pulmonary artery pressure
      (from 33.7 to 25.2 mm Hg and 23.9 mm Hg), ergoreflex effect on ventilation (from
      6.9 to 2.3 l x min(-1) and 1.9 l x min(-1)), ventilation to CO2 production slope
      (V(E)/VCO2, from 35.5 to 32.1 and 29.8), and breathlessness (score) (from 23.6 to
      16.6 and 17.2), and an increase of FMD (from 8.5% to 13.4% and 14.2%), peak VO2
      (from 14.8 to 18.5 ml x min(-1) x kg(-1) and 18.7 ml x min(-1) x kg(-1)), and
      ratio of VO2 to work rate changes (from 7.7 to 9.3 and 10.1). All changes were
      significant at p < 0.01. In the sildenafil group, a significant correlation was
      found at 3 and 6 months between changes in FMD and those in ergoreflex. Changes
      in ergoreflex correlated with those in peak VO2 and V(E)/VCO2 slope. No adverse
      effects were noted except for flushing in 3 patients. CONCLUSIONS: In CHF,
      improvement in exercise ventilation and aerobic efficiency with sildenafil is
      sustained and is significantly related with an endothelium-mediated attenuation
      of exercising muscle oversignaling. Chronic sildenafil seems to be a remedy based
      on CHF pathophysiology and devoid of remarkable adverse effects.

PMID- 18036452
TI  - Type 5 phosphodiesterase inhibition in heart failure: the next step.

PMID- 18036453
TI  - The cardioprotective effects of the angiotensin-converting enzyme inhibitor
      perindopril in patients with stable coronary artery disease are not modified by
      mild to moderate renal insufficiency: insights from the EUROPA trial.
AB  - OBJECTIVES: This study sought to examine whether the cardioprotective effects of
      angiotensin-converting enzyme (ACE) inhibitor therapy by perindopril are modified
      by renal function in patients with stable coronary artery disease. BACKGROUND: A
      recent study reported that an impaired renal function identified a subgroup of
      patients with stable coronary artery disease more likely to benefit from ACE
      inhibition therapy. In light of the growing interest in tailored therapy for
      targeting medications to specific subgroups, remarks on the consistency of the
      treatment effect by ACE inhibitors are highly important. METHODS: The present
      study involved 12,056 patients with stable coronary artery disease without heart
      failure randomized to perindopril or placebo. Estimated glomerular filtration
      rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal
      Disease equation. Cox regression analysis was used to estimate multivariable
      adjusted hazard ratios. RESULTS: The mean eGFR was 76.2 (+/-18.1) ml/min/1.73 m2.
      During follow-up, the primary end point (cardiovascular death, nonfatal
      myocardial infarction, or resuscitated cardiac arrest) occurred in 454 of 5,761
      patients (7.9%) with eGFR > or =75 and in 631 of 6,295 patients (10.0%) with eGFR
      <75. Treatment benefits of perindopril were apparent in both patient groups
      either with eGFR > or =75 (hazard ratio 0.77; 95% confidence interval 0.64 to
      0.93) or eGFR <75 (hazard ratio 0.84; 95% confidence interval 0.72 to 0.98). We
      observed no significant interaction between renal function and treatment benefit
      (p = 0.47). Using different cutoff points of eGFR at the level of 60 or 90
      resulted in similar trends. CONCLUSIONS: The treatment benefit of perindopril is
      consistent and not modified by mild to moderate renal insufficiency.

PMID- 18036454
TI  - Incidence of stroke in paroxysmal versus sustained atrial fibrillation in
      patients taking oral anticoagulation or combined antiplatelet therapy: an ACTIVE
      W Substudy.
AB  - OBJECTIVES: Our goal was to determine the risk of stroke or non-cerebral embolism
      associated with paroxysmal compared with sustained atrial fibrillation (AF).
      BACKGROUND: The risk of stroke and non-cerebral embolism and the efficacy of oral
      anticoagulation (OAC) in paroxysmal AF as compared with sustained AF are not
      precisely known. METHODS: The ACTIVE W (Atrial Fibrillation Clopidogrel Trial
      With Irbesartan for Prevention of Vascular Events) was a trial comparing OAC to
      combined antiplatelet therapy with aspirin and clopidogrel for prevention of
      vascular events in 6,706 AF patients. The incidence of thromboembolic events and
      major bleeds were compared in patients with paroxysmal AF (n = 1,202) and
      persistent or permanent AF (n = 5,495). RESULTS: Patients with paroxysmal AF were
      younger, had a shorter AF history, more hypertension, and less valvular disease,
      heart failure, and diabetes mellitus than patients with sustained AF. At
      baseline, patients with paroxysmal AF had a CHADS2 (cardiac failure,
      hypertension, age, diabetes, stroke [doubled]) risk score of 1.79 +/- 1.03
      compared with 2.04 +/- 1.12 in patients with sustained AF (p < 0.00001). The
      annualized risk of stroke or non-central nervous system (CNS) systemic embolism
      was 2.0 in paroxysmal AF compared with 2.2 in sustained AF (relative risk 0.87,
      95% confidence interval [CI] 0.59 to 1.30, p = 0.496). After adjusting for
      confounding baseline variables, the relative risk was 0.94 (95% CI 0.63 to 1.40,
      p = 0.755). The incidence of stroke and non-CNS embolism was lower for patients
      treated with OAC irrespective of type of AF. There were more bleedings of any
      type in patients receiving clopidogrel plus aspirin, irrespective of the type of
      AF. CONCLUSIONS: Patients with paroxysmal AF treated with aspirin plus
      clopidogrel or OAC have a similar risk for thromboembolic events than patients
      with sustained AF. This risk can be significantly lowered with OAC. (The ACTIVE W
      trial; http://www.clinicaltrials.gov/ct/show/NCT00243178;NCT00243178).

PMID- 18036455
TI  - Noncontact mapping and radiofrequency catheter ablation of fast and
      hemodynamically unstable ventricular tachycardia after surgical repair of
      tetralogy of Fallot.
AB  - OBJECTIVES: The goal of this work was to assess efficacy of radiofrequency (RF)
      ablation of fast ventricular tachycardia (VT) in patients after surgical repair
      of tetralogy of Fallot (TOF) guided by noncontact mapping. BACKGROUND:
      Ventricular tachycardias after repair of TOF are associated with significant
      morbidity and mortality. METHODS: Ten patients after surgical repair of TOF
      underwent electrophysiological study for hemodynamically unstable VT using the
      noncontact mapping system. Dynamic substrate mapping was performed and activation
      was recorded during basic rhythm and induced VT (mean cycle length 269 ms) using
      color-coded isopotential maps and reconstructed unipolar electrograms. RESULTS: A
      total of 13 VTs were induced in the 10 patients. In 11 of 13 VTs, a macro-re
      entrant mechanism was identified; 2 had a focal origin. For macro-re-entrant VT,
      RF current lesion lines were created between areas of residual conduction; in 2
      patients, no RF current was delivered due to high risk of atrioventricular block.
      Focal applications were performed for the focal VTs. Ventricular tachycardia was
      not inducible after RF application in the 8 patients in whom ablation was
      attempted (100%, 80% of all patients). An internal cardioverter-defibrillator had
      already been implanted in 2 patients and was recommended to the rest of the
      group. During follow-up (mean 35.4 months), 6 of 8 patients with a successful
      procedure were still free of VT, and 2 patients had recurrence of VT with a
      different cycle length. CONCLUSIONS: In patients with fast and unstable VT after
      surgical repair of TOF, noncontact mapping helped to identify the tachycardia
      substrate and allowed for effective and safe treatment by RF ablation.

PMID- 18036456
TI  - Waon therapy improves peripheral arterial disease.

PMID- 18036457
TI  - Complex roles of endothelial shear stress in vascular remodeling response.

PMID- 18036459
TI  - Universal definition of myocardial infarction.

PMID- 18036460
TI  - Teen dating violence: an unrecognized health care need.

PMID- 18036461
TI  - Human figure drawings as a measure of children's emotional status: critical
      review for practice.

PMID- 18036463
TI  - Screening for overweight and diabetes in rural Hispanic and Caucasian fifth-grade
      children.
AB  - Fifth-grade children were screened for overweight and diabetes and comparisons
      between Hispanic and Caucasian children in this rural setting are presented.
      Hispanic children had a significantly higher mean Body Mass Index percentile and
      waist circumference than Caucasians but blood glucose differences were not
      significant. Twenty-six percent of all children had slightly elevated glucose
      levels (100-125 mg per dL) and 2% had elevated levels (equal to or greater than
      126 mg per dL) but none of the children were found to have diabetes. There were
      significant positive correlations between random blood glucose, Body Mass Index
      percentile and waist circumference. Researchers concluded that a two-step
      screening process is appropriate.

PMID- 18036464
TI  - Parental holding and positioning to decrease IV distress in young children: a
      randomized controlled trial.
AB  - Young children are generally restrained in supine position for IV starts, a
      position that creates fear but is presumed necessary. This study randomly
      assigned children of ages 9 months to 4 years (N = 118) to being held upright by
      a parent or lying flat on an exam table for their IV procedure. Distress scores
      as rated by the Procedure Behavior Rating Scale were significantly lower in the
      upright positioning group (p = .000); parents were more satisfied with the
      upright position, and the upright position did not significantly alter the number
      of IV attempts needed. The upright position appears to be an effective way to
      decrease IV distress in young children.

PMID- 18036465
TI  - Practice guidelines for music interventions with hospitalized pediatric patients.
AB  - Music therapy is an effective complementary approach that can achieve specific
      therapeutic outcomes in the clinical management of pediatric patients. Growing
      research on music interventions has generated scientific knowledge about how this
      modality benefits patients and has formed the basis for effective protocols that
      can be used in practice. Although it can be challenging to translate research
      based protocols into routine clinical care at the bedside, it is essential that
      music therapy interventions be aligned with evidence-based information and that
      accepted standards be established by the music therapy discipline to achieve the
      greatest benefit. The importance of partnerships between nurses and music
      therapists is emphasized to enhance the success of music-based treatments. This
      discussion synthesizes research findings that can be used to design pediatric
      practice guidelines in the application of music therapy.

PMID- 18036466
TI  - Caring for children with intellectual and developmental disabilities: virtual
      patient instruction improves students' knowledge and comfort level.
AB  - Nurses play a vital role in providing health care to children with developmental
      disability (DD) throughout the United States. Unfortunately, most nurses continue
      to report that they receive little or no clinical education in the area of DDs.
      In response to this need, a core development team consisting of nurse
      practitioners and nursing faculty from three universities, one physician
      assistant faculty, parents of children with DD, and educational specialists
      developed two multimedia (virtual patient) pediatric instructional modules in CD
      ROM format--one involving a child with Down syndrome, and the other involving an
      infant born at 26 weeks' gestation. Participants were required to make clinical
      decisions throughout the cases. The modules on CD were piloted with nursing
      students from three universities. Results of the effectiveness study demonstrated
      significant gains in knowledge and comfort level regarding the care of children
      with DD.

PMID- 18036467
TI  - One-on-one coaching to improve pain assessment and management practices of
      pediatric nurses.
AB  - Pain in children is infrequently assessed and managed by nurses. One-on-one
      coaching based on audit with feedback and the use of opinion leaders have been
      effective in changing professional health care practices. Coaching by an opinion
      leader for changing pediatric nurses' pain practices was tested in a clustered
      randomized trial in six Canadian pediatric hospitals. The rate of pain
      assessments, nurses' knowledge, and nonpharmacological interventions increased in
      the coaching group. However, there were significant site differences that could
      not be attributed to the coaching but to factors inherent in the sites. The
      context in which interventions are implemented will influence the effectiveness
      of individualized interventions.

PMID- 18036468
TI  - Pain management practices for lumbar punctures: are we consistent?
AB  - In most pediatric oncology centers across Canada, it is now standard practice for
      children to be sedated for lumbar punctures (LPs). Although the use of sedation
      for LPs is well established in the pediatric oncology population, its use in
      other hospital units is not well documented. A patient record audit was completed
      to understand the types of pain management strategies used for LPs performed
      throughout a pediatric hospital. Fifty-nine patients aged between 3 days and 17
      years underwent a total of 67 LPs. Pain management strategies varied among the
      different patient service units. Oncology patients were consistently sedated for
      an LP, whereas patients in the emergency department were less likely to be given
      any type of sedation. Recommendations are aimed at providing consistent best
      practice pain management for LPs throughout the hospital.

PMID- 18036469
TI  - Kids in prison.

PMID- 18036470
TI  - From distance toward proximity: fathers lived experience of caring for their
      preterm infants.
AB  - Open interviews with 13 fathers were performed, using a hermeneutic
      phenomenological method, to illuminate their lived experience of caring for their
      preterm infant. Their lived experience was expressed as a process moving from
      initial feelings of distance toward feelings of proximity. The process was
      described as a pendulum that was easily disturbed. Feelings of distance included
      experiences of living beside reality, becoming an outsider, and living with
      worry. Feelings of proximity included experiences of returning to reality,
      becoming a family, and facing the future. Illumination of the father-infant
      interaction adds to the family-centered body of knowledge in neonatal nursing.

PMID- 18036471
TI  - Comparisons of needs, need responses, and need response satisfaction of mothers
      of infants in neonatal intensive care units.
AB  - Providing nursing care to meet the needs of mothers may be unsuccessful because
      most nurses perceive and prioritize maternal needs differently from how mothers
      do. In this study, 140 mothers of infants in each neonatal intensive care unit of
      three hospitals in southern Thailand were interviewed using questionnaires on
      maternal needs, need responses, and need response satisfaction. Significant
      differences in mean total scores and mean subscale scores of needs, need
      responses, and need response satisfaction were found among the three groups of
      mothers. Significant differences in mean differences of total needs, need
      responses, and need response satisfaction were found when comparing mothers in
      each group. The mean rankings of maternal needs, need responses, and need
      response satisfaction were identified. This study supported the idea of
      individualized maternal needs and priorities. In providing effective nursing care
      to meet the needs and satisfaction of mothers, nurses should be concerned with
      the needs of individuals, their responses to those needs, and need response
      satisfaction because the satisfaction of these needs is essential for infant well
      being.

PMID- 18036472
TI  - Pediatric intensive care unit admission tool: a colorful approach.
AB  - This article discusses the development, implementation, and utilization of our
      institution's Pediatric Intensive Care Unit (PICU) Color-Coded Admission Status
      Tool. Rather than the historical method of identifying a maximum number of
      staffed beds, a tool was developed to color code the PICU's admission status.
      Previous methods had been ineffective and led to confusion between the PICU
      leadership team and the administration. The tool includes the previously missing
      components of staffing and acuity, which are essential in determining admission
      capability. The PICU tool has three colored levels: green indicates open for
      admissions; yellow, admission alert resulting from available beds or because
      staffing is not equal to the projected patient numbers or required acuity; and
      red, admissions on hold because only one trauma or arrest bed is available or
      staffing is not equal to the projected acuity. Yellow and red designations
      require specific actions and the medical director's approval. The tool has been
      highly successful and significantly impacted nursing with the inclusion of the
      essential component of nurse staffing necessary in determining bed availability.

PMID- 18036476
TI  - Theory can be relevant: an overview of bioethics for the practicing child and
      adolescent psychiatrist.
AB  - Familiarity with medical ethical theory and the history of bioethics is helpful
      for the understanding of the current state of bioethics, as well as possible
      future developments that will affect physicians and patients alike. This article
      reviews major schools of thought in bioethics and their relevance to clinical
      work with children, adolescents, and families. Child and adolescent psychiatrists
      need to be familiar with major ethical issues in general medicine, psychiatry,
      and pediatrics, in addition to those controversies that are more specific to
      their subspecialty. Employing a systematic approach for the identification and
      analysis of ethical concerns, such as the Four Topics Model of Jonsen and
      colleagues, improves child and adolescent psychiatrists' confidence that they are
      aware of ethical quandaries in practice and are addressing these issues in a
      transparent, well-informed manner.

PMID- 18036477
TI  - Current ethical issues in child and adolescent psychotherapy.
AB  - Core ethical principles for the conduct of psychotherapy with children and
      adolescents transcend times, trends, and jurisdictions. Advances in technology,
      variations in state law, and the evolution of federal law should stimulate
      consideration of how these ethical principles apply to new situations; however,
      the guiding compass remains the psychotherapist's obligation to create and
      protect the integrity of the psychotherapeutic space to provide the child or
      adolescent the freedom to identify, examine, explore, and hopefully resolve the
      issues that bring one to treatment. Boundaries, privacy, confidentiality, and the
      patient's autonomy are components of this space. Together, they reflect a basic
      respect for the patient central to professional conduct and essential to any
      effective treatment process.

PMID- 18036478
TI  - Ethics of medical records and professional communications.
AB  - In child and adolescent psychiatry, medical records and professional
      communications raise important ethical concerns for the treating or consulting
      clinician. Although a distinction may be drawn between internal records (eg,
      medical records and psychotherapy notes) and external communications (eg,
      consultation reports and correspondence with pediatricians), several ethical
      principles apply to both types of documentation; however, specific considerations
      may vary, depending upon the context in which the records or communications were
      produced. Special care is due with regard to thoroughness and honesty,
      collaboration and cooperation, autonomy and dignity of the patient,
      confidentiality of the patient and family members, maintaining objectivity and
      neutrality, electronic communications media, and professional activities (eg,
      political advocacy). This article reviews relevant ethical concerns for child and
      adolescent psychiatrists with respect to medical records and professional
      communications, drawing heavily from forensic and legal sources, and offers
      additional recommendations for further reading for clarification and direction on
      ethical dilemmas.

PMID- 18036479
TI  - A doubtful guest: managed care and mental health.
AB  - This article examines the ways in which mental health services have been affected
      by managed care and describes how to address some of the ethical conflicts that
      have always existed, but have been transformed immeasurably. It outlines the
      ethical dilemmas between the competing values of mental health providers and
      managed care, as well as the practical ethical considerations related to
      confidentiality, billing, and coding. It suggests that there can be no real
      improvement for mental health providers in the ethical minefield of managed care
      until they stop focusing on how distressed they are about it and start dealing
      with the larger, systemic issues in psychiatry and American health care. The
      article concludes by noting that the only way to effect meaningful change in the
      health care system is to combine knowledge with advocacy and to proactively
      define the standards needed to make the necessary choices.

PMID- 18036480
TI  - New media and an ethics analysis model for child and adolescent psychiatry.
AB  - We and our patients are immersed in a mediascape that is unparalleled in history.
      It is a force of monumental proportion that for many youth competes with and has
      replaced parental, social, and cultural influences on their development. The
      ethical questions regarding this dynamic are frequently answered by little else
      than the application of vague and dated moral dictums based on "old media." To
      engender a comprehensive understanding of how "new media" interacts with our
      patients, we suggest a new perspective on the differentiation of old media from
      new media. Then, using our conceptual model of new media, we break down the
      ethical questions into the several overlapping ethical areas, these being media,
      professional, and bioethical. To aid in the application of the system of thought
      we provide a structured system of ethical analysis. Through these, we hope that
      this issue can be looked at with increased clarity and guidance within a
      framework for future thought.

PMID- 18036481
TI  - Ethics and the prescription pad.
AB  - This article reviews the considerations that inform ethical psychotropic
      medication prescription processes at the clinical level with child and adolescent
      patients and their families or guardians. Physician attributes, cultural and
      religious factors, and the psychodynamic aspects of psychopharmacology are
      reviewed, in addition to the applications of basic ethical principles and
      concepts to the act of dispensing psychotropic medications. Attention is given to
      the processes of informed consent, assent, and challenges encountered to ethical
      prescribing for special populations such as children in foster care and juvenile
      justice systems. Ramifications of black box warnings and off label prescribing
      are discussed. Finally, the authors offer practical tips to guide clinicians in
      ethical psychopharmacologic management of their child and adolescent patients.

PMID- 18036482
TI  - Conflicts of interest between physicians and the pharmaceutical industry and
      special interest groups.
AB  - Health care in the United States is a tangled web of competing interest groups
      beneath which ethical conflicts of interest flourish. Physicians, professional
      organizations, and academic medical centers must continually evaluate their
      relationships with the pharmaceutical industry as they relate to personal,
      professional, and institutional ethical values. This article explores the
      relevant pressing ethical issues and proposals for changing course and managing
      these potentially troublesome relationships.

PMID- 18036483
TI  - Ethical issues in psychiatric research on children and adolescents.
AB  - Psychiatric research on children and adolescents is ethically justified by the
      need to reduce the burden that mental illnesses place on young people, their
      families, and society. Such research must be conducted with careful attention to
      the ethical principles of beneficence, justice, and respect for persons. Child
      and adolescent psychiatrists who collaborate on research trials or advise
      patients and families about research participation should consider nine domains
      when evaluating the ethical acceptability of particular protocols. These domains
      include scientific merit and design; expertise, commitment, and integrity; risks
      and benefits; confidentiality; participant selection and recruitment; informed
      consent and decisional capacity; incentives; institution and peer/professional
      review; and data presentation. Special ethical issues in child and adolescent
      psychiatry research concern the use of randomized, controlled treatment trials;
      the informed consent process for research involving adolescents; the therapeutic
      misconception; and conflicts of interest in physician referrals.

PMID- 18036484
TI  - Publishing ethics in child and adolescent psychiatry: essentials for authors and
      readers.
AB  - The ethics of publishing has received negligible attention in the child and
      adolescent psychiatry literature. We examine a range of ethical problems,
      including conflict of interest, bias, publishing fraudulent or inhumane research,
      redundant publication, plagiarism, concerns about authorship, insensitive use of
      language, and special issues about publishing research involving minors.
      Strategies to improve ethical standards of publishing are proposed.

PMID- 18036485
TI  - Ethical issues in local, national, and international disaster psychiatry.
AB  - The world as we know it is plagued with conflict, yet little attention is paid to
      the inherent ethical issues and challenges related to trauma work. It is
      important to be aware of these issues because they are bound to raise questions
      about how medical practitioners confer neutrality in the face of political
      agendas and war on one hand and maintain a commitment to a person's well-being on
      the other. When engaged in local, national, or international trauma work,
      cultural, ethnic, and political literacy is crucial, and an acknowledgment of
      one's subjectivity is paramount. There are contradictory points of view about
      practicing value-free psychiatry. Psychosocial programs should examine the long
      term political consequences of their work as well as the short- and long-term
      humanitarian impact.

PMID- 18036486
TI  - Ethics education.
AB  - This article briefly describes the background and status of medical education in
      the areas of ethics and professionalism. Methods of teaching and assessment are
      described for medical students, residents, and practitioners within the core
      competency framework of medical education. Key areas of content for child and
      adolescent psychiatrists are described.

PMID- 18036487
TI  - The role of the child and adolescent psychiatrist on health care institutional
      ethics committees.
AB  - Over the past 30 years, institutional ethics committees have become the standard
      vehicle for addressing ethical issues in health care institutions. Early in this
      development, general psychiatrists became integrally involved; however, child and
      adolescent psychiatry roles on institutional ethics committees have been
      delineated less clearly. This article provides an overview of the functioning of
      institutional ethics committees, including composition and a definition of the
      roles across education, policy development, and case consultation. Within the
      context of the various roles of the institutional ethics committee, the potential
      contributions of a child and adolescent psychiatrist are defined and specific
      areas of expertise are delineated. Case examples are cited to demonstrate the
      unique contributions in the areas of developmental understanding, enhanced
      understanding of communication styles and failures, as well as an understanding
      of specific psychiatric factors and cultural issues that a child and adolescent
      psychiatrist may bring to the institutional ethics committee.

PMID- 18036488
TI  - The Ethics Committees of the American Academy of Child and Adolescent Psychiatry
      and the American Psychiatric Association: history, process, education, and
      advocacy.
AB  - The American Psychiatric Association (APA) and the American Academy of Child and
      Adolescent Psychiatry (AACAP) are the primary organizational embodiments of the
      specialties of, respectively, general psychiatry and child and adolescent
      psychiatry in the United States. Professional organizations set guidelines and
      standards for the expected behaviors of their members. To those ends, ethics
      committees were established by both the APA and the AACAP. This article describes
      how each of these organizations, via their committees, produced codes of ethics,
      and continuously provide relevant educational materials and advocacy efforts. It
      also reviews the APA ethics committee's responsibility for the evaluation of
      ethical complaints lodged against members. In closing, the article examines
      ethical dilemmas lurking on the horizon, beginning to be faced by the specialties
      and thus likely to be addressed by the committees.

PMID- 18036489
TI  - From the editor's perspective ... Poverty and human development.

PMID- 18036490
TI  - Hurricane Katrina: a personal perspective.

PMID- 18036491
TI  - Cost savings in quality improvement project to prevent venous thromboembolism.

PMID- 18036492
TI  - Thromboembolic deterrent stockings application needs regular checks.

PMID- 18036494
TI  - Case study: a minimally invasive approach to the treatment of Klippel-Trenaunay
      syndrome.
AB  - Klippel-Trenaunay syndrome (KTS) is a congenital developmental disorder
      characterized by port wine stain, venous abnormalities, soft tissue, and bony
      deformities of the affected extremity. It is usually diagnosed in early childhood
      and has many long-term sequelae. Patients not only have physical health problems
      but also must learn to cope with psychosocial factors that will affect their self
      esteem and interpersonal relationships. This article describes the syndrome of
      KTS and the minimally invasive techniques used in the treatment of superficial
      varicosities in patients with reasonably mild KTS with an intact deep venous
      system. Treating the varicosities relatively early to avoid the long-term
      complications of chronic venous insufficiency may improve the quality of life,
      maintain limb function, and decrease the risk of long-term venous complications.

PMID- 18036495
TI  - Orienting nurses to a vascular nursing specialty.
AB  - The complexity of medical and nursing care for our patients has become more
      specialized, requiring nurses to deliver care with greater understanding of
      specialty-specific disease processes. Although this paradigm shift has occurred,
      accredited nursing programs continue to prepare our nursing workforce as
      generalists. Therefore the responsibility falls onto the shoulders of the
      employer to prepare the nurse to care for specialty-specific populations soon
      after accepting a position on a specialty-specific unit. This manuscript will
      discuss a process-curriculum design through evaluation-used by an educator in a
      Magnet hospital to provide education and support to newly hired nurses for a
      vascular medical-surgical unit. Benner's Novice to Expert concept provided the
      stimulus to recognize the need for in-depth specialty knowledge and skill
      development for medical-surgical nurses to provide optimum patient care.

PMID- 18036496
TI  - Generating evidence for best nursing practice: getting your grooves.
AB  - Grooves are developmental pathways along the journey to discover new directions
      in our ever-evolving nursing careers. This is my story of how I got my grooves in
      wound and foot care and the various pathways taken toward the attainment of
      groovy--the generation of evidence for best practice nursing. I started to work
      on my first groove in 1984 after I became a gerontological clinical nurse
      specialist. Much to my delight, that groove has taken various twists and turns,
      ups and downs, with an occasional rut here and there. The journey has been most
      pleasurable and rewarding!

PMID- 18036497
TI  - The Peripheral Arterial Disease Coalition and peripheral arterial disease
      awareness campaign.

PMID- 18036498
TI  - Recommendations for evaluation of responsiveness to tetrahydrobiopterin (BH(4))
      in phenylketonuria and its use in treatment.
AB  - Some individuals with phenylketonuria (PKU) respond to pharmacologic treatment
      with tetrahydrobiopterin (BH(4)) by a reduction in the blood phenylalanine
      concentration. This can result in increased dietary tolerance for phenylalanine
      or, in rare instances, replacement of the phenylalanine-restricted diet. BH(4) is
      now available as sapropterin dihydrochloride under the name KUVAN, a formulation
      of natural BH(4). This commentary contains recommendations for determining
      responsiveness to sapropterin dihydrochloride. The recommendations include
      challenging with an initial daily dose of 20mg/kg and blood phenylalanine
      determinations pre-challenge and on days 1, 7, and 14 with the option of an
      additional continuation to day 28 if required to clarify whether a response has
      occurred. An algorithm depicting this recommendation for the challenge is
      included. The most widely accepted standard of response is > or = 30% reduction
      in the blood phenylalanine concentration, but a lower degree of response might
      also be considered clinically meaningful in some individual circumstances. Issues
      include the potential treatment of those with mild hyperphenylalaninemia who are
      not on diet, challenging neonates who have hyperphenylalaninemia identified by
      newborn screening, and the use of sapropterin dihydrochloride in treatment of
      maternal PKU pregnancies. These recommendations are intended to provide a basis
      for the use of sapropterin dihydrochloride in the treatment of PKU but may be
      altered after close observation of treated patients and carefully performed
      research.

PMID- 18036501
TI  - Right medication, right dose, right patient, right time, and right route: how do
      we select the right patient-controlled analgesia (PCA) device?
AB  - Patient safety related to medication infusion devices has received considerable
      attention recently. Critical adverse patient outcomes have resulted from
      misprogrammed delivery devices, inherent flaws in device design, and human error.
      A key strategy to improving patient safety is the development of an
      interdisciplinary team in product selection and the inclusion of registered
      nurses in the process. Such a process would include salient elements of each
      professional viewpoint and consider product impact on practice. No formal product
      selection guidelines exist which consider patient safety. This article outlines
      the process undertaken at University Health Network in the selection of its most
      recent patient-controlled analgesia device. Various available products were
      excluded from the selection process based on the interdisciplinary review.

PMID- 18036502
TI  - Evaluation of a continuous epidural analgesia program for postoperative pain in
      children.
AB  - A continuous epidural analgesia (CEA) program was developed for pediatric
      patients cared for outside of a critical care environment. Stable patients can be
      successfully monitored in the inpatient areas provided sufficient education and
      support is offered to allow for safe administration, monitoring, and evaluation
      of patient outcomes. The CEA program was developed in collaboration with the
      departments of nursing, anesthesiology, and pharmacy and was introduced on a 1
      year trial basis on the surgical patient service unit. A retrospective record
      review was conducted of patients offered CEA over the first 2 years of the
      program to determine the safety and efficacy of the program. This article
      describes the development, implementation, and evaluation of the CEA program for
      surgical patients in a tertiary pediatric hospital. The safety and efficacy of
      the program as well as the benefits, challenges, and lessons learned are
      discussed.

PMID- 18036503
TI  - Pain after tonsillectomy and adenoidectomy: "ouch it did hurt bad".
AB  - Severe pain experiences for children at home after tonsillectomy and
      adenoidectomy (T & A) have been described for more than a decade. Children and
      their parents are responsible for pain and symptom management during the
      postoperative home recovery. The purpose of this research was to more fully
      explore the pain experience and home management practices from the child's
      perspective. Diaries were used by 34 children (4-18 years of age) to document
      their pain and other symptoms. A home interview, stories, art work, and personal
      notes were also explored to fully capture the experience. From the evening of
      surgery through the second postoperative day, children reported mean pain
      intensity ratings of 3.1-3.3 out of a possible 4. Pain awakened 64.7% of the
      children from nighttime sleep and 52.9% reported vomiting associated with nausea.
      Children received an average of only 50% of the analgesic doses prescribed.
      Across the 3 postoperative days studied, pain remained severe and interventions
      offered minimal relief. Neither older children (chi(2) = 1.357, n = 13, df = 2, p
      = .259) nor younger children (chi(2) = 1.357, n = 12, df = 2, p = .507) reported
      significant differences in their mean pain intensity across the first 3
      postoperative days. Results supported concerns for inadequate home pain
      management practices in the pediatric T & A population.

PMID- 18036504
TI  - The role of urine toxicology in chronic opioid analgesic therapy.
AB  - The current trend of treating chronic nonmalignant pain with opioid therapy means
      that pain management nurses are increasingly involved in the care of patients who
      are prescribed and using potent opioid analgesics on a daily basis. Although
      demonstrated to be quite effective in certain patients, sanctioned access to
      these medications brings with it risks for abuse, addiction, and diversion. Urine
      toxicology analysis is a valuable, yet underutilized, tool to monitor patterns of
      medication use and potential use of illicit drugs to evaluate the effect of these
      on health outcomes. This review provides a guide for the use of urine toxicology
      in the nursing management of chronic pain patients on opioid therapy, detailing
      the information provided by urine toxicology analysis, the benefits and
      limitations of urine drug testing, principles of sample collection, and correct
      interpretation of findings. It is emphasized that the results of urine toxicology
      analysis should never be used in isolation to identify abuse, addiction, or
      diversion, and that patterns of medication and other drug use should always be
      evaluated with respect to evidence of improved functionality. Nurses involved in
      the care of patients with chronic pain are encouraged to consider urine
      toxicology analysis as an integral component in care plan for those on chronic
      opioid therapy, and to knowledgeably implement and interpret this powerful tool
      in the practice of pain care.

PMID- 18036505
TI  - Real-time PCR for detection of low intensity Schistosoma japonicum infections in
      a pig model.
AB  - Decades of successful Schistosoma japonicum control have increased the interest
      in how to diagnose low intensity infections. A real-time PCR assay targeting the
      mitochondrial NADH dehydrogenase I gene in S. japonicum was evaluated in infected
      pigs with very low egg output. Six out of 12 S. japonicum infected pigs were
      treated with praziquantel 8 weeks after infection and all pigs were followed for
      16 weeks post-infection. One commercial and one non-commercial extraction method
      were evaluated in combination with PCR on faecal samples. PCR with either
      extraction method were equally sensitive as the DBL-filtration/sedimentation
      technique in the acute, productive stage. PCR recovered slightly more positive
      samples in the chronic stage, but most faecal samples were negative for both PCR
      and microscopy from week 9 post-infection irrespective of treatment. IgG antibody
      titers against soluble egg antigen IgG remained high throughout the study in both
      the treated and non-treated group. PCR was consistently negative in serum and
      urine samples and negative in most of the caecal biopsies. We conclude that the
      S. japonicum faecal PCR is a highly sensitive test. However, in clinical samples
      when faecal egg output almost reaches nil in the chronic stage despite persistent
      worm burdens, both the faecal PCR and microscopy results were negative. Real-time
      PCR is less labour intensive than most microscopy methods, but has a higher
      material cost per sample.

PMID- 18036506
TI  - Tolerance of house fly, Musca domestica L. (Diptera: Muscidae) to dichlorvos (76%
      EC) an insecticide used for fly control in the tsunami-hit coastal villages of
      southern India.
AB  - The Directorate of Public Health (DPH), Tamil Nadu, in southern India employed
      spraying of dichlorvos (76% EC) for quick elimination of fly concentrations in
      the tsunami-hit coastal villages at the concentration of 304g (a.i.)/10,000m(2).
      However, nuisance of house flies remained high particularly in temporary shelters
      and centralized relief kitchens. Susceptibility of house fly, Musca domestica to
      dichlorvos was determined in the laboratory to provide information for an
      effective management of this pest. Various concentrations of dichlorvos (76% EC)
      viz., 0.1, 0.2, 0.4, 0.6 and 0.8microg (a.i.) per fly, were tested using topical
      application against F(1) progenies of house flies collected 12 months after
      insecticide applications from different habitats in the tsunami-hit coastal
      villages. Fly mortality was recorded at 24h post treatment. Parallel controls
      were maintained for comparison. Mortality of the house flies varied between 17.5%
      and 100% and increased with an increase in dosage of the insecticide. Mortality
      was >80% at 0.6 and 0.8microg (a.i.) per fly. The LD(50) of dichlorvos tested
      against flies collected from different villages varied from 0.218microg (a.i.) to
      0.235microg (a.i.) per fly and the LD(90) varied from 0.574microg (a.i.) to
      0.639microg (a.i.) per fly. House flies collected from a rural village,
      Thirukanur that had never been exposed for insecticide treatment in the past one
      decade, when tested, the mortality varied between 92.5% and 100% and increased
      with concentration of dichlorvos. Mortality was >90% from 0.2microg (a.i.) per
      fly and the LD(50) was 0.0399microg (a.i.)/fly, while the LD(90) was 0.1604microg
      (a.i.)/fly. The LD(90) values of the flies collected from the tsunami-hit
      villages were 3.5-3.9 times higher than that of the flies collected from
      Thirukanur. Fly abundance remained high in tsunami-hit villages with no marked
      reduction, suggesting that the flies had developed tolerance to dichlorvos. It is
      suggested that for an effective management of these resistant populations
      changing insecticides, application of unrelated insecticide, together with an
      appropriate environmental sanitation measure is necessary to keep the population
      under check.

PMID- 18036507
TI  - Magnetic resonance imaging diagnosis of severe fetal renal anomalies.
AB  - OBJECTIVE: The purpose of this study was to describe magnetic resonance imaging
      (MRI) findings in fetuses with severe renal anomalies. STUDY DESIGN: This was a
      case-control study that compared MRI findings in fetuses with suspected severe
      renal anomalies with gestational age-matched control fetuses. MRI was performed
      with T2-weighted single-shot fast-spin echo sequences. Each MRI was reviewed by
      an investigator who was blinded to clinical information. RESULTS: There were 2
      cases of bilateral renal agenesis, 2 cases if bilateral multicystic dysplastic
      kidney disease, 2 cases if unilateral renal agenesis and contralateral
      multicystic dysplastic kidney disease, 2 cases if polycystic kidney disease, and
      2 cases of early membrane rupture/normal kidneys. Fetuses with lethal renal
      anomalies had a characteristic bladder appearance (signal void [dark]), whereas
      control fetuses had bright signal in both bladder and renal pelvis (P < .001).
      Both cases of early membrane rupture/normal kidneys had bright bladder signal,
      but 1 case did not have bright signal in the renal pelvis. CONCLUSION: Fetuses
      with lethal renal anomalies had signal void in the bladder region on MRI.

PMID- 18036508
TI  - Remineralization effects of gum arabic on caries-like enamel lesions.
AB  - OBJECTIVE: Gum arabic is a natural polysaccharide exudate from Acacia senegal and
      other related African species of Acacia. Gum arabic is considered to have an
      ability to enhance remineralization, because of its high concentration of Ca(2+).
      However, the caries preventive capacity of gum arabic has been scarcely
      investigated. We evaluated the cariostatic activities of gum arabic using
      histopathological methods to determine its effects on remineralization. DESIGN:
      Following incubation in demineralization solution, human third molars were
      exposed to 10 mg/ml of gum arabic, sodium fluoride at 1000 ppm (NaF), or double
      distilled water (DW, negative control), then subjected to demineralization
      remineralization cycles. Before and after demineralization-remineralization
      cycles, contact microradiographs of each sample were taken and mineral
      distribution quantities were calculated. RESULTS: The remineralization ratio of
      the molars exposed to gum arabic was similar to that of those exposed to NaF,
      while the ratios of both were significantly greater than that of those exposed to
      DW. CONCLUSIONS: Gum arabic enhanced the remineralization of caries-like enamel
      lesions in vitro, suggesting its inhibitory effects towards dental caries.

PMID- 18036509
TI  - Regulation of cyclic AMP response-element binding-protein (CREB) by Gq/11-protein
      coupled receptors in human SH-SY5Y neuroblastoma cells.
AB  - Human SH-SY5Y neuroblastoma cells have been used to investigate mechanisms
      involved in CREB phosphorylation after activation of two endogenously expressed
      Gq/11-protein-coupled receptors, the M3 muscarinic acetylcholine (mACh) and B2
      bradykinin receptors. Stimulation with either methacholine or bradykinin resulted
      in maximal increases in CREB phosphorylation within 1 min, with either a rapid
      subsequent decrease (bradykinin) to basal levels, or a sustained response
      (methacholine). Inhibitor studies were performed to assess the involvement of a
      number of potential kinases in signalling to CREB phosphorylation. Removal of
      extracellular Ca2+, inhibition of Ca2+/calmodulin-dependent protein kinase II and
      down-regulation of protein kinase C (PKC) resulted in reduced CREB
      phosphorylation after both M3 mACh and B2 bradykinin receptor activation. In
      contrast, inhibition of MEK1/2 by U0126 resulted in significantly reduced CREB
      phosphorylation levels after B2 bradykinin, but not M3 mACh receptor activation.
      In addition, we demonstrate that maintained phosphorylation of CREB is necessary
      for CRE-dependent gene transcription as the M3 mACh, but not the B2 bradykinin
      receptor activates both a recombinant CRE-dependent reporter gene, and the
      endogenous c-Fos gene. These data highlight the involvement of multiple,
      overlapping signalling pathways linking these endogenous Gq/11-coupled
      metabotropic receptors to CREB and emphasize the importance of the duration of
      signalling pathway activation in converting a CREB phosphorylation event into a
      significant change in transcriptional activity.

PMID- 18036510
TI  - Reversal of chemoresistance and enhancement of apoptosis by statins through down
      regulation of the NF-kappaB pathway.
AB  - We recently found that simvastatin can modulate the nuclear factor-kappaB (NF
      kappaB) activation pathway, but whether other statins have similar effects to
      those of simvastatin is unknown. Therefore, we evaluated the effect six different
      statins on TNF-induced NF-kappaB activation in human myeloid leukemia cells. We
      then determined whether the combination of statins and standard chemotherapeutic
      agents could overcome chemoresistance and augment apoptosis. Of the six statins
      evaluated, only the natural statins (simvastatin, mevastatin, lovastatin, and
      pravastatin), not the synthetic statins (fluvastatin and atorvastatin), inhibited
      TNF-induced NF-kappaB activation. Simvastatin suppressed the NF-kappaB activation
      and potentiated the apoptosis induced by doxorubicin, paclitaxel, and 5
      fluorouracil. These results suggest that different statins behave differently
      from one another and that they may be useful in overcoming chemoresistance.

PMID- 18036511
TI  - Influence of ischemic preconditioning on levels of nerve growth factor, brain
      derived neurotrophic factor and their high-affinity receptors in hippocampus
      following forebrain ischemia.
AB  - Preconditioning of gerbil brain with a sublethal forebrain ischemia is known to
      protect hippocampal CA1 neurons following a subsequent lethal ischemia (the
      second ischemia) which usually damages neurons (ischemic tolerance). Present
      report using a confocal laser scanning microscope demonstrated that the
      hippocampal cells of sham operation gerbils contained immunofluorescent NGF and
      BDNF and their high-affinity receptors (TrkA and TrkB). A 2-min ischemia caused
      little change of these proteins (ANOVA test, P<0.05). After the second lethal
      ischemia, in the CA1 area with ischemic preconditioning (2-min ischemia), only
      BDNF but not NGF and their high-affinity receptors showed a transient reduction
      at 4 h (ANOVA test, P<0.01) and improved from 1 day (ANOVA test, P<0.05). In the
      CA1 area without ischemic preconditioning (sham operation), NGF and its high
      affinity TrkA receptor showed a consistent reduction from 4 h to 7 days (ANOVA
      test, P<0.05); BDNF and TrkB decreased transiently from 4 h to 1 day (ANOVA test,
      P<0.05) but were recovered in the surviving neurons from 3 days. At 3 and 7 days
      after the second lethal ischemia, apoptotic cell injury could be seen in the CA1
      area without ischemic preconditioning but was sparsely noted in the CA1 area with
      ischemic preconditioning. In the ischemia-resistant CA3 and dentate gyrus areas,
      only BDNF decreased significantly at 7 days in the CA3 area without ischemic
      preconditioning (ANOVA test, P<0.01). However, no significant change occurred in
      NGF, TrkA and TrkB immunofluorescence from 4 h to 7 days after the second lethal
      ischemia in the CA3 and dentate gyrus areas with and without ischemic
      preconditioning. Western blot study showed that in the hippocampal formation with
      ischemic preconditioning, preconditioning prevented the decline of these protein
      levels from 1 day to 7 days after the second lethal ischemia (ANOVA test,
      P>0.05). Results of this study demonstrate that ischemic preconditioning recovers
      the initial decline in NGF and BDNF and their corresponding receptors in the
      vulnerable CA1 neurons after the second lethal ischemia, suggesting that growth
      factors might play a role in the protective mechanism of ischemic
      preconditioning.

PMID- 18036512
TI  - Does spatiotemporal synchronization of EEG change prior to absence seizures?
AB  - We applied linear and nonlinear synchronization measures to characterize the
      synchrony between cortical regions and detect cerebral epileptic states in scalp
      EEG recordings recorded prior and during typical absence seizures. An overall
      rapid increase in the synchronization level between different cerebral regions
      was observed during the ictal state. During the interictal state, the degree of
      interdependence between EEG channels was significantly less than that observed in
      the ictal state (p<0.05). In 63% of the 35 seizures analyzed, a preictal state
      was identified by a significant decrease in the synchronization level with
      respect to the interictal state. However, in 31% of the seizures, the
      synchronization level in the preictal state was higher than that of the
      interictal state. In the remaining 6% of the seizures, no significant changes
      were found in the synchronization values in the interictal state prior to the
      seizures onset. In all the seizures analyzed, the interchannel synchrony
      persisted in the postictal state with synchronization level significantly higher
      than that observed in the interictal state. This study supports the hypothesis of
      having a focal susceptibility of the cerebral cortex prior to absence seizures
      and further underlines that this susceptibility is reproducible and patient
      specific.

PMID- 18036513
TI  - Histological evidence for drug diffusion across the cerebral meninges into the
      underlying neocortex in rats.
AB  - Transmeningeal pharmacotherapy has been proposed to treat neurological disorders
      with localized pathology, such as intractable focal epilepsy. As a step toward
      understanding the diffusion and intracortical spread of transmeningeally
      delivered drugs, the present study used histological methods to determine the
      extent to which a marker compound, N-methyl-D-aspartate (NMDA), can diffuse into
      the neocortex through the meninges. Rats were implanted with bilateral parietal
      cortical epidural cups filled with 50 mM NMDA on the right side and artificial
      cerebrospinal fluid (ACSF) in the contralateral side. After 24 h, the
      histological effects of these treatments were evaluated using cresyl violet
      (Nissl) staining. The epidural NMDA exposure caused neuronal loss that in most
      animals extended from the pial surface through layer V. The area indicated by
      this neuronal loss was localized to the neocortical region underlying the
      epidural cup. These results suggest that NMDA-like, water soluble, small
      molecules can diffuse through the subdural/subarachnoid space into the underlying
      neocortex and spread in a limited fashion, close to the meningeal penetration
      site.

PMID- 18036514
TI  - Cholesteryl ester transfer protein polymorphism D442G associated with a potential
      decreased risk for Alzheimer's disease as a modifier for APOE epsilon4 in
      Chinese.
AB  - There is compelling evidence indicating that reduction of high-density
      lipoprotein (HDL) level is associated with increased risk of Alzheimer's disease
      (AD). It is known that the levels of HDL are regulated by cholesteryl ester
      transfer protein (CETP) and several single nucleotide polymorphisms (SNPs) in the
      CETP gene have been shown to be associated with the levels of HDL. Therefore, it
      is assumed that the CETP gene is a reasonable candidate for modifying the
      susceptibility in AD. In the present study, we investigated the association of
      four CETP SNPs (D442G, L296Q, Taq1B and I405V) with the risk for sporadic AD in
      Northern Han-Chinese. One hundred and seven AD cases and 115 age and gender
      matched controls were genotyped by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP), denaturing high performance liquid chromatography
      (DHPLC) and DNA sequencing. The frequency of DG genotype (P=0.035) or G allele
      (P=0.038) for the CETP (D442G) polymorphism was greater in control subjects than
      in AD patients. The age- and sex-adjusted odds radio for DG vs. DD genotype was
      0.202 (95% CI 0.043-0.958, P=0.044). When the sample was stratified by APOE
      epsilon4 carrier status, the same tendency (P=0.042 for DG genotype, P=0.046 for
      G allele) was observed in the presence of APOE epsilon4, but not in the absence
      of APOE epsilon4 (P=0.284 for DG genotype, P=0.298 for G allele). However, these
      results became not statistically significant after correcting for multiple
      testing (Bonferroni) because of limited number of our sample. Our current results
      suggest that G allele of CETP D442G may have a potential protective effect
      against the development of AD, especially in APOE epsilon4 carriers, in Northern
      Han-Chinese, possibly through regulating the HDL level in the brain.

PMID- 18036515
TI  - Lexical learning in bilingual adults: the relative importance of short-term
      memory for serial order and phonological knowledge.
AB  - Studies of monolingual speakers have shown a strong association between lexical
      learning and short-term memory (STM) capacity, especially STM for serial order
      information. At the same time, studies of bilingual speakers suggest that
      phonological knowledge is the main factor that drives lexical learning. This
      study tested these two hypotheses simultaneously in participants with variable
      levels of English-French bilingual proficiency. A word-nonword paired-associate
      learning task was administered, with nonwords obeying French phonotactic
      patterns. French phonological knowledge was estimated by a composite French
      proficiency score summarizing productive and receptive French vocabulary
      knowledge as well as quantitative and qualitative measures of French exposure.
      STM measures maximized retention of order information (serial order
      reconstruction) or retention of phonological item information (single nonword
      delayed repetition). The French proficiency score and the serial order STM
      measure independently predicted performance on the paired-associate learning
      task. These results highlight the conjoined role of phonological knowledge and
      serial order STM in lexical learning. Importantly, serial order STM remains a
      strong predictor of lexical learning, even for bilingual individuals who have
      broad phonological knowledge.

PMID- 18036516
TI  - Arabic digit naming speed: task context and redundancy gain.
AB  - There is evidence for both semantic and asemantic routes for naming Arabic
      digits, but neuropsychological dissociations suggest that number-fact retrieval
      (2x3=6) can inhibit the semantic route for digit naming. Here, we tested the
      hypothesis that such inhibition should slow digit naming, based on the principle
      that reduced access to multiple routes would counteract redundancy gain (the
      response time advantage expected from parallel retrieval pathways). Participants
      named two single digit numbers and then performed simple addition or magnitude
      comparison (Experiment 1), multiplication or magnitude comparison (Experiment 2),
      and multiplication or subtraction (Experiment 3) on the same or on a different
      pair of digits. Addition and multiplication were expected to inhibit the semantic
      route, whereas comparison and subtraction should enable the semantic route. Digit
      naming time was approximately 15ms slower when participants subsequently
      performed addition or multiplication relative to comparison or subtraction,
      regardless of whether or not the same digit pair was involved. A letter naming
      control condition in Experiment 3 demonstrated that the effect was specific to
      digit naming. Number fact retrieval apparently can inhibit Arabic digit naming
      processes.

PMID- 18036517
TI  - Design and test of a PC-based portable three-dimensional ultrasound software
      system Ultra3D.
AB  - Currently, portable ultrasound units lack three-dimensional (3D) image display,
      limiting their potential usefulness especially under remote and hostile operating
      environments where information must be intuitive and objective. A freehand 3D
      image processing and visualization software package, Ultra3D, has been developed
      and tested, especially to work with a miniaturized linear-array transducer probe
      that is connected to a laptop PC. This paper presents the software design and
      method to integrate Ultra3D into Terason's miniaturized SmartProbe for freehand
      3D ultrasound imaging. Since images generated by Ultra3D are in a digital imaging
      and communications in medicine (DICOM) format, data sharing with others is easy.

PMID- 18036518
TI  - Divergent and conserved roles of extradenticle in body segmentation and appendage
      formation, respectively, in the cricket Gryllus bimaculatus.
AB  - The cricket Gryllus bimaculatus is a typical hemimetabolous intermediate germ
      insect, in which the processes of segmentation and appendage formation differ
      from those in Drosophila, a holometabolous long germ insect. In order to compare
      their developmental mechanisms, we have focused on Gryllus orthologs of the
      Drosophila developmental regulatory genes and studied their functions. Here, we
      report a functional analysis of the Gryllus ortholog of extradenticle (Gb'exd)
      using embryonic and parental RNA interference (RNAi) techniques. We found the
      following: (1) RNAi suppression of Gb'exd results in the deletion or fusion of
      body segments. Especially the head was often very severely affected. This gap
      like phenotype may be related to reduced expression of the gap genes hunchback
      and Kruppel in early RNAi germbands. (2) In the appendages, several segments
      (podomeres) were fused. (3) Head appendages including the antenna were
      transformed to a leg-like structure consisting of at least one proximal podomere
      as well as several tarsomeres. The defects in appendages are reminiscent of the
      phenotype caused by large exd clones in Drosophila antennal discs. These findings
      led us to the conclusion that (1) Gb'exd is required for segment patterning in
      the gnathal to abdominal region, acting in a gap gene-like manner in the anterior
      region. (2) Gb'exd plays important roles in formation of the appendages and the
      determination of their identities, acting as a regulatory switch that chooses
      between the fates of head appendages versus the appendage ground state. Although
      functions of Gb'exd in appendage patterning appear fundamentally conserved
      between Gryllus and Drosophila, its role in body segmentation may differ from
      that of Drosophila exd.

PMID- 18036519
TI  - Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1.
AB  - Riluzole exerts a neuroprotective effect through different mechanisms, including
      action on glutamatergic transmission. We investigated whether this drug affects
      glutamate transporter-mediated uptake, using clonal cell lines stably expressing
      the rat glutamate transporters GLAST, GLT1 or EAAC1. We found that riluzole
      significantly increased glutamate uptake in a dose-dependent manner; kinetic
      analysis indicated that the apparent affinity of glutamate for the transporters
      was significantly increased, with similar effects in the three cell lines. This
      may facilitate the buffering of excessive extracellular glutamate under
      pathological conditions suggesting that riluzole's neuroprotective action might
      be partly mediated by its activating effect on glutamate uptake.

PMID- 18036520
TI  - Myogenic tone and reactivity of cerebral arteries in type II diabetic BBZDR/Wor
      rat.
AB  - BBZDR/Wor rat is a new model of type II diabetes with spontaneous obesity and
      clinical characteristics close to human diabetes. In this study the time-course
      of cerebroarterial dysfunction was characterized. Posterior cerebral arteries
      from BBZDR/Wor rats and their age-matched lean controls were pressurized to 70 mm
      Hg in an arteriograph. Effects of intraluminal pressure and different
      pharmacological agents on myogenic tone were evaluated. Pressure-myogenic tone
      curves in diabetic arteries were similar to that in non-diabetic arteries at pre
      diabetic age, showed leftward shift at 4 weeks and were significantly different
      with higher myogenic tone at 5 and 8 months of diabetes. Age-dependent decrease
      in myogenic tone was observed in non-diabetic arteries. Dilation to histamine was
      similar to that in non-diabetic arteries at pre-diabetic and at 4 weeks but
      significantly reduced at 5 and 8 months of diabetes. Bradykinin-mediated dilation
      was significantly reduced in early and chronic diabetes, whereas (+/-)-S-nitroso
      N-acetylpenicillamine (SNAP)-mediated dilation was decreased modestly at 8 months
      of diabetes. Sensitivity and constriction to 5-hydroxytryptamine were increased
      in early and chronic diabetes. Responses to bradykinin and 5-hydroxytryptamine
      were decreased and increased, respectively. Myogenic tone was significantly less
      sensitive to (lower pIC(50)) U-73122 than normal arteries at 4 weeks and 8 months
      of diabetes suggesting an increased activation of phospholipase C (PLC). This
      study shows that pressure-mediated autoregulation of cerebral arteries in type II
      diabetes operates at higher resistance. Endothelium-dependent dilation was
      decreased with chronic diabetes with increased sensitivity to constrictor
      agonist. Endothelium-independent dilation was modestly affected. Arterial hyper
      reactivity to pressure and constrictor agonist were likely due to increased PLC
      activation.

PMID- 18036521
TI  - Modulation of SRF-dependent gene expression by association of SPT16 with MKL1.
AB  - MKL1 (MRTF-A/MAL) is a member of the myocardin-related transcription factor
      family that plays a key role in the development and differentiation of smooth
      muscle cells (SMCs) via activation of serum response factor (SRF)-dependent SMC
      gene expression. MKL1 associates with SRF and stimulates its transcriptional
      activity. Here, by performing matrix-assisted laser desorption/ionization-time of
      flight mass spectrometric analysis combined with in vitro glutathione S
      transferase pull-down assay, we identified 4 candidate proteins that associate
      with MKL1 through the N-terminus region of MKL1. SPT16, ATP citrate lyase,
      nucleolin and radixin were identified, and the physical and functional
      interactions between MKL1 and SPT16 were examined. SPT16 is a component of the
      FACT (facilitating chromatin transcription) complex that allows RNA polymerase II
      to traverse the nucleosomes. SPT16 associates with MKL1 in vitro and in vivo;
      moreover, SSRP1, another component of the FACT complex, associates with the N
      terminus region of MKL1 in vitro. SPT16 synergistically activates the
      transcriptional activity of MKL1. These results show that the expression of
      nucleosomal SRF-dependent genes, including the SMC gene, is activated by MKL1 via
      activation of SRF and recruitment of the FACT complex.

PMID- 18036523
TI  - High-efficacy site-directed drug delivery system using sialyl-Lewis X conjugated
      liposome.
AB  - The aim of this study was to evaluate the new developed sialyl-Lewis X conjugated
      liposome (sLe XL) as a site-directed delivery system to activated endothelial
      cells in vivo using a murine experimental autoimmune uveoretinitis (EAU) model.
      Four types of nanoparticles were prepared using this liposome: fluorescein
      isothiocyanate (FITC) labeled sLe XL (F-sLe XL) and its vehicle (F-L), sLe XL
      containing dexamethasone (d-sLe XL) and liposome without sLe X containing
      dexamethasone (d-L). First, after a bolus injection of F-sLe XL or F-L into EAU
      mice, sequential tissue accumulation of FITC was examined by confocal laser
      scanning microscopy. Second, anti-E-selectin antibody, as a blocking antibody,
      was given intravenously to EAU mice prior to the injection of F-sLe XL in order
      to investigate the effect of the antibody on inhibition of the accumulation of F
      sLe XL. Third, concentration of dexamethasone in several organs after the
      injection of d-sLe XL (total dexamethasone 2 microg) or free dexamethasone
      solution (1mg) was measured by radioimmunoassay. Accumulation of FITC was only
      observed in F-sLe XL treated EAU mice. F-sLe XL accumulated on the activated
      endothelial cells within 5 min; accumulation then was inhibited using anti-E
      selectin antibody. The FITC color was dispersed sequentially to the entire
      retina. d-sLe XL showed selective targeting to the inflamed eye, where an
      approximately two-fold higher dexamethasone concentration was achieved compared
      with 1mg free dexamethasone. sLe XL can be a highly efficacious site-directed
      system in vivo. Using sLe XL as a vehicle for drug delivery, substantial
      pharmacologic effects with minimum side effects in inflammatory diseases should
      be achieved.

PMID- 18036522
TI  - Neural crest motility on fibronectin is regulated by integrin activation.
AB  - Cell migration is essential for proper development of numerous structures derived
      from embryonic neural crest cells (NCCs). Although recent work has shown that
      receptor recycling plays an important role in NCC motility on laminin, the
      molecular mechanisms regulating NCC motility on fibronectin remain unclear. One
      mechanism by which cells regulate motility is by modulating the affinity of
      integrin receptors. Here, we provide evidence that cranial and trunk NCCs rely on
      functional regulation of integrins to migrate efficiently on fibronectin (FN) in
      vitro. For NCCs cultured on fibronectin, velocity decreases after Mn2+
      application (a treatment that activates all surface integrins) while velocity on
      laminin (LM) is not affected. The distribution of activated integrin beta 1
      receptors on the surface of NCCs is also substratum-dependent. Integrin
      activation affects cranial and trunk NCCs differently when cultured on different
      concentrations of FN substrata; only cranial NCCs slow in a FN concentration
      dependent manner. Furthermore, Mn2+ treatment alters the distribution and number
      of activated integrin beta 1 receptors on the surface of cranial and trunk NCCs
      in different ways. We provide a hypothesis whereby a combination of activated
      surface integrin levels and the degree to which those receptors are clustered
      determines NCC motility on fibronectin.

PMID- 18036524
TI  - Placebo-controlled chronic high-frequency stimulation of the subthalamic nucleus
      preserves dopaminergic nigral neurons in a rat model of progressive Parkinsonism.
AB  - Chronic high-frequency stimulation (HFS) of the subthalamic nucleus (STN)
      protects nigral dopaminergic neurons from neurodegeneration in animal models of
      Parkinson's disease (PD). However, these data are challenged by the lack of
      control for neuroprotective effects that might be related to tissue damage due to
      electrode insertion or STN-HFS. Here we report the first placebo-controlled study
      on continuous STN-HFS in a rat model of PD using an implantable microstimulation
      system. We found a significant increase of preserved dopaminergic nigral neurons
      on the lesioned side (expressed as ratio to the non-lesioned side) of
      approximately 50% in comparison to STN sham-stimulated and STN-naive rats. These
      data provide evidence for the phenotypic rescue of nigral dopamine neurons by
      long-term STN-HFS in this animal model of PD.

PMID- 18036525
TI  - A new approach to chromosomal abnormalities in sperm from patients with
      oligoasthenoteratozoospermia: detection of double aneuploidy in addition to
      single aneuploidy and diploidy by five-color fluorescence in situ hybridization
      using one probe set.
AB  - OBJECTIVE: To determine the frequencies of disomy, nullisomy, total aneuploidy,
      and diploidy in the sperms of infertile men. DESIGN: A controlled prospective
      study. SETTING: Assisted reproductive technology (ART)/IVF Unit and Department of
      Medical Biology and Genetics, Meram Medical Faculty, Konya, Turkey. PATIENT(S):
      Infertile men with oligoasthenoteratozoospermia (OAT) and normal fertile donors.
      INTERVENTION(S): After slide preparation from semen samples, sperm nuclei were
      analyzed for chromosomes 13, 18, 21, X, and Y by five-color fluorescence in situ
      hybridization. MAIN OUTCOME MEASURE(S): The sperm aneuploidy (disomy and
      nullisomy) and diploidy rates were determined according to the number of signals
      detected for each probe in infertile and fertile men. RESULTS: Patients with OAT
      had a significantly higher incidence of disomy (except chromosome 18 and XX
      disomy), nullisomy (except chromosome 18), and diploidy than normal fertile
      controls. In addition to double disomy, double nullisomy and disomy+nullisomy
      were observed in patients with OAT, but none of these were seen in controls.
      CONCLUSION(S): In this study patients with OAT had an increased rate of sperm
      aneuploidy and diploidy. This finding suggest that patients with OAT may be at an
      increased risk of producing aneuploid and triploid offsprings. For this reason,
      it may be very important to perform the sperm fluorescence in situ hybridization
      in patients with OAT. Thus, a more informative genetic counseling might be given
      to couples with male factor infertility who are at an increased risk of having
      aneuploid offsprings and triploid conceptions before intracytoplasmic sperm
      injection (ICSI).

PMID- 18036526
TI  - Repeatability of baseline corticosterone concentrations.
AB  - One major assumption for endocrine studies is that hormone titers are consistent
      within an individual so that if hormone titers are low relative to the cohort on
      one day, they are relatively low compared to the cohort on other days. This is an
      especially important assumption for most field studies where researchers may have
      access to an individual animal only once. We used a laboratory study with captive
      house sparrows (Passer domesticus) to test this assumption using glucocorticoid
      titers. Baseline corticosterone titers were measured five different times for
      each bird under six different experimental conditions: during both day and night
      while birds were held on a short day photoperiod (11L, 13D), a long day
      photoperiod (19L, 5D), and while birds were undergoing a prebasic molt. Although
      the variation within an individual was often larger than the variation between
      individuals, the relative ranks of birds compared to their cohort were consistent
      during the night in all three conditions. In contrast, during the day the
      relative ranks of birds compared to their cohorts were only consistent on short
      days; on long days and during molt there was no significantly consistent ranking
      among individuals. Furthermore, the overall rank of an individual in its cohort
      was often different during the day and night. These data indicate that it is not
      always a good assumption that birds can be categorized as individuals with higher
      and lower titers, which will complicate analyses of the causes of interindividual
      variation.

PMID- 18036528
TI  - Promoting the art of caring for older people.

PMID- 18036529
TI  - Kinetic and mutational analysis of the Trypanosoma brucei NBT1 nucleobase
      transporter expressed in Saccharomyces cerevisiae reveals structural similarities
      between ENT and MFS transporters.
AB  - Parasitic protozoa are unable to synthesise purines de novo and thus depend on
      the uptake of nucleosides and nucleobases across their plasma membrane through
      specific transporters. A number of nucleoside and nucleobase transporters from
      Trypanosoma brucei brucei and Leishmania major have recently been characterised
      and shown to belong to the equilibrative nucleoside transporter (ENT) family. A
      number of studies have demonstrated the functional importance of particular
      transmembrane segments (TMS) in nucleoside-specific ENT proteins. TbNBT1, one of
      only three bona fide nucleobase-selective members of the ENT family, has
      previously been shown to be a high-affinity transporter for purine nucleobases
      and guanosine. In this study, we use the Saccharomyces cerevisiae expression
      system to build a biochemical model of how TbNBT1 recognises nucleobases. We next
      performed random in vitro and site-directed mutagenesis to identify residues
      critical for TbNBT1 function. The identification of residues likely to contribute
      to permeant binding, when combined with a structural model of TbNBT1 obtained by
      homology threading, yield a tentative three-dimensional model of the transporter
      binding site that is consistent with the binding model emerging from the
      biochemical data. The model strongly suggests the involvement of TMS5, TMS7 and
      TMS8 in TbNBT1 function. This situation is very similar to that concerning
      transporters of the major facilitator superfamily (MFS), one of which was used as
      a template for the threading. This point raises the possibility that ENT and MFS
      carriers, despite being considered evolutionarily distinct, might in fact share
      similar topologies and substrate translocations pathways.

PMID- 18036530
TI  - Strain shielding in proximal tibia of stemmed knee prosthesis: experimental
      study.
AB  - Theoretical concerns about the use of cemented or press-fit stems in revision
      total knee arthroplasty (TKA) include stress shielding with adverse effects on
      prosthesis fixation. Revision TKA components are commonly stemmed to protect the
      limited autogenous bone stock remaining. Revision procedures with the use of
      stems can place abnormal stresses through even normal bone by their constrained
      design, type of materials and fixation method and may contribute for bone loss.
      Experimental quantification of strain shielding in the proximal synthetic tibia
      following TKA is the main purpose of the present study. In this study, cortical
      bone strains were measured experimentally with tri-axial strain gauges in
      synthetic tibias before and after in vitro knee surgery. Three tibias were
      implanted with cemented and press-fit stem augments and solely with a tibial tray
      (short monobloc stem) of the P.F.C. Sigma Modular Knee System. The difference
      between principal strains of the implanted and the intact tibia was calculated
      for each strain gauge position. The results demonstrated a pronounced strain
      shielding effect in the proximal level, close to tibial tray with the cemented
      stem augment. The press-fit stem presented a minor effect of strain shielding but
      was more extensively throughout the stem. An increase of strains closely to the
      distal tip of the cemented and the press-fit stem augment was observed. This
      suggests for a physiological condition, a potential effect of bone resorption at
      the proximal region for the cemented stem augment. The localized increase of
      strains in stems tip can be related with the clinical finding of the pain, at the
      end of stem after revision TKA.

PMID- 18036531
TI  - Finite element modelling of primary hip stem stability: the effect of
      interference fit.
AB  - The most commonly reported complications related to cementless hip stems are
      loosening and thigh pain; both of these have been attributed to high levels of
      relative micromotion at the bone-implant interface due to insufficient primary
      fixation. Primary fixation is believed by many to rely on achieving a sufficient
      interference fit between the implant and the bone. However, attempting to achieve
      a high interference fit not infrequently leads to femoral canal fracture either
      intra-operatively or soon after. The appropriate range of diametrical
      interference fit that ensures primary stability without risking femoral fracture
      is not well understood. In this study, a finite element model was constructed to
      predict micromotion and, therefore, instability of femoral stems. The model was
      correlated with an in vitro micromotion experiment carried out on four cadaver
      femurs. It was confirmed that interference fit has a very significant effect on
      micromotion and ignoring this parameter in an analysis of primary stability is
      likely to underestimate the stability of the stem. Furthermore, it was predicted
      that the optimal level of interference fit is around 50 microm as this is
      sufficient to achieve good primary fixation while having a safety factor of 2
      against femoral canal fracture. This result is of clinical relevance as it
      indicates a recommendation for the surgeon to err on the side of a low
      interference fit rather than risking femoral fracture.

PMID- 18036533
TI  - Surfactant coated graphitic carbon based stationary phases for anion-exchange
      chromatography.
AB  - Separations of common inorganic anions were carried out on three different
      surfactant coated media using carbonate/bicarbonate eluents with suppressed
      conductivity detection. Graphitic carbon columns (porous graphitic carbon and
      carbon-clad zirconia) packed with 3 microm particles have been converted into
      anion-exchange stationary phases by equilibration with the cationic surfactants:
      didodecyldimethylammonium bromide (DDAB); cetyltrimethylammonium bromide (CTAB);
      and cetylpyridinium chloride (CPC). Additionally, an ethylene-bridged silica
      column was studied with CPC coatings. Porous graphitic carbon (PGC) columns
      coated with DDAB exhibited pressure increases and loss of resolution at higher
      capacities. CPC coatings on PGC exhibited better repeatability and efficiencies
      of 5.0 x 10(4)plates/m. However, CPC coatings exhibited a 15% loss in retention
      factor with <1.2 x 10(3) column volumes on PGC. Conversely, the ethylene-bridged
      silica column showed complete failure in less than 8 h of use. As with PGC,
      carbon-clad zirconia coated with CPC showed an initial loss of capacity, but
      thereafter was stable for more than 1.7 x 10(3) column volumes (t(r) RSD<2%).

PMID- 18036532
TI  - Coronary artery flow measurement using navigator echo gated phase contrast
      magnetic resonance velocity mapping at 3.0 T.
AB  - A validation study and early results for non-invasive, in vivo measurement of
      coronary artery blood flow using phase contrast magnetic resonance imaging (PC
      MRI) at 3.0T is presented. Accuracy of coronary artery blood flow measurements by
      phase contrast MRI is limited by heart and respiratory motion as well as the
      small size of the coronary arteries. In this study, a navigator echo gated, cine
      phase velocity mapping technique is described to obtain time-resolved velocity
      and flow waveforms of small diameter vessels at 3.0T. Phantom experiments using
      steady, laminar flow are presented to validate the technique and show flow rates
      measured by 3.0T phase contrast MRI to be accurate within 15% of true flow rates.
      Subsequently, in vivo scans on healthy volunteers yield velocity measurements for
      blood flow in the right, left anterior descending, and left circumflex arteries.
      Measurements of average, cross-sectional velocity were obtainable in 224/243
      (92%) of the cardiac phases. Time-averaged, cross-sectional velocity of the blood
      flow was 6.8+/-4.3cm/s in the LAD, 8.0+/-3.8cm/s in the LCX, and 6.0+/-1.6cm/s in
      the RCA.

PMID- 18036534
TI  - Using the liquid nature of the stationary phase in counter-current chromatography
      V. The back-extrusion method.
AB  - The main feature of counter-current chromatography (CCC) is that the stationary
      phase is a liquid as well as the mobile phase. The retention volumes of solutes
      are directly proportional to their distribution coefficients K(D) in the biphasic
      liquid system used in the CCC column. Solutes with high K(D) coefficients are
      highly retained in the column. The back-extrusion method (BECCC) uses the fact
      that the liquid stationary phase, that contains the retained solutes, can be
      easily moved. Switching the column inlet and outlet ports without changing the
      liquid phase used as the mobile phase causes the rapid collapse of the two
      immiscible liquid phases inside the column, the previously stationary phase being
      gathered at the new column outlet. Then this previously stationary liquid phase
      is extruded outside the CCC column carrying the retained solutes. The back
      extrusion method is tested with a standard mixture of five compounds and compared
      with the recently described elution-extrusion method. It is shown that the
      chromatographic resolution obtained during the back-extrusion step is good
      because the solute band broadening is minimized as long as the solute is located
      inside the "stationary" phase. However, a major drawback of the BECCC method is
      that all solutes are split between the liquid phases according to their
      distribution ratios when the CCC column equilibrium is broken. The change of
      flowing direction should be done after a sufficient amount of mobile phase has
      flushed the column in the classical mode, eluting solutes with small and medium
      distribution ratios. Otherwise, a significant portion of the solutes will stay in
      the mobile phase inside the column and produce a broad peak showing after the
      stationary phase extrusion.

PMID- 18036535
TI  - Characterization and applications of reversed-phase column selectivity based on
      the hydrophobic-subtraction model.
AB  - A total of 371 reversed-phase columns have now been characterized in terms of
      selectivity, based on five solute-column interactions (the hydrophobic
      subtraction model). The present study illustrates the use of these data for
      interpreting peak-tailing and column stability. New insights are also provided
      concerning column selectivity as a function of ligand and silica type, and the
      selection of columns for orthogonal separations is re-examined. Some suggestions
      for the quality control of reversed-phase columns during manufacture are offered.

PMID- 18036536
TI  - 13th International Symposium on Separation Sciences. Preface.

PMID- 18036537
TI  - Step gradients in 3-zone simulated moving bed chromatography. Application to the
      purification of antibodies and bone morphogenetic protein-2.
AB  - The simulated moving bed (SMB) technology is a proven tool for efficient
      separation of binary mixtures. However, relying on isocratic conditions limits
      the applicability of the classical SMB approach when considering the field of
      bioseparations. Here, the use of gradients opens up new possibilities. A gradient
      in a SMB process can be established by using different solvent strengths in the
      incoming feed and desorbent streams, resulting in two internal plateaus of
      elution strength. Thus, compared to the conventional process, the overall amount
      of solvent needed can be reduced, productivity can be increased and more
      concentrated product streams can be obtained. In this contribution, two case
      studies will be presented. At first, the separation of bovine IgG from lysozyme
      will be analyzed as a model system. Antibodies are a common target substance in
      bio-chromatography, as therapeutic monoclonal antibodies are among the most
      promising biopharmaceuticals. Using adsorption data obtained from single-column
      experiments, an appropriate SMB process was designed and implemented. The second
      target component is the active dimeric form of the bone morphogenetic protein-2
      (BMP-2). This protein was isolated from a renaturation solution, which also
      contained its inactive monomeric form as well as other undefined proteins from
      the bacterial production strain. A 3-zone open-loop gradient-SMB approach was
      used successfully for both separations.

PMID- 18036538
TI  - Online in situ analysis of selected semi-volatile organic compounds in water by
      automated microscale solid-phase extraction with large-volume injection/gas
      chromatography/mass spectrometry.
AB  - A fully automated analytical method was developed for the online in situ analysis
      of selected semi-volatile organic compounds in water. The method used a large
      volume injection/gas chromatography/mass spectrometry coupled with a fully
      automated microscale solid-phase extraction technique, which was based on x-y-z
      robotic techniques. Water samples were extracted by using a 96-well solid-phase
      extraction plate. For most analytes included in this study, the obtained linear
      calibrations ranged from 0.05 to 5.0 microg/L with correlation coefficients of
      0.996-1.000, the method detection limits were less than 0.1 microg/L, and the
      relative recoveries were in the range of 70-120% with a relative standard
      deviation of less than 15% for fortified reagent water samples. The applications
      to chlorinated tap water, well water, and river water have been validated. The
      obtained results were similar to those resulting from fortified reagent water
      samples for all analytes except metribuzin, bromacil, aldrin, and methoxychlor.
      Matrix effects were observed for these analytes. In general, this fully automated
      analytical method was rugged, reliable, and easy to operate, and was capable of
      providing real-time data to water treatment and distribution systems as well as
      water reservation and protection systems. In addition, the method could reduce
      the analytical costs associated with sample collection, transportation, storage,
      and preparation.

PMID- 18036539
TI  - Synthesis, amino-functionalization of mesoporous silica and its adsorption of
      Cr(VI).
AB  - Mesoporous silica materials with a centered rectangular symmetry (cmm) have been
      synthesized through a facile direct-templating method using
      tetraethylorthosilicate (TEOS) and amphiphilic block co-polymers Pluronic P123
      under acidic conditions. The amino groups have been grafted to as-synthesized
      mesoporous silica by [1-(2-amino-ethyl)-3-aminopropyl]trimethoxysilane (AAPTS).
      Thus obtained amino-functionalized mesoporous silica (denoted as NN-silica) was
      used for sequestration of Cr(VI) from aqueous solution. After sequestration of
      Cr(VI), the sample was denoted as Cr(VI)-silica. The parent mesoporous silica, NN
      silica and Cr(VI)-silica were characterized by X-ray powder diffraction (XRD),
      transmission electron microscopy (TEM), scanning electron microscopy (SEM),
      Fourier-transform infrared spectroscopy (FTIR) and N(2) adsorption-desorption
      isotherms. XRD and TEM results confirm that the structure of these samples is
      centered rectangular symmetry (cmm). N(2) adsorption-desorption isotherms show
      that there is a remarkable decrease in surface area and pore volume for NN-silica
      (S(BET)=54.5 m(2)g(-1), V(P)=0.09 cm(3)g(-1)) and Cr(VI)-silica (S(BET)=53.2
      m(2)g(-1), V(P)=0.07 cm(3)g(-1)) compared to the parent mesoporous silica
      (S(BET)=444.0 m(2)g(-1), V(P)=0.71 cm(3)g(-1)). The BJH desorption average
      diameter of NN-silica, Cr(VI)-silica and the parent mesoporous silica is 4.40 nm,
      4.07 nm and 5.11 nm, respectively. The results reveal the channels of as
      synthesized mesoporous silica are essentially grafted with abundant amino groups
      and loaded with Cr(VI). The adsorption experiment results show that the
      functionalized mesoporous silica materials possess an increased Cr(VI) adsorption
      capacity and the maximum Cr(VI) loadings at 25, 35 and 45 degrees C can reach
      2.28, 2.86 and 3.32 mmol/g, respectively.

PMID- 18036540
TI  - Blockades of phospholipase A(2) and platelet-activating factor receptors reduce
      the hemocyte phagocytosis in Rhodnius prolixus: in vitro experiments.
AB  - The hemocytes phagocytosis in response to microorganisms may play an important
      role in the cellular immune responses of insects. Here, we have evaluated the
      effects of the platelet-activating factor (PAF) and eicosanoids in the
      phagocytosis of hemocyte monolayers of Rhodnius prolixus to the yeast
      Saccharomyces cerevisiae. Experiments showed that the phagocytosis of yeast cells
      by Rhodnius hemocytes is very efficient in both controls and cells treated with
      PAF and arachidonic acid. Phagocytosis of yeast particles is significantly
      blocked when the specific phopholipase A(2) inhibitor, dexamethasone, is applied
      on the hemocytes. By contrast, dexamethasone-pretreated hemocyte monolayers
      exhibit a drastic increase in the quantity of yeast cell-hemocyte internalization
      when the cells are treated by arachidonic acid. In addition, phagocytosis
      presents significant reduction in hemocyte monolayers treated with a specific PAF
      receptor antagonist, WEB 2086. Nevertheless, inhibition of phagocytosis with WEB
      2086 is counteracted by the treatment of the hemocyte monolayers with PAF. In
      conclusion, phagocytosis of yeast cells by hemocytes is related to the activation
      of PAF receptors and eicosanoid pathways in the bloodsucking bug, R. prolixus.

PMID- 18036541
TI  - Predicting the magnitude of the reflex response to insertions in ubiquitin.
AB  - The ability to predict the structural response of a protein to an insertion would
      be a significant advance for the fields of homology modeling and protein design.
      However, the effects of insertions on protein conformation are not well
      understood. Previous work has demonstrated that for two loops in ubiquitin, the
      primary determinant of the structural adaptation to insertions is the insertion
      site rather than the sequence of the insertion; this phenomenon was termed the
      reflex response of loops to insertions. We report herein the analysis of
      ubiquitin mutants with insertions in two other loops. This study demonstrates
      that the insertion site is the primary determinant of the response to insertions
      for these two new loops as well, which further supports the reflex response
      hypothesis. We also attempted to predict the relative magnitudes of the responses
      at each site but were unsuccessful. Using the additional data collected in this
      work, we have refined our predictive hypothesis.

PMID- 18036542
TI  - The Escherichia coli TatABC system and a Bacillus subtilis TatAC-type system
      recognise three distinct targeting determinants in twin-arginine signal peptides.
AB  - The Tat system transports folded proteins across bacterial and thylakoid
      membranes. In Gram-negative organisms, it is encoded by tatABC genes and the
      system recognizes substrates bearing signal peptides with a conserved twin
      arginine motif. Most Gram-positive organisms lack a tatB gene, indicating major
      differences in organisation and/or mechanism. Here, we have characterized the
      essential targeting determinants that are recognized by a Bacillus subtilis TatAC
      type system, TatAdCd. Substitution by lysine of either of the twin-arginine
      residues in the TorA signal peptide can be tolerated, but the presence of twin
      lysine residues blocks export completely. We show that additional determinants
      can be as important as the twin-arginine motif. Replacement of the -1 serine by
      alanine, in either the TorA or DmsA signal peptide, almost blocks export by
      either the B. subtilis TatAdCd or Escherichia coli TatABC systems, firmly
      establishing the importance of this -1 residue in these signal peptides.
      Surprisingly, the +2 leucine in the DmsA signal peptide (sequence SRRGLV) appears
      to play an equally important role and substitution by alanine or phenylalanine
      blocks export by both the B. subtilis and E. coli systems. These data identify
      three distinct determinants, whose importance varies depending on the signal
      peptide in question. The data also show that the B. subtilis TatAdCd and E. coli
      TatABC systems recognize very similar determinants within their target peptides,
      and exhibit surprisingly similar responses to mutations within these
      determinants.

PMID- 18036543
TI  - P75 nerve growth factor receptor is expressed in regenerating human nerve grafts.
AB  - BACKGROUND: The purpose of this study was to elucidate the expression of p75
      nerve growth factor receptor (p75NGFR) in human cross-facial nerve grafts and to
      compare the immunohistological findings with patient data and the functional
      outcome in facial reanimation. MATERIALS AND METHODS: The study comprised 37
      sural nerve graft specimens. All of the patients had long-lasting complete facial
      paralysis and were operated on by the standard two-stage procedure involving
      cross-facial nerve grafts and microneurovascular muscle transfer. Nerve biopsies
      were taken 4 to 20 months (mean, 8 months) after the cross-facial nerve grafting.
      Immunohistochemistry for p75NGFR as well as for Schwann cells (S-100; Dako,
      Glostrup, Denmark) and for Neurofilament-200 (NF-200; Boehringer, Mannheim,
      Germany) was performed. RESULTS: In graft biopsies, the mean number of NF-200
      positive axons amounted to 38% (range, 6-81%) of that in control samples.
      Further, regenerated axons were thinner than in control samples. Morphologically,
      the grafted nerves were characterized by fibrosis and invasion of inflammatory
      cells. A longer time between cross-facial nerve grafting and biopsy sampling
      correlated with a higher number of viable axons (NF-200) (P = 0.002). In all
      cases, expression of p75NGF receptor was clearly higher at the distal end of the
      grafted nerve. Expression of p75NGFR was lower in older than in younger patients
      (P = 0.003). A high expression of p75NGFR was often seen with better function of
      the transplanted muscle. CONCLUSION: Increased expression of p75NGFR in human
      nerve grafts was noted, especially in younger patients. We suggest that p75NGFR
      expression might be a contributing factor in a successful axonal regeneration and
      eventual recovery of muscle function.

PMID- 18036544
TI  - The right heart and its distinct mechanisms of development, function, and
      failure.
AB  - Congestive heart failure is the most common cause of hospitalization in the
      United States for people over the age of sixty-five. As the population ages, the
      morbidity and mortality from heart failure will become more prevalent. Left heart
      failure has been, and continues to be, extensively studied. However, a recent
      report from the National Heart, Lung, and Blood Institute suggests that the right
      heart has been relatively under-investigated, and unfortunately, most of the
      basic mechanisms of intracellular signaling within the right heart still remain
      poorly understood. Right heart failure is now being increasingly recognized as
      distinctly different from left heart failure, and an important mediator of
      overall cardiovascular collapse. The purpose of this review, therefore, is to
      discuss the current understanding of right heart cellular development,
      physiology, and pathophysiology, as well as to review therapeutic interventions
      that are both currently available and under investigation.

PMID- 18036545
TI  - How good is good? Human values and Europe's proposed Marine Strategy Directive.
AB  - The adoption of the proposed European Marine Strategy Directive is an opportunity
      for a comprehensive policy for protecting, improving and sustainably using
      Europe's environmentally degraded seas. It calls for an ecosystem-based approach
      to management where humans are regarded as a key system component. Although the
      proposed wording has been the subject of fierce debate, the central policy goal
      remains achieving "Good Environmental Status". The interpretation of "good" is
      key to implementation and relates to human values and worldviews. We demonstrate
      how these vary widely across Europe. Solution of fundamental considerations such
      as the assignation of reference states, the balance between precautionary and
      evidence-based action, the degree of subsidiarity, and conservation strategies
      including marine protected areas, will ultimately depend upon public
      understanding, involvement in and support for the Directive. The social element,
      critical to effective adaptive management, requires greater attention within the
      context of a regional seas geographical framework.

PMID- 18036546
TI  - Removal of organotin compounds, Cu and Zn from shipyard wastewaters by adsorption
      -flocculation: a technical and economical analysis.
AB  - Several commercially available adsorbents were screened for their ability to
      remove Cu, Zn and organotin compounds from both artificial contaminated and real
      dockyard wastewater. An adsorption--flocculation process using a mixture of two
      adsorbents (a clay based adsorbent and a powdered activated carbon) was optimized
      for an optimal adsorbent and pollutant removal. At the optimal conditions the
      process was evaluated with both artificial and real shipyard wastewater, and the
      cost of the adsorption-flocculation process with relation to different influent
      concentrations and discharge limits was estimated.

PMID- 18036547
TI  - Chemiluminescence flow-through biosensor for glucose with eggshell membrane as
      enzyme immobilization platform.
AB  - In this study, a new chemiluminescence (CL) flow-through biosensor for glucose
      was developed by immobilizing glucose oxidase (GOD) and horseradish peroxidase
      (HRP) on the eggshell membrane with glutaraldehyde as a cross-linker. The CL
      detection involved enzymatic oxidation of glucose to D-gluconic acid and hydrogen
      peroxide (H2O2) and then H2O2 oxidizing luminol to produce CL emission in the
      presence of HRP. The immobilization condition (e.g., immobilization time, GOD/HRP
      ratio, glutaraldehyde concentration) was studied in detail. It showed good
      storage stability at 4 degrees C over a 5-month period. The proposed biosensor
      exhibited short response time, high sensitivity, easy operation, and simple
      sensor assembly, and the proposed biosensor was successfully applied to the
      determination of glucose in human serum.

PMID- 18036548
TI  - Detection of the acrolein-derived cyclic DNA adduct by a quantitative 32P
      postlabeling/solid-phase extraction/HPLC method: blocking its artifact formation
      with glutathione.
AB  - Acrolein (Acr), a hazardous air pollutant, reacts readily with deoxyguanosine
      (dG) in DNA to produce cyclic 1, N2-propanodeoxyguanosine adducts (Acr-dG).
      Studies demonstrate that these adducts are detected in vivo and may play a role
      in mutagenesis and carcinogenesis. In the study described here, a quantitative
      32P-postlabeling/solid-phase extraction/HPLC method was developed by optimizing
      the solid-phase extraction and the 32P-postlabeling conditions for analysis of
      Acr-dG in DNA samples with a detection limit of 0.1 fmol. It was found that Acr
      dG can form as an artifact during the assay. Evidence obtained from mass
      spectrometry indicates that the Acr in water used in the assay is a likely source
      of artifact formation of Acr-dG. The formation of Acr-dG as an artifact can be
      effectively blocked by adding glutathione (GSH) to the DNA sample to be analyzed.
      In addition, Acr-dG was detected as a contaminant in the commercial dG and dT 3'
      monophosphate samples. Finally, this method was used to detect Acr-dG in calf
      thymus and human colon HT29 cell DNA with an excellent linear quantitative
      relationship.

PMID- 18036549
TI  - Simultaneous extraction of several metabolites of energy metabolism and related
      substances in mammalian cells: optimization using experimental design.
AB  - As a basis for the development of predictive mathematical models in systems
      biology and a quantitative understanding of cellular metabolism, reliable
      experimental data sets of intracellular metabolites are indispensable. A
      prerequisite for the acquisition of such data is the identification of a suitable
      sample preparation method. In this work, the extraction procedure for the
      simultaneous measurement of a wide range of intracellular metabolites from
      adherent mammalian cells in culture was optimized. A screening of several
      commonly used extraction protocols with Madin-Darby canine kidney (MDCK) cells
      found the methanol/chloroform (MeOH/CHCl(3)) and MeOH/Boil methods to be
      promising candidates for further analysis by anion-exchange chromatography. Both
      methods were optimized based on experimental design techniques with four response
      variables: Nucleotide Content, Energy Charge, Fructose 1,6-Bisphosphate content
      (F16bP), and Absorption at 280 nm. After data evaluation and with the help of
      desirability functions, an overall optimum for the extraction conditions was
      found. Using optimal settings, the extraction performances for MDCK and Vero cell
      cultivations of both methods were compared. Both methods extracted nearly the
      same absolute amounts of intracellular metabolites, suggesting that these methods
      are equal. However, recoveries for nucleotide diphosphates were significantly
      above 100% for both methods. This most likely was due to remaining nucleotide
      kinase activity during extraction. After combining individual steps of both
      methods, recoveries close to 100% for all metabolites could be reached. Absolute
      values of intracellular metabolites extracted with this modified method are
      comparable to the results of the two previously optimized methods, indicating a
      good extraction procedure according to the chosen response variables.

PMID- 18036550
TI  - The polypeptides COX2A and COX2B are essential components of the mitochondrial
      cytochrome c oxidase of Toxoplasma gondii.
AB  - Two genes encoding cytochrome c oxidase subunits, Cox2a and Cox2b, are present in
      the nuclear genomes of apicomplexan parasites and show sequence similarity to
      corresponding genes in chlorophycean algae. We explored the presence of COX2A and
      COX2B subunits in the cytochrome c oxidase of Toxoplasma gondii. Antibodies were
      raised against a synthetic peptide containing a 14-residue fragment of the COX2A
      polypeptide and against a hexa-histidine-tagged recombinant COX2B protein. Two
      distinct immunochemical stainings localized the COX2A and COX2B proteins in the
      parasite's mitochondria. A mitochondria-enriched fraction exhibited cyanide
      sensitive oxygen uptake in the presence of succinate. T. gondii mitochondria were
      solubilized and subjected to Blue Native Electrophoresis followed by second
      dimension electrophoresis. Selected protein spots from the 2D gels were subjected
      to mass spectrometry analysis and polypeptides of mitochondrial complexes III, IV
      and V were identified. Subunits COX2A and COX2B were detected immunochemically
      and found to co-migrate with complex IV; therefore, they are subunits of the
      parasite's cytochrome c oxidase. The apparent molecular mass of the T. gondii
      mature COX2A subunit differs from that of the chlorophycean alga Polytomella sp.
      The data suggest that during its biogenesis, the mitochondrial targeting sequence
      of the apicomplexan COX2A precursor protein may be processed differently than the
      one from its algal counterpart.

PMID- 18036551
TI  - Oxygen sensors in context.
AB  - The ability to adapt to changes in the availability of O2 provides a critical
      advantage to all O2-dependent lifeforms. In mammals it allows optimal matching of
      the O2 requirements of the cells to ventilation and O2 delivery, underpins vital
      changes to the circulation during the transition from fetal to independent, air
      breathing life, and provides a means by which dysfunction can be limited or
      prevented in disease. Certain tissues such as the carotid body, pulmonary
      circulation, neuroepithelial bodies and fetal adrenomedullary chromaffin cells
      are specialised for O2 sensing, though most others show for example alterations
      in transcription of specific genes during hypoxia. A number of mechanisms are
      known to respond to variations in PO2 over the physiological range, and have been
      proposed to fulfil the function as O2 sensors; these include modulation of
      mitochondrial oxidative phosphorylation and a number of O2-dependent synthetic
      and degradation pathways. There is however much debate as to their relative
      importance within and between specific tissues, whether their O2 sensitivity is
      actually appropriate to account for their proposed actions, and in particular
      their modus operandi. This review discusses our current understanding of how
      these mechanisms may operate, and attempts to put them into the context of the
      actual PO2 to which they are likely to be exposed. An important point raised is
      that the overall O2 sensitivity (P50) of any O2-dependent mechanism does not
      necessarily correlate with that of its O2 sensor, as the coupling function
      between the two may be complex and non-linear. In addition, although the bulk of
      the evidence suggests that mitochondria act as the key O2 sensor in carotid body,
      pulmonary artery and chromaffin cells, the signalling mechanisms by which
      alterations in their function are translated into a response appear to differ
      fundamentally, making a global unified theory of O2 sensing unlikely.

PMID- 18036552
TI  - Dynamic aspects of extracellular loop region as a proton release pathway of
      bacteriorhodopsin studied by relaxation time measurements by solid state NMR.
AB  - Local dynamics of interhelical loops in bacteriorhodopsin (bR), the extracellular
      BC, DE and FG, and cytoplasmic AB and CD loops, and helix B were determined on
      the basis of a variety of relaxation parameters for the resolved 13C and 15N
      signals of [1-13C]Tyr-, [15N]Pro- and [1-13C]Val-, [15N]Pro-labeled bR.
      Rotational echo double resonance (REDOR) filter experiments were used to assign
      [1-13C]Val-, [15N]Pro signals to the specific residues in bR. The previous
      assignments of [1-13C]Val-labeled peaks, 172.9 or 171.1 ppm, to Val69 were
      revised: the assignment of peak, 172.1 ppm, to Val69 was made in view of the
      additional information of conformation-dependent 15N chemical shifts of Pro
      bonded to Val in the presence of 13C-15N correlation, although no assignment of
      peak is feasible for 13C nuclei not bonded to Pro. 13C or 15N spin-lattice
      relaxation times (T1), spin-spin relaxation times under the condition of CP-MAS
      (T2), and cross relaxation times (TCH and TNH) for 13C and 15N nuclei and carbon
      or nitrogen-resolved, 1H spin-lattice relaxation times in the rotating flame (1H
      T1 rho) for the assigned signals were measured in [1-13C]Val-, [15N]Pro-bR. It
      turned out that V69-P70 in the BC loop in the extracellular side has a rigid beta
      sheet in spite of longer loop and possesses large amplitude motions as revealed
      from 13C and 15N conformation-dependent chemical shifts and T1, T2, 1H T1 rho and
      cross relaxation times. In addition, breakage of the beta-sheet structure in the
      BC loop was seen in bacterio-opsin (bO) in the absence of retinal.

PMID- 18036553
TI  - A comparative study of mechanisms of surfactant inhibition.
AB  - Pulmonary surfactant spreads to the hydrated air-lung interface and reduces the
      surface tension to a very small value. This function fails in acute respiratory
      distress syndrome (ARDS) and the surface tension stays high. Dysfunction has been
      attributed to competition for the air-lung interface between plasma proteins and
      surfactant or, alternatively, to ARDS-specific alterations of the molecular
      profile of surfactant. Here, we compared the two mechanisms in vitro, to assess
      their potential role in causing respiratory distress. Albumin and fibrinogen
      exposure at or above blood level concentrations served as the models for testing
      competitive adsorption. An elevated level of cholesterol was chosen as a known
      adverse change in the molecular profile of surfactant in ARDS. Bovine lipid
      extract surfactant (BLES) was spread from a small bolus of a concentrated
      suspension (27 mg/ml) to the air-water interface in a captive bubble
      surfactometer (CBS) and the bubble volume was cyclically reduced and increased to
      assess surface activity of the spread material. Concentrations of inhibitors and
      the concentration and spreading method of pulmonary surfactant were chosen in an
      attempt to reproduce the exposure of surfactant to inhibitors in the lung. Under
      these conditions, neither serum albumin nor fibrinogen was persistently
      inhibitory and normal near-zero minimum surface tension values were obtained
      after a small number of cycles. In contrast, inhibition by an increased level of
      cholesterol persisted even after extensive cycling. These results suggest that in
      ARDS, competitive adsorption may not sufficiently explain high surface tension,
      and that disruption of the surfactant film needs to be given causal
      consideration.

PMID- 18036555
TI  - Residues Arg114 and Arg337 are critical for the proper function of Escherichia
      coli gamma-glutamyltranspeptidase.
AB  - To evaluate the importance of conserved Arg114 and Arg337 residues of Escherichia
      coli gamma-glutamyltranspeptidase (EcGGT), Lys, Leu, or Asp-substituted mutants
      were constructed by site-directed mutagenesis. The wild-type and mutant enzymes
      were overexpressed in the recombinant E. coli M15 and purified by nickel-chelate
      chromatography to near homogeneity. With the exception of R114K, all the other
      mutants significantly lost GGT activity, confirming the importance of these two
      residues in EcGGT. Kinetic analysis of R114L, R114D, R337K, and R337L revealed a
      significant increase in K(m) with a minor change in k(cat), leading to more than
      an 8-fold decrease in k(cat)/K(m) values. Mutations of Arg337 impaired the
      capability of autocatalytic processing of the enzyme. In vitro maturation
      experiments revealed that EcGGT precursor mutants, pro-R337K and pro-R337L, could
      precede a time-dependent autocatalytic process to generate the small and large
      subunits, while no autocatalytic processing was observed in pro-R337D. Computer
      modeling showed that the critical bonding distance of Gln390 O-Thr391 HG1 and
      Gln390 C-Thr391 OG1 are significantly increased in Arg337 replacements, implying
      that these distance changes might be responsible for the lack of enzyme
      maturation.

PMID- 18036554
TI  - Association of mitochondrial nitric oxide synthase activity with respiratory
      chain complex I.
AB  - The present study shows that rat liver and brain mitochondrial nitric oxide
      synthase (mtNOS) are functionally associated with mitochondrial respiratory chain
      complex I. When complex I is activated, mtNOS exerts high activity and generates
      nitric oxide, whereas inactivation of complex I leads mtNOS to abandon its NOS
      activity. Functional association of mtNOS with complex I is potentially important
      in regulating mtNOS activity and mitochondrial functions.

PMID- 18036556
TI  - Complementary roles of the DRY motif and C-terminus tail of GPCRS for G protein
      coupling and beta-arrestin interaction.
AB  - beta-arrestin mediates the desensitization of GPCRs and acts as an adaptor
      molecule to recruit the receptor complex to clathrin-rich regions. Class-A GPCRs
      subsequently dissociate from beta-arrestin but class-B GPCRs internalize with
      beta-arrestin in the endocytic vesicles. Here the dopamine D(2) and D(3)
      receptors, which have similar structural features but different intracellular
      trafficking properties, were used in an attempt to better understand the
      structural requirements for the classification of GPCRs. The C-terminus tail of
      the vasopressin type-2 receptor was added to the ends of D(2)R and D(3)R to
      increase their affinity to beta-arrestin. A point mutation was introduced into
      the DRY motif to change their basal activation levels. Among a battery of
      constructs in which the C-terminus tail and/or DRY motif was altered, class-B
      behavior was observed with the constructs whose affinities for beta-arrestin were
      increased complementarily and their signaling was either maintained or regained.
      In conclusion, the DRY motif and C-terminal tail of the GPCRs determine
      complementarily their intracellular trafficking behavior by regulating the
      affinity to beta-arrestin and G protein coupling.

PMID- 18036557
TI  - p53 is important for the anti-proliferative effect of ibuprofen in colon
      carcinoma cells.
AB  - S-ibuprofen which inhibits the cyclooxygenase-1/-2 and R-ibuprofen which shows no
      COX-inhibition at therapeutic concentrations have anti-carcinogenic effects in
      human colon cancer cells; however, the molecular mechanisms for these effects are
      still unknown. Using HCT-116 colon carcinoma cell lines, expressing either the
      wild-type form of p53 (HCT-116 p53(wt)) or being p(HCT-116 p53(-/-)), we
      demonstrated that both induction of a cell cycle block and apoptosis after S- and
      R-ibuprofen treatment is in part dependent on p53. Also in the in vivo nude mice
      model HCT-116 p53(-/-) xenografts were less sensitive for S- and R-ibuprofen
      treatment than HCT-116 p53(wt) cells. Furthermore, results indicate that
      induction of apoptosis in HCT-116 p53(wt) cells after ibuprofen treatment is in
      part dependent on a signalling pathway including the neutrophin receptor
      p75(NTR), p53 and Bax.

PMID- 18036558
TI  - CMT3 alters mitochondrial function in murine osteoclast lineage cells.
AB  - Chemically modified tetracyclines (CMTs 1-10) were developed as non-antibiotic
      inhibitors of matrix metalloproteinases (MMPs). We previously demonstrated that
      MMP inhibition alone is insufficient to explain the pro-apoptotic action of CMTs
      in osteoclast lineage cells and we have explored additional mechanisms of action.
      We compared the characteristics of apoptosis in RAW264.7 murine monocyte and
      osteoclast cultures treated with pharmacologically relevant concentrations of
      CMT3 or the bisphosphonate alendronate, which induces osteoclast apoptosis
      through inhibition of farnesyl diphosphate synthase. CMT3 induced apoptosis
      rapidly (2-3h), whereas alendronate-induced apoptosis was delayed (>12h). CMT3
      treated cells did not accumulate unprenylated Rap1A in contrast to cells treated
      with alendronate. Importantly, CMT3 induced a rapid loss of mitochondrial
      stability in RAW264.7 cells measured by loss of Mitotracker((R)) Red
      fluorescence, while bongkrekic acid protected polykaryons from CMT3-induced
      apoptosis. Modulation of mitochondrial function is therefore a significant early
      action of CMT3 that promotes apoptosis in osteoclast lineage cells.

PMID- 18036559
TI  - Analysis of cotinine in dried blood spots by LC APCI tandem mass spectrometry.

PMID- 18036560
TI  - Relationship between plasma apolipoproteinB concentrations,
      apolipoproteinB/apolipoproeinA-I and HDL subclasses distribution.
AB  - BACKGROUND: To analyze the relationship between plasma apoB100 concentrations,
      apoB100/apoA-I ratio and the alteration of HDL subclasses distribution. METHODS:
      The apoA-I contents of plasma HDL subclasses were quantitated by 2-dimensional
      gel electrophoresis coupled with immunodetection in 506 subjects. RESULTS: The
      subjects in the highest tertile of apoB100 groups had significantly higher small
      sized prebeta(1)-HDL, however lower large-sized HDL(2a), HDL(2b) than the
      subjects in the lowest tertile of apoB100 group. Furthermore, a significant down
      in the HDL(2b)/prebeta(1)-HDL values (from 6.8 to 1.6) with a rise in
      apoB100/apoA-I ratio (from 0.4 to 1.4) were observed. Compared to subjects with
      apoB100/apoA-I ratio<0.9, the subjects with apoB100/apoA-I ratio > or =0.9 had
      significantly higher small-sized prebeta(1)-HDL whereas lower HDL(3a), HDL(3b)
      and large-sized HDL(2a), HDL(2b.) Pearson correlation revealed that
      concentrations of apoB100 were positively correlated with prebeta(1)-HDL but
      negatively correlated with HDL(2a) and HDL(2b), and in multivariate analysis, all
      HDL subclasses were independently associated with the apoB100/apoA-I ratio.
      CONCLUSION: The apoB100 concentrations, especially apoB100/apoA-I ratio could
      reflect sensitively the alteration of HDL subclasses distribution. And HDL
      subclasses distribution characteristics of hyperlipidemic subjects appeared in
      the subjects with apoB100/apoA-I ratio > or =0.9, which indicated the efficiency
      of RCT was weakened and the maturation of HDL was blocked.

PMID- 18036561
TI  - Relation of ischemia-modified albumin levels and left ventricular systolic
      function in patients with ST-segment elevation myocardial infarction treated with
      primary percutaneous coronary intervention.
AB  - BACKGROUND: Ischemia-modified albumin (IMA) has been shown to be elevated in
      patients after percutaneous coronary intervention (PCI). Our goal was to
      investigate the association between IMA levels and left ventricular ejection
      fraction in patients with ST-segment elevation myocardial infarction (STEMI)
      treated with PCI and who developed heart failure during their Coronary Care Unit
      (CCU) stay. METHODS: We assessed 75 patients with a first STEMI. Presence of
      heart failure was assessed during CCU admission, and patients were subdivided
      into 2 groups: group A (n=45) comprised patients in Killip class I, and group B
      (n=30) Killip classes>I. Serum IMA concentration was measured within the first 15
      min post-PCI. The IMA measured was performed using an indirect method based in
      the Albumin Cobalt Binding (ACB) colorimetric assay. The ideal cutoff value of
      IMA was calculated by the receiver operating characteristic (ROC) curve analysis.
      RESULTS: Serum IMA concentrations were significantly higher in group B than in
      group A (0.37+/-0.09 vs 0.30+/-0.06 (A.U.); p<0.0001). The sensitivity and
      specificity of IMA for heart failure were 93.3% and 37.7%, respectively, at 0.31
      A.U. Multivariable adjustment IMA showed a significant inverse correlation with
      left ventricular ejection function (r=-0.32; p=0.004). On multivariable analysis
      both IMA (OR=2.1, 95%CI: 1.2 to 3.9, p<0.001) and left ventricular ejection
      function (OR=1.7, 95%CI: 1.1 to 2.1, p<0.01) correlated with the occurrence of
      heart failure. CONCLUSION: In patients with STEMI undergoing PCI, serum IMA
      concentrations are significantly related to LVEF and represent an early marker of
      left ventricular dysfunction.

PMID- 18036562
TI  - Capillary immunotyping electrophoresis and high resolution two-dimensional
      electrophoresis for the detection of mu-heavy chain disease.
AB  - Heavy chain disease with monoclonal incomplete mu-heavy chains (mu-HCD) is a rare
      disorder usually associated with an underlying lymphoproliferative malignancy.
      Laboratory diagnosis of patients with mu-HCD is usually challenging and the
      monoclonal protein is not detected by electrophoresis in up to 75% of mu-HCD
      cases. We describe a patient with multiple malignancies in whom we detected and
      characterized monoclonal mu-heavy chains using immunofixation electrophoresis,
      capillary zone electrophoresis with immunotyping, and high resolution two
      dimensional electrophoresis. The high resolution 2D electrophoresis enabled us to
      determine the molecular weight of the mu-heavy chains. The abnormal protein
      concentration in the serum was unusually high, 38 g/l measured in our patient is
      the highest reported value in the literature so far.

PMID- 18036563
TI  - Heparin chromatography to deplete high-abundance proteins for serum proteomics.
AB  - BACKGROUND: Serum is a very informative sample for disease diagnosis. However, a
      few of the high-abundance proteins existing in serum make the identification of
      disease-specific serum biomarkers extremely challenging using currently available
      technologies. A highly promising first step for most analytical approaches of
      serum is to deplete as many of the high-abundance proteins as possible. METHODS:
      We introduced the traditional method of heparin chromatography coupled with
      protein G sepharose to deplete the high-abundance proteins for serum proteomics.
      RESULTS: Compared with the multiple affinity removal system (MARS) column (a
      commercial version to deplete 6 major proteins in serum), heparin chromatography
      can deplete more high-abundance proteins in a single step, especially many high
      molecular-weight proteins. Using this simple and inexpensive method to pretreat
      serum for 2-DE analysis, more protein spots can be visualized. IgGs depletion by
      protein G sepharose can further enhance the resolution of the resulting serum
      proteome. CONCLUSIONS: Heparin chromatography coupled with protein G appears to
      be an efficient and economical strategy to pretreat serum for serum proteomics.

PMID- 18036564
TI  - Intrinsic selectivity in binding of matrix metalloproteinase-7 to differently
      charged lipid membranes.
AB  - We provide evidence that matrix metalloproteinase-7 (MMP-7) interacts with
      anionic, cationic and neutral lipid membranes, although it interacts strongest
      with anionic membranes. While the catalytic activity of the enzyme remains
      unaffected upon binding to neutral and negatively charged membranes, it is
      drastically impaired upon binding to the positively charged membranes. The
      structural data reveal that the origin of these features lies in the "bipolar"
      distribution of the electrostatic surface potentials on the crystallographic
      structure of MMP-7.

PMID- 18036565
TI  - Phosphatidic acid plays a special role in stabilizing and folding of the
      tetrameric potassium channel KcsA.
AB  - In this study, we investigated how the presence of anionic lipids influenced the
      stability and folding properties of the potassium channel KcsA. By using a
      combination of gel electrophoresis, tryptophan fluorescence and acrylamide
      quenching experiments, we found that the presence of the anionic lipid
      phosphatidylglycerol (PG) in a phosphatidylcholine (PC) bilayer slightly
      stabilized the tetramer and protected it from trifluoroethanol-induced
      dissociation. Surprisingly, the presence of phosphatidic acid (PA) had a much
      larger effect on the stability of KcsA and this lipid, in addition, significantly
      influenced the folding properties of the protein. The data indicate that PA
      creates some specificity over PG, and that it most likely stabilizes the tetramer
      via both electrostatic and hydrogen bond interactions.

PMID- 18036566
TI  - PPAR delta as a therapeutic target in metabolic disease.
AB  - PPAR delta is the only member in the PPAR subfamily of nuclear receptors that is
      not a target of current drugs. Animal studies demonstrate PPAR delta activation
      exerts many favorable effects, including reducing weight gain, increasing
      skeletal muscle metabolic rate and endurance, improving insulin sensitivity and
      cardiovascular function and suppressing atherogenic inflammation. These
      activities stem largely from the ability of PPAR delta to control energy balance,
      reduce fat burden and protect against lipotoxicity caused by ectopic lipid
      deposition. Therefore, PPAR delta represents a novel therapeutic target and the
      development of PPAR delta gonists/modulators may be useful for treating the whole
      spectrum of metabolic syndrome.

PMID- 18036567
TI  - N-glycan of ErbB family plays a crucial role in dimer formation and tumor
      promotion.
AB  - More and more evidence indicates that N-glycan regulates signal transduction by
      modulating receptor functions. Previous studies suggested that glycosylation of
      EGFR is involved in dimerization and endocytosis. We further determined the role
      of N-glycosylation of ErbB family. A series of human ErbB3 mutants that lack each
      of the 10 N-glycosylation sites were prepared and transfected to Flp-In-CHO cells
      for stable expression. A crosslinking study showed that Asn 418 to Gln mutant
      (N418Q) of ErbB3 underwent autodimerization without its ligand, heregulin, and
      the heterodimer formation with ErbB2 was also increased. The N418Q mutant of
      ErbB3 co-expressed with ErbB2 promoted downstream signaling, anchorage
      independent cell growth and the tumor growth in athymic mice. These findings
      suggest that the specific N-glycan in domain III of ErbB family plays an
      essential role in regulating receptor dimerization and transforming activity. We
      assume that the N-glycans affect the conformation of ErbB family, which is
      crucial for their activity. Together with findings from other laboratories, it is
      suggested that N-glycosylation controls ErbB signaling by various mechanisms.

PMID- 18036568
TI  - Effect of lipid mimetics of GM3 and lyso-GM3 dimer on EGF receptor tyrosine
      kinase and EGF-induced signal transduction.
AB  - The tyrosine kinase activity associated with epidermal growth factor receptor
      (EGFR) has been a target in studies of pharmacological reagents to inhibit growth
      of cancer cells, which are mostly of epidermal origin. Lyso-GM3 dimer showed
      stronger inhibitory effect on the tyrosine kinase of EGFR than GM3, with minimal
      cytotoxicity [Y. Murozuka, et al. Lyso-GM3, its dimer, and multimer: their
      synthesis, and their effect on epidermal growth factor-induced receptor tyrosine
      kinase. Glycoconj. J. 24 (2007) 551-563]. Synthesis of lipids with sphingosine
      requires many steps, and the yield is low. A biocombinatory approach overcame
      this difficulty; however, products required a C(12) aliphatic chain, rather than
      the sphingosine head group [Y. Murozuka, et al. Efficient sialylation on
      azidododecyl lactosides by using B16 melanoma cells. Chemistry & Biodiversity 2
      (2005) 1063-1078]. The present study was to clarify the effects of these lipid
      mimetics of GM3 and lyso-GM3 dimer on EGFR tyrosine kinase activity, and
      consequent changes of the A431 cell phenotype, as follows. (i) A lipid mimetic of
      lyso-GM3 dimer showed similar strong inhibitory effect on EGF-induced EGFR
      tyrosine kinase activity, and similar low cytotoxicity, as the authentic lyso-GM3
      dimer. (ii) A lipid mimetic of lyso-GM3 dimer inhibited tyrosine phosphorylation
      of EGFR or its dimer to a level similar to that of the authentic lyso-GM3 dimer,
      but more strongly than GM3 or a lipid mimetic of GM3. (iii) Associated with the
      inhibitory effect of a lipid mimetic of lyso-GM3 dimer on EGF-induced EGFR kinase
      activity, only Akt kinase activity was significantly inhibited, but kinases
      associated with other signal transducers were not affected. (iv) The cell cycle
      of A431 cells, and the effects of GM3 and a lipid mimetic of lyso-GM3 dimer, were
      studied by flow cytometry, measuring the rate of DNA synthesis with propidium
      iodide. Fetal bovine serum greatly enhanced S phase and G(2)/M phase. Enhanced
      G(2)/M phase was selectively inhibited by pre-incubation of A431 cells with a
      lipid mimetic of lyso-GM3 dimer, whereas GM3 had only a minimal effect.

PMID- 18036569
TI  - Mitochondrial GSH transport and intestinal cell injury: a commentary on
      "Contribution of mitochondrial GSH transport to matrix GSH status and colonic
      epithelial cell apoptosis".

PMID- 18036570
TI  - Anti-inflammatory effects of HO-1 activity in vascular endothelial cells,
      commentary on "Carbon monoxide donors or heme oxygenase (HO-1) overexpression
      blocks interleukin-18-mediated NF-kappaB-PTEN-dependent human cardiac endothelial
      cell death".
AB  - In this issue of Free Radical Biology & Medicine, Zabalgoitia et al. show that IL
      18-dependent cell death of human microvascular endothelial cells (EC) is due to
      activation of p38alpha and NF-kappaB and suppression of p38beta activity. Most
      interestingly, IL-18 and heme oxygenase-1 (HO-1) activities appear to oppose each
      other in these cells. IL-18 suppresses HO-1, an effect that is mediated by
      instability of the HO-1 mRNA. Though the contribution of HO-1 metabolites remains
      somewhat a mystery, treatment with carbon monoxide releasing molecules (CORMs)
      also induces these same effects, implicating carbon monoxide (CO) as a major
      player. HO-1 and CO act to suppress IL-18-mediated activation of p38alpha and to
      restore p38beta activity, which is suppressed by IL-18. Furthermore, HO-1 and CO
      suppress NF-kappaB activation by IL-18. This suppression of NF-kappaB reduces
      levels of PTEN which relieves IL-18-mediated suppression of Akt activity. Thus,
      HO-1 and CO oppose multiple proinflammatory and pro-cell death effects of IL-18
      in human microvascular endothelial cells. The results of this study imply that
      induction of HO-1 or application of CORMs should be protective to the
      microvascular endothelium. Clinical trials to test the effects of CORMs in
      pulmonary inflammation are ongoing. The study by Zabalgoitia et al. provides
      mechanistic information pertaining to the homeostatic balance of IL-18 and HO-1
      activities and may be useful for designing new clinical studies and for
      interpretation of data from ongoing studies.

PMID- 18036571
TI  - Understanding protein folding: small proteins in silico.
AB  - Recent improvements in methodology and increased computer power now allow
      atomistic computer simulations of protein folding. We briefly review several
      advanced Monte Carlo algorithms that have contributed to this development.
      Details of folding simulations of three designed mini proteins are shown. Adding
      global translations and rotations has allowed us to handle multiple chains and to
      simulate the aggregation of six beta-amyloid fragments. In a different line of
      research we have developed several algorithms to predict local features from
      sequence. In an outlook we sketch how such biasing could extend the application
      spectrum of Monte Carlo simulations to structure prediction of larger proteins.

PMID- 18036572
TI  - 4'-methoxy-2-styrylchromone a novel microtubule-stabilizing antimitotic agent.
AB  - 4'-methoxy-2-styrylchromone, a new synthetic chromone was identified as a
      selective proliferation inhibitor of human tumor (MCF-7 and NCI-H460) cell lines
      than to non-tumor cells (MRC-5). The antiproliferative activity of this chromone
      was also extensive to peripheral human lymphocytes. 4'-Methoxy-2-styrylchromone
      was found to block tumor cells in the G2/M phase of the cell cycle. The G2/M
      arrest of NCI-H460 cells was dose- and time-dependent, reaching a maximum after
      12-h treatment while MCF-7 cells reached the maximum value of G2/M accumulation
      only after a 24-h treatment. Chromone-treated cells evidenced a high frequency of
      cells in prometaphase, indicating progression beyond G2 and arrest early in
      mitosis. This mitotic arrest was associated with abnormal mitotic spindles
      characterized by the formation of a monopolar structure, suggesting that the
      chromone interferes with microtubules. The results of an in vitro tubulin
      polymerization assay showed that this chromone stabilizes microtubules in a
      manner similar to paclitaxel.

PMID- 18036573
TI  - The pathogenesis of ethanol versus methionine and choline deficient diet-induced
      liver injury.
AB  - The differences and similarities of the pathogenesis of alcoholic (ASH) and non
      alcoholic steatohepatitis (NASH) were examined. Mice (six/group) received one of
      four Lieber-Decarli liquid diets for 6 weeks: (1) paired-fed control diet; (2)
      control diet with ethanol (ethanol); (3) paired-fed methionine/choline deficient
      (MCD) diet; and (4) MCD plus ethanol (combination). Hepatotoxicity, histology,
      and gene expression changes were examined. Both MCD and ethanol induced
      macrovesicular steatosis. However, the combination diet produced massive
      steatosis with minor necrosis and inflammation. MCD and combination diets, but
      not ethanol, induced serum ALT levels by 1.6- and 10-fold, respectively. MCD
      diet, but not ethanol, also induced serum alkaline phosphatase levels suggesting
      bile duct injury. Ethanol increased liver fatty acid binding protein (L-FABP)
      mRNA and protein levels. In contrast, the combination diet decreased L-FABP mRNA
      and protein levels and increased hepatic free fatty acid and lipid peroxide
      levels. Ethanol, but not MCD, reduced hepatic S-adenosylmethionine (SAM) and GSH
      levels. Hepatic TNFalpha protein levels were increased in all treatment groups,
      however, IL-6, a hepatoprotective cytokine which promotes liver regeneration was
      increased in ethanol-fed mice (2-fold), but decreased in the combination diet
      treated mice. In addition, the combination diet reduced phosphorylated STAT3 and
      Bcl-2 levels. While MCD diet might cause bile duct injury and cholestasis,
      ethanol preferentially interferes with the SAM-GSH oxidative stress pathway. The
      exacerbated liver injury induced by the combination diet might be explained by
      reduced L-FABP, increased free fatty acids, oxidative stress, and decreased IL-6
      protein levels. The combination diet is an efficient model of steatohepatitis.

PMID- 18036574
TI  - In hamsters the D1 receptor antagonist SCH23390 depresses ventilation during
      hypoxia.
AB  - During exposure of animals to hypoxia, brain and blood dopamine levels increase
      stimulating dopaminergic receptors which influence the integrated ventilatory
      response to low oxygen. The purpose of the present study is to test the
      hypothesis that in conscious hamsters, systemic antagonism of D(1) receptors
      would depress their breathing in air and in response to hypoxic and hypercapnic
      challenges. Nine male hamsters were treated with saline or 0.25 mg/kg SCH-23390
      (SCH), a D(1) receptor antagonist that crosses the blood-brain barrier.
      Ventilation was determined using the barometric method, and oxygen consumption
      and CO(2) production were evaluated utilizing the flow-through method. During
      exposure to air, SCH decreased frequency of breathing. During exposure to hypoxia
      (10% oxygen in nitrogen), relative to saline, SCH-treated hamsters decreased
      minute ventilation by decreasing tidal volume and oxygen consumption but not
      CO(2) production. During exposure to hypercapnia (5% CO(2) in 95% O(2)),
      frequency of breathing was decreased with SCH, but there was no significant
      effect on minute ventilation. Relative to saline treatment body temperature was
      lower in SCH-treated hamsters by 0.6 degrees C. These results demonstrate that in
      hamsters D(1) receptors can modulate control of ventilation in air and during
      hypoxia and hypercapnic exposures. Whether D(1) receptors located centrally or on
      carotid bodies modulate these effects is not clear from this study.

PMID- 18036575
TI  - Organization of last-order premotor interneurons related to the protraction of
      tongue in the frog, Rana esculenta.
AB  - Moving visual stimuli elicit a sequence of coordinated activity of muscles
      including tongue protraction. Morphological and physiological studies fail to
      reveal any direct tectal projections to hypoglossal motoneurons suggesting that
      the last-order premotor interneurons (LOPI) are the direct recipients of neural
      activities generated in the optic tectum. The aim of this study is to analyze the
      topographical organization of the last-order premotor interneurons related to
      protractor muscles of the tongue. In Rana esculenta, biotinylated dextran amine
      (BDA) was injected by iontophoresis into the subnucleus of the hypoglossal nerve
      containing the motoneurons of protractor muscles of the tongue. For visualizing
      BDA, sections were treated with avidin-biotin complex and a nickel-enhanced DAB
      chromogen reaction. The position of labeled neurons was reconstructed with a
      Neurolucida equipment. Morphologically heterogeneous populations of neurons were
      detected bilaterally, the majority of them were distributed ipsilateral to the
      site of injection and extended 1200 microm in rostral and 500 microm in caudal
      directions. Labeled neurons were found in the rhombencephalic reticular
      formation, the vestibular nuclei, the nucleus prepositus hypoglossi, the nucleus
      of solitary tract, the spinal nucleus of trigeminal nerve and the dorsal column
      nuclei. Our results indicate that the majority of last-order premotor
      interneurons related to protractor muscles of the tongue are located in the
      reticular formation of the brainstem. Since this area also receives a significant
      input from the vestibular system and from proprioceptive fibers, the last-order
      premotor interneurons presented here may be the target of convergence of sensory
      modalities involved in prey-catching behavior.

PMID- 18036577
TI  - Human EEG very high frequency oscillations reflect the number of matches with a
      template in auditory short-term memory.
AB  - Auditory perception comprises bottom-up as well as top-down processes. While
      research in the past has revealed many neural correlates of bottom-up processes,
      less is known about top-down modulation. Memory processes have recently been
      associated with oscillations in the gamma-band of human EEG (30 Hz and above)
      which are enhanced when incoming information matches a stored memory template.
      Therefore, we investigated event-related potentials (ERPs) and gamma-band
      activity in 17 healthy participants in a Go/NoGo-task. They listened to four
      frequency-modulated (FM) sounds which varied regarding the frequency range
      traversed and the direction of frequency modulation. One sound was defined as
      target and required a button press. The results of ERPs (N1, P2, N2, and P3) were
      consistent with previous studies. Analysis of evoked gamma-band responses yielded
      no significant task-dependent modulation, but we observed a stimulus dependency,
      which was also present in a control experiment: The amplitude of evoked gamma
      responses showed an inverted U-shape as a function of stimulus frequency.
      Investigation of total gamma activity revealed functionally relevant responses at
      high frequencies (90 Hz to 250 Hz), which showed significant modulations by
      matches with STM: Complete matches led to the strongest enhancements (starting
      around 100 ms after stimulus onset) and partial matches resulted in intermediate
      ones. The results support the conclusion that very high frequency oscillations
      (VHFOs) are markers of active stimulus discrimination in STM matching processes
      and are attributable to higher cognitive functions.

PMID- 18036576
TI  - Interleukin-1beta interferes with signal transduction induced by neurotrophin-3
      in cortical neurons.
AB  - It was previously observed that IL-1beta interferes with BDNF-induced TrkB
      mediated signal transduction and protection of cortical neurons from apoptosis
      evoked by deprivation from trophic support [Tong L., Balazs R., Soiampornkul R.,
      Thangnipon W., Cotman C.W., 2007. Interleukin-1beta impairs brain derived
      neurotrophic factor-induced signal transduction. Neurobiol. Aging]. Here we
      investigated whether the effect of the cytokine on neurotrophin signaling is more
      general. The influence of IL-1beta on NT-3 signaling was therefore studied under
      conditions when NT-3 primarily activated the TrkC receptor. The cytokine reduced
      NT-3-induced activation of MAPK/ERK and Akt, but did not interfere with Trk
      receptor autophosphorylation. IL-1beta reduced tyrosine phosphorylation of the
      docking proteins, IRS-1 and Shc, which convey receptor activation to the
      downstream protein kinase cascades. These are the steps that are also inhibited
      by IL-1beta in BDNF-induced signal transduction. The functional consequences of
      the effect of IL-1beta on NT-3 signaling were severe, as NT-3 protection of the
      trophic support-deprived cortical neurons was abrogated. In view of the role in
      the maintenance and plasticity of neurons of ERK, Akt and CREB, which are
      activated by neurotrophins, elevated IL-1beta levels in the brain in Alzheimer's
      disease and other neurodegenerative diseases might contribute to the decline in
      cognitive functions before the pathological signs of the disease develop.

PMID- 18036578
TI  - Expression of MAP/ERK kinase cascade corresponds to the ability to develop food
      aversion in terrestrial snail at different stages of ontogenesis.
AB  - The mitogen-activated protein kinase/extracellular signal-regulated kinase
      (MAPK/ERK) cascade plays an important role in gene expression regulation during
      memory formation in both vertebrates and invertebrates. MAPK/ERK regulates gene
      expression through phosphorylation of transcription factors binding to the
      regulatory elements SRE and CRE of target genes. Previously we reported that
      juvenile snails Helix lucorum differ from adult animals in a spectrum of
      transcription factors binding to DNA regulatory elements SRE and AP-1. In this
      study we analyzed the expression and activation of MAPK/ERK in CNS of H. lucorum
      during formation of the conditioned avoidance reflex at different stages of
      postnatal ontogenesis. Under conditions of learning, juvenile snails (aged 2-3
      months) possessing immature mechanisms of avoidance reflex plasticity showed
      dramatically low level of phosphorylation and, correspondingly, low activation of
      MAPK/ERK in comparison to adult animals. Beside this, the MAPK/ERK cascade was
      not activated after 10 and 60 min after learning in juvenile snails in contrast
      to adults, while basal expression level of this kinase was similar in juveniles
      and adults. Low activation of MAPK/ERK cascade can cause a deficiency in
      phosphorylation of downstream transcription factors binding to SRE and thereby
      influence the expression of early response genes (particularly, of the family AP
      1) and late response genes necessary for cellular and synaptic plasticity. These
      observations suggest that the MAPK/ERK regulatory cascade plays an essential role
      in the formation of conditioned avoidance reflexes in Helix. Low activation of
      this cascade might be one of the reasons for deficiency of long-term memory
      formation during avoidance learning in juvenile animals.

PMID- 18036579
TI  - QA aspects for HbA1c measurements.
AB  - OBJECTIVES: To provide mechanisms for evaluating HbA(1c) results that meet the
      criteria for review by the 2002 NACB guidelines for reporting HbA(1c) values.
      DESIGN AND METHODS: Complete blood count (CBC) data and comparison of obtained
      HbA(1c) with a calculated HbA(1c) were used to assess the validity of HbA(1c)
      results meeting the NACB review criteria. RESULTS: The use of CBC data and a
      calculated HbA(1c) were found to be useful in evaluating the validity of unusual
      HbA(1c) results. CONCLUSIONS: The validity of high and low HbA(1c) results can be
      checked by the review of CBC data and comparing a calculated HbA(1c) against the
      measured value.

PMID- 18036581
TI  - Stem-loop binding protein expressed in growing oocytes is required for
      accumulation of mRNAs encoding histones H3 and H4 and for early embryonic
      development in the mouse.
AB  - Growing oocytes accumulate mRNAs and proteins that support early embryogenesis.
      Among the most abundant of these maternal factors are the histones. Histone mRNA
      accumulation and translation are mainly restricted to S-phase in somatic cells,
      and the mechanism by which oocytes produce histones is unknown. In somatic cells,
      replication-dependent histone synthesis requires the stem-loop binding protein
      (SLBP). SLBP is expressed during S-phase, binds to the 3'-untranslated region of
      non-polyadenylated transcripts encoding the histones, and is required for their
      stabilization and translation. SLBP is expressed in oocytes of several species,
      suggesting a role in histone synthesis. To test this, we generated transgenic
      mice whose oocytes lack SLBP. mRNAs encoding histones H3 and H4 failed to
      accumulate in these oocytes. Unexpectedly, mRNAs encoding H2A and H2B were little
      affected. Embryos derived from SLBP-depleted oocytes reached the 2-cell stage,
      but most then became arrested. Histones H3 and H4, but not H2A or H2B, were
      substantially reduced in these embryos. The embryos also expressed high levels of
      gamma H2A.X. Injection of histones into SLBP-depleted embryos rescued them from
      developmental arrest. Thus, SLBP is an essential component of the mechanism by
      which growing oocytes of the mouse accumulate the histones that support early
      embryonic development.

PMID- 18036580
TI  - Disruption of the PACAP gene promotes medulloblastoma in ptc1 mutant mice.
AB  - Hedgehog (Hh) proteins and cAMP-dependent protein kinase A (PKA) generally play
      opposing roles in developmental patterning events. Humans and mice heterozygous
      for mutations in the sonic hedgehog (Shh) receptor gene patched-1 (ptc1) have an
      increased incidence of certain types of cancer, including medulloblastoma (MB), a
      highly aggressive tumor of the cerebellum. Despite the importance of PKA in Hh
      signaling, little is known about how PKA activity is regulated in the context of
      Hh signaling, or the consequences of improper regulation. One molecule that can
      influence PKA activity is pituitary adenylyl cyclase-activating peptide (PACAP),
      which has been shown to regulate cerebellar granule precursor proliferation in
      vitro, a cell population thought to give rise to MB. To test for a PACAP/Hh
      interaction in the initiation or propagation of these tumors, we introduced a
      PACAP mutation into ptc1 mutant mice. Deletion of a single copy of PACAP
      increased MB incidence approximate 2.5-fold, to 66%, thereby demonstrating that
      PACAP exerts a powerful inhibitory action on the induction, growth or survival of
      these tumors. Tumors from PACAP/ptc1 mutant mice retained PACAP receptor gene
      expression, and exhibited superinduction of Hh target genes compared to those
      from ptc1+/- mice. Moreover, PACAP inhibited proliferation of cell lines derived
      from tumors in a PKA-dependent manner, and inhibited expression of the Hh target
      gene gli1. The results provide genetic evidence that PACAP acts as a
      physiological factor that regulates the pathogenesis of Hh pathway-associated MB
      tumors.

PMID- 18036582
TI  - Dorsoventral patterning of the C. elegans postembryonic mesoderm requires both
      LIN-12/Notch and TGFbeta signaling.
AB  - The C. elegans postembryonic mesodermal lineage arises from a single cell M,
      which generates distinct dorsal and ventral cell types. We have previously shown
      that mutations in the Schnurri homolog sma-9 cause ventralization of the M
      lineage and that wild-type SMA-9 antagonizes the Sma/Mab TGFbeta pathway to
      promote dorsal M lineage fates [Foehr, M.L., Lindy, A.S., Fairbank, R.C., Amin,
      N.M., Xu, M., Yanowitz, J., Fire, A.Z., Liu, J., 2006. An antagonistic role for
      the C. elegans Schnurri homolog SMA-9 in modulating TGFbeta signaling during
      mesodermal patterning. Development 133, 2887-2896]. Interestingly, loss-of
      function mutations in the Notch receptor lin-12 cause dorsalization of the M
      lineage [Greenwald, I.S., Sternberg, P.W., Horvitz, H.R., 1983. The lin-12 locus
      specifies cell fates in Caenorhabditis elegans. Cell 34, 435-444]. We have found
      that although LIN-12 protein is present in both the dorsal and ventral M lineage
      cells, its ligands LAG-2 and APX-1 are asymmetrically localized in cells adjacent
      to ventral M-derived cells, and may function redundantly in promoting ventral M
      lineage fates. To investigate how LIN-12/Notch signaling interacts with SMA-9 and
      Sma/Mab TGFbeta signaling in regulating M lineage patterning, we generated double
      and triple mutant combinations among lin-12, sma-9 and dbl-1 (the ligand for the
      Sma/Mab TGFbeta pathway) and examined their M lineage phenotypes. Our results
      suggest that the LIN-12/Notch pathway and the Sma/Mab TGFbeta pathway function
      independently in regulating dorsoventral patterning of the M lineage, with LIN
      12/Notch required for ventral M lineage fates, and SMA-9 antagonism of TGFbeta
      signaling required for dorsal M lineage fates. Our work provides a model for how
      combined Notch and TGFbeta signaling regulates the developmental potential of two
      equipotent cells along the dorsoventral axis.

PMID- 18036583
TI  - Behavioural and neurochemical characterization of the adenosine A2A receptor
      antagonist ST1535.
AB  - ST1535 (2-butyl-9-methyl-8-(2H-1,2,3-triazol 2-yl)-9 H-purin-6-ylamine) is a
      novel compound showing a preferential adenosine A(2A) receptor antagonist
      profile. To explore the potential neuroprotective profile of this compound, we
      evaluated whether ST1535 prevented quinolinic acid (QA)-induced glutamate outflow
      in the rat striatum (a reliable index of neuroprotective activity in vivo).
      Microdialysis experiments were performed in naive Wistar rats. In these
      experiments, a behaviourally active and inactive doses of ST1535 were used. Both
      doses significantly prevented QA-induced glutamate outflow in the striatum. These
      results show that ST1535 protects towards striatal excitotoxicity, even though
      its reduced A(2A)/A(1) selectivity might limit its actual neuroprotective
      potential.

PMID- 18036584
TI  - Cardiovascular effects of tyramine: adrenergic and cholinergic interactions.
AB  - The cardiovascular effects of tyramine, and its interactions with propranolol,
      atenolol, phentolamine, prazosin, yohimbine and atropine, have been investigated
      in anesthetized rats in vivo and in vitro. Tyramine (i.v.) increased both the
      mean arterial blood pressure and heart rate. Phentolamine, prazosin or a
      combination of prazosin and yohimbine caused an inhibition of the hypertensive
      effect of tyramine, but propranolol, atenolol and/or atropine had no effect.
      Propranolol added to rats receiving atropine depressed the chronotropic effect of
      tyramine. However, in non-atropinized animals, the positive chronotropic effect
      of tyramine was paradoxically enhanced by propranolol, and further enhanced by
      atropine. A similar result was found with atenolol pre-treated animals.
      Phentolamine did not alter the effects of propranolol and atropine on heart rate.
      Prazosin depressed the positive chronotropic effects of tyramine, and this effect
      was re-stored by pre-treatment of the animals with both prazosin and yohimbine.
      In the isolated atria, propranolol--in contrast to the in vivo results--inhibited
      the chronotropic effect of tyramine. Atropine potentiated the positive inotropic
      effect of isoproterenol and tyramine. Tyramine produced a concentration-dependent
      contraction of isolated thoracic aortic rings, and this was potentiated by N(G)
      nitro-l-arginine, or by removal of the endothelium, but inhibited by
      phentolamine. The in vivo and in vitro effects of tyramine were not seen in rats
      which had been treated with reserpine. We conclude that the positive inotropic
      and chronotropic effects of tyramine in the rat are due to indirect release of
      transmitter. The results suggest that the paradoxical enhancement by propranolol
      and atenolol of the chronotropic effect in vivo could be due to tyramine causing
      increased vagal activity, such that an inhibitory effect of propranolol can only
      be revealed in animals treated with atropine.

PMID- 18036585
TI  - Therapeutic resistance to angiotensin converting enzyme (ACE) inhibition is
      related to pharmacodynamic and -kinetic factors in 5/6 nephrectomized rats.
AB  - Proteinuria plays a pathogenic role in the development of end stage renal
      disease. Angiotensin converting enzyme (ACE) inhibitors lower proteinuria and are
      renoprotective. However, large inter-individual variation in antiproteinuric
      response to ACE inhibitors exists. In this study, we explored the mechanism of
      therapeutic resistance to an ACE inhibitor in the rat 5/6 nephrectomy model. At
      week 6 after 5/6 nephrectomy, treatment with lisinopril was initiated for 6
      weeks. Proteinuria and blood pressure were evaluated weekly. At the end of the
      experiment, rats were divided into tertiles according to their antiproteinuric
      response: (1) responders (n=9), (2) intermediate responders (n=8) and (3) non
      responders to ACE inhibitor therapy (n=9). At the start of treatment, proteinuria
      had progressively increased to 154 (95% confidence interval [CI]: 123-185) mg/24
      h in the entire cohort, with comparable proteinuria and blood pressure in all
      groups. Following treatment with ACE inhibitor, proteinuria was significantly
      lower in the responders (68, CI: 46-89 mg/24 h) compared to the non-responders
      (251, CI: 83-420) mg/24 h). Similarly, blood pressure was reduced in the
      responders, but unaffected in the non-responders. At autopsy, renal ACE activity
      and renal ACE expression were significantly lower in the responders compared to
      the non-responders. Although lisinopril intake was comparable in all animals,
      urinary drug excretion was increased in the non-responders, demonstrating
      increased drug clearance. Average urinary lisinopril excretion was correlated
      with antiproteinuric response (R(2)=0.32, P=0.003). In conclusion, both
      pharmacodynamic and -kinetic factors account for the non-response to lisinopril.
      Whether these can be overcome simply by increasing drug dosage in non-responders
      should be investigated.

PMID- 18036586
TI  - Differential effects of the sodium calcium exchange inhibitor, KB-R7943, on
      ischemia and reperfusion injury in isolated guinea pig ventricular myocytes.
AB  - Effects of the Na(+)-Ca(2+) exchange (NCX) inhibitor KB-R7943 on electrical and
      contractile function were examined in guinea pig ventricular myocytes exposed to
      ischemia and reperfusion. Action potentials and transmembrane currents were
      recorded with microelectrodes; contractions were measured with an edge detector.
      Cells were exposed to simulated ischemia (hypoxia, hypercapnia, hyperkalemia,
      acidosis, lactate accumulation, no glucose) for 20 min and reperfused with
      Tyrode's solution. Experiments were conducted at 37 degrees C in the absence or
      presence of KB-R7943. Low concentrations of KB-R7943 (0.1 microM) had little
      impact on changes in contractions, membrane potential, or Ca(2+) current induced
      by ischemia and reperfusion. However, higher concentrations of KB-R7943 (0.5 and
      1.0 microM) reduced the magnitude of Ca(2+) current and promoted action potential
      abbreviation in both ischemia and reperfusion. High concentrations of KB-R7943
      also promoted post-ischemic contractile dysfunction (stunning) in reperfusion. In
      the absence of KB-R7943, the arrhythmogenic transient inward current (I(TI)) plus
      aftercontractions occurred upon reperfusion, and some cells exhibited
      irreversible cell injury (hypercontracture). Higher concentrations of KB-R7943
      (0.5 and 1.0 micoM) did not affect the occurrence or magnitude of I(TI) and
      aftercontractions and did not affect the occurrence of hypercontracture. In
      contrast, 0.1 microM KB-R7943 virtually abolished I(TI), aftercontractions and
      hypercontracture. Thus, low concentrations of KB-R7943 protected against ischemia
      and reperfusion injury, but higher concentrations of drug actually exacerbated
      detrimental effects of ischemia and reperfusion. These results suggest that
      inhibition of I(TI) may contribute to the antiarrhythmic effects of KB-R7943 on
      reperfusion-induced arrhythmias.

PMID- 18036587
TI  - MEN16132, a kinin B2 receptor antagonist, prevents the endogenous bradykinin
      effects in guinea-pig airways.
AB  - Kinins have been suggested to be involved in human airway diseases such as asthma
      and rhinitis. MEN16132 is a non-peptide kinin B(2) receptor antagonist able to
      inhibit the responses produced by intravenous bradykinin into the airways, as
      bronchoconstriction and microvascular leakage; we tested the effect of MEN16132
      on endogenously generated bradykinin through the dextran sulfate-induced contact
      activation of kinin-kallikrein cascade in guinea-pigs. After dextran sulfate
      administration (1.5 mg/kg i.v.), the pulmonary insufflation pressure was
      monitored and the microvascular leakage of upper and lower airways was assessed
      using Evans blue as tracer of plasma protein extravasation. Our results
      demonstrated that topical MEN16132 strongly inhibited the dextran sulfate-induced
      bronchoconstriction (0.3 mM solution aerosol for 5 min) and plasma protein
      extravasation in both lower airways (3-10 microM solution aerosol for 5 min) and
      nasal mucosa (0.3 nmol/nostril); Icatibant, the peptide antagonist of kinin B(2)
      receptor, exerted a 3-30-fold less potent inhibitory effect than MEN16132. We
      conclude that local application of MEN16132 into the airways abolishes the
      responses produced by the endogenous generation of bradykinin and it can be
      useful as new pharmacological tool to check the role of kinins in human diseases.

PMID- 18036589
TI  - Suppressive effects of leflunomide on leptin-induced TIMP-1 production involves
      on hepatic stellate cell proliferation and apoptosis.
AB  - This manuscript revealed that following a fibrogenic stimulus of leptin in vitro,
      hepatic stellate cells (HSCs) underwent a complex activation process
      characterized by increased proliferation and excessive tissue inhibitor of
      metalloproteinase-1 (TIMP-1) production. Studies with special chemical inhibitors
      demonstrated that this process involved Janus protein tyrosine kinase
      (JAK)/signal transducer and activator of transcription (STAT), mitogen-activated
      protein kinases (MAPK), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B
      (Akt) signal pathways. Pretreatment with A771726 (alpha,alpha,alpha-Trifluoro-5
      methyl-4-isoxazolecarboxy-p-toluidide), leflunomide's metabolite, fully prevented
      leptin-induced TIMP-1 production in HSCs. This effect was associated with its
      suppression on HSC proliferation and induction of HSC apoptosis.

PMID- 18036590
TI  - Sulfated glucosamine inhibits oxidation of biomolecules in cells via a mechanism
      involving intracellular free radical scavenging.
AB  - Although, several effects of glucosamine and its sulfated form (sulfated
      glucosamine) have been proposed for the suppression of osteoarthritis, their
      exact mechanisms have not been completely elucidated. This study explains the
      novel possibility of involvement of sulfated glucosamine in improving cellular
      antioxidant potential and thereby controlling oxidative damage that could be
      effective for its therapeutic potential in osteoarthritis. Treatment with
      sulfated glucosamine to human chondrocytes and macrophages inhibited radical
      simulated oxidation of membrane lipids, proteins and DNA in a dose-dependent
      manner. Moreover, detection of reactive oxygen species by electron spin resonance
      (ESR) spectroscopy and 2',7'-dichlorodihydrofluororescein diacetate (DCFH-DA)
      fluorescence probe clearly confirmed effective radical scavenging potential of
      sulfated glucosamine in cellular and non-cellular systems. More importantly, NF
      kappaB reporter gene assay and western blot analysis revealed that sulfated
      glucosamine inhibits radical mediated expression and activation of nuclear factor
      kappaB (NF-kappaB) proteins (transcription factor involves in expression of a
      number of genes related to osteoarthritis). Further, sulfated glucosamine
      enhanced reduced glutathione (GSH) level in oxidatively stressed human
      chondrocytes improving cellular redox balance. In conclusion, it is suggested
      that potential effects of sulfated glucosamine in controlling osteoarthritis
      might be partly via mechanisms involving direct scavenging of cellular radical
      species and alteration of oxidation mediated destructive events.

PMID- 18036588
TI  - Bi-phasic intensity-dependent opioid-mediated neural amplitude changes in the
      chinchilla cochlea: partial blockade by an N-Methyl-D-Aspartate (NMDA)-receptor
      antagonist.
AB  - Dynorphins, glutamate, and glutamate-sensitive N-Methyl-D-Aspartate (NMDA)
      receptors exist in the mammalian cochlea. Dynorphins produce neural excitation
      and excitotoxic effects in the spinal cord through a kappa-opioid facilitation of
      NMDA receptor-sensitivity to glutamate. The kappa-opioid receptor drug agonists N
      dimethylallyl-normetazocine [(-)-pentazocine (50 mmol)] and trans-3,4-dichloro-N
      methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide [U-50488H (100 mmol)]
      were administered across the cochlear round window membrane in the chinchilla.
      Each drug produced significant post-baseline amplitude changes in the click
      evoked auditory nerve compound action potential. Amplitude changes at threshold
      amounted to increases in sensitivity that ranged from 4-8 decibels, measured in
      sound pressure level (dB SPL). The large neural amplitude increases at threshold
      were accompanied by progressively smaller amplitude changes at 5 and 10 dB above
      threshold (dB SL). However, at stimulus intensities > or =20 dB SL, post-baseline
      neural amplitudes were suppressed to levels below baseline and control values.
      These bi-phasic intensity-dependent neural amplitude changes have never before
      been observed following i.v. administered (-)-pentazocine in this species.
      Finally, the bi-phasic neural amplitude changes in U-50488H-treated (100 mmol)
      animals were partially blocked (except at 20 dB SL), following a round window pre
      treatment with the NMDA receptor drug antagonist, dizocilpine hydrogen maleate
      [(+)-MK-801 (8 mmol)]. Our data suggests that endogenous dynorphins within
      lateral efferent olivocochlear neurons differentially modulate auditory neural
      excitation, possibly through cochlear NMDA receptors and glutamate. The role
      played by lateral efferent opioid neuromodulation at cochlear NMDA receptors, is
      discussed.

PMID- 18036591
TI  - Tropomyosin 4 regulates adhesion structures and resorptive capacity in
      osteoclasts.
AB  - Tropomyosins (Tms) are alpha-helical dimers that bind and stabilize actin
      microfilaments while regulating their accessibility to other actin-associated
      proteins. Four genes encode expression of over forty Tms, most of which are
      expressed in nonmuscle cells. In recent years, it has become clear that
      individual Tm isoforms may regulate specific actin pools within cells. In this
      study, we examined how osteoclast function may be regulated by the tropomyosin
      isoform Tm-4, which we previously showed to be highly localized to podosomes and
      sealing zones of osteoclasts. RNAi-mediated knockdown of Tm-4, both in RAW264.7-
      and mouse marrow-derived osteoclasts, resulted in thinning of the actin ring of
      the sealing zone. Knockdown of Tm-4 also resulted in diminished bone resorptive
      capacity and altered resorption pit shape. In contrast, osteoclasts
      overexpressing Tm-4 demonstrated thickened podosomes on glass as well as
      thickened, aberrant actin structures on bone, and diminished motility and
      resorptive capacity. These results indicate that Tm-4 plays a role in regulating
      adhesion structures of osteoclasts, most likely by stabilizing the actin
      microfilaments present in podosomes and the sealing zone.

PMID- 18036592
TI  - Semenogelins in the human retina: Differences in distribution and content between
      AMD and normal donor tissues.
AB  - The two cellular targets of interest in age-related macular degeneration (AMD)
      are the photoreceptors and the RPE. However, the mechanisms involved in AMD
      pathology are not yet fully understood. In the present report, we extend our
      previous studies on semenogelin proteins (Sgs) in normal human retina and compare
      these with the distribution in retinas from AMD donor eyes. Semenogelins I (SgI)
      and II (SgII) are the major structural protein components of semen coagulum, but
      have been recently found in non-genital tissues as well. Cryo and paraffin
      sections of human retina were processed for both immunofluorescence and DAB
      reaction with a specific antibody. The presence of SgI was analyzed in retina and
      RPE total lysates and SgI was detected by western blot in human retina and RPE.
      The intensity of immunoreactivity was significantly reduced in the AMD eyes. SgI
      is expressed in the normal human retina and in the retina of AMD donor eyes,
      where localization was detected in the photoreceptors and in a few ganglion
      cells. We find the distribution of SgI in the AMD retinas substantially lower
      than observed in normal retina. SgI localization to photoreceptors and the RPE
      suggests a possible function related to the ability of these cells to sequester
      zinc.

PMID- 18036593
TI  - Axotomy-induced dopaminergic neurodegeneration is accompanied with c-Jun
      phosphorylation and activation transcription factor 3 expression.
AB  - Accumulating evidence has shown that both phosphorylated c-Jun (pc-Jun) and
      activating transcription factor 3 (ATF3) were upregulated in a variety of tissue
      injuries and proposed to play an important role in cell death/survival. To
      elucidate the significance and functional role of these immediate-early genes
      during neuronal damage in the central nervous system, we examined temporal and
      spatial profiles of pc-Jun and ATF3 in dopaminergic neurons of the substantia
      nigra (SN) following transection of the medial forebrain bundle (MFB) in adult
      rats. Morphological characteristics of pc-Jun-positive dopaminergic neurons as
      well as microglial reaction in response to the axotomy-induced neurodegeneration
      were also investigated. Following MFB transection, both c-Jun phosphorylation and
      ATF3 were found in the nuclei of tyrosine hydroxylase-immunoreactive (TH-ir)
      neurons of the ipsilateral SN, but not in those of the contralateral SN. In the
      ipsilateral SN, the number of pc-Jun- and ATF3-positive nuclei was increased by 5
      7 days post-lesion, and then progressively decreased probably due to the loss of
      neurons. Retrograde tracing with FluoroGold (FG) in hemi-axotomized rat brain
      demonstrated that none of the intact, unaxotomized (FG-ir) neurons was pc-Jun
      positive, indicating phosphorylation of c-Jun occurs only in axotomized neurons.
      Concomitant co-localization of pc-Jun and ATF3 in the same TH-ir neuron was also
      demonstrated by triple immunofluorescence labeling. Many TH-ir neurons that
      underwent various steps of consecutive neurodegenerative changes retained pc-Jun
      in the condensed or fragmented nuclei. Moreover, numerous activated microglia,
      identified by both phagocytic (ED1) and MHC II (OX6) markers, closely apposed to
      these neurons throughout the entire neurodegenerative process, suggesting that
      they are actively phagocytosing dying neurons. Taken together, these results
      support the idea that pc-Jun and its putative dimeric partner ATF3 may be closely
      participating in axotomy-induced neurodegeneration.

PMID- 18036594
TI  - Disordered pancreatic inflammatory responses and inhibition of fibrosis in CD39
      null mice.
AB  - BACKGROUND & AIMS: Extracellular nucleotides are released from injured cells and
      bind purinergic-type 2 receptors (P2-Rs) that modulate inflammatory responses.
      Ectonucleotidases, such as CD39/nucleoside triphosphate diphosphohydrolase-1,
      hydrolyze extracellular nucleotides to integrate purinergic signaling responses.
      Because the role of extracellular nucleotides and CD39 in mediating inflammation
      and fibrosis are understood poorly, we studied the impact of CD39 gene deletion
      in a model of pancreatic disease. METHODS: Pancreatitis was induced by
      cyclosporine pretreatment, followed by cerulein injections (50 mug/kg, 6
      intraperitoneal injections/day, 3 times/wk); mice were killed at day 2, week 3,
      and week 6. Experimental parameters were correlated with cytokine levels in
      blood, RNA, and protein expression of purinergic and fibrosis markers in tissues.
      Immunohistochemistry and pancreatic morphometry of fibrosis were performed in
      wild-type and CD39-null mice. Effects of CD39 deletion on proliferation of
      primary pancreatic stellate cells (PSCs) were investigated in vitro. RESULTS:
      Wild-type mice developed morphologic features of pancreatitis with the
      anticipated development of parenchymal atrophy and fibrosis. CD39 and P2-R became
      overexpressed in vascular and adventitious wild-type tissues. In contrast, CD39
      null mice had inflammatory reactions but developed only minor pancreatic atrophy
      and limited fibrosis. Interferon-gamma became significantly increased in tissues
      and plasma of CD39-null mice. Wild-type PSCs expressed high levels of CD39 and P2
      R. CD39-null PSCs showed decreased rates of proliferation and the expression of
      procollagen-alpha1 was inhibited significantly in vitro (P < .03). CONCLUSIONS:
      CD39 deletion decreases fibrogenesis in experimental pancreatitis. Our data
      implicate extracellular nucleotides as modulators of PSC proliferation and
      collagen production in pancreatitis.

PMID- 18036595
TI  - Blocks and bodies: sex differences in a novel version of the Mental Rotations
      Test.
AB  - A novel version of the Mental Rotations Test (MRT) that alternated the standard
      block figures with three-dimensional human figures was administered to 99 men and
      129 women. Women and men differed predictably in their retrospective reports of
      childhood play and digit ratios, a putative measure of prenatal androgen action.
      Compared to the block figure items, human figure items on the modified MRT were
      associated with an improvement in performance in both sexes. However, consistent
      with the study hypothesis, the enhancing effect of the human figure condition on
      performance as measured by conventional scores was smaller in men compared to
      women and not at all evident in men when performance was measured by ratio
      scores. A closer inspection of the human figures effects on test scores showed
      performance in women improved for both male and female figure items. In contrast,
      relative to scores on block figure items, performance in men improved when
      stimuli were male figures but did not improve when stimuli were female figures.
      These results add to the evidence that the magnitude of sex differences in scores
      on the MRT may vary according to the test content and item properties. The
      findings suggest that online measures of cognitive processing in response to
      different classes of test stimuli (e.g., animate vs. inanimate objects, self
      relevant vs. neutral stimuli) may prove useful in research aimed at understanding
      the hormonal and social factors contributing to the sex difference in performance
      on the MRT.

PMID- 18036596
TI  - Combined effects of DHEA and fadrozole on aggression and neural VIP
      immunoreactivity in the non-breeding male song sparrow.
AB  - The male Song Sparrow, Melospiza melodia morphna, shows high levels of aggression
      in its non-breeding season, concomitant with basal levels of circulating
      testosterone (T) and estradiol (E(2)). However, administration of fadrozole, an
      aromatase inhibitor, decreases non-breeding aggression in the field. Circulating
      levels of dehydroepiandrosterone (DHEA), an androgen/estrogen precursor,
      correspond to the seasonal expression of aggression in this species, with high
      levels in the breeding and non-breeding seasons when aggression is also high, and
      lower levels during the molt when aggression is low. We test the hypothesis that
      circulating DHEA up-regulates non-breeding aggression via an aromatase-mediated
      mechanism. We also hypothesize that this up-regulation of aggression is partially
      mediated by changes in vasoactive intestinal polypeptide (VIP) in the lateral
      extent of the bed nucleus of the stria terminalis (BSTl) and lateral septum (LS).
      Birds were administered either DHEA, fadrozole, or both for 2 weeks and tested
      for aggression in a lab-based paradigm. As predicted, birds given DHEA were
      significantly more aggressive. However, fadrozole did not block this effect, and,
      when administered without DHEA, also led to increased aggression over controls.
      These results may be explained by the fact that the behaviors measured in field
      tests, which include more direct attack behaviors, may be under different
      hormonal regulation than the behaviors measured in the lab paradigm, which
      represent warning, or threat, behaviors. VIP immunoreactivity (VIP-ir) changed
      across multiple brain regions with this treatment regimen, most notably in the
      LSO/VFI subdivision of the lateral septum.

PMID- 18036597
TI  - Kinematics estimation of straddled movements on high bar from a limited number of
      skin markers using a chain model.
AB  - To reduce the effects of skin movement artefacts and apparent joint dislocations
      in the kinematics of whole body movement derived from marker locations, global
      optimisation procedures with a chain model have been developed. These procedures
      can also be used to reduce the number of markers when self-occlusions are hard to
      avoid. This paper assesses the kinematics precision of three marker sets: 16, 11
      and 7 markers, for movements on high bar with straddled piked posture. A three
      dimensional person-specific chain model was defined with 9 parameters and 12
      degrees of freedom and an iterative procedure optimised the gymnast posture for
      each frame of the three marker sets. The time histories of joint angles obtained
      from the reduced marker sets were compared with those from the 16 marker set by
      means of a root mean square difference measure. Occlusions of medial markers
      fixed on the lower limb occurred when the legs were together and the pelvis
      markers disappeared primarily during the piked posture. Despite these occlusions,
      reconstruction was possible with 16, 11 and 7 markers. The time histories of
      joint angles were similar; the main differences were for the thigh mediolateral
      rotation and the knee flexion because the knee was close to full extension. When
      five markers were removed, the average angles difference was about 3 degrees .
      This difference increased to 9 degrees for the seven marker set. It is concluded
      that kinematics of sports movement can be reconstructed using a chain model and a
      global optimisation procedure for a reduced number of markers.

PMID- 18036598
TI  - Contribution of solid-phase hexapeptide ligand libraries to the repertoire of
      human bile proteins.
AB  - Proteins in bile may have important physiological functions and serve as disease
      biomarkers. Here, the protein composition of human gallbladder bile was analyzed
      using a recently described chromatography-like technology capable to enhance the
      signal of low-abundance species. First, proteins present in bile fluid were
      treated with immobilized peptide ligand libraries to concentrate dilute and very
      dilute species while concomitantly diluting the high-abundance proteins. The
      analysis of resulting protein mixture was then performed using LC-MS/MS after
      having classically separated proteins by a mini preparative gel electrophoresis.
      Overall 222 gene products were found; 143 of them were not reported before in
      proteomics studies. Ligand libraries by themselves contributed to find 81 new
      gene products distributed throughout different categories. The described
      chromatographic approach provides a significant contribution to the bile protein
      repertoire and opens new perspectives for the discovery of markers for specific
      biliary tract diseases.

PMID- 18036599
TI  - Application of micellar electrokinetic capillary chromatography for evaluation of
      inhibitory effects on cytochrome P450 reaction.
AB  - The major aim of this work is to demonstrate the applicability of micellar
      electrokinetic capillary chromatography with SDS based pseudostationary phase for
      the screening of cytochrome P450 inhibitors. In contrast with the other capillary
      electrophoresis modes the cytochrome P450 reaction mixture thus could be used for
      the analysis without any pre-treatment. Cytochrome P450 2C9, one of the most
      important isoforms in human liver, was chosen as a model example for this study
      in combination with diclofenac as a probe substrate. The inhibitory effect on the
      given cytochrome P450 reaction was evaluated for two inhibitors with different
      inhibition potential - strong inhibitor sulfaphenazole and moderate inhibitor
      ketoconazole. As a result 50% inhibitory concentrations IC(50) and inhibition
      constants K(i) were evaluated; their values for both inhibitors were in a good
      agreement with the literature data determined by different methods.

PMID- 18036600
TI  - High peak capacity separations of peptides in reversed-phase gradient elution
      liquid chromatography on columns packed with porous shell particles.
AB  - The performance of 5 and 15 cm long columns packed with shell particles (Halo,
      AMT) is compared in gradient elution separations of the tryptic digests of
      myoglobin and bovine serum albumin. The influences of the temperature and the
      mobile phase flow rate on the column efficiency for two peptides are discussed.
      The influences of this flow rate, of the temperature, and of the gradient slopes
      on the peak capacities are also considered. Peak capacities in excess of 400 were
      achieved in 6h with the longer column. Peak capacities of 200 could be achieved
      in 30 min with the shorter column.

PMID- 18036601
TI  - Study of assembly of arachidic acid/LDHs hybrid films containing photoactive
      dyes.
AB  - Hybrid monolayers formed with an floating arachidic acid (AA) anions monolayer
      binding with a densely packed layered double hydroxides (LDHs) monolayer at an
      air/LDHs suspension interface has been studied by pi-A isotherms and TEM images.
      An ordered multilayer film of AA/LDHs has been fabricated by Langmuir-Blodgett
      technique on various substrates. The photoactive dyes (methyl orange, MO, and
      Congo red, CR) can be incorporated into the galleries of LDHs in the AA/LDHs
      hybrid LB film by an ion intercalation method. The results of FTIR and UV-vis
      absorption spectra can approve the formation of AA/LDHs/dyes composite films. In
      addition, UV-vis absorption spectra and LAXRD analyses also provide evidence for
      the good vertical uniformity and stable layered periodic structure of
      AA/LDHs/dyes films. More interestingly, it was found that the dye molecules
      intercalated can be induced by a positively charged LDHs sheet to align in a
      special orientation and form different aggregates: MO molecules form sandwich H
      type aggregates, while CR molecules form head-to-tail J-type aggregates. On the
      basis of these data, a possible model of the AA/LDHs/dyes composite films was
      proposed. Also, the dye molecules incorporated into AA/LDHs films exhibit
      excellent configuration stability under the irradiation of UV light because the
      LDHs matrix offers a more rigid and constrained environment for them.

PMID- 18036602
TI  - Effect of ionic surfactants on drainage and equilibrium thickness of emulsion
      films.
AB  - This paper presents new theoretical and experimental results that quantify the
      role of surfactant adsorption and the related interfacial tension changes and
      interfacial forces in the emulsion film drainage and equilibrium. The
      experimental results were obtained with plane-parallel microscopic films from
      aqueous sodium dodecyl sulphate solutions formed between two toluene droplets
      using an improved micro-interferometric technique. The comparison between the
      theory and the experimental data show that the emulsion film drainage and
      equilibrium are controlled by the DLVO interfacial forces. The effect of
      interfacial viscosity and interfacial tension gradient (the Marangoni number) on
      the film drainage is also significant.

PMID- 18036603
TI  - Flexible transparent conducting single-wall carbon nanotube film with network
      bridging method.
AB  - We fabricated random network films of highly pure single-wall carbon nanotubes
      (SWCNTs) on flexible polyethylene terephthalate substrate by dip- and spray
      coatings and their combination method for application to flexible transparent
      conducting films (TCFs). The dip-coating treatment was a more efficient method
      for fabricating the SWCNT-TCFs of high electrical conductivity without drastic
      drop in the optical transmittance, compared to the spray-coating one. This should
      be primarily due to more loose contact in intertube and interbundle junctions of
      the spray-coated SWCNT networks. Although the electrical conductivity of the
      SWCNT-TCFs was dramatically enhanced as increasing the number of dipping times,
      the dip-coating treatment with a large number of dipping times considerably
      reduced the transmittance without corresponding improvement in the electrical
      conductivity, indicating the patch-wise coating of the SWCNTs. On the other hand,
      the combination of the spray- and dip-coatings gave a supplementary effect for
      formation of a highly transparent film of better electrical conductivity. For
      SWCNT-TCF coated with 100 dipping times, an additional spray-coating dramatically
      decreased the sheet resistance from 1300 to 340 Omega/square, which is
      accompanied by slight reduction of the transmittance from 88 to 80%. Therefore,
      the post spray-coating can efficiently bridge the patch-wise SWCNT networks
      produced by the successive dip-coating.

PMID- 18036604
TI  - Voltammetric behavior of cefdinir in solubilized system.
AB  - The voltammetric behavior of cefdinir has been studied in different surfactant
      media viz. anionic, neutral, and cationic surfactants over the pH range 2.5-12 in
      phosphate buffer (0.2 M). Addition of cationic surfactant (citrimide) to the
      cefdinir containing electrolyte enhanced the reduction current signal while
      anionic surfactant (sodium lauryl) and neutral surfactant (Tween-20) showed an
      opposite effect. The reduction process was irreversible over the entire pH range
      studied (2.5-12). The mechanism of reduction has been postulated on the basis of
      controlled potential electrolysis, coulometry and spectral analysis. An
      analytical method with adequate precision and accuracy was developed for the
      determination of cefdinir in linear concentration range 2x10(-4)-1x10(-5) mol L(
      1) with detection limit 0.3x10(-6) mol L(-1). The analysis of cefdinir in its
      pharmaceutical formulation resulted in mean recoveries of 99 and 98% for both the
      reduction peaks.

PMID- 18036605
TI  - Adsorption of Pb2+, Zn2+, and Cd2+ from waters by amorphous titanium phosphate.
AB  - In the current study, amorphous titanium phosphate (TiP) was prepared as an
      adsorbent for heavy metals from waters. Uptake of Pb(2+), Zn(2+), and Cd(2+) onto
      TiP was assayed by batch tests; a polystyrene-sulfonic acid exchanger D-001 was
      selected for comparison and Ca(2+) was chosen as a competing cation due to its
      ubiquitous occurrence in waters. The pH-titration curve of TiP implied that
      uptake of heavy metals onto TiP is essentially an ion-exchange process. Compared
      to D-001, TiP exhibits more preferable adsorption toward Pb(2+) over Zn(2+) and
      Cd(2+) even in the presence of Ca(2+) at different levels. FT-IR analysis of the
      TiP samples laden with heavy metals indicated that the uptake of Zn(2+) and
      Cd(2+) ions onto TiP is mainly driven by electrostatic interaction, while that of
      Pb(2+) ions is possibly dependent upon inner-sphere complex formation, except for
      the electrostatic interaction. Moreover, uptake of heavy metals onto TiP
      approaches equilibrium quickly and the exhausted TiP particles could be readily
      regenerated by HCl solution.

PMID- 18036606
TI  - Comparison of hybridoma screening methods for the efficient detection of high
      affinity hapten-specific monoclonal antibodies.
AB  - This study compares diverse microplate-based hybridoma screening methods for the
      generation of hapten-(aflatoxin-) specific monoclonal antibodies (MAbs). Standard
      indirect enzyme-linked immunosorbent assay (ELISA) screenings (with
      immobilization of hapten-protein conjugate and use of enzyme-labeled anti-mouse
      IgG as tracer) were compared with direct ELISAs (with antibody immobilization and
      use of a hapten-enzyme conjugate as tracer). Although direct ELISA is rarely used
      for routine hybridoma screenings, it showed considerable advantages compared to
      the indirect assays. Standard indirect ELISA screening can lead to a considerable
      number of false positives (up to about 50% false positives of all 373
      supernatants tested) if the antibody concentrations in the supernatants are too
      high. Direct ELISAs gave useful screening results for the different supernatant
      dilutions chosen. At most 3 false positives were detected out of 373
      supernatants. However, the sensitivity of the direct ELISA screening is generally
      lower compared to indirect ELISA, and individual high-affinity MAbs might be
      classified as false negative. Therefore, a modified indirect ELISA screening was
      also developed. It includes pre-incubation of the supernatants in anti-mouse IgG
      coated microplates which are then transferred into the (indirect) hapten
      conjugate-coated microplates. This screening method leads to excellent results
      with good overall selectivity and sensitivity. It can also be conveniently
      combined with the direct ELISA screening. Using these improved screening methods,
      aflatoxin-specific MAbs could be generated with IC50 values down to 3 ng/l
      (aflatoxin concentration).

PMID- 18036608
TI  - Determining blood cell size using microfluidic hydrodynamics.
AB  - Microfluidic flow cytometers currently analyze far fewer parameters than
      conventional flow cytometry or fluorescence activated cell sorting (FACS) in
      order to minimize cost and complexity. There is a need for microfluidic devices
      that analyze more and or new cell parameters with compact and minimal means. Here
      we show a new and explicitly microfluidic parameter, "hydrodynamic" cell size,
      and compare it to forward scatter in conventional flow cytometry. The
      hydrodynamic size of cells is determined by the degree of lateral displacement
      experienced while traveling through a 1.2-mm-wide non-clogging array of micro
      fabricated obstacles. We show comparable size resolution between the microfluidic
      device and forward scatter in conventional flow cytometry and without the need to
      lyse red blood cells. We use the device to differentiate healthy lymphocytes from
      malignant lymphocytes by size alone and we use the device to detect increased
      numbers of activated lymphocytes in blood as a result of exposure to
      staphylococcal enterotoxin B (SEB), a potential bioterror agent. Together the
      results demonstrate a microfluidic device that performs some of the measurement
      and separation tasks of a flow cytometer but at a potentially lower cost and
      complexity.

PMID- 18036607
TI  - Quantitative imaging assay for NF-kappaB nuclear translocation in primary human
      macrophages.
AB  - Quantitative measurement of NF-kappaB nuclear translocation is an important
      research tool in cellular immunology. Established methodologies have a number of
      limitations, such as poor sensitivity, high cost or dependence on cell lines.
      Novel imaging methods to measure nuclear translocation of transcriptionally
      active components of NF-kappaB are being used but are also partly limited by the
      need for specialist imaging equipment or image analysis software. Herein we
      present a method for quantitative detection of NF-kappaB rel A nuclear
      translocation, using immunofluorescence microscopy and the public domain image
      analysis software ImageJ that can be easily adopted for cellular immunology
      research without the need for specialist image analysis expertise and at low
      cost. The method presented here is validated by demonstrating the time course and
      dose response of NF-kappaB nuclear translocation in primary human macrophages
      stimulated with LPS, and by comparison with a commercial NF-kappaB activation
      reporter cell line.

PMID- 18036609
TI  - Role for calcium in the development of ovarial patency in Heliothis virescens.
AB  - Insect oocytes sequester nutritive proteins from the hemolymph under the
      regulation by juvenile hormone (JH), in a process called patency. Here, a
      pharmacological approach was used to decipher the role for calcium in ovarial
      patency in the moth, Heliothis virescens. Follicular epithelial cells were
      exposed in calcium-free or calcium-containing media to JH I, JH II or JH III
      alone, or in combination with various inhibitors of signal transduction. Protein
      kinase inhibitors, Na(+)/K(+) -ATPase inhibitor, ouabain, an inhibitor of voltage
      dependent calcium channels in plasma membrane, omega-Conotoxin MVII, endoplasmic
      reticulum (ER) Ca(2+) -ATPase inhibitor, thapsigargin, ER inositol 1,4,5
      triphosphate receptor (IP(3)R) inhibitor, 2-ABP and ER ryanodine receptor (RyR)
      inhibitor, ryanodine, were used. The results of our study suggest that JH II
      evokes patency via protein kinase C-dependent signaling pathway, and activation
      of Na(+)/K(+) -ATPase, similar to JH III. Response to JH II and JH III
      predominantly relies upon external and internal calcium stores, using voltage
      dependent calcium channels, IP(3)Rs and RyRs. In contrast, regulation of patency
      by JH I appears to be largely calcium independent, and the calcium-dependent
      component of the signaling pathway likely does not use IP(3)Rs, but RyRs only.
      The JH II, JH III and calcium-dependent component of JH I signaling pathway
      probably utilize calcium/calmodulin-dependent kinase II for activation of
      Na(+)/K(+) -ATPase.

PMID- 18036610
TI  - Selective translation of mRNAs in the left ventricular myocardium of the mouse in
      response to acute pressure overload.
AB  - During pressure overload hypertrophy, selective changes in cardiac gene
      expression occur that regulate growth and modify the structural and functional
      properties of the myocardium. To determine the role of translational mechanisms,
      a murine model of transverse aortic constriction was used to screen a set of
      specified mRNAs for changes in translational activity by measuring incorporation
      into polysomes in response to acute pressure overload. Candidate mRNAs were
      selected on the basis of two main criteria: (1) the 5'-untranslated region of the
      mRNA contains an excessive amount of secondary structure (DeltaG<-50 kCal/mol),
      which is postulated to regulate efficiency of translation, and (2) the protein
      product has been implicated in the regulation of cardiac hypertrophy. After 24 h
      of transverse aortic constriction, homogenates derived from the left ventricle
      were layered onto 15-50% linear sucrose gradients and resolved into monosome
      fractions (messenger ribonucleoprotein particles) and polysome fractions by
      density gradient ultracentrifugation. The levels of mRNA in each fraction were
      quantified by real-time RT-PCR. The screen revealed that pressure overload
      increased translational activity of 6 candidate mRNAs as determined by a
      significant increase in the percentage of total mRNA incorporated into the
      polysome fractions. The mRNAs code for several functional classes of proteins
      linked to cardiac hypertrophy: the transcription factors c-myc, c-jun and MEF2D,
      growth factors VEGF and FGF-2 and the E3 ubiquitin ligase MDM2. These studies
      demonstrate that acute pressure overload alters cardiac gene expression by
      mechanisms that selectively regulate translational activity of specific mRNAs.

PMID- 18036611
TI  - Amyloid toxicity is independent of polypeptide sequence, length and chirality.
AB  - By using an amyloid sequence pattern, here we have identified putative six
      residue amyloidogenic stretches in several relevant amyloid proteins.
      Hexapeptides synthesized on the bases of the sequence stretches matching the
      pattern have been shown to form amyloid fibrils in vitro. As larger pathological
      peptides such as A beta(1-42) do, these short amyloid peptides form heterogeneous
      mixtures of small aggregates that induce cell death in PC12 cells and primary
      hippocampal neurons. Toxic mixtures of small aggregates from these hexapeptides
      bind to cell membranes and can be further internalized, as also observed for
      natural amyloid proteins. In neurons, toxic aggregates obtained from the full
      length A beta(1-42) amyloid peptide or their amyloid stretch A beta(16-21)
      peptide preferentially localize in synapses, leading to the re-organization of
      the underlying actin cytoskeleton. This process does not involve stereospecific
      interactions between membrane and toxic species as D-sequences are as toxic as L
      ones, suggesting that is not receptor mediated. Based on these results, we
      propose here that regardless of polypeptide sequence, length and amino acid
      chirality, amyloid prefibrillar aggregates exert their cytotoxic effect through a
      common cell death mechanism related to a particular quaternary structure. The
      degree of toxicity of these species seems to depend, however, on cell membrane
      composition.

PMID- 18036612
TI  - Molecular docking for substrate identification: the short-chain
      dehydrogenases/reductases.
AB  - Protein ligand docking has recently been investigated as a tool for protein
      function identification, with some success in identifying both known and unknown
      substrates of proteins. However, identifying a protein's substrate when cross
      docking a large number of enzymes and their cognate ligands remains a challenge.
      To explore a more limited yet practically important and timely problem in more
      detail, we have used docking for identifying the substrates of a single protein
      family with remarkable substrate diversity, the short-chain
      dehydrogenases/reductases. We examine different protocols for identifying
      candidate substrates for 27 short-chain dehydrogenase/reductase proteins of known
      catalytic function. We present the results of docking >900 metabolites from the
      human metabolome to each of these proteins together with their known cognate
      substrates and products, and we investigate the ability of docking to (a)
      reproduce a viable binding mode for the substrate and (b) to rank the substrate
      highly amongst the dataset of other metabolites. In addition, we examine whether
      our docking results provide information about the nature of the substrate, based
      on the best-scoring metabolites in the dataset. We compare two different docking
      methods and two alternative scoring functions for one of the docking methods, and
      we attempt to rationalise both successes and failures. Finally, we introduce a
      new protocol, whereby we dock only a set of representative structures (medoids)
      to each of the proteins, in the hope of characterising each binding site in terms
      of its ligand preferences, with a reduced computational cost. We compare the
      results from this protocol with our original docking experiments, and we find
      that although the rank of the representatives correlates well with the mean rank
      of the clusters to which they belong, a simple structure-based clustering is too
      naive for the purpose of substrate identification. Many clusters comprise ligands
      with widely varying affinities for the same protein; hence important candidates
      can be missed if a single representative is used.

PMID- 18036613
TI  - Malarial EBA-175 region VI crystallographic structure reveals a KIX-like binding
      interface.
AB  - The malaria parasite proliferates in the bloodstream of its vertebrate host by
      invading and replicating within erythrocytes. To achieve successful invasion, a
      number of discrete and essential events need to take place at the parasite-host
      cell interface. Erythrocyte-binding antigen 175 (EBA-175) is a member of a family
      of Plasmodium falciparum erythrocyte-binding proteins involved in the formation
      of a tight junction, a necessary step in invasion. Here we present the crystal
      structure of EBA-175 region VI (rVI), a cysteine-rich domain that is highly
      conserved within the protein family and is essential for EBA-175 trafficking. The
      structure was solved by selenomethionine single-wavelength anomalous dispersion
      at 1.8 A resolution. It reveals a homodimer, containing in each subunit a compact
      five-alpha-helix core that is stabilized by four conserved disulfide bridges. rVI
      adopts a novel fold that is likely conserved across the protein family,
      indicating a conserved function. It shows no similarity to the Duffy-binding-like
      domains of EBA-175 involved in erythrocyte binding, indicating a distinct role.
      Remarkably, rVI possesses structural features related to the KIX-binding domain
      of the coactivator CREB-binding protein, supporting the binding and trafficking
      roles that have been ascribed to it and providing a rational basis for further
      experimental investigation of its function.

PMID- 18036614
TI  - Human intestinal maltase-glucoamylase: crystal structure of the N-terminal
      catalytic subunit and basis of inhibition and substrate specificity.
AB  - Human maltase-glucoamylase (MGAM) is one of the two enzymes responsible for
      catalyzing the last glucose-releasing step in starch digestion. MGAM is anchored
      to the small-intestinal brush-border epithelial cells and contains two homologous
      glycosyl hydrolase family 31 catalytic subunits: an N-terminal subunit (NtMGAM)
      found near the membrane-bound end and a C-terminal luminal subunit (CtMGAM). In
      this study, we report the crystal structure of the human NtMGAM subunit in its
      apo form (to 2.0 A) and in complex with acarbose (to 1.9 A). Structural analysis
      of the NtMGAM-acarbose complex reveals that acarbose is bound to the NtMGAM
      active site primarily through side-chain interactions with its acarvosine unit,
      and almost no interactions are made with its glycone rings. These observations,
      along with results from kinetic studies, suggest that the NtMGAM active site
      contains two primary sugar subsites and that NtMGAM and CtMGAM differ in their
      substrate specificities despite their structural relationship. Additional
      sequence analysis of the CtMGAM subunit suggests several features that could
      explain the higher affinity of the CtMGAM subunit for longer maltose
      oligosaccharides. The results provide a structural basis for the complementary
      roles of these glycosyl hydrolase family 31 subunits in the bioprocessing of
      complex starch structures into glucose.

PMID- 18036616
TI  - The persistence of the placebo response in antidepressant clinical trials.
AB  - Our objective was to assess the persistence of the placebo response during at
      least 12 weeks of continued placebo administration in depressed patients who have
      responded to 6-8 weeks of acute placebo treatment. We identified 8 placebo
      controlled antidepressant trials with a total of 3,063 depressed patients in
      which, after acute phase placebo treatment, placebo was continued for more than
      12 weeks. The number of patients entering the continuation phase and percentages
      relapsing during this phase were determined. Based on the total number of
      patients entering the continuation phase 79% of placebo responders remained well
      (did not meet relapse criteria) during this phase compared to 93% of
      antidepressant responders. Although significantly more patients on placebo than
      on antidepressants relapsed in the continuation phase, 4 out of 5 placebo
      responders stayed well. The widely held belief that the placebo response in
      depression is short-lived appears to be based largely on intuition and perhaps
      wishful thinking.

PMID- 18036618
TI  - DO-increasing effects of a microscopic bubble generating system in a fish farm.
AB  - We have developed a "microscopic bubble generating system for the fish farm" and
      evaluated its ability to improve the quality of seawater and costs of it in
      marine cages of red sea bream (Pagrus major) in Kusuura Bay, Japan. Our results
      revealed that DO concentration of bubbling net pens increased and became
      significantly higher than the level outside the net pen (between 0.52 and 0.87
      mg/L), and the whole water column was nearly saturated. Temperatures of the
      bubbling net pens decreased slightly between 0.08 and 0.12 degrees C in all the
      layers. Furthermore, micro-bubbles seemed to reach the deeper water due to the
      downward flow and diffusion. This study demonstrated that the microscopic bubble
      generating system developed in our research project could increase efficiently
      the dissolved oxygen concentration throughout all water layers of the fish farm.
      A capital and operation costs of the system is recoverable within a year.

PMID- 18036615
TI  - The stator complex of the A1A0-ATP synthase--structural characterization of the E
      and H subunits.
AB  - Archaeal ATP synthase (A-ATPase) is the functional homolog to the ATP synthase
      found in bacteria, mitochondria and chloroplasts, but the enzyme is structurally
      more related to the proton-pumping vacuolar ATPase found in the endomembrane
      system of eukaryotes. We have cloned, overexpressed and characterized the stator
      forming subunits E and H of the A-ATPase from the thermoacidophilic Archaeon,
      Thermoplasma acidophilum. Size exclusion chromatography, CD, matrix-assisted
      laser desorption ionization time-of-flight mass spectrometry and NMR
      spectroscopic experiments indicate that both polypeptides have a tendency to form
      dimers and higher oligomers in solution. However, when expressed together or
      reconstituted, the two individual polypeptides interact with high affinity to
      form a stable heterodimer. Analyses by gel filtration chromatography and
      analytical ultracentrifugation show the heterodimer to have an elongated shape,
      and the preparation to be monodisperse. Thermal denaturation analyses by CD and
      differential scanning calorimetry revealed the more cooperative unfolding
      transitions of the heterodimer in comparison to those of the individual
      polypeptides. The data are consistent with the EH heterodimer forming the
      peripheral stalk(s) in the A-ATPase in a fashion analogous to that of the related
      vacuolar ATPase.

PMID- 18036617
TI  - Hydroxymethylglutaryl--CoA reductase inhibitor inhibits induction of nitric oxide
      synthase in 3T3--L1 preadipocytes.
AB  - Preadipocytes are considered to play a role in adipose tissue inflammation in
      obesity. The purpose of this study was to determine whether hydroxymethylglutaryl
      CoA reductase inhibitor (statin) modulates the nitric oxide (NO) production via
      inducible NO synthase (iNOS) in preadipocytes. Undifferentiated 3T3-L1 cells, a
      model of preadipocytes, significantly produced NO by the treatment with the
      combination of lipopolysaccharide (L), tumor necrosis factor-alpha (T) and
      interferon-gamma (I). Pre-incubation with simvastatin, a lipophilic statin, or
      pravastatin, a hydrophilic one, dose-dependently inhibited the NO production in
      the LTI-treated cells. The effect of simvastatin was offset by mevalonate or
      geranylgeranyl pyrophosphate (GGPP) but not by squalene. The mRNA level for iNOS
      paralleled the NO production. The nuclear factor-kappaB (NF-kappaB) was activated
      by the LTI-treatment, and was inhibited by addition of simvastatin or
      pravastatin. Mevalonate or GGPP completely offset the effect of simvastatin.
      Simvastatin or pravastatin also decreased the LTI-stimulated interleukin-6 (IL-6)
      secretion. These effects of pravastatin were relatively weak compared with those
      of simvastatin. Y27632, an inhibitor of Rho kinase, also inhibited the LTI
      induced NF-kappaB activation and iNOS expression, and decreased the production of
      NO and IL-6 in 3T3-L1 preadipocytes. These results suggest that statins,
      especially lipophilic types, inhibit induction of iNOS by inhibiting the small
      GTP-binding protein signal in preadipocytes.

PMID- 18036619
TI  - On board short-time high temperature heat treatment of ballast water: a field
      trial under operational conditions.
AB  - A ballast water short-time high temperature heat treatment technique was applied
      on board a car-carrier during a voyage from Egypt to Belgium. Ballast water from
      three tanks was subjected for a few seconds to temperatures ranging from 55
      degrees C to 80 degrees C. The water was heated using the vessel's heat exchanger
      steam and a second heat exchanger was used to pre-heat and cool down the water.
      The treatment was effective at causing mortality of bacteria, phytoplankton and
      zooplankton. The International Maritime Organization (IMO) standard was not
      agreed before this study was carried out, but comparing our results gives a broad
      indication that the IMO standard would have been met in some of the tests for the
      zooplankton, in all the tests for the phytoplankton; and probably on most
      occasions for the bacteria. Passing the water through the pump increased the kill
      rate but increasing the temperature above 55 degrees C did not improve the heat
      treatment's efficacy.

PMID- 18036620
TI  - Faecal-indicator bacteria and sedimentary processes in estuarine mudflats (Seine,
      France).
AB  - Over a three-year period, quantification of faecal indicators and the molecular
      detection of Escherichia coli and Salmonella were monitored in sediments from
      three contrasting mudflats of the Seine estuary (France). The elevation of the
      mudflat surface was monitored concurrently using a high-resolution altimeter.
      During the period of the study, estuarine mudflats were areas of deposition for
      faecal-indicator bacteria and were mainly controlled by sedimentary processes. In
      the intertidal freshwater and subtidal mudflats, the highest abundances of faecal
      indicator bacteria were counted during a depositional period. Maximum levels were
      observed in the freshwater mudflats during periods of high flow: thermotolerant
      coliforms: 3.9 x 10(4) cfu cm(-2), enterococci: 1.2 x 10(4) cfu cm(-2),
      Clostridium perfringens spores: 9.8 x 10(5) spores cm(-2). Loss of culturability
      of enteric bacteria in sediment microcosms demonstrated the remediatory capacity
      of the mudflats, even if they might be a secondary source of bacteria-forming
      spores to the water column through erosion and resuspension events.

PMID- 18036621
TI  - Assessment of methylmercury production in a temperate salt marsh (Ria de Aveiro
      Lagoon, Portugal).

PMID- 18036622
TI  - The succession of microbial community in the organic rich fish-farm sediment
      during bioremediation by introducing artificially mass-cultured colonies of a
      small polychaete, Capitella sp. I.
AB  - We monitored seasonal changes of the abundance and composition of microorganisms
      in the fish-farm sediment in Kusuura Bay, Amakusa, Japan, using the quinone
      profiling technique, during bioremediation by introducing cultured colonies of
      polychaete, Capitella sp. I. In November 2004, approximately 9.2 million cultured
      worms were transferred to the fish-farm sediment, which increased rapidly, and
      reached 458.5 gWW/m(2) (528,000 indiv./m(2)) in March 2005. During this fast
      increasing period of Capitella, the microbial quinone content of the surface
      sediment (0-2 cm) also increased markedly, and reached 237 micromol/m(2) in
      January 2005, although the water temperature decreased to the lowest levels in
      the year. Particularly, the mole fraction of ubiquinone-10 in total quinones in
      the sediment, indicating the presence of alpha subclass of Proteobacteria,
      increased by 9.3%. These facts suggest that the bacterial growth was enhanced
      markedly by the biological activities of worms in the sediment, and the bacteria
      played an important role in the decomposition of the organic matter in the
      sediment.

PMID- 18036623
TI  - Tracing sewage pollution in the Pearl River Delta and its adjacent coastal area
      of South China Sea using linear alkylbenzenes (LABs).

PMID- 18036624
TI  - An international comparison of governmental disclosure of hydrocarbon spills from
      offshore oil and gas installations.
AB  - The cumulative effect of accidental spills from oil and gas extraction in the
      marine environment can have significant impacts on marine wildlife. Oil and gas
      operators are typically required to report spill data as part of a regulatory
      process. We conducted a survey of the public disclosure of hydrocarbon spill data
      for four countries, Australia, Canada, United Kingdom and United States. There
      was significant variation in the spill data statistics that were publicly
      reported by the regulators. No country provided full disclosure of spill data or
      follow-up actions taken by the regulator on their website. The lack of disclosure
      of spill data is of concern because the scale of environmental effects is more
      difficult to assess, insufficient information is available to assess the accuracy
      of predictions made in the environmental assessment process, and without
      consistency of spill reporting there is no method to compare regional differences
      of spill rates.

PMID- 18036625
TI  - Postpubertal feeding experience affects sex-specific spatial ability in rats.
AB  - We previously reported that feeding with powdered diet after weaning (3 weeks of
      age) enhanced spatial ability, and increased the amount of acetylcholine (ACh)
      released in the dorsal hippocampus in female rats. In the present study, to
      specify the time when feeding conditions caused these effects, a radial 8-arm
      maze task and an in vivo microdialysis study were performed in both sexes of
      rats. In rats fed standard laboratory diet (i.e., pelleted diet), males learned
      the radial 8-arm maze faster than females. Moreover, the ACh release showed a
      distinct diurnal rhythm which was high during the dark phase and low during the
      light phase, but males showed a greater amount of ACh released in the dorsal
      hippocampus than females. However, in rats fed powdered diet after 6 weeks of
      age, no significant sex differences were observed in the radial 8-arm maze task
      or in the amount of ACh released, since feeding with powdered diet enhanced
      spatial ability, and increased the amount of ACh released only in females. These
      results suggest that feeding conditions after 6 weeks of age may contribute to
      the sex difference in the spatial ability associated with the changes in the
      amount of ACh released in the dorsal hippocampus in rats.

PMID- 18036626
TI  - Pathogen resistance of transgenic tobacco plants producing caffeine.
AB  - Caffeine (1,3,7-trimethylxanthine) is a typical purine alkaloid, and produced by
      a variety of plants such as coffee and tea. Its physiological function, however,
      is not completely understood, but chemical defense against pathogens and
      herbivores, and allelopathic effects against competing plant species have been
      proposed. Previously, we constructed transgenic tobacco plants, which produced
      caffeine up to 5 microg per gram fresh weight of leaves, and showed them to repel
      caterpillars of tobacco cutworms (Spodoptera litura). In the present study, we
      found that these transgenic plants constitutively expressed defense-related genes
      encoding pathogenesis-related (PR)-1a and proteinase inhibitor II under non
      stressed conditions. We also found that they were highly resistant against
      pathogens, tobacco mosaic virus and Pseudomonas syringae. Expression of PR-1a and
      PR-2 was higher in transgenic plants than in wild-type plants during infection.
      Exogenously applied caffeine to wild-type tobacco leaves exhibited the similar
      resistant activity. These results suggested that caffeine stimulated endogenous
      defense system of host plants through directly or indirectly activating gene
      expression. This assumption is essentially consistent with the idea of chemical
      defense, in which caffeine may act as one of signaling molecules to activate
      defense response. It is thus conceivable that the effect of caffeine is
      bifunctional; direct interference with pest metabolic pathways, and activation of
      host defense systems.

PMID- 18036627
TI  - First report of natural infection of a bush dog (Speothos venaticus) with
      Leishmania (Leishmania) chagasi in Brazil.
AB  - We report here the first known case of natural infection of a bush dog with
      Leishmania (Leishmania) chagasi in Brazil. The specimen was captured in the wild
      in the State of Mato Grosso and is currently being held in captivity at Fundacao
      Jardim Zoologico, Rio de Janeiro, Brazil. The leishmaniasis was diagnosed by
      culture of promastigote forms in intact skin fragments and their characterization
      by isoenzyme electrophoresis. This report calls attention to the parasitological
      and etiological control of certain zoonoses, such as leishmaniasis, in wild
      animals kept in captivity, especially when animals are exchanged between zoos in
      Brazil.

PMID- 18036628
TI  - Diethylstilbestrol inhibits phospholipase D activity and degranulation by
      stimulated human neutrophils.
AB  - In the present study the effects of diethylstilbestrol on phospholipase D
      activity and degranulation by human neutrophils were examined. Diethylstilbestrol
      is a synthetic estrogen and has structural similarity to resveratrol. Resveratrol
      is a natural polyphenolic antioxidant and has been shown to inhibit the activity
      of phospholipase D in stimulated neutrophils. Phospholipase D catalyzes the
      hydrolysis of phosphatidylcholine to yield phosphatidic acid and choline. It also
      catalyzes the transfer of the phosphatidyl group to ethanol forming
      phosphatidylethanol at the expense of phosphatidic acid. Phospholipase D
      activation is associated with degranulation by neutrophils stimulated with
      chemotactic peptide, formyl-methionyl-leucyl-phenylalanine. The results show that
      diethylstilbestrol at 100 microM induced a complete inhibition of phosphatidic
      acid formation in neutrophils, the latter activated by chemotactic peptide. In
      the presence of ethanol, diethylstilbestrol dose dependently reduced
      phosphatidylethanol formation induced by chemotactic peptide or by phorbol 12
      myristate 13-acetate, indicative of diethylstilbestyrol inhibition of
      phospholipase D activity. The results also demonstrate that diethylstilbestrol
      inhibited degranulation by chemotactic peptide-stimulated neutrophils. In
      comparison to resveratrol, diethylstilbestrol exhibits a stronger inhibition on
      PA formation, phospholipase D activity and degranulation. These findings suggest
      that diethylstilbestrol-like resveratrol, may have anti-inflammatory effect in
      vitro.

PMID- 18036629
TI  - Tissue dosimetry, metabolism and excretion of pentavalent and trivalent
      dimethylated arsenic in mice after oral administration.
AB  - Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary
      metabolite of administered inorganic arsenic in most mammals. This study examined
      the disposition of pentavalent and trivalent dimethylated arsenic in mice after
      acute oral administration. Adult female mice were administered [(14)C]-DMA(V)
      (0.6 or 60 mg As/kg) and sacrificed serially over 24 h. Tissues and excreta were
      collected for analysis of radioactivity. Other mice were administered unlabeled
      DMA(V) (0.6 or 60 mg As/kg) or dimethylarsinous acid (DMA(III)) (0.6 mg As/kg)
      and sacrificed at 2 or 24 h. Tissues (2 h) and urine (24 h) were collected and
      analyzed for arsenicals. Absorption, distribution and excretion of [(14)C]-DMA(V)
      were rapid, as radioactivity was detected in tissues and urine at 0.25 h. For low
      dose DMA(V) mice, there was a greater fractional absorption of DMA(V) and
      significantly greater tissue concentrations of radioactivity at several time
      points. Radioactivity distributed greatest to the liver (1-2% of dose) and
      declined to less than 0.05% in all tissues examined at 24 h. Urinary excretion of
      radioactivity was significantly greater in the 0.6 mg As/kg DMA(V) group.
      Conversely, fecal excretion of radioactivity was significantly greater in the
      high dose group. Urinary metabolites of DMA(V) included DMA(III), trimethylarsine
      oxide (TMAO), dimethylthioarsinic acid and trimethylarsine sulfide. Urinary
      metabolites of DMA(III) included TMAO, dimethylthioarsinic acid and
      trimethylarsine sulfide. DMA(V) was also excreted by DMA(III)-treated mice,
      showing its sensitivity to oxidation. TMAO was detected in tissues of the high
      dose DMA(V) group. The low acute toxicity of DMA(V) in the mouse appears to be
      due in part to its minimal retention and rapid elimination.

PMID- 18036630
TI  - Adenovirus E1A proteins are closely associated with chromatin in productively
      infected and transformed cells.
AB  - The adenovirus E1A 243R oncoprotein encodes a potent transcription-repression
      function within the N-terminal 80 amino acids. Our proposed model of E1A
      repression predicts that E1A interacts with important cellular proteins on
      chromatin. Consistent with this idea, we report here that E1A proteins from in
      vivo formaldehyde cross-linked 293 cells are closely associated with chromatin
      even after several stringent purification steps including double isopycnic CsCl
      density gradient centrifugation and size exclusion chromatography. Likewise, E1A
      proteins expressed from virus during productive infection of HeLa cells are
      closely associated with chromatin starting at early times after infection. No
      other adenoviral proteins are necessary for E1A 243R protein to associate with
      chromatin. Analyses of chromatin from HeLa cells infected with adenovirus vectors
      expressing E1A 243R protein with deletions in different E1A functional domains
      indicate that sequences within the E1A N-terminal repression domain are needed
      for the majority of E1A's interactions with chromatin.

PMID- 18036632
TI  - Formation of brominated products in irradiated titanium dioxide suspensions
      containing bromide and dissolved organic carbon.
AB  - We report the irradiation of TiO(2) suspensions containing Br(-) and dissolved
      organic carbon (DOC). In the absence of DOC, we found no evidence for the
      formation of BrO(3)(-) upon irradiation of 1gL(-1) P25 suspensions with UV light
      for initial Br(-) concentrations up to 10mgL(-1). In the presence of DOC (Lake
      Hohloh, Germany and salicylic acid), we found no evidence for the formation of
      either BrO(3)(-) or trihalomethanes (THMs). However, small amounts of adsorbable
      organic halogen (AOX) were formed at high bromide concentrations (3mgL(-1)). When
      irradiating P25 suspensions containing bromide and 2,4-dihydroxybenzoic acid
      (DHBA, high bromoform formation potential), we observed the formation of
      significant amounts of bromoform (up to 10microgL(-1)). Bromoform appeared only
      after the DHBA had been degraded.

PMID- 18036631
TI  - Analysis of centrosome overduplication in correlation to cell division errors in
      high-risk human papillomavirus (HPV)-associated anal neoplasms.
AB  - High-risk HPV-associated anal neoplasms are difficult to treat and biomarkers of
      malignant progression are needed. A hallmark of carcinogenic progression is
      genomic instability, which is frequently associated with cell division errors and
      aneuploidy. The HPV-16 E7 oncoprotein has been previously shown to rapidly induce
      centriole and centrosome overduplication and to cooperate with HPV-16 E6 in the
      induction of abnormal multipolar mitoses. Based on this function, it has been
      suggested that HPV-16 E7 may act as a driving force for chromosomal instability.
      However, a detailed analysis of centrosome overduplication in primary HPV
      associated neoplasms has not been performed so far. Here, we determined the
      frequency of centrosome overduplication in HPV-associated anal lesions using a
      recently identified marker for mature maternal centrioles, Cep170. We detected
      centrosome overduplication in a small but significant fraction of cells.
      Remarkably, centrosome overduplication, but not aberrant centrosome numbers per
      se or centrosome accumulation, correlated significantly with the presence of cell
      division errors. In addition, our experiments revealed that in particular pseudo
      bipolar mitoses may play a role in the propagation of chromosomal instability in
      high-risk HPV-associated tumors. These results provide new insights into the role
      of centrosome aberrations in cell division errors and encourage further studies
      on centrosome overduplication as a predictive biomarker of malignant progression
      in HPV-associated anal lesions.

PMID- 18036633
TI  - Age-related increase of tumor susceptibility is associated with myeloid-derived
      suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred
      BXD12 mice.
AB  - In this study, our data show that in young BXD12 mice, the implanted TS/A tumor
      regressed in 4 weeks after implantation, and this regression was associated with
      extensive T cell infiltration. In contrast, in old BXD12 mice, it was observed
      that there was rapid tumor growth by 7 weeks. T cell cytotoxicity against TS/A
      tumor cells exhibited a significant age-related decline, which was correlated
      with a decline in CD3(+) T cell infiltration of the tumor. Furthermore, the
      decline of T cell tumor cytotoxicity in aged BXD12 mice was also correlated with
      the accumulation of CD11b(+)Gr1(+) myeloid-derived suppressor cells in the
      spleen. Adoptive transfer of these accumulated CD11b(+)Gr1(+)cells from aged mice
      to 2-month-old BXD12 mice led to the delay of the rejection of implanted tumor
      cells. The depletion of CD11b(+)Gr1(+)cells from aged BXD12 mice led to the
      slower growth of tumor. Induction of arginase 1 in myeloid cells isolated from
      aged mice plays a partial role in immune suppression of T cell cytotoxicity.
      Thus, the accumulation of immunosuppresssing myeloid cells appears to contribute
      to the increase of tumor susceptibility as the age of mice increases.

PMID- 18036634
TI  - Chemical contaminants, health indicators, and reproductive biomarker responses in
      fish from rivers in the Southeastern United States.
AB  - Largemouth bass (Micropterus salmoides) and common carp (Cyprinus carpio) were
      collected from 13 sites located in the Mobile (MRB), Apalachicola-Flint
      Chattahoochee (ARB), Savannah (SRB), and Pee Dee (PRB) River Basins to document
      spatial trends in accumulative chemical contaminants, health indicators, and
      reproductive biomarkers. Organochlorine residues, 2,3,7,8-tetrachlorodibenzo-p
      dioxin-like activity (TCDD-EQ), and elemental contaminants were measured in
      composite samples of whole fish, grouped by species and gender, from each site.
      Mercury (Hg) and polychlorinated biphenyls (PCBs) were the primary contaminants
      of concern. Concentrations of Hg in bass samples from all basins exceeded
      toxicity thresholds for piscivorous mammals (>0.1 microg/g ww), juvenile and
      adult fish (>0.2 microg/g ww), and piscivorous birds (>0.3 microg/g ww). Total
      PCB concentrations in samples from the MRB, ARB, and PRB were >480 ng/g ww and
      may be a risk to piscivorous wildlife. Selenium concentrations also exceeded
      toxicity thresholds (>0.75 microg/g ww) in MRB and ARB fish. Concentrations of
      other formerly used (total chlordanes, dieldrin, endrin, aldrin, mirex, and
      hexachlorobenzene) and currently used (pentachlorobenzene, pentachloroanisole,
      dacthal, endosulfan, gamma-hexachlorocyclohexane, and methoxychlor)
      organochlorine residues were generally low or did not exceed toxicity thresholds
      for fish and piscivorous wildlife. TCDD-EQs exceeded wildlife dietary guidelines
      (>5 pg/g ww) in MRB and PRB fish. Hepatic ethoxyresorufin O-deethylase (EROD)
      activity was generally greatest in MRB bass and carp. Altered fish health
      indicators and reproductive biomarker were noted in individual fish, but mean
      responses were similar among basins. The field necropsy and histopathological
      examination determined that MRB fish were generally in poorer health than those
      from the other basins, primarily due to parasitic infestations. Tumors were found
      in few fish (n=5; 0.01%); ovarian tumors of smooth muscle origin were found in
      two ARB carp from the same site. Intersex gonads were identified in 47 male bass
      (42%) representing 12 sites and may indicate exposure to potential endocrine
      disrupting compounds. Comparatively high vitellogenin concentrations (>0.35
      mg/mL) in male fish from the MRB, SRB, and PRB indicate exposure to estrogenic or
      anti-androgenic chemicals.

PMID- 18036635
TI  - Selection and breeding of plant cultivars to minimize cadmium accumulation.
AB  - Natural variation occurs in the uptake and distribution of essential and
      nonessential trace elements among crop species and among cultivars within
      species. Such variation can be responsible for trace element deficiencies and
      toxicities, which in turn can affect the quality of food. Plant breeding can be
      an important tool to both increase the concentration of desirable trace elements
      and reduce that of potentially harmful trace elements such as cadmium (Cd).
      Selection programs for a low-Cd content of various crops, including durum wheat,
      sunflower, rice and soybean have been established and low-Cd durum wheat
      cultivars and sunflower hybrids have been developed. In durum wheat (Triticum
      turgidum L. var durum), low-Cd concentration is controlled by a single dominant
      gene. The trait is highly heritable, and incorporation of the low-Cd allele can
      help to reduce the average grain Cd to levels below proposed international
      limits. The allele for low-Cd concentration does not appear to affect major
      economic traits and should not cause problems when incorporated into durum
      cultivars. The cost of Cd selection in a breeding program is initially large both
      in terms of Cd determination and reduced progress towards development of other
      economic traits, but declines as more breeding lines in the program carry the low
      Cd trait and are utilized in new crosses. Production of low-Cd crop cultivars can
      be used as a tool to reduce the risk of movement of Cd into the human diet.

PMID- 18036636
TI  - Observations of long-lived anthropogenic halocarbons at the high-Alpine site of
      Jungfraujoch (Switzerland) for assessment of trends and European sources.
AB  - Anthropogenic halocarbons, such as chlorofluorocarbons (CFCs),
      hydrochlorofluorocarbons (HCFCs), hydrofluorocarbons (HFCs), bromocarbons
      (halons) and long-lived chlorinated solvents have been measured continuously at
      the high-Alpine site of Jungfraujoch (Switzerland) since January 2000. Chloro-
      and bromo-containing halocarbons are responsible for the stratospheric ozone
      depletion and will be globally banned from usage within the next years. With the
      exception of the stable CFC-12 (CF2 Cl2), all major CFCs and chlorinated solvents
      show a negative trend in recent years in their background concentrations at
      Jungfraujoch. HCFCs, as their first-generation substitute, are still increasing
      with a few percent per year. However, the frequency and the strength of HCFCs
      pollution events, which are caused by regional European emissions, are already
      declining. This can be seen as a sign of the impending ban of these gases within
      the next years in Europe. On the other hand, HFCs as the second-generation
      substitutes, are increasing with relative rates of at least 10% per year (e.g.
      almost 5 ppt per year for HFC-134a). An allocation of European sources was
      attempted by combining measured concentrations with trajectories of air masses
      reaching the Jungfraujoch during pollution events. Potential source regions could
      be detected in Italy, France, Spain and Germany.

PMID- 18036637
TI  - Evidence for preferential depths of metal retention in roots of salt marsh
      plants.
AB  - Depth variation (2-cm resolution) of Fe, Mn, Zn, Cr, Ni, Cu, As and Cd
      concentrations were determined in belowground biomass of Spartina maritima and
      Sarcocornia fruticosa and in sediments between roots from two marshes in Tagus
      (Rosario) and Guadiana (Castro Marim) estuaries in Portugal with different
      anthropogenic pressures. Levels of metals were also determined in aboveground
      plant parts. Metal concentrations in belowground material were 2-4 orders of
      magnitude greater than levels in aboveground plant parts providing evidence of
      weak upward translocation. Although both studied species showed poor extraction
      of Cr and Ni from sediments, S. fruticosa exhibited a large capability to remove
      Zn, Cu, As and Cd from contaminated sediments and stabilised them in belowground
      biomass. Accumulated metals showed a sub-surface concentration maximum or
      increase to basal roots. To evaluate whether these preferential layers of
      accumulation resulted from availability in sediments or controlled by plant
      activity, Enrichment Factors (EF=[Me](root)/[Metal](sediment)) were calculated
      for each sediment layer. Maximum values in Rosario plant species (Zn=9.3, Cu=18,
      As=20, Cd=46) exceeded those obtained in Castro Marim (Zn=1.3, Cu=4.3, As=6.1,
      Cd=18). Moreover, EFs varied with the depth indicating the presence of
      preferential layers of metal accumulation in roots of both plants, but depth
      zonation was not the same as in the sediments. These results suggested that
      levels in belowground biomass either integrated in time changes that occurred in
      solid sediments and pore water, or metal uptake by roots was not proportional to
      levels in sediments. The same sequence of metals transferred from sediment to
      belowground biomass for the two plants was obtained for the two marshes (Cd > As
      > Cu, Zn), although metals differed from mining ore to industrial/urban sources.

PMID- 18036638
TI  - Sub-cellular partitioning of Zn, Cu, Cd and Pb in the digestive gland of native
      Octopus vulgaris exposed to different metal concentrations (Portugal).
AB  - Concentrations of Zn, Cu, Cd and Pb and their sub-cellular distributions were
      determined in composite samples of digestive glands of the common octopus,
      Octopus vulgaris caught from two areas of the Portuguese coast characterised by
      contrasting metal contamination. Minor contents of Zn (1%), Cu (2%), Cd (6%) and
      Pb (7%) were found in the insoluble fraction, consisting of nuclei, mitochondria,
      lysosomes and microsome operationally separated from the whole digestive gland
      through a sequential centrifugation. A tendency for linear relationships between
      metal concentrations in nuclei, mitochondria, lysosomes and whole digestive gland
      was observed. These relationships suggest that despite low metal content
      organelles responded to the increasing accumulated metals, which means that
      detoxifying mechanism in cytosol was incomplete. Poorer correlations between
      microsome and whole digestive gland did not point to metal toxicity in the
      analysed compartments. However, the high accumulated Cd indicated that O.
      vulgaris is an important vehicle of this element to its predators in the coastal
      environment.

PMID- 18036639
TI  - Indoor air pollution in a Mexican indigenous community: evaluation of risk
      reduction program using biomarkers of exposure and effect.
AB  - Indoor air pollution can be an important risk factor for human health,
      considering that people spend more than 60% of their time indoors. Fifty percent
      of the world population and approximately 90% of the rural population in
      developing countries are using biomass as energy source. Latin America represents
      12% of the global consumption of biomass; in Mexico, 27 million people use wood
      as an energy source. Therefore, in this study we evaluated a 3-stage risk
      reduction program. The stages were: 1) removal of indoor soot adhered to roofs
      and internal walls; 2) paving the dirt floors; and 3) introduction of a new wood
      stove with a metal chimney that expels smoke outdoors. The complete intervention
      program was applied. In 20 healthy subject residents from an indigenous community
      in San Luis Potosi, Mexico, we measured blood carboxyhemoglobin (% COHb), DNA
      damage (comet assay) in nucleated blood cells, and urinary 1-OHP levels before
      and after the program. Before intervention individuals had a geometric mean COHb
      level of 4.93% and 53% of the population presented levels above 2.5% considered a
      safe level. However, in all the studied individuals the levels of COHb were
      reduced to below 2.5% (mean level 1.0%) one month after the intervention.
      Moreover, when compared, DNA damage in people exposed before the intervention was
      higher (5.8+/-1.3 of Tail Moment) than when the program was introduced (2.8+/-0.9
      of Tail Moment) (P>0.05) and a same trend was observed with urinary 1-OHP levels;
      6.71+/-3.58 micromol/mol creatinine was the concentration before intervention;
      whereas, 4.80+/-3.29 micromol/mol creatinine was the one after the program. The
      results suggest that the intervention program offers an acceptable risk reduction
      to those families that use biomass for food cooking.

PMID- 18036640
TI  - Correlation of NK T-like CD3+CD56+ cells and CD4+CD25+(hi) regulatory T cells
      with VEGF and TNFalpha in ascites from advanced ovarian cancer: Association with
      platinum resistance and prognosis in patients receiving first-line, platinum
      based chemotherapy.
AB  - BACKGROUND: Several cytokines have been associated with immune regulation and
      prognosis in ovarian cancer. CD4+CD25+ Tregs and CD3+CD56+ NK-like T cells are
      involved in the immune response against the tumor. We have investigated the
      association of cytokines in the ascites from patients with ovarian cancer with
      these populations, the platinum resistance and the prognosis of these patients.
      PATIENTS AND METHODS: Ascites from 64 patients with ovarian cancer was analysed.
      Forty-two patients were studied at diagnosis (FIGO stage III in 40 cases) and
      were treated with cytoreductive surgery and platinum-based chemotherapy. Ascites
      from 9 patients with cirrhosis was used as control. Vascular endothelial growth
      factor (VEGF), tumor necrosis factor-alpha (TNFalpha), interferon-gamma
      (IFNgamma), interleukin-10 (IL10) and interleukin-12 (IL12) in ascites and serum
      were measured by enzyme-linked immunosorbent assay (ELISA), while lymphocytic
      populations were studied with three-colour flow cytometry. RESULTS: VEGF ascites
      levels were inversely correlated with CD3+CD56+ cells (rho=-0.316, p=0.012),
      while a similar correlation was observed between TNFalpha ascites levels and
      CD4+CD25+(hi) cells (rho=-0.332, p=0.041). Among patients receiving first-line
      chemotherapy, VEGF levels <1900 pg/ml and TNFalpha levels >35 pg/ml were
      associated with platinum sensitivity (p=0.021 and p=0.028, respectively) and
      improved progression-free survival (PFS) (p=0.007 and p=0.045, respectively). Low
      VEGF levels were also associated with improved overall survival (p=0.026).
      CONCLUSION: VEGF and TNFalpha ascites levels are associated with prognosis in
      advanced ovarian cancer. Their prognostic significance may be due to their
      association with immunologically important populations, namely the NK T-like
      CD3+CD56+ cells and the Tregs CD4+CD25+(hi) cells.

PMID- 18036641
TI  - Epithelial-stromal interaction increases cell proliferation, survival and
      tumorigenicity in a mouse model of human epithelial ovarian cancer.
AB  - OBJECTIVE: Ovarian cancer is the fourth leading cause of cancer-related deaths
      among women and is among the least understood of all cancers. The objective of
      this study was to determine the effect of ovarian epithelial and stromal cell
      interaction in a mouse model of epithelial ovarian cancer (EOC) that closely
      resembled the human disease. METHODS: A mouse model of EOC was generated by
      orthotopic injection of an ID8 mouse ovarian surface epithelial cell line (MOSEC)
      under the ovarian bursa of syngeneic mice and tissue was collected to evaluate
      factors contributing to the formation and development of ovarian tumors. RESULTS:
      By 90 days post-injection, mice were moribund and had developed large primary
      ovarian tumors, secondary tumors within the peritoneal cavity, and extensive
      ascites fluid production. Tumors were hypervascularized and were characterized as
      serous epithelial carcinomatosis, which replicates the most common form of human
      ovarian cancer. Cells isolated from ascites fluid were more proliferative with
      increased expression of survival factors compared to original MOSEC cells and
      cells obtained from the abdomen following intraperitoneal injection. Orthotopic
      injection of these cells under the ovarian bursa resulted in more aggressive
      tumorigenesis, with mice becoming moribund at 60 days post-injection compared
      with 90 days post-injection with the original ID8-MOSEC cell line. DISCUSSION:
      This study describes the generation of an orthotopic, syngeneic model of ovarian
      cancer, which replicates the phenotype of the human disease. Expression of
      angiogenic and proliferative factors, and the interaction of epithelial cells
      with the ovarian stroma are important factors in ovarian tumorigenesis.

PMID- 18036642
TI  - Determinants of exhaled nitric oxide levels in healthy, nonsmoking African
      American adults.
AB  - BACKGROUND: Asthma is a significant cause of morbidity and mortality for African
      Americans. Fraction of exhaled nitric oxide (FeNO) levels are increased in
      patients with asthma, and airway levels of nitric oxide metabolites regulate
      airway inflammation and airway diameter. More needs to be known about the factors
      that regulate FeNO. There is a need for FeNO reference values for African
      Americans. OBJECTIVE: We sought to establish reference values and identify
      factors associated with FeNO levels in healthy African American adults. METHODS:
      FeNO levels were measured in 895 healthy, nonsmoking African Americans between
      the ages of 18 and 40 years. FeNO measurements were repeated in 84 subjects.
      Factors potentially associated with FeNO were measured, including blood pressure,
      height, weight, and serum total IgE, eosinophil cationic protein, C-reactive
      protein, and nitrate levels. Data on respiratory symptoms, including upper
      respiratory tract infection (URI) symptoms, were collected. Univariate and
      multivariate analyses of the relationship between these variables and FeNO levels
      were performed. RESULTS: In healthy, nonsmoking African Americans FeNO levels
      were stable during repeated measurements (intraclass correlation coefficient,
      0.81). Sex (P < .0001), serum total IgE levels (P < .0001), and current URI
      symptoms (P = .0002) contributed significantly to FeNO variability but together
      accounted for less than 50% of the variation in FeNO levels. CONCLUSION: The high
      correlation between repeated measurements of FeNO and the low correlation
      coefficients of known factors associated with FeNO suggest that other factors
      might contribute substantially to variability of FeNO levels in African
      Americans.

PMID- 18036643
TI  - Analytical bias of cross-reactive polyclonal antibodies for environmental
      immunoassays of Alternaria alternata.
AB  - BACKGROUND: Alternaria alternata is recognized as an important aeroallergen
      indoors and outdoors, and exposure to the fungus has been identified as a risk
      factor for asthma. Two recent publications concluded that 95% to 99% of American
      homes contained detectable amounts of Alternaria antigens when analyzed with a
      polyclonal antibody (pAb)-based ELISA. OBJECTIVES: We investigated the cross
      reactivity of the commercially available pAbs that were used in those studies.
      METHODS: Reactivity to 24 fungal species commonly found in indoor environments
      was analyzed by inhibition ELISA by using solid-phase A alternata antigen. The
      pAbs were also tested by immunoblotting and halogen immunoassay for a subgroup of
      fungi. RESULTS: Spores of 7 fungi including species of Alternaria, Ulocladium,
      Stemphylium, Epicoccum, Drechslera, and Exserohilum strongly inhibited the
      binding of the pAbs when tested by ELISA. Six other fungi reacted in the ELISA at
      a lower level, and 11 fungal species including several Penicillium, Aspergillus,
      Fusarium, and Cladosporium species failed to show inhibition. The immunoblots and
      the halogen immunoassay staining confirmed the cross-reactivity patterns of the
      ELISA. CONCLUSION: The pAbs against A alternata were found to cross-react broadly
      with related and nonrelated fungi. The prevalence data previously reported for A
      alternata should be considered to be fungal-reactive rather than A alternata
      specific.

PMID- 18036644
TI  - TGFB1 promoter polymorphism C-509T and pathophysiology of asthma.
AB  - BACKGROUND: TGF-beta1 can modulate airway inflammation and exaggerate airway
      remodeling. A polymorphism of a promoter region of TGFB1, C-509T, might be
      associated with the development of asthma, but its pathophysiologic relevance
      remains poorly understood. OBJECTIVE: We investigated relations of the C-509T
      polymorphism to airflow obstruction, sputum eosinophilia, and airway wall
      thickening, as assessed by means of computed tomography, in 85 patients with
      stable asthma. METHODS: The CC, CT, and TT genotypes were examined by means of
      PCR and restriction enzyme fragment length polymorphism. At a selected bronchus,
      3 indices of airway wall thickness were measured with an automatic method.
      RESULTS: The CC, CT, and TT genotypes were found in 22, 46, and 17 patients,
      respectively. Serum TGF-beta1 levels were significantly associated with the
      polymorphism and were increased in the CT/TT genotypes. FEV(1) and sputum
      eosinophil percentages were also significantly associated with the polymorphism
      and were both decreased in the CT/TT genotypes. The polymorphism was unrelated to
      airway wall thickness. CONCLUSION: In addition to increased serum TGF-beta1
      levels, the T allele of the C-509T polymorphism is related to increased airflow
      obstruction but attenuated eosinophilic inflammation. The former relation is not
      attributed to thickening of the central airway walls. The latter relation might
      reflect the anti-inflammatory effect of TGF-beta1. The C-509T polymorphism has a
      complex role in asthma pathophysiology, presumably because of the diverse
      functions of TGF-beta1 and its various interactions with cells and humoral
      factors in vivo.

PMID- 18036645
TI  - Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by
      using inhaled corticosteroids.
AB  - BACKGROUND: Indoleamine-2, 3-dioxygenase (IDO), a tryptophan-degrading enzyme,
      plays a key role in the regulation of T-lymphocyte function. IDO inhibits
      eosinophilic inflammation in a murine asthma model, but little is known about its
      role in asthmatic patients or the effects of corticosteroids on this key
      regulatory enzyme. OBJECTIVE: We studied IDO activity and the effect of inhaled
      corticosteroids (ICSs) in patients with asthma and how this correlated with
      eosinophilic inflammation. METHODS: After a 1-week run-in period on no therapy,
      34 asthmatic patients were treated with only short-acting beta(2)-agonists as
      required or an ICS or an ICS in combination with a long-acting beta(2)-agonist,
      which were required for asthma control, and the treatment was continued for a
      further 4 weeks. Each patient underwent sputum induction at the end of the run-in
      and treatment periods. Sputum supernatant specimens were analyzed for IDO
      activity and kynurenine concentrations by using HPLC. RESULTS: All patients with
      mild intermittent and mild-to-moderate persistent asthma had low baseline IDO
      activity in induced sputum compared with that seen in age-matched nonasthmatic
      subjects. The IDO activity was markedly enhanced by either ICS (P = .03) or
      ICS/long-acting beta(2)-agonist (P < .0001) treatment, and this increase
      negatively correlated with sputum eosinophils but was positively associated with
      an increase in IL-10-positive macrophages. CONCLUSION: ICSs might exert their
      anti-inflammatory activity in asthmatic airways, at least in part, through the
      upregulation of IDO activity associated with increased IL-10 secretion from
      macrophages.

PMID- 18036646
TI  - Identification of wheat gliadins as an allergen family related to baker's asthma.
AB  - BACKGROUND: Flour is still one of the most common causes of occupational asthma
      worldwide. Thus far, little is known about the relevant allergens causing baker's
      asthma. Therefore the reliability of current diagnostic procedures is
      insufficient. Only few of the suspected causative wheat allergens have been
      hitherto characterized on the molecular level. OBJECTIVE: The aim was to identify
      and characterize unknown wheat allergens related to baker's asthma to improve the
      reliability of diagnostic procedures. METHODS: A wheat pJuFo cDNA phage display
      library was created and screened for IgE binding to wheat proteins with pooled
      sera from patients with baker's asthma. After identifying an alphabeta-gliadin,
      the frequency of sensitization was investigated by means of ELISA screening of
      153 bakers' sera with the recombinant alphabeta-gliadin. Furthermore, the
      allergenicity of native total gliadin (alphabeta, gamma, omega) was analyzed by
      means of ImmunoCAP. RESULTS: One cDNA clone was identified as an alphabeta
      gliadin. Serum IgE antibodies to the recombinant allergen were found in 12% of
      bakers with occupational asthma. Of the asthmatic bakers, 33% showed
      sensitization to native total gliadin; 4% of them had negative results on routine
      IgE testing with wheat extract. CONCLUSIONS: Gliadins represent a newly
      discovered family of inhalable allergens in baker's asthma. This finding
      demonstrates that water-insoluble proteins might also represent causative
      allergens.

PMID- 18036648
TI  - Toll-like receptor 9 suppression in plasmacytoid dendritic cells after IgE
      dependent activation is mediated by autocrine TNF-alpha.
AB  - BACKGROUND: Functional significance for the alphagamma(2) variant of the high
      affinity IgE receptor (FcepsilonRI) reportedly expressed on human dendritic cell
      subtypes remains poorly understood. Studies show that immature plasmacytoid
      dendritic cells (pDCs) secrete large quantities of TNF-alpha and IL-6 when
      directly stimulated with anti-IgE antibody. This mode of activation, however,
      reduces Toll-like receptor 9 (TLR9) expression in pDCs and their ability to mount
      an IFN-alpha response when subsequently activated with oligodeoxynucleotide
      containing CpG. OBJECTIVE: To investigate the mechanisms underlying this IgE
      dependent suppression of TLR9 and innate immune responsiveness in pDCs by
      focusing on autocrine cytokine responses. METHODS: pDCs were isolated from blood
      by using blood dendritic cell antigen 4 selection. Cytokine responses to anti-IgE
      antibody-dependent and/or CpG-dependent stimulation were measured by using ELISA.
      TLR9 expression was determined by using quantitative RT-PCR and Western blotting.
      RESULTS: The time required for downregulating TLR9 expression in pDCs after anti
      IgE stimulation correlated with the induction and duration of TNF-alpha secreted
      by these cells. Pretreatment of pDCs with recombinant TNF-alpha (but not IL-6 or
      IL-10) markedly suppressed TLR9 expression. Functional response to CpG (ie, IFN
      alpha induction) was also inhibited with TNF-alpha pretreatment (inhibitory
      concentration(50) = approximately 200 pg/mL). Finally, an antibody that
      neutralizes TNF-alpha activity completely restored TLR9 expression during anti
      IgE stimulation and significantly improved IFN-alpha secretion on subsequent
      activation with CpG. CONCLUSION: Autocrine TNF-alpha secretion resulting from
      IgE/FcepsilonRI-dependent activation plays a critical role in suppressing TLR9
      dependent responses in pDCs that normally promote T(H)1 activity.

PMID- 18036647
TI  - Targeting TNF-alpha: a novel therapeutic approach for asthma.
AB  - Approximately 5% to 10% of patients with asthma have severe disease that is
      refractory or poorly responsive to inhaled corticosteroid therapy. These patients
      represent an important unmet clinical need because they experience considerable
      morbidity and mortality and consume a disproportionately large amount of health
      care resources. TNF-alpha is a proinflammatory cytokine that has been implicated
      in many aspects of the airway pathology in asthma. Evidence is emerging to
      suggest that it might play an important role in severe refractory disease. The
      development of novel TNF-alpha antagonists has allowed us to test the role of
      this cytokine in vivo. Preliminary studies have demonstrated an improvement in
      asthma quality of life, lung function, and airway hyperresponsiveness and a
      reduction in exacerbation frequency in patients treated with anti-TNF-alpha
      therapy. However, there is marked heterogeneity in response, suggesting that
      benefit is likely to be reserved to a small subgroup. Importantly, where efficacy
      is reported, this also needs to be considered in the context of concerns about
      the safety of anti-TNF-alpha therapies. Therefore the challenge for clinicians is
      to evaluate the risk/benefit ratio of these therapies in individual patients with
      asthma.

PMID- 18036649
TI  - Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase regulate
      induction of Mcl-1 and survival in glucocorticoid-treated human neutrophils.
AB  - BACKGROUND: Glucocorticoids have been shown to inhibit human neutrophil
      apoptosis, with implications that this might help accentuate neutrophilic
      inflammation. OBJECTIVE: The aim of this study was to investigate the molecular
      mechanisms involved in glucocorticoid-mediated inhibition of primary human
      neutrophil apoptosis. METHODS: Primary human neutrophils were isolated from
      peripheral blood of healthy volunteers and cultured in vitro with dexamethasone.
      RESULTS: Here we confirm that dexamethasone, a classical glucocorticoid,
      significantly inhibited apoptosis of primary human neutrophils. This inhibition
      was not dependent on transrepression of proapoptotic molecules but was associated
      with induction of antiapoptotic Mcl-1. Remarkably, glucocorticoid-mediated
      enhancement of Mcl-1 and survival were significantly suppressed by pharmacologic
      inhibition of p38 mitogen-activated protein kinase or phosphatidylinositol 3
      kinase. Inhibition of the above kinases also blocked glucocorticoid-induced
      maintenance of mitochondrial transmembrane potential and suppression of caspases.
      CONCLUSION: Phosphatidylinositol 3-kinase and p38 mitogen-activated protein
      kinase are protein kinases that regulate the prosurvival effect of
      glucocorticoids on human neutrophils.

PMID- 18036650
TI  - Inhibition of FcepsilonRI-dependent mediator release and calcium flux from human
      mast cells by sialic acid-binding immunoglobulin-like lectin 8 engagement.
AB  - BACKGROUND: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a
      family of glycan-binding inhibitory receptors, and among them, Siglec-8 is
      selectively expressed on human eosinophils, basophils, and mast cells. On
      eosinophils, Siglec-8 engagement induces apoptosis, but its function on mast
      cells is unknown. OBJECTIVE: We sought to study the effect of Siglec-8 engagement
      on human mast cell survival and mediator release responses. METHODS: Human mast
      cells were generated from CD34+ precursors. Apoptosis was studied by using flow
      cytometry. Mast cell mediator release or human lung airway smooth muscle
      contraction was initiated by FcepsilonRI cross-linking with or without
      preincubation with Siglec-8 or control antibodies, and release of mediators was
      analyzed along with Ca++ flux. RBL-2H3 cells transfected with normal and mutated
      forms of Siglec-8 were used to study how Siglec-8 engagement alters mediator
      release. RESULTS: Siglec-8 engagement failed to induce human mast cell apoptosis.
      However, preincubation with Siglec-8 mAbs significantly (P < .05) inhibited
      FcepsilonRI-dependent histamine and prostaglandin D(2) release, Ca++ flux, and
      anti-IgE-evoked contractions of human bronchial rings. In contrast, release of IL
      8 was not inhibited. Siglec-8 ligation was also shown to inhibit beta
      hexosaminidase release and Ca++ flux triggered through FcepsilonRI in RBL-2H3
      cells transfected with full-length human Siglec-8 but not in cells transfected
      with Siglec-8 containing a tyrosine to phenylalanine point mutation in the
      membrane-proximal immunoreceptor tyrosine-based inhibitory motif domain.
      CONCLUSION: These data represent the first reported inhibitory effects of Siglec
      engagement on human mast cells.

PMID- 18036651
TI  - Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal
      Langerhans cells.
AB  - BACKGROUND: Despite high bacterial colonization, acute infections are rare in the
      oral mucosa, implicating tolerogenic predominance. Bacterial antigens like LPSs
      are recognized by innate immunity receptors such as Toll-like receptor 4 (TLR4),
      associated with LPS receptor (CD14). OBJECTIVES: Toll-like receptor 4 agonist
      monosphoryl lipid A has been successfully used as adjuvant in subcutaneous
      immunotherapy, suggesting reinforcement of allergen-specific tolerance. Recently
      sublingual immunotherapy (SLIT) has been shown to be an effective alternative to
      subcutaneous immunotherapy. We observed CD14 expression on human oral Langerhans
      cells (oLCs), representing a major target of SLIT. However, not much is known
      about TLR4 expression and its effect on oLCs. METHODS: Cell suspensions were
      obtained by trypsinization of human oral mucosa and analyzed by flow cytometry,
      RT-PCR, cytometric bead arrays, ELISA, and mixed lymphocyte reactions. RESULTS:
      We could show that oLCs express TLR4, and its ligation by monosphoryl lipid A
      upregulated expression of coinhibitory molecules B7-H1 and B7-H3 while surface
      expression of costimulatory molecule CD86 was concomitantly decreased.
      Furthermore, TLR4 ligation on oLCs increased their release of the anti
      inflammatory cytokine IL-10 and decreased their stimulatory capacity toward T
      cells. Moreover, TLR4-ligation on oLCs induced IL-10, TGF-beta1, Forkhead box
      protein 3, IFN-gamma, and IL-2 production in T cells. CONCLUSION: In view of
      these data, TLR4-ligation on oLCs might not only play a role in pathogen
      recognition for efficient immunity but also contribute to the tolerogenic state
      predominating in the oral cavity.

PMID- 18036652
TI  - Lipid transfer protein-linked hazelnut allergy in children from a non
      Mediterranean birch-endemic area.
AB  - BACKGROUND: Hazelnut allergy in birch pollen-exposed areas is usually due to
      cross-reactivity (Cor a 1 and 2) and is usually mild in nature (oral allergy). In
      areas without birches, severe reactions are more prevalent and linked to
      sensitization to the lipid transfer protein (LTP) Cor a 8. OBJECTIVE: We sought
      to investigate whether sensitization to LTP plays a role in more severe
      (objective) hazelnut-induced symptoms in children from a birch-endemic area.
      METHODS: Sensitization to Cor a 8, Cor a 2, Cor a 1, and Bet v 1 was determined
      by means of RASTs and immunoblotting in hazelnut-sensitized children with (n = 8)
      and without (n = 18) objective reactions during double-blind, placebo-controlled
      food challenges. Additionally, samples from 191 hazelnut-sensitized nonchallenged
      children were analyzed. RESULTS: Children with objective reactions during double
      blind, placebo-controlled food challenge had higher IgE titers to hazelnut (P <
      .001) and recognized more allergens on immunoblotting (P = .001) than those
      without such reactions. All children with objective symptoms were sensitized to
      Cor a 8 (0.51-23.3 IU/mL) compared with only 1 child without objective reactions
      (0.90 IU/mL). In a multivariate analysis only IgE against Cor a 8 remained as an
      independent risk factor (undefined odds ratio; P < .0001). In the group of
      nonchallenged children (n = 191), the prevalence of LTP sensitization was greater
      than 30%. Unexpectedly, sensitization to Cor a 1 was observed in children not
      sensitized to Bet v 1. CONCLUSION: Sensitization to hazelnut LTP is a risk factor
      for objective symptoms in children from a birch-endemic area.

PMID- 18036653
TI  - Lack of risk of transmission of caprine arthritis-encephalitis virus (CAEV) after
      an appropriate embryo transfer procedure.
AB  - The aim of this study was to demonstrate that embryo transfer can be used to
      produce CAEV-free kids from CAEV-infected biological mothers when appropriate
      procedure is implemented. Twenty-eight goats that had tested positive for CAEV
      using PCR on vaginal secretions were used as embryo donors. Embryos with intact
      ZP were selected and washed 10 times; they were then frozen and used for transfer
      into CAEV-free recipient goats. Nineteen of the 49 recipient goats gave birth,
      producing a total of 23 kids. Three blood samples were taken from each recipient
      goat, 10 days before, during, and 10 days after parturition; these were tested
      for CAEV antibodies using ELISA and for CAEV proviral DNA using PCR. The mothers
      were then euthanized. Tissue samples were taken from the lungs, udder, and
      retromammary and prescapular lymph nodes. The kids were separated from their
      mothers at birth. Seven of them died. At 4 months of age, 16 kids were subjected
      to drug-induced immunosuppression. Blood samples were taken every month from
      birth to 4 months of age; samples were then taken on days 15, 21, and 28 after
      the start of the immunosuppressive treatment. The kids were then euthanized and
      tissue samples taken from the carpal synovial membrane, lung tissue, prescapular
      lymph nodes, inguinal and retromammary lymph nodes, and uterus. All samples from
      the 19 recipient goats and 23 kids were found to be negative for CAEV antibodies
      and/or CAEV proviral DNA. Under acute conditions for infection this study clearly
      demonstrates that embryo transfer can be safely used to produce CAEV-free
      neonates from infected CAEV donors.

PMID- 18036654
TI  - Vasoactive factors and hemodynamic mechanisms in the pathophysiology of portal
      hypertension in cirrhosis.
AB  - Portal hypertension is primarily caused by the increase in resistance to portal
      outflow and secondly by an increase in splanchnic blood flow, which worsens and
      maintains the increased portal pressure. Increased portal inflow plays a role in
      the hyperdynamic circulatory syndrome, a characteristic feature of portal
      hypertensive patients. Almost all the known vasoactive systems/substances are
      activated in portal hypertension, but most authors stress the pathogenetic role
      of endothelial factors, such as COX-derivatives, nitric oxide, carbon monoxide.
      Endothelial dysfunction is differentially involved in different vascular beds and
      consists in alteration in response both to vasodilators and to vasoconstrictors.
      Understanding the pathogenesis of portal hypertension could be of great utility
      in preventing and curing the complications of portal hypertension, such as
      esophageal varices, hepatic encephalopathy, ascites.

PMID- 18036655
TI  - Binding of daunorubicin to human serum albumin using molecular modeling and its
      analytical application.
AB  - This study was designed to examine the interaction of daunorubicin with human
      serum albumin (HSA) for the first time by fluorescence spectroscopy in
      combination with UV absorption and molecular modeling under simulative
      physiological conditions. The quenching mechanism was suggested to be static
      quenching according to the fluorescence measurement and the linearity of
      Scatchard plot indicated that daunorubicin bound to a single class of binding
      sites on HSA. The thermodynamic parameters, enthalpy change (DeltaH) and entropy
      change (DeltaS) were calculated to be -16.13 kJ/mol and 27.86 J/(molK), according
      to the Vant'Hoff equation. These data suggested that hydrophobic interaction was
      the predominant intermolecular forces stabilizing the complex, which was in good
      agreement with the results of molecular modeling study. In addition, the effects
      of common ions on the binding constant of daunorubicin-HSA complex were also
      discussed at room temperature. Moreover, the synchronous fluorescence technique
      was successfully employed to determine the total proteins in serum, urine and
      saliva samples at room temperature under the optimum conditions with a wide
      linear range and satisfactory results.

PMID- 18036656
TI  - XRD studies of beta-chitin from squid pen with calcium solvent.
AB  - The crystalline structure of beta-chitin from squid pen was investigated by X-ray
      diffraction (XRD). The purified beta-chitin was prepared from bigfin reefsquid
      pen. beta-Chitin was treated with saturated calcium chloride dihydrate/alchohol
      (CaCl(2).2H(2)O/MeOH) solvent system at different conditions for XRD studies. The
      change of crystallinity of beta-chitin from squid pen was studied by using the
      fiber photographs on imaging plates. The results showed that the diffraction peak
      (010) was shifted. It means that the lattice plane (010) interplanarilly spreaded
      to 3.4A, when the squid pen was washed with water after treatment of Ca solvent.
      Furthermore, when the squid pen was dried after treatment of Ca solvent and
      washing with water, interplanar spacing of (010) inversely shrank to 1.1A. These
      results suggested that Ca solvent especially influences the plane (010) of beta
      chitin structure.

PMID- 18036657
TI  - Bone marrow necrosis complicating post-transplant lymphoproliferative disorder:
      resolution with rituximab.
AB  - Bone marrow necrosis is a rare cause of bone marrow failure. Malignancy is the
      most frequent cause of bone marrow necrosis. Among malignancies, non-Hodgkin
      lymphoma (NHL) accounts for 10% of cases of bone marrow necrosis. Virtually all
      reported cases of NHL-associated bone marrow necrosis have developed in
      immunocompetent hosts. We report on a case of bone marrow necrosis complicating
      post-transplant lymphoproliferative disorder (PTLD) and resolving after rituximab
      monotherapy. This case report provides the first evidence of (i) bone marrow
      necrosis as a complication of PTLD; (ii) rapid resolution of NHL-associated bone
      marrow necrosis after rituximab treatment.

PMID- 18036659
TI  - Molecular and functional characterization of goldfish (Carassius auratus L.)
      transforming growth factor beta.
AB  - Transforming growth factor beta (TGF-beta) is a pleiotropic cytokine with
      important roles in the regulation of cell proliferation, differentiation,
      survival, migration, activation and de-activation. It is one of the first
      cytokines released during an immune response and plays a strong immunomodulatory
      role in the activation and subsequent de-activation of macrophages and other
      immune cells. TGF-beta is a highly conserved molecule, and members of the TGF
      superfamily can be found in organisms as evolutionarily distant as arthropods. In
      this manuscript, we described the identification of a goldfish TGF-beta molecule,
      which was highly expressed in the skin, kidney and spleen of the goldfish and its
      expression was up-regulated in macrophages treated with LPS or recombinant
      goldfish TNF-alpha. Goldfish TGF-beta shared a high amino acid identity with, and
      was phylogenetically related to, TGF-beta1 of other teleost fish, birds,
      amphibians and mammals. Recombinant goldfish TGF-beta (rTGF-beta) induced the
      proliferation of a goldfish fibroblast cell line (CCL71) in a dose-dependent
      manner. In addition, rTGF-beta down-regulated the nitric oxide response of TNF
      alpha-activated macrophages. This is the first report of teleost TGF-beta
      function in an ectothermic vertebrate.

PMID- 18036660
TI  - WHO-IUIS Nomenclature Subcommittee for immunoglobulins and T cell receptors
      report August 2007, 13th International Congress of Immunology, Rio de Janeiro,
      Brazil.

PMID- 18036658
TI  - Immunoglobulin superfamily members play an important role in the mosquito immune
      system.
AB  - Immunoglobulin superfamily (IgSF) proteins are known for their ability to
      specifically recognize and adhere to other molecules, mediating cell-surface
      reception and pathogen recognition. Mammalian IgSF proteins such as antibodies
      are among the best characterized molecules of the immune system; in contrast, the
      involvement of invertebrate IgSF members in immunity has not been broadly
      studied. Analysis of the predicted Anopheles gambiae transcriptome identified 138
      proteins that have at least one immunoglobulin domain. Challenge with Plasmodium,
      Gram-negative or Gram-positive bacteria resulted in significant regulation of 85
      IgSF genes, indicating potential roles for these molecules in infection responses
      and immunity. Based on sequence and expression data, six infection-responsive
      with immunoglobulin domain (IRID 1-6) genes were chosen and functionally
      characterized with regard to their role in innate immunity. Reverse-genetic gene
      silencing assays showed IRID3, IRID5 and IRID6 contribute to viability upon
      bacterial infection while IRID4 and IRID6 are involved in limiting Plasmodium
      falciparum infection.

PMID- 18036661
TI  - Methods for behavioral testing of spinal cord injured rats.
AB  - Behavioral outcome in rats with spinal cord injury (SCI) is the most important
      factor for evaluating the extent of injury and treatment efficacy. For this
      purpose, a number of behavioral testing methods can be used. In this review, 35
      individual locomotor, motor, sensory, sensory-motor, autonomic or
      electrophysiological behavioral tests, their weaknesses and strengths, testing
      conditions, the need for habituation, pre-training and/or food deprivation,
      methods for increasing the animals' skills, systematic testing protocols and
      methods for selecting the proper behavioral tests for particular injury models
      are discussed on the basis of a retrospective analysis of scientific studies
      published from 1995 to 2007. This review is primarily targeted towards
      researchers outside the field or to researchers new to the field of SCI.

PMID- 18036662
TI  - Baron Kelvin of Largs: an economical engineer.
AB  - William Thomson--honoured as Baron Kelvin of Largs--was Victorian Britain's most
      famous physicist, especially celebrated for laying the trans-Atlantic telegraph
      cable. As well as profiting financially from his many engineering projects,
      Kelvin introduced influential theories about energy and electromagnetism, all
      strongly coloured by his industrial experiences and the thrifty attitudes of
      Scottish Christians. Never accepting radioactivity as an additional energy source
      to the sun, he insisted that the Earth's life span was far too short for
      evolution to have taken place.

PMID- 18036663
TI  - The duck toll like receptor 7: genomic organization, expression and function.
AB  - TLR7 and TLR8 are triggered by antiviral compounds and single-stranded RNA, and
      are implicated in the immune response to viruses such as influenza. Chickens have
      a functional TLR7 gene and a genomic disruption in TLR8. PCR evidence suggested
      that the TLR8 disruption existed in galliform birds, but not anseriform birds. We
      investigated this due to the different susceptibility of ducks and chickens to
      influenza. We sequenced a 39 kb duck genomic clone spanning the TLR7/8 locus.
      Similar to chicken, we detect only fragments of the TLR8 gene in the region
      downstream of TLR7. Duck TLR7 shares only 85% amino acid identity to chicken
      TLR7, differing primarily in the ligand-binding LRR domains. TLR7 transcripts
      were most abundantly expressed in duck spleen, bursa and lung. Duck splenocytes
      respond to TLR7 agonists with upregulation of mRNA encoding proinflammatory
      cytokines and IFN alpha, with imiquimod eliciting the greatest response. TLR7
      expression in lung, and upregulation of IFN alpha by TLR7 agonists, not typically
      seen in chickens, could contribute significantly to the antiviral defense of
      ducks. These differences in TLR7 function, not genomic organization, may
      contribute to the differential susceptibility of avian species to viral
      infection.

PMID- 18036664
TI  - High plasma IgE levels within the Scandinavian wolf population, and its
      implications for mammalian IgE homeostasis.
AB  - Immunoglobulin E (IgE) serves as an important link between innate and adaptive
      immunity through its ability to bind high affinity receptors on mast cells and
      basophils. Large differences in IgE levels may here affect this important link,
      and IgE levels in natural non-domestic animal populations may therefore be very
      informative concerning the levels of IgE that this system have been balanced
      against during recent mammalian evolution. However, very few such studies have
      been performed. Here, we present an analysis of total IgE levels in 65
      Scandinavian wolves: 57 free living (wild), and 8 wolves in captivity (Zoo). The
      57 wild wolves correspond to approximately 30% of the entire wolf population in
      Sweden and Norway and thus represent a large fraction of the entire population,
      making this a unique sample from a wild canine population. The median IgE level
      in these wolves was 67 microg/ml, which is approximately twice the level seen in
      domestic dogs and more than 100 times the levels in non-atopic humans. The
      collected information from domestic and wild populations now indicate that the
      very low IgE levels observed in man and laboratory rodents are most likely an
      effect of a life in a relatively parasite free environment, and that total IgE
      levels under maximally stimulatory (normal) conditions may reach 100-200
      microg/ml.

PMID- 18036665
TI  - Corynebacterium minutissimum bacteremia and meningitis: a case report and review
      of literature.
AB  - Corynebacterium minutissimum, the causative agent of erythrasma, is a gram
      positive, non-spore forming, aerobic or facultative anaerobic bacillus. It has
      rarely been associated with extracutaneous disease, since its description in
      1961. A computerized medline search for review of literature was performed. To
      our knowledge, there have been 18 cases of C. minutissimum infections that caused
      conditions other than erythrasma. These include reports of cases of abscess
      formation, intravascular catheter-related bacteremias, ophthalmologic
      involvement, endocarditis, peritonitis, cutaneous granulomas, pyelonephritis in
      an infant and primary bacteremia with underlying hematologic malignancy. We
      report a rare case of bacteremia and meningitis due to C. minutissimum
      successfully treated with intravenous ampicillin.

PMID- 18036666
TI  - Choosing the shortest way to Mum: auditory guided rotation in 6- to 9-month-old
      infants.
AB  - The purpose of this study was to investigate the use of auditory information for
      rotation of the shortest way in twelve 6- to 9-month-old sighted infants.
      Behavior was manipulated by means of an auditory stimulus presented in four
      different directional angles (90 degrees , 112.5 degrees , 135 degrees , and
      157.5 degrees ) to the right and to the left behind the infants, and in one non
      directional angle (180 degrees ). Infants lay in a prone position and had
      magnetic trackers fastened to the head and body which measured their rotation
      direction and angular velocity. The results showed that infants not only
      consistently chose the shortest over the longest way, but also rotated with a
      higher peak angular velocity as the angle to be covered between themselves and
      the goal increased. The results did not show significant preferences for one
      particular rotation direction. The study can contribute to the understanding of
      the auditory system as a functional listening system where auditory information
      is used as a perceptual source for prospectively guiding behavior in the
      environment.

PMID- 18036667
TI  - The timing of verbal/vocal communications between mothers and their infants: a
      longitudinal cross-cultural comparison.
AB  - Early dialogues between parent and child constitute an important factor for the
      acquisition of culture and hence verbal interaction is considered to be a
      universal parenting system. Parenting strategies and socialization practices are
      strongly influenced by the cultural conception of the self, prototypically
      defined as the model of independence and interdependence. Our study focuses on
      the temporal organization of spontaneous verbal/vocal behavior of 20 German
      middle-class and 28 Cameroonian Nso mother-infant dyads. The infants and their
      mothers were observed weekly in a 5 min free-play interaction scene from 0 to 3
      months of age. We hypothesized to find different amounts of vocalization time,
      synchronous vocalizations, and contingent maternal responses in the verbal/vocal
      patterns of the two samples. The findings indicate cross-cultural differences in
      the temporal structure of verbal/vocal interactions already during the first
      three months of life, reflecting underlying differences in the culture-specific
      modes of verbal interaction.

PMID- 18036668
TI  - Factors affecting infants' manual search for occluded objects and the genesis of
      object permanence.
AB  - Two experiments systematically examined factors that influence infants' manual
      search for hidden objects (N=96). Experiment 1 used a new procedure to assess
      infants' search for partially versus totally occluded objects. Results showed
      that 8.75-month-old infants solved partial occlusions by removing the occluder
      and uncovering the object, but these same infants failed to use this skill on
      total occlusions. Experiment 2 used sound-producing objects to provide a
      perceptual clue to the objects' hidden location. Sound clues significantly
      increased the success rate on total occlusions for 10-month-olds, but not for
      8.75-month-olds. An identity development account is offered for why infants
      succeed on partial occlusions earlier than total occlusions and why sound helps
      only the older infants. We propose a mechanism for how infants use object
      identity as a basis for developing a notion of permanence. Implications are drawn
      for understanding the dissociation between looking time and search assessments of
      object permanence.

PMID- 18036669
TI  - Glutamate-dopamine-GABA interactions in the aging basal ganglia.
AB  - The study of neurotransmitter interactions gives a better understanding of the
      physiology of specific circuits in the brain. In this review we focus mostly on
      our own results on the interaction of the neurotransmitters glutamate, dopamine
      and GABA in the basal ganglia during the normal process of aging. We review first
      the studies on the action of endogenous glutamate on the extracellular
      concentrations of dopamine and GABA in the neostriatum and nucleus accumbens
      during aging. It was found that there exists an age-related change in the
      interaction of glutamate, dopamine and GABA and that these effects of aging
      exhibit a dorsal-to-ventral pattern of effects with no changes in the dorsal
      parts (dorsal striatum) and changes in the most ventral parts (nucleus
      accumbens). Second we reviewed the data on the effects of different ionotropic
      and metabotropic glutamate receptor agonists on the extracellular concentrations
      of dopamine and GABA in the nucleus accumbens. The results obtained clearly show
      the different contribution of each glutamate receptor subtype in the age-related
      changes produced on the interaction of glutamate, dopamine and GABA in this area
      of the brain. Third the effects of an enriched environment on the action of AMPA
      and NMDA-receptor agonists in the nucleus accumbens of rats during aging are also
      evaluated. Finally, and since the nucleus accumbens has been suggested to play a
      role in emotion and motivation and also motor behaviour, we speculated on the
      possibility of a specific contribution for the different glutamatergic pathways
      terminating in the nucleus accumbens and their interaction with a decreased
      dopamine playing a relevant role in motor behaviour during aging.

PMID- 18036670
TI  - Isolation by phage display of recombinant antibodies able to block adherence of
      Escherichia coli mediated by the K99 colonisation factor.
AB  - K99 fimbriae are important for intestinal colonisation by bovine strains of
      enterotoxigenic Escherichia coli. The mode of action of this colonisation factor
      is well understood and specific immune responses are protective. K99 was
      therefore chosen for this study as a model to test if antibodies with anti
      adhesion activity could be isolated from recombinant libraries using phage
      display techniques. Potentially, this strategy could be used to understand better
      the action of bacterial colonisation factors and aid the design of therapies
      (e.g. vaccines, purified protein products or bacteria bearing colonisation
      blocking antibodies) to inhibit bacterial adherence. The major fimbrial subunit
      from K99, FanC, was purified from a clinical E. coli isolate. The protein was
      coated to plastic immunotubes and used as a target for selection of antibodies
      from the Tomlinson I and J libraries of single chain (scFv) antibodies. Clones
      able to recognise K99 were isolated by iterative rounds of binding, elution and
      amplification. scFv antibodies chosen from the resulting panel were purified and
      their specificity confirmed by ELISA. Pre-incubation of several scFvs with
      bacteria expressing K99 fimbriae inhibited the agglutination of erythrocytes.
      Further investigation by microscopy confirmed that when E. coli expressing K99
      were exposed to scFv antibodies, the binding of bacteria to erythrocytes was
      blocked with high efficiency. The study showed that recombinant antibodies were
      able to block the action of a bacterial colonisation factor and hence that phage
      display techniques might be applied to the identification of less well
      characterised virulence factors and the analysis of their structure and function.

PMID- 18036671
TI  - Effect of four adjuvants on immune response to F4 fimbriae in chickens.
AB  - IgG antibody response in chickens immunized with F4 fimbriae extracted from local
      enterotoxigenic Escherichia coli (ETEC) strain was studied during a 98-day
      immunization period for comparing the efficacy of four adjuvants: Freund'
      adjuvant, Quil A (QA), propolis and extract from Cochinchina momordica seed
      (ECMS). For this purpose, chickens were immunized with F4 fimbriae alone or
      combined with one of the above adjuvants on days 1 and 21. IgG antibody levels in
      serum and egg yolk (by ELISA) were measured on days 0, 7, 14, 21, 28, 35, 42, 49,
      56, 70, 84 and 98. The egg production of each group was also determined during
      days 1-7 and the following four weeks. The results showed that QA could enhance
      antibody titre, as good or almost as good as Freund's adjuvant, whereas the
      titres of ECMS and propolis groups were relatively lower, with the overall order:
      Freund's adjuvant>QA>ECMS>propolis both in serum and egg yolk. However, the
      significant decrease of egg production was merely observed in the Freund's
      adjuvant group. It is concluded that the four adjuvants tested can stimulate
      immune response to F4 fimbriae in chickens, with Freund's adjuvant giving the
      best results, followed by QA.

PMID- 18036672
TI  - Animal models of highly pathogenic RNA viral infections: hemorrhagic fever
      viruses.
AB  - A diverse group of highly pathogenic RNA viruses cause a severe multisystemic
      illness in humans commonly referred to as viral hemorrhagic fever (VHF). Although
      they can vary widely in clinical presentation, all VHFs share certain features
      that include intense fever, malaise, bleeding and shock. Effective antiviral
      therapies for most of the VHFs are lacking. Complicating development of
      intervention strategies is the relative infrequency and unpredictability of VHF
      outbreaks making human clinical trials extremely challenging or unfeasible.
      Therefore, animal models that can recapitulate human disease are essential to the
      development of effective antivirals and vaccines. In general, a good animal model
      of VHF will demonstrate systemic dispersion of the virus through infection of
      mononuclear phagocytes and dendritic cells, which induces the release of
      inflammatory mediators that increase vascular permeability and facilitate
      coagulation. The culmination of this process leads to significant loss of plasma
      volume and terminal hypovolemic shock. Although it is clear that nonhuman primate
      models are the most faithful to human disease, the more accessible and less
      costly rodent models, including those based on infection with related surrogate
      viruses, can reproduce certain components of VHF and can serve as suitable
      preclinical models for initial development of effective countermeasures. Such
      models are sufficient for testing of drugs that directly block viral replication,
      but may be inadequate for evaluating therapies that depend for their success on
      the activation or inhibition of host responses.

PMID- 18036673
TI  - Individual responses to novelty are associated with differences in behavioral and
      neurochemical profiles.
AB  - Experimental animals can be differentiated on the basis of their horizontal or
      vertical activity to high responders (HR) and low responders (LR) upon exposure
      to a novel environment. These individual differences have been associated with
      behavioral and neurobiological differences in a number of experimental procedures
      used for studying sensitivity to psychostimulants, anxiety, depression, and
      cognitive function. In the present study, we differentiated the rats to HR and LR
      based on their vertical activity upon exposure to a novel environment.
      Additionally, we ascertained whether HR and LR rats differ in a battery of tests
      such as passive avoidance (PA), object recognition (OR), and the water-maze (WM)
      that provide indices for cognitive function and the forced swim test (FST), an
      animal model of affective responsivity and antidepressant-like activity.
      Potential differences in neurochemical indices between the two phenotypes were
      also examined. HR rats displayed impaired non-spatial object recognition memory,
      but enhanced spatial performance, as compared to LR rats. FST induced "depressive
      like" symptoms in both phenotypes that were differently manifested in HR versus
      LR rats. Neurochemical findings revealed distinct differences in serotonergic and
      dopaminergic activity in the striatum and the prefrontal cortex of HR as compared
      to LR rats. The above results show that HR and LR rats exhibit important
      differences in a battery of tests related to cognitive performance or affective
      responsivity, which may be associated with differences in certain neurobiological
      parameters.

PMID- 18036674
TI  - Community-level microalgal toxicity assessment by multiwavelength-excitation PAM
      fluorometry.
AB  - In ecotoxicological studies involving community-level investigations, rapid and
      multiparametric fluorescence-based methods may provide substantial advantages
      over traditional methods used for structural and functional community analysis.
      Therefore, multiwavelength-excitation pulse-amplitude modulated (PAM) fluorometry
      was applied in this study to assess long-term changes in periphyton community
      structure, short-term effects on periphyton functioning (photosynthesis) and
      pollution induced community tolerance (PICT). For inter-calibration, periphyton
      structure was evaluated by chemotaxonomic analysis of accessory pigments and a
      four-wavelength-excitation PAM fluorometer. Short-term effects of herbicides were
      evaluated by fluorescence quenching analysis and (14)C-incorporation as a proxy
      of primary production. Subsequently, the method was applied to assess structural
      and functional changes in periphyton communities after isoproturon exposure for
      14 and 26 days, respectively. Results showed good correlation of the PAM
      fluorescence-based measurements with traditional methods for biofilms in the
      initial colonisation phase for structural and functional parameters. However, for
      biofilms older than 9 weeks PAM fluorescence may underestimate biomass.
      Multiwavelength-excitation PAM fluorometry showed good correlation with marker
      pigment concentrations indicating that this method provides a reliable estimate
      of the community structure. PAM fluorometry was able to quantify changes of
      biomass and follow relative shifts in class composition of biofilms under
      exposure of isoproturon. Short-term tests based on the quantification of the
      inhibition of the effective quantum yield revealed a concentration-dependent
      increase of PICT. The observation of two succession phases of the biofilms after
      14 and 26 days of growth, respectively, revealed that sensitivity of biofilms
      decreased with increasing age and biomass, respectively, but PICT remained a
      characteristic parameter of exposed communities in a concentration-dependent
      relationship. In conclusion, multiwavelength-excitation PAM fluorometry has
      considerable potentials in multispecies and multiparameter assessment of toxic
      effects on community level in terms of (1) a combined and rapid evaluation of
      structural and functional parameters in parallel, (2) screening of trends over
      time, (3) observing effects in replication and (4) being non-destructive. The
      approach therefore provides a perspective for a better understanding of community
      level effects as species interactions in terms of PICT and therefore a higher
      ecological realism in risk assessment of toxicants.

PMID- 18036675
TI  - Mastitis unmasks Brugada syndrome.
AB  - The Brugada syndrome is an important cause of sudden cardiac death primarily
      among males without structural heart disease. Although not widely known, it may
      be unmasked by an acute febrile illness. An association between mastitis and
      Brugada syndrome has not been previously reported. We describe an 18-year-old
      postpartum female who developed mastitis, fever, and syncope. Electrocardiography
      revealed type 1 Brugada pattern, which disappeared once her fever resolved.
      Although the role of pregnancy in this syndrome is unknown, clinicians should be
      aware that fever may precipitate Brugada syndrome among peripartum women.

PMID- 18036677
TI  - Role of dynamic intraventricular obstruction and protective effect of beta
      blocking therapy in left ventricular apical ballooning syndrome: a case report.
AB  - This paper reports on a 58-year old woman with left ventricular apical ballooning
      syndrome (LVABS), who after interruption of beta-blocking therapy had a
      recurrence of symptoms and developed a severe dynamic left ventricular
      obstruction (LV-DYN-O) during sympathetic stimulation with dobutamine.

PMID- 18036679
TI  - Treatment of Tako-tsubo cardiomyopathy.

PMID- 18036678
TI  - Metabolic syndrome determinants in an urban population from Brazil: social class
      and gender-specific interaction.
AB  - INTRODUCTION: The metabolic syndrome (MS) is characterized by multiple
      cardiovascular risk factors such as central obesity, arterial hypertension,
      dyslipidemia and hyperinsulinemia and is associated with a higher incidence of
      cardiovascular events and mortality. The aim of the present work is to describe
      the prevalence of MS in an urban population from a highly admixed developing
      country and to characterize the different correlations between this diagnosis,
      cardiovascular risk factors and demographic variables distributed in this
      population. MATERIALS AND METHODS: A cross-sectional study of risk factors for
      cardiovascular diseases was performed in the urban population of Vitoria, Brazil
      (n=1507). Major cardiovascular risk factors such as smoking habits, alcohol
      intake, amount of physical activity, diabetes and hypertension were inquired.
      Blood biochemical assays were performed by standard techniques in 12 h fasting
      blood sample and Metabolic Syndrome (MS) was characterizes following the ATP III
      criteria. RESULTS: The analysis of 1507 individuals showed a 25.43% general
      prevalence of MS without any significant difference between sexes, but a clear
      relation of the prevalence with progressing age (p=<0.0001). Even though both
      sexes showed similar prevalence rates, distribution of risk factors that defined
      MS was different between men and women, with the prevalence of hypertension,
      fasting hyperglycemia and hypertriglyceridemia being higher in men. Race was not
      an important risk factor for MS in this population as opposed to social economic
      class that was highly associated with the risk of MS in women as their social
      class was lower, but not in men. CONCLUSION: This cross-sectional study from a
      large urban population in Brazil showed a high general prevalence of MS (25.4%),
      which is increased as the population becomes older (especially in women) and
      poorer. Although prevalence was very similar in both genders, the frequency of
      components defining the syndrome varied greatly amongst them. In particular, a
      significant interaction between gender and social class was observed and may shed
      light in our understanding of the complex interplay between demographic and
      biological risk factors for metabolic syndrome.

PMID- 18036680
TI  - Acute myocardial infarction in a young patient with myocardial bridge and
      elevated levels of free triiodothyronine.
AB  - Revelation of a myocardial bridge has been described at coronary angiography. The
      pathophysiology of myocardial bridging is incompletely understood. It is
      sometimes associated with overt pathology, as well as it can just be an
      incidental finding without any significance. It has been also reported an acute
      myocardial infarction with normal coronary arteries associated with iatrogenic
      hyperthyroidism. We present a case of acute myocardial infarction in a 28-year
      old Italian man with normal coronary arteries, iatrogenic elevated levels of free
      triiodothyronine and myocardial bridge.

PMID- 18036681
TI  - Resolution of a coronary embolus by intravenous application of bivalirudin.
AB  - We report on a case of non-ST-segment myocardial infarction in the absence of
      coronary artery disease, caused by coronary embolism from the left atrial
      appendage. Due to the fact that the angiographically confirmed embolus did not
      resolve within 4 days of treatment with aspirin, clopidogrel and low molecular
      weight heparin (LMWH), we intravenously administered bivalirudin instead of LMWH
      for another 2 days and could demonstrate complete resolution of the embolus
      following this protocol. No bleeding complications or recurrence of myocardial
      ischemia occurred. Our observations may draw attention to bivalirudin therapy for
      coronary emboli, when LMWH is not effective.

PMID- 18036683
TI  - Non-invasive determination of stroke volume and cardiac output after high
      intensity playing exercise in elite female soccer players.
AB  - BACKGROUND: Stroke volume (SV) and heart rate (HR), determining cardiac output
      (CO), are crucial hemodynamic parameters determining training adoptions to
      endurance training. In soccer, aerobic power as well as intermittent exercise
      performance varies significantly among level of competition as well as playing
      position. In this study cohort study we thought to determine the hemodynamic
      changes following a standardized soccer-specific exercise in female soccer
      players at the soccer field using a portable non-invasive hemodynamic monitoring
      tool. METHODS: A non-invasive, portable continuous wave (CW) Doppler-based
      ultrasound system (USCOM, Sydney, Australia) was used to assess HR, SV, CO, and
      cardiac index (CI) using a suprasternal approach after a soccer specific exercise
      (5-vs-2-gameplay over 5 min) in an elite female soccer team of the German
      Fussball Bundesliga (15 females, 22.3+/-3.6 years). RESULTS: 30 s after the peak
      exercise the mean HR increased significantly (121+/-26 /min vs 56+/-11 /min,
      p<0.05), while SV did not change significantly (75+/-25 ml vs. 80+/-13 ml, n.s.).
      CO increased significantly (9.2+/-4.1 l/min vs. 4.5+/-1.1 l/min) as did CI (5.3+/
      2.1 l/min/m(2) vs. 2.6+/-0.6 l/min/m(2), p<0.05). CONCLUSION: Elite female soccer
      players increase cardiac output after 5-vs-2-gameplay on average to 10 l/min, in
      single cases up to 18 l/min 30 s after peak exercise. Therefore significant peak
      hemodynamic demands are encountered in soccer game play. The increase of cardiac
      output is by far more achieved by an increase of the heart rate than by stroke
      volume changes in most of the female soccer players. On field hemodynamic
      exercise testing is feasible using the USCOM in elite soccer.

PMID- 18036682
TI  - No difference in the hemodynamic response to Nordic pole walking vs. conventional
      brisk walking--a randomized exercise field test using the ultrasonic cardiac
      output monitor (USCOM).
AB  - INTRODUCTION: Nordic pole walking (NW) has gained significant attention to
      increase caloric expenditure vs. conventional walking without poles. However data
      are pending regarding the hemodynamic response of Nordic pole walking vs.
      walking. We hypothesized that NW increases cardiac output stronger than
      conventional walking at a given perceived level of physical exertion in a field
      test. METHODS: 48 participants (51+/-11 years, BMI 25+/-3) were included and
      randomised for either Nordic pole or conventional 30 min of outdoor walking.
      Heart rate (HR), stroke volume (SV), and cardiac output (CO) were determined non
      invasively using continuous CW-Doppler ultrasound (USCOM) for four times (before,
      immediately after physical exercise and after the first and third minute during
      recovery). Perceived level of exertion was 13+/-1 (NW) and 13+/-2 (walking,
      n.s.). RESULTS: Immediately after peak exercise, heart rate increased
      significantly from 74+/-9 bpm to 123+/-20 bpm (66+/-4%, NW, p<0.05) and from 73+/
      7 bpm to 137+/-30 bpm (73+/-7%, walking, p<0.05). CW-Doppler determined stroke
      volume increased from 48+/-10 ml to 59+/-24 ml (23+/-4%, p<0.05) and 45+/-20 ml
      to 50+/-13 ml (11+/-3%, p<0.05) immediately after peak exercise. Consecutive
      cardiac output increased from baseline 3.5+/-0.9 l/min to 7.3+/-3 l/min (NW) and
      from 3.4+/-1.2 l/min to 6.8+/-2.2 l/min (walking), respectively (both p<0.05).
      During recovery stroke volume significantly faster diminished within the first
      minute of recovery vs. heart rate and cardiac output in both groups. No changes
      between NW and walking were evident in hemodynamic parameters. CONCLUSION: No
      significant difference in the extent of cardiac output up-regulation between
      Nordic pole walking and walking at a given level of physical exertion was found.
      Hemodynamic field testing is feasible using the portable CW-Doppler ultrasound
      USCOM.

PMID- 18036684
TI  - Molecular inversion probes for sensitive detection of Mycobacterium tuberculosis.
AB  - Nucleic acid-based detection of Mycobacterium tuberculosis infections has the
      potential to improve the analysis of the tuberculosis epidemiology and patient
      care by increasing the specificity and sensitivity of diagnosis. One potential
      diagnostic sequence, the DR locus, is present in all isolates of M. tuberculosis
      complex bacteria. It encodes no known gene product but is useful for molecular
      typing of M. tuberculosis because of its fortuitous absence in non-tuberculosis
      strains of mycobacteria. The DR locus contains a variable number of short direct
      repeats interspersed with non-repetitive spacers and is commonly used as a target
      for the spoligotyping method, a technique based on the detection of the presence
      or absence of distinct spacers between the repeats. In this study, we attempted
      to combine the specificity of molecular inversion probe (MIP) technology with the
      sensitivity of modified pyrosequencing readout in order to detect a short
      conserved 18 bp sequence included in DR locus in 25 isolates of M. tuberculosis.
      Additional sensitivity was obtained by introducing modifications in
      pyrosequencing methodology, by these means we achieved to detect 500 fg of M.
      tuberculosis DNA.

PMID- 18036685
TI  - Nanotechnology in regenerative medicine: the materials side.
AB  - Regenerative medicine is an emerging multidisciplinary field that aims to
      restore, maintain or enhance tissues and hence organ functions. Regeneration of
      tissues can be achieved by the combination of living cells, which will provide
      biological functionality, and materials, which act as scaffolds to support cell
      proliferation. Mammalian cells behave in vivo in response to the biological
      signals they receive from the surrounding environment, which is structured by
      nanometre-scaled components. Therefore, materials used in repairing the human
      body have to reproduce the correct signals that guide the cells towards a
      desirable behaviour. Nanotechnology is not only an excellent tool to produce
      material structures that mimic the biological ones but also holds the promise of
      providing efficient delivery systems. The application of nanotechnology to
      regenerative medicine is a wide issue and this short review will only focus on
      aspects of nanotechnology relevant to biomaterials science. Specifically, the
      fabrication of materials, such as nanoparticles and scaffolds for tissue
      engineering, and the nanopatterning of surfaces aimed at eliciting specific
      biological responses from the host tissue will be addressed.

PMID- 18036686
TI  - Biogas as a resource-efficient vehicle fuel.
AB  - There are currently strong incentives for increased use of renewable fuels in the
      transport sector worldwide. However, some bioethanol and biodiesel production
      routes have limitations with regard to resource efficiency and reduction of
      greenhouse gases. More efficient biofuel systems are those based on
      lignocelluloses and novel conversion technologies. A complementary strategy to
      these is to increase the production of biogas from the digestion of organic
      residues and energy crops, or from byproducts of ethanol and biodiesel
      production. Compared with other biomass-based vehicle fuels available so far,
      biogas often has several advantages from an environmental and resource-efficiency
      perspective. This provides the motivation for further technological development
      aiming to reduce costs and thereby increased economic competitiveness of biogas
      as a vehicle fuel.

PMID- 18036687
TI  - Intensified irinotecan-based neoadjuvant chemoradiotherapy in rectal cancer: four
      consecutive designed studies to minimize acute toxicity and to optimize efficacy
      measured by pathologic complete response.
AB  - BACKGROUND: The objective of the present study was to analyse toxicity and
      efficacy of irinotecan-based neoadjuvant chemoradiotherapy by the help of four
      consecutively planed and prospectively performed phase II studies. PATIENTS AND
      METHODS: Patients with locally advanced rectal cancer received radiotherapy and
      concurrently chemotherapy consisting 5-Fu/capecitabine in a continuous or
      intermittent application and irinotecan in two different total doses (240 vs. 200
      mg/m(2)). RESULTS: Diarrhea CTC grade III was seen in 35% in continuous
      application of 5-Fu/capecitabine versus 12.5% in intermittent application (p=
      0,008). Complete response according to the irinotecan dose during
      chemoradiotherapy (240 mg/m(2) vs. 200 mg/m(2)) was 24% and 0%. CONCLUSIONS:
      Chemoradiotherapy of the last phase II study with intermittent capecitabine (1500
      mg/m(2)/day, delivered on days 1-14 and 22-35) and irinotecan (4 x 60 mg/m(2))
      concurrently to radiotherapy is a safe treatment with low toxicity and high
      efficacy.

PMID- 18036688
TI  - Differences in abdominal organ movement between supine and prone positions
      measured using four-dimensional computed tomography.
AB  - BACKGROUND AND PURPOSE: To analyze the differences in intrafractional organ
      movement throughout the breathing cycles between the supine and prone positions
      using four-dimensional computed tomography (4D CT). MATERIALS AND METHODS: We
      performed 4D CT on nine volunteers in the supine and prone positions, with each
      examinee asked to breathe normally during scanning. The movement of abdominal
      organs in the cranio-caudal (CC), anterior-posterior (AP) and right-left (RL)
      directions was quantified by contouring on each phase between inspiration and
      expiration. RESULTS: The mean intrafractional motions of the hepatic dome, lower
      tip, pancreatic head and tail, both kidneys, spleen, and celiac axis in the
      supine/prone position were 17.3/13.0, 14.4/11.0, 12.8/8.9, 13.0/10.0, 14.3/12.1,
      12.3/12.6, 11.7/12.6 and 2.2/1.8mm, respectively. Intrafractional movements of
      the liver dome and pancreatic head were reduced significantly in the prone
      position. The CC directional excursions were major determinants of the 3D
      displacements of the abdominal organs. Alteration from the supine to the prone
      position did not change the amount of intrafractional movements of kidneys,
      spleen, and celiac axis. CONCLUSION: There was a significant reduction in the
      movements of the liver and pancreas during the prone position, especially in the
      CC direction, suggesting possible advantage of radiotherapy to these organs in
      this position.

PMID- 18036689
TI  - Hypofractionated radiotherapy for the palliation of advanced head and neck cancer
      in patients unsuitable for curative treatment--"Hypo Trial".
AB  - BACKGROUND AND PURPOSE: The primary purpose of the trial was to assess rate of
      tumour response to a hypofractionated course of radiotherapy in patients with
      incurable squamous cell carcinoma of the head and neck (HNSCC). Secondary
      objectives included radiation toxicity, symptom control, quality of life (QoL)
      and progression-free and overall survival. PATIENTS AND METHODS: Patients were
      planned to receive 30 Gy in 5 fractions at 2/week, at least 3 days apart, with an
      additional boost of 6 Gy for small volume disease (< or =3 cm) in suitable
      patients. Thirty-seven patients were enrolled between August 2004 and March 2006.
      Median age was 68 (43-87) years, 81% were male and the predominant primary site
      was oropharynx (32%). The majority (73%) presented with Stage III-IV disease.
      RESULTS: Thirty-five patients received radiotherapy, 1 died prior to treatment
      and one refused treatment. Of the 35 patients receiving radiotherapy, 31 (88%)
      received > or =30 Gy. Of the 35 patients who received treatment the overall
      objective response was 80%. Grade 3 mucositis and dysphagia were experienced in
      9/35 (26%) and 4/35 (11%), respectively. QoL and symptom control were assessable
      in 21 patients. Thirteen (62%) reported an overall improvement in QoL and 14
      (67%) experienced an improvement in pain. The median time to progression and
      death was 3.9 and 6.1 months, respectively. CONCLUSION: The "Hypo Trial" regimen
      provided effective palliative treatment in HNSCC unsuitable for curative
      treatment. Compliance was excellent and resulted in high response rates, symptom
      control and improvement in QoL with acceptable toxicity. However, progression
      free and overall survival was short.

PMID- 18036690
TI  - Intensity-modulated radiation therapy in head and neck cancer: prescribed dose,
      clinical challenges and results.
AB  - PURPOSE: To analyse clinical and dosimetric characteristics with regard to
      clinical constraints in head and neck cancer patients treated with intensity
      modulated radiotherapy (IMRT). MATERIALS AND METHODS: Between August 2001 and
      July 2005, 75 patients with non-metastatic head and neck cancers were treated
      with IMRT with curative intent. Dose-volume histograms (DVH) drawn up from
      inverse dosimetry were analysed and compared to the prescription according to the
      clinical presentation of the disease. RESULTS: For bilateral irradiation, the
      mean doses delivered to the contralateral and ipsilateral parotid glands were,
      respectively, 28.1 and 26.3Gy. Dose constraints to the submandibular glands were
      only respected for the contralateral gland during unilateral irradiation. For
      tumors located in paranasal sinuses, the maximal dose to the contralateral and
      ipsilateral optic nerves remained significantly lower than the constraint doses
      while the constraints for the anterior part of the eyes could not be respected.
      CONCLUSIONS: Significant differences were observed concerning respect of the
      constraints applied to the parotid or to the submandibular glands for medial
      tumors. The respect of constraints for the organs at risk critically depends on
      the location and size of the primary tumor and on the definition of the CTV. The
      clinical impact has to be further evaluated.

PMID- 18036691
TI  - Outcome of early detection and radiotherapy for occult spinal cord compression.
AB  - Retrospective analysis in 150 patients with metastatic prostate cancer was
      conducted to determine whether early detection with MRI spine and treatment of
      clinically occult spinal cord compromise (SCC) facilitate preservation of
      neurologic function. Our results suggest that prophylactic radiotherapy for
      patients with back pain or radiological SCC without neurologic deficit may
      facilitate preservation of neurologic function. Thus MRI surveillance for SCC may
      be important for prostate cancer patients with bone metastases.

PMID- 18036692
TI  - P50 sensory gating and attentional performance.
AB  - Sensory gating refers to the preattentional filtering of irrelevant sensory
      stimuli. This process may be impaired in schizotypy, which is a trait also
      associated with cigarette smoking. This association may in part stem from the
      positive effects of smoking on sensory gating and attention. The relationship
      among sensory gating, smoking, schizotypy and attention was examined in 39
      undergraduates. Sensory gating was indexed by the P50 suppression paradigm, and
      attention was measured by the Attention Network Test (ANT) and a Stroop task.
      Results showed sensory gating to be positively correlated with performances on
      ANT and Stroop reflected in better alerting, less conflict between stimuli,
      faster reaction time, and greater accuracy. Smokers showed a pattern of a greater
      number of significant correlations between sensory gating and attention in
      comparison to non-smokers, although the relationship between sensory gating and
      attention was not affected by schizotypy. The majority of significant
      correlations were found in the region surrounding Cz. These findings are
      discussed relative to the potential modifying influence of smoking and schizotypy
      on sensory gating and attention.

PMID- 18036693
TI  - Magnetosensory evoked potentials: consistent nonlinear phenomena.
AB  - Electromagnetic fields (EMFs) having strengths typically found in the general
      environment can alter brain activity, but the reported effects have been
      inconsistent. We theorized that the problem arose from the use of linear methods
      for analyzing what were actually nonlinear phenomena, and therefore studied
      whether the nonlinear signal-processing technique known as recurrence
      quantification analysis (RQA) could be employed as the basis of a reliable method
      for demonstrating consistent changes in brain activity. Our primary purpose was
      to develop such a method for observing the occurrence of evoked potentials in
      individual subjects exposed to magnetic fields (2G, 30 and 60 Hz). After all
      conditions that affected the analysis of the EEG were specified in advance, we
      detected magnetosensory evoked potentials (MEPs) in all 15 subjects (P<0.05 in
      each experiment). The MEPs, which occurred within the predicted latency interval
      of 109-504 ms, were independent of the frequency and the direction of the field,
      and were not detected using the traditional linear method of analysis, time
      averaging. When the results obtained within subjects were averaged across
      subjects, the evoked potentials could not be detected, indicating how real
      nonlinear phenomena can be averaged away when the incorrect method of analysis is
      used. Recurrence quantification analysis, but not linear analysis, permitted
      consistent demonstration of MEPs. The use of nonlinear analysis might also
      resolve apparent inconsistencies in other kinds of brain studies.

PMID- 18036694
TI  - Correlation between the change in the kinetics of the ribosomal RNA rrnB P2
      promoter and the transition from lag to exponential phase with Pseudomonas
      fluorescens.
AB  - Developing accurate mathematical models to describe the pre-exponential lag phase
      in food-borne pathogens presents a considerable challenge to food
      microbiologists. While the growth rate is influenced by current environmental
      conditions, the lag phase is affected in addition by the history of the inoculum.
      A deeper understanding of physiological changes taking place during the lag phase
      would improve accuracy of models, and in earlier studies a strain of Pseudomonas
      fluorescens containing the Tn7-luxCDABE gene cassette regulated by the rRNA
      promoter rrnB P2 was used to measure the influence of starvation, growth
      temperature and sub-lethal heating on promoter expression and subsequent growth.
      The present study expands the models developed earlier to include a model which
      describes the change from exponential to linear increase in promoter expression
      with time when the exponential phase of growth commences. A two-phase linear
      model with Poisson weighting was used to estimate the lag (LPDLin) and the rate
      (RLin) for this linear increase in bioluminescence. The Spearman rank correlation
      coefficient (r=0.830) between the LPDLin and the growth lag phase (LPDOD) was
      extremely significant (P<or=0.001). A combined model was constructed which
      simulated the promoter activity over the whole range of cell adaptation and
      exponential growth. These results suggest that models based on measurable
      physiological changes in the cells can be useful in predicting the behaviour of
      food-borne pathogens.

PMID- 18036695
TI  - Phenotypic and genotypic identification of lactic acid bacteria isolated from
      ethnic fermented bamboo tender shoots of North East India.
AB  - Mesu, soidon, soibum and soijim are ethnic fermented bamboo tender shoot products
      prepared by the people in North East India. Microbiological analysis of mesu,
      soidon, soibum and soijim showed the population dominated by lactic acid bacteria
      (LAB) ranging up to 10(8) cfu g(-1). The phenotypic characterisation of
      predominant LAB isolated from the fermented bamboo shoot products was based on
      general morphology, physiological tests, API and Biolog systems. The genotypic
      characterisation of LAB was based on RAPD-PCR, rep PCR, species-specific PCR
      techniques, 16S rRNA gene sequencing and DNA-DNA hybridisation. Predominant
      functional LAB strains associated with the fermented bamboo shoot products were
      identified as Lactobacillus brevis, Lb. plantarum, Lb. curvatus, Pediococcus
      pentosaceus, Leuconostoc mesenteroides subsp. mesenteroides, Leuc. fallax, Leuc.
      lactis, Leuc. citreum and Enterococcus durans.

PMID- 18036696
TI  - HIV-1 p17 binds heparan sulfate proteoglycans to activated CD4(+) T cells.
AB  - We have previously shown that HIV-1 p17 binds to activated peripheral blood
      mononuclear cells and enhances secretion of pro-inflammatory cytokines, but we
      were unable to define a ligand on activated cells. In this work we evaluate the
      hypothesis that HIV-1 p17 may be a heparin/heparan sulfate-binding protein. HIV-1
      p17 contains C- and N-terminal sequences with positively charged residues and a
      consensus cluster for heparin binding. We demonstrated by affinity chromatography
      that HIV-1 p17 binds strongly to heparin-agarose at physiological pH. Soluble
      heparins and heparan sulfate but not chondroitin 4-sulfate and dextran sulfate
      inhibit binding of HIV-1 p17 to heparin solid phase and to activated CD4(+) T
      cells. Furthermore the inhibition of cell sulfatation by chlorate treatment
      completely counteracts HIV-1 p17 binding to activated cells. These results
      indicate for the first time that HIV-1 p17 can be ascribed to the heparin binding
      protein family and suggest that this interaction might play a key role in the
      ability of the protein to induce an inflammatory effect on activated cells.

PMID- 18036697
TI  - Appearance of intratypic recombination of enterovirus 71 in Taiwan from 2002 to
      2005.
AB  - Genetic recombination is a well-known phenomenon for enteroviruses. In this
      study, we determined the phylogenetic relationships of five distinct regions of
      the EV71 genome for 73 EV71 isolates from 1986 and from 1998 to 2005 in Taiwan.
      Phylogenetic analyses showed that the 5'-UTR, VP4-VP2, VP1, and 3D regions of
      EV71 isolated in 2004 and 2005 were grouped into genotype C. However, the 2B
      region of these isolates differed in that it grouped with genotype B, indicating
      recombination within EV71 had occurred. This intratypic recombination was first
      seen in 2002 and became predominant in 2004 and 2005. The simplot and bootscan
      analyses identified two recombination points located at the 3'-termini of the 2A
      and 3C regions. This intratypic recombination was identified among naturally
      circulating EV71 isolates in Taiwan, therefore, it suggests that nonstructural
      genes may recombine to produce new EV71 variants.

PMID- 18036699
TI  - Influence of smoking on histologic type and the efficacy of adjuvant chemotherapy
      in resected non-small cell lung cancer.
AB  - BACKGROUND: Numerous studies indicate that smoking is associated with many
      factors that contribute to poorer outcomes in patients with lung cancer and may
      limit the efficacy of treatment, especially in advanced non-small cell lung
      cancer (NSCLC), but little is known about its effect on treatment of resected
      NSCLC. The aim of this study was to determine the impact of smoking on adjuvant
      chemotherapy in patients with NSCLC. Another objective of our study was to
      investigate the relationship between smoking status and the clinical
      characteristics of patients with NSCLC. METHODS: A sretrospective analysis was
      carried out on patients with NSCLC seen during the period January 1990 until
      December 2000. Clinical characteristics and survival outcomes were reviewed and
      compared between patients with different smoking status. RESULTS: Of 1270
      patients who were eligible for analysis, 319 received adjuvant chemotherapy. Sex,
      age, tumor location, tumor size, symptoms including hemoptysis, cough, blood in
      sputum and histologic types were different between smokers and non-smokers.
      Patients with PY>22.75 were more likely to have squamous cell lung cancer. In non
      smokers and patients with PY< or =10, 5-year survival was better for patients
      receiving adjuvant chemotherapy compared to those without adjuvant chemotherapy,
      but in patients with PY>10, adjuvant chemotherapy did not have a survival
      benefit. CONCLUSIONS: A patient with PY>22.75 is more likely to develop squamous
      cell lung cancer. In non-smokers and patients with PY< or=10, adjuvant
      chemotherapy has a survival benefit.

PMID- 18036698
TI  - Adenovirus vector induced innate immune responses: impact upon efficacy and
      toxicity in gene therapy and vaccine applications.
AB  - Extensively characterized, modified, and employed for a variety of purposes,
      adenovirus (Ad) vectors are generally regarded as having great potential by many
      applied virologists who wish to manipulate and use viral biology to achieve
      beneficial clinical outcomes. Despite widespread functional prominence and
      utility (i.e., Ad-based clinical trials have begun to progress to critical Phase
      III levels, it has recently become apparent that investigations regarding the
      innate immune response to Ads may reveal not only reasons behind previous
      failures, but also reveal novel insights that will allow for safer, more
      efficacious uses of this important gene transfer platform. Insights gained by the
      exploration of Ad induced innate immune responses will likely be most important
      to the fields of vaccine development, since Ad-based vaccines are regarded as one
      of the more promising vaccine platforms in development today. Adenovirus is
      currently known to interact with several different extracellular, intracellular,
      and membrane-bound innate immune sensing systems. Past and recent studies
      involving manipulation of the Ad infectious cycle as well as use of different
      mutants have shed light on some of the initiation mechanisms underlying Ad
      induced immune responses. More recent studies using microarray-based analyses,
      genetically modified cell lines and/or mouse mutants, and advanced generation Ad
      vectors have revealed important new insights into the scope and mechanism of this
      cellular defensive response. This review is an attempt to synthesize these
      studies, update Ad biologists to the current knowledge surrounding these
      increasingly important issues, as well as highlight areas where future research
      should be directed. It should also serve as a sobering reality to researchers
      exploring the use of any gene transfer vector, as to the complexities potentially
      involved when contemplating use of such vectors for human applications.

PMID- 18036700
TI  - ERCC1 expression by immunohistochemistry and EGFR mutations in resected non-small
      cell lung cancer.
AB  - Expression of excision repair cross-complementation group 1 (ERCC1) is important
      for resistance to platinum agents. Mutations of epidermal growth factor receptor
      (EGFR) are related to the responsiveness to tyrosine kinase inhibitors in non
      small cell lung cancer (NSCLC). This study was performed to determine if ERCC1
      expression and EGFR are related to the prognosis of resected NSCLC, and to
      determine if ERCC1 expression and EGFR mutations are related. We used
      immunohistochemistry (IHC) to evaluate ERCC1 expression in tumors from 130
      patients with curatively resected NSCLC. The median H-score was used as a cut-off
      for ERCC1 IHC. EGFR mutations were analyzed in exons 18, 19 and 21. ERCC1
      expression was detected in tumors from 80 patients (61.5%). ERCC1 was expressed
      more frequently in smokers and in squamous cell carcinomas. Patients with a
      positive ERCC1 expression survived longer than ERCC1-negative patients (median
      overall survival 7.6 years for ERCC1-positive vs. 4.0 years for ERCC1-negative,
      P=0.046). Subsequent multivariate analysis suggested that ERCC1 expression is an
      independent prognostic marker of longer survival (hazard ratio: 0.598, 95%
      confidence interval: 0.357-1.001). EGFR mutations were found in 25 patients
      (19.2%) but did not affect overall survival. Interestingly, EGFR mutations were
      more frequent in ERCC1-negative tumors (12.5% in ERCC1-positive vs. 30% in ERCC1
      negative tumors, P=0.014). In conclusion, ERCC1 expression was identified as a
      positive prognostic marker in resected NSCLC. In addition, EGFR mutations were
      more frequently found in ERCC1-negative tumors.

PMID- 18036701
TI  - Topotecan and cisplatin in combination with concurrent twice-daily chemoradiation
      in limited disease small cell lung cancer-a Danish Oncological Lung Cancer Group
      (DOLG) phase II trial.
AB  - INTRODUCTION: The longest survival time reported in randomised trials of limited
      disease (LD) SCLC has been achieved with early twice-daily concurrent
      chemoradiation. Topotecan is active in recurrent SCLC and in extensive disease as
      first line treatment. AIM: To incorporate and assess the effect of topotecan with
      concurrent twice-daily radiochemotherapy in LD SCLC. PATIENT AND METHODS:
      Multicentre phase II study of three cycles of regimen A (topotecan i.v.,
      1.5mg/m(2), day 1-5; cisplatin 50mg/m(2), day 1) and three cycles of regimen B
      (etoposide i.v., 120mg/m(2), day 1-3; carboplatin, AUC=5, day 1; vincristine,
      1.3mg/m(2), day 1) given in the following sequence: A-B-B-A-B-A every 21 days.
      Twice-daily radiotherapy (1.5Gyx30, 10fr/wk, 45Gy) was delivered concurrently
      with the first cycle B. Prophylactic cranial irradiation was offered to patients
      (pts) in complete remission. Eligible were pts with LD SCLC with no prior
      treatment for SCLC, adequate organ functions, and WHO performance status (PS) <
      or =2. Pts older than 64 years with PS=2 and LDH>two times the upper limit were
      excluded. RESULT: Fourty-five pts were included in four centres. Five patients
      did not meet the inclusion criteria. The median age of the eligible pts was 60
      years, range 43-75. PS was < or =1 in 90% of pts. Non-haematological toxicity was
      mild except grade 3 esophagitis, which was observed in 26.5% of pts. One pt
      developed an esophageal stricture. Grade 3/4 leucopenia and thrombocytopenia were
      observed in 82.5% and 75.0 of pts, respectively. One patient died due to
      neutropenic sepsis. The overall response rate was 77.5% with 30.0% achieving a
      complete response. Median progression-free survival was 11.8 months (95% CI: 1.3
      22.2). Median overall survival was 22.9 months (95% CI: 13.4-31.5) and 5-year
      survival was 21%. CONCLUSION: The combination of topotecan and cisplatin with
      concurrent twice-daily chemoradiation results in long-term survivors. As expected
      the incidence of severe esophagitis is high.

PMID- 18036703
TI  - Therapeutic hypothermia in cocaine-induced cardiac arrest.
AB  - Therapeutic hypothermia is an exciting new treatment modality that has been shown
      to have significantly improved outcomes in comatose survivors of cardiac arrest.
      One of the exclusion criteria of the landmark studies on therapeutic hypothermia
      was a potential toxin-induced cause of the persistent comatose state and
      presumably of the cardiac arrest itself. We present the first reported case of a
      comatose survivor of cocaine-induced cardiac arrest successfully treated with
      therapeutic hypothermia.

PMID- 18036702
TI  - Predicting intentions to purchase organic food: the role of affective and moral
      attitudes in the Theory of Planned Behaviour.
AB  - This study examined the usefulness of integrating measures of affective and moral
      attitudes into the Theory of Planned Behaviour (TPB)-model in predicting purchase
      intentions of organic foods. Moral attitude was operationalised as positive self
      rewarding feelings of doing the right thing. Questionnaire data were gathered in
      three countries: Italy (N=202), Finland (N=270) and UK (N=200) in March 2004.
      Questions focussed on intentions to purchase organic apples and organic ready-to
      cook pizza instead of their conventional alternatives. Data were analysed using
      Structural Equation Modelling by simultaneous multi-group analysis of the three
      countries. Along with attitudes, moral attitude and subjective norms explained
      considerable shares of variances in intentions. The relative influences of these
      variables varied between the countries, such that in the UK and Italy moral
      attitude rather than subjective norms had stronger explanatory power. In Finland
      it was other way around. Inclusion of moral attitude improved the model fit and
      predictive ability of the model, although only marginally in Finland. Thus the
      results partially support the usefulness of incorporating moral measures as well
      as affective items for attitude into the framework of TPB.

PMID- 18036704
TI  - Fluctuations of hippocampal neuronal protein levels over the estrous cycle in the
      rat.
AB  - Hippocampal function is known to be estrous-cycle-dependent but information on
      estrous-cycle-dependent protein expression is limited. It was therefore the aim
      to study protein levels of the neuronal network over the estrous cycle in the
      hippocampus of female rats and in males showing protein chemical neuroanatomy in
      this area. Female and male OFA Sprague-Dawley rats were used and females were
      grouped to proestrous, estrous, metestrous and diestrous by using vaginal smears.
      Hippocampal tissue was taken, proteins extracted, run on two-dimensional gel
      electrophoresis and proteins were identified by mass spectrometry methods (MALDI
      TOF-TOF and nano-LC-ESI-MS/MS). Spot volumes were quantified with specific
      software. A Synapsin-1 expression form was differentially regulated between
      proestrous and diestrous, a Synapsin IIa expression form was differentially
      regulated between proestrous and metestrous, the sum of ERC-2 proteins organizing
      the cytomatrix at the nerve terminals active zone was showing sex-dependent
      levels in the proestrous phase and Neurofilament triplet L protein was
      differentially expressed between the estrous phase and males. The findings may
      represent estrous-cycle-dependent hippocampal synaptic function that has been
      shown already in terms of electrophysiology and neuroanatomy. Neurofilament
      changes over the estrous cycle may reflect endoskeleton changes over the estrous
      cycle. We learn from this study, although increasing complexity of protein
      knowledge, that the estrous cycle and not only the sex per se has to be taken
      into account for design of future studies and interpretation of previous work at
      the protein level.

PMID- 18036706
TI  - [Efficacy of imatinib in FIP1L1-PDGFRA positive hypereosinophilic syndrome].
AB  - Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders
      characterized by marked peripheral blood and tissue eosinophilia resulting in
      organ damage. Recent advances in molecular biology have led to the identification
      of a FIP1L1-PDGFRA fusion gene as a recurrent abnormality in some patients with
      HES. This fusion gene results from a cryptic 4q12 interstitial deletion involving
      an 800 kb region. Recent reports indicate that this subtype of HES is imatinib
      responsive with rapid and complete haematological remissions. Here we report two
      patients successfully treated with imatinib.

PMID- 18036707
TI  - Relationships of blood lead to calcium, iron, and vitamin C intakes in Brazilian
      pregnant women.
AB  - BACKGROUND & AIMS: This study aimed to determine the relationship between blood
      lead concentrations and calcium, iron and vitamin C dietary intakes of pregnant
      women. METHODS: Included in the study were 55 women admitted to a hospital, for
      delivery, from June to August 2002. A food frequency questionnaire was applied to
      determine calcium, iron and vitamin C intakes, and a general questionnaire to
      obtain data on demographic-socioeconomic condition, obstetric history, smoking
      habit, and alcohol intake. Blood lead and haemoglobin were determined,
      respectively, by atomic absorption spectrometry and by the haemoglobinometer
      HemoCue. Multiple linear regression models were used to determine the
      relationship between blood lead and calcium, iron and vitamin C intakes, and
      haemoglobin levels, controlling for confounders. RESULTS: The final model of the
      regression analysis detected an inverse relationship between blood lead and age
      of the women (p=0.011), haemoglobin (p=0.001), vitamin C (p=0.012), and calcium
      intake (p<0.001) (R(2)=0.952). One hundred percent, 98.2% and 43.6% of the women
      were below the adequate intake (AI) for calcium, and below the recommended
      dietary allowances (RDA) for iron, and vitamin C, respectively. CONCLUSION:
      Despite the small sample size, the results of this study suggest that maternal
      age, haemoglobin, vitamin C intake, and calcium intake may interfere with blood
      concentrations of lead.

PMID- 18036709
TI  - Prevention and control of viral hepatitis through adolescent health programmes in
      Europe.
AB  - The Viral Hepatitis Prevention Board jointly organized with the European Union
      for School and University Health and Medicine a meeting on the prevention and
      control of viral hepatitis through adolescent health programmes in Europe, held
      in Ljubljana, Slovenia, 15-16 March 2007. Participants from some 16 countries in
      Europe as well as the United States of America emphasized the importance of
      reaching adolescents mainly through school health programmes, provided an
      overview of currently existing youth health systems and reviewed their
      experiences with childhood and adolescent immunization programmes. The meeting
      concluded with a discussion of issues, lessons learnt, opportunities and action
      points for the future.

PMID- 18036708
TI  - Clinical and immunologic responses to multiple doses of IMVAMUNE (Modified
      Vaccinia Ankara) followed by Dryvax challenge.
AB  - Smallpox vaccination with replication deficient vaccinia strains such as Modified
      Vaccinia Ankara (MVA) may induce protective immunity with improved safety and
      tolerability profiles compared with currently available smallpox vaccines. Ninety
      subjects were randomized equally to six groups in a partially blinded,
      randomized, controlled clinical trial. IMVAMUNE (MVA-BN, Bavarian Nordic A/S,
      Kvistgard, Denmark) vaccine or placebo was administered at Study Days 0 and 28 by
      subcutaneous or intramuscular injection and five groups were challenged with
      Dryvax at study Day 112. Vaccination with two doses of IMVAMUNE was safe and well
      tolerated compared to Dryvax. IMVAMUNE produced comparable cellular and humoral
      immune responses to one dose of Dryvax and the immunity induced appears robust 90
      days post-vaccination by evidence of attenuated primary cutaneous reaction
      responses following Dryvax. IMVAMUNE vaccination prior to Dryvax reduced virus
      replication at the Dryvax site, decreased the size of the primary cutaneous
      lesion, and decreased the time to healing but did not completely ameliorate the
      immune response.

PMID- 18036710
TI  - Genotypic variation of nitrogen use efficiency in Indian mustard.
AB  - This experiment was conducted to investigate the variation of nitrogen efficiency
      (NE), nitrogen uptake efficiency (UE), physiological nitrogen use efficiency
      (PUE) among Indian mustard genotypes, grown under N-insufficient and N-sufficient
      conditions. Nitrogen efficiency varied from 52.7 to 92.8. Seed yield varied from
      1.14 t ha(-1) to 3.21 t ha(-1) under N-insufficient condition, while 2.14 t ha(
      1)-3.33 t ha(-1) under N-sufficient condition. Physiological basis of this
      difference was explained in terms of nitrogen uptake efficiency and physiological
      nitrogen use efficiency, and their relationship with the growth and yield
      characteristics. While nitrogen uptake efficiency was positively correlated with
      plant biomass (0.793**), leaf area index (0.664*), and leaf nitrogen content
      (0.783**), physiological nitrogen use efficiency is positively correlated with
      photosynthetic rate (0.689**) and yield (0.814**). This study suggests that
      genotype having high nitrogen uptake efficiency and high physiological nitrogen
      use efficiency might help in reducing the nitrogen load on soil without any
      penalty on the yield.

PMID- 18036711
TI  - Attention-deficit/hyperactivity disorder and social dysfunctioning.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is associated with functional
      impairments in different areas of daily life. One such area is social
      functioning. The purpose of this paper is to critically review research on social
      dysfunctioning in children with ADHD. Children with ADHD often have conflicts
      with adults and peers, and suffer from unpopularity, rejection by peers, and a
      lack of friendships, in part as a consequence of their ADHD symptoms. Comorbid
      oppositional defiant or conduct disorder aggravates these impairments. In some
      cases the inadequate social behavior of children with ADHD may be
      phenomenologically and etiologically related to pervasive developmental disorders
      (PDD). However, the causes and consequences of PDD symptoms in ADHD are
      understudied. Also, the relative contributions of ADHD, on the one hand, and
      comorbid disorders, on the other, to the course of social impairments are
      unknown. Social dysfunctioning in children with ADHD appears to increase their
      risk of later psychopathology other than ADHD. Thus far effective treatment for
      social dysfunctioning is lacking. Future research should address the exact nature
      and long-term consequences of social dysfunctioning in children with ADHD, and
      focus on development of effective treatment strategies.

PMID- 18036712
TI  - The weight of place: a multilevel analysis of gender, neighborhood material
      deprivation, and body mass index among Canadian adults.
AB  - This study examined the impact of neighborhood material deprivation on gender
      differences in body mass index (BMI) for urban Canadians. Data from a national
      health survey of adults (Canadian Community Health Survey Cycles 1.1/2.1) were
      combined with census tract-level neighborhood data from the 2001 census. Using
      multilevel analysis we found that living in neighborhoods with higher material
      deprivation was associated with higher BMI. Compared to women living in the most
      affluent neighborhoods, women living in the most deprived neighborhoods had a BMI
      score 1.8 points higher. For women 1.65 m in height (5'4'' inches), this
      translated into a 4.8 kg or 11 lb difference. For men, living in affluent
      neighborhoods was associated with higher BMI (7 lb) relative to men living in
      deprived neighborhoods. The relative disadvantage for men living in pockets of
      affluence and women living in pockets of poverty persisted after adjusting for
      age, married and visible minority status, educational level, self-perceived
      stress, sense of belonging, and lifestyle factors, including smoking, exercise,
      diet, and chronic health conditions. The implication of these disparate findings
      for men and women is that interventions that lead to healthy weight control may
      need to be gender responsive. Our findings also suggest that what we
      traditionally have thought to be triggering factors for weight gain and
      maintenance of unhealthy BMI-lifestyle and behavioral factors-are not sufficient
      explanations. Indeed, these factors account for only a portion of the explanation
      of why neighborhood stress is associated with BMI. Cultural attitudes about the
      body that pressure women to meet the thin ideal which can lead to an unhealthy
      cycle of dieting and, subsequent weight gain, and the general acceptability of
      the heavier male need to be challenged. Education and intervention within a
      public health framework remain important targets for producing healthy weight.

PMID- 18036714
TI  - Fragrance material review on isobutyl cinnamate.
AB  - A toxicologic and dermatologic review of isobutyl cinnamate when used as a
      fragrance ingredient is presented.

PMID- 18036715
TI  - Fragrance material review on isopropyl cinnamate.
AB  - A toxicologic and dermatologic review of isopropyl cinnamate when used as a
      fragrance ingredient is presented.

PMID- 18036716
TI  - Fragrance material review on alpha-methylcinnamic alcohol.
AB  - A toxicologic and dermatologic review of alpha-methylcinnamic alcohol when used
      as a fragrance ingredient is presented.

PMID- 18036717
TI  - Do ATP and NO interact in the CNS?
AB  - Enzymatically derived NO and extracellular ATP are receiving greater attention
      due to their role as messengers in the CNS during different physiological and
      pathological processes. Ionotropic (P2XR) and metabotropic (P2YR) purinergic
      receptors mediate ATP effects and are present throughout the body. Particularly
      P2XR are crucial for brain plasticity mechanisms, and are involved in the
      pathogenesis of different CNS illnesses. NO does not have a specific receptor and
      its actions are directly dependent on the production on demand by different
      nitric oxide synthase isoforms. NO synthesizing enzymes are present virtually in
      all tissues, and NO influences multifarious physiological and pathological
      functions. Interestingly, various are the tissue and organs modulated by both ATP
      and NO, such as the immune, brain and vascular systems. Moreover, direct
      interactions between purinergic and nitrergic mechanisms outside the CNS are well
      documented, with several studies also indicating that ATP and NO do participate
      to the same CNS functions. In the past few years, further experimental evidence
      supported the physiological and pathological relevance of ATP and NO direct
      interactions in the CNS. The aim of the present review is to provide an account
      of the available information on the interplay between purinergic and nitrergic
      systems, focussing on the CNS. The already established relevance of ATP and NO in
      different pathological processes would predict that the knowledge of ATP/NO cross
      talk mechanisms would support pharmacological approaches toward the development
      of novel ATP/NO combined pharmacological agents.

PMID- 18036718
TI  - Detailed molecular characterization of cord blood-derived endothelial
      progenitors.
AB  - OBJECTIVE: Given their involvement in pathological and physiological
      angiogenesis, there has been growing interest in understanding and manipulating
      endothelial progenitor cells (EPC) for therapeutic purposes. However, detailed
      molecular analysis of EPC before and during endothelial differentiation is
      lacking and is the subject of the present study. MATERIALS AND METHODS: We report
      a detailed microarray gene-expression profile of freshly isolated (day 0) human
      cord blood (CB)-derived EPC (CD133+KDR+ or CD34+KDR+), and at different time
      points during in vitro differentiation (early: day 13; late: day 27). RESULTS:
      Data obtained reflect an EPC transcriptome enriched in genes related to
      stem/progenitor cells properties (chromatin remodeling, self-renewal, signaling,
      cytoskeleton organization and biogenesis, recruitment, and adhesion). Using a
      complementary DNA microarray enriched in intronic transcribed sequences, we
      observed, as well, that naturally transcribed intronic noncoding RNAs were
      specifically expressed at the EPC stage. CONCLUSION: Taken together, we have
      defined the global gene-expression profile of CB-derived EPC during the process
      of endothelial differentiation, which can be used to identify genes involved in
      different vascular pathologies.

PMID- 18036719
TI  - The relationship between prostate inflammation and lower urinary tract symptoms:
      examination of baseline data from the REDUCE trial.
AB  - OBJECTIVE: The ongoing REDUCE trial is a 4-yr, phase 3, placebo-controlled study
      to determine if daily dutasteride 0.5mg reduces the risk of biopsy detectable
      prostate cancer. Prostate biopsies performed in all men prior to entry were
      centrally reviewed, thus allowing an examination of the relationship between
      inflammatory changes and lower urinary tract symptoms (LUTS). METHODS: Eligible
      men were aged 50-75 yr, with serum prostate-specific antigen >or=2.5 ng/ml and
      <or=10 ng/ml (50-60 yr), or >or=3.0 ng/ml and <or=10 ng/ml (>60 yr) and an
      International Prostate Symptom Score (IPSS)<25 (or <20 if already on alpha
      blocker therapy). Acute prostatitis was an exclusion criterion. For a given
      individual, inflammation was assessed across all cores and the amount of
      inflammation scored as none (0), mild (1), moderate (2), or marked (3). LUTS was
      assessed with the use of the IPSS. The relationship between inflammation scores
      (averaged over all cores) and total IPSS; grouped IPSS (0-3, 4-7, 8-11, 12-15, 16
      19, >/=20); and irritative, obstructive, and nocturia subscores was determined by
      Spearman rank correlations. The relative contribution of inflammation, age, and
      body mass index was then examined with the use of linear regression analyses.
      RESULTS: Data were available for 8224 men. Statistically significant but
      relatively weak correlations were found between average and maximum chronic
      inflammation and IPSS variables (correlation coefficients, 0.057 and 0.036,
      respectively; p < 0.001 for total IPSS). Both age and average chronic
      inflammation were significant in the linear regression after adjustment for other
      covariates; for both variables, more severe inflammation was associated with
      higher IPSS scores. CONCLUSIONS: In the REDUCE population, there is evidence of a
      relationship between the degree of LUTS and the degree of chronic inflammation.
      Study entry criteria that selected older men and decreased enrolment of men with
      a greater degree of inflammation and LUTS may have limited the strength of this
      relationship. The impact of baseline prostate inflammation on progression of LUTS
      and/or associated complications will be determined during 4-yr longitudinal
      follow-up.

PMID- 18036720
TI  - Editorial comment on: the relationship between prostate inflammation and lower
      urinary tract symptoms: examination of baseline data from the REDUCE trial.

PMID- 18036721
TI  - Editorial comment on: daily treatment with sildenafil reverses endothelial
      dysfunction and oxidative stress in an animal model of insulin resistance.

PMID- 18036722
TI  - Editorial comment on: Urinary incontinence at orgasm: relation to detrusor
      overactivity and treatment efficacy.

PMID- 18036723
TI  - Re: Guido Barbagli. History and evolution of transpubic urethroplasty: a lesson
      for young urologists in training. Eur urol 2007;52:1290-2.

PMID- 18036724
TI  - The contribution of the levator ani nerve and the pudendal nerve to the
      innervation of the levator ani muscles; a study in human fetuses.
AB  - OBJECTIVES: The contributions of the pudendal and levator ani nerves to the
      innervation of the levator ani muscle (LAM) are disputed. Because of the
      relatively large size of the nerves in early life, we investigated this issue in
      human fetuses. METHODS: (Immuno)histochemically stained serial sections of nine
      human fetuses (9-22 wk of gestation) were investigated. Both the left and right
      sides of the fetal pelves were studied individually and 3D reconstructions were
      prepared. RESULTS: The levator ani nerve innervated the LAM in every pelvis,
      whereas a contribution of the pudendal nerve to the innervation of the LAM could
      be demonstrated in only 10 pelvic halves (56%). In 10 halves, we observed a
      communicating nerve branch between the pudendal and levator ani nerves that
      pierced the pelvic floor between the LAM and the coccygeus muscle. No sex
      differences were observed, but the innervation pattern did differ between the
      left and right side of a pelvis. CONCLUSIONS: The LAM often has a dual somatic
      innervation with the levator ani nerve as its constant and main neuronal supply.

PMID- 18036725
TI  - Editorial comment on: Urinary incontinence at orgasm: relation to detrusor
      overactivity and treatment efficacy.

PMID- 18036727
TI  - Daily treatment with sildenafil reverses endothelial dysfunction and oxidative
      stress in an animal model of insulin resistance.
AB  - OBJECTIVES: Patients with insulin resistance exhibit endothelial dysfunction with
      decreased nitric oxide (NO) production and increased oxidative stress. We
      postulated that daily sildenafil improved endothelial function in fructose-fed
      rats. METHODS AND RESULTS: Wistar rats were fed a standard or fructose-enriched
      diet (FFR) for 9 wk. From weeks 6-8, sildenafil was administered twice daily (sc,
      20 m g/kg), followed by a 1-wk washout. Concentration-response curves (CRCs) to
      endothelium-dependent (acetylcholine [Ach] and A23187) and -independent (sodium
      nitroprusside [SNP]) relaxing agents were performed on isolated precontracted
      aortas and superior mesenteric arteries (SMAs). Vascular cyclic guanosine
      monophosphate (cGMP) content, urinary excretion of nitrates/nitrites (NOx) and 8
      isoprostanes (IPT), and plasma levels of interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha) were evaluated. Relaxations to ACh were significantly
      reduced in aortas and SMAs of FFR. Sildenafil restored ACh-induced relaxations in
      aortas and provoked a significant leftward shift of the CRC to ACh in SMAs,
      whereas it did not modify the enhanced relaxations to SNP in FFR. IL-6, TNF
      alpha, vascular cGMP, and urinary NOx levels were not modified by the fructose or
      sildenafil treatment. Urinary IPT levels were significantly elevated in FFR and
      normalized by sildenafil. CONCLUSIONS: Endothelial dysfunction and oxidative
      stress associated with insulin resistance can be reversed by daily sildenafil,
      even 1 wk after treatment cessation.

PMID- 18036728
TI  - Urinary incontinence at orgasm: relation to detrusor overactivity and treatment
      efficacy.
AB  - OBJECTIVE: To understand the pathophysiological mechanism of incontinence during
      orgasm and to compare women affected by symptomatic detrusor overactivity (DO)
      with and without incontinence at orgasm in terms of efficacy of antimuscarinic
      treatment. METHODS: All consecutive sexually active women with incontinence
      during intercourse were prospectively included and divided into two groups: women
      with coital incontinence at orgasm or at penetration. The two forms of coital
      incontinence were correlated to the urodynamic finding of DO. Women complaining
      of overactive bladder (OAB) symptoms, with urinary incontinence at orgasm and
      urodynamically proven DO (cases), were prescribed tolterodine 4 mg extended
      release for at least 12 wk. The cases were compared in terms of efficacy of
      treatment on OAB symptoms to consecutive patients with symptomatic DO without
      coital incontinence (control group). RESULTS: Among the 1133 women who underwent
      urodynamic testings during the study period, 132 patients were eligible for final
      analysis. A significant difference in DO was observed in women with incontinence
      at orgasm (34 of 49; 69.4%) compared with women with incontinence during
      penetration (24 of 83; 28.9%) (p<0.0001). The 34 women with incontinence at
      orgasm associated with DO were given antimuscarinics treatment and were compared
      with 53 controls. Fourteen of 34 (41.2%) and 9 of 53 (17%) women did not respond
      to antimuscarinics in the cases and in the control group, respectively (p=0.023).
      CONCLUSIONS: Incontinence at orgasm is associated with DO in the majority of
      cases. This is the first study showing an inferior efficacy of antimuscarinic
      treatment in women with DO complaining of incontinence at orgasm.

PMID- 18036729
TI  - The inside-out trans-obturator sling: a novel surgical technique for the
      treatment of male urinary incontinence.
AB  - OBJECTIVES: To describe a new sling procedure for treating stress urinary
      incontinence (SUI) after radical prostatectomy (RP) and prospectively evaluate
      its short-term safety and efficacy. METHODS: The sling technique uses specific
      instruments and a polypropylene mesh with two arms that are passed inside to
      outside through the obturator foramens, pulled for compressing the bulbar urethra
      upward, and tied to each other across the midline. Patients with detrusor
      overactivity were excluded. Baseline and follow-up evaluations included
      uroflowmetry and continence and quality of life (QoL) questionnaires. Cure was
      defined by no pad use and improvement by a number of pads/d <or=2 and reduced by
      at least 50%. Complications were recorded. RESULTS: From April 2006 through
      February 2007, 20 consecutive patients suffering from post-RP SUI underwent the
      sling procedure using the same operative protocol. Preoperatively, 3 (15%), 11
      (55%), and 6 (25%) patients were using 2, 3-5, and >5pads/d, respectively. The
      procedure was preceded by an endoscopic urethrotomy in four patients. No
      perioperative complication was noted; three patients required suprapubic
      catheterization. At 6 mo, nine (45%) patients were cured and eight others (40%)
      were improved (1pad/d). QoL was significantly enhanced and 80% of patients were
      moderately to completely satisfied with the procedure. Preoperative and
      postoperative maximum flow rate and postvoid residual values were not
      statistically different. No sling infection, urethra erosion, persistent pain, or
      neurologic complications were observed. CONCLUSIONS: The inside-out trans
      obturator sling procedure appears to be safe and efficient at short term. Further
      studies are warranted to determine long-term outcome.

PMID- 18036730
TI  - Nephron-sparing surgery versus radical nephrectomy in the treatment of
      intracapsular renal cell carcinoma up to 7cm.
AB  - OBJECTIVE: To compare the oncologic outcomes of nephron-sparing surgery versus
      radical nephrectomy in intracapsular renal cell carcinoma (RCC) up to 7 cm by
      reviewing surgical experience retrospectively. METHODS: Data from 1290
      consecutive patients who had surgery for RCC have been stored in a dedicated
      database since 1983. We selected and reviewed those related to disease-free
      patients who had been treated for unilateral pT1a/pT1b pN0/Nx M0 carcinomas up to
      7 cm and later followed for a minimum of 12 mo. RESULTS: A total of 642 patients
      with mean follow-up of 72.9 mo were selected; 313 had been treated for tumours <4
      cm in diameter (176 nephron-sparing surgery, 137 nephrectomy), whereas 329 had
      been treated for tumours measuring > or =4 cm (52 nephron-sparing surgery, 277
      nephrectomy). The comparison between tumours <4 cm or > or =4 cm in diameter
      showed worse progression and disease-free survival rates for the latter, but the
      type of surgery (nephron-sparing or radical) seemed to have no significant
      impact. CONCLUSIONS: Conservative management can be cautiously suggested for RCC
      up to 7 cm because the worsening of prognosis as diameter increases shows no
      statistical differences for either nephron-sparing or radical surgery. The
      agreement of our results with those of similar studies available in the
      literature may suggest designing a prospective study to compare conservative and
      more radical surgery in the management of RCC up to 7 cm.

PMID- 18036731
TI  - Re: Guido Barbagli. History and evolution of transpubic urethroplasty: a lesson
      for young urologist in training. Eur urol 2007;52:1290-2.

PMID- 18036732
TI  - Editorial comment on: the contribution of the levator ani nerve and the pudendal
      nerve to the innervation of the levator ani muscles: a study in human fetuses.

PMID- 18036733
TI  - Role of the Nrf2-antioxidant system in cytotoxicity mediated by anticancer
      cisplatin: implication to cancer cell resistance.
AB  - The treatment of alkylating cytotoxic drug cisplatin is often limited by high
      incidence rate of resistance. In the present study, the potential involvement of
      the transcription factor Nrf2 in determination of cisplatin cytotoxicity has been
      investigated. Nrf2-deficient murine embryonic fibroblasts showed increased cell
      death, cytotoxicity, and apoptosis in response to cisplatin treatment compared to
      wild-type cells. Cisplatin-resistant human ovarian cancer SK-OV cells, which are
      retaining 25-fold higher levels of GSH than murine fibroblasts, could be
      sensitized by inhibition of Nrf2. Transfection with Nrf2 siRNA into SK-OV cells
      resulted in severe degree of GSH depletion and exacerbated cytotoxicity following
      cisplatin treatment compared to scrambled RNA control. In conclusion, we propose
      that the Nrf2 pathway, which plays a protective role in normal cells, can be a
      potential target to control cancer cell resistance to oxidants, cytotoxic
      chemicals, and radiation.

PMID- 18036734
TI  - The CSB Incident Screening Database: description, summary statistics and uses.
AB  - This paper briefly describes the Chemical Incident Screening Database currently
      used by the CSB to identify and evaluate chemical incidents for possible
      investigations, and summarizes descriptive statistics from this database that can
      potentially help to estimate the number, character, and consequences of chemical
      incidents in the US. The report compares some of the information in the CSB
      database to roughly similar information available from databases operated by EPA
      and the Agency for Toxic Substances and Disease Registry (ATSDR), and explores
      the possible implications of these comparisons with regard to the dimension of
      the chemical incident problem. Finally, the report explores in a preliminary way
      whether a system modeled after the existing CSB screening database could be
      developed to serve as a national surveillance tool for chemical incidents.

PMID- 18036735
TI  - Soil washing for metal removal: a review of physical/chemical technologies and
      field applications.
AB  - Soil washing is one of the few permanent treatment alternatives to remove metal
      contaminants from soils. This paper reviews the various technology types and
      pilot/full-scale field applications of soil washing applicable to soils highly
      contaminated with heavy metals. The physical separation technologies, the
      chemical extraction processes and the integrated processes that combine both
      physical and chemical methods are discussed separately. This paper reviews basic
      principles, applicability, advantages and limitations, methods of predicting and
      improving performance of each physical/chemical technology. The discussion is
      based on a review of 30 recent laboratory investigations and 37 field
      applications of soil washing systems which have been undertaken, mostly in the
      US, for the period 1990-2007. This paper also examines and compares the status of
      soil washing technology for remediation of soils contaminated with metals in the
      US, in Canada and in Europe.

PMID- 18036736
TI  - High temperature behavior of electrostatic precipitator ash from municipal solid
      waste combustors.
AB  - Municipal solid waste (MSW) flue gas residues require further treatment prior to
      disposal or reuse, and vitrification is one of the main solidification
      stabilization processes. This paper investigates the high temperature behavior of
      MSW flue gas residues, performed in laboratory experiments up to 1400 degrees C,
      and coupled with thermogravimetric analyses, X-ray diffraction, chemical and
      electron microprobe analyses. Melting temperatures of electrostatic precipitator
      (ESP) ash are in the range of 1202-1272 degrees C, whereas semi-dry scrubber
      residues melt between 1900 and 2300 degrees C. We show that the mean liquidus
      temperature of flue gas residues can be simply evaluated from their CaO content,
      by using the CaOSiO2Al2O3 ternary diagram. For ESP ash, the liquidus phase is a
      Zn-rich aluminous spinel, followed by anorthite at 1225 degrees C, and melilite
      at 1190 degrees C. The total mass loss reaches 18 wt.% at 1300 degrees C.
      Moreover, 90% of evaporation takes place below 1000 degrees C, linked to
      evaporation of C, Cl, S, Na, K, and of the toxic metals Hg, Cd, Pb, Cu. Due to
      the high partial pressure of chlorine during heating, chloride is the most
      probable form of evaporation for Cd, Pb, and Cu. However, most of Zn, Cr, Ni, Sb
      and Sn remain in the vitrified product.

PMID- 18036737
TI  - Treatment of leachate by electrocoagulation using aluminum and iron electrodes.
AB  - In this paper, treatment of leachate by electrocoagulation (EC) has been
      investigated in a batch process. The sample of leachate was supplied from Odayeri
      Landfill Site in Istanbul. Firstly, EC was compared with classical chemical
      coagulation (CC) process via COD removal. The first comparison results with 348
      A/m2 current density showed that EC process has higher treatment performance than
      CC process. Secondly, effects of process variables such as electrode material,
      current density (from 348 to 631 A/m2), pH, treatment cost, and operating time
      for EC process are investigated on COD and NH4-N removal efficiencies. The
      appropriate electrode type search for EC provided that aluminum supplies more COD
      removal (56%) than iron electrode (35%) at the end of the 30 min operating time.
      Finally, EC experiments were also continued to determine the efficiency of
      ammonia removal, and the effects of current density, mixing, and aeration. All
      the findings of the study revealed that treatment of leachate by EC can be used
      as a step of a joint treatment.

PMID- 18036738
TI  - Spatial distribution of particulate matter (PM10 and PM2.5) in Seoul Metropolitan
      Subway stations.
AB  - The aims of this study are to examine the concentrations of PM10 and PM2.5 in
      areas within the Seoul Metropolitan Subway network and to provide fundamental
      data in order to protect respiratory health of subway workers and passengers from
      air pollutants. A total of 22 subway stations located on lines 1-4 were selected
      based on subway official's guidance. At these stations both subway worker areas
      (station offices, rest areas, ticket offices and driver compartments) and
      passengers areas (station precincts, subway carriages and platforms) were the
      sites used for measuring the levels of PM. The mean concentrations of PM10 and
      PM2.5 were relatively higher on platforms, inside subway carriages and in driver
      compartments than in the other areas monitored. The levels of PM10 and PM2.5 for
      station precincts and platforms exceeded the 24-h acceptable threshold limits of
      150 microg/m3 for PM10 and 35 microg/m3 for PM2.5, which are regulated by the
      U.S. Environmental Protection Agency (EPA). However, levels measured in station
      and ticket offices fell below the respective threshold. The mean PM10 and PM2.5
      concentrations on platforms located underground were significantly higher than
      those at ground level (p<0.05).

PMID- 18036739
TI  - Uncooled infrared imaging device based on optimized optomechanical micro
      cantilever array.
AB  - It is a major issue to improve the thermo-mechanical sensitivity of uncooled
      optomechanical focal plane arrays (FPAs) for infrared imaging. This work presents
      an optimized multi-fold interval metallized leg (IML) configuration to increase
      the thermo-mechanical sensitivity of an uncooled optomechanical bi-material micro
      cantilever array. The inclination angle changes of the cantilever elements are
      measured in the IR imaging system using an optical readout with a knife-edge
      filtering operation in the spectrum plane. The multi-fold IML configuration
      consists of alternately connected unmetallized and metallized legs. With the
      optimized fold number, the thermo-mechanical sensitivity of a micro-cantilever
      array can be amplified to two times of one-fold IML for a 120 microm x 120 microm
      element with 1 microm thick SiNx/0.2 microm thick Au films. Room temperature
      objects are imaged with the fabricated FPA containing 160 x 160 elements and a 12
      bit CCD. Further modeling analysis shows that the experimental results are well
      accordant with the theoretical calculation. An important practical feature of the
      implemented approach is its straightforward fabrication for a large FPA, without
      growing complexity and cost.

PMID- 18036740
TI  - Microscopic tomography with ultra-HVEM and applications.
AB  - The ultra-HVEM with an accelerating voltage of 3 MV at Osaka University is
      capable of achieving excellent penetration and resolution for thick specimens. We
      obtained images of 5-microm-thick slices tilted at angles of up to 70 degrees for
      biological samples and observed stick-shaped samples of Si devices free from
      missing zone. These features make the ultra-HVEM an invaluable extension of 3D
      observation by electron tomography. In this paper, we introduce aspects of ultra
      HVEM tomography; specifically, the magnification, the amount of image blurring
      for thick samples and the electron staining method. Finally, we give some typical
      applications in the fields of cell biology, pathology and electrical engineering.

PMID- 18036741
TI  - Maximum diameter of the rod-shaped specimen for transmission electron
      microtomography without the "missing wedge".
AB  - In our recent study, the complete rotation of a rod-shaped specimen during
      transmission electron microscopy (TEM) has been successfully carried out,
      yielding a truly quantitative three-dimensional (3D) structure of a
      ZrO(2)/polymer nano-composite. This result allows the further development of
      transmission electron microtomography (TEMT) for materials science. The diameter
      of the rod-shaped specimen was about 150 nm, which may not be statistically large
      enough to evaluate structural parameters, e.g., volume fraction of Zr nano
      particles. Thus, it is preferable to image rods with larger diameters in 3D. In
      this study, several rod-shaped specimens whose diameters ranged from 150 to 530
      nm were subjected to the "distortion-free TEMT". The maximum diameters, l,
      observable under 200 and 300 kV-TEMTs were, respectively, 460-470 and 600-670 nm
      (corresponding the maximum relative diameters, l/lambda (lambda: mean free path),
      were ca. 2.2 and 2.7-3.0).

PMID- 18036742
TI  - The Fresnel effect of a defocused biprism on the fringes in inelastic holography.
AB  - We present energy filtered holography experiments on a thin foil of Al. By
      propagating the reduced density matrix of the probe electron through the
      microscope, we quantitatively predict the fringe contrast as a function of energy
      loss. Fringe contrast simulations include the effect of Fresnel fringes created
      at the edges of the defocused biprism, the effect of partial coherence in
      combination with inelastic scattering, and the effect of a finite energy
      distribution of the incoming beam.

PMID- 18036743
TI  - Hair straighteners: a significant burn risk.
AB  - BACKGROUND AND AIM: Hair straighteners have become increasingly common household
      appliances. The purpose of this study was to investigate the temperatures reached
      by the exposed plates of hair straighteners when switched on, and the length of
      time taken to cool to a safe temperature after switching off. We also present the
      case of a child with deep dermal burns caused by a hair straightener,
      highlighting its potential danger when left unattended. METHODS: Eight different
      hair straighteners were tested using a calibrated thermometer. Maximum
      temperature reached and length of time taken to cool to 40 degrees C were
      recorded three times for each straightener. RESULTS: Among the eight
      straighteners tested, the size of the plates varied between 22.5 and 53.9cm(2).
      Plate material was ceramic in all but one case. Average maximum temperature was
      163 degrees C (122-210 degrees C). Mean time taken to cool to 40 degrees C from
      switch-off was 26min (18-44min). None of the devices tested could be locked
      closed. DISCUSSION AND CONCLUSION: Hair straighteners present a significant risk
      of burn when left unattended, both while switched on and for up to 44min after
      turning off. We offer some recommendations to improve safety.

PMID- 18036744
TI  - Effects of compressive vests on pulmonary function of infants with thoracic burn
      scars.
AB  - OBJECTIVE: To prospectively evaluate the effects of compressive vests on the
      pulmonary function of infants with thoracic burn scars. METHODS: Between April
      2000 and October 2005, all infants aged 2 years or less and all those aged
      between 2 and 3 years if they had concomitant pulmonary pathology, who were in
      need of a compressive vest for the treatment of burn scars to the thorax,
      underwent comparative pulmonary function testing under sedation with the vest
      closed and then opened. RESULTS: Of the 23 infants who met the inclusion
      criteria, 19 had complete data. There were significant differences in oxygen
      saturation, respiratory rate, tidal volume/kg body weight, respiratory compliance
      and peak tidal expiratory flow /tidal volume, with or without vest compression.
      CONCLUSIONS: Compressive vests used at our centre to treat thoracic burn scars of
      infants aged 2 years or less, and those aged between 2 and 3 years with
      concomitant pulmonary pathology, did have a statistically significant effect on
      their pulmonary function, but this did not translate into clinically significant
      differences. However, the differences observed might become clinically
      significant in the presence of pulmonary comorbidity or severe burns. Routine
      pulmonary function testing before the use of vest compression might thus benefit
      these infants.

PMID- 18036745
TI  - [Pathophysiology of preeclampsia].
AB  - Preeclampsia is a human disease, usually occurring during the third trimester of
      pregnancy. The underlying pathogenetic mechanisms of preeclampsia are much
      debated. Current hypotheses include placental dysfunction, inflammatory disease,
      genetic predisposition and immune maladaptation. Recent studies highlight the
      role of vascular-mediated factors in the pathophysiology of preeclampsia and
      allow new hopes for screening and therapeutic approaches. This article describes
      pathophysiological mechanisms involved in the defective uteroplacental
      vascularization leading to placental and endothelial dysfunction.

PMID- 18036746
TI  - [Amniocentesis practice assessment of the south-west Francilian network during
      2003].
AB  - OBJECTIVES: To assess amniocentesis practice of a network during one year.
      MATERIALS AND METHODS: In a retrospective multicenter study of the south-west
      Francilian network, we have enrolled 2400 patients who underwent amniocentesis,
      from 1 January 2003 to 31 December 2003. RESULTS: The rate of amniocentesis was
      9.5%. The most frequent indication was a positive maternal serum screening test
      result (44%). The rate of global fetal losses (spontaneous miscarriage and
      intrauterine death) was 1.4%. Once the fetuses with aneuploidy and lethal
      pathology excluded, the rate of global fetal losses potentially related to
      amniocentesis was 1.21%. The rate of premature rupture of the membranes was 1.12%
      and prematurity affected 6.5% of the living births. CONCLUSION: Our study has
      highlighted several practices of amniocentesis within the network. Overall,
      amniocentesis potentially induces 1.12% of fetal losses. Screening tests are
      currently used sequentially, which leads to an increase number of amniocentesis
      and to an increase number of losses of "a priori" healthy fetus. Only the use of
      a combined screening could lower the frequency of amniocentesis without
      decreasing the detection rate of chromosome abnormalities.

PMID- 18036747
TI  - [Uterine electromyogram: principle and interest in the diagnosis of preterm
      labour].
AB  - Preterm labour diagnosis rely on clinical arguments exhibiting low positive
      predictive values. Discrimination between uterine contractions leading to preterm
      delivery and physiologic uterine activity increase throughout pregnancy and
      remains difficult. Uterine electrical activity can be recorded non-invasively
      from the abdominal wall and could help in the diagnosis of preterm labour.
      Electrical signal characteristics are reflecting myometrial cells electrical
      properties which are varying throughout pregnancy and labour. During pregnancy,
      uterine electrical activity is very low. During term and preterm labour, uterine
      electrical activity increases as well as mechanical activity. Bursts become
      regular with high amplitude. Spectral analysis demonstrates an increase in the
      frequency content, as represented by the shift of the burst power density
      spectrum peak frequency from low to high frequencies. Consequently, the
      electromyogram signal reflects myometrial excitability and allows differentiating
      powerful uterine contractions leading to delivery from uterine physiologic
      activity. Moreover, electromyogram signal modifications occur before any increase
      in mechanical activity in the pregnant rats, allowing identification of preterm
      labour earlier than uterine mechanical activity measured by intrauterine
      pressure. Two studies performed in women present with preterm contractions are
      supporting the potential interest of the uterine electromyogram recording to help
      in the diagnosis of preterm labour; but further investigations are necessary.

PMID- 18036748
TI  - [Outcome of fetuses with malformations discovered before 14 weeks. Where the
      discovery is revealed by echography during the first trimester, is it responsible
      for the voluntary termination of the pregnancy? Comparison before and after July
      2001].
AB  - OBJECTIVES: The aims of this study were to review detection of fetal
      malformations during the first trimester and to study pregnancy and infant
      outcomes. We wanted to check if the lengthening of the legal delay for volontary
      termination of pregnancy changes the outcome of the pregnancy, in cases outside
      of the legal requirements. MATERIALS AND METHODS: This study was overseen by the
      french college of fetal echography (CFEF). All the cases of abnormality detected
      before 14 weeks' gestational age, excluding the isolated increased nuchal
      translucency, were extracted from the total population examined, and details were
      entered into the database of the French College of Fetal Echography. All case
      records were then analyzed. We compared two populations: before and after July
      2001. RESULTS: We observed 336 fetuses with malformation(s), 108 before July 2001
      and 208 after that date. One percent (0.5-1.6) of scans performed between 10 and
      14 weeks revealed fetal abnormalities apart from isolated increased nuchal
      translucency. Of the 336 cases retained for investigation, 109 increased nuchal
      translucency or hygroma associated with other malformation(s), 103 central
      nervous system anomalies, 85 malformations of the thoracoabdominal wall, 81 limb
      abnormalities, 41 had renal malformations, 28 spinal abnormalities, 21 had heart
      malformations, 16 involved biometric abnormalities, 12 involved abnormalities of
      the appendages, and 11 facial abnormalities. Medical termination of pregnancy was
      performed in 75% of cases. Death in utero occurred in 9% of cases, 12% of infants
      were born alive. In 3.9% of cases, an abortion was performed. There were no
      differences between both populations before and after July 2001. CONCLUSION:
      Excluding isolated increased nuchal translucency or hygroma, malformation before
      14 weeks' gestational age was detected in 1% of fetuses. The most common
      malformations detected in the first trimester were non-isolated increased nuchal
      translucency and malformations of the thoracoabdominal wall and the brain. The
      prognosis for fetuses with malformations detected during the first trimester was
      very poor as only 12% of these infants were born alive, some of them with severe
      malformations. In our study, and given its limitations, there were no differences
      between the number of voluntary terminations performed before and after July
      2001.

PMID- 18036749
TI  - The flexibility thesis: a critique--commentary on Melchers,Shanks and Lachnit.

PMID- 18036750
TI  - Identification of sperm subpopulations with defined motility characteristics in
      ejaculates from Holstein bulls: effects of cryopreservation and between-bull
      variation.
AB  - The aims of the present study were: (1) to determine the existence of sperm
      subpopulations with specific motility characteristics in fresh ejaculates from
      Holstein bulls, (2) to investigate the effects of semen cryopreservation and post
      thaw incubation on the distribution of spermatozoa within the different
      subpopulations, and (3) to evaluate the existence of between-bull variation in
      the sperm subpopulations structure of fresh and frozen-thawed semen. Six
      ejaculates were collected from each of 9 Holstein bulls and cryopreserved
      following a standard protocol. Overall sperm motility and the individual
      kinematic parameters of motile spermatozoa, determined using a CASA system, were
      evaluated before freezing and after 0, 2 and 4h of post-thaw incubation at 37
      degrees C. Data from 16,740 motile spermatozoa, defined by VCL, VSL, VAP, LIN,
      STR, WOB, ALH and BCF, were analysed using a multivariate clustering procedure to
      identify and quantify specific subpopulations within the semen samples. The
      statistical analysis clustered all the motile spermatozoa into four separate
      subpopulations with defined patters of movement: Subpopulation (Subp. 1)
      moderately slow but progressive spermatozoa (23.2%), (Subp. 2) highly active but
      non-progressive spermatozoa (16.0%), (Subp. 3) poorly motile non-progressive
      sperm (35.5%), and (Subp. 4) highly active and progressive sperm (25.3%).
      Subpopulations 2 and 4 significantly (P<0.01) decreased during cryopreservation
      and post-thaw incubation (Subp. 2: 21.1%, 18.1%, 8.7% and 5.9%; and Subp. 4:
      34.1%, 20.6%, 15.2% and 7.3%, respectively, for fresh, 0, 2 and 4h post-thaw)
      whereas Subp. 3 significantly (P<0.01) increased (10.7%, 27.2%, 27.2% and 30.7%,
      respectively, for fresh, 0, 2 and 4h post-thaw). The frequency distribution of
      spermatozoa within subpopulations was quite similar for the 9 bulls, either in
      fresh or frozen-thawed semen, and differences among bulls were mainly due to
      differences in the Subp. 4. Significant correlations (P<0.01) were found between
      the proportions of spermatozoa assigned to Subp. 4 in the fresh ejaculates and
      those in frozen-thawed semen after 0 (r=0.473), 2 (r=0.513) and 4h post-thaw
      (r=0.450). This indicated that the ejaculates with the highest subpopulations of
      rapid and progressive sperm were also the most resistant to cryopreservation and
      showed the best post-thaw sperm longevity.

PMID- 18036751
TI  - Effect of arginine hydrochloride and hydroxypropyl cellulose as stabilizers on
      the physical stability of high drug loading nanosuspensions of a poorly soluble
      compound.
AB  - The objective of the present study is to formulate Naproxen nanosuspensions at
      high drug concentrations of up to 300 mg/ml using ball milling and is to
      investigate the additive effect between hydroxypropyl cellulose (HPC) and
      arginine hydrochloride as stabilizers. The nanosuspensions were obtained at
      different arginine hydrochloride/polymer weight ratios. Stability of Naproxen
      suspensions at 100 and 300 mg/ml was determined over a period of 14 days by
      measuring the particle size. The control, which contained only drug and buffers
      without the stabilizers agglomerated immediately after preparation. The study of
      the effect of arginine hydrochloride as a primary stabilizer indicated that
      arginine hydrochloride levels of up to 0.8% (w/v) were not able to help reduce
      particle size below one micron, and were also not able to provide stabilization
      to the suspensions on storage. Therefore, HPC was also added to the system to
      increase suspensions stability, presumably by a steric repulsion mechanism. When
      the Naproxen concentration was increased to 300 mg/ml, 1% (w/v) HPC was not able
      to provide good stabilization and it was found that arginine hydrochloride
      increased the stabilization efficiency of 1% (w/v) HPC by preventing
      flocculation. When HPC level was increased to 4% (w/v), HPC was high enough to
      sufficiently stabilize the nanosuspensions for 2 weeks and thereby could maintain
      the mean size diameter of the suspensions without the presence of arginine
      hydrochloride. Furthermore, stable nanosuspensions were successfully lyophilized
      without the use of additional cryoprotectants.

PMID- 18036752
TI  - Controlled release of growth hormone from thermosensitive triblock copolymer
      systems: In vitro and in vivo evaluation.
AB  - The purpose of this study was to design injectable controlled release polymer
      formulations for growth hormone using triblock copolymer PLGA-PEG-PLGA (MW 1400
      1000-1400). Porcine growth hormone (pGH) formulations were prepared by adding pGH
      into 30% (w/v) aqueous solution of triblock copolymer. pGH concentrations in the
      released samples were determined using a standard MicroBCA method. In vitro
      release studies demonstrated that there were no initial burst of pGH from both
      formulations containing a low dose (0.12%, w/v) and a high dose (0.42%, w/v) of
      pGH. In vivo absorption study of pGH in rabbits showed that constant serum levels
      of exogenous pGH (3-7 ng/mL from high dose and 2-4 ng/mL from low dose) were
      detected for nearly 4 weeks from delivery systems upon single subcutaneous
      injection. The absolute bioavailability of pGH enhanced from the thermosensitive
      polymer-based systems, which was approximately 5-15-fold those of subcutaneous
      aqueous solution. MTT assay and light microscopy were used to investigate the in
      vitro and in vivo biocompatibility of thermosensitive polymer delivery systems,
      respectively. Both in vitro and in vivo results support the biocompatible nature
      of these polymer delivery systems. Thus, the triblock copolymer used in this
      study was able to control the release of incorporated pGH in vitro and in vivo
      for longer duration and the delivery system was biocompatible.

PMID- 18036753
TI  - The significance of variation in extrusion speeds and temperatures on a PEO/PCL
      blend based matrix for oral drug delivery.
AB  - The body of work described in this research paper outlines the use of PEO/PCL
      blends in the production of monolithic matrices for oral drug delivery. Several
      batches of matrix material were prepared with carvedilol used as the active
      pharmaceutical ingredient. The matrices were prepared using various extrusion
      parameters to investigate the effect of screw speed and barrel temperature on the
      properties of the drug delivery devices. The resultant extrudate was
      characterised using steady state parallel plate rheometry, differential scanning
      calorimetry (DSC) and dissolution testing. Higher screw speeds were observed to
      result in slightly lower matrix melt viscosity when compared with matrices
      compounded using lower screw speeds. Dissolution testing showed that the
      incorporation of the hydrophobic PCL polymer into a PEO matrix results in a
      retarded drug release profile.

PMID- 18036754
TI  - Characteristics of niosomes prepared by supercritical carbon dioxide (scCO2)
      fluid.
AB  - Characteristics of niosomes prepared by a novel supercritical carbon dioxide
      fluid (scCO(2)) technique have been investigated. Niosomes were composed of
      Tween61/cholesterol at 1:0, 3:1, 1:1, 1:3 and 0:1 molar ratios and entrapped with
      d-(+)-glucose by the scCO(2) method without and with ethanol at 5, 10 and 15%
      (w/w) as a co-solvent, and the conventional chloroform film method with
      sonication. Tween61/cholesterol at 1:1 molar ratio niosomes prepared by all
      methods exhibited the best physical stability. Niosomes by the scCO(2) method
      with 10% (w/w) ethanol gave higher trapping efficiency (12.22+/-0.26%) than those
      by the conventional chloroform film method with sonication (10.85+/-0.24%) and
      the scCO(2) method without ethanol (8.40+/-1.60%). Niosomes by the scCO(2) method
      with and without ethanol were large unilamellar structure under TEM with the
      average sizes of 271.9+/-159.6 and 202.5+/-136.7 nm, respectively, whereas those
      by the conventional chloroform film method with sonication were multilamellar and
      unilamellar structure with the average size of 58.4+/-74.6 nm. However, the
      dispersibility of niosomes by the conventional chloroform film method with
      sonication was better than that by the scCO(2) either with or without ethanol,
      because of smaller particle size. This present study has demonstrated the
      trapping efficiency enhancement of water-soluble compounds in niosomes by the
      scCO(2) method with 10% (w/w) of ethanol.

PMID- 18036755
TI  - PLGA/PEG-derivative polymeric matrix for drug delivery system applications:
      Characterization and cell viability studies.
AB  - The incorporation of additives such as polyoxyethylated oleic acid glycerides
      (PEG-derivative) can modify the release of drugs from microparticles. PEG
      derivative decreases the release rate of drugs that are dissolved in PLGA
      matrices but if un-dissolved the initial release rate slightly increases. To
      clarify this behaviour the influence of adding PEG-derivative in the preparation
      of microspheres was investigated by scanning electron microscopy, differential
      scanning calorimetry, gel permeation chromatography, nuclear magnetic resonance
      and infrared spectroscopy. Cytotoxicity of this resulting PLGA/PEG-derivative
      matrix was evaluated in cell lines (fibroblasts) which are more reproducible but
      less specific and in primary cell cultures (splenocytes and human leucocytes)
      which have the advantage of their specificity. Scanning electron microscopy
      revealed that PLGA/PEG-derivative microspheres exhibited small surface
      concavities with a highly porous polymeric matrix. The incorporation of PEG
      derivative caused a slight reduction in the T(g) values of PLGA. In vitro
      degradation studies showed that PEG-derivative remains within the microspheres as
      long as the matrix does. This PLGA/PEG-derivative matrix was well tolerated
      exhibiting cell viabilities similar to PLGA microspheres and can be used to
      modulate the release of drugs from microparticulate systems destined for
      parenteral administration.

PMID- 18036756
TI  - Assessment of the genotoxic risk of Punica granatum L. (Punicaceae) whole fruit
      extracts.
AB  - Punica granatum L. (Punicaceae) whole fruit extracts, have been used in Cuban
      traditional medicine as an effective drug for the treatment of respiratory
      diseases. This species showed interesting anti-viral activity, e.g. aqueous or
      hydroalcoholic extracts of whole fruits have proved highly active against the
      influenza virus. However, some toxic properties of this extract have also been
      reported and, to date, very little is known about its genotoxic properties. In
      the present study, the genotoxicity of a Punica granatum (pomegranate) whole
      fruit extract was assessed using different in vitro and in vivo assays that
      detect DNA damage at different expression levels. Results from reversion and gene
      conversion test in microorganisms, sister chromatid exchanges, micronuclei and
      sperm-shape abnormality assays in mice, clearly showed that the hydroalcoholic
      extract of P. granatum whole fruits is genotoxic when tested both in vitro and in
      vivo.

PMID- 18036757
TI  - An oxcarbazepine-related fatality with an overview of 26 oxcarbazepine postmortem
      cases.
AB  - We present an oxcarbazepine-related fatality together with an overview of 26
      postmortem cases involving oxcarbazepine observed during the period 2001-2006.
      The fatality case concerned a 27-year-old woman with epilepsy, who was found dead
      in her bed. Oxcarbazepine and its active metabolite, 10-hydroxycarbazepine, were
      the only compounds detected. The concentrations of oxcarbazepine were as follows:
      femoral blood, 2.9mg/kg; muscle, 1.8mg/kg; liver, 0.9mg/kg; gastric content
      (300ml), 860mg/kg; and vitreous humour, not detected. The concentrations of 10
      hydroxycarbazepine were as follows: femoral blood, 66mg/kg; muscle, 40mg/kg;
      liver, 62mg/kg; gastric content, 27mg/kg; and vitreous humour, 25mg/kg. The
      analyses were performed by HPLC-DAD after liquid-liquid extraction. Oxcarbazepine
      intoxication was regarded as a possible cause of death. For the other 26 cases,
      the 10-hydroxycarbazepine concentrations ranged from 2.2 to 48mg/kg with a median
      of 25mg/kg.

PMID- 18036758
TI  - Continuous counter current extraction, isolation and determination of solanesol
      in Nicotiana tobacum L. by non-aqueous reversed phase high performance liquid
      chromatography.
AB  - A method of continuous counter current extraction in a large-scale production of
      solanesol from tobacco leaves was developed. The crude extract containing 15-20%
      solanesol was subjected to a series of steps, viz., saponification, solvent
      recrystallization and column chromatography. The pure material was characterized
      by FT-IR, ESI-MS, 1H NMR and 13C NMR spectrometry. The analysis was carried out
      by a simple and rapid non-aqueous reversed-phase high performance liquid
      chromatographic method on a Hypersil BDS C18 column (250 mm x 4.6mm, particle
      size 5 microm) with isopropyl alcohol-methanol (60:40, v/v) as mobile phase and
      detection at 215 nm. The product purity was between 95 and 98% (w/w) as
      determined by HPLC.

PMID- 18036759
TI  - Antimicrobial resistance pattern of Gram-negative bacilli of nosocomial origin at
      2 university hospitals in Iran.
AB  - The purpose of this study was to investigate the antimicrobial resistance pattern
      among common Gram-negative bacilli isolated from patients with nosocomial
      infection. A total of 200 samples of common Gram-negative bacilli (Klebsiella,
      Pseudomonas, Acinetobacter, and Escherichia coli) were collected from 2
      university hospitals in Iran during a 1.5-year period from June 2004 to December
      2005. All samples were examined for the antimicrobial activity of imipenem,
      cefepime, ciprofloxacin, ceftriaxone, and ceftazidime using E-test methods. The
      most frequent pathogens were Klebsiella spp. (38.5%) followed by Pseudomonas
      aeruginosa (28.5%), Acinetobacter spp. (20.5%), and E. coli (12.5%). The most
      active antibiotic was imipenem (84%). The susceptibility of the studied
      microorganisms was 25% for cefepime, 24% for ciprofloxacin, 20.5% for
      ceftazidime, and 11.8% for ceftriaxone. The susceptibility rates of Klebsiella to
      imipenem, cefepime, ciprofloxacin, ceftazidime, and ceftriaxone were 90.9%,
      20.8%, 18.2%, 10.4%, and 5.2%, respectively. Likewise, these rates were 88%, 19%,
      17%, 21%, and 21% for E. coli. Among Acinetobacter spp., the susceptibility rates
      were 77% for imipenem and 21% for ciprofloxacin. Among Pseudomonas, the rates
      were 75% for imipenem and 39% for ciprofloxacin. The antibiotics resistance among
      Gram-negative bacilli was widespread, so an antibiotic policy is urgently needed
      to delay the resistance development.

PMID- 18036760
TI  - First report of qnrB-producing Enterobacter cloacae and qnrA-producing
      Acinetobacter baumannii recovered from Algerian hospitals.
AB  - Two isolates of Enterobacter cloacae and 1 isolate of Acinetobacter baumannii
      showing a multidrug resistance phenotype including resistance to beta-lactams and
      fluoroquinolones were included in this study. By polymerase chain reaction
      amplification and sequencing, the 2 isolates of E. cloacae were found to produce
      QnrB and the A. baumannii isolate was found to produce QnrA. In addition, the 2
      E. cloacae isolates were found to produce CTX-M-15.

PMID- 18036761
TI  - Detection and identification of Candida spp. in human serum by LightCycler real
      time polymerase chain reaction.
AB  - The aim of this work was to develop LightCycler real-time polymerase chain
      reaction method to allow rapid detection and identification of Candida spp. in
      human serum with panfungal primers (internal transcribed spacer [ITS] and L18).
      Melting-curve analysis of the ITS sequences showed that each amplicon presented a
      specific melting point and enabled identification of 5 Candida spp. After
      parameters optimization, 58 sera were preliminary analyzed from 23 patients. For
      L18 primers, the LightCycler system enabled detection of DNA in 92% of patients
      with positive blood culture. These primers were not able to differentiate between
      species of Candida. By using ITS primers, the LightCycler system enabled
      detection of DNA in sera from 76.9% of patients with positive blood culture. With
      ITS primers, the species responsible for the infection was identified for 11
      patients. These data revealed the LightCycler as a potential tool for early
      detection and identification of Candida.

PMID- 18036762
TI  - Quantitative detection of Streptococcus pneumoniae from sputum samples with real
      time quantitative polymerase chain reaction for etiologic diagnosis of community
      acquired pneumonia.
AB  - We assessed the clinical usefulness of a real-time quantitative polymerase chain
      reaction (RQ-PCR) method applied on sputum samples to identify Streptococcus
      pneumoniae in 184 consecutive patients admitted to hospital with community
      acquired pneumonia. Induced sputum samples were analyzed by culture and RQ-PCR.
      In total, 70/184 patients (38%) were diagnosed with S. pneumoniae. Cultures from
      blood and nasopharyngeal secretions were positive in 27/179 (15%) and 42/158
      (27%) cases, respectively. Pneumococcal antigen was detected in 33/169 (20%)
      urine specimens. In sputum samples, culture was significantly positive in 19/128
      (15%), whereas a significant concentration of DNA was found by RQ-PCR in 34/127
      (27%) cases (P < 0.001). In 28/34 (82%) patients with RQ-PCR-positive sputum
      samples, S. pneumoniae was also detected with other methods. In the 34 RQ-PCR
      positive sputum samples, 17 were negative by sputum culture, out of which 14 were
      obtained from patients treated with antibiotics prior to sampling. S. pneumoniae
      may be rapidly diagnosed by analyzing induced sputum samples by RQ-PCR and may be
      particularly valuable in patients in whom antibiotic therapy has been initiated.

PMID- 18036763
TI  - Animal models of neonatal stroke and response to erythropoietin and cardiotrophin
      1.
AB  - Neonatal stroke is increasingly recognized in preterm and term infants, and the
      rate of arterial ischemic infarction occurring around the time of birth is as
      high as the annual incidence of large-vessel ischemic stroke in adults. Thus,
      neonatal stroke is a major contributor to perinatal morbidity and mortality, and
      a considerable number of these children will develop long-term neurodevelopmental
      disabilities. Our ability to investigate this situation has been limited by the
      technical challenges in developing suitable animal models. Our objective is to
      describe recent evidence in relation to animal models of neonatal stroke. In
      addition, we review and report potential neuroprotective strategies specific to
      neonatal stroke, with a focus on erythropoietin and cardiotrophin-1 because of
      their potential role in protection as well as repair.

PMID- 18036764
TI  - The effect of pedometer use in combination with cognitive and behavioral support
      materials to promote physical activity.
AB  - OBJECTIVE: 1. To demonstrate that combining pedometer use with cognitive and
      behavioral support materials has a positive effect on physical activity (PA) and
      attitudes towards pedometer use. 2. To investigate how familiar the study sample
      is with pedometers and the '10,000 steps/day' recommendation. METHODS: From a
      random sample, drawn from the phone book, 304 volunteered (18-75 year) to
      complete a questionnaire about familiarity with pedometers and the '10,000
      steps/day' recommendation. A sample of 103 participants agreed to wear a
      pedometer for 3 weeks, and was randomly assigned to a condition with cognitive
      and behavioral support materials (n=51) or without these materials (n=52).
      Participants completed the International Physical Activity Questionnaire before
      and after 21 days of pedometer use and an additional questionnaire on the
      attitudes towards pedometer use. RESULTS: More than 58% had never heard of a
      pedometer. In both conditions, walking (F=10, p=0.002), moderate PA (F=11,
      p=0.001), and vigorous PA (F=14, p<0.001) increased over time, however no
      interaction effects could be found. Significantly more participants in the
      condition with support materials had a positive attitude towards pedometer use.
      CONCLUSION: Wearing a pedometer, with or without support materials, may increase
      PA. In our study, cognitive and behavioral support materials only affected
      attitudes towards pedometer use. PRACTICE IMPLICATIONS: More research is needed
      to investigate the effect of combining pedometer use with support materials on a
      longer time base and in less motivated people.

PMID- 18036765
TI  - Surgery for hilar cholangiocarcinoma: the Leeds experience.
AB  - AIM: To review the experience with hilar cholangiocarcinoma and to determine the
      results of a radical surgical approach in a UK centre. METHODS: A 10-year review
      of all patients treated surgically for proximal bile duct carcinoma at a single
      surgical unit was conducted. Patient demographics, disease details and
      histopathology reports were reviewed. From January 1993 through December 2003,
      106 patients were admitted with the diagnosis of hilar cholangiocarcinoma and 61
      patients received surgical exploration. RESULTS: Tumours were staged as follows
      (UICC 6th edition): stage IB, n=10 IIA, n=9; IIB, n=20; III, n=8; IV, n=14. Out
      of 61 patients, 44 had a resection (3 bile duct resection alone, 41 liver
      resection with bile duct resection), 5 were considered unresectable and 12
      underwent liver transplantation (LT). The caudate lobe was excised in 34 of the
      patients and regional lymphadenectomy was systematically carried out. Para-aortic
      lymphadenectomy was performed in 17 cases. Portal vein resection was needed in 17
      and hepatic artery resection was performed in 4 cases. Negative histologic
      margins (R0) were achieved in 20 patients and microscopic margin involvement (R1)
      was seen in 16. In the remaining 8 resected patients, localised metastasis were
      found (peritoneal deposits in 2, liver metastasis in 4 and positive para-aortic
      lymph nodes in 2); nevertheless the resection was performed and it was considered
      R2. Overall survival at 3 and 5 years for patients who underwent a resection was
      43% and 28% including postoperative deaths. The 1-, 3- and 5-year actuarial
      survival rates for patients who underwent R0 resection were 78%, 64% and 45%
      respectively, including the postoperative deaths (n=3). The median survival time
      was 41.1 months. The 1-, 3- and 5-year actuarial survival rates for R1 resection
      and R2 were 60%, 26%, 26% and 25% and 0% respectively, while the median survival
      time for these groups was 15.4 and 6.8 months respectively. The actuarial
      survival rate at 1, 3 and 5 years for well-differentiated tumours (G1) was 73%,
      54% and 40% (median 39.7 months). The figures for G2 were 60%, 48% and 0%. The
      figures for G3 (poorly differentiated) were 16% and 0% at three years
      (p=0.03).The overall survival at 3 and 5 years for those patients who had a liver
      transplant was 41% and 20% including early postoperative mortality. The tumour
      grading (presence of poorly differentiated tumour) was found to be the only
      independent factor affecting the survival time producing a hazard ratio of 4.3
      (p=0.0034, 95% confidence interval 0.1007-6.342). CONCLUSIONS: Radical surgical
      resection is the best treatment for hilar cholangiocarcinoma. R0 resection
      provides acceptable 5-year survival, but R1 resection may also provide acceptable
      palliation. In our experience TNM stage and tumour grade were the main
      determinants of long-term survival.

PMID- 18036766
TI  - Increasing long-term survival in advanced colorectal cancer.

PMID- 18036767
TI  - [Long-term management of patients after bariatric surgery].
AB  - Bariatric surgery has developed substantially in France over the past 15 years.
      It has numerous complications that vary according to the type of procedure.
      Adjustable gastric banding and gastric bypass are the most common bariatric
      surgery techniques in France. The adjustable gastric band is particularly subject
      to surgical and mechanical complications long after surgery. Early postoperative
      complications are more frequent after gastric bypass and generally more serious
      than with the gastric band. Longer after surgery, the gastric bypass has
      essentially nutritional complications. The role of the general practitioner is
      fundamental in coordinating follow-up of patients, in collaboration with the
      medical-surgical team that performed the operation. Long-term follow-up of
      patients is essential because of the risk of late complications.

PMID- 18036768
TI  - [Multiple psychoactive substance use (alcohol, tobacco and cannabis) in the
      French general population in 2005].
AB  - OBJECTIVE: To quantify the different forms of polydrug use in the French
      population and the principal factors associated with it. METHODS: Data came from
      the Barometre Sante 2005, a general population study. Polydrug use was approached
      by 2 indicators: regular use of at least 2 products among alcohol, tobacco and
      cannabis, and the use during the year of at least 2 illegal drugs besides
      cannabis (not necessarily concomitantly). RESULTS: Regular use of some
      combination of alcohol, tobacco and cannabis was reported by 8.3% of the
      population. Those aged 20-24 years combined tobacco and cannabis most frequently,
      with 11.6% reporting this joint use. Regular consumption of all 3 products was
      rare, reported by less than 1% of those aged 15-64 years. It was highest among
      those aged 20-29 years, but still less than 2% of the age group. The principal
      combination for those aged 35 years or older was alcohol and tobacco, and those
      in this group rarely combined cannabis with another substance. There was a strong
      association between cannabis use and use of other illicit psychoactive
      substances. Lifetime use of illicit psychoactive substances except for cannabis
      was reported by 10.0% of the 15-34 year-olds; for use during the previous year,
      it was 2.3%. The factors associated with these practices were unemployment, male
      gender, and youth. Postsecondary education appeared to distance young adults from
      the different forms of polydrug use. DISCUSSION: Because use of multiple
      psychoactive substances is often associated with risk-taking or vulnerability,
      particular attention to these practices is justified. Surveys in the general
      population do not cover the most vulnerable or most "desocialized" populations
      and do not allow the most dangerous forms of polydrug use to be described. They
      supply useful information for assessing the extent of the most common combined
      uses in the population and their probable health and social repercussions.

PMID- 18036769
TI  - [Factors associated with delay in calling Emergency Medical Services ("15") for
      patients with ST-elevation myocardial infarction in southern Isere].
AB  - BACKGROUND: Time until revascularization is an important prognostic factor for
      patients with ST-elevation myocardial infarction. The objective of this study was
      to investigate the factors associated with patients' delay in calling for
      emergency medical services (SAMU, "15" in France). METHODS: We analyzed the
      original data of a permanent prospective register of patients receiving care from
      mobile intensive care units staffed by emergency physicians and dispatched by
      SAMU in southern Isere (France), from October 1, 2002, through December 31, 2004.
      RESULTS: Of the 380 patients analyzed, 71% were men and 15% had a history of
      coronary disease. The median age was 60 years for men and 72 for women. The
      median time from symptom onset to calling SAMU was 63 minutes (interquartile
      range, 27 to 144). In the univariate analyses, the time to the call was higher
      for women (90 v 58, p<0.01) and increased with age (p<0.01) and prior calls to a
      physician or nurse (115 v 45, p<0.001). In the multivariable analysis, factors
      independently associated with delay in calling SAMU included female gender, age
      of 55-64 years, prior calls to a physician or nurse, and onset of pain during the
      weekend or at night. The media call delay did not differ for patients with and
      without a history of coronary disease. CONCLUSION: The subpopulations of patients
      characterized by the factors associated with delayed calls should be the target
      of programs to stress the importance of calling SAMU quickly, regardless of the
      time of day; the effectiveness of these programs should be evaluated by
      randomized studies before they enter general use.

PMID- 18036770
TI  - ["Admission letter": an indicator of frailty in elderly emergency department
      patients].

PMID- 18036771
TI  - [Lung function tests in refractory asthma].
AB  - Obstructive airway disorders and bronchial hyperreactivity are part of the
      definition of asthma. Lung function tests (LFT) are therefore essential in the
      diagnosis and follow-up of patients with asthma. Maximum forced expiratory volume
      in one second (FEV1) is the essential functional indicator of severity and
      reversibility, according to the Global Initiative for Asthma (Gina). FEV1 has
      some limitations: it is poorly correlated with dyspnea, symptom control, and lung
      distention. In severe asthma, FEV1 is the only functional indicator included in
      the diagnostic criteria. It is one minor criterion among 2 major and 7 minor
      criteria. Other indicators measured during standard LFT and new functional
      indicators not yet sufficiently validated should provide important supplementary
      information to help to characterize the different clinical phenotypes and the
      pathophysiologic mechanisms involved in refractory asthma.

PMID- 18036772
TI  - [The HIV-infected traveler: infectious risks and prevention].
AB  - Patients with human immunodeficient virus (HIV) must make special preparations
      before traveling. They have a higher risk of infection than the general
      population. They are more likely to develop malaria and the clinical episodes
      will be more severe, particularly in pregnant women. Prescriptions for malaria
      prophylaxis and treatment must take into account their interactions with
      antiretroviral drugs. Vaccination decisions require consideration of the risk and
      severity of the vaccine preventable diseases in the destination area, the nature
      of the vaccine, the patient's immune status, and the risk of virological rebound
      as a consequence of vaccination. Some countries have entry restriction for
      travelers with HIV. Special precautions may be necessary for transporting and
      storing antiretroviral medications.

PMID- 18036773
TI  - [The National Plan for rare diseases, an opportunity for patients].

PMID- 18036774
TI  - Induction of oxidative stress in human Chang liver cells by octachlorostyrene,
      the persistent and bioaccumulative toxicant.
AB  - Octachlorostyrene (OCS) is a persistent and bioaccumulative toxicant (PBT) that
      is a halogenated aromatic compound. OCS belongs to the primary level I group
      chemicals designated by the US Environmental Protection Agency, which are the
      most concerning chemicals among the PBTs. It is known that OCS has never been
      commercially used but has been widely distributed in the environments. Although
      OCS has been occasionally measured in human samples as well as environmental
      samples such as water, soil, sediment, fishes, and marine mammals, the impact of
      OCS on human health is still unclear. It is assumed that the toxicities of OCS
      follow the other chlorinated chemicals, like hexachlorobenzene, and there is also
      possibility to be metabolized to generate radicals. In this study, cell toxicity
      and induction of reactive oxygen species (ROS) by OCS (6.25, 12.5, 25, 50 microM)
      were studied in cultured human Chang liver cells. Exposure of cultured cells to
      OCS led to cell death, ROS increase, and cytosolic caspase-3 activation. ROS
      increase was related to the decreased level of GSH. Chromatin fragmentation and
      condensation were also shown in OCS-treated cells. These results suggest the
      toxicity in the human Chang liver cells by OCS may be induced through the
      apoptotic processes.

PMID- 18036775
TI  - Diploid parthenogenetic embryos adopt a maternal-type methylation pattern on both
      sets of maternal chromosomes.
AB  - Epigenetic modifications are closely associated with embryo developmental
      potential. One of the epigenetic modifications thought to be involved in genomic
      imprinting is DNA methylation. Here we show that the maternally imprinted genes
      Snrpn and Peg1/Mest were nearly unmethylated or heavily methylated, respectively,
      in their differentially methylated regions (DMRs) at the two-cell stage in
      parthenogenetic embryos. However, both genes were gradually de novo methylated,
      with almost complete methylation of all CpG sites by the morula stage in
      parthenogenetic embryos. Unexpectedly, another maternally imprinted gene, Peg3,
      showed distinct dynamics of methylation during preimplantation development of
      diploid parthenogenetic embryos. Peg3 showed seemingly normal methylation
      patterns at the two-cell and morula stages, but was also strongly de novo
      methylated in parthenogenetic blastocysts. In contrast, the paternally imprinted
      genes H19 and Rasgrf1 showed complete unmethylation of their DMRs at the morula
      stage in parthenogenetic embryos. These results indicate that diploid
      parthenogenetic embryos adopt a maternal-type methylation pattern on both sets of
      maternal chromosomes and that the aberrantly homogeneous status of methylation
      imprints may partially account for developmental failure.

PMID- 18036776
TI  - Detection of four beta-thalassemia point mutations in Iranians using a PCR-ELISA
      genotyping system.
AB  - Development of molecular techniques with analytical capability of mutation
      detection can realize the medical diagnosis of diseases and improve people's
      health. beta-Thalassemia is one of the most prevalent genetic disorders in Iran
      and using a simple and rapid test in laboratories for the mass screening and
      prenatal diagnosis is essential. Here, we described a simple method for rapid
      detection of four common beta-thalassemia point mutations in Iranians (IVS-II-1
      (G-->A), IVS-I-5 (G-->C), FSC 8/9 (+G), IVS-I-110 (G-->A)) using a PCR-ELISA
      genotyping system. After DNA isolation from whole blood, a segment of beta-globin
      gene was amplified by DIG-labeling PCR. The DIG-labeled PCR amplicons were
      denatured and added to biotinylated normal probe (for normal gene allele) and
      mutant probe (for mutant gene allele). The hybrids were detected by colorimetric
      ELISA method. The optical densities obtained using normal and mutant probes with
      heterozygous PCR products were very similar. The optical densities obtained using
      mutant probes were higher than normal probes with homozygous PCR products. In
      vice versa, the optical densities obtained using normal probes were higher than
      mutant probes with normal PCR products. All the results demonstrated that the PCR
      ELISA has similar specificity in comparison to the amplification refractory
      mutation system.

PMID- 18036777
TI  - Laryngeal manual therapy: a preliminary study to examine its treatment effects in
      the management of muscle tension dysphonia.
AB  - The objectives of this study were to determine appropriate acoustic and outcome
      measures for the evaluation of a method of laryngeal manual therapy (LMT) used in
      the treatment of patients with muscle tension dysphonia (MTD). The effects of
      this technique were also investigated. The study was based on the hypotheses that
      the vertical position of the larynx in the vocal tract would lower, that the
      quality of the voice would normalize, and that a reduction in any vocal tract
      discomfort (VTD) would occur after LMT. This was a small, prospective, repeated
      measures pilot study in which each member of the research team was "blinded" to
      all other stages of the study and during which all data were anonymized until the
      final stage of data analysis. Ten subjects presenting with MTD completed outcome
      measures and provided audiorecordings immediately before, immediately after, and
      1 week after LMT. The Kay CSL 4150 was used for signal acquisition and for some
      acoustic measurements. Spectrographic evaluation was accomplished with Praat. A
      new perceptual, self-rating scale, the VTD scale, and a new proforma for use by
      the clinician for palpatory evaluation, were developed for the study. Relative
      average perturbation during connected speech was significantly reduced after LMT,
      indicating a reduction in abnormal vocal function. The severity and frequency of
      VTD was shown to have reduced after LMT. This pilot study showed positive
      evidence for LMT as a method of therapy in the treatment of hyperfunctional voice
      disorders. Its effects were shown to be measurable with both acoustical analysis
      and the VTD scale.

PMID- 18036778
TI  - A retrospective study concerning the psychosocial impact of voice disorders:
      Voice Handicap Index change in patients with benign voice disorders after
      treatment (measured with the Dutch version of the VHI).
AB  - The goal of this study was to gain better understanding of psychosocial effects
      of benign voice problems as measured with the Dutch version of the Voice Handicap
      Index (VHI). The effect of voice problems on daily life differs from person to
      person. Over the last few decades there has been a growing understanding of the
      fact that the psychosocial effect of this medical problem needs to be
      acknowledged. The VHI is a known voice specific Quality-of-Life measuring
      instrument, which is often used for this purpose. In the University Medical
      Center Groningen, Groningen, the Netherlands, patients with voice problems are
      analyzed at a Voice Clinic by a multidisciplinary team of voice specialists. In
      this study, we have analyzed patients with benign voice problems before and after
      treatment in the period of April 2004 to October 2006. The study group consisted
      of 68 patients (39 female). For comparison reason, we included a control group
      (n=68), matched for age and gender. The mean VHI score of the patient group
      before treatment was 48.9 (SD=20.9). After treatment, there was a significant
      improvement to 28.3 (SD=20.5) (P<0.001). There was no significant difference
      between the VHI scores of men and women. As could be expected, voice disorders of
      different etiology showed different VHI scores. Before and after treatment, the
      patient group showed a statistically significantly higher VHI score (P<0.001)
      compared with the control group (mean VHI score of 3.62, SD=3.82). Patients with
      different voice problems seem to have different results with the VHI. Treatment
      leads to statistically significant improvement in VHI scores. The VHI has proven
      to be a good instrument to evaluate the psychosocial consequences of voice
      problems.

PMID- 18036780
TI  - Vertical ramus osteotomy with Er:YAG laser: a feasibility study.
AB  - The general advantages of laser surgery, such as decreased bleeding and dry
      surgical field, reduced postoperative pain and less oedema, have led to a
      continuous interest in laser applications for bone cutting. The ability to cut
      bone with a laser beam would also be of great technical benefit in minimally
      invasive maxillofacial surgery (endoscopic). The Erbium:yttrium aluminum garnet
      (Er:YAG) laser has been demonstrated to result in minimal thermal damage of bone,
      precise cutting, rapid osseous healing and osteoinduction. The purpose of this
      study was to assess the feasibility of using Er:YAG laser to perform vertical
      ramus osteotomy, and to determine the most efficient energy per pulse for its
      completion. Two fresh pig mandibles, one pig cadaver head and one human mandible
      were used. A different energy per pulse (0.5, 1, 1.5 and 2J/pulse) was used for
      each osteotomy on the pig mandibles (n=4). Vertical ramus osteotomy was feasible
      with all energy settings but time decreased considerably from 28 to 5.33 min as
      the energy per pulse increased. The human and the pig cadaver head mandibles were
      osteotomized bilaterally with 2000 mJ/pulse that was the most efficient in terms
      of time. Bone cuts were smooth with no carbonization in all cases.

PMID- 18036779
TI  - FIP200, a key signaling node to coordinately regulate various cellular processes.
AB  - A central question in cell biology is how various cellular processes are
      coordinately regulated in normal cell and how dysregulation of the normal
      signaling pathways leads to diseases such as cancer. Recent studies have
      identified FIP200 as a crucial signaling component to coordinately regulate
      different cellular events by its interaction with multiple signaling pathways.
      This review will focus on the cellular functions of FIP200 and its interacting
      proteins, as well as the emerging roles of FIP200 in embryogenesis and cancer
      development. Further understanding of FIP200 function might provide novel
      therapeutic targets for human diseases such as cancer.

PMID- 18036781
TI  - Blockade of AMPA-receptors attenuates 4-aminopyridine seizures, decreases the
      activation of inhibitory neurons but is ineffective against seizure-related
      astrocytic swelling.
AB  - The neurotransmitter glutamate plays a pivotal role in the development of the
      neuropathological sequelae following acute seizures. Our previous data proved the
      efficacy of the NMDA-receptor antagonists on the symptoms, survival and neuronal
      activation in the 4-aminopyridine- (4-AP) induced seizures. In this study, we
      examined the effects of two different doses of a non-competitive, selective,
      allosteric AMPA-receptor antagonist, GYKI 52466. GYKI 52466 was effective in
      prolonging the latency to generalised seizures and reduction of seizure
      mortality. However, the effects on neuronal c-fos expression and astrocyte
      swelling were complex. The 25mg/kg dose of GYKI 52466 was effective in reducing
      the c-fos immunoreactivity (IR) in the hippocampus only. In the neocortex the
      overall c-fos-IR cell counts were increased significantly. Investigation of the
      neocortical parvalbumin-containing interneuron population proved that GYKI 52466
      decreased c-fos expression. The 50mg/kg dose of GYKI 52466 significantly reduced
      the c-fos-IR in the neo- and allocortex, not only in principal neurons, but also
      in the parvalbumin-positive interneurons. The GYKI 52466-pretreatment did not
      prevent the astrocyte swelling in the investigated cortical areas; thus we
      conclude that the AMPA-receptors have little if any involvement in the in the
      mediation of neuropathological alterations in acute convulsions.

PMID- 18036782
TI  - EM703, the new derivative of erythromycin, inhibits transcription of type I
      collagen in normal and scleroderma fibroblasts.
AB  - BACKGROUND: Excessive accumulation of collagen in the skin and internal organs in
      systemic sclerosis (SSc) is considered to result from enhanced transcription of
      collagen in fibroblasts. Macrolides have been reported to show various
      pharmacological activities. Recently, it was reported that EM703, a new
      derivative of erythromycin, improved bleomycin-induced pulmonary fibrosis in
      mice. OBJECTIVE: Therefore, we attempted to examine the effects of EM703 on the
      type I collagen synthetic activity in normal and SSc dermal fibroblasts. METHODS:
      Normal and SSc dermal fibroblasts were cultured with various concentrations of
      Erythromycin A or EM703 for 48h. Amount of type I collagen in the culture medium
      was measured with ELISA with anti-type I collagen antibody. Type I collagen mRNA
      levels were measured by northern blots analysis and type I collagen transcription
      and regulation of the human COL1A1 promoter activity were examined by transient
      transfection and luciferase assay. Electrophoretic gel mobility shift assay was
      also performed for measurement of binding activities of DNA binding factors to
      the COL1A1 promoter. RESULTS: We found that EM703 reduced collagen production and
      the mRNA levels of alpha1(I) collagen in a dose-dependent manner in the normal
      fibroblasts. The transcription of COL1A1 was downregulated as detected by the
      luciferase assay. The downregulation was also detected using DNA containing
      various short lengths of the COL1A1 promoter region. EM703 did not inhibit COL1A1
      transcription when the luciferase assay was performed using DNA containing the
      COL1A1 promoter with a short substitution mutation of the CCAAT box. Decreased
      production of type I collagen at the transcriptional level was also found in SSc
      fibroblasts treated with EM703. CONCLUSION: These results suggest that EM703
      inhibits the transcription of type I collagen in both normal and SSc fibroblasts,
      and that the transcription is inhibited through the CCAAT box of the COL1A1
      promoter.

PMID- 18036783
TI  - Two novel splice mutations of P gene in a Thai-Chinese patient with
      oculocutaneous albinism type II (OCA2).

PMID- 18036784
TI  - A screen for genes that function in leg disc regeneration in Drosophila
      melanogaster.
AB  - Many diverse animal species regenerate parts of an organ or tissue after injury.
      However, the molecules responsible for the regenerative growth remain largely
      unknown. The screen reported here aimed to identify genes that function in
      regeneration and the transdetermination events closely associated with imaginal
      disc regeneration using Drosophila melanogaster. We screened a collection of 97
      recessive lethal P-lacZ enhancer trap lines for two primary criteria: first, the
      ability to dominantly modify wg-induced leg-to-wing transdetermination and
      second, for the activation or repression of the lacZ reporter gene in the
      blastema during disc regeneration. Of the 97 P-lacZ lines, we identified six
      genes (Kruppel-homolog-1, rpd3, jing, combgap, Aly and S6 kinase) that met both
      criteria. Five of these genes suppress, while one enhances, leg-to-wing
      transdetermination and therefore affects disc regeneration. Two of the genes,
      jing and rpd3, function in concert with chromatin remodeling proteins of the
      Polycomb Group (PcG) and trithorax Group (trxG) genes during Drosophila
      development, thus linking chromatin remodeling with the process of regeneration.

PMID- 18036785
TI  - Kruppel homolog 1 (Kr-h1) mediates juvenile hormone action during metamorphosis
      of Drosophila melanogaster.
AB  - Juvenile hormone (JH) given at pupariation inhibits bristle formation and causes
      pupal cuticle formation in the abdomen of Drosophila melanogaster due to its
      prolongation of expression of the transcription factor Broad (BR). In a
      microarray analysis of JH-induced gene expression in abdominal integument, we
      found that Kruppel homolog 1 (Kr-h1) was up-regulated during most of adult
      development. Quantitative real-time PCR analyses showed that Kr-h1 up-regulation
      began at 10h after puparium formation (APF), and Kr-h1 up-regulation occurred in
      imaginal epidermal cells, persisting larval muscles, and larval oenocytes.
      Ectopic expression of Kr-h1 in abdominal epidermis using T155-Gal4 to drive UAS
      Kr-h1 resulted in missing or short bristles in the dorsal midline. This phenotype
      was similar to that seen after a low dose of JH or after misexpression of br
      between 21 and 30 h APF. Ectopic expression of Kr-h1 prolonged the expression of
      BR protein in the pleura and the dorsal tergite. No Kr-h1 was seen after
      misexpression of br. Thus, Kr-h1 mediates some of the JH signaling in the adult
      abdominal epidermis and is upstream of br in this pathway. We also show for the
      first time that the JH-mediated maintenance of br expression in this epidermis is
      patterned and that JH delays the fusion of the imaginal cells and the
      disappearance of Dpp in the dorsal midline.

PMID- 18036786
TI  - Dispensability of nanos mRNA localization for abdominal patterning but not for
      germ cell development.
AB  - The development of a functional germline is essential for species propagation.
      The nanos (nos) gene plays an evolutionarily conserved role in germline
      development and is also essential for abdominal patterning in Drosophila. A small
      fraction of nos mRNA is localized to the germ plasm at the posterior pole of the
      Drosophila embryo, where it becomes incorporated into the germ cells. Germ plasm
      associated nos mRNA is translated to produce a gradient of Nos protein that
      patterns the abdomen, whereas the remaining unlocalized RNA is translationally
      repressed to allow anterior development. Using transgenes that compromise nos
      mRNA localization and translational regulation, we show that wild-type body
      patterning can ensue without nos mRNA localization provided that nos translation
      is properly modulated. In contrast, localization of nos to the germ plasm, but
      not translational regulation, is essential for nos function in the developing
      germ cells. We propose that an imperative for nos localization in producing a
      functional germline has preserved an inefficient localization mechanism.

PMID- 18036787
TI  - Expression of Siamois and Twin in the blastula Chordin/Noggin signaling center is
      required for brain formation in Xenopus laevis embryos.
AB  - The blastula Chordin- and Noggin-expressing (BCNE) center located in the dorsal
      animal region of the Xenopus blastula embryo contains both prospective anterior
      neuroectoderm and Spemann organizer precursor cells. Here we show that, contrary
      to previous reports, the canonical Wnt target homeobox genes, Double knockdown of
      these genes using antisense morpholinos in Xenopus laevis blocked head formation,
      reduced the expression of the other BCNE center genes, upregulated Bmp4
      expression, and nullified hyperdorsalization by lithium chloride. Moreover, gain-
      and loss-of-function experiments showed that Siamois and Twin expression is
      repressed by the vegetal transcription factor VegT. We propose that VegT
      expression causes maternal beta-Catenin signals to restrict Siamois and Twin
      expression to the BCNE region. A two-step inhibition of BMP signals by Siamois
      and Twin-- first by transcriptional repression of Bmp4 and then by activation of
      the expression of the BMP inhibitors Chordin and Noggin--in the BCNE center is
      required for head formation.

PMID- 18036788
TI  - Spectral force analysis using atomic force microscopy reveals the importance of
      surface heterogeneity in bacterial and colloid adhesion to engineered surfaces.
AB  - Coatings developed to reduce biofouling of engineered surfaces do not always
      perform as expected based on their native properties. One reason is that a
      relatively small number of highly adhesive sites, or the heterogeneity of the
      coated surface, may control the overall response of the system to initial
      bacterial deposition. It is shown here using an approach we call spectral force
      analysis (SFA), based on force volume imaging of the surface with atomic force
      microscopy, that the behavior of surfaces and coatings can be better understood
      relative to bacterial adhesion. The application of vapor deposited TiO(2) metal
      oxide increased bacterial and colloid adhesion, but coating the surface with
      silica oxide reduced adhesion in a manner consistent with SFA based on analysis
      of the "stickiest" sites. Application of a TiO(2)-based paint to a surface
      produced a relatively non-fouling surface. Addition of a hydrophilic layer
      coating to this surface should have decreased fouling. However, it was observed
      that this coating actually increased fouling. Using SFA it was shown that the
      reason for the increased adhesion of bacteria and particles to the hydrophilic
      layer was that the surface produced by this coating was highly heterogeneous,
      resulting in a small number of sites that created a stickier surface. These
      results show that while it is important to manufacture surfaces with coatings
      that are relatively non-adhesive to bacteria, it is also essential that these
      coatings have a highly uniform surface chemistry.

PMID- 18036789
TI  - Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta
      cyclodextrin inclusion complex.
AB  - Ropivacaine (RVC) is an enantiomerically pure local anesthetic (LA) largely used
      in surgical procedures, which presents physico-chemical and therapeutic
      properties similar to those of bupivacaine (BPV), but associated to less systemic
      toxicity. This study focuses on the development and pharmacological evaluation of
      a RVC in 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) inclusion complex. Phase
      solubility diagrams allowed the determination of the association constant between
      RVC and HP-beta-CD (9.46 M(-1)) and showed an increase on RVC solubility upon
      complexation. Release kinetics revealed a decrease on RVC release rate and
      reduced hemolytic effects after complexation (onset at 3.7 mM and 11.2mM for RVC
      and RVC HP-beta-CD, respectively) were observed. Differential scanning
      calorimetry (DSC), scanning electron microscopy (SEM) and X-ray analysis (X-ray)
      showed the formation and the morphology of the complex. Nuclear magnetic
      resonance (NMR) and job-plot experiments afforded data regarding inclusion
      complex stoichiometry (1:1) and topology. Sciatic nerve blockade studies showed
      that RVC HP-beta-CD was able to reduce the latency without increasing the
      duration of motor blockade, but prolonging the duration and intensity of the
      sensory blockade (p<0.001) induced by the LA in mice. These results identify the
      RVC HP-beta-CD complex as an effective novel approach to enhance the
      pharmacological effects of RVC, presenting it as a promising new anesthetic
      formulation.

PMID- 18036790
TI  - Bayesian modeling of dynamic motion integration.
AB  - The quality of the representation of an object's motion is limited by the noise
      in the sensory input as well as by an intrinsic ambiguity due to the spatial
      limitation of the visual motion analyzers (aperture problem). Perceptual and
      oculomotor data demonstrate that motion processing of extended objects is
      initially dominated by the local 1D motion cues, related to the object's edges
      and orthogonal to them, whereas 2D information, related to terminators (or edge
      endings), takes progressively over and leads to the final correct representation
      of global motion. A Bayesian framework accounting for the sensory noise and
      general expectancies for object velocities has proven successful in explaining
      several experimental findings concerning early motion processing [Weiss, Y.,
      Adelson, E., 1998. Slow and smooth: a Bayesian theory for the combination of
      local motion signals in human vision. MIT Technical report, A.I. Memo 1624]. In
      particular, these models provide a qualitative account for the initial bias
      induced by the 1D motion cue. However, a complete functional model, encompassing
      the dynamical evolution of object motion perception, including the integration of
      different motion cues, is still lacking. Here we outline several experimental
      observations concerning human smooth pursuit of moving objects and more
      particularly the time course of its initiation phase, which reflects the ongoing
      motion integration process. In addition, we propose a recursive extension of the
      Bayesian model, motivated and constrained by our oculomotor data, to describe the
      dynamical integration of 1D and 2D motion information. We compare the model
      predictions for object motion tracking with human oculomotor recordings.

PMID- 18036791
TI  - Question of dose, fractionation and technique: ingredients for testing
      hypofractionation in prostate cancer--the CHHiP trial.

PMID- 18036792
TI  - An investigation into the effects of thermal history on the crystallisation
      behaviour of amorphous paracetamol.
AB  - The effects of thermal history and sample preparation on the polymorphic
      transformation profile from amorphous paracetamol have been investigated. The
      crystallisation behaviour of slow and quench cooled amorphous paracetamol was
      studied using DSC. Quench cooled paracetamol showed a glass transition (Tg) at
      25.2 degrees C, a single exothermic transition at 64.9 degrees C and an endotherm
      at 167.7 degrees C. The initial degree of crystallinity was calculated as a
      function of time and recrystallisation circa 20 degrees C below Tg was
      demonstrated. Slow cooled material in pinholed or hermetic pans (sealed under
      nitrogen) showed a Tg at 25.1 degrees C, two exothermic transitions at circa 80
      85 degrees C and 120-130 degrees C followed by melting at 156.9 degrees C; a
      single exotherm at 83 degrees C was observed for material sealed in hermetic pans
      under ambient conditions. Hot stage microscopy yielded complementary information
      on crystal growth and transformation profile. A transformation scheme is proposed
      which indicates that amorphous paracetamol may transform into Form III, II or I
      depending on the thermal history and the gaseous environment in which
      recrystallisation takes place. The study has demonstrated that the thermal
      history and encapsulation method may profoundly influence the polymorphic forms
      generated from amorphous paracetamol.

PMID- 18036793
TI  - Influence of formulation and process parameters on the release characteristics of
      ethylcellulose sustained-release mini-matrices produced by hot-melt extrusion.
AB  - Mini-matrices (multiple unit dosage form) with release-sustaining properties were
      developed by hot-melt extrusion (cylindrical die: 3mm) using metoprolol tartrate
      as model drug and ethylcellulose as sustained-release agent. Dibutyl sebacate was
      selected as plasticizer and its concentration was optimized to 50% (w/w) of the
      ethylcellulose concentration. Xanthan gum, a hydrophilic polymer, was added to
      the formulation to increase drug release. Changing the xanthan gum concentration
      modified the in vitro drug release: increasing xanthan gum concentrations (1%,
      2.5%, 5%, 10% and 20%, w/w) yielded a faster drug release. Zero-order drug
      release was obtained at 5% (w/w) xanthan gum. Using kneading paddles, smooth
      extrudates were obtained when processed at 60 degrees C. At least one mixing zone
      was required to obtain smooth and homogeneous extrudates. The mixing efficacy and
      drug release were not affected by the number of mixing zones or their position
      along the extruder barrel. Raman analysis revealed that metoprolol tartrate was
      homogeneously distributed in the mini-matrices, independent of screw design and
      processing conditions. Simultaneously changing the powder feed rate (6-25-50
      g/min) and screw speed (30-100-200 rpm) did not alter extrudate quality or
      dissolution properties.

PMID- 18036794
TI  - Myotoxicity studies of O/W-in situ forming microparticle systems.
AB  - The objective of this study was to investigate the myotoxicity potential of the
      solvents used in the preparation of polymer solutions and O/W-in situ forming
      microparticle (ISM) systems. The acute myotoxicity studies of the tested
      solvents, emulsions of the solvents, polymer solutions as well as the O/W-ISM
      formulations with varying phase ratios were investigated using the in vitro
      isolated rodent skeletal muscle model by measuring the cumulative creatine kinase
      (CK) efflux. Phenytoin and isotonic sodium chloride solution served as positive
      and negative controls, respectively. Results from the in vitro myotoxicity
      studies suggested that the investigated five partially water miscible solvents
      caused muscle damage in the following rank order: benzyl alcohol>triethyl
      citrate>triacetin>propylene carbonate>ethyl acetate. Myotoxicity of ethyl acetate
      was found to be comparable to that of the isotonic sodium chloride solution.
      Emulsions of the undiluted solvents and an aqueous 0.5% Pluronic F 68 solution
      (ratio 1:4) could dramatically reduce the myotoxicities to 24-65%. The
      myotoxicity of O/W-ISM was less than those of the polymer solutions and the
      undiluted solvents. The cumulative CK level from the muscle treated with the O/W
      ISM with phase ratio 1:4 was comparable to those from the negative controls. Area
      under the CK plasma curve from Sprague-Dawley rats was used to evaluate the in
      vivo myotoxicity following an intramuscular injection of the formulations. The in
      vivo myotoxicity data was well correlated with the in vitro myotoxicity data and
      confirmed the good muscle compatibility of the O/W-ISM formulations.

PMID- 18036795
TI  - Postoperative fibromatosis-type fibromas in the Bhd gene mutant (Nihon) rat.
AB  - Fibromatosis-type fibromas were found to develop at abdominal surgical sites in 4
      heterozygous Nihon rats, a model for the human Birt-Hogg-Dube syndrome. In all 4
      rats, solitary and firm nodules were located within the lateral abdominal
      musculature involving the full thickness of the abdominal wall at the sites of
      laparotomy. Histologically, the nodules consisted of well-differentiated
      fibroblastic spindle-shaped cells. These cells were surrounded by large amounts
      of collagen fibers, and appeared to infiltrate within the abdominal musculature.
      A portion of the spindle-shaped cells showed features of myofibroblasts. These
      characteristics are consistent with desmoid tumors in human. Although the
      etiology of desmoid tumors in human remains unclear, they are known to occur in
      association with hormonal factors, surgical trauma, and familial adenomatous
      polyposis. In animals, they have been reported in dogs, cats, horses, and
      genetically modified mouse models for human familial adenomatous polyposis. The
      development of the tumors in the Nihon rats was apparently associated with
      surgical incisions. Genetic factor should be involved in the occurrence of the
      tumor, since it was found only in the Nihon rats among many rats. Our present
      data suggest that Bhd gene mutation is not likely to be a candidate.

PMID- 18036796
TI  - Basic fibroblast growth factor regulates expression of heparan sulfate in human
      periodontal ligament cells.
AB  - Heparan sulfate (HS) proteoglycan is a widely distributed biological molecule
      that mediates a variety of physiological responses in development, cell growth,
      cell migration, and wound healing. We examined the effects of basic fibroblast
      growth factor-2 (FGF-2), which is known to modulate extracellular matrix (ECM)
      production of various cell types, on the production of HS proteoglycan by human
      periodontal ligament (HPDL) cells. We also examined the effects of FGF-2 on the
      expression of syndecans, a major family of membrane-bound HS proteoglycans.
      Treatment of HPDL cells with FGF-2 for 72 h resulted in a pronounced increase in
      the level of HS in the culture supernatant in a dose-dependent manner. However,
      reverse transcription-polymerase chain reaction data (RT-PCR) revealed that FGF-2
      marginally reduced the gene expression of syndecan-1, -2, and -4, and did not
      alter the level of syndecan-3 mRNA. Furthermore, FGF-2 did not have an effect on
      the mRNA expression of enzymes associated with HS biosynthesis. Interestingly,
      FACS analysis revealed that the syndecan family displayed diverse alterations in
      response to FGF-2. FGF-2 barely altered the expression of syndecan-1, but
      decreased the expression of syndecan-2 and -4 on HPDL cells. Moreover, dot blot
      analysis showed that FGF-2 did not alter the level of syndecan-1 and -2, but
      enhanced the level of syndecan-4 in culture supernatants of FGF-2-stimulated HPDL
      cells. These results suggest that the FGF-2-activated increase in the level of HS
      in conditioned medium may be a result of shedding of syndecan-4 from the HPDL
      cell surface. Taken together, FGF-2 may differentially regulate the expression of
      HS proteoglycans in a HS-proteoglycan-subtype-dependent manner. The diversity of
      the expression patterns of HS proteoglycans may be associated with the FGF-2
      induced biological functions of HPDL cells.

PMID- 18036797
TI  - Fatty acid alterations and n-3 fatty acid supplementation in cystic fibrosis.
AB  - Specific fatty acid alterations have been described in the blood and tissues of
      cystic fibrosis (CF) patients. The two most consistent alterations include
      decreased levels of linoleic acid (LA) and decreased levels of docosahexaenoic
      acid (DHA). Increased arachidonic acid (AA) release from membrane phospholipids,
      as well as changes in levels of AA and other monounsaturated and polyunsaturated
      fatty acids (PUFAs) have also been described in CF. Although mechanisms of fatty
      acid alterations have not yet been determined, these alterations may have an
      important role in the progression of the CF disease. There have been several
      clinical trials in which CF patients were supplemented with n-3 fatty acids. Most
      trials resulted in an increase in the levels of the supplemental fatty acids in
      the blood of CF patients in the absence of significant clinical improvement. It
      is recommended that future trials include a larger population of CF patients and
      measure multiple clinical outcomes.

PMID- 18036798
TI  - Cytoprotective effects of phenolic antioxidants and essential fatty acids in
      human blood monocyte and neuroblastoma cell lines: surrogates for neurological
      damage in vivo.
AB  - BACKGROUND: Oxidative stress is implicated in the development of a range of
      neurological diseases. There is increasing interest in the neuroprotective
      efficacy of antioxidants in modulating such processes with at least one
      polyphenolic being tested as a prophylactic in Alzheimer's disease. Beneficial
      effects of adjunctive n-3 polyunsaturated fatty acids with combined intakes of
      vitamin C and E on both the positive and negative symptoms of schizophrenia have
      been reported. Robust in vitro systems are desirable, enabling a mechanistic
      investigation of the molecular mechanisms underpinning such effects and
      identification of further potentially efficacious nutraceuticals. MATERIALS AND
      METHOD: A comparative study employing a human lymphoblastoid cell line derived
      from a subject with early onset schizophrenia, a neuroblastoma IMR-32 cell line
      and the histiocytic lymphoma U937 cell line was undertaken. The cytoprotective
      effects of two phenols in affording protection to cellular DNA from an oxidative
      challenge were assessed in untreated and fatty acid treated cell lines. RESULTS
      AND CONCLUSION: Marked differences in the uptake of fatty acids by the cell types
      were found and the IMR-32 cell line was most susceptible to the oxidant
      challenge. Hydroxytyrosol gave significant cytoprotection in all three-cell lines
      and this possible neuroprotective efficacy warrants further investigation, both
      in vitro and in vivo.

PMID- 18036799
TI  - Effects of gestational age on prostaglandin EP receptor expression and functional
      involvement during in vitro contraction of the guinea pig uterus.
AB  - Prostaglandin E(2) (PGE(2)) exerts diverse biological effects through four G
      protein-coupled cell surface receptor subtypes, EP1-4. This study's objective was
      to characterize EP1-4 receptor mRNA expression within pregnant guinea pig
      myometrium during early implantation stage (gestation day [GD] 6) and late stage
      gestation (GD 50) and evaluate in vitro contractile activity of receptor subtype
      selective agonists. Using RT-PCR, qualitative gene expression patterns of EP2,
      EP3, and EP4 mRNA were detected in the myometrium and remained unchanged between
      the gestational ages. EP1 mRNA remained undetected in pregnant tissue. In vitro
      contractile activity was evaluated in GD 6 and GD 50 myometrium using vehicle and
      EP agonists PGE(2), 17-phenyl trinor PGE(2), sulprostone, misoprostol, and CP
      533,536. All spasmogens in pregnant myometrium were EP1/EP3 selective agonists,
      though likely acting via EP3 receptors in this test model. CP-533,536--a highly
      selective EP2 receptor agonist--and the vehicle failed to induce myometrial
      contraction at both gestational ages.

PMID- 18036800
TI  - Role of RXR in neurite outgrowth induced by docosahexaenoic acid.
AB  - We have previously demonstrated that docosahexaenoic acid (DHA) at low micromolar
      concentrations has a remarkable effect on morphological differentiation of
      hippocampal neurons by increasing the population of neurons with more branches
      and longer neurites. In this study, possible involvement of the retinoid X
      receptor (RXR) in the DHA-induced hippocampal neurite outgrowth was evaluated as
      DHA is an endogenous ligand for RXR. Immunocytochemical examination revealed that
      all RXR isoforms, RXR-alpha, -beta(1), -beta(2), and -gamma, are expressed
      exclusively in neurons with distinctive intracellular distribution. The cell
      based dual luciferase reporter assay indicated that DHA activates RXR-alpha at or
      above 10 microM but not at 1.5 microM where DHA induces neurite outgrowth.
      Arachidonic acid also activated RXR-alpha in a similar concentration range but
      with lower efficacy. Our results suggest that DHA-induced neurite outgrowth may
      not be mediated by direct activation of RXR-alpha, although involvement of other
      isoforms or DHA metabolites cannot be excluded.

PMID- 18036801
TI  - Omega-3 fatty acids and neurological injury.
AB  - Studies with omega-3 polyunsaturated fatty acids (PUFA) have shown that these
      compounds have therapeutic potential in several indications in neurology and
      psychiatry. Acute spinal cord injury (SCI) is an event with devastating
      consequences, and no satisfactory treatment is available at present. The
      pathogenetic mechanisms associated with SCI include excitotoxicity, increased
      oxidation and inflammation. We review here our recent studies, which suggest that
      omega-3 PUFA have significant neuroprotective potential in spinal cord trauma. In
      a first study, we administered an intravenous bolus of alpha-linolenic acid (LNA)
      or docosahexaenoic acid (DHA) 30 min after spinal cord hemisection injury in
      adult rats. The omega-3 PUFA led to increased neuronal and glial survival, and a
      significantly improved neurological outcome. In subsequent studies, we tested DHA
      in a more severe compression model of SCI. We also explored a combined acute and
      chronic treatment regime using DHA. Saline or DHA was administered intravenously
      30 min after compression of the spinal cord. After injury, the saline group
      received a standard control diet, whereas DHA-injected animals received either a
      control or a DHA-enriched diet for 6 weeks following injury. We assessed
      locomotor recovery and analysed markers for cell survival and axonal damage, and
      we also investigated the effects of the treatment on the inflammatory reaction
      and the oxidative stress that follow SCI. We showed that the acute DHA treatment
      is neuroprotective after compression SCI, even if the treatment is delayed up to
      an hour after injury. The DHA injection led to an increased neuronal and glial
      cell survival, and the effect of the DHA injection was amplified by addition of
      DHA to the diet. Rats treated with a DHA injection and a DHA-enriched diet
      performed significantly better at 6 weeks in terms of neurological outcome. The
      analysis of the tissue after DHA administration showed that the fatty acid
      significantly reduced lipid peroxidation, protein oxidation and RNA/DNA
      oxidation, and the induction of COX-2. Parallel studies in a facial nerve injury
      model in mice also showed pro-regenerative effects of chronic dietary
      administration of DHA after nerve lesion. These observations suggest that
      treatment with omega-3 PUFA could represent a promising therapeutic approach in
      the management of neurological injury.

PMID- 18036802
TI  - Heparin, lipoproteins, and oxygenated fatty acids in blood: a cautionary note.
AB  - We measured 16 nonesterified oxygenated fatty acid derivatives (oxylipids) in
      plasmas from seven human subjects. Two arterial samples from each subject were
      analyzed, drawn approximately 2h apart. We observed a marked increase in levels
      of most oxylipids in the second sample, as high as 470-fold. Between the first
      and second samples, subjects received approximately 800-1000 IU of heparin to
      prevent clotting in intravascular catheters. We postulate that heparin activated
      lipoprotein lipases, which, in turn, released oxylipids from triglycerides and
      phospholipids in plasma lipoproteins. Some of that lipolysis may have occurred
      during sample storage. Measurements of nonesterified lipids in human plasma may
      be distorted if heparin is administered to subjects before blood is drawn and if
      lipase inhibitors are omitted from stored samples.

PMID- 18036803
TI  - Regulation of adhesion molecule expression in human endothelial and smooth muscle
      cells by omega-3 fatty acids and conjugated linoleic acids: involvement of the
      transcription factor NF-kappaB?
AB  - We previously showed conjugated linoleic acids (CLA) inhibited TNF-alpha-induced
      monocyte (THP-1) adhesion to human umbilical vein endothelial cells (HUVEC) in
      vitro which involved an increase in platelet activating factor (PAF). Here we
      show adhesion molecule (ADM) regulation by fatty acids and the differing role of
      nuclear factor kappa B (NF-kappaB) activation in HUVEC and vascular smooth muscle
      cells (vSMC). CLA and omega-3 long-chain polyunsaturated fatty acids (PUFA) (FA)
      reduced TNF-alpha-induced expression of ADMs (intercellular adhesion molecule-1
      (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1) but not E-selectin) on HUVEC
      and vSMC to different extents depending on FA type and concentration, cell type
      and method of analysis. IkappaBalpha phosphorylation in HUVEC and vSMC and
      transient transfection with NF-kappaB-luciferase reporter plasmid (HUVEC only)
      indicated differential NF-kappaB involvement during FA modulation (cis-9, trans
      11; trans-10, cis-12 and a 50:50 mix of both CLA isomers; eicosapentaenoic acid
      (EPA); docosahexaenoic acid (DHA)). TNF-alpha-induced ADM expression in both cell
      types by 2-10-fold. In HUVEC, CLA t10, c12 and CLA mix (50:50 mixture of CLA c9,
      t11 and t10, c12) and EPA and DHA reduced ICAM-1 expression (15-35%) at 12.5, 25
      and/or 50 microM. VCAM-1 expression was reduced by 25 microM t10, c12 isomer and
      mix; omega-3 PUFA and other concentrations of CLA and TNF-alpha-induced E
      selectin expression were unaffected. TNFalpha-induced inhibitor kappa B (IkappaB)
      phosphorylation was biphasic peaking at 5 min in both cell types and 60 and 120
      min in HUVEC and SMC, respectively. IkappaBalpha phosphorylation and NF-kappaB
      activity was reduced (29% and 30%, respectively) by 25 microM CLA mix. n-3 PUFA
      did not reduce IkappaBalpha phosphorylation or NF-kappaB activity but reduced ADM
      expression. We show that n-3 PUFA and CLA reduce expression of ADM on HUVEC and
      vSMC. This reflected reduced adherence of monocytes to HUVEC previously reported
      by our group. Reduction of ICAM-1 and VCAM-1 protein expression by n-3 PUFA was
      less dependent on the NF-kappaB pathway than reduction by CLA which reflected the
      parallel attenuation of NF-kappaB activity. This indicated involvement of other
      transcription factors (i.e. AP-1) in the FA regulation of ADM expression and has,
      to our knowledge, not been previously reported.

PMID- 18036804
TI  - Unresolved issues in the link between docosahexaenoic acid and Alzheimer's
      disease.
AB  - Lower consumption of docosahexaenoic acid (DHA) is commonly but not always
      associated with higher risk of cognitive decline and diagnosis of Alzheimer's
      disease (AD). We review here the available data relating DHA to AD, with emphasis
      on DHA content of plasma and brain. Our assessment of this literature is that low
      DHA is not consistently observed in AD plasma or brain. However, in dietary and
      population studies, low DHA intake is usually associated with low plasma DHA.
      Therefore, at present, there is no clear explanation of why the usual low DHA
      intake-low plasma DHA relationship appears not to exist in AD. Adding to the
      confusion, preliminary and inconclusive reports tentatively suggest that dietary
      DHA could potentially reduce cognitive deterioration in AD. These inconsistencies
      between dietary DHA, plasma/tissue DHA, and possible DHA efficacy in AD may be
      more methodological than biological, and may arise in part because only one study
      to date has reported both DHA intake and plasma DHA values in the same AD
      patients. Studies reporting DHA intake and plasma levels while also undertaking a
      DHA intervention in AD would presumably help resolve these issues.

PMID- 18036805
TI  - Microarray-based identification of novel biomarkers in IL-1-mediated diseases.
AB  - Interleukin 1b (IL-1b) is emerging as mediator of a wide range of human diseases.
      Availability of IL-1 blockers that result in clinical benefits to patients with
      these diseases is creating a demand for biomarkers to diagnose as well as to
      predict and follow responses to therapy. Blood gene expression profiling can be
      used to identify such biomarkers. This review will summarize recent studies in
      the field and will discuss some of the challenges raised by the use of this
      technology in biomarker discovery.

PMID- 18036806
TI  - The role of E3 ligases in autoimmunity and the regulation of autoreactive T
      cells.
AB  - The ubiquitination of proteins by E3 ligases has become an important regulatory
      mechanism for a variety of immune functions, including the maintenance of self
      tolerance and suppression of autoreactive T cell development. This review
      highlights recent advances in our knowledge of the functions in this context of
      known and potential E3 ligases, including autoimmune regulator (AIRE), TNF
      receptor-associated factor 6 (TRAF6), Casitas B cell lymphoma b (Cbl-b), gene
      related to anergy in lymphocytes (GRAIL), Itch, and Roquin. We discuss how
      disruptions to these molecules may contribute to the loss of T cell homeostasis
      and the pathogenesis of autoimmunity. We also report on the implications of the
      potential coordinated actions of these molecules for T cell anergy and regulatory
      T cell (Treg) functions. The great diversity of E3 ligases and the growing list
      of cellular processes in which ubiquitination plays a role make for an exciting
      field of research. Findings emerging from these investigations may suggest ways
      to exploit the therapeutic potential of manipulating ubiquitination, particularly
      for autoimmune disorders.

PMID- 18036807
TI  - Therapeutics effect of N-acetyl cysteine on mustard gas exposed patients:
      evaluating clinical aspect in patients with impaired pulmonary function test.
AB  - AIMS: Long-term prescription of N-acetyl cysteine (NAC) may be effective in
      diseases caused by active radicals of oxygen species. The aim of this study was
      to determine the effect of 2- and 4-month administration of NAC (1800 mg daily)
      on mustard induced bronchiolitis obliterans. METHODS AND MATERIALS: In a double
      blind clinical trial, 144 patients with bronchiolitis obliterans due to sulfur
      mustard in bronchiolitis obliterans syndrome (BOS) classes 1 and 2, randomly
      entered Group 1 (n=72, NAC) and Group 2 (n=72, placebo). Dyspnea, wake-up
      dyspnea, cough, and sputum were measured after 4 months. Spirometric findings
      were measured at the beginning of the trial, 2 months after and after 4 months of
      prescription of 1800 mg/day in three doses of NAC or placebo. RESULTS: Dyspnea,
      cough, sputum, and wake-up dyspnea improved after 4 months of NAC compared to the
      control group. After 4 months, spirometric components were significantly improved
      in NAC group compared to placebo group. CONCLUSION: Fourth months administration
      of NAC (1800 mg daily) can improve clinical conditions and spirometric findings
      in mustard exposed in BOS class 1 or 2.

PMID- 18036808
TI  - Discussion of "effect of inoculation in composting processes: modifications in
      lignocellulosic fraction" Waste Management 27 (2007) 1099-1107.

PMID- 18036809
TI  - Label-free quantitative DNA detection using the liquid core optical ring
      resonator.
AB  - We demonstrated quantitative real-time label-free detection of DNA sequences
      using the liquid core optical ring resonator (LCORR) sensor. The LCORR is a
      recently developed sensing platform that integrates microfluidics and photonic
      sensing technology with low detection limit and sub-nanoliter detection volume.
      We analyzed experimentally and theoretically the LCORR response to a variety of
      DNA samples that had different strand lengths (25-100 bases), number of base-
      mismatches (1-5), and concentrations (10 pM to 10 microM) to evaluate the LCORR
      sequence detection capability. In particular, we established the linear
      correlation between the LCORR sensing signal and the molecule density, which
      allows us to accurately calculate the molecule density on the surface. It is
      found that the probe surface coverage was 26-51% and the extent of hybridization
      was 40-50%. The titration curve for 25-base probe and 25-base target DNA yields a
      dissociation constant of 2.9 nM. With a 37.1 nm/RIU LCORR, detection of 10 pM
      bulk DNA concentration was demonstrated. The mass detection limit was estimated
      to be 4 pg/mm(2), corresponding to a density of 10(10) molecules/cm(2) on the
      surface. We also showed that the LCORR was sensitive enough to differentiate DNA
      with only a few base-mismatches based on the raw sensing signal and kinetic
      analysis. Our work will provide important insight into the light-DNA interaction
      at the ring resonator surface and lay a foundation for future LCORR-based DNA
      label-free microarray development.

PMID- 18036810
TI  - Visualizing circuits and systems using transgenic reporters of neural activity.
AB  - Genetically encoded sensors of neural activity enable visualization of circuit
      level function in the central nervous system. Although our understanding of the
      molecular events that regulate neuronal firing, synaptic function, and plasticity
      has expanded rapidly over the past 15 years, an appreciation for how cellular
      changes are functionally integrated at the circuit level has lagged. A new
      generation of tools that employ fluorescent sensors of neural activity promises
      unique opportunities to bridge the gap between cellular level and system level
      analysis. This review will focus on genetically encoded sensors. A primary
      advantage of these indicators is that they can be nonselectively introduced to
      large populations of cells using either transgenic-mediated or viral-mediated
      approaches. This ability removes the nontrivial obstacles of how to get chemical
      indicators into cells of interest, a problem that has dogged investigators who
      have been interested in mapping neural function in the intact CNS. Five different
      types of approaches and their relative utility will be reviewed here: first,
      reporters of immediate-early gene (IEG) activation using promoters such as c-fos
      and arc; second, voltage-based sensors, such as GFP-coupled Na+ and K+ channels;
      third, Cl*-based sensors; fourth, Ca2+-based sensors, such as Camgaroo and the
      troponin-based TN-L15; and fifth, pH-based sensors, which have been particularly
      useful for examining synaptic activity of highly convergent afferents in sensory
      systems in vivo. Particular attention will be paid to reporters of IEG
      expression, because these tools employ the built-in threshold function that
      occurs with activation of gene expression, provoking new experimental questions
      by expanding the timescale of analysis for circuit-level and system-level
      functional mapping.

PMID- 18036812
TI  - Adipogenic, osteogenic and myofibrogenic differentiations of a rat malignant
      fibrous histiocytoma (MFH)-derived cell line, and a relationship of MFH cells
      with embryonal mesenchymal, perivascular and bone marrow stem cells.
AB  - Malignant fibrous histiocytoma (MFH) is regarded as an undifferentiated
      pleomorphic sarcoma with unproven histogenesis. We investigated pathobiological
      characteristics of a rat MFH cell line (MT-9). Immunocytochemically, MT-9 cells
      and MT-9-induced tumours reacted to vimentin, A3 (rat MFH cell-specific
      antibody), macrophage markers and alpha-SMA (myofibroblastic marker), indicating
      that MT-9 showed both histiocytic and (myo)fibroblastic features. Adipogenic
      supplement-added MT-9 showed increased accumulation of lipid droplets. Addition
      of BMP-2 or osteogenic supplement to MT-9 enhanced osteoblastic markers (ALP
      activity, osteocalcin mRNA expression and calcification). TGF-beta1-treated MT-9
      revealed increased numbers of alpha-SMA-immunopositive cells, and enhanced
      protein levels of alpha-SMA and fibronectin, indicating myofibrogenesis. In rat
      tissues, A3 labelled with immature mesenchymal and perivascular cells in foetuses
      and neonates, and with marrow stem cells in adults. c-kit mRNA expression was
      seen in bone marrows and MT-9. Collectively, progenitors of MFH should be sought
      in lineage of marrow stem cells capable of differentiating into mesenchymal
      cells.

PMID- 18036813
TI  - Protective stoma in anterior resection of the rectum: when, how and why?
AB  - BACKGROUND: The use of protective stoma in anterior resection (AR) is
      controversial. Neoadjuvant therapy, TME and laparoscopy seem to increase the rate
      of anastomotic dehiscences (a.d.). PATIENTS AND METHODS: In a prospective study,
      219 patients were submitted to elective open AR (109 patients), open AR+TME nerve
      sparing (110 patients), 35 of which had intrasphinteric anastomosis. Fifty-five
      patients were treated by neoadjuvant therapy. Primary stoma was not performed.
      RESULTS: We had 15 (6.8%) a.d.: 5 (2.3%) major and 10 (4.4%) minor. In the five
      major a.d. an immediate colostomy was performed with one death. In the 10 minor
      the a.d. was cured conservatively. CONCLUSIONS: A protective stoma is necessary
      in less than 10% of the patients treated with AR, so avoiding further surgery,
      mortality, morbidity and higher medical costs in most patients.

PMID- 18036814
TI  - Assessing the agronomic and environmental effects of the application of cattle
      manure compost on soil by multivariate methods.
AB  - Multivariate analysis was used for interpreting data from a pot experiment using
      samples of three Spanish soils. Samples of soil fertilized with compost were
      compared with untreated control samples. We also compared the effect of adding
      the compost to soil with a controlled moisture content of 50% of its water
      holding capacity (WHC), and to a near-saturated soil (95% WHC). Hierarchical
      cluster analysis (HCA) and principal component analysis (PCA) were used; they
      perfectly differentiated sample groups both as a function of the treatment
      applied and by sampling date. The compost samples were characterized by higher
      pH, electrical conductivity (EC), organic matter (OM) content and cation exchange
      capacity (CEC), together with nutrient concentrations than the control pots. The
      pots with a soil-compost mixture at 95% WHC presented lower values of EC, CEC,
      inorganic N, K, Na and B than the mixtures at 50% WHC. Multivariate methods may
      therefore be useful for the analysis and interpretation of a large number of data
      in soil research.

PMID- 18036815
TI  - Biodegradation of waste-lubricating petroleum oil in a tropical alfisol as
      mediated by animal droppings.
AB  - This study evaluated the applicability of some organic wastes from animal
      droppings as bioremediation alternative for soils spiked with waste-lubricating
      oil (spent oil). The total hydrocarbon contents (THC) with time of sampling were
      markedly reduced with addition of cow dung (CD), poultry manure (PM) and pig
      wastes (PW). The general trend in the first year indicated that PW stimulated the
      highest net percentage loss in THC for soils polluted with 5,000 mg kg(-1)
      (0.5%SP) and 50,000 mg kg(-1) (5%SP) oil levels. Poultry manure induced the
      highest reduction in soils polluted with medium, i.e. 2.5%SP (25,000 mg kg(-1))
      oil concentration. The overall net loss mediated by each organic waste in the 2nd
      year showed that PM addition was better irrespective of total oil loading. For
      example, at 3 months PM led to 16.1% and 14.6% net reduction in THC for soils
      treated with 50,000 mg kg(-1) (5%) and 100,000 mg kg(-1) (10%) total oil loading,
      respectively; whereas at same period, the performance of the organic wastes were
      relatively similar in soils with 10,000 mg kg(-1) oil loading. At 6 and 12
      months, PM reduced the oil levels better than CD and PW. Further evaluation by
      first-order kinetic model which utilized combine data for the entire periods for
      each year indicated that PW was better at low oil pollution level, while PM
      performed better at high oil pollution levels. Overall, the differential
      performance of these organic amendments followed PM>PW>CD.

PMID- 18036816
TI  - Waste treatment and biogas quality in small-scale agricultural digesters.
AB  - Seven low-cost digesters in Costa Rica were studied to determine the potential of
      these systems to treat animal wastewater and produce renewable energy. The
      effluent water has a significantly lower oxygen demand (COD decreased from 2,968
      mg/L to 472 mg/L) and higher dissolved nutrient concentration (NH(4)-N increased
      by 78.3% to 82.2mg/L) than the influent water, which increases the usefulness of
      the effluent as an organic fertilizer and decreases its organic loading on
      surface waters. On average, methane constituted 66% of the produced biogas, which
      is consistent with industrial digesters. Through principle component analysis,
      COD, turbidity, NH(4)-N, TKN, and pH were determined to be the most useful
      parameters to characterize wastewater. The results suggest that the systems have
      the ability to withstand fluctuations in the influent water quality. This study
      revealed that small-scale agricultural digesters can produce methane at
      concentrations useful for cooking, while improving the quality of the livestock
      wastewater.

PMID- 18036817
TI  - Synthesis and evaluation of novel chromogenic peptidase substrates based on 9-(4'
      aminophenyl)-10-methylacridinium salts as diagnostic tools in clinical
      bacteriology.
AB  - The synthesis and initial evaluation of novel chromogenic substrates with
      potential in the detection and differentiation of cultured bacterial colonies are
      described. The substrates were readily hydrolysed by specific aminopeptidase
      activity to release the chromogen, 9-(4'-aminophenyl)-10-methylacridinium salt,
      which provided a clear visual indication of the presence of the corresponding
      bacteria.

PMID- 18036818
TI  - Design and identification of selective HER-2 sheddase inhibitors via P1'
      manipulation and unconventional P2' perturbations to induce a molecular
      metamorphosis.
AB  - In an effort to obtain a MMP selective and potent inhibitor of HER-2 sheddase
      (ADAM-10), the P1' group of a novel class of (6S,7S)-7-[(hydroxyamino)carbonyl]-6
      carboxamide-5-azaspiro[2.5]octane-5-carboxylates was attenuated and the structure
      activity relationships (SAR) will be discussed. In addition, it was discovered
      that unconventional perturbation of the P2' moiety could confer MMP selectivity,
      which was hypothesized to be a manifestation of the P2' group effecting global
      conformational changes.

PMID- 18036819
TI  - Multiagent chemotherapy studied in a xenograft model of medulloblastoma/primitive
      neuroectodermal tumour: analysis of the VETOPEC regimen.
AB  - Brain tumours remain the most important challenge in the treatment of childhood
      cancer. The intraocular (io) xenograft model was used to study components and
      variations of the VETOPEC multiagent chemotherapy regimen in the
      medulloblastoma/primitive neuroectodermal tumour (MB/PNET) xenograft cell line
      JRMB-6. VETOPEC, a combination of vincristine (VCR), etoposide (VP-16) and
      escalated dose cyclophosphamide (CPA), has been shown to be highly active in
      clinical trials. A total of 190 xenografted tumours were treated with one of nine
      regimens: saline; single agent CPA, VP-16 (single dose [sd], five dosages daily
      [dx5] or continuous infusion, [ci]) or VCR; combinations of CPA (dx5)+VP-16 (dx5
      or ci) or CPA (dx5)+VP-16 (ci)+VCR (sd). Results were calculated using both
      response (volume reduction >50%) and 'time to progression' (TtP). Effectiveness
      of CPA was confirmed. Single-agent VCR or VP-16 produced no response. No
      difference was documented in TtP with VCR, VP-16 (sd) or VP-16 (dx5) versus
      control, but a significant prolongation occurred when VP-16 was given by ci
      (p=0.001). With the 3-agent combination of CPA+VP-16 (ci)+VCR a significantly
      prolonged TtP was documented versus both single agent CPA (p=0.003) and the
      combination of CPA+VP-16 (dx5) (p=0.004). The results suggest improved efficacy
      of VP-16 when given as ci in both single-agent and combination settings. The
      addition of VP-16 (ci)+VCR to an already effective dosage of CPA further prolongs
      TtP. These data support and progress VETOPEC phase II clinical studies and
      suggest potential further benefits of prolonged exposure to VP-16 by ci.

PMID- 18036820
TI  - A novel sesquiterpenoid dimer parviflorene F induces apoptosis by up-regulating
      the expression of TRAIL-R2 and a caspase-dependent mechanism.
AB  - Parviflorene F (1), a novel sesquiterpenoid dimer isolated from Curcuma
      parviflora Wall, is a cytotoxic compound. In this study, we examined the
      mechanism of its cytotoxic effect in HeLa cells. Treatment with 1 enhanced the
      mRNA and protein expression of TRAIL-R2 (tumor necrosis factor alpha-related
      apoptosis inducing ligand receptor 2). Apoptosis was induced by 1 as revealed by
      the distribution of DNA and Annexin V/PI staining using flow cytometry. In
      addition, 1-induced apoptosis was inhibited by human recombinant TRAIL-R2/Fc
      chimera protein, TRAIL-neutralizing fusion protein. Also, we found that 1 induced
      the activation of caspase-8, caspase-9, and caspase-3, indicating that the
      cytotoxic effect of 1 is correlated with apoptosis by a caspase-dependent
      mechanism through TRAIL-R2. In addition, 1 enhanced TRAIL-induced cell death
      against HeLa and TRAIL-resistant DLD1 cells. Taken together, up-regulation of
      TRAIL-R2 by 1 may contribute to sensitization of TRAIL-induced cell death.

PMID- 18036821
TI  - Virtual screening approaches for the identification of non-lipid autotaxin
      inhibitors.
AB  - Autotaxin (ATX, NPP-2) catalyzes the conversion of lysophosphatidyl choline (LPC)
      to lysophosphatidic acid (LPA), a mitogenic cell survival factor that stimulates
      cell motility. The high expression of both ATX and receptors for LPA in numerous
      tumor cell types has produced substantial interest in exploring ATX as an
      anticancer chemotherapeutic target. ATX inhibitors reported to date are analogs
      of LPA, a phospholipid, and are more hydrophobic than is typical of orally
      bioavailable drugs. This study applied both structure-based and ligand-based
      virtual screening techniques with hit rates of 20% and 37%, respectively, to
      identify a promising set of non-lipid, drug-like ATX inhibitors. Structure-based
      virtual screening necessitated development of a homology model of the ATX
      catalytic domain due to the lack of structural information on any mammalian NPP
      family member. This model provided insight into the interactions necessary for
      ATX inhibition, and produced a suitably diverse training set for the development
      and application of binary QSAR models for virtual screening. The most efficacious
      compound identified in this study was able to completely inhibit ATX-catalyzed
      hydrolysis of 1 microM FS-3 (a synthetic, fluorescent LPC analog) at a 10 microM
      concentration.

PMID- 18036823
TI  - Investigation of the oxide shell forming on epsilon-Co nanocrystals.
AB  - This paper reports on the TEM characterization of the surface oxide layer forming
      on Co nanocrystals (NCs) prepared using a standard method [Puntes, V.F.,
      Krishnan, K.M., Alivisatos, P., 2001. Synthesis, self-assembly, and magnetic
      behavior of a two-dimensional superlattice of single-crystal epsilon-Co
      nanoparticles. Appl. Phys. Lett. 78 (15), 2187-2189]. Complementary transmission
      electron microscopy (TEM)-related techniques presented direct evidence of a 1.5
      3nm CoO shell forming on epsilon-Co NCs. The crystalline structure of the Co NCs
      was confirmed by selected area diffraction study while the nature of the shell
      was probed by energy-loss near-edge spectroscopy and energy-filtered TEM. Based
      on these results, we comment on the detection of nanoscale feature with energy
      filtered imaging.

PMID- 18036822
TI  - Synthesis, characterization and antiproliferative studies of the enantiomers of
      cis-[(1,2-camphordiamine)dichloro]platinum(II) complexes.
AB  - The platinum(II) complex cis-[(1S,2R,3S)-1,7,7-trimethylbicyclo[2.2.1]heptane-2,3
      diamine]dichloroplatinum(II) (1) and its enantiomer (2) have been synthesized and
      physically and spectroscopically characterized. To obtain the enantiopure
      complexes the chiral pool approach was applied. The synthetic pathway has four
      steps, starting from (+/-)-diphenylethylenediamine (DPEDA) (3) and the natural
      products (1S)-camphorquinone or (1R)-camphorquinone to obtain enantiomers 1 and
      2, respectively. The interaction of the Pt(II) complexes with DNA was studied by
      several techniques: circular dichroism, electrophoresis on agarose gel and atomic
      force microscopy (AFM). These studies showed differences in the degree of
      interaction between both enantiomers and DNA (calf thymus DNA and plasmid pBR322
      DNA). The cytotoxicity of enantiomers 1 and 2 against the HL-60 cell line was
      studied by in vitro tests of antiproliferative activity, incubating during both
      24 h and 72 h. An important difference of activity was found between both
      enantiomers regarding the IC50 data at 24 h of incubation. Thus, complex 1 showed
      to be much more active than its enantiomer 2.

PMID- 18036824
TI  - Fourier-ratio deconvolution and its Bayesian equivalent.
AB  - We discuss how an inner-shell electron energy-loss spectrum can be processed
      using Bayesian (maximum-entropy or maximum-likelihood) deconvolution to
      simultaneously remove plural scattering and improve the energy resolution. As in
      Fourier-ratio deconvolution, a low-loss spectrum (recorded from the same area of
      specimen) is used as a kernel or resolution function. This procedure avoids the
      need to record the zero-loss peak in the absence of a specimen and uncertainties
      related to the width of the zero-loss peak. Unlike the case of Fourier-ratio
      deconvolution, we find that core-loss data do not require pre-edge background
      subtraction and extrapolation towards zero intensity; simply matching the
      intensity at both ends of the region is usually sufficient to avoid oscillatory
      artifacts. Using the low-loss spectrum as both data and kernel yields a zero-loss
      peak whose width provides an indication of the energy resolution as a function of
      the number of iterations. Finally, we argue that Fourier-ratio deconvolution or
      its Bayesian equivalent is the correct way to remove the substrate or matrix
      contribution to an energy-loss spectrum recorded from a particle on a substrate
      or embedded in a matrix.

PMID- 18036825
TI  - Electron energy loss near edge structure (ELNES) spectra of AlN and AlGaN: a
      theoretical study using the Wien2k and Telnes programs.
AB  - Several aspects of the modelling of the energy loss near edge structure (ELNES)
      using the Wien2k code and the Telnes program are discussed in this paper. A case
      study with ground state, partial and full core-hole calculations of wurtzite AlN
      was performed and the results were compared with experimental transmission
      electron microscopy data. The best agreement with the experimental observations
      was obtained for the full core-hole case. Changes in the ELNES spectra for
      various core-hole charges are explained by investigating the site and symmetry
      projected density of states. Directionally resolved N K-edge ELNES of AlN are
      discussed and the magic angle beta approximately 2.5mrad is identified which is
      in a good agreement with other theoretical predictions. Finally, preliminary
      results on a compositional study of Al(x)Ga(1-x)N are explored.

PMID- 18036826
TI  - 99m Tc-glycopeptide: synthesis, biodistribution and imaging in breast tumor
      bearing rodents.
AB  - This study was aimed to develop a glycopeptide (GP) to be used as a carrier for
      anti-cancer drug delivery. GP was synthesized by conjugating glutamate peptide
      and chitosan using carbodiimide as a coupling agent. Elemental analysis and
      capillary electrophoresis confirmed the purity was >95%. GP was labeled with
      sodium pertechnetate (Na99m TcO4) for in vitro and in vivo studies. Rhenium-GP
      was synthesized to support the binding site of 99m Tc at the glutamate positions
      3-5. In vitro cellular uptake of 99m Tc-GP was performed in breast cancer cells.
      Cytosol had 60% whereas nucleus had 40% uptake of 99m Tc-GP. When cancer cells
      were incubated with glutamate or aspartate, followed by 99m Tc-GP, there was
      decreased uptake in cells treated with glutamate but not aspartate. The findings
      indicated that cellular uptake of 99m Tc-GP was via glutamate transporters. In
      addition, 99m Tc-GP was able to measure uptake differences after cells treated
      with paclitaxel. Biodistribution and planar imaging were conducted in breast
      tumor-bearing rats. Biodistribution of 99m Tc-GP showed increased tumor-to-tissue
      ratios as a function of time. Planar images confirmed that 99m Tc-GP could assess
      tumor uptake changes after paclitaxel treatment. In vitro and in vivo studies
      indicated that GP could target tumor cells, thus, GP may be a useful carrier for
      anti-cancer drug delivery.

PMID- 18036827
TI  - Inhibition of multidrug resistance transporters in the diatom Thalassiosira
      rotula facilitates dye staining.
AB  - Cells are protected by multidrug resistance transporters, which remove
      potentially harmful chemicals entering the cells from the environment or
      originating endogenously from the cellular metabolism. Multidrug resistance
      transporters have not been investigated so far in marine eukaryotic algae like
      diatoms. We investigated the uptake of a calcium-sensitive dye, Fura 2
      acetoxymethylester (AM), by the marine diatom Thalassiosira rotula in the
      presence and absence of substances known to inhibit multidrug resistance
      transporters (ATP-binding cassette transporters, ABC). Three inhibitors known to
      block transporters in living organisms were tested in the marine diatom T.
      rotula. We applied verapamil, which blocks multidrug resistance P-glycoprotein
      (MDR1), probenecid as an inhibitor of organic anion transport and the specific
      inhibitor of multidrug resistance-associated protein (MRP), MK571, obtaining
      positive results with the highly specific MK571. This leads to the assumption
      that the cells of T. rotula possess MRP transporters. Marine diatom cells can now
      be loaded by incubation with a calcium-sensitive dye, which facilitates
      measurements of cellular calcium signals without using methods risking injury of
      the cell membrane. This opens an avenue for investigation on diatom calcium
      signalling and perhaps how they process environmental signals.

PMID- 18036828
TI  - Biventricular repair in children with complete atrioventricular septal defect and
      a small left ventricle.
AB  - OBJECTIVE: Biventricular repair of complete atrioventricular septal defect
      (CAVSD) with small left ventricle aims to restore the normal loading conditions
      of the left ventricle. This report retrospectively evaluates the outcome of
      biventricular repair in 19 children with CAVSD and a small left ventricle.
      METHODS: Our computer database was searched for all patients with CAVSD operated
      on between January 1988 and December 2005. Patients who underwent biventricular
      repair of CAVSD were considered for investigation if they had a preoperative left
      ventricle-to-right ventricle long axis ratio (LAR) of <1.1 as determined by
      cardiac catheterization. RESULTS: There were 259 patients who underwent surgical
      correction of complete atrioventricular septal defect. Nineteen (10.3%) of 184
      patients who underwent biventricular repair had small left ventricle based on LAR
      measurements. These children had no other associated congenital heart anomalies
      and had no previous surgery. Nine of these children had associated Trisomy 21.
      There were 10 (52.6%) males and 9 (47.4%) females, with age of 1-210 (122+/-67)
      days and weight of 2.5-9.0 (5.26+/-1.7) kg at surgery. Mean LAR was 0.76+/-0.14.
      Two patients (10.5%) died on the 8th and 11th postoperative day, respectively.
      Both had very small left ventricle (LAR of 0.45 and 0.60, respectively) and
      received ECMO support for postoperative low output syndrome and intractable
      pulmonary hypertension. A patient with an LAR of 0.62 who had ECMO support for
      postoperative myocardial failure underwent successful heart transplantation on
      the 21st postoperative day. The long-term survivors (89.5%) with LAR>0.65 had an
      uncomplicated postoperative course, had undergone regular follow-up (65+/-36
      months) with echocardiographic assessment of the left ventricle, and had good
      left ventricular function. There was no early reoperation for residual
      ventricular septal defect, left AV valve regurgitation, or left ventricular
      outflow tract obstruction. Late reoperation was performed in three patients
      (17.4%) who underwent mitral valve repair for significant regurgitation in the
      18th, 59th, and 87th month postoperatively. CONCLUSIONS: Biventricular repair of
      CAVSD with small left ventricle in infants and children whose LAR is >0.65,
      although not without risks, improve patients' functional and clinical status even
      in long-term follow-up. Particular caution should be taken in patients with LAR
      of <0.65, since these are patients who may not be amenable to biventricular
      repair, but for whom univentricular palliation may be more suitable.

PMID- 18036829
TI  - The differential effect of Eriobotrya japonica hydrophilic leaf extract on
      cytokines production and modulation.
AB  - Stimulating or modulating the release of cytokines by immunomodulators or
      immunostimulating agents is an attractive mode for treating several diseases such
      as viral infections. For instance, patients with viral infections may be in need
      of increasing or inducing T helper 1 (Th1) or proinflammatory cytokines, which
      ultimately activate T cytotoxic and Natural killer lymphocytes to kill virally
      infected cells. Of these agents, we found that Eriobotrya japonica hydrophilic
      leaf extract (EJHE) can induce and modulate cytokines in dose-dependent manner.
      Twenty-four hour exposure of increasing concentrations of EJHE increased
      significantly (p<0.001) the production of IFN-gamma and TNF-alpha, from PHA+LPS
      stimulated whole blood. However, the production of IFN-gamma and TNF-alpha
      plateaued at high EJHE concentrations (10-100 microg/ml). No significant changes
      in the production of IL-10 were seen. In addition, EJHE at 1 and 10 microg/ml
      reversed significantly (p < 0.01) the inhibitory effect of hydrocortisone on the
      IL-12 p70, IFN-gamma and TNF-alpha production from PHAS+LPS stimulated whole
      blood. Without PHA and LPS, EJHE was found to induce significantly (p<0.001) IFN
      gamma, IL-12 p70, TNF-alpha, and IL-10 from whole blood culture in concentration
      dependent manner. The maximum induction of IFN-gamma, IL-12 p70, and TNF-alpha by
      EJHE was at 1 and 10 microg/ml. On the other hand, IL-10 induction kept
      increasing even at the highest concentration used (100 microg/ml) of EJHE.
      Furthermore, intra-peritoneal injection of EJHE into mice increased significantly
      serum cytokines level mainly at 10 and 100 microg/ml. Two-hour post i.p.
      injection, EJHE increased serum IFN-gamma, TNF-alpha, and IL-10 to approximately
      750, 1000, and 250 pg/ml, respectively. However, 24h post i.p. injection, the
      levels of TNF-alpha, and IL-10 were similar to basal levels but IFN-gamma levels
      were 200 pg/ml. These results indicate that EJHE induces proinflammatory and Th1
      cytokines in concentration dependent manner and the effect of this induction
      should be studied further in viral models to check the efficacy of such cytokine
      induction.

PMID- 18036830
TI  - Comparison of protein quantification and extraction methods suitable for E. coli
      cultures.
AB  - Many different extraction and analysis methods exist to determine the protein
      fraction of microbial cells. For metabolic engineering purposes it is important
      to have precise and accurate measurements. Therefore six different protein
      extraction protocols and seven protein quantification methods were tested and
      compared. Comparison was based on the reliability of the methods and boxplots of
      the normalized residuals. Some extraction techniques (SDS/chloroform and toluene)
      should never be used: the measurements are neither precise nor accurate.
      Bugbuster extraction combined with UV280 quantification gives the best results,
      followed by the combinations Sonication-UV280 and EasyLyse-UV280. However, if one
      does not want to use the quantification method UV280, one can opt to use
      Bugbuster, EasyLyse or sonication extraction combined with any quantification
      method with exception of the EasyLyse-BCA_P and Sonication-BCA_P combinations.

PMID- 18036831
TI  - The effect of peptide glycation on local secondary structure.
AB  - Protein glycation is a non-enzymatic reaction between reducing sugars and amino
      groups that occurs in vivo and has been implicated in a number of disease states
      and pathologies including Alzheimer's and diabetes. Although glycation is thought
      to alter protein structure and function, there is currently little information on
      the structural consequences of this modification. We have used a model alpha
      helix and a model beta-hairpin peptide, and NMR analysis, to investigate the
      effects of glycation upon secondary structure. Glycation of the dilysine motif
      within the alpha-helix peptide occurred preferentially at one lysine residue and
      resulted in severe disruption to the local secondary structure. The area
      immediately around the site of modification was extremely flexible and the
      peptide did not adopt a preferred conformation in this area of the helix in 30%
      TFE. Significant glycation of the beta-hairpin peptide was not detected and the
      structure was unchanged. These results show that glycation results in local
      secondary structure distortion of alpha-helices and that preferential glycation
      occurs in a sequence specific manner. The findings will allow us to interrogate
      the local environment in other peptides/proteins to predict the likelihood of
      glycation, and to model the potential effects such modification might have upon
      structure/function.

PMID- 18036832
TI  - Motor unit synchronization during fatigue: a novel quantification method.
AB  - Motor unit (MU) synchronization is the result of commonality in the pre-synaptic
      input to MUs. Previously proposed techniques to estimate MU synchronization based
      on invasive and surface electromyography (sEMG) recordings have been,
      respectively, limited by the analyzed MU population size and influence of changes
      in muscle fibre conduction velocities (MFCVs). The aim of this paper was to
      evaluate a novel descriptor of MU synchronization on a large MU population, and
      to minimize its dependency on MFCV. The method is based on the asymmetry of MU
      action potentials, causing synchronized MU action potentials to skew the
      monopolar sEMG signal distribution. The descriptor was the skewness statistic
      used on sub-band filtered monopolar sEMG signals (sub-band skewness). The method
      was evaluated using simulated signals and its performance was evaluated in terms
      of bias and sensitivity of the sub-band skewness quantifying the MU
      synchronization level. The best sensitivity was obtained using sub-band filtering
      at scale 5 (Mexican hat wavelet). The sensitivity was in general about 0.1units
      per 5% MU synchronization level. Changes in MFCV had a minimal influence, and
      caused at most a 5% deviant MU synchronization quantification level. A halved
      recruitment level had higher bias and a 20% lower sensitivity. Increased firing
      rate (14-34Hz) reduced the sensitivity about 50%. The sensitivity of the
      descriptor was robust to noise, and different volume conduction properties. It
      should be noted that the sub-band skewness comprises a subject-dependent
      component implying that only changes in MU synchronization level can be
      quantified.

PMID- 18036833
TI  - fMRI-EEG integrated cortical source imaging by use of time-variant spatial
      constraints.
AB  - In response to the need of establishing a high-resolution spatiotemporal
      neuroimaging technique, tremendous efforts have been focused on developing
      multimodal strategies that combine the complementary advantages of high-spatial
      resolution functional magnetic resonance imaging (fMRI) and high-temporal
      resolution electroencephalography (EEG) or magnetoencephalography (MEG). A
      critical challenge to the fMRI-EEG/MEG integration lies in the spatial mismatches
      between fMRI activations and instantaneous electrical source activities. Such
      mismatches are fundamentally due to the fact that fMRI and EEG/MEG signals are
      generated and collected in highly different time scales. In this paper, we
      propose a new theoretical framework to solve the problem of fMRI-EEG integrated
      cortical source imaging. The new framework has two principal technical
      advancements. First, by assuming a linear neurovascular coupling, a method is
      derived to quantify the fMRI signal in each voxel as proportional to the time
      integral of the power of local electrical current during the period of event
      related potentials (ERP). Second, the EEG inverse problem is solved for every
      time instant using an adaptive Wiener filter, in which the prior time-variant
      source covariance matrix is estimated by combining the quantified fMRI responses
      and the segmented EEG signals before response averaging. A series of computer
      simulations were conducted to evaluate the proposed methods in terms of imaging
      the instantaneous cortical current density (CCD) distribution and estimating the
      source time courses with a millisecond temporal resolution. As shown in the
      simulation results, the instantaneous CCD reconstruction by using the proposed
      fMRI-EEG integration method was robust against both fMRI false positives and
      false negatives while retaining a spatial resolution nearly as high as that of
      fMRI. The proposed method could also reliably estimate the source waveforms when
      multiple sources were temporally correlated or uncorrelated, or were sustained or
      transient, or had some features in frequency or phase, or had even more
      complicated temporal dynamics. Moreover, applying the proposed method to real
      fMRI and EEG data acquired in a visual experiment yielded a time series of
      reconstructed CCD images, in agreement with the traditional view of hierarchical
      visual processing. In conclusion, the proposed method provides a reliable
      technique for the fMRI-EEG integration and represents a significant advancement
      over the conventional fMRI-weighted EEG (or MEG) source imaging techniques and is
      also applicable to the fMRI-MEG integrated source imaging.

PMID- 18036834
TI  - An investigation of statistical power for continuous arterial spin labeling
      imaging at 1.5 T.
AB  - Variance estimates can be used in conjunction with scientifically meaningful
      effect sizes to design experiments with type II error control. Here we present
      estimates of intra- and inter-subject variances for region of interest (ROI) from
      resting cerebral blood flow (CBF) maps obtained using whole brain, spin echo
      echoplanar (SE-EPI) continuous arterial spin labeling (CASL) imaging on 52
      elderly subjects (age=70.5+/-7.9 years, 29 males). There was substantial
      intrasubject systematic variability in CBF of gray matter ROIs corresponding to a
      range of standard deviations=[39-168] (ml/(100 g min)). This variability was
      mainly due to two factors: (1) an expected inverse relationship between ROI
      volume and intrasubject variance and (2) an increased effective post-labeling
      delay for more superior slices acquired later in the sequence. For example,
      intrasubject variance in Brodmann area 4 (BA 4) was approximately 8 times larger
      than in hippocampus, despite their similar gray matter volumes. Estimated ROI
      wise power was computed for various numbers of acquired CBF images, numbers of
      subjects, and CBF effect sizes for two experimental designs: independent sample t
      test and paired t-test. The theoretical effects of pulse sequence and field
      strength on general applicability of these results are discussed.

PMID- 18036835
TI  - Sex differences in the serotonin 1A receptor and serotonin transporter binding in
      the human brain measured by PET.
AB  - Women and men differ in serotonin associated psychiatric conditions, such as
      depression, anxiety and suicide. Despite this, very few studies focus on sex
      differences in the serotonin system. Of the biomarkers in the serotonin system,
      serotonin(1A) (5-HT(1A)) receptor is implicated in depression, and anxiety and
      serotonin transporter (5-HTT) is a target for selective serotonin reuptake
      inhibitors, psychotropic drugs used in the treatment of these disorders. The
      objective of the present study was to study sex related differences in the 5
      HT(1A) receptor and 5-HTT binding potentials (BP(ND)s) in healthy humans, in
      vivo. Positron emission tomography and selective radioligands [(11)C]WAY100635
      and [(11)C]MADAM were used to evaluate binding potentials for 5-HT(1A) receptors
      (14 women and 14 men) and 5-HTT (8 women and 10 men). The binding potentials were
      estimated both on the level of anatomical regions and voxel wise, derived by the
      simplified reference tissue model and wavelet/Logan plot parametric image
      techniques respectively. Compared to men, women had significantly higher 5-HT(1A)
      receptor and lower 5-HTT binding potentials in a wide array of cortical and
      subcortical brain regions. In women, there was a positive correlation between 5
      HT(1A) receptor and 5-HTT binding potentials for the region of hippocampus. Sex
      differences in 5-HT(1A) receptor and 5-HTT BP(ND) may reflect biological
      distinctions in the serotonin system contributing to sex differences in the
      prevalence of psychiatric disorders such as depression and anxiety. The result of
      the present study may help in understanding sex differences in drug treatment
      responses to drugs affecting the serotonin system.

PMID- 18036836
TI  - Long-term outcome of anterior stabilization of the shoulder.
AB  - This study reports long-term experience with anterior shoulder capsule
      stabilization by performing the Bankart repair when labral tearing was present
      with a laterally based T-capsule repair in both primary and revision surgery.
      Between 1979 and 1983, 34 patients underwent this procedure. They were
      categorized into a primary group of 22 patients and a revision group of 12
      patients who had previous surgery to correct anterior shoulder instability.
      Patients completed our shoulder questionnaire and a Rowe questionnaire. The mean
      follow-up was 22 years (range, 11-27 years). No recurrent dislocations developed,
      4 patients reported shoulder subluxation, and 11 felt apprehension. No patient
      had further anterior instability surgery. Two received total shoulder
      arthroplasty. Postoperative average pain was 1.6, average strength was 9.0, and
      average satisfaction was 8.3 (1-10 scales). Active elevation averaged 169
      degrees, external rotation, 65 degrees; and internal rotation was to T12. There
      was an average of 10.2 "yes" responses on the Simple Shoulder Test. The total
      American Shoulder and Elbow Surgeons score averaged 84.3. Applying the Rowe
      rating, results were excellent in 16, good in 10, fair in 2, and poor in 4.
      Ratings were better in the primary surgery group (P = .0535). The use of this
      procedure for correction of shoulder instability can prevent recurrent
      dislocation, but some degree of instability remains. Clinically important
      arthritis seldom develops.

PMID- 18036837
TI  - Arthroscopy-assisted reduction of impression fracture of the humeral head: a case
      report.

PMID- 18036838
TI  - Complete bony union achieved after arthrodesis of native glenoid and acromion to
      an allograft proximal humerus: a case report.

PMID- 18036839
TI  - Shoulder kinematics in patients with full-thickness rotator cuff tears after a
      subacromial injection.
AB  - The purpose of this study was to test the hypothesis that scapulohumeral rhythm
      (SHR) is altered in patients with full-thickness rotator cuff tears due to pain.
      Fifteen subjects (mean age, 60.2 +/- 8.9 years; mean height, 1.72 +/- 0.10 m;
      mean weight, 85.43 +/- 18.32 kg) performed humeral elevation in the 3 planes
      before and after a lidocaine injection. Pain was assessed by use of a visual
      analog scale, and data were collected with an electromagnetic tracking system.
      Three-dimensional scapular kinematics (scapulothoracic motion) and glenohumeral
      elevation were assessed. A linear regression model was used to calculate SHR
      (ratio of scapulothoracic motion to glenohumeral elevation) for equal phases of
      elevation (I, II, and III) and lowering (IV, V, and VI). Pain was significantly
      reduced (P </= .05), causing shifts in SHR to occur for frontal plane elevation
      (phase III, 1:1.72 to 1:2.78; phase V, 1:1.56 to 1:2.56), resulting in an
      increase in glenohumeral motion and a reduced reliance on scapular rotation for
      humeral motion. As SHR decreased, the contribution of glenohumeral elevation
      increased significantly whereas scapular upward and downward rotation tended to
      decrease. Differences in anterior-posterior and medial-lateral tilting of the
      scapula did not correspond with changes in SHR. The findings provide evidence of
      compensatory increases in SHR due to pain associated with full-thickness rotator
      cuff tear.

PMID- 18036840
TI  - The coracoacromial ligament: the morphology and relation to rotator cuff
      pathology.
AB  - We dissected 80 shoulders from 44 fresh cadavers to define variants of the
      coracoacromial ligament and their relationship to rotator cuff degeneration. The
      shapes and the geometric data of the ligaments were investigated, and the rotator
      cuffs of the cadavers were evaluated macroscopically. Five main types of
      coracoacromial ligaments were found: Y-shaped, broad band, quadrangular, V
      shaped, and multiple-banded. The Y-shaped ligament was the most frequent type,
      with a frequency of 41.3%, and the V-shaped ligament (11.2%) has not been
      previously reported. Of the cadavers that were dissected bilaterally, 64% showed
      the same type of ligament. There was no statistical significance between rotator
      cuff degeneration and the type or geometric measurement of the ligament. However,
      the coracoacromial ligaments with more than 1 bundle showed significant
      association with rotator cuff degeneration with a longer lateral border and
      larger coracoid insertion.

PMID- 18036841
TI  - The relationship between greater tuberosity osteopenia and the chronicity of
      rotator cuff tears.
AB  - This study investigated whether a relationship exists between greater tuberosity
      osteopenia and chronicity of rotator cuff tears. In a retrospective study,
      anteroposterior radiographs of 28 shoulders in 27 patients who had undergone
      surgical repair for rotator cuff tears were reviewed. Greater tuberosity
      osteopenia scores were created using National Institutes of Health digital image
      software. There was no significant difference in the mean age between patients
      with minimal to mild rotator cuff tear retraction (63.1 +/- 6.14 years) and
      patients with moderate to severe rotator cuff tear retraction (63.4 +/- 9.76
      years; P = .77). Of the 13 patients with minimal to mild rotator cuff tear
      retraction, 10 (77%) were women and 3 (23%) were men. Of 14 patients (50%) with
      moderate to severe rotator cuff tear retraction, 7 were men and 7 were women. The
      mean greater tuberosity osteopenia score in the 15 patients with moderate to
      severe retraction (0.48 +/- 0.095) was significantly less than the greater
      tuberosity osteopenia score in the 13 patients with minimal to mild retraction
      (0.58 +/- 0.135; P < .05). Furthermore, the mean greater tuberosity osteopenia
      score in 6 patients with chronic retracted rotator cuff tears (0.48 +/- 0.125)
      was significantly less than in the 6 patients with acute minimally retracted
      tears (0.64 +/- 0.119, P < .05). There were significantly greater osteopenic
      changes in the greater tuberosity in patients with chronic retracted rotator cuff
      tears. The greater tuberosity osteopenia may affect anchor pullout strength and
      the healing biology that influences overall rotator cuff repair healing rates.

PMID- 18036842
TI  - Primary osteoarthritis of the elbow: lack of radiographic evidence for
      morphologic predisposition, results of operative debridement at intermediate
      follow-up, and basis for a new radiographic classification system.
AB  - This study evaluated whether or not a morphologic predisposition exists to the
      development of primary osteoarthritis and establishes a classification tool to
      predict outcome in surgical treatment of elbow osteoarthritis. Detailed
      radiographic morphologic analysis of the ulnotrochlear and radio-capitellar
      joints in 90 normal and 24 osteoarthritic elbows showed few differences. Based
      upon commonly demonstrated radiographic features of degenerative changes, joint
      space narrowing, and marginal osteophytes, a classification system for rating the
      severity of primary osteoarthritis of the elbow was developed and applied
      retrospectively classified the preoperative radiographs of 18 patients (21
      elbows) who had undergone elbow debridement and capsular release through a
      lateral collateral ligament preserving approach. Clinical and radiographic
      outcomes were assessed at an average 65 months postoperative. Total elbow motion
      and Mayo elbow performance scores were best in those who had been classified as
      class I preoperatively and worst in those in class III. This newly developed
      radiographic classification system is a useful tool in predicting surgical
      outcome following debridement of primary elbow osteoarthritis.

PMID- 18036843
TI  - Malformation of the humerus in a patient with Ollier disease treated with the
      Ilizarov technique.

PMID- 18036844
TI  - Poorer elbow proprioception in patients with lateral epicondylitis than in
      healthy controls: a cross-sectional study.
AB  - Two groups of women, 15 patients with lateral epicondylitis and 21 healthy
      controls, were studied to compare proprioception in the elbows and knees between
      the groups. Outcome measures were absolute error and variable error for joint
      position sense and for threshold to detection of a passive movement. Both
      absolute error and variable error of threshold to detection of a passive movement
      were greater in the lateral epicondylitis-diagnosed elbows than in the controls'
      elbows (lateral epicondylitis, 1.8 degrees vs controls 1.1 degrees, P = .026;
      lateral epicondylitis, 0.8 degrees vs controls 0.3 degrees, P = .015), and there
      was a tendency toward a greater absolute error of joint position sense compared
      with the control elbows (lateral epicondylitis, 8.2 degrees vs controls, 5.6
      degrees; P = .078). Absolute error of joint position sense was greater in the
      elbows than in the knees of the lateral epicondylitis patients, but no group
      differences were found for knees. Proprioception seems, therefore, to be poorer
      in elbows with lateral epicondylitis elbows than in the controls' elbows. This
      needs to be taken into consideration in the management of lateral epicondylitis.

PMID- 18036845
TI  - The fate of elbow arthrodesis: indications, techniques, and outcome in fourteen
      patients.
AB  - Arthrodesis of the elbow remains a salvage procedure. In elbow surgery, it is
      indicated in cases of painful loss of motion, instability, and infection due to
      various causes. The literature lacks comprehensive clinical series concerning
      indications, techniques, and, particularly, outcome in elbow arthrodesis. We
      retrospectively reviewed our results of elbow arthrodesis in 14 patients. At
      final follow-up, the chart data of all patients showed favorable results with
      solid union of the fused elbows, no pain in 8 patients, and moderate pain in 4.
      In those patients in whom clinical follow-up was possible, after an average 62
      months (4-132), noteworthy functional results were observed because of
      compensatory motion of adjacent joints. The authors outline decisive factors in
      the decision making process for patients with salvage elbows, as well as the
      techniques for elbow arthrodesis. Our indications, favorable results, and
      complications are discussed. A comprehensive review of literature highlights the
      technical steps necessary for successful elbow arthrodesis.

PMID- 18036846
TI  - Subacromial bursa block is an effective alternative to interscalene block for
      postoperative pain control after arthroscopic subacromial decompression: a
      randomized trial.
AB  - Subacromial decompression surgery is associated with significant postoperative
      pain. We compared interscalene block (ISB) with subacromial bursa block (SBB).
      Sixty consecutive patients with subacromial impingement syndrome, scheduled for
      arthroscopic subacromial decompression surgery, were randomized into 3 groups
      receiving ISB (n = 19), SBB (n = 19), or no block (n = 15 [controls]). Patients
      with rotator cuff tears were excluded (n = 7). The postoperative consumption of
      morphine, time to the first bolus of morphine, oral analgesia, pain, sickness,
      and sedation scores were recorded. The pain scores in the ISB and SBB groups were
      lower than those in the control group in the first 12 hours postoperatively. The
      control group consumed more morphine (mean, 32.3 mg) compared with the SBB group
      (mean, 21.21 mg) and ISB group (mean, 14.00 mg) (P < .001). The time to first
      bolus was earlier in the control group (mean, 42.1 minutes) compared with both
      the SBB (mean, 92.6 minutes) and ISB (mean, 119.0 minutes) groups (P < .001). The
      oral analgesic intake was less in the SBB and ISB groups than in the controls (P
      = .004). Although ISB remains the gold standard, SBB provides effective, safe,
      and easily administered postoperative analgesia in patients with an intact
      rotator cuff undergoing arthroscopic subacromial decompression.

PMID- 18036847
TI  - Polyethylene dissociation after reverse total shoulder arthroplasty: the use of
      diagnostic arthroscopy.

PMID- 18036848
TI  - Humeral head translation decreases with muscle loading.
AB  - This study was conducted to determine the effect of in vitro passive and active
      loading on humeral head translation during glenohumeral abduction. A shoulder
      simulator produced unconstrained active abduction of the humerus in 8 specimens.
      Loading of the supraspinatus, subscapularis, infraspinatus/teres minor, and
      anterior, middle, and posterior deltoid muscles was simulated by use of 4
      different sets of loading ratios. Significantly greater translations of the
      humeral head occurred both in 3 dimensions (P < .001) and in the sagittal plane
      (P < .005) during passive motion when compared with active motion from 30 degrees
      to 70 degrees of abduction. In the sagittal plane, passive abduction experienced
      a resultant translation of 3.8 +/- 1.0 mm whereas the active loading ratios
      averaged 2.3 +/- 1.0 mm. There were no significant differences in the
      translations that were produced by the 4 sets of muscle-loading ratios used to
      achieve active motions. This study emphasizes the importance of the musculature
      in maintaining normal ball-and-socket kinematics of the shoulder.

PMID- 18036849
TI  - Forearm rotation in healthy adults of all ages and both sexes.
AB  - Factors such as sex, age, or hand dominance are supposed to influence forearm
      rotation; however, available data are scarce. This study therefore analyzed range
      of active supination and pronation bilaterally in 752 healthy white adults (age
      range, 20-95 years) of both sexes. Range of supination was higher than pronation.
      Range of forearm rotation was comparable between both sides, but it was higher in
      women than in men and inversely correlated with age. In contrast with women,
      where range started to decrease during the fifth decade of life, onset was later
      in men (seventh decade). No influence was observed with respect to hand dominance
      or constitutional variations. Thus, the contralateral side serves for clinical
      comparison independent from age, sex, hand dominance, or constitutional
      variances. The fact that several patients with a major limitation of pronation
      considered themselves healthy, but only 1 patient with limited supination did so,
      indirectly underlines the importance of restoring deficits of supination rather
      than pronation.

PMID- 18036850
TI  - A comparison of the Constant and Oxford shoulder scores in patients with
      conservatively treated proximal humeral fractures.
AB  - The Oxford shoulder scores (OSS) and Constant scores were collected prospectively
      for 103 patients treated conservatively for proximal humeral fractures. The
      paired scores were analyzed by assessing the degree of correlation, the agreement
      between the scores, and their sensitivity to change. Linear regression analysis
      was also performed. The scores correlated well with a coefficient of .84 (P <
      .001), demonstrating a clear relationship between the scoring systems. There was
      good agreement between the scores and both were sensitive to change over time (P
      < .001). We have also produced a regression equation (R2 = .70, P < .001) to
      predict the Constant score from the OSS. This study documents and compares the
      behavior of two scoring systems commonly used in the assessment of patients with
      proximal humeral fractures. The OSS may be considered as an alternative for
      assessing longer term follow-up, as, being solely subjective, it is easier to
      administer and correlates well with the Constant score.

PMID- 18036851
TI  - Initial fixation and cyclic loading stability of knotless suture anchors for
      rotator cuff repair.
AB  - This study evaluated the resistance to gapping and the mode of failure for 2
      knotless suture anchor systems used for rotator cuff repair compared with the
      performance of a conventional titanium anchor system. Eight matched pairs of
      fresh-frozen humeri were dissected free of all soft tissues and scanned to
      measure bone mineral density (BMD). The suture anchor systems tested were the
      TwinFix 5.0 Titanium (Smith & Nephew, Andover, MA), Bioknotless RC (DePuy Mitek,
      Norwood, MA), and Magnum (Opus Medical, San Juan Capistrano, CA), and each was
      inserted into each humerus. Cyclic, tensile loading was applied through the
      suture loop for 5000 cycles, or until failure, by using a servohydraulic testing
      machine. Gapping distances, defined as increasing elongation of the
      bone/anchor/suture system, were continuously measured. Total cycles to failure
      and mechanism of failure were documented. Mean initial (first cycle) and final
      (last cycle) gapping distances were 3.81 mm and 5.36 mm for the TwinFix 5.0, 4.02
      mm and 5.34 mm for the Bioknotless RC, and 3.56 mm and 4.98 mm for the Magnum
      anchors. No significant difference was detected among mean gap openings (P >
      .05). However, the Bioknotless RC had more early failures (5) than the other 2
      implants (1 each), approaching significance (P = .07). Trials of the Bioknotless
      RC that did not fail early were found to have significantly less gap opening than
      the other 2 systems for both initial (1.89 mm vs 3.82 mm for the TwinFix 5.0 and
      3.56 mm for the Magnum) and final (2.00 mm vs 4.68 mm for the TwinFix 5.0 and
      4.24 mm for the Magnum) gap opening. BMD was a significant predictor of initial
      (P = .029) and final (P = .008) gap opening, whereas the site of anchor insertion
      was a significant predictor of final displacement. The Opus Magnum was comparable
      with a conventional suture anchor, but the Mitek Bioknotless RC showed a trend
      toward early failure. Biomechanical analysis of knotless suture anchor systems
      can demonstrate trends among implants in an experimental setting. Knowledge of
      these trends could influence implant selection.

PMID- 18036852
TI  - A method for internal fixation of unstable distal clavicle fractures: early
      observations using a new technique.
AB  - Unstable distal clavicle fractures often require open reduction and internal
      fixation. A variety of fixation methods have been used and are currently in use.
      None of the current fixation methods seem to be without problems. We present a
      new technique and early observations using a distal radius locking T-plate
      normally used for fixation of distal radius fractures.

PMID- 18036853
TI  - Regarding "Apoptosis in the supraspinatus tendon with stage II subacromial
      impingement".

PMID- 18036854
TI  - DCL-1 colocalizes with other components of the MSUD machinery and is required for
      silencing.
AB  - In Neurospora, a gene present in an abnormal number of copies is usually a red
      flag for mischief. One way to deal with these potential intruders is by
      destroying their transcripts. Widely known as RNA interference (RNAi), this
      mechanism depends on the "dicing" of a double-stranded RNA intermediate into
      small-interfering RNA, which in turn guide the degradation of mRNA from the
      target gene. Quelling is a vegetative silencing system in Neurospora that
      utilizes such a mechanism. Quelling depends on the redundant activity of two
      Dicer-like ribonucleases, DCL-1 and DCL-2. Here, we show that Meiotic Silencing
      by Unpaired DNA (MSUD), a mechanism that silences expression from unpaired DNA
      during meiosis, requires the dcl-1 (but not the dcl-2) gene for its function.
      This result suggests that MSUD operates in a similar manner to Quelling and other
      RNAi systems. DCL-1 colocalizes with SAD-1 (an RdRP), SAD-2, and SMS-2 (an
      Argonaute) in the perinuclear region.

PMID- 18036855
TI  - Genetics of avirulence genes in Blumeria graminis f.sp. hordei and physical
      mapping of AVR(a22) and AVR(a12).
AB  - Powdery mildew fungi are parasites that cause disease on a wide range of
      important crops. Plant resistance (R) genes, which induce host defences against
      powdery mildews, encode proteins that recognise avirulence (AVR) molecules from
      the parasite in a gene-for-gene manner. To gain insight into how virulence
      evolves in Blumeria graminis f.sp. hordei, associations between segregating AVR
      genes were established. As a prerequisite to the isolation of AVR genes, two loci
      were selected for further analysis. AVR(a22) is located in a tightly linked
      cluster comprising AVR(a10) and AVR(k1) as well as up to five other AVR genes.
      The ratio between physical and genetic distance in the cluster ranged between 0.7
      and 35 kB/cM. The AVR(a22) locus was delimited by the previously isolated gene
      AVR(a10) and two cleaved amplified polymorphic sequence (CAPS) markers, 19H12R
      and 74E9L. By contrast, AVR(a12) was not linked to other AVR genes in two
      crosses. Bulk segregant analysis of over 100,000 AFLP fragments yielded two
      markers, ETAMTG-285 and PAAMACT-473, mapping 10 and 2cM from AVR(a12),
      respectively, thus delimiting AVR(a12) on one side. All markers obtained for
      AVR(a12) mapped proximal to it, indicating that the gene is located at the end of
      a chromosome. Three more AVR(a10) paralogues were identified at the locus
      interspersed among genes for metabolic enzymes and abundant repetitive elements,
      especially those homologous to the CgT1 class of retrotransposons. The flanking
      and close markers obtained will facilitate the isolation of AVR(a22) and AVR(a12)
      and provide useful tools for studies of the evolution of powdery mildew fungi in
      agriculture and nature.

PMID- 18036856
TI  - Interaction of reactive oxygen and nitrogen species with albumin- and
      methemoglobin-bound dinitrosyl-iron complexes.
AB  - Destructive effect of superoxide anions O2- derived from KO(2) or xanthine
      xanthine oxidase system on dinitrosyl-iron complexes bound with bovine albumin or
      methemoglobin (DNIC-BSA or DNIC-MetHb) was demonstrated. The sensitivity of DNIC
      BSA synthesized by the addition of DNIC with cysteine, thiosulfate or phosphate
      (DNIC-BSA-1, DNIC-BSA-2 or DNIC-BSA-3, respectively) to destructive action of O2-
      decreased in row: DNIC-BSA-1>DNIC-BSA-3>DNIC-BSA-2. The estimated rate constant
      for the reaction between O2- and DNIC-BSA-3 was equal to approximately 10(7)M(
      1)s(-1). However, hydrogen peroxide and tert-butyl hydrogenperoxide (t-BOOH) did
      not induce any noticeable degradation of DNIC-BSA-3 even when used at
      concentrations exceeding by one order of magnitude those of the complex. As to
      their action on DNIC-MetHb both hydrogen peroxide and t-BOOH-induced rapid
      degradation of the complex. Both agents could induce the process due to the
      effect of alkylperoxyl or protein-derived free radicals formed at the interaction
      of the agents with ferri-heme groups of MetHb. Peroxynitrite (ONOO(-)) could also
      initiate protein-bound DNIC degradation more efficiently in the reaction with
      DNIC-BSA-3. Higher resistance of DNIC-MetHb to peroxynitrite was most probably
      due to the protective action of heme groups on ONOO(-). However, the analysis
      allows to suggest that the interaction of protein-bound DNICs with O2- is the
      only factor responsible for the degradation of the complexes in cells and
      tissues.

PMID- 18036857
TI  - Diagnosis and treatment of Eimeria macusaniensis in an adult alpaca with signs of
      colic.
AB  - A young adult pregnant alpaca was presented with an acute episode of abdominal
      pain. Hematology revealed mild anemia, neutropenia with a degenerative left shift
      and moderate toxic changes in neutrophils, hyperfibrinogenemia, hypoproteinemia,
      and hypoalbuminemia. Abdominal ultrasound showed a small intestinal segment with
      severely increased wall thickness and collapsed lumen. Exploratory laparotomy
      revealed a markedly thickened 60cm jejunal segment with reddened serosa from
      which a full-thickness biopsy and samples for bacterial culture were obtained.
      Histopathology revealed severe coccidian enteropathy with secondary bacterial
      enteritis. Anaerobic culture yielded Clostridium perfringens, while fecal sugar
      flotation yielded Eimeria macusaniensis and Eimeria punoensis. The alpaca was
      treated with broad-spectrum antimicrobial drugs, sulfadimethoxine, and anti
      inflammatory drugs. The alpaca made a gradual recovery and had a term pregnancy.
      This communication demonstrates the potential pathogenicity of E. macusaniensis
      in adult alpacas. Coccidian enteropathy should be considered in adult alpacas
      with gastrointestinal signs including acute abdominal pain and hypoproteinemia.

PMID- 18036858
TI  - The effect of local anaesthesia on anaesthetic requirements for feline
      ovariectomy.
AB  - A dose of supplementary ketamine was used to evaluate the anaesthetic sparing
      effect of adding local anaesthesia to general anaesthesia in cats undergoing
      ovariectomy. Fifty-six healthy cats were randomly assigned to receive lidocaine
      2% (group L) as skin infiltration (1 mg kg(-1)), topical application (splash
      block) on both the ovaries (2 mg kg(-1), each) and on abdominal muscular layers
      (1 mg kg(-1)), or an equal volume of NaCl 0.9% at the same sites (group S).
      Anaesthesia was induced with a mixture of 20 microg kg(-1) medetomidine and 5 mg
      kg(-1) ketamine administered intramuscularly. Rectal temperature, ECG, heart rate
      and respiratory rate were measured continuously. Ketamine supplemental boli (1 mg
      kg(-1), intravenously) were administered in response to movements during surgery.
      Local lidocaine significantly reduced the need for supplementary ketamine. All
      animals were returned to their owners without complications. With this protocol,
      local anaesthetics reduced the need for injectable anaesthetic during feline
      ovariectomy.

PMID- 18036859
TI  - Moving from preventing HIV/AIDS in its infancy to preventing family illness and
      death (PFID).
AB  - In April 2007, UNAIDS released Securing the future--advocating for children, a
      call for the global community to recognize that "children still remain largely
      absent from national and international political responses to the AIDS pandemic".
      Most efforts to date to protect children from HIV have focused on prevention of
      mother-to-child transmission (PMTCT) programs. Though expanding PMTCT programs,
      particularly in sub-Saharan Africa, are crucial, even widespread PMTCT programs
      would still be grossly inadequate for achieving the goal of protecting children
      from HIV/AIDS. The global community needs to fundamentally reframe its approach
      to HIV prevention to fully address the health of families, otherwise the future
      for at-risk children is likely to remain bleak. After identifying challenges with
      current approaches, we review recent research that provides insights into ways
      prevention programs may be adapted to better protect families and children from
      the devastating consequences of HIV/AIDS. Only by protecting families from
      HIV/AIDS will we be able to achieve the goal of an AIDS-free generation.

PMID- 18036860
TI  - Pemphigus and HLA in Morocco.
AB  - PURPOSE OF STUDY: Pemphigus is a group of autoimmune bullous dermatosis diseases
      characterized by autoantibodies against keratinocyte adhesion molecule. A
      significant association with HLA class II genes, particularly DR4 and DR14 has
      been described in many ethnic groups and countries. We have investigated, for the
      first time in Morocco the relationship between different pemphigus subtypes and
      HLA genes. PATIENTS AND METHODS: Fifty-two unrelated patients were compared to
      178 healthy controls matched by age, sex and ethnic origin. HLA typing was
      performed by standard complement dependent microlymphocytotoxic method for class
      I and by sequence-specific primer amplification method for class II. RESULTS: No
      significant association was observed with any of the HLA-A or -B antigens.
      Generic typing showed a significant increase of DRB1*04 (p=0.002), DRB1*14
      (p=0.003) and DQB1*03 (p=0.02) allele frequencies and significant decrease of
      DRB1*15 (p<0.0001) and DQB1*06 (p=0.01) allele frequencies. HLA-DRB1*15-DQB1*06
      haplotype seems to confer a protective effect in our population while DRB1*04
      DQB1*03 and DRB1*14-DQB1*05 haplotypes induced susceptibility to the disease.
      CONCLUSION: Taken together, our results confirmed the genetic predisposition to
      pemphigus. However, genetic factors are not sufficient to explain the high
      prevalence of pemphigus observed in the Moroccan population since alleles of
      susceptibility were similar to those commonly described in other populations
      throughout the world.

PMID- 18036862
TI  - Long-term strategy in the management of postmenopausal osteoporosis.
AB  - The lifetime fracture risk at 50 years of age is about 50% in women and 20% in
      men. Osteoporotic fractures are associated with severe morbidity, increased
      mortality, quality-of-life alterations, and high management costs, most notably
      in the oldest age groups. The steady increase in life expectancy is matched by a
      rise in the absolute fracture risk. Effective prevention is therefore crucial.
      The goal of prevention, which must be not only effective, but also safe, is to
      diminish the risk of vertebral, peripheral, and hip fractures. Several
      medications were effective in double-blind controlled trials in which the
      fracture incidence was the primary endpoint. Long-term data are available to
      confirm the good safety profile of these medications.

PMID- 18036861
TI  - Osteopontin is an argentophilic protein in the bone matrix and in cells of kidney
      convoluted tubules.
AB  - Nucleolar organising regions (NOR) are part of the nucleolus, containing
      argyrophilic proteins (nucleoclin/C23, nucleophosmin/B23). They are identified by
      silver staining at low pH. The method also reveals osteocyte canaliculi and
      cement lines and granules in the cytoplasm of kidney cells in locations that
      mimic osteopontin distribution. Human bone and kidney sections, benign and
      lymphomatous pleural effusions were processed for silver staining to identify
      AgNOR. Sections were processed in parallel for immunohistochemistry with an
      antibody direct against osteopontin. In pleural effusions, AgNORs were found
      increased in the nuclei of lymphoma cells. In bone, Ag staining identified AgNOR
      in cell nuclei, as well as in osteocyte canaliculi, cement and resting lines. In
      the distal convoluted tubules of the kidney, silver deposits were also observed
      in cytoplasmic granules on the apical side of the cells. Immunolocalization of
      osteopontin closely matched with all these locations in bone and kidney. NOR
      proteins and osteopontin are proteins containing aspartic acid rich repeats that
      can bind Ag. Staining protocols using silver nitrate at low pH can identify these
      proteins on histological sections. AgNOR is a useful histochemical method to
      identify osteopontin in bone sections.

PMID- 18036863
TI  - Natural history or outcome with conservative treatment of degenerative rotator
      cuff tears.

PMID- 18036865
TI  - State-of-the-art retinal optical coherence tomography.
AB  - OCT functions as a type of optical biopsy, providing information on retinal
      pathology in situ and in real time, with resolutions approaching that of
      excisional biopsy and histopathology. The development of ultrabroad-bandwidth and
      tunable light sources, as well as high-speed Fourier detection techniques, has
      enabled a significant improvement in ophthalmic optical coherence tomography
      (OCT) imaging performance. Three-dimensional, ultrahigh-resolution OCT (UHR OCT)
      can provide information on intraretinal morphology that is not available from any
      other non-invasive diagnostic. High-speed imaging facilitates the acquisition of
      three-dimensional data sets (3D-OCT), thus enabling volumetric rendering and the
      generation of OCT fundus images that precisely and reproducibly register OCT
      images to fundus features. The development of broadband light sources emitting at
      new wavelengths, e.g., approximately 1050 nm, has enabled not only 3D-OCT imaging
      with enhanced choroidal visualization, but also reduced scattering losses and
      improved OCT performance in cataract patients. Adaptive optics using high-stroke,
      deformable mirror technology to correct higher order aberrations in the human
      eye, in combination with specially designed optics to compensate chromatic
      aberration along with three-dimensional UHR OCT, has recently enabled in vivo
      cellular-resolution retinal imaging. In addition, extensions of OCT have been
      developed to enhance image contrast and to enable non-invasive depth-resolved
      functional imaging of the retina, thus providing blood flow, spectroscopic,
      polarization-sensitive and physiological information. Functional OCT promises to
      enable the differentiation of retinal pathologies via localized, functional
      retinal response or metabolic properties. These advances promise to have a
      powerful impact on fundamental as well as clinical studies.

PMID- 18036864
TI  - Micro-fine finishing of a feldspar porcelain for dental prostheses.
AB  - Intraoral adjustment of ceramic prostheses involving micro-finishing using
      diamond burs is a critical procedure in restorative dentistry because the
      durability of a restoration depends on the finishing process and quality. Force,
      energy and surface integrity in micro-fine finishing of a feldspar porcelain
      versus operational parameters were investigated using a 2-DOF (two-degrees-of
      freedom) high-speed dental handpiece and a fine diamond bur of 20-30 microm
      grits. The tangential and normal forces were measured as being significantly
      small in the ranges 0.18-0.35 N and 0.22-0.59 N, respectively. High specific
      finishing energy of 110-2523J/mm(3) was observed in material removal,
      particularly when decreasing either the depth of cut or the feed rate. Scanning
      electron microscopy observations indicated that the surfaces generated were
      mainly due to ductile flow; however, microfractures also occurred in porcelain.
      Surface roughness was measured as 0.43-0.74 microm in terms of arithmetic mean
      value (R(a)), decreasing with the depth of cut, but insignificantly changing with
      the feed rate (ANOVA, P>0.05). Recommendations for clinical practice are made on
      the basis of our testing results.

PMID- 18036866
TI  - Contextual factors and immigrants' health status: double jeopardy.
AB  - Poor health among immigrants may be accounted for not only by socio-economic
      factors affecting individuals but also by the environment in which they live. We
      investigated the association of contextual factors with disparities in self-rated
      health between native and immigrant groups. The findings indicated that, compared
      with native-born Belgians, immigrant groups from Turkey and Morocco were more
      likely to have poorer self-rated health. When contextual factors and individual
      socio-economic status were allowed for, all immigrant groups had a health status
      that was similar to or even better than that of native-born Belgians. Immigrants
      face a double jeopardy at both the individual and the contextual level.

PMID- 18036867
TI  - Mediating medical risk factors in the residential segregation and low birthweight
      relationship by race in New York City.
AB  - This study explores mediating medical risk factors in the association between
      racial residential segregation (i.e., racial 'black' isolation) and low
      birthweight in New York City, adjusting for maternal and infant risk factors and
      neighborhood poverty. This race-specific cross-sectional multilevel study found
      that as racial isolation increased in neighborhoods, the odds of having a low
      birthweight infant also increased for African-American and White women living in
      these areas. Medical conditions that mediated the racial isolation and low
      birthweight relationship included chronic hypertension and pregnancy-related
      hypertension for African-American women and chronic hypertension and lung disease
      for White women. Although this study was limited by the quality of the birth
      certificate data, it does provide exploratory pathways by which medical risks and
      their sequelae are linked to neighborhood environments and reproductive
      vulnerability.

PMID- 18036870
TI  - Study of the absorption and emission spectroscopy of "A-B" type photosensitive
      compounds including two-photon chromophore and benzophenone moiety.
AB  - "A-B" type photosensitive compounds including two-photon chromophore and
      benzophenone moiety have been designed, synthesized and characterized. The UV-vis
      absorption and fluorescence emission of the compounds have been extensively
      studied in various solvents. The results show that the absorption of "A-B" type
      compounds displays obvious double absorption bands, one of which at short
      wavelength is related to the benzophenone moiety, the other at long-wavelength is
      mainly contributed by chromophore. The emission of "A-B" type compounds at 500
      700 nm shows an "unexpected" blue-shift comparing with that of the sole
      chromophore. The photosensitive compounds with amino group display strong
      emission in apolar solvents and have a low fluorescence quantum yields in polar
      solvents. In contrast, the compounds without amino group exhibit strong
      fluorescence emission in polar solvents, and low fluorescence quantum yields in
      apolar solvents. The fluorescence quantum yields of "A-B" type compounds are
      higher than those of the sole chromophore. The discoveries suggest that charge
      redistribution induced by the introduction of benzophenone moiety plays a key
      role on the absorption and emission spectroscopy.

PMID- 18036868
TI  - The function of the NADPH oxidase of phagocytes and its relationship to other
      NOXs in plants, invertebrates, and mammals.
AB  - The NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (NOX) of
      'professional' phagocytic cells transfers electrons across the wall of the
      phagocytic vacuole, forming superoxide in the lumen. It is generally accepted
      that this system promotes microbial killing through the generation of reactive
      oxygen species and through the activity of myeloperoxidase. An alternative
      scenario exists in which the passage of electrons across the membrane alters the
      pH and generates a charge that drives ions into, and out of, the vacuole. It is
      proposed that the primary function of the oxidase is to produce these pH changes
      and ion fluxes, and the issues surrounding these processes are considered. The
      neutrophil oxidase is the prototype of a whole family of NOXs that exist
      throughout biology, from plants to man, which might function, at least in part,
      in a similar fashion. Some examples of how these other NOXs might influence ion
      fluxes are examined.

PMID- 18036871
TI  - An intramolecular charge transfer fluorescent probe: synthesis and selective
      fluorescent sensing of Ag+.
AB  - An intramolecular charge transfer (ICT) fluorescent probe, in which the thiourea
      derivative moiety is linked to the fluorescent 4-(dimethylamino) benzamide, has
      been designed and synthesized. The ions-selective signaling behaviors of the
      probe were investigated. Upon the addition of Ag+, an overall emission
      enhancement of 14-fold was observed. Compound 1 displayed highly selective
      chelation enhanced fluorescence (CHEF) effect with Ag+ over alkali, alkali earth
      metal ions and some transition metal ions in aqueous methanol solutions. The
      prominent selective and efficient fluorescent enhancing behavior could be
      utilized as a new chemosensing probe for the analysis of Ag+ ion in aqueous
      environment.

PMID- 18036872
TI  - Pars planitis: a 20-year study of incidence, clinical features, and outcomes.
AB  - PURPOSE: To measure the incidence of pars planitis in a community-based
      population and to report clinical features, complications, and visual prognosis.
      DESIGN: Population-based, retrospective, 20-year cohort study. METHODS:
      Multicenter study using the Rochester Epidemiology Project medical records
      linkage system, which allows analysis of almost all patients within Olmsted
      County, Minnesota, with a given medical condition. Databases were searched to
      identify all patients with pars planitis from January 1, 1985 through December
      31, 2004. Forty-six eyes of 25 patients were evaluated. RESULTS: Mean follow-up
      was 14.3 years. The incidence of pars planitis was 2.077 per 100,000 persons (95%
      confidence interval [CI], 1.43 to 2.62). The most common complications were
      epiretinal membrane (ERM) in 17 eyes (36%), cataract in 14 eyes (30.4%), and
      cystoid macular edema (CME) in 12 eyes (26.1%). Mean visual acuity after 10 years
      of follow-up was 20/30, with 18 of 24 patients maintaining a visual acuity of
      20/40 or better. One-third of patients maintained normal visual acuity without
      requiring treatment. CONCLUSIONS: The visual prognosis of pars planitis is
      relatively good, with 75% of patients maintaining a visual acuity of 20/40 or
      better after 10 years. Many patients with mild disease do not require treatment.
      A subset of patients, however, experience severe disease with severe vision loss
      despite treatment. The rate of smoking and multiple sclerosis in patients with
      pars planitis is much higher than that of the general population.

PMID- 18036873
TI  - Verteporfin therapy of subfoveal occult choroidal neovascularization in AMD using
      delayed light application: one-year results of the VALIO Study.
AB  - PURPOSE: To compare photodynamic therapy (PDT) with verteporfin (Visudyne;
      Novartis Pharma AG, Basel, Switzerland) using either standard or delayed light
      application. DESIGN: Phase II, multicenter, masked, randomized clinical trial.
      METHODS: Sixty patients with occult with no classic choroidal neovascularization
      (CNV) resulting from age-related macular degeneration were assigned randomly
      (1:1) to verteporfin infusion followed by light application either at 15 minutes
      (standard light) or 30 minutes (delayed light) after the start of the infusion.
      The assigned treatment was repeated every three months if fluorescein leakage was
      detected. RESULTS: At month 12, patients lost a mean of 15.7 letters and 11.4
      letters from baseline in the standard and delayed light groups, respectively (P =
      .38). Twelve (52%) of 23 patients in the standard light group and 11 (42%) of 26
      in the delayed light group lost at least 15 letters of visual acuity (P = .57).
      CONCLUSIONS: There were no statistically significant differences between
      verteporfin therapy using the delayed light regimen of 30 minutes or the standard
      light regimen of 15 minutes in eyes with occult with no classic CNV.

PMID- 18036874
TI  - Retinal vein occlusions and mortality: the Beijing Eye Study.
AB  - PURPOSE: To assess the association between retinal vein occlusion (RVO) and
      mortality in a population-based setting. DESIGN: Population-based, longitudinal
      study. METHODS: At baseline in 2001, the Beijing Eye Study examined 4,335
      subjects for RVO with a frequency of detected vein occlusions of 61 (1.4%) in
      4,335 subjects. In 2006, all study participants were invited for a follow-up
      examination. RESULTS: Of the 4,335 subjects, 3,195 (73.7%) returned for follow-up
      examination, whereas 132 (3.0%) subjects had died and 1,008 (23.3%) subjects
      declined to be re-examined or had moved away. For the subjects younger than 70
      years or than 65 years, respectively, RVO was associated significantly with an
      increased mortality rate (P = .05; 95% confidence interval [CI], 0.995 to 8.26;
      and P = .001; 95% CI, 2.11 to 18.73, respectively). CONCLUSIONS: RVO in
      relatively young persons may signal a significant risk of mortality.

PMID- 18036875
TI  - LOXL1 mutations are associated with exfoliation syndrome in patients from the
      midwestern United States.

PMID- 18036876
TI  - Re: The use of the femtosecond laser in penetrating keratoplasty.

PMID- 18036877
TI  - Re: Maculopathy as a complication of blood-brain barrier disruption in patients
      with central nervous system lymphoma.

PMID- 18036879
TI  - Posterior chamber vs anterior chamber intraocular lenses after vitreous
      presentation in the presence of adequate capsular support.

PMID- 18036880
TI  - Re: Ectatic disorders associated with a claw-shaped pattern on corneal
      topography.

PMID- 18036883
TI  - Re: Prostaglandin E(2) inhibition and aqueous concentration of ketorolac 0.4% and
      nepafenac 0.1% in patients undergoing phacoemulsification.

PMID- 18036885
TI  - Do general practitioners change how they use the computer during consultations
      with a significant psychological component?
AB  - OBJECTIVES: To describe the patterns of computer use during patient visits to
      family doctors and to determine whether doctors alter their pattern of computer
      use in consultations which have significant psychological content. DESIGN:
      Observational, non-randomised cluster trial with data being collected from
      videotaped consultations. SETTING: Three inner-city Family Practice offices
      involved in physician training in Belfast, Northern Ireland. PARTICIPANTS: Ten
      family doctors, who declared using computers during their consultations and
      consecutive consenting adult patients attending these doctors. RESULTS: One
      hundred consultations were videotaped (59% patient participation rate). The
      average consultation time was 9min 48s, and number of problems per consultation
      was 1.9. Three broad styles of computer use were defined: (1) "end users" who
      only used the computer at the end of a consultation to summarise the
      consultation, (2) "continuous users", who interacted with the computer throughout
      the consultation, and (3) "minimal users", who only ever used the computer at the
      end of the consultation mostly to issue prescriptions. Of the 100 consultations
      videoed 37% were of a psychological nature. Consultations with psychological
      content were on average longer (11min 47s vs. 8min 39s) and the average
      percentage time doctors spent on the computer was about half that of non
      psychological consultations (11% vs. 23% and p<0.001). CONCLUSION: The doctors
      were found to adopt one of three broad styles of computer use during their
      consultations. In consultations with observable significant psychological content
      doctors significantly reduce the proportion of time at the computer suggesting an
      ability to appropriately tailor their use of the computer during consultations.

PMID- 18036887
TI  - In vitro inhibition of coronavirus replications by the traditionally used
      medicinal herbal extracts, Cimicifuga rhizoma, Meliae cortex, Coptidis rhizoma,
      and Phellodendron cortex.
AB  - BACKGROUND: A search for new anti-coronaviral drugs to treat coronaviral
      infections was motivated by an outbreak of severe acute respiratory syndrome
      (SARS). OBJECTIVES: In order to find drugs that treat coronavirus infections,
      including SARS, we screened traditional medicinal herbal extracts and evaluated
      their antiviral activities on coronavirus replication. STUDY DESIGN: We employed
      a plaque assay to evaluate the effect of 22 medicinal herbal extracts on virus
      replication. We determined the 50% effective concentration (EC50) of each extract
      that was necessary to inhibit the replication of mouse hepatitis virus A59 (MHV
      A59); we also determined 50% cytotoxic concentrations (CC50) for each extract.
      Northern and Western blot analyzes were performed to investigate antiviral
      activity in MHV-infected DBT cells, including virus entry, viral RNA and protein
      expression, and virus release. Coronavirus specific inhibition was also
      demonstrated using porcine epidemic diarrhea virus (PEDV). RESULTS: Cimicifuga
      rhizoma, Meliae cortex, Coptidis rhizoma, Phellodendron cortex and Sophora
      subprostrata radix decreased the MHV production and the intracellular viral RNA
      and protein expression with EC50 values ranging from 2.0 to 27.5 microg/ml. These
      extracts also significantly decreased PEDV production and less dramatically
      decreased vesicular stomatitis virus (VSV) production in vitro. CONCLUSIONS: The
      extracts selected strongly inhibited MHV replication and could be potential
      candidates for new anti-coronavirus drugs.

PMID- 18036888
TI  - Comparison of AMPLICOR and Hybrid Capture II assays for high risk HPV detection
      in normal and abnormal liquid-based cytology: use of INNO-LiPA Genotyping assay
      to screen the discordant results.
AB  - The study was aimed to evaluate the feasibility of detecting human papillomavirus
      (HPV) in women with normal or abnormal cervical smears using the Roche Amplicor
      MWP HPV Test. We compared by AMPLICOR Test and Hybrid Capture II (HCII) Test, the
      prevalence of HR-HPV in 470 cervical samples including 55 samples with WNL
      cytology, 208 ASC-US, 193 LGSIL and 14 HGSIL. Samples with discordant results
      were retested with INNO-LiPA Genotyping HPV Test v2. The HR-HPV positivity in WNL
      cytology samples was similar (21.8%) by AMPLICOR and HCII. In ASC-US, the HPV
      positivity was 42.3% by both tests. In LGSIL, HPV positivity was 66.3% and 66.8%
      by AMPLICOR and HCII, respectively. In HGSIL, 92.8% of samples were positive by
      AMPLICOR and 85.7% by HCII. The agreement of both tests was 96.2% with a Kappa
      value of 0.92. Eighteen cases were discordant: 9 HCII positive/AMPLICOR negative
      and 9 HCII negative/AMPLICOR positive. The INNO-LiPA test revealed HPV positivity
      in every case. Interestingly, all HCII+/AMPLICOR- samples were found to harbour
      HPV53. As for the HCII-/AMPLICOR+ samples, 8 demonstrated a multiple infection
      with HR 16- and/or 18- and/or 56-phylogenetically related HPV types. Moreover,
      two of these samples were co-infected with HPV6 and two other with HPV54. By
      using consensus HR-HPV as our reference HPV positivity, the sensitivity (96.6%)
      and specificity (100%) of AMPLICOR was similar to that of HCII Test. The AMPLICOR
      HPV Test is sensitive, specific, feasible and appropriate for routine HPV
      detection.

PMID- 18036889
TI  - Surgical treatment of epiphrenic diverticula: a 30-year experience.
AB  - BACKGROUND: Epiphrenic diverticula are rare and associated with esophageal
      motility abnormalities. Their optimal surgical treatment is debated, mortality
      being 9% in the largest reported surgical series of 33 patients. Our experience
      with a traditional thoracic approach was reviewed to provide benchmark data
      against which newer surgical techniques can be measured. METHODS: A retrospective
      review of 35 patients operated on for epiphrenic diverticula from 1976 to 2005
      was conducted. All underwent open transthoracic operations: resection of the
      diverticulum, long esophagomyotomy, and antireflux operations (modified Belsey,
      29 patients; Nissen, 4 patients) in 33 patients; resection and long myotomy alone
      in 1 patient; and plication, long myotomy, and Collis-Nissen in 1 patient.
      Preoperative assessment included barium esophagogram, flexible esophagoscopy,
      manometry, and standard acid reflux test. Operative complications and functional
      results were assessed. RESULTS: Median age was 71 years (range, 36 to 87 years).
      Diverticulum size averaged 6.4 cm (range, 3 to 14 cm). Sixty-eight percent
      presented to the right of the esophagus. The median duration of symptoms was 3
      years. Presenting complaints included dysphagia (83%), regurgitation (69%), and
      chest pain (26%). Eighteen had a mean weight loss of 19 pounds. There was 1
      perioperative death (2.8%) from a plicated diverticulum leak and one nonfatal
      suture line leak. Median hospital stay was 7 days. Mean follow-up was 45.3
      months. Twenty-six patients (74%) had an excellent result (no residual symptoms).
      Seven required a periodic esophageal dilatation for intermittent mild dysphagia.
      CONCLUSIONS: Traditional transthoracic resection, long esophagomyotomy, and an
      antireflux procedure provide excellent long-term functional results with
      relatively low postoperative morbidity in patients with epiphrenic diverticula.

PMID- 18036890
TI  - Long-term outcome of surgical treatment for non-small cell lung cancer with
      comorbid liver cirrhosis.
AB  - BACKGROUND: Long-term outcome of surgery for non-small cell lung cancer with
      comorbid liver cirrhosis is not well known. We aimed to establish the factors
      influencing survival in such cases. METHODS: We retrospectively reviewed 33
      patients who had undergone surgery for non-small cell lung cancer with comorbid
      liver cirrhosis. Clinical features, early outcome, survival time, and cause of
      death were investigated. Factors influencing survival were estimated by
      univariate and multivariate analyses. RESULTS: There were 2 in-hospital deaths
      (6.5%). Five-year survival rate for lung cancer death (n = 9) was 59.7%, whereas
      for hepatic death (n = 6), it was 62.9%. Factors influencing lung cancer death
      were nodal stage and limited resection (p < 0.05 for each). Factors influencing
      hepatic death were serum total bilirubin (p < 0.0001) and cholinesterase (p <
      0.05), platelet count (p < 0.05), and alpha-fetoprotein (p < 0.05). Lung disease
      factors such as local extensiveness of the tumor and pathologic stage, and
      surgical factors such as performance of mediastinal dissection and limited
      surgery, also influenced survival from hepatic death (p < 0.05 for each).
      CONCLUSIONS: Although pulmonary resection invasiveness may have some impact on
      long-term liver function, the life expectancy of patients with cirrhosis does not
      seem to be severely affected by pulmonary resection itself. Curative surgery
      should be performed if possible, even in patients with cirrhosis.

PMID- 18036891
TI  - Completely resected non-small cell lung cancer: reconsidering prognostic value
      and significance of N2 metastases.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) mediastinal (N2) metastases are
      indicators of poor prognosis. Survival rates decrease with increasing number of
      N2 stations and involved lymph nodes as well as lymph node size and capsular
      invasion. Our purpose was to elucidate the impact lymph node-related variables on
      the outcome after surgical resection. METHODS: We reviewed data of 2344 NSCLC
      patients who underwent curative resections with mediastinal lymphadenectomy, and
      586 (25%) had N2 metastases. We studied the overall survival of N2 patients
      according to some important covariates. RESULTS: Metastases involved single N2
      stations in 386 patients (66%) and two or more in 200 (34%). Survival was not
      related with histology or pathologic tumor (pT), but was better when only one N2
      station was involved (5-year overall survival 28.5% [median, 24 months] versus
      17.2% [median, 14 months] respectively; p = 0.0002. For single N2 stations,
      capsular rupture, number, and size of lymph nodes were not significant prognostic
      factors. When the size of lymph node was analyzed (micrometastases, 53; nonbulky,
      207; or bulky metastases, 126), overall survival differences between nonbulky and
      bulky N2 were significant: 5-year overall survival was 34% (median, 28 months)
      versus 23% (median, 23 months), respectively (p = 0.026). Presence of
      micrometastases was associated with a poor prognosis: 5-year overall survival of
      21.4% (median, 23 months). CONCLUSIONS: Prognosis was better for patients with
      single N2 stations when metastatic lymph nodes were not enlarged. However, the
      presence of lymph nodes micrometastases does not seems associated with a better
      outcome.

PMID- 18036892
TI  - Effect of formalin fixation on tumor size determination in stage I non-small cell
      lung cancer.
AB  - BACKGROUND: Tumor size is an important prognostic factor in non-small cell lung
      cancer (NSCLC), but the American Joint Committee on Cancer staging system does
      not mandate a specific measurement method. Moreover, measuring fresh specimens
      and formalin-fixed specimens may yield disparate results. Our goal was to
      evaluate this disparity for stage I NSCLC. METHODS: We enrolled 401 patients with
      stage I NSCLC who underwent surgical interventions and follow-up in our hospital
      between 1993 and 2002. Tumors invading visceral pleura, involving the main
      bronchus, or associated with atelectasis or obstructive pneumonitis were
      excluded. Tumor size was measured immediately after resection by surgeons and
      after formalin fixation by pathologists. Patients were assigned to one of three
      groups. Group 1 included 201 patients with tumors of 3 cm or less as indicated by
      both operation notes and pathology reports. Group 2 included 160 patients with
      tumors larger than 3 cm by both records. Group 3 included 40 patients with tumors
      larger than 3 cm according to operation notes but 3 cm or less according to
      pathology reports. Survival rates were compared. RESULTS: Mean follow-up was 58
      months. Five-year survival was 70.1% in group 1, 49.1% in group 2, and 51.1% in
      group 3. As expected, there was a significant survival difference between groups
      1 and 2 (p < 0.001); however, there was also a difference between groups 1 and 3
      (p = 0.006). CONCLUSIONS: Formalin fixation may cause tumor shrinkage and
      migration from T2 to T1. For accurate tumor staging, size measurements should be
      performed immediately after resection instead of after formalin fixation. TNM
      staging should specify how to measure tumor size and the specimen status to be
      measured.

PMID- 18036893
TI  - Helical computed tomography inaccuracy in the detection of pulmonary metastases:
      can it be improved?
AB  - BACKGROUND: In thoracic surgery, manual lung palpation for detection of pulmonary
      metastases during resection is the standard of care, despite improvements in
      computed tomography (CT) imaging. In our previous study based on chart review
      alone, the accuracy of helical CT in the detection of pulmonary metastases was
      surprisingly low, with a sensitivity of 78%. We hypothesized that this may be
      improved by scan interpretation with adequate clinical history and focused
      documentation of all pulmonary lesions, and may be influenced by the training of
      the reader. METHODS: Preoperative CT scans of 53 patients undergoing 60 cases of
      pulmonary metastasectomy at our center from 1996 to 2004 were retrospectively
      reviewed by a dedicated chest radiologist and a non-chest radiologist. Nodules
      detected on preoperative helical CT were compared with pathologically confirmed
      metastases. RESULTS: In 27 of 59 (46%) cases read by radiologist 1, and 27 of 58
      (47%) cases read by radiologist 2, metastases found by lung palpation were not
      seen on preoperative CT. Preoperative CT was entirely correct (no missed
      metastases or false-positive lesions) in only 11 of 59 (19%) of cases read by
      radiologist 1, and 11 of 58 (19%) of cases read by radiologist 2. CONCLUSIONS:
      Helical CT misses metastases in 46% to 47% of cases. Accuracy of preoperative CT
      scanning for detection of pulmonary metastases was not improved with the
      provision of clinical history to the reader, nor was it influenced by the
      interpreter's training. A combined approach to pulmonary metastasectomy including
      preoperative and postoperative CT as well as manual lung palpation is necessary
      to render the patient disease-free.

PMID- 18036894
TI  - Invited commentary. The accuracy in detecting pulmonary metastases.

PMID- 18036895
TI  - Readmission to intensive care unit after initial recovery from major thoracic
      oncology surgery.
AB  - BACKGROUND: Little has been published regarding outcomes subsequent to
      complications after thoracic surgery. The present study investigated outcomes and
      risk factors associated with mortality in patients admitted to an intensive care
      unit (ICU) after initial recovery from thoracic oncology surgery. METHODS: From
      March 2001 to August 2005, 1,087 patients underwent major resection for lung or
      esophageal cancer. Ninety-four (8.6%) of those patients required ICU care after
      initial recovery, and were the subject of the present retrospective review.
      RESULTS: The patient group included 85 males (90.4%), of mean age 66 years.
      Patients were classified as either survivors (n = 63, 67%) or nonsurvivors (n =
      31, 33%). The most common reason for ICU readmission was pulmonary complication
      (n = 73, 77.7%). Sixty-four patients (68.1%) required mechanical ventilation and
      42 (43.3%) required renal support. Multivariate analysis showed that the initial
      acute physiological assessment and chronic health evaluation (APACHE) III score
      at readmission to ICU, duration of mechanical ventilation, and renal support were
      risk factors for in-hospital mortality. The overall three-year survival was
      50.6%. Cox analysis showed that survivors who underwent tracheostomy had a poor
      prognosis (p = 0.011). Of 12 late mortalities in survivors who underwent
      tracheostomy, 9 (75%) were due to cancer-unrelated causes. CONCLUSIONS: The ICU
      readmission after thoracic oncology surgery was associated with high in-hospital
      mortality. Identification of patients with a high APACHE score and (or) prolonged
      ventilation at readmission may help predict the risk of mortality. Preemptive
      strategies designed to optimize treatment of such high-risk patients may improve
      outcomes. Survivors from ICU readmission after thoracic oncology surgery require
      meticulous and frequent follow-up due to a high risk of deterioration after
      discharge.

PMID- 18036897
TI  - Invited commentary. Surgical correction of a hernia has to be identified in the
      early postoperative period, regardless of symptoms.

PMID- 18036898
TI  - Foreign bodies in the esophagus.
AB  - BACKGROUND: One third of foreign bodies retained in the gastrointestinal tract
      are present in the esophagus. Their management depends on the anatomic location,
      shape and size of the foreign body, and duration of impaction. METHODS: Between
      1971 and 2001, 32 patients with foreign bodies in the esophagus were admitted to
      our service in the Wolfson Medical Center. Their charts were reviewed for
      preoperative diagnosis, kind and location of foreign body, length of retention,
      management of patients, complications, and length of hospitalization. RESULTS:
      One patient was admitted with perforation of the esophagus. Thirty of the foreign
      bodies have been extracted at rigid esophagoscopy and two at thoracotomy. There
      was one complication (tear of esophageal mucosa) and one death. CONCLUSIONS: The
      presence of a foreign body in the esophagus is a challenging problem.
      Perforations may result in death. Impaction mandates immediate extraction. Our
      experience indicates that the use of a rigid esophagoscope is safe and reliable.
      Based on this experience and that of other authors, we recommend the use of the
      rigid endoscope as the instrument of choice for extracting foreign bodies from
      the esophagus. Surgeons in training should be taught rigid esophagoscopy.

PMID- 18036896
TI  - Diaphragmatic hernia after conventional or laparoscopic-assisted transthoracic
      esophagectomy.
AB  - BACKGROUND: Diaphragmatic herniation is a rare but morbid complication after
      esophagectomy. This retrospective study estimates its incidence after
      transthoracic esophagectomy and describes the clinical spectrum of diaphragmatic
      herniation. METHODS: Between February 1, 1997, and June 31, 2007, 355 consecutive
      patients with esophageal cancer underwent transthoracic esophagectomy. A
      diaphragmatic hernia was detected in 9 patients (2.5%) after transthoracic
      esophagectomy. All patients were men, with a median age of 50 years. A
      retrospective analysis of clinicopathologic characteristics of these patients was
      performed. RESULTS: The median time between esophagectomy and diagnosis of
      herniation was 8 months. The 9 patients presented with different degrees of
      symptoms: 3 were asymptomatic, 2 had minor symptoms, and 4 had acute symptoms.
      All had a herniation of abdominal organs into the left hemithorax. One patient
      was asymptomatic, and no surgical repair was performed. Another patient refused
      the recommended reoperation. The other 7 patients underwent surgical repair of
      the diaphragmatic hernia by an abdominal approach. All had reduction of the
      herniated bowel into the abdominal cavity and closure of the hiatal defect.
      Resection of small bowel was performed in 1 patient for strangulation, and
      another patient underwent splenectomy for bleeding. Median hospital stay was 16
      days. One patient died secondary to mediastinitis from an anastomotic leakage of
      the esophagogastrostomy. CONCLUSIONS: Diaphragmatic herniation after
      esophagectomy mostly occurs into the left chest. Surgeons should be aware of this
      rare complication in patients presenting with symptoms of intestinal obstruction
      or respiratory complaints after esophagectomy.

PMID- 18036899
TI  - Sutureless pneumostasis using polyglycolic acid mesh as artificial pleura during
      video-assisted major pulmonary resection.
AB  - BACKGROUND: Postoperative air leaks impede rehabilitation and prolong
      hospitalization after pulmonary resection. To promote rehabilitation after video
      assisted major pulmonary resection, we attempted to control alveolar air leaks
      without suturing, using polyglycolic acid mesh as artificial pleura. METHODS:
      Forty-five patients undergoing video-assisted major pulmonary resection in our
      institute were enrolled in this study. Pneumostasis was done for intraoperative
      air leaks, by combining polyglycolic acid mesh with fibrin glue. We removed the
      chest tube the day after the air leaks stopped. RESULTS: Pneumostasis was done
      for intraoperative air leaks in 28 patients. The air leaks stopped immediately,
      allowing chest tube removal on postoperative day 1 in all but one patient whose
      air leak took 1 day longer to disappear. The time of chest tube drainage and the
      postoperative stay were similar in the patients with and those without
      intraoperative air leaks (mean 1.0 days vs 1.2 days and 6.8 days vs 7.1 days,
      respectively). The percentage of predicted forced expiratory volume in one second
      was significantly lower in patients with, than in those without, intraoperative
      air leaks (p < 0.05). CONCLUSIONS: We achieved sutureless pneumostasis using
      bioabsorbable artificial pleura during video-assisted major pulmonary resection.
      This method may contribute to reducing hospitalization, especially in patients
      with poor pulmonary function.

PMID- 18036901
TI  - Complications of silicone stent insertion in patients with expiratory central
      airway collapse.
AB  - BACKGROUND: Silicone stent insertion is an alternative treatment for expiratory
      central airway collapse. This study evaluates the complications (mucus plugging,
      migration, and granulation tissue) associated with stenting in patients who
      failed medical therapy and were not surgical candidates. METHODS: Chart review
      from 15 consecutive patients treated by silicone stent insertion was done over a
      2-year period. Outcomes included (1) changes in functional class, extent and
      severity of airway collapse (graded from 1 to 4 by using a multidimensional
      system), procedure- and stent-related complications at 48 hours after stent
      insertion; (2) frequency of stent-related complications; and (3) frequency of
      emergent flexible and rigid bronchoscopy (scheduled or emergent) over the follow
      up period. RESULTS: Mean functional class and severity and extent of airway
      collapse significantly improved within 48 hours after treatment (p < 0.05). There
      were no perioperative deaths. Stent-related complications within 48 hours after
      stent insertion occurred in 3 patients (1 granulation, 1 migration, and 1 mucus
      plugging). The mean duration of follow-up for the 12 patients who underwent
      clinical and bronchoscopic follow-up was 188 days. Twenty-six stent-related
      complications (12 mucus plugs, 8 migrations, and 6 granulation tissues) were seen
      in 10 of the 12 patients. Five emergent flexible bronchoscopies and 14 rigid
      bronchoscopies (6 of which were emergent) were performed during the follow-up
      period. CONCLUSIONS: Silicone stent insertion improves functional status
      immediately after intervention in patients with expiratory central airway
      collapse, but is associated with a high rate of stent-related complications and
      need for repeat bronchoscopic interventions.

PMID- 18036900
TI  - Two-year improvement in multidimensional body mass index, airflow obstruction,
      dyspnea, and exercise capacity index after nonresectional lung volume reduction
      surgery in awake patients.
AB  - BACKGROUND: This study analyzed the comprehensive 2-year outcome of
      nonresectional lung volume reduction surgery (LVRS) in awake patients, including
      calculation of the multidimensional BODE index (body mass index, degree of
      airflow obstruction assessed by spirometry, modified Medical Research Council
      dyspnea grade, and 6-minute walking distance), which has proved a useful
      predictor of survival in patients with chronic obstructive pulmonary disease.
      METHODS: The study cohort included 42 patients undergoing LVRS while awake within
      a staged bilateral program entailing unilateral LVRS, followed by contralateral
      treatment performed at the reappearance of disabling symptoms. Outcome measures
      included hospital stay, procedure-related costs, calculation of the
      multidimensional BODE index, actuarial survival, and freedom from contralateral
      LVRS. Results were compared with those of a control group undergoing resectional
      LVRS under general anesthesia. RESULTS: The groups were well matched in
      demographics and baseline measures. There was no operative mortality. Median
      hospital stay was significantly shorter in the awake group (6 days versus 9 days,
      p < 0.0001); median procedure-related costs were significantly lower in the awake
      group (euro5220 versus euro8580; p < 0.0001). At intergroup comparisons of awake
      versus control group of clinical results, the BODE index improved postoperatively
      in both groups (-2.24 +/- 1.0 versus -1.95 +/- 1.0, intergroup p = 0.35) and
      remained improved for up to 2 years (-1.95 +/- 1.3 versus -1.37 +/- 1.4,
      intergroup p = 0.1); 2-year survival and freedom from contralateral LVRS rates
      were 87% versus 91% (p = 0.52) and 74% versus 73% (p = 0.71), respectively.
      CONCLUSIONS: A significant improvement in the BODE index, satisfactory survival,
      and high rate of freedom from contralateral LVRS occurred both in the awake and
      control group, although the awake procedure proved more cost-effective.

PMID- 18036902
TI  - Atrial fibrillation after lung transplantation: timing, risk factors, and
      treatment.
AB  - BACKGROUND: Atrial fibrillation (AF) is common after lung transplantation and can
      be challenging to manage. Objectives of this study were to determine prevalence
      and timing of perioperative AF, identify its risk factors, evaluate treatment
      strategies, assess return to sinus rhythm by hospital discharge, and investigate
      its impact on outcomes. METHODS: From March 1995 to January 2005, 333 patients
      underwent primary lung transplantation (exclusive of heart and lung
      transplantation). Data on timing, prevalence, management, and outcome were
      extracted from the Unified Transplant Registry and Cardiothoracic Anesthesia
      databases, supplemented with medical record review. Risk factors for AF were
      identified by logistic regression analysis, and bootstrap bagging was used for
      variable selection. RESULTS: AF developed postoperatively in 68 patients (20%),
      with the peak incidence 2 days after operation. Risk factors were older age (p =
      0.0004), primary pulmonary hypertension (5 of 12 [42%] versus 63 of 321 [20%] for
      others, p = 0.006), and extremes of weight (p = 0.04). Pharmacologic treatment
      consisted of rate control agents only in 18 patients (27%), antiarrhythmics only
      in 5 (7.5%), and both in 44 (66%). Cardioversion was required in 24 (36%). Rhythm
      was recorded for 59 patients, and 55 (93%) were in sinus rhythm at discharge.
      Postoperative AF had no short-term or long-term survival impact. CONCLUSIONS: AF
      after lung transplantation is common, with occurrence peaking 2 days
      postoperatively. Older patients and those with primary pulmonary hypertension are
      at elevated risk. Treatment requires a combination of multiple pharmacologic
      agents and electrical cardioversion. Almost all patients are discharged in sinus
      rhythm, and prognosis is unaffected.

PMID- 18036903
TI  - Neurocognitive outcomes 3 years after coronary artery bypass graft surgery: a
      controlled study.
AB  - BACKGROUND: Cardiopulmonary bypass has been implicated in the late cognitive
      decline that has been reported after coronary artery bypass graft (CABG) surgery.
      Because most studies did not include a control group, a causal link of such
      decline with the use of cardiopulmonary bypass has not been established. METHODS:
      We compared changes in cognitive performance from baseline to 3 years in patients
      undergoing on-pump CABG (n = 152) with those of three control groups: patients
      with off-pump surgery (n = 75); with diagnosed coronary artery disease but no
      surgery (n = 99); and without coronary artery disease risk factors (n = 69).
      Neuropsychological performance was assessed by standardized tests of attention,
      language, verbal and visual memory, visuospatial, executive function, and
      psychomotor and motor speed. RESULTS: Relative to their baseline performance, no
      group had significantly lower performance at 36 months for any of the cognitive
      domains. From 12 to 36 months, there were no statistically significant
      differences in the degree of change between the on- and off-pump surgery groups.
      There was a trend toward mild decline in some cognitive domains, but overall
      differences among groups in degree of change over time were not statistically
      significant. CONCLUSIONS: We found a mild but nonsignificant trend toward late
      postoperative cognitive decline for all study groups with coronary artery
      disease, but no significant differences in the degree of late postoperative
      cognitive decline after on-pump compared with off-pump surgery. These findings
      suggest that previously reported late decline after bypass surgery is not
      specific to use of cardiopulmonary bypass.

PMID- 18036904
TI  - Neurocognitive outcomes of off-pump versus on-pump coronary artery bypass: a
      prospective randomized controlled trial.
AB  - BACKGROUND: Preliminary reports have documented the safety of off-pump coronary
      artery bypass graft compared with conventional coronary artery bypass graft
      surgery. Whereas off-pump coronary artery bypass graft surgery may be associated
      with improvement in some short-term outcomes, longer-term outcomes and influence
      on neurocognitive function have not been fully assessed. We examined short-term
      and intermediate-term neurocognitive and index admission morbidity and mortality
      after coronary artery bypass surgery performed with and without the use of
      extracorporeal circulation. METHODS: We prospectively randomly assigned 201
      patients undergoing nonemergent isolated coronary artery bypass graft surgery to
      conventional coronary artery bypass graft surgery (n = 102) or off-pump coronary
      artery bypass graft surgery (n = 99). The primary end points of the study were
      neurocognitive function assessed using a 19-test neurocognitive battery at
      baseline, discharge, and 6 months. Neurocognitive deficit was defined as a 20% or
      greater reduction from baseline in at least 20% of the tests. Secondary end
      points included index admission mortality, stroke, low-output cardiac failure,
      return to the operating room for bleeding, and postoperative troponin release.
      Risk ratios and 95% confidence intervals were calculated based on intention-to
      treat analysis. RESULTS: There was no difference in neurocognitive deficit at
      discharge (discharge versus preoperative: risk ratio, 0.83; 95% confidence
      interval, 0.65 to 1.07) or at 6 months (6 months versus preoperative: risk ratio,
      0.94; 95% confidence interval, 0.70 to 1.28). There was no significant difference
      in mortality or morbidity between the two groups. The off-pump coronary artery
      bypass graft group had fewer patients with troponin release than the conventional
      coronary artery bypass graft group. CONCLUSIONS: Off-pump coronary artery bypass
      graft surgery did not result in decreased frequency of neurocognitive deficit.
      Off-pump coronary artery bypass graft surgery was associated with substantially
      lower levels of troponin release after surgery.

PMID- 18036905
TI  - Long-term survival after surgery versus percutaneous intervention in
      octogenarians with multivessel coronary disease.
AB  - BACKGROUND: There is limited information comparing long-term survival after
      percutaneous coronary intervention (PCI) versus coronary artery bypass grafting
      (CABG) in patients aged 80 years and older. We studied the long-term survival of
      octogenarians with multivessel coronary artery disease undergoing PCI or CABG who
      might have been candidates for either procedure. METHODS: We identified 1693
      patients, aged 80 to 89, with two-vessel disease (57.6%) or three-vessel disease
      (42.4%), without left main disease, undergoing a first, nonemergency
      revascularization from 1992 to 2001. Adjusted hazard ratios (HR) were calculated
      for CABG versus PCI. Because survival curves for these procedures crossed midway
      through year 1, results were analyzed separately for the first 6 months and 6
      months to 8 years. RESULTS: PCI was performed in 54.6% of patients with two
      vessel disease and 23.7% of those with three-vessel disease. More CABG patients
      were men (54.7% versus 43.3%). The CABG patients had more peripheral vascular
      disease (23.1% versus 15.2%) and congestive heart failure (24.5% versus 13.1%)
      but less renal failure (4.6% versus 9.1%) and fewer prior myocardial infarctions
      (48.7% versus 53.6%). In-hospital mortality was 3.0% for PCI and 5.9% for CABG (p
      = 0.005). CABG was associated with poorer survival than PCI during the first 6
      months (HR, 1.32; p = 0.135). Survival from 6 months to 8 years was significantly
      better with CABG for the group as a whole (HR, 0.72; p = 0.005) and for patients
      with two-vessel disease (HR, 0.68; p = 0.016), and there was a nonsignificant
      trend for those with three-vessel disease (HR, 0.75; p = 0.177). CONCLUSIONS:
      Patients aged 80 years or older with multivessel disease must consider the trade
      off between the increased early risks of CABG in return for improved long-term
      survival.

PMID- 18036906
TI  - Hospital outcome analysis after different techniques of left internal mammary
      grafts harvesting.
AB  - BACKGROUND: Although accepted worldwide as the first-choice conduit for
      myocardial revascularization (coronary artery bypass graft surgery), it is still
      questionable if left internal mammary arteries (LIMAs) do better as pedicled or
      skeletonized grafts. Recent reports have suggested that the skeletonized
      technique improves the outcomes. METHODS: In all, 516 consecutive isolated
      coronary artery bypass graft surgery patients admitted between January 2003 and
      February 2007 were grouped according to the harvesting technique of LIMAs (387
      pedicled versus 129 skeletonized). Intraoperative transit time flow results,
      hospital outcome, perioperative troponin I leakage, and echocardiographic results
      were analyzed. Maximum, mean, and minimum flows, pulsatility index, and graft
      flow reserve were stratified according to the type of surgery (on pump and off
      pump) and subgroups at risk (severe left ventricular hypertrophy). RESULTS: The
      transit time flow results were unsatisfactory in 4 patients (0.8%), all 4 of whom
      underwent redo anastomosis. Maximum, mean, and minimum flows and pulsatility
      index values were comparable between skeletonized and pedicled LIMAs (p = not
      significant), for both on-pump and off-pump surgeries (p = not significant).
      Graft flow reserve was comparable between the two groups (p = not significant),
      as well as transit time flow results in severe ventricular hypertrophy. Troponin
      leakage, postoperative echocardiographic recovery, and hospital outcome were
      comparable between the two groups (p = not significant at all time points). Only
      superficial wound complications proved higher in the pedicled group (2.6% versus
      skeletonized group: 0%; p = 0.05). CONCLUSIONS: Pedicled LIMA carries a higher
      risk for minor wound complications. Neverthless, the two techniques showed
      similar in-vivo functional behavior and hospital outcome. Therefore, there is no
      reason to prefer one technique over the other.

PMID- 18036907
TI  - Myocardial protection during elective coronary artery bypass grafting using high
      dose insulin therapy.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) with cardioplegic cardiac
      arrest and cardiopulmonary bypass (CPB) is associated with myocardial injury. The
      aim of this study was to investigate whether high-dose insulin therapy has a
      myocardial protective effect by enhancing early metabolic recovery of the
      arrested heart during revascularization. METHODS: A total of 44 patients
      undergoing elective CABG were randomized to receive intraoperative titrated
      intravenous insulin infusion (n = 22) or a fixed high-dose systemic insulin
      infusion at 5 mU/kg/min (n = 22). Blood samples were collected simultaneously
      from the radial artery and the coronary sinus before starting CPB and at 5 and 10
      minutes after the release of the aortic cross-clamp to determine lactate, oxygen
      saturation, and hemoglobin concentration. Lactate extraction/excretion and
      myocardial oxygen extraction were calculated and compared between the two groups.
      The change in cardiac indices was determined immediately postoperatively as a
      measure of functional recovery, and the troponin I level was measured 4 hours
      postoperatively as an indicator of myocardial protection. RESULTS: Operative
      characteristics, including CPB and aortic cross-clamp time, were similar between
      the two groups. Arterial oxygen content was similar in both groups. The high-dose
      insulin therapy group had early extraction of lactate and higher oxygen
      extraction immediately postoperatively compared with the standard group. In
      addition, the high-dose insulin group had a lower troponin I level 4 hours
      postoperatively, with greater improvement in cardiac indices. CONCLUSIONS: High
      dose insulin therapy promotes early metabolic recovery of the heart during
      elective CABG, leading to better myocardial protection and functional recovery.

PMID- 18036908
TI  - Predicting early coronary artery bypass graft failure by intraoperative transit
      time flow measurement.
AB  - BACKGROUND: A primary limitation of using transit time flow measurement to
      predict early graft failure in coronary artery bypass grafting has been the lack
      of cutoff values for objective criteria. METHODS: We analyzed a total of 261
      grafts that were evaluated by intraoperative transit time flow measurement and
      underwent early postoperative coronary angiography within 3 months of surgery.
      Based on the control angiography, failing grafts were defined as occluded or
      patent grafts with greater than 50% stenosis or poor flow characteristics. Normal
      and failing graft indicators were compared according to the graft territories.
      RESULTS: According to the receiver operating characteristic curve analysis for
      the grafts to left coronary arteries, a mean flow of 15 mL/min or less, a
      pulsatility index of 5.1 or higher, and a backward flow of 4.1% or higher were
      found to be the optimal cutoff criteria to predict early graft failure.
      Similarly, for the grafts to right coronary arteries, the cutoff values were 20
      mL/min, 4.7, and 4.6%, respectively. A systolic dominant flow curve pattern was a
      risk factor only in grafts to the left coronary arteries. Negative predictive
      values of these cutoff criteria ranged from 0.91 to 0.96, whereas positive
      predictive values ranged from 0.31 to 0.80. CONCLUSIONS: Using these criteria,
      transit time flow measurement may be a useful method to predict early graft
      failure. However, surgeons should be aware of the low positive predictive values
      to avoid unnecessary graft revision.

PMID- 18036909
TI  - Invited commentary. Coronary artery bypass grafting (CABG) ideally mandates the
      use of objective technology to confirm graft patency.

PMID- 18036910
TI  - Surgical treatment of active aortic endocarditis: homografts are not the
      cornerstone of outcome.
AB  - BACKGROUND: Surgical treatment of active aortic infective endocarditis is
      challenging, and the type of prosthesis to be implanted during the active phase
      remains controversial. METHODS: All consecutive patients with definite diagnosis
      of aortic infective endocarditis operated on during the active phase were
      included. Endpoints were in-hospital mortality and a combined endpoint including
      infective endocarditis recurrence, prostheses dysfunction, or long-term
      cardiovascular mortality. RESULTS: Among 127 consecutive patients, mean age 57 +/
      15 years, 87% male, 30% with preexisting aortic prosthesis, and 63 (50%) with
      annulus abscess, 54 (43%) were treated with aortic homograft and 73 (57%) with
      conventional prosthesis. Median time between diagnosis and surgery was 10 days.
      In-hospital mortality was 9%, not different between homograft and conventional
      prostheses (11% versus 8%, p[ = 0.6). By multivariable analysis, prosthetic valve
      endocarditis (8.5 95% confidence interval: 2.2 to 33.6, ]p = 0.001) was the only
      variable independently associated with in-hospital mortality, which was not
      influenced by type valvular substitute (p = 0.6), even in the subset with annulus
      abscess (p = 0.2). Ten-year survival free from the combined endpoint was 44% +/-
      10%, not different between homograft and conventional prostheses (log rank p =
      0.2). By multivariable analysis, comorbidity index (2.6 [1.05 to 6.3], p = 0.04)
      and prosthetic valve endocarditis (2.3 [1.2 to 4.6], p = 0.02) were independently
      predictive of the combined endpoint, which was not determined by type of valvular
      substitute (p = 0.6) even in the subset with annulus abscess (p = 0.5).
      CONCLUSIONS: Implantation of conventional prostheses during the active phase of
      aortic endocarditis yields similar low operative mortality and long-term
      prognosis as compared with aortic homografts, even in patients with annulus
      abscess.

PMID- 18036911
TI  - Invited commentary. It would not be wise to completely abandon the use of
      homograft root replacement in particular in patients with prosthetic valve
      endocarditis and aortic root abscess.

PMID- 18036912
TI  - Midterm follow-up of tricuspid valve reconstruction due to active infective
      endocarditis.
AB  - BACKGROUND: Surgical methods for treatment of tricuspid valve (TV) endocarditis
      include complete TV excision, TV replacement, and the use of various
      reconstructive techniques even in cases of severe TV destruction and
      incompetence. This study summarizes our experience with TV reconstruction and
      replacement in patients with severe TV endocarditis. METHODS: Between October
      1997 and July 2004, TV reconstruction was performed in 18 patients (mean age, 38
      +/- 17 years; 7 women, 11 men), and TV replacement in 4 patients (mean age, 48 +/
      22 years; 2 women, 2 men). All patients presented with active endocarditis and
      severe TV incompetence. Reconstructive techniques included debridement of
      vegetations, complete resection of infected or destroyed leaflet tissue, leaflet
      reconstruction with pericardial tissue, sliding plasty of residual valve tissue
      and bicuspid valve formation with construction of a new commissure, and
      consecutive ring annuloplasty in all patients. RESULTS: There were no
      perioperative deaths. Late mortality was 0% for patients with TV reconstruction
      and 25% (n = 1) in the TV replacement group. At the latest follow-up (78%
      complete; mean, 53 +/- 18 months), 11 patients had no recurrent TV incompetence.
      Three patients presented with TV incompetence grade I or II. Two patients with TV
      reconstruction had recurrent TV endocarditis between 3 and 18 month
      postoperatively, including new vegetations in both patients and an additional
      pleural empyema in one. In all cases, conservative treatment was successful and
      no reoperation was required. CONCLUSIONS: The results of our study clearly
      demonstrate that in patients with severe TV endocarditis, complex reconstructive
      techniques yield excellent midterm results with regard to freedom of recurrence
      of endocarditis and valvular competence and should be considered as the primary
      surgical option in these patients. Tricuspid valve replacement should only be
      performed in cases of severe TV destruction that renders reconstructive
      techniques impossible.

PMID- 18036913
TI  - Invited commentary. An outstanding series of tricuspid valve operations for
      infective endocarditis.

PMID- 18036914
TI  - Surgical management of aortic regurgitation associated with takayasu arteritis
      and other forms of aortitis.
AB  - BACKGROUND: Surgical management of aortic regurgitation associated with aortitis
      can be complicated with occurrence of prosthetic valve detachment or formation of
      pseudoaneurysm at the suture line. Postoperative morbidity includes progressive
      dilatation of the aortic root. We sought to assess our midterm and long-term
      results of surgical management of aortic regurgitation associated with aortitis.
      METHODS: Between January 1989 and September 2004, 15 patients (17 cases) with
      aortic regurgitation caused by aortitis were surgically treated. Of 17 cases, 6
      cases had aortic valve replacement and 11 cases had aortic root replacement. All
      the patients were followed up from 3 months to 15 years with a mean follow-up
      period of 70.8 +/- 54.9 months. RESULTS: There was no hospital death in all the
      procedures. During the follow-up period, 1 patient died of prosthetic valve
      detachment, and 2 patients required aortic root replacement for prosthetic valve
      detachment or aortic root dilatation after aortic valve replacement, whereas
      there was neither cardiac death nor reoperation after aortic root replacement.
      CONCLUSIONS: Low operative mortality and favorable long-term outcome may justify
      lowering the threshold toward aortic root replacement for aortic regurgitation
      with aortitis in view of the propensity for development of prosthetic valve
      detachment.

PMID- 18036915
TI  - Invited commentary. Regurgitation develops primarily as a result of annular
      dilatation resulting from enlargement of the ascending aorta.

PMID- 18036916
TI  - Fate of the residual distal and proximal aorta after acute type a dissection
      repair using a contemporary surgical reconstruction algorithm.
AB  - BACKGROUND: In this study, we evaluated the long-term results of our
      contemporary, standardized surgical management algorithm for repair of acute type
      A aortic dissections. Prior reports have analyzed heterogeneous techniques and
      populations. METHODS: From 1993 to 2004, 221 consecutive patients underwent
      repair of acute type A aortic dissection at our aortic center. Hemiarch repair
      was performed in 97.7% (216 of 221), and total arch in 2.3% (5 of 221). Of these,
      72.9% (161 of 221) underwent aortic valve resuspension, and 27.1% (60 of 221) had
      aortic root replacement. RESULTS: In-hospital mortality for a primary operation
      was 12.7% (28 of 221). Actuarial survival was 79.2% at 1 year, 62.8% at 5 years,
      and 46.3% at 10 years. Significant risk factors for decreased survival included
      prior stroke, cerebral malperfusion, and length of cardiopulmonary bypass.
      Freedom from proximal reoperation after aortic valve resuspension was 94.6% at 5
      years and 76.8% at 10 years, with cardiac malperfusion as the main risk factor.
      Freedom from distal reoperation was 87.6% at 5 years and 76.4% at 10 years, with
      Marfan syndrome, age, and extent of dissection as significant risk factors for
      reoperation. In-hospital mortality was 18.2% (2 of 11) after proximal reoperation
      and 31.2% (5 of 16) after distal reoperation. CONCLUSIONS: We report improved
      long-term durability of our proximal root repair, with cardiac malperfusion as a
      significant risk factor. Marfan disease, younger age, and DeBakey type I
      dissection are risk factors for distal reoperation. To further improve long-term
      outcome, means to prevent progression of distal aortic disease need to be
      developed.

PMID- 18036917
TI  - Endovascular versus open repair for blunt thoracic aortic injury: short-term
      results.
AB  - BACKGROUND: Endovascular stent grafting has been increasingly used as an
      alternative treatment modality. The aim of this study is to evaluate the
      immediate and short-term results of endovascular stent grafting repair after
      blunt thoracic aortic injury due to trauma. METHODS: A review of a tertiary
      trauma center registry identified all patients who suffered blunt thoracic aortic
      injury from 2002 to 2006. All patients underwent either open repair with
      synthetic graft interposition or endovascular stent grafting (EVS) of the
      descending thoracic aorta. Type and severity of injury, concomitant injuries,
      clinical factors, and outcome were compared between groups. Univariate and
      multivariate analysis was performed. RESULTS: Endovascular stent grafting was
      performed in 22 patients, and 10 patients underwent open surgical repair. In the
      open group, the 30-day mortality rate was 10%, the paraplegia rate was 10%, and
      incidence of major complications was 30%, which were comparable with the
      incidences observed in the EVS group of 4.5%, 4.5%, and 13.6%, respectively. No
      statistically significant differences were demonstrated. Multivariate regression
      analysis identified associated thoracic injury as the main independent predictor
      of hospital length of stay (p = 0.03, 95% confidence interval: 0.53 to 18.85). In
      the EVS group, 1 patient died in the short-term follow-up period and 2 cases of
      endovascular leak required additional treatment. CONCLUSIONS: Although
      postoperative mortality and morbidity between open and endovascular repair were
      comparable, EVS can be considered a safe alternative treatment modality in the
      therapeutic algorithm of blunt thoracic aortic injury particularly for the higher
      risk multitrauma patients.

PMID- 18036918
TI  - Combined surgical and endovascular repair of complex aortic pathologies with a
      new hybrid prosthesis.
AB  - BACKGROUND: We evaluated the application of a new combined surgical and
      endovascular technique for the treatment of thoracic aortic aneurysms and
      dissections. The technique is used to treat extensive aortic disease by a single
      stage procedure. Surgical outcomes and follow-up data are summarized and
      analyzed. METHODS: Between August 2005 and December 2006, 7 patients (2 women),
      aged 62 +/- 11 years, with aortic pathologies (5 dissections, 2 aneurysms)
      underwent replacement of the ascending aorta and the aortic arch and simultaneous
      stent graft implantation into the descending aorta. The stent graft used was the
      E-vita open endoluminal stent graft (Jotec Inc, Hechingen, Germany), which was
      implanted using the technique of circulatory arrest and moderate hypothermia with
      selective antegrade cerebral perfusion. The stent graft was deployed under visual
      guidance through the open aortic arch into the true lumen. RESULTS:
      Intraoperative antegrade stenting of the descending aorta combined with the
      distal ascending aorta and aortic arch repair was performed successfully in all
      patients. The survival rate was 100%. One patient had a postoperative neurologic
      deficit but recovered completely. Four patients had fully thrombosed perigraft
      spaces within 11 days, whereas 1 patient showed complete obliteration of the
      false lumen at the 3-month control. CONCLUSIONS: The combined surgical and
      endovascular technique described in this report proved feasible for the treatment
      of extended aortic lesions. It serves as an additional option for aortic repair
      in a single-stage method and is associated with no elevated risk for the patient.

PMID- 18036919
TI  - Invited commentary. Primary or reoperative surgery of the thoracic aorta
      continues to be a challenge.

PMID- 18036920
TI  - Ultrasonic cardiac ablation for atrial fibrillation during concomitant cardiac
      surgery: long-term clinical outcomes.
AB  - BACKGROUND: Therapeutic ultrasound as an alternative to the maze procedure was
      evaluated in this large US experience. Safety and efficacy were assessed at 6-,
      12-, and 18-month visits with systematic 24-hour Holter monitoring. METHODS: From
      February 2005 to February 2007, 220 patients were prospectively enrolled in a
      single center study, and among them 129 patients with concomitant cardiac surgery
      and at least 6-month follow-up were reviewed. Primary procedures were mitral
      surgery in 50% of the cases, coronary bypass in 32%, and aortic surgery in 16%.
      Atrial fibrillation was permanent in 66 (51.1%), paroxysmal in 43 (33.3%), and
      persistent in 20 (15.5%) patients. An epicardial and circumferential left atrial
      encircling line was created on the beating heart. Routinely a mitral isthmus line
      was also created from the left atrium epicardium using an ultrasonic handheld
      device. RESULTS: No morbidity or mortality was device-related. There were four
      (2.33%) early deaths and six late extra-cardiac deaths. Follow-up ranged from 6
      to 670 days with a mean follow-up of 358.5 days, median 340 days with two
      patients lost to follow-up. Freedom from atrial fibrillation or left-sided
      flutter was 83.2%, 84.4%, and 86.2% at 6, 12, and 18 months, respectively. A
      pacemaker was implanted in seven patients (5.4%). Male gender and left atrial
      dimension were significant risk factors for failure. CONCLUSIONS: The study
      confirms the excellent safety record of the technology, and the efficacy at the
      level reported in a previous European multicenter study. Efficacy is also
      maintained at longer (12 and 18 months) follow-up.

PMID- 18036921
TI  - Tracheostomy is not a risk factor for deep sternal wound infection after cardiac
      surgery.
AB  - BACKGROUND: Previous studies on predictors of deep sternal wound infection (DSWI)
      have identified either respiratory failure or tracheostomy as a risk factor for
      the occurrence of this complication. This study was conducted to analyze the
      interaction between these two variables. We hypothesize that respiratory failure
      and not tracheostomy per se is associated with an increased risk of DSWI.
      METHODS: We analyzed 2823 patients who underwent cardiac operations through
      median sternotomy between January 2002 and September 2006. Patients were divided
      into three groups: respiratory failure with or without tracheostomy (tracheostomy
      versus nontracheostomy) and patients without respiratory failure. The primary
      outcome measure was the incidence of DSWI in each group and its predictors.
      RESULTS: Postoperative respiratory failure was observed in 252 patients (9%): 144
      without tracheostomy (57%) and 108 with tracheostomy (43%). The mean duration of
      intubation in nontracheostomy patients was 19 +/- 12 days. The mean duration to
      tracheostomy was 13 +/- 6 days. DSWI occurred in 38 patients (1.3%): patients
      with no respiratory failure, 1%; patients with respiratory failure, 5.1% (p <
      0.001). The incidence of DSWI was similar between tracheostomy (4.6%) and
      nontracheostomy patients (5.6%, p = 0.5). The mean time to diagnosis of DSWI was
      25 +/- 14 days and was similar for all groups. The mean number of days to
      tracheostomy was 12 +/- 3 days in DSWI patients and 13 +/- 6 in patients without
      DSWI (p = 0.7). In multivariate analysis, respiratory failure was the strongest
      predictor of DSWI (odds ratio, 5.2). Tracheostomy was not identified as a
      predictor of DSWI or hospital mortality. CONCLUSIONS: The incidence of DSWI
      remains high in patients with respiratory failure. Tracheostomy is not a risk
      factor for DSWI and serves as a surrogate for respiratory failure. Therefore,
      considering that early tracheostomy may be beneficial in patients with
      respiratory insufficiency, a more liberal approach to early tracheostomy may be
      warranted.

PMID- 18036922
TI  - Invited commentary. Respiratory failure should be managed aggressively and a
      tracheostomy should not be withheld once the need for prolonged ventilatory
      support has been established.

PMID- 18036923
TI  - Feasibility study of a temporary percutaneous left ventricular assist device in
      cardiac surgery.
AB  - BACKGROUND: The aim of this study is to evaluate a percutaneous left ventricular
      assist device (Tandem Heart pVAD; Cardiac Assist, Pittsburgh, Pennsylvania) in
      the postcardiotomy setting. METHODS: Between August 2001 and August 2004, 11 high
      risk male patients who had undergone heart failure surgery or surgical
      revascularization were supported by the TandemHeart postcardiotomy. The major
      indication for pVAD insertion was failure to wean from cardiopulmonary bypass.
      Three different techniques were employed for cannulation: the closed percutaneous
      technique, the "open transeptal" technique with percutaneous cannulas insertion,
      and direct central cannulation. RESULTS: The mean duration of support was 88
      hours. The mean pump flow was 3.09 L/min. The weaning rate was 72.72%. Survival
      to discharge and at 1 and 4 years was 54.54%, 45.45%, and 36.36%, respectively.
      The main complication was pericardial bleeding, noted mainly in patients
      receiving antiplatelet treatment preoperatively. CONCLUSIONS: The TandemHeart
      appears to be safe for temporary support after cardiotomy. It is a versatile
      device allowing different techniques of insertion. Device application yielded
      high weaning rate and satisfactory early and long-term survival.

PMID- 18036924
TI  - Extracorporeal circulation activates endothelial nitric oxide synthase in
      erythrocytes.
AB  - BACKGROUND: Extracorporeal circulation used in cardiopulmonary bypass and
      hemodialysis is often associated with severe hypotension, which is an important
      predictor for mortality and morbidity. One pathophysiological hypothesis includes
      nitric oxide (NO) generation. Recently, a functional NO synthase (endothelial
      type NO synthase [eNOS]), was found to be expressed in human red blood cells.
      However, to date, activation of red blood cell eNOS has not been shown. We
      hypothesized that eNOS in circulating red blood cells might be activated during
      extracorporeal circulation and thus contribute to hypotension through
      vasodilation upon NO release. METHODS: We collected blood samples from 28
      patients electively subjected to cardiac surgery during cardiopulmonary bypass
      (0, 20, 40, 60, and 80 minutes of cardiopulmonary bypass; taken for routine blood
      gas analyses). Red blood cells were immunohistochemically stained against
      activated eNOS. The degree of activation was assessed by television densitometry
      (gray units). RESULTS: We found significant red blood cell eNOS activation during
      cardiopulmonary bypass in a time dependent fashion. The eNOS activation occurred
      by dissociation of the enzyme from the cellular membrane into the cytosol
      (translocation). The correlation between activated eNOS and bypass duration was
      highly significant. CONCLUSIONS: Red blood cells might contribute to hypotension
      through vasodilation upon NO release during extracorporeal circulation and could
      serve as new therapeutic targets in clinical practice.

PMID- 18036925
TI  - Ventricular restraint prevents infarct expansion and improves borderzone function
      after myocardial infarction: a study using magnetic resonance imaging, three
      dimensional surface modeling, and myocardial tagging.
AB  - BACKGROUND: Infarct expansion is associated with impaired borderzone function,
      adverse remodeling, and poor long-term prognosis. We hypothesized that left
      ventricular restraint early after myocardial infarction limits infarct expansion,
      preserves borderzone function, and reduces remodeling. METHODS: We used an ovine
      model as well as high spatial and temporal resolution cardiac magnetic resonance
      imaging to quantify total and infarcted left ventricular epicardial surface area
      at baseline and 1 week and 12 weeks after anterior wall infarction in 10 animals.
      Five animals were randomly assigned to treatment with left ventricular restraint
      (Acorn cardiac support device) 1 week after infarction. Five animals were
      untreated controls. Total left ventricular surface area was measured by importing
      the end-diastolic magnetic resonance imaging-derived epicardial contours into
      custom software, which creates a three-dimensional surface from the two
      dimensional magnetic resonance imaging contours. Infarct area was calculated from
      magnetic resonance imaging-detectable titanium markers placed at the infarct
      border. Borderzone radial and circumferential strains during systole were also
      assessed using myocardial tagging techniques as a measure of contractile
      function. RESULTS: The infarct area 1 week after infarction was 1,177 +/- 386
      mm(2) in the control group and 1,124 +/- 427 mm(2) in the cardiac support device
      group. After 12 weeks, infarct area was 3,666 +/- 1,013 mm(2) in the control
      group and 1,227 +/- 301 mm(2) in the cardiac support device group. Borderzone
      systolic radial strain decreased from 12.6% +/- 0.77% to 3.6% +/- 0.3% after
      infarction in the control group and 13.7% +/- 0.87% to 4.7% +/- 0.3% in the
      cardiac support device group. At 12 weeks after infarction, radial strain was
      3.4% +/- 0.5% in the control group and 6.7% +/- 0.4% in the cardiac support
      device group. CONCLUSIONS: Early postinfarction left ventricular restraint limits
      infarct expansion and improves borderzone contractile function.

PMID- 18036926
TI  - Invited commentary. Myocardial infarction leads to both immediate and delayed
      morbidity and mortality.

PMID- 18036927
TI  - Simvastatin suppresses lung inflammatory response in a rat cardiopulmonary bypass
      model.
AB  - BACKGROUND: Inflammatory response in the lungs is a well-known complication after
      cardiopulmonary bypass (CPB). The main aims of our study were to explore whether
      pretreatment with simvastatin would inhibit toll-like receptor 4 expression and
      suppress lung inflammatory response in a rat CPB model. METHODS: Male Sprague
      Dawley rats were divided into four groups (n = 6 each): sham group; CPB (control
      group); CPB plus low-dose simvastatin (5 mg/kg daily [L-Sim group]); and CPB plus
      high-dose simvastatin (10 mg/kg daily [H-Sim group]). Blood samples were
      collected at the beginning and at the termination of CPB, and at 1, 2, 4, and 24
      hours after operation. The bronchoalveolar lavage fluid and lungs were harvested
      24 hours postoperatively. RESULTS: The simvastatin-treated groups had
      significantly higher ratios of PaO(2)/FiO(2) and lower values of respiratory
      index than the control group. We observed that simvastatin reduced CPB-induced
      toll-like receptor 4 and nuclear factor-kappaB expressions in CPB groups (p <
      0.01, versus control group). The levels of interleukin-6, tumor necrosis factor
      alpha, and monocyte chemotactic protein-1 in serum, bronchoalveolar lavage fluid,
      and lung tissues increased in CPB groups, whereas pretreatment with simvastatins
      reduced these inflammatory marks in a dose-dependent manner (p < 0.01, versus
      control group). Furthermore, pretreatment with simvastatin had a lower lung
      injury score (p < 0.05, versus control group). CONCLUSIONS: These findings
      suggest that simvastatin inhibited CPB-induced toll-like receptor 4 upregulation
      and nuclear factor-kappaB activation, efficaciously reduing the pulmonary
      inflammatory response after CPB.

PMID- 18036928
TI  - Invited commentary. New evidence regarding statins as antiinflammatory agents in
      the context of ECC.

PMID- 18036929
TI  - Outcomes after surgical treatment of children with partial anomalous pulmonary
      venous connection.
AB  - BACKGROUND: We explore early results and time-related morbidity after surgical
      repair of partial anomalous pulmonary venous connection (PAPVC) at our
      institution. METHODS: Between 1982 and 2006, 306 consecutive patients underwent
      surgery for PAPVC; of these, 236 (77%) were children with a median age of 5.3
      years (range, 0.47 to 18 years). Clinical and echocardiographic follow-up was
      obtained. RESULTS: PAPVC was right-sided in 214 patients (90%), left-sided in 17
      (7%), and bilateral in 5 (2%). Anomalous veins were partial in 186 patients (79%)
      and involved the entire lung in 50 (21%). The most common type was right PAPVC
      into the superior vena cava in 175 (74%), with 87% associated with sinus-venosus
      atrial septal defect; followed by right PAPVC into the right atrium in 29 (12%),
      left PAPVC into the innominate vein in 22 (9%), and scimitar syndrome in 15 (6%).
      Repair strategy included intracardiac baffle in 203, pulmonary vein implantation
      in 22, and SVC division with reimplantation on the right atrial appendage in 14.
      There was no early or late mortality. Freedom from reoperation, vena cava
      obstruction, pulmonary vein obstruction, and pacemaker implantation at 15 years
      was 97%, 97.8%, 86%, and 99.1%, respectively. Pulmonary vein obstruction was
      significantly more common in patients with scimitar compared with others (22.4%
      versus 98.3%, p < 0.0001). Postoperative quantitative lung perfusion scans in 13
      of 15 scimitar patients showed decreased right lung perfusion (mean, 22.5%).
      CONCLUSIONS: Surgical treatment of PAPVC is associated with excellent outcomes
      and low time-related morbidity. However, management of children with scimitar
      syndrome is complicated by an exceptionally high incidence of postoperative
      pulmonary venous obstruction and abnormally diminished perfusion of the right
      lung.

PMID- 18036930
TI  - Accuracy of the aristotle basic complexity score for classifying the mortality
      and morbidity potential of congenital heart surgery operations.
AB  - BACKGROUND: The Aristotle Basic Complexity Score (ABC score) was derived by
      consensus of an international surgeon panel to facilitate assessment of surgical
      performance for quality improvement in congenital heart surgery. The utility of
      the ABC score depends on its ability to correctly classify procedures according
      to their potential for morbidity, mortality, and technical difficulty. This
      collaborative study combined two multiinstitution databases to assess how well
      the ABC score predicts the actual morbidity and mortality potential of 131
      congenital heart surgery procedures. METHODS: Data from the European Association
      of Cardiothoracic Surgery (EACTS) congenital database (17,838 operations, 56
      centers) and the Society of Thoracic Surgeons (STS) congenital database (18,024
      operations, 32 centers) were analyzed. Discrimination of the ABC score for
      predicting in-hospital mortality and postoperative length of stay (PLOS) of more
      than 21 days was quantified by the C statistic. Procedure-specific rates of
      mortality and prolonged PLOS were compared with predictions from a logistic
      regression model, and an exact binomial test was used to identify procedures that
      were mortality and morbidity outliers. RESULTS: There was a significant positive
      correlation between the ABC score of a procedure and its observed procedure
      specific risk of mortality (C = 0.70) and prolonged PLOS (C = 0.67). Several
      individual procedures were identifed as mortality and morbidity outliers.
      CONCLUSIONS: The ABC score generally discriminates between low-risk and high-risk
      congenital procedures making it a potentially useful covariate for case-mix
      adjustment in congenital heart surgery outcomes analysis. Planned revisions of
      the ABC score will incorporate empirical data and will benefit from the large
      sample sizes of the STS and EACTS databases.

PMID- 18036931
TI  - Complete atrioventricular canal: comparison of modified single-patch technique
      with two-patch technique.
AB  - BACKGROUND: The purpose of this study was to compare the modified single-patch
      technique to the two-patch technique for infants with complete atrioventricular
      canal (CAVC) defects. METHODS: Between January 2000 and June 2006, 55 infants
      underwent CAVC repair. Twenty-six patients had a modified single-patch technique;
      29 patients had a two-patch technique. Trisomy 21 was present in 23 of 26 and 26
      of 29 patients (p = not significant [ns]). Mean age was 4.4 +/- 1.3 months
      (single-patch) versus 5.5 +/- 1.9 months (two-patch, p < 0.02). Mean weight was
      4.74 +/- 0.92 versus 5.28 +/- 1.67 kilograms (p = ns). RESULTS: There was one
      death in the modified single-patch group (postoperative day 130, liver failure)
      and no deaths in the two-patch group. Cross-clamp times and cardiopulmonary
      bypass times were shorter in the modified single-patch group (97.3 +/- 19.9 vs
      123.3 +/- 28.2 minutes, p < 0.0003; 128 +/- 25 vs 157 +/- 37, p < 0.03). Rastelli
      classification was type A (18 vs 14), B (1 vs 0), and C (7 vs 15). Mean size of
      the ventricular septal defect as assessed by transesophageal echocardiogram was 9
      +/- 2 mm, (single-patch) versus 10 +/- 3 mm (two-patch) (p = ns). Median
      postoperative length of stay did not differ (10 vs 8 days). There was no
      difference in the degree of postoperative left or right AV valve insufficiency as
      assessed by serial echocardiography. One patient (4%) required reoperation for
      mitral insufficiency in the modified single-patch versus three patients in the
      two-patch group (10%, p = ns). There were no patients with third degree
      atrioventricular block or that required reoperation for residual VSD in the
      modified single-patch group. There was one patient with third-degree AV block
      that required a pacemaker and one patient who had reoperation for a residual
      ventricular septal defect in the two-patch group (p = ns). No patient in either
      group required reoperation for left ventricular outflow tract obstruction.
      CONCLUSIONS: The modified single-patch technique produced results comparable with
      the two-patch technique in younger patients with similarly sized ventricular
      septal defects. Furthermore, the modified single-patch technique was performed
      with significantly shorter cross-clamp and cardiopulmonary bypass times.

PMID- 18036932
TI  - Follow-up of Shelhigh porcine pulmonic valve conduits.
AB  - BACKGROUND: We implanted Shelhigh porcine pulmonic valve conduits because of the
      limited availability of homografts in our country. The aim of this study was to
      evaluate the short-term results of SPVC. METHODS: From November 2002 to July
      2005, the Shelhigh porcine pulmonic valve conduit was implanted in 73 patients
      (81 procedures) in the right ventricular outflow tract to correct congenital
      heart diseases. Operative procedures were Rastelli operation in 65, anatomic
      correction of atrioventricular discordance in 5, and Ross operation in 3. Age at
      operation was 6.8 +/- 7.5 years, including 11 patients under 1 year. The median
      conduit size was 18 mm (range, 12 to 24 mm). RESULTS: There was no operative
      mortality and 1 nonconduit-related late death (mean follow-up, 11.3 +/- 10.7
      months). Ten conduits (12.3%, 7 patients) were removed at a median of 9.6 months
      (range, 2.5 to 25.4) owing to obstruction in 9 and pseudoaneurysm in 1. In the
      explanted conduits, we found a prominent intimal peel at the distal anastomosis
      without leaflet calcification. Freedom from reoperation at 24 months was 87% +/-
      11.7% in large-sized conduits (>or=18 mm) and 62.8% +/- 10.6% in small-sized
      conduits (<or=16 mm). Especially, 12-mm sized conduit showed 33.3% freedom from
      reoperation during the first 12 months of follow-up. CONCLUSIONS: On the basis of
      our short-term results, Shelhigh porcine pulmonic valve conduits are not
      satisfactory. Small-sized conduits (<or=16 mm) fail earlier; large-sized conduits
      (>or=18 mm) fail after 2 years of implantation due to intimal peel formation at
      the distal segment.

PMID- 18036933
TI  - Invited commentary. Favorable early and mid-term outcomes after corrective
      congenital surgery (including reconstruction of the right ventricular outflow
      tract) have led to an increasing demand for right ventricular-pulmonary artery.

PMID- 18036934
TI  - Hyperglycemia after infant cardiac surgery does not adversely impact
      neurodevelopmental outcome.
AB  - BACKGROUND: Hyperglycemia has been associated with worse outcome after traumatic
      brain injury and cardiac surgery in adults. It is not known whether postoperative
      hyperglycemia results in worse neurodevelopmental outcome after infant cardiac
      surgery. METHODS: Secondary analysis of postoperative glucose levels was
      performed in infants younger than 6 months of age enrolled in a prospective study
      of genetic polymorphisms and neurodevelopmental outcomes who were undergoing
      repair of two-ventricle cardiac defects. Neurodevelopmental outcomes at 1 year of
      age were assessed with the Bayley Scales of Infant Development-II, yielding two
      indices: Mental Developmental Index and Psychomotor Developmental Index. RESULTS:
      Surgical repair was performed in 247 infants with 1 in-hospital and 3 late
      deaths. Neurodevelopmental evaluation was performed in 188 of 243 (77%)
      survivors. Glucose levels at cardiac intensive care unit admission and during the
      first 48 postoperative hours were available for 180 of 188 patients. Mean
      admission glucose was 328 +/- 106 mg/dL; maximum glucose was 340 +/- 109 mg/dL.
      At least one glucose was greater than 200 mg/dL in 160 of 180 patients, and 49 of
      180 patients (27%) had a glucose greater than 400 mg/dL. Only 1 patient had a
      glucose less than 50 mg/dL. Female sex (p = 0.02), but no other patient or
      operative variable, was associated with higher glucose levels. Mean Mental
      Developmental Index and Psychomotor Developmental Index were 90.6 +/- 14.9 and
      81.6 +/- 17.2, respectively. Hyperglycemia was not associated with lower Mental
      Developmental Index and Psychomotor Developmental Index scores for the entire
      cohort or for neonates alone. CONCLUSIONS: Hyperglycemia is common early after
      infant cardiac surgery, but is not associated with worse neurodevelopmental
      outcome at 1 year of age.

PMID- 18036935
TI  - Mitral valve repair for infective endocarditis in children.
AB  - BACKGROUND: Surgery for mitral valve endocarditis in children is relatively
      uncommon. This study assesses its operative outcome and reoperation and long-term
      survival rates. METHODS: We reviewed the cases of 8 consecutive children who
      underwent mitral valve repair for infective endocarditis between 1989 and 2005 at
      our institution. Mean age was 13.8 years (range, 9.4 to 16.9 years). The mitral
      valve was affected in all 8 patients, and both aortic and mitral valve in 2.
      Congenital cardiac malformation was the predisposing factor in 3 patients. Three
      patients had floppy mitral valve owing to leaflet perforation. All 8 patients had
      severe mitral regurgitation. Indications for operations were cardiac failure in
      2, septic embolization in 2, and severe mitral regurgitation in 4. Four surgical
      interventions were elective, two were urgent, and two were emergencies. The
      offending microorganism was identified in 7 of the 8 patients. Mitral valve
      repair or reconstruction was performed in all 8, and 2 patients had additional
      aortic valve replacement. Follow-up was complete (mean, 9.5 years; range, 0.67 to
      16 years; total, 76.7 patient-years). RESULTS: There were no operative deaths.
      Actuarial freedom from reoperation and actuarial survival rate at 1, 5, 10, and
      15 years were 100%. Early echocardiographic follow-up showed 4 patients to have
      mild mitral valve regurgitation, 2 had mild to moderate, and 2 had no
      regurgitation. Long-term follow-up showed no progression of the lesions.
      CONCLUSIONS: Mitral valve repair achieves excellent results and can be performed
      without morbidity or mortality. Functional improvement and follow-up
      echocardiography evaluating the degree of mitral valve regurgitation and stenosis
      are satisfactory.

PMID- 18036936
TI  - Invited commentary. Infective endocarditis (IE) in children occurs overwhelmingly
      in individuals who have surgically treated and untreated structural heart
      disease.

PMID- 18036937
TI  - Brain natriuretic peptide levels before and after ventricular septal defect
      repair.
AB  - BACKGROUND: Brain natriuretic peptide is a relatively recently discovered
      circulating mediator that has been correlated with the degree of heart failure in
      adults. This study evaluated the preoperative and postoperative brain natriuretic
      peptide levels in infants and children undergoing ventricular septal defect
      repair. METHODS: The study enrolled 18 infants and children (ages 2 months to
      15.6 years) scheduled for surgical repair of their ventricular septal defects.
      Brain natriuretic peptide levels were drawn preoperatively and then
      postoperatively at 1, 24, 48, and 72 hours. The amount of shunt (the ratio of
      pulmonary blood flow [Q(p)]/systemic blood flow [Q(s)]) through the ventricular
      septal defect was determined by saturation levels performed in the
      catheterization laboratory or intraoperatively. RESULTS: The preoperative brain
      natriuretic peptide levels (pg/mL) averaged 78 +/- 57, and the postoperative
      levels were 168 +/- 241 at 1 hour, 418 +/- 330 at 24 hours, 405 +/- 364 at 48
      hours, and 391 +/- 397 at 72 hours. These differences were significant for each
      postoperative time point compared with preoperative values. Preoperative brain
      natriuretic peptide and the Q(p)/Q(s) were significantly correlated (age-adjusted
      R(2) = 0.33, p < 0.001). CONCLUSIONS: Brain natriuretic peptide levels have a
      close correlation with the physiologic volume load caused by ventricular septal
      defects. The preoperative brain natriuretic peptide levels were also found to be
      predictive for the postoperative time course of brain natriuretic peptide level
      changes. These results suggest that brain natriuretic peptide levels may be a
      useful clinical marker in infants and children with ventricular septal defects.

PMID- 18036938
TI  - Two thousand Blalock-Taussig shunts: a six-decade experience.
AB  - BACKGROUND: The Blalock-Taussig shunt (BTS) remains valuable for palliation of
      congenital heart disease, but its role has evolved. We reviewed our total
      institutional experience with BTS to examine changes in its use and outcomes.
      METHODS: A retrospective review was performed of all patients undergoing BTS at
      our institution from November 1944 to May 2006. Hospital records and autopsy
      records were evaluated to determine patient demographics, diagnoses, operative
      data, hospital complications, and long-term outcomes. RESULTS: During the last 62
      years, 2,016 BTS were performed by 28 surgeons on 1,880 patients from 35
      countries. Classic BTS were performed in 75% (1,503 of 2,016 BTS). Diagnosis was
      tetralogy of Fallot in 72% (1,294 of 1,802), although diagnoses were imprecise in
      the early part of the series. Overall operative mortality was 14% (227 of 1,574).
      On follow-up, 32% of tetralogy of Fallot patients (411 of 1,294 patients)
      underwent subsequent total correction at our institution, and an additional 116
      patients for whom follow-up was available had total correction of tetralogy of
      Fallot at other institutions, a combined total correction of tetralogy of Fallot
      rate of 41%. Of patients with complex congenital heart defects, 26% (106 of 404
      patients) had subsequent cavopulmonary connection or atrial or arterial switch
      procedures. A comparison of the first and second halves of the series revealed
      several trends: decreasing mean annual number of BTS (66/year versus 9/year,
      respectively), decreasing operative mortality (16% versus 9%), and increasing
      proportion of single-ventricle diagnoses (5% versus 34%). CONCLUSIONS: Evolution
      of the BTS has seen a decrease in overall use, particularly in tetralogy of
      Fallot, but greater application to single-ventricle cardiac lesions and improved
      operative survival.

PMID- 18036939
TI  - The use of the LigaSure Vessel Sealing System in esophageal cancer surgery.
AB  - PURPOSE: In this clinical study we investigated the use and results of the
      LigaSure Vessel Sealing Sytem (LVSS) (Valleylab, Boulder, CO) compared with
      conventional surgery in esophageal cancer resection. DESCRIPTION: The LVSS
      (Valleylab) is a device with a hemostatic design frequently used in abdominal
      surgery. Sixty patients (n = 30 in each group) with esophageal cancer from a
      single center were evaluated to undergo esophagectomy using either the LVSS or
      conventional clamping methods. The main outcome measures (ie, operating time,
      intraoperative blood loss, and postoperative course) were then compared.
      EVALUATION: In resections performed using the LVSS, operation duration (307 +/-
      35 minutes vs 260 +/- 35 minutes; p = 0.000), intraoperative blood loss (average
      533 +/- 211 mL vs 390 +/- 256 mL; p = 0.022), and postoperative drainage volumes
      (abdomen, 70 +/- 86 mL vs 40 +/- 61 mL; p = 0.122; thorax, 690 +/- 646 mL vs 540
      +/- 359 mL; p = 0.271) all decreased. CONCLUSIONS: The LVSS is easy to use and a
      reliable method in esophageal cancer surgery. Compared with conventional
      hemostatic techniques a reduction in intraoperative and postoperative blood loss,
      and a shortening of operation duration were determined. We believe that the use
      of the LVSS in esophageal surgery will become even more widespread in the future.

PMID- 18036940
TI  - Invited commentary. The use of LigaSure system device in esophagectomy.

PMID- 18036941
TI  - A novel adjustable pulmonary artery banding system for hypoplastic left heart
      syndrome.
AB  - PURPOSE: We describe the first case in which a neonate with hypoplastic left
      heart syndrome was initially managed using a mini adjustable banding system.
      DESCRIPTION: Through a mid-sternotomy, a 5-day-old neonate underwent bilateral
      pulmonary artery banding using this new system, combined with placement of a main
      pulmonary artery to the innominate artery shunt. EVALUATION: The patient had an
      uneventful postoperative course. Three percutaneous adjustments of the banding
      system were necessary to keep the arterial oxygen saturation in the 75% to 85%
      range. On day 48 of life, she was submitted to stent placement (6 mm) within the
      atrial septum to treat a restrictive atrial septal defect. Afterward, seven
      additional percutaneous adjustments of the banding system were necessary. The
      Norwood operation and the bidirectional Glenn shunt were carried out on the day
      106 of life. The bands were removed with no pulmonary artery distortion.
      CONCLUSIONS: The clinical use of this innovative pulmonary artery banding system
      was feasible, safe, and effective. This allowed for customization of the
      pulmonary blood flow according to the underlying clinical needs, resulting in a
      more precise balance between the pulmonary and systemic circulations.

PMID- 18036942
TI  - Massive hemoptysis in an immunocompromised pregnant woman with human
      immunodeficiency virus disease and active pulmonary tuberculosis.
AB  - Massive hemoptysis during pregnancy has been infrequently reported. The
      management of massive hemoptysis in an immunocompromised 22-year-old woman
      positive for human immunodeficiency virus undergoing treatment for cavitating
      pulmonary tuberculosis in the last trimester of pregnancy is reported. The
      difficulties encountered in applying our standard protocol for massive hemoptysis
      in this instance are described. The patient was managed by emergency cesarean
      section and lobectomy.

PMID- 18036943
TI  - Unilateral pulmonary edema after pulmonary embolism in a bilateral lung
      transplant patient.
AB  - We report a case of unilateral pulmonary edema due to the decompensation of an
      asymptomatic ipsilateral pulmonary venous stenosis by a contralateral pulmonary
      embolism. Emergency surgery included pulmonary embolectomy and refashioning of
      the stenotic pulmonary venous anastomosis.

PMID- 18036944
TI  - Management of an anterior mediastinal pheochromocytoma causing tracheomalacia.
AB  - Thoracic paragangliomas are rare tumors that arise from extra-adrenal chromaffin
      cells and have the capacity to secrete catecholamines. Surgical excision is the
      optimal treatment of these tumors as they are resistant to chemotherapy and
      radiation therapy. Although these tumors are most commonly found in the abdomen,
      10% of paraganagliomas are located in the thorax, usually in the posterior
      mediastinum. Occasionally these tumors present in the anterior mediastinum, which
      can pose a significant surgical challenge due to the proximity of the great
      vessels and airway. In this report we describe the treatment of an anterior
      mediastinal pheochromocytoma that presented with tracheal obstruction and
      required pulmonary artery reconstruction and airway stenting.

PMID- 18036945
TI  - Radiofrequency thermoablation in chest wall mesenchymal hamartoma of an infant.
AB  - We report on an infant presenting with a chondroid hamartoma managed with a
      combined conservative surgical treatment and radiofrequency thermoablation.

PMID- 18036946
TI  - Endoscopic management for broncholithiasis with bronchoesophageal fistula.
AB  - We report a case of broncholithiasis with bronchoesophageal fistula that was
      successfully managed endoscopically using endoscopic laser therapy and a covered
      self-expandable metallic stent.

PMID- 18036947
TI  - Good syndrome coexisting with leukopenia.
AB  - A 61-year-old man was admitted to our hospital for further examinations of a
      mediastinal mass. He had underwent an extended thymothymectomy, and had a tumor
      that was diagnosed as a type B1 thymoma, according to the World Health
      Organization. One year after surgery he was admitted again for recurrent diarrhea
      and pneumonia. Laboratory data revealed severe hypogammaglobulinemia with
      leukopenia. He was diagnosed with Good syndrome with leukopenia. Regular gamma
      globulin and figrastim injections were successful in keeping the patient symptom
      free. The prognosis of patients with Good syndrome and leukopenia is very poor;
      therefore, immediate diagnosis is important. The development of infectious
      diseases in a patient with thymoma or after the resection of thymoma mandates
      early and comprehensive immunologic investigation.

PMID- 18036948
TI  - Delayed repair of acute type A aortic dissection in a patient with
      gastrointestinal bleeding and pulse deficit.
AB  - Acute type A aortic dissections are considered surgical emergencies because these
      patients are at risk for life-threatening complications. Patients who present
      with significant neurologic and other end-organ malperfusion may benefit from a
      more conservative approach. We present a patient with type A aortic dissection
      and concomitant mesenteric and limb ischemia.

PMID- 18036949
TI  - Ileofemoral malperfusion complicating type a dissection: revascularization
      prevents renal failure.
AB  - We report four cases of lower extremity malperfusion complicating acute type A
      dissection. Two patients were treated with acute type A dissection repair,
      followed by axillobifemoral bypass grafting when malperfusion persisted after
      aortic replacement and required dialysis. Two patients were managed with lower
      extremity revascularization procedures before acute type A dissection repair and
      had preserved renal function. Lower extremity revascularization before
      cardiopulmonary bypass minimizes ischemia and allows for controlled limb
      reperfusion under hypothermic conditions compared with delayed normothermic
      reperfusion when performed after acute type A dissection repair. This strategy
      may increase limb function salvage and decrease the incidence of dialysis after
      acute type A dissection repair in patients presenting with lower extremity
      malperfusion.

PMID- 18036950
TI  - Another pitfall in minimally invasive mitral valve repair.
AB  - We report a case of severe systolic anterior motion (SAM) and dynamic left
      ventricular outflow obstruction after repair of a flail posterior leaflet of the
      mitral valve. The reason for SAM was found to be due to traction on the
      pericardial stay sutures placed to expose the surgical field. The SAM and the
      outflow obstruction were completely resolved by cutting these sutures. Our case
      demonstrates the contribution of geometric factors in the development of SAM and
      left ventricular outflow obstruction and emphasizes the need to evaluate the
      heart in its natural position within the mediastinum.

PMID- 18036951
TI  - Pulmonary thromboembolism with floating thrombus trapped in patent foramen ovale.
AB  - A 39-year-old man was hospitalized with symptoms of acute deep vein thrombosis,
      and computed tomography showed that he had pulmonary thromboembolism.
      Transthoracic echocardiography showed a large, right atrial thrombus and
      transesophageal echocardiography showed migrating thrombus trapped in a patent
      foramen ovale and extending all the way up to the ascending aorta. He underwent
      surgical embolectomy under cardiopulmonary bypass. At the conclusion of the
      operation, repeat transesophageal echocardiography examination revealed fresh but
      small thrombus in the right atrium. This continued entry of thrombi into the
      heart was further managed with fluoroscopy-guided insertion of a retrievable
      inferior vena cava filter through the internal jugular vein in the operating room
      itself.

PMID- 18036953
TI  - Severe chronic pulmonary hypertension caused by pulmonary embolism of hydatid
      cysts.
AB  - Severe pulmonary hypertension caused by chronic pulmonary thromboembolism may
      still present an indication for lung transplantation. We report a rare case in
      which severe pulmonary hypertension developed after pulmonary embolism of hydatid
      cysts. Successful treatment in this patient was achieved by complete pulmonary
      endarterectomy of the hydatid cysts.

PMID- 18036952
TI  - Epicardial left ventricular mapping using subxiphoid video pericardioscopy.
AB  - We report a novel subxiphoid video pericardioscopy approach for epicardial
      mapping that allows direct visualization of the epicardium with minimal use of
      fluoroscopy. The FLEXview system (Boston Scientific Cardiac Surgery, Santa Clara,
      CA), which is capable of a free navigation around the heart owing to its flexible
      neck, was inserted into the pericardial space through a small subxiphoid
      incision. A commercially available mapping catheter advanced through the working
      port of the device could be navigated around virtually the entire biventricular
      epicardial surface. The subxiphoid video pericardioscopy approach using the
      FLEXview system provided adequate visualization and access to the epicardium of
      both ventricles for electroanatomic mapping while minimizing surgical
      invasiveness.

PMID- 18036954
TI  - Resolution of protein-losing enteropathy with low-molecular weight heparin in an
      adult patient with Fontan palliation.
AB  - Protein-losing enteropathy is a well-known complication after the Fontan
      procedure, and unfractionated heparin therapy has been tried with some success as
      a potential therapy. Low-molecular weight heparin is believed to be ineffective.
      We now describe a case in which an adult patient with protein-losing enteropathy
      after Fontan palliation was successfully treated with systemic doses of low
      molecular weight heparin, with complete resolution in the 24-hour fecal alpha-1
      anti-trypsin level and serum albumin. The patient continues to remain in
      remission with this therapy. In conclusion, these findings are novel and compel
      us to re-evaluate our pathophysiologic understanding of this difficult condition.

PMID- 18036955
TI  - Staged hybrid left pulmonary artery rehabilitation in post-fontan left pulmonary
      artery hypoplasia.
AB  - Left pulmonary artery hypoplasia in the setting of Fontan circulation predisposes
      to pulmonary artery discontinuity. We describe a novel approach to correct post
      Fontan left pulmonary artery discontinuity by a strategy to produce isolated left
      pulmonary artery growth, followed by a catheter-based reincorporation of the left
      pulmonary artery into the Fontan circuit.

PMID- 18036956
TI  - A child with sickle cell disease and anomalous right coronary artery.
AB  - Sickle cell disease in children requiring open heart surgical repair is uncommon
      and requires specific perioperative interventions to avoid complications from
      intravascular red cell sickling. We present a rare case of a 14-year-old girl
      with sickle cell disease and an anomalous right coronary artery from the
      pulmonary artery.

PMID- 18036957
TI  - Demonstration of an intrathoracic rib with computed tomography and three
      dimensional reconstruction.

PMID- 18036958
TI  - Giant inflammatory ascending aorta aneurysm.

PMID- 18036959
TI  - Sinus of valsalva aneurysm masquerading as coronary artery disease.

PMID- 18036960
TI  - Laparoscopic and thoracoscopic Ivor Lewis esophagectomy with colonic
      interposition.
AB  - Minimally invasive esophagectomy is a feasible and safe alternative to open
      esophagectomy. The stomach is the preferred conduit for gastrointestinal
      reconstruction after esophagogastrectomy; however, if the stomach is not usable,
      the colon can be interposed as an alternative conduit. We describe the technique
      of minimally invasive Ivor Lewis esophagogastrectomy in a patient with a gastric
      cardia cancer involving the gastric body and distal esophagus. Laparoscopic
      colonic interposition using the right colon based on the middle colic vessels was
      used to restore gastrointestinal continuity.

PMID- 18036961
TI  - A simple method for making photographic records under sterile conditions.
AB  - Digital photography has become a practical alternative to conventional film
      photography for medical documentation, communication, and education. The use of
      digital cameras has become increasingly popular in recent years for documenting
      perioperative conditions, intraoperative findings, and imaging studies. However,
      taking intraoperative pictures or video clips may be technically demanding for
      assistants or nurses. Herein, we describe a simple and effective method for
      surgeons to create photographic and video records of operations under sterile
      conditions involving the use of a digital camera encased in commercially
      available protective housing.

PMID- 18036962
TI  - Pre-measured artificial chordae for mitral valve repair.
AB  - There is growing interest in the application of artificial chordae to correct
      mitral valve regurgitation caused by prolapse. Application of pre-measured
      artificial chordae facilitates creation of chordae of appropriate length. Herein
      we illustrate the technique for creation of pre-measured artificial chordae,
      documenting neo-chordal length and number in 50 patients with anterior leaflet
      prolapse, highlighting the need for chordae of more than one length in 14% of
      patients.

PMID- 18036963
TI  - Papillary muscle approximation for functional ischemic mitral regurgitation.
AB  - In patients with ischemic left ventricular dysfunction and functional mitral
      regurgitation, surgical treatment of mitral insufficiency remains a challenging
      issue. Several procedures have been described to restore a near to natural
      alignment between the mitral annulus and the laterally displaced papillary
      muscles. We report a new approach to relocate the displaced papillary muscles
      toward the mitral annulus and to reduce tethering in 8 patients, providing
      satisfactory initial results. Echocardiography showed mild or no mitral
      regurgitation at the follow-up (mean, 11.4 +/- 3.6 months; range = 7 to 14
      months). This procedure is believed to be technically easy and beneficial in
      terms of mitral repair.

PMID- 18036964
TI  - An alternative procedure for correction of anomalous origin of left 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 is commonly associated with mitral
      insufficiency. Direct implantation of the anomalous origin of the left coronary
      artery from the pulmonary artery into the aorta is ideal, but it may not be fit
      for some patients whose anomalous left coronary arteries arise remotely from the
      ascending aorta. To solve the same technical problem in a boy with anomalous
      origin of the left coronary artery from the pulmonary artery in combination with
      moderate mitral insufficiency, we successfully elongated the anomalous coronary
      artery by creating a tube-shape graft using part of the pulmonary arterial wall.
      Simultaneous mitral annuloplasty was performed after a dual-coronary repair.

PMID- 18036965
TI  - The unifocal bilateral bidirectional cavopulmonary anastomosis.
AB  - We propose a new surgical technique to manage the presence of bilateral superior
      venae cavae in single ventricle patients, a recognized risk factor for both
      bidirectional Glenn anastomosis and Fontan completion. The idea is to convert two
      small, peripheral and competing bilateral bidirectional cavopulmonary anastomoses
      into a single, larger, and centrally located cavopulmonary connection. This
      technique, used in 2 patients, provides a symmetrical distribution of pulmonary
      blood flow and may, in fact, yield growth of the central pulmonary arteries as
      well as prevent thrombus formation.

PMID- 18036966
TI  - Video-assisted thoracoscopic lung biopsy in patients with interstitial lung
      disease.

PMID- 18036967
TI  - Pleurodesis using small talc particles results in an unacceptably high rate of
      acute lung injury and hypoxia.

PMID- 18036969
TI  - Decreasing the expression of LFA-1 and ICAM-1 as well as hindering their
      interaction as the major mechanism for statin-induced neutrophil dysfunction.

PMID- 18036970
TI  - GATA4 as candidate gene for pericardial defects.

PMID- 18036971
TI  - Internal thoracic artery grafts and upper extremity arteriovenous fistula.

PMID- 18036972
TI  - Management of tricuspid valve replacement.

PMID- 18036973
TI  - Rhythmic movement disorder.

PMID- 18036974
TI  - Sleepiness and brief lapses of consciousness.

PMID- 18036975
TI  - The NIDRR burn injury rehabilitation model system program: selected findings.
AB  - The NIDRR burn injury rehabilitation model system program: selected findings. The
      quality of burn care has improved over the past few decades, and consequently
      many more survivors with large-area burn injuries have long-term rehabilitation
      needs. The National Institute on Disability Rehabilitation Research recognized
      that the rehabilitation of people with burn injuries has been underaddressed and
      established model systems of care for this population in 1994. This special
      supplement to the Archives of Physical Medicine and Rehabilitation reports on
      some of the research that has been generated by the Burn Rehabilitation Model
      Systems over the past 13 years.

PMID- 18036976
TI  - Augmented exercise in the treatment of deconditioning from major burn injury.
AB  - OBJECTIVE: To investigate the efficacy of a 12-week exercise program in producing
      greater improvement in aerobic capacity in adult burn survivors, relative to
      usual care. DESIGN: Randomized, controlled, double-blinded trial. SETTING: Burn
      center. PARTICIPANTS: A population-based sample of 35 adult patients admitted to
      a burn center for treatment of a serious burn injury. INTERVENTION: A 12-week, 36
      session, aerobic treadmill exercise program where work to quota (WTQ)
      participants intensified their exercise according to preset quotas and work to
      tolerance (WTT) participants continued to their tolerance. Participants completed
      a maximal stress test at baseline and 12 weeks to measure physical fitness. MAIN
      OUTCOME MEASURE: Maximal aerobic capacity. RESULTS: The WTT and the WTQ exercise
      groups both made significant improvements in aerobic capacity from baseline to 12
      weeks (t=-3.60, P< or =.01; t=-3.17, P< or =.01, respectively). The control group
      did not (t=-1.39, P=.19). WTT and WTQ participants demonstrated significantly
      greater improvements in aerobic capacity in comparison to the control group
      members (F=4.6, P< or =.05). The WTT and WTQ groups did not differ significantly
      from each other with regard to their respective improvements in aerobic capacity
      (F=.014, P=.907). CONCLUSIONS: The aerobic capacity of adult burn survivors can
      be improved with participation in a structured, 12-week exercise program after
      injury.

PMID- 18036977
TI  - Effects of cessation of a structured and supervised exercise conditioning program
      on lean mass and muscle strength in severely burned children.
AB  - OBJECTIVE: To determine whether the benefits of exercise by burned children are
      maintained 3 months after the exercise program is concluded. DESIGN: Randomized,
      controlled prospective study. SETTING: Pediatric burn hospital. PARTICIPANTS:
      Twenty severely burned children with a 40% or greater total body surface area
      burn, with main outcome measures completed before exercise training, immediately
      after 12 weeks of exercise training (intervention), and 12 weeks after training
      ended. INTERVENTION: Randomization into a 12-week standard rehabilitation program
      at home (n=9) or a 12-week standard hospital rehabilitation program supplemented
      with an exercise-training program beginning 6 months after burn injury (n=11).
      MAIN OUTCOME MEASURES: Assessment of lean body mass (LBM) using dual-energy x-ray
      absorptiometry and of leg isokinetic muscle strength at a speed of 150 degrees /s
      were done before, after the 12-week rehabilitation and exercise training program,
      and 3 months after the exercise program was completed (12mo postburn). The
      effects of exercise on the dependent variables were analyzed by repeated-measures
      analysis of variance. If we found a significant overall effect of time and/or
      intervention, we did a post hoc test for multiple comparison (Holm-Sidak).
      Results are expressed as mean +/- standard error. RESULTS: The mean percentage
      increase in LBM and muscle strength was significantly greater in the exercise
      group (6.4%+/-1.9%, 40.7%+/-8.6%, respectively) than in the no-exercise group
      (1.9%+/-2.6% vs 3.4%+/-4.5%, respectively). Three months after cessation of the
      exercise program, LBM remained relatively unchanged in the no-exercise group
      (3.5%+/-1.8%). In contrast, LBM in the exercise group increased significantly
      (10.7%+/-4.8%, P=.03). In addition, muscle strength further increased by 17.9%+/
      10.1% in the exercise group versus 7.2%+/-3.4% in the no-exercise group, although
      neither percentage increase was significant (P=.08 for exercise vs P=.61 for no
      exercise). Absolute values in LBM and muscle strength for both groups at 12
      months postburn continued to be below historical or concurrent age-matched,
      nonburned children. CONCLUSIONS: Participation in an exercise program resulted in
      a greater improvement in LBM and muscle strength in the exercise group than in
      the no-exercise group. Three months after the exercise training ended, there were
      persistent mild-to-moderate increases in LBM and muscle strength. Absolute levels
      continued to be below previously reported nonburned, age-matched values, however,
      which underscores the need for continued exercise to improve LBM and muscle
      strength in severely burned children.

PMID- 18036978
TI  - Burn rehabilitation: an overview.
AB  - Burn injuries result in significant physical and psychologic complications that
      require comprehensive rehabilitation treatment and coordination with the acute
      care burn team. This interdisciplinary rehabilitation treatment is focused on
      preventing long-term problems with scarring, contractures, and other problems
      that limit physical function. Adequate pain management and recognition of
      psychologic issues are important components of treatment after burn injuries.
      Burn injuries present significant barriers to community integration, but many
      people can successfully return to work and other activities.

PMID- 18036979
TI  - Outcomes after deep full-thickness hand burns.
AB  - OBJECTIVE: To measure hand-specific functional performance after deep full
      thickness dorsal hand burns. DESIGN: Descriptive, cross-sectional study. SETTING:
      The 2005 Phoenix Society's World Burn Congress, Baltimore, MD. PARTICIPANTS:
      Volunteer sample of burn survivors (N=32) with full-thickness dorsal hand burns
      with extensor mechanism involvement, who consented to participate. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Total active motion of joints, Jebsen
      Taylor Hand Function Test (JTHFT), and Michigan Hand Questionnaire (MHQ).
      RESULTS: Subjects had large burns (mean percentage total body surface area, 58%).
      Digit involvement was severe, with more than 50% having amputations and 22% with
      a boutonniere deformity. Forty percent of subjects had poor functional range with
      total active motion of less than 180 degrees . Scores on the JTHFT were lower
      than normative scores, and subjects reported most difficulty in performing MHQ
      activities of daily living (ADLs). CONCLUSIONS: Even with partial amputation or
      loss of extensor mechanisms, the intact flexor muscles facilitate function by
      allowing for a modified grasp and enable patients to be independent in most ADL
      tasks. Training programs can be developed to meet specific goals despite residual
      hand deformities caused by deep full-thickness burns.

PMID- 18036980
TI  - Acute pain at discharge from hospitalization is a prospective predictor of long
      term suicidal ideation after burn injury.
AB  - OBJECTIVE: To determine the extent to which pain contributes to risk for suicidal
      ideation after burn injury. DESIGN: This longitudinal cohort study evaluated
      participants at discharge, 6 months, and 1 year after burn injury. SETTING:
      Inpatient rehabilitation units of multiple regional burn centers. PARTICIPANTS:
      Survivors of major burns (N=128). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Pain severity, assessed using the Medical Outcomes Study 36-Item Short
      Form Health Survey bodily pain subscale, and passive and active suicidal
      ideation, assessed by self-report. RESULTS: At each time point, approximately one
      quarter to one third of the sample reported some form of suicidal ideation. In
      logistic regression analyses, pain severity at discharge was the sole consistent
      predictor of suicidal ideation at follow-up, with greater pain severity being
      associated with enhanced risk for both passive and active suicidal ideation.
      These associations were observed even after controlling for discharge mental
      health. CONCLUSIONS: These are the first findings to suggest an association
      between acute pain severity and the development and maintenance of suicidal
      ideation in burn patients. Further research in this area, including the study of
      improved pain management programs as a prophylaxis against suicidal ideation, may
      benefit those who are at elevated suicide risk as a consequence of burn injuries.

PMID- 18036981
TI  - Factors influencing the efficacy of virtual reality distraction analgesia during
      postburn physical therapy: preliminary results from 3 ongoing studies.
AB  - OBJECTIVE: To assess the efficacy and side effects of immersive virtual reality
      (VR) distraction analgesia, as well as patient factors associated with VR
      analgesic efficacy in burn patients who require passive range-of-motion (ROM)
      physical therapy (PT). DESIGN: Prospective, randomized, controlled, within
      subject trials. SETTING: Regional level I burn center in a university-affiliated
      urban hospital. PARTICIPANTS: Patients (age range, 6-65y) who required passive
      ROM PT in sessions lasting 3 to 15 minutes after cutaneous burn injury.
      INTERVENTIONS: Standard analgesic (opioid and/or benzodiazepine) care and
      standard analgesic care plus immersive VR distraction. MAIN OUTCOME MEASURE: Self
      reported subjective pain ratings (0 to 100 graphic rating scale). RESULTS: A
      total of 146 treatment comparisons were made in 88 subjects, 75% of whom were
      children ages 6 to 18 years. Compared with standard analgesic treatment alone,
      the addition of VR distraction resulted in significant reductions in subjective
      pain ratings for worst pain intensity (20% reduction), pain unpleasantness (26%
      reduction), and time spent thinking about pain (37% reduction). Subjects' age,
      sex, ethnicity, size of initial burn injury, or duration of therapy session did
      not affect the analgesic effects of VR distraction. Nausea with the standard care
      plus VR distraction condition was infrequent (15%) and mild, with 85% of the
      subjects reporting no nausea. Children provided higher subjective reports of
      "presence" in the virtual environment and "realness" of the virtual environment
      than did adults, but age did not affect the analgesic effects of VR distraction.
      CONCLUSIONS: When added to standard analgesic therapy, VR distraction provides a
      clinically meaningful degree of pain relief to burn patients undergoing passive
      ROM PT. Multiple patient factors do not appear to affect the analgesic effect.
      Immersive VR distraction is a safe and effective nonpharmacologic technique with
      which to provide adjunctive analgesia to facilitate patient participation in
      rehabilitation activities.

PMID- 18036982
TI  - Barriers to return to work after burn injuries.
AB  - OBJECTIVE: To identify barriers to return to work after burn injury as identified
      by the patient. DESIGN: A cohort study with telephone interview up to 1 year.
      SETTING: Hospital-based burn centers at 3 national sites. PARTICIPANTS:
      Hospitalized patients (N=154) meeting the American Burn Association criteria for
      major burn injury, employed at least 20 hours a week at the time of injury, and
      with access to a telephone after discharge. INTERVENTION: Patients were contacted
      via telephone every 2 weeks up to 4 months, then monthly up to 1 year after
      discharge. MAIN OUTCOME MEASURES: A return to work survey was used to identify
      barriers that prevented patients from returning to work. A graphic rating scale
      determined the impact of each barrier. RESULTS: By 1 year, 79.7% of patients
      returned to work. Physical and wound issues were barriers early after discharge.
      Although physical abilities continued to be a significant barrier up to 1 year,
      working conditions (temperature, humidity, safety) and psychosocial factors
      (nightmares, flashbacks, appearance concerns) became important issues in those
      with long-term disability. CONCLUSIONS: The majority of patients return to work
      after a burn injury. Although physical and work conditions are important
      barriers, psychosocial issues need to be evaluated and treated to optimize return
      to work.

PMID- 18036983
TI  - Physical and psychologic rehabilitation outcomes for young adults burned as
      children.
AB  - OBJECTIVE: To report physical and psychologic outcomes for young adult survivors
      of pediatric burns. DESIGN: Prospective, correlational study. SETTING: Acute and
      rehabilitation pediatric burn care facility. PARTICIPANTS: Eighty-three young
      adult survivors of pediatric burns, who were 18 to 28 years of age, with total
      body surface area (TBSA) burns of 30% or greater, and were at least 2 years
      postburn. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Physical outcomes
      were assessed by muscle strength tests, grip and pinch measurements, mobility
      levels, and self-care (activities of daily living) skills. Psychologic outcomes
      included behavioral problems, personality disorder, and incidence of psychiatric
      illness. An individually administered Structured Clinical Interview for
      Diagnosis, based on the Diagnostic and Statistical Manual of Mental Disorders,
      4th Edition, for psychiatric diagnosis, was used to assess mental health, and
      behavioral problems were assessed with the Young Adult Self-Report. Participants
      reported educational achievement, employment status, state of transition from
      family of origin (home) to independent living, and pair bonding. The Short-Form
      36-Item Health Survey and the Quality of Life Questionnaire were used to assess
      each participant's self-reported general health and quality of life. RESULTS: The
      majority of subjects had physical and psychologic outcomes that were within the
      normal range when compared with age-mates who had not experienced burns. The
      areas that were most likely to be impaired involved peripheral strength (wrist
      and grip). These deficits affected some self-care skills and correlated with
      TBSA. Standardized diagnostic interviews showed that greater than 50% of subjects
      qualified for a psychiatric diagnosis, with anxiety disorders as the most
      frequently occurring diagnosis. There were few significant correlations of the
      physical measurements or self-care skills with the burn size, psychologic
      problems, or social outcomes, and none appeared to be clinically important.
      CONCLUSIONS: Most of the people in this sample were functioning physically and
      psychosocially within normal limits as they reached adulthood. Although they
      appeared to function well as measured by standardized assessments, there were
      indications of private suffering that suggested they may not be functioning at an
      optimal level. The findings suggest that rehabilitation professionals could
      improve outcomes by including programs to develop overall muscle strength in
      severely burned children and by addressing concerns related to anxiety and other
      symptoms of psychologic distress.

PMID- 18036984
TI  - Assets and liabilities of the Burn Model System data model: a comparison with the
      National Burn Registry.
AB  - OBJECTIVES: To determine whether the Burn Model System (BMS) population is
      representative of the larger burn population and to investigate threats to
      internal and external validity in a multicenter longitudinal database of severe
      burns. DESIGN: Cohort data for the BMS project have been collected since 1994.
      Follow-up data have been collected at 6, 12, and 24 months postburn. The
      demographic and burn characteristics of the BMS population were compared with
      those of patients in the National Burn Registry (NBR). SETTING: The BMS, which
      collected data for these analyses from 5 regional burn centers in the United
      States, and the NBR dataset, which is a registry of information collected through
      the Trauma Registry of the American College of Surgeons and includes data from 70
      hospitals in the United States and Canada. PARTICIPANTS: BMS study participants
      were severely burned patients treated at 1 of the 5 participating burn centers.
      We compared the BMS population with that of the NBR both in total and filtered to
      include only patients with comparable injuries. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Comparable demographic and burn characteristics contained
      in both the NBR and the 5-center BMS longitudinal database and baseline and
      follow-up distributions of demographic variables and burn characteristics in the
      BMS database. RESULTS: Although minor deviations in demographic distributions
      were found between the BMS and NBR and between discharge and follow-up
      populations, our results show that the BMS population sample is internally and
      externally valid and is adequate for answering research questions. CONCLUSIONS:
      Cohort studies examining long-term outcomes have the potential flaw of using a
      nonrepresentative study population. The BMS population was found to be
      sufficiently representative, but future analyses will require cautious and
      purposeful application of statistical adjustment strategies.

PMID- 18036985
TI  - Theoretically estimated risk of severe acute respiratory syndrome transmission
      through blood transfusion during an epidemic in Shenzhen, Guangdong, China in
      2003.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly recognized
      infectious disease that caused an outbreak in south China in 2003. The cause of
      SARS was identified as a novel coronavirus (CoV). The existence of asymptomatic
      seroconvertors and the detection of the SARS-CoV RNA in plasma during the course
      of infection all suggest that SARS could, as least theoretically, be transmitted
      by transfusion. An estimate of the risk of SARS transmission through blood
      transfusion will contribute to decisions concerning blood safety monitoring and
      may be useful in the design of strategies to decrease the risk of transfusion
      transmitted infections. STUDY DESIGN AND METHODS: Case onset dates from the 2003
      Shenzhen SARS epidemic and investigational results from Taiwan on viremia in
      humans are used to estimate the number of cases that were viremic throughout the
      epidemic. Estimates of the asymptomatic-to-clinically confirmed SARS-CoV
      infection ratio, the proportion of asymptomatic infections reported in a
      seroprevalence survey in Hongkong, and the population size of Shenzhen are used
      to infer the SARS-CoV transfusion-transmission risk. Statistical resampling
      methods are used. RESULTS: Based on data from Shenzhen, Hongkong and Taiwan, the
      maximum and mean risk (per million) of SARS-CoV transmission from donors in
      Shenzhen were estimated as 23.57 (95% CI: 6.83-47.69) and 14.11 (95% CI: 11.00
      17.22), respectively. The estimated risk peaked on April 02, 2003. CONCLUSIONS:
      Although there are currently no confirmed reports of the transmission of SARS-CoV
      from asymptomatic individuals, recent research data indicate that transfusion
      transmitted SARS-CoV is at least theoretically possible. Although the risk is
      low, with its rapid spread of the disease, appearance of alarmingly high
      infectivity and high fatality rate, public health authorities need to consider
      strategies for blood donor recruitment and virus inactivation during an epidemic
      to further ensure blood safety.

PMID- 18036986
TI  - In vitro evaluation of platelet concentrates during storage: Platelet counts and
      markers of platelet destruction.
AB  - BACKGROUND: Differences in platelet counts are observed by use of automated
      haematology analyzers making interlaboratory comparison difficult. MATERIALS AND
      METHODS: Twenty-eight single-donor platelet concentrates (PCs) were collected.
      Platelet concentration and markers of platelet destruction were investigated
      during storage for 11/12 days. RESULTS: Increasing impedance-immunoplatelet ratio
      was observed during storage, correlating to platelet fragments, large platelets,
      platelet density and cell-lysis. High variability was observed for optical
      immunoplatelet ratio. CONCLUSION: Immunoplatelet count or correction factor
      calculated by impedance-immunoplatelet ratio should be used to confirm that
      platelet unit meets platelet count requirements or to compare results from
      clinical trials. Optical platelet count is not recommended.

PMID- 18036987
TI  - The pathogenesis of transfusion-related acute lung injury and how to avoid this
      serious adverse reaction of transfusion.
AB  - Transfusion-related acute lung injury (TRALI) is a serious, life-threatening
      complication of blood transfusion. Available evidence strongly suggests that
      leukocyte antibodies present in donor plasma are the predominant mechanism in
      TRALI. These antibodies lead to recipient neutrophil activation, with activated
      neutrophils inducing endothelial and alveolar damage in the lungs. These
      mechanisms are discussed in detail as are the alternative mechanisms that have
      been proposed. Preventive strategies that may help to reduce TRALI are presented.

PMID- 18036988
TI  - History and evolution of Hemapheresis in Argentina.

PMID- 18036989
TI  - Immunoadsorption in dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is a common myocardial disease characterized by
      ventricular dilatation and progressive depression of myocardial contractile
      function. Disturbances in both humoral and cellular immunity have been described
      among these patients. A number of antibodies against various cardiac cell
      proteins have been identified in DCM. Recent data indicate that cardiac
      antibodies play an active role in the pathogenesis of DCM, and may contribute to
      cardiac dysfunction of DCM patients. Therefore, removal of cardiac autoantibodies
      by immunoadsorption may induce hemodynamic improvement in DCM patients. Various
      studies with a limited number of patients indicate that immunoadsorption improves
      left ventricular function in DCM.

PMID- 18036992
TI  - Optimizing healing of the acute wound by minimizing complications.

PMID- 18036993
TI  - SLE serum induces classical caspase-dependent apoptosis independent of death
      receptors.
AB  - The main source of autoantigens in systemic lupus erythematosus (SLE) is most
      likely apoptotic material. We have previously shown that sera from SLE patients
      can induce apoptosis in monocytes and lymphocytes, and here we characterized
      mechanisms of apoptosis induced by SLE serum. SLE serum seems to induce caspase
      dependent classical apoptosis since cells exposed to SLE serum displayed
      morphology consistent with classical apoptosis as demonstrated by confocal
      microscopy, and pan-caspase inhibitor Z-VAD.fmk significantly reduced SLE serum
      induced apoptosis. Death-receptor-independent pathways seemed to be involved
      since SLE serum induced apoptosis equally in FADD-mutant and wild-type Jurkat
      cell lines, and blocking of Fas and TNFR1 did not reduce apoptosis induction.
      Importantly, apoptosis was significantly reduced in a Bcl-2 overexpressing Jurkat
      cell line indicating involvement of mitochondrial pathways. Thus, based on
      morphology and caspase inhibition experiments, we have demonstrated that SLE
      serum induce classical caspase-dependent apoptosis, and this was independent of
      death receptor pathways.

PMID- 18036994
TI  - Profiles in comparative endocrinology: professor Arnold De Loof.

PMID- 18036995
TI  - Endometriosis: current and future medical therapies.
AB  - Endometriosis is a chronic inflammatory disease that responds to steroidal
      manipulation. Creation of a steady hormonal environment with inhibition of
      ovulation temporarily suppresses the ectopic implants and reduces the
      inflammatory status as well as the associated pain symptoms. Pharmacological
      management of endometriosis must be set within the framework of long-term
      therapeutic strategies. As the available drugs are not curative, treatments will
      need to be administered for years or until women desire a pregnancy. The various
      therapies studied have shown similar efficacy. Consequently, based on a more
      favourable profile in terms of safety, tolerability and cost, combined oral
      contraceptives and progestins should be considered as the first-line option, both
      as an alternative to surgery and as a postoperative adjuvant measure.
      Gonadotrophin-releasing hormone analogues, danazol and gestrinone should be used
      when progestins and oral contraceptives fail, are not tolerated or are contra
      indicated. Future therapies for endometriosis must compare favourably with
      existing drugs before hypothesizing their implementation in current practice.
      Medical treatment is not indicated in women seeking conception because
      reproductive prognosis is not ameliorated.

PMID- 18036996
TI  - Transcriptome analysis of differentiating spermatogonia stimulated with kit
      ligand.
AB  - Kit ligand (KL) is a survival factor and a mitogenic stimulus for differentiating
      spermatogonia. However, it is not known whether KL also plays a role in the
      differentiative events that lead to meiotic entry of these cells. We performed a
      wide genome analysis of difference in gene expression induced by treatment with
      KL of spermatogonia from 7-day-old mice, using gene chips spanning the whole
      mouse genome. The analysis revealed that the pattern of RNA expression induced by
      KL is compatible with the qualitative changes of the cell cycle that occur during
      the subsequent cell divisions in type A and B spermatogonia, i.e. the progressive
      lengthening of the S phase and the shortening of the G2/M transition. Moreover,
      KL up-regulates in differentiating spermatogonia the expression of early meiotic
      genes (for instance: Lhx8, Nek1, Rnf141, Xrcc3, Tpo1, Tbca, Xrcc2, Mesp1, Phf7,
      Rtel1), whereas it down-regulates typical spermatogonial markers (for instance:
      Pole, Ptgs2, Zfpm2, Egr2, Egr3, Gsk3b, Hnrpa1, Fst, Ptch2). Since KL modifies the
      expression of several genes known to be up-regulated or down-regulated in
      spermatogonia during the transition from the mitotic to the meiotic cell cycle,
      these results are consistent with a role of the KL/kit interaction in the
      induction of their meiotic differentiation.

PMID- 18036997
TI  - Brca1 in immunoglobulin gene conversion and somatic hypermutation.
AB  - Defects in Brca1 confer susceptibility to breast cancer and genomic instability
      indicative of aberrant repair of DNA breaks. Brca1 was previously implicated in
      the homologous recombination pathway via effects on the assembly of recombinase
      Rad51. Activation-induced cytidine deaminase (AID) deaminates C to U in B
      lymphocyte immunoglobulin (Ig) DNA to initiate programmed DNA breaks. Subsequent
      uracil-glycosylase mediated U removal, and perhaps further processing, leads to
      four known classes of mutation: Ig class switch recombination that results in a
      region-specific genomic deletion, Ig somatic hypermutation that introduces point
      mutations in Ig V-regions, Ig gene conversion in vertebrates that possess Ig
      pseudo-V genes, and translocations common to B cell lymphomas. We tested the
      involvement of Brca1 in AID-dependent Ig diversification in chicken DT40 cells.
      The DT40 cell line diversifies IgVlambda mainly by gene conversion, and less so
      by point mutation. Brca1-deficiency caused a shift in Vlambda diversification,
      significantly reducing the proportion of gene conversions relative to point
      mutations. Thus, Brca1 regulates AID-dependent DNA lesion repair. Interestingly,
      while Brca1 is required to recruit ubiquitinated FancD2 to DNA damage, the
      phenotype of Brca1-deficient DT40 differs from the one of FancD2-deficient DT40,
      in which both gene conversion and non-templated mutations are impaired.

PMID- 18036998
TI  - Bilateral sequential lung and simultaneous pancreas transplant: a new approach
      for the recipient with cystic fibrosis.
AB  - Cystic fibrosis (CF) is an inherited disorder that presents in childhood as a
      multisystem disease. Pulmonary failure and pancreatic insufficiency, including CF
      related diabetes (CFRD) and exocrine insufficiency, are common complications of
      this disease. In this report we review the first three simultaneous lung and
      pancreas transplantations in CF patients with diabetes. METHODS: All three CF
      patients presented for evaluation for lung transplantation and had pancreatic
      insufficiency requiring enzyme supplementation and CFRD requiring insulin. All
      were severely malnourished and required nutritional supplementation. SURGICAL
      TECHNIQUE: In each case, the allografts were procured from a single cadaveric
      donor. Bilateral lung transplantation was performed first using two separate
      thoracic incisions. The pancreas transplant was performed with systemic venous
      drainage and enteric exocrine drainage. RESULTS: The pancreas allografts all
      functioned normally with normoglycemia independent of insulin. As a result of the
      enteric drainage of the pancreas allograft, supplemental pancreatic enzymes were
      no longer required. Despite several complications detailed in the manuscript, all
      three remain independent of supplemental oxygen, insulin and pancreatic enzyme
      replacement at 4, 6 and 14 months of follow-up. CONCLUSION: Simultaneous lung and
      pancreas transplantation in patients with CF can be performed successfully and
      provides the advantages of normoglycemia and improves nutrition for patients
      requiring lung transplantation.

PMID- 18036999
TI  - Airway response to induced muscular contraction in spontaneously breathing
      rabbits.
AB  - The airways are thought to dilate during exercise in humans but the time course
      and mechanisms of the response are not fully described. The aim of the study was
      to document changes in airway calibre during electrically induced muscular
      contractions (MC) in spontaneously breathing rabbits. Experiments were also
      performed after induced bronchoconstriction to assess the effect of change in
      breathing pattern on airway calibre during MC. Respiratory resistance (R(RS)) was
      measured in 12 rabbits using the forced oscillation technique at 20 Hz before,
      during and after 30s MC in control conditions and after methacholine induced
      bronchoconstriction (Mch). MC was associated with significant decrease in R(RS)
      both at control and Mch. The MC induced increase in V(E) occurred with
      significant albeit small change in mean tidal volume (V(T)) at Mch but not
      control. An augmented breath (AB) occurred in 29/35 MCs and was usually
      associated with an abrupt drop in R(RS). The decrease in R(RS) induced by AB was
      significantly larger at Mch compared with control. Passively inflating the lung
      after MC induced significantly larger decrease in R(RS) than AB during MC. The
      data indicate bronchodilation by MC in spontaneously breathing rabbits. The
      mechanisms appear to include AB dependent airway wall stretching as well as
      removal of cholinergic input to the airway smooth muscle.

PMID- 18037000
TI  - The fall in exhaled nitric oxide with ventilation at low lung volumes in rabbits:
      an index of small airway injury.
AB  - The mechanisms involved in the fall of exhaled nitric oxide (NOe) concentration
      occurring in normal, anesthetized open chest rabbits with prolonged mechanical
      ventilation (MV) at low lung volume have been investigated. NOe, pH of exhaled
      vapor condensate, serum prostaglandin E(2), and F(2alpha), tumor necrosis factor
      (TNF-alpha), PaO(2), PaCO(2), pHa, and lung mechanics were assessed before,
      during, and after 3-4h of MV at zero end-expiratory pressure (ZEEP), with fixed
      tidal volume (9 ml kg(-1)) and frequency, as well as before and after 3-4h of MV
      on PEEP only. Lung histology and wet-to-dry ratio (W/D), and prostaglandin and
      TNF-alpha in bronchoalveolar lavage fluid (BALF) were also assessed. While MV on
      PEEP had no effect on the parameters above, MV on ZEEP caused a marked fall (45%)
      of NOe, with a persistent increase of airway resistance (45%) and lung elastance
      (12%). Changes in NOe were independent of prostaglandin and TNF-alpha levels,
      systemic hypoxia, hypercapnia and acidosis, bronchiolar and alveolar interstitial
      edema, and pH of exhaled vapor condensate. In contrast, there was a significant
      relationship between the decrease in NOe and bronchiolar epithelial injury score.
      This indicates that the fall in NOe, which occurs in the absence of an
      inflammatory response, is due to the epithelial damage caused by the abnormal
      stresses related to cyclic opening and closing of small airways with MV on ZEEP,
      and suggests its use as a sign of peripheral airway injury.

PMID- 18037003
TI  - Stress-induced changes in hippocampal function.
AB  - Exposure of an organism to stress leads to activation of the sympatho
      adrenomedullary system and the hypothalamo-pituitary-adrenal axis. Consequently,
      levels of noradrenaline, peptides like vasopressin and CRH, and corticosteroid
      hormones in the brain rise. These hormones affect brain function at those sites
      where receptors are enriched, like the hippocampus, lateral septum, amygdala
      nuclei, and prefrontal cortex. During the initial phase of the stress response,
      when hormone levels are high, these compounds mostly enhance excitability and
      promote long-term potentiation. Later on, when hormone levels have subsided but
      gene-mediated effects of corticosteroids start to appear, the excitability is
      normalized to the pre-stress level, in the CA1 hippocampal area, but possibly
      less so in the dentate gyrus and amygdala. A disturbed balance between these
      early and late phases of the stress response as well as a shift toward the
      relative contribution of the dentate/amygdala pathways may explain why the normal
      restorative capacity fails in vulnerable people experiencing a life-threatening
      situation, which could contribute to the development of PTSD.

PMID- 18037004
TI  - Glucocorticoids, developmental 'programming' and the risk of affective
      dysfunction.
AB  - Early life environmental events have persisting effects on tissue structure and
      function, a phenomenon called 'developmental programming'. Exposure to stress and
      its glucocorticoid hormone mediators may underpin many such effects. Indeed,
      studies in animal models and observations in humans suggest that prenatal
      stress/glucocorticoid overexposure causes permanent cardiometabolic,
      neuroendocrine and behavioural effects in offspring. Such effects appear mediated
      via tissue-specific changes in gene expression. Underlying epigenetic changes in
      target gene promoters may ensure persistence of altered transcription long after
      the initial challenge. Posttraumatic stress disorder and other affective diseases
      may both act as environmental challenges if present in early life and may
      themselves be more likely in individuals made 'vulnerable' by early life stress.

PMID- 18037005
TI  - Amygdala modulation of memory-related processes in the hippocampus: potential
      relevance to PTSD.
AB  - A key assumption in the study of stress-induced cognitive and neurobiological
      modifications is that alterations in hippocampal functioning after stress are due
      to an excessive activity exerted by the amygdala on the hippocampus. Research so
      far focused on stress-induced impairment of hippocampal plasticity and memory but
      an exposure to stress may simultaneously also result in strong emotional
      memories. In fact, under normal conditions emotionally charged events are better
      remembered compared with neutral ones. Results indicate that under these
      conditions there is an increase in activity within the amygdala that may lead to
      memory of a different quality. Studying the way emotionality activates the
      amygdala and the functional impact of this activation we found that the amygdala
      modulates memory-related processes in other brain areas, such as the hippocampus.
      However, this modulation is complex, involving both enhancing and suppressing
      effects, depending on the way the amygdala is activated and the hippocampal
      subregion examined. The current review summarizes our findings and attempts to
      put them in context with the impact of an exposure to a traumatic experience, in
      which there is a mixture of a strong memory of some aspects of the experience but
      impaired memory of other aspects of that experience. Toward that end, we have
      recently developed an animal model for the induction of predisposition to stress
      related disorders, focusing on the consequences of exposure to stressors during
      juvenility on the ability to cope with stress in adulthood. Exposing juvenile
      stressed rats to an additional stressful challenge in adulthood revealed their
      impairment to cope with stress and resulted in significant elevation of the
      amygdala. Interestingly, and similar to our electrophysiological findings,
      differential effects were observed between the impact of the emotional challenge
      on CA1 and dentate gyrus subregions of the hippocampus. Taken together, the
      results indicate that long-term alterations within the amygdala contribute to
      stress-related mnemonic symptoms and suggest that elucidating further these intra
      amygdala alterations and their effects on modulating other brain regions is
      likely to be beneficial for the development of novel approaches to treat stress
      related disorders.

PMID- 18037006
TI  - Commentary: neuroendocrine basis.

PMID- 18037007
TI  - Mice that under- or overexpress glucocorticoid receptors as models for depression
      or posttraumatic stress disorder.
AB  - Modern molecular and pathophysiological concepts suggest that glucocorticoid
      receptors (GRs) play a crucial role for the pathogenesis, course and therapy of
      affective or emotional disorders. Specifically, an impairment of GR signaling has
      been associated with major depression, whereas overactivity or
      hyperresponsiveness of GRs have been conceptualized for posttraumatic stress
      disorder (PTSD). Recently, several research groups have generated transgenic
      mouse strains that under- or overexpress GRs, respectively. These animals seem to
      represent valuable tools for studying the foregoing hypotheses. Indeed, first
      results indicate that mice with a deficit in GR expression show a depression-like
      behavioral phenotype as well as characteristic neuroendocrinological changes
      observed in depressive patients. Particularly, GR heterozygous mice with a 50%
      reduction of GR expression represent a model for combined effects of both genetic
      and environmental manipulations, since their depression-like behavior becomes
      only manifest after stress-exposure. Thus, the phenotype of this strain mimics
      the human situation in depressive disorders, in which individuals at risk are
      predisposed to develop depressive episodes after stress. It is currently less
      clear whether, and in which way, mice that overexpress GRs can serve as models
      for PTSD, or mimic at least specific aspects of the clinical syndrome. The latter
      strains have still to be subjected to specific tests analyzing conditioning and
      sensitization processes in fearful situations. So far, mice with compromised GR
      expression seem to be a good tool to further study molecular, pathophysiological
      and cellular/structural alterations that underlie specific behavioral features
      such as despair or helplessness. A major challenge is to decipher which signs and
      symptoms in patients correspond to these animal behavioral constructs, and to
      elucidate whether it is possible to gain insights from the animals' response to
      specific treatments for human therapy.

PMID- 18037008
TI  - Adrenal stress hormones, amygdala activation, and memory for emotionally arousing
      experiences.
AB  - Extensive evidence indicates that stress hormones released from the adrenal
      glands are critically involved in memory consolidation of emotionally arousing
      experiences. Epinephrine or glucocorticoids administered after exposure to
      emotionally arousing experiences enhance the consolidation of long-term memories
      of these experiences. Our findings indicate that adrenal stress hormones
      influence memory consolidation via interactions with arousal-induced activation
      of noradrenergic mechanisms within the amygdala. In turn, the amygdala regulates
      memory consolidation via its efferent projections to many other brain regions. In
      contrast to the enhancing effects on consolidation, high circulating levels of
      stress hormones impair memory retrieval and working memory. Such effects also
      require noradrenergic activation of the amygdala and interactions with other
      brain regions.

PMID- 18037009
TI  - Adult neurogenesis and systemic adaptation: animal experiments and clinical
      perspectives for PTSD.
AB  - The life-long persistence of neuron production in the adult mammalian central
      nervous system was established at the end of the 20th century and since then,
      intensive studies have been carried out to determine the biological role of
      neuronal turnover in the mature brain. To date, evidence has been found of
      involvement in learning/memory function and stress-related mental disorders. With
      a discussion of speculative link between impaired amygdala-relevant neurogenesis
      and PTSD in an animal model, we here review across species the functional
      significance of adult neurogenesis from the point of view of systemic adaptation.

PMID- 18037010
TI  - Commentary: behavioral phenotype.
AB  - PTSD arises by definition as a direct consequence of the experience of an acute
      severe stressor. The formation of traumatic memory and its extinction,
      sympathetic and adrenocortical stress systems activity in relation to individual
      vulnerability form the core of animal models for PTSD.

PMID- 18037011
TI  - Transgenerational transmission of cortisol and PTSD risk.
AB  - Parental posttraumatic stress disorder (PTSD) appears to be a relevant risk
      factor for the development of PTSD, as evidenced by a greater prevalence of PTSD,
      but not trauma exposure, in adult offspring of Holocaust survivors with PTSD,
      compared to children of Holocaust-exposed parents without PTSD. This paper
      summarizes recent neuroendocrine studies in offspring of parents with PTSD.
      Offspring of trauma survivors with PTSD show significantly lower 24-h mean
      urinary cortisol excretion and salivary cortisol levels as well as enhanced
      plasma cortisol suppression in response to low dose dexamethasone administration
      than offspring of survivors without PTSD. In all cases, neuroendocrine measures
      were negatively correlated with severity of parental PTSD symptoms, even after
      controlling for PTSD and even other symptoms in offspring. Though the majority of
      our work has focused on adult offspring of Holocaust survivors, recent
      observations in infants born to mothers who were pregnant on 9/11 demonstrate
      that low cortisol in relation to parental PTSD appears to be present early in the
      course of development and may be influenced by in utero factors such as
      glucocorticoid programming. Since low cortisol levels are particularly associated
      with the presence of maternal PTSD the findings suggest the involvement of
      epigenetic mechanisms.

PMID- 18037013
TI  - The functional neuroanatomy of PTSD: a critical review.
AB  - Neuroimaging provides an opportunity to understand core processes that mediate
      the experience of emotions in healthy individuals as well as dysregulation of
      these processes in conditions such as posttraumatic stress disorder (PTSD). The
      first decade of neuroimaging research produced symptom provocation, cognitive
      activation, and functional connectivity studies that highlighted the role of the
      medial prefrontal cortex (mPFC), amygdala, sublenticular extended amygdala
      (SLEA), and hippocampus, in mediating symptom formation in PTSD. There is a
      growing realization that a number of other psychological processes are relevant
      to PTSD, and they are emerging as a new focus of neuroimaging research. These
      include fear conditioning, habituation, and extinction; cognitive-emotional
      interactions; and self-related and social emotional processing. Neuroimaging
      findings are reviewed that suggest that the mPFC is implicated in a number of
      these processes. It is proposed that the mPFC plays a role in the
      "contextualization" of stimuli, and dysregulation of contextualization processes
      might play a key role in the generation of PTSD symptoms.

PMID- 18037012
TI  - Early care experiences and HPA axis regulation in children: a mechanism for later
      trauma vulnerability.
AB  - Post-traumatic stress disorder (PTSD) is associated with functional abnormalities
      of the hypothalamic-pituitary-adrenocortical (HPA) axis. Emerging evidence
      suggests that failures in social regulation of the HPA axis in young children
      manifested as neglectful or abusive care may play a role in shaping cortico
      limbic circuits involved in processing experiences threatening experiences
      encountered later in life. Low cortisol levels, particularly near the peak of the
      diurnal rhythm, have been reported in abused, neglected and deprived children.
      Thus early imprinting effects of parenting quality on the HPA system regulation
      may be one of the mechanisms causing heightened risk of PTSD in responses to
      later trauma. However there is also evidence that the altered patterns of
      cortisol production seen in the context of early adverse care are not permanent,
      and remit once the care children receive improves. What awaits study is whether
      periods of atypical cortisol levels and altered HPA function early in life, even
      if transient, impact brain development in ways that heighten vulnerability to
      PTSD in response to traumas experienced later.

PMID- 18037015
TI  - Commentary: biological findings in PTSD -- too much or too little?
AB  - Summarizing the contributions in this section of the book, this chapter addresses
      questions regarding the complex etiology of PTSD, and the relative strength of
      discernable biological indicators of the disorder. It outlines two major
      approaches to exploring the biology of the disorder and discusses the reason for
      the many non-replications of findings. It defines the constructs of
      multicausality, equifinality, and multifinality, and evaluates their main
      implication for studies of PTSD, namely that no biological signal can be properly
      appraised without taking into account its context. Such context, in PTSD,
      includes both concurring biological systems and regulatory mechanisms, and
      environmental-psychosocial input. Studies of gene expression of PTSD exemplify
      one way of studying the context of putative biological signals. The role of
      biological alterations as templates for responding to psychosocial challenges is
      discussed.

PMID- 18037016
TI  - Models of PTSD and traumatic stress: the importance of research "from bedside to
      bench to bedside".
AB  - The epidemiology and psychology of PTSD noted above is not often considered in
      neurobiological models of PTSD. Neurobiological models tend to focus on symptoms.
      This is an important perspective but it does not capture the brains total
      response to traumatic events. Similarly, neurobiologists have rarely used the
      extensive knowledge of animal behavioral responses to stress as a means to define
      the human stress phenomenology, looking for the human equivalent (rather than the
      other way around). The development of animal models for PTSD and other traumatic
      stress-related brain changes is an important part of advancing our
      neurobiological understanding of the disease process as well as recovery,
      resilience, and possible therapeutic targets. Animal models should address
      symptoms but also other aspects of PTSD that are seen in clinical care including
      the waxing and waning of symptoms, Understanding "forgetting", toxic exposure,
      failure to recover and how the neural systems fail rather than function are
      important perspectives on developing animal models. The cognitive process of
      identification is another important animal model to develop. Using these
      perspectives recent work has shown new avenues for understanding the trauma
      response in animal models and human brain tissue of individuals with PTSD. The 5
      HT2A receptor and p11 protein and associated regulators are avenues of new
      investigation that warrant study and consideration in models of PTSD.

PMID- 18037017
TI  - What is it that a neurobiological model of PTSD must explain?
AB  - PTSD is a complex disorder that involves far more than a fear response, and
      cannot be explained by a simple conditioning model. Both individual vulnerability
      and specific reactions during and after the trauma are involved in maintaining
      the disorder. A consideration of risk factors implicates the experience of being
      "overwhelmed" at the time of the trauma, accompanied by possible downregulation
      of the prefrontal cortex. Also important are reactions to symptoms post-trauma
      and specific strategies adopted to manage symptoms, such that there is a
      continuing inability to process trauma memories. An analysis of the
      characteristic forms of autobiographical memory in PTSD implicates two memory
      systems, one predominantly image-based and one predominantly verbal. These
      systems are likely to be differentially impacted by hormonal responses to extreme
      stress, leading to an imbalance in the representation of trauma in the two
      systems. Exposure to trauma reminders leads to retrieval competition between the
      two sets of memories, with retrieval of verbal memories able to inhibit
      inappropriate amygdala responses. Evidence to support this analysis is described,
      drawing on experimental studies of memory for trauma and a meta-analysis of
      memory for emotionally neutral information in PTSD. The implications for
      neurobiological studies of PTSD are discussed.

PMID- 18037014
TI  - Structural and functional plasticity of the human brain in posttraumatic stress
      disorder.
AB  - Posttraumatic stress disorder (PTSD) is associated with long-term changes in
      neurobiology. Brain areas involved in the stress response include the medial
      prefrontal cortex, hippocampus, and amygdala. Neurohormonal systems that act on
      the brain areas to modulate PTSD symptoms and memory include glucocorticoids and
      norepinephrine. Dysfunction of these brain areas is responsible for the symptoms
      of PTSD. Brain imaging studies show that PTSD patients have increased amygdala
      reactivity during fear acquisition. Other studies show smaller hippocampal
      volume. A failure of medial prefrontal/anterior cingulate activation with re
      experiencing of the trauma is hypothesized to represent a neural correlate of the
      failure of extinction seen in PTSD. The brain has the capacity for plasticity in
      the aftermath of traumatic stress. Antidepressant treatments and changes in
      environment can reverse the effects of stress on hippocampal neurogenesis, and
      humans with PTSD showed increased hippocampal volume with both paroxetine and
      phenytoin.

PMID- 18037018
TI  - Post-traumatic stress disorder in somatic disease: lessons from critically ill
      patients.
AB  - Post-traumatic stress disorder (PTSD) is a well-recognized complication of severe
      illness. PTSD has been described in patients after multiple trauma, burns, or
      myocardial infarction with a particularly high incidence in survivors of acute
      pulmonary failure (Acute Respiratory Distress Syndrome) or septic shock. Many
      patients with evidence of PTSD after critical illness have been treated in
      intensive care units (ICUs). Studies in long-term survivors of ICU treatment
      demonstrated a clear and vivid recall of different categories of traumatic memory
      such as nightmares, anxiety, respiratory distress, or pain with little or no
      recall of factual events. A high number of these traumatic memories from the ICU
      has been shown to be a significant risk factor for the later development of PTSD
      in long-term survivors. In addition, patients in the ICU are often treated with
      stress hormones like epinephrine, norepinephrine, or cortisol. The number of the
      above-mentioned categories of traumatic memory increased with the totally
      administered dosages of catecholamines and cortisol, and the evaluation of these
      categories at different time points after discharge from the ICU showed better
      memory consolidation with higher dosages of stress hormones administered.
      Conversely, the prolonged administration of beta-adrenergic antagonists during
      the recovery phase after cardiac surgery resulted in a lower number of traumatic
      memories and a lower incidence of stress symptoms at 6 months after surgery.
      Findings with regard to the administration of the stress hormone cortisol were
      more complex, however. Several studies from our group have demonstrated that the
      administration of stress doses of cortisol to critically ill patients resulted in
      a significant reduction of PTSD symptoms measured after recovery without
      influencing the number of categories of traumatic memory. This can possibly be
      explained by a cortisol-induced temporary impairment in traumatic memory
      retrieval that has previously been demonstrated in both rats and humans. ICU
      therapy of critically ill patients can serve as a stress model that allows the
      delineation of stress hormone effects on traumatic memory and PTSD development.
      This could also result in new approaches for prophylaxis and treatment of stress
      related disorders.

PMID- 18037019
TI  - Glucocorticoid-induced reduction of traumatic memories: implications for the
      treatment of PTSD.
AB  - Post-traumatic stress disorder (PTSD) is an anxiety disorder that can occur after
      a traumatic event such as military combat, terrorist attacks, or accidents. The
      disorder is characterized by traumatic memories that manifest as reexperiencing
      symptoms including daytime recollections, traumatic nightmares, or flashbacks in
      which components of the event are relived. These symptoms result from excessive
      retrieval of traumatic memories that often retain their vividness and power to
      evoke distress for decades or even a lifetime. We have reported previously that
      elevated glucocorticoid levels inhibit memory retrieval in animals and healthy
      human subjects. We therefore hypothesized that the administration of cortisol
      might also inhibit the retrieval of traumatic memories in patients with PTSD. In
      a recent pilot study we found the first evidence to support this hypothesis.
      During a 3-month observation period, low-dose cortisol (10 mg per day) was
      administered orally for 1 month to three patients with chronic PTSD using a
      double-blind, placebo-controlled, crossover design. In each patient investigated,
      there was a significant treatment effect with cortisol-related reductions in one
      of the daily-rated symptoms of traumatic memories without causing adverse side
      effects. Furthermore, we have reported evidence for a prolonged effect of the
      cortisol treatment. Persistent retrieval and reconsolidation of traumatic
      memories is a process that keeps these memories vivid and thereby the disorder
      alive. By inhibiting memory retrieval, cortisol may weaken the traumatic memory
      trace and thus reduce symptoms even beyond the treatment period. Future studies
      with more patients and longer treatment periods are required to evaluate the
      efficacy of cortisol treatment for PTSD.

PMID- 18037020
TI  - Commentary: synthesis and perspectives.

PMID- 18037021
TI  - Strain specific fear behaviour and glucocorticoid response to aversive events:
      modelling PTSD in mice.
AB  - "Pavlovian" fear conditioning in rodents allows studying the formation and
      extinction of fear memories. Male C57BL/6J but not BALB/c mice showed
      differential fear memory performance expressed as freezing and scanning behaviour
      for context and cue. Glucocorticoid stress hormones modulate the processing of
      fear-related stimuli. The augmented corticosterone response of BALB/c mice to
      conditioning and testing, therefore, might have contributed to the strain
      dependent formation of fear memories. We propose that modulation of extinction
      processes by glucocorticoids can be relevant in modelling anxiety disorders.

PMID- 18037022
TI  - Interaction of endogenous cortisol and noradrenaline in the human amygdala.
AB  - Animal studies show that glucocorticoid effects on memory depend on noradrenergic
      activation within an intact amygdala. Testing this model in humans is the subject
      of the present fMRI study. Healthy subjects watched emotional and neutral stimuli
      after having received a betablocker or placebo. Cortisol levels of all subjects
      were determined and served as a marker of the subject's (endogenous) cortisol
      level during the experiment. Viewing emotional pictures resulted in increased
      amygdala activation compared to neutral pictures and this effect was enhanced in
      subjects with a high versus low cortisol level under placebo condition.
      Betablockade with propranolol, lowering the noradrenergic level in the amygdala,
      disrupted this effect and apparently the interaction with cortisol. These data
      support the hypothesis that high endogenous cortisol levels at the time of
      encoding interact with noradrenergic activation in the amygdala in man.

PMID- 18037023
TI  - Corticosteroid hormones, synaptic strength and emotional memories: corticosteroid
      modulation of memory -- a cellular and molecular perspective.
AB  - Emotionally loaded and stressful events modulate cognitive performance. This
      modulation of cognitive performance is at least partially dependent on
      corticosteroid hormones that are released in high amounts during emotional or
      stressful events. Corticosterone both strengthens and suppresses cognitive
      performance and synaptic plasticity. These effects may critically depend on the
      timing of the stressful event and corticosteroid exposure with respect to the
      learning situation. Based on recent findings we propose a model in which
      corticosterone can rapidly enhance synaptic plasticity. Later, corticosterone may
      stabilize synaptic efficacy, possibly at the expense of reduced synaptic
      plasticity.

PMID- 18037024
TI  - Does trauma cause lasting changes in HPA-axis functioning in healthy individuals?
AB  - Although the majority of people who are exposed to traumatic events do not
      develop psychopathology, trauma has often been associated with increased
      vulnerability to psychiatric disorders. In addition, alterations in the HPA-axis
      have been demonstrated in patients with trauma-related psychiatric disorders. We
      hypothesize that trauma causes dysregulation of the HPA-axis. Therefore, we will
      compare HPA-axis functioning of traumatized and non-traumatized healthy
      individuals from the same gender and age from two categories: military and
      railroad personnel. In addition, a group of women with a history of childhood
      trauma was included. We will investigate for the putative role of attachment
      style and psychological resilience factors such as coping. In this article, we
      present the rationale for this study.

PMID- 18037025
TI  - Need for alternative ways of phenotyping of mood, anxiety, and somatoform
      disorders in biological research.
AB  - Variation in psychiatric symptomatology is continuous and does not coalesce into
      fairly well-defined categorical DSM-IV clusters. As a consequence, DSM-IV fails
      to meaningfully integrate information generated by neuroendocrine research.
      Continuous psychological dimensions selected for their predictiveness with
      respect to endophenotypes, as biological intermediate factors, are proposed to be
      the best ways in reaching an understanding of the causations in mood, anxiety,
      and somatoform disorders.

PMID- 18037026
TI  - The HPA-axis and immune function in burnout.
AB  - Burnout results from chronic work stress. Its complaints may be related to HPA
      axis disturbances or changes in immune function. In our studies the salivary
      cortisol awakening response, day-curve, and the suppressed level after
      dexamethasone intake were not different in a burned-out group compared to a
      control group. Nor was there a change in cortisol after a treatment period.
      Higher levels of DHEAS and the monocyte released anti-inflammatory cytokine IL-10
      were observed, however T-cell stimulated and dexamethasone inhibited cytokine
      release were not affected. The increased IL-10 level may be related to an
      increased sensitivity for infections.

PMID- 18037027
TI  - Elevated plasma corticotrophin-releasing hormone levels in veterans with
      posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) is associated with alterations in
      corticotrophin-releasing hormone (CRH) secretion. Plasma CRH levels, which are
      easily acquired, might serve as a predictor of hypothalamic CRH levels.
      Assessment of plasma CRH, adrenocorticotrophin hormone (ACTH), and cortisol
      levels in 31 veterans with PTSD, 30 traumatized veterans without PTSD matched on
      age, year, and region of deployment (traumacontrols), and 28 age-matched healthy
      controls (HCs) was carried out. Plasma CRH levels were higher in PTSD patients
      compared to both HCs (p=0.005) and traumacontrols (p=0.007). This led to our
      conclusion, that elevated plasma CRH levels are specifically related to PTSD and
      not to exposure to traumatic stress during deployment.

PMID- 18037028
TI  - Precuneal activity during encoding in veterans with posttraumatic stress
      disorder.
AB  - Impaired attention and memory are symptoms frequently associated with
      posttraumatic stress disorder (PTSD). Previous studies have identified fronto
      temporal alterations during encoding in patients with PTSD. We examine the role
      of the precuneus (located in the posteromedial parietal lobe) that is known to
      play a role in memory, but has largely been neglected in PTSD research. Male
      veterans with and without PTSD (n=12 per group) were subjected to fMRI during
      encoding of 12 neutral, non-trauma related word pairs. The precuneus was less
      activated in veterans with PTSD, which correlated significantly with the severity
      of PTSD. Like fronto-temporal regions the precuneus is differentially activated
      during memory formation in veterans with PTSD.

PMID- 18037029
TI  - Posttraumatic stress disorder with secondary psychotic features: neurobiological
      findings.
AB  - The neurobiological knowledge on the potentially new diagnostic entity
      "posttraumatic stress disorder with secondary psychotic features" (PTSD-SP) is
      reviewed. Studies published between 1980 and 2006 were traced focussing on adult
      patients suffering from this "syndrome". Studies on cortisol, corticotrophin
      releasing hormone, dopamine beta-hydroxylase, smooth pursuit eye movements and
      psychopharmacology are described and potential pathophysiological mechanisms
      briefly discussed. More research is needed to validate the nosological status of
      PTSD-SP in order to promote neurobiological research and adequate therapeutic
      interventions.

PMID- 18037030
TI  - Neuroendocrine dysregulations in sexually abused children and adolescents: a
      systematic review.
AB  - Several studies provided evidence for neuroendocrine dysregulations in adults
      with a history of child sexual abuse. This review focuses on neuroendocrine
      studies in sexually abused children and adolescents, dating from January 1, 1990
      to January 1, 2007 and obtained from a systematic Medline Indexed literature
      search to identify endocrine correlates of child sexual abuse. Results from
      studies on hypothalamic-pituitary-adrenal axis (re)activity showed to be
      inconclusive. Studies on the sympathetic nervous system provided evidence for a
      higher baseline activity of this system in sexually abused children and
      adolescents. Factors contributing to divergent outcomes will be discussed and
      suggestions for future research will be presented.

PMID- 18037031
TI  - Volume of discrete brain structures in complex dissociative disorders:
      preliminary findings.
AB  - Based on findings in traumatized animals and patients with posttraumatic stress
      disorder, and on traumatogenic models of complex dissociative disorders, it was
      hypothesized that (1) patients with complex dissociative disorders have smaller
      volumes of hippocampus, parahippocampal gyrus, and amygdala than normal controls,
      (2) these volumes are associated with severity of psychoform and somatoform
      dissociative symptoms, and (3) patients who recovered from dissociative identity
      disorder (DID) have more hippocampal volume that patients with florid DID. The
      preliminary findings of the study are supportive of these hypotheses.
      Psychotherapy for dissociative disorders may affect hippocampal volume, but
      longitudinal studies are required to document this potential causal relationship.

PMID- 18037032
TI  - Epilogue: neuroendocrinology of PTSD.

PMID- 18037033
TI  - Quantitative determination of paraquat in meconium by sodium borohydride-nickel
      chloride chemical reduction and gas chromatography/mass spectrometry (GC/MS).
AB  - The objective of this study was to develop a procedure for the GC/MS assay of
      paraquat in meconium as a biomarker of fetal exposure to paraquat. The method
      involved a sodium borohydride-nickel chloride reduction procedure, liquid-liquid
      extraction of the perhydrogenated product, concentration, and GC/MS assay. The
      method demonstrated good overall recovery (102.56%) with %CV (inter-assay) of
      less than 13%, and a limit of detection of 0.0156microg/g. Analysis of meconium
      samples from a study population in the Philippines (n=70) showed a 2.8%
      prevalence of fetal exposure to paraquat.

PMID- 18037036
TI  - Operative treatment of coronal craniosynostosis: 20 years of experience.
AB  - BACKGROUND: To investigate the effect on and risk in coronal synostosis surgery
      of fronto-orbital advancement. METHODS: One hundred sixty-five cases of coronal
      synostosis were retrospectively reviewed, including their clinical
      manifestations, computed tomography scans, operations, operative complications,
      and follow-up results. RESULTS: Of the 165 cases, 111 were male and 54 were
      female, with a mean age of 12.1 months. Unilateral coronal synostosis was
      encountered in 38 cases and bilateral in 127, 45 of which were accompanied by
      Crouzon syndrome. All cases underwent fronto-orbital advancement. After the
      operation, 1 patient died from intracranial hemorrhage and 5 developed
      craniospinal fluid leak. No reoperation was necessary for coronal synostosis
      relapse in a follow-up study from 3 months to 5 years. CONCLUSION: Fronto-orbital
      advancement is an effective and safe technique for coronal synostosis. However,
      longer follow-up is required to rectify the final functional and aesthetic
      results of craniofacial architecture.

PMID- 18037037
TI  - Violent head trauma in China: report of 2254 cases.
AB  - BACKGROUND: The occurrence of violent trauma has recently increased, and it has
      become both a social and medical problem in China. We are the first to explore
      violent head trauma in China. METHODS: Patients with violent head trauma were
      taken from all hospitalized patients with head trauma from January 2001 to
      December 2006 admitted to 11 hospitals in China. The rate, causes, age, sex,
      injury severity (GCS score), CT findings, management, outcome, and complications
      of patients with violent head trauma were retrospectively analyzed. RESULTS: Two
      thousand two hundred fifty-four (9.46%) patients with violent head trauma were
      found among a total of 23816 hospitalized patients with head trauma at 11
      hospitals. Violent head trauma was caused by blunt objects (n = 1260, 55.90%),
      sharp/cutting instruments (n = 271, 12.02%), gunshots (n = 10, 0.44%), and others
      (n = 713, 31.63%). Violent head trauma was more likely to be found men (n = 1890,
      83.85%) and in persons aged 21 to 40 years (n = 1216, 53.95%). In 2254 patients
      with violent head trauma, scalpel injury was seen in 1277 cases, skull fracture
      in 786 cases, cerebral contusion in 285 cases, and intracranial hematomas in 898
      cases. Five hundred eighty-nine (26.13%) patients had body violent trauma besides
      violent head trauma. A GCS score of 13 to 15 was found in 1869 (82.92%) patients,
      9 to 12 in 166 (7.36%), and 8 or less in 219 (9.72%). One thousand forty-two
      patients got surgical treatment, and another 1212 received medical management.
      One thousand nine hundred thirty-one (85.67%) patients had good recovery, 141
      (6.47%) had moderate deficits, 36 (1.65%) had severe deficits, 7 (0.32%) had PVS,
      63 (2.89%) died, and for the other 76, records were lost. CONCLUSIONS: Violent
      head trauma is certainly both a social and medical problem now, which indicates
      that violence should be controlled and that the human right of social safety
      needs to be improved in China.

PMID- 18037039
TI  - Myxoma of the cranial base.
AB  - BACKGROUND: In 1871, Virchow described a type of tumor, which he named myxoma,
      which had a similar appearance to mucinous tissue of the umbilical cord. Myxoma
      occurs most frequently in the heart and jawbone, less frequently in the temporal
      bone mastoideum, and rarely in the cranial base of the brain. From an etiologic
      perspective, intracranial myxoma is divided into either primary or secondary
      induction. The majority of primary myxomas are found at the skull base, whereas
      secondary intracranial myxomas are mainly caused by metastatic tumor emboli from
      the cardiac myxomas; the emboli may also transfer to cerebrovascular endothelium
      to cause fusiform aneurysm. From October 1983 until November 2005, 23 patients
      with cranial base myxoma, as confirmed by pathology, were treated in the
      neurosurgery department of Beijing Tiantan Hospital. Few data are available from
      published literature on diagnosis and treatment of cranial base myxoma;
      therefore, the aim of this study was to describe a large series of patients
      undergoing treatment for cranial base myxoma and to analyze and discuss clinical
      manifestations, diagnosis, and treatment of cranial base myxoma. METHODS: A
      retrospective analysis was undertaken of 23 cases of cranial base myxoma, as
      confirmed by pathologic diagnosis. The review included all patients treated
      between October 1983 and November 2005. Among the 23, 8 patients received
      adjuvant radiotherapy after surgery. Postsurgical outcome data were unavailable
      for 12 patients. The mean duration of follow-up in the remaining 11 patients was
      64.5 months. RESULTS: Tumors were commonly located at the middle fossa,
      parasellar, and jugular regions with characteristic calcification demonstrated
      with magnetic resonance imaging. Patients presented with headache and multiple
      lesions of the cranial nerves. Surgical approaches were variable and selected
      according to tumor locations. Partial resections were achieved in 16 cases and
      total resections in 7 cases. Complete relief of clinical symptoms was achieved in
      2 cases, unchanged in 11 cases, and aggravated in 9 cases. During the period of
      follow-up, remission was gained in 6 cases and tumor recurrence in 4 patients; 1
      patient died. CONCLUSIONS: Cranial base tumors are difficult to diagnose. By
      clinical features and neuroradiological findings, it is hard to distinguish
      myxoma from chondroma and chordoma in this region. Treatment results are seldom
      encouraging; the goal of complete surgical resection is rarely achieved, and the
      outcome of radiotherapy is not very successful.

PMID- 18037040
TI  - An intrasellar rhabdomyosarcoma misdiagnosed as pituitary adenoma.
AB  - BACKGROUND: Rhabdomyosarcoma is a malignant tumor of the skeletal muscle cells.
      Those tumors mainly affect children and arise in primitive fetal mesenchyme even
      at sites that do not contain skeletal muscle. However, very few intracranial
      rhabdomyosarcomas have been reported. No previous case of primary intrasellar
      rhabdomyosarcoma except for 1 case has been reported in the literature. CASE
      DESCRIPTION: A 44-year-old woman presented with fatigue and diplopia associated
      with amenorrhea and galactorrhea. Visual field evaluation revealed a superior
      temporal deficit in both eyes. A right afferent pupillary defect was present.
      Magnetic resonance imaging revealed an intrasellar tumor with suprasellar
      extension. The tumor involved the sella turcica and right cavernous sinus. The
      patient was preoperatively diagnosed as pituitary adenoma, which was confirmed
      pathologically as rhabdomyosarcoma after the operation. CONCLUSIONS: Our findings
      suggest that rhabdomyosarcoma should be considered in the differential diagnosis
      of a primary intrasellar neoplasm.

PMID- 18037043
TI  - Surgical management of anterior clinoidal meningiomas: a 26-case report.
AB  - BACKGROUND: Resection of anterior clinoidal meningiomas remains a major
      neurosurgical challenge. We determine the surgical technique for removal of tumor
      and improvement of patient's outcome. METHODS: A retrospective analysis was
      performed on 26 consecutive patients with anterior clinoidal meningiomas who
      underwent surgical resection at the Department of Neurosurgery, Renji Hospital,
      from January 1999 to August 2006. All patients had surgery through the pterional
      or extended pterional approach. Microvascular Doppler probe was used to protect
      the internal carotid artery and its branching arteries during dissection of the
      tumor. Twenty-two of them had severe visual deficits preoperatively. The follow
      up period ranged from 3 to 36 months (22.3 +/- 8.8 months). RESULTS: In this
      series, Simpson grade II resection in 16 cases (61.5%), Simpson grade III
      resection in 4 cases (15.4%), Simpson grade IV resection in 6 cases (23.1%) were
      achieved. Sixteen of the patients with preoperative visual impairment experienced
      significant improvement. No patients died. There was no evidence of tumor
      recurrence during follow-up. CONCLUSIONS: In the majority of patients, surgery is
      still the first choice for total resection of the tumors without major
      complications. Protection of nerves and blood vessels must be a priority concern
      during removal of tumors.

PMID- 18037044
TI  - Evidence on the impact of child labor on child health in Indonesia, 1993--2000.
AB  - Despite an abundant literature on child labor in developing countries, few papers
      have attempted to investigate the consequences of child labor on health. This
      paper explores whether child labor affects child health using data from the
      Indonesian Socio-Economic Surveys during the 1990s. For our empirical analysis,
      we restrict our attention to children currently enrolled in school and we use
      several discrete indicators for health. Our results show that child labor is
      associated negatively with health. We obtain this result by introducing labor
      participation as an exogenous covariate in the different health equations.
      Similar results are found once the work decision is instrumented.

PMID- 18037045
TI  - Wanted: a base of evidence.

PMID- 18037046
TI  - A six year evaluation of cracked teeth diagnosed with reversible pulpitis:
      treatment and prognosis.
AB  - The purpose of this investigation was to report on the clinical outcomes of
      cracked teeth diagnosed with reversible pulpitis (RP). Eight thousand one hundred
      seventy-five patients referred for evaluation and treatment during a 6-year
      period had medical and dental histories, radiographs, pulpal and periapical
      diagnosis, periodontal probings, direct identification of crack(s) with
      transillumination, and biting responses on various cusps recorded. All data were
      stored daily in a database. All cases were treatment planned according to the
      pulpal and periapical diagnosis. Cases with RP were treatment planned for crowns
      only, regardless of periapical diagnosis. All patients were recalled at 1 year
      unless root canal treatment was needed before the anniversary. Results indicated
      that cracks were identified in 9.7% (796 of 8175) of all teeth evaluated during
      this time period. Of 127 patients specifically diagnosed with RP, 27 converted to
      irreversible pulpitis (N = 21) in 58 days or to necrotic pulp (N = 6) in 149
      days. To date, none of the original remaining 100 cases of RP have required root
      canal treatment. The outcomes of this study suggest that if a marginal ridge
      crack is identified early enough in teeth with a diagnosis of RP and a crown is
      placed, root canal treatment will be necessary in about 20% of these cases within
      a 6-month period.

PMID- 18037047
TI  - Vascular endothelial growth factor receptor-2 expression in the pulp of human
      primary and young permanent teeth.
AB  - The purpose of this study was to evaluate the expression of vascular endothelial
      growth factor receptor-2 (VEGFR-2) in endothelial cells within the dental pulp of
      human primary and young permanent teeth and the spatial distribution of VEGFR-2
      positive cells. Nine sound primary teeth and 4 sound young permanent teeth were
      evaluated by immunohistochemistry with a human anti-VEGFR-2 antibody. Stained
      tissue sections were analyzed qualitatively under light microscopy. Here we
      observed that endothelial cells of both primary and permanent teeth showed
      positive immunostaining for VEGFR-2. Notably, VEGFR-2-positive cells in the
      primary teeth tended to be found close to the subodontoblastic layer, whereas the
      spatial distribution of VEGFR-2 immunostaining in the permanent teeth was more
      uniform. In conclusion, VEGFR-2 was expressed in the microvascular endothelial
      cells of both primary and young permanent teeth, which suggests that these cells
      are capable of responding to the morphogenetic and survival signals mediated by
      VEGF.

PMID- 18037048
TI  - The correlation between serum immunoglobulin A and immunoglobulin G levels and
      the presence of Treponema denticola in human periapical lesions.
AB  - The aim of this study was to compare the serum immunoglobulin A (IgA) and
      immunoglobulin G (IgG) levels and the presence of Treponema denticola in the root
      canals in a group of teeth with/without periapical lesion. A total of 66 children
      aged 8 to 13 years old were involved in this study. Five milliliters of blood
      samples were taken to detect the serum IgA and IgG levels. Sixty-six endodontic
      samplings were also obtained to determine the presence of T. denticola by
      polymerase chain reaction. The presence of T. denticola between the groups
      with/without periapical lesion was statistically significant (p = 0.026). A
      significant negative correlation was found between serum IgG and IgA levels and
      the presence of T. denticola (p = 0.023 and 0.038, respectively). This study may
      support the hypothesis that the presence of T. denticola in the root canals is
      mainly related to the periapical lesions, and the higher levels of serum IgG and
      IgA levels may protect against T. denticola.

PMID- 18037049
TI  - Bacterial DNA persists for extended periods after cell death.
AB  - The fate of DNA from bacteria that infect the root canal but cannot survive is
      currently unknown, yet such information is essential in establishing the validity
      of polymerase chain reaction (PCR)-based identification methods for root canal
      samples. This in vitro study tested the hypothesis that PCR-detectable DNA from
      dead bacteria might persist after cell death and investigated the efficiency of
      sodium hypochlorite (NaOCl) as a field decontamination agent. Using heat-killed
      Enterococcus faecalis, the persistence of DNA encoding the 16S rRNA gene was
      monitored by PCR. While most probable number analysis showed an approximate 1000
      fold decay in amplifiable template, E. faecalis DNA was still PCR-detectable 1
      year after cell death. NaOCl (1%) eliminated amplifiable DNA within 60 seconds of
      exposure. Our findings also disclosed a previously overlooked problem of
      concentration-dependent inhibition of the PCR reaction by thiosulfate-inactivated
      NaOCl. These results highlight the challenges of reliably identifying the
      authentic living root canal flora with PCR techniques.

PMID- 18037050
TI  - Effect of tissue fluids on hydrophobicity and adherence of Enterococcus faecalis
      to dentin.
AB  - This in vitro study was carried out to determine (1) the hydrophobicity of
      selected oral bacteria, (2) the influence of growth media (saliva and serum) and
      mode of growth (planktonic or biofilm) on the hydrophobicity of Enterococcus
      faecalis, and (3) the influence of growth media and conditioning fluids on the
      adherence of E. faecalis to dentin. The ability to bind to a hydrocarbon phase
      (xylene) was used as an index of relative hydrophobicity of cells. Fluorescent
      microscopy-based technique was used to assay the bacterial adherence to dentin.
      Results showed that bacteria involved in the primary stage of oral biofilm
      formation such as Streptococcus mutans, Fusobacterium nucleatum, and
      Porphyromonas gingivalis are relatively more hydrophobic than E. faecalis. The
      hydrophobicity of E. faecalis was significantly increased during starvation and
      biofilm mode of growth (p < .05). The adherence of E. faecalis to dentin was
      appreciably increased after starvation and when dentin was conditioned with
      saliva. It was observed that surface conditioning of dentin with saliva and
      starvation can enhance the adherence of E. faecalis to dentin. The findings from
      this study indicated that the coronal leakage of saliva and the physiologic state
      of microbes might play an important role in the adherence and biofilm formation
      of bacteria to root canal dentin.

PMID- 18037051
TI  - In vitro evaluation of the cleansing working time and analysis of the amount of
      gutta-percha or Resilon remnants in the root canal walls after instrumentation
      for endodontic retreatment.
AB  - The present study assessed the obturation removal and reinstrumentation working
      time of canals filled with Resilon/Real Seal in comparison with canals filled
      with gutta-percha/AH Plus. Thirty human extracted canines were instrumented. In
      group 1 (n = 15) root canals were filled with Resilon/Real Seal and in group 2 (n
      = 15) with gutta-percha/AH Plus sealer. The obturations were removed from both by
      using chloroform and irrigation with 2.5% NaOCl, and the canals were manually
      reinstrumented. The teeth were radiographically analyzed. Specimens without
      obturation material remnants visible in the radiographic examination were
      selected for analysis under scanning electron microscopy. The Resilon/Real Seal
      system was removed in greater quantities from the canal walls compared with the
      gutta-percha cones and the AH Plus cement. Time was not a significant factor.
      Under scanning electron microscopy analysis, the teeth presented material
      remnants in the 3 analyzed thirds. Resilon was better removed from the canal than
      the gutta-percha cones and the AH Plus.

PMID- 18037052
TI  - Sealing ability of white and gray mineral trioxide aggregate mixed with distilled
      water and 0.12% chlorhexidine gluconate when used as root-end filling materials.
AB  - This in vitro study used dye penetration to compare the sealing ability of white
      and gray mineral trioxide aggregate mixed with distilled water and 0.12%
      chlorhexidine gluconate when used as root-end filling materials. Ninety-six
      single-rooted human teeth were cleaned, shaped, and obturated with gutta-percha
      and AH26 root canal sealer. The apical 3 mm of each root was resected, and 3-mm
      deep root-end cavity preparations were made. The teeth were randomly divided into
      4 experimental groups, each containing 20 teeth, and 2 negative and positive
      control groups, each containing 8 teeth. Root-end cavities in the experimental
      groups were filled with the experimental materials. After decoronation of the
      teeth and application of nail polish, the teeth were exposed to India ink for 72
      hours and longitudinally sectioned, and the extent of dye penetration was
      measured with a stereomicroscope. Statistical analysis showed that there were no
      significant differences among the 4 experimental groups.

PMID- 18037053
TI  - Effect of environment on low-cycle fatigue of a nickel-titanium instrument.
AB  - This study examined the low-cycle fatigue (LCF) behavior of a nickel-titanium
      (NiTi) engine-file under various environmental conditions. One brand of NiTi
      instrument was subjected to rotational-bending fatigue in air, deionized water,
      sodium hypochlorite, or silicone oil. The curvature of each instrument, diameter
      of the fracture cross-section, and the number of rotations to failure were
      determined. The strain-life relationship in the LCF region was examined by using
      one-way analysis of variance, and the number of crack origins with chi2, for
      differences between groups. The results showed a linear relationship, on
      logarithmic scales, between the LCF life and the surface strain amplitude;
      regression line slopes were significantly different between noncorrosive (air,
      silicone oil) and corrosive (water, hypochlorite) environments (P < .05), as well
      as number of crack origins (P < .05). Hypochlorite was more detrimental to
      fatigue life than water. In conclusion, environmental conditions significantly
      affect the LCF behavior of NiTi rotary instruments. Fatigue testing of NiTi
      engine-files should be in a service-like environment.

PMID- 18037054
TI  - In vitro evaluation of a Ceramicrete-based root-end filling material.
AB  - Ceramicrete is an impervious inorganic binder widely used for encapsulating
      radioactive and hazardous wastes. This study evaluated the feasibility of using a
      radiopaque Ceramicrete-based material for root-end fillings. Apical seals of root
      end preparations filled with Super EBA (Harry J. Bosworth Co, Skokie, IL), White
      ProRoot MTA (Dentsply Tulsa Dental Specialties, Tulsa, OK), or Ceramicrete-D were
      evaluated using a computerized fluid filtration approach after the fillings were
      immersed in phosphate-containing fluid (PCF). The Ceramicrete-D fillings
      exhibited significantly (P < 0.05) better seals than the other two commercially
      available, frequently advocated root-end-filling materials. Scanning electron
      microscopy and x-ray diffraction of Ceramicrete-D after setting revealed a
      relatively nonporous KMgPO4.6H2O matrix that binds other incompletely reacted and
      new reaction phases such as CaHPO4.2H2O. Polished dentin slabs filled with
      Ceramicrete-D and immersed in PCF for 72 hours revealed depositions of acicular
      shaped, apatite-like crystallite clusters on the material surface as the pH of
      the PCF increased with immersion time. The experimental Ceramicrete-based
      material is potentially bioactive in the presence of PCF.

PMID- 18037055
TI  - Apical accuracy of two apex-locating handpieces in root canal retreatments of
      root-end resected teeth.
AB  - We aimed to evaluate the accuracy of 2 apex locator integrated endodontic motors
      during retreatment of root-end resected teeth by using 40 extracted incisor
      teeth. The apical 3 mm of the roots were resected, and the root lengths were
      recorded as resected length of the roots. Forty roots were randomly divided into
      2 groups of 20 to evaluate the 2 handpieces, Tri Auto ZX and TCM Endo V. The
      working lengths measured during the auto reverse function and during the
      electronic apex locator function with Tri Auto ZX and TCM Endo V were recorded
      and compared with resected length of the roots. The repeated measures analysis of
      variance was used for statistical analyses. Electronic apex locator functions of
      both devices might be used for apical accuracy, but the auto reverse functions
      might not be useful to 0.0-mm accuracy in retreatment procedures of root-end
      resected teeth.

PMID- 18037056
TI  - An in vitro comparison of microleakage between Resilon and gutta-percha with a
      fluid filtration model.
AB  - This investigation compared microleakage of teeth obturated with gutta-percha and
      teeth obturated with Resilon by using a fluid filtration model. Forty-six human,
      single-rooted, mandibular premolars were studied. Teeth were randomly assigned to
      2 experimental groups of 21 teeth each, designated as group G (gutta-percha) and
      group R (Resilon). Two control groups, both containing 2 teeth, served as
      positive and negative controls. Group G, gutta-percha and AH 26 sealer, and group
      R, Resilon and Epiphany sealer, were obturated by using warm vertical
      condensation. The specimens were tested for microleakage with an in vitro fluid
      filtration apparatus at 10 psi at 4 intervals: 1, 7, 30, and 90 days. A two-way
      repeated measures analysis of variance model with fixed effects for group, time,
      and group by time interaction was used to analyze microleakage data. This study
      demonstrated that canals obturated with Resilon and Epiphany sealer leaked
      statistically less than canals obturated with gutta-percha and AH 26 sealer at
      day 1 (P < .0014), day 7 (P < .0002), day 30 (P < .0015), and day 90 (P < .0170).
      The mean fluid microleakage for both group G and group R increased from day 1 to
      day 90. The results showed that Resilon is a suitable replacement for gutta
      percha as a root canal filling material on the basis of its increased resistance
      to fluid microleakage.

PMID- 18037057
TI  - Cytotoxic effects of four different endodontic materials in human periodontal
      ligament fibroblasts.
AB  - The purpose of this study was to compare the cytotoxicity, induced apoptosis
      and/or necrosis, and apoptotic mechanisms in human periodontal ligament (PDL)
      fibroblasts treated with four different endodontic materials: White ProRoot
      mineral trioxide aggregate (MTA) (MTA/Dentsply; Tulsa Dental, Memphis, TN),
      Diaket (ESPE, Seefeld, Germany), Endion (VOCO, Cuxhaven, Germany), and CYMED 8410
      (NANO, Kaohsiung, Taiwan). The effects of these four materials on the viability
      of PDL fibroblasts were determined by MTT (3-(4,5-dimethyl-thiazoyl)-2,5-diphenyl
      SH-tetrazolium bromide) assay. Apoptotic pathways were evaluated via several
      mechanisms. Exposure to MTA for 24, 48, and 72 hours resulted in no significant
      differences in MTT reduction and viable cell number compared with controls.
      However, treatment of PDL fibroblasts with Diaket, Endion, and CYMED 8410 for 24,
      48, and 72 hours resulted in cytotoxicity with MTT and a reduction of viable cell
      number with trypan blue dye exclusion test compared with controls (from p < 0.05
      to p < 0.001). Annexin V-FITC/PI staining showed that Diaket, Endion, and CYMED
      8410 induced higher percentages of apoptosis and/or necrosis than in controls
      (45.6%, 25.5%, and 6.3%, respectively). Results of cell-cycle analyses were
      concordant with annexin V-FITC/PI staining findings. These results suggest that
      MTA is a very biocompatible filling material. However, Diaket, Endion, and CYMED
      8410 are toxic to PDL fibroblasts in vitro. The main form of cell death induced
      by these filling materials was determined to be apoptosis and/or necrosis.

PMID- 18037058
TI  - A comparative study of the effects of two nickel-titanium preparation techniques
      on root canal geometry assessed by microcomputed tomography.
AB  - The present study was conducted with the aim of evaluating and comparing the
      effects of a new Hero group (Endoflare, Hero-shaper, and Hero-apical; Micro-Mega,
      Besancon, France) and Protaper Ni-Ti rotary instruments (Dentsply/Maillefer,
      Ballaigues, Switzerland) on root canal geometry in extracted human teeth using
      microcomputed tomography (muCT). Twenty-two mesial root canals of mandibular
      first molars were randomly divided into two groups. Canals were scanned before
      and after preparation with both systems. Cross-sectional images of each canal
      were obtained at 2-mm intervals. Differences in canal roundness, cross-sectional
      area, perimeter of each canal before and after instrumentation, and the extent of
      root canal transportation were calculated using image analysis software. There
      was no difference between the two rotary systems in regards to working time. Both
      systems create a similar round shape after instrumentation regardless of the
      initial root canal's shape. The Hero instruments showed a greater cutting
      efficiency compared with the ProTaper at the levels of 8 mm, 6 mm, and 4 mm but
      not at the level of 2 mm. On the other hand, the ProTaper seems to have a similar
      cutting efficiency at all levels. However, the ProTaper showed a tendency toward
      apical transportation. Under the conditions of the present study, both
      preparation techniques prepared the canals rapidly with a sufficient round shape.
      Despite that, it seems that there is a great potential for the improvement of
      shaping ability of rotary instruments. Hybrid instrumentation techniques should
      be evaluated by future studies in order to provide better results regarding the
      shaping ability of rotary instruments.

PMID- 18037059
TI  - Assessment of the deviation after biomechanical preparation of the coronal,
      middle, and apical thirds of root canals instrumented with three HERO rotary
      systems.
AB  - The aim of the present study was to assess the risk of deviation of the root
      canals prepared by 3 HERO rotary systems, used solely or in association, by means
      of preoperative and postoperative imaging of a cross-section of their coronal,
      middle, and apical thirds. Fifty mesiobuccal canals of human first molars were
      randomly divided into 5 groups of 10 specimens each: group A, HERO 642; group B,
      HERO 642 + HERO Apical; group C, HERO Shaper; group D, HERO Shaper + HERO Apical;
      group E (control), NitiFlex files. Fisher exact test showed that the differences
      between the percentages of the presence of deviation and the differences observed
      between the proportions of instrumented and noninstrumented walls were not
      statistically significant. No system presented absolute effectiveness, because
      each of them produced morphologic changes and failed to instrument all the walls
      of the root canals. A level of significance of .05 was adopted.

PMID- 18037060
TI  - Regional push-out bond strength and coronal microleakage of Resilon after
      different light-curing methods.
AB  - The purpose of this study was to assess the push-out bond strength and coronal
      microleakage of the Epiphany (Pentron Clinical Technologies, Wallingford, CT) +
      Resilon (Resilon Research LLC, Madison, CT) obturation system with respect to
      different photoactivation methods used. Roots of human maxillary central incisors
      (n = 60) were prepared with 0.06 taper nickel-titanum rotary files to size 30.
      After application of the Epiphany sealer, the roots were obturated with Resilon
      cones. The specimens were randomly assigned into three groups (n = 10/group)
      according to the light-curing unit (LCU) used from the coronal aspect: (1) quartz
      tungsten-halogen/40 seconds, (2) light-emitting diode/20 seconds, and (3) plasma
      arc/6 seconds. Thereafter, 2-mm thick horizontal sections (n = 3) were obtained
      from each specimen from the coronal to apical direction and subjected to push-out
      test at a crosshead-speed of 1mm/min. Failure modes were assessed quantitatively
      under a stereomicroscope and morphologically under a scanning electron
      microscope. The remaining 30 roots were used for the dye-leakage assessments.
      Both the type of LCU and the level of sectioning had significant effects on bond
      strength. The following statistical ranking was obtained for bond strength
      values: quartz-tungsten-halogen > light-emitting diode > plasma arc. Coronal
      microleakage of specimens cured with the plasma arc was significantly greater
      than those of other groups (p < 0.05).

PMID- 18037061
TI  - Cyclic fatigue of EndoSequence and K3 rotary files in a dynamic model.
AB  - The cyclic fatigue resistance of K3 and EndoSequence files was compared by
      rotating files against a highly polished surface inclined at 15 degrees to the
      horizontal. For each brand, files with a 25 tip in .04 and .06 taper and files
      with a 40 tip in .04 and .06 taper were tested at both 300 and 600 rpm. A 3-mm
      axial movement simulated a clinical pecking motion at 1 cycle per second. The
      number of rotations to failure was calculated and analyzed by using analysis of
      variance and Independent Student's t tests, with results confirmed by
      nonparametric Mann-Whitney U tests with a Bonferroni correction. At both 300 and
      600 rpm, K3 files exhibited statistically significantly more cycles to fracture
      than their EndoSequence counterparts with the same tip size and taper. Scanning
      electron microscopy images demonstrated surface features consistent with fracture
      due to cyclic fatigue. In this model, file design appeared to be the most
      important determinant of cyclic fatigue resistance.

PMID- 18037062
TI  - Disinfection of dentinal tubules with 2% chlorhexidine, 2% metronidazole,
      bioactive glass when compared with calcium hydroxide as intracanal medicaments.
AB  - Thorough disinfection of the root canal system is essential for the success of
      root canal therapy. This requires the use of an intra-canal medicament.
      Enterococcus faecalis is the most frequently found species in
      persistent/secondary intracanal infection associated endodontic treatment
      failure. This study evaluates the disinfection of dentinal tubules using 2%
      chlorhexidine gel, 2% metronidazole gel, bioactive glass (S53P4) in comparison
      with calcium hydroxide. The antibacterial efficacy of the four medicaments
      against Enterococcus faecalis was assessed in vitro using extracted premolar
      teeth at the depths of 200 microm and 400 microm. The overall percentage
      inhibition of bacterial growth (at 200 microm and 400 microm depth) was 100% with
      2% chlorhexidine gel. The inhibition of growth was moderate with 2% metronidazole
      gel (86.5%), followed by bioactive glass (62.8%) and calcium hydroxide (58.5%).
      It can be concluded from the present study that 2% chlorhexidine gel alone was
      most effective against E. faecalis when compared to other medicaments tested.

PMID- 18037063
TI  - Influence of previous angular deformation on flexural fatigue resistance of K3
      nickel-titanium rotary instruments.
AB  - Several studies have evaluated the influence of torsion and bending loads on the
      mechanical resistance of nickel-titanium instruments. The aim of the present
      study was to analyze the influence of previous angular deformation on K3 files
      resistance to flexural fatigue. New files and files previously submitted to
      different angular deformation were tested for flexural fatigue, and the number of
      cycles to fracture was compared. The results indicated that as the angular
      deformation increases, the number of cycles attained under flexural fatigue
      condition decreases. A reduction of fatigue resistance was registered even when a
      significant plastic deformation was not imposed. From the obtained results, it
      may be suggested that the sequential loading, including torsion and flexural
      fatigue, can be responsible for instrument separation during clinical practice.
      Successive torsion overloads, occurring together with flexural fatigue, reduce
      the mechanical resistance of nickel-titanium files.

PMID- 18037064
TI  - Mandibular first molar with four distal canals.
AB  - A mandibular first molar with more than four canals is an interesting example of
      anatomic variations, especially when four of these canals are located in distal
      roots. This report describes a case of a mandibular first molar with six canals
      (two mesial and four distal canals in two distal roots). The canals were equipped
      with a K-file and irrigated with NaOCl (5.25%) and normal saline as the final
      irrigant. The canals were filled laterally with gutta percha and AH26 sealer (De
      Trey, Dentsply, Switzerland). This case shows a rare anatomic configuration and
      points out the importance of looking for additional canals.

PMID- 18037065
TI  - Inferior alveolar nerve damage because of overextended endodontic material: a
      problem of sealer cement biocompatibility?
AB  - Damage to the inferior alveolar nerve is a relatively infrequent complication in
      dental practice. When root canal treatment of a lower molar or premolar surpasses
      and/or overextends beyond the apical foramen and invades the periapical zone, the
      foreign material introduced within such a sensitive anatomical space may
      mechanically or even chemically affect the inferior alveolar nerve. We describe a
      case of endodontic treatment of a permanent right lower first molar in which the
      sealer cement overextended in large amounts and damaged the right inferior
      alveolar nerve. The condition reverted a few months after the surgical removal of
      the material. Evaluation of the removed material, using powder x-ray diffraction
      and scanning electron microscopy with coupled dispersive energy spectroscopy,
      showed it to consist of calcium tungstate (scheelite [CaWO4]) and zirconium oxide
      (baddeleyite [ZrO2]), which were chemical components of the sealer cement.

PMID- 18037066
TI  - Menetrier's disease coexisting with ulcerative colitis and sclerosing
      cholangitis.

PMID- 18037067
TI  - Early prediction of anastomotic leakage after colorectal surgery by measuring
      peritoneal cytokines: prospective study.
AB  - BACKGROUND: Anastomotic leakage (AL) is a major cause of postoperative mortality
      and morbidity in colorectal surgery. We investigated the early prediction of
      peritoneal cytokine levels in developing AL after colorectal surgery. METHODS:
      Thirty-four patients with colorectal carcinoma, who underwent elective surgery,
      were included prospectively. Peritoneal samples were collected on the fifth
      postoperative day and interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha
      were measured. Patients were divided into two groups: those with clinical
      evidence of AL (group 1) and those without any evidence of AL (group 2). RESULTS:
      Of the 34 patients undergoing anastomoses, clinically evident AL occurred in 4
      patients (11.7%). There was a positive correlation between AL and peritoneal
      cytokine levels and blood loss and operation time and hospital stay. Peritoneal
      cytokine levels were significantly higher in group 1 as compared to group 2. The
      significant increase in patients with AL was observed between peritoneal cytokine
      levels and the postoperative days. However, a significant decrease in patients
      without AL was observed. CONCLUSION: The peritoneal cytokine levels can be an
      additional diagnostic tool that can support the early prediction of AL in
      colorectal surgery.

PMID- 18037068
TI  - Australians' health at crossroads.

PMID- 18037069
TI  - What next for the UK's research assessment exercise?

PMID- 18037070
TI  - Calling for research into deafness.

PMID- 18037071
TI  - Rotavirus vaccines must perform in low-income countries too.

PMID- 18037072
TI  - Is venous thrombosis a risk factor for arterial thrombosis?

PMID- 18037073
TI  - Can antidepressants prevent psychosis?

PMID- 18037076
TI  - Foresight report on obesity.

PMID- 18037078
TI  - Foresight report on obesity.

PMID- 18037079
TI  - UN Declaration on the Rights of Indigenous Peoples.

PMID- 18037080
TI  - Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the
      first 2 years of life in European infants: randomised, double-blind controlled
      study.
AB  - BACKGROUND: We aimed to assess the efficacy of the oral live attenuated human
      rotavirus vaccine Rotarix (RIX4414) for prevention of rotavirus gastroenteritis
      in European infants during their first 2 years of life. METHODS: 3994 study
      participants were enrolled from six countries and were randomly assigned two oral
      doses of either RIX4414 (n=2646) or placebo (n=1348), which were coadministered
      with the first two doses of specific childhood vaccinations. Follow-up for
      gastroenteritis episodes was undertaken from 2 weeks post-dose two through the
      two consecutive rotavirus seasons following vaccinations (combined efficacy
      follow-up period; mean duration 17 months [SD 1.6]). Our primary endpoint was
      vaccine efficacy against rotavirus gastroenteritis of any severity during the
      first efficacy follow-up period (2 weeks post-dose two to the end of the first
      rotavirus season). Stool specimens obtained during gastroenteritis episodes were
      tested for rotavirus by ELISA and typed by RT-PCR. Episodes scoring 11 or greater
      on the 20-point Vesikari scale were classified as severe. Analysis was according
      to protocol. This study is registered with ClinicalTrials.gov, number NCT00140686
      (eTrack102247). FINDINGS: 120 infants were excluded from the according-to
      protocol analysis. During the first efficacy follow-up period (mean duration 5.7
      months [SD 1.2]), 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given
      placebo had rotavirus gastroenteritis episodes of any severity, resulting in a
      vaccine efficacy of 87.1% (95% CI 79.6-92.1; p<0.0001). For the combined efficacy
      follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was
      90.4% (85.1-94.1; p<0.0001), for admission owing to rotavirus gastroenteritis
      96.0% (83.8-99.5; p<0.0001), and for rotavirus-related medical attention 83.8%
      (76.8-88.9; p<0.0001), and significant protection against severe rotavirus
      gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown.
      INTERPRETATION: In a European setting, two doses of RIX4414 coadministered with
      childhood vaccines provided high protection against any and severe rotavirus
      gastroenteritis, with an overall reduction of admissions for gastroenteritis over
      two consecutive rotavirus epidemic seasons.

PMID- 18037081
TI  - Venous thromboembolism and subsequent hospitalisation due to acute arterial
      cardiovascular events: a 20-year cohort study.
AB  - BACKGROUND: In some studies, venous thromboembolism has been associated with
      atherosclerosis and with the risk of arterial cardiovascular events such as
      myocardial infarction and stroke. Other studies, however, do not show this
      association. To help clarify these discrepant findings, we aimed to investigate
      the risk of arterial cardiovascular events in patients who were diagnosed with
      venous thromboembolism. METHODS: We undertook a 20-year population-based cohort
      study using data from nationwide Danish medical databases. After excluding those
      with known cardiovascular disease, we assessed the risk of myocardial infarction
      and stroke in 25,199 patients with deep venous thrombosis, 16,925 patients with
      pulmonary embolism, and 163,566 population controls. FINDINGS: For patients with
      deep venous thrombosis, the relative risks varied from 1.60 for myocardial
      infarction (95% CI 1.35-1.91) to 2.19 (1.85-2.60) for stroke in the first year
      after the thrombotic event. For patients with pulmonary embolism, the relative
      risks in that year were 2.60 (2.14-3.14) for myocardial infarction and 2.93 (2.34
      3.66) for stroke. The relative risks were also raised, though less markedly,
      during the subsequent 20 years of follow-up, with 20-40% increases in risk for
      arterial cardiovascular events. Relative risks were similar for those with
      provoked and unprovoked deep venous thrombosis and pulmonary embolism.
      INTERPRETATION: Patients with venous thromboembolism have a substantially
      increased long-term risk of subsequent arterial cardiovascular events.

PMID- 18037082
TI  - Gastrobronchial fistula.

PMID- 18037083
TI  - Where is the primary tumour?

PMID- 18037084
TI  - Prenatally diagnosed urinary tract abnormalities: long-term outcome.
AB  - The long-term outcomes of prenatally detected uropathies are poorly documented.
      Limited data on fetal intervention show a possible reduction in early mortality
      from pulmonary hypoplasia, but no beneficial effect on long-term prognosis for
      renal function. Prenatally detected vesicoureteric reflux (VUR) is characterised
      by males with high-grade primary reflux, who are at long-term risk of renal
      impairment. Prenatal diagnosis and surgical intervention have contributed to a
      reduction in long-term morbidity in children with pelviureteric junction (PUJ)
      obstruction. By the same token, many children have almost certainly undergone
      unnecessary early pyeloplasty for an obstruction that would have resolved
      spontaneously. Multicystic dysplastic kidney (MCDK) carries a low (1%) risk of
      hypertension in childhood. The limited evidence on the long-term outcome of mild
      dilatation (pelvicaliectasis) indicates this is a largely innocent finding, which
      carries no increased risk of morbidity.

PMID- 18037085
TI  - Use of ultrasonic dissection in the early surgical management of periorbital
      haemangiomas.
AB  - PURPOSE: To evaluate the efficacy and safety of the early surgical excision of
      periorbital haemangiomas with an ultrasonic scalpel in infants at risk of visual
      impairment. STUDY: A retrospective analysis of 67 infants diagnosed to be at risk
      of amblyopia from periorbital haemangiomas, treated consecutively with the
      Dissectron between 1994 and 2005. Ophthalmic outcome parameters included the pre-
      and postoperative measurement of visual axis occlusion, strabismus, astigmatism,
      and degree of amblyopia. RESULTS: Visual performance showed an overall
      improvement of 30% following treatment. Seventy-six patients were found to have
      abnormal ophthalmic examinations preoperatively, compared to 46 following
      surgery. After surgery, visual axis occlusion decreased from 73 to 6%; amblyopia
      decreased from 67 to 22%, strabismus decreased from 26 to 18% and astigmatism
      (>onedioptre) decreased from 66 to 31%. Mean astigmatism values decreased from
      3.5 to 1.9 dioptres. No new cases of astigmatism, strabismus or amblyopia were
      diagnosed postoperatively. Three minor complications resolved with conservative
      treatment. All patients were satisfied with the outcome of their surgery.
      CONCLUSION: Early surgical excision of periorbital haemangiomas using the
      Dissectron in infants with an established risk of visual impairment is a safe and
      effective alternative to pharmacological therapy. The use of the Dissectron is
      associated with reduced operative times and a shorter hospital stay.

PMID- 18037087
TI  - Mapping techniques for atrial fibrillation ablation.
AB  - Atrial fibrillation (AF) is a common arrhythmia. Although significant work still
      needs to be done, recent advances in understanding the mechanism of AF have led
      to the development of elegant catheter mapping techniques for ablation of AF.
      These improved mapping techniques are complemented by an evolution in various
      imaging and navigational technologies, several of which can now be combined in a
      process called registration, so that the physician no longer needs to rely solely
      on a mental image of the anatomy of the left atrium and the pulmonary vein while
      attempting to ablate the region. Ongoing advances in mapping technique will
      increase safety and efficacy and it is likely that AF ablation will become the
      first-line therapy in most patients with this complicated arrhythmia.

PMID- 18037088
TI  - Quiz page December 2007: diarrhea and anuria in a recipient of an en bloc infant
      kidney transplant.

PMID- 18037089
TI  - Should reducing nocturnal blood pressure be a therapeutic target in CKD? The time
      is ripe for a clinical outcomes trial.

PMID- 18037090
TI  - Tolvaptan, an oral vasopressin V2 receptor antagonist for heart failure?

PMID- 18037091
TI  - Changing the timing of antihypertensive therapy to reduce nocturnal blood
      pressure in CKD: an 8-week uncontrolled trial.
AB  - BACKGROUND: Nondipping status is associated with greater cardiovascular morbidity
      and mortality and faster progression of chronic kidney disease (CKD). We examined
      whether shifting 1 antihypertensive drug from morning to evening restores the
      circadian rhythm of blood pressure in nondipper patients with CKD. STUDY DESIGN:
      8-week clinical trial without a control group. SETTING & PARTICIPANTS: We
      selected from our outpatient renal clinic 32 patients with CKD with estimated
      glomerular filtration rate less than 90 mL/min/1.73 m(2) and night-day ratio of
      mean ambulatory blood pressure (ABP) greater than 0.9, but with normal daytime
      ABP (<135/85 mm Hg) to avoid the required therapy intensification. INTERVENTION:
      Shifting 1 antihypertensive drug from morning to evening. OUTCOMES: Percentage of
      patients changing the night-day ratio of mean ABP from greater than 0.9 to 0.9 or
      less 8 weeks after the shift. MEASUREMENTS: Office blood pressure/ABP and
      proteinuria at baseline and after the shift. RESULTS: There were 55% men with a
      mean age of 67.4 +/- 11.3 years and estimated glomerular filtration rate of 46 +/
      12 mL/min/1.73 m(2). They were treated with 2.4 +/- 1.4 antihypertensive drugs.
      After the drug shift, the night-day ratio of mean ABP decreased in 93.7% of
      patients, with normal circadian rhythm restored in 87.5%. The nocturnal systolic
      and diastolic ABP decrease was not associated with an increase in diurnal ABP and
      was independent from number and class of shifted drug. Office blood pressure in
      the morning also decreased (from 136 +/- 16/77 +/- 10 to 131 +/- 13/75 +/- 8 mm
      Hg; P = 0.02). Urinary protein excretion decreased from 235 +/- 259 to 167 +/-
      206 mg/d (P < 0.001). LIMITATIONS: Absence of a control group and patients with
      severe proteinuria or uncontrolled daytime ABP. CONCLUSIONS: In nondipper
      patients with CKD, changing the timing of antihypertensive therapy decreases
      nocturnal blood pressure and proteinuria.

PMID- 18037092
TI  - Calibration of serum creatinine in the National Health and Nutrition Examination
      Surveys (NHANES) 1988-1994, 1999-2004.
AB  - BACKGROUND: The calibration of serum creatinine values to standardized creatinine
      and the commutability of serum creatinine across surveys are essential to the
      correct use of National Health and Nutrition Examination Survey (NHANES) data for
      kidney function and for generating estimates of the burden of kidney disease in
      the United States. STUDY DESIGN: Calibration study of serum creatinine in NHANES
      III (1988-1994) and NHANES 1999-2000, 2001-2002, and 2003-2004 to directly
      compare creatinine measurements from the original surveys with standard
      creatinine measured using an assay traceable to known gold-standard methods. We
      also assessed predictors of differences between methods (potential interferences)
      in this general population. SETTING & PARTICIPANTS: The NHANES are ongoing cross
      sectional surveys of the civilian noninstitutionalized population of the United
      States. We selected random samples of approximately 200 stored specimens from
      persons aged 60 years or older from each survey (NHANES III, 1999-2000, 2001
      2002, and 2003-2004). MEASUREMENTS: Stored serum specimens from the 4 NHANES
      surveys were analyzed for serum creatinine by using a Roche enzymatic assay
      implemented at the Cleveland Clinic Research Laboratory (CCRL). The Roche assay
      is traceable to gold-standard reference methods. The original NHANES serum
      creatinine values were obtained using the Jaffe method (kinetic alkaline picrate)
      implemented in several different laboratories. RESULTS: Overall agreement between
      the original NHANES values (Jaffe method) and CCRL measurements (Roche enzymatic)
      was high, but substantial biases were observed in NHANES III and 1999-2000. No
      bias was observed in NHANES 2001-2002 and 2003-2004. Final calibration equations
      to correct serum creatinine values in the relevant surveys are provided. Assay
      differences were independent of sex, race/ethnicity, and bilirubin and
      triglyceride levels, but weakly related to age and glucose concentration.
      LIMITATIONS: We were not able to examine drift in measurements over time within
      each survey or directly evaluate freeze-thaw effects. CONCLUSIONS: The magnitude
      of differences in serum creatinine measurements in NHANES III and 1999-2000 from
      standard creatinine would result in large differences in estimates of kidney
      function (10% to 20%). Thus, correction of original creatinine values in NHANES
      III and 1999-2000 is essential, but no correction is needed for NHANES 2001-2002
      or 2003-2004.

PMID- 18037093
TI  - Modification of the Modification of Diet in Renal Disease (MDRD) Study equation
      for Japan.
AB  - BACKGROUND: Glomerular filtration rate (GFR)-estimating equations based on serum
      creatinine level may not be accurate across racial groups because of differences
      among races in creatinine generation. The Modification of Diet in Renal Disease
      (MDRD) Study equation was developed in whites and African Americans, but
      performance was not evaluated in Japanese. STUDY DESIGN: Diagnostic test
      accuracy. Cross-sectional retrospective study of 3 patient groups. Equation
      development in 2 groups (n = 247 in 2002 to 2004; n = 214 in 2003 to 2004 with
      measured GFR <90 mL/min/1.73 m(2)); external validation in a separate group (n =
      153 from 1988 to 1994). SETTING & PARTICIPANTS: Hospitalized Japanese patients
      with chronic kidney disease in 3 medical centers. REFERENCE TEST: Measured GFR
      (mGFR) computed from renal clearance of inulin. INDEX TEST: Estimated GFR (eGFR)
      using the isotope dilution mass spectrometry (IDMS)-traceable 4-variable MDRD
      Study equation, a modified IDMS MDRD Study equation with a Japanese Society of
      Nephrology-Chronic Kidney Disease Initiatives (JSN-CKDI) coefficient derived in
      the development data set, and a new equation derived by refitting coefficients in
      the MDRD Study equation in the development data set. MEASUREMENTS: Current
      creatinine assays were calibrated to standardized creatinine. Performance of
      equations was assessed as bias, accuracy, root-mean-squared error, and
      correlation coefficient of eGFR versus mGFR. RESULTS: In the development data
      set, eGFR using the IDMS MDRD Study equation overestimated mGFR throughout the
      entire range. In the validation data set, the IDMS MDRD Study equation with the
      JSN-CKDI coefficient 0.741 and the new equation (JSN-CKDI) performed with
      significantly less bias and greater accuracy than the IDMS MDRD Study equation,
      but were similar to each other in accuracy and bias in patients with eGFR less
      than 60 mL/min/1.73 m(2). In the combined development and validation data sets,
      the JSN-CKDI coefficient was 0.763 (95% confidence interval, 0.743 to 0.783).
      LIMITATIONS: Possible drift in creatinine assays over time, possible lower
      creatinine generation in hospitalized patients, exclusion of patients with higher
      GFR from the development data set. CONCLUSION: GFR estimates using the IDMS MDRD
      Study equation with the JSN-CKDI coefficient or the new JSN-CKDI equation are
      more accurate than the IDMS MDRD Study equation in hospitalized Japanese patients
      with eGFR less than 60 mL/min/1.73 m(2). More studies are necessary to verify the
      accuracy of the JSN-CKDI coefficient and JSN-CKDI equation in other settings in
      Japan and elsewhere in Asia.

PMID- 18037094
TI  - The effect of age, sex, and race on urinary markers of kidney damage in children.
AB  - BACKGROUND: The aim of this study is to examine the effects of age, sex, and race
      on the excretion and concentrations of albumin, gamma-glutamyl transpeptidase
      (gamma-GT), N-acetyl-beta-d-glucosaminidase (NAG), alpha(1)-microglobulin
      (alpha1M), and creatinine in children. STUDY DESIGN: Secondary analysis of a
      clinical trial, The New England Children's Amalgam Trial, which examined effects
      of amalgam dental fillings. SETTING & PARTICIPANTS: 534 children aged 6 to 10
      years at baseline were recruited from Boston, MA, and rural Maine. PREDICTORS:
      Age, sex, and race. OUTCOMES & MEASUREMENTS: Urine samples were collected
      annually for 5 years and analyzed for creatinine, albumin, gamma-GT, NAG, and
      alpha1M concentrations. Repeated-measures analysis of covariance was used to
      model effects of age, sex, and race on these values, as well as calculated
      excretion rates. RESULTS: All measures of creatinine and gamma-GT increased
      significantly with age. Albumin and gamma-GT concentration and excretion
      (milligrams per gram of creatinine or units per gram creatinine) were
      significantly greater for girls compared with boys. alpha1M concentration and
      creatinine excretion were greater for boys compared with girls. Creatinine
      concentration was significantly greater for blacks than for whites and Hispanics.
      Creatinine excretion and all gamma-GT levels were significantly greater for
      blacks and Hispanics compared with non-Hispanic whites. LIMITATIONS: The study
      population, recruited for a clinical trial, was of lower socioeconomic status
      than the general population. The high limit of detection for alpha1M resulted in
      a majority of samples less than the detection limit. CONCLUSIONS: We recommend
      considering age, sex, and race in the interpretation of urinary markers. It also
      is recommended that epidemiological studies and clinical trials account for age,
      sex, and race in statistical models comparing urinary markers of kidney damage.

PMID- 18037095
TI  - A randomized trial of a 6-week course of celecoxib on proteinuria in diabetic
      kidney disease.
AB  - BACKGROUND: Preclinical data suggest that cyclooxygenase 2 inhibitors decrease
      proteinuria and preserve glomerular structure in animal models of diabetic
      nephropathy. The objective of this study is to compare the efficacy and safety of
      celecoxib with placebo for decreasing proteinuria in patients with diabetic
      nephropathy. STUDY DESIGN: Placebo-controlled double-blinded crossover design.
      SETTING & PARTICIPANTS: 24 patients with type 1 or 2 diabetes mellitus,
      proteinuria with protein of 500 mg/d or greater, and serum creatinine level of
      3.0 mg/dL or less. INTERVENTION: Patients were randomly assigned to: (1) 6 weeks
      of celecoxib followed by a 3-week washout period, followed by 6 weeks of placebo
      followed by another 3-week washout; or (2) 6 weeks of placebo followed by a 3
      week washout, followed by 6 weeks of celecoxib followed by another 3-week washout
      period. All patients were administered quinapril, 20 to 40 mg/d, or irbesartan,
      150 to 300 mg/d. All patients were administered aspirin, 81 mg/d. OUTCOMES &
      MEASUREMENTS: Proteinuria was assessed by means of protein-creatinine ratio. Data
      were analyzed using the mixed-effect statistical model. RESULTS: There was no
      significant difference in urinary proteinuria after 6 weeks of treatment with
      placebo or celecoxib (proteinuria ratio, celecoxib versus placebo, 1.041; 95%
      confidence interval, 0.846 to 1.282). Celecoxib had no significant effect on
      potassium or estimated glomerular filtration rate. Frequencies of adverse events
      were similar between the placebo and celecoxib treatments. LIMITATIONS: This
      pilot study was not designed to evaluate the safety or long-term clinical effects
      of celecoxib. CONCLUSIONS: Celecoxib, 200 mg/d, for 6 weeks did not alter
      proteinuria. Few adverse events were noted in this high-risk population.

PMID- 18037096
TI  - Hypernatremia in the critically ill is an independent risk factor for mortality.
AB  - BACKGROUND: Hypernatremia is common in the intensive care unit (ICU). We assessed
      the prevalence of hypernatremia and its impact on mortality and ICU length of
      stay (LOS). STUDY DESIGN: Retrospective analysis. SETTING & PARTICIPANTS: All
      patients admitted to a medical ICU of a university hospital during a 35-month
      observation period. PREDICTOR: Hypernatremia (serum sodium > 149 mmol/L) after
      admission to the ICU. OUTCOMES & MEASUREMENTS: Main outcomes were 28-day hospital
      mortality and ICU LOS. Demographic factors, main diagnosis, and severity of
      illness. Cox proportional hazards regression models were used for data analysis.
      RESULTS: Of 981 patients, 90 (9%) had hypernatremia, on admission to the ICU in
      21 (2%) and developed during the ICU stay in 69 patients (7%). Of these 981
      patients, 235 (24%) died; LOS was 8 +/- 9 (SD) days. Mortality rates were 39% and
      43% in patients with hypernatremia on admission or that developed after admission
      compared with 24% in patients without hypernatremia (P < 0.01). LOS was 20 +/- 16
      days in patients with hypernatremia compared with 8 +/- 10 days in patients
      without hypernatremia (P < 0.001). In multivariable analysis, hypernatremia was
      an independent risk factor for mortality (relative risk, 2.1; 95% confidence
      interval, 1.4 to 3.3). LIMITATIONS: Retrospective design, absence of data for
      long-term mortality. CONCLUSIONS: Most cases of hypernatremia in the ICU
      developed after admission, suggesting an iatrogenic component in its evolution.
      Hypernatremia is associated with increased mortality. Strategies for preventing
      hypernatremia in the ICU should be encouraged.

PMID- 18037097
TI  - Children on long-term dialysis in the United States: findings from the 2005 ESRD
      clinical performance measures project.
AB  - BACKGROUND: The Centers for Medicare & Medicaid Services End-Stage Renal Disease
      Clinical Performance Measures (CPM) Project contains one of the largest databases
      of prevalent pediatric dialysis patients in the United States. Since 2005, the
      CPM Project has included not only children on long-term hemodialysis (HD)
      therapy, but also those on long-term peritoneal dialysis (PD) therapy. This study
      describes demographic and clinical characteristics and compares them between
      patients on HD and PD therapy. STUDY DESIGN: Cross-sectional. SETTING &
      PARTICIPANTS: Children aged 0 to younger than 18 years included within the 2005
      End-Stage Renal Disease CPM Project. PREDICTOR: Demographic and clinical
      characteristics, with emphasis on dialysis modality. OUTCOMES & MEASUREMENTS:
      Achievement of values for hemoglobin, dialysis adequacy, and serum albumin as
      recommended by recent National Kidney Foundation-Kidney Disease Outcomes Quality
      Initiative Clinical Practice Guidelines and Recommendations. RESULTS: Of 1,453
      patients examined, 692 received HD and 761 received PD. There was no significant
      difference by dialysis modality in the likelihood of having a mean hemoglobin
      level of 11 g/dL or greater; however, HD patients were significantly more likely
      to have a mean hemoglobin level less than 10 g/dL (19% versus 14% of PD patients;
      P = 0.02). Although statistically significant, the absolute difference in mean
      hemoglobin levels between patients receiving HD versus PD was small (11.4 versus
      11.6 g/dL). Eighty-nine percent of patients receiving HD and 87% of patients
      receiving PD achieved the recommended modality-specific Kt/V (P = 0.4). Children
      receiving HD were more likely than those receiving PD to have a mean serum
      albumin level of 4.0/3.7 g/dL or greater (bromcresol green/bromcresol purple
      laboratory method): 46% versus 33% (P < 0.001). LIMITATIONS: Because of study
      design, only associations can be described. CONCLUSIONS: A significant number of
      children had hemoglobin, serum albumin, and/or Kt/V values outside the
      recommended targets. Future research is needed to better define the risk
      relationships of these predictors with morbidity and mortality in children on
      dialysis therapy, evaluate the benefit of treating to certain treatment targets,
      and understand reasons for failing to reach treatment targets in individual
      patients or patient groups.

PMID- 18037098
TI  - Treatment of peritoneal dialysis-associated peritonitis: a systematic review of
      randomized controlled trials.
AB  - BACKGROUND: Peritonitis frequently complicates peritoneal dialysis. Appropriate
      treatment is essential to reduce adverse outcomes. Available trial evidence about
      peritoneal dialysis peritonitis treatment was evaluated. SELECTION CRITERIA FOR
      STUDIES: The Cochrane CENTRAL Registry (2005 issue), MEDLINE (1966 to February
      2006), EMBASE (1985 to February 2006), and reference lists were searched to
      identify randomized trials of treatments for patients with peritoneal dialysis
      peritonitis. INTERVENTIONS: Trials of antibiotics (comparisons of routes, agents,
      and dosing regimens), fibrinolytic agents, peritoneal lavage, and intraperitoneal
      immunoglobulin. OUTCOMES: Treatment failure, relapse, catheter removal,
      microbiological eradication, hospitalization, all-cause mortality, and adverse
      reactions. RESULTS: 36 eligible trials were identified: 30 trials (1,800
      patients) of antibiotics; 4 trials (229 patients) of urokinase; 1 trial of
      peritoneal lavage (36 patients); and 1 trial of intraperitoneal immunoglobulin
      (24 patients). No superior antimicrobial class was identified. In particular,
      glycopeptides and first-generation cephalosporins were equivalent (3 trials, 387
      patients; relative risk [RR], 1.84; 95% confidence interval [CI], 0.95 to 3.58).
      Simultaneous catheter removal/replacement was superior to urokinase at decreasing
      treatment failures (1 trial, 37 patients; RR, 2.35; 95% CI, 1.13 to 4.91).
      Continuous and intermittent intraperitoneal antibiotic dosing were equivalent
      regarding treatment failure (4 trials, 338 patients; RR, 0.69; 95% CI, 0.37 to
      1.30) and relapse (4 trials, 324 patients; RR, 0.93; 95% CI, 0.63 to 1.39). One
      trial showed superiority of intraperitoneal antibiotics over intravenous therapy.
      LIMITATIONS: The method quality of trials generally was suboptimal and outcome
      definitions were inconsistent. Small patient numbers led to inadequate power to
      show an effect. Interventions, such as optimal duration of antibiotic therapy,
      were not evaluated. CONCLUSIONS: Trials did not identify superior antibiotic
      regimens. Intermittent and continuous antibiotic dosing are equivalent treatment
      strategies.

PMID- 18037099
TI  - Efficacy of intravenous methoxy polyethylene glycol-epoetin beta administered
      every 2 weeks compared with epoetin administered 3 times weekly in patients
      treated by hemodialysis or peritoneal dialysis: a randomized trial.
AB  - BACKGROUND: C.E.R.A. (methoxy polyethylene glycol-epoetin beta), a continuous
      erythropoietin receptor activator, was developed to provide stable control of
      hemoglobin (Hb) levels at extended administration intervals in patients with
      chronic kidney disease. We examined its efficacy for Hb level correction when
      administered once every 2 weeks in erythropoiesis-stimulating agent-naive
      dialysis patients. STUDY DESIGN: Open-label, multicenter, randomized, parallel
      group, phase 3 study. SETTING & PARTICIPANTS: Dialysis patients (age >or= 18
      years). INTERVENTION: Patients (n = 181) were randomly assigned (3:1) to receive
      intravenous C.E.R.A. once every 2 weeks or epoetin 3 times weekly. OUTCOMES &
      MEASUREMENTS: The primary end point was Hb level response rate (increase in Hb
      level >or= 1 g/dL [10 g/L] versus baseline and Hb level >or= 11 g/dL [110 g/L]
      without blood transfusion during the 24-week correction period) in the intent-to
      treat population. RESULTS: Hb response rates (intent-to-treat population) were
      93.3% with C.E.R.A. and 91.3% with epoetin. Similar results were found in the per
      protocol population. Peak mean Hb levels were 12.28 +/- 1.13 (SD) g/dL (122.8 +/-
      11.3 g/L) with C.E.R.A. and 12.19 +/- 1.24 g/dL (121.9 +/- 12.4 g/L) with
      epoetin. Mean change in Hb levels from baseline to the end of the correction
      period were 2.70 +/- 1.45 g/dL (27 +/- 14.5 g/L) with C.E.R.A. and 2.56 +/- 1.31
      g/dL (25.6 +/- 13.1 g/L) with epoetin. Both treatments were generally well
      tolerated. LIMITATIONS: Open-label study design, 3:1 randomization, limited
      peritoneal dialysis population, descriptive statistics, and lack of formal
      prespecified comparison to epoetin. CONCLUSIONS: Intravenous C.E.R.A. once every
      2 weeks may be as safe and effective as 3-times-weekly epoetin for correcting
      anemia in dialysis patients. These results show the utility of intravenous
      C.E.R.A. administered once every 2 weeks in erythropoiesis-stimulating agent
      naive dialysis patients.

PMID- 18037100
TI  - Neuropeptide Y and markers of osteoblast activity in dialysis patients: a cross
      sectional study.
AB  - BACKGROUND: In mice, neuropeptide Y (NPY) decreases bone turnover by means of a
      parathyroid hormone-independent effect on osteoblast activity. STUDY DESIGN:
      Cross-sectional study. SETTING & PARTICIPANTS: We studied the relationship
      between levels of NPY and biomarkers of osteoblast activity in 161 nondiabetic
      patients with end-stage renal disease (131 patients, hemodialysis; 30 patients,
      continuous ambulatory peritoneal dialysis). PREDICTORS & OUTCOMES: We performed
      an analysis of demographic and clinical variables associated with NPY as a
      dependent variable and a second analysis testing the association of NPY (as an
      independent variable) with markers of osteoblast activity. RESULTS: Peritoneal
      dialysis as treatment modality (beta = 0.37; P < 0.001) and longer duration of
      dialysis therapy (beta = 0.24; P < 0.01) were independently related to plasma
      NPY. NPY level was related inversely (P < 0.001) to serum alkaline phosphatase
      and bone alkaline phosphatase levels (P = 0.01). The NPY-alkaline phosphatase
      link was confirmed in a multiple regression analysis adjusting for a series of
      potential confounders, including parathyroid hormone. In a categorical analysis
      in which the study population was divided according to NPY quartiles, the
      proportion of patients with low alkaline phosphatase levels was lowest in the
      first 2 NPY quartiles (26%) and highest in NPY quartile 4 (80%; P < 0.001), and
      this association held true in a multiple logistic regression analysis, indicating
      that the risk of low alkaline phosphatase level increases in parallel with NPY
      level. LIMITATIONS: The hypothesis generated by this cross-sectional study needs
      to be confirmed in cohort studies. CONCLUSIONS: The inverse relationships between
      levels of NPY and biomarkers of bone turnover support the hypothesis that NPY may
      be implicated in low bone turnover in dialysis patients by a central parathyroid
      independent mechanism.

PMID- 18037101
TI  - Relationships of N-terminal pro-B-natriuretic peptide and cardiac troponin T to
      left ventricular mass and function and mortality in asymptomatic hemodialysis
      patients.
AB  - BACKGROUND: Although the cardiac biomarker troponin T (cTnT) is related strongly
      to mortality in patients with end-stage renal disease, the independent
      association of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and cTnT
      levels in predicting outcomes is unknown. The objective of this study is to
      determine factors associated with NT-pro-BNP and cTnT and determine whether these
      levels are associated with mortality. STUDY DESIGN: Cohort study. SETTING &
      PARTICIPANTS: Asymptomatic hemodialysis patients (n = 150) in 4 university
      affiliated hemodialysis units. EXPOSURE & OUTCOMES: For cross-sectional analysis,
      echocardiographic variables as exposures and NT-pro-BNP and cTnT levels as
      outcomes; for longitudinal analysis, association of NT-pro-BNP and cTnT levels as
      exposures to all-cause and cardiovascular disease mortality as outcomes. RESULTS:
      In a multivariate regression analysis, low midwall fractional shortening, a
      measure of poor systolic function, was an independent correlate of log NT-pro-BNP
      level (P < 0.01), whereas left ventricular mass index was an independent
      correlate of cTnT level (P < 0.01). During a median follow-up of 24 months, 46
      patients died, 26 of cardiovascular causes. NT-pro-BNP levels had a strong graded
      relationship with all-cause (hazard ratios [HRs], 1.54, 4.78, and 4.03 for
      increasing quartiles; P < 0.001) and cardiovascular mortality (HRs, 2.99, 10.95,
      and 8.54; P < 0.01), whereas cTnT level had a weaker relationship with all-cause
      (HRs, 1.57, 2.32, and 3.39; P < 0.01) and cardiovascular mortality (HRs, 0.81,
      2.12, and 2.14; P = 0.1). The combination of the 2 biomarker levels did not
      improve the association with all-cause or cardiovascular mortality compared with
      NT-pro-BNP level alone. NT-pro-BNP level was a marker of mortality even after
      adjusting for left ventricular mass index and midwall fractional shortening.
      LIMITATIONS: Our cohort was predominantly black and of limited sample size.
      CONCLUSION: NT-pro-BNP level strongly correlates with left ventricular systolic
      dysfunction and is associated more strongly with mortality than cTnT level in
      asymptomatic hemodialysis patients.

PMID- 18037102
TI  - Fenestration of the Gerota's fascia as symptomatic treatment of floating kidneys.
AB  - A 16-year-old man presented with severe nephrotic syndrome complicated by massive
      perirenal fluid. Percutaneous drainage of fluid was performed 3 times, followed
      by improvement in renal function and hypertension, but perirenal fluid recurred
      within days. Nephrotic syndrome was unresponsive to steroid therapy. A
      laparoscopic bilateral fenestration of Gerota's fascia and peritoneum allowed
      permanent drainage of fluid into the peritoneal cavity. During the same
      procedure, a renal wedge biopsy was performed. Histological examination showed
      advanced focal glomerular sclerosis of the tip lesion variant. The glomerular
      disease was refractory to further treatment with cyclophosphamide, mycophenolate,
      and rituximab. However, perirenal fluid did not recur despite persistent
      nephrotic syndrome, showing that fenestration of Gerota's fascia is a successful
      treatment of floating kidneys in such patients.

PMID- 18037103
TI  - Massively enlarged polycystic kidneys in monozygotic twins with TCF2/HNF-1beta
      (hepatocyte nuclear factor-1beta) heterozygous whole-gene deletion.
AB  - TCF2, the gene encoding for hepatocyte nuclear factor 1beta, is involved in early
      renal development. Mutations in TCF2 lead to heterogeneous renal phenotypes.
      Antenatal ultrasonography may show unilateral/bilateral hyperechogenic or
      enlarged cystic kidneys. In children or adults, cystic renal hypoplasia/dysplasia
      is a common feature, occasionally associated with maturity-onset diabetes of the
      young type 5 and genital tract abnormalities. We report an unusual presentation
      characterized by massively enlarged polycystic kidneys mimicking autosomal
      dominant polycystic kidney disease in monozygotic twins. Bilateral enlarged
      cystic kidneys were discovered in week 13 of a gemellic pregnancy. Postnatally,
      kidney size increased in both children, reaching 16 cm at 20 years. Nephromegaly
      was associated with bilateral cysts and a slowly decreasing glomerular filtration
      rate (40 mL/min/1.73 m(2) at 20 years). There was neither pancreatic nor genital
      malformation. Non-type 1 diabetes mellitus was diagnosed incidentally in both
      twins at 20 years. Knowledge of early-onset diabetes (at age 19 years) in their
      father prompted us to search for the TCF2 mutation. Genetic analysis showed
      complete TCF2 heterozygous whole-gene deletion in both twins. Genetic testing
      could not be performed in the father. Bilateral massively enlarged polycystic
      kidneys mimicking autosomal dominant polycystic kidney disease in young adults
      may be related to TCF2 mutation. Although uncommon, this new phenotype enlarges
      the clinical spectrum of kidney involvement associated with TCF2 mutation. In
      this case, maturity-onset diabetes of the young-type diabetes paved the way to
      accurate diagnosis.

PMID- 18037104
TI  - Treatment of idiopathic membranous nephropathy with the herb Astragalus
      membranaceus.
AB  - A 77-year-old woman with nephrotic syndrome secondary to idiopathic membranous
      nephropathy was treated with angiotensin-converting enzyme inhibitors,
      angiotensin receptor blockers, cyclosporine A, and mycophenolate mofetil, without
      response. After more than 2 years of unremitting nephrosis, she began therapy
      with the herb Astragalus membranaceus, used by traditional Chinese physicians to
      treat various immune disorders, including glomerulonephritis. After institution
      of Astragalus at a dose of 15 g/d, there was a marked decrease in proteinuria.
      Nephrotic syndrome recurred after temporary cessation of Astragalus therapy, with
      complete remission of nephrosis observed after its reintroduction. The clinical
      course of this patient suggests that Astragalus may have beneficial effects in
      patients with idiopathic membranous nephropathy.

PMID- 18037105
TI  - Elevated fibroblast growth factor 23 in a patient with metastatic prostate cancer
      and hypophosphatemia.

PMID- 18037106
TI  - Two brothers in one Chinese family with collagen type III glomerulopathy.

PMID- 18037107
TI  - Evaluation of the potential living kidney donor.

PMID- 18037108
TI  - Managing dialysis catheter-related Staphylococcus aureus bacteremia.

PMID- 18037110
TI  - Nephrocalcinosis in phosphate nephropathy following oral phosphate purgative: a
      role for underlying subclinical primary hyperparathyroidism?

PMID- 18037113
TI  - Vasculitis: a collection of pearls and myths.
AB  - Since Kussmaul and Maier described the index case of vasculitis in 1866, the
      field has seen many changes. What was considered for decades to be only a single
      disorder is now known to consist of at least 15 to 20 distinct conditions.
      Important strides have been made in unraveling the pathophysiology of some
      individual forms of vasculitis, but many mysteries remain. Over time, numerous
      myths and occasional pearls have arisen from the care of patients with these
      disorders. This collection of pearls and myths gathers lessons about the status
      of clinical care of vasculitis patients in the year 2008.

PMID- 18037114
TI  - Targeting B lymphocytes as therapy for ANCA-associated vasculitis.
AB  - This article focuses on the initial results achieved with the more selective
      immunosuppressive approach of B-lymphocyte depletion in patients who fail
      cyclophosphamide or have contraindications for its use in the treatment of
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This
      novel approach has sparked hope for patients and physicians in their search for
      effective, well-tolerated therapy for AAV. B-cell depletion is now undergoing
      rigorous investigation in randomized clinical trials.

PMID- 18037115
TI  - Airway involvement in Wegener's granulomatosis.
AB  - Wegener's granulomatosis is characterized by necrotizing granulomatous
      inflammation and necrotizing vasculitis affecting predominantly small arteries,
      arterioles, capillaries, and venules. In contrast to the well-described pulmonary
      parenchymal involvement of Wegener's granulomatosis, the lower airway
      (tracheobronchial) disease manifestations are less well recognized by clinicians.
      Consequently, mild disease of the airways is easily missed. There is a relative
      paucity of published information on various tracheobronchial manifestations of
      Wegener's granulomatosis. This article provides a comprehensive review of the
      diagnosis and management of the infraglottic tracheobronchial disease
      manifestations.

PMID- 18037116
TI  - Takayasu arteritis: what is the long-term prognosis?
AB  - Takayasu arteritis (TA) is a form of idiopathic large vessel vasculitis that
      predominantly affects women of reproductive age. Although TA is a rare disease,
      the interpretation of longitudinal data from several countries provides new
      insights into the clinical course and outcomes in TA across different racial and
      ethnic groups. Contemporary studies belie prior perceptions of TA as a disease
      with a self-limited, benign course. We now recognize this disease as one that
      often relapses, leaves the patient chronically dependent on glucocorticoids for
      disease control, and frequently leads to disability. Limited data suggest that
      the targeted inhibition of tumor necrosis factor (TNF) might be an effective
      therapy for TA.

PMID- 18037117
TI  - Pyoderma gangrenosum: an update.
AB  - Pyoderma gangrenosum (PG) can be differentiated into classic and atypical forms.
      The classic form is characterized by ulcers and the atypical form by deep
      erosions with bullous blue-gray margins. Pathergy, the development of cutaneous
      lesions at sites of trauma, is a common feature of both forms of PG.
      Approximately 50% of patients who have PG have underlying systemic diseases, most
      commonly inflammatory bowel disease, myeloproliferative disorders, and various
      forms of inflammatory arthritis. The diagnosis of PG is one of exclusion. The
      management of this disorder begins with treatment of any underlying disease and
      local or systemic glucocorticoids or immunomodulating therapies.

PMID- 18037118
TI  - Retroperitoneal fibrosis: evolving concepts.
AB  - Retroperitoneal fibrosis (RPF) is a rare fibro-inflammatory condition that is
      idiopathic in most cases, but may be secondary to various causes. Although the
      cause and pathogenesis of the idiopathic form are unknown, immunogenetic factors
      and immunopathologic/autoimmune mechanisms are probably involved. Idiopathic RPF
      usually develops around the abdominal aorta and iliac arteries but in some cases
      may also involve the thoracic aorta and the origin of its major branches, with a
      pattern similar to that of other forms of large-vessel vasculitis. In addition,
      the disease is frequently associated with autoimmune conditions affecting other
      organs. Glucocorticoids alone or in combination with immunosuppressive agents are
      usually effective treatment options, but the disease frequently has a chronic
      relapsing course.

PMID- 18037119
TI  - Five clinical conundrums in the management of giant cell arteritis.
AB  - Clinicians who treat patients with giant cell arteritis (GCA) face many
      unresolved challenges. Visual loss still occurs in 15% to 20% of patients despite
      the availability of therapy for the disease that is generally effective. Aneurysm
      formation and large vessel stenosis are increasingly recognized complications.
      Substantial iatrogenic morbidity stems from glucocorticoid therapy, and recent
      trials have failed to identify an efficient steroid sparing agent. In this
      review, the authors address five major clinical conundrums in the management of
      GCA.

PMID- 18037120
TI  - Scleritis and peripheral ulcerative keratitis.
AB  - Scleritis and peripheral ulcerative keratitis (PUK) can present as isolated
      conditions or as part of a systemic inflammatory or infectious disorder. Both are
      serious ocular conditions that can result in vision loss and require early
      diagnosis and treatment. Nearly two thirds of patients with non-infectious
      scleritis require systemic glucocorticoid therapy and one fourth need a
      glucocorticoid-sparing agent as well. Essentially all patients with non
      infectious PUK require systemic glucocorticoids. A detailed clinical history,
      thorough physical examination, and thoughtful laboratory evaluations are
      important in the exclusion of underlying disorders and extraocular involvement.

PMID- 18037121
TI  - Cogan's syndrome: an audiovestibular, ocular, and systemic autoimmune disease.
AB  - Cogan's syndrome is an immune-mediated systemic disorder characterized by ocular
      and audiovestibular inflammation. Although interstitial keratitis in the absence
      of an infectious cause is the classic form of eye involvement, other nonspecific
      inflammatory eye diseases can also occur, often making prompt diagnosis of the
      underlying disease challenging. The audiovestibular disease is difficult to treat
      and can lead to profound hearing loss. A poor outcome, especially complete
      hearing loss, can sometimes be prevented through a timely recognition and
      initiation of glucocorticoid therapy at the onset of the disease.

PMID- 18037122
TI  - Insights into amyloid-beta-induced mitochondrial dysfunction in Alzheimer
      disease.
AB  - Amyloid-beta has long been implicated in the pathogenesis of Alzheimer disease.
      The focus was initially on the extracellular fibrillar deposits of amyloid-beta
      but more recently has shifted to intracellular oligomeric forms of amyloid-beta.
      Unfortunately, the mechanism(s) by which either extracellular or intracellular
      amyloid-beta induces neuronal toxicity remains unclear. That said, a number of
      recent studies indicate that mitochondria might be an important target of amyloid
      beta. Neurons rely heavily on mitochondria for energy and it is well established
      that mitochondrial dysfunction might be an important target of amyloid-beta.
      Mechanistically, amyloid-beta aggregates in mitochondria to impair function,
      leading to energy hypometabolism and elevated reactive oxygen species production.
      Additionally, amyloid-beta affects the balance of mitochondrial fission/fusion
      and mitochondrial transport, negatively impacting a host of cellular functions of
      neurons. Here, we review the role that amyloid-beta plays in mitochondrial
      structure and function of neurons and the importance of this in the pathogenesis
      of Alzheimer disease.

PMID- 18037123
TI  - Ifosfamide induces acute renal failure via inhibition of the thioredoxin
      reductase activity.
AB  - The present study investigated the impact of ifosfamide (IFO) on renal
      thioredoxin reductase (TrxR) activity. In mice treated with IFO for 6 h, TrxR
      activity significantly decreased in a dose-dependent manner. Subsequently, acute
      renal failure (ARF) occurred dose-dependently. Like IFO, the well-established
      TrxR-specific inhibitor auranofin suppresfssed renal TrxR activity and generated
      ARF too. TrxR was inactivated by IFO preferentially over other antioxidant
      parameters at 6 h; however, it recovered nearly to normal levels within 12 h.
      When auranofin was administered at 6 h after IFO treatment, the recovery at 12 h
      was sharply attenuated. Consequently, ARF was pronouncedly exacerbated. IFO
      within its maximum tolerated dose did not considerably deplete renal glutathione.
      However, escalating IFO dose strikingly attacked both the thioredoxin and the
      glutathione systems, resulting in lethality, which implies that glutathione
      depletion sensitizes IFO-induced nephrotoxicity and cosuppression of both systems
      causes more severe toxicological consequences than suppressing the thioredoxin
      system alone. Indeed, combining IFO with buthionine sulfoximine, an inhibitor of
      glutathione synthesis, induced much more severe ARF than IFO alone did. Taken
      together, inhibition of renal TrxR activity can be considered as a pivotal
      mechanism of IFO-induced ARF, and individuals with lower levels of renal
      glutathione are at high risk of incurring ARF after IFO treatment.

PMID- 18037124
TI  - Oxidation and structural perturbation of redox-sensitive enzymes in injured
      skeletal muscle.
AB  - Molecular events that control skeletal muscle injury and regeneration are poorly
      understood. However, inflammation associated with oxidative stress is considered
      a key player in modulating this process. To understand the consequences of
      oxidative stress associated with muscle injury, inflammation, and regeneration,
      hind-limb muscles of C57Bl/6J mice were studied after injection of cardiotoxin
      (CT). Within 1 day post-CT injection, polymorphonuclear neutrophilic leukocyte
      accumulation was extensive. Compared to baseline, tissue myeloperoxidase (MPO)
      activity was elevated eight- and fivefold at 1 and 7 days post-CT, respectively.
      Ubiquitinylated protein was elevated 1 day postinjury and returned to baseline by
      21 days. Cysteine residues of creatine kinase (CK) and glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) were irreversibly oxidized within 1 day post-CT injection
      and were associated with protein conformational changes that fully recovered
      after 21 days. Importantly, protein structural alterations occurred in
      conjunction with significant decreases in CK activity at 1, 3, and 7 days post-CT
      injury. Interestingly, elevations in tissue MPO activity paralleled the time
      course of conformational changes in CK and GAPDH. In combination, these results
      demonstrate that muscle proteins in vivo are structurally and functionally
      altered via the generation of reactive oxygen species produced during
      inflammatory events after muscle injury and preceding muscle regeneration.

PMID- 18037125
TI  - Anti-inflammatory effects of 8-hydroxy-2'-deoxyguanosine on lipopolysaccharide
      induced inflammation via Rac suppression in Balb/c mice.
AB  - Recently, we observed that 8-hydroxyguanosine triphosphate and 8-hydroxy-2'
      deoxyguanosine (oh(8)dG) inactivate Rac and consequently down-regulate the Rac
      linked NADPH oxidase, iNOS, and Cox2. Based on these observations, we tested
      whether oh(8)dG has anti-inflammatory activity in vivo in lipopolysaccharide
      (LPS)-treated mice. LPS (1 mg/kg, ip)-treated mice exhibit marked inflammatory
      responses, including increases in proinflammatory cytokines (TNF-alpha, IL-6, IL
      18, and IL-12p70) in serum and infiltration of neutrophils, increased
      translocation of NF-kappaB p50 from the cytosol to the nucleus, and
      phosphorylation of c-Jun in lung tissues. Mice were pretreated with oh(8)dG (up
      to 60 mg/kg, ip) 4 h before LPS injection, and this pretreatment dose-dependently
      inhibited the inflammatory responses; the inhibitions observed with 60 mg/kg
      oh(8)dG were statistically significant. At the same time, oh(8)dG pretreatment
      inactivated Rac in lung tissues. Oh(8)dG pretreatment (50 mg/kg, ip) also
      significantly protected against LPS-induced septic death. Furthermore, oh(8)dG
      was more effective than acetyl salicylic acid in inhibiting these inflammatory
      responses. 8-Hydroxyguanosine also had some effect but was much weaker than
      oh(8)dG. The effects of normal nucleosides (dG, G, and A) were negligible or not
      significant. These results support an anti-inflammatory activity for oh(8)dG,
      which could be ascribed to its Rac-inactivating action.

PMID- 18037126
TI  - 4-Hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase is degraded
      by cathepsin G.
AB  - Degradation of oxidized or oxidatively modified proteins is an essential part of
      the antioxidant defenses of cells. 4-Hydroxy-2-nonenal (HNE), a major reactive
      aldehyde formed by lipid peroxidation, causes many types of cellular damage. It
      has been reported that HNE-modified proteins are degraded by the ubiquitin
      proteasome pathway or, in some cases, by the lysosomal pathway. However, our
      previous studies using U937 cells showed that HNE-modified glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) is degraded by an enzyme that is sensitive to a
      serine protease inhibitor, diisopropyl fluorophosphate (DFP), but not a
      proteasome inhibitor, MG-132, and that its degradation is not catalyzed in the
      acidic pH range where lysosomal enzymes are active. In the present study, we
      purified an HNE-modified GAPDH-degrading enzyme from a U937 cell extract to a
      final active fraction containing two proteins of 28 kDa (P28) and 27 kDa (P27)
      that became labeled with [(3)H]DFP. Using peptide mass fingerprinting and a
      specific antibody, P28 and P27 were both identified as cathepsin G. The
      degradation activity was inhibited by cathepsin G inhibitors. Furthermore, a cell
      extract from U937 cells transfected with a cathepsin G-specific siRNA hardly
      degraded HNE-modified GAPDH. These results suggest that cathepsin G plays a role
      in the degradation of HNE-modified GAPDH.

PMID- 18037127
TI  - Sequence-specific oxidative base modifications in hypoxia-inducible genes.
AB  - Reactive oxygen species associated with hypoxic signaling in pulmonary arterial
      endothelial cells (PAECs) oxidatively modify specific nucleotides in the hypoxic
      response element (HRE) of the VEGF gene (FASEB J.19:387-394; 2005). In this
      study, we determined in PAECs if hypoxia caused genome-wide oxidative
      modifications or if they were restricted to the promoters of genes differentially
      regulated by hypoxia. Comet assays indicated that there were no differences
      between normoxic and hypoxic PAECs in terms of global DNA damage. However, a
      simple PCR-based method involving DNA amplification before and after treatment
      with formamidopyrimidine DNA glycosylase (Fpg), a bacterial DNA repair enzyme
      that cleaves at sites of purine base oxidation, revealed that hypoxia caused
      modifications in the HREs of the hypoxia-inducible VEGF, HO-1, and ET-1 genes
      which coincided with accumulation of their respective mRNA transcripts. Promoter
      sequences not involved with hypoxic induction and coding regions of these genes
      failed to display Fpg-sensitive sites. Oxidative modifications also were not
      detected in sequences of the hypoxia down-regulated ornithine decarboxylase and
      TFAM genes or the constitutively expressed beta-actin gene. These findings show
      that hypoxia-mediated oxidative DNA modifications cluster in functionally
      relevant promoter sequences in hypoxia-inducible genes and suggest that such
      oxidative modifications may be biologically significant.

PMID- 18037128
TI  - Evidence for cancer-associated expression of NADPH oxidase 1 (Nox1)-based oxidase
      system in the human stomach.
AB  - Helicobacter pylori infection has been suggested to stimulate expression of the
      NADPH oxidase 1 (Nox1)-based oxidase system in guinea pig gastric epithelium,
      whereas Nox1 mRNA expression has not yet been documented in the human stomach.
      PCR of human stomach cDNA libraries showed that Nox1 and Nox organizer 1 (NOXO1)
      messages were absent from normal stomachs, while they were specifically
      coexpressed in intestinal- and diffuse-type adenocarcinomas including signet-ring
      cell carcinoma. Immunohistochemistry showed that Nox1 and NOXO1 proteins were
      absent from chronic atrophic gastritis (15 cases), adenomas (4 cases), or
      surrounding tissues of adenocarcinomas (45 cases). In contrast, Nox1 and its
      partner proteins were expressed in intestinal-type adenocarcinomas (19/21 cases),
      diffuse-type adenocarcinomas (15/15 cases), and signet-ring cell carcinomas (9/9
      cases). Confocal microscopy revealed that Nox1, NOXO1, Nox activator 1, and
      p22(phox) were predominantly associated with Golgi apparatus in these cancer
      cells, while diffuse-type adenocarcinomas also contained cancer cells having Nox1
      and its partner proteins in their nuclei. Nox1-expressing cancer cells exhibited
      both gastric and intestinal phenotypes, as assessed by expression of mucin core
      polypeptides. Thus, the Nox1-base oxidase may be a potential marker of neoplastic
      transformation and play an important role in oxygen radical- and inflammation
      dependent carcinogenesis in the human stomach.

PMID- 18037130
TI  - Elevated F2-isoprostanes in thalassemic patients.
AB  - This study was aimed at investigating oxidative stress in thalassemic patients by
      measurement of the oxidative damage biomarker, F(2)-isoprostanes (F(2)-IsoPs),
      using gas chromatography-mass spectrometry. The results showed that the mean
      value of urinary F(2)-IsoPs, normalized with creatinine, in the thalassemic group
      was significantly higher than that from healthy subjects (3.38+/-2.15 ng/mg
      creatinine vs 0.86+/-0.55 ng/mg creatinine, respectively), and the mean value of
      plasma total F(2)-IsoPs in the thalassemic group was also significantly higher
      than that from healthy subjects (0.39+/-0.15 ng/ml vs 0.18+/-0.03 ng/ml,
      respectively). Serum ferritin, erythrocyte superoxide dismutase (SOD),
      glutathione peroxidase, glutathione, and TBARS levels after treatment of
      erythrocytes with H(2)O(2) were also investigated, and serum ferritin and
      erythrocyte SOD levels were significantly higher in thalassemic patients. Our
      findings are consistent with oxidative stress in thalassemia patients.

PMID- 18037129
TI  - Low nitric oxide: a key factor underlying copper-deficiency teratogenicity.
AB  - Copper (Cu)-deficiency-induced teratogenicity is characterized by major cardiac,
      brain, and vascular anomalies; however, the underlying mechanisms are poorly
      understood. Cu deficiency decreases superoxide dismutase activity and increases
      superoxide anions, which can interact with nitric oxide (NO), reducing the NO
      pool size. Given the role of NO as a developmental signaling molecule, we tested
      the hypothesis that low NO levels, secondary to Cu deficiency, represent a
      developmental challenge. Gestation day 8.5 embryos from Cu-adequate (Cu+) or Cu
      deficient (Cu-) dams were cultured for 48 h in Cu+ or Cu- medium, respectively.
      We report that NO levels were low in conditioned medium from Cu-/Cu- embryos and
      yolk sacs, compared to Cu+/Cu+ controls under basal conditions and with NO
      synthase (NOS) agonists. The low NO production was associated with low
      endothelial NOS phosphorylation at serine 1177 and cyclic guanosine-3',5'
      monophosphate (cGMP) concentrations in the Cu-/Cu- group. The altered NO levels
      in Cu-deficient embryos are functionally significant, as the administration of
      the NO donor DETA/NONOate increased cGMP and ameliorated embryo and yolk sac
      abnormalities. These data support the concept that Cu deficiency limits NO
      availability and alters NO-dependent signaling, which contributes to abnormal
      embryo and yolk sac development.

PMID- 18037131
TI  - Age-dependent upregulation of p53 and cytochrome c release and susceptibility to
      apoptosis in skeletal muscle fiber of aged rats: role of carnitine and lipoic
      acid.
AB  - Mitochondrial dysfunction has been implicated in the regulation of myofiber loss
      during aging, possibly by apoptotic pathways. However, the mitochondrial-mediated
      pathway of apoptosis by cytochrome c in skeletal muscle remains ambiguous. To
      understand this, we have studied the upstream and downstream events of cytochrome
      c release, and assessed the efficacy of carnitine and lipoic acid
      cosupplementation. The results show that elevated levels of cytosolic cytochrome
      c activate apoptosis in aged rats, and was confirmed further by in vitro caspase
      3 assay. Interestingly, the exogenous addition of cytochrome c results in a much
      higher increase of caspase-3 activity in aged treated rats than age-matched
      control rats, strongly suggesting that cytochrome c is a limiting factor for
      caspase-3 activation in the cytosol. Carnitine and lipoic acid supplement
      decreased apoptosis in aged rats by maintaining mitochondrial membrane integrity
      and thereby preventing further loss of cytochrome c in vivo. Furthermore, the
      upregulation of p53 observed in aged rats is attributed to the loss of outer
      mitochondrial membrane integrity and subsequent release of cytochrome c through
      BH3-only proteins. In conclusion, the p53-dependent activation of the
      mitochondrial-cytochrome c pathway of apoptosis in the present study suggests the
      existence of cross talk between mitochondria and nucleus. However, the exact
      molecular mechanism remains to be explored. Oral supplements of carnitine and
      lipoic acid play an antiapoptotic role in aged rat skeletal muscle by protecting
      mitochondrial membrane integrity.

PMID- 18037132
TI  - The JNK pathway and neuronal migration.
AB  - The c-Jun N-terminal kinases (JNKs) are important regulators of a variety of
      physiological and pathological processes both in the central and in the
      peripheral nervous systems. JNKs are considered as crucial mediators of neuronal
      cell death in response to stress and injury. However, recent studies have
      provided substantial evidence that the JNK pathway plays an important role in
      neuronal migration. Here, we will give a brief introduction of the JNK signaling
      pathway and put more emphasis on its role in neuronal migration.

PMID- 18037133
TI  - Identification of differentially expressed microRNAs during the development of
      Chinese murine mammary gland.
AB  - MicroRNAs (miRNAs) are endogenous approximately 22 nucleotide-long noncoding
      RNAs. In this study, to investigate miRNA expression profiles and their functions
      in mammary gland development, we have used microarray as well as qRT-PCR, to
      analyze the miRNA expression changes along the murine mammary cycle during
      pregnancy, particularly on transition from pregnancy to lactation. It shows that
      every developmental stage of the mammary gland has its own miRNA expression
      pattern. Compared with virgin and involution, some miRNAs such as miR-138 and miR
      431 are downregulated, whereas, some miRNAs such as miR-133 and miR-133a-133b are
      upregulated during pregnancy and lactation. These results indicate that miRNAs
      are functionally involved in mammary gland development.

PMID- 18037134
TI  - Effect of menopause on gene expression profiles of circulating monocytes: a pilot
      in vivo microarray study.
AB  - Menopause is one of the key physiological events in the female life and can
      increase the risk for a number of complex autoimmune, neurodegenerative,
      metabolic, and cardiovascular disorders. Circulating monocytes can differentiate
      into various cell types and play an important role in tissue morphogenesis and
      immune response. We studied gene expression profiles of peripheral blood
      monocytes in healthy pre- and postmenopausal women using Affymetrix Human U133A
      GeneChip array that contains probes for approximately 14,500 genes. Comparative
      analyses between the samples showed that 20 genes were up- and 20 were down
      regulated. Of these genes, 28 were classified into six major GO categories
      relevant to such biological processes as the cell proliferation, immune response,
      cellular metabolism, and the others. The remaining 12 genes have yet unidentified
      biological functions. Our results support the hypothesis that functional state of
      circulating monocytes is indeed affected by menopause, and resulting changes may
      be determined through the genomewide gene expression profiling. Several
      differentially expressed genes identified in this study may be candidates for
      further studies of menopause-associated systemic autoimmune, neurodegenerative,
      and cardiovascular disorders. Our study is only the first attempt in this
      direction, but it lays a basis for further research.

PMID- 18037135
TI  - Microsatellite DNA marker analysis of genetic diversity in wild common carp
      (Cyprinus carpio L.) populations.
AB  - Thirty microsatellite loci were used for analyzing six wild populations of common
      carp (Cyprinus carpio L.). Observed (H(o)) and expected (H(e)) heterozygosity
      values, polymorphic information content (PIC), and number of effective alleles
      (A(e)) were all detected. Genetic similarity index and genetic distance were
      computed based on the allele frequency. The Hardy-Weinberg Equilibrium was
      checked according to the test of chi2. Genetic differentiation and hierarchical
      partition of genetic diversity were evaluated by F(ST) and N(m). A clustering
      dendrogram was made based on the results of UPGMA methods using the PHYLIP
      software package (version 3.63). There were totally 8,136 fragments ranging from
      125 bp to 414 bp in length. Three to thirteen alleles were amplified in 30 loci
      and 210 alleles in all six populations. The average number of alleles in each
      locus was seven. The result showed that 1) the level of genetic variability was
      moderate in the six populations. Polymorphic information contents of the six wild
      common carp populations were 0.44, 0.52, 0.53, 0.57, 0.63, and 0.64 respectively.
      Effective alleles were from 1.04 to 4.72, the average numbers in each population
      were 2.19, 2.60, 2.42, 2.43, 2.45, and 2.33. The average expected heterozygosity
      values were 0.50, 0.59, 0.56, 0.56, 0.57, and 0.54 respectively; 2) the highest
      genetic similarity index that came from the populations of BR and ZL was 0.8511
      and the lowest index was 0.6688, and it came from the populations of BR and HN.
      There was a correlation between the clustering result and the geographical
      distribution.

PMID- 18037137
TI  - Analysis on genetic diversity and isolation mechanism by distance of different
      ecological type sheep breeds in Mongolia sheep group.
AB  - In the present study with Tan sheep, small-tailed Han sheep, Hu sheep, Tong
      sheep, and Wadi sheep, we detected the distribution of gene frequency of several
      microsatellite sites in different chromosomes, the result showed that: 1) Hu
      sheep was in the status of Hardy-Weinberg extreme disequilibrium (P < 0.01),
      while populations including Tong sheep, small-tailed Han sheep, Tan sheep, and
      Wadi sheep were in Hardy-Weinberg equilibrium (P > 0.05). 2) Variance analysis of
      the heterozygosity and polymorphic information content at microsatellite makers
      showed that there were not significant differences among populations as to
      heterozygosity and PIC (P > 0.05), as to effective number of alleles there were
      not significant differences both among Tan sheep, Hu sheep, Tong sheep, and Wadi
      sheep, and between Wadi sheep and small-tailed sheep (P > 0.05), but between the
      former three populations and the latter two populations, there were significant
      differences (0.01<P < 0.05). The variation levels of small-tailed Han sheep was
      the highest in the five populations based on microsatellite maker data,
      subsequently followed by Wadi sheep, Tong sheep, Tan sheep, and then Hu sheep. 3)
      The phylogenetic relationships of the five sheep populations in this study did
      not meet the mechanism of isolation by distance, and the genetic differentiation
      relationships among five sheep populations were not closely linearly correlative
      with their geography distribution. Our findings supported related records in
      literature:The five populations originated on different time stage from the
      primogenitor population and communicated genetically with each other thereafter
      in the process of natural and artificial selection and on different ecological
      environment.

PMID- 18037136
TI  - In silico cloning, expression and phylogenetic analysis of pig GATA-3 gene.
AB  - Pig GATA-3 cDNA was obtained by reverse transcription polymerase chain reaction
      (RT-PCR), using in silico cloning strategy based on pig dbEST. The length of pig
      GATA-3 cDNA is 1,760 bp containing a 1,335 bp open reading frame (ORF), which
      encodes a 444 amino acid protein. Semi-quantitative RT-PCR analysis of GATA-3
      mRNA expression was done using the total RNAs from different normal tissues of a
      large white pig. The GATA-binding family of transcription factors comprised of a
      subgroup of DNA-binding proteins that both bound the consensus GATA motif and
      contained the class IV zinc finger motif. The molecular evolution tree was
      constructed based on the GATA-3 amino acid sequence and class IV zinc finger
      motif using mega 3.1. Phylogeny analysis of GATA factors isolated from
      vertebrates suggested that the six distinct vertebrate GATAs had descended from a
      common ancestral sequence, and the topology also suggested multiple modes of
      evolution including gene duplication and class IV zinc finger motif
      recombination. These data helped the authors in illuminating the pathways of
      divergent and convergent evolution of the GATA-binding family of transcription
      factors.

PMID- 18037138
TI  - Genetic analysis of six endangered local duck populations in China based on
      microsatellite markers.
AB  - Seventeen microsatellite loci were used to assess the genetic variation and
      population structure of six endangered duck populations in China. PIC,
      heterozygosity with two estimators of genetic differentiation (F(ST) and G(ST)),
      and Nei's standard genetic distance were evaluated. The results showed that these
      six endangered duck populations showed high polymorphism. The proportion of inter
      population subdivision among the six duck populations ranged between 17.0 and
      14.7%. The average heterozygosity was 0.706, 0.702, 0.691, 0.676, 0.604, and
      0.660 in the Gaoyou, Liancheng, Jinding, Beijing, Shaoxing, and Jianchang ducks,
      respectively. The average PIC ranged from 0.561 to 0.663. Finally, the results
      showed higher genetic diversity and difference above the levels of genetic
      variation among all the populations.

PMID- 18037139
TI  - Fine mapping and isolation of Bc7(t), allelic to OsCesA4.
AB  - Several brittle culm mutants of rice were identified and characterized. In this
      study, we characterized a brittle mutant (bc7(t)) identified from japonica
      variety Zhonghua 11 by means of 60Co-gamma radiation. This mutant displays normal
      phenotype similar to its wild type plants except for the fragility of all plant
      body, with approximately 10% decrease in the cellulose content. The genetic
      analysis and gene fine mapping showed that the bc7(t) mutant was controlled by a
      recessive gene, residing on an 8.4 kb region of the long arm of chromosome 1. The
      gene annotation indicated that there was only one putative gene encoding
      cellulose synthase catalytic subunit (CesA) in this region, which was allelic to
      OsCesA4. Furthermore, the sequence analysis was carried out and 7 bases deletion
      in the junction of exon 10 and intron 10 was done in bc7(t) mutant, resulting in
      the change of reading frame and the consequent failure to generate functional
      protein. In addition, the result of RNA interference experiment showed that when
      the Bc7(t) was knocked down, the transplants exhibited fragility, similar to
      bc7(t) mutant. The finding of novel allele of OsCesA4 locus will facilitate the
      understanding of the mechanism of cell wall biosynthesis. The potential
      utilization of the bc7(t) mutant in animal food was discussed as well.

PMID- 18037140
TI  - Studies on the inheritance of locule formation in tomatoes (Lycopersicon
      esculentum Mill.).
AB  - To fully understand the tomato ovary locule formation of inheritance, two
      varieties, ovary multi-locule (MLK1) and few-locule (FL1), were used in these
      studies. Using reciprocal cross, self-cross, and backcross, we have constructed
      various groups to seek the genetic law and mechanisms of tomato locule formation,
      for modifying the tomato breeding theory. The parental and the resulting F1 and
      F2 generations have been used to examine the heredity of the locule number. The
      results showed that few-locule was incompletely dominant. The data from backcross
      demonstrated a significant effect on the locule number, whereas, the reciprocal
      cross showed an insignificant effect. Not surprisingly, the locule number was
      controlled by nuclear genomes, not by exogenous substances. The model that
      inherited the locule number belonged to the additive-dominant model: additive
      effects played a very important role and were partially dominant. In addition,
      the results revealed that the locule number in tomato was mainly controlled by a
      single gene, whereas, it was modulated by a number of other genes. Finally, the
      general inheritability and narrow inheritability of the locule number were 69.44%
      and 52.98%, respectively.

PMID- 18037141
TI  - Population genetic structure in apricot (Prunus armeniaca L.) cultivars revealed
      by fluorescent-AFLP markers in southern Xinjiang, China.
AB  - Population-wide genetic structure was studied using fluorescent-AFLP markers on
      85 apricot (Prunus armeniaca L.) cultivars collected from Kuche, Kashi, Hetian in
      the Tarim Basin, southern Xinjiang Uygur Autonomous Region of China. The purpose
      of this study was to determine the genetic structure and genotypic diversity
      among the different eco-geographical populations. Based on the results from this
      study, 8 pairs of fluorescent-AFLP primers showed clear electrophoregram and high
      polymorphism amongst the 64 pairs of EcoR|/Mse|(Mse|--a FAM fluorescent marked
      primer) primers screened. There was a significant polymorphic difference for the
      same primer pair in different populations and for the same population with
      different primer pairs. The percentage of polymorphic loci (P) at species level
      was higher than Kuche, Hetian, Kashi population levels, respectively. The Nei's
      gene diversity index (H) and Shannon's information index (I) at species level
      were higher than those of Kuche, Hetian, and Kashi at population level,
      respectively. H and I of Kuche population were the highest amongst the three
      populations. Apricot population genetic diversity was found mainly within the
      population. Genetic differentiation coefficient between populations (G(ST)) was
      0.0882. Gene flow Nm between the populations was 5.1689. Population genetic
      identity was between 0.9772-0.9811 and genetic distance was between 0.0191
      0.0232. These results further indicated that the similarity between populations
      was higher and the genetic distance between populations was smaller. The UPGMA
      cluster analysis indicates that the geographical populations at Kuche, Kashi,
      Hetian were relatively independent Mendelian populations. Concurrently, there was
      also partial gene exchange between the populations. All the evidences indicated
      that the genetic diversity in Kuche population was the highest, suggesting that
      it could be a transition population from wild apricot to cultivated apricot.
      There were abundant genetic diversities in apricot cultivar populations in
      southern Xinjiang, China, which provide promising germplasm for further breeding
      and theoretical basis for biodiversity conservation and utilization for apricot
      population in this area.

PMID- 18037143
TI  - Word processing in Parkinson's disease is impaired for action verbs but not for
      concrete nouns.
AB  - Recent studies have demonstrated that processing of action words recruits
      cortical motor regions that are also involved in the planning and execution of
      the actions words refer to. The functional role of these regions in word
      understanding remains, however, to be clarified. The present study investigates
      this issue by examining the impact of Parkinson's disease (PD) on lexical
      decision performance for action words, relative to concrete nouns, in a masked
      priming paradigm. Priming effects for the two word categories were measured in
      non-demented PD patients off and on dopaminergic treatment, and in healthy
      participants. Our results revealed that although overall performances did not
      differ between verbs and nouns, priming effects showed a clear dissociation
      between word categories. While priming for concrete nouns was not affected by
      Levodopa intake, it dissociated as a function of treatment for action verbs. No
      priming was actually obtained for action verbs in PD patients off dopaminergic
      treatment. Following Levodopa intake, this deficit recovered, however, because
      priming effects for verbs became comparable to those for concrete nouns and
      similar to performance of healthy participants. Overall, this study thus brings
      compelling evidence that processing lexico-semantic information about action
      words depends on the integrity of the motor system.

PMID- 18037142
TI  - Elimination of rat spinal substance P receptor bearing neurons dissociates
      cardiovascular and nocifensive responses to nicotinic agonists.
AB  - Intrathecal (IT) delivery of nicotinic agonists evokes dose dependent nocifensive
      behavior and cardiovascular responses. Previous studies suggested that these
      effects may be attenuated by the loss of substance P positive (sP(+)) primary
      afferents. To further characterize these cell systems, we examined the effect of
      selectively destroying neurokinin 1 receptor bearing (NK1-r(+)) dorsal horn
      neurons on IT nicotinic agonist evoked responses. In the dorsal spinal cord,
      confocal immunohistochemical microscopy revealed that nAChR subunits (alpha3,
      alpha4, alpha5, beta2 and beta4), NeuN B (neuronal marker) and NK1-r were all co
      expressed in the superficial dorsal horn; however alpha3, alpha5, beta2 and beta4
      exhibited the highest degree of colocalization with NK1-r expressing neurons.
      After intrathecal substance P-saporin (sP-SAP), NK1-r(+) cell bodies and
      dendrites in the superficial dorsal horn were largely abolished. The greatest
      loss in co-expression of nAChR subunits with NK1-r was observed with alpha3,
      alpha5, beta2 and beta4 subunits. Following intrathecal sP-SAP, the nocifensive
      responses to all nicotinic agonists were reduced; however, in contrast, while
      cardiovascular responses evoked by IT nicotine were unaltered, IT cytisine and
      epibatidine exhibited enhanced tachycardia and pressor responses. These results
      indicate subunit-specific relationships between the NK1-r and nicotinic receptor
      systems. The loss of nocifensive activity after destruction of the NK1-r bearing
      cells in spite of the persistence of nicotinic subunits on other cells,
      emphasizes the importance of the superficial marginal neuron in mediating these
      nicotinic effects. Further, the exaggerated cardiovascular responses to cytisine
      following loss of NK1-r bearing cells suggest the presence of a nicotinic
      receptor-mediated stimulation of inhibitory circuits at the spinal level.

PMID- 18037144
TI  - Characterisation of secreted polysaccharides and (glyco)proteins from suspension
      cultures of Pyrus communis.
AB  - High molecular weight material recovered from the culture filtrate of cell
      suspension cultured Pyrus communis was composed of 81% carbohydrate, 13% protein
      and 5% inorganic material. This material was separated into three fractions (one
      neutral (Fraction A) and two acidic (Fractions B and C)), by anion-exchange
      chromatography on DEAE-Sepharose CL-6B using a gradient of imidazole-HCl at pH
      7.0. The monosaccharide and linkage composition of each fraction was determined
      after carboxyl reduction of uronic acid residues. From the combined results of
      the carbohydrate analyses, we conclude that the high molecular weight
      extracellular material consists of three major and two minor polysaccharides: a
      (fucogalacto)xyloglucan (36%) in the unbound neutral Fraction A; a type II
      arabinogalactan (as an arabinogalactan-protein, 29%) and an acidic
      (glucurono)arabinoxylan (2%) in Fraction B; and a galacturonan (33%) and a trace
      of heteromannan in Fraction C. The main amino acids in the proteins were Glx,
      Thr, Ser, Hyp/Pro and Gly. Further separation of Fraction B by solvent partition,
      SDS-PAGE and analysis by LC-MS/MS identified the major proteins as two
      chitanases, two thaumatin-like proteins, a beta-1,3-glucanase, an extracellular
      dermal glycoprotein and a pathogenesis-related protein.

PMID- 18037145
TI  - Vegetable tannins - lessons of a phytochemical lifetime.
AB  - After the early encouragement from the outstanding contribution in the early
      1900s of Emil Fischer to an understanding of vegetable tannins the work of the
      following half-century had simply exemplified the complexity of the problems they
      presented. It was generally recognised [Freudenberg, 1920. Die Chemie der
      Naturliche Gerbstoffe. Springer, Berlin] that there was a broad division into
      condensed or non-hydrolysable and hydrolysable tannins but much else remained
      vague and untidy. In the 1950s Bate-Smith and Swain gave the lead into totally
      new ways of looking at these substances. They drew aside for the first time the
      curtains on the botanical aspects of these substances to reveal the rich vistas
      which lay beyond. It was to initiate remarkable progress in the next fifty years
      in the understanding of their chemistry and biochemistry; some of the principal
      developments of this work are reviewed herein.

PMID- 18037146
TI  - [Cheek defect reconstruction with a vertical translation flap: nine cases].
AB  - INTRODUCTION: Cheeks are frequently the sites of common skin tumors. Surgery is
      the common treatment of those lesions and the operative defect can be important.
      The aim of this study was to present reconstruction of lateromedial cheek defects
      with a vertical translation flap. PATIENTS AND METHODS: Nine patients (three
      women and six men) with a mean age of 46 years (21-74) were included. The defect
      was located in the medial part of the cheek in all cases with a mean diameter of
      5 cm (4-6). The incision was made between the cheek, lateral nasal area, upper
      and lower lips, and chin aesthetic units. Then the flap was vertically translated
      and the upper end was fixed to the adjacent periosteum. The average follow-up was
      four years. RESULTS: In all cases the defect was covered and there was no case
      flap necrosis. In one case a postoperative paresia of the marginal ramus was
      noted and two patients presented with minor ectropion without lagopthalmia.
      DISCUSSION: In our experience this type of flap is indicated in large cheek
      defects without extension to nasal ala, upper lip, and lower eyelid.

PMID- 18037147
TI  - [A long-lasting sinusitis].

PMID- 18037148
TI  - The structure of the female sand fly (Phlebotomus papatasi) alimentary canal.
AB  - In the sand fly vector, Leishmania parasites are confined to the alimentary
      canal. During much of their development, promastigotes are attached to the wall
      of the gut via their flagella. In this context, the surface of the different
      regions of the sand fly alimentary tract lumen warrants scientific attention. In
      this paper, the various regions are described, for the first time using scanning
      electron microscopy. The cibarium and the pharynx, which function as pumping
      organs, are lined with cuticle. Parts of the cibarium and the pharynx bear
      different types of cuticular spines and appendages. The midgut is lined with
      microvillar epithelium, which secretes the peritrophic matrix following a blood
      meal. The wider proximal part of the hindgut (= pylorus) is lined with transverse
      cuticular ridges with tentacle-like appendages. Leishmania major promastigotes
      were found to anchor themselves in the midgut and the stomodaeal valve via their
      flagella. The possible roles of the different internal structures and their
      importance for the development of Leishmania parasites are discussed.

PMID- 18037149
TI  - Identification of Leishmania donovani as a cause of cutaneous leishmaniasis in
      Sudan.
AB  - Eight patients with cutaneous ulcers were referred to the Institute of Endemic
      Diseases, Khartoum, Sudan, from June 2000 to March 2002 for the diagnosis of
      suspected cutaneous leishmaniasis (CL). Diagnosis was confirmed parasitologically
      by both positive Giemsa-stained smears and successful culture of Leishmania
      promastigotes in NNN medium. The eight parasite isolates were shown to belong to
      the Leishmania donovani complex by kDNA PCR. Isoenzyme typing of three isolates
      revealed that they were identical to the L. donovani MON-82 reference strain, and
      the gp63 PCR-RFLP profile showed similar patterns to a reference strain of MON
      82. CL is endemic in most regions of Sudan and has been reported previously as
      being caused by L. major MON-74. The results of this study suggest that L.
      donovani is also a cause of CL in Sudan and that further study of isolates from
      Sudanese patients with cutaneous ulcers is warranted to ascertain whether L.
      donovani or L. major is the causative agent.

PMID- 18037150
TI  - Gene expression in endometrial cancer cells (Ishikawa) after short time high dose
      exposure to progesterone.
AB  - The potent antiproliferative effect of progestins has been utilized in clinical
      regimens for treatment of endometrial proliferative disorders. The progestin
      infiltrated intrauterine device used as therapy for endometrial carcinoma as well
      as endometrial hyperplasia yields a hundred-fold increase of local progestin
      concentration in the endometrium compared to that of oral treatment. The genetic
      basis for the complex effects of high dose progestins and the different
      signalling pathways regulated by these genes have never been accurately surveyed.
      The aim of the present study was to determine the gene expression pattern in
      highly differentiated endometrial cancer cells (Ishikawa) after short time
      exposure to high progesterone doses. In eight independent experiments, cells were
      treated with progesterone (30microg/ml) for 4h and gene expression was compared
      to that of untreated cells, which served as controls. Microarray analysis
      revealed 247 differentially expressed genes of which 126 were up-regulated and
      121 were down-regulated. Of these, 135 genes are known to be involved in
      biological processes like cell cycle, cell proliferation and differentiation,
      developmental processes, immune responses, intracellular protein traffic and
      transport. Our study shows that microarray analysis can detect relevant gene
      expression changes in endometrial cells treated with progestin, including those
      involved in several alternative transcriptional factors and signalling pathways.
      Many of the differentially expressed genes were not previously known to be
      affected by progesterone or have unknown biological functions. Characterization
      of these genes may give new insights into molecular responses to treatment with
      high progesterone doses. Alternative signalling pathways for progesterone, rather
      than the classical steroid receptors pathways are also suggested.

PMID- 18037152
TI  - Polymeric black tea polyphenols inhibit 1,2-dimethylhydrazine induced colorectal
      carcinogenesis by inhibiting cell proliferation via Wnt/beta-catenin pathway.
AB  - Tea polyphenols like epigallocatechin gallate and theaflavins are established
      chemopreventive agents for colorectal carcinogenesis. However, studies on
      evaluating similar chemopreventive properties of thearubigins or polymeric black
      tea polyphenols (PBPs), the most abundant polyphenols in black tea, are limited.
      Hence, in the present study we aim to investigate chemopreventive effects along
      with probable mechanisms of action of PBP extract employing 1,2-dimethylhydrazine
      (DMH)-induced colorectal carcinogenesis in Sprague-Dawley rats as experimental
      model. The present study suggests that PBPs, like other tea polyphenols, also
      inhibit DMH-induced colorectal tumorigenesis by decreasing tumor volume and
      multiplicity. This study also shows that although the pretreatment with PBP
      extract could induce detoxifying enzymes in hepatic and colorectal tissue, it did
      not show any additional chemopreventive effects when compared to treatments with
      PBP extract after initiation with DMH. Mechanistically, PBP extract may inhibit
      colorectal carcinogenesis by decreasing DMH-induced cell proliferation via
      Wnt/beta-catenin pathway. Treatments with PBP extract showed decreased levels of
      COX-2, c-MYC and cyclin D1 proteins which aid cell proliferation probably by
      regulating beta-catenin by maintaining expression of APC and decreasing
      inactivation of GSK3beta. DMH-induced activation of MAP kinases such as ERK and
      JNK was also found to be inhibited by treatments with PBP extract. In conclusion,
      the protective effects of PBP extract could be attributed to inhibition of DMH
      induced cellular proliferation probably through beta-catenin regulation.

PMID- 18037151
TI  - Risks and benefits of commonly used herbal medicines in Mexico.
AB  - In Mexico, local empirical knowledge about medicinal properties of plants is the
      basis for their use as home remedies. It is generally accepted by many people in
      Mexico and elsewhere in the world that beneficial medicinal effects can be
      obtained by ingesting plant products. In this review, we focus on the potential
      pharmacologic bases for herbal plant efficacy, but we also raise concerns about
      the safety of these agents, which have not been fully assessed. Although numerous
      randomized clinical trials of herbal medicines have been published and systematic
      reviews and meta-analyses of these studies are available, generalizations about
      the efficacy and safety of herbal medicines are clearly not possible. Recent
      publications have also highlighted the unintended consequences of herbal product
      use, including morbidity and mortality. It has been found that many
      phytochemicals have pharmacokinetic or pharmacodynamic interactions with drugs.
      The present review is limited to some herbal medicines that are native or
      cultivated in Mexico and that have significant use. We discuss the cultural uses,
      phytochemistry, pharmacological, and toxicological properties of the following
      plant species: nopal (Opuntia ficus), peppermint (Mentha piperita), chaparral
      (Larrea divaricata), dandlion (Taraxacum officinale), mullein (Verbascum
      densiflorum), chamomile (Matricaria recutita), nettle or stinging nettle (Urtica
      dioica), passionflower (Passiflora incarnata), linden flower (Tilia europea), and
      aloe (Aloe vera). We conclude that our knowledge of the therapeutic benefits and
      risks of some herbal medicines used in Mexico is still limited and efforts to
      elucidate them should be intensified.

PMID- 18037153
TI  - Properties and cDNA cloning of antihemorrhagic factors in sera of Chinese and
      Japanese mamushi (Gloydius blomhoffi).
AB  - An antihemorrhagic protein has been isolated from the serum of Chinese mamushi
      (Gloydius blomhoffi brevicaudus) by using a combination of ethanol precipitation
      and a reverse-phase high-performance liquid chromatography (HPLC) on a C8 column.
      This protein-designated Chinese mamushi serum factor (cMSF)-suppressed mamushi
      venom-induced hemorrhage in a dose-dependent manner. It had no effect on trypsin,
      chymotrypsin, thermolysin, and papain but inhibited the proteinase activities of
      several snake venom metalloproteinases (SVMPs) including hemorrhagic enzymes
      isolated from the venoms of mamushi and habu (Trimeresurus flavoviridis). A
      similar protein (Japanese MSF, jMSF) with antihemorrhagic activity has also been
      purified from the sera of Japanese mamushi (G. blomhoffi). The N-terminal 70 and
      51 residues of the intact cMSF and jMSF were directly analyzed; a similarity
      between the sequences of two MSFs to that of antihemorrhagic protein (HSF) from
      habu serum was noticed. To obtain the complete amino acid sequences of MSFs,
      cDNAs encoding these proteins were cloned from the liver mRNA of Chinese and
      Japanese vipers based on their N-terminal amino acid sequences. The mature forms
      of both MSFs consisted of 305 amino acids with a 19-residue signal sequence, and
      a unique 17-residue deletion was detected in their His-rich domains.

PMID- 18037154
TI  - Constitutive expression of thymidylate synthase from LCDV-C induces a transformed
      phenotype in fish cells.
AB  - Thymidylate synthase (TS), an essential enzyme in DNA synthesis and repair, plays
      a key role in the events of cell cycle regulation and tumor formation. Here, an
      investigation was presented about subcellular location and biological function of
      viral TS from lymphocystis disease virus from China (LCDV-C) in fish cells.
      Fluorescence microscopy revealed that LCDV-C TS was predominantly localized in
      the cytoplasm in fish cells. Cell cycle analysis demonstrated that LCDV-C TS
      promoted cell cycle progression into S and G2/M phase in the constitutive
      expressed cells. As a result, the cells have a faster growth rate compared with
      the control cells as revealed by cell growth curves. For foci assay, the TS
      expressed cells gave rise to foci 4-5 weeks after incubation. Microscopic
      examination of the TS-induced foci revealed multilayered growth and crisscross
      morphology characteristic of transformed cells. Moreover, LCDV-C TS predisposed
      the transfected cells to acquire an anchorage-independent phenotype and could
      grow in 0.3% soft agar. So the data reveal LCDV-C TS is sufficient to induce a
      transformed phenotype in fish cells in vitro and exhibits its potential ability
      in cell transformation. To our knowledge, it is the first report on viral TS
      sequences associated with transforming activity.

PMID- 18037155
TI  - Human immunodeficiency virus 1 (HIV-1) virion infectivity factor (Vif) is part of
      reverse transcription complexes and acts as an accessory factor for reverse
      transcription.
AB  - Virion infectivity factor (Vif) facilitates HIV infection by counteracting
      APOBEC3G late in replication in virus-producer cells. Here, we show that early
      after infection of new target cells Vif is part of the HIV reverse transcription
      machinery and acts as an accessory factor for reverse transcription. Vif protein
      was present in gradient fractions containing reverse transcription complexes
      (RTCs), and anti-Vif antibody immunoprecipitated HIV reverse transcription
      products from these gradient fractions. To investigate a role for Vif in RTCs
      independent of APOBEC3G, we created an intracellular environment that would
      restrict reverse transcription by pre-treating permissive target cells with 5
      Fluoro 2-deoxyuridine, a thymidylate synthetase inhibitor, prior to infection
      with virus from permissive cells. Infectivity assays and quantitation of reverse
      transcription products demonstrated that replication of HIV lacking Vif was
      inhibited to a greater degree than wild type, without concurrent mutation of
      reverse transcription products, suggesting compromised reverse transcription in
      the absence of Vif.

PMID- 18037156
TI  - Tetrabromobisphenol A (TBBPA) and hexabromocyclododecanes (HBCDs) in tissues of
      humans, dolphins, and sharks from the United States.
AB  - Concentrations of tetrabromobisphenol A (TBBPA) and alpha-, beta-, and gamma
      isomers of hexabromocyclododecanes (HBCDs) were determined by liquid
      chromatography-tandem mass spectrometry (LC-ESI-MS/MS) in human adipose tissue
      obtained in New York City, and in three marine top-level predators--bottlenose
      dolphin, bull shark, and Atlantic sharpnose shark--collected from coastal waters
      of Florida, USA. The overall mean concentrations (mean+/-SD) of TBBPA and HBCDs
      were 0.048+/-0.102 and 0.333+/-0.571 ng/g lipid wt in human adipose tissue
      samples, 1.2+/-3 and 7.38+/-18 ng/g lipid wt in bottlenose dolphin blubber, 9.5+/
      12 and 77.7+/-128 ng/g lipid wt in bull shark muscle, and 0.872+/-0.5 and 54.5+/
      88 ng/g lipid wt in Atlantic sharpnose shark muscle. Overall mean concentrations
      of HBCDs were 5-10-fold higher than mean TBBPA concentrations, in all of the
      samples analyzed. The highest concentrations of TBBPA and HBCDs were detected in
      the bull shark muscle at concentrations of 35.6 and 413 ng/g, lipid wt,
      respectively. Concentrations of TBBPA and HBCDs, after log-transformation, were
      significantly correlated with each other in human adipose tissue and bottlenose
      dolphin blubber, but not in bull shark muscle samples. In the human adipose
      tissue samples, the concentrations of HBCDs were 3-4 orders of magnitude lower
      than the concentrations of polybrominated diphenyl ethers (PBDEs) previously
      reported for the same set of tissue samples. Concentrations of HBCDs in human
      samples from the United States were 1-5-fold lower than the concentrations
      reported from several European countries. HBCD concentrations in bottlenose
      dolphins from the United States were 1-2 orders of magnitude lower than the
      concentrations reported for other cetacean species from Europe. The present
      report is the first to determine levels of TBBPA and HBCDs in humans, bottlenose
      dolphins, and sharks from the United States.

PMID- 18037157
TI  - Enhancing polychlorinated biphenyl dechlorination in fresh water sediment with
      biostimulation and bioaugmentation.
AB  - Polychlorinated biphenyls (PCBs) are toxic compounds ubiquitously distributed in
      ecosystems. Microbial attenuation of these contaminants is a potential means of
      remediation. Two promising microbial PCB remediation technologies, biostimulation
      and bioaugmentation, were investigated in different sediments. Biostimulation
      experiments in which electron donor was supplied (H2 via elemental iron, Fe(0))
      resulted in only a marginal improvement in the dechlorination of amended 2,3,4,5
      tetrachlorobiphenyl (2,3,4,5-CB), likely because of an inadequate population of
      indigenous H2-utilizing dechlorinators. Extensive dechlorination was observed,
      however, after bioaugmenting microcosms with a PCB-dechlorinating enrichment
      culture. Dechlorination of 2,3,4,5-CB began prior to the 20th day of incubation
      and proceeded to 2-chlorobiphenyl. This extensive dechlorination activity was
      maintained in both sediments over 70d at 10 and 25 degrees C. This research
      demonstrates that although past studies of biostimulation were promising, a great
      deal must be known about the PCB-dechlorinating organisms present before
      successful biostimulation is expected. Bioaugmentation, however, appears to be a
      promising PCB remediation strategy and should be further pursued.

PMID- 18037158
TI  - Prognostic significance of CD3+ tumor-infiltrating lymphocytes in ovarian
      carcinoma.
AB  - OBJECTIVE: Epithelial ovarian cancer (EOC) is the most common cause of death
      among gynecological malignancies in Europe and North America. Although the
      presence of tumor-infiltrating mononuclear cells has been documented in EOC, the
      association of tumor-infiltrating mononuclear cells with clinical outcome remains
      controversial. The aim of the present study was to investigate the prognostic
      significance of CD3+ tumor-infiltrating T lymphocytes (TIL) on overall survival
      of EOC patients. METHODS: We evaluated retrospectively by immunohistochemistry
      the distribution of CD3+ TIL in tumor specimens of 116 EOC patients. The
      expression of estrogen and progesterone receptors, Ki-67, DNA topoisomerase
      IIalpha, p21, p53, HER-2/neu, bax and bcl-2 was also evaluated by
      immunohistochemistry. The prognostic significance of CD3+ TIL and other
      immunohistochemical and clinical parameters was evaluated with log-rank test.
      Multivariate analysis was performed using the Cox regression. RESULTS: CD3+ TIL
      were observed in all tumor samples, both in cancer stroma and within cancer
      epithelium (intraepithelial TIL). The median counts of stromal TIL and
      intraepithelial TIL were 338 lymphocytes/mm2 (range 81-2094 lymphocytes/mm2) and
      125 lymphocytes/mm2 (range 7-481 lymphocytes/mm2), respectively. In univariate
      analysis, age, stage, grade, presence of residual tumor, expression of
      progesterone receptors, Ki-67, DNA topoisomerase IIalpha and intraepithelial CD3+
      TIL count were significant predictors of overall survival. On multivariate
      analysis, only the presence of residual tumor, stage, expression of progesterone
      receptors and intraepithelial CD3+ TIL count were found to be significant
      independent predictors of overall survival. CONCLUSION: Present data indicate
      that the intraepithelial CD3+ TIL count is a significant prognostic factor in
      EOC.

PMID- 18037159
TI  - Angiopoietin-2 as a contributing factor of exercise-induced bronchoconstriction
      in asthmatic patients receiving inhaled corticosteroid therapy.
AB  - BACKGROUND: Airway microcirculation has the potential to contribute to the
      pathogenesis of exercise-induced bronchoconstriction (EIB) in asthma. Recently,
      angiopoietin-1 has been found to stabilize microvessels and make them leak
      resistant, whereas angiopoietin-2 is an antagonist of angiopoietin-1 and enhances
      microvascular permeability. OBJECTIVE: We sought to examine the roles of
      angiopoietin-2 in EIB in asthmatic patients with inhaled corticosteroid therapy.
      METHODS: Levels of angiopoietin-1 and angiopoietin-2 in induced sputum were
      examined in 32 asthmatic patients who were receiving inhaled corticosteroid
      therapy for more than 6 months at the entry of this study and 14 healthy control
      subjects. All asthmatic patients performed an exercise test. RESULTS: The degree
      of eosinophilic airway inflammation did not differ significantly between
      asthmatic patients and healthy control subjects. Angiopoietin-1 levels were also
      similar in the 2 groups (asthmatic patients: median, 6.0 ng/mL [range, 2.0-10.7
      ng/mL]; healthy control subjects: median, 4.2 ng/mL [range, 1.5-10.7 ng/mL]). In
      contrast, angiopoietin-2 levels were significantly higher in asthmatic patients
      than in healthy control subjects (asthmatic patients: median, 0.74 ng/mL [range,
      0.3-1.2 ng/mL]; healthy control subjects: median, 0.26 ng/mL [range, 0.05-0.47
      ng/mL]; P < .001). There was no significant correlation between angiopoietin-1
      levels and the severity of EIB in asthmatic patients. However, angiopoietin-2
      levels were significantly correlated with the severity of EIB and airway
      microvascular permeability index. CONCLUSION: Angiopoietin-2 levels were
      increased in the airways of asthmatic patients with inhaled corticosteroid
      therapy, and its levels were associated with the severity of EIB.

PMID- 18037160
TI  - Mycobacterium bovis BCG killed by extended freeze-drying reduces airway
      hyperresponsiveness in 2 animal models.
AB  - BACKGROUND: Live BCG administered intranasally to mice inhibits the development
      of ovalbumin (OVA)-induced eosinophilia and airway hyperresponsiveness (AHR). It
      is unacceptable to treat human subjects intranasally with live BCG. OBJECTIVE: We
      investigated whether BCG killed by extended freeze-drying (EFD) and
      subcutaneously injected has a protective effect in murine and guinea pig models
      of allergic airway inflammation. METHODS: Mice were OVA sensitized (days 0 and
      7), treated subcutaneously (day 14) with EFD and live or heat-killed BCG, and
      then OVA challenged (day 42). OVA-sensitized mice (days 0 and 7) were challenged
      (day 14) and EFD treated (day 18) before OVA rechallenge (day 46) to demonstrate
      the capacity of EFD to reverse the established lung inflammation. Guinea pigs
      were OVA sensitized (days 0 and 14), treated intradermally (day 35) with EFD, and
      OVA challenged (days 90-105). RESULTS: In mice and guinea pigs EFD treatment
      reduced AHR. Among 3 BCG preparations, only EFD efficiently reduced AHR,
      eosinophilia, and the recruitment of dendritic cells to the lungs after OVA
      challenge. The protective effect of EFD is associated with production of the
      immunoregulatory cytokine IL-10. Moreover, EFD treatment did not induce toxic
      effects or delayed-type hypersensitivity to mycobacterial antigens; that is, it
      did not interfere with the diagnosis of tuberculosis. CONCLUSION: EFD
      administered subcutaneously inhibits the development of allergic airway
      inflammation and prevents AHR without inducing delayed-type hypersensitivity and
      side effects associated with live or heat-killed BCG.

PMID- 18037161
TI  - Molecular and functional analysis of the antigen receptor of Art v 1-specific
      helper T lymphocytes.
AB  - BACKGROUND: Ninety-five percent of patients with mugwort allergy are sensitized
      to Art v 1, the sole major allergen in mugwort (Artemisia vulgaris) pollen. Sixty
      nine percent of patients recognizing the single immunodominant T-cell epitope Art
      v 1(25-36) have an HLA-DRB1*01 phenotype. OBJECTIVE: We studied cloning and
      functional expression of a human alphabeta T-cell receptor (TCR) specific for Art
      v 1(25-36). METHODS: TCR chains were RT-PCR amplified from an Art v 1(25-36)
      specific T-cell clone, retrovirally transferred, and functionally tested in
      Jurkat T cells or alternatively in peripheral blood T lymphocytes of nonallergic
      individuals. RESULTS: The alpha-chain of the TCR is composed of TRAV17 and TRAJ45
      segments, and the beta-chain uses TRBV18, TRBD1, and TRBJ2-7. Analyses of 23
      other Art v 1-specific T-cell clones did not reveal preferential usage of the
      TRAV17, TRBV18, or other TCR gene families. Efficient TCR transfer into Jurkat T
      cells was shown by binding of TCR Vbeta18-specific mAb and DRB1*0101/Art v 1
      tetramers. Transgenic Jurkat T cells specifically recognized syngeneic EBV B
      cells pulsed with Art v 1(25-36) peptide and artificial antigen-presenting cells
      expressing invariant chain::Art v 1 fusion proteins. Moreover, transfer of the
      TCR into peripheral blood lymphocytes generated T cells that were Art v 1
      reactive. Activation of transgenic T cells by artificial antigen-presenting cells
      was strictly dependent on costimulation. CONCLUSION: For the first time, a
      detailed molecular and functional analysis of a human allergen-specific TCR is
      presented.

PMID- 18037162
TI  - Patterns of GATA3 and IL13 gene polymorphisms associated with childhood rhinitis
      and atopy in a birth cohort.
AB  - BACKGROUND: GATA3 activates transcription of the T(H)2 cytokines, including IL13,
      an important step in the allergic inflammatory pathway. OBJECTIVE: We sought to
      identify associations of single nucleotide polymorphisms of the genes GATA3 and
      IL13 and their interactions with rhinitis and allergic sensitization during
      childhood. METHODS: We performed genetic association studies in a cohort of
      children (n = 923) who have been evaluated for the development of rhinitis and
      allergic sensitization by means of skin prick tests (SPTs) at age 10 years.
      Pyrosequencing was used to genotype 7 polymorphisms from GATA3 and 5 from IL13. A
      novel model-selection procedure combining logistic regression models and
      classification was used to study the contributions of the polymorphisms and their
      interactions. RESULTS: Combinations of polymorphisms and their interactions
      increase the risk for rhinitis and allergic sensitization at age 10 years. A
      model with rs1058240, rs379568, and rs4143094 (GATA3) and rs1800925 (IL13) and
      their interactions was selected to predict rhinitis and positive SPT responses.
      rs1058240 was associated with rhinitis and allergic rhinitis (P < .05), and the
      gene-gene interaction rs1058240:rs1800925 was associated with rhinitis (P =
      .043). The odds ratios for 4 genotype combinations were significant for rhinitis
      or SPTs (P < .044). CONCLUSION: Gene-gene interaction between GATA3 and IL13
      polymorphisms can influence the risk of childhood rhinitis. Our study suggests
      that set associations of polymorphisms are important in studying genetic
      associations for complex phenotypes, such as rhinitis and atopy.

PMID- 18037164
TI  - Advantages of human umbilical vein scaffolds derived from cesarean section vs.
      vaginal delivery for vascular tissue engineering.
AB  - The current study investigated whether the mode of delivery and the mode of
      sample collection affect the functional properties of umbilical veins as
      scaffolds for vascular tissue engineering purposes. Human umbilical vein (HUV)
      from planned cesarean-sections (PCS) showed a 1.7-fold higher maximum contraction
      with potassium chloride compared to spontaneous vaginal deliveries (VDs,
      p=0.029). The maximum contractions with histamine were 2.0- and 2.9-fold higher
      in the PCS and emergency c-section (ECS) groups, respectively, compared to the VD
      group (p=0.003). The dose-response curves of serotonin were shifted to the right
      approx. 6- and 5-fold in the VD group compared to PCS and ECS, respectively
      (p=0.009). There were no differences between the birth groups in terms of
      tetrazolium dye reduction, platelet adhesion, and the structural integrity. The
      release of the antithrombotic compound prostacyclin from vessels of the PCS and
      ECS groups was 6.6- and 3.5-fold higher, respectively, than in the VD group
      (p<0.001). There was no correlation between the duration of ischemia and any of
      the functional parameters. This study provides evidence that vessels obtained
      from PCS are to be preferred for tissue engineering purposes, as they can be
      harvested in a sterile fashion and show superior vasoconstrictor responses and
      antithrombotic properties. The data also support a once-per-day pickup schedule
      for umbilical cords without a deterioration of the functional properties.

PMID- 18037163
TI  - Peptide- and collagen-based hydrogel substrates for in vitro culture of chick
      cochleae.
AB  - The overall goal of this work is to improve the culture of the auditory organ of
      birds for the dual use of developing a hair cell regeneration model and charting
      a pathway to the eventual replacement of the hearing organ. In doing so, we
      develop a protocol for removing the auditory organ from its basement membrane in
      the inner ear, attach the organ to a series of artificial basement membranes, and
      conduct qualitative and quantitative analysis of how cell morphology, viability
      and function change with time. Native matrix cultures, where the epithelium was
      floating in media with the basement membrane and accessory structures attached,
      were used as a basis of comparison. PuraMatrix, collagen I, collagen
      I/chondroitin-sulfate and Matrigel were chosen to encompass a diverse range of
      mechanical properties and macromolecule moieties. Surprisingly, we find that
      PuraMatrix outperformed the other matrices as a scaffold for sensory organ
      culture. PuraMatrix a self-assembled peptide hydrogel, is a biochemically
      specific culture substrate that contains none of the extracellular matrix (ECM)
      molecules and growth factors contained in the inner ear's basement membrane.
      Rheological measurements reveal that PuraMatrix may be a closer approximation to
      the stiffness of the soft tissue supporting the auditory organ. Cell density on
      the PuraMatrix substrate is comparable to that of the native matrix cultures,
      despite the absence of the basement membrane and accessory structures. Further
      studies show that PuraMatrix supports the culture of functional hair cells over a
      72 h period, with a significant increase in the number of functional hair cells
      in comparison to the organ cultured without a matrix. This is the first example
      of adhesion of the adult auditory epithelium to a biomaterial for an extended
      period of time. With further optimization, this system will enable the
      performance of many novel biophysical and pharmacological studies involving hair
      cells and supporting cells.

PMID- 18037165
TI  - Gestational diseases -- a workshop report.
AB  - Between 11% and 20% of all clinically recognised pregnancies are lost before the
      20th week of gestation, with huge financial and personal implications. Immune
      mechanisms have been proposed to play a role in unexplained recurrent
      miscarriage. Considerable attention has focused on endometrial leucocyte
      populations in recurrent miscarriage, although the underlying pathogenesis
      remains largely unexplained. The mechanisms underlying sporadic miscarriage are
      even less well understood, although aneuploidy is the commonest attributable
      cause of early (<or=12 completed weeks gestation) sporadic miscarriage.
      Hydatidiform mole is a rare cause of early pregnancy loss with marked
      geographical variation in incidence. Both complete and partial hydatidiform mole
      are associated with excessive trophoblast proliferation and hence provide an
      opportunity to study trophoblast growth regulation.

PMID- 18037166
TI  - Antiretroviral therapy in AIDS patients with CMV disease: impact on the survival
      and long-term treatment outcome.
AB  - OBJECTIVES: To determine the impact of antiretroviral therapy (ART) on the long
      term survival of AIDS patients with CMV disease and evaluate long-term outcomes
      of ART. METHODS: A retrospective cohort study was conducted among HIV-infected
      patients with CMV disease in a medical school hospital during 1996-2005 and
      followed-up until June 2007. RESULTS: There were 154 patients, mean age 34.5
      years and 57.8% were male. Organ involvement of CMV disease included retina
      (94.8%), central nervous system, lungs, and gastrointestinal tract. Median CD4
      cell count was 20 cells/mm(3) and 99 patients received ART. During median follow
      up of 32 months (interquartile range 23-96), 29.2% of patients died. From Kaplan
      Meier analysis, median survival is significantly longer in patients receiving ART
      (>116.2 vs. 21.6 months, log-rank test, p<0.001). From Cox's proportional hazard
      model, ART (HR 0.6, p<0.001) and previous opportunistic infections (HR 3.5,
      p=0.025) were negatively and positively associated with death, respectively. At
      median time of 69 months (interquartile range 34-101) in patients who received
      ART, 80.8% had HIV-1 RNA <50 copies/mL and median CD4 was 421 cells/mm(3). One
      patient had immune reconstitution syndrome at 3 months after initiation of ART
      and resulted in permanent vision loss. CONCLUSIONS: ART significantly improves
      long-term survival of AIDS patients with CMV disease. Long-term virological and
      immunological outcomes are durable.

PMID- 18037167
TI  - Separation anxiety in first-time mothers: infant behavioral reactivity and
      maternal parenting self-efficacy as contributors.
AB  - This short-term longitudinal study examined the contribution of infant behavioral
      reactivity and maternal parenting self-efficacy to first-time mothers' (total
      n=32) separation anxiety. Infants' behavioral reactivity indexed by gaze and
      facial affect were observed in the conditions of routine play and maternal still
      face at 3 months. Mothers reported their self-perceived parenting efficacy at 3
      months and separation anxiety at 6 months. Results revealed that infants'
      frequent gazing at their mother, greater negative affect, and less positive
      affect observed during the still face, but not during the routine play,
      contributed to heightened maternal separation anxiety. In addition to a direct
      link between low maternal parenting self-efficacy and high maternal separation
      anxiety, maternal parenting self-efficacy buffered against the impact of infant
      negative reactivity on maternal separation anxiety. The role of infant reactivity
      and maternal self-efficacy in parenting was discussed.

PMID- 18037168
TI  - Delivering growth factors for therapeutics.
AB  - The method by which a drug is released can have a significant effect on
      therapeutic efficacy. The mode of drug delivery is especially relevant when the
      therapeutic agent is a growth factor because the dose and spatiotemporal release
      of such agents at the site of injury is crucial to achieving a successful
      outcome. Here, we highlight delivery technologies designed to facilitate the
      local and controlled spatiotemporal release of growth factors through the use of
      biomaterials, 3D micro- or nano-particles, microspheres, gene therapy and PRGF
      technology. We present some of the most interesting therapeutic applications
      based on these approaches and, on PRGF technology in particular, in addition to
      the limitations, future challenges and directions of the field.

PMID- 18037169
TI  - FDA perspective on antivirals against biothreats: communicate early and often.
AB  - Development of antiviral products for certain highly pathogenic viruses with
      limited available treatments, such as viruses that may have biothreat potential,
      is critically important and challenging. The mission of the FDA is to protect the
      public health by assuring the safety, efficacy and quality of such products.
      Human clinical trials are critically important whenever relevant naturally
      occurring diseases can appropriately be studied. In selected situations when
      clinical studies are not ethical and field efficacy studies are not feasible, the
      Animal Rule (67 FR 37988, 2002) introduces the possibility of drug/biologic
      approval/licensure based on efficacy studies in animals, and appropriate human
      safety and pharmacokinetic information. This approach necessitates the
      development of well-delineated animal models predictive of human disease and
      treatment responses, and plans for adding human information if suitable
      circumstances arise. Efficient development of therapeutics against these agents
      requires collaborative efforts among industry, academia and federal agencies.

PMID- 18037170
TI  - D2 receptor density and prepulse inhibition in humans: negative findings from a
      molecular genetic approach.
AB  - There is plenty of evidence from schizophrenia research and psychopharmacological
      experiments showing the influence of the dopaminergic neurotransmission on the
      prepulse inhibition (PPI). A lot of insights into the underlying neural
      mechanisms of the PPI have been gained from animal models, which are in need to
      be validated in humans. Due to new technological advances, findings from
      psychopharmacological challenge tests can now be verified with techniques from
      molecular genetics which provide an elegant non-invasive approach. To close the
      gap between animal research and research in humans in this field a molecular
      genetic approach was applied to investigate the neural mechanisms of the PPI in
      healthy subjects. In N=96 female participants recruited out of a sample of N=800
      subjects according to their genotypes we tested the association between the DRD2
      Taq Ia and the COMT Val158Met polymorphisms, and the magnitude of the eye-blink
      reflex in an acoustic PPI paradigm. Neither significant influences of both
      dopaminergic single nucleotide polymorphisms nor an epistasis effect could be
      detected. Although findings do not support the hypothesis that two of the most
      prominent dopaminergic candidate loci (DRD2 Taq Ia and COMT Val158Met) effect PPI
      the study does not exclude the relevance of the dopaminergic system in general.
      Further molecular genetic studies investigating other variants on dopaminergic
      genes have to be conducted.

PMID- 18037171
TI  - Efficacy of antipsychotics to reverse phencyclidine-induced social interaction
      deficits in female rats--a preliminary investigation.
AB  - Sub-chronic phencyclidine (PCP) treatment mimics certain aspects of schizophrenia
      symptomology in rats. However, there is a marked lack of attempts to model
      negative symptomology such as social behaviour deficits in female rats. This
      study was conducted to assess whether sub-chronic PCP treatment produces social
      interaction deficits in female rats and to ascertain if these deficits can be
      reversed by either typical (haloperidol) or atypical (clozapine and ziprasidone)
      antipsychotics.

PMID- 18037172
TI  - Time pressure leads to inhibitory control deficits in impulsive violent
      offenders.
AB  - Impulsive violent criminal behavior is often ascribed to problems with behavioral
      control. Such behavior could be a consequence of stronger pre-potent responses or
      a failure of inhibitory control. A countermanding task which allows dissociation
      of these two processes was used to examine whether impulsive violent offenders
      were found to exhibit impaired inhibitory control. An experiment with a time
      restriction on responding was performed to effectively limit the ability of the
      subjects to strategically control their error rate. The results showed that the
      performance of the impulsive violent offenders was only impaired in the time
      pressure condition. These findings suggest that impulsive violent behavior may be
      linked to abnormal modulation of the frontal cortical areas, areas thought to be
      involved in response inhibition by negative feedback or emotional responses,
      rather than frontal dysfunction per se.

PMID- 18037173
TI  - The differential effects of cervical and thoracic dorsal funiculus lesions in
      rats.
AB  - The purpose of this research was to compare the locomotor abilities of rats with
      cervical dorsal spinal funicular (DF) lesions to those of rats with the same
      lesion at the mid-thoracic level. The dorsal funiculus, consisting of ascending
      sensory fibers and the main component of the corticospinal tract, was transected
      either at spinal level C2 or at T8. We examined limb force generation and limb
      timing and coordination during overground locomotion, as well as foot placement
      errors during locomotion over a horizontal ladder. At 6 weeks post-surgery,
      bilateral lesions of the cervical DF caused subtle but persistent changes in the
      generation of ground reaction forces and limb timing during overground
      locomotion, and caused persistent forelimb, but not hindlimb, errors during
      ladder crossing. In contrast, the same lesion at the mid-thoracic level did not
      affect overground locomotion and caused only minor forelimb and hindlimb errors
      during ladder walking at 2 weeks post-lesion which recovered to pre-surgical
      levels by 6 weeks post-lesion. DF lesions at cervical vs. thoracic levels thus
      have differential effects on locomotor abilities in rats. We compare these
      results with previous work and suggest that the differential response to DF
      transection might be related to both functional distinctions between the fore-
      and hindlimbs and to anatomical differences in the dorsal funiculi at different
      spinal levels. These findings have implications for the mechanisms of recovery as
      well as the types of behavioural tests which can be practically used to measure
      functional changes in different lesion models.

PMID- 18037174
TI  - Steroid treatment deteriorated ventricular tachycardia in a patient with right
      ventricle-dominant cardiac sarcoidosis.
AB  - We report a case of a patient with cardiac sarcoidosis presenting with a non
      sustained ventricular tachycardia (VT), mimicking arrhythmogenic right
      ventricular cardiomyopathy. After the pathological diagnosis and confirmation of
      gallium-67 uptake by the myocardium, corticosteroid therapy was initiated. The
      myocardial gallium accumulation disappeared shortly after the treatment, but the
      VTs deteriorated into multifocal and sustained VTs almost all day. Those drug
      refractory VTs were finally controlled with 3 catheter ablation sessions.

PMID- 18037175
TI  - Potential of sponges and microalgae for marine biotechnology.
AB  - Marine organisms can be used to produce several novel products that have
      applications in new medical technologies, in food and feed ingredients and as
      biofuels. In this paper two examples are described: the development of marine
      drugs from sponges and the use of microalgae to produce bulk chemicals and
      biofuels. Many sponges produce bioactive compounds with important potential
      applications as medical drugs. Recent developments in metagenomics, in the
      culturing of associated microorganisms from sponges and in the development of
      sponge cell-lines have the potential to solve the issue of supply, which is the
      main limitation for sponge exploitation. For the production of microalgal
      products at larger scales and the production of biofuels, major technological
      breakthroughs need to be realized to increase the product yield.

PMID- 18037176
TI  - Enzymes go big: surface hydrolysis and functionalization of synthetic polymers.
AB  - Enzyme technology has progressed from the biotransformation of small substrates
      to biotransformation of synthetic polymers. Important breakthroughs have been the
      isolation and design of novel enzymes with enhanced activity on synthetic polymer
      substrates. These were made possible by efficient screening procedures and
      genetic engineering approaches based on an in-depth understanding of the
      mechanisms of enzymes on synthetic polymers. Enhancement of the hydrophilicity of
      synthetic polymers is a key requirement for many applications, ranging from
      electronics to functional textile production. This review focuses on enzymes that
      hydrolyse polyalkyleneterephthalates, polyamides or polyacrylonitriles,
      specifically on the polymer surface thereby replacing harsh chemical processes
      currently used for hydrophilisation.

PMID- 18037177
TI  - A better fluorescent protein for whole-body imaging.
AB  - Whole-body imaging with fluorescent proteins is a powerful technology with many
      applications in small animals. Brighter, red-shifted proteins can make whole-body
      imaging more sensitive owing to reduced absorption by tissues and less scatter. A
      new protein called Katushka has been isolated. It is the brightest known protein
      with emission at wavelengths longer than 620 nm. This new protein offers the
      potential for noninvasive whole-body imaging of numerous cellular and molecular
      processes in live animals.

PMID- 18037178
TI  - Novel tomato flavours introduced by plastidial terpenoid pathway engineering.
AB  - Until recently breeding efforts centred on high-yield production while
      sacrificing flavour and taste quality traits of mass produced food products, such
      as tomatoes. The recent publication of Davidovich-Rikanati et al. demonstrates
      the technical feasibility of the genetical engineering of pathways in tomato
      plants to modify their fruit flavour profile in a proof-of-concept approach. The
      reported work ranks among an increasing number of reported successful
      modifications of edible plants with a focus on the benefits to end-consumers.

PMID- 18037179
TI  - Artificial cells: building bioinspired systems using small-scale biology.
AB  - Artificial cells have generated much interest since the concept was introduced by
      Aleksandr Oparin in the 1920s, and they have had an impact on the pharmaceutical
      and biotechnology industry in various areas, including potential therapeutic
      applications. Here, we discuss the development of small-scale, bio-inspired
      artificial cell components that recreate the function of key cellular and
      physiological systems. We describe artificial cells, selected current
      applications and how small-scale biology could be used to provide what might be a
      next-generation approach in this area. We believe that this type of work is in
      its infancy and that exploiting small-scale biological inspiration in the field
      of artificial cells has great potential for successes in the future.

PMID- 18037180
TI  - Computed tomography for excision cavity localization and 3D-treatment planning in
      partial breast irradiation with high-dose-rate interstitial brachytherapy.
AB  - BACKGROUND AND PURPOSE: When high-dose-rate brachytherapy is used for partial
      breast irradiation (PBI) precise pre-implant definition of planning target volume
      (PTV) and implant geometry is required. After implantation, accurate PTV
      localization, catheter reconstruction and optimization of dose distribution are
      needed for good PTV coverage and dose conformity. We applied image-guidance using
      computed tomography (CT) for pre-implant PTV definition and post-implant
      dosimetry. MATERIALS AND METHODS: In 54 patients implant geometry was designed by
      external beam virtual simulation. A template was placed over dummy beam digitally
      reconstructed radiographs displaying PTV. Needle entrance and exit points were
      defined and marked on the patient's skin to serve as landmarks during
      implantation. After implantation, in 46/54 patients PTV was defined, catheters
      were reconstructed and active lengths in the catheters were specified using CT
      based-3D planning system. Dosimetry was performed with a Plato-Nucletron
      treatment planning system. RESULTS: Post-implantation CT visualized precise
      catheter placement with respect to the PTV in all patients. CT-based treatment
      planning provided good coverage of PTV and homogeneous dose distribution.
      CONCLUSIONS: In post-operative PBI with high-dose-rate brachytherapy CT-based pre
      implant definition of implant geometry ensures adequate PTV coverage. After
      implantation, CT-based 3D-treatment planning software ensures exact PTV
      localization and catheter reconstruction, and dose distribution optimization.

PMID- 18037181
TI  - Dosimetric experience with accelerated partial breast irradiation using image
      guided interstitial brachytherapy.
AB  - BACKGROUND AND PURPOSE: To present our dosimetric findings with image-guided high
      dose-rate interstitial brachytherapy of breast cancer. MATERIALS AND METHODS:
      Treatment plans of 28 patients with early-stage breast cancer treated with
      interstitial partial-breast irradiation were selected for the study. The total
      dose was 30.1Gy in 4.3-Gy fractions given twice daily. Before implantation all
      patients underwent CT imaging with the purpose of target volume definition and
      catheter placement planning. Postimplant CT scanning was done for dose planning.
      Geometrical and graphical optimizations were performed. Quantitative dosimetry on
      the target volume and critical structures was performed. Retrospectively,
      conformal dose plans using dose point optimization were made and compared with
      the treatment plans. RESULTS: Three-, four-, and five-plane implants were used in
      10, 13 and 5 patients, respectively. The median number of catheters was 14 (range
      8-22). The mean volume of the PTV was 63.1cm(3) (range 17.2-124cm(3)) and on
      average, 91% (range 90-96%) of the PTV received the reference dose. The mean
      minimum dose received by at least 90% of the PTV was 102% (range 99-107%) and the
      conformality index 0.68 (range 0.51-0.82). The dose non-uniformity ratio and dose
      homogeneity index for target were 0.33 (range 0.25-0.41) and 0.64 (range 0.50
      0.76), respectively. The mean maximum dose to skin, lung and heart was 53%, 42%
      and 21%, respectively. Volumes of the lung and heart receiving 5Gy were 42.6cm(3)
      and 8cm(3), respectively. CONCLUSIONS: Dosimetric results using our implant
      technique based on two sets of CT scanning seem to be acceptable with respect to
      target coverage, dose homogeneity and conformality.

PMID- 18037182
TI  - Heart and coronary artery protection in patients with mediastinal Hodgkin
      lymphoma treated with intensity-modulated radiotherapy: dose constraints to
      virtual volumes or to organs at risk?
AB  - BACKGROUND AND PURPOSE: To increase heart and coronary artery protection in
      patients with mediastinal Hodgkin lymphoma treated with intensity-modulated
      radiotherapy (IMRT). MATERIALS AND METHODS: Twenty patients with early-stage
      mediastinal Hodgkin lymphoma entered the study. IMRT was delivered to the
      initially involved lymph node volumes. Various virtual volumes (VVs) were
      designed to improve the protection of the heart and the origin of the coronary
      arteries, which were the organs at risk (OARs), while preserving adequate PTV
      coverage. The results obtained with VVs were then compared with those obtained
      with dose constraints assigned to OARs. RESULTS: The most satisfactory VV was
      obtained using the PTV expansion concept. The best compromise between adequate
      PTV coverage and OAR protection was obtained with dose constraints assigned to
      the PTV expansion VV and to the origin of the coronary arteries. CONCLUSIONS:
      IMRT can be improved by using dose constraints assigned to the PTV expansion VV
      and/or to the origin of the coronary arteries.

PMID- 18037183
TI  - A wide range of NS3/4A protease catalytic efficiencies in HCV-infected
      individuals.
AB  - The hepatitis C virus (HCV) NS3/4A protease acts as an antagonist of virus
      induced interferon (IFN) regulatory factor (IRF)-3 activation and IFN-beta
      expression. The NS3/4A protease performs this function by cleaving Cardif and
      TRIF proteins to block retinoic-acid-inducible gen I (RIG-I) and toll-like
      receptor (TLR)-3 signaling, respectively. NS3/4A protease inhibition can prevent
      Cardif and/or TRIF inactivation during HCV infection, thereby maintaining the
      innate immune response. Thus, differences in NS3/4A protease catalytic efficiency
      could be related to viral pathogenicity. In this study, we analyzed the catalytic
      efficiency of the most abundant NS3/4A protease isolated from each of 12
      individuals infected with HCV genotypes 1b, 1a, 3a, 4a or 4d. A diversity of
      NS3/4A protease catalytic efficiencies (up to a six-fold difference) was found in
      the analyzed samples. The genotype 1b NS3/4A proteases displayed the highest
      catalytic efficiencies. However, within this genotype up to three-fold
      differences were observed. Cross-genotypic interactions between the NS3 protease
      domain and the NS4A cofactor peptide were also investigated. Overall, catalytic
      efficiencies of NS3 proteases cross-interacting with NS4A cofactors from
      heterologous genotypes were as efficient as the homologous NS3/4A interactions.
      Of the 28 heterologous interactions tested, only 6 resulted in deleterious or
      nonfunctional enzymes. Nonfunctional interactions were not genotype-specific,
      suggesting that enhancement of NS3 catalytic efficiency by the NS4A cofactor
      depends on a few specific amino acid residues. Characterization of the
      proteolytic activities of individual NS3/4A proteases should provide clues for
      understanding HCV-host interactions, as well as assisting in the development of
      new classes of NS3/4A protease inhibitors.

PMID- 18037184
TI  - HA2-specific monoclonal antibodies as tools for differential recognition of
      influenza A virus antigenic subtypes.
AB  - Antigenic reactivity of a set of monoclonal antibodies (MAb) raised against the
      HA2 subunit of hemagglutinin of H3 subtype was characterized in a rapid culture
      assay. MAbs FC12 and FE1, known to recognize the same antigenic site (IV), cross
      reacted with influenza viruses of H3 and H4 subtypes, regardless of their host
      origin. No cross-reactivity was detected with other antigenic subtypes tested (H1
      H13). The involvement of conserved residues D160, N168, and F171 in the
      differential recognition of H3 and H4 subtypes is proposed. In contrast, MAb IIF4
      that recognizes antigenic site II exhibited a broader inter-subtype reactivity
      including subtypes H3, H4, H5, H8 and some viruses of H2, H6 and H13 subtypes.
      The ability of HA2-specific antibodies to differentially react with distinct
      antigenic subtypes can be utilized in development of diagnostics and in the
      influenza virus surveillance.

PMID- 18037185
TI  - Efficient targeting to alveolar macrophages by intratracheal administration of
      mannosylated liposomes in rats.
AB  - The success of targeting systems to alveolar macrophages critically depends on
      internalization into these cells for pharmacological intervention. Direct
      respiratory delivery via inhalation of mannose modified liposomal carriers to
      alveolar macrophages is of great interest. To evaluate the targeting efficiency
      to alveolar macrophages by intratracheal administration of mannosylated liposomes
      (Man-liposomes), Man-liposomes with various ratio of mannosylated cholesterol
      derivatives, cholesten-5-yloxy-N-(4-((1-imino-2-D
      thiomannosylethyl)amino)alkyl)formamide (Man-C4-Chol) as mannose receptor ligand
      were investigated with regard to their in vitro uptake in primary cultured
      alveolar macrophages and in vivo intratracheal administration in rats. The in
      vitro uptake of Man-liposomes took place in a concentration-dependent manner. The
      internalization of Man-liposomes with 7.5% (Man-7.5-liposomes) and 5.0% (Man-5.0
      liposomes) Man-C4-Chol was considerably higher than that of Man-liposomes with
      2.5% of Man-C4-Chol (Man-2.5-liposomes) and Bare-liposomes and significantly
      inhibited by an excess of mannan, suggesting mannose receptor-mediated
      endocytosis. After intratracheal administration of Man-7.5 and Man-5.0-liposomes
      in rats, a significantly high internalization and selective targeting to alveolar
      macrophages was observed. The enhanced cellular uptake in alveolar macrophages
      related to the mannose density of Man-liposomes was also confirmed both in vitro
      and in vivo confocal microscopy studies. These results demonstrate the efficient
      targeting to alveolar macrophages by the intratracheally administered Man
      liposomes via mannose receptor-mediated endocytosis.

PMID- 18037188
TI  - Computation of the quasi-independence model for the analysis of triangular
      contingency tables.
AB  - Triangular contingency tables are a special class of incomplete contingency
      tables. Association and independence models are used to analyze such tables. This
      paper presents and compares some methods including the uniform association model
      and the quasi-independence model. These models can be described in terms of the
      association parameters for the analysis of triangular contingency tables having
      ordered categories. A computer program is developed for the analysis of quasi
      independence model for positive (negative) likelihood dependence. The sign test,
      which is a nonparametric test of the independence against the likelihood ratio
      dependence, is also examined. These methods are applied to the disability ratings
      of stroke patients data. Effects of the structural zeros on the results are also
      discussed.

PMID- 18037187
TI  - Expression of hepatitis B virus proteins in transgenic mice alters lipid
      metabolism and induces oxidative stress in the liver.
AB  - BACKGROUND/AIMS: Hepatitis B virus transgenic mice (HBV-Tg mice) have been widely
      used as animal models in the study of pathogenesis and control of hepatitis B. It
      is important for the evaluation of such animal models to define the physiological
      differences between HBV-Tg and wild-type mice. The aim of this research was to
      investigate whether the integrated system biology approach that combines
      proteomics and metabonomics describes the physiological changes and provides new
      insights into the pathogenesis of the early stages of HBV infection. METHODS: In
      this study the protein and metabolite profiles of the liver were established
      based on two-dimensional electrophoresis and HPLC/MS analysis. RESULTS: Several
      protein molecules, whose expression was altered in HBV-Tg mouse liver, were
      identified including protective enzymes against oxidative stress and regulatory
      proteins related to lipid metabolism. Metabonomics confirmed the potential
      derangement of lipid metabolism by discovering the intermediate and the final
      products of lipid metabolism that were markedly changed in transgenic mice.
      CONCLUSIONS: This study demonstrated that HBV antigens could impair host cell
      lipid metabolism and induce modest oxidative stress in vivo.

PMID- 18037189
TI  - A SAS program for calculating cumulative incidence of events (with confidence
      limits) and number at risk at specified time intervals with partially censored
      data.
AB  - Correct analysis and interpretation of longitudinal (cohort) studies with
      partially censored time-to-event data requires that the cumulative count of
      events and censored observations as well as the number at risk be calculated at
      appropriate time points (for example, every year), by baseline group or stratum.
      We present here a simple SAS program, for use in situations in which competing
      risks do not need to be accounted for, that calculates, by baseline group or
      stratum, the cumulative event count, cumulative event probability (with upper and
      lower 95% confidence limits), and number at risk at selected time points that can
      be chosen by the user. We demonstrate the use of the program in the analysis of
      longitudinal time-to-event data from a prospective study, the Atherosclerosis
      Risk In Communities (ARIC) Study, for four groups and a 10-year follow-up. The
      SAS code presented here is easy to follow and modify and can be incorporated
      quickly by the user for immediate use. It provides an especially valuable tool
      for less experienced SAS users.

PMID- 18037190
TI  - Lung cancer mortality in France. Trend analysis and projection between 1975 and
      2012, using a Bayesian age-period-cohort model.
AB  - INTRODUCTION: Lung cancer is currently the most common cancer in the world and as
      such is an important public health concern. One of the main challenges is to
      foresee the evolution of trends in lung cancer mortality rates in order to
      anticipate the future burden of this disease as well as to plan the supply of
      adequate health care. The aim of this study is to propose a quantification of
      future lung cancer mortality rates by gender in France until the year 2012.
      METHODS: Lung cancer mortality data in France (1978-2002) were extracted from the
      National Statistics of Death and analyzed by 5-year age-groups and periods, using
      a Bayesian age-period-cohort model. DISCUSSION: Between 1978 and 2002, female
      lung cancer mortality rate rises by 3.3%year(-1). For men, a slow increase is
      observed until 1988-1992 followed by a declining trend. In 1998-2002, age
      standardized mortality rates were, respectively, 45.5 and 7.6 per 100000 for
      males and for females. By 2008-2012 these figures would reach 40.8 (95%
      credibility interval (CI): 32.7, 50.0) and 12.1 (CI: 11.7, 12.6) per 100000,
      respectively, which represents among women a 4.7% annual increase (CI: 4.5, 5.0).
      RESULTS: Our results highlight the relevance of pursuing public health measures
      in order to cope more actively with tobacco smoking in the prevention strategy
      against lung cancer specifically among women.

PMID- 18037192
TI  - Gut-specific expression of cathepsin L and B in amphioxus Branchiostoma belcheri
      tsingtauense larvae.
AB  - Cathepsin L and B are involved in yolk processing during oocyte maturation and
      embryogenesis in most invertebrates and vertebrates. Here we examine the
      developmental expression of cephalochordate amphioxus cathepsin L (AmphiCL) and
      cathepsin B (AmphiCB) in the adult and developing embryos and larvae. In situ
      hybridization of adult amphioxus demonstrated that both AmphiCL and AmphiCB
      transcripts were strongly expressed in the hepatic caecum and hind-gut besides
      expression at various levels in other tissues examined. Whole mount in situ
      hybridization and RT-PCR techniques revealed that AmphiCL and AmphiCB transcripts
      appeared in the primitive gut in 2-day and 1-day larvae, respectively. However,
      no signals were detected in the early embryos or larvae. Parallel experiments
      were performed measuring AmphiCL and AmphiCB activities in the mature oocytes and
      developing embryos and larvae. Albeit both enzymes were present in the mature
      oocytes, their roles in yolk protein processing remain to be clarified. In
      accordance with gene expression patterns, AmphiCL and AmphiCB activities were
      only detectable in the 2-day larvae, rather than in younger stages, suggesting
      that both AmphiCL and AmphiCB are implicated in the development of gut, and
      inferring no roles for yolk processing during embryogenesis in amphioxus
      Branchiostoma belcheri tsingtauense.

PMID- 18037191
TI  - Promoting effect of 5-azacytidine on the myogenic differentiation of bone marrow
      stromal cells.
AB  - Bone marrow stromal cells (BMSC) can differentiate into various cell types
      including myocytes, which may be valuable in cellular therapy of myocardial
      infarction. In an attempt to increase the myogenic commitment of BMSC, we
      investigated the extent of conversion induced by the demethylation agent 5
      azacytidine. BMSC isolated from the adult rat tibia were exposed in culture to
      5microM 5-azacytidine for 24h, 1 day after seeding. The treatment was repeated at
      weekly intervals and the expression of muscle-specific proteins and genes was
      assessed. The results revealed that cultured cells lost the native expression of
      osteocalcin and alkaline phosphatase as a function of time and began to express
      connexin 43. Exposure to 5-azacytidine of BMSC induced, at 14 days, a myocyte
      resembling phenotype that included the expression of muscle-specific proteins
      (sarcomeric alpha-actin, troponin T, desmin, alpha-actinin, and GATA-4) and genes
      (GATA-4, myoD, desmin, and alpha-actinin), numerous mitochondria and
      myofilaments; however, the latter did not form sarcomeres. Although some of these
      myogenic markers also appeared in untreated cells, exposure to 5-azacytidine
      induced an enhanced response of calcium channels, as well as a threefold increase
      in desmin and myoD gene expression and a twofold increase in alpha-actinin gene
      and protein expression above the control values. In conclusion, the results
      demonstrate a promoting effect of 5-azacytidine on the expression of muscle
      specific proteins and genes in BMSC in culture. Notably, the myogenic
      differentiation takes place over a short period of time. Priming of mesenchymal
      cells to cardiomyogenic differentiation may have significant applications in
      cellular approaches to ameliorate muscle loss after myocardial ischemia.

PMID- 18037193
TI  - 2007 update to the ACC/AHA guidelines for the management of patients with
      unstable angina and non-ST-segment elevation myocardial infarction: implications
      for emergency department practice.
AB  - The American College of Cardiology and American Heart Association have updated
      their guidelines for the management of non-ST-segment-elevation acute coronary
      syndrome for the first time since 2002. In the interim, several important studies
      affecting choices of therapy potentially begun in the emergency department have
      been completed, and care patterns have changed and matured significantly. In this
      review, we present the new recommendations that are pertinent to emergency
      medicine practice and comment on their potential implementation into an evidence
      based, multidisciplinary approach to the evaluation and management of this
      challenging patient population.

PMID- 18037194
TI  - Synthesis, characterization, antioxidant activity and DNA-binding studies of two
      rare earth(III) complexes with naringenin-2-hydroxy benzoyl hydrazone ligand.
AB  - Two novel rare earth complexes, Y(III) complex (1) and Eu(III) complex (2), with
      naringenin-2-hydroxy benzoyl hydrazone ligand were synthesized and characterized.
      The interaction of the two metal complexes and the free ligand with calf thymus
      DNA (CT DNA) was investigated by electronic absorption spectroscopy, fluorescence
      spectroscopy and viscosity measurement. All the experimental evidences indicate
      that these three compounds can strongly bind to CT DNA via an intercalation
      mechanism. The intrinsic binding constants of the Y(III) complex (1), Eu(III)
      complex (2) and the free ligand with CT DNA were 2.1 x 10(4), 8.5 x 10(4) and 1.6
      x 10(4) M(-1), respectively. Furthermore, the antioxidant activity of the metal
      complexes was determined by hydroxyl radical scavenging method in vitro.

PMID- 18037195
TI  - Synthesis and molecular modelling of unsaturated exomethylene pyranonucleoside
      analogues with antitumor and antiviral activities.
AB  - This report describes the total and facile synthesis of the unsaturated keto and
      exomethylene pyranonucleoside analogues, 1-(2,3,4-trideoxy-4-methylene-6-O-trityl
      alpha-D-glycero-hex-2-enopyranosyl)uracil (10), 1-(2,3-dideoxy-alpha-D-glycero
      hex-2-enopyranosyl-4-ulose)uracil (17) and 1-(2,3,4-trideoxy-4-methylene-alpha-D
      glycero-hex-2-enopyranosyl)uracil (18). Commercially available 1,2,3,4,6-penta-O
      acetyl-alpha-D-mannopyranose (1) was condensed with silylated uracil,
      deacetylated and acetalated to afford 1-(2,3-O-isopropylidene-alpha-D
      mannopyranosyl)uracil (4). Two different synthetic routes were investigated for
      the conversion of 4 into the olefinic derivative 1-(2,3,4-trideoxy-4-methylene-6
      O-trityl-alpha-D-glycero-hex-2-enopyranosyl)uracil (10). Although the two
      procedures are quite similar with respect to yields and final products, the
      second also leads to the keto-2',3'-unsaturated analogue (17). The new analogues
      were evaluated for their anticancer and antiviral activities using several tumor
      cell lines and gastrointestinal rotavirus. All of the compounds showed direct
      antiviral effect against rotavirus infectivity in Caco-2 cell line. Moreover, 1
      (2,3,4-trideoxy-4-methylene-6-O-trityl-alpha-D-glycero-hex-2-enopyranosyl)uracil
      (10) was found to be potent in MCF-7 breast carcinoma cell line.

PMID- 18037197
TI  - Windscale and Kyshtym: a double anniversary.
AB  - The autumn of 2007 has seen the fiftieth anniversary of two separate events that
      were of great importance both for the worldwide nuclear industry and for the
      science of radioecology. This short article marks this anniversary by briefly
      reviewing the causes, releases, impacts and legacies of both the Kyshtym accident
      of September 1957 and the Windscale accident of October 1957.

PMID- 18037198
TI  - Trunk and upper extremity kinematics during sitting pivot transfers performed by
      individuals with spinal cord injury.
AB  - BACKGROUND: Although reaching an optimal level of independence during sitting
      pivot transfer is crucial for individuals with spinal cord injury, little is
      known regarding the kinematic requirements of this functional task. METHODS: Ten
      males with spinal cord injury performed independent sitting pivot transfers
      between an initial seat and a target one placed at same (50 cm), lower (40 cm),
      and higher heights (60 cm) than the initial one, using their usual movement
      strategies. Three-dimensional trunk, shoulder, elbow and wrist kinematics were
      collected bilaterally during sitting pivot transfers. Each sitting pivot transfer
      was divided into three phases for analysis: pre-lift, lift-pivot and post-lift.
      Temporal parameters were also documented. FINDINGS: Peak shoulder extension
      displacement and velocities were always higher at the leading shoulder compared
      to the trailing one (P<0.004), and almost coincided with peak trunk velocities
      early during the lift phase. With increasing target seat height, shoulder flexion
      (P<0.011) and elbow extension (P<0.013) displacements and velocities of the
      trailing upper extremity augmented and reached higher values at this upper
      extremity compared to the leading upper extremity, with one exception at the
      shoulder. Elbows generally remained flexed (min=28-56 degrees ) during the lift
      phase of all transfers whereas extreme wrist extension positions (max=84-88
      degrees ) were documented across all transfers. Total durations of transfers (2.6
      2.8s) and lift-pivot phases (1.0-1.3s) were not affected by target seat heights.
      INTERPRETATION: Sitting pivot transfers are characterized by substantial angular
      displacements and velocities at the trunk and upper extremities. Some kinematic
      parameters documented during sitting pivot transfers may increase the risk of
      developing secondary musculoskeletal impairments in this population.

PMID- 18037196
TI  - Chitosan solution enhances the immunoadjuvant properties of GM-CSF.
AB  - Sustained, local delivery of immunomodulatory cytokines is under investigation
      for its ability to enhance vaccine and anti-tumor responses both clinically and
      preclinically. This study evaluates the ability of chitosan, a biocompatible
      polysaccharide, to (1) control the dissemination of a cytokine, GM-CSF, and (2)
      enhance the immunoadjuvant properties of GM-CSF. While cytokines have previously
      been delivered in lipid-based adjuvants and other vehicles, these do not have the
      clinical safety profile or unique properties of chitosan. We found that chitosan
      solution maintained a measurable depot of recombinant GM-CSF (rGM-CSF) at a
      subcutaneous injection site for up to 9 days. In contrast, when delivered in a
      saline vehicle, rGM-CSF was undetectable in 12-24h. Furthermore, a single s.c.
      injection of 20 microg rGM-CSF in chitosan solution (chitosan/rGM-CSF(20 microg))
      transiently expanded lymph nodes up to 4.6-fold and increased the number of MHC
      class II expressing cells and dendritic cells by 7.4-fold and 6.8-fold,
      respectively. These increases were significantly greater than those measured when
      rGM-CSF was administered in saline at the standard preclinical dose and schedule,
      i.e. 4 daily s.c. injections of 20 microg. Furthermore, lymph node cells from
      mice injected with chitosan/rGM-CSF(20 microg) induced greater allogeneic T cell
      proliferation, indicating enhanced antigen presenting capability, than lymph node
      cells from mice injected with rGM-CSF alone. Finally, in vaccination experiments,
      chitosan/rGM-CSF was superior to either chitosan or rGM-CSF alone in enhancing
      the induction of antigen-specific CD4(+) proliferation, peptide-specific CD8(+)
      pentamer staining and cytotoxic T cell lysis. Altogether, chitosan/rGM-CSF
      outperformed standard rGM-CSF administrations in dendritic cell recruitment,
      antigen presentation and vaccine enhancement. We conclude that chitosan solution
      is a promising delivery platform for the sustained, local delivery of rGM-CSF.

PMID- 18037199
TI  - Determination of Hg and diet identification in otter (Lontra longicaudis) feces.
AB  - An analytical procedure for the determination of Hg in otter (Lontra longicaudis)
      feces was developed, to separate fish scales for the identification of the animal
      diet. Samples were washed with ultra-pure water and the suspension was sampled
      and transferred for digestion. The solubilization was performed with nitric
      perchloric acid mixture, and detection carried out by the atomic fluorescence
      spectrometry (AFS). The quality of the analytical procedure was assessed by
      analyzing in-house standard solutions and certified reference materials. Total Hg
      concentrations were in the range of 7.6-156 ng g(-1) (July 2004), 25.6-277 ng g(
      1) (January 2005) and 14.6-744 ng g(-1) (May 2005) that is approximately the same
      order of magnitude for all samples collected in two reservoirs at the Tiete
      River, Brazil. Although Hg concentrations varied with sampling periods and diet,
      high levels were correlated to the percentage of carnivorous fish scales present
      in the otter feces.

PMID- 18037200
TI  - Monitoring aromatic hydrocarbon biodegradation by functional marker genes.
AB  - The development of biological treatment technologies for contaminated
      environments requires tools for obtaining direct information about the
      biodegradation of specific contaminants. The potential of functional gene array
      analysis to monitor changes in the amount of functional marker genes as
      indicators of contaminant biodegradation was investigated. A prototype functional
      gene array was developed for targeting key functions in the biodegradation of
      naphthalene, toluene and xylenes. Internal standard probe based normalization was
      introduced to facilitate comparison across multiple samples. Coupled with one
      colour hybridization, the signal normalization improved the consistency among
      replicate hybridizations resulting in better discrimination for the differences
      in the amount of target DNA. During the naphthalene biodegradation in a PAH
      contaminated soil slurry microcosm, the normalized hybridization signals in
      naphthalene catabolic gene probes were in good agreement with the amount of
      naphthalene-degradation genes and the production of 14CO2. Gene arrays provide
      efficient means for monitoring of contaminant biodegradation in the environment.

PMID- 18037201
TI  - Field monitoring of volatile organic compounds using passive air samplers in an
      industrial city in Japan.
AB  - Highly portable, sensitive, and selective passive air samplers were used to
      investigate ambient volatile organic compound (VOC) levels at multiple sampling
      sites in an industrial city, Fuji, Japan. We determined the spatial distributions
      of 27 species of VOCs in three campaigns: Mar (cold season), May (warm season),
      and Nov (mild season) of 2004. In all campaigns, toluene (geometric mean
      concentration, 14.0microg/m3) was the most abundant VOC, followed by acetaldehyde
      (4.76microg/m3), and formaldehyde (2.58microg/m3). The spatial distributions for
      certain VOCs showed characteristic patterns: high concentrations of benzene and
      formaldehyde were typically found along major roads, whereas high concentrations
      of toluene and tetrachloroethylene (PCE) were usually found near factories. The
      spatial distribution of PCE observed was extremely consistent with the diffusion
      pattern calculated from Pollutant Release and Transfer Register data and
      meteorological data, indicated that passive air samplers are useful for
      determining the sources and distributions of ambient VOCs.

PMID- 18037202
TI  - Perceived social position and health in older adults in Taiwan.
AB  - We examined whether perceived social position predicted mental and physical
      health outcomes (depressive symptoms, cognitive impairment, mobility
      restrictions, and self-assessed health) in a prospective study based on a
      nationally representative sample of older persons in Taiwan. Cross-sectional and
      longitudinal models were used to demonstrate the relationship between perceived
      social position and health, as reported by participants in the Social Environment
      and Biomarkers of Aging Study in Taiwan (SEBAS). Lower perceived social position
      predicted declining health beyond what was accounted for by objective indicators
      of socioeconomic position. As predicted, the effect was substantially reduced for
      all health outcomes in the presence of controls for baseline health. After
      including these controls, perceived social position was significantly related
      only to depressive symptoms. The findings suggest that the strength of the
      association between perceived social position and health may have been overstated
      in cross-sectional studies.

PMID- 18037204
TI  - Understanding the role of cancer worry in creating a "teachable moment" for
      multiple risk factor reduction.
AB  - The manuscript examines the influence of contextual factors on whether and for
      whom a colon polyp diagnosis might be a teachable moment, as indicated by
      engagement with a proactively delivered intervention. Baseline and 8-month follow
      up data were analyzed from a two-site behavioral intervention trial with patients
      in Massachusetts and North Carolina, USA who had recently undergone polypectomy
      for pre-cancerous colon polyps and were randomized to a behavior change
      intervention condition (N=591). Intervention "buy-in" was used as an indicator of
      response consistent with the polyp identification serving as a teachable moment.
      Cancer worry, personal risk, health-related self-identity and other
      sociodemographic factors were tested to predict intervention buy-in. As
      predicted, those who were most worried about colon cancer were most likely to
      engage in the intervention. One indicator of personal risk, number of risk
      behaviors, was significantly and negatively associated with buy-in. Predictors of
      intervention buy-in and cancer worry were not consistent. We recommend that
      expanded measures of affect and health-related self-identity should be considered
      in future research to understand the motivational potential of health events for
      increasing engagement in effective behavior change interventions.

PMID- 18037205
TI  - Fragrance material review on alpha-amylcinnamyl alcohol.
AB  - A toxicologic and dermatologic review of alpha-amylcinnamyl alcohol when used as
      a fragrance ingredient is presented.

PMID- 18037206
TI  - Fragrance material review on cinnamyl isovalerate.
AB  - A toxicologic and dermatologic review of cinnamyl isovalerate when used as a
      fragrance ingredient is presented.

PMID- 18037207
TI  - Fragrance material review on allyl cinnamate.
AB  - A toxicologic and dermatologic review of allyl cinnamate when used as a fragrance
      ingredient is presented.

PMID- 18037208
TI  - Fragrance material review on pentyl cinnamate.
AB  - A toxicologic and dermatologic review of pentyl cinnamate when used as a
      fragrance ingredient is presented.

PMID- 18037209
TI  - Fragrance material review on cinnamyl formate.
AB  - A toxicologic and dermatologic review of cinnamyl formate when used as a
      fragrance ingredient is presented.

PMID- 18037210
TI  - Fragrance material review on alpha-iso-methylionone.
AB  - A toxicologic and dermatologic review of alpha-iso-methylionone when used as a
      fragrance ingredient is presented.

PMID- 18037211
TI  - Fragrance material review on methyl cinnamate.
AB  - A toxicologic and dermatologic review of methyl cinnamate when used as a
      fragrance ingredient is presented.

PMID- 18037212
TI  - Fragrance material review on alpha-ionone.
AB  - A toxicologic and dermatologic review of alpha-ionone when used as a fragrance
      ingredient is presented.

PMID- 18037213
TI  - Fragrance material review on cis-beta-damascone.
AB  - A toxicologic and dermatologic review of cis-beta-damascone when used as a
      fragrance ingredient is presented.

PMID- 18037214
TI  - Fragrance material review on benzyl cinnamate.
AB  - A toxicologic and dermatologic review of benzyl cinnamate when used as a
      fragrance ingredient is presented.

PMID- 18037215
TI  - Fragrance material review on cinnamyl cinnamate.
AB  - A toxicologic and dermatologic review of Cinnamyl cinnamate when used as a
      fragrance ingredient is presented.

PMID- 18037216
TI  - Fragrance material review on ethyl cinnamate.
AB  - A toxicologic and dermatologic review of ethyl cinnamate when used as a fragrance
      ingredient is presented.

PMID- 18037217
TI  - Fragrance material review on cinnamyl propionate.
AB  - A toxicologic and dermatologic review of cinnamyl propionate when used as a
      fragrance ingredient is presented.

PMID- 18037218
TI  - Fragrance material review on cinnamyl butyrate.
AB  - A toxicologic and dermatologic review of cinnamyl butyrate when used as a
      fragrance ingredient is presented.

PMID- 18037219
TI  - Fragrance material review on butyl cinnamate.
AB  - A toxicologic and dermatologic review of butyl cinnamate when used as a fragrance
      ingredient is presented.

PMID- 18037220
TI  - [Coverage of dorsal distal skin defects of the digits. Techniques and
      indications].
AB  - Distal dorsal skin defects of the digits could be considered as a surgical
      entity. The coverage of this area is challenging according to the following
      points: the proximity of the distal interphalangeal joint, the thinness of the
      extensor apparatus and the vicinity of the nail. Among the numerous flaps
      described, the homodigital turnover pedicled flaps appear the most effective
      option rather than cross-finger flaps.

PMID- 18037221
TI  - A cell-permeable peptide inhibitor TAT-JBD reduces the MPP+-induced caspase-9
      activation but does not prevent the dopaminergic degeneration in substantia nigra
      of rats.
AB  - Many studies showed that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      which was widely used to produce Parkinson's disease (PD)-like models in animals
      can elicit apoptosis with increase of caspase activity via its neurotoxic
      metabolite 1-methyl-4-phenylpyridinium ion (MPP(+)). Another pathway shown in
      MPTP-mediated nigrostriatal dopaminergic cell death involved the c-Jun-N-terminal
      kinases (JNKs) which are stress-activated protein kinases (SAPKs). Activation of
      the JNKs leads to the activation of transcription factors such as c-Jun that
      regulates its own expression. However, it is not known whether the activation of
      c-Jun is crucial in the stimulation of caspases leading to apoptosis observed in
      PD-like models. The aim of this study was to investigate the cellular expression
      and phosphorylation of c-Jun and the caspase-9 activity in rat injured with an
      intranigral injection of MPP(+). Furthermore, we determined the effects of a cell
      permeable peptide TAT-JBD, inhibiting selectively JNKs, on apoptosis markers and
      on the expression of tyrosine hydroxylase (TH). Our results showed that MPP(+)
      induced not only an activation of c-Jun but also an early and robust stimulation
      of caspase-9 in midbrain of rats. Furthermore, a preliminary intravenous
      injection of TAT-JBD reduced the caspase-9 activation specifically induced by
      MPP(+) suggesting a control of the JNKs pathway on the intrinsic way of apoptosis
      in MPP(+)-toxicity. However, the inhibition of the JNK pathway did not prevent TH
      inhibition, DNA fragmentation and Bad expression in MPP(+)-lesioned substantia
      nigra of rats. Therefore, the possibility of intervention on the JNK pathway as a
      therapeutic strategy in Parkinson's disease is questionable.

PMID- 18037222
TI  - Magnesium in cardiopulmonary resuscitation: critical review.
AB  - Although many different drugs and interventions have been studied in cardiac
      arrest to improve survival rates and neurological outcome, the results are still
      very poor. Magnesium (Mg) has important electrophysiological effects and normal
      concentrations are required to maintain regular cardiac conduction, rhythm and
      vascular tone, but its role in improving survival rates and neurological outcome
      in victims of cardiac arrest is not completely understood. We conducted a
      systematic review to identify evidence regarding the role of Mg in cardiac
      arrest. Specifically, we looked for data to answer if survival rates and
      neurological outcome are related to the administration of Mg either during CPR or
      following return of spontaneous circulation. We found that there are very few
      data available about the role of Mg in the treatment of cardiac arrest. Although
      two non-randomised and one animal study reported promising results, the lack of
      high quality studies makes it impossible to recommend for or against the
      administration of Mg during or early after resuscitation to improve outcome.

PMID- 18037223
TI  - Early high-dose erythropoietin therapy and hypothermia after out-of-hospital
      cardiac arrest: a matched control study.
AB  - AIM: To test the possible neuroprotective effect of early high-dose
      erythropoietin-alpha (Epo-alpha) after out-of-hospital cardiac arrest (OHCA).
      METHODS: A matched control study. Following resuscitation with mild hypothermia
      after OHCA, participants received a first dose of Epo-alpha followed by four
      additional injections within 48 h (40,000 IU intravenously each injection).
      Plasma Epo-alpha levels were measured at different time points. Outcome and
      adverse events were assessed up to day 28 and were compared with those of matched
      paired controls. RESULTS: In all 18 participants received Epo-alpha and were
      compared with 40 matched controls. Pharmacokinetic variables were similar to
      those previously reported for healthy people or for persons treated with usual
      dosages of Epo. At day 28, survival rates among the Epo-treated group and the
      controls (55% versus 47.5%, p=0.17) and rates of full neurological recovery (55%
      versus 37.5%) did not differ significantly. Incidences of thrombocytosis in the
      Epo-treated group and controls were 15% and 5%, respectively; an arterial
      vascular thrombosis was observed in one case (5%) from the Epo-treated cohort.
      CONCLUSIONS: Among victims of OHCA treated with Epo-alpha and hypothermia, we
      observed a high survival rate, with no minor cerebral sequels but potential
      haematological side effects. Future studies of Epo should pay particular
      attention to these findings.

PMID- 18037224
TI  - Accidental shock to rescuer during successful defibrillation of ventricular
      fibrillation--a case of human involuntary automaticity.

PMID- 18037225
TI  - Disease-modifying drugs and Parkinson's disease.
AB  - Symptomatic medications, l-Dopa and dopaminergic agents, remain the only
      clinically pertinent pharmacological treatment proven effective and available for
      the large population of patients with Parkinson's disease. The challenge for the
      pharmaceutical industry is to develop disease-modifying drugs which could arrest,
      delay or at least oppose the progression of the specific pathogenic processes
      underlying Parkinson's disease. The purpose of this review, based on recent
      biological and genetic data to be validated with appropriate animal models, was
      to re-examine the putative neuroprotective agents in Parkinson's disease and
      discuss the development of new strategies with the ultimate goal of demonstrating
      neurocytoprotective activity in this neurodegenerative disease. Since guidelines
      for research on neurocytoprotective drugs remain to be written, innovation will
      be the key to success of future clinical trials. It is reasonable to expect that
      future advances in our understanding of the pathogenic processes of Parkinson's
      disease will open the way to new perspectives for the treatment of other
      neurodegenerative diseases.

PMID- 18037226
TI  - Mutated D4-guanine diphosphate-dissociation inhibitor is found in human leukemic
      cells and promotes leukemic cell invasion.
AB  - OBJECTIVE: Rho GTPase may be involved in human cancer invasion via the
      augmentation of cell motility and adhesion. We report on two point mutations of
      the D4-guanine diphosphate (GDP)-dissociation inhibitor (GDI) gene, one of the
      Rho-GDIs, which were found in a human leukemic cell line, Reh, and the mutated D4
      GDI functions as an accelerator of leukemic cell invasion. MATERIAL AND METHODS:
      We investigated the altered activity of GDP dissociation by mutated (mt) D4-GDI
      and the functions of this mt and wild-type (wt) D4-GDI in invasion. The mice
      inoculated with wt or mt D4-GDI vector-transfected Raji cells were observed and
      examined pathologically. Adhesiveness and cell motility of wt or mt D4-GDI vector
      transfected Raji cells were examined. Finally, it was examined whether Rho
      activation was changed by mutation of D4-GDI under the condition of Rho-GDI
      knockdown. RESULTS: Two point mutations of the D4-GDI gene were found in Reh
      cells. The region of mutations is conserved among members of the Rho-GDI family
      at the amino acid level. D4-GDI with two mutations (V68L and V69A) functioned in
      a dominant negative manner in the inhibition of GDP dissociation from Rho. Severe
      combined immune-deficient mice inoculated with Raji cells developed
      hemiparalysis. The Raji cells were present in bone marrow and peripheral blood,
      and hepatic invasion was observed in 20% of the mice. Mice inoculated with wt D4
      GDI vector-transfected Raji cells (wt D4) showed later paralysis and none
      developed hepatic invasion. Mice inoculated with mt D4-GDI-transfected Raji cells
      (mt D4) showed a 5-day reduction in the time to paraplegia and death. In
      addition, hepatic invasion was evident in 80% of mice transplanted with mt D4
      cells. There were no differences in growth rates and amounts of guanine
      triphosphate (GTP)-bound Rho, cdc42, or Rac among all clones, however, GTP-bound
      Rho in mt D4 clone with short hairpin RNA (shRNA) vector for Rho-GDI knockdown
      was increased compared with wt D4 clone with shRNA vector for Rho-GDI knockdown.
      The mt D4 cells showed an augmentation of adhesiveness and cell motility. On the
      other hand, wt D4 cells showed a decreased ability of cell motility. CONCLUSION:
      These results suggest the mutated D4-GDI functions as a dominant negative
      molecule against the wt D4-GDI and accelerates invasion via regulation of
      cytoskeletal machinery.

PMID- 18037228
TI  - Sickness and survival in bladder cancer: is comorbidity the crystal ball?

PMID- 18037227
TI  - A novel mechanism of erythrocyte capture from circulation in humans.
AB  - OBJECTIVE: The capture of blood cells from the circulation is mediated by highly
      specialized adhesion molecules. These molecules contribute to the specificity of
      recruitment for various subsets. Here, we used a simple substrate of hyaluronic
      acid to investigate the specificity of CD44-mediated recruitment from human whole
      blood under shear conditions. MATERIALS AND METHODS: Human whole blood was
      perfused through a parallel-plate flow chamber, which mimics intravascular
      conditions. Microscopy was used to directly observe blood-cell interactions with
      adhesion molecule substrates. RESULTS: Erythrocytes, but not leukocytes,
      efficiently tethered to and rolled on the hyaluronic acid substrate. These
      interactions were demonstrated to be mediated by CD44 and regulated by the sialic
      acid content of the cells. Inflammatory stimuli did not result in enhanced
      erythrocyte rolling. Rather, interactions were restricted to aged erythrocytes
      approaching senescence. This mechanism of erythrocyte capture from the blood flow
      was found to be restricted to primates and not conserved across mammalian
      species. CONCLUSION: This is the first report of erythrocyte tethering and
      rolling under shear conditions, a behavior, until now, thought to be exclusive to
      leukocytes. It may represent an important mechanism to identify, capture, and
      clear old erythrocytes during normal homeostasis or clot formation.

PMID- 18037230
TI  - Expression of the full-length telomerase reverse transcriptase (hTERT) transcript
      in both malignant and normal gastric tissues.
AB  - Activation of telomerase by the induction of a full-length telomerase reverse
      transcriptase (hTERT) transcript is a critical step during cellular
      immortalization and malignant transformation. Telomerase activity or hTERT
      expression has thus served as diagnostic and/or prognostic markers in different
      types of human malignancies. In the present study, we investigated the expression
      of the telomerase components hTERT and telomerase RNA template (hTER) in normal
      and malignant gastric tissues derived from 37 patients with gastric cancers.
      Overall hTERT mRNA was detectable in 33/37 (90%) of tumour specimens and 23/37
      (62%) of the corresponding normal gastric tissues. Twenty-five of thirty-seven
      tumours (71%) expressed the full-length hTERT mRNA, and unexpectedly, this full
      length transcript was found in 16 of 37 (43%) normal gastric tissues.
      Immunohistochemical analyses demonstrated a positive hTERT staining in small
      fractions of normal epithelial cells and in most gastric cancer cells. A close
      correlation between the presence of a full-length hTERT transcript and the c-MYC
      oncogene expression was observed in both normal and cancerous gastric specimens.
      Moreover, the full-length hTERT expression was positively associated with the
      tumour size in these patients. Similar levels of hTER expression were expressed
      in tumour and their corresponding normal tissues. The finding that the full
      length hTERT transcript was present in both normal and malignant gastric tissues
      will preclude its use as a gastric cancer marker. Nevertheless, full-length hTERT
      mRNA expression may indicate a progressive gastric cancer, and its presence in
      normal gastric mucosa may have an impact on the anti-telomerase strategy for
      cancer therapeutic purpose.

PMID- 18037229
TI  - sHA 14-1, a stable and ROS-free antagonist against anti-apoptotic Bcl-2 proteins,
      bypasses drug resistances and synergizes cancer therapies in human leukemia cell.
AB  - HA 14-1, a small-molecule antagonist against anti-apoptotic Bcl-2 proteins, was
      demonstrated to induce selective cytotoxicity toward malignant cells and to
      overcome drug resistance. Due to its poor stability and the reactive oxygen
      species (ROS) generated by its decomposition, chemical modification of HA 14-1 is
      needed for its future development. We have synthesized a stabilized analog of HA
      14-1--sHA 14-1, which did not induce the formation of ROS. As expected from a
      putative antagonist against anti-apoptotic Bcl-2 proteins like HA 14-1, sHA 14-1
      disrupted the binding interaction of a Bak BH3 peptide with Bcl-2 or Bcl-X(L)
      protein, inhibited the growth of tumor cells through the induction of apoptosis,
      and circumvented the drug resistance induced by the over-expression of anti
      apoptotic Bcl-2 and Bcl-X(L) proteins. Interestingly, the impairment of extrinsic
      apoptotic pathway induced moderate resistance to sHA 14-1. The moderate
      resistance suggested that sHA 14-1 generated part of its apoptotic stress through
      the intrinsic pathway, possibly through its antagonism against anti-apoptotic Bcl
      2 proteins. The resistance indicated that sHA 14-1 generated apoptotic stress
      through the extrinsic apoptotic pathway as well. The ability of sHA 14-1 to
      induce apoptotic stress through both pathways was further supported by the
      synergism of sHA 14-1 towards the cytotoxicities of Fas ligand and dexamethasone
      in Jurkat cells. Taken together, these findings suggest that sHA 14-1 may
      represent a promising candidate for the treatment of drug-resistant cancers
      either as a monotherapy or in combination with current cancer therapies.

PMID- 18037231
TI  - Repair of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA
      pyridyloxobutylation by nucleotide excision repair.
AB  - The tobacco-specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) forms DNA methylating and pyridyloxobutylating species. In this
      study, the involvement of nucleotide excision repair (NER) in the repair of
      pyridyloxobutyl adducts was assessed using an in vitro NER assay with
      pyridyloxobutylated plasmid DNA. Nuclear extracts from NER-deficient xeroderma
      pigmentosum (XP) cells, XPA and XPC, were less active at repairing
      pyridyloxobutyl adducts than were extracts from normal cells, while combining NER
      deficient extracts reconstituted activity. Also, NER-deficient cells were more
      susceptible to NNKOAc-induced cytotoxicity than were normal cells. Results
      demonstrate a role for NER in the repair of NNK-induced pyridyloxobutylation.

PMID- 18037232
TI  - The 3' UTR IGF2R-A2/B2 variant is associated with increased tumor growth and
      advanced stages in non-small cell lung cancer.
AB  - Normal function of insulin-like growth factor II receptor (IGF2R) gene has been
      associated with negative control of tumor growth in vivo and in vitro. Rare
      alleles at a 3' UTR short tandem repeat polymorphism of IGF2R are known to
      decrease transcript stability. One such allele (A2/B2) increases significantly
      the risk of oral squamous cell carcinoma and non-small cell lung carcinoma
      (NSCLC) in Caucasians. To determine potential association(s) between A2/B2
      presence and development and/or progression of disease, we examined in 103 NSCLC
      patients, free of IGF2R allelic imbalance aberrations, the 3' UTR allelic status
      in relation to tumor kinetic parameters (proliferation index-PI and apoptotic
      index-AI) and clinicopathological data. PCR and automated sequence analyses were
      employed to genotype the IGF2R 3' UTR polymorphism. Given that, oncogenic
      mitogens, which escape degradation by IGF2R, can also activate p53 through a DNA
      damage response, the patterns between p53 status and IGF2R genetic constitution
      were also evaluated in relation to the above parameters. The A2/B2 variant was
      significantly more common (p=0.005, chi2-test) in lung cancer patients (25% vs
      15%). Its presence was accompanied by high cellular proliferation (p=0.028, t
      test) along with increased tumor cell growth (GI=PI/AI) (p=0.022, t-test) and it
      was significantly found in advanced stages. Also, patients carrying the A2/B2 in
      their genetic constitution that exhibit aberrant p53 expression have faster
      growing tumors and progress more rapidly to advanced stages. In conclusion, the
      IGF2R-A2/B2 variant probably provides a selective advantage for NSCLC progression
      through increased tumor growth.

PMID- 18037233
TI  - Bioassay of methyl tertiary-butyl ether (MTBE) toxicity on rainbow trout fish.
AB  - Methyl tertiary-butyl ether (MTBE) has been widely used as a gasoline additive.
      Water resource contamination due to spillage and accidental leakage of gasoline
      during fuel transportation may cause an important threat to aquatic life. In this
      work, the bioassay of MTBE toxicity on rainbow trout was performed. MTBE
      solutions of 250, 500, 750, 1000, and 1250 mg L(-1) were prepared in five
      aquariums and aerated for 96 h. LC50 values of each experiment were measured
      according to probit analysis. A mathematical relationship between time exposure
      and LC50 of MTBE for rainbow trout was developed. The relative toxicity of MTBE
      to rainbow trout and to other organisms was also reviewed. It was shown that the
      toxicity of MTBE does not change significantly in the time exposure between 24
      and 72 h varying from 878 to 831 mg L(-1), respectively. After 72 h of rainbow
      trout exposure to MTBE, LC50 value gradually decreased and reached 773 mg L(-1)
      in 96 h of contact time. In conclusion, the result of this work showed that the
      toxicity of MTBE to rainbow trout was relatively low.

PMID- 18037234
TI  - Critical rotational speed model of the rotating roll electrode in corona
      electrostatic separation for recycling waste printed circuit boards.
AB  - Waste printed circuit board (PCB) is increasing worldwide. The corona
      electrostatic separation (CES) was an effective and environmental protection way
      to recycle resource from waste PCBs. The aim of this paper is to analyze the main
      factor (rotational speed) that affects the efficiency of CES from the point of
      view of electrostatics and mechanics. A quantitative method for analyzing the
      affection of rotational speed was studied and the model for separating flat
      nonmetal particles in waste PCBs was established. The conception of "charging
      critical rotational speed" and "detaching critical rotational speed" were
      presented. Experiments with the waste PCBs verified the theoretical model, and
      the experimental results were in good agreement with the theoretical model. The
      results indicated that the purity and recycle percentage of materials got a good
      level when the rotational speed was about 70 rpm and the critical rotational
      speed of small particles was higher than big particles. The model can guide the
      definition of operator parameter and the design of CES, which are needed for the
      development of any new application of the electrostatic separation method.

PMID- 18037235
TI  - Distribution of phthalic acid esters in Wuhan section of the Yangtze River,
      China.
AB  - Samples of water and sediment were collected in Wuhan section of the Yangtze
      River in high and low water periods. Concentrations, distribution and transitions
      of Phthalic Acid Esters (PAEs) between water and sediment phases in Wuhan section
      were assessed. Results demonstrated that di-n-butyl phthalate (DBP) and di-(2
      ethylhexyl) phthalate (DEHP) were the main pollutants among five studied PAEs,
      exceeding the Surface Water Quality Criteria of China in 82.4% of the studied
      water samples. For water phase, PAE concentrations in the main stream were 0.034
      0.456 and 35.73-91.22 microg/L in high and low water periods, respectively; for
      sediment phase, PAE concentrations in the main stream were 151.7-450.0 and 76.3
      275.9 microg/g in high and low water periods, respectively. The calculated Koc
      (organic carbon content normalized sorption coefficients) values in each sampling
      site indicated that DBP and DEHP had similar potentials to transfer between water
      and sediment phases in two samplings. PAEs in water and sediment phases of Wuhan
      section were similar to Velino River of Italy and the middle and lower Yellow
      River of China in comparison with kinds of water bodies all around the world.

PMID- 18037236
TI  - A method for decomposition of hexachlorobenzene by gamma-alumina.
AB  - A method of decomposing hexachlorobenzene (HCB) by gamma-alumina was investigated
      at low temperature of 300 degrees C. It was found that HCB was rather quickly
      decomposed under such a condition. Decomposition efficiency (DE) increases with
      increasing the surface area of gamma-alumina. Pretreated gamma-alumina has a
      better performance for the decomposition reaction. A high decomposition
      efficiency within the short reactive time of 60 min was achieved to be 94.2%,
      which was obtained by preheating gamma-alumina with the surface area of 220
      m(2)g(-1) at 450 degrees C for 2 h. High surface area and appropriate
      pretreatment temperature probably provide more reactive sites such as the
      isolated OH groups and Al(3+) sites surrounded by O(2-) sites. These sites may
      induce the decomposition of HCB via a main ring-cracking process. The present
      study, hopefully, holds the promise for the eliminating of HCB contained
      hazardous materials in industrial application.

PMID- 18037237
TI  - Mineral phases of weathered and recent electric arc furnace dust.
AB  - A weathered and a recent sample of electric arc furnace dust (EAFD), generated in
      a southern Brazilian steel industry, were characterized by X-ray fluorescence
      spectroscopy (XFA), powder X-ray diffraction (XRD), thermogravimetric analysis
      (TG), scanning electron microscopy (SEM) with energy dispersive spectroscopy
      (EDS) probe and Fourier transform infrared spectroscopy (FTIR). A quantitative
      phase composition model, that accounts for the observed data and for the physico
      chemical conditions of formation, was postulated for each material. One sample,
      in the form of a wet paste, was collected from the lowest part of a landfill and
      corresponds to a weathered material whereas the other sample was collected from
      the top portion of the landfill and corresponds to a recently produced material.
      The dominant cations present in both samples are iron, zinc and lead with minor
      amounts of manganese, calcium and silicon. The dominant mineralogical phases
      identified in both materials are Magnetite, Franklinite and Zincite. The recent
      sample has Laurionite whereas the weathered sample has Hydrocerussite and
      Hydrozincite.

PMID- 18037238
TI  - Biodegradation dynamics of high catechol concentrations by Aspergillus awamori.
AB  - The biodegradation process of high catechol concentrations by Aspergillus awamori
      was investigated. The values of the kinetic constants for a model of specific
      growth rate at different initial conditions were determined. At 1.0 g/L catechol
      concentration, the biodegradation process proceeded in the conditions of
      substrate limitation. At higher catechol concentrations (2.0 and 3.0 g/L) a
      presence of substrate inhibition was established. The dynamics of the specific
      catechol degradation rate was studied and the values of catechol and biomass
      concentrations, maximizing the specific catechol degradation rate, were estimated
      analytically. The specified ratio catechol/biomass could serve as a starting base
      for determination of the initial conditions for a batch process, for specifying
      the moment of feeding for a fed-batch process, and for monitoring and control of
      a continuous process by the aim of time-optimal control.

PMID- 18037239
TI  - Application of flat-sheet membrane to thickening and digestion of waste activated
      sludge (WAS).
AB  - The feasibility of using flat-sheet membrane for waste activated sludge (WAS)
      thickening and digestion was studied in this paper. The characteristics of the
      processes including the thickening efficiency, effluent water quality and
      filtration properties of the membrane for sludge thickening process (MST),
      digestion efficiency, effluent water quality and membrane permeability of the
      membrane for sludge simultaneous thickening and digestion process (MSTD) were
      investigated. Test results showed that good sludge thickening efficiency and
      superior effluent water quality were obtained in the MST process under hydraulic
      retention time (HRT) 0.26 and 2 d operation of each cycle, and the membrane
      fouling was mainly due to the increase of apparent viscosity of mixed liquors and
      the decrease of the cross-flow velocity (CFV) along membrane surfaces during one
      thickening cycle. Membranes were also selected for the processes and M1 membrane
      of polyvinylidene fluoride (PVDF) material with pore size 0.2 microm demonstrated
      better permeability compared with other three membranes. About 80% MLSS
      destruction rate and 73% MLVSS destruction rate were achieved under HRT 1 d,
      dissolved oxygen (DO) concentration 0.5-1.5 mg/L, temperature 20-28 degrees C and
      15 d operation for one cycle in MSTD process, and membrane fouling of MSTD
      process was attributed to not only the reason of MST process mentioned above, but
      also the change of sludge properties such as the increase of soluble COD and
      microbial polymeric substances including EPS, carbohydrate and nucleic acids,
      etc. of the mixed liquors.

PMID- 18037240
TI  - Regeneration of granular activated carbon saturated with acetone and isopropyl
      alcohol via a recirculation process under H2O2/UV oxidation.
AB  - This study examines a water-based system, coupling an adsorber and a
      photoreactor, for regeneration of granular activated carbon (GAC) saturated with
      acetone and isopropyl alcohol (IPA). Through water recirculation the regeneration
      reaction was operated in both intermittent and continuous ultraviolet
      illumination modes. With a periodic dosage of hydrogen peroxide not only was
      regeneration efficient but it was also catalyzed by GAC in the adsorber. The
      concentrations of acetone, solution chemical oxygen demand (COD), pH and organic
      residues on GAC surfaces were measured during regenerations. Both pH and solution
      COD were found to correlate with regeneration completion as measured by organic
      residue on GAC surfaces in four regeneration cycles with acetone. Solution pH
      decreased to the acidic values and then returned to near its original value when
      organic residues were 0.085-0.255 mg/g GAC, that is, destruction efficiency of
      adsorbed acetone on the GAC surface was more than 99%. Likewise, solution COD
      became low (<100 mg/l) at regeneration completion. The pH variation pattern was
      then applied to another four cycles of regeneration with IPA, and successfully
      reflected the timing of complete regeneration. The final levels of organic
      residue on GAC surfaces were between 0.135 and 0.310 mg/g GAC in each of four
      regeneration cycles, each of which had been stopped based on the measurements of
      pH and solution COD. Furthermore, nearly the same batch of GAC could be
      repeatedly used with little changes in physicochemical properties in each of
      eight cycles: adsorptive capacities were 95+/-7 mg acetone/g GAC and 87+/-3 mg
      IPA/g GAC, and breakthrough time was 0.86+/-0.05 for acetone and 0.78+/-0.03 h
      for IPA. An economic assessment of the system showed that the operating cost was
      about 0.04 USD for treating every gram of acetone in the air.

PMID- 18037241
TI  - Effects of arterial and cardiopulmonary baroreceptor activation on the upper limb
      nociceptive flexion reflex and electrocutaneous pain in humans.
AB  - Attenuation of the lower limb nociceptive flexion reflex (NFR) during the cardiac
      cycle has been attributed to inhibition of sensorimotor function by arterial
      baroreceptor activation. It has been proposed that cardiopulmonary baroreceptors
      might have similar inhibitory effects. This study examined the effects of
      arterial and cardiopulmonary baroreceptor stimulation on nociceptive responding
      in the upper limb by delivering electrocutaneous stimuli to the ulnar nerve at 0,
      150, 300, 450, or 600 ms after the R-wave of the electrocardiogram while
      participants lay supine with their legs raised or lowered. Nociceptive responding
      varied in a quadratic manner with phase of the cardiac cycle; responses were
      lowest at R+450 ms. Nociceptive responding and pain ratings did not differ
      between postures suggesting no cardiopulmonary effects. This phasic modulation of
      the upper limb withdrawal response provides further support for arterial
      baroreceptor-mediated inhibition of nociceptive transmission.

PMID- 18037242
TI  - Tetrodotoxin inhibits the development and expression of neuropathic pain induced
      by paclitaxel in mice.
AB  - We evaluated the effect of low doses of systemically administered tetrodotoxin
      (TTX) on the development and expression of neuropathic pain induced by paclitaxel
      in mice. Treatment with paclitaxel (2mg/kg, i.p., once daily during 5 days)
      produced long-lasting (2-4 weeks) heat hyperalgesia (plantar test), mechanical
      allodynia (electronic Von Frey test) and cold allodynia (acetone drop method),
      with maximum effects observed on days 7, 10 and 10-14, respectively. Acute
      subcutaneous treatment with 1 or 3 microg/kg of TTX reduced the expression of
      mechanical allodynia, whereas higher doses (3 or 6 microg/kg) were required to
      reduce the expression of cold allodynia and heat hyperalgesia. In contrast, TTX
      (3 or 6 microg/kg, s.c.) did not affect the response to the same thermal and
      mechanical stimuli in control animals, which indicates that the antihyperalgesic
      and antiallodynic effects of TTX were not due to unspecific inhibition of the
      perception of these stimuli. Administration of TTX (6 microg/kg, s.c.) 30 min
      before each of the 5 doses of paclitaxel did not modify the development of heat
      hyperalgesia produced by the antineoplastic, but abolished the development of
      mechanical and cold allodynia. Coadministration of a lower dose of TTX (3
      microg/kg) also prevented the development of mechanical allodynia. No signs of
      TTX-induced toxicity or motor incoordination were observed. These data suggest
      that low doses of TTX can be useful to prevent and treat paclitaxel-induced
      neuropathic pain, and that TTX-sensitive subtypes of sodium channels play a role
      in the pathogenesis of chemotherapy-induced neuropathic pain.

PMID- 18037243
TI  - Hypnosis and the analgesic effect of suggestions.

PMID- 18037244
TI  - The use of age-clustered pooled faecal samples for monitoring worm control in
      horses.
AB  - A study was performed on two horse farms to evaluate the use of age-clustered
      pooled faecal samples for monitoring worm control in horses. In total 109 horses,
      57 on farm A and 52 on farm B, were monitored at weekly intervals between 6 and
      14 weeks after ivermectin treatment. This was performed through pooled faecal
      samples of pools of up to 10 horses of the groups 'yearlings' (both farms), '2
      year-old' (two pools in farm A), '3-year-old' (farm A) and adult horses (four
      pools on farm A and five pools on farm B), which were compared with the mean
      individual faecal egg counts of the same pools. A very high correlation between
      the faecal egg counts in pooled samples and the mean faecal egg counts was seen
      and also between the faecal egg counts in pooled samples and larval counts from
      pooled faecal larval cultures. Faecal egg counts increased more rapidly in
      yearlings and 2-year-old horses than in older horses. This implied that in these
      groups of young animals faecal egg counts of more than 200 EPG were reached at or
      just after the egg reappearance period (ERP) of 8 weeks that is usually indicated
      for ivermectin. This probably means that, certainly under intensive conditions,
      repeated treatment at this ERP is warranted in these young animals, with or
      without monitoring through faecal examination. A different situation is seen in
      adult animals. Based on the mean faecal egg counts on both farms and on the
      results of pooled samples in farm A, using 100 EPG as threshold, no justification
      for treatment was seen throughout the experimental period. However, on farm B
      values of 100 EPG were seen at 9 and 11, 13 and 14 and 14 weeks after ivermectin
      treatment in pools 10, 12 and 13, respectively. This coincided with the presence
      of one or two horses with egg counts above 200 EPG. The conclusion is that random
      pooled faecal samples of 10 adult horses from a larger herd, starting at the ERP
      and repeating it at, for instance, 4-week intervals, could be used for decisions
      on worm control. However, there would be a certain risk for underestimating
      pasture contamination through missing high-egg excreters. An alternative use of
      pooled samples would be as a cheap first screening to detect which adult horses
      really contribute to pasture contamination with worm eggs on a farm. All horses
      should be sampled and subsequently animals from 'positive' pools can be
      reexamined individually.

PMID- 18037246
TI  - Glutamate transporter blockade affects Ca(2+) responses in astrocytes.
AB  - Brief pretreatment of astrocytes in culture with glutamate (500 microM for 20
      min), was earlier shown to significantly enhance the Ca(2+) responses to a
      depolarizing pulse. It is known that malfunction of glutamate transporters
      increases extracellular glutamate concentration. We hypothesized that
      pretreatment of astrocytes with glutamate in conditions where the glutamate
      transporter activity is blocked should cause further elevation of the Ca(2+)
      responses to a depolarizing pulse. To test the hypothesis we pretreated
      astrocytes in culture (primary rat astrocyte cultures) with glutamate (500
      microM) and glutamate transport inhibitor, threo-beta-hydroxy-aspartate (200
      microM, TBHA) or glutamate (500 microM) in Na(+) free extracellular solution for
      20 min. The Ca(2+) responses were elicited by depolarization of the astrocyte to
      evoke voltage-gated Ca(2+) currents. Paradoxical attenuation of the Ca(2+)
      transients was observed when the glutamate pretreatment was done in conditions
      that blocked glutamate transport, accompanied by faster rise and decay times.
      When the experiments were done on astrocyte pairs that were pretreated with
      glutamate and TBHA, we observed attenuated Ca(2+) responses in the adjoining cell
      when compared with the depolarized cell. The results were contrary to our earlier
      observation of heightened responses in the adjoining cell of the astrocyte pair,
      in cells pretreated with glutamate alone. The attenuated Ca(2+) responses in
      astrocytes would imply decrease in the vesicular release of glutamate and ATP.
      Extracellular glutamate concentration dependent regulation of the Ca(2+)
      signaling mechanism thus seems to operate in astrocytes, which may be important
      in regulating the neurotoxic accumulation of glutamate in the extracellular space
      and the synapse.

PMID- 18037245
TI  - Suppression of the inducible form of nitric oxide synthase prior to traumatic
      brain injury improves cytochrome c oxidase activity and normalizes cellular
      energy levels.
AB  - We have previously shown that the observed immediate increase in nitric oxide
      (NO) plays a significant role in the control of the cerebral microcirculation
      following traumatic brain injury (TBI). However, a second consequence of
      increased NO production after TBI may be impaired mitochondrial function, due to
      the fact that NO is a well-known inhibitor of cytochrome c oxidase (CcO). CcO is
      a key enzyme of the mitochondrial oxidative phosphorylation (OxPhos) machinery,
      which creates cellular energy in the form of ATP. NO competes with oxygen at the
      heme a(3)-Cu(B) reaction center of CcO. We thus hypothesized that TBI triggers
      inhibition of CcO, which would in turn lead to a decreased energy production by
      OxPhos at a time of an elevated energy demand for tissue remodeling. Here we show
      that TBI as induced by an acceleration weight drop model of diffuse brain injury
      in rats leads to CcO inhibition and dramatically decreased ATP levels in brain
      cortex. CcO inhibition can be partially restored by application of iNOS antisense
      oligonucleotides prior to TBI, which leads to a normalization of ATP levels
      similar to the controls. We propose that a lack of energy after TBI caused by
      inhibition of CcO is an important aspect of trauma pathology.

PMID- 18037247
TI  - Lower levels of prepulse inhibition of startle response in pregnant women
      compared to postpartum women.
AB  - OBJECTIVE: During the postpartum period, estradiol and progesterone levels
      decline from very high levels during late pregnancy to low levels within 48h of
      parturition. This period is associated with dysphoric states such as the
      postpartum blues. Animal studies have suggested an enhanced acoustic startle
      response and deficient prepulse inhibition (PPI) of startle response following
      progesterone withdrawal and during the postpartum period. The aim of the current
      study was to compare acoustic startle response and PPI in healthy third trimester
      pregnant women and healthy postpartum women. METHODS: Twenty-eight healthy
      pregnant and 21 healthy postpartum women (examined between 48h and 1 week after
      delivery) were recruited for the study. In addition, to evaluate the time-course
      of postpartum changes 11 early postpartum women (examined within 48h following
      delivery) were included in the study. The eyeblink component of the acoustic
      startle reflex was assessed using electromyographic measurements of m.
      Orbicularis Oculi. Twenty pulse-alone trials (115dB 40ms broad-band white noise)
      and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a
      115dB 40ms noise burst preceded at a 100ms interval by 20ms prepulses that were
      72, 74, 78 or 86dB. RESULTS: Pregnant women exhibited lower levels of PPI
      compared to late postpartum women, p<0.05. There was no difference between
      pregnant women and postpartum women examined within 48h of delivery. There was no
      difference in startle response or habituation to startle response between
      pregnant women and either of the two groups of postpartum women. CONCLUSION:
      Healthy women display lower levels of PPI during late pregnancy when estradiol
      and progesterone levels are high compared to the late postpartum period when
      ovarian steroid levels have declined.

PMID- 18037248
TI  - Pulmonary artery sarcoma and chronic thromboembolism.
AB  - Pulmonary artery sarcoma is a rare and highly lethal disease whose clinical
      findings are often indistinguishable from those of chronic thromboembolic
      pulmonary hypertension. Partial improvement after thrombolytic therapy has
      suggested that thromboembolic phenomena may be superimposed on the tumor, but, to
      date, a well-documented statement of these events has not been provided.

PMID- 18037249
TI  - Breast cancer risk assessment and management in primary care: provider attitudes,
      practices, and barriers.
AB  - BACKGROUND: We surveyed primary care providers to evaluate breast cancer risk
      assessment and management practices. METHODS: Primary care providers included
      staff (attendees, fellows, nurse practitioners) and residents practicing >or=1
      session/week in an outpatient general medicine practice or community practices.
      Of 201 eligible providers, 107 (53%) completed a self-administered questionnaire
      ascertaining attitudes, perceived barriers, and clinical practices related to
      assessing and managing breast cancer risk. RESULTS: Of providers, 96% mostly or
      definitely agreed that assessing breast cancer risk was a primary care provider's
      responsibility. In assessing risk, most providers reported usually or always
      asking about family history (71%), but fewer usually or always ask about parity
      (48%), biopsies (40%), or menarche (35%), and most never calculate Gail scores
      (76%). In managing women at high risk for breast cancer, many providers reported
      usually or always communicating increased risk to patients (58%) and tailoring
      screening based on risk (53%); however fewer providers usually or always discuss
      chemoprevention (13%) or genetic testing (16%) or refer to specialists (35%).
      Addressing more immediate issues (25%) and lacking confidence in knowledge of
      risk and risk assessment (20%) were the most commonly reported barriers to
      assessing risk (n=83). CONCLUSION: Primary care providers generally assess breast
      cancer risk primarily using family history, potentially missing women at
      increased risk based on other criteria. In addition, although providers tailor
      screening and refer women at high risk to specialists, they infrequently discuss
      chemoprevention or genetic testing. Addressing perceived barriers to assessing
      risk may improve care.

PMID- 18037250
TI  - Parathyroid hormone secretion in women in late menopause submitted to EDTA
      induced hypocalcemia.
AB  - OBJECTIVE: The physiological role of parathormone (PTH) in the maintenance of
      bone mass in humans has not been fully defined. The main objective of the present
      study was to evaluate basal and EDTA-stimulated PTH levels in young women (Group
      Y=30.9 years, N=7) and in women in late menopause (Group M=64.7 years, N=7) and
      their relationship to bone mineral density. METHODS: The PTH secretion test was
      performed by induction of hypocalcemia through intravenous administration of EDTA
      for 2h. Blood samples were collected every 10 min and used for ionic calcium and
      PTH measurements. During the basal period, an additional sample was collected for
      the determination of osteocalcin, FSH, and estradiol. A sample of early morning
      second voided urine was collected for analysis of deoxypiridinoline and
      creatinine as well as bone mass density (BMD) was determined by dual X-ray energy
      absorptiometry (DEXA). RESULTS: The aged patients presented lower femoral BMD
      (Y=0.860 g/cm(2) vs. M=0.690 g/cm(2), p<0.01), with four of them having a T score
      lower than -2.5 S.D. Basal, and during the EDTA infusion, PTH values were similar
      in both groups. However, among aged volunteers, the rise in PTH levels was higher
      for subjects with normal bone mass (NM: peak=236 pg/ml) than for subjects with
      osteoporosis (OM: peak=134.4 pg/ml). CONCLUSIONS: The present results suggest
      that PTH can have a modulating effect on the rate of bone loss during late
      menopause.

PMID- 18037251
TI  - Evaluation of in vivo dissolution behavior and GI transit of griseofulvin, a BCS
      class II drug.
AB  - Mean plasma concentration-time profile of griseofulvin, a BCS class II drug,
      orally administered as powders into rats, was predicted based on GITA model.
      However, it was very difficult to predict the individual plasma profile because
      of large inter-individual difference. As the absorption of griseofulvin would be
      rate-limited by the dissolution process, we tried to analyze the in vivo
      dissolution kinetics of griseofulvin by focusing on gastric emptying and
      intestinal transit as physiological factors influencing the in vivo dissolution
      kinetics. After oral administration of griseofulvin, theophylline and
      sulfasalazine into rats, gastric emptying and intestinal transit were
      simultaneously estimated by analyzing the absorption kinetics of theophylline and
      observing the appearance of sulfapyridine in plasma, respectively. Gastric
      emptying kinetics was not significantly correlated with absorption or dissolution
      behavior of griseofulvin. On the other hand, the cecum-arriving time reflecting
      the intestinal transit was significantly correlated with both AUC and total
      dissolved amount of griseofulvin. T(max) of griseofulvin also increased with the
      increase of cecum-arriving time. These results clearly indicate that the longer
      residence time could lead to the higher dissolution and absorption of
      griseofulvin and that the variance of intestinal transit could be responsible for
      the inter-individual difference of the in vivo absorption behavior.

PMID- 18037252
TI  - Cochlear implant electrode configuration effects on activation threshold and
      tonotopic selectivity.
AB  - The multichannel design of contemporary cochlear implants (CIs) is predicated on
      the assumption that each channel activates a relatively restricted and
      independent sector of the deaf auditory nerve array, just as a sound within a
      restricted frequency band activates a restricted region of the normal cochlea The
      independence of CI channels, however, is limited; and the factors that determine
      their independence, the relative overlap of the activity patterns that they
      evoke, are poorly understood. In this study, we evaluate the spread of activity
      evoked by cochlear implant channels by monitoring activity at 16 sites along the
      tonotopic axis of the guinea pig inferior colliculus (IC). "Spatial tuning
      curves" (STCs) measured in this way serve as an estimate of activation spread
      within the cochlea and the ascending auditory pathways. We contrast natural
      stimulation using acoustic tones with two kinds of electrical stimulation either
      (1) a loose fitting banded array consisting of a cylindrical silicone elastomer
      carrier with a linear series of ring contacts; or (2) a space-filling array
      consisting of a tapered silicone elastomer carrier that is designed to fit snugly
      into the guinea pig scala tympani with a linear series of ball contacts
      positioned along it Spatial tuning curves evoked by individual acoustic tones,
      and by activation of each contact of each array as a monopole, bipole or tripole
      were recorded. Several channel configurations and a wide range of electrode
      separations were tested for each array, and their thresholds and selectivity were
      estimated. The results indicate that the tapered space-filling arrays evoked more
      restricted activity patterns at lower thresholds than did the banded arrays.
      Monopolar stimulation (one intracochlear contact activated with an extracochlear
      return) using either array evoked broad activation patterns that involved the
      entire recording array at current levels <6dBSL, but at relatively low
      thresholds. Bi- and tri-polar configurations of both array types evoked more
      restricted activity patterns, but their thresholds were higher than those of
      monopolar configurations. Bipolar and tripolar configurations with closely spaced
      contacts evoked activity patterns that were comparable to those evoked by pure
      tones. As the spacing of bipolar electrodes was increased (separations >1mm), the
      activity patterns became broader and evoked patterns with two distinct threshold
      minima, one associated with each contact.

PMID- 18037253
TI  - Evaluation of antimicrobial, antioxidant and wound-healing potentials of
      Holoptelea integrifolia.
AB  - The methanolic extracts of Holoptelea integrifolia (Roxb.) (Urticaceae) leaves
      (MLE) and stem bark (MSBE) were studied for the wound-healing potential. Since
      wound healing is severely hampered by microbial infection and reactive oxygen
      species (ROS), this study was undertaken to evaluate antimicrobial and
      antioxidant activity apart from wound-healing activity. The antimicrobial
      property of the Holoptelea was studied against the six bacterial and five fungal
      strains using the agar well diffusion method and minimum microbicidal
      concentration and minimum inhibitory concentration were determined for each
      strain, in which methanolic extract of stem bark (MSBE) has shown bigger zone of
      inhibition (11.3-20.4 mm) than methanolic extract of leaves (MLE) (9.6-14.9 mm).
      The anti-oxidant activity was evaluated by DPPH free radical scavenging activity
      using HPLC method. The IC(50) values obtained for MSBE (TPC: 78.53+/-1.26 mg/g)
      and MLE (TPC: 57.71+/-1.45 mg/g) were 37.66+/-0.48 and 50.36+/-0.59 microg/well,
      respectively. In excision wound model, more than 90% wound healing was recorded
      in treated groups by 14 days of post surgery, where as only 62.99% was observed
      in the control group. In incision model, higher breaking strengths and higher
      hydroxyproline content in treated groups suggested higher collagen re-deposition
      than the control group. Finally, histopathology studies conformed wound-healing
      activity of Holoptelea integrifolia.

PMID- 18037254
TI  - Objective and non-invasive evaluation of dry mouth.
AB  - OBJECTIVE: This study was designed to evaluate the moisture checker (MucusIII), a
      new device for measuring moisture of the oral submucosa. METHODS: Defective
      salivary secretion was induced by sialoadenectomy (n=8), while the remaining five
      guinea pigs underwent sham surgery (control group). We measured the unstimulated
      salivary flow rate, wetness of the oral mucosa using the oral tester (L-SALIVO)
      and moisture of the submucosa of the tongue using MucusIII. All tests were
      performed before (baseline) and 1 month after surgery. RESULTS: Sialoadenectomy
      significantly reduced both the salivary flow rate and the tester reading at 10
      and at 30s (p<0.01). The vale due to the MucusIII as significantly reduced in
      animals with sialoadenectomy (p<0.01). CONCLUSION: The MucusIII is a device for
      objective evaluation of the moisture of the oral cavity.

PMID- 18037255
TI  - Visceral leishmaniasis with portal hypertension mimicking auto immune hepatitis.

PMID- 18037256
TI  - Vascular endothelial growth factor and its soluble receptor in benign and
      malignant ovarian tumors.
AB  - An imbalance between pro-angiogenic and anti-angiogenic factors is hypothesized
      in the pathogenesis of ovarian cystic disease. The aim of the following study was
      to explore the possible role of free vascular endothelial growth factor receptor
      1 (sVEGFR-1), a soluble regulator of vascular endothelial growth factor (VEGF)
      action, in ovarian cystoadenoma, endometriomata and cystoadenocarcinoma. Forty
      eight women, of whom fourteen had ovarian serous cysts, twenty-eight had stage
      III-IV ovarian endometriomata, and six had stage IIIB-IIIC ovarian carcinoma,
      were included. Sampling of serum, peritoneal and ovarian cystic fluids and of
      tumor tissue was performed before, during and following surgery, respectively.
      Levels of VEGF and sVEGFR-1 were measured in serum, peritoneal and cystic fluid.
      VEGF and sVEGFR-1 expression was evaluated in tumor tissue. There were no
      differences in serum VEGF and sVEGFR-1 levels nor in VEGF/VEGFR-1 ratio between
      study groups. Peritoneal fluid VEGF levels were higher in cystoadenocarcinoma
      patients than in endometriosis and in cystoadenoma patients, while sVEGFR-1
      peritoneal fluid concentrations were significantly higher only in endometriosis
      affected women. VEGF/VEGFR-1 ratio was highest in the peritoneal fluid of cancer
      patients with respect to the other two groups of women. Cystic fluid VEGF and
      VEGFR-1 concentrations were higher in endometriomata and in cystoadenocarcinomas
      than in cystadenomas but the VEGF/VEGFR-1 ratio was highest in cancer patients.
      Western blot evidenced a marked expression of VEGF and soluble VEGFR-1 in
      endometriosis tissue with respect to benign cyst tissue but a lower expression of
      both molecules, contrary to that expected, in cancer tissue. In conclusion, all
      in all, our data indicate that an excess of local VEGF with respect to its
      soluble receptor VEGFR-1 may be a key factor in the onset and maintenance of
      pathological neo-angiogenesis in ovarian cyst formation.

PMID- 18037257
TI  - [Prevention of heel pressure sores with a foam body-support device. A randomized
      controlled trial in a medical intensive care unit].
AB  - BACKGROUND: To assess in a prospective controlled study the efficacy and safety
      of a specific foam body-support device designed as to prevent heel pressure
      ulcers. METHODS: A randomization table was used to allocate 70 patients into 2
      groups. The control group was treated with our standard pressure sore prevention
      protocol (half-seated position, water-mattress and preventive massages 6 times a
      day); the experimental group was treated with the same standard protocol as well
      as with the foam body-support device being evaluated. Patients were included if
      their Waterlow score was >10, indicating a high risk of developing pressure
      ulcers and if they had no skin lesion on the heels. Foam devices, covered with
      jersey, were constructed for the legs and allowed the heels to be free of any
      contact with the bed; another foam block was arranged perpendicularly to the
      first, in contact with the soles, to prevent ankles from assuming an equinus
      position (to prevent a dropfoot condition). The principal criterion for efficacy
      was the number of irreversible skin lesions on the heel (that is, beyond the
      stage of blanching hyperemia, reversible after finger pressure); these lesions
      were assessed every day until the end of the study (up to 30 days). FINDINGS: The
      number of irreversible heel pressure ulcers was lower in the experimental (3
      patients, 8.6%) than in the control group (19 patients, 55.4%) (p<0.0001). Mean
      time without any pressure ulcer was higher in the experimental group (5.6 days,
      compared with 2.8 days, p=0.01). The groups did not differ in the number of
      pressure sores on the sacrum and leg. CONCLUSION: An anatomical foam body-support
      is effective in preventing heel pressure ulcers in patients on a medical
      intensive care unit and is well tolerated.

PMID- 18037258
TI  - [Vitamin D deficiency in elderly men living in urban areas, at home or in
      institutions].
AB  - OBJECTIVES: Many studies report severe vitamin D deficiency in the elderly and
      its involvement in various health problems (not limited to bone metabolism
      disorders). Most papers concern elderly women, however, and little is known about
      this problem among elderly men. This study focused on vitamin D deficiency in
      elderly men living in urban areas, whether at home or in an institution. METHODS:
      Between December 2005 and June 2006, we randomly recruited from general practices
      336 men aged 65 years or more, living either at home or in institutions for the
      elderly. The variables studied were: age, residence (home or institution), fall
      and fracture history, independence (Katz), mobility (TUG), balance, outdoor
      walking, blood 25-OH-D level, glomerular filtration rate (MDRD) and PINI index.
      RESULTS: Of the 336 men, 45 (13%) were excluded because they were already
      receiving vitamin D treatment. The study thus included 291 patients, 174
      community-dwelling and 117 institutionalized. The latter were significantly older
      and had less independence. Their 25-OH-D levels were also significantly lower
      than for community-dwelling subjects. The prevalence of severe vitamin D
      deficiency (25-OH-D < 12 ng/mL) was 79% among men in institutions and 57% among
      those living in the community (p<0.0001), and for mild and moderate vitamin D
      deficiency (12-32 ng/mL), 21% and 42%, respectively. Overall, only 2 men, both
      living at home, had normal vitamin D levels (25-OH-D > or = 32 ng/mL). In
      institutions, factors predictive of severe deficiency were TUG > or = 30s,
      walking distance < or = 100 m and lack of outdoor walking. Among the men living
      at home, none of the variables studied was associated with severe vitamin D
      deficiency. DISCUSSION: Potential biases of the study are discussed. Seasonal
      variations of vitamin D levels were small and comparable in both groups. The
      study confirms the high prevalence of vitamin D deficiency in elderly men. These
      results could probably be extended to other European cities with similar
      characteristics. The problem of interpreting 25-OH-D results with respect to
      current laboratory norms for defining severe or moderate vitamin D deficiency (12
      and 32 ng/mL, respectively) is also discussed. CONCLUSION: Vitamin D deficiency
      is widespread and severe in elderly men, especially those living in institutions.
      Moderate to severe deficiency is also frequent among men living at home. Vitamin
      D supplementation should be routinely prescribed in institutions for the elderly
      and probably also to any individual over 65 years. Laboratory norms should be
      harmonized and consistent with recent medical evidence.

PMID- 18037259
TI  - [Economic aspects of severe asthma].
AB  - Severe asthma and difficult-to-treat asthma are major issues in public health,
      given the mortality and morbidity they induce and their detrimental effects on
      patients' quality of life. The economic consequences should not be overlooked
      either. Published studies suggest that asthma-related medical resource use
      increases with the degree of asthma severity. Medical resource use incurred by
      severe (and/or difficult-to-treat) asthma could be reduced in part by more
      appropriate treatment, better patient education, improved coordination of disease
      management and treatment of comorbid diagnoses. The specific difficulties in the
      management of severe asthma and/or difficult-to-treat asthma must nonetheless be
      kept in mind. Recent new treatments appear promising, but their costs and
      indications in actual medical practice require better definition.

PMID- 18037260
TI  - [New frontiers in multiple sclerosis].

PMID- 18037261
TI  - Trypanosoma cruzi heparin-binding proteins and the nature of the host cell
      heparan sulfate-binding domain.
AB  - Trypanosoma cruzi invasion is mediated by receptor-ligand recognition between the
      surfaces of both parasite and target cell. We have previously demonstrated the
      role of heparan sulfate proteoglycan in the attachment and invasion of T. cruzi
      in cardiomyocytes. Herein, we have isolated the T. cruzi heparin-binding proteins
      (HBP-Tc) and investigated the nature of cardiomyocyte heparan sulfate (HS)
      binding site to the parasite surface ligand. Two major heparin-binding proteins
      with molecular masses of 65.8 and 59 kDa were observed in total extract of
      amastigote and trypomastigote forms of T. cruzi. Hydrophobic [S(35)]methionine
      labeled proteins eluted from heparin-sepharose affinity chromatography also
      revealed both proteins in trypomastigotes but only the 59 kDa is strongly
      recognized by biotin-conjugated glycosaminoglycans. Competition assays were
      performed to analyze the role of sulfated proteoglycans, including heparin,
      keratan sulfate and both acetylated and highly sulfated domains of heparan
      sulfate, in the recognition and invasion process of T. cruzi. Significant
      inhibitions of 84% and 35% in the percentage of infection were revealed after
      treatment of the parasites with heparin and the N-acetylated/ N-sulfated heparan
      sulfate domain, respectively, suggesting the important role of the glycuronic
      acid and NS glucosamine domain of the HS chain in the recognition of the HBP-Tc
      during the T. cruzi-cardiomyocyte interaction.

PMID- 18037262
TI  - Mutations in the periplasmic chaperone leading to loss of surface expression of
      the colonization factor CS6 in enterotoxigenic Escherichia coli (ETEC) clinical
      isolates.
AB  - Enterotoxigenic Escherichia coli (ETEC) cause diarrhoea by adhesion to human
      enterocytes by one or more colonization factors (CFs) and secretion of heat
      labile (LT) and/or heat-stable (ST) enterotoxins. Expression of coli surface
      antigen 6 (CS6) on the bacterial surface, usually associated with ETEC strains
      that produce ST alone or in combination with LT, is rarely found in strains
      expressing only LT. However, a number of LT-only strains which are genotypically
      positive but phenotypically negative for CS6 have been identified. In this study,
      eight such strains from India and Guinea-Bissau belonging to different clones
      were analysed. The CS6 operon cssABCD was transcribed but protein analyses
      suggested that the structural subunits CssA and CssB of CS6 were absent in the
      periplasm. Most strains contained truncating mutations within the periplasmic
      chaperone-encoding gene cssC and protein modelling indicated that this severely
      affected the substrate-binding capacity of the chaperone. A single-nucleotide
      polymorphism (SNP) (A-->T) in the 5'-untranslated region of cssC distinguished
      the eight strains from ETEC strains that do express CS6 on the surface and may be
      a potential marker for ETEC strains containing phenotypically silent cssABCD. The
      study emphasizes the importance of using both genotypic and phenotypic methods in
      epidemiological studies of ETEC, e.g. for vaccine development.

PMID- 18037265
TI  - Case study for identification of potentially indel-caused alternative expression
      isoforms in the rice subspecies japonica and indica by integrative genome
      analysis.
AB  - Alternative splicing (AS) is one of the most significant components of the
      functional complexity of the eukaryote genome, increasing protein diversity,
      creating isoforms, and affecting mRNA stability. Recently, whole genome sequences
      and large microarray data sets have become available, making data integration
      feasible and allowing the study of the possible regulatory mechanism of AS in
      rice (Oryza sativa) by erecting and testing hypotheses before doing bench
      studies. We have developed a new strategy and have identified 215 rice genes with
      alternative expression isoforms related to insertion and deletion (indel) between
      subspecies indica and subspecies japonica. We did a case study for alternative
      expression isoforms of the rice peroxidase gene LOC_Os06g48030 to investigate
      possible mechanisms by which indels caused alternative splicing between the
      indica and the japonica varieties by mining of array data together with
      validation by RT-PCR and genome sequencing analysis. Multiple poly(A) signals
      were detected in the specific indel region for LOC_Os06g48030. We present a new
      methodology to promote more discoveries of potentially indel-caused AS genes in
      rice, which may serve as the foundation for research into the regulatory
      mechanism of alternative expression isoforms between subspecies.

PMID- 18037263
TI  - Molecular characterization of a functional type VI secretion system from a
      clinical isolate of Aeromonas hydrophila.
AB  - Our laboratory recently molecularly characterized the type II secretion system
      (T2SS)-associated cytotoxic enterotoxin (Act) and the T3SS-secreted AexU effector
      from a diarrheal isolate SSU of Aeromonas hydrophila. The role of these toxin
      proteins in the pathogenesis of A. hydrophila infections was subsequently
      delineated in in vitro and in vivo models. In this study, we characterized the
      new type VI secretion system (T6SS) from isolate SSU of A. hydrophila and
      demonstrated its role in bacterial virulence. Study of the role of T6SS in
      bacterial virulence is in its infancy, and there are, accordingly, only limited,
      recent reports directed toward a better understanding its role in bacterial
      pathogenesis. We have provided evidence that the virulence-associated secretion
      (vas) genes vasH (Sigma 54-dependent transcriptional regulator) and vasK
      (encoding protein of unknown function) are essential for expression of the genes
      encoding the T6SS and/or they constituted important components of the T6SS.
      Deletion of the vasH gene prevented expression of the potential translocon
      hemolysin coregulated protein (Hcp) encoding gene from bacteria, while the vasK
      gene deletion prevented secretion but not translocation of Hcp into host cells.
      The secretion of Hcp was independent of the T3SS and the flagellar system. We
      demonstrated that secreted Hcp could bind to the murine RAW 264.7 macrophages
      from outside, in addition to its ability to be translocated into host cells.
      Further, the vasH and vasK mutants were less toxic to murine macrophages and
      human epithelial HeLa cells, and these mutants were more efficiently phagocytosed
      by macrophages. We also provided evidence that the expression of the hcp gene in
      the HeLa cell resulted in apoptosis of the host cells. Finally, the vasH and vasK
      mutants of A. hydrophila were less virulent in a septicemic mouse model of
      infection, and animals immunized with recombinant Hcp were protected from
      subsequent challenge with the wild-type (WT) bacterium. In addition, mice
      infected with the WT A. hydrophila had circulating antibodies to Hcp, indicating
      an important role of T6SS in the pathogenesis of A. hydrophila infections. Taken
      together, we have characterized the T6SS from Aeromonas for the first time and
      provided new features of this secretion system not yet known for other pathogens.

PMID- 18037264
TI  - Transcriptional profiling of murine organ genes in response to infection with
      Bacillus anthracis Ames spores.
AB  - Bacillus anthracis is the Gram-positive, spore-forming etiological agent of
      anthrax, an affliction studied because of its importance as a potential
      bioweapon. Although in vitro transcriptional responses of macrophages to either
      spore or anthrax toxins have been previously reported, little is known regarding
      the impact of infection on gene expression in host tissues. We infected Swiss
      Webster mice intranasally with 5 LD(50) of B. anthracis-virulent Ames spores and
      observed the global transcriptional profiles of various tissues over a 48 h time
      period. RNA was extracted from spleen, lung, and heart tissues of infected and
      control mice and examined by Affymetrix GeneChip analysis. Approximately 580 host
      genes were significantly over or under expressed among the lung, spleen, and
      heart tissues at 8 and 48 h time points. Expression of genes encoding for
      surfactant and major histocompatibility complex (MHC) presentation was diminished
      during the early phase of infection in lungs. By 48 h, a significant number of
      genes were modulated in the heart, including up-regulation of calcium-binding
      related gene expression, and down-regulation of multiple genes related to cell
      adhesion, formation of the extracellular matrix, and the cell cytoskeleton.
      Interestingly, the spleen 8h post-infection showed striking increases in the
      expression of genes that encode hydrolytic enzymes, and these levels remained
      elevated throughout infection. Further, genes involving antigen presentation and
      interferon responses were down-regulated in the spleen at 8 h. In late stages of
      infection, splenic genes related to the inflammatory response were up-regulated.
      This study is the first to describe the in vivo global transcriptional response
      of multiple organs during inhalational anthrax. Although numerous genes related
      to the host immunological response and certain protection mechanisms were up
      regulated in these organs, a vast list of genes important for fully developing
      and maintaining this response were decreased. Additionally, the lung, spleen, and
      heart showed differential responses to the infection, further validating the
      demand for a better understanding of anthrax pathogenesis in order to design
      therapies against novel targets.

PMID- 18037266
TI  - Social status modulates basal IL-1 concentrations in the hypothalamus of pair
      housed rats and influences certain features of stress reactivity.
AB  - Recent findings from our laboratory and others indicate that exposure to stress
      can increase expression of the pro-inflammatory cytokine interleukin-1 (IL-1). In
      a series of studies examining this response, we observed pronounced differences
      in baseline levels of hypothalamic IL-1 of pair-housed rats. We hypothesized that
      these pair-wise differences might be a result of prolonged social stress
      associated with dominance/submissiveness, and that the submissive animal would
      show heightened baseline levels of IL-1. In order to test this hypothesis, we
      utilized a food competition paradigm (access to cheerios) to assess dominance
      within a dyad prior to the assessment of hypothalamic IL-1 levels. Based on the
      results of this test, clear dominance hierarchies were observed in approximately
      50% of the dyads, a ratio comparable to what has been reported previously. More
      importantly, this dominant/submissive categorization could be used to predict
      pair-wise differences in hypothalamic IL-1 with greater than 90% accuracy.
      Specifically, the submissive rat in each dyad (determined a priori) consistently
      evinced hypothalamic IL-1 levels that were nearly double that of its dominant
      cage mate. Further studies demonstrated that submissive rats showed a more rapid
      and pronounced hyperthermic response to novel environment stress relative to
      dominant rats. Interestingly, social status had no effect on corticosterone
      reactivity, even when the nature and intensity of the stressor was varied.
      Finally, maintenance of a clear dominance hierarchy obfuscated hypothalamic IL-1
      responses to footshock exposure, with the most robust increases in hypothalamic
      IL-1 provoked by footshock being observed in pairs where there was no clear
      dominance hierarchy. Together, these findings suggest that social status can have
      a significant impact on stress reactivity and neuroimmune consequences of
      stressor exposure even in the unperturbed home cage environment.

PMID- 18037267
TI  - GPR26: a marker for primary glioblastoma?
AB  - Glioblastomas are highly malignant brain tumours; they have been described as one
      of the most deadly human cancers. Two conceptual classifications of the condition
      exist: primary (de novo), which does not exhibit prior disease and secondary
      glioblastoma, which develops from a pre-existing glioma. This study investigates
      whether GPR26 is differentially transcribed in glioblastoma tissue from patients
      of different ages, in order to define a candidate genetic marker. The
      transcriptional profile of GPR26 was compared in nine samples: seven glioblastoma
      tissues and two normal brain tissues using PCR. Despite GPR26 being present in
      the glioblastoma tissues, it was not transcribed in any of the four cell lines
      tested. GPR26 transcription ratios were compared between normal and cancerous
      samples, also age categories <50 and >60 years were compared. Results suggested
      differential transcription of GPR26, which is significantly less transcribed in
      tissues from older patients, implied by a p-value of 0.03. This study has
      identified GPR26 to be a genetic indicator of primary glioblastoma, suggesting
      that it could be a suppressor of primary glioblastoma development.

PMID- 18037268
TI  - A systematic review of challenging behaviors in children exposed prenatally to
      substances of abuse.
AB  - A review of the existing literature on the occurrence of challenging behavior
      among children with prenatal drug exposure was conducted. While a large number of
      studies were identified that evaluated various outcomes of prenatal drug
      exposure, only 37 were found that directly evaluated challenging behaviors. Of
      the 37 studies, 23 focused on prenatal cocaine exposure, and 14 focused on
      prenatal alcohol exposure; most studies relied on broadband measures such as the
      CBCL for the assessment of challenging behavior. Among the 37 studies, a clear
      role for the postnatal environment on developing challenging behaviors was
      evident; however, prenatal alcohol exposure showed a much clearer independent
      effect upon challenging behaviors than was noted in the prenatal cocaine studies.
      Additionally, only 3 of the 37 studies addressed interventions for challenging
      behaviors, each of which showed an improvement in child behavior or parent-child
      interactions. As researchers have continued to show the importance of the
      postnatal environment, it is likely that interventions addressing specific
      environmental risk factors will be helpful to reduce or prevent challenging
      behaviors among this population.

PMID- 18037269
TI  - Treatment of challenging behavior exhibited by children with prenatal drug
      exposure.
AB  - A large body of literature exists describing the harmful effects of prenatal drug
      exposure on infant and child development. However, there is a paucity of research
      examining strategies to ameliorate sequelae such as externalizing behavior
      problems. In the present study, functional analysis procedures were used to
      assess challenging behavior exhibited by two children who were prenatally exposed
      to drugs of abuse. Results for both children indicated that challenging behavior
      was maintained by access to positive reinforcement (adult attention and tangible
      items). For one child, challenging behavior was also maintained by negative
      reinforcement (escape from activities of daily living). Function-based
      interventions were effective in reducing challenging behavior for both children.
      Implications for utilizing methods of applied behavior analysis in research with
      children with prenatal drug exposure are discussed.

PMID- 18037270
TI  - Performer's attitudes toward seeking health care for voice issues: understanding
      the barriers.
AB  - Contemporary commercial music (CCM) performers rely heavily on their voice, yet
      may not be aware of the importance of proactive voice care. This investigation
      intends to identify perceptions and barriers to seeking voice care among CCM
      artists. This cross-sectional observational study used a 10-item Likert-based
      response questionnaire to assess current perceptions regarding voice care in a
      population of randomly selected participants of professional CCM conference.
      Subjects (n=78) were queried regarding their likelihood to seek medical care for
      minor medical problems and specifically problems with their voice. Additional
      questions investigated anxiety about seeking voice care from a physician
      specialist, speech language pathologist, or voice coach; apprehension regarding
      findings of laryngeal examination, laryngeal imaging procedures; and the effect
      of medical insurance on the likelihood of seeking medical care. Eighty-two
      percent of subjects reported that their voice was a critical part of their
      profession; 41% stated that they were not likely to seek medical care for
      problems with their voice; and only 19% were reluctant to seek care for general
      medical problems (P<0.001). Anxiety about seeking a clinician regarding their
      voice was not a deterrent. Most importantly, 39% of subjects do not seek medical
      attention for their voice problems due to medical insurance coverage. The CCM
      artists are less likely to seek medical care for voice problems compared with
      general medical problems. Availability of medical insurance may be a factor.
      Availability of affordable voice care and education about the importance of voice
      care is needed in this population of vocal performers.

PMID- 18037271
TI  - Medical image retrieval with probabilistic multi-class support vector machine
      classifiers and adaptive similarity fusion.
AB  - We present a content-based image retrieval framework for diverse collections of
      medical images of different modalities, anatomical regions, acquisition views,
      and biological systems. For the image representation, the probabilistic output
      from multi-class support vector machines (SVMs) with low-level features as inputs
      are represented as a vector of confidence or membership scores of pre-defined
      image categories. The outputs are combined for feature-level fusion and retrieval
      based on the combination rules that are derived by following Bayes' theorem. We
      also propose an adaptive similarity fusion approach based on a linear combination
      of individual feature level similarities. The feature weights are calculated by
      considering both the precision and the rank order information of top retrieved
      relevant images as predicted by SVMs. The weights are dynamically updated by the
      system for each individual search to produce effective results. The experiments
      and analysis of the results are based on a diverse medical image collection of
      11,000 images of 116 categories. The performances of the classification and
      retrieval algorithms are evaluated both in terms of error rate and precision
      recall. Our results demonstrate the effectiveness of the proposed framework as
      compared to the commonly used approaches based on low-level feature descriptors.

PMID- 18037272
TI  - Macrophage migration inhibitory factor (MIF) in bullous pemphigoid.

PMID- 18037273
TI  - Association of PTPN22 1858C/T polymorphism with vitiligo susceptibility in
      Gujarat population.

PMID- 18037274
TI  - Ivermectin: 25 years and still going strong.
AB  - Ivermectin is a drug that many people will never have heard of. Yet thousands of
      villagers of all ages in communities scattered throughout the remotest parts of
      Africa and Latin America know its name, and some experts regard it as one of the
      greatest health interventions of the past 50 years. Ivermectin was brought to the
      commercial market place for multi-purpose use in animal health in 1981. Six years
      later it was registered for human use. This remarkable compound has improved the
      lives and productivity of billions of humans, livestock and pets around the
      globe, and promises to help consign to the history books two devastating and
      disfiguring diseases that have plagued people throughout the tropics for
      generations--while new uses for it are continually being found.

PMID- 18037275
TI  - Olfactomedin-2 mediates development of the anterior central nervous system and
      head structures in zebrafish.
AB  - Olfactomedins comprise a diverse family of secreted glycoproteins, which includes
      noelin, tiarin, pancortin and gliomedin, implicated in development of the nervous
      system, and the glaucoma-associated protein myocilin. Here we show in zebrafish
      that olfactomedin-2 (OM2) is a developmentally regulated gene, and that knockdown
      of protein expression by morpholino antisense oligonucleotides leads to
      perturbations of nervous system development. Interference with OM2 expression
      results in impaired development of branchiomotor neurons, specific disruption of
      the late phase branchiomotor axon guidance, and affects development of the caudal
      pharyngeal arches, olfactory pits, eyes and optic tectum. Effects of OM2
      knockdown on eye development are likely associated with Pax6 signaling in
      developing eyes, as Pax6.1 and Pax6.2 mRNA expression patterns are altered in the
      eyes of OM2 morphants. The specific absence of most cartilaginous structures in
      the pharyngeal arches indicates that the observed craniofacial phenotypes may be
      due to perturbed differentiation of cranial neural crest cells. Our studies show
      that this member of the olfactomedin protein family is an important regulator of
      development of the anterior nervous system.

PMID- 18037277
TI  - The immune system--is it relevant to cancer development, progression and
      treatment?
AB  - The ability of the immune system to effectively respond to human tumours is a
      matter of long-term controversy. There is an increasing body of recent evidence
      to support a role for the immune system in eliminating pre-clinical cancers, an
      old concept termed 'immunosurveillance'. 'Immunoediting' is an updated
      hypothesis, in which selection pressures applied by the immune response to
      tumours modulate tumour immunogenicity and growth. Tumour infiltration by immune
      cells has been shown to have powerful prognostic significance in a host of cancer
      types. Paradoxically, in some circumstances the immune system can promote tumour
      development. Cytotoxic therapies, including radiotherapy and chemotherapy, induce
      potentially immunogenic cell death, releasing tumour-associated antigens in the
      context of a 'danger' signal to the immune system. An understanding of the
      interaction between immune cells, tumour cells and treatment modalities will
      therefore guide the future combination of immunotherapy with conventional therapy
      to achieve optimal anti-tumour effects.

PMID- 18037276
TI  - Transformation of eye to antenna by misexpression of a single gene.
AB  - In Drosophila, the eye and antenna originate from a single epithelium termed the
      eye-antennal imaginal disc. Illumination of the mechanisms that subdivide this
      epithelium into eye and antenna would enhance our understanding of the mechanisms
      that restrict stem cell fate. We show here that Dip3, a transcription factor
      required for eye development, alters fate determination when misexpressed in the
      early eye-antennal disc, and have taken advantage of this observation to gain new
      insight into the mechanisms controlling the eye-antennal switch. Dip3
      misexpression yields extra antennae by two distinct mechanisms: the splitting of
      the antennal field into multiple antennal domains (antennal duplication), and the
      transformation of the eye disc to an antennal fate. Antennal duplication requires
      Dip3-induced under proliferation of the eye disc and concurrent over
      proliferation of the antennal disc. While previous studies have shown that
      overgrowth of the antennal disc can lead to antennal duplication, our results
      show that overgrowth is not sufficient for antennal duplication, which may
      require additional signals perhaps from the eye disc. Eye-to-antennal
      transformation appears to result from the combination of antennal selector gene
      activation, eye determination gene repression, and cell cycle perturbation in the
      eye disc. Both antennal duplication and eye-to-antennal transformation are
      suppressed by the expression of genes that drive the cell cycle providing support
      for tight coupling of cell fate determination and cell cycle control. The finding
      that this transformation occurs only in the eye disc, and not in other imaginal
      discs, suggests a close developmental and therefore evolutionary relationship
      between eyes and antennae.

PMID- 18037278
TI  - In vitro and in vivo evaluation of tegaserod maleate pH-dependent tablets.
AB  - The purpose of this study was to prepare tegaserod maleate (TM) pH-dependent
      tablets and evaluate their advantages as a sustained release delivery system. TM,
      insoluble in water and unstable in gastric milieu, was formulated into pH
      dependent tablets coated with combinations of two methacrylic acid copolymers -
      Eudragit L100 and Eudragit S100. The influence of core tablet compositions,
      polymer combination ratios and coating levels on the in vitro release rate of TM
      from coated tablets was investigated. The optimum formulation was evaluated for
      in vitro release rate and in vivo bioavailability study on beagle dogs. In
      addition, physico-chemical properties of the drug, including solubility at
      different pH and temperatures, and dissociation constant were determined. The
      results showed that no drug was released in 0.1 mol/L hydrochloric acid within
      2h, and about 90% of the drug was released in the pH 6.8 phosphate buffer within
      12h in a sustained manner. The pharmacokinetic investigation showed that TM pH
      dependent tablets exhibited a sustained plasma concentration, a lag time of
      approximately 2.3h and a relative bioavailability of 159% compared to plain
      tablets. A close correlation existed between the in vitro release rate of the pH
      dependent system and its in vivo absorption percentage. The results of the
      present study have demonstrated that the pH-dependent tablet system is a
      promising vehicle for preventing rapid hydrolysis in gastric milieu and improving
      oral bioavailability of TM for the treatment of irritable bowel syndrome.

PMID- 18037279
TI  - Antifungal photodynamic therapy.
AB  - In photodynamic antimicrobial chemotherapy (PACT), a combination of a sensitising
      drug and visible light causes selective destruction of microbial cells. The
      ability of light-drug combinations to kill microorganisms has been known for over
      100 years. However, it is only recently with the beginning of the search for
      alternative treatments for antibiotic-resistant pathogens that the phenomenon has
      been investigated in detail. Numerous studies have shown PACT to be highly
      effective in the in vitro destruction of viruses and protozoa, as well as Gram
      positive and Gram-negative bacteria and fungi. Results of experimental
      investigations have demonstrated conclusively that both dermatomycetes and yeasts
      can be effectively killed by photodynamic action employing phenothiazinium,
      porphyrin and phthalocyanine photosensitisers. Importantly, considerable
      selectivity for fungi over human cells has been demonstrated, no reports of
      fungal resistance exist and the treatment is not associated with genotoxic or
      mutagenic effects to fungi or human cells. In spite of the success of cell
      culture investigations, only a very small number of in vivo animal and human
      trials have been published. The present paper reviews the studies published to
      date on antifungal applications of PACT and aims to raise awareness of this area
      of research, which has the potential to make a significant impact in future
      treatment of fungal infections.

PMID- 18037280
TI  - An n-3 fatty acid deficient diet affects mouse spatial learning in the Barnes
      circular maze.
AB  - Deficiency in n-3 fatty acids has been accomplished through the use of an
      artificial rearing method in which ICR mouse pups were hand fed a deficient diet
      starting from the 2nd day of life. There was a 51% loss of total brain DHA in
      mice with an n-3 fatty acid-deficient diet relative to those with a diet
      sufficient in n-3 fatty acids. n-3 fatty acid adequate and deficient mice did not
      differ in terms of locomotor activity in the open field test or in anxiety
      related behavior in the elevated plus maze. The n-3 fatty acid-deficient mice
      demonstrated impaired learning in the reference-memory version of the Barnes
      circular maze as they spent more time and made more errors in search of an escape
      tunnel. No difference in performance between all dietary groups in the cued and
      working memory version of the Barnes maze was observed. This indicated that
      motivational, motor and sensory factors did not contribute to the reference
      memory impairment.

PMID- 18037281
TI  - Neuroprotective action of omega-3 polyunsaturated fatty acids against
      neurodegenerative diseases: evidence from animal studies.
AB  - Studies in animals clearly show that oral intake of docosahexaenoic acid (DHA)
      can alter brain DHA concentrations and thereby modify brain functions. This
      provides us with an opportunity to use DHA as a nutraceutical or pharmaceutical
      tool in brain disorders such as Alzheimer disease (AD) and Parkinson disease
      (PD). Most of the published epidemiological studies are consistent with a
      positive association between high reported DHA consumption or high DHA blood
      levels and a lower risk of developing AD later in life. Such observations have
      prompted the investigation of DHA in three different transgenic models of AD.
      These analyses show that animal models of AD are more vulnerable to DHA depletion
      than controls and that DHA exerts a beneficial effect against pathological signs
      of AD, including A beta accumulation, cognitive impairment, synaptic marker loss,
      and hyperphosphorylation of tau. Multiple mechanisms of action can be associated
      with the neuroprotective effects of DHA and include antioxidant properties and
      activation of distinct cell signaling pathways. Although the first randomized
      clinical assays have yet failed to demonstrate convincing beneficial effects of
      DHA for AD patients, the knowledge gathered in recent years holds out a hope for
      prevention and suggests that the elderly and people bearing a genetic risk for AD
      should at least avoid DHA deficiency.

PMID- 18037282
TI  - Ostreolysin enhances fruiting initiation in the oyster mushroom (Pleurotus
      ostreatus).
AB  - Fruiting initiation in mushrooms can be triggered by a variety of environmental
      and biochemical stimuli, including substances of natural or synthetic origin. In
      this work ostreolysin, a cytolytic protein specifically expressed during the
      formation of primordia and fruit bodies of Pleurotus ostreatus, was applied to
      nutrient media inoculated with mycelium of P. ostreatus, and its effects on
      mycelial growth and fructification of the mushroom studied. The addition of
      ostreolysin slightly inhibited the growth of mycelium, but strongly induced the
      formation of primordia, which appeared 10 d earlier than in control plates
      supplemented with bovine serum albumin or with the dissolving buffer alone.
      Moreover, ostreolysin stimulated the subsequent development of primordia into
      fruit bodies. However, direct involvement of this protein in the sporulation of
      the mushroom is unlikely, as it was also detected in large amounts in the non
      sporulating strain of P. ostreatus.

PMID- 18037283
TI  - Endurance or resistance training in primary care after in-patient rehabilitation
      for COPD?
AB  - Resistance (RT) and endurance training (ET) prescribed by a rehabilitation centre
      and carried out under the supervision of primary care physiotherapists after the
      completion of 4 weeks of multidisciplinary in-patient pulmonary rehabilitation
      (IPR) were compared regarding capacity to induce further health effects. After
      IPR, 40 chronic obstructive pulmonary disease (COPD) patients were allocated to
      RT or ET twice weekly for 12 weeks. Primary outcome variables were walking
      capacity (treadmill endurance time, TET; 6-min walking distance, 6MWD),
      functional status (Glittre ADL-test; Hyrim Physical Activity Questionnaire) and
      health-related quality of life (HRQOL) (St. George's Respiratory Questionnaire,
      SGRQ). Body functions variables were included as secondary outcome measures.
      HRQOL and physical activity were reinvestigated after 1 year. Median attendance
      rates were not different between RT (21, interquartile range [17;23]) and ET (22
      [18;24]). Both groups improved in TET (RT 7.7 min 95% CI {3.6;12}, ET 5.7 min
      {1.7;9.8}). 6MWD increased significantly after ET (46 m {20;72}). Functional
      status was unchanged. SGRQ tended to further improve after RT (-3.2{-7.4;1.2}),
      while ET maintained the improvement gained during IPR. Body functions measures
      changed according to training modality. After 1 year, a majority of patients in
      both groups were exercising regularly, but SGRQ was significantly better than pre
      IPR only in the RT group (-7.9{-14.3;-1.5}). We conclude that supervised RT or ET
      twice weekly sustains and improves the effects of IPR. With no large differences
      detected between the two training modalities, the choice of training may be
      guided by individual needs, patient preferences and the availability of
      equipment.

PMID- 18037284
TI  - Treatment and use of air pollution control residues from MSW incineration: an
      overview.
AB  - This work reviews strategies for the management of municipal solid waste
      incineration (MSWI) residues, particularly solid particles collected from flue
      gases. These tiny particles may be retained by different equipment, with or
      without additives (lime, activated carbon, etc.), and depending on the different
      possible combinations, their properties may vary. In industrial plants, the most
      commonly used equipment for heat recovery and the cleaning of gas emissions are:
      heat recovery devices (boiler, superheater and economiser); dry, semidry or wet
      scrubbers; electrostatic precipitators; bag filters; fabric filters, and
      cyclones. In accordance with the stringent regulations in force in developed
      countries, these residues are considered hazardous, and therefore must be treated
      before being disposed of in landfills. Nowadays, research is being conducted into
      specific applications for these residues in order to prevent landfill practices.
      There are basically two possible ways of handling these residues: landfill after
      adequate treatment or recycling as a secondary material. The different types of
      treatment may be grouped into three categories: separation processes,
      solidification/stabilization, and thermal methods. These residues generally have
      limited applications, mainly due to the fact that they tend to contain large
      quantities of soluble salts (NaCl, KCl, calcium compounds), significant amounts
      of toxic heavy metals (Pb, Zn, Cr, Cu, Ni, Cd) in forms that may easily leach
      out, and trace quantities of very toxic organic compounds (dioxin, furans). The
      most promising materials for recycling this residue are ceramics and glass
      ceramic materials. The main purpose of the present paper is to review the
      published literature in this field. A range of studies have been summarized in a
      series of tables focusing upon management strategies used in various countries,
      waste composition, treatment processes and possible applications.

PMID- 18037285
TI  - Carbon mineralization dynamics in soils amended with meat meals under laboratory
      conditions.
AB  - Meat and bone meal (MBM) is obtained from the wastes produced during slaughtering
      operations. Its high concentration of N and P makes it interesting as an organic
      fertiliser but its use in soil has been barely studied previously. In this work
      four laboratory experiments were performed to study the influence of different
      variables (MBM composition, rate of application, temperature of incubation and
      the type of soil) on C mineralization dynamics of MBM in agricultural soils. The
      total CO2-C evolved (as % of added C) after 2 weeks ranged between 10% and 20%.
      The kinetics of mineralization were rapid, with C evolved as CO2 within the first
      4 days representing more than 50% of total C mineralized. A linear correlation
      was found between the rate of application (added-C) and CO2-C evolved (r2: 0.997;
      P<0.001). A temperature coefficient (Q10) was used to assess the difference in
      biological activity at 5 degrees C intervals. Q10, which ranged from 1.0 to 2.7
      (250h), was higher for the lower temperature range (Q10 (15-20 degrees C)>Q10 (20
      25 degrees C)) and it was found to be related to the soil properties. Finally,
      the mineralization process was found to be highly dependent upon the different
      soil factors, although no simple linear correlation was found between
      mineralization and soil properties.

PMID- 18037286
TI  - Imaging of colorectal cancer: introduction.

PMID- 18037287
TI  - Pulmonary resections of single metastases from colorectal cancer.
AB  - BACKGROUND: Surgical resection is the treatment of choice of pulmonary metastases
      from colorectal cancer. We retrospectively reviewed our experience of pulmonary
      resections of single metastases from colorectal cancer, in order to document
      postoperative clinical outcome and survival. MATERIALS AND METHODS: In the years
      1997-2007, in 23 patients we performed 26 curative resections of pulmonary
      metastases from colorectal cancer (19 rectal and 7 colon; 12 males and 11
      females; mean age 64.5 years). All patients had single lung metastasis. Three of
      the 23 patients underwent re-resection of the lung for treatment of a subsequent
      lung metastasis. Interval between resection of primary tumor and diagnosis of
      lung metastasis (disease-free interval (DFI)) was >36 months in 19 patients (73%)
      and was <36 months in 7 patients (27%). In 21 patients the metastases were
      metachronous; in 2 patients metastases were synchronous with primary colorectal
      cancer. The type of lung resection was wedge resection in 18 cases (70%);
      lobectomy in 6 cases (23%); pneumonectomy in 2 cases (7%). Of the 18 wedge
      resections, 12 (66%) were done thoracoscopically. After lung metastasectomy
      patients were followed up for 5-121 months (median: 61 months). RESULTS: We had 1
      early postoperative mortality (after re-resection) from cardiac complication
      (3.8%). Postoperative morbidity (within 30 days) was observed in 7 cases (27%): 1
      pneumonia, 1 empyema, 1 arrhythmia and 4 prolonged air leaks requiring chest
      drainage >7 days. Median survival was 74 months (Kaplan-Meier). CONCLUSIONS:
      Resection of single metachronous lung metastases from colorectal cancer has low
      mortality and morbidity and in our experience it correlated with prolonged
      postoperative survival. Re-resection of the lung for treatment of subsequent
      metachronous metastases carries higher risk.

PMID- 18037288
TI  - Purification and characterization of three novel keratinolytic metalloproteases
      produced by Chryseobacterium indologenes TKU014 in a shrimp shell powder medium.
AB  - A protease-producing bacterium was isolated and identified as Chryseobacterium
      indologenes TKU014. The optimized condition for protease production was found
      when the culture was shaken at 30 degrees C for one day in 50 mL of medium
      containing 0.5% shrimp shell powder (w/v), 0.1% K(2)HPO(4), and 0.05%
      MgSO(4).7H(2)O. Three extracellular proteases (P1, P2, and P3) were purified from
      culture by DEAE-Sepharose and Phenyl Sepharose chromatography. Three enzymes all
      showed activities of keratinase and elastase with molecular weights of 56, 40, 40
      kDa, respectively. The inhibitory effect of metal chelator EDTA and Zn-specific
      chelator 1,10-phenanthroline characterized three enzymes as Zn-metalloproteases.
      Peptide mass fingerprints of P1, P2, and P3 were determined by using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Similarity search in the NCBI
      non-redundant protein sequence database revealed that three enzymes exhibited no
      significant homology to any other reported microbial peptides. Therefore, P1, P2,
      and P3 are most likely novel proteins.

PMID- 18037289
TI  - Determination of methanol in biodiesel by headspace solid phase microextraction.
AB  - A new direct gas chromatography procedure (headspace solid phase microextraction)
      was developed for the quantitative determination of methanol in biodiesel. The
      analysis was performed by exposing a carboxen-polydimethylsiloxane SPME fiber
      assembly to the headspace of the biodiesel sample. The gas chromatography used a
      HP-5 capillary column and flame ionization detection. A polynomial relationship
      was observed between the methanol concentration and its peak area. This method
      showed good reproducibility (average relative standard deviation 7.06%) and
      recovery (average recovery 100.2%).

PMID- 18037290
TI  - Isothiazolidinone inhibitors of PTP1B containing imidazoles and imidazolines.
AB  - The structure-based design and synthesis of isothiazolidinone (IZD) inhibitors of
      PTP1B containing imidazoles and imidazolines and their modification to interact
      with the B site of PTP1B are described here. The X-ray crystal structures of 3I
      and 4I complexed with PTP1B were solved and revealed the inhibitors are
      interacting extensively with the B site of the enzyme.

PMID- 18037291
TI  - Functionalization of the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)
      core.
AB  - The new BODIPY systems 1 and 2 were prepared and then used as substrates to
      explore S(N)Ar and F-B displacement reactions. Chloride was easily displaced from
      1 by a piperidine/ester, methylmagnesium bromide selectively displaced fluoride,
      and cyanide could attack both sites. System 2 readily added soft nucleophiles to
      the electrophilic carbon atoms, providing a new method for bioconjugation of
      BODIPYs to proteins while also introducing a (19)F probe.

PMID- 18037292
TI  - Role of gemcitabine in metastatic breast cancer patients: a short review.
AB  - Many active cytotoxic drugs, given according to a number of different regimens
      are approved for the treatment of metastatic breast cancer patients. However,
      these therapies have not changed the outcome of patients affected by this
      malignancy. As a consequence, the balance between chemotherapy-induced side
      effects and relief of cancer-related symptoms must be carefully considered in
      this setting. Gemcitabine is an antimetabolite that is incorporated as a
      triphosphate into DNA. As a single agent, it yields responses rates ranging from
      14% to 37% in chemotherapy-naive patients and from 12% to 30% in patients
      previously treated with anthracyclines and/or taxanes. In combination with
      paclitaxel, it produces a significantly higher response rate (41.4% vs. 26.2%),
      longer time to progression (6.1 vs. 4 months) and significantly higher overall
      survival (18.6 vs. 15.8 months) than paclitaxel alone. In addition, a phase III
      study revealed that gemcitabine plus docetaxel is as effective as capecitabine
      plus docetaxel, but causes significantly less non-haematologic toxicity. Lastly,
      in another phase III trial, progression free survival was significantly longer
      with the combination of gemcitabine plus vinorelbine than with vinorelbine alone
      (6 vs. 4 months), but without a significant difference in overall survival; the
      incidence of haematologic toxicity was higher in the group treated with combined
      therapy. Novel gemcitabine combinations are being investigated in phase II
      studies.

PMID- 18037293
TI  - Vitamin D supplementation and response to aromatase inhibitors in postmenopausal
      women with hormone-receptor positive breast cancer.

PMID- 18037294
TI  - Biomechanical investigation of ambulatory training in patients with acetabular
      dysplasia.
AB  - The purpose of this study was to investigate the effectiveness and safety of
      ambulatory training in patients with acetabular dysplasia. To achieve this, we
      studied the hip joint moment in subjects walking with laterally and horizontally
      elevated arms and changing speeds as a form of training to strengthen hip joint
      abductor muscles. We studied eight women with pre- or early stage hip disease
      (center-edge angle of Wieberg 18.5 degrees to -3.0 degrees ) and six healthy
      women. In exercise task 1 the subjects walked at a rate of 90 steps/min, with
      abduction of 90 degrees in the shoulder joint ipsilateral or contralateral to the
      affected hip joint, and either no load or a 1 kg weight in either hand. In
      exercise task 2, walking speed was changed in three stages from 60 steps/min (s
      gait), 90 steps/min (n-gait), and 120 steps/min (f-gait), with both hands
      swinging freely. Using results from a three-dimensional motion analysis system,
      the hip joint moments were calculated. In both the healthy and the acetabular
      dysplasia groups, the abduction moment of the hip joint decreased significantly
      with ipsilateral elevation and increased significantly with contralateral
      elevation. There was no significant change in hip flexion moment in either group.
      The hip extension moment decreased significantly with contralateral elevation,
      but no significant changes were seen in ipsilateral elevation. In the walking
      rate variation, the extension hip moment in fast gait was higher than in slow
      gait. It was concluded that ambulatory training with contralateral horizontal arm
      elevation may be an effective way of increasing hip joint abductor muscle
      strength. Ipsilateral arm elevation decreases gluteus medius muscle tension and
      is an effective way of ambulatory training for people with compensated
      trendelenburg gait. Variable speed walking is an effective exercise method that
      can strengthen extensor muscles. Therefore, these ambulatory training methods are
      useful for acetabular dysplasia patients.

PMID- 18037295
TI  - Partial spondylectomy: modification for lateralized malignant spinal column
      tumors of the cervical or lumbosacral spine.
AB  - Total en bloc spondylectomy is a useful technique in treating primary and
      secondary spinal malignancies, but requires extensive instrumentation to achieve
      difficult fusions, and requires extensive exposure of neurovascular structures
      that poses additional risk of nerve root and vascular injury. More limited
      resections may reduce these risks, especially in the cervical or lumbosacral
      spine. We report a technique used in two patients with lateralized primary
      vertebral tumors of the cervical or lumbosacral spine where tumor removal was
      achieved through a partial spondylectomy. The advantages of a partial
      spondylectomy included: (i) avoidance of injuring contralateral neurovascular
      structures during exposure; and (ii) supplementation of instrumentation by
      additional fixation at the level of spondylectomy. Partial spondylectomy can be
      an alternative to total en bloc spondylectomy in properly selected patients with
      lateralized encapsulated malignant spinal tumors and may be performed in the
      cervical or lumbosacral spinal regions.

PMID- 18037296
TI  - Contribution of DNA repair mechanisms to determining chemotherapy response in
      high-grade glioma.
AB  - Despite the existence of a well described, succinct pathological grading system
      for gliomas, tumour behaviour between individual patients varies widely. In
      addition, predictors of response to treatment in glioblastoma multiforme are
      lacking. The majority of chemotherapeutic agents currently employed exert their
      effect on DNA. As our understanding of DNA repair mechanisms improves and
      predictive markers are elucidated, this may allow treating clinicians to
      individualise treatment based on molecular markers. This review examines
      important DNA repair mechanisms and their application to glioblastoma multiforme.
      By improving understanding of these mechanisms, and particularly the variations
      that occur between tumours and individuals, it may be possible to adapt treatment
      to maximise effectiveness and minimise toxicity.

PMID- 18037297
TI  - Properties of flaky affinity resin with co-continuous structure.
AB  - A new type of flaky affinity resin for capture of the target proteins was
      prepared to discuss its properties compared with those of a particulate affinity
      resin. The resin prepared had totally co-continuous structure (monolith) and was
      utilized in the shape of flake. The concentration of surface amino groups for
      immobilization of ligand was determined to be 22.3 micromol/ml. Immobilizations
      of ligand such as Sulfonamide, Ketoprofen, Captopril, or Methotrexate (MTX) on
      the affinity resin were quantitatively proceeded to afford fully covered (100%)
      affinity resins. Control of the immobilization rate of affinity resin using
      Sulfonamide or Ketoprofen was successfully achieved with the calculated
      immobilization rate. The flaked shape of affinity resin (100-400 microm)
      presumably simplified affinity experimental procedures and the affinity resin
      immobilizing Sulfonamide effectively captured one of the target proteins, CAII,
      without non-specifically bound proteins. The observed properties of the flaky
      affinity resin as well as ease in handling are really useful for capture of the
      target proteins of possible rare ligands.

PMID- 18037298
TI  - Corrugoside, a new immunostimulatory alpha-galactoglycosphingolipid from the
      marine sponge Axinella corrugata.
AB  - Corrugoside (1a), a new immunostimulatory triglycosilated alpha
      galactoglycosphingolipid, was isolated from the marine sponge Axinella corrugata,
      and its structure determined by spectral analysis and chemical degradation.
      Compound 1a activated murine NKT cells in vitro, with a potency of about 2 logs
      lower than that of alphaGalCer. Four stereoisomeric glycosphingolipids (2a-2d)
      were also obtained, beta-glucosylceramides bearing unusual endoperoxide and
      allylic hydroperoxide functionalities on the sphinganine chain. They were shown
      to be photooxidation artifacts of the known glycosphingolipids 3, also present in
      the sponge. A possible role of compound 3 as a singlet oxygen scavenger to
      protect the organism from oxidative damage is proposed.

PMID- 18037300
TI  - Toward the development of chemoprevention agents (III): synthesis and anti
      inflammatory activities of a new class of 5-glycylamino-2-substituted-phenyl-1,3
      dioxacycloalkanes.
AB  - A new series of 5-glycylamino-2-substituted-phenyl-1,3-dioxacycloalkanes were
      designed and synthesized. The anti-inflammatory activities of these compounds
      were tested using the xylene-induced mouse ear edema model. Sixteen of these new
      compounds exhibited comparable or better anti-inflammatory activities than
      aspirin suggesting that they can be further developed as potential anti
      inflammatory drug leads. In addition, treatment with these anti-inflammatory
      agents did not prolong tail bleeding time in mice. The structure/activity
      relationships were also analyzed among these compounds. Considering their good
      efficacy and safety profiles, some 5-glycylamino-2-substituted-phenyl-1,3
      dioxacycloalkanes are worthy to be explored further in assessing the possible
      link between anti-inflammation and cancer prevention.

PMID- 18037299
TI  - Influence of heterocyclic and oxime-containing farnesol analogs on quorum sensing
      and pathogenicity in Candida albicans.
AB  - A series of synthetic molecules combining a geranyl backbone with a heterocyclic
      or oxime head group are quorum-sensing molecules that block the yeast to mycelium
      transition in the dimorphic fungus Candida albicans. A number of the analogs have
      an IC50 10 microM, a level of potency essentially identical to the natural quorum
      sensing signal, the sesquiterpene farnesol. Two of the most potent analogs,
      neither toxic toward healthy mice, display remarkably different effects when co
      administered with C. albicans. While neither offers protection from candidiasis,
      one analog mimics farnesol in acting as a virulence factor, whereas the other has
      no effect. The results offer the first example of highly potent synthetic fungal
      quorum-sensing molecules, and provide the first evidence for the ability to
      decouple quorum sensing and virulence.

PMID- 18037301
TI  - Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2'
      hydroxyphenyl)benzoxazole analogs of UK-1.
AB  - UK-1 is a bis(benzoxazole) natural product displaying activity against a wide
      range of human cancer cell lines. A simplified analog of UK-1, 4-carbomethoxy-2
      (2'-hydroxyphenyl)benzoxazole, was previously found to be almost as active as UK
      1 against cancer cell lines, and similar to the natural product, formed complexes
      with a variety of metal ions such as Mg2+ and Zn2+. A series of 4-substituted-2
      (2'-hydroxyphenyl)benzoxazole analogs of this 'minimal pharmacophore' of UK-1
      were prepared. The anti-cancer activity of these analogs was examined in breast
      and lung cancer cell lines. Spectrophotometric titrations in methanol were
      carried out in order to assess the ability of UK-1 and these analogs to
      coordinate with Mg2+ and Cu2+ ions. Although none of the new analogs were more
      cytotoxic than 4-carbomethoxy-2-(2'-hydroxyphenyl)benzoxazole, some analogs were
      identified that display similar cytotoxicity to this simplified UK-1 analog with
      improved water solubility. UK-1 and all of these new analogs bind Cu2+ ions
      better than Mg2+ ions, and the nature of the 4-substituent is important for the
      Mg2+ ion binding ability of these 2-(2'-hydroxyphenyl)benzoxazoles. Previous
      studies of a limited number of UK-1 analogs demonstrated a correlation between
      Mg2+ ion binding ability and cytotoxicity; however, within this series of 4
      substituted-2-(2'-hydroxyphenyl)benzoxazoles the variations in cytotoxicity do
      not correlate with either Mg2+ or Cu2+ ion binding ability. These results,
      together with recent ESI-MS studies of Cu2+-mediated DNA binding by UK-1 and
      analogs, indicate that UK-1 and analogs may exert their cytotoxic effects by
      interaction with Cu2+ or other transition metal ions, rather than Mg2+, and that
      metal ion-mediated DNA binding, rather than metal ion binding affinity, is
      important for the cytotoxic effect of these compounds. The potential role of Cu2+
      ions in the cytotoxic action of UK-1 is further supported by the observation that
      UK-1 in the presence of Cu2+ displays enhanced cytotoxicity to MCF-7 and A549
      cells when compared to UK-1 alone.

PMID- 18037302
TI  - Design of azidoproline containing gluten peptides to suppress CD4+ T-cell
      responses associated with celiac disease.
AB  - Celiac disease is an intestinal disease caused by intolerance for gluten, a
      common protein in food. A life-long gluten-free diet is the only available
      treatment. As it is well established that the interaction between proline-rich
      gluten derived peptides and the human HLA-DQ2 molecules induces immune responses
      that lead to disease development, we have now designed a series of gluten
      peptides in which proline residues were replaced by azidoprolines. These peptides
      were found to bind to HLA-DQ2 with an affinity similar to that of the natural
      gluten peptide. Moreover, some of these peptides were found to be non-immunogenic
      and block gluten induced immune responses. These can thus serve as lead compounds
      for the development of HLA-DQ2 blocker peptides.

PMID- 18037303
TI  - Serial sectioning and three-dimensional reconstruction of mouse Peyer's patch.
AB  - Peyer's patches (PPs) are typical gut-associated lymphoid tissues that are
      located along the wall of the small intestine and that serve as the major sites
      for generation of immunity to intestinal antigens. Their unique micro
      organization is crucial for the generation of the immune response. Although many
      studies have been reported on the functional anatomy of PP, most investigations
      have relied on the random sampling of these organs, a procedure that is
      insufficient for the systemic scanning of the whole tissue or organ. By combining
      a variety of methods, we have accomplished 3D reconstructions of Peyer's patch.
      The complex reconstruction procedure includes several steps. First, the PP are
      serially sectioned at a thickness of 10 microm with a cryostat; (b) the serial
      sections are stained with haematoxylin-eosin; (c) multiple images from the PP are
      acquired with an automatic microscope and stitched together with Image Pro Plus
      to generate a composite image for the whole organ; (d) the serial images are
      reconstructed with Image J, Reconstruct and 3D Studio Max. The combinational
      approaches that we present here should be of value when extrapolated to the
      reconstruction of other tissues or organs. Moreover, the 3D model that we have
      created and our stereological analysis should be extremely helpful for further in
      vivo microscopic studies of PP with respect to the immune response.

PMID- 18037304
TI  - Visualization of micromorphology of leaf epicuticular waxes of the rubber tree
      Ficus elastica by electron microscopy.
AB  - Ultrastructural aspects of leaf epicuticular waxes were investigated in Ficus
      elastica by scanning and transmission electron microscopy. Glossy leaves of the
      rubber tree were collected and subjected to different regimes of specimen
      preparation for surface observations. F. elastica leaves were hypostomatic and
      stomata were surrounded with a cuticular thickening that formed a rim. The most
      prominent epicuticular wax structures of F. elastica leaves included granules and
      platelets. Without fixation and metal coating, epicuticular wax structures could
      be discerned on the leaf surface by low-vacuum (ca. 7 Pa) scanning electron
      microscopy. In terms of delineation and retention of the structures, the
      combination of vapor fixation by glutaraldehyde and osmium tetroxide with
      subsequent gold coating provided the most satisfactory results, as evidenced by
      high resolution and sharp protrusions of epicuticular waxes. However, erosion of
      epicuticular wax edges was noted in the immersion fixed leaves, showing less
      elongated platelets, less distinct wax edges, and granule cracking. These results
      suggest that the vapor fixation procedure for demonstrating three-dimensional
      epicuticular wax structures would facilitate characterization of diverse types of
      waxes. Instances were noted where epicuticular waxes grew over neighboring
      epidermal ridges and occluded stomata. In cross sections, epicuticular waxes were
      observed above the cuticle proper and ranged approximately from 100 nm to 500 nm
      in thickness. The native leaf epicuticular waxes had many layers of different
      electron density that were oriented parallel to each other and parallel or
      perpendicular to the cuticle surface, implying strata of crystal growth. Such
      retention of native epicuticular wax structures could be achieved through the use
      of acrylic resin treated with less harsh dehydrants and mild heat polymerization,
      alleviating wax extraction during specimen preparations.

PMID- 18037305
TI  - Quantitative electron energy-loss spectroscopy (EELS) analyses of lead zirconate
      titanate.
AB  - Electron energy-loss spectroscopy (EELS) analyses have been performed on a sol
      gel deposited lead zirconate titanate film, showing that EELS can be used for
      heavy as well as light element analysis. The elemental distributions within the
      sol-gel layers are profiled using the Pb N(6,7)-edges, Zr M-edges, Ti L-edges and
      O K-edge. A multiple linear least squares fitting procedure was used to extract
      the Zr signal which overlaps with the Pb signal. Excellent qualitative
      information has been obtained on the distribution of the four elements. The non
      uniform and complementary distributions of Ti and Zr within each sol-gel
      deposited layer are observed. The metal:oxygen elemental ratios are quantified
      using experimental standards of PbTiO(3), PbZrO(3), ZrO(2) and TiO(2) to provide
      relevant cross-section ratios. The quantitative results obtained for Ti/O and
      Pb/O are very good but the Zr/O results are less accurate. Methods of further
      improving the results are discussed.

PMID- 18037306
TI  - Isolation and characterization of multiple abundant lipid transfer protein
      isoforms in developing sesame (Sesamum indicum L.) seeds.
AB  - Sesame (Sesamum indicum) is an important oilseed crop; approximately 50% of the
      seed dry weight is storage oil. In a previous report, developing sesame seed
      expressed sequence tags (ESTs) revealed that ESTs encoding lipid transfer protein
      (LTPs) were one of the most abundant groups of sesame ESTs. LTP functions in the
      transfer of wax or cutin monomers and in the defense response against pathogen
      attack. To study the biological role of the abundant LTP isoforms in developing
      seeds, 122 ESTs out of 3328 sesame ESTs were analyzed against Arabidopsis and
      rice proteome databases. LTP fraction, which was partially purified from
      developing sesame seeds, actively transferred fluorescent phospholipids and bound
      to fatty acids. Full-length cDNAs of five out of 21 LTP isoforms were isolated
      and named SiLTP1-SiLTP5. The predicted amino acid sequences of the five SiLTPs
      harbor typical characteristics of LTPs, including conserved arrangement of
      cysteine residues. Northern blot analysis revealed that the five SiLTP isoforms
      were most abundantly expressed in developing seeds, but were also detected in
      flower tissues. Also, SiLTP3 and SiLTP4 transcripts were expressed in leaves and
      seed-pot walls, respectively. In addition, SiLTP2 and SiLTP4 transcripts were
      significantly induced in 6-day-old sesame seedlings by application of NaCl,
      mannitol, and abscisic acid (ABA). Transient expression of green fluorescent
      protein (GFP)-fusion constructs in Arabidopsis protoplasts revealed that SiLTP1
      and SiLTP2 were secreted by different pathways. Taken together, the abundant LTPs
      in developing sesame seeds are involved in lipid transfer into the extracellular
      matrix. Possible biological roles of SiLTPs related to organ-specific expression
      and abiotic stresses are discussed.

PMID- 18037308
TI  - Differences among lower leg muscles in long-term activity during ambulatory
      condition without any moderate to high intensity exercise.
AB  - The present study aimed to investigate differences among the soleus (Sol), medial
      gastrocnemius (MG) and tibialis anterior (TA) in electromyogram (EMG) activities
      during ambulatory condition without any moderate to high intensity exercise. From
      10:00 to 17:00, seven healthy graduate students participated in EMG recordings,
      which included the measurements during maximal voluntary efforts. During the long
      term EMG recoding, the subjects were instructed to perform normal daily routines,
      including desk work and the attendance of lectures. EMG signals from the three
      muscles were averaged every 0.1s and expressed as a percentage (%MVE) of those
      obtained with maximal voluntary efforts, averaged over 1s. An EMG burst which had
      an amplitude >2%MVE and a duration >0.1s was defined as muscular activity.
      Regardless of muscles examined, the amplitude of the greater part of all bursts
      observed over the recording time was less than 30%MVE. The summed duration of all
      bursts over the recording time was significantly greater in Sol than in MG and
      TA, without a significant difference in the summed number of all bursts among the
      three muscles. The percentage of the summed duration of bursts at less than
      10%MVE to that over the recording time was significantly higher in Sol and TA
      than in MG, but the corresponding value at 20< or =%MVE<30 was lower. Thus, EMG
      responses during ambulatory condition without any moderate to high intensity
      exercise differed among the three muscles, even between synergists: Sol was
      predominantly activated with low burst amplitudes as compared to MG.

PMID- 18037309
TI  - Immediate effects of co-contraction training on motor control of the trunk
      muscles in people with recurrent low back pain.
AB  - Although deficits in the activation of abdominal muscles are present in people
      with low back pain (LBP), this can be modified with motor training. Training of
      deep abdominal muscles in isolation from the other trunk muscles, as an initial
      phase of training, has been shown to improve the timing of activation of the
      trained muscles, and reduce symptoms and recurrence of LBP. The aim of this study
      was to determine if training of the trunk muscles in a non-isolated manner can
      restore motor control of these muscles in people with LBP. Ten subjects with non
      specific LBP performed a single session of training that involved three tasks:
      "abdominal curl up", "side bridge" and "birdog". Electromyographic activity (EMG)
      of trunk and deltoid muscles was recorded with fine-wire and surface electrodes
      during rapid arm movements and walking, before and immediately following the
      intervention. Onset of trunk muscle EMG relative to that of the prime mover
      (deltoid) during arm movements and the mean, standard deviation (SD) and
      coefficient of variation of abdominal muscle EMG during walking were calculated.
      There was no significant change in the times of onset of trunk muscle EMG during
      arm movements nor was there any change in the variability of EMG of the abdominal
      muscles during walking. However, the mean amplitude and SD of abdominal EMG was
      reduced during walking after training. The results of this study suggest that
      unlike isolated voluntary training, co-contraction training of the trunk muscles
      does not restore the motor control of the deep abdominal muscles in people with
      LBP after a single session of training.

PMID- 18037310
TI  - Construction of a 3D probabilistic atlas of human cortical structures.
AB  - We describe the construction of a digital brain atlas composed of data from
      manually delineated MRI data. A total of 56 structures were labeled in MRI of 40
      healthy, normal volunteers. This labeling was performed according to a set of
      protocols developed for this project. Pairs of raters were assigned to each
      structure and trained on the protocol for that structure. Each rater pair was
      tested for concordance on 6 of the 40 brains; once they had achieved reliability
      standards, they divided the task of delineating the remaining 34 brains. The data
      were then spatially normalized to well-known templates using 3 popular
      algorithms: AIR5.2.5's nonlinear warp (Woods et al., 1998) paired with the
      ICBM452 Warp 5 atlas (Rex et al., 2003), FSL's FLIRT (Smith et al., 2004) was
      paired with its own template, a skull-stripped version of the ICBM152 T1 average;
      and SPM5's unified segmentation method (Ashburner and Friston, 2005) was paired
      with its canonical brain, the whole head ICBM152 T1 average. We thus produced 3
      variants of our atlas, where each was constructed from 40 representative samples
      of a data processing stream that one might use for analysis. For each
      normalization algorithm, the individual structure delineations were then
      resampled according to the computed transformations. We next computed averages at
      each voxel location to estimate the probability of that voxel belonging to each
      of the 56 structures. Each version of the atlas contains, for every voxel,
      probability densities for each region, thus providing a resource for automated
      probabilistic labeling of external data types registered into standard spaces; we
      also computed average intensity images and tissue density maps based on the three
      methods and target spaces. These atlases will serve as a resource for diverse
      applications including meta-analysis of functional and structural imaging data
      and other bioinformatics applications where display of arbitrary labels in
      probabilistically defined anatomic space will facilitate both knowledge-based
      development and visualization of findings from multiple disciplines.

PMID- 18037311
TI  - Who was the first to use the term Pickwickian in connection with sleepy patients?
      History of sleep apnoea syndrome.
AB  - The symptoms and characteristics of sleep apnoea syndrome--excessive daytime
      sleepiness, loud snoring, restless and non-restorative sleep--are so impressive
      that it is difficult to understand why its recognition was delayed until the
      1970s. The Centennial book of the American Thoracic Society credited Sidney
      Burwell for the discovery of Obstructive Sleep Apnoea Syndrome. This is only one
      of the many mistakes and misattributions regarding the history of sleep apnoea
      syndrome. The earliest descriptions of patients who presumably suffered from
      sleep apnoea were made in the 19th century. The term "Pickwickian" in connection
      with sleepy patients was introduced in 1889. The first electrophysiological sleep
      recordings of Pickwickian patients and the understanding of the syndrome as
      disordered breathing in sleep, were made during the late 1950s and 1960s. Its
      recognition as a public health problem was facilitated by Young et al.'s [Young
      T, Palta M, Dempsey J, et al. The occurrence of sleep-disordered breathing among
      middle-aged adults. N Engl J Med 1993;328:1230-5] seminal paper documenting the
      prevalence of the syndrome in the general population, and by the accumulated
      evidence that the syndrome is a major cardiovascular risk factor. Bibliometric
      analysis of the literature on sleep apnoea reveals that future research will
      focus on the long-term outcomes of the syndrome, on the effects of treatment, and
      on the underlying mechanisms linking it with cardiovascular morbidity.

PMID- 18037312
TI  - Characterisation of the acute and reversible airway inflammation induced by
      cadmium chloride inhalation in healthy dogs and evaluation of the effects of
      salbutamol and prednisolone.
AB  - The aims of this study were firstly to characterise a model of subclinical and
      reversible bronchial inflammation induced by cadmium chloride inhalation in
      healthy dogs and then to examine the effect of prednisolone or salbutamol
      treatment on the resulting bronchitis. The model characterisation and the effects
      of treatment were studied using clinical symptoms, haematology, thoracic
      radiography, bronchoscopy and bronchoalveolar lavage, barometric whole-body
      plethysmography and histamine broncho-provocation tests. In addition, the
      activity of matrix metalloproteinases (MMP)-2 and -9 were determined in serum and
      bronchoalveolar lavage fluid (BALF). Cadmium inhalation induced: (1) a transient
      bronchial inflammation, dominated by neutrophils; (2) a neutrophilia of the blood
      that persisted for up to 4 weeks; (3) a transient increased bronchial reactivity,
      and (4) a significant increase in MMP-9 activity in the BALF. Prednisolone
      treatment reduced the influx of inflammatory cells into the BALF, but not
      significantly, had no effect on pulmonary function, and did not reduce of airway
      hypersensitivity. Salbutamol had almost no effect on any of the parameters
      investigated.

PMID- 18037313
TI  - In vivo lung morphometry with hyperpolarized 3He diffusion MRI: theoretical
      background.
AB  - MRI-based study of (3)He gas diffusion in lungs may provide important information
      on lung microstructure. Lung acinar airways can be described in terms of
      cylinders covered with alveolar sleeve [Haefeli-Bleuer, Weibel, Anat. Rec. 220
      (1988) 401]. For relatively short diffusion times (on the order of a few ms) this
      geometry allows description of the (3)He diffusion attenuated MR signal in lungs
      in terms of two diffusion coefficients-longitudinal (D(L)) and transverse (D(T))
      with respect to the individual acinar airway axis [Yablonskiy et al., PNAS 99
      (2002) 3111]. In this paper, empirical relationships between D(L) and D(T) and
      the geometrical parameters of airways and alveoli are found by means of computer
      Monte Carlo simulations. The effects of non-Gaussian signal behavior (dependence
      of D(L) and D(T) on b-value) are also taken into account. The results obtained
      are quantitatively valid in the physiologically important range of airway
      parameters characteristic of healthy lungs and lungs with mild emphysema. In
      lungs with advanced emphysema, the results provide only "apparent"
      characteristics but still could potentially be used to evaluate emphysema
      progression. This creates a basis for in vivo lung morphometry-evaluation of the
      geometrical parameters of acinar airways from hyperpolarized (3)He diffusion MRI,
      despite the airways being too small to be resolved by direct imaging. These
      results also predict a rather substantial dependence of (3)He ADC on the
      experimentally-controllable diffusion time, Delta. If Delta is decreased from 3
      ms to 1 ms, the ADC in normal human lungs may increase by almost 50%. This effect
      should be taken into account when comparing experimental data obtained with
      different pulse sequences.

PMID- 18037314
TI  - Electron spin relaxation enhancement measurements of interspin distances in
      human, porcine, and Rhodobacter electron transfer flavoprotein-ubiquinone
      oxidoreductase (ETF-QO).
AB  - Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a membrane
      bound electron transfer protein that links primary flavoprotein dehydrogenases
      with the main respiratory chain. Human, porcine, and Rhodobacter sphaeroides ETF
      QO each contain a single [4Fe-4S](2+,1+) cluster and one equivalent of FAD, which
      are diamagnetic in the isolated enzyme and become paramagnetic on reduction with
      the enzymatic electron donor or with dithionite. The anionic flavin semiquinone
      can be reduced further to diamagnetic hydroquinone. The redox potentials for the
      three redox couples are so similar that it is not possible to poise the proteins
      in a state where both the [4Fe-4S](+) cluster and the flavoquinone are fully in
      the paramagnetic form. Inversion recovery was used to measure the electron spin
      lattice relaxation rates for the [4Fe-4S](+) between 8 and 18K and for
      semiquinone between 25 and 65K. At higher temperatures the spin-lattice
      relaxation rates for the [4Fe-4S](+) were calculated from the temperature
      dependent contributions to the continuous wave linewidths. Although mixtures of
      the redox states are present, it was possible to analyze the enhancement of the
      electron spin relaxation of the FAD semiquinone signal due to dipolar interaction
      with the more rapidly relaxing [4Fe-4S](+) and obtain point-dipole interspin
      distances of 18.6+/-1A for the three proteins. The point-dipole distances are
      within experimental uncertainty of the value calculated based on the crystal
      structure of porcine ETF-QO when spin delocalization is taken into account. The
      results demonstrate that electron spin relaxation enhancement can be used to
      measure distances in redox poised proteins even when several redox states are
      present.

PMID- 18037315
TI  - In silico screening against wild-type and mutant Plasmodium falciparum
      dihydrofolate reductase.
AB  - Modeling studies were performed on known inhibitors of wild-type as well as
      quadruple mutant Plasmodium falciparum dihydrofolate reductase (DHFR). GOLD was
      used to dock 31 pyrimethamine derivatives into the active site of DHFR obtained
      from the X-ray crystal structures 1J3I.pdb and 1J3K.pdb. Predicted binding
      affinities from a scoring function were analyzed and evaluated in order to
      develop criteria for selecting compounds having a greater chance of activity
      versus wild-type and resistant strains of P. falciparum for future high
      throughput screening experiments.

PMID- 18037316
TI  - Influence of oral contraceptive use on growth hormone in vivo bioactivity
      following resistance exercise: responses of molecular mass variants.
AB  - The purpose was to examine effects of oral contraceptive (OC) use on plasma
      growth hormone (GH) responses to heavy resistance exercise. Sixty untrained women
      were placed into one of two groups: currently using OC (Ortho Tri-Cyclen) (n=25;
      mean+/-SD: 24.5+/-4.2y, 160.4+/-7.1cm, 64.1+/-11.3kg) or not currently using OC
      (NOC) (n=35; 23.6+/-4.6y, 165.9+/-6.0cm, 65.7+/-10.3kg). Participants performed
      an acute heavy resistance exercise test (AHRET; six sets of 10 repetition squats;
      2min rest between sets) during days 2-4 of the follicular phase (NOC group) or of
      inactive oral contraceptive intake (OC group). Plasma was obtained before and
      immediately after AHRET and subsequently fractionated based on apparent molecular
      weight (>60kD, 30-60kD, and <30kD). GH was determined in unfractionated plasma
      and each plasma fraction using 4 methods: (1) Nichols Institute Diagnostics
      immunoradiometric assay (Nichols), (2) National Institute of Diabetes and
      Digestive Kidney Diseases (NIDDK) competitive radioimmunoassay, (3) DSL
      immunofunctional enzyme-linked immunoabsorbent assay (IFA) and (4) rat tibial
      line bioassay. GH increased (P<0.05) in all fractions post-AHRET for the Nichols,
      NIDDK, and IFA. The OC group displayed higher resting GH for the NIDDK, and
      higher exercise-induced GH for the IFA, Nichols, and NIDDK in unfractionated
      plasma and >60kD subfraction compared to NOC group. No differences were observed
      for the tibial line bioassay. OC use augmented immunological GH response to AHRET
      in unfractionated plasma and >60kD molecular weight subfraction. However, OC use
      only increased biological activity of GH in one of two bioassays. These data
      demonstrated that GH concentrations at rest and following exercise are assay
      dependent.

PMID- 18037317
TI  - Females with Fabry disease frequently have major organ involvement: lessons from
      the Fabry Registry.
AB  - Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha
      galactosidase A deficiency. The Fabry Registry is a global clinical effort to
      collect longitudinal data on FD. In the past, most "carrier" females were usually
      thought to be clinically unaffected. A systematic effort has been made to enroll
      all FD females, regardless of symptomology. Of the 1077 enrolled females in the
      Registry, 69.4% had symptoms and signs of FD. The median age at symptom onset
      among females was 13 years, and even though 84.1% had a positive family history,
      the diagnosis was not made until a median age of 31 years. Twenty percent
      experienced major cerebrovascular, cardiac, or renal events, at a median age of
      46 years. Among adult females with estimated glomerular filtration rate (eGFR)
      data (N=638), 62.5% had an eGFR <90 ml/min/1.73 m2 and 19.0% had eGFR <60
      ml/min/1.73 m2. Proteinuria 300 mg/day was present in 39.0% of females, and 22.2%
      had >1 gram/day. Quality of life (QoL), as measured by the SF-36((R)) survey, was
      impaired at a later age than in males, but both genders experience significantly
      impaired QoL from the third decade of life onward. Thus, females with FD have a
      significant risk for major organ involvement and decreased QoL. Females should be
      regularly monitored for signs and symptoms of FD, and considered for enzyme
      replacement therapy.

PMID- 18037318
TI  - [Microtitration of anti-RH1 antibodies: interest in the follow-up of pregnant
      women].
AB  - The proposal for a 300 microg anti-RH1 injection at 28 GW by RH:-1 pregnant women
      complicates the interpretation of the screening for alloantibodies during
      pregnancy; to distinguish an alloantibody from a passive one is nevertheless
      important for the care of the patients. Testing a technique allowing this
      distinction seems thus necessary. MATERIAL AND METHODS: The technique of
      microtitration of anti- RH1 antibodies is an indirect antiglobulin test. Two
      hundred specimens were tested in comparison with a standard prepared from a
      national anti- RH1 standard. If the anti- RH1 concentration measured is lower or
      equal to the expected concentration, there is a passive antibody. If the
      concentration is largely higher, we can suspect an allo-immunization. RESULTS:
      With this technique, 38 alloanti- RH1 and 112 passive anti- RH1 antibodies were
      confirmed. Twenty-five diagnosis were modified: seven alloanti- RH1 initially
      labeled passive and 18 passive anti- RH1 previously considered as alloantibodies.
      15 cases can not be concluded, because the blood sample was taking away too early
      after the injection, and 10 cases are on standby, waiting for a control.
      DISCUSSION: The microtitration is an important exam in the follow-up of the RH:-1
      pregnant women when an anti-RH1 antibody is found. This exam should be offered
      each time we have no information about the anti-D injection, or when an
      incoherent reaction compared to the presumed date of injection is observed.

PMID- 18037319
TI  - Recommendations of the French Society for Rheumatology regarding TNFalpha
      antagonist therapy in patients with rheumatoid arthritis.
AB  - OBJECTIVES: To update French Society for Rheumatology guidelines regarding the
      use of TNFalpha antagonists for treating patients with rheumatoid arthritis (RA).
      METHODS: Existing guidelines were updated using the AGREE instrument. Items that
      required updating were selected by a task force, the relevant literature was
      critically appraised, and new wording was suggested by a limited committee of
      experts then validated by the task force and subsequently by a panel of external
      reviewers. The three-topic structure of the recommendations (indication,
      initiation, and adjustment) and the final algorithm format were maintained.
      RESULTS: Of the 12 items, five were selected for updating; one pertained to the
      indication for treatment with TNFalpha antagonists, two to treatment initiation,
      and two to treatment adjustment. Of the four initially recommended criteria for
      determining that TNFalpha antagonist therapy is indicated, the first three were
      left unchanged (confirmed diagnosis of RA; active disease for more than 1month
      with objective evidence of inflammation or progressive structural damage, or
      dependency on glucocorticoid therapy, or progressive radiographic damage; and
      failure to respond adequately to methotrexate - or another agent when
      methotrexate is contraindicated - in the optimal tolerated dosage). The fourth
      and last criterion was modified as follows: co-morbidities should be evaluated in
      order to distinguish absolute contraindications from relative contraindications
      that require referral to a specialist. Of the four initial recommendations about
      TNFalpha antagonist initiation, the first and fourth were left unchanged (a
      workup should be performed prior to treatment initiation, and the patient should
      receive regular standardized follow-up); the second and third recommendations
      were modified as follows: there is no evidence that one TNFalpha antagonist is
      more effective than the others, and concomitant methotrexate therapy is generally
      advisable, regardless of the TNFalpha antagonist used. Of the four
      recommendations about treatment adjustment, the first two were modified as
      follows: the goal of treatment is to achieve the EULAR response criteria or
      better; and in non-responders, the dosage or dosing interval can be modified when
      infliximab is used, methotrexate should be added when the TNFalpha antagonist is
      used alone, and in all other situations the patient should be switched to a
      different TNFalpha antagonist. The other two recommendations about treatment
      adjustment were left unchanged (patients who fail to tolerate one TNFalpha
      antagonist can be switched to another TNFalpha antagonist if allowed by the
      nature of the adverse event; and when a remission is achieved, reduction or
      discontinuation of symptomatic drugs - most notably glucocorticoids - is
      appropriate, followed in the event of a prolonged remission by changes in the
      dosage and/or dosing interval of the TNFalpha antagonist or concomitant disease
      modifying drug). CONCLUSION: These recommendations are designed to help
      practitioners optimize the use of TNFalpha antagonists in patients with RA seen
      in everyday practice. They do not constitute regulations.

PMID- 18037320
TI  - [How I perform...uterine artery ligation for postpartum haemorrhage].

PMID- 18037321
TI  - [How I perform...hypogastric artery ligation for postpartum haemorrhage].

PMID- 18037322
TI  - [Surgical management of peripartum hemorrhage: a retrospective study].
AB  - OBJECTIVE: Peripartum haemorrhage is an obstetrical emergency and requests a life
      saving procedure. The purpose of this study is to describe our experience with
      the surgical management of peripartum haemorrhage. PATIENTS AND METHODS: We
      performed a retrospective study including 16 patients who necessitated a surgical
      management of peripartum haemorrhage (artery ligations, uterine compression
      and/or emergency peripartum hysterectomy) between 1985 and 2007. RESULTS: The
      incidence of surgical management of peripartum haemorrhage was 0.047%.
      Conservative surgical management consisted in uterine compression sutures in
      three cases. Artery ligations were performed without success in seven patients;
      only one case of isolated utero-ovarian artery ligations was effective. An
      emergency peripartum hysterectomy was necessary in 12 cases. Uterine atony was
      the principal etiologic factor (43.8% of cases). There were no significant
      perioperative complications. No maternal death was reported. DISCUSSION AND
      CONCLUSION: In cases of non life-saving procedure, medical treatment and uterine
      arteries embolisation are often sufficient. Uterine compression suturing
      techniques are interesting alternatives and uterine arteries ligations can always
      be performed before hysterectomy. In cases of failure of conservative treatment,
      the emergency peripartum hysterectomy must be performed. Then, the choice
      concerning the surgical technique for the management of peripartum haemorrhage
      may be adapted to the patient, the centre and the obstetrical team.

PMID- 18037324
TI  - [Prolegomena before any psychoanalytical approach to endometriosis. Reply to the
      association EndoFrance about the article by J.-M. Louka].

PMID- 18037325
TI  - [Fifteen practical questions concerning gestational diabetes. Reply to O. Picone
      about the article by J.-C. Clay et al].

PMID- 18037326
TI  - [Prolegomena before any psychoanalytical approach to endometriosis. Reply to Ph.
      Collinet about the article by J.-M. Louka].

PMID- 18037327
TI  - [Screening for aneuploidies in twins].
AB  - The incidence of twins has dramatically increased in the last two decades. The
      theorical risk of aneuploidy is higher than in singletons. Screening for
      aneuploidies should be offered in all twin pregnancies. This review examines the
      current methods and evidence regarding screening for fetal aneuploidies in twin
      pregnancies.

PMID- 18037328
TI  - Allele frequencies of a SNP and a 27-bp deletion that are the determinant of
      earwax type in the ABCC11 gene.
AB  - Allele frequencies for a SNP (rs17822931) and a 27-bp deletion that are the
      determinant of earwax type in the ABCC11 gene were investigated in seven
      Japanese, one Korean, and one German populations. The SNP will be useful as one
      of ancestry information markers, because it showed marked difference in
      frequencies between Asian and European populations.

PMID- 18037329
TI  - Pulmonary thromboembolism: overview and update from medicolegal aspects.
AB  - Pulmonary thromboembolism (PTE) has recently been the focus of research, with
      special attention to its clinical and medicolegal aspects. Deep vein thrombosis
      (DVT) is an important embolic source of PTE. We review the epidemiology, autopsy
      findings, pathophysiology, and clinical issues related to PTE and DVT in Japan
      based on our autopsy cases at the Tokyo Medical Examiner's Office.

PMID- 18037330
TI  - Scuba-diving related deaths in Okinawa, Japan, from 1982 to 2007.
AB  - We reviewed the autopsies of scuba-diving related deaths (SDRDs) that were
      collected from April 1982 until March 2007. In the period under consideration, a
      total of 40 SDRDs were registered, out of which 34 were males and 6 females. Ages
      ranged from 19 to 65 years, with the average of 41.5 years (SD=12.9). Divers over
      the age of 40 accounted for 60% of all fatalities. The major cause of death was
      drowning (62.5%), followed by disease (28.5%). The average age for drowning and
      disease-related deaths was 38.6 (SD=12.8) and 48.7 years (SD=10.1), respectively.
      Of the 40 fatalities, 24 were beginners who had little or no experience. In this
      study, we compared SDRDs in the first term, from April 1982 to March 1995, and in
      the second term, from April 1995 to March 2007. The average age in the first and
      second terms was 35.4 and 45.2 years, respectively; the average age for the
      second term was 10 years older than the first. Of those in the first term, 13.3%,
      and of those in the second term, 40.0%, died from complications arising from
      already existing conditions. This study revealed that the onset of diseases
      during diving frequently causes fatal accidents, especially for older divers.

PMID- 18037331
TI  - Alteration of load sharing of anterior cervical implants with change in cervical
      sagittal alignment.
AB  - Anterior cervical discectomy and fusion (ACDF) is often supplemented with the
      application of an anterior plate to improve the stability of the fusion segment.
      While plate design has been shown to influence stress shielding of the graft,
      little is known about how the kyphotic alignment of a fused cervical segment
      affects the load sharing between the anterior plate and the osteoligamentous
      structures of the spine. The aim of this study was to characterize load sharing
      between an anterior plate and the osteoligamentous structures of the cervical
      motion segments in kyphotic versus normal lordotic alignment following single
      level ACDF using fresh ovine cervical spines (C3-C6). The loading protocol
      involved preloading the spine with a 20 N compressive force and applying quasi
      static moments (up to 2.1 Nm) in the sagittal plane to simulate flexion and
      extension. Stiffness of the fusion segment was measured from the moment-rotation
      plot. Normal lordotic alignment was replicated by insertion of a fibular
      allograft 2 mm taller than the interbody space. Kyphotic alignment was simulated
      by removing the graft and reapplying a shorter anterior cervical plate. The
      average segmental sagittal angulation at C4-C5 was 5.2+/-1.6 degrees of lordosis
      for the normal lordotic group and 6.8+/-2.3 degrees of kyphosis for the kyphotic
      group. With flexion, the plate shared 52.8% of the applied load in the normal
      lordotic group, and 70.1% in the kyphotic group (p<0.03). In extension, the
      amount of load-share by the plate in the normal lordotic group was comparable to
      that of the kyphotic group (52.7% vs. 40.7%, p=0.16). This study shows that
      kyphotic alignment of the cervical fusion segment increases the load sharing of
      the anterior plate under flexion loading.

PMID- 18037332
TI  - Determinants of restorative experiences in everyday favorite places.
AB  - The study was based on the answers to a mailed questionnaire of a simple random
      sample of respondents from two cities (Helsinki, Tampere) in Finland. Ten
      determinants of restorative experiences in favorite places (<or = 15 km from
      home; n=1089) were effective. These determinants included "immediate" use of the
      favorite place (duration and frequency), personal background of nature
      experiences (nature orientedness, nature hobbies, childhood nature experiences),
      and situational factors in life, which were related to stress (hassles at work
      and with money, satisfaction with life) and to social relations (uplifts of
      social relations, visiting alone vs. in company). Different variables were
      associated with restorative experiences in different favorite settings
      (extensively managed nature areas, built-up green spaces, waterside environments,
      exercise and activity/hobby areas, and indoor and outdoor urban areas). The
      concept of "favorite place prescriptions" is introduced as an analogy to
      "exercise prescriptions" in primary healthcare.

PMID- 18037333
TI  - PDZ-domain containing-2 (PDZD2) is a novel factor that affects the growth and
      differentiation of human fetal pancreatic progenitor cells.
AB  - Early-trimester human fetal pancreas is a promising potential source of
      pancreatic progenitor cells. However, the ethical controversy associated with the
      source of these cells, and technical difficulties associated with their
      differentiation into insulin-producing cells have limited both their availability
      and utility. This study aimed to characterize a population of pancreatic
      progenitor cells (PPCs) isolated from human fetus and describe the effects of a
      novel factor, PDZ-domain containing-2 (PDZD2), and its secreted form (sPDZD2), on
      PPC proliferation and differentiation. In particular, we examined and
      characterized the expression of several stem cell (nestin, ABCG2, c-kit), growth
      and differentiation markers (GLP-1R, c-met, erbB1), and PDZD2 in PPCs by RT-PCR,
      Western blot, and immunocytochemistry. We also examined the effects of sPDZD2 on
      PPC proliferation and differentiation by examining BrdU incorporation, MTT, cell
      number, and real-time PCR as well as ELISA. PPCs were isolated, cultured and
      characterized from human fetal pancreas. PDZD2 and sPDZD2 were detected at high
      levels in both human fetal pancreas and in PPCs. sPDZD2 acted as a potent mitogen
      on PPCs, and inhibited the differentiation of PPC-derived islet-like cell
      clusters (ICCs), evidenced by the downregulation of Isl-1, Pdx-1, and insulin
      mRNA levels. sPDZD2 treatment also reduced levels of C-peptide in ICCs. These
      results show that a novel pancreatic developmental factor, PDZD2, is sufficient
      to promote the proliferation of human fetal PPCs while limiting differentiation
      of ICCs into islet/endocrine cells. Findings from this study will contribute to
      the development of improved methods for islet transplantation therapy in the
      treatment of diabetes.

PMID- 18037334
TI  - Site-directed mutagenesis of Arginine282 suggests how protons and peptides are co
      transported by rabbit PepT1.
AB  - The mammalian proton-coupled peptide transporter PepT1 is the major route of
      uptake for dietary nitrogen, as well as the oral absorption of a number of drugs,
      including beta-lactam antibiotics and angiotensin-converting enzyme inhibitors.
      Here we have used site-directed mutagenesis to investigate further the role of
      conserved charged residues in transmembrane domains. Mutation of rabbit PepT1
      arginine282 (R282, transmembrane domain 7) to a positive (R282K) or
      physiologically titratable residue (R282H), resulted in a transporter with wild
      type characteristics when expressed in Xenopus laevis oocytes. Neutral (R282A,
      R282Q) or negatively charged (R282D, R282E) substitutions gave a transporter that
      was not stimulated by external acidification (reducing pH(out) from 7.4 to 5.5)
      but transported at the same rate as the wild-type maximal rate (pH(out) 5.5);
      however, only the R282E mutation was unable to concentrate substrate above the
      extracellular level. All of the R282 mutants showed trans-stimulation of efflux
      comparable to the wild-type, except R282E-PepT1 which was faster. A conserved
      negatively charged residue, aspartate341 (D341) in transmembrane domain 8 was
      implicated in forming a charge pair with R282, as R282E/D341R- and R282D/D341R
      PepT1 had wild-type transporter characteristics. Despite their differences in
      ability to accumulate substrate, both R282E- and R282D-PepT1 showed an increased
      charge:peptide stoichiometry over the wild-type 1:1 ratio for the neutral
      dipeptide Gly-l-Gln, measured using two-electrode voltage clamp. This extra
      charge movement was linked to substrate transport, as 4-aminobenzoic acid, which
      binds but is not translocated, did not induce membrane potential depolarisation
      in R282E-expressing oocytes. A model is proposed for the substrate
      binding/translocation process in PepT1.

PMID- 18037335
TI  - Origin of periendothelial cells in microvessels derived from human microvascular
      endothelial cells.
AB  - In microvessels, periendothelial cells expressing alpha smooth muscle actin
      (alphaSMA) interact with the endothelial cells and are essential for vessel
      maturation and stabilization. In adult tissues, the cellular origin of the
      periendothelial cells is still not clear, in particular in humans. To determine
      the origin of human periendothelial cells, we used a recently developed 3D co
      culture system that mimics human skin connective tissue. This system is composed
      of normal human dermal fibroblasts (NHDF), human dermal microvascular endothelial
      cells (HMEC-1), and a collagen matrix. In this system, "microvessels" composed of
      an endothelial lumen associated with periendothelial cells develop. Using this co
      culture system, we (i) labelled fibroblasts with the vital dye CFDA-SE, cultured
      them with unlabelled endothelial cells, and observed that only endothelium
      associated CFDA-SE-labelled cells express alphaSMA; (ii) infected endothelial
      cells with a retrovirus stably expressing eGFP, cultured them with unlabelled
      fibroblasts, and observed that cells expressing alphaSMA did not co-express eGFP,
      but were associated with the eGFP-expressing endothelial cells of the
      microvessels. Together, these results indicate that periendothelial cells arise
      by differentiation from fibroblasts and that they require interaction with
      endothelial cells to do so.

PMID- 18037336
TI  - Diabetes induces changes of catecholamines in primary mesangial cells.
AB  - Diabetes mellitus is a frequent cause of kidney function damage with diabetic
      nephropathy being predominantly related to glomerular dysfunction. Diabetes is
      capable of interfering with distinct hormonal systems, as well as catecholamine
      metabolism. Since mesangial cells, the major constituent of renal glomerulus,
      constitute a potential site for catecholamine production, the present study was
      carried out to investigate alterations in catecholamine metabolism in cultured
      mesangial cells from the nonobese diabetic mouse, a well-established model for
      type I diabetes. We evaluated mesangial cells from normoglycemic and
      hyperglycemic nonobese diabetic mice, as well as cells from normoglycemic Swiss
      mice as control. Mesangial cells from normoglycemic mice presented similar
      profiles concerning all determinations. However, cells isolated from
      hyperglycemic animals presented increased dopamine and norepinephrine
      production/secretion. Among the studied mechanisms, we observed an upregulation
      of tyrosine hydroxylase expression accompanied by increased tetrahydrobiopterin
      consumption, the tyrosine hydroxylase enzymatic cofactor. However, this increase
      in synthetic pathways was followed by decreased monoamine oxidase activity, which
      corresponds to the major metabolic pathway of catecholamines in mesangial cells.
      In addition, whole kidney homogenates from diabetic animals also presented
      increased dopamine and norepinephrine levels when compared to normoglycemic
      animals. Thus, our results suggest that diabetes alters catecholamine production
      by interfering with both synthesizing and degrading enzymes, suggesting a
      possible role of catecholamine in the pathogenesis of acute and chronic renal
      complications of diabetes mellitus.

PMID- 18037337
TI  - Forkhead box protein 3: essential immune regulatory role.
AB  - CD4+CD25+ regulatory T (Treg) cells play a crucial role in maintaining self
      tolerance and preventing autoimmune disease. The transcription factor forkhead
      box protein 3 (Foxp3) has been identified as a molecular marker for Treg cells.
      Foxp3 is highly expressed in lymphoid tissue and several signalling pathways
      influence its expression. It plays an essential role in the development and
      function of Treg cells. Mutations in Foxp3 are responsible for the scurfy (sf)
      mutant mouse, and for autoimmune human diseases including the X-linked fatal
      "immune dysregulation, polyendocrinopathy, enteropathy, X-linked" (IPEX),
      autoimmune colitis and rheumatoid arthritis. Recent studies have also revealed an
      important and novel anti-atherogenic role for Treg cells and consequently for
      Foxp3. These data open up potential novel therapeutic avenues for the management
      of atherosclerosis.

PMID- 18037338
TI  - Characterization of mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine in
      an industrial Corynebacterium glutamicum strain.
AB  - Mutations induced by classical whole-cell mutagenesis using N-methyl-N'-nitro-N
      nitrosoguanidine (NTG) were determined for all genes of pathways from glucose to
      L-lysine in an industrial L-lysine producer of Corynebacterium glutamicum. A
      total of 50 mutations with a genome-wide distribution were identified and
      characterized for mutational types and mutagenic specificities. Those mutations
      were all point mutations with single-base substitutions and no deletions, frame
      shifts, and insertions were found. Among six possible types of base
      substitutions, the mutations consisted of only two types: 47 G.C-->A.T
      transitions and three A.T-->G.C transitions with no transversion. The findings
      indicate a limited repertoire of amino acid substitutions by classical NTG
      mutagenesis and thus raise a new possibility of further improving industrial
      strains by optimizing key mutations through PCR-mediated site-directed
      mutagenesis.

PMID- 18037339
TI  - Genetic polymorphisms and micronucleus formation: a review of the literature.
AB  - The formation of micronuclei (MN) is extensively used in molecular epidemiology
      as a biomarker of chromosomal damage, genome instability, and eventually of
      cancer risk. The occurrence of MN represents an integrated response to chromosome
      instability phenotypes and altered cellular viabilities caused by genetic defects
      and/or exogenous exposures to genotoxic agents. The present article reviews human
      population studies addressing the relationship between genetic polymorphisms and
      MN formation, and provides insight into how genetic variants could modulate the
      effect of environmental exposures to genotoxic agents, host factors (gender,
      age), lifestyle characteristics (smoking, alcohol, folate), and diseases
      (coronary artery disease, cancer). Seventy-two studies measuring MN frequency
      either in peripheral blood lymphocytes or exfoliated cells were retrieved after
      an extensive search of the MedLine/PubMed database. The effect of genetic
      polymorphisms on MN formation is complex, influenced to a different extent by
      several polymorphisms of proteins or enzymes involved in xenobiotic metabolism,
      DNA repair proteins, and folate-metabolism enzymes. This heterogeneity reflects
      the presence of multiple external and internal exposures, and the large number of
      chromosomal alterations eventually resulting in MN formation. Polymorphisms of
      EPHX, GSTT1, and GSTM1 are of special importance in modulating the frequency of
      chromosomal damage in individuals exposed to genotoxic agents and in unexposed
      populations. Variants of ALDH2 genes are consistently associated with MN
      formation induced by alcohol drinking. Carriers of BRCA1 and BRCA2 mutations
      (with or without breast cancer) show enhanced sensitivity to clastogens. Some
      evidence further suggests that DNA repair (XRCC1 and XRCC3) and folate-metabolism
      genes (MTHFR) also influence MN formation. As some of the findings are based on
      relatively small numbers of subjects, larger scale studies are required that
      include scoring of additional endpoints (e.g., MN in combination with fluorescent
      in situ hybridization, analysis of nucleoplasmic bridges and nuclear buds), and
      address gene-gene interactions.

PMID- 18037340
TI  - Real-time PCR for type-specific identification of herpes simplex in clinical
      samples: evaluation of type-specific results in the context of CNS diseases.
AB  - BACKGROUND: HSV-1 and HSV-2 cause CNS infections of dissimilar clinico
      pathological characteristics with prognostic and therapeutic implications.
      OBJECTIVES: To validate a type-specific real-time PCR that uses MGB/LNA Taqman
      probes and to review the virologico-clinical data of 25 eligible patients with
      non-neonatal CNS infections. RESULTS: This real-time PCR was evaluated against
      conventional PCR (26 CSF and 20 quality controls), and LightCycler assay (51
      mucocutaneous, 8 CSF and 32 quality controls) and culture/immunofluorescence (75
      mucocutaneous) to assess typing with independent methods. Taqman real-time PCR
      detected 240 HSV genomes per ml CSF, a level appropriate for the management of
      patients, and provided unambiguous typing for the 104 positive (62 HSV-1 and 42
      HSV-2) out the 160 independent clinical samples tested. HSV type diagnosed by
      Taqman real-time PCR predicted final diagnosis (meningitis versus
      encephalitis/meningoencephalitis, p<0.001) in 24/25 patients at time of
      presentation, in contrast to clinical evaluation. CONCLUSIONS: Our real-time PCR,
      as a sensitive and specific means for type-specific HSV diagnosis, provided rapid
      prognostic information for patient management.

PMID- 18037341
TI  - Application of a multivariate seizure detection and prediction method to non
      invasive and intracranial long-term EEG recordings.
AB  - OBJECTIVE: Retrospective evaluation and comparison of performances of a
      multivariate method for seizure detection and prediction on simultaneous long
      term EEG recordings from scalp and intracranial electrodes. METHODS: Two
      multivariate techniques based on simulated leaky integrate-and-fire neurons were
      investigated in order to detect and predict seizures. Both methods were applied
      and assessed on 423h of EEG and 26 seizures in total, recorded simultaneously
      from the scalp and intracranially continuously over several days from six
      patients with pharmacorefractory epilepsy. RESULTS: Features generated from
      simultaneous scalp and intracranial EEG data showed a similar dynamical behavior.
      Significant performances with sensitivities of up to 73%/62% for scalp/invasive
      EEG recordings given an upper limit of 0.15 false detections per hour were
      obtained. Up to 59%/50% of all seizures could be predicted from scalp/invasive
      EEG, given a maximum number of 0.15 false predictions per hour. A tendency to
      better performances for scalp EEG was obtained for the detection algorithm.
      CONCLUSIONS: The investigated methods originally developed for non-invasive EEG
      were successfully applied to intracranial EEG. Especially, concerning seizure
      detection the method shows a promising performance which is appropriate for
      practical applications in EEG monitoring. Concerning seizure prediction a
      significant prediction performance is indicated and a modification of the method
      is suggested. SIGNIFICANCE: This study evaluates simultaneously recorded non
      invasive and intracranial continuous long-term EEG data with respect to seizure
      detection and seizure prediction for the first time.

PMID- 18037342
TI  - Motor unit number estimation using high-density surface electromyography.
AB  - OBJECTIVE: To present a motor unit number estimation (MUNE) technique that
      resolves alternation by means of high-density surface EMG. METHODS: High-density
      surface EMG, using 120 EMG channels simultaneously, is combined with elements of
      the increment counting technique (ICT) and the multiple-point stimulation
      technique. Alternation is a major drawback in the ICT. The spatial and temporal
      information provided by high-density surface EMG support identification and
      elimination of the effects of alternation. We determined the MUNE and its
      reproducibility in 14 healthy subjects, using a grid of 8 x 15 small electrodes
      on the thenar muscles. RESULTS: Mean MUNE was 271+/-103 (retest: 290+/-109), with
      a coefficient of variation of 22% and an intra-class correlation of 0.88. On
      average, 22 motor unit potentials (MUPs) were collected per subject. The
      representativity of this MUP sample was quantitatively assessed using the
      spatiotemporal information provided by high-density recordings. CONCLUSIONS: MUNE
      values are relatively high, because we were able to detect many small MUPs.
      Reproducibility was similar to that of other MUNE techniques. SIGNIFICANCE: Our
      technique allows collection of a large MUP sample non-invasively by resolving
      alternation to a large extent and provides insight into the representativity of
      this sample. The large sample size is expected to increase MUNE accuracy.

PMID- 18037343
TI  - High-frequency gamma activity (80-150Hz) is increased in human cortex during
      selective attention.
AB  - OBJECTIVE: To study the role of gamma oscillations (>30Hz) in selective attention
      using subdural electrocorticography (ECoG) in humans. METHODS: We recorded ECoG
      in human subjects implanted with subdural electrodes for epilepsy surgery.
      Sequences of auditory tones and tactile vibrations of 800 ms duration were
      presented asynchronously, and subjects were asked to selectively attend to one of
      the two stimulus modalities in order to detect an amplitude increase at 400 ms in
      some of the stimuli. RESULTS: Event-related ECoG gamma activity was greater over
      auditory cortex when subjects attended auditory stimuli and was greater over
      somatosensory cortex when subjects attended vibrotactile stimuli. Furthermore,
      gamma activity was also observed over prefrontal cortex when stimuli appeared in
      either modality, but only when they were attended. Attentional modulation of
      gamma power began approximately 400 ms after stimulus onset, consistent with the
      temporal demands on attention. The increase in gamma activity was greatest at
      frequencies between 80 and 150 Hz, in the so-called high-gamma frequency range.
      CONCLUSIONS: There appears to be a strong link between activity in the high-gamma
      range (80-150 Hz) and selective attention. SIGNIFICANCE: Selective attention is
      correlated with increased activity in a frequency range that is significantly
      higher than what has been reported previously using EEG recordings.

PMID- 18037345
TI  - Phage display: a useful tool for malaria research?
AB  - Defining the molecular intricacies of malaria pathogenesis is a vital area of
      medical and scientific research. Sophisticated methods have been developed to
      identify and characterise host-parasite interactions that are important in
      infection. Phage display involves the combinatorial display of proteins or
      peptides on the surface of bacteriophage. The technology provides an invaluable
      tool for screening diverse libraries for polypeptides that have a high affinity
      for a given target. Phage display in malaria research has proven successful, not
      only in mapping the protein-protein interactions that are important in Plasmodium
      biology, but also in the identification of molecules that might be exploited in
      the design of therapeutic agents or vaccines.

PMID- 18037346
TI  - Spuriously high phosphate level which is promptly resolved after plasmapheresis
      in a patient with multiple myeloma.
AB  - We present a 57 year old female patient with IgG multiple myeloma and marked
      hyperphosphatemia. The patient had no clinical symptoms related to
      hyperphosphatemia. Serum inorganic phosphate measurements were repeated on
      sulfosalicylic acid deproteinized serum samples, yielding normal phosphate
      levels. We realized that this hyperphosphatemia was spurious because of high
      paraprotein levels. Afterwards, therapeutic plasma exchange (TPE) was
      administered due to hyperviscosity and bleeding tendency. After the
      administration of TPE, serum phosphate was reduced to normal level. Therapeutic
      plasma exchange resulted in steady-state serum phosphate levels during the three
      months follow up period. We concluded that high phosphate levels must be
      confirmed by measuring in deproteinized serum samples in multiple myeloma
      patients in order to distinguish pseudohyperphosphatemia from the true ones. In
      addition, TPE effectively reduces the spuriously elevated phosphate levels
      possibly by removing paraproteins.

PMID- 18037344
TI  - Eating for pleasure or calories.
AB  - A changing environment and lifestyle on the background of evolutionary engraved
      or perinatally imprinted physiological response patterns is the foremost
      explanation for the current obesity epidemic. However, it is not clear what the
      mechanisms are by which the modern environment overrides the physiological
      controls of appetite and homeostatic body weight regulation. Major advances have
      been made regarding crosstalk between metabolic signals and the
      cognitive/emotional brain that primarily deals with the environment. On one hand,
      metabolic signals such as leptin and ghrelin have previously unexpected direct
      effects on learning and memory, as well as liking and wanting. On the other hand,
      brain areas involved in reward, cognition, and executive control can override
      metabolic regulation by talking to the hypothalamus.

PMID- 18037347
TI  - Clinical features, long-term follow-up and outcome of a large cohort of patients
      with Chronic Granulomatous Disease: an Italian multicenter study.
AB  - A retrospective clinical and immunological survey was conducted in 60 patients
      with Chronic Granulomatous Disease. A prospective controlled non-randomized study
      of the efficacy of long-term IFNgamma treatment was carried out. The mean age at
      the time of diagnosis was 4.4 years; mean duration of follow-up was 10.4 years.
      Lung and skin infections were the most frequent manifestations both prior to
      diagnosis and during follow-up. Aspergillus species was the first cause of
      infection and of death in our cohort. The mortality rate was 13%. Long term
      prophylaxis with IFNgamma did not significantly change the rate of total
      infection per patient-year compared to controls (p=0.07). Our data provide clear
      evidence that protocols of continuing intensive surveillance and monitoring of
      compliance with anti-infective regimens may significantly improve the quality of
      life and long-term survival in patients with CGD. No evidence justifying long
      term prophylaxis with IFNgamma was obtained.

PMID- 18037348
TI  - Catastrophic intramedullary hematoma following Kummell's disease with large
      intravertebral cleft.
AB  - BACKGROUND CONTEXT: Kummell's disease is defined as avascular osteonecrosis and
      occurs after delayed posttraumatic vertebral collapse. Devastating cord injury
      with Kummell's disease is rare except in advanced cases with kyphosis and
      posterior cortex breakage. PURPOSE: The authors report unique experience with
      patients who presented with a catastrophic intramedullary hematoma after early
      stage Kummell's disease without kyphosis. STUDY DESIGN: Case report with analysis
      of the literature. METHODS: A 72-year-old woman with osteoporotic vertebral
      fractures of T12 visited the emergency room complaining of persistent back pain
      and paraparesis. The plain radiographic examination revealed mild osteoporotic
      wedge compression fractures. The magnetic resonance images revealed the fracture
      cavity as a discrete area of abnormal low and high signal, which is consistent
      with vertebral osteonecrosis with evidence of Kummell's disease on T12, and conus
      showing an extensive hematoma with mixed signal changes. RESULTS: The authors
      performed laminectomy and the removal of the intramedullary hematoma, followed by
      vertebroplasty on T12. The spinal column was reduced and fixed posteriorly with a
      pedicle screw system using a one-stage procedure. CONCLUSIONS: An increasing
      awareness of the delayed vertebral collapse with cord injury attached to an
      osteoporotic spine fracture, as well as a periodic follow-up and treatment are
      essential for preventing catastrophic neurological impairment.

PMID- 18037349
TI  - Metastasis of carcinoid to the arch of the axis in a multiple endocrine neoplasia
      patient: a case report.
AB  - BACKGROUND CONTEXT: Carcinoid tumors eventually metastasize to the spine, and
      epidural spinal cord compression is a relatively frequent neurologic complication
      of carcinoid. However, a case of multiple endocrine neoplasia type 1 (MEN1)
      presenting with spinal cord compression as a result of a metastatic carcinoid
      tumor has not been reported previously. PURPOSE: To report an extremely rare case
      of MEN1 presenting with spinal cord compression by metastatic carcinoid tumor.
      STUDY DESIGN: Case report. METHODS: A 51-year-old man, with a past history of
      thymoma, insulinoma, and gastric carcinoid presented with neck pain.
      Neuroradiological examination revealed that a tumor around the arch of the axis
      compressed the spinal cord with osteoblastic changes. RESULTS: After
      hemilaminectomy of the axis and removal of the tumor followed by irradiation, the
      patient returned to his previous job. Histological examination confirmed
      metastatic carcinoid tumor. CONCLUSIONS: Spinal metastasis of carcinoid tumor
      occurred in a multiple endocrine neoplasia patient, and it is significant to note
      that carcinoid metastasis is one of differential diagnoses for osteoblastic
      lesions.

PMID- 18037350
TI  - Use of instrumented pedicle screws to evaluate load sharing in posterior dynamic
      stabilization systems.
AB  - BACKGROUND CONTEXT: Dynamic stabilization is an alternative to fusion intended to
      eliminate or at least minimize the potential for adjacent level degeneration.
      Different design approaches are used in pedicle screw-based systems that should
      have very different effects on the loading of the posterior column and
      intervertebral disc. If the implant system distributes these loads more evenly,
      loads in the pedicle screws will be reduced, and screw loosening will be
      prevented. PURPOSE: The purpose of this study was to determine how two different
      design approaches to dynamic stabilization systems, Dynesys System and the Total
      Posterior Spine (TOPS) System, affect the load carried by the pedicle screws.
      STUDY DESIGN/SETTING: A controlled laboratory study in which the magnitude of the
      moments on pedicle screws during flexion-extension and lateral bending were
      measured after implantation of two posterior dynamic stabilization devices into
      cadaveric spines. METHODS: Five lumbar spines were tested in flexion-extension
      and lateral bending. Specimens were tested sequentially: first intact, then with
      the Dynesys system implanted, and finally with the TOPS system implanted. Range
      of motion (ROM) for each construct was measured with a 210N and 630N compressive
      load. The pedicle screws were instrumented with strain gages, which were
      calibrated so that the moments on the screws could be determined from the strain
      measurements. RESULTS: Compared with intact values, ROM decreased in flexion
      extension and lateral bending when the Dynesys System was implanted. With
      implantation of the TOPS System, ROM returned to values that were not
      significantly different from the intact values. The moments in the screws with
      the Dynesys System were significantly higher than with the TOPS System with
      increases of as much as 56% in flexion-extension and 86% in lateral bending.
      CONCLUSIONS: The design of the posterior stabilization device influences the
      amount of load seen by the pedicle screws and therefore the load sharing between
      spinal implant and bone.

PMID- 18037352
TI  - Neurologic impairment from ectopic bone in the lumbar canal: a potential
      complication of off-label PLIF/TLIF use of bone morphogenetic protein-2 (BMP-2).
AB  - BACKGROUND CONTEXT: Bone morphogenetic protein-2 (BMP-2) (Infuse) has been
      approved for use in anterior lumbar fusion in conjunction with an LT cage.
      However, off-label use is seen with anterior cervical fusion, posterior lumbar
      interbody fusion (PLIF), and transforaminal lumbar interbody fusion (TLIF). The
      Federal Food and Drug Administration trial of BMP-2 in a PLIF application was
      halted because of a high incidence of ectopic bone forming in the neural canal
      (75%). The authors did not find a correlation between ectopic bone and increased
      leg pain. They concluded that the ectopic bone was a radiographic phenomenon and
      not associated with clinical findings. Complications using BMP in the cervical
      spine have been reported. Heretofore, there has not been a similar warning voiced
      for use of BMP in a lumbar PLIF or TLIF. PURPOSE: The purpose was to report five
      cases of ectopic bone in the canal associated with PLIF/TLIF off-label use of BMP
      2 potentially contributing to abnormal neurologic findings. STUDY DESIGN/SETTING:
      This is an observational cohort study of patients referred to a tertiary care
      private medical center. METHODS: This was a retrospective chart review of
      patients referred to a tertiary spine institute with complications after surgery
      where BMP-2 had been used in an off-label PLIF or TLIF application. Patient
      demographics, operating room (OR) notes from the index BMP surgery, imaging
      studies, and current clinical status were reviewed. RESULTS: Five cases of
      ectopic bone in the spinal canal with potential neurologic compromise were
      identified. CONCLUSIONS: It does appear that ectopic bone in the spinal canal
      associated with BMP-2 use in PLIF or TLIF may contribute to symptomatic
      neurologic findings in rare cases. Revision surgeries are difficult. This article
      challenges a previous publication, which concluded that the high incidence of
      ectopic bone was of no clinical significance. Isolating BMP anteriorly in the
      disc space using layered barriers of bone graft between the BMP and the annular
      defect may reduce the incidence of ectopic bone in the spinal canal. Surgeons
      need to weigh the benefits versus risks of any technology used off label when
      making treatment decisions with their patients.

PMID- 18037351
TI  - Mature runt cow lumbar intradiscal pressures and motion segment biomechanics.
AB  - BACKGROUND CONTEXT: The optimal animal model for in vivo testing of spinal
      implants, particularly total or partial disc replacement devices, has not yet
      been determined. Mechanical and morphological similarities of calf and human
      spines have been reported; however, limitations of the calf model include open
      growth plates and oversized vertebrae with growth. Mature runt cows (Corrientes
      breed) may avoid these limitations. PURPOSE: This study compared vertebral
      morphology and biomechanical properties of human and runt cow lumbar motion
      segments. STUDY DESIGN: In vivo disc pressure measurements were obtained in six
      mature runt cows at L4-L5. In vitro evaluation was performed on these same
      segments and repeated on 12 human motion segments. METHODS: Disc pressures were
      measured in vivo in runt cow (Corrientes breed) L45 discs using a percutaneous
      transducer with the animal performing various activities. These motion segments
      were then harvested and morphologic and biomechanical evaluations (disc pressure
      in compression, flexibility tests to 7.5Nm) were performed on both cow and male
      human L23 and L45 segments. RESULTS: The transverse lumbar disc dimensions were
      slightly smaller for (mixed gender) cow versus (male) humans, but were within the
      range of reported (mixed gender) human values. The mean+/-SD disc height was
      smaller for runt cow (7+/-1mm) versus human discs (13+/-2mm, p<.001). The
      vertebral bodies of the cow were approximately twice as tall as the human. In
      vitro testing revealed significantly greater disc pressure response to applied
      axial loading in the runt cow versus humans (1.27+/-0.18 vs. 0.84+/-0.15kPa/N,
      respectively) but similar overall stiffness (2.15+/-0.71 vs. 1.91+/-0.94kN/mm,
      respectively). Runt cow and human segment flexibility curves were similar with
      the following exceptions: runt cow stiffness was approximately 40% greater in
      torsion (p<.05), runt cow segment lateral bending motion was greater versus
      humans (range of motion by 30%, neutral zone by 100%; both p<.05), and flexion
      range of motion tended to be smaller in runt cow versus human specimens (by
      approximately 40%, p=NS). In vivo, the standing disc pressure in the runt cow was
      0.80+/-0.24MPa. CONCLUSIONS: Although no animal replicates the human motion
      segment, the runt cow lumbar spine had a number of biomechanical and
      morphological measurements within the range of human values. The closed physes
      and temporally stable morphology of the mature runt cow may make this model more
      suitable versus standard calf models for human intradiscal implant studies.

PMID- 18037353
TI  - Factors associated with lumbar intervertebral disc degeneration in the elderly.
AB  - BACKGROUND CONTEXT: Lumbar intervertebral disc degeneration (DD) precedes
      degenerative diseases of the lumbar spine. Various factors in addition to normal
      aging are reported to be associated with DD, and recently atherosclerosis and
      risk factors for cardiovascular diseases (cardiovascular risk factors) have
      received much attention; however, the links between these risk factors and DD are
      unclear. PURPOSE: By correlating magnetic resonance images (MRI) with suspected
      degenerative disc risk factors such as obesity, cardiovascular risk factors, and
      atherosclerosis, we hope to clarify the factors associated with DD. STUDY
      DESIGN/SETTING: An observational study. PATIENT SAMPLE: Two hundred seventy
      adults (51-86 years old) who participated in a health promotion program. OUTCOME
      MEASURES: DD evaluated based on the signal intensity of MR T2-weighted mid
      sagittal images of the lumbar spine. METHODS: Age, gender, body mass index (BMI),
      low-density lipoprotein cholesterol (LDLc), triglyceride (TG), glycosylated
      hemoglobin (HbA(1c)), brachial-ankle pulse wave velocity (baPWV) as an index of
      atherosclerosis, osteo-sono-assessment index (OSI) calculated from quantitative
      ultrasound assessment of the calcaneus as an index of bone mineral density (BMD),
      history of low back pain (LBP), smoking and drinking habits, and physical loading
      related to occupations and sports were assessed. The univariate relationships
      between DD and the variables were evaluated, and finally, odds ratios (OR) and
      95% confidence intervals (CI) for the associations of each factor with DD were
      calculated using logistic regression at each disc level. RESULTS: Aging
      correlated significantly with DD of L1/2 (OR, 2.14), L2/3 (OR, 3.56), L3/4 (OR,
      2.84), and L4/5 (OR, 3.05); high BMI, with L2/3 (OR, 2.98), L3/4 (OR, 3.58), L4/5
      (OR, 2.32), and L5/S1 (OR, 3.34); high LDLc, with L4/5 (OR, 2.65); occupational
      lifting, with L1/2 (OR, 4.25); and sports activities, with L5/S1 (OR, 3.36).
      CONCLUSIONS: Aging, high BMI, high LDLc, occupational lifting, and sports
      activities are associated with DD. The results of this study raise our index of
      suspicion that cardiovascular risk factors and particular physical loading may
      contribute to DD; however additional studies are required to further investigate
      associations between DD and these factors.

PMID- 18037354
TI  - Fusion and nonsurgical treatment for symptomatic lumbar degenerative disease: a
      systematic review of Oswestry Disability Index and MOS Short Form-36 outcomes.
AB  - BACKGROUND CONTEXT: Although numerous studies have been published, controversy
      still exists regarding fusion and nonsurgical treatment for symptomatic
      degenerative lumbar spine conditions. Definite conclusions are difficult to draw
      because of differences in patient inclusion criteria, fusion technique,
      nonoperative treatment regimen, and clinical outcome measures used to determine
      success. PURPOSE: The objective of this study was to evaluate lumbar fusion and
      nonsurgical interventions for various degenerative spine disorders using the
      Oswestry Disability Index (ODI) as a primary outcome measure in a systematic
      review. A secondary objective was to determine whether there is a difference in
      clinical outcomes based on the specific diagnosis. STUDY DESIGN/SETTING:
      Systematic review. PATIENT SAMPLE: Patients with low back pain of at least 12
      weeks duration and older than 18 years, with prospectively collected ODI scores
      and at least a 12-month follow-up. OUTCOME MEASURES: ODI and Short Form-36 (SF
      36). METHODS: A MEDLINE, HealthSTAR, CINAHL, and Cochrane database search was
      done using the search strategy recommended by the Cochrane Back Review Group.
      Proceedings from annual meetings of various spine societies and reference lists
      from review articles and retrieved articles were evaluated for possible
      inclusion. Criteria for inclusion were prospective randomized clinical trials in
      patients with low back pain of at least 12 weeks duration and older than 18
      years; with prospectively collected ODI scores and at least a 12-month follow-up.
      The methodological quality of the studies was assessed using the van Tulder
      criteria. Data extracted from each study included demographics, study design,
      diagnosis, baseline and change in ODI, and baseline and change in SF-36 Physical
      Composite Score (PCS). The data were pooled and analyzed based on the primary
      reported inclusion diagnosis: degenerative disc disease (DDD), chronic low back
      pain (CLBP), and spondylolisthesis; and treatment: fusion (unspecified,
      posterior, anterior, combined) and nonsurgical. RESULTS: Twenty-five studies met
      the inclusion criteria. The distribution of sex and smokers was similar across
      diagnoses and treatments. Patients with spondylolisthesis were older than
      patients with DDD and CLBP. Patients with spondylolisthesis had the greatest ODI
      improvement followed by patients with DDD and CLBP. The three fusion types
      produced similar amounts of improvement in ODI. Nonsurgical patients did not
      improve as much but had a lower baseline ODI. Improvements in the SF-36 PCS were
      fairly consistent across diagnostic groups and treatment types. CONCLUSIONS:
      Substantial improvement can be expected in patients treated with fusion,
      regardless of technique, when an established indication such as spondylolisthesis
      or DDD exists. CLBP patients are less disabled and experience less improvement.

PMID- 18037355
TI  - Is a videotape to change beliefs and behaviors superior to a standard videotape
      in acute low back pain? A randomized controlled trial.
AB  - BACKGROUND CONTEXT: Cognitive behavioral therapy has been used successfully in
      acute low back pain (LBP) treatment, but the use of a cognitive behavioral
      videotape as an adjunct to treatment has not been studied. PURPOSE: To determine
      outcomes for patients with acute LBP receiving a videotape designed to change
      beliefs and behaviors compared with a standard instructional videotape. STUDY
      DESIGN/SETTING: Randomized controlled trial; multidisciplinary clinic in an
      academic setting. PATIENT SAMPLE: Consecutive subjects with less than 3 months of
      LBP. Of 224 eligible subjects, 138 participated and completed the initial
      questionnaires. OUTCOME MEASURES: Oswestry Disability Index, Pain and Impairment
      Relationship Scale, Fear-Avoidance Beliefs Questionnaire; medical costs related
      to LBP and total medical costs incurred by participants during 1 year of follow
      up. METHODS: Subjects were randomly assigned to receive a behavioral videotape or
      a control videotape. Other than the videotape, usual care was provided to each
      patient. RESULTS: No significant differences in any outcome measures or medical
      costs between the two groups at 12 months. However, baseline Vermont Disability
      Prediction Questionnaire was significantly lower in those who completed the
      entire study compared with those who did not complete the study. CONCLUSIONS:
      Compared with a standard instructional videotape, a behavioral videotape did not
      change beliefs, outcomes, or costs over 1 year. Cost-effective behavioral
      interventions with high patient retention rates are needed, especially for those
      at greatest risk of high utilization of resources.

PMID- 18037356
TI  - A comparison of anatomy-based inverse planning with simulated annealing and
      graphical optimization for high-dose-rate prostate brachytherapy.
AB  - BACKGROUND AND PURPOSE: Dose distribution in a high-dose-rate (HDR) brachytherapy
      implant is optimized by adjusting source dwell positions and dwell times along
      the implanted catheters. Inverse planning with fast simulated annealing (IPSA) is
      a recently developed algorithm for anatomy-based inverse planning, capable of
      generating an optimized plan in less than 1min. The purpose of this study is to
      compare dose distributions achieved using IPSA to those obtained with a graphical
      optimization (GrO) algorithm for prostate HDR brachytherapy. METHODS AND
      MATERIALS: This is a retrospective study of 63 consecutive prostate HDR
      brachytherapy implants planned and treated using on-screen GrO to a dose of 10Gy
      per implant. All plans were then recalculated using IPSA, without changing any
      parameters (contours, catheters, number, or location of dwell positions). The
      IPSA and GrO plans were compared with respect to target coverage, conformality,
      dose homogeneity, and normal tissue dose. RESULTS: The mean volume of target
      treated to 100% of prescription dose (V(100)) was 97.1% and 96.7%, and mean
      Conformal Index 0.71 and 0.68 with GrO and IPSA, respectively. IPSA plans had a
      higher mean homogeneity index (0.69 vs. 0.63, p<0.001) and lower volume of target
      receiving 150% (30.2% vs. 35.6%, p<0.001) and 200% (10.7% vs. 12.7%, p<0.001) of
      the prescription dose. Mean dose to urethra, rectum, and bladder were all
      significantly lower with IPSA (p<0.001). IPSA plans tended to be more
      reproducible, with smaller standard deviations for all measured parameters.
      CONCLUSIONS: Plans generated using IPSA provide similar target coverage to those
      obtained using GrO but with lower dose to normal structures and greater dose
      homogeneity.

PMID- 18037357
TI  - Endogenous urea as an autacoid: extrarenal and renal focuses.
AB  - The present position article complies with selected own and literature data
      concerning the characterization of endogenous urea at extrarenal level in animal
      and human organism in functional aspect. With key pharmacological experiments,
      both under in vivo and in vitro conditions, we apply urea in concentrations
      corresponding to physiological and pathological ones. We established that
      endogenous urea (without use as an exogenous applied drug) possesses important
      properties. It is assumed that urea is an endogenous non-specific beta-adrenergic
      receptor antagonist (ENBARA), non-selective, non-competitive, reversible and non
      toxic. Based on these data we develop a concept for endogenous beta-adrenergic
      receptor antagonists (EBARA). In agreement with proofs of RJ Lefkowitz' group in
      the 90-ies that "beta arrestines 1 and 2 antagonize three of four agonist
      activated beta-adrenergic receptors" we accept that they act as relatively
      endogenous specific beta-adrenergic receptor antagonists (RESBARA). As regards
      for the last four beta-agonist-activated adrenergic receptor we propose that is
      controlled via ENBARA. That is why a new role of urea is to be in the list of
      endocoids (autacoids).

PMID- 18037358
TI  - Experience of plastic surgery as an undergraduate--vital for the future of the
      specialty!

PMID- 18037359
TI  - Periareolar reduction mammoplasty using an inferior dermal pedicle or a central
      pedicle.
AB  - The goals of reduction mammoplasty are to reduce the volume of a breast, to
      create an aesthetic shape that is stable over time, to maintain blood supply and
      innervation to the areolar complex, and to make fine limited scars. The present
      authors used periareolar reduction mammoplasty using an inferior dermal pedicle
      or a central pedicle. To minimise the scar, periareolar incision was performed.
      To reduce the volume of breast and to preserve blood supply and innervation to
      the nipple-areolar complex, a central or an inferior pedicle technique was used.
      To prevent areolar widening, a purse-string suture was used. A total of 82
      breasts in 41 patients with very large breasts were operated on between July 1998
      and June 2004. The mean age was 39, and the mean resection amount was 389 g per
      breast (right 413 g, left 364 g) with an average follow up of 28 months. Most of
      the patients were satisfied with the fine periareolar scar, the size of the
      breasts and the sensation of the nipple-areolar complex. The present authors have
      applied this procedure to all kinds of macromastia. Although the advantages of
      the periareolar reduction mammoplasty are an inconspicuous limited scar, a
      preservation of sensation to the nipple-areolar complex and a short operation
      time, 24 breasts (29%) showed areolar widening. There were persistent periareolar
      wrinkles in eight breasts (10%) and poor sensation to the nipple-areolar complex
      in 12 breasts (15%), in which more than 500 g of breast tissue was removed per
      breast. In conclusion, the periareolar reduction mammoplasty is optimal for
      patients who require a reduction of less than 500 g per breast. In severe
      macromastia with or without ptosis, the inverted T-incision is more preferable to
      periareolar incision, and periareolar incision can be modified by adding a wedge
      resection of the outer excess in skin flap inferiorly, which results in
      periareolar and vertical scars below the nipple-areolar complex.

PMID- 18037360
TI  - A study of perfusion of the distal free-TRAM flap using laser Doppler flowmetry.
AB  - The aim of this study was to characterise microcirculatory changes in the distal
      part of a flap and to evaluate whether measurement of the microcirculation may
      predict flap complications (FC). In this prospective study, 30 patients
      undergoing a delayed breast reconstruction were included. Perioperative data were
      recorded and with the laser Doppler flowmetry (LDF; Perimed) blood flow was
      recorded in the central part (zone I) and the distal part (zone IV) of the flap.
      A lower blood flow was observed in zone IV of patients with flap complications
      compared to patients without flap complications (P=0.013). In addition, LDF
      demonstrated different flow trends in zone I compared to zone IV indicating a
      delayed opening of the choke vessels connecting the angiosomes in the distal part
      of the flap. The LDF has proven to be a useful investigative tool to monitor
      microcirculatory changes. In future studies it will be used to evaluate
      interventions aimed at decreasing distal ischaemia and reducing flap
      complications.

PMID- 18037361
TI  - Aesthetic outcome after nasal reconstruction: patient versus panel perception.
AB  - SUMMARY BACKGROUND: Nasal reconstruction after extensive ablative therapy poses a
      reconstructive challenge. The aim of this study was to assess subjective
      aesthetic outcome after nasal reconstruction scored by patients and a panel. In
      addition, inter-rater variability as well as important parameters of good
      aesthetic outcome were analysed. METHODS: A total of 39 consecutive patients
      treated between November 2001 and May 2005 for (sub) total nasal defects were
      included. All patients were photographed in a standardised setting. Subjective
      aesthetic outcome (eight different nasal characteristics on a five-point Likert
      scale) was assessed by reconstructed patients individually as well as an
      independent professional panel consisting of five plastic surgeons. RESULTS:
      Thirty-three patients (87%) participated in the follow-up study. Questionnaire
      results demonstrated statistically significant lower panel satisfaction scores
      (3.5+/-0.9) with total nasal appearance than patients (4.2+/-1.3; P=0.03). There
      was a high agreement among panel members as judged by a low inter-rater
      variability. No relationship between severity of nasal defects and aesthetic
      outcome was found by patients or professionals. CONCLUSION: Patient subjective
      aesthetic outcome was significantly higher than that of a professional panel.
      Severity of nasal deformity was not an indicator for patient satisfaction.

PMID- 18037362
TI  - Methods and normal values for echocardiography in adult dairy cattle.
AB  - OBJECTIVE: The objective of the study was to report normal ultrasonographic
      appearance and intra-cardiac dimensions in two dairy breeds and to calculate
      cardiac output (CO) using echocardiography. BACKGROUND: Intra-cardiac dimensions,
      time indices and CO estimation have not previously been reported in adult cattle.
      ANIMALS, MATERIALS AND METHODS: Echocardiograms were obtained from healthy adult
      dairy cows (10 Jersey (J) and 12 Holstein Friesians (HF)) in the body weight
      range of 400 to 700 kg. Standard echocardiographic images were obtained from the
      left and right hemithoraces. Velocity time integrals were obtained in order to
      calculate CO using pulsed wave Doppler of aortic flow in the J cows. Measurements
      obtained included pulmonary artery and aortic diameters, left and right
      ventricular diameters (and calculated fractional shortening and left ventricular
      ejection fraction), left atrial size and time indices assessing valve function.
      RESULTS: HF cows had significantly (p<0.05) larger pulmonary artery and aortic
      diameters, larger left atrial diameters and left ventricular internal diameters
      during diastole, but these were not different when corrected for body weight.
      Left and right ventricular dimensions, adjusted for body weight, were
      significantly larger (p=0.02 and p=0.035 respectively) in J cows when compared to
      HF cows. No differences were noted in the time indices between the two groups. No
      significant differences were noted in intra-operator variability and the only
      significant difference in inter-operator variability was in measurement of the
      pulmonary artery (p=0.03; ICC=0.63). CONCLUSIONS: It is possible to obtain
      repeatable, reliable echocardiograms in order that meaningful intra-cardiac
      dimensions can be obtained in adult dairy cattle.

PMID- 18037363
TI  - Radial strain and strain rate by two-dimensional speckle tracking
      echocardiography and the tissue velocity based technique in the dog.
AB  - OBJECTIVES: Two-dimensional (2D) speckle tracking echocardiography (STE) is a new
      angle-independent ultrasound technique based on tracking of speckles within the
      myocardium on 2D grayscale images. The aims of this prospective study were as
      follows: (1) to assess the variability of left ventricular peak systolic radial
      strain (St) and strain rate (SR) in awake dogs using STE (Protocol 1); and (2) to
      quantify these variables in a healthy canine population and compare them with
      tissue Doppler imaging (TDI)-based St and SR values (Protocol 2). BACKGROUND: St
      and SR may be assessed using TDI, which is limited by angle dependency. ANIMALS,
      MATERIALS AND METHODS: Thirty-six STE examinations were performed on 6 healthy
      dogs for Protocol 1 and 37 healthy dogs were recruited for Protocol 2. In both
      studies, STE measurements were obtained offline from the right parasternal short
      axis view by the same trained observer using automatic frame-to-frame tracking of
      grayscale speckle patterns. RESULTS: All within- and between-day coefficients of
      variation were <10% (Protocol 1). In Protocol 2, St (46.7+/-12.2%) and SR (2.7+/
      0.6s(-1)) measured by STE were correlated with heart rate (p<0.01), but not with
      the ratio of early mitral inflow velocity to early mitral annular velocity. There
      was a good correlation between STE and TDI for both St and SR values (p<0.001).
      CONCLUSIONS: STE is a repeatable and reproducible non-Doppler method for
      assessing radial St and SR. The combination of these indices with conventional
      echo-Doppler variables could provide a new approach for accurately quantifying
      canine systolic function.

PMID- 18037364
TI  - Bone formation in spontaneously diabetic Torii-newly established model of non
      obese type 2 diabetes rats.
AB  - It is well known that patients with type 1 diabetes mellitus exhibit bone
      abnormalities as one of the complications of the disease. Whether this occurs in
      type 2 diabetes is controversial. This uncertainty could be because type 2
      diabetes includes several pathological types such as obese and non-obese. To
      examine the bone abnormalities in non-obese type 2 diabetes, we used
      Spontaneously Diabetic Torii (SDT) rats, which is a newly established model of
      non-obese type 2 diabetes. Sprague-Dawley (SD) rats were used as a control group
      (n=17). SDT rats were divided into two groups: the diabetic (DM) group (n=18) and
      the DM+insulin (INS) group (n=18) at 20 weeks of age. The DM+INS group received
      subcutaneously implanted insulin pellets every 2 weeks. At 36 weeks of age, the
      rats were killed, and we evaluated bone formation and the effect of insulin on
      bone formation, blood and urine analyses, bone mineral density (BMD),
      histomorphometry, and mRNA expression of alkaline phosphatase (ALP) and
      osteocalcin (OCN). Despite renal function not being impaired, BMD and bone
      strength were significantly lower in the DM group than in the control group.
      Osteoid volume per bone volume, osteoblast surface per bone surface, eroded
      surface per bone surface, osteoclast surface per bone surface, the mineral
      apposition rate, and the bone formation rate per bone surface were significantly
      lower in the DM group than in the control and DM+INS groups. The mRNA expression
      of ALP and OCN was significantly lower in the DM group than in the control group.
      Furthermore, 8-hydroxydeoxyguanosine, which is an oxidative stress marker, was
      remarkably elevated in the DM group. These abnormalities were recovered by
      insulin therapy. Our data support the notion that non-obese type 2 diabetes is
      associated with a low turnover of bone and that the abnormalities are ameliorated
      by insulin. The SDT rat may be a useful animal model for examining the mechanisms
      of bone abnormalities in non-obese type 2 diabetes.

PMID- 18037365
TI  - The RIZ Pro704 insertion-deletion polymorphism, bone mineral density and fracture
      risk: the Rotterdam study.
AB  - Estrogens play a major role in the maintenance of bone and bone strength, and
      they exert their effects via estrogen receptors. Recently, an estrogen receptor
      alpha (ESR1) specific co-activator, retinoblastoma-interacting zinc-finger
      protein (RIZ1, 1p36), was shown to strongly enhance ESR1 function in vitro. The
      same study showed that a Proline insertion-deletion polymorphism at amino acid
      position 704 (Pro704 ins/del) in the RIZ1 gene was associated with heel BMD in
      young Swedish women. We tested the relation between the RIZ1 Pro704 ins/del
      polymorphism and BMD and fracture risk in Caucasian elderly men and women of the
      Rotterdam study. We also examined whether estradiol levels (measured in a subset)
      or genetic variation in ESR1 influenced this relation. In 2424 men and 3517 women
      from the Rotterdam study, RIZ1 genotypes were determined and associations with
      BMD (lumbar spine and femoral neck) and fracture risk were analysed. We recorded
      374 vertebral fractures at baseline and during 6.4+/-0.4 (SD) years of follow-up,
      and 1219 incident non-vertebral fractures during 7.4+/-3.3 (SD) years of follow
      up. The allele frequency of the Pro704 insertion was 41%, the genotype
      distribution was in Hardy-Weinberg Equilibrium (P=0.94). We found no association
      of this polymorphism with BMD or fracture risk. Stratification for gender,
      estradiol levels or interaction with ESR1 risk haplotype did not change these
      results. In conclusion, in this large study we observed no association of the
      RIZ1 Pro704 insertion-deletion polymorphism with BMD or fracture risk. This
      suggests this polymorphism to play a minor role, if any, as a genetic determinant
      of osteoporosis in elderly subjects.

PMID- 18037366
TI  - Epidemiology of hip fracture in the elderly in Spain.
AB  - OBJECTIVE: To describe the incidence and epidemiological characteristics of hip
      fracture (HF) in patients aged 65 years or over in the various autonomous regions
      (AR) of Spain from the year 2000 to 2002 and to determine which factors affect in
      hospital mortality. METHODS: Retrospective, observational study including all
      patients aged >65 years with acute hip fracture in the 19 AR of Spain from 2000
      to 2002. Data were obtained from the National Record of the Minimum Basic Data
      Set of the Ministry of Health. We analyzed the following: incidence rates (crude
      and age- and gender-adjusted rates) and incidence of hospital admission by
      season, length of hospital stay and in-hospital mortality. We used regression
      analysis to identify the factors that influenced in-hospital mortality. RESULTS:
      There were 107,718 cases of HF in patients aged >65 years; of these, 74% were
      women, with a mean age of 79 years (SD 14). The crude incidence rate for HF was
      511 cases per 100,000 >65-year-old patients per year (265 cases per 100,000 men
      and 688 per 100,000 women and year). Incidence adjusted for age and gender was
      503 cases per 100,000 inhabitants per year. Catalonia had the highest age
      adjusted incidence and Galicia the lowest (623 and 317 cases per 100,000
      inhabitants per year, respectively). Incidence rates increased from spring
      (24.1%) to winter (25.8%). The mean length of hospital stay was 15 days (SD 13).
      Seasonal influence and length of stay varied greatly between autonomous regions.
      While the overall in-hospital mortality rate was 5.3%, the rate for males was
      double that of females (8.9% and 4.8%, respectively), and in-hospital mortality
      increased with comorbidity (each point on the Charlson index increased mortality
      by 34.5%) was higher in winter (11% more risk compared to warmer seasons) and in
      cold climate regions (15% more risk compared to regions with a warm climate,
      i.e.: Catalonia, Valencia, Murcia, Andalusia, Balearic Islands and Canary
      Islands). CONCLUSIONS: Hip fracture mainly affects elderly women and presents
      great variability in incidence, seasonality, length of hospital stay and
      mortality between the different autonomous regions in Spain. Elderly male
      patients with severe comorbid conditions, who are admitted in winter and in cold
      climate regions are more at risk of in-hospital mortality.

PMID- 18037367
TI  - Decreased bone turnover with balanced resorption and formation prevent cortical
      bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).
AB  - Disuse uncouples bone formation from resorption, leading to increased porosity,
      decreased bone geometrical properties, and decreased bone mineral content which
      compromises bone mechanical properties and increases fracture risk. However,
      black bear bone properties are not adversely affected by aging despite annual
      periods of disuse (i.e., hibernation), which suggests that bears either prevent
      bone loss during disuse or lose bone and subsequently recover it at a faster rate
      than other animals. Here we show decreased cortical bone turnover during
      hibernation with balanced formation and resorption in grizzly bear femurs.
      Hibernating grizzly bear femurs were less porous and more mineralized, and did
      not demonstrate any changes in cortical bone geometry or whole bone mechanical
      properties compared to active grizzly bear femurs. The activation frequency of
      intracortical remodeling was 75% lower during hibernation than during periods of
      physical activity, but the normalized mineral apposition rate was unchanged.
      These data indicate that bone turnover decreases during hibernation, but osteons
      continue to refill at normal rates. There were no changes in regional variation
      of porosity, geometry, or remodeling indices in femurs from hibernating bears,
      indicating that hibernation did not preferentially affect one region of the
      cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone
      turnover and maintaining balanced formation and resorption, which preserves bone
      structure and strength. These results support the idea that bears possess a
      biological mechanism to prevent disuse osteoporosis.

PMID- 18037368
TI  - Site-directed mutagenesis by combination of homologous recombination and DpnI
      digestion of the plasmid template in Escherichia coli.
AB  - A rapid site-directed mutagenesis strategy using homologous recombination and
      DpnI digestion of the template in Escherichia coli is described. Briefly, inverse
      polymerase chain reaction amplification of the entire circular plasmid was
      performed by mutagenic primers with overlapping sequences ( approximately 15 bp)
      for generating PCR products with approximately 15 bp of homology on the terminal
      ends. On direct transformation of the amplified PCR products into restriction
      endonuclease DpnI-expressing E. coli BUNDpnI, homologous recombination occurs in
      E. coli while the original templates are removed via DpnI digestion in vivo, thus
      yielding clones harboring mutated circular plasmids. Nearly 100% efficiency was
      attained when this strategy was used to modify DNA sequences.

PMID- 18037369
TI  - The N-terminus of PrP is responsible for interacting with tubulin and fCJD
      related PrP mutants possess stronger inhibitive effect on microtubule assembly in
      vitro.
AB  - Microtubule dynamics is essential for many vital cellular processes such as in
      intracellular transport, metabolism, and cell division. Some evidences
      demonstrate that PrP may associate with microtubular cytoskeleton and its major
      component, tubulin. In the present study, the molecular interaction between PrP
      and tubulin was confirmed using pull-down assays, immunoprecipitation and ELISA.
      The interacting regions within PrP with tubulin were mapped in the N-terminus of
      PrP spanning residues 23-50 and 51-91. PrP octapeptide repeats are critical for
      the binding activity with tubulin, that the binding activity of PrP with tubulin
      became stronger along with the number of the octapeptide repeats increased.
      Microtubule assembly assays, sedimental tests and transmission electron
      microscopy demonstrated that the full-length PrP (aa 23-231) obviously inhibited
      the microtubule polymerization processes in vitro, whereas the N- (aa 23-91) and
      C- (aa 91-231) terminal peptides of PrP did not affect microtubule
      polymerization. Moreover, the familial Cruetzfeldt Jacob disease (fCJD) related
      PrP mutants with inserted or deleted octapeptide repeats showed much stronger
      inhibitive capacities on the microtubule dynamics in vitro than wild-type PrP.
      Our data highlight a potential role of PrP in regulating the microtubule dynamics
      in neurons.

PMID- 18037370
TI  - Over-expression of angiotensin II type 2 receptor (agtr2) decreases collagen
      accumulation in atherosclerotic plaque.
AB  - Angiotensin (Ang) II, via type 1 receptor activation, exerts a significant role
      in atherogenesis and collagen synthesis. To test the hypothesis that Ang II type
      2 receptor (AT2R) upregulation delivered with adeno-associated virus type 2
      (AAV/AT2R) would inhibit collagen synthesis in atherosclerotic arteries, LDLR
      knockout mice were injected with AAV/AT2R and fed 4% cholesterol diet for 18
      weeks. LDLR knockout mice treated with saline or AAV/Neo exhibited extensive
      vessel wall collagen accumulation, which was reduced by about 50% with AT2R over
      expression. AT2R upregulation completely blocked the alterations in the
      expression of procollagen-I, osteopontin, fibronectin, CD68, and matrix
      metalloproteinases (MMP-2 and MMP-9), as well as phosphorylation of p38 and
      p44/42 MAPKs. Activity of superoxide dismutase was reduced in the LDLR KO mice
      and it increased with AT2R upregulation. This study demonstrates that AT2R over
      expression reduces enhanced collagen accumulation, MMP expression and activity in
      atherosclerotic regions via inhibition of pro-oxidant signals.

PMID- 18037371
TI  - Synergistic induction of MUC5AC mucin by nontypeable Haemophilus influenzae and
      Streptococcus pneumoniae.
AB  - Mucin overproduction is a hallmark of chronic respiratory diseases (CRD) such as
      chronic obstructive pulmonary disease and asthma, and otitis media. Despite the
      fact that nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae
      are co-existing under these disease conditions, little is known about how NTHi
      and S. pneumoniae induce mucin overproduction. Here we show that NTHi and S.
      pneumoniae, when present together, synergistically induce MUC5AC mucin
      transcription. TLR2/4-MyD88-TAK1 signaling cascade transmits signal to regulate
      the synergistic induction of MUC5AC. The activation of MKK3/6-p38 and ERK MAPK
      pathways are required for the synergistic induction of MUC5AC. Moreover, S.
      pneumoniae synergizes with NTHi to induce MUC5AC expression via AP-1-dependent
      mechanism. Thus, our studies provide direct evidence for the synergistic
      induction of MUC5AC in mixed infections and bring novel insights into our
      understanding of molecular mechanisms underlying polymicrobial infections in CRD
      and OM.

PMID- 18037372
TI  - Cd2+ versus Zn2+ uptake by the ZIP8 HCO3--dependent symporter: kinetics,
      electrogenicity and trafficking.
AB  - The mouse Slc39a8 gene encodes the ZIP8 transporter, which has been shown to be a
      divalent cation/HCO3- symporter. Using ZIP8 cRNA-injected Xenopus oocyte
      cultures, we show herein that: [a] ZIP8-mediated cadmium (Cd(2+)) and zinc
      (Zn(2+)) uptake have V(max) values of 1.8+/-0.08 and 1.0+/-0.08 pmol/oocyte/h,
      and K(m) values of 0.48+/-0.08 and 0.26+/-0.09 microM, respectively; [b] ZIP8
      mediated Cd(2+) uptake is most inhibited by Zn(2+), second-best inhibited by
      Cu(2+), Pb(2+) and Hg(2+), and not inhibited by Mn(2+) or Fe(2+); and [c]
      electrogenicity studies demonstrate an influx of two HCO3- anions per one Cd(2+)
      (or one Zn(2+)) cation, i.e. electroneutral complexes. Using Madin-Darby canine
      kidney (MDCK) polarized epithelial cells retrovirally infected with ZIP8 cDNA and
      tagged with hemagglutinin at the C-terminus, we show that-similar to ZIP4-the
      ZIP8 eight-transmembrane protein is largely internalized during Zn(2+)
      homeostasis, but moves predominantly to the cell surface membrane (trafficking)
      under conditions of Zn(2+) depletion.

PMID- 18037373
TI  - Bitter peptides activate hTAS2Rs, the human bitter receptors.
AB  - Fermented food contains numerous peptides derived from material proteins. Bitter
      peptides formed during the fermentation process are responsible for the bitter
      taste of fermented food. We investigated whether human bitter receptors (hTAS2Rs)
      recognize bitterness of peptides with a heterologous expression system. HEK293
      cells expressing hTAS2R1, hTAS2R4, hTAS2R14, and hTAS2R16 responded to bitter
      casein digests. Among those cells, the hTAS2R1-expressing cell was most strongly
      activated by the synthesized bitter peptides Gly-Phe and Gly-Leu, and none of the
      cells was activated by the non-bitter dipeptide Gly-Gly. The results showed that
      these bitter peptides, as well as many other bitter compounds, activate hTAS2Rs,
      suggesting that humans utilize these hTAS2Rs to recognize and perceive the
      structure and bitterness of peptides.

PMID- 18037374
TI  - Simvastatin enhances endothelial differentiation of peripheral blood mononuclear
      cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8
      secretion from monocytes.
AB  - BACKGROUND: Statins are known to have pleiotropic effects. We examined the effect
      and mechanism of simvastatin therapy on EPC differentiation and pro-angiogenic
      cytokines in patients with hypercholesterolemia. METHODS: Twenty-two
      hypercholesterolemia patients without any other modifiable cardiovascular risk
      factors or history of previous lipid-lowering therapy were given simvastatin 20
      mg/day for 4 weeks. Blood were drawn pre- and post-therapy. The in vitro effects
      of simvastatin were studied in a separate set of experiments. RESULTS:
      Simvastatin treatment significantly increased the number of DiI-acLDL, UEA-1
      lectin double-positive EPCs and facilitated its appearance. By FACS analysis of
      freshly isolated PBMNCs, KDR (+) cells increased after simvastatin treatment
      while there were no differences in CD34, AC133, and VE-cadherin. Also, serum
      concentration of IL-8 was markedly increased, while VEGF was only slightly
      increased. In vitro, PBMNCs co-cultured with simvastatin showed increased cluster
      formation at day 7, and simvastatin facilitated the appearance and networking of
      EPCs compared with vehicle. Simvastatin-co-cultured PBMNCs showed significantly
      increased KDR (+) cells, in contrast to CD34, CD31, and VE-Cadherin (+) cells. In
      response to simvastatin, IL-8 was mainly increased in monocyte culture
      supernatants while VEGF increased in smooth muscle cell culture supernatants.
      These cytokines were associated with increased EPC migratory function. The
      increase in IL-8 secretion from monocytes by statin treatment was associated with
      phosphorylation and inactivation of GSK3beta, which was reversed by constitutive
      activation of GSK-3beta. CONCLUSION: Simvastatin enhances endothelial
      differentiation of peripheral blood mononuclear cells in patients with
      hypercholesterolemia and increases pro-angiogenic cytokine IL-8 secretion from
      monocytes. Our results may explain the pro-angiogenic effects associated with
      statin therapy and offer further evidence of statin pleiotropism.

PMID- 18037375
TI  - Developmental silencing and independency from E2F of apoptotic gene expression in
      postmitotic tissues.
AB  - The involvement of caspases in postmitotic cell death is controversial. Here we
      report that adult brain and heart are devoid of many key pro-apoptotic proteins
      due to a progressive postnatal silencing event involving a reduction of their
      transcript levels. E2F has been shown to control cell cycle progression and to be
      transcriptional activator of apoptotic genes. However, our data demonstrate that
      apoptotic gene expression in heart, brain and liver, as well as cardiac and
      neuronal apoptotic gene silencing during development, are E2F-independent events.
      Therefore, the genes regulating caspase-dependent cell death are expressed in
      embryonic organs in an E2F-independent manner and a developmental-related
      silencing event represses these genes in postmitotic adult tissues.

PMID- 18037377
TI  - Reversible dissociation of flavin mononucleotide from the mammalian membrane
      bound NADH: ubiquinone oxidoreductase (complex I).
AB  - Conditions for the reversible dissociation of flavin mononucleotide (FMN) from
      the membrane-bound mitochondrial NADH:ubiquinone oxidoreductase (complex I) are
      described. The catalytic activities of the enzyme, i.e. rotenone-insensitive
      NADH:hexaammineruthenium III reductase and rotenone-sensitive NADH:quinone
      reductase decline when bovine heart submitochondrial particles are incubated with
      NADH in the presence of rotenone or cyanide at alkaline pH. FMN protects and
      fully restores the NADH-induced inactivation whereas riboflavin and flavin
      adenine dinucleotide do not. The data show that the reduction of complex I
      significantly weakens the binding of FMN to protein thus resulting in its
      dissociation when the concentration of holoenzyme is comparable with K(d (
      approximately 10(-8)M at pH 10.0).

PMID- 18037378
TI  - A novel ferritin gene, SferH-5, reveals heterogeneity of the 26.5-kDa subunit of
      soybean (Glycine max) seed ferritin.
AB  - A novel ferritin cDNA, SferH-5, has been cloned from 7-day-old soybean seedlings.
      Putative SferH-5 has 96% identity with SferH-1 reported previously. All the five
      amino acid variants distributed in the mature region are not involved in highly
      conserved residues associated with ferroxidase activity center. We speculate that
      SferH-5 encodes a novel 26.5-kDa subunit of soybean seed ferritin, which is
      designated H-5 in this study. Recombinant H-5 was able to assemble, together with
      co-expressed H-2, as a functional soybean seed ferritin-like complex, H-5/H-2.
      Our data reveal the potential heterogeneity of the 26.5-kDa subunit of soybean
      seed ferritin.

PMID- 18037379
TI  - The heterotrimeric [corrected] G protein subunit G alpha i is present on
      mitochondria.
AB  - Receptors that signal through heterotrimeric [corrected] GTP binding (G) proteins
      mediate the majority of intercellular communication. Recent evidence suggests
      that receptors acting through G proteins also transfer signals across the nuclear
      membrane. Here we present cell fractionation and immunolabeling data showing that
      the heterotrimeric [corrected] G protein subunit Galphai is associated with
      mitochondria. This finding suggests that G protein receptor signaling may be a
      feature common to all membranes.

PMID- 18037380
TI  - A soluble and active form of Wnt-3a protein is involved in myogenic
      differentiation after cholesterol depletion.
AB  - Cholesterol is one of the major lipids of plasma membranes. Recently, we have
      shown that cholesterol depletion by methyl-beta-cyclodextrin (M beta CD) induces
      the activation of the Wnt/beta-catenin pathway and enhances myogenic
      differentiation. Here, we show that M beta CD-conditioned media accelerates
      myogenesis in a similar way as M beta CD does, suggesting that the effects
      induced by M beta CD could be caused by soluble factors present in the culture
      medium. Soluble Wnt-3 protein is significantly enhanced in M beta CD-conditioned
      medium. Wnt-3a-enriched media induces myogenesis as much as M beta CD does,
      whereas Wnt-5a-enriched media inhibits. We suggest that Wnt-3a is involved in the
      myogenic induction observed after cholesterol depletion.

PMID- 18037376
TI  - TNF-alpha and adipocyte biology.
AB  - Dyslipidemia and insulin resistance are commonly associated with catabolic or
      lipodystrophic conditions (such as cancer and sepsis) and with pathological
      states of nutritional overload (such as obesity-related type 2 diabetes). Two
      common features of these metabolic disorders are adipose tissue dysfunction and
      elevated levels of tumour necrosis factor-alpha (TNF-alpha). Herein, we review
      the multiple actions of this pro-inflammatory adipokine on adipose tissue
      biology. These include inhibition of carbohydrate metabolism, lipogenesis,
      adipogenesis and thermogenesis and stimulation of lipolysis. TNF-alpha can also
      impact the endocrine functions of adipose tissue. Taken together, TNF-alpha
      contributes to metabolic dysregulation by impairing both adipose tissue function
      and its ability to store excess fuel. The molecular mechanisms that underlie
      these actions are discussed.

PMID- 18037382
TI  - Different functional classes of genes are characterized by different
      compositional properties.
AB  - A compositional analysis on a set of human genes classified in several functional
      classes was performed. We found out that the GC3, i.e. the GC level at the third
      codon positions, of the genes involved in cellular metabolism was significantly
      higher than those involved in information storage and processing. Analyses of
      human/Xenopus ortologous genes showed that: (i) the GC3 increment of the genes
      involved in cellular metabolism was significantly higher than those involved in
      information storage and processing; and (ii) a strong correlation between the GC3
      and the corresponding GCi, i.e. the GC level of introns, was found in each
      functional class. The non-randomness of the GC increments favours the selective
      hypothesis of gene/genome evolution.

PMID- 18037381
TI  - Long and short isoforms of Neurospora clock protein FRQ support temperature
      compensated circadian rhythms.
AB  - The large (l) and small (s) isoforms of FREQUENCY (FRQ) are elements of
      interconnected feedback loops of the Neurospora circadian clock. The expression
      ratio of l-FRQ vs. s-FRQ is regulated by thermosensitive splicing of an intron
      containing the initiation codon for l-FRQ. We show that this splicing is
      dependent on light and temperature and displays a circadian rhythm. Strains
      expressing only l-FRQ or s-FRQ support short and long temperature-compensated
      circadian rhythms, respectively. The thermosensitive expression ratio of FRQ
      isoforms influences period length in wt. Our data indicate that differential
      expression of FRQ isoforms is not required for temperature compensation but
      rather provides a means to fine-tune period length in response to ambient
      temperature.

PMID- 18037383
TI  - Histidine residues in the IS3-IS4 loop are critical for nickel-sensitive
      inhibition of the Cav2.3 calcium channel.
AB  - We recently reported that a histidine (H191) in the S3-S4 loop of domain I is
      critical for nickel inhibition of the Cav3.2 T-type Ca2+ channel. As in Cav3.2,
      two histidine residues are commonly found in the IS3-IS4 loops of mammalian
      Cav2.3 Ca2+ channels, which are also blocked by low micromolar concentrations of
      nickel. We show here by site-directed mutagenesis and electrophysiology that both
      residues contribute to the nickel sensitivity of Cav2.3, with H183 being more
      critical than H179. These findings strongly suggest that both H179 and H183 in
      the IS3-IS4 loop are essential structural determinants required for nickel
      sensitive inhibition of the Cav2.3.

PMID- 18037384
TI  - Heparin enhances the furin cleavage of HIV-1 gp160 peptides.
AB  - Infectious HIV-1 requires gp160 cleavage by furin at the REKR511 downward arrow
      motif (site1) into the gp120/gp41 complex, whereas the KAKR503 (site2) sequence
      remains uncleaved. We synthesized 41mer and 51mer peptides, comprising site1 and
      site2, to study their conformation and in vitro furin processing. We found that,
      while the previously reported 19mer and 13mer analogues represent excellent in
      vitro furin substrates, the present extended sequences require heparin for
      optimal processing. Our data support the hypothesis of a direct binding of
      heparin with site1 and site2, allowing selective exposure/accessibility of the
      REKR sequence, which is only then optimally cleaved by furin.

PMID- 18037385
TI  - Comparative codon and amino acid composition analysis of Tritryps-conspicuous
      features of Leishmania major.
AB  - Comparative analyses of codon/amino acid usage in Leishmania major, Trypanosoma
      brucei and Trypanosoma cruzi reveal that gene expressivity and GC-bias play key
      roles in shaping the gene composition of all three parasites, and protein
      composition of L. major only. In T. brucei and T. cruzi, the major contributors
      to the variation in protein composition are hydropathy and/or aromaticity.
      Principle of Cost Minimization is followed by T. brucei, disregarded by T. cruzi
      and opposed by L. major. Slowly evolving highly expressed gene-products of L.
      major bear signatures of relatively AT-rich ancestor, while faster evolution
      under GC-bias has characterized the lowly expressed genes of the species by
      higher GC12-content.

PMID- 18037386
TI  - Saccharomyces cerevisiae phospholipid:diacylglycerol acyl transferase (PDAT)
      devoid of its membrane anchor region is a soluble and active enzyme retaining its
      substrate specificities.
AB  - A N-terminal deleted version of the Saccharomyces cerevisiae
      phospholipid:diacylglycerol acyltransferase (ScPDAT), lacking the predicted
      membrane-spanning region, was fused in frame with alpha-factor secretion signal
      and expressed in Pichia pastoris under the control of the methanol inducible
      alcohol oxidase promoter. This resulted in a truncated, soluble and highly active
      PDAT protein secreted into the culture medium of the recombinant cells. The
      soluble as well as native membrane bound enzymes was shown to be glycosylated and
      extensive deglycosylation severely lowered the activity. The production of a
      soluble and extracellular PDAT allowed us to investigate substrate preferences of
      the enzyme without interference of endogenous lipids and enzymes. Similar to the
      membrane bound counterpart, the highest activity was achieved with acyl groups at
      sn-2 position of phosphatidylethanolamine as acyl donor and 1,2-diacylglycerols
      as acyl acceptor. The soluble enzyme was also able to catalyze, at a low rate, a
      number of transacylation reactions between various neutral lipids and between
      polar lipids and neutral lipids others than diacylglycerols, including acylation
      of long chain alcohols.

PMID- 18037387
TI  - Special issue: inhibitors of protein kinases.

PMID- 18037388
TI  - Thermal stimulation causes tooth deformation: a possible alternative to the
      hydrodynamic theory?
AB  - OBJECTIVES: To investigate the relationship between temperature distribution and
      tooth structure deformation during and after localised application of thermal
      stimuli used during pulp vitality testing. METHODS: Strains and temperature
      changes within tooth structures were recorded when three different thermal
      stimuli, namely heated gutta percha (120-140 degrees C), carbon dioxide dry ice (
      72 degrees C) and refrigerant spray (-50 degrees C), were applied to extracted
      bovine incisors. Each stimulus was applied for 5s on the labial enamel surface in
      a random order, with a 30-min interval between tests. Finite element analysis was
      performed on basic geometrical shapes to investigate structural deformation in
      relation to temperature change. RESULTS: Application of thermal stimuli to the
      labial enamel surface resulted in rapid development of strain at the pulpal
      dentine surface before any temperature change was detected at the dentino-enamel
      junction. The strain pattern was biphasic; heat produced an initial contraction
      of the pulpal surface, followed by an expansion, and the reverse pattern was
      found with cold stimulation. Finite element analysis confirmed that the initially
      pronounced thermal gradient across the enamel and dentine caused rapid flexural
      deformation before temperature changes reached the dentino-enamel junction. When
      the temperature changes reached the pulpal dentine and thus reduced the thermal
      gradient, the direction of the strain was reversed. CONCLUSION: These results
      indicate possible alternatives to the hydrodynamic theory for thermal stimuli
      applied to intact teeth. Mechanically induced dentine deformation may trigger
      nerve impulses directly, or may exert mechanically induced dentinal fluid flow
      that triggers nerve activity.

PMID- 18037390
TI  - Imagery about suicide in depression--"Flash-forwards"?
AB  - Suicide is a significant world health problem, with more deaths by suicide
      globally than by war. We need to better understand the cognitive processes
      underlying suicidal thinking for improved treatment development. Cognitive
      psychology indicates that mental imagery can be causal in determining future
      behavior, yet the occurrence of suicide-related imagery has not previously been
      investigated. Interviews with 15 depressed and formerly suicidal patients in
      remission found that all patients reported experiencing detailed mental imagery
      in addition to verbal thoughts when at their most despairing, for example images
      of making a future suicide attempt. A clinical measure of the severity of
      suicidal ideation was associated with both preoccupation with suicide-related
      imagery and perceived imagery realness. Echoing flashbacks in posttraumatic
      stress disorder, the current images appeared like "flash-forwards" to suicide.
      These results provide the first data to our knowledge on the existence of mental
      imagery in suicidality, opening a promising new avenue for research.

PMID- 18037391
TI  - Imagery rescripting and reprocessing therapy after failed prolonged exposure for
      post-traumatic stress disorder following industrial injury.
AB  - Prolonged exposure (PE) has been reported to be effective for improving post
      traumatic stress symptoms in 60-65% of trauma victims suffering from post
      traumatic stress disorder (PTSD). This study examined the results of adding an
      imagery-based, cognitive restructuring component (imagery rescripting and
      reprocessing therapy, IRRT) to the treatment of 23 Type I trauma victims
      suffering from PTSD, all of whom failed to improve with PE alone. With the added
      treatment component, 18 of 23 clients showed a full recovery from their PTSD
      symptoms, and no longer met criteria for PTSD after 1-3 sessions of IRRT. It was
      noteworthy that non-FEAR emotions (e.g., guilt, shame, anger) were found to be
      predominant for all 23 PE failures examined in this study, suggesting that a
      simple habituation model (on which PE is based) is not sufficient to address non
      FEAR emotions in PTSD. By contrast, IRRT, a cognitive restructuring treatment,
      was much more effective in PTSD symptom reduction for these clients. It was
      proposed that more detailed, individualized trauma assessments be conducted for
      each patient that focus on (1) identifying the predominant trauma-related
      emotions and cognitions that maintain the PTSD response, and (2) finding the best
      CBT "treatment fit" for the specific trauma characteristics of each patient.

PMID- 18037392
TI  - Perceptual and conceptual processing as predictors of treatment outcome in PTSD.
AB  - Cognitive behavioural treatment (CBT) is highly effective in treating post
      traumatic stress disorder (PTSD). However, the mechanisms of change are still
      poorly understood. The aim of the present study was to investigate trauma
      processing during and after CBT for PTSD. Treatment consisted of imaginal
      exposure combined with rescripting. The rationale of this treatment is that
      dysfunctional interpretations may best be corrected by inducing new perspectives
      on what happened during trauma by experiencing new views and new emotions. In
      twenty-five chronic patients with PTSD, we tested whether an initial increase of
      perceptual processing and a subsequent increase of conceptual processing
      predicted treatment outcome. Possible changes in perceptual/conceptual processing
      during and after treatment were inferred from changes in trauma memories from pre
      to post-treatment and from post- to 1-month follow-up. These memory parameters
      were assessed by analysing trauma narratives that were produced before the first
      treatment session, after the last treatment session and at follow-up. Consistent
      with predictions, a relative increase of conceptual processing after treatment
      predicted treatment outcome levels for both PTSD symptoms and general
      psychopathology at 1-month follow-up. Although a relative increase of perceptual
      processing during treatment also predicted treatment outcome, this effect was
      explained by the beneficial effect of a subsequent increase of conceptual
      processing. But an increase of perceptual processing during treatment was
      strongly related to an increase of conceptual processing after treatment. The
      results suggest that imaginal reliving during CBT is not crucial for symptom
      reduction, but it may promote conceptual processing, which in itself predicts a
      better treatment outcome.

PMID- 18037393
TI  - Na+/Ca2+ exchanger subtype (NCX1, NCX2, NCX3) protein expression in the rat
      hippocampus following 3 min and 8 min durations of global cerebral ischemia.
AB  - There is increasing evidence that the sodium-calcium exchanger (NCX) subtypes,
      NCX1, NCX2 and NCX3 play an important role in intracellular calcium
      homeostasis/dysregulation following cerebral ischemia. In the present study we
      examined NCX1, NCX2 and NCX3 protein levels in the rat hippocampus at 3, 6, 12,
      18, 24 and 48 h following a 3 min and 8 min duration of global cerebral ischemia.
      We observed that NCX1 protein levels were significantly increased by 22.3% and
      20.6% at the 6 and 12 h respective time points following a 3 min duration of
      global ischemia, while NCX2 and NCX3 protein levels remained relatively constant.
      Following a 8 min duration of global ischemia, NCX1 protein levels remained
      relatively constant, while NCX2 protein levels were down-regulated by 6.9%,
      10.8%, 14.4% and 10.3% at the 6, 18, 24 and 48 h respective time points, and NCX3
      protein levels were up-regulated by 22.1% at the 18 h time point. Taken together,
      our results show that NCX subtype protein expression is sensitive to cerebral
      ischemia, and indicates that changes in NCX activity may be playing an important
      role in calcium maintenance and neuronal outcome following ischemia.

PMID- 18037394
TI  - Activation of ERK in the rostral ventromedial medulla is involved in hyperalgesia
      during peripheral inflammation.
AB  - We have previously shown that the extracellular signal-regulated kinase (ERK) is
      activated in the rostral ventromedial medulla (RVM) during peripheral
      inflammation. In the present study, the relationship between ERK signaling in the
      RVM and pain hypersensitivity was investigated in the rat. Microinjection of
      U0126, a mitogen-activated protein kinase kinase inhibitor, into the RVM
      decreased phosphorylated ERK at 7 h after complete Freund's adjuvant (CFA)
      injection into the hindpaw. The U0126 microinjection also attenuated thermal
      hyperalgesia in the ipsilateral hindpaw at 24 h after CFA injection. The
      ipsilateral paw withdrawal latency in the U0126 group (67.9%+/-5.3% vs. baseline,
      n=7) was significantly longer than that in the control group (52.0%+/-3.6% vs.
      baseline, n=8). These findings suggest that activation of ERK in the RVM
      contributes to thermal hyperalgesia during peripheral inflammation.

PMID- 18037395
TI  - Computerized heart sounds analysis.
AB  - This paper is concerned with a synthesis study of the fast Fourier transform
      (FFT), the short-time Fourier transform (STFT), the Wigner distribution (WD) and
      the wavelet transform (WT) in analysing the phonocardiogram signal (PCG). It is
      shown that these transforms provide enough features of the PCG signals that will
      help clinics to obtain qualitative and quantitative measurements of the time
      frequency (TF) PCG signal characteristics and consequently aid diagnosis.
      Similarly, it is shown that the frequency content of such a signal can be
      determined by the FFT without difficulties. The studied techniques (FT, STFT, WD,
      CWT, DWT and PWT) of analysis can thus be regarded as complementary in the TF
      analysis of the PCG signal; each will relate to a part distinct from the analysis
      in question.

PMID- 18037396
TI  - Comments on "optimization and parallelization strategies for Monte Carlo
      simulation of HIV infection" by D. Hecquet, H.J. Ruskin and M. Crane. Computers
      in Biology and Medicine, vol. 37, 691, 2007.

PMID- 18037397
TI  - Overexpression of PPK-1, the Caenorhabditis elegans Type I PIP kinase, inhibits
      growth cone collapse in the developing nervous system and causes axonal
      degeneration in adults.
AB  - Growth cones are dynamic membrane structures that migrate to target tissue by
      rearranging their cytoskeleton in response to environmental cues. The lipid
      phosphatidylinositol (4,5) bisphosphate (PIP(2)) resides on the plasma membrane
      of all eukaryotic cells and is thought to be required for actin cytoskeleton
      rearrangements. Thus PIP(2) is likely to play a role during neuron development,
      but this has never been tested in vivo. In this study, we have characterized the
      PIP(2) synthesizing enzyme Type I PIP kinase (ppk-1) in Caenorhabditis elegans.
      PPK-1 is strongly expressed in the nervous system, and can localize to the plasma
      membrane. We show that PPK-1 purified from C. elegans can generate PIP(2)in vitro
      and that overexpression of the kinase causes an increase in PIP(2) levels in
      vivo. In developing neurons, PPK-1 overexpression leads to growth cones that
      become stalled, produce ectopic membrane projections, and branched axons. Once
      neurons are established, PPK-1 overexpression results in progressive membrane
      overgrowth and degeneration during adulthood. These data suggest that
      overexpression of the Type I PIP kinase inhibits growth cone collapse, and that
      regulation of PIP(2) levels in established neurons may be important to maintain
      structural integrity and prevent neuronal degeneration.

PMID- 18037399
TI  - The zebrafish cerebellar rhombic lip is spatially patterned in producing granule
      cell populations of different functional compartments.
AB  - The upper rhombic lip, a prominent germinal zone of the cerebellum, was recently
      demonstrated to generate different neuronal cell types over time from spatial
      subdomains. We have characterized the differentiation of the upper rhombic lip
      derived granule cell population in stable GFP-transgenic zebrafish in the context
      of zebrafish cerebellar morphogenesis. Time-lapse analysis followed by individual
      granule cell tracing demonstrates that the zebrafish upper rhombic lip is
      spatially patterned along its mediolateral axis producing different granule cell
      populations simultaneously. Time-lapse recordings of parallel fiber projections
      and retrograde labeling reveal that spatial patterning within the rhombic lip
      corresponds to granule cells of two different functional compartments of the
      mature cerebellum: the eminentia granularis and the corpus cerebelli. These
      cerebellar compartments in teleosts correspond to the mammalian
      vestibulocerebellar and non-vestibulocerebellar system serving balance and
      locomotion control, respectively. Given the high conservation of cerebellar
      development in vertebrates, spatial partitioning of the mammalian granule cell
      population and their corresponding earlier-produced deep nuclei by patterning
      within the rhombic lip may also delineate distinct functional compartments of the
      cerebellum. Thus, our findings offer an explanation for how specific functional
      cerebellar circuitries are laid down by spatio-temporal patterning of cerebellar
      germinal zones during early brain development.

PMID- 18037400
TI  - Involvement of serotonin receptors 5-HT1 and 5-HT2 in 12(S)-HPETE-induced
      scratching in mice.
AB  - The mechanisms of 12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid (12(S)
      HPETE)-induced scratching were studied in ICR mice. In a recent paper, we
      demonstrated that the 12(S)-HPETE-induced scratching was reduced not by U75302
      (BLT(1) receptor antagonist), but by LY255283 (BLT(2) receptor antagonist). In
      the present study, we tested various compounds to elucidate the mechanism of
      12(S)-HPETE-induced scratching relating to transient receptor potential vanilloid
      type-1 (TRPV1), histamine receptor (H(1)) and several serotonin receptors (5
      HT(1), 5-HT(2), and 5-HT(3)). As a result, 12(S)-HPETE-induced scratching was
      suppressed by capsaicin (TRPV1 receptor agonist), but not by capsazepine (TRPV1
      receptor antagonist). Additionally, chlopheniramine (H(1) receptor antagonist)
      did not suppress 12(S)-HPETE-induced scratching, but cyproheptadine (H(1)
      receptor and serotonin 5-HT(2) receptor antagonist) potently suppressed the same
      response. Therefore, we tested several serotonin receptor antagonists to explain
      the detailed mechanisms relating to serotonin receptors. The scratching was
      reduced by WAY100635 (5-HT(1) receptor antagonist), or ketanserin (5-HT(2)
      receptor antagonist), but not by ondansetron (5-HT(3) receptor antagonist), after
      intradermal injection of 12(S)-HPETE. These results suggest that serotonin 5
      HT(1/2) receptors are implicated in 12(S)-HPETE-induced scratching in ICR mice
      and that the TRPV1 receptor might not be directly related to 12(S)-HPETE-induced
      scratching.

PMID- 18037398
TI  - Mechanisms underlying pituitary hypoplasia and failed cell specification in Lhx3
      deficient mice.
AB  - The LIM homeodomain transcription factor, LHX3, is essential for pituitary
      development in mouse and man. Lhx3 engineered null mice have profound pituitary
      hypoplasia that we find is attributable to an increase in cell death early in
      pituitary development. Dying cells are localized to regions of TPIT expression
      indicating that cell death may contribute to the severe reduction in
      differentiated corticotrope cells and lower expression of the corticotrope
      transcription factors, TPIT and NEUROD1. Lhx3 deficiency also results in dorsal
      ectopic expression of transcription factors characteristic of gonadotropes, SF1
      and ISL1, but no gonadotropin expression. This apparent disturbance of cell
      differentiation may be due, in part, to loss of NOTCH2. NOTCH2 is normally
      expressed in the pituitary at the boundary between dorsal, proliferating cells
      and ventral, differentiating cells and is important for maintaining dorsal
      ventral patterning in other organs. Thus, Lhx3 contributes significantly to
      pituitary development by maintaining normal dorsal-ventral patterning, cell
      survival, and normal expression of corticotrope-specific transcription factors,
      which are necessary for repressing ectopic gonadotrope differentiation.

PMID- 18037402
TI  - The effects on hTERT gene expression is an additional mechanism of amino
      bisphosphonates in prostatic cancer cells.
AB  - Many studies have demonstrated various effects of bisphosphonates on several
      cancer cells and it is accepted that their anti-tumor activity is related to
      interference with the mevalonate pathway. In addition, it is well known that gene
      expression of hTERT, the catalytic subunit of the telomerase, is elevated in
      prostatic cancer. In the prostate cancer cell lines we investigated the effects
      on hTERT gene expression of several bisphosphonates. We also evaluated whether
      the observed levels of expression were affected by the exposure to an analogue of
      the geranylgeranylpyrophosphate, the geranylgeraniol used to recover the
      mevalonate pathway. Our results showed that the amino-bisphosphonates down
      regulate hTERT gene expression and that combined treatment with geranylgeraniol
      and zoledronate was able to revert only partially the effects on viability; on
      the contrary, hTERT gene down-regulation was not affected by the restoration of
      the mevalonate pathway. These results support the hypothesis that prostatic
      cancer cells are targeted by amino-bisphosphonates also through a different
      mechanism from the mevalonate pathway.

PMID- 18037401
TI  - Comparison of the induction of P-glycoprotein activity by nucleotide, nucleoside,
      and non-nucleoside reverse transcriptase inhibitors.
AB  - Combination therapy against human immunodeficiency virus (HIV)-infection is
      complicated by drug-drug interactions between antiretrovirals and also between
      anti-HIV drugs and drugs used to treat co-morbidity. P-glycoprotein represents
      one important site for drug interactions and induction of its function could
      reduce the effectiveness of drugs that are P-glycoprotein substrates. We
      therefore investigated induction of P-glycoprotein function in LS180 cells by non
      nucleoside and nucleoside reverse transcriptase inhibitors (NNRTIs and NRTIs) and
      tenofovir as essential components of antiretroviral combination therapy. P
      glycoprotein activity was increased by all NNRTIs and some NRTIs with delavirdine
      (5.3-fold at 100 muM) having the largest effect.

PMID- 18037403
TI  - Role of Ca2+-sensitization in attenuated carbachol-induced contraction of the
      colon in a rat model of colitis.
AB  - Inflammatory bowel disease is associated with reduced colonic smooth muscle
      contractility. However the underlying mechanism responsible for the decrease in
      contractility is not fully understood. In this study we investigated the role of
      Ca(2+)-sensitization in reduced carbachol-induced contraction of colonic segments
      from rats treated with trinitrobenzenesulphonic acid (TNBS). Functional
      alterations in RhoA/Rho-kinase and protein kinase C (PKC) pathways were examined
      using specific antagonists, Y-27632 and GF-109203X respectively. In this study,
      TNBS-induced colitis was associated with a decrease in the maximum response but
      not sensitivity to carbachol. Permeabilized inflamed colonic segments showed
      greater sensitivity to Ca(2+) as compared to controls, indicating greater Ca(2+)
      sensitivity of the myofilaments. In contrast, carbachol-induced increase in
      Ca(2+)-sensitization was reduced in these tissues suggesting that the reduced
      carbachol-induced contraction could be due to decreased Ca(2+)-sensitization. Y
      27632, a Rho-kinase inhibitor, induced significantly greater relaxation in colon
      strips from TNBS-treated rats indicating higher basal tone in these tissues. This
      is consistent with increased expression of Rho-kinase in the inflamed colon. Y
      27632 concentration-dependently inhibited carbachol-induced contractions in
      control and TNBS-treated rats. However its effect was not significantly different
      between the two groups. GF-109203X, a PKC antagonist, produced concentration
      dependent reduction in carbachol-induced contractions in control and TNBS-treated
      rats. GF-109203X was less effective in reducing carbachol-induced contractions of
      colonic segments from TNBS-treated rats suggesting a defect in PKC activation.
      Western blotting analysis showed reduced expression of total PKC in inflamed
      colonic smooth muscle. Carbachol-induced phosphorylation of CPI-17 was also
      reduced in colonic segments from TNBS-treated rats. These findings suggest that
      Ca(2+)-sensitization in rat colon involves both the PKC and the Rho-kinase
      pathways and that the reduced carbachol-induced contraction in colitis was due to
      inflammation-induced changes in Ca(2+)-sensitization involving a defect in the
      PKC pathway.

PMID- 18037404
TI  - Distinctive role of central histamine H3 receptor in various orexigenic pathways.
AB  - Despite the well-established role of histamine as an anorexigenic
      neurotransmitter, the role of histamine H(3) receptors in feeding behavior is
      controversial. Herein we investigated the role of histamine H(3) receptor on
      several orexigenic agents in mice. Thioperamide (histamine H(3) receptor inverse
      agonist) inhibited neuropeptide Y- and nociceptin-induced hyperphagia but had no
      effect on U-50488 (opioid kappa-receptor agonist)-induced hyperphagia. In
      contrast, imetit (histamine H(3) receptor agonist) inhibited U-50488-induced
      hyperphagia but augmented neuropeptide Y-induced hyperphagia while it did not
      alter nociceptin-induced hyperphagia. These results indicate distinctive roles of
      histamine H(3) receptors in various orexigenic pathways.

PMID- 18037405
TI  - Foundations in cancer research. The turns of life and science.
AB  - This chapter provides a personal insight into the scientific and social
      atmosphere in former Czechoslovakia. It covers the period of the rise of Hasek's
      immunologic school and application of immunologic tolerance to Rous sarcoma virus
      (RSV) heterotransmission. These approaches permitted establishment of a new model
      of mammalian cells transformed by RSV (virogenic XC cells), where the
      noninfectious viral genome was kept indefinitely as new genetic information
      (provirus). RSV was rescued from nonpermissive mammalian cells by fusion
      (complementation) with permissive chicken fibroblasts; this opened the way to
      understanding virus nonpermissiveness. Mammalian cells transformed by the reverse
      transcript of v-src mRNA were characterized, and the resulting provirus was shown
      to be highly oncogenic for chickens and to carry tumor-specific transplantation
      antigen. Other areas covering epigenetic reversion of RSV-transformed cells and
      long-term persistence of chicken leucosis viruses in foreign avian species are
      discussed.

PMID- 18037406
TI  - RUNX genes in development and cancer: regulation of viral gene expression and the
      discovery of RUNX family genes.
AB  - Mouse embryonal carcinoma (EC) cells, also called teratocarcinoma stem cells, are
      nonpermissive for polyomavirus growth, whereas differentiated derivatives of the
      cells are permissive. Mutant viruses capable of growing in EC cells can be
      isolated. They have genomic alterations within the viral enhancer, which is
      required for viral gene expression and DNA replication. This viral regulatory
      region was considered as a potential probe for mouse cell differentiation. The 24
      bp-long A element within the enhancer was identified as a minimum element, which
      also shows a lower activity in EC cells compared with the differentiated cells.
      Transcription factors PEA1/AP1, PEA2/PEBP2, and PEA3/ETS were identified as A
      element-binding proteins. All of them are absent in EC cells and induced to be
      expressed when the cells are differentiated. Although PEBP2 has a weaker
      transactivation activity compared with other two, it is essential for the
      enhancer function of the A element. Purification and cDNA cloning revealed that
      PEBP2 has two subunits, DNA-binding alpha (PEBP2alpha) and non-DNA-binding beta
      (PEBP2beta). PEBP2alpha was found to be highly homologous to a Drosophila
      segmentation gene, runt, and a human gene AML1 that was identified as a part of
      the fusion gene, AML1/ETO (MTG8) generated by t(8;21) chromosome translocation
      associated with acute myelogenous leukemia (AML). Core-binding factor (CBF),
      which interacts with a murine retrovirus enhancer, was found to be identical to
      PEBP2. runt, PEBP2alpha and AML1 are now termed RUNX family, which are involved
      in cell specification during development. There are three mammalian RUNX genes,
      RUNX1, RUNX2, and RUNX3. RUNX1 is essential for generation of hematopoietic stem
      cells and is involved in human leukemia. RUNX2 is essential for skeletal
      development and has an oncogenic potential. RUNX3 is expressed in wider ranges of
      tissues and has multiple roles. Among others, RUNX3 is a major tumor suppressor
      of gastric and many other solid tumors.

PMID- 18037407
TI  - The RNA continent.
AB  - Recent progress in the analyses of the mouse transcriptome leads to unexpected
      discoveries. The mouse genomic sequences read by RNA polymerase II may be six
      times more than previously expected for human chromosomes. The transcript
      abundant regions (named "transcription forests") occupy more than half of the
      genomic sequence and are divided by transcript-scarce regions (transcription
      deserts). Many of the coding mRNAs may have partially overlapping antisense RNAs.
      There are transcripts bridging several adjacent genes that were previously
      regarded as distinct ones. The transcription start sites appearing as cap
      analysis of gene expression (CAGE) tags are mapped on the mouse genomic
      sequences. Distributions of CAGE tags show that the shapes of mammalian gene
      promoters can be classified into four major categories. These shapes were
      conserved between mouse and human. Most of the gene has exonic transcription
      start sites, especially in the 3' untranslated region (3' UTR) sequences. The
      term "RNA continent" has been invented to express this unexpectedly complex and
      prodigious mouse transcriptome. More than a half of the RNA polymerase II
      transcripts are regarded as noncoding RNAs (ncRNAs). The great variety of ncRNAs
      in mammalian transcriptome implies that there are many functional ncRNAs in the
      cells. Especially, the evolutionarily conserved microRNAs play critical roles in
      mammalian development and other biological functions. Moreover, many other ncRNAs
      have also been shown to have biological significant functions, mainly in the
      regulation of gene expression. The functional survey of the RNA continent has
      just started. We will describe the state of the art of the RNA continent and its
      impact on the modern molecular biology, especially on the cancer research.

PMID- 18037408
TI  - The c-myc promoter: still MysterY and challenge.
AB  - The transcription factor c-Myc is a key regulator of cell proliferation, cell
      growth, differentiation, and apoptosis. Deregulated c-myc expression possesses a
      high transformation potential and the proto-oncogene c-myc represents a promising
      target in anticancer therapy. This review on the c-myc promoter describes its
      organization, the different levels of its normal regulation (including initiation
      and elongation of transcription, the dual P1/P2 promoters, chromatin structure, c
      Myc autosuppression) as well as its deregulation in Burkitt's lymphoma.
      Furthermore, it summarizes the many different transcription factors, signal
      transduction pathways, and feedback loops that activate or repress c-myc
      transcription. Finally, a concept for regulation of the c-myc promoter in
      different biological settings, for example, immediate-early induction, constant
      expression throughout the cell cycle in continuously cycling cells, repression
      during terminal differentiation and deregulation in cancer, is formulated.

PMID- 18037409
TI  - Designer self-assembling Peptide nanofiber scaffolds for study of 3-d cell
      biology and beyond.
AB  - Biomedical researchers have become increasingly aware of the limitations of the
      conventional 2-D tissue cell cultures where most tissue cell studies including
      cancer and tumor cells have been carried out. They are now searching and testing
      3-D cell culture systems, something between a petri dish and a mouse. The
      important implications of 3-D tissue cell cultures for basic cell biology, tumor
      biology, high-content drug screening, and regenerative medicine and beyond are
      far-reaching. How can nanobiotechnology truly advance the traditional cell,
      tumor, and cancer biology? Why nano is important in biomedical research and
      medical science? A nanometer is 1000 times smaller than a micrometer, but why it
      matters in biology? This chapter addresses these questions. It has become more
      and more apparent that 3-D cell culture offers a more realistic local environment
      through the nanofiber scaffolds where the functional properties of cells can be
      observed and manipulated. A new class of designer self-assembling peptide
      nanofiber scaffolds now provides an ideal alternative system. Time has come to
      address the 3-D questions because quantitative biology requires in vitro culture
      systems that more authentically represent the cellular microenvironment in a
      living organism. In doing so, in vitro experimentation can become truly more
      predictive of in vivo systems.

PMID- 18037410
TI  - Dendritic cells in cancer immunotherapy.
AB  - Since their discovery, there has been significant progress in the understanding
      of dendritic cell (DC) biology. Their capacity for priming an immune response
      against pathogens and cancers has been exploited clinically. However, the
      objective responses obtained to date using DC cancer vaccines have been modest.
      Suboptimal DC preparations, limited tumor target antigens, and the essential need
      to initiate trials in immunocompromised patients with advanced disease, have all
      contributed to limited outcomes. The use of fully activated DCs, loaded with
      multiple, immunogenic, cancer-specific antigens, administered to patients with
      minimal residual disease and the manipulation of regulatory mechanisms underlying
      peripheral tolerance, may be the ingredients for future success.

PMID- 18037411
TI  - Distinct protein domains regulate ciliary targeting and function of C. elegans
      PKD-2.
AB  - TRPP2 (transient receptor potential polycystin-2) channels function in a range of
      cells where they are localized to specific subcellular regions including the
      endoplasmic reticulum (ER) and primary cilium. In humans, TRPP2/PC-2 mutations
      severely compromise kidney function and cause autosomal dominant polycystic
      kidney disease (ADPKD). The Caenorhabditis elegans TRPP2 homolog, PKD-2, is
      restricted to the somatodendritic (cell body and dendrite) and ciliary
      compartments of male specific sensory neurons. Within these neurons PKD-2
      function is required for sensation. To understand the mechanisms regulating TRPP2
      subcellular distribution and activity, we performed in vivo structure-function
      localization studies using C. elegans as a model system. Our data demonstrate
      that somatodendritic and ciliary targeting requires the transmembrane (TM) region
      of PKD-2 and that the PKD-2 cytosolic termini regulate subcellular distribution
      and function. Within neuronal cell bodies, PKD-2 colocalizes with the OSM-9 TRP
      vanilloid (TRPV) channel, suggesting that these TRPP and TRPV channels may
      function in a common process. When human TRPP2/PC-2 is heterologously expressed
      in transgenic C. elegans animals, PC-2 does not visibly localize to cilia but
      does partially rescue pkd-2 null mutant defects, suggesting that human PC-2 and
      PKD-2 are functional homologs.

PMID- 18037413
TI  - Guidelines on iron chelation therapy in patients with myelodysplastic syndromes
      and transfusional iron overload.
AB  - Experts believe that iron overload is an important problem which could be avoided
      with suitable treatment. Guidelines on treating myelodysplastic syndromes (MDS)
      include sections on using iron chelation therapy to prevent or ameliorate
      transfusional iron overload. The proportion of MDS patients who may benefit from
      iron chelation therapy is 35-55%, depending on the length of survival necessary
      for iron to accumulate to a detrimental level. Candidates for iron chelation are
      mainly patients with dyserythropoietic and cytopenic subtypes of disease, which
      fall into the International Prognostic Scoring System (IPSS) Low-risk or
      Intermediate-1-risk categories, with median survival of 3-6 years.

PMID- 18037414
TI  - Novel treatment options for transfusional iron overload in patients with
      myelodysplastic syndromes.
AB  - Red blood cell transfusion dependency is common in myelodysplastic syndromes and
      is associated with inferior survival. The use of parenteral deferoxamine therapy
      for transfusional iron overload has been sparse, in part due to cumbersome
      administration schedules. Deferasirox is an oral iron-chelating agent with
      favorable pharmacokinetics, including a long half-life allowing continuous 24
      hour chelation with once-daily dosing. Deferasirox produces dose-dependent
      reductions in liver iron content and reduces cardiac iron levels. In-vitro
      studies with deferasirox suggest improved cardiomyocyte contractility potentially
      important in reducing excess cardiac mortality noted in transfusion-dependent
      MDS. Deferasirox has a manageable safety profile with favorable patient
      satisfaction reports.

PMID- 18037415
TI  - Impact of transfusion dependency and secondary iron overload on the survival of
      patients with myelodysplastic syndromes.
AB  - Transfusion dependency is an independent prognostic factor in myelodysplastic
      syndromes (MDS). The detrimental effect on survival is related to the severity of
      transfusion requirement and is more noticeable in low-risk patients. Elevated
      serum ferritin levels have a poor prognostic impact on the survival of
      transfusion-dependent patients with refractory anemias, and can adversely affect
      the outcome of patients with MDS receiving allogeneic stem-cell transplantation.
      Sequential measurements of serum ferritin are useful for measuring secondary iron
      overload in MDS patients. The implementation of non-invasive methods for
      assessing tissue iron and organ function should clarify the impact of iron
      mediated organ damage on patients with MDS.

PMID- 18037416
TI  - Improving clinical outcome in patients with myelodysplastic syndrome and iron
      overload using iron chelation therapy.
AB  - Until recently, little information on the benefits of iron chelation therapy
      (ICT) in patients with myelodysplastic syndrome (MDS) and iron overload was
      known. A recent retrospective study showed improved survival in transfusion
      dependent patients with MDS (Low or Intermediate-1 risk IPSS) receiving ICT,
      compared with those not receiving ICT; median overall survival was not reached at
      160 months versus 40 months, respectively. Significantly more patients receiving
      ICT survived to 4 years (80% versus 44%; p < 0.03), suggesting that MDS patients
      with iron overload might benefit from ICT. Prospective studies to confirm the
      benefit of ICT in MDS are warranted.

PMID- 18037417
TI  - A flow sensitive alternating inversion recovery (FAIR)-MRI protocol to measure
      hemispheric cerebral blood flow in a mouse stroke model.
AB  - Blood flow imaging is an important tool in cerebrovascular research. Mice are of
      special interest because of the potential of genetic engineering. Magnetic
      resonance imaging (MRI) provides three-dimensional noninvasive quantitative
      methods of cerebral blood flow (CBF) imaging, but these MRI techniques have not
      yet been validated for mice. The authors compared CBF imaging using flow
      sensitive alternating inversion recovery (FAIR)-MRI and (14)C-Iodoantipyrine
      (IAP)-autoradiography in a mouse model of acute stroke. Twenty-nine male
      129S6/SvEv mice were subjected to filamentous left middle cerebral artery
      occlusion (MCAo). CBF imaging was performed with (14)C-IAP autoradiography and
      FAIR-MRI using two different anesthesia protocols, namely intravenous infusion of
      etomidate or inhalation of isoflurane, which differentially affect perfusion.
      Using (14)C-IAP autoradiography, the average CBF in ml/(100 g*min) was 160+/-34
      (isoflurane, n=5) vs. and 59+/-21 (etomidate, n=7) in the intact hemisphere and
      43+/-12 (isoflurane, n=5) vs. 36+/-12 (etomidate, n=7) in the MCAo hemisphere.
      Using FAIR-MRI, the corresponding average CBFs were 208+/-56 (isoflurane, intact
      hemisphere, n=7), 84+/-9 (etomidate, intact hemisphere, n=7), 72+/-22
      (isoflurane, MCAo hemisphere, n=7) and 48+/-13 (etomidate, MCAo hemisphere, n=7).
      Regression analysis showed a strong linear correlation between CBF measured with
      FAIR-MRI and (14)C-IAP autoradiography, and FAIR-MRI overestimated CBF compared
      to autoradiography. FAIR-MRI provides repetitive quantitative measurements of
      hemispheric CBF in a mouse model of stroke.

PMID- 18037418
TI  - Comparison of scarred and unscarred uterine ruptures.

PMID- 18037419
TI  - Characterization of the local immune response to cyst antigens during the acute
      and elimination phases of primary murine giardiasis.
AB  - During the course of a giardial infection, the host's immune system is presented
      with a variety of Giardia antigens as trophozoites differentiate, through
      encysting cells, to form the infective cysts. Previous studies examining the
      host's immune response during giardial infections have focused on trophozoite
      derived antigens (Ags). In this study, we were interested to determine if the
      host's immune system reacts to cyst Ags during the acute and elimination phases,
      when there is cyst shedding. For this purpose, we used antigenic extracts from
      trophozoites (Troph), encysting cells (ENC), and purified giardial cyst walls
      (PCW), as well as purified recombinant cyst wall protein 2 (rCWP2). Comparative
      analysis of the parasite extracts using SDS-PAGE analysis and surface-enhanced
      laser desorption/ionization time of flight mass spectrometry resulted in the
      detection of 175 protein entities, of which 26 were Troph-specific proteins, 17
      ENC-specific proteins, and 31 were PCW-specific proteins. On the other hand, we
      detected 34 proteins shared between Troph and ENC, 19 proteins that were shared
      between ENC and PCW, and 29 proteins that were common to Troph and PCW. Finally,
      we detected 19 proteins that were shared by all three extract samples. BALB/c
      mice were infected with 10(5)Giardia muris cysts and sacrificed either at the
      acute or elimination phases of infection (days 12 and 40, respectively), and
      lymphocytes were isolated from the Peyer's patches (PP). Using flow cytometry, we
      detected significant increases in the number of PP-derived CD4(+) and CD19(+),
      but not CD8(+) lymphocytes. Quantification of the number of mucosal IL-4 and IFN
      gamma secreting T-lymphocytes by enzyme-linked immunosorbent spot assay showed
      that these cells reacted by secreting similar levels of IL-4 and IFN-gamma,
      regardless of the Ag or the phase of infection. Analysis of intestinal humoral
      immune responses by ELISA resulted in the detection of Ag-specific IgA and IgG
      intestinal antibodies. Regardless of the Ag tested, a trend was consistently
      observed where the concentration of local antibodies was found to be slightly
      increased by the acute phase, where we detected approximately 200microg/mg of
      specific IgA and approximately 300ng/ml of specific IgG in intestinal lavage of
      infected mice. By the elimination phase, the amount of specific antibodies was
      found to increase to approximately 600microg/mg of specific IgA and approximately
      1300ng/ml of specific IgG antibodies. Finally, we tested the biological activity
      of these antibodies and found that they were able to reduce the ability of
      trophozoites to differentiate into cysts in vitro. Collectively, we believe these
      results demonstrate for the first time the existence of significant cellular and
      humoral immune responses against Giardia cyst Ags that may contribute to the
      reduction of cyst shedding in infected animals.

PMID- 18037420
TI  - Serum gamma-glutamyltransferase level and peripheral arterial disease.
AB  - OBJECTIVE: We examined the association between increasing serum GGT levels and
      PAD in the US general population. METHODS: Cross-sectional study among 3941
      National Health and Nutrition Examination Survey 1999-2002 participants aged
      >or=40 years. Main outcome-of-interest was PAD defined as ankle-brachial index
      <0.9 (n=219). RESULTS: Overall, serum GGT levels were positively associated with
      PAD among men but not women (p-interaction=0.0421). Among men, the multivariable
      odds ratio (OR) [95% confidence intervals (CI)] comparing the highest quartile of
      serum GGT (>35U/L) to the lowest quartile (<16U/L) was 4.25 (1.65-10.94); p
      trend=0.0008. Also the observed positive association between GGT quartiles and
      PAD among men was predominantly present among non-Hispanic whites and current
      nondrinkers (multivariable OR [95% CI] comparing the highest quartile of serum
      GGT to the lowest quartile was 10.59 [2.31-48.55]; p-trend=0.0104). In contrast
      among women, the multivariable OR (95% CI) comparing the highest quartile of
      serum GGT to the lowest quartile was 0.76 (0.41-1.41); p-trend=0.8308.
      CONCLUSIONS: There was a positive association between serum GGT level and PAD
      among men, particularly non-Hispanic white and nondrinker men, but not among
      women. Future prospective studies are required to clarify the temporal nature of
      this relationship and to confirm the observed gender-specific nature of this
      association.

PMID- 18037421
TI  - Rapid identification of fatty acid methyl esters using a multidimensional gas
      chromatography-mass spectrometry database.
AB  - A multidimensional approach for the identification of fatty acid methyl esters
      (FAME) based on GC/MS analysis is described. Mass spectra and retention data of
      more than 130 FAME from various sources (chain lengths in the range from 4 to 24
      carbon atoms) were collected in a database. Hints for the interpretation of FAME
      mass spectra are given and relevant diagnostic marker ions are deduced indicating
      specific groups of fatty acids. To verify the identity of single species and to
      ensure an optimized chromatographic resolution, the database was compiled with
      retention data libraries acquired on columns of different polarity (HP-5, DB-23,
      and HP-88). For a combined use of mass spectra and retention data standardized
      methods of measurement for each of these columns are required. Such master
      methods were developed and always applied under the conditions of retention time
      locking (RTL) which allowed an excellent reproducibility and comparability of
      absolute retention times. Moreover, as a relative retention index system,
      equivalent chain lengths (ECL) of FAME were determined by linear interpolation.
      To compare and to predict ECL values by means of structural features, fractional
      chain lengths (FCL) were calculated and fitted as well. As shown in an example,
      the use of retention data and mass spectral information together in a database
      search leads to an improved and reliable identification of FAME (including
      positional and geometrical isomers) without further derivatizations.

PMID- 18037422
TI  - Novel method to prepare polystyrene-based monolithic columns for chromatographic
      and electrophoretic separations by microwave irradiation.
AB  - Microwave irradiation can provide a viable alternative to the traditional means
      such as ultraviolet light and thermal initiation for the preparation of
      monolithic capillary columns. Polystyrene-based monolithic stationary phases were
      prepared in situ in fused-silica capillaries and simultaneously in vials. The
      column permeability, electrophoretic and chromatographic behavior were evaluated
      using pressure-assisted capillary electrochromatography (pCEC), capillary
      electrochromatography (CEC) and low pressure liquid chromatography (LPLC). With
      an optimal monolithic material, the largest theoretical plates for preparing the
      column could be close to 18,000 plates/m for thiourea in the mode of pCEC.
      Furthermore, the influence of the composition of the porogenic solvents
      (toluene/isooctane) on the morphology of organic-based monoliths [poly(styrene
      divinylbenzene-methacrylic acid)] was systematically studied with mercury
      intrusion porosimetry and scanning electron microscopy. The monoliths which were
      prepared with a high content of isooctane had a bigger pore size and better
      permeability, and hence resulted in a faster separation.

PMID- 18037423
TI  - Investigation of salt properties with electro-acoustic measurements and their
      effect on dynamic binding capacity in hydrophobic interaction chromatography.
AB  - The pH dependence in hydrophobic interaction chromatography (HIC) is usually
      discussed exclusively in terms of protein dependence and there are no clear
      defined trends. Many of the deviations from an ideal solution are caused solely
      by the high salt concentration, as protein concentration is usually negligible.
      So pH dependency in hydrophobic interaction chromatography could also be the
      result of pH dependent changes of ion properties from the salt solution. The
      possibility that pH dependent ion hydration or ion association in highly
      concentrated salt solutions may influence the dynamic protein binding capacity
      onto HIC resins was investigated. In buffer solutions commonly used in HIC e.g.
      sodium chloride, ammonium sulphate and sodium citrate pH dependent maxima in the
      electro-acoustic signals were found. These maxima are related to an increase of
      the ion sizes by hydration or ion association. At low ionic strength the maxima
      are in the range between 4.5 and 6 and they increased in concentrated electrolyte
      solutions to values between 6 and 8. The range of these maxima is in the same
      region as dynamic protein binding capacity maxima often observed in HIC. For a
      qualitative interpretation of this phenomenon of increased protein stabilization
      by volume exclusion effect extended scaling theory can be used. This theory
      predicts a maximum of protein stabilization if the ratio of salt ion diameter to
      water is 1.8. According to the hypothesis raised here, if the pH dependent ratio
      of salt ion diameter to water approaches this value the transport of the protein
      in the pore system is less restricted and an increase in binding capacity can be
      produced.

PMID- 18037424
TI  - Isolation of three sesquiterpene lactones from the roots of Cichorium glandulosum
      Boiss. et Huet. by high-speed counter-current chromatography.
AB  - Because of the skeletal complexity and similarity of the polarity, little
      research was reported on the isolation of sesquiterpene lactones by high-speed
      counter-current chromatography (HSCCC). Herein, three sesquiterpene lactones were
      successfully purified from the ethyl acetate extract of the roots of the
      traditional Uyghur medicinal plant Cichorium glandulosum Boiss. et Huet. by
      HSCCC. The separation was performed in two steps with two solvent systems: n
      hexane-ethyl acetate-methanol-water (1.5:5:2.75:5, v/v/v/v) and ethyl acetate
      methanol-water (20:1:20, v/v/v). From 166 mg of the ethyl acetate extract, 19 mg
      of lactucopicrin was isolated with the first solvent system and 10 mg of
      11beta,13-dihydrolactucin and 16 mg of lactucin were obtained with the second
      solvent system. All purified compounds were over 94% purity as determined by HPLC
      analysis, and these chemical structures were confirmed by (1)H NMR and (13)C NMR.

PMID- 18037425
TI  - Preparation of two new liquid chromatographic chiral stationary phases based on
      diastereomeric chiral crown ethers incorporating two different chiral units and
      their applications.
AB  - Two new liquid chromatographic chiral stationary phases based on diastereomeric
      chiral crown ethers incorporating two different chiral units such as optically
      active 3,3'-diphenyl-1,1'-binaphthyl and tartaric acid unit were prepared.
      Between the two CSPs, one was much superior to the other especially in the
      resolution of tocainide and its analogues (for example, in the resolution of
      tocainide the separation factor, alpha, was 4.26 vs. 1.00 on the two CSPs). From
      these results, the two chiral units composing the two diastereomeric chiral crown
      ether moieties of the stationary phases were expected to show "matched" or
      "mismatched" effect on the chiral recognition according to their stereochemistry.
      The different chiral recognition abilities of the two CSPs were rationalized by
      the different three-dimensional structures of the two diastereomeric chiral crown
      ethers.

PMID- 18037426
TI  - Comparative study on the separation behavior of monolithic columns prepared via
      ring-opening metathesis polymerization and via electron beam irradiation
      triggered free radical polymerization for proteins.
AB  - Monolithic columns have been prepared via ring-opening metathesis polymerization
      using different monomers and crosslinkers, i.e. norborn-2-ene, 1,4,4a,5,8,8a
      hexahydro-1,4,5,8-exo,endo-dimethanonaphthalene, cyclooctene and tris(cyclooct-4
      en-1-yloxy)methylsilane. 2-Propanol and toluene were used as macro- and
      microporogens. Alternatively, monolithic supports were realized via electron beam
      triggered free radical polymerization using trimethylolpropane triacrylate and
      ethylmethacrylate. Here, 2-propanol, 1-dodecanol and toluene were used as
      porogens. The three monolithic supports were structurally characterized by
      inverse size exclusion chromatography and investigated for their separation
      capabilities for a series of proteins. Separation efficiencies are discussed
      within the context of the different structural features of the monolithic
      supports and are compared to the separation data obtained on a commercial silica
      based Chromolith RP-18e column.

PMID- 18037427
TI  - Use of 120-nm deep channels for liquid chromatographic separations.
AB  - The present study reports on the exploration of the separation speed limits of
      RPLC chromatography in open-tubular channels. Applying the shear-driven
      chromatography principle in a 120-nm deep open channel, and using an improved
      detection set-up, the separation of three coumarin dyes was detectable 8mm
      downstream of the injection point. At this distance, separation efficiencies of N
      = 17,900 - 24,100 plates were obtained at a velocity of 10 mm s(-1),
      corresponding to a plate generation velocity of 21,100 to 28,300 plates per
      second for the most and least retained component, respectively.

PMID- 18037428
TI  - Prediction of the influence of the heat generated by viscous friction on the
      efficiency of chromatography columns.
AB  - The combination of the heat balance in a chromatographic column percolated by a
      stream of mobile phase and of the model of band migration under linear conditions
      along such a column permits the calculation of the axial and radial temperature
      distributions in the column, of the elution band profiles, and of the column
      efficiency under different sets of experimental conditions. The calculated
      results are always consistent with the experimental results published by
      different groups and often in good quantitative agreement. Minor discrepancies
      arise from difficulties in deriving precise estimates of the heat transfers from
      the column due to the massive endfittings of the column and to uncontrolled heat
      transfer from the column tube to ambient air.

PMID- 18037429
TI  - Solid-phase microextraction-gas chromatographic-tandem mass spectrometric
      analysis of polycyclic aromatic hydrocarbons. Towards the European Union water
      directive 2006/0129 EC.
AB  - This article presents a solid-phase microextraction (SPME) procedure to determine
      27 parent and alkylated polycyclic aromatic hydrocarbons (PAHs) with diverging
      polarities and molecular masses in various types of water samples (tap, well,
      superficial, and seawater). A 65-microm polydimethylsiloxane-divinylbenzene
      (PDMS/DVB) fiber was used, and parameters affecting the extraction procedures
      such as extraction temperature and time, desorption temperature and time,
      splitless time, effect of an organic modifier or ionic adjustment were studied.
      The linearity and precision of the proposed method were satisfactory. The use of
      GC-MS determination in the full scan mode, in the selected ion monitoring (SIM)
      mode, and in the GC-MS-MS mode provided the unequivocal identification and
      quantification of the target analytes. Moreover, the proposed SPME-GC-MS-MS
      method, extracting only 18 ml of sample, reached the very restrictive limits
      fixed by the 2006/0129 EC proposal for a new water directive to be achieved by
      2015. The matrix effects were evaluated through the analysis of tap, well,
      superficial, and seawater. A discussion on different behaviors, a result of the
      matrix effects, was included. Analytical recoveries were satisfactory in all
      cases. The novelty of this work consisted in the wide range of analyzed PAHs, the
      very low detection limits that were reached, the coupling of SPME-GC-MS-MS, and
      the study of the matrix effect on water samples. With this developed procedure,
      detection limits between 0.07 and 0.76 ng l(-1) and quantification limits between
      0.10 and 0.98 ng l(-1) were obtained with MS-MS detection. Moreover, the
      analytical recoveries for different aqueous matrices were near 100% in all cases.

PMID- 18037430
TI  - Poly(phthalazine ether sulfone ketone) as novel stationary phase for stir bar
      sorptive extraction of organochlorine compounds and organophosphorus pesticides.
AB  - A novel poly(phthalazine ether sulfone ketone) (PPESK) film prepared by immersion
      precipitation technique was coated on stir bars for sorptive extraction. Scanning
      electron micrographs showed that the coating has a denser porous surface (about 1
      microm in thickness) with a sponge-like sublayer, and the thickness of the
      coating was 250 microm. The PPESK coated stir bar has high thermostability (290
      degrees C) and long lifetime (50 times). The extraction properties of this stir
      bar were evaluated for the extraction of both polar and semi-polar analytes,
      including organochlorine compounds and organophosphorus pesticides. The PPESK
      stir bar was proved to show higher affinity towards polar compounds than that of
      PDMS coated stir bar and higher sample load compared with corresponding PPESK
      fiber. It was applied to the determination of organochlorine compounds in
      seawater samples and organophosphorus pesticides in juices by gas chromatographic
      analysis. The effect of sample matrix was evaluated at optimized condition of
      extraction temperature, extraction time and salt concentration. Limits of
      detection were in the range of 0.05-2.53 ng L(-1) for organochlorine compounds in
      seawater samples using electron capture detector (ECD), with precisions of less
      than 11% RSD. Limits of detection for organophosphorus pesticides were in the
      range of 0.17-2.25 ng L(-1) and 2.47-10.3 ng L(-1) in grape and peach juice,
      respectively, using thermionic specified detector (TSD), with precisions of less
      than 12% RSD and 20% RSD, respectively.

PMID- 18037431
TI  - Isotope dilution for quantitation of steroid estrogens and nonylphenols by gas
      chromatography with tandem mass spectrometry in septic, soil, and groundwater
      matrices.
AB  - A simplified, in-line solid-phase extraction and clean-up process is presented
      for rapid extraction and analysis of steroid estrogens and nonylphenols by gas
      chromatography with tandem mass spectrometry. Isotope dilution with multiple
      deuterated standards has been developed, evaluated, and verified using this
      method against standard addition for the analysis of estrone, estradiol, estriol,
      ethinylestradiol, and 4-nonylphenols in septic, soil, and groundwater matrices.
      The accuracy and precision of isotope dilution was comparable to standard
      addition yet was able to quantify analytes with the use of fewer samples by
      including [(2)H(4)]estradiol, [(2)H(4)]ethinylestradiol, [(2)H(4)]nonylphenol,
      and estradiol-17-acetate as internal standards. Specific details and validation
      of the method are presented as are data showing the occurrence of estrogens and
      nonylphenols in an on-site wastewater treatment (septic) system with advanced
      stages of pretreatment and recirculation to an office building for non-potable
      reuse.

PMID- 18037432
TI  - [Survey of mishaps related to the use of cardiopulmonary bypass: time for
      creation of a French national center?].

PMID- 18037433
TI  - Differential expression of cardiac neurotrophic factors and sympathetic nerve
      ending abnormalities within the failing heart.
AB  - In congestive heart failure (CHF), cardiac sympathetic nerve endings
      transdifferentiate from a balanced norepinephrine (NE) storage/release/uptake
      apparatus to a nerve that predominantly releases NE. Little is known about the
      neurotrophic factors that may trigger this process. In the present study, we
      evaluated the cardiac expression pattern of nerve growth factor (NGF),
      neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and ciliary
      neurotrophic factor (CNTF) in salt-sensitive Dahl rats (DS), which are
      characterized by profound alterations of the cardiac sympathetic nervous system.
      Experiments were performed in male DS and salt-resistant Dahl rats (DR) 30, 40
      and 50 days after onset of high-salt intake. The sympathetic nerve density was
      measured by glyoxylic acid-induced histofluorescence. Cardiac NE re-uptake was
      assessed by isolated heart perfusion with [(3)H]-NE and norepinephrine
      transporter (NET) mRNA by real-time PCR. Cardiac expression of neurotrophic
      factors was determined by ribonuclease protection assay and Western blot
      analysis. DS rats displayed reduced left ventricular sympathetic nerve endings 40
      days after onset of high-salt intake, which was preceded by an impaired cardiac
      [(3)H]-NE uptake. NGF, a positive regulator of NE re-uptake, and NT-3 were down
      regulated already 30 days after onset of high-salt intake, whereas BDNF and CNTF
      protein expression were increased not before 40 days after onset of high-salt
      intake. In conclusion, during the development of CHF, a dysregulated NE
      storage/release/uptake apparatus within the sympathetic nerve endings might be
      triggered by differential expression of cardiac neurotrophic factors.

PMID- 18037435
TI  - A competition mechanism regulates the translation of the Escherichia coli operon
      encoding ribosomal proteins L35 and L20.
AB  - Escherichia coli ribosomal protein (r-protein) L20 is essential for the assembly
      of the 50S ribosomal subunit and is also a translational regulator of its own
      rpmI-rplT operon, encoding r-proteins L35 and L20 in that order. L20 directly
      represses the translation of the first cistron and, through translational
      coupling, that of its own gene. The translational operator of the operon is 450
      nt in length and includes a long-range pseudoknot interaction between two RNA
      sequences separated by 280 nt. L20 has the potential to bind both to this
      pseudoknot and to an irregular hairpin, although only one site is occupied at a
      time during regulation. This work shows that the rpmI-rplT operon is regulated by
      competition between L20 and the ribosome for binding to mRNA in vitro and in
      vivo. Detailed studies on the regulatory mechanisms of r-protein synthesis have
      only been performed on the rpsO gene, regulated by r-protein S15, and on the
      alpha operon, regulated by S4. Both are thought to be controlled by a trapping
      mechanism, whereby the 30S ribosomal subunit, the mRNA, and the initiator tRNA
      are blocked as a nonfunctional preternary complex. This alternative mode of
      regulation of the rpmI-rplT operon raises the possibility that control is
      kinetically and not thermodynamically limited in this case. We show that the
      pseudoknot, which is known to be essential for L20 binding and regulation, also
      enhances 30S binding to mRNA as if this structure is specifically recognised by
      the ribosome.

PMID- 18037434
TI  - Prevention of cardiac hypertrophy and heart failure by silencing of NF-kappaB.
AB  - Activation of the nuclear factor (NF)-kappaB signaling pathway may be associated
      with the development of cardiac hypertrophy and its transition to heart failure
      (HF). The transgenic Myo-Tg mouse develops hypertrophy and HF as a result of
      overexpression of myotrophin in the heart associated with an elevated level of NF
      kappaB activity. Using this mouse model and an NF-kappaB-targeted gene array, we
      first determined the components of NF-kappaB signaling cascade and the NF-kappaB
      linked genes that are expressed during the progression to cardiac hypertrophy and
      HF. Second, we explored the effects of inhibition of NF-kappaB signaling events
      by using a gene knockdown approach: RNA interference through delivery of a short
      hairpin RNA against NF-kappaB p65 using a lentiviral vector (L-sh-p65). When the
      short hairpin RNA was delivered directly into the hearts of 10-week-old Myo-Tg
      mice, there was a significant regression of cardiac hypertrophy, associated with
      a significant reduction in NF-kappaB activation and atrial natriuretic factor
      expression. Our data suggest, for the first time, that inhibition of NF-kappaB
      using direct gene delivery of sh-p65 RNA results in regression of cardiac
      hypertrophy. These data validate NF-kappaB as a therapeutic target to prevent
      hypertrophy/HF.

PMID- 18037436
TI  - Spectral characteristics of the photocycle of channelrhodopsin-2 and its
      implication for channel function.
AB  - In 2003, channelrhodopsin-2 (ChR2) from Chlamydomonas reinhardtii was discovered
      to be a light-gated cation channel, and since that time the channel became an
      excellent tool to control by light neuronal cells in culture as well as in living
      animals with high temporal and spatial resolution in a noninvasive manner.
      However, little is known about the spectral properties and their relation to the
      channel function. We have expressed ChR2 in the yeast Pichia pastoris and
      purified the protein. Flash-photolysis data were combined with patch-clamp
      studies to elucidate the photocycle. The protein absorbs maximally at
      approximately 480 nm before light excitation and shows flash-induced absorbance
      changes with at least two different photointermediates. Four relaxation processes
      can be extracted from the time course that we have analysed in a linear model for
      the photocycle leading to the kinetic intermediates P(1) to P(4). A short-lived
      photointermediate at 400 nm, suggesting a deprotonation of the retinal Schiff
      base, is followed by a red-shifted (520 nm) species with a millisecond lifetime.
      The first three kinetic intermediates in the photocycle, P(1) to P(3), are
      described mainly by the red-shifted 520-nm species. The 400-nm species
      contributes to a smaller extent to P(1) and P(2). The fourth one, P(4), is
      spectroscopically almost identical with the ground state and lasts into the
      seconds time region. We compared the spectroscopic data to current measurements
      under whole-cell patch-clamp conditions on HEK 293 cells. The lifetimes of the
      spectroscopically and electrophysiologically determined intermediates are in
      excellent agreement. The intermediates P(2) and P(3) (absorbing at 520 nm) are
      identified as the cation permeating states of the channel. Under stationary
      light, a modulation of the photocurrent by green light (540 nm) was observed. We
      conclude that the red-shifted spectral species represents the open channel state,
      and the thermal relaxation of this intermediate, the transition from P(3) to
      P(4), is coupled to channel closing.

PMID- 18037439
TI  - "Our most vulnerable clients...".

PMID- 18037437
TI  - Actin hydrophobic loop 262-274 and filament nucleation and elongation.
AB  - The importance of actin hydrophobic loop 262-274 dynamics to actin polymerization
      and filament stability has been shown recently with the use of the yeast mutant
      actin L180C/L269C/C374A, in which the hydrophobic loop could be locked in a
      "parked" conformation by a disulfide bond between C180 and C269. Such a cross
      linked globular actin monomer does not form filaments, suggesting nucleation
      and/or elongation inhibition. To determine the role of loop dynamics in filament
      nucleation and/or elongation, we studied the polymerization of the cross-linked
      actin in the presence of cofilin, to assist with actin nucleation, and with
      phalloidin, to stabilize the elongating filament segments. We demonstrate here
      that together, but not individually, phalloidin and cofilin co-rescue the
      polymerization of cross-linked actin. The polymerization was also rescued by
      filament seeds added together with phalloidin but not with cofilin. Thus, loop
      immobilization via cross-linking inhibits both filament nucleation and
      elongation. Nevertheless, the conformational changes needed to catalyze ATP
      hydrolysis by actin occur in the cross-linked actin. When actin filaments are
      fully decorated by cofilin, the helical twist of filamentous actin (F-actin)
      changes by approximately 5 degrees per subunit. Electron microscopic analysis of
      filaments rescued by cofilin and phalloidin revealed a dense contact between
      opposite strands in F-actin and a change of twist by approximately 1 degrees per
      subunit, indicating either partial or disordered attachment of cofilin to F-actin
      and/or competition between cofilin and phalloidin to alter F-actin symmetry. Our
      findings show an importance of the hydrophobic loop conformational dynamics in
      both actin nucleation and elongation and reveal that the inhibition of these two
      steps in the cross-linked actin can be relieved by appropriate factors.

PMID- 18037438
TI  - Restriction endonuclease inhibitor IPI* of bacteriophage T4: a novel structure
      for a dedicated target.
AB  - Phage T4 protects its DNA from the two-gene-encoded gmrS/gmrD (glucose-modified
      hydroxymethylcytosine restriction endonuclease) CT of pathogenic Escherichia
      coli, CT596, by injecting several hundred copies of the 76-amino-acid-residue
      nuclease inhibitor, IPI*, into the infected host. Here, the three-dimensional
      solution structure of mature IPI* is reported as determined by nuclear magnetic
      resonance techniques using 1290 experimental nuclear Overhauser effect and
      dipolar coupling constraints ( approximately 17 constraints per residue). Close
      examination of this oblate-shaped protein structure reveals a novel fold
      consisting of two small beta-sheets (beta1: B1 and B2; beta2: B3-B5) flanked at
      the N- and C-termini by alpha-helices (H1 and H2). Such a fold is very compact in
      shape and allows ejection of IPI* through the narrow 30-A portal and tail tube
      apertures of the virion without unfolding. Structural and dynamic measurements
      identify an exposed hydrophobic knob that is a putative gmrS/gmrD-binding site. A
      single gene from the uropathogenic E. coli UT189, which codes for a gmrS/gmrD
      like UT fusion enzyme (with approximately 90% identity to the heterodimeric CT
      enzyme), has evolved IPI* inhibitor immunity. Analysis of the gmrS/gmrD
      restriction endonuclease enzyme family and its IPI* family phage antagonists
      reveals an evolutionary pathway that has elaborated a surprisingly diverse and
      specifically fitted set of coevolving attack and defense structures.

PMID- 18037440
TI  - Transitional care for seriously mentally ill persons: a pilot study.
AB  - This article reports the results of a pilot study of a nurse-based in-home
      transitional care intervention for seriously mentally ill persons. The goals of
      the intervention were to address the lack of continuity of care in existing
      programs and to meet the immediate postdischarge needs of severely mentally ill
      persons. This article focuses primarily on the applicability and feasibility of
      the intervention for this population, given the challenges of engaging seriously
      mentally ill patients in a community-based protocol and the complexity of their
      illnesses. Factors that are important to community adjustment postdischarge were
      identified: caregiver concerns and health status impeding illness management,
      lack of structure/involvement in daily activities, structural and functional
      factors affecting adherence, and presence of symptoms after discharge. Use of an
      advanced practice nurse to provide transitional care can offer an alternative to
      patients who might otherwise be left poorly treated or untreated in the community
      setting.

PMID- 18037441
TI  - Psychometric properties of the 7-Day Physical Activity Recall questionnaire in
      individuals with severe mental illness.
AB  - Few self-report measures of physical activity have been validated in individuals
      with severe mental illness. The purpose of this study was to examine the validity
      and reliability of a 7-day recall measure (7DR: [Blair, S. N. (1984). How to
      assess exercise habits and physical fitness. In J. D. Matarazzo, N. E. Miller, &
      S. M. Weiss, (Eds.), Behavioural health: A handbook of health enhancement and
      disease prevention (pp. 424-447). New York: Wiley.]) through comparison with RT3
      triaxial accelerometry data. Fourteen individuals took part in the study.
      Validity was considered by Kendall's tau correlation and (Bland, J. M., & Altman,
      D. G. (1986). Statistical-methods for assessing agreement between 2 methods of
      clinical measurement. Lancet, 1(8476), 307-310) limits of agreement and test
      retest reliability was measured by ICC. The only significant correlation between
      measures was total energy expenditure (tau = 0.43). The 7-DR over reported
      moderate physical activity by 16.9 +/- 52.3 min/day, but under reported vigorous
      physical activity by -10.4 +/- 24.3 min/day. Test retest ICC was significant for
      all outcome measures. Overall, the 7-DR was reliable but exhibited questionable
      validity. The use of self-report questionnaires such as the 7-DR may inaccurately
      estimate the levels of physical activity in this population, and may not be
      sensitive to monitoring intervention-related changes in physical activity.

PMID- 18037442
TI  - Social skills training as nursing intervention to improve the social skills and
      self-esteem of inpatients with chronic schizophrenia.
AB  - The effects of social skills training on the social skills and self-esteem of 66
      patients with chronic schizophrenia were evaluated using the basic training and
      problem-solving training models. The experimental group received 16 group
      training sessions, and the control group received routine nursing care. The
      training program consisted of two parts: conversational skills and assertiveness
      skills. Data were collected at pretreatment and posttreatment. The
      conversational, interpersonal relationship, and assertiveness skills, and self
      esteem of the experimental group showed significant improvement, whereas problem
      solving skills did not improve. The results indicate that training in social
      skills is effective for improving the social skills and self-esteem of inpatients
      with chronic schizophrenia.

PMID- 18037443
TI  - The role of treatment setting and high acuity in the overdiagnosis of
      schizophrenia in African Americans.
AB  - Multiple studies have shown that significant disparities exist in the diagnosis
      of schizophrenia between African Americans (AAs) and Whites with severe mental
      illness. This phenomenon has been a topic in the literature for nearly three
      decades, yet it remains unclear what factors contribute most conclusively to the
      overdiagnosis of schizophrenia in AAs. The purpose of this article was to
      collectively examine the contributing factors identified in the literature and to
      discuss the role of acuity and treatment setting in overdiagnosis as well. A
      variety of client-level (higher rates of use of psychotomimetic substances in
      AAs) and care process-level (misinterpretation of cultural mistrust as paranoia,
      under detection of depression, similarities in diagnostic criteria between mood
      and psychotic disorders, provider bias, miscommunication between patient and
      provider, changes in diagnostic criteria, differences in diagnostic practice
      between providers, and a lack of sufficient data obtained) factors emerged as
      influential in overdiagnosis. However, in this review, it also emerged that AAs
      tendency to use emergency and acute care services, a systems level factor, could
      be related as well. It is possible that assessment at a time when symptom acuity
      is severe might increase the likelihood of a schizophrenia diagnosis in AAs.

PMID- 18037444
TI  - Transition to Community: a program to help clients with schizophrenia move from
      inpatient to community care; a pilot study.
AB  - A pilot study of the Transition to Community program tested the feasibility of
      conducting a larger trial using the same intervention. An advanced practice
      psychiatric nurse interviewed hospitalized clients, contacted outpatient
      clinicians, and communicated with clients after discharge via prepaid cellular
      phones. Client compliance with medications and outpatient appointments, and the
      number of hospital readmission days during the 50-day period after discharge were
      examined. The sample size (N = 13) precluded statistically significant data;
      however, collective results indicated a probable difference on at least one of
      the variables. Modifications in methods for a multisite trial, based on this
      pilot project, are identified in the summary.

PMID- 18037445
TI  - A neomodernist perspective for researching chronicity.

PMID- 18037447
TI  - From individual to collective displacements in heterogeneous environments.
AB  - Animal displacement plays a central role in many ecological questions. It can be
      interpreted as a combination of components that only depend on the animal (for
      example a random walk) and external influences given by the heterogeneity of the
      environment. Here we treat the case where animals switch between random walks in
      a homogeneous 2D environment and its 1D boundary, combined with a tendency for
      wall-following behaviour (thigmotactism) that is treated as a Markovian process.
      In the first part we use mesoscopic techniques to derive from these assumptions a
      set of partial differential equations (PDE) with specific boundary conditions and
      parameters that are directly given by the individual displacement parameters. All
      assumptions and approximations made during this derivation are rigorously
      validated for the case of exploratory behaviour of the ant Messor sanctus. These
      PDE predict that the stationary density ratio between the 2D (centre) and 1D
      (border) environment only depends on the thigmotactic component, not on the size
      of the centre or border areas. In the second part we test this prediction with
      the same exploratory behaviour of M. sanctus, in particular when many ants move
      around simultaneously and may interact directly or indirectly. The prediction
      holds when there is a low degree of heterogeneity (simple square arena with
      straight borders), the collective behaviour is "simply" the sum of the individual
      behaviours. But this prediction breaks down when heterogeneity increases
      (obstacles inside the arena) due to the emergence of pheromone trails. Our
      approach may be applied to study the effects of animal displacement in any
      environment where the animals are confronted with an alternation of 2D space and
      1D borders as for example in fragmented landscapes.

PMID- 18037448
TI  - Effects of an anti-oxidative ACAT inhibitor on apoptosis/necrosis and cholesterol
      accumulation under oxidative stress in THP-1 cell-derived foam cells.
AB  - THP-1 cell-derived foam cells were exposed to oxidative stress through combined
      treatment with acetylated LDL (acLDL) and copper ions (Cu2+). The foam cells
      showed caspase-dependent apoptotic changes on exposure to oxidative stress for 6
      h, and necrotic changes with the leakage of LDH after 24 h. KY-455, an anti
      oxidative ACAT inhibitor, and ascorbic acid (VC) but not YM-750, an ACAT
      inhibitor, prevented apoptotic and necrotic changes. These preventive effects of
      KY-455 and VC were accompanied by the inhibition of lipid peroxidation in culture
      medium containing acLDL and Cu2+, suggesting the involvement of oxidized acLDL in
      apoptosis and necrosis. Foam cells accumulated esterified cholesterol (EC) for 24
      h in the presence of acLDL without Cu2+, which was suppressed by KY-455 and YM
      750. Foam cells showed necrotic changes and died in the presence of acLDL and
      Cu2+. KY-455 but not YM-750 prevented cell death and reduced the amount of EC
      accumulated. The foam cells treated with VC further accumulated EC without
      necrotic changes for 24 h even in the presence of acLDL and Cu2+. YM-750 as well
      as KY-455 inhibited lipid accumulation when co-incubated with VC in foam cells
      exposed to oxidative stress. It is concluded that an anti-oxidative ACAT
      inhibitor or the combination of an antioxidant and an ACAT inhibitor protects
      foam cells from oxidative stress and effectively reduces cholesterol levels,
      which would be a promising approach in anti-atherosclerotic therapy.

PMID- 18037449
TI  - Activity and expression of ecto-5'-nucleotidase/CD73 are increased during
      phenotype conversion of a hepatic stellate cell line.
AB  - Hepatic stellate cells (HSC) play a crucial role in the development of liver
      fibrosis and are important targets in liver disease therapy. Adenosine acts as an
      extracellular signaling molecule in various tissues and in liver this nucleoside
      exerts protective effects. Ecto-5'-nucleotidase/CD73 is a marker for the plasma
      membrane and is considered to be a key enzyme in the generation of adenosine in
      the extracellular medium, by transforming AMP into adenosine. In addition,
      adenosine production from AMP is also catalyzed by alkaline phosphatase. We
      compared the extracellular metabolism of AMP and transcriptional levels of the
      ecto-5'-nucleotidase/CD73 and tissue non-specific alkaline phosphatase (TNALP) in
      activated and quiescent HSC of the mouse hepatic stellate cell line GRX. This
      cell line expresses a myofibroblast phenotype in basal medium and both retinol
      and indomethacin treatment induced a phenotypic change of GRX cells to quiescent
      HSC. Ecto-5'-nucleotidase activity and its mRNA expression were found to be
      higher in quiescent HSC than in activated HSC. During phenotype conversion,
      mediated by retinol, the AMP decay was accelerated with adenosine accumulation in
      extracellular medium, likely due to the decrease in adenosine deaminase activity
      also observed in quiescent HSC. The treatment with retinol also involves
      transcriptional activation of TNALP. Taken together, these data suggest that ecto
      5'-nucleotidase-dependent adenosine generation may play a role in the regulation
      of quiescent HSC functions.

PMID- 18037450
TI  - Co-inoculation of Capitella sp. I with its synergistic bacteria enhances
      degradation of organic matter in organically enriched sediment below fish farms.
AB  - A polychaete, Capitella sp. I has been shown to degrade organics actively in
      organically enriched sediment below fish farms. Our aim of the present study is
      to enhance the biological treatment of sediment by co-inoculation of Capitella
      sp. I with bacterial isolates that possess high degrading potential for organic
      matter. We isolated a total of 200 bacterial strains from fecal pellets, burrow
      lining, worm body, and sediment, and selected six of them for the degradation
      experiments in the sediment microcosms. With two out of the six isolates,
      tentatively identified as Vibrio sp. and Vibrio cyclitrophicus by 16SrDNA
      sequence, we found the TOC reduction rate was stimulated in sediment co
      inoculated with the worms and each of the bacteria. In contrast, this was not
      observed in sediments inoculated only with the worms or the bacterium. These
      results strongly suggest that co-inoculation of Capitella sp. I with bacteria
      improves biodegradation.

PMID- 18037451
TI  - The novel compound (+/-)-1-[10-((E)-3-Phenyl-allyl)-3,10-diaza-bicyclo[4.3.1]dec
      3-yl]-propan-1-one (NS7051) attenuates nociceptive transmission in animal models
      of experimental pain; a pharmacological comparison with the combined mu-opioid
      receptor agonist and monoamine reuptake inhibitor tramadol.
AB  - Tramadol is an atypical analgesic with a unique dual mechanism of action. It acts
      on monoamine transporters to inhibit reuptake of noradrenaline (NA) and serotonin
      (5-HT), and consequent upon metabolism, displays potent agonist activity at micro
      opioid receptors. Here, we present data for the novel compound NS7051, which was
      shown to have sub-micromolar affinity (Ki=0.034microM) for micro-opioid receptors
      and inhibited reuptake of 5-HT, NA and DA (IC(50)=4.2, 3.3 and 3.5microM in
      cortex, hippocampus and striatum respectively). NS7051 (1-30mg/kg, s.c.) produced
      a dose-dependent naloxone-reversible increase in the hot plate withdrawal
      latency, and was also analgesic in the tail flick test. In models of persistent
      and chronic inflammatory nociception, NS7051 reversed flinching behaviours during
      interphase and second phase of the formalin test (ED(50)=1.7 and 1.8mg/kg, s.c.),
      and hindpaw weight-bearing deficits induced by complete Freund's adjuvant
      injection (ED50=1.2mg/kg, s.c.). In the chronic constriction injury model of
      neuropathic pain, mechanical allodynia and hyperalgesia were both reversed by
      NS7051 (ED50=6.7 and 4.9mg/kg, s.c.). Tramadol was also active in all pain models
      although at considerably higher doses (20-160mg/kg, s.c.). No ataxia was observed
      at antiallodynic doses giving therapeutic indices of 19 and 3 for NS7051 and
      tramadol. The combined opioid receptor agonism and monoamine reuptake inhibitory
      properties of NS7051 inferred from behavioural studies appear to contribute to
      its well tolerated antinociceptive profile in rats. However, unlike tramadol this
      did not correlate with the ability to increase hippocampal monoamine levels
      measured by microdialysis in anesthetised rats.

PMID- 18037452
TI  - Does angiotensin interact with dopaminergic mechanisms in the brain to modulate
      prepulse inhibition in mice?
AB  - Changes in the levels of angiotensin-converting enzyme (ACE) have been found in
      brains of schizophrenia patients, suggesting a possible involvement of
      angiotensin in the illness. Prepulse inhibition (PPI) is a measure of
      sensorimotor gating and is disrupted in patients with schizophrenia. In a
      previous study, a reduction of ACE activity, either in ACE knockout mice or after
      ACE inhibitor treatment, markedly inhibited the disruption of PPI caused by the
      dopamine receptor agonist, apomorphine. ACE is not specific for the angiotensin
      system and, therefore, in the present study we assessed pharmacological
      regulation of PPI in two other, more specific genetic mouse models of altered
      angiotensin activity. We used renin-enhancer knockout (REKO) mice, which display
      reduced renin activity, and neuron-specific enolase (NSE)-AT1A mice, which
      selectively over-express angiotensin AT1A receptors in the brain. Treatment of
      these mice with apomorphine, the dopamine releaser, amphetamine or the NMDA
      receptor antagonist, MK-801, significantly disrupted PPI. There was, however, no
      difference in these effects between the genotypes. These data suggest that
      genetically induced changes in the activity of the angiotensin system do not
      alter regulation of PPI in mice. Our previous results on the effects of reduced
      ACE activity could be explained by mechanisms other than angiotensin, such as
      effects on enkephalin or bradykinin metabolism.

PMID- 18037454
TI  - Planning, decision-making and the COMT rs4818 polymorphism in healthy males.
AB  - Recent evidence suggests that a synonymous polymorphism within the COMT gene
      (rs4818 C/G) accounts for a greater variation of COMT activity compared to the
      functional Val158Met polymorphism. This is the first study on the effects of the
      rs4818 C/G polymorphism on cognition. One hundred and seven healthy males were
      tested with the Stockings of Cambridge (SoC) and the Iowa Gambling Task (IGT) and
      then grouped according to their COMT rs4818 C/G status into three groups (G/G,
      C/G, C/C). ANOVAs showed that C/C individuals had the best performance in the
      SoC, G/G the worse, while C/G were intermediate. G/G individuals had strikingly
      better performance in the IGT compared to the other two groups and their
      performances in the two tasks were inversely related. These results show that the
      rs4818 C/G polymorphism imparts strong and differential effects on PFC functions.
      Low prefrontal dopamine levels are disadvantageous for planning in non-emotional
      problem solving but lead to optimal effects in emotionally informed decision
      making. While high prefrontal dopamine levels may be advantageous for non
      emotional problem solving, they lead to disadvantageous choices when decision
      making depends on processing of emotional feedback.

PMID- 18037453
TI  - Data-driven clustering reveals a fundamental subdivision of the human cortex into
      two global systems.
AB  - Global organizational principles are critical for understanding cortical
      functionality. Recently, we proposed a global sub-division of the posterior
      cortex into two large-scale systems. One system, labeled extrinsic, comprises the
      sensory-motor cortex, and is associated with the external environment. The second
      system, labeled intrinsic, overlaps substantially with the previously described
      "default-mode" network, and is likely associated with inner-oriented processing.
      This global partition of the cerebral cortex emerged from hemodynamic imaging
      data the analysis of which was constrained by pre-determined hypotheses. Here we
      applied a hypothesis-free, unsupervised two-class clustering algorithm (k-means)
      to a large set of fMRI data. The two clusters delineated by this unsupervised
      hypothesis-free procedure showed high anatomical consistency across individuals,
      and their cortical topography coincided largely with the previously determined
      extrinsic and intrinsic systems. These new clustering-based results confirm that
      the intrinsic-extrinsic subdivision constitutes a fundamental cortical divide.

PMID- 18037455
TI  - Is there continuity between categorical and coordinate spatial relations coding?
      Evidence from a grid/no-grid working memory paradigm.
AB  - We ask the question whether the coding of categorical versus coordinate spatial
      relations depends on different neural networks showing hemispheric specialization
      or whether there is continuity between these two coding types. The 'continuous
      spatial coding' hypothesis would mean that the two coding types rely essentially
      on the same neural network consisting of more general-purpose processes, such as
      visuo-spatial attention, but with a different weighting of these general
      processes depending on exact task requirements. With event-related fMRI, we have
      studied right-handed male subjects performing a grid/no-grid visuo-spatial
      working memory task inducing categorical and coordinate spatial relations coding.
      Our data support the 'continuous spatial coding' hypothesis, indicating that,
      while based on the same fronto-parieto-occipital neural network than categorical
      spatial relations coding, the coding of coordinate spatial relations relies more
      heavily on attentional and executive processes, which could induce hemispheric
      differences similar to those described in the literature. The results also show
      that visuo-spatial working memory consists of a short-term posterior store with a
      capacity of up to three elements in the parietal and extrastriate cortices. This
      store depends on the presence of a visible space categorization and thus can be
      used for the coding of categorical spatial relations. When no visible space
      categorization is given or when more than three elements have to be coded,
      additional attentional and executive processes are recruited, mainly located in
      the dorso-lateral prefrontal cortex.

PMID- 18037456
TI  - Two visual systems re-viewed.
AB  - The model proposed by the authors of two cortical systems providing 'vision for
      action' and 'vision for perception', respectively, owed much to the inspiration
      of Larry Weiskrantz. In the present article some essential concepts inherent in
      the model are summarized, and certain clarifications and refinements are offered.
      Some illustrations are given of recent experiments by ourselves and others that
      have prompted us to sharpen these concepts. Our explicit hope in writing our book
      in 1995 was to provide a theoretical framework that would stimulate research in
      the field. Conversely, well-designed empirical contributions conceived within the
      framework of the model are the only way for us to progress along the route
      towards a fully fleshed-out specification of its workings.

PMID- 18037457
TI  - The role of adipose tissue dysfunction in the pathogenesis of obesity-related
      insulin resistance.
AB  - Research of the past decade has increased our understanding of the role adipose
      tissue plays in health and disease. Adipose tissue is now recognized as a highly
      active metabolic and endocrine organ. Adipocytes are of importance in buffering
      the daily influx of dietary fat and exert autocrine, paracrine and/or endocrine
      effects by secreting a variety of adipokines. The normal function of adipose
      tissue is disturbed in obesity, and there is accumulating evidence to suggest
      that adipose tissue dysfunction plays a prominent role in the development and/or
      progression of insulin resistance. Obese individuals often have enlarged
      adipocytes with a reduced buffering capacity for lipid storage, thereby exposing
      other tissues to an excessive influx of lipids, leading to ectopic fat deposition
      and insulin resistance in situations where energy intake exceeds energy
      expenditure. In addition, adipose tissue blood flow is decreased in obesity. This
      impairment may affect lipid handling in adipose tissue and, thereby, further
      contribute to excessive fat storage in non-adipose tissues. On the other hand,
      adipose tissue hypoperfusion may induce hypoxia in this tissue. Adipose tissue
      hypoxia may result in disturbances in adipokine secretion and increased
      macrophage infiltration in adipose tissue, events that are frequently observed in
      obesity. In this review, it is discussed how enlarged adipocytes, an impaired
      blood flow through adipose tissue, adipose tissue hypoxia, adipose tissue
      inflammation and macrophage infiltration are interrelated and may induce insulin
      resistance.

PMID- 18037458
TI  - Onset of sexual maturation in female mice as measured in behavior and fertility:
      Interactions of exposure to males, phytoestrogen content of diet, and ano-genital
      distance.
AB  - Age of puberty was examined in female mice through non-invasive behavioral and
      fertility measures, in relationship to ano-genital distance, phytoestrogen
      content of diet, and exposure to males post-weaning. Throughout gestation and
      post-natal development, females were exposed to a regular diet or one that was
      nutritionally similar but deficient in phytoestrogens. After segregation at
      weaning on the basis of a short or long ano-genital distance index (AGDI), an
      indirect measure of in utero androgen exposure, females were housed alone or
      underneath two outbred adult males for two weeks. Subsequently, an outbred male
      was placed in the cage of each developing female, and mating behavior, escape
      attempts, biting gestures, and boxing postures were recorded. Next, females were
      monitored for the occurrence of a copulatory plug and allowed to bear young, with
      pregnancy and litters monitored up to weaning. Male-exposed females fed a regular
      diet were immediately sexually receptive when housed directly with males, and
      their conceptions occurred earlier than did those of other females. Subjects fed
      a diet deficient in phytoestrogens were least likely to show sexual receptivity.
      Male-exposed females with longer AGDI displayed more escape attempts in the
      presence of males, regardless of diet. Once inseminated, most females carried to
      term and the majority of pups survived until weaning. These data suggest that
      phytoestrogens and AGDI interact with exposure to males in determining age at
      onset of puberty.

PMID- 18037459
TI  - Evidence of bovine immunodeficiency virus (BIV) infection: serological survey in
      Argentina.
AB  - This is the first report of serological evidence for bovine immunodeficiency
      virus (BIV) infection in Argentina. The analysis was performed in 589 dairy
      bovine sera samples, applying indirect enzyme-linked immunosorbent assay (I
      ELISA) using a synthetic antigen (transmembrane peptide, TM) and
      Immunofluorescent assay (IFA). In this study, 9 dairy herds from 4 Argentinian
      provinces were evaluated and 12% of the animals tested positive for BIV. Seven of
      the 9 herds tested were BIV seropositive and the percentage of BIV seropositive
      animals in the herds ranged from 2% to 42%. Direct detection of BIV provirus
      applying nested PCR was not conclusive. Antibody detection against bovine
      leukemia virus (BLV) in all sera was also performed applying immunodiffusion (ID)
      assay and 59% resulted seropositive. Statistical analysis of the results was
      carried out and possible evidence of association between BIV and BLV infection
      was considered. Future studies should be performed including local field isolates
      strains of BIV.

PMID- 18037460
TI  - Expression profile of myostatin mRNA during the embryonic organogenesis of
      domestic chicken (Gallus gallus domesticus).
AB  - Myostatin is a potent growth and differentiation factor involved in skeletal
      muscle tissue formation in vertebrates. However, recent studies in chicken embryo
      suggested that the myostatin was expressed even before the establishment of
      myogenic lineage. No studies have thus far been reported in birds to define the
      role of myostatin during the embryonic organogenesis. The present experiment was
      designed for studying the expression profiles of myostatin mRNA in the chicken
      liver, heart, brain, and intestine during their morphogenesis, using real-time
      PCR. The myostatin mRNA expression was significantly upregulated in liver during
      E15-E18. Similar results were observed during the development of chicken heart.
      In brain, the expression of myostatin was upregulated from E4 onwards. In
      intestine, the expression of myostatin was significantly increased many folds on
      E9-E18. Therefore, the increase in myostatin expression might be related to the
      growth of liver and heart on days E12-E18; morphogenesis and growth of brain
      during E15-E18; and morphogenesis and differentiation of intestine during E9-E18.
      In the present study, the tissue-specific expression of myostatin gene in chicken
      is similar to fishes, but different from that in mammals. Further, the inspection
      of chicken genome also suggested that there is no differentiation of GDF-8 and 
      11. A recent finding suggests that the chicken myostatin gene is closely related
      to mammals than fishes. Therefore, we propose that the chicken myostatin gene
      might have diverged in its function between teleosts and mammals. Indeed it is
      possible that its function might have only become fully differentiated to serve
      as a control of muscle mass in mammals.

PMID- 18037461
TI  - Strategy for the detection and differentiation of Mycobacterium avium species in
      isolates and heavily infected tissues.
AB  - The members of Mycobacterium avium species, comprising M. avium subsp.
      paratuberculosis, M. a. hominissuis, M. a. avium, M. a. silvaticum, are currently
      the most prevalent opportunistic pathogenic mycobacteria causing mycobacterial
      infection in animals and humans. The ability to distinguish between these
      subspecies is of relevance for proper diagnosis and control programmes of the
      diseases. The aim of this study was to design a fast and specific PCR strategy
      for the detection and differentiation of M. avium subspecies from the solid plate
      cultures for use in routine veterinary diagnosis. We have developed a multiplex
      PCR based on IS900, IS901, IS1245 and the dnaJ gene. This method allows the
      detection of M. a. paratuberculosis, M. a. hominissuis and M. a. avium/M. a.
      silvaticum in one PCR reaction and theoretically enables mixed infections of M.
      a. paratuberculosis and M. a. avium or M. a. paratuberculosis and M. a.
      hominissuis to be revealed. The sensitivity of this multiplex PCR is 10(3)CFU for
      each bacterial strain in one PCR reaction, which also enabled the use of this
      test directly for DNA isolated from the tissue of the heavily infected sheep.

PMID- 18037462
TI  - B chain is a functional subunit of beta-bungarotoxin for inducing apoptotic death
      of human neuroblastoma SK-N-SH cells.
AB  - beta-Bungarotoxin (beta-Bgt), a presynaptic phospholipase A(2) (PLA(2))
      neurotoxin isolated from the venom of Bungarus multicinctus, consists of A chain
      and B chain. The goal of the present study is to explore the functional
      contribution of the two subunits to the toxicity of beta-Bgt. beta-Bgt was found
      to induce apoptotic death of SK-N-SH cells via elevating intracellular Ca(2+) and
      intracellular ROS production. Moreover, an activation of p38 MAPK was associated
      with the cytotoxicity of beta-Bgt. SB202190 (p38 MAPK inhibitor), N
      acetylcysteine (antioxidant reagent), 1,2-bis(2-aminophenoxy)ethane-N,N,N,N
      tetraacetic acid (BAPTA) (Ca(2+) chelator) and the inhibitors of Ca(2+) release
      from intracellular depots (ruthenium red and 2-aminoethoxydiphenyl borate)
      effectively attenuated the cytotoxicity of beta-Bgt. In sharp contrast to the
      inability of A chain, B chain was able to induce cytotoxic effects on SK-N-SH
      cells as beta-Bgt did. Abolishment of PLA(2) activity did not significantly alter
      the cytotoxic activity of beta-Bgt. MK801 (an NMDA receptor antagonist),
      antibodies against NMDA receptor and 4-aminopyridine (a potassium channel
      blocker) markedly reduced the cytotoxic effects of beta-Bgt, B chain and
      catalytically inactivated beta-Bgt. Moreover, antibodies against NMDA receptor
      blocked the binding of rhodamine-labeled beta-Bgt to SK-N-SH cells. Taken
      together, our data indicate that B chain is a functional subunit responsible for
      the cytotoxicity of beta-Bgt, and suggest that the cytotoxicity of beta-Bgt is
      mediated by NMDA receptor and potassium conductance.

PMID- 18037463
TI  - Inhibitory effect of cyclic terpenes (limonene, menthol, menthone and thymol) on
      Fusarium verticillioides MRC 826 growth and fumonisin B1 biosynthesis.
AB  - The minimum inhibitory concentration (MIC) of cyclic terpenes (limonene, menthol,
      menthone and thymol) against Fusarium verticillioides MRC 826 was assessed by
      using the semisolid agar antifungal susceptibility (SAAS) technique. Limonene,
      menthol, menthone and thymol were evaluated at final concentrations of 25, 50,
      75, 150, 200, 250, 500 and 1000 microL/L of culture medium. Limonene and thymol
      showed the highest inhibitory effects on F. verticillioides development. Thus,
      the effects of monoterpenes on fumonisin B1 (FB1) biosynthesis were evaluated by
      using corn grain (Zea mays) as substrate. The monoterpenes were inserted on maize
      1 day before inoculation with a conidial suspension of F. verticillioides to give
      final concentrations of 75 ppm. At this concentration, thymol was the most active
      inhibitor on FB1 biosynthesis.

PMID- 18037464
TI  - Conservation of inner domain modules in the surface envelope glycoproteins of an
      ancient rabbit lentivirus and extant lentiviruses and betaretroviruses.
AB  - The consensus sequence of endogenous lentiviral elements in the genome of
      European rabbits (RELIK) was used to extend a model of conserved lentiviral and
      betaretroviral surface envelope glycoprotein (SU) inner domain structures. Here
      it is shown that nearly all the inner domain elements of human and simian
      immunodeficiency virus gp120 mediating conformational changes upon CD4 binding
      were conserved in the SU of RELIK. Many of these inner domain elements and a
      carboxy-terminal region outside the gp120 core are also conserved in the SU of
      other lentiviruses and betaretroviruses, suggesting conserved mechanisms of SU
      conformational changes induced by receptor binding.

PMID- 18037465
TI  - Photocatalytic inactivation of Cryptosporidium parvum with TiO(2) and low
      pressure ultraviolet irradiation.
AB  - This study investigated the efficacy of low-pressure ultraviolet (UV) irradiation
      and the synergistic effect of UV/titanium dioxide (TiO(2)) photocatalysis on
      Cryptosporidium parvum oocyst inactivation. At UV doses of 2.7, 8.0, and
      40mJ/cm(2), oocyst inactivation was 1.3, 2.6, and 3.3log(10), respectively.
      Reactive oxygen species (ROS) generated by longwave UV radiation (>315nm) and
      TiO(2) achieved less than 0.28-log inactivation. However, the synergistic effect
      of germicidal (254nm) UV and TiO(2) resulted in 2-log and 3-log oocyst
      inactivation with 4.0 and 11.0mJ/cm(2), respectively. Therefore, using TiO(2) in
      combination with UV reduced the dose requirement for 3-log inactivation by 56%.
      An approximate 1-log decrease in inactivation of oocysts was observed with
      nanopure water in comparison to buffered water, whereas changes in pH from 6 to 8
      had little effect on the photocatalytic inactivation of oocysts in either matrix
      (P>0.1).

PMID- 18037466
TI  - Oxidation of MC-LR and -RR with chlorine and potassium permanganate: toxicity of
      the reaction products.
AB  - Toxin-producing cyanobacteria are abundant in surface waters used as drinking
      water resources. Microcystins (MC) produced by certain cyanobacteria present
      acute and chronic toxicity, and their removal in drinking water treatment
      processes is of increasing concern. Previous studies have demonstrated that
      chlorine and potassium permanganate are feasible oxidants for the removal of MCs
      present in drinking water resources, although the oxidation might lead to toxic
      oxidation products. In this paper, the toxicity of the oxidation products of MC
      LR and -RR has been studied using protein phosphatase 1 inhibition assay (PPIA).
      The HPLC and ELISA analyses correlated with the PPIA results for both toxins. The
      samples containing the oxidation products were fractionated by HPLC and the
      toxicity of the fractions was tested with PPIA. The results revealed that protein
      phosphatase 1 inhibition emerged only from intact MC, while the oxidation
      products were non-toxic. Similar results were obtained in experiments performed
      in natural waters: no reaction products or interactions exhibiting protein
      phosphatase 1 inhibition were detected.

PMID- 18037467
TI  - The role of starvation on Escherichia coli adhesion and transport in saturated
      porous media.
AB  - The influence of bacterial starvation on cell transport has been examined using
      two Escherichia coli isolates: one from human (HU) and one from dairy cattle
      (DC). To better understand the fate of starved bacteria, experiments were
      conducted in a packed bed column using cells that had been incubating at room
      temperature without nutrients for 6, 12, and 18h, as well as cells, which had not
      been starved (referred to as time zero). Complimentary cell characterization
      techniques were conducted to evaluate the hydrophobicity, mobility, size, and
      surface charge density of the cells at the conditions considered. It was observed
      that non-starved HU cells were more adhesive than starved HU cells. This behavior
      is attributed to the relatively high hydrophobicity of the starved cells, which
      resulted from greater extracellular polymeric substance (EPS) presence. Non
      starved DC cells were also the most adhesive whereas 18h starved cells were the
      least adhesive, although cell characterization results did not correlate to
      transport trends like HU cells. For both isolates, the cells after 6h of
      starvation showed high levels of sugar relative to protein in the EPS.
      Additionally, following 6h of starvation, the cells did not follow expected
      transport trends as anticipated from the cellular characterization. Our results
      suggest transport behavior of environmental E. coli isolates differs in terms of
      isolate host and starvation conditions. Possible mechanisms responsible for this
      are changes in key cell surface characteristics and synthesis of starvation
      induced proteins. This study highlights the importance of consistency in
      bacterial preparation for experimental studies and has considerable implications
      for future evaluation and prediction of E. coli fate in subsurface environments.

PMID- 18037468
TI  - Removal of heavy metals and arsenic from contaminated soils using bioremediation
      and chelant extraction techniques.
AB  - A combined chemical and biological treatment scheme was evaluated in this study
      aiming at obtaining the simultaneous removal of metalloid arsenic and cationic
      heavy metals from contaminated soils. The treatment involved the use of the iron
      reducing microorganism Desulfuromonas palmitatis, whose activity was combined
      with the chelating strength of EDTA. Taking into consideration that soil iron
      oxides are the main scavengers of As, treatment with iron reducing microorganisms
      aimed at inducing the reductive dissolution of soil oxides and thus obtaining the
      release of the retained As. The main objective of using EDTA was the removal of
      metal contaminants, such as Pb and Zn, through the formation of soluble metal
      chelates. Experimental results however indicated that EDTA was also indispensable
      for the biological reduction of Fe(III) oxides. The bacterial activity was found
      to have a pronounced positive effect on the removal of arsenic, which increased
      from the value of 35% obtained during the pure chemical treatment up to 90% in
      the presence of D. palmitatis. In the case of Pb, the major part, i.e.
      approximately 85%, was removed from soil with purely chemical mechanisms, whereas
      the biological activity slightly improved the extraction, increasing the final
      removal up to 90%. Co-treatment had negative effect only for Zn, whose removal
      was reduced from 80% under abiotic condition to approximately 50% in the presence
      of bacteria.

PMID- 18037469
TI  - The effects of exogenous plant growth regulators in the phytoextraction of heavy
      metals.
AB  - The term "assisted phytoextraction" usually refers to the process of applying a
      chemical additive to contaminated soil in order to increase the metal uptake by
      crop plants. In this study three commercially available plant growth regulators
      (PGRs) based on cytokinins (CKs) were used to boost the assisted phytoextraction
      of Pb and Zn in contaminated soil collected from a former manufactured gas-plant
      site. The effects of EDTA treatment in soil and PGR treatment in leaves of
      Helianthus annuus were investigated in terms of dry weight biomass, Pb and Zn
      accumulation in the upper parts of the plants, Pb and Zn phytoextraction
      efficiency and transpiration rate. Metal solubility in soil and its subsequent
      accumulation in shoots were markedly enhanced by EDTA. The combined effects of
      EDTA and cytokine resulted in an increase in the Pb and Zn phytoextraction
      efficiency (up to 890% and 330%, respectively, compared to untreated plants) and
      up to a 50% increase in foliar transpiration. Our results indicate that exogenous
      PGRs based on CKs can positively assist the phytoextraction increasing the
      biomass production, the metal accumulation in shoots and the plant transpiration.
      The observed increase in biomass could be related to its action in stimulation of
      cell division and shoot initiation. On the other hand, the increase in metal
      accumulation in upper parts of plant could be related to both the role of PGRs in
      the enhancement of plant resistance to stress (as toxic metals) and the increase
      in transpiration rate, i.e. flux of water-soluble soil components and
      contaminants by the regulation of stomatal opening.

PMID- 18037470
TI  - Levels and spatial distribution of chlorophenols - 2,4-dichlorophenol, 2,4,6
      trichlorophenol, and pentachlorophenol in surface water of China.
AB  - The chlorophenol pollutants (CPs) have been reported to occur at relatively high
      concentrations in some Chinese waters. To map the distribution of CPs in the
      surface water throughout China, samples were collected from over 600 sites in the
      seven major watersheds and three drainage areas. The samples were analyzed for
      the representative CPs including 2,4-dichlorophenol, 2,4,6-trichlorophenol, and
      pentachlorophenol. In general, it was observed that 2,4-dichlorophenol and 2,4,6
      trichlorophenol were more frequently detected at higher concentrations in the
      rivers of North China compared with those of South China. High concentration
      sites of 2,4-dichlorophenol and 2,4,6-trichlorophenol mainly occurred in the
      Yellow River, Huaihe River, and Haihe River watersheds, while pentachlorophenol
      contamination mainly occurred in the Yangtze River watershed. The
      pentachlorophenol was the most ubiquitous CPs being detected in 85.4% of samples
      (median=50.0ngl(-1); range <1.1-594.0ngl(-1)), 2,4-dichlorophenol was detected in
      51.3% (median=5.0ngl(-1); range <1.1-19960.0ngl(-1)) and the 2,4,6
      trichlorophenol was detected in 54.4% of water samples (median=2.0ngl(-1), range
      <1.4-28650.0ngl(-1)). The results of this investigation indicated that 2,4
      dichlorophenol and 2,4,6-trichlorophenol contaminations of Yellow River, Huaihe
      River, and Haihe River watersheds were of particular concern, while the
      pentachlorophenol contamination mainly occurred in the Yangtze River watershed.
      These results showed that CPs contamination in the surface water of China was
      similar to other places of the world.

PMID- 18037471
TI  - Comparison of arsenic resistance in Mediterranean woody shrubs used in
      restoration activities.
AB  - Myrtus communis, Arbutus unedo and Retama sphaerocarpa are Mediterranean shrubs
      widely used in revegetation of semiarid degraded soils. The aim of this work is
      to study the resistance of these plants to arsenic under controlled conditions,
      in order to evaluate their potential use in revegetation and/or phytoremediation
      of As-polluted soils. R. sphaerocarpa showed higher resistance to As than M.
      communis or A. unedo according to its higher EC50, P status and P/As molar ratio
      in both, roots and shoots, and the lower increases in lipid peroxidation and
      decrease of chlorophyll levels in response to arsenic, while the highest arsenate
      sensitivity was obtained for A. unedo. Arsenic was mainly retained in roots, and,
      although M. communis accumulated higher arsenic amounts than the other two
      species, R. sphaerocarpa showed the highest root to shoot transfer. Most of the
      studied parameters (chlorophylls, MDA and total thiols) showed significant
      correlation with arsenic concentration in roots and leaves of plants, so they can
      be useful indexes in the diagnosis of arsenic toxicity in these species.
      According to our results, both M. communis and R. sphaerocarpa could be used in
      the revegetation of moderately arsenic contaminated sites.

PMID- 18037472
TI  - Age at first molar emergence in Lufengpithecus lufengensis and its implications
      for life-history evolution.
AB  - The late Miocene hominoid Lufengpithecus from Yunnan Province, China, is crucial
      for understanding hominoid evolution in Asia. Given that age at first permanent
      molar emergence is a key life-history trait in primates, the present study
      determined the age at death of the Lufengpithecus lufengensis juvenile PA868,
      which was in the process of erupting its first molar. Using a perikymata
      periodicity of 7-11 days, along with estimation of cusp formation time and the
      postnatal delay of crown mineralization, perikymata counts obtained from the
      permanent central incisor and canine germs indicate that the age at death of
      PA868 was 2.4-4.5 years based on the central incisor germ, and 2.5-4.7 years
      based on the canine germ. The age at the first molar emergence was actually
      slightly younger (by about 0.3 years), as demonstrated by tiny wear facets on
      this tooth, which indicate that gingival emergence had occurred sometime before
      death. The average age at first molar emergence of Lufengpithecus lufengensis
      PA868 is estimated to be 3.2-3.3 years, with a range of 2.1-4.4 years. In
      comparison to extant primates and other fossil hominoids, the life history of
      Lufengpithecus lufengensis is similar to that of extant great apes and the
      Miocene hominoids Afropithecus turkanensis and Sivapithecus parvada, as well as
      Plio-Pleistocene Australopithecus, and different from monkeys, gibbons, and
      modern humans.

PMID- 18037473
TI  - Radiocarbon observations in atmospheric CO2: determining fossil fuel CO2 over
      Europe using Jungfraujoch observations as background.
AB  - Monthly mean 14CO2 observations at two regional stations in Germany (Schauinsland
      observatory, Black Forest, and Heidelberg, upper Rhine valley) are compared with
      free tropospheric background measurements at the High Alpine Research Station
      Jungfraujoch (Swiss Alps) to estimate the regional fossil fuel CO2 surplus at the
      regional stations. The long-term mean fossil fuel CO2 surplus at Schauinsland is
      1.31+/-0.09 ppm while it is 10.96+/-0.20 ppm in Heidelberg. No significant trend
      is observed at both sites over the last 20 years. Strong seasonal variations of
      the fossil fuel CO2 offsets indicate a strong seasonality of emissions but also
      of atmospheric dilution of ground level emissions by vertical mixing.

PMID- 18037474
TI  - Comparison between real time and flask measurements of atmospheric O2 and CO2
      performed at the High Altitude Research Station Jungfraujoch, Switzerland.
AB  - First real time CO2 and O2 measurements on the High Altitude Research Station
      Jungfraujoch (Switzerland) are compared with corresponding flasks samples.
      Whereas CO2 measurements show a good agreement, O2 compares only moderately. Real
      time O2 measurements are performed using two different methods, i.e. by
      paramagnetic and fuel cells. Fuel cell values exhibit significantly higher
      scatter, but they compare acceptably well with the paramagnetic values when
      averaging over 228 min (20 point running mean). Continuous measurements are
      powerful in many respects in contrast to spot-like flask sampling. They help to
      set up data selection criteria and to improve the robustness of trend
      calculations. Further, real time measurements help to partition the anthropogenic
      CO2 increase into ocean and terrestrial biosphere for short-time variations of
      minutes, hours, days, which are not covered by flask sampling.

PMID- 18037475
TI  - Microbial and "de novo" transformation of dicarboxylic acids by three airborne
      fungi.
AB  - Micro-organisms and organic compounds of biogenic or anthropogenic origins are
      important constituents of atmospheric aerosols, which are involved in atmospheric
      processes and climate change. In order to investigate the role of fungi and their
      metabolisation activity, we collected airborne fungi using a biosampler in an
      urban location of Montreal, Quebec, Canada (45 degrees 28' N, 73 degrees 45' E).
      After isolation on Sabouraud dextrose agar, we exposed isolated colonies to
      dicarboxylic acids (C(2)-C(7)), a major group of organic aerosols and monitored
      their growth. Depending on the acid, total fungi numbers varied from 35 (oxalic
      acid) to 180 CFU/mL (glutaric acid). Transformation kinetics of malonic acid,
      presumably the most abundant dicarboxylic acid, at concentrations of 0.25 and
      1.00 mM for isolated airborne fungi belonging to the genera Aspergillus,
      Penicillium, Eupenicillium, and Thysanophora with the fastest transformation rate
      are presented. The initial concentration was halved within 4.5 and 11.4 days.
      Other collected fungi did not show a significant degradation and the malonic acid
      concentration remained unchanged (0.25 and 1.00 mM) within 20 days. Degradation
      of acid with formation of metabolites was followed using high performance liquid
      chromatography-ultraviolet detection (HPLC/UV) and gas chromatography-mass
      spectrometry (GC/MS), as well as monitoring of (13)C labelled malonic acid
      degradation with solid-state nuclear magnetic resonance spectroscopy (NMR). Using
      GC/MS we identified two processes driving chemical modifications of organic
      aerosol solutions: (I) formation of metabolites within several days, and (II)
      rapid release (< or =2 min) of organic molecules from fungal species upon the
      insertion of taxa in organic aerosol solutions. Metabolites included aromatic
      compounds and alcohols (e.g. trimethylbenzene and butanol). Potential atmospheric
      implications of our results are discussed.

PMID- 18037476
TI  - Vertical distributions of SO(2) and NO(2) in the lower atmosphere in Beijing
      urban areas, China.
AB  - Measurements of SO(2) and NO(2) were conducted from January to March 2001 and
      August 2003 at a 325 m meteorological tower in Beijing. The concentrations of
      SO(2) and NO(2) observed by passive samplers at ten heights showed complex
      vertical distributions in winter and summer. The vertical profiles of pollutants
      were influenced by source emissions, meteorological conditions, urban canopy and
      other factors. The comparison analysis of winter and summer pollutant
      concentrations suggests that the decrease in SO(2) concentration was significant
      in summer, and the reduction of NO(2) was relatively not distinctive. Domestic
      heating and industrial sources were major sources of SO(2) in urban areas of
      Beijing. Differing from SO(2,) urban NO(2) was closely related to traffic
      emission. Meteorological evidence suggests that strong temperature inversions
      influence vertical distribution of air pollutants over urban Beijing. The high
      levels of SO(2) and NO(2) concentrations were due to the accumulation of
      pollutants resulting from the stable atmosphere prevalent during the measurement
      period. The vertical distributions of air pollutants were controlled and affected
      by atmospheric dynamical characteristics.

PMID- 18037477
TI  - Plasminogen activator inhibitor-1 levels in severe and morbid obesity. Effect of
      weight loss and influence of 4G/5G polymorphism.
AB  - INTRODUCTION: An association between an increase in plasminogen activator
      inhibitor type 1 and obesity has been described. It has also been shown that a
      decrease in adiposity has beneficial effects. However, less information is
      available regarding morbid obesity and hypofibrinolysis. The aim of the present
      study was to evaluate the effect of weight loss and the influence of the
      plasminogen activator inhibitor type 1 promoter 4G/5G genotype on plasminogen
      activator inhibitor type 1 levels in severe and morbid obesity. MATERIALS AND
      METHODS: Sixty-seven obese patients were studied before and three months after a
      weight reduction program, and compared with 67 controls. We determined
      plasminogen activator inhibitor type 1 antigen and activity levels, tissue type
      plasminogen activator antigen levels, 4G/5G genotype and biochemical parameters
      in both groups. RESULTS: A significant increase in plasminogen activator
      inhibitor type 1 antigen and activity was observed in obese patients in
      comparison with the control group (P<0.001). No significant differences in
      plasminogen activator inhibitor type 1 levels among 4G/5G genotypes were
      obtained. After weight loss, a significant decrease in plasminogen activator
      inhibitor type 1 antigen and activity was observed (P<0.001). A significant and
      positive correlation was observed in percentage changes in plasminogen activator
      inhibitor type 1 and body mass index (P=0.02). CONCLUSIONS: A decrease in body
      mass index in severe and morbid obesity shows a favourable effect on the
      fibrinolytic system due to a decrease in plasminogen activator inhibitor type 1
      levels. However, no influence of 4G/5G polymorphism has been observed in this
      setting.

PMID- 18037478
TI  - Phase III trial to evaluate the efficacy of maintaining hemoglobin levels above
      12.0 g/dL with erythropoietin vs above 10.0 g/dL without erythropoietin in anemic
      patients receiving concurrent radiation and cisplatin for cervical cancer.
AB  - PURPOSE: To determine whether maintaining HGB levels > or = 12.0 g/dL with
      recombinant human erythropoietin (R-HUEPO) compared to "standard" treatment
      (transfusion for HGB < or = 10.0 g/dL) improves progression-free survival (PFS),
      overall survival (OS) and local control (LC) in women receiving concurrent weekly
      cisplatin and radiation (CT/RT) for carcinoma of the cervix. In addition, to
      determine whether platinum-DNA adducts were associated with clinical
      characteristics or outcome. METHODS: Patients with stage IIB-IVA cervical cancer
      and HGB < 14.0 g/dL were randomly assigned to CT/RT+/-R-HUEPO (40,000 units s.c.
      weekly). R-HUEPO was stopped if HGB > 14.0 g/dL. Endpoints were PFS, OS and LC.
      Platinum-DNA adducts were quantified using immunocytochemistry assay in buccal
      cells. RESULTS: Between 08/01 and 09/03, 109 of 114 patients accrued were
      eligible. Fifty-two received CT/RT and 57 CT/RT+R-HUEPO. The study closed
      prematurely, with less than 25% of the planned accrual, due to potential concerns
      for thromboembolic event (TE) with R-HUEPO. Median follow-up was 37 months (range
      9.8-50.4 months). PFS and OS at 3 years should be 65% and 75% for CT/RT and 58%
      and 61% for CT/RT+R-HUEPO, respectively. TE occurred in 4/52 receiving CT/RT and
      11/57 with CT/RT+R-HUEPO, not all considered treatment related. No deaths
      occurred from TE. High-platinum adducts were associated with inferior PFS and LC.
      CONCLUSION: TE is common in cervical cancer patients receiving CT/RT. Difference
      in TE rate between the two treatments was not statistically significant. The
      impact of maintaining HGB level > 12.0 g/dL on PFS, OS and LC remains
      undetermined.

PMID- 18037479
TI  - Identification of antidepressant drug leads through the evaluation of marine
      natural products with neuropsychiatric pharmacophores.
AB  - The marine environment is a valuable resource for drug discovery due to its
      diversity of life and associated secondary metabolites. However, there is very
      little published data on the potential application of marine natural products to
      treat neuropsychiatric disorders. Many natural products derived from chemically
      defended organisms in the marine environment have pharmacophores related to
      serotonin or clinically utilized antidepressant drugs. Therefore, in the present
      study, compounds selected for their structural similarity to serotonin or
      established antidepressants were evaluated for antidepressant-like activity using
      the forced swim and tail suspension tests in mice. The antidepressant positive
      controls, citalopram (selective serotonin reuptake inhibitor) and despiramine
      (tricyclic antidepressant) both dose-dependently reduced immobility time in the
      forced swim and tail suspension tests. Two marine natural product compounds
      tested, aaptamine and 5,6-dibromo-N,N-dimethyltryptamine, also produced
      significant antidepressant-like activity in the forced swim test. In the tail
      suspension test, the antidepressant-like effects of 5,6-dibromo-N,N
      dimethyltryptamine were confirmed, whereas aaptamine failed to produce
      significant results. None of the tested compounds induced hyperlocomotion,
      indicating that nonspecific stimulant effects could not account for the observed
      antidepressant-like actions of the compounds. These studies highlight the
      potential to rationally select marine derived compounds for treating depression
      and other neuropsychiatric disorders.

PMID- 18037480
TI  - Public transit, obesity, and medical costs: assessing the magnitudes.
AB  - OBJECTIVE: This paper assesses the potential benefits of increased walking and
      reduced obesity associated with taking public transit in terms of dollars of
      medical costs saved and disability avoided. METHODS: I conduct a new analysis of
      a nationally representative U.S. transportation survey to gauge the net increase
      in walking associated with public transit usage. I translate minutes spent
      walking into energy expenditures and reductions in obesity prevalence, estimating
      the present value of costs and disability that may be avoided. RESULTS: Taking
      public transit is associated with walking 8.3 more minutes per day on average, or
      an additional 25.7-39.0 kcal. Hill et al. [Hill, J.O., Wyatt, H.R., Reed, G.W.,
      Peters, J.C., 2003. Obesity and the environment: Where do we go from here?
      Science 299 (5608), 853-855] estimate that an increase in net expenditure of 100
      kcal/day can stop the increase in obesity in 90% of the population. Additional
      walking associated with public transit could save $5500 per person in present
      value by reducing obesity-related medical costs. Savings in quality-adjusted life
      years could be even higher. CONCLUSIONS: While no silver bullet, walking
      associated with public transit can have a substantial impact on obesity, costs,
      and well-being. Further research is warranted on the net impact of transit usage
      on all behaviors, including caloric intake and other types of exercise, and on
      whether policies can promote transit usage at acceptable cost.

PMID- 18037481
TI  - Expression of progesterone and oestrogen receptors by early intrauterine equine
      conceptuses.
AB  - Progesterone and oestrogen play essential roles in the maintenance of pregnancy
      in eutherian mammals and are thought to exert their effects on the developing
      conceptus indirectly, via the endometrium. In some species, early embryos have
      themselves been shown to express steroid receptors, thereby suggesting that
      reproductive steroids may also influence embryonic development directly. The aim
      of this study was to determine whether early intrauterine equine conceptuses
      express either the classical intracellular progesterone (PR) and oestrogen
      receptors (ERalpha and ERbeta) or the more recently characterised membrane-bound
      progesterone receptors (PGRMC1 and mPR). Horse conceptuses recovered on days 7,
      10 and 14 after ovulation (n=8 at each stage) were examined for steroid receptor
      mRNA expression using quantitative rtPCR. Where commercial antibodies were
      available (PR, ERbeta), receptor localisation was examined immunohistochemically
      in day 10, 12, 14, 15 and 16 conceptuses (n=2 at each stage). mRNA for PR, PGRMC1
      and mPR was detected at all stages examined, but while PGRMC1 and mPR expression
      increased during the day 7-14 period, PR expression decreased. ERalpha mRNA was
      not detected at any stage examined, whereas ERbeta mRNA was detected in all day
      14, some day 10 and no day 7 conceptuses. Immunoreactive ERbeta receptors were
      localised to the trophectoderm of day 14-16 conceptuses; PR were not detected
      immunohistochemically in conceptus tissue. In summary, this study demonstrates
      that equine conceptuses express mRNA and, in the case of ERbeta, protein for
      steroid hormone receptors during the period encompassing rapid conceptus growth,
      differentiation and maternal pregnancy recognition.

PMID- 18037482
TI  - Presence of pro-lentiviral DNA in male sexual organs and ejaculates of small
      ruminants.
AB  - To be able to predict sexual transmissibility of small ruminant lenti viruses
      (SRLV), it is necessary to know whether or not the virus is excreted in the
      semen, and under what circumstances. Thus, this research focussed on establishing
      the presence of proviral DNA of SRLV in semen and in the male genital tract of
      small ruminants. After initial results established the presence of SRLV in serum,
      the emergence of proviral DNA of SRLV in semen and presence in blood in a group
      of naturally SRLV-infected individuals (13 rams and 4 bucks), was followed
      temporally using real-time polymerase chain reaction (PCR). The same animals were
      also systematically serologically monitored by enzyme-linked immuno sorbent assay
      (ELISA) during the breeding season (August-February). A triple monocyte
      macrophage count was performed on both blood and semen using a specific
      monoclonal antibody in conjunction with flow cytometry. The finding that
      epididymal semen and tissue samples of the testes, epididymides, ampullary,
      vesicular, prostate and bulbo-urethral glands all tested positive for the
      presence of proviral DNA indicates that various male sexual organs may contribute
      directly to shedding of proviral SRLV DNA in ejaculated semen. Our results
      suggest that small ruminants show intermittent shedding of proviral SRLV DNA into
      epididymal as well as ejaculated semen. They also demonstrate that a single PCR
      negative semen sample cannot be used as a diagnostic tool to predict that
      subsequent ejaculates will be SRLV-free. No significant relationship was found
      between numbers of monocytes and/or macrophages in blood or semen and the
      detection of proviral SRLV in ejaculates.

PMID- 18037483
TI  - Lipid peroxidation: control of cell proliferation, cell differentiation and cell
      death.
AB  - In recent years, it has become evident that lipid peroxidation is not only a
      mechanism for deterioration of alimentary oils and fats, but can occur even in
      living cells, both in pathological and physiological conditions. Through its
      aldehydic products, it can regulate several cellular processes, as proliferation,
      differentiation and apoptosis of normal and neoplastic cells. In this review we
      describe some recent findings obtained in these fields.

PMID- 18037484
TI  - Measurements of mitochondrial pH in cultured cortical neurons clarify
      contribution of mitochondrial pore to the mechanism of glutamate-induced delayed
      Ca2+ deregulation.
AB  - To clarify the role of the mitochondrial permeability transition pore (MPT) in
      the mechanism of the glutamate-induced delayed calcium deregulation (DCD) and
      mitochondrial depolarization (MD), we studied changes in cytosolic (pH(c)) and
      mitochondrial pH (pH(m)) induced by glutamate in cultured cortical neurons
      expressing pH-sensitive fluorescent proteins. We found that DCD and MD were
      associated with a prominent pH(m) decrease which presumably resulted from MPT
      opening. This pH(m) decrease occurred with some delay after the onset of DCD and
      MD. This argued against the hypothesis that MPT opening plays a dominant role in
      triggering of DCD. This conclusion was also supported by experiments in which
      Ca(2+) was replaced with antagonist of MPT opening Sr(2+). We found that in
      Sr(2+)-containing medium glutamate-induced delayed strontium deregulation (DSD),
      similar to DCD, which was accompanied by a profound MD. Analysis of the changes
      in pH(c) and pH(m) associated with DSD led us to conclude that MD in Sr(2+)
      containing medium occurred without involvement of the pore. In contrast, in
      Ca(2+)-containing medium such "non-pore mechanism" was responsible only for MD
      initiation while in the final stages of MD development the MPT played a major
      role.

PMID- 18037486
TI  - A not so Pacific voyage: the 'floating laboratory' of Nicolas Baudin.
AB  - Nicolas Baudin's voyage to Australia in 1800 was particularly fractious. Many
      officers and scientists deserted. When stories of mission mismanagement leaked
      back to France, Baudin's reputation--and the public reputation of the expedition
      as a whole--was left in tatters. All was not Baudin's fault, however. Scientific
      rivalries--disputes over credit and quarrels over mission priorities--undermined
      his mission from the start, and explain why his attempt to use a 'public' journal
      to foster teamwork backfired. Unable to control his floating laboratory's
      paperwork, Baudin became an 'invisible commander'. After the expedition returned,
      naturalist Francois Peron assumed credit for its work.

PMID- 18037485
TI  - Roles of p15Ink4b and p16Ink4a in myeloid differentiation and RUNX1-ETO
      associated acute myeloid leukemia.
AB  - Inactivation of p15(Ink4b) expression by promoter hypermethylation occurs in up
      to 80% of acute myeloid leukemia (AML) cases and is particularly common in the
      FAB-M2 subtype of AML, which is characterized by the presence of the RUNX1-ETO
      translocation in 40% of cases. To establish whether the loss of p15(Ink4b)
      contributes to AML progression in association with RUNX1-ETO, we have expressed
      the RUNX1-ETO fusion protein from a retroviral vector in hematopoietic progenitor
      cells isolated from wild-type, p15(Ink4b) or p16(Ink4a) knockout bone marrow.
      Analysis of lethally irradiated recipient mice reconstituted with RUNX1-ETO
      expressing cells showed that neither p15(Ink4b) or p16(Ink4a) loss significantly
      accelerated disease progression over the time period of one year post
      transplantation. Loss of p15(Ink4b) alone resulted in increased myeloid
      progenitor cell frequencies in bone marrow by 10-month post-transplant and a 19
      fold increase in the frequency of Lin(-)c-Kit(+)Sca-1(+) (LKS) cells that was not
      associated with expansion of long-term reconstituting HSC. These results strongly
      suggest that p15(Ink4b) loss must be accompanied by additional oncogenic changes
      for RUNX1-ETO-associated AML to develop.

PMID- 18037487
TI  - College Chemistry: how a textbook can reveal the values embedded in chemistry.
AB  - This paper explores the norms, values and ethical attitudes that Linus Pauling
      wanted to convey to his students in his famous textbook College Chemistry. In
      this classic textbook, Pauling aimed to introduce beginners into the world of
      chemistry by presenting chemistry as a systematic science based on a collection
      of empirical data and a recent theoretical framework. In doing so, he expressed
      his epistemic and didactic choices clearly. College Chemistry therefore offers an
      ideal opportunity to examine some of the norms at the core of chemistry's 'moral
      economy'.

PMID- 18037488
TI  - Blind ambition: Geoffroy St-Hilaire's theory of everything.
AB  - When Napoleon Bonaparte invaded Egypt in 1798, he took with him a group of
      savants to study the natural history, architecture, ancient history and society
      of Egypt. One young naturalist, Etienne Geoffroy Saint-Hilaire, went along and
      made his mark in the study of living and mummified animals, setting the course
      for his future successes and fame when he returned to Paris in 1801. But during
      his time in Egypt, when he was free to roam physically and intellectually, he
      formulated a radical, all-encompassing theory, which he claimed could explain all
      natural forces and processes in the world.

PMID- 18037489
TI  - Synthesis, characterization and antiproliferative activity of metal complexes
      with the Schiff base derived from the condensation 1:2 of 2,6-diformyl-4
      methylphenol and 5,6-diamino-1,3-dimethyluracil.
AB  - A series of mononuclear complexes with Co(II), Ni(II), Cu(II), Zn(II), Hg(II),
      Mo(VI) and Pd(II) containing the ligand derived from the 1:2 condensation of 2,6
      diformyl-4-methylphenol and 5,6-diamino-1,3-dimethyluracil (hereafter denoted as
      BDFDAAU) were synthesized. The complexes were characterized by elemental
      analysis, thermogravimetry (TG) and differential scanning calorimetry (DSC), IR,
      (1)H, (13)C and (15)N NMR, UV-visible-near IR (UV-VIS-NIR), EPR and magnetic
      measurements. The deprotonated ligand in the phenolic oxygen shows a symmetric
      tridentate coordination mode through the two azomethine nitrogen atoms and the
      phenolic oxygen atom whereas the coordination of the neutral ligand takes place
      through the phenolic oxygen atom and one azomethine nitrogen atom. In the Mo(VI)
      complex, the ligand is bideprotonated in the phenolic oxygen and an amino group
      from one uracil unit; so, the coordination mode changes again into an asymmetric
      way: phenolic oxygen atom, one azomethine nitrogen atom and the nitrogen atom
      from the deprotonated amino group. The antiproliferative behaviour against the
      five human tumor cell lines (human neuroblastoma NB69, human breast cancer MCF-7
      and EVSA-T, human glioma H4 and human bladder carcinoma cell line ECV) suggested
      a modulator behaviour, according to the concentration, of cell growth due to
      their estrogen-like characteristics.

PMID- 18037490
TI  - The influence of temperature on antiproliferative effects, cellular uptake and
      DNA platination of the clinically employed Pt(II)-drugs.
AB  - Cellular uptake of a drug is one of the most important factors influencing its
      pharmacodynamics and pharmacokinetics. Our laboratory has previously studied
      platinum uptake following cisplatin, carboplatin and oxaliplatin treatment at sub
      lethal doses of selected tumour cell lines. Here we report on the influence of
      temperature on dose-dependent antiproliferative effects, cellular uptake and DNA
      platination of these platinum-based drugs tested on MCF-7 human mammary carcinoma
      cell line. Inductively coupled plasma-mass spectrometry (ICP-MS) technique has
      been chosen to perform Pt determinations on cells treated with drug
      concentrations similar with those usually found in vivo in human plasma. The high
      sensitivity and analytical rapidity of this technique made possible to carry out
      a very large amount of Pt determinations (about 300) necessary for this study.
      Hyperthermia (43 degrees C) proved a synergistic effect with cisplatin on cell
      growth inhibition, while only an additive effect was demonstrated for carboplatin
      and oxaliplatin. This behaviour might be explained by the higher DNA platination
      ratio between data at 43 and 37 degrees C of cisplatin with respect to those of
      carboplatin and oxaliplatin.

PMID- 18037491
TI  - Synthesis, structural characterization, antiradical and antidiabetic activities
      of copper(II) and zinc(II) Schiff base complexes derived from salicylaldehyde and
      beta-alanine.
AB  - A series of copper(II) and zinc(II) complexes involving a tridentate O,N,O'-donor
      Schiff base derived from salicylaldehyde and beta-alanine {i.e. N-salicylidene
      beta-alanine(2-), (L)}, having the composition [Cu(2)(L)(2)(H(2)O)].H(2)O (1),
      [Cu(L)(H(2)O)](n) (2), and [Zn(L)(H(2)O)](n) (3), have been prepared and
      characterized by elemental analyses, UV-visible (UV-VIS), FT-IR and ESI-MS
      spectra, and thermal analyses. Complexes 1 and 2 have been investigated by single
      crystal X-ray analysis and also by temperature dependent magnetic susceptibility
      measurements (294-80K). All prepared complexes have been evaluated by the
      antiperoxynitrite activity assay and alloxan-induced diabetes model. The
      significant antioxidant and antidiabetic activities have been found in the case
      of both copper(II) complexes 1 and 2. In spite of first two complexes, the
      zinc(II) complex 3, as well as the potassium salt of the ligand (KHL) showed only
      insignificant protective effect against the tyrosine nitration in vitro.

PMID- 18037492
TI  - Kinetics and thermodynamics of complex formation with iron of a new series of
      dicatecholspermidine siderophore-like ligands.
AB  - This article deals with the kinetics and thermodynamics of complex formation
      between Fe(3+) and a series of four synthetic chelators of the 1,2
      dicatecholspermidine family (LA5, LA3, LE5 and LE3). LA5 and LA3 bear a
      carboxylic moiety linked to the central nitrogen by either a C(5) or a C(3)
      chain, whereas LE5 and LE3 bear an ethyl ester moiety. The following data concern
      LE5, LE3, LA5 and LA3, respectively. Each species undergoes four acid-base
      dissociations of the hydroxyls of the catechols with, for the two hydroxyls in
      position 1; average pK(2a)=7.30, 7.25, 7.45, 7.34 and, for the two hydroxyl in
      position 2; average pK(3a)=12.35, 12.65, 12.10, 12.60. The LA5 and LA3 species
      also undergo proton-dissociations of their carboxylic moieties; pK(1a)=5.20 and
      5.10. The four species form one-to-one iron complexes with, for the 1-hydroxyl;
      an average pK(22a)=2.65, 2.25, 2.95, 2.80, for the 2-hydroxyl; pK(33a)=5.20,
      5.40, 6.10, 5.40 and, for the carboxylic moieties; pK(11a)=3.90 and 4.45. In the
      vicinity of pH 5, Fe(3+) is rapidly exchanged between FeNta and the four ligands.
      This occurs with direct rate constants: k(1)=(1.3+/-0.1)x10(4), (1.4+/
      0.2)x10(4), (3.3+/-0.2)x10(4), (1.4+/-0.1)x10(4)M(-1)s(-1), and reverse rate
      constants: k(-1)=(7+/-0.5)x10(4), (9+/-1)x10(4), (1.15+/-0.15)x10(5), (7+/
      0.5)x10(4)M(-1)s(-1). The kinetic data, the pK(a) values of the free ligands,
      those of the iron complexes and the beta value of FeNta allow us to determine the
      affinity constants of the four ligands for iron: logbeta(1)=33, 34, 33, 34, and
      pFe=23.3, 24.6, 22.2, 24.3. This implies that these ligands of the
      dicatecholspermidine family may act as siderophores. They may also be used as
      drug carriers which can utilize the bacterial iron-acquisition paths.

PMID- 18037493
TI  - The incidence and microbial spectrum of ventilator-associated pneumonia after
      tracheotomy in a selective decontamination of the digestive tract-setting.
AB  - OBJECTIVES: Tracheotomy is considered to be an independent risk factor for
      ventilator-associated pneumonia (VAP). Antimicrobial prophylaxis, in particular
      with coverage of Pseudomonas aeruginosa, is presently advocated. Selective
      decontamination of the digestive tract (SDD) aims to prevent VAP in critically
      ill patients, including those after tracheotomy. We determined the incidence and
      microbial spectrum of VAP after tracheotomy in a SDD-setting. METHODS:
      Retrospective analysis of 231 tracheotomized patients during a 2-year period.
      RESULTS: Thirteen patients (5.6%) developed VAP. The median [IQR] day of onset
      was 8.0 [3.0-10.5] days after tracheotomy. The most predominant causative
      pathogen was Methicillin-sensitive Staphylococcus aureus (MSSA). Timing of
      tracheotomy was not different between patients developing VAP and those who did
      not. The type of tracheotomy (percutaneous or surgical, 84.6% versus 15.4%) had
      no significant influence on the incidence of VAP. CONCLUSIONS: The incidence of
      VAP after tracheotomy in a SDD-setting is low, with MSSA as the predominant
      causative pathogen. Accordingly, if antimicrobial prophylaxis is considered, it
      may be advisable to cover MSSA in an SDD-setting.

PMID- 18037494
TI  - Prenatal dysthymia versus major depression effects on the neonate.
AB  - Depressed pregnant women were classified as dysthymic or major depression
      disorder based on the Structured Clinical Interview for Depression and followed
      to the newborn period. The newborns of dysthymic versus major depression disorder
      mothers had a significantly shorter gestational age, a lower birthweight, shorter
      birth length and less optimal obstetric complications scores. The neonates of
      dysthymic mothers also had lower orientation and motor scores and more depressive
      symptoms on the Brazelton Neonatal Behavioral Assessment Scale. These findings
      were not surprising given the elevated cortisol levels and the inferior fetal
      measures including lower fetal weight, fetal length, femur length and abdominal
      circumference noted in our earlier study on fetuses of dysthymic pregnant women.

PMID- 18037495
TI  - Subgenual cingulate volumes in affected and unaffected offspring of bipolar
      parents.
AB  - BACKGROUND: Bipolar disorders (BD) have a strong genetic underpinning, yet no
      biological vulnerability markers for BD have been identified. Decreased volumes
      of subgenual cingulate (SGC) were replicated in familial bipolar patients.
      Presence of abnormality in unaffected subjects at genetic risk for an illness
      needs to be established before SGC volumes can be used as an endophenotype. This
      is the first study of SGC volumes in affected and unaffected subjects at familial
      risk for mood disorders. METHOD: High-risk participants were recruited from
      families multiply affected with BD. The high-risk sample included 13 affected and
      13 unaffected offspring of bipolar I parents, who were matched by age and sex
      with 31 controls without a personal or family history of psychiatric disorders.
      The expanded sample consisted of 24 unaffected, 19 affected subjects all with a
      first or second degree relative suffering from BD I or II. The age range for all
      subjects was 15-30 years. Subgenual cingulate volumes were measured on 1.5 T 3D
      anatomical MRI images using standard methods. RESULTS: We found comparable SGC
      volumes among unaffected, affected offspring of BD I parents and controls.
      Likewise no SGC abnormalities were found in the expanded sample of subjects with
      BD I or II relatives. Left SGC volumes in all groups were smaller than right SGC
      volumes without laterality by group interaction. The exclusion of 5 medicated
      subjects did not change the results. LIMITATIONS: Cross sectional design,
      inclusion of both bipolar I and bipolar II probands. CONCLUSIONS: Subgenual
      cingulate volume abnormalities were absent in unaffected or affected relatives of
      bipolar patients and thus did not meet criteria for endophenotype.

PMID- 18037496
TI  - Abnormal corpus callosum myelination in pediatric bipolar patients.
AB  - BACKGROUND: Decreased signal intensity in the corpus callosum, reported in adult
      bipolar disorder patients, has been regarded as an indicator of abnormalities in
      myelination. Here we compared the callosal signal intensity of children and
      adolescents with bipolar disorder to that of matched healthy subjects, to
      investigate the hypothesis that callosal myelination is abnormal in pediatric
      bipolar patients. METHODS: Children and adolescents with DSM-IV bipolar disorder
      (n=16, mean age+/-S.D.=15.5+/-3.4 y) and matched healthy comparison subjects
      (n=21, mean age+/-S.D.=16.9+/-3.8 y) underwent a 1.5 T MRI brain scan. Corpus
      callosum signal intensity was measured using an Apple Power Mac G4 running NIH
      Image1.62 software. RESULTS: Bipolar children and adolescents had significantly
      lower corpus callosum signal intensity for all callosal sub-regions (genu,
      anterior body, posterior body, isthmus and splenium) compared to healthy subjects
      (ANCOVA, all p<0.05, age and gender as covariates). LIMITATIONS: Relatively small
      sample size. CONCLUSIONS: Abnormalities in corpus callosum, probably due to
      altered myelination during neurodevelopment, may play a role in the
      pathophysiology of bipolar disorder among children and adolescents.

PMID- 18037498
TI  - Treatment of bipolar depression: an update.
AB  - This article attempts to summarize the current status of our knowledge and
      practice in the acute treatment and prophylaxis of bipolar depression. For
      prophylactic treatment, our knowledge about lithium firmly supports its
      usefulness against bipolar depression and its specific effectiveness for suicidal
      prevention. Valproic acid and carbamazepine could be effective, too, while
      lamotrigine which seems to be preferably effective against depression but not
      mania. The FDA has approved the olanzapine-fluoxetine combination and quetiapine
      monotherapy for the treatment of acute bipolar depression. The usefulness of
      antidepressants in bipolar depression is controversial both for acute and
      prophylactic treatment; guidelines suggest their cautious use and always in
      combination with an antimanic and mood stabilizer agent, because in some patients
      they may induce switching to mania or hypomania, mixed episodes and rapid
      cycling. Data on psychosocial intervention are restricted to the maintenance
      phase. Electroconvulsive therapy and transcranial magnetic stimulation are
      additional options for refractory patients. Bipolar depression seems to be a more
      difficult condition to treat than mania. Most patients need complex combination
      treatment although the published evidence on this type of treatment is limited.

PMID- 18037497
TI  - A comparison of baseline sociodemographic and clinical characteristics between
      major depressive disorder patients with and without diabetes: a STAR*D report.
AB  - BACKGROUND: Patients with major depressive disorder (MDD) have high rates of
      medical comorbidities which can impair MDD treatment. Yet little is known
      regarding associations between the presence of a serious comorbidity and MDD
      treatment. The purpose of this study was to examine the baseline sociodemographic
      and clinical characteristics of MDD outpatients with and without diabetes
      mellitus to evaluate possible associations between these characteristics and the
      presence of comorbid diabetes. METHODS: We gathered baseline sociodemographic and
      clinical data for 4041 participants with non-psychotic MDD who enrolled in the
      STAR*D, a large-scale depression treatment protocol, and made comparisons between
      participants with and without diabetes. RESULTS: Participants with diabetes were
      more likely to be male, older, black, Hispanic, unemployed, and have less
      education, a lower income, higher mental functioning, lower physical functioning,
      atypical features, increased appetite, psychomotor slowing and leaden paralysis,
      and were less likely to have concurrent alcohol abuse/dependence, mood reactivity
      or problems with concentration. We found no significant differences between
      groups regarding depression severity. LIMITATIONS: The primary limitation is the
      lack of a clinical diagnosis of diabetes. CONCLUSIONS: We found no difference in
      depression severity between participants with and without diabetes. Diabetes was
      associated with physical symptoms of depression. Thus treatments for these
      participants should be directed toward these symptoms.

PMID- 18037499
TI  - Evaluation and comparison of different versions of the Body Shape Questionnaire.
AB  - The Body Shape Questionnaire (BSQ) is a widely used scale to assess body
      dissatisfaction. Several short forms of the BSQ have been introduced. In the
      present study, the full-length 34-item version of the BSQ and seven derivations
      were evaluated. Factorial validity was analyzed by confirmatory factor analyses
      in a representative sample of German females (n=1080). Treatment sensitivity was
      evaluated in a sample of 43 women with bulimia nervosa who completed the BSQ
      before and after cognitive-behavioral therapy. While fit indices of the full
      length version of the BSQ were poor, three of the derivations had reasonable fit.
      If treatment sensitivity is considered, one of the short forms performed best.
      This derivation is one of the eight-item versions of the BSQ (suggested
      abbreviation: BSQ-8C). In conclusion, the present study presents the empirical
      background for choosing between eight different versions of the BSQ. Thus, it is
      no longer necessary for researchers and clinicians to make their choice based on
      subjective criteria. Nevertheless, research on the derivations of the BSQ as
      stand-alone questionnaires is needed.

PMID- 18037500
TI  - Programmed Death-1: from gene to protein in autoimmune human myasthenia gravis.
AB  - The key role of an inhibitory receptor, Programmed Death-1, has been evaluated in
      273 patients with autoimmune myasthenia gravis. At the genetic level, SNP's
      genotyping showed no significant association to the disease. Gene expressions in
      patients were not different from that in controls. Interestingly, at the cell
      surface protein level, there were significant elevated levels of PD-1 on T cells
      and its ligand PD-L1 on monocytes in the patients compared to controls. However,
      we could not demonstrate any secreted soluble forms of PD-1 among the patients
      and controls. Thus, our study shows PD-1 might have a natural regulatory property
      behind MG.

PMID- 18037502
TI  - Systemic immune aberrations in Alzheimer's disease patients.
AB  - The role of chronic inflammation in the pathogenesis of Alzheimer's disease (AD)
      has been implied in a plethora of studies. The objective of the present study was
      to evaluate the immune alterations and the immunological markers in patients
      suffering from AD. IL-1alpha, IL-2, IL-6, IL-8, IL-10, TNF-alpha cytokine and
      helper/inducer (CD4), suppressor/cytotoxic (CD8) T lymphocyte levels were
      investigated in patients with various degrees of cognitive impairment (mild
      moderate and severe stage), as well as in age-matched non demented controls.
      Cytokines were measured using the ELISA immunoassay method and lymphocytes using
      flow cytometry. Results showed a significant TNF-alpha increase in patients of
      severe stage serum compared to controls as well as a significant decrease of CD4
      lymphocyte subpopulation levels in patients of severe stage compared to those of
      mild-moderate stage patients and controls. No significant differences were
      observed on IL-1alpha, IL-2, IL-6, IL-8, IL-10 cytokine levels and on CD8,
      CD4/CD8 lymphocyte subpopulations levels between patients and controls neither
      between mild moderate and severe stage patients. CD4 lymphocyte subpopulation and
      cytokine IL-2 were revealed as having a significant relationship (positive and
      negative respectively) with the MMSE score of patients. Data suggest the
      existence of detectable changes of peripheral immune system in AD.

PMID- 18037501
TI  - Induction of experimental ataxic sensory neuronopathy in cats by immunization
      with purified SGPG.
AB  - IgM paraproteins in about 50% of the patients with neuropathy associated with IgM
      gammopathy react with carbohydrate moieties in myelin-associated glycoprotein
      (MAG) and in sulfated glucuronic glycolipids (SGGLs) in human peripheral nerves.
      However, the role of anti-MAG/SGGL antibodies in the pathogenesis of neuropathy
      remains unclear. In order to induce an animal model of neuropathy associated with
      anti-MAG/SGGL antibodies, cats were immunized with sulfoglucuronyl paragloboside
      (SGPG). All four cats immunized with SGPG developed clinical signs of sensory
      neuronopathy within 11 months after initial immunization, characterized by
      unsteadiness, falling, hind limb weakness and ataxia. In two cats the ataxia and
      hind limb paralysis were so severe that the animals had to be euthanized.
      Pathological examination revealed sensory ganglionitis with inflammatory
      infiltrates in the dorsal root ganglia. No overt signs of pathology were noted in
      the examined roots or nerves. High titer anti-SGPG/MAG antibodies were detected
      in all 4 cats immunized with SGPG but not in 3 control cats. Our data demonstrate
      that immunization of cats with SGPG induced anti-SGPG antibodies and sensory
      neuronopathy clinically resembling the sensory ataxia of patients with monoclonal
      IgM anti-MAG/SGPG antibodies. This study suggests that these anti-MAG/SGPG
      antibodies play a role in the pathogenesis of this neuropathy.

PMID- 18037503
TI  - Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant
      to multiple sclerosis.
AB  - Cannabinoids may exhibit symptom control in multiple sclerosis (MS). We show here
      that cannabinoid receptor (CBR) agonists can also be immunosuppressive and
      neuroprotective in models of MS. Immunosuppression was associated with reduced:
      myelin-specific T cell responses; central nervous system infiltration and reduced
      clinical disease. This was found to be largely CB(1)R-dependent and only occurred
      at doses that induced significant cannabimimetic effects that would not be
      achieved clinically. Lower, non-immunosuppressive doses of cannabinoids however,
      slowed the accumulation of nerve loss and disability, despite failing to inhibit
      relapses. This further highlights the neuroprotective potential of cannabinoids
      to slow the progression of MS.

PMID- 18037504
TI  - Ingested (oral) alpha-MSH inhibits acute EAE.
AB  - Ingested type I IFN and SIRS peptide administered orally inhibit EAE. We examined
      whether another immunoactive protein, tridecapeptide alpha-MSH, would have
      similar anti-inflammatory effects in EAE after oral administration. B6 mice were
      immunized with MOG peptide 35-55 and gavaged with 0.1 ml of control saline or
      alpha-MSH peptide starting on day -7 preceding active immunization, and
      continuing through day +14 post-immunization. Alpha-MSH peptide delayed disease
      onset and decreased inflammatory foci. CNS lymphocytes showed decreases in Th1
      like encephalitogenic cytokines IL-2 and IL12p70 in the alpha-MSH fed group
      compared to the mock fed group. For Th2-like counter-regulatory cytokines, there
      were increases in peripheral SDF-1 levels comparing alpha-MSH fed vs mock fed
      groups. There were decreases of chemokines MIP-1-alpha and MIP-1-gamma in the CNS
      comparing alpha-MSH fed mice vs mock fed mice. Ingested (orally administered)
      alpha-MSH peptide can reduce clinical disease and inhibit CNS inflammation by
      decreasing migration of antigen driven CNS Th1 cells into the target organ.

PMID- 18037506
TI  - Strain-specific susceptibility for neurodegeneration in a rat model of autoimmune
      optic neuritis.
AB  - Heterogeneity in clinical disease course and histopathology complicates the
      treatment of multiple sclerosis. We detected important differences in
      neurodegeneration in various subtypes of myelin oligodendrocyte glycoprotein
      (MOG)-induced optic neuritis. Dark Agouti (DA) rats showed a significantly higher
      survival of retinal ganglion cells in comparison to Brown Norway rats. After
      surgical transection of the optic nerve neuronal loss was similar in both rat
      strains. We identified an increased expression of interleukin 1beta and glial
      cell line-derived neurotrophic factor in DA rats as the possible mechanism of the
      observed endogenous neuroprotection in MOG-induced optic neuritis.

PMID- 18037505
TI  - Experimental coronavirus retinopathy (ECOR): retinal degeneration susceptible
      mice have an augmented interferon and chemokine (CXCL9, CXCL10) response early
      after virus infection.
AB  - Mouse hepatitis virus induces a biphasic disease in BALB/c mice that consists of
      an acute retinitis followed by progression to a chronic retinal degeneration with
      autoimmune reactivity. Retinal degeneration resistant CD-1 mice do not develop
      the late phase. What host factors contribute to the distinct responses to the
      virus are unknown. Herein, we show that IFN-alpha, IFN-beta and IFN-gamma act in
      concert as part of the innate immune response to the retinal infection. At day 2,
      high serum levels of IFN-gamma, CXCL9 and CXCL10, were detected in BALB/c mice.
      Moreover, elevated levels of CXCL9 and CXCL10 gene expression were detected in
      retinal tissue. Although IFN-gamma and the chemokines were detected in CD-1 mice,
      they were at significantly lower levels compared to BALB/c mice. These augmented
      innate responses observed correlated with the development of autoimmune
      reactivity and retinal degeneration and thus may contribute to the pathogenic
      processes.

PMID- 18037507
TI  - Male--female differences in the impact of beta-adrenoceptor stimulation on
      resistance to experimental metastasis: exploring the effects of age and gonadal
      hormone involvement.
AB  - We studied the development of sexual dimorphism in resistance to NK-sensitive
      experimental metastasis under baseline conditions and following adrenoceptor
      stimulation. With increasing age, baseline resistance to MADB106 lung tumor
      retention (LTR) increased in both sexes, but also the susceptibility to the tumor
      enhancing effects of a beta-adrenergic agonist, metaproterenol. Beginning at 13
      weeks, males exhibited a 2- to 3-fold greater increase in LTR than females
      following adrenoceptor stimulation. This adult dimorphism was robust to
      ovariectomy, and questionably related to androgens. The findings are consistent
      with reduced female responsiveness to sympathetic activation, and substantiate
      the importance of including both sexes when studying neuroimmunomodulation.

PMID- 18037509
TI  - Inhibition of red seabream iridovirus (RSIV) replication by small interfering RNA
      (siRNA) in a cell culture system.
AB  - Small interfering RNAs (siRNAs), mediators of a process of sequence-specific gene
      silencing called RNA interference, have been shown to have activity against a
      wide range of viruses and are considered to be potential antiviral tools. Here,
      we describe an antiviral activity of a siRNA that targets the major capsid
      protein (MCP) gene of red seabream iridovirus (RSIV), a marine fish-pathogenic
      virus, in a cell culture system. Inhibition of RSIV replication was demonstrated
      by reduced MCP expression level and reduced RSIV titer. MCP-targeted siRNA (siR
      MCP) dose-dependently inhibited the expression of MCP gene in cells that either
      transiently expressed or stably expressed the MCP gene. At 84 and 96h after viral
      infection, siR-MCP reduced the expression of MCP gene by 55.2% and 97.1%,
      respectively. Transfection with siR-MCP reduced the production of RSIV particles
      in supernatants of samples infected with RSIV, while the corresponding mismatched
      siR-MCP (MsiR-MCP) and nsRNA controls did not exhibit this effect. These results
      show that MCP-targeted siRNA can effectively and specifically inhibit the
      expression of the target gene and hinder RSIV replication during an in vitro
      infection, providing a potential approach for the control of viral diseases in
      aquaculture.

PMID- 18037508
TI  - Cysteine cathepsin proteases as pharmacological targets in cancer.
AB  - Proteolytic activity is required for several key pro-tumorigenic processes:
      angiogenesis, invasion and metastasis. Consequently, increases in protease
      expression and activity are frequently reported in human cancers, and correlate
      with malignant progression and poor patient prognosis. Cysteine cathepsin
      proteases have recently emerged as an important class of proteolytic enzymes in
      cancer development, and cysteine cathepsin inhibitors have been proposed as
      anticancer agents. In this review, we highlight recent studies that now allow us
      to evaluate critically whether cysteine cathepsin inhibition represents a viable
      therapeutic strategy for the treatment of cancer.

PMID- 18037510
TI  - Poor elemental food quality reduces the toxicity of fluoxetine on Daphnia magna.
AB  - Most chemical contaminants released into the aquatic environment have been tested
      for their toxicity to aquatic organisms using standardized test protocols. The
      extent that results from such toxicity tests vary with the quality of food
      provided to the test organism remains largely unknown. Here, we determined
      whether the elemental food quality consumed by a common test organism, Daphnia
      magna, affects the toxicity of a pharmaceutical, fluoxetine. We found strong
      interactive effects of food quality and fluoxetine on daphnid survival, growth,
      and reproduction. Specifically, we found that D. magna fed phosphorus (P)- and
      nitrogen (N)-rich algal food experienced greater toxicity due to fluoxetine. For
      example, the 6-day LC(50) values for fluoxetine decreased from 0.33 to 0.15 mg L(
      1) when food C:P ratios were increased from 100 to 800. One explanation for this
      result is that fluoxetine, as a selective serotonin reuptake inhibitor, increases
      the activity of serotonin, whose production is linked to growth metabolism in D.
      magna. A regulatory role of serotonin for D. magna's growth and reproduction
      would be consistent with its mitogenic roles in other organisms, although this
      possibility would require further study. Nevertheless, these results demonstrate
      the need to consider elemental food quality in ecotoxicological testing protocols
      that are aimed at evaluating the risks of exposure to chemicals in the aquatic
      environment.

PMID- 18037511
TI  - Characteristics of clock drawing test (CDT) errors by the dementia type:
      quantitative and qualitative analyses.
AB  - We wanted to define the characteristics of errors on the clock drawing test (CDT)
      and we also wanted to determine their value for making the early diagnosis of
      dementia, so the performance of patients with three types of dementia on the four
      CDT was evaluated. The patients with subcortical vascular dementia (VaD) and
      patients with Parkinson's disease with dementia (PDD) had more stimulus bound
      responses. Patients with Alzheimer disease (AD) made significantly more
      conceptual deficit (CD) errors. The CD correlated with the severity of dementia
      and it could be detected in the early and mild stage of dementia. Qualitative and
      quantitative analyses of the errors on the CDT might be useful for making the
      early differential diagnosis of dementia types.

PMID- 18037512
TI  - Safety and feasibility of day case patent foramen ovale (PFO) closure facilitated
      by intracardiac echocardiography.
AB  - Ultrasound guided patent foramen ovale (PFO) closure has traditionally utilized
      transoesophageal echocardiography (TOE) under general anaesthesia. Some centres
      use fluoroscopic guidance alone to facilitate day case PFO closure. Intracardiac
      echocardiography (ICE) is performed via femoral vein access using an 11 Fr sheath
      providing accurate guidance without the necessity for general anaesthesia. The
      safety and feasibility of PFO closure using ICE guidance as a day case procedure
      have not been documented. We present a consecutive series of patients undergoing
      planned day case PFO closure under ICE guidance with transthoracic echocardiogram
      (TTE) follow up. Patients excluded from day case PFO closure were those with
      early pregnancy or unfavourable social circumstances. 53 consecutive adult
      patients (44.2+/-11.0 years; 24 males) were planned for day case PFO closure
      facilitated by ICE. Referral indications were stroke or TIA (n=39), peripheral
      embolism (n=6), decompression sickness (n=7) and severe migraine (n=1). All 53
      patients underwent ICE, with 9/53 (17%) having an atrial septal aneurysm. In 5
      patients no PFO was found. In the remaining 48 patients, PFO closure was achieved
      using the HELEX occluder (n=47) or the Amplatzer device (n=1). Mean procedure and
      fluoroscopy times were 31.0+/-12.4 and 5.3+/-3.9 min respectively. One patient
      failed same day discharge due to groin haematoma. There were no other
      complications. At 3 month follow up, 45/48 (94%) had no residual shunt, with 3
      patients having small residual shunts on colour flow Doppler. In conclusion,
      percutaneous PFO closure as a day case procedure is safe and feasible when
      facilitated by ICE.

PMID- 18037513
TI  - Cardiogenic shock: basics and clinical considerations.
AB  - Cardiogenic shock is a state of tissue hypoperfusion induced by heart failure
      after correction of preload. There are no clear numerical cutoffs to define of
      the hemodynamic parameters of cardiogenic shock but it is usually characterized
      by low blood pressure (systolic blood pressure <90 mmHg or a drop in mean blood
      pressure >30 mmHg, both with a heart rate >60 bpm) with low urine output (<0.5
      ml/kg/h), with or without evidence of organ congestion. Acute myocardial
      infarction is the most common cause. Mortality is high but intra-aortic balloon
      counterpulsation and early coronary interventions have improved the outcome.
      Activation of inflammatory response resulting in expression of inducible nitric
      oxide synthase, activation of inflammatory cytokines, and activation of
      complement system appear to play an important role in the pathogenesis and
      outcome of cardiogenic shock. Nitric oxide synthase inhibitors and C5 complement
      inhibitors are being investigated as potentially useful agents for the treatment
      of cardiogenic shock. Historical perspective, epidemiology, etiology,
      pathophysiology, risk predictors, and management of cardiogenic shock are
      described in this review.

PMID- 18037515
TI  - Ginger (Zingiber officinale Roscoe): a hot remedy for cardiovascular disease?
AB  - Ginger is now exciting considerable interest for its potential to treat many
      aspects of cardiovascular disease. This letter reviews the more recent trials,
      which suggest that ginger shows considerable anti-inflammatory, antioxidant, anti
      platelet, hypotensive and hypolipidemic effect in in vitro and animal studies.
      Human trials have been few and generally used a low dose with inconclusive
      results, however dosages of 5 g or more demonstrated significant anti-platelet
      activity. More human trials are needed using an appropriate dosage of a
      standardised extract. Should these prove positive, ginger has the potential to
      offer not only a cheaper natural alternative to conventional agents but one with
      significantly lower side effects.

PMID- 18037514
TI  - Cardiac rhabdomyoma in tuberous sclerosis: hyperactive Erk signaling.
AB  - Tuberous sclerosis (TS) is a neurological disorder associated with the formation
      of tumors in several organs. Cardiac rhabdomyomas are possibly the earliest
      symptom of TS. Although rhabdomyomas are present in about half of TS patients,
      little is known of their molecular background since these tumors are rarely
      resected. Here we present a patient diagnosed with TS, in whom rhabdomyoma has
      been excised due to deterioration of hemodynamics. We found, that the tumor
      remained heterozygous for the affected TSC2 gene. To analyze molecular mechanisms
      implicated in rhabdomyoma growth, we determined the status of mTOR, Akt and Erk
      pathways. We found that Akt was not upregulated, while mTOR, Erk and its
      substrates were hyperactive. Classic activator of Erk, MEK, was only modestly
      active. We hypothesize that rhabdomyoma arising in TS may progress due to Erk
      potentiation.

PMID- 18037517
TI  - Fish oil curtails the human action potential dome in a heterogeneous manner:
      implication for arrhythmogenesis.
AB  - Omega-3 polyunsaturated fatty acids (omega 3-PUFAs) from fish oil modulate
      various ion channels, including the L-type calcium current (I(Ca,L)). As a
      result, fish oil shortens the cardiac action potential and may cause a loss of
      the dome of the action potential (AP). Under conditions of increased preexisting
      heterogeneity in repolarization this may aggravate dispersion in action potential
      duration. We isolated ventricular myocytes of explanted hearts from patients with
      cardiomyopathy at the time of cardiac transplantation, and characterized spike
      and-dome morphology in the presence of acutely administered fish oil. Fish oil
      omega 3-PUFA eicosapentaenoic acid (EPA), but not the control omega 9-PUFA oleic
      acid (OA), curtails the AP-dome in a heterogeneous manner and may even result in
      loss of the AP-dome in some but not all myocytes.

PMID- 18037518
TI  - Enzyme activation for organic solvents made easy.
AB  - Enzymes are highly selective catalysts that perform intricate chemistries at
      ambient temperatures and pressures. Although water is the solvent of life, it is
      a poor solvent for most synthetic organic reactions and, therefore, most chemists
      avoid aqueous solutions for synthetic applications. However, when removed from
      the aqueous environment and placed in an organic solvent, enzyme activity is
      reduced greatly. Here, we present a general overview of recent efforts to
      activate enzymes for use in nonaqueous media, giving particular focus to the use
      of simple salts as additives that result in significant biocatalytic
      improvements.

PMID- 18037519
TI  - MOSFET detectors in quality assurance of tomotherapy treatments.
AB  - BACKGROUND AND PURPOSE: The purpose of this work was to characterize metal oxide
      semiconductor field-effect transistors (MOSFETs) in a 6 MV conventional linac and
      investigate their use for quality assurance of radiotherapy treatments with a
      tomotherapy Hi-Art unit. MATERIALS AND METHODS: High sensitivity and standard
      sensitivity MOSFETs were first calibrated and then tested for reproducibility,
      field size dependence, and accuracy of measuring surface dose in a 6 MV beam as
      well as in a tomotherapy Hi-Art unit. In vivo measurements were performed on both
      a RANDO phantom and several head and neck cancer patients treated with
      tomotherapy and compared to TLD measurements and treatment plan doses to evaluate
      the performance of MOSFETs in a high gradient radiation field. RESULTS: The
      average calibration factor found was 0.345+/-2.5%cGy/mV for the high sensitivity
      MOSFETs tested and 0.901+/-2.4%cGy/mV for the standard sensitivity MOSFETs.
      MOSFET measured surface doses had an average agreement with ion chamber
      measurements of 1.55% for the high sensitivity MOSFET and 5.23% for the standard
      sensitivity MOSFET when averaged over all trials and field sizes tested. No
      significant dependence on field size was found for the standard sensitivity
      MOSFETs, however a maximum difference of 5.34% was found for the high sensitivity
      MOSFET calibration factors in the field sizes tested. Measurements made with
      MOSFETS on head and neck patients treated on a tomotherapy Hi-Art unit had an
      average agreement of (3.26+/-0.03)% with TLD measurements, however the average of
      the absolute difference between the MOSFET measurements and the treatment plan
      skin doses was (12.2+/-7.5)%. The MOSFET measured patient skin doses also had
      good reproducibility, with inter-fraction deviations ranging from 1.4% to 6.6%.
      Similar results were found from trials using a RANDO phantom. CONCLUSIONS: The
      MOSFETs performed well when used in the tomotherapy Hi-Art unit and did not
      increase the overall treatment set-up time when used for patient measurements. It
      was found that MOSFETs are suitable detectors for surface dose measurements in
      both conventional beam and tomotherapy treatments and they can provide valuable
      skin dose information in areas where the treatment planning system may not be
      accurate.

PMID- 18037520
TI  - Feasibility of adequate dose coverage in permanent prostate brachytherapy using
      divergent needle insertion methods.
AB  - BACKGROUND AND PURPOSE: The purpose of this study is to investigate the
      feasibility of adequate dose coverage in permanent prostate brachytherapy using
      divergent needle insertion methods. These methods can be useful in magnetic
      resonance imaging (MRI) guided needle insertion techniques to avoid pubic arch
      interference. METHODS AND MATERIALS: MRI data were collected from 10 patients
      with T1-T2 prostate cancer. An inverse planning algorithm based on simulated
      annealing was used to optimize the dose distribution for three needle insertion
      methods: divergent needles with a single rotation point, divergent needles with a
      double rotation point, and current parallel needle insertion method. The dose
      constraints were based on our clinical criteria and the recent ESTRO/EAU/EORTC
      recommendations. RESULTS: If the planning target volume (PTV) surrounded the
      prostate and only intraprostatic seeds were allowed, the mean PTV volume that
      received 100% of the prescribed dose (V(100)) was 99% for all needle insertion
      methods. If the PTV was increased to the prostate with a 3mm margin, the mean PTV
      V(100) equalled 94%, 95%, and 94% for the single rotation point, double rotation
      point and current parallel needle insertion method, respectively. If in the
      latter case the tips of the seeds were placed 3mm outside the apex and base of
      the prostate, the mean PTV V(100) was 96% for all needle insertion methods.
      CONCLUSION: This planning study shows that it is feasible to generate an adequate
      dose coverage using divergent needle insertion methods.

PMID- 18037521
TI  - Activation of protein kinase Cepsilon stimulates DNA-repair via epidermal growth
      factor receptor nuclear accumulation.
AB  - PURPOSE: To elucidate the interaction between radioprotector O-phospho-l-tyrosine
      (P-Tyr) with epidermal growth factor receptor (EGFR). METHODS: Molecular effects
      of P-Tyr at the level of EGFR responses were investigated in vitro with TP53
      wildtype bronchial carcinoma cell line A549, which is radio-protected by P-Tyr
      treatment. Nuclear EGFR accumulation was followed by confocal microscopy and
      Western blotting. PKCepsilon protein expression was impaired by specific siRNA.
      Residual DNA-damage was quantified with gammaH(2)AX foci analysis. RESULTS: P-Tyr
      mediated radio-protection was associated with nuclear EGFR accumulation.
      Radiation-induced nuclear EGFR presented increased phosphorylation at residue No.
      T654. We identified PKCepsilon as responsible for T654-phosphorylation. Knockdown
      of PKCepsilon by siRNA blocked both radiation- and P-Tyr-triggered nuclear EGFR
      accumulation. Furthermore, nuclear accumulation of EGFR was associated with
      increased phosphorylation of DNA-dependent protein kinase (DNA-PK) at residue No.
      T2609, essential for DNA-repair. Consequently P-Tyr mediated effects upon DNA-PK
      resulted in a significant reduction of radiation-induced residual gammaH(2)AX
      foci. Knockdown of PKCepsilon increased radiation-induced residual damage and
      abolished the P-Tyr associated radioprotection. In addition, P-Tyr mediated
      radioprotection was completely absent in colony formation assay. CONCLUSION: The
      data presented herein suggest that P-Tyr-treatment mediates activation of
      PKCepsilon, which triggers nuclear EGFR accumulation. Nuclear EGFR is involved in
      phosphorylation of DNA-PK at Thr2609, which has a significant impact upon DNA-DSB
      repair.

PMID- 18037522
TI  - TomoTherapy: implications on daily workload and scheduling patients.
AB  - PURPOSE: The aim of the study was to measure the mean duration of treatments and
      to investigate the occasional events, with extreme influence on treatment time.
      PATIENTS AND METHODS: Time measurements were performed from the start of patient
      treatments (n=72) and one year later (n=27) on TomoTherapy. The time interval of
      the different procedures during treatment was measured. The cause of extra long
      treatment time was examined. All patients received a MV-CT scan prior to
      treatment. RESULTS: The mean overall total treatment time per localization ranged
      from 21.3 to 27.4 min. In 4.1% of the total population extreme long time
      measurements have been observed, interruptions due to equipment malfunction being
      the main cause (57.5%). Comparison between time measurements performed after
      clinical implementation and time measurements performed one year later to examine
      the learning curve, showed no differences. CONCLUSION: Treating a patient on
      TomoTherapy takes approximately 25 min, yielding 19 patients to be treated within
      8 h. However, occasional treatment interruptions and variations in time of
      irradiation have a certain impact on daily patient scheduling for treatment, and
      influences the workload from day-to-day.

PMID- 18037523
TI  - FDG-PET, CT, MRI for diagnosis of local residual or recurrent nasopharyngeal
      carcinoma, which one is the best? A systematic review.
AB  - PURPOSE: To perform a systematic review to compare FDG-PET, CT, and MRI imaging
      for diagnosis of local residual or recurrent nasopharyngeal carcinoma. MATERIALS
      AND METHODS: MEDLINE, EMBASE, the CBMdisc databases and some other databases were
      searched for relevant original articles published from January 1990 to June 2007.
      Inclusion criteria were as follows: Articles were reported in English or Chinese;
      FDG-PET, CT, or MRI was used to detect local residual or recurrent nasopharyngeal
      carcinoma; histopathologic analysis and/or close clinical and imaging follow-up
      for at least 6 months were the reference standard. Two reviewers independently
      extracted data. A software called "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: Twenty-one
      articles fulfilled all inclusion criteria. The pooled sensitivity estimates for
      PET (95%) were significantly higher than CT (76%) (P<0.001) and MRI (78%)
      (P<0.001). The pooled specificity estimates for PET (90%) were significantly
      higher than CT (59%) (P<0.001) and MRI (76%) (P<0.001). The pooled DOR estimates
      for PET (96.51) were significantly higher than CT (7.01) (P<0.001) and MRI (8.68)
      (P<0.001). SROC curve for FDG-PET showed better diagnostic accuracy than CT and
      MRI. The Q* index for PET (0.92) was significantly higher than CT (0.72)
      (P<0.001) and MRI (0.76) (P<0.01). For PET, the sensitivity and diagnostic OR for
      using qualitative analysis were significantly higher than using both qualitative
      and quantitative analyses (P<0.01). For CT, the sensitivity, specificity,
      diagnostic OR, and the Q* index for dual-section helical and multi-section
      helical were all significantly higher than nonhelical and single-section helical
      (P<0.01). And the sensitivity for 'section thickness <5 mm' was significantly
      lower than ' =5 mm' (P<0.01), while the specificity was significantly higher
      (P<0.01). For MRI, there were no significant differences found between magnetic
      field strength <1.5 and > or =1.5 T (P>0.05). CONCLUSION: FDG-PET was the best
      modality for diagnosis of local residual or recurrent nasopharyngeal carcinoma.
      The type of analysis for PET imaging and the section thickness for CT would
      affect the diagnostic results. Dual-section helical and multi-section helical CT
      were better than nonhelical and single-section helical CT.

PMID- 18037524
TI  - Potential of dose optimisation in MRI-based PDR brachytherapy of cervix
      carcinoma.
AB  - BACKGROUND AND PURPOSE: In this study on PDR treatment planning of utero-vaginal
      carcinoma, we analysed the dosimetry of traditional X-ray based plans as it
      presents on MR images. The potential gain of MRI-based dose optimisation was
      assessed. PATIENTS AND METHODS: Sixteen patients boosted with PDR brachytherapy
      after external beam therapy were included. The clinical X-ray based plans were
      projected on MR images. The GTV, HR-CTV and IR-CTV were retrospectively
      contoured, as well as the bladder, rectum and sigmoid colon. The dose in the
      critical organs and target coverage was investigated. In a second phase, the
      plans were manually optimised using the MR information. The objectives were to
      lower the dose in the critical organs (<or= 85 Gy(alphabeta3) for bladder, <or=
      75 Gy(alphabeta3) for rectum and sigmoid colon) and to increase the HR-CTV dose
      to D90 >or= 85 Gy(alphabeta10). RESULTS: In the X-ray based plans, D(2cc) in
      bladder and sigmoid colon exceeded the tolerance doses in 10/16 and 7/16
      patients, respectively. Coverage of the IR-CTV with the 60 Gy(alphabeta10) was
      acceptable. D90 of the HR-CTV was below 85 Gy(alphabeta10) in 13 out of 16
      patients. After optimisation, the dose constraints in the OAR were not exceeded
      anymore in any patient. The average D(2cc) dose reduction was 7+/-6
      Gy(alphabeta3) in the bladder and 7+/-4 Gy(alphabeta3) in the sigmoid colon for
      those patients in which the dose constraint was initially exceeded. In addition,
      an average dose increase of 3 Gy(alphabeta10) was accomplished in the HR-CTV.
      CONCLUSIONS: MRI-based dose optimisation can play an important role to reduce the
      dose delivered to the critical organs and to improve target coverage.

PMID- 18037525
TI  - Quantitative risk assessment of thermophilic Campylobacter spp. and cross
      contamination during handling of raw broiler chickens evaluating strategies at
      the producer level to reduce human campylobacteriosis in Sweden.
AB  - Campylobacter is a major bacterial cause of infectious diarrheal illness in
      Sweden and in many other countries. Handling and consumption of chicken has been
      identified as important risk factors. The purpose of the present study was to use
      data from a national baseline study of thermophilic Campylobacter spp. in raw
      Swedish broiler chickens in order to evaluate some risk management strategies and
      the frequency of consumer mishandling, i.e., handling leading to possible cross
      contamination. A probabilistic model describing variability but not uncertainty
      was developed in Excel and @Risk. The output of the model was the probability of
      illness per handling if the chicken was mishandled. Uncertainty was evaluated by
      performing repeated simulations and substituting model parameters, distributions
      and software (Analytica). The effect of uncertainty was within a factor of 3.2
      compared to the baseline scenario. For Campylobacter spp. prevalence but not
      concentration, there was a one-to-one relation with risk. The effect of a 100
      fold reduction in the levels of Campylobacter spp. on raw chicken reduced the
      risk by a factor of 12 (fresh chicken) to 30 (frozen chicken). Highly
      contaminated carcasses contributed most to risk and it was estimated that by
      limiting the contamination to less than 4 log CFU per carcass, the risk would be
      reduced to less than 17% of the baseline scenario. Diverting all positive flocks
      to freezing was estimated to result in 43% as many cases as the baseline. The
      second best diversion option (54% of baseline cases) was to direct all chickens
      from the two worst groups of producers, in terms of percentages of positive
      flocks delivered, to freezing. The improvement of using diverting was estimated
      to correspond to between 5 to 767 fewer reported cases for the different
      strategies depending on the assumptions of the proportion of reported cases (1 to
      50%) caused by Campylobacter spp. from Swedish chicken. The estimated proportion
      of consumer mishandlings sufficient to explain 1 to 50% of the reported
      campylobacteriosis cases was 0.005-0.25%, or taking estimated underreporting into
      consideration, was 0.05-2.6%. The strategy of using a diversion treatment, e.g.,
      freezing, based on the past performance of producers was promising, but needs to
      be evaluated further. Although challenging, consumer education has a great
      potential given the direct relation between behaviour and risk. However, any
      improvements following implementation of these strategies may be hard to detect
      if less than 50% of reported cases are exposed via chicken and the cross
      contamination route.

PMID- 18037526
TI  - Delivery of proteins and nucleic acids using a non-covalent peptide-based
      strategy.
AB  - The recent discovery of new potent therapeutic molecules which do not reach the
      clinic due to poor delivery and low bioavailability have made of delivery a key
      stone in therapeutic development. Several technologies have been designed to
      improve cellular uptake of therapeutic molecules, including cell-penetrating
      peptides (CPPs), which have been successfully applied for in vivo delivery of
      biomolecules and constitute very promising tools. Distinct families of CPPs have
      been described; some require chemical linkage between the drug and the carrier
      for cellular drug internalization while others like Pep-and MPG-families, form
      stable complexes with drugs depending on their chemical nature. Pep and MPG are
      short amphipathic peptides, which form stable nanoparticles with proteins and
      nucleic acids respectively. MPG and Pep based nanoparticles enter cells
      independently of the endosomal pathway and efficiently deliver cargoes in a fully
      biologically active form into a large variety of cell lines as well as in animal
      models. This review will focus on the mechanisms of non-covalent MPG and Pep-1
      strategies and their applications in cultured cells and animal models.

PMID- 18037527
TI  - Cell penetrating peptide conjugates of steric block oligonucleotides.
AB  - Charge neutral steric block oligonucleotide analogues, such as peptide nucleic
      acids (PNA) or phosphorodiamidate morpholino oligomers (PMO), have promising
      biological and pharmacological properties for antisense applications, such as for
      example in mRNA splicing redirection. However, cellular uptake of free oligomers
      is poor and the utility of conjugates of PNA or PMO to cell penetrating peptides
      (CPP), such as Tat or Penetratin, is limited by endosomal sequestration. Two new
      families of arginine-rich CPPs named (R-Ahx-R)(4) AhxB and R(6)Pen allow
      efficient nuclear delivery of splice correcting PNA and PMO at micromolar
      concentrations in the absence of endosomolytic agents. The in vivo efficacy of (R
      Ahx-R)(4) AhxB PMO conjugates has been demonstrated in mouse models of Duchenne
      muscular dystrophy and in various viral infections.

PMID- 18037528
TI  - Homeoproteins as natural Penetratin cargoes with signaling properties.
AB  - Most of this volume is dedicated to a very important and pragmatic issue which is
      to design ways of internalizing active pharmacological compounds into cells. In
      fact, many vectors have now been developed and the improvement in the technology
      can be seen on two main fronts. A first one is the identification of extremely
      efficient cargoes, for example siRNAs, which can enter the cells once attached to
      the vectors. A second one is the development of chemical vectors designed after
      the properties of the peptides and of tags allowing in vivo addressing to
      specific organs, for example the brain, cell types or sub-cellular compartments.
      This chapter is of a different nature, as it is devoted to the physiological
      significance of protein transduction and to the comparative analysis of the
      Penetratin PTD with its parental proteins, the homeoproteins. Although very
      academic, these two issues are of practical interest for the rational design of
      new vectors and the identification of unforeseen pathological mechanisms and
      pharmacological targets.

PMID- 18037529
TI  - Multifunctional envelope-type nano device (MEND) as a non-viral gene delivery
      system.
AB  - In this review, we describe a key role of octaarginine (R8) in developing our new
      concept of "Programmed Packaging", by which we succeeded in creating a
      multifunctional envelope-type nano device (MEND) as a non-viral gene-delivery
      system. This concept can be applied not only to nuclear targeting of plasmid DNA
      (pDNA) but also to cytosolic delivery of functional nucleic acids such as
      oligonucleotides or siRNA. This concept has been extended to other organelles
      such as mitochondria as a foundation for innovative nanomedicine. Finally, we
      discuss the rate-limiting step in gene delivery by comparing non-viral and viral
      gene delivery systems, which clearly indicates the importance of nuclear
      disposition of pDNA for efficient transfection.

PMID- 18037530
TI  - Genetic modification of cells for transplantation.
AB  - Progress in gene therapy has produced promising results that translate
      experimental research into clinical treatment. Gene modification has been
      extensively employed in cell transplantation. The main barrier is an effective
      gene delivery system. Several viral vectors were utilized in end-stage
      differentiated cells. Recently, successful applications were described with
      adenovirus-associated vectors. As an alternative, embryonic stem cell- and stem
      cell-like systems were established for generation of tissue-specified gene
      modified cells. Owing to the feasibility for genetic manipulations and the self
      renewing potency of these cells they can be used in a way enabling large-scale in
      vitro production. This approach offers the establishment of in vitro cell culture
      systems that will deliver sufficient amounts of highly purified, immunoautologous
      cells suitable for application in regenerative medicine. In this review, the
      current technology of gene delivery systems to cells is recapitulated and the
      latest developments for cell transplantation are discussed.

PMID- 18037531
TI  - Commonness, population depletion and conservation biology.
AB  - Species conservation practice, as opposed to principle, generally emphasizes
      species at risk of imminent extinction. This results in priority lists
      principally of those with small populations and/or geographical ranges. However,
      recent work emphasizes the importance of common species to ecosystems. Even
      relatively small proportional declines in their abundance can result in large
      absolute losses of individuals and biomass, occurrences significantly disrupting
      ecosystem structure, function and services. Here, we argue that combined with
      evidence of dramatic declines in once common species, this suggests the need to
      pay more attention to such depletions. Complementing the focus on extinction
      risk, we highlight important implications for conservation, including the need to
      identify, monitor and alleviate significant depletion events.

PMID- 18037532
TI  - Applicability of grid-net detection system for landfill leachate and diesel fuel
      release in the subsurface.
AB  - The grid-net system estimating the electrical conductivity changes was evaluated
      as a potential detection system for the leakage of diesel fuel and landfill
      leachate. Aspects of electrical conductivity changes were varied upon the type of
      contaminant. The electrical conductivity in the homogeneous mixtures of soil and
      landfill leachate linearly increased with the ionic concentration of pore fluid,
      which became more significant at higher volumetric water contents. However, the
      electrical conductivity in soil/diesel fuel mixture decreased with diesel fuel
      content and it was more significant at lower water contents. The electrode
      spacing should be determined by considering the type of contaminant to enhance
      the electrode sensitivity especially when two-electrode sensors are to be used.
      The electrode sensitivity for landfill leachate was constantly maintained
      regardless of the electrode spacings while that for the diesel fuel significantly
      increased at smaller electrode spacings. This is possibly due to the fact that
      the insulating barrier effect of the diesel fuel in non-aqueous phase was less
      predominant at large electrode spacing because electrical current can form the
      round-about paths over the volume with relatively small diesel fuel content. The
      model test results showed that the grid-net detection system can be used to
      monitor the leakage from waste landfill and underground storage tank sites.
      However, for a successful application of the detection system in the field, data
      under various field conditions should be accumulated.

PMID- 18037533
TI  - Two modelling approaches to water-quality simulation in a flooded iron-ore mine
      (Saizerais, Lorraine, France): a semi-distributed chemical reactor model and a
      physically based distributed reactive transport pipe network model.
AB  - The flooding of abandoned mines in the Lorraine Iron Basin (LIB) over the past 25
      years has degraded the quality of the groundwater tapped for drinking water. High
      concentrations of dissolved sulphate have made the water unsuitable for human
      consumption. This problematic issue has led to the development of numerical tools
      to support water-resource management in mining contexts. Here we examine two
      modelling approaches using different numerical tools that we tested on the
      Saizerais flooded iron-ore mine (Lorraine, France). A first approach considers
      the Saizerais Mine as a network of two chemical reactors (NCR). The second
      approach is based on a physically distributed pipe network model (PNM) built with
      EPANET 2 software. This approach considers the mine as a network of pipes defined
      by their geometric and chemical parameters. Each reactor in the NCR model
      includes a detailed chemical model built to simulate quality evolution in the
      flooded mine water. However, in order to obtain a robust PNM, we simplified the
      detailed chemical model into a specific sulphate dissolution-precipitation model
      that is included as sulphate source/sink in both a NCR model and a pipe network
      model. Both the NCR model and the PNM, based on different numerical techniques,
      give good post-calibration agreement between the simulated and measured sulphate
      concentrations in the drinking-water well and overflow drift. The NCR model
      incorporating the detailed chemical model is useful when a detailed chemical
      behaviour at the overflow is needed. The PNM incorporating the simplified
      sulphate dissolution-precipitation model provides better information of the
      physics controlling the effect of flow and low flow zones, and the time of solid
      sulphate removal whereas the NCR model will underestimate clean-up time due to
      the complete mixing assumption. In conclusion, the detailed NCR model will give a
      first assessment of chemical processes at overflow, and in a second time, the PNM
      model will provide more detailed information on flow and chemical behaviour
      (dissolved sulphate concentrations, remaining mass of solid sulphate) in the
      network. Nevertheless, both modelling methods require hydrological and chemical
      parameters (recharge flow rate, outflows, volume of mine voids, mass of solids,
      kinetic constants of the dissolution-precipitation reactions), which are commonly
      not available for a mine and therefore call for calibration data.

PMID- 18037534
TI  - Prospective survey of indoor fungal contamination in hospital during a period of
      building construction.
AB  - An 18-month survey of indoor fungal contamination was conducted in one
      haematology unit during a period of construction work. Air was sampled with a
      portable Air System Impactor and surfaces with contact Sabouraud plates. During
      this survey the mean concentration of viable fungi in air was 4.2 cfu/m(3) and
      that for surfaces was 1.7 cfu/plate. At the beginning of construction work, there
      were increases in airborne fungal spores (from 3.0 to 9.8 cfu/m(3)) in the unit,
      but concentrations did not exceed 10 cfu/m(3) during the 18-month period. The
      most frequently recovered airborne fungi were Penicillium spp. (27-38%),
      Aspergillus spp. (25%) and Bjerkandera adusta, a basidiomycete identified with
      molecular tools (7-12%). Blastomycetes accounted for more than 50% of the fungal
      flora on surfaces. Investigating the impact of a new air-treatment system (mobile
      Plasmair units), there were significant reductions in fungal contamination for
      the Plasmer -treated rooms, and in these rooms we observed the same level of
      fungal load whether construction work was in progress or not.

PMID- 18037535
TI  - Apigenin inhibits the production of NO and PGE2 in microglia and inhibits
      neuronal cell death in a middle cerebral artery occlusion-induced focal ischemia
      mice model.
AB  - Flavonoids have been intensively studied on their pharmacological activities such
      as anti-cancer, anti-oxidant and anti-inflammation. However, little is known
      about their neuroprotective effects. Recent studies suggest that inflammation
      mediated by microglia may play a role in neurodegenerative diseases. In this
      study, we evaluated the anti-inflammatory effect of various flavonoid compounds
      by using BV-2, a murine microglia cell line. Of the compounds that were
      evaluated, apigenin inhibited the production of nitric oxide and prostaglandin
      E(2) by suppressing the expression of inducible nitric oxide synthase and
      cyclooxygenase-2 protein, respectively. Moreover, apigenin suppressed p38 mitogen
      activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) phosphorylation
      without affecting the activity of extracellular signal-regulated kinase (ERK).
      Apigenin was also found to protect neuronal cells from injury in middle cerebral
      artery occlusion.

PMID- 18037536
TI  - Facilitatory effect of glutamate exocytosis from rat cerebrocortical nerve
      terminals by alpha-tocopherol, a major vitamin E component.
AB  - The effect of alpha-tocopherol, the major vitamin E component, on the release of
      endogenous glutamate has been investigated using rat cerebrocortical nerve
      terminals. Results showed that alpha-tocopherol facilitated the Ca2+-dependent
      but not the Ca2+-independent glutamate release evoked by 4-aminopyridine (4AP).
      This release facilitation was insensitive to glutamate transporter inhibitor L
      trans-PDC or DL-TBOA, and blocked by the exocytotic neurotransmitter release
      inhibitor tetanus neurotoxin, indicating that alpha-tocopherol affects
      specifically the physiological exocytotic vesicular release without affecting the
      non-vesicular release. Facilitation of glutamate exocytosis by alpha-tocopherol
      was not due to its increasing synaptosomal excitability, because alpha-tocopherol
      did not alter the 4AP-evoked depolarization of the synaptosomal plasma membrane
      potential. Rather, examination of the effect of alpha-tocopherol on cytoplasmic
      free Ca2+ concentration revealed that the facilitation of glutamate release could
      be attributed to an increase in voltage-dependent Ca2+ influx. Consistent with
      this, the alpha-tocopherol-mediated facilitation of glutamate release was
      significantly reduced in synaptosomes pretreated with omega-CgTX MVIIC, a wide
      spectrum blocker of N- and P/Q-type Ca2+ channels. In addition, alpha-tocopherol
      modulation of glutamate release appeared to involve a protein kinase C (PKC)
      signalling cascade, insofar as pretreatment of synaptosomes with the PKC
      inhibitor GF109203X effectively suppressed the facilitatory effect of alpha
      tocopherol on 4AP- or ionomycin-evoked glutamate release. Furthermore, alpha
      tocopherol increased the phosphorylation of MARCKS, the major presynapic
      substrate for PKC, and this effect was also significantly attenuated by PKC
      inhibition. Together, these results suggest that alpha-tocopherol exerts an
      increase in PKC activation, which subsequently enhances voltage-dependent Ca2+
      influx and vesicular release machinery to cause an increase in evoked glutamate
      release from rat cerebrocortical glutamatergic terminals. This finding might
      provide important information regarding to the action of vitamin E in the central
      nervous system.

PMID- 18037537
TI  - An efficient tool for identifying inhibitors based on 3D-QSAR and docking using
      feature-shape pharmacophore of biologically active conformation--a case study
      with CDK2/cyclinA.
AB  - This study proposes a fast and efficient approach for identifying novel
      inhibitors when the biologically active conformation of an inhibitor is known.
      The present study was carried out with CDK2/CyclinA inhibitors. The co-crystal
      structure of the most active ligand with CDK2/CyclinA was converted into a
      feature-shape query. This query served three purposes (i) alignment of molecules
      to generate 3D-QSAR model, (ii) rigid docking to the active site using GOLD,
      (iii) extracting hits from databases. A statistically valid 3D-QSAR (r(2)=0.867,
      q(2)=0.887) with good external set prediction (r(pred)(2)=0.890) was obtained.
      The docked poses were analyzed based on their interaction with hinge region
      (Glu81-Leu83) of CDK2. A reasonably good consensus score was generated using 11
      scoring functions. The developed model was then successfully used to identify
      potential leads for CDK2/CyclinA inhibitors.

PMID- 18037538
TI  - DHA deficiency and Alzheimer's disease.

PMID- 18037539
TI  - Presence and functioning of scales and stadiometers in paediatric units.

PMID- 18037540
TI  - Acute inflammatory response does not affect erythrocyte concentrations of copper,
      zinc and selenium.
AB  - BACKGROUND & AIMS: Measuring the nutritional status of trace elements in plasma
      is invalidated in the presence of a systemic inflammatory response. We examined
      the potential of erythrocytes to assess copper, zinc and selenium status in such
      situations. METHODS: Venous blood samples were withdrawn pre-operatively and at
      12, 24, 48, 72 and 168 h post-operatively from 11 patients (6 males and 5
      females) who were admitted for elective knee arthroplasty. C-reactive protein,
      albumin, copper, zinc, selenium and iron were measured in plasma and
      erythrocytes. RESULTS: Plasma zinc and selenium concentrations fell
      significantly: 95% confidence intervals (CI)=-32% to -44% and -22% to -36%,
      respectively. Copper concentrations fell transiently and then increased
      significantly: CI=12-43%. No significant changes were seen in trace element
      concentrations in erythrocytes expressed either as a ratio of haemoglobin or iron
      concentration. Erythrocyte iron levels correlated significantly with haemoglobin
      (r=0.93). CONCLUSIONS: Plasma concentrations of copper, zinc and selenium are
      unreliable markers of status in patients with an acute inflammatory response.
      Erythrocyte concentrations of these trace elements may provide a more reliable
      measure in long-term studies of patients with a chronic systemic inflammatory
      response. Iron can be used instead of haemoglobin as the denominator when
      expressing erythrocyte concentrations of trace elements.

PMID- 18037541
TI  - An important date in rabies history.
AB  - Rabies is estimated to cause 31,000 human deaths in Asia annually. Several recent
      events, including World Rabies Day have brought this neglected disease to the
      attention of the scientific community, governmental authorities, the media and
      the public. It is hoped that this will result in an increased collaboration
      between veterinary and human health authorities, and an involvement at all levels
      necessary for the control and elimination of rabies in dogs, the main reservoir
      and vector of rabies in Asia. Dog rabies elimination is considered as the most
      cost-effective solution to prevent rabies deaths in humans. Asian countries such
      as India and the Philippines have recently adopted the objective of eliminating
      rabies by 2020. To support World Rabies Day, the Asian Rabies Expert Bureau
      (AREB) had its 4th annual meeting from 5 to 7 September 2007, with the objective
      of debating strategies for lowering the human rabies toll. Human rabies deaths
      can already be prevented by improving the compliance to WHO post-exposure
      prophylaxis recommendations. In addition, in regions with a high incidence of
      canine rabies and where rabies control in dogs is not yet achieved or not
      effective, systematic pre-exposure vaccination of children who are the main
      victims of rabies, may prevent their premature deaths.

PMID- 18037542
TI  - All that palsies is not Bell's -the need to define Bell's palsy as an adverse
      event following immunization.
AB  - Bell's palsy has been reported as an adverse event following immunization (AEFI).
      Review of the published literature reveals that several characteristics have been
      used to describe Bell's palsy, which differ significantly from author to author.
      Evidently, the definition of "Bell's palsy" remains controversial, and consensus
      between different medical subspecialties is urgently needed. The Brighton
      Collaboration has formed an international working group with representatives of
      neurology, otorhinolaryngology, pediatrics, electrophysiology, pharmacology,
      pharmaceutical and biotech industry as well as regulatory agencies to create a
      case definition of Bell's palsy as an AEFI.

PMID- 18037544
TI  - Low dose revaccination induces robust protective anti-HBs antibody response in
      the majority of healthy non-responder neonates.
AB  - A sizeable proportion (1-10%) of healthy adults and to lesser extent neonates
      vaccinated with triple 10 microg hepatitis B (HB) vaccine fail to mount a
      protective antibody response. Revaccination with the same vaccine dose has proved
      to be effective in a significant number of primary non-responders. The influence
      of revaccination with lower vaccine doses however has not been studied adequately
      in non-responder neonates. This study was conducted to evaluate the influence of
      supplementary vaccination with a single low and standard dose of a recombinant
      hepatitis B (HB) vaccine in healthy Iranian non-responder neonates to primary
      vaccination. Iranian neonates unable to respond to primary vaccination with 10, 5
      or 2.5 microg doses of recombinant HB vaccine were revaccinated with a single
      additional dose of the same concentration. Serum anti-HBs antibody titer was
      measured by sandwich ELISA. Administration of a single additional dose induced
      seroprotection (anti-HBs> or =10IU/L) in 10/12 (83%), 10/12 (83%) and 21/24
      (87.5%) of non-responder neonates in 10, 5 and 2.5 microg vaccine recipients with
      geometric mean titers (and 95% confidence limits) of 1358 (258-7142), 401 (79
      2038) and 164 (62-433) IU/L, respectively. The log-transformed antibody titer
      obtained for the 10 microg dose recipients was significantly higher than that of
      the 2.5 microg dose vaccinees (p=0.028). No significant differences in anti-HBs
      titer were observed between other groups of vaccinees. However, the total
      seroprotection rates obtained after administration of four low doses of 2.5 and 5
      microg were significantly higher than that obtained after administration of the
      classical three 10 microg doses (p=0.029 and p=0.006, respectively). The total
      seroprotection rates were similar between all groups of vaccines receiving four
      doses of 2.5, 5 and 10 microg vaccine doses. These results indicate that a
      significant proportion of non-responder neonates can be induced to develop a
      protective anti-HBs response following revaccination with a single low dose
      vaccine. Thus adaptation of four low dose (2.5 or 5 microg) vaccination is
      expected to induce higher seroprotection rate and lower or comparable anti-HBs
      antibody titer in healthy neonates.

PMID- 18037543
TI  - Respiratory syncytial virus (RSV) fusion protein expressed by recombinant Sendai
      virus elicits B-cell and T-cell responses in cotton rats and confers protection
      against RSV subtypes A and B.
AB  - The respiratory syncytial virus (RSV) is a serious pediatric pathogen for which
      there is currently no clinically approved vaccine. This report describes the
      design and testing of a new RSV vaccine construct (rSV-RSV-F), created by the
      recombination of an RSV F sequence with the murine parainfluenza virus-type 1
      (Sendai virus, SV) genome. SV was selected as the vaccine backbone for this
      study, because it has previously been shown to elicit high-magnitude, durable
      immune activities in animal studies and has advanced to human safety trials as a
      xenogenic vaccine for human parainfluenza virus-type 1 (hPIV-1). Cells infected
      with the recombinant SV expressed RSV F protein, but F was not incorporated into
      progeny SV virions. When cotton rats were inoculated with the vaccine, high-titer
      RSV-binding and neutralizing antibodies as well as interferon-gamma-producing T
      cells were induced. Most striking was the protection against intra-nasal RSV
      challenge conferred by the vaccine. The rSV-RSV-F construct was also tested as a
      mixture with a second SV construct expressing the RSV G protein, but no clear
      advantage was demonstrated by combining the two vaccines. As a final analysis,
      the efficacy of the rSV-RSV-F vaccine was tested against an array of RSV
      isolates. Results showed that neutralizing and protective responses were
      effective against RSV isolates of both A and B subtypes. Together, experimental
      results encourage promotion of this recombinant SV construct as a vaccine
      candidate for the prevention of RSV in humans.

PMID- 18037545
TI  - Genomic differences of Vaccinia virus clones from Dryvax smallpox vaccine: the
      Dryvax-like ACAM2000 and the mouse neurovirulent Clone-3.
AB  - Conventional vaccines used for smallpox eradication were often denoted one or
      another strain of Vaccinia virus (VACV), even though seed virus was sub-cultured
      multifariously, which rendered the virion population genetically heterogeneous.
      ACAM2000 cell culture vaccine, recently licensed in the U.S., consists of a
      biologically vaccine-like VACV homogeneous-sequence clone from the conventional
      smallpox vaccine Dryvax, which we verified from Dryvax sequence chromatograms is
      genetically heterogeneous. ACAM2000 VACV and CL3, a mouse-neurovirulent clone
      from Dryvax, differ by 572 single nucleotide polymorphisms and 53 insertions
      deletions of varied size, including a 4.5-kbp deletion in ACAM2000 and a 6.2-kbp
      deletion in CL3. The sequence diversity between the two clones precludes
      precisely defining why CL3 is more pathogenic; however, four genes appear
      significantly dissimilar to account for virulence differences. CL3 encodes intact
      immunomodulators interferon-alpha/beta and tumor necrosis factor receptors, which
      are truncated in ACAM2000. CL3 specifies a Cowpox and Variola virus-like ankyrin
      repeat protein that might be associated with proteolysis via ubiquitination. And,
      CL3 shows an elongated thymidylate kinase, similar to the enzyme of the mouse
      neurovirulent VACV-WR, a derivative of the New York City Board of Health vaccine,
      the origin vaccine of Dryvax. Although ACAM2000 encodes most proteins associated
      with immunization protection, the cloning probably delimited the variant epitopes
      and other motifs produced by Dryvax due to its VACV genetic heterogeneity. The
      sequence information for ACAM2000 and CL3 could be significant for resolving the
      dynamics of their different proteomes and thereby aid development of safer, more
      effective vaccines.

PMID- 18037546
TI  - Influence of trunk flexion on hip and knee joint kinematics during a controlled
      drop landing.
AB  - BACKGROUND: An erect posture and greater knee valgus during landing have been
      implicated as anterior cruciate ligament injury risk factors. While previous
      research suggests coupling of knee and hip kinematics, the influence of trunk
      positioning on lower extremity kinematics has yet to be determined. We
      hypothesized that greater trunk flexion during landing would result in greater
      knee and hip flexion and lesser knee valgus. Identification of a modifiable
      factor (e.g. trunk flexion) which positively influences kinematics of multiple
      lower extremity joints would be invaluable for anterior cruciate ligament injury
      prevention efforts. METHODS: Forty healthy individuals completed two drop landing
      tasks while knee, hip, and trunk kinematics were sampled. The first task
      constituted the natural/preferred landing strategy (Preferred), while in the
      second task, subjects actively flexed the trunk upon landing (Flexed). FINDINGS:
      Peak trunk flexion angle was 47 degrees greater for Flexed compared to Preferred
      (P<0.001), and was associated with increases in peak hip flexion angle of 31
      degrees (P<0.001) and peak knee flexion angle of 22 degrees (P<0.001).
      INTERPRETATION: Active trunk flexion during landing produces concomitant
      increases in knee and hip flexion angles. A more flexed/less erect posture during
      landing is associated with a reduced anterior cruciate ligament injury risk. As
      such, incorporating greater trunk flexion as an integral component of anterior
      cruciate ligament injury prevention programs may be warranted.

PMID- 18037547
TI  - Phytoextraction by arsenic hyperaccumulator Pteris vittata L. from six arsenic
      contaminated soils: Repeated harvests and arsenic redistribution.
AB  - This greenhouse experiment evaluated arsenic removal by Pteris vittata and its
      effects on arsenic redistribution in soils. P. vittata grew in six arsenic
      contaminated soils and its fronds were harvested and analyzed for arsenic in
      October, 2003, April, 2004, and October, 2004. The soil arsenic was separated
      into five fractions via sequential extraction. The ferns grew well and took up
      arsenic from all soils. Fern biomass ranged from 24.8 to 33.5 g plant(-1) after 4
      months of growth but was reduced in the subsequent harvests. The frond arsenic
      concentrations ranged from 66 to 6,151 mg kg(-1), 110 to 3,056 mg kg(-1), and 162
      to 2,139 mg kg(-1) from the first, second and third harvest, respectively. P.
      vittata reduced soil arsenic by 6.4-13% after three harvests. Arsenic in the
      soils was primarily associated with amorphous hydrous oxides (40-59%), which
      contributed the most to arsenic taken up by P. vittata (45-72%). It is possible
      to use P. vittata to remediate arsenic-contaminated soils by repeatedly
      harvesting its fronds.

PMID- 18037548
TI  - Effectiveness of aripiprazole in treating obsessive compulsive symptoms.

PMID- 18037549
TI  - Hallucinatory disorder, an original clinical picture? Clinical and imaging data.
AB  - OBJECTIVE: The aim of this study was to verify the existence of areas of clinical
      and neurofunctional homogeneity in a group of patients with auditory verbal
      hallucinations (AVHs) as an isolated symptom, attributable to what we have called
      "Hallucinatory Disorder" (HD) in an attempt to propose a clinical picture that is
      distinct from Schizophrenia. METHOD: Nine patients clinically characterised by
      chronic AVHs were compared with nine schizophrenic patients using the Structured
      Clinical Interview for DSM-III-R, BPRS, PANSS, SAPS, SANS, HRS-A, HRS-D, CDSS,
      MMSE, CGI and PSYRATS. Both groups of patients and nine healthy subjects
      underwent EEG and SPECT examinations. RESULTS: Considering the psychopathological
      dimensions of Schizophrenia, in the HD patients clinical evaluations revealed a
      mono-dimensional clinical profile, whereas all these dimensions contributed to
      the clinical picture of the schizophrenic patients. The SPECT data showed that
      the schizophrenic patients had a reduced rCBF in some areas of the right frontal
      lobe, while the HD patients did not show any area of hypoperfusion. The SPECT
      hyperperfusion data showed an activation pattern in the HD patients that was
      characterised by the involvement of various cortical and subcortical cerebral
      areas, similar to those found in studies of inner speech and auditory verbal
      imagery. CONCLUSIONS: The two groups of patients present significant differences
      that seem capable of supporting the proposed hypothesis that HD may be an
      independent nosographical entity.

PMID- 18037550
TI  - A successful outcome with valproic acid in a case of mania secondary to stroke of
      the right frontal lobe.

PMID- 18037551
TI  - Twenty eight-day dietary toxicity study of Luo Han fruit concentrate in Hsd:SD
      rats.
AB  - A 28-day dietary study was conducted in Hsd:SD rats to evaluate the safety of
      PureLo, a non-caloric powdered concentrate of the Chinese fruit Luo Han Guo,
      which derives its sweetening properties from triterpene glycosides called
      mogrosides. Groups of 20 rats (10/sex/group) were fed diets containing 0, 10,000,
      30,000, or 100,000 ppm PureLo for 28 days (OECD, Redbook 2000). PureLo was well
      tolerated and produced no significant adverse effects. Reduced body weight and
      body weight gain in high-dose animals of both sexes were related to sporadic
      reductions in food consumption; there were no overall differences in feed
      efficiency. Statistically significant changes in clinical chemistry (decreased
      bilirubin, increased total protein) and relative organ weights of liver,
      adrenals, ovaries and/or testes, and epididymides were not correlated with any
      histopathological findings and were not considered adverse. Although a few
      clinical and pathological findings suggest possible treatment-related effects,
      particularly in the high-dose group, these findings were transient, not dose
      dependent, non-adverse, inconsistent, occurred only in one sex, and/or not
      supported by histopathological findings. Under the conditions of this study and
      based on the toxicological endpoints evaluated, the NOAEL for PureLo was 100,000
      ppm in the diet, the highest level tested, equivalent to 7.07 and 7.48 g/kg
      bw/day for male and female rats, respectively.

PMID- 18037552
TI  - On the occurrence of aflatoxin M1 in milk and dairy products.
AB  - Aflatoxins are toxic fungal metabolites found in foods and feeds. When ruminants
      eat AFB(1)-feedstuffs, they metabolise the toxin and excrete AFM(1) in milk. To
      control AFM(1) in foods it is necessary to reduce AFB(1) contamination of feeds
      for dairy cattle by preventing fungal growth and AFB(1) formation in agricultural
      commodities intended for animal use. Corn and corn-based products are one of the
      most contaminated feedstuffs; therefore risk factor analysis of AFB(1)
      contamination in corn is necessary to evaluate risk of AFM(1) contamination in
      milk and milk products. During the corn silage production, the aflatoxins
      production is mostly influenced by: harvest time; fertilization; irrigation; pest
      control; silage moisture; and storage practices. Due to the lower moisture at
      harvest and to the conservation methods, the corn grain is mostly exposed to the
      contamination by Aspergillus species. Therefore, it is necessary to reduce the
      probability of this contaminant through choice of: hybrids; seeding time and
      density; suitable ploughing and fertirrigation; and chemical or biological
      control. Grains harvested with the lowest possible moisture and conservation
      moisture close to or less than 14% are necessary to reduce contamination risks,
      as is maintaining mass to homogeneous moisture. Kernel mechanical damage, grain
      cleaning practices and conservation temperature are also factors which need to be
      carefully controlled.

PMID- 18037554
TI  - Levels of ochratoxin A in serum from urban and rural Portuguese populations and
      estimation of exposure degree.
AB  - Urban and rural population exposure to ochratoxin A (OTA) in central zone of
      Portugal was investigated in three places: Coimbra, Verride and Ereira. The
      analytical method proposed for the determination of ochratoxin A involved
      extraction with chloroform-orthophosphoric acid, cleanup through an
      immunoaffinity column (IAC), high performance liquid chromatography (HPLC) with
      spectrofluorimetric detection (FD) for separation and identification of
      ochratoxin A, and confirmation with HPLC-FD after OTA methylation in serum. The
      limit of quantification of the proposed method was 0.1 microg/L for serum and
      0.05 microg/L for blood. OTA recoveries in serum ranged from 70.3% to 115.3% for
      levels at 0.25 microg/L and 0.5 microg/L, respectively, with a within-day RSD
      between 8.0% and 16.2%. Ochratoxin A serum levels were evaluated in an hundred
      and four donors from Coimbra city, Verride, and Ereira. The study revealed a
      frequency of detection of 100%. The ratio of ochratoxin A level in serum to whole
      blood was 2.0+/-0.7. The overall concentrations range from 0.25 to 2.49 microg/L,
      0.14 to 1.91 microg/L, and 0.19 to 0.96 microg/L, for samples of Verride, Ereira,
      and Coimbra, respectively. The mean concentration and standard deviation were
      0.78+/-0.53 microg/L, 0.44+/-0.31 microg/L, and 0.42+/-0.18 microg/L for the same
      samples. A significant difference was found in Verride population (P
      value=0.000). Levels of OTA are clearly higher in males from rural areas than in
      females. For all samples, a significant difference was found in Verride male
      population (P-value=0.014).

PMID- 18037553
TI  - Effects of antioxidants on cancer prevention and neuromotor performance in Atm
      deficient mice.
AB  - Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by
      immunodeficiency, neurodegeneration and cancer. The disease results from bi
      allelic mutations in the AT mutated (ATM) gene involved in cell cycle checkpoint
      control and repair of DNA double-strand breaks. Evidence has been accumulating
      that oxidative stress is associated with AT and may be involved in the
      pathogenesis of the disease. This led to a hypothesis that antioxidants may
      alleviate the symptoms of AT. Consequently, several studies were conducted in Atm
      deficient mice to examine the role of antioxidants in cancer prevention and/or
      correction of neuromotor performance. N-acetyl-l-cysteine (NAC), EUK-189, tempol,
      and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) have been tested in
      Atm deficient mice. In contrast to other antioxidants, NAC has been used in the
      clinical practice for many decades and is available as a dietary supplement. In
      this article, we review chemoprevention studies in Atm deficient mice and, in
      more detail, our findings on the effect of NAC. Our short-term study showed that
      NAC suppressed genome rearrangements linked to cancer. The long-term study
      demonstrated that NAC reduced the incidence and multiplicity of lymphoma and
      improved some aspects of motor performance.

PMID- 18037555
TI  - The influence of two home-applied bleaching agents on enamel microhardness: an in
      situ study.
AB  - OBJECTIVE: This in situ study evaluated the influence of two home-applied
      bleaching agents (10% carbamide peroxide and 7.5% hydrogen peroxide) on enamel
      microhardness. METHODS: Ninety enamel slabs were obtained from human third molars
      and baseline Knoop hardness measurements were recorded under a 50 g load for 5s.
      The specimens were attached to intra-oral devices delivered to 10 volunteers
      (donor of the teeth) who used the devices 24h/day throughout the experiment. The
      specimens were divided in three groups, two experimental and one control; in the
      last group, enamel slabs were not submitted to bleaching agents, but exposed only
      to the action of saliva. Two custom-made trays were made for each volunteer to
      recover the teeth and the appliances containing the enamel slabs. The bleaching
      regimen was 1h/day for 21 consecutive days. Subsequently, additional hardness
      measurements were recorded. RESULTS: The mean values of the baseline and final
      microhardness were: 348 and 352.2; 346.6 and 354.5; 342 and 340.8, for control,
      10% carbamide peroxide and 7.5% hydrogen peroxide groups, respectively. One-way
      ANOVA of the microhardness mean values revealed no statistically significant
      differences among groups, the specimens treated with 7.5% hydrogen peroxide has
      shown a tendency (p=0.056) to microhardness decrease. CONCLUSIONS: Data suggested
      that the tested home bleaching agents did not change the superficial enamel
      microhardness.

PMID- 18037556
TI  - Investigating the binding of curcumin derivatives to bovine serum albumin.
AB  - The interaction of bovine serum albumin (BSA) with isoxazolcurcumin (IOC) and
      diacetylcurcumin (DAC) has been investigated. Binding constants obtained were
      found to be in the 10(5) M(-1) range. Minor conformational changes of BSA were
      observed from circular dichroism (CD) and Fourier transformed infrared (FT-IR)
      studies on binding. Based on Forster's theory of non-radiation energy transfer,
      the average binding distance, r between the donor (BSA) and acceptors IOC and DAC
      was found to be 3.79 and 4.27 nm respectively. Molecular docking of
      isoxazolcurcumin and diacetylcurcumin with bovine serum albumin indicated that
      they docked close to Trp 213, which is within the hydrophobic subdomain.

PMID- 18037557
TI  - Study on the molecular mechanism of inhibiting HIV-1 integrase by EBR28 peptide
      via molecular modeling approach.
AB  - Human immunodeficiency virus type 1 (HIV-1) integrase (IN) is an essential enzyme
      in the HIV-1 lifecycle which aids the integration of viral DNA into the host
      chromosome. Recently synthesized 12-mer peptide EBR28, which can strongly bind to
      IN, is one of the most potential small peptide leading compounds inhibiting IN
      binding with viral DNA. However, the binding mode between EBR28 peptide with HIV
      1 IN and the inhibition mechanism remain uncertain. In this paper, the binding
      modes of EBR28 with HIV-1 IN monomer core domain (IN(1)) and dimmer core domain
      (IN(2)) were investigated by using molecular docking and molecular dynamics (MD)
      simulation methods. The results indicated that EBR28 bound to the interfaces of
      the IN(1) and IN(2) systems mainly through the hydrophobic interactions with the
      beta3, alpha1 and alpha5 regions of the proteins. The binding free energies for
      IN(1) with a series of EBR28 mutated peptides were calculated with the MM/GBSA
      model, and the correlation between the calculated and experimental binding free
      energies is very good (r=0.88). Thus, the validity of the binding mode of IN(1)
      with EBR28 was confirmed. Based on the binding modes, the inhibition mechanism of
      EBR28 was explored by analyzing the essential dynamics (ED), energy decomposition
      and the mobility of EBR28 in the two docked complexes. The proposed inhibition
      mechanism is represented that EBR28 binds to the interface of IN(1) to form the
      IN(1)_EBR28 complex and preventes the formation of IN dimmer, finally leads to
      the partial loss of binding potency for IN with viral DNA. All of the above
      simulation results agree well with experimental data, which provide us with some
      helpful information for designing anti-HIV small peptide drugs.

PMID- 18037558
TI  - Comparison of contrast-enhanced color Doppler imaging (CDI), computed tomography
      (CT), and magnetic resonance imaging (MRI) for the detection of crossing vessels
      in patients with ureteropelvic junction obstruction (UPJO).
AB  - OBJECTIVE: To assess the use of contrast-enhanced color Doppler imaging (CDI),
      computed tomography (CT), and magnetic resonance imaging (MRI) for the detection
      of crossing vessels at the ureteropelvic junction (UPJ) in patients with
      ureteropelvic junction obstruction (UPJO). MATERIALS AND METHODS: Forty-eight
      patients aged 18-69 yr (mean age, 52) who had been diagnosed with an UPJO on
      intravenous pyelography and diuretic renography were included. Contrast-enhanced
      CDI was performed by using both color Doppler frequency and color Doppler
      amplitude ("Power") modes. Spiral CT was performed by using a three-phase CT
      (arterial, venous, and excretory phases) allowing for CT angiography. MRI
      technique included dual-phase magnetic resonance angiography (arterial, venous)
      for the assessment of respective arteries and veins. The type (ie, arterial or
      venous) and position of the vessel relative to the UPJ (ie, anterior or
      posterior) were assessed. The CDI, CT, and MRI findings were correlated with the
      surgical findings at laparoscopic pyeloplasty. RESULTS: Forty-four of 48 patients
      (92%) demonstrated crossing vessels at subsequent laparoscopy. Altogether a total
      of 60 vessels were detected. Contrast-enhanced CDI and MRI correctly detected all
      crossing vessels (accuracy, 100%), whereas CT missed four posterior crossing
      veins (accuracy, 93%). CONCLUSION: Contrast-enhanced CDI is recommended as first
      line imaging modality for the detection of crossing vessels in patients with
      UPJO.

PMID- 18037559
TI  - Editorial comment on: comparison of contrast-enhanced color Doppler imaging
      (CDI), computerized tomography (CT), and magnetic resonance imaging (MRI) for the
      detection of crossing vessels in patients with ureteropelvic junction obstruction
      (UPJO).

PMID- 18037560
TI  - Editorial comment on: comparison of contrast-enhanced color doppler imaging
      (CDI), computerized tomography (CT), and magnetic resonance imaging (MRI) for the
      detection of crossing vessels in patients with ureteropelvic junction obstruction
      (UPJO).

PMID- 18037561
TI  - The role of somatostatin analogues in the treatment of neuroendocrine tumours.
AB  - Neuroendocrine tumours belong to a heterogeneous family of neoplasms, originating
      in endocrine glands (such as the pituitary, parathyroid or the neuroendocrine
      adrenal glands), in endocrine islets (within the thyroid or pancreas) as well as
      in endocrine cells dispersed between exocrine cells throughout the digestive or
      respiratory tracts. The clinical behaviour of neuroendocrine tumours is variable;
      they may be functioning or not functioning, ranging from well-differentiated slow
      growing neuroendocrine tumours to poorly differentiated neuroendocrine tumours,
      which are highly aggressive malignant tumours. The development of somatostatin
      analogues as important diagnostic and treatment tools have revolutionised the
      clinical management of patients with neuroendocrine tumours. However, although
      symptomatic relief and stabilisation of tumour growth for various periods of time
      are observed in many patients treated with somatostatin analogues, tumour
      regression is rare. Development of new somatostatin analogues and new drug
      combination therapies should further improve the clinical management of these
      patients.

PMID- 18037562
TI  - LIBS-an efficient approach for the determination of Cr in industrial wastewater.
AB  - In the present paper, LIB spectra of different water samples having varying
      concentration of Cr (certified reference material, CRM) have been recorded by
      using liquid jet (fabricated in our laboratory) configuration. Calibration curves
      for different atomic lines of Cr are compared and it is found that calibration
      curve for Cr II (283.5 nm) atomic line is the best in terms of the Limit of
      detection (LOD) which is found to be 30 ppm. This calibration curve has been used
      for quantification of Cr in wastewater collected from Cr-electroplating industry
      where the concentration of Cr is found to be 1500 ppm. Its removal can be planned
      by biological system, which is in progress.

PMID- 18037563
TI  - Study of the sensitivity of the first four flexural modes of an AFM cantilever
      with a sidewall probe.
AB  - The resonant frequency and sensitivity of flexural vibration for an atomic force
      microscope (AFM) cantilever with a sidewall probe have been analyzed. A closed
      form expression for the sensitivity of vibration modes has been obtained using
      the relationship between the resonant frequency and contact stiffness of
      cantilever and sample. The results show that a sidewall scanning AFM is more
      sensitive when the contact stiffness is lower and that the first mode is the most
      sensitive. However, the high-order modes become more sensitive than the low-order
      modes as the contact stiffness increases. The resonance frequency of an AFM
      cantilever is low when contact stiffness is small. However, the frequency rapidly
      increases as contact stiffness increases. In addition, it can be found that the
      effects of the vertical extension on the sensitivity and the resonant frequency
      of an AFM cantilever are significant. Decreasing the length of vertical extension
      can increase the resonance frequency and sensitivity of mode 1 when the contact
      stiffness is small. However, the situation is reverse when the contact stiffness
      becomes large.

PMID- 18037564
TI  - Chemical mapping of the distribution of viruses into infected bacteria with a
      photothermal method.
AB  - We show that an infrared spectromicroscopy method based on a photo-thermal
      effect, is able to localize single viruses as well when they are isolated and
      when they are located inside the bacteria they have infected. In this latter
      case, although the topography performed by an AFM cannot image the viruses, the
      AFMIR is able to do so. In addition, we are able to determine different stages of
      the bacteria infection.

PMID- 18037565
TI  - TEM characterization of Ge precipitates in an Al-1.6at% Ge alloy.
AB  - The growth mechanism and morphology of Ge precipitates in an Al-Ge alloy was
      characterized by a combination of in-situ transmission electron microscopy, high
      resolution transmission electron microscopy and three-dimensional electron
      tomography. Anisotropic growth of rod-shaped Ge precipitates was observed by in
      situ transmission electron microscopy over different time periods, and faceting
      of the precipitates was clearly seen using high-resolution transmission electron
      microscopy and three-dimensional electron tomography. This anisotropic growth of
      rod-shaped Ge precipitates was enhanced by vacancy concentration as proposed
      previously, but also by surface diffusion as observed during the in-situ
      experiment. Furthermore, a variety of precipitate morphologies was identified by
      three-dimensional electron tomography.

PMID- 18037566
TI  - A simple method of cutting meshed split thickness skin grafts to desired size.

PMID- 18037567
TI  - Substances used as first-aid home treatment of burns among young children at
      Milas, Turkey.

PMID- 18037568
TI  - Short- and long-term bacterial inhibiting effect of high concentrations of
      glycerol used in the preservation of skin allografts.
AB  - Human skin allografts are important in the treatment of severe burns.
      Transplantation of skin allografts can cause bacterial transmission. Glycerol in
      higher concentrations is an appropriate storage medium for allograft cadaver skin
      and has been attributed an antimicrobial effect. We investigated this effect in
      more detail. First, the minimal inhibitory concentration of glycerol was
      determined for 13 bacteria and 1 yeast. This gives an indication about an
      immediate (20h of incubation) antibacterial effect of glycerol. Second, effect of
      glycerol in the long-term was studied. Therefore, the survival time was
      determined for 11 different bacteria suspended in different concentrations of
      glycerol (50% and 85%) and incubated at three temperatures (4, 24, and 36 degrees
      C). The minimal inhibitory concentration exceeded 256microg/mL, thus glycerol had
      no direct inhibitory effect. In contrast, a long-term antimicrobial effect was
      present and more pronounced at higher concentrations of glycerol and higher
      temperatures of incubation. The mean survival time of Pseudomonas aeruginosa
      strains in glycerol 85% at 24 degrees C was 2.6 days, 14.7 days for the tested
      staphylococci and 29.6 days for three vegetative Bacillus species. In conclusion,
      microbial safety of glycerol-preserved skin can be increased by preserving skin
      allografts for some weeks at room temperature.

PMID- 18037569
TI  - Lego as a customisable pressure garment insert.

PMID- 18037571
TI  - Childhood attention deficit hyperactivity disorder and the development of
      substance use disorders: valid concern or exaggeration?
AB  - Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder
      associated with many behavioral problems in adolescence and adulthood. In
      particular, researchers have identified comorbid substance use disorders in many
      adolescents and young adults who were diagnosed with ADHD as children.
      Conflicting reports exist regarding the developmental risk for substance use
      problems and disorders in these individuals. This paper reviews the recent
      literature evaluating the relationship between childhood ADHD and substance use.
      Research suggests that in the absence of conduct disorder, ADHD carries only a
      moderate risk for subsequent substance use. Degree of risk appears to be related
      to specific drugs of abuse and particular ADHD symptoms. Additionally, whether
      stimulant treatment of ADHD symptoms predisposes children to later substance use
      is an important concern. Currently, little evidence exists to support this notion
      and most research suggests that stimulant treatment serves as a protective factor
      for substance use. ADHD is an important precursor to subsequent disorders in
      children and further research is necessary to diminish the risk for substance use
      in this population.

PMID- 18037570
TI  - Interleukin-1 receptor type 1-deficient mice fail to develop social stress
      associated glucocorticoid resistance in the spleen.
AB  - Frequent or chronic stress as a result of repeated or persistent exposure to
      social challenges has been shown to affect the glucocorticoid (GC) responsiveness
      of immune cells in mice. Lipopolysaccharide-stimulated splenocytes of mice that
      were repeatedly subjected to social disruption were less sensitive to the anti
      inflammatory actions of GC as evident from an increased production of pro
      inflammatory cytokines and enhanced cell survival. The development of functional
      GC resistance was accompanied by the accumulation of GC-insensitive CD11b(+)
      cells in the spleen. These cells were shown to exhibit impaired nuclear
      translocation of the GC receptor and lack of GC-induced suppression of NF-kappaB.
      Similar impairments in GC receptor function have been reported after in vitro
      treatment of various cell lines with interleukin (IL)-1. The aim of this study
      was to elucidate whether IL-1 is a critical factor for the development of GC
      resistance in socially stressed mice. In the first experiment, we investigated if
      repeated social stress alters plasma levels and tissue gene expression of IL
      1alpha and IL-1beta. It revealed that recurrent stressor exposure significantly
      increased splenic and hepatic mRNA expression and the plasma protein level of IL
      1beta, and hepatic mRNA expression of IL-1alpha. In the second experiment, IL-1
      receptor type 1 (IL1R1)-deficient mice were subjected to the stressor and both
      the tissue distribution of CD11b(+) cells and the GC sensitivity of the
      splenocytes were compared to wildtype mice. Mice lacking the IL1R1 exhibited
      adrenal hypertrophy, thymic involution, and elevated serum corticosterone levels
      in response to the stressor but did not show splenic accumulation of CD11b(+)
      cells and failed to develop GC resistance. These findings suggest that IL-1 plays
      a critical role in the development of the social stress-associated GC resistance
      in the murine spleen.

PMID- 18037572
TI  - The lack of non-steroid isoprenoids causes oxidative stress in patients with
      mevalonic aciduria.
AB  - Mevalonic aciduria belongs to a group of rare inherited metabolic disorders
      related to cholesterol biosynthesis. The pathogenesis of mevalonic aciduria is
      not clear, although the cause is known - a genetic defect leading to a deficiency
      in mevalonate kinase activity. The lack of non-steroid isoprenoids in patients
      with mevalonic aciduria might cause oxidative stress due to a decreased
      production of endogenous antioxidants including ubiquinone 10, selenoproteins and
      glutathione peroxidase. The Moosmann-Behl hypothesis of statin-induced muscular
      and neuronal damage mediated by oxidative stress might explain at least partially
      the pathogenesis of mevalonic aciduria. Studies focusing on the role of oxidative
      stress in patients suffering from disorders in cholesterol biosynthesis are
      needed to support adjuvant antioxidative treatment.

PMID- 18037573
TI  - Basilar artery angulation and vertigo due to the hemodynamic effect of dominant
      vertebral artery.
AB  - Vertebral arteries form the basilar artery at the pontobulbar junction. The
      vertebral artery may have dominancy in one of them. The branches of basilar
      arteries supply blood for the vestibular nuclei and its connections. Vertigo is
      seen generally in the upper middle aged patients. Vertigo can be observed in
      dolichoectasia of basilar artery such as angulation and elongation, because of
      the diminished blood supply and changed hemodynamic factors of vestibular nuclei
      and its connections. We hypothesized that angulation or elongation of basilar
      artery can be estimated according to the unilateral vertebral artery dominant
      hypertensive patients. The basilar artery can angulate from the dominant side of
      vertebral artery to the recessive side. These angulation and elongation can
      effect the hemodynamic factors in absence of growing collateral arteries. So, the
      vertigo attacks may occur in these patients.

PMID- 18037574
TI  - The telescope hypothesis for the etiology of intussusception: surgical narrowing
      of the ileocecal angle as a treatment strategy.

PMID- 18037575
TI  - Thyroid adenomatous nodule with bizarre nuclei: a case report and mutation
      analysis of the p53 gene.
AB  - We present a rare case of adenomatous nodule with bizarre nuclei. The patient was
      incidentally found to have a nodule in the left lobe of the thyroid gland by
      ultrasonographic examination. Papillary thyroid carcinoma was suspected by fine
      needle aspiration cytology, and hemithyroidectomy was performed. The demarcated
      1.5-cm nodule had a multinodular appearance with various features, including
      micro- and macrofollicular components, cystic degeneration, a hyalinized area,
      and a papillary structure. Hyperchromatic bizarre nuclei with cytoplasmic
      inclusions were restrictively observed in the microfollicular area. The bizarre
      nuclei demonstrated diffuse p53 protein immmunoreactivity, but no mutation in
      exons 5-9 of the p53 gene was detected. The bizarre nuclei were reactive for anti
      5-methyl-2'-deoxycytidine antibody, indicating the enclosure of presumably
      inactive methylated DNA. The intranuclear cytoplasmic inclusions (ICIs) were
      proven to contain vimentin and beta-catenin by immunohistochemistry. In this
      case, a degenerative process is involved in the formation of bizarre nuclei
      because of the compression by surrounding micronodules, unidentifiable mitotic
      figures, and a quite low proliferative activity. This case suggests that bizarre
      nuclei and ICIs, which might be identical to those of papillary carcinomas, can
      be seen in benign thyroid lesions, and overdiagnosis should be avoided regardless
      of immunohistochemical overexpression of p53.

PMID- 18037576
TI  - Automated data mining of a proprietary database system for physician quality
      improvement.
AB  - PURPOSE: Physician practice quality improvement is a subject of intense national
      debate. This report describes using a software data acquisition program to mine
      an existing, commonly used proprietary radiation oncology database to assess
      physician performance. METHODS AND MATERIALS: Between 2003 and 2004, a manual
      analysis was performed of electronic portal image (EPI) review records. Custom
      software was recently developed to mine the record-and-verify database and the
      review process of EPI at our institution. In late 2006, a report was developed
      that allowed for immediate review of physician completeness and speed of EPI
      review for any prescribed period. RESULTS: The software extracted >46,000 EPIs
      between 2003 and 2007, providing EPI review status and time to review by each
      physician. Between 2003 and 2007, the department EPI review improved from 77% to
      97% (range, 85.4-100%), with a decrease in the mean time to review from 4.2 days
      to 2.4 days. The initial intervention in 2003 to 2004 was moderately successful
      in changing the EPI review patterns; it was not repeated because of the time
      required to perform it. However, the implementation in 2006 of the automated
      review tool yielded a profound change in practice. Using the software, the
      automated chart review required approximately 1.5 h for mining and extracting the
      data for the 4-year period. CONCLUSION: This study quantified the EPI review
      process as it evolved during a 4-year period at our institution and found that
      automation of data retrieval and review simplified and facilitated physician
      quality improvement.

PMID- 18037577
TI  - Treatment of primary cutaneous CD30+ anaplastic large-cell lymphoma with
      radiation therapy.
AB  - PURPOSE: Primary cutaneous CD30+ anaplastic large-cell lymphoma (CALCL) is a
      relatively rare and indolent variant of cutaneous T-cell lymphoma (CTCL). This
      report examines the response of localized disease to radiation alone. METHODS:
      The Yale Cancer Center records were examined, and all patients with CTCL from
      January 1, 2001, to September 1, 2006, evaluated in the Department of Therapeutic
      Radiology were identified. Only those patients with localized or single CALCL
      lesions, no clinical evidence or history of lymphomatoid papulosis, no history of
      other CTCLs, no history of other skin disorders, lack of lymph node involvement,
      unambiguous pathology reports, and treatment with radiation alone were included.
      RESULTS: Eight patients were identified. Median age was 67 years, and gender was
      split evenly. Patients received radiation ranging from 34 to 44 Gy in 2-Gy
      fractions. Most patients (5 of 8) received 40 Gy, using 6 to 9 MeV electrons with
      0.5 to 2 cm of bolus. All patients had a complete response. All patients were
      without evidence of disease at the most recent follow-up (median follow-up, 12
      months). Radiation therapy was well tolerated, and the only recorded toxicity was
      Grade I to II dermatitis. CONCLUSIONS: Radiation therapy alone for localized
      CALCL is very well tolerated and clinical response is excellent. A dose of 40 Gy
      in 2-Gy fractions seems to be well tolerated and effective in inducing a complete
      response. Lower doses may be effective in achieving the same result, but data are
      not available. Longer follow-up is necessary before conclusions regarding durable
      disease-free survival can be made.

PMID- 18037578
TI  - Prognostic value of baseline lymphocyte count in cervical carcinoma treated with
      concurrent chemoradiation.
AB  - PURPOSE: This study examined factors predicting tumor response and progression
      free survival in patients with locally advanced cervical carcinoma treated with
      concurrent chemoradiation (CCRT). METHODS AND MATERIALS: Medical records of 143
      patients with locally advanced cervical carcinoma (International Federation of
      Gynecology and Obstetrics Stage IB2 to IVA) treated with CCRT were reviewed.
      Univariate and multivariate analyses were used to retrospectively evaluate
      prognostic factors, including baseline lymphocyte count, that affect tumor
      response and progression-free survival. RESULTS: Of the variables evaluated,
      greater baseline lymphocyte count was the factor most predictive of a complete
      clinical response, followed by smaller tumor size (p = 0.003 and p = 0.007,
      respectively). Multivariate analysis showed baseline lymphocyte count, which was
      treated as a continuous variable with every 1 x 10(9) lymphocytes/L, to remain a
      prognostic factor with an odds ratio of 3.08 (95% confidence interval, 1.31
      7.23). In addition, a statistically significant association (p = 0.023) was found
      between baseline lymphocyte count and progression-free survival, with a hazard
      ratio of 0.42 (95% confidence interval, 0.20-0.89) in the Cox proportional
      hazards model. CONCLUSIONS: Despite the small number of patients and possible
      biologic variation existing in lymphocyte subset number and activity, these
      findings highlight the strong prognostic value of baseline lymphocyte count in
      patients with locally advanced cervical carcinoma treated with CCRT. Therefore, a
      larger number of patients and analysis of lymphocyte subsets are needed.

PMID- 18037579
TI  - Variability of four-dimensional computed tomography patient models.
AB  - PURPOSE: To quantify the interfractional variability in lung tumor trajectory and
      mean position during the course of radiation therapy. METHODS AND MATERIALS:
      Repeat four-dimensional (4D) cone-beam computed tomography (CBCT) scans (median,
      nine scans/patient) routinely acquired during the course of treatment were
      analyzed for 56 patients with lung cancer. Tumor motion was assessed by using
      local rigid registration of a region of interest in the 3D planning CT to each
      phase in the 4D CBCT. Displacements of the mean tumor position relative to the
      planned position (baseline variations) were obtained by using time-weighted
      averaging of the motion curve. RESULTS: The tumor trajectory shape was found to
      be stable interfractionally, with mean variability not exceeding 1 mm (1 SD) in
      each direction for the inhale and exhale phases. Interfractional baseline
      variations, however, were large, with 1.6- (left-right), 3.9- (cranial-caudal),
      and 2.8-mm (anterior-posterior) systematic variations (1 SD) and 1.2- (left
      right), 2.4- (cranial-caudal) and 2.2-mm (anterior-posterior) random variations.
      Eliminating baseline variations by using soft-tissue guidance decreases planning
      target volume margins by approximately 50% compared with bony anatomy-driven
      protocols for conventional fractionation schemes. CONCLUSIONS: Systematic and
      random baseline variations constitute a substantial portion of the geometric
      variability present in the treatment of patients with lung cancer and require
      generous safety margins when relying on accurate setup/immobilization or bony
      anatomy-driven correction strategies. The 4D-CBCT has the ability to accurately
      monitor tumor trajectory shape and baseline variations and drive image-guided
      correction strategies that allows safe margin reduction.

PMID- 18037580
TI  - Recurrence in region of spared parotid gland after definitive intensity-modulated
      radiotherapy for head and neck cancer.
AB  - PURPOSE: To discuss the implications of three examples of periparotid recurrence
      after definitive intensity-modulated radiotherapy (IMRT) for head and neck cancer
      (HNC). METHODS AND MATERIALS: We present 3 patients with HNC who underwent
      definitive IMRT with concurrent chemotherapy and later had treatment failure in
      or near a spared parotid gland. Two patients had bilateral multilevel nodal
      disease, and all had Level II nodal disease ipsilateral to the site of
      recurrence. The patients were treated using dose-painting IMRT with a dose of 70
      Gy to the gross tumor volume and 59.4 Gy or 54 Gy to the high-risk or low-risk
      clinical tumor volume, respectively. The parotid glands were spared bilaterally.
      The patients had not undergone any surgical treatment for HNC before
      radiotherapy. RESULTS: All patients had treatment failure in the region of a
      spared parotid gland. Failure in the 2 patients with bilateral multilevel nodal
      involvement occurred in the periparotid lymph nodes. The third patient developed
      a dermal metastasis near the tail of a spared parotid gland. On pretreatment
      imaging, the 2 patients with nodal failure had small nonspecific periparotid
      nodules that showed no hypermetabolic activity on positron emission tomography.
      CONCLUSION: For HNC patients receiving definitive IMRT, nonspecific positron
      emission tomography-negative periparotid nodules on pretreatment imaging should
      raise the index of suspicion for subclinical disease in the presence of
      multilevel or Level II nodal metastases. Additional evaluation of such nodules
      might be indicated before sparing the ipsilateral parotid gland.

PMID- 18037581
TI  - HI-CHART: a phase I/II study on the feasibility of high-dose continuous
      hyperfractionated accelerated radiotherapy in patients with inoperable non-small
      cell lung cancer.
AB  - PURPOSE: To determine the feasibility of high-dose continuous hyperfractionated
      accelerated radiotherapy in patients with inoperable non-small-cell lung cancer
      (NSCLC). PATIENTS AND METHODS: In a prospective, Phase I/II study, according to
      the risk for radiation pneumonitis, three risk groups were defined: V(20) <25%,
      V(20) 25-37%, and V(20) >37%. The dose was administered in three steps from 61.2
      Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38
      fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional
      conformal technique. Only the mediastinal lymph node areas that were positive on
      the pretreatment (18)F-deoxy-D-glucose positron emission tomography scan were
      included in the target volume. The primary endpoint was toxicity. RESULTS: A
      total of 48 Stage I-IIIB patients were included. In all risk groups, 68.40 Gy/38
      fractions/25 days could be administered. Maximal toxicity according to the risk
      groups was as follows: V(20) <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3
      reversible esophageal toxicity; V(20) 35-37% (n = 12): 1 G5 lung and 1 G3
      reversible esophageal toxicity. For the whole group, local tumor recurrence
      occurred in 25% (95% confidence interval 14%-40%) of the patients, with 1 of 48
      (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal
      recurrence. The median actuarial overall survival was 20 months, with a 2-year
      survival rate of 36%. CONCLUSIONS: High-dose continuous hyperfractionated
      accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a
      biologic equivalent of approximately 80 Gy when delivered in conventional
      fractionation) in patients with inoperable NSCLC and a V(20) up to 37% is
      feasible.

PMID- 18037582
TI  - Tumor volume changes on 1.5 tesla endorectal MRI during neoadjuvant androgen
      suppression therapy for higher-risk prostate cancer and recurrence in men treated
      using radiation therapy results of the phase II CALGB 9682 study.
AB  - PURPOSE: We prospectively determined whether the change in tumor volume (TV)
      during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using
      conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was
      associated with the risk of recurrence after radiation (RT) and 6 months of AST.
      PATIENTS AND METHODS: Between 1997 and 2001, 180 men with clinical stage T1c
      T3cN0M0 adenocarcinoma of the prostate were registered. Fifteen were found to be
      ineligible and the institutional MR radiologist could not assess the TV in 32,
      leaving 133 for analysis. Multivariable Cox regression analysis was used to
      assess whether a significant association existed between eMRI-defined TV
      progression during nAST and time to recurrence adjusting for prostate-specific
      antigen (PSA) level, Gleason score (8 to 10 or 7 vs. 6 or less) and stage (T3 vs.
      T1-2). RESULTS: After a median follow up of 6.7 years and adjusting for known
      prognostic factors, there was a significant increase in the risk of PSA failure
      (HR, 2.3 [95% CI, 1.1-4.5; p = 0.025) in men with eMRI-defined TV progression
      during nAST. Specifically, adjusted estimates of PSA failure were significantly
      higher (p = 0.032) in men with, compared with men without, eMRI-defined TV
      progression reaching 38% vs. 19%, respectively, by 5 years. CONCLUSION:
      Eradicating intraprostatic hormone refractory prostate cancer (HRPC) by
      maximizing local control and randomized trials assessing whether survival is
      improved when agents active against HRPC are combined with maximal local therapy
      are needed in men who progress based on eMRI during nAST.

PMID- 18037583
TI  - Evaluation of sixth edition of AJCC staging system for nasopharyngeal carcinoma
      and proposed improvement.
AB  - PURPOSE: To evaluate the 6th edition of the International Union Against
      Cancer/American Joint Committee on Cancer staging system for nasopharyngeal
      carcinoma and to search for ways to improve the system. METHODS AND MATERIALS: We
      performed a retrospective review of data from 749 biopsy-proven nonmetastatic
      nasopharyngeal carcinoma patients. All patients had undergone contrast-enhanced
      computed tomography and had received radiotherapy as their primary treatment.
      RESULTS: The T stage, N stage, and stage group were significant, independent
      predictors for disease-specific death. No significant differences were found
      between Stage T2a and T1 in local failure-free survival or between Stage N3a and
      N2 in distant failure-free survival. Survival curves of the different T/N subsets
      showed a better segregation when T2a and N3a were downstaged to T1 and N2,
      respectively. The hazard ratio of disease-specific deaths for patients with T2N0
      disease was similar to that of patients with T1N0 disease; the same result was
      found for the T3N0 and T4N0 subsets. Downstaging the T2N0 subset to Stage I, T3N0
      to Stage II, and T4N0 to Stage III resulted in a more balanced patient
      distribution, better hazard consistency among subgroups, and improved hazard
      discrimination between overall stages. CONCLUSION: Using the 6th edition of the
      American Joint Committee on Cancer staging system produced an acceptable
      distribution of patient numbers and segregation of survival curves among the
      different stage groups. The prognostic accuracy of the staging system could be
      improved by recategorization of the T, N, and group stage criteria.

PMID- 18037584
TI  - Consensus guidelines for delineation of clinical target volume for intensity
      modulated pelvic radiotherapy in postoperative treatment of endometrial and
      cervical cancer.
AB  - PURPOSE: To develop an atlas of the clinical target volume (CTV) definitions for
      postoperative radiotherapy of endometrial and cervical cancer to be used for
      planning pelvic intensity-modulated radiotherapy. METHODS AND MATERIALS: The
      Radiation Therapy Oncology Group led an international collaboration of
      cooperative groups in the development of the atlas. The groups included the
      Radiation Therapy Oncology Group, Gynecologic Oncology Group, National Cancer
      Institute of Canada, European Society of Therapeutic Radiology and Oncology, and
      American College of Radiology Imaging Network. The members of the group were
      asked by questionnaire to define the areas that were to be included in the CTV
      and to outline theses areas on individual computed tomography images. The initial
      formulation of the group began in late 2004 and culminated with a formal
      consensus conference in June 2005. RESULTS: The committee achieved a consensus
      CTV definition for postoperative therapy for endometrial and cervical cancer. The
      CTV should include the common, external, and internal iliac lymph node regions.
      The upper 3.0 cm of the vagina and paravaginal soft tissue lateral to the vagina
      should also be included. For patients with cervical cancer, or endometrial cancer
      with cervical stromal invasion, it is also recommended that the CTV include the
      presacral lymph node region. CONCLUSION: This report serves as an international
      template for the definition of the CTV for postoperative intensity-modulated
      radiotherapy for endometrial and cervical cancer.

PMID- 18037585
TI  - Multi-institutional experience using the MammoSite radiation therapy system in
      the treatment of early-stage breast cancer: 2-year results.
AB  - PURPOSE: To present a retrospective multi-institutional experience of patients
      treated with the MammoSite radiation therapy system (RTS). METHODS AND MATERIALS:
      Nine institutions participated in a pooled analysis of data evaluating the
      clinical experience of the MammoSite RTS for delivering accelerated partial
      breast irradiation. Between 2000 and 2004, 483 patients were treated with the
      MammoSite RTS to 34 Gy delivered in 10 fractions. Treatment parameters were
      analyzed to identify factors affecting outcome. RESULTS: Median follow-up was 24
      months (minimum of 1 year). Overall, infection was documented in 9% of patients,
      but the rate was only 4.8% if the catheter was placed after lumpectomy. Six
      patients (1.2%) experienced an in-breast failure; four failures occurred remote
      from the lumpectomy site (elsewhere failure). Cosmetic results were
      good/excellent in 91% of patients. Treatment parameters identified as significant
      on univariate analysis were tested in multivariate regression analysis. The
      closed-cavity placement technique significantly reduced the risk of infection (p
      = 0.0267). A skin spacing of <6 mm increased the risk of severe acute skin
      reaction (p = 0.0178) and telangiectasia (p = 0.0280). The use of prophylactic
      antibiotics reduced the risk of severe acute skin reaction (p < 0.0001). The use
      of multiple dwell positions reduced the risk of severe hyperpigmentation (p =
      0.0278). Infection was associated with an increased risk of fair or poor overall
      cosmesis (p = 0.0009). CONCLUSIONS: In this series of patients, the MammoSite RTS
      seems to have acceptable toxicity rates and cosmetic outcomes, comparable to
      those with whole-breast radiotherapy. On the basis of these data, the closed
      cavity placement technique, use of prophylactic antibiotics, use of multiple
      dwell positions, and a minimum skin spacing of 6 mm seem to improve patient
      outcome.

PMID- 18037586
TI  - Chemoradiation for advanced head and neck cancer: potential for improving results
      to match those of current treatment modalities for early-stage tumors--long-term
      results of hyperfractionated chemoradiation with carbogen breathing and anemia
      correction with erythropoietin.
AB  - PURPOSE: To attempt to improve results of chemoradiation for head and neck
      cancer. METHODS AND MATERIALS: From March 1996 to April 2007, 98 patients with
      head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice
      daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1,
      13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment
      consisted of 5 mg/m(2) of carboplatin plus 115 cGy with carbogen breathing.
      Treatment was given 5 days per week up to total doses of 350 mg/m(2) of
      carboplatin plus 8050 cGy in 7 weeks. Anemia was corrected with erythropoietin.
      RESULTS: Ninety-six patients tolerated the treatment as scheduled. All patients
      tolerated the planned radiation dose. Local toxicity remained at the level
      expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven
      complete responses were achieved. After 11 years of follow-up (median, 81
      months), actuarial locoregional control, cause-specific survival, overall
      survival, and nodal control rates at 5 and 10 years were, respectively, 83% and
      83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease
      free survivors was 80 months. No significant differences in survival were
      observed between the different subsites or between the pretreatment node status
      groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3).
      CONCLUSIONS: Improving results of chemoradiation for advanced head and neck
      cancer up to the level obtained with current treatments for early-stage tumors is
      a potentially reachable goal.

PMID- 18037587
TI  - Reirradiation tolerance of the human brain.
AB  - PURPOSE: To give an overview of current available clinical data on reirradiation
      of glioma with respect to the tolerance dose of normal brain tissue. METHODS AND
      MATERIALS: Clinical brain reirradiation studies from January 1996 to December
      2006 were considered on radiation-induced late adverse effects-i.e., brain tissue
      necrosis. The studies were analyzed by using the linear quadratic model to derive
      information on the cumulative biologic effective tolerance dose (BED(cumulative))
      and equivalent doses in 2-Gy fractions (normalized total doses, NTD(cumulative))
      for the healthy human brain. RESULTS: The NTD(cumulative) in conventional
      reirradiation series (NTD(cumulative) of 81.6-101.9 Gy) were generally lower than
      in fractionated stereotactic radiotherapy (FSRT) (NTD(cumulative) of 90-133.9
      Gy.) or LINAC-based stereotactic radiosurgery series (NTD(cumulative) of 111.6
      137.2 Gy). No correlation between the time interval between the initial and
      reirradiation course and the incidence of radionecrosis was noted. The analysis
      showed the prescribed NTD(cumulative) to increase with decreasing treatment
      volume, which is allowed by modern conformal radiation techniques. CONCLUSION:
      Radiation-induced normal brain tissue necrosis is found to occur at
      NTD(cumulative) >100 Gy. The applied reirradiation dose and NTD(cumulative)
      increases with a change in irradiation technique from conventional to
      radiosurgery re-treatment, without increasing the probability of normal brain
      necrosis. Taken together, modern conformal treatment options, because of their
      limited volume of normal brain tissue exposure, allow brain reirradiation for
      palliative treatment of recurrent high grade glioma with an acceptable
      probability of radionecrosis.

PMID- 18037588
TI  - Postimplantation analysis enables improvement of dose-volume histograms and
      reduction of toxicity for permanent seed implantation.
AB  - PURPOSE: To demonstrate how postimplantation analysis is useful for improving
      permanent seed implantation and reducing toxicity. PATIENTS AND METHODS: We
      evaluated 197 questionnaires completed by patients after permanent seed
      implantation (monotherapy between 1999 and 2003). For 70% of these patients, a
      computed tomography was available to perform postimplantation analysis. The index
      doses and volumes of the dose-volume histograms (DVHs) were determined and
      categorized with respect to the date of implantation. Differences in symptom
      scores relative to pretherapeutic status were analyzed with regard to follow-up
      times and DVH descriptors. Acute and subacute toxicities in a control group of
      117 patients from an earlier study (June 1999 to September 2001) by Wust et al.
      (2004) were compared with a matched subgroup from this study equaling 110
      patients treated between October 2001 and August 2003. RESULTS: Improved
      performance, identifying a characteristic time dependency of DVH parameters
      (after implantation) and toxicity scores, was demonstrated. Although coverage
      (volume covered by 100% of the prescription dose of the prostate) increased
      slightly, high-dose regions decreased with the growing experience of the users.
      Improvement in the DVH and a reduction of toxicities were found in the patient
      group implanted in the later period. A decline in symptoms with follow-up time
      counteracts this gain of experience and must be considered. Urinary and sexual
      discomfort was enhanced by dose heterogeneities (e.g., dose covering 10% of the
      prostate volume, volume covered by 200% of prescription dose). In contrast,
      rectal toxicities correlated with exposed rectal volumes, especially the rectal
      volume covered by 100% of the prescription dose. CONCLUSION: The typical side
      effects occurring after permanent seed implantation can be reduced by improving
      the dose distributions. An improvement in dose distributions and a reduction of
      toxicities were identified with elapsed time between 1999 and 2003.

PMID- 18037589
TI  - Clofarabine acts as radiosensitizer in vitro and in vivo by interfering with DNA
      damage response.
AB  - PURPOSE: Combination treatment with radiotherapy and chemotherapy has emerged as
      the dominant form of cancer adjuvant regimens in recent years. Clofarabine, a
      newly approved drug for pediatric leukemia, is a second-generation purine
      nucleoside analogue that can block DNA synthesis and inhibit DNA repair.
      Therefore, we hypothesized that clofarabine could work synergistically with
      radiotherapy to increase the tumor cell response. METHODS AND MATERIALS: The
      effects of clofarabine on radiosensitivity have been established in several tumor
      cell lines in vitro and in vivo using colony-forming assays and tumor xenografts.
      The effect of clofarabine on the DNA damage response was also studied in vitro by
      measuring gamma-H2AX focus formation. RESULTS: Clonogenic survival was
      significantly reduced in irradiated cells treated with clofarabine, demonstrating
      the strong radiosensitizing effect of clofarabine. Furthermore, clofarabine
      displayed a radiosensitizing effect that was greater than gemcitabine or 5
      fluorouracil. We also found that low doses of clofarabine can prolong the
      presence of radiation-induced gamma-H2AX nuclear focus formation, and high doses
      of clofarabine can induce DNA double-strand breaks, suggesting that clofarabine
      can interfere with DNA damage response pathways. In addition, clofarabine-induced
      radiosensitization was also established in vivo using a colorectal cancer model,
      DLD-1, in athymic nude mice. When combined with fractionated radiotherapy, a
      moderate dose of clofarabine led to a significant increase in tumor growth
      inhibition. CONCLUSION: Clofarabine acts as a powerful radiosensitizer both in
      vitro and in vivo by interfering with the DNA damage response.

PMID- 18037592
TI  - [Reversal of Ballantyne's syndrome by selective fetal termination in a twin
      pregnancy].
AB  - OBJECTIVES: We describe Ballantyne's syndrome, a severe clinical materno-fetal
      entity, a pre-eclampsia-like disease. MATERIALS AND METHODS: We report the case
      of a woman with twin pregnancy presenting a Ballantyne's syndrome. Ultrasound
      examination at 22 weeks of gestation (wg), found heart abnormalities for one of
      the fetus. The ultrasonographic supervision revealed a fetal hydrops and at 28 wg
      a generalized maternal edema picture occurred. At this time, a Ballantyne's
      syndrome was suspected. RESULTS: A selective fetal termination of the affected
      twin was performed leading to a complete reversal of clinical and biochemical
      maternal picture, allowing the continuance of the pregnancy until 32 wg.
      CONCLUSION: Our article illustrates that when the diagnosis of Ballantyne's
      syndrome is quickly suspected and a treatable cause can be found, it allows
      sometimes a prenatal management and improves the materno-fetal prognosis.

PMID- 18037590
TI  - Effect of novel amplitude/phase binning algorithm on commercial four-dimensional
      computed tomography quality.
AB  - PURPOSE: Respiratory motion is a significant source of anatomic uncertainty in
      radiotherapy planning and can result in errors of portal size and the subsequent
      radiation dose. Although four-dimensional computed tomography allows for more
      accurate analysis of the respiratory cycle, breathing irregularities during data
      acquisition can cause considerable image distortions. The aim of this study was
      to examine the effect of respiratory irregularities on four-dimensional computed
      tomography, and to evaluate a novel image reconstruction algorithm using
      percentile-based tagging of the respiratory cycle. METHODS AND MATERIALS:
      Respiratory-correlated helical computed tomography scans were acquired for 11
      consecutive patients. The inspiration and expiration data sets were reconstructed
      using the default phase-based method, as well as a novel respiration percentile
      based method with patient-specific metrics to define the ranges of the
      reconstruction. The image output was analyzed in a blinded fashion for the phase-
      and percentile-based reconstructions to determine the prevalence and severity of
      the image artifacts. RESULTS: The percentile-based algorithm resulted in a
      significant reduction in artifact severity compared with the phase-based
      algorithm, although the overall artifact prevalence did not differ between the
      two algorithms. The magnitude of differences in respiratory tag placement between
      the phase- and percentile-based algorithms correlated with the presence of image
      artifacts. CONCLUSION: The results of our study have indicated that our novel
      four-dimensional computed tomography reconstruction method could be useful in
      detecting clinically relevant image distortions that might otherwise go unnoticed
      and to reduce the image distortion associated with some respiratory
      irregularities. Additional work is necessary to assess the clinical impact on
      areas of possible irregular breathing.

PMID- 18037591
TI  - Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by promoter
      hypermethylation in prostate tumor.
AB  - BACKGROUND: The prostate gland is the most common site of cancer and the third
      leading cause of cancer mortality in men. Solute carrier family 5 (iodide
      transporter), member 8 (SLC5A8) was proposed as a potential tumor suppressor gene
      which is silenced by epigenetic changes in various tumors. The aim of this study
      was to investigate the significance of DNA methylation in SLC5A8 expression in
      prostate tumors. METHODS: DNA methylation status of the promoter region and
      expression of SLC5A8 were evaluated in prostate cancer cell lines, tumor and
      adjacent non-tumor prostate tissues from same prostate cancer patients, by using
      bisulphite-modified sequencing, RT-PCR and quantitative methylation-specific PCR
      (QMSP) analysis. RESULTS: The reduced or lost expression of SLC5A8 was observed
      in 70% of the tumor tissues. The bisulphite-modified sequencing analysis on the
      prostate cancer cell lines which do not express SLC5A8 detected the densely
      methylated SLC5A8 promoter region. SLC5A8 was reactivated by treatment with DNA
      methyl transferase inhibitor, 5-azacytidine but not by trichostatin A (TSA).
      Higher methylation at the promoter region of SLC5A8 in primary prostate tumor
      tissues was detected as compared with those in adjacent non-tumor tissues (7/10,
      70%). CONCLUSIONS: These data suggested that DNA methylation in the SLC5A8
      promoter region suppressed the expression of SLC5A8 in prostate tumor.

PMID- 18037593
TI  - Development of a heat shock inducible gfp transgenic zebrafish line by using the
      zebrafish hsp27 promoter.
AB  - In the present study, a zebrafish hsp27 promoter was isolated and used to develop
      heat shock inducible gfp transgenic zebrafish. The endogenous hsp27 mRNAs were
      constitutively expressed from 4 hpf and increased in several regions of brain,
      heart and somites in early embryogenesis until 24 hpf. Subsequently, the
      expression was reduced significantly but maintained in the heart and ears. Heat
      shock induced hsp27 mRNAs in the blastoderm from 6 hpf and later in somites,
      branchial arches and several regions of brain. Similarly in hsp27-gfp transgenic
      zebrafish, constitutive GFP expression was observed from 11 hpf. GFP expression
      was mainly in the skin cells and increased to the peak level at 7 dpf, followed
      by a reduction. The constitutive GFP expression in the heart was initiated from
      50 hpf and maintained even in the adult fish. After heat shock, GFP expression
      was mainly induced in the muscle in addition to a mild increase in the skin and
      heart. The early stages of the embryos were more sensitive than late stages as
      the time required for induced GFP expression in the muscle is shorter. Thus, the
      hsp27-gfp transgenic line generally recapitulates the expression pattern and heat
      shock inducibility of endogenous hsp27 RNAs. We also tested the potential of
      using the hsp27-gfp transgenic zebrafish embryos for heavy metal induction and
      demonstrated the inducibility of GFP expression by arsenic; this pattern of
      induction was also supported by examination of endogenous hsp27 mRNA.

PMID- 18037594
TI  - Strain-dependence of age-related cochlear hearing loss in wild and domesticated
      Mongolian gerbils.
AB  - The Mongolian gerbil (Meriones unguiculatus) is one of the animal models in
      auditory research that has been used in several studies on age-related hearing
      loss. The standard laboratory strain is domesticated as it was bred in captivity
      for more than 70 years. We compared properties of distortion product otoacoustic
      emissions (DPOAEs) in domesticated gerbils with wild-type gerbils from F6-F7
      generations of a strain originating from animals trapped in Central Asia in 1995.
      Up to an age of 9months, DPOAE thresholds were comparable between both strains
      and were below 10dB SPL for f2 frequencies between 4 and 44kHz. In older
      domesticated animals, the thresholds were increased by up to 12dB. Significant
      increases were found at stimulus frequencies of 2kHz, 12-20kHz, and 56-60kHz. The
      best frequency ratio f2/f1 to evoke maximum DPOAE amplitude was larger in
      domesticated animals at the age of 9 months or older. While these data show that
      there is a deterioration of cochlear sensitivity due to domestication, the
      magnitude of the described changes is small. Thus, the general suitability of
      domesticated gerbils for auditory research seems not to be affected.

PMID- 18037595
TI  - First spike latency and spike count as functions of tone amplitude and frequency
      in the inferior colliculus of mice.
AB  - Spike counts (SC) or, spike rate and first spike latency (FSL), are both used to
      evaluate the responses of neurons to amplitudes and frequencies of acoustic
      stimuli. However, it is unclear which one is more suitable as a parameter for
      evaluating the responses of neurons to acoustic amplitudes and frequencies, since
      systematic comparisons between SC and FSL tuned to different amplitudes and
      frequencies, are scarce. This study systematically compared the precision and
      stability (i.e., the resolution and the coefficient variation, CV) of SC- and FSL
      function as frequencies and amplitudes in the inferior colliculus of mice. The
      results showed that: (1) the SC-amplitude functions were of diverse shape
      (monotonic, nonmonotonic and saturated) whereas the FSL-amplitude functions were
      in close registration, in which FSL decreased with the increase of amplitude and
      no paradoxical (an increase in FSL with increasing amplitude) or constant (an
      independence of FSL on amplitude) neuron was observed; (2) the discriminability
      (resolution) of differences in amplitude and frequency based on FSL are higher
      than those based on SC; (3) the CVs of FSL for low amplitude stimuli were smaller
      than those of SC; (4) the fraction of neurons for which BF=CF (within +/-500Hz)
      obtained from FSL was higher than that from SC at any amplitude of sound.
      Therefore, SC and FSL may vary, independent from each other and represent
      different parameters of an acoustic stimulus, but FSL with its precision and
      stability appears to be a better parameter than SC in evaluation of the response
      of a neuron to frequency and amplitude in mouse inferior colliculus.

PMID- 18037597
TI  - [Analysis of the ethical issues raised by a ten-year epidemiology program in
      French Guiana: limitations of the current legal framework and solutions adopted].
AB  - BACKGROUND: This paper discusses the ethical aspects of a large research program
      in virology, conducted since 1994 and which has evolved in parallel with the
      elaboration of bioethics laws in France. This research, which involved the
      collection of a considerable amount of epidemiological data in the field, focused
      on epidemiological determinants (mother to child transmission, genetic
      susceptibility/resistance) of the human oncogenic retrovirus human T cell
      lymphotropic virus type 1 (HTLV-1). Data were collected from a specific
      population (Noirs Marrons) living in remote areas in French Guiana (South
      America). This ethnic group of African descent is highly endemic for HTLV-1 and
      associated adult T cell leukemia/lymphoma. The population has lived for two
      centuries on either side of the Maroni river, which constitutes the frontier
      between French Guiana and Surinam. The low socioeconomic and education levels of
      a large part of this population are mainly explained by a recent
      housing/residence fixation on the French side of the Maroni river. It is also
      linked to significant immigration from Surinam due to the civil war, which lasted
      for five years in the late 1990s, in this country. Conducting epidemiological
      surveys in this peculiar context illustrates the limitations of the available
      current legal framework in France for such studies. Indeed, several important
      ethical issues arose concerning not only individual and population benefits, but
      also specificities of the given information and of the informed consent. Another
      question concerns individual information feed-back in such a context of
      persistent viral infection, with a very low disease incidence, in a population
      with a relatively low education level. The goal of this work was mainly to report
      several of the ethical issues encountered and to discuss possible ways of
      achieving better information deliver and consent procedures in such a context.
      Indeed, these procedures should include new ideas and regulations promoting a
      real partnership, in order to conduct long-term epidemiological studies in
      populations with a low education level.

PMID- 18037596
TI  - Gut modulatory, blood pressure lowering, diuretic and sedative activities of
      cardamom.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cardamom (Elettaria cardamomum) is traditionally
      used in various gastrointestinal, cardiovascular and neuronal disorders. AIM OF
      THE STUDY: To rationalize cardamom use in constipation, colic, diarrhea,
      hypertension and as diuretic. MATERIALS AND METHODS: Cardamom crude extract
      (Ec.Cr) was studied using in vitro and in vivo techniques. RESULTS: Ec.Cr caused
      atropine-sensitive stimulatory effect in isolated guinea-pig ileum at 3-10mg/ml.
      In rabbit jejunum preparations, Ec.Cr relaxed spontaneous and K+ (80 mM)-induced
      contractions as well as shifted Ca++ curves to right, like verapamil. Ec.Cr (3
      100mg/kg) induced fall in the arterial blood pressure (BP) of anaesthetized rats,
      partially blocked in atropinized animals. In endothelium-intact rat aorta, Ec.Cr
      relaxed phenylephrine (1 microM)-induced contractions, partially antagonized by
      atropine and also inhibited K+ (80 mM) contractions. In guinea-pig atria, Ec.Cr
      exhibited a cardio-depressant effect. Ec.Cr (1-10mg/kg) produced diuresis in
      rats, accompanied by a saluretic effect. It enhanced pentobarbital-induced
      sleeping time in mice. Bio-assay directed fractionation revealed the separation
      of spasmogenic and spasmolytic components in the aqueous and organic fractions
      respectively. CONCLUSION: These results indicate that cardamom exhibits gut
      excitatory and inhibitory effects mediated through cholinergic and Ca++
      antagonist mechanisms respectively and lowers BP via combination of both
      pathways. The diuretic and sedative effects may offer added value in its use in
      hypertension and epilepsy.

PMID- 18037598
TI  - Optimizing high-performance liquid chromatography method with fluorescence
      detection for quantification of tamoxifen and two metabolites in human plasma:
      application to a clinical study.
AB  - We set an improved high-performance liquid chromatography method with
      fluorescence detection HPLC-FLU assay with more sensitivity and precision for the
      quantification of tamoxifen and two metabolites: 4-hydroxytamoxifen and N
      desmethyltamoxifen. The compounds and internal standard, mexiletine, were
      separated with an Agilent Extend C18 column set at 65 degrees C and a mobile
      phase of methanol-1% triethylamine aqueous solution (pH 11; 82:18, v/v). The
      detection system utilized offline ultraviolet irradiation to convert the analytes
      to their respective photocyclisation products, followed by fluorescence detection
      (lambda ex=260 nm and lambda em=375 nm). The limits of quantification for
      tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen in plasma were improved to
      0.5, 0.5 and 0.1 ng/ml, respectively. And the retention times for tamoxifen, N
      desmethyltamoxifen and 4-hydroxytamoxifen were minimized to 11, 10 and 3.9 min,
      respectively. A single stage liquid-liquid extraction method for determination of
      these triphenylethylene drugs in plasma was developed, with high extraction
      efficiency and rapid sample treatment for target compounds. The method has been
      validated for use in a clinical bioavailability research of tamoxifen.

PMID- 18037599
TI  - Guidelines on good clinical laboratory practice: bridging operations between
      research and clinical research laboratories.
AB  - A set of Good Clinical Laboratory Practice (GCLP) standards that embraces both
      the research and clinical aspects of GLP were developed utilizing a variety of
      collected regulatory and guidance material. We describe eleven core elements that
      constitute the GCLP standards with the objective of filling a gap for laboratory
      guidance, based on IND sponsor requirements, for conducting laboratory testing
      using specimens from human clinical trials. These GCLP standards provide guidance
      on implementing GLP requirements that are critical for laboratory operations,
      such as performance of protocol-mandated safety assays, peripheral blood
      mononuclear cell processing and immunological or endpoint assays from biological
      interventions on IND-registered clinical trials. The expectation is that
      compliance with the GCLP standards, monitored annually by external audits, will
      allow research and development laboratories to maintain data integrity and to
      provide immunogenicity, safety, and product efficacy data that is repeatable,
      reliable, auditable and that can be easily reconstructed in a research setting.

PMID- 18037600
TI  - Informational needs in families after their child's mild head injury.
AB  - OBJECTIVE: When a child is hospitalized due to an illness or injury, the entire
      family may experience stress and/or anxiety. According to parents who have been
      in such a situation, providing adequate information is one of the most valuable
      ways to help the family deal with such feelings. Most mild head injuries suffered
      by children do not require hospitalisation and in such cases, their families
      should be provided with appropriate information in connection with their visit to
      the emergency ward. In the present study, family informational needs are
      characterized. METHODS: The families of 57 children who had suffered a mild head
      injury at 0-15 years of age answered one open-ended question. The analysis was
      carried out using content analysis. RESULTS: This analysis revealed two types of
      needs, i.e., a need for information concerning the head injury itself and how to
      provide care, as well as a need for reassurance and support in sharing and coping
      with the emotional burden. CONCLUSION: Despite differences in the severity of the
      child's head injury and requirement for hospitalisation, all the families
      expressed the same informational needs but also the need for emotional support.
      PRACTICE IMPLICATIONS: In connection with the treatment of children with head
      injuries, health-care personnel should provide the parents both with information
      concerning the injury and its treatment and with emotional support.

PMID- 18037601
TI  - Campus physicians' tobacco interventions with university students: a descriptive
      study of 16 Ontario university clinics.
AB  - OBJECTIVE: About one-quarter of Canadian post-secondary students smoke
      cigarettes. We examined how physicians from Ontario university health clinics
      intervene with these young adult smokers. METHOD: A convenience sample of 16
      universities was identified and surveys were hand-delivered to all 228 physicians
      from these schools. A total of 125 doctors (54.82%) responded; 70 were from
      universities that were involved in a government-sponsored, coordinated, multi
      campus, tobacco control initiative. RESULTS: Twenty percent of doctors reported
      asking all or almost all patients about tobacco use; 25.22% asked fewer than
      half. Describing how they respond to patients identified as smokers, 96.00% of
      physicians advised cessation, 72.00% offered assistance, and 64.00% arranged for
      follow-up. Doctors discussed patients' tobacco use with 78.59% of smokers.
      Nicotine replacement therapies were rarely offered to patients wanting to quit.
      Doctors from universities involved in the tobacco control initiative were more
      likely to keep patient education materials in the examining room. CONCLUSION:
      Because most doctors ask only some patients about tobacco use, they may be
      missing opportunities to provide appropriate advice and assistance to all
      smokers. PRACTICE IMPLICATIONS: Physician education and support to the clinic are
      needed to improve the frequency and quality of physician-delivered smoking
      cessation services to post-secondary students.

PMID- 18037602
TI  - Assessing validity of standardized patient ratings of medical students'
      communication behavior using the Roter interaction analysis system.
AB  - OBJECTIVE: The primary objective of this study is to examine concurrent validity
      of standardized patient (SP) ratings of second year medical students'
      communication skills with the Roter interaction analysis system (RIAS). METHODS:
      We designed An Integrated Medical Encounter (AIME), to teach second year medical
      students the link between communication and clinical reasoning with emphasis
      placed on understanding the connection between biomedical and psychosocial
      aspects of patient care. We randomized 120 students to intervention (AIME) and
      control groups (non-AIME). Students completed two post-intervention SP encounters
      which were videotaped and coded using RIAS. SPs used a 30-item checklist to rate
      students' communication behaviors. RESULTS: There were no differences between
      AIME and non-AIME students in age, ethnicity, gender, or college major; however,
      more AIME students reported prior health professional work. SPs rated AIME
      students' rapport-building skills higher (mean [S.E.]: 4.1 [0.15] vs. 3.9 [0.15],
      p=0.05); however, there were no differences in data gathering, patient
      education/counseling. RIAS demonstrated that AIME students more frequently used
      rapport-building statements (60.4 [2.7] vs. 52.1 [2.8], p=0.03). CONCLUSION: The
      RIAS confirmed SP ratings of differences in AIME and non-AIME students' rapport
      building skills. PRACTICE IMPLICATIONS: Future studies in medical education
      should further examine the minimum number of SP ratings needed to effectively
      evaluate communication skills curricula when resources are limited.

PMID- 18037603
TI  - Brief motivational interviewing for teens at risk of substance use consequences:
      a randomized pilot study in a primary care clinic.
AB  - The current study examined the impact of a brief motivational interviewing (MI)
      intervention (Project CHAT) on alcohol consumption and drug use for high-risk
      teens in a primary care clinic that provides health care for underserved
      populations. Youth (N=42, 48% male) were screened, and those eligible completed a
      baseline survey. Baseline survey completers were randomly assigned to usual care
      or to an MI intervention and completed a 3-month follow-up survey. The sample
      (age 12 to 18 years) was 85.7% Hispanic or Latino, 9.5% African American, and
      4.8% White. At the 3-month follow-up, Project CHAT teens reported less marijuana
      use, lower perceived prevalence of marijuana use, fewer friends who used
      marijuana, and lower intentions to use marijuana in the next 6 months, as
      compared to teens assigned to usual care. Providing this type of brief
      intervention is a viable approach to working with high-risk teens to decrease
      substance use.

PMID- 18037604
TI  - Predictors of changes in alcohol-related self-efficacy over 16 years.
AB  - Self-efficacy is a robust predictor of short- and long-term remission after
      treatment. This study examined the predictors of self-efficacy in the year after
      treatment and 15 years later. A sample of 420 individuals with alcohol use
      disorders was assessed five times over the course of 16 years. Predictors of self
      efficacy at 1 year included improvement from baseline to 1 year in heavy
      drinking, alcohol-related problems, depression, impulsivity, avoidance coping,
      social support from friends, and longer duration of participation in Alcoholics
      Anonymous (AA). Female gender, more education, less change in substance use
      problems, and impulsivity during the first year predicted improvement in self
      efficacy over 16 years. Clinicians should focus on keeping patients engaged in
      AA, addressing depressive symptoms, improving patient's coping, and enhancing
      social support during the first year and reduce the risk of relapse by monitoring
      individuals whose alcohol problems and impulsivity improve unusually quickly.

PMID- 18037605
TI  - Different changes in resistance index between uterine artery and uterine radial
      artery during early pregnancy.
AB  - BACKGROUND: Changes in blood flow impedance of the uterine artery (UA) and
      uterine radial artery (RA) which is in the lower-extremity of the UA were
      examined during early pregnancy. METHODS: Blood flow impedance was assessed by
      transvaginal color-pulsed-Doppler-ultrasonography in 72 women from weeks 4-16 of
      pregnancy and expressed as a resistance index (RI). RESULTS: RA-RI remained at
      the late-luteal phase level until the 5th week of pregnancy, decreased until the
      7th week, and remained low until the 10th week. UA-RI remained at the late-luteal
      phase level until the 10th week, and then gradually decreased until the 16th
      week. In nine women with spontaneous abortion, five out of six women with
      impaired growth of the gestational sac showed high RA-RI at the 6th week of
      pregnancy, whereas all three women with loss of fetal heart beat at the 8th week
      showed normal changes in RA-RI. CONCLUSIONS: Our results show different changes
      in blood flow impedance between the UA and RA during early pregnancy. A
      significant decrease of RA-RI after the 5th week may reflect vascular remodeling
      in the maternal-fetal interface at placentation, whereas a significant decrease
      of UA-RI after the 10th week may reflect changes of the whole uterine blood flow
      associated with uterine growth.

PMID- 18037606
TI  - Progestagen therapy for recurrent miscarriage.
AB  - BACKGROUND: Recurrent pregnancy loss (RM) affects 0.5-1% of couples. The
      pathophysiology of RM is complex. The suggested causes include anatomical,
      genetic and molecular abnormalities, endocrine disorders, thrombophilias and anti
      phospholipid syndrome. In approximately 50% of the cases neither of the above can
      be identified. We aimed at examining the evidence on the role of progesterone in
      the pathophysiology of RM, and the clinical evidence on effectiveness of
      progestogen treatment. METHODS: We searched PubMed and the Cochrane database
      covering the period of 1968-2007. The search terms progestogens and recurrent
      miscarriage, NK cells and recurrent miscarriage as well as cytokines and
      recurrent miscarriage were used. RESULTS: Progesterone is indispensable for
      creating a suitable endometrial environment for implantation. RM may be due to
      subnormal progesterone secretion and retarded endometrial development in the peri
      implantation period. Progesterone also acts on the immune system, mainly by
      affecting cytokine synthesis and the function of NK cells. A recent meta-analysis
      showed that though progesterone treatment did not affect pregnancy outcome in
      women with miscarriages in general, separate analysis of three small and dated
      studies including altogether 91 patients with RM revealed a small but significant
      effect. It is noteworthy that the design of these 40 years old studies does not
      meet modern requirements. CONCLUSION: Standardized laboratory protocols for
      identifying potential targets of progestogen treatment as well as implementation
      of well-designed randomized studies are needed to establish the usefulness of
      progesterone supplementation in the treatment of RM.

PMID- 18037607
TI  - Breakthroughs in genetic studies of ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS), the prototypic seronegative arthropathy, is known to
      be highly heritable, with >90% of the risk of developing the disease determined
      genetically. As with most common heritable diseases, progress in identifying the
      genes involved using family-based or candidate gene approaches has been slow. The
      recent development of the genome-wide association study approach has
      revolutionized genetic studies of such diseases. Early studies in ankylosing
      spondylitis have produced two major breakthroughs in the identification of genes
      contributing roughly one third of the population attributable risk of the
      disease, and pointing directly to a potential therapy. These exciting findings
      highlight the potential of future more comprehensive genetic studies of
      determinants of disease risk and clinical manifestations, and are the biggest
      advance in our understanding of the causation of the disease since the discovery
      of the association with HLA-B27.

PMID- 18037608
TI  - Aggressive CNS lupus vasculitis in the absence of systemic disease activity.

PMID- 18037609
TI  - The candidate lupus susceptibility gene Ifi202a is largely dispensable for B-cell
      function.

PMID- 18037610
TI  - Tissue and cell-specific localization of rice aquaporins and their water
      transport activities.
AB  - Water transport in plants is greatly dependent on the expression and activity of
      water transport channels, called aquaporins. Here, we have clarified the tissue-
      and cell-specific localization of aquaporins in rice plants by immunoblotting and
      immunocytochemistry using seven isoform-specific aquaporin antibodies. We also
      examined water transport activities of typical aquaporin family members using a
      yeast expression system in combination with a stopped-flow spectrophotometry
      assay. OsPIP1 members, OsPIP2;1, OsTIP1;1 and OsTIP2;2 were expressed in both
      leaf blades and roots, while OsPIP2;3, OsPIP2;5 and OsTIP2;1 were expressed only
      in roots. In roots, large amounts of aquaporins accumulated in the region
      adjacent to the root tip (around 1.5-4 mm from the root tip). In this region,
      cell-specific localization of the various aquaporin members was observed. OsPIP1
      members and OsTIP2;2 accumulated predominantly in the endodermis and the central
      cylinder, respectively. OsTIP1;1 showed specific localization in the rhizodermis
      and exodermis. OsPIP2;1, OsPIP2;3 and OsPIP2;5 accumulated in all root cells, but
      they showed higher levels of accumulation in endodermis than other cells. In the
      region at 35 mm from the root tip, where aerenchyma develops, aquaporins
      accumulated at low levels. In leaf blades, OsPIP1 members and OsPIP2;1 were
      localized mainly in mesophyll cells. OsPIP2;1, OsPIP2;3, OsPIP2;5 and OsTIP2;2
      expressed in yeast showed high water transport activities. These results suggest
      that rice aquaporins with various water transport activities may play distinct
      roles in facilitating water flux and maintaining the water potential in different
      tissues and cells.

PMID- 18037611
TI  - GEAR: genomic enrichment analysis of regional DNA copy number changes.
AB  - We developed an algorithm named GEAR (genomic enrichment analysis of regional DNA
      copy number changes) for functional interpretation of genome-wide DNA copy number
      changes identified by array-based comparative genomic hybridization. GEAR selects
      two types of chromosomal alterations with potential biological relevance, i.e.
      recurrent and phenotype-specific alterations. Then it performs functional
      enrichment analysis using a priori selected functional gene sets to identify
      primary and clinical genomic signatures. The genomic signatures identified by
      GEAR represent functionally coordinated genomic changes, which can provide clues
      on the underlying molecular mechanisms related to the phenotypes of interest.
      GEAR can help the identification of key molecular functions that are activated or
      repressed in the tumor genomes leading to the improved understanding on the tumor
      biology. AVAILABILITY: GEAR software is available with online manual in the
      website, http://www.systemsbiology.co.kr/GEAR/.

PMID- 18037612
TI  - Genome scale enzyme-metabolite and drug-target interaction predictions using the
      signature molecular descriptor.
AB  - MOTIVATION: Identifying protein enzymatic or pharmacological activities are
      important areas of research in biology and chemistry. Biological and chemical
      databases are increasingly being populated with linkages between protein
      sequences and chemical structures. There is now sufficient information to apply
      machine-learning techniques to predict interactions between chemicals and
      proteins at a genome scale. Current machine-learning techniques use as input
      either protein sequences and structures or chemical information. We propose here
      a method to infer protein-chemical interactions using heterogeneous input
      consisting of both protein sequence and chemical information. RESULTS: Our method
      relies on expressing proteins and chemicals with a common cheminformatics
      representation. We demonstrate our approach by predicting whether proteins can
      catalyze reactions not present in training sets. We also predict whether a given
      drug can bind a target, in the absence of prior binding information for that drug
      and target. Such predictions cannot be made with current machine-learning
      techniques requiring binding information for individual reactions or individual
      targets.

PMID- 18037613
TI  - Automatic synchronization and distribution of biological databases and software
      over low-bandwidth networks among developing countries.
AB  - Bioinformatics involves the collection, organization and analysis of large
      amounts of biological data, using networks of computers and databases. Developing
      countries in the Asia-Pacific region are just moving into this new field of
      information-based biotechnology. However, the computational infrastructure and
      network bandwidths available in these countries are still at a basic level
      compared to that in developed countries. In this study, we assessed the utility
      of a BitTorrent-based Peer-to-Peer (btP2P) file distribution model for automatic
      synchronization and distribution of large amounts of biological data among
      developing countries. The initial country-level nodes in the Asia-Pacific region
      comprised Thailand, Korea and Singapore. The results showed a significant
      improvement in download performance using btP2P--three times faster overall
      download performance than conventional File Transfer Protocol (FTP). This study
      demonstrated the reliability of btP2P in the dissemination of continuously
      growing multi-gigabyte biological databases across the three Asia-Pacific
      countries. The download performance for btP2P can be further improved by
      including more nodes from other countries into the network. This suggests that
      the btP2P technology is appropriate for automatic synchronization and
      distribution of biological databases and software over low-bandwidth networks
      among developing countries in the Asia-Pacific region. AVAILABILITY:
      http://everest.bic.nus.edu.sg/p2p/

PMID- 18037614
TI  - Antithrombin III in critically ill patients.

PMID- 18037615
TI  - Antithrombin III in critically ill patients: systematic review with meta-analysis
      and trial sequential analysis.
AB  - OBJECTIVE: To evaluate the benefits and harms of antithrombin III in critically
      ill patients. DESIGN: Systematic review and meta-analysis of randomised trials.
      DATA SOURCES: CENTRAL, Medline, Embase, International Web of Science, LILACS, the
      Chinese Biomedical Literature Database, and CINHAL (to November 2006); hand
      search of reference lists, contact with authors and experts, and search of
      registers of ongoing trials. REVIEW METHODS: Two reviewers independently selected
      parallel group randomised clinical trials comparing antithrombin with placebo or
      no intervention and extracted data related to study methods, interventions,
      outcomes, bias risk, and adverse events. Disagreements were resolved by
      discussion. Trials in any type of critically ill patients in intensive care were
      eligible. All trials, irrespective of blinding or language status, that compared
      any antithrombin III regimen with no intervention or placebo were included.
      Trials were considered to be at low risk of bias if they had adequate
      randomisation procedure, blinding, and used intention to treat analysis. Risk
      ratios with 95% confidence intervals were estimated with fixed and random effects
      models according to heterogeneity. MAIN OUTCOME MEASURES: Mortality, length of
      stay in intensive care or hospital, quality of life, severity of sepsis,
      respiratory failure, duration of mechanical ventilation, incidence of surgical
      intervention, intervention effect among various populations, and adverse events
      (such as bleeding). RESULTS: 20 trials randomly assigning 3458 patients met
      inclusion criteria. Eight trials had low risk of bias. Compared with placebo or
      no intervention, antithrombin III did not reduce overall mortality (relative risk
      0.96, 95% confidence interval 0.89 to 1.03). No subgroup analyses on risk of
      bias, populations of patients, or with and without adjuvant heparin yielded
      significant results. Antithrombin III increased the risk of bleeding events
      (1.52, 1.30 to 1.78). Heterogeneity was observed in only a few analyses.
      CONCLUSION: Antithrombin III cannot be recommended for critically ill patients
      based on the available evidence.

PMID- 18037617
TI  - SIMAP--structuring the network of protein similarities.
AB  - Protein sequences are the most important source of evolutionary and functional
      information for new proteins. In order to facilitate the computationally
      intensive tasks of sequence analysis, the Similarity Matrix of Proteins (SIMAP)
      database aims to provide a comprehensive and up-to-date dataset of the pre
      calculated sequence similarity matrix and sequence-based features like InterPro
      domains for all proteins contained in the major public sequence databases. As of
      September 2007, SIMAP covers approximately 17 million proteins and more than 6
      million non-redundant sequences and provides a complete annotation based on
      InterPro 16. Novel features of SIMAP include a new, portlet-based web portal
      providing multiple, structured views on retrieved proteins and integration of
      protein clusters and a unique search method for similar domain architectures.
      Access to SIMAP is freely provided for academic use through the web portal for
      individuals at http://mips.gsf.de/simap/and through Web Services for programmatic
      access at http://mips.gsf.de/webservices/services/SimapService2.0?wsdl.

PMID- 18037616
TI  - Early life determinants of physical activity in 11 to 12 year olds: cohort study.
AB  - OBJECTIVE: To examine factors in early life (up to age 5 years) that are
      associated with objectively measured physical activity in 11-12 year olds.
      DESIGN: Prospective cohort study. SETTING: Avon longitudinal study of parents and
      children, United Kingdom. PARTICIPANTS: Children aged 11-12 years from the Avon
      longitudinal study of parents and children. MAIN OUTCOME MEASURE: Physical
      activity levels in counts per minute (cpm) and minutes of moderate to vigorous
      physical activity for seven days measured with a uniaxial actigraph
      accelerometer. RESULTS: Valid actigraph data, defined as at least three days of
      physical activity for at least 10 hours a day, were collected from 5451 children.
      Several factors were associated with physical activity at ages 11-12 years.
      Regression coefficients are compared with the baseline of "none" for categorical
      variables: maternal brisk walking during pregnancy (regression coefficient 5.0,
      95% confidence interval -8.5 to 18.5; cpm for <1 h/wk and > or =2 h/wk of
      physical activity 17.7, 5.3 to 30.1), maternal swimming during pregnancy (21.5,
      10.9 to 32.1 and cpm for <1 h/wk and > or =2 h/wk of physical activity 24.2, 7.8
      to 40.7), parents' physical activity when the child was aged 21 months (28.5,
      15.2 to 41.8 and cpm of physical activity for either parent active and both
      parents active 33.5, 17.8 to 49.3), and parity assessed during pregnancy (2.9, 
      7.6 to 13.4 and cpm of physical activity for 1 and > or =2 parity 21.2, 7.1 to
      35.3). CONCLUSIONS: Few factors in early life predicted later physical activity
      in 11-12 year olds. Parents' physical activity during pregnancy and early in the
      child's life showed a modest association with physical activity of the child at
      age 11-12 years, suggesting that active parents tend to raise active children.
      Helping parents to increase their physical activity therefore may promote
      children's activity.

PMID- 18037618
TI  - High glucose decreases collagenase expression and increases TIMP expression in
      cultured human peritoneal mesothelial cells.
AB  - BACKGROUND: Peritoneal fibrosis (PF), a serious problem in long-term continuous
      ambulatory peritoneal dialysis (CAPD) patients, is characterized by extracellular
      matrix (ECM) accumulation which results from an imbalance between the synthesis
      and the degradation of ECM components. Previous studies have demonstrated that
      ECM synthesis is increased in human peritoneal mesothelial cells (HPMCs) under
      high glucose conditions, but the effects of high glucose on degradative pathways
      have not been fully explored. This study was undertaken to elucidate the effects
      of high glucose on these proteolytic processes in cultured HMPCs. METHODS: HPMCs
      were isolated from human omentum and were exposed to 5.6 mM glucose (NG), 5.6 mM
      glucose +34.4 mM mannitol (NG + M), or 40 mM glucose (HG) with or without PKC
      inhibitor (PKCi). Real-time PCR and western blot were performed to determine
      collagenases (MMP-1, -8 and -13) and TIMPs (TIMP-1 and -2) mRNA and protein
      expression, respectively. The individual activities of collagenases in culture
      media were determined by ELISA. RESULTS: Types I and III collagen protein
      expression were significantly increased in HG-conditioned media compared to NG
      media (P < 0.05). The MMP-1, -8 and -13/GAPDH mRNA ratios were significantly
      lower in HPMCs exposed to HG medium compared to NG cells by 64, 52 and 37%,
      respectively, and their protein expression by 76, 42 and 49%, respectively, in HG
      vs NG-conditioned media. The activities of collagenases in HG-conditioned media
      were also significantly lower than those in NG media (P < 0.05). In contrast, HG
      significantly increased TIMPs mRNA ratios and protein expression in HPMCs. These
      changes in collagenase and TIMP expression induced by HG were abrogated upon pre
      treatment with PKCi. CONCLUSION: In conclusion, impaired matrix degradation may
      contribute to ECM accumulation in PF.

PMID- 18037619
TI  - Venous stenosis in a pig arteriovenous fistula model--anatomy, mechanisms and
      cellular phenotypes.
AB  - BACKGROUND: Haemodialysis vascular access dysfunction is currently a huge
      clinical problem. Although arteriovenous (AV) fistulae are the preferred mode of
      dialysis access, they have significant problems with both early (failure to
      mature) and late fistula failure. Both are characterized radiologically as a
      stenosis of the venous segment. Despite the magnitude of the clinical problem,
      the exact pathogenesis of AV fistula failure remains unclear. The aim of this
      study was to develop and validate a pig model of AV fistula stenosis and then use
      it to dissect out the mechanisms responsible for this lesion. METHODS: AV
      fistulae were created between the femoral artery and vein of Yorkshire Cross
      pigs. Animals were sacrificed at 2 days, 7 days, 28 days and 42 days post
      surgery. At the time of sacrifice the entire specimen was divided into four
      regions; the arterial (AV-A) and venous (AV-V) portions of the AV anastomosis,
      the juxta-anastomotic segment (JA) and the proximal vein (PV), and assessed for
      the degree of intima-media thickening and the presence of specific cellular
      phenotypes. Haemodynamic parameters were not measured in this set of experiments.
      RESULTS: Significant luminal stenosis and intima-media thickening were present as
      early as 28 days and 42 days post-surgery in the pig model. In addition, within
      specimens from a single time point, these two parameters were maximal within the
      proximal vein and juxta-anastomotic segment as compared to the AV anastomosis (P
      < 0.0001). The vast majority of cells within the region of intima-media
      thickening were myofibroblasts. CONCLUSIONS: These studies suggest that early and
      aggressive intima-media thickening (which is made up primarily of myofibroblasts)
      plays an important role in AV fistula stenosis in a pig model of AV fistula
      placement. Interventions that target the mechanisms and cellular phenotypes
      described in this model, may be effective in reducing the very significant
      morbidity and economic costs currently associated with AV fistula failure.

PMID- 18037620
TI  - Matrix extracellular phosphoglycoprotein causes phosphaturia in rats by
      inhibiting tubular phosphate reabsorption.
AB  - BACKGROUND: Matrix extracellular phosphoglycoprotein (MEPE), first isolated from
      tumour-derived tissue from a patient with oncogenic hypophosphataemia, is a
      putative phosphatonin that has received much less attention than fibroblast
      growth factor-23. To date, its effect on renal tubular phosphate reabsorption
      remains undefined. METHODS: A renal clearance study was performed in
      anaesthetized rats infused intravenously with a range of doses of MEPE. RESULTS:
      MEPE had no effect on glomerular filtration rate (inulin clearance) but caused
      rapid, dose-dependent increases in absolute and fractional phosphate excretion,
      wholly attributable to reduced phosphate reabsorption. At a maximal dose, MEPE
      increased fractional phosphate excretion more than 2-fold, whereas no change was
      observed in time controls. CONCLUSION: The results lend support to the hypothesis
      that MEPE contributes to the phosphaturia of oncogenic hypophosphataemia and of
      hypophosphataemic rickets.

PMID- 18037621
TI  - Sensitivity analysis in summary measure of population health in France.
AB  - BACKGROUND: The aim of this study is to provide estimates of the French burden of
      disease, using the WHO Global Burden of Disease methodology and to perform
      sensitivity analysis on different set of mortality data. METHODS: The burden of
      disease is measured by disability-adjusted life years (DALYs) that take into
      account both mortality and morbidity data. Results were obtained using French
      mortality data for the years 2000 and 2001 and morbidity data estimated by WHO
      for France. Sensitivity analyses were conducted using different mortality data
      sets and various life tables as mortality norms. Calculations were also performed
      with and without discounting and age-weighting. RESULTS: In France, the annual
      burden of disease was about 12.4 million DALYs. Depending on the mortality data
      set and the choice of social values used for calculation, results could be quite
      different. The use of WHO estimates for mortality resulted in an underestimation
      of 2.6% of total DALYs with respect to French data. Changes of the mortality norm
      imply changes in the number of years of life lost (YLLs), whereas the use of
      discounting and age-weighting mainly modifies the ranking of diseases.
      CONCLUSION: DALYs constitute a summary measure of population health, which is a
      powerful tool for the grading of health problems, allowing to compare fatal and
      non-fatal diseases. Nevertheless, the validity of results obtained depends
      primarily on the validity of the input data. Collecting morbidity data (mainly
      incidence) at the national level is hence an important step in order to assess
      more accurately the specific burden of diseases in France.

PMID- 18037622
TI  - HSP90 as a marker of progression in melanoma.
AB  - BACKGROUND: HSP90 chaperones molecules critical for cell survival and malignant
      progression, including mutated B-raf. HSP90-targeting agents are in clinical
      trials. No large studies have been conducted on expression of HSP90 in melanomas.
      MATERIALS AND METHODS: Tissue microarrays containing 414 nevi, 198 primary and
      270 metastatic melanomas were assessed using our automated quantitative analysis
      (AQUA) method of in situ protein measurement; we use S-100 to define pixels as
      melanocytes (tumor mask) within the array spot, and measure HSP90 expression
      within the mask using Cy5-conjugated antibodies. RESULTS: HSP90 expression was
      higher in melanomas than nevi (P < 0.0001) and higher in metastatic than primary
      specimens (P < 0.0001). No association was seen between high HSP90 expression and
      survival in the primary or metastatic patient subsets. In primary melanomas, high
      HSP90 expression was associated with higher Clark level (P = 0.0167) and
      increased Breslow depth (P < 0.0001). CONCLUSIONS: HSP90 expression was
      significantly higher in tumors than nevi and was associated with disease
      progression, indicating that it might be a valuable drug target in melanoma, as
      well as a useful diagnostic marker. Prospective studies are needed to confirm the
      diagnostic role of HSP90, as well as the predictive role of HSP90 expression in
      patients treated with HSP90 inhibitors.

PMID- 18037623
TI  - Preoperative CA 15-3 and CEA serum levels as predictor for breast cancer
      outcomes.
AB  - BACKGROUND: To investigate the association between tumor markers [cancer antigen
      15-3 (CA 15-3) and carcinoembryonic antigen (CEA)] and clinicopathological
      parameters and patient outcomes in breast cancer. MATERIALS AND METHODS: A total
      of 740 patients with stages I-III breast cancer had preoperative CA 15-3 and CEA
      concentrations measured. Univariate and multivariate analyses were used to
      investigate associations between marker concentration and clinicopathological
      parameters and patient outcomes. RESULTS: Among 740 patients, elevated
      preoperative levels of CA 15-3 and CEA were identified in 92 (12.4%) and 79
      (10.7%) patients, respectively. Tumor size (>5 cm), node metastases (> or =4),
      and advanced stage (> or =III) were associated with higher preoperative levels.
      Elevated CA 15-3 and CEA levels were associated with poor disease-free survival
      (DFS, P = 0.0014, P = 0.0001, respectively) and overall survival (OS, P = 0.018,
      P = 0.015) even in stage-matched analysis. Patients with normal levels of both CA
      15-3 and CEA showed better DFS and OS than those with elevated group. In
      multivariate analysis, age (<35 years), tumor size (>2 cm), node metastases,
      estrogen receptor expression, and elevated CA 15-3 and CEA preoperative values
      were independent prognostic factors for DFS. CONCLUSION: High preoperative CA 15
      3 and CEA levels may reflect tumor burden and are associated with advanced
      disease and poor outcome. Measuring preoperative levels of CA 15-3 and CEA can be
      helpful for predicting outcomes.

PMID- 18037624
TI  - Ancestral LOXL1 variants are associated with pseudoexfoliation in Caucasian
      Australians but with markedly lower penetrance than in Nordic people.
AB  - Pseudoexfoliation syndrome is a generalized disorder of the extracellular matrix,
      characterized by the pathological accumulation of abnormal fibrillar material in
      the anterior segment of the eye predisposing to glaucomatous optic neuropathy. We
      investigated the role of lysyl oxidase-like 1(LOXL1) sequence variation in a
      Caucasian Australian population-based cohort of 2508 individuals, 86 (3.4%) of
      whom were diagnosed with pseudoexfoliation syndrome. Two non-synonymous variants
      in exon 1 of LOXL1 (Arg141Leu;Gly153Asp) were found to be strongly associated
      with pseudoexfoliation. Two copies of the high risk haplotype at these single
      nucleotide polymorphisms conferred a risk of 7.20 (95%CI: 3.04-20.75) compared
      with no copies of the high risk haplotype. Each of the disease-associated alleles
      is by far commoner in the normal population, and examination of cross-species
      homology reveals that the two disease-associated coding variants belong to the
      ancestral version of the gene. LOXL1 was found to be expressed by reverse
      transcription-polymerase chain reaction in all ocular tissues examined except
      retina. The presence of LOXL1 protein in ocular tissues of interest was
      demonstrated by western blotting. Specific bands of approximately 130 and 80 kDa,
      representing polymerized protein forms, were detected in the cornea, iris,
      ciliary body, lens capsule and optic nerve. The 42 kDa mature form of LOXL1 was
      detected in the iris and ciliary body. Our Caucasian population has a 9-fold
      lower lifetime incidence of pseudoexfoliation syndrome compared with Nordic
      populations despite having similar allelic architecture at the LOXL1 locus. This
      strongly suggests that as yet unidentified genetic or environmental factors
      independent of LOXL1 strongly influence the phenotypic expression of the
      syndrome.

PMID- 18037625
TI  - Anti-tumour necrosis factor treatment in patients with refractory systemic
      vasculitis associated with rheumatoid arthritis.
AB  - OBJECTIVE: To assess anti-tumour necrosis factor (anti-TNF) agents in patients
      with refractory systemic rheumatoid vasculitis (SRV). METHODS: 1200
      rheumatologists and internists were asked to provide medical files for patients
      with anti-TNF agents given as a second-line treatment for active SRV refractory
      to cyclophosphamide and glucocorticoids. RESULTS: We identified nine cases in
      which anti-TNF drugs were given for active SRV, despite previous treatment with a
      mean cumulative dose of 8.4 g of cyclophosphamide in association with high-dose
      glucocorticoids. The mean prednisone dose before anti-TNF therapy was 29.6
      mg/day. After 6 months, six patients were in remission (complete in five, partial
      in one). The treatment failed in one patient and two patients stopped taking the
      anti-TNF treatment due to side-effects. Mean prednisone dose was reduced to 11.2
      mg/day. Severe infection occurred in three patients. Relapses were observed in
      two patients. Remission was re-established by reintroducing anti-TNF therapy in
      one case and increasing the dose in the other. CONCLUSIONS: This study provides
      evidence of efficacy of anti-TNF therapy in adjunct to glucocorticoids for
      treating active refractory SRV. Remission was achieved in two-thirds of patients,
      with a significant decrease in prednisone dose, although there was a high rate of
      infection in these severely ill patients.

PMID- 18037626
TI  - Can ultrasonography improve on radiographic assessment in osteoarthritis of the
      hands? A comparison between radiographic and ultrasonographic detected pathology.
AB  - OBJECTIVES: Ultrasonography (US) is used in rheumatology to assess small joints
      in inflammatory arthritis. Recently there has been some investigation into the
      utility of US in osteoarthritis (OA), however there has been little comparison of
      US to other imaging modalities in OA. This study aimed to compare the detection
      of osteophytosis and joint space narrowing (JSN) by US and conventional
      radiography (CR) in OA of the hand. METHODS:  SUBJECTS: with OA of the hand
      underwent US and CR examination of the small joints of both hands to identify
      osteophytosis and joint space narrowing. RESULTS: 1106 joints of 37 patients were
      imaged with US and CR. US detected osteophytosis in 448 joints, compared to CR
      that detected osteophytosis in 228 joints (approximately 30% fewer joints). Where
      osteophytosis was detected by US but not CR, this was usually proximal to the
      joint line. Joint space narrowing was detected in 450 joints by US, but only 261
      joints by CR. The distribution of US and CR detected osteoarthritis changes in
      this cohort was consistent with population studies of radiographic hand OA,
      although metacarpophalangeal (MCP) involvement was higher than might be expected
      CONCLUSIONS: US detected more osteophytosis and joint space narrowing than CR in
      OA of the hand. Involvement of MCP joints was more common than would be expected
      from population radiographic studies. The increased detection of OA structural
      pathology by US may make this a useful tool for hand OA research.

PMID- 18037627
TI  - Everolimus in patients with rheumatoid arthritis receiving concomitant
      methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel
      group, proof-of-concept study.
AB  - OBJECTIVES: Everolimus, a proliferation signal inhibitor with disease-modifying
      properties, may be useful in treating rheumatoid arthritis (RA). This proof-of
      concept study assessed efficacy and safety of everolimus in combination with
      methotrexate (MTX) in patients with refractory RA. METHODS: A multi-centre,
      randomised, double-blind, placebo-controlled trial was performed in 121 patients
      with active RA receiving MTX. Patients were randomised to receive everolimus (6
      mg/day) or placebo. The primary endpoint was the American College of Rheumatology
      criteria for a 20% improvement in measures of disease activity (ACR20) at 12
      weeks. RESULTS: There was a rapid onset of action and at 12 weeks the ACR20
      response rate was significantly higher in the everolimus group (36.1%) than in
      the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and
      swollen joint counts, patient's assessment of pain, and patient's and physician's
      global assessment of disease activity were significantly greater after treatment
      with everolimus. The most common adverse events (AEs) in the everolimus group
      were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs
      8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment
      discontinuation were reported for 16.4% and 10.0% of patients, respectively.
      Changes in haematological parameters, liver function tests, and lipid levels
      occurred more frequently with everolimus compared to placebo, but were mild and
      reversible. CONCLUSIONS: The study indicates that everolimus plus MTX provides
      clinical benefit with an acceptable safety and tolerability profile. It may offer
      a new treatment option in RA patients with inadequate response to MTX.

PMID- 18037628
TI  - Scoring the nailfold microvascular changes during the capillaroscopic analysis in
      systemic sclerosis patients.
AB  - BACKGROUND: Longitudinal study to define a scoring system to quantify the
      specific capillary abnormalities, as observed by capillary microscopy in systemic
      sclerosis (SSc). METHODS: Ninety patients with SSc were evaluated by nailfold
      videocapillaroscopy for an average of 72 (SD 23) months. Enlarged and giant
      capillaries, haemorrhages, loss of capillaries, disorganisation of the
      microvascular array, and capillary ramifications were the evaluated parameters
      identifying the "scleroderma patterns". A semiquantitative rating scale to score
      these altered microvascular parameters was adopted (score 0-3). A
      "microangiopathy evolution score" (sum of three scores: loss of capillaries,
      disorganisation of the microvascular array and capillary ramifications) was also
      selected to assess the progression of the vascular damage. RESULTS: At the end of
      the follow-up, the score for each nailfold videocapillaroscopy parameter
      significantly changed. The microangiopathy evolution score significantly
      increased in 53 of 90 patients (59%) indicating a worsening of the
      microangiopathy. On the contrary, 22 patients (24%) showed a significant decrease
      of the evolution score suggesting an improvement of the microangiopathy and no
      changes were detected in 15 patients with SSc (17%). CONCLUSIONS: The
      capillaroscopic score was found to be a sensitive tool to quantify and monitor
      the SSc microvascular damage. Furthermore, the microangiopathy evolution score
      might be used to survey the evolution of the microvascular damage, as the
      relative scores increase during the progression of the SSc.

PMID- 18037630
TI  - Bilateral stimulation of the caudal zona incerta nucleus for tremor control.
AB  - INTRODUCTION: The ventrolateral (VL) nucleus of the thalamus is the commonly
      chosen target for deep brain stimulation (DBS) to alleviate tremor. However, it
      has a poor efficacy in alleviating proximal tremor and patients may develop
      tolerance to the action component of tremor. We performed bilateral stimulation
      of the caudal or motor part of the zona incerta nucleus (cZI) to determine its
      safety and efficacy in alleviating tremor. METHODS: 5 patients with parkinsonian
      tremor and 13 with a range of tremors (Holmes (HT), cerebellar (CT), essential
      (ET), multiple sclerosis (MS) and dystonic tremor (DT)) affecting both the
      proximal and distal body parts underwent MRI guided, bilateral cZI DBS. Tremor
      was assessed by the Fahn-Tolosa-Marin (FTM) tremor scale at baseline and at a
      mean follow-up of 12 months. RESULTS: Resting PD tremor improved by 94.8% and
      postural tremor by 88.2%. The total tremor score improved by 75.9% in 6 patients
      with ET. HT improved by 70.2%, proximal CT by 60.4% and proximal MS tremor by
      57.2% in the total tremor rating score. In the single patient with DT, there was
      improvement in both the dystonia and the tremor. Patients required low voltages
      of high-frequency stimulation and did not develop tolerance to it. Stimulation
      related side effects were transient. CONCLUSION: This prospective study shows
      that the cZI may be an alternative target for the treatment of tremor with DBS.
      In contrast to bilateral DBS of the VL nucleus, it improves all components of
      tremor affecting both the distal and proximal limbs as well as the axial
      musculature.

PMID- 18037629
TI  - Induction of parkinsonian resting tremor by stimulation of the caudal zona
      incerta nucleus: a clinical study.
AB  - INTRODUCTION: We hypothesise that parkinsonian tremor arises when the caudal zona
      incerta (cZI) and subthalamic nucleus (STN) are deprived of dopamine and become
      increasingly responsive to motor cortical alpha and beta frequency oscillations.
      These oscillations are synchronised and amplified through the basal ganglia
      thalamocortical loop and entrained into the cerebello-thalamocortical loop via
      the cZI. On receiving potent gamma-aminobutyric acid (GABA)-ergic alpha and beta
      frequency oscillations in cZI afferents, ventrolateral (VL) thalamocortical
      neurons become hyperpolarised and rebound burst fire, generating 4-6 Hz tremor
      oscillations. We test this hypothesis by stimulating the cZI at alpha and beta
      frequencies using deep brain stimulation (DBS) in non-tremulous parkinsonian
      patients to see whether a 4-6 Hz tremor can be induced. METHOD: This study
      included 11 patients with non-tremulous Parkinson's disease (PD), who had DBS
      leads implanted in a range of targets, including the cZI, STN, VL nucleus, globus
      pallidus internus (GPi), centromedian and parafascicular nucleus (CM/Pf), and the
      pedunculopontine nucleus (PPN). All patients underwent stimulation of active
      contacts within their respective targets at a standard pulse width, with
      frequencies ranging from 5 to 80 Hz up to a maximum tolerated voltage. The
      frequency of the tremor induced in the hands was recorded by accelerometry.
      RESULT: Resting tremor in the 4-6 Hz range could be readily induced following
      stimulation of the cZI and the VL nucleus between 5 and 40 Hz. Tremor was also
      seen following STN stimulation; however, this was only at high stimulation
      voltages (>5 volts). No tremor could be induced following CM/Pf, PPN or GPi
      stimulation. CONCLUSION: We discuss the implications of these findings and argue
      that resting tremor in PD is generated in the cortico-ZI-VL-thalamocortical loop
      rather than in the cortico-basal-ganglia-thalamocortical loop.

PMID- 18037631
TI  - Breaking butterflies on a wheel.

PMID- 18037643
TI  - Effects of neuromuscular electrical stimulation of the knee extensor muscles on
      muscle soreness and different serum parameters in young male athletes:
      preliminary data.
AB  - AIM: To evaluate the effects of neuromuscular electrical stimulation (NMES) on
      muscle soreness and on a variety of serum parameters during and after NMES of
      knee extensor muscles of young, well trained subjects over a study period of 96
      h. METHODS: Five male cyclists were included in this clinical observation. NMES
      (biphasic, asymmetric impulses) was applied through surface electrodes to both
      knee extensor muscles of each subject for 30 min. To determine changes in serum
      concentration of muscle proteins, blood samples were drawn at defined measure
      points before and after NMES. Muscle soreness was evaluated using a visual
      analogue scale at all measure points. RESULTS: There was a maximum (p<0.05) for
      "muscle pain" during stimulation but no significant changes could be detected
      after the stimulation period. Serum creatine kinase showed a peak with a
      significant increase (p<0.05) 24 h after NMES. Serum lactate levels only
      increased slightly (p = 0.08) during NMES. CONCLUSIONS: Although the changes of
      blood parameters measured in the present work correspond to those reported in the
      literature on eccentric strength training, no delayed onset muscle pain could be
      detected. Further studies should be carried out, also investigating different
      stimulation protocols in non-trained healthy subjects and in patients with less
      muscle mass.

PMID- 18037632
TI  - Physiological responses to rock climbing in young climbers.
AB  - Key questions regarding the training and physiological qualities required to
      produce an elite rock climber remain inadequately defined. Little research has
      been done on young climbers. The aim of this paper was to review literature on
      climbing alongside relevant literature characterising physiological adaptations
      in young athletes. Evidence-based recommendations were sought to inform the
      training of young climbers. Of 200 studies on climbing, 50 were selected as being
      appropriate to this review, and were interpreted alongside physiological studies
      highlighting specific common development growth variables in young climbers.
      Based on injury data, climbers younger than 16 years should not participate in
      international bouldering competitions and intensive finger strength training is
      not recommended. The majority of climbing foot injuries result from wearing too
      small or unnaturally shaped climbing shoes. Isometric and explosive strength
      improvements are strongly associated with the latter stages of sexual maturation
      and specific ontogenetic development, while improvement in motor abilities
      declines. Somatotyping that might identify common physical attributes in elite
      climbers of any age is incomplete. Accomplished adolescent climbers can now climb
      identical grades and compete against elite adult climbers aged up to and >40
      years. High-intensity sports training requiring leanness in a youngster can
      result in altered and delayed pubertal and skeletal development, metabolic and
      neuroendocrine aberrations and trigger eating disorders. This should be
      sensitively and regularly monitored. Training should reflect efficacious
      exercises for a given sex and biological age.

PMID- 18037646
TI  - Dentin matrix protein 1 (DMP1): new and important roles for biomineralization and
      phosphate homeostasis.
AB  - Previously, non-collagenous matrix proteins, such as DMP1, were viewed with
      little biological interest. The last decade of research has increased our
      understanding of DMP1, as it is now widely recognized that this protein is
      expressed in non-mineralized tissues, as well as in cancerous lesions. Protein
      chemistry studies have shown that the full length of DMP1, as a precursor, is
      cleaved into two distinct forms: the C-terminal and N-terminal fragments.
      Functional studies have demonstrated that DMP1 is essential in the maturation of
      odontoblasts and osteoblasts, as well as in mineralization via local and systemic
      mechanisms. The identification of DMP1 mutations in humans has led to the
      discovery of a novel disease: autosomal-recessive hypophosphatemic rickets.
      Furthermore, the regulation of phosphate homeostasis by DMP1 through FGF23, a
      newly identified hormone that is released from bone and targeted in the kidneys,
      sets a new direction for research that associates biomineralization with
      phosphate regulation.

PMID- 18037647
TI  - Efficacy of antibiotic prophylactic regimens for the prevention of bacterial
      endocarditis of oral origin.
AB  - Despite the controversy about the risk of individuals developing bacterial
      endocarditis of oral origin, numerous Expert Committees in different countries
      continue to publish prophylactic regimens for the prevention of bacterial
      endocarditis secondary to dental procedures. In this paper, we analyze the
      efficacy of antibiotic prophylaxis in the prevention of bacteremia following
      dental manipulations and in the prevention of bacterial endocarditis (in both
      animal models and human studies). Antibiotic prophylaxis guidelines remain
      consensus-based, and there is scientific evidence of the efficacy of amoxicillin
      in the prevention of bacteremia following dental procedures, although the results
      reported do not confirm the efficacy of other recommended antibiotics. The
      majority of studies on experimental models of bacterial endocarditis have
      verified the efficacy of antibiotics administered after the induction of
      bacteremia, confirming the efficacy of antibiotic prophylaxis in later stages in
      the development of bacterial endocarditis. There is no scientific evidence that
      prophylaxis with penicillin is effective in reducing bacterial endocarditis
      secondary to dental procedures in patients considered to be "at risk". It has
      been suggested that there is a high risk of severe allergic reactions secondary
      to prophylactically administered penicillins, but, in reality, very few cases
      have been reported in the literature. It has been demonstrated that antibiotic
      prophylaxis could contribute to the development of bacterial resistance, but only
      after the administration of several consecutive doses. Future research on
      bacterial endocarditis prophylactic protocols should involve the re-evaluation of
      the time and route of administration of antibiotic prophylaxis, and a search for
      alternative antimicrobials.

PMID- 18037648
TI  - Strong genetic control of emergence of human primary incisors.
AB  - Our understanding of tooth eruption in humans remains incomplete. We hypothesized
      that genetic factors contribute significantly to phenotypic variation in the
      emergence of primary incisors. We applied model-fitting to data from Australian
      twins to quantify contributions of genetic and environmental factors to variation
      in timing of the emergence of human primary incisors. There were no significant
      differences in incisor emergence times between zygosity groups or sexes.
      Emergence times of maxillary central incisors and mandibular lateral incisors
      were less variable than those of maxillary lateral incisors and mandibular
      central incisors. Maxillary lateral incisors displayed significant directional
      asymmetry, the left side emerging earlier than the right. Variation in timing of
      the emergence of the primary incisors was under strong genetic control, with a
      small but significant contribution from the external environment. Estimates of
      narrow-sense heritability ranged from 82 to 94% in males and 71 to 96% in
      females.

PMID- 18037649
TI  - Does psychological stress mediate social deprivation in tooth loss?
AB  - It is unclear which theoretical dimension of psychological stress affects health
      status. We hypothesized that both distress and coping mediate the relationship
      between socio-economic position and tooth loss. Cross-sectional data from 2915
      middle-aged adults evaluated retention of < 20 teeth, behaviors, psychological
      stress, and sociodemographic characteristics. Principal components analysis of
      the Perceived Stress Scale (PSS) extracted 'distress' (a = 0.85) and 'coping' (a
      =0.83) factors, consistent with theory. Hierarchical entry of explanatory
      variables into age- and sex-adjusted logistic regression models estimated odds
      ratios (OR) and 95% confidence intervals [95% CI] for retention of < 20 teeth.
      Analysis of the separate contributions of distress and coping revealed a
      significant main effect of coping (OR = 0.7 [95% CI = 0.7-0.8]), but no effect
      for distress (OR = 1.0 [95% CI = 0.9-1.1]) or for the interaction of coping and
      distress. Behavior and psychological stress only modestly attenuated socio
      economic inequality in retention of < 20 teeth, providing evidence to support a
      mediating role of coping.

PMID- 18037650
TI  - Numbers of natural teeth, diet, and nutritional status in US adults.
AB  - Evidence that dental status affects diet is equivocal. The hypothesis of this
      study was that diet was affected by dental status. The objective was to assess
      the relationship between numbers of teeth and diet and nutritional status in US
      adult civilians without prostheses. We examined 6985 NHANES (1988-1994)
      participants. Data included socio-economics, demographics, dental status, and
      diet and nutritional status. Dietary data were obtained from food frequency
      questionnaires and 24-hour dietary recall. Serum levels of beta carotene, folate,
      and vitamin C were measured with isocratic high-performance liquid
      chromatography. The population was classified by numbers of teeth. Covariance and
      Satterthwaite F-adjusted statistical comparisons were made between tooth
      groupings and the fully dentate population. Multilinear regression models
      adjusted for covariates. People with fewer than 28 teeth had significantly lower
      intakes of carrots, tossed salads, and dietary fiber than did fully dentate
      people, and lower serum levels for beta carotene, folate, and vitamin C. Dental
      status significantly affects diet and nutrition.

PMID- 18037651
TI  - Acidic proline-rich protein Db and caries in young children.
AB  - Polymorphic, acidic proline-rich proteins (PRPs) in saliva influence the
      attachment of bacteria associated with caries. Our aims were to detect one of
      three acidic PRP alleles of the PRH1 locus (Db) using polymerase chain-reaction
      (PCR) on genomic DNA, and to determine its association with caries. DNA was
      obtained from buccal swabs from Caucasian and African-American children, and
      their caries experience was recorded. PCR primers designed around exon 3 of the
      PRH1 locus gave a 416-base product representing Db and a 353-base product
      representing the other two alleles (Pa or Pif). In Caucasians, Db gene frequency
      was 14%, similar to Db protein from parotid saliva. In African-Americans,
      however, it was 37%, 18% lower than Db from parotid saliva (reported previously).
      Compared with African-Americans, all Caucasians had significantly greater
      Streptococcus mutans colonization, but only Db-negative Caucasians had
      significantly more caries. Alleles linked to Db may explain racial differences in
      caries experience.

PMID- 18037652
TI  - Predictors of obstructive sleep apnea-hypopnea treatment outcome.
AB  - Oral appliance therapy is an alternative to continuous positive airway pressure
      (CPAP) for treating the obstructive sleep apnea-hypopnea syndrome. However, the
      ability to pre-select suitable candidates for either treatment is limited. The
      aim of this study was to assess the value of relevant variables that can predict
      the outcome of oral appliance and CPAP therapy. Fifty-one patients treated with
      oral appliance therapy and 52 patients treated with CPAP were included. Relevant
      clinical, polysomnographic, and cephalometric variables were determined at
      baseline. The predictive value of variables for treatment outcome was evaluated
      in univariate and multivariate analyses. The outcome of oral appliance therapy
      was favorable, especially in less obese patients with milder sleep apnea and with
      certain craniofacial characteristics (mandibular retrognathism in particular).
      Neither univariate nor multivariate analyses yielded variables that reliably
      predicted the outcome of CPAP. We conclude that the variables found in this study
      are valuable for pre-selecting suitable candidates for oral-appliance therapy.

PMID- 18037653
TI  - Hypersensitivity to mechanical and intra-articular electrical stimuli in persons
      with painful temporomandibular joints.
AB  - This study tested whether persons with TMJ arthralgia have a modality-specific
      and site-specific hypersensitivity to somatosensory stimuli assessed by
      quantitative sensory tests (QST). Forty-three healthy persons and 20 with TMJ
      arthralgia participated. The QST consisted of: sensory and pain detection
      thresholds and summation threshold to intra-articular electrical stimulation,
      tactile and pin-prick sensitivity in the TMJ area, pressure-pain threshold and
      tolerance on the lateral side of the TMJ and on the finger. Persons with TMJ
      arthralgia had lower pain detection and summation thresholds (P < 0.001), higher
      ratings of tactile and pin-prick stimuli (P < 0.05), and markedly lower pressure
      thresholds on the TMJ and finger (P <0.001) than did healthy individuals.
      Correlation analysis revealed associations between several QST and clinical pain
      measures. This study provides new evidence of sensitization of the TMJs as well
      as central nociceptive pathways. QST may facilitate a mechanism-based
      classification of temporomandibular disorders.

PMID- 18037654
TI  - Effects of direct and indirect bleach on dentin fracture toughness.
AB  - There are concerns that tooth-whitening procedures irreversibly damage tooth
      structure. We investigated the hypothesis that dental bleaches significantly
      affect dentin structural integrity. The objective was to evaluate the effects of
      peroxide bleaches on dentin fracture toughness. Compact test specimens, composed
      of human dentin, were used (n = 10/group). Bleach (16% or 10% carbamide peroxide
      or 3% hydrogen peroxide) or control material, containing 0.1% sodium fluoride,
      was applied directly or indirectly to dentin through enamel (6 hrs/day) for 2 or
      8 weeks. Fracture toughness results were analyzed by ANOVA and Fisher's LSD test
      (p < 0.05). There were significant decreases in mean fracture toughness after two
      and eight-week direct (19-34% and 61-68%, respectively) and indirect (up to 17%
      and 37%, respectively) bleach application. The in vitro reduction in dentin
      fracture toughness caused by the application of peroxide bleaches was greater for
      the direct application method, longer application time, and higher bleach
      concentration.

PMID- 18037655
TI  - Consequences of viscoelastic behavior in the human temporomandibular joint disc.
AB  - The consequences of the viscoelastic behavior of the temporomandibular joint disc
      were analyzed in simulated jaw open-close cycles. It was hypothesized that
      viscoelasticity helps protect the underlying bone, while augmenting the
      smoothness of articular movements. Simulations were performed with a dynamic
      model of the masticatory system, incorporating the joints' cartilaginous
      structures as Finite Element Models. A non-linear viscoelastic material model was
      applied for the disc. The apparent stiffness of the disc to principal stress was
      largest when the jaw was closed, whereas, with the Von Mises' stress, it appeared
      largest when the jaw was open. The apparent stiffnesses appeared to be dependent
      on both the speed of the movements and the presence of a resistance between the
      teeth. It was concluded that the disc becomes stiffer when load concentrations
      can be expected. During continued cyclic motion, it softens, which favors
      smoothness of joint movement at the cost of damage prevention.

PMID- 18037656
TI  - A genome segment on mouse chromosome 12 determines maxillary growth.
AB  - The primary and modifier genes that regulate normal maxillofacial development are
      unknown. Previous quantitative trait locus (QTL) analyses using the F2 progeny of
      2 mouse strains, DBA/2J (short snout/wide face) and C57BL/6J (long snout/narrow
      face), revealed a significant logarithm-of-odds (LOD) score for snout length on
      mouse chromosome 12 at 44 centimorgan (cM). We further sought to validate this
      locus contributing to anterior-posterior dimensions of the upper mid-face at the
      D12Mit7 marker in a 44-centimorgan portion of chromosome 12. Congenic mice
      carrying introgressed DNA from DBA/2J on a C57BL/6J background were selected for
      submental vertex cephalometric imaging. Results confirmed QTLs, determining that
      short snout length (P < 0.05) and face width relative to snout length (P < 0.01)
      were present in the 44-cM region of chromosome 12. We conclude that one or more
      genes contributing to the shape of the maxillary complex are located near 44 cM
      of mouse chromosome 12.

PMID- 18037657
TI  - Healing cranial defects with AdRunx2-transduced marrow stromal cells.
AB  - Marrow stromal cells (MSCs) include stem cells capable of forming all mesenchymal
      tissues, including bone. However, before MSCs can be successfully used in
      regeneration procedures, methods must be developed to stimulate their
      differentiation selectively to osteoblasts. Runx2, a bone-specific transcription
      factor, is known to stimulate osteoblast differentiation. In the present study,
      we tested the hypothesis that Runx2 gene therapy can be used to heal a critical
      sized defect in mouse calvaria. Runx2-engineered MSCs displayed enhanced
      osteogenic potential and osteoblast-specific gene expression in vitro and in
      vivo. Runx2-expressing cells also dramatically enhanced the healing of critical
      sized calvarial defects and increased both bone volume fraction and bone mineral
      density. These studies provide a novel route for enhancing osteogenesis that may
      have future therapeutic applications for craniofacial bone regeneration.

PMID- 18037658
TI  - Osteogenic gene expression by human periodontal ligament cells under cyclic
      tension.
AB  - The forces that orthodontic appliances apply to the teeth are transmitted through
      the periodontal ligament (PDL) to the supporting alveolar bone, leading to the
      deposition or resorption of bone, depending upon whether the tissues are exposed
      to a tensile or compressive mechanical strain. To evaluate the osteogenic
      potential of PDL cells, we applied a 12% uni-axial cyclic tensile strain to
      cultured human PDL cells and analyzed the differential expression of 78 genes
      implicated in osteoblast differentiation and bone metabolism by real-time RT-PCR
      array technology. Sixteen genes showed statistically significant changes in
      expression in response to alterations in their mechanical environment, including
      cell adhesion molecules and collagen fiber types. Genes linked to the osteoblast
      phenotype that were up-regulated included BMP2, BMP6, ALP, SOX9, MSX1, and VEGFA;
      those down-regulated included BMP4 and EGF. This study has expanded our knowledge
      of the transcriptional profile of PDL cells and identified several new
      mechanoresponsive genes.

PMID- 18037659
TI  - Caries-related bacteria and cytokines induce CXCL10 in dental pulp.
AB  - Marked infiltration of inflammatory cells, such as activated T-cells, is observed
      in the progression of pulpitis; however, little is known about the mechanism of
      their recruitment into pulpal lesions. It has been recently demonstrated that CXC
      chemokine ligand 10 (CXCL10) chemoattracts CXC chemokine receptor 3 (CXCR3)
      positive activated T-cells. We therefore examined whether CXCL10 is involved in
      the pathogenesis of pulpitis. CXCL10 mRNA expression levels in clinically
      inflamed dental pulp were higher than those in healthy dental pulp.
      Immunostaining results revealed that CXCL10 was detected in macrophages,
      endothelial cells, and fibroblasts in inflamed dental pulp, and that CXCR3
      expression was observed mainly on T-cells. Moreover, cultured dental pulp
      fibroblasts produced CXCL10 after stimulation with live caries-related bacteria,
      peptidoglycans, and pro-inflammatory cytokines. In contrast, heat-killed bacteria
      did not induce CXCL10 secretion. These findings suggest that CXCL10-CXCR3 may
      play an important role in the pulpal immune response to caries-related bacterial
      invasion. ABBREVIATIONS: CXCL10, CXC chemokine ligand 10; CXCR3, CXC chemokine
      receptor 3; IFN, interferon; FBS, fetal bovine serum; LTA, lipoteichoic acid;
      PGN, peptidoglycan; IL, interleukin; TNF, tumor necrosis factor; PBS, phosphate
      buffered saline; ELISA, enzyme-linked immunosorbent assay; CCL, C-C chemokine
      ligand; TLR, Toll-like receptor; NOD, nucleotide oligomerization domain; HDPF,
      human dental pulp fibroblasts.

PMID- 18037660
TI  - Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2
      (UL44 and UL57) detects active infection in patients with chronic fatigue
      syndrome.
AB  - AIMS: To investigate whether the use of recombinant early antigens for detection
      of antibodies to human cytomegalovirus (HCMV) gene products CM(2) (UL44, UL57)
      and p52 (UL44) is specific in the diagnosis and differentiation of active HCMV
      infection in a subset of patients with chronic fatigue syndrome (CFS), a
      diagnosis which is often missed by the current ELISA assay that uses crude viral
      lysate antigen. METHODS: At a single clinic from 1999 to 2001, a total of 4774
      serological tests were performed in 1135 patients with patients using two
      immunoassays, Copalis and ELISA. The Copalis immunoassay utilised HCMV early gene
      products of UL44 and UL57 recombinant antigens for detection of HCMV IgM
      antibody, and viral capsid antigen for detection of HCMV IgG antibody. The ELISA
      immunoassay utilised viral crude lysate as antigen for detection of both HCMV IgG
      and IgM. RESULTS: 517 patients (45.6%) were positive for HCMV IgG by both assays.
      Of these, 12 (2.2%) were positive for HCMV(V) IgM serum antibody by HCMV ELISA
      assay, and 61 (11.8%) were positive for IgM HCMV serum antibody by Copalis assay.
      The Copalis assay that uses HCMV early recombinant gene products CM(2) (UL44,
      UL57) and p52 (UL44) in comparison with ELISA was 98% specific. CONCLUSIONS:
      Immunoassays that use early antigen recombinant HCMV CM(2) and p52 are five times
      more sensitive than HCMV ELISA assay using viral lysate, and are specific in the
      detection and differentiation of active HCMV infection in a subset of patients
      with CFS.

PMID- 18037662
TI  - Forkhead box A1 expression in breast cancer is associated with luminal subtype
      and good prognosis.
AB  - AIMS: Forkhead box A1 (FOXA1) is a forkhead family transcription factor expressed
      in breast cancer cells. It is essential for optimal expression of approximately
      50% of oestrogen receptor (ER)-related genes. This study explored the FOXA1
      relationship with luminal and basal breast cancer subtypes, proliferation
      markers, and survival in breast cancer patients who had received similar
      treatment. METHODS: A tissue microarray comprising tumours from 245 invasive
      breast cancer patients with 67 months of median follow-up was analysed for FOXA1
      expression by immunohistochemistry. Interpretable FOXA1 expression, obtained in
      184 patients, was analysed along with other variables such as tumour grade, size,
      nodal status, ER, progesterone receptor, HER2/neu, proliferation and basal
      markers. RESULTS: FOXA1 expression (score >3) was seen in 139 of 184 breast
      cancers. It correlated positively with ERalpha (p<0.0001), progesterone receptor
      (p<0.0001), and luminal subtype (p<0.0001); negatively with basal subtype
      (p<0.0001), proliferation markers and high histological grade (p = 0.0327).
      Univariate analysis showed nodal status, tumour grade, ER, progesterone receptor,
      FOXA1, basal markers and p53 as significant predictors of overall survival.
      Multivariate analysis showed that only nodal status (p = 0.0006) and ER (p =
      0.0017) were significant predictors of OS. In luminal subtype patient subgroup,
      FOXA1 expression was associated with better survival (p = 0.0284) on univariate
      analysis. CONCLUSION: Based on this study in patients treated with surgery
      followed by adjuvant anthracycline-based chemotherapy, FOXA1 expression is
      associated with good prognosis. It correlates with luminal subtype breast cancer,
      and could possibly serve as a clinical marker for luminal subtype A. Prognostic
      ability of FOXA1 in these low-risk breast cancers may prove to be useful in
      treatment decision making.

PMID- 18037661
TI  - Bone marrow micrometastasis in breast cancer: review of detection methods,
      prognostic impact and biological issues.
AB  - Immunocytochemical detection of disseminated tumour cells in the bone marrow of
      patients with primary breast cancer at surgery has been shown to be an
      independent prognostic factor in single institutional studies and in a large
      pooled analysis. However, bone marrow sampling and assessment of disseminated
      tumour cells is not a routine procedure in the clinical management of patients
      with breast cancer, but will certainly play a role in the near future for risk
      stratification and monitoring of therapeutic efficacy. Accurate identification of
      disseminated tumour cells in bone marrow must be based on standardised
      methodologies and procedures. This review describes these methodologies and the
      standardised morphological criteria used for disseminated tumour cell detection.
      The prognostic value of circulating tumour cells detection in peripheral blood is
      demonstrated in patients with metastatic disease but remains to be substantiated
      at early stage. The significance of disseminated tumour cells in bone marrow and
      in the blood for the prediction of response to therapy is briefly summarised.
      Finally, this review addresses the main biological questions raised by
      disseminated tumour cells, in particular understanding tumour dormancy and
      identifying metastatic stem cells.

PMID- 18037663
TI  - Multinucleate epithelial change in colorectal hyperplastic polyps: a review of 27
      cases.
AB  - AIM: To document the histological features of multinucleated epithelial giant
      cells (MEGs) in colorectal hyperplastic polyps and determine a possible
      aetiological agent. METHODS: Hyperplastic polyps were assessed for MEGs during
      the routine reporting at a private laboratory and public hospital laboratory. The
      histological features and clinical data were assessed, and immunohistochemical
      stains were performed to assess for viral infection (cytomegalovirus (CMV) and
      herpes simplex virus (HSV) 1 and 2) and to assist in the assessment of dysplasia
      (Ki-67, beta-catenin and p53). Ultrastructural examination was performed in one
      case. RESULTS: MEGs were identified in 27 polyps (24 patients). There was active
      inflammation in the polyps in nearly all cases (n = 24) and most showed changes
      in adjacent non-hyperplastic bowel mucosa such as focal basal cryptitis and
      apoptosis of crypt epithelium (16 patients). Immunohistochemistry for CMV, HSV
      and p53 was negative in all cases. The MEGs showed nuclear positivity for the
      proliferative marker Ki-67 and membranous positivity for beta-catenin.
      Ultrastructural studies failed to reveal viral particles. CONCLUSIONS: All the
      polyps containing MEGs showed active inflammation and apoptosis, and in most
      there was also focal inflammation and apoptosis in the adjacent mucosa.
      Inflammation in conjunction with the increased epithelial proliferation
      characteristics of hyperplastic polyps could be the mechanism for the MEG
      formation. In this series, all the polyps were associated with sodium phosphate
      bowel preparation (NaP) and the pro-inflammatory properties of NaP may be a
      stimulus for the induction of giant cells.

PMID- 18037664
TI  - Molecular techniques in cytopathology practice.
AB  - In the last decade, new molecular techniques were introduced into pathology
      laboratories. Cytology also benefited from the innovations emerging from this new
      era. Molecular cytopathology (MCP) can be defined as molecular studies applied on
      all types of cytological specimens, namely gynaecology cytology, exfoliative non-
      gynaecology cytology and fine needle aspirates. The development of many new
      ancillary techniques has paralleled the emergence of clinical cytology as a major
      diagnostic specialty. Clinical applications of these techniques have been growing
      in the last decade. The widespread acceptance of liquid-based systems in
      gynaecological cytology emphasises the relation between cells and molecules. The
      increased use of morphology and molecular biology in human papillomavirus-induced
      lesions for example, showed the potential to optimise, in one single brushed
      sample, diagnosis and research. Cytology samples from serous effusions, the
      pulmonary tree, urine, and aspirations, among others, are now likely to be
      studied by different molecular techniques for diagnosis, prognosis, or even
      assessment of therapeutic targets. In this review, the main published results
      concerning the application of molecular techniques in different fields of
      cytopathology are highlighted, and their applications discussed.

PMID- 18037665
TI  - Immunohistochemical markers as predictive tools for breast cancer.
AB  - Breast cancer is the predominant malignancy where oncologists use predictive
      markers clinically to select treatment options, with steroid receptors having
      been used for many years. Immunohistochemistry has taken over as the major assay
      method used for assessing markers. Despite its extensive use there are still
      issues around tissue fixation, methodology, interpretation and quantification.
      Although many markers have been evaluated, the oestrogen receptor remains the
      most reliable and best example of a predictor of treatment response. It is of
      major importance clinically that those undertaking interpretation of predictive
      markers understand the technical pitfalls and are aware of how expression of a
      particular marker relates to breast cancer pathology. A false negative or a false
      positive result will impact on patient management.

PMID- 18037666
TI  - Computing competition for light in the GREENLAB model of plant growth: a
      contribution to the study of the effects of density on resource acquisition and
      architectural development.
AB  - BACKGROUND AND AIMS: The dynamical system of plant growth GREENLAB was originally
      developed for individual plants, without explicitly taking into account
      interplant competition for light. Inspired by the competition models developed in
      the context of forest science for mono-specific stands, we propose to adapt the
      method of crown projection onto the x-y plane to GREENLAB, in order to study the
      effects of density on resource acquisition and on architectural development.
      METHODS: The empirical production equation of GREENLAB is extrapolated to stands
      by computing the exposed photosynthetic foliage area of each plant. The
      computation is based on the combination of Poisson models of leaf distribution
      for all the neighbouring plants whose crown projection surfaces overlap. To study
      the effects of density on architectural development, we link the proposed
      competition model to the model of interaction between functional growth and
      structural development introduced by Mathieu (2006, PhD Thesis, Ecole Centrale de
      Paris, France). KEY RESULTS AND CONCLUSIONS: The model is applied to mono
      specific field crops and forest stands. For high-density crops at full cover, the
      model is shown to be equivalent to the classical equation of field crop
      production (Howell and Musick, 1985, in Les besoins en eau des cultures; Paris:
      INRA Editions). However, our method is more accurate at the early stages of
      growth (before cover) or in the case of intermediate densities. It may
      potentially account for local effects, such as uneven spacing, variation in the
      time of plant emergence or variation in seed biomass. The application of the
      model to trees illustrates the expression of plant plasticity in response to
      competition for light. Density strongly impacts on tree architectural development
      through interactions with the source-sink balances during growth. The effects of
      density on tree height and radial growth that are commonly observed in real
      stands appear as emerging properties of the model.

PMID- 18037667
TI  - Remifentanil target-controlled infusion vs propofol target-controlled infusion
      for conscious sedation for awake fibreoptic intubation: a double-blinded
      randomized controlled trial.
AB  - BACKGROUND: Awake fibreoptic intubation (AFOI) is a technique used in patients
      with difficult airways. This study compares the suitability of remifentanil
      target-controlled infusion (TCI) to propofol TCI for conscious sedation during
      AFOI in patients with bona fide difficult airways. METHODS: We recruited 24, ASA
      I-III patients, who were undergoing sedation for elective AFOI. Patients were
      randomized to one of the two groups, Group P (n=10) received propofol TCI and
      Group R (n=14) received remifentanil TCI. Primary outcome measures were
      conditions achieved at endoscopy, intubation, and post-intubation, which were
      graded using scoring systems. Other parameters measured were the endoscopy time,
      intubation time, and number of attempts at intubation. A postoperative interview
      was conducted to determine recall of events and level of patient satisfaction.
      RESULTS: Endoscopy scores (0-5) and intubation scores (0-5) were significantly
      different [Group P 3 (1-4) vs Group R 1 (0-3) P<0.0001, Group P 3 (2-4) vs Group
      R 1 (0-3) P<0.0001, respectively]; with much better conditions in Group R,
      endoscopy times and intubation times were also significantly different, being
      shorter in Group R (P<0.007 and P<0.023, respectively). Patient tolerance of the
      procedure, judged by the discomfort scores (P<0.004) and the post-intubation
      scores (P<0.08), was significantly better in Group R. The level of recall for
      events was higher in Group R. However, there were no significant differences in
      the patient satisfaction scores. CONCLUSIONS: Remifentanil TCI appears to provide
      better conditions for AFOI when compared with propofol TCI. The disadvantage of
      remifentanil in this setting may be a higher incidence of recall.

PMID- 18037668
TI  - Should we use the rate-adaptive AV delay in cardiac resynchronization therapy
      pacing?
AB  - AIMS: Recommendations for programming the rate-adaptive AV delay in CRT. METHODS
      AND RESULTS: In cases of continual biventricular pacing, the optimal AV delay in
      CRT (AVD(opt)) is the net effect of the pacemaker-related interatrial conduction
      time (IACT), duration of the left-atrial electromechanical action (LA-EAC(long)),
      and the duration of the left-ventricular latency period (S(V)-EAC(short)). It can
      be calculated by AVD(opt) = IACT+LA-EAC(long)-S(V)-EAC(short). We measured these
      three components in 20 CRT-ICD patients during rest and submaximal ergo metric
      exercise (71 +/- 9 W) resulting in a 22.5 +/- 9.6 bpm rate increase. IACT and
      S(V)-EAC(short) did not reveal significant differences. LA-EAC(long), however,
      varied significantly by -10.7 +/- 16.1 ms (P = 0.008) during exercise. In
      contrast to AVD(optVDD), there was a significant difference in AVD(optDDD) of 
      8.8 +/- 14.5 ms (P = 0.014) between the resting and submaximal exercise
      conditions. In DDD pacing, AVD(opt) was shortened by 2.6 ms/10 bpm. CONCLUSION:
      In consideration of the findings of the studies performed to date, the rate
      adaptive AV delay should be deactivated.

PMID- 18037669
TI  - Sperm aneuploidy and meiotic sex chromosome configurations in an infertile XYY
      male.
AB  - BACKGROUND: There is little information regarding the behaviour of the extra Y
      chromosome during meiosis I in men with 47,XYY karyotypes and the segregation of
      the sex chromosomes in sperm. We applied immunofluorescent and FISH techniques to
      study the relationship between the sex chromosome configuration in meiotic germ
      cells and the segregation pattern in sperm, both isolated from semen samples of a
      47,XYY infertile man. METHODS: The sex chromosome configuration of pachytene germ
      cells was determined by immunostaining pachytene nuclei for synaptonemal complex
      protein 3 (SCP3) and SCP1. FISH was subsequently performed to identify the sex
      chromosomes and chromosome 18 in pachytene cells. Dual- and triple-color FISH was
      performed on sperm to analyse aneuploidy for chromosomes 13, 18, 21, X, and Y.
      RESULTS: 46,XY/47,XYY mosaic pachytene cells were observed (22.2% vs. 77.8%,
      respectively). The XYY trivalent, and X+YY configurations were most common. While
      the majority of sperm were of normal chromosomal constitution, an increase in sex
      and autosome disomy was observed. CONCLUSIONS: The level of germ cell moscaicism
      and their meiotic sex chromosome configurations may determine sperm aneuploidy
      rate and fertility status in 47,XYY men. Our approach of immunostaining meiotic
      cells in the ejaculate is a novel method for investigating spermatogenesis in
      infertile men.

PMID- 18037670
TI  - Circadian distribution of sleep phases after major abdominal surgery.
AB  - BACKGROUND: It is believed that the severely disturbed night-time sleep
      architecture after surgery is associated with increased cardiovascular morbidity
      with rebound of rapid eye movement (REM). The daytime sleep pattern of patients
      after major general surgery has not been investigated before. We decided to study
      the circadian distribution of sleep phases before and after surgery. METHODS:
      Eleven patients undergoing elective major abdominal surgery were included in the
      study. Continuous ambulatory polysomnographic monitoring was made 24 h before
      surgery and 36 h after surgery, thus including two nights after operation. Sleep
      was scored independently by two blinded observers and the recordings were
      reported as awake, light sleep (LS, stages I and II), slow wave sleep (SWS,
      stages III and IV), and REM sleep. RESULTS: There was significantly increased REM
      sleep (P=0.046), LS (P=0.020), and reduced time awake (P=0.016) in the
      postoperative daytime period compared with the preoperative daytime period. Five
      patients had REM sleep during the daytime after surgery. Three of these patients
      did not have REM sleep during the preceding postoperative night. There was
      significantly reduced night-time REM sleep for two nights after surgery compared
      with before surgery (P=0.001). CONCLUSIONS: Patients have significantly increased
      REM sleep, LS, and reduced time awake during the daytime period after surgery
      compared with before surgery. Disturbances in the circadian regulation of the
      sleep-wake cycle may be involved in the development of postoperative sleep
      disturbances.

PMID- 18037671
TI  - Regional cerebral metabolic rate (positron emission tomography) during inhalation
      of nitrous oxide 50% in humans.
AB  - BACKGROUND: Recent studies in man have shown that cerebral blood flow increases
      during inhalation of nitrous oxide (N2O), a finding which is believed to be a
      result of an increased cerebral metabolic rate (CMR). However, this has not
      previously been evaluated in man. METHODS: Regional CMR(glu) (rCMR(glu)) was
      measured three dimensionally with positron emission tomography (PET) after
      injection of 2-(18F)fluoro-2-deoxy-D-glucose in 10 spontaneously breathing men
      (mean age 31 yr) inhaling either N2O 50% in O2 30% or O2 30% in N2. RESULTS:
      Global CMR(glu) in young men was 27 (3) micromol 100 g(-1) min(-1) [mean (SD)].
      Inhalation of N2O 50% did not change global CMR(glu) [30 (5) micromol 100 g(-1)
      min(-1)] significantly, but it changed the distribution of the metabolism in the
      brain (P<0.0001 analysis of variance). Compared with inhalation of O2 30% in N2,
      N2O 50% inhalation increased the metabolism in the basal ganglia [14 (17)%,
      P<0.05] and thalamus [22 (23) %, P<0.05]. There was a prolonged metabolic effect
      of N2O inhalation seen on a succeeding PET scan with oxygen-enriched air
      (P<0.0001) performed 1 h after the N2O administration. CONCLUSIONS: Inhalation of
      N2O 50% did not change global CMR(glu), but the metabolism increased in central
      brain structures, an effect that was still present 1 h after discontinuation of
      N2O.

PMID- 18037672
TI  - Postoperative beneficial effects of esmolol in treated hypertensive patients
      undergoing laparoscopic cholecystectomy.
AB  - BACKGROUND: In an attempt to decrease haemodynamic instability and early
      postoperative complications such as nausea, vomiting, and pain, esmolol was added
      to the routine alfentanil infusion of patients with treated hypertension
      undergoing laparoscopic cholecystectomy. METHODS: Forty consecutive ASA class II
      patients with controlled hypertension about to undergo laparoscopic
      cholecystectomy were randomized into two groups: an esmolol group (Group E, n=20)
      was given a 1 mg kg(-1) bolus of esmolol and a placebo group (Group P, n=20) was
      given an identical volume of Ringer's lactate. The rate of esmolol infusion was
      adjusted to keep the heart rate between 65 and 75 beats min(-1) and was 5-10
      microg kg(-1) min(-1) throughout the procedure. After operation, patients
      reported their nausea using a four-point scale. RESULTS: Esmolol had an opioid
      sparing effect intraoperatively (P=0.001). Postoperative requirements for
      antiemetics were significantly less in the esmolol group, with no antiemetics
      given to eight patients. In the placebo group, however, all patients required at
      least one dose of antiemetic (P=0.007). The frequency of PONV did not correlate
      to the amounts of alfentanil, propofol, postoperative antiemetics consumed, or to
      female gender, non-smoking status, and history of PONV or motion sickness.
      Postoperative analgesic consumption in Group E was significantly lower than in
      Group P (P=0.012). CONCLUSIONS: Esmolol had an opioid-sparing effect in the
      intraoperative and immediate postoperative period in hypertensive patients
      undergoing laparoscopy. When combined with alfentanil, it was more effective than
      placebo in decreasing early PONV.

PMID- 18037673
TI  - Three type-B response regulators, ARR1, ARR10 and ARR12, play essential but
      redundant roles in cytokinin signal transduction throughout the life cycle of
      Arabidopsis thaliana.
AB  - Arabidopsis thaliana has 11 members belonging to the typical type-B ARR
      (authentic response regulator) family. Among them, seven highly homologous
      members appear also to be conserved in rice (Oryza sativa), but others are not.
      It was suggested that these seven ARRs are commonly implicated as DNA-binding
      transcription factors in the phosphorelay-mediated cytokinin signal transduction
      network in higher plants. To gain an insight into the functions of the cytokinin
      associated type-B ARRs, we previously investigated an arr1 arr10 arr12 triple
      mutant and reported that it exhibited stunted growth and abnormality in vascular
      development. Based on this fact, here we attempted to characterize the mutant
      intensively with reference to cytokinin-associated phenotypes through the life
      cycle. We showed that the observed cytokinin-associated phenotypes of arr1 arr10
      arr12 were very severe and highly analogous to those observed for certain ahk2
      ahk3 ahk4/cre1 triple mutants, which have virtually no cytokinin receptor to
      propagate the phosphorelay signal transduction network. Among the seven ARR
      members belonging to the cytokinin-associated type-B ARR subfamily, it was thus
      suggested that ARR1, ARR10 and ARR12 together play essential (or general) roles
      in cytokinin signal transduction. It is therefore conceivable that the other type
      B ARRs (ARR2, ARR11, ARR14 and ARR18) might play more specific roles spatially
      and temporally in plants.

PMID- 18037674
TI  - Analysis of GDP-D-mannose pyrophosphorylase gene promoter from acerola (Malpighia
      glabra) and increase in ascorbate content of transgenic tobacco expressing the
      acerola gene.
AB  - GDP-D-mannose pyrophosphorylase (GMP) is an important enzyme in the Smirnoff
      Wheeler's pathway for the biosynthesis of ascorbic acid (AsA) in plants. We have
      reported recently that the expression of the acerola (Malpighia glabra) GMP gene,
      designated MgGMP, correlates with the AsA content of the plant. The acerola plant
      has very high levels of AsA relative to better studied model plants such as
      Arabidopsis. Here we found that the GMP mRNA levels in acerola are higher than
      those from Arabidopsis and tomato. Also, the transient expression of the uidA
      reporter gene in the protoplasts of Nicotiana tabacum cultures showed the MgGMP
      gene promoter to have higher activity than the cauliflower mosaic virus 35S and
      Arabidopsis GMP promoters. The AsA content of transgenic tobacco plants
      expressing the MgGMP gene including its promoter was about 2-fold higher than
      that of the wild type.

PMID- 18037675
TI  - How should we use information about HWE in the meta-analyses of genetic
      association studies?
AB  - BACKGROUND: It is often recommended that control groups in meta-analyses of
      genetic association studies are checked for Hardy-Weinberg equilibrium (HWE) as a
      surrogate for assessing study quality. However, tests for HWE have low power and
      there is currently no consensus about how to handle studies that deviate
      significantly from HWE. METHODS: We identified 72 papers describing 114 meta
      analyses of 1603 primary gene-disease comparisons. Based on these studies and on
      related simulations, we evaluated four different strategies for handling studies
      that appear not to be in HWE: (i) include them in the meta-analysis; (ii) exclude
      them if the test for HWE results in P < 0.05; (iii) exclude them if a measure of
      the size of departure from HWE is large and (iv) exclude them if (ii) and (iii).
      RESULTS: Of the 72 papers, 26 did not report information on HWE, with a trend
      toward increased reporting with time. HWE was evaluated through testing, with
      only three papers assessing the size of departure. On re-analysis, 9% of the 1603
      primary comparisons showed significant deviation from HWE. The chance of an
      extreme departure from HWE was inversely related to the sample size of the study.
      Simulations suggest that there is no advantage in excluding studies that appear
      not to be in HWE. CONCLUSIONS: Meta-analyses should report both the magnitude and
      the statistical significance of departures from HWE. Studies that appear to
      deviate from HWE should be investigated further for weaknesses in their design,
      but these studies should not be excluded unless there are other grounds for
      doubting the quality of the study.

PMID- 18037676
TI  - Review of the effect of measles vaccination on the epidemiology of SSPE.
AB  - BACKGROUND: When measles vaccines were widely introduced in the 1970s, there were
      concerns that they might cause subacute sclerosing panencephalitis (SSPE): a very
      rare, late-onset, neurological complication of natural measles infection.
      Therefore, SSPE registries and routine measles immunization were established in
      many countries concurrently. We conducted a comprehensive review of the impact of
      measles immunization on the epidemiology of SSPE and examined epidemiological
      evidence on whether there was any vaccine-associated risk. METHODS: Published
      epidemiological data on SSPE, national SSPE incidence, measles incidence and
      vaccine coverage, reports of SSPE in pregnancy or shortly post partum were
      reviewed. Potential adverse relationships between measles vaccines and SSPE were
      examined using available data. RESULTS: Epidemiological data showed that
      successful measles immunization programmes protect against SSPE and, consistent
      with virological data, that measles vaccine virus does not cause SSPE. Measles
      vaccine does not: accelerate the course of SSPE; trigger SSPE or cause SSPE in
      those with an established benign persistent wild measles infection. Evidence
      points to wild virus causing SSPE in cases which have been immunized and have had
      no known natural measles infection. Perinatal measles infection may result in
      SSPE with a short onset latency and fulminant course. Such cases are very rare.
      SSPE during pregnancy appears to be fulminant. Infants born to mothers with SSPE
      have not been subsequently diagnosed with SSPE themselves. CONCLUSIONS:
      Successful measles vaccination programmes directly and indirectly protect the
      population against SSPE and have the potential to eliminate SSPE through the
      elimination of measles. Epidemiological and virological data suggest that measles
      vaccine does not cause SSPE.

PMID- 18037677
TI  - Leaf scorch symptoms are not correlated with bacterial populations during
      Pierce's disease.
AB  - Xylella fastidiosa (Xf) is a xylem-limited bacterium that lives as a harmless
      endophyte in most plant species but is pathogenic in several agriculturally
      important crops such as coffee, citrus, and grapevine (Vitis vinifera L.). In
      susceptible cultivars of grapevine, Xf infection results in leaf scorch,
      premature leaf senescence, and eventually vine death; a suite of symptoms
      collectively referred to as Pierce's disease. A qPCR assay was developed to
      determine bacterial concentrations in planta and these concentrations were
      related to the development of leaf-scorch symptoms. The concentration of Xf in
      leaves of experimental grapevines grown in the greenhouse was similar to the
      concentration of Xf in leaves of naturally infected plants in the field. The
      distribution of Xf was patchy within and among leaves. Some whole leaves
      exhibited severe leaf-scorch symptoms in the absence of high concentrations of
      Xf. Despite a highly sensitive assay and a range of Xf concentrations from 10(2)
      to 10(9) cells g(-1) fresh weight, no clear relationship between bacterial
      population and symptom development during Pierce's disease was revealed. Thus,
      high and localized concentrations of Xf are not necessary for the formation of
      leaf-scorch symptoms. The results are interpreted as being consistent with an
      atiology that involves a systemic plant response.

PMID- 18037678
TI  - Genetic and molecular regulation of fruit and plant domestication traits in
      tomato and pepper.
AB  - Tomato and pepper are two Solanaceous fruit crops that display an enormous
      diversity in fruit morphology. In this review, we will present an overview of the
      history of tomato and pepper and discuss key plant traits that were specifically
      selected during domestication of the two species. The traits discussed are fruit
      weight, shape, colour, ripening, pungency and plant architecture. We will review
      these characteristics as well as the genetic loci or genes that control these
      features, questioning whether mutations at orthologous loci occurred
      independently in these two species or whether unique plant and fruit features
      resulted in selection at different genes.

PMID- 18037679
TI  - Vascular flows and transpiration affect peach (Prunus persica Batsch.) fruit
      daily growth.
AB  - The relative contributions of xylem, phloem, and transpiration to fruit growth
      and the daily patterns of their flows have been determined in peach, during the
      two stages of rapid diameter increase, by precise and continuous monitoring of
      fruit diameter variations. Xylem, phloem, and transpiration contributions to
      growth were quantified by comparing the diurnal patterns of diameter change of
      fruits, which were then girdled and subsequently detached. Xylem supports peach
      growth by 70%, and phloem 30%, while transpiration accounts for approximately 60%
      of daily total inflows. These figures and their diurnal patterns were comparable
      among years, stages, and cultivars. Xylem was functional at both stage I and III,
      while fruit transpiration was high and strictly dependent on environmental
      conditions, causing periods of fruit shrinkage. Phloem imports were correlated to
      fruit shrinkage and appear to facilitate subsequent fruit enlargement. Peach
      displays a growth mechanism which can be explained on the basis of passive
      unloading of photoassimilates from the phloem. A pivotal role is played by the
      large amount of water flowing from the tree to the fruit and from the fruit to
      the atmosphere.

PMID- 18037680
TI  - Evidence for the presence of photorespiration in desiccation-sensitive leaves of
      the C4 'resurrection' plant Sporobolus stapfianus during dehydration stress.
AB  - The possible role of photorespiration as a general stress protection mechanism,
      and in C(4) plant metabolism, is controversial. In particular, the potential
      involvement of photorespiration in the acquisition of desiccation tolerance in
      'resurrection' plants is unknown. An investigation was carried out into whether
      photorespiration is present in leaves of the C(4) resurrection plant Sporobolus
      stapfianus Gandoger (Poaceae) and whether it functions as a mechanism of stress
      resistance in the desiccation-tolerant younger leaves (YL) of this plant. It is
      shown that the enzymes involved in the photorespiratory pathway maintain their
      activity until 88% relative water content (RWC) in both YL and desiccation
      sensitive older leaves (OL). In subsequent stages of dehydration stress, the
      enzymatic activity declined similarly in both YL and OL. The content of the
      phorespiratory metabolite, serine, and ethanolamine, a direct product of serine
      decarboxylation, is higher in the early stages of dehydration (88% RWC) in OL,
      suggesting a transiently enhanced photorespiratory activity in these leaves. This
      was confirmed by simultaneous gas exchange and fluorescence measurements, showing
      suppression of the electron transport rate in OL exposed to non-photorespiratory
      conditions (2% O(2)) at 85% RWC. It is concluded that a higher photorespiratory
      electron transport occurs in desiccation-sensitive OL, and it is therefore
      proposed that the capacity to scavenge excess electrons through photorespiration
      does not contribute to protect leaves of the desiccation-tolerant YL of S.
      stapfianus during the stress.

PMID- 18037681
TI  - Tonsillar and lymph node tuberculosis revealing asymptomatic pulmonary
      tuberculosis.

PMID- 18037682
TI  - Probabilistic path ranking based on adjacent pairwise coexpression for metabolic
      transcripts analysis.
AB  - MOTIVATION: Pathway knowledge in public databases enables us to examine how
      individual metabolites are connected via chemical reactions and what genes are
      implicated in those processes. For two given (sets of) compounds, the number of
      possible paths between them in a metabolic network can be intractably large. It
      would be informative to rank these paths in order to differentiate between them.
      RESULTS: Focusing on adjacent pairwise coexpression, we developed an algorithm
      which, for a specified k, efficiently outputs the top k paths based on a
      probabilistic scoring mechanism, using a given metabolic network and microarray
      datasets. Our idea of using adjacent pairwise coexpression is supported by recent
      studies that local coregulation is predominant in metabolism. We first evaluated
      this idea by examining to what extent highly correlated gene pairs are adjacent
      and how often they are consecutive in a metabolic network. We then applied our
      algorithm to two examples of path ranking: the paths from glucose to pyruvate in
      the entire metabolic network of yeast and the paths from phenylalanine to sinapyl
      alcohol in monolignols pathways of arabidopsis under several different microarray
      conditions, to confirm and discuss the performance analysis of our method.

PMID- 18037683
TI  - Identification of phylogenetically conserved microRNA cis-regulatory elements
      across 12 Drosophila species.
AB  - MOTIVATION: MicroRNAs are a class of endogenous small RNAs that play regulatory
      roles. Intergenic miRNAs are believed to be transcribed independently, but the
      transcriptional control of these crucial regulators is still poorly understood.
      RESULTS: In this work, phylogenetic footprinting is used to identify conserved
      cis-regulatory elements (CCEs) surrounding intergenic miRNAs in Drosophila. With
      a two-step strategy that takes advantage of both alignment-based and motif-based
      methods, we identified CCEs that are conserved across the 12 fly species. When
      compared with TRANSFAC database, these CCEs are significantly enriched in known
      transcription factor binding sites (TFBSs). Moreover, several TFs that play
      essential roles in Drosophila development (e.g. Adf-1, Abd-B, Sd, Prd, Ubx, Zen
      and En) are found to be preferentially regulating the miRNA genes. Further
      analysis revealed many over-represented cis-regulatory modules (CRMs) composed of
      multiple known TFBSs, motif pairs with significant distance constraints and a
      number of novel motifs, many of which preferentially occur near the transcription
      start site of protein-coding genes. Additionally, a number of putative miRNA-TF
      regulatory feedback loops were also detected. AVAILABILITY: Supplementary
      Material and the Perl scripts performing two-step phylogenetic footprinting are
      available at http://bioinfo.au.tsinghua.edu.cn/member/xwwang/mircisreg

PMID- 18037684
TI  - RReportGenerator: automatic reports from routine statistical analysis using R.
AB  - With the establishment of high-throughput (HT) screening methods there is an
      increasing need for automatic analysis methods. Here we present RReportGenerator,
      a user-friendly portal for automatic routine analysis using the statistical
      platform R and Bioconductor. RReportGenerator is designed to analyze data using
      predefined analysis scenarios via a graphical user interface (GUI). A report in
      pdf format combining text, figures and tables is automatically generated and
      results may be exported. To demonstrate suitable analysis tasks we provide direct
      web access to a collection of analysis scenarios for summarizing data from
      transfected cell arrays (TCA), segmentation of CGH data, and microarray quality
      control and normalization. AVAILABILITY: RReportGenerator, a user manual and a
      collection of analysis scenarios are available under a GNU public license on
      http://www-bio3d-igbmc.u-strasbg.fr/~wraff

PMID- 18037685
TI  - OEDIPE: a new graphical user interface for fast construction of numerical
      phantoms and MCNP calculations.
AB  - Although great efforts have been made to improve the physical phantoms used to
      calibrate in vivo measurement systems, these phantoms represent a single average
      counting geometry and usually contain a uniform distribution of the radionuclide
      over the tissue substitute. As a matter of fact, significant corrections must be
      made to phantom-based calibration factors in order to obtain absolute calibration
      efficiencies applicable to a given individual. The importance of these
      corrections is particularly crucial when considering in vivo measurements of low
      energy photons emitted by radionuclides deposited in the lung such as actinides.
      Thus, it was desirable to develop a method for calibrating in vivo measurement
      systems that is more sensitive to these types of variability. Previous works have
      demonstrated the possibility of such a calibration using the Monte Carlo
      technique. Our research programme extended such investigations to the
      reconstruction of numerical anthropomorphic phantoms based on personal
      physiological data obtained by computed tomography. New procedures based on a new
      graphical user interface (GUI) for development of computational phantoms for
      Monte Carlo calculations and data analysis are being developed to take advantage
      of recent progress in image-processing codes. This paper presents the principal
      features of this new GUI. Results of calculations and comparison with
      experimental data are also presented and discussed in this work.

PMID- 18037686
TI  - Tumor volume and uterine body invasion assessed by MRI for prediction of outcome
      in cervical carcinoma treated with concurrent chemotherapy and radiotherapy.
AB  - OBJECTIVE: The aim of this study was to evaluate the prognostic significance of
      primary tumor volume and uterine body invasion assessed by pre-treatment MRI for
      uterine cervical cancer patient treated with concurrent chemotherapy and
      radiotherapy. METHODS: A retrospective analysis of 106 patients with IB-IIIB
      cervical carcinoma was performed. Potential prognostic factors were stage,
      clinical tumor diameter, histology, age, pelvic lymph node, vaginal extension,
      parametrial invasion, tumor volume and uterine body invasion status. Multivariate
      analyses were performed to identify the prognostic factor for overall survival
      (OS) and disease-free survival (DFS). RESULTS: The 5-year OS, DFS rate were 59.7
      and 56.6%. Using multivariate analyses, a large tumor volume (>/=30 ml; P =
      0.012) and uterine body invasion (P = 0.020) and positive pelvic lymph node (LN)
      enlargement (P = 0.040) showed a significantly unfavorable influence on OS. Using
      these three factors, patients were divided into four subgroups: the OS rates of
      patients with risk 0 (volume <30 ml, no uterine body invasion, and negative LN),
      risk 1 (one of these three factors), risk 2 (two of these three factors) and risk
      3 (volume >/=30 ml, uterine body invasion, and positive LN) were 96.3, 77.5, 53.0
      and 14.8%, respectively (P < 0.0001). CONCLUSIONS: Tumor volume and uterine body
      invasion determined by MRI were significant prognostic factors for patients with
      cervical carcinoma. Pelvic lymph node enlargement diagnosed by CT also proved to
      be a significant prognostic factor in OS. Using these three parameters, we
      devised a practical and effective model to predict OS.

PMID- 18037688
TI  - Inter-observer agreement of standard joint counts in early rheumatoid arthritis:
      a comparison with grey scale ultrasonography--a preliminary study.
AB  - OBJECTIVES: The aims of the present study were to assess the inter-observer
      agreement of standard joint count and to compare clinical examination with grey
      scale ultrasonography (US) findings in patients with early rheumatoid arthritis
      (RA). METHODS: The study was conducted on 44 RA patients with a disease duration
      of <2 yrs. Clinical evaluation was performed independently by two rheumatologists
      for detection of tenderness in 44 joints and swelling in 42 joints. All patients
      underwent US assessment by a rheumatologist experienced in this method and
      blinded to the clinical findings. Joint inflammation was detected by US when
      synovial fluid and/or synovial hypertrophy was identified using OMERACT
      preliminary definitions. The inter-observer reliability was calculated by overall
      agreement (percentage of observed exact agreement) and kappa (kappa)-statistics.
      The reliability of US was calculated in 12 RA patients. RESULTS: There was fair
      to moderate inter-observer agreement on individual joint counts for either
      tenderness or joint swelling apart from the glenohumeral joint. US detected a
      higher number of inflamed joints than did clinical examination. The mean (+/
      S.D.) US joint count for joint inflammation was 19.1 (+/-4.1), while the mean (+/
      S.D.) number of swollen joints was 12.6 (+/-3.6), with a significant difference
      of P = 0.01. CONCLUSIONS: Our results provide evidence in favour of the
      hypothesis that clinical examination is far from optimal for assessing joint
      inflammation in patients with early RA. Furthermore, this study suggests that US
      can considerably improve the detection of signs of joint inflammation both in
      terms of sensitivity and reliability.

PMID- 18037687
TI  - Functional MRI in NPSLE patients reveals increased parietal and frontal brain
      activation during a working memory task compared with controls.
AB  - OBJECTIVES: Anatomical MRI brain scans may not reflect neurological dysfunction
      in patients with NPSLE. We used blood-oxygen-level-dependent functional MRI (BOLD
      fMRI) to investigate working memory function in NPSLE patients. METHODS: Twenty
      seven females took part: nine NPSLE patients (mean age 40 yrs; SLEDAI 10.9); nine
      RA patients and nine healthy controls. Subjects were tested using the n-back
      paradigm for working memory, where patients indicate when a stimulus matches one
      presented n trials previously. Functional scans used 3 mm slices x 30, repetition
      time 2570 ms, echo time 50 ms. Echo planar images were superimposed onto T1w
      anatomical images (Siemens 1.5 T). Data analysis used Brain Voyager QX Version
      1.7. RESULTS: During the memory task, there was activation in areas serving
      working memory, executive function and attention in all groups. Nine regions of
      interest were selected for activation during working memory (N-back task vs
      fixation, P < or = 0.005). In six out of nine regions, there was greater
      activation in the NPSLE group. This reached significance in three regions: the
      posterior inferior parietal lobules of both hemispheres [Brodmann area (BA) 7]
      separately and combined (P = 0.014, 0.016 and 0.004, respectively), and the
      supplementary motor area (mid-line frontal lobe) (BA32/6; P = 0.032).
      CONCLUSIONS: NPSLE patients showed greater frontoparietal activation than the
      other groups during the memory task, suggesting a greater need to recruit extra
      cortical pathways, possibly to supplement impaired function of standard pathways.

PMID- 18037689
TI  - Remote ablation of accessory pathways.

PMID- 18037690
TI  - Pilsicainide-induced Brugada-type ECG and ventricular arrhythmias originating
      from the left posterior fascicle in a case with Brugada syndrome associated with
      idiopathic left ventricular tachycardia.
AB  - The patient was a 50-year-old male in 2002, who was first suspected of having a
      Brugada-type electrocardiogram (ECG). A drug challenge test using pilsicainide
      was performed and unmasked a typical coved type ST elevation followed by
      ventricular arrhythmias (VAs) manifesting a QRS pattern with a right bundle
      branch block and left axis deviation. Three years later, he was transferred to
      the emergency room due to a wide QRS tachycardia with the same QRS morphology as
      the VA that previously occurred in the drug challenge test. An ECG just after the
      recorded termination of the tachycardia exhibited a typical Brugada-type ECG. In
      an electrophysiological study, ventricular fibrillation could be easily induced
      with reproducibility. Since the clinical tachycardia could not be sustained by an
      isoproterenol infusion, mapping and catheter ablation targeting the pilsicainide
      induced VAs was performed. The successful ablation site was the left mid-lower
      septal wall where a Purkinje potential was recorded and a false tendon was
      attached just to it.

PMID- 18037691
TI  - Production of a recombinant Fab in Pichia pastoris from a Monocistronic
      expression vector.
AB  - Recombinant Fab is usually expressed using dicistronic vectors producing the
      heavy and light chains separately. We developed an improved vector for Fab
      fragment expression in Pichia pastoris, which allows a stoichiometric expression
      of both chains based on a monocistronic arrangement. The protein is produced as a
      unique polypeptide harbouring a KEX2 processing site between both chains. After
      KEX cleavage, a correctly folded mature Fab is formed. The produced recombinant
      protein is characterized as a heterodimeric functional Fab. The vector described
      is a new tool for the proper expression of antibody fragments or any
      heterodimeric polypeptides.

PMID- 18037692
TI  - Changes in the glomerular filtration rate of 27 cats with hyperthyroidism after
      treatment with radioactive iodine.
AB  - Hyperthyroidism is a common endocrinopathy of older cats and is associated with
      an increased glomerular filtration rate (gfr). Renal dysfunction is also common
      in older cats and may develop after they have been treated for hyperthyroidism.
      This paper describes the changes in the gfr of 27 hyperthyroid cats in the six
      months after their treatment with radioactive iodine ((131)I), and evaluates
      whether any commonly measured pretreatment parameters (serum biochemistry,
      systolic blood pressure, urine specific gravity) could predict a clinically
      significant decline in renal function. The gfr of all the cats had decreased one
      month after treatment, and the mean gfr was significantly lower. There was no
      further significant change in gfr between one and six months. The only
      independent variable associated with the final gfr was the pretreatment plasma
      glucose concentration (P=0.003).

PMID- 18037693
TI  - Comparison of five real-time PCR assays for detecting virulence genes in isolates
      of Escherichia coli from septicaemic neonatal foals.
AB  - Fifty-five isolates of Escherichia coli from septicaemic neonatal foals were used
      to validate five real-time pcr assays targeting different known virulence factor
      genes: curli fibre (csgD), ferric hydroxamate uptake (fhuA), type 1A pilin
      (fimA), aerobactin (lutA) and yersiniabactin (fyuA). A pcr assay targeting a
      universal sequence of the bacterial 16S rrna gene served as quality control. The
      pcr assays showed good analytical specificity and sensitivity on the basis of
      sequencing the pcr products, their lack of cross-reactivity with non-E coli
      organisms, high amplification efficiency and a limit of detection as low as 25 E
      coli colony-forming units. There were differences between the detection rates and
      amplification efficiencies for the five virulence genes. The pcr assays targeting
      genes csgD, fhuA and fyuA were able to detect all 55 E coli isolates, with gene
      csgD having the best amplification efficiency. The lowest detection rate and
      amplification efficiency of the E coli isolates was found for the lutA gene.

PMID- 18037694
TI  - Microbiological differences between cull cattle slaughtered at an abattoir and
      cull cattle slaughtered on farms.
AB  - Tissue samples from 27 casualty adult dairy cattle slaughtered on farms and 32
      'normal' cull dairy cattle were analysed microbiologically for total viable
      counts (tvc), Enterobacteriaceae, Escherichia coli o157, Salmonella enterica and
      Campylobacter species. Overall the counts of Enterobacteriaceae and tvc were
      higher in the animals slaughtered on farms, particularly in the spleen. One
      'normal' animal yielded E coli O157, and one yielded Campylobacter jejuni, and
      eight of the cattle slaughtered on farms yielded C jejuni and five yielded S
      enterica.

PMID- 18037695
TI  - Efficacy of a combination ivermectin/praziquantel paste against nematodes,
      cestodes and bots in naturally infected ponies.

PMID- 18037696
TI  - Fungal pyelonephritis due to Cladophialophora bantiana in a cat.

PMID- 18037697
TI  - Possible nutritionally induced copper-associated chronic hepatitis in two dogs.

PMID- 18037698
TI  - Use of the medicines cascade.

PMID- 18037699
TI  - Micotil: safe use and administration.

PMID- 18037700
TI  - Time to recognise experienced unqualified nurses?

PMID- 18037701
TI  - Medicated feedingstuffs prescriptions.

PMID- 18037702
TI  - Licence to practise.

PMID- 18037706
TI  - Secretory phospholipase A2 increases SR-BI-mediated selective uptake from HDL but
      not biliary cholesterol secretion.
AB  - High density lipoprotein cholesterol represents a major source of biliary
      cholesterol. Secretory phospholipase A2 (sPLA2) is an acute phase enzyme
      mediating decreased plasma HDL cholesterol levels. Clinical studies reported a
      link between increased sPLA2 expression and the presence of cholesterol
      gallstones. The aim of our study was to investigate whether the overexpression of
      human sPLA2 in transgenic mice affects biliary cholesterol secretion and
      gallstone formation. Liver weight (P < 0.01) and hepatic cholesterol content (P <
      0.01) were significantly increased in sPLA2 transgenic mice compared with
      controls as a result of increased scavenger receptor class B type I (SR-BI)
      mediated hepatic selective uptake of HDL cholesterol (P < 0.01), whereas hepatic
      SR-BI expression remained unchanged. However, biliary cholesterol secretion as
      well as fecal neutral sterol and fecal bile salt excretion remained unchanged in
      sPLA2 transgenic mice. Furthermore, gallstone prevalence in response to a
      lithogenic diet was identical in both groups. These data demonstrate that i)
      increased flux of cholesterol from HDL into the liver via SR-BI as a result of
      phospholipase modification of the HDL particle translates neither into increased
      biliary and fecal sterol output nor into increased gallstone formation, and ii)
      increased sPLA2 expression in patients with cholesterol gallstones might be a
      consequence rather than the underlying cause of the disease.

PMID- 18037707
TI  - Rapid oral fluid-based point-of-care HIV testing: applicability in developing
      countries.

PMID- 18037705
TI  - Getting in sync with dimeric Eg5. Initiation and regulation of the processive
      run.
AB  - Eg5/KSP is the kinesin-related motor protein that generates the major plus-end
      directed force for mitotic spindle assembly and dynamics. Recent work using a
      dimeric form of Eg5 has found it to be a processive motor; however, its
      mechanochemical cycle is different from that of conventional Kinesin-1. Dimeric
      Eg5 appears to undergo a conformational change shortly after collision with the
      microtubule that primes the motor for its characteristically short processive
      runs. To better understand this conformational change as well as head-head
      communication during processive stepping, equilibrium and transient kinetic
      approaches have been used. By contrast to the mechanism of Kinesin-1, microtubule
      association triggers ADP release from both motor domains of Eg5. One motor domain
      releases ADP rapidly, whereas ADP release from the other occurs after a slow
      conformational change at approximately 1 s(-1). Therefore, dimeric Eg5 begins its
      processive run with both motor domains associated with the microtubule and in the
      nucleotide-free state. During processive stepping however, ATP binding and
      potentially ATP hydrolysis signals rearward head advancement 16 nm forward to the
      next microtubule-binding site. This alternating cycle of processive stepping is
      proposed to terminate after a few steps because the head-head communication does
      not sufficiently control the timing to prevent both motor domains from entering
      the ADP-bound state simultaneously.

PMID- 18037708
TI  - Quest for universal red cell units.

PMID- 18037709
TI  - Miliary tuberculosis & its sequelae.

PMID- 18037710
TI  - Locally available & natural therapeutic foods for immunomodulation in protein
      energy malnutrition.

PMID- 18037711
TI  - Psychiatric epidemiology in India.
AB  - Epidemiological studies report prevalence rates for psychiatric disorders from
      9.5 to 370/1000 populations in India. This review critically evaluates the
      prevalence rate of mental disorders as reported in Indian epidemiological
      studies. Extensive search of PubMed, NeuroMed and MEDLARS using search terms
      "psychiatry" and "epidemiology" was done. Manual search of literature was also
      done. Retrieved articles were systematically selected using inclusion and
      exclusion criteria. Only sixteen prevalence studies fulfilled the study criteria.
      Most of the epidemiological studies done in India neglected anxiety disorders,
      substance dependence disorders, co-morbidity and dual diagnosis. The use of poor
      sensitive screening instruments, single informant and systematic underreporting
      has added to the discrepancy in the prevalence rate. The prevalence of mental
      disorders reported in epidemiological surveys can be considered lower estimates
      rather than accurate reflections of the true prevalence in the population.
      Researchers have focused on broad non-specific, non-modifiable risk factors, such
      as age, gender and social class. Future research focused on the general
      population, longitudinal (prospective), multi-centre, co-morbid studies,
      assessment of disability, functioning, family burden and quality of life studies
      involving a clinical service providing approach, is required.

PMID- 18037712
TI  - High resolution CT (HRCT) in miliary tuberculosis (MTB) of the lung: Correlation
      with pulmonary function tests & gas exchange parameters in north Indian patients.
AB  - BACKGROUND & OBJECTIVE: High resolution computed tomography (HRCT) scans are
      known to be helpful in early diagnosis and management of patients with miliary
      tuberculosis (MTB). We made an attempt in this study to identify patterns of
      pulmonary MTB on HRCT and to correlate the HRCT disease extent with pulmonary
      function tests (PFT) and gas exchange analysis (GEA). METHODS: A total of 16 non
      HIV patients with MTB underwent HRCT of the chest, PFT and GEA. All the
      investigations in these patients were completed within 20 days of presentation.
      Evidence of TB was diagnosed by biopsy from lymph nodes (3/16), organ biopsy
      [skin, liver, bone marrow and lung (transbronchial) (6/16)]. In one patient
      fundoscopy revealed choroid tubercles. In 6 patients, diagnosis was confirmed by
      clinical/radiological improvement following anti-tuberculosis therapy.
      Radiological patterns of involvement on HRCT of the lungs were studied and
      disease extent was estimated in each case by consensus between two radiologists
      using specially devised visual scoring system. Disease extent was correlated with
      PFT and GEA. Spearman rank correlation was used for statistical analysis.
      RESULTS: Findings on HRCT in MTB included miliary nodularity (16/16), alveolar
      lesions such as ground glass attenuation and/or consolidation (5/16),
      lymphadenopathy (8/16), peribronchovascular interstitial thickening (1/16),
      emphysema (1/16), pleural pathology (2/16), and pericardial effusion (2/16). A
      significant correlation was noted between disease extent score and forced vital
      capacity (FVC) (r = -0.76; P=0.003), forced expiratory volume in one second
      (FEV(1))(r = -0.74; P = 0.005), total lung capacity (TLC) (r = -0.66; P = 0.037),
      oxygen saturation in arterial blood (SaO(2)) (r = -0.69, P = 0.01), diffusion
      capacity of the lung (DLco) (r = -0.8; P = 0.02). INTERPRETATION & CONCLUSION:
      Our findings showed that HRCT reliably diagnosed MTB, and thus could help in
      predicting derangement of pulmonary function tests and GEA in these patients.

PMID- 18037713
TI  - A pilot study on the effects of curd (dahi) & leaf protein concentrate in
      children with protein energy malnutrition (PEM).
AB  - BACKGROUND & OBJECTIVE: In protein-energy malnutrition (PEM) there is a
      significant impairment of immunity, both cell-mediated and humoral, which may be
      reversed with nutritional rehabilitation. With the use of probiotics like curd
      (dahi) and micronutrient-rich leaf protein concentrate (LPC), this immune
      recovery may be hastened. This study was conducted to assess the impact of
      supplementation of curd and LPC on nutritional status, and immunity as assessed
      by anthropometry, haemoglobin, ferritin levels, T- cell subpopulation and C
      reactive protein (CRP), in children suffering from PEM. METHODS: Eighty moderate
      to severely malnourished children (1-5 yr) were randomized to receive either curd
      or LPC in addition to WHO recommended two-step diet over 15 days. Nutritional,
      immunological and haematological parameters were measured before and after
      supplementation and compared within the groups. RESULTS: The change in weight,
      haemoglobin level and CD4:CD8 T-cell subpopulation was significant in both the
      groups after supplementation. Response of CRP was blunted in PEM. Serum ferritin
      decreased significantly after supplementation in both groups. INTERPRETATION &
      CONCLUSION: Curd and LPC when added to diet of malnourished children, may have
      therapeutic value by accelerating immune recovery. More studies need to be done
      on a larger sample to confirm these findings.

PMID- 18037714
TI  - Level of oxidative stress in the red blood cells of patients with liver
      cirrhosis.
AB  - BACKGROUND & OBJECTIVE: Liver cirrhosis is associated with gastrointestinal
      haemorrhage and oesophageal variceal bleeding. Altered platelet functions has
      been reported to be a cause of bleeding complication. We carried out this study
      to find out the level of oxidative stress in the red blood cells of patients with
      liver cirrhosis. METHODS: Fifty patients admitted with the complication of liver
      cirrhosis (with bleeding complications, n=30 and without bleeding complications,
      n=20) were included in the study. Age and sex matched normal healthy volunteers
      (n=45) served as controls. The levels of oxyhaemoglobin and methaemoglobin were
      assayed in the red blood cells. Oxidative stress markers such as lipid peroxides,
      lipid hydroperoxides and nitric oxide were determined along with enzymatic
      antioxidants. Membrane bound adenosine triphosphatases, cytosolic glucose-6
      phosphate dehydrogenase and NADHmethaemoglobin reductase were also measured. The
      levels of cholesterol and total phospholipids were assessed in red blood cell
      membrane. The osmotic fragility of red blood cells was monitored using different
      concentrations of sodium chloride. RESULTS: The level of methaemoglobin was
      significantly higher (P < 0.001) in the red blood cells of liver cirrhotic
      patients with bleeding complication compared to that of non bleeding patients.
      The activity level of NADH-methaemoglobin reductase was significantly lower
      (P<0.001) compared to that of normal subjects. Levels of oxidative stress markers
      including nitric oxide were found to be higher in patients. The levels of
      enzymatic antioxidants were low except of glutathione peroxidase. The activity
      levels of adenosine triphosphatases were also found to be significantly lower
      (P<0.001) in patients compared to normal subjects. A significant alteration
      (P<0.05) was found in membrane cholesterol/phospholipid ratio of cirrhotic
      bleeders. Osmotic fragility of red blood cells was also altered in patients.
      INTERPRETATION & CONCLUSION: In cirrhotic condition red blood cells are subjected
      to severe oxidative stress with significant alterations in the membrane
      properties.

PMID- 18037715
TI  - Prevalence & risk factors for hepatitis C virus among pregnant women.
AB  - BACKGROUND & OBJECTIVE: Information on hepatitis C virus (HCV) infection in
      pregnant women in India is scanty. This study was carried out to investigate the
      prevalence of HCV within an obstetric population in north India and to identify
      the various risk factors for the viral infection. METHODS: A total of 8130
      pregnant women from antenatal clinic were subjected to anti-HCV testing by third
      generation ELISA. Anti-HCV positive seropositive women were further tested for
      HCVRNA, hepatitis B and HIV. The women were evaluated for the presence of
      following known risk factors for HCV infection. RESULTS: Eighty four (1.03%)
      pregnant females had HCV antibodies. Of these, 46 (54.8%) were positive for HCV
      RNA, 4(4.8%) tested positive for HBsAg, while none tested positive for HIV. The
      mean age and parity of the anti-HCV antibody positive women was 24.36+/-3.6 yr
      and 0.9+/-0.8, while that of the anti-HCV antibody negative women was 24.13+/-3.6
      yr and 0.8+/-0.8 respectively. Of the 84 anti-HCV positive women, 52 (61.9 %) did
      not have any identifiable risk factors. The risk factors variables did not have
      significant association with HCV positive status. INTERPRETATION & CONCLUSION:
      Prevalence of hepatitis C in pregnant women was 1.03 per cent. None of the known
      risk factors was found to be significantly associated with the HCV infection.
      Hence case identification and consequent management pose a particular problem and
      routine screening is not a viable option in our resource- poor setting.

PMID- 18037716
TI  - Prevalence & susceptibility to fluconazole of Candida species causing
      vulvovaginitis.
AB  - BACKGROUND & OBJECTIVE: Vulvovaginal candidiasis is an important cause of
      morbidity in women of reproductive age. This study was carried out to determine
      the species prevalence and susceptibility pattern to fluconazole of yeasts
      isolated from the vagina of symptomatic women. METHODS: This prospective study
      was conducted in a rural primary health care center of north India from May 2003
      to April 2004 and included 601 married, sexually active women (18-49 yr) with the
      self reported symptoms of vaginal discharge and/or genital itching and/or genital
      burning. Specific aetiology of the genitourinary symptoms including candidal
      infection were determined. Specimens from the lateral wall of vagina were
      subjected to direct wet mount microscopy and fungal culture on Sabouraud's
      dextrose agar. Susceptibility testing to fluconazole was carried out using broth
      microdilution method. RESULTS: Yeasts were isolated in 111 (18.5%) women and
      these consisted of Candida glabrata (56, 50.4%), C. albicans (39, 35.1%), C.
      tropicalis (12, 10.8%), C. krusei (3, 2.7%) and C. parapsilosis (1, 0.9%).
      Susceptibility testing carried out on 30 representative isolates (15 C. glabrata,
      10 C. albicans, 4 C. tropicalis and 1 C. parapsilosis) revealed that 21 isolates
      (70%) were susceptible (MIC, < or = 8 microg/ml) to fluconazole while 9 (30%)
      were susceptible-dose dependent (S-DD, MIC 16-32 microg/ml). INTERPRETATION &
      CONCLUSION: Our findings suggest a low prevalence of fluconazole resistance in
      vaginal candida isolates in our population. However, a high prevalence of non
      albicans candida species and increased dose-dependent resistance in these
      isolates necessitates vigilance since this may warrant a change in the optimal
      therapy of non-albicans candida vaginitis.

PMID- 18037717
TI  - Detection of Amp C beta lactamases production in Escherichia coli & Klebsiella by
      an inhibitor based method.
AB  - BACKGROUND & OBJECTIVE: Detection of AmpC-mediated resistance in Gram-negative
      organisms poses a problem due to misleading results in phenotypic tests. There
      are no recommended guidelines for detection of this resistance mechanism and
      there is a need to address this issue as much as the detection of extended
      spectrum beta lactamases (ESBLs) since both may co-exist and mask each other.
      Though resistance to cefoxitin is used as a screening test, it does not reliably
      indicate Amp C production. This study was undertaken to detect Amp C beta
      lactamases in certain Gram-negative bacteria employing an inhibitor base test
      using boronic acid. METHODS: A total number of 76 consecutive non repetitive
      clinical isolates of Escherichia coli (n=67) and 9 Klebsiella pneumoniae (n=9)
      obtained over a period of two months, were screened for amp C production by disc
      diffusion method using cefoxitin (30 microg) dics and confirmed by inhibitor
      based test using boronic acid as inhibitor. RESULTS: A total of 36 of 76 isolates
      (47.3%) screened harboured amp C enzymes, of which a majority 31 (86.1%) co
      produced ESBL enzymes. Pure ampC production was seen in 7 (9.2%) of isolates
      only. INTERPRETATION & CONCLUSION: Most of the amp C producers also produced ESBL
      enzymes. The inhibitor based test was useful in identifying cefoxitin susceptible
      amp C producers and could also effectively differenciate ESBL from amp C
      producing isolates.

PMID- 18037718
TI  - Glycaemic evaluation of Psidium guajava in rats.
AB  - BACKGROUND & OBJECTIVE: Many plant polysaccharides exhibit hypoglycaemic effect.
      Though the fruit of Psidium guajava is known to contain free sugars, the fruit
      extract showed hypoglycaemic effect in alloxan treated mice and human subjects.
      The present study was aimed to determine the glycaemic potential of P. guajava
      fruit peel extract on blood glucose level (BGL) of normal and
      streptozotocininduced sub-diabetic rats during fasting blood glucose (FBG) and
      glucose tolerance test (GTT). METHODS: Female albino Wistar rats (n=42) were
      divided into seven equal groups, and were given different doses of fruit peel
      extract. Diabetes was induced by streptozotocin injection (ip) at a dose of 45
      mg/kg body weight. Blood glucose levels were measured after collecting the blood
      from tail veins. RESULTS: The diabetic and sub-diabetic models showed
      hyperglycaemic effect from a single oral administration of variable doses of P.
      guajava fruit peel extract. The maximum rise of 26.51 per cent was observed in
      BGL from a dose of 400 mg/kg bw exactly after 8 h of administration in normal
      rats whereas the maximum rise of 90.7 per cent was observed with the same dose of
      400 mg/kg bw after 2 h of glucose administration in sub-diabetic rats.
      INTERPRETATION & CONCLUSION: The hyperglycaemic effect of P. guajava fruit peel
      suggests that the diabetic patients should peel off the guava fruits before
      consuming. However, it can also be useful in controlling hypoglycaemia
      occasionally caused due to excess of insulin and other hypoglycaemic drugs.

PMID- 18037719
TI  - Effect of storage temperature on cholesterol measurement from dried blood.

PMID- 18037720
TI  - Pathogenic rapidly growing: Mycobacterium manitobense in the environment of Agra,
      north India.

PMID- 18037721
TI  - Insects did it first: a micropatterned adhesive tape for robotic applications.
AB  - Based on the structural and experimental studies of more than 300 insect species
      from different lineages, we have developed and characterized a bioinspired
      polymer material with the ability of multiple glue-free bonding and debonding.
      The material surface is covered with a pattern of microstructures, which
      resembles the geometry of tenent hairs previously described from the feet of
      flies, beetles, earwigs and other insects. The tape with such a microstructure
      pattern demonstrates at least two times higher pull-off force per unit apparent
      contact area compared to the flat polymer. Additionally, the tape is less
      sensitive to contamination by dust particles than a commercially available
      pressure-sensitive adhesive tape. Even if the 'insect tape' is contaminated, it
      can be washed with a soap solution in water, in order to completely recover its
      adhesive properties. We have successfully applied the tape to the 120 g wall
      climbing robot Mini-Whegs. Furthermore, the tape can be used for multiple
      adhering of objects to glass surfaces or as a protective tape for sensitive glass
      surfaces of optical quality. Another area of potential applications is gripping
      and manipulation of objects with smooth surfaces.

PMID- 18037722
TI  - The dream of staying clean: Lotus and biomimetic surfaces.
AB  - The Lotus has been the symbol of purity for thousands of years; contaminations
      and pathogens are washed off the surfaces of Lotus and some other plants with
      rain or even dew. After the introduction of scanning electron microscopy, we were
      able to resolve the mechanism behind this phenomenon. It took some further
      decades before in-depth studies on self-cleaning with plants were conducted and
      the effect could be understood in detail. We identified extreme water-repellency
      ('superhydrophobicity'), characterized by very high contact angles and low
      sliding angles, as the prerequisite for self-cleaning properties. We could show
      that the combination of two factors is necessary for obtaining a high degree of
      water-repellency: (1) low energy surfaces being hydrophobic and (2) surface
      structures that significantly increase hydrophobicity. It is suggested that this
      mechanism plays an important role in the protection of plants against pathogens.
      Our technological application of this effect has resulted in the development of
      successful, eco-friendly and sustainable industrial products. Another interesting
      property was found with superhydrophobic surfaces of certain aquatic and semi
      aquatic plants and animals: here a layer of air under water is retained. We
      present a new approach of using this feature for creating structured, air
      retaining surfaces for technical underwater applications. It is proposed that
      such surfaces can reduce significantly the drag of large ships. We conclude that
      basic biological research is of particular importance for true innovation. Our
      research on superhydrophobic self-cleaning biological surfaces and the
      development of similar engineered materials suggests that biomimicry is a matter
      of multi-stage processes rather than a simple copying of biological developments.

PMID- 18037723
TI  - Using hardware models to quantify sensory data acquisition across the rat
      vibrissal array.
AB  - Our laboratory investigates how animals acquire sensory data to understand the
      neural computations that permit complex sensorimotor behaviors. We use the rat
      whisker system as a model to study active tactile sensing; our aim is to
      quantitatively describe the spatiotemporal structure of incoming sensory
      information to place constraints on subsequent neural encoding and processing. In
      the first part of this paper we describe the steps in the development of a
      hardware model (a 'sensobot') of the rat whisker array that can perform object
      feature extraction. We show how this model provides insights into the
      neurophysiology and behavior of the real animal. In the second part of this
      paper, we suggest that sensory data acquisition across the whisker array can be
      quantified using the complete derivative. We use the example of wall-following
      behavior to illustrate that computing the appropriate spatial gradients across a
      sensor array would enable an animal or mobile robot to predict the sensory data
      that will be acquired at the next time step.

PMID- 18037724
TI  - Biosonar-inspired technology: goals, challenges and insights.
AB  - Bioinspired engineering based on biosonar systems in nature is reviewed and
      discussed in terms of the merits of different approaches and their results:
      biosonar systems are attractive technological paragons because of their
      capabilities, built-in task-specific knowledge, intelligent system integration
      and diversity. Insights from the diverse set of sensing tasks solved by bats are
      relevant to a wide range of application areas such as sonar, biomedical
      ultrasound, non-destructive testing, sensors for autonomous systems and wireless
      communication. Challenges in the design of bioinspired sonar systems are posed by
      transducer performance, actuation for sensor mobility, design, actuation and
      integration of beamforming baffle shapes, echo encoding for signal processing,
      estimation algorithms and their implementations, as well as system integration
      and feedback control. The discussed examples of experimental systems have
      capabilities that include localization and tracking using binaural and multiple
      band hearing as well as self-generated dynamic cues, classification of small
      deterministic and large random targets, beamforming with bioinspired baffle
      shapes, neuromorphic spike processing, artifact rejection in sonar maps and
      passing range estimation. In future research, bioinspired engineering could
      capitalize on some of its strengths to serve as a model system for basic
      automation methodologies for the bioinspired engineering process.

PMID- 18037725
TI  - Micromachined biomimetic artificial haircell sensors.
AB  - The biological haircell is a modular building block of a rich variety of
      biological sensors. Using micro- and nanofabrication technology, an engineering
      equivalent artificial haircell sensor can be developed, imitating the structure
      and transfer function of the biological haircell. The artificial haircells can be
      made of hybrid semiconductor, metal and polymers. This paper discusses a number
      of strategies, using representative material systems, for building artificial
      haircell sensors and briefly outlines their fabrication method and performance.
      The motivation for imitating the biological haircell is also discussed to provide
      a background for this work.

PMID- 18037726
TI  - Inspiration, simulation and design for smart robot manipulators from the sucker
      actuation mechanism of cephalopods.
AB  - Octopus arms house 200-300 independently controlled suckers that can alternately
      afford an octopus fine manipulation of small objects and produce high adhesion
      forces on virtually any non-porous surface. Octopuses use their suckers to grasp,
      rotate and reposition soft objects (e.g., octopus eggs) without damaging them and
      to provide strong, reversible adhesion forces to anchor the octopus to hard
      substrates (e.g., rock) during wave surge. The biological 'design' of the sucker
      system is understood to be divided anatomically into three functional groups: the
      infundibulum that produces a surface seal that conforms to arbitrary surface
      geometry; the acetabulum that generates negative pressures for adhesion; and the
      extrinsic muscles that allow adhered surfaces to be rotated relative to the arm.
      The effector underlying these abilities is the muscular hydrostat. Guided by
      sensory input, the thousands of muscle fibers within the muscular hydrostats of
      the sucker act in coordination to provide stiffness or force when and where
      needed. The mechanical malleability of octopus suckers, the interdigitated
      arrangement of their muscle fibers and the flexible interconnections of its parts
      make direct studies of their control challenging. We developed a dynamic
      simulator (ABSAMS) that models the general functioning of muscular hydrostat
      systems built from assemblies of biologically constrained muscular hydrostat
      models. We report here on simulation studies of octopus-inspired and artificial
      suckers implemented in this system. These simulations reproduce aspects of
      octopus sucker performance and squid tentacle extension. Simulations run with
      these models using parameters from man-made actuators and materials can serve as
      tools for designing soft robotic implementations of man-made artificial suckers
      and soft manipulators.

PMID- 18037727
TI  - From honeybees to Internet servers: biomimicry for distributed management of
      Internet hosting centers.
AB  - An Internet hosting center hosts services on its server ensemble. The center must
      allocate servers dynamically amongst services to maximize revenue earned from
      hosting fees. The finite server ensemble, unpredictable request arrival behavior
      and server reallocation cost make server allocation optimization difficult.
      Server allocation closely resembles honeybee forager allocation amongst flower
      patches to optimize nectar influx. The resemblance inspires a honeybee biomimetic
      algorithm. This paper describes details of the honeybee self-organizing model in
      terms of information flow and feedback, analyzes the homology between the two
      problems and derives the resulting biomimetic algorithm for hosting centers. The
      algorithm is assessed for effectiveness and adaptiveness by comparative testing
      against benchmark and conventional algorithms. Computational results indicate
      that the new algorithm is highly adaptive to widely varying external environments
      and quite competitive against benchmark assessment algorithms. Other swarm
      intelligence applications are briefly surveyed, and some general speculations are
      offered regarding their various degrees of success.

PMID- 18037728
TI  - Training mechanical engineering students to utilize biological inspiration during
      product development.
AB  - The use of bio-inspiration for the development of new products and devices
      requires new educational tools for students consisting of appropriate design and
      manufacturing technologies, as well as curriculum. At the University of Maryland,
      new educational tools have been developed that introduce bio-inspired product
      realization to undergraduate mechanical engineering students. These tools include
      the development of a bio-inspired design repository, a concurrent fabrication and
      assembly manufacturing technology, a series of undergraduate curriculum modules
      and a new senior elective in the bio-inspired robotics area. This paper first
      presents an overview of the two new design and manufacturing technologies that
      enable students to realize bio-inspired products, and describes how these
      technologies are integrated into the undergraduate educational experience. Then,
      the undergraduate curriculum modules are presented, which provide students with
      the fundamental design and manufacturing principles needed to support bio
      inspired product and device development. Finally, an elective bio-inspired
      robotics project course is present, which provides undergraduates with the
      opportunity to demonstrate the application of the knowledge acquired through the
      curriculum modules in their senior year using the new design and manufacturing
      technologies.

PMID- 18037729
TI  - The bombardier beetle and its use of a pressure relief valve system to deliver a
      periodic pulsed spray.
AB  - In this paper the combustion chamber of the bombardier beetle is considered and
      recent findings are presented which demonstrate that certain parts of the anatomy
      are in fact inlet and outlet valves. In particular, the authors show that the
      intake and exhaust valve mechanism involves a repeated (pulsating) steam
      explosion, the principle of which was up till now unclear. New research here has
      now shown the characteristics of the ejections and the role of important valves.
      In this paper numerical simulations of the two-phase flow ejection are presented
      which demonstrate that the principle of cyclic water injection followed by water
      and steam decompression explosions is the fundamental mechanism used to create
      the repeated ejections.

PMID- 18037730
TI  - Artificial evolution of the morphology and kinematics in a flapping-wing mini
      UAV.
AB  - Birds demonstrate that flapping-wing flight (FWF) is a versatile flight mode,
      compatible with hovering, forward flight and gliding to save energy. This
      extended flight domain would be especially useful on mini-UAVs. However, design
      is challenging because aerodynamic efficiency is conditioned by complex movements
      of the wings, and because many interactions exist between morphological (wing
      area, aspect ratio) and kinematic parameters (flapping frequency, stroke
      amplitude, wing unfolding). Here we used artificial evolution to optimize these
      morpho-kinematic features on a simulated 1 kg UAV, equipped with wings
      articulated at the shoulder and wrist. Flight tests were conducted in a dedicated
      steady aerodynamics simulator. Parameters generating horizontal flight for
      minimal mechanical power were retained. Results showed that flight at medium
      speed (10-12 m s(-1)) can be obtained for reasonable mechanical power (20 W kg(
      1)), while flight at higher speed (16-20 m s(-1)) implied increased power (30-50
      W kg(-1)). Flight at low speed (6-8 m s(-1)) necessitated unrealistic power
      levels (70-500 W kg(-1)), probably because our simulator neglected unsteady
      aerodynamics. The underlying adaptation of morphology and kinematics to varying
      flight speed were compared to available biological data on the flight of birds.

PMID- 18037731
TI  - Anthocyanins from red flowers of Camellia reticulata LINDL.
AB  - Ten anthocyanins, cyanidin 3-sambubioside, 3-glucoside and their acylated
      derivatives, cyanidin 3-lathyroside and cyanidin 3-galactoside, were isolated
      from red flowers of Camellia reticulata. Their structures were determined on the
      basis of spectroscopic analyses, and the chemotaxonomic distribution of the
      accumulated anthocyanins in the petals of wild Camellia reticulata and C.
      pitardii var. yunnanica is discussed.

PMID- 18037732
TI  - Effects of medication on cardiovascular events in the Japanese coronary artery
      disease (JCAD) study.
AB  - BACKGROUND: Actual data regarding coronary artery disease (CAD) patients in Japan
      is scarce, so in the present study a large database of Japanese patients with
      significant CAD was constructed for analysis of the relationship between medical
      treatments and outcomes in this cohort. METHODS AND RESULTS: The present study
      enrolled 15,628 patients who underwent coronary angiography and were diagnosed as
      having significant stenosis in at least 1 coronary artery. Of these, 13,812
      patients were followed up and included in the analysis: 10,626 (77%) men and
      3,186 (23%) women. Diagnosis at the time of registration was acute myocardial
      infarction (AMI) for 2,955 patients, old myocardial infarction for 3,913 patients
      and unstable angina pectoris for 2,049 patients. Patients were followed up for an
      average of 2.7 years. At the start of the follow-up, 37.4% of the patients were
      prescribed statins, 50.2% calcium-channel blockers (CCB), 31.6% angiotensin
      converting enzyme inhibitors (ACEI), 13.5% angiotensin II receptor blockers (ARB)
      and 60.2% nitrates. Univariate Cox regression model analysis showed that the
      hazard ratio (HR) of statins was 0.780 (95% confidence intervals (CI), 0.710
      0.856; p<0.001); fibrates, 0.580 (95%CI, 0.425-0.790; p=0.001); CCB, 1.067
      (95%CI, 0.976-1.166; p=0.153); ACEI, 1.062 (95%CI, 0.968-1.166; p=0.202); ARB,
      1.036 (95%CI, 0.914-1.174; p=0.581); nitrates, 1.147 (95%CI, 1.043-1.260;
      p=0.005). When the data were adjusted for background data and all cardiovascular
      medications, the HR of statins was 0.809 (95%CI, 0.726-0.901; p<0.001), CCB 1.031
      (95%CI, 0.937-1.135; p=0.535), ACEI 1.023 (95%CI, 0.924-1.132; p=0.663), ARB
      0.991 (95%CI, 0.867-1.132; p=0.890), nitrates 1.074 (95%CI, 0.973-1.186;
      p=0.155). For patients presenting with AMI at the time of registration, the HR of
      CCB was 1.340 (95%CI, 1.084-1.655; p=0.007) and that of nitrates was 0.862
      (95%CI, 0.703-1.059; p=0.157). CONCLUSION: In a cohort of CAD patients in Japan,
      the prescription pattern differed from that of Western studies. Statins and
      fibrates were shown to be significantly beneficial in the whole cohort. In the
      AMI subgroup, CCB showed a deleterious effect and nitrates showed a non
      significant tendency for beneficial effect, which should be investigated in
      future randomized control trials.

PMID- 18037733
TI  - Weekend onset of acute myocardial infarction does not have a negative impact on
      outcome in Japan.
AB  - BACKGROUND: Studies from North America indicate that patients admitted during the
      weekend with acute myocardial infarction (AMI) have a worse outcome than weekday
      admitted patients, probably reflecting a lower rate of invasive procedures.
      However, it is unclear whether the same is true in Japan, which has a different
      healthcare system. METHODS AND RESULTS: Using the Japanese Acute Coronary
      Syndrome Study (JACSS) database, this study included 4,805 consecutive patients
      who were admitted within 48 h of onset of AMI (3,526 [73.4%] patients with
      weekday onset [Monday through Friday] and 1,279 [26.6%] with weekend onset
      [Saturday and Sunday]). There were no significant differences between the 2
      groups in patient background and clinical features. The proportions of patients
      who underwent emergency catheterization (88.4% vs 88.0%) and reperfusion therapy
      (81.5% vs 81.4%) were also similar. There were no differences between the 2
      groups in the in-hospital, 30-day, and 1-year mortality rates. Even after various
      adjustments, there was no difference in the risk of death associated with weekend
      versus weekday onset of AMI. CONCLUSION: There were no obvious differences in
      outcome for Japanese AMI patients in the weekday- or weekend-onset group,
      suggesting the quality of the Japanese healthcare system is similar for the
      entire week.

PMID- 18037734
TI  - Randomized evaluation of atorvastatin in patients with coronary heart disease: a
      serial intravascular ultrasound study.
AB  - BACKGROUND: It is unclear whether a marked reduction of low-density lipoprotein
      cholesterol (LDL-C) in patients with coronary heart disease (CHD) and mild
      hypercholesterolemia leads to less progression of atherosclerosis. METHODS AND
      RESULTS: Patients with CHD and hypercholesterolemia (100<LDL-C<140 mg/dl) who
      underwent coronary angiography (CAG) and intravascular ultrasound (IVUS) were
      randomly assigned to the atorvastatin (10-20 mg/day) group or ;usual care' group.
      After 12 months 58 patients had follow-up CAG and IVUS studies that could be
      evaluated. Cross-sectional areas of the vessel, lumen, and plaque were measured
      at 1-mm intervals, and volumetric calculations were based on Simpson's rule.
      After 12 months, the mean reduction of LDL-C was 34% in the atorvastatin group
      and 0% in the usual care group (p<0.01). The mean absolute plaque volume showed a
      larger increase in the usual care group than in the atorvastatin group
      (atorvastatin -1.4+/-11.6 mm3, usual care 7.6+/-10.3 mm3; p<0.01). Vessel volume
      also showed a larger increase in the usual care group than in the atorvastatin
      group (atorvastatin 2.2+/-10.9 mm3, usual care 10.9+/-17.7 mm3; p=0.03).
      CONCLUSIONS: Atorvastatin treatment prevented the further progression of
      atherosclerosis by maintaining LDL-C below 100 mg/dl in patients with CHD and
      hypercholesterolemia (100<LDL-C<140 mg/dl).

PMID- 18037735
TI  - Lack of ST-segment depression normalization after PCI is a predictor of 5-year
      mortality in patients with ST-elevation myocardial infarction.
AB  - BACKGROUND: The significance of dynamic changes in a depressed ST-segment in the
      reciprocal changes after percutaneous coronary intervention (PCI) of patients
      with ST-elevation myocardial infarction (STEMI) is unknown, so the aim of this
      study was to evaluate the significance of reciprocal ST-segment depression
      normalization (STN) on long-term mortality in patients with STEMI treated with
      primary PCI. METHODS AND RESULTS: Data for 247 consecutive patients with STEMI
      were analyzed; 84 patients were excluded because of exclusion or incomplete
      inclusion criteria, so finally, 163 patients successfully treated with primary
      PCI were included. The study group was divided into 3 subgroups according to
      percentage of STN: poor STN (<30%), partial STN (30-70%), complete STN (>70%).
      Complete STN occurred in 63%, partial in 24% and poor in 13% of patients. STN
      correlated with late mortality (15% vs 28% vs 38% respectively, p=0.012).
      Patients who died during the follow-up period had a lower mean percentage
      reduction of initial ST-segment depression after PCI (50% vs 75%, p=0.001).
      Percentage reduction of initial ST-segment depression after PCI was a significant
      and independent risk factor of long-term mortality (odds ratio 1.01; 95%
      confidence interval: 1.00-1.02; p=0.02). CONCLUSIONS: These data revealed the use
      of reciprocal changes normalization as a novel tool for assessment of long-term
      risk of death in patients after successful primary PCI for STEMI.

PMID- 18037736
TI  - Association between circulating level of CD40 ligand and angiographic morphologic
      features indicating high-burden thrombus formation in patients with acute
      myocardial infarction undergoing primary coronary intervention.
AB  - BACKGROUND: This study tested the hypothesis that in the acute phase of
      myocardial infarction (MI), the circulating level of soluble CD40 ligand
      (sCD40L), an index of platelet activation, is predictive of angiographic
      morphologic features that indicate high-burden thrombus formation (HBTF) in the
      infarct-related artery (IRA). METHODS AND RESULTS: This prospective study
      included 162 consecutive patients: 64 with HBTF and 98 with low-burden thrombus
      formation (LBTF). All patients had a Killip's classification<or=3 ST-segment
      elevation acute myocardial infarction (AMI) of onset<12 h who were undergoing
      primary percutaneous coronary intervention (PCI). Blood samples for measurement
      of the circulating levels of sCD4L and high-sensitivity C-reactive protein (hs
      CRP) and white blood cell (WBC) count were collected before PCI. The circulating
      levels of sCD40L and hs-CRP, and the WBC count were also evaluated in 20 normal
      control subjects. Blood was aspirated by export suction catheter from the
      intracoronary artery (ICA) in 49 HBTF patients. The WBC count, and the
      circulating levels of hs-CRP and sCD40L were significantly higher in the HBTF and
      LBTF groups than in the normal control subjects (all p<0.005). Additionally, the
      circulating levels of sCD40L and the WBC count were substantially higher in the
      HBTF than in the LBTF patients (all p<0.001). Furthermore, in HBTF patients the
      ICA had a significantly higher sCD40L level and WBC count compared with the
      values for the systemic circulation (all p<0.001). Multiple statistical analyses
      identified increased circulating level of sCD40L as the most independent
      predictor of HBTF in the IRA (p<0.0001). CONCLUSIONS: The sCD40L level is the
      most independent predictor of angiographic morphologic features that indicate
      HBTF in the acute phase of MI.

PMID- 18037737
TI  - Clinical results of coronary revascularization in left ventricular dysfunction.
AB  - BACKGROUND: In the present study 15 years of experience with surgical coronary
      artery bypass grafting (CABG) in patients with left ventricular (LV) dysfunction
      were retrospectively analyzed. METHODS AND RESULTS: Between August 1990 and May
      2005, a total of 120 patients with severe LV dysfunction (LV ejection fraction
      (EF)<or=30%) caused by coronary artery disease underwent CABG (mean age 60.3
      years, 94 males) Among the 120 patients, 102 had 3-vessel or left main disease.
      Mean LVEF was 23.5%, and 75% of patients were New York Heart Association
      functional class III or IV. CABG was performed in all patients with a mean of 2.9
      distal grafts/patient. There were 13 hospital deaths (11%). Mean LVEF improved to
      32% postoperatively, and further improved to 39% at a mean follow-up of 57.6
      months (p<0.05). During the follow-up period, 2 cardiac-related deaths occurred.
      Kaplan-Meier survival rates at 1, 5 and 10 years were 87.7%, 80.9%, and 44.4%,
      respectively, and respective freedom from cardiac-related event rates were 96.5%,
      90.3% and 63.5%. CONCLUSIONS: CABG in patients with severe LV dysfunction
      provides optimal survival with an improved EF and functional state, and may
      provide a good alternative to transplantation in selected patients.

PMID- 18037738
TI  - Cilostazol could ameliorate platelet responsiveness to clopidogrel in patients
      undergoing primary percutaneous coronary intervention.
AB  - BACKGROUND: Cilostazol increases the cyclic adenosine monophosphate levels in
      platelets and might ameliorate the antiplatelet activity of clopidogrel. This
      study investigated the additional effect of cilostazol on platelet aggregation
      measured by a VerifyNow analyzer and soluble CD40 ligand (sCD40L) as a marker of
      activated platelet in patients undergoing primary percutaneous coronary
      intervention (PCI). METHODS AND RESULTS: Sixty cases of primary PCI were randomly
      assigned to dual (aspirin and clopidogrel) or triple (dual plus cilostazol)
      therapy. The antiplatelet effects of aspirin and clopidogrel were evaluated by
      VerifyNow tests. The plasma sCD40L levels at admission, 24 h and 21 days were
      measured by the ELISA method. The arachidonic acid induced platelet aggregation
      was similar in both groups. However, the triple group had a significantly lower
      P2Y12 reaction unit (dual 208.8+/-69.0 vs triple 168.2+/-79.2, p=0.041) and
      higher % inhibition of adenosine diphosphate (ADP)-induced platelet aggregation
      (dual 23.8+/-21.4% vs triple 40.5+/-21.0%, p=0.004). In the multivariate
      analysis, cilostazol was a negative predictor for low responders to clopidogrel
      (95% confidence interval 0.067-0.711). The plasma sCD40L levels were not
      significantly different between the 2 groups at the same point of time.
      CONCLUSIONS: The addition of cilostazol to the combination of aspirin plus
      clopidogrel significantly increases the inhibition of ADP-induced platelet
      aggregation. However, there was no additive effect on aspirin-induced
      antiplatelet activity or lowering of sCD40L.

PMID- 18037739
TI  - Direct comparison of transcardiac increase in brain natriuretic peptide (BNP) and
      N-terminal proBNP and prognosis in patients with chronic heart failure.
AB  - BACKGROUND: No previous study has compared the transcardiac gradient of cardiac
      natriuretic peptides and prognosis. METHODS AND RESULTS: To compare the
      prognostic value of the transcardiac increase in brain natriuretic peptide (BNP)
      and N-terminal proBNP (NT-proBNP) in patients with chronic heart failure (CHF),
      the hemodynamic parameters and plasma levels of BNP and NT-proBNP were measured
      in the aortic root (AO) and coronary sinus (CS) in 353 consecutive patients with
      CHF. During a median follow-up of 2.8 years, 35 patients died. The molar ratio of
      (CS-AO) NT-proBNP to (CS-AO) BNP correlated with hemodynamic abnormalities and it
      was significantly higher in non-survivors than in survivors (median value=0.702
      vs 0.437, respectively; p=0.0009), suggesting that NT-proBNP is superior to BNP
      in terms of transcardiac increase. After adjustment for clinical variables
      associated with CHF, including hemodynamics and an estimated glomerular
      filtration rate, it was found that only the plasma NT-proBNP level was an
      independent prognostic predictor, even after considering the transcardiac
      increases in BNP and NT-proBNP. CONCLUSION: These findings suggest that the
      transcardiac gradient of NT-proBNP to BNP molar ratio increases with the severity
      of left ventricular dysfunction, and that plasma NT-proBNP level may be more
      useful than BNP for evaluating the prognosis of patients with CHF.

PMID- 18037740
TI  - Osteopontin expression of circulating T cells and plasma osteopontin levels are
      increased in relation to severity of heart failure.
AB  - BACKGROUND: T cells in peripheral blood reflect the systemic inflammatory
      response in patients with heart failure (HF). In a rat model of HF, osteopontin
      is dramatically increased in the left ventricular myocardium, so the association
      between osteopontin and HF was examined in the present study. METHODS AND
      RESULTS: Peripheral blood was collected from 93 patients with heart disease and
      38 controls. Left ventricular ejection fraction (LVEF) was calculated using a
      modified Simpson's rule. The 93 patients were classified into 3 classes according
      to the New York Heart Association (NYHA) functional classification. Osteopontin
      expressing CD4+ T cells were quantified by flow cytometry. Plasma osteopontin
      levels (ng/ml) and the frequencies of osteopontin-expressing CD4+ T cells (%)
      were higher in patients with HF than in controls (800+/-554, 575+/-229, p=0.016
      and 27.3+/-12.2, 16.7+/-10.0, p<0.001). Furthermore, the plasma osteopontin
      levels and the frequencies of osteopontin-expressing CD4+ T cells increased in
      proportion to the severity of the NYHA functional class. The frequencies of
      osteopontin-expressing CD4+ T cells were significantly correlated with LVEF (r=
      0.336, p=0.0048) and log plasma brain natriuretic peptide levels (r=0.305,
      p=0.0025). CONCLUSIONS: Osteopontin expression of circulating CD4+ T cells and
      plasma osteopontin levels reflect the severity of HF. Osteopontin could be a new
      target in the assessment of HF.

PMID- 18037741
TI  - Activity monitoring in heart failure patients with cardiac resynchronization
      therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves functional capacity
      in heart failure patients. This study aimed to prospectively analyze long-term
      device-based monitoring of physical activity in patients undergoing CRT. METHODS
      AND RESULTS: The Activity Log Index (ALI), calculated by CRT devices, represents
      the percentage of time when acceleration exceeds a threshold and monitors the
      physical activity. Data from 178 CRT patients (New York Heart Association III
      91%, left ventricular ejection fraction 21+/-6%, left ventricular end-diastolic
      diameter 69+/-9 mm, QRS 159+/-27 ms, sinus rhythm 81%) were retrieved. The ALI
      increased from a baseline value of 3.6+/-2.0 to 11.2+/-4.6 (p<0.005) 104 weeks
      after initiation of CRT. A plateau was reached at approximately 12 weeks and
      thereafter ALI remained stable for up to 2 years. The magnitude of the changes in
      ALI was similar in patients with different etiologies and underlying rhythms.
      Despite similar values at baseline, elderly patients (>or=65 years) exhibited
      significantly lower ALI values than younger patients during the follow-up and at
      the plateau (9.5+/-4.2 vs 13.3+/-4.8, p<0.001). CONCLUSIONS: Device-based
      monitoring of physical activity in CRT patients is feasible. CRT resulted in a
      large and long-term increase in physical activity.

PMID- 18037742
TI  - Transient enhancement of oxidant stress and collagen turnover in patients with
      acute worsening of congestive heart failure.
AB  - BACKGROUND: Myocardial remodeling is a crucial step for progression of heart
      failure (HF). Free radical generation by the failing myocardium has been proposed
      as linked to myocardial remodeling. The aim of this study was to evaluate the
      urinary excretion of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable
      marker for oxidant stress in vivo, and collagen turnover in patients with acute
      worsening of congestive HF. METHODS AND RESULTS: Enrolled were 43 patients with
      acute worsening of congestive HF of various etiologies. On admission (acute
      phase) and after approximately 2 weeks of conventional treatment (chronic phase),
      the following were measured: (1) immunoreactive urinary 8-iso-PGF2alpha, (2)
      serum total antioxidant status (TAS); and (3) serum levels of procollagen type I
      carboxyterminal peptide (PIP) and carboxyterminal collagen type I telopeptide
      (CITP), biochemical markers for collagen synthesis and degradation, respectively.
      From the acute to the chronic phase the parameters changed as follows: 335.1+/
      245.4 to 205.3+/-107.4 pg/mg creatinine for urinary 8-iso-PGF2alpha (p<0.0001);
      0.92+/-0.16 to 0.98+/-0.13 mmol/L for TAS (p<0.01); 171.4+/-72.5 to 93.7+/-33.9
      ng/ml for PIP (p<0.0001); and 7.2+/-3.6 to 12.6+/-8.4 ng/ml for CITP (p<0.0001).
      CONCLUSIONS: Acute worsening of congestive HF promotes free radical generation
      and collagen synthesis.

PMID- 18037743
TI  - Prognostic value of non-obstructive CT low-dense coronary artery plaques detected
      by multislice computed tomography.
AB  - BACKGROUND: The prognostic value of non-obstructive, CT low-dense plaques (CTLDP)
      on multislice computed tomography (MSCT) for the prediction of nonfatal acute
      myocardial infarction (AMI), unstable angina (UA) and cardiac death has not yet
      been defined. METHODS AND RESULTS: In the present study 810 patients who
      underwent MSCT and had non-obstructive coronary artery disease were followed up
      for the occurrence of AMI, UA and cardiac death. Non-obstructive CTLDP were
      defined as plaques with a CT density <68 Hounsfield units, accompanied by mild to
      moderate coronary artery stenosis (25-75%). Patients were followed-up for 1,062+/
      544 days for the occurrence of (1) acute coronary syndrome (ACS) including
      nonfatal AMI and UA, and (2) cardiac death. CTLDP were detected in 189 patients
      (23.3%). The annual event rate of AMI, UA, ACS and cardiac death was 0.91%,
      0.91%, 1.82% and 0.36%, respectively, in patients with CTLDP and 0.10%, 0.55%,
      0.66% and 0.21%, respectively, in patients without CTLDP. The event rate of ACS
      was significantly higher in patients with CTLDP than in those without CTLDP
      (p<0.001). Multivariate Cox proportional regression analysis revealed that
      previous MI and the presence of CTLDP were independent predictors of ACS.
      CONCLUSION: Non-obstructive CTLDP detected by MSCT yield prognostic information
      toward the identification of ACS.

PMID- 18037744
TI  - Clinical validity of longitudinal pre-ejectional myocardial velocity for
      identifying the transmural extent of viable myocardium: early after reperfusion
      of an infarct-related coronary artery.
AB  - BACKGROUND: Positive longitudinal pre-ejectional velocity (+PEVL) was recently
      reported to be a reliable index of myocardial recovery early after successful
      revascularization in myocardial infarction (MI); that is, it recognizes the
      transmural extent of viable myocardium. The applicability of PEVL in the real
      world clinical setting for identifying the transmural extent of viable myocardium
      in reperfused recent MI was assessed. METHODS AND RESULTS: Using tissue Doppler
      imaging, the resting basal and mid myocardial PEVLs were determined within 3 days
      after revascularization in 41 consecutive patients with recent MI. Infarct
      thickness was semi-quantified using delayed gadolinium-enhanced magnetic
      resonance imaging (MRI) at baseline and at 6-month follow up to differentiate
      transmural from nontransmural MI. The proportion of segments showing the presence
      of +PEVL was not significantly changed as infarct thickness increased (p=0.2),
      with 66.2% having +PEVL even in segments involving >75% transmural infarction.
      Moreover, +PEVL was found in a large fraction of segments with akinesia (70.4%).
      Specificity and negative predictive value of +PEVL for assessing infarct
      nontransmurality were disappointingly low (32.0% and 26.9%, respectively). All of
      these results were not altered when the 6-month follow-up MRI was done.
      CONCLUSIONS: +PEVL cannot be regarded as a reliable marker for predicting the
      transmural extent of viable myocardium in recent MI.

PMID- 18037745
TI  - Using transthoracic Doppler echocardiography to diagnose reduced coronary flow
      velocity reserve in the posterior descending coronary artery in children with
      elevated right ventricular pressure.
AB  - BACKGROUND: Advances in transthoracic Doppler echocardiography enable noninvasive
      measurements of coronary flow velocity and coronary flow velocity reserve (CFVR)
      in the posterior descending coronary artery (PD). METHODS AND RESULTS: To
      evaluate CFVR in the PD of children with elevated right ventricular (RV)
      pressure, 19 children with RV pressure overload and 13 age-matched controls with
      normal RV pressure were studied using transthoracic Doppler echocardiography.
      Average peak flow velocity (APV) was measured at rest and in hyperemic conditions
      (intravenous administration of adenosine of 0.16 mg.kg(-1).min(-1)). Compared
      with controls, the PD CFVR was significantly reduced in the patients with
      elevated RV pressure (1.87+/-0.42 vs 2.49+/-0.55, p<0.01) because their mean
      baseline APV was significantly greater (27+/-6 vs 19+/-4 cm/s, p<0.01), although
      hyperemic APV was not significantly different (49+/-10 vs 48+/-14 cm/s, p=NS).
      CONCLUSIONS: PD CFVR is limited in patients with elevated RV pressure because of
      elevation of the baseline resting flow velocity.

PMID- 18037746
TI  - Clinical importance of Koch's triangle size in children: a study using 3
      dimensional electroanatomical mapping.
AB  - BACKGROUND: Catheter ablation inside the Koch's triangle has a risk for complete
      atrioventricular block. METHODS AND RESULTS: The anatomic size of the coronary
      sinus (CS) and His bundle (HB) in children and the distance between them was
      studied using a 3-dimensional electroanatomical mapping system (CARTO). Fifty
      three children (mean age, 11.8+/-3.7 years) without congenital heart disease (ie,
      24 with atrioventricular re-entrant tachycardia, 18 with atrioventricular nodal
      re-entrant tachycardia, 7 with atrial tachycardia, 2 with ventricular tachycardia
      and 2 with atrial flutter) were studied. The size of the HB recording area was
      148+/-97 mm2 and the size of the CS was 66+/-44 mm2. The size of the CS and the
      distance between the HB and CS (18+/-7 mm) were proportional to body weight, body
      length and body surface area. All patients underwent catheter ablation, including
      25 ablations inside Koch's triangle. Catheter ablation was successful in 52
      patients without any atrioventricular nodal injury. CONCLUSIONS: The CS size and
      the distance between the HB and CS increased proportionally with children's
      growth. To know the distance from the HB to the ablation point is useful in
      avoiding atrioventricular node injury, and information about the length of Koch's
      triangle may provide supportive information when applying radiofrequency energy
      inside Koch's triangle without needing to use the CARTO system in children, but
      this merits further investigation.

PMID- 18037747
TI  - Randomized comparison of the continuous vs point-by-point radiofrequency ablation
      of the cavotricuspid isthmus for atrial flutter.
AB  - BACKGROUND: Achievement of complete conduction block in the cavotricuspid isthmus
      (CTI) is a curative ablation technique in patients with common atrial flutter
      (AFL). The present study was a prospective comparison of the efficacy of 2
      ablation strategies in patients with common AFL: the continuous and point-by
      point radiofrequency (RF) delivery techniques. METHODS AND RESULTS: Forty
      patients with common AFL were randomly assigned to either a group treated with a
      continuous RF delivery or to a group undergoing point-by-point RF ablation. In
      the first group, the RF energy was continuously delivered during a slow drag of
      the catheter tip from the tricuspid annulus to the inferior vena cava without
      stopping the application. In the second group, the RF ablation was performed
      using a point-by-point approach for 60 s at each point. All patients underwent
      ablation with an 8-mm-tip ablation catheter with a power limit of 50 W and a
      target temperature of 55 degrees C. Complete CTI conduction block was achieved in
      all patients. The patient characteristics, including the anatomy of the CTI
      estimated by 3-dimensional computed tomography, were no different between the 2
      groups. The procedure time (time from the start of RF delivery to the completion
      of CTI block), fluoroscopic time and total RF energy required to create the CTI
      block between the continuous and point-by-point groups were 7.3+/-5.6 vs 21.2+/
      22.2 min (p<0.01), 7.2+/-4.4 vs 16.2+/-14.1 min (p<0.05), and 15,631+/-6,001 vs
      24,072+/-16,140 joules (p<0.05), respectively. There were no complications or
      recurrences of AFL during the follow-up period in any of the patients.
      CONCLUSION: In the curative treatment of common AFL, the continuous RF delivery
      approach could shorten the procedure and fluoroscopic time and reduce the total
      RF energy compared with the point-by-point RF ablation approach.

PMID- 18037748
TI  - Longitudinal change in renal function in patients with idiopathic dilated
      cardiomyopathy without renal insufficiency at initial diagnosis.
AB  - BACKGROUND: Impaired renal function is associated with poor outcomes among
      patients with chronic heart failure (CHF). However, the long-term changes in
      renal function in CHF patients without renal insufficiency at initial diagnosis
      remain unclear. METHODS AND RESULTS: Retrospective analysis of patients
      presenting with idiopathic dilated cardiomyopathy (IDCM) from 1984 to 2003 and
      who had normal renal function defined as estimated creatinine clearance
      (eCcr)>or=60 ml/min at the first diagnosis. Cumulative event proportions and
      renal insufficiency defined as eCcr<60 ml/min were calculated by the Kaplan-Meier
      method. The predictors of renal insufficiency were evaluated by logistic
      regression analysis. Impaired renal function developed in 20% during an 8-year
      follow-up and in 50% during a 20-year follow-up. Advanced age at the first
      diagnosis, high frequency of admissions, and hypotension during the clinical
      course were associated with the occurrence of impaired renal function. Beta
      blocker therapy was a negative predictor of renal insufficiency. CONCLUSIONS: In
      patients with IDCM without renal insufficiency at initial diagnosis, worsening
      renal function occurred during the follow-up period. Frequent admissions,
      hypotension, and lacking beta-blocker therapy were associated with a poor
      prognosis in renal function.

PMID- 18037749
TI  - A985G polymorphism of the endothelin-2 gene and atrial fibrillation in patients
      with hypertrophic cardiomyopathy.
AB  - BACKGROUND: It was recently suggested that the angiotensin-converting enzyme
      insertion/insertion genotype, which is considered to be protective against
      cardiovascular disease, was a significant risk factor for atrial fibrillation
      (AF) in patients with hypertrophic cardiomyopathy (HCM). The aim of this study
      was to investigate the association between the endothelin-2 (EDN2) A985G
      polymorphism and AF in patients with HCM. METHODS AND RESULTS: The EDN2 A985G
      polymorphism (rs 5800) was genotyped in 110 patients with HCM who had no
      clinically documented AF before medical treatment. The distribution of the EDN2
      genotypes (G/G, G/A, and A/A) was 77.3%, 19.1%, and 3.6%, respectively. The EDN2
      A allele frequency was 0.21 in 26 patients who subsequently developed AF during
      long-term follow-up and 0.11 in 84 patients who remained in sinus rhythm. The
      distribution of genotypes of the dominant EDN2 A allele between the two groups
      was significantly different by chi-square analysis (42.3% vs 16.7%, p=0.014). In
      a multivariate model, the A985 allele of the EDN2 gene was associated with
      increased adjusted risk for the occurrence of AF (p=0.018). CONCLUSION: The EDN2
      A985 allele, which is considered to be protective in cardiovascular disease, may
      be a risk factor for AF in patients with HCM.

PMID- 18037750
TI  - Cardiac sarcoidosis underlies idiopathic dilated cardiomyopathy: importance of
      mediastinal lymphadenopathy in differential diagnosis.
AB  - BACKGROUND: Cardiac sarcoidosis is frequently overlooked or misdiagnosed as
      idiopathic dilated cardiomyopathy (DCM), primarily because of difficulties in its
      diagnosis. This is a crucial issue because appropriate therapy with
      immunosuppressive agents can be initiated if early diagnosis is achieved. METHODS
      AND RESULTS: Thoracic computed tomography (CT) was retrospectively analyzed in
      detail with special reference to lymph node swelling (LNS) in the mediastinum of
      8 patients diagnosed with idiopathic DCM who underwent left ventriculoplasty
      (LVP), and were later proven to have active cardiac sarcoidosis by histological
      evaluation of the resected myocardium. Twenty age-matched patients with
      idiopathic DCM who also underwent LVP served as controls. On conventional chest
      radiographs, none of the cardiac sarcoidosis patients exhibited lymph node
      involvement, including bilateral hilar lymphadenopathy. However, CT demonstrated
      significant mediastinal LNS in 7 (88%) of them and in only 1 (5%) of the 20
      controls. There was a significant difference in the incidence of LNS in the 2
      groups (p=0.00005). CONCLUSION: Evaluation of mediastinal lymphadenopathy by CT
      is an easy and valuable initial screening method for distinguishing cardiac
      sarcoidosis from idiopathic DCM.

PMID- 18037751
TI  - Renal artery stenosis in cardio-and cerebrovascular disease: renal duplex
      ultrasonography as an initial screening examination.
AB  - BACKGROUND: The prevalence and indicative clinical factors of renal artery
      stenosis (RAS) in the Japanese population are unclear. METHODS AND RESULTS: The
      aim of this study was to investigate the prevalence of RAS in a selectively
      referred Japanese population and to determine any clinical factors related to RAS
      by initially screening with renal duplex ultrasonography. The 750 patients
      presenting because of possible or known cardio-and cerebrovascular diseases were
      prospectively studied. Duplex examination was performed in 729 patients (97.2%):
      21 patients (2.8%) did not undergo it, because of technical impossibility. Duplex
      RAS was found in 38 patients (5.2%). Subsequently, a confirmatory renal
      angiography was obtained in 40 patients, investigating those who had duplex RAS
      or no duplex examination. Angiographic RAS was found in 35 patients (4.8%). The
      respective prevalences of duplex and angiographic RAS were 6.3% and 6.7% in
      coronary artery disease, 8.8% and 9.3% in multivessel coronary artery disease,
      7.5% and 8.2% in heart failure, 5.1% and 4.3% in unstable angina pectoris, 20.0%
      and 22.2% in carotid artery stenosis, 10.3% and 10.2% in stroke, 20.0% and 20.0%
      in peripheral artery disease, and 12.0% and 11.8% in abdominal aortic aneurysm.
      Univariate analysis showed that patients with duplex RAS were older and had more
      atherosclerotic risk factors. Furthermore, they were more likely to be smokers
      and have hypertension, renal impairment, renal atrophy, left ventricular
      hypertrophy and cardio- and cerebrovascular diseases. Multivariate stepwise
      analysis showed that smoking, peripheral artery disease, abdominal aortic
      aneurysm and renal atrophy were independent predictors of duplex RAS.
      CONCLUSIONS: RAS is frequent in Japanese patients with cardio- and
      cerebrovascular diseases. Initial screening for RAS by duplex ultrasonography is
      recommended for patients with complications, especially peripheral artery
      disease, abdominal aortic aneurysm and renal atrophy.

PMID- 18037752
TI  - Multidetector-row computed tomography management of acute pulmonary embolism.
AB  - BACKGROUND: The purpose of this study was to evaluate the usefulness and safety
      of multidetector-row computed tomography (MDCT) pulmonary angiography and
      indirect venography management of acute pulmonary embolism (PE), including
      indication for inferior vena cava (IVC) filter. METHODS AND RESULTS: Seventy-one
      consecutive patients who were clinically suspected of PE and underwent 16-slice
      MDCT pulmonary angiography and indirect venography were enrolled. Management
      included indication of IVC filter for patients with extensive deep venous
      thrombosis (DVT) in submassive or massive PE. A right ventricular to left
      ventricular short-axis diameter by MDCT>1.0 was judged as submassive PE. All
      patients were followed for 1 year. MDCT identified 50 patients with venous
      thromboembolism and 47 patients had acute PE: 4 were judged as massive, 14 as
      submassive, and 29 as non-massive by MDCT; 3 patients had DVT alone and 7
      patients had caval or iliac DVT. Only 1 patient with massive PE and DVT near the
      right atrium died of recurrence. No other patients died of PE. CONCLUSION:
      Management based on MDCT pulmonary angiography combined with indirect venography
      is considered to be safe and reliable in patients with suspected acute PE.

PMID- 18037753
TI  - Relationship between insulin-like growth factor-I and brain natriuretic peptide
      in patients with acromegaly after surgery.
AB  - BACKGROUND: Increased cardiac insulin-like growth factor (IGF)-I production is
      associated with physiological cardiac hypertrophy in athletes, and IGF-I has been
      recognized as a cardioprotective agent in experimental animal studies. On the
      other hand, acromegaly which is characterized by an excess of IGF-I has been
      linked to impaired cardiac function. METHODS AND RESULTS: Both the relationship
      between the serum levels of IGF-I and brain natriuretic peptide (BNP), which is
      released from the cardiac ventricles in response to ventricular stress, and that
      between IGF-I and the concentrations of the plasma amino-terminal propeptide of
      procollagen type III (P-III-P), which is associated with myocardial fibrosis,
      were evaluated in 19 patients after surgical treatment for acromegaly.
      Echocardiography revealed that left ventricular systolic function and dimensions
      were within normal range in all patients. Significant inverse correlations were
      found between IGF-I and the BNP (r=-0.5, p=0.02) and P-III-P levels (r=-0.62,
      p=0.005). CONCLUSION: We observed an inverse significant relationship between IGF
      I and both the BNP and P-III-P value in surgically treated acromegaly patients.
      These observations suggest that appropriate levels of IGF-I have beneficial
      cardioprotective effects after surgery in patients with acromegaly.

PMID- 18037754
TI  - Angiotensin II type 1a receptor signals are involved in the progression of heart
      failure in MLP-deficient mice.
AB  - BACKGROUND: Angiotensin II (AT) is implicated in the development of cardiac
      remodeling, which leads to heart failure, and pharmacological inhibition of the
      AT type 1 (AT1) receptor has improved mortality and morbidity in patients of
      heart failure. The aim of this study was to elucidate the role of the AT1
      receptor in disease progression in muscle LIM protein (MLP)-deficient mice, which
      are susceptible to heart failure because of defective function of mechanosensors
      in cardiomyocytes. METHOD AND RESULTS: Hearts from MLP knockout (MLPKO) mice and
      MLP-AT1a receptor double knockout (DKO) mice were analyzed. MLPKO hearts showed
      marked chamber dilatation with cardiac fibrosis and reactivation of the fetal
      gene program. All of these changes were significantly milder in the DKO hearts.
      Impaired left ventricular (LV) contractility and filling were alleviated in DKO
      hearts. However, the impaired relaxation and downregulated expression of
      sarcoplasmic reticulum calcium-ATPase 2 were unchanged in DKO hearts.
      CONCLUSIONS: The AT1a receptor is involved in progression of LV remodeling and
      deterioration of cardiac function in the hearts of MLPKO mice. These results
      suggest that blockade of the receptor is effective in preventing progression of
      heart failure in dilated cardiomyopathy.

PMID- 18037755
TI  - Sildenafil citrate (Viagra) enhances vasodilatation by atrial natriuretic peptide
      in normal dogs.
AB  - BACKGROUND: Sildenafil citrate (Viagra) is a selective inhibitor of cyclic
      guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might
      enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide
      (ANP) in patients with heart failure. The objective of this study was to examine
      the combined effect of Viagra on hemodynamic changes during infusion of exogenous
      ANP. METHODS AND RESULTS: Healthy male beagles were used to assess systemic blood
      pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After
      hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given
      during this study. One hour after initiating infusion of ANP, 2 mg/kg of
      sildenafil citrate or vehicle was given orally via a nasogastric tube.
      Hemodynamic changes were measured before and 1 h after these administrations.
      Mean systemic and PAP decreased during infusion of ANP, and further decreased
      after sildenafil citrate administration, however, mean systemic blood pressure
      decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil
      citrate administration. CONCLUSION: In normal dogs, sildenafil citrate enhances
      the vasodilator effect of ANP by increasing the cGMP level, however, the
      concomitant use of sildenafil citrate with ANP will not induce severe
      hypotension.

PMID- 18037756
TI  - Beneficial effects of the dual L- and T-type Ca2+ channel blocker efonidipine on
      cardiomyopathic hamsters.
AB  - BACKGROUND: The T-type Ca2+ channel (TCC) is activated, and abnormalities of the
      TCC may be related to the pathogenesis of Ca2+ overload, in cardiomyopathic
      hamster hearts. The aims of the present study were to investigate the alteration
      in expression of the TCC and to examine the effects of a dual L-and T-type Ca2+
      channel blocker, efonidipine (EFO), on cardiac function and TCC during
      development of heart failure in UM-X7.1 cardiomyopathic hamsters. METHODS AND
      RESULTS: UM-X7.1 and golden hamsters were examined, and EFO was administered at
      the age of 20 weeks for 4 weeks. Cardiac function was examined, the expression of
      TCCalpha1G was measured, and ventricular myocytes were subjected to a patch-clamp
      study. At 24 weeks, vehicle-treated UM-X7.1 hamsters exhibited significant
      increases in left ventricular (LV) size, with marked decreases in ejection
      fraction (LVEF) compared with golden hamsters. In the UM-X7.1 group, the
      expression of TCCalpha1G increased during development of heart failure compared
      with the golden hamster group. In the UM-X7.1 group, EFO treatment significantly
      attenuated the decrease of LVEF without affecting blood pressure compared with
      the vehicle group. EFO treatment decreased heart rate (by approximately 10%) in
      both groups. In the golden hamster group, EFO treatment did not affect LV
      function. The TCC current in ventricular myocytes was significantly increased in
      UM-X7.1, and was inhibited by EFO in a dose-dependent manner. CONCLUSIONS: In
      cardiomyopathic hamster hearts, abnormalities in the TCC may be at least in part
      related to the pathogenesis of abnormal Ca2+ homeostasis, and TCC-blocker
      treatment may decrease the TCC current, resulting in an improvement of cardiac
      function. TCC blocker therapy might be a new strategy for certain types of heart
      failure.

PMID- 18037757
TI  - Reverse-remodeling effects of angiotensin II type 1 receptor blocker in a canine
      atrial fibrillation model.
AB  - BACKGROUND: The reverse-remodeling effect of angiotensin II type 1 receptor
      blocker (ARB) on atrial fibrillation (AF) is unclear. METHODS AND RESULTS:
      Sustained AF was induced in 20 dogs by 4-week rapid atrial pacing. The AF
      duration, atrial effective refractory period (AERP) and intra-atrial conduction
      time (CT) were measured every 2 weeks. After 4-week pacing, dogs were randomly
      assigned to control (n=10) and ARB (olmesartan; n=10) groups. Olmesartan was
      administered orally (3 mg.kg(-1).day(-1)) after pacing was terminated, and
      continued for the 4-week recovery period. After 4-week pacing, AERP shortening,
      CT prolongation and AF maintenance were not significantly different between the 2
      groups. During the recovery, AERP recovered to baseline in both groups. CT
      remained prolonged in the control group during the recovery, but recovered to
      baseline in the olmesartan group. The mean AF duration in the olmesartan group
      after 4-week-recovery was significantly shorter than that in the control group
      (58+/-20 vs 1,337+/-226 s, p<0.001). Olmesartan significantly decreased
      interstitial fibrosis compared with the control group (9+/-1% vs 15+/-1 at the
      right atrial appendage, p<0.001). CONCLUSION: Olmesartan has a reverse-remodeling
      effect on AF-induced structural changes, indicating that it may be useful for
      preventing AF recurrence after the termination of sustained AF.

PMID- 18037758
TI  - Successful catheter ablation of left ventricular epicardial tachycardia
      originating from the great cardiac vein: a case report and review of the
      literature.
AB  - A patient underwent radiofrequency (RF) catheter ablation for a drug-refractory
      ventricular tachycardia, but RF energy application at an endocardial site of the
      left ventricular outflow tract and at the left sinus of Valsalva could not
      eliminate the tachycardia. The earliest ventricular activation during the
      arrhythmia, which preceded the onset of the QRS complex by 32 ms, was found
      within the great cardiac vein and complete elimination of the tachycardia was
      finally achieved with RF application at that site.

PMID- 18037759
TI  - Pulmonary vein isolation in patients with paroxysmal atrial fibrillation after
      direct suture closure of congenital atrial septal defect.
AB  - Two cases of paroxysmal atrial fibrillation (AF) first occurred 15 and 36 years,
      respectively, after isolated direct suture closure of an atrial septal defect
      (ASD) and failed to be controlled by antiarrhythmic drug therapy. In these cases,
      an atrial transseptal procedure was feasible and no residual iatrogenic ASD was
      observed, even after multiple procedures. Pulmonary vein (PV) isolation was also
      feasible and safe and could eliminate the AF completely. PV isolation may become
      an alternative to antiarrhythmic drug therapy in patients with paroxysmal AF
      occurring late after an isolated direct suture closure of an ASD.

PMID- 18037760
TI  - Catecholamine cardiomyopathy associated with paraganglioma rescued by
      percutaneous cardiopulmonary support: inverted Takotsubo contractile pattern.
AB  - A case of catecholamine cardiomyopathy associated with paraganglioma, which was
      rescued by percutaneous cardiopulmonary support system (PCPS), is presented.
      Unlike typical apical ballooning, transthoracic echocardiography and left
      ventriculography revealed severe left ventricular (LV) dysfunction and an
      abnormal contractile pattern, consisting of akinesis of the basal and
      midventricular segments and hyperkinesis of the apical segments. Because of the
      intractable cardiogenic shock, despite conventional treatment, PCPS was
      performed. The underlying disease was paraganglioma. Catecholamine excess may
      induce not only transient LV apical ballooning but also atypical LV ballooning
      without involvement of the LV apex. Early use of PCPS is important for the
      patient with a catecholamine crisis who is not stabilized by intra-aortic balloon
      pump as well as infusion of fluid and inotropic agents.

PMID- 18037761
TI  - Rupture of aneurysmal circumflex coronary artery into the left atrium after
      ligation of its arteriovenous fistula.
AB  - Aneurysmal circumflex coronary artery (Cx) with fistulous connection to the
      coronary sinus is a rare clinical entity that usually remains asymptomatic until
      later in life, so the ideal therapeutic strategy is poorly defined. The timing of
      surgical treatment for asymptomatic patients is a big issue, and whether to leave
      or exclude the diffuse aneurysm in addition to ligation of the fistula is
      controversial, considering the native myocardial circulation. Complete surgical
      repair, including exclusion of a diffusely aneurysmal Cx and coronary
      revascularization to a graftable branch in the circumflex area combined with
      ligation of its fistula, is quite challenging and sometimes fatal because of a
      broad posterolateral myocardial infarction without revascularization caused by a
      lack of graftable branches. A case of diffuse aneurysmal Cx, which ruptured into
      the left atrium after surgical ligation of its fistulous connection to the
      coronary sinus, is presented. Simple ligation of the fistula, leaving a gigantic
      aneurysmal circumflex artery, is hazardous for later rupture and should be
      avoided. Therapeutic strategies for this complex disorder are discussed,
      including the optimal timing of surgical treatment.

PMID- 18037762
TI  - The risk factors for thromboembolism in nonvalvular atrial fibrillation and
      CHADS2 scoring in Japan.

PMID- 18037764
TI  - Misuse of regression analysis and correlation in "new criteria for 'obesity
      disease' in Japan".

PMID- 18037765
TI  - Synchronicity and ventricular arrhythmias in hypertension.

PMID- 18037766
TI  - Adenosine and cardioprotection in chronic heart failure: genes and protein
      expression.

PMID- 18037767
TI  - Impaired left ventricular systolic synchronicity in hypertensive patients with
      ventricular arrhythmias.
AB  - Left ventricular (LV) systolic synchronicity is impaired in hypertensive
      patients. Ventricular arrhythmias often co-exist in hypertensive patients;
      hypertension and ventricular arrhythmias have an adverse impact on cardiac
      function. However, the influence of ventricular arrhythmias on LV synchronicity
      was not clear. The objective of the present study was to investigate the
      influence of ventricular arrhythmias on LV synchronicity in hypertensive
      patients. Tissue Doppler imaging (TDI) was performed in 136 subjects. Group 1
      consisted of 74 hypertensives without any arrhythmias; group 2 consisted of 30
      hypertensive patients with ventricular arrhythmias; and the control group
      consisted of 32 normal subjects. Using three apical views, LV synchronicity was
      assessed by the maximal differences in time to peak myocardial systolic
      contraction (T(s)) and early diastolic relaxation (T(e)) between any two of the
      LV segments (T(s)-max, T(e)-max) and the standard deviation of T(s) (T(s)-SD) and
      T(e) (T(e)-SD) of all 12 segments. T(s)-max was significantly prolonged in group
      2 compared with group 1 and the control group (93.70 +/- 20.97 ms vs. 79.48 +/-
      25.46 ms [p<0.01] or 53.83 +/- 15.42 ms [p<0.001], respectively). T(s)-SD was
      also significantly prolonged in group 2 compared with group 1 and the control
      group (38.16 +/- 5.82 ms vs. 33.37 +/- 6.04 ms [p<0.05] or 24.01 +/- 3.58 ms
      [p<0.001], respectively). In conclusion, LV systolic synchronicity was impaired
      in hypertensive patients with ventricular arrhythmias, and TDI was shown to be
      useful for the detection of myocardial abnormalities in such patients.

PMID- 18037768
TI  - Associations of brachial-ankle pulse wave velocity and carotid atherosclerotic
      lesions with silent cerebral lesions.
AB  - Silent cerebral lesions are increasingly found in mass screenings using MRI and
      magnetic resonance angiography (MRA). The purpose of this paper is to assess the
      usefulness of two non-invasive clinical tests-carotid ultrasound examination and
      brachial-ankle pulse wave velocity (baPWV) measurement-for predicting silent
      cerebral infarction (SCI) and silent intracranial arterial stenosis. Data were
      collected on 480 asymptomatic adult subjects who participated in a brain
      screening program at a single hospital between April 2003 and March 2006. All
      participants underwent baPWV measurement, B-mode ultrasonography of carotid
      arteries, MRI, and MRA. Data on 476 (99.1%) subjects were included in the
      analysis. Among these, 273 (57.4%) were male and the mean age was 51.5 years; 161
      (33.8%) had carotid plaque; 33 (6.9%) had increased intima-media thickness (IMT);
      99 (20.8%) had SCI; and 7 (1.5%) had intracranial arterial stenosis. The
      multivariate analysis showed that age (odds ratio [OR]: 1.12; 95% confidence
      interval [CI]: 1.08-1.17), carotid plaque (OR: 2.69; 1.59-4.56), increased IMT
      (OR: 2.40; 1.02-5.65), and a history of hypertension treatment (OR 2.22; 1.11
      4.43) were significantly associated with SCI. Also, increased IMT (OR 9.70: 1.48
      63.71) was related to intracranial arterial stenosis. Brachial-ankle PWV was
      related to SCI (p<0.01) and intracranial stenosis (p=0.01) in univariate analysis
      but not in multivariate analysis. The presence of carotid plaque and that of
      increased IMT on ultrasound examination are useful for assessing the risk of SIC.
      Increased IMT is also predictive of intracranial arterial stenosis.

PMID- 18037769
TI  - Pycnogenol, French maritime pine bark extract, augments endothelium-dependent
      vasodilation in humans.
AB  - Pycnogenol, an extract of bark from the French maritime pine, Pinus pinaster
      Ait., consists of a concentrate of water-soluble polyphenols. Pycnogenol contains
      the bioflavonoids catechin and taxifolin as well as phenolcarbonic acids.
      Antioxidants, such as bioflavonoids, enhance endothelial nitric oxide (NO)
      synthase expression and subsequent NO release from endothelial cells. The purpose
      of this study was to determine Pycnogenol's effects on endothelium-dependent
      vasodilation in humans. This was a double-blind, randomized, placebo and active
      drug study. We evaluated forearm blood flow (FBF) responses to acetylcholine
      (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP),
      an endothelium-independent vasodilator, in healthy young men before and after 2
      weeks of daily oral administration of Pycnogenol (180 mg/day) (n=8) or placebo
      (n=8). FBF was measured by using strain-gauge plethysmography. Neither the
      placebo nor Pycnogenol altered forearm or systemic hemodynamics. Pycnogenol, but
      not placebo, augmented FBF response to ACh, from 13.1 +/- 7.0 to 18.5 +/- 4.0
      mL/min per 100 mL tissue (p<0.05). SNP-stimulated vasodilation was similar before
      and after 2 weeks of treatment in the control and Pycnogenol groups. The
      administration of N(G)-monomethyl-L-arginine, an NO synthase inhibitor,
      completely abolished Pycnogenol-induced augmentation of the FBF response to ACh.
      These findings suggest that Pycnogenol augments endothelium-dependent
      vasodilation by increasing in NO production. Pycnogenol would be useful for
      treating various diseases whose pathogeneses involve endothelial dysfunction.

PMID- 18037770
TI  - Impact of adenosine receptor signaling and metabolism on pathophysiology in
      patients with chronic heart failure.
AB  - Adenosine is well known to be a cardioprotective substance in ischemic heart
      disease. However, the modulation of adenosine receptors and the production and
      degradation of endogenous adenosine in chronic heart failure (CHF) are not fully
      understood. We analyzed the gene expression patterns of adenosine-related genes
      in human failing and nonfailing myocardium using DNA microarray analysis and
      quantitative real time-polymerase chain reaction (RT-PCR). DNA microarray
      analysis revealed that the gene expression of adenosine A2a, A2b, and A3
      receptors (A2aR, A2bR, and A3R) as well as that of adenosine deaminase (ADA)
      decreased in failing myocardium. The down-regulation of these genes was verified
      by quantitative RT-PCR. We also measured the activities of these adenosine
      metabolism-related enzymes in failing myocardium and cardiac adenosine levels in
      patients with CHF. In CHF patients, we observed the decreased enzyme activity of
      ADA and the elevation of cardiac adenosine levels in CHF patients. To enhance the
      signaling of adenosine receptors, we increased plasma adenosine levels using
      dipyridamole, which decreased the severity of CHF. The gene expression of A2aR,
      A2bR, A3R, and ADA was decreased in the failing hearts, and this decrease may
      impair adenosine-related signal transduction. The activities of adenosine-related
      enzymes were altered, thus increasing the myocardial adenosine levels; this
      increase may compensate for the impairment of adenosine-related signal
      transduction in patients with CHF. The impairment of adenosine-related signal
      transmission contributes to the pathophysiology of CHF.

PMID- 18037771
TI  - Haplotype-based case-control study of the association between the guanylate
      cyclase activator 2B (GUCA2B, Uroguanylin) gene and essential hypertension.
AB  - Uroguanylin (gene name: guanylate cyclase activator 2B, GUCA2B) is a peptide
      regulator of intestinal salt and water transport. It has been reported that the
      uroguanylin knockout mouse exhibits elevated blood pressure. Therefore, the
      GUCA2B gene is thought to be a susceptibility gene for essential hypertension
      (EH). Despite extensive studies, however, the relationship between the GUCA2B
      gene and EH has not yet been defined. The aim of this study was to assess the
      association between the human GUCA2B gene and EH. Using four single nucleotide
      polymorphisms (SNPs), we conducted a genetic association study in 281 EH patients
      and 279 age-matched normotensive (NT1) individuals. To derive more reliable data,
      we performed a duplicate case-control study in which we recruited another
      normotensive group (NT2). There was no significant difference in the overall
      distribution of alleles for any of the SNPs between the EH and NT1 groups, or
      between the EH and NT2 groups. Therefore, these four SNPs cannot be the genetic
      markers for EH. The occurrences of the C-A haplotype (rs883062-rs1047047) and the
      C-A-G haplotype (rs883062-rs1047047-rs2297566) were significantly higher in the
      EH group than in the NT1 group (p<0.0001) or the NT2 group (p<0.0001). These
      results suggest that the C-A haplotype and the C-A-G haplotype of the GUCA2B gene
      are the genetic markers for EH, and that GUCA2B or a neighboring gene might be a
      susceptibility gene for EH.

PMID- 18037772
TI  - Renal-protective effect of T-and L-type calcium channel blockers in hypertensive
      patients: an Amlodipine-to-Benidipine Changeover (ABC) study.
AB  - Both strict blood pressure control and efferent artery dilatation are critical in
      reducing proteinuria, which in turn helps to regulate blood pressure. Benidipine,
      an L- and T-type calcium channel blocker, has the potential for increased
      effectiveness compared with L-type-dominant calcium channel blockers such as
      amlodipine. Therefore, we evaluated blood pressure and proteinuria after
      changeover from amlodipine to benidipine in poorly controlled hypertensive
      patients. Fifty-eight hypertensive outpatients undergoing amlodipine treatment
      and unable to achieve optimal blood pressure as determined by Japanese Society of
      Hypertension Guidelines for the Management of Hypertention (JSH 2004) were
      changed over to benidipine treatment. We measured blood pressure and pulse rate
      and assessed urinary protein excretion before and after changeover. Systolic and
      diastolic blood pressure dropped from 151/90 mmHg to 140/81 mmHg (p<0.0001). Mean
      blood pressure (p<0.0001) and pulse pressure (p=0.0069) were also reduced, but
      pulse rate increased from 75 bpm to 78 bpm (p=0.0047). Urinary protein excretion
      adjusted for urinary creatinine was reduced from 0.35 +/- 0.82 to 0.22 +/- 0.55
      g/g creatinine (p=0.0119). The urinary protein reduction was observed only in
      patients with renin-angiotensin inhibition (p=0.0216). By switching from
      amlodipine to benidipine treatment, more than 80% of patients reduced their blood
      pressure, and more than 40% achieved optimal blood pressure. Higher urinary
      protein excretion (p<0.0001), lower glomerular filtration rate (p=0.0011) and
      presence of diabetes (p=0.0284) were correlated with reduction of urinary
      proteins during changeover. Taken together, our results suggest that benidipine
      may have greater efficacy than amlodipine in reducing blood pressure and
      proteinuria.

PMID- 18037773
TI  - Design and baseline characteristics of an observational study in Japanese
      patients with hypertension: Japan Hypertension Evaluation with Angiotensin II
      Antagonist Losartan Therapy (J-HEALTH).
AB  - The Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy
      (J-HEALTH) study is a nationwide, prospective, multicenter observational study
      that was designed to enroll hypertensive Japanese patients (>30,000 subjects).
      The patients in this study received treatment with open-label losartan, an
      angiotensin II receptor antagonist, for a maximum of 5 years. This report
      summarizes the study protocol and the baseline characteristics of the patients.
      Between June 2000 and May 2002, patients were screened in all 47 prefectures
      around Japan. Among the 31,515 patients screened, 31,048 patients were enrolled
      in this study and treated with losartan at a daily dose of 25-50 mg. These
      patients were 62.4 +/- 12.1 years old (mean +/- SD) and the mean clinic
      systolic/diastolic blood pressure (BP) values were 165.3 +/- 17.3/94.3 +/- 11.7
      mmHg (mean +/- SD). The complications of hyperlipidemia, diabetes mellitus,
      cardiovascular disease, and cerebrovascular disease were also present in 38.5%,
      13.1%, 8.0%, and 4.4% of patients, respectively. Regarding the World Health
      Organization classification, grade 2 hypertension was most frequent in this
      patient cohort. Nearly 10,000 patients agreed to perform home BP monitoring and
      report details regarding their lifestyles at baseline. Among the patients, 4.2%
      had white coat hypertension at the baseline. The J-HEALTH study is expected to
      provide valuable information about the significance of clinic and home BP control
      and home BP monitoring for the management of hypertension in Japanese patients.

PMID- 18037774
TI  - The effect of combination therapy with an L/N-Type Ca(2+) channel blocker,
      cilnidipine, and an angiotensin II receptor blocker on the blood pressure and
      heart rate in Japanese hypertensive patients: an observational study conducted in
      Japan.
AB  - Recently, the use of combination therapy with a calcium channel blocker (CCB) and
      an angiotensin II receptor blocker (ARB) has been rapidly increasing. Although
      this combination therapy is accepted as a standard treatment hypertension, there
      have been few large-scale, multicenter studies examining its safety and efficacy.
      The present study was designed to investigate the safety and efficacy of adding
      cilnidipine, a dual L/N-type CCB, to the regimen of patients whose blood pressure
      had been poorly controlled (systolic blood pressure [SBP] >140 mmHg or diastolic
      blood pressure [DBP] >90 mmHg) by antihypertensive monotherapy with an ARB. The
      percentage achievement of the blood pressure goals recommended by the JSH 2000
      guidelines was also assessed for at least 12 weeks of treatment. A total of 2,920
      patients were enrolled in the study at 471 institutions in Japan from February
      2003 to July 2004. The incidence of adverse reactions related to cilnidipine was
      as low as 2.5%. A significant reduction from the baseline was found both in SBP
      (from 164.1 +/- 15.3 to 139.2 +/- 15.3 mmHg, p<0.0001) and DBP (from 91.7 +/-
      11.4 to 79.3 +/- 10.7 mmHg, p<0.0001). A total of 31.5% of the patients achieved
      the blood pressure goals recommended by the JSH 2000 guidelines. Moreover, the
      heart rate also significantly decreased in these patients, particularly in those
      with a higher baseline heart rate. Our results indicate that cilnidipine can be
      used in combination with an ARB to control blood pressure without any significant
      adverse effects, and also that cilnidipine successfully reduces elevated heart
      rate, which is a possible risk factor for cardiovascular events.

PMID- 18037775
TI  - Fatty liver and uric acid levels predict incident coronary heart disease but not
      stroke among atomic bomb survivors in Nagasaki.
AB  - Relationships between fatty liver and coronary heart disease (CHD) and stroke
      risk remain ill defined. We investigated whether fatty liver is a predictor of
      CHD and stroke risk. Until December 2000 we followed 2,024 atomic bomb survivors
      (775 men: 62.0 +/- 9.9 years old; 1,249 women: 63.2 +/- 8.4 years old) who had
      basic examinations between November 1990 and October 1992 for clinical and
      laboratory CHD risk factors and fatty liver and who were initially free of CHD
      and stroke. Forty-nine cases of CHD and 84 cases of stroke were observed. At the
      time of the baseline examinations, significant clinical associations were found
      between fatty liver and obesity (p<0.001), hypertension (p<0.001), dyslipidemia
      (p<0.001), and glucose intolerance (p<0.001). A slight but nonsignificant
      association was found between fatty liver and hyperuricemia (p=0.07) as well. By
      using multiple Cox regression analyses, age (relative risk [RR] 1.05, 95%
      confidence interval [CI] 1.01-1.08), smoking (RR 2.20, 95% CI 1.02-4.74),
      hyperuricemia (RR 2.30, 95% CI 1.08-4.89), and fatty liver (RR 2.53, 95% CI 1.06
      6.06) were shown to be significant predictors of CHD, whereas age (RR 1.08, 95%
      CI 1.06-1.10), smoking (RR 2.06, 95% CI 1.14-3.72), and hypertension (RR 2.14,
      95% CI 1.38-3.30) predicted stroke risk. Fatty liver, which clusters clinical and
      laboratory CHD risk factors, is an independent predictor of CHD, but not of
      stroke. Fatty liver should be followed as a feature of metabolic syndrome, with
      the aim of preventing CHD.

PMID- 18037776
TI  - Effectiveness of add-on low-dose diuretics in combination therapy for
      hypertension: losartan/hydrochlorothiazide vs. candesartan/amlodipine.
AB  - In guidelines, a combination therapy of two or more antihypertensives is
      recommended for treatment of hypertension where monotherapy is ineffective.
      Although diuretics or calcium channel blockers are commonly used as add-ons to
      angiotensin receptor blocker (ARB), the most effective and safe combination has
      not been established. In this randomized 4-month study, the efficacy and safety
      were compared between an ARB/diuretics (losartan/hydrochlorothiazide [HCTZ])
      combination and the most prescribed combination, ARB/calcium channel blocker
      (candesartan/amlodipine) in hypertensive patients for whom 8 mg/day of
      candesartan proved ineffective. After 36 patients were recruited and allocated
      into two groups, changes in blood pressure (BP) and laboratory values were
      analyzed in 31 patients: 16 patients received losartan (50 mg/day)/HCTZ (12.5
      mg/day) (L/H group), and 15 patients received candesartan (8 mg/day)/amlodipine
      (5 mg/day) (C/A group) after 5 patients were withdrawn. After 4 months, L/H
      significantly (p<0.001) reduced mean systolic BP (SBP)/diastolic BP (DBP) from
      baseline 160/89 +/- 13/11 mmHg to 140/80 +/- 9/8 mmHg, and C/A reduced BP from
      161/90 +/- 10/11 mmHg to 141/79 +/- 10/7 mmHg. The efficacy in reducing BP was
      similar between the two combination therapies. L/H significantly reduced serum
      potassium, but within the normal range, and did not increase serum uric acid or
      serum triglyceride. With L/H, the percentage of patients who attained the BP goal
      in SBP was higher in elderly patients than in younger patients. As L/H is more
      cost-effective than candesartan/amlodipine and has fewer adverse effects on uric
      acid and other metabolic parameters than diuretic monotherapy, it is concluded to
      be useful for the management of hypertension.

PMID- 18037777
TI  - The incidence and risk factors of renal artery stenosis in patients with severe
      carotid artery stenosis.
AB  - We previously showed that renal artery stenosis (RAS) was commonly found in
      patients with cardiovascular disease (CVD) such as myocardial infarction, stroke,
      or abdominal aneurysm. The aim of the present study was to evaluate the incidence
      and risk factors for RAS in patients with severe carotid artery stenosis (CAS)
      considered to need carotid endarterectomy. From February to August 2006, 41
      consecutive patients with severe CAS were admitted to the Department of
      Neurosurgery of the National Cardiovascular Center. Each patient was examined for
      renal function and urinary albumin excretion, and renal artery duplex scanning
      was also performed. The patients were classified into two groups according to the
      findings of renal Doppler sonography, 11 patients with RAS and 30 patients
      without RAS. We evaluated the differences in clinical findings and renal function
      between the groups and clarified the risk factors for RAS. In RAS patients,
      smoking and incidence of other CVDs were evident, and renal function was impaired
      significantly compared with the patients without RAS. Multivariate logistic
      regression showed that the presence of other CVDs, renal function, and smoking
      were significant clinical predictors for RAS. In patients with severe CAS, RAS
      was frequently detected with the same frequency as ischemic heart disease. The
      RAS risk factors were the presence of other CVDs, renal dysfunction, and smoking.
      Since RAS is an underlying cause of hypertension and renal failure, it is
      important to consider the presence of RAS in patients with severe CAS.

PMID- 18037778
TI  - Reproducibility of masked hypertension determined from morning and evening home
      blood pressure measurements over a 6-month period.
AB  - Recently, the existence of so-called masked hypertension has attracted attention.
      In this study, the reproducibility of masked hypertension determined from morning
      and evening home blood pressure measurements was examined over a 6-month period.
      Home blood pressure measurements were taken consecutively for 7 days in
      volunteers at a company in 2002 and again in 2003. The 503 Japanese subjects (329
      male, 174 female, mean age: 39.4 years), who were not taking antihypertensive
      drugs, were asked to measure their home blood pressure three times every morning
      and three times every evening. We defined casual blood pressure > or =140
      (systolic) or > or =90 (diastolic) mmHg and home blood pressure > or =135 or > or
      =85 mmHg as hypertension. We also defined normotension as <140 and <90 mmHg in
      casual blood pressure and <135 and <85 mmHg in home blood pressure. We examined
      the reproducibility of four blood pressure categories (normotension,
      hypertension, white-coat hypertension, and masked hypertension) over a 6-month
      period. When measured in morning home blood pressure, the reproducibility of
      masked hypertension (59.1%) was significantly higher than that of white-coat
      hypertension (25.0%) and similar to that of hypertension (67.6%). However, the
      reproducibility of masked hypertension (23.5%) was similar to that of white-coat
      hypertension (32.0%) and significantly lower than that of hypertension (66.7%)
      when determined using evening home blood pressure. The concordances in the four
      blood pressure categories between the two periods were 0.582 (kappa coefficient)
      and 0.463 when determined using morning and evening home blood pressure data,
      respectively. In conclusion, the reproducibility of masked hypertension over a 6
      month period was moderate in an urban Japanese population when evaluated by
      morning home blood pressure.

PMID- 18037779
TI  - Prehypertensive renin-angiotensin-aldosterone system blockade in spontaneously
      hypertensive rats ameliorates the loss of long-term vascular function.
AB  - Arterial function after long-term hypertension is characterized by remodeling,
      endothelial dysfunction and reduction of previously enhanced contractile
      responses. We investigated whether transient prehypertensive renin-angiotensin
      aldosterone system (RAAS) blockade modifies long-term arterial function. Wistar
      Kyoto rats (WKY) (i) and spontaneously hypertensive rats (SHR) (ii) were
      prehypertensively (week 4-8) treated with losartan (iii) or spironolactone (iv)
      (20 and 0.5 mg/kg/day, respectively) and investigated at 8 and 72 weeks of age.
      Systolic blood pressure (SBP) was measured intra-arterially. In isolated
      mesenteric arteries, active wall stress (AWS), relaxation in response to
      acetylcholine and wall-to-lumen ratio (W/L) were assessed. Western blotting and
      immunofluorescent staining of whole-mount arterial preparations and two photon
      laser scanning microscopy (TPLSM) were performed to quantify endothelial nitric
      oxide synthase (eNOS) and analyze its intracellular distribution. In 8-week-old
      SHR treatments were found to have reduced SBP. Relaxation, contractile responses
      and vascular morphology remained unaffected irrespective of treatment. At 72
      weeks, SBP was similar in all SHR groups ((i) 129+/-6, (ii) 222 +/- 10, (iii) 210
      +/- 16, (iv) 214 +/- 9 mmHg). Relaxation and maximum AWS were enhanced after
      treatments. W/L demonstrated hypertrophy ((i) 0.10 +/- 0.01, (ii) 0.16 +/- 0.02,
      (iii) 0.15 +/- 0.01, (iv) 0.17 +/- 0.01). Untreated SHR (p<0.01), SHR treated
      with losartan and SHR treated with spironolactone (p<0.05) showed less eNOS as
      compared to WKY. In treated SHR eNOS was concentrated in a perinuclear
      endothelial cell compartment. In conclusion, these findings demonstrate that
      transient prehypertensive blockade results in a long-lasting and blood pressure
      independent improvement of arterial contractility and endothelium-dependent
      vasodilatation that persists in aging SHR. This might be associated with an
      intracellular redistribution of eNOS in the endothelial cell layer.

PMID- 18037780
TI  - Beneficial effects of pioglitazone on left ventricular hypertrophy in genetically
      hypertensive rats.
AB  - Beneficial effects of thiazolidinediones, peroxisome proliferator-activated
      receptor gamma (PPARgamma) agonists, on cardiovascular injuries have been
      reported. However, the effects of these agonists on left ventricular (LV)
      hypertrophy have not been clarified. To investigate whether pioglitazone improves
      LV hypertrophy, we used 32-week-old stroke-prone spontaneously hypertensive rats
      (SHR-SP) that had been treated or not treated with pioglitazone (10 mg/kg/day)
      for 8 weeks, and Wistar Kyoto rats (WKY). We evaluated LV geometry by
      echocardiography; myocyte hypertrophy, tissue fibrosis, and appearance of
      myofibroblasts by histological examination; mRNA expression by real-time
      polymerase chain reaction (PCR); protein expression by Western blot; activities
      of matrix metalloproteinase (MMP) by zymography; and production of reactive
      oxygen species (ROS) by electron spin resonance spectroscopy or thiobarbituric
      acid reactive substances (TBARS). SHR-SP showed concentric hypertrophy of the LV,
      but WKY did not. The myocyte diameter, fraction of tissue fibrosis, and number of
      myofibroblasts were greater in SHR-SP. mRNA expressions of collagen type I and
      type III, tissue growth factor (TGF)-beta1, and brain natriuretic peptide (BNP);
      protein expression of connective tissue growth factor (CTGF); activities of MMP2
      and MMP9; and ROS were increased in SHR-SP. Pioglitazone did not decrease blood
      pressure, but partially normalized LV geometry in addition to decreasing myocyte
      diameter, interstitial fibrosis and number of myofibroblasts; mRNA levels of
      collagen type I and BNP; MMP2 activity; and protein level of CTGF. However, the
      mRNA level of collagen type III and TGF-beta1, MMP9 activity, and ROS production
      were not improved. In conclusion, pioglitazone reversed the concentric LV
      remodeling independently from blood pressure or oxidative stress in chronic
      hypertension.

PMID- 18037781
TI  - Peptide mimotopes of complex carbohydrates in Salmonella enterica serovar typhi
      which react with both carbohydrate-specific monoclonal antibody and polyclonal
      sera from typhoid patients.
AB  - Polyclonal sera from typhoid patients and a monoclonal antibody, mAb ATVi, which
      recognizes the capsular polysaccharide Vi antigen (ViCPS), were used to select
      for peptides that mimic the ViCPS by using a phage-displayed random 12-mer
      peptide library. Two major common mimotopes selected from the library carried the
      amino acid sequences TSHHDSHGLHRV and ENHSPVNIAHKL. Enzyme-linked immunosorbent
      assays (ELISAs) showed that these peptides carry mimotopes to ViCPS. Phage clones
      that contained the 12-mer peptides were also tested against pooled/individual
      typhoid patients' sera and found to have 3 to 5 times higher binding compared to
      normal sera. By using Phage-ELISA assays, the derived synthetic peptides,
      TSHHDSHGLHRV and ENHSPVNIAHKL, were tested against a monoclonal antibody mAb ATVi
      and over 2-fold difference in binding was found between these peptides and a
      control unrelated peptide, CTLTTKLYC. Inhibition of the mAb's binding to ViCPS
      indicated that the synthetic peptides successfully competed with the capsular
      polysaccharide for antibody binding.

PMID- 18037782
TI  - Direct comparison of the pharmacodynamics of four antifungal drugs in a mouse
      model of disseminated candidiasis using microbiological assays of serum drug
      concentrations.
AB  - The aim of this study was to compare the pharmacodynamics of the azole antifungal
      drugs fluconazole, itraconazole and ketoconazole, and the polyene antifungal
      amphotericin B, in a mouse model of disseminated Candida albicans infection. In
      order to directly compare effective serum concentrations of these antifungals,
      drug concentrations were assayed microbiologically by measuring inhibition of C.
      albicans mycelial growth (mMIC) in a mouse serum-based assay (serum antifungal
      titer). Efficacy in the mouse infection model was determined using an organ-based
      (kidney burden) endpoint. For all four drugs, the serum antifungal titers, 8 hr
      after administration of single doses of drugs at a range of drug concentrations,
      correlated closely with C. albicans kidney fungal burden in the mouse model. The
      results showed that determining serum antifungal titer may be used to accurately
      represent kidney fungal burden in a mouse model of disseminated candidiasis and
      allowed direct comparison of the pharmacodynamics of differing classes of
      antifungal drugs.

PMID- 18037783
TI  - Molecular cloning and characterization of all RND-type efflux transporters in
      Vibrio cholerae non-O1.
AB  - Resistance Nodulation cell Division (RND) efflux transporters are thought to be
      involved in mediating multidrug resistance in Gram-negative bacteria, including
      Vibrio cholerae non-O1. There are six operons for putative RND-type efflux
      transporters present in the chromosome of V. cholerae O1 including two operons,
      vexAB and vexCD, which had already been identified. All of the six operons were
      cloned from V. cholerae non-O1, NCTC4716 by the PCR method, introduced, and
      expressed in cells of drug hypersusceptible Escherichia coli KAM33 (DeltaacrAB,
      DeltaydhE). Only vexEF conferred elevated minimum inhibitory concentrations
      (MICs) of some antimicrobial agents in the E. coli cells. However, VexEF did not
      confer increased MIC of any drug tested in tolC-deficient E. coli KAM43 cells. On
      the other hand, when E. coli KAM43 was transformed with vexAB, vexCD or vexEF
      together with tolC(Vc) of V. cholerae NCTC4716, we observed elevated MICs of
      various antimicrobial agents. Among them, E. coli KAM43 expressing both VexEF and
      TolC(Vc) showed much higher MICs and much broader substrate specificity than the
      other two. We also observed ethidium efflux activity via VexEF-TolC(Vc), and the
      activity required Na(+). Thus, VexEF-TolC (Vc) is either a Na(+)-activated or a
      Na(+)-coupled transporter. To our knowledge, this is the first report on the
      requirement of Na(+) for an RND-type efflux transporter.

PMID- 18037784
TI  - Small red bean (azuki) sheds biologically active substances as a prerequisite
      step for germination, one of which displays the antiviral activity against the
      rabies virus infectivity and infections in culture.
AB  - When small red beans (azuki bean; Vigna angularis Ohwi et Ohashi) were soaked and
      warmed in water or saline, the beans began to absorb water to swell and exuded
      kinds of substances probably as a prerequisite step for seed germination. Such
      exudate fluids displayed strong antiviral activity against the rabies virus
      infections in culture. On the other hand, little anti-rabies activity was
      detected in the aqueous extracts from the red beans when tested soon after the
      extraction from powdered beans, while low titers of antiviral activity appeared
      gradually in the extracts during cold storage. In contrast, no antiviral activity
      was detected in the exudate fluids from non-colored azuki beans (white azuki),
      implicating that a certain anthocyanin-related substance is involved in the
      antiviral activity of red beans. Production of antiviral and cytotoxic activities
      were affected differently depending on the bean-soaking conditions. In addition,
      the antiviral activity resisted to 10 min-heating in boiling water, while the
      cytotoxicity was greatly weakened by the heating, suggesting that different
      substances are involved in the antiviral and cytotoxic activities. Further
      studies on the antiviral activity of the exudate fluids demonstrated that anti
      rabies activity of the bean exudates affected not only the very early phase of
      infection cycle, but the viral infectivity was also affected similarly,
      implicating a possible application of azuki bean exudate fluids to post-exposure
      treatment of rabid dog-bite injuries in combination with vaccination.

PMID- 18037785
TI  - Mode of infection of Hokkaido virus (Genus Hantavirus) among grey red-backed
      voles, Myodes rufocanus, in Hokkaido, Japan.
AB  - Hokkaido virus (HOKV) is a member of the genus Hantavirus, in the family
      Bunyaviridae. To investigate HOKV infection in the host Myodes rufocanus, the
      grey red-backed vole, 199 animals were captured at Tobetsu (October 2004 and July
      2005) and Nakagawa (October 2004) in Hokkaido, Japan, for detection of antibody,
      antigen, and viral RNA. In the surveys in Tobetsu (2004) and Nakagawa (2004),
      seropositive animals were detected at a frequency of 6.0% (5/84) and 10.4%
      (5/48), respectively. No seropositive animals were detected in Tobetsu in 2005.
      Seroprevalence in males in Tobetsu and Nakagawa in 2004 was 25% (1/4) and 45.5%
      (5/11), respectively, which was higher than in females, at 5.0% (4/80) and 0%
      (0/37), respectively (P<0.01). These results suggest that male animals play an
      important role in the maintenance of HOKV in M. rufocanus. Two females were
      seronegative but viral RNA-positive, indicating that these animals had acute
      infections before antibody was produced. Another five infected animals in
      Nakagawa were all male and had high levels of antibodies and viral RNA,
      suggesting that they had persistent infections. Viral RNA copies in organs of
      infected animals in Nakagawa were quantified by real-time polymerase chain
      reaction. Two acutely infected animals had > or = 10 times the number of RNA
      copies in their lungs compared to those of persistently infected animals. In most
      cases, lungs or spleen had the highest RNA copy number, regardless of infection
      status.

PMID- 18037786
TI  - Production of cross-reactive peptide antibodies against viral capsid proteins of
      human enterovirus B to apply diagnostic reagent.
AB  - The coxsackievirus group B (CVB) of the genus Enterovirus and the species human
      enterovirus B is a nonenveloped virus containing a single-stranded positive-sense
      RNA genome. Coxsackievirus has icosahedral symmetry and four capsid proteins,
      VP1, VP2, VP3, and VP4. Specific antibodies against each viral protein are
      prerequisites for various studies. In this study, we developed seven peptide
      derived antibodies directed against coxsackievirus VP1 (NO1-NO5), VP2 (B3), and
      VP3 (GL3). We developed a type-specific antibody (NO1) and broadly cross-reactive
      antibodies (NO3 and NO5) to VP1. Anti-VP2 and anti-VP3 antibodies (B3 and GL3,
      respectively) are also cross-reactive to human enterovirus B such as CVB and
      echoviruses. Their sensitivities and reactivities are likely to be better than
      those of the commercial VP1 monoclonal antibody (MAb). The dot-blot analysis also
      showed that NO5 against VP1 is able to detect less than 1 microg [2x10(6) plaque
      forming unit (pfu) of CVB3] of viruses, suggesting that it could be used to
      develop a diagnostic kit that can directly detect human enterovirus B. The
      antibodies produced here may allow us to undertake several studies, such as those
      involving viral trafficking, expression kinetics, and the roles of viral proteins
      in infection, and the development of diagnostic kits.

PMID- 18037787
TI  - Immune responses of mice to influenza subunit vaccine in combination with CIA07
      as an adjuvant.
AB  - CIA07 is an immunostimulatory agent composed of E. coli DNA fragments and
      modified LPS lacking the lipid A moiety. In this study, we investigated whether
      CIA07 promotes immune responses as an adjuvant to the influenza subunit vaccine.
      Balb/c mice were immunized intramuscularly once or twice at a 4-week interval
      with the trivalent influenza subunit vaccine antigen alone or in combination with
      CIA07 as adjuvant. Antigen-specific serum antibody titers and hemagglutination
      inhibition (HI) antibody titers were assessed. At 4 weeks after each
      immunization, the antigen-specific total serum IgG antibody titer in mice
      receiving CIA07 was 2 to 3 times higher than that in animals administered antigen
      alone (P<0.05). The CIA07-treated group additionally displayed higher HI antibody
      titers against each of the 3 vaccine strains, compared to the antigen group.
      Animals receiving antigen alone displayed barely detectable antigen-specific
      serum IgG2a antibody titers. In contrast, coadministration of CIA07 with antigen
      led to significantly enhanced IgG2a antibody responses, suggesting that CIA07
      stimulates a Th1-type immune response. Moreover, the CIA07-treated group
      displayed a marked increase in the number of interferon gamma-producing CD8(+) T
      cells in splenocytes. These data collectively demonstrate that CIA07 has the
      ability to induce both Th1-type cellular and Th2-type humoral immune responses to
      the influenza subunit vaccine, and support its potential as an effective adjuvant
      to the influenza vaccine.

PMID- 18037788
TI  - Orally administrated Lactobacillus gasseri TMC0356 and Lactobacillus GG
      alleviated nasal blockage of guinea pig with allergic rhinitis.
AB  - Lactobacillus GG (LGG) and L. gasseri TMC0356 (TMC0356) were investigated for
      their ability to alleviate nasal blockage associated with allergic rhinitis using
      a guinea pig model. The increases in sRaw at 10 min and 5 hr after the exposure
      of the nasal mucosa to OVA were significantly alleviated in the guinea pigs
      orally administrated with LGG and TMC0356 compared with those of the control
      (P<0.05 and P<0.01). The total numbers of leukocytes, particularly eosinophils
      and neutrophils from the nasal cavity lavage fluid, and the OVA-specific IgE
      concentration in the serum were also decreased in the guinea pigs orally
      administrated with LGG and TMC0356, although the decreases were not statistically
      significant. These results suggest that LGG and TMC0356 can alleviate antigen
      induced nasal blockage in earlyphase and late-phase inflammatory responses
      associated with allergic rhinitis.

PMID- 18037789
TI  - Dectin-1 is not required for the host defense to Cryptococcus neoformans.
AB  - Dectin-1 is known as a sole receptor for beta-glucan, a major cell wall component
      of fungal microorganisms. In the current study, we examined the role of this
      molecule in the host defense to Cryptococcus neoformans, an opportunistic fungal
      pathogen in AIDS patients. There was no significant difference in the clinical
      course and cytokine production between dectin-1 gene-deficient and control mice.
      These results indicate that dectin-1 is not likely essential for the development
      of host protective responses to C. neoformans.

PMID- 18037790
TI  - Novel functions of herbal medicines in dendritic cells: role of Amomi Semen in
      tumor immunity.
AB  - Dendritic cells (DCs) have a major role in regulating immune responses, including
      tumor immunity and peripheral tolerance. In the present study, we identified
      novel functions of herbal medicines in DCs by screening 99 herbal medicines, most
      of which are among the 210 Chinese medicines approved by the Ministry of Health,
      Labour, and Welfare, Japan. Ethanol extracts were prepared, and a murine
      epidermal-derived Langerhans cell line, XS106, was used to screen the 99 extracts
      by analyzing major histocompatibility complex (MHC) class II expression. Amomi
      Semen (amomum seed), Polyporus (polyporus sclerotium), and Plantaginis Semen
      (plantago seed) potently activated XS106 and were selected for further analysis.
      The effects of these extracts on bone marrow-derived DCs (BM-DCs) generated in
      vitro were then analyzed using surface phenotype (MHC class II, CD80, and CD86)
      and interleukin (IL)-12p70 production as indicators. BM-DCs treated with Amomi
      Semen extract exhibited activated phenotypes and secreted IL-12p70. The
      activation level was similar to that induced by lipopolysaccharides. Finally, an
      E.G7-OVA tumor model (E.L4-OVA transfectant) was used to examine the anti-tumor
      effects of Amomi Semen extract. Vaccination of mice with a subcutaneous injection
      of BM-DCs treated with Amomi Semen extract and OVA peptide significantly
      inhibited the growth of tumor cells and prolonged survival time compared to
      controls. Furthermore, therapeutic effects were observed on established tumors.
      The inhibition rates for both the prophylactic and therapeutic protocols were
      comparable to those of lipopolysaccharides. These results indicate that Amomi
      Semen extract potently activate DCs and is potentially useful for DC vaccination.

PMID- 18037791
TI  - T-helper (Th)1/Th2 imbalance in the peripheral blood of dogs with malignant
      tumor.
AB  - T helper type 1 cell (Th1)/Th2 imbalance has been observed in a variety of
      pathological conditions, including malignant diseases. We evaluated the Th1/Th2
      in peripheral blood Th cells by means of intracytoplasmic cytokine analysis in 11
      dogs with advanced malignant tumor; four of them showed metastatic tumor. The
      percentage of Th1 was significantly lower and the percentage of Th2 was
      significantly higher in diseased dogs compared to healthy dogs. The percentage of
      Th1 in three patients with metastatic tumor was significantly lower than that in
      the patients with non-metastatic tumor. We conclude that the Th1/Th2 balance was
      polarized to Th2 in dogs with cancer.

PMID- 18037792
TI  - Improved geometric distortion in coronal diffusion-weighted and diffusion tensor
      imaging using a whole-brain isotropic-voxel acquisition technique at 3 Tesla.
AB  - PURPOSE: We used a whole-brain, isotropic-voxel acquisition technique to improve
      the geometric distortion in diffusion-weighted (DWI) and diffusion tensor imaging
      (DTI) in coronal directions, which is remarkable at high magnetic fields.
      MATERIALS AND METHODS: We performed magnetic resonance imaging of 17 healthy
      volunteers using a 3T scanner and obtained coronal DWI/DTI as well as coronal
      images that were reformatted from isotropic volume data acquired by 1.6-mm-thick
      axial DWI/DTI. We visually evaluated the degree of image distortion and
      quantitated the findings by co-registration analysis. RESULTS: In-plane geometric
      distortions in coronal DWI/DTI, particularly at the frontal base and medial
      temporal lobe, were dramatically diminished when the isotropic-voxel acquisition
      technique was used. Quantitative measurement revealed a reduction in areas of
      misregistration, but not their absence, in reformatted coronal images, mainly
      because of distortion in the anteroposterior direction in the source images.
      CONCLUSION: The isotropic-voxel DWI/DTI technique enabled acquisition of coronal
      images that represented anatomical details accurately with permissible spatial
      distortion while maintaining spatial resolution, even at 3T.

PMID- 18037793
TI  - Standardizing display conditions of diffusion-weighted images using concurrent b0
      images: a multi-vendor multi-institutional study.
AB  - PURPOSE: To establish a practical method that uses concurrent b0 images to
      standardize the display conditions for diffusion-weighted images (DWI) that vary
      among institutions and interpreters. METHOD: Using identical parameters, we
      obtained DWI for 12 healthy volunteers at 4 institutions using 4 MRI scanners
      from 3 vendors. Three operators manually set the window width for the images
      equal to the signal intensity of the normal-appearing thalamus on b0 images and
      set the window level at half and then exported the images to 8-bit gray-scale
      images. We calculated the mean pixel values of the brain objects in the images
      and examined the variation among scanners, operators, and subjects. RESULT:
      Following our method, the DWI of the 12 subjects obtained using the 4 different
      scanners had nearly identical contrast and brightness. The mean pixel values of
      the brain on the exported images among the operators and subjects were not
      significantly different, but we found a slight, significant difference among the
      scanners. CONCLUSION: Determining DWI display conditions by using b0 images is a
      simple and practical method to standardize window width and level for evaluating
      diffusion abnormalities and decreasing variation among institutions and
      operators.

PMID- 18037794
TI  - Imaging of a large collection of human embryo using a super-parallel MR
      microscope.
AB  - Using 4 and 8-channel super-parallel magnetic resonance (MR) microscopes with a
      horizontal bore 2.34T superconducting magnet developed for 3-dimensional MR
      microscopy of the large Kyoto Collection of Human Embryos, we acquired T(1)
      weighted 3D images of 1204 embryos at a spatial resolution of (40 microm)(3) to
      (150 microm)(3) in about 2 years. Similarity of image contrast between the T(1)
      weighted images and stained anatomical sections indicated that T(1)-weighted 3D
      images could be used for an anatomical 3D image database for human embryology.

PMID- 18037795
TI  - Whole-body MRI for detecting metastatic bone tumor: diagnostic value of diffusion
      weighted images.
AB  - PURPOSE: We assessed the diagnostic value of whole body magnetic resonance (MR)
      imaging (WB-MRI) using diffusion-weighted images (DWI) for detecting bone
      metastasis and compared it with that of skeletal scintigraphy (SS). MATERIALS AND
      METHODS: Thirty patients with malignancies (breast cancer, 17 patients; prostate
      cancer, 9; and one patient each, thyroid cancer, liposarcoma, leiomyosarcoma, and
      extraskeletal Ewing sarcoma) underwent both WB-MRI and SS to detect bone
      metastasis. All patients were followed more than 6 months by MR imaging, SS, or
      computed tomographic (CT) examination. For WB-MRI, patients were placed in feet
      first supine position with table-top extender and quadrature body coil. We
      acquired DWI (axial plane from lower neck to proximal femur) (single shot short
      TI inversion-recovery [STIR]: repetition time [TR] 6243/echo time [TE]
      59/inversion time [TI] 180 ms; b value: 600 s/mm(2); 5-mm slice thickness; 112 x
      112 matrix), T(1)-weighted fast spin echo (T(1)WI), and STIR (sagittal plane of
      total spine images and coronal plane of whole body images) images. Four blinded
      readers independently and separately interpreted images of combined MR sequences
      of T(1)WI+STIR (session 1) and T(1)WI+STIR+DWI (session 2). RESULTS: In 10 of 30
      patients, we detected a total of 52 metastatic bone lesions; in the other 20,
      follow-up examinations confirmed no metastatic bone lesions. For these 52
      lesions, for session 2, the mean sensitivity was 96% and the positive predictive
      value (PPV) was 98%. Those values were superior to those of session 1
      (sensitivity: 88%; PPV: 95%) and those of SS (sensitivity: 96%; PPV: 94%).
      CONCLUSION: WB-MRI that included DWI was useful for detecting bone metastasis.

PMID- 18037796
TI  - Advances in coronary MRA from vessel wall to whole heart imaging.
AB  - Since its introduction, magnetic resonance (MR) imaging has undergone continued
      technical and methodological development and found numerous practical clinical
      applications. Cardiac MR imaging is one of the more sophisticated applications of
      MR, owing to the inherent presence of flow and motion and specific anatomy. Among
      the different categories of cardiac MR imaging, coronary MR angiography (MRA)
      places particularly high demands on planning, spatial resolution, high signal-to
      noise ratio (SNR), and precise cardiac and respiratory motion correction.
      However, recent advances in hardware, MR sequences, and motion detection
      techniques have made it possible to perform coronary MRA that includes volumetric
      acquisition of the entire heart as well as imaging of the vessel walls on a
      submillimeter scale within a clinically acceptable scan time. We discuss from a
      technical perspective some of the milestones leading to the current state of
      coronary MR imaging and outline recent developments that will further advance
      coronary MR imaging. We discuss planning procedure, contrast preparation
      mechanisms and MR sequences, motion correction, high-resolution coronary artery
      and vessel wall imaging, and fast volumetric scanning techniques. Although MR
      imaging has certain limitations in providing simultaneous speed, resolution, and
      high SNR, it nonetheless offers a dedicated scanning procedure that addresses
      most clinically relevant questions in the diagnosis of ischemic heart disease.

PMID- 18037797
TI  - Measuring visceral fat with water-selective suppression methods (SPIR, SPAIR) in
      patients with metabolic syndrome.
AB  - We attempted to measure the area and volume of visceral fat using magnetic
      resonance (MR) imaging to avoid radiation exposure. We used water suppression
      spectral attenuation with inversion recovery (WS-SPAIR) as prepulses and
      conducted T(1) high-resolution isotropic volume examination (THRIVE). Image
      processing software can be used to estimate the area and volume of fat and
      separate the fat and water signals at a visually optimal threshold in the MR
      image, which requires contrast enhancement between intestinal contents and
      visceral fat. In 14 volunteers, we evaluated WS-SPAIR and water suppression
      spectral presaturation with inversion recovery (WS-SPIR) with respect to the
      relationship between the flip angle of THRIVE and signal contrast. We used flip
      angles of 5 degrees, 10 degrees, and 20 degrees. The minimum threshold that
      allowed exclusion of intestinal contents from the masked region was determined
      for each technique. The volume and area of the masked region, which included
      subcutaneous fat, were measured at the umbilicus level. Both volume and area
      increased with a smaller flip angle. The masked region was larger with WS-SPIR
      THRIVE (flip angle 5 degrees ). The size of the masked region was determined
      according to the minimum threshold that allowed exclusion of the intestinal
      contents from the masked region, expressing the contrast between the intestinal
      contents and fat in a relative manner. It was speculated that by separating the
      signals at the threshold, WS-SPIR-THRIVE (flip angle 5 degrees) was a more
      suitable technique for measuring the area and volume of visceral fat.

PMID- 18037798
TI  - Sensitivity of an eight-element phased array coil in 3 Tesla MR imaging: a basic
      analysis.
AB  - PURPOSE: To evaluate the performance advantages of an 8-element phased array head
      coil (8 ch coil) over a conventional quadrature-type birdcage head coil (QD coil)
      with regard to the signal-to-noise ratio (SNR) and image uniformity in 3 Tesla
      magnetic resonance (MR) imaging. MATERIALS AND METHODS: We scanned a phantom
      filled with silicon oil using an 8 ch coil and a QD coil in a 3T MR imaging
      system and compared the SNR and image uniformity obtained from T(1)-weighted spin
      echo (SE) images and T(2)-weighted fast SE images between the 2 coils. We also
      visually evaluated images from 4 healthy volunteers. RESULTS: The SNR with the 8
      ch coil was approximately twice that with the QD coil in the region of interest
      (ROI), which was set as 75% of the area in the center of the phantom images. With
      regard to the spatial variation of sensitivity, the SNR with the 8 ch coil was
      lower at the center of the images than at the periphery, whereas the SNR with the
      QD coil exhibited an inverse pattern. At the center of the images with the 8 ch
      coil, the SNR was somewhat lower, and that distribution was relatively flat
      compared to that in the periphery. Image uniformity varied less with the 8 ch
      coil than with the QD coil on both imaging sequences. CONCLUSION: The 8 ch phased
      array coil was useful for obtaining high quality 3T images because of its higher
      SNR and improved image uniformity than those obtained with conventional
      quadrature-type birdcage head coil.

PMID- 18037799
TI  - The "morning glory sign" may lead to false impression according to slice angle.

PMID- 18037801
TI  - Characteristics of helmet or knit cap use in head injury of snowboarders.
AB  - The rate of head injury is 1.86-6 times higher for snowboarding than for skiing.
      Detailed data about the usefulness of a helmet or knit cap for protecting against
      serious head injuries have not been reported. The present study evaluated the use
      of a helmet or knit cap for preventing head injuries. Questionnaire data were
      collected from 1,190 consecutive patients in a hospital during the 1999/2000
      2002/2003 winter seasons at Uonuma ski resort, Niigata, Japan. Patients were
      divided into the helmet, knit cap, and no cap groups. Upper technical level was
      highest and jumping as the cause of injury was most frequent in the helmet group.
      After adjustment for other confounders, there was a significant negative
      association between the occurrence of serious head injury during snowboarding and
      female sex (adjusted odds ratio 0.55, 95% confidence interval 0.421-0.718, p <
      0.0001) and a significant positive association between serious head injury and
      jumping (adjusted odds ratio 2.25, 95% confidence interval 1.48-3.43, p =
      0.0001). Among snowboarding maneuvers, only jumping showed a significant negative
      association between wearing of a helmet or knit cap and the occurrence of serious
      head injury (p = 0.036). Snowboarders who wear helmets might attempt dangerous
      maneuvers causing injuries. Wearing of a helmet or knit cap protected against
      serious head injuries on jumping. Every snowboarder should wear a helmet or knit
      cap on jumping to prevent head injury.

PMID- 18037802
TI  - Risk factors for perioperative cardiac complications after lumbar fusion surgery.
AB  - Cardiac complication is a leading cause of death in the perioperative period
      after non-cardiac surgery. The present study retrospectively investigated
      perioperative cardiac complications after spinal fusion surgery in 901
      consecutive adult patients who underwent fusion surgery in the lumbar spine from
      January 2005 to December 2006. Cardiac complications developed in seven patients
      (0.8%), four males and three females aged 62 to 75 years (mean 66.6 years), in
      the perioperative period (myocardial infarction in 6 and angina pectoris in 1).
      Cardiac complications developed after mini-open transforaminal lumbar interbody
      fusion in four patients and after anterior lumbar interbody fusion in three. No
      patient had any symptoms related to cardiac disease before surgery. Common
      features were age over 60 years, a medical history of hypertension and/or
      diabetes mellitus, and presence of calcified atherosclerosis of the abdominal
      aorta and/or common iliac arteries. Five patients improved after conservative
      medical treatment in an intensive care unit. Percutaneous transluminal coronary
      angioplasty was performed in one patient and coronary artery bypass graft surgery
      in one. The possibility of perioperative cardiac complications should be
      considered before lumbar fusion surgery, especially in elderly patients with
      hypertension and/or diabetes mellitus, and calcified atherosclerosis of the
      abdominal aorta and/or common iliac arteries.

PMID- 18037803
TI  - Splitting of the optic nerve associated with ruptured anterior communicating
      artery aneurysm.
AB  - A 52-year-old man presented with an anterior communicating artery aneurysm
      associated with splitting, penetration, and visual symptoms of the optic nerve
      and manifesting as sudden onset of severe headache. Angiography disclosed a 10-mm
      anterior communicating artery aneurysm projecting supero-posteriorly, and
      operative findings revealed unexpected splitting of the optic nerve. Moreover,
      the optic nerve was not in direct contact with the aneurysm fundus. Splitting of
      the optic nerve without the presence of a penetrating aneurysm is extremely rare.
      The pathogenesis of optic nerve penetration may involve congenital fenestration
      of the optic nerve.

PMID- 18037804
TI  - Development of unusual collateral channel from the posterior meningeal artery
      after endovascular proximal occlusion of the posterior inferior cerebellar
      artery.
AB  - A 38-year-old man presented with a dissecting aneurysm of the left proximal
      posterior inferior cerebellar artery (PICA) manifesting as Wallenberg's syndrome.
      The patient was treated by endovascular occlusion of the aneurysm and parent
      artery. Immediately after the treatment, the PICA territory was supplied by
      collateral circulation via the ipsilateral anterior inferior cerebellar artery.
      Seven days later, endogenous revascularization of the distal PICA territory had
      occurred via collateral circulation from the posterior meningeal artery (PMA).
      This unusual collateral circulation was thought to occur through a pre-existing
      anastomotic channel between the primitive vessels of the PICA and the PMA during
      subclinical hypoperfusion of the distal PICA territory. This unusual case
      demonstrates the potential for delayed development of collateral circulation from
      the PMA to the PICA territory.

PMID- 18037805
TI  - Intraosseous cavernous hemangioma of the frontal bone.
AB  - A 32-year-old man presented with a primary intraosseous cavernous hemangioma
      manifesting as a small painless swelling of the right forehead. Radiography
      revealed a radiolucent osteolytic lesion in the right frontal region. Bone window
      computed tomography demonstrated a 1.5 cm mass between the outer and inner tables
      just lateral to the right frontal sinus. The outer and inner tables were thin and
      partially defective, but without bone fracture. Magnetic resonance imaging
      revealed a small mass lesion with bone erosion of the posterior table of the
      frontal bone. Preoperative examination yielded no final diagnosis. En bloc
      resection was performed. The histological diagnosis was primary intraosseous
      cavernous hemangioma. Total resection is recommended for definitive diagnosis of
      intraosseous tumor.

PMID- 18037806
TI  - Association of cavernous malformation within vestibular schwannoma:
      immunohistochemical analysis of matrix metalloproteinase-2 and -9.
AB  - A 65-year-old man presented with a rare case of cavernous malformation with
      hemorrhage located within vestibular schwannoma. He had suffered hearing
      impairment for 20 years, and was admitted to our hospital with vertigo and ataxic
      gait. Neurological examination revealed hearing loss, facial nerve paresis, and
      left cerebellar ataxia. Magnetic resonance imaging demonstrated a left vestibular
      schwannoma 35 mm in diameter, as well as a heterogeneous area associated with
      hypointense rim within the tumor, indicating intratumoral hemorrhage. Subtotal
      removal of the tumor together with the fibrously encapsulated hematoma was
      performed through a left retrosigmoid craniotomy. Histological examination of the
      surgical specimen revealed cavernous malformation within vestibular schwannoma.
      Immunohistochemistry for matrix metalloproteinase (MMP)-2 and -9, and tissue
      inhibitors of metalloproteinase-2 showed strong expression in the endothelial
      cells of the cavernous malformation, but not in the interstitial structures. His
      symptoms significantly improved after surgery and he underwent gamma-knife
      therapy for the residual tumor. Cavernous malformations may show dynamic
      characteristics such as repeated hemorrhage and de novo formation. MMP-2 and -9,
      which are implicated in angiogenesis and hemorrhage, may be upregulated in such
      tumors.

PMID- 18037807
TI  - Intradural extramedullary ganglioneuroma associated with multiple hamartoma
      syndrome.
AB  - A 51-year-old woman presented with a rare completely intradural and
      extramedullary spinal ganglioneuroma associated with multiple hamartoma syndrome
      and manifesting as complaints of neck pain and dizziness persisting for 8 months.
      Magnetic resonance imaging of the spinal cord revealed an intradural
      extramedullary lesion at the C1 level. She underwent right suboccipital
      craniectomy and C1-2 hemilaminectomy to remove the tumor. Histological
      examination confirmed ganglioneuroma. She also suffered from multiple facial
      trichilemmomas, thyroid goiter, multiple polyposis of the gastrointestinal tract,
      and pulmonary hamartoma indicating multiple hamartoma syndrome. These benign
      neoplasms were treated conservatively.

PMID- 18037808
TI  - Magnetic resonance imaging of brain abscess with hemorrhage: implications for the
      mechanism of hemorrhage.
AB  - A 68-year-old woman presented with an extremely rare brain abscess associated
      with old and acute hemorrhages manifesting as gradual onset of symptoms of
      headache and fever. Magnetic resonance imaging clearly visualized the hemorrhage
      as heterogeneously hyperintense on diffusion-weighted imaging, concentric hypo
      isointense on T(1)-weighted imaging, and homogeneously hyperintense with a
      hypointense rim on T(2)(*)-weighted imaging. T(1)-weighted imaging with contrast
      medium revealed a well-enhanced cyst wall. In spite of treatment with
      antibiotics, the neurological status of the patient deteriorated due to expansion
      of the abscess and perifocal edema. Needle aspiration of the cyst yielded bloody
      purulent fluid. The magnetic resonance imaging findings indicate that
      neovascularization of the cyst wall is involved in the mechanism of hemorrhage in
      brain abscess. Careful follow-up examinations are recommended in patients with
      brain abscess to detect warning signs of neurological deterioration.

PMID- 18037809
TI  - Closed-lip schizencephaly around the central sulcus with intractable epilepsy
      treated by peri-lesional focus resection.
AB  - A 24-year-old man presented with closed-lip schizencephaly around the right
      central sulcus manifesting as an 11-year history of intractable epilepsy. Mild
      motor paresis in the left extremities and mental retardation were observed. Tonic
      posture with bilateral facial tonic contraction was asymmetrical, predominantly
      in the left extremities. Magnetic resonance imaging demonstrated closed-lip
      schizencephaly around the right central sulcus. The epileptogenic zone was
      determined in the supplementary motor area, and premotor and primary sensorimotor
      cortices using invasive recordings. As the thickened cortex was considered
      functional, corticectomy of the supplementary motor area and premotor area was
      performed, preserving the primary sensorimotor area. Histological examination
      revealed marked cortico-subcortical gliosis, particularly in the medial part of
      the resection. Asymmetrical tonic postural seizure disappeared completely after
      surgery. Medically intractable epilepsy with schizencephaly represents a
      considerable challenge in epilepsy surgery. Partial corticectomy adjacent to the
      thickened cortex was effective for seizure control in a patient with closed-lip
      schizencephaly around the central sulcus.

PMID- 18037810
TI  - Simple new method for making a rat carotid artery post-angioplasty stenosis
      model.
AB  - A simple new method for making a rat post-angioplasty stenosis model was
      developed using a single-lumen compliant balloon catheter/guidewire system and no
      special diet. This technique was applied to 10 9-week-old Wistar rats fed a
      normal diet. The catheter/guidewire system was inserted from the external carotid
      artery and advanced retrogradely into the common carotid artery. The balloon was
      inflated six times with rotation through 60 degrees . After angioplasty, the
      external carotid artery was ligated. Homogeneous stenoses due to intimal
      hyperplasia were demonstrated in cross sections of all cases. This simple and
      gentle method allows an easily reproducible post-angioplasty stenosis model.

PMID- 18037812
TI  - Adjuvant endobronchial amphotericin B for refractory invasive pulmonary
      aspergillosis: evidence is scarce but promise does exist.

PMID- 18037813
TI  - Direct hemoperfusion with a cytokine-adsorbing device for the treatment of
      persistent or severe hypercytokinemia: a pilot study.
AB  - BACKGROUND/AIMS: Cytokine overproduction has been noted during the aggravation of
      clinical conditions. Countermeasures to control hypercytokinemia are therefore
      important in critical care. We investigated the clinical efficacy of
      hemoadsorption therapy using a new cytokine-adsorbing device in critically ill
      patients with persistent or severe hypercytokinemia. METHODS: Direct
      hemoperfusion using the CYT-860, a cytokine-adsorber column (CYT-860-DHP), was
      performed in critically ill patients with hypercytokinemia. To evaluate the
      efficacy of CYT-860-DHP, changes in pathological and clinical parameters were
      examined. RESULTS: Seven patients with hypercytokinemia and a SOFA score of > or
      = 5 underwent CYT-860-DHP treatment. Four patients survived 28 days after CYT-860
      DHP treatment. Significant decreases in blood levels of cytokines were observed.
      PaO2/F(I)O2 improved significantly. CONCLUSION: The possibility that CYT-860-DHP
      treatment can reduce blood cytokine levels and thereby improve the general
      condition of patients was suggested. These findings warrant the initiation of a
      prospective randomized trial to evaluate the clinical efficacy of CYT-860-DHP
      treatment.

PMID- 18037814
TI  - Education and use of dementia drugs: a register-based study of over 600,000 older
      people.
AB  - BACKGROUND/AIMS: Low education has been shown to be a risk factor for dementia.
      However, little is known about the association between educational level and
      dementia drugs. METHODS: We conducted a register-based study in Sweden of 645,973
      people aged 75-89 years. Data on age, sex, type of residential area
      (urban/rural), dispensed drugs and education were analyzed from people aged 75-89
      years registered in the Swedish Prescribed Drug Register during July to October
      2005. The 3 main outcome measures were dispensed dementia drugs, cholinesterase
      inhibitors (donepezil, rivastigmine and galantamine) and memantine. RESULTS:
      Dementia drugs were used by 3% of the study population, cholinesterase inhibitors
      by almost 3% and memantine by 0.4%. High education was associated with dementia
      drugs (OR: 1.26; 95% CI: 1.19-1.34 for >or=15 years of education compared with
      <or=9 years), cholinesterase inhibitors (OR: 1.25; 95% CI: 1.17-1.33 for >or=15
      years of education compared with <or=9 years) and, especially, memantine (OR:
      1.46; 95% CI: 1.26-1.68 for >or=15 years of education compared with <or=9 years),
      after adjustment for age, sex, type of residential area and number of dispensed
      drugs. CONCLUSION: The results indicate that there may be inequalities in the use
      of dementia drugs among elderly Swedes. Future research is required to explain
      why educational level has the opposite relationship to dementia drugs than to
      dementia diagnosis.

PMID- 18037811
TI  - Genetic predisposition to respiratory diseases: infiltrative lung diseases.
AB  - The availability of high-throughput genotyping and large collaborative clinical
      networks creating well-characterized patient populations with DNA repositories
      has facilitated genome-wide scans and candidate gene studies to identify
      susceptibility alleles for the development of interstitial lung disease. The
      association of pulmonary fibrosis with rare inherited disorders, and the variable
      susceptibility of inbred mouse strains to this disease indicate that pulmonary
      fibrosis is determined by genetic factors. Sarcoidosis represents a complex
      disease with racial and ethnic differences in disease prevalence, and evidence of
      familial clustering. Familial aggregation of sarcoidosis from 'A Case-Control
      Etiologic Study of Sarcoidosis' (ACCESS) reveals a familial odds ratio (OR) of
      sarcoidosis of 5.8 (95% CI 2.1-15.9) for sibs and 3.8 (95% CI 1.2-11.3) for
      parents. Several HLA class II alleles have been associated with either increased
      or decreased risk of sarcoidosis, and results vary depending on study populations
      of different ethnicity. Genome-wide screening has conclusively identified linkage
      to chromosome 5q11and the development of sarcoidosis, and HLA genes and BTNL2 are
      susceptibility genes located in this region. Familial aggregation of idiopathic
      interstitial pneumonia (IIP) has been established by several groups, and a large
      US-based study suggests autosomal dominant inheritance with reduced penetrance;
      furthermore, cigarette smoking was associated with affection status among
      siblings (OR = 3.6, 95% CI 1.3-9.8, p = 0.01). Families demonstrate more than one
      type of IIP, suggesting various subtypes of IIP may share a common pathogenesis.
      Genome-wide linkage scans in familial interstitial pneumonia demonstrate linkage
      to chromosomes 4, 5 and 11. Candidate gene studies indicate that surfactant
      protein C and telomerase are susceptibility genes for the development of
      pulmonary fibrosis. Future challenges include determining how multiple
      susceptibility alleles interact with each other and environmental factors
      resulting in disease risk and multiple phenotypes, and determining the mechanism
      of action and cellular pathways involving susceptibility alleles. Further insight
      into these areas may lead to new therapeutic interventions.

PMID- 18037815
TI  - Monocytic, Th1 and th2 cytokine alterations in the pathophysiology of
      schizophrenia.
AB  - A growing body of evidence suggests that changes in the serum levels and cellular
      production of various cytokines are associated with the immunological
      abnormalities of schizophrenia. Several studies have examined alterations in T
      helper type 1 (Th1) and T helper type 2 (Th2) cytokines in schizophrenia. We
      explored monocytic, Th1 and Th2 cytokines in 43 schizophrenia patients and 50
      normal controls. The mitogen-induced production of tumor necrosis factor alpha
      (TNF-alpha), interleukin 6 (IL-6), IL-4, gamma-interferon (IFN-gamma) and IL-2
      was measured with enzyme-linked immunosorbent assays before and after
      antipsychotic treatment. IL-6 and TNF-alpha production by schizophrenic patients
      was significantly higher than by normal controls, while IL-2, IL-4 and IFN-gamma
      production was significantly lower in schizophrenic patients. After 6 weeks of
      antipsychotic treatment, IL-6 and TNF-alpha production was significantly
      decreased, while IL-4, IFN-gamma and IL-2 productions were not significantly
      changed. Our results suggest that increased monocytic cytokines and decreased Th1
      and Th2 cytokines may be associated with the immunopathogenesis of acute
      psychotic schizophrenia, and that antipsychotics may play an important role in
      immune response by decreasing elevated monocytic cytokines.

PMID- 18037816
TI  - Nicotine effects on mismatch negativity in nonsmoking schizophrenic patients.
AB  - BACKGROUND: The goal of the present study is to identify the effect of nicotine
      on auditory automatic processing, as reflected by mismatch negativity (MMN), in
      nonsmoking schizophrenic patients. METHODS: Ten nonsmoking schizophrenic patients
      and 10 healthy volunteers underwent a reference session and 2 test sessions. The
      test sessions involved administration of a placebo patch and a nicotine skin
      patch, which were counterbalanced. Nicotine was administered transdermally under
      controlled dosage. RESULTS: Nicotine administration shortened the MMN latencies
      (at Fz on nicotine/placebo: 134.8 +/- 5.7/157.6 +/- 6.4 ms) in healthy
      volunteers. In contrast, there were no significant differences in MMN latencies
      in schizophrenic patients (169.6 +/- 5.7/165.0 +/- 6.4 ms). CONCLUSION: Nicotine
      activates and accelerates preattentive and automatic processing in healthy
      controls, whereas there were no such effects observed in nonsmoking patients. The
      impaired MMN response to nicotine administration in nonsmoking schizophrenic
      patients may be attributed to low nicotinic receptor function, implicated in
      dysregulation of the glutamatergic system.

PMID- 18037817
TI  - Differential antidepressant symptom efficacy: placebo-controlled comparisons of
      duloxetine and SSRIs (fluoxetine, paroxetine, escitalopram).
AB  - OBJECTIVE: To test the hypothesis that in patients with major depressive disorder
      (MDD), the response for specific Hamilton Depression Rating Scale items will
      differ for duloxetine compared with selective serotonin reuptake inhibitors
      (SSRIs) and that patterns of response will differ based on symptom severity at
      baseline. METHOD: Data were pooled from all Lilly-sponsored clinical trials where
      duloxetine was compared with placebo and an SSRI in patients with MDD: 7
      randomized, double-blind, fixed-dose, 8-week studies of duloxetine (n = 1,133)
      versus SSRI (n = 689) versus placebo (n = 641). Duloxetine doses were 40, 60, 80
      and 120 mg/day. SSRI doses were 10 mg/day (escitalopram) and 20 mg/day
      (fluoxetine and paroxetine). RESULTS: Compared to SSRI-treated patients,
      duloxetine-treated patients had a significantly greater (p < or = 0.05) reduction
      in the 17-item Hamilton Depression Rating Scale (HAMD17) total score and HAMD17
      items of work and activities, psychomotor retardation, genital symptoms and
      hypochondriasis. Differences favoring the SSRIs approached significance for
      middle insomnia (p = 0.057) and late insomnia (p = 0.06), with effect sizes at
      least twice the magnitude of the corresponding effect sizes for duloxetine.
      Similarly, the advantage for duloxetine versus the SSRIs approached significance
      for general somatic symptoms (p = 0.056), with an effect size twice that observed
      for the SSRIs. The HAMD17 total score difference was driven mostly by patients
      with lower baseline MDD severity (HAMD17 total score < or = 19), where the HAMD17
      effect size advantage for duloxetine over combined SSRIs was statistically
      significant (p = 0.031). CONCLUSION: Potentially important differences in symptom
      response patterns were found between duloxetine and the combined SSRIs depending
      on symptom severity, and different HAMD17 items responded differently to
      duloxetine compared with SSRIs. Understanding these differences may be useful in
      tailoring antidepressant therapy for individual patients.

PMID- 18037818
TI  - Seasonality of suicide: relationship with the reason for suicide.
AB  - AIMS: This study set out to test the hypothesis that the suicides that can be
      attributed to a psychiatric illness show a higher seasonality than the suicides
      due to any other reason. METHODS: All the suicides registered in Italy from 1984
      to 2000 (57,796 deaths by suicide: males = 41,741, yearly rate = 11.3 per
      100,000; females = 16,055, yearly rate = 4.0 per 100,000) were analyzed with
      circular statistic techniques, based on the maximization of mean vector length
      method and on the Rayleigh test. RESULTS: The suicides clearly attributed to a
      psychiatric illness were 35.0% among males and 51.3% among females. An economic
      reason for suicide was more frequently found among males; somatic illness or
      sentimental reasons were equally distributed in both sexes. The suicides
      attributable to a psychiatric illness showed a significantly higher seasonal
      unevenness than the suicides attributable to somatic illness and to sentimental
      or economic reasons. CONCLUSIONS: The main drawback of this study is that
      psychiatric diagnoses were not formally assessed by a forensic specialist.
      However, it succeeded in showing that the dynamics of suicidal behaviour are not
      unilineal: suicides due to psychiatric or somatic illness mainly happen in
      spring/summer and those due to economic difficulties mainly in December. Patients
      with psychiatric and/or somatic illness should be more carefully followed in
      spring/summer.

PMID- 18037819
TI  - Serum BDNF levels in suicide attempters related to psychosocial stressors: a
      comparative study with depression.
AB  - Although many studies have examined the neurobiological aspects of suicide, the
      molecular mechanisms and pathophysiologic mechanisms associated with suicide
      remain unclear. In this study, it is aimed to investigate whether there is a
      difference in serum brain-derived neurotrophic factor (BDNF) levels among suicide
      attempters without a major psychiatric disorder, compared to major depressive
      disorder patients and healthy subjects. It was undertaken with the hypothesis
      that suicide per se lowers serum BDNF levels, since it is a source of stress. The
      study was carried out in Celal Bayar University Hospital, Manisa, Turkey. Ten
      suicide attempters, 24 patients with major depressive disorder and 26 subjects
      without any psychiatric diagnosis and any psychiatric treatment were included in
      the study. All subjects were asked to give their written consent. Blood samples
      were collected at the baseline. Serum BDNF was kept at -70 degrees C before
      testing, and assayed with an ELISA kit (Promega; Madison, Wisc., USA) after
      dilution with the block and sample solution provided with the kit. The data were
      subjected to the Kruskal-Wallis test for nonparametric analysis of variance. Mean
      serum BDNF levels were significantly lower in the suicide group (21.2 +/- 12.4
      ng/ml) and the major depressive disorder group (21.2 +/- 11.3 ng/ml) than the
      control group (31.4 +/- 8.8 ng/ml; p = 0.004). These results suggest that BDNF
      may play an important role in the neurobiology of suicidal behavior. BDNF levels
      may be a biological marker for suicidal behavior. To investigate the role of BDNF
      in suicide, further studies with a wider sample size and a variety of psychiatric
      diagnoses accompanying suicide attempt are needed.

PMID- 18037820
TI  - Access to dental services in Scotland: an analysis of dentist-population ratios.
AB  - OBJECTIVE: To assess inequalities in the availability of NHS dental services
      between Health Boards in Scotland. STUDY DESIGN: Postal questionnaire survey of
      all dentists (n = 2,852) registered with the General Dental Council at an address
      in Scotland. METHODS: Data obtained on NHS working hours were used to model
      dentist to population (D/P) ratios and primary care D/P ratios corrected for part
      time working, variation in service productivity and the provision of private
      services. RESULTS: A total of 2,134 completed questionnaires (74.8%) were
      received. There was a wide variation in D/P ratios between Health Boards.
      Dumfries & Galloway and Grampian had the lowest, and Tayside and Greater Glasgow
      the highest D/P ratios, irrespective of method of calculation. The corrected D/P
      ratios for the other Health Boards were more similar than was suggested by the
      simple ratios of registered dentists to population size. CONCLUSIONS: There was
      considerable variation in the availability of NHS dental practitioners between
      Health Boards. Simple ratios of registered dentists to population size can mask
      the true availability of specific dental services such as NHS dental care.

PMID- 18037821
TI  - Relationship between the presence of tonsilloliths and halitosis in patients with
      chronic caseous tonsillitis.
AB  - OBJECTIVE: To study the volatile sulphur compounds (VSC) halitometry profile in a
      population with chronic caseous tonsillitis (CCT) and halitosis and to evaluate
      the relationship between the presence of a tonsillolith and abnormal halitometry
      in this population. DESIGN: Clinical prospective non-randomised study. SUBJECTS
      AND METHODS: Forty-nine patients with halitosis and CCT, 17 male (35%) and 32
      female (65%), were selected among patients referred for CO(2) laser cryptolysis.
      Anamnesis, physical examination and VSC halitometry were carried out. Halitometry
      values less than 150 ppb of VSC were considered normal. RESULTS: Patients were
      divided in two groups: Group A - normal halitometry (41 patients - 83.7%) and
      Group B - abnormal halitometry (8 patients - 16.3%). Halitometry results in Group
      B were 5.2 times (429%) higher than in Group A and the majority of the patients
      with abnormal halitometry presented with a tonsillolith at the moment of
      examination. A tonsillolith was present in 75% of the patients with abnormal
      halitometry and only 6% of patients with normal halitometry values. CONCLUSIONS:
      The presence of a tonsillolith represents a tenfold increased risk of abnormal
      VSC halitometry and can be considered as a predictable factor for abnormal
      halitometry in patients with CCT.

PMID- 18037822
TI  - Lip service will no longer be enough.

PMID- 18037823
TI  - Peritonsillar abscess.

PMID- 18037824
TI  - Phossy jaws.

PMID- 18037825
TI  - Tilting at windmills.

PMID- 18037826
TI  - A distinctive entity.

PMID- 18037827
TI  - Labiogingival notch.

PMID- 18037828
TI  - High quality, less bias.

PMID- 18037836
TI  - North West gets new dental school to combat shortage.

PMID- 18037841
TI  - Continuous consent and dignity in dentistry.
AB  - Despite the heavy emphasis on consent in the ethical code of the General Dental
      Council (GDC), it is often overlooked that communication difficulties between
      patient and dentist can cause problems in maintaining genuine consent during
      interventions. Inconsistencies in the GDC's Standards for dental professionals
      and Principles of patient consent guidelines are examined in this article, and it
      is concluded that more emphasis must be placed on continuous consent as an
      ongoing process essential to maintaining patients' dignity in dentistry.

PMID- 18037842
TI  - Unusual wooden foreign body in the palate.
AB  - We report a case of a palatal calcified foreign body simulating an odontogenic
      lesion. Surgical exploration revealed a calcified mass that was analysed under
      light microscopy and identified as a vegetal foreign body. Further scanning
      electron microscopy analysis revealed that the foreign body was a piece of wood.
      Hard palate foreign bodies have been reported previously, however, it seems that
      this is the first case of its kind.

PMID- 18037843
TI  - Interference of electrical dental equipment with implantable cardioverter
      defibrillators.
AB  - OBJECTIVE: To determine whether electromagnetic interference with implantable
      cardioverter-defibrilllators (ICDs) occurs during the use of electrical dental
      equipment. MATERIAL AND METHODS: Ten different electrical dental devices were
      tested for their ability to interfere with the function of three types of ICDs at
      different intervals for 90 seconds, during which the ICD activity was monitored
      by telemetry. RESULTS: Only one ultrasonic bath cleaner interfered with two of
      the ICDs tested up to a distance of 12.5 cm, both during continuous use and
      intermittent operation. In contrast, the dental chair, electrosurgical unit, both
      handpieces, ultrasonic tooth scaler, both amalgamators and two other types of
      ultrasonic bath cleaners failed to produce interference at the minimum distance
      of 2.5 cm. CONCLUSION: Our results suggest that normal clinical use of dental
      electrical equipment does not have significant effects on the ICDs tested.

PMID- 18037844
TI  - A brief guide to clinical guidelines.
AB  - Guidelines in clinical dentistry are regularly growing in number. At their best,
      these represent succinct evidence-based recommendations that are directly
      applicable and improve clinical outcome and cost-effectiveness of interventions.
      At worst these are highly biased (eminence-based) with limited supporting
      evidence and questionable applicability to dental practice. This paper presents
      an overview of available clinical guidelines within dentistry and using examples,
      discusses their evaluation and how practitioners may use these.

PMID- 18037845
TI  - Prilocaine induced methaemoglobinaemia in a medically compromised patient. Was
      this an inevitable consequence of the dose administered?
AB  - Patient M, a 45-year old female, was admitted for extractions with local
      anaesthetic, sedation and monitoring. This was to be carried out on an in patient
      basis due to the patient's extensive medical history which included rheumatic
      heart disease, previous deep vein thrombosis and severe ulcerative colitis.
      Patient M also gave a history of allergy to penicillin and lignocaine. The
      procedure was completed without incident, local anaesthesia having been achieved
      using Citanest with Octapressin (prilocaine 30 mg/ml and felypressin 0.03 unit/ml
      2 ml cartridge). However, on recovery Patient M's oxygen saturations dropped to
      90% on air and although she had no symptoms, the levels could not be improved
      with supplemental oxygen. A diagnosis of methaemoglobinaemia (MetHb) was
      established, a rare complication associated with the administration of
      prilocaine. Patient M was transferred to the high dependency unit and was given
      methylthioninium chloride (methylene blue) intravenously. Her oxygen saturations
      quickly returned to normal and she was discharged the following day. This case
      highlights issues relating to the risk of developing MetHb, what is considered
      the maximum safe dose of prilocaine and some incongruities the authors feel exist
      in the literature.

PMID- 18037852
TI  - Human diseases - the Newcastle experience.
AB  - The second edition of The first five years, published by the General Dental
      Council in 2002, identifies human diseases as a specific subject to be taught as
      part of the BDS curriculum. It states clearly the particular learning outcomes of
      such a course and then identifies a range of subjects (pathology, microbiology,
      medicine, surgery, pharmacology, therapeutics, accident and emergency services
      and medical emergencies) which should constitute the programme. Previously, many
      of these topics were taught and examined separately. In this article, we would
      like to share the Newcastle experience of developing a course in human diseases
      alongside the GDC guidelines.

PMID- 18037853
TI  - Assessment of dental student posture in two seating conditions using RULA
      methodology - a pilot study.
AB  - OBJECTIVES: To assess dental students' posture on two different seats in order to
      determine if one seat predisposes to a difference in working posture. DESIGN: A
      between-subject experimental design was selected. SETTING: The study was
      undertaken at the University of Birmingham School of Dentistry in 2006. Subjects
      (materials) and methods Sixty second year dental students at the University of
      Birmingham who were attending their fi rst classes in the phantom head laboratory
      were randomly selected and allocated to two different seats (30 Bambach Saddle
      Seats and 30 conventional seats). Students were trained in the use of the seats.
      After ten weeks, the students were observed, photographs were taken by the
      researcher and these were assessed using Rapid Upper Limb Assessment (RULA). MAIN
      OUTCOME MEASURES: The posture of the students was assessed using the RULA. Each
      student was given a risk score. A Mann Whitney test was used for statistical
      analysis. RESULTS: The results indicated that the students using the conventional
      seat recorded significantly higher risk scores (p <0.05) when compared with the
      students using Bambach Saddle Seat, suggesting an improvement in posture when
      using the Bambach Saddle Seat. CONCLUSION: RULA has identified that dental
      students using a Bambach Saddle Seat were able to maintain an acceptable working
      posture during simulated dental treatment and this seating may reduce the
      development of work-related musculoskeletal disorders.

PMID- 18037871
TI  - Anthracycline-induced heart failure.

PMID- 18037872
TI  - Tumor dormancy: separating observations from experimental science.

PMID- 18037873
TI  - Active surveillance for favorable-risk prostate cancer: who, how and why?
AB  - Active surveillance for favorable-risk prostate cancer has become increasingly
      common in populations in which screening for prostate cancer is widespread, owing
      to evidence that in many patients screening results in the detection of disease
      that is not clinically significant (i.e. untreated, it would not pose a threat to
      health). The approach is supported by data demonstrating that patients who have
      clinically insignificant disease can be identified with reasonable accuracy, and
      that patients who are initially classified as low risk but reclassified over time
      as higher risk and are treated radically are still cured in most cases. It is
      important to identify patients who have a low probability of disease progression
      during their lifetime according to clinical and pathologic features of the
      disease, patient age and comorbidity. Close monitoring of patients over time and
      availability of reasonable criteria for intervention, which will both identify
      more-aggressive disease in a timely fashion and not result in excessive
      treatment, are crucial. It is also important to communicate appropriately with
      the patient, to reduce the psychological burden of living with untreated cancer.
      The results of active surveillance, the criteria for patient selection and the
      appropriate thresholds for intervention are reviewed in this article.

PMID- 18037874
TI  - Tumor dormancy and surgery-driven interruption of dormancy in breast cancer:
      learning from failures.
AB  - Primary tumor removal, usually considered intrinsically beneficial, can perturb
      metastatic homeostasis, and for some patients results in the acceleration of
      metastatic cancer. The continuous-growth model is required to yield to an
      interrupted-growth model, the implications of which are episodes of tumor
      dormancy. This Review analyzes the recent evolution of two paradigms related to
      the development of breast cancer metastases. The evolution of the paradigms
      described herein is supported by a growing body of findings from experimental
      models, and is required to explain breast cancer recurrence dynamics for patients
      undergoing surgery with or without adjuvant chemotherapy.

PMID- 18037875
TI  - Bisphosphonates and osteomyelitis of the jaw: a pathogenic puzzle.
AB  - The maxillary and mandibular bones undergo high-turnover remodeling to maintain
      mechanical competence. Common dental or periodontal diseases can increase local
      bone turnover. Bisphosphonates (BPs) accumulate almost exclusively in skeletal
      sites that have active bone remodeling. The maxillary and mandibular bones are
      preferential sites for accumulation of BPs, which become buried under new layers
      of bone and remain biologically inactive for a long time. Surgical
      odontostomatological procedures create open bony wounds that heal quickly and
      without infection, as a result of activation of osteoclasts and subsequently
      osteoblasts. Once BPs are removed from the bone via activation of osteoclasts
      after a tooth extraction or a periodontal procedure, they induce osteoclast
      apoptosis. This inhibition of osteoclast bone resorption impairs bone wound
      healing because of decreased production of cytokines derived from the bone
      matrix, and the bone is exposed to the risk of osteomyelitis and necrosis. The
      pathogenic relationship between BPs and osteonecrosis of the jaw is unclear, but
      there is evidence to indicate an association between high-dose BP treatment and
      exposure to dental infections or oral surgical procedures. A better knowledge of
      the interactions between BPs and jaw and maxillary bone biology will improve
      clinical and therapeutic approaches.

PMID- 18037876
TI  - Sustained ventricular tachycardia in a thalidomide-treated patient with primary
      plasma-cell leukemia.
AB  - BACKGROUND: A 68-year-old man diagnosed with primary plasma-cell leukemia was
      given thalidomide maintenance treatment for his disease. He had previously failed
      induction therapy with cyclophosphamide, vincristine, adriamycin, and
      dexamethasone, but achieved complete remission after melphalan therapy. Multiple
      syncopal episodes started to occur during thalidomide treatment, and a Holter
      electrocardiogram showed multiple abnormalities, with an episode of sustained
      ventricular tachycardia. INVESTIGATIONS: Blood tests, peripheral blood smear,
      bone-marrow biopsy and aspirate, Holter electrocardiogram. DIAGNOSIS: Sustained
      ventricular tachycardia possibly owing to thalidomide treatment. MANAGEMENT:
      Thalidomide withdrawal, dexamethasone maintenance therapy, monthly oral courses
      of combined melphalan and prednisone, salvage therapy with bortezomib.

PMID- 18037877
TI  - Extensive tubercular neck lymphadenopathy in a man with early-stage tongue
      cancer.
AB  - BACKGROUND: A 66-year-old Asian man presented with a tongue ulcer and without
      palpable metastases to the neck nodes. A thorough clinical examination of the
      head and neck region did not reveal any other primary lesion. To assess the
      status of the neck, PET-CT imaging was advised. INVESTIGATIONS: Physical
      examination, punch biopsy, PET-CT imaging, blood tests, chest radiograph, fine
      needle aspiration biopsy, tumor biopsy, neck incision, tuberculin test, sputum
      culture and histopathology. DIAGNOSIS: Carcinoma of the tongue of pathologic
      stage T2 N0 M0, with tubercular lymphadenitis and no nodal metastases.
      MANAGEMENT: Surgical excision and multidrug antitubercular therapy.

PMID- 18037878
TI  - Isolation and directed differentiation of neural crest stem cells derived from
      human embryonic stem cells.
AB  - Vertebrate neural crest development depends on pluripotent, migratory precursor
      cells. Although avian and murine neural crest stem (NCS) cells have been
      identified, the isolation of human NCS cells has remained elusive. Here we report
      the derivation of NCS cells from human embryonic stem cells at the neural rosette
      stage. We show that NCS cells plated at clonal density give rise to multiple
      neural crest lineages. The human NCS cells can be propagated in vitro and
      directed toward peripheral nervous system lineages (peripheral neurons, Schwann
      cells) and mesenchymal lineages (smooth muscle, adipogenic, osteogenic and
      chondrogenic cells). Transplantation of human NCS cells into the developing chick
      embryo and adult mouse hosts demonstrates survival, migration and differentiation
      compatible with neural crest identity. The availability of unlimited numbers of
      human NCS cells offers new opportunities for studies of neural crest development
      and for efforts to model and treat neural crest-related disorders.

PMID- 18037879
TI  - Identification and targeting of the ROSA26 locus in human embryonic stem cells.
AB  - The derivation of human embryonic stem (hES) cells has opened new avenues for
      studies on human development and provided a potential source of cells for
      replacement therapy. To reveal the full potential of hES cells, it would be
      advantageous to be able to genetically alter them as is routinely done with mouse
      ES cells through homologous recombination. The mouse Rosa26 locus is particularly
      useful for genetic modification as it can be targeted with high efficiency and is
      expressed in most cell types tested. Here we report the identification of the
      human homolog of the mouse Rosa26 locus. We demonstrate targeting of a red
      fluorescent protein (tdRFP) cDNA to this locus through homologous recombination
      and expression of this targeted reporter in multiple hES cell-derived lineages.
      Through recombinase-mediated cassette exchange, we show replacement of the tdRFP
      cDNA with other cDNAs, providing a cell line in which transgenes can be readily
      introduced into a broadly expressed locus.

PMID- 18037880
TI  - Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at
      bivalent genes in mouse ES cells.
AB  - Changes in phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase
      II (RNAP) are associated with transcription initiation, elongation and
      termination. Sites of active transcription are generally characterized by
      hyperphosphorylated RNAP, particularly at Ser 2 residues, whereas inactive or
      poised genes may lack RNAP or may bind Ser 5-phosphorylated RNAP at promoter
      proximal regions. Recent studies have demonstrated that silent developmental
      regulator genes have an unusual histone modification profile in ES cells, being
      simultaneously marked with Polycomb repressor-mediated histone H3K27 methylation,
      and marks normally associated with gene activity. Contrary to the prevailing
      view, we show here that this important subset of developmental regulator genes,
      termed bivalent genes, assemble RNAP complexes phosphorylated on Ser 5 and are
      transcribed at low levels. We provide evidence that this poised RNAP
      configuration is enforced by Polycomb Repressor Complex (PRC)-mediated
      ubiquitination of H2A, as conditional deletion of Ring1A and Ring1B leads to the
      sequential loss of ubiquitination of H2A, release of poised RNAP, and subsequent
      gene de-repression. These observations provide an insight into the molecular
      mechanisms that allow ES cells to self-renew and yet retain the ability to
      generate multiple lineage outcomes.

PMID- 18037881
TI  - MUC1 oncoprotein activates the IkappaB kinase beta complex and constitutive NF
      kappaB signalling.
AB  - Nuclear factor-kappaB (NF-kappaB) is constitutively activated in diverse human
      malignancies by mechanisms that are not understood. The MUC1 oncoprotein is
      aberrantly overexpressed by most human carcinomas and, similarly to NF-kappaB,
      blocks apoptosis and induces transformation. This study demonstrates that
      overexpression of MUC1 in human carcinoma cells is associated with constitutive
      activation of NF-kappaB p65. We show that MUC1 interacts with the high-molecular
      weight IkappaB kinase (IKK) complex in vivo and that the MUC1 cytoplasmic domain
      binds directly to IKKbeta and IKKgamma. Interaction of MUC1 with both IKKbeta and
      IKKgamma is necessary for IKKbeta activation, resulting in phosphorylation and
      degradation of IkappaBalpha. Studies in non-malignant epithelial cells show that
      MUC1 is recruited to the TNF-R1 complex and interacts with IKKbeta-IKKgamma in
      response to TNFalpha stimulation. TNFalpha-induced recruitment of MUC1 is
      dependent on TRADD and TRAF2, but not the death-domain kinase RIP1. In addition,
      MUC1-mediated activation of IKKbeta is dependent on TAK1 and TAB2. These findings
      indicate that MUC1 is important for physiological activation of IKKbeta and that
      overexpression of MUC1, as found in human cancers, confers sustained induction of
      the IKKbeta-NF-kappaB p65 pathway.

PMID- 18037882
TI  - Fibroblast-led collective invasion of carcinoma cells with differing roles for
      RhoGTPases in leading and following cells.
AB  - Imaging of collectively invading cocultures of carcinoma cells and stromal
      fibroblasts reveals that the leading cell is always a fibroblast and that
      carcinoma cells move within tracks in the extracellular matrix behind the
      fibroblast. The generation of these tracks by fibroblasts is sufficient to enable
      the collective invasion of the squamous cell carcinoma (SCC) cells and requires
      both protease- and force-mediated matrix remodelling. Force-mediated matrix
      remodelling depends on integrins alpha3 and alpha5, and Rho-mediated regulation
      of myosin light chain (MLC) activity in fibroblasts, but these factors are not
      required in carcinoma cells. Instead, carcinoma cells use Cdc42 and MRCK
      (myotonic dystrophy kinase-related CDC42-binding protein kinases) mediated
      regulation of MLC to follow the tracks generated by fibroblasts.

PMID- 18037883
TI  - Development of hemodynamic responses and functional connectivity in rat
      somatosensory cortex.
AB  - Functional magnetic resonance imaging (fMRI) is a valuable method for probing
      postnatal circuit refinement and plasticity. However, its use during early
      development has been hindered by uncertainty as to the nature of neurovascular
      coupling in young individuals. Here we used somatosensory stimulation in rats to
      determine age-related parameters of the blood oxygenation level-dependent (BOLD)
      signal from its apparent inception on postnatal day 13 to adulthood. By comparing
      fMRI measurements with electrophysiological recordings, we determined that the
      regional BOLD response in these animals undergoes a systematic decline in latency
      and growth in amplitude over this period. We found no evidence of negative BOLD
      at any age. Maturation of hemodynamic responses correlated with age-dependent
      increases in susceptibility to inhibition of carbonic anhydrase. With knowledge
      of the infant BOLD response characteristics, we showed that interhemispheric and
      higher-order cortical stimulus responses are enhanced during the first several
      weeks after birth.

PMID- 18037884
TI  - Recognition memory: opposite effects of hippocampal damage on recollection and
      familiarity.
AB  - A major controversy in memory research concerns whether recognition is subdivided
      into distinct cognitive mechanisms of recollection and familiarity that are
      supported by different neural substrates. Here we developed a new associative
      recognition protocol for rats that enabled us to show that recollection is
      reduced, whereas familiarity is increased following hippocampal damage. These
      results provide strong evidence that these processes are qualitatively different
      and that the hippocampus supports recollection and not familiarity.

PMID- 18037885
TI  - Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation,
      segregate with spinocerebellar ataxia type 11.
AB  - The microtubule-associated protein tau (encoded by MAPT) and several tau kinases
      have been implicated in neurodegeneration, but only MAPT has a proven role in
      disease. We identified mutations in the gene encoding tau tubulin kinase 2
      (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue
      showed substantial cerebellar degeneration and tau deposition. These data suggest
      that TTBK2 is important in the tau cascade and in spinocerebellar degeneration.

PMID- 18037886
TI  - Genomic analysis of Bartonella identifies type IV secretion systems as host
      adaptability factors.
AB  - The bacterial genus Bartonella comprises 21 pathogens causing characteristic
      intraerythrocytic infections. Bartonella bacilliformis is a severe pathogen
      representing an ancestral lineage, whereas the other species are benign pathogens
      that evolved by radial speciation. Here, we have used comparative and functional
      genomics to infer pathogenicity genes specific to the radiating lineage, and we
      suggest that these genes may have facilitated adaptation to the host environment.
      We determined the complete genome sequence of Bartonella tribocorum by shotgun
      sequencing and functionally identified 97 pathogenicity genes by signature-tagged
      mutagenesis. Eighty-one pathogenicity genes belong to the core genome (1,097
      genes) of the radiating lineage inferred from genome comparison of B. tribocorum,
      Bartonella henselae and Bartonella quintana. Sixty-six pathogenicity genes are
      present in B. bacilliformis, and one has been lost by deletion. The 14
      pathogenicity genes specific for the radiating lineage encode two laterally
      acquired type IV secretion systems, suggesting that these systems have a role in
      host adaptability.

PMID- 18037887
TI  - Identification of heme as the ligand for the orphan nuclear receptors REV
      ERBalpha and REV-ERBbeta.
AB  - The nuclear receptors REV-ERBalpha (encoded by NR1D1) and REV-ERBbeta (NR1D2)
      have remained orphans owing to the lack of identified physiological ligands. Here
      we show that heme is a physiological ligand of both receptors. Heme associates
      with the ligand-binding domains of the REV-ERB receptors with a 1:1 stoichiometry
      and enhances the thermal stability of the proteins. Results from experiments of
      heme depletion in mammalian cells indicate that heme binding to REV-ERB causes
      the recruitment of the co-repressor NCoR, leading to repression of target genes
      including BMAL1 (official symbol ARNTL), an essential component of the circadian
      oscillator. Heme extends the known types of ligands used by the human nuclear
      receptor family beyond the endocrine hormones and dietary lipids described so
      far. Our results further indicate that heme regulation of REV-ERBs may link the
      control of metabolism and the mammalian clock.

PMID- 18037888
TI  - Straightening and sequential buckling of the pore-lining helices define the
      gating cycle of MscS.
AB  - We describe a mechanism connecting the adaptive behavior of the bacterial
      mechanosensitive channel MscS to the flexibility of the pore-lining helix TM3.
      Simulated expansion of the channel structure revealed straightening of a
      characteristic kink near Gly113 in the open state; return to the closed state
      produced an alternative kink at Gly121. Patch-clamp experiments showed that
      higher helical propensity introduced by a G113A mutation prevented inactivation.
      A similar mutation, G121A, kinetically impeded both closure and inactivation.
      Duplicating the glycines at each of these sites to increase flexibility produced
      directly opposite effects. The severely toxic G113A G121A mutation resulted in
      channels that could not inactivate or close with the release of tension. These
      data suggest that the open MscS features straight TM3 helices, which act as
      collapsible 'struts'. Closure and desensitization rely on buckling at Gly121,
      whereas the crystal-like kink at Gly113 is a feature of the inactivated state.

PMID- 18037889
TI  - Follicular shuttling of marginal zone B cells facilitates antigen transport.
AB  - The splenic marginal zone is a site of blood flow, and the specialized B cell
      population that inhabits this compartment has been linked to the capture and
      follicular delivery of blood-borne antigens. However, the mechanism of this
      antigen transport has remained unknown. Here we show that marginal zone B cells
      were not confined to the marginal zone but continuously shuttled between the
      marginal zone and follicular areas, such that many of the cells visited a
      follicle every few hours. Migration to the follicle required the chemokine
      receptor CXCR5, whereas return to the marginal zone was promoted by the
      sphingosine 1-phosphate receptors S1P1 and S1P3. Treatment with an S1P1
      antagonist caused displacement of marginal zone B cells from the marginal zone.
      Marginal zone-follicle shuttling of marginal zone B cells provides an efficient
      mechanism for systemic antigen capture and delivery to follicular dendritic
      cells.

PMID- 18037891
TI  - Gene synthesis by circular assembly amplification.
AB  - Here we report the development of a gene-synthesis technology, circular assembly
      amplification. In this approach, we first constructed exonuclease-resistant
      circular DNA via simultaneous ligation of oligonucleotides. Exonuclease- and
      subsequent mismatch cleaving endonuclease-mediated degradation of the resulting
      ligation mixture eliminated error-rich products, thereby substantially improving
      gene-synthesis quality. We used this method to construct genes encoding a small
      thermostable DNA polymerase, a highly repetitive DNA sequence and large (>4 kb)
      constructs.

PMID- 18037890
TI  - The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the
      entry of peripheral tissue T lymphocytes into afferent lymphatics.
AB  - Although much is known about the migration of T cells from blood to lymph nodes,
      less is known about the mechanisms regulating the migration of T cells from
      tissues into lymph nodes through afferent lymphatics. Here we investigated T cell
      egress from nonlymphoid tissues into afferent lymph in vivo and developed an
      experimental model to recapitulate this process in vitro. Agonism of sphingosine
      1-phosphate receptor 1 inhibited the entry of tissue T cells into afferent
      lymphatics in homeostatic and inflammatory conditions and caused the arrest,
      mediated at least partially by interactions of the integrin LFA-1 with its ligand
      ICAM-1 and of the integrin VLA-4 with its ligand VCAM-1, of polarized T cells at
      the basal surface of lymphatic but not blood vessel endothelium. Thus, the
      increased sphingosine 1-phosphate present in inflamed peripheral tissues may
      induce T cell retention and suppress T cell egress.

PMID- 18037892
TI  - Reversible tuning of a block-copolymer nanostructure via electric fields.
AB  - Block copolymers consisting of incompatible components self-assemble into
      microphase-separated domains yielding highly regular structures with
      characteristic length scales of the order of several tens of nanometres.
      Therefore, in the past decades, block copolymers have gained considerable
      potential for nanotechnological applications, such as in nanostructured networks
      and membranes, nanoparticle templates and high-density data storage media.
      However, the characteristic size of the resulting structures is usually
      determined by molecular parameters of the constituent polymer molecules and
      cannot easily be adjusted on demand. Here, we show that electric d.c. fields can
      be used to tune the characteristic spacing of a block-copolymer nanostructure
      with high accuracy by as much as 6% in a fully reversible way on a timescale in
      the range of several milliseconds. We discuss the influence of various physical
      parameters on the tuning process and study the time response of the nanostructure
      to the applied field. A tentative explanation of the observed effect is given on
      the basis of anisotropic polarizabilities and permanent dipole moments of the
      monomeric constituents. This electric-field-induced effect further enhances the
      high technological potential of block-copolymer-based soft-lithography
      applications.

PMID- 18037893
TI  - Spatially resolved electronic and vibronic properties of single diamondoid
      molecules.
AB  - Diamondoids are a unique form of carbon nanostructure best described as hydrogen
      terminated diamond molecules. Their diamond-cage structures and tetrahedral sp3
      hybrid bonding create new possibilities for tuning electronic bandgaps, optical
      properties, thermal transport and mechanical strength at the nanoscale. The
      recently discovered higher diamondoids have thus generated much excitement in
      regards to their potential versatility as nanoscale devices. Despite this
      excitement, however, very little is known about the properties of isolated
      diamondoids on metal surfaces, a very relevant system for molecular electronics.
      For example, it is unclear how the microscopic characteristics of molecular
      orbitals and local electron-vibrational coupling affect electron conduction,
      emission and energy transfer in the diamondoids. Here, we report the first single
      molecule study of tetramantane diamondoids on Au(111) using scanning tunnelling
      microscopy and spectroscopy. We find that the diamondoid electronic structure and
      electron-vibrational coupling exhibit unique and unexpected spatial correlations
      characterized by pronounced nodal structure across the molecular surfaces. Ab
      initio pseudopotential density functional calculations reveal that much of the
      observed electronic and vibronic properties of diamondoids are determined by
      surface hydrogen terminations, a feature having important implications for
      designing future diamondoid-based molecular devices.

PMID- 18037894
TI  - Electronic structure of single DNA molecules resolved by transverse scanning
      tunnelling spectroscopy.
AB  - Attempts to resolve the energy-level structure of single DNA molecules by
      scanning tunnelling spectroscopy span over the past two decades, owing to the
      unique ability of this technique to probe the local density of states of objects
      deposited on a surface. Nevertheless, success was hindered by extreme technical
      difficulties in stable deposition and reproducibility. Here, by using scanning
      tunnelling spectroscopy at cryogenic temperature, we disclose the energy spectrum
      of poly(G)-poly(C) DNA molecules deposited on gold. The tunnelling current
      voltage (I-V) characteristics and their derivative (dI/dV-V) curves at 78 K
      exhibit a clear gap and a peak structure around the gap. Limited fluctuations in
      the I-V curves are observed and statistically characterized. By means of ab
      initio density functional theory calculations, the character of the observed
      peaks is generally assigned to groups of orbitals originating from the different
      molecular components, namely the nucleobases, the backbone and the counterions.

PMID- 18037895
TI  - The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for
      degradation.
AB  - Metastasis is the primary cause of mortality from cancer, but the mechanisms
      leading to metastasis are poorly understood. In particular, relatively little is
      known about metastasis in cancers of mesenchymal origins, which are known as
      sarcomas. Approximately ten proteins have been characterized as 'metastasis
      suppressors', but how these proteins function and are regulated is, in general,
      not well understood. Gp78 (also known as AMFR or RNF45) is a RING finger E3
      ubiquitin ligase that is integral to the endoplasmic reticulum (ER) and involved
      in ER-associated degradation (ERAD) of diverse substrates. Here we report that
      expression of gp78 has a causal role in the metastasis of an aggressive human
      sarcoma and that this prometastatic activity requires the E3 activity of gp78.
      Further, gp78 associates with and targets the transmembrane metastasis
      suppressor, KAI1 (also known as CD82), for degradation. Suppression of gp78
      increases KAI1 abundance and reduces the metastatic potential of tumor cells, an
      effect that is largely blocked by concomitant suppression of KAI1. An inverse
      relationship between these proteins was confirmed in a human sarcoma tissue
      microarray. Whereas most previous efforts have focused on genetic mechanisms for
      the loss of metastasis suppressor genes, our results provide new evidence for
      post-translational downregulation of a metastasis suppressor by its ubiquitin
      ligase, resulting in abrogation of its metastasis-suppressing effects.

PMID- 18037896
TI  - Pim-1 regulates cardiomyocyte survival downstream of Akt.
AB  - The serine-threonine kinases Pim-1 and Akt regulate cellular proliferation and
      survival. Although Akt is known to be a crucial signaling protein in the
      myocardium, the role of Pim-1 has been overlooked. Pim-1 expression in the
      myocardium of mice decreased during postnatal development, re-emerged after acute
      pathological injury in mice and was increased in failing hearts of both mice and
      humans. Cardioprotective stimuli associated with Akt activation induced Pim-1
      expression, but compensatory increases in Akt abundance and phosphorylation after
      pathological injury by infarction or pressure overload did not protect the
      myocardium in Pim-1-deficient mice. Transgenic expression of Pim-1 in the
      myocardium protected mice from infarction injury, and Pim-1 expression inhibited
      cardiomyocyte apoptosis with concomitant increases in Bcl-2 and Bcl-X(L) protein
      levels, as well as in Bad phosphorylation levels. Relative to nontransgenic
      controls, calcium dynamics were significantly enhanced in Pim-1-overexpressing
      transgenic hearts, associated with increased expression of SERCA2a, and were
      depressed in Pim-1-deficient hearts. Collectively, these data suggest that Pim-1
      is a crucial facet of cardioprotection downstream of Akt.

PMID- 18037897
TI  - CD1 antigen presentation: how it works.
AB  - The classic concept of self-non-self discrimination by the immune system focused
      on the recognition of fragments from proteins presented by classical MHC
      molecules. However, the discovery of MHC-class-I-like CD1 antigen-presentation
      molecules now explains how the immune system also recognizes the abundant and
      diverse universe of lipid-containing antigens. The CD1 molecules bind and present
      amphipathic lipid antigens for recognition by T-cell receptors. Here, we outline
      the recent advances in our understanding of how the processes of CD1 assembly,
      trafficking, lipid-antigen binding and T-cell activation are achieved and the new
      insights into how lipid antigens differentially elicit CD1-restricted innate and
      adaptive T-cell responses.

PMID- 18037898
TI  - Engulfment of apoptotic cells: signals for a good meal.
AB  - The clearance of apoptotic cells by phagocytes is an integral component of normal
      life, and defects in this process can have significant implications for self
      tolerance and autoimmunity. Recent studies have provided new insights into the
      engulfment process, including how phagocytes seek apoptotic cells, how they
      recognize and ingest these targets and how they maintain cellular homeostasis
      after the 'meal'. Several new factors that regulate engulfment have been
      identified, whereas the roles of some of the older players require revision. This
      Review focuses on these recent developments and attempts to highlight some of the
      important questions in this field.

PMID- 18037900
TI  - Predicting protein function from sequence and structure.
AB  - While the number of sequenced genomes continues to grow, experimentally verified
      functional annotation of whole genomes remains patchy. Structural genomics
      projects are yielding many protein structures that have unknown function.
      Nevertheless, subsequent experimental investigation is costly and time-consuming,
      which makes computational methods for predicting protein function very
      attractive. There is an increasing number of noteworthy methods for predicting
      protein function from sequence and structural data alone, many of which are
      readily available to cell biologists who are aware of the strengths and pitfalls
      of each available technique.

PMID- 18037899
TI  - Multivalent engagement of chromatin modifications by linked binding modules.
AB  - Various chemical modifications on histones and regions of associated DNA play
      crucial roles in genome management by binding specific factors that, in turn,
      serve to alter the structural properties of chromatin. These so-called effector
      proteins have typically been studied with the biochemist's paring knife--the
      capacity to recognize specific chromatin modifications has been mapped to an
      increasing number of domains that frequently appear in the nuclear subset of the
      proteome, often present in large, multisubunit complexes that bristle with
      modification-dependent binding potential. We propose that multivalent
      interactions on a single histone tail and beyond may have a significant, if not
      dominant, role in chromatin transactions.

PMID- 18037901
TI  - An extended epidermal response heals cutaneous wounds in the absence of a hair
      follicle stem cell contribution.
AB  - Hair follicles have been observed to provide a major cellular contribution to
      epidermal healing, with emigration of stem-derived cells from the follicles
      aiding in wound reepithelialization. However, the functional requirements for
      this hair follicle input are unknown. Here we have characterized the keratinocyte
      stem cell status of mutant mice that lack all hair follicle development on their
      tail, and analyzed the consequent alterations in epidermal wound healing rate and
      mechanisms. In analyzing stem cell behavior in embryonic skin we found that
      clonogenic keratinocytes are relatively frequent in the ectoderm prior to hair
      follicle formation. However, their frequency in the interfollicular epidermis
      drops sharply by birth, at which time the majority of stem cells are present
      within the hair follicles. We find that in the absence of hair follicles
      cutaneous wounds heal with an acute delay in reepithelialization. This delay is
      followed by expansion of the region of activated epidermis, beyond that seen in
      normal haired skin, followed by appropriate wound closure. JID Journal Club
      article: for questions, answers, and open discussion about this article please go
      to http://network.nature.com/group/jidclub.

PMID- 18037902
TI  - Downregulation of melanin synthesis by haginin A and its application to in vivo
      lightening model.
AB  - Haginin A, an isoflav-3-ens isolated from the branch of Lespedeza cyrtobotrya, is
      almost unknown. Here, we report that haginin A exhibits a strong hypopigmentary
      effect in Melan-a cells and significantly inhibits melanin synthesis. Haginin A
      shows potent inhibitory effects with an IC(50) (half-maximal inhibitory
      concentration) value of 5.0 microM on mushroom tyrosinase activity, and
      functioned as a noncompetitive inhibitor. Also, haginin A decreased
      microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase
      related protein-1 (TRP-1) protein production. To identify the signaling pathway
      of haginin A, the ability of haginin A to influence extracellular signal
      regulated protein kinase (ERK) and Akt/protein kinase B (PKB) activation was
      investigated. Apparently, haginin A induced ERK and Akt/PKB in a dose-dependent
      manner. In addition, the specific inhibition of the ERK and the Akt/PKB signaling
      pathways by PD98059 and LY294002, respectively, increased melanin synthesis.
      Furthermore, haginin A decreased UV-induced skin pigmentation in brown guinea
      pigs. Also, haginin A presented remarkable inhibition on the body pigmentation in
      the zebrafish model system and decreased tyrosinase activity. Together, haginin A
      is an effective inhibitor of hyperpigmentation caused by UV irradiation or by
      pigmented skin disorders through downregulation via ERK and Akt/PKB activation,
      MITF, and also by the subsequent downregulation of tyrosinase and TRP-1
      production.

PMID- 18037903
TI  - Redistribution of LRIG proteins in psoriasis.
AB  - The human leucine-rich repeats and immunoglobulin-like domains (LRIG) family is
      composed of three members, LRIG1, -2, and -3, which are all expressed in human
      skin. LRIG1 negatively regulates growth factor signaling and is involved in the
      regulation of epidermal stem cell quiescence. Ablation of Lrig1 in mice results
      in psoriasiform epidermal hyperplasia. Hence, the LRIG proteins may be important
      for epidermal homeostasis and in psoriasis. Therefore, we analyzed the LRIG mRNA
      levels and the cellular and subcellular distribution of LRIG proteins in normal
      and psoriatic skin. The mRNA levels of LRIG1, -2, and -3 were not significantly
      different in psoriatic epidermis compared to clinically normal epidermis from the
      same patient. Immunohistochemistry showed that all three LRIG proteins were
      expressed in unique and specific patterns both in normal and psoriatic skin.
      Intriguingly, in psoriatic epidermis, the LRIG protein expression patterns were
      altered compared to normal skin. These results indicate that the LRIG proteins
      may have a role in epidermal homeostasis and psoriasis.

PMID- 18037904
TI  - HDAC activity is required for p65/RelA-dependent repression of PPARdelta-mediated
      transactivation in human keratinocytes.
AB  - Peroxisome proliferator-activated receptors (PPARs) play a key role in
      differentiation, inflammation, migration, and survival of epidermal
      keratinocytes. The NF-kappaB has long been known to play pivotal roles in immune
      and inflammatory responses, and furthermore NF-kappaB has been implicated in the
      regulation of epidermal homeostasis. Recent studies have established that
      p65/RelA is a potent repressor of PPARdelta-mediated transactivation in human
      keratinocytes. In this article we further investigate the molecular mechanisms
      dictating the NF-kappaB-dependent repression of PPARdelta in human keratinocytes.
      We demonstrate that repression is unique to p65/RelA, as no other member of the
      NF-kappaB family had an impact on PPARdelta-mediated transactivation.
      Interestingly, our results show that p65/RelA only represses PPARdelta-dependent
      transactivation when PPARdelta is bound to DNA via its DNA-binding domain. We
      show that repression is sensitive to inhibition of histone deacetylases (HDACs)
      by tricostatin A (TSA), suggesting that HDAC activity is indispensable for
      p65/RelA-mediated repression. Accordingly, we demonstrate that a ternary complex
      consisting of PPARdelta, p65/RelA, and HDAC1 is formed in vivo. Finally, we
      demonstrate that TSA relieves tumor necrosis factor-alpha (TNFalpha)-induced
      repression of PPARdelta-mediated transactivation of the PPARdelta target gene
      adipose differentiation-related protein (ADRP) indicating that cross-talk between
      PPARdelta and NF-kappaB is of biological significance in human keratinocytes.

PMID- 18037905
TI  - Effects of KP-496, a novel dual antagonist at the cysteinyl leukotriene receptor
      1 and the thromboxane A(2) receptor, on airway obstruction in guinea pigs.
AB  - BACKGROUND AND PURPOSE: KP-496 is a novel dual antagonist for cysteinyl
      leukotriene receptor 1 (CysLT(1)) and thromboxane A(2) (TXA(2)) receptor (TP).
      The aim of this study was to evaluate the pharmacological profile of inhaled KP
      496 and its effects on airway obstruction. EXPERIMENTAL APPROACH: Antagonist
      activities of inhaled KP-496 were investigated using bronchoconstriction induced
      in guinea pigs by LTD(4) or U46619, a stable TXA(2) mimetic. Guinea pigs
      sensitized with injections of ovalbumin were used to assess the effects of
      inhaled KP-496 on bronchoconstriction induced by antigen (i.v.). Another set of
      guinea pigs were sensitized and challenged with ovalbumin by inhalation and the
      effects of inhaled KP-496 on immediate and late airway responses and airway
      hyperresponsiveness were investigated. KEY RESULTS: KP-496 significantly
      inhibited LTD(4)- and U46619-induced bronchoconstriction in a dose-dependent
      manner. The inhibitory effects of KP-496 (1%) were comparable to those of
      montelukast (a CysLT(1) antagonist, p.o., 0.3 mg kg(-1)) or seratrodast (a TP
      antagonist, p.o., 3 mg kg(-1)). KP-496 (1%) and oral co-administration of
      montelukast (10 mg kg(-1)) and seratrodast (20 mg kg(-1)) significantly inhibited
      antigen-induced bronchoconstriction, whereas administration of montelukast or
      seratrodast separately did not inhibit antigen-induced bronchoconstriction. KP
      496 exhibited dose-dependent and significant inhibitory effects on the immediate
      and late airway responses and airway hyperresponsiveness following antigen
      challenge. CONCLUSIONS AND IMPLICATIONS: KP-496 exerts effects in guinea pigs
      which could be beneficial in asthma. These effects of KP-496 were greater than
      those of a CysLT(1) antagonist or a TP antagonist, in preventing antigen-induced
      airway obstruction.

PMID- 18037906
TI  - Comparison of the induction profile for drug disposition proteins by typical
      nuclear receptor activators in human hepatic and intestinal cells.
AB  - BACKGROUND AND PURPOSE: Certain nuclear receptors (NRs) such as the constitutive
      androstane receptor (CAR), pregnane X receptor (PXR) and farnesoid X receptor
      (FXR) mediate induction of some cytochrome P450 enzymes and ABC transporters but
      conflicting reports exist. The purpose of this study was to assess the reasons
      for these discrepancies and use a standardized approach to compare activators of
      NRs. EXPERIMENTAL APPROACH: Dexamethasone, pregnenolone 16alpha-carbonitrile,
      rifampicin, phenobarbital and chenodeoxycholic acid were incubated with HepG2,
      Caco-2 and cryopreserved human hepatocytes prior to analysis of mRNA and protein
      for CYP2B6, CYP3A4, CYP3A5, ABCB1, ABCC1, ABCC2, PXR, CAR and FXR. KEY RESULTS:
      Dexamethasone significantly up-regulated PXR, CYP3A4 and ABCB1 expression in
      HepG2 and Caco-2 cells. As a result, including dexamethasone as a media
      supplement masked the induction of these genes by pregnenolone 16alpha
      carbonitrile, which may explain discrepancies between previous reports. In the
      absence of dexamethasone, significant activator-dependent induction was observed
      in all cell types. Significant correlations were observed between the fold
      increase in mRNA and in protein, which were, for most instances, logarithmic.
      Changes in mRNA expression were greater in cell lines than primary cells but for
      most transcripts correlations were observed between fold increases in HepG2 and
      hepatocytes. CONCLUSIONS AND IMPLICATIONS: Clearly, no in vitro system can
      imitate the physiology of a hepatocyte or intestinal cell within an intact organ
      in vivo, but these data explain some of the discrepancies reported between
      laboratories and have important implications for study design.

PMID- 18037907
TI  - Role of cGMP-dependent protein kinase in development of tolerance to
      nitroglycerine in porcine coronary arteries.
AB  - BACKGROUND AND PURPOSE: The cGMP-dependent protein kinase (PKG) is a key enzyme
      for nitrovasodilator-induced vasodilation. The present study was to determine its
      role in nitrate tolerance. EXPERIMENTAL APPROACH: isolated porcine coronary
      arteries were incubated for 24 h with nitroglycerin (NTG) and their relaxant
      responses were determined. PKG activity was assayed by measuring the
      incorporation of (32)P into BPDEtide. PKG protein was determined by Western
      blotting and PKG mRNA by real-time PCR. KEY RESULTS: A 24 h incubation with NTG
      attenuated relaxation of coronary arteries to NTG, which was associated with
      decreased PKG activity. The nitrate tolerance induced with NTG at 10(-7) M was
      affected by a scavenger of reactive oxygen species and the tolerance induced with
      NTG at 10(-6) and 10(-5) M showed cross-tolerance to DETA NONOate and 8-Br-cGMP
      (a cell permeable cGMP analogue). PKG protein and mRNA were down-regulated by a
      24 h incubation with NTG at 10(-5) M but not at 10(-7) M. Acute exposure to
      exogenous superoxide inhibited PKG activity stimulated by NTG at 10(-7) M but not
      at 10(-5) M. Superoxide had no effect on PKG activity stimulated with exogenous
      cGMP. CONCLUSIONS AND IMPLICATIONS: Nitrate tolerance induced by NTG at low
      concentrations may result from an increased production of reactive oxygen species
      acting on sites upstream of PKG. The tolerance induced by NTG at higher
      concentrations may be in part due to suppression of PKG expression resulting from
      sustained activation of the enzyme. These distinct mechanisms of nitrate
      tolerance may be of clinical significance.

PMID- 18037908
TI  - Cardiac capsaicin-sensitive sensory nerves regulate myocardial relaxation via S
      nitrosylation of SERCA: role of peroxynitrite.
AB  - BACKGROUND AND PURPOSE: Sensory neuropathy develops in the presence of
      cardiovascular risk factors (e.g. diabetes, dyslipidemia), but its pathological
      consequences in the heart are unclear. We have previously shown that systemic
      sensory chemodenervation by capsaicin leads to impaired myocardial relaxation and
      diminished cardiac nitric oxide (NO) content. Here we examined the mechanism of
      diminished NO formation and if it may lead to a reduction of peroxynitrite (ONOO(
      ))-induced S-nitrosylation of sarcoendoplasmic reticulum Ca(2+)-ATPase (SERCA2a).
      EXPERIMENTAL APPROACH: Male Wistar rats were treated with capsaicin for 3 days to
      induce sensory chemodenervation. Seven days later, myocardial function and
      biochemical parameters were measured. KEY RESULTS: Capsaicin pretreatment
      significantly increased left ventricular end-diastolic pressure (LVEDP) decreased
      cardiac NO level, Ca(2+)-dependent NO synthase (NOS) activity, and NOS-3 mRNA.
      Myocardial superoxide content, xanthine oxidoreductase and NADPH oxidase
      activities did not change, although superoxide dismutase (SOD) activity
      increased. Myocardial and serum ONOO(-) concentration and S-nitrosylation of
      SERCA2a were significantly decreased. CONCLUSIONS AND IMPLICATIONS: Our results
      show that sensory chemodenervation decreases cardiac NO via decreased expression
      and activity of Ca(2+)-dependent NOS and increases SOD activity, thereby leading
      to decreased basal ONOO(-) formation and reduction of S-nitrosylation of SERCA2a,
      which causes impaired myocardial relaxation characterized by increased left
      ventricular end-diastolic pressure (LVEDP). This suggests that capsaicin
      sensitive sensory neurons regulate myocardial relaxation via maintaining basal
      ONOO(-) formation and SERCA S-nitrosylation.

PMID- 18037909
TI  - Mechanisms of potentiation of the mammalian GABAA receptor by the marine
      cembranoid eupalmerin acetate.
AB  - BACKGROUND AND PURPOSE: Eupalmerin acetate (EPA) is a marine diterpene compound
      isolated from the gorgonian octocorals Eunicea succinea and Eunicea mammosa. The
      compound has been previously shown to modulate muscle-type and neuronal nicotinic
      acetylcholine receptors, which are inhibited in the presence of low micromolar
      concentrations of EPA. In this study, we examined the effect of EPA on another
      transmitter-gated ion channel, the GABA(A) receptor. EXPERIMENTAL APPROACH: Whole
      cell and single-channel recordings were made from HEK 293 cells transiently
      expressing rat wild-type and mutant alpha1beta2gamma2L GABA(A) receptors. KEY
      RESULTS: Our findings demonstrate that, at micromolar concentrations, EPA
      potentiates the rat alpha1beta2gamma2L GABA(A) receptor. The analysis of single
      channel currents recorded in the presence of EPA showed that the kinetic mode of
      action of EPA is similar to that of neuroactive steroids. Mutations to residues
      alpha1Q241 and alpha1N407/Y410, previously shown to affect receptor modulation by
      neurosteroids, also diminished potentiation by EPA. Exposure to a steroid
      antagonist, (3alpha,5alpha)-17-phenylandrost-16-en-3-ol, reduced potentiation by
      EPA. Additionally, exposure to EPA led to potentiation of GABA(A) receptors
      activated by very high concentrations (1-10 microM) of allopregnanolone. In
      tadpole behavioural assays, EPA caused loss of righting reflex and loss of
      swimming reflex. CONCLUSIONS AND IMPLICATIONS: We conclude that EPA either
      interacts with the putative neurosteroid binding site on the GABA(A) receptor or
      shares with neurosteroids the key transduction elements involved in channel
      potentiation by steroids. The results indicate that cembranoids represent a novel
      class of GABA(A) receptor modulators.

PMID- 18037910
TI  - Cloning and pharmacological characterization of the guinea pig P2X7 receptor
      orthologue.
AB  - BACKGROUND AND PURPOSE: The human, rat, and mouse P2X(7) receptors have been
      previously characterized, and in this study we report the cloning and
      pharmacological properties of the guinea pig orthologue. EXPERIMENTAL APPROACH: A
      cDNA encoding for the guinea pig P2X(7) receptor was isolated from a guinea pig
      brain library. The receptor was expressed in U-2 OS cells using the BacMam viral
      expression system. A monoclonal antibody was used to confirm high levels of cell
      surface expression and the functional properties were determined in ethidium
      bromide accumulation studies. KEY RESULTS: The predicted guinea pig protein is
      one amino acid shorter than the human and rat orthologues and over 70% identical
      to the rat and human receptors. In contrast to human and rat P2X(7) receptors, 2'
      &3'-O-(4benzoylbenzoyl)ATP (BzATP) was a partial agonist of the guinea pig P2X(7)
      receptor when compared to ATP and acted as an antagonist in some assays. However,
      as at other species orthologues, BzATP was more potent than ATP. The guinea pig
      P2X(7) receptor possessed higher affinity for 1-[N,O-bis(5-isoquinoline
      sulphonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN62), suramin and Coomassie
      Brilliant Blue than human or rat P2X(7) receptors suggesting that it is
      pharmacologically different to other rodent or human P2X(7) receptors.
      CONCLUSIONS AND IMPLICATIONS: The guinea pig recombinant P2X(7) receptor displays
      a number of unique properties that differentiate it from the human, rat and mouse
      orthologues and this structural and functional information should aid in our
      understanding of the interaction of agonists and antagonist with the P2X(7)
      receptor.

PMID- 18037911
TI  - Differential effects of glucose on agonist-induced relaxations in human
      mesenteric and subcutaneous arteries.
AB  - BACKGROUND AND PURPOSE: Acute periods of hyperglycaemia are strongly associated
      with vascular disorder, yet the specific effects of high glucose on human blood
      vessel function are not fully understood. In this study we (1) characterized the
      endothelial-dependent relaxation of two similarly sized but anatomically distinct
      human arteries to two different agonists and (2) determined how these responses
      are modified by acute exposure to high glucose. EXPERIMENTAL APPROACH: Ring
      segments of human mesenteric and subcutaneous arteries were mounted in a wire
      myograph. Relaxations to acetylcholine and bradykinin were determined in a
      control (5 mM) and high glucose (20 mM) environment over a 2 and 6 h incubation
      period. KEY RESULTS: Bradykinin-induced relaxation in both sets of vessels was
      mediated entirely by EDHF whilst that generated by acetylcholine, though
      principally generated by EDHF, also had contribution from prostacyclin and
      possibly nitric oxide in mesenteric and subcutaneous vessels, respectively. A 2-h
      incubation of high glucose impaired bradykinin-induced relaxation of subcutaneous
      vessels whilst, in contrast, the relaxation generated by bradykinin in mesenteric
      vessels was enhanced at the same time point. High glucose significantly augmented
      the relaxation generated by acetylcholine in mesenteric and subcutaneous vessels
      at a 2 and 6 h incubation point, respectively. CONCLUSIONS AND IMPLICATIONS:
      Short periods of high glucose exert a variable influence on endothelial function
      in human isolated blood vessels that is dependent on factors of time, agonist
      used and vessel studied. This has implications for how we view the effects of
      acute hyperglycaemia found in patients with diabetes mellitus as well as other
      conditions.

PMID- 18037912
TI  - Both alpha1 and alpha2-adrenoceptors mediate the cardiovascular responses to
      noradrenaline microinjected into the bed nucleus of the stria terminal of rats.
AB  - BACKGROUND AND PURPOSE: We have previously shown that noradrenaline microinjected
      into the bed nucleus of stria terminalis (BST) elicited pressor and bradycardiac
      responses in unanaesthetized rats. In the present study, we investigated the
      subtype of adrenoceptors that mediates the cardiovascular response to
      noradrenaline microinjection into the BST. EXPERIMENTAL APPROACH: Cardiovascular
      responses following noradrenaline microinjection into the BST of male Wistar rats
      were studied before and after BST pretreatment with different doses of the
      selective alpha(1)-adrenoceptor antagonist WB4101, the alpha(2)-adrenoceptor
      antagonist RX821002, the combination of WB4101 and RX821002, the non-selective
      beta-adrenoceptor antagonist propranolol, the selective beta(1)-adrenoceptor
      antagonist CGP20712 or the selective beta(2)-adrenoceptor antagonist ICI118,551.
      KEY RESULTS: Noradrenaline microinjected into the BST of unanaesthetized rats
      caused pressor and bradycardiac responses. Pretreatment of the BST with different
      doses of either WB4101 or RX821002 only partially reduced the response to
      noradrenaline. However, the response to noradrenaline was blocked when WB4101 and
      RX821002 were combined. Pretreatment with this combination also shifted the
      resulting dose-effect curve to the left, clearly showing a potentiating effect of
      this antagonist combination. Pretreatment with different doses of either
      propranolol or CGP20712 increased the cardiovascular responses to noradrenaline
      microinjected into the BST. Pretreatment with ICI118,551 did not affect
      cardiovascular responses to noradrenaline. CONCLUSION AND IMPLICATIONS: The
      present results indicate that alpha(1) and alpha(2)-adrenoceptors mediate the
      cardiovascular responses to noradrenaline microinjected into the BST. In
      addition, they point to an inhibitory role played by the activation of local
      beta(1)-adrenoceptors in the cardiovascular response to noradrenaline
      microinjected into the BST.

PMID- 18037913
TI  - Role of alpha1-adrenoceptor subtypes in the effects of methylenedioxy
      methamphetamine (MDMA) on body temperature in the mouse.
AB  - BACKGROUND AND PURPOSE: We have investigated the ability of alpha(1)-adrenoceptor
      antagonists to affect the hyperthermia produced by methylenedioxy methamphetamine
      (MDMA) in conscious mice. EXPERIMENTAL APPROACH: Mice were implanted with
      temperature probes under ether anaesthesia and allowed 2 weeks recovery. MDMA (20
      mg kg(-1)) was administered subcutaneously 30 min after vehicle or test
      antagonist or combination of antagonists and effects on body temperature
      monitored. KEY RESULTS: Following vehicle, MDMA produced a hyperthermia, reaching
      a maximum increase of 1.8 degrees C at 140 min. Prazosin (0.1 mg kg(-1)) revealed
      an early significant hypothermia to MDMA of -1.94 degrees C. The alpha(1A)
      adrenoceptor antagonist RS 100329 (0.1 mg kg(-1)), or the alpha(1D)-adrenoceptor
      antagonist BMY 7378 (0.5 mg kg(-1)) given alone, did not reveal a hypothermia to
      MDMA, but the combination of the two antagonists revealed a significant
      hypothermia to MDMA. The putative alpha(1B)-adrenoceptor antagonist cyclazosin (1
      mg kg(-1)) also revealed a significant hypothermia to MDMA, but actions of
      cyclazosin at the other alpha(1)-adrenoceptor subtypes cannot be excluded.
      CONCLUSIONS AND IMPLICATIONS: More than one subtype of alpha(1)-adrenoceptor is
      involved in a component of the hyperthermic response to MDMA in mouse, probably
      both alpha(1A)- and alpha(1D)-adrenoceptors, and removal of this alpha(1)
      adrenoceptor-mediated component reveals an initial hypothermia.

PMID- 18037914
TI  - Gender-specific vascular effects elicited by chronic ethanol consumption in rats:
      a role for inducible nitric oxide synthase.
AB  - BACKGROUND AND PURPOSE: Epidemiological data suggest that the risk of ethanol
      associated cardiovascular disease is greater in men than in women. This study
      investigates the mechanisms underlying gender-specific vascular effects elicited
      by chronic ethanol consumption in rats. EXPERIMENTAL APPROACH: Vascular
      reactivity experiments using standard muscle bath procedures were performed on
      isolated thoracic aortae from rats. mRNA and protein for inducible NO synthase
      (iNOS) and for endothelial NOS (eNOS) was assessed by RT-PCR or western blotting,
      respectively. KEY RESULTS: In male rats, chronic ethanol consumption enhanced
      phenylephrine-induced contraction in both endothelium-intact and denuded aortic
      rings. However, in female rats, chronic ethanol consumption enhanced
      phenylephrine-induced contraction only in endothelium denuded aortic rings. After
      pre-incubation of endothelium-intact rings with L-NAME, both male and female
      ethanol-treated rats showed larger phenylephrine-induced contractions in aortic
      rings, compared to the control group. Acetylcholine-induced relaxation was not
      affected by ethanol consumption. The effects of ethanol on responses to
      phenylephrine were similar in ovariectomized (OVX) and intact (non-OVX) female
      rats. In the presence of aminoguanidine, but not 7-nitroindazole, the
      contractions to phenylephrine in rings from ethanol-treated female rats were
      greater than that found in control tissues in the presence of the inhibitors.
      mRNA levels for eNOS and iNOS were not altered by ethanol consumption. Ethanol
      intake reduced eNOS protein levels and increased iNOS protein levels in aorta
      from female rats. CONCLUSIONS AND IMPLICATIONS: Gender differences in the
      vascular effects elicited by chronic ethanol consumption were not related to
      ovarian hormones but seemed to involve the upregulation of iNOS.

PMID- 18037915
TI  - Cysteinyl leukotrienes mediate the enhancing effects of indomethacin and aspirin
      on eosinophil production in murine bone marrow cultures.
AB  - BACKGROUND: Prostaglandin E(2) (PGE(2)) suppresses, while indomethacin and
      aspirin enhance, eosinophil production in murine liquid bone-marrow cultures.
      Because cysteinyl leukotrienes (cys-LTs) enhance human eosinophil colony
      formation, we investigated whether the effects of indomethacin and aspirin on
      murine bone-marrow were due to blockade of PGE(2) production alone, or involved
      further promotion of cys-LTs production/signalling. EXPERIMENTAL APPROACH: BALB/c
      liquid bone-marrow cultures were established with IL-5, alone or associated with
      indomethacin, aspirin, or cys-LTs. The effects of preventing cys-LT production or
      signalling were assessed. KEY RESULTS: Indomethacin and aspirin counteracted the
      suppression of eosinophil production by exogenous PGE(2). LTD(4), LTC(4) and
      LTE(4) enhanced IL-5-dependent eosinophil production and further counteracted the
      effect of exogenous PGE(2). The 5-lipoxygenase activating protein (FLAP)
      inhibitor, MK886, a leukotriene synthesis inhibitor, zileuton, the CysLT(1)
      receptor antagonists, MK571 and montelukast, or inactivation of the LTC(4)
      synthase gene, abolished effects of indomethacin and aspirin. MK886 and zileuton
      were ineffective but MK571 and montelukast were effective, against LTD(4).
      Indomethacin, aspirin and LTD(4) failed to enhance eosinophil production in bone
      marrow from CysLT1 receptor-deficient mice. Indomethacin, aspirin and LTD(4) no
      longer counteracted the effects of exogenous PGE(2) in the presence of MK571 and
      montelukast. MK886, MK571 and montelukast had no effect by themselves, or in
      association with PGE(2). CONCLUSIONS AND IMPLICATIONS: Dependence on the FLAP/5
      lipoxygenase/LTC(4) synthase pathway and receptor signalling shows that cyclo
      oxygenase inhibitors act here through endogenous cys-LTs. While PGE(2) does not
      act by suppressing cys-LT production, cys-LTs override PGE(2) signalling.
      Eosinophil production is therefore coordinately regulated by both pathways.

PMID- 18037917
TI  - Curcumin: potential for hepatic fibrosis therapy?
AB  - The beneficial antioxidative, anti-inflammatory and antitumorigenic effects of
      curcumin have been well documented in relation to cancer and other chronic
      diseases. Recent evidence suggests that it may be of therapeutic interest in
      chronic liver disease. Hepatic fibrosis (scarring) occurs in advanced liver
      disease, where normal hepatic tissue is replaced with collagen-rich extracellular
      matrix and, if left untreated, results in cirrhosis. Curcumin inhibits liver
      cirrhosis in a rodent model and exerts multiple biological effects in hepatic
      stellate cells (HSCs), which play a central role in the pathogenesis of hepatic
      fibrosis. In response to liver injury, these cells proliferate producing pro
      inflammatory mediators and extracellular matrix. Curcumin induces apoptosis and
      suppresses proliferation in HSCs. In addition, it inhibits extracellular matrix
      formation by enhancing HSC matrix metalloproteinase expression via PPARgamma and
      suppressing connective tissue growth factor (CTGF) expression. In this issue,
      Chen and co-workers propose that curcumin suppresses CTGF expression in HSC by
      inhibiting ERK and NF-kappaB activation. These studies suggest that curcumin
      modulates several intracellular signalling pathways in HSC and may be of future
      interest in hepatic fibrosis therapy.

PMID- 18037916
TI  - CB2 receptors in the brain: role in central immune function.
AB  - Recently, it has been recognized that the cannabinoid receptor CB2 may play a
      functionally relevant role in the central nervous system (CNS). This role is
      mediated primarily through microglia, a resident population of cells in the CNS
      that is morphologically, phenotypically, and functionally related to macrophages.
      These cells also express the cannabinoid receptor CB1. The CB1 receptor (CB1R) is
      constitutively expressed at low levels while the CB2 receptor (CB2R) is expressed
      at higher levels and is modulated in relation to cell activation state. The
      relatively high levels of the CB2R correspond with microglia being in
      'responsive' and 'primed' states, suggesting the existence of a 'window' of
      functional relevance during which activation of the CB2R modulates microglial
      activities. Signature activities of 'responsive' and 'primed' microglia are
      chemotaxis and antigen processing, respectively. The endocannabinoid 2
      arachidonylglycerol has been reported to stimulate a chemotactic response from
      these cells through the CB2R. In contrast, we have shown in vivo and in vitro
      that the exogenous cannabinoids delta-9-tetrahydrocannabinol and CP55940 inhibit
      the chemotactic response of microglia to Acanthamoeba culbertsoni, an
      opportunistic pathogen that is the causative agent of Granulomatous Amoebic
      Encephalitis, through activation of the CB2R. It is postulated that these
      exogenous cannabinoids superimpose an inhibitory effect on pro-chemotactic
      endocannabinoids that are elicited in response to Acanthamoeba. Furthermore, the
      collective results suggest that the CB2R plays a critical immune functional role
      in the CNS.

PMID- 18037918
TI  - Chlorthalidone inhibits the KvLQT1 potassium current in guinea-pig ventricular
      myocytes and oocytes from Xenopus laevis.
AB  - BACKGROUND AND PURPOSE: Chlorthalidone is used for the treatment of hypertension
      as it produces a lengthening of the cardiac action potential. However, there is
      no experimental evidence that chlorthalidone has electrophysiological effects on
      the potassium currents involved in cardiac repolarization. EXPERIMENTAL APPROACH:
      Ventricular myocytes and oocytes, transfected with human ionic channels that
      produce IK current, were exposed to different concentrations of chlorthalidone.
      Action potentials and potassium currents were recorded using a patch clamp
      technique. To determine which component of the current was affected by
      chlorthalidone, human channel proteins (hERG, minK and KvLQT1) were used. KEY
      RESULTS: Chlorthalidone prolonged the ventricular action potential at 50 and 90%
      by 13 and 14%, respectively. The cardiac potassium currents I(to) and IK(1) were
      not affected by chlorthalidone at any concentration, whereas the delayed
      rectifier potassium current, IK, was blocked in a dose-response, voltage
      independent fashion. In our preparation, 100 microM chlorthalidone blocked the
      two components of the delayed rectifier potassium current with the same potency
      (50.1+/-5% for IK(r) and 54.6+/-6% for IK(s)) (n=7, P<0.05). The chlorthalidone
      sensitive current was slow and saturated at potentials greater than +30 mV. In
      our conditions only the KvLQT1 potassium current was affected by the drug, by
      14%. CONCLUSIONS AND IMPLICATIONS: Chlorthalidone was demonstrated to have a
      direct effect on cardiac ventricular myocytes; it blocked the delayed rectifier
      potassium current (IK), specifically the KvLQT1 component of the potassium
      current. These results indicate that it has potential for use as an
      antiarrhythmic but further studies are needed.

PMID- 18037919
TI  - Regional differences in nitrergic innervation of the smooth muscle of murine
      lower oesophageal sphincter.
AB  - BACKGROUND AND PURPOSE: Anatomical and pharmacological studies have demonstrated
      that the lower oesophageal sphincter (LES) is not a simple homogenous circular
      muscle with uniform innervation. Regional differences have been demonstrated in
      several species including humans. We investigated, for the first time in mice
      LES, regionally distinct physiological and pharmacological characteristics of the
      neuromusculature. EXPERIMENTAL APPROACH: Conventional intracellular recordings
      and pharmacological techniques were employed to evaluate electrical properties
      and functional innervation of smooth muscle cells. Results from CD1 (control),
      nNOS((-/-)) and eNOS((-/-)) genetic knockout mice were compared. KEY RESULTS:
      Smooth muscle of sling and clasp LES displayed unitary membrane potentials of 1-
      4 mV. Transmural nerve stimulation produced a monophasic inhibitory junction
      potential (IJP) in the sling, whereas in the clasp a biphasic IJP, consisting of
      a brief IJP followed by a long-lasting slow IJP (lsIJP), was induced.
      Pharmacological interventions and genetically modified mice were used to
      demonstrate a monophasic apamin-sensitive (purinergic) component in both LES
      regions. However, the nitrergic IJP was monophasic in the sling and biphasic in
      the clasp. Unitary membrane potentials and IJPs were not different in CD1 and
      eNOS((-/-)) mice, suggesting no involvement of myogenic NOS. CONCLUSION AND
      IMPLICATIONS: These data in mouse LES indicate that there are previously
      unreported regional differences in the IJP and that both the apamin-resistant
      monophasic and biphasic IJPs are mediated primarily by nitrergic innervation.

PMID- 18037920
TI  - G-protein-coupled receptor heteromers: function and ligand pharmacology.
AB  - Almost all existing models for G-protein-coupled receptors (GPCRs) are based on
      the occurrence of monomers. Recent studies show that many GPCRs are dimers.
      Therefore for some receptors dimers and not monomers are the main species
      interacting with hormones/neurotransmitters/drugs. There are reasons for
      equivocal interpretations of the data fitting to receptor dimers assuming they
      are monomers. Fitting data using a dimer-based model gives not only the
      equilibrium dissociation constants for high and low affinity binding to receptor
      dimers but also a 'cooperativity index' that reflects the molecular communication
      between monomers within the dimer. The dimer cooperativity index (D(C)) is a
      valuable tool that enables to interpret and quantify, for instance, the effect of
      allosteric regulators. For different receptors heteromerization confers a
      specific functional property for the receptor heteromer that can be considered as
      a 'dimer fingerprint'. The occurrence of heteromers with different
      pharmacological and signalling properties opens a complete new field to search
      for novel drug targets useful to combat a variety of diseases and potentially
      with fewer side effects. Antagonists, which are quite common marketed drugs
      targeting GPCRs, display variable affinities when a given receptor is expressed
      with different heteromeric partners. This fact should be taken into account in
      the development of new drugs.

PMID- 18037921
TI  - Ligand discovery and virtual screening using the program LIDAEUS.
AB  - This paper discusses advances in docking and scoring approaches with examples
      from the high-throughput virtual screening program LIDAEUS. We describe the
      discovery of small molecule inhibitors for the immunophilin CypA, the cyclin
      dependent kinase CDK2 and the cyclapolin series of potent Polo-like kinase
      inhibitors. These results are discussed in the context of advances in massively
      parallel computing and in the development of annotated databases.

PMID- 18037923
TI  - GPR119, a novel G protein-coupled receptor target for the treatment of type 2
      diabetes and obesity.
AB  - GPR119 is a G protein-coupled receptor expressed predominantly in the pancreas
      (beta-cells) and gastrointestinal tract (enteroendocrine cells) in humans. De
      orphanization of GPR119 has revealed two classes of possible endogenous ligands,
      viz., phospholipids and fatty acid amides. Of these, oleoylethanolamide (OEA) is
      one of the most active ligands tested so far. This fatty acid ethanolamide is of
      particular interest because of its known effects of reducing food intake and body
      weight gain when administered to rodents. Agonists at the GPR119 receptor cause
      an increase in intracellular cAMP levels via G(alphas) coupling to adenylate
      cyclase. In vitro studies have indicated a role for GPR119 in the modulation of
      insulin release by pancreatic beta-cells and of GLP-1 secretion by gut
      enteroendocrine cells. The effects of GPR119 agonists in animal models of
      diabetes and obesity are reviewed, and the potential value of such compounds in
      future therapies for these conditions is discussed.

PMID- 18037922
TI  - Pathophysiology of ischaemic stroke: insights from imaging, and implications for
      therapy and drug discovery.
AB  - Preventing death and limiting handicap from ischaemic stroke are major goals that
      can be achieved only if the pathophysiology of infarct expansion is properly
      understood. Primate studies showed that following occlusion of the middle
      cerebral artery (MCA)--the most frequent and prototypical stroke, local tissue
      fate depends on the severity of hypoperfusion and duration of occlusion, with a
      fraction of the MCA territory being initially in a 'penumbral' state.
      Physiological quantitative PET imaging has translated this knowledge in man and
      revealed the presence of considerable pathophysiological heterogeneity from
      patient to patient, largely unpredictable from elapsed time since onset or
      clinical deficit. While these observations underpinned key trials of
      thrombolysis, they also indicate that only patients who are likely to benefit
      should be exposed to its risks. Accordingly, imaging-based diagnosis is rapidly
      becoming an essential component of stroke assessment, replacing the clock by
      individually customized management. Diffusion- and perfusion-weighted MR (DWI
      PWI) and CT-based perfusion imaging are increasingly being used to implement
      this, and are undergoing formal validation against PET. Beyond thrombolysis per
      se, knowledge of the individual pathophysiology also guides management of
      variables like blood pressure, blood glucose and oxygen saturation, which can
      otherwise precipitate the penumbra into the core, and the oligaemic tissue into
      the penumbra. We propose that future therapeutic trials use physiological imaging
      to select the patient category that best matches the drug's presumed mode of
      action, rather than lumping together patients with entirely different
      pathophysiological patterns in so-called 'large trials', which have all failed so
      far.

PMID- 18037924
TI  - Nicotinic acid: an old drug with a promising future.
AB  - Nicotinic acid has been used for decades to treat dyslipidaemic states. In
      particular its ability to raise the plasma HDL cholesterol concentration has led
      to an increased interest in its pharmacological potential. The clinical use of
      nicotinic acid is somewhat limited due to several harmless but unpleasant side
      effects, most notably a cutaneous flushing phenomenon. With the recent discovery
      of a nicotinic acid receptor, it has become possible to better understand the
      mechanisms underlying the metabolic and vascular effects of nicotinic acid. Based
      on these new insights into the action of nicotinic acid, novel strategies are
      currently under development to maximize the pharmacological potential of this
      drug. The generation of both flush-reducing co-medications of nicotinic acid and
      novel drugs targeting the nicotinic acid receptor will provide future therapeutic
      options for the treatment of dyslipidaemic disorders.

PMID- 18037925
TI  - Towards the development of universal, fast and highly accurate docking/scoring
      methods: a long way to go.
AB  - Accelerating the drug discovery process requires predictive computational
      protocols capable of reducing or simplifying the synthetic and/or combinatorial
      challenge. Docking-based virtual screening methods have been developed and
      successfully applied to a number of pharmaceutical targets. In this review, we
      first present the current status of docking and scoring methods, with exhaustive
      lists of these. We next discuss reported comparative studies, outlining criteria
      for their interpretation. In the final section, we describe some of the remaining
      developments that would potentially lead to a universally applicable
      docking/scoring method.

PMID- 18037928
TI  - How can we improve adherence to therapy by patients with rheumatoid arthritis?

PMID- 18037929
TI  - Psoriatic disease--from skin to bone.
AB  - Psoriatic arthritis is an inflammatory joint disease that is heterogeneous in
      presentation and clinical course. Evidence that this disease is distinct from
      rheumatoid arthritis and other spondyloarthropathies is based on data derived
      from characteristic clinical features, histopathologic analyses, immunogenetic
      associations and musculoskeletal imaging. Emphasis has centered previously on a
      dominant role for the T lymphocyte in the inflammatory process; however, studies
      provide support for a major contribution from monocyte-macrophages in the
      initiation and perpetuation of joint and skin inflammation. The occurrence of
      arthritis in the absence of psoriasis in a minority of patients with psoriatic
      arthritis, coupled with divergent genetic risk factors, indicates that psoriatic
      arthritis is distinct from psoriatic skin inflammation. A new terminology,
      psoriatic disease, has emerged that encompasses the various manifestations of
      tissue and organ involvement observed in many psoriasis patients, including
      inflammation in the joint, eye and gut. Moreover, adverse cardiovascular and
      metabolic outcomes in patients with psoriasis or psoriatic arthritis might be
      directly linked to the cutaneous and musculoskeletal manifestations of these
      diseases via subsets of circulating monocytes and tissue macrophages activated by
      inflammatory cytokine networks that arise in the skin and possibly the joint.

PMID- 18037926
TI  - Presynaptic nicotinic receptors: a dynamic and diverse cholinergic filter of
      striatal dopamine neurotransmission.
AB  - The effects of nicotine on dopamine transmission from mesostriatal dopamine
      neurons are central to its reinforcing properties. Only recently however, has the
      influence of presynaptic nicotinic receptors (nAChRs) on dopaminergic axon
      terminals within striatum begun to be understood. Here, rather than simply
      enhancing (or inhibiting) dopamine release, nAChRs perform the role of a
      presynaptic filter, whose influence on dopamine release probability depends on
      presynaptic activity in dopaminergic as well as cholinergic neurons. Both
      mesostriatal dopaminergic neurons and striatal cholinergic interneurons play key
      roles in motivational and sensorimotor processing by the basal ganglia. Moreover,
      it appears that the striatal influence of dopamine and ACh cannot be fully
      appreciated without an understanding of their reciprocal interactions. We will
      review the powerful filtering by nAChRs of striatal dopamine release and discuss
      its dependence on activity in dopaminergic and cholinergic neurons. We will also
      review how nicotine, acting via nAChR desensitization, promotes the sensitivity
      of dopamine synapses to activity. This filtering action might provide a mechanism
      through which nicotine promotes how burst activity in dopamine neurons
      facilitates goal-directed behaviour and reinforcement processing. More generally,
      it indicates that we should not restrict our view of presynaptic nAChRs to simply
      enhancing neurotransmitter release. We will also summarize current understanding
      of the forms and functions of the diverse nAChRs purported to exist on
      dopaminergic axons. A greater understanding of nAChR form and function is
      imperative to guide the design of ligands with subtype-selective efficacy for
      improved therapeutic interventions in nicotine addiction as well as Parkinson's
      disease.

PMID- 18037927
TI  - Beta-arrestins and heterotrimeric G-proteins: collaborators and competitors in
      signal transduction.
AB  - G-protein-coupled receptors (GPCRs), also known as seven transmembrane receptors
      (7-TMRs), are the largest protein receptor superfamily in the body. These
      receptors and their ligands direct a diverse array of physiological responses,
      and hence have broad relevance to numerous diseases. As a result, they have
      generated considerable interest in the pharmaceutical industry as drug targets.
      Recently, GPCRs have been demonstrated to elicit signals through interaction with
      the scaffolding proteins, beta-arrestins-1 and 2, independent of heterotrimeric G
      protein coupling. This review discusses several known G-protein-independent, beta
      arrestin-dependent pathways and their potential physiological and pharmacological
      significance. The emergence of G-protein-independent signalling changes the way
      in which GPCR signalling is evaluated, from a cell biological to a pharmaceutical
      perspective and raises the possibility for the development of pathway specific
      therapeutics.

PMID- 18037930
TI  - Tobacco smoking and autoimmune rheumatic diseases.
AB  - Autoimmune rheumatic diseases are considered to be influenced by both genetic and
      environmental factors. Tobacco smoking has been linked to the development of
      rheumatic diseases, namely systemic lupus erythematosus and rheumatoid arthritis,
      and has been shown to interact with genetic factors to create a significant
      combined risk of disease. Smoking also affects both the course and the outcome of
      rheumatic diseases. Smoking increases the risk of dermatologic features and
      nephritis in systemic lupus erythematosus, rheumatoid nodules and multiple joint
      involvement in rheumatoid arthritis and digital ischemia in systemic sclerosis,
      as well as further increasing the risk of accelerated atherosclerosis in these
      diseases. Smoking is known to modulate the immune system through many mechanisms,
      including the induction of the inflammatory response, immune suppression,
      alteration of cytokine balance, induction of apoptosis, and DNA damage that
      results in the formation of anti-DNA antibodies. No sole mechanism, however, has
      been linked to any of the autoimmune illnesses, which therefore complicates full
      comprehension of the 'smoking effect'. Further studies, perhaps using animal
      models, are needed to analyze the exact effect of smoking on each disease
      separately.

PMID- 18037931
TI  - Adipokines as emerging mediators of immune response and inflammation.
AB  - The scientific interest in the biology of white adipose tissue (WAT) has
      increased since the discovery of leptin in 1994. The description of the product
      of the gene obese (ob) demonstrated the role of adipose tissue in the
      physiopathology of obesity-related diseases, and helped to increase the
      identification of numerous other adipokines, many of a pro-inflammatory nature.
      It has become increasingly evident that WAT-derived adipokines can be considered
      as a hub between obesity-related exogenous factors, such as nutrition and
      lifestyle, and the molecular events that lead to metabolic syndrome, inflammatory
      and/or autoimmune conditions, and rheumatic diseases. In this Review, we will
      discuss the progress in adipokine research, focusing particular attention to the
      roles of leptin, adiponectin, resistin, visfatin, and other recently identified
      adipokines in inflammatory, autoimmune and rheumatic diseases.

PMID- 18037932
TI  - Primer: administrative health databases in observational studies of drug effects-
      advantages and disadvantages.
AB  - Observational studies are important tools for providing information on the safety
      and benefit of approved medications; they provide data on real-life use, rare
      outcomes and long-term effects that were undetectable in randomized controlled
      trials. We review various administrative databases in the US and Canada, in
      addition to European medical records databases, which have been used extensively
      to assess drug safety. We present their advantages, which include their large
      size and the availability of systematic and accurate medication data from
      pharmacies and extensive outcome data from hospital records, and limitations,
      including the questionable validity of diagnostic information and absence of
      information on confounders (e.g. disease severity) and over-the-counter drugs. We
      illustrate these challenges in the investigation of the cardiovascular risks of
      the cyclo-oxygenase 2 inhibitor rofecoxib and highlight important methodological
      issues, beyond the limitations of the databases, which could explain the
      contradictory findings from three observational studies that used these
      databases. We show that issues relating to the duration of drug use, immortal
      time, depletion of susceptibles and overadjustment were problematic sources of
      bias in these studies and discuss remedies to avoid these pitfalls. With careful
      attention to their design and analysis, observational database studies are
      powerful and modern tools for providing crucial data on drug effects.

PMID- 18037933
TI  - Chronic recurrent multifocal osteomyelitis: what is it and how should it be
      treated?
AB  - BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is the most severe
      form of chronic nonbacterial osteomyelitis. In children and adolescents, chronic
      nonbacterial osteomyelitis predominantly affects the metaphyses of the long
      bones, but lesions can occur at any site in the skeleton. Other organs (the skin,
      eyes, gastrointestinal tract and lungs) can also be affected. Clinical diagnosis
      is often difficult because the symptoms and course of disease vary significantly.
      We present a 10-year-old girl diagnosed with CRMO involving several vertebrae,
      the femur and the metatarsus. INVESTIGATIONS: Physical examination, abdominal
      ultra sonography, conventional X-ray, MRI, technetium bone scan,
      esophagogastroduodenoscopy, colonoscopy, tests for HLA-B27 and thiopurine
      methyltransferase, polymerase chain reaction and thoracic vertebral bone
      biopsies. DIAGNOSIS: CRMO and Crohn's disease. MANAGEMENT: The patient's
      condition improved whilst being treated with NSAIDs for 3 months; however, the
      patient had an allergic skin reaction to this therapy. Treatment was switched to
      sulfasalazine, accompanied by 3 weeks of therapy using oral prednisone, but
      sulfasalazine was discontinued 2 months later because the patient exhibited a
      minor elevation in the levels of liver enzymes. The patient was free of
      musculoskeletal symptoms for 6 months, at which time she started to complain
      again about pain in her back and bowel. Multimodal therapy, consisting of
      mesasalazine, corticosteroids (budesonide) and azathioprine, induced clinical
      remission of Crohn's disease.

PMID- 18037934
TI  - Successful therapy of chronic graft-versus-host disease manifesting as pure red
      cell aplasia with single-agent rituximab.

PMID- 18037935
TI  - Clinical-scale single-step CD4(+) and CD8(+) cell depletion for donor innate
      lymphocyte infusion (DILI).
AB  - The ability to selectively deplete or enrich cells of specific phenotype by
      immunomagnetic selection to reduce the risk of GVHD holds significant promise for
      application in adoptive immunotherapy. Current clinical-scale approaches for T
      cell depletion (e.g., CD34(+) selection, CD3(+) depletion), usually deplete
      gammadelta T cells, which may be advantageous in mediating graft-versus-tumor
      (GVT) effects and augmenting the innate immune response against infections. Here,
      we present a new method for depletion of T cells with potential GVHD reactivity
      by using a single-step immunomagnetic protocol, which efficiently depletes CD4(+)
      and CD8(+) alphabeta T cells under good manufacturing practice (GMP) conditions.
      Depletion from unstimulated leukapheresis products (n=6) containing up to 2.0 x
      10(10) cells showed high efficiency (mean log depletion of CD4(+) cells: 4.12,
      CD8(+) cells: 3.77). In addition, immunomagnetic CD4/CD8 depletion resulted in
      passive enrichment of innate lymphocytes (mean recovery of natural killer (NK)
      cells: 38%, gammadelta T cells: 50%). We demonstrated that gammadelta/NK cells
      preserved their proliferative and cytotoxic capacity and conclude that
      simultaneous large-scale depletion of CD4(+)/CD8(+) T cells is feasible and can
      be performed under GMP conditions with high-depletion efficacy for alphabeta T
      cells and recovery of functionally intact innate effector lymphocytes for
      potential use in adoptive immunotherapy studies.

PMID- 18037936
TI  - In vitro and in vivo evaluation of the haematopoietic potential of skeletal
      muscle in a non-human primate model.
AB  - This study was aimed at evaluating the in vitro and in vivo haematopoietic
      potential in macaque skeletal muscle cells. Biopsy samples showed the presence of
      CD34(+) (7.6%), CD90(+) (8.4%), CD117(+), CD31(+), side population (SP) cells (7
      10%) and a low number of CD45(+) cells. In clonogenic and long-term culture
      initiating cell assays, no haematopoietic potential could be detected in either
      total mononuclear cells or SP cells. Regarding in vivo studies, two animals were
      transplanted with unfractionated fresh muscle cells after lethal irradiation.
      Both animals died early after transplant without any evidence of haematopoietic
      reconstitution. In two other monkeys, harvested muscle cells were frozen and
      secondarily marked using a green fluorescent protein (GFP)-lentiviral vector.
      After sublethal irradiation, both animals were transplanted with GFP-expressing
      muscle cells followed by a bone marrow rescue. Both animals had haematopoietic
      reconstitution at days 22 and 25, but no GFP-expressing haematopoietic cells
      could be detected by flow cytometry, either in the blood or in clonogenic cells
      from marrow aspirates. Using PCR assays, GFP(+) cells were detected in a single
      marrow sample of one animal at 41 days after transplantation. These results
      strongly suggest that as opposed to murine muscle, the non-human primate skeletal
      muscle does not harbour cells with a straightforward haematopoietic potential.

PMID- 18037937
TI  - Stem cell-derived cardiomyocytes after bone marrow and heart transplantation.
AB  - Cardiomyocytes are a stable cell population with only limited potential for
      renewal after injury. Tissue regeneration may be due to infiltration of stem
      cells, which differentiate into cardiomyocytes. We have analysed the influx of
      stem cells in the heart of patients who received either a gender-mismatched BMT
      (male donor to female recipient) or a gender-mismatched cardiac transplant (HTX;
      female donor to male recipient). The proportion of infiltrating cells was
      determined by Y-chromosome in situ hybridization combined with
      immunohistochemical cell characterization. In BM transplanted patients and in
      cardiac allotransplant recipients, cardiomyocytes of apparent BM origin were
      detected. The proportions were similar in both groups and amounted up to 1% of
      all cardiomyocytes. The number of stem cell-derived cardiomyocytes did not alter
      significantly in time, but were relatively high in cases where large numbers of
      BM-derived Y-chromosome-positive infiltrating inflammatory cells were present.
      The number of Y-chromosome-positive endothelial cells was small and present only
      in small blood vessels. The number of BM-derived cardiomyocytes in both BMT and
      HTX is not significantly different between the two types of transplantation and
      is at most 1%.

PMID- 18037938
TI  - Comparison of peripheral blood and bone marrow samples for detection of post
      transplant mixed chimerism.

PMID- 18037939
TI  - Chimerism does not predict for outcome after alemtuzumab-based conditioning:
      lineage-specific analysis of chimerism of specific diseases may be more
      informative.

PMID- 18037940
TI  - Pegase 03: a prospective randomized phase III trial of FEC with or without high
      dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first
      line treatment of metastatic breast cancer.
AB  - Pegase 03 is a multicenter prospective randomized phase III trial evaluating the
      impact of first-line high-dose chemotherapy (HDC) with stem cell support on
      overall survival (OS), disease-free survival (DFS) and response rate in 308
      patients with histologically proven metastatic breast cancer responding to
      induction therapy. Eligible patients received four induction cycles with FEC 100
      (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500
      mg/m(2)). Patients with objective response (N=179) were randomized to one cycle
      of HDC (cyclophosphamide 6000 mg/m(2) and thiotepa 800 mg/m(2) (CHUT)) and stem
      cell support (N=88), or no further treatment (N=91). All patients were observed
      until disease progression or death. One toxic death occurred after CHUT. Other
      toxicities were manageable. The response rate at 3 months was higher in the
      intensification arm: 82.7% (25.3% complete response (CR)) versus 59.2% (14.1% CR)
      (P=0.0002). Median follow-up was 48 months. Median DFS was 11 and 6.6 months in
      the intensification and the observation arms, respectively (P=0.0001). There was
      no survival difference: 33.6 versus 27.3% OS at 3 years (P=0.8) and 22.9 versus
      22.3 months median time to relapse in the intensification and observation arms,
      respectively. In this randomized trial, HDC with CHUT improved DFS but not OS,
      corroborating findings from earlier trials.

PMID- 18037941
TI  - Combination of enzyme replacement and hematopoietic stem cell transplantation as
      therapy for Hurler syndrome.
AB  - Hurler syndrome (mucopolysaccharidosis type I, MPS IH) is characterized by a
      deficiency of alpha-L-iduronidase resulting in progressive multiorgan
      dysfunction. We sought to determine whether enzyme replacement therapy (ERT) with
      iduronidase in the peritransplant period affects outcome of hematopoietic stem
      cell transplantation (HSCT) for MPS IH. Seven children with MPS IH at a median
      age of 1.5 years at the time of myeloablative HSCT were eligible. All patients
      had null mutations in IDUA gene. Iduronidase (0.58 mg/kg per dose) was
      administered intravenously in 11-14 weekly doses before HSCT and 8 weekly doses
      after HSCT. The infusions were well tolerated. All patients developed antibodies
      to iduronidase but all engrafted with >90% donor hematopoiesis. A majority of
      patients had significant pulmonary complications before ERT and HSCT but all are
      alive and well with a median follow-up of more than 1 year after HSCT. This
      suggests that ERT prior to HSCT is unlikely to alter engraftment. In addition,
      morbidity was acceptable, despite a previous history of pulmonary difficulties
      that suggested that these patients were high risk for these complications.
      Therefore, we recommend treatment of MPS IH patients with combination of ERT and
      HSCT therapy to further investigate its potential to enhance outcomes with HSCT.

PMID- 18037942
TI  - Preinfusion variables predict the predominant unit in the setting of reduced
      intensity double cord blood transplantation.
AB  - Double cord blood transplantation (DCBT) may overcome the slow hematopoietic
      recovery and engraftment failure associated with infusion of a single cord blood
      unit. In DCBT, only one unit typically contributes to long-term hematopoiesis,
      but little is known about factors affecting cord predominance. As results from a
      phase I trial suggested that order of infusion may affect cord predominance, we
      analyzed the effect of preinfusion variables on chimerism patterns of 38 patients
      enrolled in the initial study and a subsequent phase II trial. All patients were
      treated with a reduced-intensity conditioning (RIC) regimen of fludarabine,
      melphalan and thymoglobulin followed by DCBT. By day 100, 66% of patients had
      hematopoiesis derived from a single cord blood unit. Higher post-thaw total
      nucleated cell and CD34+ cell dose were associated with cord predominance and in
      68% of patients (P=0.03); the predominant cord blood unit was infused first. Only
      the post-thaw CD34+ cell dose of the predominant unit predicted time to both
      neutrophil and platelet engraftment. Although based on a small number of
      patients, our results identify parameters that may affect cord predominance and
      engraftment in the setting of DCBT following RIC and suggest possible strategies
      for selecting infusion order for cord blood units.

PMID- 18037943
TI  - Stem cell transplantation for neuroblastoma.
AB  - High-risk neuroblastoma is a childhood malignancy with a poor prognosis. Gradual
      improvements in survival have correlated with therapeutic intensity, and the
      ability to harvest, process and store autologous hematopoietic stem cells has
      allowed for dose intensification beyond marrow tolerance. The use of high-dose
      chemotherapy with autologous hematopoietic stem cell rescue in consolidation has
      resulted in improvements in survival, although further advances are still needed.
      Newer approaches to SCT and supportive care, most notably the transition to PBSC,
      have resulted in further improvement in survival and decreases in treatment
      related mortality. Research into experimental approaches to hematopoietic SCT is
      ongoing.

PMID- 18037944
TI  - Reduced intensity conditioning and allogeneic stem cell transplantation in
      childhood malignant and nonmalignant diseases.
AB  - Allogeneic hematopoietic SCT is well established as a potentially curative
      therapy for children and adults with both malignant and nonmalignant diseases.
      However, myeloablative SCT is associated with significant short- and long-term
      complications. The goals of a reduced intensity-conditioning (RIC) regimen are to
      prevent graft rejection and establish stable donor-derived hematopoiesis at a
      level sufficient for cure of the underlying disease and, in patients with
      hematologic malignancy, to provide a GVL effect, while decreasing the short- and
      long-term complications associated with myeloablative conditioning therapy. RIC
      regimens have enabled SCT to be performed in children with preexisting
      comorbidities that preclude conventional conditioning. RIC-SCT has been most
      extensively studied in patients with nonmalignant disorders and for some of
      these, including primary immunodeficiencies and hemophagocytic
      lymphohistiocytosis, sufficient data now exist to support its routine use even in
      patients without comorbidity. Less data exist on RIC-SCT for children with
      hematologic malignancies and at present this should be restricted to children who
      are not candidates for, or have relapsed after, myeloablative SCT. Here we review
      available data on the use of RIC-SCT in pediatric patients, highlighting
      important clinical lessons and areas that require further study.

PMID- 18037945
TI  - Plasma HHV-6 viral load-guided preemptive therapy against HHV-6 encephalopathy
      after allogeneic stem cell transplantation: a prospective evaluation.
AB  - Human herpesvirus 6 (HHV-6) causes life-threatening encephalopathy in recipients
      of allogeneic SCT, but no consensus has been reached regarding appropriate
      preventive methods. This study evaluated a plasma HHV-6 viral load-guided
      preemptive approach against HHV-6-associated encephalopathy. Plasma real-time PCR
      assay was performed once a week. Among 29 patients, 19 developed positive plasma
      HHV-6 DNA. Median maximum plasma HHV-6 DNA was 4593.5 copies/ml plasma (range,
      150.0-127 891.0 copies/ml plasma). In one of eight events with low-level HHV-6
      DNA (defined as <1000 copies/ml plasma) and four of seven events with mid-level
      HHV-6 DNA (1000-9999.5 copies/ml plasma), HHV-6 loads in plasma subsequently
      continued increasing. Ganciclovir was administered against six of nine patients
      with high-level HHV-6 DNA (> or =10,000 copies/ml plasma). High-level HHV-6 DNA
      resolved similarly in both groups with or without ganciclovir therapy. Among the
      nine patients with high-level HHV-6 DNA two developed encephalopathy. As
      encephalopathy developed before the detection of high-level HHV-6 DNA in plasma,
      these two patients had not received preemptive ganciclovir therapy. In
      conclusion, our preemptive approach against HHV-6-associated encephalopathy
      cannot prevent all cases of HHV-6 encephalopathy in SCT recipients due to the
      dynamic kinetics of plasma HHV-6 viral load.

PMID- 18037946
TI  - Figuration of the real as an intersubjective process.
AB  - In this paper, I make use of the term figuration, which relates to the process of
      giving shape to unconscious contents in the form of meaningful presentations. My
      interest is in how traumatic experience succeeds or fails to become psychically
      figured and thereby susceptible to elaboration and absorption through
      intersubjective process. I argue that the process of figuration always occurs in
      an actual or implied intersubjective context and involves, thereby, a central
      feature of an exchange between subject and Other. These concepts are discussed
      and applied to a case report of an analytic psychotherapy involving a traumatic
      dream and its sequellae.

PMID- 18037948
TI  - Balint's influence on contemporary psychoanalytic theory and practice.
AB  - Invited by the Psychoanalytic Psychotherapy Study Center in New York to lecture
      on my book Michael Balint: Le renouveau de l'Ecole de Budapest, Toulouse, Eres
      2000, I first gave my personal and analytic motivations for writing this book.
      Then I stressed Balint's original contributions to analytical theory and
      practice: the object relation combined with the theory of instinct, the
      development of the infant, adolescent and even of old age, the basic fault,
      archaic defenses (such as ocnophilia and philobatism), as well as his idea about
      analytic treatment with its phases of regression and "new beginning". His style
      and his discretion in treatment and mainly the responsibility he recommended to
      the analysts seem to me very important not to forget. I have shown him as
      Ferenczi's heir and how he continued his work. His clinical approach and his
      style are evoked to alert contemporary analysts--who sometimes just know his
      method to train general practitioners through the Balint group--that they have
      been influenced unbeknown to them.

PMID- 18037949
TI  - Long-term psychoanalytic therapy as a life-saving procedure.
AB  - A dramatic long-term psychoanalytic treatment of a psychotic character disorder
      is presented in detail. This patient began therapy with a long standing history
      of an eating disorder for which she had received many hospitalizations and forms
      of treatment without any success. She was in a deep despair and as a last resort
      agreed to a psychoanalytic therapy. During the many years of treatment the eating
      disorder completely resolved but was replaced by a series of very dangerous
      accidents that occurred each time she was betrayed and disappointed by a boy
      friend. This went on pari passu with a deepening understanding of her childhood
      and her psychodynamics but the middle of the therapy was very stormy and required
      tenacious efforts to maintain the treatment. The self-destructive behavior was
      traced to early and profound childhood disappointments and a sense that these
      were her fault because she was so unlovable and therefore deserved punishment. A
      dangerous stalemate developed in the treatment after a number of years. The
      analyst presented the case to colleagues several times and wrote it up in detail,
      which enabled him to understand his own countertransference and resolve it. This
      resulted in a dramatic change in the patient and a very favorable and happy
      ending to this very difficult treatment after 15 years. Although the author
      believes all patients in psychoanalysis should be approached with as neutral and
      objective a stance as possible, emphasizing free association and dream material
      in order to interpret the crucial childhood determinants of the patient's
      psychopathology, in cases such as psychotic character disorders the outcome
      clearly also depends on interpersonal factors. The case illustrates the deep
      partly conscious and partly unconscious interaction between a patient and her
      analyst over many years of treatment and the profound effect this has on the
      outcome. It underscores the importance of patients being allowed to heal in their
      own way and in their own time without intrusion or interference from the analyst.
      It also demonstrates the crucial importance of long-term psychoanalytic therapy
      as a life-saving procedure in cases where it is appropriate in spite of the great
      amount of time and expense involved.

PMID- 18037950
TI  - Paradox and personal growth during crisis.
AB  - This paper considers situations of personal crisis, which lead to experiences of
      extreme helplessness and emotional upheaval. It is suggested that although crises
      may be precipitated by either external or internal events, all crisis situations
      have a common denominator. What is common to all crises is the disruption and
      then restitution of the ability to withstand paradox in the experience of the
      self. Although there is wide variety in the nature of the personal crisis, all
      crisis situations have similar structural features. Crises are so dramatic and so
      frequent a phenomenon in the human experience that they warrant serious and
      thorough investigation of their nature. Because crisis situations are on the one
      hand so disabling and potentially destructive and on the other hand can open
      doors to growth and development, they are extremely valuable to deepen our
      understanding of how crises develop and unfold.

PMID- 18037953
TI  - Owning it.
AB  - What is the distinction, if any, between who we are as people and what we believe
      and how we practice as psychoanalysts? For me, art played a vital affirmation
      that there was a world full of larger ideas and feelings in contrast to the
      desiccated environment my parents had created. From grade school, through my
      training as an analyst to the present, art has not only elucidated who I am but
      expanded my sense of being a creative individual. From the procession of viewing
      art and engaging with it, to making and acquiring art pieces, the discovery was
      not only that I owned these pieces but that their impact challenged the 'who' I
      thought I was if I was willing to own up to it. The information that informs our
      personal beliefs and practice in psychoanalysis comes from such an openness to
      new experiences from many directions in our daily lives, and challenges who we
      believe we are. Art adds to analytic knowledge, not by giving us an
      interpretation for our lives, but by stimulating the genuinely creative process
      of self-reflection.

PMID- 18037956
TI  - Mechanisms of androgen receptor activation in advanced prostate cancer:
      differential co-activator recruitment and gene expression.
AB  - Prostate tumour growth depends on androgens; hence treatment includes androgen
      ablation and anti-androgens. Eventually tumours progress and in approximately 30%
      of patients this is associated with mutation of the androgen receptor. Several
      receptor variants associated with advanced disease show promiscuous activation by
      other hormones and anti-androgens. Such loss of specificity could promote
      receptor activation, hence tumour growth, in the absence of conventional ligands,
      explaining therapy failure. We aimed to elucidate mechanisms by which alternative
      ligands promote receptor activation. The three most commonly identified variants
      in tumours (with amino-acid substitutions H874Y, T877A and T877S) and wild-type
      receptor showed differences in co-activator recruitment dependent upon ligand and
      the interaction motif utilized. Co-expression and knockdown of co-activators that
      bind via leucine or phenylalanine motifs, combined with chromatin
      immunoprecipitation and quantitative PCR, revealed these preferences extend to co
      activator recruitment in vivo and affect receptor activity at the transcriptional
      level, with subsequent effects on target gene regulation. The findings suggest
      that mutant receptors, activated by alternative ligands, drive growth via
      different mechanisms to androgen-activated wild-type receptor. Tumours may hence
      behave differently dependent upon any androgen receptor mutation present and what
      ligand is driving growth, as distinct subsets of genes may be regulated.

PMID- 18037957
TI  - Phospholipase C gamma 1 regulates the Rap GEF1-Rap1 signalling axis in the
      control of human prostate carcinoma cell adhesion.
AB  - Phospholipase Cgamma1 (PLCgamma1) is activated downstream of a variety of
      extracellular stimuli and has previously been implicated in the regulation of
      motility responses central to tumour cell invasion. In this study, we used a
      novel RNAi vector system to achieve conditional PLCgamma1 knockdown in PC3LN3
      human prostate carcinoma cells for further evaluation of PLCgamma1 in tumour cell
      biology. Using this approach, we revealed a role for PLCgamma1 in the regulation
      of PC3LN3 cell adhesion that appears to be independent of its effects on tumour
      cell chemotactic migration and spreading in response to extracellular matrix.
      Subsequent microarray analysis of PLCgamma1-knockdown cells revealed Rap GEF1
      mRNA to be decreased in response to PLCgamma1 loss. This translated into a
      decrease in Rap GEF1 protein levels and a significant loss of Rap1 activity in
      PLCgamma1-knockdown cells. Transient knockdown of Rap GEF1 caused a reduction in
      PC3LN3 adhesion while overexpression of Rap GEF1 rescued the PLCgamma1 knockdown
      induced adhesion defect. These data highlight control of the Rap GEF1-Rap1
      molecular switch as a specific requirement for PLCgamma1-mediated tumour cell
      adhesion.

PMID- 18037958
TI  - Reduced expression and tumor suppressor function of the ETS transcription factor
      ESE-3 in prostate cancer.
AB  - Deregulated expression of ETS transcription factors has emerged as an important
      event in prostate cancer pathogenesis. Here we show that the expression of
      epithelial-specific ETS (ESE)-3 factor is frequently reduced at the RNA and
      protein level in prostate cancer clinical samples compared to normal prostate. In
      PC3 and DU145 cells, ESE-3 was silenced by methylation of an evolutionarily
      conserved CpG site in its promoter and treatment with 5-aza-2'-deoxycytidine
      restored its expression. In a prostate epithelial cell transformation model,
      methylation of this site was inversely correlated with ESE-3 expression and
      occurred only in Ras-transformed and tumorigenic cells and not in normal and
      immortalized cells suggesting that ESE-3 silencing was functionally linked to
      oncogenic transformation. Consistent with a tumor suppressor function, re
      expression of ESE-3 in prostate cancer cells inhibited clonogenic survival and
      induced apoptotic cell death. ESE-3 increased the level of procaspase-3, a key
      element in the apoptotic cascade. This effect was mediated at the transcriptional
      level by direct binding of ESE-3 to the caspase-3 promoter. Collectively, our
      findings implicate ESE-3 as a candidate tumor suppressor in prostate cancer.
      Decreased expression of ESE-3 may result in loss of important regulatory
      mechanisms in prostate epithelial cells and contribute to the pathogenesis of
      prostate cancer.

PMID- 18037959
TI  - Physical and functional interactions between STAT3 and KAP1.
AB  - Signal transducers and activators of transcription (STATs) mediate cell
      proliferation, differentiation and survival in immune responses, hematopoiesis,
      neurogenesis and other biological processes. For example, STAT3 has been reported
      to be constitutively activated in numerous cancer cells. To clarify the molecular
      mechanisms underlying the STAT activation, we performed yeast two-hybrid
      screening and identified KAP1/TIF1beta as a novel STAT-binding partner. KAP1 is a
      universal corepressor protein for the Kruppel-associated box zinc-finger protein
      superfamily of transcriptional repressors. We found endogenous KAP1 associated
      with endogenous STAT3 in vivo. Importantly, small-interfering RNA-mediated
      reduction of KAP1 expression enhanced interleukin (IL)-6-induced STAT3-dependent
      transcription and gene expression. Furthermore, reduction of KAP1 expression
      resulted in the marked accumulation of STAT3 phosphorylated on Ser727 in the
      nucleus, a modification that regulates its transcriptional activation. These
      results indicate that KAP1 may serve as a transcriptional regulator of the IL
      6/STAT3 signaling pathway.

PMID- 18037960
TI  - Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in
      pancreatic cancer cells.
AB  - Pancreatic cancer still remains one of the most lethal diseases and establishment
      of new therapy is needed. The purpose of this study is to find novel factors
      involved in pancreatic cancer progression by proteomic approach. We compared pre-
      and postoperative serum protein profiling obtained from pancreatic cancer
      patients who had curative pancreatectomy using surface-enhanced laser desorption
      ionization time-of-flight mass spectrometry. The peak intensity levels of both
      6630 and 6420 Da were significantly higher in the preoperative serum than in the
      postoperative serum (P<0.002). Sequential amino acid analysis identified these
      proteins to be apolipoprotein C-1 (ApoC-1). The high level of ApoC-1 in
      preoperative serum significantly correlated with poor prognosis. Furthermore,
      ApoC-1 was abundantly expressed in pancreas neoplastic epithelium, and was
      detected in the culture medium of the pancreatic cancer cell line in vitro, which
      suggests that cancer cells secrete ApoC-1. Inhibition of ApoC-1 expression by
      short interfering RNA suppressed cell proliferation and induced apoptosis of
      pancreatic cancer cells. The specific expression of ApoC-1 and its role in
      preventing from spontaneous apoptosis in pancreatic cancer cells suggest that
      ApoC-1 contributes to the aggressiveness of pancreatic cancer and will be useful
      as a new therapeutic target.

PMID- 18037961
TI  - Glioblastoma-derived stem cell-enriched cultures form distinct subgroups
      according to molecular and phenotypic criteria.
AB  - Tumor cells with stem cell-like properties can be cultured from human
      glioblastomas by using conditions that select for the expansion of neural stem
      cells. We generated cell lines from glioblastoma specimens with the goal to
      obtain model systems for glioma stem cell biology. Unsupervised analysis of the
      expression profiles of nine cell lines established under neural stem cell
      conditions yielded two distinct clusters. Four cell lines were characterized by
      the expression of neurodevelopmental genes. They showed a multipotent
      differentiation profile along neuronal, astroglial and oligodendroglial lineages,
      grew spherically in vitro, expressed CD133 and formed highly invasive tumors in
      vivo. The other five cell lines shared expression signatures enriched for
      extracellular matrix-related genes, had a more restricted differentiation
      capacity, contained no or fewer CD133+ cells, grew semiadherent or adherent in
      vitro and displayed reduced tumorigenicity and invasion in vivo. Our findings
      show that stable, multipotent glioblastoma cell lines with a full stem-like
      phenotype express neurodevelopmental genes as a distinctive feature, which may
      offer therapeutic targeting opportunities. The generation of another distinct
      cluster of cell lines showing similarly homogeneous profiling but restricted stem
      cell properties suggests that different phenotypes exist, each of which may lead
      to the typical appearance of glioblastoma.

PMID- 18037962
TI  - The proline-rich domain in p63 is necessary for the transcriptional and apoptosis
      inducing activities of TAp63.
AB  - p63 shares considerable sequence identity with p53, especially in its DNA
      binding, activation and tetramerization domains. When the upstream promoter is
      used for p63 expression, three major transactivation p63 (TAp63) isoforms (alpha,
      beta and gamma) are produced. p63 is also expressed from an alternate promoter
      located in intron 3, producing three major DeltaNp63 isoforms. Recent studies
      demonstrated that p63 has the potential to function as a tumor suppressor or an
      oncoprotein. To further address this, we generated cell lines that inducibly
      express each TAp63 isoform. We showed that TAp63 isoforms are capable of inducing
      p53-responsive genes, inhibiting cell proliferation and promoting apoptosis.
      Interestingly, we discovered that both the activation domain (residues 1-59) and
      the proline-rich domain (residues 67-127) are required for TAp63 transcriptional
      activity. Likewise, TAp63beta(DeltaPRD), deleted of residues 60-133, possessed a
      greatly attenuated ability to induce endogenous target genes and promote
      apoptosis, but retained the ability to inhibit cell proliferation when expressed
      in stable, inducible cell lines. TAp63beta(DeltaPRD) also functioned as a
      dominant negative to wild-type p63beta in a dose-dependent manner. Furthermore,
      the loss of function seen with deletion of the proline-rich domain was not due to
      a DNA-binding defect, as TAp63beta(DeltaPRD) was found to strongly bind
      endogenous promoters using chromatin immunoprecipitation assay. Finally,
      mutational analysis revealed that a PXXP motif at residues 124-127 contributes to
      the transcriptional activity of TAp63. Altogether, our findings suggest that
      TAp63 transcriptional activity can be regulated by modification(s) of, or protein
      interactions with, the p63 proline-rich domain.

PMID- 18037963
TI  - The latent membrane protein 1 oncogene modifies B-cell physiology by regulating
      autophagy.
AB  - Epstein-Barr virus (EBV) is a herpes virus that is associated with several human
      cancers. Infection of B cells by EBV leads to their induction and maintenance of
      proliferation and requires the oncogene, latent membrane protein 1 (LMP1). LMP1
      signals in a ligand-independent manner and is expressed at widely different
      levels in cells of a single clone. It is this unusual distribution that allows
      LMP1 to stimulate multiple, distinct pathways. Average levels of LMP1 induce
      proliferation while high levels induce cytostasis and inhibition of protein
      synthesis. These inhibitory pathways are induced by the six transmembrane domains
      of LMP1. We uncovered a novel function encoded by transmembrane domains 3-6 of
      LMP1; they induce autophagy in a dose-dependent manner and thus, modify the
      physiology of their host. Cells that express low levels of LMP1 display early
      stages of autophagy, autophagosomes; those that express high levels of this
      oncogene display late stages of autophagy, autolysosomes. Inhibition of autophagy
      in EBV-positive cells leads to an accumulation of LMP1 and a decreased ability to
      form colonies. These results indicate that LMP1's induction of autophagy
      contributes to its own regulation and that of its host cell.

PMID- 18037964
TI  - The leukemogenic CALM/AF10 fusion protein alters the subcellular localization of
      the lymphoid regulator Ikaros.
AB  - The t(10;11)(p13;q14) translocation leads to the fusion of the CALM and AF10
      genes. This translocation can be found as the sole cytogenetic abnormality in
      acute lymphoblastic leukemia, acute myeloid leukemia and in malignant lymphomas.
      The expression of CALM/AF10 in primary murine bone marrow cells results in the
      development of an aggressive leukemia in a murine bone marrow transplantation
      model. Using a yeast two-hybrid screen, we identified the lymphoid regulator
      Ikaros as an AF10 interacting protein. Interestingly, Ikaros is required for
      normal development of lymphocytes, and aberrant expression of Ikaros has been
      found in leukemia. In a murine model, the expression of a dominant negative
      isoform of Ikaros causes leukemias and lymphomas. The Ikaros interaction domain
      of AF10 was mapped to the leucine zipper domain of AF10, which is required for
      malignant transformation both by the CALM/AF10 and the MLL/AF10 fusion proteins.
      The interaction between AF10 and Ikaros was confirmed by GST pull down and co
      immunoprecipitation. Coexpression of CALM/AF10 but not of AF10 alters the
      subcellular localization of Ikaros in murine fibroblasts. The transcriptional
      repressor activity of Ikaros is reduced by AF10. These results suggest that
      CALM/AF10 might interfere with normal Ikaros function, and thereby block lymphoid
      differentiation in CALM/AF10 positive leukemias.

PMID- 18037965
TI  - Influence of nucleophosmin/B23 on DNA binding and transcriptional activity of the
      androgen receptor in prostate cancer cell.
AB  - The promotion and progression of prostate cancer (PCa) are associated with
      androgen receptor (AR) signalling. AR functions are modulated by a variety of co
      factors amongst which we identified the nucleophosmin (NPM/B23), a member of the
      histone chaperone family. Here, we show that NPM is overexpressed in PCa compared
      to normal adjacent tissues. AR and NPM interact in vitro and in vivo, and NPM is
      critical for androgen-dependent transcriptional activation in LNCaP cells as an
      anti-NPM siRNA downregulates transcription of a transfected androgen response
      element (ARE)-containing reporter promoter as well as expression of the
      endogenous androgen responsive prostate-specific antigen (PSA) gene. By
      investigating the effect of NPM on AR, we have also observed that NPM enhances AR
      binding to an ARE in vitro in electrophoretic gel mobility-shift assay
      experiments. Chromatin immunoprecipitation studies further demonstrated that both
      AR and NPM associate with AREs of the PSA gene in vivo. Altogether, our data
      suggest that the molecular histone chaperone NPM could regulate AR functions by
      promoting assembly of AR-containing regulatory complexes and that high levels of
      NPM might alter AR functions in PCa.

PMID- 18037966
TI  - Thyroid hormone receptor-beta (TR beta 1) impairs cell proliferation by the
      transcriptional inhibition of cyclins D1, E and A2.
AB  - Thyroid hormone receptor-beta1 (TRbeta1) belongs to the ligand-inducible
      transcription factor superfamily. We have previously described that stable
      TRbeta1 expression impairs fibroblast proliferation diminishing levels and
      activity of the main regulators of the G(1)/S transition. To unmask the
      underlying molecular mechanism of this action, we have investigated the
      expression of cyclin D1, E and A2 upon serum stimulation in TRbeta1 expressing
      cells, finding a strong downregulation of their mRNAs, concomitant with low
      protein levels. The inhibition of the transcriptional activation in response to
      serum of these cyclins is differently exerted. For cyclin D1, we demonstrate that
      TRbeta1 represses its promoter as a consequence of the downregulation of c-jun
      levels, diminished AP-1 activation and loss of c-jun recruitment to its binding
      sites on cyclin D1 promoter. For cyclin E and A2, it is the impairment of the
      cyclinD/Rb/E2F pathway by TRbeta1 that prevents the activation of these two E2F
      target genes. Indeed, recruitment of E2F-1 to cyclin A2 promoter could not be
      detected. In summary, we propose that apo-TRbeta1 exerts its antiproliferative
      action through a mechanism that could constitute a model by which other nuclear
      receptors may control cell division.

PMID- 18037967
TI  - Inactivation of the Rb pathway and overexpression of both isoforms of E2F3 are
      obligate events in bladder tumours with 6p22 amplification.
AB  - E2F3 and CDKAL1 are candidate genes from the 6p22 region frequently amplified in
      bladder cancer. Expression of E2F3 isoforms (E2F3a and b) and CDKAL1 were
      examined and modulated in 6p22-amplified bladder cell lines. Eight lines with
      amplification showed overexpression of both E2F3 isoforms and CDKAL1. shRNA
      mediated knockdown of CDKAL1 had no effect on proliferation. Knockdown of E2F3a
      or E2F3b alone induced antiproliferative effects, with the most significant
      effect on proliferation being observed when both isoforms were knocked down
      together. As E2Fs interact with the Rb tumour suppressor protein, Rb expression
      was analysed. There was a striking relationship between 6p22.3 amplification,
      E2F3 overexpression and lack of Rb expression. This was also examined in primary
      bladder tumours. Array-CGH detected 6p22.3 amplification in 8/91 invasive
      tumours. Five were studied in more detail. Four showed 13q14.2 loss (including
      RB1) and expressed no Rb protein. In the fifth, 13q was unaltered but the CDKN2A
      locus was deleted. This tumour was negative for p16 and positive for Rb protein.
      As p16 is a negative regulator of the Rb pathway, its loss represents an
      alternative mechanism for inactivation. Indeed, a phospho-specific Rb antibody
      showed much Rb protein in a hyperphosphorylated (inactive) form. We conclude that
      inactivation of the Rb pathway is required in addition to E2F3 overexpression in
      this subset of bladder tumours.

PMID- 18037970
TI  - Single Scan 2D NMR Spectroscopy on a 25 T Bitter Magnet.
AB  - 2D NMR relies on monitoring systematic changes in the phases incurred by spin
      coherences as a function of an encoding time t(1), whose value changes over the
      course of independent experiments. The intrinsic multiscan nature of such
      protocols implies that resistive and/or hybrid magnets, capable of delivering the
      highest magnetic field strengths but possessing poor temporal stabilities, become
      unsuitable for 2D NMR acquisitions. It is here shown with a series of homo- and
      hetero-nuclear examples that such limitations can be bypassed using recently
      proposed 2D "ultrafast" acquisition schemes, which correlate interactions along
      all spectral dimensions within a single scan.

PMID- 18037968
TI  - Insulin decreases inflammatory signal transcription factor expression in primary
      human liver cells after LPS challenge.
AB  - Hepatic homeostasis is essential for survival in critically ill and burned
      patients. Insulin administration improves survival and decreases infections in
      these patients. To determine the molecular mechanisms, the aim of the present
      study was to establish a stress model using primary human hepatocytes (PHHs) and
      to study the effects of insulin on the hepatic inflammatory signaling cascade.
      Liver tissue was obtained from general surgical patients, and PHHs were isolated
      and maintained in culture. Primary hepatocyte cultures were challenged with
      various doses of lipopolysaccharide (LPS), and the inflammatory signal
      transcription cascade was determined by real-time PCR. In subsequent experiments,
      primary hepatocyte cultures were challenged with LPS and insulin was added in
      various doses. Glucose was determined by colorimetric assays. PHHs treated with
      100 microg/mL LPS showed a profound inflammatory reaction with increased
      expression of interleukin (IL)-6, IL-10, IL-1beta, tumor necrosis factor (TNF),
      and signal transducer and activator of transcription 5 (STAT-5). Insulin at 10
      IU/mL significantly decreased IL-6, TNF, and IL-1beta at pretranslational levels,
      an effect associated with decreased STAT-5 mRNA expression (P < 0.05). Glucose
      concentration and cellular metabolic activity were not different between controls
      and insulin-treated cells. Based on our results, we suggest that primary
      hepatocyte cultures can be used to study the effect of LPS on the inflammatory
      cascade. Insulin decreases hepatic cytokine expression, which is associated with
      decreased STAT-5 expression.

PMID- 18037969
TI  - Neoplastic transformation of human small airway epithelial cells induced by
      arsenic.
AB  - Human small airway epithelial cells (SAECs) previously immortalized with human
      telomerase reverse transcriptase (h-TERT) were continuously treated with sodium
      arsenite at a dose of 0.5 microg/mL in culture for up to 6 months. Arsenic
      treated cells progressively displayed an increase in transformed phenotype
      including enhanced growth saturation density, plating efficiency, and anchorage
      independent growth and invasion capability compared with their nontreated control
      cells. To determine whether arsenic-induced cell transformation was associated
      with genomic instability, treated and control cells were also analyzed for
      micronuclei formation. A 4.8-fold increase in micronuclei incidence in arsenic
      treated cells was detected in conjunction with increased N-phosphonacetyl-l
      aspartate (PALA)-resistant characteristics. In addition, arsenic-treated cells
      showed an increase in c-H-ras, c-myc, and c-fos protein expression relative to
      controls. The change in oncoprotein expression correlated with a decrease in wild
      type p53 expression and hyperphosphorylated retinoblastoma. Taken together, these
      results strongly suggest that h-TERT immortalized human small airway epithelial
      cells underwent step-wise transformation after inorganic arsenic treatment.

PMID- 18037971
TI  - 3-D Quantum Transport Solver Based on the Perfectly Matched Layer and Spectral
      Element Methods for the Simulation of Semiconductor Nanodevices.
AB  - A 3-D quantum transport solver based on the spectral element method (SEM) and
      perfectly matched layer (PML) is introduced to solve the 3-D Schrodinger equation
      with a tensor effective mass. In this solver, the influence of the environment is
      replaced with the artificial PML open boundary extended beyond the contact
      regions of the device. These contact regions are treated as waveguides with known
      incident waves from waveguide mode solutions. As the transmitted wave function is
      treated as a total wave, there is no need to decompose it into waveguide modes,
      thus significantly simplifying the problem in comparison with conventional open
      boundary conditions. The spectral element method leads to an exponentially
      improving accuracy with the increase in the polynomial order and sampling points.
      The PML region can be designed such that less than -100 dB outgoing waves are
      reflected by this artificial material. The computational efficiency of the SEM
      solver is demonstrated by comparing the numerical and analytical results from
      waveguide and plane-wave examples, and its utility is illustrated by multiple
      terminal devices and semiconductor nanotube devices.

PMID- 18037973
TI  - Reductive Deprotection of Silyl Groups with Wilkinson's Catalyst/Catechol Borane.
AB  - Traditionally silyl groups are deprotected with acids and fluorides. These
      methods are, however, less discriminating when multi-silyl groups are present in
      the same molecule resulting in lower yields of desired products. The manipulation
      of these functions during the total synthesis of natural products, e.g.
      prostaglandins and isoprostanes, requires the selective protection and
      deprotection of these groups.We are reporting here on a mild, selective and
      efficient method for the reductive deprotection of silyl groups using Wilkinson's
      catalyst/catechol borane or catechol borane alone.

PMID- 18037972
TI  - Synthesis of porphyrins bearing 1-4 hydroxymethyl groups and other one-carbon
      oxygenic substituents in distinct patterns.
AB  - Porphyrins that bear one-carbon oxygenic substituents (hydroxymethyl, formyl,
      ester) directly attached to the macrocycle afford a compact architecture that is
      attractive for diverse applications. Routes to 9 porphyrins bearing such groups
      in distinct architectures (A(4)-, trans-A(2)-, trans-A(2)B(2)-, trans-AB- and
      trans-AB(2)C-porphyrins) have been explored (A = hydroxymethyl), including
      porphyrins bearing two one-carbon units in different oxidation states
      (hydroxymethyl/ester, formyl/ester). The hydroxymethyl group was introduced via
      TBDMS-protected dipyrromethane precursors.

PMID- 18037974
TI  - New access to H-phosphonates via metal-catalyzed phosphorus-oxygen bond
      formation.
AB  - A novel approach to H-phosphonates from hypophosphorous acid using a transfer
      hydrogenation process was developed. This method is atom-economical,
      environmentally friendly, catalytic, and efficient, leading easily to H
      phosphonate monoesters or ammonium salt in moderate to good yields.

PMID- 18037975
TI  - Finite Element Simulation of Elastohydrodynamic Lubrication of Soft Biological
      Tissues.
AB  - In the serosal cavities (e.g. pleural, pericardial) soft tissues slide against
      each other, lubricated by thin fluid. We used rotational devices to study the
      tribology of such tissues, which appear to exhibit mixed and hydrodynamic
      lubrication. To explore mechanism, we modeled the interaction of fluid and soft
      material in 3D using a simple cylindrical geometry with an uneven solid-fluid
      interface in rotation. Deformation of the solid, frictional force, and fluid
      thickness are presented as a function of applied rotational velocity, applied
      normal load and material properties. The results suggest that the deformation
      caused by hydrodynamic pressure leads to load-supporting behavior.

PMID- 18037976
TI  - Performance of the U.S. Office of Management and Budget's Revised Race and
      Ethnicity Categories in Asian Populations*
AB  - OBJECTIVES: The U.S. Office of Management and Budget (OMB) guidelines for
      collecting and reporting race and ethnicity information recently divided the
      "Asian or Pacific Islander" category into "Asian" and "Native Hawaiian or Other
      Pacific Islander". The OMB's decision to disaggregate the "Asian or Pacific
      Islander" category was the first step toward providing these communities with
      information to better serve their needs. However, whether individuals who
      formerly made up the combined group categorize themselves as the new guidelines
      intend is a question analyzed in this report.  METHODS: A subset of adults
      participating in the Hemochromatosis and Iron Overload Screening Study completed
      both the OMB-minimum and the expanded race and ethnicity measure used in the
      National Health Interview Survey. We compared responses on the expanded measure
      contained within the OMB "Asian" definition (Filipino, Korean, Vietnamese,
      Japanese, Asian Indian, Chinese, and/or Other Asian) to "Asian" responses on the
      OMB-minimum measure.  RESULTS: Mixed heritage Asians less often marked "Asian".
      Among mixed heritage Japanese, Chinese, and Filipinos, 27%, 49%, and 52% did not
      mark "Asian" on the OMB measure, respectively. Eleven percent of single-heritage
      Filipinos did not mark "Asian."  CONCLUSIONS: Many individuals formerly making up
      the combined "Asian or Pacific Islander" group do not categorize themselves as
      the revised OMB guidelines intend. This is particularly evident among Filipinos
      and among Asians of mixed heritage. This research illuminates the reliability and
      utility of the broad "Asian" category and points to possible consequences of
      collapsing groups into a single category, i.e., missed information and/or
      erroneous generalization.

PMID- 18037977
TI  - A Laplacian-based MMSE estimator for speech enhancement.
AB  - This paper focuses on optimal estimators of the magnitude spectrum for speech
      enhancement. We present an analytical solution for estimating in the MMSE sense
      the magnitude spectrum when the clean speech DFT coefficients are modeled by a
      Laplacian distribution and the noise DFT coefficients are modeled by a Gaussian
      distribution. Furthermore, we derive the MMSE estimator under speech presence
      uncertainty and a Laplacian statistical model. Results indicated that the
      Laplacian-based MMSE estimator yielded less residual noise in the enhanced speech
      than the traditional Gaussian-based MMSE estimator. Overall, the present study
      demonstrates that the assumed distribution of the DFT coefficients can have a
      significant effect on the quality of the enhanced speech.

PMID- 18037978
TI  - Quantile Stratification Based on a Misspecified Propensity Score in Longitudinal
      Treatment Effectiveness Analyses of Ordinal Doses.
AB  - The propensity adjustment provides a strategy to reduce the bias in treatment
      effectiveness analyses that compare non-equivalent groups such as seen in
      observational studies (Rosenbaum and Rubin, 1983). The objective of this
      simulation study is to examine the effect of omitting confounding variables from
      the propensity score on the quintile-stratified propensity adjustment in a
      longitudinal study. The primary focus was the impact of a misspecified propensity
      score on bias. Three features of the omitted confounding variables were examined:
      type of predictor variable (binary vs. continuous), constancy over time (time
      varying vs. time-invariant), and magnitude of the association with treatment and
      outcome (null, small, and large odds ratios). The simulation results indicate
      that omission of continuous, time-varying confounders that are strongly
      associated with treatment and outcome (i.e., an odds ratio of 1.75) adversely
      impacts bias, coverage, and type I error. Omitted time-varying continuous
      variables had somewhat more effect on bias than omitted binary variables. Time
      invariant confounding variables that are not included in the propensity score
      have a much less effect on results. This evaluation only examined continuous
      treatment effectiveness outcomes and the propensity scores used for
      stratification included just four variables. Relative to the use of the
      propensity adjustment in applied settings that typically comprise numerous
      potential confounding variables, the impact of one omitted continuous, time
      varying confound in this simulation study could be overstated.

PMID- 18037979
TI  - The influence of childhood maltreatment on adolescents' academic performance.
AB  - Evidence that childhood maltreatment is associated with emotional and behavioral
      problems throughout childhood suggests that maltreatment could lead to impaired
      academic performance in middle and high school. This article explores these
      effects using data on siblings. An index measure of the intensity of childhood
      maltreatment was included as a covariate in multivariate analyses of adolescents'
      risk for school performance impairments. Family fixed effects were used to
      control for unobservables linked to family background and neighborhood effects.
      More intense childhood maltreatment was associated with greater probability of
      having a low GPA (P=0.001) and problems completing homework assignments
      (P=0.007). Associations between maltreatment intensity and adolescent school
      performance were not sensitive to model specification. Additional analyses
      suggested that maltreatment effects are moderated by cognitive deficits related
      to attention problems. The implications of these findings for educators and
      schools are discussed.

PMID- 18037980
TI  - Gradiency and Visual Context in Syntactic Garden-Paths.
AB  - Through recording the streaming x, y coordinates of computer-mouse movements, we
      report evidence that visual context provides an immediate constraint on the
      resolution of syntactic ambiguity in the visual-world paradigm. This finding
      converges with previous eye-tracking results that support a constraint-based
      account of sentence processing, in which multiple partially-active syntactic
      alternatives compete against one another with the help of not only syntactic,
      semantic, and statistical factors, but also nonlinguistic factors such as visual
      context. Eye-tracking results in the visual-world paradigm are consistent with
      theories that posit limited interaction between context and syntax, but they are
      still consistent with related theories that allow immediate interaction but
      require serial pursuit of syntactic structures, such as the unrestricted race
      model. To tease apart the constraint-based and unrestricted-race accounts of
      sentence processing, the distribution of computer-mouse trajectories was analyzed
      for evidence of two populations of trials: those where only the correct parse was
      pursued and those where only the incorrect parse was pursued. We found no
      evidence of bimodality in the distribution of trajectory curvatures. Simulations
      with a constraint-based model produced trajectories that matched the human data.
      A nonlinguistic control study demonstrated the mouse-tracking paradigm's ability
      to elicit bimodal distributions of trajectory curvatures in certain experimental
      conditions. With effects of context posing a challenge for syntax-first models,
      and the absence of bimodality in the distribution of garden-path magnitude posing
      a challenge for unrestricted-race models, these converging methods support the
      constraint-based theory's account that the reason diverse contextual factors are
      able to bias one or another parse at the point of ambiguity is because those
      syntactic alternatives are continually partially-active in parallel, not
      discretely winnowed.

PMID- 18037981
TI  - Turing pattern outside of the Turing domain.
AB  - There are two simple solutions to reaction-diffusion systems with limit-cycle
      reaction kinetics, producing oscillatory behaviour. The reaction parameter mu
      gives rise to a 'space-invariant' solution, and mu versus the ratio of the
      diffusion coefficients gives rise to a 'time-invariant' solution. We consider the
      case where both solution types may be possible. This leads to a refinement of the
      Turing model of pattern formation. We add convection to the system and
      investigate its effect. More complex solutions arise that appear to combine the
      two simple solutions. The convective system sheds light on the underlying
      behaviour of the diffusive system.

PMID- 18037982
TI  - Integration of Trench-Isolated Through-Wafer Interconnects with 2D Capacitive
      Micromachined Ultrasonic Transducer Arrays.
AB  - This paper presents a method to provide electrical connection to a 2D capacitive
      micromachined ultrasonic transducer (CMUT) array. The interconnects are processed
      after the CMUTs are fabricated on the front side of a silicon wafer. Connections
      to array elements are made from the back side of the substrate via highly
      conductive silicon pillars that result from a deep reactive ion etching (DRIE)
      process. Flip-chip bonding is used to integrate the CMUT array with an integrated
      circuit (IC) that comprises the front-end circuits for the transducer and
      provides mechanical support for the trench-isolated array elements. Design,
      fabrication process and characterization results are presented. The advantages
      when compared to other through-wafer interconnect techniques are discussed.

PMID- 18037983
TI  - Differentiation of chiral phosphorus enantiomers by P and H NMR spectroscopy
      using amino acid derivatives as chemical solvating agents.
AB  - The ability of commercially available amino acid derivatives, especially Fmoc
      Trp(Boc)-OH, to differentiate enantiomers of chiral phosphonates, phosphinates,
      phosphates, phosphine oxides, and phosphonamidates is demonstrated with (31)P,
      (13)C, and (1)H NMR spectroscopy. The chiral differentiation provided a rapid and
      convenient method for measuring the enantiomeric purity of these phosphorus
      compounds.

PMID- 18037984
TI  - Advances in Magnetic Resonance Imaging for the assessment of degenerative disc
      disease of the lumbar spine.
AB  - The intervertebral disc is characterized by a tension-resisting annulus fibrosus,
      and a compression-resisting nucleus pulposus composed largely of proteoglycan.
      Both the annulus and the nucleus function in concert to provide the disc with
      mechanical stability. Early disc degeneration begins in the nucleus with
      proteoglycan depletion. Quantitative MRI techniques have been developed to non
      invasively quantify the earliest degenerative changes that occur within the disc.
      Our ability to identify and quantify these early biochemical changes will provide
      a better understanding of the pathophysiology of disc degeneration and facilitate
      the study of interventions that aim to halt or reverse the degenerative process.

PMID- 18037985
TI  - Sample Tracking in an Automated Cytogenetic Biodosimetry Laboratory for Radiation
      Mass Casualties.
AB  - Chromosome aberration-based dicentric assay is expected to be used after mass
      casualty life-threatening radiation exposures to assess radiation dose to
      individuals. This will require processing of a large number of samples for
      individual dose assessment and clinical triage to aid treatment decisions. We
      have established an automated, high-throughput, cytogenetic biodosimetry
      laboratory to process a large number of samples for conducting the dicentric
      assay using peripheral blood from exposed individuals according to
      internationally accepted laboratory protocols (i.e., within days following
      radiation exposures). The components of an automated cytogenetic biodosimetry
      laboratory include blood collection kits for sample shipment, a cell viability
      analyzer, a robotic liquid handler, an automated metaphase harvester, a metaphase
      spreader, high-throughput slide stainer and coverslipper, a high-throughput
      metaphase finder, multiple satellite chromosome-aberration analysis systems, and
      a computerized sample tracking system. Laboratory automation using commercially
      available, off-the-shelf technologies, customized technology integration, and
      implementation of a laboratory information management system (LIMS) for
      cytogenetic analysis will significantly increase throughput.This paper focuses on
      our efforts to eliminate data transcription errors, increase efficiency, and
      maintain samples' positive chain-of-custody by sample tracking during sample
      processing and data analysis. This sample tracking system represents a "beta"
      version, which can be modeled elsewhere in a cytogenetic biodosimetry laboratory,
      and includes a customized LIMS with a central server, personal computer
      workstations, barcode printers, fixed station and wireless hand-held devices to
      scan barcodes at various critical steps, and data transmission over a private
      intra-laboratory computer network. Our studies will improve diagnostic
      biodosimetry response, aid confirmation of clinical triage, and medical
      management of radiation exposed individuals.

PMID- 18037986
TI  - Thin film voltammetry of metabolic enzymes in rat liver microsomes.
AB  - We report herein thin film voltammetry and kinetics of electron transfer for
      redox proteins in rat liver microsomes for the first time. Films were made layer
      by-layer from liver microsomes and polycations on pyrolytic graphite electrodes.
      Cyclic voltammograms were chemically reversible with a midpoint potential of 
      0.48 V vs SCE at 0.1 V s(-1) in pH 7.0 phosphate buffer. Reduction peak
      potentials shifted negative at higher scan rates, and oxidation-reduction peak
      current ratios were approximately 1 consistent with non-ideal quasireversible
      thin film voltammetry. Analysis of oxidation-reduction peak separations gave an
      average apparent surface electron transfer rate constant of 30 s(-1). Absence of
      significant electrocatalytic reduction of O(2) or H(2)O(2) and lack of shift in
      midpoint potential when CO is added that indicates lack of an iron heme cofactor
      suggest that peaks can be attributed to oxidoreductases present in the microsomes
      rather than cytochrome P450 enzymes.

PMID- 18037987
TI  - Smoking Behavior and Demographic Risk Factors in Argentina: A Population-Based
      Survey.
AB  - BACKGROUND: Demographic and socioeconomic factors associated with smoking
      behavior were evaluated in a nationwide household survey in Argentina to describe
      the status of the tobacco epidemic. METHODS: Face-to-face interviews with adults,
      age 20 and older, assessed smoking status, frequency, and age of initiation.
      Multivariate logistic regression was used to compare social and demographic
      characteristics. RESULTS: Of the 43,863 participants, 38% of men and 24% of women
      were current smokers, and 20% of current smokers smoked occasionally. For older
      men and women, smoking was less prevalent and their probability of quitting
      higher. Men with more than high school education were less likely to be current
      smokers. Rates for women did not differ by education. CONCLUSIONS: The lower
      smoking rates among men with more education suggest that Argentina has begun to
      transition to the next stage of the tobacco epidemic. Tobacco control policy must
      direct efforts to change smoking behavior.

PMID- 18037988
TI  - The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents
      murine doxorubicin cardiomyopathy.
AB  - The clinical utility of anthracycline anticancer agents, especially doxorubicin,
      is limited by a progressive toxic cardiomyopathy linked to mitochondrial damage
      and cardiomyocyte apoptosis. Here we demonstrate that the post-doxorubicin mouse
      heart fails to upregulate the nuclear program for mitochondrial biogenesis and
      its associated intrinsic antiapoptosis proteins, leading to severe mitochondrial
      DNA (mtDNA) depletion, sarcomere destruction, apoptosis, necrosis, and excessive
      wall stress and fibrosis. Furthermore, we exploited recent evidence that
      mitochondrial biogenesis is regulated by the CO/heme oxygenase (CO/HO) system to
      ameliorate doxorubicin cardiomyopathy in mice. We found that the myocardial
      pathology was averted by periodic CO inhalation, which restored mitochondrial
      biogenesis and circumvented intrinsic apoptosis through caspase-3 and apoptosis
      inducing factor. Moreover, CO simultaneously reversed doxorubicin-induced loss of
      DNA binding by GATA-4 and restored critical sarcomeric proteins. In isolated rat
      cardiac cells, HO-1 enzyme overexpression prevented doxorubicin-induced mtDNA
      depletion and apoptosis via activation of Akt1/PKB and guanylate cyclase, while
      HO-1 gene silencing exacerbated doxorubicin-induced mtDNA depletion and
      apoptosis. Thus doxorubicin disrupts cardiac mitochondrial biogenesis, which
      promotes intrinsic apoptosis, while CO/HO promotes mitochondrial biogenesis and
      opposes apoptosis, forestalling fibrosis and cardiomyopathy. These findings imply
      that the therapeutic index of anthracycline cancer chemotherapeutics can be
      improved by the protection of cardiac mitochondrial biogenesis.

PMID- 18037989
TI  - Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in
      mice.
AB  - Transgenic expression of the abnormal products of acute myeloid leukemia
      associated (AML-associated) primary chromosomal translocations in hematopoietic
      stem/progenitor cells initiates leukemogenesis in mice, yet additional mutations
      are needed for leukemia development. We report here aberrant expression of PR
      domain containing 16 (PRDM16) in AML cells with either translocations of 1p36 or
      normal karyotype. These carried, respectively, relatively high prevalence of
      mutations in the TP53 tumor suppressor gene and in the nucleophosmin (NPM) gene,
      which regulates p53. Two protein isoforms are expressed from PRDM16, which differ
      in the presence or absence of the PR domain. Overexpression of the short isoform,
      sPRDM16, in mouse bone marrow induced AML with full penetrance, but only in the
      absence of p53. The mouse leukemias were characterized by multilineage cellular
      abnormalities and megakaryocyte dysplasia, a common feature of human AMLs with
      1p36 translocations or NPM mutations. Overexpression of sPRDM16 increased the
      pool of HSCs in vivo, and in vitro blocked myeloid differentiation and prolonged
      progenitor life span. Loss of p53 augmented the effects of sPRDM16 on stem cell
      number and induced immortalization of progenitors. Thus, overexpression of
      sPRDM16 induces abnormal growth of stem cells and progenitors and cooperates with
      disruption of the p53 pathway in the induction of myeloid leukemia.

PMID- 18037990
TI  - Heterotaxy and complex structural heart defects in a mutant mouse model of
      primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder
      associated with ciliary defects and situs inversus totalis, the complete mirror
      image reversal of internal organ situs (positioning). A variable incidence of
      heterotaxy, or irregular organ situs, also has been reported in PCD patients, but
      it is not known whether this is elicited by the PCD-causing genetic lesion. We
      studied a mouse model of PCD with a recessive mutation in Dnahc5, a dynein gene
      commonly mutated in PCD. Analysis of homozygous mutant embryos from 18 litters
      yielded 25% with normal organ situs, 35% with situs inversus totalis, and 40%
      with heterotaxy. Embryos with heterotaxy had complex structural heart defects
      that included discordant atrioventricular and ventricular outflow situs and
      atrial/pulmonary isomerisms. Variable combinations of a distinct set of
      cardiovascular anomalies were observed, including superior-inferior ventricles,
      great artery alignment defects, and interrupted inferior vena cava with azygos
      continuation. The surprisingly high incidence of heterotaxy led us to evaluate
      the diagnosis of PCD. PCD was confirmed by EM, which revealed missing outer
      dynein arms in the respiratory cilia. Ciliary dyskinesia was observed by
      videomicroscopy. These findings show that Dnahc5 is required for the
      specification of left-right asymmetry and suggest that the PCD-causing Dnahc5
      mutation may also be associated with heterotaxy.

PMID- 18037991
TI  - Maternal exposure to polycyclic aromatic hydrocarbons diminishes murine ovarian
      reserve via induction of Harakiri.
AB  - Maternal smoking during pregnancy is associated with a variety of adverse
      neonatal outcomes including altered reproductive performance. Herein we provide
      molecular evidence for a pathway involved in the elimination of the female
      germline due to prepregnancy and/or lactational exposure to polycyclic aromatic
      hydrocarbons (PAHs), environmental toxicants found in cigarette smoke. We show
      that ovaries of offspring born to mice exposed to PAHs contained only a third of
      the ovarian follicle pool compared with offspring of unexposed female mice.
      Activation of the cell death pathway in immature follicles of exposed females was
      mediated by the aryl hydrocarbon receptor (Ahr), as ovarian reserve was fully
      rescued by maternal cotreatment with the Ahr antagonist, resveratrol, or by
      inactivation of the Ahr gene. Furthermore, in response to PAHs, Ahr-mediated
      activation of the harakiri, BCL2 interacting protein (contains only BH3 domain),
      was necessary for execution of cell death. This pathway appeared to be conserved
      between mouse and human, as xenotransplanted human ovarian cortex exposed to PAHs
      responded by activation of the identical cell death cascade. Our data indicate
      that maternal exposure to PAHs prior to pregnancy and/or during lactation
      compromises ovarian reserve of female offspring, raising the concern about the
      transgenerational impact of maternal smoking on ovarian function in the human.

PMID- 18037993
TI  - Visual phenotype in Williams-Beuren syndrome challenges magnocellular theories
      explaining human neurodevelopmental visual cortical disorders.
AB  - Williams-Beuren syndrome (WBS), a neurodevelopmental genetic disorder whose
      manifestations include visuospatial impairment, provides a unique model to link
      genetically determined loss of neural cell populations at different levels of the
      nervous system with neural circuits and visual behavior. Given that several of
      the genes deleted in WBS are also involved in eye development and the
      differentiation of retinal layers, we examined the retinal phenotype in WBS
      patients and its functional relation to global motion perception. We discovered a
      low-level visual phenotype characterized by decreased retinal thickness, abnormal
      optic disk concavity, and impaired visual responses in WBS patients compared with
      age-matched controls by using electrophysiology, confocal and coherence in vivo
      imaging with cellular resolution, and psychophysics. These mechanisms of
      impairment are related to the magnocellular pathway, which is involved in the
      detection of temporal changes in the visual scene. Low-level magnocellular
      performance did not predict high-level deficits in the integration of motion and
      3D information at higher levels, thereby demonstrating independent mechanisms of
      dysfunction in WBS that will require remediation strategies different from those
      used in other visuospatial disorders. These findings challenge neurodevelopmental
      theories that explain cortical deficits based on low-level magnocellular
      impairment, such as regarding dyslexia.

PMID- 18037992
TI  - Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to
      mesenchymal transition.
AB  - Hypoxia has been proposed as an important microenvironmental factor in the
      development of tissue fibrosis; however, the underlying mechanisms are not well
      defined. To examine the role of hypoxia-inducible factor-1 (HIF-1), a key
      mediator of cellular adaptation to hypoxia, in the development of fibrosis in
      mice, we inactivated Hif-1alpha in primary renal epithelial cells and in proximal
      tubules of kidneys subjected to unilateral ureteral obstruction (UUO) using Cre
      loxP-mediated gene targeting. We found that Hif-1alpha enhanced epithelial-to
      mesenchymal transition (EMT) in vitro and induced epithelial cell migration
      through upregulation of lysyl oxidase genes. Genetic ablation of epithelial Hif
      1alpha inhibited the development of tubulointerstitial fibrosis in UUO kidneys,
      which was associated with decreased interstitial collagen deposition, decreased
      inflammatory cell infiltration, and a reduction in the number of fibroblast
      specific protein-1-expressing (FSP-1-expressing) interstitial cells. Furthermore,
      we demonstrate that increased renal HIF-1alpha expression is associated with
      tubulointerstitial injury in patients with chronic kidney disease. Thus, we
      provide clinical and genetic evidence that activation of HIF-1 signaling in renal
      epithelial cells is associated with the development of chronic renal disease and
      may promote fibrogenesis by increasing expression of extracellular matrix
      modifying factors and lysyl oxidase genes and by facilitating EMT.

PMID- 18037994
TI  - Nuclear receptors PPARbeta/delta and PPARalpha direct distinct metabolic
      regulatory programs in the mouse heart.
AB  - In the diabetic heart, chronic activation of the PPARalpha pathway drives
      excessive fatty acid (FA) oxidation, lipid accumulation, reduced glucose
      utilization, and cardiomyopathy. The related nuclear receptor, PPARbeta/delta, is
      also highly expressed in the heart, yet its function has not been fully
      delineated. To address its role in myocardial metabolism, we generated transgenic
      mice with cardiac-specific expression of PPARbeta/delta, driven by the myosin
      heavy chain (MHC-PPARbeta/delta mice). In striking contrast to MHC-PPARalpha
      mice, MHC-PPARbeta/delta mice had increased myocardial glucose utilization, did
      not accumulate myocardial lipid, and had normal cardiac function. Consistent with
      these observed metabolic phenotypes, we found that expression of genes involved
      in cellular FA transport were activated by PPARalpha but not by PPARbeta/delta.
      Conversely, cardiac glucose transport and glycolytic genes were activated in MHC
      PPARbeta/delta mice, but repressed in MHC-PPARalpha mice. In reporter assays, we
      showed that PPARbeta/delta and PPARalpha exerted differential transcriptional
      control of the GLUT4 promoter, which may explain the observed isotype-specific
      effects on glucose uptake. Furthermore, myocardial injury due to
      ischemia/reperfusion injury was significantly reduced in the MHC-PPARbeta/delta
      mice compared with control or MHC-PPARalpha mice, consistent with an increased
      capacity for myocardial glucose utilization. These results demonstrate that
      PPARalpha and PPARbeta/delta drive distinct cardiac metabolic regulatory programs
      and identify PPARbeta/delta as a potential target for metabolic modulation
      therapy aimed at cardiac dysfunction caused by diabetes and ischemia.

PMID- 18037995
TI  - Tissue-type plasminogen activator promotes murine myofibroblast activation
      through LDL receptor-related protein 1-mediated integrin signaling.
AB  - The activation of interstitial fibroblasts to become alpha-SMA-positive
      myofibroblasts is an essential step in the evolution of chronic kidney fibrosis,
      as myofibroblasts are responsible for the production and deposition of the ECM
      components that are a hallmark of the disease. Here we describe a signaling
      pathway that leads to this activation. Tissue-type plasminogen activator (tPA)
      promoted TGF-beta1-mediated alpha-SMA and type I collagen expression in rat
      kidney interstitial fibroblasts. This fibrogenic effect was independent of its
      protease activity but required its membrane receptor, the LDL receptor-related
      protein 1 (LRP-1). In rat kidney fibroblasts, tPA induced rapid LRP-1 tyrosine
      phosphorylation and enhanced beta1 integrin recruitment by facilitating the LRP
      1/beta1 integrin complex formation. Blockade or knockdown of beta1 integrin
      abolished type I collagen and alpha-SMA expression. Furthermore, inhibition of
      the integrin-linked kinase (ILK), a downstream effector of beta1 integrin, or
      disruption of beta1 integrin/ILK engagement, abrogated the tPA action, whereas
      ectopic expression of ILK mimicked tPA in promoting myofibroblast activation. In
      murine renal interstitium after obstructive injury, tPA and alpha-SMA colocalized
      with LRP-1, and tPA deficiency reduced LRP-1/beta1 integrin interaction and
      myofibroblast activation. These findings show that tPA induces LRP-1 tyrosine
      phosphorylation, which in turn facilitates the LRP-1-mediated recruitment of
      beta1 integrin and downstream ILK signaling, thereby leading to myofibroblast
      activation. This study implicates tPA as a fibrogenic cytokine that promotes the
      progression of kidney fibrosis.

PMID- 18037996
TI  - Bile salt-dependent lipase interacts with platelet CXCR4 and modulates thrombus
      formation in mice and humans.
AB  - Bile salt-dependent lipase (BSDL) is an enzyme involved in the duodenal
      hydrolysis and absorption of cholesteryl esters. Although some BSDL is
      transported to blood, the role of circulating BSDL is unknown. Here, we
      demonstrate that BSDL is stored in platelets and released upon platelet
      activation. Because BSDL contains a region that is structurally homologous to the
      V3 loop of HIV-1, which binds to CXC chemokine receptor 4 (CXCR4), we
      hypothesized that BSDL might bind to CXCR4 present on platelets. In human
      platelets in vitro, both BSDL and a peptide corresponding to its V3-like loop
      induced calcium mobilization and enhanced thrombin-mediated platelet aggregation,
      spreading, and activated alpha(IIb)beta(3) levels. These effects were abolished
      by CXCR4 inhibition. BSDL also increased the production of prostacyclin by human
      endothelial cells. In a mouse thrombosis model, BSDL accumulated at sites of
      vessel wall injury. When CXCR4 was antagonized, the accumulation of BSDL was
      inhibited and thrombus size was reduced. In BSDL(-/-) mice, calcium mobilization
      in platelets and thrombus formation were attenuated and tail bleeding times were
      increased in comparison with those of wild-type mice. We conclude that BSDL plays
      a role in optimal platelet activation and thrombus formation by interacting with
      CXCR4 on platelets.

PMID- 18037999
TI  - What's new in muscle and peripheral nerve diseases?
AB  - It is likely that most neuromuscular diseases that are described in humans will
      have a counterpart in our companion animals. With the advent of molecular
      genetics and the completion of the canine and feline genomes, an ever expanding
      number of DNA-based tests should become available for the diagnosis of muscle and
      peripheral nerve diseases. Molecular testing procedures should enable us to
      continue to unravel the molecular basis of neuromuscular diseases for which the
      cause is still unknown. It is important that accurate clinical evaluations and
      diagnostic testing, including muscle and peripheral nerve biopsies, are performed
      in order to reach these goals. This review focuses on recently identified
      inherited neuromuscular diseases in companion animals.

PMID- 18037997
TI  - PKCtheta promotes c-Rel-driven mammary tumorigenesis in mice and humans by
      repressing estrogen receptor alpha synthesis.
AB  - The vast majority of primary human breast cancer tissues display aberrant nuclear
      NF-kappaB c-Rel expression. A causal role for c-Rel in mammary tumorigenesis has
      been demonstrated using a c-Rel transgenic mouse model; however, tumors developed
      with a long latency, suggesting a second event is needed to trigger
      tumorigenesis. Here we show that c-Rel activity in the mammary gland is repressed
      by estrogen receptor alpha (ERalpha) signaling, and we identify an epigenetic
      mechanism in breast cancer mediated by activation of what we believe is a novel
      PKCtheta-Akt pathway that leads to downregulation of ERalpha synthesis and
      derepression of c-Rel. ERalpha levels were lower in c-Rel-induced mammary tumors
      compared with normal mammary gland tissue. PKCtheta induced c-Rel activity and
      target gene expression and promoted growth of c-Rel- and c-RelxCK2alpha-driven
      mouse mammary tumor-derived cell lines. RNA expression levels of PKCtheta and c
      Rel target genes were inversely correlated with ERalpha levels in human breast
      cancer specimens. PKCtheta activated Akt, thereby inactivating forkhead box O
      protein 3a (FOXO3a) and leading to decreased synthesis of its target genes,
      ERalpha and p27(Kip1). Thus we have shown that activation of PKCtheta inhibits
      the FOXO3a/ERalpha/p27(Kip1) axis that normally maintains an epithelial cell
      phenotype and induces c-Rel target genes, thereby promoting proliferation,
      survival, and more invasive breast cancer.

PMID- 18038000
TI  - Dowel pinning for feline metacarpal and metatarsal fractures.
AB  - The goal of this retrospective study was to describe dowel pinning, and to
      compare the results of osteosynthesis and external coaptation of metacarpal and
      metatarsal fractures in cats. Evaluation of the medical records of 351 cats
      yielded 63 cats treated with dowel pinning, 35 cats treated with external
      coaptation and 14 cats treated with both methods within the same limb. All of the
      cats had been re-evaluated at an average of 2.8 years (six months - 15 years)
      postoperatively. Dowel pinning was superior to external coaptation when all
      fractured bones of a limb could be pinned. When internal fixation of multiple
      fractures was not feasible in all fractured bones due to comminution or fragments
      that were too short to pin, the outcome was not significantly different from
      cases treated with external coaptation alone. Malunion was seen in 16% of
      fractured bones in cats treated with external coaptation and occurred secondary
      to implant bending in 3% of fractured bones treated with dowel pinning. The
      latter refers to one operated cat, which had four metacarpal fractures in the
      same limb. Radiographs taken at re-evaluation showed implant migration within the
      medullary canal in two cats, although neither showed any signs of non-union or
      lameness. Non-union was seen in one operated cat, in which the fracture (MC IV)
      could not be completely reduced with a K-wire. Osteomyelitis did not occur. Dowel
      pinning is an easy, inexpensive and effective technique for repair of metacarpal
      and metatarsal fractures in cats.

PMID- 18038001
TI  - Stiffness of modified Type 1a linear external skeletal fixators.
AB  - Modifications of a Type 1a external skeletal fixator (ESF) frame were evaluated
      by alternately placing transfixation pins on opposite sides of the connecting rod
      (Type 1a-MOD) or by placing additional connecting rods on either of the two
      inside (Type 1a-INSIDE) or two outside (Type 1a-OUTSIDE) transfixation pins. The
      objective of this study was to evaluate the stiffness of these modifications in
      terms of axial compression (AC), cranial-caudal bending (CCB), and medial-lateral
      bending (MLB). We hypothesized that these designs would allow significant
      increase in unilateral frame stiffness, over Type 1a, without proportional
      increase in frame complexity or technical difficulty of application. All of the
      ESF frames were constructed using large IMEX SKtrade mark clamps, 3.2 mm threaded
      fixation pins, 9.5 mm carbon fibre connecting rods and Delrin rods as bone
      models. Nine, eight pin frames of each design were constructed, and subjected to
      repetitive non-destructive loading forces (AC, CCB, MLB) using a materials
      testing machine. Frame construct stiffness for each force (AC, CCB, MLB) was
      derived from load-deformation curve analysis and displayed in N/mm. Data revealed
      the 1a-MOD and 1a-OUTSIDE constructs had significantly increased stiffness in CCB
      and AC as compared to the Type 1a constructs while all of the modified constructs
      were significantly stiffer in MLB than the Type 1a constructs.

PMID- 18038002
TI  - Tibial segmental bone defect treated with bone plate and cage filled with either
      xenogeneic composite or autologous cortical bone graft. An experimental study in
      sheep.
AB  - Tibia segmental defect healing in sheep were clinically, radiographically and
      histologically evaluated. Twelve young sheep aged four to five months were
      divided into two groups, G1 and G2. A 3.5 cm long segmental defect was created in
      the right tibial diaphysis with maintenance of the periosteum. The bone defects
      in both groups were stabilized with a bone plate combined with a titanium cage.
      In G1 the cage was filled with pieces of autologous cortical bone graft. In G2 it
      was filled with a composite biomaterial which consisted of inorganic bovine bone,
      demineralized bovine bone, a pool of bovine bone morphogenetic proteins bound to
      absorbable ultra-thin powdered hydroxyapatiteand bone-derived denaturized
      collagen. Except for one G1 animal, all of them showed normal limb function 60
      days after surgery. Radiographic examination showed initial formation of
      periosteal callus in both groups at osteo-tomy sites, over the plate or cage 15
      days postoperatively. At 60 and 90 days callus remodeling occurred. Histological
      and morphometric analysis at 90 days after surgery showed that the quantity of
      implanted materials in G1 and G2 were similar, and the quantity of new bone
      formation was less (p = 0.0048) and more immature in G1 than G2, occupying 51 +/-
      3.46% and 62 +/- 6.26% of the cage space, respectively. These results suggest
      that the composite biomaterial tested was a good alternative to autologous
      cortical bone graft in this experimental ovine tibial defect. However, additional
      evaluation is warranted prior to its clinical usage.

PMID- 18038003
TI  - A mechanical evaluation of pre-tapped and self-tapped screws in small bones.
AB  - The purpose of this study was to compare the holding powers of 2.7 mm pre-tapped
      and self-tapped screws placed closely together and tightened in small bones.
      Pairs of metatarsals were collected from healthy, skeletally mature Greyhounds
      and part of a 2.7 mm dynamic compression plate was fixed to the dorsal surface of
      each bone using three 2.7 mm screws. Identical screws were used throughout but
      only one of each pair of bones had threads pre-cut using a tap prior to
      insertion. All of the screws were tightened before the constructs were mounted in
      a materials testing machine and the centrally placed screw was loaded
      incrementally until failure. Load-deformation curves were plotted and yield
      point, ultimate load to failure, stiffness and energy prior to yield point were
      measured. Mean values were recorded for each parameter and Student's T-test was
      used to test the null hypothesis that there is no difference in holding power
      between pre-tapped and self-tapped screws. Significant mechanical differences
      were not found between pre-tapped and self-tapped screws placed closely together
      and tightened into small bones. Self-tapped screws can be considered for use in
      small animal surgery even when multiple screws are to be placed closely together
      in relatively small pieces of bone.

PMID- 18038004
TI  - A morphometric study on the cross-sections of the scapular spine in dogs.
AB  - In cases of unstable scapular body fractures, the base of the scapular spine is
      one of the sites where there is adequate bone for the application of plate
      fixation in dogs. In this type of fixation, the amount of bone is an important
      factor with regard to the holding power of the screw from the biomechanical
      viewpoint. Therefore, the aim of this paper is to present the detailed
      quantitative features of the sectional area of the scapular spine in dogs. A
      total of 28 scapulas from 14 dogs were used, and each was divided into 10 equal
      slices The height of the scapular spine, depths of the supra-spinous and
      infraspinus fossae were measured from the scanned images with the aid of a
      computer program. The results showed that the depth of the supraspinous fossa was
      greater in the ventral half of the spine, while the depth of the infraspinous was
      greater in the dorsal half. The differences between the depths of the two fossae
      were noticeable in the ventral half of the scapular spine.

PMID- 18038005
TI  - Fixation of humeral intercondylar fractures using a lateral plate in 14 dogs
      supported by finite element analysis of repair.
AB  - Fourteen Spaniels that presented with an intercondylar fracture of the distal
      humerus were managed using a lateral plate and an additional pin in twelve cases.
      Fixation of the fracture was achieved using a plate applied laterally which
      incorporated the transcondylar lag screw in the most distal hole. Of the 14
      cases, two had poor results, one of which was a bilateral case, whilst the
      remaining 12 cases had good or very good results with only occasional stiffness
      or lameness. Finite element (FE) modelling of a distal humerus was generated, and
      loading of fracture repairs using a lateral plate and caudal plate was completed
      in a comparative study to determine which fixation method resisted micro-motion
      most effectively. Finite element analysis revealed that the lateral plate
      fixation provided significantly more resistance to micro movement at the fracture
      site that the caudal plate fixation, with 40% more micro-motion in the latter.

PMID- 18038006
TI  - Mechanoreceptors in the medial and lateral glenohumeral ligaments of the canine
      shoulder joint.
AB  - In order to have a better understanding of the role of ligaments in canine
      shoulder joint stability, the presence of mechanoreceptors in the medial (MGHL)
      and lateral (LGHL) glenohumeral ligaments was detected by means of a modified
      gold chloride stain. Three morphologically distinct mechanoreceptors were
      identified: Ruffini receptors (type I endings), Pacinian corpuscles (type II
      endings) and Golgi tendon organ-like receptors (type III endings). These
      receptors are mainly localized at each end of the ligaments and are prevalently
      in their glenoid portion. In particular, in the MGHL the highest density was at
      the cranial arm of the insertion into the scapula. The variety of
      mechanoreceptors in canine shoulder ligaments might indicate an afferent function
      in providing the CNS with joint proprioceptive information. Therefore, besides
      acting as passive mechanical stabilizers, the MGHL and the LGHL may serve as
      sensory structures, contributing actively to joint stability. Ligamentous
      injuries which occur in shoulders not only affect mechanical restraint but also
      alter the proprioceptive input to the CNS by means of disruption of the
      mechanoreceptors.

PMID- 18038007
TI  - Canine hip dysplasia radiographic screening. Prevalence of rotation of the pelvis
      along its length axis in 7,012 conventional hip extended radiographs.
AB  - The prevalence of rotation of the pelvis along its length axis was noted, as was
      the number of rotations towards the right or left hand side of the dog, on 7,012
      conventional hip extended radiographs, which were sent for official screening.
      29.8% of the radiographs showed a rotation the pelvis. The rotation was
      statistically more frequent towards the left hand side of the dog. The number of
      rejected radiographs for too important pelvis rotation was only 5.2%. The
      consequences of the pelvis rotation on the Norberg-Olsson angle, on the dorsal
      femoral head coverage, and in the aspect of cranial acetabular edge have to be
      taken into account when scoring the dog for hip dysplasia.

PMID- 18038008
TI  - Force plate gait analysis at the walk and trot in dogs with low-grade hindlimb
      lameness.
AB  - OBJECTIVE: To evaluate the accuracy of force plate gait analysis at the walk and
      trot in dogs with low-grade hindlimb lameness. MATERIAL AND METHODS: Nineteen
      healthy dogs and 41 dogs with low-grade unilateral hindlimb lameness due to
      stifle or hip joint problems were walked and trotted over a force plate. Peak
      vertical forces (PVF) were recorded, and a symmetry index (SI) was calculated
      from the PVF of the hindlimbs. 'Cut-off' values were determined from the SI of
      the normal dogs. These cut-off values were used to discriminate lame dogs from
      normal ones. Sensitivity and specificity were evaluated for measurements at walk
      and trot, and the Cohen's Kappa coefficient (k) was used to determine the
      agreement between clinical lameness and force plate measurements, and between
      force plate results at walk and trot. Receiver Operating Characteristics (ROC)
      curve were plotted for both gaits to evaluate accuracy. RESULTS: The sensitivity
      of the measurements at walk was 0.63, and specifity was 0.95. The sensitivity of
      the measurements at trot was 0.90, and specificity was 1.0. Moderate agreement
      was found between force plate measurements at walk and trot, and between clinical
      gait assessment and force plate measurements at walk. Good agreement was found
      between clinical gait assessment and measurements at trot. ROC analyses revealed
      the trot (94.7% [91.7%; 97.7%]) to be the more accurate test than the walk (85.0%
      [80.1%; 89.9%]). CONCLUSION: The trotting gait was more sensitive and accurate
      than the walking gait for the differentiation of dogs with a low-grade hindlimb
      lameness from normal ones using force plate gait analysis.

PMID- 18038009
TI  - Measurement of velocity with a kinematic system versus a photocell system in the
      collection of canine ground reaction forces.
AB  - Velocities obtained from a five photocell system were compared to velocities of
      nine anatomical points on a handler and canine subject as reported by a kinematic
      system over the same distance. There was not a statistically significant
      difference between the velocities of the markers on the dogs' occipital
      protuberance and interscapular region compared with the velocity as reported by
      the photocell system. The average velocities of the three markers on the forelimb
      of the dogs and three markers on the handler's leg and one on the sacrum had
      statistically different values than the photocell system. Given these results,
      photocell systems with the same configuration in this study can be trusted to
      report accurate trunk velocities of canine subjects during the collection of
      ground reaction forces.

PMID- 18038010
TI  - Rod-through-plate fixation of canine diaphyseal fractures.
AB  - Efficacy of the rod-through-plate fixation for fracture repair was evaluated in
      six clinical cases of canine long bone fractures. This fixation incorporates
      principles of intramedullary and extramedullary osteosynthesis for transverse and
      short oblique fractures of long tubular bones. The plate-through-rod device is
      comprised of one pair of curved rods, a connecting plate and two bone screws. The
      connecting plate has both a hole and a channel on each end. Curved rods have a
      long curved part and a straight part with a hole in it for screw fixation. All
      components are made up of medical stainless steel. Clinical and radiographical
      examinations were performed from week seven to18 months after the operation.
      Functional abnormalities were not observed at this period in five patients and
      all fractures were healed. In one patient screw stripping in the proximal
      fragment of the femur was detected radiologically and minimal implant dislocation
      was noted at seven weeks after the initial repair. The rod-through-plate fixation
      method gives strong fixation of bone fragments with minimal traumatization of
      soft tissue during the operation. The design of the rod-through-plate is intended
      to reduce pressure of the plate on the cortex in the area of the fracture,
      whereas the dynamic fixation provided by the intramedullary rods may allow
      micromotion, thus stimulating callus formation and avoiding implant-induced
      osteoporosis. CLINICAL RELEVANCE: The rod-through-plate fixator has a simple
      construction and its use expands the treatment possibilities for diaphyseal
      fractures of long bones.

PMID- 18038011
TI  - A comparison of outcomes following tibial plateau levelling osteotomy and cranial
      tibial wedge osteotomy procedures.
AB  - The objective of this study was to determine whether clinical outcomes were
      superior and complication rates were lower in dogs that had had a cranial
      cruciate ligament rupture treated by tibial plateau levelling osteotomy (TPLO),
      compared to those dogs that had been treated using the original cranial tibial
      wedge osteotomy (CTWO) procedure. Thirty-seven client-owned dogs with cranial
      cruciate ligament rupture were included in the study: 19 dogs underwent a TPLO
      procedure, and 18 dogs underwent a CTWO procedure. The study was retrospective,
      with the data being obtained from medical records and a review of radiographs.
      The long-term outcome was assessed by means of an owner questionnaire using a
      visual analogue scale. For the majority of factors that were reviewed, there was
      not a significant difference in outcome between the dogs that had a TPLO or those
      that had undergone a CTWO. All of the dogs showed a rapid return to weight
      bearing after surgery, and at the six week re-examination, the majority of the
      dogs did not have any pain on stifle palpation. They displayed a good stifle
      range of motion and significantly lower lameness scores than those prior to
      surgery. The complication rates did not differ between the procedures, however,
      within this small sample of dogs, complications following a CTWO were more likely
      to require revision surgery.

PMID- 18038012
TI  - Augmentation of the transverse acetabular ligament in canine caudoventral hip
      luxation.
AB  - Open surgical fixation was performed on four hip joints in three dogs who were
      suffering from caudoventral hip luxations for which closed reduction had
      previously failed. Stabilization of the joint was achieved with a ventral
      coxofemoral approach, which augmented the function of the transverse acetabular
      ligament using a sling implant through a bone tunnel (n = 1), a sling implant
      around two pelvic screws (n = 1), or an internal fixator plate (n = 2).
      Transverse acetabular ligament augmentation resulted in successful joint
      stabilization in all cases, and should be considered for the surgical reduction
      of caudoventral hip luxations in dogs. The use of an internal fixator plate,
      while preserving soft-tissue blood supply and resulting in minimal to no long
      term arthritic changes, may provide an optimal outcome.

PMID- 18038013
TI  - Radiographic and clinical features of carpal varus associated with chronic sprain
      of the lateral collateral ligament complex in 10 dogs.
AB  - Lameness associated with carpal varus deformity was recognised in 10 dogs, eight
      of which were Dobermann Pinschers. The dogs had a mean age of seven years and
      nine months. Carpal varus was usually bilateral with concurrent carpal
      hyperflexion and pronation. Carpal varus was present prior to the onset of
      lameness in four cases. With stress radiography the median angle of varus
      deviation in all carpi was 14.6 degrees , and an increase in the size of the
      ulnar /ulnar carpal bone joint space was seen in six of the seven dogs.
      Radiographic changes included: enthesophyte formation at the proximolateral
      aspect of metacarpal V, periarticular soft tissue swelling, especially lateral,
      bone proliferation at the carpometacarpal joint I and enthesophyte formation at
      metacarpophalangeal joint V. Four dogs were admitted for problems other than
      carpal varus and lameness was not treated. Five dogs were treated with
      nonsteroidal anti-inflammatory drugs, but lameness was not completely resolved
      and became exacerbated with exercise. One dog was successfully treated by
      pancarpal arthrodesis.

PMID- 18038014
TI  - A specific oblique radiography, and treatment, of a medial coronoid process
      fracture.
AB  - Acute traumatic fracture of the medial coronoid process is rarely reported and
      has previously only been described in three dogs to date. A three-year-old
      Schapendoes was presented for an acute non weight-bearing lameness. The
      definitive diagnosis of a medial coronoid process fracture was delicate and based
      on the disto-medial proximo-lateral oblique radiographic view (Di35M-PrLO). The
      surgical removal of the fragment was performed using a medial arthroscopic
      approach. The outcome was rapidly favourable. Lameness disappeared and the follow
      up radiographs three months later revealed minimal reactions of osteoarthrosis.

PMID- 18038015
TI  - Retroperitoneal hemangiosarcoma causing chronic hindlimb lameness in a dog.
AB  - The clinical, radiographic, ultrasonographic, computed tomographic, surgical and
      histopathological findings in a Boxer dog with retroperitoneal hemangiosarcoma
      are described in this study. A seven-year-old, male, castrated Boxer dog was
      referred for evaluation of chronic hindlimb lameness. The physical examination
      revealed muscle atrophy and sciatic nerve deficits. Radiography and
      ultrasonography revealed a caudodorsal abdominal mass. Computed tomography
      revealed that the mass involved the left margin of the L7 vertebra, lumbosacral
      canal, and lumbosacral plexus. At surgery, a large retroperitoneal haematoma was
      removed. Histopathology of amorphous tissue found near the haematoma was
      consistent with haemangiosarcoma. The owner declined any further treatment. Ten
      weeks after discharge, the dog was euthanatized due to collapse and haemo
      abdomen.

PMID- 18038017
TI  - New metabolic and endocrine approaches in pediatrics.

PMID- 18038016
TI  - Chronic peritoneal effusion secondary to partial caudal vena cava obstruction
      following traumatic pneumothorax in a dog.
AB  - A three-year old, female Boxer Dog was treated initially with thoracocentesis for
      a right-sided pneumothorax. The dog was re-evaluated after three weeks because of
      an enlargement of the abdomen. A positive venogram revealed a ventral
      displacement of the caudal vena cava between the diaphragm and the heart, with a
      severe reduction of the diameter of the vein. An exploratory thoracotomy showed a
      displaced accessory lung lobe with an adhesion to the parietal pleura. Inflation
      of this lung lobe created a dynamic obstruction of the caudal vena cava, which
      resulted in ascites. Surgery offered successful treatment.

PMID- 18038018
TI  - Glycemic control and insulin therapy in sepsis and critical illness.
AB  - OBJECTIVE: To review the literature about the pathophysiology of hyperglycemia
      and glycemic control in children and adults with sepsis and critical illness.
      SOURCES: Non-systematic survey of the medical literature using MEDLINE and terms
      hyperglycemia, glycemic control, intensive insulin therapy, sepsis and intensive
      care. Articles were selected according to their relevance based on the authors'
      opinion. SUMMARY OF THE FINDINGS: Hyperglycemia is frequent in critically ill
      children and it is associated with worsened outcome. In adults, there is no
      consensus on the efficacy and safety of glycemic control. We describe the
      possible mechanisms involved in glucose toxicity and the beneficial effects of
      glycemic control. Initial studies showed that use of insulin to achieve glycemic
      control reduced morbidity and mortality in adult intensive care; however, recent
      studies have failed to confirm these findings. Importantly, it is evident that
      glycemic control is associated with increased incidence of hypoglycemia. The
      efficacy of glycemic control has not yet been studied in critically ill children.
      CONCLUSION: Glycemic control is a novel therapeutic option in critical care.
      Conflicting evidence in adults means that before we apply this approach to
      pediatrics it will need to be assessed in clinical trial.

PMID- 18038019
TI  - Hemodynamic and metabolic effects of vasopressin infusion in children with shock.
AB  - OBJECTIVE: Vasopressin is a neuropeptide hormone which has been used clinically
      for more than 50 years and plays a major role in circulatory homeostasis and in
      the regulation of serum osmolality. Recent work has emphasized its role in the
      treatment of septic shock. This paper reviews the physiology of this neurohormone
      and the available evidence in favor of its use as a vasodilator for children in
      shock. SOURCES: MEDLINE, using the terms vasopressin, vasodilation, shock and
      septic shock, plus synonyms and related terms. Classic publications on the topic
      were also reviewed and selected depending on their relevance to the study
      objectives. SUMMARY OF THE FINDINGS: Vasopressin is synthesized in the
      neurohypophysis and released in response to a decrease in plasma volume or an
      increase in serum osmolality. The action of vasopressin is mediated by the
      activation of oxytocin receptors and of several G protein-coupled receptors,
      which are classified according to their location and intracellular transmission
      routes as V1 receptors (or V1b), V2 and V3 receptors (or V1b). The main role of
      vasopressin is to induce vasoconstriction. However, in certain organs, it can
      also induce selective vasodilation. Several clinical studies in adults and
      children have reported that the effects of vasopressin for the treatment of
      vasodilatory septic shock, due to a variety of causes, are both beneficial and
      safe. CONCLUSIONS: The evidence is restricted. Most studies are retrospective and
      include a small number of patients. Nevertheless, there is significant experience
      concerning the use of vasopressin in Pediatrics. Vasopressin has a beneficial
      clinical effect in children and can be indicated in the treatment of refractory
      vasodilatory shock, after adequate volume resuscitation and when high doses of
      other vasopressors are not effective.

PMID- 18038020
TI  - New options in insulin therapy.
AB  - OBJECTIVE: To review the new options in insulin therapy for controlling diabetes
      mellitus in children and adolescents. SOURCES: Articles indexed in PubMed were
      located using the search terms insulin analogs in children and adolescents and
      reviewed. Information was also obtained from American Diabetes Association and
      Sociedade Brasileira de Diabetes consensus documents. SUMMARY OF THE FINDINGS:
      Information is presented on new analogs of insulin and, for purposes of
      comparison, the other insulin modalities currently available are also reviewed,
      focusing on insulin therapies which attempt to approximate basal-bolus treatment
      strategies to physiology. With the objective of obtaining improved metabolic
      control, more and more children are being put on multiple daily injection regimes
      or using continuous subcutaneous insulin infusion. It is difficult to achieve
      optimum glycemic control in children due to the increased risk of hypoglycemia
      resulting from the great variability in dietary intake habits and in physical
      activity levels. With diabetes type 1, if rapid-acting analogs are given
      subcutaneously in bolus, they generally reduce hypoglycemia episodes and
      postprandial glycemia levels, compared with regular human insulin, while basal
      analogs tend to reduce particularly the number of episodes of nocturnal
      hypoglycemia. CONCLUSIONS: Although the benefits to individual metabolic and
      clinical outcomes appear modest, the majority of studies demonstrate benefits
      when insulin analogs are used in the treatment of diabetes type 1 or 2.

PMID- 18038021
TI  - Metabolic syndrome: identifying the risk factors.
AB  - OBJECTIVES: To discuss the metabolic syndrome and identify its risk factors,
      including in the pediatric age group. SOURCES: Indexed review articles. SUMMARY
      OF THE FINDINGS: The metabolic syndrome is characterized by insulin resistance
      and the presence of risk factors for cardiovascular diseases and diabetes
      mellitus type 2. Consensus has not yet been reached on its diagnostic criteria.
      This review presents diagnostic criteria defined by the American Heart
      Association (US National Cholesterol Education Program), the American Association
      of Clinical Endocrinologists, the World Health Organization and the International
      Diabetes Federation and discusses the possibilities of applying them to children.
      Pathophysiologic features of the syndrome are also covered, principally those
      related to the perinatal period and childhood. CONCLUSIONS: The metabolic
      syndrome is being diagnosed with ever greater frequency, principally during
      adolescence. Lifestyle changes, such as to diet and level of physical activity
      are fundamental to prevention. Treatment with medication and, in extreme cases,
      with surgery should also be considered, depending on severity and age.

PMID- 18038022
TI  - Challenges for our century: an environmentally healthy world is possible.

PMID- 18038023
TI  - [Health and environment in Brazil: development, territory, and social iniquity].
AB  - The present paper deals with the subject of socio-environmental injustice in
      Brazil as a consequence of the country's current development model in the context
      of globalization and from the perspective of social struggle. Over time the
      realization of the development ideology has introduced profound changes in the
      country's territory, with severe repercussions for population and ecosystem
      health that have only recently been included on the social agenda. Efforts to
      reconcile solutions to the social and environmental crises have converged in the
      concept of sustainable development, within new discourses in the field of
      collective health (and whose analysis provides the point of departure for this
      paper). Territory is explored as a useful tool for analyzing the relationship
      between health, environment, and development, revealing the paradox between
      Brazil's great natural and human potential and its poverty, reflecting
      environmental injustice and disregard for human rights. This expanded concept of
      territorial organization is important for understanding the context of
      modernization and the possibility for poor populations to enjoy a better life.

PMID- 18038032
TI  - [Political ecology, ecological economics, and public health: interfaces for the
      sustainability of development and health promotion].
AB  - This article proposes to focus contributions from political ecology and
      ecological economics to the field of collective health with a view towards
      integrating the discussions around health promotion, socio-environmental
      sustainability, and development. Ecological economics is a recent
      interdisciplinary field that combines economists and other professionals from the
      social, human, and life sciences. The field has developed new concepts and
      methodologies that seek to grasp the relationship between the economy and
      ecological and social processes such as social metabolism and metabolic profile,
      thereby interrelating economic, material, and energy flows and producing
      indicators and indexes for (un)sustainability. Meanwhile, political ecology
      approaches ecological issues and socio-environmental conflicts based on the
      economic and power dynamics characterizing modern societies. Collective health
      and the discussions on health promotion can expand our understanding of
      territory, communities, and the role of science and institutions based on the
      contributions of political ecology and ecological economics in analyzing
      development models and the distributive and socio-environmental conflicts
      generated by them.

PMID- 18038033
TI  - Environmental sustainability and human well-being indicators from the ecosystem
      perspective in the Middle Paraiba Region, Rio de Janeiro State, Brazil.
AB  - Population urbanization is a global trend, and socioeconomic activities in urban
      areas cause changes that affect the environment and human well-being beyond the
      specific territories, thus connecting urban to non-urban areas and creating city
      regions. This article's objective, from an ecosystem perspective, is to gather a
      set of information on municipalities (counties) belonging to the Middle Paraiba
      River Valley Region in the State of Rio de Janeiro, Brazil, in order to identify
      conditions and trends in environmental sustainability and well-being. The
      conceptual framework adopted here was that of the Millennium Ecosystem
      Assessment, identifying direct and indirect driving forces that affect human well
      being, with health as a component of the latter. We used a set of available
      public-domain data and information sources on the municipalities, grouped by
      socioeconomic and environmental conditions and the soundness of institutional
      structural well-being for sustainability. The indicators used here point to a
      process of degradation in the ecosystem services that has still not been
      prevented by the prevailing institutional structure, thus increasing constraints
      on well-being and the spread of socio-environmental impacts in the middle and
      long terms.

PMID- 18038034
TI  - Quantifying the impact of air pollution on the urban population of Brazil.
AB  - This study aimed to quantify air pollution impact on morbidity and mortality in
      the Brazilian urban population using locally generated impact factors.
      Concentration-response coefficients were used to estimate the number of
      hospitalizations and deaths attributable to air pollution in seven Brazilian
      cities. Poisson regression coefficients (beta) were obtained from time-series
      studies conducted in Brazil. The study included individuals 65 years old and over
      and children under five. More than 600 deaths a year from respiratory causes in
      the elderly and 47 in children were attributable to mean air pollution levels,
      corresponding to 4.9% and 5.5% of all deaths from respiratory causes in these age
      groups. More than 4,000 hospital admissions for respiratory conditions were also
      attributable to air pollution. These results quantitatively demonstrate the
      currently observed contribution of air pollution to mortality and
      hospitalizations in Brazilian cities. Such assessment is thought to help support
      the planning of surveillance and control activities for air pollution in these
      and similar areas.

PMID- 18038035
TI  - [Screening methodology application to evaluate cancer mortality in selected
      cities in the State of Minas Gerais, Brazil].
AB  - An epidemiological investigation was launched in several cities in southern Minas
      Gerais State, Brazil, considering the possibility of increased cancer incidence
      due to high exposure to natural radiation. First, the cancer mortality patterns
      were assessed to determine whether there was an increase in cancer deaths and to
      discuss the possible risk factors related to such an increase. The study proposed
      the use of a screening methodology based on standardized mortality ratio (SMR) in
      order to classify priority areas for future studies. Cities considered high
      priority for further investigation were: Andradas, for lung cancer in men (SMR =
      208 (106-310)) and liver cancer in women (SMR = 403 (104-701)); Pocos de Caldas,
      leukemia in men and women (SMR = 284 (156-412)) and SMR = 211 (111-312),
      respectively); Pouso Alegre, leukemia in men (SMR = 333 (127-540)) and
      hematological cancers in women (SMR = 257 (188-396)). Epidemiological studies are
      necessary to evaluate the role of radiation and other risk factors in these
      cancers and thus to support future preventive and control measures.

PMID- 18038036
TI  - [Integrated understanding for health surveillance in a forest environment: the
      case of the Araripe Plateau in Ceara State, Brazil].
AB  - Partial results from this study are presented with the objective of developing a
      health surveillance model for communities living on natural resources in the
      Araripe National Forest in Ceara State, Brazil. The research is justified
      primarily on the basis of this forest's importance for quality of life in
      Northeast Brazil and preservation of the country's forests in general. The study
      drew on a collective construction of integrated understanding on the subjectivity
      of social relations with the environment. Social and environmental health
      problems in the forest context have generally been overlooked by health policy.

PMID- 18038037
TI  - Health, environmental, and economic costs from the use of a stabilized
      diesel/ethanol mixture in the city of Sao Paulo, Brazil.
AB  - In Greater Metropolitan Sao Paulo, Brazil, fossil fuel combustion in the
      transportation system is a major cause of outdoor air pollution. Air quality
      improvement requires additional policies and technological upgrades in fuels and
      vehicle engines. The current study thus simulated the environmental and social
      impacts resulting from the use of a stabilized diesel/ethanol mixture in the bus
      and truck fleet in Greater Metropolitan Sao Paulo. The evaluation showed
      reductions in air pollutants, mainly PM10, which would help avert a number of
      disease events and deaths, as estimated through dose-response functions of
      epidemiological studies on respiratory and cardiovascular diseases. Valuation of
      the impacts using an environmental cost-benefit analysis considered operational
      installation, job generation, potential carbon credits, and health costs, with an
      overall positive balance of US$ 2.851 million. Adding the estimated qualitative
      benefits to the quantitative ones, the project's benefits far outweigh the
      measured costs. Greater Metropolitan Sao Paulo would benefit from any form of
      biodiesel use, producing environmental, health and socioeconomic gains, the three
      pillars of sustainability.

PMID- 18038038
TI  - [Association between air pollution and respiratory and cardiovascular diseases in
      Itabira, Minas Gerais State, Brazil].
AB  - The city of Itabira, Minas Gerais State, Brazil, is located in the Espinhaco
      Mountain Range, an area that features large-scale mechanized iron ore pit mines.
      The current study evaluates the acute effects of inhalable particulate matter
      (PM10) in terms of emergency room visits due to respiratory and cardiovascular
      diseases in Itabira. Generalized additive Poisson regression models were adopted,
      controlling for temperature, humidity, and both short and long-term seasonality.
      Increases of 10mg/m(3) in PM10 were associated with increases in respiratory
      emergency room visits of 4% (95%CI: 2.2-5.8), at lags 0 and 1 for children and
      adolescents younger than 13 years of age, and of 12% (95%CI: 8.5-15.5) on the
      three subsequent days for adolescents (13 to 19 years of age). For cardiovascular
      diseases, the effect was acute (4%; 95%CI: 0.8-8.5) and mainly for the 45 to 64
      age group. These results show that PM10 generated by open pit mining can lead to
      health problems in the exposed population.

PMID- 18038039
TI  - Decreased intelligence in children and exposure to fluoride and arsenic in
      drinking water.
AB  - Recent evidence suggests that fluoride (F) and arsenic (As) may adversely affect
      intelligence quotient (IQ) scores. We explore the association between exposure to
      F and As in drinking water and intelligence in children. Three rural communities
      in Mexico with contrasting levels of F and As in drinking water were studied:
      Moctezuma (F 0.8+/-1.4 mg/L; As 5.8+/-1.3 microg/L); Salitral (F 5.3+/-0.9 mg/L;
      As 169+/-0.9 microg/L) and 5 de Febrero (F 9.4+/-0.9 mg/L; As 194+/-1.3
      microg/L). The final study sample consisted of 132 children from 6 to 10 years
      old. After controlling for confounders, an inverse association was observed
      between F in urine and Performance, Verbal, and Full IQ scores (beta values = 
      13, -15.6, -16.9, respectively). Similar results were observed for F in drinking
      water (beta values = -6.7, -11.2, -10.2, respectively) and As in drinking water
      (beta values= -4.30, -6.40, -6.15, respectively). The p-values for all cases were
      < 0.001. A significant association was observed between As in urine and Full IQ
      scores (beta = -5.72, p = 0.003). These data suggest that children exposed to
      either F or As have increased risks of reduced IQ scores.

PMID- 18038040
TI  - [Air pollution and low birth weight in the city of Rio de Janeiro, Brazil, 2002].
AB  - The objective of this study was to evaluate the effect of air pollution on low
      birth weight in full term singleton newborns in the city of Rio de Janeiro,
      Brazil. The study adopted a cross-sectional design based on the year 2002. Data
      on live births were obtained from the Live Birth Information System of the
      Brazilian Ministry of Health. Low birth weight was defined as less than 2,500 g.
      Maternal exposure to air pollution was defined as the mean for a given pollutant
      over each trimester of pregnancy and was assessed taking birth date into account.
      Adjusted odds ratios (OR) were estimated for each potential risk factor. For
      PM(10), CO, and NO(2), no significant increases were detected. For SO(2), the OR
      of the fourth interquartile range of exposure in the third trimester of pregnancy
      was 1.149 (95%CI: 1.016-1.301). For O(3), the estimated OR was 0.830 (95%CI:
      0.750-0.987). When exposure variable was regarded as a continuous measure, the OR
      for PM(10), CO, and SO2 in the third trimester were not statistically significant
      and were 1.089, 2.223, and 1.259, respectively.

PMID- 18038041
TI  - ["Get it while you can!" attitude: late industrialization and implications for
      work, environment, and health in Ceara State, Brazil].
AB  - The present study focuses on the characteristics of late industrialization in a
      city in Ceara State (in the semiarid region of Northeast Brazil) and its
      implications for work, environment, and health in the context of industrial
      mobility and advanced capitalism. Using direct observation of work processes,
      interviews (with production managers, company presidents, workers, local
      authorities, and community leaders), institutional visits and secondary data
      analysis, eight recently built factories that manufacture chemicals, shoes,
      electric appliances, clothing, mechanical parts, and packaging were analyzed as
      to relocation, technology, organization, work relations, worker profile,
      environmental and occupational risks, and the impact of these factors on health
      and regulatory mechanisms. The lack of adequate criteria for attracting and
      accepting new investments, leading to a "get it while you can" attitude, the poor
      quality of jobs and environmental conditions, and the scale of new changes and
      risks in the area, like the difficulties of the public sector and society in
      dealing with these challenges, raise the issue of sustainability in the current
      development processes.

PMID- 18038042
TI  - [Health, environment, and pesticide use in a farming area in Rio de Janeiro
      State, Brazil].
AB  - Pesticide use in agriculture is a nationwide phenomenon in Brazil, and the
      problem is proportional to this vast country. The widespread and growing use of
      pesticides for crops and cattle-raising, among other applications, has caused a
      number of environmental changes and problems, both by contaminating the
      communities of living beings that comprise the environment and by accumulating in
      the biotic and abiotic segments of ecosystems (biota, water, air, soil, sediments
      etc.). Pesticides also cause a number of diseases and health problems in human
      populations. The current article discusses several pesticide-related implications
      for human health and the environment in the mountainous region of the State of
      Rio de Janeiro, an important farming center. The article presents the results of
      research in the area, identifying possible determinants of the current situation
      and some of the main challenges for dealing with the problem.

PMID- 18038043
TI  - Correlation between blood mercury levels in mothers and newborns in Itaituba,
      Para State, Brazil.
AB  - This study evaluated transplacental mercury transfer by measuring Hg in blood
      samples of mothers and newborns (umbilical cord) in hospitals in the municipality
      (county) of Itaituba, Para State, Brazil. Epidemiological and mercury exposure
      data were collected, besides clinical birth data. Mercury tests were performed by
      cold-vapor atomic absorption spectrophotometry. A total of 1,510 women and an
      equal number of their newborns participated in the study. Mean blood mercury was
      11.53 microg/L in mothers and 16.68 microg/L in newborns (umbilical cord). The
      highest Hg levels were in the 31-40-year maternal age group and their newborns,
      with 14.37 microg/L and 21.87 microg/L, respectively. However, in all age groups
      the mean mercury level was higher in newborns than in mothers. There was a strong
      positive correlation between Hg levels in newborns and mothers (r = 0.8019; p =
      0.000), with a significant linear regression model (r = 0.5283; p = 0.000). The
      results highlight the importance of monitoring pregnant women exposed to mercury
      as part of public health surveillance.

PMID- 18038044
TI  - Air pollution and respiratory diseases in the Municipality of Vitoria, Espirito
      Santo State, Brazil.
AB  - In Brazil, increasing air pollution in urban areas has led to a rise in
      respiratory diseases among children and the elderly and has also been the main
      cause of hospital admissions. This study aims to evaluate the air pollution
      levels in Vitoria, capital of Espirito Santo State, Brazil, in comparison to
      Brazilian legislation and recent World Health Organization (WHO) guidelines,
      analyzing the spatial distribution of asthma cases treated at local outpatient
      services. A descriptive epidemiological study was performed with daily records on
      air pollution and outpatient treatment for respiratory diseases from 2001 to
      2003, for children under 6 years of age. A geographic information system (GIS)
      was used to identify asthma distribution in the municipality. Air pollution
      levels were relatively low when compared to the Brazilian legislation and WHO
      guidelines. Only mean PM10 and NO2 exceeded the annual quality standard. The
      three highest asthma outpatient treatment rates were observed in the districts of
      Sao Jose, Jabou, and Morro do Quadro.

PMID- 18038045
TI  - [Household solid waste bagging and collection and their health implications for
      children living in outlying urban settlements in Salvador, Bahia State, Brazil].
AB  - This paper presents a study on the bagging and collection of household solid
      waste and the health implications for children. The research was conducted in
      nine human settlements on the outskirts of Salvador, Bahia State, Brazil.
      Intestinal nematode infection, predominantly involving Ascaris lumbricoides,
      Trichuris trichiura, and hookworms, was used as an epidemiological indicator in
      1,893 children from 5 to 14 years of age. The study also included diarrhea
      incidence and nutritional status as shown by anthropometric indicators in 1,204
      children less than 5 years of age. There was a higher prevalence of the three
      nematodes in children living in households without proper bagging/isolation and
      collection of household solid waste as compared to those in areas with regular
      garbage collection and adequate isolation of solid waste. The differences were
      statistically significant when other socioeconomic, cultural, demographic, and
      environmental risks factors were considered in the analysis. Similar results were
      also observed for epidemiological indicators, diarrhea incidence, and nutritional
      status.

PMID- 18038047
TI  - Poverty and development.

PMID- 18038048
TI  - The Safe Motherhood Initiative and beyond.

PMID- 18038049
TI  - Opening data to the world: why health numbers matter.

PMID- 18038050
TI  - Defeating dengue: a difficult task ahead.

PMID- 18038051
TI  - South African study highlights importance of research involving children.

PMID- 18038052
TI  - Saving mother's lives in rural Indonesia.

PMID- 18038053
TI  - The Global Fund expands its role. Interview by the Bulletin.

PMID- 18038054
TI  - Recent news from WHO.

PMID- 18038056
TI  - Delivery settings and caesarean section rates in China.
AB  - OBJECTIVE: To quantify the influence of increasing use of health-care services on
      rising rates of caesarean section in China. METHODS: We used data from a
      population-based survey conducted by the United Nations Population Fund during
      September 2003 in 30 selected counties in three regions of China. The study
      sample (derived from birth history schedule) consisted of 3803 births to mothers
      aged less than 40 years between 1993 and 2002. Multiple logistic regression
      models were used to estimate the effect of health-care factors on the odds of a
      caesarean section, controlling for time and selected variables. FINDINGS:
      Institutional births increased from 53.5% in 1993-1994 to 82.2% in 2001-2002,
      while the corresponding increase in births by caesarean section was from 8.9% to
      24.8%, respectively. Decomposition analysis showed that 69% of the increase in
      rates of caesarean section was driven by the increase in births within
      institutions. The adjusted odds of a caesarean section were 4.6 times (95%
      confidence interval, CI: 3.4-11.8) higher for recent births. The adjusted odds
      were also significantly higher for mothers who had at least one antenatal
      ultrasound test. Rates of caesarean section in secondary-level facilities
      markedly increased over the last decade to the same levels as in major hospitals
      (P < 0.001). CONCLUSION: The upsurge in rates of births by caesarean section in
      this population cannot be fully explained by increases in institutional births
      alone, but is likely to be driven by medical practice within secondary-level
      hospitals and women's demand for the procedure.

PMID- 18038055
TI  - Huge poor-rich inequalities in maternity care: an international comparative study
      of maternity and child care in developing countries.
AB  - OBJECTIVE: Progress towards the Millennium Development Goals for maternal health
      has been slow, and accelerated progress in scaling up professional delivery care
      is needed. This paper describes poor-rich inequalities in the use of maternity
      care and seeks to understand these inequalities through comparisons with other
      types of health care. METHODS: Demographic and Health Survey (DHS) data from 45
      developing countries were used to describe poor-rich inequalities by wealth
      quintiles in maternity care (professional delivery care and antenatal care), full
      childhood immunization coverage and medical treatment for diarrhoea and acute
      respiratory infections (ARI). FINDINGS: Poor-rich inequalities in maternity care
      in general, and professional delivery care in particular, are much greater than
      those in immunization coverage or treatment for childhood illnesses. Public
      sector inequalities make up a major part of the poor-rich inequalities in
      professional delivery attendance. Even delivery care provided by nurses and
      midwives favours the rich in most countries. Although poor-rich inequalities
      within both rural and urban areas are large, most births without professional
      delivery care occur among the rural poor. CONCLUSION: Poor-rich inequalities in
      professional delivery care are much larger than those in the other forms of care.
      Reducing poor-rich inequalities in professional delivery care is essential to
      achieving the MDGs for maternal health. The greatest improvements in professional
      delivery care can be made by increasing coverage among the rural poor. Problems
      with availability, accessibility and affordability, as well as the nature of the
      services and demand factors, appear to contribute to the larger poor-rich
      inequalities in delivery care. A concerted effort of equity-oriented policy and
      research is needed to address the huge poor-rich inequalities in maternity care.

PMID- 18038057
TI  - Magnesium sulfate is not used for pre-eclampsia and eclampsia in Mexico and
      Thailand as much as it should be.
AB  - OBJECTIVE: In the past ten years effective treatments for pre-eclampsia and
      eclampsia have been evaluated and identified following large trials and
      systematic reviews. We investigated the extent of those effective interventions
      implementation. METHODS: Descriptive analysis of data collected as part of a
      cluster randomized trial. The trial was assigned the International Standardised
      Randomized Controlled Trial Number ISRCTN 14055385. Hospitals with more than 1000
      deliveries per year not directly associated with an academic institution in
      Mexico City municipal area in Mexico (n = 22) and the north-east region of
      Thailand (n = 18) were included. All women delivering at the participating
      hospitals at two time periods in 2000 and 2002 contributed data on practice
      rates. The use of magnesium sulfate for pre-eclampsia and eclampsia were the
      outcomes. FINDINGS: Eight out of 22 hospitals in Mexico (range 0.8% to 8.5%) and
      all 18 hospitals in Thailand (range 18.6% to 63.6%) used magnesium sulfate for
      women with pre-eclampsia. In Mexico, 11 of 22 hospitals used magnesium sulfate
      for eclampsia (range 9.1% to 60.0%). In Thailand, all 17 hospitals having
      eclampsia cases used magnesium sulfate (range 25% to 100%). CONCLUSION: Despite
      compelling evidence, magnesium sulfate use is below desired levels. Clinical
      practices should be audited and implementation of this effective intervention
      should be taken up as a priority where universal implementation is not in place.

PMID- 18038058
TI  - Contraceptive injections by community health workers in Uganda: a nonrandomized
      community trial.
AB  - OBJECTIVE: To compare the safety and quality of contraceptive injections by
      community-based health workers with those of clinic-based nurses in a rural
      African setting. METHODS: A nonrandomized community trial tested provision of
      injectable Depo Provera (DMPA) by community reproductive health workers and
      compared it with routine DPMA provision at health units in Nakasongola District,
      Uganda. The primary outcome measures were safety, acceptability and continuation
      rates. FINDINGS: A total of 945 new DMPA users were recruited by community
      workers, clinic-based nurses and midwives. Researchers successfully followed 777
      (82% follow-up): 449 community worker clients and 328 clinic-based clients.
      Ninety-five percent of community-worker clients were "satisfied" or "highly
      satisfied" with services, and 85% reported receiving information on side-effects.
      There were no serious injection site problems in either group. Similarly, there
      was no significant difference between continuation to second injection (88% among
      clients of community-based workers, 85% among clinic-going clients), nor were
      there significant differences in other measures of safety, acceptability and
      quality. CONCLUSION: Community-based distribution (CBD) of injectable
      contraceptives is now routine in some countries in Asia and Latin America, but is
      practically unknown in Africa, where arguably the need for this practice is
      greatest. This research reinforces experience from other regions suggesting that
      well-trained community health workers can safely provide contraceptive
      injections.

PMID- 18038059
TI  - Did the strategy of skilled attendance at birth reach the poor in Indonesia?
AB  - OBJECTIVE: To assess whether the strategy of "a midwife in every village" in
      Indonesia achieved its aim of increasing professional delivery care for the
      poorest women. METHODS: Using pooled Demographic and Health Surveys (DHS) data
      from 1986-2002, we examined trends in the percentage of births attended by a
      health professional and deliveries via caesarean section. We tested for effects
      of the economic crisis of 1997, which had a negative impact on Indonesias health
      system. We used logistic regression, allowing for time-trend interactions with
      wealth quintile and urban/rural residence. FINDINGS: There was no change in rates
      of professional attendance or caesarean section before the programmes full
      implementation (1986-1991). After 1991, the greatest increases in professional
      attendance occurred among the poorest two quintiles -- 11% per year compared with
      6% per year for women in the middle quintile (P = 0.02). These patterns persisted
      after the economic crisis had ended. In contrast, most of the increase in rates
      of caesarean section occurred among women in the wealthiest quintile. Rates of
      caesarean deliveries remained at less than 1% for the poorest two-fifths of the
      population, but rose to 10% for the wealthiest fifth. CONCLUSION: The Indonesian
      village midwife programme dramatically reduced socioeconomic inequalities in
      professional attendance at birth, but the gap in access to potentially life
      saving emergency obstetric care widened. This underscores the importance of
      understanding the barriers to accessing emergency obstetric care and of the ways
      to overcome them, especially among the poor.

PMID- 18038060
TI  - Are skilled birth attendants really skilled? A measurement method, some
      disturbing results and a potential way forward.
AB  - OBJECTIVE: Delivery by a skilled birth attendant (SBA) serves as an indicator of
      progress towards reducing maternal mortality worldwide -- the fifth Millennium
      Development Goal. Though WHO tracks the proportion of women delivered by SBAs, we
      know little about their competence to manage common life-threatening obstetric
      complications. We assessed SBA competence in five high maternal mortality
      settings as a basis for initiating quality improvement. METHODS: The WHO
      Integrated Management of Pregnancy and Childbirth (IMPAC) guidelines served as
      our competency standard. Evaluation included a written knowledge test, partograph
      (used to record all observations of a woman in labour) case studies and
      assessment of procedures demonstrated on anatomical models at five skills
      stations. We tested a purposive sample of 166 SBAs in Benin, Ecuador, Jamaica and
      Rwanda (Phase I). These initial results were used to refine the instruments,
      which were then used to evaluate 1358 SBAs throughout Nicaragua (Phase II).
      FINDINGS: On average, Phase I participants were correct for 56% of the knowledge
      questions and 48% of the skills steps. Phase II participants were correct for 62%
      of the knowledge questions. Their average skills scores by area were: active
      management of the third stage of labour -- 46%; manual removal of placenta --
      52%; bimanual uterine compression -- 46%; immediate newborn care -- 71%; and
      neonatal resuscitation -- 55%. CONCLUSION: There is a wide gap between current
      evidence-based standards and provider competence to manage selected obstetric and
      neonatal complications. We discuss the significance of that gap, suggest
      approaches to close it and describe briefly current efforts to do so in Ecuador,
      Nicaragua and Niger.

PMID- 18038062
TI  - The Chilean infant mortality decline: improvement for whom? Socioeconomic and
      geographic inequalities in infant mortality, 1990-2005.
AB  - OBJECTIVE: To measure socioeconomic inequalities and differential risk in infant
      mortality on national and regional levels in Chile from 1990 to 2005, and propose
      new policy targets. METHODS: The study analysed Chilean vital events registries
      from 1990 to 2005 for infant mortality by maternal education, head of household
      occupational status, cause, age and location of death. Annual infant mortality
      rates and relative risk were calculated by maternal education and head of
      household occupational status for each cause and age of death. Socioeconomic
      inequalities were then mapped to 29 regional health services. FINDINGS:
      Reductions in the national infant mortality rate were driven by reductions among
      highly educated mothers, while recent stagnation in the national rate is caused
      by high levels of infant mortality among uneducated mothers. These vulnerable
      households are particularly prone to infant mortality risk due to infectious
      disease and trauma. We also identify clustering of high socioeconomic
      inequalities in infant mortality throughout the poorer north, indigenous south
      and densely populated metropolitan centre of Santiago. Finally, we report large
      inequities in vital statistics coverage, with infant deaths among vulnerable
      households much more likely to be inadequately defined than in the remaining
      population. CONCLUSION: These results indicate that the socioeconomically
      disadvantaged in Chile are at a significantly higher risk for infant mortality by
      infectious diseases and trauma during the first month of life. Efforts to reduce
      national infant mortality in Chile and other countries must involve policies that
      target child survival for at-risk populations for specific diseases, ages and
      locations.

PMID- 18038061
TI  - Identifying barriers and facilitators towards implementing guidelines to reduce
      caesarean section rates in Quebec.
AB  - OBJECTIVE: To investigate obstetricians perceptions of clinical practice
      guidelines targeting management of labour and vaginal birth after previous
      caesarean birth, and to identify the barriers to, facilitators of and
      obstetricians solutions for implementing these guidelines in practice. METHODS:
      This qualitative study was conducted in three hospitals in Montreal that
      represent around 10% of births in Quebec. Data was collected from 10 focus
      groups, followed by six semi-structured interviews. Two researchers jointly
      analysed the verbatim transcripts according to A manual for the use of focus
      groups. FINDINGS: The identified barriers to and facilitators of the
      implementation of guidelines can be classified into four categories: 1) the
      hospital level, including management and hospital policies; 2) the departmental
      level, including local policies, leadership, organizational factors, economic
      incentive, and availability of equipment and staff; 3) the health professionals
      motivations and attitudes, including medico-legal concerns, skill levels,
      acceptance of guidelines and strategies used to implement recommendations; and 4)
      patients motivations. CONCLUSION: Identifying the barriers to and facilitators of
      the adoption of recommendations is an important way to guide the development of
      efficient strategies. The findings of this study suggest that the adoption of
      guidelines may be improved if local health professionals perceptions are
      considered to make recommendations more acceptable and useful. Our findings also
      support the assumption that obstetricians seek to implement best practices, but
      require evidence tools and support to assess their practices and enhance their
      performance. In addition, peer review activities championed by opinion leaders
      have been identified by obstetricians as the most suitable strategy to improve
      the use of the guidelines in their practices.

PMID- 18038063
TI  - Global Fund-supported programmes contribution to international targets and the
      Millennium Development Goals: an initial analysis.
AB  - OBJECTIVE: The Global Fund to Fight AIDS, Tuberculosis and Malaria is one of the
      largest funders to fight these diseases. This paper discusses the programmatic
      contribution of Global Fund-supported programmes towards achieving international
      targets and Millennium Development Goals, using data from Global Fund grants.
      METHODOLOGY: Results until June 2006 of 333 grants supported by the Global Fund
      in 127 countries were aggregated and compared against international targets for
      HIV/AIDS, tuberculosis and malaria. Progress reports to the Global Fund
      secretariat were used as a basis to calculate results. Service delivery
      indicators for antiretrovirals (ARV) for HIV/AIDS, case detection under the DOTS
      strategy for tuberculosis (DOTS) and insecticide-treated nets (ITNs) for malaria
      prevention were selected to estimate programmatic contributions to international
      targets for the three diseases. Targets of Global Fund-supported programmes were
      projected based on proposals for Rounds 1 to 4 and compared to international
      targets for 2009. FINDINGS: Results for Global Fund-supported programmes total
      544,000 people on ARV, 1.4 million on DOTS and 11.3 million for ITNs by June
      2006. Global Fund-supported programmes contributed 18% of international ARV
      targets, 29% of DOTS targets and 9% of ITNs in sub-Saharan Africa by mid-2006.
      Existing Global Fund-supported programmes have agreed targets that are projected
      to account for 19% of the international target for ARV delivery expected for
      2009, 28% of the international target for DOTS and 84% of ITN targets in sub
      Saharan Africa. CONCLUSION: Global Fund-supported programmes have already
      contributed substantially to international targets by mid-2006, but there is a
      still significant gap. Considerably greater financial support is needed,
      particularly for HIV, in order to achieve international targets for 2009.

PMID- 18038064
TI  - A systematic review of inequalities in the use of maternal health care in
      developing countries: examining the scale of the problem and the importance of
      context.
AB  - Two decades after the Safe Motherhood campaigns 1987 launch in India, half a
      million women continue to die from pregnancy-related causes every year. Key
      health-care interventions can largely prevent these deaths, but their use is
      limited in developing countries, and is reported to vary between population
      groups. We reviewed the use of maternal health-care interventions in developing
      countries to assess the extent, strength and implications of evidence for
      variations according to women's place of residence and socioeconomic status.
      Studies with data on use of a skilled health worker at delivery, antenatal care
      in the first trimester of pregnancy and medical settings for delivery were
      assessed. We identified 30 eligible studies, 12 of which were of high or moderate
      quality, from 23 countries. Results of these studies showed wide variation in use
      of maternal health care. Methodological factors (e.g. inaccurate identification
      of population in need or range of potential confounders controlled for) played a
      part in this variation. Differences were also caused by factors related to health
      care users (e.g. age, education, medical insurance, clinical risk factors) or to
      supply of health care (e.g. clinic availability, distance to facility), or by an
      interaction between such factors (e.g. perceived quality of care). Variation was
      usually framed by contextual issues relating to funding and organization of
      health care or social and cultural issues. These findings emphasize the need to
      investigate and assess context-specific causes of varying use of maternal health
      care, if safe motherhood is to become a reality in developing countries.

PMID- 18038065
TI  - Addressing smoking cessation in tuberculosis control.

PMID- 18038066
TI  - Inter-agency agreement on mental health and psychosocial support in emergency
      settings.

PMID- 18038067
TI  - Bombarding people with questions: a reconsideration of survey ethics.

PMID- 18038068
TI  - Reducing the impact of climate change.

PMID- 18038069
TI  - Will increased awareness of the health impacts of climate change help in
      achieving international collective action?

PMID- 18038070
TI  - Indias last bastion of polio at "tipping point".

PMID- 18038071
TI  - Climate change and human health.

PMID- 18038073
TI  - Economic evaluation of hepatitis B vaccination in low-income countries: using
      cost-effectiveness affordability curves.
AB  - OBJECTIVE: We sought to describe a method that explicitly considers both a health
      care programmes cost-effectiveness and its affordability. For illustration, we
      apply the method to the programme to vaccinate infants against hepatitis B in the
      Gambia. METHODS: We synthesized selected data and developed a computer-based
      model from the societal and payer perspectives to evaluate the cost-effectiveness
      of routine infant vaccination against hepatitis B in the Gambia compared with no
      vaccination. The primary outcome measure was cost per averted disability-adjusted
      life year (DALY), which was expressed in 2002 US dollars. We used Monte Carlo
      methods for uncertainty analysis to examine the affordability of the programme
      from the payers perspective, and we derived an affordability curve and cost
      effectiveness affordability curves for the programme. FINDINGS: In the Gambia,
      vaccinating infants against hepatitis B is highly cost-effective. Compared with
      offering no intervention, the vaccination programme would cost US$ 28 per DALY
      averted from the societal perspective or US$ 47 per DALY averted from the payers
      perspective. The programme also has the potential to be affordable, starting at a
      relatively low budget of US$ 160,000 per year. Combining the two dimensions of
      the outcome measure, the probability that vaccinating infants would be both cost
      effective and affordable is 40% at an annual programme budget of US$ 182,000 (the
      estimated total programme cost from the payers perspective), given a threshold
      cost-effectiveness value of US$ 47 per DALY averted. CONCLUSION: In the face of
      uncertainties about both the health and economic consequences of a vaccine
      programme, as well as the availability and magnitude of resources needed to fund
      the programme, cost-effectiveness affordability curves can provide information to
      decision-makers about the probability that a programme will be both cost
      effective and affordable: these are distinct but equally relevant considerations
      in resource-poor settings.

PMID- 18038074
TI  - Routine offer of antenatal HIV testing ("opt-out" approach) to prevent mother-to
      child transmission of HIV in urban Zimbabwe.
AB  - OBJECTIVE: To assess the impact of routine antenatal HIV testing for preventing
      mother-to-child transmission of HIV (PMTCT) in urban Zimbabwe. METHODS: Community
      counsellors were trained in routine HIV testing policy using a specific training
      module from June 2005 through November 2005. Key outcomes during the first 6
      months of routine testing were compared with the prior 6-month "opt-in" period,
      and clients were interviewed. FINDINGS: Of the 4551 women presenting for
      antenatal care during the first 6 months of routine HIV testing, 4547 (99.9%)
      were tested for HIV compared with 3058 (65%) of 4700 women during the last 6
      months of the opt-in testing (P < 0.001), with a corresponding increase in the
      numbers of HIV-infected women identified antenatally (926 compared with 513, P <
      0.001). During routine testing, more HIV-infected women collected results
      compared to the opt-in testing (908 compared with 487, P < 0.001) resulting in a
      significant increase in deliveries by HIV-infected women (256 compared with 186,
      P = 0.001); more mother/infant pairs received antiretroviral prophylaxis (n =
      256) compared to the opt-in testing (n = 185); and more mother/infant pairs
      followed up at clinics (105 compared with 49, P = 0.002). Women were satisfied
      with counselling services and most (89%) stated that offering routine testing is
      helpful. HIV-infected women reported low levels of spousal abuse and other
      adverse social consequences. CONCLUSION: Routine antenatal HIV testing should be
      implemented at all sites in Zimbabwe to maximize the public health impact of
      PMTCT.

PMID- 18038075
TI  - A national survey of the impact of rapid scale-up of antiretroviral therapy on
      health-care workers in Malawi: effects on human resources and survival.
AB  - OBJECTIVE: To assess the human resources impact of Malawis rapidly growing
      antiretroviral therapy (ART) programme and balance this against the survival
      benefit of health-care workers who have accessed ART themselves. METHODS: We
      conducted a national cross-sectional survey of the human resource allocation in
      all public-sector health facilities providing ART in mid-2006. We also undertook
      a survival analysis of health-care workers who had accessed ART in public and
      private facilities by 30 June 2006, using data from the national ART monitoring
      and evaluation system. FINDINGS: By 30 June 2006, 59 581 patients had accessed
      ART from 95 public and 28 private facilities. The public sites provided ART
      services on 2.4 days per week on average, requiring 7% of the clinician
      workforce, 3% of the nursing workforce and 24% of the ward clerk workforce
      available at the facilities. We identified 1024 health-care workers in the
      national ART-patient cohort (2% of all ART patients). The probabilities for
      survival on ART at 6 months, 12 months and 18 months were 85%, 81% and 78%,
      respectively. An estimated 250 health-care workers lives were saved 12 months
      after ART initiation. Their combined work-time of more than 1000 staff-days per
      week was equivalent to the human resources required to provide ART at the
      national level. CONCLUSION: A large number of ART patients in Malawi are managed
      by a small proportion of the health-care workforce. Many health-care workers have
      accessed ART with good treatment outcomes. Currently, staffing required for ART
      balances against health-care workers lives saved through treatment, although this
      may change in the future.

PMID- 18038076
TI  - Mental health reform in the Russian Federation: an integrated approach to achieve
      social inclusion and recovery.
AB  - OBJECTIVE: To facilitate mental health reform in one Russian oblast (region)
      using systematic approaches to policy design and implementation. METHODS: The
      authors undertook a three-year action-research programme across three pilot
      sites, comprising a multifaceted set of interventions combining situation
      appraisal to inform planning, sustained policy dialogue at federal and regional
      levels to catalyse change, introduction of multidisciplinary and intersectoral
      working at all levels, skills-based training for professionals, and support for
      nongovernmental organizations (NGOs) to develop new care models. FINDINGS:
      Training programmes developed in this process have been adopted into routine
      curricula with measurable changes in staff skills. Approaches to care improved
      through multidisciplinary and multisectoral service delivery, with an increase in
      NGO activities, user involvement in care planning and delivery in all pilot
      sites. Hospital admissions at start and end of the study fell in two pilot sites,
      while the rate of readmissions in all three pilot sites by 2006 was below that
      for the region as a whole. Lessons learned have informed the development of
      regional and federal mental health policies. CONCLUSION: A multifaceted and
      comprehensive programme can be effective in overcoming organizational barriers to
      the introduction of evidence-based multisectoral interventions in one Russian
      region. This can help facilitate significant and sustainable changes in policy
      and reduce institutionalization.

PMID- 18038077
TI  - The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
      statement: guidelines for reporting observational studies.
AB  - Much biomedical research is observational. The reporting of such research is
      often inadequate, which hampers the assessment of its strengths and weaknesses
      and of a study's generalizability. The Strengthening the Reporting of
      Observational Studies in Epidemiology (STROBE) Initiative developed
      recommendations on what should be included in an accurate and complete report of
      an observational study. We defined the scope of the recommendations to cover
      three main study designs: cohort, case-control and cross-sectional studies. We
      convened a two-day workshop, in September 2004, with methodologists, researchers
      and journal editors to draft a checklist of items. This list was subsequently
      revised during several meetings of the coordinating group and in e-mail
      discussions with the larger group of STROBE contributors, taking into account
      empirical evidence and methodological considerations. The workshop and the
      subsequent iterative process of consultation and revision resulted in a checklist
      of 22 items (the STROBE Statement) that relate to the title, abstract,
      introduction, methods, results and discussion sections of articles. Eighteen
      items are common to all three study designs and four are specific for cohort,
      case-control, or cross-sectional studies. A detailed Explanation and Elaboration
      document is published separately and is freely available on the web sites of PLoS
      Medicine, Annals of Internal Medicine and Epidemiology. We hope that the STROBE
      Statement will contribute to improving the quality of reporting of observational
      studies.

PMID- 18038078
TI  - Intermittent preventive treatment of malaria during pregnancy in central
      Mozambique.
AB  - PROBLEM: New WHO strategies for control of malaria in pregnancy (MiP) recommend
      intermittent preventive treatment (IPTp), bednet use and improved case
      management. APPROACH: A pilot MiP programme in Mozambique was designed to
      determine requirements for scale-up. LOCAL SETTING: The Ministry of Health worked
      with a nongovernmental organization and an academic institution to establish and
      monitor a pilot programme in two impoverished malaria-endemic districts. RELEVANT
      CHANGES: Implementing the pilot programme required provision of additional
      sulfadoxine-pyrimethamine (SP), materials for directly observed SP
      administration, bednets and a modified antenatal card. National-level formulary
      restrictions on SP needed to be waived. The original protocol required
      modification because imprecision in estimation of gestational age led to missed
      SP doses. Multiple incompatibilities with other health initiatives (including
      programmes for control of syphilis, anaemia and HIV) were discovered and
      overcome. Key outputs and impacts were measured; 92.5% of 7911 women received at
      least 1 dose of SP, with the mean number of SP doses received being 2.2. At the
      second antenatal visit, 13.5% of women used bednets. In subgroups (1167 for
      laboratory analyses; 2600 births), SP use was significantly associated with
      higher haemoglobin levels (10.9 g/dL if 3 doses, 10.3 if none), less malaria
      parasitaemia (prevalence 7.5% if 3 doses, 39.3% if none), and fewer low-birth
      weight infants (7.3% if 3 doses, 12.5% if none). LESSONS LEARNED: National-level
      scale-up will require attention to staffing, supplies, bednet availability, drug
      policy, gestational-age estimation and harmonization of vertical initiatives.

PMID- 18038079
TI  - Offering integrated care for HIV/AIDS, diabetes and hypertension within chronic
      disease clinics in Cambodia.
AB  - PROBLEM: In Cambodia, care for people with HIV/AIDS (prevalence 1.9%) is
      expanding, but care for people with type II diabetes (prevalence 5-10%), arterial
      hypertension and other treatable chronic diseases remains very limited. APPROACH:
      We describe the experience and outcomes of offering integrated care for HIV/AIDS,
      diabetes and hypertension within the setting of chronic disease clinics. LOCAL
      SETTING: Chronic disease clinics were set up in the provincial referral hospitals
      of Siem Reap and Takeo, 2 provincial capitals in Cambodia. RELEVANT CHANGES: At
      24 months of care, 87.7% of all HIV/AIDS patients were alive and in active follow
      up. For diabetes patients, this proportion was 71%. Of the HIV/AIDS patients,
      9.3% had died and 3% were lost to follow-up, while for diabetes this included 3
      (0.1%) deaths and 28.9% lost to follow-up. Of all diabetes patients who stayed
      more than 3 months in the cohort, 90% were still in follow-up at 24 months.
      LESSONS LEARNED: Over the first three years, the chronic disease clinics have
      demonstrated the feasibility of integrating care for HIV/AIDS with non
      communicable chronic diseases in Cambodia. Adherence support strategies proved to
      be complementary, resulting in good outcomes. Services were well accepted by
      patients, and this has had a positive effect on HIV/AIDS-related stigma. This
      experience shows how care for HIV/AIDS patients can act as an impetus to tackle
      other common chronic diseases.

PMID- 18038080
TI  - Rose revisited: a "middle road" prevention strategy to reduce noncommunicable
      chronic disease risk.

PMID- 18038081
TI  - Pathways to homelessness among older people in Rio de Janeiro, Brazil.

PMID- 18038082
TI  - Shaping the world to illustrate inequalities in health.

PMID- 18038083
TI  - Malaria, mosquitoes and the legacy of Ronald Ross.

PMID- 18038084
TI  - [Brazilian response to tuberculosis: context, challenges and perspectives].

PMID- 18038085
TI  - [Evaluation of tuberculosis control strategies in Brazil. Foreword].

PMID- 18038086
TI  - [Two decades of research on tuberculosis in Brazil: state of the art of
      scientific publications].
AB  - The trends of scientific articles about tuberculosis in Brazil published between
      1986 and 2006 were analyzed. This analysis included Capes database-indexed
      dissertations and theses and papers indexed in Medline and SciELO. Papers
      containing the word "tuberculosis" and authors affiliated to Brazilian
      institutions were included in the assessment. The analysis showed initially case
      report and review publications, and later it shifted to original articles on
      science, technology and innovation. These changes may reflect the strengthening
      of scientific research activities and new attitudes regarding tuberculosis
      research objectives in academic institutions in recent years. Although many
      theses used qualitative methodology, few qualitative publications were found,
      possibly because of the quantitative orientation of many journals. Qualitative
      versus quantitative research and education versus research-oriented publications
      are discussed, together with public policies and strategies to include research
      as a tool to control diseases. The use of the same methodology is suggested to
      assess the trends in research on other neglected diseases.

PMID- 18038087
TI  - [Mortality trends due to tuberculosis in Brazil, 1980-2004].
AB  - OBJECTIVE: To analyze the current profile and trends of tuberculosis mortality in
      Brazil between 1980 and 2004. METHODS: Descriptive study of tuberculosis as
      underlying or associate cause of death based on secondary data from the Brazilian
      Mortality Information System. RESULTS: An irregular reduction in the number of
      tuberculosis deaths and mortality rates along the study period, from 5.8 in 1980
      to 2.3 per 100,000 inhabitants in 2004, was seen. An accelerated reduction in
      mortality trend was seen until 1985 mostly in the states of Rio de Janeiro and
      Sao Paulo. There was a trend towards mortality occurring in older ages. In 2004,
      4,981 tuberculosis cases were notified as underlying cause of death in Brazil but
      it would increase by 50% if tuberculosis as associate cause and tuberculosis
      sequelae as underlying cause of death were added. In 2004, the highest mortality
      rates were found in the states of Pernambuco (5.4) and Rio de Janeiro (5.0) and
      in state capitals such as Recife (7.7) and Belem (5.8). CONCLUSIONS: Given the
      well-known association between tuberculosis and Aids, the impact of AIDS epidemic
      indirectly reflects on the mortality trends of tuberculosis.

PMID- 18038088
TI  - [Tuberculosis incidence and cure rates, Brazil, 2000-2004].
AB  - OBJECTIVE: To describe the geographical distribution of tuberculosis incidence
      rates based on a set of epidemiological and operational indicators from
      information system database. METHODS: Data from the Sistema de Informacao de
      Agravos de Notificacao (Brazilian Information System for Tuberculosis
      Notification) were collected after removal of improper repeat records and record
      linkage. Tuberculosis incidence rates were estimated according to geographical
      unit, age group, sex, clinical manifestation and treatment schedule and
      standardized for population age group distribution based on 2000 Population
      Census. RESULTS: In 2004, in Brazil, tuberculosis incidence rate was 41 per
      100,000 inhabitants and 74,540 new cases were notified. Of these, 52.8% were
      pulmonary tuberculosis with positive bacilloscopy, 24.1% were under supervised
      treatment, 63.5% were from state capitals or metropolitan areas, and 54.9% were
      cured cases (complete treatment). After records with missing outcome data were
      excluded, cure rates were 72.4% for new cases, 47% for new HIV-positive cases,
      64.9% for relapses, 64.5% for transfers in/out, and 40% for returns after
      default. Cure rate for new cases under supervised treatment was 77.1%. A higher
      proportion of records with missing outcome information was seen in recent years.
      CONCLUSIONS: Different incidence rates and treatment outcomes were found in
      different Brazilian states. To reach the 85% cure goal for new cases and to
      increase cure in HIV-positive and defaults cases additional efforts are needed by
      the Brazilian National Tuberculosis Program, including scaling up the Directly
      Observed Therapy Strategy.

PMID- 18038089
TI  - [Multiresistant tuberculosis in Brazil: history and control].
AB  - The article aimed at assessing multidrug-resistant tuberculosis control in
      Brazil, based on the experiences of reference institutions, and the most relevant
      studies carried out to determine local and national resistance rates. Control
      measures and the current situation of treatment and diagnoses after the
      implementation of the national guidelines, which were revised in 2004, are
      considered. The first national survey on resistance to anti-tuberculosis drugs
      was performed in the middle of last decade. From its outcomes, a regimen to treat
      all cases of multidrug-resistant tuberculosis was validated and adopted.
      Government measures enabled the implementation of a surveillance system, whose
      outcomes are also commented.

PMID- 18038090
TI  - [Social representations of tuberculosis: stigma and prejudice].
AB  - Social representations of tuberculosis are analyzed at the turn of the 20th
      century, focusing on aspects associated to feelings and contradictory
      manifestations awakened by the disease. The romanticized pattern of experience of
      this disease was replaced by a more naturalistic vision, though the stigmas and
      prejudices are reinforced. To this day it is possible to detect some aspects
      about the way of perceiving tuberculosis, which marked its presence in the past.
      The persistence of the stigmatization of tuberculosis and of the people who
      suffer from it consists in a serious obstacle to the disease's control nowadays.

PMID- 18038091
TI  - [Retrospect of tuberculosis control in Brazil].
AB  - The aim of the study was to look back on the course of action involving measures
      of tuberculosis control in Brazil since the end of the 19th century, covering the
      history of social struggles and pointing out institutions and people that have
      dedicated themselves to looking for solutions to these issues. The Brazilian
      response to tuberculosis started in society with the Ligas Contra a Tuberculose
      (Leagues Against Tuberculosis), promoting scientific advances, such as the BCG
      vaccination, which begun in 1927. From the public power, the Inspetoria de
      Profilaxia da TB (TB Prophylaxis Inspection Service - 1920), the Servico Nacional
      de Tuberculose (National Service of Tuberculosis - 1940), and the Campanha
      Nacional Contra a Tuberculose (National Campaign Against Tuberculosis - 1946),
      coordinated national policies such as chemotherapy, beginning with the discovery
      of streptomycin in 1944. The emergence of bacterial resistance led to the
      development of several therapeutic schemes. The Scheme 1 (rifampycin, hydrazide
      and pyrazinamid), which was the main one in 1979 and is still used nowadays, had
      a great epidemiological effect. The WHO declared TB a public health emergency in
      1993. In response, Brazil developed some strategies; the first one was the Plano
      Emergencial para Controle da Tuberculose (Emergency Plan for Tuberculosis Control
      - 1994), prioritizing 230 municipalities. The current prospects are an effective
      municipalization of actions and their greater integration with the Programas de
      Agentes Comunitarios e Saude da Familia (Humanitarian Agents and Family Health
      Programs).

PMID- 18038092
TI  - [BCG vaccine against tuberculosis: its protective effect and vaccination
      policies].
AB  - OBJECTIVE: The BCG vaccine has been in use since 1921, but still arouses
      controversy and uncertainties. The objective was to analyze the protective effect
      of the BCG vaccine in its first and second doses and the accompanying vaccination
      policies. METHODS: A systematic review of the literature in both English and
      Spanish was carried out, covering the period 1948 to 2006, using the PubMed
      database. The main search terms used included BCG vaccine, BCG efficacy, BCG and
      tuberculosis. The studies were grouped by design, with the main results from the
      clinic tests, case-control studies and meta-analyses presented separately.
      RESULTS: The protective effect of the first dose of the BCG vaccine against
      tuberculosis in its miliary and meningeal forms is high. However, the results
      vary in relation to the pulmonary form of the disease, with some indicating zero
      effect and others levels of nearly 80%. Research is being carried out to develop
      new vaccines that could substitute the BCG or be used as a booster. CONCLUSIONS:
      There are evidences that the protective effect of the BCG vaccine does not
      increase with a second dose. In spite of its limitations and the expectation that
      a new tuberculosis vaccine will be developed in the future, the BCG vaccine
      remains an important tool in controlling the harmful effects of tuberculosis,
      particularly in countries with medium or high incidence levels of the disease.

PMID- 18038093
TI  - [Impact on tuberculosis incidence rates of removal of repeat notification
      records].
AB  - OBJECTIVE: To evaluate the impact on tuberculosis (TB) incidence rates of removal
      of improper duplicate records from the notification system. METHODS: Data from
      the Sistema de Informacao de Agravos de Notificacao (Brazilian Information System
      for Tuberculosis Notification) from 2000 to 2004 were analyzed. Repeat records
      were identified through probabilistic record linkage and classified into six
      mutually exclusive categories and then kept, combined or removed from database.
      RESULTS: Of all TB records, 73.7% had no duplicate, 18.9% were duplicate, 4.7%
      were triplicate, and 2.7% were quadruplicate or more. Of all repeat records,
      47.3% were classified as transfer in/out; 23.6% return after default, 16.4% true
      duplicates, 10% relapse, 2.5% inconclusive and 0.2% had missing data. These
      proportions were different in Brazilian states. Removal of improper duplicate
      records reduced TB incidence rate per 100.000 inhabitants by 6.1% in the year
      2000 (from 44 to 41.3), 8.3% in 2001 (from 44.5 to 40.8), 9.4% in 2002 (from 45.8
      to 41.5), 9.2% in 2003 (from 46.9 to 42.6) and 8.4% in 2004 (from 45.4 to 41.6).
      CONCLUSIONS: The study results indicate that the observed tuberculosis incidence
      rates represent estimates that would be closer to the actual rates than those
      obtained from the raw database at state and country level. The use of record
      linkage approach should be promoted for better quality of notification system
      data.

PMID- 18038094
TI  - [Tuberculosis surveillance and health information system in Brazil, 2001-2003].
AB  - OBJECTIVE: To assess the quality of tuberculosis surveillance in Brazil. METHODS:
      Local data from 2001 to 2003 were assessed according to the quality of detection
      and follow-up of the cases in the region, the quality of the information produced
      by the notification system, and the load of morbidity of tuberculosis. Cities
      were classified into four groups, according to tuberculosis epidemiologic stage
      and the quality of tuberculosis surveillance. RESULTS: In the study period, about
      8% of the Brazilian cities presented over 10% of the cases of tuberculosis
      notified by the health care services of another city. In about 950 cities, the
      frequency of patients with pulmonary tuberculosis undergoing sputum examination
      was lower than 90%. In the North region, Amazonas, Para and Amapa presented more
      cities classified in the groups of poor tuberculosis surveillance. In the
      Northeast, Pernambuco, Ceara and Bahia presented the poorest surveillance. The
      South and Midwest regions presented greater number of cities with better
      tuberculosis surveillance. CONCLUSIONS: One third of the Brazilian cities present
      poor tuberculosis surveillance. This picture is not homogeneous in Brazil, and
      the regions with highest tuberculosis incidence have a great number of cities
      with apparently insufficient control measures.

PMID- 18038095
TI  - [Brazilian response to tuberculosis control].
AB  - Tuberculosis remains a public health problem in Brazil. In 2003, controlling
      tuberculosis was highlighted as a priority among health public policies. The
      article reports the Brazilian response to this challenge, describing the main
      strategies of the National Control Plan for 2003 to 2006. Among its main results
      are: expansion of strategic coverage of the supervised treatment, increase in the
      percentage of cure, decrease in the number of patients' treatment dropout, and of
      the incidence rate.

PMID- 18038096
TI  - [Tuberculosis morbidity and effectiveness of the control program in Brazilian
      municipalities, 2001-2003].
AB  - OBJECTIVE: To analyze Brazilian municipalities according to morbidity and
      effectiveness of epidemiological inspection control of tuberculosis and AIDS.
      METHODS: Exploratory analysis of two non-hierarchical data clusters of
      epidemiological inspection data on tuberculosis and AIDS, and operational
      indicators of the Programa Nacional de Controle de Tuberculose (National
      Tuberculosis Control Program), from 2001 to 2003. The distribution was stratified
      in metropolitan areas and priority municipalities, according to the size of the
      population. The association between morbidity clusters and effectiveness was
      evaluated by the Chi-square test, with analysis of residues in order to identify
      significant associations. RESULTS: Out of the five morbidity clusters, the
      concerning epidemiological situation occurs in municipalities with high incidence
      of Aids, with high or low incidence of tuberculosis, prevailing in the Southeast
      and South of Brazil and larger cities. Out of the six program effectiveness
      clusters, moderate and average effectiveness are significantly associated to
      priority municipalities, in metropolitan areas with more than 80 thousand
      inhabitants. Clusters with average and poor effectiveness represent 10% of
      municipalities with elevated treatment drop out and low rates of cure. The "no
      data" cluster is associated with the very low incidence of tuberculosis and AIDS
      cluster. CONCLUSIONS: The findings reflect inadequacy of inspection concerning
      the epidemiological reality in Brazil: precarious social factors associated with
      tuberculosis and AIDS and insufficient effectiveness of the control program.

PMID- 18038097
TI  - [Tuberculosis and HIV infection in Brazil: magnitude of the problem and
      strategies for control].
AB  - The aim of the article was to propose, based on an analysis of the current
      scenario and of the interaction between tuberculosis and AIDS, strategies to
      minimize the epidemiological impact of one disease over the other in Brazil. The
      manner by which health policies aimed at controlling the HIV/AIDS epidemic is
      analyzed -- such as access to antiretroviral drugs and campaigns for the early
      detection of HIV infection and for encouraging adherence to treatment - and their
      impact on the achievement of goals related to controlling tuberculosis. The
      implementation of measures for preventing the onset of tuberculosis in HIV
      infected individuals, early detection of tuberculosis disease, and ensuring
      treatment adherence, is discussed. It is commented upon the role that Brazil may
      assume in the global effort to develop a therapeutic arsenal and the need for
      integrated work between the fields of tuberculosis and HIV/AIDS.

PMID- 18038098
TI  - [Strategies for tuberculosis control in Brazil: networking and civil society
      participation].
AB  - Although no significant changes in the tuberculosis indicators have been
      registered in Brazil in recent years, there is a clear shift in the political
      scenario regarding the manner this disease has been tackled, with the appearance
      of civil society standing out. Considerations about the conditions that
      contributed to its emergence are made, such as the origin, composition, actions,
      partners and perspectives on social mobilization. Due to initiatives for
      tuberculosis control on an international level and attempts to encourage social
      mobilization on state and municipal levels, the Brazilian federal government
      began to engage in a more consistent and coherent policy, also including civil
      society in its actions. In spite of being an actor acknowledged by the public
      power and considered strategic for the success of tuberculosis control actions,
      community participation requires incentives and constant support from other
      sectors.

PMID- 18038099
TI  - [Recent contribution of the World Health Organization to control childhood
      tuberculosis].
AB  - The article comments the pioneer and recent publication of the World Health
      Organization called "Guidance for National Tuberculosis Programmes on the
      Management of Childhood Tuberculosis in Children", aiming at spreading
      interesting aspects on the practice of health professionals. A parallel between
      Latin America and the African continent is established, concerning the co
      infection TB-HIV and childhood tuberculosis.

PMID- 18038100
TI  - [Data on tuberculosis in the state of Sao Paulo, Brazil].

PMID- 18038101
TI  - Connections: can the 20th century coronary heart disease epidemic reveal
      something about the 1918 influenza lethality?
AB  - This essay proposes that the ecologic association shown between the 20th century
      coronary heart disease epidemic and the 1918 influenza pandemic could shed light
      on the mechanism associated with the high lethality of the latter. It suggests
      that an autoimmune interference at the apoB-LDL interface could explain both
      hypercholesterolemia and inflammation (through interference with the cellular
      metabolism of arachidonic acid). Autoimmune inflammation, then, would explain the
      1950s-60s acute coronary events (coronary thrombosis upon influenza re-infection)
      and the respiratory failure seen among young adults in 1918. This hypothesis also
      argues that the lethality of the 1918 pandemic may have not depended so much on
      the 1918 virus as on an immune vulnerability to it, possibly resulting from an
      earlier priming of cohorts born around 1890 by the 1890 influenza pandemic virus.

PMID- 18038102
TI  - Purification, partial characterization and role in lipid transport to developing
      oocytes of a novel lipophorin from the cowpea weevil, Callosobruchus maculatus.
AB  - Lipid transport in arthropods is achieved by highly specialized lipoproteins,
      which resemble those described in vertebrate blood. Here we describe purification
      and characterization of the lipid-apolipoprotein complex, lipophorin (Lp), from
      adults and larvae of the cowpea weevil Callosobruchus maculatus. We also describe
      the Lp-mediated lipid transfer to developing oocytes. Lps were isolated from
      homogenates of C. maculatus larvae and adults by potassio bromide gradient and
      characterized with respect to physicochemical properties and lipid content. The
      weevil Lp (465 kDa) and larval Lp (585 kDa), with hydrated densities of 1.22 and
      1.14 g/mL, contained 34 and 56% lipids and 9 and 7% carbohydrates, respectively.
      In both Lps, mannose was the predominant monosaccharide detected by paper
      chromatography. SDS-PAGE revealed two apolipoproteins in each Lp with molecular
      masses of 225 kDa (apolipoprotein-I) and 79 kDa (apolipoprotein-II). The lipids
      were extracted and analyzed by thin-layer chromatography. The major phospholipids
      found were phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine
      in adult Lp, and phosphatidylcholine, phosphatidylethanolamine and sphingomyelin
      in larval Lp. Hydrocarbons, fatty acids and triacylglycerol were the major
      neutral lipids found in both Lps. Lps labeled in the protein moiety with
      radioactive iodine (125I-iodine) or in the lipid moiety with fluorescent lipids
      revealed direct evidence of endocytic uptake of Lps in live oocytes of C.
      maculatus.

PMID- 18038103
TI  - Application and implementation of the GINA asthma guidelines by specialist and
      primary care physicians: a longitudinal follow-up study on 264 children.
AB  - AIMS: To implement GINA guidelines and to assess their impact on the management
      of childhood asthma. METHODS: A working group of primary care physicians (PCPs)
      and specialists developed a GINA-based clinical pathway. We then monitored the
      impact on 385 children (aged 0-15 years) referred to the respiratory outpatients
      clinic at the University Children's Hospital, Brescia, Italy by 179 PCPs between
      September 2003 and July 2005. RESULTS: Mean follow-up for 264 children with
      complete datasets was 10 months. Guidelines were followed by 94.6% of the PCPs.
      98.6% of children learned to manage exacerbations. Half of the patients with
      persistent symptoms became intermittently symptomatic. Maintenance treatment was
      suspended in 47.2%, reduced in 27.6%, and increased in 4.9%. Asthma severity
      diminished (p<0.0001) and requirement for medication for exacerbations was
      significantly reduced (p<0.0001). CONCLUSIONS: Regular specialist visits, a
      website, and a written management plan shared by all those involved, led to
      clinical improvements as well as a reduction in, and more efficient use of,
      asthma medication.

PMID- 18038104
TI  - What are the needs of patients following discharge from hospital after an acute
      exacerbation of chronic obstructive pulmonary disease (COPD)?
AB  - AIM: To identify patient needs following discharge from hospital after an
      exacerbation of COPD. METHODS: Qualitative and semi-quantitative study using home
      based structured interviews and focus groups involving 25 COPD patients after
      hospital discharge. Interviews were performed seven days and three months post
      discharge. Quantitative data were analysed using descriptive statistics and were
      triangulated with the qualitative data from interviews and the focus groups.
      RESULTS: There were high levels of depression (64%) and anxiety (40%). Feelings
      of anxiety after discharge were associated with the fear of another "attack" and
      with uncertainties about social and medical care provision, especially the
      provision of oxygen. CONCLUSIONS: Interventions to reduce readmission for COPD
      exacerbations need to consider the psychosocial as well as the medical needs of
      patients. There appears to be a need for improved hospital discharge procedures
      and community follow-up - including the provision of pulmonary rehabilitation and
      encouragement of self-management strategies.

PMID- 18038105
TI  - Monitoring of exhaled nitric oxide in primary care.

PMID- 18038106
TI  - [Patient participation in medical care, taking rare retinal degenerations as
      examples].
AB  - Eight rare retinal degenerations were chosen to exemplify self-organisation and
      involvement of patient self-help groups in medical care. They were studied and
      supported in their development on the following levels: disease-specific groups
      (level 1), patient organisations (level 2), umbrella organisation (level 3).
      Databases of defined needs and concerns ("Themenspeicher") of disease-specific
      patient groups and of patient organisations with respect to care, research and
      patient networking were established. Priority concerns were implemented in the
      following areas: specialised medical care; quality assurance; quality management;
      expert panel with international dialogue of patients and physicians (including
      consensus statement on treatment recommendations); glossary internet portal;
      criteria for patient-oriented disease descriptions; structured documentation of
      patient experiences; patient management of health care records (paper bound and
      electronic health records). Apart from disease- specific approaches,
      interdisciplinary disease approaches were also applied, e.g. by contributing to
      the establishment of the German Alliance for Rare Diseases (ACHSE). This umbrella
      organisation has substantially improved chances for cooperation and patient
      advocacy. Patient participation was promoted by a federal regulation in 2004
      ("Patientenbeteiligungsverordnung"). The example of rare retinal degenerations
      demonstrates the advantage of strong patient and umbrella organisations. Further
      development of qualified self-help resources is required for patient
      participation in rare diseases.

PMID- 18038107
TI  - Anatomic variations of the pelvic floor nerves adjacent to the sacrospinous
      ligament: a female cadaver study.
AB  - Our objective was to document variations in the topography of pelvic floor nerves
      (PFN) and describe a nerve-free zone adjacent to the sacrospinous ligament (SSL).
      Pelvic floor dissections were performed on 15 female cadavers. The course of the
      PFN was described in relation to the ischial spine (IS) and the SSL. The pudendal
      nerve (PN) passed medial to the IS and posterior to the SSL at a mean distance of
      0.6 cm (SD = +/-0.4) in 80% of cadavers. In 40% of cadavers, an inferior rectal
      nerve (IRN) variant pierced the SSL at a distance of 1.9 cm (SD = +/-0.7) medial
      to the IS. The levator ani nerve (LAN), coursed over the superior surface of the
      SSL-coccygeus muscle complex at a mean distance of 2.5 cm (SD = +/-0.7) medial to
      the IS. Anatomic variations were found which challenge the classic description of
      PFN. A nerve-free zone is situated in the medial third of the SSL.

PMID- 18038108
TI  - Vitamin D-binding protein gene microsatellite polymorphism influences BMD and
      risk of fractures in men.
AB  - Here we report the results of a vitamin D-binding protein gene microsatellite
      polymorphism study in 170 men, comprising healthy male subjects and men with
      osteoporosis-related symptomatic vertebral fractures. We confirm the results of
      an earlier study in a different cohort, showing relationship between certain
      genotypes of (TAAAn)-Alu repeats and reduced BMD and vertebral fractures.
      INTRODUCTION: Vitamin D-binding protein (DBP) plays a critical role in the
      transport and metabolism of metabolites of vitamin D, including the key
      calciotropic hormone 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). METHODS: We
      have investigated intra-intronic variable tandem (TAAA)n-Alu repeat expansion in
      the DBP gene in 170 men, comprising healthy male subjects and men with idiopathic
      osteoporosis and low trauma fractures. RESULTS AND CONCLUSIONS: The predominant
      DBP-Alu genotype in the control subjects was 10/10 (frequency 0.421), whereas the
      frequency of this genotype in men with osteoporosis was 0.089. DBP-Alu alleles
      *10, *8 and *9, respectively, were the three commonest in both healthy subjects
      and men with osteoporosis. Allele *10 was associated with a lower risk of
      osteoporosis (OR 0.39, 95% CI 0.25-0.64; p < 0.0005), as was allele *11 (odds
      ratio 0.09, 95% CI 0.01-0.67; p < 0.007). Logistic regression gave similar
      results, showing that individuals with genotype 10/10 and 19-20 repeats
      (genotypes 9/10, 9/11, 10/10,) are protected from fracture or osteoporosis.
      Overall, there was a relationship between DBP Alu genotype and BMD, suggesting
      that DBP-Alu genotype may influence fracture risk. This effect may be mediated by
      changes in the circulating concentrations of DBP which influences free
      concentrations of vitamin D.

PMID- 18038109
TI  - Rate and circumstances of clinical vertebral fractures in older men.
AB  - We examined the rate of clinical vertebral fractures, and the circumstances
      associated with the fractures, in a cohort of 5,995 US older men. Fractures were
      more common in the most elderly men, and were usually associated with falls and
      other low-energy trauma. INTRODUCTION: Little is known about clinical vertebral
      fractures in older men. We postulated that clinical vertebral fractures occur
      with falls, affect men with osteoporosis, and are more common as age increases.
      METHODS: Five thousand nine hundred and ninety-five men aged > or =65 years were
      followed prospectively for an average of 4.7 years. Men with incident clinical
      vertebral fractures were compared to controls. RESULTS: One percent (n = 61)
      sustained incident clinical vertebral fractures (2.2/1,000 person-years). The
      rate of fracture rose with age (0.7% in men 65-69 years and 5% > or =85 years).
      Fractured men were more likely frail (8.2% vs. 2.2%), more often fell (36.1% vs.
      21%) and had lower total hip and lumbar spine BMD (all p values < or =0.002). In
      73.8% of cases fractures were precipitated by no known trauma or by low-energy
      trauma, including falls in 57.3% Fractures were thoracic in 33% and lumbar in
      56%. Men with an incident vertebral fracture were more likely to be osteoporotic
      (13% vs. 2%, p < 0.0001), but most men with incident fractures did not have
      osteoporosis. CONCLUSIONS: Incident clinical vertebral fractures were relatively
      common in older men and the rate increased after age 80 years. Fractures were
      usually associated with minimal trauma, most commonly a fall.

PMID- 18038110
TI  - Effects of verapamil and gadolinium on caffeine-induced contractures and calcium
      fluxes in frog slow skeletal muscle fibers.
AB  - In this work, we tested whether L-type Ca(2+ )channels are involved in the
      increase of caffeine-evoked tension in frog slow muscle fibers. Simultaneous net
      Ca(2+) fluxes and changes in muscle tension were measured in the presence of
      caffeine. Isometric tension was recorded by a mechanoelectrical transducer, and
      net fluxes of Ca(2+) were measured noninvasively using ion-selective vibrating
      microelectrodes. We show that the timing of changes in net fluxes and muscle
      tension coincided, suggesting interdependence of the two processes. The effects
      of Ca(2+)channel blockers (verapamil and gadolinium) were explored using 6 mM:
      caffeine; both significantly reduced the action of caffeine on tension and on
      calcium fluxes. Both caffeine-evoked Ca(2+) leak and muscle tension were reduced
      by 75% in the presence of 100 microM: GdCl(3), which also caused a 92% inhibition
      of net Ca(2+) fluxes in the steady-state condition. Application of 10 microM:
      verapamil to the bath led to 30% and 52% reductions in the Ca(2+)leak caused by
      the presence of caffeine for the peak and steady-state values of net Ca(2+)
      fluxes, respectively. Verapamil (10 microM): caused a 30% reduction in the
      maximum values of caffeine-evoked muscle tension. Gd(3+)was a more potent
      inhibitor than verapamil. In conclusion, L-type Ca(2+) channels appear to play
      the initial role of trigger in the rather complex mechanism of slow fiber
      contraction, the latter process being mediated by both positive Ca(2+)-induced
      Ca(2+ )release and negative (Ca(2+) removal from cytosol) feedback loops.

PMID- 18038112
TI  - Flory radius of polymers in a periodic field: an exact analytic theory.
AB  - We found an exact expression for the Flory radius R (F) of Gaussian polymers
      placed in an external periodic field. This solution is expressed in terms of the
      two parameters eta and a that describe the reduced strength of an external field
      and the period of the field to the polymer gyration radius ratio, respectively. R
      (F) is found to be a decaying function of eta for any values of a . Provided that
      the gyration radius is of the order of the period of an external field or less,
      the ground-state (GS) approximation of the exact result for R (F) is shown to
      give qualitatively incorrect results. In addition to the "ground-state"
      contribution, the exact solution for R (F) contains an additional term that is
      overlooked by the GS approximation. This term gives rise to the fact that R (F)
      as a function of eta exhibits power law behavior (rather than exponential decay
      obtained from the GS result) once eta exceeds the threshold value eta(con) .

PMID- 18038111
TI  - Vascular anatomical basis of clavicular non-union.
AB  - The middle third of the clavicle is commonly involved in any injury and account
      for 5-10% of all fractures in adults. Although non-unions are rare, their
      treatment has not been well defined yet. This report describes the arterial
      supply of the clavicle to clarify the pathological mechanism and the surgical
      procedure of non-unions. This study was based on delineation of the thoraco
      acromial and suprascapular arteries with colored latex on 17 specimens (ten
      cadavers). Observations were made after macroscopic dissection and maceration.
      The main blood supply to the middle third of the clavicle was the periosteal.
      This supply came from the two branches of the thoraco-acromial trunk that
      penetrated the pectoralis major muscle and the deltoid muscle. In 13 cases, these
      two periosteal branches were anastomosed between these two muscle attachments.
      Periosteal vascularization was always seen on the superior surface and the
      anterior border of the bone, but never on the inferior surface or the posterior
      border. The suprascapular artery contributed to supply the middle third of the
      clavicle by several periosteal branches and also by an independent branch. This
      branch was born proximally near the internal, middle thirds union and passed
      along the posterior face of the subclavius muscle and pierced the bone through
      the nutria foramina located near the external, middle thirds union. Nevertheless,
      intraosseous arteries were noted only in four cases. In these cases, they were
      never more than 2cm long. Our results showed that the periosteal blood supply
      located between the muscles insertions and the arterial supply from the
      suprascapular artery could be twice compromised in case of important displacement
      or severe fracture. If treatments of clavicular fractures or non-unions cannot
      preserve the periosteal blood supply, bone grafting should be indicated.

PMID- 18038113
TI  - Cloning and expression of the sucrose phosphorylase gene from Leuconostoc
      mesenteroides in Escherichia coli.
AB  - The gene encoding sucrose phosphorylase (742sp) in Leuconostoc mesenteroides NRRL
      B-742 was cloned and expressed in Escherichia coli. The nucleotide sequence of
      the transformed 742sp comprised an ORF of 1,458 bp giving a protein with
      calculated molecular mass of 55.3 kDa. 742SPase contains a C-terminal amino acid
      sequence that is significantly different from those of other Leu. mesenteroides
      SPases. The purified 742SPase had a specific activity of 1.8 U/mg with a K (m) of
      3 mM with sucrose as a substrate; optimum activity was at 37 degrees C and pH
      6.7. The purified 742SPase transferred the glucosyl moiety of sucrose to cytosine
      monophosphate (CMP).

PMID- 18038115
TI  - Acute phase proteins and systolic dysfunction in subjects with acute myocardial
      infarction.
AB  - AIM: To investigate correlations between plasmatic concentrations of acute phase
      proteins (APPs) and left ventricular systolic function during the early phase of
      acute myocardial infarction. METHODS: Plasmatic concentrations of alpha-1-anti
      trypsin (A1AT), alpha 1 glyco-protein (A1GP), haptoglobin (HG), caeruloplasmin
      (CP) and C-reactive protein (CRP) were evaluated in 123 patients with ST
      elevation acute myocardial infarction (STEMI) within 12 h after onset of chest
      pain. Systolic function was assessed with bi-dimensional echography and incidence
      of in-hospital adverse events was compared to APPs levels. RESULTS: A1AT, A1GP,
      HG and CP showed a statistically significant correlation with admission CRP
      concentrations (P < 0.001). Left ventricular ejection fraction inversely
      correlated with plasmatic concentrations of A1GP, A1AT, CP and HG. Incidence of
      acute heart failure correlated with values of APPs and, in a stepwise analysis,
      CP values were the most significant markers of acute heart failure. CONCLUSIONS:
      Systolic dysfunction in STEMI patients seems to be associated with an
      inflammatory response featured by a rise in plasmatic concentration of APPs;
      increase in APPs concentrations seems to own a short-term prognostic relevance.

PMID- 18038116
TI  - A structural perspective on mechanism and function of the cytochrome bc (1)
      complex.
AB  - The cytochrome bc (1) complex is a fundamental component of the energy conversion
      machinery of respiratory and photosynthetic electron transfer chains. The multi
      subunit membrane protein complex couples electron transfer from hydroquinone to
      cytochrome c to the translocation of protons across the membrane, thereby
      substantially contributing to the proton motive force that is used for ATP
      synthesis. Considerable progress has been made with structural and functional
      studies towards complete elucidation of the Q cycle mechanism, which was
      originally proposed by Mitchell 30 years ago. Yet, open questions regarding key
      steps of the mechanism still remain. The role of the complex as a major source of
      reactive oxygen species and its implication in pathophysiological conditions has
      recently gained interest.

PMID- 18038114
TI  - PvALF and FUS3 activate expression from the phaseolin promoter by different
      mechanisms.
AB  - Transcription from the phaseolin (phas) promoter requires two major events:
      chromatin remodeling, mediated by PvALF, a B3 domain factor, and activation by an
      ABA-induced signal transduction cascade. Expression from phas is normally seed
      specific, but high levels of expression in leaves can be obtained by ectopic
      expression of PvALF. Here, the system was used to compare the ability of PvALF
      and Arabidopsis FUS3, another B3 domain transcription factor that lacks the N
      terminal activation and B1 domain present in PvALF, to activate phas expression
      in vegetative tissues. When compared to PvALF-mediated phas activation in the
      presence of ABA, a delay in phas activation was observed in the presence of both
      FUS3 and ABA in vegetative tissue. Significant differences in histone
      modifications at the phas promoter were mediated by FUS3 and PvALF, suggesting
      that they function through different epigenetic mechanisms. The relationship
      between PvALF and ABI5, a bZIP transcription factor, in mediating phas expression
      was also evaluated. Interestingly, over-expression of ABI5 rendered phas
      expression ABA-independent in the presence of PvALF. Changes in phas activity in
      different regions within seed embryos were demonstrated using abi5 mutants. Our
      results show that (1) redundant factors, such as PvALF and FUS3, employ different
      mechanisms to regulate their common target gene (phas); (2) ABI5, and possibly
      other redundant bZIP factors, act downstream of ABA in modulating phas expression
      in the presence of PvALF.

PMID- 18038117
TI  - The scope of emergency paediatric surgery in Tanzania.
AB  - This article helps to outline the scope of emergency paediatric operations in
      Tanzania by quantifying the nature of cases seen over a 12 month period in a
      teaching hospital. Data collected at the Kilimanjaro Christian Medical Centre
      (KCMC) showed that operative paediatric surgical emergencies represented 4% of
      all paediatric admissions. Of emergency procedures, 47 (43%) were for congenital
      abnormalities, 32 (29%) for infections, 19 (17%) for trauma and 12 (11%) for
      other reasons. Emergency operative mortality was 34%. The challenges to meet
      patient needs in the African setting include: a scarcity of surgeons with
      training in paediatric surgery, the variety of conditions which all surgeons must
      manage, a lack of equipment (e.g., neonatal ventilators) and educational
      resources. Potential avenues for overcoming these challenges are discussed,
      including the promotion of paediatric surgery as a profession, by the expansion
      of existing facilities, promoting African associations of paediatric surgery and
      highlighting the need for resources and continued education and training. We
      argue that surgical training in developing countries should include the skills
      needed to treat those paediatric conditions most likely to require urgent
      surgical intervention.

PMID- 18038118
TI  - DNA (cytosine-5)-methyltransferase 1 as a mediator of mutant p53-determined
      p16(ink4A) down-regulation.
AB  - In cancer, gene silencing via hypermethylation is as common as genetic mutations
      in p53. Understanding the relationship between mutant p53 and hypermethylation of
      other tumor suppressor genes is essential when elucidate mechanisms of tumor
      development. In this study, two isogenic human B lymphoblast cell lines with
      different p53 status include TK6 containing wild-type p53 and WTK1 with mutant
      p53 were used and contrasted. Lower levels of p16(ink4A) protein were detected in
      WTK1 cells than in TK6 cells, which were accompanied by increased DNA (cytosine
      5)-methyltransferase 1 (DNMT1) gene expression as well as hypermethylation of the
      p16 ( ink4A ) promoter. siRNA experiments to transiently knock down wild-type p53
      in TK6 cells resulted in increase of DNMT1 expression as well as decrease of
      p16(ink4A) protein. Conversely, siRNA knockdown of mutant p53 in WTK1 cells did
      not alter either DNMT1 or p16(ink4A) protein levels. Furthermore, loss of
      suppression function of mutant p53 to DNMT1 in WTK1 was caused by the attenuation
      of its binding ability to the DNMT1 promoter. In summary, we provide evidences to
      elucidate the relationship between mutant p53 and DNMT1. Our results indicate
      that mutant p53 loses its ability to suppress DNMT1 expression, and thus enhances
      methylation levels of the p16 ( ink4A ) promoter and subsequently down-regulates
      p16(ink4A )protein.

PMID- 18038119
TI  - [Basal tako-tsubo cardiomyopathy. Induction of a pheochromocytoma after general
      anesthesia].
AB  - A 71-year-old female patient developed acute myocardial failure immediately after
      cataract surgery under general anesthesia. Subsequently performed
      laevocardiography demonstrated a basal ballooning of the left ventricle
      characteristic of basal tako-tsubo cardiomyopathy. The basal tako-tsubo
      cardiomyopathy was induced by a previously asymptomatic pheochromocytoma. The
      left ventricular function recovered completely within 4 days without specific
      treatment.

PMID- 18038120
TI  - [Not a fall--not abuse--not a rare finding?].
AB  - A baby was brought into the accident and emergency department with X-ray pictures
      and with a plaster cast in place because of a pain reaction in the right arm. The
      pictures showed destruction of the epiphyseal region and double periosteal
      contours. Alterations of the same kind were found in all long bones; they were
      recognized as compatible with florid congenital syphilis, which was confirmed by
      reference to the history and the laboratory findings and was successfully treated
      with penicillin G in the pediatric department. Both parents were also treated. No
      traumatological/orthopedic treatment was given, and the plaster cast was removed.
      Following recognition of the signs described a complete cure was possible.

PMID- 18038121
TI  - Ignoring the irrelevant: auditory tolerance of audible but innocuous sounds in
      the bat-detecting ears of moths.
AB  - Noctuid moths listen for the echolocation calls of hunting bats and respond to
      these predator cues with evasive flight. The African bollworm moth, Helicoverpa
      armigera, feeds at flowers near intensely singing cicadas, Platypleura capensis,
      yet does not avoid them. We determined that the moth can hear the cicada by
      observing that both of its auditory receptors (A1 and A2 cells) respond to the
      cicada's song. The firing response of the A1 cell rapidly adapts to the song and
      develops spike periods in less than a second that are in excess of those reported
      to elicit avoidance flight to bats in earlier studies. The possibility also
      exists that for at least part of the day, sensory input in the form of olfaction
      or vision overrides the moth's auditory responses. While auditory tolerance
      appears to allow H. armigera to exploit a food resource in close proximity to
      acoustic interference, it may render their hearing defence ineffective and make
      them vulnerable to predation by bats during the evening when cicadas continue to
      sing. Our study describes the first field observation of an eared insect ignoring
      audible but innocuous sounds.

PMID- 18038122
TI  - [Amyotrophic lateral sclerosis].
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, degenerative disease of the
      motor system characterized by signs and symptoms of upper and lower motor
      dysfunction. This results in the presence of focal amyotrophies and pareses
      affecting voluntary muscles. Patients die after a few years, in most cases by
      respiratory failure. ALS is the most frequent motor neuron disease; however, its
      etiology and pathogenesis are only known in fragments. Its genetic basis is only
      partially understood and major gaps remain in the understanding of its
      pathogenesis with the basic principle of selective vulnerability and potentially
      resulting therapeutic consequences.

PMID- 18038124
TI  - At the frontline of Alzheimer's disease treatment: gamma-secretase
      inhibitor/modulator mechanism.
AB  - Genetic and biological studies provide evidence that the production and
      deposition of amyloid-beta peptides (Abeta) contribute to the etiology of
      Alzheimer's disease. beta- and gamma-secretases, which are responsible for the
      generation of Abeta, are plausible molecular targets for Alzheimer's disease
      treatment. gamma-Secretase is an unusual aspartic protease that cleaves the
      scissile bond within the transmembrane domain. This unusual enzyme is composed of
      a high molecular weight membrane protein complex containing presenilin,
      nicastrin, Aph-1 and Pen-2. Drugs that regulate the production of Abeta by
      inhibiting or modulating gamma-secretase activity could provide a disease
      modifying effect on Alzheimer's disease, although recent studies suggest that
      gamma-secretase plays important roles in cellular signaling including Notch.
      Thus, understanding the molecular mechanism whereby gamma-secretase recognizes
      and cleaves its substrate is a critical issue for the development of compounds
      that specifically regulate Abeta-generating gamma-secretase activity. This review
      focuses on the structure and function relationship of gamma-secretase complex and
      the mode of action of the gamma-secretase inhibitors.

PMID- 18038127
TI  - Auditory-motor and cognitive aspects in area 8B of macaque monkey's frontal
      cortex: a premotor ear-eye field (PEEF).
AB  - In previous reports, we showed the involvement of area 8B neurons in both
      spontaneous ear and eye movement and in auditory information processing. Audition
      related cells responded to complex environmental stimuli, but not to pure tones,
      and their activity changed during visual fixation as a possible inhibitory
      expression of the engagement of attention. We observed auditory, auditory-motor
      and motor cells for both eye and ear movements. This finding suggests that area
      8B may be involved in the integration of auditory input with ear and eye motor
      output. In this paper, we extended these previous studies by examining area 8B
      activity in relation to auditive orienting behaviour, as well as the ocular
      orientation (i.e., visual fixation) studied previously. Visual fixation led to
      inhibition of activity in auditory and auditory-motor cells, which suggests that
      attention may be involved in both, maintaining the eye position and reducing the
      response of these cell types. Accordingly, during a given task or natural
      behaviour, spatial attention seems to affect more than one sensorimotor channel
      simultaneously. These data add to our understanding of how the neural network,
      through a two-channel attentive process, accomplishes to switch between two
      effectors, namely eyes and ears. Considering the functional, anatomical and
      cytoarchitectonic differences among the frontal eye field (FEF), the
      supplementary eye field (SEF) and area 8B, we propose to consider area 8B as a
      separate premotor ear-eye field (PEEF).

PMID- 18038126
TI  - Noradrenergic-glucocorticoid mechanisms in emotion-induced amnesia: from
      adaptation to disease.
AB  - DISCUSSIONS: The interaction of emotion and episodic encoding has costs and
      benefits. These costs and benefits have been characterized in oddball
      experiments, where a violation of prevailing neutral context through aversive
      oddballs is associated with subsequent hypermnesia for the aversive oddball and
      peri-emotional amnesia for the neutral context. Both hypermnesia and peri
      emotional amnesia are amygdala-dependent and vary as a function of noradrenergic
      glucocorticoid input to the amygdala during emotional episodic encoding.
      Pharmacological enhancement of this input allows to model the maladaptive effects
      of emotion on episodic encoding. Extrapolation of these findings to conditions of
      emotional trauma suggests that disinhibited noradrenergic-glucocorticoid
      signaling could serve as a crucial etiological contributor to the pathogenesis of
      peri-traumatic amnesia (PTA) and post-traumatic stress disorder (PTSD).
      CONCLUSIONS: Immediate pharmacological blockade of noradrenergic-glucocorticoid
      signaling might prove effective in the secondary prevention of PTA and PTSD.

PMID- 18038128
TI  - Dissociation of early evoked cortical activity in perceptual grouping.
AB  - Perceptual grouping is a multi-stage process, irreducible to a single mechanism
      localized anatomically or chronometrically. To understand how various grouping
      mechanisms interact, we combined a phenomenological report paradigm with high
      density event-related potential (ERP) measurements, using a 256-channel electrode
      array. We varied the relative salience of competing perceptual organizations in
      multi-stable dot lattices and asked observers to report perceived groupings. The
      ability to discriminate groupings (the grouping sensitivity) was positively
      correlated with the amplitude of the earliest ERP peak C1 (about 60 ms after
      stimulus onset) over the middle occipital area. This early activity is believed
      to reflect spontaneous feed-forward processes preceding perceptual awareness.
      Grouping sensitivity was negatively correlated with the amplitude of the next
      peak P1 (about 110 ms), which is believed to reflect lateral and feedback
      interactions associated with perceptual awareness and attention. This
      dissociation between C1 and P1 activity implies that the recruitment of fast,
      spontaneous mechanisms for grouping leads to high grouping sensitivity. Observers
      who fail to recruit these mechanisms are trying to compensate by using later
      mechanisms, which depend less on stimulus properties such as proximity.

PMID- 18038129
TI  - A domain peptide of the cardiac ryanodine receptor regulates channel sensitivity
      to luminal Ca2+ via cytoplasmic Ca2+ sites.
AB  - The clustering of cardiac RyR mutations, linked to sudden cardiac death (SCD),
      into several regions in the amino acid sequence underlies the hypothesis that
      these mutations interfere with stabilising interactions between different domains
      of the RyR2. SCD mutations cause increased channel sensitivity to cytoplasmic and
      luminal Ca(2+). A synthetic peptide corresponding to part of the central domain
      (DPc10:(2460)G-P(2495)) was designed to destabilise the interaction of the N
      terminal and central domains of wild-type RyR2 and mimic the effects of SCD
      mutations. With Ca(2+) as the sole regulating ion, DPc10 caused increased channel
      activity which could be reversed by removal of the peptide whereas in the
      presence of ATP DPc10 caused no activation. In support of the domain destablising
      hypothesis, the corresponding peptide (DPc10-mut) containing the CPVT mutation
      R2474S did not affect channel activity under any circumstances. DPc10-induced
      activation was due to a small increase in RyR2 sensitivity to cytoplasmic Ca(2+)
      and a large increase in the magnitude of luminal Ca(2+) activation. The increase
      in the luminal Ca(2+) response appeared reliant on the luminal-to-cytoplasmic
      Ca(2+) flux in the channel, indicating that luminal Ca(2+) was activating the
      RyR2 via its cytoplasmic Ca(2+) sites. DPc10 had no significant effect on the
      RyR2 gating associated with luminal Ca(2+) sensing sites. The results were fitted
      by the luminal-triggered Ca(2+) feed-through model and the effects of DPc10 were
      explained entirely by perturbations in cytoplasmic Ca(2+)-activation mechanism.

PMID- 18038130
TI  - Novel peroxidases of Marasmius scorodonius degrade beta-carotene.
AB  - Two extracellular enzymes (MsP1 and MsP2) capable of efficient beta-carotene
      degradation were purified from culture supernatants of the basidiomycete
      Marasmius scorodonius (garlic mushroom). Under native conditions, the enzymes
      exhibited molecular masses of approximately 150 and approximately 120 kDa,
      respectively. SDS-PAGE and mass spectrometric data suggested a composition of two
      identical subunits for both enzymes. Biochemical characterisation of the purified
      proteins showed isoelectric points of 3.7 and 3.5, and the presence of heme
      groups in the active enzymes. Partial amino acid sequences were derived from N
      terminal Edman degradation and from mass spectrometric ab initio sequencing of
      internal peptides. cDNAs of 1,604 to 1,923 bp, containing open reading frames
      (ORF) of 508 to 513 amino acids, respectively, were cloned from a cDNA library of
      M. scorodonius. These data suggest glycosylation degrees of approximately 23% for
      MsP1 and 8% for MsP2. Databank homology searches revealed sequence homologies of
      MsP1 and MsP2 to unusual peroxidases of the fungi Thanatephorus cucumeris (DyP)
      and Termitomyces albuminosus (TAP).

PMID- 18038131
TI  - Biologically active components and nutraceuticals in the Monascus-fermented rice:
      a review.
AB  - Monascus-fermented rice has traditionally been used as a natural food colorant
      and food preservative of meat and fish for centuries. It has recently become a
      popular dietary supplement because of many of its bioactive constituents being
      discovered, including a series of active drug compounds, monacolins, indicated as
      the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors for reducing serum
      cholesterol level. The controversy of its safety has been provoked because a
      mycotoxin, citrinin, is also produced along with the Monascus secondary
      metabolites by certain strains or under certain cultivation conditions. This
      review introduces the basic production process and addresses on the compounds
      with bioactive functions. Current advances in avoiding the harmful ingredient
      citrinin are also discussed.

PMID- 18038132
TI  - Labeling peptides with PET radiometals: Vulcan's forge.

PMID- 18038133
TI  - (68)Ga-DOTAVAP-P1 PET imaging capable of demonstrating the phase of inflammation
      in healing bones and the progress of infection in osteomyelitic bones.
AB  - PURPOSE: Differentiation between bacterial infection and nonbacterial
      inflammation remains a diagnostic challenge. Vascular adhesion protein 1 (VAP-1)
      is a human endothelial protein whose cell surface expression is induced under
      inflammatory conditions, thus making it a highly promising target molecule for
      studying inflammatory processes in vivo. We hypothesized that positron emission
      tomography (PET) with gallium-68-labeled 1,4,7,10-tetraazacyclododecane
      N',N'',N''',N''''-tetraacetic acid-peptide targeted to VAP-1 ((68)Ga-DOTAVAP-P1)
      could be feasible for imaging the early inflammatory and infectious processes in
      healing bones. MATERIALS AND METHODS: Thirty-four Sprague-Dawley rats with
      diffuse Staphylococcus aureus tibial osteomyelitis and 34 rats with healing
      cortical bone defects (representing the inflammation stage of healing) were PET
      imaged using (68)Ga-DOTAVAP-P1 as a tracer. In addition, peripheral quantitative
      computed tomography and conventional radiography were performed. Bone samples for
      quantitative bacteriology and specimens were also processed for histomorphometry
      of inflammatory and infectious reactions. RESULTS: PET imaging showed an uptake
      of (68)Ga-DOTAVAP-P1 in both the osteomyelitic bones and the healing cortical
      bone defects during the first 36 h after surgery. Thereafter, only the
      osteomyelitic tibias were delineated by PET. The osteomyelitic and control
      animals showed a similar uptake of the (68)Ga-DOTAVAP-P1 at 24 h, whereas a
      significant difference was observed at 7 days (p < 0.0001). CONCLUSIONS: The
      current study showed that PET imaging with the new (68)Ga-DOTAVAP-P1 is capable
      of accurately demonstrating the phase of inflammation in healing bones and the
      progress of bacterial infection in osteomyelitic bones. Consequently, this novel
      imaging agent allowed for the differentiation of bone infection due to S. aureus
      and normal bone healing as soon as 7 days after onset.

PMID- 18038134
TI  - The role of polymerase chain reaction in the management of osteoarticular
      tuberculosis.
AB  - A dependable method for the rapid diagnosis of osteoarticular tuberculosis has
      become increasingly important, as routine methods are neither very sensitive nor
      very specific. The objective of this study is to verify the reliability of
      polymerase chain reaction (PCR) in the diagnosis and management of osteoarticular
      tuberculosis. This investigation was a prospective study conducted at the
      Kasturba Medical College, Manipal, India. Tissue samples of 74 patients suspected
      of osteoarticular tuberculosis were sent for PCR and histopathologic examination.
      Taking histopathology as the gold standard, PCR has a sensitivity of 73.07% and a
      specificity of 93.75% (with 95% confidence interval [CI] 62.97; 83.17).The
      positive agreement between histology and PCR was 0.693, indicating good
      agreement. PCR showed a sensitivity of 90% with spinal samples. It has a low
      false positivity of 13.63%. We conclude that conventional methods are neither
      sensitive nor specific enough and are also time consuming. PCR is an effective
      method for diagnosing tuberculosis and antitubercular treatment can be started if
      PCR is positive, since false-positive rates are very low.

PMID- 18038135
TI  - Biological approach to treatment of intra-articular proximal tibial fractures
      with double osteosynthesis.
AB  - The treatment of intra-articular proximal tibial fractures is associated with
      complications, and much conflicting literature exists concerning the treatment of
      choice. In our study, an attempt has been made to develop an ideal and adequate
      treatment protocol for these intra-articular fractures. The principle of double
      osteosynthesis, i.e., lateral minimally invasive plate osteosynthesis (MIPO), was
      combined with a medial external fixator to treat 22 intra-articular proximal
      tibial fractures with soft tissue injury with a mean follow-up of 25 months.
      Superficial pin track infection was observed in one case, and no soft tissue
      breakdown was noted. Loss of articular reconstruction was reported in one case.
      Bridging callus was seen at 12 weeks (8 weeks-7 months). The principle of
      substitution or double osteosynthesis, i.e., lateral MIPO, was combined with a
      medial external fixator and proved to be a fairly good method of fixation in
      terms of results and complications.

PMID- 18038136
TI  - Henoch-Schonlein purpura in a patient with human immunodeficiency virus
      infection.
AB  - We encountered an adult patient with Henoch-Schonlein purpura. He had been
      infected with human immunodeficiency virus (HIV) and antiretroviral therapy
      improved his nephritis, indicating that HIV infection might have contributed to
      the development of Henoch-Schonlein purpura in our case.

PMID- 18038125
TI  - Novel pharmacological approaches to the treatment of renal ischemia-reperfusion
      injury: a comprehensive review.
AB  - Renal ischemia-reperfusion (I-R) contributes to the development of ischemic acute
      renal failure (ARF). Multi-factorial processes are involved in the development
      and progression of renal I-R injury with the generation of reactive oxygen
      species, nitric oxide and peroxynitrite, and the decline of antioxidant
      protection playing major roles, leading to dysfunction, injury, and death of the
      cells of the kidney. Renal inflammation, involving cytokine/adhesion molecule
      cascades with recruitment, activation, and diapedesis of circulating leukocytes
      is also implicated. Clinically, renal I-R occurs in a variety of medical and
      surgical settings and is responsible for the development of acute tubular
      necrosis (a characteristic feature of ischemic ARF), e.g., in renal
      transplantation where I-R of the kidney directly influences graft and patient
      survival. The cellular mechanisms involved in the development of renal I-R injury
      have been targeted by several pharmacological interventions. However, although
      showing promise in experimental models of renal I-R injury and ischemic ARF, they
      have not proved successful in the clinical setting (e.g., atrial natriuretic
      peptide, low-dose dopamine). This review highlights recent pharmacological
      developments, which have shown particular promise against experimental renal I-R
      injury and ischemic ARF, including novel antioxidants and antioxidant enzyme
      mimetics, nitric oxide and nitric oxide synthase inhibitors, erythropoietin,
      peroxisome-proliferator-activated receptor agonists, inhibitors of poly(ADP
      ribose) polymerase, carbon monoxide-releasing molecules, statins, and adenosine.
      Novel approaches such as recent research involving combination therapies and the
      potential of non-pharmacological strategies are also considered.

PMID- 18038137
TI  - Celiac disease in a rheumatology unit: a case study.
AB  - The objective of the study is to present a series of 20 patients who have been
      attending a rheumatology unit and were diagnosed with celiac disease in adult
      life. The record-charts of 20 Italian not consanguineous patients affected by
      celiac disease (1 man and 19 women, mean age of 46.7), diagnosed at >16 years of
      age, followed by a rheumatology unit were reviewed (group 1). Any other
      autoimmune disease diagnosed in the patients were given was recorded; moreover,
      the reason for rheumatologist evaluation was registered as well as the presence
      of symptoms suggestive of celiac disease and the obstetric history. The clinical
      features were compared with those of a group of 40 celiac patients (8 men and 32
      women, mean age of 43.1) followed by a medicine department (group 2); even in
      these cases the diagnosis of celiac disease was performed in adult life. Sixteen
      out of 20 patients in Group 1 were diagnosed as suffering from celiac disease by
      the rheumatologist. Seventeen concomitant autoimmune disorders among which nine
      were connective tissue diseases were found in 15 patients. The main reason for
      rheumatologist evaluation was arthromyalgias. Ten patients showed one or more
      clinical features suggestive of celiac disease; moreover, eight patients had a
      history of sideropenic anemia. After the adoption of a gluten-free diet there
      were three pregnancies that all ended with alive newborns, differently from the
      obstetric history before celiac disease diagnosis, characterized by a relevant
      number of miscarriages and foetus deaths. In Group 2, a total of ten autoimmune
      diseases concomitant with celiac disease were found in eight patients; autoimmune
      thyroid disorders represented the most frequent cases. No connective tissue
      diseases were recognized. Celiac disease may coexist with connective tissue
      diseases; the recognition of this association is difficult because celiac disease
      may present with atypical or even symptomless forms or in some cases may resemble
      a multisystem disorder or may mimic a rheumatologic condition; on the other hand,
      the variety of symptoms of rheumatic disorders may make difficult the diagnosis
      of celiac disease in association with a systemic autoimmune disease. These
      confounding factors often lead to a delay in performing the right diagnostic
      formulation.

PMID- 18038138
TI  - Primary hypertrophic osteoarthropathy with myelofibrosis.
AB  - Primary hypertrophic osteoarthropathy or pachydermoperiostosis is a rare
      congenital disease characterized by clubbing of the fingers, periostitis of the
      distal long bones, and hypertrophic skin changes (pachydermia) including thick
      folds in the skin of the face, forehead, scalp and extremities, and also joint
      pain. Clinical manifestations of this disease generally appear among the young
      and middle-aged. In this article we report a case of a 43-year-old man with
      pachydermoperiostosis. His skin and joint manifestations were prominent. He had
      also anemia, and bone marrow biopsy showed myelofibrosis.

PMID- 18038139
TI  - [Measurement of the central corneal power after myopic LASIK].
AB  - PURPOSE: Comparison of the central corneal refractive power before and after
      myopic LASIK using the Keratograph and the Pentacam. The Scheimpflug technique
      (Pentacam) enables the measurement of the corneal refractive power by examining
      the anterior and posterior corneal curvature. METHOD: The corneal refractive
      power of 59 eyes was examined before, 3 months and 6 months after myopic LASIK.
      The refractive power was measured at the corneal apex and at a distance of 2 and
      4 mm. Statistical analysis was performed using the Wilcoxon signed rank test; a p
      value of 0.05 or less was considered statistically significant. RESULTS: At the
      corneal apex and at a distance of 2 mm the findings with the Keratograph showed a
      higher refractive power of up to 1.05 D. The differences were statistically
      significant at all times. At a distance of 4 mm from the corneal apex
      postoperatively there was no statistically significant difference. CONCLUSION:
      The results using the Pentacam system showed a lower corneal refractive power
      following myopic LASIK at all times. Its measuring principle compared to that of
      the Keratograph should be preferred when detecting changes of the refractive
      power of the central cornea after corneal refractive procedures.

PMID- 18038140
TI  - Role of arylalkylamine N-acetyltransferase in regulation of biogenic amines
      levels by gonadotropins in Drosophila.
AB  - The effect of 20-hydroxyecdysone (20E) and the juvenile hormone (JH) on the
      activity of the arylalkylamine N-acetyltransferase (AANAT) was studied in young
      females of wild-type D. virilis and D. melanogaster. 20E feeding of the flies led
      to a decrease in AANAT activity in both species when dopamine (DA) was used as
      substrate, but did not affect the enzyme activity when octopamine (OA) was used
      as substrate. JH application increased AANAT activity with DA as substrate in
      both species, but did not change it with OA as substrate. AANAT activity was also
      measured in young females of a JH-deficient strain of D. melanogaster, apterous (
      56f ). A decrease in the enzyme activity was observed in the mutant females as
      compared to wild-type. Mechanisms of regulation of DA level by gonadotropins in
      Drosophila are discussed.

PMID- 18038141
TI  - Acromioclavicular dislocation Rockwood III-V: results of early versus delayed
      surgical treatment.
AB  - INTRODUCTION: The management of acute acromioclavicular joint (ACJ-) injuries
      especially of type III is still controversial. METHODS: In this retrospective
      study the results of early ACJ reconstructions immediately after trauma (group
      early repair, ER) were compared with the results of delayed reconstructions in
      patients who first got conservative treatment and failed after some time (group
      delayed repair, DR). Overall, 49 patients were analysed clinically and
      radiographically with a mean follow-up of 53 months (range 20-92). In group ER
      twenty-nine patients were treated with a modified Phemister technique according
      to Mayr including a PDS coracoclavicular sling and temporary K- wire fixation. In
      group DR twenty patients were treated with a modified Weaver-Dunn-procedure with
      additionally transposition of the coracoacromial ligament and AC-joint resection.
      RESULTS: A comparison of the overall results revealed a statistically significant
      better outcome in the early repair group, regarding the Constant Score, the
      degree of acromioclavicularjoint-reduction, numbers of complications and
      patient;s satisfaction. CONCLUSION: Our results point out that early
      reconstruction of ACJ-injuries in type III-V avoids the inferior clinical results
      of delayed reconstructions using a modified Weaver-Dunn-procedure.

PMID- 18038142
TI  - Comparison of periprosthetic bone remodelling after implantation of anatomic and
      straight stem prostheses in total hip arthroplasty.
AB  - INTRODUCTION: Total hip arthroplasty changes bone loading conditions in the
      proximal femur and induces adaptive remodelling of the periprosthetic bone. These
      remodelling processes depend on many implant-specific qualities, e.g. material
      and elasticity of the stem. The objective of this study was to investigate the
      effect of the stem design on periprosthetic bone remodelling after insertion of
      an anatomic stem with proximal fixation and the direct comparison to a straight
      stem prosthesis. MATERIALS AND METHODS: In a prospective study, the changes in
      periprosthetic bone mineral density (BMD) after implantation of 68 CTX-S anatomic
      and 22 PPF straight stem prostheses were assessed in the first post-operative
      year by means of DEXA and zone analysis by Gruen (Clin Orthop 141:17-27, 1979)
      "Modes of failure" of cemented stem-type femoral components: a radiographic
      analysis of loosening. Furthermore all patients with CTX-S prostheses were
      monitored in the second post-operative year. The correlation of adaptive bone
      remodelling and the systemic bone density was also investigated. RESULTS: In the
      distal one-third of the straight stem prosthesis, a clearly greater, although not
      significant, hypertrophy of the periprosthetic bone was observed. No differences
      in the extent of bone loss between the two prostheses in the regions of interest
      (ROI) of the proximal bone were observed. The greatest decrease in BMD was
      registered in the medial femoral neck in both groups. Bone atrophy decreased
      progressively as the ROI moved distally, ending in a slight increase in BMD in
      the distal ROI. No significant changes in periprosthetic BMD occurred in the
      second post-operative year. A strong positive correlation in the regions with the
      greatest BMD decrease with the systemic BMD was ascertained. CONCLUSION: After
      implanting a CTX-S prosthesis, as opposed to PPF prostheses, a different pattern
      of periprosthetic bone remodelling with a slighter hypertrophy of the distal
      periprosthetic parts was observed. This implies that the extensive proximal, more
      physiological bone loading of the anatomic stem as well as the removal of less
      bone while implanting the stem reduces the negative effects of unphysiological
      strain distribution and stress shielding. The BMD loss in the medial proximal
      neck cannot be avoided with this stem design either. The lack of significant BMD
      changes in the second post-operative year suggests that a stabilisation of bone
      remodelling processes occurs.

PMID- 18038143
TI  - Improved tolerability of open carpal tunnel release under local anaesthetic: a
      patient satisfaction survey.
AB  - Carpal tunnel decompression is the most commonly performed procedure in hand
      surgery. This study was done to assess the effectiveness and acceptability by
      patients of open carpal tunnel release under local anaesthetic. We compare our
      results with both the literature and those of our previous study, after which
      were made alterations to improve the surgical and anaesthetic technique. These
      alterations included (a) injecting local anaesthetic with a dental syringe and a
      27G needle in two stages along the proposed line of the incision and (b) omitting
      the use of a tourniquet, relying on the local anaesthetic with adrenaline to
      maintain a bloodless field during the procedure.

PMID- 18038144
TI  - A schwannoma in the nasal septum.
AB  - Schwannomas of the sinonasal tract are very rare neoplasms. We present the case
      of a schwannoma developing in the nasal septum. The patient was a 51-year-old
      woman with the complaint of unilateral nasal obstruction. We completely removed
      this tumor by an endoscopic approach. We discuss the clinical presentation,
      differential diagnosis, and treatment of this rarely encountered neoplasm.

PMID- 18038145
TI  - Neural model of disinhibitory interactions in the modified Poggendorff illusion.
AB  - Visual illusions can be strengthened or weakened with the addition of extra
      visual elements. For example, in the Poggendorff illusion, with an additional bar
      added, the illusory skew in the perceived angle can be enlarged or reduced. In
      this paper, we show that a nontrivial interaction between lateral inhibitory
      processes in the early visual system (i.e., disinhibition) can explain such an
      enhancement or degradation of the illusory effect. The computational model we
      derived successfully predicted the perceived angle in the Poggendorff illusion
      task that was modified to include an extra thick bar. The concept of
      disinhibition employed in the model is general enough that we expect it can be
      further extended to account for other classes of geometric illusions.

PMID- 18038147
TI  - Anomalous left coronary artery from pulmonary artery (ALCAPA) in infants: a 5
      year review in a defined birth cohort.
AB  - Anomalous left coronary artery from pulmonary artery (ALCAPA) is a rare
      congenital cardiac malformation. It presents predominantly in infancy with
      features of myocardial ischaemia or cardiac failure and may be mistaken for
      common paediatric conditions such as colic, reflux or bronchiolitis. With early
      surgical correction the prognosis is good, but awareness of this condition is
      essential for prompt diagnosis and referral to a tertiary cardiac centre. In this
      report we review the five cases that presented during our 5-year study period and
      discuss the incidence and clinical presentation of ALCAPA among infants. Our
      observed incidence of 1 in 4243 live births--0.023%--is higher than previously
      reported. ALCAPA may be more common than previously recognised, and there should
      be a high index of awareness among paediatricians, paediatric trainees and
      general practitioners to enable early surgical intervention and improved
      prognosis for these children.

PMID- 18038146
TI  - Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and
      recommendations for treatment in the era of enzyme replacement therapy.
AB  - Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked
      recessive disease caused by deficiency of the lysosomal enzyme iduronate-2
      sulphatase, leading to progressive accumulation of glycosaminoglycans in nearly
      all cell types, tissues and organs. Clinical manifestations include severe airway
      obstruction, skeletal deformities, cardiomyopathy and, in most patients,
      neurological decline. Death usually occurs in the second decade of life, although
      some patients with less severe disease have survived into their fifth or sixth
      decade. Until recently, there has been no effective therapy for MPS II, and care
      has been palliative. Enzyme replacement therapy (ERT) with recombinant human
      iduronate-2-sulphatase (idursulfase), however, has now been introduced. Weekly
      intravenous infusions of idursulfase have been shown to improve many of the signs
      and symptoms and overall wellbeing in patients with MPS II. This paper provides
      an overview of the clinical manifestations, diagnosis and symptomatic management
      of patients with MPS II and provides recommendations for the use of ERT. The
      issue of treating very young patients and those with CNS involvement is also
      discussed. ERT with idursulfase has the potential to benefit many patients with
      MPS II, especially if started early in the course of the disease.

PMID- 18038148
TI  - Bartter syndrome and cholelithiasis in an infant: is this a mere coincidence?

PMID- 18038149
TI  - Molecular and cytogenetic evidence of three sibling species of the Anopheles
      barbirostris Form A (Diptera:Culicidae) in Thailand.
AB  - Nine isoline colonies of Anopheles barbirostris Form A, derived from individual
      isofemale lines from Chiang Mai, Phetchaburi, and Kanchanaburi, were established
      in our insectary at Chiang Mai University. All isolines shared the same mitotic
      karyotype (X(1), X(2), Y(1)). Molecular analysis of deoxyribonucleic acid (DNA)
      sequences and polymerase chain reaction (PCR) products of ITS2, COI, and COII
      regions revealed three distinct groups: A1 (Chiang Mai), A2 (Phetchaburi), and A3
      (Kanchanaburi). Crossing experiments among the three groups exhibited strong
      reproductive isolation, producing low and/or non-hatched eggs, and inviable
      and/or abnormal development of the reproductive system of F(1)-progenies.
      Asynaptic regions along the five polytene chromosome arms of F(1)-hybrid larvae
      clearly supported the existence of three sibling species within A. barbirostris
      Form A, provisionally named species A1, A2, and A3.

PMID- 18038151
TI  - The profile of IgG-antibody response against merozoite surface proteins 1 and 2
      in severe Plasmodium falciparum malaria in Eastern Sudan.
AB  - In this study, antibodies (Ab) directed against three MSP antigens; MSP1(19),
      MSP2(A), and MSP2(B) were analyzed in blood samples obtained from 223 Sudanese
      patients who presented with either severe malaria (SM) or uncomplicated malaria
      (UM) and from 117 malaria-free donors (MF). The results showed that the
      prevalence of MSP Abs was associated with the clinical outcome of malaria
      infection, and the Ab prevalence was age-dependent (P<0.0005). More importantly,
      the prevalence of MSP Abs against the test antigens was lower in SM compared to
      UM (P=0.001 to 0.020), suggesting a protective role for these Abs against SM.
      Furthermore, the Ab responses between individual complications of SM were
      significantly different.

PMID- 18038150
TI  - Diagnosis of Plasmodium falciparum malaria in pregnancy in sub-Saharan Africa:
      the challenges and public health implications.
AB  - Plasmodium falciparum malaria in pregnancy is a major public health problem in
      sub-Saharan Africa and represents enormous diagnostic challenge. The objective of
      this report was to review scientific data from studies conducted in sub-Saharan
      Africa on the diagnosis of malaria in pregnancy within the last two decades (1987
      to 2007), to highlight the challenges and the public health implications. Using
      the Medline Entrez-Pubmed search, relevant publications were identified for the
      review via combinations of key words such as Malaria, Pregnancy, and Sub-Saharan
      Africa, which yielded 777 entries as of September 2007. The results from the
      various studies were discordant, due to differences in the techniques of sample
      collection and analysis, based on the differences in the definition of clinical,
      peripheral, and placental malaria. Definitions were based on the presence of
      malaria parasite and/or pigments in blood smear from peripheral/placental blood,
      on histological placental findings, on the use of rapid diagnostic tests (RDTs)
      and polymerase chain reaction (PCR). Nonspecific clinical presentation of
      malaria, lack of efficient diagnostic facilities and trained personnel, and
      absence of regulatory standards for diagnostic tests, are some of the major
      diagnostic challenges. Increased allocation of resources to development and
      application of accurate diagnostics will improve malaria diagnosis in pregnancy.

PMID- 18038152
TI  - Promoter methylation study of the H37/RBM5 tumor suppressor gene from the 3p21.3
      human lung cancer tumor suppressor locus.
AB  - Loss of heterozygosity (LOH) at chromosome 3p21.3 is one of the most prevalent
      genetic disturbances occurring at the earliest stage of tumor development for a
      wide variety of human cancers, culminated in lung cancer. The 19 genes residing
      at 3p21.3 have been vigorously characterized for tumor suppressor activity and
      gene inactivation mechanism because of their potentially significant merits of
      clinical applications. Many of these 19 genes have been shown to manifest various
      growth inhibitory properties, however none of them are inactivated by coding
      mutations in their remaining allele as in the Knudson's two- hits hypothesis.
      Thus far the most prevailing, alternative gene inactivation mechanism known for
      the 3p21.3 TSGs is epigenetic silencing by promoter hypermethylation. Previously,
      we have focused our investigation on one of the 19 genes at 3p21.3, H37/RBM5, and
      demonstrated its tumor suppressor activity both in vitro and in vivo as well as
      its mRNA/protein expression loss from the remaining allele in a majority of the
      primary lung tumors examined. The current study tested our hypothesis that the
      H37 inactivation in primary lung tumors may, as seen in most of the other 3p21.3
      TSGs, be due to hypermethylation in its promoter CpG islands. Contrary to this
      most plausible postulation, however, we found no evidence of epigenetic gene
      silencing for the H37 TSG. Here we suggest some of the possible, further-
      alternative means of the H37 gene expression loss in tumor, including defects in
      transcription and post-transcriptional/translational modifications as well as
      mechanisms related to haploinsufficiency.

PMID- 18038154
TI  - Density-related variation in vertical transmission of a virus in the African
      armyworm.
AB  - Larvae of the African armyworm, Spodoptera exempta, are darker and more resistant
      to baculovirus infection when reared in groups (gregarious form) compared to
      being reared singly (solitary form). Lepidoptera that survive virus challenge as
      larvae could potentially retain a sublethal virus infection which is then
      transmitted vertically to the next generation. Here we examine whether gregarious
      and solitary forms of the armyworm differ in the costs of surviving virus
      infection and in their capacity to transmit an active baculovirus infection to
      their offspring. Pupae of larvae reared gregariously that survived virus
      challenge weighed significantly less than uninfected individuals, but this was
      not so for those reared solitarily. This did not, however, translate into
      differences in fecundity, at least under laboratory conditions. As found in
      previous studies, pre-oviposition period was shorter for solitary than gregarious
      insects, and it was also shorter for females that had been challenged with virus
      as larvae. Both the prevalence of egg batches containing larvae that died from
      nucleopolyhedrovirus (NPV) infection and the proportion of infected larvae within
      each egg batch were significantly increased (approximately doubled) when parental
      moths were previously challenged with the virus during their larval state. This
      demonstrates that horizontal transmission in one generation can elevate vertical
      transmission to the next generation. Moreover, prevalence of overt infection in
      the offspring generation was two to three times greater when parental moths were
      reared solitarily as larvae than when reared gregariously. Disease prevalence and
      proportional infection were both independent of the sex of the infected parent
      and whether or not the egg batch was surface-sterilized to remove potential
      contaminants. This suggests that the eggs are infected internally (transovarial)
      rather than externally (transovum). These results help to shed light on the
      observed temporal pattern of virus epizootics in eastern Africa.

PMID- 18038153
TI  - Mendelian randomization: can genetic epidemiology help redress the failures of
      observational epidemiology?
AB  - Establishing causal relationships between environmental exposures and common
      diseases is beset with problems of unresolved confounding, reverse causation and
      selection bias that may result in spurious inferences. Mendelian randomization,
      in which a functional genetic variant acts as a proxy for an environmental
      exposure, provides a means of overcoming these problems as the inheritance of
      genetic variants is independent of-that is randomized with respect to-the
      inheritance of other traits, according to Mendel's law of independent assortment.
      Examples drawn from exposures and outcomes as diverse as milk and osteoporosis,
      alcohol and coronary heart disease, sheep dip and farm workers' compensation
      neurosis, folate and neural tube defects are used to illustrate the applications
      of Mendelian randomization approaches in assessing potential environmental causes
      of disease. As with all genetic epidemiology studies there are problems
      associated with the need for large sample sizes, the non-replication of findings,
      and the lack of relevant functional genetic variants. In addition to these
      problems, Mendelian randomization findings may be confounded by other genetic
      variants in linkage disequilibrium with the variant under study, or by population
      stratification. Furthermore, pleiotropy of effect of a genetic variant may result
      in null associations, as may canalisation of genetic effects. If correctly
      conducted and carefully interpreted, Mendelian randomization studies can provide
      useful evidence to support or reject causal hypotheses linking environmental
      exposures to common diseases.

PMID- 18038155
TI  - Soil nutrients affect spatial patterns of aboveground biomass and emergent tree
      density in southwestern Borneo.
AB  - Studies on the relationship between soil fertility and aboveground biomass in
      lowland tropical forests have yielded conflicting results, reporting positive,
      negative and no effect of soil nutrients on aboveground biomass. Here, we
      quantify the impact of soil variation on the stand structure of mature Bornean
      forest throughout a lowland watershed (8-196 m a.s.l.) with uniform climate and
      heterogeneous soils. Categorical and bivariate methods were used to quantify the
      effects of (1) parent material differing in nutrient content (alluvium >
      sedimentary > granite) and (2) 27 soil parameters on tree density, size
      distribution, basal area and aboveground biomass. Trees > or =10 cm (diameter at
      breast height, dbh) were enumerated in 30 (0.16 ha) plots (sample area = 4.8 ha).
      Six soil samples (0-20 cm) per plot were analyzed for physiochemical properties.
      Aboveground biomass was estimated using allometric equations. Across all plots,
      stem density averaged 521 +/- 13 stems ha(-1), basal area 39.6 +/- 1.4 m(2) ha(
      1) and aboveground biomass 518 +/- 28 Mg ha(-1) (mean +/- SE). Adjusted forest
      wide aboveground biomass to account for apparent overestimation of large tree
      density (based on 69 0.3-ha transects; sample area = 20.7 ha) was 430 +/- 25 Mg
      ha(-1). Stand structure did not vary significantly among substrates, but it did
      show a clear trend toward larger stature on nutrient-rich alluvium, with a higher
      density and larger maximum size of emergent trees. Across all plots, surface soil
      phosphorus (P), potassium, magnesium and percentage sand content were
      significantly related to stem density and/or aboveground biomass (R (Pearson) =
      0.368-0.416). In multiple linear regression, extractable P and percentage sand
      combined explained 31% of the aboveground biomass variance. Regression analyses
      on size classes showed that the abundance of emergent trees >120 cm dbh was
      positively related to soil P and exchangeable bases, whereas trees 60-90 cm dbh
      were negatively related to these factors. Soil fertility thus had a significant
      effect on both total aboveground biomass and its distribution among size classes.

PMID- 18038156
TI  - Steroid-responsive nephrotic syndrome in a child with juvenile idiopathic
      arthritis.
AB  - Renal disease is rare in children with juvenile idiopathic arthritis, although a
      number of associated nephropathies have been described, including mesangial
      glomerulonephritis. We report the presence of mesangial glomerulonephritis,
      revealed by a nephrotic syndrome, in a paediatric patient with juvenile
      idiopathic arthritis. Short-term steroid treatment induced a rapid remission of
      the nephrotic syndrome, but the presence of anti-nuclear antibodies, 1:320 in a
      homogeneous pattern, irregular deposits of C1q in a renal biopsy, and a mother
      with episodes of cutaneous lupus suggested an uncertain renal evolution for this
      infant.

PMID- 18038157
TI  - Ischemic colitis as a complication in a patient with steroid-dependent nephrotic
      syndrome.
AB  - We report the case of a 16-year-old male patient with steroid-dependent nephrotic
      syndrome who developed ischemic colitis. He was diagnosed as having nephrotic
      syndrome at 10 years of age and had been administered steroid, cyclosporine A,
      and mizoribine for 7 years. He presented with severe abdominal pain 5 days after
      intravenous methylprednisolone pulse therapy; thereafter, massive bloody diarrhea
      developed. Abdominal ultrasonography and computed tomography revealed a marked
      thickening of the wall of the transverse colon. Colonoscopy confirmed the
      diagnosis of ischemic colitis. This is the first report of the development of
      ischemic colitis in a pediatric patient with nephrotic syndrome.

PMID- 18038158
TI  - Use of mizoribine as a rescue drug for steroid-resistant pediatric IgA
      nephropathy.
AB  - Recent clinical trials have shown a beneficial effect of mizoribine (Miz), an
      immunosuppressive drug, in the treatment of new-onset pediatric IgA nephropathy
      (IgAN). In this study, we evaluated the efficacy of Miz treatment in three
      children with established steroid-resistant IgAN. The patients had IgAN featuring
      persistent proteinuria and diffuse mesangial proliferation and had failed to
      respond to 2 years of treatment with prednisolone. Based upon the second biopsy
      results, patients were given methylprednisolone (mPSL) pulse therapy that induced
      a transient reduction in proteinuria, which was reversed when the mPSL dose was
      tapered. Miz therapy was then instigated in place of pulse mPSL. All three
      patients showed a substantial reduction in proteinuria and resolution of
      hematuria within 5 months. A follow-up biopsy in two of the patients showed a
      substantial reduction in the severity of glomerular lesions and a decrease in the
      number of activated macrophages. In conclusion, Miz therapy was found to be a
      safe and effective therapy in three cases of steroid-resistant pediatric IgAN.
      The ability of Miz to reduce the number of activated macrophages may be an
      important mechanism by which this drug ameliorated renal disease in these
      patients.

PMID- 18038159
TI  - Reliability of different expert systems for profiling proteinuria in children
      with kidney diseases.
AB  - This study was designed to compare three urinary protein expert systems for
      profiling proteinuria in children with kidney diseases. Freshly voided urine
      specimens were collected from 61 children with glomerular diseases, 19 children
      with tubular diseases and 25 healthy children aged 3-16 years. The urinary
      protein expert systems were: (1) albumin/total protein ratio (APR), (2) alpha-1
      microglobulin/alpha-1-microglobulin + albumin algorithm (AAA), and (3) the
      complex urine protein expert system (UPES, PROTIS) algorithm. APR correctly
      identified glomerular proteinuria in 47/61 children, tubular proteinuria in 16/19
      children and normal proteinuria in 23/25 healthy children. AAA correctly
      identified glomerular proteinuria in 61/61 children and tubular proteinuria in
      18/19 children, and 25/25 healthy children were characterized as having no
      abnormal proteinuria. AAA was not influenced by the stage of chronic kidney
      disease. UPES differentiated the type of proteinuria in children with glomerular
      diseases into glomerular (50/61 patients) and mixed glomerulo-tubular (6/61
      patients). Tubular proteinuria was identified in 16/19 patients and described as
      mixed glomerulo-tubular proteinuria in 3/19 patients. Mixed glomerulo-tubular
      proteinuria was found only in children with chronic kidney disease stages 2-5 of
      glomerular and tubular diseases. In conclusion, the AAA and UPES had the highest
      accuracy levels.

PMID- 18038160
TI  - Limitation of activities of daily living accompanying reduced neck mobility after
      laminoplasty preserving or reattaching the semispinalis cervicis into axis.
AB  - Although difficulties with neck mobility often interfere with patients'
      activities of daily living (ADL) after cervical laminoplasty, there was no
      detailed study on the relation between the limitations of ADL accompanying
      postoperative reduced neck mobility and the cervical posterior approach. The aim
      of this study was to compare retrospectively the frequency of limitations of ADL
      accompanying neck mobility after laminoplasty preserving the semispinalis
      cervicis inserted into the C2 spinous process with that after laminoplasty
      reattaching the muscle to C2. Forty-nine patients after C4-C7 laminoplasty with
      C3 laminectomy preserving the semispinalis cervicis inserted into C2 (Group A)
      and 24 patients after C3-C7 laminoplasty reattaching the muscle (Group B) were
      evaluated. The frequency of postoperative limitations of ADL accompanying each of
      three neck movements of extension, flexion and rotation were investigated. The
      postoperative O-C7 angles at extension and flexion was measured on lateral
      extension and flexion radiographs of the cervical spine, respectively. The
      postoperative cervical range of motion in rotation was measured in the cranial
      view using a digital camera. Frequency of limitations of ADL accompanying
      extension was lower (P = 0.037) in Group A (2%) than in Group B (17%). Frequency
      of limitations of ADL accompanying flexion was similar in Group A (8%) and Group
      B (4%). Frequency of limitations of ADL accompanying rotation was lower (P =
      0.031) in Group A (12%) than in Group B (33%). Average O-C7 angle at extension
      was significantly larger (P = 0.002) in Group A (147 degrees ) than in Group B
      (136 degrees ). Average O-C7 angle at flexion was similar in Group A (93 degrees
      ) and Group B (91 degrees ). Average range of motion in rotation was
      significantly larger (P = 0.004) in Group A (110 degrees ) than in Group B (91
      degrees ). This retrospective study suggested that the frequency of limitations
      of ADL accompanying neck extension or rotation was lower after laminoplasty
      preserving the semispinalis cervicis inserted into C2 than after laminoplasty
      reattaching the muscle.

PMID- 18038162
TI  - Effect of steric molecular field settings on CoMFA predictivity.
AB  - Steric molecular field can be represented in a number of ways in comparative
      molecular field analysis (CoMFA). This study aimed to investigate whether the
      choice of steric molecular field settings significantly influences the predictive
      performance of CoMFA and, if so, which is the best. The three-dimensional
      quantitative structure activity relationship (3D-QSAR) models based on Lennard
      Jones, indicator, parabolic and Gaussian steric fields were compared using 28
      datasets taken from the literature. The analysis of the predictive ability of
      these models (cross validated R(2)) indicates that steric fields in which the
      value drops off quickly with distance (i.e. Lennard-Jones and indicator fields)
      tend to perform better than the Gaussian version, which has a slower and smoother
      decrease. Furthermore, depending on the steric field type used, the field
      sampling density (i.e. grid spacing) has a variable influence on the predictive
      ability of the models generated.

PMID- 18038163
TI  - Pattern recognition based on color-coded quantum mechanical surfaces for
      molecular alignment.
AB  - A pattern recognition algorithm for the alignment of drug-like molecules has been
      implemented. The method is based on the calculation of quantum mechanical derived
      local properties defined on a molecular surface. This approach has been shown to
      be very useful in attempting to derive generalized, non-atom based
      representations of molecular structure. The visualization of these surfaces is
      described together with details of the methodology developed for their use in
      molecular overlay and similarity calculations. In addition, this paper also
      introduces an additional local property, the local curvature (C (L)), which can
      be used together with the quantum mechanical properties to describe the local
      shape. The method is exemplified using some problems representing common tasks
      encountered in molecular similarity.

PMID- 18038161
TI  - Risk factors for back pain-related loss of working time after surgery for lumbar
      disc herniation: a 5-year follow-up study.
AB  - The aim of this study is to explore the occurrence and the risk factors of back
      related loss of working time in patients undergoing surgery for lumbar disc
      herniation. One hundred and fifty-two gainfully employed patients underwent
      surgery for lumbar disc herniation. Two months postoperatively, those patients
      completed a self-report questionnaire including queries on back and leg pain
      (VAS), functional capacity (Oswestry disability index--ODI, version 1.0), and
      motivation to work. After 5 years, lost working time was evaluated by means of a
      postal questionnaire about sick leave and disability pensions. The cumulative
      number of back pain-related days-off work was calculated for each patient. All
      152 patients, 86 men and 66 women, were prescribed sick leave for the first 2
      months. Thereafter, 80 (53%) of them reported back pain-related sick leave or
      early retirement. A permanent work disability pension due to back problems was
      awarded to 15 (10%) patients, 5 men (6%) and 10 women (15%). Median number of all
      work disability days per year was 11 (interquartile range [IQR] 9-37); it was 9
      days (IQR 9-22) in patients with minimal disability (ODI score 0-20) at 2 months
      postoperatively and 67 days (IQR 9-352) in those with moderate or severe
      disability (ODI > 20; P < 0.001). The respective means were 61, 29, and 140
      days/year. Multivariate analysis showed ODI > 20, leg pain, and poor motivation
      to work to be the risk factors for extension of work disability. Results of the
      present study show that after the lumbar disc surgery, poor outcome in
      questionnaire measures the physical functioning (ODI) and leg pain at 2 months
      postoperatively, as well as poor motivation to work, are associated with the loss
      of working time. Patients with unfavourable prognosis should be directed to
      rehabilitation before the loss of employment.

PMID- 18038165
TI  - Physical mapping in large genomes: accelerating anchoring of BAC contigs to
      genetic maps through in silico analysis.
AB  - Anchored physical maps represent essential frameworks for map-based cloning,
      comparative genomics studies, and genome sequencing projects. High throughput
      anchoring can be achieved by polymerase chain reaction (PCR) screening of
      bacterial artificial chromosome (BAC) library pools with molecular markers.
      However, for large genomes such as wheat, the development of high dimension pools
      and the number of reactions that need to be performed can be extremely large
      making the screening laborious and costly. To improve the cost efficiency of
      anchoring in such large genomes, we have developed a new software named Elephant
      (electronic physical map anchoring tool) that combines BAC contig information
      generated by FingerPrinted Contig with results of BAC library pools screening to
      identify BAC addresses with a minimal amount of PCR reactions. Elephant was
      evaluated during the construction of a physical map of chromosome 3B of hexaploid
      wheat. Results show that a one dimensional pool screening can be sufficient to
      anchor a BAC contig while reducing the number of PCR by 384-fold thereby
      demonstrating that Elephant is an efficient and cost-effective tool to support
      physical mapping in large genomes.

PMID- 18038166
TI  - Preferences and utilities for the symptoms of moderate to severe allergic asthma.
AB  - INTRODUCTION: Patients with moderate to severe allergic asthma have persistent
      poorly controlled asthma despite inhaled or systemic corticosteroid therapy. New
      therapies are becoming more widely available to treat such patients, but their
      value needs to be formally assessed in an economic evaluation. Within a publicly
      funded health care system such an analysis should reflect societal preferences
      when measuring treatment benefits. The aim of this study was to elicit societal
      preferences for the symptom burden associated with moderate to severe allergic
      asthma. METHOD: Existing daily symptom diary data from a clinical trial were used
      to develop health state descriptions for evaluation in a standard gamble
      interview. Five health states were produced that reflected five distinct levels
      of control ranging from 'complete control of asthma' to 'worsening of asthma', as
      defined by another outcome measure. The symptom diary data were also used as
      attributes in a discrete choice experiment (DCE) to estimate willingness to pay
      for improvements in symptoms. Members of the general public (n = 101) completed
      the interview. RESULTS: Thirteen participants failed the consistency checks and
      were excluded from the analysis. Societal utility ratings for the health states
      ranged from 0.71 (worsening of asthma) to 0.78 (complete control of asthma). The
      participants were also willing to pay 160 pounds a month for the avoidance of all
      symptoms. CONCLUSIONS: The range of utility values (0.71-0.78) demonstrates the
      severity of moderate to severe allergic asthma. However the spread of scores
      between complete control of asthma and worsening of asthma was lower than was
      expected. The community sample placed only a moderate value on the avoidance of
      all asthma symptoms in the DCE survey. The results suggest that the community
      sample may not have fully understood the benefits of control over asthma symptoms
      and the limitations such symptoms can impose on everyday life.

PMID- 18038167
TI  - The Nightingale Prize for the best scientific paper published in MBEC 2006.

PMID- 18038168
TI  - Imaging in unilateral Wilms tumour.
AB  - Wilms tumour is one of the most common malignancies in children, with an
      excellent prognosis after therapy. There is a very diverse approach to treatment
      according to geographical location. This variation in therapeutic attitude toward
      Wilms tumour, particularly between the United States and Europe, has consequences
      for the choice of imaging modality at diagnosis. In Europe, the International
      Society of Paediatric Oncology (SIOP) treatment protocol is based on chemotherapy
      followed by surgery. Imaging (US, CT and MRI), clinical history and examination
      will help predict whether the findings are consistent with Wilms tumour.
      Furthermore, in the UK preoperative image-guided biopsy is advised to help
      identify the small group of patients who, despite typical imaging features of
      Wilms tumour, have other types of neoplasia that require alternative management.
      In the United States, the National Wilms Tumor Study (NWTS) advises surgery prior
      to chemo- and radiotherapy. Hence imaging must provide detailed anatomical
      information for surgical planning. This article discusses the role of imaging at
      diagnosis and the relative strengths and weaknesses of the available radiological
      techniques. We also focus on imaging the lung for metastatic disease and the
      consequences (to the patient's ultimate outcome) of CT-diagnosed small pulmonary
      nodules and discuss the radiological diagnosis and consequences of tumour rupture
      present at diagnosis.

PMID- 18038169
TI  - MDCT assessment of tracheomalacia in symptomatic infants with mediastinal aortic
      vascular anomalies: preliminary technical experience.
AB  - BACKGROUND: Mediastinal aortic vascular anomalies are relatively common causes of
      extrinsic central airway narrowing in infants with respiratory symptoms. Surgical
      correction of mediastinal aortic vascular anomalies alone might not adequately
      treat airway symptoms if extrinsic narrowing is accompanied by intrinsic
      tracheomalacia (TM), a condition that escapes detection on routine end
      inspiratory imaging. Paired inspiratory-expiratory multidetector CT (MDCT) has
      the potential to facilitate early diagnosis and timely management of TM in
      symptomatic infants with mediastinal aortic vascular anomalies. OBJECTIVE: To
      assess the technical feasibility of paired inspiratory-expiratory MDCT for
      evaluating TM among symptomatic infants with mediastinal aortic vascular
      anomalies. MATERIALS AND METHODS: The study group consisted of five consecutive
      symptomatic infants (four male, one female; mean age 4.1 months, age range 2
      weeks to 6 months) with mediastinal aortic vascular anomalies who were referred
      for paired inspiratory-expiratory MDCT during a 22-month period. CT angiography
      was concurrently performed during the end-inspiration phase of the study. Two
      pediatric radiologists in consensus reviewed all CT images in a randomized and
      blinded fashion. The end-inspiration and end-expiration CT images were reviewed
      for the presence and severity of tracheal narrowing. TM was defined as > or =50%
      reduction in tracheal cross-sectional luminal area between end-inspiration and
      end-expiration. The presence of TM was compared to the bronchoscopy results when
      available (n = 4). RESULTS: Paired inspiratory-expiratory MDCT was technically
      successful in all five patients. Mediastinal aortic vascular anomalies included a
      right aortic arch with an aberrant left subclavian artery (n = 2), innominate
      artery compression (n = 2), and a left aortic arch with an aberrant right
      subclavian artery (n = 1). Three (60%) of the five patients demonstrated focal TM
      at the level of mediastinal aortic vascular anomalies. The CT results were
      concordant with the results of bronchoscopy in all patients who underwent
      bronchoscopy (n = 4). CONCLUSION: Paired inspiratory-expiratory MDCT is
      technically feasible for evaluating TM in symptomatic infants with mediastinal
      aortic vascular anomalies and has the potential to facilitate prompt diagnosis
      and treatment.

PMID- 18038172
TI  - Frontiers in parasite neurobiology: parasite genomics, neural signalling and new
      targets for control.

PMID- 18038173
TI  - Prevalence of depressive symptoms in university students from Germany, Denmark,
      Poland and Bulgaria.
AB  - BACKGROUND: Previous research indicated a higher prevalence of depressive
      symptoms among students from Eastern European countries than students from
      Western European countries. This difference was thought to be linked to political
      and economic instabilities resulting from political changes in the early 1990s.
      We investigated whether these differences persist 15 years later. METHODS: Using
      data from a general health survey among first year students (N = 2,651) from two
      Western (Germany and Denmark) and two Eastern European countries (Poland and
      Bulgaria), our analysis was restricted to 2,146 students below 23 years of age.
      Depressive symptoms were measured using the Modified Beck Depression Inventory (M
      BDI). The recommended cut-off point of the M-BDI for depression screening in the
      general population is a score of > or =35. Perceived income sufficiency was
      measured on a four-point scale from "totally sufficient" to "not sufficient at
      all". Analysis of variance and logistic regression were performed to assess the
      differences in depressive symptoms between countries adjusting for income
      sufficiency. RESULTS: Depressive symptoms were more prevalent in Eastern European
      than Western European countries (M-BDI scores of > or =35 in Germany 26.7%/22.8%,
      in Denmark 24.9%/12.1%, in Poland 45.5%/27.3%, in Bulgaria 42.9%/33.8% for female
      and male students, respectively). There was an association between income
      perceived as insufficient and higher levels of depressive symptoms, but it did
      not differ across the countries. Adjusting for perceived income sufficiency had
      little effect on differences in the prevalence of depressive symptoms across
      countries. CONCLUSIONS: The difference in prevalence of depressive symptoms in
      university students from Eastern and Western European countries persists 15 years
      after political changes have taken place and cannot be explained by differences
      in perceived sufficiency of income.

PMID- 18038174
TI  - Novel mutation in the SPAST gene in a patient with spastic paraparesis.

PMID- 18038178
TI  - Transdermal fentanyl improves pain control and functionality in patients with
      osteoarthritis: an open-label Canadian trial.
AB  - Current treatment guidelines advocate opioids for arthritis when standard
      analgesics produce inadequate relief. Efficacy, adverse effects (AEs), dosing
      regimens, physician expertise and patient preference influence treatment
      selection. This study assessed transdermal fentanyl (TDF) as a treatment option
      for osteoarthritis (OA) patients. This prospective, Canadian open-label, 8-week
      trial assessed the efficacy and safety of TDF in patients with OA of hip or knee
      with moderate-to-severe target joint pain inadequately controlled using weak
      opioids. TDF was initiated at 25 mcg/h and titrated to optimal pain control.
      Rescue acetaminophen 500 mg was allowed (maximum 4 g/day). The main endpoint was
      improvement in pain control assessment rating (five rating categories); pain
      intensity (0-10 numerical scale), functionality (WOMAC-OA Index), health-related
      quality of life (SF-36 Health Survey) and global impression were also evaluated.
      Eighty-one patients (61% female, mean age 60 years) were enrolled; 62 were
      evaluable. All had failed on previous weak opioid therapy, primarily codeine or
      codeine combinations. At treatment end, 65% rated pain control as improved (Pain
      Control Assessment rating change >or=1 category; p<0.0001); mean change in pain
      intensity was a reduction of greater than 2 (p<0.0001); almost 50% were
      maintained on TDF 25 mcg/h with less than 1.3 g/day of rescue acetaminophen. At 1
      month and end of treatment, changes in the SF-36 physical global scale and
      individual sub-scores for the pain index and role-physical scales were highly
      significant (p<0.0001). Improvement in functionality was noted at 1 month and at
      end of treatment with significant reductions in total WOMAC score, individual
      pain, stiffness and physical function sub-scores (p<0.0001). AEs causing
      discontinuation (n=32) included nausea, dizziness and vomiting. Most treatment
      related AEs were mild to moderate in intensity. TDF improved pain control,
      functionality and health-related quality of life in these patients. The findings
      support current recommendations for use of opioids such as TDF as a treatment
      option for a sub-population of patients with OA pain.

PMID- 18038179
TI  - Within-patient right-left blinded comparison of diode (810 nm) laser therapy and
      intense pulsed light therapy for hair removal.
AB  - Excessive facial hair in women can cause significant psychological distress. A
      variety of treatment methods are available, including lasers and, more recently,
      intense pulsed light (IPL) sources. There are very few studies comparing laser
      and IPL devices. The purpose of our study was to compare a laser diode device
      with an IPL, using a within-patient, right-left, assessor-blinded, controlled,
      study design. Hair counts were made, using coded close-up photographs. Treatments
      were carried out on three occasions at 6-week intervals, and a final assessment
      was made 6 weeks following the third treatment. Patient self-assessment was also
      included. Nine women were recruited, and seven completed the study. Average hair
      counts in a 16 cm(2) area before and after treatment were, respectively, 42.4 and
      10.4 (laser), 38.1 and 20.4 (IPL), 45.3 and 44.7 (control). Both laser and IPL
      reduced the hair count substantially; laser vs control was significant at
      P=0.028, but IPL vs control had P=0.13, suggesting that more subjects or more
      treatments were required if statistical significance were to be achieved. Despite
      subjecting the patients to higher pain scores and more inflammation, laser was
      preferred by five patients; two preferred IPL and one had no preference.

PMID- 18038180
TI  - Comparison of microleakages of photo-cured composites using three different light
      sources: halogen lamp, LED and argon laser: an in vitro study.
AB  - In this study, we compared the microleakage of composite fillings cured with
      halogen bulb, LED and argon ion laser (488 nm). Twenty-four extracted human
      molars were divided randomly in three groups. Six cavities were prepared on the
      coronal part of each tooth. Standard cavities (1.7 x 2 mm) were prepared.
      Cavities were acid etched, sealed with Scotch Bond 1 and filled by a hybrid
      composite. Cavities were exposed to one light source, thermocycled and immersed
      in a 2% methylene blue dye solution. Dye penetration in the leakage of cavities
      was recorded using a digital optical microscope. Mean values of percentage of dye
      penetrations in microleakages of cavities were 49.303 +/- 5.178% for cavities
      cured with LED, 44.486 +/- 6.075% with halogen bulb and 36.647 +/- 5.936% for
      those cured by argon laser. Statistically significant difference exists between
      cavities cured by halogen vs LED (P < 0.01), halogen vs laser (P < 0.001) and LED
      vs laser (P < 0.001). The lowest microleakage was observed in the cavities and
      composites cured with argon ion laser.

PMID- 18038181
TI  - The role of endorectal ultrasound in therapeutic decision-making for local vs.
      transabdominal resection of rectal tumors.
AB  - INTRODUCTION: In rectal tumors, preoperative biopsies frequently fail to diagnose
      an invasive carcinoma. Endorectal ultrasound is considered a useful adjunct in
      preoperative staging of rectal tumors. However, feasibility of endorectal
      ultrasound and its role in therapeutic decision-making in presumed rectal
      adenomas is sparsely studied. METHODS: Endorectal ultrasound was performed in 268
      tumors referred for local excision because biopsies showed tubulovillous adenoma.
      Feasibility of endorectal ultrasound was studied and ultrasound staging was
      compared with definite histopathologic findings. RESULTS: In 231 tumors,
      endorectal ultrasound was technically feasible (86 percent). Median distance from
      the dentate line was 11 cm in nonassessable tumors and 7 cm in assessable tumors
      (P < 0.001). In 21 tumors, endorectal ultrasound was not conclusive, mainly in
      tumors being recurrent or after recent endoscopic manipulation (P < 0.001). With
      endorectal ultrasound the rate of preoperative missed carcinomas could be reduced
      from 21 to 3 percent (P < 0.01). In diagnosing tubulovillous adenomas,
      sensitivity and specificity of endorectal ultrasound was 89 and 86 percent,
      respectively. CONCLUSIONS: Endorectal ultrasound is technically feasible in
      almost all presumed rectal adenomas, referred for local excision. Proper
      endorectal ultrasound interpretation is possible in 78 percent of all presumed
      rectal adenomas. Endorectal ultrasound is very reliable in diagnosing
      tubulovillous adenomas, and therapeutic decision-making regarding local excision
      vs. radical surgery based on endorectal ultrasound is valid.

PMID- 18038182
TI  - Divergent abdominal bristle patterns in two distantly related drosophilids:
      antero-posterior variations and sexual dimorphism in a modular trait.
AB  - The number of neurosensory bristles on abdominal sternites of Drosophila is a
      most investigated trait for quantitative genetic studies. However, the
      developmental pattern expressed on successive segments in both sexes has remained
      so far a neglected field. We explored three aspects of this general problem with
      an isofemale line design: comparing two distantly related species, Drosophila
      melanogaster and Zaprionus indianus, investigating bristle number variation along
      the antero-posterior axis, and analysing the sexual dimorphism. Antero-posterior
      variations could be analysed from segment A2 to A7 in females, and A2-A5 in
      males. In D. melanogaster, males and females showed parallel changes with a
      consistently lower number in males. In Z. indianus females the number was quite
      stable along the abdomen, while in males an important antero-posterior increase
      was found. The sexual dimorphism was further analysed by considering the female
      male correlation and the female/male ratio. The results suggest that sternite
      bristle number is determined by several developmental genetic systems. One is
      acting along the antero-posterior axis and may be associated to a gradient, since
      the genetic correlation decreases when more distant segments are compared.
      Another is acting in the same way on most segments of both sexes, since the
      female-male genetic correlation is similar between homologous and non-homologous
      segments. Finally, genes with specific sex effects are acting on A7 in females of
      both species, and on A5 in Z. indianus males. The overall architecture of female
      and male abdomen seems to be constrained by the development of reproductive
      organs. A large difference between species suggests, however, that the sexual
      dimorphism of abdominal bristle number is not evolutionarily constrained.

PMID- 18038183
TI  - Mapping of rRNA genes and telomeric sequences in Danube salmon (Hucho hucho)
      chromosomes using primed in situ labeling technique (PRINS).
AB  - In the current paper we described the application of primed in situ (PRINS)
      labeling approach for the chromosomal mapping of repetitive DNA sequences in
      Danube salmon (Hucho hucho) (2n = 82, NF = 112). PRINS was successfully performed
      with primers enabling amplification of 5S rRNA genes (minor rDNAs), NOR building
      DNA sequences (major rDNAs), and telomeric sequences. Two loci of 5S rRNA were
      observed on distinct chromosome pairs; the minor arrays were located
      interstitially on the long (q) arms of two large metacentrics (chromosomes No. 3)
      and the large clusters of 5S rDNAs were assigned to the short (p) arms of two
      subtelocentric chromosomes No. 18. Major rDNA clusters were observed on the p
      arms of two submeta-subtelocentric chromosomes No. 10. These chromosomal areas
      were built with GC-rich chromatin what was proved in the course of chromomycin
      A(3) (CMA(3)) staining performed sequentially. Major and minor rDNA families were
      not co-localized in the Danube salmon chromosomes. The distinct hybridization
      signals at the ends of all the chromosomes were provided in the course of PRINS
      with (CCCTAA)(n) primer. The chromosomal localization of rRNA genes and telomeric
      DNA sequences was discussed in the context of Salmonidae karyotype evolution.

PMID- 18038184
TI  - The impact of a clinical information system in an intensive care unit.
AB  - PURPOSE: Although clinical information systems (CISs) have been available and
      implemented in many Intensive care Units (ICUs) for more than a decade, there is
      little objective evidence of their impact on the quality of care and staff
      perceptions. This study was performed to compare time spent charting with pen and
      paper patient data versus time spent with the new electronic CIS and to evaluate
      staff perceptions of a CIS in an ICU. MATERIALS AND METHODS: Time spent every day
      was calculated for each patient, for 7 days, for recording on the paper vital
      signs and physician therapeutic orders and time spent for computing fluid balance
      and scores. This time was then compared with time required to make the same
      activities by means of CIS, 10 months after its introduction in ICU. Four years
      after the installation of CIS, a questionnaire was given to all staff attending
      to the ICU to evaluate their opinions of the CIS. RESULTS: The CIS took less
      staff time to record common ICU data than paper records (3 +/- 2 minutes/day
      versus 37 +/- 7 minutes/day respectively, P< 0.001). Perceptions of the CIS were
      that computers promoted an improving charting quality. CONCLUSIONS: The
      implementation of a CIS was associated with a reduced time spent for daily
      activity and a positive medical and nursing staff perception.

PMID- 18038185
TI  - The use of comet assay in measuring DNA damage and repair efficiency in child,
      adult, and old age populations.
AB  - In the present study, we used the Comet assay to estimate basal DNA damage in
      three distinct populations aged 5-10, 40-50, and 60-70 years old. The DNA damage
      induced by hydrogen peroxide and gamma-irradiation in the lymphocytes of these
      populations, as well as their repair activity, was also studied. Finally, we
      measured apoptosis and necrosis after the effect of these agents. Our results
      indicate that the older population (60-70 years old) showed higher basal levels
      of DNA damage and was more sensitive to the effects of the DNA-damaging agents
      than the adult one (40-50 years old), who, in turn, was more sensitive than the
      younger population (5-10 years old). A decline of the repair efficiency with age
      to the DNA damage induced by the two agents was also observed. Apoptosis and
      necrosis were also affected by age.

PMID- 18038186
TI  - Colorectal cancer screening among Latinos from U.S. cities along the Texas-Mexico
      border.
AB  - Colorectal cancer (CRC) screening rates are comparatively low for U.S. Hispanics.
      To learn more about the factors influencing CRC screening among Hispanics living
      along the U.S.-Mexico border, 12 focus groups were conducted with Hispanic men
      and women aged 50 years and older in three Texas counties; Cameron County
      (Brownsville), Webb County (Laredo), and El Paso County, (El Paso). The focus
      group guide contained questions about health care behavior, knowledge about CRC,
      experiences with cancer, and factors that influence CRC screening. A total of 92
      individuals participated with the majority aged 50-69 (75%). Twenty percent were
      born in the United States and 51% had lived in the United States for more than 20
      years. Participants had low levels of education, income, and insurance coverage.
      The analysis revealed several overarching and contextual themes relating to
      knowledge, attitudes, beliefs, and emotions about cancer and CRC screening. A
      prevalent theme that emerged from all groups was frustration and a lack of
      confidence in the U.S. healthcare system. Few participants had been advised by
      their providers to obtain CRC screening. Lack of patient knowledge about
      colorectal cancer and screening appeared to be a critical factor influencing
      screening. Themes about death and pain due to cancer were prevalent as were
      cultural factors such as machismo and embarrassment. System level barriers such
      as cost, medical insurance and transportation also impacted screening. These
      findings suggest that strategies are needed to educate Hispanic residents of
      border communities about CRC and to motivate them to undergo CRC screening.

PMID- 18038187
TI  - Joint effect between regular use of non-steroidal anti-inflammatory drugs,
      variants in inflammatory genes and risk of lymphoma.
AB  - OBJECTIVE: Limited evidence suggests the importance of inflammatory processes for
      the etiology of lymphomas. To further research in this area, we investigated the
      role of genetic variants in key inflammatory factors, non-steroidal anti
      inflammatory drug [NSAID] use, and their joint effect in lymphomagenesis.
      METHODS: The study comprised 710 case-control pairs, matched for gender, age, and
      study region. We examined the association of regular NSAID use and polymorphisms
      in prostaglandin-endoperoxide synthase-2 (COX2), prostaglandin E synthase
      (PTGES), interleukin-1 alpha (IL1A), IL-1 beta (IL1B), and IL-1 receptor
      antagonist (IL1RA), and lymphoma risk by applying logistic regression to
      calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS:
      Regular NSAID use was associated with a slightly reduced risk of B-NHL (OR = 0.8,
      95% CI = 0.6-1.1). For T-NHL, the COX2 rs2745557 A-allele conferred a 2.2-fold
      (95% CI = 1.1-4.5) and homozygosis for the IL1RN rs454078 T-allele was associated
      with a 4.5-fold (95% CI = 1.4-13.9) elevated risk, however, based on sparse data.
      IL1 haplotype 5 was associated with a statistically significant 43% increased
      risk for B-NHL among non-regular users of NSAIDs, but a 70% decreased risk for
      regular users (p-value for interaction < 0.001). CONCLUSIONS: These results
      suggest the relevance of joint effects between NSAID use and IL1 haplotypes on
      the risk of B-NHL.

PMID- 18038188
TI  - Lack of interaction between sensing-intuitive learning styles and problem-first
      versus information-first instruction: a randomized crossover trial.
AB  - BACKGROUND: Adaptation to learning styles has been proposed to enhance learning.
      OBJECTIVE: We hypothesized that learners with sensing learning style would
      perform better using a problem-first instructional method while intuitive
      learners would do better using an information-first method. DESIGN: Randomized,
      controlled, crossover trial. SETTING: Resident ambulatory clinics. PARTICIPANTS:
      123 internal medicine residents. INTERVENTIONS: Four Web-based modules in
      ambulatory internal medicine were developed in both "didactic" (information
      first, followed by patient problem and questions) and "problem" (case and
      questions first, followed by information) format. MEASUREMENTS: Knowledge
      posttest, format preference, learning style (Index of Learning Styles). RESULTS:
      Knowledge scores were similar between the didactic (mean +/- standard error, 83.0
      +/- 0.8) and problem (82.3 +/- 0.8) formats (p = .42; 95% confidence interval
      [CI] for difference, -2.3 to 0.9). There was no difference between formats in
      regression slopes of knowledge scores on sensing-intuitive scores (p = .63) or in
      analysis of knowledge scores by styles classification (sensing 82.5 +/- 1.0,
      intermediate 83.7 +/- 1.2, intuitive 81.0 +/- 1.5; p = .37 for main effect, p =
      .59 for interaction with format). Format preference was neutral (3.2 +/- 0.2 [1
      strongly prefers didactic, 6 strongly prefers problem], p = .12), and there was
      no association between learning styles and preference (p = .44). Formats were
      similar in time to complete modules (43.7 +/- 2.2 vs 43.2 +/- 2.2 minutes, p =
      .72). CONCLUSIONS: Starting instruction with a problem (versus employing problems
      later on) may not improve learning outcomes. Sensing and intuitive learners
      perform similarly following problem-first and didactic-first instruction. Results
      may apply to other instructional media.

PMID- 18038190
TI  - Calcium scoring using 64-slice MDCT, dual source CT and EBT: a comparative
      phantom study.
AB  - PURPOSE: Assessment of calcium scoring (Ca-scoring) on a 64-slice multi-detector
      computed tomography (MDCT) scanner, a dual-source computed tomography (DSCT)
      scanner and an electron beam tomography (EBT) scanner with a moving cardiac
      phantom as a function of heart rate, slice thickness and calcium density. METHODS
      AND MATERIALS: Three artificial arteries with inserted calcifications of
      different sizes and densities were scanned at rest (0 beats per minute) and at 50
      110 beats per minute (bpm) with an interval of 10 bpm using 64-slice MDCT, DSCT
      and EBT. Images were reconstructed with a slice thickness of 0.6 and 3.0 mm.
      Agatston score, volume score and equivalent mass score were determined for each
      artery. A cardiac motion susceptibility (CMS) index was introduced to assess the
      susceptibility of Ca-scoring to heart rate. In addition, a difference (Delta)
      index was introduced to assess the difference of absolute Ca-scoring on MDCT and
      DSCT with EBT. RESULTS: Ca-score is relatively constant up to 60 bpm and starts
      to decrease or increase above 70 bpm, depending on scoring method, calcification
      density and slice thickness. EBT showed the least susceptibility to cardiac
      motion with the smallest average CMS-index (2.5). The average CMS-index of 64
      slice MDCT (9.0) is approximately 2.5 times the average CMS-index of DSCT (3.6).
      The use of a smaller slice thickness decreases the CMS-index for both CT
      modalities. The Delta-index for DSCT at 0.6 mm (53.2) is approximately 30% lower
      than the Delta-index for 64-slice MDCT at 0.6 mm (72.0). The Delta-indexes at 3.0
      mm are approximately equal for both modalities (96.9 and 102.0 for 64-slice MDCT
      and DSCT respectively). CONCLUSION: Ca-scoring is influenced by heart rate, slice
      thickness and modality used. Ca-scoring on DSCT is approximately 50% less
      susceptible to cardiac motion as 64-slice MDCT. DSCT offers a better
      approximation of absolute calcium score on EBT than 64-slice MDCT when using a
      smaller slice thickness. A smaller slice thickness reduces the susceptibility to
      cardiac motion and reduces the difference between CT-data and EBT-data. The best
      approximation of EBT on CT is found for DSCT with a slice thickness of 0.6 mm.

PMID- 18038192
TI  - Development of an alternative approach to protein crystallization.
AB  - We are developing an alternate strategy for the crystallization of macromolecules
      that does not, like current methods, depend on the optimization of traditional
      variables such as pH and precipitant concentration, but is based on the
      hypothesis that many conventional small molecules might establish stabilizing,
      intermolecular, non covalent crosslinks in crystals, and thereby promote lattice
      formation. To test the hypothesis, we carried out preliminary experiments
      encompassing 18,240 crystallization trials using 81 different proteins, and 200
      chemical compounds. Statistical analysis of the results demonstrated the validity
      of the idea. In addition, we conducted X-ray diffraction analyses of some of the
      crystals grown in the experiments. These clearly showed incorporation of
      conventional molecules into the protein crystal lattices, and further validated
      the underlying hypothesis. We are currently extending the investigations to
      include a broader and more diverse set of proteins, an expanded search of
      conventional and biologically active small molecules, and a wider range of
      precipitants. The strategy proposed here is essentially orthogonal to current
      approaches and has an objective of doubling the success rate of today.

PMID- 18038189
TI  - Neurological implications of urea cycle disorders.
AB  - The urea cycle disorders constitute a group of rare congenital disorders caused
      by a deficiency of the enzymes or transport proteins required to remove ammonia
      from the body. Via a series of biochemical steps, nitrogen, the waste product of
      protein metabolism, is removed from the blood and converted into urea. A
      consequence of these disorders is hyperammonaemia, resulting in central nervous
      system dysfunction with mental status changes, brain oedema, seizures, coma, and
      potentially death. Both acute and chronic hyperammonaemia result in alterations
      of neurotransmitter systems. In acute hyperammonaemia, activation of the NMDA
      receptor leads to excitotoxic cell death, changes in energy metabolism and
      alterations in protein expression of the astrocyte that affect volume regulation
      and contribute to oedema. Neuropathological evaluation demonstrates alterations
      in the astrocyte morphology. Imaging studies, in particular (1)H MRS, can reveal
      markers of impaired metabolism such as elevations of glutamine and reduction of
      myoinositol. In contrast, chronic hyperammonaemia leads to adaptive responses in
      the NMDA receptor and impairments in the glutamate-nitric oxide-cGMP pathway,
      leading to alterations in cognition and learning. Therapy of acute
      hyperammonaemia has relied on ammonia-lowering agents but in recent years there
      has been considerable interest in neuroprotective strategies. Recent studies have
      suggested restoration of learning abilities by pharmacological manipulation of
      brain cGMP with phosphodiesterase inhibitors. Thus, both strategies are
      intriguing areas for potential investigation in human urea cycle disorders.

PMID- 18038191
TI  - Cloning and functional identification of two members of the ZIP (Zrt, Irt-like
      protein) gene family in rice (Oryza sativa L.).
AB  - Two ZIP (Zrt, Irt-like Protein) cDNAs were isolated from rice (Oryza sativa L.)
      by RT-PCR approach, and named as OsZIP7a and OsZIP8 respectively. The predicted
      proteins of OsZIP7a and OsZIP8 consist of 384 and 390 amino acid residues
      respectively, and display high similarity to other plant ZIP proteins. Each
      protein contains eight transmembrane (TM) domains and a highly conserved ZIP
      signature motif, with a histidine-rich region in the variable region between TM
      domains III and IV. By semi-quantitative RT-PCR approach, it was found that the
      expression of OsZIP7a was significantly induced in rice roots by iron-deficiency,
      while that of OsZIP8 induced in both rice roots and shoots by zinc-deficiency.
      When expressed in yeast cells, OsZIP7a and OsZIP8 could complement an iron-uptake
      deficient yeast mutant and a zinc-uptake-deficient yeast mutant respectively. It
      suggested that the OsZIP7a and OsZIP8 might encode an iron and a zinc transporter
      protein in rice respectively.

PMID- 18038193
TI  - A quantitative polymerase chain reaction assay for detecting and identifying
      fungal contamination in human allograft tissue.
AB  - To complement donor selection and tissue processing, rapid and reliable
      detection, discrimination, and quantification of fungal pathogens are extremely
      important for tissues destined to be implanted into humans. The current detection
      method for fungal pathogens, in particular, is difficult and time-consuming.
      Quantitative polymerase chain reaction (qPCR) technology is considered one of the
      most sensitive methods to detect low levels of DNA. Here a qPCR method is
      described that can detect clinically relevant, pathogenic fungal organisms. The
      assay allowed the quantification of fungal organisms within a tissue implant and
      provides a means to identify the contaminating species. The primers for the qPCR
      assay were designed to amplify a conserved region of the L2 region of the large
      ribosomal subunit (LSU) gene. This set of primers was able to detect fewer than
      10 colony forming units from Aspergillus and Candida species in spiked samples.
      Clinical samples were also evaluated using this method and the data compared
      positively to the existing accepted 28-day fungal culture method for fungal
      detection. The qPCR method described herein significantly reduced the time
      required to identify fungal contamination in tissue implants.

PMID- 18038195
TI  - Is diversity good? Six possible conceptions of diversity and six possible
      answers.
AB  - Prominent ethical and policy issues such as affirmative action and female
      enrollment in science and engineering revolve around the idea that diversity is
      good. However, a precise definition is seldom provided. I show that diversity may
      be construed as a factual description, a craving for symmetry, an intrinsic good,
      an instrumental good, a symptom, or a side effect. These acceptions differ vastly
      in their nature and properties. Some are deeply mistaken and some others cannot
      lead to concrete policies. It is thus necessary to clarify what one means by
      'diversity.' It may be a neutral description of a given state; but this is
      insufficient to act. The idea that there should be the same representation in a
      specific context as in the overall population is both puzzling and arbitrary.
      Diversity as intrinsic good is a mere opinion, which cannot be concretely
      applied; moreover, the most commonly invoked forms of diversity (sexual and
      racial) are not intrinsically good. On the other hand, diversity as instrumental
      good can be evaluated empirically and can give rise to policies, but these may be
      very weak. Finally, symptoms and side effects are not actually about diversity. I
      consider the example of female enrollment in science and engineering,
      interpreting the various arguments found in the literature in light of this
      polysemy.

PMID- 18038196
TI  - Redescriptions of species of Tetrarhynchobothrium Diesing, 1850 and
      Didymorhynchus Beveridge & Campbell, 1988 (Cestoda: Trypanorhyncha), with the
      description of Zygorhynchus borneensis n. sp.
AB  - Tetrarhynchobothrium tenuicolle Diesing, 1850 is redescribed from the type
      specimens collected from Raja clavata Linnaeus in the Adriatic Sea. T. striatum
      (Wagener, 1854) is redescribed from voucher specimens from the type host,
      Myliobatis aquila Linnaeus, from the type-locality, off Naples, Italy. The two
      species are very similar in tentacular armature, but are provisionally maintained
      as independent species, since the armature of T. tenuicolle cannot be fully
      described and because all available specimens of T. striatum are immature,
      limiting comparisons of potential differences in segment anatomy. T. setiense
      Dollfus, 1969 is treated as a synonym of T. striatum. Zygorhynchus borneensis n.
      sp. is described from Himantura uarnacoides (Bleeker) and H. pastinacoides
      (Bleeker) off Sabah, Malaysia. The new species is distinguished from its
      congeners by the very small hooks present in the basal region and by the presence
      of a uterine pore. The metabasal tentacular armature of Didymorhynchus southwelli
      Beveridge & Campbell, 1988, described for the first time, is homeoacanthous and
      homeomorphous in form. However, it has a basal swelling with hook rows
      originating on the bothrial surface and terminating on the antibothrial surface
      of the tentacle.

PMID- 18038194
TI  - Causal factors implicated in research misconduct: evidence from ORI case files.
AB  - There has been relatively little empirical research into the causes of research
      misconduct. To begin to address this void, the authors collected data from closed
      case files of the Office of Research Integrity (ORI). These data were in the form
      of statements extracted from ORI file documents including transcripts,
      investigative reports, witness statements, and correspondence. Researchers
      assigned these statements to 44 different concepts. These concepts were then
      analyzed using multidimensional scaling and cluster analysis. The authors chose a
      solution consisting of seven clusters: (1) personal and professional stressors,
      (2) organizational climate, (3) job insecurities, (4) rationalizations A, (5)
      personal inhibitions, (6) rationalizations B and, (7) personality factors. The
      authors discuss the implications of their findings for policy and for future
      research.

PMID- 18038197
TI  - A new genus and species of mesoparasitic ergasilid (Copepoda: Cyclopoida) from
      brackish water pufferfishes collected in northern Australian waters.
AB  - A new mesoparasitic ergasilid copepod, Majalincola buthi n. g., n. sp., is
      described based on material collected from the gills of Marilyna darwinii
      (Castelnau) and M. meraukensis (de Beaufort) (Tetraodontidae) captured in
      brackish waters in northern Australia. The new genus is characterised by the
      presence in the fully-transformed adult female of: four tagmata (antennary, neck,
      postantennary cephalothoracic region and trunk region); a 5-segmented antennule;
      a trimerous leg 1 endopod; and a free exopod segment armed with two setae on the
      fifth leg. The establishment of the new genus is supported by the results of a
      cladistic analysis of Majalincola and members of its sister taxon.

PMID- 18038198
TI  - Contracaecum bioccai n. sp. from the brown pelican Pelecanus occidentalis (L.) in
      Colombia (Nematoda: Anisakidae): morphology, molecular evidence and its genetic
      relationship with congeners from fish-eating birds.
AB  - Contracaecum bioccai n. sp. is described from the brown pelican Pelecanus
      occidentalis (L.) in northern Colombia (Totumo Marsh) based on 20 enzyme loci
      studied using multilocus allozyme electrophoresis. Moreover, genetic
      relationships between the new taxon and related congeners are presented based on
      allozyme data-sets and sequence analyses (519 bp) of the mtDNA-cox2 gene. Fixed
      allele differences were found at some of the allozyme loci analysed in comparison
      with other Contracaecum spp. from pelicans and cormorants [i.e. the sibling
      species of the C. rudolphii Hartwich, 1964 complex, C. septentrionale Kreis,
      1955, C. micropapillatum (Stossich, 1890), C. microcephalum (Rudolphi, 1809) and
      C. pelagicum Johnston & Mawson, 1942]. The genetic distance, at the allozyme
      level, between C. bioccai n. sp. and its congeners ranged from D ( Nei ) = 0.80
      versus C. septentrionale to D ( Nei ) = 1.40 versus C. micropapillatum. The
      genetic distance at the mtDNA cox-2 level ranged, on average, from K-2P = 0.12
      versus the C. rudolphii species complex to K-2P = 0.15 versus C. micropapillatum.
      An overall concordant tree topology, obtained from UPGMA and NJ tree analyses
      inferred from allozyme data, as well as from MP, UPGMA and NJ inferred from mtDNA
      cox2 sequence analysis, showed C. bioccai n. sp. as a separated lineage to the
      other Contracaecum spp. A concordant result was also obtained by PCA analysis
      based on both the allozyme and mtDNA cox-2 data-sets. All of the tree topologies,
      derived from the phylogenetic analysis inferred from both allozymes and mtDNA
      data-sets, were in substantial agreement and depicted C. bioccai as closely
      related to the sibling species of the C. rudolphii complex (C. rudolphii A and C.
      rudolphii B) and C. septentrionale. Morphological analysis and a differential
      diagnosis based on male specimens of C. bioccai, which had been genetically
      characterised by both allozyme markers and mtDNA sequences analysis with respect
      to morphologically related congeners, enabled the detection of differences in a
      numbers of characters, including spicule length, the morphology of the distal end
      of the spicule and the distribution patterns of the distal caudal papillae.

PMID- 18038200
TI  - Redescription of Amblyomma varium Koch, 1844 (Acari: Ixodidae) based on light and
      scanning electron microscopy.
AB  - Amblyomma varium Koch, 1844 is a Neotropical tick, known as the 'sloth's giant
      tick', with records from southern Central America to Argentina. It is found
      almost exclusively on mammals of the families Bradypodidae and Magalonychidae
      (Xenarthra). Differences exist in discussions with regard to the dentition of the
      female hypostome being either 3/3 or 4/4. The male was also originally described
      as having a short spur on coxa IV, but some specimens recently collected from
      different Brazilian localities have this spur three times longer. These
      differences beg the question of whether there is more than one species included
      under this taxon. In order to answer this question and to clarify the taxonomic
      characters of this species, 258 adult specimens were examined, and a
      redescription of male and female based on light and scanning electron microscopy
      is provided. In addition, DNA was extracted from males with either a long or a
      short spur on coxa IV to help settle this question for future investigations on
      their taxonomy. The morphological study showed that the dental formula pattern
      for males and females is 3/3 and 4/4, respectively. When sequenced, the 12 S rDNA
      genes of both A. varium males with long and short spurs on coxa IV were found to
      be identical, indicating that the length of the spurs on coxa IV is likely to be
      an intraspecifically polymorphic character of this species.

PMID- 18038199
TI  - Molecular faunistics of accidental infections of Gyrodactylus Nordmann, 1832
      (Monogenea) parasitic on salmon Salmo salar L. and brown trout Salmo trutta L. in
      NW Russia.
AB  - Salmon Salmo salar L. and brown trout S. trutta L. juveniles were examined for
      the presence of accidental monogenean ectoparasitic species of Gyrodactylus
      Nordmann, 1832 in the Baltic and White Sea basins of Russian Karelia in order to
      estimate the frequency of host-switching attempts on an ecological timescale. To
      collect phylogeographical information and for exact species identification, the
      parasites were characterised by nuclear internal transcribed spacer sequences of
      rDNA (ITS) and, for some species, also by their mitochondrial DNA (CO1 gene)
      sequences. Four accidental Gyrodactylus species were observed on salmon and brown
      trout. A few specimens of G. aphyae Malmberg, 1957, the normal host of which is
      the Eurasian minnow Phoxinus phoxinus (L.), were observed on lake salmon from the
      Rivers Kurzhma (Lake Kuito, White Sea basin) and Vidlitsa (Lake Ladoga, Baltic
      basin). G. lucii Kulakovskaya, 1952, a parasite of the northern pike Esox lucius
      L., was observed on salmon in the Kurzhma. In the River Vidlitsa, two specimens
      of G. papernai Ergens & Bychowsky, 1967, normally on stone loach Barbatula
      barbatula (L.), were found on salmon. On anadromous White Sea salmon in the River
      Pulonga in Chupa Bay, a few salmon parr carried small colonies of G. arcuatus
      Bychowsky, 1933, which were shown to have originated from the local three-spined
      stickleback Gasterosteus aculeatus L. consumed as prey. No specimens of
      Gyrodactylus salaris Malmberg, 1957 were observed, although the Pulonga is the
      nearest salmon spawning river to the River Keret', which is heavily infected with
      introduced G. salaris. In the River Satulinoja, Lake Ladoga, three specimens of
      G. lotae Gusev, 1953, from burbot Lota lota (L.), were collected from a single
      brown trout S. trutta. All nonspecific gyrodactylid infections on salmonids were
      judged to be temporary, because only a few specimens were observed on each of the
      small number of infected fishes. The prevalence of endemic G. salaris was also
      low, only 1% (Nfish = 296) in Lake Onega and 0.7% (Nfish = 255) in Lake Ladoga,
      while brown trout specific Gyrodactylus species were not observed on any of the
      429 trout examined from the Ladoga basin. The host-specific and unspecific burden
      of Gyrodactylus spp. on these 'glacial relict' populations of salmon and brown
      trout was very low, suggesting a generalised resistance against the co-evolved
      freshwater parasite community, or some kind of 'vaccination' effect. These
      hypotheses deserve further testing.

PMID- 18038201
TI  - Myrmeconema neotropicum n. g., n. sp., a new tetradonematid nematode parasitising
      South American populations of Cephalotes atratus (Hymenoptera: Formicidae), with
      the discovery of an apparent parasite-induced host morph.
AB  - A new genus and species of tetradonematid nematode, Myrmeconema neotropicum n.
      g., n. sp., is described from larval, pupal and adult stages of Cephalotes
      atratus L. (Hymenoptera: Formicidae) in Peru and Panama. Diagnostic characters of
      the new genus include: males and females subequal in size; cuticle with minute
      annulations; six cephalic papillae; stylet present in all stages; stichocytes
      absent; trophosome degenerate; three penetration glands; gonads paired and
      opposite; vulva in mid-body region; single spicule; genital papillae absent;
      adult tails rounded; infective juveniles moult once in egg; and adults of both
      sexes remain in the host throughout their development. As the female nematodes
      mature inside the worker ants, the host gasters change colour from black to red.

PMID- 18038203
TI  - Synthesis and luminescent properties of lanthanide complexes with a novel
      multipodal ligand.
AB  - Solid complexes of lanthanide nitrates, picrates and perchlorates with a novel
      multipodal ligand, 1,2,4,5-tetramethyl-3,6-bis{N,N-bis[((2'
      benzylaminoformyl)phenoxyl)ethyl]-aminomethyl}-benzene (L) have been synthesized
      and characterized by elemental analysis, infrared spectra and molar conductivity
      measurements. At the same time, the luminescent properties of the Eu and Tb
      complexes in solid state were investigated. Under the excitation of UV light,
      these complexes exhibited characteristic emission of central metal ions. The
      lowest triplet state energy level T(1) of this ligand matches better to the
      lowest resonance energy level of Tb(III) than to Eu(III) ion. The influence of
      the counter anion on the luminescent intensity was also discussed.

PMID- 18038202
TI  - Multiple mechanisms account for lower plasma iron in young copper deficient rats.
AB  - Copper deficiency lowers brain copper and iron during development. The reduced
      iron content could be due to hypoferremia. Experiments were conducted to evaluate
      plasma iron and "ferroxidase" hypotheses by determining copper and iron status of
      Holtzman albino rats following gestational/lactational copper deficiency. Copper
      deficient (Cu-) dams on treatment for 5 weeks, two of gestation and three of
      lactation, had markedly lower copper content of milk and mammary tissue, and
      lower milk iron. Newborn pups from Cu- dams had lower copper and iron
      concentrations. Compared to Cu+ pups, Cu- pups, analyzed between postnatal age
      (P) 0 and P26, were smaller, anemic, had lower plasma iron, cardiac hypertrophy,
      and near zero ceruloplasmin activity. Liver copper in Cu+ pups increased then
      decreased during development and major reductions were evident in Cu- pups. Liver
      iron in Cu+ pups decreased with age while nursing but increased after eating
      solid food. Liver iron was lower in Cu- pups at P0 and P13 and normal at P20 and
      P26. Small intestinal copper decreased with age in Cu+ pups and was lower in Cu-
      pups. Intestinal iron levels in Cu- pups were higher than Cu+ pups postweaning in
      some experiments. Reduction in plasma iron in Cu- pups is likely due to a
      decreased "ferroxidase" function leading to lower placental iron transport, a
      lower milk iron diet, and partial block in iron uptake from intestine but is not
      due to failure to mobilize hepatic iron, in contrast to older rats eating diet
      with adequate iron.

PMID- 18038204
TI  - Absorption, fluorescence studies and ab initio calculations on binary mixture of
      p-dimethylaminobenzaldehyde.
AB  - Absorption as well as fluorescence emission studies of p
      dimethylaminobenzaldehyde (DMABA) in solvents with different polarity have been
      reported by varying the concentration of the solute. Dual fluorescence
      corresponding to the non-polar (NP) and twisted intramolecular charge transfer
      (TICT) states has been observed. The optimized geometry of DMABA was evaluated
      using ab-initio theory at various levels. The optimized geometries of the
      hydrogen bonded complexes with the solvent molecules were also calculated with
      the theory Hartree Fock at the basis set 6-31+G (HF/6-31+G). The results have
      been used to understand the structure of the molecule and the spectral changes in
      terms of hydrogen bonding and solute-solvent interaction.

PMID- 18038205
TI  - Effect of polymer strengtheners on the local environment of biocompatible glass
      as probed by fluorescence.
AB  - Mixed silica-calcite matrices were prepared by developing a "low" temperature
      (sol-gel) method in presence of several biocompatible polymers, thus providing
      samples with adequate porosity for the flow of biological fluids and also
      mechanically robust. In order to analyse and characterise the sample's
      microenvironments, the highly solvatochromic probe Nile red was used, which
      enabled the role of polymer addition upon local environmental effects in the host
      media to be elucidated. The polymers used were polyethylene glycol,
      polymethylmethacrylate and polyethylene. Each matrix was also characterized with
      respect to microstructure, morphology and pore size via the use of X-ray
      diffractometry and scanning electron microscopy. The results show that is was
      possible to obtain, in a controlled way, mixed silica-calcite matrices with a
      wide range of porosities (important if the material is to be used for scaffold or
      drug release applications, for example). The spectroscopic behaviour of Nile red
      when incorporated has confirmed the existence of distinct and specific local
      polarities within each type of matrix that may determine to a large extent the
      mechanism of interaction between these matrices and biological molecules.

PMID- 18038206
TI  - CancerLectinDB: a database of lectins relevant to cancer.
AB  - The role of lectins in mediating cancer metastasis, apoptosis as well as various
      other signaling events has been well established in the past few years. Data on
      various aspects of the role of lectins in cancer is being accumulated at a rapid
      pace. The data on lectins available in the literature is so diverse, that it
      becomes difficult and time-consuming, if not impossible to comprehend the
      advances in various areas and obtain the maximum benefit. Not only do the lectins
      vary significantly in their individual functional roles, but they are also
      diverse in their sequences, structures, binding site architectures, quaternary
      structures, carbohydrate affinities and specificities as well as their potential
      applications. An organization of these seemingly independent data into a common
      framework is essential in order to achieve effective use of all the data towards
      understanding the roles of different lectins in different aspects of cancer and
      any resulting applications. An integrated knowledge base (CancerLectinDB)
      together with appropriate analytical tools has therefore been developed for
      lectins relevant for any aspect of cancer, by collating and integrating diverse
      data. This database is unique in terms of providing sequence, structural, and
      functional annotations for lectins from all known sources in cancer and is
      expected to be a useful addition to the number of glycan related resources now
      available to the community. The database has been implemented using MySQL on a
      Linux platform and web-enabled using Perl-CGI and Java tools. Data for individual
      lectins pertain to taxonomic, biochemical, domain architecture, molecular
      sequence and structural details as well as carbohydrate specificities. Extensive
      links have also been provided for relevant bioinformatics resources and
      analytical tools. Availability of diverse data integrated into a common framework
      is expected to be of high value for various studies on lectin cancer biology.
      CancerLectinDB can be accessed through
      http://proline.physics.iisc.ernet.in/cancerdb .

PMID- 18038207
TI  - Presence and characterization of the dopamine transporter in human resting
      lymphocytes.
AB  - The paucity of information on the presence of the dopamine transporter (DAT) in
      blood cells, prompted us to explore it in human resting lymphocytes by means of
      the binding of 3H-WIN 35,428, a compound which is currently considered the most
      selective ligand for labelling this protein, and by means of the specific
      reuptake of 3H-dopamine (3H-DA). Lymphocytes were obtained by 15 healthy
      subjects. The results showed the presence of a specific and saturable binding of
      3H-WIN 35,428, which labelled one site only. A specific 3H-DA reuptake was also
      measured. The pharmacological characterization of both binding and reuptake was
      overlapping. These findings would indicate that human resting lymphocytes carry
      the DAT, whose functions in periphery are still unknown.

PMID- 18038208
TI  - A modified percutaneous transhepatic variceal embolization with 2-octyl
      cyanoacrylate versus endoscopic ligation in esophageal variceal bleeding
      management: randomized controlled trial.
AB  - BACKGROUND: Conventional percutaneous transhepatic varices embolization (PTVE)
      has rarely been used in recent years due to high rates of variceal recurrence and
      rebleeding. Herein we report a modified PTVE with 2-octyl cyanoacrylate (2-OCA)
      in which the whole lower esophageal and peri or para-esophageal varices, the
      submucosal varices, and the advertitial plexus of the cardia and fundus were
      sufficiently obliterated. We compared this PTVE with endoscopic band ligation
      (EVL) in the treatment of esophageal variceal bleeding. METHODS: In this
      prospective randomized controlled trial, cirrhotic patients with acute or recent
      esophageal variceal bleeding were assigned randomly to PTVE (52 patients) or EVL
      (50 patients) groups. Upper gastrointestinal (UGI) rebleeding, esophageal
      variceal rebleeding, and survival were followed-up. Computerized tomography (CT)
      scanning and portal venography were used to observe 2-OCA distribution. RESULTS:
      During the follow-up period (median 24 and 25 months in the PTVE and EVL groups,
      respectively) UGI rebleeding developed in eight patients in the PTVE group and 21
      patients in EVL group (P = 0.004). Recurrent bleeding from esophageal varices
      occurred in three patients in the PTVE group and twelve in the EVL group (P =
      0.012, relative risk 0.24, 95% confidence interval 0.05-0.74). Multivariate Cox
      analysis indicated that the treatment was the only factor predictive of
      rebleeding. A Kaplan-Meier curve showed there was no significant difference
      between survival in the two groups (P = 0.054). CONCLUSIONS: With the whole lower
      esophageal and peri or para-esophageal varices, the submucosal varices, and the
      adventitial plexus of the cardia and fundus sufficiently obliterated by 2-OCA,
      this modified PTVE was more effective than EVL in the management of esophageal
      varices recurrence and rebleeding. Survival in these two groups was not
      significantly different, however.

PMID- 18038210
TI  - Socioeconomic inequalities in unintended pregnancy and abortion decision.
AB  - Pregnancy planning allows women to better control their life trajectory and
      contributes to the future child's health and development. Many studies that have
      analyzed socioeconomic inequalities in unintended pregnancy only took into
      account those pregnancies ending in births. Few of them that analyzed unintended
      pregnancy, including both induced abortion and births, and its socioeconomic
      determinants, concluded that unintended pregnancy is more frequent in young,
      poor, or unmarried women. These inequalities have been poorly studied in Europe,
      especially in the southern European context. The aim of the present study is to
      describe socioeconomic inequalities in unintended pregnancy and in abortion
      decision in Barcelona, Spain. The major findings are that unintended pregnancies
      accounted for 41% of total pregnancy and of these, 60% ended in abortion. From
      all pregnancies, the proportion of induced abortion reached 25.6%. Compared to
      women with university studies, those with primary education incomplete had more
      unintended pregnancies (OR=7.22). When facing an unintended pregnancy, women of
      lower socioeconomic position are more likely to choose induced abortion, although
      this is not the case among young or single women. This study reveals deep
      socioeconomic inequalities in unintended pregnancies and abortion decision in
      Barcelona, Spain, where the birth rate is very low and the abortion rate is
      rising. Women in low socioeconomic positions have many more unintended
      pregnancies than better educated women. Except for young or single women, the
      lower the socioeconomic position, the higher the proportion of women who choose
      an induced abortion when facing an unintended pregnancy.

PMID- 18038211
TI  - Social network-related risk factors for bloodborne virus infections among
      injection drug users receiving syringes through secondary exchange.
AB  - Secondary syringe exchange (SSE) refers to the exchange of sterile syringes
      between injection drug users (IDUs). To date there has been limited examination
      of SSE in relation to the social networks of IDUs. This study aimed to identify
      characteristics of drug injecting networks associated with the receipt of
      syringes through SSE. Active IDUs were recruited from syringe exchange and
      methadone treatment programs in Montreal, Canada, between April 2004 and January
      2005. Information on each participant and on their drug-injecting networks was
      elicited using a structured, interviewer-administered questionnaire. Subjects'
      network characteristics were examined in relation to SSE using regression models
      with generalized estimating equations. Of 218 participants, 126 were SSE
      recipients with 186 IDUs in their injecting networks. The 92 non-recipients
      reported 188 network IDUs. Networks of SSE recipients and non-recipients were
      similar with regard to network size and demographics of network members. In
      multivariate analyses adjusted for age and gender, SSE recipients were more
      likely than non-recipients to self-report being HIV-positive (OR=3.56 [1.54
      8.23]); require or provide help with injecting (OR=3.74 [2.01-6.95]); have a
      social network member who is a sexual partner (OR=1.90 [1.11-3.24]), who
      currently attends a syringe exchange or methadone program (OR=2.33 [1.16-4.70]),
      injects daily (OR=1.77 [1.11-2.84]), and shares syringes with the subject
      (OR=2.24 [1.13-4.46]). SSE is associated with several injection-related risk
      factors that could be used to help focus public health interventions for risk
      reduction. Since SSE offers an opportunity for the dissemination of important
      prevention messages, SSE-based networks should be used to improve public health
      interventions. This approach can optimize the benefits of SSE while minimizing
      the potential risks associated with the practice of secondary exchange.

PMID- 18038212
TI  - Painful bladder syndrome/interstitial cystitis and vulvodynia: a clinical
      correlation.
AB  - Vulvodynia affects 25% of women with painful bladder syndrome/interstitial
      cystitis (PBS/IC). The objective of our study was to clinically evaluate the
      association of PBS/IC and vulvodynia and possible contributing factors. To our
      knowledge, this has not been reported. Seventy women with PBS/IC were evaluated
      from December 2005 to December 2006 with a comprehensive history and exam. Two
      groups were formed--those with vulvodynia and those without vulvodynia for
      comparison. Of the women, 51.4% had vulvodynia and 48.6% did not have vulvodynia
      using our operative definition. Average levator pain levels were significantly
      greater in those with vulvodynia. There was no significant difference in the
      total number of lifetime pelvic surgeries, history of sexually transmitted
      infections (STIs), vaginitis, or abuse history between groups. The correlation of
      vulvodynia and PBS/IC may have been underestimated. Research needs to explore the
      link between precipitating factors, symptoms, and effective treatment options for
      PBS/IC and vulvodynia.

PMID- 18038213
TI  - Seasonal fluctuations of bacterial community diversity in agricultural soil and
      experimental validation by laboratory disturbance experiments.
AB  - Natural fluctuations in soil microbial communities are poorly documented because
      of the inherent difficulty to perform a simultaneous analysis of the relative
      abundances of multiple populations over a long time period. Yet, it is important
      to understand the magnitudes of community composition variability as a function
      of natural influences (e.g., temperature, plant growth, or rainfall) because this
      forms the reference or baseline against which external disturbances (e.g.,
      anthropogenic emissions) can be judged. Second, definition of baseline
      fluctuations in complex microbial communities may help to understand at which
      point the systems become unbalanced and cannot return to their original
      composition. In this paper, we examined the seasonal fluctuations in the
      bacterial community of an agricultural soil used for regular plant crop
      production by using terminal restriction fragment length polymorphism profiling
      (T-RFLP) of the amplified 16S ribosomal ribonucleic acid (rRNA) gene diversity.
      Cluster and statistical analysis of T-RFLP data showed that soil bacterial
      communities fluctuated very little during the seasons (similarity indices between
      0.835 and 0.997) with insignificant variations in 16S rRNA gene richness and
      diversity indices. Despite overall insignificant fluctuations, between 8 and 30%
      of all terminal restriction fragments changed their relative intensity in a
      significant manner among consecutive time samples. To determine the magnitude of
      community variations induced by external factors, soil samples were subjected to
      either inoculation with a pure bacterial culture, addition of the herbicide
      mecoprop, or addition of nutrients. All treatments resulted in statistically
      measurable changes of T-RFLP profiles of the communities. Addition of nutrients
      or bacteria plus mecoprop resulted in bacteria composition, which did not return
      to the original profile within 14 days. We propose that at less than 70%
      similarity in T-RFLP, the bacterial communities risk to drift apart to inherently
      different states.

PMID- 18038215
TI  - Aspirin: recent developments.
AB  - Aspirin exerts anti-thrombotic action by acetylating and inactivating
      cyclooxygenase-1, preventing the production of thromboxane A2 in platelets.
      Through this inhibition of platelet function, aspirin is considered as a
      preventative of ischemic diseases such as coronary and cerebral infarction.
      However, many studies have revealed that aspirin has other beneficial actions in
      addition to its anti-platelet activity. For example, aspirin may confer some
      benefit against colorectal cancer. Here, we discuss the involvement of
      inflammation in atherosclerosis and how aspirin exerts its beneficial actions in
      atherosclerotic diseases and cancer.

PMID- 18038216
TI  - Neuroactive steroids: state of the art and new perspectives.
AB  - Neuroactive steroids include synthetic steroidal compounds and endogenous
      steroids, produced by endocrine glands (hormonal steroids) or the nervous tissue
      (neurosteroids), which regulate neural functions. These steroids bind to nuclear
      receptors or act through the activation of membrane-associated signaling pathways
      to modulate various important processes including the development of the nervous
      system, neural plasticity and the adaptive responses of neurons and glial cells
      under pathological conditions. Reviewed and updated in the present paper are the
      pleiotropic and protective abilities of neuroactive steroids. The fundamental
      evidence and knowledge gained constitute a profound background that offers
      interesting possibilities for developing effective strategies against several
      disorders of the nervous system.

PMID- 18038217
TI  - Endoplasmic reticulum stress responses.
AB  - In homeostasis, cellular processes are in a dynamic equilibrium. Perturbation of
      homeostasis causes stress. In this review I summarize how perturbation of three
      major functions of the endoplasmic reticulum (ER) in eukaryotic cells -- protein
      folding, lipid and sterol biosynthesis, and storing intracellular Ca(2+) --
      causes ER stress and activates signaling pathways collectively termed the
      unfolded protein response (UPR). I discuss how the UPR reestablishes homeostasis,
      and summarize our current understanding of how the transition from protective to
      apoptotic UPR signaling is controlled, and how the UPR induces inflammatory
      signaling.

PMID- 18038219
TI  - Anaerobic fermentative production of lactic acid using cheese whey and corn steep
      liquor.
AB  - Cheese whey was the most suitable substrate for production of lactic acid under
      anaerobic conditions by Entercoccus flavescens which, on supplementating with
      corn steep liquor (5% v/v) and 10 mM CaCO(3) at pH 5.5, 37 degrees C, yielded
      12.6 g lactic acid/l in 36 h. Production was scaled up to a 10 l bioreactor under
      controlled pH and continuous CO(2) supply and gave 28 g lactic acid/l in 30 h
      resulting in a net 8.7-fold increase in production as compared to unoptimized
      conditions.

PMID- 18038218
TI  - Phase II study of ispinesib in recurrent or metastatic squamous cell carcinoma of
      the head and neck.
AB  - Ispinesib (SB-715992) inhibits the mitotic kinesin spindle protein (KSP), a novel
      target for anticancer therapy. A phase II study was conducted to examine the
      efficacy of ispinesib in recurrent or metastatic head and neck squamous cell
      carcinoma (RMHNSC). Patients with up to one prior line of chemotherapy for RMHNSC
      were treated with ispinesib 18 mg/m2 IV over 1 hour every 21 days. Twenty-one
      patients were enrolled onto this study with a target stage I sample size of 19.
      Of 20 evaluable patients, no objective responses were seen and stable disease > 2
      cycles was observed in five patients (25%). The median time to progression was
      1.4 (95% CI 1.3-2.3) months, median survival was 3.5 (95% CI 2.8-7.8) months, and
      1 year overall survival was 20% (95% CI 8.3-48.1%). The most frequent
      attributable grades III-V adverse events were neutropenia (60% of patients) and
      leukopenia (55%). The pharmacokinetic profile was consistent with results from
      phase I studies. Archival tissues (n = 14) demonstrated low to moderate KSP
      expression by immunohistochemistry. In addition, no pharmacodynamic changes were
      observed in peripheral blood mononuclear cells. We detected no antitumor activity
      of ispinesib in RMHNSC on this dosing schedule.

PMID- 18038220
TI  - Occurrence of multiple sexual chromosomes (XX/XY1Y2 and Z1Z1Z2Z2/Z1Z2W1W2) in
      catfishes of the genus Ancistrus (Siluriformes: Loricariidae) from the Amazon
      basin.
AB  - Loricariid catfishes show a predominance of homomorphism in sex chromosomes, but
      cases of simple and multiple systems were also found. Here we describe two cases
      of multiple sex chromosome systems in loricariids from Brazilian Amazonia. Males
      of Ancistrus sp.1 "Balbina" have a modal number of 2n = 39 chromosomes,
      fundamental number (FN) of 78, and karyotypic formula of 27 m + 10 sm + 2 st;
      females have 2n = 38 chromosomes, FN = 76, and 26 m + 10 sm + 2 st. Ancistrus
      sp.2 "Barcelos" has 2n = 52 chromosomes for both sexes, FN = 80 for males and FN
      = 79 for females. Karyotypic formula is 12 m + 12 sm + 4 st + 24a for males and
      11 m + 12 sm + 4st + 25a for females. The two species show different arrangements
      of constitutive heterochromatin blocks, which are coincident with NORs and absent
      in sex chromosomes. We suggest a XX/XY(1)Y(2) mechanism for Ancistrus sp.1
      "Balbina", and a Z(1)Z(1)Z(2)Z(2)/Z(1)Z(2)W(1)W(2) mechanism for Ancistrus sp.2
      "Barcelos". The XX/XY(1)Y(2) mechanism here reported is the second known
      occurrence of this type of multiple sex chromosomes for Loricariidae and the
      third for Neotropical fishes; the mechanism Z(1)Z(1)Z(2)Z(2)/Z(1)Z(2)W(1)W(2)
      represents the first record among fishes. The presence of different sex
      chromosome systems in Ancistrus indicates a probable independent origin and
      suggests that the differentiation of sex chromosomes is evolutionarily recent
      among species in this genus.

PMID- 18038221
TI  - [Conventional navigation without computer and the lateral minimally invasive
      approach for contract valgus knee].
AB  - Valgus arthritic knees can basically be operated on by either a standard medial
      or a specific lateral approach. The classic lateral approach according to Keblish
      has some advantages, but also some disadvantages, relative to the standard medial
      parapatellar approach. A less invasive lateral approach means that osteotomy of
      tibia tubercle and eversion of the patella is no longer necessary. In view of our
      positive experiences with the minimally invasive surgical technique used for
      implantation of the lateral unicondylar prosthesis and for total knee
      arthroplasty in the case of varus knees, we have developed a minimally invasive
      lateral technique for use in valgus knees. The approach is a modification of the
      classic lateral approach used by Keblish. The procedure involves a lateral mini
      arthrotomy with no need for osteotomy of the tubercle or eversion of the patella,
      and the surgery takes place step by step from a lateral approach. Modified
      cutting standard instruments are used. All operations have been carried out using
      "conventional navigation" without computers. This consists in preoperative
      planning based on radiographs of the whole leg, intraoperative controls before
      and after bone cuts, planning of the rotational positioning of the femur and
      tibia and postoperative checks of the alignment on standing radiographs of the
      whole leg. Preliminary results observed in the first 63 consecutive patients
      (average age 45-85 years) with contract valgus deformity [average 12 degrees
      valgus (6-19 degrees )] are very promising. Since 2004 we have used minimally
      invasive medial and lateral mini-midvastus approaches routinely for nearly all
      our primary total knee arthroplasties.

PMID- 18038222
TI  - Effects of acute tyrosine/phenylalanine depletion on the selective processing of
      smoking-related cues and the relative value of cigarettes in smokers.
AB  - RATIONALE: Acute tyrosine/phenylalanine depletion (ATPD) is a validated
      neurobiological challenge that results in reduced dopaminergic neurotransmission,
      allowing examination of the effects of a hypodopaminergic state on craving
      related processes. OBJECTIVES: We studied 16 nonabstaining smokers (>10
      cigarettes/day; 9 males; age 20-33 years) to whom was administered a
      tyrosine/phenylalanine-free mixture (TYR/PHE-free) and a balanced amino acid
      mixture (BAL) in a double-blind, counterbalanced, crossover design. METHODS:
      Subjective cigarette craving, attentional bias to smoking-related word cues,
      relative value of cigarettes, negative mood, and expired carbon monoxide (CO)
      levels were measured at various timepoints through 300 min. Participants smoked
      at hourly intervals to prevent acute nicotine withdrawal during testing. RESULTS:
      The TYR/PHE-free mixture, as compared to the BAL mixture, was associated with a
      greater increase in CO levels from baseline (p = 0.01). Adjusting for the
      potential confounding influence of between-condition differences in CO levels
      across time, TYR/PHE-free mixture was associated with increased demand for
      cigarettes (p = 0.01) and decreased attentional bias toward smoking-related words
      (p = 0.003). There were no significant differences between conditions in either
      subjective craving or depressed or anxious mood (p values > 0.05). CONCLUSION:
      Among nonabstaining daily smokers, acute dopaminergic depletion via ATPD may
      influence smoking behavior and indices of smoking-related motivation, such as
      attentional bias to smoking cues and relative cigarette value, which are not
      readily captured by subjective craving.

PMID- 18038225
TI  - Differentiation of certified brands of origins of Spanish white wines by HS-SPME
      GC and chemometrics.
AB  - A headspace solid-phase microextraction gas-chromatographic (HS-SPME-GC)
      procedure was used to determine the composition of the volatile fraction of white
      wine samples from several Spanish certified brands of origin (CBO). The compounds
      present were previously identified by gas chromatography-mass spectrometry (GC
      MS) and quantitative determinations were carried out by GC-FID. Four CBO, Rueda,
      Ribeiro, Penedes, and Condado de Huelva, were studied. Rueda wines present the
      highest concentrations of ethyl acetate (55.86-125.27 microg mL(-1)), isoamyl
      acetate (0.91-6.72 microg mL(-1)), hexyl acetate (0.09-0.81 microg g mL(-1)), and
      2-phenethyl acetate (0.14-0.66 microg mL(-1)). Compounds such as ethyl hexanoate
      (0.88-2.15 microg mL(-1)) and ethyl decanoate (0.29-0.96 microg mL(-1)) appeared
      in higher concentration in Ribeiro, Rueda, and Penedes samples. According to the
      results obtained and by applying pattern-recognition procedures differentiation
      of the considered CBO was attained. Principal-component analysis (PCA), linear
      discriminant analysis (LDA), and multilayer perceptrons neural networks (MLP-NN)
      were used as chemometric tools for pattern-recognition studies.

PMID- 18038223
TI  - Effects of smoking abstinence on adult smokers with and without attention deficit
      hyperactivity disorder: results of a preliminary study.
AB  - RATIONALE: Individuals with attention deficit hyperactivity disorder (ADHD) smoke
      at higher rates than the general population; however, little is known about the
      mechanisms underlying this comorbidity. OBJECTIVE: This study evaluated the
      effects of overnight abstinence on withdrawal symptoms and cognitive performance
      in adult smokers with and without ADHD. MATERIALS AND METHODS: Individuals
      smoking > or = 15 cigarettes per day were recruited from the community and
      underwent an evaluation to establish a diagnosis of ADHD (n = 12) or not (n =
      14). Withdrawal symptoms, mood, craving, cognitive performance, and smoking cue
      reactivity were measured during two laboratory sessions-in a 'Satiated' condition
      participants smoked up to and during the session while in an 'Abstinent'
      condition, participants were required to be smoking abstinent overnight and
      remain abstinent during the session. RESULTS: The effects of abstinence on ADHD
      and non-ADHD smokers did not differ for withdrawal symptom severity, mood,
      craving or cue reactivity. Significant Group x Condition interactions were
      observed for measures of attention and response inhibition on the Conners' CPT.
      For reaction time (RT) variability and errors of commission, the ADHD group
      exhibited greater decrements in performance after overnight abstinence compared
      to the non-ADHD group. The effects of abstinence on other cognitive measures
      (e.g., rapid visual information processing task, cued Go/No-Go task) did not
      differ between the two groups. CONCLUSION: This preliminary study is the first to
      systematically evaluate the effects of acute smoking abstinence in adult smokers
      diagnosed with ADHD. Individuals with the disorder may smoke at higher rates due
      to greater worsening of attention and response inhibition after abstinence.

PMID- 18038224
TI  - Modulation of human motor cortex excitability by quetiapine.
AB  - RATIONALE: Quetiapine is increasingly used for the treatment of patients with
      psychosis and bipolar disorder. However, the neurobiological mechanisms, which
      may account for the favourable risk/benefit profile of this drug, are not
      entirely understood. OBJECTIVES: Transcranial magnetic stimulation was used to
      investigate the effects of acute and repeated administration of quetiapine on
      cortical excitability in healthy volunteers. MATERIALS AND METHODS: Within a
      double-blind, placebo-controlled, randomized cross-over design motor threshold,
      intracortical inhibition, intracortical facilitation and cortical silent period
      were studied in 15 healthy volunteers before and after a single dose of placebo
      and 100 mg quetiapine. Additional measurements were performed after 5 days of
      daily intake of 100 mg quetiapine. RESULTS: We observed a significant
      prolongation of the cortical silent period after a single dose of quetiapine,
      whereas the placebo had no effects. After repeated administration, there was a
      trend towards CSP prolongation, which did not reach significance. However, plasma
      concentrations at this time point were relatively low, as measurements were
      performed 15 h after the last drug intake. Other parameters of cortical
      excitability remained unaffected. CONCLUSIONS: By lengthening CSP without
      affecting MT, ICI and ICF, quetiapine demonstrates a unique neurophysiological
      profile which differs distinctively from brain excitability profiles of typical
      antipsychotics such as haloperidol. Provided that the CSP prolongation reflects
      the antipsychotic potential of quetiapine, TMS may be developed as a tool to
      monitor neurobiological effects of quetiapine treatment in schizophrenic patients
      and to explore the efficacy of other antipsychotic drugs with a similar mode of
      action.

PMID- 18038226
TI  - Estimation of bacterial biomass in subsurface sediments by quantifying intact
      membrane phospholipids.
AB  - In an earlier study of deep subsurface sediments from Nankai Trough (ODP Leg 190,
      offshore Japan) we employed intact phospholipids (PLs) as molecular indicators of
      living microorganisms. The current study extends this work by quantifying
      absolute amounts of sedimentary PLs by liquid chromatography-mass spectrometry
      (LC-MS) and by converting PL data into cell numbers in order to improve methods
      to estimate the extent of bacterial life in the subsurface. Investigations were
      carried out on 90 cm short cores of Lake Baikal sediment. High amounts of
      identified intact PLs are interpreted as reflecting the constituents of living
      bacteria due to high organic matter decomposition and oxic mineralisation between
      the epilimnion and the sediment-water interface. Concentrations of ester-bound
      PLs reach up to 13,120 ng/g sediment dry weight. Predominance of ethanolamine and
      glycerol PL head groups confirms the bacterial origin. The most abundant side
      chain pairs are combinations including 14:0 and 16:0 fatty acids and to a minor
      extent 15:0 and 16:1 fatty acids. Depth profiles of PL concentrations converted
      from conventional PL fatty acid analysis are of the same order of magnitude and
      show comparable trends as those for intact PLs. An approximate estimation of
      bacterial cell numbers is inferred from intact PL quantification using LC-MS.

PMID- 18038227
TI  - Infrared spectroscopic study of microwave-sintered Pb(Zr,Ti)O3-based ceramics.
AB  - Infrared spectroscopy is often used to monitor the formation of the perovskite
      phase during the preparation of lead zirconate titanate (PZT) thin films and
      fibres and also to detect phase transitions. Infrared spectroscopy has rarely
      been used to investigate bulk samples or thick films of PZT. In this study, the
      first results of infrared investigations of microwave-sintered PZT and PZT
      reinforced with powdered copper are presented and compared with results from
      thermally heated samples. The infrared spectra show the typical Zr/TiO(6) metal
      oxygen octahedral vibrational modes in the range 750 to 450 cm(-1). This band is
      broadened for the pure PZT samples at higher sintering temperatures. A shift of
      the peak to lower wave numbers with increasing temperatures can be proven for
      pure PZT samples, but not for the Cu-reinforced PZT samples.

PMID- 18038229
TI  - Secondary structure and distribution of fusogenic LV-peptides in lipid membranes.
AB  - LV-peptides were designed as membrane-spanning low-complexity model structures
      that mimic fusion protein transmembrane domains. These peptides harbor a
      hydrophobic core sequence that consists of helix-promoting and helix
      destabilizing residues at different ratios. Previously, the fusogenicity of these
      peptides has been shown to increase with the conformational flexibility of their
      hydrophobic cores as determined in isotropic solution. Here, we examined the
      secondary structure, orientation, and distribution of LV-peptides in membranes.
      Our results reveal that the peptides are homogeneously distributed within the
      membranes of giant unilamellar liposomes and capable of fusing them. Increasing
      the valine content of the core up to the level of the beta-branched residue
      content of SNARE TMDs (approximately 50%) enhances fusogenicity while maintaining
      a largely alpha-helical structure in liposomal membranes. A further increase in
      valine content or introduction of a glycine/proline pair favors beta-sheet
      formation. In planar bilayers, the alpha-helices adopt oblique angles relative to
      the bilayer normal and the ratio of alpha-helix to beta-sheet responds more
      sensitively to valine content. We propose that the fusogenic conformation of LV
      peptides is likely to correspond to a membrane-spanning alpha-helix. Beta-sheet
      formation in membranes may be considered a side-reaction whose extent reflects
      conformational flexibility of the core.

PMID- 18038228
TI  - Rule-based standardised switching of drugs at the interface between primary and
      tertiary care.
AB  - INTRODUCTION: Changes in drug treatment are frequently mandatory with hospital
      admission and discharge because hospital drug formularies are generally
      restricted to about 3000 drugs as compared to the many times this number - 62,000
      in Germany - that are commercially available. Without computerised support, the
      process involved with switching drugs to a corresponding generic or a therapeutic
      equivalent is time-consuming and error-prone. METHODS: We have developed and
      tested a standardised interchange algorithm for subsequent implementation into a
      computerised decision support system that switches drugs to the corresponding
      generic or a therapeutic equivalent if they are not listed on the hospital drug
      formulary. RESULTS: The algorithm was retrospectively applied to the medication
      regimens of 120 patients (774 prescribed drugs containing 886 active ingredients)
      at their time of admission to surgical wards. Of the prescribed drugs, 52.8%
      (409/774) were part of the hospital drug formulary, thereby rendering a switch
      unnecessary. The 365 drugs not listed consisted of 392 active ingredients that
      were successfully switched to a corresponding generic (84.7%) or a therapeutic
      equivalent (10.2%). No specific switching procedures were defined for only 2.3%
      (20/886) of the active ingredients. In these cases, the drugs were either
      discontinued (4/20) or special drug classes, current diseases or co-medication
      required manual switching (8/20), or the drugs were continued unchanged and
      ordered from a wholesaler (8/20). CONCLUSION: Using a standardised interchange
      algorithm, pre-admission drug regimens can successfully be switched to drugs on a
      hospital drug formulary. These findings suggest that a computerised decision
      support system will likely be useful to support this important practice.

PMID- 18038230
TI  - Percutaneous radiofrequency ablation: relationship between different probe types
      and procedure time on length and extent of osteonecrosis in dog long bones.
AB  - PURPOSE: We have been using radiofrequency ablation for the percutaneous
      treatment of osteoid osteoma since 2001. Frequently, lesions are located near the
      joint surface, involve the vertebral body or are close to major nerves. We seek
      to determine whether radiofrequency ablation (RFA) can be used safely in these
      cases. MATERIALS AND METHODS: A total of 65 lesions were induced in 4 dogs. Each
      dog underwent RFA on the diaphysis of long bones, as well as femoral and humeral
      heads. Four different sessions were carried out by using 1- and 2-cm probes with
      or without a cool-tip system and by varying the timing of the procedure. Plain
      film, CT, and MRI were obtained. All bone samples were examined histologically.
      RESULTS: The dogs' activity after the procedure was normal. No pathologic
      fractures occurred despite unrestricted activity of the animals. Cortical bone
      was always respected; therefore, articular cartilage has not been damaged.
      Radiological findings were characteristic. There were no significant differences
      in lesion size, probe type, and the duration of the procedure. The mean lesion
      diameter perpendicular to the electrode was 18.5 mm. CONCLUSIONS: Our study
      confirms the insulative effect of cortical bone. RFA can be safely performed
      close to the joint surface without damaging the cartilage.

PMID- 18038231
TI  - Fixation with autogenous osteochondral grafts for the treatment of
      osteochondritis dissecans (stages III and IV).
AB  - This paper presents a clinical and functional assessment of the cases of
      osteochondritis dissecans (OCD) treated with small mosaicplasty type
      osteochondral grafts. Between 1999 and 2004, we operated on 12 knees with OCD
      stages III and IV. They were assessed using the International Cartilage Research
      Society (ICRS) scale, the Visual Analogue Scale (VAS) scale, X-ray and magnetic
      resonance imaging (MRI). The study was carried out using a clinical series, was
      retrospective and had a level of evidence of 4. Before surgery, all patients were
      in classes III and IV on the ICRS scale (four in class III and eight in class
      IV). At the time of surgery, the patient age was 27.5 +/- 7.9 years, with male
      predominance (75%). Eleven of the cases were assessed as classes I and II on the
      ICRS scale (seven in class I and four in class II), with one patient in class IV.
      X-ray assessment was less favourable, revealing alterations in the articular
      space in 75% of cases. The results show that this technique enables the
      biological fixation of fragments and, functionally, the clinical results obtained
      were very good. The osteochondral grafts avoid the implantation of foreign
      material and make use of bone fragments of the same rigidity as the OCD fragment.
      We conclude that the technique described is an excellent alternative to the
      techniques normally used for the fixation of stage III and IV OCD.

PMID- 18038233
TI  - Initial experience on efficacy in closure of cryptoglandular and Crohn's
      transsphincteric fistulas by the use of the anal fistula plug.
AB  - BACKGROUND AND AIMS: It was the aim of this prospective study to analyze the
      efficacy of the Cook Surgisis AFP anal fistula plug (AFP) for the closure of
      cryptoglandular and Crohn's disease-associated transsphincteric anorectal
      fistulas. MATERIALS AND METHODS: All patients with transsphincteric anorectal
      fistulas who underwent a surgical procedure using the AFP were prospectively
      enrolled in this study. Inclusion criteria included transsphincteric, single
      tract fistulas. Patients' demographics, fistula etiology, surgical variables,
      continence (Cleveland Clinic Florida incontinence score), quality of life (fecal
      incontinence quality of life), and success rates were prospectively recorded.
      Surgery was performed in a standardized technique including irrigation of the
      fistula tract, placement, and internal fixation of the Cook Surgisis AFP anal
      fistula plug. No flap or excision of the fistula tract was performed. Success was
      defined as closure of both internal and external openings, absence of drainage
      without further intervention, and absence of abscess formation. Follow-up
      information was derived from clinical examination 3, 6, 9, and 12 months
      postoperatively. RESULTS: Within 6 months (August 2006 to January 2007), a total
      of 19 AFPs were inserted in 19 patients (8 females, 11 males; mean age, 38
      years). Out of 19 patients, 12 had cryptoglandular and 7 had Crohn's associated
      transsphincteric fistulas. Three patients were smokers, one patient had
      methicillin-resistant Staphylococcus aureus infection. Mean operative time was 15
      min (range, 8-22); no morbidity occurred. After a mean follow-up of 279 days (SD
      = 68.0) and one patient lost to follow-up, the overall success rate was 61% (12
      of 18) at 9 months postoperatively. Focusing solely on cryptoglandular fistulas,
      the success rate was 45.5% (5 of 11), whereas it was 85.7% (6 of 7) in
      transsphincteric fistulas associated with Crohn's disease. Five patients with
      failure of AFP (plug dislodgement, n = 2; persistent secretion, n = 3) had
      reoperation (27.8%). The reasons for failure were infection requiring drainage (n
      = 2) and persistent drainage (n = 3). No deterioration of continence was
      documented. CONCLUSION: The success rate for the Cook Surgisis AFP anal fistula
      plug for the closure of complex anorectal fistulas both in cryptoglandular and
      Crohn's associated fistulas was 45.5 and 85.7%, respectively. Further analysis is
      needed to explain the definite role of this innovative technique in comparison to
      traditional surgical techniques.

PMID- 18038234
TI  - Laparoscopic transvesical repair of recurrent vesicovaginal fistula using with
      fleece-bound sealing system.
AB  - BACKGROUND: Vesicovaginal fistula (VVF) is an epithelium-lined communication
      between the urinary bladder and vagina. Most of VVFs are repaired by conventional
      open surgery. Laparoscopic repair of VVFs is rare and so far no report is
      available about laparoscopic repair of persistent VVF using fleece-bound sealing
      system as a tissue barrier in the literature. Here we describe the operative
      technique and briefly review the literature. CASE: We present the case of a 37
      year-old woman with recurring VVF in two times after abdominal and transvaginal
      repairs caused by a massive bleeding during caesarian-section due to placenta
      previa and underwent hysterectomy. During the laparoscopic repair of the fistula
      and excision of the vaginal cuff, fleece-bound sealing system (TachoSil) was used
      as tissue barrier. Laparoscopic transperitoneal transvesical repair was
      successfully performed by suturing the defects and fixing two TachoSil between
      the bladder and vagina. The postoperative period of the patient was uneventful
      and after a follow up of 6 months no recurrence was found. CONCLUSION: We believe
      that laparoscopic repair of vesicovaginal fistula is a feasible and efficacious
      minimally invasive approach for the management of this entity. Whilst proper
      identification of tissue planes and good laparoscopic suturing technique are
      required, using fleece-bound sealing system might be convenient especially for
      persistent VVF.

PMID- 18038235
TI  - Unsuspected breast carcinoma presenting as orbital complication of
      rhinosinusitis.
AB  - We report a rare clinical presentation of breast carcinoma metastasis to the
      ethmoid sinuses, orbit and cavernous sinus in a 70-year-old lady with unsuspected
      breast carcinoma who presented with clinical features of acute ethmoiditis,
      orbital cellulitis and cavernous sinus thrombosis. The patient underwent
      endoscopic ethmoidectomy and histology of the necrotic tissue from the ethmoidal
      cells was positive for endovascular neoplastic emboli. Subsequent examination
      revealed a large mass in the left breast, tethered to the skin, which was
      histologically confirmed to be a carcinoma. The patient died 2 months post
      diagnosis. To our knowledge, this is the third case manifesting with combined
      features of ethmoiditis, orbital cellulitis and cavernous sinus syndrome from an
      unsuspected breast carcinoma. This case highlights the importance of imaging and
      thorough physical examination when a dramatic clinical picture presents in the
      paranasal sinuses of an otherwise healthy individual. Such manifestation of
      breast carcinoma is difficult to diagnose, and therefore, a high index of
      suspicion should be maintained. Skull base metastases from breast carcinoma
      behave aggressively and if diagnosed early, treatment may prolong survival and
      improve quality of life.

PMID- 18038236
TI  - Human bocavirus in children with acute lymphoblastic leukemia.
AB  - A new human parvovirus, human bocavirus, has recently been identified in
      respiratory secretions, feces and serum. It is associated with lower and most
      likely also upper respiratory tract infections. Most commonly reported symptoms
      are cough, rhinorrhea, expiratory wheezing and fever, and the virus is
      preferentially detected in young children. We report three children with acute
      lymphoblastic leukemia who had acute febrile episodes with concomitant detection
      of human bocavirus in their respiratory secretions. One of them had five
      consecutive febrile episodes during 6 months, all associated with the presence of
      human bocavirus at varying viral loads, suggesting prolonged shedding or
      reactivation of the virus.

PMID- 18038237
TI  - Goblet cells: are they an unspecific barrier against Giardia intestinalis or a
      gate?
AB  - Giardiosis is one of the major intestinal parasitic diseases of human beings as
      well as wild and domesticated animals. Several protective mechanisms against
      infection have been described. However, specific information about relationship
      between giardiosis and the increased proliferation of goblet cells (GC) in
      patients infected with Giardia intestinalis (Syn. G. duodenalis, G. lamblia) is
      scarce. In this work, we compare and quantify the number of GC, and have inferred
      their metabolic state in the small intestine of dogs parasitized with Giardia
      intestinalis compared to dogs without parasites. Small intestine segments were
      processed using routine methods for histology and electron microscopy; areas and
      cells were screened with an Axiovision Ver. 4.0 system. Data were analyzed by
      ANOVA and comparison of averages. Parasitized dogs showed higher GC numbers than
      nonparasitized ones. Averages were: 20+/-0.81 GC/25 microm(2) with independent
      mucin granules and 11+/-1.53 GC/25 microm(2) that were expelling mucus, compared
      to 11+/-0.94 GC/25 microm(2) and 1+/-0.27 GC/25 microm(2), respectively, in
      nonparasitized dogs (Tukey, p<0.001). The increases in GC number seem to be an
      unspecific defensive mechanism against Giardia trophozoites. However, we found
      some evidence supporting that GC hyperplasia could be a prejudicial to epithelial
      barrier that gives rise to gates allowing for Giardia-tissue invasion.

PMID- 18038238
TI  - Demonstration of Balamuthia and Acanthamoeba mitochondrial DNA in sectioned
      archival brain and other tissues by the polymerase chain reaction.
AB  - Granulomatous amoebic encephalitis (GAE) is a usually fatal disease caused by the
      free-living amoebae Balamuthia mandrillaris and Acanthamoeba spp. The intent of
      this study was to determine if the polymerase chain reaction (PCR) could be used
      retrospectively to detect amoeba mitochondrial 16S rRNA gene DNA in confirmed
      archival tissue sections from GAE cases stored in our laboratories for 1 to 34
      years. The DNA was extracted from deparaffinized sections, and appropriate primer
      sets for each of the two amoebae were used for amoeba DNA detection. Indirect
      immunofluorescent (IIF) staining of tissue sections was used as the standard for
      identification of amoebae against which the PCR results were compared. Sixty
      slides from a total of 56 cases were processed by PCR for amoeba 16S DNA. In 28
      slides (47%), there was agreement between the IIF and PCR results. In 41 of the
      slides (52%), no amoeba DNA was detected after PCR. In one slide (1%), the PCR
      and IIF results did not agree. While PCR supported IIF findings in about half of
      the slides, there are significant limitations in amoeba DNA identifications in
      formalin-fixed brain tissues. Degradation of amoeba DNA caused by formalin
      fixation was probably a factor in limiting valid results.

PMID- 18038240
TI  - Stage 2 hypertension in a child with a rapidly enlarging kidney: question.
      Burkitt's lymphoma.

PMID- 18038239
TI  - Renal manifestations of Dent disease and Lowe syndrome.
AB  - To date, two responsible genes for the development of Dent disease have been
      identified: CLCN5 and OCRL1. In this study, genotype-phenotype correlations were
      studied in patients with Dent disease and those with Lowe syndrome. Among the 12
      boys with a phenotype typical of Dent disease, nine had a mutation in CLCN5 (Dent
      disease 1), two had a mutation in OCRL1 (Dent disease 2), and one had no
      mutations in either gene. All seven boys with a clinical diagnosis of Lowe
      syndrome had a mutation in OCRL1. Patients with Lowe syndrome showed more
      frequent hypophosphatemia/rickets and more prominent tubular proteinuria than
      patients with Dent disease 1, and patients with Dent disease 2 had higher degree
      of tubular proteinuria and hypercalciuria than patients with Dent disease 1.
      Additionally, one patient with Dent disease 2 showed a mild degree of
      developmental delay, elevated serum muscle enzyme levels, and cryptorchidism. In
      this study, the genetic heterogeneity in Dent disease and the phenotypic
      heterogeneity in Lowe syndrome were confirmed. In patients with Dent disease, the
      presence of the above-mentioned extrarenal manifestations indicates that it is
      more likely that the patient is affected by Dent disease 2 than by Dent disease
      1.

PMID- 18038241
TI  - Stage 2 hypertension in a child with a rapidly enlarging kidney: answer.
      Burkitt's lymphoma.

PMID- 18038242
TI  - Detection of human bocavirus in Asturias, Northern Spain.

PMID- 18038243
TI  - Bone structural effects of variation in the TNFRSF1B gene encoding the tumor
      necrosis factor receptor 2.
AB  - The 1p36 region of the human genome has been identified as containing a QTL for
      BMD in multiple studies. We analysed the TNFRSF1B gene from this region, which
      encodes the TNF receptor 2, in two large population-based cohorts. Our results
      suggest that variation in TNFRSF1B is associated with BMD. INTRODUCTION: The
      TNFRSF1B gene, encoding the TNF receptor 2, is a strong positional and functional
      candidate gene for impaired bone structure through the role that TNF has in bone
      cells. The aims of this study were to evaluate the role of variations in the
      TNFRSF1B gene on bone structure and osteoporotic fracture risk in postmenopausal
      women. METHODS: Six SNPs in TNFRSF1B were analysed in a cohort of 1,190
      postmenopausal Australian women, three of which were also genotyped in an
      independent cohort of 811 UK postmenopausal women. Differences in phenotypic
      means for genotype groups were examined using one-way ANOVA and ANCOVA. RESULTS:
      Significant associations were seen for IVS1+5580A>G with BMD and QUS parameters
      in the Australian population (P = 0.008 - 0.034) and with hip BMD parameters in
      the UK population (P = 0.005 - 0.029). Significant associations were also
      observed between IVS1+6528G>A and hip BMD parameters in the UK cohort (P = 0.0002
      - 0.003). We then combined the data from the two cohorts and observed significant
      associations between both IVS1+5580A>G and IVS1+6528G>A and hip BMD parameters (P
      = 0.002 - 0.033). CONCLUSIONS: Genetic variation in TNFRSF1B plays a role in the
      determination of bone structure in Caucasian postmenopausal women, possibly
      through effects on osteoblast and osteoclast differentiation.

PMID- 18038244
TI  - Skeletal deterioration induced by RANKL infusion: a model for high-turnover bone
      disease.
AB  - RANKL was administered continuously to rats for 28 days to investigate its
      potential as a disease model for the skeletal system. Bone turnover rates, bone
      material, structural and mechanical properties were evaluated. RANKL infusion
      caused overall skeletal complications comparable to those in high bone-turnover
      conditions, such as postmenopausal osteoporosis. INTRODUCTION: RANKL is an
      essential mediator for osteoclast development. No study has examined in detail
      the direct skeletal consequences of excess RANKL on bone turnover,
      mineralization, architecture, and vascular calcification. We, therefore,
      administrated soluble RANKL continuously into mature rats and created a bone-loss
      model. METHODS: Six-month-old Sprague-Dawley (SD) rats were assigned to three
      groups (n = 12) receiving continuous administration of saline (VEH) or human
      RANKL (35 microg/kg/day, LOW or 175 microg/kg/day, HI) for 28 days. Blood was
      collected routinely during the study. At sacrifice, hind limbs and aorta were
      removed and samples were analyzed. RESULTS: High dose RANKL markedly stimulated
      serum osteocalcin and TRAP-5b levels and reduced femur cortical bone volume (
      7.6%) and trabecular volume fraction (BV/TV) at the proximal tibia (-64% vs.
      VEH). Bone quality was significantly degraded in HI, as evidenced by decreased
      femoral percent mineralization, trabecular connectivity, and increased
      endocortical bone resorption perimeters. Both cortical and trabecular bone
      mechanical properties were reduced by high dose RANKL. No differences were
      observed in the mineral content of the abdominal aorta. CONCLUSIONS: Continuous
      RANKL infusion caused general detrimental effects on rat skeleton. These changes
      are comparable to those commonly observed in high-turnover bone diseases such as
      postmenopausal osteoporosis.

PMID- 18038245
TI  - Age trends in proximal femur geometry in men: variation by race and ethnicity.
AB  - Data on bone architecture in diverse male populations are limited. We examined
      proximal femur geometry in 1,190 black, Hispanic, and white men. Cross-sectional
      analyses indicate greatest bone strength among black men, and greater age-related
      differences in bone strength among Hispanic men than other subjects at the narrow
      neck and intertrochanter regions of the proximal femur. INTRODUCTION: Although
      race/ethnic differences in bone mass are well-documented, less is known about
      differences in bone architecture. We examined proximal femur geometry in a
      diverse, randomly-sampled population of 1,190 community-dwelling men (age 30-79
      y). METHODS: Dual X-ray absorptiometry scans were obtained for 355 black, 394
      Hispanic, and 441 white subjects. Measures were obtained for the narrow neck
      (NN), intertrochanter (IT) and shaft regions of the proximal femur via hip
      structural analysis. Analyses considered bone mineral density (BMD, g/cm2), outer
      diameter (cm), cross-sectional area (CSA, cm2), section modulus (Z, cm3), and
      buckling ratio (BR). Results were adjusted for height, weight and physical
      activity level. RESULTS: Black subjects exhibited greater age-specific BMD, CSA
      and Z, than their white counterparts. For instance, at age 50 y, NN BMD was
      approximately 11% higher among black men (p < 0.001). Hispanic men exhibited
      sharper age-related differences in NN and IT BMD than did others. IT BMD, for
      instance, decreased by 2.4% with 10 y age among Hispanic subjects, but had
      virtually no age trend in others (p < 0.001). CONCLUSIONS: These results imply
      greater bone strength among black American men than among their white
      counterparts, and may indicate elevated fracture risk among older Hispanic
      American subpopulations.

PMID- 18038247
TI  - Description of by-product inhibiton effects on biodesulfurization of
      dibenzothiophene in biphasic media.
AB  - As several authors have reported previously, the Biodesulfurization of
      hydrodesulfurization recalcitrants, such as dibenzothiophene, is not yet
      commercially viable because mass transfer limitations and feedback inhibition
      effects are produced during the conversion. This work has been focused to
      investigate the inhibition process in aqueous and oil-water systems with two
      different aerobic biocatalysts types, Rhodococcus erythropolis IGTS8 and
      Pseudomonas putida CECT 5279. The results obtained have proven that global DBT
      desulfurization process using CECT 5279 was not clearly deactivated due to final
      product accumulation, under the experimental conditions assayed. Consistently,
      the desulfurization pattern has been described with the Michaelis-Menten
      equation, determining the kinetic parameters. On other hand, the assays have
      shown that important mass transfer limitations produced the decrease of the
      yields obtained with this Gram(-) strain in biphasic media. With strain IGTS8 it
      was observed lower mass transfer problems, but contrary the reaction was severely
      affected by the final product accumulation, in both aqueous and biphasic systems.
      Therefore it has been proposed an enzymatic kinetic model with competitive
      inhibition to describe the BDS evolution pattern when this Gram(+) strain was
      used.

PMID- 18038246
TI  - The effect of physician and health plan market concentration on prices in
      commercial health insurance markets.
AB  - The objective of this paper is to describe the market structure of health plans
      (HPs) and physician organizations (POs) in California, a state with high levels
      of managed care penetration and selective contracting. First we calculate
      Herfindahl-Hirschman (HHI) concentration indices for HPs and POs in 42 California
      counties. We then estimate a multivariable regression model to examine the
      relationship between concentration measures and the prices paid by HPs to POs.
      Price data is from Medstat MarketScan databases. The findings show that any
      California counties exhibit what the Department of Justice would consider high
      HHI concentration measures, in excess of 1,800. More than three quarters of
      California counties exhibit HP concentration indices over 1,800, and 83% of
      counties have PO concentration levels in excess of 1,800. Half of the study
      counties exhibited PO concentration levels in excess of 3,600, compared to only
      24% for plans. Multivariate price models suggest that PO concentration is
      associated with higher physician prices (p < or = 0.05), whereas HP concentration
      does not appear to be significantly associated with higher outpatient commercial
      payer prices.

PMID- 18038248
TI  - Chronic obstructive pulmonary disease and mortality following hip fracture: a
      population-based cohort study.
AB  - INTRODUCTION: Mortality rates after hip fracture have not declined in 20 years.
      We assessed the impact of chronic obstructive pulmonary disease (COPD) on
      mortality after hip fracture, and compared mortality in this cohort to persons
      without hip fracture in a population-based prospective cohort study. METHODS:
      Using Danish health care registries, we identified persons >or=40 years old with
      first-time hospitalization for hip fracture between 1/1/1998 and 1/31/2003.
      Hospitalization for COPD was assessed from hospital discharge registries. Using
      Cox regression, we computed relative risks (RR) and 95% confidence intervals (CI)
      for mortality endpoints among persons with COPD compared to persons without COPD.
      Mortality following hip fracture was also compared to age and gender matched
      controls without hip fracture. RESULTS: We identified 11, 985 persons with first
      time hospitalization for hip fracture; 771 (6.4%) had a diagnosis of COPD.
      Average follow up was 22 months. Compared to persons without COPD, mortality
      following hip fracture in persons with COPD was RR=1.58 (95% CI 1.30-1.90) at 30
      days, RR=1.52 (95% CI 1.30-1.77) at 90-days, RR=1.58 (95% CI 1.40-1.78) at 1
      year, and RR=1.71 (95% CI 1.55-1.88) overall. The 1-year mortality in persons
      with hip fracture and COPD was approximately 3-5 times greater than in controls
      without hip fracture. CONCLUSIONS: In this cohort, persons with COPD have a 60
      70% higher risk of death following hip fracture than those without COPD. In
      addition, hip fracture and COPD increased 1-year mortality 3-5 times that of
      persons without hip fracture.

PMID- 18038249
TI  - The influence of plectin deficiency on stability of cytokeratin18 in
      hepatocellular carcinoma.
AB  - Intermediate filaments are important in building the cellular architecture.
      Previously we found cytokeratin18 was modulated in human hepatocellular
      carcinoma. Plectin is a cross-linking protein that organizes the cytoskeleton
      into a stable meshwork, which can maintain the uniform size and shape of
      hepatocytes. Because the cells of hepatocellular carcinoma were morphologically
      different from the hepatocytes, we speculated that expression of plectin and
      organization of intermediate filament might play roles in the pleomorphism of
      hepatocellular carcinoma cells. In this paper, we studied the plectin expression
      of hepatocellular carcinoma and liver tissues by immunohistochemistry and
      immunoblot. The results revealed that plectin was deficient and cytokeratin18 was
      modulated in hepatocellular carcinoma. Furthermore, we knockdown the plectin mRNA
      in Chang cells, the result revealed the plectin was deficient and the
      organization of cytokeratin18 was altered. Conclusively, this study offers a
      hypothesis that plectin deficient might play an important role in the
      tumorigenesis of hepatocellular carcinoma.

PMID- 18038250
TI  - On the rising trends of incidence and prognosis for breast cancer patients
      diagnosed 1975-2004: a long-term population-based study in southeastern
      Netherlands.
AB  - BACKGROUND: Much progress has been made in the early diagnosis and treatment of
      breast cancer. We have assessed the changing burden of this disease, by means of
      a comprehensive description of trends in incidence, survival, and mortality.
      METHODS: Data on breast cancer patients diagnosed between 1975 and 2004 (n =
      26,464) registered in the population-based Eindhoven Cancer Registry were
      investigated. RESULTS: Incidence for patients aged below 40 and 40-49 has
      increased by 2.1% and 2.4% annually, since 1995 (p = 0.08 and p = 0.001,
      respectively). Mortality decreased in all age groups, but most markedly among
      women aged 50-69 (-1.5% yearly since 1985, p = 0.14). The proportion of stage I
      tumors increased from 25% to 39%, that of advanced stages (III & IV) decreased
      from 30% (1975-1984) to 13% in 1995-2004, and the proportion of in situ tumors
      increased from 1.5% to 10%. Adjuvant systemic treatment was administered to 15%
      of patients in 1975-1984 vs. 49% in 1995-2004. Relative 10-year survival rates
      for women aged 50-69 (period analysis) increased from 53% to 75% between 1975 and
      2004. The best prognosis was observed for women aged 45-54. Women younger than 35
      had a particularly poor prognosis. CONCLUSION: The observed improvement in
      survival of breast cancer patients during the last three decades is impressive.
      The peak in breast cancer incidence is not yet in sight considering the recent
      trends in exposure to known risk factors and improved diagnosis. The combination
      of increasing incidence and improved survival rates implies that the number of
      prevalent cases will continue to increase considerably in the next 10 years.

PMID- 18038251
TI  - RGS5 expression is a quantitative measure of pericyte coverage of blood vessels.
AB  - Pericytes play a key role in the process of vascular maturation and stabilization
      however, the current methods for quantifying pericyte coverage of the
      neovasculature are laborious and subjective in nature. In this study, we have
      developed an objective, sensitive, and high-throughput method for quantifying
      pericyte coverage of angiogenic vessels by analyzing the expression of the
      pericyte-specific gene, the regulator of G-protein signaling 5 (RGS5). We
      determined that RGS5 expression was up-regulated during a defined developmental
      time period in which nascent vessel sprouts acquired a pericyte covering.
      Furthermore, RGS5 expression was dramatically reduced in vessels with poor
      pericyte coverage compared to normal angiogenic vasculature. Finally, we
      determined that the susceptibility of nascent vessels to regression by vascular
      endothelial growth factor (VEGF) inhibition was significantly reduced following
      RGS5 up-regulation, further implicating RGS5 in pericyte-endothelial cell
      interactions and the vascular maturation process. These studies establish the use
      of RGS5 gene expression as a quantitative and robust measure of pericyte coverage
      of neovasculature. This method provides a tool for vascular biologists studying
      pericyte-endothelial cell interactions and vascular maturation in both normal and
      pathological conditions, such as diabetic retinopathy and cancer.

PMID- 18038252
TI  - Characterisation of potential virulence markers in Pseudomonas aeruginosa
      isolated from drinking water.
AB  - Pseudomonas aeruginosa isolates from tap water, mineral water, and artesian well
      water were investigated for their ability to produce different potential
      virulence factors or markers such as hemolysins, hemaglutinins, cytotoxins and
      their ability to adhere to epithelial cells and to abiotic surfaces. The
      susceptibility to antibiotics, human serum sensitivity and the survival of P.
      aeruginosa isolates in a chlorinated environment were also examined. Of the 30
      isolates tested, 16 possessed the capacity to adhere to abiotic surfaces, and 28
      to adhere to epithelial cells; 30 were capable of producing hemolysins, 27
      produced cytotoxins, 9 hemagglutinins, and 18 were classified as serum-resistant.
      For the lowest concentration of chlorine (0.2 mg/l) tested, no killing of biofilm
      bacteria could be discerned, even after prolonged exposure to the agent. Although
      all the drinking water isolates were susceptible to aztreonam, cefepime,
      ceftazidime, ciprofloxacin, imipenem, meropenem, piperacillin-tazobactam, and
      polymyxin, the P. aeruginosa isolates were resistant to one or more antibiotics.
      The increasing prevalence of resistance in the isolates from environmental
      sources may have important therapeutic implications. A notable proportion of the
      P. aeruginosa isolates from drinking water were able to develop virulence
      factors, and the incidence of virulence properties was not statistically
      different among the three sources. A more extensive study of the virulence
      properties of this bacterium by toxic assays on animals should be explored. Still
      more interesting would be toxicity assays on immuno-deficient animals with
      isolates from drinking water in order to better understand the health risk these
      bacteria may present.

PMID- 18038253
TI  - Efficacy and safety of a combination of Sabal and Urtica extract in lower urinary
      tract symptoms--long-term follow-up of a placebo-controlled, double-blind,
      multicenter trial.
AB  - In an open-label extension of a randomized, double-blind clinical trial, the long
      term efficacy and tolerability of a fixed combination of 160 mg Sabal fruit
      extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule (PRO 160/120)
      were investigated in elderly men with moderate or severe lower urinary tract
      symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). Two hundred and
      fifty-seven patients were randomly treated with 2 x 1 capsule/day PRO 160/120 or
      placebo for 24 weeks, followed by a 24-week control period and a 48-week follow
      up period in which all patients received PRO 160/120. Efficacy measures included
      the assessment of LUTS [International Prostate Symptom Score ((I-PSS) self-rating
      questionnaire] and uroflow and sonographic parameters. Two hundred and nineteen
      subjects participated in the follow-up. Between baseline and end of observation
      (week 96) the I-PSS total score was reduced by 53% (P < 0.001), peak and average
      urinary flow increased by 19% (P < 0.001), and residual urine volume decreased by
      44% (P = 0.03). The incidence of adverse events during follow-up was one in 1,181
      treatment days; in only one event a causal relationship with intake of PRO
      160/120 could not be excluded. Treatment with PRO 160/120 thus provides a
      clinically relevant benefit over a period of 96 weeks.

PMID- 18038259
TI  - Proliferation-specific genes activated by Galpha(12): a role for PDGFRalpha and
      JAK3 in Galpha(12)-mediated cell proliferation.
AB  - Galpha(12), the alpha-subunit of G protein G12, is ubiquitously expressed and it
      has been identified as a putative "causative oncogene" of soft-tissue sarcomas.
      Overexpression of wild-type or GTPase-deficient mutant of Galpha(12)
      (Galpha(12)Q229L or Galpha(12)QL) leads to the oncogenic transformation of NIH3T3
      cells. Galpha(12)QL-tramsformed NIH3T3 cells show a distinct oncogenic phenotype
      defined by increased cell proliferation, anchorage-independent growth, reduced
      growth-factor dependency, attenuation of apoptotic signals, and neoplastic
      cytoskeletal changes. In this study, the genes contributing to the reduced growth
      factor dependency of Galpha(12)QL-NIH3T3 cells were identified by transcription
      profiling of serum-starved Galpha(12)QL-transformed NIH3T3 (Galpha(12)QL-NIH3T3)
      cells. Results from these studies indicate that Galpha(12)QL stimulates the
      expression of genes that promote cell growth. The increased expressions of growth
      promoting genes in Galpha(12)QL-NIH3T3 cells were validated by semiquantitative
      reverse transcription-polymerase chain reaction and immunoblot analyses. Further
      studies aimed at investigating the critical role of two of such upregulated
      genes, namely PDGFRalpha and JAK3, indicated that the inhibition of PDGFRalpha or
      JAK3 activity-attenuated Galpha(12)QL-mediated serum-independent cell
      proliferation. These studies point to possible novel autocrine and/or paracrine
      control mechanisms involving PDGFRalpha and JAK3 in Galpha(12)-mediated
      proliferation and oncogenesis.

PMID- 18038264
TI  - Use of experimental design in the optimisation of stir bar sorptive extraction
      followed by thermal desorption for the determination of brominated flame
      retardants in water samples.
AB  - A method for the determination of polybrominated diphenyl ethers (PBDEs) and
      polybrominated biphenyls (PBBs) in water samples is proposed. The method
      involving stir bar sorptive extraction (SBSE) and thermal desorption followed by
      gas chromatography coupled with mass spectrometry was optimised using statistical
      design of experiments. In the first place, the influence of different
      polydimethylsiloxane stir bars was studied. A Plackett-Burman design was chosen
      to estimate the influence of five factors on the efficiency of the SBSE process:
      desorption time (5-10 min), desorption temperature (250-300 degrees C),
      desorption flow (50-100 mL min(-1)), cryofocusing temperature (-130 to 40 degrees
      C) and vent pressure (0-12.8 psi). Afterwards, two central composite designs were
      used to find the optimal process settings that were applied to the optimisation
      of both desorption and extraction efficiency. In the case of the desorption
      parameters, long desorption times (10 min) and desorption flows lower than 70 mL
      min(-1) yielded the best signals for the majority of compounds. However,
      different behaviour among the analytes was observed for the vent pressure and we
      decided to fix it at an intermediate value (7 psi). In the case of extraction
      parameters, the sample volume and the addition of NaCl did not have a significant
      effect, while the addition of methanol yielded better extraction responses.
      Remarkable recovery (82-106%) and repeatability (less than 18%) were attained.
      Furthermore, excellent regression coefficients (r2 = 0.991-0.999) and low
      detection limits (1.1-6.0 ng L(-1)) were also achieved for the congeners studied.
      The proposed method was applied to the analyses of PBDEs and PBBs in waters from
      the Basque Country, Spain.

PMID- 18038266
TI  - Nosocomial pneumonia - are economical considerations important?

PMID- 18038265
TI  - Cortical silent period following TMS in a patient with supplementary sensorimotor
      area seizures.
AB  - The cortical silent period (CSP) following transcranial magnetic stimulation
      (TMS) was evaluated in a patient with a dysembrioplastic neuroepithelial tumor
      (DNET) in the lateral portion of the right superior frontal gyrus (SFG) who
      suffered from supplementary sensorimotor area (SSMA) seizures. CSP duration was
      shortened on the affected side. Ipsilateral alterations of motor cortex
      excitability with TMS in epileptogenic DNET located outside the PMA argue in
      favour of cortico-cortical connections to primary motor cortex from SSMA. This
      functional connectivity should be taken into consideration to better understand
      the pathophysiology of ictal motor manifestations.

PMID- 18038267
TI  - Characterization of typo-, regio-, and stereo-selectivities of babaco latex
      lipase in aqueous and organic media.
AB  - The unripe fruit of babaco (Vasconcellea x heilbornii; syn. Carica pentagona)
      contains a latex, similar to that in Carica papaya, which exhibits lipolytic
      activity. Herein, the regioselectivity, stereoselectivity and typoselectivity in
      both hydrolysis and acyltransfer reactions of babaco latex lipases were studied
      and compared to those of Carica papaya latex. In hydrolysis, both biocatalysts
      are 1,3-regioselective with ratios for 1,2-2,3-diacylglycerols/1,3-diacylglycerol
      of 6.5 and 21 for babaco and papaya, respectively. In contrast, papaya latex had
      a slight sn-3 stereopreference. Babaco latex displayed a higher activity on
      triacylglycerols with short chain and unsaturated fatty acids.

PMID- 18038268
TI  - Cloning and expression of glucose regulated protein 78 (GRP78) in Fenneropenaeus
      chinensis.
AB  - GRP78 (78 kDa glucose-regulated protein), also known as BiP (immunoglobulin heavy
      chain-binding protein), is an essential regulator of endoplasmic reticulum (ER)
      homeostasis because of its multiple functions in protein folding, ER calcium
      binding, and controlling of the activation of transmembrane ER stress sensors. In
      this report, we cloned the full length cDNA of GRP78 (FcGRP78) from Chinese
      shrimp Fenneropenaeus chinensis. This cDNA revealed a 2,325 bp with 1,968 bp open
      reading frame encoding 655 amino acids. This is the first reported GRP78 gene in
      Crustacea. The deduced amino acid sequence of FcGRP78 shared high identity with
      previously reported insect GRP78s: 86, 87 and 85% identity with GRP78s of
      Drosophila melanogaster, Aedes aegypti and Bombyx mori, respectively. Northern
      blot analysis shows that FcGRP78 is ubiquitously expressed in tissues of shrimp.
      Heat shock at 35 degrees C significantly enhanced the expression of FcGRP78 at
      the first hour, reached the maximum at 4 h post heat shock, dropped after that
      and resumed to the normal level until 48 h of post recovery at 25 degrees C.
      Additionally, differential expression of FcGRP78 was detected in haemocytes,
      hepatopancreas and lymphoid organ when shrimp were challenged by white spot
      syndrome virus (WSSV). We inferred that FcGRP78 may play important roles in
      chaperoning, protein folding and immune function of shrimp.

PMID- 18038269
TI  - Lysophosphatidic acid-induced interleukin-1 beta expression is mediated through
      Gi/Rho and the generation of reactive oxygen species in macrophages.
AB  - Lysophosphatidic acid (LPA), a low-molecular-weight lysophospholipid enriched in
      platelets and mildly oxidized low-density lipoproteins, is known to regulate
      inflammation and atherosclerosis by binding to its cognate receptors. In this
      study, we reported that LPA upregulated interleukin-1 beta (IL-1 beta) expression
      in mouse J774A.1 macrophages. By using pharmacological inhibitors, it was
      suggested that G(i)/Rho activation and subsequent reactive oxygen species (ROS)
      production were involved in IL-1 beta induction. In addition, IL-1 beta induction
      by LPA was also observed in human primary macrophages. In summary, LPA is
      involved in the processes of inflammation by affecting macrophage behavior.

PMID- 18038271
TI  - Cardioprotection of neonatal heart using normothermic hyperkalaemia: the
      importance of delivery and terminal cardioplegia.
AB  - Cardioprotection of immature hearts remains controversial and largely based on
      the use of hypothermic cardioplegia. Recent clinical trials in pediatric open
      heart surgery suggest that normothermic cardioplegic arrest is also
      cardioprotective. However, the advantages of using normothermic cardioplegia
      delivered as single- or multi-dose with or without terminal cardioplegia are
      unknown. This work investigates the efficacy of these techniques and the
      mechanism(s) underlying their protective effect. Neonatal (7-10 days) rabbit
      hearts in a working mode were exposed to normothermic global ischemia (60 or 90
      min) protected with one of the following cardioplegic (hyperkalaemic buffer)
      protocols: single-dose, multi-dose infused every 30 min, single-dose or multi
      dose with terminal cardioplegia. The extent of functional recovery (e.g., aortic
      and coronary flow), ischemic stress (e.g., myocardial ATP, lactate) and
      reperfusion injury (lactate dehydrogenase (LDH) release) were assessed. Recovery
      following 60 min global ischemia was improved (p < 0.05) by single-dose and multi
      dose cardioplegic delivery (from 5% to 60% and 80%, respectively). Improved
      recovery was augmented by 2 min terminal cardioplegia (to 90% and 97% for single
      dose and multi-dose, respectively). Extending ischemia to 90 min with single-dose
      resulted in 0% recovery that was not improved by 2 min terminal cardioplegia.
      However, 5 min (not 10 min) terminal cardioplegia significantly improved recovery
      (32%). Multi-dose followed by 5 min terminal cardioplegia resulted in full
      recovery. Cardioprotective interventions were associated with a reduction in LDH
      release and attenuated changes in myocardial metabolites. During normothermic
      cardioplegic arrest of neonatal heart: (i) multi-dose is superior to single-dose;
      (ii) terminal cardioplegia confers additional protection to single-dose and multi
      dose; and (iii) protection is likely to be due to metabolic preservation.

PMID- 18038270
TI  - Human tau protein forms complex with PrP and some GSS- and fCJD-related PrP
      mutants possess stronger binding activities with tau in vitro.
AB  - Microtubule associated protein tau is considered to play roles in some types of
      human transmissible spongiform encephalopathies (TSE). In this study, the full
      length and several truncated human tau proteins were expressed from E. coli and
      purified. Using GST pull down, co-immunoprecipitation assay and tau-coated ELISA,
      the molecular interaction between tau protein and PrP was confirmed in the
      context of the full-length human tau. The N terminus (amino acids 1-91) and
      tandem repeats region (amino acids 186-283) of tau protein were responsible for
      the interaction with PrP. The octapeptide repeats within PrP directly affected
      the binding activity of PrP with tau. GSS-related mutant PrP102L and fCJD-
      related mutants with two and seven extra octarepeats showed more active binding
      capacity with tau than wild-type PrP. The molecular interactions between PrP and
      tau protein highlight a potential role of tau in the biological function of PrP
      and the pathogenesis of TSE.

PMID- 18038272
TI  - Methylmercury exposure associated with reduced productivity in common loons.
AB  - Methylmercury can impair the reproduction of fish-eating wildlife. We measured
      lake pH, mercury (Hg) concentrations in small fish, blood Hg levels in adult
      male, female and juvenile common loons, and loon productivity from 120 lakes in
      Wisconsin, USA and New Brunswick and Nova Scotia, Canada (Maritimes). Mean lake
      pH was higher in Wisconsin than in the Maritimes. Body masses of adult loons and
      Hg concentrations in the blood of loons and in small fish were greater in the
      Maritimes. Hg levels in fish increased with lake acidity. Abundance of small fish
      increased in acidic lakes in the Maritimes. Blood Hg concentrations in adult and
      juvenile loons decreased with lake pH and increased with Hg levels in fish prey.
      Hg levels in male, female and juvenile loons were 22, 16 and 2.3 times greater
      than those in small fish. Loon Hg exposure, measured either as Hg levels in
      female loon blood or in fish prey, appeared to impose an upper limit on loon
      productivity. Loon productivity decreased as Hg exposure increased. Quantile
      regression analysis indicated that maximum observed loon productivity dropped 50%
      when fish Hg levels were 0.21 ug/g (wet wt), and failed completely when fish Hg
      concentrations were 0.41 ug/g.

PMID- 18038273
TI  - Risedronate for prevention of bone mineral density loss in patients receiving
      high-dose glucocorticoids: a randomized double-blind placebo-controlled trial.
AB  - This 6-month randomized double-blind placebo-controlled trial shows that
      risedronate is well tolerated and effective in improving lumbar spine BMD and
      reducing loss of BMD at the hips in patients receiving high-dose prednisolone.
      INTRODUCTION: Bisphosphonates have proven benefits in patients receiving chronic
      low-dose glucocorticoids. However, whether they are effective in preventing bone
      mineral density (BMD) loss during periods of high-dose glucocorticoid treatment
      is unclear. The objective of this paper is to study the efficacy of risedronate
      in preventing bone mineral density (BMD) loss in users of high-dose
      glucocorticoids. METHODS: Adult patients with medical diseases treated with high
      dose prednisolone (>0.5 mg/kg/day) were randomized to receive risedronate (5
      mg/day) or placebo for 6 months in a double-blind manner, along with elemental
      calcium (1,000 mg/day). Changes in BMD were studied. RESULTS: One hundred and
      twenty patients were recruited (82 women, age 42.8 +/- 14.3 years, 63%
      corticosteroid-naive, 30% women postmenopausal) and 103 completed the study.
      Baseline clinical characteristics and BMD were similar in the risedronate and
      placebo groups. At 6 months, a significant gain in spinal BMD was observed in the
      risedronate group (+0.7 +/- 0.3%; p = 0.03) but a drop was detected in the
      placebo group (-0.7 +/- 0.4%; p = 0.12). After adjustment for baseline BMD, age,
      gender, body mass index and cumulative prednisolone dosages, the inter-group
      difference in spinal BMD remained significant (1.4%; p = 0.006). Both groups had
      a significant drop in hip BMD, but the magnitude was greater in the placebo arm (
      0.8 +/- 0.4% in risedronate versus -1.3 +/- 0.5% the in placebo). No new
      fractures developed. Subgroup analysis of corticosteroid-naive patients yielded
      similar results. Upper gastrointestinal adverse events were numerically more
      frequent in the risedronate group. CONCLUSIONS: Risedronate improves spinal BMD
      in users of high-dose glucocorticoids.

PMID- 18038274
TI  - Antitumour effect of combination treatment with Sabarubicin (MEN 10755) and cis
      platin (DDP) in human lung tumour xenograft.
AB  - PURPOSE: Sabarubicin (MEN 10755), a new disaccaride anthracycline, has shown
      greater efficacy than Doxorubicin in a large panel of preclinical models and now
      it is in phase II clinical trials. Its promising antitumour activity promoted
      considerable interest to combine Sabarubicin with other antitumour agents. Thus,
      the purpose of this study was to evaluate in vitro cytotoxic effects and in vivo
      antitumour activities produced by the combination of Sabarubicin and cisplatin
      (DDP). METHODS: The antitumour effect of Sabarubicin and DDP association was
      investigated, in vitro and in vivo, in preclinical models of lung cancer i.e.:
      the non-small cell lung carcinoma (NSCLC) H460 and the small-cell lung carcinoma
      (SCLC) GLC4 in terms of synergism, additivity or antagonism in order to establish
      the best schedule for the combined treatment. Further, the correlation between
      antitumour activity and the pharmacokinetic parameters of the studied combination
      was also evaluated. RESULTS: The drug combination in vitro was in general more
      cytotoxic than the single drug alone, indicating the presence of a synergistic
      effect in both tumour cell lines. Also, in the xenograft experiments a superior
      antitumoral effect was observed when Sabarubicin was combined with DDP. The
      antitumour efficacy of Sabarubicin (6 mg/kg q4d x 5) combined with DDP (6 mg/kg
      q4d x 3) greatly depended on the schedule of administration. In H460 tumour line,
      the sequential combination was more effective than the simultaneous
      administration of the two agents, although the antitumour efficacy was not
      dependent on the sequence of combination. On the other hand, a strong sequence
      dependent effect was observed when Sabarubicin was combined with DDP in SCLC,
      GLC4. In particular, the highest value of LCK = 6.7 was obtained when
      administration of DDP followed by 24 h that of Sabarubicin. Pharmacokinetics of
      Sabarubicin in combination with DDP was evaluated at 6 mg/kg for both drugs with
      different sequential schedule. The experimental data showed no evidence for
      pharmacokinetics drug-drug interaction. CONCLUSION: These preclinical results
      indicate the potential for a strong antitumour activity in lung tumours of the
      combination Sabarubicin and DDP. In particular, in SCLC the best response should
      be given by a sequence with administration of Sabarubicin followed 24 h later by
      that of DDP. Clinical trials based on these results are ongoing.

PMID- 18038276
TI  - Novel sound production through contingency learning in the Pacific walrus
      (Odobenus rosmarus divergens).
AB  - Walruses (Odobenus rosmarus) are highly vocal amphibious mammals with a range of
      anatomical specializations that can provide plasticity to their sound emissions.
      The objective of this descriptive study was to determine whether contingency
      learning could be used to increase variability and induce novelty in the acoustic
      behavior of walruses. The subjects were two twelve-year-old captive walruses, a
      male and a female that had previously been conditioned using food reinforcement
      to produce several specific sounds in response to different discriminative cues.
      In the current task, these individuals were encouraged to produce novel sounds
      and novel sound combinations in air by withholding reinforcement for sounds
      previously emitted in a given session and providing reinforcement only for
      qualitative differences in emitted sounds. Following training in air, the
      walruses were tested under water with the same reinforcement contingency. The
      subjects responded as they had done in air, by varying their underwater sound
      emissions until reinforcement was provided. Many of the sounds and sound
      combinations produced by the subjects during underwater testing were quite
      different from those produced during training in air and those produced under
      water during baseline observations. Both the male and female spontaneously
      emitted knocks and soft bells which are components of the songs known to be
      emitted by mature male walruses during the breeding season. The finding that
      reinforced variability can induce creativity in sound production is consistent
      with recent experiments on budgerigar birds showing that vocal topographies, like
      motor responses, may be influenced by contingency learning.

PMID- 18038277
TI  - An investigation of douching practices in the botanicas of the Bronx.
AB  - Douching is a common practice in women and has been associated with adverse
      health outcomes. In order to explore douching products and practices we conducted
      qualitative interviews in ten botanicas (stores that provide healing and
      spiritual services to immigrant communities) located in New York City. We
      interviewed 15 people, 14 of whom were botanica owners and employees and ten of
      whom were women. We found that douching was not easily separated from the more
      holistic concerns of botanica customers involving health, well-being and
      spirituality. These issues included abortion, infertility, menopause, the
      prevention and treatment of infections, sexuality, cleanliness, hygiene and
      relationship issues. The vagina was seen as a sensitive, even vulnerable part of
      the body, not clearly distinguished from other female organs. A variety of
      products were used in the vagina in the form of creams, douches, suppositories,
      baths and herbal steaming of the urogenital area. Alum, an astringent, was used
      for the purposes of vaginal tightening to enhance sexual pleasure for the
      partner, to make the vagina 'younger', or to hide evidence of infidelity.
      Botanicas are part of a complex healing system with conceptual models different
      from those of allopathic medicine. These models may not be unique to the
      botanicas.

PMID- 18038278
TI  - Secrecy, disclosure and accidental discovery: perspectives of diaphragm users in
      Mombasa, Kenya.
AB  - The diaphragm is receiving renewed attention as a promising female-controlled
      method of preventing HIV and other sexually-transmitted infections. It is
      anticipated that female-controlled technologies will reduce women's biological
      susceptibility and assist in counteracting their sociocultural vulnerability to
      HIV. Understanding the subjective experiences of diaphragm users in different
      settings has the potential to inform the development and promotion of such
      methods. This paper explores the perspectives of female sex workers and women
      attending sexual and reproductive health services in Mombasa, Kenya. Data are
      reported from focus group discussions and in-depth interviews with women and men,
      following a prospective study investigating diaphragm continuation rates over six
      months. Discussions highlighted covert use of the diaphragm, during sex work or
      with casual partners, and coital independence as favourable attributes. These
      features were especially pronounced compared with male condoms. Few difficulties
      with diaphragm use were reported, although its insertion and removal occasionally
      presented problems. Many women--especially those in long term partnerships-
      wished to disclose its use but found the disclosure process highly problematic.
      Accidental discovery often resulted in partner conflict. Although future uptake
      of the diaphragm may be high in this setting, its use may be limited to certain
      types of relationships and relationship context.

PMID- 18038279
TI  - The limits of behaviour change theory: condom use and contexts of HIV risk in the
      Kolkata sex industry.
AB  - This paper uses ethnographic data from a sex workers' HIV project in India to
      consider the appropriateness of individual, social/group and structural theories
      of health behaviour when applied to HIV-prevention initiatives. Existing theories
      are critiqued for their modernist representation of behaviour as determined by
      individual rational decision-making processes or by external structural forces,
      with inadequate recognition being given to the roles that human agency,
      subjective meaning and local context play in everyday actions. Analysis of sex
      workers' accounts of their sexual practices suggests that existing theories of
      health behaviour can only partially account for sexual behaviour change
      retrospectively and that they have limited predictive value with respect to the
      outcomes of individual sexual encounters. Our data show that these outcomes were,
      in fact, highly context dependent, while possibilities for action were ultimately
      strongly constrained by structural forces. Findings suggest that interventions
      need to adopt an integrated, structurally-oriented approach for promoting safer
      sexual practices in sex work settings. Recognising that no one model of health
      behaviour is likely to be adequate in explaining or predicting behaviour change
      encourages responsiveness to local people's agency, recognises the different
      (health- and non-health-related) registers of risk with which people operate and
      encourages flexibility according to local contingencies and contexts.

PMID- 18038280
TI  - HIV risk among long-haul truckers in the USA.
AB  - Long-haul truck driving has been associated with HIV risk in developing countries
      but little research to date has considered whether truckers in the USA may also
      be at elevated risk for HIV and other STIs. This multi-method qualitative study
      explored HIV-risk factors among regional and cross-country truck drivers who were
      based in the southeastern USA. Data collection methods included focus groups
      conducted at company hubs and over Citizen's Band (CB) radio, and key informant
      interviews. Results indicated that sexual opportunities and risks are greater for
      long-haul drivers who often travel for long periods without returning home and
      who may engage in 'highway sex' in the absence of a regular home-life. Structural
      factors that have reduced drivers' autonomy, sexual risk taking and free time
      while traveling include recent trucking regulations, electronic surveillance and
      industry-wide trends emphasizing speed and efficiency. Other factors, such as
      age, experience, type of employment and type of route also play a role. Further
      research is needed to determine if these qualitative findings can be quantified
      in population-based studies that also include biomarker and incidence data.

PMID- 18038281
TI  - Operationalising 'sexual orientation' in routine data collection and equality
      monitoring in the UK.
AB  - New legal provisions and regulatory practices in the UK have afforded protection
      against discrimination for sexual orientation minorities and conferred rights
      similar to those of heterosexually partnered couples. In addition, sexual
      orientation has been recognised as one of the main equality strands in new
      equality legislation and equality governance. Government departments and
      statutory and other organisations now face the need to collect equal
      opportunities and other data on these groups to monitor compliance. However,
      there has been little track record in the UK of collecting data on this
      dimension, resulting in issues of definition, categorisation, sample size and
      potential measurement error having to be addressed from a negligible evidence
      base. Limited survey data indicate significant problems relating to item non
      response and misreporting, reflecting wider concerns about the sensitivity of the
      data and disclosure. Given that sexual orientation is on track to be mainstreamed
      in the context of workforce recruitment and service delivery, a strategy across
      government and other sectors is needed to pool expertise and establish a shared
      evidence base and stock of good practice.

PMID- 18038282
TI  - From closet to heterotopia: a conceptual exploration of disclosure and 'passing'
      among heterosexuals living with HIV.
AB  - This paper explores how experiences of disclosure and passing among heterosexuals
      living with HIV in Australia can be meaningfully conceptualised beyond
      therapeutic discourses and habitual metaphors. It engages in a dialogue between
      qualitative research material, HIV disclosure literature and theory. It is first
      argued that an emphasis on the therapeutic value of disclosure in much of the
      literature obscures the complexities of HIV stigma as socially produced and
      lived. Next, the paper considers the concepts of 'the closet' and 'coming out',
      which have become short-hand for a range of social stigmas. Although parallels
      are found between the productive effects of the closet and the research material,
      the idea of 'coming out' fails to capture the cultural context of HIV in
      Australian heterosexual society. This raises questions about the contemporary
      tendency to invoke the closet as a presumedly universal metaphor. Foucault's idea
      of heterotopia is proposed as an alternative way of conceptualising the lived
      worlds of disclosure and passing in this research study, with the hope of opening
      out future discussion and theorising.

PMID- 18038283
TI  - Marriage is not a safe place: heterosexual marriage and HIV-related vulnerability
      in Indonesia.
AB  - This paper examines the link between heterosexual marriage and women's
      vulnerability to HIV in Indonesia. In this country, gender relations are
      currently dominated by traditional beliefs and practices and by religious
      morality. Data for the current study were collected by means of documentary
      analysis and archival research as well as by means of expert informant
      interviews. Findings suggest that traditional practices such as polygamy, early
      marriage and contract marriage (mut'a) play an important role in enhancing
      women's likelihood of acquiring HIV within the Indonesian context.

PMID- 18038275
TI  - Alzheimer disease models and human neuropathology: similarities and differences.
AB  - Animal models aim to replicate the symptoms, the lesions or the cause(s) of
      Alzheimer disease. Numerous mouse transgenic lines have now succeeded in
      partially reproducing its lesions: the extracellular deposits of Abeta peptide
      and the intracellular accumulation of tau protein. Mutated human APP transgenes
      result in the deposition of Abeta peptide, similar but not identical to the Abeta
      peptide of human senile plaque. Amyloid angiopathy is common. Besides the
      deposition of Abeta, axon dystrophy and alteration of dendrites have been
      observed. All of the mutations cause an increase in Abeta 42 levels, except for
      the Arctic mutation, which alters the Abeta sequence itself. Overexpressing wild
      type APP alone (as in the murine models of human trisomy 21) causes no Abeta
      deposition in most mouse lines. Doubly (APP x mutated PS1) transgenic mice
      develop the lesions earlier. Transgenic mice in which BACE1 has been knocked out
      or overexpressed have been produced, as well as lines with altered expression of
      neprilysin, the main degrading enzyme of Abeta. The APP transgenic mice have
      raised new questions concerning the mechanisms of neuronal loss, the accumulation
      of Abeta in the cell body of the neurons, inflammation and gliosis, and the
      dendritic alterations. They have allowed some insight to be gained into the
      kinetics of the changes. The connection between the symptoms, the lesions and the
      increase in Abeta oligomers has been found to be difficult to unravel.
      Neurofibrillary tangles are only found in mouse lines that overexpress mutated
      tau or human tau on a murine tau -/- background. A triply transgenic model
      (mutated APP, PS1 and tau) recapitulates the alterations seen in AD but its
      physiological relevance may be discussed. A number of modulators of Abeta or of
      tau accumulation have been tested. A transgenic model may be analyzed at three
      levels at least (symptoms, lesions, cause of the disease), and a reading key is
      proposed to summarize this analysis.

PMID- 18038286
TI  - Sequential activation of multiple grounding pads reduces skin heating during
      radiofrequency tumor ablation.
AB  - PURPOSE: Radiofrequency (RF) tumor ablation has become an accepted treatment
      modality for tumors not amenable to surgery. Skin burns due to ground pad heating
      may become a limiting factor for further increase in ablation zone dimensions and
      generator power. We investigated a method were groups of ground pads are
      sequentially activated to reduce skin heating. METHODS: We compared conventional
      operation (i.e. simultaneous connection of all pads) to sequentially switched
      activation of the pads where different pad combinations are active for periods of
      approximately 0.3 - 8 s. The timing during sequential activation was adjusted to
      keep the leading edge temperature equal between the pads. We created Finite
      Element Method computer models of three pads (5 x 5 cm, 1 cm apart) placed in
      line with the RF electrode on a human thigh to determine differences in tissue
      heating during simultaneous and sequential ground pad activation. We performed
      experiments with three ground pads (5 x 10 cm, 4 cm apart) placed on a tissue
      phantom (1.5 A, 12 min) and measured pad surface and leading edge temperatures.
      RESULTS: Temperature rise below the leading edge for proximal, middle and distal
      ground pad in relation to active electrode location was 5.9 degrees C +/- 0.1
      degrees C, 0.8 degrees C +/- 0.1 degrees C and 0.3 degrees C +/- 0.1 degrees C
      for conventional operation, and 3.3 degrees C +/- 0.1 degrees C, 3.4 degrees C +/
      0.2 degrees C and 3.4 degrees C +/- 0.2 degrees C for sequentially activated
      operation in the experiments (p < 0.001). CONCLUSION: Sequential activation of
      multiple ground pads resulted in reduced maximum tissue temperature. This may
      reduce the incidence of ground pad burns and may allow higher power RF
      generators.

PMID- 18038287
TI  - Winner of the "New Investigator Award" at the European Society of Hyperthermia
      Oncology Meeting 2007. The HYPERcollar: a novel applicator for hyperthermia in
      the head and neck.
AB  - The purpose of this work was to define all features, and show the potential, of
      the novel HYPERcollar applicator system for hyperthermia treatments in the head
      and neck region. The HYPERcollar applicator consists of (1) an antenna ring, (2)
      a waterbolus system and (3) a positioning system. The specific absorption rate
      (SAR) profile of this applicator was investigated by performing infra-red
      measurements in a cylindrical phantom. Mandatory patient-specific treatment
      planning was performed as an object lesson to a patient with a laryngeal tumour
      and an artificial lymph node metastasis. Comfort tests with healthy volunteers
      have revealed that the applicator provides sufficient comfort to maintain in
      treatment position for an hour: the standard hyperthermia treatment duration in
      our centre. By phantom measurements, we established that a central focus in the
      neck can be obtained, with 50% iso-SAR lengths of 3.5 cm in transversal
      directions (x/y) and 9-11 cm in the axial direction (z). Using treatment planning
      by detailed electromagnetic simulations, we showed that the SAR pattern can be
      optimised to enable simultaneous encompassing of a primary laryngeal tumour and a
      lymph node metastasis at the 25% iso-SAR level. This study shows that the
      applicator enables a good control, and sufficient possibilities for optimisation,
      of the SAR pattern. In an ongoing clinical feasibility study, we will investigate
      the possibilities of heating various target regions in the neck with this
      apparatus.

PMID- 18038288
TI  - Computational feasibility of deformable mirror microwave hyperthermia technique
      for localized breast tumors.
AB  - PURPOSE: Computational feasibility of a new non-invasive microwave hyperthermia
      technique that employs dual deformable mirror is investigated using simplified
      computational tools and anatomically realistic breast models. MATERIALS AND
      METHODS: The proposed technique employs two pairs of electromagnetic sources and
      continuously deformable mirrors to focus the electromagnetic radiation at the
      target site for hyperthermia. The mirror functions like a continuum of radiating
      elements that offer effective scan coverage inside the breast with efficient
      field focusing at the target location. The electric field focusing and
      temperature mapping in the two-dimensional numerical simulations are investigated
      using wave propagation and bio-heat transfer models respectively. The method of
      moments, a popular numerical simulation tool, is used to model the electric field
      maintained by the deformable mirrors for continuous wave excitation. The
      electromagnetic (EM) energy deposited by the mirrors is used in the steady state
      bio-heat transfer equation to quantify the temperature distribution inside two
      dimensional anatomically realistic breast models. RESULTS: Feasibility of the
      proposed technique is evaluated using numerical breast models derived from
      magnetic resonance images of patients with variation in breast density, age and
      pathology. CONCLUSIONS: The computational study indicates preferential EM energy
      deposition and temperature elevation inside tumor tissue with minimum collateral
      damage to the neighboring normal tissues. Simulation results obtained for the
      magnetic resonance (MR) breast data appear promising and indicate the merit in
      pursuing the investigation using 3D computational models.

PMID- 18038289
TI  - Antitumor effect of whole body hyperthermia with alpha-galactosylceramide in a
      subcutaneous tumor model of colon cancer.
AB  - AIM: Whole body hyperthermia (WBH) has been used clinically as an adjunct to
      radio- and chemotherapy in patients with various cancers. Recently, it has been
      reported that an activation of the immune system has recently been reported as a
      possible contributor to the therapeutic effects of WBH. Conversely, the
      glycolipid alpha-galactosylceramide (alpha-GalCer) is recognized by natural
      killer (NK) T cells together with the monomorphic MHC-like antigen, CD1d, in mice
      and humans. This study investigated the antitumor effects of WBH combined with
      alpha-GalCer in a mouse subcutaneous tumor model of colon cancer. METHODS:
      Colon26 cells were inoculated subcutaneously into male BALB/c mice to establish
      subcutaneous tumor. Colon26-bearing mice were treated with WBH using far infrared
      rays three times/week. Rectal temperature was maintained for 60 min at 41 degrees
      C. In some experimental groups, alpha-GalCer was intraperitoneally injected
      before WBH. We investigated the therapeutic effects of WBH, alpha-GalCer and
      combined therapy. RESULTS: (1) Compared with controls, WBH alone resulted in
      significant inhibition of tumor growth. (2) No inhibitory effect on tumor growth
      was seen with alpha-GalCer. (3) The combination of WBH and alpha-GalCer showed
      significant inhibition of tumor growth and prolongation of survival. (4) Serum
      IFN-gamma increased after 3 h and returned to basal levels by 24 h after alpha
      GalCer administration. (5) CTL activity was enhanced following combination
      therapy with WBH and alpha-GalCer. CONCLUSION: WBH showed antitumor effects in a
      mouse subcutaneous tumor model of colon cancer. Addition of alpha-GalCer
      increased the efficacy of WBH, probably via enhancement of immune response.

PMID- 18038291
TI  - World Health Organization Study Group on Interprofessional Education and
      Collaborative Practice.

PMID- 18038290
TI  - The new vascular disrupting agent combretastatin-A1-disodium-phosphate (OXi4503)
      enhances tumour response to mild hyperthermia and thermoradiosensitization.
AB  - PURPOSE: The aim of this study was to investigate the anti-cancer effect of the
      novel vascular disrupting agent (VDA), combretastatin-A1-disodium-phosphate
      (OXi4503), when combined with mild hyperthermia and/or radiation. MATERIALS AND
      METHODS: A C3H mammary carcinoma was grown subcutaneously in the rear right foot
      of female CDF1 mice, and treated when a volume of 200 mm(3) was reached. OXi4503
      was administered intra-peritoneally at variable doses. Hyperthermia was
      administered locally to the tumour-bearing foot using a thermostat-controlled
      water bath. Radiation treatment was performed locally using a conventional X-ray
      machine. Tumour response was assessed with either a tumour growth time or a
      tumour control assay. RESULTS: The optimal delay between administration of 50
      mg/kg of OXi4503 and hyperthermia was found to be 3 hours. The linear
      relationship between tumour growth time (TGT) and heating time at a specific
      temperature resulted in slope values between -0.003 days/min and 0.09 days/min at
      temperatures between 40 degrees C and 42.5 degrees C. When combined with OXi4503
      this was significantly increased to 0.008 days/min and 0.03 days/min at
      temperatures between 39.5 degrees C and 41 degrees C, respectively. Above 41
      degrees C, combined treatment did not result in significantly greater slope
      values. The radiation dose required to control 50% of the tumours (TCD50) was 52
      Gy. Combining radiation with either heat treatment at 41.5 degrees C for 1 hour
      or OXi4503 reduced the TCD50 to 47 Gy and 41 Gy, respectively. Combining
      radiation with heat and OXi4503 further reduced the TCD50 to 37 Gy. CONCLUSIONS:
      OXi4503 is a highly potent VDA, which is capable of significantly enhancing the
      anti-cancer effect of mild hyperthermia. Mild temperature
      thermoradiosensitization was also enhanced.

PMID- 18038292
TI  - Theory and practice in interprofessional ethics: a framework for understanding
      ethical issues in health care teams.
AB  - Interprofessional teamwork is an essential and expanding form of health care
      practice. While moral issues arising in teamwork relative to the patient have
      been explored, the analysis of ethical issues regarding the function of the team
      itself is limited. This paper develops a conceptual framework for organizing and
      analyzing the different types of ethical issues in interprofessional teamwork.
      This framework is a matrix that maps the elements of principles, structures, and
      processes against individual, team, and organizational levels. A case study is
      presented that illustrates different dimensions of these topics, based on the
      application of this framework. Finally, a set of conclusions and recommendations
      is presented to summarize the integration of theory and practice in
      interprofessional ethics, including: (i) importance of a framework, (ii)
      interprofessional ethics discourse, and (iii) interprofessional ethics as an
      emerging field. The goal of this paper is to begin a dialogue and discussion on
      the ethical issues confronting interprofessional teams and to lay the foundation
      for an expanding discourse on interprofessional ethics.

PMID- 18038293
TI  - Facilitating interprofessional learning about human rights in public health
      contexts: challenges and strategies.
AB  - Occasions when public health practitioners engage in professional learning
      increasingly involve them in encounters with (a) concepts that originate from
      unfamiliar disciplines and that may be multidisciplinary, complex and sometimes
      contested, (b) colleagues who have different discipline and profession
      backgrounds, and (c) modes of learning and teaching that are unfamiliar. While
      these factors can enhance both the processes and products of learning, they can
      also present significant challenges when those learning occasions are designed
      and facilitated. Drawing on our own reflected-on experience of working in such
      contexts and a body of related literature, we elaborate on these interrelated
      challenges and propose three strategies that can help address them. The
      strategies entail encouragement and support for establishing common commitments
      and values, perspective-taking and self-reflexivity, conversation and
      storytelling. Specific examples of challenges and strategies are derived, in
      particular, from a learning agenda associated with the mainstreaming of a human
      rights approach to public health. That agenda requires practitioners to
      understand the concept of human rights, appreciate its relevance for public
      health work and be capable of integrating a human right perspective into their
      day-to-day work.

PMID- 18038294
TI  - Patient narratives: the potential for "patient-centred" interprofessional
      learning?
AB  - The central theme of the paper is concerned with the educational potential that
      patient narratives may hold for improving patient-centred interprofessional care.
      It follows the processes of a research project that was required to provide an
      educational intervention in a multiprofessionally-staffed stroke rehabilitation
      ward. It discusses the evolution of the project, focusing on the ways in which
      patient narratives were constructed, the purposes they served, and the responses
      of professionals to the narratives in subsequent workshops. Along the way, the
      paper reflects on the responses of patients that problematise the notion of
      "patient-centred" care. Together with the responses of professionals to the
      narratives, the paper raises questions about the obstacles to and possibilities
      for such care.

PMID- 18038295
TI  - Universities preparing health professionals for the 21st century: can something
      new come out of the traditional establishment?
AB  - To address clinical education in chronic disease management, the University of
      Alberta partnered with the local health authority to develop interprofessional
      team placements in diabetes chronic disease management. The objectives were to
      determine a meaningful and sustainable approach to interprofessional team
      placements. Pre-licensure students from medicine, nursing, nutrition and pharmacy
      participated in a project-based team experience designed to increase their
      discipline-specific knowledge of diabetes while enhancing their team process
      skills. Quantitative and qualitative research methods were used to evaluate
      project implementation and student outcomes. The majority of students reported
      learning "a great deal" about the roles of other health professionals and
      knowledge regarding the management of diabetes from the perspective of other
      health disciplines. However, several key learning outcomes were not fully
      accomplished; to enhance student's interprofessional team skills, increase their
      knowledge of interprofessional team functions and learn how to modify team
      function in a clinical setting. Creativity concerning relevant projects, varying
      settings, and differing models of service delivery should be encouraged, and
      flexibility within the project and process is essential for self-directed
      learning of student teams. New models of interprofessional clinical education,
      such as the chronic disease management model used in this study, have potential,
      if supported by the shift in health science programs culture.

PMID- 18038296
TI  - Providing clinical services for a diverse population: views on training of child
      and adolescent mental health practitioners.
AB  - The aim of this study was to explore what professionals working in a child and
      adolescent mental health service (CAMHS) thought of provision of mental health
      services to diverse groups and what their training needs might be. Semi
      structured interviews were undertaken and audiotaped with 17 CAMHS professionals.
      The tapes were transcribed and the data analysed using thematic analysis. The
      findings show no discernible pattern between different professional groups within
      the sample, although this is limited by the sample size and is perhaps not
      surprising given the common professional context. Just over half the participants
      perceived cultural diversity as equating with ethnic diversity. Staff thought
      diversity influenced service provision through access; communication; perceptions
      that different communities hold about mental health; perceptions that different
      communities hold about mental health services; and service factors. Staff were
      not clear about their own training needs and identified that training to date had
      not been entirely satisfactory. Staff openness may present an ideal opportunity
      to start dialogues with staff and community groups about how best services can be
      provided for an increasing diverse population of children and families.

PMID- 18038297
TI  - Interprofessional information work: innovations in the use of the chart on
      internal medicine teams.
AB  - An abundance of evidence suggests that communication in interprofessional
      healthcare teams is a complex endeavour. Even relatively simple communication
      processes involving information work - the gathering, storage, retrieval and
      discussion of patient information - may be fraught with pitfalls, and yet teams
      manage to conduct their daily information work, often with a high degree of
      effectiveness. In this article, we explore one commonplace dimension of
      information work - the use of patient charts to foster collaborative decision
      making and care enactment - towards building an elaborated understanding of how
      teams innovate in the face of daily complexities in their information work
      processes. Drawing on results from an ethnographic study of team communication in
      two internal medicine inpatient wards, we describe the nature and use of patient
      charts, analyze recurrent problems, and explore adaptive strategies for carrying
      on team information work in the face of daily barriers.

PMID- 18038298
TI  - Therapists' experiences and perceptions of teamwork in neurological
      rehabilitation: critical happenings in effective and ineffective teamwork.
AB  - This paper reports the second part of an exploratory study into occupational
      therapists' and physiotherapists' perceptions and experiences of teamwork in
      neurological rehabilitation: the factors that were thought to influence effective
      and ineffective teamwork, and the meaning behind effective and ineffective
      teamwork in neurological rehabilitation. The study was undertaken through semi
      structured interviews of 10 therapists from three different neurological
      rehabilitation teams based in the United Kingdom, and used the critical incident
      technique. Through analysis of the data, several main themes emerged regarding
      the perceived critical happenings in effective and ineffective teamwork. These
      were: team events and characteristics, team members' characteristics, shared and
      collaborative working practices, communication, specific organizational
      structures, environmental, external, and patient and family-related factors.
      Effective and ineffective team-work was perceived to impact on a number of
      levels: having implications for the team, the patient, individual team members,
      and the neurological rehabilitation service. The study supported the perceived
      value of team work within neurological rehabilitation. It also indicated the
      extensive and variable factors that may influence the team-working process as
      well as the complex and diverse nature of the process.

PMID- 18038299
TI  - Common training for students at the academic health centre.

PMID- 18038300
TI  - Interprofessional education online: the BMJ Learning experience.

PMID- 18038307
TI  - Editorial: Pathology in its fortieth year.

PMID- 18038308
TI  - Clinical and pathological features of eosinophilic oesophagitis: a review.
AB  - Eosinophilic oesophagitis (EOE) is a newly described clinicopathological entity
      that is being diagnosed with increasing frequency both in children and in adults.
      It is presumed to be an atopic disease involving both immediate and delayed-type
      hypersensitivity to inhaled and ingested allergens. Because of the reflux-type
      symptomatology, it is commonly misdiagnosed and treated as severe gastro
      oesophageal reflux disease (GORD) before an appropriate diagnosis is made.
      Pathologically, EOE is an inflammatory disorder with a predominantly eosinophilic
      infiltrate that is unresponsive to acid suppression therapy. The diagnosis of
      this disease requires histological confirmation with oesophageal biopsy specimens
      showing an intense eosinophilic infiltration. Although precise criteria or a
      specific cutoff point for the diagnosis of eosinophilic oesophagitis have not
      been established, many authors suggest that one high-power field with >20
      eosinophils or multiple high-power fields with >15 eosinophils, together with
      clinical and endoscopic findings, should be sufficient for diagnosis. Recognition
      of EOE and differentiation from GORD are important, since allergen elimination or
      anti-inflammatory therapy appears to be more effective than acid suppression in
      these patients. This review focuses on clinicopathological features and diagnosis
      of EOE in adults and children.

PMID- 18038309
TI  - Small and microscopically detected gastrointestinal stromal tumours: an overview.
AB  - Small or microscopic gastrointestinal stromal tumours (GISTs) have been the focus
      of recent publications. These lesions may accompany clinically overt GISTs or be
      found incidentally in resection specimens for gastro-oesophageal malignancies.
      While the majority of cases consist of single lesions, approximately 30% may be
      multiple (usually two or three such lesions). Several appellations have been
      employed to describe these small GISTs: minute GISTs, GIST tumourlets,
      interstitial cell of Cajal (ICC) hyperplasia, microscopic GISTs, minimal GISTs,
      and sclerosing stromal tumourlets. As such, there has been no uniformity in terms
      of the size of these small or microscopic lesions with tumours as small as 0.2 mm
      and those up to 10 mm, all falling within the remit of microscopic or minute
      GISTs. These lesions have a predilection for the gastro-oesophageal junction and
      occur slightly more frequently in the proximal stomach. They are typified by
      spindle-shaped cells set within a hyalinised stroma which also shows
      calcification. Even the smallest lesion has been shown to harbour mutations of
      the c-kit gene. They are biologically indolent, and the majority of lesions
      appear to remain small and/or show evidence of involution. However, it is
      possible that some are the precursors of clinically significant GISTs.

PMID- 18038310
TI  - Differential expression and localisation of gasdermin-like (GSDML), a novel
      member of the cancer-associated GSDMDC protein family, in neoplastic and non
      neoplastic gastric, hepatic, and colon tissues.
AB  - AIM: Gasdermin-like (GSDML) is a novel member of the cancer associated gasdermin
      domain containing (GSDMDC) protein family. The GSDMDC family has been linked to
      cancer development and progression, and this is the first study analysing the
      expression and intracellular localisation of GSDML. METHODS: GSDML gene
      transcription was analysed using quantitative real-time RT-PCR. Anti-peptide
      antibodies against GSDML were developed in rabbits, and an in vitro transcription
      translation reaction was used to verify specificity. The Protein-G affinity
      purified antibodies were used in immunohistochemistry and immunoblotting on
      hepatocellular, gastric, and colorectal carcinomas and non-lesional tissues.
      RESULTS: The GSDML gene was transcribed in human gastric, liver and colon cell
      lines, carcinomas and non-lesional tissues. The GSDML protein was localised to
      the cytoplasm of cells in both tumour and non-lesional tissues. The GSDML protein
      splicing variants range in molecular weight from 35 to 50 kDa, and the expression
      profile varies between tumour and non-tumour. A distinctive vesicular staining
      pattern was exhibited by GSDML in the apical region of gastric chief cells and
      colonic surface mucous cells, and the basal region of neuroendocrine cells.
      CONCLUSION: GSDML may be a secretory or metabolic product involved in a secretory
      pathway, and changes in the regulation of GSDML splicing variant transcription
      and translation may be seen in the development and/or progression of
      gastrointestinal and hepatic cancers.

PMID- 18038311
TI  - Real-time PCR quantification of human telomerase reverse transcriptase (hTERT) in
      colorectal cancer.
AB  - AIMS: Human telomerase reverse transcriptase (hTERT) is believed to a reliable
      marker for telomerase activity. The expression of telomerase activity has not
      been investigated in a consecutive series of patients with colorectal
      adenocarcinoma in North Queensland. The objective of this study was to evaluate
      the significance of hTERT mRNA expression in colorectal adenocarcinoma in North
      Queensland. METHODS: Matched samples of tumour and adjacent non-tumorous mucosa
      samples from 53 colorectal carcinomas and nine colorectal adenomas were
      collected. In all these samples, RNA was extracted and then transcribed to cDNA.
      Real-time polymerase chain reaction (RT-PCR) was used to quantitate expression
      the level of hTERT mRNA. The findings were correlated with the
      clinicopathological features of patients with these tumours prospectively
      collected into a computerised database. RESULTS: hTERT mRNA was expressed in all
      tumour samples. The level of expression in the colorectal adenocarcinomas was
      significantly higher than the corresponding non-tumorous mucosa (p = 0.009, t
      test). The level of expression in the adenocarcinomas was slightly higher than
      those of adenomas, but the difference was not statistically significant. A higher
      level of hTERT expression was often noted in the adenocarcinomas arising from the
      left colon and rectum when compared with those from the right colon (p = 0.029).
      CONCLUSIONS: Colorectal adenocarcinoma revealed expression of telomerase hTERT
      mRNA, which was detected quantitatively by real-time PCR. hTERT could be a
      potential biomarker for colorectal cancer. The difference between proximal and
      distal colorectum in hTERT expression could account for their known different
      clinical behaviour.

PMID- 18038312
TI  - Mutational analysis of FLASH and PTPN13 genes in colorectal carcinomas.
AB  - AIMS: The Fas-Fas ligand system is considered a major pathway for induction of
      apoptosis in cells and tissues. FLASH was identified as a pro-apoptotic protein
      that transmits apoptosis signal during Fas-mediated apoptosis. PTPN13 interacts
      with Fas and functions as both suppressor and inducer of Fas-mediated apoptosis.
      There are polyadenine tracts in both FLASH (A8 and A9 in exon 8) and PTPN13 (A8
      in exon 7) genes that could be frameshift mutation targets in colorectal
      carcinomas. Because genes encoding proteins in Fas-mediated apoptosis frequently
      harbor somatic mutations in cancers, we explored the possibility as to whether
      mutations of FLASH and PTPN13 are a feature of colorectal carcinomas. METHODS: We
      analysed human FLASH in exon 8 and PTPN13 in exon 7 for the detection of somatic
      mutations in 103 colorectal carcinomas by a polymerase chain reaction (PCR)-
      based single-strand conformation polymorphism (SSCP). RESULTS: We detected two
      mutations in FLASH gene, but none in PTPN13 gene. However, the two mutations were
      not frameshift (deletion or insertion) mutations in the polyadenine tracts of
      FLASH. The two mutations consisted of a deletion mutation (c.3734-3737delAGAA)
      and a missense mutation (c.3703A>C). CONCLUSION: These data indicate that
      frameshift mutation in the polyadenine tracts in both FLASH and PTPN13 genes is
      rare in colorectal carcinomas. Also, the data suggest that both FLASH and PTPN13
      mutations in the polyadenine tracts may not have a crucial role in the
      pathogenesis of colorectal carcinomas.

PMID- 18038314
TI  - Role of fragile histidine triad protein expression in pathogenesis of malignant
      pleural mesothelioma.
AB  - AIM: To investigate the relationship of fragile histidine triad (FHIT) and Ki-67
      expression with clinicopathological variables of patients with malignant pleural
      mesothelioma (MPM). METHODS: Formalin-fixed, paraffin-embedded tissue sections of
      30 asbestos induced MPM (epithelial and biphasic) patients were examined for FHIT
      and Ki-67 expression using immunohistochemical techniques and results were
      compared with clinicopathological variables. RESULTS: Immunohistochemical study
      results were as follows: 12 (40%) cases showed low FHIT expression and 18 (60%)
      showed high expression. There was no significant relationship between FHIT and
      age, gender or histological subtypes (p > 0.05). Ki-67 expression was 'low' in 13
      (43.3%) cases and 'high' in 17 (56.7%) cases. No correlation could be
      demonstrated between Ki-67 expression and age, gender or histological subtypes (p
      > 0.05). No significant association was observed between FHIT and Ki-67
      expression in MPM. CONCLUSION: The results support the role of FHIT as a tumour
      suppressor gene in asbestos induced MPM. There is no significant correlation
      between FHIT and cell proliferation marker expressions in malignant pleural
      mesothelioma. Therefore, it can be concluded that loss of FHIT does not interfere
      with tumour proliferation. This can be accepted as evidence for an early role of
      FHIT loss in carcinogenesis; however, it needs to be strengthened by further
      studies.

PMID- 18038313
TI  - Does HepPar-1 immunoexpression have a role in differential diagnosis of
      periampullary cancer?
AB  - AIMS: Histological subtyping of periampullary carcinomas is considered as a
      criterion for prognosis and therapeutic implications of these tumours. We
      assessed the immunoexpression rates of HepPar-1, CDX2 and MUC2 antibodies in
      different subtypes of periampullary adenocarcinomas (PAC), intestinal and
      pancreatobiliary, in order to assess their impact on differential diagnosis of
      this group of cancers. The expression of antibodies was also measured in ductal
      adenocarcinoma of the pancreatic head (DAPH). METHODS: Sixty-five patients with
      PAC and DAPH who underwent pancreatic Whipple resection constituted the study
      cohort. Of these, 46 (71%) had PAC, and 19 (29%) had DAPH. Among PACs, 20 (44%)
      were intestinal and 26 (56%) were pancreatobiliary type. RESULTS: HepPar-1
      immunoreactivity was detected in 18 (39%) of all PACs. The rate of HepPar-1
      expression was significantly higher in intestinal type PAC (75%) than it was in
      pancreatobiliary type (12%). The sensitivity, specificity, and accuracy of HepPar
      1 immunoexpression for diagnosing intestinal type PAC were 75% , 89%, and 83%,
      respectively. Similarly, the rates of both CDX2 and MUC2 expressions were
      significantly higher in intestinal type PAC (80%) than they were in
      pancreatobiliary type (8%). The sensitivity, specificity, and accuracy of both
      CDX2 and MUC2 immunoexpressions for intestinal type PAC were 80%, 92%, and 87%,
      respectively. CONCLUSION: HepPar-1 antibody was found to be a highly sensitive
      and specific marker for distinguishing intestinal type from pancreatobiliary type
      among PACs. In addition to CDX2 and MUC2 antibodies, HepPar-1 immunoexpression
      seems to have a potential role in differential diagnosis of PACs.

PMID- 18038315
TI  - Hypothermia fatalities in a temperate climate: Sydney, Australia.
AB  - AIMS: Fatal hypothermia is well known to occur in cold climates, with previous
      case series reflecting this. However, hypothermia can also occur in temperate
      climates. This case series describes the features and circumstances surrounding
      hypothermia-related deaths in Sydney, Australia. METHODS: The files of
      hypothermia-related deaths were reviewed at the Department of Forensic Medicine,
      Glebe between 1 January 2001 and 31 December 2005 via a search of electronic
      autopsy records. RESULTS: Twenty-four cases of fatal hypothermia were found. Many
      of the deaths occurred in winter (46%). The mean age was 76 years (range 56-92),
      with a female predominance (63%). Risk factors for hypothermia were identified in
      58%. The mean body mass index (BMI) was 22 (range 15-33). Nineteen cases (79%)
      were found indoors. Four decedents were found naked, four were dressed in minimal
      amounts of clothing, and paradoxical undressing was found in seven cases.
      Pathological findings included gastric erosions (79%), and patchy reddish brown
      discoloration over large joints (75%). The majority of cases had significant pre
      existing natural disease processes. Out of 18 cases where toxicology was
      performed, alcohol was detected in four cases, while other psychotropic agents
      were present in four deaths. No illicit drugs were detected. CONCLUSION: This
      study shows that fatal hypothermia, a significant public health problem, is not
      limited to cold climates. Forensic pathologists in Australia need to be aware of
      this condition, and not dismiss death as due to natural disease processes.

PMID- 18038316
TI  - Differentiation of human mesenchymal stem cells into mesangial cells in post
      glomerular injury murine model.
AB  - AIMS: Adult human bone marrow contains a population of mesenchymal stem cells
      (MSC) that contributes to the regeneration of tissues such as bone, cartilage,
      muscle, tendon, and fat. In recent years, it has been shown that functional stem
      cells exist in the adult bone marrow, and they can contribute to renal
      remodelling or reconstitution of injured renal glomeruli, especially mesangial
      cells. The purpose of this study is to examine the ability of MSC isolated from
      human bone marrow to differentiate into mesangial cells in glomerular injured
      athymic mice. METHODS: MSC were isolated from human bone marrow mononuclear cells
      based on plastic adherent properties and expanded in vitro in the culture medium.
      Human mesenchymal stem cells (hMSC) were characterised using microscopy,
      immunophenotyping, and their ability to differentiate into adipocytes,
      chondrocytes, and osteocytes. hMSC were then injected into athymic mice, which
      had induced glomerulonephropathy (GN). RESULTS: Test mice (induced GN and infused
      hMSC) were shown to have anti-human CD105(+) cells present in the kidneys and
      were also positive to anti-human desmin, a marker for mesangial cells.
      Furthermore, immunofluorescence assays also demonstrated that anti-human
      desmin(+) cells in the glomeruli of these test mice were in the proliferation
      stage, being positive to anti-human Ki-67. CONCLUSIONS: These findings indicate
      that hMSC found in renal glomeruli differentiated into mesangial cells in vivo
      after glomerular injury occurred.

PMID- 18038317
TI  - Consensus guidelines on anti-beta 2 glycoprotein I testing and reporting.
AB  - Consensus guidelines on anti-beta 2 glycoprotein I (anti-beta2GPI) testing have
      been developed to help minimise laboratory variation in the performance and
      reporting of assays for these antibodies. These guidelines include minimum and
      optional recommendations for the following aspects of anti-beta2GPI testing and
      reporting: (1) isotype of anti-beta2GPI tested; (2) specimen type; (3) controls
      and assay precision; (4) calibrators; (5) patient samples; (6) rheumatoid factors
      and IgM anti-beta2GPI testing; (7) reporting of results; (8) cutoff values; and
      (9) interpretative comments. Issues related to inter-kit/assay standardisation
      and the manufacturing process of commercial anti-beta2GPI kits/assays have not
      been addressed in the current guidelines.

PMID- 18038318
TI  - Clinical features, epidemiology, antimicrobial resistance, and exotoxin genes
      (including that of Panton-Valentine leukocidin) of gentamicin-susceptible
      methicillin-resistant Staphylococcus aureus (GS-MRSA) isolated at a paediatric
      teaching hospital in New South Wales, Australia.
AB  - AIMS: To describe the epidemiological, clinical, and laboratory features of
      gentamicin-susceptible methicillin-resistant Staphylococcus aureus (GS-MRSA) seen
      at a paediatric teaching hospital. METHODS: Patients from whom GS-MRSA was
      isolated between 1 January 2001 and 31 December 2002 were enrolled. Retrospective
      chart review was performed. Susceptibility testing was performed with the Vitek2
      system; PCR confirmed methicillin resistance. Phage typing and pulsed field gel
      electrophoresis (PFGE) was performed (utilising MLST/SCCmec-defined control
      strains). PCR detection of tst, luk-PV, and entA-entE was performed. RESULTS:
      Eighty-five per cent of all Staphylococcus aureus isolates during the study
      period were methicillin-sensitive, and 15% were MRSA (9% GS-MRSA, 6% gentamicin
      resistant-MRSA). 100 GS-MRSA infections in 98 children were identified: 59 cases
      of skin/soft tissue, four bone and joint, four surgical site infections, three
      pneumonia, eight other types, and 22 represented colonisation. Ninety-nine
      isolates were non-multidrug resistant, but 17 strains were resistant to
      erythromycin, 7 to tetracyclines, 12 to ciprofloxacin, 11 to fusidic acid, 1 each
      to rifampicin and mupirocin. 44 isolates were Oceania strain (ST30-MRSA-IV), 20
      were Queensland strain (ST93-MRSA-IV), ten were UK EMRSA-15 (ST22-MRSA-IV), eight
      were WA MRSA-1 (ST1-MRSA-IV), two were WA MRSA-5 (ST8-MRSA-IV), one was WA MRSA-2
      (ST78slv-MRSA-IV), one was WA MRSA-15 (ST59-MRSA-IV), and the remainder were
      sporadics. Twenty patients were Pacific Islanders, of whom 12 had the Oceania
      strain; ten were Aboriginal, of whom eight had the Queensland strain. Sixty-eight
      isolates possessed luk-PV, including all Queensland strains and 91% of Oceania
      strains. Enterotoxin genes were detected in 25% of the isolates, and tst was
      detected in four isolates. CONCLUSIONS: GS-MRSA is a significant paediatric
      problem in New South Wales: two minority groups are over-represented, multiple
      epidemic strains were detected, most community strains possess luk-PV, and many
      isolates are multidrug resistant.

PMID- 18038319
TI  - Latent human polyomavirus infection in pregnancy: investigation of possible
      transplacental transmission.
AB  - AIMS: The purpose of the study was to investigate the transplacental transmission
      of the human polyomaviruses JCV and BKV. METHODS: Urine and blood samples from
      300 pregnant women underwent cytological analysis to search for 'decoy cells',
      nested PCR to identify presence and genotype of isolated polyomaviruses, and
      sequence analysis of the transcription control region. Nested PCR was also used
      to study the umbilical cord blood of all their newborns. RESULTS: Decoy cells
      were identified in only one urine sample (1/300; 0.33%); polyomavirus DNA was
      detected in 80 urine samples (26.6%) corresponding to BKV alone in 28 samples
      (9.3%), JCV alone in 49 samples (16.3%) and both JCV-BKV in three samples (1%).
      Blood samples were positive in 17 cases (5.6%), corresponding to BKV alone in 10
      (3.3%), and JCV alone in 7 (2.3%). Rearrangements of the transcription control
      region were found in only one urinary JCV strain, consisting of the insertion of
      13 bp at D block, whereas point mutations were identified in 11 BKV and 11 JCV
      strains detected from urine. Sequence analysis of the BKV strains detected in
      blood samples revealed a 20 bp insertion of P block (P42-61) in human chromosomes
      20 (five cases) and 14 (three cases); two JCV strains had single bp point
      mutations. The search for polyomavirus DNA in umbilical cord blood samples was
      always negative. CONCLUSIONS: Polyomavirus DNA was frequently detected in
      pregnancy, whereas genomic rearrangements were rare, and no evidence of
      transplacental transmission of polyomavirus was obtained.

PMID- 18038320
TI  - An unusual cause of refractory seizure. Part 1. Part II.

PMID- 18038321
TI  - First molecular confirmation of an Australian case of type III hereditary
      angioedema.

PMID- 18038322
TI  - Metastatic renal cell carcinoma masquerading as a primary gastric carcinoma
      associated with synchronous early gastric carcinoma.

PMID- 18038323
TI  - Pulmonary intimal sarcoma presenting as an ascending colonic polyp and mimicking
      a gastrointestinal stromal tumour.

PMID- 18038324
TI  - Metastasising pleomorphic adenoma of the parotid presenting as a solitary kidney
      mass.

PMID- 18038325
TI  - Solitary fibrous tumour of the parotid gland.

PMID- 18038326
TI  - Ovarian mucinous tumour with multifocal endocrine cell micronests.

PMID- 18038327
TI  - PEComa of the retroperitoneum.

PMID- 18038328
TI  - Absence of GNAS and EGFL6 mutations in common human cancers.

PMID- 18038329
TI  - Sclerosing lobular hyperplasia: an unusual cause of a benign breast mass in young
      women.

PMID- 18038330
TI  - Epithelioid, cytokeratin expressing malignant solitary fibrous tumour of the
      pleura.

PMID- 18038331
TI  - Kodamaea (Pichia) ohmeri fungaemia complicating acute myeloid leukaemia in a
      patient with haemochromatosis.

PMID- 18038332
TI  - Coronary heart disease in diabetics: prognostic implications and results of
      interventions.
AB  - OBJECTIVES: The aim of the present study was to compare the extent of coronary
      disease and subsequent survival in diabetics and non-diabetics. DESIGN: From the
      database at Feiring Heart Clinic 13511 patients were identified with no previous
      revascularization and were examined with coronary angiography in the period from
      March 1999 to December 31, 2005. In the cohort 1,475 patients were diabetics.
      Their survival status of May 31, 2006 was ascertained through the Norwegian
      National Registry. RESULTS: Diabetics were more symptomatic and had a more severe
      coronary artery disease at the time of referral with more than 40% having three
      vessel disease. The unadjusted survival was lower in the diabetics. After
      adjustment through Cox regression, diabetes mellitus remained a risk factor for
      subsequent death (overall hazard ratio 1.33), with the excess mortality mainly
      residing in smoking diabetics. CONCLUSIONS: Diabetics were more severely diseased
      at the time of referral. In Cox regression diabetes mellitus remained a
      significant risk factor for death in smokers except in the cohort treated with
      CABG.

PMID- 18038336
TI  - Precursors to a theory of mind in infancy: perspectives for research on autism.
AB  - There is ample evidence for a conceptual deficit in normally developing 3-year
      olds' and autistic children's understanding of the mind. Recent research using
      nonverbal tasks has challenged this view since even 15-month-old infants appear
      to base their action predictions on a representation of the agent's beliefs
      (Onishi & Baillargeon, 2005). Our own findings from looking-time experiments
      indicate, however, that 16-month-olds' action predictions depend on behavioural
      and situational cues, rather than on a person's access to information. Further
      research is reviewed that indicates that 14-month-olds understand what another
      person can and cannot see, and that 18-month-olds predict a person's action from
      what she previously saw, when supported by behavioural cues. These findings
      support a constructivist view of a gradual understanding of conditions for
      knowing during the second year. The relevance of such findings for research on
      autism is discussed.

PMID- 18038335
TI  - Forty years on: Uta Frith's contribution to research on autism and dyslexia, 1966
      2006.
AB  - Uta Frith has made a major contribution to our understanding of developmental
      disorders, especially autism and dyslexia. She has studied the cognitive and
      neurobiological bases of both disorders and demonstrated distinctive impairments
      in social cognition and central coherence in autism, and in phonological
      processing in dyslexia. In this enterprise she has encouraged psychologists to
      work in a theoretical framework that distinguishes between observed behaviour and
      the underlying cognitive and neurobiological processes that mediate that
      behaviour.

PMID- 18038337
TI  - Development of the social brain during adolescence.
AB  - Adolescence is usually defined as the period of psychological and social
      transition between childhood and adulthood. The beginning of adolescence, around
      the onset of puberty, is characterized by large hormonal and physical changes.
      The transition from childhood to adulthood is also characterized by psychological
      changes in terms of identity, self-consciousness, and cognitive flexibility. In
      the past decade, it has been demonstrated that various regions of the human brain
      undergo development during adolescence and beyond. Some of the brain regions that
      undergo particularly protracted development are involved in social cognitive
      function in adults. In the first section of this paper, I briefly describe
      evidence for a circumscribed network of brain regions involved in understanding
      other people. Next, I describe evidence that some of these brain regions undergo
      structural development during adolescence. Finally, I discuss recent studies that
      have investigated social cognitive development during adolescence.

PMID- 18038338
TI  - The power of the positive: revisiting weak coherence in autism spectrum
      disorders.
AB  - This paper reexamines Frith's original concept of weak coherence, its historical
      origins, recent reformulations, and alternative accounts. We suggest that the key
      notion of reduced global integration of information, which Frith proposed to
      underlie the assets in local processing, has been neglected in recent accounts of
      autism spectrum disorders (ASD). In fact, most paradigms used to test weak
      coherence conflate global and local processing, often placing them in direct
      trade-off, so that it is not possible to tell whether patterns of performance in
      ASD reflect reduced global processing, increased local processing, or both. We
      review the literature from typical development and ASD that may be pertinent to
      this distinction and examine some data from our own studies. Only once tasks are
      devised that measure separately the effects of reduced global processing and
      increased local processing will it be possible to test the on-line and
      developmental relations between these two aspects of "weak coherence". Some
      preliminary ideas about these relationships are discussed, and suggestions are
      made for why disentangling two possibly independent dimensions of weak coherence
      may be timely and productive.

PMID- 18038339
TI  - Autism, hypersystemizing, and truth.
AB  - Evidence is reviewed suggesting that, in the general population, empathizing and
      systemizing show strong sex differences. The function of systemizing is to
      predict lawful events, including lawful change, or patterns in data. Also
      reviewed is the evidence that individuals on the autistic spectrum have degrees
      of empathizing difficulties alongside hypersystemizing. The hypersystemizing
      theory of autism spectrum conditions (ASC) proposes that people with ASC have an
      unusually strong drive to systemize. This can explain their preference for
      systems that change in highly lawful or predictable ways; why they become
      disabled when faced with systems characterized by less lawful change; and their
      "need for sameness" or "resistance to change". If "truth" is defined as lawful
      patterns in data then, according to the hypersystemizing theory, people with ASC
      are strongly driven to discover the "truth".

PMID- 18038340
TI  - The curious incident of the photo that was accused of being false: issues of
      domain specificity in development, autism, and brain imaging.
AB  - We resume an exchange of ideas with Uta Frith that started before the turn of the
      century. The curious incident responsible for this exchange was the finding that
      children with autism fail tests of false belief, while they pass Zaitchik's
      (1990) photograph task (Leekam & Perner, 1991). This finding led to the
      conclusion that children with autism have a domain-specific impairment in Theory
      of Mind (mental representations), because the photograph task and the false
      belief task are structurally equivalent except for the nonmental character of
      photographs. In this paper we argue that the false-belief task and the false
      photograph task are not structurally equivalent and are not empirically
      associated. Instead a truly structurally equivalent task is the false-sign task.
      Performance on this task is strongly associated with the false-belief task. A
      version of this task, the misleading-signal task, also poses severe problems for
      children with autism (Bowler, Briskman, Gurvidi, & Fornells-Ambrojo, 2005). These
      new findings therefore challenge the earlier interpretation of a domain-specific
      difficulty in inferring mental states and suggest that children with autism also
      have difficulty understanding misleading nonmental objects. Brain imaging data
      using false-belief, "false"-photo, and false-sign scenarios provide further
      supporting evidence for our conclusions.

PMID- 18038341
TI  - Frames of reference in social cognition.
AB  - How is mindreading affected by social context? It is often implicitly assumed
      that there is one single way to understand others, whatever the situation or the
      identity of the person. In contrast, I emphasize the duality of functions of
      mindreading depending on the context (social interaction and social observation),
      as well as the duality of social frames of reference (egocentric and
      allocentric). I argue in favour of a functional distinction between knowledge
      oriented mindreading and interaction-oriented mindreading. They both aim at
      understanding other people's behaviour. But they do so using different
      strategies. However, to say that mindreading has two functions does not suffice
      to show that there are two kinds of mindreading. One and the same ability could
      accomplish different functions. Unfortunately, there has been almost no
      experimental data on a possible dissociation between two kinds of mindreading
      abilities. Nonetheless, I discuss a few results that point towards a dual
      ability.

PMID- 18038342
TI  - Emulation and mimicry for social interaction: a theoretical approach to imitation
      in autism.
AB  - The "broken-mirror" theory of autism argues that dysfunction of the "mirror
      neuron system" is a root cause of social disability in autism. The present paper
      aims to scrutinize this theory and, when it breaks down, to provide an
      alternative. Current evidence suggests that children with autism are able to
      understand and emulate goal-directed actions, but may have specific impairments
      in automatic mimicry of actions without goals. These data are not compatible with
      the broken-mirror theory, but can be accounted for by a new model called EP-M.
      The EP-M model segments the mirror neuron system into an indirect, parietal route
      for goal emulation and planning (EP) and a direct occipital-frontal route for
      mimicry (M). This fractionation is consistent with neuroimaging and behavioural
      studies of the mirror neuron system in typical children and adults. I suggest
      that top-down modulation of the direct M route may be dysfunctional in
      individuals with autism, leading to abnormal behaviours on mimicry tasks as well
      as other social disabilities.

PMID- 18038343
TI  - What can autism and dyslexia tell us about intelligence?
AB  - This paper argues that understanding developmental disorders requires developing
      theories and models that explicitly represent the role of general intelligence in
      the cognitive phenotype of the disorder. In the case of autism it is argued that
      the low-IQ scores of people with autism are not likely to be due to a deficit in
      the cognitive process that is arguably the major cause of mental retardation -
      namely, speed of processing - but rather low IQ reflects the pervasive and
      cascading effects of the deficit in the information-processing module that causes
      autism. In the case of dyslexia, two radically different models of reading
      disorder (ability = disability and a modular deficit model) are likely to be
      influenced by the effect of general intelligence on reading performance in ways
      that will remain unclear without an explicit model of how general intelligence
      influences reading.

PMID- 18038344
TI  - What phonological deficit?
AB  - We review a series of experiments aimed at understanding the nature of the
      phonological deficit in developmental dyslexia. These experiments investigate
      input and output phonological representations, phonological grammar, foreign
      speech perception and production, and unconscious speech processing and lexical
      access. Our results converge on the observation that the phonological
      representations of people with dyslexia may be intact, and that the phonological
      deficit surfaces only as a function of certain task requirements, notably short
      term memory, conscious awareness, and time constraints. In an attempt to
      reformulate those task requirements more economically, we propose that
      individuals with dyslexia have a deficit in access to phonological
      representations. We discuss the explanatory power of this concept and we
      speculate that a similar notion might also adequately describe the nature of
      other associated cognitive deficits when present.

PMID- 18038345
TI  - Specific disorders and broader phenotypes: the case of dyslexia.
AB  - Two studies investigating the cognitive phenotype of dyslexia are described.
      Study 1 compared three groups of English and Italian children on speed of
      processing tasks: (a) children with dyslexia, (b) generally delayed poor readers
      and (c) CA-controls. In tests of simple and choice reaction time and two visual
      scanning tasks, children with dyslexia performed like controls and significantly
      faster than generally delayed poor readers. A second prospective longitudinal
      investigation of children at family risk of dyslexia showed that problems of
      literacy development were less circumscribed, with affected children showing
      phonological deficits in the context of more general oral language difficulties.
      An important finding was that the risk of dyslexia was continuous in this sample;
      among at-risk children with normal literacy development, mild impairments of
      phonological skills were apparent early in development, and subtle difficulties
      with reading fluency and spelling emerged in early adolescence. A case series
      extended these findings to show that phonological deficits alone are insufficient
      to explain literacy difficulties, and it is children with multiple deficits
      (including language problems) that are more likely to succumb to reading failure.

PMID- 18038346
TI  - Fine cuts of empathy and the amygdala: dissociable deficits in psychopathy and
      autism.
AB  - In the current paper, the "fine cuts" approach advocated by Uta Frith is applied
      to our understanding of empathy and amygdala dysfunction in two disorders,
      psychopathy and autism. A fine cut is made between cognitive (i.e., Theory of
      Mind) and emotional empathy. The literature with respect to psychopathy and
      autism and these two functions is then considered. A fine cut is also made
      between the amygdala's role in stimulus-reinforcement association and specific
      aspects of social cognition. Again the literature with respect to psychopathy and
      autism and these two functions of the amygdala is considered. It is concluded
      that while both conditions can be considered disorders of social cognition, fine
      cuts can be made dissociating the impairments associated with each.

PMID- 18038347
TI  - Cognition to genes via the brain in the study of conduct disorder.
AB  - Although a single diagnostic label, conduct disorder, is currently applied to
      children exhibiting antisocial behaviour, multiple routes to the same behavioural
      phenomena exist. Morton and Frith's (1995) causal modelling has been
      fundamentally important in influencing models of cognitive/affective and
      associated neural differences between callous-unemotional (CU) and
      reactive/threat-based antisocial behaviour. Current behavioural genetic research
      is still catching up with the developmental cognitive neuroscience, and very few
      genetically informative studies differentiate between these two subtypes of
      antisocial behaviour. Our own work with preadolescent twins suggests that while
      the CU subtype is genetically vulnerable to antisocial behaviour, the non-CU
      subtype manifests a primarily environmental aetiology to their antisocial
      behaviour. Molecular genetic work to date has not differentiated between these
      two subtypes, and we highlight why it might be of interest to do so. Finally, we
      discuss how the novel approach of imaging genetics could be harnessed to study
      genes to cognition pathways for different subtypes of conduct disorder. Uta
      Frith's contributions to articulating research strategies for developmental
      disorders are important in conducting and interpreting this work.

PMID- 18038349
TI  - Imaging findings of primary well-differentiated liposarcoma of the liver: a case
      report.
AB  - Primary liposarcoma of the liver is extremely rare. We report here on a case of
      primary well-differentiated liposarcoma in the left hepatic lobe of a 63-year-old
      woman. Abdominal ultrasonography showed a well-defined, echogenic, round mass.
      Abdominal computed tomography (CT) and magnetic resonance (MR) images showed an
      almost fatty, lobulated mass with a few, random distributed vascular structures
      and a small area of nodular enhancement. The resected tumor appeared as a well
      defined, round, tan-yellow mass. Histological analysis showed a well
      differentiated liposarcoma.

PMID- 18038351
TI  - Successful occlusion of spontaneous portosystemic shunts leading to
      encephalopathy in a non-cirrhotic patient by using the Amplatzer vascular plug.
AB  - A 55-year-old woman presented with recurrent, recently aggravated encephalopathic
      episodes. However, the patient had no evidence of liver cirrhosis, and her serum
      ammonia level was high. An abdominal computed tomography (CT) scan revealed two
      portal-systemic venous shunts and, accordingly, she was diagnosed as having non
      cirrhotic portal-systemic encephalopathy due to portal-systemic shunts. The
      shunts were successfully occluded using Amplatzer vascular plugs, and this led to
      a normalization of her blood ammonia levels immediately after occlusion. Over a 3
      month follow-up, the patient experienced no complications or symptoms, and no
      shunt recanalization was detected by CT. The described case demonstrates that the
      Amplatzer vascular plug offers a useful option for occluding portal-systemic
      shunts responsible for encephalopathy.

PMID- 18038353
TI  - Accuracy and precision in the detection of articular cartilage lesions using
      magnetic resonance imaging at 1.5 Tesla in an in vitro study with orthopedic and
      histopathologic correlation.
AB  - BACKGROUND: Magnetic resonance (MR) sequences for cartilage visualization have
      been the target of numerous studies, and the optimal sequence for cartilage
      imaging remains a matter of debate in the literature. PURPOSE: To compare MR
      findings with different MR sequences for the detection of cartilage lesions in
      fresh deep-frozen human cadaveric patellae in an in vitro setting. MATERIAL AND
      METHODS: Ten cadaveric patellae were imaged on a 1.5T MR scanner with a 2x2
      channel carotid sandwich coil and a conventional knee coil, and compared with
      orthopedic findings and gold-standard histopathology. MR sequences were: a) fat
      saturated (FS) proton density-weighted (PDw) turbo spin-echo (TSE) sequence
      (TR/TE 4000/39 ms); b) T2-weighted (T2w) double-echo steady-state (DESS) 3D water
      excitation (we) sequence (TR/TE 17/4.7 ms); c) 3D-PDw-SPACE (sampling perfection
      with application-optimized contrasts using different flip-angle evolutions)-we
      sequence (TR/TE 1800/19 ms). Accuracy, Kendall's tau-b correlation, and weighted
      kappa coefficients were calculated. RESULTS: Accuracy for cartilage lesion
      detection with the FS PDw-TSE sequence and the carotid coil was 78.3%, and with
      the knee coil 73.9%. For the T2wDESS-3D-we sequence, the corresponding values
      were 69.5% and 65.2%, and for the 3D-PDw-SPACE-we sequence 65.2% and 60.8%,
      respectively. Kendall's tau-b correlation ranged between 0.508 for the 3D-PDw
      SPACE-we sequence (knee coil) and 0.720 for the FS PDw-TSE sequence (carotid and
      knee coil). Weighted kappa coefficient was lowest for the 3D-PDw-SPACE-we
      sequence (knee coil) at 0.607, and highest for the carotid coil and FS PDw-TSE
      sequence at 0.779. CONCLUSION: The evaluated FS PDw-TSE sequences are superior in
      comparison to the T2wDESS-3D-we and 3D-PDw-SPACE-we sequences in the in vitro
      setting for the detection of cartilage lesions, and are comparable to results
      reported in the literature.

PMID- 18038355
TI  - Executive functioning in older adults with mild cognitive impairment: MCI has
      effects on planning, but not on inhibition.
AB  - In this study, we compared executive functioning in 32 mild cognitive impairment
      (MCI) individuals with that of normally aging controls. Cognitive planning tests
      (Trail Making, Porteus Maze Test, verbal fluency tests) show a group difference
      favoring the normal controls, but tests for inhibition of prepotent responses (no
      go accuracy, two measures of the Stroop effect, and negative priming) failed to
      uncover a significant group difference. The results indicate that there is no
      general executive control function impairment in MCI; rather, the deficits found
      are compatible with the hypothesis that MCI is an accelerated form of normal
      aging.

PMID- 18038356
TI  - Influence of age and sex on line bisection: a study of normal performance with
      implications for visuospatial neglect.
AB  - Line bisection is an established clinical task used to diagnose visuospatial
      neglect. To date, few studies have considered the extent to which age and sex as
      background variables contribute to bisection performance. Both variables affect
      the neural substrates underlying cognitive processes and hence the behavioural
      performance of bisection. The purpose of this study was to examine the effects of
      age and sex on normal bisection performance, using three different line lengths
      to elucidate the influence of these potential contributing factors. Seventy men
      and 70 women, divided equally into seven age-cohorts between 14 and 80 years,
      bisected lines. Results indicated clear age- and sex-related differences both in
      the magnitude and direction of bisection deviations across the three line
      lengths. Differences are discussed in terms of neural changes across the adult
      lifespan including hemispheric differences and hormonally mediated changes.

PMID- 18038357
TI  - Age-group differences in inhibiting an oculomotor response.
AB  - Age-group differences were examined in the delayed oculomotor response task,
      which requires that observers delay the execution of a saccade (eye movement)
      toward an abrupt-onset visual cue. This task differs from antisaccade and
      attentional capture in that inhibition causes saccades to be postponed, not
      redirected. Older adults executed more premature saccades than young adults, but
      there were no age-group differences in latency or accuracy of saccades executed
      at the proper time. The results suggest that older adults are less capable of
      inhibiting a prepotent saccadic response, but that other aspects of visual
      working memory related to the task are preserved.

PMID- 18038358
TI  - Age-related deficits in face recognition are related to underlying changes in
      scanning behavior.
AB  - Previous studies demonstrating age-related impairments in recognition memory for
      faces are suggestive of underlying differences in face processing. To study these
      differences, we monitored eye movements while younger and older adults viewed
      younger and older faces. Compared to the younger group, older adults showed
      increased sampling of facial features, and more transitions. However, their
      scanning behavior was most similar to the younger group when looking at older
      faces. Moreover, while older adults exhibited worse recognition memory than
      younger adults overall, their memory was more accurate for older faces. These
      findings suggest that age-related differences in recognition memory for faces may
      be related to changes in scanning behavior, and that older adults may use social
      group status as a compensatory processing strategy.

PMID- 18038359
TI  - Within-person variability in response speed as an indicator of cognitive
      impairment in older adults.
AB  - Within-person variability may be an important indicator of central nervous system
      compromise. In this study, within-person variability in response speed was
      examined in community-dwelling older adults, ages 64-92 years, using a new
      framework that takes into account both the extent (single versus multiple domains
      affected) and nature (amnestic versus non-amnestic) of the cognitive impairment.
      Those with multiple domains of impairment were more variable than those who
      showed an isolated area of impairment, regardless of whether memory was one of
      the domains affected. Further, for those with difficulties in two or more non
      memory domains, increased variability was most evident in more cognitively
      demanding situations, when individuals had to manipulate information held briefly
      in mind, switch cognitive set or inhibit an automatic response. Finally, group
      differentiation was better achieved when within-person variability as opposed to
      mean speed of performance was considered.

PMID- 18038360
TI  - The roles of working memory updating and processing speed in mediating age
      related differences in fluid intelligence.
AB  - This study was conducted to investigate the relative roles of working memory
      updating (updating) and processing speed in mediating age-related differences in
      fluid intelligence. A sample of 142 normal adults between 18 and 85 years of age
      performed a set of updating, processing speed, and fluid intelligence tasks.
      Hierarchical regression analyses indicated that the proportion of unique age
      related variance in updating measures was related to the complexity of speed
      measures. There was a larger proportion of unique age-related variance in
      updating measures after controlling for the variance in simpler speed measures.
      Moreover, structural equation modeling showed that updating mediated almost all
      the age-related effects on fluid intelligence. These results suggest that
      updating, but not speed, is the critical mediator between age and fluid
      intelligence. In addition, the speed mediation of age-related differences in
      fluid intelligence as indicated by previous studies is at least partially derived
      from the executive component of speed measures.

PMID- 18038361
TI  - Nod-like receptors in innate immunity and inflammatory diseases.
AB  - Over the past few years the field of innate immunity has undergone a revolution
      with the discovery of pattern recognition molecules (PRM) and their role in
      microbe detection. Among these molecules, the Nod-like receptors (NLRs) have
      emerged as key microbial sensors that participate in the global immune responses
      to pathogens and contribute to the resolution of infections. This growing group
      of proteins is divided into subfamilies with basis in their different signaling
      domains. Prominent among them are Nod1, Nod2, Nalp3, Ipaf, and Naip that have
      been shown to play important roles against intracellular bacteria. Furthermore,
      mutations in the genes that encode these proteins have been associated with
      complex inflammatory disorders including Crohn's disease, asthma, familial cold
      urticaria, Muckle-Wells syndrome, and Blau syndrome. In this review we will
      present the current knowledge on the role of these proteins in immunity and
      inflammatory diseases.

PMID- 18038362
TI  - Comment on "Discriminating toxicant classes by mode of action: 3. Substructure
      indicators" (M. Nendza and M. Muller, SAR QSAR Environ. Res. 18 155 (2007)).

PMID- 18038364
TI  - Prediction of biological activity profiles of cyanobacterial secondary
      metabolites.
AB  - Over the past decade cyanobacteria have become an interesting source of new
      classes of pharmacologically active natural products. Some cyanobacterial
      secondary metabolites (CSMs) are also well known for their toxic effects on
      living species. The PASS (Prediction of Activity Spectra for Substances) computer
      program, which is able to simultaneously predict more than one thousand
      biological and toxicological activities from only the structural formulas of the
      chemicals, was used to predict the biological activity profile of 681 CSMs.
      Multivariate methods were employed to structure and analyse this wealth of
      biological and chemical information. PASS predictions were successfully compared
      to the available information on the pharmacological and toxicological activity of
      these compounds.

PMID- 18038365
TI  - Handling uncertainties in toxicity modelling using a fuzzy filter.
AB  - A fundamental concern in the Quantitative Structure-Activity Relationship
      approach to toxicity evaluation is the generalization of the model over a wide
      range of compounds. The data driven modelling of toxicity, due to the complex and
      ill-defined nature of eco-toxicological systems, is an uncertain process. The
      development of a toxicity predicting model without considering uncertainties may
      produce a model with a low generalization performance. This study presents a
      novel approach to toxicity modelling that handles the involved uncertainties
      using a fuzzy filter, and thus improves the generalization capability of the
      model. The method is illustrated by considering a data set dealing with the
      fathead minnow (Pimephales promelas) toxicity of 568 organic compounds.

PMID- 18038366
TI  - Molecular modelling and QSAR analysis of the estrogenic activity of terpenoids
      isolated from Ferula plants.
AB  - The relationship between chemical structure and estrogenic activity in a series
      of terpenoid esters with aromatic and aliphatic acid substituents isolated from
      Ferula plants, was studied. The fragments of the terpenoid structure that are
      potentially responsible for estrogenic activity were revealed. A quantitative
      structure-estrogenic activity study has been carried out using the QSAR approach
      with use of data derived from quantum-chemical calculations as well as data
      generated from three-dimensional structures of terpenoids. A number of molecular
      descriptors was obtained from the density functional theory (DFT) at the B3LYP/6
      31G(d, p) level of calculation. Comparative analysis of the quantum-chemical
      computational data was also performed to confirm hypothesis concerning importance
      of the distance between the oxygen of alcohol hydroxyl group and the functional
      group in the para-position of the benzene ring (the hydroxyl or methoxy group).
      Use of the Genetic Algorithm in the QSAR analysis allowed the structural and
      physicochemical parameters of the terpenoids responsible for estrogenic activity
      to be determined. A significant QSAR model was obtained with an r(2) value of
      0.892. The resulting model showed a reliable dependence of estrogenic activity of
      the terpenoids on such parameters as molecular shape, number of phenolic groups,
      surface polarity and the energy of the highest occupied molecular orbital.

PMID- 18038367
TI  - Toxicity study of allelochemical-like pesticides by a combination of 3D-QSAR,
      docking, Local Binding Energy (LBE) and GRID approaches.
AB  - 3D-QSAR, Docking, Local Binding Energy (LBE) and GRID methods were integrated as
      a tool for predicting toxicity and studying mechanisms of action. The method was
      tested on a set of 73 allelochemical-like pesticides, for which acute toxicity
      (LD(50)) for the rat was available. 3D-QSAR gave a model with high predictive
      ability and the regression maps indicated the important toxic chemical
      substituents. Significant ligand-protein residue interactions and oxidation
      positions in the binding site were found by docking analysis using CYP1A2
      homology modelling. The binding energies of the compounds and the important
      substituents (Local Binding Energy, LBE) were calculated in order to demonstrate
      quantitatively the substituent contributions in the metabolism and toxicity. The
      GRID examination identified the CYP1A2 binding pocket feature. Finally, a 3D-QSAR
      map was compared to the GRID map, showing good overlaps and confirming the
      important role of CYP1A2 in allelochemical-like compounds toxicity.

PMID- 18038368
TI  - Data analysis and alternative modelling of MITI-I aerobic biodegradation.
AB  - An alternate representation of the biodegradation of chemicals (biochemical
      oxygen demand (BOD) amount instead of BOD-based degradation percentage) allows
      the derivation of an improved QSAR model. The structural descriptors for this
      model are related to biodegradation mechanisms. A linear group contribution model
      of 99 variables was derived from a training set of 1190 chemicals. The squared
      correlation coefficients for self-prediction and for 20%-off cross-validation
      were 0.83 and 0.69, respectively. Additional external validation with 62 reported
      in the literature chemicals resulted in 91% overall correct classification,
      although ready biodegradable molecules were too few and predicted poorly (two out
      of five correct).

PMID- 18038369
TI  - Quantitative structure-activity relationships for a series of selective estrogen
      receptor-beta modulators.
AB  - The estrogen receptor-beta subtype (ERbeta) is an attractive drug target for the
      development of novel therapeutic agents for hormone replacement therapy. Hologram
      quantitative structure-activity relationships (HQSAR) were conducted on a series
      of 6-phenylnaphthalene and 2-phenylquinoline derivatives, employing values of
      ERbeta binding affinity. A training set of 65 compounds served to derive the
      models. The best statistical HQSAR model (q(2) = 0.73 and r(2) = 0.91) was
      generated using atoms, bonds, connections and donor and acceptor as fragment
      distinction parameters, and fragment size default (4-7) with hologram length of
      199. The model was used to predict the binding affinity of an external test set
      of 16 compounds, and the predicted values were in good agreement with the
      experimental results. The final HQSAR model and the information obtained from 2D
      contribution maps should be useful for the design of novel ERbeta modulators
      having improved affinity.

PMID- 18038370
TI  - QSAR modelling of water quality indices of alkylphenol pollutants.
AB  - The aim of this study was to determine the degradability of 26 Alkylphenols (APs)
      by Chemical Oxygen Demand (COD) and/or 5-day Biochemical Oxygen Demand (BOD(5)),
      and to describe these data from Quantitative Structure-activity Relationships
      (QSARs). Statistical analysis techniques, such as Multiple Linear Regression
      (MLR), Principal Component Regression (PCR), Partial Least-Squares (PLS)
      Regression and Neural Network (NN) were carried out to calibrate and validate
      four-descriptor QSAR models using two different types of descriptor sets. Stable
      MLR-QSAR models using Leave-One-Out (LOO) were obtained with high predictability
      performance: r(2) = 0.924, Q(2)(cv) =0.854 for log (1/BOD) model on 24 APs and
      r(2) = 0.888, Q(2)(cv) = 0.818 for log (1/COD) on all the studied APs. The MLR
      models, built with four Dragon descriptors selected by Genetic Algorithm (GA),
      presented the following performances on 24 APs: r(2) = 0.889, Q(2)(cv) = 0.848
      for log (1/BOD(5)) and r(2) = 0.885, Q(2)(cv) = 0.834 for log (1/COD) on 26
      compounds. From these results, it is expected that the QSAR models generated
      could be successfully expanded to predict the biological and chemical activities
      of structurally diverse AP compounds.

PMID- 18038371
TI  - Prediction of acute toxicity of organophosphorus pesticides using topological
      indices.
AB  - Topological indices were used in the prediction of the acute toxicity
      (intraperitoneal and oral LD(50)) of organophosphorus pesticides on rats. Models
      with six variables for the prediction of LD(50)-i.p. (r = 0.849, Q(2) = 0.613)
      and eight variables for LD(50)-oral (r = 0.906, Q(2) = 0.701) were selected.
      External group and cross-validation by use of leave-n-out tests were also
      performed in order to assess the stability and the prediction performance of the
      selected topological models.

PMID- 18038373
TI  - [Investigation of neural stem cell-derived donor contribution in the inner ear
      following blastocyst injection].
AB  - BACKGROUND: Utilising the enormous proliferation and multi-lineage
      differentiation potentials of somatic stem cells represents a possible
      therapeutical strategy for diseases of non-regenerative tissues like the inner
      ear. In the current study, the possibility of murine neural stem cells to
      contribute to the developing inner ear following blastocyst injection was
      investigated. METHODS: Fetal brain-derived neural stem cells from the embryonic
      day 14 cortex of male mice were isolated and expanded for four weeks in
      neurobasal media supplemented with bFGF and EGF. Neural stem cells of male
      animals were harvested, injected into blastocysts and the blastocysts were
      transferred into pseudo-pregnant foster animals. Each blastocyst was injected
      with 5-15 microspheres growing from single cell suspension from neurospheres
      dissociated the day before. The resulting mice were investigated six months POST
      PARTUM for the presence of donor cells. Brainstem evoked response audiometry
      (BERA) was performed in six animals. To visualize donor cells Lac-Z staining was
      performed on sliced cochleas of two animals. In addition, the cochleas of four
      female animals were isolated and genomic DNA of the entire cochlea was analyzed
      for donor contribution by Y-chromosome-specific PCR. RESULTS: All animals had
      normal thresholds in brainstem evoked response audiometry. The male-specific PCR
      product indicating the presence of male donor cells were detected in the cochleas
      of three of the four female animals investigated. In two animals, male donor
      cells were detected unilateral, in one animal bilateral. CONCLUSION: The results
      suggest that descendants of neural stem cells are detectable in the inner ear
      after injection into blastocysts and possess the ability to integrate into the
      developing inner ear without obvious loss in hearing function.

PMID- 18038374
TI  - [Low level auditory skills in school children attending third and fourth grade].
AB  - BACKGROUND: In Germany testing auditory low level skills has gained some
      popularity. However only few studies have provided norms. Prior to further
      testing we here aimed at establishing normal values for school children. METHODS:
      DESIGN: prospective study. SAMPLE: School children attending 3rd and 4th grade.
      DEPENDENT VARIABLES: just noticeable differences for intensity and frequency
      (JNDI, JNDF), gap detection (GD) monaural and binaural temporal order judgement
      (TOJB and TOJM). STATISTICS: descriptive and correlational analysis. RESULTS:
      Data did not follow a normal distribution, i. e. only few children had poor
      results whereas the majority of children had fair to excellent results.
      Correlational analysis indicated some dependency among auditory low level skills
      as tested here. DISCUSSION: These data are consistent with previously described
      data that auditory low levels maturate during development at least up to age 10.
      However the significance of poor results for impaired language acquisition
      remains unclear.

PMID- 18038375
TI  - [Small cell carcinoma of parotid gland--a case report].
AB  - BACKGROUND: Small cell carcinoma of the major salivary glands are very seldom. If
      there is such a tumor always have in mind that it can be a metastatic process of
      another small cell carcinoma in other locations of the body. That's why first of
      all a primary in the bronchial system has to be excluded with special
      diagnostics. CASE REPORT: We present the case of a 72-year-old woman suffering
      from a small cell carcinoma of Parotid gland. Because a surgical therapy was
      impossible she underwent a radiotherapy. CONCLUSION: First choice for therapy of
      tumors of the major salivary glands is surgical therapy in combination with
      radiation/chemotherapy. If this is not possible a primary radiotherapy sometimes
      in combination with chemotherapy seems to be another therapeutic option.

PMID- 18038376
TI  - Synthesis and anticonvulsant activity of some N-phenyl-2
      phtalimidoethanesulfonamide derivatives.
AB  - In this study, inspired by the structures of the taltrimide, 2
      phthalimidoethanesulphonamide, and the anilide pharmacophore known to be
      synthetically produced anticonvulsant compounds, fifteen N-phenyl-2
      phtalimidoethanesulfonamide derivatives bearing substituents with diverse
      electronic and hydrophobic features on N-phenyl ring were synthesized. The
      structural confirmation of the title compounds was achieved by interpretation of
      spectral and analytical data. The anticonvulsant activity of the title compounds
      was determined against maximal electroshock seizure in mice at a dose level of
      100 mg/kg. The preliminary screening results indicated that the exchange of the N
      isopropyl moiety for an N-phenyl ring in the taltrimide molecule abolished the
      anticonvulsant activity. However, introducing certain substituents, such as
      nitro, methyl, and chloro, into the N-phenyl ring lead to more active compounds
      in comparison to the unsubstituted derivatives.

PMID- 18038377
TI  - A combination of lacunary polyoxometalates and high-nuclear transition-metal
      clusters under hydrothermal conditions. Part II: From double cluster, dimer, and
      tetramer to three-dimensional frameworks.
AB  - The hydrothermal reactions of trivacant Keggin A-alpha-XW(9)O(34) polyoxoanions
      (X=P(V)/Si(IV)) with transition-metal ions (Ni(II)/Cu(II)/Fe(II)) in the presence
      of amines result in eight novel high-nuclear transition-metal-substituted
      polyoxotungstates [{Ni(7)(mu(3)-OH)(3)O(2)(dap)(3)(H(2)O)(6)}(B-alpha
      PW(9)O(34))][{Ni(6)(mu(3)-OH)(3)(dap)(3)(H(2)O)(6)}(B-alpha
      PW(9)O(34))][Ni(dap)(2)(H(2)O)(2)]4.5 H(2)O (1),
      [Cu(dap)(H(2)O)(3)](2)[{Cu(8)(dap)(4)(H(2)O)(2)}(B-alpha-SiW(9)O(34))(2)]6 H(2)O
      (2), (enH(2))(3)H(15)[{Fe(II) (1.5)Fe(III) (12)(mu(3)-OH)(12)(mu(4)-PO(4))(4)}(B
      alpha-PW(9)O(34))(4)]ca.130 H(2)O (3), [{Cu(6)(mu(3)-OH)(3)(en)(3) (H(2)O)(3)}(B
      alpha-PW(9)O(34))]7 H(2)O (4), [{Ni(6)(mu(3)-OH)(3)(en)(3)(H(2)O)(6)}(B-alpha
      PW(9)O(34))]7 H(2)O (5), [{Ni(6)(mu(3)-OH)(3)(en)(2)(H(2)O)(8)}(B-alpha
      PW(9)O(34))]7 H(2)O (6), [{Ni(6)(mu(3)-OH)(3)(dap)(2)(H(2)O)(8)}(B-alpha
      PW(9)O(34))] 7 H(2)O (7), and [{Ni(6)(mu(3)-OH)(3)(en)(3)(H(2)O)(6)}(B-alpha
      SiW(9)O(34))][Ni(0.5)(en)] 3.5 H(2)O (8) (en=ethylenediamine, dap=1,2
      diaminopropane). These compounds have been structurally characterized by
      elemental analyses, IR spectra, diffuse reflectance spectra, thermogravimatric
      analysis, and X-ray crystallography. The double-cluster complex of
      phosphotungstate 1 simultaneously contains hepta- and hexa-Ni(II)-substituted
      trivacant Keggin units [{Ni(7)(mu(3)-OH)(3)O(2)(dap)(3)(H(2)O)(6)}(B-alpha
      PW(9)O(34))](2-) and [{Ni(6)(mu(3)-OH)(3)(dap)(3)(H(2)O)(6)}(B-alpha
      PW(9)O(34))]. The dimeric silicotungstate 2 is built up from two trivacant Keggin
      [B-alpha-SiW(9)O(34)](10-) fragments linked by an octa-Cu(II) cluster. The main
      skeleton of 3 is a tetrameric cluster constructed from four tri-Fe(III)
      substituted [Fe(III) (3)(mu(3)-OH)(3)(B-alpha-PW(9) O(34))](3-) Keggin units
      linked by a central Fe(II) (4)O(4) cubane core and four mu(4)-PO(4) bridges.
      Complex 4 is an unprecedented three-dimensional extended architecture with
      hexagonal channels built by hexa-Cu(II) clusters and trivacant Keggin [B-alpha
      PW(9)O(34)](9-) fragments. The common feature of 5-8 is that they contain a B
      alpha-isomeric trivacant Keggin fragment capped by a hexa-Ni(II) cluster, very
      similar to the hexa-Ni(II)-substituted trivacant Keggin unit in 1. Magnetic
      measurements illustrate that 1, 2, and 5 have ferromagnetic couplings within the
      magnetic metal centers, whereas 3 and 4 reveal the antiferromagnetic exchange
      interactions within the magnetic metal centers. Moreover, the magnetic behavior
      of 4 and 5 have been theoretically simulated by the MAGPACK magnetic program
      package.

PMID- 18038378
TI  - Sensing the chirality of Dawson lanthanide polyoxometalates [alpha1-LnP2W17O61]7-
      by multinuclear NMR spectroscopy.
AB  - Lanthanide complexes of the chiral Dawson phosphotungstate [alpha(1)
      P(2)W(17)O(61)](10-) were used to study the formation of diastereomers with
      optically pure organic ligands. The present work started with the full assignment
      of the (183)W NMR spectra of [alpha(1)-Yb(H(2)O)(4)P(2)W(17)O(61)](7-) at
      different temperatures and concentrations, which allowed the structure of the
      dimerized form in aqueous solution to be established. Different enantiopure amino
      acids and phosphonic acids were screened as ligands. Both types allowed chiral
      differentiation by multinuclear NMR spectroscopy under fast-exchange conditions.
      Functional groups with a good affinity for the oxo framework of the
      polyoxometalate were identified, and maps of the interactions between L-serine
      and N-phosphonomethyl-L-proline with [alpha(1)-Yb(H(2)O)(4)P(2)W(17)O(61)](7-)
      were established. This demonstrates the power of (183)W NMR spectroscopy to
      elucidate the molecular recognition of inorganic molecules by organic compounds.
      N-Phosphonomethyl-L-proline appears to be a convenient ligand to promote
      separation of the diastereomers and ultimately resolution of the enantiomers of
      [alpha(1)-Yb(H(2)O)(4)P(2)W(17)O(61)](7-).

PMID- 18038379
TI  - Dynamics of electrons in ammonia cages: the discovery system of solvation.
AB  - Two centuries ago solvated electrons were discovered in liquid ammonia and a
      century later the concept of the solvent cage was introduced. Here, we report a
      real time study of the dynamics of size-selected clusters, n=20 to 60, of
      electrons in ammonia, and, for comparison, that of electrons in water cages.
      Unlike the water case, the observed dynamics for ammonia indicates the formation,
      through a 100 fs temperature jump, of a solvent collective motion in a 500 fs
      relaxation process. The agreement of the experimental results-obtained for a well
      defined n, gated electron kinetic energy, and time delay-with molecular dynamics
      theory suggests the critical and different role of the kinetic energy and the
      librational motions involved in solvation.

PMID- 18038380
TI  - Cis-Configured aziridines are new pseudo-irreversible dual-mode inhibitors of
      Candida albicans secreted aspartic protease 2.
AB  - A series of cis-configured epoxides and aziridines containing hydrophobic
      moieties and amino acid esters were synthesized as new potential inhibitors of
      the secreted aspartic protease 2 (SAP2) of Candida albicans. Enzyme assays
      revealed the N-benzyl-3-phenyl-substituted aziridines 11 and 17 as the most
      potent inhibitors, with second-order inhibition rate constants (k(2)) between
      56,000 and 121,000 M(-1) min(-1). The compounds were shown to be pseudo
      irreversible dual-mode inhibitors: the intermediate esterified enzyme resulting
      from nucleophilic ring opening was hydrolyzed and yielded amino alcohols as
      transition-state-mimetic reversible inhibitors. The results of docking studies
      with the ring-closed aziridine forms of the inhibitors suggest binding modes
      mainly dominated by hydrophobic interactions with the S1, S1', S2, and S2'
      subsites of the protease, and docking studies with the processed amino alcohol
      forms predict additional hydrogen bonds of the new hydroxy group to the active
      site Asp residues. C. albicans growth assays showed the compounds to decrease
      SAP2-dependent growth while not affecting SAP2-independent growth.

PMID- 18038381
TI  - Virtual screening and experimental verification to identify potential inhibitors
      of the ErmC methyltransferase responsible for bacterial resistance against
      macrolide antibiotics.
AB  - Methyltransferases from the Erm family catalyze S-adenosyl-L-methionine-dependent
      modification of a specific adenine residue in bacterial 23S rRNA, thereby
      conferring resistance to clinically important macrolide, lincosamide, and
      streptogramin B antibiotics. Thus far, no inhibitors of these enzymes have been
      identified or designed that would effectively abolish the resistance in vivo. We
      used the crystal structure of ErmC' methyltransferase as a target for structure
      based virtual screening of a database composed of 58,679 lead-like compounds.
      Among 77 compounds selected for experimental validation (63 predicted to bind to
      the catalytic pocket and 14 compounds predicted to bind to the putative RNA
      binding site), we found several novel inhibitors that decrease the minimal
      inhibitory concentration of a macrolide antibiotic erythromycin toward an
      Escherichia coli strain that constitutively expresses ErmC'. Eight of them have
      IC(50) values in the micromolar range. Analysis of docking models of the
      identified inhibitors suggests a novel strategy to develop potent and clinically
      useful inhibitors.

PMID- 18038382
TI  - Enantioselective total synthesis of the oral contraceptive desogestrel by a
      double Heck reaction.
AB  - A novel enantioselective total synthesis of the oral contraceptive desogestrel
      (2) is described, in which the tetracyclic steroid core is formed by a sequence
      of two consecutive Heck reactions. Conversion of the known enantiopure diketone 7
      led to the chiral bicycle 6 which was used for a diastereoselective
      intermolecular Heck reaction with vinyliodide 5 to give 15. In the following
      intramolecular Heck reaction, the tetracyclic ring system was formed to give 4,
      from which the synthesis of desogestrel (2) was furnished.

PMID- 18038383
TI  - Synthesis of novel migrastatin and dorrigocin A analogues from D-glucal.
AB  - The synthesis of a range of analogues of the migrastatin macrolide core has been
      achieved from tri-O-acetyl-D-glucal in order to facilitate structure-activity
      studies. Efficient macrolactone formation was achieved in the presence of a
      reactive olefin, by increasing steric hindrance in the olefin environment.
      Acyclic analogues of migrastatin, structurally related to dorrigocin A, have also
      been prepared from D-glucal. The dorrigocin A analogues were prepared using the
      combination of the cross metathesis of ethyl 6-heptenoate with a glycal
      derivative and a subsequent allylic rearrangement-alkene isomerisation reaction
      (Perlin reaction). A synthetic route is thus provided that will enable dorrigocin
      A analogues to be prepared in parallel to migrastatin analogues in the search for
      novel anti-cancer and anti-arthritic therapeutics. Biological evaluation of one
      migrastatin and one dorrigocin A sugar derived analogue show that they inhibit
      proliferation and serum-induced migration of tumour and synovial cells at higher
      concentrations than evodiamine. Dorrigocin A analogues displayed similar potency
      to analogues of the migrastatin core.

PMID- 18038384
TI  - Preferred functionalization of metallic and small-diameter single-walled carbon
      nanotubes by nucleophilic addition of organolithium and -magnesium compounds
      followed by reoxidation.
AB  - Covalent sidewall addition to single-walled nanotubes (SWNTs) of a series of
      organolithium and organomagnesium compounds (nBuLi, tBuLi, EtLi, nHexLi, nBuMgCl,
      tBuMgCl) followed by reoxidation is reported. The functionalized R(n)-SWNTs were
      characterized by Raman and NIR emission spectroscopy. The reaction of SWNTs with
      organolithium and magnesium compounds exhibits pronounced selectivity: in
      general, metallic tubes are more reactive than semiconducting ones. The
      reactivity of SWNTs toward the addition of organometallic compounds is inversely
      proportional to the diameter of the tubes. This was determined simultaneously and
      independently for both metallic and semiconducting SWNTs. The reactivity also
      depends on the steric demands of the addend. Binding of the bulky t-butyl addend
      is less favorable than addition of primary alkyl groups. Significantly, although
      tBuLi is less reactive than, for example, nBuLi, it is less selective toward the
      preferred reaction with metallic tubes. This unexpected behavior is explained by
      fast electron transfer to the metallic SWNTs having low-lying electronic states
      close to the Fermi level, a competitive initial process. The NIR emission of
      weakly functionalized semiconducting SWNTs, also reported for the first time,
      implies interesting applications of functionalized tubes as novel fluorescent
      reporter molecules.

PMID- 18038385
TI  - Catalyst parameters determining activity and selectivity of supported gold
      nanoparticles for the aerobic oxidation of alcohols: the molecular reaction
      mechanism.
AB  - As previously reported for for solventless reactions, gold nanoparticles
      supported on ceria are also excellent general heterogeneous catalysts for the
      aerobic oxidations of alcohols in organic solvents. Among organic solvents it was
      found that toluene is a convenient one. A systematic study on the influence of
      the particle size and gold content on the support has established that the
      activity correlates linearly with the total number of external gold atoms, and
      with the surface coverage of the support. Amongst catalysts with different
      supports, but similar gold particle size and content, gold on ceria exhibits the
      highest activity. By means of a kinetic study (influence of sigma+ parameter,
      kinetic isotopic effect, temperature, alcohol concentration and oxygen pressure)
      a mechanistic proposal consisting of the formation of metal-alcoholate, beta
      hydride shift from carbon to metal and M--H oxidation has been proposed that
      explains all experimental results.

PMID- 18038386
TI  - Solution structure of a DNA duplex containing a biphenyl pair.
AB  - Hydrogen-bonding and stacking interactions between nucleobases are considered to
      be the major noncovalent interactions that stabilize the DNA and RNA double
      helices. In recent work we found that one or multiple biphenyl pairs, devoid of
      any potential for hydrogen bond formation, can be introduced into a DNA double
      helix without loss of duplex stability. We hypothesized that interstrand stacking
      interactions of the biphenyl residues maintain duplex stability. Here we present
      an NMR structure of the decamer duplex d(GTGACXGCAG) d(CTGCYGTCAC) that contains
      one such X/Y biaryl pair. X represents a 3'',5''-dinitrobiphenyl- and Y a 3'',4''
      dimethoxybiphenyl C-nucleoside unit. The experimentally determined solution
      structure shows a B-DNA duplex with a slight kink at the site of modification.
      The biphenyl groups are intercalated side by side as a pair between the natural
      base pairs and are stacked head to tail in van der Waals contact with each other.
      The first phenyl rings of the biphenyl units each show tight intrastrand stacking
      to their natural base neighbors on the 3'-side, thus strongly favoring one of two
      possible interstrand intercalation structures. In order to accommodate the
      biphenyl units in the duplex the helical pitch is widened while the helical twist
      at the site of modification is reduced. Interestingly, the biphenyl rings are not
      static in the duplex but are in dynamic motion even at 294 K.

PMID- 18038388
TI  - Materials in particulate form for tissue engineering. 1. Basic concepts.
AB  - For biomedical applications, materials small in size are growing in importance.
      In an era where 'nano' is the new trend, micro- and nano-materials are in the
      forefront of developments. Materials in the particulate form aim to designate
      systems with a reduced size, such as micro- and nanoparticles. These systems can
      be produced starting from a diversity of materials, of which polymers are the
      most used. Similarly, a multitude of methods are used to produce particulate
      systems, and both materials and methods are critically reviewed here. Among the
      varied applications that materials in the particulate form can have, drug
      delivery systems are probably the most prominent, as these have been in the
      forefront of interest for biomedical applications. The basic concepts pertaining
      to drug delivery are summarized, and the role of polymers as drug delivery
      systems conclude this review.

PMID- 18038389
TI  - Osteoinductive biomaterials--properties and relevance in bone repair.
AB  - The need for bone tissue regeneration is continuously expanding due to the
      improvement of life quality and the consequent increase in life expectancy.
      Although natural bone grafts have shown excellent clinical successes, their use
      is associated with some important drawbacks, limited availability being one of
      the most important. Cell- and growth-factor based tissue engineering provides a
      promising alternative to natural bone grafts; however, the performance of tissue
      engineered constructs often depends on the used carrier. An important challenge
      in the field of bone regeneration is the development of synthetic bone graft
      substitutes that are "intelligent" in that they are able to instruct the in vivo
      environment to form bone. A group of potentially "intelligent" bone graft
      substitutes are osteoinductive biomaterials. In this paper, background on the
      phenomenon of osteoinduction and an overview of synthetic biomaterials with
      osteoinductive potential are given. Furthermore, we elaborate on physicochemical
      properties of biomaterials that are of influence on their osteoinductive
      potential. Finally, we discuss the relevance of osteoinductivity of biomaterials
      in the repair of clinically relevant bone defects.

PMID- 18038390
TI  - Coating bone-like apatite onto organic substrates using solutions mimicking body
      fluid.
AB  - Bone-like apatite is a carbonated hydroxyapatite with a small crystallite and low
      crystallinity. The formation of a layer consisting of bone-like apatite is an
      essential condition for bioactive materials to achieve direct bonding with living
      bone. A bone-like apatite layer can be formed on the surface of organic
      substrates in a solution mimicking a body fluid when some functional groups are
      introduced to organic substrates. This process is a biomimetic process because a
      simulated body fluid and related solutions are used to deposit bone-like apatite
      crystals and promote crystal growth. Coating of bone-like apatite layers through
      biomimetic processes has received much attention in the fabrication of novel
      composites with bone-bonding properties, i.e. bioactivity, and mechanical
      properties analogous to those of living bone tissues. This paper reviews recent
      developments in coating with bone-like apatite layers using biomimetic processes.

PMID- 18038391
TI  - Murine osteoblasts regulate mesenchymal stem cells via WNT and cadherin pathways:
      mechanism depends on cell-cell contact mode.
AB  - Osteoblasts (OSTs) are derived from mesenchymal stem cells (MSCs) and coexist in
      close proximity with MSCs in bone during development and remodelling.
      Interactions between these two cell types remain obscure. Through a well-defined
      co-culture model, the present work demonstrated that OSTs regulate MSCs through
      the WNT and cadherin pathways. The regulation mechanism depends on the cell-cell
      contact mode (indirect or direct) between the two cell types. When physically
      separated (indirect contact), OSTs express WNTs and stimulate the osteogenic
      differentiation of MSCs through the activation of the WNT pathway and suppression
      of the cadherin pathway. This mechanism is evidenced by: (a) the elevation of
      cytoplasmic and nuclear unphosphorylated beta-catenin protein levels; (b) the
      suppression of beta-catenin degradation; (c) the increase in WNT-related
      transcription factor TCF1/LEF1; and (d) the loss of major bone-related cadherins
      (N-CAD and CAD11). Addition of DKK1 antagonizes the WNT pathway and diminishes
      the stimulatory effect of OSTs on MSCs. When in direct cell-cell contact, OSTs
      still secrete WNTs, whose binding still stabilizes the beta-catenin in MSCs.
      However, direct cell-cell contact induces the upregulation of cadherin pathway in
      MSCs, which suppresses the WNT pathway by containing cytoplasmic beta-catenin
      protein at a low level; consequently, the stimulatory effect of OSTs is negated.
      Regulation of cytoplasmic beta-catenin protein levels through concerted action or
      crosstalk between the WNT and cadherin pathways is the key to the signalling
      transduction in these cellular communication networks.

PMID- 18038392
TI  - Multipotent adult progenitor cell transplantation increases vascularity and
      improves left ventricular function after myocardial infarction.
AB  - Progressive contractile dysfunction of viable myocardium that surrounds a large
      infarct leads to heart failure following acute myocardial infarction (AMI).
      Experimental evidence indicates that cellular transplantation may improve the
      left ventricular (LV) contractile performance, even though the underlying
      mechanisms remain undefined. Here, we compared the effect of transplantation of
      murine multipotent adult progenitor cells (MAPCs), a population of adult bone
      marrow-derived cells that differentiate into cells of mesodermal, endodermal and
      ectodermal origin, with murine bone marrow cells (BMCs) or fibroblasts on post
      infarct cardiac function by peri-infarct injection after coronary artery ligation
      in mice. We demonstrate that, in contrast to the other cell populations,
      transplantation of MAPCs significantly improved LV contractile function for at
      least 8 weeks post-transplantation and, although BMCs reduced infarct size, the
      decrease in scar size was substantially greater in MAPC-treated hearts. As
      neither MAPCs nor BMCs were present beyond 1 week, the beneficial effect was not
      due to differentiation and direct contribution of MAPCs to the vascular or
      cardiomyocyte compartment. Significantly more inflammatory cells were present in
      MAPC- than BMC-treated hearts at 1 week, which was accompanied by increased
      vascularity 8 weeks post-transplantation. We hypothesize that MAPCs indirectly
      contributed to these effects, by secreting inflammatory [monocyte chemoattractant
      protein-1 (MCP)-1], and vascular growth factors [vascular endothelial growth
      factor (VEGF), platelet-derived growth factor (PDGF)-BB, and transforming growth
      factor (TGF)beta(1)), and others, resulting in increased angiogenensis and
      cardioprotection.

PMID- 18038393
TI  - The osteogenicity of implanted engineered bone constructs is related to the
      density of clonogenic bone marrow stromal cells.
AB  - Reproducible osteogenicity is a key requirement for the clinical use of bone
      substitutes based on bone marrow stromal cells (BMSCs) and three-dimensional (3D)
      scaffolds. In this study we addressed whether a minimal cell density is required
      for ectopic osteogenicity of constructs generated using a recently developed
      perfusion system for seeding and culturing human BMSCs on 3D scaffolds. Cells
      from human bone marrow aspirates were directly seeded and expanded for 3 weeks
      within the pores of ceramic-based scaffolds, using a perfusion bioreactor. The
      resulting constructs were either implanted subcutaneously in nude mice, to
      determine their capacity to generate bone tissue, or digested to retrieve the
      expanded cells and assess their number, phenotype and clonogenic capacity. The
      final number of BMSCs in the constructs was correlated neither to the initial
      number of seeded cells, nor to the subsequent bone formation. Instead, the final
      number of clonogenic BMSCs in the constructs was positively correlated to the
      initial number of BMSCs seeded, and was significantly higher in osteogenic than
      in non-osteogenic constructs. These results indicate that clonogenic cells play a
      crucial role in determining the osteogenicity of engineered bone substitutes.
      Possible ways to quantify the density of clonogenic cells as a quality control
      parameter to predict potency of BMSC-based constructs are discussed.

PMID- 18038394
TI  - The odontogenic potential of STRO-1 sorted rat dental pulp stem cells in vitro.
AB  - The presence of heterogeneous cell populations in dental pulp may count for the
      considerable variation in the outcome of in vitro and in vivo experiments. Here,
      we intended to determine whether a minor cell sub-population of high
      proliferation and odontogenic potential existed among a larger compartment of
      perhaps more committed progenitors. In this study, the STRO-1 antigen, defining a
      mesenchymal stem cell or progenitor subpopulation, was used for separating rat
      dental pulp cells with fluorescence-activated cell sorting (FACS). Subsequently,
      the STRO-1 positive cells were tested for their ability to differentiate towards
      an odontoblast-like phenotype. Three cell populations (STRO-1 positive, STRO-1
      negative, and non-sorted cells) were cultured in odontogenic medium containing
      dexamethasone and beta-glycerophosphate. Cultures were analyzed by light- and
      scanning electron microscopy (SEM), and assessed for proliferation, ALP activity,
      and calcium content. Results showed that the STRO-1 positive cell population was
      able to differentiate into the odontoblast phenotype, similar to the non-sorted
      population. The negative cells however showed a fibroblast-like phenotype. SEM
      and real-time PCR confirmed such results. In conclusion, the STRO-1 selection
      proved applicable for rat-derived material, to obtain a cell population which is
      more homogeneous. This positive cell fraction was capable of differentiating into
      the odontogenic pathway, whereas the negative fraction was not. However, the
      effect was not always advantageous, when compared to non-sorted cells.

PMID- 18038395
TI  - Repair of articular cartilage defects in the patello-femoral joint with
      autologous bone marrow mesenchymal cell transplantation: three case reports
      involving nine defects in five knees.
AB  - To investigate the effectiveness of autologous culture-expanded bone marrow
      mesenchymal cell transplantation for repairing articular cartilage defects, we
      transplanted autologous culture-expanded bone marrow mesenchymal cells into nine
      full-thickness articular cartilage defects of the patello-femoral joints
      (including two kissing lesions) in the knees of three patients, a 31 year-old
      female, a 44 year-old male and a 45 year-old male. Three weeks before
      transplantation, bone marrow blood was aspirated from the iliac crest. Adherent
      cells were cultured with media containing autologous serum. Single-passaged cells
      were collected, embedded in a collagen solution (5 x 10(6) cells/ml), placed on a
      collagen sheet, gelated, transplanted into the defect and covered with autologous
      periosteum or synovium. Six months after transplantation, the patients' clinical
      symptoms had improved and the improvements have been maintained over the follow
      up periods (17-27 months). Histology of the first patient 12 months after the
      transplantation revealed that the defect had been repaired with the
      fibrocartilaginous tissue. Magnetic resonance imaging of the second patient 1
      year after transplantation revealed complete coverage of the defect, but we were
      unable to determine whether or not the material that covered the defects was
      hyaline cartilage. Autologous bone marrow mesenchymal cells transplantation may
      be an effective approach to promote the repair of articular cartilage defects.

PMID- 18038397
TI  - Engineering tissues, organs and cells.
AB  - Patients suffering from diseased and injured organs may be treated with
      transplanted organs; however, there is a severe shortage of donor organs that is
      worsening yearly, given the ageing population. In the field of regenerative
      medicine and tissue engineering, scientists apply the principles of cell
      transplantation, materials science and bioengineering to construct biological
      substitutes that will restore and maintain normal function in diseased and
      injured tissues. Therapeutic cloning, where the nucleus from a donor cell is
      transferred into an enucleated oocyte in order to extract pluripotent embryonic
      stem cells, offers a potentially limitless source of cells for tissue engineering
      applications. The stem cell field is also advancing rapidly, opening new options
      for therapy, including the use of amniotic and placental fetal stem cells. This
      review covers recent advances that have occurred in regenerative medicine and
      describes applications of these technologies using chemical compounds that may
      offer novel therapies for patients with end-stage organ failure.

PMID- 18038398
TI  - Materials in particulate form for tissue engineering. 2. Applications in bone.
AB  - Materials in particulate form have been the subjects of intensive research in
      view of their use as drug delivery systems. While within this application there
      are still issues to be addressed, these systems are now being regarded as having
      a great potential for tissue engineering applications. Bone repair is a very
      demanding task, due to the specific characteristics of skeletal tissues, and the
      design of scaffolds for bone tissue engineering presents several difficulties.
      Materials in particulate form are now seen as a means of achieving higher control
      over parameters such as porosity, pore size, surface area and the mechanical
      properties of the scaffold. These materials also have the potential to
      incorporate biologically active molecules for release and to serve as carriers
      for cells. It is believed that the combination of these features would create a
      more efficient approach towards regeneration. This review focuses on the
      application of materials in particulate form for bone tissue engineering. A brief
      overview of bone biology and the healing process is also provided in order to
      place the application in its broader context. An original compilation of
      molecules with a documented role in bone tissue biology is listed, as they have
      the potential to be used in bone tissue engineering strategies. To sum up this
      review, examples of works addressing the above aspects are presented.

PMID- 18038399
TI  - A new and evolving paradigm for biocompatibility.
AB  - We propose that the mechanical property of the interface between an implant and
      its surrounding tissues is critical for the host response and the performance of
      the device. The interfacial mechanics depends on several different factors
      related to the physical shape of the device and its surface as well as properties
      of the host tissue and the loading conditions of the device and surrounding
      tissue. It seems plausible that the growth of the fibrotic tissue to support
      mechanical loads is governed by the same principles as depicted by Wolfs' Law for
      bone. Of course, biocompatibility will have different implications depending on
      which vantage point we look at the host-material interface. Another implication
      is that only limited aspects of biocompatibility is measurable with current in
      vitro tests and that the elicited host response in vivo models remains crucial
      for evaluation of medical devices and tissue engineering constructs.

PMID- 18038400
TI  - Self-curing acrylic formulations with applications in intervertebral disk
      restoration: drug release and biological behaviour.
AB  - New injectable acrylic formulations have been prepared to be applied in
      restoration processes for intervertebral disks (IVDs). The solid phase of the
      formulations is composed of poly(methyl methacrylate) (PMMA), incorporating in
      some cases chondroitin sulphate (CS) as a regenerative bioactive molecule,
      whereas the liquid phase is constituted by an amphiphilic macromonomer (MT), 2
      hydroxyethyl methacrylate (HEMA) and, in some formulations, acrylic acid (AA).
      The curing parameters and the mechanical properties of the IVD formulations make
      them excellent candidates for intervertebral application. In vitro and in vivo
      evaluation of the prepared IVD formulations is described in terms of CS release,
      surface analysis after immersion in SBF solutions, and biocompatibility studies
      based on MTT assay and Alamar blue test, as well as in vivo implantation in
      female Wistar rats, by injection of the IVD formulations followed by histological
      evaluations to assess tissue response.

PMID- 18038401
TI  - Multilineage potential of STRO-1+ rat dental pulp cells in vitro.
AB  - The aim of the current study was to determine whether STRO-1 selection is an
      effective approach for purifying rat dental pulp stem cells, and especially
      whether such selection is beneficial on the multilineage differentiation
      capacity, i.e. whether selection will account for a higher rate of
      differentiation or lesser variability. In this study, two cell populations (STRO
      1(+) and non-sorted cells) were cultured under conditions promoting neurogenic,
      adipogenic, myogenic and chondrogenic differentiation. Results of light
      microscopy, histochemistry, and immunohistochemistry showed that STRO-1(+) cells
      were capable of advancing into all four differentiation pathways under the
      influence of inductive media. Quantitative PCR and statistical analysis on
      specific differentiation markers confirmed that there were significant
      upregulations in STRO-1(+) cells compared to the other populations, during
      induction culture. On the basis of our results, we concluded that: (a) rat STRO
      1(+) dental pulp stem cells are capable of differentiating towards multilineage
      cell types, including neural cells, adipocytes, myocytes and chondrocytes; (b)
      the STRO-1(+) population has a more defined multilineage potential compared to
      non-sorted cells, probably because of its more homogeneous nature. .

PMID- 18038402
TI  - Modular tissue engineering: fabrication of a gelatin-based construct.
AB  - Modular tissue-engineered constructs are assembled from sub-millimetre-sized
      cylindrical modules which are seeded with a surface layer of endothelial cells.
      The resulting construct is permeated by a network of interconnected, endothelial
      cell-lined channels to facilitate blood perfusion and nutrient delivery. To
      provide adequate stiffness, yet consist of a substrate suitable for endothelial
      cells, modular constructs were fabricated from gelatin, the denatured form of
      collagen. Gelatin modules containing HepG2 cells or spheroids were fabricated
      using a sieving process. A surface layer of bovine aortic endothelial cells
      completely covering the modules was generated within 1 week of seeding. Modules
      were assembled into constructs within a flow circuit and flow rate-pressure
      difference profiles measured. Fluid perfusion resulted in negligible construct
      compaction, even at high flow rates. It was necessary, however, to crosslink the
      gelatin modules with glutaraldehyde to prevent dissolution at 37 degrees C. This
      resulted in a significant loss of cell viability within the modules. A strategy
      to enable non-toxic crosslinking of the gelatin modules is required to fabricate
      constructs containing viable cells.

PMID- 18038403
TI  - In vitro regulation of adipogenesis: tunable engineered tissues.
AB  - A major clinical challenge in creating a tissue-engineered medical implant is the
      ability to expand cells biopsied from the patient to obtain a clinically relevant
      cell volume. A common tissue engineering strategy involves the culture of
      autologous progenitor cells on biomaterials to form an implantable cellular
      device. However, autologous progenitor cells often lose their differentiation
      potential during the expansion process. The acute regulation of mammary tissue
      expansion in vivo through local modulation of connective tissue suggests that the
      parenchymal-stromal interactions are crucial to develop tissue ex vivo. To better
      understand cellular behaviour in co-culture in two-dimensional systems,
      mesenchymal stem cells were treated with mammary epithelial cell conditioned
      medium and assessed for cell proliferation, lipid production and morphological
      changes over a 17 day culture period. The results showed that bovine epithelial
      cells (MAC-T) are able to inhibit mouse mesenchymal stem cell differentiation
      (D1), even in the presence of adipogenic cocktails. The inhibitory effect is
      reversible, thus potentially providing a mechanism for 'tuning' a cell-based
      device prior to implantation. Further studies found that there were significantly
      higher levels of urokinase plasminogen activator (uPA) and plasminogen activator
      inhibitor 1 (PAI-1) in the MAC-T-conditioned medium than in the murine mammary
      epithelial cell (NMuMG)-conditioned medium, which was not able to inhibit
      adipogenesis of D1 cells. D1 cells are able to proliferate and maintain their
      differentiation potential in MAC-T-conditioned medium. The long-term implication
      is that new culture media may be developed that allow the rapid, clinical
      expansion and differentiation or dedifferentiation of cells for regenerative
      medicine applications.

PMID- 18038404
TI  - Osteogenic differentiation of human adipose-derived stem cells: comparison of two
      different inductive media.
AB  - Human mesenchymal stem cells (MSCs) have the potential to differentiate into
      cells of connective tissue lineages, including bone, cartilage, fat, muscle and
      also neurons. In our study we have examined the phenotypic profile of human
      adipose tissue-derived stem cells (hASCs) and compared different osteogenic
      inductive media to assess hASC differentiation. Cells were enzymatically isolated
      from adipose tissues derived by liposuction from several adult human donors,
      purified and then expanded in culture. We obtained an abundant yield of hASCs
      with a constant proliferative trend, a doubling time of about 68 h and a mild
      variable clonogenic capacity. At passage 4, hASCs expressed MSC-related cell
      surface antigens (CD13, CD105, CD54, CD90, CD44), and subsequently hASCs were
      induced to differentiate into the osteogenic lineage for at least 3 weeks of
      culture in two distinct media, OM1 and OM2, differing in dexamethasone and
      ascorbic acid concentrations. Osteogenic differentiation of OM1- and OM2-cultured
      cells was assessed by evaluating cell morphology, osteopontin expression,
      alkaline phosphatase activity and calcium deposition. OM2 medium showed a higher
      osteogenic potential than OM1, as assessed by increased levels of calcium
      deposition, alkaline phospatase activity and osteopontin expression in comparison
      with OM1-differentiated cells. We conclude that hASCs efficiently differentiate
      into osteogenic lineage, particularly when cultured in inductive medium
      supplemented with 10 nM dexamethasone and 150 microM ascorbic acid.

PMID- 18038405
TI  - Tissue engineering: chondrocyte culture on type 1 collagen support.
      Cytohistological and immunohistochemical study.
AB  - The scope of our study is to evaluate the possibility of cultivating and
      expanding human chondrocytes and seeding them on pure equine type I collagen
      support. Our results show that human articular cartilaginous cells can multiply
      and grow on type I collagen substrate with production of extracellular matrix.
      This type of chondrocyte culture on a support can be used for repairing
      cartilaginous lesions since they show a correct morphology (evaluated by
      cytological and histological methods) and a suitable differentiation and
      phenotype as shown by Alcian PAS staining to indicate the presence of
      mucopolysaccharides, and immunohistochemical methods to identify collagen II. We
      believe that these chondrocyte cultures on this biomaterial can be used for
      repairing cartilaginous lesions with improvement of surgical technique; the
      support allows adhesion of the chondrocytes to the cartilaginous lesion and a
      mallebility that favours optimum spatial adaptation.

PMID- 18038407
TI  - Tissue factor: a mini-review.
AB  - Tissue factor (TF) is historically known as the trigger of the coagulation
      cascade. This integral membrane glycoprotein forms a ternary complex with factor
      VIIa (FVIIa) and zymogen factor (FX), which is then activated to factor Xa (FXa).
      The latter cleaves prothrombin into thrombin (FIIa), which in turn activates
      fibrinogen in fibrin monomers. What is less known is its additional non
      haemostatic roles in inflammation, tumour growth and angiogenesis. This aspect
      will be developed here. TF, as a transmembrane protein, has a signalling effect
      requiring FVIIa. TF-FVIIa complex activates G protein-coupled receptor protease
      activated receptor 2 (PAR-2) and therefore modulates various cellular processes,
      such as cell proliferation and survival, gene transcription and protein
      translation. In this review we will first highlight, using recent structural
      data, the 'potentially' active domain able to modulate the triggered
      intracellular response. We also will focus on the still emerging and promising
      results deciphering the diverse locations in which TF appears. We conclude with a
      description of an emerging and atypical use of tissue factor in platelet gel
      surgery for sinus augmentation.

PMID- 18038408
TI  - Co-culture in cartilage tissue engineering.
AB  - For biotechnological research in vitro in general and tissue engineering
      specifically, it is essential to mimic the natural conditions of the cellular
      environment as much as possible. In choosing a model system for in vitro
      experiments, the investigator always has to balance between being able to
      observe, measure or manipulate cell behaviour and copying the in situ environment
      of that cell. Most tissues in the body consist of more than one cell type. The
      organization of the cells in the tissue is essential for the tissue's normal
      development, homeostasis and repair reaction. In a co-culture system, two or more
      cell types brought together in the same culture environment very likely interact
      and communicate. Co-culture has proved to be a powerful in vitro tool in
      unravelling the importance of cellular interactions during normal physiology,
      homeostasis, repair and regeneration. The first co-culture studies focused mainly
      on the influence of cellular interactions on oocytes maturation to a pre
      implantation blastocyst. Therefore, a brief overview of these studies is given
      here. Later on in the history of co-culture studies, it was applied to study cell
      cell communication, after which, almost immediately as the field of tissue
      engineering was recognized, it was introduced in tissue engineering to study
      cellular interactions and their influence on tissue formation. This review
      discusses the introduction and applications of co-culture systems in cell biology
      research, with the emphasis on tissue engineering and its possible application
      for studying cartilage regeneration.

PMID- 18038409
TI  - A proposed definition of regenerative medicine.
AB  - There exists a lack of consensus regarding a clear and precise definition of
      regenerative medicine. We suggest here a definition developed by the authors with
      input from researchers in the various contributing disciplines. This definition
      emphasizes the interdisciplinarity of the field, its goal of restoring impaired
      function, and the wide variety of technologies that can contribute to achieving
      this goal. By highlighting the lack of agreement regarding a definition of
      regenerative medicine, and by proposing our own definition, we hope to stimulate
      discussion on the subject within the field and to encourage the regenerative
      medicine community to work together to develop a consensus definition. We believe
      that a clear definition of regenerative medicine could help to unify the field
      and is essential to facilitate understanding among policy makers, funding
      agencies and the general public, as well as individuals from scientific and
      medical disciplines.

PMID- 18038410
TI  - New observations of the hierarchical structure of human enamel, from nanoscale to
      microscale.
AB  - Microstructure in terms of hierarchical assembly exists widely in mineralized
      biomaterials, fulfilling an important role in setting up their outstanding
      properties. The purpose of this study was to investigate the hierarchical
      assembly of enamel structure and functions, which are related to the unique
      characteristics of enamel. Human enamel taken from mature third molars was
      explored using scanning electron microscopy (SEM), high-resolution transmission
      electron microscopy (HRTEM) and atomic force microscopy (AFM). Integrating the
      microscopic observations revealed the high complexity of the well-organized
      enamel structure in terms of hierarchical assembly. Based on these observations,
      seven hierarchical levels of the microstructure were proposed and described,
      using a scheme representing a complete spectrum of the organization in detail,
      covering a range from microscale to nanoscale: hydroxyapatite crystals (Level 1)
      at first form mineral nanofibrils (Level 2); the nanofibrils always align
      lengthways, aggregating into fibrils (Level 3) and further thicker fibres (Level
      4); prism/interprism continua (Level 5) are then composed of them. At the
      microscale, prisms assemble into prism bands (Level 6), which present different
      arrangements across the thickness of the enamel layer (Level 7). Analysis of the
      enamel and bone hierarchical structure suggests similarities of scale
      distribution at each level. This study also aimed to understand further the
      structural-mechanical relations at each hierarchical level.

PMID- 18038411
TI  - Ultra-rapid engineered collagen constructs tested in an in vivo nursery site.
AB  - Collagen is a naturally occurring structural protein, highly conserved across
      species. Conventionally, tissue engineering aims to convert cell-seeded
      constructs into a tissue-like architecture with biomimetic function. However,
      cell-mediated remodelling of biomaterial scaffolds in vitro has proved to be
      slow, costly and difficult to control. We have recently developed a novel process
      for ultra-rapid engineering of tissue-like constructs without the need for cell
      based remodelling. Using plastic compression of type I collagen gels, the
      densities of collagen and cells together with mechanical properties can be
      brought controllably to near-tissue levels in minutes rather than weeks/months.
      We have now implanted these constructs in a test site across intercostal spaces
      in a rabbit model designed to provide cyclical tensile loading in vivo, to test
      their integration, cell ingrowth and angiogenic response over 5 weeks. Post
      implanted constructs were recovered and tested for host vascularization,
      inflammatory response and mechanical integrity.

PMID- 18038412
TI  - Potential use of craniosynostotic osteoprogenitors and bioactive scaffolds for
      bone engineering.
AB  - The cranial bone has a very limited regenerative capability. Patients with
      craniosynostosis (the premature fusion of cranial sutures, leading to skull
      abnormalities) often require extensive craniofacial reconstruction and repeated
      surgery. The possibility of grafting autologous osteoprogenitor cells seeded on
      bioabsorbable matrices is of great potential for inducing regeneration of
      craniofacial structure and protecting the brain from external insult. To this
      purpose we have studied the behaviour of normal and craniosynostotic mouse
      osteoblast cell lines, and of human primary osteoprogenitors from
      craniosynostotic patients. We have monitored their ability to grow and
      differentiate on plastic and on a scaffold composed of bioactive glass and
      bioabsorbable polymer by live fluorescent labelling and expression of bone
      differentiation markers. Cells from syndromic patients display a behaviour very
      similar to that observed in the stable mouse cell line we generated by
      introducing the human FGFR2-C278F, a mutation found in certain craniosynostosis,
      into MC3T3 osteblastic cells, indicating that the mutated cell line is a valuable
      model for studying the cellular response of human craniosynostotic osteoblasts.
      Both normal and mutated calvarial osteoprogenitors can attach to the bioactive
      scaffold, although mutated cells display adhesion defects when cultured on
      plastic. Furthermore, analysis of bone differentiation markers in human
      osteoblasts shows that the composite mesh, unlike PLGA(80) plates, supports bone
      differentiation. The ability of the mesh to support homing and differentiation in
      both normal and mutant osteoprogenitors is important, in view of further
      developing autologous biohybrids to repair cranial bone deficits also in
      craniosynostotic patients undergoing extensive reconstructive surgery.

PMID- 18038413
TI  - Effects of surface-modified scaffolds on the growth and differentiation of mouse
      adipose-derived stromal cells.
AB  - PURPOSE: Adipose-derived stromal cells (ADSCs) have been shown to increase
      angiogenesis in ischemic tissue. Maintaining cell survival and facilitating
      angiogenesis in ischemic tissue, however, continues to be the major challenge of
      ADSCs implantation. Recently, bioengineered scaffolds were introduced to support
      and facilitate cell culture and differentiation. The effects of a surface
      modified three-dimensional (3D) scaffold on ADSC function have not been
      investigated. Accordingly, the objective of this study was to determine the
      influence of a gas-plasma treated scaffold on ADSC growth, differentiation into
      endothelial cell, and angiogenic gene expression. METHODS: Freshly isolated mouse
      ADSCs were characterized by flow cytometry and cultured into wells containing gas
      plasma treated scaffolds, non-treated scaffolds, or control wells. Either
      endothelial growth media or differentiation media was used to alter cell
      environment. After 3 and 6 days, cell proliferation was analyzed. VEGF
      concentration in the medium was measured by ELISA. Gene expression was quantified
      by real-time PCR for VEGF receptor-2 (KDR), cyclooxygenase-2 (COX-2) and matrix
      metalloproteinases-2 (MMP-2). RESULTS: ADSCs expressed stem/endothelial
      progenitor markers CD34 and CD133 and endothelial cell marker CD31. ADSCs grew in
      the 3D scaffold. Cells grown on gas-plasma treated scaffolds displayed
      significantly increased expression of VEGF, COX-2, and MMP-2 when grown in
      differentiation but not growth media. When cultured in endothelial growth media,
      VEGF secretion and the expression of KDR, COX-2 and MMP-2 were lower in 3D
      scaffolds than controls. CONCLUSIONS: This study suggests that 3D scaffolds,
      especially gas-plasma treated scaffolds, support ADSC growth and support
      differentiation into endothelial cells.

PMID- 18038414
TI  - Abstracts of the Vascular Matrix Biology and Bioengineering Workshop, March 15
      18, 2007, Whistler, British Columbia, Canada.

PMID- 18038415
TI  - State of the art and future directions of scaffold-based bone engineering from a
      biomaterials perspective.
AB  - Scaffold-based bone tissue engineering aims to repair/regenerate bone defects.
      Such a treatment concept involves seeding autologous osteogenic cells throughout
      a biodegradable scaffold to create a scaffold-cell hybrid that may be called a
      tissue-engineered construct (TEC). A variety of materials and scaffolding
      fabrication techniques for bone tissue engineering have been investigated over
      the past two decades. This review aims to discuss the advances in bone
      engineering from a scaffold material point of view. In the first part the reader
      is introduced to the basic principles of bone engineering. The important
      properties of the biomaterials and the scaffold design in the making of tissue
      engineered bone constructs are discussed in detail, with special emphasis placed
      on the new material developments, namely composites made of synthetic polymers
      and calcium phosphates. Advantages and limitations of these materials are
      analysed along with various architectural parameters of scaffolds important for
      bone tissue engineering, e.g. porosity, pore size, interconnectivity and pore
      wall microstructures.

PMID- 18038416
TI  - Osteochondral defects: present situation and tissue engineering approaches.
AB  - Articular cartilage is often damaged due to trauma or degenerative diseases,
      resulting in severe pain and disability. Most clinical approaches have been shown
      to have limited capacity to treat cartilage lesions. Tissue engineering (TE) has
      been proposed as an alternative strategy to repair cartilage. Cartilage defects
      often penetrate to the subchondral bone, or full-thickness defects are also
      produced in some therapeutic procedures. Therefore, in TE strategies one should
      also consider the need for a simultaneous regeneration of both cartilage and
      subchondral bone in situations where osteochondral defects are present, or to
      provide an enhanced support for the cartilage hybrid construct. In this review,
      different concepts related to TE in osteochondral regeneration will be discussed.
      The focus is on the need to produce new biphasic scaffolds that will provide
      differentiated and adequate conditions for guiding the growth of the two tissues,
      satisfying their different biological and functional requirements.

PMID- 18038417
TI  - Emphasizing the need to more fully understand development: a stem cells and
      regenerative medicine meeting report.
AB  - A shared enthusiasm towards the highly promising utility of stem cell research
      brought together clinicians and scientists from academic institutions,
      government, and industry at the Second Annual International Stem Cells and
      Regenerative Medicine meeting presented by GeneExpression Systems, Inc. earlier
      this year. A common theme was echoed by presenters that a deeper understanding of
      natural development of the whole organism and individual organ systems is needed.
      Armed with this greater knowledge, a more efficient and conscientious translation
      of stem cell research may be achieved. Guest lectures included presentations by
      Dr. Elizabeth H. Blackburn, Dr. Irving L. Weissman, and Dr. Erin Lavik. Attendees
      were updated and encouraged by these and several other speakers on such topics as
      stem cell biology, epigenetics, biotechnology, regenerative medicine, tissue
      engineering, and bioethics. Biomedical engineers and scientists are making steady
      strides in designing specific three dimensional scaffolds, tracking and
      controlling stem cells. The future of stem cell research continues to be
      promising with applications for treating cardiac and neurodegenerative diseases,
      hearing loss, diabetes, and so on.

PMID- 18038418
TI  - The effect of the ionic products of Bioglass dissolution on human osteoblasts
      growth cycle in vitro.
AB  - In this study, in order to observe the effect of Bioglass and its ionic products
      on human esteoblasts growth cycle in vitro, the ionic products of Bioglass have
      been introduced to a cell culture medium by dissolving Bioglass particles in
      Dulbecco's modified Eagle's medium (DMEM) at 37 degrees C for 24 h; this was used
      as the experimental medium, while DMEM without Bioglass modification was used as
      the control medium. Human osteoblasts isolated from trabecular bone were treated
      by the two media and the timing of the osteoblast growth cycle was examined. Cell
      growth curves were derived after 7 days. Also, human osteoblasts were treated for
      1-6 days by the two media, and the G(1), S, G(2) phase percentages of osteoblasts
      were recorded by flow cytometry every day, resulting in the cell proliferation
      activity index: SPF (S-phase fraction) and PI (proliferation index). The
      difference in cell growth was shown after the second day of culture (p < 0.01),
      and cell growth in the experimental groups was greater than in control groups.
      The SPF and PI of the experimental groups were also higher than the control
      groups in 2 days of culture (p < 0.05 and p < 0.01), which indicates that the
      growth cycle of the human osteoblasts in experimental medium is about 2 days. In
      conclusion, Bioglass can promote osteoblast proliferation, reducing the human
      osteoblast growth cycle to pass through G(1) and S phase and then enter G(2)
      phase quickly.

PMID- 18038419
TI  - Spatial differences of cellular origins and in vivo hypoxia modify contractile
      properties of pulmonary artery smooth muscle cells: lessons for arterial tissue
      engineering.
AB  - Tissue engineering of functional arteries is challenging. Within the pulmonary
      artery wall, smooth muscle cells (PASMCs) have site-specific developmental and
      functional phenotypes, reflecting differing contractile roles. The force
      generated by PASMCs isolated from the inner 25% and outer 50% of the media of
      intrapulmonary elastic arteries from five normal and eight chronically hypoxic
      (hypertensive) 14 day-old piglets was quantified in a three-dimensional (3D)
      collagen construct, using a culture force monitor. Outer medial PASMCs from
      normal piglets exerted more force (528 +/- 50 dynes) than those of hypoxic
      piglets (177 +/- 42 dynes; p < 0.01). Force generation by inner medial PASMCs
      from normal and hypoxic piglets was similar (349 +/- 35 and 239 +/- 60 dynes). In
      response to agonist (thromboxane) stimulation, all PASMCs from normal and hypoxic
      piglets contracted, but the increase in force generated by outer and inner
      hypoxic PASMCs (ranges 13-72 and 14-56 dynes) was less than by normal PASMCs
      (ranges 27-154 and 34-159 dynes, respectively; p < 0.05 for both). All hypoxic
      PASMCs were unresponsive to antagonist (sodium nitroprusside) stimulation, all
      normal PASMCs relaxed (range - 87 to - 494 dynes). Myosin heavy chain expression
      by both hypoxic PASMC phenotypes was less than normal (p < 0.05 for both), as was
      the activity of focal adhesion kinase, regulating contraction, in hypoxic inner
      PASMCs (p < 0.01). Chronic hypoxia resulted in the development of abnormal PASMC
      phenotypes, which in collagen constructs exhibited a reduction in contractile
      force and reactivity to agonists. Characterization of the mechanical response of
      spatially distinct cells and modification of their behaviour by hypoxia is
      critical for successful tissue engineering of major blood vessels.

PMID- 18038421
TI  - Enhancement of osteoblastic differentiation of mesenchymal stromal cells cultured
      by selective combination of bone morphogenetic protein-2 (BMP-2) and fibroblast
      growth factor-2 (FGF-2).
AB  - It is well known that bone marrow contains mesenchymal stromal cells (MSCs),
      which can show osteoblastic differentiation when cultured in osteogenic medium
      containing ascorbic acid, beta-glycerophosphate and dexamethasone. The
      differentiation results in the appearance of osteoblasts, together with the
      formation of bone matrix; thus, in vitro cultured bone (osteoblasts/bone matrix)
      could be fabricated by MSC culture. This type of cultured bone has already been
      used in clinical cases involving orthopaedic problems. To improve the therapeutic
      effect of the cultured bone, we investigated the culture conditions that
      contributed to extensive osteoblastic differentiation. Rat bone marrow was
      primarily cultured to expand the number of MSCs and further cultured in
      osteogenic medium for 12 days. The culture was also conducted in a medium
      supplemented with either bone morphogenetic protein-2 (BMP-2) or fibroblast
      growth factor (FGF-2), or with sequential combinations of both supplements. Among
      them, the sequential supplementation of FGF-2 followed by BMP-2 showed high
      alkaline phosphatase activity, sufficient bone-specific osteocalcein expression
      and abundant bone matrix formation of the MSC culture. These data implied that
      the number of responding cells or immature osteoblasts was increased by the
      supplementation of FGF-2 in the early phase of the culture and that these cells
      can show osteoblastic differentiation, of which capability was augmented by BMP-2
      in the late phase. The sequential supplementation of these cytokines into MSC
      culture might be suitable for the fabrication of ideal cultured bone for use in
      bone tissue engineering.

PMID- 18038423
TI  - Vascular tissue engineering with magnetic nanoparticles: seeing deeper.
AB  - The endothelium bares a paramount therapeutic and diagnostic significance in
      vascular disease. The current work presents a novel strategy based on the use of
      superparamagnetic nanoparticles to obtain an endothelial cell lining on the
      luminal surface of vascular conduits, which can be detected non-invasively in a
      clinical Magnetic Resonance Imaging (MRI) scanner. Human umbilical vein
      endothelial cells (HUVECs) were prelabeled with clinically approved
      superparamagnetic nanoparticles. Cell viability and eNOS expression were not
      affected by the labelling procedure. Magnetically labelled cells were delivered
      onto the lumen of a PTFE tubular graft by a customised electromagnet. The
      endothelium was detected in a 1,5T MRI scanner. Magnetic cell delivery provides
      an efficient technique to seed tubular scaffolds enabling the non-invasive
      depiction of the cells from the substrate, thus providing a reliable tool to
      assess the quality of cell delivery procedures.

PMID- 18038420
TI  - Isolation and characterization of mesenchymal cells from human fetal membranes.
AB  - Bone marrow (BM) multipotent mesenchymal stromal cells (MSCs) present with
      multipotent differentiation potential and immunomodulatory properties. As an
      alternative to bone marrow, we have examined fetal membranes, amnion and chorion,
      of term human placenta as a potential source of multipotent MSCs. Here we show
      that amnion mesenchymal cells (AMCs) and chorion mesenchymal cells (CMCs),
      isolated by mechanical separation and subsequent enzymatic digestion, demonstrate
      plastic adherence and fibroblast-like morphology and are able to form colonies
      that could be expanded for at least 15 passages. By FACS analysis, AMCs and CMCs
      were shown to be phenotypically similar to BM-MSCs and, when cultured in
      differentiation media, they demonstrated high morphogenetic plasticity by
      differentiating into osteocytes, chondrocytes and adipocytes. In an attempt to
      isolate cells with MSC characteristics from human fetal membranes, AMCs and CMCs
      expressing CD271 were enriched by immunomagnetic isolation and were demonstrated
      to possess higher clonogenic and osteogenic differentiation potential than CD271
      depleted fractions. Based on these findings, amnion and chorion can be considered
      as a novel and convenient source of adult MSCs.

PMID- 18038422
TI  - Cellular delivery of TGFbeta1 promotes osteoinductive signalling for bone
      regeneration.
AB  - Administration of osteoinductive growth factors to wound sites, alone or in
      conjunction with a delivery vehicle, is an appealing treatment option for
      critical bone defects. The delivery of cells transfected with genes encoding for
      osteoinductive growth factors, such as TGFbeta(1), represents an attractive
      option to locally deliver constant levels of these growth factors to stimulate
      new bone formation at the defect site. Using non-viral transfection methods, we
      showed that osteoblasts can be genetically modified in vitro to secrete sustained
      therapeutic levels of TGFbeta(1) in its active form through control of the
      transfected cell environment. In addition, delivery of TGFbeta(1) produced by
      genetically modified cells that contained the proper post-translational
      modifications provided a more robust cellular response compared to administration
      of bacterially-derived recombinant TGFbeta(1). Migration and subsequent
      proliferation of osteoblasts are critical aspects of the initial steps in the
      cascade of new bone tissue formation. Exposure to mammalian-derived TGFbeta(1)
      induced a more pronounced chemotactic response upon administration of 10 pg/ml
      TGFbeta(1), whereas osteoblasts showed enhanced levels of metabolic activity at
      100 pg/ml, which is indicative of greater levels of cellular proliferation when
      compared to addition of the same levels of recombinant TGFbeta(1). This increased
      efficacy of cell-derived TGFbeta(1) over recombinant forms of TGFbeta(1),
      combined with provision of a continual source of TGFbeta(1), highlights the
      advantages of delivering genetically modified cells over exogenous protein
      delivery for bone tissue engineering.

PMID- 18038424
TI  - Cryopreservation characteristics of adipose-derived stem cells: maintenance of
      differentiation potential and viability.
AB  - With the emergence of regenerative medicine, many researchers have turned to fat
      tissue as a source of adipose-derived stem cells (ASCs). Because freshly
      collected adipose tissue is not always readily available, there will be a need
      for improved cryopreservation methods to reproducibly maintain ASC viablility and
      multipotentiality in long-term storage. This study examines the efficiency of
      conventional dimethyl sulphoxide cryopreservation methods by measuring the
      maintenance of differentiation potential after one freeze cycle. Additionally, we
      analysed the viability of ASCs as a function of varying cell concentrations in
      cryopreservation media. We evaluated four distinct colony-forming unit assays
      (fibroblast, alkaline phosphatase, adipocyte and osteoblast) to monitor
      quantitatively the differentiation potential in ASCs after one freeze cycle. We
      found that the post-thaw viability was a function of storage concentration and
      that an optimal viability was observed for a concentration of 0.5 x 10(6)
      cells/ml cryopreservation medium.

PMID- 18038427
TI  - Myocardial tissue engineering: a review.
AB  - Myocardial tissue engineering, a concept that intends to overcome the obstacles
      to prolonging patients' life after myocardial infarction, is continuously
      improving. It comprises a biomaterial based 'vehicle', either a porous scaffold
      or dense patch, made of either natural or synthetic polymeric materials, to aid
      transportation of cells into the diseased region in the heart. Many different
      cell types have been suggested for cell therapy and myocardial tissue
      engineering. These include both autologous and embryonic stem cells, both having
      their advantages and disadvantages. Biomaterials suggested for this specific
      tissue-engineering application need to be biocompatible with the cardiac cells
      and have particular mechanical properties matching those of native myocardium, so
      that the delivered donor cells integrate and remain intact in vivo. Although much
      research is being carried out, many questions still remain unanswered requiring
      further research efforts. In this review, we discuss the various approaches
      reported in the field of myocardial tissue engineering, focusing on the
      achievements of combining biomaterials and cells by various techniques to repair
      the infarcted region, also providing an insight on clinical trials and possible
      cell sources in cell therapy. Alternative suggestions to myocardial tissue
      engineering, in situ engineering and left ventricular devices are also discussed.

PMID- 18038428
TI  - Cost-effectiveness analysis at the development phase of a potential health
      technology: examples based on tissue engineering of bladder and urethra.
AB  - OBJECTIVES: We demonstrate the use of health economics to guide investment
      decisions in regenerative medicine. Our examples are based on proposed tissue
      engineering applications in the urinary tract. We show that health economics have
      a role in strengthening the supply side, not just the demand side of the health
      economy. METHODS: We reviewed the epidemiology and treatment of the clinical
      conditions where TE of urothelium may be considered using literature identified
      from a range of sources including electronic databases, article bibliographies
      and references, online articles and expert opinion in the field. RESULTS: Careful
      analysis of current best treatment suggested that urethral defects and bladder
      resection for cancer offered the most propitious applications of TE. The headroom
      for engineered urethral tissue was estimated at pound sterling186. This is
      unlikely to be large enough to support the launch of a TE product populated with
      viable cells. The headroom for TE bladder, on the other hand, was estimated at
      around pound sterling16 268. However, the market size is limited reducing
      potential profitability. CONCLUSIONS: The Headroom Method can help inform
      instrumental decisions concerning new treatments without having to build a
      complex model with very wide parameter uncertainty.

PMID- 18038429
TI  - Time-course study of histological and genetic patterns of differentiation in
      human engineered oral mucosa.
AB  - The lack of sufficient oral mucosa available for intra-oral grafting is a major
      surgical problem, and new sources of oral tissues for clinical use are needed. In
      this regard, some models of engineered oral mucosa have been reported to date,
      but little is known about the structural and genetic mechanisms that occur during
      the process of development and maturation of these tissue substitutes. We have
      carried out a time-course study of the genes and morphological patterns of cell
      and tissue differentiation that develop in oral mucosa constructs after 3, 7, 11
      and 21 days of development. Our electron microscopy and microarray analyses
      demonstrated that the oral mucosa constructs generated by tissue engineering
      undergo a progressive process of cell differentiation with the sequential
      formation and maturation of several layers of epithelium (with expression of
      stratifin, sciellin, involucrin, trichohyalin and kallikrein 7), intercellular
      junctions (with expression of plakophilin, desmocollin, desmoglein and
      cadherins), cytokeratins, a basement membrane (laminins, collagen IV) and the
      extracellular matrix (biglycan, matrix metalloproteinases). In conclusion,
      although the level and type of keratinization developed in vitro could be
      different, the oral mucosa substitutes were very similar to the native tissues.

PMID- 18038430
TI  - GDNF-chitosan blended nerve guides: a functional study.
AB  - Nerve guides are currently being fabricated by blending a variety of biomaterials
      with different proteins. Adding proteins, which can support nerve repair and
      regeneration, optimizes the biological properties of a nerve guide. In our study
      we have blended glial cell line-derived nerve growth factor (GDNF) and laminin
      with chitosan to fabricate GDNF-laminin blended chitosan (GLC) nerve guides. As
      GDNF is known to provide trophic support to motor neurons, the main objective of
      this study was assess the functional restoration of an injured sciatic nerve
      treated with GLC. Functional nerve recovery was evaluated using a video gait
      analysis technique. Gastrocnemius muscle weight measurements and sensitivity
      testing were correlated to functional nerve recovery. Our results indicate an
      increase in the functional recovery of the GLC group when compared to the
      unblended chitosan nerve guides. At the end of 12 weeks, GLC nerve guides had
      comparable functional values to the Laminin-I blended chitosan nerve guides (LC)
      and autograft groups, which were both significantly higher at the terminal stance
      phase angle as compared to the unblended chitosan nerve guides. Muscle weights
      for the GLC group indicated decreased atrophy and restoration of functional
      strength, compared to the unblended chitosan groups. In addition, behavioural
      testing demonstrated that the GLC group regained sensation while the control
      groups displayed no restoration. Thus, the addition of GDNF and laminin to the
      chitosan nerve guides enhanced both functional and sensory recovery.

PMID- 18038431
TI  - Cholic acid functionalized star poly(DL-lactide) for promoting cell adhesion and
      proliferation.
AB  - Cholic acid functionalized star poly(DL-lactide) was synthesized through the ring
      opening polymerization of DL-lactide initiated by cholic acid. The properties and
      cell behaviour of the cholic acid functionalized star poly(DL-lactide) were
      investigated as compared with linear poly(DL-lactide)s with different molecular
      weights and a star poly(DL-lactide) initiated by glycerol. In comparison to
      linear poly(DL-lactide)s, the cholic acid functionalized star poly(DL-lactide)
      had better wettability and slightly higher surface energy. The cell adhesion and
      proliferation on different materials were evaluated using two types of cells, 3T3
      mouse fibroblasts and ECV304 human endothelial cells. Compared with the linear
      poly(DL-lactide)s, the cholic acid functionalized star poly(DL-lactide) showed
      obviously improved property for cell adhesion. The cell proliferation on the
      cholic acid functionalized star poly(DL-lactide) was also enhanced. The
      improvement in cell proliferation was not so significant as compared with the
      improvement in cell adhesion. This modification strategy provides an effective
      and simple way to promote cell attachment and growth in tissue engineering.

PMID- 18038432
TI  - Smart and cationic poly(NIPA)/PEI block copolymers as non-viral vectors: in vitro
      and in vivo transfection studies.
AB  - In this study, in vitro and in vivo transfection of temperature-sensitive,
      polycationic poly(N-isopropylacrylamide) and polyethyleneimine copolymers
      (poly(NIPA)/PEI25L) were performed. Copolymer and copolymer-plasmid DNA (pDNA)
      complexes were positively charged as + 7.6 and + 12.8, respectively. Gel
      retardation assay confirmed good complex formation and release of plasmid DNA in
      response to temperature and pH. Cytotoxicity tests showed at least 80% smooth
      muscle cell (SMC) viability. The uptake of the complexes by SMCs was quite high;
      however, the best gene expression efficiency achieved with the copolymeric
      vectors was about 30% with the complex prepared with a polymer:plasmid ratio of
      6. Gene expression efficiency was enhanced up to 50% by changing the temperature
      from 37 degrees C to 28 degrees C. Preliminary in vivo studies were performed
      above and below lower critical solution temperature (LCST) in lung, heart, liver,
      kidney, muscle and also subcutaneously in 5 week-old mice. The gene expression
      ratio was higher in lung, tibial muscle and subcutaneously than in other tissues
      (heart, liver and kidney) above LCST. Then, temperature decrease caused an
      increase in the amount of gene expression in tibial muscle and subcutaneously,
      revealing the contribution of temperature-sensitivity on DNA release and gene
      expression.

PMID- 18038433
TI  - Vascular tissue generation in response to signaling molecules integrated with a
      novel poly(epsilon-caprolactone)-fibrin hybrid scaffold.
AB  - A major constraint in the use of biodegradable polymer scaffolds for vascular
      tissue engineering is poor cell adhesion and lack of signals for new tissue
      generation. The presence of extracellular matrix (ECM) within the scaffold is
      desirable for growth of endothelial cells and in vitro formation of remodelled
      vascular conduit. In this study, we have produced a hybrid scaffold by coating
      porous poly-caprolactone (PCL) film with biomimetic ECM components consisting of
      fibrin, gelatin, fibronectin, angiogenic growth factors and proteoglycans. Human
      umbilical vein endothelial cells (HUVECs) adhered, spread, proliferated and
      survived for long periods in culture on the hybrid scaffold. As compared to bare
      PCL, enhanced cell adhesion, spreading and cytoskeletal organization were
      demonstrated on the hybrid scaffold, using confocal microscopy of EC-actin
      stained with Texas red-conjugated phalloidin. Population doubling of endothelial
      cells (ECs) on the hybrid scaffold and bare scaffold was estimated as 42 h and
      136 h, respectively, as assessed by a 3H-thymidine uptake method. Analysis of
      proliferating cell nuclear antigen (PCNA) also indicated low proliferation on
      bare scaffold. Flow cytometric analysis of annexin V-stained cells showed poor
      survival of ECs on bare PCL as compared to the hybrid scaffold. Deposition of
      insoluble collagen and elastin was identified on the hybrid scaffold by cells
      recovered after 15 days and 30 days of EC culture, using fluorochrome-tagged
      specific antibodies and confocal microscopy, and the fluorescence intensity
      corresponding to elastin and collagen after 30 days was similar to that of 15
      days. The results indicate that ECM deposition by endothelial cells is a
      regulated process without excessive accumulation after 30 days.

PMID- 18038434
TI  - Cytokine and chemokine dynamics differ between rats and mice after collagen
      implantation.
AB  - Implanted scaffold materials induce an inflammatory reaction known as the
      'foreign body reaction' (FBR). We hypothesized that the observed difference in
      FBR between rats and mice correlate with different expression dynamics of
      cytokines and chemokines, which are key orchestrators of the FBR. After
      implantation of hexamethylene diisocyanate cross-linked dermal sheep collagen,
      the overall gene expression pattern of IL-1, IL-6, IL-10, TNFalpha, CXCL1/KC,
      CXCL2/MIP2 and CCL2/MCP1 was roughly similar for the two species. During the
      onset of the FBR these genes were maximally expressed in rats and mice, after
      which the expression decreased to basal levels. The expression of CCL3/MIP1 alpha
      had a similar course, yet it increased after the progression phase of the FBR in
      both species. The expression of cytokines and chemokines in sham-operated animals
      was low throughout, showing that the implanted material by itself exerted the
      changes in gene expression of the invading cells. During the progression, genes
      encoding the PMN attractants CXCL1/KC and CXCL2/MIP2 were more highly expressed
      in mice than in rats, which would explain the prolonged presence of PMNs in mice
      during the FBR. Additionally, the strong induction of IFN gamma in rats coincided
      with a higher phagocytotic activity by macrophages. Throughout the FBR, the
      expression of TGFbeta was constitutive and high in both species, but increased in
      mice during the progression phase. This could explain the extensive stroma
      formation during the murine FBR. Unexpectedly, the stronger expression of
      TNFalpha and CCL3/MIP1 alpha in mice, did not result in high macrophage
      attraction or phagocytosis of the implanted collagen disks.

PMID- 18038435
TI  - Bacterial cellulose as a potential meniscus implant.
AB  - Traumatic or degenerative meniscal lesions are a frequent problem. The meniscus
      cannot regenerate after resection. These lesions often progress and lead to
      osteoarthritis. Collagen meniscal implants have been used in clinical practice to
      regenerate meniscal tissue after partial meniscectomy. The mechanical properties
      of bacterial cellulose (BC) gel were compared with a collagen material and the
      pig meniscus. BC was grown statically in corn steep liquid medium, as described
      elsewhere. Pig meniscus was harvested from pigs. The collagen implant was packed
      in sterile conditions until use. The different materials were evaluated under
      tensile and compression load, using an Instron 5542 with a 500 N load cell. The
      feasibility for implantation was explored using a pig model. The Young's modulus
      of bacterial cellulose was measured to be 1 MPa, 100 times less for the collagen
      material, 0.01 MPa in tensile load. The Young's modulus of bacterial cellulose
      and meniscus are similar in magnitude under a compression load of 2 kPa and with
      five times better mechanical properties than the collagen material. At higher
      compression strain, however, the pig meniscus is clearly stronger. These
      differences are clearly due to a more ordered and arranged structure of the
      collagen fibrils in the meniscus. The combination of the facts that BC is
      inexpensive, can be produced in a meniscus shape, and promotes cell migration
      makes it an attractive material for consideration as a meniscus implant.

PMID- 18038437
TI  - Oxidant-free alcohol dehydrogenation using a reusable hydrotalcite-supported
      silver nanoparticle catalyst.

PMID- 18038438
TI  - Eutectic gallium-indium (EGaIn): a moldable liquid metal for electrical
      characterization of self-assembled monolayers.

PMID- 18038439
TI  - One-pot multicomponent synthesis of indoles from 2-iodobenzoic acid.

PMID- 18038440
TI  - Increasing the complexity of periodic protein nanostructures by the rolling
      circle-amplified synthesis of aptamers.

PMID- 18038441
TI  - Relative rates of bromine-magnesium exchange reactions in substituted
      bromobenzene derivatives.

PMID- 18038442
TI  - Highly efficient catalytic system for enantioselective Michael addition of
      aldehydes to nitroalkenes in water.

PMID- 18038443
TI  - Mercury-alkyl bond cleavage based on organomercury lyase.

PMID- 18038444
TI  - On the origin of the haouamine alkaloids.

PMID- 18038445
TI  - A likelihood reformulation method in non-normal random effects models.
AB  - In this paper, we propose a practical computational method to obtain the maximum
      likelihood estimates (MLE) for mixed models with non-normal random effects. By
      simply multiplying and dividing a standard normal density, we reformulate the
      likelihood conditional on the non-normal random effects to that conditional on
      the normal random effects. Gaussian quadrature technique, conveniently
      implemented in SAS Proc NLMIXED, can then be used to carry out the estimation
      process. Our method substantially reduces computational time, while yielding
      similar estimates to the probability integral transformation method (J. Comput.
      Graphical Stat. 2006; 15:39-57). Furthermore, our method can be applied to more
      general situations, e.g. finite mixture random effects or correlated random
      effects from Clayton copula. Simulations and applications are presented to
      illustrate our method.

PMID- 18038446
TI  - A critical appraisal of propensity-score matching in the medical literature
      between 1996 and 2003.
AB  - Propensity-score methods are increasingly being used to reduce the impact of
      treatment-selection bias in the estimation of treatment effects using
      observational data. Commonly used propensity-score methods include covariate
      adjustment using the propensity score, stratification on the propensity score,
      and propensity-score matching. Empirical and theoretical research has
      demonstrated that matching on the propensity score eliminates a greater
      proportion of baseline differences between treated and untreated subjects than
      does stratification on the propensity score. However, the analysis of propensity
      score-matched samples requires statistical methods appropriate for matched-pairs
      data. We critically evaluated 47 articles that were published between 1996 and
      2003 in the medical literature and that employed propensity-score matching. We
      found that only two of the articles reported the balance of baseline
      characteristics between treated and untreated subjects in the matched sample and
      used correct statistical methods to assess the degree of imbalance. Thirteen (28
      per cent) of the articles explicitly used statistical methods appropriate for the
      analysis of matched data when estimating the treatment effect and its statistical
      significance. Common errors included using the log-rank test to compare Kaplan
      Meier survival curves in the matched sample, using Cox regression, logistic
      regression, chi-squared tests, t-tests, and Wilcoxon rank sum tests in the
      matched sample, thereby failing to account for the matched nature of the data. We
      provide guidelines for the analysis and reporting of studies that employ
      propensity-score matching.

PMID- 18038447
TI  - A discrete-continuous mixture quantile function estimator with a practical
      application to phase II cancer clinical trials.
AB  - Oftentimes in biological and clinical settings an underlying continuous variable
      or discrete-continuous mixture is dichotomized in order to interpret the results
      in a simpler fashion. Tests of interest are then typically based on exact
      binomial tests. In this article, we illustrate the utility of a new quantile
      based approach towards testing the same basic scientific question in terms of
      improved relative efficiency and similar ease of interpretation when compared
      with the binomial test. We illustrate the utility of our approach with an eye
      towards mixtures of discrete-continuous data commonly found in phase II cancer
      clinical trial data.

PMID- 18038448
TI  - Can chemotherapy induce reactions of recollection?

PMID- 18038449
TI  - Ethanol induces oxidative stress in primary rat hepatocytes through the early
      involvement of lipid raft clustering.
AB  - The role of the hepatocyte plasma membrane structure in the development of
      oxidative stress during alcoholic liver diseases is not yet fully understood.
      Previously, we have established the pivotal role of membrane fluidity in ethanol
      induced oxidative stress, but no study has so far tested the involvement of lipid
      rafts. In this study, methyl-beta-cyclodextrin or cholesterol oxidase, which were
      found to disrupt lipid rafts in hepatocytes, inhibited both reactive oxygen
      species production and lipid peroxidation, and this suggested a role for these
      microstructures in oxidative stress. By immunostaining of lipid raft components,
      a raft clustering was detected in ethanol-treated hepatocytes. In addition, we
      found that rafts were modified by formation of malondialdehyde adducts and
      disulfide bridges. Interestingly, pretreatment of cells by 4-methyl-pyrazole (to
      inhibit ethanol metabolism) and various antioxidants prevented the ethanol
      induced raft aggregation. In addition, treatment of hepatocytes by a stabilizing
      agent (ursodeoxycholic acid) or a fluidizing compound [2-(2-methoxyethoxy)ethyl 8
      (cis-2-n-octylcyclopropyl)octanoate] led to inhibition or enhancement of raft
      clustering, respectively, which pointed to a relationship between membrane
      fluidity and lipid rafts during ethanol-induced oxidative stress. We finally
      investigated the involvement of phospholipase C in raft-induced oxidative stress
      upon ethanol exposure. Phospholipase C was shown to be translocated into rafts
      and to participate in oxidative stress by controlling hepatocyte iron content.
      CONCLUSION: Membrane structure, depicted as membrane fluidity and lipid rafts,
      plays a key role in ethanol-induced oxidative stress of the liver, and its
      modulation may be of therapeutic relevance.

PMID- 18038450
TI  - Stabilization of beta-catenin affects mouse embryonic liver growth and
      hepatoblast fate.
AB  - During hepatogenesis, after the liver has budded out of the endoderm, the
      hepatoblasts quickly expand and differentiate into either hepatocytes or biliary
      cells, the latter of which arise only within the ductal plate surrounding the
      portal vein. Because the Wnt/beta-catenin pathway is involved in liver
      homeostasis and regeneration and in liver carcinogenesis, we investigated here a
      role for Wnt/beta-catenin signaling in the embryonic liver. A cyclization
      recombination (Cre)/locus of X-over P1 (loxP) strategy was chosen to perform
      adenomatous polyposis coli (Apc) invalidation in order to activate ectopic beta
      catenin signaling in hepatoblasts; an appropriate transgenic model expressing the
      Cre recombinase was used. Phenotypic and immunolocalization studies, together
      with messenger RNA analyses, by microarray and real-time quantitative polymerase
      chain reaction approaches were performed on this model during normal
      hepatogenesis. The loss of Apc allowed beta-catenin activation in the
      hepatoblasts after the formation of the liver bud and led to embryonic lethality.
      In this model, the liver became hypoplastic, and hepatocyte differentiation
      failed, whereas beta-catenin-activated ducts developed and gave rise to fully
      differentiated bile ducts when transplanted into adult recipient livers.
      Microarray analyses suggested that beta-catenin plays a role in repressing the
      hepatocyte genetic program and remodeling the ductal plate. According to these
      data, in normal embryonic livers, beta-catenin was transiently activated in the
      nascent bile ducts. CONCLUSION: We demonstrated a key role for the Wnt/beta
      catenin pathway in liver embryonic growth and in controlling the fate of
      hepatoblasts, preventing them from differentiating toward the hepatocyte lineage,
      and guiding them to biliary ductal morphogenesis.

PMID- 18038451
TI  - Peroxisome proliferator-activated receptor-beta/delta protects against chemically
      induced liver toxicity in mice.
AB  - Potential functional roles for the peroxisome proliferator-activated receptor
      beta/delta (PPARbeta/delta) in skeletal muscle fatty acid catabolism and
      epithelial carcinogenesis have recently been described. Whereas PPARbeta/delta is
      expressed in liver, its function in this tissue is less clear. To determine the
      role of PPARbeta/delta in chemically induced liver toxicity, wild-type and
      PPARbeta/delta-null mice were treated with azoxymethane (AOM) and markers of
      liver toxicity examined. Bile duct hyperplasia, regenerative hyperplasia, and
      increased serum alanine aminotransferase (ALT) were found in AOM-treated
      PPARbeta/delta-null mice, and these effects were not observed in similarly
      treated wild-type mice. Exacerbated carbon tetrachloride (CCl(4)) hepatoxicity
      was also observed in PPARbeta/delta-null as compared with wild-type mice. No
      differences in messenger RNAs (mRNAs) encoding cytochrome2E1 required for the
      metabolic activation of AOM and CCl(4) were observed between wild-type or
      PPARbeta/delta-null mice in response to CCl(4). Significant differences in the
      expression of genes reflecting enhanced nuclear factor kappa B (NF-kappaB)
      activity were noted in PPARbeta/delta-null mice. CONCLUSION: Results from these
      studies show that PPARbeta/delta is protective against liver toxicity induced by
      AOM and CCl(4), suggesting that this receptor is hepatoprotective against
      environmental chemicals that are metabolized in this tissue.

PMID- 18038452
TI  - Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating
      the European Liver Fibrosis Panel and exploring simple markers.
AB  - The detection of fibrosis within nonalcoholic fatty liver disease (NAFLD) is
      important for ascertaining prognosis and the stratification of patients for
      emerging therapeutic intervention. We validated the Original European Liver
      Fibrosis panel (OELF) and a simplified algorithm not containing age, the Enhanced
      Liver fibrosis panel (ELF), in an independent cohort of patients with NAFLD.
      Furthermore, we explored whether the addition of simple markers to the existing
      panel test could improve diagnostic performance. One hundred ninety-six
      consecutively recruited patients from 2 centers were included in the validation
      study. The diagnostic accuracy of the discriminant scores of the ELF panel,
      simple markers, and a combined panel were compared using receiver operator
      curves, predictive values, and a clinical utility model. The ELF panel had an
      area under the curve (AUC) of 0.90 for distinguishing severe fibrosis, 0.82 for
      moderate fibrosis, and 0.76 for no fibrosis. Simplification of the algorithm by
      removing age did not alter diagnostic performance. Addition of simple markers to
      the panel improved diagnostic performance with AUCs of 0.98, 0.93, and 0.84 for
      the detection of severe fibrosis, moderate fibrosis, and no fibrosis,
      respectively. The clinical utility model showed that 82% and 88% of liver
      biopsies could be potentially avoided for the diagnosis of severe fibrosis using
      ELF and the combined panel, respectively. The ELF panel has good diagnostic
      accuracy in an independent validation cohort of patients with NAFLD. The addition
      of established simple markers augments the diagnostic performance across
      different stages of fibrosis, which will potentially allow superior
      stratification of patients with NAFLD for emerging therapeutic strategies.

PMID- 18038453
TI  - Diameter of vessels across the tonsillar capsule as an anatomical consideration
      for tonsillectomy.
AB  - The authors measured the diameters of vessels around the surgical plane of
      tonsillectomy to investigate an anatomical basis to reduce hemorrhage. Thirty
      tonsils removed from 15 adult cadavers with the mean age of 56 years (range 44-71
      years) at the time of death were studied. Calibration of the vessels across the
      tonsillar capsule was performed at the 1-mm intracapsular, capsular, and 1-mm
      extracapsular plane as artery and vein, respectively. The average diameter of the
      arteries was 73.0 +/- 33.1 mum at the 1-mm intracapsular plane, 94.7 +/- 33.5 mum
      at the capsular plane, and 139.5 +/- 51.2 mum at the 1-mm extracapsular plane.
      For the veins, it was 62.9 +/- 38.7 mum at the 1-mm intracapsular plane, 86.8 +/-
      50.4 mum at the capsular plane, and 133.6 +/- 78.6 mum at the 1-mm extracapsular
      plane. The diameters of the vessels at the 1-mm intracapsular plane were
      significantly smaller than those at the capsular plane (P < 0.01), and likewise
      the diameters of the vessels at the capsular plane were significantly smaller
      than those at the 1-mm extracapsular plane (P < 0.01). The result of this study
      on the diameter of the vessels across the tonsillar capsule could be considered
      to be an important factor providing an anatomical rationale for a change in
      recommendation leading to safer tonsillectomies that minimize vascular injury.

PMID- 18038454
TI  - Unique muscle in the hypothenar region.

PMID- 18038455
TI  - An unusual articulation at the lumbosacral junction.

PMID- 18038456
TI  - Neurotransmitter diseases and related conditions.

PMID- 18038457
TI  - Concentration effect of Riesling Icewine juice on yeast performance and wine
      acidity.
AB  - AIMS: The objective of this study was to determine the effect of increasing juice
      soluble solids above 40 degrees Brix on wine yeast's ability to grow and ferment
      the juice, with particular focus on acetic acid production, titratable acidity
      (TA) changes and the maximum amount of sugar consumed by the yeast. METHODS AND
      RESULTS: Riesling Icewine juices at 40, 42, 44 and 46 degrees Brix were
      inoculated with K1- V116 at 0.5 g 1(-1) and fermented at 17 degrees C until sugar
      consumption ceased. Increasing soluble solids showed strong negative linear
      correlations with yeast growth, sugar consumption and ethanol production (r = 
      0.999, -0.997 and 0.984, P < 0.001, respectively). Acetic acid, glycerol and TA
      production normalized to sugar consumed showed strong positive correlations to
      the initial juice concentration (r = 0.992, 0.963, and 0.937, P < 0.001
      respectively) but no correlation was found for ethanol production. The acetic
      acid produced as a function of sugar consumed was positively correlated to the
      glycerol produced (r = 0.970, P < 0.001). The final TA of the wines ranged
      between 11.8 and 13.7 g 1(-1) tartaric acid, increasing by 2.3-3 g 1(-1) over the
      starting juice. The increase in TA was positively correlated to the increase in
      acetic acid produced after normalizing the data to the amount of sugar consumed
      (r =0.975, P < 0.001). The acid equivalents resulting from the increase in acetic
      acid accounted for 80-100% of the TA increase when converted to units of tartaric
      acid. In the final Icewines, acetic acid represented 19-20% of wine TA.
      CONCLUSIONS: Increasing Icewine juice concentration from 40 to 46 degrees Brix
      increases the proportion of yeast sugar metabolism towards glycerol and acetic
      acid production to cope with the increased osmotic stress by decreasing yeast
      growth, sugar consumption rate, the total amount of sugar consumed and the total
      amount of ethanol produced. The high proportional contribution of acetic acid to
      titratable acidity in Riesling Icewine may affect acidity perception.
      SIGNIFICANCE AND IMPACT OF THE STUDY: We have determined that 10% v/v ethanol
      would not be achievable with initial juice concentrations above 42 degrees Brix
      and that Riesling Icewine juice above 52.5 degrees Brix would be theoretically
      unfermentable. The high proportional contribution of acetic acid to TA may be an
      important factor in the organoleptic balance of these Icewines.

PMID- 18038458
TI  - Guidelines needed for medical use of marijuana.

PMID- 18038459
TI  - Policy drives harm reduction for drug abuse and HIV/AIDS prevention in some
      developing countries.

PMID- 18038460
TI  - Advances in neurobiological research related to interventions in adolescents with
      substance use disorders: research to practice.

PMID- 18038461
TI  - Genomewide study of multiple sclerosis.

PMID- 18038462
TI  - Genomewide study of multiple sclerosis.

PMID- 18038463
TI  - Acute ischemic stroke.

PMID- 18038465
TI  - HIV prevention in China gets cash boost.

PMID- 18038464
TI  - Normotensive ischemic acute renal failure.

PMID- 18038466
TI  - Current awareness in geriatric psychiatry.

PMID- 18038467
TI  - [Long-term clinical efficiency of endovascular treatment using Cypher rapamycin
      eluting stents in patients with coronary heart disease].
AB  - The study was undertaken to analyze the long-term results in patients with
      coronary heart disease (CHD) one year or more after Cypher stent implantation. It
      covered 1221 patients. One-, two-, and three- vessel lesions were observed in 693
      (56.8%), 344 (28.2%), and 184 (15%) patients, respectively. A total of 1967
      Cypher stents were implanted. The results of treatment were analyzed 1 and 2
      years after intervention. The efficiency of a procedure was evaluated by the
      following parameters: the presence or absence of anginal symptoms, the presence
      and absence of complications (fatal outcome, myocardial infarction). The
      following morphological parameters: the rate of restenosis and that of late stent
      thrombosis were also assessed. The results of one- and two-year follow-ups were
      used to make a multivariate analysis of the clinical and morphological predictors
      of coronary complications (fatal outcome, myocardial infarction, recurrent angina
      pectoris) in the late period, as well as the predictors of restenosis and late
      stent thrombosis. Restenosis following 1 year of Cypher stent implantation is
      3.1%. The factors that significantly increase the risk of this complication
      within the first year are diabetes mellitus and revascularization in the patients
      operated on. The one-year rate of Cypher stent thromboses is 1.6%. Patients'
      discontinuation of antiaggregant therapy is the sole factor that significantly
      increases the rate of their late thromboses in this period. Within the second
      year of a follow-up, the rate of late Cypher stent thromboses is 1.8%. The risk
      of this complication is significantly increased by factors, such as a lengthy
      (more than 3 mm) stented portion, renal failure, and less than 40% left
      ventricular ejection fraction.

PMID- 18038468
TI  - [Radionuclide technique for diagnosing the mononuclear phagocytic system].
AB  - The purpose of the investigation was to determine the possibility of using
      colloidal radiopharmaceuticals to study the mononuclear phagocytic system in the
      clinical setting. The technique for studying the mononuclear phagocytic system
      using the labeled compounds involved the single intravenous administration of a
      radiolabeled colloidal solution, the registration and plotting of a change in
      colloid radioactivity, and the determination of radioactivity of the body as a
      whole and that of the lung, liver, spleen, and peritoneum. The performed
      investigation using colloidal radiopharmaceuticals makes it possible to study the
      mononuclear phagocytic system and to reveal the regularities of colloid
      accumulation in the organs and tissues in various diseases just in the clinical
      setting.

PMID- 18038469
TI  - Simply a pimple, or is it worse?

PMID- 18038470
TI  - Picture this. Looking at the diabetic brain.

PMID- 18038472
TI  - The wisdom of robins. Cultivating the "grown and flown" patient.

PMID- 18038471
TI  - The secret life of Zs. A good night's sleep can help you lose weight.

PMID- 18038473
TI  - Healthy eating. Fall colors, big flavor. The season's produce is tasty and
      nutritious.

PMID- 18038474
TI  - Women & diabetes. 6 health issues you can't ignore.

PMID- 18038475
TI  - Idol time. Pop star Elliott Yamin talks about life with diabetes.

PMID- 18038476
TI  - The inflammation factor. Scientists are looking at a potential new culprit in the
      development of heart disease and type 2 diabetes.

PMID- 18038477
TI  - Research profile. New mom, new lifestyle. Preventing type 2 diabetes after
      childbirth. Wanda Kay Nicholson, MD, MPH, MBA.

PMID- 18038478
TI  - New worries over lead: our latest tests find the toxic metal in more products.

PMID- 18038479
TI  - Air purifiers: filtering the claims.

PMID- 18038480
TI  - Medical devices: problems on the rise.

PMID- 18038481
TI  - Numbers.

PMID- 18038482
TI  - [Community health nurses, a new convention and employment mode. Interview by
      Serge Benaderette].

PMID- 18038483
TI  - Medicare program; delay of the date of applicability for certain provisions of
      Physicians' Referrals to Health Care Entities With Which They Have Financial
      Relationships (Phase III). Final rule.
AB  - This final rule delays the date of applicability of certain specified
      compensation arrangements only, until December 4, 2008.

PMID- 18038484
TI  - [Education of health staff and research].

PMID- 18038485
TI  - TRICARE; expansion of geographic scope of the TRICARE Retiree Dental Program.
      Final rule.
AB  - This final rule expands the geographic scope of the TRICARE Retiree Dental
      Program (TRDP) to overseas locations not currently covered by the program. At
      this time, TRDP is applicable only in the 50 United States (U.S.) and the
      District of Columbia, Canada, Puerto Rico, Guam, American Samoa, the Commonwealth
      of the Northern Mariana Islands, and the U.S. Virgin Islands. Expanding the
      geographic scope of the program will ensure that all TRICARE-eligible retirees
      are eligible for the same dental benefits, regardless of their location. There
      are no additional Government costs associated with this final expansion of TRDP
      overseas as TRDP costs are borne entirely by enrollees through premium payments.

PMID- 18038486
TI  - Issuance of multiple prescriptions for schedule II controlled substances. Final
      rule.
AB  - The Drug Enforcement Administration (DEA) is finalizing a Notice of Proposed
      Rulemaking published on September 6, 2006 (71 FR 52724). In that document, DEA
      proposed to amend its regulations to allow practitioners to provide individual
      patients with multiple prescriptions, to be filled sequentially, for the same
      schedule II controlled substance, with such multiple prescriptions having the
      combined effect of allowing a patient to receive over time up to a 90-day supply
      of that controlled substance.

PMID- 18038487
TI  - [The edification of a poetic tomb: from ritual to anthology].

PMID- 18038488
TI  - ["A recollection": the arrangement of Ambroise Pare's Oeuvres].

PMID- 18038489
TI  - [The Epistres morales et familieres (1545) by Jean Bouchet: from medieval
      hierarchy to humanist dialogue].

PMID- 18038490
TI  - [Priority objective, the management of knowledges coming from nursing research].

PMID- 18038491
TI  - Nurses in Nazi Germany.

PMID- 18038493
TI  - The aesthetic.

PMID- 18038492
TI  - [Chemical warfare and the Palestine campaign in World War I].

PMID- 18038494
TI  - Botanical ingredients in cosmeceuticals.
AB  - During the last 10 to 15 years, complementary and alternative medicine (CAM) has
      become increasingly popular in the US. Within this realm of health care, oral and
      topical herbal supplements have become some of the most frequently used
      alternative therapies. Most herbal supplements are based on, or include, several
      botanical ingredients with long histories of traditional or folk medicine usage.
      Among the numerous botanical ingredients available on the market today, several
      are believed to confer dermatologic benefits. This article will focus on a select
      group of botanical compounds, many of which have long traditions in Asian
      medicine, with potential or exhibited dermatologic applications, including
      curcumin, Ginkgo biloba, ginseng, silymarin, soy, and tea tree oil. Other
      botanical agents, such as arnica, bromelain, chamomile, pomegranate, caffeine,
      green tea, licorice, and resveratrol, are also briefly considered. Some of these
      ingredients have been incorporated into topical formulations.

PMID- 18038495
TI  - Juvederm: a hyaluronic acid dermal filler.
AB  - Over the past decade, the use of nonsurgical products and devices to correct
      facial contour defects and signs of skin aging has exploded with new lasers,
      toxins for muscle relaxation, and dermal fillers revolutionizing aesthetic
      medicine. Of all the nonsurgical modalities employed during this period, the
      dermal filler industry has seen the most growth in demand. In 2006, the worldwide
      market for dermal fillers increased by 19%; and the US market is expected to
      increase a further 20% to 25%. This is due in large part to new products,
      particularly the hyaluronic acids such as Juvederm, which now promise greater
      longevity, fewer side effects, a more natural appearance, and easier
      administration.

PMID- 18038496
TI  - Nonablative skin tightening with a variable depth heating 1310-nm wavelength
      laser in combination with surface cooling.
AB  - A near-infrared laser with the ability to target different depths within skin has
      been developed and evaluated for the application of facial and neck skin
      tightening in a pilot clinical study. The device consists of a combination of a
      1310-nm wavelength and sapphire contact cooling. Cooling temperature and laser
      pulse duration were varied to target different dermal depths in various subgroups
      of the subject population. Quantitative changes in various categories
      characterizing the aging skin employing a comprehensive grading scale as well as
      subject satisfaction were calculated. A mean improvement of 7.9% (95% CI
      [confidence interval] 3.6-12.3) in laxity and 10.6% (95% CI 5.8-15.4) in rhytides
      was determined by quantitative grading at one month after the treatment regimen.
      These values were 11.0% (5.5-16.5) and 11.7% (5.8-17.7) at 3 months after the
      treatment regimen. The percent of patients reporting mild or better improvement
      in laxity of the face and neck was 78% and 61% at one month, and 63% and 61% at 3
      months, respectively. The discomfort was minimal. Side effects were limited to
      short-term erythema and edema. In summary, a variable depth heating laser can
      achieve skin tightening and wrinkle reduction with high subject satisfaction.

PMID- 18038497
TI  - Use of topical lidocaine for cosmetic dermatologic procedures.
AB  - Topical anesthetic agents are frequently used by dermatologists to decrease the
      pain associated with a variety of cutaneous procedures, including laser surgery,
      soft tissue augmentation, and other cosmetic surgical treatments. These lidocaine
      containing creams play an integral role in the cosmetic dermatology office by
      providing patient comfort with minimal side effects. This review of topical
      lidocaine preparations should aid practitioners in the selection of an
      appropriate topical anesthetic, taking into consideration its onset and duration
      of action and potential side effects.

PMID- 18038498
TI  - Plasma skin regeneration technology.
AB  - Plasma skin regeneration is a novel type of skin rejuvenation technology
      developed over the last 3 years. Plasma is the fourth state of matter in which
      electrons are stripped from atoms to form an ionized gas. Although high
      temperature plasmas have been used in surgery for over a decade, plasma had
      previously been used as a conduction medium for electric current. Unlike lasers
      which rely on the principle of selective photothermolysis to deliver heat to
      specific targets in the skin, plasma technology delivers heat energy directly to
      tissue upon contact without reliance on skin chromophores. The plasma itself
      produces controlled thermal damage to the skin surface to elicit changes such as
      new collagen formation and improvement in photodamaged skin. The technology can
      be used at varying energies for different depths of effect, from superficial
      epidermal effects to deeper dermal heating.

PMID- 18038499
TI  - Treatment of photoaging with a very superficial Er:YAG laser in combination with
      a broadband light source.
AB  - BACKGROUND AND OBJECTIVE: Studies documenting improvement following combined
      laser and light-based devices are needed. The objective of this study was to
      evaluate clinical, histological, and ultrastructural changes in photodamaged
      facial skin following sequential treatment with ablative superficial erbium:YAG
      (Er:YAG) laser peels and nonablative intense pulsed light, or broadband light
      (BBL), treatments. STUDY DESIGN/MATERIALS AND METHODS: Fifteen subjects with
      photodamaged facial skin and Fitzpatrick skin types I to III underwent 3 monthly
      treatments with the Profile system (Sciton, Inc, Palo Alto, CA) utilizing very
      superficial MicroLaserPeel settings of 2.5 to 5.0 J/cm2 and BBL settings of 515-,
      560-, or 590-nm filters, 10-msec pulse duration, and fluences of 12 J/cm2. Five
      subjects underwent pre- and post-treatment postauricular skin biopsies for
      evaluation of treatment-induced light and electron microscopic changes. RESULTS:
      Twelve subjects completed the study. Both blinded evaluator and subject
      assessment of clinical changes documented significant improvement in photodamaged
      skin, with the greatest improvement achieved in overall appearance and epidermal
      dyspigmentation. These results were largely maintained at 3 months following the
      last treatment. Light microscopy showed changes in the epidermis, collagen, and
      elastic fibers consistent with a wound repair mechanism to the depth of 250 to
      350 microns. Electron microscopy revealed a slight decrease in the average
      collagen fiber thickness, pointing to an increase in type III collagen.
      CONCLUSION: A protocol utilizing multiple combined superficial Er:YAG ablative
      treatments and nonablative BBL treatments lead to a significant improvement in
      the clinical signs of photodamaged skin, with histological and ultrastructural
      evidence of new collagen formation.

PMID- 18038500
TI  - Fractionated delivery systems for difficult to treat clinical applications: acne
      scarring, melasma, atrophic scarring, striae distensae, and deep rhytides.
AB  - Fractional resurfacing or laser therapy (FLT) represents a technology that seeks
      to address the limitations of both ablative resurfacing and nonablative
      treatments. Many companies now offer versions of fractionated erbium or carbon
      dioxide lasers. The purpose of this paper is to examine FLT for difficult to
      treat applications such as melasma, acne scarring, atrophic scarring, striae
      distensae, and deep rhytides. Fractional laser therapy is a truly novel approach
      to many conditions, especially those with dermal pathology. Although published
      peer review data is limited, the ability to effectively and safely treat these
      conditions in all skin types appears to have been significantly enhanced with
      this new modality. We are early in our scientific explorations of what is
      possible with FLT.

PMID- 18038503
TI  - Botulinum toxin type A enhances the outcome of fractional resurfacing of the
      cheek.
AB  - Fractional resurfacing and fractionally ablative (CO2) resurfacing have become
      increasingly popular in recent years. They hold the promise of delivering skin
      rejuvenation with fewer risks and less downtime than traditional ablative
      resurfacing. Despite the popularity of the procedures and the trend toward
      synergistic activity in aesthetic dermatology, there is little documentation
      regarding the use of botulinum toxins and fractional resurfacing for the midface.
      This report discusses the use of botulinum toxin type A and fractional
      resurfacing for the cheek area. Although it is a limited, single case report, it
      provides insight into the potential for this combination and may serve as a
      stimulus for a large, well-controlled study to evaluate the use of toxins in this
      and similar areas.

PMID- 18038501
TI  - Photodynamic therapy update 2007.
AB  - The use of photodynamic therapy (PDT) in the US has shown record growth in 2007
      with more clinicians utilizing PDT for more clinical entities than ever before.
      Research endeavors utilizing PDT in published clinical manuscripts have been slow
      in 2007 and yet the use continues to rise significantly. This manuscript will
      highlight the state of PDT in the US as 2007 comes to a close and focus on the
      future of PDT as we move toward 2008.

PMID- 18038502
TI  - Evaluating the efficacy in improving facial photodamage with a mixture of topical
      antioxidants.
AB  - This study evaluates the efficacy and tolerability of an investigational study
      cream composed of 3 ingredients (green and white teas, mangosteen, and
      pomegranate extract), Vitaphenol Skin Cream (La Jolla Spa MD, La Jolla CA), as
      compared to a placebo cream in rejuvenating facial skin. Twenty healthy females
      between the ages of 35 and 65 with demonstrable facial wrinkling, achieving a Rao
      Goldman wrinkle scale score of 2 or above, applied either Vitaphenol Skin Cream
      or placebo cream to a randomized half of their face twice daily for 60 days and
      returned for follow-up after 2 weeks. Twice as many subjects indicated an
      enhancement of skin texture (eg, reduction in pore size, roughness, and touch)
      with the usage of Vitaphenol versus placebo. In all, 41% of the study subjects
      preferred the half of their face that had been receiving Vitaphenol, while only
      0.06% of the subjects favored the placebo side. PRIMOS images from periorbital
      skin treated with Vitaphenol demonstrated an average improvement in skin
      smoothness of 1 mm3, whereas skin treated with placebo showed an average decrease
      in smoothness or an increase in skin roughness of 0.9 mm3. The addition of 3
      antioxidants, green and white teas, mangosteen, and pomegranate, have an additive
      effect to enhance the improvement of age-related changes in the skin.

PMID- 18038504
TI  - Nanotechnology.

PMID- 18038506
TI  - Strength in numbers: the power of > one.

PMID- 18038507
TI  - As I see it.

PMID- 18038508
TI  - Organizing for change.

PMID- 18038509
TI  - The right to organize.

PMID- 18038510
TI  - Diabetic muscle infarction: a poorly understood, rare complication of long
      standing diabetes mellitus.
AB  - Diabetic muscle infarction (DMI) is a rare complication of long-standing
      diabetes. It does have a fairly characteristic clinical presentation and
      appearance on magnetic resonance imaging. Despite several hypotheses, the
      etiology of DMI has not been convincingly determined. A patient with DMI is
      presented in this report. Analysis of his muscle biopsy suggests impaired nitric
      oxide formation. We postulate that because nitric oxide is protective against
      ischemia and/or reperfusion injury in cardiac muscle, insufficient production in
      skeletal muscle could also predispose to the development of DMI.

PMID- 18038511
TI  - Access barriers to dental care for Medicaid patients.
AB  - OBJECTIVE: Indigent children have higher incidence of dental caries.
      Recommendations are for preventive dental visits yearly, starting at age one
      year. In spite of Medicaid coverage of such visits, utilization remains low. Our
      interest was in understanding the reason for underutilization of dental services.
      We hypothesized that such underutilization results from inadequate knowledge of
      available coverage or of the need for early care. METHODS: Parents of 77 four
      year-olds were surveyed at a university-affiliated pediatric clinic with dental
      services on site. Parents were asked about their knowledge of Medicaid dental
      coverage, of the need for early dental care, and frequency of care their child
      received. Medical records since birth were reviewed. RESULTS: All parents were
      aware of the Medicaid eligibility for services; 80% knew dental care was needed
      by age one year. Only 69% of the children in the survey had received dental care
      at our clinic; among the remaining 31%, one third reported never receiving dental
      care, and two thirds stated that they received dental care elsewhere. Among those
      receiving care in our clinic, 37% had initial visits between 12-23 months old.
      Annual dental visits for one through four years old were made by 15% of the
      children, while 25% were seen just once in the four-year interval. CONCLUSION:
      Parents were aware of the availability and necessity of dental care in early
      childhood, yet few of their children received the recommended prophylactic
      visits. Medical care providers caring for children play an important role as
      advocates of early and regular prophylactic dental visits.

PMID- 18038512
TI  - Tobacco cessation treatment knowledge, attitudes and practices of Kentucky
      physicians.
AB  - Kentucky continues to report the highest adult smoking rates in the nation, and
      this persistent public health problem leads to substantial morbidity, mortality,
      and economic costs for the state. Given that physician intervention has been
      shown to increase cessation rates, the Kentucky Cancer Program developed a self
      study continuing education program for physicians to promote the implementation
      of effective tobacco cessation treatment strategies. As a preliminary component,
      a pre-program survey was administered to participants to measure current
      knowledge, attitudes, and practices regarding the treatment of tobacco use and
      dependence. Results from this survey offered an opportunity to describe and
      analyze the areas in which physicians were utilizing tobacco cessation treatment
      approaches consistent with clinical practice guidelines as well as areas in which
      further training and resources were needed to improve clinical tobacco cessation
      treatment practices. Overall, physicians accepted their primary role in tobacco
      cessation treatment and acknowledged a moderate level of comfort with this role.
      They also reported implementing several of the recommended "5 A's" from the
      Treating Tobacco Use and Dependence: Clinical Practice Guideline. Further
      examination of the data, however, revealed that knowledge, attitudes, and
      practices were weaker regarding specific, formal, and systematic implementation
      of tobacco cessation treatment. Effective training and resources would provide
      physicians with the tools necessary to intervene with tobacco users more
      consistently and to reduce the health and economic burden of tobacco use and
      dependence in Kentucky.

PMID- 18038513
TI  - To err is human, communication is divine.

PMID- 18038514
TI  - The National Cancer Institute's Cancer Information Service: an untapped resource
      for Kentucky health professionals.

PMID- 18038515
TI  - Intravascular device management--an update.

PMID- 18038516
TI  - Nurse practitioner roles--an exercise in professionalism, safety and quality.

PMID- 18038517
TI  - Intensive care nurses' perceptions of brain death.
AB  - Research during the last 2 decades has revealed significant confusion or lack of
      acceptance and inconsistent application of the brain death concept within the
      medical and nursing professions. The aim of this naturalistic and descriptive
      study was to investigate the extent to which a sample of 40 Australian intensive
      care nurses regarded brain death as a meaningful conception of death. In contrast
      with the majority of the literature pertaining to health care professionals'
      perceptions of brain death which has focused upon clinical knowledge, the study
      elicited the expression of personal beliefs. The study utilised a structured
      interview method with nurses from seven metropolitan intensive care units (ICUs).
      Transcript analysis revealed five categories of perception constituting a
      spectrum ranging from complete acceptance to complete rejection, with almost half
      (48%, n = 19) the sample regarding the brain dead patient as less than completely
      meaningfully dead. Rather than supporting the literature's suggestion that non
      acceptance of the medico-legally recognised brain death notion is, necessarily,
      evidence of professional ignorance, the findings suggest the participants holding
      these perceptions were generally well-informed about brain stem function and
      brain death diagnosis. The study affirms the importance of supportive workplace
      environments which facilitate the expression of dissonant perceptions and
      proposes that educators and managers must acknowledge these dissonances.

PMID- 18038519
TI  - Check x-ray quiz. Classical posterior rib notching that occurs with coarctation
      of the aorta.

PMID- 18038518
TI  - Registered nurses' self-perceived level of competence following completion of a
      specialist graduate certificate.
AB  - Utilising the Competency Standards for Specialist Critical Care Nurses (CSSCCN)
      as a framework, this study sought to examine the perceived level of competence
      (PLC) of the graduates of a Graduate Certificate in Intensive Care Nursing
      (GCICN) and the level at which the GCICN influenced the graduates' PLC. A rating
      scale of 1-5 and an open-ended questionnaire were utilised. The graduates' mean
      PLC in the competency 'engaging in research' was rated as the lowest and
      'recognising own abilities and professional competence' as the highest. Graduates
      of 1991-1994 rated their PLC on all the competencies lower in comparison to
      graduates of 1995-1997. Graduates' PLC on enabling and clinical problem solving
      domains were rated better than the reflective and leadership domains. A
      significant correlation was demonstrated between the graduates' PLC and their
      perceptions as to the course's influence on their PLC.

PMID- 18038521
TI  - Opportunities to grow on research successes.

PMID- 18038520
TI  - Long-term risk factor control after a cardiac rehabilitation programme.
AB  - This study examined the hypothesis that Phase II cardiac rehabilitation
      participants (CRP) had better long-term risk factor control, self-rated
      perception of health and return to work rates than non-participants (NP) between
      18 and 36 months post myocardial infarction (MI). It was a comparative study in a
      550 bed hospital. Approximately half of both groups did not achieve a total
      cholesterol (TC) of 5.5 mmol/L or less. Compared with NP, CRP were significantly
      more likely to have a TC < = 6.5 mmol/L (7% vs. 28%) (p = 0.006). NP with TC >
      6.5 mmol/L were significantly less likely to be on treatment (p = 0.002). CRP
      were more likely to regularly exercise than NP (79% vs. 61%) (p = 0.038). The
      success rate for blood pressure targets, return to work rates and self-rated
      perception of health were similar in both groups. In conclusion, CRP had better
      long-term control of some risk factors than NP. The study provides comparative
      longer-term patient outcomes after an Australian cardiac rehabilitation (CR)
      programme and forms the basis for further outcome measurement.

PMID- 18038522
TI  - The development of a nurse practitioner.

PMID- 18038523
TI  - Research priorities for Australian critical care nurses: do we need them?
AB  - The development of research priorities for critical care nurses has been
      previously examined from the perspective of both Australian and international
      critical care nursing experts. A variety of techniques have been used to
      determine research priorities for critical care nursing, however, a clear
      articulation of research priorities for Australian critical care nurses, which
      are both timely and encompass all aspects of critical care nursing practice, is
      lacking. Research priorities previously determined in Australia and elsewhere
      identify similar clinical research priorities such as nutritional support,
      infection control, supporting respiratory and cardiac function, and follow-up of
      critically ill patients. However, differences between the few available studies
      exist, possibly because of the changing nature of critical care nursing practice.
      Despite the identification of research priorities for critical care nursing in
      the past, there is little evidence to demonstrate a direct effect on research
      output in these areas. Future development of research priorities for Australian
      critical care nurses needs to be carefully considered. It is essential that
      identification of such research priorities be done within the context of their
      intended use.

PMID- 18038524
TI  - Staff perceptions on the use of a sedation protocol in the intensive care
      setting.
AB  - Sedation protocols are increasingly being investigated as a method of achieving
      improved patient outcomes whilst guiding the decision making of both nursing and
      medical practitioners. However, only a limited number of studies have
      investigated the perceptions of staff towards a sedation protocol during its
      implementation. This study was designed to survey the perceptions of staff
      regarding the implementation of a sedation protocol in an Australian intensive
      care unit (ICU). Questionnaires were distributed to all multidisciplinary team
      members who had used the sedation protocol. The response rate was 50% (n=70). The
      questionnaire combined the use of visual analogue scales plus a comments section
      to obtain qualitative data. The results revealed that staff perceived sedation
      management to be enhanced with the use of a protocol and therefore should be
      incorporated into routine clinical practice. Staff perceived that providing clear
      guidelines that facilitated decision making and assisted beginner practitioners
      enhanced sedation management. In addition, there was a perceived improvement in
      the patient outcomes, including a decrease in the frequency of over-sedation
      resulting in a reduced ICU stay. Positive perceptions may assist in the
      introduction of other interventional protocols. Other protocols may target areas
      where variability in clinical decision making exists, despite research evidence
      that supports specific therapeutic interventions. Further studies addressing
      protocol implementation for clinical interventions are warranted in other ICU
      settings.

PMID- 18038525
TI  - Post discharge problems in women recovering from coronary artery bypass graft
      surgery.
AB  - This study was conducted to describe the types and frequency of problems
      Australian women experience when recovering at home in the first 6 weeks
      following coronary artery bypass graft (CABG) surgery and the relationship
      between symptom experience and psychological distress. A convenience sample of 52
      women (mean age 66.31 years, range 53-79 years) who had uncomplicated CABG
      surgery was selected from two tertiary hospitals in Sydney. A descriptive design
      was used with information related to post-operative problems collected by
      telephone interview at 1, 3 and 6 weeks post discharge using a semistructured
      questionnaire. Psychological distress was assessed at 12 weeks post discharge
      using the Hospital Anxiety and Depression Scale (HADS). Responses were
      categorised, collapsed and described using frequencies and percentages.
      Relationships were assessed by Spearman's r. The most common problems in the
      first and third weeks post discharge were sleeplessness and nausea or poor
      appetite and chest incision pain. Although problems improved over the first 6
      weeks post-operatively, approximately one-quarter of the women still reported
      chest incision pain and almost 40% reported problems with leg wounds and oedema.
      The number of problems experienced at 6 weeks was significantly correlated with
      depression at 12 weeks. These findings support the importance of a preoperative
      education programme that includes anticipation of physical problems in the
      immediate post-operative period and a follow-up of female patients in the early
      transition period following hospital discharge.

PMID- 18038526
TI  - Cardiopulmonary resuscitation guidelines: what next?

PMID- 18038527
TI  - Using 'soft solutions' to meet today's hard challenges in critical care.

PMID- 18038528
TI  - Chest x-ray quiz. Atelectasis of the right upper lobe.

PMID- 18038529
TI  - Multicentre study of delirium in ICU patients using a simple screening tool.
AB  - Traditionally, intensive care unit (ICU) delirium was viewed as benign and was
      under-diagnosed in the absence of ICU-appropriate screening tools. Research
      suggests that up to half of all ICU patients experiencing delirium will continue
      to do so after discharge to the ward, and half of those experiencing delirium in
      the ward will die within 1 year of delirium diagnosis. ICU-specific screening
      tools are now available. The purpose of this study was to identify the incidence
      of delirium in ICU and explore its associations to clinical factors and outcomes.
      A secondary aim was to evaluate the usefulness of the intensive care delirium
      screening checklist (ICDSC). A total of 185 patients in six ICUs in Australia and
      New Zealand were screened for delirium using the ICDSC over two 12-hour periods
      per day for the duration of their ICU admission. Some 84 patients (45%) developed
      delirium. Development of delirium was associated with increased severity of
      illness (acute physiology and chronic health evaluation--APACHE II--and
      sequential organ failure assessment--SOFA), ICU length of stay (LOS), and use of
      psycho-active drugs. Delirious patients showed no statistically significant
      difference in ICU and hospital mortality rates, nor prolonged hospital LOS. The
      ICDSC was found to be user-friendly. The incidence of delirium, observed
      characteristics and outcomes for patients admitted to Australian and New Zealand
      ICUs for > 36 hours without any history of altered mental state fell in the mid
      range and were generally consistent with previous literature. An ICU-specific
      delirium assessment, such as the ICDSC, should be included in routine ICU
      observations to minimise under-diagnosis of this serious phenomenon.

PMID- 18038530
TI  - Life beyond severe traumatic injury: an integrative review of the literature.
AB  - It is only recently that recognition of the serious and debilitating sequelae of
      trauma has prompted exploration of outcomes beyond survival, such as disability,
      health status and quality of life. This paper aims to review the literature
      describing outcomes following severe traumatic injury to provide clinicians with
      a greater understanding of the recovery trajectory following severe trauma and
      highlight the issues faced by those recovering from such injury. Electronic
      databases, published reference lists and the Internet were searched to identify
      relevant literature. The heterogeneous nature of published literature in this
      area prohibited a systematic approach to inclusion of papers in this review.
      Trauma survivors report significant sequelae that influence functional status,
      psychological wellbeing, quality of life and return to productivity following
      severe injury. Key themes that emerge from the review include: current trauma
      systems which provide inadequate support along the recovery trajectory;
      rehabilitation referral which is affected by geographical location and provider
      preferences; a long-term loss of productivity in both society and the workplace;
      a high incidence of psychological sequelae; a link between poor recovery and
      increased drug and alcohol consumption; and valued social support which can
      augment recovery. Future research to evaluate interventions which target the
      recovery needs of the severely injured patients is recommended. Particular
      emphasis is required to develop systematic, sustainable and cost-effective follow
      up to augment the successes of existing acute trauma services in providing high
      quality acute resuscitation and definitive trauma management.

PMID- 18038531
TI  - A phenomenological study of medically induced unconsciousness in intensive care.
AB  - Critically ill patients who require mechanical ventilation in intensive care
      units (ICUs) are usually sedated with drugs such as Morphine and Midazolam in
      order to facilitate ventilation, relieve pain and lower metabolic demands.
      Participants in this research were sedated to the point of 'medically induced
      unconsciousness' in that they were non eye opening nor responsive to verbal
      directives. A purposive sample of five individuals who had experienced the
      phenomenon of 'medically induced unconsciousness' were interviewed indepth. These
      interviews were transcribed verbatim and then analysed using a Husserlian
      phenomenological approach. Three essences were revealed within the data, each
      with associated themes. These essences were utter helplessness, cognition and
      succour. Utter helplessness was linked to: an inability to communicate either
      verbally or physically; pain during procedures; a sense of threat to personal
      safety; depersonalisation; loss of control and a sense of loneliness. Rather than
      an alteration of cognition, the themes that emerged within this second essence
      revealed attempts by participants to understand the experiences associated with
      'medically induced unconsciousness'. These themes were: dreams; dissociation of
      self from the physical body; time-space relatedness and chaos. The final essence
      to emerge was that of succour. This essence portrays some of the more positive
      aspects of the experience. The themes revealed were: security in the ventilator;
      comfort in voices; human presence; painfree and purpose. Participants in this
      study were experiencing many things as they lay unresponsive on their beds in the
      ICU. The absence of physical responses should not be misinterpreted to mean that
      cognitive processes are not occurring. Participants appeared to be attempting to
      make sense of their immediate environment through their dreams.

PMID- 18038532
TI  - Who's best practice is it anyway?

PMID- 18038533
TI  - Assessing clinical practice using the ACCCN Competency Standards: a valid tool?

PMID- 18038534
TI  - Transfer out of intensive care: a qualitative exploration of patient and family
      perceptions.
AB  - OBJECTIVE: To examine perceptions of ICU transfer held by patients and their
      family members, focusing specifically on those aspects of transfer perceived as
      difficult and those perceived as helpful. DESIGN: Descriptive qualitative case
      study design. SETTING: General ICU of a large regional Australian teaching
      hospital. PATIENTS: A total of 7 patients and 6 family members were purposefully
      recruited at one-month post-discharge from hospital. Participants were selected
      for their ability to recall ICU transfer, the involvement of family members and
      their ability to articulate their experiences. MAIN OUTCOME MEASURES: Two focus
      groups (one for patients and one for families) were conducted in the hospital
      setting, aimed at capturing the individual and collective perceptions of transfer
      out of intensive care. RESULTS: Four themes emerged from the data that reflected
      the complex and emotional nature of transfer out of intensive care. These themes
      included (1) a sense of sudden abandonment (2) pervasive feelings of
      vulnerability and helplessness, (3) a loss of importance and (4) ambivalence
      about the experience. CONCLUSIONS: The need for ICU nurses, ward nurses and
      affiliated healthcare professionals to provide emotional support throughout ICU
      transfer is the most significant implication of the study. Strategies to provide
      this support must be developed, implemented and evaluated.

PMID- 18038535
TI  - Dealing with death: an audit of family bereavement programs in Australian
      intensive care units.
AB  - Patient death in Intensive Care Units (ICU) can be sudden and unexpected, leading
      to emotionally charged situations and life changing circumstances for family
      members. Supporting families during and after this critical period is
      particularly challenging for ICU nurses who often feel dissatisfied with the way
      they deal with the situation. Bereavement programs in various areas of nursing
      have been reported to be beneficial in promoting normal grief patterns. There is,
      however, a lack of research in the area of evaluation of bereavement programs in
      adult ICUs. This paper presents the results of an Australia-wide audit on current
      practices in the area of bereavement programs within adult ICUs. Surveys were
      sent to 117 adult Australian ICUs; 99 surveys were returned completed (84.6%
      response rate). It was identified that most surveyed units offer minimal
      components of bereavement programs, such as viewing of the deceased and
      communicating with family members. Less than one third (n=26) provide additional
      follow-up services in the form of telephone calls and sympathy cards or referral
      to additional services. Ten units employ some form of program evaluation. Verbal
      feedback from staff and families is the primary assessment method. Over half of
      responding ICUs indicated they are considering or interested in providing a
      bereavement program in their unit. This study highlights the need for research
      based data to support the introduction or deletion of strategies for bereavement
      programs using family-centred outcome measures. ICU nurses are interested in this
      area of clinical practice and require considerable support. It is recommended
      that this support can come via postgraduate and on-going education, hospital
      policies and procedures.

PMID- 18038537
TI  - Best practice in stabilisation of oral endotracheal tubes: a systematic review.
AB  - Mechanical ventilation of patients in intensive care units is common practice.
      Artificial airways are utilised to facilitate ventilation and the endotracheal
      tube (ETT) is most commonly used for this purpose. The ETT must be stabilised to
      optimise ventilation and avoid displacement or unplanned extubation. Tube
      movement is a major factor in causing airway trauma. A destabilised tube can
      cause fatal complications. A systematic review was conducted to identify and
      analyse the best available evidence on ETT stabilisation to determine which
      stabilisation method resulted in reduced tube displacement and the least amount
      of unplanned or accidental extubations. The types of stabilisations included one
      or a combination of the following methods: twill or cotton tape, adhesive tape,
      gauze, or a manufactured device. All relevant randomised controlled and quasi
      experimental studies of ETT stabilisation practices, identified through
      electronic and hand searching, were assessed for inclusion in the study. One
      published randomised controlled trial and six published quasi-experimental
      studies met the inclusion and exclusion criteria and were retrieved. Data were
      extracted independently by two reviewers. Results of the systematic review showed
      that no single method of ETT stabilisation could be identified as superior for
      minimising tube displacement and unplanned or accidental extubations. Rigorous
      randomised controlled trials with clearly identified and described ETT
      stabilisation methods are required to establish best practice. In addition,
      comparative research to evaluate cost effectiveness and nursing time requirements
      would also be of significant benefit to critical care nursing practice.

PMID- 18038536
TI  - A survey of sedation assessment and management in Australian and New Zealand
      paediatric intensive care patients requiring prolonged mechanical ventilation.
AB  - INTRODUCTION: A retrospective analysis of sedation management for children
      receiving prolonged ventilation in one Australian paediatric intensive care unit
      (PICU) revealed no identifiable pattern in sedation management and an inadequacy
      in the sedation scoring system. Therefore, the investigators sought to explore
      the current practice of sedation in critically ill children in PICUs across
      Australia and New Zealand. METHOD: This study used a mail-out survey to audit
      sedation management within the eight dedicated Australian and New Zealand PICUs.
      RESULTS: 100% of the units surveyed replied (n=8). There were a total of 6,133
      admissions to 8 Australian and New Zealand PICUs, where 3036 (49.5%) required
      ventilation. Of these children, 888 (29.2%) required ventilation > or =72 hours.
      Only 4 units had written guidelines for sedation management. A combined sedation
      regime of benzodiazepines and opioids was employed in six units. Administration
      and titration of sedation agents was managed by nursing staff alone in six units.
      All units indicated that they aimed to achieve a 'moderate level' of sedation.
      Two units used designated assessment tools for sedation and withdrawal
      assessment. One unit utilised Bispectral Index (BIS) monitoring. CONCLUSION:
      There were similarities observed in the methods and types of sedation agents used
      within Australian and New Zealand PICUs. However, only half of the units had
      guidelines for sedation management, and most units did not use validated
      paediatric scales to assist staff in assessing patient sedation and pain levels.
      Therefore it is recommended that a standardised approach to sedation assessment
      and management of critically ill children requiring prolonged ventilation be
      developed and tested.

PMID- 18038539
TI  - [Characteristic of the etiologic structure of acute enteric infections in adults
      based on the data from infectious diseases hospital].
AB  - Study of the etiologic spectrum of sporadic cases of causative agents of acute
      enteric infections (AEI) in 753 patients aged 15-85 years old using polymerase
      chain reaction (PCR) was performed in the infectious diseases hospital during 12
      months. It was shown that detection of the causative agents of AEI by PCR was 2.2
      times more effective than routine microbiologic diagnostics supplemented with
      test of feces on rotavirus by ELISA method and allowed to detect etiologic agent
      in 54.3% of the patients. Viral etiology of AEI was determined in 22.6% of the
      patients. The most significant causative agents of AEI comparable on the rate of
      detection with salmonella and shigella were genotype 2 noroviruses and group A
      rotaviruses which were isolated in 10.4 and 8.9% of the patients respectively.
      Seasonal change of dominating viral pathogens causing diarrheal diseases was
      noted: predominance of group A rotaviruses during winter-spring period,
      noroviruses--during spring-summer months, and astroviruses--during fall and in
      the beginning of winter.

PMID- 18038538
TI  - [Etiologic role of Corynebacterium non diphtheriae in patients with different
      pathology].
AB  - Bacteriologic examination of 1589 patients showed that, aside from C.
      diphtheriae, 11% of acute upper respiratory tract infections were caused by other
      Corynebacterium species. Such bacteria can cause infections of various
      localizations (bronchitis, pyelonephritis, urethritis, colpitis, dermatitis,
      arthritis, etc.). C. pseudodiphtheriticum and C. xerosis were isolated from
      clinical specimens most frequently. Corynebacterium spp. have adhesive,
      hemolytic, hemagglutinating, and neuraminidase activity; some of them are highly
      pathogenic. The most virulent, were following species: C. diphtheriae, C.
      pseudotuberculosis, C. urealyticum, and C. ulcerans. Corynebacterium non
      diphtheriae were frequently isolated from clinical specimens in association with
      staphylococci and streptococci. In such cases, factors of pathogenicity and
      resistance to antibiotics were more pronounced. Strains isolated with association
      with other bacteria have lost susceptibility to tetracycline, oleandomycin,
      penicillin, and erythromycin. It is important to be vigilant about bacteria from
      Corynebacterium genus in clinical settings, and thoroughly study their biologic
      characteristics, especially in immunocompromised patients.

PMID- 18038540
TI  - [Diagnostic value of persistent characteristics of staphylococci during their
      carriage].
AB  - Comparative assessment of information value of significant persistent
      characteristics of staphylococci in state of carriage was made, and the
      usefulness of these characteristics for creating diagnostic models was defined.
      One hundred and fifty strains of Staphylococcus aureus and S. epidermidis
      isolated from healthy persons with subsequent differentiation of carriage types
      were used in the study. It has been established that strains isolated from
      resident carriers more often have more markedly expressed factors of persistence.
      Ranking the factors of persistence of staphylococci according to their
      information value during carriage allowed to identifythe leading sign among them-
      anti-carnosine activity. Using factor analysis, obtained signs were united in the
      single complex defining bacterial carriage, which allows to build a mathematical
      model permitting to diagnose staphylococcal carriage with 95% probability.

PMID- 18038541
TI  - [Antimicrobial susceptibility and molecular mechanisms of resistance to beta
      lactams of gram-negative microorganisms--causative agents of nosocomial
      infections].
AB  - Profiles and mechanisms of resistance to beta-lactam antibiotics of isolates of
      Gram-negative microorganisms, which are causative agents of infections in
      Intensive Care Unit of hospital surgery department, were studied. Two hundred and
      ten clinical isolates were studied: Pseudomonas aeruginosa--86 strains (40.9%),
      Acinetobacter baummanii--45 strains (21.4%), Klebsiella pneumoniae--52 strains
      (24.8%), Escherichia coli--23 strains (11%), Enterobacter spp.--4 strains (1.9%).
      Profiles of antibiotic resistance were studied by the method of serial
      microdilutions; detection of most widespread and clinically significant genes of
      beta-lactamases of Gram-negative bacteria was performed by polymerase chain
      reaction. Carbapenems and cefoperazone/sulbactam were the most active
      antibiotics. Local features of distribution of beta-lactamase coding genes (TEM,
      SHV, CTX) in K. pneumoniae and E. coli isolates were revealed. Eleven strains of
      P. aeruginosa resistant to carbapenems and possessing genetic determinants of VIM
      group, which codes metallo-beta-lactamases, were isolated. Obtained data allows
      to assess the parameters of resistance to beta-lactam antibiotics and to reveal
      the main mechanisms of such resistance in etiologic agents of nosocomial
      infections, that, in its turn, allows to choose preparations for etiotropic
      therapy.

PMID- 18038542
TI  - [Duration of viral RNA circulation in blood of patients with hepatitis A].
AB  - Duration of hepatitis A virus (HAV) RNA circulation in blood of patients with HA
      was assessed and compared with intensity of cytolytic syndrome. Detection of
      viral RNA was performed by RT-PCR method with specific primers to VP1/P2A region
      of HAV genome. 54 blood serum samples from 40 patients were prospectively studied
      on the presence of HAV RNA. The latterwas detected in 53.7% of serum samples. The
      greatest number of positive results of HAV RNA detection in blood of the patients
      with HA was obtained from 8th to 21st day of illness (77.4%). Prolonged viremia
      (42+/-9 days) was observed in more than 20% of the patients. The maximal time of
      HAV RNA daetection in blood serum amounted 74 days (period of follow-up). HAV RNA
      was present in almost all patients with AIAT activity higher than 500 U/l
      regardless of duration of illness.

PMID- 18038543
TI  - [Molecular-epidemiological characteristic and possible origin of Vibrio cholerae
      non O1/non O139 with complete and limited set of virulence genes].
AB  - Study of molecular-epidemiological characteristics of Vibrio cholerae non O1/non
      O139 serogroup with complete and limited set of virulence genes was performed.
      Differences of their genes composition as compared to these of O1 serogroup
      (classic and El Tor biovars) were revealed, which points to their origin from
      avirulent environmental cholera vibrios.

PMID- 18038544
TI  - [Epidemiologic and etiologic characteristic of enterovirus infections in
      Khabarovsk region].
AB  - Results of epidemiologic, virologic, and serologic studies of enterovirus
      infections in Khabarovsk region from 1975 to 2006 were analyzed. Patterns of
      epidemic process of these infections were established: periodic change of
      dominating type of pathogen in the population; onset of the large epidemic peaks
      of incidence during emergence of circulation of new for the given area serotypes
      of enteroviruses; possibility of realization of several routes of virus
      transmission. Role of water factor in the progress of the epidemic process was
      revealed. Etiology of the large epidemic rise of aseptic meningitis incidence in
      Khabarovsk region in 2006 was established--the leading pathogens were ECHO
      viruses serotypes E6 and E30.

PMID- 18038545
TI  - [Paralytic poliomyelitis in Russian Federation in 1998-2005].
AB  - From 1998 through 2005 3,294 cases of acute flaccid paralysis (AFP) including 93
      cases with clinical picture of poliomyelitis were registered in Russian
      Federation. From the latter cases 91 were classified as vaccine-associated
      paralytic poliomyelitis (VAPP): 66 were VAPP cases in oral poliomyelitis vaccine
      (OPV) recipients and 25--VAPP cases in contacts. VAPP rate was 1 case per 1.6
      million of distributed OPV doses, 1 case per 2.2 million doses for OPV
      recipients, and 1 case per 186,000 doses for recipients of 1st OPV dose in
      children aged < 1 year. Majority of VAPP cases in recipients occurred after 1st
      dose (89.4%) and in contacts--in non-vaccinated children (76%). Mean interval
      between OPV administration and onset of VAPP in recipients was 21 days. Children
      aged < 1 year were predominant among VAPP cases (92.4% among recipient VAPP
      cases, and 80% among contact VAPP cases). Majority of the patients had
      unfavorable health status including defects of immunity. Most of poliovirus
      strains isolated from VAPP cases belonged to type 3 (52.9%) whereas to type 2 and
      1--29.8% and 17.4% of strains respectively. All VAPP cases were associated with
      vaccine-derived polioviruses. A highly diverged poliovirus type 1 (2.65% of
      nucleotide substitutions in VP1 region) was isolated from patient with contact
      VAPP. Formation of poliovirus-neutralizing serum antibodies in children with VAPP
      including persons with immunodeficiency reflects the ability of the organism to
      produce specific antiviral immune response.

PMID- 18038546
TI  - [Protective properties of certain external proteins of group B streptococci].
AB  - On the basis of genes, which control synthesis of externally localized proteins
      of group B streptococci (bac and scaAB), recombinant polypeptides P6 and ScaAB
      were obtained. Data on protective activity of these polypeptides during
      experimental infection of immunized mice as well as in opsonophagocytic test on
      cultivated peritoneal macrophages are presented. It has been shown that
      protective effect of specific antibodies to P6 was dependent from intensity of
      immune response. Titer of specific IgG to P6 equal 1:25000 was protective for
      mice during challenge with LD50. During sublethal challenge level of humoral
      immunity determined both rate of microorganism elimination and degree of decrease
      of concentration of streptococci in the spleen. Recombinant polypeptide ScaAB
      also had marked protective activity and protective titer ScaAB-specific IgG was
      significantly lower compared with the first polypeptide (1:1600). It has been
      established that both types of antibodies have opsonizing activity against
      different strains of group B streptococci. Opsonizing properties of antibodies to
      P6 were restricted to Bac protein-producing streptococci whereas specificity of
      antibodies to ScaAB was not restricted by type and group borders. Opsonization of
      both group B and group A streptococci was revealed. It has been established that
      protective efficacy mediated by antibodies was dependent not only from their
      opsonizing characteristics but also from availability of protein antigens, which
      under certain conditions can be shielded by capsular polysaccharide. It has been
      assumed that vaccine preparation developed on the basis of polypeptides P6 and
      ScaAB is promising for further research.

PMID- 18038547
TI  - [Assessment of immunity and allergy after vaccination with dry combined anthrax
      vaccine].
AB  - Study of humoral immune response and allergy in recipients of dry combined
      anthrax vaccine was performed. Immune response was assessed by antibody titers to
      protective antigen and by index of preventive properties of blood serum (PPS) of
      recipients. Relation of index of PPS and antibody titers in blood serum of the
      donors was established. Distribution of erythrocyte antigens in recipients of
      live dry and combined anthraxvaccines depending on blood group, Rh-factor, and
      age was studied. It has been shown that 80% of recipients of dry combined anthrax
      vaccine formed potent immunity with its high level lasted for 8 months. Study of
      allergenic properties of the combined anthrax vaccine using registration of
      neutrophils chemiluminescence in vivo showed low level of sensitization of
      vacinees.

PMID- 18038548
TI  - [Pertussis toxin and cross-reactive antigens in dynamics of Bordetella pertussis
      cultivation].
AB  - Cultures of Bordetella pertussis from phases of exponential growth, retarded
      growth and from stationary phase were obtained during periodic dynamic
      cultivation. Preparations for intravenous immunization of rabbits were made from
      these cultures. Levels of IgG to pertussis toxin, cell walls preparations from 12
      bacterial species, 4 organo-specific antigens, and 7 organospecific human
      antigens were measured in obtained sera. It was shown that higher levels of IgG
      to pertussis toxin were found in sera of rabbits immunized with cultures from
      exponential growth phase whereas decrease of this level in 8 times was observed
      in sera of rabbits immunized with cultures from retarded growth phase or end of
      stationary phase. After immunization with culture from exponential growth phase
      increase of IgG levels to cross-reactive antigens was not observed compared to
      levels of these antibodies in control sera obtained before immunization. After
      immunization with cultures from retarded growth phase or end of stationary phase
      increase of IgG levels to preparations of cell walls of Staphylococcus aureus, S.
      epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, to denaturated DNA,
      elastin, and renal and liver microsomal fractions was detected compared to
      control sera. Described data can substantiate usefulness of obtaining the most
      specific diagnostic sera and test-systems using cultures of B. pertussis from the
      phase of exponential growth.

PMID- 18038549
TI  - [Analysis of cytokines in seminal plasma and blood sera of patients with chronic
      prostatitis during immunotherapy with natural complex of cytokines and
      antimicrobial peptides].
AB  - Levels of pro- and anti-inflammatory cytokines (TNFalpha, IL-6, IL-8, IL-10) were
      studied in blood sera and seminal plasma of healthy volunteers and patients with
      chronic bacterial prostatitis (CBP) or chronic abacterial prostatitis (CABP).
      Assessment of effect of immunotropic drug Superlymph with direct antimicrobial
      action for treatment of mentioned groups of patients was performed. It was shown
      that seminal plasma of patients with CBP and CABP contained higher levels of IL-6
      compared with healthy subjects. IL-8 level was increased in small part of
      patients with CBP and CABP. Changes in cytokine status of patients with CBP and
      CABP that occurred during treatment and manifested in decrease of proinflammatory
      cytokines levels (IL-6 and IL-8) and increase of antiinflammatory cytokine level
      (IL-10) point to reduction of inflammatory process in prostate. Clinical effect
      of complex treatment in patients with CBP considering eradication of pathogen and
      shortening of duration of antibacterial treatment amounted 95%. Monotherapy of
      patients with CABP with Superlymph was effective in 72%.

PMID- 18038550
TI  - [Role of nuclear factor-kappaB in providing interactions of human neutrophils and
      epithelial cells from oral cavity with Candida albicans].
AB  - Contribution of intracellular signal pathways associated with nuclear factor
      kappaB (NF-kappaB) in realization of interactions of human neutrophils and
      epithelial cells from oral cavity with Candida albicans was studied. Supression
      of NF-kappaB in epitheliocytes resulted in decreased adsorption of C. albicans to
      buccal cells (buccal mucosa). Inhibition of NF-kappaB led to decrease in receptor
      dependent oxidative activity of neutrophils in systems with native and IgG
      opsonized C. albicans as well as to increase of phagocytic activity during
      contact with C3b-/iC3b-opsonized C. albicans. It has been concluded that NF
      kappaB participates in regulation of specific interactions of neurophils and
      epitheliocytes with C. albicans.

PMID- 18038551
TI  - [Real-time multiplex PCR for rapid detection of enteroviruses, adenoviruses and
      hepatitis A virus in clinical specimens].
AB  - Real-time multiplex polymerase chain reaction (PCR) with internal positive
      control (IPC) was developed for simultaneous detection of adenoviruses (AV),
      enteroviruses (EV) and hepatitis A virus (HAV). Primes and probes labeled with
      different fluorophores (FAM, R6G, ROX, and Cy5) and able to detect up to four
      viral RNAs (DNAs) with high specificity in a single tube in real-time PCR were
      designed. Sensitivity and specificity of the method was estimated using cultural
      strains of 8 serotypes of EV, 5 serotypes of AV and 2 clinical specimens
      containing HAV. Sensitivity of the method for detection of polioviruses types 1,
      2, and 3 (Sabin vaccine strains) was 0.5--1 TCID50 per reaction mixture. Thirty
      clinical specimens were analyzed by the multiplex PCR with and without IPC, and
      by mono-specific PCR. Comparison of these methods with cultural one revealed
      results agreement in 86.7% in case of multiplex PCR with IPC and in 100% in case
      of multiplex PCR without IPC and mono-specific PCR. This method can be used for
      rapid diagnostics of enteric viral infections as well as for determination of
      viral contamination level of water. As intermediate results of the study the
      methods for quantitative assessment of HAV, AV, and EV nucleic acids were
      developed which are convenient tools for the control of antiviral therapy
      effectiveness.

PMID- 18038552
TI  - [Experimental grounds for the effectiveness of ciprofloxacin and oxytocin
      combined use].
AB  - In order to determine the influence of combined use of ciprofloxacin and oxytocin
      on susceptibility of microflora to antibiotics as well as level of microbial anti
      lysozyme (ALA) and anti-complement activity (ACA) 148 anaerobic and aerobic
      microorganisms were isolated from 80 patients with purulent infections of soft
      tissues. Susceptibility of staphylococci, streptococci, and enterobacteria to the
      most commonly used antibiotics was assessed by agar-diffusion method with
      standard disks. ALA and ACA of the isolated strains were defined by routine
      methods. Minimal inhibitory concentration (MIC) of ciprofloxacin and oxytocin for
      isolated pathogens were determined according to standards of NCCLS. Influence of
      oxytocin on MIC of ciprofloxacin was determined as well as inhibitory effect of
      the latter on factors of bacterial persistence. Decrease of MIC of ciprofloxacin
      as well as increase of its inhibitory effect on pathogens' ALA and ACA when it
      used in combination with oxytocin were noted. Usefulness of combined use of
      ciprofloxacin and oxytocin for treatment of different infections has been
      proposed.

PMID- 18038553
TI  - [Plasmid analysis of bacteria of Bacillus genus used in the development of
      probiotics].
AB  - Presence of plasmid-contained strains in probiotics prepared on the basis of
      Bacillus bacteria was assessed. Plasmid analysis was performed by the method
      based on neutralization of bacterial suspension after alkaline treatment with
      lithium chloride. Presence of 4-6 plasmids with molecular weight from 1 to 75 MDa
      was revealed in 4 commercially available probiotics. Since plasmids can
      facilitate transfer of genes of the antimicrobial resistance to pathogenic
      microorganisms it was recommended to perform thorough search of probiotic
      microorganisms without plasmids or ensure the elimination of R-plasmids in start
      cultures for the most promising biopreparations.

PMID- 18038554
TI  - [Changes in electrophysical characteristics of Azospirillum brasilense Sp7 cells
      during their interaction with polyclonal antibodies].
AB  - Electrooptical characteristics of Azospirillum brasilense Sp7 cells during their
      specific interaction with polyclonal rabbit antibodies were studied. Dependence
      of optical density of cell suspension during electroorientation of cells from
      frequency of orienting field in interval 10, 100, 250, and 500 kHz was evaluated.
      Itwas shown that electrooptical (EO) characteristics of bacterial suspensions
      change during interaction of A. brasilense cells with antibodies, and maximal
      changes occur when frequency of oriented field amounts 100-250 kHz. During
      interaction of A. brasilense Sp7 with strain-specific polyclonal antibodies in
      the presence of Escherichia coli K-12 and Pseudomonas putida C-11 decrease of
      amplitude of analytic signal was observed but detection of A. brasilense Sp7
      cells was possible. Possibility of detection of microorganisms by EO analysis
      during their interaction with antibodies was shown.

PMID- 18038555
TI  - [State of several parts of immune system in mice, infected by enterotoxigenic
      bacteria of Enterobacter genus].
AB  - Influence of thermolabile enterotoxin bacteria of Enterobacter genus on the
      immune system of mice was studied. Assessment of phagocytic functions of the
      immune system as well as antigen-presenting functions of macrophages during
      infection with enterotoxin-producing strains of bacteria from Enterobacter genus
      revealed pleiotropic effect of the toxin which is characterized by inhibition of
      antigen-presenting and processing functions of macrophages.

PMID- 18038556
TI  - [Immunologic parameters of monkeys infected by urogenital mycoplasmas].
AB  - In monkeys contained in captivity conditions in open-air cages or in group cages
      human mycoplasmas are often detected: antigens of Mycoplasma hominis in blood
      serum were revealed in 33.3% of cases, and antibodies to it--in 15.6% of cases.
      IgM to M. hominis were detected more often than IgG. In 8 monkeys both types of
      immunoglobulins were detected. Rates of detection of Ureaplasma urealyticum
      antigens and specific antibodies were 43.1% and 31.1% respectively, and IgG were
      found more frequently than IgM (in 22 cases both types of immunoglobulins were
      revealed). High rates of M. hominis and U. urealyticum antigens and antibodies
      detection in blood serum of both healthy monkeys and monkeys with urogenital
      tract diseases show prevalence of human mycoplasmas carriage among monkeys
      contained in captivity conditions.

PMID- 18038557
TI  - [Immunity to antigens of nontypeable Haemophilus influenzae strains].
AB  - Nonencapsulated (nontypeable) Haemophilus influenzae (NTHi) is a Gram-negative
      coccobacillus colonizing upper respiratory tract of most healthy people and
      causing such diseases as otitis media, sinusitis, exacerbations of chronic
      obstructive pulmonary disease, and bronchitis. NTHi may cause systemic infection.
      As a result, over the past decade the bacterium has been the subject of intense
      research. However immune response to NTHi has not been well characterized. Data
      on research of immune response to NTHi are presented.

PMID- 18038558
TI  - [The importance of S. P. Botkin's scientific ideas for 21th century medicine].

PMID- 18038559
TI  - [Botkin, an outstanding doctor and master of diagnosis, in the eyes of his
      friends and patients].

PMID- 18038560
TI  - [The role of the Chronobiology and Chronomedicine Problem Board of Russian
      Academy of Medical Sciences in the development of internal medicine (on the
      occasion of its 25th anniversary) ].

PMID- 18038561
TI  - [Correction of androgen deficiency in elderly patients].
AB  - In spite of its prevalence, age-related androgen deficiency has not been studied
      in full. Androgen deficiency is associated with a lot of age-related diseases
      (coronary artery disease, arterial hypertension, obesity, diabetes mellitus,
      osteoporosis etc). The level of testosterone in men gradually decreases beginning
      at the age of 30 to 40 years. Age-related hypogonadism results in an increase in
      the frequency of cardiovascular diseases and cardiovascular mortality. Low
      testosterone level is associated with dyslipidemia, atherosclerosis, reduction of
      fibrinolysis, insulinoresistance, and abdominal obesity. Physiological doses of
      androgen preparations are supposed to have a positive effect on various chains of
      metabolism and improve the course of diseases in men.

PMID- 18038562
TI  - [Prevention of and coping with professional stress].
AB  - The article reviews publications dedicated to stress, especially professional
      one. The authors describe a severe form of stress, emotional burning-out
      syndrome, which is often found in doctors and nurses dealing with patients
      suffering from mental disorders, oncological diseases, AIDS, and those who are
      treated in intensive care units. Recommendations concerning stress prevention and
      medication support able to prevent or lower pathological consequences of chronic
      working stress are given.

PMID- 18038563
TI  - [Prevalence of cholelithiasis in different regions].
AB  - The review characterizes the prevalence of cholelithiasis in Russia and other
      countries taking into account the evolution of diagnostic methods from necropsy
      to billiary tract ultrasonography. The authors demonstrate the dynamics of
      cholelithiasis prevalence in different world's regions, climate-geographic zones,
      urban and rural areas, as well as the growth of cholelithiasis incidence in
      Russia and the world during the 20th century. The results of clinical and
      epidemiological studies on the prevalence of cholelithiasis among aborigines and
      non-aborigines of Chukotka, Republic of Sakha (Yakutia), Khakasia, and North and
      South America are given.

PMID- 18038564
TI  - [Erythropoietin in clinical practice].
AB  - In numerous studies, erythropoietin (EP) has been shown to be a "universal"
      protective tissue cytokine, and EP receptors have been shown to exist in a lot of
      tissues. The pleiotropic effects of EP (the anti-inflammatory effect,
      angiogenesis, anti-apoptosis etc.) make clinical application of EP (especially
      recombinant EP, REP, and EP analogs without erythropoietic activity) promising in
      different diseases. Possibilities provided by REP application in neurology,
      cardiology, hematology, oncology, and other clinical areas are being studied
      intensively. Clinical studies of EP are now solitary, and they should be
      continued; new EP analogs with specified qualities and selective mechanisms of
      action should be developed. This review discusses the modern state of EP
      investigation and possibilities provided by its clinical application.

PMID- 18038565
TI  - [The chronobiological conception of the development of acute myocardial
      infarction].
AB  - The subjects, 1048 patients with acute myocardial infarction (AMI), were examined
      in order to study the chronobiological periodicity of acute coronary
      catastrophes. The study established that the probability of AMI was the lowest on
      Sundays and Saturdays, equally higher on Mondays, Wednesdays, and Thursdays,
      lower on Tuesdays, and the highest on Fridays. Analysis of circannian AMI
      incidence demonstrates that its probability decreases in September and increases
      in February, March, May, and June. In August and November, the incidence of
      different AMI forms differs: transmural forms prevail in August, while large
      focal ones prevail in November.

PMID- 18038566
TI  - [On the use of statins in patients with chronic cardiac insufficiency].
AB  - Today, the necessity to use hypolipidemic agents belonging to the group of
      statins as means of primary and secondary prevention of coronary artery disease
      (CAD) and its complications is not doubted. The results of numerous large studies
      conducted in many different countries during the last 10 to 15 years confirm this
      statement. The appropriateness of statin application to patients with chronic
      cardiac insufficiency (CCI) is still under discussion, because there are no
      sufficient data on whether hypolipidemic therapy is able to improve the prognosis
      in this category of patients. The authors conducted a long-term research into the
      use of statins in combination with basic combined therapy in patients with CCI
      complicating the course of CAD. A reverse correlation between the levels of total
      cholesterol, low-density protein cholesterol, and the degree of CCI severity was
      demonstrated. Long-term continuous therapy of CCI patients with a combination of
      medications including statins did not worsen the clinical symptoms. However,
      hypolipidemic therapy should be administered to CCI patients on a differentiated
      basis, taking into account the initial state of lipid profile and the severity of
      the underlying disease.

PMID- 18038567
TI  - [The clinical features of arterial hypertension complicated by an old ischemic
      cerebral stroke].
AB  - The course of arterial hypertension (AH) was evaluated retrospectively in 306
      patients, who had undergone annual hospital examination and treatment during the
      previous five years. After five years, AH had got complicated with ischemic
      cerebral stroke (ICS) in 147 patients (group 1). AH had not got complicated with
      ICS in 149 patients (group 2). These patients had been observed for another five
      years. By the end of the study, 98 patients had remained in group 1, and 100
      patients had remained in group 2. Mean term of observation had been 10.3 +/- 0.8
      years in group 1, and 10.1 +/- 0.9 years in group 2. Clinico-anamnestic analysis
      revealed the following peculiarities of the course of AH complicated by ICS: a
      longer AH course before the development of ICS; faster deterioration of AH in a
      period of 10 years; faster deterioration of chronic cardiac insufficiency and
      discirculatory encephalopathy; more frequent combination with coronary heart
      disease and carbohydrate exchange; more frequent development of transitory
      ischemic attacks (TIA); TIA became more frequent before the development of ICS;
      in 70% of group 1 patients TIA was located in the place of a future ICS. The
      authors suggest that slowly and quickly progressing AH forms should be
      differentiated according to the progression of the risk of cardiovascular
      complications.

PMID- 18038568
TI  - [The effects of various factors on long-term outcomes of non-stable stenocardia].
AB  - The article presents the results of one-year observation of 472 patients who
      experienced non-stable stenocardia in 2003-2004. During this period, exacerbation
      of coronary artery disease with or without acute coronary catastrophe was noted
      in every third patient. Thirty-three cases of acute coronary pathology were
      registered. Year lethality was 27.3%, with acute myocardial infarction as the
      leading cause of death. By step-wise diagnostic regression method it was proved
      that old myocardial infarction was the only factors that had a significant
      negative effect on the long-term prognosis of non-stable stenocardia.

PMID- 18038569
TI  - [Early and progressing alcohol cardiomyopathy].
AB  - The subjects of the study were 10 young men who had taken about 40 g of alcohol
      (group 1) and 26 ones who had taken more than 80 g (group 2) one day before the
      hospitalization. Heart changes on days 3, 4, and 5 after the alcohol intake were
      studied using ECG, radiography, and ultrasonography; some functional tests
      reflecting hepatic and renal condition were performed as well. No changes were
      found in group 1, while certain functional ECG changes were revealed in group 2
      patients; these changes were associated with acute toxic alcohol myocardial
      dystrophy. Group 3 consisted of subjects aged 53 +/- 1 years who had been taking
      120 to 160 g of alcohol a week systematically for not less than 5 to 8 years.
      These subjects displayed signs of mental depression and progressing alcohol toxic
      cardiomyopathy (constant atrial fibrillation, cardiac blockade, cardial
      enlargement, and signs of circulatory insufficiency). Four subjects died as a
      result of alcohol abuse.

PMID- 18038570
TI  - [The condition of external respiratory mechanics in patients with type 1
      diabetes].
AB  - External respiratory mechanics was studied in 141 patients with type 1 diabetes
      mellitus (DM1) and 36 healthy controls using computed analysis of flow-volume
      loop and total body plethysmography. The DM1 patients were divided into 4 groups:
      group 1 consisted of patients without clinical signs of microangiopathic
      complications; groups 2 and 3 consisted of patients with initial and advanced
      manifestations of late diabetic syndrome (LDS), respectively; group 4 consisted
      of patients suffering from severe endocrinopathy with end-stage chronic renal
      failure. The velocity and volume parameters in groups 1 and 2 did not differ
      significantly from those in the controls. Significant reduction in the vital
      capacity, forced expiratory volume in one second, and total lung capacity was
      noted in patients with advanced LDS and uremia. Forced expiratory volume in one
      second decreased in proportion to reduction in lung vital capacity, which did not
      cause Tiffno index to leave the reference range. The authors came to the
      conclusion that DMI causes restrictive ventilatory defect, associated with
      advanced clinical manifestations of microangiopathic alterations.

PMID- 18038571
TI  - [The effect of intravenous laser irradiation of blood on the system hemodynamics
      of patients with chronic obstructive bronchitis exacerbation].
AB  - The aim of the study was to evaluate the effects of intravenous laser irradiation
      of blood (ILIB) on system hemodynamics in patients with chronic obstructive
      bronchitis (COB) exacerbation. Ninety-seven patients with COB exacerbation were
      divided into two comparable groups. The 47 patients of the control group received
      conventional medication, while the 50 patients of the main group received the
      same therapy plus ILIB, which consisted of 10 everyday 20-min procedures. Central
      hemodynamic variables were measured prior to and after the treatment. The results
      demonstrated higher effectiveness of COB treatment when ILIB was applied and that
      ILIB itself had a positive effect on system circulation in COB exacerbation by
      changing hyperkinetic hemodynamics into normokinetic one. The study shows that it
      is appropriate to include ILIB into treatment of COB.

PMID- 18038572
TI  - [The diagnostic value of the detection of hepatic fibrosis serum markers in
      chronic viral hepatitis].
AB  - The diagnostic significance of serum markers of fibrosis was investigated in 92
      patients with chronic viral hepatitis (CVH) by studying the collagenolythic
      activity of blood, proteasic inhibitor activity, collagen metabolism products
      (oxyproline fraction), and fibronectin. At the same time, the patients underwent
      puncture biopsy of the liver, which made it possible to determine the degree of
      process activity and the stage of its chronization. As the degree of fibrosis
      grew, the collagenase serum activity increased significantly, while the alpha1
      proteinase inhibitor activity fell, the content of oxyproline (its fractions)
      increased, and the fibronectin level decreased. Hence, the measurement of the
      noted parameters allows for noninvasive diagnostics of CVH stages.

PMID- 18038573
TI  - [Osteoarthrosis of the knee joints in climacteric women with excessive body
      weight or obesity].
AB  - The purpose of the study was to evaluate body weight (BW) effect on the frequency
      and clinical manifestations of knee joint osteoarthrosis (KJOA) in climacteric
      women with excessive BW or obesity. The subjects of this case control study were
      divided into three groups: group 1 consisted of 283 climacteric women with normal
      BW; group 2 consisted of 283 women with excessive BW; 283 obese women constituted
      group 3. All the three groups were comparable by age and menopause duration. The
      diagnosis of KJOA was established according to American Rheumatology Association
      criteria. Joint pain intensity was assessed using 100-mm visual analog scale.
      Lequesne algofunctional index was used to determine functional limitations. Lipid
      and carbohydrate exchange parameters were studied as well. The frequency of KJOA
      was significantly higher in group 2 (47.3%) and group 3 (56.1%) vs. group 1
      (39.9%). Abdominal obesity was significantly more frequent in patients with KJOA
      (32.2%). Obesity was associated with an increased risk of KJOA (relative risk =
      1.91; 95% confidence interval = 1.37-2.67), but not other variants of
      osteoarthrosis. Thus, in Russian population of climacteric women the frequency of
      KJOA was significantly higher in those with excessive body weight or obesity vs.
      women with normal body weight. Abdominal obesity was found to be an independent
      risk factor of KJOA, but not other localizations of osteoarthrosis.

PMID- 18038574
TI  - [The characterization of the intestinal microflora in patients with extrahospital
      pneumonia].
AB  - One hundred and sixty patients, including 130 patients with extrahospital
      pneumonia (EHP), were examined. The control group consisted of 30 practically
      healthy subjects. All the EHP patients (86 males and 44 females aged 18 to 70
      years) underwent complex clinicolaboratory examination. The results of ECG and
      chest radiography were taken into consideration in addition to complaints,
      disease history, and objective parameters to characterize the degree of EHP and
      the phase of the process. The qualitative and quantitative compositions of the
      intestinal microflora were studied according to recommendations of USSR Public
      Health Ministry (1987) using Russian nutrient media and reagents. The degree of
      dysbacteriosis was determined according to the classification by I. B. Kuvayeva
      et al. (1991), supported by other researchers. Some qualitative and quantitative
      changes in the obligatory and facultative intestinal microflora were found in
      42.3% of EHP patients. Intestinal dysbacteriosis was revealed in 8.3% of patients
      with mild EHP, in 34.8% of patients with moderate EHP, 52.8% of patients with
      severe EHP, 86.1% of patients with protracted EHP, and 64.5% of patients with
      complicated EHP. Thus, EHP in most patients was accompanied by more or less
      severe intestinal microflora disturbances, which frequently were of latent
      character. The degree of dysbacteriosis tended to grow along with the severity of
      the disease.

PMID- 18038575
TI  - [The place of the biopsy and morphological study of hepatic tissue in children
      and adults in the clinician's practice].
AB  - The authors analyze their own (more than 2500 manipulations in children and
      adults) and foreign experience in hepatic biopsy, and describe the most wide
      spread techniques of puncture biopsy, paying special attention to complications
      of the manipulation and ways of their prevention. Indications and contra
      indications to biopsy in children and adults are defined; the role of
      morphological studies in diagnostics of chronic hepatic diseases is discussed.

PMID- 18038576
TI  - [Teaching nephrologists modern techniques of radiodiagnostics of renal diseases].

PMID- 18038577
TI  - [Cirrhotic cardiomyopathy].
AB  - Modern studies have shown that hepatic cirrhosis (HC) is accompanied by moderate
      cardiac dysfunction. The character and degree of these changes do not depend on
      the etiology of HC and manifest by an increased ventricular wall thickness and
      diastolic dysfunction, which deteriorate with ascite and physical labor, as well
      as basal hyperdynamic systolic dysfunction with pathologic response to physical
      stress. The latter decreases physical tolerance, which contributes to the
      development of chronic fatigue syndrome and lowered working ability in HC
      patients. Cardiovascular changes get reversed in 6 to 12 months after hepatic
      transplantation.

PMID- 18038578
TI  - [Treatment of arterial hypertension: current conception].

PMID- 18038579
TI  - [Changes of spiroergometric parameters in males under 30 years of age with a
      hypertensive reaction of arterial pressure to graduated exercise].
AB  - AIM. To study changes in blood pressure (BP) and spiroergometric parameters in 18
      30-year-old males with normal BP at rest having different reactions of BP to
      graduated exercise. MATERIAL AND METHODS: Forty two male examinees performed
      treadmill-test according to R. Bruce protocol with measurements of BP, ECG
      parameters and gas composition of exhaled air. RESULTS: The treadmill test has
      shown that 20 (47.6%) males had a normotensive reaction of BP to exercise, 22
      (52.4%)--a hypertensive reaction. The latter had higher systolic and/or diastolic
      BP levels than those normal for performance of treadmill test. Significantly
      higher were also parameters of pulmonary ventilation, oxygen pulse in combination
      with large consumption of O2 and expiration of CO2. CONCLUSION: The presence of
      significant differences by spiroergometric indices in males with normotensive and
      hypertensive reactions of BP to exercise but normal BP at rest reflects metabolic
      shifts at early stages of hypertension in the latter.

PMID- 18038580
TI  - [Administration of cardioselective beta-adrenoblockers in patients with arterial
      hypertension and/or ischemic heart disease associated with bronchoobstructive
      syndrome].
AB  - AIM: To assess efficacy and safety of selective beta-adrenoblockers (BAB)
      metoprolol succinate and nebivolol in patients with arterial hypertension (AH)
      and/or IHD associated with bronchoobstructive syndrome (BOS). MATERIAL AND
      METHODS: Fifty patients suffering from AH and/or IHD associated with BOS in
      chronic obstructive pulmonary disease (COPD) and/or bronchial asthma (BA) of any
      severity in remission received BAB. Safety of BAB was evaluated by dynamics of
      respiratory symptoms and bronchial patency. An antihypertensive effect of BAB was
      assessed by the data of 24-h monitoring of BP, an antianginal one--by dynamics of
      clinical symptoms, amount of nitrates taken and exercise tolerance (6-min walk).
      The results of Holter ECG monitoring and an antiarrhythmic effect of BAB were
      also studied. RESULTS; Metoprolol succinate and nebivolol did not deteriorate
      bronchial patency (baseline FEV1--81.08 +/- 22.57%, at the end of the study-
      84.58 +/- 23.72% and 71.12 +/- 19.95, 73.19 +/- 21.70, respectively) in COPD
      and/or BA. Both drugs showed high antihypertensive efficacy as monotherapy and in
      combined therapy. Anginal attacks severity and frequency reduced significantly.
      The need in nitrosorbide fell noticeably, exercise tolerance increased
      significantly. Metoprolol succinate and nebivolol have a good anti-arrythmic
      effect. CONCLUSION: Metoprolol succinate and nebivolol are safe in patients with
      bronchoobstructive syndrome and AH and/or IHD in the presence of cardiovascular
      indications; these drugs can be used in patients with severe COPD and BA as well
      as their exacerbations unrelated to administration of beta-adrenoblocker.

PMID- 18038582
TI  - [Five-year results of implementation of the federal target program Prevention and
      Treatment of Arterial Hypertension in Russian Federation (2002-2006)].

PMID- 18038581
TI  - [Pharmacokinetics of enalapril and metoprolol in hypertensive patients with
      hepatic pathology].
AB  - AIM: To examine characteristics of pharmacokinetics and pharmacodynamics of
      enalapril and metoprolol in hypertensive patients with gastrointestinal diseases
      to make relevant corrections in the treatment. MATERIAL AND METHODS: The study
      included 36 hypertensive patients with steatosis, hepatic cirrhosis and ulcer.
      All the patients received metoprolol or enalapril. Concentrations of metoprolol
      and enalaprilate (active enalapril metabolite) were determined with high
      performace liquid chromatography. The findings gave grounds for calculation of
      mean drug retention time (MRT) and area under curve "concentration-time" (AUC).
      Efficacy of the drugs was estimated by the data of 24-h blood pressure
      monitoring. RESULTS: Hypertensive patients with hepatic diseases given enalapril
      exhibited lowering of maximal concentration (C(max)) of enalaprilate and
      prolongation of time of its reaching (T(max)) compared to ulcer patients. MRT and
      AUC were increased in hepatic cirrhosis patients treated with enalapril and
      metoprolol. Metoprolol C(max) in this group of patients was higher than in the
      controls. Blood pressure monitoring showed that enalapril therapy was more
      effective in ulcer patients vs patients with liver diseases. Metoprolol treatment
      of hypertensive patients with hepatic cirrhosis resulted in development of
      bradycardia. CONCLUSION: In hypertensive patients with liver diseases on
      enalapril therapy its metabolite production may appear insufficient for
      therapeutic effect and higher dose may be needed. Metoprolol in the treatment of
      hypertensive patients with hepatic cirrhosis should be used with caution because
      of disturbance of its metabolism and possible cumulative effects.

PMID- 18038583
TI  - [Prospective assessment of a training effect in correction of endothelial
      dysfunction and atherosclerosis risk factors in students (results of examination
      of Tomsk male students)].
AB  - AIM: To assess a training effect correcting endothelial dysfunction (ED),
      neurovegetative status and atherosclerosis risk factors (ARF) in male students.
      MATERIAL AND METHODS: Ninety healthy students aged 18-25 years with ARF and ED
      were followed up after bicycle exercise (BE) 3 times a week: 30 males did BE for
      1 month, 30--for 2 months and 30--for 3 months. Blood lipids, exercise tolerance
      (ET), parameters of cardiointervalography, dopplerangiography of the brachial
      artery and rheovasography of the forearm at rest and in tests with reactive
      hyperemia, hyperventilation were estimated immediately after, 1 and 3 months
      after BE. RESULTS: Two-month BE forms adequate structural trace the effect of
      which can be partially found 3 months later. Three-month BE tells on adaptation
      as it produces proatherogenic shifts in blood lipids. After the two-month cycle
      of BE positive effects regress in the following order: normalization of blood
      lipids, improvement of vegetovascular reactivity, high exercise tolerance and
      endothelium-related vasodilation. CONCLUSION: Two-month exercise is effective and
      safe, forms adaptive reserve of the body, structural effect of which partially
      persists for 3 months.

PMID- 18038584
TI  - [Phenotypical features of a heterozygous form of familial hypercholesterolemia].
AB  - AIM: To conduct a quantitative and qualitative analysis of phenotypical
      manifestations in patients with a heterozygous form of familial
      hypercholesterolemia (FHC) and to reveal factors involved in their development.
      MATERIAL AND METHODS: A total of 247 patients with a clinical diagnosis of
      heterozygous FHC participated in the trial. Clinical manifestations of the
      disease in men and women were analysed and compared. Blood lipids were compared
      to those in the controls. A correlation analysis was used to reveal correlations
      between symptoms of the disease and lipid levels in the blood. RESULTS: Tendon
      xanthomas were most frequent (79%) clinical sign with location primarily in
      Achilles' tendon. Incidence of basic clinical manifestations increased with age
      and significantly correlated with LDLP cholesterol. Two clinical signs were seen
      in 1/3 of the patients, three--in 13% (sex differences were insignificant). Mean
      levels of total cholesterol and LDLP serum cholesterol in heterozygous patients
      were 1.9 and 2.5 times higher than in the controls. Total cholesterol was
      significantly higher in women. A mean level of HDLP cholesterol was significantly
      lower while triglycerides were higher than in the control group. The disease
      symptoms manifested in men 5 years earlier than in women, FHC was diagnosed in
      men 7.5 years earlier. CONCLUSION: Patients with heterozygous FHC are
      characterized by higher levels of LDLP cholesterol, lower level of HDLP
      cholesterol and higher triglycerides in the serum than in healthy controls. Sex
      related differences by severity and prevalence of basic symptoms in heterozygous
      FHC patients were not found. The time of clinical symptoms appearance and
      diagnosis evidences for more rapid progression of the disease in men.

PMID- 18038585
TI  - [New facts about pathogenesis of atrial fibrillation: correlation between changes
      in bioelectric brain activity and recurrence of atrial fibrillation paroxysms].
AB  - AIM: Determination of neurophysiological features of the disease course in
      patients with paroxysmal atrial fibrillation (AF); pathogenetic validation of use
      and assessment of therapeutic efficacy of clonazepam (an atypical agonist of
      benzodiazepine receptors) in combined antiarrhythmic therapy. MATERIAL AND
      METHODS: The study group consisted of 31 patients with paroxysmal AF free of
      severe organic changes of the myocardium with twice a week paroxysms, on the
      average, treated ineffectively with beta-adrenoblockers, amiodaron, sotalol,
      etacisine, allapinin or combination of the above drugs. A comparative group
      consisted of 10 patients with perpetual arrhythmia. Fifteen healthy subjects
      entered the control group. Electroencephalograms were made on the unit Brain
      Surfing (Russia). Compression-spectral analysis was conducted with utilization of
      Fourier's algorithm in different periods of the disease for calculation of the
      absolute (mcV2/Hz) spectral power of the teta- (4.0-7 Hz), alpha (8-13 Hz) and
      beta-rhythm (14-18 Hz). Clonazepam was given in a dose 1.5 mg/day in addition to
      insufficiently effective anti-arrhythmic therapy. Holter ECG monitoring was
      carried out initially and in therapy with clonazepam. RESULTS: The spectral power
      of alpha-, beta- and teta-rhythm of patients with paroxysmal AF exhibits
      significant cyclic fluctuations depending on the disease course period. In attack
      free period AF patients differ from healthy subjects by a significant fall of
      spectral power of beta-rhythm indicating functional deficiency of the reticular
      formation in this disease. 0-24 hours before AF paroxysm spectral power of all
      the rhythms rose greatly reflecting marked functional disintegration of
      nonspecific brain systems realizing psychovegetative regulation. At AF paroxysm
      spectral power of alpha- and beta-rhythm significantly decreased while that of
      teta-rhythm grew (activation of the lymbic complex). 0-24 h after paroxysm
      spectral power of alpha- and beta-rhythm continued to fall, of teta-rhythm-
      sharply fell. Spectral EEG characteristics in this period maximally approached
      those of the control group. Clonazepam treatment decreased the paroxysms two
      times and more in 58.1% patients. Holter ECG showed associated reduction in the
      number of supraventricular extrasystoles by 81.9%. The compression-spectral ECG
      analysis revealed a 12% enhancement of beta-rhythm spectral power showing
      lessening of functional disintegration of nonspecific brain systems. CONCLUSION:
      The course of paroxysmal AF is characterized by functional disintegration of
      nonspecific brain systems (thalamo-cortical, lymbic and mesencephalic reticular
      formation) which is maximally evident before AF paroxysm and attenuates after it.
      Cyclic changes in functional activity are a neurogenic factor realizing readiness
      of the atria to fibrillation. An atypical agonist of benzodiazepine receptors
      clonazepam effectively influences neurogenic mechanisms provoking AF paroxysms.

PMID- 18038586
TI  - [Calcified aortal stenosis and osteoporosis: bone metabolism of systemic calcium
      metabolism in the elderly].
AB  - AIM: To examine bone tissue, systemic calcium metabolism and bone remodeling in
      patients with calcified aortal stenosis of degenerative origin (DAS). MATERIAL
      AND METHODS: The examination of 310 patients (mean age 73.2 years) was made with
      application of questioning, echocardiography, double energetic x-ray
      absorptionmetry, measurements of C-telopeptides, osteocalcin, vitamin D,
      parathyroid hormone with solid phase enzyme immunoassay. RESULTS: Bone tissue
      mineral density (BTMD) was abnormal in 71% of examinees (osteopenia--40%,
      osteoporosis--31%). Vitamin D concentration under 50 nmol/l was in 76.3%,
      parathyroid hormone elevated above 100 pg/ml in 15.8% patients. CONCLUSION: The
      severity of lumbar spine affection depended on severity of calcinosis of aortic
      valve, was associated with lowering of osteosynthetic activity and was not
      associated with the presence of osteoporosis risk factors, constitutional
      parameters, calcium metabolism changes. This suggests the existance of a special
      form of BTMD disorder in elderly patients with aortal stenosis.

PMID- 18038587
TI  - [Characteristics of cardiomyopathy in recessive X-linked myodystrophy with a
      rapid and slow course].
AB  - AIM: To specify cardiomyopathy development in two types of myodystrophy--with
      complete and partial absence of dystrophin--for detection of the role of genetic
      and environmental impacts. MATERIAL AND METHODS: Clinical, genetic and
      electrophysiological examinations, test for creatinphosphokinase (CPK) were made
      in 113 patients with recessive X-linked Duchenne myodystrophy (DMD) aged 7 to 20
      years and with Bekker's myodystrophy (BMD) aged 18 to 60 years. The control group
      consisted of 112 males matched by age and antropometric parameters. RESULTS: The
      patients were diagnosed to have left ventricular (LV) diastolic dysfunction of
      pseudonormal or restrictive type (in BMD patients dystrophy was less severe)
      without changes in LV geometry. There was dissociation between the lesion of the
      skeletal muscles and myocardial dystrophy showing a special role of dystrophin in
      the myocardium. Echocardiographic examination revealed early signs of heart
      trouble. CONCLUSION: Development of cardiomyopathy is characterized by
      development of diastolic dysfunction, then addition of excentric hypertrophy,
      later systolic dysfunction arises and growing dilation. Partial absence of
      dystrophin in BMD patients explains less severe structural and functional cardiac
      affection. The main marker of the course of myodystrophy is CPK. This parameter
      helps to evaluate the progress of the pathological processes in the skeletal
      muscles and myocardium. Electrocardiographic examination of these patients must
      be supplemented with echocardiography.

PMID- 18038588
TI  - [Detection of structural changes of large arteries by characteristics of
      peripheral pulse wave: comparison with high resolution ultrasonic investigation].
AB  - AIM: To compare high-resolution ultrasound of major arteries and the method of
      vascular stiffness evaluation by digital volume pulse photoplethysmography after
      sublingual nitroglycerin in diagnosis of structural vascular changes. MATERIAL
      AND METHODS: The comparison of the two methods was made in 110 volunteers (mean
      age 31.9 +/- 11.5 years). The study protocol included measurement of blood
      pressure (BP), blood lipids and glucose, evaluation of IMT of the carotid
      arteries by ultrasonography, baseline stiffness index (SIbl) and after sublingual
      nitroglycerin (SIng) by photoplethysmography. Reproducibility of
      photoplethysmography was evaluated in 20 volunteers (mean age 20.3 +/- 1.4 years)
      with repeated measurement after 1 week. The results were tested in 40 volunteers
      of different age groups. RESULTS: There were significant correlations of IMT,
      SIbl and SIng with risk factors and close interrelations of these parameters.
      SIng better explained variability of IMT compared to SIbl (r = 0.79, R2 = 0.62, p
      < 0.001 versus r = 0.67, R2 = 0.45, p < 0.001, respectively). Relations of IMT
      with risk factors were lost after correction for SIng. Reproducibility of SIng
      was higher than SIbl (+/- 5.1% versus +/- 10.9%, respectively) and than those for
      IMT found in the literature. Mean IMT values for random sample evaluated by
      ultrasonography and calculated by estimated equation of linear regression for
      SIng and IMT did not differ significantly (0.576 +/- 0.087 mm versus 0.570 +/-
      0.074 mm, p = 0.44; r = 0.71, p < 0.001, mean difference 0.007 +/- 0.051 mm).
      CONCLUSION: The method of vascular stiffness measurement is comparable with
      ultrasonography in terms of vessel structure evaluation and possesses higher
      reproducibility. The test with nitroglycerin substantially increases its
      diagnostic potential and reproducibility.

PMID- 18038589
TI  - [Clinical picture and treatment of bronchial asthma comorbid with cardiovascular
      diseases].
AB  - AIM: To evaluate prevalence of cardiovascular diseases (CVD) in bronchial asthma
      (BA) patients and effects of CVD on BA course. MATERIAL AND METHODS: Register
      data for 2005 have been analysed for 5104 BA outpatients living in Krasnoyarsk
      city (pulmonary ventilation, ECG, echocardiography, duration of BA, number of
      exacerbations for the last 12 months, number of hospitalizations, disability, BA
      complications, BA and CVD treatment). RESULTS: Combination of BA with CVD was
      observed in 88.3% patients. Severe and moderate BA was in 55 and 44% patients,
      respectively. 64% BA patients were invalids. CVD were diagnosed more often in
      patients with detected BA. CVD were treated without allowances for BA. The latter
      was treated without consideration of its severity and GYNA recommendations.
      CONCLUSION. To control BA, it is necessary to check up pulmonary function
      regularly, to diagnose comorbid cardiovascular diseases early, prescrive adequate
      treatment and teach patients to comply with recommendations.

PMID- 18038590
TI  - [Polymorphic variants of a surfactant protein C gene in patients with chronic
      obstructive pulmonary disease].
AB  - AIM: To investigate effects of polymorphic variants of surfactant protein C gene
      (SFTPC) on the course of the disease in patients with chronic obstructive
      pulmonary disease (COPD). MATERIAL AND METHODS: Sixty COPD patients were examined
      with COPD of stage 0-IV. The following parameters were studied: smoking index
      (SI), bronchial patency, lung pathology by the findings of high resolution
      computed tomography, polymorphisms of SFTPC gene by the data of polymerase chain
      reaction (PCR) followed by mass-spectrometric detection. A trend was found to
      correlation between a polymorphic variant of A138C and COPD severity (p = 0.056).
      A CC genotype occurred more frequently in patients with COPD stages III and IV. A
      significant correlation exists between a polymorphic variant of A186G and the
      disease course severity (p = 0.23). Genotypes AA or AG are more typical for
      patients with COPD stage 0, I and II; GG genotype--stage III and IV. Genotype CC
      SFPTC A138C and genotype GG SFTPC A186G are significantly associated with
      pulmonary emphysema (p = 0.004 and p = 0.01, respectively). CONCLUSION:
      Polymorphic variants of SFTPC affect COPD course.

PMID- 18038591
TI  - [Myxoma of the left atrium: a case report].

PMID- 18038592
TI  - [Prevention of venous thrombosis and pulmonary artery thromboembolism in non
      surgical patients: specification of indications].

PMID- 18038593
TI  - [Clinical implications of coronary stents coated with drugs].

PMID- 18038594
TI  - [HCV-infection and cardiovascular diseases].

PMID- 18038595
TI  - [Cardiac resynchronizing therapy in the treatment of chronic cardiac failure].

PMID- 18038596
TI  - [Neuroleukemia in adult patients with acute lymphoblastic leukemia: problems and
      perspectives. Part 1. Specific features of diagnosis and neurorecurrence risk
      factors].

PMID- 18038597
TI  - [Evidence-based pharmacotherapy and pulmonology: ways of quality achievement].

PMID- 18038598
TI  - [Familial sarcoidosis].
AB  - The paper analyzes cases of familial sarcoidosis that have occurred in the Ryazan
      regional tuberculosis dispensary in the past 10 years. Certain patterns in the
      course of the disease have been revealed in blood relatives.

PMID- 18038599
TI  - [Medical students as an independent tuberculosis-risk group].
AB  - Of fundamental importance is the detection of tuberculosis among its higher risk
      population groups. This applies in full measure to medical students. The rates of
      Mycobacterium tuberculosis infection, its risk, tuberculin sensitivity, and
      incidence were studied in 2499 students from different higher educational
      establishments. During the study years, there was a significant increase in these
      parameters in medical students during study years as compared to humanitarian
      students, which allows medical students to be considered as an independent social
      tuberculosis-risk group.

PMID- 18038600
TI  - [Use of valvular bronchoblocation in the complex treatment of patients with
      disseminated pulmonary tuberculosis complicated by pulmonary hemorrhage].
AB  - The results of treatment are analyzed in 102 patients with disseminated pulmonary
      tuberculosis complicated by pulmonary hemorrhage. The authors have developed and
      clinically tested a procedure for arresting pulmonary hemorrhage by creating
      therapeutic hypoventilation and atelectasis of a lung portion, in which there is
      a source of bleeding, by using valvular bronchoblocation of the draining
      bronchus. The application of valvular bronchoblocation to patients with pulmonary
      bleeding enhances the efficiency of complex treatment and reduces mortality by
      4.9 times and a need for emergency and urgent surgical interventions by 7.4
      times.

PMID- 18038602
TI  - [Hemodynamic features in persons with posttuberculosis pulmonary changes].
AB  - The specific intravascular and central hemodynamic features were studied in 42
      patients with pronounced posttuberculous changes in the lung in comparison to a
      group of healthy individuals without a history of tuberculosis. Along with
      clinical, functional, and electrocardiographic studies, the authors used
      echocardiography. End ventricular and atrial systolic and diastolic areas, end
      left ventricular systolic and diastolic volume, ejection fraction, stroke and
      cardiac indices were determined. Dilation of the right ventricle and right atrium
      and their increased specific contractility were ascertained in patients with
      pronounced posttuberculous changes. At the same time hypertrophy of the right
      ventricular wall was rarely observed. This gives grounds to regard dilatation of
      the right ventricle as an earlier sign of evolving chronic cor pulmonale that its
      hypertrophy. There were no changes in the left ventricle, left atrium, ejection
      fraction, stroke and cardiac indices, which was explained by the absence of
      intoxication and toxic infective action in the persons clinically recovered from
      tuberculosis.

PMID- 18038601
TI  - [Nitric oxide metabolism in the inclusion of N-acetylcysteine into the complex
      therapy of patients with community-acquired pneumonia].
AB  - Thirty-five patients with community-acquired pneumonia were examined. Studies of
      red blood cells and expired air condensate revealed significant nitric oxide
      metabolic disturbances in them. In a group of 17 patients, the use of N
      acetylcysteine in the complex therapy resulted in the normalization of most
      parameters that characterized nitric oxide metabolism (nitrates, nitrites,
      peroxynitrite, NADP-H-diaphorase, and nitrate reductase activity). The positive
      changes were less significant in the control group receiving mucaltin instead of
      N-acetylcysteine. The established regularities in the balance change of nitric
      oxide metabolism in blood and expired air condensate at the height of the disease
      and positive changes during therapy including N-acetylcysteine suggest that
      nitric oxide plays an important role in the pathogenesis of community-acquired
      pneumonia.

PMID- 18038603
TI  - [Immunological correction in progressive pulmonary tuberculosis].
AB  - The authors used their immunological correction method to treat 154 patients with
      progressive pulmonary tuberculosis. Of them, 38 patients received standard
      antituberculosis therapy (Group 1), 39 had additionally paravasal lymphotrophic
      immunological correction (Group 2), and 38 took antituberculous drugs in
      accordance with individual regimens (Group 3), and 39 patients were treated by
      individual regimens during immunological correction (Group 4). After termination
      of the basic course of chemotherapy, clinical cure was achieved in 61.1, 76.3,
      72.2, and 94.7%, respectively (p < 0.05). During the basic course, mortality was
      11.1, 5.3, and 5.5% in the first three groups. By taking into account the
      immunological status of patients with caseous pneumonia, disseminated, and
      multicavernous pulmonary tuberculous lesion, immunological correction is
      indicated early in the basic course of therapy.

PMID- 18038604
TI  - [The specific features of the serum pattern in patients with pulmonary
      tuberculosis].
AB  - The specific features of the serum pattern were studied in 340 tuberculosis
      patients with different forms and phases of a specific process, by using wedge
      dehydration. In patients with tuberculosis, the predominant serum morphological
      type was established to be an ordered one with the radial pattern being preserved
      (50.3%) (r = 0.95); out of the pathological masses, toxic plaques (77.65%) and
      protein zone folds (66.2%) were prevalent (r = 0.98). In patients with
      circumscribe pulmonary tuberculosis and the productive course of the process,
      there was a preponderance of an ordered serum morphological type and indistinct
      markers of intoxication and lung tissue sclerosis. Disseminated tuberculosis with
      decay and complications was marked by a depressive serum morphological type
      [37.6% (r = 0.72)], severe metabolic disturbances, and markers of intoxication
      and lung tissue sclerosis.

PMID- 18038605
TI  - [Organization of early detection of nephrotuberculosis in risk groups].
AB  - The present capacities of early detection of nephrotuberculosis in risk groups
      are considered in detailed. For this, a total of 1150 patients, including 650
      from general health care facilities and 500 from tuberculosis dispensaries, were
      examined. Comprehensive examination patients from risk groups revealed
      nephrotuberculosis in 135 (11.7%) patients. The most patients with
      nephrotuberculosis were identified in the tuberculosis dispensaries (60.7%)
      whereas these amounted to 39.3% in the general health care facilities. The data
      of medical history, renal ultrasonography, and urinalysis for Mycobacterium
      tuberculosis play an important role in the early detection of nephrotuberculosis.
      The leading techniques in detecting patients with nephrotuberculosis in the risk
      groups are currently X-ray and ultrasonographic studies that identify 60.5 and
      55.7% patients, respectively. The developed clinical, laboratory, and
      ultrasonographic studies in the tuberculosis dispensaries and general health care
      facilities considerably enhance the diagnostic capacities of detecting
      nephrotuberculosis.

PMID- 18038606
TI  - [Current methods for correcting the volume of hemithorax after pneumonectomy for
      tuberculosis].

PMID- 18038607
TI  - [Tanatogenesis in patients with caseous pneumonia in relation to sex].
AB  - The purpose of the present investigation was to study the composition of patients
      with caseous pneumonia (CP), its causes, and fetal outcomes in relation to sex. A
      hundred and ninety-eight patients, including 139 males and 59 females, were
      examined. There was a high proportion of socially dysadapted persons particularly
      among males. The females were most needy. For this reason, late tuberculosis with
      complications as CP (83.3%) or CP as an independent nosological entity was
      originally detectable in half of the cases. Low survival rates and small lengths
      of hospital stay were observed. These patients frequently developed specific
      lesions to other organs (lymph nodes (46%, hematogenic dissemination in every
      four, etc.) and nonspecific complications, such as edema of the brain or lung,
      cor pulmonale, etc. In addition to CP, the direct cause of death is other fatal
      complications in half of the patients. The females proved to be more susceptible.

PMID- 18038608
TI  - [Organization of antituberculous care at the municipal level. Section 1.
      Introduction into the course].

PMID- 18038609
TI  - [Pain versus activity and fatigue in adolescents hospitalized because of cancer
      and rheumatoid diseases].
AB  - INTRODUCTION: Chronic disease in adolescence is followed by many negative effects
      of somatic and psychosocial nature. These effects can be observed especially in
      oncological and rheumatologic diseases. This is due not only to the character of
      the disease, its chronic course, but also aggressive treatment. The objective of
      this work was to evaluate relationship between pain experience and sleep, fatigue
      and physical, social and intellectual functioning of teenage patients. MATERIAL
      AND METHODS: 124 adolescents, 14 to 20 years old, hospitalized because of cancer
      and juvenile rheumatoid arthritis participated in the study. Level of experienced
      pain was measured with VAS--Visual Analog Scale and NRS--Numeric Rating Scale.
      Quality of sleep was assessed with Polish version of Melzacks Questionnaire.
      Fatigue and activity were assessed with a questionnaire of our own construction.
      RESULTS: Pain was a significant symptom accompanying rheumatologic and
      oncological disease, although the sources of pain experience were different.
      Significant percentage of participants suffered from sleep disruption and
      activity impairment. An important relationship between increase of pain intensity
      and sleep disruption in oncological patients was found. Significant relationships
      between pain intensity vs. fatigue and also pain intensity vs. functioning were
      identified. CONCLUSIONS: Pain, fatigue and sleep disruption account for important
      factors in rheumatologic and oncological diseases. They also cause decrease in
      physical, social and mental functioning of teenage patients. Results show that
      there is a significant relationship between outcomes of disease, its treatment
      and impact on functioning and developmental course of adolescents. Care delivered
      to those patients must be integrated and involve multidisciplinary factors.

PMID- 18038611
TI  - [Beneficial effects of statins and angiotensin converting enzyme inhibitors on
      aggregability of red blood cells in hypertensive patients].
AB  - This study was designed to investigate changes in aggregability of red blood
      cells of patients with essential hypertension and concomitant
      hypercholesterolemia (total cholesterol level > 5.0 mmol/l) following the use of
      angiotensin converting enzyme inhibitors (ACE-I) along with or without inhibitor
      of reductase HMG-CoA (statin). Under standard pharmacotherapy (beta-receptor
      anatgonist, calcium chanel antagonist, and diuretic) aggregability of RBC in
      hypertensive patients was significantly increased in spite of the treatment.
      However, in patients receiving additionally ACE-I spontaneous aggregation of RBC
      was attenuated. We found that antihypertensive therapy consisting of ACE-I along
      with statin improved erythrocyte aggregation nearly to the level of normotensive
      and normocholesterolemic patients. Interestingly, this improvement of blood
      rheology was observed prior to statin-induced lowering of total cholesterol.

PMID- 18038610
TI  - [Cytoimmunological changes in the bronchoalveolar lavage in asbestos exposure
      patients].
AB  - Bronchoalveolar lavage (BAL) fluid in the group of 19 patients with the confirmed
      exposure to asbestos was investigated. The cytological and immunocytochemical
      methods as well as computer morphometry were used in this study. In the groups
      studied the differences in cell numbers and BAL cell activity were found,
      especially in the monocytes and macrophages group of cells.

PMID- 18038612
TI  - [Pathomechanisms of functional gastroparesis].
AB  - Functional diseases of the stomach include visceral hypersensitivity, gastric
      dysrhythmias, dysfunction of gastric fundus and acommodation, functional diseases
      of antrum and gastroparesis. A common symptom of this diseases is dyspepsia. A
      background of dyspepsia state functional and organic abnormalities of upper
      gastrointestinal tract. The most serious abnormality is gastroparesis. In this
      review we provide an overview of functional gastroparesis focusing on
      postoperative and hormonal related gastric dysfunction.

PMID- 18038613
TI  - Antral gastric motility impairement and autonomic nervous system dysfunction in
      patients with pancreatic cancer (preliminary results).
AB  - The aim of the study was to evaluate the influence of pancreatic carcinoma on
      gastric motility and autonomic system activity in patients before surgery.
      Patients with histologically confirmed pancreatic cancer were studied. Our
      results show that gastric dysrrhythmias are continuously present in patients with
      pancreatic cancer both with and without gastric emptying delay. Antral
      distribution of meal suggests the presence of impaired proximal gastric response
      to meal due to diminished autonomic nervous system function and impaired
      myoelectric gastric activity in patients with pancreatic cancer.

PMID- 18038614
TI  - [Menopausal changes in circadian heart rate variability].
AB  - OBJECTIVES: Presence of cardiovascular symptoms in perimenopausal period is
      suggested to be associated with the decrease of cardiac autonomic nervous system
      (cANS) regulatory function. AIM: Aim of the study was to evaluate whether
      menopause affects circadian heart rate variability (HRV). METHOD: 42 healthy
      women were divided into two equal groups: premenopausal (age 43 +/- 7 years) and
      postmenopausal (age 53 +/- 3 years, 3.25 +/- 1.6 years after the last
      menstruation). Menopausal status was verified by plasma estradiol and FSH
      activities. In both groups the outpatient 24-hrs ECG recordings were carried out.
      The HRV parameters (SDNN, pNN50, r-MSSD, nLF, nHF) were analysed within the day
      time (6 a.m. - 10 p.m.) and the night-time (10 p.m. - 6 a.m.) ECG. RESULTS: Day
      time recordings showed higher SDNN (128 +/- 23 vs. 104 +/- 36, p = 0.01), pNN50
      (18 +/- 8.3 vs. 7 +/- 4.4 p < 0.001), nLF (74 +/- 11 vs. 33 +/- 5 p < 0.01) in
      the premenopausal patients and higher nHF in the postmenopausal women (39 +/- 3.4
      vs. 26 +/- 11, p < 0.01). In the night-time recordings we observed higher pNN50
      (24 +/- 20 vs. 13 +/- 10, p = 0.01) and nLF (66.5 +/- 17 vs. 37 +/- 5.8, p <
      0.01) in the premenopausal patients with nHF higher in the postmenopausal group
      (44 +/- 5.7 vs. 31.4 +/- 17, p < 0.01). In the premenopausal women higher r-MSSD
      and nHF values were observed at the night time (respectively p = 0.03 and p =
      0.04). Simultaneously higher night-time values of pNN50 (p = = 0.03) and nHF (p =
      0.001) were noted in the postmenopausal group. CONCLUSIONS: Lower time HRV
      parameters suggest decreased parasympathetic regulation of the heart. Lower nLF
      indicates impairment of the arterial baroreceptor reflexes, whereas the increase
      of nHF requests further studies.

PMID- 18038615
TI  - [The autonomic nervous system function in benign prostatic hyperplasia].
AB  - BPH is responsible for lower urinary tract symptoms (LUTS). Pathogenesis of
      prostatic overgrowth is multifactorial. It has been suggested that the autonomic
      nervous system (ANS) may also be involved. The aim of the study was to evaluate
      the role of the ANS activity in pathogenesis of BPH. The study was done in 13 men
      with LUTS secondary to BPH. ANS activity was assessed based on heart rate
      variability (HRV) measurement in resting conditions and after simulation with
      deep breathing (DB test) and the tilt test. LUTS (with IPSS scale), quality of
      life, waist-hip ratio and objective measures of benign prostatic hyperplasia
      (BPH), were evaluated. Correlation for LF/HF ratio vs. BPH variables was
      calculated. Results of the study showed sympathetic overactivity and impaired
      parasympathetic response to stimulation in both DB and tilt test.

PMID- 18038616
TI  - Aspirin augments the concentration of endogenous hydrogen sulfide in mouse brain
      and liver.
AB  - Intraperitoneal injections of lysine acetylsalicylate (L-ASA, aspirin) in a dose
      of 10 mg during 5 consecutive days to BALB/c and B10.PL mice increased the
      concentration of endogenous hydrogen sulfide in their livers. The rise of
      hydrogen sulfur levels was shown also in brains of BALB/c females and B10.PL
      males, however in BALB/c male brains there is no statistically significant
      difference. The mechanism of aspirin action on H2S concentration is discussed.

PMID- 18038617
TI  - [Epizootiology of baculoviruses].
AB  - Analysis of published data demonstrated that the process of baculovirus epizootic
      depends on a set of various factors. The efficiency of the host-parasite
      interaction depends on the virus biological activity, multiplicity of infection,
      biological properties and physiological state of the insect, properties of the
      food plants, and environmental factors. Based on the data obtained by highly
      sensitive methods of molecular biology, this review summarizes the discussion of
      the source of viral infection in baculovirus epizootics. These data shed light on
      the mechanisms underlying the development of epizootic, a relatively
      underexplored natural phenomenon.

PMID- 18038618
TI  - [Bacillus cereus is a microbial decomposer of 2,4-dichlorophenol].
AB  - A microorganism degrading 2,4-dichlorophenol isolated from an aeration pond of
      the Baikal Pulp and Paper Mill was identified as Bacillus cereus BIP507 based on
      morphological and physiological characters as well as 16s rDNA sequencing. This
      microorganism proved able to degrade high 2,4-dichlorophenol concentrations (up
      to 560 microM).

PMID- 18038619
TI  - [Effect of phytohormones on plant regeneration in callus culture of Iris ensata
      Thunb].
AB  - The effect of phytohormones on plant regeneration in callus culture of Iris
      ensata Thunb. was studied. 2,4-Dichlorophenoxyacetic acid (2,4-D) proved to be
      the most convenient auxin for the induction and subculturing of morphogenic
      callus. Biogenic calluses were induced from isolated embryos at the wax-ripeness
      stage in MS medium supplemented with 2,4-D (1.0-2.0 mg/l) and kinetin (0.2-0.5
      mg/l). Changes in the medium hormonal composition favor the development of
      adventitious structures. The setting of vegetative bugs took place in the
      presence of 6-benzylaminopurine, while the development of shoots and root
      primordia was observed after 2,4-D replacement with indoleacetic acid (2.0 mg/l).
      The root initiation in regenerating plants required a hormone-free medium. The
      properties of seedling growth from native regenerating I. ensata were studied.
      Analysis of the shoot structure demonstrated that in vitro cultured plants are at
      the juvenile stage.

PMID- 18038620
TI  - [Salicylic acid induces resistance to Septoria nodorum Berk. in wheat].
AB  - The effect of salicylic acid (SA) on oxalate oxidase and peroxidase activities
      and hydrogen peroxide (H2O2) production in leaf cells has been studied in wheat
      of the susceptible cultivar Zhnitsa infected by the fungus Septoria nodorum, a
      pathogen of wheat leaf blotch. The results show that fungal hyphae spread into
      interstices between mesophyll cells and that infected tissues contain H2O2.
      Treatment with SA results in enhanced H2O2 production in mesophyll cells, which
      is due to activation of oxalate oxidase and peroxidase in the cell wall. It is
      proposed that the modulating effect of SA on oxide reductase activities is
      involved in the induction of protective response to fungal infection in wheat
      plants.

PMID- 18038621
TI  - [Patterns of individual growth of gray garden slug Deroceras reticulatum].
AB  - Individual growth of gray garden slug Deroceras reticulatum was studied under
      laboratory conditions in the period from collection to death. The studied
      population demonstrated different patterns of growth. Three groups of slugs were
      recognized: (1) slugs that reached the maximum weight after 4 months of raring,
      after which their weight rapidly decreased (the life span in culture was 6-7
      months); (2) slugs that have not reached the maximum weight until death (the life
      span was 6-7 months); (3) slugs that reached the maximum weight after 7-8 months,
      after which their weight oscillated with a trend to decrease (the life span was
      about 10 months). The obtained data were approximated by the equation of finite
      growth.

PMID- 18038622
TI  - [Influence of precocene II on the sensory system of antennae and mouthparts in
      larvae of the fruit tree tortricid Archips podana Scop. (Lepidoptera:
      Tortricidae)].
AB  - The influence of precocene II, an antijuvenile agent, on morphological characters
      of the chemoreceptor apparatus of antennae and mouthparts was studied in fifth
      instar A. podana larvae. Treatment with different doses of precocene was
      performed at the egg stage. It proved to cause changes in the form and number of
      basiconic sensilla on the maxillary palps and galea and in the size of basiconic
      sensilla on the second and third antennal segments. The results are discussed
      with respect to the influence of precocenes on the insect sensory system and the
      role of the juvenile hormone in regulation of its development.

PMID- 18038623
TI  - [Study of protein metabolism of herring gulls (Larus argentatus Pontop.) infected
      by trematode Himasthla larina (Trematoda: Echinostomatidae)].
AB  - The values and dynamics of some indices of protein metabolism were studied in
      herring gulls Larus argentatus infected with trematode Himasthla larina in
      natural populations and in experiment. These indices were compared in infected
      and uninfected birds. Trematode infection considerably affected host protein
      metabolism irrespective of the age; however, the changes were more pronounced in
      nestlings. Increased concentration of gamma-globulins, modified albumin, and
      circulating immune complexes was observed in plasma of infected herring gulls.
      The experiments demonstrated the most significant changes in protein metabolism
      of herring gulls 8-11 days after infection with trematode H. larina.

PMID- 18038624
TI  - [Effect of intrahippocampal kainic acid on the behavior of rats and functional
      state of mitochondria in brain structures].
AB  - Cognitive processes and functional state of mitochondria in brain structures of
      Wistar rats were studied after intrahippocampal injection of kainic acid, an
      agonist of glutamate receptors. A single administration of 0.25 microg kainic
      acid into the dorsal part of the left and right hippocampi affected task
      retrieval and decreased inhibition of unrewarded responses. The injection of 0.75
      microg kainic acid induced recurrent seizures and completely disorganized animal
      behavior. The functional state of mitochondria, as an important marker of
      excitotoxicity, was studied after intrahippocampal injections of kainic acid in
      the same doses. Kainic acid at 0.25 microg proved to activate the oxidative
      phosphorylation in hippocampal mitochondria. A higher (epileptogenic) dose of
      kainic acid inhibited mitochondrial respiration in the frontal cortex, but had an
      insignificant effect on mitochondrial respiration in the hippocampus. The
      disturbed interaction between the hippocampal system and frontal cortex after
      kainic acid administration can be the main factor of the revealed cognitive
      dysfunctions.

PMID- 18038625
TI  - [Comparative analysis of analgesic activities of dermorphin, [DPro6]-dermorphin,
      and their C-terminal tripeptides].
AB  - Analgesic activities of dermorphin (DM), [DPro6]-DM, and their C-terminal
      tripeptides were comparatively studied. Analgesic activity was evaluated in tail
      flick, hot plate, tail pinch, formalin, and acetic acid writhing tests describing
      different levels of organization of pain sensitivity. Intraperitoneal
      administration of the peptides decreased the pain threshold in all these tests.
      The C-terminal tripeptides DM(5-7) and [DPro6]-DM(5-7) demonstrated analgesics
      activity comparable or sometimes higher than that of the full-length molecules.
      The effect of DM, [DPro6]-DM, and C-terminals fragments DM(5-7) and [DPro6]-DM(5
      7) decreased after co-administration with naloxone, which points to the opioid
      nature of analgesic activity of the peptides.

PMID- 18038626
TI  - [Effect of antioxidant beta-(4-hydroxy-3,5-ditertbutylphenyl) propionic acid
      (phenosan) on the development of malignant neoplasms].
AB  - The effect of different doses of synthetic antioxidant beta-(4-hydroxy-3,5
      ditertbutylphenyl)propionic acid (phenosan) on the development of spontaneous
      leukemia in AKR mice was studied. The drug efficiency was determined from the
      survival curves, animal life spans, and the incidence of leukemia. Phenosan
      exhibited a pronounced antitumor activity at therapeutic (10(-4) mol/kg, 4
      administrations) and ultra-low (10(-14) mol/kg, 4 administrations) doses. The
      dose of 10(-4) mol/kg proved most efficient to increase the life span of the
      shortlived subpopulation, while the dose of 10(-14) mol/kg increased the life
      span of the long-lived subpopulation. The ultra-low dose of the drug seems
      promising as a prophylactic agent.

PMID- 18038627
TI  - [Soil microarthropods and macrofauna in monsoon tropical forests of Cat Tien and
      Bi Dup-Nui Ba National Parks, Southern Vietnam].
AB  - The abundance, biomass, vertical distribution, and taxonomic composition of soil
      invertebrates (springtails, macrofauna, and termites) were studied in forest
      formations differing in edaphic and climatic conditions: lowland forests
      dominated by Lagerstroeomia spp. or Dipterocarpus spp. in the Cat Tien National
      Park and in a mountain pine (Pinus kesiya) forest on the Da Lat Plateau, southern
      Vietnam. In the lowland forests, springtails had a relatively low density (10000
      12000 ind./m2), but their diversity was high (41-43 species in each forest). The
      density of large soil invertebrates (without ants and termites) reached 500-700
      ind./m2 at a biomass of approximately 30 g/m2 (with earthworms accounting for up
      to 230 ind./m2 and 19-28 g/m2). Among termites, species of the genera Macrotermes
      and Odontotermes were dominant. Their total biomass in some areas exceeded 15-20
      g/m2. In the mountain pine forest, the total biomass of soil macrofauna was
      approximately 11 g/m2, the abundance and diversity of springtails were low (7500
      ind./m2, 28 species), and wood-destroying species of the genera Schedorhinotermes
      sp. and Coptotermes sp. dominated among termites.

PMID- 18038628
TI  - [Species structure and dynamics of bat communities (Chiroptera: Vespertilionidae)
      hibernating in artificial caves of Samara Luka].
AB  - Long-term data on the composition and absolute and relative abundance of eight
      bat species hibernating in artificial caves of Samara Luka are considered. About
      13,000 hibernating individuals are annually accounted there. The relative
      abundance of the species decreased in the following order: Myotis brandtii (35%),
      Plecotus auritus (20%), M. daubentonii (13%), M. mystacinus (13%), Eptesicus
      nilssonii (8%), M. dasycneme (8%), and M. nattereri (2%). Singular E. serotinus
      were recorded not every year. The number of hibernating animals in pits was
      proportional to their size and the number of shelters. Bats used previously
      chosen shelters and were never found in adjacent caves. The maximum species
      diversity (H') and evenness (E) were observed in bat communities in medium-sized
      caves. One of the main factors of increasing abundance of hibernating bats in
      abandoned pits is their gradual colonization by the animals.

PMID- 18038629
TI  - [Transformation of soil invertebrate complex after surface fires of different
      intensity].
AB  - The effect of surface fires of different intensity on soil invertebrates was
      evaluated in central taiga Scotch pine forests in the Yenisey Region of Siberia.
      In the period of 4-5 years, the abundance and ecological and trophic structure of
      sandy podzol population was almost completely restored after surface fires of
      medium and low intensity. The recovery process was decelerated after high
      intensity fires.

PMID- 18038630
TI  - [Comparative study of hemostatic properties of the complex and mixture of high
      molecular weight heparin and adenosine triphosphate].
AB  - Anticoagulant and nonenzymatic fibrinolytic activities increased in blood plasma
      of 6-7-month-old rats after repeated intramuscular administration of the heparin
      adenosine triphosphate complex (G-ATP). The mixture of heparin and ATP had no
      fibrin depolymerizing activity in vitro. Repeated intramuscular administration of
      the mixture had anticoagulant effect although it was 1.5-1.6 times less
      pronounced compared to the complex. A higher anticoagulant and fibrinolytic
      efficiency of the G-ATP complex compared to the mixture is concluded.

PMID- 18038631
TI  - [Vertical structure of bacterial communities in peats of the Yakhroma River
      floodplain].
AB  - The abundance and taxonomic structure of soil bacterial communities have been
      studied in different geomorphological parts of the Yakhroma floodplain. It has
      been found that the numbers of bacteria reach a peak in calcareous peat soil
      under forest near the floodplain terrace, decreasing to a minimum in soddy
      alluvial soil near the riverbed. All soils are characterized by the presence of
      different ecological-trophic bacterial groups capable of peat destruction.
      Seasonal dynamics of the structure of bacterial communities and, in some soil
      types, its spatial dynamics accounted for by changes in the botanical structure
      of peat across its profile have been revealed. All peat soils in the floodplain
      have high contents of organic matter and neutral pH and, therefore, are favorable
      biotopes for the development of saprotrophic bacteria. This, in turn, largely
      accounts for high productivity and stability of this agroecosystem as a whole.

PMID- 18038632
TI  - [Annual production of moss layer in dark coniferous forests of Ket-Chulym Forest
      District (by the example of Moss Hylocomium splendens)].
AB  - The biological production of the moss layer was analyzed in dark coniferous
      stands in progressive succession in the southern taiga in West Siberia. The rate
      of organic matter production by mosses changed from 15-22.2 g/(m2 y) in 50-90
      year-old fir forests to 51.6 g/(m2 y) in 170-year-old mixed Siberian pine-spruce
      fir stands. In forest phytocenosis that were formed with species replacement
      (after cuttings with understory clearing), the annual moss production (net
      primary production) ranged from 2.8 to 20.6 g/(m2 y). The annual moss cover
      production amounted to 35-36% of the moss photosynthetic biomass irrespective of
      the type of native stand progressive succession and the stand age.

PMID- 18038633
TI  - [Motor activity of infusoria: fundamental and applied aspects].
AB  - The article considers morpho-functional organization of the cilia, locomotor
      organelle of the infusoria, and demonstrates the complicity of locomotor behavior
      of these protista. The problem of control of locomotion of infusoria is whole
      organism in discussed; and conclusion is drawn that system of control of
      movements could be multilevel and include receptor, afferent, central, efferent
      and effector units. In this context the macronucleus, could act as a central
      integrator and coordinator of the locomotor behavior being closely connected with
      periphery by dynamic elements of cytoskeleton. The eradication of infusoria
      parasitizing in humans and animals by interrupting of locomotion of the protista
      is also discussed.

PMID- 18038634
TI  - [Evolutonary modifications of molecular structure of ATP-synthase gamma-subunit].
AB  - The ATP-synthase gamma-subunit (FoF1) belongs to the rotor part of this
      oligomeric complex. Catalytic hydrolysis of adenosine triphosphate (ATP) is
      accompanied by rotation of gamma-polypeptide inside the sphere formed by six
      subunits (alphabeta)3 of the enzyme. The gamma-subunit regulates ATPase and ATP
      synthase activities of the FoF1. In the present work, evolutionary and reverse
      changes of this regulatory polypeptide and their effect on properties of the
      enzyme are studied. It is suggested that elongation of the gamma-subunit globular
      part had resulted from the atpC intragene duplication in the process of adaptive
      evolution. The evolved fragment participates in light regulation of the
      chloroplast ATP-synthase.

PMID- 18038635
TI  - [Characteristics of proteinase digestive function in invertebrates--inhabitants
      of cold seas].
AB  - Digestive proteinases of various taxa of invertebrates of the Northern seas have
      been studied: crustaceans Paralithodes camtchaticus, Pandalus borealis; molluscs
      Chlamys islandicus, Buccinum undatum, Serripes groenlandicus, and echinoderms
      Strongylocentrotus droebachiensis, Cucumaria frondosa, Asterias rubens, and
      Grossaster papposus. The presence of two proteolytic activity peaks in the acid
      (pH 2.5-3.5) and low alkaline zones (pH 7.5-8.5) and a similar proteinase
      spectrum have been revealed in digestive organs of the studied animals. The
      proteolytic activity in digestive organs of the Barents Sea invertebrates exceeds
      significantly that of terrestrial homoiothermal animals, which seems to be an
      extensive compensation for poor differentiation of the digestive system and for
      low substrate specificity of the enzymes as well as for cold conditions of the
      habitat. The principal qualitative difference between vertebrates and
      invertebrates consists in that the latter have no pepsin activity, but do have
      the cathepsin activity that is absent in vertebrate digestive organs.
      Contribution to the acid proteolysis is made by lysosomal cathepsins, rather than
      by pepsins. Activity in the alkaline and neutral pH zones is provided by serine
      proteinases. In digestive cavities of invertebrates, hydrolysis of proteins and
      mechanical processing of food occur only in the low alkaline zone, whereas acid
      proteolysis has intracellular lysosomal localization.

PMID- 18038636
TI  - [Activities of proteinases in invertebrate animals--potential objects of fish
      nutrition. Effects of temperature, pH, and heavy metals].
AB  - Differences in the degree of separate and combined effects of temperature, pH,
      and heavy metals (zinc, copper) on the trypsin- and chymotrypsin-like proteinase
      activities have been established in the whole body of some invertebrate animals -
      potential objects of fish nutrition: pond snail Lymnaeae stagnalis, orb snail
      Planorbis purpura, zebra mussel Dreissena polymorpha, oligochaetae Tubifex sp.
      and Lumbriculus sp. in total, chironomid larvae Chironimus sp. and Ch. riparus,
      as well as crustacean zooplankton. It has been shown that enzymes of the
      potential victim at a low temperature can compensate low activity of intestinal
      proteinases of fish bentho- and planktophages.

PMID- 18038637
TI  - [Comparative study of bile-acid composition in the bile of the European vendace
      Coregonus albula L. and whitefish Coregonus lavaretus L. under conditions of
      technogenic water pollution].
AB  - Changes of the bile acid composition were studied in bile of the vendace
      Coregonus albula L. and the whitefish Coregonus lavaretus L. under effect of
      sewers of an ore mining and processing plant, the main pollutin agents of the
      sewers being heavy metals. The revealed variability of the bile acid composition
      indicates different species-related sensitivity to the studied pollutants as well
      as a lower resistance of males as compared with females to this type of
      pollution. Mechanisms of effects of industrial sewers on the bile formation
      processes and a possibility of using parameters of the steroid lipid metabolism
      at evaluation of the state of water ecosystems are discussed.

PMID- 18038638
TI  - [Changes of physiological and biochemical characteristics of rat erythrocytes
      after blood loss].
AB  - In experiments of Wistar male rats, changes are studied of erythrocyte
      hematological, biochemical (activitities of transport ATPases), and rheological
      properties (capability for aggregation and deformability) 7 days after
      bloodletting of 12-15 % of the total blood mass. It has been shown that alongside
      with an elevation of erythrocyte volume and of the number of immature cells -
      reticulocytes, there was a statistically significant increase of Na,K-ATPase and
      Ca-ATPase activities in the whole erythrocytes and their membrane preparations -
      ghosts, the increment of activity in the case of Na,K-ATPase being essentially
      higher in the whole cells. This indicates the appearance of an enzyme activator
      inside the erythrocytes. There are also revealed a decrease of firmness of
      erythrocyte aggregates, a deceleration of spontaneous aggregation, and an
      increase of index of erythrocyte deformability. The conclusion is made that
      changes of erythrocyte rheological properties are interconnected with changes of
      the Na,K-ATPase activity and are directed to optimization of blood circulation in
      large vessels and capillary network.

PMID- 18038639
TI  - [Comparative study of the "membrane reserve" of blood cells of reptiles and
      mammals].
AB  - Based on the method of hypoosmotic loads, the value of membrane reserve and its
      use by blood cells of reptiles and mammals have been studied. It has been shown
      that lymphocytes of the both animal species have the highest reserve of
      plasmalemma, while frog heterophils - the lowest one. A significantly lower part
      of the membrane reserve participates in formation of phagosomes by mammalian
      neutrophils as compared with amphibian erythrocytes.

PMID- 18038640
TI  - [Morphological manifestations of astrocyte local functional activation produced
      by a short-term total brain ischemia].
AB  - The goal of this work was to study changes structural and cytochemical
      organization of rat hippocampus activated astrocytes after a brief total brain
      ischemia. By methods of immunocytochemical determination of proteins of
      intermediate filaments, in was established that 7 days after the ischemia the
      functional activation of dorsal hippocampus astrocytes is morphologically
      manifested both as changes of size and shape of the cells and their processes and
      as accumulation of the intermediate filament proteins -GFAP and nestin. Two
      populations of the activated astrocytes are formed - more dispersed GFAP-positive
      astrocytes and nestin-positive astrocytes located predominantly in the area of
      massive death of nerve cells. The obtained data allow suggesting that the
      postischemic activation of astrocytes is accompanied by their acquistition of
      properties characteristic of immature cells of the nervous tissue; however, the
      absence of morphological signs of dedifferentiation does not permit these cells
      to be considered responsible for reparational neurogenesis in hippocampus.

PMID- 18038641
TI  - [Effect of swinging on EEG of rats of juvenile age in the wakefulness state].
AB  - Simultaneous recording of the EEG activity of superficial cortical and deep
      (caudate nucleus, dorsal hippocampus, anterior hypothalamus) brain parts has been
      performed for the first time after a 2-h swinging of frequency of 0.2 Hz in
      Wistar rats of juvenile age. Swinging was produced on a 4-bar parallel swing.
      Using a Neuron-Spectr electroencephalograph and a Diana program, normalized power
      spectra of wave EEG components, synchronization coefficients, and coefficients of
      cross-correlation between bioelectrical potentials of various brain structures
      were determined. After a 2-h swinging, the mean value of normalized power of slow
      waves of delta-diapason in hypothalamus and hippocampus was found to increase
      statistically significantly, while normalized power of fast waves of alpha- and
      beta1-diapasons in hippocampus decreased (p < 0.05). A statistically significant
      increase of synchronization coefficient was observed in hypothalamus and
      hippocampus. Changes of coefficients of cross-correlation between hypothalamus
      and hippocampus and other brain strictures were of the oppositely directed,
      individual character. In the parietal occipital brain cortex and in caudate
      nucleus, the changes of the EEG spectral composition also were of individual
      character. The obtained results on the whole correspond to data about an
      enhancement of the EEG low-frequency rhythms at swinging and agree with the
      resonance hypothesis of motion sickness.

PMID- 18038642
TI  - [The number of active Purkinje cells in the microelectrod track as an indicator
      of maturity of the cerebellum motor function in precocial- and altricial-born
      animals].
AB  - In experiments on 5 age groups of anesthetized guinea pigs (from newborns to 4
      weeks of postnatal ontogenesis), activity of cerebellum Purkinje cells (PC) (IV
      VII lobules of cerebellar vermis) was studied in the single track of
      microelectrode passing through cell layers. It has been shown that as early as
      several hours after birth, in the superficial layer of cerebellar cortex, there
      are recorded occasional background-active, but functionally mature PC represented
      by simple and complex spikes and accordingly reflecting synaptic PC activation by
      afferent inputs of mossy and climbing fibers. The functional manifestation of the
      guinea pig motor behavior at this period of ontogenesis is act of their standing.
      At this period of ontogenesis, in the newborn and one-day old guinea pigs, from 1
      to rarely 11 active PC are recorded, on average, in the single microelectrode
      track. At the one-week age, the highest number active PC in the track somewhat
      increases, predominantly at the expense of the mean from the total number of the
      cells in the track. In the 2-week old guinea pigs the mean number of active PC in
      the track somewhat falls, while in the 4-week old and adult animals exceeds
      again, although slightly of the maximal number of PC in the track of newborn
      animals. The relatively high number of active PC at the very initial period of
      postnatal ontogenesis can indicate importance of motor function in the congenital
      food-procuring reflex.

PMID- 18038643
TI  - [Retina mediators in fresh-water mollusc Lymnaeae stagnalis].
AB  - Retrograde staining of the Lymnaeae stagnalis retina with neurobiotin has shown
      that most photoreceptor cells send axons to optic nerve without intermediate
      contacts. A part of these photoreceptors have immunireactivity to glutamate that
      possibly provides synaptic transmission of visual signal to central neurons.
      Other photoreceptors stained through optic nerve seem to have different
      transmitter systems. In some retina cell, but not in optic nerve fibers,
      immunoreactivity to pigment-dispersing hormone has been revealed. In tissues
      surrounding the eye cup numerous serotonin-containing fibers are present, a part
      of them penetrating the retina basal layer. Some of them belong to central
      neurons responsible for efferent innervation of the pond snail eye. It is
      suggested that the serotoninergic innervation as well as the cell containing the
      pigment-dispersing hormone are included in the mechanism of regulation of light
      sensitivity of the mollusc eye.

PMID- 18038644
TI  - [Neutrophin NGF protects glial cells, but not stretch receptor neurons of the
      crayfish Astacus astacus from photooxidative stress].

PMID- 18038645
TI  - [Mechanisms of adaptive regulation of early development of Anuran amphibians
      dwelling the anthropogenically polluted water bodies].
AB  - Comparison of the gastrulation in three Anuran species has shown the possibility
      of evolution of earlier morphogenesis directed to adaption to such new
      environmental factor as anthropogenic pollution of water bodies. Changing
      proportion of variability and correlation of the developing embryonic structures
      causes changes in the character of morphogenetic processes to the point of
      discoordinated development and formation of heterochronies and/or increased death
      rate. In the studied amphibian species, the increase of the concordent
      development in different populations resulted either from increased general
      correlation of morphogenesis or from the emergence of a group of traits with more
      interdependent development. Mechanisms of early development regulation comply
      with a single scheme, which indicates the nonspecificity of early embryogenesis
      reaction based on epigenetic regulation mechanisms.

PMID- 18038646
TI  - On the power of some binomial modifications of the Bonferroni multiple test.
AB  - Widely used in testing statistical hypotheses, the Bonferroni multiple test has a
      rather low power that entails a high risk to accept falsely the overall null
      hypothesis and therefore to not detect really existing effects. We suggest that
      when the partial test statistics are statistically independent, it is possible to
      reduce this risk by using binomial modifications of the Bonferroni test. Instead
      of rejecting the null hypothesis when at least one of n partial null hypotheses
      is rejected at a very high level of significance (say, 0.005 in the case of n =
      10), as it is prescribed by the Bonferroni test, the binomial tests recommend to
      reject the null hypothesis when at least k partial null hypotheses (say, k =
      [n/2]) are rejected at much lower level (up to 30-50%). We show that the power of
      such binomial tests is essentially higher as compared with the power of the
      original Bonferroni and some modified Bonferroni tests. In addition, such an
      approach allows us to combine tests for which the results are known only for a
      fixed significance level. The paper contains tables and a computer program which
      allow to determine (retrieve from a table or to compute) the necessary binomial
      test parameters, i.e. either the partial significance level (when k is fixed) or
      the value of k (when the partial significance level is fixed).

PMID- 18038647
TI  - [The response of the genomic pattern of transposable elements TE412 to
      quantitative trait selection in Drosophila melanogaster].
AB  - The results of four selection-genetic experiments aimed at the genetic
      transformation of the quantitative trait controlled by the radius incompletus
      gene of Drosophila melanogaster are given. Directional (s+) and (s-)-selection
      was conducted. At the of end all the experiments, in (s+)-selection the radial
      vein of the wing was restored to the wild phenotype, in (s-)-selection complete
      elimination of the radial vein took place. In four variants of selection,
      different TE412 pattern was formed under (s+)-selection and (s-)-selection in
      final generations. Correlation coefficient between (s+)-selection and (s-)
      selection is -0.576, p < 0.001. At the same time, correlation coefficient between
      two independent replications of (s+)-selection is 0.912, p < 0.001, and of (s-)
      selection, 0.946, p < 0.001. Thus, the availability of associated response to the
      selection of a quantitative trait and to the TE412 pattern is experimentally
      proved. Three hypotheses of the possible TE behaviour under selection are
      discussed.

PMID- 18038648
TI  - [The microbial loop in the planktonic communities in lakes with various trophic
      status].
AB  - The structure of planktic trophic chains was studied in eight lakes of European
      Russia and five lakes in Central Asia. The lakes differed in the level of
      productivity, morphometric parameters, and the type of agitation and
      mineralization. It is found that the microbial loop of picophototrophic
      organisms, bacteria, heterotrophic flagellates, infusoria, and viruses
      constitutes 12.3-64.7% of the total plankton biomass. Positive correlation
      between the biomass of microbial community and the primary production of
      phytoplankton is observed, whereas no relation is revealed between the share of
      microorganisms in the plankton biomass and the trophic status of the water body.
      The presence of a great number of cladocerans decreased the role of the microbial
      loop in the structural organization of the planktic community. Heterotrophic
      flagellates consuming 3-81% of daily bacterial production were the principal
      cause of bacteria elimination only in some of the studied water bodies.

PMID- 18038650
TI  - [The comparative aspects of spatial ecology of lizards exemplified by the toad
      headed lizards (Reptilia, Agamidae, Phrynocephalus)].
AB  - The possibility of analysis of phylogenetic parameters of the spatial
      distribution of populations is discussed by an example of the agamid toad-headed
      lizards (Phrynocephalus). Summarizing both original and published data on the
      individual home ranges and the relocation of individuals of 30 populations from
      12 species showed that differentiation of the type of spatial distribution is
      weak in toad-headed lizards. This observation confirms the idea that this clade
      of agamids is phylogenetically young and relatively recently radiated. At the
      interspecific level, positive correlation between home range size and body size
      was observed in the studied group. Such spatial parameters, shared by all toad
      headed lizards, as relatively large size and weakly structured individual home
      ranges can be explained by the peculiarities of their reproduction features and
      their foraging mode. The individual type of space-usage in toad-headed does not
      fit the traditional scheme dividing all the lizards into the territorial Iguania
      and the nonterritorial Autarchoglossa.

PMID- 18038649
TI  - [Interrelation between the flower structure and composition of the pollinator
      groups for Dipsacaceae and Asteraceae with externally similar anthodia].
AB  - The competitive relations between members of phylogenetically distant plant
      families Asteraceae (Centaurea and Cirsium) and Dipsacaceae (Knautia and Succisa)
      with purple anthodia, sharing a common wide range of pollen vectors and competing
      for them, were studied. The composition of pollen vectors is somewhat different
      in different plant species. Only bumble-bees, the most effective pollinators,
      were observed visiting every studied plants species. Syrphidae flies,
      Lepidoptera, Coleoptera, and some other insects were also observed in different
      proportions. The principal importance for pollination of the corolla tube size,
      correlating with the size of insect mouthparts, and the additional importance of
      particular traits of the inflorescence are confirmed. Convergent similarity of
      the aspect of anthodia in two species of different families is shown to be based
      on different structural and functional features. Insect pollinators are the
      factor of anthodia convergence. The plant species studied are divided into the
      following three groups, according to the proportion of bumble-bees among pollen
      vectors and to the range of species-specific pollinators; species coadapted to
      one pollinator taxon; species coadapted to two or three pollinator taxa; and
      species coadapted to many pollinator taxa. Asteraceae species in general (with
      the exception for Cirsium arvense) are characterized by constant contacts with a
      narrower range of pollinators than Dipsacaceae species (and Cirsium arvense),
      characterized by wider range of pollinators. Among flowering plants with similar
      anthodia, the tighter structural coadaptations of Asteraceae with their effective
      pollinators provide their greater competitive ability as compared to Dipsacaceae.

PMID- 18038651
TI  - [Formation of immune proteasomes and development of the immune system in
      mammalian ontogenesis].
AB  - Current concepts of the structure of immune proteasomes and their role in immune
      response have been considered. The main attention has been paid to the formation
      of immune proteasomes in secondary lymphoid and nonlymphoid organs during
      ontogenesis of mammals. The causes of ineffective formation of immune system in
      early postnatal development have been discussed.

PMID- 18038652
TI  - [Molecular-genetic mechanisms of the effect of developmental hormones in
      insects].
AB  - A review of the available data on molecular mechanisms underlying the regulation
      of gene expression by the developmental hormone ecdysone and juvenile hormone.
      Heterodimer ESP/USP is the main ecdysone receptor in D. melanogaster. Structures
      similar to ESP/USP were found in other insects. The information about molecular
      genetic mechanisms of the effect of juvenoids is less definite. It has been
      proposed that the juvenile hormone in insects is a modulator of the ecdysone
      effect.

PMID- 18038653
TI  - [Proliferative zones in the brain of the Amur sturgeon fry. Interactions with
      neuromeres and migration of secondary matrix zones].
AB  - Neurogenesis in the forebrain region was studied in the Amur sturgeon Acipenser
      schrenki fry using immunocytochemical marking of the proliferative nuclear
      antigen. The brain zones with high proliferative activities were located at the
      brain ventricle surface facing the periventricular cavity. In addition to the
      periventricular zone of primary proliferation, several secondary proliferative
      zones were found in the forebrain region of the Amur sturgeon.

PMID- 18038654
TI  - [Spatial-temporal dynamics of morphogenetic blastoderm potencies in early
      embryogenesis of the loach].
AB  - The degree of differentiation of axial structures (notochord, neuroectoderm, and
      somites) in 24-hour explants (a total of 380) of the loach embryonic blastoderm
      was determined on histological sections according to a developed scale of
      estimates. Before the beginning of epiboly, axial structures were formed only
      from fragments of the dorsal sector of the blastoderm marginal zone. Its other
      sectors acquired the capacity of forming axial structure only with the beginning
      of epiboly, as the germ ring was formed in the marginal zone, unlike the cells
      outside the germ ring. The degree of differentiation of axial structures in the
      dorsal sector of marginal zone increased reliably with the appearance of
      embryonic shield, i.e. area of the convergence of cell flows. Here, statistically
      significant regional differences in morphogenetic potencies of the marginal zone
      first appeared, which corresponded to the differences in prospective significance
      of its materials; notochord and neuroectoderm better differentiate from the
      dorsal sector material, while somites better differentiate from the ventral
      sector material. Thus, distribution of morphogenetic potencies reflects precisely
      the spatial-temporal dynamics of collective movement of the blastoderm cells
      during the normal course of morphogenesis.

PMID- 18038655
TI  - [Development of the model of the cell cycle synchronization in early embryos of
      Danio rerio (Teleostei)].
AB  - An attempt was undertaken to develop a model system based on artificial cell
      cycle synchronization by means of reversible mitosis blocking in zebrafish
      embryos for studying the role of cell cycle synchrony in embryogenesis.
      Dechorionized and intact embryos at the stages of 512-cell blastula and 75%
      epiboly were treated with nocodazole and then washed within several times of
      exposure. When working on dechorionized embryos, we succeeded to obtain complete
      block mitosis in the presence of low nocodazole concentrations: 0.5-1.0
      microg/ml. Block of mitosis was relieved in all experimental series within a
      certain time after the beginning of washing. This inertia depended on both
      nocodazole concentration and duration of treatment. The nocodazole elimination
      was significantly accelerated only after five (or more) changes of washing medium
      containing DMSO. As a result, the conditions were established for obtaining a
      parasynchronous cell population in the zebrafish gastrulas with a peak of mitosis
      up to 17.2%.

PMID- 18038656
TI  - [Detection of carotenoids in the vitreous body of the human eye during prenatal
      development].
AB  - Carotenoids were found for the first time in the vitreous body of human eye
      during the fetal period from week 15 until week 28. Their maximum content was
      timed to week 16-22. No carotenoids were found the vitreous body of 31-week
      fetuses, as well as adult humans, which corresponds to the published data. It was
      shown using HPLC that chromatographic characteristics of these carotenoids
      correspond to those of lutein and zeaxanthin, characteristic pigments of the
      retinal yellow macula.

PMID- 18038657
TI  - [Ultraweak emissions of the developing Xenopus laevis eggs and embryos].
AB  - We measured ultraweak emissions of the Xenopus laevis eggs and embryos during
      normal development and under the influence of stress factors in a spectral range
      of 250 to 800 nm using a photomultiplier. The registered emissions were analyzed
      by several basic characteristics: mean intensity, histograms, kurtosis, linear
      trends, and Fourier spectra. We followed relationships between these parameters
      and developmental stage, as well as the number of individuals in optic contact
      with each other. The ultraweak emissions did not differ from the background at
      all developmental stages according to the mean intensity. But Fourier analysis
      revealed the reliable presence of a number of spectral lines of ultraweak
      emission, predominantly in the ranges of 10-20 and 30-40 Hz, in the embryos at
      developmental stages 2 to 11. The intensity of ultraweak emissions reliably
      decreased within the first 10 min after egg activation and fertilization, as well
      as in the case of optic interaction between groups of embryos. Sharp cooling,
      increase in osmotic medium pressure, and transfer in a Ca(2+)- and Mg(2+)-free
      medium induced a short term (approximately 1-5 min) increase in the mean
      intensity of ultraweak emission. We studied specific features of ultraweak
      emissions from different parts of the embryo. The intensity of emission from the
      animal part of early blastula exceeded those from the vegetal area and entire
      embryo. Separated fragments of the lateral ectoderm at the neurula stage had
      higher mean intensities of ultraweak emission than intact embryos at the same
      developmental stages.

PMID- 18038658
TI  - [Changes in EEG coherence during tests for nonverbal (figurative) creativity].

PMID- 18038659
TI  - [Changes in the power and coherence spectra of the EEG rhythmic components during
      solution of a verbal creative task of overcoming a stereotype].

PMID- 18038660
TI  - [Mismatch negativity as a characteristic of the distinguishing locating capacity
      of the human auditory system].

PMID- 18038661
TI  - [The subjective auditory space of epileptic patients with lesions in both the
      temporal cortical area and the hippocampus].

PMID- 18038662
TI  - [EEG markers of the disturbed systemic brain activity in hypoxia].

PMID- 18038663
TI  - [Complex of rehabilitation measures for compensation of psychoemotional stress
      consequences].

PMID- 18038664
TI  - [Differential sphygmogram of the radial artery in the evaluation of the heart
      pumping function].

PMID- 18038665
TI  - [Quick adaptation of the myocardium and autonomic nervous regulation of the
      cardiac rhythm in 10- to 11-year-old children operating a computer].

PMID- 18038666
TI  - [Using spiroarteriocardiorhythmography as a functional test for estimating the
      state of the cardiorespiratory system in adults and children].

PMID- 18038667
TI  - [Dynamic oscillatory circuit of the capillary hemodynamic regulation].

PMID- 18038668
TI  - [Effects of various hyperbaric gas mixtures on metabolic parameters of human
      blood].

PMID- 18038669
TI  - [Correction of venous congestion in abdominal organs under antiorthostatic
      conditions].

PMID- 18038670
TI  - [Age-dependent development of muscular activity energetics: summary of a 30-year
      study. III. Effect of endogenous and exogenous factors on development of the
      skeletal muscle energetics].

PMID- 18038671
TI  - [Relationships of inflammatory activity with biochemical parameters of the blood
      and sympathovagal balance in young athletes].

PMID- 18038672
TI  - [Physiological role of the functions of pattern recognition receptors in
      immunology].

PMID- 18038673
TI  - [Nontraditional approaches to biomedical screening (multifactorial diseases).
      Communication I].

PMID- 18038674
TI  - [The possible use of new technologies for treating some diseases at the atomic
      molecular level].

PMID- 18038675
TI  - [Aleksei Nikolaevich Bakh: a great scientist and founder of domestic
      biochemistry].

PMID- 18038676
TI  - [Initiation and inhibition of free-radical processes in biochemical peroxidase
      systems: a review].
AB  - The role of complexes containing oxygen or peroxide in monooxygenase systems and
      models thereof, as well as in peroxidase- and quasi-peroxidase-catalyzed
      processes, has been reviewed. Pathways of conversion of these intermediate
      complexes involving single-electron (radical) and two-electron (heterolytic)
      mechanisms are dealt with. Coupled peroxidase-catalyzed oxidation of aromatic
      amines and phenols is analyzed; inhibition and activation of peroxidase-catalyzed
      reactions are characterized quantitatively. Oxidation of chromogenic substrates
      (ABTS, OPD, and TMB) in the presence of phenolic inhibitors or polydisulfides of
      substituted phenols is characterized by inhibition constants (Ki, micromol).
      Activation of peroxidase-catalyzed oxidation of the same substrates is
      characterized by the degree (coefficient) of activation (alpha, M(-1)), which was
      determined for 2-aminothiazole, melamine, tetrazole, and its 5-substituted
      derivatives. Examples of applied use of peroxidase-catalyzed enzyme and model
      systems are given (oxidation of organic compounds, chemical analysis, enzyme
      immunoassay, tests for antioxidant activity of biological fluids).

PMID- 18038677
TI  - [Reactive oxygen species and the strategy of the antioxidant defense in fungi: a
      review].
AB  - The level of reactive oxygen species (ROS) in the cell regulates the growth and
      differentiation of the fungal organism. This review considers the pathways of
      generation of the primary ROS and the defense methods used by fungi and yeasts
      against them as well as the involvement of thiol compounds in the antioxidant
      defense of the fungal cell. It is demonstrated that the adaptation of fungi to
      oxidative stress is tightly connected with the redox-dependent changes in the
      activities of antioxidant defense components.

PMID- 18038679
TI  - [Laccase-mediator systems and their applications: a review].
AB  - The mechanism of operation of laccase-mediator systems (LMSs) in xenobiotic
      degradation mediated by "true" redox mediators and laccase enhancing agents is
      considered. Structural formulae of most common laccase mediators and compounds
      that can be used as agents enhancing the enzyme operation are presented. Examples
      of LMS application in biotechnology are described.

PMID- 18038678
TI  - [Oxidation processes at initial stages of interaction of root nodule bacteria
      (Rhizobium leguminosarum) and pea (Pisum sativum L.): a review].
AB  - A possible physiological mechanism of legume-Rhizobium symbiosis, consisting in
      regulation of the intensity of oxidation processes by the microsymbiont in
      response to infection with Rhizobium, was analyzed using our own and published
      data. The results used in the analysis included data on the content of reactive
      oxygen species (O2*-, and H2O2), activity of antioxidant enzymes (superoxide
      dismutase, catalase, and peroxidase), and intensity of lipid peroxidation
      proceeding with the involvement of lipophilic phenolic compounds of the
      microsymbiont.

PMID- 18038680
TI  - [Hybrid Mn-peroxidases from basidiomycetes: a review].
AB  - The Mn-peroxidase from the fungus Panus tigrinus 8/18 is a hybrid enzyme. It
      catalyzes both Mn2+-dependent and Mn2+-independent oxidation of organic
      substrates. The spectral properties of intermediates and the pathway of the
      catalytic cycle are typical of hybrid Mn-peroxidases. The enzyme catalyzes the
      "oxidase" reaction (NADH oxidation) without peroxide and with the presence of
      Mn2+, which takes part in hydrogen peroxide production via Mn3+ and preserves the
      enzyme from inactivation. With the presence of organic mediators, the hybrid Mn
      peroxidase oxidizes nonphenolic compounds: aromatic alcohols and a nonphenolic
      lignin model compound. The degree of conversion of 2,4,6-trichlorophenol is
      higher with the presence of l-hydroxybenzotriazole.

PMID- 18038681
TI  - [Dissimilatory nitrate reduction in fungi under conditions of hypoxia and anoxia:
      a review].
AB  - Recent progress in studies of anaerobic nitrate reduction and nitrous oxide
      formation in fungi has been reviewed. Current understanding of the biochemistry
      of nitrate and nitrite reduction to nitrous oxide and ammonium under oxygen
      limitation is presented, with emphasis on patterns of fungal co-denitrification,
      properties of the enzymes involved, and prevalence of nitrate respiration among
      fungal species.

PMID- 18038682
TI  - [Use of soybean peroxidase for the enzyme immunoassay of sulfamethoxipyridazine
      in milk].
AB  - An enzyme immunoassay with colorimetric detection of sulfamethoxipyridazine
      (SMP), the most widely used sulfamide, was developed with the soybean anionic
      peroxidase as an enzyme marker. The range of SMP detection is 1.3-63.0 ng/ml with
      a detection limit of 0.4 ng/ml. The root square deviation of detection results
      did not exceed 6%. It was demonstrated that 0.15% casein added to the working
      buffer prevented the effect of the milk matrix on the detection. The results
      obtained demonstrate that the assay developed is promising, displaying a
      sensitivity that exceeds the maximum permissible concentration of sulfamides in
      milk (100 microg/l) by several orders of magnitude.

PMID- 18038683
TI  - [Antioxidant enzyme complex of tissues of the bivalve Mytilus galloprovincialis
      Lam. under normal and oxidative-stress conditions: a review].
AB  - The results of studies of tissue specifics of the enzymatic antioxidant complex
      of the bivalve Mytilus galloprovincialis Lam. are summarized. It is shown that
      the highest oxidative load is experienced by gills. The antioxidant complex of
      gills largely depends on environmental conditions than on the mollusk's state,
      which allows this tissue to be used for ecological diagnostics. A decrease in the
      content of carotenoids in tissue s suppressed the activities of the key enzymes
      of antiradical defense-superoxide dismutase (SOD) and catalase-and is accompanied
      by a decrease in the reduced glutathione (GSH) pool. The state of the antioxidant
      complex of molluscan tissues under conditions of natural (spawning) and
      artificial (exposure to a cationic surfactant) oxidative stress was studied.

PMID- 18038684
TI  - What is psychocutaneous medicine?

PMID- 18038685
TI  - Successful treatment of auricular pseudocyst using a surgical bolster.

PMID- 18038686
TI  - Re. Floating lipoma: an unusual presentation of a common tumor.

PMID- 18038687
TI  - What is your diagnosis? Neonatal lupus erythematosus.

PMID- 18038688
TI  - Aquatic antagonists: sponge dermatitis.

PMID- 18038689
TI  - Unilateral facial angiofibromas without other evidence of tuberous sclerosis:
      case report and review of the literature.
AB  - Bilateral facial angiofibromas are common cutaneous manifestations of tuberous
      sclerosis, an autosomal-dominant disease characterized by hamartomas of multiple
      organs. Papules in patients with tuberous sclerosis typically appear between 4
      and 10 years of age, becoming more extensive during puberty before stabilizing.
      We present a 28-year-old man with unilateral facial angiofibromas, which may
      represent a segmental form of tuberous sclerosis.

PMID- 18038690
TI  - Pancreatic panniculitis associated with acinic cell adenocarcinoma: a case report
      and review of the literature.
AB  - Pancreatic panniculitis represents a rare skin manifestation of underlying
      pancreatic pathology. The clinical presentation of the condition is remarkably
      consistent and privy to several unique clinical and histopathologic findings. We
      report a case of a 50-year-old white woman with pancreatic panniculitis and newly
      diagnosed pancreatic acinic cell adenocarcinoma. The clinical and histopathologic
      features, underlying causes, and treatments are reviewed.

PMID- 18038691
TI  - Proteus syndrome: 2 case reports and a review of the literature.
AB  - Proteus syndrome is a rare condition that has a variable clinical presentation.
      The syndrome is characterized by asymmetric disproportionate enlargement of the
      limbs, skull, or vertebrae, associated with a number of cutaneous lesions.
      Herein, the clinical findings of 2 patients with Proteus syndrome are presented
      and the current clinical diagnostic criteria are reviewed.

PMID- 18038692
TI  - Chronic arsenicism from Chinese herbal medicine.
AB  - Chronic arsenicism is associated with cutaneous manifestations, including
      palmoplantar keratoses, pigmentary anomalies, and nonmelanoma skin cancer. It
      occurs most commonly following exposure to inorganic arsenic in contaminated
      drinking water or occupational contact, though medicinal exposure also has been
      reported. We present a case of a Chinese woman living in the United States with
      cutaneous manifestations of chronic arsenicism due to a 5-year history of Chinese
      herbal medicine ingestion.

PMID- 18038693
TI  - Disseminated histoplasmosis in a patient with AIDS: case report and review of the
      literature.
AB  - Disseminated histoplasmosis was uncommon prior to the AIDS epidemic, and
      cutaneous eruption rarely was seen. Since the onset of the worldwide AIDS
      epidemic, histoplasmosis has become a more common opportunistic fungal infection
      and should be considered in the differential diagnosis of mucocutaneous lesions
      in patients with AIDS in endemic areas. We report a case of classic disseminated
      histoplasmosis in a patient with AIDS and discuss the epidemiology, clinical
      presentation, pathogenesis, laboratory and histopathologic findings, and
      treatment options for disseminated histoplasmosis.

PMID- 18038694
TI  - Necrotizing sarcoid granulomatosis with skin and pulmonary involvement.
AB  - We present a rare case of necrotizing sarcoid granulomatosis (NSG) with skin and
      pulmonary involvement. NSG with extrapulmonary involvement occurs infrequently,
      and reports involving skin manifestations in NSG are even more rare.

PMID- 18038695
TI  - Laptop computer--associated erythema ab igne.
AB  - A 40-year-old woman presented with an asymptomatic reticulated eruption on the
      thighs. After an extensive workup, she was diagnosed with erythema ab igne caused
      by laptop computer use. The eruption ultimately cleared several months after
      discontinuation of direct placement of the laptop computer on her thighs.
      Erythema ab igne is becoming increasingly associated with exposure to modern heat
      sources. A thorough history of patients with suspicious lesions should include
      questioning for contact with alternative heat sources to avoid an unnecessary
      workup for this condition.

PMID- 18038696
TI  - Lipedematous alopecia: spongy scalp syndrome.
AB  - Lipedematous scalp and lipedematous alopecia are rare and closely related
      entities of unknown etiology Almost all cases have occurred in black women. We
      report a case of lipedematous alopecia that is characterized by a boggy spongy
      thickening of the scalp, an increase in subcutaneous fat, short hairs, patchy
      alopecia, scarring, atrophy, and depigmentation. The histologic finding of an
      increase in subcutaneous adipose tissue is notable.

PMID- 18038697
TI  - Gender differences in dermatologists' annual incomes.
AB  - Careful examination of the relationship between dermatologists' gender and their
      incomes has not been conducted. We sought to determine the association between
      gender and the net annual incomes of dermatologists after controlling for
      physician work effort, provider characteristics, and practice characteristics. We
      conducted a retrospective analysis of survey data collected from 266 actively
      practicing office-based dermatologists who self-identified as white, lived in the
      United States, graduated from US medical schools, and responded to the annual
      American Medical Association (AMA) survey of physicians between 1992 and 2002.
      White female dermatologists reported seeing 21% fewer patients and working 16%
      fewer annual hours than white male dermatologists. White female dermatologists
      had practiced medicine for fewer years than white male dermatologists, were more
      likely to be employees as opposed to having an ownership interest in the
      practice, and were equally likely to be board certified. After adjustment for
      work effort, provider characteristics, and practice characteristics, the mean
      annual income of white female dermatologists was $215,311, or $81,746 (28%) lower
      than white male dermatologists (95% CI, $138,098 lower to $25,393 lower; P=.005).
      Our findings were limited to white dermatologists and to analysis of data
      collected in the surveys; we were not able to examine alternative explanations
      for the income disparities that we found. During the 1990s, female gender was
      associated with lower annual incomes among dermatologists practicing in the
      United States. Researchers should further explore the relationship between the
      gender and incomes of physicians to determine what additional factors might cause
      the differences that we found.

PMID- 18038699
TI  - Short-term corticosteroids and avascular necrosis: medical and legal realities.
AB  - Short-term corticosteroids (CSs), most commonly defined as short-term prednisone
      (STP) 40 to 60 mg or its equivalent, either tapered or level, prescribed over a
      few days to 3 weeks (total dose, 400-600 mg), often are used to treat acute and
      self-limiting diseases. Serious side effects, though uncommon, can occur;
      however, they receive little attention. The literature contains scattered case
      reports and legal cases that highlight the relationship between STP and avascular
      necrosis (AVN). The orthopedic literature finds that CSs are one of the most
      common causes of AVN. An Internet search of AVN identifies several commercial
      pages prepared for lawyers that describe references and supplies relevant to
      initiating lawsuits. Court cases consistently find that patients must be informed
      of treatment risks and options. Informed consent and thorough documentation are
      required when prescribing STP.

PMID- 18038698
TI  - Rituximab therapy in severe juvenile pemphigus vulgaris.
AB  - Juvenile pemphigus vulgaris (PV) is a rare and often misdiagnosed condition.
      Although PV frequently is severe in children, a substantial portion of the
      morbidity and mortality associated with juvenile PV has been attributed to
      treatment. This report demonstrates the efficacy of rituximab therapy in juvenile
      PV. We report 2 cases and review the literature. Rituximab treatment was
      effective in helping to control 2 recalcitrant cases of juvenile PV without
      inducing the adverse effects associated with other adjuvant therapies. Rituximab
      should be considered when treating resistant cases of PV in pediatric populations
      to avoid the long-term side effects of other immunosuppressive treatments.

PMID- 18038700
TI  - Microcystic adnexal carcinoma arising within a nevus sebaceus.
AB  - Nevus sebaceus (NS) is a congenital skin lesion arising on the face and scalp
      that has been linked to the development of various carcinomas. We describe a case
      of microcystic adnexal carcinoma (MAC) arising in an NS on the scalp of a 62-year
      old man. Excisional skin biopsy and hematoxylin and eosin stains were performed
      to examine the specimen. Serial sections revealed papillomatosis typical of NS,
      with focal changes consistent with syringocystadenoma papilliferum. Adjacent to
      the syringocystadenoma papilliferum was an area containing small epithelial
      islands that extended focally into the subcutaneous layer. The cystic islands
      were embedded in a desmoplastic stroma with poor circumscription, consistent with
      MAC. This case presents a rare finding of MAC within an NS.

PMID- 18038701
TI  - The role of ketoconazole in seborrheic dermatitis.
AB  - Although the prominent broad-spectrum activity of ketoconazole was reported in
      the early 1980s, its effect against Malassezia species was most pronounced; thus,
      it was developed for the treatment of various skin infections in which a link
      with these fungal species was proposed. Later, a number of ancillary properties
      were described for ketoconazole that comprised its anti-inflammatory,
      antiseborrheic, and antiproliferative profile. The incorporation of ketoconazole
      in an adapted vehicle could further promote its efficacy. Recently, a new
      formulation-an anhydrous gel containing ketoconazole 2%-was launched in which all
      of the ancillary properties were optimized.

PMID- 18038702
TI  - Graves' disease therapy in children: truth and inevitable consequences.

PMID- 18038703
TI  - Autoimmune type 2 diabetes mellitus and rational classification.

PMID- 18038704
TI  - Juvenile autoimmune thyroiditis.
AB  - Autoimmune thyroiditis is a frequent cause of goiter in children and studies
      point to the increasing prevalence of juvenile autoimmune thyroiditis (JAT) in
      children and adolescents. Clinically, JAT can manifest, depending on the presence
      or absence of goiter, as either a goitrous form or atrophic form. Both are
      characterized by the presence of thyroid antibodies in serum, with the goitrous
      form being more common in children. Recent evidence suggests that thyroid
      autoimmunity originates from an interaction of genetic, endogenous and
      environmental factors which end up activating thyroid-specific autoreactive T
      cells in susceptible children. In addition to underlying genetic/HLA
      predisposition, factors including sex hormones, glucocorticoids, low birth
      weight, radiation and drugs may play a role in thyroid autoimmunity. Patients
      with JAT can present due to thyroid enlargement or symptoms arising due to
      hypothyroidism. Asymptomatic enlargement of the thyroid gland is a common
      presenting complaint, especially in older children and adolescents. Thyroid
      function can vary from euthyroidism to subclinical or overt forms of
      hypothyroidism and less commonly hyperthyroidism. Accordingly, patients can be
      symptomatic. There is considerable debate regarding the management of patients
      with euthyroidism or subclinical hypothyroidism. Available evidence indicates the
      presence of residual goiter in endemic form and a high prevalence of JAT in
      children. It is suggested that children should be screened for goiter as part of
      school health examinations, and goitrous children should be monitored for thyroid
      function.

PMID- 18038705
TI  - Natal teeth and neonatal transient pseudohypoparathyroidism in a newborn.

PMID- 18038706
TI  - Clinical course of pediatric and adolescent Graves' disease treated with
      radioactive iodine.
AB  - The use of radioactive iodine (RAI) therapy in children and adolescents with
      Graves' disease is increasing; however, few data exist to guide dosing in this
      population. We aimed to determine the clinical course, failure rate and factors
      associated with failure of RAI for pediatric Graves' disease. A retrospective
      chart review from a tertiary care pediatric endocrinology clinic (1990-2003)
      identified 22 patients (12.7 +/- 4.0 years at diagnosis) with Graves' disease
      treated with RAI after initial pharmacological therapy. Patients received a
      calculated dose of RAI (0.1 mCi/g thyroid tissue, adjusted for 6-h radio-iodine
      uptake). Twenty-seven percent (95% CI 11-50%) remained hyperthyroid and required
      a second dose. If the first RAI was successful, the average time to
      hypothyroidism was 2.96 +/- 1.05 months. There were no statistically significant
      differences between those successfully treated with one dose and those requiring
      re-treatment. This high failure rate indicates a need to examine dosing of RAI in
      this age group.

PMID- 18038707
TI  - Prevalence and clinical features of type 1.5 diabetes mellitus in children.
AB  - AIM: To classify children with diabetes mellitus as type 1, 1.5 or 2, based on
      strict criteria, and then compare their features and treatment. METHODS: In this
      retrospective study, all children with diabetes mellitus in our clinic with
      antibody status available (n = 120) were reclassified as type 1, 1.5 or type 2
      based on status of antibodies to the pancreas and presence of obesity and/or
      acanthosis nigricans, and their features compared. RESULTS: Sixty-four percent of
      type 2 patients were reclassified as type 1.5. Type 1.5 patients had
      significantly lower BMI SDS, blood pressure and acanthosis nigricans than type 2
      patients. They had a higher insulin requirement (0.82 +/- 0.44 U/kg/day) than
      type 1 (0.72 +/- 0.35 U/kg/day) or type 2 (0.28 +/- 0.3 U/kg/day) patients. Total
      cholesterol, HDL-cholesterol, ALT and AST significantly worsened from type 1 to
      1.5 to type 2 patients. CONCLUSIONS: Type 1.5 diabetes mellitus should be
      considered among obese adolescents presenting as type 2, as their clinical course
      is more aggressive and insulin requirement higher.

PMID- 18038708
TI  - Characterization of insulin resistance syndrome in children and young adults.
      When to screen for prediabetes?
AB  - CONTEXT: Insulin resistance syndrome (IRS) is associated with the development of
      type 2 diabetes mellitus (DM2). However, it is unclear which individuals with
      insulin resistance will develop DM2. AIM: To study the prevalence of IRS in
      childhood and to identify the group with the highest risk of further progression
      to DM2. METHODS: In a cross-sectional study, 86 obese individuals underwent an
      intravenous glucose tolerance test (IVGTT). Insulin resistance index (Si(IVGTT)),
      acute insulin response (AIR) and disposition index (DI) were calculated from
      IVGTT. RESULTS: For analysis the participants were divided into insulin-sensitive
      (IS) (n = 25, 13.3 +/- 5.9 yr) and insulin-resistant (IR) groups on the basis of
      having an Si(IVGTT) greater or lesser than 4.5 x 10(-4) mU/ml/min, respectively.
      The IR group was then subdivided according to DI, with the standard cut-off value
      of 0.13 min(-1), into compensated IR (CIR) (n = 37, 13.0 +/- 3.5 yr) and
      decompensated IR (DIR) (n = 24, 21.9 +/- 12.6 yr) groups. The frequency of IRS
      was 43% in children, 78% in adolescents and 83.6% in adults. Decompensated
      insulin response first appeared during adolescence. The frequency of
      decompensation increased from 22% in adolescence to 67% in adulthood. The DIR
      group had increased triglycerides (TG) and urinary free cortisol levels.
      CONCLUSIONS: The frequency and severity of IR increases with age. Decompensation
      first presents in adolescence with low AIR and elevated TG. Decompensated
      adolescents are the group at highest risk for further progression to DM2.

PMID- 18038709
TI  - Factors contributing to sex assignment and reassignment decisions in Turkish
      children with 46,XY disorders of sex development.
AB  - BACKGROUND: Sex assignment decisions for children with disorders of sex
      development (DSD) should be based on integrative assessments of relevant
      biological and psychosocial characteristics. AIM: To investigate the factors that
      contributed to sex assignment decisions for children with 46,XY DSD. PATIENTS:
      Sixty-one children recruited from a clinical sample were evaluated. METHODS:
      Findings of endocrinological and psychiatric evaluations were entered into a
      logistic regression analysis. RESULTS: Gender identity was the strongest
      correlate of assigned sex. External genital under-virilization, sex announced at
      birth and toy/ activity preferences were predominant predictors. Twelve children,
      six of whom were prepubertal, were reassigned to male sex. CONCLUSIONS:
      Psychological factors seem to be as influential on sex reassignment decisions as
      are endocrinological and social factors, especially if the disorder is diagnosed
      at an older age. Prepubertal gender conversion is possible, which implies the
      importance of follow-up during childhood.

PMID- 18038710
TI  - Growth and development are similar in VLBW children born appropriate and small
      for gestational age: an interim report on 97 preschool children.
AB  - AIM: To investigate growth and development in a cohort of children born with very
      low birth weight (VLBW) treated at a single tertiary neonatal unit. METHODS: We
      studied 97 children born between January 1995 and July 1997 with BW <1,500 g. At
      follow-up (mean age 3.7 years) anthropometric data and data on neurological
      status, motor, speech and language development were collected. Small for
      gestational age (SGA) was defined as weight and/or length at birth <10th
      percentile; shortness at follow-up was defined as height <10th percentile.
      RESULTS: Comparison was made between the appropriate for gestational age (AGA) (n
      = 46) and SGA (n = 51) groups. At follow-up, 23 AGA and 35 SGA children were
      short, had a smaller head circumference (-1.9 vs -0.8 SDS), were lighter at birth
      (BW -1.3 vs -0.7 SDS), and had a higher rate of broncho-pulmonary dysplasia (BPD)
      (28 vs 12); no differences in neonatal characteristics or neurological status
      were evident. A higher frequency of motor delay occurred in the 'short' group.
      Short children also had a smaller head circumference (HC) (-1.6 vs -0.7). Short
      SGA children had a higher frequency of BPD, smaller HC (-2.1 vs -1.0), and a
      slightly higher proportion of suspicious neurological findings, motor delay, and
      speech and language delay (n.s.). CONCLUSIONS: Preterm VLBW infants, whether AGA
      or SGA at birth, face the risk of being short at preschool age. Height outcome is
      probably influenced by postnatal factors. Our data also suggest that short
      stature is associated with developmental difficulties in this population.

PMID- 18038711
TI  - Serum ghrelin concentration, fasting time and feeding in infants.
AB  - BACKGROUND: Data on hormonal feeding control in infants in the first months of
      life according to the kind of feeding are scanty. AIM: To evaluate whether serum
      ghrelin could be involved in feeding behaviour control of breast-fed (BF) and
      formula fed (FF) infants. METHODS: We studied 50 AGA healthy term infants aged 1
      6 months of age. Serum ghrelin concentration was determined by RIA. Fasting time
      (measured as the difference between the time of the last meal and the time of
      blood collection) and number of meals were recorded. RESULTS: A positive
      correlation between serum ghrelin levels and fasting time emerged in FF infants
      (r = 0.752; p <0.001) but not in BF infants (r = 0.345; p = 0.072). CONCLUSIONS:
      Circulating ghrelin concentration correlates positively with fasting time in FF
      infants; these infants have higher serum ghrelin concentration, longer fasting
      time and fewer meals than BF infants. These observations suggest a possible
      influence of early feeding on mechanisms regulating satiety and feeding
      behaviour.

PMID- 18038712
TI  - Recurrent hypoglycemic seizures and obesity: delayed diagnosis of an insulinoma
      in a 15 year-old boy--final diagnostic localization with endosonography.
AB  - Insulinoma in children and adolescents is extremely rare. In adults diagnosis is
      frequently delayed due to frequent neuropsychiatric symptoms that are
      misunderstood. Diagnostic localization is sometimes extremely difficult. We
      present a case of insulinoma with onset of symptoms at the age of 12.5 years.
      Diagnosis was made very soon after the first symptoms, but diagnostic
      localization was delayed, since conventional MRI did not reveal the insulinoma.
      The patient suffered from recurrent hypoglycemic seizures and gained 54 kg in
      weight until diagnostic localization was made with abdominal MRI, octreotate-PET
      and finally successful endosonography. A solitary insulinoma in the pancreatic
      tail was enucleated laparoscopically.

PMID- 18038713
TI  - A new DAX-1 mutation in a family with a case of neonatal adrenal insufficiency
      and a sibling with adrenal hypoplasia and sudden death at 3 years of age.
AB  - Adrenal hypoplasia congenita (AHC) is a hereditary disorder that leads to adrenal
      insufficiency and hypogonadotropic hypogonadism (HHG) in childhood. The gene
      responsible for the X-linked form of AHC, DAX1 (dosage-sensitive sex-reversal,
      AHC, on the X-chromosome, gene 1)/NR0B1, encodes for a nuclear factor which lacks
      the characteristic zinc finger DNA-binding domain that is highly conserved in
      nuclear receptors. Deletions and point mutations in the DAX1 gene have been
      described in more than 70 AHC families. We present the clinical and genetic data
      of two brothers affected by AHC. We report a new DAX1 gene mutation in a family
      with two affected members: one with neonatal adrenal insufficiency, and a sibling
      with adrenal hypoplasia and sudden death at 3 years old. The NR0B1/DAX1 gene was
      amplified in three PCR fragments from the patient's and mother's gDNA extracted
      from peripheral lymphocytes. Sequencing revealed a novel single nucleotide
      deletion in codon 419 from exon 2 that resulted in a frameshift and a stop codon
      17 nucleotides downstream (c.1256 delA). The mother was heterozygous for this
      mutation. In conclusion, a novel DAX-1 mutation was detected in two family
      members with different phenotype: one live infant with adrenal hypoplasia, his
      mother, and probably his dead brother.

PMID- 18038714
TI  - Effect of metformin and rosiglitazone in a prepubertal boy with Alstrom syndrome.
AB  - Alstrom syndrome (AS) is an autosomal recessive disorder characterized by
      progressive pigmentary retinopathy, sensorineural hearing loss, fatty liver
      infiltration, obesity, insulin resistance and early-onset type 2 diabetes
      mellitus (DM2). Early onset of insulin resistance and DM2 are key components of
      this syndrome. AIM: To study the effect of early initiation of the insulin
      sensitizer metformin combined with rosiglitazone in a patient with AS with
      impaired glucose tolerance. PATIENT: An 8 year-old boy with AS presented with
      acanthosis nigricans and insulin resistance at the age of 6 years. He had
      progressive excessive weight gain from 9 months of age. By the age of 1 year he
      developed photosensitivity, blindness and nystagmus. At the age of 5.5 years, his
      body mass index (BMI) was above the 95th percentile. He developed impaired
      glucose tolerance at 6 years of age and treatment with metformin was initiated.
      After 8 months of treatment with metformin he developed DM2. The dose of
      metformin was increased, and rosiglitazone added. METHODS: A 2-hour oral glucose
      tolerance test (OGTT) and a rapid intravenous glucose tolerance test (IVGTT) were
      performed before treatment was initiated, after treatment with metformin and at
      the end of 1 year of combination therapy with metformin and rosiglitazone to
      calculate quantitative insulin sensitivity check index (QUICKI) and acute insulin
      response (AIR). For mutation analysis, all exons and splice site sequences of the
      ALMS1 gene were amplified and sequenced. RESULTS: Metformin treatment alone at
      the stage of impaired glucose tolerance did not prevent progression to DM2.
      However, metformin at a higher dose and in combination with rosiglitazone
      resulted in improvement of pancreatic beta-cell function, shown by markedly
      improved first-phase insulin response to glucose measured by AIR. The patient was
      found to have two heterozygous nonsense mutations in ALMS1, 8008 C-->T Ter,
      R2670X, and 11449 C-->T Ter, Q3817X. These alterations cause premature stops and
      result in a truncated ALMS1 protein. CONCLUSION: We suggest that early initiation
      of combined therapy comprising a high dose of metformin plus rosiglitazone may be
      valuable in managing insulin resistance and DM2 in children with AS.

PMID- 18038715
TI  - Predictable cementation of esthetic restorations: part I--principles of adhesion.
AB  - Cementation is a multifaceted procedure in restorative and esthetic dentistry,
      principally involving the adaptation of cement to the tooth surface in a manner
      that prevents the detachment of a restoration during patient function. In each
      procedure, the goal of the practitioner is to create a lasting bond and marginal
      adaptation of the luting cement between the indirect restoration and the
      remaining tooth structure. This article highlights the relevant principles of
      adhesion and presents criteria aimed at improving clinicians' decision making
      while providing daily patient care.

PMID- 18038716
TI  - Predictable cementation of esthetic restorations: part II--selection criteria and
      guidelines for implementation.
AB  - Patient demand for esthetic dentistry has increased clinicians' use of composite
      resin luting agents for cementing both intra- and extracoronal restorations. The
      cementation process is key to the success of such treatment to prevent
      microleakage, ensure sufficient retention of the restoration to the tooth
      substrate, and provide the physical strength required of the restoration. Recent
      advances in adhesive technology have expanded the options available to the
      practitioner when selecting a restorative material and luting cement, and new
      guidelines must be understood accordingly.

PMID- 18038717
TI  - Predictable elastomeric impressions in advanced fixed prosthodontics: a
      comprehensive review.
AB  - Despite advances in dental material technology, the predictable procurement of
      accurate impressions for the fabrication of complex fixed prosthodontic
      restorations remains an elusive objective. The technical challenges and potential
      negative sequelae are exponentially magnified in advanced applications that
      involve multiple abutments and preparatory phases. A protocol for consistently
      achieving accurate impressions with the use of various impression materials and
      automatic instrumentation is presented and illustrated with multiple clinical
      examples. The technique is capable of yielding reliable results in extensive
      cases and requires minimal support from auxiliary personnel.

PMID- 18038718
TI  - Understanding anesthesia guidelines for improved patient awareness.

PMID- 18038719
TI  - Anterior restoration utilizing novel all-ceramic materials.

PMID- 18038720
TI  - The evolving e-practice. Predictable visualization and imaging using three
      dimensional cone beam technologies.

PMID- 18038721
TI  - Changing the perception of root canal therapy.

PMID- 18038722
TI  - Direct inlay restorations: utilization of sonic preparation technology in
      conjunction with ceramic inserts.
AB  - Although glass inserts have enabled the use of direct restorative procedures for
      the placement of inlays and onlays, these techniques are often unable to address
      elementary patient concerns (i.e., aesthetics, fit, expense). The advent of a
      novel process that standardizes preparation design and facilitates the use of
      advanced restorative materials may provide an alternate means of providing
      acceptable treatment. This article highlights the use of a sonic preparation
      system with ceramic inserts to develop aesthetic direct inlay restorations that
      demonstrate the qualities traditionally exhibited by indirect ceramic materials.

PMID- 18038723
TI  - Methods to improve the clinical effectiveness of current dentin-enamel bonding
      agents.

PMID- 18038725
TI  - Why does President Bush oppose the expansion of SCHIP?

PMID- 18038724
TI  - Bone rehabilitation to achieve optimal aesthetics.
AB  - Treatment involving oral implants has established a high success rate, including
      implant survival on a long-term basis. The challenge facing the clinicians today
      is to achieve an optimal long-term aesthetic result. To address this challenge,
      the volume of the underlying hard and soft tissue must be restored either prior
      to or simultaneously with the implant placement. The learning objective of this
      article is to review the critical biologic and clinical criteria essential in
      achieving a predictable success in aesthetic enhancement of the implant site.

PMID- 18038726
TI  - Coping with stressful events: influence of parental alcoholism and race in a
      community sample of women.
AB  - The study explores the role of race and differences in coping among 290 white
      women and black women with and without alcoholic parents, addressing two
      questions: (1) Does coping vary by parental alcoholism or race? and (2) How is
      coping in adulthood affected by childhood stressors and resources and by
      adulthood resources? Standardized self-administered questionnaires (Coping
      Responses Inventory and the Children of Alcoholics Screening Test) measuring
      approach and avoidant coping methods were used. Collateral information was
      obtained from siblings who completed questionnaires focused on parental drinking,
      parental psychiatric history, and key childhood events. Women with alcoholic
      parents and black women more often reported avoidant coping. Women with negative
      childhood family environments and a lack of adolescent social support more often
      reported avoidant coping responses. Self-esteem was associated with a higher
      score on active cognitive coping and a lower score on avoidant coping. Findings
      of greater use of avoidant coping by women with alcoholic parents contrast with
      other studies showing no differences in coping, or very small group differences.
      The fact that all women in this sample lived with two parents in childhood may be
      one explanation.

PMID- 18038727
TI  - HIV/AIDS case managers and client HIV status disclosure: perceived client needs,
      practices, and services.
AB  - People living with HIV/AIDS often need assistance in deciding whether or how to
      disclose their HIV status to others, and case managers are in a unique position
      to offer this assistance. The current study surveyed 223 case managers providing
      services to people living with HIV/ AIDS in NewYork State. The survey was
      conducted anonymously, and case managers were sampled at the agency level.
      Results showed that two-thirds of case managers routinely discuss disclosure
      issues with their HIV-positive clients. However, case managers often felt that
      they lacked the resources to provide assistance with disclosure decisions, and 66
      percent of those who routinely discuss disclosure issues had not received
      training in assisting with disclosure to sex and injection drug-sharing partners.
      HIV disclosure issues were also seen by case managers as only one of many
      pressing issues facing their HIV-positive clients; other pressing issues were
      housing, food, medical care, mental health treatment, and preventing HIV
      transmission. These results indicate a need for training and resources to
      facilitate HIV status disclosure assistance services offered by case managers.

PMID- 18038728
TI  - An integrated, multidimensional treatment model for individuals living with HIV,
      mental illness, and substance abuse.
AB  - The challenge of providing effective treatment services for the growing
      population of HIV-positive individuals who are also dually diagnosed with
      substance use and mental disorders has only recently been recognized as an
      important public health concern affecting both HIV treatment and prevention. This
      article describes a treatment model that was created for a study of integrated
      treatment for HIV-positive individuals with substance use and mental disorders.
      The treatment model was based on the transtheoretical model of behavior change as
      well as evidence-based practices that are widely used in the treatment of
      individuals dually diagnosed with substance use and mental disorders. The model
      involved collaboration between medical and behavioral health care professionals
      and emphasized the importance of goal reinforcement across disciplines.
      Furthermore, it included the development and enhancement of client motivation to
      modify medical and behavioral health-risk behaviors using individual readiness
      for change and offered comprehensive care addressing a continuum of client needs
      that may influence treatment outcomes. Treatment modalities included individual
      therapy, group therapy, and psychiatric medication management. This treatment
      intervention was associated with positive outcomes in the integrated treatment
      study and can be adapted for use in a variety of psychiatric or medical treatment
      settings.

PMID- 18038729
TI  - Diabetes and adult day health services.
AB  - The purpose of this study is to provide a profile of individuals with diabetes
      who receive services in adult day centers. This exploratory study uses an
      administrative data set (N = 280) from five programs in central Ohio to examine
      four areas: demographics, health and mental health, financial and social
      resources, and disenrollment status. Older adults with diabetes were more likely
      to be African American and younger than other clients; had more diagnoses,
      limitations with activities of daily living, and hospitalizations; and were at
      greater nutritional risk at intake. These older adults also relied more on public
      funding, primary caregivers from the immediate family, and transportation
      assistance, and they paid less for participation in the day program. The two
      groups did not differ in length of program stay or reasons for disenrollment.
      Adult day centers serve a number of individuals with diabetes with unique needs
      and risks, providing an important location to test innovative and culturally
      responsive approaches to disease management. Caregivers are important partners in
      adult day services utilization and in diabetes management. Targeting public
      funding for diabetes care within adult day centers is recommended.

PMID- 18038730
TI  - Not just a middle-class affliction: crafting a social work research agenda on
      postpartum depression.
AB  - Postpartum depression (PPD) is a major mental health disorder that affects at
      least 13 percent of new mothers and has detrimental consequences for populations
      that are of concern to social workers, such as low-income women, women of color,
      young women, and single mothers. Despite the relevance of PPD to multiple social
      work problems and populations, the social work literature contains sparse
      information about the causes of, consequences of, and treatments for PPD among
      vulnerable groups of new mothers. In this article, the authors review the
      literature on PPD with specific attention to the sociocultural dimensions of the
      disorder, barriers to treatment, and the relationship of PPD to social work
      theory and practice. The authors argue that social workers should set an agenda
      for PPD research that draws on the profession's biopsychosocial perspective,
      advances a culturally competent understanding of the experience of PPD, and
      informs social work practice with diverse groups of new mothers.

PMID- 18038731
TI  - Bringing it all back home: social work and the challenge of returning veterans.

PMID- 18038732
TI  - Social justice, respect, and meaning-making: keys to working with the homeless
      elderly population.

PMID- 18038733
TI  - The making of a resource center for homeless people in San Francisco's Mission
      District: a community collaboration.

PMID- 18038734
TI  - The new 80.

PMID- 18038735
TI  - Starving with age.

PMID- 18038736
TI  - Fatal missteps.

PMID- 18038737
TI  - Geriatric gamers.

PMID- 18038738
TI  - Physician autonomy in the age of accountability.

PMID- 18038739
TI  - The memory keepers.

PMID- 18038740
TI  - Coming of age.

PMID- 18038741
TI  - Candles, dishwashers and Alzheimer's disease.

PMID- 18038742
TI  - Genes, aging, and prospects for extended life span.
AB  - Our current understanding of the genetics of aging stems largely from 2 decades
      of research involving animal models. The research is yielding evidence that aging
      is a complicated process involving multiple genes and their interactions. It is
      also showing that aging and life span can be manipulated. This article highlights
      findings from these studies and discusses their implications. It also highlights
      other research on humans and aging. The author makes the point that genetic
      research will likely lead to longer human life spans but that change will be
      incremental.

PMID- 18038743
TI  - Sleep complaints in the geriatric patient.
AB  - Difficulty sleeping is a frequent complaint of elderly patients. But poor sleep
      is not a normal part of aging. This article discusses the most common sleep
      problem among older adults-insomnia, its causes, and potential treatments
      including over-the-counter and prescription medications and behavioral treatments
      such as relaxation therapy, sleep hygiene, stimulus control, sleep restriction,
      and cognitive and behavioral therapies.

PMID- 18038744
TI  - Age-related hearing loss.
AB  - Age-related hearing loss or presbycusis is hearing loss that progressively
      worsens with age. With the expected increase in the number of elderly in the
      United States, the problem is anticipated to be increasingly common, and the
      impact widely felt in coming years. This article discusses the causes and
      mechanisms of this type of hearing loss and current research that may lead to new
      treatments.

PMID- 18038745
TI  - Making child health care a political football.

PMID- 18038746
TI  - A tale of tears: finding the human touch in CKD care.

PMID- 18038748
TI  - Western habits in Mexico spur increase in diabetes.

PMID- 18038747
TI  - It's about time.

PMID- 18038749
TI  - 2005 CPMs regarding vascular access create opportunites for improving care.

PMID- 18038750
TI  - Surveillance techniques: mathematical model shows frequent testing needed during
      graft surveillance.

PMID- 18038751
TI  - Autosomal recessive PKD in the early years.

PMID- 18038752
TI  - Experience and evidence: is there enough to support funding daily in-center
      dialysis?
AB  - The dialysis community has increasingly shown the health benefits of short daily
      hemodialysis (sDHD) at home. While this appears mainly suitable for younger and
      more independent patients, it seems likely that older and frailer patients would
      benefit from short daily dialysis as well. Humber River Regional Hospital has an
      in-center daily dialysis program in Canada, offering services to 31 patients. The
      experiences of patients, challenges for the health care team, and funding issues
      are discussed and point toward a promising future for in-center daily dialysis.
      However, a need for studies of greater quality and quantity is outlined as a
      major obstacle in gaining widespread support for in-center daily dialysis from
      the funders of dialysis care.

PMID- 18038753
TI  - Should the Medicare ESRD program fund daily and nocturnal hemodialysis?
AB  - A recently published paper concluded that funding for conventional hemodialysis
      (CHD) should be maintained and that the newer methods of short daily (sDHD) and
      nocturnal home hemodialysis (NHHD) be denied funding through Medicare until a
      randomized control trial (RCT) on the benefits of sDHD and/or NHHD are complete.
      This conclusion is irrespective of the fact that RCT methodology has never been
      required of CHD itself and irrespective that a host of observational studies (OS)
      have already confirmed comparative outcome and cost benefit from these novel
      regimens. It begs the question: How can any RCT of dialysis modality, frequency,
      duration, location, and lifestyle impact ever be fairly (or ethically) completed?
      It also invokes a classic Catch-22 funding argument--funding should not be
      accorded without a fair and ethical RCT, yet a fair and ethical RCT of widely
      disparate lifestyle-impacting dialysis modalities is effectively impossible.
      Meanwhile, the better observational outcomes and cost-efficiencies of sDHD and
      NHHD remain tantalizingly attainable. It is time to recognize that a RCT may not
      be the best way to evaluate complex dialysis modalities and that available data
      is adequate to developing funding models.

PMID- 18038754
TI  - Reuse vs. single use: is the tide shifting?

PMID- 18038755
TI  - How to protect accounts receivables from medical partner and employee lawsuits.

PMID- 18038756
TI  - Key changes to the Stark II final rule. Part 1.

PMID- 18038757
TI  - Factors affecting postural stability of healthy young adults.
AB  - The objective of this paper was to examine the relationship between body
      balancing functions and body characteristics, motor abilities and reaction time.
      Subjects were 33 university students and 11 professional basketball players
      sorted into four groups of athletic and non-athletic women and men. Each group
      consisted of eleven subjects. The body height, weight was measured and the body
      mass index (BMI) calculated. A bioelectrical device computed the body fat (%).
      Static and dynamic motor tests, as well as static and dynamic balance tests were
      used. The reaction time (RT) to sound and light stimuli was measured. The
      regression analysis of the data revealed significant linear relationship between
      the amplitude of body sways (BS) and BMI in all groups. Also high correlation was
      found between back muscle strength and BS in all groups except the non-athletic
      women. Negative correlation was found between endurance capacity and BS in
      basketball players, i.e. at higher endurance capacity smaller amplitude BS
      occurred (r = -0.620, p < 0.04). The RT values showed significant correlations
      with BS only in the basketball players (r = 0.620, p < 0.04). It is concluded
      that increase in BMI, back muscle strength and endurance capacity is associated
      with better postural stability. Some motor abilities (hip flexibility, vertical
      jumping) show no significant correlations with body balancing, while other motor
      performances (static hanging) and RT values correlate well with BS only in the
      well-trained elite basketball players.

PMID- 18038758
TI  - Human submandibular gland (HSG) cell line as a model for studying salivary gland
      Ca2+ signalling mechanisms.
AB  - The human submandibular gland cell line (HSG) has been used as a model for
      studying the molecular mechanisms of salivary cells. The aim of this study was to
      investigate some aspects of salivary Ca2+ signalling. We focused on the presence
      and function of specific molecular markers of salivary cells to see whether this
      cell line retained normal salivary characteristics, despite the neoplastic
      changes. We detected the M3 acetylcholine receptor and intracellular salivary
      amylase mRNA with RT-PCR. Carbachol treatment caused a rapid, transient elevation
      of [Ca2+]i, showing that the cholinergic receptors are functional in HSG cells.
      Protein kinase C activation by phorbol-esther PMA, prior to carbachol treatment,
      inhibited the normal Ca2+ signalling pathway in HSG cells. Using selective
      antagonists, we also identified the dominant muscarinic receptor subtype M3 on
      HSG cells. We also observed that functional extracellular purinergic receptors
      were present on HSG cells and coupled to intracellular Ca2+ signalling. Our
      results suggested that the coupling mechanisms of these receptors remained
      relatively intact despite the neoplastic transformation. This enables us to use
      this cell line to model the role of muscarinic and purinergic control of salivary
      gland function, cell proliferation and differentiation.

PMID- 18038759
TI  - Enzymatic activities in brains of diabetic rats treated with vanadyl sulphate and
      sodium tungstate.
AB  - The hypothesis of the present study was that diabetes mellitus might affect brain
      metabolism. Streptozotocin (STZ)-induced diabetic rats, treated with vanadyl
      sulphate (V) and sodium tungstate (T) were employed to observe the aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK)
      activities in brain homogenates. Significant increases in AST, ALT and CK
      activities were found in diabetic brain homogenates against controls, suggesting
      increments of transamination in brain and/or increases in cell membrane
      permeability to these enzymes. The increase in brain CK possibly expresses
      alterations in energy production. The decrease in CK activity caused by V and T
      treatment in diabetic rats suggests that both agents tend to normalize energy
      consumption. It is also possible that V and T-induced hypoglycemic effects cause
      metabolic alterations in brain.

PMID- 18038760
TI  - Methyl jasmonate induced apoptosis in human prostate carcinoma cells via 5
      lipoxygenase dependent pathway.
AB  - Methyl jasmonate--a plant stress hormone with striking resemblance to
      lipoxygenase products have been reported to induce apoptosis in several cancers.
      However, 5-HETE--a product of the lipoxygenase pathway has been implicated in
      human prostate cancer progression and yet possible interaction between methyl
      jasmonate and the lipoxygenase pathway has not been reported, thus, leaving some
      unanswered questions on the mechanism(s) of action by methyl jasmonate. Using
      cytotoxicity and flow cytometry assays (BrdU assay) as well as fluorescence
      microscopy, we investigated the effects of the methyl jasmonate on the
      proliferation of human prostate adenocarcinoma cell lines (DU-145, PC-3) in vitro
      and the potential interaction between methyl jasmonate and the lipoxygenase
      pathway. Methyl jasmonate (MJ) significantly (p = 0.01) inhibited the
      proliferation of human prostate carcinoma cells in dose- and kinetic-dependent
      manners and showed specific interaction with 5-lipoxygenase (5-LOX) enzyme
      pathway. Flow cytometric analyses and fluorescence microscopy confirmed that the
      inhibition of proliferation was via the induction of apoptosis. Based on our
      findings, it can be proposed that the interaction of methyl jasmonate with 5
      lipoxygenase pathway may participate in the observed anticarcinogenic property.

PMID- 18038761
TI  - Active component of a GnRH based vaccine binds to natural GnRH receptors in
      Dunning R3327-G cell line and human prostate carcinoma vesicles.
AB  - An alternative approach to immunization with native GnRH for the inhibition of
      gonadotropin secretion and gonadal function is the use of peptidomimetics such as
      peptides of GnRH that could serve as vaccines when these are joined to more
      immunogenic molecules. The GnRH sequence of many species is well-known. Reported
      consensual aminoacid sequence of mammals is: Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro
      Gly. Most of the known GnRH sequences, including birds, fish and reptiles, have
      the Glycin amino acid residue at position 6. Glycin is the smallest amino acid,
      and confers flexibility to the polypeptide chain. Glycin substitution by Prolin,
      to confer rigidity, and the coupling to a Tetanic Toxoid T helper epitope (GnRHm1
      TT), increases considerably the immune response towards the autolog GnRH when it
      is administered using an oily adjuvant. In the present study we also investigate
      the capacity of GnRHm1-TT (active component of a GnRH based vaccine) to bind the
      natural GnRH receptor in Dunning R3327-G cell line and vesicles of different
      tissues when administered without an adjuvant. Results showed that GnRHm1-TT do
      not lose the binding ability to natural GnRH receptor in vitro and in vivo. We
      also demonstrated that this molecule behaves as a GnRH agonist analog when
      administered intraperitoneally to Wistar rats.

PMID- 18038762
TI  - Amentoflavone, a biflavonoid from Biophytum sensitivum augments lymphocyte
      proliferation, natural killer cell and antibody dependent cellular cytotoxicity
      through enhanced production of IL-2 and IFN-gamma and restrains serum sialic acid
      and gamma glutamyl transpeptidase production in tumor - bearing animals.
AB  - Modulation of immune response is highly relevant in tumor cell destruction. The
      present study is focused on the effect of amentoflavone, a biflavonoid from
      Biophytum sensitivum on cell-mediated immune responses in normal and tumor
      bearing control animals. Tumor was induced in BALB/c mice by intraperitoneal
      injection of Ehrlich ascites carcinoma cells. Treatment of amentoflavone
      significantly enhanced natural killer cell activity in normal (42.8% cell lysis)
      and tumor bearing animals (48.2% cell lysis) on the fifth day, which was much
      earlier compared to tumor-bearing control animals (20.2% cell lysis on day 9).
      Antibody-dependent cellular cytotoxicity was also increased in amentoflavone 
      treated normal (41% cell lysis on day 9) and tumor bearing animals (43.8% cell
      lysis on day 9) compared to untreated tumor bearing control animals (maximum of
      15.2% cell lysis on day 13). Amentoflavone administration could significantly
      enhance the mitogen-induced splenocyte, thymocyte, and bone marrow cell
      proliferation. Treatment of amentoflavone significantly elevated the production
      of interleukin-2 and interferon-gamma in normal and Ehrlich ascites carcinoma
      bearing animals. Moreover amentoflavone treatment significantly reduced the
      elevated levels of serum sialic acid and serum gamma glutamyl transpeptidase
      activity in tumor bearing animals.

PMID- 18038764
TI  - EGFR inhibitor-mediated apoptosis in solid tumors.
AB  - The epidermal growth factor receptor (EGFR) plays an important role in the
      development and progression of solid tumors. Growing evidence suggests that EGFR
      activation also mediates resistance to chemotherapy and radiation therapy.
      Studies elucidating the biochemical basis of these observations have demonstrated
      that EGFR inhibition down-modulates mitogen-activated protein kinase (MAPK) or
      PI3-K/Akt-dependent survival pathways in many tumor types and is associated with
      a proapoptotic shift in Bcl-2 expression and/or activation. Although research to
      date has focused on well-characterized survival pathways, other pathways in the
      complex EGFR signaling network may also be involved in tumor survival. Whereas
      suppressing EGFR signaling may be insufficient to fully induce apoptosis, it may
      prime neoplastic cells for apoptosis induced by other cytotoxic stimuli.
      Preclinical and clinical data show that inhibition of EGFR, together with
      enhanced induction of apoptosis, may counter resistance to chemotherapy and
      radiation therapy, both of which have been shown to induce EGFR-dependent
      survival responses. Further study of EGFR-modulated apoptotic pathways may
      facilitate the rational development of improved combination regimens.

PMID- 18038763
TI  - The effect of Tc-99m-labeled MDM2 antisense oligonucleotide on gene expression in
      human breast cancer MCF-7 cells.
AB  - To investigate the effect of radiolabed mouse double minute 2 (MDM2) antisense
      oligonucleotide on gene expression in human breast cancer MCF-7 cells, an
      antisense oligonucleotide (ASON) targeting MDM2 mRNA was synthesized and
      radiolabeled with 99Tcm. The labeling efficiency, radiochemical purity, and the
      ability of labeled ASON to hybridize to the sense oligonucleotides (SON) were
      investigated. To study whether the antisense probe hybridizes to respective
      sequence on MDM2 mRNA strand after radiolabeling, cells were incubated with
      radiolabeling oligonucleotides antisense oligonucleotide (0, 100, 500 nm/L) or
      mismatch oligonucleotide (ASONM) (500 nm/L) for 24 h, in the presence of
      Lipofectin 2000. RT-PCR and Western blotting was carried out to measure the MDM2
      mRNA and protein levels. The antisense oligonucleotide was radiolabeled with the
      bifunctional chelator HYNIC at the labeling efficiency of 57.2 +/- 2.98% (n = 5)
      and the mismatch oligonucleotide was 56.3 +/- 3.01% (n = 5). The radiochemical
      purity was above 95% and labeled antisense oligonucleotide has the ability to
      hybridize to the sense oligonucleotide. The levels of mRNA and protein have
      significant differences in different concentration groups. The oligonucleotide
      can be successfully radiolabeled, and specially hybridized to the MDM2 mRNA and
      inhibit gene expression intensively as compared to mismatch oligonucleotide. This
      method will be very useful in the in vivo investigation of tumor targeting.

PMID- 18038765
TI  - Development of polyclonal antibodies specific to ATP-binding cassette
      transporters human ABCG4 and mouse Abcg4: site-specific expression of mouse Abcg4
      in brain.
AB  - In our recent study on seeking new mouse ATP-binding cassette (ABC) transporters
      of the G subfamily, we succeeded in cloning mouse Abcg4 from a cDNA library of
      mouse brain, and we characterized the tissue-specific expression and chromosomal
      localization of the mouse Abcg4 gene. To further characterize the physiological
      function of mouse Abcg4 protein and to compare its function with that of ABCG2,
      in the present study, we developed polyclonal antibodies against mouse Abcg4 and
      established the Abcg4-expression system. To raise antibodies, we selected three
      different epitope peptides that correspond to the amino acid residues of 46-60,
      465-479, and 600-613 in mouse Abcg4 protein. The antibody raised against the
      epitope encoding the amino acids 46-60 was found to be specific to mouse Abcg4,
      exhibiting a band with molecular weight of 63,000 on immunoblotting, whereas this
      band was dose-dependently diminished by adding the corresponding epitope peptide
      into the immunoblot medium. Use of the antibody for immunoblot detection in mouse
      normal tissues revealed that the Abcg4 protein is expressed in brain, spleen, and
      testis. Immunohistochemical studies showed that mouse Abcg4 is site-specifically
      expressed in the cerebral cortex and medulla of mouse brain. These results
      suggest that mouse Abcg4 plays a certain physiological role in the brain. It is
      of importance to note that the sequence of amino acids 46-60 is completely
      identical between mouse Abcg4 and human ABCG4. Thus, this antibody is applicable
      to the detection of human ABCG4 as well as mouse Abcg4.

PMID- 18038766
TI  - Nrf2-dependent and -independent induction of ABC transporters ABCC1, ABCC2, and
      ABCG2 in HepG2 cells under oxidative stress.
AB  - Nrf2, an NF-E2-related transcription factor, plays a critical role in
      transcriptional upregulation of many target genes, including those for
      metabolizing enzymes and transporters essential for cellular defense in response
      to oxidative and/or electrophilic stress. In the present study, we have studied
      the potential involvement of Nrf2 in induction of human ABC transporter genes
      under oxidative stress. We created a real-time PCR primer set to quantitatively
      investigate the induction of human ABC transporters by a redox-active compound
      tert-butylhydroquinone (tBHQ) in HepG2 cells. We found that mRNA levels of ABCC1,
      ABCC2, ABCC3, and ABCG2 were significantly elevated in dose- and time-dependent
      manners. Translocation of Nrf2 into the nuclei occurred concomitantly with the
      induction of ABCC1 and ABCC2 as well as both heavy and light chains of gamma
      glutamylcysteine synthetase (gamma-GCSh and gamma-GCSI) during tBHQ treatments.
      To examine the potential involvement of Nrf2 in upregulation of the ABC
      transporters, we treated cells with siRNA to knockdown the expression of Nrf2.
      Under such Nrf2-knockdown conditions, tBHQ-induced mRNA levels of ABCC2 and ABCG2
      were significantly suppressed as were mRNA levels of gamma-GCSh and gamma-GCSI.
      Interestingly, however, the elevated mRNA level of ABCC1 was little affected by
      Nrf2 siRNA treatment. We also addressed the involvement of Keap1, which is a
      negative regulator of Nrf2 by retrieving it in the cytoplasm. When HepG2 cells
      were treated with Keap1-specifc siRNA, a significant increase was observed in
      mRNA levels of ABCC1, ABCC2, and ABCG2 as well as gamma-GCSI, suggesting that
      induction of ABCC2 and ABCG2 by tBHQ is mediated by the Nrf2/Keap1 system,
      whereas the induction of ABCC1 may involve a Keap1-dependent but Nrf2-independent
      mechanism.

PMID- 18038767
TI  - [A case of antimony resistant kala-azar cured with amphotericin B].

PMID- 18038768
TI  - [Inheritance and development of "traditional" parasitology].

PMID- 18038769
TI  - [Cloning, expression and analysis of the heat shock protein of Cryptosporidium
      andersoni].
AB  - OBJECTIVE: To clone and express the partial encoding sequence of Mr 70,000 heat
      shock protein of Cryptosporidium andersoni (CaHSP70) in Escherichia coli and
      identify the recombinant protein. METHODS: Total RNA was extracted from oocysts
      of C. andersoni isolated from Xuzhou, Jiangsu (XZ-BOV). The CaHSP70 gene was
      amplified by RT-PCR. The PCR product was cloned and then subcloned into pET28a
      vector, and the recombinant plasmids were transformed into E.coli BL21(DE3)
      subsequently. The expressed protein induced by IPTG was purified and identified
      by SDS-PAGE and Western blotting, and was further analyzed by relevant
      bioinformatics softwares. The specific IgG antibodies in mice immunized by
      rCaHSP70 were detected by Western blotting and ELISA respectively. RESULTS: The
      deduced amino acid sequence showed to be identical with that of C. andersoni Mr
      70,000 heat shock protein (HSP70). The recombinant protein expressed in the form
      of inclusion body was about Mr 43,000. It could be recognized by anti-His G
      labeled HRP antibodies and all the sera from mice infected with C. andersoni and
      children infected with C. parvum as well as sera from mice immunized with
      rCaHSP70 respectively. The rCaHSP70 possibly had multiple domains and potential
      antigenic determinants. Phylogenetic analysis showed that XZ-BOV and C. andersoni
      were in the same clade. ELISA showed that the level of specific antibodies
      against rCaHSP70 in immunized BALB/c and C57BL/6 mice was significantly higher
      than that of mice before immunization. CONCLUSION: The recombinant plasmid pET28a
      CaHSP70 has been constructed. The purified rCaHSP70 exhibits high antigenicity
      and seems a potential candidate antigen for immunodiagnosis of cryptosporidiosis.

PMID- 18038770
TI  - [Anti-Trichinella antibody level in muscle juice of experimentally infected
      mice].
AB  - OBJECTIVE: To detect the anti-Trichinella antibody level in muscle juice of
      experimentally infected mice and their correlation with serum antibodies.
      METHODS: Two hundred and eighty-eight Kunming mice were randomly divided into 3
      groups (96 mice each), each mouse was inoculated with 100, 300 or 500 muscle
      larvae of T spiralis, respectively. Anti-Trichinella antibodies in serum and
      muscle juice taken weekly up to 18 weeks post-infection (wpi) were detected by
      ELISA using T. spiralis muscle larval excretory-secretory (ES) antigens. Thirty
      mice were inoculated with T. spiralis muscle larvae(500 larvae each). The muscle
      samples taken in 6 wpi were kept in plastic containers and conserved at 4 degrees
      C for 7 days or at -20 degrees C for 20 weeks for detecting anti-Trichinella
      antibodies later. RESULTS: Anti-Trichinella antibodies in muscle juice of the
      mice infected with 100, 300 or 500 larvae were detected in 4, 3 and 3 wpi, with
      antibody positive rate of 87.5%, 50% and 87.5% respectively. In the three groups
      of mice, the antibody positive rate of muscle juice increased gradually after
      infection and up to 100% in 6, 4 and 4 wpi, and the antibody level reached its
      peak in 8 wpi with an absorbance value of 0.43, 0.49 and 0.52 respectively.
      Thereafter, the antibody level decreased slightly, but the positive rate was
      still 100% and lasted to 18 wpi when the experiment was ended. The antibody level
      in muscle juice showed significant positive correlation with serum antibodies at
      different time intervals after infection in three groups (r100=0.940, r300=0.970,
      r500=0.983, P<0.05). The absorbance value of muscle samples conserved at 4
      degrees C for 7 d and 1 d was the same (0.53) (F=0.250, P>0.05), and those
      conserved at -20 degrees C for 8 wk and 1 wk was 0.46 and 0.50 respectively,
      showing that the antibody level in muscle juice did not decreased considerably
      after the muscle samples were frozen at -20 degrees C for 8 weeks (F=2.273,
      P>0.05). The absorbance value of Trichinella-infected muscle conserved at -20
      degrees C for 10 wk decreased to 0.43, with significant difference from that
      conserved at -20 degrees C for 1 wk, but the positive rate was also 100%, and
      antibodies were detected in all muscle samples conserved at -20 degrees C for 20
      weeks when the experiment was ended. CONCLUSION: When animals died or were
      slaughtered and serum samples could not be collected, muscle juice can be
      collected from fresh, cool and frozen meat and used as a substitute sample for
      detecting anti-Trichinella antibodies.

PMID- 18038771
TI  - [Effectiveness of routinely used assays for the diagnosis of schistosomiasis
      japonica in the field].
AB  - OBJECTIVE: To evaluate the effectiveness of routinely used assays for
      schistosomiasis diagnosis in the field. METHODS: From late November to early
      December 2005, 6-65 years old inhabitants from 3 endemic villages were examined
      by Kato-Katz technique (3 thick smears) and nylon bag sedimentation/hatching
      method. At the same time, dipstick dye immunoassay(DDIA), fast enzyme linked
      immunosorbent assay (F-ELISA), indirect haemagglutination test A (IHA-A) and B (
      IHA-B) were carried out in parallel RESULTS: 1864 people were examined by stool
      examination with an average positive rate of 9.7%. The missing rate of DDIA was
      relatively stable in medium and heavily endemic areas of schistosomiasis. The
      missing rate of nylon bag sedimentation/hatching method was 25% and relatively
      stable when the number of eggs per gram of feces(EPG) was larger than 100. The
      average positive rate of DDIA, F-ELISA, IHA-A and IHA-B was 47.8%, 50.0%, 66.3%
      and 40.1% respectively. Using stool examination as the gold standard, the
      sensitivity of DDIA, F-ELISA, IHA-A and IHA-B was 75.3%, 65.8%, 85.6% and 76.0%;
      and the specificity was 55.1%, 51.7%, 35.7% and 63.6%, respectively. Among the
      four sero-diagnostics, the specificity, Youden index, positive likelihood rate
      and coincidence of IHA-B were the highest. CONCLUSION: Kato-Katz method is more
      stable and effective than nylon bag sedimentation/hatching method in medium and
      heavily endemic areas of schistosomiasis japonica. The sensitivity and
      specificity of these four diagnosis kits are lower than 90%.

PMID- 18038772
TI  - [Potential risks for transmission of schistosomiasis caused by mobile population
      in Shanghai].
AB  - OBJECTIVE: To understand the potential risk for schistosomiasis transmission
      caused by introduction of infection source from mobile population in Shanghai.
      METHODS: Field investigation was conducted in the suburb of Shanghai City by
      screening the mobile population living in Shanghai for more than 1 month and over
      1 years old in a procedure of interviewing, serum indirect hemagglutination (IHA)
      test, and then fecal examination to detect the eggs with nylon sedimentation
      approach for those IHA positives. RESULTS: Among 2,931 mobile people
      investigated, 1,575 were male (53.74%) and 1356 were female(46.26%); 138 out of
      2931 were positive in IHA test (4.71%). 1938 (66.12%) out of 2 931 came from
      Schistosoma japonicum-endemic provinces and its positive rate in mobile
      population (5.99%) was significantly higher than those from the transmission
      interrupted provinces (2.6%) (chi2=10.28, P<0.01), and those from non-endemic
      provinces (1.68%) (chi2=12.86, P<0.01). The 138 IHA positives all showed negative
      in fecal examination. In accordance with the serum positive rate and egg
      infection rate in the national reporting system in 2004, it was estimated that
      there would be about 13 356 and 1 699 potential serum positive cases respectively
      from endemic area and transmission controlled area, and about 2,168 and 255 egg
      positive cases from the two kind areas respectively, majority of the cases were
      from Anhui Province. CONCLUSION: Schistosomiasis transmission risks potentially
      exist in Shanghai suburb due to the introduction of infected mobile people from
      other endemic provinces, and a surveillance system and quick response are needed
      for the possible re-emergence of the disease.

PMID- 18038773
TI  - [Apoptosis of human leukemia K562 cell in vitro induced by Toxoplasma gondii].
AB  - OBJECTIVE: To investigate whether the Toxoplasma gondii can inhibit proliferation
      of human leukemia K562 cells and/or induce apoptosis of the cells in vitro.
      Methods K562 cells (5x10(4)/ml) were harvested at mid-exponential phase and
      planted in 96 well plates with 100 microl each and in 50 ml culture bottles, 1.5
      ml each. The cells were treated for 48 hours with different concentration of
      Toxoplasma tachyzoites. Growth inhibition rate was measured with MTT method.
      Apoptosis was detected through following ways: fluorescence microscopy with
      Hoechst 33 258 staining was used for observing the change of cell morphology,
      agarose electrophoresis was used to detect the DNA changes and FCM was used to
      observe sub-diploid. RESULTS: Toxoplasma can inhibit proliferation of K562 cells.
      K562 cells treated with Toxoplasma presented an inhibition rate of 17%, 28%, 48%,
      50% and 55% under the tachyzoite concentration of lxl0(4), 2x10(4), 4x 10(4),
      8x10(4) and 16xl0(4)/ml respectively, with a significant difference to the
      control (t=3.606, 5.918, P<0.05; t=9.171, 7.841 and 7.067, P<0.01). Cell
      contraction and apoptotic bodies were observed under fluorescence microscope. DNA
      fragment was shown through agarose electrophoresis. Flow cytometric analysis
      showed an apoptosis peak at 48h. The apoptosis rate was 5.53%, 7.12%, 10.34%,
      21.14% and 29.68% respectively. CONCLUSION: Toxoplasma gondii inhibits
      proliferation and induces cell apoptosis in K562 cells in vitro.

PMID- 18038774
TI  - [Changes of CD4+CD25+ T cells in the spleen of mice infected with Toxoplasma
      gondii].
AB  - OBJECTIVE: To observe the changes of CD4+CD25+ regulatory T cells in the spleen
      of mice infected with T.gondii. METHODS: Twenty-eight female C57BL/6 mice were
      randomly divided into four groups. Three groups of mice were inoculated
      intraperitoneally with 10(4) tachyzoites in 200 microl sterile PBS. At 2, 4 and 6
      days post-infection, the spleens were removed. The expression level of Foxp3 mRNA
      in splenic CD4+ T cells was quantitated by real-time PCR. The percentage of
      CD4+CD25+ regulatory T cells in CD4+ T cells was determined by flow cytometry,
      and the absolute numbers of splenic CD4+CD25 - regulatory T cells and CD4+ T
      cells were assessed. The fourth group was injected intraperitoneally with 200
      microl sterile PBS as control. RESULTS: The relative mRNA level of Foxp3 in
      splenic CD4+ T cells at day 4 (1.89+/-0.23) and day 6 (1.79+/-0.24) post
      infection was significantly higher than control (1.00+/-0.12) (P< 0.01). After an
      initial up-regulation at 2 days post-infection (15.07%+/-2.73%) (P<0.05), the
      proportion of CD4+CD25+ regulatory T cells in CD4+ T cells at day 4 (24.29%+/
      3.19%) and day 6 (19.80%+/-2.66%) post-infection was significantly higher than
      control (11.58%+/-2.04%) (P<0.01). At day 6 post-infection, both the percentage
      of splenic CD4+ T cells in splenocytes(5.49%+/-l.71%) and absolute number of CD4+
      T cells (1.71+/-0.44)x106 greatly decreased(P<0.01). CONCLUSION: The proportion
      of splenic CD4+CD25+ regulatory T cells in CD4+ T cells has been up-regulated
      following T. gondii infection, which is mainly due to a great reduction of CD4+ T
      cells in the spleen.

PMID- 18038775
TI  - [Production and identification of chicken egg yolk antibodies against soluble egg
      antigen of Schistosoma japonicum].
AB  - OBJECTIVE: To produce and purify egg yolk immunoglobulin against soluble egg
      antigen (SEA) of Schistosoma japonicum, and evaluate its specificity and
      sensitivity. METHODS: 25-week old hen was intravenously and subcutaneously
      immunized with SEA of Schistosoma japonicum for 4 times. Each hen was first
      immunized with 60 microg SEA and subsequent injections were performed at 10-day
      intervals with 30 microg SEA. IgY was extracted from eggs of hen 35 d after the
      first inoculation by WD (water-dilution) method, eggs from non-immunized hen were
      used as negative control. The protein concentration of IgY was measured by BCA
      method, and IgY was analyzed by SDS-PAGE and Western blotting. SEA-based ELISA
      was used to evaluate the specificity and sensitivity of the IgY. RESULTS: 61 mg
      IgY was extracted from one egg. The results of SDS-PAGE and Western blotting
      demonstrated that the IgY contained one major protein band with molecular weight
      of 130,000 and could be recognized by SEA. Specific IgY could be immediately
      detected by SDS-PAGE and ELISA in the eggs laid by the hens from 10 days after
      the first immunization. On day 31 after the primary immunization, the antibody
      titer reached 1:1 600. 2.4 ng/ml SEA was detected by IgY based-sandwich ELISA,
      which indicated a high sensitivity of the purified IgY. CONCLUSION: Anti-SEA IgY
      with high specificity and sensitivity has been obtained and purified.

PMID- 18038776
TI  - [Ciliated protozoan in sputum of a pneumonia patient].

PMID- 18038777
TI  - [Enzyme histochemistry: the effect of META-Li on Oncomelania hupensis].
AB  - OBJECTIVE: To explore the killing mechanism of META-Li against Oncomelania
      hupensis by observing the change of enzyme activity in snail tissue. METHODS:
      Sixty snails were divided into 2 groups. Snails in experiment group were immersed
      in META-Li (100 mg/L) for 2d and soft tissue was separated for frozen sections.
      Histochemical staining for the enzymes CCO, LDH, SDH, AChE and NOS was done by
      routine method and the average grey density was measured under microscopy. Tissue
      sections of 10 snails were used to detect grey density for each enzyme. Snails
      without META-Li treatment served as control. RESULTS: The enzyme activity of CCO
      and AChE in the experiment group was significantly lower than that in the control
      (t=12.26, P<0.01), that of LDH and NOS in the experiment group was significantly
      higher than that in the control (t=3.41, P<0.05). There was no significant
      difference on the enzyme activity of SDH between the two groups (t=0.51, P>0.05).
      CONCLUSION: The snail-killing effect of META-Li may be relevant to the enzyme
      activity in energy metabolism and the blocking of the nerve transmission.

PMID- 18038778
TI  - [Bioinformatics analysis for the structure and function of lactate dehydrogenase
      from Schistosoma japonicum].
AB  - OBJECTIVE: To predict the structure and function of SjLDH using bioinformatics
      method. METHODS: By online analysis at bioinformatics websites such as NCBI
      (http://www.ncbi.nlm.nih.gov/) and Expasy (http://cn.expasy. org/), and employing
      software packages such as Vector NTI suite and PCgene to do multi-sequence
      homological alignment, phylogenetic analysis, secondary structure and topological
      prediction, homology modeling of tertiary structure, antigenic epitope analysis,
      etc. RESULTS: Same conservative sites and key catalytic sites existed among SjLDH
      and LDHs from other species. Similarity of SjLDH compared to CsLDH, TvLDH and
      HsLDH was 75%, 17%, 58%-60% respectively. Phylogenetic analysis demonstrated that
      the evolution relation between SjLDH and DmLDH was closer than the relation
      between SjLDH and CeLDH, the relationship between SjLDH and HsLDH-B, -C was
      closer than HsLDH-A. Three transmembrane regions were found, the region of 98aa
      106aa in three hydrophilic regions located outside of membrane was inferred as
      the major antigen epitope. This antigen epitope had significant difference with
      LDHs from protozoon (Pf., Tg., Tv.) and had 1-3 amino acid residue difference
      with MmLDH, HsLDH-A, -B, -C, and was the same with CsLDH. One of the key
      catalytic residues and substrate (pyruvate) binding loop were located in this
      region. Tertiary structure demonstrated that 98aa-106aa was on the surface of the
      protein and formed a substrate binding loop, other two key catalytic sites were
      at the position near the loop. CONCLUSION: The prediction implied that LDH was an
      ideal molecule for phylogenetic analysis; SjLDH might be a potential molecular
      target for immunodiagnosis, anti-schistosome drug and vaccine development.

PMID- 18038779
TI  - [In vitro observation on effect of nitric oxide on exflagellation of Plasmodium
      yoelii].
AB  - OBJECTIVE: To observe the effect of nitric oxide (NO) on exflagellation of
      malaria parasite. METHODS: The level of parasitemia and gametocytaemia in DBA/2
      mice infected with Plasmodium yoelii 17XL was measured by scanning Giemsa-stained
      blood smears, and the NO level in culture supernatant of splenocytes was checked
      using Griess reaction. The mice were injected with different doses of NO donor
      (NOC5) on day 4 post-infection, and control mice were injected with NOC5
      precursor. On day 6 post-infection, mice were injected with NOS inhibitor (L
      NMMA), and control mice were injected with D-NMMA and PBS, respectively. Blood
      samples were collected from tail vein of mice before injection, 30 and 60 min
      after being injected with NOC5 and NOC5 precursor, 4 and 8 h after being injected
      with L-NMMA, D-NMMA, and PBS respectively. Exflagellation number of gametocytes
      in blood culture was counted under microscope. Results The NO level in culture
      supernatant of splenocytes from mice on day 4 and 6 post-infection was 16.5
      mmol/L and 30.4 mmol/L, and exflagellation number was 11.33 and 0.66,
      respectively. The number of exflagellation in parasitized erythrocytes, obtained
      from mice on day 4 post-infection, was 5.33 and 2.66, respectively, 30 and 60 min
      after injection of 1 mg NO donor (NOC5), significantly lower than that of the
      control (P<0.01). The number of exflagellation in parasitized erythrocytes
      derived from mice on day 6 post-infection was 1.83, 8 h after the injection of
      NOS inhibitor (L-NMMA), which was significantly higher than that of the control
      (P<0.01). CONCLUSION: NO is a major effector molecule resulting in natural
      transmission-blocking of malaria parasite by directly inhibiting exflagellation
      of male gametocytes.

PMID- 18038780
TI  - [Study on the variation of lymphocytes and cytokines in patients with
      echinococcosis granulosus].
AB  - OBJECTIVE: To investigate the variation of lymphocytes and cytokines in patients
      with cystic echinococcosis (CE). METHODS: 80 CE patients who were diagnosed for
      the first time (60 of Han and 20 of Uygur nationality), and 37 patients who were
      to accept the second surgical operation(24 Han and 13 Uygur nationality) were
      included in the study. The peripheral lymphocytes of patients before operation
      were analyzed by flow cytometry (FCM) to detect T and B lymphocytes, NK cells
      bearing surface markers, as well as Thl cytokine IFN-gamma and Th2 cytokine IL-4
      in the cytoplasm of lymphocytes. 179 healthy persons served as control. RESULTS:
      In the group of Han patients who were diagnosed for the first time, the
      percentage of total T cells(CD3+) was lower than the control (P<0.05), while
      among patients accepting the second operation, the ratio of total T cells showed
      no difference to the control. For the helper T cells (CD3+/CD4+), NK cells
      (CD3+/CD16,56+) and B cells (CD3+/CD19+), their ratio were significantly lower in
      both groups than the control (P<0.01), but their cytotoxic T cells (CD3+/CD8+)
      were higher than the control. In Uygur patients diagnosed for the first time, B
      cell ratio was lower than that in control (P<0.05). The NK cell level in both
      groups of patients was lower than control (P<0.01 and P<0.05 respectively). The
      level of ThO and Th1 showed no statistical difference among the three groups
      (P>0.05). The Th2 level was significantly higher in the first diagnosed patients
      than control (P<0.01), but no statistical difference between the group with the
      second operation and the other two groups. CONCLUSION: The immune status of
      echinococcosis patients is inhibited and the level of Th1 and Th2 shows
      difference in the first and second operation groups.

PMID- 18038781
TI  - [Sensitivity, specificity and stability of the Tag-primer nested/multiplex PCR
      for malaria diagnosis].
AB  - OBJECTIVE: To improve the sensitivity, specificity and stability of the Tag
      primer nested/multiplex PCR for malaria diagnosis. METHODS: Filter paper blood
      samples were collected from 30 non-malaria fever patients and 20 infectious
      disease patients (common cold, influenza, typhoid, hepatitis, etc.). Four ml
      blood each taken from one falciparum malaria patient and one vivax malaria
      patient was serially diluted. Healthy blood sample was used as negative control.
      Improved direct heating method was used to prepare DNA template. The cytochrome
      oxidase gene (coxI) located in mitochondrion was selected as target gene.
      Relevant web resources and software (PUBMED, NCBI-BLAST, Mfold server and Primer
      Premier 5.0) were employed to design and optimize Tag-primer nested/multiplex PCR
      (UT-PCR) which was used to test all blood samples. RESULTS: A 611 bp band and a
      255 bp band were seen in serially diluted infected blood samples (1,000, 100, 10
      and 1 parasite/microl) from P.f and P.v patient tested by UT-PCR. The detection
      limit of either P. falciparum or P. vivax reached 1 parasite/microl, and the
      tested blood samples of non-malaria fever patients, patients with other
      infectious diseases and healthy persons were all negative. Consistent results of
      each sample in more than 3 duplicated tests were obtained. CONCLUSION: The
      optimized Tag-primer nested/multiplex PCR shows high sensitivity, specificity and
      stability in malaria diagnosis.

PMID- 18038783
TI  - [Study on 5S rDNA sequence of two isolates of Trichinella from Guangxi].
AB  - OBJECTIVE: To analyze 5S ribosomal DNA (5S rDNA) sequences of two Trichinella
      isolates from Guangxi. METHODS: The fragments of 5S rDNA were obtained by PCR
      from the isolates of Debao and Nandan, and sequencing was made for the PCR
      products. Homogeneity, genetic distance matrix and phylogenetic tree were
      analyzed by related software. 5S rDNA sequences of the two isolates were compared
      separately with those of Trichinella species in GenBank. RESULTS: 5S rDNA
      sequences of three Trichinella isolates (Debao, Nandan and T. spiralis) showed
      the same length at 695 bp. There were 4 variable positions. The homogeneities of
      Debao and Nandan isolates with T. spiralis were 99.0% and 99.1% respectively. The
      homogeneities between Debao isolate and Nandan isolate was 98.8%. Compared with
      other Trichinella isolates in GenBank, they were all less than 94.2%. The
      evolutionary distance among isolates of Debao and Nandan and T. spiralis was
      0.014. Meanwhile, the evolutionary distances between the Guangxi isolates and
      other Trichinella isolates in GenBank were more than 0.056. Phylogenetic tree
      analysis revealed that two isolates of Guangxi and T. spiralis located at the
      same node, revealing a close relationship. Bootstrap confidence values in two
      phylogenetic trees were 96 and 99, respectively. CONCLUSION: The two Trichinella
      isolates of Guangxi show a high homogeneity with T. spiralis, locate at the same
      nodes in phylogenetic tree,suggesting that the Debao and Nandan Trichinella
      isolates be identified as T. spiralis.

PMID- 18038782
TI  - [Study on immuno-effect with GRA4 or SAG2 gene recombinant BCG vaccine of
      Toxoplasma gondii].
AB  - OBJECTIVE: To compare the immuno-protection induced by the recombinant BCG
      vaccine of Toxoplasma gondii GRA4 gene (rBCG-GRA4) and SAG2 gene (rBCG-SAG2) in
      BALB/c mice. METHODS: 108 SPF BALB/c mice were divided into 6 groups: PBS, BCG,
      rBCG, rBCG-GRA4, rBCG-SAG2 and rBCG-GRA4+SAG2, each with 18 mice. Each mouse was
      injected by 100 microl corresponding materials for 2 times. Blood was taken from
      tail vein before inoculation. 4,6 and 8 weeks after inoculation, spleen was moved
      and blood was taken from orbit vein of 3 mice from each group for the detection
      of cytokines, IgG and IgM antibodies, T lymphocyte subgroups and transformation
      efficiency. 3 weeks after the last inoculation, 9 mice from each group were
      challenged intraperitoneally with 50 tachyzoites of T. gondii RH strain and their
      survival time was observed. RESULTS: rBCG vaccine of T. gondii induced immune
      response. The value of CD3+ CD4+/CD3+CD8+ of group BCG-GRA4+SAG2 was the highest
      (14.06+/-1.17) in the 4th week; the IgG titer in the BCG-GRA4+SAG2 group was the
      highest (0.18+/-0.02) in the 6th week and the IgM titer in the BCG-SAG2 group was
      the highest (0.82+/-0.05) in the 8th week. The average survival time of the mice
      in BCG-SAG2 group was about 8.61 days after challenged with tachyzoites, and that
      of the PBS control group, 7.33 days. The average survival time in the 3 immunized
      groups was one day longer than that of the control. CONCLUSION: The rBCG vaccine
      of T. gondii shows certain immuno-protection in mice.

PMID- 18038784
TI  - [Factors affecting malaria outbreak in Congjiang county of Guizhou Province].
AB  - OBJECTIVE: To make a field investigation on the affecting factors of malaria
      outbreak in a village of Congjiang County, Guizhou Province. METHODS: The
      investigation was made in August, 2006. Filter paper dry blood samples were taken
      for indirect fluorescent antibody test (IFAT) from all the 495 residents above 1
      year-old in the village where an outbreak of malaria was reported.
      Questionnairing was conducted in 423 villagers over 10 years-old, covering
      malaria history in the past 2 years, knowledge on malaria and its control, use of
      mosquito nets, and out-door sleeping habit. Data on febrile outpatients were
      collected from the records of the township health center for analyzing the
      compliance of the patients in seeking medical services. Mosquito collecting by
      human-bait before mid-night, and in mosquito nets and cattle pens in early
      morning was performed for mosquito composition and man-biting rate. RESULTS: Re
      examination of the 42 positive blood smears confirmed 12 positives of P. vivax
      infection. The malaria incidence in 18 d was 2.1%, including 4 cases clinically
      diagnosed. The antibody positive rate of IFAT in the population was 8.7% (43/495)
      with a positive GMRT of 20.6, overall GMRT of 10.6; the IFAT positive rate in the
      age group of under 5 was 7.5% (3/40) with a GMRT of 25.1. The rate of seeking
      medical advice among febrile patients was 81.3% (118/145), 78.8% (93/118) of
      which being in the village clinic. The average time of going to a doctor after
      fever was 3.9 days, 37.4% (195/521) and 3.3% (17/521) were in 4-6 days and over
      10 days respectively, with the longest 26 days. The average knowledge rate on
      malaria was 25.5% (108/423), with 17.1%, 29.2% and 40.0% in the groups of
      illiteracy, primary school and high school education respectively. A statistical
      significance was found between primary school/high school education and the
      illiteracy (P<0.01). The average rate of using mosquito nets was 31.0% (131/423),
      out-door sleeping rate was40.7% (172/423). The radical cure rate in 2004 and 2005
      was 68.2% (15/22) and 48.3% (14/29) respectively. In addition to Anopheles
      sinensis, An. anthropophagus and An. minimus also existed in rooms and nets with
      a man-biting rate of 0.0566 and 0.0755 respectively. CONCLUSIONS: Three species
      of anopheline mosquitoes are the important transmitting vectors. Poor self
      protection, outdoor sleeping habit, delayed examination and treatment, and
      irregular chemotherapy among the residents are the main factors resulting malaria
      outbreak.

PMID- 18038785
TI  - [An epidemiological survey on echinococcosis in Zhiduo County of Qinghai
      Province].
AB  - The survey was carried out in July, 2006 in Zhiduo County. The IHA and ELISA
      positive rate in human population was 4.5% (42/933) and 8.2% (76/931)
      respectively. Ultrasonography revealed a morbidity of 3.4% (33/979) with 3.2%
      Echinococcus granulosus and 0.2% of E. multilocularis respectively. Animal
      dissection showed an infection rate of 15.1% (14/93) in pikas with one infected
      by E. shiquicus proved by molecular biology. Coproantigen rate by ELISA was 62%
      (12/193) in dogs and 35.7% (5/14) in wolves. The results indicated that Zhiduo
      County is a mixed endemic area for echinococcosis.

PMID- 18038786
TI  - [Study on the feasibility for ARIMA model application to predict malaria
      incidence in an unstable malaria area].
AB  - OBJECTIVE: To explore the application of seasonal time series ARIMA model in
      prediction of malaria incidence in an unstable malaria area. METHODS: SPSS13.0
      software was used to construct the ARIMA model based on the monthly malaria
      incidence of Huaiyuan and Tongbai counties in Huaihe River Valley, from Jan. 1998
      to Dec. 2005, with consideration of residual un-correlation and conclusion.
      Akaike's information criterion (AIC) and Bayesian information criterion (BIC)
      were used to confirm the fitness of model. The constructed model was then applied
      to predict the monthly malaria incidence in 2006 and the incidence from ARIMA
      model was compared with the actual incidence, so as to evaluate the model's
      validity. Malaria incidence of 2007 was predicted by ARIMA model based on malaria
      incidence from 1998 to 2006. RESULTS: Statistics assisted estimation of the
      significance of the fitted autoregressive and seasonal moving average
      coefficients (AR1=0.512, SMA1=0.609, P<0.01). ARIMA (1,0,0)(0,1,1)12 model, with
      AIC=67.01, BIC= 71.87 and white noise for predicting error, exactly fitted the
      incidence of the previous monthly incidence from Jan. 1998 to Dec. 2005, and the
      predicted monthly incidence in 2006 by the model was consistent with the actual
      incidence. Malaria incidence of 2007 would be 106.50/100 000, with a peak
      incidence during July and October. CONCLUSION: The model of ARIMA seems to be an
      appropriate model to fit exactly the changes of malaria incidence and to predict
      the future incidence trend, with a high prediction precision of short term time
      series.

PMID- 18038787
TI  - [Malaria complicated with HIV infection: 9 cases].

PMID- 18038788
TI  - [Application of reverse vaccinology in Schistosoma vaccine development: advances
      and prospects].
AB  - OBJECTIVE: Current advances in reverse vaccinology based on the principle of
      "sequence-structure-function" and such integrated platform technologies as
      immunoinformatics, computer-aid design, and various high-throughput omics
      (including genomics, transcriptomics and proteomics) may pave a new way for the
      discovery of candidate vaccine molecules against schistosomiasis. Both
      theoretical prediction and experimental approaches conventionally used in the
      field of reverse vaccinology are briefly introduced in this review; and the
      applications of these approaches to screening and confirming candidate
      Schistosoma vaccine molecules are also summarized. Furthermore, potential
      research prospects of the application of reverse vaccinology to Schistosoma
      vaccine development are discussed by simulating immune effect mechanisms of
      immunization with radiation-attenuated cercaria vaccine in animal hosts and
      naturally acquired immunity in human population.

PMID- 18038789
TI  - [An analysis on papers published by the National Institute of Parasitic Diseases
      in 2002-2006].
AB  - OBJECTIVE: To partially evaluate the scientific and technological activities of
      the Institute of Parasitic Diseases, China CDC, through publication analysis.
      METHODS: Information on the papers published in the last 5 years was collected
      since the renaming of the Institute in 2002. Number, category and being cited
      frequency of the publications were analyzed using the data of 2002 as baseline.
      RESULTS: 272 papers were published at 48 national and international periodicals
      during 2002-2006. The total number, the number of papers published at the core
      journals and at the SCI journals all increased in the year 2003-2006.
      Publications on research, review and report occupied 54.8%, 36.0% and 15.4%
      respectively, covered schistosomiasis, malaria, echinococcosis, filariasis,
      visceral leishmaniasis, food-borne and soil-transmitted parasitic infections, and
      newly emerging parasites with 44.5% and 15.4% on schistosomiasis and malaria
      respectively. 87.9%, 11.0% and 1.1% of the articles were published at the
      national, international and local journals respectively. The balance rate for the
      trends of papers submitted in 2002 was 6.5%, and 10.2%-15.4% in 2003-2006. 34 of
      the 272 papers were included in SCI journals. Retrieval through the web of
      knowledge revealed that 187 citations were found in the SCI papers with an
      average of 5.5; 6 papers were cited for more than 9 times each, occupying 27.3%
      of the overall citations, the highest being 84 citations. There was an unbalanced
      distribution of the publications among the departments of the Institute.
      CONCLUSION: The results indicate that the research direction and content are in
      line with the tasks of the Institute and with the scientific merits of disease
      control; the level of research is increasing and some of the publications exert
      certain impact at home and abroad.

PMID- 18038790
TI  - [Construction of eukaryotic expression plasmids with paramyosin gene of periodic
      Brugia malayi].
AB  - Total RNA was extracted from periodic Brugia malayi Specific primers were
      designed on the basis of known sequences of paramyosin gene from B. malayi
      (BmPmy). The desired gene was amplified by PCR technique from cDNA. The PCR
      products were purified and cloned into plasmid pGEM-T by T-A cloning method,
      transformed into Escherichia coli (E. coli) strain DH5alpha. The recombinant
      plasmids were screened and identified by digestion with restriction enzyme and
      PCR amplification. The right gene fragments encoding BmPmy in positive clones for
      prokaryotic and eukaryotic expression plasmids were digested with restrictive
      endonuclease, and were subcloned into pcDNA3.1(+). The recombinant eukaryotic
      plasmid (pcDNA3.1-BmPmy) was then transfected into COS-7 cells. The transient
      expression of BmPmy was examined with RT-PCR. BmPmy mRNA was highly expressed in
      transfected COS-7 cells.

PMID- 18038791
TI  - [Comparative study on polytene chromosomes of two isolates of Simulium
      quinquestriatus].
AB  - The salivary glands were exposed and isolated from the larvae of Simulium
      quinquestriatus and stained in carbol fuchsin, squashed between slide and
      coverslide. Slides were examined and photographed under microscope to measure the
      polytene chromosomes. Systematic analysis was made. Results indicated that the
      number of the polytene chromosomes of both isolates is three. The main
      characteristic chromosomal structures are homologized. Only the banding types of
      II L are different.

PMID- 18038792
TI  - [Dot enzyme-linked immunosorbent assay for detection of serum antibody to
      Blastocystis hominis in humans].
AB  - Serum and stool samples were collected from 322 undergraduate students in medical
      school. Using stool in vitro cultivation as golden standard, 178 cases were found
      Blastocystis hominis positive and 144 were negative. Dot-ELISA was used to
      examine the serum samples with a sensitivity of 92.1% (164/178) and specificity
      of 97.1% (141/144). This revealed that dot-ELISA can be used for antibody
      detection against Blastocystis hominis.

PMID- 18038793
TI  - [Malaria epidemic situation in Jiangsu Province in 2006].
AB  - In 2006, there were 767 reported malaria cases in Jiangsu Province with an
      incidence of 1.07 per thousand and increased by 16.57% in comparison to the
      previous year. Positive rate of blood examination in local febrile patients was
      0.08% (293/361 896) but 1.23% (251/204 40) in mobile population (P<0.01). Cases
      with relapses occupied 9.00% of the total. The density of Anopheles sinensis was
      0.61 per net and increased by 110% more than the year 2005 (0.29/net). It is
      indicated that the increase of A. sinensis density has been the main factor for
      malaria recurrence in the area north of Huaihe River in the Province.

PMID- 18038794
TI  - [Historical review on the development of medical parasitology in China during the
      years of 1871-2006].
AB  - The present review deals with the representative research papers on human
      parasites and parasitic diseases in China over the past hundred years (1871
      2006). As the views focused on the development of the medical parasitology, the
      historical background and progressive characters in the period of fermentation,
      origination, and expansion have been discussed. The check list of the first cases
      of human parasitic diseases reported in China during 1871-2006 contained 128
      species of parasitic pathogens, and among them 38 species were the newly
      revisional records. The citation from Faust's paper (1923) proved that previous
      record of "the first case of Eurytrema pancreaticum from Hongkong" was an
      absurdly mistake. The human infections of Diphyllobothrium latum, Toxocara canis,
      and Triodontophorus minor discovered by Lin (1924) from Beijing were the first
      records in the country. A doubtful malaria case reported from Chongqing by Hung
      (1944) should be revised as the first case of babesiosis in China. The above
      presented examples suggest that the truthful record of parasitic pathogens is an
      important base for the discovery history of parasitic diseases. With comments on
      the research progress of human parasitic diseases in different historical stages,
      it seems that the trends of medical parasitology development in China have been
      synchronous with the research activities in the area.

PMID- 18038795
TI  - [Preparation of five ginkgolic acid monomers and their molluscicidal effects
      against Oncomelania hupensis].
AB  - OBJECTIVE: To investigate the molluscicidal activities of the ginkgolic acid(GA)
      monomers isolated and purified from GAs. METHODS: Five monomers of GAs from the
      sarcotesta of Ginkgo biloba. were extracted by petrol ether, separated by silica
      gel column chromatography, purified by semi-prepared reversed-phased HPLC, and
      identified by LC-MS analysis. The molluscicidal activities of GAs and their
      monomers against Oncomelania hupensis were determined as referring to the WHO
      guidelines for laboratory molluscicidal test. RESULTS: The five purified
      ginkgolic acid monomers were GA(13:0), GA(15:0), GA(15:1), GA(17:1) and GA(17:2),
      with a side chain of 13, 15, 17 alkyl or ethylenic radicals res pectively on
      their benzene loop. The five monomer proportions to the total GAs were 17.6%,
      3.2%, 52.3%, 23.3% and 3.6% respectively. The order of molluscicidal activities
      for the five monomers was as follows:
      GA(13:0)>GA(15:1)>GA(15:0)>GA(17:1)>GA(17:2), and their LC50 for snails was 20.79
      mg/L, 22.28 mg/L, 33.76 mg/L, 51.89 mg/L, and 59.10 mg/L respectively after
      immersion for 24 hours. Two monomers, GA(13:0), and GA(15:1) inhibited the
      snails' climbing up significantly. CONCLUSION: The molluscicidal activities of
      GAs may be dependent on the monomer's structure with different number of carbon
      molecules and double-bonds on the side carbon-chain. The two monomers, GA(13:0)
      and GA(15:1), are mainly responsible for the molluscicidal activities of GAs and
      both effectively inhibit snails' climbing up as well. GA(15:0) also shows certain
      molluscicidal activity.

PMID- 18038797
TI  - [Development and identification of the multiple B cell epitope antigens of
      Schistosoma japonicum].
AB  - OBJECTIVE: To develop multiple B cell epitope antigens of Schistosoma japonicum
      and evaluate their antigenicity. METHODS: Bioinformatics software BioSun was used
      to predict B cell epitopes from Sj22.6, Sj14-3-3 and Sj26. The predicted epitopes
      P2, P6 and P7 were ligated to construct P2-P6-P7 and P6-P2-P7 multiepitope in
      random order, a 6 amino acid linker inserted between epitopes. Recombinant
      plasmids containing the two multiepitopes identified by enzyme digestion and
      sequencing were transformed into E. coli BL21. The expressed recombinant fusion
      proteins of E. coli BL21 induced with IPTG were purified with Ni2+ chelating
      HiTrap HP column. Their antigenicity was evaluated with Western-blotting. RESULT:
      The two multiple B cell epitopes P2-P6-P7 and P6-P2-P7 were successfully cloned
      into pET-32c(+) plasmid and fusion proteins were expressed. SDS-PAGE showed a
      single band and both of the recombinant fusion proteins were with Mr 20 400. The
      two proteins reacted with the sera of schistosomiasis patients but not with that
      of healthy people. CONCLUSION: Two multiple B cell epitope antigens were
      developed with potential diagnosis value.

PMID- 18038796
TI  - [The cleavage activity of GCV transfer vector-mediated hammerhead ribozyme for
      KRR1 in vitro transcript].
AB  - OBJECTIVE: To detect the cleavage activity of Giardia canis virus (GCV) transfer
      vector-mediated hammerhead ribozyme for KRR1 in vitro transcript. METHODS:
      Giardia, a most primitive eukaryote, has KRR1 protein responsible for ribosome
      biosynthesis. cDNA encoding hammerhead ribozyme flanked with various lengths of
      antisense RNA was cloned into a viral vector pGCV634/GFP/GCV2174 derived from the
      genome of GCV, KRzS flanked with 21 nt KRR1 antisense RNA on each arm, or KRzL
      flanked with 288 nt and 507 nt KRR1 antisense RNA. At the same time, two control
      groups were established: PKR without the inserted ribozyme, and TRzL flanked with
      324 nt and 380 nt triosephosphate isomerase (Tim) antisense RNA. The cleavage
      activity of GCV transfer vector-mediated hammerhead ribozyme for KRR1 in vitro
      transcript was then analyzed by absolute real-time quantitative RT-PCR. RESULTS:
      The in vitro cleavage activities on KRR1 mRNA of the two ribozyme KRzS or KRzL
      were 74.0% and 81.1% respectively by the absolute real-time quantitative RT-PCR.
      The two control groups, PKR or TRzL, showed no effect on KRR1 mRNA in vitro.
      CONCLUSION: The GCV transfer vector-mediated hammerhead ribozyme shows a high
      cleavage activity for KRR1 in vitro transcript, which demonstrates the
      feasibility of using a viral vector to express a ribozyme targeted at a specific
      mRNA in Giardia to reduce the expression of a specific gene.

PMID- 18038798
TI  - [Intranasal immunization with mucosal complex vaccine protects mice against
      Toxoplasma gondii].
AB  - OBJECTIVE: To study the mucosal and systemic immune response after intranasal
      immunization with mucosal complex vaccine for Toxoplasma gondii, and to observe
      the protective effect on mice. METHODS: The mucosal complex vaccine was made of
      soluble tachyzoite antigen (STAg) and cholera toxin (CT), which were mixed and
      dissolved in PBS (1 ml PBS containing 1 mg STAg and 50 microg CT). Fifty-two
      BALB/c mice were randomly divided into two groups: immunized group and control.
      Mice were intranasally immunized with 20 microl mucosal complex vaccine (20
      microg STAg and l microg CT) per mouse twice at an interval of two weeks, while
      the control mice were given PBS solution instead. Six mice of each group were
      killed by dislocation of cervical vertebra on day 14 after the last immunization.
      The specific IgG antibodies in serum and IgA in feces were detected by ELISA.
      Lymphocytes in spleen, Peyer's patches (PP) and intestinal intraepithelial
      lymphocyte (IEL) were isolated and counted. Percentage of CD4+ and CD8+ T cells
      was determined by immunocytochemistry. Other mice were challenged
      intragastrically each with 4 x 10(4) tachyzoites of RH strain Toxoplasma gondii
      on day 14 after the last immunization. Their health condition was observed and
      the number of tachyzoites in liver and brain was determined microscopically on
      the 30 th day after challenge. RESULTS: IgG antibodies in serum and IgA
      antibodies in feces of immunized mice were higher than the control (P < 0.05).
      Lymphocytes in spleen, PP and IEL significantly increased after immunization (P <
      0.01). The CD4+ and CD8+ T cells were both higher than that of the control (P <
      0.05) in spleen and PP. The number of CD8+ T cells in IEL increased significantly
      (P < 0.01), and the ratio of CD4+ and CD8+ T cells was reversed with significance
      (P < 0.05). On the day 30 after challenge, the survival rate of immunized mice
      was higher than that of control (P < 0.05), while the tachyzoite load in liver
      and brain was significantly smaller respectively. CONCLUSION: Intranasal
      inoculation with mucosal complex vaccine effectively induces the mucosal and
      systemic immune response, and protects mice against Toxoplasma gondii.

PMID- 18038799
TI  - [Cloning and expression of a bradyzoite-specific gene of Toxoplasma gondii and
      immunoreactive analysis on the recombinant antigen].
AB  - OBJECTIVE: To clone and express bradyzoite antigen 1 (BAG1) gene of T. gondii,
      and analyze the immunoreactivity of the recombinant product. METHODS: The
      differentiation of T. gondii RH strain tachyzoites into bradyzoites was induced
      in vitro, and the coding sequence of BAG1 was amplified from bradyzoites by RT
      PCR. The PCR product was analyzed by sequencing. The BAG1 coding sequence was
      further subcloned into the plasmid pET32a(+). The plasmid pET32a(+) -BAG1 was
      then transformed into BL21(DE3) to express after IPTG induction. The expression
      product was purified with Ni-NTA agarose and the purified BAG1 was further
      analyzed by Western blotting and ELISA. RESULTS: BAG1 cDNA was amplified from
      bradyzoites. After IPTG induction, BAG1 was expressed in a fusional form in E.
      coli. Western blotting showed that the purified recombinant protein could be
      specifically recognized by sera from mice chronically infected by T. gondii B36
      strain. ELISA showed that the positive rate of T. gondii IgG antibodies of 350
      human sera detected by the recombinant BAG1 (17.4%) was higher than by
      recombinant SAGI (12.6%) (P < 0.05). CONCLUSION: The expressed recombinant BAG1
      shows a specific immunoreactivity.

PMID- 18038800
TI  - [Enzyme change in bronchoalveolar lavage fluid of pneumocystis pneumonia rats and
      the effect of garlicin treatment].
AB  - OBJECTIVE: To study the change of enzymes and effect of garlicin treatment on the
      change in bronchoalveolar lavage fluid (BALF) of rats with Pneumocystis carinii
      pneumonia (PCP). METHODS: Wistar rats were injected intramuscularly continually
      with dexamethasone to establish the rat model of PCP. The experimental rats
      (group A) were injected intramuscularly with garlicin at a dose of 10 mg/(kg x d)
      for 5 days in the 3rd, 6th and 9th week respectively, and SMZ/TMP therapy group
      (B), PCP infected group (C) and normal group (D) were established as controls.
      Three days after the last treatment, the rats of all groups were killed and BALF
      was collected without contamination and enzymes AST, ALF, CHE, ALP, LDH, CK,
      CKMB, HBDH, AFU, 5'NT, ADA were examined. RESULTS: The ALP level in group C
      [(573.41 +/- 350.63)U/L] was significantly higher than that in group D [(210.56
      +/- 114.41) U/L] (q = 4.682, P < 0.01), group A [(392.07 +/- 217.57) U/L] (q =
      3.851, P < 0.05), and group B [(325.21 +/- 180.65) U/L] (q = 4.380, P < 0.01);
      the level of CK, CKMB and 5'NT in group C [948.94 +/- 403.43, 489.47 +/- 254.46
      and (6.76 +/- 3.11) U/L respectively] was higher than those in group D [426.22 +/
      319.00, 213.33 +/- 144.54 and (3.22 +/- 1.20) U/L] (q = 4.696, 3.784, 3.812, P<
      0.05); there was no significant difference in the level of AST, ALT, CHE, LDH,
      HBDH, AFU and ADA among the four groups (F = 1.852, 0.958, 2.470, 1.423, 1.178,
      1.342, 0.611, P > 0.05). CONCLUSIONS: The level of ALP, CK, CKMB but the ALP
      level decreases distinctly after the garlicin and 5'NT increases evidently in
      BALF of PCP infected rats, but the ALP level decreases distinctly after the
      garlicin treatment.

PMID- 18038801
TI  - [Retrieving eco-environment factors relevant to Oncomelania snail distribution
      based on QuickBird image].
AB  - OBJECTIVE: To estimate snail distribution by using high spatial resolution
      QuickBird image on the basis of retrieving the eco-environment factors relevant
      to snail distribution. METHODS: Combined with the well-positioned ground data of
      Oncomelania snails, the meter-level high spatial resolution QuickBird image was
      used to retrieve the eco-environment factors related to snail distribution in
      Jiangxin village of Dangtu county, Anhui Province. The factors included
      vegetation (vegetation index and vegetation cover ratio) and soil (soil texture,
      soil cover type and humidity). A qualitative analysis was made by using principle
      component analysis, K-T transformation and supervision classification methods to
      retrieve the eco-environment factors. The vegetation index NDVI (Normalized
      Difference Vegetation Index) and MSAVI (Modified Soil Adjustment Vegetation
      Index) were calculated, and LAI (Leaf area index) and F (vegetation cover ratio)
      were retrieved. Information from QuickBird data and corresponding ground data
      were then used to analyze the relationship between snail distribution and
      environmental factors by using ArcGIS and statistical software. RESULTS: Snail
      data were received from 153 ground distribution spots and a GIS database on
      spacial distribution of snails was established. This database covered snail
      density, NDVI, MSAVI, LAI(NDVI), LAI(MSAVI), F(NDVI), F(MSAVI), PCA-1, PCA-2, PCA
      3, KT-1, KT-2 and KT-3. Statistical analysis showed that the snail density could
      be estimated by LAINDVI and FMSAVI quantitatively based on the following
      regression model: Y = -3.919 + 1.22 LAI(MSVI) + 16.076 F(MSAVI). Decision index
      of the regression model was 0.2. CONCLUSIONS: A quantitative regression model
      between Oncomelania snail distribution and environmental variables retrieved from
      QuickBird images has been established, which may have a wide application
      prospect. KT-1, KT-2 and KT-3. Statistical analysis showed that the snail density
      could be estimated by LAINDVI and FMSAVI quantitatively based on the following
      regression model: Y = -3.919 + 1.22 LAI(MSAVI) + 16.076 F(MSAVI). Decision index
      of the regression model was 0.2. CONCLUSIONS: A quantitative regression model
      between Oncomelania snail distribution and environmental variables retrieved from
      QuickBird images has been established, which may have a wide application
      prospect.

PMID- 18038802
TI  - [Investigation of mosquito abundance and composition around the Rare Birds
      National Nature Reserve of Yancheng, Jiangsu Province].
AB  - OBJECTIVE: To investigate the mosquito abundance and their relative species
      composition within and outside the Rare Birds National Nature Reserve of
      Yancheng, Jiangsu Province. METHODS: Sampling was carried out between May and
      Oct. 2004 at two weeks interval in two foci (the Reserve and nearby residential
      district) in Sheyang County. Mosquitoes were collected with the modified CDC
      light trap. Density was calculated, and species were identified. Environmental
      temperatures, rainfall and relative humidity were monitored during the study.
      RESULTS: A total of 40,912 mosquitoes were captured in the two foci. The sampled
      mosquitoes were identified as 4 species belonging to three genera (Anopheles
      sinensis, Culex pipiens pallens, Cx. tritaeniorhynchus, and Armigeres
      subalbatus). The most abundant mosquito species was An. sinensis and Cx pipiens
      pallens, which accounted for 97.7% of the whole number. 92% and 8% of the total
      amount of mosquitoes were collected from the nature reserve and residential
      district respectively. The most abundant species in the nature reserve and
      residential district was An. sinensis (60.6%) and Cx. pipiens pallens (76%),
      respectively. Within the nature reserve, there were two peaks occurred in adult
      abundance, in mid- and late July and mid-Sept. The abundance of mosquitoes in the
      area was positively correlated to the temperature (r = 0.765, P = 0.005).
      CONCLUSION: The wetland is an ideal breeding place for An. sinensis and Cx
      pipiens pallens. The peaks of mosquito abundance are in mid- and late July and
      mid-Sept. It is of importance to carry out surveillance on mosquito vectors with
      pathogen-transmitting potential.

PMID- 18038803
TI  - [Cloning and optimized prokaryotic expression of a pbmag-1 cDNA fragment from
      Plasmodium berghei ANKA].
AB  - OBJECTIVE: To clone and express a novel gene cDNA fragment, pbmag-1, from
      Plasmodium berghei ANKA strain. METHODS: The cDNA sequence of pbmag-1 was
      obtained from the GenBank of P. berghei ANKA genomic databases, with which a pair
      of primers was designed and RT-PCR was used to get a cDNA fragment of the gene
      from the parasite. The expanded cDNA 3' fragment of the gene was obtained by 3'
      RACE using the oligo dT primer and a set of specific primers. The intact cDNA 3'
      fragment was cloned into a prokaryotic expressional vector and transformed into
      the BL21-(DE3)-RIL strain of Escherichia coli. The recombinant protein of PbMAg-1
      was expressed with an optimized strategy and used to immunize mice. RESULTS: The
      pbmag-1 cDNA fragment obtained was 1341 bp in length, A/T rich (73%) and with a
      correct 3' end sequence. By Western blot, the anti-serum of mice immunized with
      the recombinant protein of PbMAg-1/GST, which was expressed as inclusion bodies,
      specifically recognized a band with Mr 64,000 molecule from the protein extracts
      of P. berghei-infected mouse erythrocytes. CONCLUSION: The pbmag-l cDNA sequence
      with intact 3' has been obtained, which will be used for further study on its
      role in the immune response of P. berghei infection.

PMID- 18038804
TI  - [Construction of the recombinant secretion type BCG-Eg95 vaccine of Echinococcus
      granulosus].
AB  - OBJECTIVE: To construct the recombinant secretion type BCG-Eg95 vaccine of
      Echinococcus granulosus (rsBCG-Eg95). METHODS: BCG-Ag85B signal sequence with 117
      bp and Eg95 gene with 471 bp were amplified from the genome of BCG and pGEX-4T
      Eg95 by PCR, respectively. BCG-Ag85B signal coding gene and Eg95 gene were cloned
      into E. coli-BCG shuttle-vector pMV261 to get the recombinant plasmid pSMEg95,
      which was confirmed by restriction endonuclease digestion, PCR amplification and
      gene sequencing. These recombinant plasmids were introduced into BCG by
      electroporation for the construction of rsBCG-Eg95 vaccine. The rsBCG-Eg95
      positive clones were screened by Kan+ and identified by PCR amplification.
      RESULTS: BCG-Ag85B signal sequence coding gene and Eg95 coding gene were
      successfully cloned into pMV261, which was confirmed by restriction endonuclease
      digestion, PCR amplification and sequencing of the plasmid pSMEg95. The plasmids
      were introduced into BCG and confirmed as the recombinant secreting BCG-Eg95
      vaccine of E. granulosus (rsBCG-Eg95). CONCLUSION: The recombinant secretion type
      BCG-Eg95 vaccine (rsBCG-Eg95) of E. granulosus with BCG-Ag85B signal sequence and
      Eg95 gene has been constructed.

PMID- 18038805
TI  - [Detection of mite allergens in the dust of filter-net and air of air-conditioned
      room].
AB  - OBJECTIVE: To detect mite allergens in the dust of air conditioner filter-net and
      floating air in room. METHODS: Samples were collected from rooms of asthma
      patient and normal families with or without air conditioner. Der p1, Der f1 and
      Der 2 were determined by two monoclonal antibody-based ELISA. RESULTS: In asthma
      patient families, the concentration of airborne Der p1, Der f1 and Der 2 was
      (0.23 +/- 0.13), (2.62 +/- 1.08), (0.93 +/- 0.41) ng/m3, and (0.56 +/- 0.25),
      (4.74 +/- 1.22), (2.33 +/- 0.64) ng/m3 respectively before and after the air
      conditioner switched on, all showing a significant difference (P < 0.05). In
      families without asthma patient, the concentration of Der p1, Der f1 and Der 2
      was (0.33 +/- 0.11), (11.50 +/- 3.08) and (2.10 +/- 0.80) ng/m3, and (0.63 +/-
      0.23), (19.80 +/- 4.30) and (3.60 +/- 1.00) ng/m3 respectively before and after
      the air conditioner switched on, also showing a significant difference (P <
      0.05). From the filter-net dust of air conditioner in family with allergic asthma
      patient, the concentration of Der p1, Der f1 and Der 2 was (0.52 +/- 0.19), (3.34
      +/- 0.63), (2.53 +/- 0.65) microg/g dust, while that of normal families was (1.30
      +/- 0.35), (5.16 +/- 0.92), (3.47 +/- 1.13) microg/g dust respectively. The
      concentration of Der f1 and Der 2 at both asthma families and normal families was
      higher than 2 microg/g, an allergen concentration threshold. CONCLUSION: Mite
      allergens exist in the filter-net dust of air conditioner, which may be an
      important source of indoor allergens and a cause of the increasing prevalence of
      allergic asthma.

PMID- 18038806
TI  - [Construction and expression of prokaryotic expression plasmids of Pneumocystis
      carinii p55 antigen gene fragment].
AB  - OBJECTIVE: To construct prokaryotic recombinant expression plasmid carrying
      Pneumocystis carinii Mr 55 000 antigen (p55) gene fragment and express the
      recombinant protein. METHODS: P. carinii pneumonia (PcP) rat models were
      established by subcutaneous injection of dexamethasone for 14 weeks. Total RNA
      was extracted from lung of P. carinii rat and p55 antigen gene fragment was
      cloned by RT-PCR, which was identified by sequencing. The 690 bp fragment was
      cloned to pGEX-4T-1, the recombinant plasmid was screened and identified by
      restriction analysis and PCR. The recombinant plasmid was finally induced with
      IPTG to express a new fusion protein, and the products were analyzed by SDS-PAGE
      and Western blot. RESULTS: A fragment of 690 bp was obtained by RT-PCR. The
      recombinant pGEX-4T-1/690 was constructed. SDS-PAGE revealed that the molecular
      weight of the recombinant protein was approximately Mr 62,000, the maximum amount
      of the fusion protein produced was 11.6% of the total protein. The recombinant
      protein can be recognized by GST antibody and by the sera from P. carinii
      infected rats using Western blotting. CONCLUSION: Prokaryotic expression plasmid
      pGEX-4T-1/690 has been constructed and the recombinant fusion protein shows
      antigenicity.

PMID- 18038807
TI  - [Clinical observation on 25 cases of severe angiostrongyliasis cantonensis].
AB  - OBJECTIVE: To summarize the clinical features of severe angiostrongyliasis
      cantonensis (AC) patients. METHODS: Clinical data on symptoms, physical signs,
      auxiliary examination and prognosis of 25 severe AC patients hospitalized in June
      Sept 2006 were analyzed. RESULTS: Epidemiologically, all cases had eaten uncooked
      fresh water snails. One of the early symptoms was fever (16 cases, 64.0%),
      including 8 cases with low-grade fever, 7 cases with mid-range fever, and 1 case
      high fever. Nervous system manifestation: (1) All cases had headache, entire
      headache (56.0%) or partial (44.0%), especially in occipitalis. (2) Patients had
      distinct degree neck rigidity, with negative pathologic reflex; 12 cases had
      nausea and vomiting (48.0%). (3) 20 cases (80.0%) had skin paresthesia, 5 had
      severe pain and hyperalgia on skin; 3 cases with skin numbness, and 2 with
      thermohypesthesia. (4) 11 cases (44.0%) appear distinct degree depraved vision; 3
      cases had photophobia, 5 with blur vision, 1 each with diplopia, defect of field
      vision or bug sign, respectively. (5) Nasolabial groove became shallow and
      distortion of commissure in 4 cases (16.0%), and 2 cases (8.0%) couldn't close up
      eyelid. (6) 4 cases had sustained or curative tinnitus. Laboratory examination
      showed that eosinophilic granulocytes increased in both peripheral blood and
      cerebrospinal fluid. Skull MRI for 14 cases revealed linear enhancement in local
      meninx or abnormal enhancement in cerebral parenchyma. Chest CT examination in 7
      cases showed nodule shadow and spot flaky ground-glass shadow in lungs. One and 3
      months after being discharged from hospital, 12 patients (48.0%) still had
      sequelaes--7 cases had tingling sensation on skin, 1 case had temperature
      sensation dysfunction on the skin of chest and abdomen, 3 cases had headache
      occasionally, and 1 case still had defect of field vision. CONCLUSION: Central
      nervous system has been impaired in the angiostrongyliasis cantonensis patients
      who may need a longer convalescent period.

PMID- 18038808
TI  - [Regulation mechanism of variation in Plasmodium falciparum var gene family].
AB  - This is a review on the new progress in the study of regulation mechanism of
      Plasmodium falciparum Var gene family. The mutually exclusive expression system
      caused expression only one in 60 var genes while others were silenced. It was
      regulated on the transcriptional level mainly through three pathways: non-coding
      DNA elements, chromatin structure and perinuclear localization.

PMID- 18038809
TI  - [Research and perspectives in parasitology].
AB  - This article reviews the recent achievements in parasitology including new
      diagnostic techniques, molecular mechanism of parasitic pathogenesis, drug
      resistance, antigenic variation, parasite genomics and proteomics. The
      perspective development in the area is also discussed.

PMID- 18038810
TI  - [Ultrasonic diagnosis of clonorchiasis sinensis].
AB  - This is to retrospectively review and summarize the ultrasonic images of 214
      patients who were diagnosed as clonorchiasis and received treatment. The major
      changes in ultrasonography were found in gallbladder and hepatic bile duct.
      Flocculent echos in the gallbladder were the characteristic feature, which
      disappeared after chemotherapy. The wall of hepatic bile duct became thicker and
      shaggy in most patients. These changes improved quite slowly after treatment.
      Ultrasonography is of value in the diagnosis of clonorchiasis sinensis

PMID- 18038811
TI  - [Epidemiological survey on Echinococcus infection in animals in Qinghai
      Province].
AB  - Parasitological and dissection methods were used to confirm Echinococcus
      infection and echinococcosis in animals, and to understand the epidemiological
      situation in final and intermediate animal hosts in Qinghai Province. Three
      Echinococcus species were found in the Province including E. granulosus, E.
      multilocularis and E. shiquicus. The prevalence of hydatid disease showed a
      tendency of increase with an average rate of over 50% in yaks and sheep. Higher
      prevalence in wild animals as intermediate host was found in the southern
      plateau, while that in final hosts such as dogs and wolves, the prevalence was
      higher in the area of Qilian mountain. There is a complex chain of life cycle of
      the parasites among animals, which poses a threat to the health of human
      population. Effective measures to control the disease in animals are urgently
      needed.

PMID- 18038812
TI  - [Cloning and construction of nucleic acid vaccine of FABP gene cDNA from
      Echinococcus granulosus].
AB  - Specific primers were designed according to published nucleotide sequence of FABP
      (fatty acid binding protein) gene in the GenBank database. The kozak sequence
      (CCACC) was introduced at the upstream of initiator. The total RNA was extracted
      from protoscoleces of Echinococcus granulosus (Inner Mongol isolate). The FABP
      gene cDNA fragment was amplified by RT-PCR and cloned into pMD19-T vector for
      sequencing and analyzing. The cloned FABP gene cDNA was with 402bp. The ORF
      encoded 133 amino acids. The amplified cDNA fragment was subcloned into pCDNA3.1
      (+) vector. The results showed that the nucleic acid vaccine candidate pcDNA-FABP
      NM has been constructed.

PMID- 18038813
TI  - [Determination of trace elements in hair of mice infected with Trichinella
      spiralis].
AB  - Mice were divided into 3 groups: heavy infection group with 80 mice each was fed
      with 400 muscle larvae of Trichinella spiralis, light infection group with 60
      mice each was fed by 200 larvae, and uninfected control (60 mice) . The content
      of Cu, Zn and Fe in the dorsal hair samples was measured in the week of 1, 3, 5,
      7, 9, 11, 13 and 15 after infection. Results indicated that the content of Zn, Cu
      and Fe in the two experimental groups reduced considerably in comparison to the
      control (P < 0.05), especially for that of Zn and Cu. Lower content was found in
      the heavily infected mice than in those with light infection (P < 0.05).

PMID- 18038814
TI  - [Solid medium-filter paper cultivation of Ancylostoma caninum larvae].
AB  - Consisted of beef extract (3 grams), peptone (10 grams), sodium chloride (5
      grams), agar (20 grams) and distilled water, the solid medium was used with
      filter paper for cultivation of the larvae of Ancylostoma caninum. The method
      shows higher detection rate and simpler operation than the traditional test tube
      filter paper culture technique.

PMID- 18038815
TI  - Safe patient handling and movement: time for a culture change.

PMID- 18038816
TI  - Surviving shift work.

PMID- 18038817
TI  - Nurses set to make decisions on CPR.

PMID- 18038818
TI  - The NHS is treating its job applicants with disrespect.

PMID- 18038819
TI  - People tell me they pay their taxes and so can specify the treatment they want.

PMID- 18038820
TI  - Bringing stroke out of the shadows.

PMID- 18038821
TI  - Pulling together in general practice.

PMID- 18038822
TI  - HPV vaccination of girls to help prevent cervical cancer.

PMID- 18038823
TI  - Bowel care. Part 4--Administering an enema.

PMID- 18038824
TI  - Understanding Meniere's disease 1: causes and diagnosis.
AB  - This is part 1 of a two-part unit on Meniere's disease and tinnitus. It examines
      the definition and symptoms of Meniere's, its causes, incidence and risk factors.
      It identifies the difficulties faced by patients, as well as the problems
      healthcare professionals have in making this diagnosis.

PMID- 18038825
TI  - Emergency oxygen for respiratory patients.
AB  - Oxygen is prescribed for hypoxaemic patients to increase alveolar oxygen tension
      and decrease the effort of breathing. Although principally life saving, in
      certain circumstances it can be lethal if prescribed and/or administered
      incorrectly. To ensure safe, effective delivery of oxygen, health professionals
      dealing with the administration, titration and monitoring of oxygen therapy
      should understand the principles that underpin its use. Carol Kelly and Anne
      Riches discuss administering oxygen therapy in the acute situation.

PMID- 18038826
TI  - Understanding why we use spirometry: part one.
AB  - Rachel Booker discusses why spirometry is used and the interpretation of results.
      In part two she describes the procedure for using spirometry.

PMID- 18038827
TI  - Carrying out accurate spirometry testing: part 2.
AB  - Rachel Booker describes the procedure for using spirometry.

PMID- 18038828
TI  - The role of asthma link nurses for schools.
AB  - Debra Forster and Claire Winser discuss how collaborative working in an asthma
      service has improved the care of children with asthma in Nottingham.

PMID- 18038829
TI  - Get connected.

PMID- 18038830
TI  - The importance of good teamwork.

PMID- 18038831
TI  - Making an impact. Interview by Ruth Williams.

PMID- 18038832
TI  - Developing hardiness in nurse managers.

PMID- 18038833
TI  - Cleaning up sterile services.

PMID- 18038834
TI  - Ten steps to writing curricula vitae.

PMID- 18038835
TI  - Using systematic reviews.

PMID- 18038836
TI  - Will next year's pay award help nurses to catch up with other workers?

PMID- 18038837
TI  - Libyan jail ordeal.
AB  - In July this year, five Bulgarian nurses and a trainee doctor were finally
      released from a Libyan prison where they had been held for eight years. All were
      accused of deliberately infecting more than 400 children with HIV.

PMID- 18038838
TI  - Body and soul.
AB  - The rewards from nursing and the ministry are not dissimilar. It is argued that
      it is impossible to minister to the body without ministering to the soul.

PMID- 18038839
TI  - The forgotten disease.
AB  - Polio still affects the lives of the survivors, causing problems if they need
      investigations or hospital treatment.

PMID- 18038840
TI  - NHS not as 'Sicko' as we thought.

PMID- 18038841
TI  - Employment experiences of older nurses and midwives in the NHS.
AB  - AIM: To examine the employment experiences of older nurses and midwives working
      in the NHS. METHOD: A total of 27 semi-structured telephone interviews were
      conducted with nurses and midwives to identify positive and negative aspects of
      their working lives in the NHS. The interviewees were selected from a potential
      pool of 87 nurses and midwives who had consented to be involved in an earlier
      part of the study. Data were analysed using QSR NVivo 7.0. FINDINGS: Positive and
      negative issues were identified as having an impact on the quality of working
      life. These included: access to training, change and Agenda for Change (AfC),
      quality of management, work demands, patient/colleague contact and nursing and
      midwifery as a career. CONCLUSION: This study highlighted a number of issues
      relevant to older nurses and midwives that warrant further study and attention.
      These include access to training and continuing professional development, issues
      relating to change and AfC, and general work demands including workload,
      resources and morale. The ability of staff to remain healthy, committed and able
      to deliver quality care can be compromised in cases where the staff experience is
      negative.

PMID- 18038842
TI  - Providing pain relief for patients in the emergency department.
AB  - This article examines literature on pain relief in the emergency department (ED).
      The term 'emergency department' has been substituted for 'accident and emergency'
      for the purposes of international continuity. Much of the available research
      paints a negative picture of pain assessment and management in this setting.
      However, there is evidence of positive developments in clinical practice that
      have the potential to improve the patient's experience in the ED.

PMID- 18038843
TI  - Wound closure using adhesive strips.
AB  - This article outlines the use of adhesive strips which may be suitable for
      closing many superficial wounds, pre-tibial lacerations and surgical wounds
      requiring support.

PMID- 18038844
TI  - An overview of antibiotic therapy.
AB  - Antibiotics are one of the most widely prescribed group of drugs in the UK.
      However, their widespread use has resulted in antibiotic resistance and
      unnecessary prescribing. This article provides an overview of antibiotic therapy,
      including the principles and modes of action of drug treatment, prescribing
      criteria and the issue of antibiotic resistance.

PMID- 18038845
TI  - Epidural analgesia.

PMID- 18038846
TI  - No students for me.

PMID- 18038847
TI  - Happy to stay in Lebanon.

PMID- 18038848
TI  - Know yourself, know your patients.

PMID- 18038849
TI  - Scope of practice issues: dental hygienists and dental assistants.

PMID- 18038850
TI  - Overview of the Frew settlement and new fee increases.

PMID- 18038851
TI  - We need you to become a Medicaid provider.

PMID- 18038853
TI  - Texas State Board of Dental Examiners: legislation.

PMID- 18038852
TI  - The First Dental Home Project: an opportunity for Texas to improve access to
      dental care.

PMID- 18038854
TI  - The changing face of the Texas State Board of Dental Examiners.

PMID- 18038855
TI  - State taxes: legislature fine-tunes revised franchise tax; allocates additional
      funding for future property tax cuts.

PMID- 18038856
TI  - TDA 2009: continuing the focus on advocacy.

PMID- 18038857
TI  - Meet the consultants to the Council on Legislative and Regulatory Affairs.

PMID- 18038858
TI  - Intra-operative digital photography with the dental operating microscope.

PMID- 18038859
TI  - Long-term care expenses: plan for them.

PMID- 18038860
TI  - Oral and maxillofacial pathology case of the month. Myofibroma.

PMID- 18038861
TI  - Education policy is health policy.

PMID- 18038862
TI  - The future of property tax exemption for nonprofit health care organizations.

PMID- 18038863
TI  - How much is enough? An evidence-based framework for setting Medicaid payment
      rates.
AB  - This article proposes an evidence-based framework for Medicaid programs to use in
      setting payment levels for any health care service. The purpose of payment is
      seen from the beneficiary's perspective, that is, enabling access to quality
      services. The approach is to measure access as directly as possible, to make
      findings about payment adequacy, and to take action in a way that maximizes the
      return (i.e., access to quality care) on Medicaid's investment. This approach
      differs from both the theoretical ideal and from much of the past practice in
      Medicaid rate setting. The paper offers examples of evidence, findings, and
      actions.

PMID- 18038864
TI  - Why do Hispanics have so little employer-sponsored health insurance?
AB  - This paper investigates low rates of employer health insurance coverage among
      Hispanics using national data from the Community Tracking Study Household Survey.
      Interview language served as a proxy for the degree of assimilation. Findings
      indicate that English-speaking Hispanics are more similar to whites in their
      labor market experiences and coverage than they are to Spanish-speaking
      Hispanics. Spanish-speakers' very low human capital (including their inability to
      speak English) results in much less access to job-based insurance. Though less
      important, Spanish-speaking Hispanics' demand for employer-sponsored insurance
      appears lower than that of English-speaking Hispanics or whites. Results suggest
      that language and job training may be the most effective way to bolster
      Hispanics' insurance coverage.

PMID- 18038865
TI  - The relative importance of worker, firm, and market characteristics for
      racial/ethnic disparities in employer-sponsored health Insurance.
AB  - The characteristics of an individual, the local labor market, and the firm where
      an individual is employed each may be associated with racial and ethnic
      disparities in employer-sponsored insurance (ESI). This study estimates two
      models to determine the relative effects of each of these three sets of
      characteristics on the likelihood a worker has a job with ESI. One model has two
      outcomes: the job comes with ESI or not. The other model has five possible
      outcomes: the individual is not offered ESI and is uninsured, the individual is
      not offered ESI and is insured; the individual is offered ESI but turns it down
      and is uninsured; the individual is offered ESI but turns it down and is insured;
      and the individual is offered ESI and accepts. Findings indicate that individual
      characteristics and firm characteristics are more likely to have significant and
      substantial effects on the probability that a person has ESI, while the effects
      of market characteristics appear to be conveyed through firm characteristics.
      Being African American or Hispanic is not significantly associated with having
      ESI in the two-outcomes model, but in the five-outcomes model each is associated
      significantly with being uninsured, either because the person has not been
      offered ESI or has declined offered coverage. Clearly, examining more nuanced
      outcomes is more informative about the role of race and ethnicity in why working
      people are uninsured.

PMID- 18038866
TI  - Individual health insurance within the family: can subsidies promote family
      coverage?
AB  - This paper examines the role of price in health insurance coverage decisions
      within the family to guide policy in promoting whole family coverage. We analyze
      the factors that affect individual health insurance coverage among families, and
      explore family decisions about whom to cover and whom to leave uninsured. The
      analysis uses household data from California combined with abstracted individual
      health plan benefit and premium data. We find that premium subsidies for
      individual insurance would increase family coverage; however, their effect likely
      would be small relative to their implementation cost.

PMID- 18038867
TI  - Effects of specialty hospitals on the financial performance of general hospitals,
      1997-2004.
AB  - Hospital specialization has become a controversial topic, culminating in a
      moratorium issued in 2003 by Congress directing the Centers for Medicare and
      Medicaid Services to cease payments to new physician-owned specialty hospitals
      for those Medicare and Medicaid patients referred by physicians with a financial
      interest in the facility. This paper focuses on one important economic question:
      does the presence of specialty hospitals in a market affect general hospitals'
      financial performance? We estimate longitudinal fixed-effects models for a
      national panel of short-term acute care hospitals for the period 1997 though
      2004; models are estimated for general hospital patient-care revenue, costs, and
      operating margins. We find that the presence of one or more new or established
      specialty hospitals in a market has a negative effect on general hospital costs
      and a positive effect on general hospital operating margins. Results, which were
      consistent across several different modeling approaches, imply that the presence
      of specialty hospitals encourages greater efficiency on the part of incumbent
      general hospitals, and the existence of profits attracts market entry. Our
      findings question the contention that competition from specialty hospitals harms
      general hospitals financially.

PMID- 18038868
TI  - Hospital inefficiency: what is the impact of membership in different types of
      systems?
AB  - The primary objective of this study is to assess whether systematic differences
      in inefficiency are associated with hospital membership in different types of
      systems. We employed the Battese/Coelli simultaneous stochastic frontier analysis
      (SFA) technique to estimate hospital cost inefficiency. Mean estimated
      inefficiency was 8.42%. Membership in different types of systems was related to
      estimated cost inefficiency (p < .05). Compared to hospitals that were members of
      centralized health systems, membership in centralized physician/insurance or
      decentralized systems was associated with decreased inefficiency; membership in
      independent systems was associated with increased inefficiency.

PMID- 18038869
TI  - Genetic discrimination in health insurance: current legal protections and
      industry practices.
AB  - Most states have enacted genetic nondiscrimination laws in health insurance, and
      federal legislation is pending in Congress. Scientists worry fear of
      discrimination discourages some patients from participating in clinical trials
      and hampers important medical research. This paper describes a study of medical
      underwriting practices in the individual health insurance market related to
      genetic information. Underwriters from 23 companies participated in a survey that
      asked them to underwrite four pairs of hypothetical applicants for health
      insurance. One person in each pair had received a positive genetic test result
      indicating increased risk of a future health condition--breast cancer,
      hemochromatosis, or heart disease--for a total of 92 underwriting decisions on
      applications involving genetic information. In seven of these 92 applications,
      underwriters said they would deny coverage, place a surcharge on premiums,or
      limit covered benefits based on an applicant's genetic information.

PMID- 18038870
TI  - Long-term results of a phase-I/II study of sequential high-dose chemotherapy with
      autologous stem cell transplantation in the initial treatment of aggressive non
      Hodgkin's lymphoma.
AB  - AIMS AND BACKGROUND: To improve the survival of patients with aggressive non
      Hodgkin's lymphoma, we evaluated a risk-adapted therapeutic approach using high
      dose (HD) or conventional-dose (CD) chemotherapy (CT) for poor-risk and good-risk
      patients, respectively. METHODS: Twenty patients were treated in each group. In
      both groups, the first chemotherapy cycle consisted of dexamethasone,
      vincristine, ifosfamide, and etoposide. Thereafter, the CD or HD patients
      received 3 or 2 cycles of dexamethasone, vincristine, epirubicin, and
      cyclophosphamide, respectively, followed by 1 cycle of dexamethasone,
      carboplatin, and etoposide. In the HD group cyclophosphamide, epirubicin,
      carboplatin, and etoposide were dose-escalated by a factor of 6, 3, 3, and 3,
      respectively, as compared to the CD group, and autologous peripheral blood stem
      cells were administered after each HD-CT cycle. RESULTS: Grade III-IV toxicities
      were neutropenia and thrombocytopenia (100%), anemia (55%), and stomatitis (30%)
      in patients with HD-CT, and neutropenia (90%) in patients with CD-CT. One toxic
      death occurred in a patient with HD-CT. The overall response rate was 100% in HD
      CT patients, including 70% complete remissions, and 80% in CD-CT patients,
      including 60% complete remissions. The 10-year overall survival was 55% for
      patients with HD-CT and 80% for patients with CD-CT. CONCLUSIONS: The risk
      adapted treatment approach showed tolerable toxicities and was associated with
      encouraging results.

PMID- 18038871
TI  - Cancer chemotherapy near the end of life: the time has come to set guidelines for
      its appropriate use.
AB  - AIMS AND BACKGROUND: This study retrospectively analyzes the use of chemotherapy
      in patients who died of advanced cancer either after having been in care at the
      Medical Oncology Unit (MOU) of the University Hospital of Bologna, Italy, or
      after having been assisted in their terminal disease phase by the Bologna
      Oncological Hospice at Home (OHH) of the Associazione Nazionale Tumori (ANT)
      Italia Foundation. In the latter group, the prescription and delivery of
      chemotherapy had been performed by doctors of medical oncology departments other
      than the MOU. RESULTS: Between January 2003 and September 2005, 793 deaths of
      patients were recorded (MOU: 312; OHH: 481). At least one cycle of chemotherapy
      had been received by 445 patients (56.1%). The most common cancer types were lung
      cancer (26.7%), colorectal cancer (14.8%), and breast cancer (11.2%). At the time
      of the last chemotherapy (I-CT), the median age of the patients was 68 years
      (range, 22-98 years) and the median KPS was 70 (range, 40-100). The median
      interval between I-CT and death was 71 days (range, 1-1913 days). One hundred and
      one patients (22.7%) had received their I-CT in the last 30 days of their life,
      86% of them having intermediately chemosensitive (71%) or chemoresistant (14%)
      tumors. The I-CT in the last month of life was first line in 56% of cases and
      consisted of costly new-generation drugs in 36.6% of cases. CONCLUSIONS: The
      study suggests the urgent need to lay down guidelines for the appropriate use of
      chemotherapy in advanced cancer patients with a short life expectancy.

PMID- 18038872
TI  - Mesenchymal chondrosarcoma. An analysis of patients treated at a single
      institution.
AB  - BACKGROUND: We analyzed clinical and treatment-related factors influencing the
      outcome of patients with mesenchymal chondrosarcoma (MC). Twenty-six patients
      (median age, 31 years) were identified using the Tumor Center and Chemotherapy
      Department database of the study institute. METHODS: Patients received surgery
      (24 patients) and/or radiotherapy (5 patients), and chemotherapy (12 patients).
      RESULTS: After a median follow-up of 48 months (7-237 months) 10 patients were
      alive. The 10-year overall survival (OS) was 27% in those who achieved complete
      surgical remission and 0% in those who did not (P = 0.0007). A worse 10-year
      probability of OS was observed in patients who were metastatic at presentation
      (metastatic 0%, localized 31%, P = 0.02), in patients with soft tissue MC (soft
      tissue MC 0%, bone MC 29%, P = 0.06) and in hemangiopericytoma-like MC
      (hemangiopericytoma-like MC 0%, Ewing's-like MC 33.5%, P = 0.9). In those
      patients who achieved complete surgical remission, the 10-year DFS was 76% for
      those who received chemotherapy and 17% for those who did not (P = 0.008).
      CONCLUSIONS: Our experience confirmed the importance of complete surgical
      remission in MC treatment and suggests that the addition of chemotherapy should
      offer a benefit in terms of DFS. Due to the rarity of MC, multicentrer studies
      are needed to identify the most active chemotherapy regimen.

PMID- 18038873
TI  - Late relapse in testicular germ cell tumors.
AB  - AIMS AND BACKGROUND: Analysis of patients with late relapse of testicular germ
      cell tumors (GCTs) with reports on clinicopathological features and outcomes.
      METHODS: We identified all patients diagnosed with testicular GCTs at our
      Institute between 1988 and 2004 who developed relapse > or = 24 months after
      completion of primary therapy. A retrospective case-note review was performed to
      extract clinical, pathological, treatment and outcome data. RESULTS: Six patients
      (1.25%) developed late relapse. All patients presented with stage I disease and
      were classified as "good risk" according to the International Germ Cell Consensus
      Classification. Mean time to late relapse was 48 months. Markers at late relapse
      were normal in all patients. Relapse was confined to retroperitoneal sites in
      five patients and located in the mediastinum in one patient. Five patients were
      managed by chemotherapy alone while one underwent combined treatment with surgery
      followed by chemotherapy. All patients obtained a complete response and all
      remained free from recurrence with a mean follow-up of 115 months. CONCLUSIONS:
      The incidence of late relapse in this small series is low. Chemonaive patients
      with late relapse were successfully salvaged with chemotherapy alone or surgical
      excision followed by cisplatin-based chemotherapy. The optimal duration of follow
      up in patients with testicular GCTs is not known and practice varies widely. At
      our Institute we advise lifelong follow-up of all patients with malignant GCTs of
      the testis.

PMID- 18038874
TI  - The variability of applicator position among high dose rate intracavitary
      brachytherapy applications in cervical cancer patients treated with ring & tandem
      applicators.
AB  - OBJECTIVE: To evaluate the interindividual and intraindividual applicator
      position variability in high dose rate ring and tandem intracavitary
      brachytherapy applications in locally advanced cervical cancer. PATIENTS AND
      METHODS: Eight patients with locally advanced cervical cancer formed the study
      population. They had been treated in Dokuz Eylul University Department of
      Radiation Oncology between the years 2000 and 2005 with high dose rate
      intracavitary brachytherapy using ring and tandem applicators. The 3-dimensional
      geometric variation of the applicator center in craniocaudal, mediolateral and
      anteroposterior directions was determined on the basis of bony reference points
      in 24 pairs of orthogonal films obtained in the conventional simulator. Then the
      following evaluations were performed: 1) the applicator position variability in
      all applications (interindividual variability), 2) the intraindividual applicator
      position variability relative to the first application, 3) the intraindividual
      applicator position variability relative to the average of three applications.
      Among the potential factors that might influence the reproducibility of ring and
      tandem applications, age, stage, the period between external radiotherapy and
      brachytherapy were evaluated by univariate analysis. RESULTS: Standard deviation
      of interindividual applicator variability was 3.83 mm in craniocaudal, 0.39 mm in
      mediolateral and 2.86 mm in anteroposterior directions. The standard deviation of
      intraindividual variability relative to the first application was 1.91 mm in
      craniocaudal, 0.4 mm in mediolateral, and 4.26 mm in anteroposterior directions.
      The standard deviation of intraindividual variability relative to the average of
      three applications was 0.95 mm in craniocaudal, 1.86 mm in mediolateral, and 1.24
      mm in anteroposterior directions. According to univariate analysis, no factor
      influenced applicator position variability. CONCLUSIONS: In order to extract
      definitive conclusions about factors that affect positional reproducibility of
      ring and tandem applicators, studies are needed that include larger numbers of
      patients.

PMID- 18038875
TI  - Patterns of care for brachytherapy in Europe, in Spain and Italy: comparative
      results.
AB  - AIMS AND BACKGROUND: The aim of the study was to compare the facilities for
      brachytherapy in two similar countries, as are Italy and Spain. This survey
      reports the differences in the use of brachytherapy in these countries. METHODS:
      The data regarding brachytherapy was obtained in 2002 by means of a specially
      designed web site, because Internet allowed the access to the questionnaire in an
      easy and safe way. In the first edition of the survey, only the countries in
      which more than 50% of its centers had completed the questionnaire were included.
      Among these countries there were Italy and Spain. RESULTS: Data was available in
      127 centers in Italy and 72 centers in Spain, where 35 and 39, respectively,
      provided brachytherapy. Although both countries had a similar number of
      radiotherapy patients and the average number of radiotherapy patients per center
      was similar in both countries (P = 0.29), there were several differences related
      to brachytherapy. For instance, the mean number of radiation oncologists
      regularly performing brachytherapy per center was higher in Spain (P = 0.001).
      There were also differences in the average number of patients per center in the
      following tumor sites: breast (P < 0.001) and gynaecological (P < 0.001). In
      fact, the average number of patients per center who were treated with
      brachytherapy in these tumor sites was higher in Spain than Italy. CONCLUSIONS:
      Although the estimated workload of the radiation oncologists, physicists and
      radiation technologists was higher in Spain, no statistically significant
      differences were found in the average number of patients per center for the
      following tumor sites: bronchus, head and neck, intracoronary, esophagus,
      prostate, rectum and skin. Several differences in the use of the brachytherapy
      procedures applied were also found.

PMID- 18038876
TI  - Benefit on biochemical control of adjuvant radiation therapy in patients with
      pathologically involved seminal vesicles after radical prostatectomy.
AB  - AIMS AND BACKGROUND: To determine whether there is a benefit for biochemical
      control with adjuvant radiation therapy to the surgical bed following radical
      prostatectomy in patients with seminal vesicle invasion and pathologically
      negative pelvic lymph nodes (pT3b-pT4 pN0). METHODS: We retrospectively reviewed
      the clinical records of radical prostatectomy patients treated between 1995 and
      2002. A total of 66 patients with seminal vesicle invasion were identified: 45 of
      these patients received adjuvant radiation therapy and 21 were observed.
      Radiation therapy was initiated within 4 months of prostatectomy. Median dose was
      66 Gy (range, 60-70 Gy). Median follow-up from the day of surgery was 40.6 months
      (mean, 41.5; range, 12-99). Biochemical recurrence was defined as the first value
      > or = 0.2 ng/ml. RESULTS: At two years, the proportion of patients free from
      biochemical recurrence was 80% in patients who received adjuvant radiation
      therapy versus 54% for those not given radiation therapy (P = 0.036). Actuarial
      biochemical recurrence at 5 years was 59% vs 41% for the radiation therapy and no
      radiation therapy groups, respectively. On univariate Cox regression model, the
      hazard of biochemical failure was also associated with a detectable (> or = 0.2
      ng/ml) postsurgical prostate-specific antigen (P = 0.02) prior to radiation
      therapy. Pathological T stage (pT3b vs pT4), Gleason score, primary Gleason
      pattern and positive surgical margins were not significantly associated with
      biochemical recurrence. The hazard of biochemical failure was around 85% lower in
      the radiation therapy group than in the observation group (P = 0.002).
      CONCLUSIONS: Data from the present series suggest that adjuvant radiation therapy
      for patients with seminal vesicle invasion and undetectable (< or = 0.2 ng/ml)
      postoperative prostate-specific antigen significantly reduces the likelihood of
      biochemical failure.

PMID- 18038877
TI  - Breast cancer diagnostic methods: screen-detected and clinical cases. An Italian
      survey of women's experiences.
AB  - AIMS AND BACKGROUND: The real practice of breast cancer diagnosis and treatment
      is often very different from guideline recommendations. Screening programs should
      minimize deviations from "best practice". The aim of the study was to compare
      cases detected by screening programs with cases that were not part of the public
      screening program, analyzing the diagnostic pathways from the first suspected
      breast problem to therapeutic intervention for breast cancer. METHODS: We
      interviewed a random sample of 268 women aged 49-70 years in three Italian
      regions (Lazio, Tuscany, Basilicata) who were treated for breast cancer,
      stratified by screening participation. RESULTS: In the nonscreened group, 48% of
      women were symptomatic and 50% were diagnosed by preventive tests. The proportion
      of women treated within 30 days of diagnosis was significantly lower in the
      screened group, 21.3% vs 35.8% (P = 0.0003). The mean number of tests
      (mammography, ultrasonography, cytology and histology) performed in the screened
      group was significantly higher than in the nonscreened group, 3.7 vs 2.8 (P =
      0.001). The percentage of women treated without a preoperative histological or
      cytological diagnosis was lower in the screened group than in the nonscreened
      group, 14% vs 25% (P = 0.024). CONCLUSION: Participation in screening programs
      seems to lead to more appropriate disease management even for breast cancer cases
      treated at the same hospital.

PMID- 18038878
TI  - Tumor vs non-tumor origin of occult and obscure gastrointestinal bleeding
      requiring hospitalization.
AB  - AIMS AND BACKGROUND: Occult/obscure gastrointestinal bleeding is often
      problematic to diagnose. It often leads to delayed treatment, a particularly
      dangerous circumstance when tumor origins are involved. This study reports the
      six-year experience of an Italian Surgery Center in the identification of the
      nature (tumor versus non tumor) and site of origin (upper, middle, lower
      gastrointestinal tract) of occult/obscure bleeding requiring hospitalization, as
      well as in its treatment. METHODS: Diagnostic instrumental examinations employed
      were: esophagogastroduodenoscopy, rectocolonoscopy, computerized tomography small
      bowel follow-through examination, capsule endoscopy, biopsy, angiography,
      abdominal computerized tomography scans and ultrasound. Therapies included:
      interventional radiology and surgery. RESULTS: Thirty-five cases of obscure and
      27 cases of occult bleeding were examined; all received a definite diagnosis
      during hospitalization. In the cases with obscure bleeding the diagnosis was
      inflammatory bowel disease (n = 7), angiodysplasia (5 gastric, 2 duodenal, 2
      jejunal, 3 ileal, 4 right colon), small bowel tumors (4 non-Hodgkin lymphomas, 1
      leiomyoma, 6 adenocarcinomas), and gastric metaplasia of Meckel's diverticulum (n
      = 1). There were significantly more nontumor lesions than tumors (P < 0.005), and
      a middle tract source was significantly more frequent than upper/lower tract
      sources (P < 0.0001). Intestinal resections were performed for all small bowel
      tumors (8 laparotomic, 3 laparoscopic), 5 angiodysplasias, all cases of
      inflammatory bowel disease and gastric metaplasia of Meckel's diverticulum;
      arterial embolization was performed for 11 angiodysplasias. In the cases with
      occult bleeding the diagnosis was sigmoid colon polyps in 6 (treatment,
      endoscopic polypectomy) and right colon cancer in 21 (treatment, right
      hemicolectomy). There were significantly more tumors than nontumor lesions (P <
      0.0001); all derived from the lower gastrointestinal tract. In all cases, the
      interventions resolved the bleeding completely. CONCLUSIONS: The results show
      that more than 50% of cases with obscure/occult bleeding requiring
      hospitalization are motivated by malignant gastrointestinal tumors, 34% of which
      are located in the small bowel, usually a difficult tract to explore. Thanks to
      modern technology, however, their diagnosis and treatment can nowadays be
      promptly and successfully achieved.

PMID- 18038879
TI  - Her2/neu expression by reverse transcriptase-polymerase chain reaction in the
      peripheral blood of prostate cancer patients.
AB  - BACKGROUND/AIMS: Evaluation of Her2/neu expression in the peripheral blood
      mononuclear cell fraction of prostate cancer patients by RT-PCR may afford an
      opportunity for the detection of circulating tumor cells and thus serve as a
      marker of micrometastatic disease. METHODS: We studied Her2/neu expression by
      reverse transcriptase-polymerase chain reaction in peripheral blood mononuclear
      cell fraction samples of 21 controls and serially in 43 patients with prostate
      cancer. RESULTS: None of the 21 controls expressed Her2/neu whereas 23.25% (95%
      CI, 11.75-38.63) of the patients were positive at entry into the study, and
      65.11% (95% CI, 49.07-78.99) of them had at least one positive result during the
      follow-up period. Her2/neu positivity at study entry did not correlate
      significantly with PSA level, Gleason score, clinical stage or time to PSA
      progression. When we analyzed only patients with advanced disease, we observed a
      trend towards a shorter time to PSA progression in patients with at least one
      positive Her2/neu result during the follow-up (log-rank test, P = 0.08).
      CONCLUSIONS: We conclude that Her2/neu expression in the peripheral blood
      mononuclear cell fraction of prostate cancer patients is frequent and therefore
      this assay may potentially be useful to detect the presence of micrometastatic
      disease in men with prostate cancer and for monitoring patients enrolled in
      trastuzumab-based therapeutic protocols.

PMID- 18038880
TI  - Low frequency of p53 and k-ras codon 12 mutations in non-small cell lung
      carcinoma (NSCLC) tumors and surgical margins.
AB  - AIMS AND BACKGROUND: Lung cancer is one of the most common cancers and has became
      a predominant cause of cancer-related death throughout the world. The k-ras codon
      12 mutation, which is the most common lung cancer mutation, is found in 15 to 30%
      of all lung cancers. Furthermore, the p53 gene has a very important role in the
      biological properties of tumor cells, and it is mutated in about 50% of non-small
      cell lung cancers. Residual tumor cells remain in surgical margins diagnosed as
      tumor free by histopathological techniques, and they can play a role in forming
      any local recurrence. Molecular methods may be exploited that are sensitive
      enough to detect small numbers of tumor cells. METHODS: In the present study, we
      examined p53 gene mutations and k-ras codon 12 mutations from the tumor samples
      and surgical margins of 34 non-small-cell lung cancer patients. P53 gene
      mutations were analyzed by single strand conformational polymorphism analysis,
      heterodublex analysis and DNA sequencing. K-ras codon 12 mutations were analyzed
      by the mutagenic PCR-restricted fragment length polymorphism method. RESULTS: A
      p53 mutation was detected only in primary tumors of 3 out of 34 patients (8.82%).
      These mutations were clustered in exon 5. Moreover, a k-ras codon 12 mutation was
      detected in both the primary tumor and the surgical margin tissues of 2 out of 34
      patients (5.88%). CONCLUSIONS: The detected mutation rate was low, in the range
      given in the literature. We think that different mechanisms related to other
      genes and individual genetic differences might play a role in cancer formation in
      our study group. We believe that molecular studies are necessary to identify
      biomarkers and to determine genetic alterations in histopathologically normal
      surgical margins.

PMID- 18038881
TI  - Curative surgery for gastric cancer in the elderly: treatment decisions, surgical
      morbidity, mortality, prognosis and quality of life.
AB  - AIMS AND BACKGROUND: Surgical risk is deemed to be higher in the aged population
      because there are often comorbidities that may affect the postoperative result.
      This consideration is important for the treatment decision-making for gastric
      cancer in the elderly. The aim of this study was to identify factors influencing
      mortality, morbidity, survival and quality of life after curative surgery for
      gastric cancer in patients aged 75 years and older, and to plan their appropriate
      management. METHODS AND STUDY DESIGN: From January 1993 to December 2004, 135
      patients underwent surgery at our department because of gastric cancer. Ninety
      four of these patients (69.6%) underwent potentially curative gastrectomy. A
      cross-sectional study of 23 patients aged 75 years and older and 71 younger
      patients who underwent curative gastrectomy was carried out: patient
      characteristics, tumor characteristics, management, morbidity, mortality,
      survival, and quality of life were evaluated. RESULTS: Elderly patients had
      significantly more comorbidities and a poorer nutritional status than younger
      patients. The surgical procedures were similar in both groups and the overall
      morbidity rate was 27.9% and the overall mortality rate 8.5%. Medical mortality
      was significantly higher in elderly patients, and the presence of comorbidities
      was the only independent factor affecting mortality. The 5-year survival rate was
      56.2% in the older group versus 62.1% in the younger group and tumor stage was
      the only prognostic factor influencing survival. Quality of life after surgery
      was similar in both groups. The significantly better postoperative functional
      outcome after subtotal gastrectomy suggested a better compliance of elderly
      patients with subtotal than total gastrectomy. CONCLUSIONS: In the elderly,
      surgical strategies must be modulated on the basis of comorbidities, tumor stage
      and future quality of life. Since elderly patients have no worse prognosis than
      younger patients, age is not a contraindication to curative resection for gastric
      cancer. Subtotal gastrectomy should be the procedure of choice mainly in elderly
      patients as it offers better quality of life.

PMID- 18038882
TI  - Development and validation of a patient-physician relationship index in the
      advanced cancer setting.
AB  - BACKGROUND: The quality of the relationship between patient and medical staff is
      crucial in oncological settings. We have developed and validated a short, self
      administered questionnaire to measure patients' satisfaction with their
      relationship with the physician: the Patient-Physician Relationship Index (PPRI).
      MATERIALS AND METHODS: Content validity was evaluated by a two-stage (development
      and judgment) process. One hundred and nine cancer patients with metastatic
      disease were assessed during the second cycle of chemotherapy and 59 were
      reassessed eight weeks later. Quality of life and anxiety and depression were
      also evaluated. RESULTS: The PPRI is monofactorial. Cronbach's alpha coefficient
      was 0.81. Sensitivity to change was shown by the correlation with changes in
      patients' conditions. The PPRI scores were only weakly correlated with the
      majority of the EORTC and HAD subscale scores. CONCLUSION: The PPRI is an easy-to
      use, self-administered questionnaire, developed in a population of patients with
      advanced cancer. It has good internal consistency and sensitivity to change.

PMID- 18038883
TI  - When should trastuzumab be stopped after achieving complete response in HER2
      positive metastatic breast cancer patients?
AB  - We report the case of a woman with HER2-positive metastatic breast cancer who
      achieved prolonged complete remission of multiple liver metastases after
      treatment with weekly trastuzumab plus paclitaxel but relapsed in the brain soon
      after stopping trastuzumab maintenance therapy which had been prosecuted for
      almost three years. In the absence of randomized trials, the optimal duration of
      trastuzumab administration after achieving complete remission of metastatic
      breast cancer remains questionable.

PMID- 18038884
TI  - Adenomyoepithelioma of the breast.
AB  - Adenomyoepithelioma of the breast is an uncommon tumor characterized by the
      presence of both epithelial and myoepithelial cells; its first full description
      was published in 1970 by Hamperl. A 45-year-old woman presented a left breast
      lump that had been palpable for 4 weeks. There was no family history of breast
      cancer. Neither axillary nor supraclavicular lymph nodes were palpable.
      Craniocaudal mammography showed a 1.6 cm, well-defined nodule with several
      punctate intranodular calcifications in the subareolar region of the left breast.
      Color Doppler sonogram showed an ovoid, well-defined, homogeneous hypoechoic
      subareolar nodule with prominent peripheral vessels in the 6 o'clock position of
      the left breast. Operation was arranged and intraoperative frozen section
      examination revealed proliferation of round, oval or tubular glandular elements
      with intervening islands and bands of polygonal myoepithelial cells.
      Adenomyoepithelioma of the breast was the impression. Wide excision with adequate
      removal of the tumor and preservation of the left breast contour was successfully
      achieved. The diagnosis of adenomyoepithelioma of the breast was confirmed by
      immunohistochemical studies.

PMID- 18038885
TI  - Primary neuroendocrine carcinoma of the breast: a case report.
AB  - Primary neuroendocrine carcinoma of the breast is an extremely rare tumor. We
      present our experience of primary neuroendocrine carcinoma of the breast in a 76
      year-old woman. Surgical biopsies from breast and axillary lymphadenopathy showed
      a neuroendocrine carcinoma. Immunohistochemical staining of tumor cells with
      GCDFP15, NSE and chromogranin were positive. Computed tomography scans of the
      chest and abdomen showed no lesion for metastasis or another primary origin.
      Adjuvant hormone therapy was given, since the tumor was immunohistochemically
      receptor positive.

PMID- 18038886
TI  - Neuroendocrine carcinomas of the upper airways: a small case series with
      histopathological considerations.
AB  - Neuroendocrine carcinomas are rare tumors. In the head and neck region they are
      most common in the larynx, where they represent 0.5-1% of epithelial cancers.
      Diagnosis requires the recognition of the typical neuroendocrine architecture and
      morphology and the immunohistochemical confirmation of neuroendocrine
      differentiation. In the 1991 WHO classification laryngeal neuroendocrine
      carcinomas have been divided into carcinoids, atypical carcinoids, small cell
      carcinomas and paragangliomas. Atypical carcinoids in the head and neck region
      usually show an aggressive behavior analogous to poorly differentiated
      carcinomas, and are resistant to chemo- and radiotherapy. For this reason, it was
      recently proposed to change their designation to "moderately differentiated
      neuroendocrine carcinomas". We present the clinical and histopathological
      features of 2 moderately differentiated neuroendocrine carcinomas of the larynx,
      one large cell poorly differentiated neuroendocrine carcinoma of the oropharynx,
      and one small cell carcinoma of the minor salivary glands of the tongue. The
      patient with small cell carcinoma was free from disease 26 months after radical
      surgery, while the other patients showed liver, lung and bone metastases 18, 26
      and 24 months after the diagnosis despite radical surgery or concomitant intra
      arterial chemotherapy and radiotherapy.

PMID- 18038887
TI  - Malignant fibrous histiocytoma associated with coxofemoral arthrodesis.
AB  - The discovery of biomaterials led to their use in the manufacture of implants for
      biomedical applications. In vivo, no metal or alloy is completely inert. The
      potential toxicity of some of the metals most frequently employed in the
      manufacture of orthopedic implants has been reported. Their carcinogenic
      potential has been evaluated in experimental animal models. However, few reports
      have discussed the potential development of malignant tumors associated with
      prosthetic structures in humans. The present study documents a case of
      intraosseous sarcoma that developed in the vicinity of a metallic prosthesis 43
      months after a coxofemoral arthrodesis with metallic pins and screws. With this
      report the authors seek to contribute to the understanding of the potential
      toxicity and risks of using metallic implants. Since metallic implants employed
      in the rehabilitation of osteo-muscular-articular disorders usually remain in the
      organism for long periods of time, the need to monitor the metallic structures
      and the adjacent tissues is extremely relevant.

PMID- 18038888
TI  - Solitary fibrous tumor of the anterior mediastinum: a rare extrapleural neoplasm.
AB  - Solitary fibrous tumors are uncommon spindle cell neoplasms originally thought to
      be restricted to the pleura. We describe a 62-year-old woman who presented with
      stridor and an anterior mediastinal mass. At thoracotomy, a 10.5 x 6.5 x 5.5 cm,
      circumscribed, firm mediastinal mass demonstrated no direct cardiac or pulmonary
      involvement. The tumor consisted of spindle cells organized in a patternless
      pattern with collagenous stroma and hemangiopericytoma-like vessels. Spindle
      cells were immunoreactive for CD34, CD99, desmin, vimentin and bcl-2 protein and
      a diagnosis of mediastinal solitary fibrous tumor was confirmed. The differential
      diagnosis of mediastinal solitary fibrous tumors is extensive and includes
      spindle cell thymoma, sarcomatoid carcinoma, malignant mesothelioma, inflammatory
      myofibroblastic tumor, peripheral nerve sheath tumors and various sarcomas.
      Despite their rarity in the mediastinum, solitary fibrous tumors can be
      recognized by their classic patternless morphology and immunophenotypic pattern.
      Their accurate classification is important, as solitary fibrous tumors are
      intermediate (rarely metastasizing) neoplasms that require complete surgical
      excision and long-term clinical follow-up for optimum therapy.

PMID- 18038889
TI  - Bone marrow metastasis of desmoplastic small round cell tumor.
AB  - Desmoplastic small round cell tumor is an extremely rare and highly aggressive
      neoplasm. It usually arises as a single mass or multiple masses in the abdominal
      cavity, characterized by diffuse peritoneal implants, involvement of regional
      lymph nodes, and liver and lung metastases. However, bone marrow metastasis has
      rarely been reported in the literature. We present a case of clinically
      symptomatic bone marrow metastasis in a 25-year-old woman with a diagnosis of
      desmoplastic small round cell tumor originating from the pelvic cavity.

PMID- 18038890
TI  - Nonsurgical treatment of an incompletely excised primary adenocarcinoma of
      nonpigmented ciliary epithelium.
AB  - Primary adenocarcinoma of the nonpigmented ciliary epithelium (NPCE) is a very
      rare disease and the majority of acquired cases were treated by enucleation. We
      report the case of a 19-year-old man who had an adenocarcinoma arising from the
      NPCE. The tumor was found incidentally due to changed pupil shape. An excisional
      biopsy was performed and histopathological examination showed primary
      adenocarcinoma of the NPCE with a positive resection margin. Because of the
      positive resection margin and to save the eye, radiotherapy rather than
      enucleation was performed, followed by chemotherapy. Two years after the
      diagnosis, the patient continues to be followed up without evidence of relapse or
      cataract change. Our case suggests that adjunctive radiotherapy should be
      considered as a sight-saving treatment modality for primary malignant tumors of
      the NPCE.

PMID- 18038891
TI  - Primary squamous cell carcinoma of the thyroid: immunohistochemical profile and
      literature review.
AB  - BACKGROUND: Squamous cell carcinoma accounts for 1% of primary thyroid
      malignancies and is characterized by a rapidly unfavorable outcome. CASE
      PRESENTATION: A 64-year-old woman presented with a painless mass in the left
      neck, coexisting with thyroid goiter. Total thyroidectomy with lymphadenectomy
      was performed and a primary thyroid squamous cell cancer was confirmed
      histologically after excluding any other possible primary malignancies. The
      tumor's immunohistochemical profile was explored using a large panel of
      antibodies. The tumor featured a positive immunoreaction to cytokeratins 7-19 and
      to squamous cell carcinoma antigen. Low-molecular-weight cytokeratins 5-6 and
      epithelial membrane antigen were also expressed. The neoplasm's proliferative
      index (Mib1) was 60%. No immunostaining was detected for cytokeratins 10-20,
      thyroglobulin, TTF-1, CD5, galectin-3 or p53. CONCLUSIONS: This case of primary
      thyroid squamous cell carcinoma immunohistochemically profiled using a large
      panel of immunoreactions may offer useful information on the histological
      differentiation of thyroid squamous cell carcinoma from other (uncommon) thyroid
      carcinomas and the distinction between primary and secondary thyroid cancers.

PMID- 18038893
TI  - Chemoradiotherapy in high-grade gliomas.

PMID- 18038892
TI  - Solid-cystic pseudopapillary tumor of pancreas: description of two cases and
      literature review.
AB  - The authors report the cases of two young female patients aged 17 and 27 years
      who underwent surgery for a rare tumor of the pancreas, Frantz's tumor or solid
      cystic pseudopapillary tumor. Solid-cystic pseudopapillary tumor of the pancreas
      is a rare tumor, accounting for 2.7% of pancreatic exocrine tumors. About 90% of
      these tumors occur in young women and they can reach very large dimensions. Due
      to their rareness and behavior, they are often associated with diagnostic and
      therapeutic problems. In most cases surgical treatment is curative and neither
      chemotherapy nor radiotherapy should be added. In the few cases where surgery is
      not possible, radiotherapy can be used because these tumors appear to be
      radiosensitive.

PMID- 18038894
TI  - [News on ASCO 2007. Sunitinib in the treatment of metastatic renal carcinoma and
      gastrointestinal stromal tumors].

PMID- 18038895
TI  - [How is the treatment changing in metastatic carcinoma of the colorectum].

PMID- 18038896
TI  - A new monoterpene glycoside from the roots of Paeonia lactiflora increases the
      differentiation of osteoblastic MC3T3-E1 cells.
AB  - A new monoterpene glycoside, 6'-O-beta-D-glucopyranosylalbiflorin (1), and four
      known compounds; albiflorin (2), 6'-O-benzoylalbiflorin (3), paeoniflorin (4) and
      benzoyl paeoniflorin (5), were isolated from the methanolic extract of the roots
      of Paeonia lactiflora Pall.. Their chemical structures were completely elucidated
      using a combination of 2D NMR techniques (COSY, HMQC and HMBC) and HRESI-MS
      analyses. To investigate the bioactivities of these compounds, their effects on
      the differentiation of osteoblastic MC3T3-E1 cells were tested. Compound 1 (0.01
      10 microM) significantly increased the alkaline phosphatase activity and nodules
      mineralization of MC3T3-E1 cells compared to those of the control (P<0.05). These
      results suggest that newly isolated compound 1 has a direct stimulatory effect on
      bone formation in vitro and may contribute to the prevention for osteoporosis.

PMID- 18038897
TI  - Synthesis and three-dimensional qualitative structure selectivity relationship of
      3,5-disubstituted-2,4-thiazolidinedione derivatives as COX2 inhibitors.
AB  - In our effort for synthesis of selective COX2 inhibitors, certain new 2,4
      thiazolidinedione derivatives were synthesized. It necessitates preparation of
      potassium salt of 2,4-thiazolidinedione 2, which condensed with intermediate 4a.
      The resulting 3-[2-(4-methylphenyl)-2-oxo-l-phenylethyl]-2,4-thiazolidinedione 8
      was condensed with appropriate aldehyde to afford compounds 10a, 10i-l, 10o and
      10p. Compounds (9a-l, 10a-n, 10p, 11 and 12) were obtained through the
      preparation of 5-arylmethylidene-2,4-thiazolidinediones 6a-p and reaction of its
      potassium salt 7a-p with compounds 4a, 4b, and 5. Some compounds displayed
      significant analgesic activity as compared to reference standards. The anti
      inflammatory activity of the synthesized compounds revealed that intermediate 8
      and compounds 9c, 10c and 10d showed good results. Compound 10c produced no
      significant mucosal injury. HipHop methodology of Catalyst program was used to
      build up hypothetical model of selective COX2 inhibitors followed by fitting the
      synthesized compounds to this model. Compounds 10c and 10d were suspected to be
      promising selective COX2 inhibitors. Also, compounds (6c, 8, 9a,c,d,k, 10a,c,d,k,
      11 and 12) were docked into COX1 and COX2 X-ray structures, using DOCK6 program.
      Docking results suggested that several of these derivatives are active COX
      inhibitors with a significant preference for COX2.

PMID- 18038898
TI  - Alternative and improved syntheses of highly potent and selective A3 adenosine
      receptor agonists, Cl-IB-MECA and thio-Cl-IB-MECA.
AB  - Improved syntheses of potent and selective A3 adenosine receptor agonists, Cl-IB
      MECA and thio-Cl-IB-MECA were accomplished from cheap stating material, D-ribose.
      New synthetic methods were found to be superior to old methods from the viewpoint
      of use of cheap starting material, number of steps, and overall yields.

PMID- 18038899
TI  - Structure-activity relationships of 6-hydroxy-7-methoxychroman-2-carboxylic acid
      N-(substituted)phenylamides as inhibitors of nuclear factor-kappaB activation.
AB  - A series of 6-hydroxy-7-methoxychroman-2-carboxylic acid N
      substitutedphenylamides (2a-n) were synthesized and their ability to inhibit
      nuclear factor-kappaB activity was evaluated in lipopolysaccharide (LPS)
      stimulated macrophage RAW 264.7 cells. While compounds bearing -OH, or -OCH3
      substituents were inactive, compounds with -CH3, -CF3, or -Cl substituents were
      potent inhibitors (IC50: 6.0-60.2 microM). The most active compound, 2n,
      contained a 4-Cl substituent on the phenyl ring and was four times more potent
      than the compound KL-1156.

PMID- 18038900
TI  - Apoptosis-mediated cytotoxicity of ouabain, digoxin and proscillaridin A in the
      estrogen independent MDA-MB-231 breast cancer cells.
AB  - We examined the effects of three cardiac glycosides, ouabain, digoxin and
      proscillaridin A, on the proliferation of estrogen independent MDA-MB-231 breast
      cancer cells. In terms of reduction in cell viability, the compounds rank for
      both 24 h and 48 h of incubation in MDA-MB-231 cells in the order proscillaridin
      A > digoxin > ouabain. Digoxin for 24 h and 48 h of incubation in MDA-MB-231
      cells proved to be only slightly more potent than ouabain, with IC50 values of
      122 +/- 2 and 70 +/- 2 nM, respectively, compared to 150 +/- 2 and 90 +/- 2 nM
      for ouabain. In contrast, proscillaridin A, was much more active and showed a
      high level of cytotoxic potency, IC50 51 +/- 2 and 15 +/- 2 nM for 24 h and 48 h
      of incubation, respectively. The concentrations of digoxin, ouabain and
      proscillaridin A needed to inhibit [3H]thymidine incorporation into DNA by 50%
      (IC50) in MDA-MB-231 cells for 24 h of incubation were found to be 124 +/- 2 nM,
      142 +/- 2 nM, and 48 +/- 2 nM, respectively. In the present study, we
      demonstrated that ouabain, digoxin, and proscillaridin A induce apoptosis in MDA
      MB-231 cells by increasing free calcium concentration and by activating caspase
      3.

PMID- 18038901
TI  - Estrogen attenuates cardiac ischemia-reperfusion injury via inhibition of calpain
      mediated bid cleavage.
AB  - Although several studies have shown that the administration of 17beta-estradiol
      (estrogen) is cardioprotective to ischemia-reperfusion (I/R), the molecular
      mechanisms are largely unknown. Therefore, we investigated the effects of
      estrogen on myocardial I/R injury in rat that were sham operated (Sham),
      ovariectomized (OVX), or ovariectomized and then given estrogen supplementation
      (OE). Langendorff-perfused rat hearts were subjected to I/R stimuli and the
      effects of estrogen were examined on cardiac performance. Additionally, we
      examined the mechanism of estrogen-mediated inhibition of apoptosis. Depression
      in cardiac contractile function and an increment of calpain activity were
      observed during I/R in the OVX rats. Estrogen replacement recovered cardiac
      contractile function and attenuated calpain activity, Bid cleavage, and caspases
      activities. Through in vitro assay using cardiomyocytes, we demonstrated that
      addition of H2O2 (100 microM) significantly increased calpain activity, which was
      attenuated by estrogen. Moreover, calpain activity was inhibited by calpain
      inhibitors such as ALLN or leupeptin, but not by caspase-8 inhibitor peptide.
      These results suggest that estrogen protects the heart against I/R injury through
      the decrease of calpain activity, Bid cleavage and caspase-8 activity. These
      apoptotic mechanisms may play a critical role on I/R-associated cardiac damage.

PMID- 18038902
TI  - Inhibition of inducible prostaglandin E2 production and cyclooxygenase-2
      expression by curdione from Curcuma zedoaria.
AB  - Overproduction of prostaglandins has been considered in mediation of inflammation
      and carcinogenic process. On this line, the inhibitors of prostaglandin
      biosynthetic enzyme cyclooxygenase (COX) have played a role of anti-inflammatory
      and cancer chemopreventive agents. In our continuous efforts to search anti
      inflammatory and chemopreventive agents from natural products, bioassay-guided
      fractionation led to the isolation of curdione from the rhizome of Curcuma
      zedoaria with the inhibitory effect on the production of prostaglandin E2 in
      lipopolysaccharide (LPS)-stimulated mouse macrophage RAW 264.7 cells in a
      concentration-dependent manner (IC50 = 1.1 microM). Mechanistic studies suggest
      that the suppression of cyclooxygenase-2 (COX-2) mRNA expression is, at least in
      part, involved in this inhibitory activity of curdione.

PMID- 18038903
TI  - Influence of polyphenolic compounds isolated from Rubus coreanum on catecholamine
      release in the rat adrenal medulla.
AB  - The aim of the present study was to investigate whether polyphenolic compounds
      isolated from wine brewed from Rubus coreanum MIQUEL (PCRC) may affect the
      release of catecholamine (CA) from the isolated perfused rat adrenal medulla, and
      to establish its mechanism of action. PCRC (20-180 microg/mL) perfused into an
      adrenal vein for 90 min dose- and time-dependently inhibited the CA secretory
      responses evoked by acetylcholine (ACh, 5.32 mM), high K+ (a direct membrane
      depolarizer, 56 mM), DMPP (a selective neuronal nicotinic Nn receptor agonist,
      100 microM) and McN-A-343 (a selective muscarinic M1 receptor agonist, 100
      microM). Also, in the presence of PCRC (60 microg/mL), the secretory responses of
      CA evoked by Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10
      microM), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 microM)
      were significantly reduced, respectively. In the simultaneous presence of PCRC
      (60 microg/mL) and L-NAME (an inhibitor of NO synthase, 30 microM), the
      inhibitory responses of PCRC on the CA secretion evoked by ACh, high K+, DMPP,
      and Bay-K-8644 were considerably recovered to the extent of the corresponding
      control secretion compared with the inhibitory effect of PCRC alone. Taken
      together, these results obtained from the present study demonstrate that PCRC
      inhibits the CA secretory responses from the isolated perfused adrenal gland of
      the normotensive rats evoked by stimulation of cholinergic (both muscarinic and
      nicotinic) receptors as well as by direct membrane-depolarization. It seems that
      this inhibitory effect of PCRC is exerted by inhibiting both the calcium influx
      into the rat adrenal medullary chromaffin cells and the uptake of Ca2+ into the
      cytoplasmic calcium store partly through the increased NO production due to the
      activation of nitric oxide synthase (NOS), which are at least relevant to the
      direct interaction with the nicotinic receptor itself. It is also thought that
      PCRC might be effective in prevention of cardiovascular disease.

PMID- 18038904
TI  - Effects of Korean mistletoe lectin (Viscum album coloratum) on proliferation and
      cytokine expression in human peripheral blood mononuclear cells and T
      lymphocytes.
AB  - The anti-cancer activity of mistletoe has been ascribed to a combination of
      cytotoxic and immunological effects. We previously showed that Korean mistletoe
      lectin (Viscum album L. var. coloratum agglutinin, VCA) can stimulate IFN-gamma
      production and modulate proliferation in murine splenocytes. In this study, we
      investigated the effects of VCA on human peripheral blood mononuclear cells
      (hPBMC) and T-lymphocytes. The addition of VCA resulted in a significant
      inhibition of proliferation at higher concentrations (at 2-8 ng/mL, 1-8 ng/mL in
      hPBMC and T-lymphocytes, respectively) but an induction at lower concentrations
      (at 4-16 pg/mL, 4-32 pg/mL in hPBMC and T-lymphocytes, respectively). Further
      studies were carried out to determine if the pro-proliferative or anti
      proliferative activity exhibited by VCA was correlated with apoptosis and
      cytokine secretion. As a result, the apoptotic cell number increased to 26% after
      48 h of VCA treatment (10 ng/mL) in the presence of anti-CD3/CD28 antibodies. On
      the other hand, without anti-CD3/CD28 antibody stimulants, VCA did not arrest
      cell cycle. In addition, it was shown that VCA could induce IL-2 secretion was
      dose-dependently increased by VCA in stimulated (anti-CD3/CD28 antibodies) (at
      0.25-2 ng/mL) and non-stimulated (at 3-25 pg/mL) human T-lymphocytes. Also, at
      low and non-toxic concentrations of VCA, the RT-PCR result confirmed the release
      of pro-inflammatory cytokines such as IL-1alpha, IL-1beta, IL-6, IL-8, and IFN
      gamma. These data may suggest new perspective to modulate the balance between
      cell growth, cytokine production and programmed cell death therapeutically.

PMID- 18038905
TI  - Immunosuppressive effect of silibinin in experimental autoimmune
      encephalomyelitis.
AB  - Silibinin is the major pharmacologically active compound of silymarin, the
      Silybum marianum fruit extract. Hepatoprotective activities of
      silibinin/silymarin are well-known, and recent studies demonstrated their anti
      inflammatory and anti-carcinogenic effects which are due to inhibition of the
      transcription factor NF-kappaB. Based on this knowledge, we hypothesized that
      silibinin could be effective in the treatment of multiple sclerosis (MS) and so
      we tested its immunosuppressive effect in experimental autoimmune
      encephalomyelitis (EAE), the MS animal model. The process of spinal cord
      demyelination and inflammation were observed and T cell migration was determined
      by FACS analysis. The results showed that silibinin significantly reduced the
      histological signs of demyelination and inflammation in EAE. Since cytokines play
      an important role in inflammatory disease, the proliferative response and
      cytokine production were examined in lymphocytes from spleens and lymph nodes. We
      demonstrated that silibinin Ag-nonspecifically down-regulated the secretion of
      pro-inflammatory Th1 cytokines and up-regulated the anti-inflammatory Th2
      cytokines in vitro. Silibinin also dose-dependently inhibited the production of
      Th1 cytokines ex vivo. These results indicate that silibinin is both
      immunosuppressive and immunomodulatory.

PMID- 18038906
TI  - Moving cell bodies: understanding the migratory mechanism of facial motor
      neurons.
AB  - Facial branchiomotor (FBM) neurons innervate facial musculature to control facial
      and jaw movement, which is crucial for facial expressions, speaking, and eating.
      FBM neurons are one of the largest populations among cranial motor neuronal class
      forming distinct nucleus in the hindbrain. To construct functional FBM neuronal
      system, a variety of cellular and molecular mechanisms play a role during
      embryonic development and thereby present a good framework for understanding the
      principles of neural development. Over the past decade, genetic approaches in
      mice and zebrafish have provided a better understanding of molecular pathways for
      FBM neuron development. This review will focus on regulatory mechanisms for cell
      body movement of FBM neurons, one of the unique features of FBM neuronal
      development. First, I will describe the basic anatomy of hindbrain, organization
      of cranial motor neurons, and developmental sequence of FBM neurons in
      vertebrates. Next, I will focus on the migratory process of FBM neurons in detail
      in conjunction with recent genetic evidence for underlying regulatory mechanisms,
      candidate environmental signals, and transcription factors for FBM neuronal
      development.

PMID- 18038907
TI  - N-acetylcysteine prevents LPS-induced pro-inflammatory cytokines and MMP2
      production in gingival fibroblasts.
AB  - Periodontitis is an inflammatory process that ultimately results in tooth loss.
      Although the primary etiologic agent for periodontitis is bacteria, the majority
      of periodontal tissue destruction is thought to be caused by an inappropriate
      host response. Reactive oxygen species (ROS) have been known to be involved in
      periodontal tissue destruction. We treated human gingival fibroblasts with
      lipopolysaccharide (LPS) obtained from E. coli and the periodontopathogens
      Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, and examined
      their inflammatory responses in the presence and absence of the antioxidant N
      acetylcysteine (NAC). LPS enhanced ROS production, as well as, expression of pro
      inflammatory cytokines such as interleukin-1beta, interleukin-6, interleukin-8
      and tumor necrosis factor-alpha, and the production and activation of MMP2. NAC
      suppressed all LPS-induced inflammatory responses examined, suggesting that LPS
      induced ROS may play a major regulatory role in these responses in gingival
      fibroblasts. In addition, NAC prevented LPS-induced activation of p38 MAPK and
      JNK but not phosphorylation and subsequent degradation of IkB. These results
      indicate that NAC exerts anti-inflammatory effects in LPS-stimulated gingival
      fibroblasts, functioning at least in part via down-regulation of JNK and p38 MAPK
      activation. Furthermore, this work suggests that antioxidants may be useful in
      adjunctive therapies that complement conventional periodontal treatments.

PMID- 18038908
TI  - Anti-oxidative and photo-protective effects of coumarins isolated from Fraxinus
      chinensis.
AB  - Free radicals and reactive oxygen species (ROS), which are generated by UV
      irradiation, may cause serious injury to skin cell membranes, DNA and functional
      proteins. In addition, these agents stimulate the expressions of matrix
      metalloproteinases (MMPs), which can degrade most components of the extracellular
      matrix (ECM), including collagen. In order to develop new anti-photoaging agents,
      five major components from the extract of Fraxinus chinensis extract (FCE) were
      identified. Two of the major components of FCE were found to be esculin (11.2%)
      and esculetin (1.9%). FCE (IC50: 50.0 microg/mL 1, 1-diphenyl-2-picrylhydrazyl
      (DPPH); 19.8 microg/mL, superoxide anion radical) and esculetin (IC50: 2.1
      microg/mL DPPH; 0.6 microg/mL, superoxide anion radical) showed strong
      antioxidative activities. Of the compounds tested, esculetin showed the strongest
      scavenging activity against DPPH radicals, followed by superoxide anions from the
      xanthine/xanthine oxidase system. The intracellular ROS scavenging activity
      showed that oxidation of 5-(6-)-chloromethyl-2', 7'-dichlorodihydrofluorescein
      diacetate (CM-H2DCFDA) was effectively inhibited by esculetin, with potent free
      radical scavenging activity was also shown in UVB-irradiated human dermal
      fibroblasts (HDFs). Moreover, treatment of UVA-irradiated HDFs with esculetin
      resulted in dose-dependent decreases in the expression levels of MMP-1 mRNA and
      protein. From these results, FCE and one of its components, esculetin, were
      predicted to be potentially useful as ingredients in cosmetics for protecting
      against photoaging.

PMID- 18038909
TI  - Purification and biochemical properties of phospholipase D (PLD57) produced by
      Streptomyces sp. CS-57.
AB  - Streptomyces sp. CS-57, which was isolated from Korean soil, was found to produce
      phospholipase D (PLD57) as an extracellular enzyme when cultured in medium
      containing 2% glucose, 1.5% yeast extract, 0.5% trypton, and 0.1% calcium
      carbonate at 28 degrees C, and 160-rpm. PLD57 was purified using Sepharose CL-6B
      column chromatography, and DEAE-Sepharose CL-6B ion exchange column
      chromatography. The specific activity of the purified enzyme increased 6.7 fold
      with 3% recovery. The purified enzyme was then analyzed using 12% SDS-PAGE, which
      revealed that the molecular mass of the purified enzyme was 55 kDa. PLD57 showed
      both hydrolytic (H) and transphosphatidylation (T) activity, and the optimum
      temperatures of these activities were found to be 45 degrees C and 35 degrees C,
      respectively. Similarly, both of these activities were found to be optimal at a
      pH of 7.5. In addition, even after being heat treated at 45 degrees C for up to 2
      h, the enzyme activity remained at 100%, and the H-activity was found to be
      stable at a pH of 6 to 8. Further, enzyme activity occurred in the presence of
      EDTA, indicating that metal ions are not required for their activity, although
      some metal ions did marginally increase the activity. Enzyme activity also
      increased by 75% in the presence of Triton-X 100 at a concentration of 0.375 %;
      however, none of the other detergents evaluated in this study were found to
      enhance enzyme activity.

PMID- 18038910
TI  - Protective effects of puerarin on carbon tetrachloride-induced hepatotoxicity.
AB  - Puerarin, the main isoflavone glycoside found in the root of Pueraria lobata, has
      been used for various medicinal purposes in traditional Chinese medicine for
      thousands of years. The purpose of this study was to investigate the protective
      effects of puerarin against hepatotoxicity induced by carbon tetrachloride (CCl4)
      and the mechanism of its hepatoprotective effect. In mice, pretreatment with
      puerarin prior to the administration of CCl4 significantly prevented the
      increased serum enzymatic activity of alanine aspartate aminotransferase and
      hepatic malondialdehyde formation in a dose-dependent manner. In addition,
      pretreatment with puerarin significantly prevented both the depletion of reduced
      glutathione (GSH) content and the decrease in glutathione S-transferase (GST)
      activity in the liver of CCl4-intoxicated mice. Hepatic GSH levels and GST
      activity were increased by treatment with puerarin alone. CCl4-induced
      hepatotoxicity was also prevented, as indicated by liver histopathology. The
      effects of puerarin on cytochrome P450 (CYP) 2E1, the major isozyme involved in
      CCl4 bioactivation, were also investigated. Treatment of the mice with puerarin
      resulted in a significant decrease in the CYP2E1-dependent aniline hydroxylation
      in a dose-dependent manner. Consistent with these observations, the CYP2E1
      protein levels were also lowered. Puerarin exhibited anti-oxidant effects on
      FeCl2-ascorbate induced lipid peroxidation in mouse liver homogenates, and on
      superoxide radical scavenging activity. These results suggest that the protective
      effects of puerarin against the CCl4-induced hepatotoxicity possibly involve
      mechanisms related to its ability to block CYP-mediated CCl4 bioactivation,
      induction of GST activity and free radical scavenging effects.

PMID- 18038912
TI  - Mechanism of apoptosis induced by apigenin in HepG2 human hepatoma cells:
      involvement of reactive oxygen species generated by NADPH oxidase.
AB  - Although plant-derived flavonoids have been reported to have anti-cancer
      activities, the exact mechanism of these actions is not completely understood. In
      this study we investigated the role for reactive oxygen species (ROS) as a
      mediator of the apoptosis induced by apigenin, a widespread flavonoid in plant,
      in HepG2 human hepatoma cells. Apigenin reduced cell viability, and induced
      apoptotic cell death in a dose-dependent manner. In addition, it evoked a dose
      related elevation of intracellular ROS level. Treatment with various inhibitors
      of the NADPH oxidase (diphenylene iodonium, apocynin, neopterine) significantly
      blunted both the generation of ROS and induction of apoptosis induced by
      apigenin. These results suggest that ROS generated through the activation of the
      NADPH oxidase may play an essential role in the apoptosis induced by apigenin in
      HepG2 cells. These results further suggest that apigenin may be valuable for the
      therapeutic management of human hepatomas.

PMID- 18038913
TI  - Formulation and evaluation of less-painful clarithromycin lipid microspheres.
AB  - Lipid microspheres (LMs) have recently been use as drug carriers for intravenous
      use due to its low toxicity, good physiological tolerance and the reduction of
      the drug related side-effect. In this study, clarithromycin was incorporated in
      LMs, in an attempt to reduce the pain caused by intravenous use. The composition
      of the drug loaded LMs was clarithromycin 0.5%, oil phase 10%, soybean
      phospholipid 2%, egg lecithin 0.5%, Sodium oleate 0.1%. Clarithromycin LMs was
      prepared by high pressure homogenization method at 80 MPa for 8-10 cycles. The
      mean particle size and surface charge of LMs were 208.7+/-7.8 nm and -23.6+/-2.3
      mv respectively. Clarithromycin entrapment efficiency in LMs was 66.4%. Drug
      loaded LMs was stable during the storage time at 6+/-2 degrees C for 9 month, and
      the particle size and zeta-potential did not change significantly. Drug
      concentration in LMs was 5 mg/mL, and there was no drug degradation during long
      term storage. Animal tests (rat paw lick test and rabbit ear vein irritation
      test) were used to evaluate the pain reduction of clarithromycin LMs compared
      with that of clarithromycin aqueous solution. These results suggest that the LM
      system is a promising option to replace clarithromycin aqueous solutions as an
      intravenous treatment.

PMID- 18038911
TI  - Anti-inflammatory mechanisms of apigenin: inhibition of cyclooxygenase-2
      expression, adhesion of monocytes to human umbilical vein endothelial cells, and
      expression of cellular adhesion molecules.
AB  - The aim of this study was to clarify the anti-inflammatory mechanism of apigenin.
      Apigenin inhibited the collagenase activity involved in rheumatoid arthritis (RA)
      and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a
      dose dependent manner in RAW 264.7 macrophage cells. Pretreatment with apigenin
      also attenuated LPS-induced cyclooxygenase-2 (COX-2) expression. In addition,
      apigenin profoundly reduced the tumor necrosis factor-alpha (TNF-alpha)-induced
      adhesion of monocytes to HUVEC monolayer. Apigenin significantly suppressed the
      TNF-alpha-stimulated upregulation of vascular cellular adhesion molecule-1 (VCAM
      1)-, intracellular adhesion molecule-1 (ICAM-1)-, and E-selectin-mRNA to the
      basal levels. Taken together, these results suggest that apigenin has significant
      anti-inflammatory activity that involves blocking NO-mediated COX-2 expression
      and monocyte adherence. These results further suggest that apigenin may be useful
      for therapeutic management of inflammatory diseases.

PMID- 18038914
TI  - Mixed micellar nanoparticle of amphotericin B and poly styrene-block-poly
      ethylene oxide reduces nephrotoxicity but retains antifungal activity.
AB  - Mixed micellar nanoparticle consisting of amphotericin B (AmB) and poly styrene
      block-poly ethylene oxide (PS-block-PEO) was prepared by high pressure
      homogenizer. Nephrotoxicity of the nanoparticle was investigated along with
      antifungal activity and self-aggregation status of the drug in the nanoparticle.
      Nephrotoxicity was markedly reduced when AmB was intravenously administered to
      rats as mixed micellar nanoparticle with PS-block-PEO in terms of transmission
      electron microscopy of tubular cells and creatinine clearance. Antifungal
      activity of AmB was not altered when the drug was in the form of mixed micellar
      nanoparticle compared to both conventional formulation and AmB micelle treated by
      same procedure without PS-block-PEO. Self-aggregation status of AmB molecules
      revealed monomeric in the mixed micellar nanoparticle with PS-block-PEO up to the
      therapeutic level of the drug (1-3 mM). The reduced nephrotoxicity of AmB in
      mixed micellar nanoparticle may be associated with the existence of the drug as
      monomeric form in the nanoparticle. Based on our result, formulation of AmB as
      mixed micellar nanoparticle with PS-block-PEO may be a promising alternative for
      the treatment of fungal diseases in patients who are at risk of renal
      dysfunction.

PMID- 18038916
TI  - Pulmonary arterial hypertension secondary to chronic lung diseases: pathogenesis
      and medical treatment.
AB  - Pulmonary artery hypertension secondary to chronic lung diseases is a clinical
      entity with no specific symptoms that can develop as a result of parenchymal lung
      disorders (COPD-emphysema, sleep apnea syndrome, diffuse parenchymal lung
      diseases, etc.) and pulmonary vascular disorders (vasculitis, sarcoidosis, etc.).
      In the clinical history of these chronic and invalidating diseases, pulmonary
      vasculature goes through various degenerative and/or proliferative changes,
      responsible of the pulmonary arterial hypertension appearance. The rise in
      pulmonary artery pressure can be subtle and the progression from an asymptomatic
      disease to a more severe syndrome is often common in all forms of secondary
      pulmonary arterial hypertension. Etiopathology of pulmonary artery hypertension
      secondary to chronic lung diseases is based on one or more of the following
      mechanisms: hypoxic vasoconstriction, decreased area of pulmonary vascular bed,
      volume/pressure overload. In these forms, the above three mechanisms show common
      mediators, all responsible of disease progression but singularly potential
      reversible. Therapies for secondary pulmonary artery hypertension consist
      primarily on the treatment of the underlying disease. Therapy is most effective
      when initiated prior to the onset of irreversible pulmonary vascular damage. In
      the last two decades, new medical treatments (prostacyclins, endothelin receptor
      antagonists, phosphodiesterase inhibitors) for pulmonary arterial hypertension
      have been available for the sporadic and the secondary to systemic sclerosis
      forms. The role of these drugs in the other forms of pulmonary arterial
      hypertension has not been well studied yet. This review will go through the
      pathogenesis and the several therapeutic approaches for pulmonary artery
      hypertension secondary to chronic pulmonary diseases or pulmonary vasculature
      disorders.

PMID- 18038915
TI  - A liquid chromatographic method for the determination of histamine in
      immunoglobulin preparation using solid phase extraction and pre-column
      derivatization.
AB  - An immunoglobulin (IgG) preparation with micro-amount of histamine fixed on the
      active protein fraction has been used to increase the resistance to allergic
      reactions. However, excessive histamine may cause hypo- or hypertension,
      headache, or anaphylactic shock and so the histamine content of the drug is
      strictly controlled by a regulation: 0.15 microg of histamine dihydrochloride is
      allowed for 12 mg of immunoglobulin. In this study, a liquid chromatographic
      method to determine micro-amount of histamine in the pharmaceutical was developed
      and validated. This method include a sample cleanup by a solid phase extraction
      (SPE) using a polystyrene-divinyl benzene (PS-DVB) polymeric sorbent and high
      performance liquid chromatography after precolumn fluorescent labeling of the
      histamine with o-phthaldialdehyde. The drug sample was loaded to the SPE
      cartridge after adjusting to pH 9.5. After successive washings of the cartridge
      with water and 30% aqueous methanol, histamine was then eluted with 100 mM sodium
      acetate (pH 9.5)-methanol (20:80, v/v). An aliquot from the eluate was labeled
      with o-phthaldialdehyde-mercaptoethanol (OPA-ME) for fluorescence detection at
      the excitation maximum of 340 nm and emission maximum of 450 nm. HPLC analysis
      was performed on a phenyl-hexyl column with an acetonitrile-phosphate buffer (pH
      6.8; 50 microM) (35:65, v/v) as the mobile phase. The retention times of
      histamine and 3-methylhistamine (IS) were approximately 7.2 and 9.5 min,
      respectively. The quantitation range was between 0.01-0.2 mg/mL of histamine
      showing good linearity (r=0.9996). This analytical method would provide a
      potential mean for the strict control of histamine content in the pharmaceutical
      product.

PMID- 18038917
TI  - Comparative analysis of DR and DQ alleles occurrence in sarcoidosis and
      tuberculosis in the same ethnic group: preliminary study.
AB  - BACKGROUND: Pathologic similarities between sarcoidosis (SA) and tuberculosis
      (TB) suggest M. tuberculosis antigen(s) as causative agents. It seems likely that
      in the genetically different predisposed hosts, the same antigen(s) may cause the
      development of sarcoid or tuberculous Th1 response. AIM AND MATERIALS/METHODS: To
      test a difference in haplotypes associated with both diseases, we compared the
      distribution of DRB1, DQA1 and DQB1 alleles in 45 SA patients, 62 TB patients and
      in 143 healthy volunteers, using a PCR-SSP method. RESULTS: Our results revealed
      that DRB1*03/*11, DQB1*02, DQA*0501 in Stage I of SA with Lofgren's syndrome (Ls)
      and DRB1*15, DQA1*0102/*0103 in Stage II of SA were more common, whereas
      DQA1*0102 (Ls) and DRB1*16/*04/*08, DQB1*03/*04/*05/*06, DQA1*0301 (Ls, Stage II)
      were less common than in the controls. Nevertheless, after Bonferroni correction,
      only DRB1*04, DQB1*02/*03/*05/*06, DQA1*0102/*0301/*0501 differed significantly.
      In TB group, DRB1*16/*14, DQB1*05, DQA1*0303 were more frequent and DRB1*11,
      DQB1*02, DQA1*0201/*0505 less frequently present as compared to the controls, but
      frequency of DRB1*16, DQB1*02/*05 and DQA1*0303/*0505 only was significantly
      different after correction. After correction in both Stages of SA, DRB1*11 was
      more common and DRB1*16/*04/*14, DQB1*03/*05, DQA1*0301/0302/*0303 were less
      frequent than in the TB group. DQB1*02, DQA1*0201/*0501 (Ls) and DRB1*15/*13
      (Stage II) were more frequently present in SA than in TB, but after correction,
      only DRB1*15, DQB1*02, DQA1*0501 were significantly different. CONCLUSIONS: We
      identified associations of HLA class II alleles in SA and TB with expression
      pattern specific and different for each group. In most cases, in SA patients
      frequency of HLA class II alleles occurrence is opposite to the frequency in TB
      patients.

PMID- 18038918
TI  - Enhanced proliferation and decreased apoptosis in lung lavage cells of
      sarcoidosis patients.
AB  - BACKGROUND: Sarcoidosis is a systemic autoimmune disease where an inflammatory
      reaction involving alveolar macrophages, T-helper lymphocytes, and epitheloid
      cells is mounted against unknown antigens. A genetic predisposition for
      sarcoidosis is supposed by studies in twins, by geographical and racial
      distribution. In the current investigation we compared the expression patterns
      between slow onset and acute sarcodosis using a whole-genome cDNA array. METHODS:
      Bronchoalveolar lavage was performed in six patients with slow onset sarcoidosis
      and four patients with acute sarcoidosis (Lofgren's disease) and obtained cells
      were used for gene expression profiling. The results were confirmed by RT- and
      Taqman-PCR. In addition, protein expression was examined on paraffin sections of
      sarcoid granulomas by immunohistochemistry. RESULTS: In T-helper lymphocytes and
      alveolar macrophages we found an upregulation of genes belonging to the
      phosphoinositol-3-kinase/v-akt murine thymoma viral oncogene homolog/signal
      transducer and activator of transcription 3 pathway, as well as a downregulation
      of genes of the extrinsic and intrinsic apoptotic signaling cascades. In addition
      an upregulation of the genes encoding fatty acid binding protein 4 and 5, as well
      as peroxisome proliferative activated receptor delta in Lofgren's disease was
      detected. Differences in gene expression between slow onset sarcoidosis and
      Lofgren's syndrome were found mainly within genes of the major histocompatibility
      complex. CONCLUSIONS: In sarcoidosis enhanced cell proliferation and decreased
      apoptosis result in accumulation and prolonged survival of antigen-primed T
      helper lymphocytes and activated macrophages. This is enhanced in Lofgren's
      disease, probably by hyper-stimulation via the peroxisome proliferation
      signaling, providing a larger pool of antigen-primed immune cells.

PMID- 18038919
TI  - A double-blinded, randomized, placebo-controlled trial of infliximab in subjects
      with active pulmonary sarcoidosis.
AB  - STUDY OBJECTIVES: To evaluate the safety and tolerability of infliximab in the
      treatment of active pulmonary sarcoidosis, and to provide an initial assessment
      of the efficacy of infliximab in the treatment of active pulmonary sarcoidosis.
      DESIGN: Double-blind, randomized, placebo-controlled phase II study. SETTING:
      Multicenter. PATIENTS: Active Radiographic Stage II, III, and IV active pulmonary
      sarcoidosis despite corticosteroids or previous intolerance to corticosteroids.
      INTERVENTION: Infliximab 5mg/kg (group I) or placebo (group II) at weeks 0 and 2
      and open-label infliximab 5mg/kg for all subjects at weeks 6 and 14.
      MEASUREMENTS: Pulmonary function, chest radiographs, dyspnea stage, SF-36.
      RESULTS: Mean vital capacity (VC) at wk 0 was 2.47 +/- 0.2 (group I) and 2.37 +/-
      0.31 (group II). At 6 weeks the mean +/- SD relative change in VC compared to
      baseline was 15.22 +/- 9.91% for group I (n=13) and 8.39 +/- 3.33% for group II
      (n=6) (p=0.65). Four patients had serious adverse events, including decreased WBC
      and elevated CPK (1 patient), pneumonia (1 patient), cellulitis, acute renal
      failure, pulmonary embolus and death (1 patient), and visual field defect (1
      patient). CONCLUSIONS: Infliximab may improve VC in patients with active PS
      resistant to steroids. Larger scale, longer term studies will be needed to assess
      both safety and efficacy.

PMID- 18038920
TI  - Long term prognosis of sarcoidosis in Arabs and Asians: predictors of good
      outcome.
AB  - BACKGROUND: The prognosis of sarcoidosis is variable and often difficult to
      predict. Our aim was to identify predictors of good prognosis in Arabs and Asians
      with sarcoidosis. METHODS: Data on patients with sarcoidosis followed up for at
      least 3 years in two major hospitals in Kuwait were collected retrospectively for
      the period 1983 to 1995 and prospectively from 1995. RESULTS: Of the total 115
      patients, 60% were females and 80% were Arabs. Majority, 86.9%, of the patients
      had either Stage I or II disease. Forty-five (43.7%) were followed up for 3 to 5
      years, 43 (41.7%) for 5 to 9 and 15 (14.6%) for 10 or more years while 12 were
      lost to follow up. Good prognosis was seen in 53 (51%), intermediate in 33(32%)
      and poor in 17 (17%) patients. Two patients (1.9%) died. Good prognosis was
      observed in 74.4% of patients with Stage I, 40% of patients with Stage II and
      16.7% with stage III disease, p = 0.001. In addition, presence of arthralgia
      predicted a good prognosis, p = 0.014. Hypercalcemia was noted only in patients
      with poor or intermediate outcome. Gender, ethnicity, and presence of erythema
      nodosum were not predictors of prognosis in our patients. Multivariate logistic
      regression analysis confirmed that early stage of the disease [OR (95 %CI), 6.1
      (2.3-15.7), p = 0.001] and presence of arthralgia, [OR (95%CI), 4.5 (1.3-15.4), p
      = 0.02] were predictors of good prognosis. CONCLUSION: Presence of arthralgia and
      early stage of the disease were the most important predictors of good prognosis.
      Sex, age, ethnicity and presence of erythema nodosum did not influence the
      prognosis.

PMID- 18038921
TI  - Chronic beryllium disease among dental technicians in Israel.
AB  - BACKGROUND AND AIM: The potential risks of beryllium use in the dental industry
      have been recognized for some time. This is the first case series that focuses on
      the effect of a number of potentially harmful effects of substances that induce
      lung disease among dental technicians with emphasis on beryllium as a major risk
      factor in the work environment of dental technicians. METHODS: All the dental
      technicians consecutively recruited to this study had past occupational exposure
      to beryllium. They were evaluated in order to confirm immunological evidence of
      beryllium exposure for differential diagnosis between sarcoidosis and chronic
      beryllium disease (CBD). They were tested for beryllium sensitization by the
      beryllium lymphocyte proliferation test (BeLPT), and underwent lung function and
      induced sputum (IS) studies. Each had earlier undergone a comprehensive
      evaluation that included high-resolution computerized tomography, bronchoscopy
      and transbronchial biopsy to establish the final diagnosis of their condition.
      RESULTS: There were 24 enrollees (mean age 49.7 +/- 13.7 years, 17 males, 7
      females) of whom 12 (50%) had positive BeLPT findings and were finally diagnosed
      as suffering from CBD, 7 (29%) had negative BeLPT findings and were diagnosed as
      suffering from another pulmonary pathology (sarcoidosis, chronic obstructive
      pulmonary disease, rejection of transplanted lung), and 5 (20.8%) had negative
      BeLPT findings and were diagnosed as being free of pulmonary disease. CONCLUSION:
      This case series study demonstrates that dental technicians are exposed to
      beryllium and various other occupational dusts and chemicals and are at high risk
      of developing CBD and other lung diseases. Our findings emphasize the need for
      awareness of the medical community to detect occupation related diseases in this
      profession.

PMID- 18038922
TI  - Pulmonary arterial hypertension in ANCA-associated vasculitis.
AB  - BACKGROUND AND AIM OF THE WORK: Pulmonary arterial hypertension (PAH) is a severe
      condition characterized by chronic obstruction of small pulmonary arteries
      leading to progressive right heart failure and ultimately death. Inflammatory
      mechanisms may play an important part in the origin or progression of the disease
      in a subset of patients. Whereas PAH is well known complication of some
      connective tissue diseases, it is a rare condition associated with systemic
      vasculitis. In the present report, we describe 4 cases of anti-neutrophil
      cytoplasmic antibodies (ANCA)-related systemic vasculitis (3 with Wegener's
      granulomatosis and 1 with microscopic polyangiitis) associated with PAH. METHODS:
      We describe the clinical features of both ANCA-associated systemic vasculitis and
      PAH. RESULTS: PAH was diagnosed after the onset of the systemic vasculitis in 3
      cases. In 1 case, the systemic vasculitis was active at the diagnosis of PAH and
      treatment of the vasculitis led to a significant improvement of PAH. In the 2
      other patients, PAH occurred while the vasculitis was inactive. The remaining
      patient, for whom Wegener's granulomatosis was diagnosed 2 years after PAH was
      documented, died because of a vasculitis treatment-related side effect.
      CONCLUSIONS: Systemic vasculitides have to be added to the conditions associated
      with PAH. The underlying pathophysiological mechanisms of this association have
      still to be firmly established. It is probable that some PAH are due, at least in
      part, to direct pulmonary arteries involvement by the vasculitic process.

PMID- 18038923
TI  - Thrombocytopenia in sarcoidosis.
AB  - BACKGROUND: Haematological manifestations in sarcoidosis are uncommon. The
      prevalence of thrombocytopenia in sarcoidosis is not well assessed. AIM: To
      describe the main characteristics and outcome of sarcoidosis associated with
      thrombocytopenia. METHODS: We described 2 personal cases and a complete record of
      all reports of thrombocytopenia in sarcoidosis was persuaded through a medline
      multi language computer search from 1972 until now. RESULTS:  CASES REPORTS: In
      the first observation the clinical course was similar to immune thrombocytopenic
      purpura. Steroids were efficient. In the second, we have reported the first used
      of Rituximab in thrombocytopenia in sarcoidosis with a partial success. REVIEW OF
      THE LITERATURE: We identified three main physiopathological mechanisms among the
      31 cases collected. Hypersplenism or splenomegaly was found in ten cases,
      granulomas in bone marrow were found in only four. Auto-immune thrombocytopenic
      purpura was suspected in the other cases. 23 patients had been treated with
      steroids, which proved effective in 21 cases (in association with intravenous
      immunoglobulin(IV-ig) or anti-D. Among the five cases for which steroids were non
      efficient, subsequent splenectomy allowed normalization of platelets count.
      Splenectomy was performed in seven cases, as a first intention treatment for five
      patients, and successful in four. One patient died of massive haemorrhage during
      the surgery. Among the 5 patients treated with IV-Ig, 4 had a complete response.
      CONCLUSION: Different physiopathological mechanisms are responsible of
      thrombocytopenia in sarcoidosis. Granulomas in bone marrow or hypersplenism may
      be involved. Immune thrombocytopenic purpura must be suspected in all other
      cases. Steroids remain the most effective treatment, and must be proposed in
      first intention.

PMID- 18038924
TI  - Alveolar hemorrhage in a patient with sarcoidosis.

PMID- 18038925
TI  - Cardiac performance in the prognosis of interstitial lung diseases.

PMID- 18038926
TI  - Growth characteristics of the Ross 708 broiler chicken.
AB  - A growth trial was conducted with the Ross 708 broiler chicken to corroborate the
      relationships between changes in the growth curve (7 to 35 days) and in vitro
      metabolic parameters. These in vitro parameters also included estimates of the
      expression of certain genes regulating proteins implicated with regulation of
      lipogenesis. Birds were fed diets containing 24% protein from 0 to 14 days of
      age, 21% from 14 to 26 days of age and 18% protein until 35 days of age. Birds
      were selected and killed at ages corresponding to protein changes. Dual X-ray
      absorptiometry (DXA) was used to approximate body composition of birds at day 35.
      The switch from the starter protein level of 24% crude protein to the only
      slightly lower protein grower diet (21% crude protein) increased both in vitro
      lipogenesis and malic enzyme activity. A similar observation was noted when the
      birds were switched to the 18% crude protein finisher diet. These same switches
      also elicited initial increases in malic enzyme, fatty acids synthase and acetyl
      CoA carboxylase gene expression that were not sustained following adaptation to
      the dietary change. Data also show that DXA can be used to estimate body
      composition of this type of bird.

PMID- 18038927
TI  - Modeling the effects of prenatal exposure to aspirin on the postnatal development
      of rat brain.
AB  - Three growth models were used to examine the effects of prenatal exposure to
      aspirin on the postnatal development of brain parts. A total of 60 pregnant rats
      which were divided into three experimental groups and a control group were
      exposed to aspirin doses of 12.5, 25, 37.5 mg/kg, and distilled water,
      respectively. The brain parts of 200 rat pups starting from the first week after
      birth until the fifth week were weighted and the length and width of the cerebrum
      and cerebellum were measured to determine the parameters of the growth models.
      The results indicated that the three models successfully predicted the growth of
      the different brain parts and that aspirin decreased the total brain weight,
      cerebrum length and width, and decreased the cerebellum length and width at
      aspirin dose of 37.5 mg/kg. Further analysis is needed to investigate if aspirin
      effects were carried out through its role in inhibiting prostaglandin production
      and consequently affecting the activity of the hypothalamus-pituitary axis.

PMID- 18038929
TI  - The busy season.

PMID- 18038928
TI  - In vivo evaluation of changes in body composition of transgenic mice expressing
      the myostatin pro domain using dual energy X-ray absorptiometry.
AB  - Over expression of the pro domain of myostatin (MLC-pro) interferes with
      myostatin function, thus promoting muscle growth. The purpose of this study was
      to use dual energy X-ray absorptiometry (DXA) to monitor, in vivo, the course of
      changes in body composition of control and MLC-pro transgenic (TG) mice between
      10 and 91 days of age. MLC-pro TG (n = 32) and littermate control (n = 28) mice
      were produced by mating G-3 male TG mice with non-TG females. At days 10, 20 and
      weekly thereafter to day 62, and finally at day 91, the mice were anesthetized
      and scanned by DXA. By day 34, the body weight of the male TG mice was more than
      that of the control mice and was accompanied by a larger lean mass (LM) and a
      lower percentage of fat (%F) (P < 0.05). At day 91, the male TG mice had 15.6%
      greater body weight, 19.4% more LM, 22.4% lower %F, 11.5% more bone mineral, and
      4.4% higher bone density (P < 0.05). The lower %F in the TG mice was due mainly
      to an increase in LM, rather than reduced FM. Measurements of the TG female mice
      were not different (P > 0.05) from those of control female mice. A region-of
      interest analysis was used to provide a separate measure of the hind limb. By
      using DXA, this study determined the onset and degree of differences in body
      composition of MLC-pro TG and littermate control mice.

PMID- 18038930
TI  - Fighting lies on a patient's Internet blog.

PMID- 18038931
TI  - Threatening words and veiled threats.

PMID- 18038932
TI  - Hey, new dentists: say "yes" to Michigan!

PMID- 18038933
TI  - More hot tips for effective time management.

PMID- 18038934
TI  - How can you give back to the community?

PMID- 18038935
TI  - Make it your association!

PMID- 18038936
TI  - MDA membership: stick with it!

PMID- 18038937
TI  - The MDA at a glance.

PMID- 18038938
TI  - Peer review: a premier member benefit.

PMID- 18038939
TI  - Compensation tactics to attract and keep the best staff.

PMID- 18038940
TI  - Probiotic and prebiotic influence beyond the intestinal tract.
AB  - Probiotics and prebiotics have long been appreciated for their positive
      influences on gut health. Research on the mechanisms and effects of these agents
      shows that their impact reaches beyond the intestine. Effects on the microecology
      and pathology of the oral cavity, stomach, and vaginal tract have been observed.
      Likely mediated through immune influences, systemic effects such as reduced
      severity of colds or other respiratory conditions, impact on allergy incidence
      and symptoms, and reduced absences from work or daycare have also been noted.
      These observations, among others, suggest a broader spectrum of influence than
      commonly considered for these unique substances.

PMID- 18038941
TI  - Cranberries (Vaccinium macrocarpon) and cardiovascular disease risk factors.
AB  - The American cranberry (Vaccinium macrocarpon) is one of the three commercially
      important fruits native to North America. Cranberries are a particularly rich
      source of phenolic phytochemicals, including phenolic acids (benzoic,
      hydroxycinnamic, and ellagic acids) and flavonoids (anthocyanins, flavonols, and
      flavan-3-ols). A growing body of evidence suggests that polyphenols, including
      those found in cranberries, may contribute to reducing the risk of cardiovascular
      disease (CVD) by increasing the resistance of LDL to oxidation, inhibiting
      platelet aggregation, reducing blood pressure, and via other anti-thrombotic and
      anti-inflammatory mechanisms. Research regarding the bioactivity of cranberries
      and their constituents on risk factors for CVD is reviewed.

PMID- 18038942
TI  - Editor's comment. The science and policy feature of this issue.

PMID- 18038943
TI  - Folic acid fortification and supplementation--good for some but not so good for
      others.
AB  - Evidence has established the protective effect of folic acid (FA) fortification
      and periconceptional supplementation on neural tube defects (NTDs). Folic acid
      fortification and periconceptional supplementation of women may reduce the risk
      of certain childhood cancers in their offspring. However, recent human studies
      have suggested that FA supplementation and fortification may promote the
      progression of already existing, undiagnosed, preneoplastic and neoplastic
      lesions, thereby corroborating earlier observations from animal and in vitro
      studies. Following the success of mandatory FA fortification on the reduction of
      NTD rates in the United States and Canada, several countries are currently
      considering whether or not, and at what dose, to institute FA fortification.
      Future debates and decisions regarding FA fortification should take into
      consideration all potential adverse effects and dose-responses of such a measure
      because it may be associated with very serious consequences for many generations.
      In addition to careful monitoring of adverse effects, preclinical and population
      based studied are warranted in order to determine the efficacy, safety, and
      potential deleterious effects of FA fortification and supplementation on cancer
      risk and other health outcomes.

PMID- 18038944
TI  - Food fortification with folic acid: has the other shoe dropped?
AB  - Folic acid (FA) supplementation effectively reduces the rates of children born
      with neural tube defects (NTDs). Currently, 42 nations practice mandatory FA
      fortification to combat NTD. In addition to NTD, FA fortification may also have
      salutary effects on the incidence of orofacial cleft birth defects and have
      secondary benefits in reducing serum homocysteine concentrations and stroke
      mortality. However, a recent note of caution has been raised concerning a
      possible negative effect of mandatory FA fortification on the incidence of
      colorectal cancer.

PMID- 18038945
TI  - Parallel and serial search in haptics.
AB  - We propose a model that distinguishes between parallel and serial search in
      haptics. To test this model, participants performed three haptic search
      experiments in which a target and distractors were presented to their fingertips.
      The participants indicated a target's presence by lifting the corresponding
      finger, or its absence by lifting all fingers. In one experiment, the target was
      a cross and the distractors were circles. In another, the target was a vertical
      line and the distractors were horizontal lines. In both cases, we found a serial
      search pattern. In a final experiment, the target was a horizontal line and the
      distractors were surfaces without any contours. In this case, we found a parallel
      search pattern. We conclude that the model can describe our data very well.

PMID- 18038946
TI  - Similarity structure in visual speech perception and optical phonetic signals.
AB  - A complete understanding of visual phonetic perception (lipreading) requires
      linking perceptual effects to physical stimulus properties. However, the talking
      face is a highly complex stimulus, affording innumerable possible physical
      measurements. In the search for isomorphism between stimulus properties and
      phoneticeffects, second-order isomorphism was examined between theperceptual
      similarities of video-recorded perceptually identified speech syllables and the
      physical similarities among the stimuli. Four talkers produced the stimulus
      syllables comprising 23 initial consonants followed by one of three vowels. Six
      normal-hearing participants identified the syllables in a visual-only condition.
      Perceptual stimulus dissimilarity was quantified using the Euclidean distances
      between stimuli in perceptual spaces obtained via multidimensional scaling.
      Physical stimulus dissimilarity was quantified using face points recorded in
      three dimensions by an optical motion capture system. The variance accounted for
      in the relationship between the perceptual and the physical dissimilarities was
      evaluated using both the raw dissimilarities and the weighted dissimilarities.
      With weighting and the full set of 3-D optical data, the variance accounted for
      ranged between 46% and 66% across talkers and between 49% and 64% across vowels.
      The robust second-order relationship between the sparse 3-D point representation
      of visible speech and the perceptual effects suggests that the 3-D point
      representation is a viable basis for controlled studies of first-order
      relationships between visual phonetic perception and physical stimulus
      attributes.

PMID- 18038947
TI  - Harmonic expectation and affect in Western music: effects of attention and
      training.
AB  - We investigated the effects of selective attention and musical training on the
      processing ofharmonic expectations. In Experiment 1, participants with and
      without musical training were required to respond to the contour of melodies as
      they were presented with chord progressions that were highly expected, slightly
      unexpected, or extremely unexpected. Reaction time and accuracy results showed
      that when attention was focused on the melody, musically trained participants
      were still sensitive to different harmonic expectations, whereas participants
      with no musical training were undifferentiated across expectation conditions. In
      Experiment 2, participants were required to listen holistically to the entire
      chord progression and to rate their preference for each chord progression.
      Results from preference ratings showed that all the participants, with or without
      musical training, were sensitive to manipulations of harmonic expectations.
      Experiments 3 and 4 showed that changing the speed of presentation of chord
      progressions did not affect the pattern of results. The four experiments together
      highlight the importance of attentional focus in musical training, especially as
      it relates to the processing of harmonic expectations.

PMID- 18038948
TI  - Attentional mechanisms in visual signal detection: the effects of simultaneous
      and delayed noise and pattern masks.
AB  - The attentional cuing effects in detection and some discrimination tasks depend
      on the use of backward masks and on the presence of external noise in the
      display. These effects have been attributed to an interruption masking mechanism,
      which terminates stimulus processing prematurely, and an external noise exclusion
      mechanism, which minimizes the perceptual effects of noise. To test whether the
      dependencies on masking and external noise are expressions of a single mechanism,
      observers detected grating patch stimuli, masked with noise masks or pattern
      masks, presented either simultaneously or after a delay of 60-90 msec. Contrary
      to an external noise exclusion account, but consistent with an interruption
      masking account, cuing effects were largest when the masks were delayed. However,
      weaker cuing effects were obtained with simultaneous masks, contrary to an
      interruption masking account. These results suggest that attentional effects in
      simple visual judgments are affected by mechanisms of both kinds.

PMID- 18038949
TI  - What influences visual search efficiency? Disentangling contributions of
      preattentive and postattentive processes.
AB  - The present experiments introduce a new search technique for disentangling
      contributions of preattentive guidance and postattentive template matching to
      search efficiency. Participants performed searches (for negative or positive
      faces in Experiment 1; pop-out search in Experiment 2; conjunction search in
      Experiment 3) under either standard viewing conditions or a new restricted
      viewing condition in which items were occluded by black placeholders and revealed
      only when a participant moved the mouse pointer over the black square. Under full
      viewing conditions, search performance can be aided by both preattentive and
      postattentive mechanisms, whereas the mouse-contingent search relies solely on
      postattentive template-matching processes. Results demonstrate the utility of
      this new methodology for distinguishing contributions of preattentive guidance
      and postattentive template-matching processes in ambiguous search situations.
      Furthermore, application of the new restricting viewing method to search for
      emotionally expressive faces suggested that emotional information is processed
      preattentively and influences the allocation of focal attention.

PMID- 18038950
TI  - Impact of contingency manipulations on accessory stimulus effects.
AB  - Accessory tone stimuli facilitate response performance despite being irrelevant
      for the current task. In order to investigate which processes are affected by
      accessory stimuli, we presented accessory tones in a simple response time (RT)
      task while varying the contingencies between accessory stimulation and either
      responses(Experiment 1) or stimulus conditions (Experiment 2). Accessory tones
      speeded up responding to a larger degree when they were conjointly presented
      within go compared with no-go trials. In contrast, contingency variation with
      stimulus conditions did not alter the impact of accessory stimuli. Additionally,
      accessory tones increased response force. Thus, we conclude that in simple RT
      tasks accessory tones influence response-related stages such as response
      selection and response execution rather than perceptual processes.

PMID- 18038951
TI  - Natural scene categorization with minimal attention: evidence from negative
      priming.
AB  - Research has demonstrated that objects in natural scenes are categorized without
      the deployment of attention. However, in these types of studies, participants
      were required to directly respond to peripherally presented scenes, which might
      lead some participants to move their attention. If this is the case, the above
      conclusion concerning natural scenes may not be valid. We investigated this issue
      by using a negative priming (NP) paradigm in which participants did not directly
      respond to peripheral stimuli. Our results showed NP effect from ignored stimuli
      in natural scene categorization, but neither in letter discrimination (Experiment
      1) nor in line-drawing categorization (Experiment 2). In addition, NP effects
      were observed even when probe stimuli were words (Experiments 3A and 3B). These
      findings suggest that people can categorize objects in natural scenes with
      minimal attention, that this process is specific to natural scenes, and that it
      is based on the semantic information of the images.

PMID- 18038952
TI  - The effect of amplitude modulation on intelligibility of time-varying sinusoidal
      speech in children and adults.
AB  - Although researchers are currently studying auditory object formation in adults,
      little is known about the development of this phenomenon in children. Amplitude
      modulation has been suggested as one of the characteristics of the speech signal
      that allows auditory grouping. In this experiment, we evaluated children (4 to 13
      years of age) and adults to examine whether children's ability to use amplitude
      modulation (AM) in perception of time-varying sinusoidal (TVS) sentences is
      different from that of adults, and whether there are developmental changes. We
      evaluated performance on recognition of TVS sentences (unmodulated, amplitude
      comodulated at 25, 50, 100, and 200 Hz, and amplitude-modulated using conflicting
      frequencies). Overall, the youngest children performed more poorly than did older
      children and adults. However, difference scores, defined as the percentage of
      phonemes correct in a given modulation condition minus the percentage correct for
      the unmodulated condition, showed no significant effects of age. Unlike the
      findings of previous studies (Carrell & Opie, 1992), these results support the
      ability of modulation with conflicting frequencies to improve intelligibility.
      The present study provides evidence that children and adults receive the same
      benefits (or decrements) from amplitude modulation.

PMID- 18038953
TI  - Stimulus and response priming in rapid serial visual presentation: evidence for a
      dissociation.
AB  - Two experiments investigated the capacity demands of stimulus and response
      priming in a rapid serial visual presentation (RSVP) task. Three targets were
      presented in a stream of visual symbols: The first two (T1 and T2) required an
      unspeeded manual response at the end of the trial, but the third (T3) called for
      an immediate,speeded manual response. T2 and T3 either were identical (fully
      compatible), required the same response (response compatible), or required
      different responses (incompatible). Priming in the fully compatible condition
      depended strongly on successful identification of the priming stimulus, whereas
      response-based priming was observed regardless of whether the prime could be
      reported or not. These findings suggest that stimulus coding and response coding
      are automatic processes, unaffected by attentional capacity constraints, followed
      by capacity-limited stimulus consolidation and response selection. Moreover, even
      though response codes are activated automatically upon stimulus processing, both
      types of codes act, and affect behavior, independently.

PMID- 18038954
TI  - Ignorance is bliss: the role of observer expectation in dynamic spatial tuning of
      the attentional focus.
AB  - When two sequential targets (T1, T2) are inserted in an RSVP stream of
      distractors, perception of T2 is impaired at intertarget lags shorter than 700
      msec. Paradoxically, this deficit disappears when T2 is presented directly after
      T1 (lag-1 sparing). Visser, Bischof, and Di Lollo (1999) found that lag-1 sparing
      occurs only when T1 and T2 are presented in the same stream. In contrast, Shih
      (2000) obtained lag-1 sparing with targets insepa-rate streams. Four experiments
      addressed this inconsistency and revealed lag-1 sparing with targets in different
      streams, but only when observers had no foreknowledge of T1's location. We
      hypothesized that when T1 location is known, attention is focused narrowly on
      that stream; if T2 then appears in the other stream it is missed, and lag-1
      sparing does not occur. When T1 location is not known, attention is focused
      broadly, encompassing both streams, and lag-1 sparing ensues.

PMID- 18038955
TI  - Hits and false positives in face matching: a familiarity-based dissociation.
AB  - In recognition memory for unfamiliar faces, performance for target-present items
      (hits) does not correlate with performance for target-absent items (false
      positives), a result which runs counter to the more usual mirror effect. In this
      paper we examinesubjects' performance on fac e matching, a nd demonstrate no
      relationship-between performance on matching items and performance on nonmatching
      items. This absence of a mirror effect occurs for multidistractor, 1-in-10
      matching tasks (Experiment 1) and for simple paired-item tasks (Experiment 2). In
      Experiment 3 we demonstrate that matching familiar faces produces a strong mirror
      effect. However, inverting the familiar faces causes the association to disappear
      once more (Experiment 4). We argue thatfamiliar and unfamiliar faces are
      represented in qualitatively different ways.

PMID- 18038956
TI  - Nonverbal arithmetic in humans: light from noise.
AB  - Animal and human data suggest the existence of a cross-species system of analog
      number representation (e.g., Cordes, Gelman, Gallistel, & Whalen, 2001; Meeck &
      Church, 1983), which may mediate the computation of statistical regularities in
      the environment (Gallistel, Gelman, & Cordes, 2006). However, evidence of
      arithmetic manipulation of these nonverbal magnitude representations is sparse
      and lacking in depth. This study uses the analysis of variability as a tool for
      understanding properties of these combinatorial processes. Human subjects
      participated in tasks requiring responses dependent upon the addition,
      subtraction, or reproduction of nonverbal counts. Variance analyses revealed that
      the magnitude of both inputs and answer contributed to the variability in the
      arithmetic responses, with operand variability dominating. Other contributing
      factors to the observed variability and implications for logarithmic versus
      scalar models of magnitude representation are discussed in light of these
      results.

PMID- 18038957
TI  - In sight, out of mind: the role of eye movements in the rapid resumption of
      visual search.
AB  - Three experiments investigated the role of eye movements in the rapid resumption
      of an interrupted search. Passive monitoring of eye position in Experiment 1
      showed that rapid resumption was associated with a short distance between the eye
      and the target on the next-to-last look before target detection. Experiments 2
      and 3 used two different methods for presenting the target to the point of eye
      fixation on some trials. If eye position alone is predictive, rapid resumption
      should increase when the target is near fixation. The results showed that gaze
      contingent targets increased overall search success, but that the proportion of
      rapid responses decreased dramatically. We conclude that rather than depending on
      a high-quality single look at a search target, rapid resumption of search depends
      on two glances; a first glance in which a hypothesis is formed, and a second
      glance in which the hypothesis is confirmed.

PMID- 18038958
TI  - Dividing attention between two different categories and locations in rapid serial
      visual presentations.
AB  - When two targets are embedded in a rapid serial visual presentation (RSVP) stream
      of distractors, perception of the second target is impaired if the intertarget
      lag is relatively short (less than 500 msec). This phenomenon, called attentional
      blink, has been attributed to a temporal inability of attentional resources.
      Nevertheless, a recent study found that observers could monitor two RSVP streams
      concurrently for up to four items presented in close succession, suggesting a
      much larger visual capacity limit. However, such high-capacity performance could
      be obtained by a rapid shift of attention, rather than concurrent monitoring of
      multiple locations. Therefore, the present study examined these alternatives.
      Results from six experiments indicate that observers can concurrently monitor two
      noncontiguous locations, even when targets and distractors are from different
      categories, such as digits, English alphabet letters, Japanese characters, and
      pseudocharacters. These results can be explained in terms of a modified input
      filtering model in which a multidimensional attentional set can be flexibly
      configured at different spatial locations.

PMID- 18038959
TI  - The absence of an auditory-visual attentional blink is not due to echoic memory.
AB  - The second of two targets is often missed when presented shortly after the first
      target--a phenomenon referred to as the attentional blink (AB). Whereas the AB is
      a robust phenomenon within sensory modalities, the evidence for cross-modal ABs
      is rather mixed. Here, we test the possibility that the absence of an auditory
      visual AB for visual letter recognition when streams of tones are used is due to
      the efficient use of echoic memory, allowing for the postponement of auditory
      processing. However, forcing participants to immediately process the auditory
      target, either by presenting interfering sounds during retrieval or by making the
      first target directly relevant for a speeded response to the second target, did
      not result in a return of a cross-modal AB. Thefindings argue against echoic
      memory as an explanation for efficient cross-modal processing. Instead, we
      hypothesized that a cross-modal AB may be observed when the different modalities
      use common representations, such as semantic representations. In support of this,
      a deficit for visual letter recognition returned when the auditory task required
      a distinction between spoken digits and letters.

PMID- 18038960
TI  - Preparation for horizontal or vertical dimensions affects the right-left
      prevalence effect.
AB  - When stimulus and response simultaneously vary in both horizontal and vertical
      dimensions, the stimulus-response compatibility effect is often larger for the
      horizontal dimension. We investigated the role of preparation for each dimension
      in this right-left prevalence. In Experiment 1, tasks based on horizontal and
      vertical dimensions were mixed in random order, and the relevant dimension in
      each trial was cued with a variable cue-target stimulus onset asynchrony (SOA). A
      right-left prevalence effect was observed only when participants prepared for the
      upcoming task. Experiment 2 replicated the absence of the prevalence effect for
      the simultaneous presentation of cue and target using a fixed SOA of 0 msec. In
      Experiment 3, the right-left prevalence emerged with a 0-msec SOA when
      participants prepared for e achdimension basedon its frequency. These
      resultssuggest that participants' internal set can be greater for the horizontal
      dimension, leading to the right-left prevalence effect.

PMID- 18038961
TI  - The concavity effect is a compound of local and global effects.
AB  - Using a change detection paradigm, Barenholtz, Cohen, Feldman, and Singh (2003)
      found that changes in concave regions of a contour are more easily detected than
      changes in convex regions. In a series of three experiments, we investigated this
      concavity effect using the same paradigm. We observed the effect in wire-like
      stimuli as well as in silhouettes (Experiment 1) and in complex, smoothed images
      as opposed to angular polygons (Experiment 2). We also observed a systematic
      effect of the magnitude of the change (Experiment 1). Furthermore, we find that
      the effect cannot be attributed to either local or global processing effects, but
      rather to a combination of both "mere" concaveness and an effect due to changes
      in the perceived part structure of the stimulus object (Experiment 3). For our
      data analysis, we used a nonparametric bootstrap method, which greatly increases
      sensitivity (compared to more traditional analyses like ANOVA).

PMID- 18038962
TI  - The perception of scatterplots.
AB  - Four experiments investigated the perception of correlations from scatterplots.
      All graphic properties, other than error variance, that have been shown to affect
      subjective but not objective correlation (r) were held constant. Participants in
      Experiment 1 ranked 21 scatterplots according to the magnitude of r. In
      Experiments 2 and 3, participants made yes/no judgments to indicate whether a
      scatterplot was high (signal) or low (noise). Values of r for signal and noise
      scatterplots varied across participants. Differences between correlations for
      signal and for noise scatterplots were constant in r in Experiment 2, and
      constant in r2 in Experiment 3. Standard deviations of the ranks in Experiment 1
      and d' values in Experiments 2 and 3 showed that discriminability increased with
      the magnitude of r. In Experiment 4, faculty and graduate students in psychology
      and sociology made point estimates of r for single scatterplots. Estimates were
      negatively accelerated functions of objective correlation.

PMID- 18038963
TI  - Polyisoprenylated benzoylphloroglucinol derivatives from Hypericum sampsonii.
AB  - Bioassay-directed fractionation using multidrug-resistant (MDR) Staphylococcus
      aureus resulted in the isolation of four new polyprenylated benzophloroglucinol
      derivatives, sampsoniones N-Q (1-4), and four known compounds, 7-epiclusianone
      (5) and sampsoniones B, L, and R, from the roots of Hypericum sampsonii. The
      structures of these compounds were established by analysis of spectroscopic data,
      and the structures of 4 and 5 were determined by single-crystal X-ray diffraction
      crystallography. In the bioassay, 7-epiclusianone (5) showed promising activity
      with a minimum inhibitory concentration (MIC) of 7.3 microM against the NorA
      overexpressing MDR S. aureus strain SA-1199B; the positive control antibiotic
      norfloxacin showed activity at MIC 100 microM.

PMID- 18038964
TI  - Fluorometric identification of 5-methylcytosine modification in DNA: combination
      of photosensitized oxidation and invasive cleavage.
AB  - An efficient fluorometric detection system of DNA methylation has been developed
      by a combination of a photooxidative DNA cleavage reaction with 2-methyl-1,4
      naphthoquinone (NQ) chromophore and an invasive cleavage reaction with human Flap
      endonuclease-1. Enzymatic treatment of a mixture of photochemically fragmented
      target oligodeoxynucleotides (ODNs) at 5-methylcytosine mC) and hairpin-like
      probe oligomer possessing a fluorophore (F) and a quencher (D) resulted in a
      dramatic enhancement of fluorescence. In contrast, fluorescence emission for the
      ODN containing cytosine but not mC at the target sequence was extremely weak. In
      addition, by monitoring the fluorescence change, this system allows for the
      detection of mC in DNA at subfemtomole amounts. This system would provide a
      highly sensitive protocol for determining the methylation status in DNA by
      fluorescence emission.

PMID- 18038965
TI  - Novel near-infrared fluorescent integrin-targeted DFO analogue.
AB  - Desferrioxamine (DFO), a siderophore initially isolated from Streptomyces
      pilosus, possesses extraordinary metal binding properties with wide biomedical
      applications that include chelation therapy, nuclear imaging, and
      antiproliferation. In this work, we prepared a novel multifunctional agent
      consisting of (i) a near-infrared (NIR) fluorescent probe-cypate; (ii) an
      integrin alpha vbeta3 receptor (ABIR)-avid cyclic RGD peptide, and (iii) a DFO
      moiety, DFO-cypate-cyclo[RGDfK(approximately)] (1, with approximately
      representing the cypate conjugation site at the side chain of lysine; f is d
      phenylalanine). Compound 1 and two control compounds, cypate
      cyclo[RGDfK(approximately)] ( 2) and cypate-DFO ( 3), were synthesized by modular
      assembly of the corresponding protected RGD peptide cyclo[R(Pbf)GD(OBut)fK] and
      DFO on the dicarboxylic acid-containing cypate scaffold in solution. The three
      compounds exhibited similar UV-vis and emission spectral properties. Metal
      binding analysis shows that DFO as well as 1 and 3 exhibited relatively high
      binding affinity with Fe(III), Al(III), and Ga(III). In contrast to Ga(III), the
      binding of Fe to 1 and 3 quenched the fluorescence emission of cypate
      significantly, suggesting an efficient metal-mediated approach to perturb the
      spectral properties of NIR fluorescent carbocyanine probes. In vitro, 1 showed a
      high ABIR binding affinity (10 (-7) M) comparable to that of 2 and the reference
      peptide cyclo(RGDfV), indicating that both DFO and cypate motifs did not
      interfere significantly with the molecular recognition of the cyclic RGD motif
      with ABIR. Fluorescence microscopy showed that internalization of 1 and 2 in ABIR
      positive A549 cells at 1 h postincubation was higher than 3 and cypate alone,
      demonstrating that incorporating ABIR-targeting RGD motif could improve cellular
      internalization of DFO analogues. The ensemble of these findings demonstrate the
      use of multifunctional NIR fluorescent ABIR-targeting DFO analogues to modulate
      the spectral properties of the NIR fluorescent probe by the chelating properties
      of DFO and visualize intracellular delivery of DFO by receptor-specific peptides.
      These features provide a strategy to explore the potential of 1 in tumor imaging
      and treatment as well as some molecular recognition processes mediated by metal
      ions.

PMID- 18038966
TI  - Novel, orally effective cyanide antidotes.
AB  - A series of prodrugs of 3-mercaptopyruvate (3-MP), the substrate for the enzyme 3
      mercaptopyruvate/cyanide sulfurtransferase (3-MPST) that converts cyanide to the
      nontoxic thiocyanate, which are highly effective cyanide antidotes, have been
      developed. These prodrugs of 3-MP are unique in being not only orally
      bioavailable, but may be administered up to an hour prior to cyanide as a
      prophylactic agent and are both rapid- or slow-acting when given parenterally.

PMID- 18038967
TI  - Cannabilactones: a novel class of CB2 selective agonists with peripheral
      analgesic activity.
AB  - The identification of the CB2 cannabinoid receptor has provided a novel target
      for the development of therapeutically useful cannabinergic molecules. We have
      synthesized benzo[ c]chromen-6-one analogs possessing high affinity and
      selectivity for this receptor. These novel compounds are structurally related to
      cannabinol (6,6,9-trimethyl-3-pentyl-6 H-benzo[ c]chromen-1-ol), a natural
      constituent of cannabis with modest CB2 selectivity. Key pharmacophoric features
      of the new selective agonists include a 3-(1',1'-dimethylheptyl) side chain and a
      6-oxo group on the cannabinoid tricyclic structure that characterizes this class
      of compounds as "cannabilactones." Our results suggest that the six-membered
      lactone pharmacophore is critical for CB2 receptor selectivity. Optimal receptor
      subtype selectivity of 490-fold and subnanomolar affinity for the CB2 receptor is
      exhibited by a 9-hydroxyl analog 5 (AM1714), while the 9-methoxy analog 4b
      (AM1710) had a 54-fold CB2 selectivity. X-ray crystallography and molecular
      modeling show the cannabilactones to have a planar ring conformation. In vitro
      testing revealed that the novel compounds are CB2 agonists, while in vivo testing
      of cannabilactones 4b and 5 found them to possess potent peripheral analgesic
      activity.

PMID- 18038968
TI  - (S)-N-{3-[1-cyclopropyl-1-(2,4-difluoro-phenyl)-ethyl]-1H-indol-7-yl}
      methanesulfonamide: a potent, nonsteroidal, functional antagonist of the
      mineralocorticoid receptor.
AB  - A novel, potent series of indole analogs were recently developed as MR
      antagonists, culminating in 14. This compound represents the first MR antagonist
      in this class of molecules, exhibiting picomolar binding affinity and in vivo
      blood pressure lowering at pharmaceutically relevant doses.

PMID- 18038969
TI  - Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases
      for cancer treatment.
AB  - Mycophenolic acid (MPA), an inhibitor of IMP-dehydrogenase (IMPDH), is used
      worldwide in transplantation. Recently, numerous studies showed its importance in
      cancer treatment. Consequently, MPA entered clinical trials in advanced multiple
      myeloma patients. Suberoylanilide hydroxamic acid (SAHA), a potent
      differentiation agent acting through inhibition of histone deacetylases (HDACs),
      was recently approved for treatment of cutaneous T cell lymphoma. We report
      herein the synthesis of dual inhibitors of IMPDH and HDACs. We found that
      mycophenolic hydroxamic acid (9, MAHA) inhibits both IMPDH (Ki=30 nM) and HDAC
      (IC50=5.0 microM). A modification of SAHA with groups known to interact with
      IMPDH afforded a SAHA analogue 14, which inhibits IMPDH (Ki=1.7 microM) and HDAC
      (IC50=0.06 microM). Both MAHA (IC50=4.8 microM) and SAHA analogue 14 (IC50=7.7
      microM) were more potent than parent compounds as antiproliferation agents. They
      were also significantly more potent as differentiation inducers.

PMID- 18038970
TI  - Nonsteroidal glucocorticoid agonists: tetrahydronaphthalenes with alternative
      steroidal A-ring mimetics possessing dissociated
      (transrepression/transactivation) efficacy selectivity.
AB  - The synthesis and biological activity of tetrahydronaphthalene derivatives
      coupled to various heterocycles are described. These compounds are potent
      glucocorticoid receptor agonists with efficacy selectivity in an NFkappaB
      glucocorticoid receptor (GR) agonist assay (representing transrepression effects)
      over an MMTV GR agonist assay (representing transactivation effects). Quinolones,
      indoles, and C- and N-linked quinolines are some of the heterocycles that provide
      efficacy selectivity. For example, the isoquinoline 49D1E2 has NFkappaB agonism
      with pIC50 of 8.66 (89%) and reduced efficacy in MMTV agonism (6%), and the
      quinoline 55D1E1 has NFkappaB agonism with pIC50 of 9.30 (101%) and reduced
      efficacy in MMTV agonism with pEC50 of 8.02 (47%). A description of how a
      compound from each class is modeled in the active site of the receptor is given.

PMID- 18038971
TI  - Nuclear magnetic resonance fragment-based identification of novel FKBP12
      inhibitors.
AB  - Peptidyl-prolyl cis-trans isomerases are a group of cytosolic enzymes initially
      characterized by their ability to catalyze the cis-trans isomerization of
      peptidyl-prolyl bonds. This represents a significant event for protein folding
      because cis-proline introduces critical bends within the protein conformation.
      FK506-binding proteins (FKBPs) represent one of the three families of enzymes
      sharing peptidyl-prolyl cis-trans isomerase activity. Inhibitors of FKBP12, in
      particular, have potent neurotrophic properties both in vivo and in vitro. Here,
      we describe a fragment-based unbiased nuclear magnetic resonance drug discovery
      approach for the identification of novel classes of chemical inhibitors against
      FKBP12. Compared to FK506, the fragment-based FKBP12 inhibitors developed herein
      possess significant advantages as drug candidates.

PMID- 18038972
TI  - Isoflavone glycitein diminished plasma cholesterol in female golden Syrian
      hamsters.
AB  - The soybean isoflavones, daidzein, genistein, and glycitein, were hypothesized to
      act as cholesterol-lowering components, separate from soy protein. Pure synthetic
      daidzein, genistein, or glycitein (0.9 mmol/kg diet) or a casein-based control
      diet was fed to groups of 10 female Golden Syrian hamsters for 4 weeks. Hamsters
      fed glycitein had significantly lower plasma total (by 15%) and non-HDL (by 24%)
      cholesterol compared with those fed casein (P<0.05). Daidzein and genistein's
      effects on these lipids did not differ from the effects of either casein or
      glycitein. Plasma HDL cholesterol and triglyceride concentrations were not
      significantly affected by dietary treatments. The percentage of urinary recovery
      of the ingested dose of each isoflavone was glycitein>daidzein>genistein (33.2%,
      4.6%, 2.2%, respectively), with the apparent absorption of glycitein
      significantly greater than that of the other isoflavones. These data suggest that
      glycitein's greater cholesterol-lowering effect was due to its greater
      bioavailability, as reflected in its urinary recovery compared with that of the
      other isoflavones.

PMID- 18038973
TI  - Monovarietal extra virgin olive oils: correlation between thermal properties and
      chemical composition.
AB  - Thermal properties of monovarietal extra virgin olive oils were evaluated by
      means of differential scanning calorimetry (upon cooling) and related to their
      chemical composition (triacylglycerols, diacylglycerols, total and free fatty
      acids, oxidation status). The overall crystallization enthalpy did not
      significantly differ among samples and did not account for the differences
      observed in chemical compositions. On the contrary, a higher degree of
      unsaturation in the lipid profile induced a shift of the crystallization onset
      towards lower temperatures and narrowing of the crystallization temperature
      range. The presence of triacylglycerol lysis and lipid oxidation products shifted
      the crystallization towards higher temperatures and the phase transition
      developed over a larger temperature range. Differential scanning calorimetry
      thermograms were deconvoluted into three constituent exothermic peaks for all
      samples. The area of the two lower-temperature exotherms was found to be
      statistically correlated with the amount of triunsaturated and monosaturated
      triacylglycerols present in the oil. Thermal properties of extra virgin olive oil
      were found to be affected by oil chemical composition.

PMID- 18038974
TI  - Inhibition of low-density lipoprotein oxidation and oxidative burst in
      polymorphonuclear neutrophils by caffeic acid and hispidin derivatives isolated
      from sword brake fern (Pteris ensiformis Burm.).
AB  - Several antioxidant compounds have been previously identified from sword brake
      fern (Pteris ensiformis Burm.) by DPPH bleaching and Trolox equivalent
      antioxidant capacity (TEAC) analyses. Among the isolates, 7-O
      caffeoylhydroxymaltol 3-O-beta-D-glucopyranoside and hispidin 4-O-beta- D
      glucopyranoside [6-(3,4-dihydroxystyryl)-4-O-beta-D-glucopyranoside-2-pyrone]
      were two new compounds. The aim of this study is to elucidate the possible effect
      of the aqueous extract of sword brake fern (SBF) and these two compounds in
      preventing atherosclerosis. The results demonstrated that SBF and these two
      compounds strongly inhibited Cu2+-mediated low-density lipoprotein (LDL)
      oxidation measured by thiobarbituric acid-reactive substances assay (TBARS),
      conjugated diene production, and relative electrophoretic mobility. The
      commercial antioxidant dl-alpha-tocopherol showed lower antioxidant activity than
      these two compounds at the same molecular concentration. SBF and these two
      compounds also suppressed N-formylmethionyl-leucylphenylalanine (fMLP)-stimulated
      reactive oxygen species (ROS) production in human polymorphonuclear neutrophils
      (PMN). These findings indicate that sword brake fern may prevent atherosclerosis
      via inhibition of both LDL oxidation and ROS production.

PMID- 18038975
TI  - Calcium effects on the functionality of a modified whey protein ingredient.
AB  - The primary objective for this study addressed the effects of supplemental
      calcium on the functional properties of a modified whey protein ingredient
      (mWPC), prepared by acidification to pH 3.35, followed by extended heat
      treatment, gelation, and spray drying. In the presence of added calcium (mWPC
      Ca2+), protein solutions showed increased thickening capacity, especially under
      refrigeration temperatures, compared to dispersions made with mWPC alone. A
      rheological assessment included the determination of (i) power law parameters,
      (ii) viscoelastic properties, and (iii) the effects of heating and cooling on
      these protein systems. The sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) banding profile suggested that various disulfide
      linked molecular forms of beta-lactoglobulin, bovine serum albumin, and
      immunoglobulin were likely formed during manufacturing of the mWPC ingredient
      based on the patterns obtained when electrophoresis was performed in the absence
      of beta-mercaptoethanol compared to those observed with commercial WPC samples.
      An enhanced water-holding capacity was measured in mWPC-Ca2+ dispersions.
      Differential scanning calorimetry established that the addition of calcium salts
      caused a 2-fold increase in the amount of bound or unfreezeable water compared to
      mWPC controls. The physical appearance of the network structure varied
      significantly upon visualization with scanning electron microscopy, in which case
      the formation of large, rounded, spherical structures was noted in mWPC-Ca2+
      samples, ascribed to an increased surface tension caused by the higher salt
      content. Ultimately, such attributes may afford distinct advantages for whey
      based ingredients intended for application within food systems, especially under
      cold processing conditions.

PMID- 18038976
TI  - The role of lysine amino nitrogen in the biosynthesis of mousy off-flavor
      compounds by Dekkera anomala.
AB  - Mousy off-flavor is an insidious and economically disastrous microbiologically
      derived spoilage characteristic of wine and other fermented beverages. Tainted
      wines are rendered unpalatable and there is currently no satisfactory procedure
      for removal of the off-flavor. Here we report the confirmation of that both d-
      and l-lysine can act as a precursor for the formation of mousy off-flavor N
      heterocycles. Further, through the use of stable isotope feeding experiments, we
      could establish that a pentylamine group from lysine is incorporated into the
      piperideine moiety of two off-flavor N-heterocycles. A biochemical pathway for
      the formation of mousy off-flavor compounds is proposed.

PMID- 18038977
TI  - Detection of primary and secondary oxidation products by Fourier transform
      infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (NMR) in sunflower
      oil during storage.
AB  - The oxidation of sunflower oil, stored in closed receptacles at room temperature
      for a period of 10 years, was monitored using Fourier transform infrared
      spectroscopy (FTIR) and 1H nuclear magnetic resonance (NMR). The objective was to
      understand the evolution of the oxidation process in sunflower oil under the
      conditions above mentioned. These techniques provide information about the
      oxidative status of several oil samples and the primary and some of the secondary
      oxidation products formed in the oxidation process. The results obtained show
      that, under these conditions, sunflower oxidation takes place in a different way
      to that at higher temperatures with aeration. The 1H NMR spectra show that in the
      first oxidation stages of the process only hydroperoxides supporting cis, trans
      conjugated double bonds are formed and that at more advanced stages
      hydroperoxides having trans, trans-conjugated double bonds are generated, with
      the latter always being in a smaller proportion than the former. In addition, the
      presence of hydroxy derivatives supporting cis, trans-conjugated double bonds
      among the primary oxidation compounds is shown for the first time. Also, from
      early oxidation stages onward and unlike the process at 70 degrees C with
      aeration, it is noticeable that 4-hydroxy- trans-2-alkenals are formed in much
      higher proportions than 4-hydroperoxy- trans-2-alkenals. This fact could be
      associated with the presence of hydroxy derivatives with cis, trans-conjugated
      double bonds among the primary oxidation products and the limited concentration
      of oxygen during the oxidation. Furthermore, relationships between some oxidation
      conditions and the oxidation level of the samples were statistically analyzed.

PMID- 18038978
TI  - Hypolipidemic effects of Citrus bergamia Risso et Poiteau juice in rats fed a
      hypercholesterolemic diet.
AB  - Citrus bergamia Risso et Poiteau fruits have been traditionally utilized, in
      Calabria (Italy), as a popular remedy for their hypolipidemic properties. C.
      bergamia juice total phenol content (2474.35+/-38 microg/mL) was evaluated by the
      Folin-Ciocalteu method; moreover, HPLC analysis led to the identification of
      naringin (520 ppm), neoeriocitrin (370 ppm), and neohesperidin (310 ppm). The
      present study was designed to investigate the hypolipidemic effects of C.
      bergamia juice and its protective effect on liver of hyperlipidemic rats. Chronic
      administration of C. bergamia (1 mL/rat/day) provoked a significant reduction in
      serum cholesterol, triglycerides, and low-density lipoprotein (LDL) levels and an
      increase in high-density lipoprotein (HDL) levels; moreover, histopathological
      observations showed, in rats submitted to C. bergamia treatment, a protection of
      hepatic parenchyma. In addition, fecal neutral sterols and fecal bile acid
      excretion was found to be increased after C. bergamia treatment. These results
      suggest that the hypocholesterolemic effect of C. bergamia may be mediated by the
      increase in fecal neutral sterols and total bile acids excretion. In addition to
      the hypolipidemic effect, the juice shows radical scavenging activity in the
      diphenylpicrylhydrazyl (DPPH) test; probably the two effects are related. These
      observations suggest that the positive intake of C. bergamia may reduce the risk
      of some cardiovascular diseases through its radical scavenging function and
      hypocholesterolemic action.

PMID- 18038979
TI  - Heat-killed cells of lactobacilli skew the immune response toward T helper 1
      polarization in mouse splenocytes and dendritic cell-treated T cells.
AB  - It is believed that probiotics play an important role for the health of the host,
      including modulation of immune responses. Most studies have focused on the
      immunomodulatory effects of viable cells of lactic acid bacteria; however, we
      investigated those of heat-killed cells of lactic acid bacteria in this study. We
      first observed the effects on immune functions via stimulating splenocytes with
      three heat-killed Lactobacillus strains. Furthermore, we also investigated the
      effect of mouse dendritic cells (DCs) treated with these heat-killed
      Lactobacillus strains on T cell responses. The results showed that these
      Lactobacillus strains were able to stimulate cell proliferation and interleukin
      (IL)-10, IL-12 p70, and interferon (IFN)-gamma production but not transforming
      growth factor (TGF)-beta in splenocytes. In addition, these heat-killed
      Lactobacillus strains also stimulated high-level secretion of IL-12 p70 in DCs
      and switched T cells to T helper (Th) 1 immune responses, as evidenced by the
      elevated secretion of IFN-gamma but not IL-5, IL-13, and TGF-beta. These results
      showed that lactobacilli play a potentially important role in modulating immune
      responses and allergic reactions.

PMID- 18038980
TI  - Fatty acid, triacylglycerol, phytosterol, and tocopherol variations in kernel oil
      of Malatya apricots from Turkey.
AB  - The fatty acid, sn-2 fatty acid, triacyglycerol (TAG), tocopherol, and
      phytosterol compositions of kernel oils obtained from nine apricot varieties
      grown in the Malatya region of Turkey were determined ( P<0.05). The names of the
      apricot varieties were Alyanak (ALY), Cataloglu (CAT), Cologlu (COL),
      Hacihaliloglu (HAC), Hacikiz (HKI), Hasanbey (HSB), Kabaasi (KAB), Soganci (SOG),
      and Tokaloglu (TOK). The total oil contents of apricot kernels ranged from 40.23
      to 53.19%. Oleic acid contributed 70.83% to the total fatty acids, followed by
      linoleic (21.96%), palmitic (4.92%), and stearic (1.21%) acids. The s n-2
      position is mainly occupied with oleic acid (63.54%), linoleic acid (35.0%), and
      palmitic acid (0.96%). Eight TAG species were identified: LLL, OLL, PLL, OOL+POL,
      OOO+POO, and SOO (where P, palmitoyl; S, stearoyl; O, oleoyl; and L, linoleoyl),
      among which mainly OOO+POO contributed to 48.64% of the total, followed by
      OOL+POL at 32.63% and OLL at 14.33%. Four tocopherol and six phytosterol isomers
      were identified and quantified; among these, gamma-tocopherol (475.11 mg/kg of
      oil) and beta-sitosterol (273.67 mg/100 g of oil) were predominant. Principal
      component analysis (PCA) was applied to the data from lipid components of apricot
      kernel oil in order to explore the distribution of the apricot variety according
      to their kernel's lipid components. PCA separated some varieties including ALY,
      COL, KAB, CAT, SOG, and HSB in one group and varieties TOK, HAC, and HKI in
      another group based on their lipid components of apricot kernel oil. So, in the
      present study, PCA was found to be a powerful tool for classification of the
      samples.

PMID- 18038981
TI  - Production and characterization of films from cotton stalk xylan.
AB  - Composite film production based on cotton stalk xylan was studied, and the
      mechanical and physical properties of the films formed were investigated. Xylan
      and lignin were separated from cellulose by alkali extraction and, then, lignin
      was removed using ethanol washing. Self-supporting continuous films could not be
      produced using pure cotton stalk xylan. However, film formation was achieved
      using 8-14% (w/w) xylan without complete removal of lignin during xylan
      isolation. Keeping about 1% lignin in xylan (w/w) was determined to be sufficient
      for film formation. Films were produced by casting the film-forming solutions,
      followed by solvent evaporation in a temperature (20 degrees C) and relative
      humidity (40%) controlled environment. The elastic modulus and hypothetical
      coating strength of the films obtained by using 8% xylan were significantly
      different from the ones containing 10-14% xylan. The water vapor transfer rates
      (WVTR) decreased with increasing xylan concentration, which made the films
      thicker. The glycerol addition as an additional plasticizer resulting in more
      stretchable films having higher WVTR and lower water solubility values. As a
      result, film production was successfully achieved from xylan, which was extracted
      from an agricultural waste (cotton stalk), and the film-forming effect of lignin
      on pure xylan has been demonstrated.

PMID- 18038982
TI  - Oxidative DNA damage preventive activity and antioxidant potential of Stevia
      rebaudiana (Bertoni) Bertoni, a natural sweetener.
AB  - At 0.1 mg/mL, the ethyl acetate extract (EAE) of the crude 85% methanolic extract
      (CAE) of Stevia rebaudiana leaves exhibited preventive activity against DNA
      strand scission by *OH generated in Fenton's reaction on pBluescript II SK (-)
      DNA. Its efficacy is better than that of quercetin. The radical scavenging
      capacity of CAE was evaluated by the DPPH test (IC50=47.66+/-1.04 microg/mL). EAE
      was derived from CAE scavenged DPPH (IC50=9.26+/-0.04 microg/mL), ABTS+
      (IC50=3.04+/-0.22 microg/mL) and *OH (IC50=3.08+/-0.19 microg/mL). Additionally,
      inhibition of lipid peroxidation induced with 25 mM FeSO 4 on rat liver
      homogenate as a lipid source was noted with CAE (IC50=2.1+/-1.07 mg/mL). The
      total polyphenols and total flavonoids of EAE were 0.86 mg gallic acid
      equivalents/mg and 0.83 mg of quercetin equivalents/mg, respectively. Flavonoids,
      isolated from EAE, were characterized as quercetin-3-O-arabinoside, quercitrin,
      apigenin, apigenin-4-O-glucoside, luteolin, and kaempferol-3-O-rhamnoside by LC
      MS and NMR analysis. These results indicate that Stevia rebaudiana may be useful
      as a potential source of natural antioxidants.

PMID- 18038983
TI  - Apple peel as a contributor to whole fruit quantity of potentially healthful
      bioactive compounds. Cultivar and year implication.
AB  - On the basis of the fresh weight of apple fruit and its peel and the
      concentration of bioactive compounds, the total quantity of L-cysteine,
      glutathione, ascorbate, flavonols, and anthocyanins as well as phenolics was
      evaluated in a wide range of cultivars and two growing seasons. Apple peel as a
      contributor to the entire apple quantity of the examined components considerably
      differed in relation to the investigated compounds and was also highly cultivar
      dependent. A great amount of flavonols was found in apple peel (approximately
      40%), followed by ascorbate (approximately 30%) and total phenolics
      (approximately 20%), while the lowest contribution was assessed for thiols
      (approximately 11% and 14% for L-cysteine and total quantity of glutathione,
      respectively), based on average values for both years. Seasonal variations in the
      quantity of antioxidants was more pronounced in apple peel, whereas the
      contribution of apple peel to the whole fruit was predominantly affected by the
      genotype. A very high positive correlation existed between apple peel and the
      whole fruit quantity of antioxidants.

PMID- 18038984
TI  - In vitro digestibility of the cancer-preventive soy peptides lunasin and BBI.
AB  - Lunasin and BBI (Bowman Birk protease inhibitor) are bioactive soy peptides that
      have been shown to be effective suppressors of carcinogenesis in in vitro and in
      vivo model systems. Since they are subject to digestion in the gastrointestinal
      tract, we investigated here the stabilities of lunasin and BBI to digestion in
      vitro by simulated intestinal fluid (SIF) and simulated gastric fluid (SGF).
      Samples containing lunasin and BBI of varying purities were subjected to in vitro
      digestion by SIF and SGF at different times and analyzed by Western blot. While
      the pure BBI reaction is stable after SIF and SGF digestions, the purified
      lunasin from soybean and synthetic lunasin are easily digested after 2 min in
      both in vitro digestions. In contrast, lunasin from soy protein containing BBI is
      comparatively stable after SIF and SGF digestions. Both lunasin and BBI are able
      to internalize into the cell and localize in the nucleus even after digestion,
      suggesting that some of the peptides are intact and bioactive. These data suggest
      that BBI plays a role in protecting lunasin from digestion when soy protein is
      consumed orally. The role of other soy protease inhibitors such as Kunitz Trypsin
      Inhibitor (KTI) cannot be excluded from these experiments.

PMID- 18038985
TI  - Changes in the concentrations of free fatty acid, monoacylglycerol, and
      diacylglycerol in the subcutaneous fat of Iberian ham during the dry-curing
      process.
AB  - Changes in diacylglycerols, monoacylglycerols, and free fatty acid composition of
      subcutaneous fat of six Iberian hams during the dry-cured process were
      investigated. In addition, an analytical method for simultaneous quantification
      of diacylglycerols, monoacylglycerols, and free fatty acid by solid-phase
      extraction-gas chromatography was developed. The different molecular species of
      free fatty acids, monoacylglycerols, and diacylglycerols and 1,2- and 1,3-isomers
      of diacylglycerols have been described for the first time in this type of sample.
      A logarithmic increase of the 1,3-diacylglycerol profile throughout the
      processing time has been found, reaching a balance value of 62% around 500 days.
      The formation of diacylglycerol isomers takes place, although the 1,3-/1,2
      diacylglycerol ratio increases during the process to 1.65 due to isomerization of
      the 1,2-form toward the 1,3-form. The profiles of monoacyl- and diacylglycerols
      and free fatty acids follow the same trend. The experimental values of free fatty
      acid are greater than theoretical prediction, probably due to phospholipid and
      monoacylglycerol hydrolysis.

PMID- 18038986
TI  - Changes in the fatty acid profile of the subcutaneous fat of swine throughout
      fattening as affected by dietary conjugated linoleic acid and monounsaturated
      fatty acids.
AB  - The fatty acid profile of the subcutaneous fat of pigs and its evolution
      throughout fattening as affected by dietary conjugated linoleic acid (CLA),
      monounsaturated fatty acids (MUFA), and their interaction (CLAxMUFA) were
      studied. Three levels (0, 1, and 2%) of an enriched CLA oil (28% cis-9, trans-11
      and 28% trans-10, cis-12 CLA) were combined with two levels of MUFA (low, 19%
      average; and high, 39% average) for pig feeding (288 gilts). Subcutaneous shot
      biopsies were taken from 48 animals at the beginning of the trial (S1, 70 kg), 14
      days later (S2, 80 kg), and at slaughter (S3, 107 kg). Inclusion of CLA in the
      diet caused an increase during fattening in cis-9, trans-11 CLA, trans-10, cis-12
      CLA, and saturated fatty acids (SFA) contents of pig backfat and a decrease in
      MUFA and polyunsaturated fatty acids (PUFA). MUFA supplementation also led to a
      MUFA enrichment of backfat. The interaction CLAxMUFA affected the SFA content.
      The rates of accumulation of CLA isomers, SFA, and MUFA throughout the trial did
      not follow a linear behavior, such rates being higher from S1 to S2 than from S2
      to S3. These rates were also influenced by dietary CLA and MUFA levels. The
      increase in the ratio of saturated to unsaturated fatty acids of backfat caused
      by dietary CLA might be balanced by supplementation of pig diets with MUFA.

PMID- 18038987
TI  - Acid gelation properties of heated skim milk as a result of enzymatically induced
      changes in the micelle/serum distribution of the whey protein/kappa-casein
      aggregates.
AB  - Changes in the acid gelation properties of skim milk as a result of variations in
      the micelle/serum distribution of the heat-induced whey protein/kappa-casein
      aggregates, induced by the combination of heat treatment and limited renneting,
      were investigated. No dramatic change in the zeta potential or the isoelectric
      point of the casein micelles was suggested, whether the aggregates were all
      attached to the casein micelle or not. Fluorescence intensity measurement using 8
      anilino-1-naphthalenesulfonic acid (ANS) showed that the heat-induced aggregates
      were highly hydrophobic. Dynamic oscillation viscosimetry showed that acid
      gelation using glucono-delta-lactone (GDL) started at a higher pH value in
      prerenneted milk. However, no change in the gelation profile of skim milk could
      be related to the proportion of aggregates bound to the surface of the casein
      micelles. The results support the idea of an early interaction between the serum
      aggregates and the casein micelles on acidification.

PMID- 18038988
TI  - Changes in the antioxidative property of herring (Clupea harengus) press juice
      during a simulated gastrointestinal digestion.
AB  - The aqueous fraction (press juice, PJ) from herring muscle was recently shown to
      inhibit hemoglobin-mediated oxidation of washed fish mince lipids during ice
      storage. As a first step to evaluate potential in vivo antioxidative effects from
      herring PJ, the aim of this study was to investigate whether herring PJ retains
      its antioxidative capacity during a simulated gastrointestinal (GI) digestion.
      Press juice from whole muscle (WMPJ) and light muscle (LMPJ) was mixed with
      pepsin solution followed by stepwise pH adjustments and additions of pancreatin
      and bile solutions. Digestive enzymes were removed from samples by
      ultrafiltration (10 kDa). Before, during, and after digestion, samples were
      analyzed for their peptide content and for antioxidative properties with the
      oxygen radical absorbance capacity (ORAC) and the low-density lipoprotein (LDL)
      oxidation assays. From 0 to 165 min of digestion, the content of <10 kDa peptides
      in WMPJ and LMPJ samples increased 12- and 7-fold, respectively. Further, both
      samples got approximately 12.5 times higher ORAC values and gave rise to
      approximately 1.3-fold increased lag phase in Cu2+-induced LDL oxidation. The
      largest changes in peptide content, ORAC values, and LDL oxidation inhibition
      occurred between 30 and 75 min of digestion, indicating that these parameters
      might be interrelated. When comparing analytical data obtained after 165 min of
      digestion with data obtained from analyses of native nondigested PJs, it was
      found that the data on peptide content, ORAC, and LDL oxidation from digested PJs
      were 64-69%, 121-161%, and 112-115%, respectively, of those of nondigested PJs.
      The study thus showed that enzymatic breakdown of PJ proteins under GI-like
      conditions increases the peroxyl radical scavenging activity and the potential to
      inhibit LDL oxidation of herring PJs. These data provide a solid basis for
      further studies of uptake and in vivo activities of herring-derived aqueous
      antioxidants.

PMID- 18038989
TI  - Changes in polyphenolic content and radical-scavenging activity of sweet potato
      (Ipomoea batatas L.) during storage at optimal and low temperatures.
AB  - Polyphenolic content and radical-scavenging activities (RSA) of four sweet potato
      (Ipomoea batatas L.) cultivars were characterized after storage at optimal (15
      degrees C) or low temperature (5 degrees C) for 0, 13, 26, and 37 days. The
      polyphenolic content increased during storage in three cultivars but not in
      'Murasakimasari'. The change in 1,1-diphenyl-2-picrylhydrazyl radical-scavenging
      activity (DPPH-RSA) correlated very well with polyphenolic content. The increases
      in polyphenolics and the RSA in 'Benimasari' were significantly greater during
      storage at 5 degrees C than at 15 degrees C. The main polyphenolic components in
      all cultivars were chlorogenic acid (ChA) and 3,5-di-O-caffeoylquinic acid (3,5
      diCQA). ChA level increased more at 5 degrees C than at 15 degrees C, whereas
      that of 3,5-diCQA was greater at 15 degrees C. Caffeoylquinic acids and RSA in
      'Murasakimasari', which contains a large amount of anthocyanin in flesh tissue,
      were extremely high at the beginning of storage and remained nearly constant or
      decreased over time. A non-caffeoylquinic acid component that increased during
      storage, especially in 'J-Red' at 15 degrees C, was purified by successive
      chromatographic steps. The isolate was identified as caffeoyl sucrose [CSu, 6-O
      caffeoyl-(beta- d-fructofuranosyl-(2-->1))-alpha-D-glucopyranoside] by fast atom
      bombardment-mass spectroscopy (FAB-MS), infrared spectroscopy (IR), and nuclear
      magnetic resonance spectroscopy (NMR). These results suggest that storage under
      cultivar-dependent, controlled temperature is one approach for increasing
      desirable physiologic function associated with RSA of polyphenolic compounds in
      sweet potato roots.

PMID- 18038990
TI  - Evolution of phenolic compounds and antioxidant activity during malting.
AB  - Two barley varieties, Gan4 and Hamelin, were malted to investigate the evolution
      of phenolic compounds and antioxidant activity during malting. The antioxidant
      activity was evaluated with DPPH radical scavenging activity, ABTS radical cation
      scavenging activity, reducing power, and metal chelating activity. Results showed
      that malting had significant influences on individual and total phenolic contents
      as well as antioxidant activities of two barley varieties. The contents of some
      phenolic compounds and the antioxidant activities decreased significantly during
      steeping and the early stages of germination and then increased remarkably during
      the later stages of germination and subsequent kilning. The most phenolic
      compounds identified in barley were (+)-catechin and ferulic acid, which both
      changed significantly during malting. Moreover, results from the Pearson
      correlation analysis showed that there were good correlations among DPPH radical
      scavenging activity, ABTS radical cation scavenging activity, reducing power,
      total phenolic content and sum of individual phenolic contents during malting.

PMID- 18038991
TI  - Variability in the release of free and bound hydroxycinnamic acids from diverse
      malted barley (Hordeum vulgare L.) cultivars during wort production.
AB  - Volatile phenols have long been recognized as important flavor contributors to
      the aroma of various alcoholic beverages. The two main flavor-active volatile
      phenols in beer are 4-vinylguaiacol and 4-vinylphenol. They are the
      decarboxylation products of the precursors ferulic acid and p-coumaric acid,
      respectively, which are released during the brewing process, mainly from malt. In
      this study, the variability in the release of free and ester-bound
      hydroxycinnamic acids from nine malted barley ( Hordeum vulgare L.) varieties
      during wort production was investigated. A large variability between different
      barley malts and their corresponding worts was observed. Differences were also
      found between free ferulic acid levels from identical malt varieties originating
      from different malt houses. During mashing, free hydroxycinnamic acids in wort
      are both water-extracted and enzymatically released by cinnamoyl esterase
      activity. Esterase activities clearly differ between different barley malt
      varieties. Multiple linear regression analysis showed that the release of ferulic
      acid during mashing did not depend only on the barley malt esterase activity but
      also on the amount of ester-bound ferulic acid initially present in the wort and
      on its endoxylanase activity. The study demonstrates the importance of selecting
      a suitable malt variety as the first means of controlling the final volatile
      phenol levels in beer.

PMID- 18038992
TI  - Lupine induced "crooked calf disease" in Washington and Oregon: identification of
      the alkaloid profiles in Lupinus sulfureus, Lupinus leucophyllus, and Lupinus
      sericeus.
AB  - Several lupines (Lupinus spp.) present on western U.S. rangelands contain
      alkaloids that are teratogenic to livestock and cause congenital birth defects in
      calves (crooked calf disease). Periodically, large losses of calves due to lupine
      induced "crooked calf disease" occur in northern Oregon and eastern Washington
      state. Five lupine populations from this area representing three species (L.
      leucophyllus, L. sulfureus, and L. sericeus) were evaluated taxonomically and by
      gas chromatography/mass spectrometry, and the major alkaloids in each lupine
      species were identified. The teratogenic alkaloid anagyrine was present in both
      of the lupine species responsible for the high outbreaks in east-central
      Washington and northeastern Oregon. However, the alkaloid profiles of the two
      lupines identified as L. leucophyllus were dissimilar, as were the alkaloid
      profiles of the two lupines identified as L. sulfureus. Botanical classification
      is not sufficient to determine potential teratogenicity, and it must be followed
      by chemical characterization to determine risk to livestock.

PMID- 18038993
TI  - Cancer-preventive peptide lunasin from Solanum nigrum L. inhibits acetylation of
      core histones H3 and H4 and phosphorylation of retinoblastoma protein (Rb).
AB  - Lunasin, a unique 43 amino acid, 4.8 kDa cancer-chemopreventive peptide initially
      reported in soybean and now found in barley and wheat, has been shown to be
      cancer-chemopreventive in mammalian cells and in a skin cancer mouse model
      against oncogenes and chemical carcinogens. To identify bioactive components in
      traditional herbal medicines and in search for new sources of lunasin, we report
      here the properties of lunasin from Solanum nigrum L. (SNL), a plant indigenous
      to northeast Asia. Lunasin was screened in the crude extracts of five varieties
      of the medicinal plants of Solanaceae origin and seven other major herbal plants.
      An in vitro digestion stability assay for measuring bioavailability was carried
      out on SNL crude protein and autoclaved SNL using pepsin and pancreatin. A
      nonradioactive histone acetyltransferase (HAT) assay and HAT activity
      colorimetric assay were used to measure the inhibition of core histone
      acetylation. The inhibitory effect of lunasin on the phosphorylation of
      retinoblastoma protein (Rb) was determined by immunoblotting against phospho-Rb.
      Lunasin isolated from autoclaved SNL inhibited core histone H3 and H4
      acetylation, the activities of the HATs, and the phosphorylation of the Rb
      protein. Lunasin in the crude protein and in the autoclaved crude protein was
      very stable to pepsin and pancreatin in vitro digestion, while the synthetic pure
      lunasin was digested at 2 min after the reaction. We conclude that lunasin is a
      bioactive and bioavailable component in SNL and that consumption of SNL may play
      an important role in cancer prevention.

PMID- 18038994
TI  - Impact of physicochemical characteristics on the oxidative stability of fish oil
      microencapsulated by spray-drying.
AB  - The aim of the present research was to identify principal parameters determining
      the oxidative stability of microencapsulated fish oil. Microcapsules were
      prepared by spray-drying using different types of n-octenylsuccinate-derivatized
      starch, gum Arabic, sugar beet pectin, sodium caseinate, and/or glucose syrup.
      Two principal components to classify the different microcapsules accounting for
      up to 79% of the variance were identified. The principal components were
      determined by physicochemical parameters reflecting the emulsifying ability of
      the encapsulant and the drying behavior of the parent emulsion. Microcapsules,
      which were identified by principal component analysis to be significantly
      different, exhibited a low stability upon storage, showing that the principal
      components and, thus, the underlying physicochemical parameters analyzed in the
      present study are correlated with core material stability.

PMID- 18038995
TI  - Verification of silage type using near-infrared spectroscopy combined with
      multivariate analysis.
AB  - The ability to authenticate the feed given to animals has become a major
      challenge in animal production, where the diet fed to the animal is one of the
      most important production factors affecting the composition of milk and meat from
      cattle, sheep, and goats. Hence, there is currently an increased consumer demand
      for information on herbivore production factors and particularly the animal diet.
      The aim of this study was to evaluate the reliability and accuracy of near
      infrared (NIR) reflectance spectroscopy as a tool to verify and authenticate the
      type of silage used as fed for ruminants. Grain silage (GrS, n = 94), grass and
      legume silage (GLegS, n = 121), and sunflower silage (SunS, n = 50) samples were
      collected from commercial farms and analyzed in the visible and NIR regions (400
      2500 nm) in a monochromator instrument in reflectance. Principal component
      analysis (PCA), partial least-squares discriminant analysis (PLS1-DA), and linear
      discriminant analysis (LDA) models were used as methods to verify the different
      silage types. The classification models based on the NIR data correctly
      classified more than 90% of the silage samples according to their type. The
      results from this study showed that NIR spectra combined with multivariate
      analysis could be used as a tool to objectively authenticate silage samples used
      as a feed for ruminants.

PMID- 18038996
TI  - Ability of surface-active antioxidants to inhibit lipid oxidation in oil-in-water
      emulsion.
AB  - Lipid oxidation in dispersed lipids is prevalent at the oil-water interface where
      lipid hydroperoxides are decomposed into free radicals by transition metals. Free
      radical scavenging antioxidants are believed to be most effective in lipid
      dispersions when they accumulate at the oil-water interface. The surface activity
      of antioxidants could be increased by their conjugation to hydrocarbon chains. In
      this study, p-hydroxyphenylacetic acid (HPA) was conjugated with either a butyl
      or dodecyl group. The HPA conjugates were more effective at decreasing
      interfacial tension than unconjugated HPA, indicating that they were able to
      adsorb at lipid-water interfaces. However, free HPA was a more effective
      antioxidant than butyl and dodecyl conjugates in Menhaden oil-in-water emulsions
      as determined by both lipid hydroperoxides and thiobarbituric acid reactive
      substances. The increased antioxidant activity of free HPA could be due to its
      more effective free radical scavenging activity and its higher concentration in
      the lipid phase of oil-in-water emulsions in the presence of surfactant micelles
      where it can act as a chain-breaking antioxidant.

PMID- 18038997
TI  - Isolation and identification of two lipid transfer proteins in pomegranate
      (Punica granatum).
AB  - Lipid transfer proteins (LTPs) are a family of low molecular mass (7-9 kDa)
      polypeptides, the members of which share 35-95% sequence homology. These proteins
      are widely distributed throughout the plant kingdom and are receiving attention
      for their biochemical characteristics and biological activity. LTPs are indeed
      studied in different research fields varying from allergy to food technology, and
      numerous molecules belonging to this class are progressively being identified and
      investigated. Proteins from pomegranate juice were fractioned by cation exchange
      chromatography and analyzed by SDS-PAGE. Two proteins were identified as putative
      LTPs on the basis of their molecular weights and their electrophoretic behaviors
      under reducing and nonreducing conditions. Finally, proteins were purified and
      characterized by mass spectrometry. This analysis confirmed that the two
      polypeptides are LTPs on the basis of an amino acid sequence common to LTPs from
      other plant sources and cysteine content. The two proteins, named LTP1a and
      LTP1b, showed similar molecular masses but different immunological profiles when
      immunodetected with rabbit antibodies specific for Pru p 3 and human IgE from a
      patient suffering from pomegranate allergy. The demonstration of the existence of
      two immunologically unrelated LTPs in pomegranate confirms the variability and
      the complexity of the plant LTP family. This should be taken into account when
      the role of these proteins as elicitors of allergies to fruits is investigated
      and could help to explain the contradictory literature data on pomegranate
      allergy.

PMID- 18038998
TI  - Structure-antifungal activity relationship of cinnamic acid derivatives.
AB  - A structure-antifungal activity relationship (SAR) study of 22 related cinnamic
      acid derivatives was carried out. Attention was focused on the antifungal
      activities exhibited against Aspergillus flavus, Aspergillus terreus, and
      Aspergillus niger. (E)-3-(4-methoxy-3-(3-methylbut-2-enyl)phenyl)acrylic acid
      (16) exhibited antifungal activity against A. niger, comparable to that of
      miconazole and a significant antifungal effect against A. flavus and A. terreus
      as well. A structure-activity relationship (SAR) study of related cinnamic acid
      derivatives has allowed a model to be proposed for the recognition of the minimal
      structural requirements for the antifungal effect in this series.

PMID- 18038999
TI  - Effect of polymer amphiphilicity on loading of a therapeutic enzyme into
      protective filamentous and spherical polymer nanocarriers.
AB  - Rapid clearance and proteolysis limit delivery and efficacy of protein
      therapeutics. Loading into biodegradable polymer nanocarriers (PNC) might protect
      proteins, extending therapeutic duration, but loading can be complicated by
      protein unfolding and inactivation. We encapsulated active enzymes into methoxy
      poly(ethylene glycol- block-lactic acid) (mPEG-PLA) PNC with a freeze-thaw double
      emulsion ( J. Controlled Release 2005, 102 (2), 427-439). On the basis of
      concepts of amphiphile self-assembly, we hypothesized that the copolymer block
      ratio that controls spontaneous curvature would influence PNC morphology and
      loading. We examined PNC yield, shape, stability, loading, activity, and protease
      resistance of the antioxidant enzyme, catalase. PNC transitioned from spherical
      to filamentous shapes with increasing hydrophobic polymer fraction, consistent
      with trends for self-assembly of lower MW amphiphiles. Importantly, one diblock
      copolymer formed filamentous particles loaded with significant levels of protease
      resistant enzyme, demonstrating for the first time encapsulation of an active
      therapeutic enzyme into filamentous carriers. PNC morphology also greatly
      influenced its degradation, offering a new means of controlled delivery.

PMID- 18039000
TI  - Functionalization of poly(oligo(ethylene glycol) methacrylate) films on gold and
      Si/SiO2 for immobilization of proteins and cells: SPR and QCM studies.
AB  - Thin films of a biocompatible and nonbiofouling poly(oligo(ethylene glycol)
      methacrylate) ( pOEGMA) with various thicknesses were formed on gold and Si/SiO 2
      substrates by a combination of the formation of self-assembled monolayers (SAMs)
      terminating in bromoester-an initiator of atom transfer radical polymerization
      (ATRP)-and surface-initiated ATRP. After the formation of the pOEGMA films,
      terminal hydroxyl groups of side chains divergent from the methacrylate backbones
      were activated with N, N'-disuccinimidyl carbonate (DSC), and the DSC-activated
      pOEGMA films were reacted with (+)-biotinyl-3,6,9-trioxaundecanediamine (Biotin
      NH 2) to form biotinylated pOEGMA films. By surface plasmon resonance experiments
      with the target protein (streptavidin) and model proteins (fibrinogen and
      lysozyme), we verified that the resulting films showed the enhanced signal-to
      noise ratio ( approximately 10-fold enhancement) for the biospecific binding of
      streptavidin compared with the biotinylated substrate prepared from carboxylic
      acid-terminated SAMs. Quartz crystal microbalance measurements were also carried
      out to obtain the surface coverage of streptavidin and fibrinogen adsorbed onto
      the biotinylated pOEGMA films with various thicknesses and to investigate the
      effect of film thicknesses on the biospecific binding of streptavidin. Both the
      binding capacity of streptavidin and the signal-to-noise ratio of
      streptavidin/fibrinogen were found to be saturated at the 20 nm thick pOEGMA
      film. In addition, to demonstrate a wide applicability of the pOEGMA films, we
      constructed micropatterns of streptavidin and cells by microcontact-printing
      biotin-NH 2 and poly- l-lysine onto the DSC-activated pOEGMA films, respectively.

PMID- 18039001
TI  - Hyaluronate-covered nanoparticles for the therapeutic targeting of cartilage.
AB  - Hyaluronic acid (HA) has a high affinity for the CD44 receptor present at the
      surface of articular cells, particularly of chondrocytes. HA-covered polylactide
      nanoparticles containing bioactive compounds such as HA and chondroitin sulfate
      (CS) were thus prepared in order to achieve a controlled delivery targeted to
      cartilage cells after injection near articular alterations/erosions. Such
      nanoparticles (diameter = 700 nm) were prepared by double emulsion/solvent
      evaporation, using amphiphilic derivatives of HA, as stabilizer of the secondary
      emulsion. These nanoparticles were incubated with articular cells, and several
      tests were carried out. First, they proved that the nanospheres provoked no
      decrease in cell viability, even after 72 h of contact. Second, a confocal
      microscopy analysis on fluorescent HA-covered particles showed that they were
      captured by articular cells, while with those covered with poly(vinyl alcohol),
      the uptake was far lower. Third, a scattering electron microscopy analysis proved
      that the HA-coated nanoparticles were localized in the cell intracytoplasmic
      area.

PMID- 18039002
TI  - Thermal dependence of thermally induced protein spherulite formation and growth:
      kinetics of beta-lactoglobulin and insulin.
AB  - Amyloid fibril forming proteins have been related to some neurodegenerative
      diseases and are not fully understood. In some such systems, these amyloid
      fibrils have been found to form radially oriented spherulite structures. The
      thermal dependence of formation and growth of these spherulite structures in two
      model protein systems, beta-lactoglobulin and insulin at low pH aqueous and high
      temperature conditions, have been monitored with time-lapse optical microscopy
      and quantified. A population-based polymerization reaction model was developed
      and applied to the experimental data with excellent agreement. While spherulites
      in the insulin solutions formed and grew at approximately 25x the rate of
      spherulites in the beta-lactoglobulin solutions, the temperature dependence and
      activation energies of both systems were found to be very similar to one another,
      suggesting that the underlying rate-limiting mechanisms for both formation and
      growth are consistent across the two systems. The similarity of both of these
      amyloid fibril forming protein systems provides confidence in their use as model
      systems for extrapolating understanding to similar systems involved in
      neurodegenerative diseases.

PMID- 18039003
TI  - Carrageenan as an efficient drug release modifier for ethylcellulose-coated
      pharmaceutical dosage forms.

PMID- 18039004
TI  - Structure and mechanical properties of hydroxypropylated starch films.
AB  - Films of acid-hydrolyzed hydroxypropylated pea starch with average molecular
      weight M w ranging from 3.3 x 10 (4) g/mol to 1.6 x 10 (6) g/mol were prepared
      from 25% (w/w) solution by casting. The structure of the films was investigated
      by means X-ray diffraction and calorimetry, evidencing a B-type crystalline
      structure. In similar drying conditions, 25 degrees C and 40% of relative
      humidity, the crystallinity varied from 24% for the low molecular weight (A5) to
      almost none for the highest molecular weight (A160). The influence of the drying
      temperature was also investigated. A reduction of the crystallinity from 16% to
      almost none was found when increasing temperature from 25 to 65 degrees C. The
      glass transition temperature ( T g) at different water contents was determined.
      The difference of T g between the first and the second scan was interpreted by
      changes in the water distribution between phases into the B-type crystalline
      structure. Mechanical properties of the films determined by tensile tests and by
      DMTA in the glassy state showed no effect of the average molecular weight or of
      crystallinity. In contrast, thermomechanical experiments by DMTA showed that the
      average molecular weight of the sample influenced the mechanical relaxation and
      the moduli in the rubbery state.

PMID- 18039005
TI  - PCL-PEG-based nanoparticles grafted with GRGDS peptide: preparation and surface
      analysis by XPS.

PMID- 18039006
TI  - Genetic engineering of self-assembled protein hydrogel based on elastin-like
      sequences with metal binding functionality.
AB  - Recombinant DNA methods have been exploited to enable the creation of protein
      based block copolymers with programmable sequences, desired properties, and
      predictable three-dimensional structures. These advantages over conventional
      polymer counterparts facilitate the utility of this new class of biomaterials in
      a wide range of applications. In this project, we exploited the environmental
      application of protein-based block copolymers based on elastin-like protein (ELP)
      sequences. Triblock copolymers containing charged and hydrophobic segments were
      synthesized. Chain lengths of each segment were manipulated in order to maintain
      a gelation point below room temperature. Polyhistidine sequences were
      successfully incorporated into the hydrophilic segment without disruption of the
      self-assembled hydrogel formation. The microscopic structure was further
      investigated using laser confocal microscopy. The metal binding capability and
      capacity of resulting hydrogel were studied to demonstrate the functionality of
      polyhistidine and its environmental application for heavy metal removal.
      Reversibility of metal binding was demonstrated, indicating the cost
      effectiveness of this hydrogel. Significantly, we envision that this versatile
      strategy of incorporating functional groups within a 3-D protein network provides
      new possibilities in creation of biomaterials with great control over structure
      property relationships.

PMID- 18039007
TI  - Specificity and mobility of biomacromolecular, multivalent constructs for
      cellular targeting.
AB  - Effective targeting of drugs to cells requires that the drug reach the target
      cell and interact specifically with it. In this study, we synthesized a
      biomacromolecular, multivalent construct intended to target glioblastoma tumors.
      The construct was created by linking three dodecapeptides, reported to bind the
      alpha 6beta1 integrin, with poly(ethylene glycol) linkers. The construct is
      intended to be delivered locally, and it demonstrates a more homogeneous and more
      rapid perfusion profile in comparison with quantum dots. The binding specificity
      of the construct was investigated by using glioblastoma cells and normal human
      astrocyte cells. The results reveal qualitative differences in binding between
      glioma and normal human astrocyte cells, with a moderate increase in binding
      avidity due to multivalency (0.79 microM for the trivalent construct versus 4.28
      microM for the dodecapeptide). Overall, biomacromolecular constructs appear to be
      a promising approach for targeting with high biocompatibility, good perfusion
      abilities, and specificity.

PMID- 18039008
TI  - Extraction and precipitation of chitosan from cell wall of zygomycetes fungi by
      dilute sulfuric acid.
AB  - A new method was developed in this work for extraction of chitosan from the
      zygomycetes cell wall. It is based on the temperature-dependent solubility of
      chitosan in dilute sulfuric acid. Chitin is soluble in neither cold nor hot
      dilute sulfuric acid. Similarly chitosan is not soluble at room temperature but
      is dissolved in 1% H 2SO 4 at 121 degrees C within 20 min. The new method was
      developed to measure the chitosan content of the biomass and cell wall. The
      procedures were investigated by measuring phosphate, protein, ash, glucuronic
      acid, and degree of acetylation. The cell wall derivatives of fungus Rhizomucor
      pusillus were then examined by this new method. The results indicated 8% of the
      biomass as chitosan. After treatment with NaOH, the alkali-insoluble material
      (AIM) contained 45.3% chitosan. Treatment of AIM with acetic acid resulted in
      16.5% acetic-acid-soluble material (AcSM) and 79.0% alkali- and acid-insoluble
      material (AAIM). AcSM is usually cited as pure chitosan, but the new method shows
      major impurities by, for example, phosphate. Furthermore, AAIM is usually
      considered to be the chitosan-free fraction, whereas the new method shows more
      than 76% of the chitosan present in AIM is found in AAIM. It might indicate the
      inability of acetic acid to separate chitosan from the cell wall.

PMID- 18039009
TI  - Ecdysteroids from the Antarctic tunicate Synoicum adareanum.
AB  - Five new ecdysteroids, hyousterones A-D (2-5) and abeohyousterone (6), have been
      isolated from the Antarctic tunicate Synoicum adareanum along with the known
      ecdysteroid diaulusterol B (1). Hyousterones B (3) and D (5) are unusual
      ecdysteroids in bearing the 14beta-hydroxyl group, and abeohyousterone
      incorporates the 13(14-->8) abeo steroid skeleton, reflecting a rearrangement of
      the steroid C/D ring system. Abeohyousterone has moderate cytotoxicity toward
      several cancer cell lines. Hyousterones bearing the 14alpha-hydroxy group (2 and
      4) were weakly cytotoxic, while the 14beta-hydroxy hyousterones (3 and 5) were
      devoid of cytotoxicity. The 14beta-hydroxy function may be a thermodynamic
      pathway to the 13(14-->8) abeo steroid skeleton. Hyousterones, abeohyousterone,
      and diaulusterol B are the first ecdysteroids reported from tunicates.

PMID- 18039010
TI  - Alkaloids with human delta-opioid receptor binding affinity from the Australian
      rainforest tree Peripentadenia mearsii.
AB  - Three new pyrrolidine alkaloids, peripentonine A-C ( 2- 4), one known pyrrolidine
      alkaloid, peripentadenine ( 1), and one novel indolizidine alkaloid, mearsamine (
      5), were isolated from the leaves of Peripentadenia mearsii and their structures
      determined by 1D and 2D NMR spectroscopy. Peripentonines A ( 2) and B ( 3) were
      isolated as a 1:1 mixture of inseparable diastereomers. Mearsamine ( 5) contains
      a novel tricyclic ring system. Peripentadenine and peripentonines A/B and C
      showed receptor binding affinity for the human delta-opioid receptor with IC 50
      values of 11.4, 69.2, and 30.9 microM, respectively. Mearsamine did not bind to
      the delta-opioid receptor.

PMID- 18039011
TI  - Brandisianins A-F, isoflavonoids isolated from Millettia brandisiana in a
      screening program for death-receptor expression enhancement activity.
AB  - In a screening study for natural products with tumor-selective apoptosis-inducing
      properties, six new isoflavonoids (1- 6), named brandisianins A-F, respectively,
      have been isolated from a MeOH extract of the dried leaves of Millettia
      brandisiana, together with five known compounds. The structures of the new
      compounds were elucidated by spectroscopic data interpretation. Among these
      compounds, brandisianin D (4) exhibited death-receptor 5 expression enhancement
      activity in a luciferase assay based in DLD-1/ SacI cells. The results suggest
      that brandisianin D (4) might overcome TRAIL-resistance by an increase in DR5
      expression.

PMID- 18039012
TI  - Ptilomycalin D, a polycyclic guanidine alkaloid from the marine sponge Monanchora
      dianchora.
AB  - A new polycyclic guanidine alkaloid, ptilomycalin D, and the known crambescidic
      acid were isolated from the marine sponge Monanchora dianchora collected in Nosy
      Be, northwest of Madagascar, in the Indian Ocean. The structures were elucidated
      using 1- and 2-D NMR and MS data, and their biogenetic implications are
      discussed.

PMID- 18039013
TI  - Inhibition of depurinating estrogen-DNA adduct formation by natural compounds.
AB  - Specific metabolites of estrogens, catechol estrogen-3,4-quinones, if produced in
      relatively large amounts, can become chemical carcinogens by reacting with DNA to
      form predominantly depurinating DNA adducts. Estradiol (E2)-3,4-quinone (Q)
      reacts with DNA to form predominantly the depurinating DNA adducts, 4
      hydroxyestradiol (OHE2)-1-N3Ade and 4-OHE 2-1-N7Gua. The depurinating adducts
      induce mutations by error-prone repair. We have conducted a study in which
      selected natural chemopreventing agents, N-acetylcysteine (NAcCys), melatonin,
      reduced lipoic acid, and resveratrol, have been tested for their ability to
      prevent the reaction of E(2)-3,4-Q with DNA. When DNA was incubated with E(2)-3,4
      Q or lactoperoxidase-activated 4-OHE2 in the presence of an antioxidant, the
      formation of the N3Ade and N7Gua adducts was reduced. E(2)-3,4-Q or
      lactoperoxidase-oxidized 4-OHE 2 (87 microM final concentration) was incubated
      with calf-thymus DNA and one of the antioxidants at different ratios (1:0, 1:0.3,
      1:1, and 1:3 with respect to E(2)-3,4-Q or 4-OHE2) at 37 degrees C. After 10 h,
      the DNA was precipitated, and the supernatant was analyzed by using
      ultraperformance liquid chromatography/tandem mass spectrometry (LC/MS/MS). As
      anticipated, resveratrol and melatonin did not affect the formation of the
      depurinating adducts when E(2)-3,4-Q was reacted with DNA in their presence. On
      the other hand, NAcCys and lipoic acid (reduced form) showed a significant
      inhibition of the formation of the depurinating adducts by E(2)-3,4-Q. With
      reaction of lactoperoxidase-activated 4-OHE2 with DNA, resveratrol achieved the
      highest level of inhibition, NAcCys and reduced lipoic acid produced moderate
      inhibition, and melatonin had the least inhibition. These results demonstrate
      that all four selected compounds can inhibit the formation of depurinating
      estrogen-DNA adducts and set the stage for studies of their ability to inhibit
      adduct formation and malignant transformation in mammary epithelial cells. This
      approach is highly useful for identifying agents to prevent the initiation of
      human cancers, especially breast and prostate cancer.

PMID- 18039015
TI  - Sphingosine-1-phosphate signaling and the skin.
AB  - Sphingolipids have long been viewed as rather passive structural components of
      cellular membranes. More recently, it has become evident that metabolism of
      sphingomyelin yields several lipid mediators that evoke diverse and specific
      responses in different cell types. One sphingomyelin derivate, sphingosine-1
      phosphate (S1P), has attracted particular attention for its effect on epidermal
      cells, which differs from those on most other cell types. S1P inhibits
      keratinocyte proliferation and induces keratinocyte differentiation and
      migration, suggesting a role for S1P in the re-epithelialization of wounds. The
      migratory response involves the phosphorylation and activation of Smad3. In
      epithelial tumors, S1P signaling has been linked with potential oncogenic
      effects, but has also been found to inhibit metastasis in a mouse melanoma model.
      S1P promotes endothelial cell survival, acts as a chemoattractant for vascular
      cells, and exerts a protective effect on the endothelial barrier. Conversely, S1P
      receptor knockout leads to embryonic lethality mainly due to impaired vascular
      maturation. S1P presumably modulates peripheral T-lymphocyte levels by
      stimulating their egress from lymphoid organs rather than by promoting T-cell
      proliferation. The S1P analog FTY720 (fingolimod) acts as a functional antagonist
      by inhibiting lymphocyte egress, and thus holds great promise as an
      immunosuppressant drug for the prevention of allograft rejection and treatment of
      T-lymphocyte-driven inflammatory skin diseases, such as lupus erythematosus,
      psoriasis, and atopic dermatitis. Topical use of S1P and other sphingosine
      compounds is also under investigation, particularly for the treatment of acne
      vulgaris.

PMID- 18039016
TI  - Eyebrow loss: clinical review.
AB  - Loss of eyebrow hair may come to the attention of the dermatologist as a
      presenting complaint or as an unexpected finding on routine physical examination.
      Because eyebrows serve important cosmetic and social roles, their loss can be
      quite distressing to patients. While eyebrow loss may be an isolated finding of
      no medical consequence, it may also be an initial manifestation of a systemic
      condition. Loss of eyebrows has numerous causes including primary dermatoses,
      endocrinopathies, autoimmune conditions, infections, neoplasms, trauma, exogenous
      agents, and genetic diseases. We present a systemic review of eyebrow loss,
      including an algorithm that can be used to direct the work-up of patients
      presenting with this condition.

PMID- 18039017
TI  - Palmar erythema.
AB  - Palmar erythema (PE), an often overlooked physical finding, is due to several
      physiologic or systemic pathologic states. PE can exist as a primary physiologic
      finding or as a secondary marker of systemic pathology. Primary or physiologic PE
      can be due to heredity, occurs in at least 30% of pregnant women as a result of
      associated alterations in the function of the skin and its microvasculature, or
      may be a diagnosis of exclusion (i.e. idiopathic PE). Secondary PE from systemic
      pathology encompasses a wide range of disease states. Twenty-three percent of
      patients with liver cirrhosis, from varying causes, can manifest PE as a result
      of abnormal serum estradiol levels. Patients with a rare neonatal liver disease
      such as Wilson disease and hereditary hemochromatosis may exhibit PE along with
      the other systemic manifestations of the genodermatoses. PE has been reported to
      occur in >60% of patients with rheumatoid arthritis and is associated with a
      favorable prognosis. Up to 18% of patients with thyrotoxicosis and 4.1% of
      patients with diabetes mellitus can have PE. This cutaneous manifestation of
      diabetes occurs more often than the more classic diseases such as necrobiosis
      lipoidica diabeticorum (0.6%). PE can be seen in early gestational syphilis and
      among patients with human T-lymphotrophic virus-1-associated myelopathy. Drug
      induced PE with hepatic damage has been documented with use of amiodarone,
      gemfibrozil, and cholestyramine, while topiramate and albuterol (salbutamol) have
      been reported to cause PE in the setting of normal liver function. Fifteen
      percent of patients with both metastatic and primary brain neoplasms may have PE.
      Increased levels of angiogenic factors and estrogens from solid tumors have been
      postulated as the cause of PE in such cases. Erythema ab igne can mimic PE, and
      patients with atopic diathesis are more likely to have PE than matched control
      subjects. Smoking and chronic mercury poisoning are environmental causes of PE.No
      treatment of primary PE is indicated. If medication is the cause of PE, the drug
      responsible should be discontinued if possible. Identification of PE related to
      underlying disorders should be followed by treatment of the underlying condition.
      In light of the numerous etiologies of PE, this article reviews the current
      literature and provides a framework to help guide the clinician in determining
      the cause of PE in patients presenting with this finding.

PMID- 18039018
TI  - Comparable efficacy and safety of various topical formulations of terbinafine in
      tinea pedis irrespective of the treatment regimen: results of a meta-analysis.
AB  - BACKGROUND: Terbinafine has been widely used with major success as a topical
      antifungal therapy for tinea pedis (athlete's foot). Its efficacy and safety have
      been validated in several clinical trials, which have demonstrated clinical
      efficacy for the drug after only 1 week of treatment when applied once daily, a
      reflection of the high fungicidal potency of the drug and its ability to form a
      depot in the upper skin layer. To improve patients' compliance further, a
      terbinafine-containing film-forming solution has been developed for single-dose
      therapy of athlete's foot. This novel formulation delivers terbinafine in high
      amounts and for a prolonged period of time into the skin, making one-shot
      treatment feasible. Over the past years there have been a variety of trials
      evaluating use of topical terbinafine addressing different pharmaceutical
      formulations, treatment durations, and application frequencies, but a detailed
      meta-analysis of these trials has not been conducted to date. OBJECTIVE: The
      present study is the first meta-analytic evaluation of the available data on the
      efficacy (clinical and mycologic cure rates) and safety (adverse events) of all
      topical forms of terbinafine for the treatment of tinea pedis. METHODS: An
      international, systematic literature search of 12 electronic databases (including
      MEDLINE, EMBASE, and Cochrane databases) using a pre-specified search strategy
      was conducted in March 2006. This meta-analysis included only randomized
      controlled trials in which terbinafine had been used for topical treatment of
      tinea pedis in comparison with placebo or an active control. Studies of all
      available topical formulations of terbinafine, frequencies of application, and
      durations of treatment were included. RESULTS: Of 100 identified articles
      published between 1990 and 2006, 19 met the criteria for analysis. These 19
      studies involved 2899 patients with clinical and mycologic diagnoses of tinea
      pedis (nine placebo-controlled trials and ten active-controlled trials). Efficacy
      analysis demonstrated that the mycologic cure rate was significantly superior
      with terbinafine compared with placebo (relative risk [RR] 3.17; p < 0.001). No
      significant differences in efficacy were found amongst different formulations of
      terbinafine, treatment durations, or frequencies of application. Comparable
      results were obtained with respect to clinical cure rate for terbinafine compared
      with placebo (RR 2.75; p < 0.001). Comparison of the efficacy of terbinafine
      versus active control indicated a nonsignificant difference in favor of
      terbinafine with regard to mycologic cure rate (RR 1.03; p = 0.423) and clinical
      cure rate (RR 1.09; p = 0.11). The median duration of treatment was also shorter
      with terbinafine (1 week) compared with active controls (2 weeks). Analysis of
      the placebo-controlled studies showed that there was no significant difference in
      the risk of adverse events with terbinafine compared with placebo (RR 1.34; p =
      0.34). Likewise, no significant differences in adverse events were found between
      terbinafine and active controls (RR 1.08; p = 0.72). CONCLUSION: Terbinafine is
      very well tolerated in any topical pharmaceutical formulation and also has high
      efficacy as a cure for tinea pedis, irrespective of type of pharmaceutical
      formulation, treatment duration, and frequency of application, including the
      recently established one-shot regimen. In addition, terbinafine has an apparently
      unique advantage over other antifungal agents with respect to the required
      duration of treatment for tinea pedis.

PMID- 18039019
TI  - Non-melanocytic benign skin tumors in children.
AB  - BACKGROUND: Dermatologists often attend children with benign skin tumors and
      cysts. The decision to perform dermatologic surgery in children may be difficult
      to make, especially in cases of benign tumors. OBJECTIVE: The objective of this
      study was to determine the nature of non-melanocytic benign skin tumors amenable
      to dermatologic surgery in children. METHODS: Histopathologic studies of skin
      tumors in children treated by our department between January 2004 and December
      2005 were studied. Malignant and melanocytic tumors were excluded. Age, sex, type
      of tumor, diagnostic category, site, size, reason for removal, type of
      anesthesia, and any other associated disorders were recorded. RESULTS: The
      records revealed that 121 patients presented 129 non-melanocytic benign skin
      tumors (73 in boys and 56 in girls). A total of 27 different anatomopathologic
      diagnoses were found. The most frequent was pilomatrixoma with 27 cases (20.9%),
      followed by infundibular cyst with 14 (10.9%), and molluscum contagiosum with 13
      (10.1%). Tumors were located on the head and neck (45.7%), trunk (34.1%), and
      limbs (20.1%). The most frequently affected age group was children aged 11-14
      years, which included 50 patients (38.8%). The main type of anesthesia used was
      local in 54.6% of the cases, sedation plus local anesthesia in 39.7%, and general
      anesthesia in 5.7%. The reasons that led to removal of the tumors were: increase
      in the size of the tumor (49%); various types of discomfort, such as severe
      itching or pain (30%); parental concern (4%); diagnostic uncertainty (16%); and
      esthetic reasons (1%). CONCLUSION: There is a wide diversity of non-melanocytic
      benign skin tumors in children, some of which require surgical treatment.
      Pilomatrixomas appear to be the most frequent benign tumors; there are also high
      frequencies of infundibular cysts, pyogenic granulomas, and viral tumors. Most
      can be removed under local anesthesia, with or without sedation.

PMID- 18039020
TI  - Comparative study of 2% sertaconazole solution and cream formulations in patients
      with tinea corporis, tinea pedis interdigitalis, or a corresponding candidosis.
AB  - BACKGROUND: Based on the results of numerous preclinical and clinical studies,
      sertaconazole can be considered a safe and effective drug for the treatment of
      fungal skin infections. OBJECTIVE: The objective of the study was to compare the
      efficacy of a solution containing 2% sertaconazole with the well established 2%
      sertaconazole cream formulation in patients with tinea corporis, tinea pedis
      interdigitalis, or a corresponding candidosis. METHODS: This was a prospective,
      open-label, randomized, controlled, parallel-group, multicenter, noninferiority
      therapy study. Patients received either sertaconazole solution or cream twice
      daily for 28 days. The full analysis set comprised 160 patients in the solution
      group and 153 patients in the cream group. The primary efficacy parameter was a
      combination of culture test result and total clinical score. Efficacy was defined
      by eradication of the pathogen and reduction of the total clinical score between
      pretreatment and the final visit. RESULTS: Efficacy was documented in 90.6% of
      patients using the solution and 88.9% of those using the cream (full analysis
      set). No adverse events occurred. CONCLUSION: Solution and cream formulations of
      2% sertaconazole applied for 28 days were associated with comparable efficacy and
      safety in the treatment of fungal skin infections.

PMID- 18039021
TI  - Multinodular cutaneous spread in neuroendocrine tumor of the breast : an unusual
      presentation.
AB  - Carcinoid tumors are the most common type of neuroendocrine tumors with an
      incidence of 1.5 per 100 000 of the population. Skin manifestations of carcinoid
      tumors include those associated with the carcinoid syndrome and sequelae from
      metastatic disease. Carcinoid tumors in the breast, which were first described in
      1977, are rare and may present either as primary or metastatic lesions. The
      existence of primary breast carcinoid tumors is controversial, however, and, if
      they do exist, would account for <1% of primary breast cancers. We report the
      case of a 76-year-old woman who presented to the M.D. Anderson Cancer Center with
      a long-standing history of a breast lump. Core biopsy of the mass and left
      axillary lymph node aspiration revealed neuroendocrine tumor of the breast, which
      stained positive for synaptophysin and chromogranin. Subsequently, the patient
      developed a left-sided pleural effusion, and a further work-up revealed
      metastases to the lung parenchyma and pleural space. Three years after her
      diagnosis, she complained of a persistent, erythematous thickening of skin over
      the surface of her left inferior breast, which had been present for 1 year. On
      examination, multiple erythematous grouped nodules arranged in an oval pattern
      were present. A punch biopsy from one of the nodules revealed invasive low-grade
      carcinoma with neuroendocrine features similar to those in her prior breast core
      biopsy. The tumor was seen to be infiltrating the dermis. This is a unique case
      of a neuroendocrine tumor of the breast with cutaneous spread. The number of
      reported cases of neuroendocrine tumors with cutaneous involvement remains small.

PMID- 18039022
TI  - Severe sporotrichoid fish tank granuloma following infliximab therapy.
AB  - Mycobacterium marinum is an atypical mycobacterium usually found in non
      chlorinated water. It rarely disseminates, except in the setting of a severely
      immunosuppressed patient, and usually follows a sporotrichotic type of
      distribution. We report the case of a 45-year-old man who had ankylosing
      spondylitis and was receiving infliximab and isoniazid for latent tuberculosis.
      The patient presented with a 5-month history of painful erythematous and
      suppurative nodules and abscesses on the right upper extremity. M. marinum was
      not isolated in cultures and histologic findings together with clinical
      examination provided evidence of sporotrichoid-like fish tank granuloma. The
      patient was treated with rifampin (rifampicin) and ethambutol for 8 months and
      responded satisfactorily while continuing to receive infliximab. In accordance
      with data in the published literature, isoniazid proved ineffective in preventing
      M. marinum infection in this patient. While mycobacterial complications of tumor
      necrosis factor-alpha (TNFalpha) inhibitor therapy are well established, our case
      appears to be the first reported instance of M. marinum infection in a patient
      taking infliximab. As anti-TNFalpha agents become increasingly used for a variety
      of conditions, awareness of the potential infectious complications associated
      with use of these agents will be vital for clinicians.

PMID- 18039023
TI  - Chronic bullous disease of childhood in a patient with acute lymphoblastic
      leukemia: possible induction by a drug.
AB  - Linear IgA disease is characterized by the presence of linear IgA deposits in the
      basement membrane zone of the skin, and circulating basement membrane zone
      antibodies are detected in 80% of cases. The disease occurs in both adults and
      children, and is designated adult linear IgA disease in the former and chronic
      bullous disease of childhood (CBDC) in the latter. We describe a 5-year-old boy
      with acute lymphoblastic leukemia in remission, in whom CBDC developed after
      treatment with trimethoprim/sulfamethoxazole (cotrimoxazole). To our knowledge,
      this is the first reported case of possible drug-induced CBDC.

PMID- 18039024
TI  - Asymptomatic papules and tumors of the face, neck, and trunk combined with renal,
      intestinal, and prostatic malignancies.

PMID- 18039025
TI  - Phenotypic mutation rates and the abundance of abnormal proteins in yeast.
AB  - Phenotypic mutations are errors that occur during protein synthesis. These errors
      lead to amino acid substitutions that give rise to abnormal proteins. Experiments
      suggest that such errors are quite common. We present a model to study the effect
      of phenotypic mutation rates on the amount of abnormal proteins in a cell. In our
      model, genes are regulated to synthesize a certain number of functional proteins.
      During this process, depending on the phenotypic mutation rate, abnormal proteins
      are generated. We use data on protein length and abundance in Saccharomyces
      cerevisiae to parametrize our model. We calculate that for small phenotypic
      mutation rates most abnormal proteins originate from highly expressed genes that
      are on average nearly twice as large as the average yeast protein. For phenotypic
      mutation rates much above 5 x 10(-4), the error-free synthesis of large proteins
      is nearly impossible and lowly expressed, very large proteins contribute more and
      more to the amount of abnormal proteins in a cell. This fact leads to a steep
      increase of the amount of abnormal proteins for phenotypic mutation rates above 5
      x 10(-4). Simulations show that this property leads to an upper limit for the
      phenotypic mutation rate of approximately 2 x 10(-3) even if the costs for
      abnormal proteins are extremely low. We also consider the adaptation of
      individual proteins. Individual genes/proteins can decrease their phenotypic
      mutation rate by using preferred codons or by increasing their robustness against
      amino acid substitutions. We discuss the similarities and differences between the
      two mechanisms and show that they can only slow down but not prevent the rapid
      increase of the amount of abnormal proteins. Our work allows us to estimate the
      phenotypic mutation rate based on data on the fraction of abnormal proteins. For
      S. cerevisiae, we predict that the value for the phenotypic mutation rate is
      between 2 x 10(-4) and 6 x 10(-4).

PMID- 18039026
TI  - Where have all the interactions gone? Estimating the coverage of two-hybrid
      protein interaction maps.
AB  - Yeast two-hybrid screens are an important method for mapping pairwise physical
      interactions between proteins. The fraction of interactions detected in
      independent screens can be very small, and an outstanding challenge is to
      determine the reason for the low overlap. Low overlap can arise from either a
      high false-discovery rate (interaction sets have low overlap because each set is
      contaminated by a large number of stochastic false-positive interactions) or a
      high false-negative rate (interaction sets have low overlap because each misses
      many true interactions). We extend capture-recapture theory to provide the first
      unified model for false-positive and false-negative rates for two-hybrid screens.
      Analysis of yeast, worm, and fly data indicates that 25% to 45% of the reported
      interactions are likely false positives. Membrane proteins have higher false
      discovery rates on average, and signal transduction proteins have lower rates.
      The overall false-negative rate ranges from 75% for worm to 90% for fly, which
      arises from a roughly 50% false-negative rate due to statistical undersampling
      and a 55% to 85% false-negative rate due to proteins that appear to be
      systematically lost from the assays. Finally, statistical model selection
      conclusively rejects the Erdos-Renyi network model in favor of the power law
      model for yeast and the truncated power law for worm and fly degree
      distributions. Much as genome sequencing coverage estimates were essential for
      planning the human genome sequencing project, the coverage estimates developed
      here will be valuable for guiding future proteomic screens. All software and
      datasets are available in and , -, and -, and are also available from our Web
      site, http://www.baderzone.org.

PMID- 18039027
TI  - An evolutionary-network model reveals stratified interactions in the V3 loop of
      the HIV-1 envelope.
AB  - The third variable loop (V3) of the human immunodeficiency virus type 1 (HIV-1)
      envelope is a principal determinant of antibody neutralization and progression to
      AIDS. Although it is undoubtedly an important target for vaccine research,
      extensive genetic variation in V3 remains an obstacle to the development of an
      effective vaccine. Comparative methods that exploit the abundance of sequence
      data can detect interactions between residues of rapidly evolving proteins such
      as the HIV-1 envelope, revealing biological constraints on their variability.
      However, previous studies have relied implicitly on two biologically unrealistic
      assumptions: (1) that founder effects in the evolutionary history of the
      sequences can be ignored, and; (2) that statistical associations between residues
      occur exclusively in pairs. We show that comparative methods that neglect the
      evolutionary history of extant sequences are susceptible to a high rate of false
      positives (20%-40%). Therefore, we propose a new method to detect interactions
      that relaxes both of these assumptions. First, we reconstruct the evolutionary
      history of extant sequences by maximum likelihood, shifting focus from extant
      sequence variation to the underlying substitution events. Second, we analyze the
      joint distribution of substitution events among positions in the sequence as a
      Bayesian graphical model, in which each branch in the phylogeny is a unit of
      observation. We perform extensive validation of our models using both simulations
      and a control case of known interactions in HIV-1 protease, and apply this method
      to detect interactions within V3 from a sample of 1,154 HIV-1 envelope sequences.
      Our method greatly reduces the number of false positives due to founder effects,
      while capturing several higher-order interactions among V3 residues. By mapping
      these interactions to a structural model of the V3 loop, we find that the loop is
      stratified into distinct evolutionary clusters. We extend our model to detect
      interactions between the V3 and C4 domains of the HIV-1 envelope, and account for
      the uncertainty in mapping substitutions to the tree with a parametric bootstrap.

PMID- 18039028
TI  - A universal mechanism ties genotype to phenotype in trinucleotide diseases.
AB  - Trinucleotide hereditary diseases such as Huntington disease and Friedreich
      ataxia are cureless diseases associated with inheriting an abnormally large
      number of DNA trinucleotide repeats in a gene. The genes associated with
      different diseases are unrelated and harbor a trinucleotide repeat in different
      functional regions; therefore, it is striking that many of these diseases have
      similar correlations between their genotype, namely the number of inherited
      repeats and age of onset and progression phenotype. These correlations remain
      unexplained despite more than a decade of research. Although mechanisms have been
      proposed for several trinucleotide diseases, none of the proposals, being disease
      specific, can account for the commonalities among these diseases. Here, we
      propose a universal mechanism in which length-dependent somatic repeat expansion
      occurs during the patient's lifetime toward a pathological threshold. Our
      mechanism uniformly explains for the first time to our knowledge the genotype
      phenotype correlations common to trinucleotide disease and is well-supported by
      both experimental and clinical data. In addition, mathematical analysis of the
      mechanism provides simple explanations to a wide range of phenomena such as the
      exponential decrease of the age-of-onset curve, similar onset but faster
      progression in patients with Huntington disease with homozygous versus
      heterozygous mutation, and correlation of age of onset with length of the short
      allele but not with the long allele in Friedreich ataxia. If our proposed
      universal mechanism proves to be the core component of the actual mechanisms of
      specific trinucleotide diseases, it would open the search for a uniform treatment
      for all these diseases, possibly by delaying the somatic expansion process.

PMID- 18039029
TI  - A model of bacterial intestinal infections in Drosophila melanogaster.
AB  - Serratia marcescens is an entomopathogenic bacterium that opportunistically
      infects a wide range of hosts, including humans. In a model of septic injury, if
      directly introduced into the body cavity of Drosophila, this pathogen is
      insensitive to the host's systemic immune response and kills flies in a day. We
      find that S. marcescens resistance to the Drosophila immune deficiency (imd)
      mediated humoral response requires the bacterial lipopolysaccharide O-antigen. If
      ingested by Drosophila, bacteria cross the gut and penetrate the body cavity.
      During this passage, the bacteria can be observed within the cells of the
      intestinal epithelium. In such an oral infection model, the flies succumb to
      infection only after 6 days. We demonstrate that two complementary host defense
      mechanisms act together against such food-borne infection: an antimicrobial
      response in the intestine that is regulated by the imd pathway and phagocytosis
      by hemocytes of bacteria that have escaped into the hemolymph. Interestingly,
      bacteria present in the hemolymph elicit a systemic immune response only when
      phagocytosis is blocked. Our observations support a model wherein peptidoglycan
      fragments released during bacterial growth activate the imd pathway and do not
      back a proposed role for phagocytosis in the immune activation of the fat body.
      Thanks to the genetic tools available in both host and pathogen, the molecular
      dissection of the interactions between S. marcescens and Drosophila will provide
      a useful paradigm for deciphering intestinal pathogenesis.

PMID- 18039030
TI  - Theme and variations in the evolutionary pathways to virulence of an RNA plant
      virus species.
AB  - The diversity of a highly variable RNA plant virus was considered to determine
      the range of virulence substitutions, the evolutionary pathways to virulence, and
      whether intraspecific diversity modulates virulence pathways and propensity. In
      all, 114 isolates representative of the genetic and geographic diversity of Rice
      yellow mottle virus (RYMV) in Africa were inoculated to several cultivars with
      eIF(iso)4G-mediated Rymv1-2 resistance. Altogether, 41 virulent variants
      generated from ten wild isolates were analyzed. Nonconservative amino acid
      replacements at five positions located within a stretch of 15 codons in the
      central region of the 79-aa-long protein VPg were associated with virulence.
      Virulence substitutions were fixed predominantly at codon 48 in most strains,
      whatever the host genetic background or the experimental conditions. There were
      one major and two isolate-specific mutational pathways conferring virulence at
      codon 48. In the prevalent mutational pathway I, arginine (AGA) was successively
      displaced by glycine (GGA) and glutamic acid (GAA). Substitutions in the other
      virulence codons were displaced when E48 was fixed. In the isolate-specific
      mutational pathway II, isoleucine (ATA) emerged and often later coexisted with
      valine (GTA). In mutational pathway III, arginine, with the specific S2/S3 strain
      codon usage AGG, was displaced by tryptophane (TGG). Mutational pathway I never
      arose in the widely spread West African S2/S3 strain because G48 was not
      infectious in the S2/S3 genetic context. Strain S2/S3 least frequently overcame
      resistance, whereas two geographically localized variants of the strain S4 had a
      high propensity to virulence. Codons 49 and 26 of the VPg, under diversifying
      selection, are candidate positions in modulating the genetic barriers to
      virulence. The theme and variations in the evolutionary pathways to virulence of
      RYMV illustrates the extent of parallel evolution within a highly variable RNA
      plant virus species.

PMID- 18039032
TI  - Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed
      mothers.
AB  - The long-term health outcome of prenatal exposure to arsenic has been associated
      with increased mortality in human populations. In this study, the extent to which
      maternal arsenic exposure impacts gene expression in the newborn was addressed.
      We monitored gene expression profiles in a population of newborns whose mothers
      experienced varying levels of arsenic exposure during pregnancy. Through the
      application of machine learning-based two-class prediction algorithms, we
      identified expression signatures from babies born to arsenic-unexposed and 
      exposed mothers that were highly predictive of prenatal arsenic exposure in a
      subsequent test population. Furthermore, 11 transcripts were identified that
      captured the maximal predictive capacity to classify prenatal arsenic exposure.
      Network analysis of the arsenic-modulated transcripts identified the activation
      of extensive molecular networks that are indicative of stress, inflammation,
      metal exposure, and apoptosis in the newborn. Exposure to arsenic is an important
      health hazard both in the United States and around the world, and is associated
      with increased risk for several types of cancer and other chronic diseases. These
      studies clearly demonstrate the robust impact of a mother's arsenic consumption
      on fetal gene expression as evidenced by transcript levels in newborn cord blood.

PMID- 18039031
TI  - Genetic variation and population structure in native Americans.
AB  - We examined genetic diversity and population structure in the American landmass
      using 678 autosomal microsatellite markers genotyped in 422 individuals
      representing 24 Native American populations sampled from North, Central, and
      South America. These data were analyzed jointly with similar data available in 54
      other indigenous populations worldwide, including an additional five Native
      American groups. The Native American populations have lower genetic diversity and
      greater differentiation than populations from other continental regions. We
      observe gradients both of decreasing genetic diversity as a function of
      geographic distance from the Bering Strait and of decreasing genetic similarity
      to Siberians--signals of the southward dispersal of human populations from the
      northwestern tip of the Americas. We also observe evidence of: (1) a higher level
      of diversity and lower level of population structure in western South America
      compared to eastern South America, (2) a relative lack of differentiation between
      Mesoamerican and Andean populations, (3) a scenario in which coastal routes were
      easier for migrating peoples to traverse in comparison with inland routes, and
      (4) a partial agreement on a local scale between genetic similarity and the
      linguistic classification of populations. These findings offer new insights into
      the process of population dispersal and differentiation during the peopling of
      the Americas.

PMID- 18039033
TI  - Extragenic accumulation of RNA polymerase II enhances transcription by RNA
      polymerase III.
AB  - Recent genomic data indicate that RNA polymerase II (Pol II) function extends
      beyond conventional transcription of primarily protein-coding genes. Among the
      five snRNAs required for pre-mRNA splicing, only the U6 snRNA is synthesized by
      RNA polymerase III (Pol III). Here we address the question of how Pol II
      coordinates the expression of spliceosome components, including U6. We used
      chromatin immunoprecipitation (ChIP) and high-resolution mapping by PCR to
      localize both Pol II and Pol III to snRNA gene regions. We report the surprising
      finding that Pol II is highly concentrated approximately 300 bp upstream of all
      five active human U6 genes in vivo. The U6 snRNA, an essential component of the
      spliceosome, is synthesized by Pol III, whereas all other spliceosomal snRNAs are
      Pol II transcripts. Accordingly, U6 transcripts were terminated in a Pol III
      specific manner, and Pol III localized to the transcribed gene regions. However,
      synthesis of both U6 and U2 snRNAs was alpha-amanitin-sensitive, indicating a
      requirement for Pol II activity in the expression of both snRNAs. Moreover, both
      Pol II and histone tail acetylation marks were lost from U6 promoters upon alpha
      amanitin treatment. The results indicate that Pol II is concentrated at specific
      genomic regions from which it can regulate Pol III activity by a general
      mechanism. Consequently, Pol II coordinates expression of all RNA and protein
      components of the spliceosome.

PMID- 18039035
TI  - The detection of fear-relevant stimuli: are guns noticed as quickly as snakes?
AB  - Potentially dangerous stimuli are important contenders for the capture of visual
      spatial attention, and it has been suggested that an evolved fear module is
      preferentially activated by stimuli that are fear relevant in a phylogenetic
      sense (e.g., snakes, spiders, angry faces). In this study, a visual search task
      was used to test this hypothesis by directly contrasting phylogenetically
      (snakes) and ontogenetically (guns) fear-relevant stimuli. Results showed that
      the modern threat was detected as efficiently as the more ancient threat. Thus,
      both guns and snakes attracted attention more effectively than neutral stimuli
      (flowers, mushrooms, and toasters). These results support a threat superiority
      effect but not one that is preferentially accessed by threat-related stimuli of
      phylogenetic origin. The results are consistent with the view that faster
      detection of threat in visual search tasks may be more accurately characterized
      as relevance superiority effects rather than as threat superiority effects.

PMID- 18039036
TI  - How emotional auditory stimuli modulate time perception.
AB  - Emotional and neutral sounds rated for valence and arousal were used to
      investigate the influence of emotions on timing in reproduction and verbal
      estimation tasks with durations from 2 s to 6 s. Results revealed an effect of
      emotion on temporal judgment, with emotional stimuli judged to be longer than
      neutral ones for a similar arousal level. Within scalar expectancy theory (J.
      Gibbon, R. Church, & W. Meck, 1984), this suggests that emotion-induced
      activation generates an increase in pacemaker rate, leading to a longer perceived
      duration. A further exploration of self-assessed emotional dimensions showed an
      effect of valence and arousal. Negative sounds were judged to be longer than
      positive ones, indicating that negative stimuli generate a greater increase of
      activation. High-arousing stimuli were perceived to be shorter than low-arousing
      ones. Consistent with attentional models of timing, this seems to reflect a
      decrease of attention devoted to time, leading to a shorter perceived duration.
      These effects, robust across the 2 tasks, are limited to short intervals and
      overall suggest that both activation and attentional processes modulate the
      timing of emotional events.

PMID- 18039034
TI  - Genomic and functional studies of Drosophila sex hierarchy regulated gene
      expression in adult head and nervous system tissues.
AB  - The Drosophila sex determination hierarchy controls all aspects of somatic sexual
      differentiation, including sex-specific differences in adult morphology and
      behavior. To gain insight into the molecular-genetic specification of
      reproductive behaviors and physiology, we identified genes expressed in the adult
      head and central nervous system that are regulated downstream of sex-specific
      transcription factors encoded by doublesex (dsx) and fruitless (fru). We used a
      microarray approach and identified 54 genes regulated downstream of dsx.
      Furthermore, based on these expression studies we identified new modes of DSX
      regulated gene expression. We also identified 90 and 26 genes regulated in the
      adult head and central nervous system tissues, respectively, downstream of the
      sex-specific transcription factors encoded by fru. In addition, we present
      molecular-genetic analyses of two genes identified in our studies, calphotin
      (cpn) and defective proboscis extension response (dpr), and begin to describe
      their functional roles in male behaviors. We show that dpr and dpr-expressing
      cells are required for the proper timing of male courtship behaviors.

PMID- 18039037
TI  - Aging and goal-directed emotional attention: distraction reverses emotional
      biases.
AB  - Previous findings reveal that older adults favor positive over negative stimuli
      in both memory and attention (for a review, see Mather & Carstensen, 2005). This
      study used eye tracking to investigate the role of cognitive control in older
      adults' selective visual attention. Younger and older adults viewed emotional
      neutral and emotional-emotional pairs of faces and pictures while their gaze
      patterns were recorded under full or divided attention conditions. Replicating
      previous eye-tracking findings, older adults allocated less of their visual
      attention to negative stimuli in negative-neutral stimulus pairings in the full
      attention condition than younger adults did. However, as predicted by a cognitive
      control-based account of the positivity effect in older adults' information
      processing tendencies (Mather & Knight, 2005), older adults' tendency to avoid
      negative stimuli was reversed in the divided attention condition. Compared with
      younger adults, older adults' limited attentional resources were more likely to
      be drawn to negative stimuli when they were distracted. These findings indicate
      that emotional goals can have unintended consequences when cognitive control
      mechanisms are not fully available.

PMID- 18039038
TI  - Clearing the mind: a working memory model of distraction from negative mood.
AB  - The present research examined whether and how loading working memory can
      attenuate negative mood. In three experiments, participants were exposed to
      neutral, weakly negative, or strongly negative pictures followed by a task and a
      mood scale. Working memory demands were varied by manipulating task presence
      (Study 1), complexity (Study 2), and predictability (Study 3). Participants in
      all three experiments reported less negative moods in negative trials with high
      compared to low working memory demand. Working memory demands did not affect mood
      in the neutral trials. When working memory demands were high, participants no
      longer reported more negative moods in response to strongly negative pictures
      than to weakly negative pictures. These findings suggest that loading working
      memory prevents mood-congruent processing, and thereby promotes distraction from
      negative moods.

PMID- 18039039
TI  - Processing of observed pupil size modulates perception of sadness and predicts
      empathy.
AB  - Facial autonomic responses may contribute to emotional communication and reveal
      individual affective style. In this study, the authors examined how observed
      pupillary size modulates processing of facial expression, extending the finding
      that incidentally perceived pupils influence ratings of sadness but not those of
      happy, angry, or neutral facial expressions. Healthy subjects rated the valence
      and arousal of photographs depicting facial muscular expressions of sadness,
      surprise, fear, and disgust. Pupil sizes within the stimuli were experimentally
      manipulated. Subjects themselves were scored with an empathy questionnaire.
      Diminishing pupil size linearly enhanced intensity and valence judgments of sad
      expressions (but not fear, surprise, or disgust). At debriefing, subjects were
      unaware of differences in pupil size across stimuli. These observations
      complement an earlier study showing that pupil size directly influences
      processing of sadness but not other basic emotional facial expressions.
      Furthermore, across subjects, the degree to which pupil size influenced sadness
      processing correlated with individual differences in empathy score. Together,
      these data demonstrate a central role of sadness processing in empathetic emotion
      and highlight the salience of implicit autonomic signals in affective
      communication.

PMID- 18039040
TI  - Facial dynamics as indicators of trustworthiness and cooperative behavior.
AB  - Detecting cooperative partners in situations that have financial stakes is
      crucial to successful social exchange. The authors tested whether humans are
      sensitive to subtle facial dynamics of counterparts when deciding whether to
      trust and cooperate. Participants played a 2-person trust game before which the
      facial dynamics of the other player were manipulated using brief (<6 s) but
      highly realistic facial animations. Results showed that facial dynamics
      significantly influenced participants' (a) choice of with whom to play the game
      and (b) decisions to cooperate. It was also found that inferences about the other
      player's trustworthiness mediated these effects of facial dynamics on cooperative
      behavior.

PMID- 18039042
TI  - Judgments of emotion from spontaneous facial expressions of New Guineans.
AB  - The claim that specific discrete emotions can be universally recognized from
      human facial expressions is based mainly on the study of expressions that were
      posed. The current study (N=50) examined recognition of emotion from 20
      spontaneous expressions from Papua New Guinea photographed, coded, and labeled by
      P. Ekman (1980). For the 16 faces with a single predicted label, endorsement of
      that label ranged from 4.2% to 45.8% (mean 24.2%). For 4 faces with 2 predicted
      labels (blends), endorsement of one or the other ranged from 6.3% to 66.6% (mean
      38.8%). Of the 24 labels Ekman predicted, 11 were endorsed at an above-chance
      level, and 13 were not. Spontaneous expressions do not achieve the level of
      recognition achieved by posed expressions.

PMID- 18039043
TI  - Functional magnetic resonance imaging responses relate to differences in real
      world social experience.
AB  - Although neuroimaging techniques have proven powerful in assessing neural
      responses, little is known about whether scanner-based neural activity relates to
      real-world psychological experience. A joint functional magnetic resonance
      imaging (fMRI)/experience-sampling study investigated whether individual
      differences in neurocognitive reactivity to scanner-based social rejection
      related to: (a) moment-to-moment feelings of social rejection during real-world
      social interactions ("momentary social distress") and (b) the extent to which
      these momentary feelings corresponded with end-of-day global assessments of
      social disconnection ("end-of-day social disconnection"). Individuals who showed
      greater activity in regions associated with affective and pain processing (dorsal
      anterior cingulate cortex, amygdala, periaqueductal gray) during scanner-based
      social rejection reported feeling greater momentary social distress during their
      daily social interactions. In contrast, individuals who showed greater activity
      in regions associated with memory and self-referential memory encoding
      (hippocampus, medial prefrontal cortex) showed a stronger correspondence between
      momentary social distress and end-of-day social disconnection, such that greater
      momentary social distress was associated with greater end-of-day social
      disconnection. These findings complement previous work showing a dissociation
      between momentary and retrospective reports of affect and suggest that these
      processes rely on dissociable neural systems.

PMID- 18039045
TI  - Under what conditions can human affective conditioning occur without contingency
      awareness? Test of the evaluative conditioning paradigm.
AB  - The role of conscious cognitive processes in human affective conditioning remains
      controversial, with several theories arguing that such conditioning can occur
      without awareness of the conditioned stimulus (CS)-unconditioned stimulus (UCS)
      contingency. One specific type of affective conditioning in which unaware
      conditioning is said to occur is "evaluative conditioning." The present
      experiment tested the role of contingency awareness by embedding an evaluative
      conditioning paradigm in a distracting masking task while obtaining, in addition
      to subjective ratings of affect, both psychophysiological (skin conductance and
      startle eyeblink) and indirect behavioral (affective priming) measures of
      conditioning, along with a trial-by-trial measure of awareness from 55 college
      student participants. Aware participants showed conditioning with all of the
      measures; unaware participants failed to show conditioning with all measures. The
      behavioral, neurophysiological, and therapeutic implications of these findings
      are discussed.

PMID- 18039046
TI  - Brain activation while forming memories of fearful and neutral faces in women and
      men.
AB  - Event-related functional MRI (fMRI) was used to assess brain activity during
      encoding of fearful and neutral faces in 12 women and 12 men. In a subsequent
      memory analysis, the authors separated successful from unsuccessful encoding of
      both types of faces, based on whether they were remembered or forgotten in a
      later recognition memory test. Overall, women and men recruited overlapping
      neural circuitries. Both sexes activated right-sided medial-temporal regions
      during successful encoding of fearful faces. Successful encoding of neutral faces
      was associated with left-sided lateral prefrontal and right-sided superior
      frontal activation in both sexes. In women, relatively greater encoding related
      activity for neutral faces was seen in the superior parietal and parahippocampal
      cortices. By contrast, men activated the left and right superior/middle frontal
      cortex more than women during successful encoding of the same neutral faces.
      These findings suggest that women and men use similar neural networks to encode
      facial information, with only subtle sex differences observed for neutral faces.

PMID- 18039047
TI  - Emotions over time: synchronicity and development of subjective, physiological,
      and facial affective reactions to music.
AB  - Most people are able to identify basic emotions expressed in music and experience
      affective reactions to music. But does music generally induce emotion? Does it
      elicit subjective feelings, physiological arousal, and motor reactions reliably
      in different individuals? In this interdisciplinary study, measurement of skin
      conductance, facial muscle activity, and self-monitoring were synchronized with
      musical stimuli. A group of 38 participants listened to classical, rock, and pop
      music and reported their feelings in a two-dimensional emotion space during
      listening. The first entrance of a solo voice or choir and the beginning of new
      sections were found to elicit interindividual changes in subjective feelings and
      physiological arousal. Quincy Jones' "Bossa Nova" motivated movement and laughing
      in more than half of the participants. Bodily reactions such as "goose bumps" and
      "shivers" could be stimulated by the "Tuba Mirum" from Mozart's Requiem in 7 of
      38 participants. In addition, the authors repeated the experiment seven times
      with one participant to examine intraindividual stability of effects. This
      exploratory combination of approaches throws a new light on the astonishing
      complexity of affective music listening.

PMID- 18039048
TI  - The prototypical pride expression: development of a nonverbal behavior coding
      system.
AB  - This research provides a systematic analysis of the nonverbal expression of
      pride. Study 1 manipulated behavioral movements relevant to pride (e.g., expanded
      posture and head tilt) to identify the most prototypical pride expression and
      determine the specific components that are necessary and sufficient for reliable
      recognition. Studies 2 and 3 tested whether the 2 conceptually and empirically
      distinct facets of pride ("authentic" and "hubristic"; J. L. Tracy & R. W.
      Robins, 2007a) are associated with distinct nonverbal expressions. Results showed
      that neither the prototypical pride expression nor several recognizable variants
      were differentially associated with either facet, suggesting that for the most
      part, authentic and hubristic pride share the same signal. Together these studies
      indicate that pride can be reliably assessed from nonverbal behaviors. In the
      Appendix, the authors provide guidelines for a pride behavioral coding scheme,
      akin to the Emotion Facial Action Coding System (EMFACS; P. Ekman & E. Rosenberg,
      1997) for assessing "basic" emotions from observable nonverbal behaviors.

PMID- 18039049
TI  - The influence of sad mood on cognition.
AB  - Neuroimaging has identified an overlapping network of brain regions whose
      activity is modulated by mood and cognition. Studies of depressed individuals
      have shown changes in perception, attention, memory, and executive functions.
      This suggests that mood has a pervasive effect on cognition. Direct evidence of
      the effect of sad mood on cognition is surprisingly limited, however. Published
      studies have generally addressed a single cognitive ability per study because the
      fleeting nature of laboratory-induced mood precludes extended testing, and robust
      findings are limited to mood effects on memory for emotional stimuli. In this
      study, sad mood was induced and prolonged, enabling the effects of mood to be
      assessed for an array of abilities, including those that share neural substrates
      with sad mood and those affected by depression. Sad mood affected memory for
      emotional words and facial emotion recognition, but not the other processes
      measured, with a significant nonuniformity of effect over tasks. These results
      are consistent with circumscribed effects of sad mood on certain emotion-related
      cognitive processes, but not on cognition more generally.

PMID- 18039051
TI  - "Just stop thinking about it": effects of emotional disengagement on children's
      memory for educational material.
AB  - Children regulate negative emotions in a variety of ways. Emotion education
      programs typically discourage emotional disengagement and encourage emotional
      engagement or "working through" negative emotions. The authors examined the
      effects of emotional disengagement and engagement on children's memory for
      educational material. Children averaging 7 or 10 years of age (N=200) watched
      either a sad or an emotionally neutral film and were then instructed to
      emotionally disengage, instructed to engage in problem solving concerning their
      emotion, or received no emotion regulation instructions. All children then
      watched and were asked to recall the details of an emotionally neutral
      educational film. Children instructed to disengage remembered the educational
      film better than children instructed to work through their feelings or children
      who received no emotion regulation instructions. Although past research has
      indicated that specific forms of emotional disengagement can impair memory for
      emotionally relevant events, the current findings suggest that disengagement is a
      useful short-term strategy for regulating mild negative emotion in educational
      settings.

PMID- 18039052
TI  - Context matters: the benefits and costs of expressing positive emotion among
      survivors of childhood sexual abuse.
AB  - Positive emotions promote adjustment to aversive life events. However,
      evolutionary theory and empirical research on trauma disclosure suggest that in
      the context of stigmatized events, expressing positive emotions might incur
      social costs. To test this thesis, the authors coded genuine (Duchenne) smiling
      and laughter and also non-Duchenne smiling from videotapes of late-adolescent and
      young adult women, approximately half with documented histories of childhood
      sexual abuse (CSA), as they described the most distressing event of their lives.
      Consistent with previous studies, genuine positive emotional expression was
      generally associated with better social adjustment two years later. However, as
      anticipated, CSA survivors who expressed positive emotion in the context of
      describing a past CSA experience had poorer long-term social adjustment, whereas
      CSA survivors who expressed positive emotion while describing a nonabuse
      experience had improved social adjustment. These findings suggest that the
      benefits of positive emotional expression may often be context specific.

PMID- 18039053
TI  - Physical abuse amplifies attention to threat and increases anxiety in children.
AB  - Two experiments using event-related potentials (ERPs) examined the extent to
      which early traumatic experiences affect children's ability to regulate voluntary
      and involuntary attention to threat. The authors presented physically abused and
      nonabused comparison children with conflicting auditory and visual emotion cues,
      posed by children's mothers or a stranger, to examine the effect of emotion,
      modality, and poser familiarity on attention regulation. Relative to controls,
      abused children overattended to task-relevant visual and auditory anger cues.
      They also attended more to task-irrelevant auditory anger cues. Furthermore, the
      degree of attention allocated to threat statistically mediated the relationship
      between physical abuse and child-reported anxiety. These findings indicate that
      extreme emotional experiences may promote vulnerability for anxiety by
      influencing the development of attention regulation abilities.

PMID- 18039054
TI  - Anger, disgust, and presumption of harm as reactions to taboo-breaking behaviors.
AB  - Three experiments investigated the relationship between the presumption of harm
      in harmfree violations of creatural norms (taboos) and the moral emotions of
      anger and disgust. In Experiment 1, participants made a presumption of harm to
      others from taboo violations, even in conditions described as harmless and not
      involving other people; this presumption was predicted by anger and not disgust.
      Experiment 2 manipulated taboo violation and included a cognitive load task to
      clarify the post hoc nature of presumption of harm. Experiment 3 was similar but
      more accurately measured presumed harm. In Experiments 2 and 3, only without load
      was symbolic harm presumed, indicating its post hoc function to justify moral
      anger, which was not affected by load. In general, manipulations of harmfulness
      to others predicted moral anger better than moral disgust, whereas manipulations
      of taboo predicted disgust better. The presumption of harm was found on measures
      of symbolic rather than actual harm when a choice existed. These studies clarify
      understanding of the relationship between emotions and their justification when
      people consider victimless, offensive acts.

PMID- 18039055
TI  - A bumpy train ride: a field experiment on insult, honor, and emotional reactions.
AB  - The present research examined the relationship between adherence to honor norms
      and emotional reactions after an insult. Participants were 42 Dutch male train
      travelers, half of whom were insulted by a confederate who bumped into the
      participant and made a degrading remark. Compared with insulted participants with
      a weak adherence to honor norms, insulted participants with a strong adherence to
      honor norms were (a) more angry, (b) less joyful, (c) less fearful, and (d) less
      resigned. Moreover, insulted participants with a strong adherence to honor norms
      perceived more anger in subsequent stimuli than not-insulted participants with a
      strong adherence to these norms. The present findings support a direct
      relationship among insult, adherence to honor norms, and emotional reactions.

PMID- 18039057
TI  - Incidental sadness biases social economic decisions in the Ultimatum Game.
AB  - Recent dual-process models of decision making have suggested that emotion plays
      an important role in decision making; however, the impact of incidental moods
      (i.e., emotions unrelated to the immediate situation) on decisions remains poorly
      explored. This question was investigated by inducing 2 basic emotional states
      (amusement or sadness) that were compared with a neutral-emotion control group.
      Decision making was assessed with a well-studied social task, the Ultimatum Game.
      In this task, participants had to make decisions to either accept or reject
      monetary offers from other players, offers that varied in their degree of
      unfairness. Emotion was induced with short movie clips. Induced sadness
      interacted with offer fairness, with higher sadness resulting in lower acceptance
      rates of unfair offers. Induced amusement was not associated with any significant
      biases in decision making. These results demonstrate that even subtle incidental
      moods can play an important role in biasing decision making. Implications of
      these results in regards to the emotion, cognitive neuroscience, and clinical
      literatures are discussed.

PMID- 18039058
TI  - Fearful expressions gain preferential access to awareness during continuous flash
      suppression.
AB  - Rapid evaluation of ecologically relevant stimuli may lead to their preferential
      access to awareness. Continuous flash suppression allows assessment of affective
      processing under conditions in which stimuli have been rendered invisible due to
      the strongly suppressive nature of dynamic noise relative to static images. The
      authors investigated whether fearful expressions emerge from suppression into
      awareness more quickly than images of neutral or happy expressions. Fearful faces
      were consistently detected faster than neutral or happy faces. Responses to
      inverted faces were slower than those to upright faces but showed the same effect
      of emotional expression, suggesting that some key feature or features in the
      inverted faces remained salient. When using stimuli solely representing the eyes,
      a similar bias for detecting fear emerged, implicating the importance of
      information from the eyes in the preconscious processing of fear expressions.

PMID- 18039060
TI  - Stress, menopause and vulnerability for psychiatric illness.

PMID- 18039061
TI  - Treatment of vasomotor symptoms in the menopausal transition and
      postmenopausally: psychiatric comorbidity.
AB  - This article aims to educate the nonpsychiatric as well as the psychiatric
      clinician on the impact of vasomotor symptoms in women with comorbid psychiatric
      problems and the challenges of treating vasomotor symptoms in these women. The
      pathophysiology, prevalence and common risk factors associated with disturbing
      hot flashes in the menopausal transition are reviewed. Hormonal, nonhormonal and
      behavioral treatment options of vasomotor symptoms for these women are discussed.
      Special pharmacokinetic implications for hormonal treatment of those women on
      anticonvulsant medications for the treatment of their mood disorders, on
      tamoxifen and/or with high or low sex hormone-binding globulin are examined. An
      in-depth discussion of mood and the menopausal transition, theoretical mechanisms
      for mood problems with the symptomatic menopause and the impact of stress on the
      symptomatic menopause are found elsewhere in this clinical review series on
      psychiatric illness, stress and the symptomatic menopause.

PMID- 18039062
TI  - Assessment and treatment for insomnia and fatigue in the symptomatic menopausal
      woman with psychiatric comorbidity.
AB  - Studies and treatments for the symptomatic menopausal woman with sleep complaints
      have been reviewed elsewhere. This article, as part of the clinical review series
      on the comorbid symptomatic menopausal woman, aims to examine the evidence for
      diagnosis and treatment of women who present with distressing sleep symptoms that
      they attribute to menopause. The etiology of these symptoms may be a psychiatric
      disorder, a pre- or co-existing problem with sleep, or a dynamic interaction
      among one of these and/or a symptomatic menopause. The relationship between sleep
      disturbance and cognitive complaints, mood problems, fatigue and low energy will
      be reviewed. The new research on sleep, clinical consequences of insomnia of
      various types, the impact of sleep disturbance on morbidity and functioning--in
      the context of the midlife woman in the menopausal transition--will be explored
      along with the evidence for different treatment strategies for these sleep
      problems.

PMID- 18039063
TI  - Arthralgias, bodily aches and pains and somatic complaints in midlife women:
      etiology, pathophysiology and differential diagnosis.
AB  - Somatic symptoms characterized by arthralgias, bodily aches and pains,
      musculoskeletal pain and joint pain have been investigated in a number of
      menopause and depression studies. Although depression is one of the most common
      causes of bodily aches and pains, and arthralgias, these same symptoms are also
      commonly associated with a natural menopause, surgical menopause and menopause
      induced by chemotherapy in breast cancer treatment. Somatic symptoms in the
      absence of definitive medical diagnoses result in these patients receiving
      various diagnoses and labels--'medically unexplained symptoms', 'worried well',
      as well as various Diagnostic and Statistical Manual of Mental Disorders (4th
      edition) somatoform diagnoses. Osteoarthritis and joint pain increase in
      prevalence from premenopausal- to menopausal-aged women with hormonal change
      implicated in their etiology. The current research on the relationships among
      menopause, depression, nociceptive mechanisms, perception and pain in the
      distressed midlife patient is discussed. The amelioration and management of pain
      symptoms in the menopausal and postmenopausal woman, with or without comorbid
      depression, have been elusive and difficult problems for clinicians. Familiarity
      with the differential diagnosis, pathophysiology and evidence-based treatment for
      such patients is crucial to their proper care.

PMID- 18039064
TI  - Role of psychiatric comorbidity on cognitive function during and after the
      menopausal transition.
AB  - While cognitive complaints are common during the menopausal transition,
      measurable cognitive decline occurs infrequently, often due to underlying
      psychiatric or neurological disease. To clarify the nature, etiology and evidence
      for cognitive and memory complaints during midlife, at the time of the menopausal
      transition, we have critically reviewed the evidence for impairments in memory
      and cognition associated with common comorbid psychiatric conditions, focusing on
      mood and anxiety disorders, attention-deficit disorder, prolonged stress and
      decreased quantity or quality of sleep. Both the evidence for a primary effect of
      menopause on cognitive function and contrarily the effect of cognition on the
      menopausal transition are examined. Impairment in specific aspects of executive
      function is explored. Evaluation and treatment strategies for the symptomatic
      menopausal woman distressed by changes in her day-to-day cognitive function with
      or without psychiatric comorbidity are presented.

PMID- 18039065
TI  - Impact of clinician and patient attitudes on clinical decision making for the
      symptomatic menopausal woman with or without comorbidity.
AB  - Culture, individual health beliefs and distressing symptoms frequently determine
      women's perceptions of their menopausal transitions. Women's perceptions of
      mental health problems and the acceptability of different interventions greatly
      affect if and what a woman is willing to try as a treatment option and whether or
      not she will accept the possibility that her menopausal symptoms represent a
      comorbidity with a diagnosis, such as depression or anxiety. These perceptions
      have a significant impact on women's choices with regard to health practices, as
      well as on whether or not they will seek out medical care for their distressing
      symptom(s). Working with a woman's beliefs, sharing decision making, and
      empowering her through health education are all critical aspects of the treatment
      of the patient with comorbid perimenopausal symptoms, regardless of their
      etiology.

PMID- 18039066
TI  - Series overview and introduction.
AB  - Studies and treatments for the symptomatic menopausal woman have been reviewed
      elsewhere. The aim of this clinical review series is to examine the evidence for
      the diagnosis and treatment of the woman who presents with distressing symptoms
      that she attributes to menopause, whose actual etiology may be a psychiatric
      disorder, a pre- or co-existing problem such as sleep or cognitive problems, or a
      dynamic interaction among one of these and a symptomatic menopause. This series
      of articles will review new research on somatic symptoms of depression, the
      depression continuum and its impact on morbidity and functioning, treatment
      issues related to remission of depression, cognitive decline or impairment
      secondary to a mood disorder, sleep problems in women and their impact on well
      being and functioning, and attention and working memory problems in women. These
      will all be reviewed in the context of the vulnerable female patient and her
      experience of increased or new distressing symptoms during her menopausal
      transition. Recommendations for the diagnosis and management of women with
      psychiatric comorbidity and a symptomatic menopause are discussed.

PMID- 18039067
TI  - Nomenclature and endocrinology of menopause and perimenopause.
AB  - The early and late perimenopausal transition is characterized by changing cycle
      length as well as by menopausal symptoms in some women, including increasing hot
      flashes and night sweats. Breast tenderness decreases as women enter the late
      transition. This review, as part of the clinical reviews on the menopausal woman
      with comorbidity, covers the endocrine phenomena of perimenopause, terminology
      and the observed clinical characteristics of the transition. It should be noted
      that the definitions covering this period vary between publications. The average
      duration of perimenopause is approximately 5A years. The earliest detectable
      hormonal change is a fall in ovarian secretion of inhibinA B, with a subsequent
      rise in follicle-stimulating hormone and maintained or increased levels of
      estradiol. As women transit the perimenopause, cycle irregularity increases, with
      the more frequent occurrence of prolonged ovulatory and anovulatory cycles.
      Levels of follicle-stimulating hormone and estradiol fluctuate increasingly and
      luteal function declines. Vasomotor symptoms tend to be most frequent around the
      time of final menses. The perimenopause is thus a time of cycle and hormone
      variability and single hormone measurements provide little useful information,
      with the clinical history being the most appropriate method of assessing
      menopausal status. This information will be very helpful to the clinician
      treating the concerned and symptomatic patient. It will also aid clinicians to
      avoid unnecessary laboratory testing and help them educate their patients about
      their perimenopause.

PMID- 18039068
TI  - Women, anxiety and mood: a review of nomenclature, comorbidity and epidemiology.
AB  - Women experience a high prevalence of mood and anxiety disorders, and comorbidity
      of mood and anxiety disorders is highly prevalent. Both mood and anxiety
      disorders disturb sleep, attention and, thereby, cognitive function. They result
      in a variety of somatic complaints. The mood disorder continuum includes minor
      depression, dysthymia, major depression and bipolar disorder. Chronobiological
      disorders, such as seasonal affective disorder as well as premenstrual dysphoric
      disorder, occur in some women, with comorbid seasonal affective disorder and
      premenstrual dysphoric disorder in just under half of these individuals [1] .
      Early life experience, heritability, gender, other psychiatric illness, stress
      and trauma all interact dynamically in the development of mood and anxiety
      disorders. The epidemiology, nomenclature and clinical diagnostic issues of these
      illnesses in midlife woman are reviewed.

PMID- 18039070
TI  - The menopause transition: the next neuroendocrine frontier.

PMID- 18039069
TI  - Collaborative depression care, screening, diagnosis and specificity of depression
      treatments in the primary care setting.
AB  - The identification, referral and specific treatment of midlife patients in
      primary care who are distressed by mood, anxiety, sleep and stress-related
      symptoms, with or without clinically confirmed menopausal symptoms, are
      confounded by many structural issues in the delivery of women's healthcare.
      Diagnosis, care delivery, affordability of treatment, time commitment for
      treatment, treatment specificity for a particular patient's symptoms and patient
      receptiveness to diagnosis and treatment all play roles in the successful
      amelioration of symptoms in this patient population. The value of screening for
      depression in primary care, the limitations of commonly used screening
      instruments relative to culture and ethnicity, and which clinical care systems
      make best use of diagnostic screening programs will be discussed in the context
      of the midlife woman. The Sequenced Treatment Alternatives to Relieve Depression
      (STAR*D) program illustrates the relatively high rate of unremitted patients,
      regardless of clinical setting, who are receiving antidepressants. Nonmedication
      treatment approaches, referred to in the literature as 'nonsomatic treatments',
      for depression, anxiety and stress, include different forms of cognitive
      behavioral therapy, interpersonal therapy, structured daily activities,
      mindfulness therapies, relaxation treatment protocols and exercise. The
      specificity of these treatments, their mechanisms of action, the motivation and
      time commitment required of patients, and the availability of trained
      practitioners to deliver them are reviewed. Midlife women with menopausal
      symptoms and depression/anxiety comorbidity represent a challenging patient
      population for whom an individualized treatment plan is often necessary.
      Treatment for depression comorbid with distressing menopausal symptoms would be
      facilitated by the implementation of a collaborative care program for depression
      in the primary care setting.

PMID- 18039071
TI  - Neurobehavioral impact of menopause on mood.
AB  - The menopausal transition is a time of risk for mood change ranging from distress
      to minor depression to major depressive disorder in a vulnerable subpopulation of
      women in the menopausal transition. Somatic symptoms have been implicated as a
      risk factor for mood problems, although these mood problems have also been shown
      to occur independently of somatic symptoms. Mood problems have been found to
      increase in those with a history of mood continuum disorders, but can also occur
      de novo as a consequence of the transition. Stress has been implicated in the
      etiology and the exacerbation of these mood problems. Estrogen and add-back
      testosterone have both been shown to positively affect mood and well-being. In
      most cases, the period of vulnerability to mood problems subsides when the
      woman's hormonal levels stabilize and she enters full menopause.

PMID- 18039072
TI  - Role of stressful life events and menopausal stage in wellbeing and health.
AB  - Stress plays an essential role in the development, continuation and exacerbation
      of mood problems throughout a woman's life. It exacerbates somatic symptoms of
      menopause, increasing the risk of recurrence of mood disorders, as well as of a
      mood disorder de novo throughout the lifespan and specifically in the menopausal
      transition. Chronic stress affects the hypothalamic-pituitary axis, hypothalamic
      pituitary-ovarian axis, the proinflammatory cytokines and cardiovascular risk.
      The current evidence for the potential interactions between acute stress, chronic
      stress, childhood stress and victimization, and individual susceptibility to the
      development of depression and/or anxiety in response to stressful life events,
      are reviewed in the context of the increasing data on the association of these
      and a symptomatic menopausal transition. Strategies for the optimal approach for
      clinicians to evaluate and treat the symptomatic perimenopausal patient with
      stressful life events and comorbid mood disorders are presented.

PMID- 18039073
TI  - Pharmacokinetic/pharmacodynamic indices: are we ready to use them in daily
      practice?

PMID- 18039074
TI  - NIH doubles funding for San Francisco AIDS research centers.

PMID- 18039075
TI  - Canada and the USA: Escherichia coli O157:H7.

PMID- 18039076
TI  - Pafuramidine for Pneumocystis jiroveci pneumonia in HIV-infected individuals.
AB  - Pneumocystis jiroveci pneumonia remains one of the major worldwide contributors
      to the morbidity and mortality of those with HIV infection. The mainstay of
      therapy for treatment is trimethoprim-sulfamethoxazole (TMP-SMX); however TMP-SMX
      may be associated with significant side effects and intolerability. In addition,
      TMP-SMX has a moderate pill burden with three- to four-times daily dosing
      schedule. Patients unable to tolerate TMP-SMX are confronted with either
      parenteral therapy or other oral agents that may be less efficacious or are
      associated with potential serious adverse reactions. Pafuramidine (DB289) is an
      orally bioavailable prodrug of furamidine (DB75), an investigational diamidine
      that is less toxic than previous diamidines such as pentamidine. To date, human
      trials suggest that pafuramidine is well tolerated overall and has clinical
      activity against Pneumocystis pneumonia. In this article, we review the available
      data for the use of pafuramidine in Pneumocystis pneumonia.

PMID- 18039077
TI  - Standard dosing regimen of liposomal amphotericin B is as effective as a high
      loading dose for patients with invasive aspergillosis: AmBiLoad trial.
AB  - Invasive mold infections continue to account for significant morbidity and
      mortality in immunocompromised patients; outcomes are dependent on both
      underlying host factors and appropriate therapy. The antifungal armamentarium has
      gradually increased during the past, with liposomal amphotericin B (L-AMB) being
      an important representative. Still, the question of what dose to use - a maximum
      tolerated or a minimum effective - has yet to be answered. On this basis, a
      randomized trial comparing a high-loading dose regimen with a standard dosing of
      L-AMB (AmBiLoad trial) for primary therapy of mold infections was initiated. No
      significant differences in response between the treatment groups were detected,
      although recipients of the 10-mg/kg daily dose experienced higher rates of
      nephrotoxicity and hypokalemia. Uncontrolled malignancy and allogeneic stem cell
      transplantation were significantly associated with poor survival. This article
      analyzes the study, discusses the rationale and the results and concludes that
      this study supports the routine application of L-AMB.

PMID- 18039078
TI  - Community-acquired pneumonia: is it time to shorten the antibiotic treatment?

PMID- 18039079
TI  - Cephalosporins in overcoming beta-lactamase-producing bacteria and preservation
      of the interfering bacteria in the treatment of otitis, sinusitis and
      tonsillitis.
AB  - The treatment of upper respiratory tract infections (URTIs) is complicated by the
      resurgence of beta-lactamase-producing bacteria (BLPB) and the absence of
      interfering bacteria. BLPB can have a direct pathogenic impact in causing the
      infection as well as an indirect impact through their ability to produce the
      enzyme beta-lactamase. BLPB may not only survive penicillin therapy but can also
      protect other penicillin-susceptible bacteria from penicillin. In this review,
      the clinical in vitro and in vivo evidence supporting the role of these organisms
      in the increased failure rate of penicillin in eradication of otitis, sinusitis
      and pharyngo-tonsillitis is outlined and the implication of that increased rate
      on the management of infections is discussed. Bacteria with interference
      capability of potential respiratory pathogens can prevent colonization and
      subsequent invasion by these organisms. These include alpha-hemolytic
      streptococci, nonhemolytic streptococci and Prevotella and Peptostreptococcus
      spp. Treatment with antimicrobials can affect the balance between the interfering
      organisms and potential pathogens. The role of bacterial interference in URTIs
      and its effect on their treatment is discussed. The use of some of the
      cephalosporins that are able to overcome the effect of BLPB and preserve the
      beneficial interfering bacteria can overcome and modulate these phenomena and
      achieve better cure of URTIs.

PMID- 18039080
TI  - Alternative mechanisms of action of cationic antimicrobial peptides on bacteria.
AB  - Cationic antimicrobial peptides are a novel type of antibiotic offering much
      potential in the treatment of microbial-related diseases. They offer many
      advantages for commercial development, including a broad spectrum of action and
      modest size. However, despite the identification or synthetic production of
      thousands of such peptides, the mode of action remains elusive, except for a few
      examples. While the dogma for the mechanism of action of antimicrobial peptides
      against bacteria is believed to be through pore formation or membrane barrier
      disruption, some peptides clearly act differently and other intracellular target
      sites have been identified. This article presents an updated review of how
      cationic antimicrobial peptides are able to affect bacterial killing, with a
      focus on internal targets.

PMID- 18039081
TI  - Update on prevalence and treatment of methicillin-resistant Staphylococcus aureus
      infections.
AB  - The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is
      characterized by variations (sometimes extreme) by country and geographic region.
      The conventional association of MRSA with healthcare settings has been upset by
      the emergence of community-associated MRSA infections in many areas. With this
      surge in MRSA comes a renewed interest in alternative agents to vancomycin for
      treatment of MRSA infections, including older drugs, such as clindamycin,
      doxycycline and trimethoprim- sulfamethoxazole. Newer agents, such as linezolid
      and daptomycin, are aiming to improve on the poor cure rates found with
      vancomycin in serious MRSA infections, but definitive studies showing superiority
      of these drugs are not yet available. Finally, the drug-development pipeline
      contains a number of agents for the treatment of MRSA infections, including
      enhanced glycopeptides (dalbavancin, oritavancin and telavancin) and anti-MRSA
      cephalosporins (ceftobiprole). As MRSA becomes the 'new normal' in many areas,
      clinicians will have to sort out the proper role of a dozen or more anti-MRSA
      drugs.

PMID- 18039082
TI  - Treatment of neurobrucellosis: what is known and what remains to be answered.
AB  - Neurological involvement is one of the most perplexing and diverse presentation
      complications of brucellosis, a worldwide prevalent zoonosis. This review
      presents the current knowledge available from medical literature and discusses
      the shortcomings of the existing data. A proposed regimen should include
      doxycycline and rifampicin and, with the benefit of doubt, ceftriaxone, since its
      high concentration in the cerebrospinal fluid may offer significant efficacy
      against the pathogen. Corticosteroids have been used in specialized situations.
      The use of streptomycin is discouraged owing to its questionable ability to
      penetrate into the cerebrospinal fluid and its potential neurotoxicity that may
      perplex the clinical presentation. Treatment duration should be individualized in
      the absence of an adequate cut-off index.

PMID- 18039083
TI  - Treatment of anaerobic infection.
AB  - Anaerobic bacteria are the predominant flora in the normal human skin and mucous
      membranes and are, therefore, a common cause of endogenous infections. Since
      anaerobic infections are generally polymicrobial, where anaerobes are mixed with
      aerobic organisms, therapy should provide coverage of both types of pathogens.
      The isolation of anaerobes requires appropriate methods of collection,
      transportation and cultivation of specimens. The lack of use of any of these
      methods can lead to inadequate recovery of anaerobes and inappropriate therapy.
      Treatment of anaerobic infection is complicated by the slow growth of these
      organisms and the growing resistance of anaerobic bacteria to antimicrobials. The
      primary role of antimicrobials is to limit the local and systemic spread of
      infection. Surgical drainage is of primary importance. This includes debriding of
      necrotic tissue, draining the pus, improving circulation, alleviating obstruction
      and increasing tissue oxygenation. The most effective antimicrobials against
      anaerobic organisms are metronidazole, the carbapenems (imipenem, meropenem and
      ertapenem), chloramphenicol, the combinations of a penicillin and a beta
      lactamase inhibitor (ampicillin or ticarcillin plus clavulanate, amoxicillin plus
      sulbactam, and piperacillin plus tazobactam), tigecycline and clindamycin.

PMID- 18039084
TI  - Controlling pathogenic inflammation to fungi.
AB  - The balance between pro- and anti-inflammatory signaling is a prerequisite for
      successful host-fungal interactions. Although inflammation is an essential
      component of the protective response to fungi, its dysregulation may
      significantly worsen fungal diseases and limit protective, antifungal immune
      responses. The newly described Th17 developmental pathway may play an
      inflammatory role previously attributed to uncontrolled Th1 cell responses. The
      capacity of regulatory T cells to inhibit aspects of innate and adaptive
      antifungal immunity, including functional Th17 antagonism, is required for
      protective tolerance to fungi. Indoleamine 2,3-dioxygenase and tryptophan
      catabolites contribute to such a homeostatic condition by providing the host with
      immune defense mechanisms adequate for protection, without necessarily
      eliminating fungal pathogens - which would impair immune memory - or causing an
      unacceptable level of tissue damage. These new findings provide a molecular
      connection between the failure to resolve inflammation and lack of antifungal
      immune resistance, and point to strategies for immune therapy of fungal
      infections that attempt to limit inflammation in order to stimulate an effective
      immune response.

PMID- 18039085
TI  - Treatment of cryptococcosis in the setting of HIV coinfection.
AB  - The HIV pandemic has been associated with a rise in the prevalence of primary and
      recurrent cryptococcosis. Evidence-based treatment algorithms exist for the use
      of antifungal drugs and maintaining normal intracranial pressure in HIV-infected
      hosts with cryptococcal meningitis. Further investigation is needed for the
      treatment of cases with refractory infections and cryptococcosis-related immune
      reconstitution syndrome, along with the optimal use of adjuvant therapies.
      Primary and secondary prevention strategies remain at the crux of global control
      strategies for cryptococcal disease.

PMID- 18039086
TI  - Antimicrobial prevention and therapy for travelers' infection.
AB  - International journeys are increasing and more than 70 million people from
      industrialized countries cross the borders of tropical countries every year. More
      than 50% of them will suffer from some form of infectious illness, ranging from
      mild travelers' diarrhea to severe dengue fever to fatal malaria, with a wide
      spectrum of microbiological entities. Travel-related respiratory infections,
      including TB, and sexually transmitted infections are also increasingly reported.
      Awareness of travel-related risk is not always adequate among international
      travelers. Specific training on travel medicine-related issues, as well as better
      diagnostic facilities for imported diseases, is crucial for physicians and nurses
      in industrialized countries.

PMID- 18039087
TI  - Host-microbe interaction: mechanisms of defensin deficiency in Crohn's disease.
AB  - Defensins are endogenous antibiotics with microbicidal activity against Gram
      negative and -positive bacteria, fungi, enveloped viruses and protozoa. A
      disturbed antimicrobial defense, as provided by Paneth and other epithelial cell
      defensins, seems to be a critical factor in the pathogenesis of Crohn's disease,
      an inflammatory disease of the intestinal tract. Different direct and indirect
      mechanisms leading to a breakdown of antimicrobial barrier function include
      direct changes in defensin gene numbers (e.g., copy number polymorphism), genetic
      mutations in pattern-recognition receptors (e.g., nucleotide-binding
      oligomerization domain 2) and, as described recently, a differentiation problem
      of epithelial stem cells mediated by the wingless type (Wnt) pathway. Knowledge
      regarding the regulation and biology of defensins provides an attractive target
      to open up new therapeutic avenues.

PMID- 18039088
TI  - Acne vulgaris: lasers, light sources and photodynamic therapy--an update 2007.
AB  - Inflammatory acne vulgaris remains one of the most common dermatologic disorders
      seen in clinical practice. Medical therapy remains the gold standard for therapy
      but recent advances have shown that a variety of lasers and light sources may be
      useful in the treatment of inflammatory acne vulgaris. In addition, the use of
      20% 5-aminolevulinic acid has found a useful niche in the treatment of moderate
      to-severe inflammatory acne vulgaris.

PMID- 18039091
TI  - Adventures in hepatocarcinogenesis.
AB  - Neoplasia is a heritably altered, relatively autonomous growth of tissue.
      Hepatocarcinogenesis, the pathogenesis of neoplasia in liver, as modeled in the
      rat exhibits three distinct, quantifiable stages: initiation, promotion, and
      progression. Simple mutations and/or epigenetic alterations may result in the
      irreversible stage of initiation. The stage of promotion results from selective
      enhancement of cell replication and selective inhibition of cellular apoptosis of
      initiated cells dependent on the genetic and/or epigenetic alterations of the
      latter. The irreversible stage of progression results from initial karyotypic
      alterations that evolve into greater degrees of genomic instability. The initial
      genomic alteration in the transition from promotion to progression may involve
      primarily epigenetic mechanisms driven by epigenetic and genetic alterations
      fixed during the stage of promotion.

PMID- 18039092
TI  - Endocrine functions of adipose tissue.
AB  - Obesity is a risk factor for type 2 diabetes, dyslipidemia, and cardiovascular
      disease. Dissection of the molecular mechanisms underlying obesity and its
      relationship to insulin resistance and the metabolic syndrome are essential for
      developing new strategies for prevention and treatment of these disorders. Both
      excess adipose tissue and lack of adipose tissue cause insulin resistance and
      dyslipidemia, suggesting that normal fat is required for the maintenance of
      systemic glucose and lipid homeostasis. Recent advances in obesity research have
      led to the recognition that adipose tissue is an active endocrine organ that
      secretes multiple bioactive factors termed adipokines. Secretion of adipokines
      provides a link between adipose tissue lipid accumulation and the metabolic
      function of other tissues such as liver and muscle. Dysregulation of adipokines
      is emerging as an important mechanism by which adipose tissue contributes to
      systemic insulin resistance and metabolic disease.

PMID- 18039093
TI  - Endometrial carcinoma.
AB  - Endometrial carcinoma, a common malignancy of the female genital tract, is
      composed of a number of tumor types with different light-microscopic features,
      molecular genetic alterations, and prognoses. In addition, hormonal influences
      significantly impact growth regulatory pathways and interact with genetic
      alterations in the pathogenesis of at least some types of endometrial carcinoma.
      These factors have complicated the analyses of endometrial carcinoma, but over
      the past decades, awareness of the different types of endometrial carcinoma, in
      addition to careful clinicopathological studies, molecular analyses, and animal
      studies of the biological underpinnings of the different tumor types, has
      increased. We present the current understanding of endometrial carcinoma, from a
      molecular vantage point, highlighting what are presently thought to be the
      fundamental pathways involved in the development and progression of the major
      types of endometrial carcinoma.

PMID- 18039094
TI  - Muscle diseases: the muscular dystrophies.
AB  - Dystrophic muscle disease can occur at any age. Early- or childhood-onset
      muscular dystrophies may be associated with profound loss of muscle function,
      affecting ambulation, posture, and cardiac and respiratory function. Late-onset
      muscular dystrophies or myopathies may be mild and associated with slight
      weakness and an inability to increase muscle mass. The phenotype of muscular
      dystrophy is an endpoint that arises from a diverse set of genetic pathways.
      Genes associated with muscular dystrophies encode proteins of the plasma membrane
      and extracellular matrix, and the sarcomere and Z band, as well as nuclear
      membrane components. Because muscle has such distinctive structural and
      regenerative properties, many of the genes implicated in these disorders target
      pathways unique to muscle or more highly expressed in muscle. This chapter
      reviews the basic structural properties of muscle and genetic mechanisms that
      lead to myopathy and muscular dystrophies that affect all age groups.

PMID- 18039095
TI  - Pathobiology of neutrophil transepithelial migration: implications in mediating
      epithelial injury.
AB  - Neutrophil (also known as polymorphonuclear leukocyte, or PMN) transepithelial
      migration and accumulation at mucosal surfaces is a hallmark of many inflammatory
      conditions. This process correlates directly with clinical disease activity and
      epithelial injury. Currently, the mechanisms that define PMN epithelial
      interactions during an inflammatory response are not completely understood. This
      review provides an overview of the consequences of PMN infiltration into
      epithelial tissues and highlights molecular details of PMN epithelial
      interactions during transmigration. A better understanding of this process will
      likely provide new insights into developing organ-specific treatment strategies
      to reduce the deleterious consequences of epithelial inflammation.

PMID- 18039096
TI  - Von Hippel-Lindau disease.
AB  - von Hippel-Lindau disease, which is characterized by an increased risk of
      hemangioblastomas, clear cell renal carcinomas, and pheochromocytomas, is caused
      by inactivating mutations of the VHL tumor suppressor gene. The VHL gene product,
      pVHL, has multiple functions, but the best documented, and the one most clearly
      linked to tumor development, relates to its role as the substrate recognition
      module of a ubiquitin ligase complex that targets hypoxia-inducible factor (HIF)
      for destruction. pVHL function is often compromised in sporadic kidney cancers,
      and inhibitors of the HIF-responsive growth factor (vascular endothelial growth
      factor) are active against this disease. pVHL, by inhibiting atypical protein
      kinase C and hence JunB, also affects neuronal survival, as do the products of
      the other genes linked to familial pheochromocytoma or paraganglioma (NF1, RET,
      SDHB, SDHC, and SDHD). It is hypothesized that tumor-associated alleles of these
      genes allow primitive sympathoadrenal precursors to escape developmental culling,
      and that such cells are at increased risk of forming tumors.

PMID- 18039097
TI  - Cancer stem cells: at the headwaters of tumor development.
AB  - According to the cancer stem cell hypothesis, only a subpopulation of cells
      within a cancer has the capacity to sustain tumor growth. This subpopulation of
      cells is made up of cancer stem cells, which are defined simply as the population
      of cells within a tumor that can self-renew, differentiate, and regenerate a
      phenocopy of the cancer when injected in vivo. Cancer stem cells have now been
      prospectively isolated from human cancers of the blood, breast, and brain, and
      putative cancer stem cells have been identified from human skin, bone, and
      prostate tumors and from multiple established mammalian cancer cell lines.
      Furthermore, researchers are actively seeking cancer stem cells in every human
      cancer type. We present the current scientific evidence supporting the cancer
      stem cell hypothesis and discuss the experimental and therapeutic implications of
      the discovery of human cancer stem cells.

PMID- 18039098
TI  - Neurofibromatosis.
AB  - As familial cancer syndromes, the neurofibromatoses exhibit complex phenotypes,
      comprising a range of tumor and nontumor manifestations. Although the three
      recognized forms of neurofibromatosis (NF1, NF2, and schwannomatosis) all feature
      the development of nervous system tumors, their underlying genetic bases are
      clearly distinct. The most prominent common feature of all three is the
      appearance of Schwann cell-initiated tumorigenesis of the peripheral nervous
      system. Recent progress in delineating the molecular function of the NF1- and NF2
      encoded proteins, together with the development and use of manipulable mouse
      models, has led to important advances in understanding the pathogenesis of many
      features of neurofibromatosis. An important outcome of the study of
      neurofibromatosis-associated tumorigenesis has been insight into the more general
      molecular and cellular bases of nervous system tumors.

PMID- 18039099
TI  - Malaria: mechanisms of erythrocytic infection and pathological correlates of
      severe disease.
AB  - Malaria is an ancient disease that continues to cause enormous human morbidity
      and mortality. The life cycle of the causative parasite involves multiple tissues
      in two distinct host organisms, mosquitoes and humans. However, all the clinical
      symptoms of malaria are a consequence of infection of human erythrocytes. An
      understanding of the basic mechanisms that govern parasite invasion, remodeling,
      growth, and reinvasion of erythrocytes and the complex events leading to tissue
      pathology may yield new diagnostics and treatments for malaria. This approach is
      revealing a more complete picture of the most serious syndrome associated with
      this infection-cerebral malaria. We focus on the most recent understanding of the
      molecular basis of infection, summarize our finding from an ongoing pediatric
      cerebral malaria autopsy study in Malawi, and integrate these insights to
      malarial pathology.

PMID- 18039100
TI  - VEGF-A and the induction of pathological angiogenesis.
AB  - Tumors, wounds, and chronic inflammatory disorders generate a new vascular supply
      by a process known as pathological angiogenesis. Whereas formation of the normal
      blood vasculature requires the interaction of many different agonists and
      inhibitors, including vascular endothelial growth factor-A (VEGF-A) and other
      members of the vascular permeability factor/VEGF family, pathological
      angiogenesis is a cruder, simpler process that can be replicated by a single VEGF
      A isoform, VEGF-A(164/5). VEGF-A(164/5) induces the formation of several
      distinctly different types of new blood vessels that differ from normal blood
      vessels with respect to organization, structure, and function. Elucidating the
      properties of these new vessels has led to a better understanding of angiogenesis
      and will hopefully lead to new approaches to antiangiogenic therapy.

PMID- 18039101
TI  - In vivo pathology: seeing with molecular specificity and cellular resolution in
      the living body.
AB  - The emerging tools of in vivo molecular imaging are enabling dynamic cellular and
      molecular analyses of disease mechanisms in living animal models and humans.
      These advances have the potential to dramatically change a number of fields of
      study, including pathology, and to contribute to the development of regenerative
      medicine and stem cell therapies. The new tools of molecular imaging, which have
      already had a tremendous impact on preclinical studies, hold great promise for
      bringing important and novel information to the clinician and the patient. These
      approaches are likely to enable early diagnosis, rapid typing of molecular
      markers, immediate assessment of therapeutic outcome, and ready measures of the
      extent of tissue regeneration after damage. However, the full impact of these new
      techniques will be determined by our ability to translate them to the clinic and
      to develop a general strategy that integrates them with other advances in
      molecular diagnostics and molecular medicine.

PMID- 18039102
TI  - Cell-based therapy for myocardial ischemia and infarction: pathophysiological
      mechanisms.
AB  - Cell-based cardiac repair has emerged as an attractive approach to preventing or
      reversing heart failure resulting from myocyte dysfunction-e.g., due to
      infarction-and to enhancing the development of collaterals in patients with
      symptoms of myocardial ischemia. These two problems involve both overlapping and
      differing mechanisms, and these differences must be considered in cell-based
      therapies. In terms of myocardial dysfunction due to infarction, only committed
      cardiomyocytes have been shown to form new myocardium that is electrically
      coupled with the host heart. Despite this, multiple cell populations appear to
      improve function of the infarcted heart, including many that are clearly
      nonmyogenic. In terms of myocardial ischemia, although cell-based strategies
      improve ischemia in animal models, clinical trials to date have not shown
      robustly beneficial results. We review the evidence for potential mechanisms
      underlying the benefits of cell transplantation in the heart and discuss the
      clinical contexts in which they may be relevant.

PMID- 18039103
TI  - Cystic disease of the kidney.
AB  - This review focuses on the mechanisms that underlie the development of human
      renal cystic diseases. A pathological, clinical, and pathophysiological overview
      is given. Initial analysis of the cell biology of inappropriate
      hyperproliferation accompanied by fluid secretion of cyst-lining epithelia has
      been followed by the elucidation of fundamental defects in epithelial polarity,
      cell-matrix and cell-cell interactions, and apoptosis, all of which are
      discussed. Identification of the genes and proteins responsible for several renal
      cystic diseases has led to a more complete understanding of defects in renal
      developmental programming, differentiation, and morphogenesis, all of which
      underlie cystic diseases of the kidney.

PMID- 18039104
TI  - Pathobiology of pulmonary hypertension.
AB  - A variety of conditions can lead to the development of pulmonary arterial
      hypertension (PAH). Current treatments can improve symptoms and reduce the
      severity of the hemodynamic abnormality, but most patients remain quite limited,
      and deterioration in their condition necessitates a lung transplant. This review
      discusses current experimental and clinical studies that investigate the
      pathobiology of PAH. An emerging theme is the consideration of ways in which one
      might reverse the advanced occlusive structural changes in the pulmonary
      circulation causing PAH. The current debate concerning the role of regeneration
      through stem cells is presented. This review also highlights investigations in a
      number of laboratories relating the pathobiology of PAH to mutations causing loss
      of function of bone morphogenetic protein receptor II in patients with familial
      PAH, as well as sporadic cases.

PMID- 18039105
TI  - Body traffic: ecology, genetics, and immunity in inflammatory bowel disease.
AB  - The abundant bacteria and other microbial residents of the human intestine play
      important roles in nutrient absorption, energy metabolism, and defense against
      microbial pathogens. The mutually beneficial relationship of host and commensal
      microbiota represents an ancient and major coevolution in composition and mutual
      regulation of the human mucosa and the resident microbial community. Inflammatory
      bowel disease (IBD) is a set of chronic, relapsing inflammatory intestinal
      diseases in which rules of normal host-microbial interaction have been violated.
      This review considers the components of this host-microbial mutualism and the
      ways in which it is undermined by pathogenic microbial traits and by host immune
      and epithelial functions that confer to them susceptibility in patients with IBD.
      Recent advances in understanding the genetics of IBD and the immunology of host
      microbial interaction are opening new strategies for treatments that target host
      susceptibility, candidate microbial pathogens, and intestinal ecology.

PMID- 18039106
TI  - A pathologist's odyssey.

PMID- 18039107
TI  - Immunobiology and pathogenesis of viral hepatitis.
AB  - Among the many viruses that are known to infect the human liver, hepatitis B
      virus (HBV) and hepatitis C virus (HCV) are unique because of their prodigious
      capacity to cause persistent infection, cirrhosis, and liver cancer. HBV and HCV
      are noncytopathic viruses and, thus, immunologically mediated events play an
      important role in the pathogenesis and outcome of these infections. The adaptive
      immune response mediates virtually all of the liver disease associated with viral
      hepatitis. However, it is becoming increasingly clear that antigen-nonspecific
      inflammatory cells exacerbate cytotoxic T lymphocyte (CTL)-induced
      immunopathology and that platelets enhance the accumulation of CTLs in the liver.
      Chronic hepatitis is characterized by an inefficient T cell response unable to
      completely clear HBV or HCV from the liver, which consequently sustains
      continuous cycles of low-level cell destruction. Over long periods of time,
      recurrent immune-mediated liver damage contributes to the development of
      cirrhosis and hepatocellular carcinoma.

PMID- 18039108
TI  - The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases.
AB  - Helicobacter pylori is the main cause of peptic ulceration, distal gastric
      adenocarcinoma, and gastric lymphoma. Only 15% of those colonized develop
      disease, and pathogenesis depends upon strain virulence, host genetic
      susceptibility, and environmental cofactors. Virulence factors include the cag
      pathogenicity island, which induces proinflammatory, pro-proliferative epithelial
      cell signaling; the cytotoxin VacA, which causes epithelial damage; and an
      adhesin, BabA. Host genetic polymorphisms that lead to high-level pro
      inflammatory cytokine release in response to infection increase cancer risk.
      Pathogenesis is dependent upon inflammation, a Th-1 acquired immune response and
      hormonal changes including hypergastrinaemia. Antral-predominant inflammation
      leads to increased acid production from the uninflamed corpus and predisposes to
      duodenal ulceration; corpus-predominant gastritis leads to hypochlorhydria and
      predisposes to gastric ulceration and adenocarcinoma. Falling prevalence of H.
      pylori in developed countries has led to a falling incidence of associated
      diseases. However, whether there are disadvantages of an H. pylori-free stomach,
      for example increased risk of esosphageal adenocarcinoma, remains unclear.

PMID- 18039109
TI  - Molecular pathology of malignant gliomas.
AB  - Malignant gliomas, the most common type of primary brain tumor, are a spectrum of
      tumors of varying differentiation and malignancy grades. These tumors may arise
      from neural stem cells and appear to contain tumor stem cells. Early genetic
      events differ between astrocytic and oligodendroglial tumors, but all tumors have
      an initially invasive phenotype, which complicates therapy. Progression
      associated genetic alterations are common to different tumor types, targeting
      growth-promoting and cell cycle control pathways and resulting in focal hypoxia,
      necrosis, and angiogenesis. Knowledge of malignant glioma genetics has already
      impacted clinical management of these tumors, and researchers hope that further
      knowledge of the molecular pathology of malignant gliomas will result in novel
      therapies.

PMID- 18039110
TI  - Tumor stroma and regulation of cancer development.
AB  - Abstract In the past 25 years, a majority of cancer studies have focused on
      examining functional consequences of activating and/or inactivating mutations in
      critical genes implicated in cell cycle control. These studies have taught us a
      great deal about the functions of oncogenes and tumor suppressor genes and the
      signaling pathways regulating cell proliferation and/or cell death. However, such
      studies have largely ignored the fact that cancers are heterogeneous cellular
      entities whose growth is dependent upon reciprocal interactions between
      genetically altered "initiated" cells and the dynamic microenvironment in which
      they live. This review highlights the aspects of cancer development that, like
      organogenesis during embryonic development and tissue repair in adult mammals,
      are regulated by interactions between epithelial cells, activated stromal cells,
      and soluble and insoluble components of the extracellular matrix.

PMID- 18039111
TI  - Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic
      implications.
AB  - Abstract Neurodegenerative diseases as diverse as Alzheimer's, Parkinson's, and
      Creutzfeldt-Jakob disease share a common pathogenetic mechanism involving
      aggregation and deposition of misfolded proteins, which leads to progressive
      central nervous system disease. Although the type of aggregated protein and the
      regional and cellular distribution of deposition vary from disease to disease,
      these disorders may all be linked by similar pathways of protein aggregation with
      fibril formation and amyloid deposition. This perspective on pathogenesis
      suggests that a wide variety of neurodegenerative diseases can be grouped
      mechanistically as brain amyloidoses, an outlook that yields novel insights into
      potential therapeutic approaches that may be applicable across the broad spectrum
      of neurodegenerative disease.

PMID- 18039112
TI  - The endothelium as a target for infections.
AB  - The endothelial cells lining vascular and lymphatic vessels are targets of
      several infectious agents, including viruses and bacteria, that lead to dramatic
      changes in their functions. Understanding the pathophysiological mechanisms that
      cause the clinical manifestations of those infections has been advanced through
      the use of animal models and in vitro systems; however, there are also abundant
      studies that explore the consequences of endothelial infection in vitro without
      supporting evidence that endothelial cells are actual in vivo targets of
      infection in human diseases. This article defines criteria for considering an
      infection as truly endothelium-targeted and reviews the literature that offers
      insights into the pathogenesis of human endothelial-target infections.

PMID- 18039113
TI  - Genetic regulation of cardiogenesis and congenital heart disease.
AB  - Developmental heart disorders are the most common of all human birth defects and
      occur in nearly one percent of the population. Survivors of congenital heart
      malformations are an increasing population, and it is becoming clear that genetic
      mutations that cause developmental anomalies may result in cardiac dysfunction
      later in life. This review highlights the progress in understanding the
      underlying molecular basis for cardiac formation and how disruption of the
      intricate steps of cardiogenesis can lead to congenital heart defects. The
      lessons learned from examining the early steps of heart formation are essential
      for informing the prevention of malformations and their long-term consequences,
      as well as for approaches to guide stem cells into cardiac lineages.

PMID- 18039114
TI  - Regulation of lung inflammation in the model of IgG immune-complex injury.
AB  - Modern techniques of cell and molecular biology have rapidly uncovered the
      mechanisms underlying inflammatory injury of the lung. This expanding knowledge
      (which includes an understanding of complement, cell surface receptors, cytokines
      and chemokines, transcription factors, oxidants, proteinases, and endogenous
      inhibitors, as well as the role of leukocyte adhesion-promoting molecules) has
      provided new insights into the inflammatory system in general, as well as in the
      context of lung injury. In this review, we summarize recent progress in
      understanding the regulation of lung inflammation by using immunoglobulin G (IgG)
      immune complex-induced lung injury as a model. These studies have provided
      information on the role of various inflammatory mediators and their sequence of
      engagement. Insights into potential interventional approaches for the suppression
      of inflammatory processes in humans have emerged from those studies.

PMID- 18039115
TI  - Integrative biology of prostate cancer progression.
AB  - Prostate cancer displays considerable clinical, morphological, and biological
      heterogeneity. Classical genetic techniques have provided only limited
      information about the pathogenesis of prostate cancer progression. Nevertheless,
      several candidate genes and pathways have been implicated in prostate cancer
      development. High-throughput techniques have exponentially expanded the number of
      candidate genes, including some whose role in prostate cancer pathogenesis has
      been studied. However, the techniques used to study the prostate cancer genome,
      transcriptome, and proteome generate massive amounts of data that have yet to be
      integrated and explored. To move beyond candidate gene identification and develop
      a comprehensive understanding of cancer pathogenesis, integrative approaches need
      to analyze this data on a global level. This review addresses candidate genes
      involved in prostate cancer pathogenesis in a biological and clinical context and
      demonstrates how integrated analysis of high-throughput data augments our
      understanding of prostate cancer.

PMID- 18039116
TI  - KSHV infection and the pathogenesis of Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) has long been suspected of having an infectious etiology on
      the basis of its unusual epidemiology, histopathology, and natural history.
      Nearly a decade ago, a novel herpesviral genome was discovered in KS biopsies,
      and since that time strong epidemiologic evidence has accumulated correlating
      infection with this KS-associated herpesvirus (KSHV, also known as human
      herpesvirus 8) with the development of the disease. Here we review the evidence
      linking KSHV infection to KS risk and discuss current notions of how KSHV gene
      expression promotes the development of this remarkable neoplasm. These studies
      show that both latent and lytic viral replicative cycles contribute significantly
      but differently-to KS development. The studies also highlight mechanistic
      differences between oncogenesis caused by KSHV and that caused by its distant
      relative Epstein-Barr virus.

PMID- 18039117
TI  - Inflammation and atherosclerosis.
AB  - Atherosclerosis, the cause of myocardial infarction, stroke, and ischemic
      gangrene, is an inflammatory disease. The atherosclerotic process is initiated
      when cholesterol-containing low-density lipoproteins accumulate in the intima and
      activate the endothelium. Leukocyte adhesion molecules and chemokines promote
      recruitment of monocytes and T cells. Monocytes differentiate into macrophages
      and upregulate pattern recognition receptors, including scavenger receptors and
      toll-like receptors. Scavenger receptors mediate lipoprotein internalization,
      which leads to foam-cell formation. Toll-like receptors transmit activating
      signals that lead to the release of cytokines, proteases, and vasoactive
      molecules. T cells in lesions recognize local antigens and mount T helper-1
      responses with secretion of pro-inflammatory cytokines that contribute to local
      inflammation and growth of the plaque. Intensified inflammatory activation may
      lead to local proteolysis, plaque rupture, and thrombus formation, which causes
      ischemia and infarction. Inflammatory markers are already used to monitor the
      disease process and anti-inflammatory therapy may be useful to control disease
      activity.

PMID- 18039118
TI  - Lung cancer preneoplasia.
AB  - From histological and biological perspectives, lung cancer is a complex neoplasm.
      Although the sequential preneoplastic changes have been defined for centrally
      arising squamous carcinomas of the lung, they have been poorly documented for the
      other major forms of lung cancers, including small cell lung carcinoma and
      adenocarcinomas. There are three main morphologic forms of preneoplastic lesions
      recognized in the lung: squamous dysplasias, atypical adenomatous hyperplasia,
      and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. However, these
      lesions account for the development of only a subset of lung cancers. Several
      studies have provided information regarding the molecular characterization of
      lung preneoplastic changes, especially for squamous cell carcinoma. These
      molecular changes have been detected in the histologically normal and abnormal
      respiratory epithelium of smokers. Two different molecular pathways have been
      detected in lung adenocarcinoma pathogenesis: smoking-associated activation of
      RAS signaling, and nonsmoking-associated activation of EGFR signaling; the latter
      is detected in histologically normal respiratory epithelium.

PMID- 18039119
TI  - Pathogenesis of nonimmune glomerulopathies.
AB  - Nonimmune glomerulopathies are an area of significant research. This review
      discusses the development of focal segmental glomerulosclerosis, with particular
      attention to the role of the podocyte in the initiation of glomerulosclerosis and
      the contribution to glomerulosclerosis from capillary hypertension and soluble
      factors such as transforming growth factor beta, platelet-derived growth factor,
      vascular endothelial growth factor, and angiotensin. The effects of these factors
      on endothelial and mesangial cells are also discussed. In addition, we review our
      current understanding of the slit diaphragm (a specialized cell junction found in
      the kidney), slit diaphragm-associated proteins (including nephrin, podocin,
      alpha-actinin-4, CD2-associated protein, and transient receptor potential channel
      6), and the role of these proteins in glomerular disease. We also discuss the
      most recent research on the pathogenesis of collapsing glomerulosclerosis, human
      immunodeficiency virus associated nephropathy, Denys-Drash, diabetic nephropathy,
      Alport syndrome, and other diseases related to the interaction between the
      podocyte and the glomerular basement membrane.

PMID- 18039120
TI  - Spectrum of Epstein-Barr virus-associated diseases.
AB  - The association between Epstein-Barr virus (EBV) and a large number of benign and
      malignant diseases is unique among DNA viruses. Within infected tissues, proteins
      that are expressed during the normal lytic and latent viral life cycle lead to
      cellular alterations that contribute to these EBV-associated diseases. Although
      the early events of EBV infection are poorly understood, increasing knowledge of
      the viral processes that govern viral latency has shed light upon the potential
      mechanisms by which EBV infection can lead to cellular transformation. Our
      current understanding of the role of EBV in the development of Burkitt lymphoma,
      Hodgkin lymphoma, nasopharyngeal carcinoma, and other EBV-associated diseases is
      discussed.

PMID- 18039121
TI  - Calcium in cell injury and death.
AB  - Loss of Ca(2+) homeostasis, often in the form of cytoplasmic increases, leads to
      cell injury. Depending upon cell type and the intensity of Ca(2+) toxicity, the
      ensuing pathology can be reversible or irreversible. Although multiple
      destructive processes are activated by Ca(2+), lethal outcomes are determined
      largely by Ca(2+)-induced mitochondrial permeability transition. This form of
      damage is primarily dependent upon mitochondrial Ca(2+) accumulation, which is
      regulated by the mitochondrial membrane potential. Retention of the mitochondrial
      membrane potential during Ca(2+) increases favors mitochondrial Ca(2+) uptake and
      overload, resulting in mitochondrial permeability transition and cell death. In
      contrast, dissipation of mitochondrial membrane potential reduces mitochondrial
      Ca(2+) uptake, retards mitochondrial permeability transition, and delays death,
      even in cells with large Ca(2+) increases. The rates of mitochondrial membrane
      potential dissipation and mitochondrial Ca(2+) uptake may determine cellular
      sensitivity to Ca(2+) toxicity under pathological conditions, including ischemic
      injury.

PMID- 18039122
TI  - Genetics of soft tissue tumors.
AB  - Sarcomas form a highly diverse group of rare tumors that are derived from
      connective tissue. More than 100 different malignant and benign soft tissue
      neoplasms can be recognized by histologic examination. Few diagnostic markers
      exist, and the cell of origin for many soft tissue tumors is unknown. The
      accurate diagnosis of many of these tumors therefore remains a challenge. The
      study of sarcomas has yielded many insights that can be applied to other
      neoplasms such as carcinoma. For example, the success of the treatment of
      gastrointestinal stromal tumor with Imatinib has led to an increased effort to
      find targeted therapies for other malignancies. Here we describe the known
      molecular changes in a number of sarcomas and focus on novel scientific
      approaches that can be expected to lead to improved diagnosis, prognostication,
      and therapy of sarcoma.

PMID- 18039123
TI  - Severe sepsis and septic shock: the role of gram-negative bacteremia.
AB  - Abstract Although Gram-negative bacteria have often been implicated in the
      pathogenesis of severe sepsis and septic shock, how they trigger these often
      lethal syndromes is uncertain. In particular, the role played by blood-borne
      bacteria is controversial. This review considers two alternatives. In the first,
      circulating Gram-negative bacteria induce toxic reactions directly within the
      vasculature; in the second, the major inflammatory stimulus occurs in local
      extravascular sites of infection and circulating bacteria contribute little to
      inducing toxic responses. Evidence for each alternative is found in the
      literature. Bacteremia and severe sepsis are not so closely linked that the most
      striking cases can be a model for the rest. Intravascular and extravascular
      triggers may warrant different approaches to prevention and therapy.

PMID- 18039124
TI  - Proteases in parasitic diseases.
AB  - Parasitic diseases represent major global health problems of immense proportion.
      Schistosomiasis, malaria, leishmaniasis, Chagas disease, and African sleeping
      sickness affect hundreds of millions of people worldwide, cause millions of
      deaths annually, and present an immense social and economic burden. Recent
      advances in genomic analysis of several of the major global parasites have
      revealed key factors involved in the pathogenesis of parasite diseases. Among the
      major virulence factors identified are parasite-derived proteases. This review
      focuses on the direct role of proteases in disease pathogenesis. Well
      characterized examples of the roles proteases play in pathogenesis include their
      involvement in invasion of the host by parasite migration through tissue
      barriers, degradation of hemoglobin and other blood proteins, immune evasion, and
      activation of inflammation.

PMID- 18039125
TI  - Modeling morphogenesis and oncogenesis in three-dimensional breast epithelial
      cultures.
AB  - Three-dimensional (3D) epithelial culture systems recreate the cardinal features
      of glandular epithelium in vivo and represent a valuable tool for modeling breast
      cancer initiation and progression in a structurally appropriate context. 3D
      models have emerged as a powerful method to interrogate the biological activities
      of cancer genes and oncogenic pathways, and recent studies have poignantly
      illustrated their utility in dissecting the emerging role of tensional force in
      regulating epithelial tissue homeostasis. We review how 3D models are being used
      to investigate fundamental cellular and biophysical mechanisms associated with
      breast cancer progression that have not been readily amenable to traditional
      genetic or biochemical analysis.

PMID- 18039127
TI  - The origins of medulloblastoma subtypes.
AB  - Childhood tumors containing cells that are morphologically and functionally
      similar to normal progenitor cells provide fertile ground for investigating the
      links between development and cancer. In this respect, integrated studies of
      normal cerebellar development and the medulloblastoma, a malignant embryonal
      tumor of the cerebellum, have proven especially fruitful. Emerging evidence
      indicates that the different precursor cell populations that form the cerebellum
      and the cell signaling pathways that regulate its development likely represent
      distinct compartments from which the various subtypes of medulloblastoma arise.
      Definitive characterization of each medulloblastoma subtype will undoubtedly
      improve treatment of this disease and provide important insights to the origins
      of cancer.

PMID- 18039128
TI  - The relevance of research on red cell membranes to the understanding of complex
      human disease: a personal perspective.
AB  - Molecular analysis in the service of research on human disease has finally come
      of age, as the chapters within this volume testify. Many technical advances,
      among them the development of recombinant DNA and its many applications, opened
      the way to study cells and processes that were unapproachable in the 1960s, when
      I first began my research career. The state of molecular biological studies at
      that time limited studies of human cell membrane proteins to experimental
      material most available and accessible, making the human erythrocyte membrane the
      favored target. I describe here how studies of red blood cell membrane proteins
      evolved and how results from those studies still inform present-day research.

PMID- 18039126
TI  - Notch signaling in leukemia.
AB  - Recent discoveries indicate that gain-of-function mutations in the Notch1
      receptor are very common in human T cell acute lymphoblastic leukemia/lymphoma.
      This review discusses what these mutations have taught us about normal and
      pathophysiologic Notch1 signaling, and how these insights may lead to new
      targeted therapies for patients with this aggressive form of cancer.

PMID- 18039129
TI  - Autophagy: basic principles and relevance to disease.
AB  - Autophagy is a process by which cytoplasmic components are sequestered in double
      membrane vesicles and degraded upon fusion with lysosomal compartments. In yeast,
      autophagy is activated in response to changes in the extracellular milieu.
      Depending upon the stimulus, autophagy can degrade cytoplasmic contents
      nonspecifically or can target the degradation of specific cellular components.
      Both of these have been adopted in higher eukaryotes and account for the
      expanding role of autophagy in various cellular processes, as well as contribute
      to the variation in cellular outcomes after induction of autophagy. In some
      cases, autophagy appears to be an adaptive response, whereas under other
      circumstances it is involved in cell death. In mammals, autophagy has been
      implicated in either the pathogenesis or response to a wide variety of diseases,
      including neurodegenerative disease, chronic bacterial and viral infections,
      atherosclerosis, and cancer. As the basic molecular pathways that regulate
      autophagy are elucidated, the relationship of autophagy to the pathogenesis of
      various disease states emerges.

PMID- 18039130
TI  - The aging brain.
AB  - Aging is accompanied by cognitive decline in a major segment of the population
      and is the primary risk factor for Alzheimer's disease and other prevalent
      neurodegenerative disorders. Despite this central role in disease pathogenesis
      and morbidity, the aging of the brain has not been well understood at a molecular
      level. This review seeks to integrate what is known about age-related cognitive
      and neuroanatomical changes with recent advances in understanding basic molecular
      mechanisms that underlie aging. An important issue is how normal brain aging
      transitions to pathological aging, giving rise to neurodegenerative disorders.
      Toxic protein aggregates have been identified as potential contributory factors,
      including amyloid beta-protein in Alzheimer's disease, tau in frontotemporal
      dementia, and alpha-synuclein in Parkinson's disease. However, current models of
      pathogenesis do not explain the origin of the common sporadic forms of these
      diseases or address the critical nexus between aging and disease. This review
      discusses potential approaches to unifying the systems biology of the aging brain
      with the pathogenesis of neurodegeneration.

PMID- 18039131
TI  - Molecular biology and pathogenesis of viral myocarditis.
AB  - Myocarditis is a cardiac disease associated with inflammation and injury of the
      myocardium. Several viruses have been associated with myocarditis in humans.
      However, coxsackievirus B3 is still considered the dominant etiological agent.
      The observed pathology in viral myocarditis is a result of cooperation or
      teamwork between viral processes and host immune responses at various stages of
      disease. Both innate and adaptive immune responses are crucial determinants of
      the severity of myocardial damage, and contribute to the development of chronic
      myocarditis and dilated cardiomyopathy following acute viral myocarditis.
      Advances in genomics and proteomics, and in the use of informatics and
      biostatistics, are allowing unbiased initial evaluations that can be the basis
      for testable hypotheses about virus pathogenesis and new therapies.

PMID- 18039132
TI  - The role of hypoxia in vascular injury and repair.
AB  - Although the terms ischemia and hypoxia are often used interchangeably, they
      represent distinct processes that result in different modulatory effects at the
      cellular level. Hypoxia is a reduction in oxygen delivery below tissue demand,
      whereas ischemia is a lack of perfusion, characterized not only by hypoxia but
      also by insufficient nutrient supply. Hypoxia can be either acute or chronic, and
      both are centrally regulated by hypoxia-inducible factor, a transcription factor
      that governs the expression of key response genes such as vascular endothelial
      growth factor and erythropoietin. Whereas severe chronic hypoxia can cause cell
      death, less-severe hypoxia can protect against subsequent damage, a phenomenon
      known as hypoxic conditioning. Several important processes are characterized by
      hypoxia, including ischemia-reperfusion, tumor growth and progression,
      inflammation, myocardial ischemia, and a number of ocular pathologies.

PMID- 18039134
TI  - Airway smooth muscle in asthma.
AB  - Airway smooth muscle plays a multifaceted role in the pathogenesis of asthma. We
      review the current understanding of the contribution of airway myocytes to airway
      inflammation, airway wall remodeling, and airflow obstruction in this prevalent
      disease syndrome. Together, these roles make airway smooth muscle an attractive
      target for asthma therapy.

PMID- 18039135
TI  - The osteoclast: friend or foe?
AB  - Bone is a dynamic organ constantly remodeled to support calcium homeostasis and
      structural needs. The osteoclast is the cell responsible for removing both the
      organic and inorganic components of bone. It is derived from hematopoietic
      progenitors in the macrophage lineage and differentiates in response to the tumor
      necrosis factor family cytokine receptor activator of NF kappa B ligand. alpha v
      beta 3 integrin mediates cell adhesion necessary for polarization and formation
      of an isolated, acidified resorptive microenvironment. Defects in osteoclast
      function, whether genetic or iatrogenic, may increase bone mass but lead to poor
      bone quality and a high fracture risk. Pathological stimulation of osteoclast
      formation and resorption occurs in postmenopausal osteoporosis, inflammatory
      arthritis, and metastasis of tumors to bone. In these diseases, osteoclast
      activity causes bone loss that leads to pain, deformity, and fracture. Thus,
      osteoclasts are critical for normal bone function, but their activity must be
      controlled.

PMID- 18039137
TI  - Gene expression profiling of breast cancer.
AB  - DNA microarray platforms for gene expression profiling were invented relatively
      recently, and breast cancer has been among the earliest and most intensely
      studied diseases using this technology. The molecular signatures so identified
      help reveal the biologic spectrum of breast cancers, provide diagnostic tools as
      well as prognostic and predictive gene signatures, and may identify new
      therapeutic targets. Data are best presented in an open access format to
      facilitate external validation, the most crucial step in identifying robust,
      reproducible gene signatures suitable for clinical translation. Clinically
      practical applications derived from full expression profile studies already in
      use include reduced versions of microarrays representing key discriminatory genes
      and therapeutic targets, quantitative polymerase chain reaction assays, or
      immunohistochemical surrogate panels (suitable for application to standard
      pathology blocks). Prospective trials are now underway to determine the value of
      such tools for clinical decision making in breast cancer; these efforts may serve
      as a model for using such approaches in other tumor types.

PMID- 18039136
TI  - Pancreatic cancer.
AB  - The past two decades have witnessed an explosion in our understanding of
      pancreatic cancer, and it is now clear that pancreatic cancer is a disease of
      inherited (germ-line) and somatic gene mutations. The genes mutated in pancreatic
      cancer include KRAS2, p16/CDKN2A, TP53, and SMAD4/DPC4, and these are accompanied
      by a substantial compendium of genomic and transcriptomic alterations that
      facilitate cell cycle deregulation, cell survival, invasion, and metastases.
      Pancreatic cancers do not arise de novo, and three distinct precursor lesions
      have been identified. Experimental models of pancreatic cancer have been
      developed in genetically engineered mice, which recapitulate the multistep
      progression of the cognate human disease. Although the putative cell of origin
      for pancreatic cancer remains elusive, minor populations of cells with stem-like
      properties have been identified that appear responsible for tumor initiation,
      metastases, and resistance of pancreatic cancer to conventional therapies.

PMID- 18039138
TI  - The pathology of influenza virus infections.
AB  - Influenza viruses are significant human respiratory pathogens that cause both
      seasonal, endemic infections and periodic, unpredictable pandemics. The worst
      pandemic on record, in 1918, killed approximately 50 million people worldwide.
      Human infections caused by H5N1 highly pathogenic avian influenza viruses have
      raised concern about the emergence of another pandemic. The histopathology of
      fatal influenza virus pneumonias as documented over the past 120 years is
      reviewed here. Strikingly, the spectrum of pathologic changes described in the
      1918 influenza pandemic is not significantly different from the histopathology
      observed in other less lethal pandemics or even in deaths occurring during
      seasonal influenza outbreaks.

PMID- 18039140
TI  - Molecular pathobiology of gastrointestinal stromal sarcomas.
AB  - Gastrointestinal stromal tumors (GISTs) form an interesting group of sarcomas
      whose unique pathobiology provides a model of how molecularly targeted
      therapeutics can have a major impact on patient welfare. Approximately 85% of
      GISTs are driven by oncogenic mutations in either of two receptor tyrosine
      kinases: KIT or platelet-derived growth factor receptor alpha. We review the
      pivotal relationship between specific mutations in these kinase genes, the origin
      and pathologic spectrum of GISTs, and the response of these tumors to treatment
      with kinase inhibitors such as imatinib and sunitinib. Mechanisms of resistance
      to kinase inhibitor therapy are discussed, and targets for the next generation of
      therapeutics are considered. The rapid evolution in our understanding of GISTs,
      which stems directly from the close alliance of basic and clinical researchers in
      the field, illustrates the growing role of the molecular classification of solid
      tumors in the development of modern oncological treatments.

PMID- 18039141
TI  - Molecular biology and pathology of lymphangiogenesis.
AB  - The lymphatic vasculature is essential for the maintenance of tissue fluid
      balance, immune surveillance, and adsorption fatty acids in the gut. The
      lymphatic vessels are also crucially involved in the pathogenesis of diseases
      such as tumor metastasis, lymphedema, and various inflammatory conditions.
      Attempts to control or treat these diseases have drawn a lot of interest to
      lymphatic vascular research during the past few years. Recently, several markers
      specific for lymphatic endothelium and models for lymphatic vascular research
      have been characterized, enabling great technical progress in lymphatic vascular
      biology, and many critical regulators of lymphatic vessel growth have been
      identified. Despite these significant achievements, our understanding of the
      lymphatic vessel development and pathogenesis is still rather limited. Several
      key questions remain to be resolved, including the relative contributions of
      different pathways targeting lymphatic vasculature, the molecular and cellular
      processes of lymphatic maturation, and the detailed mechanisms of tumor
      metastasis via the lymphatic system.

PMID- 18039139
TI  - Endoplasmic reticulum stress in disease pathogenesis.
AB  - The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane
      and secretory proteins, which, collectively, represent a large fraction of the
      total protein output of a mammalian cell. Therefore, the protein flux through the
      ER must be carefully monitored for abnormalities, including the buildup of
      misfolded proteins. Mammalian cells have evolved an intricate set of signaling
      pathways from the ER to the cytosol and nucleus, to allow the cell to respond to
      the presence of misfolded proteins within the ER. These pathways, known
      collectively as the unfolded protein response, are important for normal cellular
      homeostasis and organismal development and may also play key roles in the
      pathogenesis of many diseases. This review provides background information on the
      unfolded protein response and discusses a selection of diseases whose
      pathogenesis involves ER stress.

PMID- 18039142
TI  - Applications of proteomics to lab diagnosis.
AB  - Detailed and comprehensive characterization of proteins is a major goal of
      proteomics. This goal has become more realistic today with the latest high
      resolution mass spectrometers capable of faster sequencing in a high-throughput
      fashion and with the emergence of new techniques such as protein and peptide
      microarrays. A promising area for discovery is the application of these advanced
      mass spectrometric and other quantitative proteomic methodologies to laboratory
      diagnosis. This review focuses on the role of proteomics in the development of
      new laboratory diagnostics and the implications for routine diagnosis and
      monitoring of diseases.

PMID- 18039144
TI  - Kidney transplantation: mechanisms of rejection and acceptance.
AB  - We describe the molecular and cellular mechanisms believed to be responsible for
      the rejection of renal allografts, including acute T cell-mediated rejection,
      acute antibody-mediated (humoral) rejection, rejection mediated by the innate
      immune system, and chronic rejection. We present mechanisms of graft acceptance,
      including accommodation, regulation, and tolerance. Studies in animals have
      replicated many pathologic features of acute and chronic rejection. We illuminate
      the pathogenesis of human pathology by reflection from experimental models.

PMID- 18039145
TI  - Dependence of neovascularization mechanisms on the molecular microenvironment.
AB  - In vivo vascularization of implanted (bio)artificial constructs is essential for
      their proper function. Vascularization may rely on sprouting angiogenesis,
      vascular incorporation of bone marrow-derived endothelial cells (BMDECs), or
      both. Here we investigated the relative contribution of these 2 mechanisms to
      neovascularization in a mouse model of a foreign body reaction (FBR) to
      subcutaneously implanted Dacron and in hind limb ischemia (HLI) in relation to
      the molecular microenvironment at these neovascularization sites.
      Neovascularization was studied in C57Bl/6 mice reconstituted with enhanced green
      fluorescent protein (EGFP) transgenic bone marrow. Sprouting angiogenesis,
      detected using nuclear incorporation of bromodeoxyuridine in endothelial cells
      was present in both models, whereas vascular incorporation of EGFP(+) BMDECs was
      restricted to HLI. In HLI, the presence of a pro-angiogenic molecular
      microenvironment comprising vascular endothelial growth factor, fibroblast growth
      factor 2, and granulocyte colony-stimulating factor corroborated the importance
      of these factors for vascular BMDEC incorporation, whereas this microenvironment
      was absent in FBR. Enhanced mobilization of BMDECs by granulocyte-macrophage
      colony-stimulating factor administration or by combining HLI and FBR with Dacron
      did not induce incorporation of BMDECs in FBR neovessels. We conclude that the
      efficacy of BMDEC-based therapy is not generally warranted, but it depends on the
      molecular microenvironment in the targeted tissue.

PMID- 18039147
TI  - Rorschach Comprehensive System data for a sample of 190 Japanese nonpatient
      children at five ages.
AB  - This study is a part of our series of studies of nonpatient, Japanese children.
      In total, 346 children were administered the Rorschach. Thirty-two children had
      fewer than 10 responses, 112 children had more than 10 but fewer than 14
      responses, and 12 children were maladjusted or mentally retarded, for a total of
      156. In this study, we analyzed the remaining 190 children not excluded by the
      above criteria in the following age groups: 5 years (n = 24), 8 years (n = 43), 9
      years (n = 42), 12 years (n = 42), and 14 years (n = 39). Japanese children
      showed few responses generally, with an average of 18 ~ 20 responses. In addition
      to having fewer responses, other features of Japanese children are high Lambda,
      low EA, very high X-%, and low X+%. The fact that the Rorschach test depends on
      verbal expression may be one factor in all these features, and we should consider
      this study in view of these Japanese cultural factors. Interrater reliability
      findings and Rorschach Comprehensive System (CS; Exner, 1995; Matsumoto, 2003;
      Matsumoto et al., 2002) data are presented.

PMID- 18039143
TI  - The inflammatory response to cell death.
AB  - When cells die in vivo, they trigger an inflammatory response. The ensuing
      hyperemia, leak of plasma proteins, and recruitment of leukocytes serve a number
      of useful functions in host defense and tissue repair. However, this response can
      also cause tissue damage and contribute to the pathogenesis of a number of
      diseases. Given the key role of inflammation in these processes, it is important
      to understand the underlying mechanisms that drive this response. Injured cells
      release danger signals that alert the host to cell death. Some of these molecules
      are recognized by cellular receptors that stimulate the generation of
      proinflammatory mediators. Other molecules released by dead cells stimulate the
      generation of mediators from extracellular sources. The resulting mediators then
      orchestrate the inflammatory response, eliciting its various vascular and
      cellular components. Dead cells also release danger signals that activate
      dendritic cells and promote the generation of immune responses to antigens. Here
      we review what is presently known about the sterile inflammatory response and its
      underlying mechanisms.

PMID- 18039148
TI  - Rorschach Comprehensive System data for a sample of 108 normative subjects from
      The Netherlands.
AB  - The current study is part of a two-wave normative data collection study with the
      Rorschach Comprehensive System (CS; Exner, 2003) in The Netherlands. The first
      data wave yielded 108 valid Rorschach protocols for which descriptive data on CS
      variables were calculated. Interrater reliability between two raters for 10
      response segments on a subset of 24 protocols was good to excellent. The findings
      show that mean values for a number of important CS variables, such as EA,
      Egocentricity index, and WDA% in the Dutch sample are highly similar to those
      found in a recent U.S. study by Shaffer and colleagues (2007/this issue). On the
      other hand, the Dutch sample contains a higher percentage of subjects with
      positive scores on the DEPI and CDI, compared with the Shaffer et al. data, but
      to an even greater extent in comparison with Exner's (2001) nonpatient data. We
      argue, on the basis of findings from psychiatric epidemiology, that the exclusion
      of subjects with a history of mental disorder or mental health treatment from
      Rorschach normative data bases yields a dataset that is nonrepresentative of the
      general population.

PMID- 18039149
TI  - Rorschach Comprehensive System data for a sample of 233 adult nonpatients from
      Peru.
AB  - This study is composed of 233 adult nonpatients, all from Peru.
      Inclusion/exclusion criteria are described. Interrater reliability statistics at
      the response level are presented along with scores for the Rorschach
      Comprehensive System (CS; Exner & Erdberg, 2005). Considering the results of this
      investigation, the researcher suggests a line of multicultural research. The
      differences between the United States and Peru strengthen the psychometric and
      qualitative value of this line of investigation.

PMID- 18039150
TI  - Rorschach Comprehensive System data for a sample of 309 adult nonpatients from
      Portugal.
AB  - Three hundred and nine nonpatient adults, evenly distributed according to sex,
      age, educational level, and residence, took part in the Rorschach test study
      carried out in Portugal. The sample was drawn from selected regions of the
      country and was balanced for population density in urban and rural areas. Test
      administration was controlled through the services of psychologists familiar with
      the Rorschach Comprehensive System (CS; Exner, 1993). Results indicate that, in
      Portugal (Pires, 2000), level of education is the variable that seems to have the
      largest effect on Rorschach responding.

PMID- 18039151
TI  - Rorschach Comprehensive System data for a sample of 90 adult nonpatients from
      Argentina.
AB  - This study is composed of 90 nonpatient adults, ages 16 to 65, all from Buenos
      Aires and its suburban area. All of the data were gathered by the author.
      Inclusion and exclusion criteria are described and interrater reliability
      statistics at the response level are presented along with findings for the
      Rorschach Comprehensive System (CS; Exner, 2003). Results show that several
      variables yield values that deviated from the nonpatient ranges proposed by
      Exner, and these findings suggest the need for further exploration.

PMID- 18039152
TI  - Rorschach Comprehensive System data for a sample of 357 Portuguese children at
      five ages.
AB  - Eighteen examiners, well trained in the Comprehensive System (CS; Exner, 2003),
      administered the Rorschach to 357 Portuguese children, in the first through fifth
      grades, attending schools located in Lisbon and the surrounding neighborhood.
      Coding was done by 5 of the examiners, each one having more than 5 years of
      experience with the CS. For this study, coding was reviewed by the authors. Five
      records were randomly selected from each age group to assess intercoder
      reliability. Janson and Olsson's (2004) iota was used to assess reliability of
      the main variable categories. Results are high, with iota ranging from 0.87 to
      0.98 across the coding categories. CS variables are presented and key data were
      chosen and reviewed. A discussion of some data and their comparison with
      corresponding American data are made, permitting some interesting developmental
      and cross-cultural questions to be addressed.

PMID- 18039153
TI  - Rorschach Comprehensive System data for a sample of 111 adult nonpatients from
      Romania.
AB  - In this study Rorschach data from a Romanian sample of 111 respondents was
      collected and analyzed in a first attempt to establish national norms. The
      protocols were collected in a 5-year period (2002-2006) by the author. Interrater
      reliability statistics are presented for a sample of 20 cases, along with scores
      for the Rorschach Comprehensive System (CS; Exner, 1993). These results can be
      used for cross-cultural comparisons of the CS.

PMID- 18039154
TI  - Rorschach Comprehensive System data for a sample of 517 adults from Spain
      (Barcelona).
AB  - This study is composed of 517 adult voluntary participants, from Barcelona and
      its surroundings, all of whom are from Spain, Barcelona, and Catalonia. The study
      builds on a previously published report for a smaller sample (N = 250; see
      Alvarez, Baeza, Campo, Garcia, Guardia, et al., 1993) and is the result of
      collaboration between students and professors at the Barcelona Rorschach School
      (Catalan Rorschach Society). Our aim is to offer local data that should help to
      understand possible differences with existing reference data for the Rorschach
      Comprehensive System (CS; Exner, 2005), which is the system that has been taught
      at this school since 1978. Inclusion and exclusion criteria are described and
      interrater reliability statistics at the response level are presented, along with
      scores for the CS, followed by a discussion and very brief comparison with other
      international reference samples.

PMID- 18039155
TI  - A new U.S. adult nonpatient sample.
AB  - A project to collect an American adult nonpatient sample for the Rorschach
      Comprehensive System (CS; Exner, 2001) took place between 1999 and 2005, and this
      article presents data for 450 participants in the project. Inclusion criteria,
      demographic information, and interrater agreement statistics are described.
      Findings for most of the CS variables are similar to earlier Rorschach Workshops
      samples, but some differences emerged and their implications for modifying
      interpretive guidelines are discussed.

PMID- 18039156
TI  - Rorschach Comprehensive System data for a sample of 283 adult nonpatients from
      the United States.
AB  - This article presents an update on adult nonpatients living in central California
      previously described by Shaffer, Erdberg, and Haroian (1999). In this study an
      additional 160 nonpatients were administered the Rorschach for a total sample
      size of 283. Graduate students enrolled in a 2-year Rorschach research seminar
      administered the Rorschach (Exner, 1995), WAIS-R (Weschler, 1981), and MMPI-2
      (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989), and were provided with
      extensive supervision and ongoing quality control. All protocols were recoded by
      the first two authors and a psychologist with extensive Rorschach experience.
      Exclusion criteria are described. Interrater reliability statistics at the
      response level are presented along with scores for Rorschach Comprehensive System
      (CS), WAIS-R, and MMPI-2 variables.

PMID- 18039157
TI  - Rorschach Comprehensive System data for a sample of 52 older adult nonpatients
      from the United States.
AB  - This study is composed of 52 older adults, ages 60 to 80, all from the United
      States. In addition to being administered the Rorschach (Rorschach, 1942), all
      participants also were administered the Wechsler Adult Intelligence Scale-Revised
      (WAIS-R; Weschler, 1981), the Minnesota Multiphasic Personality Inventory-2 (MMPI
      2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989), the Neuro Cognitive
      Status Examination (NCSE; Kiernan, Mueller, Langston, & Van Dyke, 1987), and the
      Trail Making Test Part B (Reitan, 1958; Reitan & Wolfson, 1993). Examiners
      included the principal author as well as three other trained examiners. Inclusion
      criteria are described. Interrater reliability statistics at the response level
      are presented along with scores for the Rorschach Comprehensive System (CS;
      Exner, 1995).

PMID- 18039158
TI  - Rorschach Comprehensive System data for 100 nonpatient children from the United
      States in two age groups.
AB  - Building on our previously published study (Hamel, Shaffer, & Erdberg, 2000),
      which provided data on 100 nonpatient children aged 6 to 12 from the United
      States, we here provide reference data for two more homogeneous age subgroups: 6
      to 9 (N = 50) and 10 to 12 (N = 50). Inclusion criteria are described, and
      expanded interrater reliability statistics at the response level are presented
      along with scores for the Rorschach Comprehensive System (CS; Exner, 2001) at
      each age grouping. In addition to the children being administered the Rorschach,
      their parents were given the Conners' Parent Rating Scale-93 (CPRS-93; Conners,
      1989), and these results are presented as well.

PMID- 18039159
TI  - Rorschach Comprehensive System data for a sample of 42 nonpatient Mexican
      American children from the United States.
AB  - This study is composed of 42 Mexican American children, ages 8 to 10 years, all
      from the United States. In addition to the children being administered the
      Rorschach, they also were administered the Children's Hispanic Background Scale
      (CHBS) and the Children's Personality Questionnaire (CPQ). The principal author
      was the sole examiner. Inclusion criteria are described. Interrater reliability
      statistics at the response level are presented along with scores for the
      Rorschach Comprehensive System (CS; Exner, 1995).

PMID- 18039160
TI  - Rorschach Comprehensive System data for a sample of 37 nonpatient/nondelinquent
      adolescents from the United States.
AB  - This study is composed of 37 American adolescents, ages 15 to 17 years of age,
      all from the United States. The principal author was the sole examiner. Inclusion
      criteria are described. Interrater reliability statistics at the response level
      are presented along with scores for the Rorschach Comprehensive System (CS;
      Exner, 2003). The results revealed differences from the published norms on
      variables that reflect poor form quality, fewer popular responses, more attention
      to detail, more poor human relationship responses, and a more simplistic,
      affective-free approach to the environment, among others.

PMID- 18039161
TI  - The impact of administration and inquiry on Rorschach Comprehensive System
      protocols in a national reference sample.
AB  - We investigated the impact of administration and inquiry skills on Rorschach
      Comprehensive System (CS; Exner, 1974, 1991, 1993) protocols collected for the
      Italian adult nonpatient reference sample. The same research team collected CS
      protocols on two occasions. The initial reference sample (N = 212; Lis, Rossi, &
      Priha, 1998) was collected under the supervision of experienced psychologists who
      carefully studied CS administration and scoring procedures (Exner, 1986, 1990,
      1993). The second sample (N = 101; Lis, Zennaro, Calvo, & Salcuni, 2001) was
      collected after the team obtained additional and sustained CS training from
      Rorschach workshops certified instructors. Both samples were scored, reliably but
      they showed large differences on many codes, with protocols from the second
      sample being richer and more complex than the first. The results indicate that
      administration skills can have a dramatic impact on CS protocols and may
      contribute to variations in samples collected by different investigators.
      Training standards should be devised to insure uniform administration procedures
      are followed when collecting CS protocols.

PMID- 18039162
TI  - Introduction to the JPA special supplement on International Reference Samples for
      the Rorschach Comprehensive System.
AB  - This Introduction provides an overview to the JPA Special Supplement on
      International Reference Samples for the Rorschach Comprehensive System (CS;
      Exner, 2001). It contains a history of this project and a table including all of
      the lead authors, their country and the type and size of their sample.
      Suggestions for conducting this type of research are offered, including
      information on normative vs. nonpatient samples, inclusion/exclusion criteria,
      the use of collateral instruments, and concerns relative to representativeness.
      Reliability and coding concerns are addressed, and information on the Popular
      response in Japan are reviewed. Finally, trends within and across the data are
      highlighted.

PMID- 18039163
TI  - Rorschach Comprehensive System data for a sample of 128 adult nonpatients from
      Australia.
AB  - This article examines data collected for the study by Greenway and Milne (2001),
      which investigated the association between the Capacity for Control and Stress
      Tolerance cluster of the Rorschach Comprehensive System (CS; Exner, 1995) and the
      ability of individuals to take control of their internal states -- emotional,
      cognitive and those related to their actions and reactions. The data consisted of
      the Rorschach protocols of 128 participants in an urban, community sample,
      collected by graduate students in the second year of a master's degree in
      counseling psychology. All of these students had been trained thoroughly in
      administering the Rorschach and had experience in practicing psychological
      assessment and counseling for between 8 and 11 months in professional settings.
      The exclusion criteria are described and the interrater reliability statistics
      for several CS variables as well as descriptive statistics are presented.

PMID- 18039164
TI  - Toward international normative reference data for the comprehensive system.
AB  - We build on the work of all the authors contributing to this Special Supplement
      by summarizing findings across their samples of data, and we also draw on samples
      published elsewhere. Using 21 samples of adult data from 17 countries we create a
      composite set of internationally-based reference means and standard deviations
      from which we compute T-scores for each sample. Figures illustrate how the scores
      in each sample are distributed and how the samples compare across variables in
      eight Rorschach Comprehensive System (CS; Exner, 2003) clusters. The adult
      samples from around the world are generally quite similar, and thus we encourage
      clinicians to integrate the composite international reference values into their
      clinical interpretation of protocols. However, the 31 child and adolescent
      samples from 5 countries produce unstable and often quite extreme values on many
      scores. Until the factors contributing to the variability among these samples are
      more fully understood, we discourage clinicians from using many CS scores to make
      nomothetic, score-based inferences about psychopathology in children and
      adolescents.

PMID- 18039166
TI  - Rorschach Comprehensive System data for a sample of 100 adult nonpatients from
      the Belgian French-speaking community.
AB  - This article presents normative data for the Rorschach Comprehensive System (CS)
      on 100 adult nonpatients from the Belgian French-speaking community. We compare
      our Belgian sample to a French one (Sultan et al., 2004), data of Exner's (Exner
      & Erdberg, 2005) and a Californian sample (Shaffer, Erdberg, & Haroian, 1999).
      Each sample's specific characteristics are explored, as well as findings provided
      by sample-specific comparisons. Exner's data, ultimate normative reference for
      the CS, differ significantly from the three other samples for many variables.
      Cultural factors, examiner's level of experience, as well as participants'
      selection and recruitment, presumably flow into calculated differences between
      the four samples. Our findings indicate the necessity for constituting normative
      data for different communities, as well as the indispensability of examiners'
      familiarity with the CS, in order to provide reliable clinical information.

PMID- 18039167
TI  - Rorschach Comprehensive System data for a sample of 409 adult nonpatients from
      Brazil.
AB  - This is a normative study with 409 adult nonpatients living in the state of Sao
      Paulo, Brazil. The Rorschach was administered by a team of nine psychologists;
      eight had had further training in the Rorschach method by the Brazilian Rorschach
      Society and one intensively was prepared by the project coordinator. Of the study
      participants, 200 lived in the state capital (Sao Paulo) and the other 209 were
      in other large and small cities in the state, including a coastal city and one in
      the mountains. Previous psychological or psychiatric treatments were criteria for
      exclusion. Each protocol was coded independently by two examiners, and then
      agreement of the two codings was checked. Differences between the two codings
      were discussed in a meeting of the whole team, which was supervised by the
      project coordinator to guarantee codification quality control. Upon completion of
      the codings, an analysis of examiner differences was undertaken, the results of
      which are in the text. Interrater reliability statistics among examiners were
      calculated, including percentage of agreement and kappa. Reliability statistics
      among examiners at the response level are presented as are Comprehensive System
      (CS; 1999, 2003) findings.

PMID- 18039168
TI  - Rorschach Comprehensive System data for a sample of 141 adult nonpatients from
      Denmark.
AB  - A sample (n = 141) of Danish nonpatients 25-50 years of age, never hospitalized
      with a psychiatric diagnosis and currently employed, was demographically
      representative of two geographical areas of Copenhagen with different social
      strain. The sample, as well as 45 persons not currently employed, was tested with
      the Rorschach (Exner, 1995), MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, &
      Kaemmer, 1989), Word Association Test (Ivanouw, 1999b), WAIS Comprehension
      subtest (Hess, 1974), and SCL-90-R (Olsen, Mortenson, & Bech, 2006). Half of the
      persons contacted volunteered for the study. There was no difference in rate of
      volunteering between a standard no-feedback condition and a feedback condition;
      the latter, however, tended to attract more psychologically resourceful persons.
      The employed persons tended to appear healthier than the not employed. Response
      style of the subjects, quality of the Rorschach protocols, reliability of
      scoring, and the effect of the data being grouped on geographical area and
      examiner were examined. Form level, color, texture, cooperative movement, and EA
      were lower than in the Comprehensive System (CS; n = 450) sample, but higher than
      in nine international nonpatient Rorschach studies. Unique for the Danish sample
      was a low number of animal movement answers. The Rorschach data showed women to
      be healthier than men. Differences in Rorschach variables based on educational
      level were small.

PMID- 18039169
TI  - Rorschach Comprehensive System data for a sample of 75 Danish 9-year-old
      children: a pilot study.
AB  - This article provides a normative study documenting how 75 Danish nonpatient 9
      year-old children respond to the Rorschach test. The children were selected
      randomly from nine different parts of Denmark and tested with the Rorschach by 10
      different psychologists. All examiners were familiar with the Comprehensive
      System (CS; Exner, 2003), and before the data collection they participated in a 3
      day workshop performed by the research group that focused on administration,
      inquiry, and scoring issues. Among the results are an average R of 23.6 and an
      average Lambda of 2.01 (median = 1.18). Slightly more than 60% of the sample had
      an Avoidant style (63%); 41% had a CDI of 4 or 5; and 33% were positive on the
      HVI. In terms of perception and thinking, average values were .44 for X+%, .27
      for X-%, and 9.4 for the WSum6.

PMID- 18039170
TI  - Rorschach Comprehensive System data for a sample of 343 adults from Finland.
AB  - This article combines Rorschach Comprehensive System (CS; Exner, 1990, 1993) data
      from four projects conducted in Finland between 1990 and 1995. The projects
      studied a stratified random sample of Finnish nonpatients, a cohort of twins, a
      group of elderly men, and a random sample collected to investigate sleep
      difficulties. The 343 records from these four studies provide a representative
      survey of Rorschach responding throughout the Finnish population.

PMID- 18039171
TI  - Rorschach Comprehensive System data for a sample of 98 adult nonpatients from
      Greece.
AB  - Ninety-eight adult nonpatients from Greece were administered the Rorschach
      according to the Rorschach Comprehensive Systems (CS; Exner, 2003) procedures.
      These participants were of Greek heritage, were older than 21 years of age, and
      resided in Greece. Participants were residents of an urban area, Athens, as well
      as residents of provincial areas including smaller cities and villages. The
      examiner was a native Greek and of Greek heritage and administered the protocols
      in Greek. Exclusion criteria are described. Interrater reliability statistics at
      the response level are presented along with scores for CS variables.

PMID- 18039172
TI  - Rorschach Comprehensive System data for a sample of 150 adult nonpatients from
      Israel.
AB  - This study is composed of 150 adult nonpatients, all from Israel, who were
      administered the Rorschach. Inclusion/exclusion criteria are described. Senior
      graduate students from the clinical psychology program at Bar-Ilan University
      administered the Rorschach and were provided with extensive supervision and
      ongoing quality control. Interrater reliability statistics at the response level
      are presented along with scores for the Rorschach Comprehensive System (CS;
      Exner, 2005).

PMID- 18039173
TI  - Rorschach Comprehensive System data for a sample of 506 adult nonpatients from
      Argentina.
AB  - This study is composed of 506 nonpatient adults, ages 18 to 65, all from
      Argentina. The data were gathered by five examiners, who tested most of the
      participants at their work site. Inclusion and exclusion criteria are described
      and interrater reliability statistics at the response level are presented along
      with findings for the Rorschach Comprehensive System (CS; Exner, 1994).

PMID- 18039174
TI  - Rorschach Comprehensive System data for a sample of 41 adult nonpatients from
      Israel.
AB  - This study presents data concerning Rorschach protocols of 41 Jewish Israeli
      students. The sample includes 20 males and 21 females, ranging in age from 19 to
      35, who were selected from a larger sample of 50 undergraduates by applying
      psychiatric exclusion criteria. The results concerning the main Rorschach
      Comprehensive System's (CS; Exner, 2003) measures of distress (D and Adj D
      scores, S-Constellation, and DEPI) revealed substantial elevation. These results
      are analyzed in relation to the constant threat of terror, which the participants
      are exposed to within the context of the ongoing political conflict in the Middle
      East. The analysis is supported by data concerning a new Rorschach index, the
      Reality-Fantasy scale (RFS; Tibon, Handelzalts, & Weinberger, 2005), which
      applies the CS to psychoanalytic conceptualization of transitional space.

PMID- 18039175
TI  - Rorschach Comprehensive System data for a sample of 249 adult nonpatients from
      Italy.
AB  - This project provides information on how Italian adult nonpatients perform on the
      Rorschach test administered and scored following Rorschach Comprehensive System
      (CS) guidelines (Exner, 1995). Lis, Zennaro, Calvo, and Salcuni (2001) reported
      previously initial data for 101 of the nonpatients who were administered this
      instrument between July 1998 and February 2001 by graduate and postgraduate
      students in a 2-year research course at the Psychotherapy School of the
      University of Padua. The current study extends that previous work and includes
      information on an additional 148 participants gathered between April 2001 and
      March 2004, for a total of 249 individuals. Exclusion criteria are described and
      interrater reliability statistics at the response level for scoring segments are
      reported using both percent of agreement and iota. Comprehensive System findings
      are presented.

PMID- 18039176
TI  - Rorschach Comprehensive System data for two samples of nonpatient children from
      Italy: 75 aged 5-7 years and 148 aged 8-11 years.
AB  - This project provides information on how nonpatient children perform on the
      Rorschach test, administered and scored following Exner's guidelines (1995). Lis,
      Parolin, Zennaro, and Mazzeschi (2001) previously reported initial data for 70
      nonpatient children living in Italy who were administered this instrument by
      graduate and postgraduate students in a 2-year research course at the
      Psychotherapy School of the University of Padua between July 1998 and February
      2001. The current study is an extension of that work and includes information on
      an additional 153 participants gathered between November 2002 and December 2006.
      The total number of participants includes 223 individuals, 75 5-7-year-old
      children in the first level of elementary school, and 148 8-11-year-old children
      in the second level of elementary school. Exclusion criteria are described, and
      interrater reliability statistics at the response level for scoring segments are
      reported using percent agreement and iota. Rorschach Comprehensive System (CS)
      findings are presented.

PMID- 18039177
TI  - Rorschach Comprehensive System data for a sample of 116 preadolescent and 117
      adolescent nonpatients from Italy.
AB  - This project provides information on how preadolescent and adolescent nonpatients
      perform on the Rorschach test, administered and scored following Exner's
      guidelines (2003). Lis, Salcuni, Parolin, and Superchi (2001) reported previously
      initial data for 51 adolescent nonpatients living in Italy who were administered
      this instrument by graduate and postgraduate students in a 2-year research course
      at the Psychotherapy School of the University of Padua, between July 1998 and
      February 2001. The current study is an extension of that work and includes
      information on additional adolescent nonpatients and preadolescent nonpatients,
      gathered between April 2001 and December 2006. The study thus includes
      information on 233 participants, 116 preadolescents (aged 12-14) and 117
      adolescents (aged 15-18). Individuals were excluded if they had a major medical
      illness in the past 6 months, any psychiatric hospitalization, psychological
      treatment within the past 2 years, any felony conviction, or psychological
      testing within the past year. Interrater reliability statistics at the response
      level for scoring segments are reported both with percentage of agreement and
      iota. Rorschach Comprehensive System (CS) findings are presented.

PMID- 18039178
TI  - Rorschach Comprehensive System data for a sample of 240 adult nonpatients from
      Japan.
AB  - This article presents Rorschach Comprehensive System (CS; Exner, 1995) results
      for 240 adult nonpatients living in the central area of Tokyo, Japan.
      Inclusion/exclusion criteria are described. Interrater reliability statistics at
      the response level are presented along with scores for CS variables.

PMID- 18039180
TI  - Molecular identification of three Arabidopsis thaliana mitochondrial
      dicarboxylate carrier isoforms: organ distribution, bacterial expression,
      reconstitution into liposomes and functional characterization.
AB  - Screening of the Arabidopsis thaliana genome revealed three potential homologues
      of mammalian and yeast mitochondrial DICs (dicarboxylate carriers) designated as
      DIC1, DIC2 and DIC3, each belonging to the mitochondrial carrier protein family.
      DIC1 and DIC2 are broadly expressed at comparable levels in all the tissues
      investigated. DIC1-DIC3 have been reported previously as uncoupling proteins, but
      direct transport assays with recombinant and reconstituted DIC proteins clearly
      demonstrate that their substrate specificity is unique to plants, showing the
      combined characteristics of the DIC and oxaloacetate carrier in yeast. Indeed,
      the Arabidopsis DICs transported a wide range of dicarboxylic acids including
      malate, oxaloacetate and succinate as well as phosphate, sulfate and thiosulfate
      at high rates, whereas 2-oxoglutarate was revealed to be a very poor substrate.
      The role of these plant mitochondrial DICs is discussed with respect to other
      known mitochondrial carrier family members including uncoupling proteins. It is
      proposed that plant DICs constitute the membrane component of several metabolic
      processes including the malate-oxaloacetate shuttle, the most important redox
      connection between the mitochondria and the cytosol.

PMID- 18039181
TI  - Oxidation of myosin by haem proteins generates myosin radicals and protein cross
      links.
AB  - Previous studies have reported that myosin can be modified by oxidative stress
      and particularly by activated haem proteins. These reactions have been implicated
      in changes in the properties of this protein in food samples (changes in meat
      tenderness and palatability), in human physiology (alteration of myocyte function
      and force generation) and in disease (e.g. cardiomyopathy, chronic heart
      failure). The oxidant species, mechanisms of reaction and consequences of these
      reactions are incompletely characterized. In the present study, the nature of the
      transient species generated on myosin as a result of the reaction with activated
      haem proteins (horseradish peroxidase/H2O2) and met-myoglobin/H2O2) has been
      investigated by EPR spectroscopy and amino-acid consumption, product formation
      has been characterized by HPLC, and changes in protein integrity have been
      determined by SDS/PAGE. Multiple radical species have been detected by EPR in
      both the presence and the absence of spin traps. Evidence has been obtained for
      the presence of thiyl, tyrosyl and other unidentified radical species on myosin
      as a result of damage-transfer from oxidized myoglobin or horseradish peroxidase.
      The generation of thiyl and tyrosyl radicals is consistent with the observed
      consumption of cysteine and tyrosine residues, the detection of di-tyrosine by
      HPLC and the detection of both reducible (disulfide bond) and non-reducible cross
      links between myosin molecules by SDS/PAGE. The time course of radical formation
      on myosin, product generation and cross-link induction are consistent with these
      processes being interlinked. These changes are consistent with the altered
      function and properties of myosin in muscle tissue exposed to oxidative stress
      arising from disease or from food processing.

PMID- 18039179
TI  - A role for PFK-2/FBPase-2, as distinct from fructose 2,6-bisphosphate, in
      regulation of insulin secretion in pancreatic beta-cells.
AB  - PFK-2/FBPase-2 (6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase) catalyses
      the formation and degradation of fructose 2,6-P(2) (fructose 2,6-bisphosphate)
      and is also a glucokinase-binding protein. The role of fructose 2,6-P(2) in
      regulating glucose metabolism and insulin secretion in pancreatic beta-cells is
      unresolved. We down-regulated the endogenous isoforms of PFK-2/FBPase-2 with
      siRNA (small interfering RNA) and expressed KA (kinase active) and KD (kinase
      deficient) variants to distinguish between the role of PFK-2/FBPase-2 protein and
      the role of its product, fructose 2,6-P(2), in regulating beta-cell function.
      Human islets expressed the PFKFB2 (the gene encoding isoform 2 of the
      PFK2/FBPase2 protein) and PFKFB3 (the gene encoding isoform 3 of the PFK2/FBPase2
      protein) isoforms and mouse islets expressed PFKFB2 at the mRNA level [RT-PCR
      (reverse transcription-PCR)]. Rat islets expressed PFKFB2 lacking the C-terminal
      phosphorylation sites. The glucose-responsive MIN6 and INS1E cell lines expressed
      PFKFB2 and PFKFB3. PFK-2 activity and the cell content of fructose 2,6-P(2) were
      increased by elevated glucose concentration and during pharmacological activation
      of AMPK (AMP-activated protein kinase), which also increased insulin secretion.
      Partial down-regulation of endogenous PFKFB2 and PFKFB3 in INS1E by siRNA
      decreased PFK-2/FBPase-2 protein, fructose 2,6-P(2) content, glucokinase activity
      and glucoseinduced insulin secretion. Selective down-regulation of glucose
      induced fructose 2,6-P(2) in the absence of down-regulation of PFK-2/FBPase-2
      protein, using a KD PFK-2/FBPase-2 variant, resulted in sustained glycolysis and
      elevated glucose-induced insulin secretion, indicating an over-riding role of PFK
      2/FBPase-2 protein, as distinct from its product fructose 2,6-P(2), in
      potentiating glucose-induced insulin secretion. Whereas down-regulation of PFK
      2/FBPase-2 decreased glucokinase activity, overexpression of PFK-2/FBPase-2 only
      affected glucokinase distribution. It is concluded that PFK-2/FBPase-2 protein
      rather than its product fructose 2,6-P(2) is the over-riding determinant of
      glucose-induced insulin secretion through regulation of glucokinase activity or
      subcellular targeting.

PMID- 18039182
TI  - Extracellular point mutations in FGFR2 result in elevated ERK1/2 activation and
      perturbation of neuronal differentiation.
AB  - Two independent gain-of-function point mutations (S252W and P253R) in the
      extracellular region of the FGFR2 (fibroblast growth factor receptor 2) increase
      the binding affinity for the growth factor. The effect of this enhanced growth
      factor binding by these mutants is expected to be an increase in activation of
      regular signalling pathways from FGFR2 as a result of more receptors being
      engaged by ligand at any given time. Using PC12 (pheochromocytoma) cells as a
      model cell system we investigated the effect of these mutations on protein
      phosphorylation including the receptor, the activation of downstream signalling
      pathways and cell differentiation. Our results show that the effects of both of
      these extracellular mutations have unexpected intracellular phenotypes and
      cellular responses. Receptor phosphorylation was altered in both the ligand
      stimulated and unstimulated states. The mutants also resulted in differential
      phosphorylation of a number of intracellular proteins. Both mutations resulted in
      enhanced ERK1/2 (extracellular-signalregulated kinase1/2) activation. Although
      ERK1/2 activation is believed to transduce signals resulting in cell
      differentiation, this response was abrogated in the cells expressing the mutant
      receptors. The results of the present study demonstrate that single extracellular
      point mutations in the FGFR2 have a profound effect on intracellular signalling
      and ultimately on cell fate.

PMID- 18039183
TI  - Novel recombinant thrombolytic and antithrombotic staphylokinase variants with an
      RGD motif at their N-termini.
AB  - To develop a more potent thrombolytic agent, four Sak (staphylokinase) variants
      were constructed, in which RGD (Arg-Gly-Asp) sequences are introduced into
      diferent sites of the N-terminus of Sak. These variants were successfully
      expressed in Escherichia coli DH5alpha as soluble cytoplasmic proteins in a 5
      litre fermentor and accounted for more than 40% of the total cellular protein.
      The expressed proteins were subsequently purified, employing a similar three-step
      chromatographic purification process. SDS/PAGE and HPLC-MS analyses indicated
      that the purified proteins were almost completely homogeneous, the purity of the
      variants exceeding 95%. Further investigations into the properties of the Sak
      variants showed that mutations at the N-terminus significantly affected N
      terminal methionine excision, and serine residues at the N-terminus of Sak
      appeared to play an important role in the process. Kinetic analysis of r-Sak
      (recombinant Sak) and its variants using plasminogen as substrate indicated that
      the mutations affected the proteolysis. In addition, a significant inhibitory
      effect of the Sak variants at 2.0 muM was observed on the ADP-induced aggregation
      of platelets compared with that of r-Sak, whether N-terminally cleaved or not
      (P<0.05). Furthermore, the inhibitory activity of Sak variants after N-terminal
      proteolysis was higher than that of native Sak variants.

PMID- 18039185
TI  - Central nervous system birth defects in surgically treated infants in Sarajevo
      region of Bosnia and Herzegovina.
AB  - Congenital anomalies of the central nervous system (CNS) are common. The
      prevalence of these anomalies shows considerable geographical variation and
      female predominance. The aim of this work was to obtain the frequency of
      different CNS congenital anomalies types and their sex distribution among cases
      hospitalized in a Department of Neurosurgery, University of Sarajevo Clinics
      Center, Bosnia and Herzegovina, during the period January 2001 to December 2004.
      Retrospective study was carried out on the basis of the clinical records.
      Standard methods of descriptive statistics were performed for the data analysis.
      A total of 103 cases were surgically treated in the period from 2001 through
      2004. Out of that number 56 (54.4%) were female patients, while 47 (46.6%) were
      male patients. Seven different CNS birth defect types were found in this
      investigation. These were: spina bifida (42 cases or 40.78%), congenital
      hydrocephalus (35 cases or 33.98%), arachnoid cyst (15 cases or 14.56%), Dandy
      Walker syndrome (5 cases or 4.85%), dermoid cyst (4 cases or 3.88%), one of
      Arnold-Chiari syndrome (0.98%) and one of encephalocele (0.98%). According to
      this investigation, CNS congenital birth defects were slightly higher in females
      (54.4%). The most frequent types were spina bifida (40.78%) both in females
      (22.33%) and in males (18.45%), hydrocephalus (33.98%) and arachnoid cyst
      (14.56%). The anomalies of the other organ systems, associated with CNS anomalies
      obtained in this investigation, were pes equinovarus, cheiloschisis, cardiomegaly
      and palatoschisis. They were found in six cases (5.82%), equal in both sexes.

PMID- 18039186
TI  - Research on spontaneously emerged chromosomal aberrations in the periphery blood
      lymphocytes in cattle ('Busa' breed).
AB  - Knowledge of spontaneous aberrations, namely, of their frequency in non
      irradiated cells is of paramount importance not only in cytogenetic research, but
      also in contemporary animal production. The paper deals with research on
      spontaneously emerged chromosomal aberrations in the peripheral blood lymphocytes
      in the cattle of 'Busa' breed. To obtain metaphase chromosomes the conventional
      method of lymphocyte cultivation was used, albeit slightly modified and adapted
      to the examined animals and the laboratory conditions. The research findings
      indicate that a certain percent of spontaneously emerged chromosomal aberrations
      of chromatid type (gap and break) have been found in the peripheral blood
      lymphocytes in the cattle of 'Busa' breed.

PMID- 18039187
TI  - N-terminal pro-brain natriuretic peptide (NT-proBNP) serum concentrations in
      apparently healthy Bosnian women.
AB  - Brain natriuretic peptide (BNP) is a cardiac hormone secreted predominantly from
      the ventricles. This hormone is produced as pre-prohormone BNP (pro BNP), than
      cleaved by corine to biologically active 32-aminoacid BNP and non-biologically
      active N-terminal-pro brain natriuretic peptide (NTproBNP). NTproBNP has been
      found to be a useful marker for the diagnosis of heart failure and left
      ventricular systolic dysfunction. Recent studies showed that concentration of BNP
      and NTproBNP predict cardiovascular disease in apparently healthy individuals but
      their full screening characteristics are not firmly established. As NTproBNP
      serum concentration is altered by numerous factors there are also interindividual
      variations in NTproBNP values. There are no previous results for Bosnian
      population so the aim of this study was to asses normal range of NTproBNP serum
      concentrations in apparently healthy women using electrochemiluminescence
      immunoassay (Elecsys, Roche Diagnostic). A group of 45, healthy females, aged
      39.19 (+/-6.62), were enrolled in this study. Mean serum concentration of
      NTproBNP was 60.32 (+/-36.25) pg/ml, with the range of 112,60 pg/ml (minimum
      maximum: 13.6-126.00 pg/ml). We conclude that NTproBNP serum concentration in
      apparently healthy Bosnian women was not different from the average values of
      NTproBNP obtained on Europen's population. Thus, we suggest that the NTproBNP
      serum upper cut off values measured by using electrochemiluminescence immunoassay
      "ECLIA" (Elecsys 2010, Roche Diagnostic) for Bosnian females, aged < or =50
      years, should be 155 pg/ml as reported by Roche Diagnostic.

PMID- 18039188
TI  - Chromosome aberrations as bioindicators of environmental genotoxicity.
AB  - Due to the exposure to various potentially genotoxic xenobiotics, derived from
      recent war activities such as NATO air strikes with antitank ammunition
      containing depleted uranium, we have evaluated chromosome aberrations in 84
      peripheral blood samples from three local populations. One population sample
      included 30 individuals who lived in the Sarajevo area during and after the war
      (exposed to potential genotoxins), second population was presented with 26
      employees of the tank repair facility in Hadzici (target of NATO air strikes),
      and 28 inhabitants of Posusje (not exposed to war-related activities) were
      treated as sample of control population. The mean of chromosome aberration
      frequencies for the population from Hadzici was significantly higher than the
      frequencies for the two other populations. Point bi-serial coefficient analysis
      did not reveal any relationship between the frequencies of chromosome aberrations
      and smoking habits or gender. Results suggest that depleted uranium could be a
      risk factor for human health.

PMID- 18039189
TI  - Antioxidant capacity in the lipophilic fraction of Alzheimer's brain tissues.
AB  - The aim of this study was to investigate the antioxidant capacity (AC) in the
      lipophilic fraction of postmortem motorcortex (MC), nucleus caudatus (NC) and
      gyrus temporalis (GT) from controls (C) and Alzheimer's disease (AD) patients.
      The initial samples consisted of 50 human brain tissues of AD and C. AC of the
      different region of human brain were measured by using the fluorescent method of
      the oxygen radical absorbance capacity (ORAC). Peroxyl and hydroxyl radical
      generators were used in the analysis. All ORAC analysis were carried out on the
      Perkin-Elmer spectrofluorometer LS 55 with fluorescent filters, Ex: 485 nm; Em:
      520 nm. Final results were calculated using the differences between area under
      the quenching curve of fluorescein (FL), blank and analyzed biological samples.
      AC against peroxyl radicals (ORAC-ROO degrees ) of lipophilic fraction in MC of
      AD was statistically significantly lower in comparison with MC of C (p < 0.008).
      No changes in the AC against hydroxyl radicals (ORAC- degrees OH) of lipophilic
      fraction of AD were found in comparison with C. Reduction of total protein in GT
      of AD (p < 0.03) was found. The results showed that in the MC of AD brain the
      balance between production of free radicals and the neutralization by a complex
      antioxidant system is disturbed. The manual fluorescent method for AC
      measurements proved to be sufficiently appropriate and sensitive for the AC
      measurements of lipophilic fraction of postmortem brain tissues from different
      patologic conditions.

PMID- 18039190
TI  - Serum C-reactive protein concentration and measures of adiposity in patients with
      type 2 diabetes mellitus.
AB  - We investigated serum concentration of C-reactive protein (CRP) and measures of
      adiposity in 30 patients with type 2 diabetes mellitus (15 male, 15 female) and
      30 age and sex-matched apparently healthy subjects. CRP concentration was
      determined by laser nephelometry (BN II Analyzer) and CardioPhase high
      sensitivity CRP (DADE BEHRING) was used as reagent which consists of polystyrene
      particles coated with mouse monoclonal antibodies to CRP. Results have shown that
      serum CRP concentration in patients with type 2 diabetes mellitus was
      statistically significantly higher compared to control group of healthy subjects
      (p<0,05). Body mass index (BMI) correlated significantly with serum concentration
      of CRP in patients with type 2 diabetes mellitus (r=0.614; p<0.001).
      Statistically significant positive correlation was also found between waist to
      hip ratio and serum CRP concentration in patients with type 2 diabetes mellitus
      (r=0.426; p<0.05). Elevated serum CRP concentration in patients with type 2
      diabetes mellitus is probably caused by the presence of chronic low-grade
      inflammation in these patients. It is possible that determined increase of CRP
      concentration reflects activation of innate immune system components in patients
      with type 2 diabetes mellitus. Implications of established association between
      measures of adiposity and serum CRP level in type 2 diabetes mellitus remain
      unclear.

PMID- 18039191
TI  - Influence of tablet splitting on content uniformity of
      lisinopril/hydrochlorthiazide tablets.
AB  - Dose-related adverse effects of medications are a major problem in modern medical
      practice. The "correct" dose, based on drug company guidelines in package
      inserts, may not be correct for many patients. Tablet splitting or dividing has
      been an accepted practice for many years as a means of obtaining the prescribed
      dose of medication. As model tablets for this investigation, two batches of
      lisinopril- hydrochlorothiazide scored tablets labeled to contain 20/12.5 mg were
      used. The aim of this study was to establish possible influence of tablet
      splitting on content uniformity of lisinopril/hydrochlorthiazide tablets.
      Determination of the content uniformity of lisinopril and hydrochlorthiazide in
      our batches, was carried out by HPLC method. The results of content uniformity
      studies for halves of tablets containing combination of lisinopril
      hydrochlorthiazide (supposed to contain 50% of stated 20/12.5 mg in the whole
      tablet) were: 49.60 +/-3.29% and 49.29+/-0.60 % (lisinopril); 50.33+/-3.50% and
      50.69+/-1.95% (hydrochlorthiazide) for batch I and II, respectively. We can
      conclude that the results obtained in this study support an option of tablet
      splitting, which is very important for obtaining the required dosage when a
      dosage form of the required strength is unavailable, and for better
      individualization of the therapy.

PMID- 18039192
TI  - Effect of biphasic insulin aspart 30 combined with metformin on glycaemic control
      in obese people with type 2 diabetes.
AB  - Combination therapy consisting of biphasic insulin aspart 30 bid with metformin
      provide better glycaemic control in obese patients with diabetes mellitus type 2.
      In our study, patients who were treated with 2550 mg of metformin, administered
      in three daily doses had poor glycaemic control. Three months after switching
      from metformin therapy to treatment with biphasic insulin aspart 30 + metformin
      twice a day, glycaemic control improved with significant reduction in hemoglobin
      HbA1c, fasting blood glucose and postprandial blood glucose levels. Biphasic
      insulin aspart 30 in combination with metformin administered twice a day may be
      recommended as a starting insulin treatment in obese diabetic persons whose
      glycaemic control remained poor while on oral metformin therapy alone.

PMID- 18039193
TI  - Echocardiographic monitoring of patients with heart failure.
AB  - Twenty seven patients diagnosed as having systolic heart failure with Ejection
      Fraction (EF) of less than 40% by echocardiography were monitored over a period
      of 3 years. The monitored parameters included clinical symptoms, diastolic
      dysfunction, therapies and survival during three years of treatment. The results
      indicate a beneficial effect of treatment with high doses of ACE-inhibitors,
      spironolactone and beta-blockers in improving clinical symptoms and diastolic
      function. The survival rate was similar to that in the developed European
      countries.

PMID- 18039194
TI  - The effects of inducible nitric oxide synthase inhibitor L-N6-(1-iminoethyl)
      lysine in gentamicin-induced acute tubular necrosis in rats.
AB  - The aim of this study was to investigate the role of inducible nitric oxide
      synthase (iNOS) in gentamicin-induced acute tubular necrosis in rats using the
      iNOS inhibitor L-N6-(1-iminoethyl) lysine (L-NIL). Wistar rats, both sexes
      (n=18), were equally divided into three groups. Gentamicin group received
      intraperitoneally (i.p.) gentamicin in 0.9 % NaCl at a dose of 80 mg/kg/day for
      five consecutive days. L-NIL+gentamicin group received L-NIL at a dose of 3 mg/kg
      i.p. 36, 24 and 12 h before first dose of gentamicin. Control group received 0.9
      % NaCl i.p. for five consecutive days at the equal volume as gentamicin group.
      Griess reaction was used for determination plasma level of NO. Semiquantitative
      histological analysis was used for the evaluation of kidney damage level. The
      plasma NO level and the level of kidney damage were statistically higher in
      gentamicin group in comparison to the control group (p=0.046). Application of L
      NIL prior to gentamicin led to certain decrease in the plasma level of NO as well
      as in the level of kidney damage. Application of L-NIL, prior to gentamicin
      administration, did not provide complete protective effects of L-NIL on the
      kidney, which was demonstrated on kidney sections. The lack of anticipated
      protective effect of L-NIL on kidney tissue might be explained with the fact that
      we have used L-NIL prior but not during/after gentamicin administration. It would
      be necessary to examine the effects of L-NIL administration not only before, but
      as well during and possibly after the administration of gentamicin.

PMID- 18039196
TI  - No changes in serum concentrations of interleukin 10 (IL-10) and interferon gamma
      (IF-gamma) before and after treatment of the thyroid eye disease (TED).
AB  - TED is a severe eye disease leading in rare cases to decrease of sight, optic
      nerve compression and blindness. Recently, significant progresses in
      understanding the disease have been done. Nevertheless, the treatment of the
      disease, especially in its severe form remains challenging. Glucocorticoids (GC)
      have been the basis of the treatment for a long time. Orbital irradiation (OI)
      and optical decompression (OD) are also used in managing the severe forms of TED.
      Somatostatin, intravenous immunoglobulin have been also used, with conflicting
      results. Regarding the potential for the treatment of TED with cytokine
      antagonists, controlled clinical studies are not available. Since cytokines play
      an important role in the pathogenesis of the TED, they seemed to be logical
      choice for modern TED treatment. It has been shown that both Th1 (interleukin-2,
      tumor necrosis factor gamma, interleukin gamma) and Th2 (interleukin -4, -5, -10)
      profile T cells are activated in the TED. We therefore measured interleukin
      gamma, IF-gamma and interleukin -10 (IL-10)(Th1 and Th2 pattern) to assess its
      relationship to the course of the disease. This paper shows that both Th1 (IL-2)
      and Th2 (IF-gamma) pathways represented by those two cytokines are not involved
      (IL-10 before 2.29+/-5.23 and after treatment 3.77+/-8.44; IF gamma before 0.50+/
      0.24 and after treatment 0.35+/-0.19). No relationship to the response to
      treatment was found. GC resulted in positive response in 8/22 patients, OI (12
      patients) given after CS therapy, resulted in a response in all patients.
      Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD
      in two patients, who both recovered visual acuity and proptosis fell under 25 mm
      Hertel.

PMID- 18039195
TI  - The role of inhalatory corticosteroids and long acting beta(2) agonists in the
      treatment of patients admitted to hospital due to acute exacerbations of chronic
      obstructive pulmonary disease (AECOPD).
AB  - There is the question about the role of fixed combination of inhalatory
      corticosteroids and long acting beta(2) agonists in the treatment of patients
      admitted in hospital due to AECOPD. The objective of this study is to determine
      the frequency of etiologic factors of AECOPD, to research the length of recovery
      time and the time free from exacerbation due to AECOPD at the patients treated
      with fixed combination inhalers containing F/S versus patients who were not
      treated with this combination. This is retrospective-prospective, randomized,
      clinical study with a sample size of 70 patients who admitted to hospital due to
      AECOPD type I or II. Patients are randomized in two groups. Prospective group
      from 36 patients have been treated with oral or parenteral corticosteroids 7-14
      days, other medications and fixed combination inhalers containing a F/S. Second,
      retrospective group from 34 patients have been treated with oral or parenteral
      corticosteroids 7-14 days (in time when we didn't have fixed combination inhalers
      containing a F/S) and other medications. In both groups (prospective and
      retrospective) the most frequent etiological factors of AECOPD was bacterial
      infection, after that viral infection, other factors as well as congestive heart
      failure. Average recovery time for symptoms of AECOPD was statistically
      significant shorter in group patients treated with fixed combination inhalers
      containing F/S (prospective group) than in group treated without this fixed
      combination. There are also significant differences in average number of days
      need for recovery in subgroups of patients by etiological factors of AECOPD,
      except in cases of AECOPD onset because of congestive heart failure. Average free
      time from exacerbation at the patients treated with fixed combination inhalers
      was statistically significant longer than in group of patients who were not
      treated with this combination. In this study has demonstrated the presence of
      pathogenic bacteria in 53% our patients hospitalized due to AECOPD. There were
      26% patients whose exacerbation is signed as viral origin. 11% cases had
      congestive heart failure. Average recovery time for non-viral AECOPD was 14.8
      days and for exacerbations of viral origin 27.4 days. Average free time from
      exacerbation at the patients treated with fixed combination inhalers containing a
      F/S was statistically significant longer than in group of patients who were not
      treated with this combination. There were no statistically significant
      differences in average number of exacerbation during the year, between observed
      groups.

PMID- 18039197
TI  - Treatment of the spasticity in children with cerebral palsy.
AB  - Botulinum toxin is a natural purified protein and one of the strongest biological
      poisons--neurotoxin. It is produced by the bacterium Clostridium botulinum. Its
      medical usage started in USA in 1981 and in Europe in 1992. There are seven
      different immune types of the toxin: A, B, C1, D, E, F and G. Toxin types A and B
      are used to decrease muscular spasticity. Botulinum toxin prevents the formation
      of acetylcholine from cholinergic nerve tissues in muscles, which in the end
      irreversibly destroys neuromuscular synapses. It is called temporary local
      chemodenervation. It does not affect the synthesis of acetylcholine. As it
      affects neuromuscular bond it also affects one of the symptoms of cerebral palsy-
      spasticity. Decreasing the spasticity of children with cerebral palsy leads to
      the improvement of conscious movements, muscles are less toned, passive mobility
      is improved, orthosis tolerance is also improved, and the child is enabled to
      perform easier and better motor functions such as crawling, standing and walking.
      Since the action of Botulinum toxin is limited to 2-6 months, new neural
      collaterals are formed and neuromuscular conductivity is reestablished which in
      the end once again develops a muscular spasm. This leads to a conclusion that
      botulinum toxin should again be applied into spastic muscles. It is very
      important for good effect of Botulinum toxin to set the goals of the therapy in
      advance. The goals include improvement of a function, prevention of contractions
      and deformities, ease of care and decrease of pain for children with cerebral
      palsy. After application of botulinum toxin, it is necessary to perform adequate
      and intensive physical treatment with regular monitoring of effects. This work
      shows a case of a boy with spastic form of cerebral palsy. After being
      rehabilitated using Vojta therapy and Bobath concept and the conduct of certain
      physical procedures, botulinum toxin is administered into his lower limbs'
      muscles and kinesiotherapy is intensified. After the administration of botulinum
      toxin significant functional improvement is noted.

PMID- 18039198
TI  - Gastric pull-up reconstruction for the hypopharyngeal and cervical esophageal
      carcinoma in small thoracic unit.
AB  - The objective of this article is to review results of one surgical team for
      gastric pull-up reconstruction for carcinoma of the hypopharynx and cervical
      esophagus after pharyngolaryngo-esophagectomy in small thoracic unit. Between
      July, 2004 and December 2005, four patients underwent pharyngolaryngo
      esophagectomy and gastric pull-up reconstruction for carcinoma of hypopharynx and
      esophagus. There were three female and one male patient with average age at the
      time of surgery 47 years. The study analyzed complications and mortality in early
      postoperative period after resections of the carcinoma. Squamous cell cancer in
      all patients was confirmed. There was no in-hospital mortality and non-fatal
      complications were occurred in 3 patients. It was recorded two year survival for
      two patients. Pharyngolaryngo-esophagectomy and gastric pull-up reconstruction
      can be performed for the patients with carcinoma of the hypopharynx and cervical
      esophagus with an acceptable operative mortality and morbidity rate even in small
      thoracic unit. Long term survival despite good early postoperative results still
      remains poor.

PMID- 18039199
TI  - Trend of Balkan endemic nephropathy patients on renal replacement therapy in
      Bosnia from 2003 through 2005.
AB  - The aim of this study is to evaluate epidemiological status of Balkan endemic
      nephropathy (BEN) patients on renal replacement therapy (RRT) in Bosnia from 2003
      through 2005. Incidence and prevalence rates of BEN, diabetes mellitus (DM) and
      RRT population and proportion of BEN RRT population in total RRT population were
      tracked in renal units covering the entire BEN endemic region in Bosnia. BEN
      incidence and prevalence rates were 52; 34;48 and 262; 265, 292, respectively. DM
      incidence and prevalence rates were 7; 13; 8 and 20; 28; 33, respectively. Total
      RRT population incidence and prevalence rates were 89; 82; 79 and 424; 436; 473,
      respectively. Proportions of incident BEN RRT population in incident total RRT
      population and proportions of incident BEN RRT population in incident total RRT
      population when incident diabetics were subtracted from incident total RRT
      population were 0.58; 0.41; 0.61, and 0.63; 0.49; 0.67; respectively. Proportions
      of prevalent BEN RRT population in prevalent total RRT population and proportions
      of prevalent BEN RRT population in prevalent total RRT population when prevalent
      diabetics were subtracted from prevalent total RRT population were 0.62; 0.61;
      0.62, and 0.65; 0.65; 0.66, respectively. Trend of BEN RRT population was stable
      in Bosnia from 2003 through 2005.

PMID- 18039200
TI  - Fixed combination lisinopril plus hydro-chlorothiazide in the treatment of
      essential arterial hypertension: an opened, multi-centre, prospective clinical
      trial.
AB  - The aim of this trial was to examine the efficacy and safety of antihypertensive
      fixed combination lisinopril plus hydrochlorothiazide (Lopril H, Bosnalijek dd)
      in the treatment of essential arterial hypertension. In our trial we included 297
      patients, aged 54.65+/-9.6 years, with treated or untreated hypertension and with
      high risk of cardiac events, in an opened trial of therapy based on lisinopril
      plus hydrochlorothiazide. Upon the examination by physicians, patients were
      divided into three groups in accordance with European Society of Cardiology
      guidelines for the management of arterial hypertension. Patients from five
      European countries were followed up for a period of 12 weeks. Duration of
      treatment was 12 weeks. We adjusted daily doses of lisinopril plus
      hydrochlorothiazide after every clinical examination and recorded adverse effects
      of drugs. After 12 weeks of treatment, 288 patients (96%) were evaluated for
      efficacy, tolerability and safety. In almost 81.5% patients with mild, moderate
      and severe hypertension, we recorded a reduction in blood pressure to
      approximately normal values SBP and DBP (140/90 mmHg). Drug-related side-effects
      occurred in 11 patients (3.66%). The most commonly reported adverse effects
      associated with lisinopril plus hydrochlorothiazide were cough (5) and dry mouth
      (5). This research has proved good efficacy of fixed combination lisinopril plus
      hydrochlorothiazide with more than 97% patients. Based on subjective estimation
      by patients: this drug improved quality of life in all cases.

PMID- 18039201
TI  - Guidelines for the antiviral therapy of hepatitis C virus carriers with normal
      serum aminotransferase based on platelet counts.
AB  - AIM: We aimed to identify the candidates for antiviral therapy, among patients
      who are hepatitis C virus (HCV) carriers with normal serum aminotransferase
      (ALT), focused on the inhibition of hepatocellular carcinoma (HCC). METHODS: Four
      hundred and sixty-four HCV carriers with normal serum ALT and 129 HCV carriers
      with persistently normal ALT (PNALT) and platelet (PLT) counts >/=150 000/muL who
      received liver biopsies were enrolled. HCV carriers with normal serum ALT were
      divided into four groups according to their ALT levels (</=30 U/L or 31-40 U/L)
      and PLT counts (>/=150 000/muL or <150 000/muL). RESULTS: In 129 HCV carriers
      with PNALT, the rate of progression of fibrosis stage was 0.05/year and no HCC
      was detected during the follow up for 10 years. Approximately 20% of patients
      with ALT </=40 U/L and PLT counts >/=150 000/muLwere at stage F2-3; however,
      approximately 50% of patients with ALT </= 40 U/L and PLT counts <150 000/muL
      were at stage F2-4. An algorithm for the management of HCV carriers with normal
      serum ALT was advocated based on ALT and PLT counts. CONCLUSION: The combination
      of ALT and PLT counts is useful for evaluating the fibrosis stage in HCV carriers
      with normal serum ALT. Most patients with PLT counts <150 000/muL are candidates
      for antiviral therapy, especially those with ALT levels >/=31 U/L when we focus
      on the inhibition of the development of HCC.

PMID- 18039202
TI  - Development of evidence-based clinical guidelines for the diagnosis and treatment
      of hepatocellular carcinoma in Japan.
AB  - The Clinical Practice Guidelines for Hepatocellular Carcinoma (HCC), the first
      evidence-based guidelines for the treatment of HCC in Japan, were compiled by an
      expert panel supported by the Japanese Ministry of Health, Labour, and Welfare.
      This set of guidelines covers six research fields: prevention, diagnosis and
      surveillance, surgery, chemotherapy, transarterial chemoembolization, and
      percutaneous local ablation therapy. A systematic review of the English medical
      literature on HCC was performed, and a total of 7192 publications were extracted,
      mainly from MEDLINE (1966-2002). After the second selection, 334 articles were
      adopted for the guidelines to form 58 pairs of research questions and
      recommendations. For the users' convenience, practical algorithms for the
      surveillance and treatment of HCC were also created, which were based on evidence
      from the selected articles forthe guidelines and modified according to the
      current status of medical practice in Japan, where liver resection for HCC is
      regarded as safe with less than 1% mortality and cadaveric donors for liver
      transplantation are extremely difficult to obtain. The formation of the
      guidelines and the outline of their contents are described. The Japanese HCC
      guidelines may be useful in decision making at every clinical step, both for
      patients and physicians. Although the main users of these guidelines are assumed
      to be Japanese physicians, the accumulated evidence and interpretation in the
      guidelines may attract universal attention.

PMID- 18039203
TI  - Erratum.

PMID- 18039204
TI  - Surgery for cardiac valves and aortic root without cardioplegic arrest ("beating
      heart"): experience with a new method of myocardial perfusion.
AB  - Simultaneous antegrade/retrograde warm blood perfusion with a beating heart has
      not been previously reported as a mean of protecting hypertrophied hearts in
      cardiac valve and aortic root surgeries. Similarly, beating heart mitral valve
      surgery via the trans-septal approach with the aorta unclamped, is a novel
      technique. We, herein, report a series of 346 patients with a variety of cardiac
      pathologies who were operated upon utilizing a new modality of myocardial
      perfusion. Among this group of patients, there were 55 patients who were
      diagnosed with endocarditis of one or more valves. These patients were excluded
      from this series of patients. Mean age was 59 +/- 12, and there were 196 (67.3%)
      males and 95 (32.7%) females. There were six aortic root procedures, 90 mitral
      valve replacements (MVR), 46 mitral valve repairs, 20 MVR+ coronary artery bypass
      grafting (CABG), 28 tricuspid valve repairs, 106 aortic valve replacements (AVR),
      17 AVR+CABG, and 8 AVR/MVR. Crude mortality for the group was 20 of 291 (6.8%).
      Intra-aortic balloon pump utilization at time of weaning from cardiopulmonary
      bypass was 6/291 (2.06%), and re-operation for bleeding was needed in 12 of 291
      (4.1%) patients. Postoperative stroke occurred in 4 of 291 (1.3%) patients. In
      these patients, the clinical diagnosis of stroke was made prior to surgery. This
      initial experience with this new method of myocardial perfusion indicates that
      results are at least comparable, if not superior, to conventional techniques
      utilizing intermittent cold blood cardioplegia.

PMID- 18039205
TI  - Improvement of outcomes after coronary artery bypass II: a randomized trial
      comparing intraoperative high versus customized mean arterial pressure.
AB  - BACKGROUND AND AIM OF THE STUDY: The objective of this randomized trial was to
      compare the efficacy of two strategies of hemodynamic management during
      cardiopulmonary bypass (CPB) on morbidity, mortality, cognitive complications and
      deterioration in functional status. METHODS: Patients scheduled to undergo
      primary elective CABG were eligible. In one group, mean arterial pressure target
      during CPB was 80 mmHg ("high" MAP group); in the other group, MAP target was
      determined by patients' pre-bypass MAP ("custom" MAP group). The principal
      outcomes were mortality, major neurologic or cardiac complications, cognitive
      complications or deterioration in functional status. RESULTS: Of 412 enrolled
      patients, 36% were women, with overall mean age of 64.7 +/- 12.3 years. Duration
      of bypass was identical for the two randomization groups. Overall complication
      rates were similar: 16.5% of the high group and 14.6% of the custom group
      experienced one or more neurologic, cardiac or cognitive complications. When only
      cardiac and neurologic morbidity and mortality were considered, the rates were
      11.7% and 12.6%, in the high and custom groups, respectively. The aggregate
      outcome rate, including functional deterioration, was 31.6% in the high group and
      29.6% in the custom group. CONCLUSIONS: There were no statistically significant
      differences between the high MAP group and the custom MAP group for the combined
      outcome of mortality cardiac, neurologic or cognitive complications, and
      deterioration in the quality of life.

PMID- 18039206
TI  - Aortic valve repair and root preservation by remodeling, reimplantation, and
      tailoring: technical aspects and early outcome.
AB  - OBJECTIVES: Evaluate aortic root preserving/sparing procedures for various
      pathologies associated with ascending aortic aneurysms, including aortic valve
      regurgitation. METHODS: From the end of 1990 through end of 2004, 388 patients
      had aortic root preserving procedures (reimplantation 72, remodeling 77,
      tailoring 239) +/- leaflet repair. Preoperatively, in-house grade aortic
      regurgitation was 1(+) in 58, 2(+) in 110, 3(+) in 101, and 4(+) in 66.
      Concurrent leaflet repairs were done in 197 (50.8%, Cabrol/Trusler commissure
      stitch 158, leaflet plication 36, supracommissure stitch 42, leaflet resection
      and repair 16, perforation repair 18, and debridement 11). Additional procedures
      included arch repair in 227 (58%), coronary bypass in 83 (21.4%), elephant trunk
      in 33 (8.5%), and minimally invasive approach in 30 (7.7%). Pathologies included
      dissection in 140 (36%; 86 acute), Marfan syndrome in 39 (10%), bicuspid valve in
      78 (20%), and degenerative aneurysm in 142 (36.6%). The CLASS (Commissure,
      Leaflet, Annulus, Sinuses, Sinotubular) evaluation schema is described that is
      used for selecting either reimplantation, remodeling, or tailoring of the aortic
      root according to underlying pathology. RESULTS: Hospital survival was 97.4%
      (378/388) and stroke occurred in 4.6% (18/388, four permanent, [1%]). On
      postoperative echocardiography, patients had either no (0) or 1(+) regurgitation
      (1(+)= 98);13 (3.4%) had 2(+). Three patients (1%) required reoperation for
      aortic valve failure before discharge (two tailoring, one remodeling).
      CONCLUSIONS: Excellent early results can be achieved by aortic root preserving
      procedures and concurrent aortic valve leaflet repairs when appropriately
      selected for a diverse class of pathologies.

PMID- 18039207
TI  - Mild or moderate ischemic mitral regurgitation in patients undergoing off-pump
      coronary artery bypass grafting.
AB  - BACKGROUND: There has been a debate, whether mild or moderate ischemic mitral
      regurgitation (IMR) should be repaired at the time of coronary bypass surgery. We
      assessed the early and midterm outcomes of patients with mild or moderate IMR who
      underwent isolated off-pump coronary artery bypass grafting (OPCAB). METHODS: We
      retrospectively reviewed records of 602 patients who underwent OPCAB between
      April 2001 and July 2004. Of those, 96 patients had mild or moderate MR (IMR
      group), and 506 had none or trivial MR (no IMR group). Preoperative and
      postoperative characteristics were compared between the groups. Furthermore,
      fates of grade of MR and functional status were investigated in patients with
      IMR. RESULTS: The preoperative mean New York Heart Association (NYHA) classes
      were 2.7 +/- 1.0 and 2.4 +/- 0.9 in the IMR and no IMR groups, respectively (p <
      0.01). Operative mortality was similar between groups (1.0% in the IMR group and
      0.4% in no IMR group, p = 0.41). The cumulative survival rate for the IMR group
      was 93.7% at 1 year and 90.1% at 4 years. The mean NYHA class was 1.1 +/- 0.4 (p
      < 0.0001) at 28.8 +/- 11.4 months after operation for the IMR group. The mean
      grade of mitral regurgitation diminished (from 2.2 +/- 0.4 to 1.1 +/- 0.6, p <
      0.0001) soon after operation in patients with IMR, and remained so (1.1 +/- 0.8,
      p < 0.0001) during the follow-up period. CONCLUSIONS: Mild or moderate IMR could
      be improved with isolated OPCAB. The early and midterm functional outcomes of
      these patients were favorable.

PMID- 18039208
TI  - Impact of valve prosthesis-patient mismatch on intermediate-term outcome and
      regression of left ventricular mass following aortic valve replacement with
      mechanical prosthesis.
AB  - BACKGROUND: The impact of aortic valve replacement (AVR) with prosthesis-patient
      mismatch (PPM) on intermediate-term outcome and left ventricular mass (LVM)
      regression in patients with aortic stenosis (AS) was investigated. METHODS: One
      hundred fifty patients with AS (87 pure stenosis and 63 combined stenosis and
      regurgitation) were classified into a PPM group (n = 34, indexed effective
      orifice area (EOAI) >0.65 cm(2)/m(2) and < or =0.85 cm(2)/m(2); moderate PPM) and
      a non-PPM group (n = 116, EOAI > 0.85). Mean age, mean and peak aortic pressure
      gradient (PG) were not different between the groups (PPM, 99.7 +/- 37.2 and 54.9
      +/- 23.2 mmHg; non-PPM, 95.9 +/- 29.2 and 54.4 +/- 16.0 mmHg). The absolute and
      relative regression in indexed left ventricular mass (LVMI) was estimated by
      preoperative and postoperative echocardiography (n = 98). RESULTS: Twelve
      patients died (valve-related death in 7) during 5 years of follow-up. Comparing
      the PPM and non-PPM groups, overall survival (78.7% vs. 87.8%) and survival free
      from valve-related death (96.8% vs. 92.1%) were not significantly different. New
      York Heart Association (NYHA) functional class improved in all patients and there
      were no patients in class III or IV. The postoperative mean PG was 14.6 +/- 6.1
      mmHg in the PPM group and 9.4 +/- 3.8 mmHg in the non-PPM group (p = 0.0005),
      with an inverse correlation (r = -0.48, p < 0.0001) between EOAI and the
      postoperative mean PG. However, there was no significant difference in the
      absolute and relative LVMI regression between the two groups. Multiple linear
      regression analysis was performed and higher preoperative LVMI and mean aortic PG
      were independent predictors of greater LVMI regression after AVR. CONCLUSIONS:
      Moderate PPM does not appear to alter LVMI regression, NYHA class, or
      intermediate-term outcome in AS patients undergoing AVR with mechanical
      prostheses. In multivariate analysis, preoperative LVMI and mean aortic PG were
      important independent predictors of LVMI regression.

PMID- 18039209
TI  - Clopidogrel is safe early after on- and off-pump coronary artery bypass surgery.
AB  - OBJECTIVES: The goal of this study was to assess the safety of early
      postoperative clopidogrel in patients undergoing on-pump and off-pump coronary
      artery bypass graft (CABG) surgery. METHODS: Observational data was collected
      prospectively on 117 consecutive patients who underwent primary multivessel CABG
      between July 2002 and June 2005. When postoperative chest tube drainage was < or
      =50 cc/h for 2 hours, daily clopidogrel (75 mg) and aspirin (81 mg) were
      initiated in 63 patients (Group CA) versus aspirin alone in 54 patients (Group
      A). Demographic, operative, and postoperative data were compared with linear
      regression and propensity-score based techniques. RESULTS: Total chest tube
      drainage and drainage after patients received antiplatelet agents were equivalent
      between groups. Clopidogrel administration did not increase the incidence of
      reexploration, transfusion, or the quantity of blood products transfused. No
      mortality or extrathoracic bleeding occurred in either group, and there were no
      differences in the incidence of adverse myocardial events or hospital length of
      stay. CONCLUSIONS: When given according to a predefined postoperative protocol,
      early postoperative clopidogrel can safely be administered in on-pump and off
      pump CABG patients, without increasing the risk of bleeding complications.
      Evaluation of the benefits of clopidogrel therapy early after CABG in a
      randomized setting is ongoing.

PMID- 18039211
TI  - Transposition of arch vessels and endovascular stenting of saccular aneurysm of
      distal arch--a case report.
AB  - Endovascular repair of thoracic aneurysms has emerged as an attractive
      alternative especially in high-risk patients. However, the aortic curvature and
      potential coverage of the epiaortic vessels limit the use of stent-grafts in
      aneurysms located in the aortic arch. We report a case with a saccular aneurysm
      in the distal arch and proximal descending aorta, where we have transposed the
      epiaortic vessels to gain a longer proximal neck in the aortic arch to safely
      deploy an endovascular stent.

PMID- 18039210
TI  - Venous gas embolization during endoscopic vein harvesting for coronary artery
      revascularization: a life-threatening event.
AB  - A case of massive gas embolization during endoscopic vein harvesting is
      presented. This potentially life-threatening condition should be promptly
      diagnosed and treated. A brief review of the current literature is presented.

PMID- 18039212
TI  - Mitral valve replacement for a severely calcified mitral annulus.
AB  - We herein describe a surgical technique in a mitral valve replacement for a
      hemodialysis patient presenting with mitral valve stenosis and severe mitral
      annular calcification. Mitral annular calcification extending to the left
      ventricular myocardium was resected using a cavitron ultrasonic surgical
      aspirator (CUSA) to make a flat plane from the left atrium to the left ventricle.
      An autologous pericardium was secured to the posterior left ventricular wall and
      to the left atrial wall covering the mitral annulus for annular reconstruction.
      In the posterior mitral annulus, the prosthetic valve was fixed onto this
      pericardial patch. After the operation, the patient recovered well without any
      embolic complications. The prosthetic valve functions normally without any
      perivalvular leakage. Decalcification using the CUSA and the annular
      reconstruction with a pericardial patch is therefore indicated in valve
      replacement for patients with severe mitral annular calcification.

PMID- 18039213
TI  - A safe technique of exposing of a "hidden" left anterior descending artery.
AB  - We describe a safe, easy, and fast technique of exposing the left anterior
      descending artery (LAD), when this is embedded under the myocardium or excessive
      epicardial fat tissue, during coronary artery bypass grafting (CABG) or off-pump
      coronary artery bypass (OPCAB). The vessel is opened as distal as possible, then
      a fine intravascular probe is introduced retrogradely. Through palpation of the
      tip, the course of LAD is confined together with the site of distal anastomosis
      formation. The suggested technique minimizes the risk of injuring the vessel or
      ventricles, reduces the ischemia-time, and allows the performance of anastomosis
      as paroximal as possible in the cases of OPCAB with embedded LAD.

PMID- 18039215
TI  - Hybrid approach facilitates use of a minimized CPB circuit and transfusion free
      surgery in an extended Norwood stage II procedure.
AB  - Intraoperative stent implantation into a stenotic left pulmonary artery branch
      and surgical creation of a bidirectional Glenn anastomosis resulted in avoidance
      of aortic cross-clamping and transection of the aorta for surgical patching of
      the pulmonary artery. The hybrid approach thereby reduced the complexity of the
      surgical procedure, facilitated the use of a minimized cardiopulmonary bypass
      circuit, reduced the degree of hemodilution and blood trauma and resulted in
      transfusion-free surgery and excellent clinical outcome in an 11 kg child.

PMID- 18039216
TI  - Coronary bypass surgery in kawasaki disease in a four-year-old patient: case
      report.
AB  - Kawasaki disease is an acute vasculitis syndrome of unknown etiology that mainly
      affects small and medium-sized arteries, particularly the coronary arteries. This
      disease is rarely seen in infants and young people in Turkey. In this short
      report, we present a four-year-old patient who has Kawasaki disease associated
      with coronary artery aneurysm and underwent coronary bypass grafting.

PMID- 18039217
TI  - Primary malignant fibrous histiocytoma of the heart with skeletal muscles
      metastases.
AB  - Malignant fibrous histiocytoma is an extremely rare primary malignant tumor of
      the heart. It is usually diagnosed when it is locally aggressive or has already
      metastasized. The prognosis is poor with an average survival time of one year. We
      report a case of recurrent left atrial malignant fibrous histiocytoma initially
      misdiagnosed as myxoma. The patient underwent repeated surgical resections
      followed by chemotherapy. Despite adjuvant chemotherapy, 18 months after initial
      diagnosis, definitive tumor relapse in left atrium was diagnosed. This is the
      48th case of primary cardiac fibrous malignant histiocytoma reported in the
      literature.

PMID- 18039218
TI  - Trans-aortic repair of a sinus of valsalva aneurysm.
AB  - Sinus of Valsalva aneurysms are rare and vary in their presentation and approach
      of surgical repair. We report on a case of isolated right sinus of Valsalva
      aneurysm that underwent successful excision and patch repair with individual
      sutures placed through the annulus of the aortic valve.

PMID- 18039219
TI  - A case of pneumopericardium following endomyocardial biopsy.
AB  - Pneumopericardium is a very rare condition, less common than isolated
      pneumothorax or pneumomediastinum. Since it can occasionally cause pericardial
      tamponade, prompt recognition and treatment of this condition is lifesaving. Up
      to now only one case of isolated pneumopericardium after endomyocardial biopsy
      has been reported in a two-month boy with a dilated cardiomyopathy of unknown
      origin. In the current case, we report a 25-year-old man who underwent orthotopic
      heart transplantation three years ago in whom isolated pneumopericardium occurred
      following endomyocardial biopsy performed via right internal jugular vein.

PMID- 18039220
TI  - Effect of epicardial fat on ablation performance: a three-energy source
      comparison.
AB  - OBJECTIVES: To investigate the effect of epicardial fat on surgical atrial
      fibrillation ablation performance using an in vitro model. Two tissue models were
      employed to investigate standard penetration and maximal lesion depth performance
      of bipolar radiofrequency (RF), microwave, and laser energy sources. METHODS:
      Ventricular veal tissue was utilized in various thicknesses (3 mm, 5 mm, 7 mm, 15
      mm). Epicardial fat was modeled by layering porcine fat (1 mm, 2 mm and 4 mm) on
      moistened tissue. In each group, 8 to 10 lesions were created. Post ablation,
      tissue samples were sectioned and ablation depth of each myocardial section
      measured using 1% tetrazolium tetrachloride dye solution. RESULTS: The laser
      energy source produced nearly 100% transmural lesions in almost all study groups
      irrespective of myocardium thickness and fat thickness. The microwave device
      maintained transmurality in all 3-mm and most 5-mm myocardium trials but fell to
      near zero with all 7-mm myocardium trials. The bipolar RF maintained
      transmurality only when no fat was applied. In the maximal lesion depth models,
      the laser was capable of producing lesions >8 mm with no fat and >6 mm with
      either 2 mm or 4 mm of fat present. The microwave produced lesions in the no fat
      (>6 mm) and 2-mm (>4 mm) fat group. The bipolar RF produced 83% transmurality
      with no fat and zero percent transmurality with 2 mm of fat present. CONCLUSIONS:
      Epicardial fat can severely limit transmurality in energy sources that utilize
      conductive heating. Laser energy was uniformly superior at producing both
      transmural and deep lesions irrespective of the presence of fat.

PMID- 18039221
TI  - Emergency endovascular stent graft repair of aorto-bronchial fistulas
      postcoarctation repair.
AB  - Cardiovascular complications following coarctation repair include aorto bronchial
      fistulas (ABF) which if untreated are invariably fatal. Reoperative surgery is
      associated with considerable mortality and morbidity. Endovascular stent
      aortoplasty provides a relatively new and viable alternative. Two cases of ABF
      post coarctation repair that presented with life threatening haemoptysis are
      discussed. Endovascular repair appears safe and feasible in an emergency and may
      become the preferred treatment modality in such cases.

PMID- 18039222
TI  - Surgical intervention to remove an entrapped fractured guidewire during
      angioplasty.
AB  - Intra-coronary entrapment of angioplasty hardware is a rare complication of
      coronary intervention. Such complication is potentially dangerous. We present two
      cases of an entrapped fractured guidewire during angioplasty. They were managed
      by urgent coronary bypass.

PMID- 18039223
TI  - Mechanical prosthetic valve dysfunction causing pulsus alternans leading to
      intermittent electromechanical dissociation: a case report and literature review.
AB  - We describe a case of electromechanical dissociation (EMD) in a 62-year-old
      female patient following insertion of a Medtronic Hall mitral valve prosthesis.
      She initially developed pulsus alternans which led, over a few hours, to
      intermittent electromechanical dissociation. Clinical and echocardiographic
      findings are described. Emergency surgical intervention revealed a piece of
      chorda wedged between the disc occluder and the valve ring. This case illustrates
      clinical and Doppler echocardiographic features associated with a rare
      presentation of an unusual perioperative complication of prosthetic mitral valve
      dysfunction. We have also included a brief review of related literature.

PMID- 18039225
TI  - Surgical options for refractory ventricular tachycardia.
AB  - Ventricular tachycardia (VT) is most often treated with antiarrhythmic drug
      therapy. When standard drugs fail, percutaneous, endocardial ablation guided by
      electroanatomic mapping is usually curative. Occasionally, these options are
      either unsuccessful or are not feasible, and surgical ablation is required.
      Surgical ablation of VT employs electroanatomic mapping and a variety of ablation
      strategies and technologies. The specific approach (endocardial vs. epicardial,
      beating heart vs. arrested) and ablation device must be tailored to the patient's
      anatomy and presentation. We present three cases to illustrate the range of
      surgical options available for ablation of VT arising from different anatomic
      foci.

PMID- 18039226
TI  - Persistent left SVC with absent right SVC: a rare anomaly.
AB  - A persistent left superior vena cava is an anomaly found in association with many
      congenital heart disorders. However its presence along with absence of the right
      superior vena cava is a very rare congenital anomaly. This anomaly has
      implications in various interventional procedures and in cardiac surgery. We
      present here a case with absence of the right SVC and a persistent left SVC found
      in association with an ostium secundum atrial septal defect.

PMID- 18039227
TI  - Atrial septal occluder device surveillance using 64 multi-slice computed
      tomography.

PMID- 18039229
TI  - Toxicity of chronic paracetamol ingestion.

PMID- 18039230
TI  - Alcohol, drugs, and the adolescent brain.

PMID- 18039231
TI  - Diagnosing paediatric multiple sclerosis versus acute disseminated
      encephalomyelitis.

PMID- 18039232
TI  - Localized and distant actions of BTX-A injections.

PMID- 18039233
TI  - Intracranial pressure measurement in children.

PMID- 18039234
TI  - Early relapse risk after a first CNS inflammatory demyelination episode:
      examining international consensus definitions.
AB  - The International Pediatric Multiple Sclerosis Study Group (IPMS) has recently
      proposed consensus definitions for paediatric multiple sclerosis (MS) and related
      disorders. The term 'acute disseminated encephalomyelitis' (ADEM) has been used
      previously to describe any monophasic episode of disseminated demyelination. The
      study group now propose that ADEM must be multifocal, polysymptomatic, and
      include encephalopathy (as an essential requirement). An alternative diagnosis
      for a first acute inflammatory event is 'clinically isolated syndrome' (CIS). A
      CIS event may be either monofocal (such as isolated optic neuritis) or
      multifocal, but cannot include encephalopathy. As with adults, children with two
      or more discrete demyelinating events separated in time and space meet criteria
      for MS. In children with MS, the demyelination events must not meet ADEM
      criteria. To test the usefulness of these new criteria, a new cohort of 40
      patients (18 males, 22 females; mean age 8 y [SD 4 y 4 mo]) with central nervous
      system (CNS) demyelination were studied. Using IPMS definitions, the presenting
      diagnosis was ADEM in 12 patients and CIS in 28 patients. At presentation,
      patients with CIS were more likely to have intrathecal synthesis of oligoclonal
      bands and fulfil KIDMUS MS magnetic resonance imaging criteria, compared with
      patients with ADEM (p<0.025). Patients were followed-up for a mean of 2 years 2
      months. Only one of 12 patients with ADEM went on to develop MS during the study
      period, whereas 13 of 28 patients with CIS relapsed and fulfilled a diagnosis of
      MS (p<0.025). The new diagnostic criteria for ADEM may be criticized for being
      overly restrictive (particularly with encephalopathy being an essential
      criterion), and it is suspected that many practising physicians will be of the
      opinion that these new criteria will underdiagnose ADEM, and overdiagnose MS at
      the expense of multiphasic ADEM. However, it is hoped that these new criteria may
      improve prognostic specificity and provide uniformity to future paediatric CNS
      demyelination research.

PMID- 18039235
TI  - Neurological complications of cardio-facio-cutaneous syndrome.
AB  - Cardio-facio-cutaneous syndrome (CFC) is a multiple congenital anomaly disorder
      characterized by craniofacial dysmorphia, ectodermal abnormalities, congenital
      heart defects, and developmental and growth delay. Neurological complications
      associated with CFC remain to be clearly defined. Recent discovery of causative
      mutations in genes of the MAPK pathway (BRAF, MEK1, and MEK2) now permit accurate
      molecular diagnosis of CFC. The aim of the study was to characterize neurological
      features of participants with molecularly-confirmed CFC. Medical records, and
      laboratory and imaging data were reviewed for 39 mutation-positive individuals
      with CFC. Participants with a clinical diagnosis of CFC but a negative result on
      mutation screening of the BRAF, MEK1, and MEK2 genes were excluded from the
      study. Mean age of participants was 9 years 4 months (range 18 mo-24 y); there
      were 24 females and 15 males. Mutations in B RA F were present in 32
      participants, MEK1 in five, and MEK2 in two participants. Hypotonia, motor delay,
      speech delay, and learning disability were universally present in this cohort.
      Macrocephaly was present in 13 participants, ptosis in 11, strabismus in 14, and
      nystagmus in 11 of the 22 participants who underwent a neurological exam.
      Corticospinal tract findings were present in seven participants. Ventriculomegaly
      or hydrocephalus was present in 14 of 32 participants who underwent brain
      imaging. Other findings on magnetic resonance imaging included prominent Virchow
      Robin spaces (n=6), abnormal myelination (n=4), and structural anomalies (n=5).
      Seizures were present in 15 participants. No specific genotype-phenotype
      correlation was observed.

PMID- 18039236
TI  - Feasibility of robotic-assisted locomotor training in children with central gait
      impairment.
AB  - Intensive, task-specific training enabled by a driven gait orthosis (DGO) may be
      a cost-effective means of improving walking performance in children. A paediatric
      DGO has recently been developed. This study was the first paediatric trial aimed
      to determine the feasibility of robotic-assisted treadmill training in children
      with central gait impairment (n=26; 11 females, 15 males; mean age 10 y 1 mo [SD
      4 y]; range 5 y 2 mo-19 y 5 mo). Diagnoses of the study group included cerebral
      palsy (n=19; Gross Motor Function Classification System Levels I-IV), traumatic
      brain injury (n=1), Guillain-Barre syndrome (n=2), incomplete paraplegia (n=2),
      and haemorrhagic shock (n=1), and encephalopathy (n=1). Sixteen children were in
      patients and 10 were outpatients. Twenty-four of the 26 patients completed the
      training which consisted of a mean of 19 sessions (SD 2.2; range 13-21) in the in
      patient group and 12 sessions (SD 1.0; range 10-13) in the outpatient group. Gait
      speed and 6-Minute Walking Test increased significantly (p<0.01). Functional
      Ambulation Categories and Standing dimension (in-patient group p<0.01; outpatient
      group p<0.05) of the Gross Motor Function Measure improved significantly. DGO
      training was successfully integrated into the rehabilitation programme and
      findings suggest an improvement of locomotor performance.

PMID- 18039237
TI  - Increased efficacy and decreased systemic-effects of botulinum toxin A injection
      after active or passive muscle manipulation.
AB  - The effect of physical manipulation on the outcome of neurotoxin (NT) injection
      was studied in a rat tibialis anterior (TA) model system where dorsiflexion
      torque could be measured precisely. After determination of initial torque, all
      rats received a one-time botulinum toxin A (BTX-A) injection (dose 6.0 units/kg
      in a volume of 100 microL) into the TA midbelly. Four experimental groups were
      studied: one group was subjected to BTX-A injection alone (BTX-A only, n=8), one
      was subjected to BTX-A injection followed immediately by 10 isometric
      contractions (ISO; n=9), and the third was subjected to BTX-A followed
      immediately by 10 muscle passive stretch/release cycles (PS; n=10). After 1
      month, maximum dorsiflexion torque of the injected and contralateral legs was
      determined followed by quantification of TA fiber area. Post-injection torque was
      significantly reduced by around 80% in all NT-treated extremities 1 month after
      injection (p<0.05). While all NT-treated extremities demonstrated a significant
      torque decrease relative to their pre-injection levels, ISO and PS groups
      demonstrated significantly lower torques compared with the BTX-A only group which
      received no physical manipulation (p<0.05) indicating greater efficacy. Perhaps
      even more surprising was that the ISO and PS groups both demonstrated a
      significantly smaller contralateral effect compared with the BTX-A only group
      that received no manipulation (p<0.05) indicating a decreased systemic-effect.
      Muscle fiber size generally correlated with dorsiflexion torque. These data
      demonstrate that both neuromuscular activity (seen in the ISO group) and muscle
      movement (seen in the PS group) increased the efficacy of BTX-A and decreased the
      systemic side effects.

PMID- 18039238
TI  - Psychometric characteristics of the Neonatal Oral-Motor Assessment Scale in
      healthy preterm infants.
AB  - We examined the reliability, validity, and responsiveness of the Neonatal Oral
      Motor Assessment Scale (NOMAS) in healthy preterm infants. Feeding records of 147
      infants (71 males, 76 females; gestational age [GA] <or= 36 wks), taken from the
      day bottle-feeding was initiated to the day the infants were discharged, were
      used to examine the psychometric properties of the normal and disorganized
      categories of the NOMAS. The infants, with or without experience of
      breastfeeding, were all fed by bottle, with either formula and/or breast milk. GA
      ranged from 24 to 35.9 weeks (mean 29.7 wks, SD 2.7) and birthweight ranged from
      470 g to 2570 g (mean 1251.1g, SD 425.9). Postmenstrual age (PMA) at the starting
      point of bottle-feeding ranged from 29.4 to 40.1 weeks (mean 33.8 wks, SD 1.7).
      We found that the NOMAS had satisfactory internal consistency (Cronbach's alpha
      >0.70) in the normal category for 32 to 35 weeks'PMA. Moderate correlations were
      found between scores on the NOMAS and feeding performance for all age groups
      except for PMA of >or= 36 weeks (absolute Spearman's r(s)=0.51-0.69), indicating
      acceptable convergent validity. The NOMAS demonstrated moderate responsiveness to
      changes in oral-motor skills in every 2-week period, ranging from 32 to 36
      weeks'PMA (standard response mean greater than 0.5). This study demonstrated that
      the normal and disorganized categories of the NOMAS are useful, with acceptable
      psychometric properties, in assessing oral-motor function in preterm infants aged
      32 to 35 weeks'PMA. Future research on infants with abnormal oral-motor skills is
      needed to further validate psychometric properties of the dysfunction category of
      the NOMAS.

PMID- 18039239
TI  - Developmental coordination disorder in children with attention-deficit
      hyperactivity disorder and physical therapy intervention.
AB  - Although physical therapy (PT) is effective in improving motor function in
      children with developmental coordination disorder (DCD), insufficient data are
      available on the impact of this intervention in children with combined attention
      deficit-hyperactivity disorder (ADHD) and DCD. This prospective study aimed to
      establish the prevalence of DCD among a cohort of patients with ADHD,
      characterize the motor impairment, identify additional comorbidities, and
      determine the role of PT intervention on these patients. DCD was detected in
      55.2% of 96 consecutive children with ADHD (81 males, 15 females), mostly among
      patients with the inattentive type (64.3% compared with 11% of those with the
      hyperactive/impulsive type, p<0.05). Mean age was 8 years 4 months (SD 2 y).
      Individuals with both ADHD and DCD more often had specific learning disabilities
      (p=0.05) and expressive language deficits (p=0.03) than children with ADHD only.
      Twenty-eight patients with ADHD and DCD randomly received either intensive group
      PT (group A, mean age 9 y 3 mo, SD 2 y 3 mo) or no intervention (group B, mean
      age 9 y 3 mo, SD 2 y 2 mo). PT significantly improved motor performance (assessed
      by the Movement Assessment Battery for Children; p=0.001). In conclusion, DCD is
      common in children with ADHD, particularly of the inattentive type. Patients with
      both ADHD and DCD are more likely to exhibit specific learning disabilities and
      phonological (pronunciation) deficits. Intensive PT intervention has a marked
      impact on the motor performance of these children.

PMID- 18039240
TI  - Children with severe developmental disabilities and behavioral disorders have
      increased special healthcare needs.
AB  - We studied whether children with severe developmental disabilities (SDDs) who
      have a comorbid behavioral disorder also have higher rates of special healthcare
      needs (SHCNs). We used a matched-comparison control group design to establish
      whether SHCNs were higher in children with SDDs with behavioral disorders versus
      children with SDDs without behavioral disorders. Thirty-six children were matched
      for age (mean 12 y 6 mo; range 5 y 2 mo-18 y 8 mo), sex (24 males, 12 females),
      ethnicity (22 non-white), mental retardation level (22 moderate, eight severe,
      six profound), and Diagnostic and Statistical Manual of Mental Disorders, 4th
      edition axis I diagnosis (18 autism spectrum disorder, 10 specified syndrome,
      eight mental retardation not otherwise specified). Measures included the
      Achenbach Child Behavior Checklist, behavioral observation, health status
      examination, and Childhood Health Questionnaire (CHQ). Children with SDDs with
      behavioral disorders had significantly higher levels of SHCN, as measured by the
      CHQ and health status examination. Children with SDDs with behavioral disorders
      had a twofold higher incidence of SHCNs than children with SDDs without
      behavioral disorders. No difference was observed in the number or types of
      prescription medication that children received. The findings suggest that SHCNs
      contribute to the occurrence and/or intensity of behavioral disorders in children
      with SDD and may require interdisciplinary care coordination.

PMID- 18039241
TI  - Encephalopathy with retinitis due to cat-scratch disease.
AB  - Cat-scratch disease is one of several diseases known to be caused by Bartonella
      species. Some infections due to Bartonella resolve spontaneously without
      treatment with antibiotics, but in other cases the disease can be fatal without
      treatment. This case study reports a 7-year-old male who presented with an
      unexplained encephalopathy and unusual retinal findings associated with evidence
      supporting infection by B. henselae. The 7-year-old male presented with a 2-week
      history of general malaise and cervical lymphadenopathy progressing onto fever,
      headache, vomiting, and confusion associated with meningism. Lumbar puncture
      revealed a raised cerebrospinal fluid protein, low glucose, and raised white cell
      count. Abnormal retinal findings and raised antibodies titres to B. quintana
      indicated a diagnosis of cat-scratch disease. He was treated with azithromycin
      orally for 3 weeks and made a complete recovery.

PMID- 18039242
TI  - Measurement of intracranial pressure in children: a critical review of current
      methods.
AB  - Assessment of intracranial pressure (ICP) is essential in the management of acute
      intracranial catastrophe to limit or actively reduce ICP. This article provides
      background information and reviews the current literature on methods of measuring
      ICP in children. Indications for ICP measurement are described for children with
      traumatic brain injury, shunt insertion or malfunction, arachnoid cyst,
      craniosynostosis, and prematurity. Various methods of ICP monitoring are
      detailed: non-invasive, indirect (lumbar puncture, visual-evoked potentials,
      fontanelle compression, and optic nerve sheath), and direct assessment
      (ventricular cannulation, and epidural, subdural, and intraparenchymal devices).
      Normal levels of ICP will depend on the age and position of the child during
      monitoring. This article provides clinical and research-based evidence in this
      area where there is currently limited guidance.

PMID- 18039243
TI  - Systematic review of hyperbaric oxygen therapy for cerebral palsy: the state of
      the evidence.
AB  - A systematic review of the evidence was conducted on the benefits and adverse
      effects of hyperbaric oxygen treatment (HBOT) for cerebral palsy (CP). Studies of
      any HBOT regimen in patients with CP were included except for case reports and
      case series. Electronic databases (e.g. MEDLINE, EMBASE), professional society
      databases, and reference lists were searched to identify studies. Study quality
      was assessed using predefined criteria relevant to the study design. Two
      randomized controlled trials and four observational studies were identified. Best
      evidence came from a randomized controlled trial which found that HBOT at 1.75
      atmospheres (atm) and 1.3 atm of room air resulted in similar improvements in
      motor function (5-6%). Other outcomes also indicated no difference between the
      HBOT and room air. Observational studies reported improvements in motor function
      to a similar degree. Other evidence was insufficient to clarify the benefits
      and/or adverse effects of HBOT for CP. Both HBOT and pressurized room air
      resulted in improvements in motor function compared with baseline. Similar
      improvements were seen in the observational studies. Children undergoing HBOT
      were reported to experience adverse events, including seizures and the need for
      ear pressure equalization tube placement, but the incidence was unclear. Future
      research is needed to determine the efficacy of pressurized room air or non
      pressurized oxygen in equivalent amounts by mask, compared with standard
      treatments.

PMID- 18039244
TI  - The role of magnetic resonance imaging in furthering understanding of the
      pathogenesis of cerebral palsy.

PMID- 18039246
TI  - The use of nurses' and carers' observations in the identification of poststroke
      depression.
AB  - AIM: This paper is a report of a study to determine the accuracy and utility of
      an observational screening tool (Signs of Depression Scale), when rated by nurses
      and carers for detecting depression in patients who have recently had a stroke.
      BACKGROUND: Depression following a stroke is common and adversely affects
      recovery and rehabilitation. Identifying depression when patients have
      communication and cognitive difficulties is especially problematic. Screening
      tools which rely solely on observation may be beneficial in this group. METHOD: A
      cross-sectional study of people admitted with an acute stroke compared a clinical
      diagnosis of depression by a psychiatrist (the gold standard) with the Signs of
      Depression Scale completed by nurses and carers. The agreement between nurses'
      and carers' ratings was also explored. Data were collected over 10 months
      (December 2004-October 2005). FINDINGS: Seventy-one patients were included in the
      study, median age 70 [inter-quartile ranges (IQR) 59-76], including 40 (56.3%)
      males. The psychiatrist classified 25/71 (35.2%) patients as depressed. Using the
      recommended cut-point of 2 or more on the Signs of Depression Scale, the nurse
      and carer respectively rated 27/71 (38.0%) and 18/30 (60.0%) patients as
      potentially depressed. The proportion of patients correctly identified as
      depressed by the test (sensitivity) when rated by nurses was 64%, and the
      proportion of patients not depressed who were correctly identified by the test
      (specificity) was 61%, whereas carers achieved sensitivity 90% and specificity
      35%. The optimal cut-point for carers was higher at 4 or more. Inter-rater
      agreement on the Signs of Depression Scale between nurses and carers was fair
      (ICC = 0.43, 95% CI: 0.09-0.68). CONCLUSION: The Signs of Depression Scale is
      easily completed by clinical staff, although we found the sensitivity when
      completed by nurses to be low. Information from carers shows potential to improve
      screening and it is important for nurses to value the knowledge and skills of
      carers in detecting depression following a stroke. Further refinement of the
      Signs of Depression Scale, with accompanying research, is required.

PMID- 18039245
TI  - Physiological monitoring in acute stroke: a literature review.
AB  - AIM: This paper is a report of a review of the literature that considers how
      physiological parameters may affect outcome after stroke and the implications of
      this evidence for monitoring. BACKGROUND: Throughout the world, the incidence of
      first-ever stroke is approximately 200 per 100,000 people per year [Sudlow et al.
      (1997). Stroke 28, 491]. Stroke is the third most common cause of mortality
      [Sarti et al. (2000). Stroke 31, 1588] and causes 5.54 million deaths worldwide
      [Murray & Lopez (1997). Lancet 349, 268]. Physiological monitoring is considered
      a fundamental component of acute stroke care. Currently, the strength of evidence
      to support its use and identify its components is unclear. Nurse-led
      physiological assessment and subsequent interventions in acute stroke may have
      the potential to improve survival and reduce disability. DATA SOURCES: Online
      bibliographic databases from 1966 to 2007, including MEDLINE, EMBASE, CINAHL,
      AMED, Cochrane and ZETOC, were searched systematically. We identified 475
      published papers relating to blood pressure, oxygen saturation and positioning,
      blood glucose and body temperature. REVIEW METHODS: Titles and abstracts were
      reviewed independently by two reviewers and 61 relevant studies were read in
      full. The quality of included studies was assessed and proformas were used to
      record detailed data. A narrative synthesis described how the evidence from the
      papers could inform our understanding of physiological parameters and their
      association with outcome. RESULTS: Current evidence suggests that patient outcome
      is worse when physiological parameters deviate from 'normal' in the acute phase
      of stroke. CONCLUSIONS: The evidence supports the need for monitoring and
      recording of blood pressure, oxygen saturation (including consideration of
      positioning), blood glucose and body temperature in the acute phase of stroke.
      This review has reinforced the importance of monitoring physiological parameters
      in the acute phase of stroke and adds support to the recommendation that
      monitoring should play a key role within nursing care.

PMID- 18039247
TI  - Understanding dementia amongst people in minority ethnic and cultural groups.
AB  - AIM: This paper is a report of a study to explore perceptions of ageing, dementia
      and ageing-associated mental health difficulties amongst British people of
      Punjabi Indian origin. BACKGROUND: People from ethnic minorities are often under
      represented in mental health services. Contributing factors may include lack of
      knowledge of dementia in these communities, lack of detection in primary care,
      expectations of family care and lack of appropriate services. For this to change,
      greater knowledge is needed about awareness and conceptualization of dementia in
      minority ethnic communities. METHOD: A focus-group study was conducted between
      2001 and 2003 with 49 English-, Hindi- and Punjabi-speaking British South Asians,
      aged 17-61 years. Views of ageing and ageing-associated difficulties were
      explored in initial groups. In a second set of groups, vignettes were used for
      more specific exploration of awareness and understanding of dementia. Data were
      subjected to thematic analysis. FINDINGS: Ageing was seen as a time of withdrawal
      and isolation, and problems as physical or emotional; cognitive impairment was
      seldom mentioned. There was an implication that symptoms of dementia partly
      resulted from lack of effort by the person themselves and possibly from lack of
      family care. Therefore people should overcome their own problems and family
      action might be part of the solution. There was a sense of stigma and a lack of
      knowledge about mental illness and services, alongside disillusionment with
      doctors and exclusion from services. CONCLUSION: Health promotion and health
      interventions delivered with respect for the cultural context are needed, as well
      as education of healthcare professionals about South Asian conceptualizations of
      dementia.

PMID- 18039248
TI  - Staffing adequacy, supervisory support and quality of care in long-term care
      settings: staff perceptions.
AB  - AIM: This paper is a report of a study to explore relationships between perceived
      care quality, self-assessed professional skills, and the perceptions of the
      quality-related factors. BACKGROUND: The work in long-term care is more demanding
      than in the past. The quality of care is strongly related to the well-being and
      job satisfaction of staff. Those emerge in part through a perception of resources
      allocated to caring and also through a perception of the quality achieved.
      METHOD: Data were collected in Finland in 2002 using a questionnaire sent to the
      nursing staff working in 112 wards in 40 long-term care institutions monitoring
      their care with the Resident Assessment Instrument System. Institutions were
      invited to participate the survey. The response rate was 70.2% (n = 1262). The
      respondents represented 3.8% of nursing personnel working in long-term care
      institutions. FINDINGS: Staff members who perceived staffing levels as inadequate
      and supervisory support as insufficient had lower perceptions of their own
      professional skills and the quality of care. Perceptions of empowering support
      behaviour were more strongly associated to self-assessed skills and to perceived
      care quality than perceptions of skills-oriented support activities. Staff
      members with short professional training, older staff members and staff members
      with long work experience in the unit had lower perceptions of their professional
      skills than other groups. CONCLUSION: The perception of adequate staffing and of
      sufficient supervisory support, especially empowering support increases the
      probability of perceiving the care quality as good. If supervisors concern
      themselves with staff members' perceptions, they can better identify the staffing
      needs and also the support needs of personnel.

PMID- 18039249
TI  - Adjustment to colostomy: stoma acceptance, stoma care self-efficacy and
      interpersonal relationships.
AB  - AIM: This paper is a report of a study to examine adjustment and its relationship
      with stoma acceptance and social interaction, and the link between stoma care
      self-efficacy and adjustment in the presence of acceptance and social
      interactions. BACKGROUND: There have been significant advances in stoma
      appliances and an increase in nurses specialising in stoma care. Despite this, a
      large proportion of patients continue to experience adjustment problems, which
      suggests that improvements in the management of the stoma are by themselves not
      enough to enhance psychosocial functioning. Illness acceptance and interpersonal
      relationships are widely reported as correlates of adjustment to chronic illness,
      but these have not been specifically examined in patients with a colostomy.
      Evidence of their association could offer stoma therapists alternative ways of
      aiding adjustment. METHOD: Between 2000 and 2002, 51 patients with colostomies
      provided demographic and clinical data and completed validated questionnaires to
      measure acceptance of the stoma, relationship with others and stoma care self
      efficacy 6 months after surgery. FINDINGS: Multiple regression analysis showed
      that stoma care self-efficacy, stoma acceptance, interpersonal relationship and
      location of the stoma were strongly associated with adjustment. The model
      explained 77% of the variance. Stoma-care self-efficacy accounted for 57.5%, the
      psychosocial variables 13% and location of the stoma 4.6%. The addition of
      gender, which was not statistically significant (P > 0.05), explained a further
      1.9% of the variance. CONCLUSION: Addressing psychosocial concerns should become
      part of the care routinely given to stoma patients. We recommend more emphasis on
      dispelling negative thoughts and encouraging social interactions.

PMID- 18039250
TI  - The construction of men who are nurses as gay.
AB  - AIM: This paper is a report of a study to examine the construction of the
      stereotype of male nurses as gay, and to describe how this discourse impacts on a
      group of New Zealand male nurses. BACKGROUND: A discourse stereotyping male
      nurses as gay is accompanied by one which privileges hegemonic masculinity and
      marginalizes homosexuality. METHOD: This social constructionist study drew on
      data collected from existing texts on men, nursing and masculinity and interviews
      with 18 New Zealand men conducted in 2003-2004. Discourse analysis, informed by
      masculinity theory and queer theory, was used to analyse the data. FINDINGS:
      Despite the participants' beliefs that the majority of male nurses are
      heterosexual, the stereotype persists. A paradox emerged between the 'homosexual'
      general nurse and the 'heterosexual' psychiatric nurse. The stigma associated
      with homosexuality exposes male nurses to homophobia in the workplace. The
      heterosexual men employed strategies to avoid the presumption of homosexuality;
      these included: avoiding contact with gay colleagues and overt expression of
      their heterosexuality. CONCLUSION: There is a paradox between widespread calls
      for men to participate more in caring and discourses which stereotype male nurses
      as gay and conflate homosexuality and sexual predation. These stigmatizing
      discourses create a barrier to caring and, aligned with the presence of
      homophobia in the workplace, deter men's entry into the profession and may be
      important issues with respect to their retention. Nurse educators must ensure
      that nurses are able to resist collusion with stigmatizing discourses that
      marginalize men (and women) in the profession through the perpetration of gender
      and sexual stereotypes.

PMID- 18039251
TI  - Holding together: caring for clients undergoing assisted reproductive
      technologies.
AB  - AIM: This paper is a report of a study to investigate the roles and experiences
      of nurses caring for clients undergoing assisted reproductive technologies.
      BACKGROUND: Little has been written on nurses' experiences of assisted
      reproductive technologies. Such interventions are emotionally fraught for
      clients, and working in areas of high emotional intensity can also be emotionally
      difficult for staff. Nurses are in a potentially unique position in the assisted
      reproductive technology environment in that, unlike other professionals who move
      in and out during the treatment cycle, they maintain a more constant contact with
      the client. METHOD: A qualitative approach was taken and a convenience sample of
      15 nurses from New Zealand was interviewed in 2005. Data were analysed using
      interpretive description. FINDINGS: The overarching theme identified was that of
      the potential role of the nurse to 'hold together' multiple components of the
      assisted reproductive technology process: holding together clients' emotional and
      physical experiences of assisted reproductive technologies; holding together the
      roles of different specialist team members; and holding together personal own
      emotions. It encompasses practices such as information-giving, interpreting,
      supporting and advocating. CONCLUSION: Assisted reproductive technologies nurses
      require recognition of their role and how it may positively contribute to
      clients' experiences, as well as adequate preparation and ongoing support. Nurses
      need to be educated in both the emotional and medical aspects involved in caring
      for clients being treated with these technologies.

PMID- 18039252
TI  - Characteristics of patient and healthcare service utilization associated with
      inappropriate hospitalization days.
AB  - AIM: This paper is a report of a study to examine the number of inappropriate
      days of hospitalization and to identify the characteristics of patient and
      healthcare service utilization associated with inappropriate hospital stays.
      BACKGROUND: Inappropriate hospitalization stays are recognized as an important
      indication of the misuse of healthcare services, but the published literature
      shows inconsistent findings on factors influencing this. METHOD: A descriptive,
      correlational study was carried out in September 2005, with a patient survey and
      a review of patient records. Data were collected for 383 patients discharged from
      eight general nursing care units in a tertiary teaching hospital in Korea.
      Inappropriate hospitalization days were defined as inpatient days not requiring
      continuous and active medical, nursing or paramedical treatment provided by
      hospital services, and were judged using the Korean version of the Appropriate
      Evaluation Protocol. Univariate and multiple regression analyses were performed
      to determine factors associated with inappropriate hospitalization days.
      FINDINGS: A total of 3076 hospitalization days were reviewed. The average
      proportion that were inappropriate was 5.1% (+/-16.0) per patient, and 14.1% of
      patients were determined to have had at least one inappropriate hospitalization
      day. The most common reason judged as appropriate was need for nursing/life
      support services. Statistically significant factors associated with inappropriate
      stay included gender, age, primary disease, length of stay and ward bed occupancy
      level during the patient's hospitalization. CONCLUSION: Managers should take into
      account patient and clinical characteristics to promote better utilization of
      hospital resources.

PMID- 18039253
TI  - Emotional toil: psychosocial care in rural settings for patients with cancer.
AB  - AIM: This paper is a report of a study to identify experienced rural nurses'
      perceptions of key issues related to the provision of effective psychosocial care
      for people with cancer in rural settings. BACKGROUND: A cancer diagnosis has a
      major impact on psychological and emotional wellbeing, and psychosocial support
      provided by nurses is an integral part of ensuring that people with cancer have
      positive outcomes. Although, ideally, people with cancer should be managed in
      specialist settings, significant numbers are cared for in rural areas. METHODS:
      Using a qualitative descriptive approach, three focus groups were conducted in
      2005 with 19 nurses in three hospitals in rural Victoria, Australia. FINDINGS:
      Participants indicated that a key issue in providing psychosocial care to
      patients with cancer in the rural setting was their own 'emotional toil'. This
      Global Theme encapsulated three Organizing Themes- task vs. care, dual
      relationships and supportive networks--reflective of the unique nature of the
      rural environment. Nurses in rural Australia are multi-skilled generalists and
      they provide care to patients with cancer without necessarily having specialist
      knowledge or skill. The fatigue and emotional exhaustion that the nurses
      described often has a major impact on their own well-being. CONCLUSION: In the
      rural context, it is proposed that clinical supervision may be an important
      strategy to support clinicians who face emotional exhaustion as part of their
      cancer nursing role.

PMID- 18039254
TI  - Nurse absenteeism and workload: negative effect on restraint use, incident
      reports and mortality.
AB  - AIM: This paper is a report of a study to assess the impact of nurse absenteeism
      on the quality of patient care. BACKGROUND: Nurse absenteeism is a growing
      management concern. It can contribute to understaffed units, staffing
      instability, and other factors that could have a negative impact on patient care.
      The impacts of absenteeism on the quality of nursing care have rarely been
      studied. METHOD: Retrospective monthly data from incident reports and staffing
      records in six inpatient units for 2004 were analysed. Dependent variables were
      the numbers of restraints, alternatives to restraints, incident reports, deaths,
      and length of stay. Explanatory variables were nurse absenteeism hours, patient
      days per nursing staff, and interaction between these variables. Controls were
      patient acuity and unit characteristics. Fixed effects regressions were analysed
      as regular or negative binomial models. FINDINGS: Neither high Registered Nurse
      absenteeism nor high patient load was related to restraint use when taken
      separately. However, high Registered Nurse absenteeism was related to restraint
      use when patient load was high. Registered Nurse absenteeism was related to a
      lower use of alternatives to restraints. Incident reports were increased by high
      patient load, but not absenteeism, or absenteeism given patient load. When both
      patient load and absenteeism were high, deaths were higher also. CONCLUSION:
      Absenteeism alone may not be a strong factor in lowering quality, but the
      combination of high Registered Nurse absenteeism and high patient load could be a
      factor. Staffing and absenteeism may be part of a vicious cycle in which low
      staffing contributes to unit absenteeism, which contributes to low staffing, and
      so on.

PMID- 18039255
TI  - EPUAP classification system for pressure ulcers: European reliability study.
AB  - AIM: This paper is a report of a study of the inter-observer reliability of the
      European Pressure Ulcer Advisory Panel pressure ulcer classification system and
      of the differential diagnosis between moisture lesions and pressure ulcers.
      BACKGROUND: Pressure ulcer classification is a valuable tool to provide a common
      description of ulcer severity for the purposes of clinical practice, audit and
      research. Despite everyday use of the European Pressure Ulcer Advisory Panel
      system, its reliability has been evaluated in only a limited number of studies.
      METHODS: A survey was carried out between September 2005 and February 2006 with a
      convenience sample of 1452 nurses from five European countries. Respondents
      classified 20 validated photographs as normal skin, blanchable erythema, pressure
      ulcers (four grades), moisture lesion or combined lesion. The nurses were
      familiar with the use of the European Pressure Ulcer Advisory Panel
      classification scale. RESULTS: Pressure ulcers were often classified erroneously
      (kappa = 0.33) and only a minority of nurses reached a substantial level of
      agreement. Grade 3 lesions were regularly classified as grade 2. Non-blanchable
      erythema was frequently assessed incorrectly as blanchable erythema. Furthermore,
      the differential diagnosis between moisture lesions and pressure ulcers appeared
      to be complicated. CONCLUSION: Inter-observer reliability of the European
      Pressure Ulcer Advisory Panel classification system was low. Evaluation thus
      needs to focus on both the clarity and complexity of the system. Definitions and
      unambiguous descriptions of pressure ulcer grades and the distinction between
      moisture lesions will probably enhance clarity. To simplify the current
      classification system, a reduction in the number of grades is suggested.

PMID- 18039256
TI  - Nursing's ways of knowing and dual process theories of cognition.
AB  - AIM: This paper is a comparison of nursing's patterns of knowing with the systems
      identified by cognitive science, and evaluates claims about the equal-status
      relation between scientific and non-scientific knowledge. BACKGROUND: Ever since
      Carper's seminal paper in 1978, it has been taken for granted in the nursing
      literature that there are ways of knowing, or patterns of knowing, that are not
      scientific. This idea has recently been used to argue that the concept of
      evidence, typically associated with evidence-based practice, is inappropriately
      restricted because it is identified exclusively with scientific research. METHOD:
      The paper reviews literature in psychology which appears to draw a comparable
      distinction between rule-based, analytical cognitive processes and other forms of
      cognitive processing which are unconscious, holistic and intuitive. FINDINGS:
      There is a convincing parallel between the 'patterns of knowing' distinction in
      nursing and the 'cognitive processing' distinction in psychology. However, there
      is an important difference in the way the relation between different forms of
      knowing (or cognitive processing) is depicted. In nursing, it is argued that the
      different patterns of knowing have equal status and weight. In cognitive science,
      it is suggested that the rule-based, analytical form of cognition has a
      supervisory and corrective function with respect to the other forms. CONCLUSIONS:
      Scientific reasoning and evidence-based knowledge have epistemological priority
      over the other forms of nursing knowledge. The implications of this claim for
      healthcare practice are briefly indicated.

PMID- 18039257
TI  - In response to: Fu M.R., McDaniel R.W. & Rhodes V.A. (2007) Measuring symptom
      occurrence and symptom distress: development of the Symptom Distress Index.
      Journal of Advanced Nursing 59, 623-634.

PMID- 18039258
TI  - In response to: Bradbury-Jones C., Sambrook S. & Irvine F. (2007) The meaning of
      empowerment for nursing students: a critical incident study. Journal of Advanced
      Nursing 59(4), 342-351.

PMID- 18039271
TI  - Flow visualization through two types of aortic prosthetic heart valves using
      stereoscopic high-speed particle image velocimetry.
AB  - The number of candidates waiting for a heart valve replacement rises yearly. Even
      though there is a trend toward implantation of biological valves or
      reconstruction, the prosthetic heart valves (PHVs) are still commonly used for
      implantation or as a part of cardiac assist devices in many countries worldwide.
      However, the hemodynamic consequences of these valves are still not completely
      understood. Unfortunately, these devices currently do not perform sufficiently on
      a long-term basis and may lead to several complications, many of them are related
      to fluid mechanical aspects. A novel method, stereoscopic high-speed particle
      image velocimetry, was applied to quantify all three velocity components behind a
      PHV in detailed time domain. In this study, we compared clinically used bileaflet
      aortic prosthetic (ATS) valve and monoleaflet prototype of tilting disk PHV. The
      absolute velocities calculated out of two and three velocity components were
      compared to each other to estimate the overall difference in the desired region
      of interest. The most significant discrepancies between the two- and three
      component absolute velocities were found at the regions of Valsalva sinuses and
      in a major jet stream of monoleaflet PHV.

PMID- 18039272
TI  - Hemodialysis machine air detectors need not detect microbubbles.

PMID- 18039275
TI  - Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute
      lung injury.
AB  - Recent studies on endotoxin/lipopolysaccharide (LPS)-induced acute inflammatory
      response in the lung are reviewed. The acute airway inflammatory response to
      inhaled endotoxin is mediated through Toll-like receptor 4 (TLR4) and CD14
      signalling as mice deficient for TLR4 or CD14 are unresponsive to endotoxin.
      Acute bronchoconstriction, tumour necrosis factor (TNF), interleukin (IL)-12 and
      keratinocyte-derived chemokine (KC) production, protein leak and neutrophil
      recruitment in the lung are abrogated in mice deficient for the adaptor molecules
      myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)
      domain-containing adaptor protein (TIRAP), but independent of TIR-domain
      containing adaptor-inducing interferon-beta (TRIF). In particular, LPS-induced
      TNF is required for bronchoconstriction, but dispensable for inflammatory cell
      recruitment. Lipopolysaccharide induces activation of the p38 mitogen-activated
      protein kinase (MAPK). Inhibition of pulmonary MAPK activity abrogates LPS
      induced TNF production, bronchoconstriction, neutrophil recruitment into the
      lungs and broncho-alveolar space. In conclusion, TLR4-mediated,
      bronchoconstriction and acute inflammatory lung pathology to inhaled endotoxin
      are dependent on TLR4/CD14/MD2 expression using the adapter proteins TIRAP and
      MyD88, while TRIF, IL-1R1 or IL-18R signalling pathways are dispensable. Further
      downstream in this axis of signalling, TNF blockade reduces only acute
      bronchoconstriction, while MAPK inhibition abrogates completely endotoxin-induced
      inflammation.

PMID- 18039276
TI  - Prenatal administration of vitamin A alters pulmonary and plasma levels of
      vascular endothelial growth factor in the developing mouse.
AB  - Vitamin A and the retinoids play a unique role in mammalian embryonic and foetal
      development and are essential for both cellular differentiation and the
      establishment of normal morphogenesis. Vascular endothelial growth factor (VEGF)
      is a known potent mitogenic factor that plays a key role in lung development and
      function maintenance. In order to contribute to a better knowledge of the
      modulating effects of vitamin A in lung development, we investigated the effects
      of the antenatal administration of vitamin A on VEGF expression in lungs and
      plasma from foetuses and neonates. Pregnant mice were subjected to subcutaneous
      administration of vitamin A on the 12th gestational day. The lungs and plasma
      from foetuses and neonates were collected daily from the 15th gestational day
      till the day of birth. Our results show that vitamin A modulates VEGF
      concentrations both in lungs and plasma. Statistically significant differences
      were observed at gestational days 15 (P = 0.004 for lungs; P < 0.0001 for
      plasma), 16 (P < 0.0001 for lungs and plasma) and 18 (P < 0.0001 for lungs; P <
      0.05 for plasma). Vitamin A tends to increase the expression of this factor in
      the lung, particularly during the critical period of perinatal adaptation to
      postnatal life. These effects seem to be spatial and temporally regulated, and
      point out to the important role of vitamin A during lung development.

PMID- 18039277
TI  - Pathology and virus dispersion in cynomolgus monkeys experimentally infected with
      severe acute respiratory syndrome coronavirus via different inoculation routes.
AB  - Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes SARS.
      The pathogenic mechanisms of SARS-CoV remain poorly understood. Six cynomolgus
      monkeys were inoculated with the HKU39849 isolate of SARS-CoV via four routes.
      After intranasal inoculation, the virus was isolated from respiratory swabs on
      days 2-7 postinoculation (p.i.) and virus genome was detected in intestinal
      tissues on day 7 p.i. Virus was not detected after intragastric inoculation.
      After intravenous inoculation, infectious virus was isolated from rectal swabs,
      and virus antigen was detected in intestinal cells on day 14 p.i. After
      intratracheal (i.t.) inoculation, virus antigen-positive alveolar cells and
      macrophages were found in lung and infectious virus was detected in lymphoid and
      intestinal tissues. The peribronchial lymph nodes showed evidence of an immune
      response. Lung tissue and/or fluid and/or the peribronchial lymph node of the
      intratracheally inoculated animals had high TNF-alpha, IL-8 and IL-12 levels.
      SARS lung lesions are only generated in monkeys by i.t. inoculation. The virus
      appears to spread into and perhaps via the intestinal and lymphatic systems. It
      has been suggested previously that viraemia may cause intestinal infections in
      SARS patients.

PMID- 18039278
TI  - Laser capture microdissection reveals dose-response of gene expression in situ
      consequent to asbestos exposure.
AB  - The genes that mediate fibroproliferative lung disease remain to be defined.
      Prior studies from our laboratory showed by in situ hybridization and
      immunohistochemistry that the genes coding for tumour necrosis factor alpha,
      transforming growth factor beta, the platelet-derived growth factor A and B
      isoforms, and alpha-1 pro-collagen are expressed in fibroproliferative lesions
      that develop quickly after asbestos inhalation. These five genes, along with
      matrix metalloproteinase 9, a collagenase found to be increased in several lung
      diseases, are known to control matrix production and cell proliferation in humans
      and animals. Here we show by laser capture microdissection that (i) The six genes
      are expressed at significantly higher levels in the asbestos-exposed mice when
      comparing the same anatomic regions 'captured' in unexposed mice. (ii) The
      bronchiolar-alveolar duct (BAD) junctions, where the greatest number of fibres
      initially deposit, were always significantly higher than the other anatomic
      regions for each gene. The first alveolar duct bifurcation (ADB) generally was
      higher than the second ADB, the ADBs were always significantly higher than the
      airway walls and pleura, and the airway walls and pleura were generally higher
      than the unexposed tissues. (iii) Animals exposed for 3 days always exhibited
      significantly higher levels of gene expression at the BAD junctions and ADBs than
      animals exposed for 2 days. To our knowledge, this is the first demonstration of
      a dose-response to a toxic particle in situ, and this response appears to be
      dependent on the number of fibres that deposits at the individual anatomic site.

PMID- 18039279
TI  - Lysosomal acid lipase over-expression disrupts lamellar body genesis and alveolar
      structure in the lung.
AB  - The functional role of neutral lipids in the lung is poorly understood. Lysosomal
      acid lipase (LAL) is a critical enzyme in hydrolysis of cholesteryl esters and
      triglycerides to generate free fatty acids and cholesterol in lysosomes. Human
      LAL was over-expressed in a doxycycline-controlled system in mouse respiratory
      epithelial cells to accelerate intracellular neutral lipid degradation and
      perturb the surfactant homeostasis in the lung. In this animal system, neutral
      lipid concentrations of pulmonary surfactant were reduced in bronchoalveolar
      lavage fluid (BALF) in association with decrease of surfactant protein C (SP-C)
      gene expression. The size and the number of lamellar bodies in alveolar type II
      epithelial cells (AT II cells) were significantly reduced accordingly. The number
      of macrophages required for surfactant recycling in BALF was also significantly
      reduced. As a result of these combinatory effects, emphysema of the alveolar
      structure was observed. Taken together, neutral lipid homeostasis is essential
      for maintenance of lamellar body genesis and the alveolar structure in the lung.

PMID- 18039280
TI  - Matrix metalloproteinase-2, -9 and -13 are involved in fibronectin degradation of
      rat lung granulomatous fibrosis caused by Angiostrongylus cantonensis.
AB  - Pulmonary granuloma formation and fibrosis were experimentally induced in Sprague
      Dawley strain rats by Angiostrongylus cantonensis. Increased protein levels of
      matrix metalloproteinase (MMP)-2, -9, -13 and the imbalance between these enzymes
      and metalloproteinase inhibitors, tissue inhibitors of MMPs (TIMP-1 and -2),
      occur during granulomatous fibrosis. Activation of proteolytic enzymes (MMP-2, -9
      and -13) and fibronectin degradation occur simultaneously. Furthermore, the
      present study demonstrated that fibronectin avidly binds MMP-2, -9 or -13.
      Immunohistochemical observations also showed the localization of MMP-13, TIMP-1
      and -2 within the infiltrating leucocytes. These results suggest that MMP-2, -9
      and -13 may participate in the fibronectin degradation of A. cantonensis-induced
      granulomatous fibrosis.

PMID- 18039281
TI  - What do measures of 'oral health-related quality of life' measure?
AB  - The terms 'health-related quality of life' and 'quality of life' are now in
      common use to describe the outcomes of oral health conditions and therapy for
      those conditions. In addition, there has been a proliferation of measures
      designed to quantify those outcomes. These measures, which were initially
      designated as socio-dental indicators or subjective oral health indicators are
      now more usually referred to as measures of oral health-related quality of life
      (OH-QoL). This is based on the assumption that the functional and psychosocial
      impacts they document must, of necessity, affect the quality of life. While this
      assumption has been subject to critical scrutiny in medicine, this is not the
      case with dentistry. Consequently, exactly what is being measured by indexes of
      OH-QoL is somewhat unclear. Based on the debate between Gill and Feinstein and
      Guyatt and Cook, we outline a number of criteria by means of which the construct
      addressed by measures of OH-QoL may be assessed. These are concerned with how the
      measures were developed and validated. These criteria are then used to appraise
      five of the many measures that have been developed over the past 20 years--the
      GOHAI, OHIP, OIDP, COHQoL and OH-QoL. The main conclusion is that while all
      document the frequency of the functional and psychosocial impacts that emanate
      from oral disorders they do not unequivocally establish the meaning and
      significance of those impacts. Consequently, the claim that oral disorders affect
      the quality of life has yet to be clearly demonstrated. Verifying this claim
      requires further qualitative studies of the outcomes of oral disorders as
      perceived by patients and persons, and the concurrent use of measures that more
      explicitly address the issue of quality of life.

PMID- 18039282
TI  - Statistical issues on the analysis of change in follow-up studies in dental
      research.
AB  - OBJECTIVE: To provide an overview to the problems in study design and associated
      analyses of follow-up studies in dental research, particularly addressing three
      issues: treatment-baselineinteractions; statistical power; and nonrandomization.
      BACKGROUND: Our previous work has shown that many studies purport an interacion
      between change (from baseline) and baseline values, which is often based on
      inappropriate statistical analyses. A priori power calculations are essential for
      randomized controlled trials (RCTs), but in the pre-test/post-test RCT design it
      is not well known to dental researchers that the choice of statistical method
      affects power, and that power is affected by treatment-baseline interactions. A
      common (good) practice in the analysis of RCT data is to adjust for baseline
      outcome values using ancova, thereby increasing statistical power. However, an
      important requirement for ancova is there to be no interaction between the groups
      and baseline outcome (i.e. effective randomization); the patient-selection
      process should not cause differences in mean baseline values across groups. This
      assumption is often violated for nonrandomized (observational) studies and the
      use of ancova is thus problematic, potentially giving biased estimates, invoking
      Lord's paradox and leading to difficulties in the interpretation of results.
      METHODS: Baseline interaction issues can be overcome by use of statistical
      methods; not widely practiced in dental research: Oldham's method and multilevel
      modelling; the latter is preferred for its greater flexibility to deal with more
      than one follow-up occasion as well as additional covariates To illustrate these
      three key issues, hypothetical examples are considered from the fields of
      periodontology, orthodontics, and oral implantology. CONCLUSION: Caution needs to
      be exercised when considering the design and analysis of follow-up studies.
      ancova is generally inappropriate for nonrandomized studies and causal inferences
      from observational data should be avoided.

PMID- 18039283
TI  - Gender differences in reported dental fear and fear of dental pain.
AB  - OBJECTIVES: Gender differences in dental fear have been of increasing interest
      among clinicians and researchers. The objectives of this study were to assess:
      (i) gender differences in reports of global dental fear, global fear of dental
      pain, and specific fear of dental pain; (ii) how the wording of questions about
      specific fear of dental pain influences a subjective report, and (iii) the
      interactions between gender differences and wording effects in the reports of
      specific fear of dental pain. METHODS: A telephonic survey of 504 adult
      Floridians was conducted in 2004. Data collected included six measures of
      specific fear of dental pain, one measure of global fear of dental pain, one
      measure of global dental fear, and demographic information. RESULTS: Women were
      more likely to report global dental fear, global fear of dental pain, and
      specific fear of dental pain than men, and both women and men were more likely to
      report 'dread' of dental pain than 'fear' of dental pain. CONCLUSIONS: Our
      findings suggest that: (i) there are gender differences in reports of dental fear
      and fear of dental pain; and (ii) both men and women are more willing to express
      their fearful feelings regarding dentistry using a more socially acceptable term.

PMID- 18039284
TI  - Cultural factors and children's oral health care: a qualitative study of carers
      of young children.
AB  - OBJECTIVE: This qualitative study sought to identify cultural beliefs, practices
      and experiences that influence access to preventive oral health care for young
      children from different racial and ethnic groups. METHODS: Four to six focus
      groups in each of the African-American, Chinese, Latino and Filipino communities
      in San Francisco, California were included in the study. Participants were carers
      of children aged 1-5 years. The 22 groups (n = 177 participants) were stratified
      by carer's age and, except in the African-American community, by whether US or
      non-US born. Sessions were conducted in different languages as needed. RESULTS:
      Lack of knowledge and beliefs about primary teeth created barriers to early
      preventive care in all groups. In Chinese groups more than others, health beliefs
      regarding disease causation and prevention influenced access to preventive dental
      care. In all groups, multiple family carers, especially elders, influenced access
      to preventive care. Dental fear, whether derived from prevailing community
      beliefs or personal negative dental experiences, greatly influenced attitudes
      regarding accessing preventive care. CONCLUSION: There are both similarities and
      differences between racial/ethnic groups in how cultural beliefs and experiences
      influence young children's access to dental care and how it might be improved.

PMID- 18039285
TI  - Psychosocial factors and early childhood caries among low-income African-American
      children in Detroit.
AB  - OBJECTIVES: This study sought to advance knowledge of the social determinants of
      oral health, by examining how several specific maternal health beliefs,
      behaviors, and psychosocial factors relate to young children's early childhood
      caries (ECC) status in a lower-income African-American population. METHODS: Data
      were collected by the Detroit Dental Health Project (NIDCR grant), a population
      based study of 1021 African-American families with at least one child under 6
      years of age and living in 39 low-income Census tracts in Detroit, Michigan.
      Analyses were limited to 719 children aged 1-5 years and their biological
      mothers, and conducted in SUDAAN to account for the complex sampling design.
      Survey data included health belief scales on mothers' self-efficacy, feelings of
      fatalism, knowledge about appropriate bottle use and children's oral hygiene
      needs, brushing habits, psychosocial measures of depressive symptoms (CES-D),
      parenting stress, and availability of instrumental social support. The child's
      age, dental insurance status, dental visit history, and 1-week brushing frequency
      were also included in the model. Children's ECC status, based on a dental
      examination, was the main outcome. The dental team used the International Caries
      Detection and Assessment System (ICDAS) criteria for caries detection. Each child
      was classified as either caries-free or having ECC or severe ECC (S-ECC) based on
      the case definition of ECC proposed by an expert panel for research purposes with
      preschool-aged children. RESULTS: The dental team followed a specific examination
      protocol and established reliable and consistent ratings of ECC based on the
      ICDAS criteria. The inter-rater reliability kappa was 0.83 overall, and the intra
      rater reliability kappa was 0.74 overall. One-third of the children had ECC, and
      20% had severe ECC. Age of the child and lower parenting stress scores were each
      positively associated with ECC, while higher education and income were
      protective. Maternal oral health fatalism and knowledge of children's hygiene
      needs were associated with ECC among preschool-aged children. ECC was higher
      among younger children who had past restorative care. CONCLUSIONS: These findings
      call attention to the high prevalence of ECC in this population and the need to
      consider psychosocial as well as traditional risk factors in developing
      interventions to reduce oral health disparities.

PMID- 18039286
TI  - Dental caries and childhood obesity: roles of diet and socioeconomic status.
AB  - OBJECTIVE: Our objective was to determine (a) if caries and obesity were
      associated in a pediatric population and (b) if so, then to explore diet and
      socioeconomic status as additional risk factors. METHODS: Subjects were recruited
      at birth and are members of the Iowa Fluoride Study. Data such as parental age,
      parental education levels and family incomes were obtained by questionnaire at
      recruitment. Children's primary dentition was examined and their weight and
      height measured at 4.5-6.9 years of age. Parental weight and height were measured
      when children were 7.6-10.9 years of age. Beverage and nutrient intake patterns
      were obtained from 3-day food and beverage diaries completed at 1, 2, 3, 4 and 5
      years of age. RESULTS: Children with caries had lower family incomes, less
      educated parents, heavier mothers and higher soda-pop intakes at 2, 3 and for 1-5
      years than children without caries (P < 0.05). 'Overweight' children had less
      educated fathers and heavier parents than 'normal' weight children (P < 0.05).
      Children 'at risk' of overweight had higher caries rates than 'normal' or
      'overweight' children (P < 0.05). In stepwise logistic regression models to
      predict caries experience, soda-pop intakes were displaced by mother's education,
      leaving 'at risk' of overweight and mother's education in the final model.
      CONCLUSION: Caries and obesity coexist in children of low socioeconomic status.
      Public health measures to improve dietary education and access to appropriate
      foodstuffs could decrease the risk of both diseases.

PMID- 18039287
TI  - Influences of market competition on dental care utilization under the global
      budget payment system.
AB  - OBJECTIVES: The degrees of market competition usually influence providers'
      behaviors. This study investigated the influence of medical market competition on
      the utilization of dental care under the global budget payment system. This study
      also examined the relative factors that influence the utilization of dental care.
      METHODS: This study used the healthcare sub-regions (HCSRs) in the healthcare net
      as the observation units. The dataset was the National Health Insurance dental
      care claim data from 1999 to 2002. The degree of market competition of dental
      care was measured by the Herfindahl Index (HI). The influences of medical market
      competition on the utilization of dental care were analyzed by multiple linear
      regression analysis. RESULTS: When the market had a higher degree of competition,
      people had a higher number of dental utilizations after controlling for the other
      variables. When market competition increased by 1%, annual expenditures and
      frequencies of dental care as well as frequencies of tooth-filling per person
      increased by 0.4%. Thirty-three percent of dental expenditures could be explained
      by increases in the degree of market competition. Females or highly educated
      people had a positive correlation with dental utilization. However, the
      agricultural population negatively correlated with dental utilization. Average
      household income had no significant relationship with the frequency of dental
      care but had a significant negative association with dental expenditures when
      dental care was covered by health insurance. CONCLUSIONS: After the global budget
      payment system for dental care was implemented, increases in dental care market
      competition led to the increase in utilization of dental care services.

PMID- 18039288
TI  - Osteoporosis and the general dental practitioner: reliability of some digital
      dental radiological measures.
AB  - OBJECTIVES: Dental radiographs are relatively inexpensive and are regularly made
      of a large fraction of the adult population; therefore, they represent an
      enormous potential as a screening tool for osteoporosis. Monitoring the
      population by means of dual X-ray absorptiometry (DXA), which is currently the
      most accepted method for diagnosing osteoporosis, involves enormous costs and
      facilities. In previous studies, it was shown that the radiographic trabecular
      pattern shows correlations with the bone mineral density (BMD) as measured by
      DXA. The objective of this study was to assess the reproducibility of the
      quantitative analysis of the trabecular pattern on dental radiographs. METHODS:
      Six regions of interest were selected manually on three digital radiographic
      images of 20 women. This process was performed 10 times resulting in 1200 image
      samples. For each image sample 26 parameters were measured. The reliability of
      the parameters was evaluated by means of Cronbach's alpha. RESULTS: Of the values
      of Cronbach's alpha 83% is at least 0.9 and 99% is at least 0.8. CONCLUSIONS: The
      measurements of the parameters used in this study are very reproducible.
      Therefore, the manual selection of the regions of interest does not introduce
      large amounts of noise. The imaging parameters potentially offer an accurate tool
      for the prediction of BMD values.

PMID- 18039289
TI  - The concept of validity in sociodental indicators and oral health-related quality
      of-life measures.
AB  - BACKGROUND: Most of the psychometric instruments used to measure quality of life
      associated with oral impairment and disability from the perspectives of older
      adults focus on negative experiences, and pay little attention to the possibility
      of positive reactions to disablement. This oversight challenges the validity of
      the instruments in current use, and raises questions about the process used to
      validate them. OBJECTIVES: In this study, we consider the general attributes of
      psychometric validity, and how they have been applied to oral health-related
      instruments. CONCLUSIONS AND RECOMMENDATIONS: The psychometric characteristics
      and predictive validity of existing dental instruments are still weak, probably
      because the instruments fail to address the broad range of personal variables
      that influence oral health, disability and quality of life. We recommend,
      therefore, that a continuous process of validation be adopted to include: (1)
      assessments of the theoretical framework supporting the instruments; (2)
      evaluations of the focus and structure of the questions used; and (3)
      enhancements of the prediction value of instruments applicable to oral health
      related beliefs and behaviours.

PMID- 18039290
TI  - Fluoride intake and urinary excretion in 6- to 7-year-old children living in
      optimally, sub-optimally and non-fluoridated areas.
AB  - OBJECTIVES: This study was designed to measure total intake, urinary excretion
      and estimated retention of fluoride in children under customary fluoride intake
      conditions, living in either fluoridated or low-fluoride areas of north-east
      England. Subsidiary aims were to investigate the relationships between the
      variables measured. METHODS: Using a randomized cluster design with schools as
      the sampling units, four schools from a non-fluoridated area and two from a
      fluoridated area were selected from the schools chosen to participate in the
      study. Fluoride intake from diet and toothbrushing was assessed using a 3-day
      food diary and fluoride analysis of expectorated saliva during toothbrushing.
      Samples of all foods and drinks consumed were measured for fluoride content using
      direct and indirect silicon-facilitated diffusion methods as appropriate. Urinary
      fluoride excretion and urine volume were measured over 24 h and estimation of
      fractional urinary fluoride excretion (FUFE) and fluoride retention made from
      collected data. Following descriptive analysis of variables, Pearson's
      correlations investigated relationships between fluoride content of home tap
      water, daily fluoride intake, excretion and retention. RESULTS: Thirty-three
      children completed the study: 18 receiving non-fluoridated water [mean = 0.08 (+/
      0.03) mg F/l], nine sub-optimally fluoridated water [mean = 0.47 (+/-0.09) mg
      F/l] and six optimally fluoridated water [mean = 0.82 (+/-0.13) mg F/l] at the
      time of the study. Complete data on F intake, excretion and retention were
      available for 29 children. Mean fluoride intake from diet and toothpaste ranged
      from 0.031 (+/-0.025) mg/kg body weight (bw)/day for the low-fluoride area to
      0.038 (+/-0.038) and 0.047(+/-0.008) mg/kg bw/day for sub-optimally and optimally
      fluoridated areas respectively. Contribution of toothpaste to total fluoride
      intake ranged from 3% to 93% with mean values of 57%, 35% and 47% for children
      receiving low, sub-optimally and optimally fluoridated water respectively. FUFE
      ranged from a mean of 32% (+/-13%) for the optimally fluoridated area to 44% (+/
      33%) for the low-fluoride area. Fluoride retention was not correlated with the
      fluoride concentration of home water supply, but was strongly positively
      correlated (P < 0.001) with total daily fluoride intake. CONCLUSIONS: In an
      industrialized country, total fluoride intake, urinary excretion and consequently
      fluoride retention no longer reflect residence in a community with a non
      fluoridated or fluoridated water supply. Fluoride toothpaste contributes a
      significant proportion of total ingested fluoride in children, particularly in
      low-fluoride areas.

PMID- 18039291
TI  - Trends in the incidence, mortality, and survival rates of oral and pharyngeal
      cancer in a high-risk area in Michigan, USA.
AB  - OBJECTIVE: The aim of this analysis was to analyze the incidence, mortality and
      survival rates for the city of Detroit and Wayne County, Michigan. In Detroit,
      about four out of the five residents are African-Americans. METHODS: Rates and
      standard errors on oral cancer incidence, survival, and mortality by county of
      residence, race, gender, stage of diagnosis were provided by the Michigan Cancer
      Surveillance Program, which is maintained by the Michigan Department of Community
      Health. Rates were expressed per 100,000 individuals and age adjusted to reflect
      the distribution of the USA population in 2000. Analysis for trends was conducted
      by the authors using the National Cancer Institutes' joinpoint regression program
      (version 3.0). RESULTS: In 1993-2002, the incidence rate of oral cancer in
      Michigan (one of the 50 states in the USA) was 11.3 per 100,000, and in the city
      of Detroit, it was 16.6. In African-American males in Michigan the incidence rate
      was 24.3 per 100,000, one of the highest among all American males. The city of
      Detroit, with 9% of the total state population, had 13.1% of all new cases.
      Between 1993 and 2002, there was a drop in incidence rates in Michigan and
      Detroit. However, there was an increase in mortality rates in Michigan and
      Detroit between 2000 and 2002. In Detroit, the incidence and mortality rates of
      'white' and African-American males were not different and the highest incidence
      rates were found in adults between the ages of 50 and 74 years. In the state, the
      peak incidence rates were found in adults 75 years or older. In 2000-2002,
      residents of Detroit had the lowest percentage (28.3%) of cases detected at early
      cancerous stage (in situ or localized) compared with rates in Michigan. African
      Americans in Michigan had a 5-year survival rate of 34.9% compared with the state
      average of 54.6%. CONCLUSIONS: African-American males in Detroit accounted for a
      larger proportion of the oral cancer cases relative to their population size.
      There was surprising similarity between the incidence and mortality rates of
      African and 'white' Americans in Detroit. While the incidence rates have declined
      in Michigan and Detroit, mortality rates have increased between 2000 and 2002.
      This finding is contrary to national trends. In order to target programs to
      prevent oral cancer, oral cancer statistics for in small areas or high-risk
      populations should be evaluated separately.

PMID- 18039294
TI  - How reliable is the current evidence looking at the efficacy of harm reduction
      and motivational interviewing interventions in the treatment of patients with a
      dual diagnosis?
AB  - Current policy from the Department of Health advocates for an integrated approach
      to treating patients with a dual diagnosis. However, pragmatic and clinically
      effective brief interventions that can be delivered by nurses across mental
      health settings remain underdeveloped. Motivational interviewing has had some
      successful exposure in the field of dual diagnosis; however, harm reduction
      remains unexplored both conceptually and in terms of clinical intervention. This
      literature review examines the notion of harm reduction as a method of
      identifying and reducing the harm associated with the misuse of drugs and alcohol
      in relation to mental health problems. Currently there is a paucity of good
      quality evidence for integrated interventions in the treatment of dually
      diagnosed patients. Therefore, the papers are analysed in respect of their
      methodological quality and contribution to the evidence base to inform both
      future research and mental health nursing practice.

PMID- 18039292
TI  - Caries risk factors in the permanent dentition of Tanzanian children: a cohort
      study (1997-2003).
AB  - OBJECTIVE: The aims of the cohort study were to study the association between
      permanent dentition caries and malnutrition and other risk factors or indicators
      in a group of children with little or no access to restorative and preventive
      dental care. METHODS: The study was conducted at two primary schools in Dar es
      Salaam, Tanzania in the period 1997-2003. One school recruits its children from
      affluent families and the other school is attended by the children of poor
      families. The children attended grade 1 at the first examination and had a mean
      age of 7.6 years (SD = 0.4); when the study was completed, the mean age was 13.3
      years. Two-hundred and eighteen children examined in 1997 were re-examined in
      1999; 147 of the children were examined in 1997 as well as in 2003, and 122
      children were examined in all three years. An age- and sex-based body mass index
      (BMI) was computed to determine the nutritional status of each child. Each year,
      the same standard methods were used to determine the count of lactobacilli and
      mutans streptococci, stimulated flow rate and buffering capacity of saliva, and
      caries. Risk ratios were computed with generalized linear models using the tooth
      as the unit of analysis. RESULTS: Mean annual caries increment was 0.27 in the
      period 1997-1999 and 0.80 in the period 1999-2003 with most children developing
      no caries at all. Malnutrition at baseline in 1997 was insignificantly predictive
      for the development of caries, whereas a low stimulated flow rate of saliva (< or
      =0.7 ml/min) and a high count of lactobacilli (> or =100,000/ml) at baseline in
      1997 were significantly associated. However, the generalized linear models for
      the two time periods 1997-1999 and 1999-2003 presented a confusing picture with
      different risk ratios and without consistency of the associations between the
      exposure variables and the development of caries. In accordance with this
      finding, the consistency of the exposure variables over time for the individuals
      was very low. CONCLUSIONS: The results were inconclusive and left us with more
      questions than answers. The findings do, however, support the view that our
      methods for predicting caries are inappropriate or nonexistent.

PMID- 18039295
TI  - Use of the HoNOSCA scale in the teamwork of inpatient child psychiatry unit.
AB  - The aims of this study were to introduce the Health of the Nation Outcome Scales
      for Children and Adolescents (HoNOSCA) into the clinical practice, to assess the
      possibilities to use HoNOSCA in the interdisciplinary teamwork of child
      psychiatric inpatient unit and to analyse differences in evaluation of HoNOSCA
      among team members scoring different diagnostic groups of children. HoNOSCA was
      translated into Lithuanian and team members were trained to use the scale. Inter
      rater reliabilities between various pairs of specialists and between all members
      of the team were calculated using intraclass correlations calculated for each
      item of the scale and total score. Scoring differences in children with
      externalized and internalized disorders between psychiatrists-psychologists
      versus nurses-caretakers were analysed using t-test. The analysis showed that
      intraclass correlations estimates of reliability of the HoNOSCA discharge scores
      were highest for ratings by child psychiatrists-psychologists and nurses
      caretakers. Analysis of ratings of patients with externalized and internalized
      disorders types showed differences in scoring disruptive/aggressive behaviours,
      self-care and family relationship scales. HoNOSCA had satisfactory inter-rater
      reliability in clinical multidisciplinary practice of child psychiatric inpatient
      unit. Implementing HoNOSCA in routine clinical practice and analysis of the
      rating differences among the multidisciplinary team members was useful to
      highlight possibilities for improvement of quality of services provided and
      building more constructive teamwork.

PMID- 18039296
TI  - The recovery alliance theory of mental health nursing.
AB  - The recovery alliance theory (RAT) is a mid-range theory of mental health nursing
      based on humanistic philosophy. The conception of the RAT was the outcome of
      collaboration among service users, practising mental health nurses,
      educationalists and managers and was developed in the context of a number of
      political and social changes as well as changes in the mental health field. The
      theory is composed of six constructs: humanistic philosophy, recovery,
      partnership relation, strengths focus, empowerment and common humanity. The
      derivation of three concepts from these constructs, namely coping, self
      responsibility/control and working alliance, forms the basis for the translation
      of the constructs into a system of mental health nursing practice [Partnership in
      Coping system (PinC)]. The constructs underpinning the RAT were clearly
      demonstrated in a preliminary trial of the PinC system.

PMID- 18039297
TI  - Experiences in a group of grown-up children of mentally ill parents.
AB  - Children of mentally ill parents have increased rates of psychopathology and
      reduced adaptive functioning. However, there are very few studies examining the
      subjective experiences of those children and their opinions concerning their
      previous contact with psychiatric services. This study followed up a group of
      children of former psychiatric inpatients by sending them a questionnaire asking
      about their experiences. Thirty-six individuals responded. Answers were analysed
      qualitatively by using manifest content analysis. Participants reported negative
      experiences and lack of information and support from psychiatric care. They had
      wanted more explanations and more support for themselves. Quantitative data are
      used to establish the significance of the results.

PMID- 18039298
TI  - Characteristics of patients who are violent to staff and towards other people
      from a community mental health service in South East England.
AB  - Professionals working in the public sector in the UK report widespread violence
      towards staff working in areas such as health care, social services and
      education. This study compares the characteristics of patients with and without a
      history of violence in a large sample of patients attending a community mental
      health service in South East England. The data were taken from a study of
      comorbidity and cannabis use in a mental health trust covering a semi-rural
      population of 250,000 people in Harlow and the surrounding area of South East
      England. Key workers were interviewed using semi-structured questionnaires from
      the Comorbidity of Substance Misuse and Mental illness in Community Mental Health
      and Substance Misuse Services study. Rates of violence against health workers
      were more than 20 times higher among those patients with a history of violence
      (23.6% vs. 1%, P<0.001). Alcohol and drug use was more frequent in those who were
      violent. Prevalence of comorbidity, schizophrenia and personality disorders was
      high. Key workers' estimates suggested that there was no difference in
      aggression, engagement or adherence to care plan among those with a history of
      violence.

PMID- 18039299
TI  - Nursing of young psychotic patients: analysis of work environments and attitudes.
AB  - Being members of the team who spend most of their time in direct contact with
      patient, nurses contribute considerably to observational and inpatient treatment
      process. The aims of this study were to analyse working environment of
      psychiatric nurses, attitudes, needs and emotional aspects while working with
      young (15-35 years old) psychotic patients. Study population consisted of
      psychiatric nurses working in all 15 inpatient psychiatry units in Vilnius.
      Nurses filled in an anonymous questionnaire. Summary statistics using number of
      observations, mean and SD were reported for quantitative variables, with absolute
      and relative frequencies for categorical variables. Questionnaires were filled by
      86 nurses. The mean working experience was 17 years in nursing and 14 years in
      psychiatric nursing. Data analysis revealed that majority of nurses rated their
      satisfaction with their job between average and high. Results showed that there
      was a lack of in-service training programmes. What especially difficult was
      nursing of young psychotic patients and required good professional knowledge,
      experience and individual approach to each patient. Majority of nurses were fully
      satisfied with their job and were interested in further continuous self
      education. The major concern in working with young psychotic patients was
      reassurance of personal and patient's safety.

PMID- 18039300
TI  - Finding the plot.

PMID- 18039301
TI  - Recovery and arts as activism.

PMID- 18039302
TI  - Living in the borderlands; writing in the margins: an autoethnographic tale.
AB  - A prerequisite to helping others is, arguably, some semblance of understanding of
      one's own self. But, how does one do self in a way that satisfies the integrity
      of psychotherapeutic theory, or the tenets of qualitative research? Moreover,
      what are the implications for the morally marginalized and uncertain in an era of
      epistemological and ontological certainty? These questions preface the raw data
      that constitutes the bulk of this paper: messy-text emails, reflections and
      comments from others, in relation to the breakdown experiences of two mental
      health academics/practitioners/teachers/supervisors. The methodology is
      autoethnography, thus the aim evocative. The textual presentation is in triple
      column form: in the first is the accounts of the protagonists, Short and Grant;
      the second contains reflections from friends and family, and the final is
      Clarke's pan-theoretical reflections on both.

PMID- 18039303
TI  - Experiences and constructions of art: a narrative-discourse analysis.
AB  - A narrative-discourse analysis was conducted to study the narratives of mental
      health service users talking about their engagement with art. The sample was
      drawn from a group of people who had attended arts workshops organized by a
      mental health service provider. Eleven people were interviewed and were asked to
      tell the story of their involvement in art and its significance to their lives.
      The data were analysed using a discourse analysis approach. Art is constructed as
      therapeutic within an illness repertoire. Emotions are inseparable from creative
      expression and identity claims are made in relation to being an artist.

PMID- 18039304
TI  - Catching life: the contribution of arts initiatives to recovery approaches in
      mental health.
AB  - This paper draws on a qualitative study that was undertaken as part of a national
      research study to assess the impact of participatory arts provision for people
      with mental health needs. It explores how arts and mental health projects may
      facilitate some of the key elements of what has been termed a 'recovery approach'
      in mental health. It is argued that it is precisely these elements--the fostering
      of hope, creating a sense of meaning and purpose, developing new coping
      mechanisms and rebuilding identities--which are hard to standardize and measure,
      yet may be the most profound and significant outcomes of participation in such
      projects. Therefore, in the context of a growing emphasis on recovery-orientated
      mental health services, while not necessarily being appropriate for all service
      users, arts and mental health initiatives could make an essential contribution to
      the future of mental health and social care provision.

PMID- 18039305
TI  - Lifeworld, the arts and mental health nursing.
AB  - Various manifestations of the arts have been employed in mental health care as
      successful diversional and therapeutic interventions, and as an adjunct to mental
      healthcare professional education. There is now a current groundswell of the use
      of the arts and humanities in both the practice of research and the
      representation and dissemination of findings. Here, we first point to the
      potential ability of the arts that can be used to re-humanize the world of health
      and social care and its underpinning sciences. Second, we highlight the nature
      and relevance of this more aesthetic movement and its potential to enable
      meaningful engagement with people in order to facilitate shared understandings of
      concretely lived experiences. Finally, we use a long-standing philosophical
      framework, the 'lifeworld', as an exemplar to demonstrate how the wholeness and
      essence of human being can be revealed or shown through art. In doing so, we make
      the tentative suggestion that phenomenology and the lifeworld approach may be a
      useful philosophical framework for underpinning the use of arts in mental health
      nursing.

PMID- 18039306
TI  - Seeing the psychiatrist: an autoethnographic account.
AB  - Autoethnography is a fairly recent approach to ethnography and one in which the
      writer becomes the 'subject' of the study. It remains an approach under question
      until more has been done in the field. In this account, I describe attending an
      interview with a psychiatrist, as a patient. I map out the process I encountered
      and offer, alongside the map, various critical and reflective comments. I offer a
      summary of my 'findings' and close with a critical evaluation both of the method
      and of the paper. Findings included: a comfortable and comforting 'setting up' of
      the interview; a sense of moving into the 'patient role'; a clear indication of
      how the interview would proceed; and empathic manner on the part of the
      psychiatrist and a sound process of follow-through with my general practitioner.
      In the critique section, I try to answer the question as to whether or not
      authoethnography is self-indulgent and the degree to which it can or cannot help
      others in understanding mental health issues. I remain uncertain about both the
      method and its value. In the end, it is probably for the reader to answer these
      questions.

PMID- 18039307
TI  - People in glass houses.

PMID- 18039316
TI  - Limitation of myocardial and endothelial injury of the rat heart graft after
      preservation with Centre de Resonance Magnetique Biologique et Medicale (CRMB)
      solution.
AB  - Myocardial injury caused by prolonged storage compromises post-transplantation
      contractile performance and induces endothelial injury. The aim of this study was
      to compare a solution developed in our laboratory [Centre de Resonance Magnetique
      Biologique et Medicale (CRMBM) solution] with a widely used solution (Celsior,
      Genzyme, Saint Germain en Laye, France). Metabolic and contractile parameters as
      well as indexes of endothelial injury were measured in a heterotopic rat heart
      transplantation model with a 3-h ischaemia and a 1-h reperfusion. The two
      solutions were randomly used for cardioplegia and graft preservation in six
      experiments each. During reperfusion, developed pressure and rate pressure
      product were higher with CRMBM compared with Celsior (P = 0.0002 and P = 0.0135,
      respectively). Phosphocreatine and adenosine triphosphate (ATP) concentrations
      after reperfusion were significantly higher with CRMBM (P = 0.0069 and P =
      0.0053, respectively). Endothelial nitric oxide synthase (eNOS) and neuronal
      nitric oxide synthase (nNOS) protein expression were decreased to the same extent
      after reperfusion compared with baseline with CRMBM (P = 0.0001 and P < 0.0001,
      respectively) and Celsior (P = 0.0007 and P < 0.0001, respectively). Total
      nitrate concentration (NOx) was significantly increased after reperfusion with
      CRMBM (P < 0.0001 versus baseline and P < 0.0001 versus Celsior). Na,K-ATPase
      activity was decreased in both groups versus baseline after reperfusion (P <
      0.0001 for CRMBM and P < 0.0001 for Celsior). We showed limitation of both
      myocardial and endothelial damage with CRMBM compared with Celsior during
      heterotopic rat heart transplantation in vivo.

PMID- 18039317
TI  - Expected number of deaths in the liver transplantation waiting list in the state
      of Sao Paulo, Brazil.

PMID- 18039318
TI  - Unexpected low incidence of vertebral fractures in heart transplant recipients:
      analysis of bone turnover.
AB  - Heart transplantation (HTX) is associated with a reduction in bone mineral
      density (BMD). Different markers of bone metabolism have been used, and the
      applied immunosuppressive regimens have also changed over time. This study was
      performed to re-investigate bone metabolism in HTX recipients. Twenty-five HTX
      recipients were compared with 25 HTX candidates in respect of biochemical
      parameters of bone metabolism, BMD, and the frequency of fractures for 1 year.
      Osteopenia or osteoporosis was observed in approximately two-thirds of the HTX
      recipients. Nevertheless, only three (12%) HTX recipients developed a vertebral
      fracture within 1 year after transplantation; no peripheral fractures occurred.
      Compared with HTX candidates, HTX recipients had lower serum levels of
      osteocalcin, and higher serum levels of cross-linked-N-telopeptide of type I
      collagen (NTX). In HTX recipients, osteocalcin initially reached a nadir,
      increased during the first 3 months, and decreased thereafter. Bone-specific
      alkaline phosphatase initially increased and then decreased. Serum levels of NTX
      and parathyroid hormone remained high throughout the year. Despite a high bone
      turnover, an unexpectedly low rate of vertebral fractures was registered.
      Nevertheless, each fragility fracture is a serious complication and we need to
      take steps to prevent this complication.

PMID- 18039319
TI  - Routine fetal RHD genotyping with maternal plasma: a four-year experience in
      Belgium.
AB  - BACKGROUND: The objective was to evaluate the diagnostic value of RHD fetal
      genotyping from the plasma of D- mothers as soon as 10 weeks' gestation in a
      routine clinical practice in Belgium. STUDY DESIGN AND METHODS: A prospective
      study was conducted between November 2002 and December 2006. DNA extraction was
      performed in an automated closed tube system. Fetal RHD/SRY genotypes were
      detected in the plasma of 563 pregnant mothers by real-time polymerase chain
      reaction (PCR) targeting multiple exons 4, 5, and 10 of the RHD gene and
      targeting an SRY gene sequence. These were compared to the D phenotypes
      determined in the 581 babies they delivered. RESULTS: By combining amplification
      of three exons, the concordance rate of fetal RHD genotypes in maternal plasma
      and newborn D phenotypes at delivery was 100 percent (99.8% including one unusual
      false-positive). The presence of nonfunctional RHD genes and the absence of a
      universal fetal marker, irrespective of fetal sex, did not influence the accuracy
      of fetal RhD status prediction. The RHD genotyping from 18 twin pregnancies was
      also assessed. Five weak D women were excluded from the RHD fetal genotyping
      prediction. Three discrepant results (0.5%) between predicted fetal genotype and
      cord blood phenotype were not confirmed by the baby phenotypes from venipuncture
      blood. CONCLUSION: Prenatal prediction of fetal RHD by targeting multiple exons
      from the maternal plasma with real-time PCR is highly sensitive and accurate.
      Over 4 years, this experience has highly modified our management of D- pregnant
      women.

PMID- 18039320
TI  - Tfm-AR modulates the effects of ApoE4 on cognition.
AB  - Female mice are more susceptible to apolipoprotein E (apoE4)-induced cognitive
      deficits than male mice. These deficits can be antagonized by stimulating
      androgen receptors (ARs). To determine the role of AR in the cognitive effects of
      apoE4, we backcrossed mutant mice with a naturally occurring defect in the AR
      [testicular feminization mutant (tfm)] onto the Apoe-/- background to eliminate
      mouse apoE gene resulting in non-functional AR, and crossed the tfm/Apoe-/-
      female mice with apoE4 transgenic male mice. We behaviorally compared Apoe-/-,
      apoE4, tfm, and tfm/apoE4 male mice. Apoe-/-, apoE4, and tfm mice showed
      hippocampus-dependent novel location recognition but tfm/apoE4 mice did not. In
      contrast, all groups showed hippocampus-independent novel object recognition.
      Hippocampus-dependent learning and memory were also assessed in the water maze.
      In the water maze probe trial following the second day of hidden platform
      training, Apoe-/- and apoE4 mice showed spatial memory retention, but tfm and
      tfm/ApoE4 mice did not. In the water maze, probe trial following the third day of
      hidden platform training, Apoe-/-, apoE4, and tfm/Apoe-/- mice showed spatial
      memory retention, but tfm mice did not. These data support an important role for
      AR in protecting against the detrimental effects of apoE4 on hippocampus
      dependent learning and memory.

PMID- 18039321
TI  - Density-dependent recruitment in grassland small mammals.
AB  - 1. Density dependence has an important influence on the dynamics of many species
      of small mammals. To regulate population growth, density must affect negatively a
      vital rate (e.g. fecundity); however, little is known about which vital rates are
      most affected by density. 2. We used a long-term data set for five species of
      rodents from north-eastern Kansas, USA to test for relationships between density
      and the proportion of pregnant females, per capita fecundity and recruitment. We
      estimated proportion of pregnant females using data collected in the field and
      fecundity using data on survival, proportion of pregnant females and literature
      based density-dependent litter size for each species. We used reverse capture
      histories to estimate per-capita recruitment. 3. The proportion of pregnant
      females was related positively to density in most species. Fecundity was related
      negatively to density in the cotton rat (Sigmodon hispidus Say & Ord, 1825) and
      not related to density in the four remaining species. Recruitment was related
      negatively to density in all five species, although not all relationships were
      statistically significant. 4. The signature of density-dependent recruitment was
      strongest in the prairie vole [Microtus ochrogaster (Wagner, 1842)] and cotton
      rat and less so in the remaining species. 5. Our analyses indicate that density
      affects recruitment negatively in grassland small mammals either through a
      reduction in immigration or reduced survival of nestlings. Models that seek to
      include empirical estimates of density dependence may need to include immigration
      in addition to survival and fecundity.

PMID- 18039322
TI  - The interactive effects of parasites, disturbance, and productivity on
      experimental adaptive radiations.
AB  - Disturbance, productivity, and natural enemies are significant determinants of
      the evolution of diversity, but their interactive effect remains unresolved. We
      develop a simple, qualitative model assuming trade-offs between growth rate,
      competitive ability and parasite resistance, to address the interactive effects
      of these variables on the evolution of host diversity. Consistent with previous
      studies our model predicts maximum diversity at intermediate levels of
      disturbance and productivity in the absence of parasitism. However, parasites
      break down these unimodal diversity relationships with productivity and
      disturbance, as selection for parasite resistance reduces the importance of
      growth rate-competitive ability trade-offs. We tested these predictions using the
      bacterium Pseudomonas fluorescens, which undergoes an adaptive radiation into
      spatial niche specialists under laboratory conditions. This is the first study of
      adaptive radiation in response to experimental manipulation of the three-way
      interaction between productivity, disturbance, and natural enemies. As
      hypothesized, unimodal diversity relationships with disturbance and productivity
      were weakened or disappeared in the presence of parasitic phages. This was the
      result of phages increasing diversity at environmental extremes, by imposing
      selection for phage-resistant variants, but decreasing diversity in less
      stressful environments, probably through reductions in resource competition.
      Phages had a net effect of increasing host diversity. Parasites and other natural
      enemies are therefore likely to have a large effect in mitigating the influence
      of other environmental variables on the evolution and maintenance of diversity.

PMID- 18039323
TI  - The rate of genome stabilization in homoploid hybrid species.
AB  - Homoploid hybrid speciation has been recognized for its potential rapid
      completion, an idea that has received support from experimental and modeling
      studies. Following initial hybridization, the genomes of parental species
      recombine and junctions between chromosomal blocks of different parental origin
      leave a record of recombination and the time period before homogenization of the
      derived genome. We use detailed genetic maps of three hybrid species of
      sunflowers and models to estimate the time required for the stabilization of the
      new hybrid genome. In contrast to previous estimates of 60 or fewer generations,
      we find that the genomes of three hybrid sunflower species were not stabilized
      for hundreds of generations. These results are reconciled with previous research
      by recognizing that the stabilization of a hybrid species' genome is not
      synonymous with hybrid speciation. Segregating factors that contribute to initial
      ecological or intrinsic genetic isolation may become stabilized quickly. The
      remainder of the genome likely becomes stabilized over a longer time interval,
      with recombination and drift dictating the contributions of the parental genomes.
      Our modeling of genome stabilization provides an upper bound for the time
      interval for reproductive isolation to be established and confirms the rapid
      nature of homoploid hybrid speciation.

PMID- 18039324
TI  - The evolution of restraint in bacterial biofilms under nontransitive competition.
AB  - Theoretical and empirical evidence indicates that competing species can coexist
      if dispersal, migration, and competitive interactions occur over relatively small
      spatial scales. In particular, spatial structure appears to be critical to
      certain communities with nontransitive competition. A typical nontransitive
      system involves three competing species that satisfy a relationship similar to
      the children's game of rock-paper-scissors. Although the ecological dynamics of
      nontransitive systems in spatially structured communities have received some
      attention, fewer studies have incorporated evolutionary change. Here we
      investigate evolution within toxic bacterial biofilms using an agent-based
      simulation that represents a nontransitive community containing three populations
      of Escherichia coli. In structured, nontransitive communities, strains evolve
      that do not maximize their competitive ability: They do not reduce their
      probability of death to a minimum or increase their toxicity to a maximum. That
      is, types evolve that exercise restraint. We show that nontransitivity and
      spatial structure (in the form of localized interactions) are both necessary for
      the evolution of restraint in these biofilms.

PMID- 18039325
TI  - Rapid parasite adaptation drives selection for high recombination rates.
AB  - The Red Queen hypothesis proposes that sex is maintained through selection
      pressure imposed by coevolving parasites: susceptible hosts are able to escape
      parasite pressure by recombining their genome to create resistant offspring.
      However, previous theoretical studies have shown that the Red Queen typically
      selects against sex unless selection is strong, arguing that high rates of
      recombination cannot evolve when parasites are of low virulence. Here we show
      that under the biologically plausible assumption of a severe fitness cost for
      parasites that fail to infect, the Red Queen can cause selection for high
      recombination rates, and that the strength of virulence is largely irrelevant to
      the direction of selection for increased recombination rates. Strong selection on
      parasites and short generation times make parasites usually better adapted to
      their hosts than vice versa and can thus favor higher recombination rates in
      hosts. By demonstrating the importance of host-imposed selection on parasites,
      our findings resolve previously reported conflicting results.

PMID- 18039327
TI  - Genetic, morphological, and ecological characterization of a hybrid zone that
      spans a migratory divide.
AB  - This study characterizes a hybrid zone that spans a migratory divide between
      subspecies of the Swainson's thrush (Catharus ustulatus), a long distance
      migratory songbird, in the Coast Mountains of British Columbia. To assess the
      potential for a barrier to gene flow between the subspecies, I: (1) analyzed the
      shape and width of genetic and morphological clines relative to estimates of
      dispersal distance, (2) assessed the ratio of parental to hybrid genotypes across
      the hybrid zone, (3) estimated population density across the hybrid zone, and (4)
      compared the spatial relationship between the hybrid zone and an existing
      environmental gradient. The results indicate that the hybrid zone is
      characterized by mostly concordant character clines that are narrow relative to
      dispersal, the absence of a hybrid swarm, and low population density at the
      center of the zone. This hybrid zone and additional regions of contact between
      these subspecies are found on the border between coastal and interior climatic
      regions throughout the Pacific Northwest. An identified shift in the location,
      but not the width, of the mtDNA cline relative to the nuclear clines is
      consistent with asymmetrical hybridization. Neutral diffusion of populations
      following secondary contact and hybrid superiority within an ecotone are
      insufficient explanations for the observed patterns. The hypothesis that best
      fits the data is that the Swainson's thrush hybrid zone is a tension zone
      maintained by dispersal and ecologically mediated barriers to gene flow.

PMID- 18039328
TI  - Sperm motility in Mytilus edulis in relation to mitochondrial DNA polymorphisms:
      implications for the evolution of doubly uniparental inheritance in bivalves.
AB  - Bivalves of the families Mytilidae, Unionidae, and Veneridae have an unusual mode
      of mitochondrial DNA (mtDNA) transmission called doubly uniparental inheritance
      (DUI). A characteristic feature of DUI is the presence of two gender-associated
      mtDNA genomes that are transmitted through males (M-type mtDNA) and females (F
      type mtDNA), respectively. Female mussels are predominantly homoplasmic with only
      the F-type expressed in both somatic and gonadal tissue; males are heteroplasmic
      with the M-type expressed in the gonad and F-type in somatic tissue for the most
      part. An unusual evolutionary feature of this system is that an mt genome with F
      coding sequences occasionally invades the male route of inheritance (i.e., a
      "role reversal" event), and is thereafter transmitted as a new M-type.
      Phylogenetic studies have demonstrated that the new or "recently masculinized" M
      types may eventually replace the older or "standard" M-types over time. To
      investigate whether this replacement process could be due to an advantage in
      sperm swimming behavior, we measured differences in motility parameters and found
      that sperm with the recently masculinized M-type had significantly faster
      curvilinear velocity and average path velocity when compared to sperm with
      standard M-type. This increase in sperm swimming speed could explain the multiple
      evolutionary replacements of standard M-types by masculinized M-types that have
      been hypothesized for the mytilid lineage. However, our observations do not
      support the hypothesis that DUI originated because it permits the evolution of
      mitochondrial adaptations specific to sperm performance, otherwise, the
      evolutionarily older, standard M genome should perform better.

PMID- 18039326
TI  - Rapid adaptive divergence in new world achillea, an autopolyploid complex of
      ecological races.
AB  - Adaptive evolution is often associated with speciation. In plants, however,
      ecotypic differentiation is common within widespread species, suggesting that
      climatic and edaphic specialization can outpace cladogenesis and the evolution of
      postzygotic reproductive isolation. We used cpDNA sequence (5 noncoding regions,
      3.5 kb) and amplified fragment length polymorphisms (AFLPs: 4 primer pairs, 1,013
      loci) to evaluate the history of ecological differentiation in the North American
      Achillea millefolium, an autopolyploid complex of "ecological races" exhibiting
      morphological, physiological, and life-history adaptations to diverse
      environments. Phylogenetic analyses reveal North American A. millefolium to be a
      monophyletic group distinct from its European and Asian relatives. Based on
      patterns of sequence divergence, as well as fossil and paleoecological data,
      colonization of North America appears to have occurred via the Bering Land Bridge
      during the Pleistocene (1.8 MYA to 11,500 years ago). Population genetic analyses
      indicate negligible structure within North American A. millefolium associated
      with varietal identity, geographic distribution, or ploidy level. North American
      populations, moreover, exhibit the signature of demographic expansion. These
      results affirm the "ecotype" concept of the North American Achillea advocated by
      classical research and demonstrate the rapid rate of ecological differentiation
      that sometimes occurs in plants.

PMID- 18039329
TI  - Phylogenetic and geographic variation in host breadth and composition by
      herbivorous amphipods in the family Ampithoidae.
AB  - Predicting the host range for herbivores has been a major aim of research into
      plant-herbivore interactions and an important model system for understanding the
      evolution of feeding specialization. Among many terrestrial insects, host range
      is strongly affected by herbivore phylogeny and long historical associations
      between particular herbivore and plant taxa. For small herbivores in marine
      environments, it is known that the evolution of host use is sculpted by several
      ecological factors (e.g., food quality, value as a refuge from predators, and
      abiotic forces), but the potential for phylogenetic constraints on host use
      remains largely unexplored. Here, we analyze reports of host use of herbivorous
      amphipods from the family Ampithoidae (102 amphipod species from 12 genera) to
      test the hypotheses that host breadth and composition vary among herbivore
      lineages, and to quantify the extent to which nonpolar secondary metabolites
      mediate these patterns. The family as a whole, and most individual species, are
      found on a wide variety of macroalgae and seagrasses. Despite this polyphagous
      host use, amphipod genera consistently differed in host range and composition. As
      an example, the genus Peramphithoe rarely use available macrophytes in the order
      Dictyotales (e.g., Dictyota) and as a consequence, display a more restricted host
      range than do other genera (e.g., Ampithoe, Cymadusa, or Exampithoe). The strong
      phylogenetic effect on host use was independent of the uneven distribution of
      host taxa among geographic regions. Algae that produced nonpolar secondary
      metabolites were colonized by higher numbers of amphipod species relative to
      chemically poor genera, consistent with the notion that secondary metabolites do
      not provide algae an escape from amphipod herbivory. In contrast to patterns
      described for some groups of phytophagous insects, marine amphipods that use
      chemically rich algae tended to have broader, not narrower, host ranges. This
      result suggests that an evolutionary advantage to metabolite tolerance in marine
      amphipods may be that it increases the availability of appropriate algal hosts
      (i.e., enlarges the resource base).

PMID- 18039330
TI  - The health status burden of people with fibromyalgia: a review of studies that
      assessed health status with the SF-36 or the SF-12.
AB  - OBJECTIVE: The current review describes how the health status profile of people
      with fibromyalgia (FM) compares to that of people in the general population and
      patients with other health conditions. METHODS: A review of 37 studies of FM that
      measured health status with the 36-item Medical Outcomes Study Short-Form Health
      Survey (SF-36) or the 12-item Short-Form Health Survey (SF-12). RESULTS: Studies
      performed worldwide showed that FM groups were significantly more impaired than
      people in the general population on all eight health status domains assessed.
      These domains include physical functioning, role functioning difficulties caused
      by physical problems, bodily pain, general health, vitality (energy vs. fatigue),
      social functioning, role functioning difficulties caused by emotional problems
      and mental health. FM groups had mental health summary scores that fell 1
      standard deviation (SD) below the general population mean, and physical health
      summary scores that fell 2 SD below the general population mean. FM groups also
      had a poorer overall health status compared to those with other specific pain
      conditions. FM groups had similar or significantly lower (poorer) physical and
      mental health status scores compared to those with rheumatoid arthritis,
      osteoarthritis, osteoporosis, systemic lupus erythematosus, myofacial pain
      syndrome, primary Sjogren's syndrome and others. FM groups scored significantly
      lower than the pain condition groups mentioned above on domains of bodily pain
      and vitality. Health status impairments in pain and vitality are consistent with
      core features of FM. CONCLUSIONS: People with FM had an overall health status
      burden that was greater in magnitude compared to people with other specific pain
      conditions that are widely accepted as impairing.

PMID- 18039332
TI  - The effect of heme on the conformational stability of micro-myoglobin.
AB  - Micro-myoglobin, the isolated heme-binding subdomain of myoglobin, is a valuable
      model system for the investigation of heme recognition and binding by proteins,
      and provides an example of protein folding induced by cofactor binding.
      Theoretical studies by molecular dynamics simulations on apo- and holo-micro
      myoglobin show that, by contrast with the case of the full-length wild-type
      protein and in agreement with earlier experimental evidence, the apo-protein is
      not stably folded in a native-like conformation. With the cofactor bound,
      however, the protein fragment maintains its folded conformation over 1.5 ns in
      molecular dynamics simulations. Further inspection of the model structures
      reveals that the role of heme in stabilizing the folded state is not only a
      result of its direct interactions with binding residues (His93, Arg45 and Lys96),
      but also derives from its shielding effect on a long-range electrostatic
      interaction between Arg45 and Asp60, which, in the molecular dynamics
      simulations, apparently triggers the unfolding process of apo-micro-myoglobin.

PMID- 18039331
TI  - Human retinol dehydrogenase 13 (RDH13) is a mitochondrial short-chain
      dehydrogenase/reductase with a retinaldehyde reductase activity.
AB  - Retinol dehydrogenase 13 (RDH13) is a recently identified short-chain
      dehydrogenase/reductase related to microsomal retinoid oxidoreductase RDH11. In
      this study, we examined the distribution of RDH13 in human tissues, determined
      its subcellular localization and characterized the substrate and cofactor
      specificity of purified RDH13 in order to better understand its properties. The
      results of this study demonstrate that RDH13 exhibits a wide tissue distribution
      and, by contrast with other members of the RDH11-like group of short-chain
      dehydrogenases/reductases, is a mitochondrial rather than a microsomal protein.
      Protease protection assays suggest that RDH13 is localized on the outer side of
      the inner mitochondrial membrane. Kinetic analysis of the purified protein shows
      that RDH13 is catalytically active and recognizes retinoids as substrates.
      Similar to the microsomal RDHs, RDH11, RDH12 and RDH14, RDH13 exhibits a much
      lower Km value for NADPH than for NADH and has a greater catalytic efficiency in
      the reductive than in the oxidative direction. The localization of RDH13 at the
      entrance to the mitochondrial matrix suggests that it may function to protect
      mitochondria against oxidative stress associated with the highly reactive
      retinaldehyde produced from dietary beta-carotene.

PMID- 18039333
TI  - Light optical precision measurements of the active and inactive Prader-Willi
      syndrome imprinted regions in human cell nuclei.
AB  - Despite the major advancements during the last decade with respect to both
      knowledge of higher order chromatin organization in the cell nucleus and the
      elucidation of epigenetic mechanisms of gene control, the true three-dimensional
      (3D) chromatin structure of endogenous active and inactive gene loci is not
      known. The present study was initiated as an attempt to close this gap. As a
      model case, we compared the chromatin architecture between the genetically active
      and inactive domains of the imprinted Prader-Willi syndrome (PWS) locus in human
      fibroblast and lymphoblastoid cell nuclei by 3D fluorescence in situ
      hybridization and quantitative confocal laser scanning microscopy. The volumes
      and 3D compactions of identified maternal and paternal PWS domains were
      determined in stacks of light optical serial sections using a novel threshold
      independent approach. Our failure to detect volume and compaction differences
      indicates that possible differences are below the limits of light optical
      resolution. To overcome this limitation, spectral precision distance microscopy,
      a method of localization microscopy at the nanometer scale, was used to measure
      3D distances between differentially labeled probes located both within the PWS
      region and in its neighborhood. This approach allows the detection of
      intranuclear differences between 3D distances down to about 70-90 nm, but again
      did not reveal clearly detectable differences between active and inactive PWS
      domains. Despite this failure, a comparison of the experimental 3D distance
      measurements with computer simulations of chromatin folding strongly supports a
      non-random higher order chromatin configuration of the PWS locus and argues
      against 3D configurations based on giant chromatin loops. Our results indicate
      that the search for differences between endogenous active and inactive PWS
      domains must be continued at still smaller scales than hitherto possible with
      conventional light microscopic procedures. The possibilities to achieve this goal
      are discussed.

PMID- 18039334
TI  - Healing at fluoride-modified implants placed in wide marginal defects: an
      experimental study in dogs.
AB  - OBJECTIVE: To study the healing at fluoride-modified implants placed in wide
      circumferential defects. MATERIAL AND METHODS: Six mongrel dogs were used. The
      mandibular premolars and first molars were extracted. Three months later four
      implants were placed in one side of the mandible of each dog. The control
      implants (MicroThread) had a TiOblast surface, while the test implants
      (OsseoSpeed) had a fluoride-modified surface. Two implants of each type were
      placed. The marginal 50% of the prepared canal was widened using step drills.
      Following installation a 1 mm wide gap occurred between the implant surface and
      the bone wall in the defect. All implants were submerged. The installation
      procedure was repeated in the opposite side of the mandible 4 weeks after the
      first implant surgery. Two weeks later the animals were euthanized and block
      biopsies containing the implant and surrounding tissues were prepared for
      histological analysis. RESULTS: The histological analysis revealed that a
      significantly larger area of osseointegration was established within the defect
      at fluoride-modified implants than at implants with a TiOblast surface after 6
      weeks of healing. Further, the degree of bone-to-implant contact within the
      defect area was larger at fluoride-modified implants than at the TiOblast
      implants. CONCLUSION: It is suggested that the fluoride-modified implant surface
      promotes bone formation and osseointegration.

PMID- 18039335
TI  - Multivariate study of factors influencing primary dental implant stability.
AB  - OBJECTIVES: The purpose was to determine by multivariate analysis in a large
      series of dental implants the variables associated with primary endosseous dental
      implant stability (DIS). MATERIAL AND METHODS: A 10-year retrospective study was
      conducted of 1084 Branemark implants placed in 316 patients. Clinical variables
      (age, gender, smoking habit, and periodontal status), implant diameter, implant
      length, and Periotest values (PTVs) were analyzed in bivariate and multivariate
      studies in order to determine their influence on DIS, using a cut-off PTV value
      of -2. RESULTS: The site of implant insertion showed the strongest association
      with primary DIS failure among the study variables. Implants in the anterior
      mandible had a 6.43-fold lower risk of primary DIS risk vs. those at other sites
      [95% confidence interval (CI) 3.28-12.61], and implants in the maxillary had a
      2.70-fold higher risk of primary DIS failure vs. those in the mandible (95% CI
      1.82-4). Among other variables, females had a 1.54-fold higher risk of primary
      DIS failure vs. males (95% CI 1.88-2.22) and implants <15 mm in length had a 1.49
      fold higher risk of failure vs. longer implants (95% CI 1.09-2.04). CONCLUSION:
      According to these findings, primary DIS failure is more likely in females, at
      sites other than the anterior mandible, and with dental implants shorter than 15
      mm, at least when non-threaded titanium implants are used. These data may be of
      value in the identification of patients at a high risk of primary DIS failure
      with immediate implant loading.

PMID- 18039336
TI  - Re-osseointegration on rough implant surfaces previously coated with bacterial
      biofilm: an experimental study in the dog.
AB  - OBJECTIVE: The purpose of the study was to investigate whether osseointegration
      can occur on rough implant surfaces that previously had been coated with
      bacterial biofilm. MATERIALS AND METHODS: The premolars on both sides of the
      mandible in four beagle dogs were extracted. Following 3 months healing, three
      titanium implants Ti-Unite, Nobel Biocare were partially inserted in the left
      side of each mandible. Some threads protruded from the tissues into the oral
      cavity. Plaque accumulated on the exposed part of the implant. Following a 5-week
      healing period, the contaminated parts of each implant were treated using three
      different techniques: (1) swabbing with citric acid for 30 s followed by rinsing
      with physiological saline, (2) cleansing with a toothbrush and physiological
      saline for 1 min, and (3) swabbing with 10% hydrogen peroxide for 1 min followed
      by rinsing with physiological saline. The treated implants and one pristine
      implant (control) were installed to the full implant length on the contralateral
      sides of the mandibles. Following 11 weeks of healing, the dogs were sacrificed
      and biopsies were obtained. Ground sections were prepared for histomorphometric
      analysis. RESULTS: All treatment modalities were associated with direct bone-to
      implant contact on the portion of implant surface previously exposed to the oral
      environment. CONCLUSIONS: The results demonstrate that rough surfaces, which were
      plaque contaminated and cleaned by different methods, can re-osseointegrate.

PMID- 18039337
TI  - Bone healing dynamics at buccal peri-implant sites.
AB  - BACKGROUND: It is common belief that immediate implant placement into extraction
      sites may act to preserve the alveolar process. The objective of this study was
      to evaluate healing dynamics at buccal peri-implant sites in relation to the
      dimensions of the alveolar ridge. METHODS: Bilateral, critical-size,
      supraalveolar, peri-implant defects were created in 12 male Hound Labrador
      mongrel dogs following surgical horizontal cut-down of the alveolar ridge. Each
      jaw quadrant received three 10-mm titanium implants placed 5 mm into extraction
      sites of the third and fourth premolar teeth leaving 5 mm in a supraalveolar
      position. The mucoperiosteal flaps were advanced, adapted, and sutured for
      primary intention healing. Bone fluorescent markers were administered at weeks 3
      and 4 postsurgery, and pre-euthanasia. Incandescent, polarized, and fluorescent
      light microscopies were used to assess the width of the buccal wall of the
      alveolar ridge and local bone remodeling over the 8-week healing interval.
      RESULTS: There was a significant association between the width of the buccal
      alveolar ridge and extent of bone resorption evaluated by incandescent and
      fluorescent light microscopy. A non-linear association was observed between the
      buccal ridge width and resorption of the alveolar ridge. A 2-mm threshold was
      established to account for this non-linearity. The strength of this association
      was two times greater in specimens with a buccal ridge width <2 mm compared with
      a wider ridge (beta=1.62 vs. 0.80) observed by fluorescent light microscopy.
      Accordingly, mean buccal resorption was significantly greater when the ridge
      width was <2 mm. Fluorescent light microscopy consistently showed greater buccal
      resorption compared with incandescent light microscopy (P<0.05). Agreement
      between the examination techniques was low (concordance correlation
      coefficient=0.49), especially for higher values of buccal resorption. CONCLUSION:
      When implants are placed into extraction sites, proximity to the buccal alveolar
      crest appears a major consideration. The observations herein suggest that the
      width of the buccal alveolar ridge should be at least 2 mm to maintain the
      alveolar bone level. These observations likely have general implications for
      implant placement using most surgical protocols.

PMID- 18039338
TI  - SMILE: first observational prospective cohort study of migraine in primary care
      in France. Description of methods and study population.
AB  - The SMILE study was conducted among migraine patients consulting in primary care
      in France. The first phase aimed to describe the study sample of patients at
      entry to the study, especially emotional dimension (Hospital Anxiety and
      Depression scale), functional impact (abridged Migraine Specific Questionnaire),
      stress (Perceived Stress Scale) and coping behaviours (brief COPE inventory
      avoidance subscale, Coping Strategies Questionnaire catastrophizing subscale), as
      well as treatments used and their effectiveness and treatments prescribed at end
      of consultation. Results indicate that consulting migraine patients suffer
      frequent migraine attacks, exhibit substantial levels of anxiety, functional
      impact and stress, and often use maladaptive coping strategies. Abortive
      treatments appear ineffective in most patients (74%). Patients with more affected
      psychometric variables and treatment ineffectiveness are more likely to be deemed
      eligible for prophylactic treatment. These data highlight the seriousness of
      migraine and maladjustment of patients consulting in primary care.

PMID- 18039339
TI  - Prednisone vs. placebo in withdrawal therapy following medication overuse
      headache.
AB  - This proof-of-concept study evaluated the efficacy of prednisone for the
      treatment of withdrawal symptoms in patients with medication overuse headache
      (MOH) in a randomized, placebo-controlled, double-blind design. Twenty patients
      were randomized and underwent in-patient withdrawal therapy. The total number of
      hours with severe or moderate headache within the first 72 and 120 h was
      significantly lower in the prednisone group. The results show that prednisone
      might be effective in the treatment of medication withdrawal headache.

PMID- 18039340
TI  - Efficacy of pregabalin in the treatment of trigeminal neuralgia.
AB  - This prospective, open-label study aimed to evaluate the efficacy of pregabalin
      treatment in patients suffering from trigeminal neuralgia with and without
      concomitant facial pain. Fifty-three patients with trigeminal neuralgia (14 with
      concomitant chronic facial pain) received pregabalin (PGB) 150-600 mg daily and
      were prospectively followed for 1 year. The primary outcome was number of
      patients pain free or with reduction of pain intensity by > 50% and of attack
      frequency by > 50% after 8 weeks. Secondary outcome was sustained pain relief
      after 1 year. Thirty-nine patients (74%) improved after 8 weeks with a mean dose
      of 269.8 mg/day (range 150-600 mg/day) PGB: 13 (25%) experienced complete pain
      relief and 26 (49%) reported pain reduction > 50%, whereas 14 (26%) did not
      improve. Patients without concomitant facial pain showed better response rates
      (32 of 39, 82%) compared with patients with concomitant chronic facial pain (7 of
      14, 50%, P = 0.020). Concomitant chronic facial pain appears to be a clinical
      predictor of poor treatment outcome. PGB appears to be effective in the treatment
      of trigeminal neuralgia.

PMID- 18039341
TI  - Dissecting cellulitis of the scalp responding to oral quinolones.

PMID- 18039342
TI  - Successful treatment of palmoplantar arsenical keratosis with a combination of
      keratolytics and low-dose acitretin.

PMID- 18039343
TI  - Florid hyperplastic folliculitis on the chin in a male renal transplant patient.

PMID- 18039344
TI  - Cellulitis due to Myroides odoratimimus in a patient with alcoholic cirrhosis.

PMID- 18039345
TI  - Choroidal perfusion in eyes with untreated choroidal melanoma.
AB  - PURPOSE: Previous studies indicate that ocular blood flow is altered in eyes with
      choroidal melanoma. In the present study pulsatile ocular blood flow (POBF) was
      assessed to investigate whether there exists a correlation between tumour size
      and ocular blood flow parameters. METHODS: Twenty-two patients with unilateral
      untreated choroidal melanoma were studied using two measurement techniques: POBF
      was measured with a pneumotonometer and local foveal fundus pulsation amplitude
      (FPA) by laser interferometry, and results were correlated. Tumour volume was
      calculated using the ellipsoidal solid model and was correlated to POBF and FPA.
      RESULTS: Levels of POBF and FPAs tended to be higher in tumour eyes compared with
      unaffected eyes, but the differences did not reach the level of significance.
      Both methods showed a high degree of correlation in unaffected eyes. In tumour
      eyes the correlation was slightly less pronounced. There was no correlation
      between tumour and POBF or FPA. CONCLUSIONS: Our results do not indicate
      choroidal hyperperfusion in patients with choroidal melanoma. The clinical
      usefulness of measuring POBF in tumour patients may be limited.

PMID- 18039346
TI  - Visual prognosis and vitreous cytokine levels after arteriovenous sheathotomy in
      branch retinal vein occlusion associated with macular oedema.
AB  - PURPOSE: To investigate the relationship between vitreous levels of cytokines,
      including interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), and
      visual prognosis after pars plana vitrectomy (PPV) with arteriovenous sheathotomy
      in patients with branch retinal vein occlusion (BRVO) associated with macular
      oedema. METHODS: We studied 60 patients with logMAR visual acuity (VA) scores of
      < 0.3 and visual impairment secondary to BRVO-associated macular oedema. All
      patients underwent PPV with arteriovenous sheathotomy. At the time of PPV,
      vitreous samples were collected from the operated eye and vitreous levels of VEGF
      and IL-6 were measured. Best corrected VA (BCVA) (using a logMAR chart) and
      foveal thickness (FT) (using optical coherence tomography) were monitored for up
      to 6 months after PPV. RESULTS: Both BCVA and FT significantly improved after
      PPV. According to multiple regression analysis, both the improvement in BCVA and
      decrease in FT were closely related to the vitreous level of IL-6 but not to that
      of VEGF. The vitreous level of VEGF was strongly correlated with duration of
      BRVO. CONCLUSIONS: Both improvement in BCVA and decrease in FT were observed
      after PPV in BRVO patients with macular oedema. Interestingly, these visual
      prognoses strongly correlate with the vitreous level of IL-6, whereas the
      duration of BRVO strongly correlates with the vitreous level of VEGF.

PMID- 18039347
TI  - Success rates for switching to dorzolamide/timolol fixed combination in timolol
      responders who are insufficiently controlled by latanoprost monotherapy.
AB  - PURPOSE: We aimed to investigate the safety and efficacy of dorzolamide/timolol
      fixed combination (DTFC) in timolol responders with ocular hypertension or open
      angle glaucoma who switched to DTFC because of insufficient control on
      latanoprost. METHODS: We carried out a prospective, open-label cohort study with
      an active-historical control in which qualifying patients must have been treated
      with latanoprost monotherapy for at least 4 weeks, must have demonstrated
      insufficiently controlled intraocular pressure (IOP) (> or = 19 mmHg at 08.00
      hours), and must have shown a decrease in IOP at 2 hours after timolol
      instillation of > or = 3 mmHg or > or = 15%. Patients then began DTFC dosed at
      08.00 hours and 20.00 hours and discontinued latanoprost. Patients were evaluated
      again after 4 and 12 weeks. RESULTS: In 57 patients IOP was further reduced by
      2.4 +/- 3.3 mmHg at 08.00 hours (p < 0.0001) and by 3.5 +/- 3.3 mmHg at 10.00
      hours (p < 0.0001) after switching to DTFC. Responses to the Comparison of
      Ophthalmic Medications for Tolerability (COMTol) questionnaire showed no
      difference between DTFC and latanoprost for in terms of overall preference,
      typical daily activities, limitation of activities, compliance, satisfaction or
      quality of life (p > 0.05). However, greater frequency in burning and/or stinging
      (p < 0.0001) and bitter taste (p < 0.0001) were observed with DTFC, whereas
      unusual taste (p = 0.02) and itchy eyes (p = 0.05) were associated with
      latanoprost. CONCLUSIONS: This study suggests that patients who are
      insufficiently controlled on latanoprost monotherapy, and who are timolol
      responders, can generally achieve further IOP reduction and similar tolerance
      levels when changed to DTFC.

PMID- 18039348
TI  - Accommodative esotropia following surgical treatment of infantile esotropia:
      frequency and risk factors.
AB  - PURPOSE: We aimed to examine the frequency of and risk factors for the
      development of accommodative esotropia following surgical treatment for infantile
      esotropia. METHODS: A total of 29 children were recruited. Potential risk factors
      for the development of accommodative esotropia included: sex; angle of deviation
      at initial and final visits; cycloplegic refractive error at initial and final
      visits; increase in hyperopia; amblyopia; amblyopia treatment; age at surgical
      treatment; pre- and postoperative latent nystagmus; dissociated vertical
      deviation or inferior oblique muscle overaction; additional surgical procedures;
      unstable alignment, and binocular sensory status. RESULTS: Overall, 14 (48.2%) of
      29 children developed accommodative esotropia during the 36- to 132-month
      postoperative follow-up period. Twelve (85.7%) of the 14 patients developed
      refractive accommodative esotropia and two developed non-refractive accommodative
      esotropia. The onset of accommodative esotropia occurred at a mean of 8.8 months
      (range 6-24 months) after the initial surgical alignment. This corresponded to a
      mean age of onset for accommodative esotropia of 43.2 months. We determined that,
      among children with infantile esotropia, those who had hyperopia of > or = 3.0 D
      and increasing hyperopia after surgery and those who did not develop dissociated
      vertical deviation during the follow-up period were more likely to develop
      accommodative esotropia. CONCLUSIONS: Children who have the established risk
      factors should be followed closely for the development of accommodative
      esotropia. The treatment of these children with appropriate glasses may prevent
      the development of adverse effects of accommodative esotropia on sensory and
      motor functions.

PMID- 18039349
TI  - Vogt-Koyanagi-Harada syndrome in a Greenlandic Inuit.
AB  - PURPOSE: To report a case of Vogt-Koyanagi-Harada syndrome (VKH) in an Inuit.
      METHODS: We carried out a medical evaluation and human leucocyte antigen (HLA)
      genotyping. RESULTS: A 36-year-old male Inuit developed severely decreased
      vision, intense headache and vertigo over a 3-week period. Ocular examination
      revealed panuveitis with bilateral serous retinal detachment and optic nerve head
      oedema. There was no history of ocular trauma or evidence suggestive of other
      disease entities. The patient responded well to high-dose systemic prednisolone.
      Vitiligo presented late in the course. CONCLUSIONS: This case report describes
      the first published case of VKH in a patient of Inuit ancestry. The patient was
      homozygous for HLA-DR4, a genotype previously associated with VKH.

PMID- 18039350
TI  - Intraocular pressure in an ophthalmologically normal Japanese population.
AB  - PURPOSE: To investigate the distribution of intraocular pressure (IOP) measured
      by Goldmann applanation tonometry (GAT) and factors correlating with IOP, with
      special attention to age, in a large sample of ophthalmologically normal Japanese
      subjects. METHODS: A total of 7313 subjects (2847 male, 4466 female) were
      selected as a normal Japanese sample. The following exclusion criteria applied:
      abnormal results suggestive of any eye diseases in slit-lamp examination, fundus
      photography or visual field testing using frequency-doubling technology;
      corrected visual acuity < 0.7, and contact lens wear within 1 week of study
      examinations. All subjects were sourced from the Eye Disease Screening Service in
      Tajimi City, which carried out a screening programme between September 2000 and
      October 2001. All data, including subject age, gender, body mass index (BMI),
      systolic blood pressure (BP), laterality, refraction, corneal radius and IOP
      measured with GAT were collected from subject records. Central corneal thickness
      (CCT) was measured by SP-2000P specular microscopy. Levels of IOP and correlating
      factors were statistically analysed. RESULTS: Average IOP was 14.1 +/- 2.3 mmHg
      (mean +/- standard deviation; n = 7313 x 2). Mean IOP levels in male and female
      subjects were 14.1 +/- 2.3 mmHg and 14.1 +/- 2.2 mmHg, respectively. There was no
      difference in IOP between male and female subjects. Multiple regression analysis
      indicated that IOP had negative correlations with age, corneal radius and
      refraction (p < 0.0001), and positive correlations with CCT, systolic BP and BMI
      (p < 0.0001). CONCLUSIONS: In a large-scale population of ophthalmologically
      normal Japanese subjects, IOP measured by GAT was significantly and negatively
      correlated with age. It was also negatively correlated with corneal radius and
      refraction, and positively with CCT, systolic BP and BMI.

PMID- 18039351
TI  - Safety and pharmacokinetics of a recombinant factor VIII with pegylated liposomes
      in severe hemophilia A.
AB  - BACKGROUND: BAY 79-4980 is a sucrose-formulated recombinant factor VIII (rFVIII
      FS) combined with pegylated liposomes to prolong activity. OBJECTIVES: To
      investigate the safety, tolerability, bioavailability, pharmacokinetics and
      pharmacodynamics of a single administration of BAY 79-4980 compared with standard
      rFVIII-FS in patients with severe hemophilia A. METHODS: This randomized, double
      blind study consisted of two crossover substudies comparing two doses of
      liposomal rFVIII-FS with standard rFVIII-FS. Males (12-60 years) with severe
      hemophilia A received a single infusion of standard rFVIII-FS (35 IU kg(-1))
      followed by a single infusion of BAY 79-4980 (13 or 22 mg kg(-1) pegylated
      liposomes) or vice versa, with 12 observation days and a 2-day washout period
      between treatments. RESULTS: Twenty-six subjects were enrolled at two centers. No
      serious adverse events were reported. Transient increases in complement C3a, but
      not CH50, were seen in subjects receiving both the low- and high-liposome-dose
      BAY 79-4980. Mild transient elevations of total and low-density lipoprotein
      cholesterol were observed. There were no clinically significant differences in
      clotting or laboratory parameters or in pharmacokinetic behavior between BAY 79
      4980 and standard rFVIII-FS. The number of subjects with spontaneous bleeds on
      days 1-14 postinfusion was low, and group comparisons were inconclusive.
      CONCLUSIONS: Single-dose administration of BAY 79-4980 is well tolerated in
      patients with severe hemophilia A. Plasma pharmacokinetics of FVIII cannot
      explain the extended protection from bleeding observed previously with BAY 79
      4980. Further studies of efficacy and long-term safety of chronic administration
      are planned.

PMID- 18039354
TI  - Comparative genomic analysis of the odorant-binding protein family in 12
      Drosophila genomes: purifying selection and birth-and-death evolution.
AB  - BACKGROUND: Chemoreception is a widespread mechanism that is involved in critical
      biologic processes, including individual and social behavior. The insect
      peripheral olfactory system comprises three major multigene families: the
      olfactory receptor (Or), the gustatory receptor (Gr), and the odorant-binding
      protein (OBP) families. Members of the latter family establish the first contact
      with the odorants, and thus constitute the first step in the chemosensory
      transduction pathway. RESULTS: Comparative analysis of the OBP family in 12
      Drosophila genomes allowed the identification of 595 genes that encode putative
      functional and nonfunctional members in extant species, with 43 gene gains and 28
      gene losses (15 deletions and 13 pseudogenization events). The evolution of this
      family shows tandem gene duplication events, progressive divergence in DNA and
      amino acid sequence, and prevalence of pseudogenization events in external
      branches of the phylogenetic tree. We observed that the OBP arrangement in
      clusters is maintained across the Drosophila species and that purifying selection
      governs the evolution of the family; nevertheless, OBP genes differ in their
      functional constraints levels. Finally, we detect that the OBP repertoire evolves
      more rapidly in the specialist lineages of the Drosophila melanogaster group (D.
      sechellia and D. erecta) than in their closest generalists. CONCLUSION: Overall,
      the evolution of the OBP multigene family is consistent with the birth-and-death
      model. We also found that members of this family exhibit different functional
      constraints, which is indicative of some functional divergence, and that they
      might be involved in some of the specialization processes that occurred through
      the diversification of the Drosophila genus.

PMID- 18039355
TI  - Complete gene expression profiling of Saccharopolyspora erythraea using GeneChip
      DNA microarrays.
AB  - BACKGROUND: The Saccharopolyspora erythraea genome sequence, recently published,
      presents considerable divergence from those of streptomycetes in gene
      organization and function, confirming the remarkable potential of S. erythraea
      for producing many other secondary metabolites in addition to erythromycin. In
      order to investigate, at whole transcriptome level, how S. erythraea genes are
      modulated, a DNA microarray was specifically designed and constructed on the S.
      erythraea strain NRRL 2338 genome sequence, and the expression profiles of 6494
      ORFs were monitored during growth in complex liquid medium. RESULTS: The
      transcriptional analysis identified a set of 404 genes, whose transcriptional
      signals vary during growth and characterize three distinct phases: a rapid growth
      until 32 h (Phase A); a growth slowdown until 52 h (Phase B); and another rapid
      growth phase from 56 h to 72 h (Phase C) before the cells enter the stationary
      phase. A non-parametric statistical method, that identifies chromosomal regions
      with transcriptional imbalances, determined regional organization of
      transcription along the chromosome, highlighting differences between core and non
      core regions, and strand specific patterns of expression. Microarray data were
      used to characterize the temporal behaviour of major functional classes and of
      all the gene clusters for secondary metabolism. The results confirmed that the
      ery cluster is up-regulated during Phase A and identified six additional clusters
      (for terpenes and non-ribosomal peptides) that are clearly regulated in later
      phases. CONCLUSION: The use of a S. erythraea DNA microarray improved specificity
      and sensitivity of gene expression analysis, allowing a global and at the same
      time detailed picture of how S. erythraea genes are modulated. This work
      underlines the importance of using DNA microarrays, coupled with an exhaustive
      statistical and bioinformatic analysis of the results, to understand the
      transcriptional organization of the chromosomes of micro-organisms producing
      natural products.

PMID- 18039352
TI  - Clathrin-independent internalization and recycling.
AB  - The functionality of receptor and channel proteins depends directly upon their
      expression level on the plasma membrane. Therefore, the ability to selectively
      adjust the surface level of a particular receptor or channel protein is pivotal
      to many cellular signaling events. The internalization and recycling pathway
      plays a major role in the regulation of protein surface level, and thus has been
      a focus of research for many years. Although several endocytic pathways have been
      identified, most of our knowledge has come from the clathrin-dependent pathway,
      while the other pathways remain much less well defined. Considering that clathrin
      independent internalization may account for as much as 50% of the total endocytic
      activity in the cell, the lack of such knowledge constitutes a major gap in our
      efforts to understand how different internalization pathways are utilized and
      coordinated. Recent studies have provided valuable insights into this area, yet
      many more questions still remain. In this review, we will give a panoramic
      introduction to the current knowledge of various internalization and recycling
      pathways, with an emphasis on the latest findings that have broadened our view of
      the clathrin-independent pathways. We will also dedicate one section to the
      emerging studies of the clathrin-independent internalization pathways in neuronal
      cells.

PMID- 18039356
TI  - Semiquantitative RT-PCR measurement of gene expression in rat tissues including a
      correction for varying cell size and number.
AB  - BACKGROUND: Current methodology of gene expression analysis limits the
      possibilities of comparison between cells/tissues of organs in which cell size
      and/or number changes as a consequence of the study (e.g. starvation). A method
      relating the abundance of specific mRNA copies per cell may allow direct
      comparison or different organs and/or changing physiological conditions. METHODS:
      With a number of selected genes, we analysed the relationship of the number of
      bases and the fluorescence recorded at a present level using cDNA standards. A
      lineal relationship was found between the final number of bases and the length of
      the transcript. The constants of this equation and those of the relationship
      between fluorescence and number of bases in cDNA were determined and a general
      equation linking the length of the transcript and the initial number of copies of
      mRNA was deduced for a given pre-established fluorescence setting. This allowed
      the calculation of the concentration of the corresponding mRNAs per g of tissue.
      The inclusion of tissue RNA and the DNA content per cell, allowed the calculation
      of the mRNA copies per cell. RESULTS: The application of this procedure to six
      genes: Arbp, cyclophilin, ChREBP, T4 deiodinase 2, acetyl-CoA carboxylase 1 and
      IRS-1, in liver and retroperitoneal adipose tissue of food-restricted rats
      allowed precise measures of their changes irrespective of the shrinking of the
      tissue, the loss of cells or changes in cell size, factors that deeply complicate
      the comparison between changing tissue conditions. The percentage results
      obtained with the present methods were essentially the same obtained with the
      delta-delta procedure and with individual cDNA standard curve quantitative RT-PCR
      estimation. CONCLUSION: The method presented allows the comparison (i.e. as
      copies of mRNA per cell) between different genes and tissues, establishing the
      degree of abundance of the different molecular species tested.

PMID- 18039357
TI  - Mechanical properties during healing of Achilles tendon ruptures to predict final
      outcome: a pilot Roentgen stereophotogrammetric analysis in 10 patients.
AB  - BACKGROUND: There are presently few methods described for in vivo monitoring of
      the mechanics of healing human tendon ruptures, and no methods for prediction of
      clinical outcome. We tested if Roentgen stereophotogrammetric analysis (RSA) can
      be used to follow the restoration of mechanical properties during healing of
      ruptured Achilles tendons, and if early measurements can predict clinical
      results. METHODS: Achilles tendon repair was studied with RSA in 10 patients with
      a total rupture. Tantalum beads were implanted in conjunction with surgical
      repair. The patients were evaluated at 6, 12 and 18 weeks, and after 1 year. RSA
      was performed with two different mechanical loadings, and the strain induced by
      increasing load was measured. The transverse area was determined by ultrasound.
      CT scan at 12 weeks confirmed that the tantalum beads were located within the
      tendons. Functional testing was done after 1 year. A heel raise index was chosen
      as primary clinical outcome variable. RESULTS: The strain was median 0.90, 0.32
      and 0.14 percent per 100 N tendon force at 6 weeks, 18 weeks and one year
      respectively. The error of measurement was 0.04 percent units at 18 weeks. There
      was a large variation between patients, which appears to reflect biological
      variation. From 6 to 18 weeks, there was a negative correlation between increase
      in transverse area and increase in material properties, suggesting that healing
      is regulated at the organ level, to maximize stiffness. Modulus of elasticity
      during this time correlated with a heel raise index at one year (Rho = 0.76; p =
      0.02). CONCLUSION: We conclude that the RSA method might have potential for
      comparing different treatments of Achilles tendon ruptures.

PMID- 18039358
TI  - Serendipitous diagnosis of aortic coarctation by bilateral parvus et tardus renal
      Doppler flow pattern.
AB  - BACKGROUND: Aorta Coarctation (AC) is uncommon condition that in most adult
      patients is asymptomatic. Diagnosis of AC is made during routine physical
      examination by detection of Blood Pressure (BP) difference between arm and leg.
      AIM: To describe a novel renal artery Doppler flow pattern pathognomonic of
      aortic coarctation. METHODS: We enrolled 4 consecutive patients referred to renal
      artery Doppler Ultrasonography (DU) for diagnostic work-up of secondary arterial
      hypertension. All met the following inclusion criteria: 1) arterial hypertension
      at age <30 years; 2) referred for renal DU to rule out renovascular hypertension.
      RESULTS: We found in all 4 patients (age range 10 to 27 years) a bilateral
      "parvus-tardus" renal Doppler flow pattern. In all, echocardiographic and
      angiographic work-ups showed aortic coarctation. CONCLUSION: Careful physical
      examination should be performed in all hypertensive patients. Furthermore, the
      suspicion of AC can be raised by a bilateral renal arteries "parvus-tardus"
      Doppler flow pattern in young hypertensive patients screened for secondary
      hypertension.

PMID- 18039359
TI  - Anterior chest wall tuberculous abscess: a case report.
AB  - The granulomatous inflammation of tuberculosis usually involves the lungs and
      the hilar lymph nodes. Musculoskeletal tuberculosis (TB) occurs in 1-3% of
      patients with TB, while TB of the chest wall constitutes 1% to 5% of all cases of
      musculoskeletal TB. Furthermore, nowadays it is rarer to find extrapulmonary TB
      in immunocompetent rather that non-immunocompetent patients. The present case
      reports a fifty-six-year-old immunocompetent man with an anterior chest wall
      tuberculous abscess. The rarity of the present case relates both to the
      localization of the tuberculous abscess, and to the fact that the patient was
      immunocompetent. The diagnosis of musculoskeletal tuberculous infection remains a
      challenge for clinicians and requires a high index of suspicion. The combination
      of indolent onset of symptoms, positive tuberculin skin test, and compatible
      radiographic findings, strongly suggests the diagnosis. TB, however, must be
      confirmed by positive culture or histologic proof. Prompt diagnosis and treatment
      are important to prevent serious bone and joint destruction.

PMID- 18039360
TI  - Hannover study on long-stay hospitalization - part II: Characteristics and care
      conditions of long-stay hospitalization in cases of chronic mental illness.
AB  - BACKGROUND: Long-stay hospitalization is often a consequence of insufficient care
      structures. This article examines the characteristics and care conditions of long
      stay hospitalization (LSH) in an urban area in Germany. METHODS: Extensive data
      of patients in the urban catchment area of the Medical School of Hannover,
      capital of Lower Saxony, were evaluated during a 10 years period. RESULTS AND
      CONCLUSION: Community psychiatric efforts certainly help to reduce long-stay
      hospitalization, but cannot fully prevent it. Reference figures are given for
      comparable urbanized areas: consequently 500 chronically mentally ill persons per
      100.000 inhabitants must be expected, 20% of which must be considered as long
      stay hospitalized according to a given definition. We estimate 250 places per
      100.000 inhabitants to be required for institutionalised outpatient care, further
      30 places for day clinic and full-time in-patient treatment and 40 places for
      residential home treatment. We suggest these results as a guidance for
      psychiatric planning in comparable communities.

PMID- 18039362
TI  - Looking inside the black box: a theory-based process evaluation alongside a
      randomised controlled trial of printed educational materials (the Ontario printed
      educational message, OPEM) to improve referral and prescribing practices in
      primary care in Ontario, Canada.
AB  - BACKGROUND: Randomised controlled trials of implementation strategies tell us
      whether (or not) an intervention results in changes in professional behaviour but
      little about the causal mechanisms that produce any change. Theory-based process
      evaluations collect data on theoretical constructs alongside randomised trials to
      explore possible causal mechanisms and effect modifiers. This is similar to
      measuring intermediate endpoints in clinical trials to further understand the
      biological basis of any observed effects (for example, measuring lipid profiles
      alongside trials of lipid lowering drugs where the primary endpoint could be
      reduction in vascular related deaths).This study protocol describes a theory
      based process evaluation alongside the Ontario Printed Educational Message (OPEM)
      trial. We hypothesize that the OPEM interventions are most likely to operate
      through changes in physicians' behavioural intentions due to improved attitudes
      or subjective norms with little or no change in perceived behavioural control. We
      will test this hypothesis using a well-validated social cognition model, the
      theory of planned behaviour (TPB) that incorporates these constructs.
      METHODS/DESIGN: We will develop theory-based surveys using standard methods based
      upon the TPB for the second and third replications, and survey a subsample of
      Ontario family physicians from each arm of the trial two months before and six
      months after the dissemination of the index edition of informed, the evidence
      based newsletter used for the interventions. In the third replication, our study
      will converge with the "TRY-ME" protocol (a second study conducted alongside the
      OPEM trial), in which the content of educational messages was constructed using
      both standard methods and methods informed by psychological theory. We will
      modify Dillman's total design method to maximise response rates. Preliminary
      analyses will initially assess the internal reliability of the measures and use
      regression to explore the relationships between predictor and dependent variable
      (intention to advise diabetic patients to have annual retinopathy screening and
      to prescribe thiazide diuretics for first line treatment of uncomplicated
      hypertension). We will then compare groups using methods appropriate for
      comparing independent samples to determine whether there have been changes in the
      predicted constructs (attitudes, subjective norms, or intentions) across the
      study groups as hypothesised, and will assess the convergence between the process
      evaluation results and the main trial results.

PMID- 18039361
TI  - The Ontario printed educational message (OPEM) trial to narrow the evidence
      practice gap with respect to prescribing practices of general and family
      physicians: a cluster randomized controlled trial, targeting the care of
      individuals with diabetes and hypertension in Ontario, Canada.
AB  - BACKGROUND: There are gaps between what family practitioners do in clinical
      practice and the evidence-based ideal. The most commonly used strategy to narrow
      these gaps is the printed educational message (PEM); however, the attributes of
      successful printed educational messages and their overall effectiveness in
      changing physician practice are not clear. The current endeavor aims to determine
      whether such messages change prescribing quality in primary care practice, and
      whether these effects differ with the format of the message. METHODS/DESIGN: The
      design is a large, simple, factorial, unblinded cluster-randomized controlled
      trial. PEMs will be distributed with informed, a quarterly evidence-based
      synopsis of current clinical information produced by the Institute for Clinical
      Evaluative Sciences, Toronto, Canada, and will be sent to all eligible general
      and family practitioners in Ontario. There will be three replicates of the trial,
      with three different educational messages, each aimed at narrowing a specific
      evidence-practice gap as follows: 1) angiotensin-converting enzyme inhibitors,
      hypertension treatment, and cholesterol lowering agents for diabetes; 2) retinal
      screening for diabetes; and 3) diuretics for hypertension.For each of the three
      replicates there will be three intervention groups. The first group will receive
      informed with an attached postcard-sized, short, directive "outsert." The second
      intervention group will receive informed with a two-page explanatory "insert" on
      the same topic. The third intervention group will receive informed, with both the
      above-mentioned outsert and insert. The control group will receive informed only,
      without either an outsert or insert.Routinely collected physician billing,
      prescription, and hospital data found in Ontario's administrative databases will
      be used to monitor pre-defined prescribing changes relevant and specific to each
      replicate, following delivery of the educational messages. Multi-level modeling
      will be used to study patterns in physician-prescribing quality over four
      quarters, before and after each of the three interventions. Subgroup analyses
      will be performed to assess the association between the characteristics of the
      physician's place of practice and target behaviours.A further analysis of the
      immediate and delayed impacts of the PEMs will be performed using time-series
      analysis and interventional, auto-regressive, integrated moving average modeling.

PMID- 18039363
TI  - Testing a TheoRY-inspired MEssage ('TRY-ME'): a sub-trial within the Ontario
      Printed Educational Message (OPEM) trial.
AB  - BACKGROUND: A challenge for implementation researchers is to develop principles
      that could generate testable hypotheses that apply across a range of clinical
      contexts, thus leading to generalisability of findings. Such principles may be
      provided by systematically developed theories. The opportunity has arisen to test
      some of these theoretical principles in the Ontario Printed Educational Materials
      (OPEM) trial by conducting a sub-trial within the existing trial structure. OPEM
      is a large factorial cluster-randomised trial evaluating the effects of short
      directive and long discursive educational messages embedded into informed, an
      evidence-based newsletter produced in Canada by the Institute for Clinical
      Evaluative Sciences (ICES) and mailed to all primary care physicians in Ontario.
      The content of educational messages in the sub-trial will be constructed using
      both standard methods and methods inspired by psychological theory. The aim of
      this study is to test the effectiveness of the TheoRY-inspired MEssage ('TRY-ME')
      compared with the 'standard' message in changing prescribing behaviour. METHODS:
      The OPEM trial participants randomised to receive the short directive message
      attached to the outside of informed (an 'outsert') will be sub-randomised to
      receive either a standard message or a message informed by the theory of planned
      behaviour (TPB) using a two (long insert or no insert) by three (theory-based
      outsert or standard outsert or no outsert) design. The messages will relate to
      prescription of thiazide diuretics as first line drug treatment for hypertension
      (described in the accompanying protocol, "The Ontario Printed Educational
      Materials trial"). The short messages will be developed independently by two
      research teams.The primary outcome is prescription of thiazide diuretics,
      measured by routinely collected data available within ICES. The study is designed
      to answer the question, is there any difference in guideline adherence (i.e.,
      thiazide prescription rates) between physicians in the six groups? A process
      evaluation survey instrument based on the TPB will be administered pre- and post
      intervention (described in the accompanying protocol, "Looking inside the black
      box"). The second research question concerns processes that may underlie observed
      differences in prescribing behaviour. We expect that effects of the messages on
      prescribing behaviour will be mediated through changes in physicians' cognitions.

PMID- 18039364
TI  - OMERACT: an international initiative to improve outcome measurement in
      rheumatology.
AB  - OMERACT is the acronym for an international, informally organized network
      initiated in 1992 aimed at improving outcome measurement in rheumatology. Chaired
      by an executive committee, it organizes consensus conferences in a 2-yearly cycle
      that circles the globe. Data driven recommendations are prepared and updated by
      expert working groups. Recommendations include core sets of measures for most of
      the major rheumatologic conditions. Since 2002 patients have been actively
      engaged in the process.

PMID- 18039365
TI  - Standardising outcomes for clinical trials and systematic reviews.

PMID- 18039366
TI  - Differential gene expression profile in pig adipose tissue treated with/without
      clenbuterol.
AB  - BACKGROUND: Clenbuterol, a beta-agonist, can dramatically reduce pig adipose
      accumulation at high dosages. However, it has been banned in pig production
      because people who eat pig products treated with clenbuterol can be poisoned by
      the clenbuterol residues. To understand the molecular mechanism for this fat
      reduction, cDNA microarray, real-time PCR, two-dimensional electrophoresis and
      mass spectra were used to study the differential gene expression profiles of pig
      adipose tissues treated with/without clenbuterol. The objective of this research
      is to identify novel genes and physiological pathways that potentially facilitate
      clenbuterol induced reduction of adipose accumulation. RESULTS: Clenbuterol was
      found to improve the lean meat percentage about 10 percent (P < 0.05). The
      adipose cells became smaller and the muscle fibers became thicker with the
      administration of clenbuterol. The mRNA abundance levels of 82 genes (ESTs) were
      found to be statistically differentially expressed based on the Student t-test (P
      < 0.05) in the microarray analyses which contained 3358 genes (ESTs). These 82
      genes (ESTs) were divided into four groups according to their Gene Ontology
      Biological Process descriptions. 16 genes were cellular metabolism related genes
      (including five related to lipid metabolism such as apolipoprotein D and
      apolipoprotein R), 10 were signal transduction related genes, 45 were expressed
      sequence tags (ESTs) and 11 others were of various categories. Eleven of the 82
      genes (ESTs) were chosen for real-time PCR analysis, with eight genes showing
      similar induction magnitude as that seen in the microarray data. Apolipoprotein R
      was also found to be up-regulated by the proteomic analysis. CONCLUSION: Pig fat
      accumulation was reduced dramatically with clenbuterol treatment. Histological
      sections and global evaluation of gene expression after administration of
      clenbuterol in pigs identified profound changes in adipose cells. With
      clenbuterol stimulation, adipose cell volumes decreased and their gene expression
      profile changed, which indicate some metabolism processes have been also altered.
      Although the biological functions of the differentially expressed genes are not
      completely known, higher expressions of these molecules in adipose tissue might
      contribute to the reduction of fat accumulation. Among these genes, five lipid
      metabolism related genes were of special interest for further study, including
      apoD and apoR. The apoR expression was increased at both the RNA and protein
      levels. The apoR may be one of the critical molecules through which clenbuterol
      reduces fat accumulation.

PMID- 18039367
TI  - Years of sunlight exposure and cataract: a case-control study in a Mediterranean
      population.
AB  - BACKGROUND: We aimed to investigate the relation between sunlight exposure and
      risk of cataract. METHODS: We carried out a frequency-matched case-control study
      of 343 cases and 334 controls attending an ophthalmology outpatient clinic at a
      primary health-care center in a small town near Valencia, Spain. All cases were
      diagnosed as having a cataract in at least one eye based on the Lens
      Opacification Classification system (LOCS II). Controls had no opacities in
      either eye. All cases and controls were interviewed for information on outdoor
      exposure, "usual" diet, history of severe episodes of diarrhea illness, life
      style factors and medical and socio-demographic variables. Blood antioxidant
      vitamin levels were also analyzed. We used logistic regression models to estimate
      sex and age-adjusted odds ratios (ORs) by quintiles of years of occupational
      outdoor exposure, adjusting for potential confounders such as smoking, alcohol
      consumption, serum antioxidants and education. RESULTS: No association was found
      between years of outdoor exposure and risk of cataract. However, exploratory
      analyses suggested a positive association between years of outdoor exposure at
      younger ages and risk of nuclear cataract later in life. CONCLUSION: Our study
      does not support an association with cataract and sunlight exposure over adult
      life.

PMID- 18039368
TI  - Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional
      study.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with
      bronchial epithelial changes, including squamous cell metaplasia and goblet cell
      hyperplasia. These features are partially attributed to activation of the
      epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces
      respiratory symptoms and lung function decline in COPD, inflammation persists. We
      determined epithelial proliferation and composition in bronchial biopsies from
      current and ex-smokers with COPD, and its relation to duration of smoking
      cessation. METHODS: 114 COPD patients were studied cross-sectionally: 99 males/15
      females, age 62 +/- 8 years, median 42 pack-years, no corticosteroids, current (n
      = 72) or ex-smokers (n = 42, median cessation duration 3.5 years),
      postbronchodilator FEV1 63 +/- 9% predicted. Squamous cell metaplasia (%), goblet
      cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm
      basement membrane), and EGFR expression (%) were measured in intact epithelium of
      bronchial biopsies. RESULTS: Ex-smokers with COPD had significantly less
      epithelial squamous cell metaplasia, proliferating cell numbers, and a trend
      towards reduced goblet cell area than current smokers with COPD (p = 0.025, p =
      0.001, p = 0.081, respectively), but no significant difference in EGFR
      expression. Epithelial features were not different between short-term quitters
      (<3.5 years) and current smokers. Long-term quitters (> or =3.5 years) had less
      goblet cell area than both current smokers and short-term quitters (medians: 7.9%
      vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less
      proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).
      CONCLUSION: Ex-smokers with COPD had less bronchial epithelial remodelling than
      current smokers, which was only observed after long-term smoking cessation (>3.5
      years). TRIAL REGISTRATION: NCT00158847.

PMID- 18039369
TI  - PHOSIDA (phosphorylation site database): management, structural and evolutionary
      investigation, and prediction of phosphosites.
AB  - PHOSIDA http://www.phosida.com, a phosphorylation site database, integrates
      thousands of high-confidence in vivo phosphosites identified by mass spectrometry
      based proteomics in various species. For each phosphosite, PHOSIDA lists matching
      kinase motifs, predicted secondary structures, conservation patterns, and its
      dynamic regulation upon stimulus. Using support vector machines, PHOSIDA also
      predicts phosphosites.

PMID- 18039370
TI  - In situ analysis of cross-hybridisation on microarrays and the inference of
      expression correlation.
AB  - BACKGROUND: Microarray co-expression signatures are an important tool for
      studying gene function and relations between genes. In addition to genuine
      biological co-expression, correlated signals can result from technical
      deficiencies like hybridization of reporters with off-target transcripts. An
      approach that is able to distinguish these factors permits the detection of more
      biologically relevant co-expression signatures. RESULTS: We demonstrate a
      positive relation between off-target reporter alignment strength and expression
      correlation in data from oligonucleotide genechips. Furthermore, we describe a
      method that allows the identification, from their expression data, of individual
      probe sets affected by off-target hybridization. CONCLUSION: The effects of off
      target hybridization on expression correlation coefficients can be substantial,
      and can be alleviated by more accurate mapping between microarray reporters and
      the target transcriptome. We recommend attention to the mapping for any
      microarray analysis of gene expression patterns.

PMID- 18039371
TI  - Dynacortin facilitates polarization of chemotaxing cells.
AB  - BACKGROUND: Cell shape changes during cytokinesis and chemotaxis require
      regulation of the actin cytoskeletal network. Dynacortin, an actin cross-linking
      protein, localizes to the cell cortex and contributes to cortical resistance,
      thereby helping to define the cell shape changes of cytokinesis. Dynacortin also
      becomes highly enriched in cortical protrusions, which are sites of new actin
      assembly. RESULTS: We studied the effect of dynacortin on cell motility during
      chemotaxis and on actin dynamics in vivo and in vitro. Dynacortin enriches with
      the actin, particularly at the leading edge of chemotaxing cells. Cells devoid of
      dynacortin do not become as polarized as wild-type control cells but move with
      similar velocities as wild-type cells. In particular, they send out multiple
      pseudopods that radiate at a broader distribution of angles relative to the
      chemoattractant gradient. Wild-type cells typically only send out one pseudopod
      at a time that does not diverge much from 0 degrees on average relative to the
      gradient. Though dynacortin-deficient cells show normal bulk (whole-cell) actin
      assembly upon chemoattractant stimulation, dynacortin can promote actin assembly
      in vitro. By fluorescence spectroscopy, co-sedimentation and transmission
      electron microscopy, dynacortin acts as an actin scaffolder in which it assembles
      actin monomers into polymers with a stoichiometry of 1 Dyn2:1 actin under salt
      conditions that disfavor polymer assembly. CONCLUSION: Dynacortin contributes to
      cell polarization during chemotaxis. By cross-linking and possibly stabilizing
      actin polymers, dynacortin also contributes to cortical viscoelasticity, which
      may be critical for establishing cell polarity. Though not essential for
      directional sensing or motility, dynacortin is required to establish cell
      polarity, the third core feature of chemotaxis.

PMID- 18039372
TI  - The TriTryp phosphatome: analysis of the protein phosphatase catalytic domains.
AB  - BACKGROUND: The genomes of the three parasitic protozoa Trypanosoma cruzi,
      Trypanosoma brucei and Leishmania major are the main subject of this study. These
      parasites are responsible for devastating human diseases known as Chagas disease,
      African sleeping sickness and cutaneous Leishmaniasis, respectively, that affect
      millions of people in the developing world. The prevalence of these neglected
      diseases results from a combination of poverty, inadequate prevention and
      difficult treatment. Protein phosphorylation is an important mechanism of
      controlling the development of these kinetoplastids. With the aim to further our
      knowledge of the biology of these organisms we present a characterisation of the
      phosphatase complement (phosphatome) of the three parasites. RESULTS: An ontology
      based scan of the three genomes was used to identify 86 phosphatase catalytic
      domains in T. cruzi, 78 in T. brucei, and 88 in L. major. We found interesting
      differences with other eukaryotic genomes, such as the low proportion of tyrosine
      phosphatases and the expansion of the serine/threonine phosphatase family.
      Additionally, a large number of atypical protein phosphatases were identified in
      these species, representing more than one third of the total phosphatase
      complement. Most of the atypical phosphatases belong to the dual-specificity
      phosphatase (DSP) family and show considerable divergence from classic DSPs in
      both the domain organisation and sequence features. CONCLUSION: The analysis of
      the phosphatome of the three kinetoplastids indicates that they possess
      orthologues to many of the phosphatases reported in other eukaryotes, including
      humans. However, novel domain architectures and unusual combinations of accessory
      domains, suggest distinct functional roles for several of the kinetoplastid
      phosphatases, which await further experimental exploration. These distinct traits
      may be exploited in the selection of suitable new targets for drug development to
      prevent transmission and spread of the diseases, taking advantage of the already
      extensive knowledge on protein phosphatase inhibitors.

PMID- 18039373
TI  - Improved protocols for functional analysis in the pathogenic fungus Aspergillus
      flavus.
AB  - BACKGROUND: An available whole genome sequence for Aspergillus flavus provides
      the opportunity to characterize factors involved in pathogenicity and to
      elucidate the regulatory networks involved in aflatoxin biosynthesis. Functional
      analysis of genes within the genome is greatly facilitated by the ability to
      disrupt or mis-express target genes and then evaluate their result on the
      phenotype of the fungus. Large-scale functional analysis requires an efficient
      genetic transformation system and the ability to readily select transformants
      with altered expression, and usually requires generation of double (or multi)
      gene deletion strains or the use of prototrophic strains. However, dominant
      selectable markers, an efficient transformation system and an efficient screening
      system for transformants in A. flavus are absent. RESULTS: The efficiency of the
      genetic transformation system for A. flavus based on uracil auxotrophy was
      improved. In addition, A. flavus was shown to be sensitive to the antibiotic,
      phleomycin. Transformation of A. flavus with the ble gene for resistance to
      phleomycin resulted in stable transformants when selected on 100 mug/ml
      phleomycin. We also compared the phleomycin system with one based on
      complementation for uracil auxotrophy which was confirmed by uracil and 5
      fluoroorotic acid selection and via transformation with the pyr4 gene from
      Neurospora crassa and pyrG gene from A. nidulans in A. flavus NRRL 3357. A
      transformation protocol using pyr4 as a selectable marker resulted in site
      specific disruption of a target gene. A rapid and convenient colony PCR method
      for screening genetically altered transformants was also developed in this study.
      CONCLUSION: We employed phleomycin resistance as a new positive selectable marker
      for genetic transformation of A. flavus. The experiments outlined herein
      constitute the first report of the use of the antibiotic phleomycin for
      transformation of A. flavus. Further, we demonstrated that this transformation
      protocol could be used for directed gene disruption in A. flavus. The
      significance of this is twofold. First, it allows strains to be transformed
      without having to generate an auxotrophic mutation, which is time consuming and
      may result in undesirable mutations. Second, this protocol allows for double gene
      knockouts when used in conjunction with existing strains with auxotrophic
      mutations. To further facilitate functional analysis in this strain we developed
      a colony PCR-based method that is a rapid and convenient method for screening
      genetically altered transformants. This work will be of interest to those working
      on molecular biology of aflatoxin metabolism in A. flavus, especially for
      functional analysis using gene deletion and gene expression.

PMID- 18039375
TI  - Dynamic simulation of regulatory networks using SQUAD.
AB  - BACKGROUND: The ambition of most molecular biologists is the understanding of the
      intricate network of molecular interactions that control biological systems. As
      scientists uncover the components and the connectivity of these networks, it
      becomes possible to study their dynamical behavior as a whole and discover what
      is the specific role of each of their components. Since the behavior of a network
      is by no means intuitive, it becomes necessary to use computational models to
      understand its behavior and to be able to make predictions about it.
      Unfortunately, most current computational models describe small networks due to
      the scarcity of kinetic data available. To overcome this problem, we previously
      published a methodology to convert a signaling network into a dynamical system,
      even in the total absence of kinetic information. In this paper we present a
      software implementation of such methodology. RESULTS: We developed SQUAD, a
      software for the dynamic simulation of signaling networks using the standardized
      qualitative dynamical systems approach. SQUAD converts the network into a
      discrete dynamical system, and it uses a binary decision diagram algorithm to
      identify all the steady states of the system. Then, the software creates a
      continuous dynamical system and localizes its steady states which are located
      near the steady states of the discrete system. The software permits to make
      simulations on the continuous system, allowing for the modification of several
      parameters. Importantly, SQUAD includes a framework for perturbing networks in a
      manner similar to what is performed in experimental laboratory protocols, for
      example by activating receptors or knocking out molecular components. Using this
      software we have been able to successfully reproduce the behavior of the
      regulatory network implicated in T-helper cell differentiation. CONCLUSION: The
      simulation of regulatory networks aims at predicting the behavior of a whole
      system when subject to stimuli, such as drugs, or determine the role of specific
      components within the network. The predictions can then be used to interpret
      and/or drive laboratory experiments. SQUAD provides a user-friendly graphical
      interface, accessible to both computational and experimental biologists for the
      fast qualitative simulation of large regulatory networks for which kinetic data
      is not necessarily available.

PMID- 18039377
TI  - Effects of creatine loading on electromyographic fatigue threshold during cycle
      ergometry in college-aged women.
AB  - The purpose of this study was to examine the effects of 5 days of Creatine (Cr)
      loading on the electromyographic fatigue threshold (EMGFT) in college-aged women.
      Fifteen healthy college-aged women (mean +/- SD = 22.3 +/- 1.7 yrs) volunteered
      to participate in this double-blind, placebo-controlled study and were randomly
      placed into either placebo (PL - 10 g of flavored dextrose powder; n = 8) or
      creatine (Cr - 5 g di-creatine citrate plus 10 g of flavored dextrose powder; n =
      7; Creatine Edge, FSI Nutrition) loading groups. Each group ingested one packet 4
      times per day (total of 20 g/day) for 5 days. Prior to and following
      supplementation, each subject performed a discontinuous incremental cycle
      ergometer test to determine their EMGFT value, using bipolar surface electrodes
      placed on the longitudinal axis of the right vastus lateralis. Subjects completed
      a total of four, 60 second work bouts (ranging from 100-350 W). The EMG amplitude
      was averaged over 10 second intervals and plotted over the 60 second work bout.
      The resulting slopes from each successive work bouts were used to calculate
      EMGFT. A two-way ANOVA (group [Cr vs. PL] x time [pre vs. post]) resulted in a
      significant (p = 0.031) interaction. Furthermore, a dependent samples t-test
      showed a 14.5% +/- 3.5% increase in EMGFT from pre- to post-supplementation with
      Cr (p = 0.009), but no change for the PL treatment (-2.2 +/- 5.8%; p = 0.732). In
      addition, a significant increase (1.0 +/- 0.34 kg; p = 0.049) in weight (kg) was
      observed in the Cr group but no change for PL (-0.2 kg +/- 0.2 kg). These
      findings suggest that 5 days of Cr loading in women may be an effective strategy
      for delaying the onset of neuromuscular fatigue during cycle ergometry.

PMID- 18039376
TI  - Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and
      virus replication in macrophages.
AB  - BACKGROUND: HIV-1 Vpr is a dynamic protein that primarily localizes in the
      nucleus, but a significant fraction is concentrated at the nuclear envelope (NE),
      supporting an interaction between Vpr and components of the nuclear pore complex,
      including the nucleoporin hCG1. In the present study, we have explored the
      contribution of Vpr accumulation at the NE to the Vpr functions, including G2
      arrest and pro-apoptotic activities, and virus replication in primary
      macrophages. RESULTS: In order to define the functional role of Vpr localization
      at the NE, we have characterized a set of single-point Vpr mutants, and selected
      two new mutants with substitutions within the first alpha-helix of the protein,
      Vpr-L23F and Vpr-K27M, that failed to associate with hCG1, but were still able to
      interact with other known relevant host partners of Vpr. In mammalian cells,
      these mutants failed to localize at the NE resulting in a diffuse
      nucleocytoplasmic distribution both in HeLa cells and in primary human monocyte
      derived macrophages. Other mutants with substitutions in the first alpha-helix
      (Vpr-A30L and Vpr-F34I) were similarly distributed between the nucleus and
      cytoplasm, demonstrating that this helix contains the determinants required for
      localization of Vpr at the NE. All these mutations also impaired the Vpr-mediated
      G2-arrest of the cell cycle and the subsequent cell death induction, indicating a
      functional link between these activities and the Vpr accumulation at the NE.
      However, this localization is not sufficient, since mutations within the C
      terminal basic region of Vpr (Vpr-R80A and Vpr-R90K), disrupted the G2-arrest and
      apoptotic activities without altering NE localization. Finally, the replication
      of the Vpr-L23F and Vpr-K27M hCG1-binding deficient mutant viruses was also
      affected in primary macrophages from some but not all donors. CONCLUSION: These
      results indicate that the targeting of Vpr to the nuclear pore complex may
      constitute an early step toward Vpr-induced G2-arrest and subsequent apoptosis;
      they also suggest that Vpr targeting to the nuclear pore complex is not
      absolutely required, but can improve HIV-1 replication in macrophages.

PMID- 18039374
TI  - SOSORT consensus paper: school screening for scoliosis. Where are we today?
AB  - This report is the SOSORT Consensus Paper on School Screening for Scoliosis
      discussed at the 4th International Conference on Conservative Management of
      Spinal Deformities, presented by SOSORT, on May 2007. The objectives were
      numerous, 1) the inclusion of the existing information on the issue, 2) the
      analysis and discussion of the responses by the meeting attendees to the twenty
      six questions of the questionnaire, 3) the impact of screening on frequency of
      surgical treatment and of its discontinuation, 4) the reasons why these programs
      must be continued, 5) the evolving aim of School Screening for Scoliosis and 6)
      recommendations for improvement of the procedure.

PMID- 18039378
TI  - Bronchial epithelial spheroids: an alternative culture model to investigate
      epithelium inflammation-mediated COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
      abnormal lung inflammation that exceeds the protective response. Various culture
      models using epithelial cell lines or primary cells have been used to investigate
      the contribution of bronchial epithelium in the exaggerated inflammation of COPD.
      However, these models do not mimic in vivo situations for several reasons (e.g,
      transformed epithelial cells, protease-mediated dissociation of primary cells,
      etc.). To circumvent these concerns, we developed a new epithelial cell culture
      model. METHODS: Using non transformed non dissociated bronchial epithelium
      obtained by bronchial brushings from COPD and non-COPD smokers, we developed a 3
      dimensional culture model, bronchial epithelial spheroids (BES). BES were
      analyzed by videomicroscopy, light microscopy, immunofluorescence, and
      transmission electron microscopy. We also compared the inflammatory responses of
      COPD and non-COPD BES. In our study, we chose to stimulate BES with
      lipopolycaccharide (LPS) and measured the release of the pro-inflammatory
      mediators interleukin-8 (IL-8) and leukotriene B4 (LTB4) and the anti
      inflammatory mediator prostaglandin E2 (PGE2). RESULTS: BES obtained from both
      COPD and non-COPD patients were characterized by a polarized bronchial epithelium
      with tight junctions and ciliary beating, composed of basal cells, secretory
      cells and ciliated cells. The ciliary beat frequency of ciliated cells was not
      significantly different between the two groups. Of interest, BES retained their
      characteristic features in culture up to 8 days. BES released the inflammatory
      mediators IL-8, PGE2 and LTB4 constitutively and following exposure to LPS.
      Interestingly, LPS induced a higher release of IL-8, but not PGE2 and LTB4 in
      COPD BES (p < 0.001) which correlated with lung function changes. CONCLUSION:
      This study provides for the first time a compelling evidence that the BES model
      provides an unaltered bronchial surface epithelium. More importantly, BES
      represent an attractive culture model to investigate the mechanisms of injuring
      agents that mediate epithelial cell inflammation and its contribution to COPD
      pathogenesis.

PMID- 18039379
TI  - NFU-Enabled FASTA: moving bioinformatics applications onto wide area networks.
AB  - BACKGROUND: Advances in Internet technologies have allowed life science
      researchers to reach beyond the lab-centric research paradigm to create
      distributed collaborations. Of the existing technologies that support distributed
      collaborations, there are currently none that simultaneously support data storage
      and computation as a shared network resource, enabling computational burden to be
      wholly removed from participating clients. Software using computation-enable
      logistical networking components of the Internet Backplane Protocol provides a
      suitable means to accomplish these tasks. Here, we demonstrate software that
      enables this approach by distributing both the FASTA algorithm and appropriate
      data sets within the framework of a wide area network. RESULTS: For large
      datasets, computation-enabled logistical networks provide a significant reduction
      in FASTA algorithm running time over local and non-distributed logistical
      networking frameworks. We also find that genome-scale sizes of the stored data
      are easily adaptable to logistical networks. CONCLUSION: Network function unit
      enabled Internet Backplane Protocol effectively distributes FASTA algorithm
      computation over large data sets stored within the scaleable network. In
      situations where computation is subject to parallel solution over very large data
      sets, this approach provides a means to allow distributed collaborators access to
      a shared storage resource capable of storing the large volumes of data equated
      with modern life science. In addition, it provides a computation framework that
      removes the burden of computation from the client and places it within the
      network.

PMID- 18039380
TI  - Stability and assembly in vitro of bacteriophage PP7 virus-like particles.
AB  - BACKGROUND: The stability of a virus-like particle (VLP) is an important
      consideration for its use in nanobiotechnology. The icosahedral capsid of the RNA
      bacteriophage PP7 is cross-linked by disulfide bonds between coat protein dimers
      at its 5-fold and quasi-6-fold symmetry axes. This work determined the effects of
      these disulfides on the VLP's thermal stability. RESULTS: Measurements of the
      thermal denaturation behavior of PP7 VLPs in the presence and absence of a
      reducing agent show that disulfide cross-links substantially stabilize them
      against thermal denaturation. Although dimers in the capsid are linked to one
      another by disulfides, the two subunits of dimers themselves are held together
      only by non-covalent interactions. In an effort to confer even greater stability
      a new cross-link was introduced by genetically fusing two coat protein monomers,
      thus producing a "single-chain dimer" that assembles normally into a completely
      cross-linked VLP. However, subunit fusion failed to increase the thermal
      stability of the particles, even though it stabilized the isolated dimer. As a
      step toward gaining control of the internal composition of the capsid, conditions
      that promote the assembly of PP7 coat protein dimers into virus-like particles in
      vitro were established. CONCLUSION: The presence of inter-dimer disulfide bonds
      greatly stabilizes the PP7 virus-like particle against thermal denaturation.
      Covalently cross-linking the subunits of the dimers themselves by genetically
      fusing them through a dipeptide linker sequence, offers no further stabilization
      of the VLP, although it does stabilize the dimer. PP7 capsids readily assemble in
      vitro in a reaction that requires RNA.

PMID- 18039381
TI  - Outcomes of patients hospitalized for acute decompensated heart failure: does
      nesiritide make a difference?
AB  - BACKGROUND: Nesiritide is indicated in the treatment of acute decompensated heart
      failure. However, a recent meta-analysis reported that nesiritide may be
      associated with an increased risk of death. Our goal was to evaluate the impact
      of nesiritide treatment on four outcomes among adults hospitalized for congestive
      heart failure (CHF) during a three-year period. METHODS: CHF patients discharged
      between 1/1/2002 and 12/31/2004 from the Adventist Health System, a national, not
      for-profit hospital system, were identified. 25,330 records were included in this
      retrospective study. Nesiritide odds ratios (OR) were adjusted for various
      factors including nine medications and/or an APR-DRG severity score. RESULTS:
      Initially, treatment with nesiritide was found to be associated with a 59% higher
      odds of hospital mortality (Unadjusted OR = 1.59, 95% confidence interval [CI]:
      1.31-1.93). Adjusting for race, low economic status, APR-DRG severity of illness
      score, and the receipt of nine medications yielded a nonsignificant nesiritide OR
      of 1.07 for hospital death (95% CI: 0.85-1.35). Nesiritide was positively
      associated with the odds of prolonged length of stay (all adjusted ORs = 1.66)
      and elevated pharmacy cost (all adjusted ORs > 5). CONCLUSION: In this
      observational study, nesiritide therapy was associated with increased length of
      stay and pharmacy cost, but not hospital mortality. Randomized trials are
      urgently needed to better define the efficacy, if any, of nesiritide in the
      treatment of decompensated heart failure.

PMID- 18039382
TI  - Bias analysis applied to Agricultural Health Study publications to estimate non
      random sources of uncertainty.
AB  - BACKGROUND: The associations of pesticide exposure with disease outcomes are
      estimated without the benefit of a randomized design. For this reason and others,
      these studies are susceptible to systematic errors. I analyzed studies of the
      associations between alachlor and glyphosate exposure and cancer incidence, both
      derived from the Agricultural Health Study cohort, to quantify the bias and
      uncertainty potentially attributable to systematic error. METHODS: For each
      study, I identified the prominent result and important sources of systematic
      error that might affect it. I assigned probability distributions to the bias
      parameters that allow quantification of the bias, drew a value at random from
      each assigned distribution, and calculated the estimate of effect adjusted for
      the biases. By repeating the draw and adjustment process over multiple
      iterations, I generated a frequency distribution of adjusted results, from which
      I obtained a point estimate and simulation interval. These methods were applied
      without access to the primary record-level dataset. RESULTS: The conventional
      estimates of effect associating alachlor and glyphosate exposure with cancer
      incidence were likely biased away from the null and understated the uncertainty
      by quantifying only random error. For example, the conventional p-value for a
      test of trend in the alachlor study equaled 0.02, whereas fewer than 20% of the
      bias analysis iterations yielded a p-value of 0.02 or lower. Similarly, the
      conventional fully-adjusted result associating glyphosate exposure with multiple
      myleoma equaled 2.6 with 95% confidence interval of 0.7 to 9.4. The frequency
      distribution generated by the bias analysis yielded a median hazard ratio equal
      to 1.5 with 95% simulation interval of 0.4 to 8.9, which was 66% wider than the
      conventional interval. CONCLUSION: Bias analysis provides a more complete picture
      of true uncertainty than conventional frequentist statistical analysis
      accompanied by a qualitative description of study limitations. The latter
      approach is likely to lead to overconfidence regarding the potential for causal
      associations, whereas the former safeguards against such overinterpretations.
      Furthermore, such analyses, once programmed, allow rapid implementation of
      alternative assignments of probability distributions to the bias parameters, so
      elevate the plane of discussion regarding study bias from characterizing studies
      as "valid" or "invalid" to a critical and quantitative discussion of sources of
      uncertainty.

PMID- 18039383
TI  - Detection of inflammatory bowel disease by proton magnetic resonance spectroscopy
      (1H MRS) using an animal model.
AB  - BACKGROUND: The aim of this study was to analyze the potential of proton magnetic
      resonance spectroscopy (1H MRS) in diagnosing early inflammatory bowel disease
      (IBD). METHODS: Thirty male Sprague Dawley rats were fed 2% carrageenan in their
      diet for either 1 or 2 weeks. 1H MRS was performed ex-vivo on colonic mucosal
      samples (n = 123) and the spectra were analyzed by a multivariate method of
      analysis. The results of the multivariate analysis were correlated with
      histological analysis performed using H & E stain for the presence of
      inflammation in the samples from each group. RESULTS: Multivariate analysis
      classified the samples in their respective groups with an accuracy of 82%. Our
      region selection algorithm identified four regions in the spectra as being
      discriminatory. The metabolites assigned to these regions include creatine,
      phosphatidylcholine, the -CH2HC= group in fatty acyl chain, and the glycerol
      backbone of lipids. The differences in concentration of these metabolites in each
      group offer insight into the biochemical changes occurring during IBD and confer
      diagnostic potential to 1H MRS as a tool to study colonic inflammation in
      conjunction with biopsy. CONCLUSION: 1H MRS is a sensitive tool to detect early
      colonic inflammation in an animal model of IBD.

PMID- 18039384
TI  - Antihyperlipemic and antihypertensive effects of Spirulina maxima in an open
      sample of Mexican population: a preliminary report.
AB  - BACKGROUND: Spirulina maxima is a filamentous cyanobacterium used as food
      supplement because of its high nutrient contents. It has been experimentally
      proven, in vivo and in vitro that posses several pharmacological properties. The
      purpose of this study was to evaluate the effects of Spirulina maxima orally
      supplied (4.5 g/day, for 6 weeks) to a sample of 36 subjects (16 men and 20
      women, with ages between 18-65 years) on serum lipids, glucose, aminotransferases
      and on blood pressure. The volunteers did not modify their dietary habits or
      lifestyle during the whole experimental period. From each subject, a sample of
      blood was drawn in fasting state of 12 hours to determi the plasma concentrations
      of glucose, triacylglycerols (TAG), total cholesterol (TC), cholesterol
      associated to high density lipoprotein (HDL-C) and aspartate aminotransferase
      (AST). Anthropometric measurements including systolic (SYST-P) and diastolic
      (DIAST-P) blood pressure, height, weight and Body Mass Index (BMI) were also
      recorded. RESULTS: Comparing initial and final data, the results showed that
      there were no significant changes in the values of glucose and AST, but
      significant differences in TAG, TC, and HDL-C, were observed: TAG 233.7 +/- 177.8
      vs. 167.7 +/- 100.7 mg/dL (p < 0.001), TC 181.7 +/- 37.5 vs. 163.5 +/- 34.4 mg/dL
      (p < 0.001), C-HDL 43.5 +/- 14.4 vs. 50 +/- 18.8 mg/dL (p < 0.01). The
      univariated analysis showed that the changes in the HDL-C and TC concentrations
      were dependent on TAG concentration (p = 0.247 and p = 0.108, respectively);
      nevertheless the calculated values for cholesterol associated to low density
      lipoprotein (LDL-C) were significantly reduced by the Spirulina maxima treatment
      but independently of the TAG changes. In addition, significant differences were
      found comparing initial and final SYST-P and DIAST-P blood pressure in both male
      and female: SYST-P male 121 +/- 9 vs. 111 +/- 8 mm Hg (p < 0.01), DIAST-P male 85
      +/- 6.5 vs. 77 +/- 9 mm Hg (p < 0.01); SYST-P female 120 +/- 9.5 vs. 109 +/- 11
      mm Hg (p < 0.002), DIAST-P female 85 +/- 11 vs. 79 +/- 7.5 mm Hg (p < 0.03).
      CONCLUSION: The Spirulina maxima showed a hypolipemic effect, especially on the
      TAG and the LDL-C concentrations but indirectly on TC and HDL-C values. It also
      reduces systolic and diastolic blood pressure.

PMID- 18039385
TI  - Developmental stage of oligodendrocytes determines their response to activated
      microglia in vitro.
AB  - BACKGROUND: Oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes
      are both lost in central nervous system injury and disease. Activated microglia
      may play a role in OPC and oligodendrocyte loss or replacement, but it is not
      clear how the responses of OPCs and oligodendrocytes to activated microglia
      differ. METHODS: OPCs and microglia were isolated from rat cortex. OPCs were
      induced to differentiate into oligodendrocytes with thyroid hormone in defined
      medium. For selected experiments, microglia were added to OPC or oligodendrocyte
      cultures. Lipopolysaccharide was used to activate microglia and microglial
      activation was confirmed by TNFalpha ELISA. Cell survival was assessed with
      immunocytochemistry and cell counts. OPC proliferation and oligodendrocyte
      apoptosis were also assessed. RESULTS: OPCs and oligodendrocytes displayed
      phenotypes representative of immature and mature oligodendrocytes, respectively.
      Activated microglia reduced OPC survival, but increased survival and reduced
      apoptosis of mature oligodendrocytes. Activated microglia also underwent cell
      death themselves. CONCLUSION: Activated microglia may have divergent effects on
      OPCs and mature oligodendrocytes, reducing OPC survival and increasing mature
      oligodendrocyte survival. This may be of importance because activated microglia
      are present in several disease states where both OPCs and mature oligodendrocytes
      are also reacting to injury. Activated microglia may simultaneously have
      deleterious and helpful effects on different cells after central nervous system
      injury.

PMID- 18039386
TI  - Parameters of proteome evolution from histograms of amino-acid sequence
      identities of paralogous proteins.
AB  - BACKGROUND: The evolution of the full repertoire of proteins encoded in a given
      genome is mostly driven by gene duplications, deletions, and sequence
      modifications of existing proteins. Indirect information about relative rates and
      other intrinsic parameters of these three basic processes is contained in the
      proteome-wide distribution of sequence identities of pairs of paralogous
      proteins. RESULTS: We introduce a simple mathematical framework based on a
      stochastic birth-and-death model that allows one to extract some of this
      information and apply it to the set of all pairs of paralogous proteins in H.
      pylori, E. coli, S. cerevisiae, C. elegans, D. melanogaster, and H. sapiens. It
      was found that the histogram of sequence identities p generated by an all-to-all
      alignment of all protein sequences encoded in a genome is well fitted with a
      power-law form approximately p-gamma with the value of the exponent gamma around
      4 for the majority of organisms used in this study. This implies that the intra
      protein variability of substitution rates is best described by the Gamma
      distribution with the exponent alpha approximately 0.33. Different features of
      the shape of such histograms allow us to quantify the ratio between the genome
      wide average deletion/duplication rates and the amino-acid substitution rate.
      CONCLUSION: We separately measure the short-term ("raw") duplication and deletion
      rates , which include gene copies that will be removed soon after the duplication
      event and their dramatically reduced long-term counterparts r(*)dup, r(*)del.
      High deletion rate among recently duplicated proteins is consistent with a
      scenario in which they didn't have enough time to significantly change their
      functional roles and thus are to a large degree disposable. Systematic trends of
      each of the four duplication/deletion rates with the total number of genes in the
      genome were analyzed. All but the deletion rate of recent duplicates r(*)del were
      shown to systematically increase with Ngenes. Abnormally flat shapes of sequence
      identity histograms observed for yeast and human are consistent with lineages
      leading to these organisms undergoing one or more whole-genome duplications. This
      interpretation is corroborated by our analysis of the genome of Paramecium
      tetraurelia where the p-4 profile of the histogram is gradually restored by the
      successive removal of paralogs generated in its four known whole-genome
      duplication events.

PMID- 18039387
TI  - The physical and mental health of a large military cohort: baseline functional
      health status of the Millennium Cohort.
AB  - BACKGROUND: The US military is currently involved in large, lengthy, and complex
      combat operations around the world. Effective military operations require optimal
      health of deployed service members, and both mental and physical health can be
      affected by military operations. METHODS: Baseline data were collected from
      77,047 US service members during 2001-2003 as part of a large, longitudinal,
      population-based military health study (the Millennium Cohort Study). The authors
      calculated unadjusted, adjusted, and weighted means for the Medical Outcomes
      Study Short Form 36-item Survey for Veterans physical (PCS) and mental component
      summary (MCS) scores over a variety of demographic and military characteristics
      at baseline. RESULTS: The unadjusted mean PCS and MCS scores for this study were
      53.4 (95% confidence interval: 53.3-53.4) and 52.8 (95% confidence interval: 52.7
      52.9). Average PCS and MCS scores were slightly more favorable in this military
      sample compared to those of the US general population of the same age and sex.
      Factors independently associated with more favorable health status included male
      gender, being married, higher educational attainment, higher military rank, and
      Air Force service. Combat specialists had similar health status compared to other
      military occupations. Having been deployed to Southwest Asia, Bosnia, or Kosovo
      between 1998 and 2000 was not associated with diminished health status.
      CONCLUSION: The baseline health status of this large population-based military
      cohort is better than that of the US general population of the same age and sex
      distribution over the same time period, especially in older age groups.
      Deployment experiences during the period of 1998-2001 were not associated with
      decreased health status. These data will serve as a useful reference for other
      military health studies and for future longitudinal analyses.

PMID- 18039388
TI  - Geometric least squares means ratios for the analysis of Plasmodium falciparum in
      vitro susceptibility to antimalarial drugs.
AB  - BACKGROUND: The susceptibility of microbes such as Plasmodium falciparum to drugs
      is measured in vitro as the concentration of the drug achieving 50% of maximum
      effect (IC50); values from a population are summarized as geometric means. For
      antimalarial drugs, as well as for antibiotics, assessing changes in microbe
      susceptibility over time under drug pressure would help inform treatment policy
      decisions, but no standard statistical method exists as yet. METHODS: A mixed
      model was generated on loge-transformed IC50 values and calculated geometric
      least squares means (GLSM) with 90% confidence intervals (CIs). In order to
      compare IC50s between years, GLSM ratios (GLSMR) with 90%CIs were calculated and,
      when both limits of the 90%CIs were below or above 100%, the difference was
      considered statistically significant. Results were compared to those obtained
      from ANOVA and a generalized linear model (GLM). RESULTS: GLSMRs were more
      conservative than ANOVA and resulted in lower levels of statistical significance.
      The GLSMRs approach allowed for random effect and adjustment for multiple
      comparisons. GLM was limited in the number of year-to-year comparisons by the
      need for a single reference year. The three analyses yielded generally consistent
      results. CONCLUSION: A robust analytical method can palliate inherent limitations
      of in vitro sensitivity testing. The random effects GLSMRs with adjustment for
      multiple comparisons and 90%CIs require only assumptions on the mixed model to be
      applied. Results are easy to display graphically and to interpret. The GLMSRs
      should be considered as an option for monitoring changes in drug susceptibility
      of P. falciparum malaria and other microbes.

PMID- 18039389
TI  - Can the measurement of brachial artery flow-mediated dilation be applied to the
      acute exercise model?
AB  - The measurement of flow-mediated dilation using high-resolution ultrasound has
      been utilized extensively in interventional trials evaluating the salutary effect
      of drugs and lifestyle modifications (i.e. diet or exercise training) on
      endothelial function; however, until recently researchers have not used flow
      mediated dilation to examine the role of a single bout of exercise on vascular
      function. Utilizing the acute exercise model can be advantageous as it allows for
      an efficient manipulation of exercise variables (i.e. mode, intensity, duration,
      etc.) and permits greater experimental control of confounding variables. Given
      that the application of flow-mediated dilation in the acute exercise paradigm is
      expanding, the purpose of this review is to discuss methodological and
      physiological factors pertinent to flow-mediated dilation in the context of acute
      exercise. Although the scientific rationale for evaluating endothelial function
      in response to acute exercise is sound, few concerns warrant attention when
      interpreting flow-mediated dilation data following acute exercise. The following
      questions will be addressed in the present review: Does the measurement of flow
      mediated dilation influence subsequent serial measures of flow-mediated dilation?
      Do we need to account for diurnal variation? Is there an optimal time to measure
      post-exercise flow-mediated dilation? Is the post-exercise flow-mediated dilation
      reproducible? How is flow-mediated dilation interpreted considering the
      hemodynamic and sympathetic changes associated with acute exercise? Can the
      measurement of endothelial-independent dilation affect the exercise? Evidence
      exists to support the methodological appropriateness for employing flow-mediated
      dilation in the acute exercise model; however, further research is warranted to
      clarify its interpretation following acute exercise.

PMID- 18039390
TI  - Anophthalmia and microphthalmia.
AB  - Anophthalmia and microphthalmia describe, respectively, the absence of an eye and
      the presence of a small eye within the orbit. The combined birth prevalence of
      these conditions is up to 30 per 100,000 population, with microphthalmia reported
      in up to 11% of blind children. High-resolution cranial imaging, post-mortem
      examination and genetic studies suggest that these conditions represent a
      phenotypic continuum. Both anophthalmia and microphthalmia may occur in isolation
      or as part of a syndrome, as in one-third of cases. Anophthalmia/microphthalmia
      have complex aetiology with chromosomal, monogenic and environmental causes
      identified. Chromosomal duplications, deletions and translocations are
      implicated. Of monogenic causes only SOX2 has been identified as a major
      causative gene. Other linked genes include PAX6, OTX2, CHX10 and RAX. SOX2 and
      PAX6 mutations may act through causing lens induction failure. FOXE3 mutations,
      associated with lens agenesis, have been observed in a few microphthalmic
      patients. OTX2, CHX10 and RAX have retinal expression and may result in
      anophthalmia/microphthalmia through failure of retinal differentiation.
      Environmental factors also play a contributory role. The strongest evidence
      appears to be with gestational-acquired infections, but may also include maternal
      vitamin A deficiency, exposure to X-rays, solvent misuse and thalidomide
      exposure. Diagnosis can be made pre- and post-natally using a combination of
      clinical features, imaging (ultrasonography and CT/MR scanning) and genetic
      analysis. Genetic counselling can be challenging due to the extensive range of
      genes responsible and wide variation in phenotypic expression. Appropriate
      counselling is indicated if the mode of inheritance can be identified.
      Differential diagnoses include cryptophthalmos, cyclopia and synophthalmia, and
      congenital cystic eye. Patients are often managed within multi-disciplinary teams
      consisting of ophthalmologists, paediatricians and/or clinical geneticists,
      especially for syndromic cases. Treatment is directed towards maximising existing
      vision and improving cosmesis through simultaneous stimulation of both soft
      tissue and bony orbital growth. Mild to moderate microphthalmia is managed
      conservatively with conformers. Severe microphthalmia and anophthalmia rely upon
      additional remodelling strategies of endo-orbital volume replacement (with
      implants, expanders and dermis-fat grafts) and soft tissue reconstruction. The
      potential for visual development in microphthalmic patients is dependent upon
      retinal development and other ocular characteristics.

PMID- 18039392
TI  - Add-on quetiapine in the treatment of major depressive disorder in elderly
      patients with cerebrovascular damage.
AB  - BACKGROUND: Depressive episodes in elderly patients with cerebrovascular damage
      are characterized by poor responses to standard antidepressants. Recent reports
      have suggested that the atypical antipsychotic, quetiapine may have
      antidepressant properties and, in mice, may prevents memory impairment and
      hippocampus neurodegeneration induced by global cerebral ischemia. OBJECTIVE: To
      evaluate the efficacy of combination therapy with quetiapine in depressed elderly
      patients with cerebrovascular damage. METHODS: An open-label, 6-month follow-up
      study of patients with major depressive disorder (DSM-IV) and cerebral
      abnormalities (assessed by MRI) without severe cognitive impairment. Patients who
      had not responded to standard antidepressants (months of treatment 6.5 +/- 7.2)
      additionally received quetiapine (300 +/- 111 mg/d). Patients were evaluated at
      baseline (t0) and Months 1, 3, and 6 (t1, t3, t6) using the Clinical Global
      Impressions Scale for Severity (CGI-S) and the Hamilton Depression Rating Scale
      (HAM-D). RESULTS: Nine patients were included in the study, with a mean age of
      72.8 +/- 9.4 years. CGI-S scores decreased from baseline to Month 6: 5.8 +/- 0.7
      (t0), 5.4 +/- 0.7 (t1), 5.0 +/- 0.8 (t3), and 4.5 +/- 1.0 (t6), with a
      significant improvement at 6 months compared with baseline (P = 0.006). A
      significant improvement over the 6-month period was also observed with HAM-D
      scores (t0 = 27.2 +/- 4.0, t6 = 14.8 +/- 3.8, P < 0.001). CONCLUSION: In this
      study, quetiapine was efficacious as combination therapy in depressed elderly
      patients with cerebrovascular damage. The promising results from this study
      warrant confirmation in large, randomized, double-blind, placebo-controlled
      studies.

PMID- 18039391
TI  - Baicalein inhibits IL-1beta- and TNF-alpha-induced inflammatory cytokine
      production from human mast cells via regulation of the NF-kappaB pathway.
AB  - BACKGROUND: Human mast cells are multifunctional cells capable of a wide variety
      of inflammatory responses. Baicalein (BAI), isolated from the traditional Chinese
      herbal medicine Huangqin (Scutellaria baicalensis Georgi), has been shown to have
      anti-inflammatory effects. We examined its effects and mechanisms on the
      expression of inflammatory cytokines in an IL-1beta- and TNF-alpha-activated
      human mast cell line, HMC-1. METHODS: HMC-1 cells were stimulated either with IL
      1beta (10 ng/ml) or TNF-alpha (100 U/ml) in the presence or absence of BAI. We
      assessed the expression of IL-6, IL-8, and MCP-1 by ELISA and RT-PCR, NF-kappaB
      activation by electrophoretic mobility shift assay (EMSA), and IkappaBalpha
      activation by Western blot. RESULTS: BAI (1.8 to 30 muM) significantly inhibited
      production of IL-6, IL-8, and MCP-1 in a dose-dependent manner in IL-1beta
      activated HMC-1. BAI (30 muM) also significantly inhibited production of IL-6, IL
      8, and MCP-1 in TNF-alpha-activated HMC-1. Inhibitory effects appear to involve
      the NF-kappaB pathway. BAI inhibited NF-kappaB activation in IL-1beta- and TNF
      alpha-activated HMC-1. Furthermore, BAI increased cytoplasmic IkappaBalpha
      proteins in IL-1beta- and TNF-alpha-activated HMC-1. CONCLUSION: Our results
      showed that BAI inhibited the production of inflammatory cytokines through
      inhibition of NF-kappaB activation and IkappaBalpha phosphorylation and
      degradation in human mast cells. This inhibitory effect of BAI on the expression
      of inflammatory cytokines suggests its usefulness in the development of novel
      anti-inflammatory therapies.

PMID- 18039393
TI  - Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer.
AB  - PURPOSE: An open-label Phase 1 study of recombinant prime-boost poxviruses
      targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted
      to determine safety, tolerability and obtain preliminary data on immune response
      and survival. PATIENTS AND METHODS: Ten patients with advanced pancreatic cancer
      were treated on a Phase I clinical trial. The vaccination regimen consisted of
      vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA) and mucin
      1 (MUC-1) with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM)
      (PANVAC-V) and fowlpox virus expressing the same antigens and costimulatory
      molecules (PANVAC-F). Patients were primed with PANVAC-V followed by three
      booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating
      factor (GM-CSF) was used as a local adjuvant after each vaccination and for 3
      consecutive days thereafter. Monthly booster vaccinations for up to 12 months
      were provided for patients without progressive disease. Peripheral blood was
      collected before, during and after vaccinations for immune analysis. RESULTS: The
      most common treatment-related adverse events were mild injection-site reactions.
      Antibody responses against vaccinia virus was observed in all 10 patients and
      antigen-specific T cell responses were observed in 5 out of 8 evaluable patients
      (62.5%). Median overall survival was 6.3 months and a significant increase in
      overall survival was noted in patients who generated anti CEA- and/or MUC-1
      specific immune responses compared with those who did not (15.1 vs 3.9 months,
      respectively; P = .002). CONCLUSION: Poxvirus vaccination is safe, well
      tolerated, and capable of generating antigen-specific immune responses in
      patients with advanced pancreatic cancer.

PMID- 18039394
TI  - Gene regulatory networks in lactation: identification of global principles using
      bioinformatics.
AB  - BACKGROUND: The molecular events underlying mammary development during pregnancy,
      lactation, and involution are incompletely understood. RESULTS: Mammary gland
      microarray data, cellular localization data, protein-protein interactions, and
      literature-mined genes were integrated and analyzed using statistics, principal
      component analysis, gene ontology analysis, pathway analysis, and network
      analysis to identify global biological principles that govern molecular events
      during pregnancy, lactation, and involution. CONCLUSION: Several key principles
      were derived: (1) nearly a third of the transcriptome fluctuates to build, run,
      and disassemble the lactation apparatus; (2) genes encoding the secretory
      machinery are transcribed prior to lactation; (3) the diversity of the endogenous
      portion of the milk proteome is derived from fewer than 100 transcripts; (4)
      while some genes are differentially transcribed near the onset of lactation, the
      lactation switch is primarily post-transcriptionally mediated; (5) the secretion
      of materials during lactation occurs not by up-regulation of novel genomic
      functions, but by widespread transcriptional suppression of functions such as
      protein degradation and cell-environment communication; (6) the involution switch
      is primarily transcriptionally mediated; and (7) during early involution, the
      transcriptional state is partially reverted to the pre-lactation state. A new
      hypothesis for secretory diminution is suggested - milk production gradually
      declines because the secretory machinery is not transcriptionally replenished. A
      comprehensive network of protein interactions during lactation is assembled and
      new regulatory gene targets are identified. Less than one fifth of the
      transcriptionally regulated nodes in this lactation network have been previously
      explored in the context of lactation. Implications for future research in mammary
      and cancer biology are discussed.

PMID- 18039396
TI  - The nomenclature, definition and classification of cardiac structures in the
      setting of heterotaxy.
AB  - In 2000, The International Nomenclature Committee for Pediatric and Congenital
      Heart Disease was established. This committee eventually evolved into the
      International Society for Nomenclature of Paediatric and Congenital Heart
      Disease. The working component of this international nomenclature society has
      been The International Working Group for Mapping and Coding of Nomenclatures for
      Paediatric and Congenital Heart Disease, also known as the Nomenclature Working
      Group. The Nomenclature Working Group created the International Paediatric and
      Congenital Cardiac Code, which is available for free download from the internet
      at [http://www.IPCCC.NET]. In previous publications from the Nomenclature Working
      Group, unity has been produced by cross-mapping separate systems for coding, as
      for example in the treatment of the functionally univentricular heart,
      hypoplastic left heart syndrome, or congenitally corrected transposition. In this
      manuscript, we review the nomenclature, definition, and classification of
      heterotaxy, also known as the heterotaxy syndrome, placing special emphasis on
      the philosophical approach taken by both the Bostonian school of segmental
      notation developed from the teachings of Van Praagh, and the European school of
      sequential segmental analysis. The Nomenclature Working Group offers the
      following definition for the term "heterotaxy": "Heterotaxy is synonymous with
      'visceral heterotaxy' and 'heterotaxy syndrome'. Heterotaxy is defined as an
      abnormality where the internal thoraco-abdominal organs demonstrate abnormal
      arrangement across the left-right axis of the body. By convention, heterotaxy
      does not include patients with either the expected usual or normal arrangement of
      the internal organs along the left-right axis, also known as 'situs solitus', nor
      patients with complete mirror-imaged arrangement of the internal organs along the
      left-right axis also known as 'situs inversus'." "Situs ambiguus is defined as an
      abnormality in which there are components of situs solitus and situs inversus in
      the same person. Situs ambiguus, therefore, can be considered to be present when
      the thoracic and abdominal organs are positioned in such a way with respect to
      each other as to be not clearly lateralised and thus have neither the usual, or
      normal, nor the mirror-imaged arrangements."The heterotaxy syndrome as thus
      defined is typically associated with complex cardiovascular malformations. Proper
      description of the heart in patients with this syndrome requires complete
      description of both the cardiac relations and the junctional connections of the
      cardiac segments, with documentation of the arrangement of the atrial appendages,
      the ventricular topology, the nature of the unions of the segments across the
      atrioventricular and the ventriculoarterial junctions, the infundibular
      morphologies, and the relationships of the arterial trunks in space. The position
      of the heart in the chest, and the orientation of the cardiac apex, must also be
      described separately. Particular attention is required for the venoatrial
      connections, since these are so often abnormal. The malformations within the
      heart are then analysed and described separately as for any patient with
      suspected congenital cardiac disease. The relationship and arrangement of the
      remaining thoraco-abdominal organs, including the spleen, the lungs, and the
      intestines, also must be described separately, because, although common patterns
      of association have been identified, there are frequent exceptions to these
      common patterns. One of the clinically important implications of heterotaxy
      syndrome is that splenic abnormalities are common. Investigation of any patient
      with the cardiac findings associated with heterotaxy, therefore, should include
      analysis of splenic morphology. The less than perfect association between the
      state of the spleen and the form of heart disease implies that splenic morphology
      should be investigated in all forms of heterotaxy, regardless of the type of
      cardiac disease. The splenic morphology should not be used to stratify the form
      of disease within the heart, and the form of cardiac disease should not be used
      to stratify the state of the spleen. Intestinal malrotation is another frequently
      associated lesion that must be considered. Some advocate that all patients with
      heterotaxy, especially those with isomerism of the right atrial appendages or
      asplenia syndrome, should have a barium study to evaluate for intestinal
      malrotation, given the associated potential morbidity. The cardiac anatomy and
      associated cardiac malformations, as well as the relationship and arrangement of
      the remaining thoraco-abdominal organs, must be described separately. It is only
      by utilizing this stepwise and logical progression of analysis that it becomes
      possible to describe correctly, and to classify properly, patients with
      heterotaxy.

PMID- 18039395
TI  - Conservation and divergence of gene families encoding components of innate immune
      response systems in zebrafish.
AB  - BACKGROUND: The zebrafish has become a widely used model to study disease
      resistance and immunity. Although the genes encoding many components of immune
      signaling pathways have been found in teleost fish, it is not clear whether all
      components are present or whether the complexity of the signaling mechanisms
      employed by mammals is similar in fish. RESULTS: We searched the genomes of the
      zebrafish Danio rerio and two pufferfish for genes encoding components of the
      Toll-like receptor and interferon signaling pathways, the NLR (NACHT-domain and
      leucine rich repeat containing) protein family, and related proteins. We find
      that most of the components known in mammals are also present in fish, with
      clearly recognizable orthologous relationships. The class II cytokines and their
      receptors have diverged extensively, obscuring orthologies, but the number of
      receptors is similar in all species analyzed. In the family of the NLR proteins,
      the canonical members are conserved. We also found a conserved NACHT-domain
      protein with WD40 repeats that had previously not been described in mammals.
      Additionally, we have identified in each of the three fish a large species
      specific subgroup of NLR proteins that contain a novel amino-terminal domain that
      is not found in mammalian genomes. CONCLUSION: The main innate immune signaling
      pathways are conserved in mammals and teleost fish. Whereas the components that
      act downstream of the receptors are highly conserved, with orthologous sets of
      genes in mammals and teleosts, components that are known or assumed to interact
      with pathogens are more divergent and have undergone lineage-specific expansions.

PMID- 18039397
TI  - Controversies, genetics, diagnostic assessment, and outcomes relating to the
      heterotaxy syndrome.
AB  - How best to analyse and describe the features of the situation commonly known as
      "visceral heterotaxy" remains controversial. Much of the disagreement devolves on
      how to deal with the concept of isomerism. In the opinion of some, the concept of
      bilateral right-sidedness and bilateral left-sidedness, while useful in helping
      to remember which abnormalities are likely to occur in asplenia or polysplenia,
      should not be granted the status of a specific "situs", since there are numerous
      examples of exceptions to these patterns. On the other hand, those who favour the
      concept of isomerism point out that, when describing only the heart, and taking
      the structure of the atrial appendages as the starting point for analysis, basing
      this on the extent of the pectinate muscles relative to the atrioventricular
      junctions, then the only possible arrangements for the appendages are the usual
      one, its mirror-image, and the two situations in which appendages of comparable
      morphology are found on both sides of the heart, these being the arrangements of
      right or left isomerism. It is certainly the case that the arrangement of the
      organs is not always in harmony with the arrangement of the atrial appendages,
      but those circumstances, in which there is disharmony, can readily be described
      by paying specific attention to each series of organs. On this basis, in this
      review, we describe the approach to heterotaxy, and isomerism of the atrial
      appendages, in terms of the genetic background, the diagnosis, and outcomes after
      cardiac surgery. Attention is given to the various diagnostic modalities,
      including fetal and postnatal echocardiography, recent tomographic and magnetic
      resonance imaging techniques, and the time-honoured approach using angiography.

PMID- 18039399
TI  - Identification, imaging, functional assessment and management of congenital
      coronary arterial abnormalities in children.
AB  - The coronary arteries, the vessels through which both substrate and oxygen are
      provided to the cardiac muscle, normally arise from paired stems, right and left,
      each arising from a separate and distinct sinus of the aortic valve. The right
      coronary artery runs through the right atrioventricular groove, terminating in
      the majority of instances in the inferior interventricular groove. The main stem
      of the left coronary artery bifurcates into the anterior descending, or
      interventricular, and the circumflex branches. Origin of the anterior descending
      and circumflex arteries from separate orifices from the left sinus of Valsalva
      occurs in about 1% of the population, while it is also frequent to find the
      infundibular artery arising as a separate branch from the right sinus of
      Valsalva. Anomalies of the coronary arteries can result from rudimentary
      persistence of an embryologic coronary arterial structure, failure of normal
      development or normal atrophy as part of development, or misplacement of
      connection of a an otherwise normal coronary artery. Anomalies, therefore, can be
      summarized in terms of abnormal origin or course, abnormal number of coronary
      arteries, lack of patency of the orifice of coronary artery, or abnormal
      connections of the arteries. Anomalous origin of the left coronary artery from
      the pulmonary trunk occurs with an incidence of approximately 1 in 300,000
      children. The degree of left ventricular dysfunction produced likely relates to
      the development of collateral vessels that arise from the right coronary artery,
      and provide flow into the left system. Anomalous origin of either the right or
      the left coronary artery from the opposite sinus of Valsalva can be relatively
      innocuous, but if the anomalous artery takes an interarterial course between the
      pulmonary trunk and the aorta, this can underlie sudden death, almost invariably
      during or immediately following strenuous exercise or competitive sporting
      events. Distal anomalies of the coronary arteries most commonly involve abnormal
      connections, or fistulas, between the right or left coronary arterial systems and
      a chamber or vessel. We discuss the current techniques available for imaging
      these various lesions, along with their functional assessment, concluding with a
      summary of current strategies for management.

PMID- 18039398
TI  - Functional state of patients with heterotaxy syndrome following the Fontan
      operation.
AB  - BACKGROUND: Children born with heterotaxy syndromes have poorer outcomes compared
      with children born with comparable cardiac lesions requiring similar surgical
      palliation. Heterotaxy has been reported as a separate risk factor for mortality
      and increased morbidity in a series of Fontan operations reported from single
      centres. Little is known, however, about the functional state of surviving
      patients with heterotaxy following a Fontan operation. METHODS: In the
      multicentric cross-sectional study carried out by the Pediatric Heart Network of
      546 survivors of the Fontan procedure, the patients, aged from 6 to 18 years,
      underwent evaluation by echocardiography, exercise testing, electrocardiography,
      magnetic resonance imaging, and functional health status questionnaires compiled
      by the patients and their parents. Heterotaxy was identified in 42 patients (8%).
      Medical and patient characteristics were compared between those with heterotaxy
      and the remaining 504 patients who did not have heterotaxy. RESULTS: Patients
      with heterotaxy had their Fontan procedure performed at a later age, with a
      median of 3.9 years versus 2.8 years (p=0.001) and had volume-unloading surgery
      performed later, at a median age of 1.4 versus 0.9 years (p=0.008). These
      patients had significantly different ventricular and atrioventricular valvar
      morphology, as well as a higher incidence of systemic and pulmonary venous
      abnormalities. They had a higher incidence of prior surgery to the pulmonary
      veins, at 21 versus 0.4%. The type of Fontan procedure was different, but no
      difference was detected in length of stay in hospital, or the number of
      postoperative complications. Sinus rhythm was less common, at 44 versus 71%,
      (p=0.002), and history of atrial arrhythmias more common, at 19 versus 8%,
      (p=0.018) in those with heterotaxy. Echocardiography revealed a greater degree
      atrioventricular valvar regurgitation, lower indexed stroke volume, and greater
      Tei index. Exercise performance, levels of brain natriuretic peptide in the
      serum, and summary and domain scores from health status questionnaires, were not
      different from those not having heterotaxy. CONCLUSIONS: The study illustrates a
      profile of characteristics, medical history, functional health state, and markers
      of ventricular performance in patients with heterotaxy after the Fontan
      procedure. Despite obvious anatomic differences, and some differences in
      echocardiography and heart rhythm, there were no important differences in
      exercise performance or functional health state between these patients and other
      survivors of the Fontan procedure.

PMID- 18039400
TI  - Evolution of strategies for management of the patent arterial duct.
AB  - Persistent patency of the arterial duct represents one of the most common lesions
      in the field of congenital cardiac disease. The strategies for management
      continue to evolve. In this review, we focus on management beyond the neonatal
      period. We review the temporal evolution of strategies for management, illustrate
      the currently available the techniques for permanent closure of the patent
      arterial duct, review the expected outcomes after closure, discuss the current
      controversy over the appropriate treatment of the so-called "silent" duct, and
      provide recommendations for the current state of management of patients with
      persistent patency of the arterial duct outside of the neonatal period.At the
      Congenital Heart Institute of Florida, we now recommend closure of all patent
      arterial ducts, regardless of their size. Before selecting and performing the
      type of procedure, we explain the natural history of the persistently patent
      arterial duct to the parents or legal guardian of the child. Particular emphasis
      is placed on the risks of endocarditis, including the recognition that many cases
      of endocarditis may not be preventable. The devastating effects of endocarditis,
      coupled with the perception of more anecdotal reports of endocarditis with the
      silent duct, as well as the low risk of interventions, has led us to recommend
      closure of the patent arterial duct in these situations. We now recommend
      intervention, after informed consent, for all patients with a patent arterial
      duct regardless of size, including those in which the patent duct is "silent". We
      recognize, however, that this remains a controversial topic, especially given the
      new recommendations for endocarditis prophylaxis from American Heart Association.
      Since 2003, our strategy for closure of the patent arterial duct has changed
      subsequent to the availability of the Amplatzer occluder. This new device has
      allowed significantly larger patent arterial ducts to be closed with
      interventional catheterization procedures that in the past would have been closed
      at surgery. During the interval between 2002 and 2006 inclusive, the overall
      surgical volume at our Institute has been stable. Over this period, the number of
      patients undergoing surgical ligation of the patent arterial duct has decreased,
      with this decline in volume most notable for the subgroup of patients weighing
      more than five kilograms. This decrease has been especially notable in
      thoracoscopic procedures and is attributable to the increased ability to close
      larger ducts using the Amplatzer occluder. For infants with symptomatic pulmonary
      overcirculation weighing less than 5 kilograms, our preference is for the
      surgical approach. For patients who have ductal calcification, significant
      pleural scarring, or "window-like" arterial ducts, video-assisted ligation is not
      an option and open surgical techniques are used. When video-assisted ligation is
      possible, the approach is based on family and surgeon preference. When open
      thoracotomy is selected, we usually use a muscle-sparing left posterolateral
      thoracotomy. For patients weighing more than 5 kilograms, we currently recommend
      percutaneous closure for all patent arterial ducts as the first intervention,
      reserving surgical treatment for those cases that are not amenable to the
      percutaneous approach. For symptomatic infants weighing greater than 5 kilogram
      with large ducts, we prefer to use the Amplatzer occluder. In rare instances, the
      size of the required ductal occluder is so large that either encroachment into
      the aorta or pulmonary arteries is noted, and the device is removed. The child is
      then referred for surgical closure. We can now often predict via echocardiography
      that a duct is too large for transcatheter closure, even with the Amplatzer
      occluder, and refer these patients directly to surgery. For patients with an
      asymptomatic patent arterial duct, we prefer to wait until the weight is from 10
      to 12 kilograms, or they are closer to 2 years of age. If the patent arterial
      duct is greater than 2.0 to 2.5 millimetres in diameter, our preference is to use
      the Amplatzer occluder. For smaller ducts, we typically use stainless steel
      coils. Using this strategy, we close all patent arterial ducts, regardless of
      their size.

PMID- 18039401
TI  - Hypoplastic left heart syndrome: consensus and controversies in 2007.
AB  - Variability in practice can be considered to foster clinical innovation, and
      allow for individualized therapeutic plans and independence of practitioners. The
      Institute of Medicine, however, has issued a report suggesting that variability
      in patterns of practice are "illogical", and should be avoided whenever possible.
      Perhaps nowhere in the field of congenital cardiac disease is variability in
      practice more apparent than in the management of hypoplastic left heart syndrome.
      This review assesses the variability in practice at a large number of centres
      that manage neonates with hypoplastic left heart syndrome, with an emphasis on
      practice before, during, and after the first stage of the Norwood sequence of
      operations. We also suggest changes in future strategies for research. In March,
      2007, colleagues were contacted to respond to an internet-based survey using
      commercially available software (www.surveymonkey.com) to collect responses about
      the management practices for neonates with "straight-forward" hypoplastic left
      heart syndrome. No attempt was made to correlate management practices with any
      measures of outcome, as neither the practices themselves, nor the outcomes of
      interest, could be externally validated. Data is reported from 52 centers thought
      to manage over 1000 neonates with hypoplastic left heart syndrome on an annual
      basis. The first stage of the Norwood sequence was "recommended" to families by
      approximately five-sixths (86.5%) of the centres. No centre recommended primary
      cardiac transplantation, a "hybrid" approach, or non-intervention. In 7 centres
      (14.5%), it was reported that there was discussion of some or all of the above
      options, but ultimately the families decided upon the appropriate strategy. Most
      centres preferentially used antegrade cerebral perfusion (54%) in contrast to
      deep hypothermia with circulatory arrest (24%), albeit that 11% of centres used a
      combination of these techniques and in 9% the support strategy was based on
      surgeon preference. The source of flow of blood for the lungs following the first
      stage of reconstruction was also highly variable. Of the 51 centres that
      responded to the question, 13 (25.5%) were participating in a multi-centric
      randomized clinical trial comparing the modified Blalock-Taussig shunt to the
      conduit placed from the right ventricle to the pulmonary arteries, the so-called
      "Sano" modification. Of the remaining 38 centres, 18 "usually" placed a conduit
      from the right ventricle to the pulmonary artery, 14 "usually" placed a modified
      Blalock-Taussig shunt, and at six centres, the decision was made "based upon the
      preference of the surgeon and/or the cardiologist". Similarly, significant
      variability in practice was evident in preoperative management, other surgical
      strategies, postoperative medical support, monitoring and discharge planning.
      Other than the randomized clinical trial of shunt type, no other medical or
      surgical management strategy was currently under investigation in a multi-centric
      or randomized trial in the centres who responded to the survey. The survey
      emphasises the extreme variability in our current practices for treatment of
      children with hypoplastic left heart syndrome. While there are some areas for
      which there is consensus in management, the majority of our practices are
      variable between and within centres. These results emphasize that large
      multicentric trials and registries are necessary to improve care, and to answer
      important clinical questions, emphasizing the need to shift from analysis of
      experiences of single centres to multi-centric and multi-disciplinary
      collaboration.

PMID- 18039402
TI  - Caring for adults with congenital cardiac disease: successes and challenges for
      2007 and beyond.
AB  - Patients with congenital cardiac disease require lifelong medical care. Current
      challenges that face practitioners who care for adults with congenital heart
      disease include identifying the best location for procedures, which could be a
      children's hospital, an adult hospital, or a tertiary care facility; providing
      appropriate antenatal management of pregnant women with congenitally malformed
      hearts, and continuing this care in the peripartum period; and securing the
      infrastructure and expertise of the non-cardiac subspecialties, such as
      nephrology, hepatology, pulmonary medicine, and haematology. The objectives of
      this review are to outline the common problems that confront this population of
      patients and the medical community, to identify challenges encountered in
      establishing a programme for care of adults with congenitally malformed hearts,
      and to review the spectrum of disease and operations that have been identified in
      a high volume tertiary care centre for adult patients with congenital cardiac
      disease. Three chosen examples of the fundamental problems facing the
      practitioner and patient in the United States of America in 2007 are the
      neglected patient with congenital cardiac disease, weak infrastructure for adults
      with congenital cardiac disease, and family planning and management of pregnancy
      for patients with congenital cardiac disease. Patients with adult congenital
      cardiac disease often do not receive appropriate surveillance. Three fundamental
      reasons for this problem are, first, that most adults with congenitally malformed
      hearts have been lost to follow-up by specialists, and are either receiving
      community care or no care at all. Second, patients and their families have not
      been educated about their malformed hearts, what to expect, and how to protect
      their interests most effectively. Third, adult physicians have not been educated
      about the complexity of the adult with a congenitally malformed heart. This
      combination can be fatal for adults with complications related to their
      congenitally malformed heart, or its prior treatment. Two solutions would improve
      surveillance and care for the next generation of patients coming out of the care
      of paediatric cardiologists. The first would be to educate patients and their
      families during childhood and adolescence. They would learn the names of the
      diagnoses and treatments, the problems they need to anticipate and avoid, the
      importance of expert surveillance, career and family planning information, and
      appropriate self-management. The second solution would be to encourage an orderly
      transfer of patients from paediatric to adult practice, usually at about 18 years
      of age, and at the time of graduation from high school. Clinics for adults with
      congenital cardiac disease depend upon multidisciplinary collaboration with
      specialties in areas such as congenital cardiac imaging, diagnostic and
      interventional catheterization, congenital cardiac surgery and anaesthesia, heart
      failure, transplantation, electrophysiology, reproductive and high risk pregnancy
      services, genetics, pulmonary hypertension, hepatology, nephrology, haematology,
      and others. None of these services are easily available "off the rack", although
      with time, experience, and determination, these services can develop very well.
      Facilities with experienced personnel to provide competent care for adults with
      congenital cardiac disease are becoming increasingly available. Parents and
      patients should learn that these facilities exist, and be directed to one by
      their paediatric caregivers when the time comes for transition to adult care.
      With the steady increase in the number of adults with congenital heart disease,
      an ever increasing number of women with such disease are becoming pregnant.
      Services are not widely available to assess competently and plan a pregnancy for
      those with more complex disease. It is essential to have a close interplay
      between the obstetrician, the adult congenital cardiologist, the fetal medicine
      perinatologist, and neonatologist. In both a community based programme and a
      tertiary care centre, the nuances and complexities of congenital cardiac anatomy,
      coupled with the high probability of previous operation during childhood, makes
      the trained congenital cardiothoracic surgeon best suited to deal with the
      surgical needs of this growing population. It is clear that the majority of
      adults with congenital heart disease are not "cured", but require lifelong
      comprehensive care from specialists who have expertise in this complex arena.
      There is a growing cadre of healthcare professionals dedicated to improving the
      care of these patients. More information has become available about their care,
      and will be improved upon in the next decade. With the support of the general
      paediatric and paediatric cardiologic communities, and of the Adult Congenital
      Heart Association, and with the persistence of the providers of care for adults
      with congenital cardiac disease currently staffing clinics, the care of these
      patients should become more secure in the next decade as we mature our
      capabilities.

PMID- 18039403
TI  - Is there still a role for cardiac autopsy in 2007?
AB  - Concerns have emerged in recent years with regard to the role to be played by the
      pathologist in reaching a final diagnosis. When considering the field of the
      congenitally malformed heart, it is true that the richness of detail now provided
      by imaging techniques is truly amazing. Alongside these developments, there has
      also been a significant decline in the number of autopsies performed in tertiary
      medial centres around the World. In this review, we consider some of the factors
      that have contributed to this decrease in autopsies, and review the reasons why
      strong steps should be taken to reverse this trend. When considering the reasons
      for the decline in autopsies, there can be little doubt that the scandal
      devolving on inappropriate retention of organs, which came to light in the United
      Kingdom, but which had reverberations throughout the World, contributed in no
      small way to the reticence of families to grant appropriate permission to conduct
      a post-mortem examination. It is sincerely hoped that the changes in practise
      that followed these revelations will stop, and indeed reverse, this unfortunate
      decline. The inappropriate retention of organs came into the public domain in an
      attempt to emphasise the value of the autopsy in clinical practise, research, and
      education. All of these good reasons for performing the autopsy remain. From the
      stance of education, we emphasise the importance of retaining existing archives,
      which have long since proved their value. From the stance of improving clinical
      practise, we reiterate that the attitude of the morphologist, working side-by
      side with the clinician or surgeon, has always been fundamental in expanding this
      aspect of knowledge. We recognise, nonetheless, that performance of the autopsy
      still carries financial considerations. In this respect, when considering the
      congenitally malformed heart, we stress the option of having the pathologist
      working in harness with an experienced cardiac morphologist, or alternatively
      with a properly trained pathologist's assistant. In terms of training, we show
      how, with the advantage of a few simple rules, it becomes an easy matter to
      describe and analyse the congenitally malformed heart. Thereafter, having
      reviewed means of increasing the number of autopsies, and discussing new
      techniques, we complete our review with a detailed account of the fetal,
      perinatal, and paediatric autopsy in the patients with a congenitally malformed
      heart, taking particular account of the role to be played by the properly trained
      pathologist's assistant.

PMID- 18039404
TI  - Cardiac extracorporeal life support: state of the art in 2007.
AB  - Mechanical circulatory support is an invaluable tool in the care of children with
      severe refractory cardiac and or pulmonary failure. Two forms of mechanical
      circulatory support are currently available to neonates, infants, and smaller
      children, namely extracorporeal membrane oxygenation and use of a ventricular
      assist device, with each technique having unique advantages and disadvantages.
      The intra-aortic balloon pump is a third form of mechanical support that has been
      successfully used in larger children, adolescents, and adults, but has limited
      applicability in smaller children. In this review, we discuss the current
      experiences with extracorporeal membrane oxygenation and ventricular assist
      devices in children with cardiac disease.A variety of forms of mechanical
      circulatory support are available for children with cardiopulmonary dysfunction
      refractory to conventional management. These devices require extensive resources,
      both human and economic. Extracorporeal membrane oxygenation can be effectively
      used in a variety of settings to provide support to critically-ill patients with
      cardiac disease. Careful selection of patients and timing of intervention remains
      challenging. Special consideration should be given to children with cardiac
      disease with regard to anatomy, physiology, cannulation, and circuit management.
      Even though exciting progress is being made in the development of ventricular
      assist devices for long-term mechanical support in children, extracorporeal
      membrane oxygenation remains the mainstay of mechanical circulatory support in
      children with complex anatomy, particularly those needing rapid resuscitation and
      those with a functionally univentricular circulation.As the familiarity and
      experience with extracorporeal membrane oxygenation has grown, new indications
      have evolved, including emergent resuscitation. This utilization has been termed
      extracorporeal cardiopulmonary resuscitation. The literature supporting emergent
      cardiopulmonary support is mounting. Reasonable survival rates have been achieved
      after initiation of support during active compressions of the chest following in
      hospital cardiac arrest. Due to the limitations of conventional circuits for
      extracorporeal membrane oxygenation, some centres have developed novel systems
      for rapid cardiopulmonary support. Many centres previously considered a
      functionally univentricular circulation to be a contraindication to
      extracorporeal membrane oxygenation, but improved results have been achieved
      recently with this complex subset of patients. The registry of the Extracorporeal
      Life Support Organization recently reported the outcome of extracorporeal life
      support used in neonates for cardiac indications from 1996 to 2000. Of the 740
      neonates who were placed on extracorporeal life support for cardiac indications,
      118 had hypoplastic left heart syndrome. There was no significant difference in
      survival between these patients and those with other defects. It is now common to
      use extracorporeal membrane oxygenation to support patients with a functionally
      univentricular circulation, and reasonable survival rates are to be expected.
      Although extracorporeal membrane oxygenation has become a standard of care for
      many paediatric centres, its use is limited to those patients who require only
      short-term cardiopulmonary support. Mechanical ventricular assist devices have
      become standard therapy for adults with cardiac failure refractory to maximal
      medical management. Several devices are readily available in the United States of
      America for adults, but there are fewer options available to children. Over the
      last few years, substantial progress has been made in paediatric mechanical
      support. Ventricular assist devices are being used with increasing frequency in
      children with cardiac failure refractory to medical therapy for primary treatment
      as a long-term bridge to recovery or transplantation. The paracorporeal,
      pneumatic, pulsatile "Berlin Heart" ventricular assist device is being used with
      increasing frequency in Europe and North America to provide univentricular and
      biventricular support. With this device, a patient can be maintained on
      mechanical circulatory support while extubated, being mobilized, and feeding by
      mouth. Mechanical circulatory support should be anticipated, and every attempt
      must be made to initiate support "urgently" rather than "emergently", before the
      presence of dysfunction of end organs or circulatory collapse. In an emergency,
      these patients can be resuscitated with extracorporeal membrane oxygenation and
      subsequently transitioned to a long-term ventricular assist device after a period
      of stability.

PMID- 18039406
TI  - Improving safety for children with cardiac disease.
AB  - The complexity of the modern systems providing health care presents a unique
      challenge in delivering care of the required quality in a safe environment.
      Issues of safety have been thrust into the limelight because of adverse events
      highly publicized in the general media. In the United States of America,
      improving the safety and quality in health care has been set forth as a priority
      for improvements in the 21st century in the report from the Institute of
      Medicine. Many measures have now been initiated for improving the safety of
      patients at hospital, regional, and national level, and through initiatives
      sponsored by governments and private organizations. In this review, we summarize
      known concepts and current issues on the safety of patients, and their
      applicability to children with congenital cardiac disease. Prior to examining the
      issues of medical error and safety, it is important to define the terminology. An
      error is defined as the failure of a planned action to be completed as intended,
      also known as an execution error, or the use of a wrong plan to achieve an aim,
      this representing a planning error. An active error is an error that occurs at
      the level of the frontline operator, and the effects of which are felt
      immediately. A latent error is an error in the design, organization, training and
      maintenance, that leads to operator errors, and the effects of which are
      typically dormant in the system for lengthy periods of time. Latent errors may
      cause harm given the right circumstances and environment. An adverse event is
      defined as an injury resulting from medical intervention. A preventable adverse
      event is an adverse event that occurs due to medical error. Negligent adverse
      events are a subset of preventable adverse events where the care provided did not
      meet the standard of care expected of that practitioner. The study of improving
      the delivery of safe care for our patients is a rapidly growing field. Important
      components for development of programmes to improve the safety of patients
      include the leadership for the programme, the implementation of process design
      based on human limitations, the promotion of teamwork and function, the
      anticipation of unexpected events, and the creation of a learning environment.
      Much is yet to be learned about the risk and incidence of adverse events during
      hospitalization of children with congenital cardiac disease. Errors due to human
      factors, such as poor communication, poor coordination, and suboptimal team work,
      have shown to be important causes of adverse outcomes in children undergoing
      cardiac surgery, and should be a focus for improvement. Future research on
      evaluating causes and prevention of medical errors and adverse events in this
      population at high risk, and consuming high resources, is essential. Issues of
      inadequate safeguards for patients have been prominent in the media, and have
      been highlighted in reports from the Institute of Medicine. Our review discusses
      research on the causes of medical error, and proposes concepts to design
      successful programmes to improve safety for the patients on a local level.

PMID- 18039405
TI  - Cardiopulmonary resuscitation: special considerations for infants and children
      with cardiac disease.
AB  - Pulseless cardiac arrest, defined as the cessation of cardiac mechanical
      activity, determined by unresponsiveness, apneoa, and the absence of a palpable
      central pulse, accounts for around one-twentieth of admissions to paediatric
      intensive care units, be they medical or exclusively cardiac. Such cardiac arrest
      is higher in children admitted to a cardiac as opposed to a paediatric intensive
      care unit, but the outcome of these patients is better, with just over two-fifths
      surviving when treated in the cardiac intensive care unit, versus between one
      sixth and one-quarter of those admitted to paediatric intensive care units.
      Children who receive chest compressions for bradycardia with pulses have a
      significantly higher rate of survival to discharge, at 60%, than do those
      presenting with pulseless cardiac arrest, with only 27% surviving to discharge.
      This suggests that early resuscitation before the patient becomes pulseless,
      along with early recognition and intervention, are likely to improve outcomes.
      Recently published reports of in-hospital cardiac arrests in children can be
      derived from the multi-centric National Registry of Cardiopulmonary Resuscitation
      provided by the American Heart Association. The population is heterogeneous, but
      most arrests occurred in children with progressive respiratory insufficiency,
      and/or progressive circulatory shock. During the past 4 years at the Children's
      Hospital of Philadelphia, 3.1% of the average 1000 annual admissions to the
      cardiac intensive care unit have received cardiopulmonary resuscitation. Overall
      survival of those receiving cardiopulmonary resuscitation was 46%. Survival was
      better for those receiving cardiopulmonary resuscitation after cardiac surgery,
      at 53%, compared with survival of 33% for pre-operative or non-surgical patients
      undergoing resuscitation. Clearly there is room for improvement in outcomes from
      cardiac resuscitation in children with cardiac disease. In this review,
      therefore, we summarize the newest developments in paediatric resuscitation, with
      an expanded focus upon the unique challenges and importance of anticipatory care
      in infants and children with cardiac disease.

PMID- 18039407
TI  - Managing the demands of professional life.
AB  - Our review summarizes the thoughts we shared in presenting the 8th annual Daicoff
      lecture. It is fitting, therefore, to begin with a few comments about George
      Daicoff. One of us (RU) first met George at a meeting, which might have been the
      Southern Thoracic Surgical Association. He was very kind and gracious, and made
      me feel welcome. We would like for each of you now reading this review to think,
      for a moment, of when you have had an experience like that from someone you
      didn't know well, and how it made you feel comfortable, and that maybe you "fit
      in." George, we thank you for that memory. Our field needs more graciousness. As
      all of us function in our everyday world, we should remember that we never know
      when our acts of graciousness one to another will be remembered and acknowledged.
      Our review summarises five concepts that we have found helpful in our work with
      similar groups of busy professionals. The first is mindfulness, sometimes
      referred to as being conscious of the present moment. It is an irony of the
      training of health care professionals that we are constantly being directed
      towards a future focus. We readily don the blinders of a professional life that
      keeps us focusing on what lies ahead. Although some element of this is essential
      for professional success, we run the risk of missing out on the richness of our
      everyday experiences. The second is intentionality. In our work with busy
      professionals, we have found that so many have drifted into the automaticity of
      patterned responses. This gets us in so much trouble because we forget that we
      always have choice. The third is mindsight. This is about empathy, and the
      ability to connect to the experiences of others. Mindsight is about connecting to
      our differences. The fourth is forgiveness and shared meanings. It is important
      to practice forgiveness, and to create shared meanings in relationships. These
      processes allow us to reconnect to people who have hurt, disappointed, or angered
      us. When we don't forgive, we create toxic relationships, both with ourselves and
      with others. It is the heaviness of resentment that prevents us from being at
      ease. The final concept concerns management of stress. We should learn to
      recognize when we are stressed. We cannot manage what we don't know. It is our
      belief that attention to these features will help you better manage the numerous
      demands of your life.

PMID- 18039408
TI  - Analysis of outcomes for congenital cardiac disease: can we do better?
AB  - This review discusses the historical aspects, current state of the art, and
      potential future advances in the areas of nomenclature and databases for the
      analysis of outcomes of treatments for patients with congenitally malformed
      hearts. We will consider the current state of analysis of outcomes, lay out some
      principles which might make it possible to achieve life-long monitoring and
      follow-up using our databases, and describe the next steps those involved in the
      care of these patients need to take in order to achieve these objectives. In
      order to perform meaningful multi-institutional analyses, we suggest that any
      database must incorporate the following six essential elements: use of a common
      language and nomenclature, use of an established uniform core dataset for
      collection of information, incorporation of a mechanism of evaluating case
      complexity, availability of a mechanism to assure and verify the completeness and
      accuracy of the data collected, collaboration between medical and surgical
      subspecialties, and standardised protocols for life-long follow-up. During the
      1990s, both The European Association for Cardio-Thoracic Surgery and The Society
      of Thoracic Surgeons created databases to assess the outcomes of congenital
      cardiac surgery. Beginning in 1998, these two organizations collaborated to
      create the International Congenital Heart Surgery Nomenclature and Database
      Project. By 2000, a common nomenclature, along with a common core minimal
      dataset, were adopted by The European Association for Cardio-Thoracic Surgery and
      The Society of Thoracic Surgeons, and published in the Annals of Thoracic
      Surgery. In 2000, The International Nomenclature Committee for Pediatric and
      Congenital Heart Disease was established. This committee eventually evolved into
      the International Society for Nomenclature of Paediatric and Congenital Heart
      Disease. The working component of this international nomenclature society has
      been The International Working Group for Mapping and Coding of Nomenclatures for
      Paediatric and Congenital Heart Disease, also known as the Nomenclature Working
      Group. By 2005, the Nomenclature Working Group crossmapped 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 with the European Paediatric Cardiac Code of the Association for
      European Paediatric Cardiology, and therefore created the International
      Paediatric and Congenital Cardiac Code, which is available for free download from
      the internet at [http://www.IPCCC.NET]. This common nomenclature, the
      International Paediatric and Congenital Cardiac Code, and the common minimum
      database data set created by the International Congenital Heart Surgery
      Nomenclature and Database Project, are now utilized by both The European
      Association for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons.
      Between 1998 and 2007 inclusive, this nomenclature and database was used by both
      these two organizations to analyze outcomes of over 100,000 patients undergoing
      surgical treatment for congenital cardiac disease. Two major multi-institutional
      efforts that have attempted to measure the complexity of congenital heart surgery
      are the Risk Adjustment in Congenital Heart Surgery-1 system, and the Aristotle
      Complexity Score. Current efforts to unify the Risk Adjustment in Congenital
      Heart Surgery-1 system and the Aristotle Complexity Score are in their early
      stages, but encouraging. Collaborative efforts involving The European Association
      for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons are under way to
      develop mechanisms to verify the completeness and accuracy of the data in the
      databases. Under the leadership of The MultiSocietal Database Committee for
      Pediatric and Congenital Heart Disease, further collaborative efforts are ongoing
      between paediatric and congenital cardiac surgeons and other subspecialties,
      including paediatric cardiac anaesthesiologists, via The Congenital Cardiac
      Anesthesia Society, paediatric cardiac intensivists, via The Pediatric Cardiac
      Intensive Care Society, and paediatric cardiologists, via the Joint Council on
      Congenital Heart Disease and The Association for European Paediatric Cardiology.
      In finalising our review, we emphasise that analysis of outcomes must move beyond
      mortality, and encompass longer term follow-up, including cardiac and non cardiac
      morbidities, and importantly, those morbidities impacting health related quality
      of life. Methodologies must be implemented in these databases to allow uniform,
      protocol driven, and meaningful, long term follow-up.

PMID- 18039409
TI  - The influence of Plato, Aristotle, and the ancient Polis on a programme for
      congenital cardiac surgery: the virtuous partnership.
AB  - The problems that exist in maintaining a partnership in paediatric cardiac
      surgery are considerable. They relate to fairness in allocation of time for
      leisure, the apportioning of cases between the partners, internal competition
      between them, financial considerations, and promotion of the ego. In this review,
      we discuss our own experiences in maintaining a partnership over a period of more
      than 18 years, relating such a "virtuous partnership" to the writings of Plato
      and Aristotle, and setting it against the tenets of the ancient Greek polis. The
      polis, or city state, came to prominence in ancient Greece during the golden age
      of Pericles, this period seeing the initial evolution of Western philosophy, as
      well as numerous other scientific, artistic and architectural advances. The
      concept of the polis was to create a natural association with its citizens that
      nurtured all that is best in people, at the same time defining their character.
      In this respect, according to Plato, the person and the polis are mirror images.
      Aristotle then expanded this notion to incorporate the various forms of
      friendship, which he pointed out last only as long as the interrelated pleasure
      survives. Using these principles as the point of departure, we argue that cardiac
      surgeons should respect moral virtue in each other. Extending this process means
      that we should also respect, and celebrate, our relationships with affiliated
      physicians, nurses, perfusionists, administrators, and all concerned in the care
      of children with congenitally malformed hearts. In this way, we create a virtuous
      partnership for congenital cardiac surgery that promotes all that was good, as
      engendered in the ancient Greek polis. As we extend these observations to the
      modern world, we discuss some of the features that have permitted us to work so
      well together. One of the most important is a summoning and unwritten tenet that
      greets us as we enter the operating room, namely "check your ego at the door".
      The operative choice should always be dictated by discussion, citations of
      literature, considered opinions, and relevance to the particular patient.
      Continuity of care should lead inexorably to the paediatric intensive care unit,
      where collegial relationships should be maintained with all those working
      therein. We need to recognize that there are various "captains of the ship", who
      must work in harmony so as to bring the best possible care to our patients. We
      always endeavour to empower others to act on our behalf, based on their
      experience and training. Whether we have achieved our desired moral excellence,
      and produced the completed or perfected friendship, is for others to judge. From
      our stance, we believe we have created a favourable environment by hard work,
      unselfish attitudes, and celebration of our mutual accomplishments. We were not
      the first to forge this kind of professional association, and happily we will not
      be the last.

PMID- 18039410
TI  - Mentorship, learning curves, and balance.
AB  - Professionals working in the arena of health care face a variety of challenges as
      their careers evolve and develop. In this review, we analyze the role of
      mentorship, learning curves, and balance in overcoming challenges that all such
      professionals are likely to encounter. These challenges can exist both in
      professional and personal life. As any professional involved in health care
      matures, complex professional skills must be mastered, and new professional
      skills must be acquired. These skills are both technical and judgmental. In most
      circumstances, these skills must be learned. In 2007, despite the continued need
      for obtaining new knowledge and learning new skills, the professional and public
      tolerance for a "learning curve" is much less than in previous decades.
      Mentorship is the key to success in these endeavours. The success of mentorship
      is two-sided, with responsibilities for both the mentor and the mentee. The
      benefits of this relationship must be bidirectional. It is the responsibility of
      both the student and the mentor to assure this bidirectional exchange of benefit.
      This relationship requires time, patience, dedication, and to some degree
      selflessness. This mentorship will ultimately be the best tool for mastering
      complex professional skills and maturing through various learning curves.
      Professional mentorship also requires that mentors identify and explicitly teach
      their mentees the relational skills and abilities inherent in learning the
      management of the triad of self, relationships with others, and professional
      responsibilities.Up to two decades ago, a learning curve was tolerated, and even
      expected, while professionals involved in healthcare developed the techniques
      that allowed for the treatment of previously untreatable diseases. Outcomes have
      now improved to the point that this type of learning curve is no longer
      acceptable to the public. Still, professionals must learn to perform and develop
      independence and confidence. The responsibility to meet this challenge without a
      painful learning curve belongs to both the younger professionals, who must
      progress through the learning curve, and the more mature professionals who must
      create an appropriate environment for learning. In addition to mentorship, the
      detailed tracking of outcomes is an essential tool for mastering any learning
      curve. It is crucial to utilize a detailed database to track outcomes, to learn,
      and to protect both yourself and your patients. It is our professional
      responsibility to engage in self-evaluation, in part employing voluntary sharing
      of data. For cardiac surgical subspecialties, the databases now existing for The
      European Association for CardioThoracic Surgery and The Society of Thoracic
      Surgeons represent the ideal tool for monitoring outcomes. Evolving initiatives
      in the fields of paediatric cardiology, paediatric critical care, and paediatric
      cardiac anaesthesia will play similar roles.A variety of professional and
      personal challenges must be met by all those working in health care. The
      acquisition of learned skills, and the use of special tools, will facilitate the
      process of conquering these challenges. Choosing appropriate role models and
      mentors can help progression through any learning curve in a controlled and
      protected fashion. Professional and personal satisfaction are both necessities.
      Finding the satisfactory balance between work and home life is difficult, but
      possible with the right tools, organization skills, and support system at work
      and at home. The concepts of mentorship, learning curves and balance cannot be
      underappreciated.

PMID- 18039411
TI  - Assessment of nutritional profiles: a novel system based on a comprehensive
      approach.
AB  - The prevalence of non-communicable diseases (for example, cardiovascular
      disorders, type 2 diabetes and cancer) is rampant in Western societies,
      accounting for approximately 60 % of all causes of death. A large proportion of
      non-communicable diseases can be prevented through appropriate diets and
      lifestyles. Accordingly, several health authorities and regulatory bodies are
      assessing the nutritional profiles of food items and whole diets, to implement
      guidelines aimed at improving the diet of the general population. While a global
      approach is desirable, the need of individuals to maintain their distinct dietary
      habits must also be taken into account. The portion sizes of food as well as
      pattern of food consumption, for example during or between the main meals, are
      very important in determining the nutritional profile of a diet. A novel method
      to assess the nutritional profile of foods is being proposed and made available
      on-line. Its main innovative aspects are (1) the comprehensive manner with which
      the system analyses and computes a great range of features of individual food
      items and (2) the distinction among eating occasions, namely during or in-between
      the main meals. Moreover, this approach allows for rapid modification and great
      flexibility to suit individual needs and gastronomic habits.

PMID- 18039412
TI  - UK Food Standards Agency Workshop Report: the effects of the dietary n-6:n-3
      fatty acid ratio on cardiovascular health.
AB  - This report summarises a workshop convened by the UK Food Standards Agency (FSA)
      on 11 September 2006 to review the results of three FSA-funded studies and other
      recent research on effects of the dietary n-6:n-3 fatty acid ratio on
      cardiovascular health. The objective of this workshop was to reach a clear
      conclusion on whether or not it was worth funding any further research in this
      area. On the basis of this review of the experimental evidence and on theoretical
      grounds, it was concluded that the n-6:n-3 fatty acid ratio is not a useful
      concept and that it distracts attention away from increasing absolute intakes of
      long-chain n-3 fatty acids which have been shown to have beneficial effects on
      cardiovascular health. Other markers of fatty acid intake, that more closely
      relate to physiological function, may be more useful.

PMID- 18039413
TI  - Electron microscopic observation of cytoskeletal frame structures and detection
      of tubulin on the apical region of Cryptosporidium parvum sporozoites.
AB  - Cryptosporidium parvum is an intracellular protozoan parasite belonging to the
      phylum Apicomplexa, and a major cause of waterborne gastroenteritis throughout
      the world. Invasive zoites of apicomplexan parasites, including C. parvum, are
      thought to have characteristic organelles on the apical apex; however, compared
      with other parasites, the cytoskeletal ultrastructure of C. parvum zoites is
      poorly understood. Thus, in the present study, we ultrastructurally examined C.
      parvum sporozoites using electron microscopy to clarify the framework of invasive
      stages. Consequently, at the apical end of sporozoites, 3 apical rings and an
      electron-dense collar were seen. Two thick central microtubules were seen further
      inside sporozoites and extended to the posterior region. Using anti-alpha and 
      beta tubulin antibodies generated from sea urchin and rat brain, both antibodies
      cross-reacted at the apical region of sporozoites in immunofluorescent
      morphology. The molecular mass of C. parvum alpha tubulin antigen was 50 kDa by
      Western blotting and the observed apical cytoskeletal structures were shown to be
      composed of alpha tubulin by immunoelectron microscopy. These results suggested
      that C. parvum sporozoites were clearly different in their cytoskeletal structure
      from those of other apicomplexan parasites.

PMID- 18039414
TI  - Infection of red foxes with Echinococcus multilocularis in western Switzerland.
AB  - In the Jura mountains, Plateau and Alps of western Switzerland important
      variations in the prevalence of Echinococcus multilocularis infection in red
      foxes were observed between geographical areas from 1990 to 1995. The Jura
      mountains and the Plateau had higher mean prevalence levels than the Alps with
      30.6, 32.4 and 18.8%, respectively. The highest rate was recorded in the Plateau
      in the canton of Fribourg with a prevalence of 52.3%. The prevalence of E.
      multilocularis infection in foxes in the alpine canton of Valais was the lowest
      (7.1%). Juvenile foxes were found to be more susceptible to E. multilocularis
      than adults. Adult foxes were less heavily infected in summer and autumn, while
      the prevalence in juveniles (less than 1 year old) increased between the spring
      and winter, when they are more than 6 months old. The retrospective data relate
      to the beginning of the 1990s, since when a drastic prevalence increase of E.
      multilocularis infection in foxes has occurred in several regions of Europe.
      Nevertheless, the study is a major contribution to the epidemiological situation
      of E. multilocularis in central Europe, in that it contains valuable information
      on spatial distribution and seasonal differences in different age groups of
      foxes.

PMID- 18039415
TI  - Nerve origin of vestibular schwannoma: a prospective study.
AB  - OBJECTIVE: The origin of vestibular schwannoma has always been a matter of
      debate. The aim of our study was to identify the nerve origin of this tumour.
      STUDY DESIGN: Prospective case review. This study was conducted at Gruppo
      Otologico, a private referral centre for neurotology and skull base surgery.
      METHODS: A total of 200 cases of vestibular schwannoma were included in the
      study. All the tumours were removed surgically utilising the translabyrinthine
      approach. The origin of the tumour was sought at the fundus of the internal
      auditory canal. RESULTS: A total of 200 consecutive cases was included in the
      study. The origin of the tumour was limited to one nerve at the fundus in 152
      cases (76 per cent). Out of these cases, the tumour originated from the inferior
      vestibular nerve in 139 cases (91.4 per cent), from the superior vestibular nerve
      in nine cases (6 per cent), from the cochlear nerve in two cases (1.3 per cent)
      and from the facial nerve in two cases (1.3 per cent). CONCLUSION: The vast
      majority of vestibular schwannomas originate from the inferior vestibular nerve;
      the incidence of involvement of this nerve increases as the tumour size
      increases. An origin of vestibular schwannoma from the inferior vestibular nerve
      can be considered as one of the explanatory factors for the poor functional
      outcome of the extended middle cranial fossa approach, and probably accounts also
      for the better hearing preservation rate reported in some series for the
      retrosigmoid approach.

PMID- 18039416
TI  - Management of Meniere's disease in general practice: adherence to the UK National
      Health Service 'Prodigy' guidelines.
AB  - INTRODUCTION: Dizziness is a common presenting complaint in primary healthcare.
      One differential diagnosis is Meniere's disease. The UK National Health Service
      'Prodigy' guidelines have been produced to help healthcare professionals to
      diagnose and manage Meniere's disease. The aim of this audit was to consider how
      Meniere's disease is managed in general practice, and to assess how well general
      practitioners adhere to the Prodigy guidelines. MATERIALS AND METHODS: We
      identified general practices near the Torbay region of south Devon which had a
      'TQ' postcode. There were 41 practices, staffed by a total of 203 general
      practitioners. We wrote to each general practitioner, asking them to fill in a
      questionnaire regarding Meniere's disease. Our practice response rate was 68 per
      cent and our individual rate 43 per cent. RESULTS: The mean correct answer rate
      was >50 per cent. The respondents achieved this despite few being aware of any
      formal guidelines, and none being aware of the Prodigy guidelines. CONCLUSION:
      Detailed knowledge of Meniere's disease was uncommon, and formal guidelines were
      not frequently consulted.

PMID- 18039417
TI  - Endoscopic dacryocystorhinostomy in functional lacrimal obstruction.
AB  - INTRODUCTION: We performed endoscopic dacryocystorhinostomy in cases diagnosed
      with both anatomical and functional lacrimal obstruction, and here report results
      for the latter cases. METHODS: Sixty-eight endoscopic dacryocystorhinostomies
      were performed for functional obstruction on 44 patients. The indication for
      surgery was epiphora in 66 patients and recurrent dacryocystitis in two. The
      minimum follow up was six months. RESULTS: There was complete cure in 44 (65 per
      cent) patients, partial cure in nine (13 per cent) and no improvement in 15 (22
      per cent). Revision surgery was performed in five of the 15 cases with no
      improvement, after which there was an overall complete cure in 47 patients (69
      per cent), partial cure in 10 (15 per cent) and no improvement in 11 (16 per
      cent). DISCUSSION: Endoscopic dacryocystorhinostomy is indicated in cases of
      epiphora with a diagnosis of functional lacrimal obstruction. Currently available
      investigations cannot reliably distinguish partial anatomical obstruction from
      pump failure.

PMID- 18039418
TI  - Changing trends in bacteriology of peritonsillar abscess.
AB  - OBJECTIVES: To evaluate the type of aerobic bacteria commonly isolated from
      peritonsillar abscesses. STUDY DESIGN: A retrospective study involving 60
      patients presenting with peritonsillar abscess treated between 2003 and 2006.
      SETTING: The patients were treated in a tertiary care, teaching hospital. The
      records of the patients were reviewed and analysed. RESULTS: Gram-positive
      organisms were commonly isolated from the abscesses. However, an increasing trend
      towards Gram-negative bacterial isolates was noted. The antibiogram showed
      changing patterns of sensitivity, with a resistance to penicillin. CONCLUSION:
      There is an increasing incidence of Gram-negative aerobic bacteria causing
      peritonsillar abscess. Appropriate antibiotics for Gram-negative bacteria should
      be included in the regimen if such bacteria are isolated in culture and
      sensitivity studies. SIGNIFICANCE: Empirical antibiotics with Gram-negative cover
      will be appropriate as adjunctive therapy.

PMID- 18039419
TI  - Functional vocal results after CO2 laser endoscopic surgery for glottic tumours.
AB  - INTRODUCTION: Vocal results after endoscopic cordectomy have not yet been well
      defined. The aim of this study was to assess the vocal function of patients who
      had undergone CO2 laser cordectomy. DESIGN: Retrospective, observational and
      control group study, conducted in a tertiary care medical department. METHODS:
      One hundred and thirty-five male patients (age range 36-83 years) underwent
      different types of endoscopic cordectomy. Forty age-matched, euphonic male
      subjects were selected as controls. Patients were classified according to the
      main site of the phonatory neo-glottis. Outcome measures were maximum phonation
      time, vocal intensity and harmonic/noise ratio. Mann-Whitney and rank Spearman
      tests were used for statistical analysis. RESULTS: Findings indicated
      statistically significant differences for all parameters, comparing patients and
      controls (p<0.001), and a direct positive relation between type of functional
      compensation and outcome measures in the study patients (p<0.001). CONCLUSIONS:
      The results indicate that functional compensation and outcome measures were
      related, and that no functional compensation enabled the study patients to
      achieve a voice quality comparable with that of controls.

PMID- 18039420
TI  - The superosmic phenomenon.
AB  - BACKGROUND: Olfaction studies in the institution of Department of
      Otorhinolaryngology at Leicester Royal Infirmary have detected a previously
      unreported, variable phenomenon--'superosmia'--in which subjects' olfaction
      threshold concentrations are up to 100,000 smaller than the average value.
      OBJECTIVES: The aim of this report is to define and quantify this phenomenon.
      METHODS: Two hundred and thirty subjects, who had been screened for active nasal
      pathology (age range 20-60 years), underwent individual olfactory threshold tests
      for phenylethyl alcohol or eucalyptol, using a computer-driven olfactometer in a
      controlled laboratory setting. Some tests were single tests and others were
      repeated on a small cohort. RESULTS: Two per cent of subjects demonstrated the
      superosmic phenomenon on single testing, and 10 per cent demonstrated this
      phenomenon on variable occasions during repeated testing. The superosmic
      phenomenon was defined by: (1) confident olfactory perception of a threshold at
      least equal to if not greater than three threshold levels below the subject's
      average threshold; (2) repeated perception of the odour at this level for at
      least 10 responses (1:1024 probability of chance finding); and (3) (where time
      permitted) a sudden, rapid loss of superosmia. CONCLUSIONS: Superosmia is a
      distinct phenomenon, the stimulus or mechanism of which is currently the subject
      of further research. The enhancement of olfactory ability may be possible through
      activation of an accessory pathway or modulation of the existing olfactory
      apparatus.

PMID- 18039421
TI  - Molecular prognostic markers in locally advanced colon cancer.
AB  - For patients who undergo successful surgery for colon cancer, additional
      chemotherapy is recommended in high-risk stage II and stage III disease.
      Colorectal cancer prognosis is stage and grade dependent, and many tumors with
      similar histopathologic features show significantly different clinical outcomes.
      Therefore, tumor recurrence after curative resection continues to be a
      significant problem in the management of colon cancer, and approximately 50% of
      patients will develop recurrent disease. There are a few clinical and potential
      molecular markers that can predict clinical outcome in locally advanced colon
      cancer. Accordingly, the development of molecular markers of prognosis is
      critical in making a tailored adjuvant treatment with molecular stratification
      possible. Many new biomarkers have been investigated; however, none of them have
      yet been validated in large prospective clinical trials. To date, the two most
      promising and most studied mechanisms of genomic instability are chromosomal
      instability with deletion of chromosome 18q and 17p and microsatellite
      instability (MSI). Eastern Cooperative Oncology Group 5202 is a prospective
      clinical trial which is randomizing patients with stage II disease based on their
      MSI and 18q status to observation versus adjuvant chemotherapy with the intention
      of prospectively determining their prognostic value as molecular markers. This
      review will discuss the most promising molecular prognostic markers and provide
      an update on the most recent developments.

PMID- 18039422
TI  - Role of tyrosine kinase inhibitors in the treatment of advanced colorectal
      cancer.
AB  - Colorectal cancer (CRC) is a common health problem in Western countries. In
      advanced disease, either FOLFOX (oxaliplatin/5-fluorouracil [5-FU]/leucovorin
      [LV]) or FOLFIRI (irinotecan/LV/5-FU) are accepted first-line chemotherapy
      regimens, but median survival appears to plateau with a chemotherapy-only
      approach. The use of epidermal growth factor receptor (EGFR)- and vascular
      endothelial growth factor (VEGF)-targeting monoclonal antibodies has increased
      the median survival of patients with advanced CRC beyond 20 months. However, the
      precise role of cetuximab, panitumumab and bevacizumab in combination with
      different chemotherapeutic regimens is still being determined in first- and
      second-line settings. The activity and tolerance of the EGFR tyrosine kinase
      inhibitors (TKIs), gefitinib erlotinib, and EKB-569, alone or in combination with
      chemotherapy, have been explored in patients with metastatic CRC. Regarding VEGF
      receptor TKIs, 2 phase III clinical trials determined the role of vatalanib in
      combination with FOLFOX. Efficacy of the oral multitargeted TKIs sorafenib and
      sunitinib is under investigation. This article aims to review the role of TKIs in
      advanced CRC.

PMID- 18039423
TI  - A systematic review of the use of quality of life measures in colorectal cancer
      research with attention to outcomes in elderly patients.
AB  - PURPOSE: Quality of life (QOL) measures are critical to the evaluation of new
      cancer treatments, particularly for elderly patients. Our intent was to assess
      patterns of use of QOL endpoints in colorectal cancer (CRC) treatment research
      and to summarize current knowledge about how CRC treatment affects elderly
      patients. PATIENTS AND METHODS: We searched MEDLINE for English-language, human
      trials published from 1995 to 2005 that met the following criteria: reported on
      patients with CRC, were not surgery-only cohorts, and included a QOL or
      functional endpoints. Trials specifically reporting data on elderly patients were
      reviewed in depth and summarized. RESULTS: One hundred twenty-one eligible
      studies and 10 trials with elderly-specific data were found. The median number of
      trials published annually increased from 5 (range, 4-8 trials) between 1995 and
      1999 to 14.5 (range, 11-22 trials) between 2000 and 2005. Chemotherapy was the
      most commonly studied treatment (55%), and metastatic CRC (55%) was the most
      commonly studied population. The European Organization for Research and Treatment
      of Cancer C30, with or without C38, was the most frequently used instrument
      (49%). Studies reporting on elderly patients showed that many patients experience
      a decline in physical function immediately after surgery and have increased need
      for supportive services. Little information is available on the effect of
      chemotherapy in elderly patients. Use of QOL and functional measures in treatment
      related CRC research has increased; however, it continues to be hampered by a
      lack of dissemination and methodologic problems. CONCLUSION: Missing data from
      patient attrition, limitations of assessment methods, and a small number of
      patients treated with chemotherapy in the trials reporting on elderly patients
      seriously limit our ability to draw conclusions from this survey about how
      treatment affects QOL or function in CRC.

PMID- 18039424
TI  - Safety and efficacy of first-line chemotherapy in unresected metastatic
      colorectal cancer.
AB  - BACKGROUND: Primary tumor resection in patients with metastatic colorectal cancer
      is considered highly controversial. Historical data suggest a low risk of primary
      tumor-related complications in patients treated with first-line 5-fluorouracil (5
      FU) chemotherapy. However, there are very limited data on the safety and efficacy
      of first-line combination chemotherapy in this unresected-primary population,
      especially in the setting of rectal cancer. PATIENTS AND METHODS: We performed a
      single-institution retrospective study to evaluate the primary tumor-related
      complication rate and outcome of patients with unresected metastatic colorectal
      cancer treated with first-line chemotherapy. Estimation of the overall and
      progression-free survival distributions were done using the Kaplan-Meier method.
      RESULTS: Thirty-eight patients were identified: 26 had primary colon cancers and
      12 had primary rectal cancers. Thirty-one patients were treated with first-line
      FOLFOX (oxaliplatin/leucovorin/5-FU) with or without bevacizumab. In patients
      with colon tumors, only 2 (7%) required surgery, both for obstruction. In
      patients with rectal tumors, 3 (25%) developed progressive obstructive symptoms,
      and 2 developed worsening pain. Four of these patients were adequately palliated
      with chemoradiation; only 1 patient required a diverting colostomy. The median
      progression-free survival was 7 months, and overall survival was 17.3 months.
      Twenty-two patients died because of disease progression, only 3 of whom developed
      obstructive symptoms at the primary tumor site before death. CONCLUSION: First
      line chemotherapy is feasible and safe in patients with unresected colon and
      nonirradiated rectal cancer. The rate of bowel obstruction requiring surgical
      intervention in this population was < 10%. These results support an approach that
      defers surgery in non-obstructed, noncurable patients in favor of systemic
      chemotherapy as initial treatment.

PMID- 18039425
TI  - Intensity-modulated radiation therapy for the treatment of anal cancer.
AB  - PURPOSE: The aim of this study was to assess whether intensity-modulated
      radiation therapy (RT; IMRT) can reduce dose to normal tissues (organs at risk)
      while maintaining equivalent target coverage. PATIENTS AND METHODS: A 9-field,
      non-coplanar, 1-cm beamlet IMRT plan was designed for 9 patients who were
      previously treated for anal cancer with conventional field arrangements. Clinical
      target volumes and organs at risk (OARs) were defined. Target coverage was
      assigned highest priority for optimization, followed sequentially by organ at
      risk. The genitalia and perineal skin were the highest priority OARs.
      Lexicographic ordering-based IMRT optimization was used to generate a conformal
      plan, which was compared with the conventional, previously delivered RT plan.
      RESULTS: The IMRT and conventional RT plan achieved homogeneous dose coverage of
      all target volumes. Intensity-modulated RT produced highly conformal dose
      distributions compared with conventional techniques, with avoidance of critical
      normal structures. Statistically significant reductions in mean doses to the
      perineal skin and to the genitalia were seen with IMRT, with only a modest
      increase in mean dose to the bony pelvis. CONCLUSION: Intensity-modulated RT,
      with lexicographic ordering, allows for substantial reduction of dose to OARs
      while maintaining adequate target coverage. These encouraging findings might
      translate into reductions of treatment-related toxicity, gains in local control,
      or improvements in quality of life.

PMID- 18039426
TI  - Colorectal carcinomas with microsatellite instability display increased
      thymidylate synthase gene expression levels.
AB  - BACKGROUND: This study investigated whether patients with colorectal cancer (CRC)
      who have tumors with high microsatellite instability (MSI; MSI-H) had an altered
      expression of the folate and methyl-group metabolism. The gene expression levels
      of thymidylate synthase (TS), reduced folate carrier (RFC-1), folylpolyglutamate
      synthase (FPGS), and methylenetetrahydrofolate reductase (MTHFR) in mucosa and
      tumor were compared with patients with MSS. Furthermore, the influence of TS
      polymorphisms on TS gene expression levels and MSI-H was studied. PATIENTS AND
      METHODS: The microsatellite status (MSI-H, low instability [MSI-L], or stable
      [MSS]) and TS polymorphisms were analyzed in genomic DNA from 181 patients with
      CRC. Gene expression levels of TS, RFC-1, FPGS, and MTHFR in mucosa and tumors
      were quantified and the difference in TS expression between tumor and mucosa was
      designated DeltaTS. RESULTS: Significantly higher gene expression levels of TS (P
      < .0001) were detected in patients with CRC with MSI-H compared with MSS/MSI-L
      tumors. Gene expression of TS and FPGS were significantly higher in right-sided
      MSI-H tumors compared with right-sided MSS/MSI-L tumors (P < .0001, P = .041,
      respectively). A significant correlation between DeltaTS and the number of
      unstable markers was found (P < .0001). An inverse association between age and TS
      expression was found in MSI tumors (r = -0.57; P = .0004) and also in right-sided
      tumors (r = -0.25, P = .011) regardless of MSI status. No relation was detected
      between MSI status and the TS polymorphisms or between the TS polymorphisms and
      TS expression. CONCLUSION: This study has revealed, for the first time, that age
      and the frequency of unstable MSI markers were factors that were linked to the
      variability in TS gene expression in tumors.

PMID- 18039427
TI  - Atypical cutaneous lymphoid hyperplasia induced by chemotherapy in a patient with
      advanced colon carcinoma.
AB  - Some conditions are predisposed to excessive lymphocyte responses, which can
      progress to a benign condition, ie, atypical cutaneous lymphoid hyperplasia
      (ACLH), or a malignant lymphoma. Clinical diagnosis of drug-associated
      pseudolymphoma can be based on a temporal association between drug ingestion and
      lesion onset followed by resolution without recurrence after discontinuation of
      drug administration. Herein, we report the case of a 66-year-old man with
      advanced colon carcinoma with ACLH developed while receiving chemotherapy regimen
      with oxaliplatin/5-fluorouracil/leucovorin. The authors postulate that
      chemotherapy can promote an aberrant immune response to an antigen that can be
      the drug itself or other self-antigens.

PMID- 18039428
TI  - Anticipated regret as an additional predictor in the theory of planned behaviour:
      a meta-analysis.
AB  - This paper details the results of a meta-analysis incorporating all the
      appropriately augmented TPB studies in order to statistically determine the
      additive effects of anticipated regret (AR) both to the prediction of intentions
      after the TPB variables and to the direct impacts on behaviour. Over a number of
      studies there was a strong AR-intention relationship (r(+)=.47, k=25, N=11,254),
      and AR significantly and independently added to the prediction of intentions over
      and above the TPB variables; there was a moderate relationship between AR and
      behaviour (r(+)=.28, k=8, N=2,035) with AR having a direct and significant impact
      on prospective behaviour, and there was support for the unique contribution of AR
      even when accounting for attitude. Implications and issues for further research
      are discussed.

PMID- 18039429
TI  - Stressful life-events exposure is associated with 17-year mortality, but it is
      health-related events that prove predictive.
AB  - OBJECTIVES: Despite the widely-held view that psychological stress is a major
      cause of poor health, few studies have examined the relationship between
      stressful life-events exposure and death. The present analyses examined the
      association between overall life-events stress load, health-related and health
      unrelated stress, and subsequent all-cause mortality. DESIGN: This study employed
      a prospective longitudinal design incorporating time-varying covariates. METHODS:
      Participants were 968 Scottish men and women who were 56 years old. Stressful
      life-events experience for the preceding 2 years was assessed at baseline, 8-9
      years and 12-13 years later. Mortality was tracked for the subsequent 17 years
      during which time 266 participants had died. Cox's regression models with time
      varying covariates were applied. We adjusted for sex, occupational status,
      smoking, BMI, and systolic blood pressure. RESULTS: Overall life-events numbers
      and their impact scores at the time of exposure and the time of assessment were
      associated with 17-year mortality. Health-related event numbers and impact scores
      were strongly predictive of mortality. This was not the case for health-unrelated
      events. CONCLUSIONS: The frequency of life-events and the stress load they
      imposed were associated with all-cause mortality. However, it was the experience
      and impact of health-related, not health-unrelated, events that proved
      predictive. This reinforces the need to disaggregate these two classes of
      exposures in studies of stress and health outcomes.

PMID- 18039430
TI  - Validation of a Chinese achievement goal orientation questionnaire.
AB  - BACKGROUND: The mixed findings of previous studies on the nature and effects of
      performance goals have led to a call for re-examination of the dichotomous
      framework of achievement goal orientation theory. While the call for a revised
      achievement goal orientation theory has received considerable discussion in
      Western studies, it is not clear whether the revised theory can also be applied
      in other ethnic and cultural contexts. AIMS: Our aim was to validate the Chinese
      version of Elliot and Church's (1007) Goal Orientation Questionnaire and to
      initially test the revised goal orientation theory in the context of Chinese
      students in Hong Kong. SAMPLE: A total of 270 Chinese students (137 boys and 133
      girls) from a primary and secondary school in Hong Kong participated in Study 1.
      Study 2 involved a total of 9,440 students (5,420 boys and 4,020 girls) from 10
      primary and 18 secondary schools in Hong Kong. METHOD: Participants in Study 1
      completed a Chinese Goal Orientation Questionnaire (CGOQ) measuring three types
      of goal orientation. Exploratory factor analysis, item-total correlation, and
      reliability analyses were undertaken to assess the psychometric quality of the
      CGOQ. In Study 2, confirmatory factor analysis was used to provide further
      validation for the revised questionnaire. The relationships among different goal
      orientations and that with students' perceived classroom environment and self
      efficacy were also explored using structural equation modelling. RESULTS:
      Findings of exploratory factor analysis in Study 1 and confirmatory factor
      analysis in Study 2 supported the proposed factor structure of the CGOQ. All the
      subscales in the questionnaire also showed good internal consistency
      reliabilities. The construct validity of the CGOQ was supported by its
      significant relationship with criterion measures. While most of the relationships
      between the three types of goal orientation and the learning-related variables
      measured in our study were consistent with the revised goal orientation theory,
      the positive relationships between performance-avoidance goals, mastery goals,
      and perceived classroom environment were different from previous studies.
      CONCLUSION: Our findings generally supported the trichotomous framework of the
      revised goal orientation theory with Chinese students in Hong Kong. Consistent
      with the revised goal orientation theory, our findings indicated that both
      mastery and performance-approach goals had positive impacts on students'
      learning. However, the positive relationships between performance-avoidance
      goals, mastery goals, and perceived classroom environment were contradictory to
      the conceptualization of performance-avoidance goals in the revised theory.
      Cultural and social factors affecting Hong Kong students' goal orientations are
      discussed.

PMID- 18039431
TI  - An index-based short form of the WAIS-III with accompanying analysis of
      reliability and abnormality of differences.
AB  - OBJECTIVES: To develop an index-based, seven subtest, short form of the WAIS-III
      that offers the same comprehensive range of analytic methods available for the
      full-length version. DESIGN AND METHODS: Psychometric. RESULTS: The short-form
      indices had high reliability and criterion validity. Scores are expressed as
      index scores and as percentiles. Methods are provided that allow setting of
      confidence limits on scores, and analysis of the reliability and abnormality of
      index score differences. A computer program that automates scoring and implements
      all the analytical methods accompanies this paper and can be downloaded from the
      following web address: http://www.abdn.ac.uk/ approximately
      psy086/Dept/sf_wais3.htm. CONCLUSIONS: The short form will be useful when
      pressure of time or client fatigue precludes use of a full-length WAIS-III. The
      accompanying computer program scores and analyses an individual's performance on
      the short form instantaneously and minimizes the chance of clerical error.

PMID- 18039433
TI  - Oxycodone: a review of its use in the management of pain.
AB  - BACKGROUND: Oxycodone is a strong opioid that acts at mu- and kappa-opioid
      receptors. It has pharmacological actions similar to strong opioids, but with a
      specific pharmacologic profile and greater analgesic potency to morphine. The
      efficacy of oxycodone in managing neuropathic and somatic pain, both of malignant
      and non-malignant origin, has been established in a wide range of settings.
      SCOPE: This review aims to provide a comprehensive evaluation of oxycodone and
      its role within clinical settings in order to provide an evidence-based
      perspective on its use in the clinic. Literature searches using Medline, EMBASE
      and Cochrane Databases were used to compile data for review. The review provides
      information on the pharmacokinetics and pharmacodynamics of oxycodone and also
      profiles established clinical data in neuropathic and somatic pain as well as
      emerging data to support the use of oxycodone in visceral pain, which may be due
      to its interaction with kappa-opioid receptors. Oxycodone is available in a range
      of formulations for oral, intraspinal and parenteral administration. FINDINGS:
      The prolonged-release form of oxycodone offers a fast onset of analgesia,
      controlling pain for 12 hours and providing clinically meaningful relief of
      moderate to severe pain and improving quality of life across a broad spectrum of
      pain types. CONCLUSIONS: Oxycodone provides significant pain relief. It has
      relevant points of difference from other opioids and as such may be a suitable
      alternative to morphine.

PMID- 18039432
TI  - Behavioural, emotional, and post-traumatic stress problems in children and
      adolescents, long term after septic shock caused by Neisseria meningitidis.
AB  - OBJECTIVES: To assess the occurrence of a wide range of behavioural, emotional,
      and post-traumatic stress problems in children and adolescents, long term after
      septic shock caused by Neisseria meningitidis (MSS). DESIGN: This study included
      6- to 17-year-old patients who survived MSS and were admitted to the PICU of the
      Medical Centre between 1988 and 2001. To assess behavioural, emotional, and post
      traumatic stress problems, the Child Behaviour Checklist (CBCL), the Teacher's
      Report Form (TRF), and the Youth Self-Report (YSR) were used. METHODS: Parents of
      89 MSS children, aged 6-17 years, completed the CBCL. Teachers of 65 same-aged
      MSS children completed the TRF, and 45 11- to 17-year-old MSS children completed
      the YSR. These data were compared with those from the normative reference groups.
      RESULTS: Overall, the proportions of MSS children scoring in the deviant range
      for problem behaviour were comparable to the proportions in the reference groups,
      according to parents', teachers', and self-reports. As to the level of emotional
      and behavioural problems, mothers of the MSS children reported more somatic
      complaints regarding their children in comparison with the reference groups.
      Severity of illness was not a significant predictor of behavioural, emotional,
      and post-traumatic stress problems. Age at the time of illness was a significant
      predictor of behavioural, emotional, and post-traumatic stress problems in MSS
      children, indicating that the younger the child at the time of illness, the more
      problems were reported by parents at follow-up. CONCLUSION: Overall, the results
      showed long-term behavioural, emotional, and post-traumatic stress outcomes for
      MSS children, which were comparable to those in the general population.

PMID- 18039434
TI  - Utility of health states in chronic kidney disease: a structured review of the
      literature.
AB  - PURPOSE: To document published utilities for health states associated with
      Chronic Kidney Disease (CKD) and End Stage Renal Disease (ESRD) and determine the
      most appropriate values for use in economic models to evaluate renal treatments
      in the UK. METHODS: A structured literature review was conducted (MEDLINE,
      EMBASE, NHS EED and HTA) in order to identify relevant articles published between
      January 1990 and January 2006. In addition searches were conducted on websites of
      Health Technology Assessment (HTA) organizations and the Cost Effectiveness
      Analysis Registry. Articles were reviewed and those not containing utilities
      excluded. Results were assessed on the quality of the elicitation studies and
      their relevance to the UK HTA environment. RESULTS: Thirty-five studies satisfied
      the inclusion criteria. Most studies were conducted in Canada (13), the US (10)
      and the Netherlands (4). Utilities were identified for all/most of the necessary
      states, but scores for individual states differed widely between studies and very
      few studies met the quality criteria. The majority of studies used the time trade
      off (23) and standard gamble (11) to elicit utilities, while only six used EQ-5D.
      Seven studies provided community preferences. Two studies were judged to be
      directly relevant to economic evaluations in the UK. CONCLUSIONS: Many studies
      have estimated utilities in ESRD patients, but only a few have estimated
      utilities based upon public preferences. Further empirical research is needed to
      produce more reliable utilities for economic modelling in the UK, especially in
      chronic kidney disease patients who do not require dialysis.

PMID- 18039435
TI  - [Free resources for evidence-based care].

PMID- 18039436
TI  - [Quality of life in homebound elderly people in a district of Alicante (Spain)].
AB  - OBJECTIVE: To measure health-related quality of life (HRQoL) in homebound elderly
      individuals in the District of San Blas (Alicante, Spain). METHOD: The sample was
      composed of 107 people aged more than 75 years old included in the home care
      program. As a measurement instrument, the Spanish version of COOP/WONCA charts in
      their complete version were used. RESULTS: The mean age was 83.18 years.
      Distribution by sex was 76 (71%) women and 31 (29%) men. The mean overall score
      was 29.7 points with a standard deviation of 5.04. The association between age
      and total score was 0.19, which was statistically significant (p = 0.045).
      Comparison of these two means with Student's t-test for independent samples
      showed no statistically significant differences (t = -580; p > 0.05). When
      differences between men and women in each of the items of the scale were
      analyzed, only "social activities" showed a statistically significant difference
      (t = -2.959; p = 0.04). The time taken to administer the questionnaire was 30 +/-
      5 min. CONCLUSIONS: HRQoL in our population is worse than that in other studied
      populations. Due to the ceiling-floor effect of some of the variables, further
      studies in this type of population are required. The time used in this type of
      population to complete the questionnaire was five times greater than that used in
      other populations.

PMID- 18039437
TI  - [Iodine levels and intake in a population of healthy pregnant women].
AB  - OBJECTIVE: To identify iodine levels in the first two trimesters of pregnancy in
      women attending the primary care center (PCC) of Orihuela (Alicante, Spain), and
      their relationship with food intake and vitamin supplements. METHOD: We performed
      a descriptive prospective study of pregnant women who had a first appointment at
      the PCC midwifery service in November and December 2005. The variables studied
      were urinary iodine levels through isolated sample collections, epidemiological
      variables, and the frequency of intake of iodine-related food and vitamin
      supplements. The variables were collected using a structured questionnaire
      administered through a face-to-face interview with the research team in the first
      and second trimesters of pregnancy. RESULTS: The sample consisted of 104 women.
      Of these, 71.6% had iodine deficiency in the first trimester of pregnancy. This
      percentage was reduced to 30.6% in the second trimester. Statistically
      significant differences were found in intake of mollusks and vitamin supplements
      in relation to urinary iodine excretion. CONCLUSIONS: The mean value of urinary
      iodine excretion in the pregnant women examined revealed a slight deficiency in
      iodine intake in the first trimester, which can represent a risk for fetal
      development.

PMID- 18039439
TI  - [Quality of life 2 years after coronary revascularization].
AB  - OBJECTIVE: To determine the impact of coronary revascularization surgery on
      patients' quality of life and to identify the presence of lifestyles representing
      a risk for coronary heart disease. METHOD: We performed a longitudinal
      prospective study of 150 consecutive patients who underwent coronary surgery over
      a 6-month period. Perceived quality of life was evaluated before the
      intervention, at 6 months (n = 132) and 2 years later (n = 119). As measurement
      instruments, the MOS Health Survey (SF-36), the Nottingham Health Profile (NHP)
      and a questionnaire to identify lifestyles were used. RESULTS: Most of the
      patients (95.8%) were men and were aged more than 50 years old (80.7%). Before
      surgery, significant physical limitations were present in 39.5%, comorbidity in
      79%, prior infarction in 8.7% and three-vessel disease in 68%. The mean length of
      hospital stay was <or= days in 88.2% of the patients. The health benefits were
      greater at 6 months after the intervention than at 2 years, with better perceived
      quality of life in all dimensions of the instruments used to assess quality of
      life (p < 0.001). Comorbidity, the number of risk factors and postoperative
      complications showed no influence on quality of life 6 months after surgery. Two
      years after the intervention, 33.6% of the patients resumed their professional
      activity and most adopted healthier lifestyles. CONCLUSIONS: Coronary
      revascularization substantially improves patients' quality of life, providing
      health benefits 2 years after the intervention.

PMID- 18039438
TI  - [Elevated risk of HIV infection in homosexual men even after contact with the
      health system].
AB  - OBJECTIVE: To determine the incidence of HIV seroconversion and to evaluate the
      characteristics associated with a greater risk of seroconversion in homosexual
      men in the period 2000-2003. METHODS: We performed a dynamic cohort study of all
      homosexual men tested for HIV in 20 ambulatory care centers specialized in
      diagnosing HIV, located in 19 cities in Spain. The characteristics of the men
      were analyzed and the seroconversion incidence rate was calculated among those
      who were followed up. RESULTS: In the period 2000-2003, a total of 10,189 persons
      year of follow-up were accumulated and 167 seroconversions were diagnosed with a
      seroconversion incidence rate of 16.4 per 1,000 persons-year. Most of the
      seroconversions (63%) occurred in men younger than 30 years old. The
      seroconversion rate was higher among homosexual men from Latin America and sub
      Saharan Africa than among Spanish men. CONCLUSIONS: In Spain, the risk of HIV
      transmission among men who have sex with men is still high. Therefore, this
      population continues to be a high priority group in HIV prevention. A proportion
      of HIV diagnoses among immigrants concern infections acquired after their arrival
      to Spain, probably due to conditions of greater social vulnerability. Reinforcing
      and renewing prevention strategies directed at this population would be timely.

PMID- 18039440
TI  - [Role of nurses from Extremadura in the Spanish drug surveillance system (2000
      2005)].
AB  - INTRODUCTION: The main aim of pharmacovigilance, a public health activity, is to
      communicate, collect and evaluate notifications of adverse reactions to drugs
      (ARD) received from health professionals. Among this collective, nurses are in an
      optimal position due to their knowledge of pharmacology and their role in the
      front line of patient care. METHOD: We performed a search of the ARD reported by
      nursing staff in Extremadura from january 1, 2000 to december 31, 2005 through
      the pharmacovigilance information system of Extremadura. RESULTS: A total of
      1,502 ARD were notified to the Spanish pharmacovigilance system by nurses
      throughout Spain (3.32% of the total) and 10 RAM by nurses from Extremadura
      (0.64% of the total number of RAM notified by nurses). The highest number of ARD
      corresponded to the year 2000, with 20% of the total being urticaria. The
      causative agents were vaccines against diphtheria, tetanus, pertussis and
      poliomyelitis (30% of the total). According to the notifiers, 50% corresponded to
      the extrahospital setting. Only one ARD required emergency care, while 40% of
      affected individuals required drug therapy to alleviate the effects of the ARD.
      Seventy percent of the ARD were mild, while the remainder were moderate. ARD
      occurred in men and women equally, and the mean age of affected individuals was
      37.4 years. CONCLUSION: ARD are underreported by nurses, influenced by low
      motivation to notify these events and lack of knowledge of how they should be
      reported.

PMID- 18039441
TI  - [Treatment of a long-standing lesion with early stimulation of wound healing].
AB  - We report the case of a 62-year-old man with a long-standing lesion on the dorsum
      of his right foot. The patient had diabetes mellitus and was under treatment with
      oral antidiabetic agents. The lesion contained abundant necrotic tissue, the
      borders showed evident signs of inflammation, and there was abundant prurulent
      exudate. Symptoms of infection were observed and a long course of broad-spectum
      antibiotics was administered. Given the site and characteristics of the lesion,
      unselective cleansing techniques were avoided. Collagen powder and silver
      dressing were applied to control bacteria and finally alginate and silicone
      sponge dressings were applied to soak up the exudate and keep the area moist.
      After 22 weeks of treatment, evident signs of improvement were observed, allowing
      the patient to perform activities of daily living.

PMID- 18039442
TI  - [Continuous extracorporeal stool transport (CEST) in a preterm infant with
      proximal ileostomy: report of a case].
AB  - Children with ileostomy can develop short bowel syndrome (SBS), characterized by
      malabsorption of nutrients and consequent malnutrition. Continuous extracorporeal
      stool transport (CEST) consists of collecting and transporting the intestinal
      effluent drained from the proximal stoma to the portion of the distal intestine.
      Thus, intestinal flux can be maintained, while digestion and absorption
      approximate real physiology until defecation. We describe the case of a preterm
      newborn who suffered from necrotizing enterocolitis and who underwent resection
      of the small intestine and implantation of four stomas. CEST was applied,
      allowing early reduction of total enteral nutrition and its subsequent
      withdrawal. This in turn allowed the reduction of those complications associated
      to the continous use of this therapy (risk of infection and hepatobiliary
      alterations) and permited keeping the distal intestine in optimal conditions
      until reconstructive surgery could be performed. Our experience demonstrates that
      CEST is a safe and relatively simple technique with good results that allows
      restoration of intestinal homeostasis in neonates with SBS.

PMID- 18039443
TI  - [Obesity prevention program for children in rural areas].

PMID- 18039444
TI  - [Predictors of treatment adherence in children with type 1 diabetes mellitus].

PMID- 18039445
TI  - [Spanish nursing journals have become less isolated].

PMID- 18039447
TI  - [Professional competence for the care of critical patients: beyond specialities].
AB  - OBJECTIVE: To elaborate a working document to describe the professional
      competence (knowledge, skills, and attitudes) required of a physician for the
      care of critical patients, regardless of the physician's specialty and centered
      on the patients' needs. METHODS: This study was carried out through field work
      using qualitative methodology over the 12-month period comprising 2004. The
      document was elaborated in four stages: 1) conceptual delimitation; 2) selection
      of working definitions and classifications; 3) identification of knowledge,
      skills, and attitudes necessary for the management of critical patients; and 4)
      final draft of the competence document. RESULTS: A total of 146 areas of
      competence were identified; of these, 33% were related to knowledge, 52% to
      skills, and the remaining 15% to attitudes. CONCLUSIONS: This study can help to
      ensure that critical patients will be cared for by physicians capable of
      identifying their problems and managing them appropriately, regardless of the
      physicians' specialty background. In responding to this situation, the document
      recognizes the participation of physicians trained in diverse specialties in the
      care of the critical patient by scaling the knowledge required at different
      levels of care.

PMID- 18039448
TI  - [Implementation and evaluation of a protocol for continuous insulin perfusion in
      critical patients].
AB  - OBJECTIVE: To analyze the efficacy and safety of a protocol for the continuous
      infusion of insulin to maintain blood glucose levels between 100 and 140 mg/dl,
      evaluating the results by a method that takes all of the hours of treatment into
      consideration. DESIGN: Prospective observational study over a two-month period
      and follow up until the end of insulin perfusion. CONTEXT: Twenty three-bed
      polyvalent ICU. PATIENTS: Fifty consecutive patients >18 years of age with 2
      episodes of glycemia >140 mg/dl separated by 4-6 hours. Patients on an oral diet
      were excluded. INTERVENTION: The perfusion rate and the frequency of glycemia
      monitoring were set according to the nursing staff's protocol. MAIN VARIABLES OF
      INTEREST: Days of insulin perfusion and number and value of the blood glucose
      measurements taken. Episodes of hypoglycemia, mean blood glucose level, the
      percentage of hyperglycemia episodes, and the number of hours that the patient's
      blood glucose was in each range. RESULTS: The mean duration of treatment was 15.6
      days (SD 12). A total of 17,768 hours and 8,111 blood glucose measurements were
      collected. 55.5% of the blood glucose measurements were between 100-140 mg/dl,
      and this represents 63.9% of the hours. The mean blood glucose level was 133
      mg/dl. Only 2 episodes of severe hypoglycemia (<45 mg/dl) occurred. CONCLUSION:
      The protocol was safe and enabled adequate control of blood glucose levels. The
      analysis of all of the hours of treatment might provide more data than a simple
      study of the percentages of blood glucose measurements within the normal range
      and the mean blood glucose level.

PMID- 18039449
TI  - [High PEEP vs. conventional PEEP in the acute respiratory distress syndrome: a
      systematic review and meta-analysis].
AB  - OBJECTIVE: To perform a systematic review and meta-analysis of the literature to
      evaluate the effects of high PEEP versus conventional PEEP on mortality and on
      the risk of barotrauma in patients with the acute respiratory distress syndrome
      (ARDS). SOURCE OF DATA: Computer search of Medline, Embase, CINAHL, CANCERLIT,
      Pascal-Biomed, ACP Journal Club, Cochrane library (CDSR, DARE, CCTR), ISI
      Proceedings, Current Contents, and Web of Science, as well as manual search of
      selected references. SELECTION OF STUDIES: Controlled random clinical trials
      published after NAECC (1994) that evaluated the effect of two levels of PEEP and
      that reported the mortality and incidence of barotrauma in the series. DATA
      EXTRACTION: By two investigators working independently, with discrepancies
      resolved by group consensus. Contingency tables were elaborated and the RRs with
      corresponding confidence intervals were obtained for each study. RESULTS: Four
      articles were selected for the meta-analysis of mortality and three for the meta
      analysis of barotrauma. No effects of PEEP level on mortality were found (RR
      0.73, 95% CI: 0.49 to 1.10) or on the incidence of barotrauma (RR 0.50, 95% CI:
      0.14 to 1.73). However, an analysis of the studies in which PEEP was
      individualized in function of Pflex showed a significant decrease in mortality
      (RR 0.59, 95% CI: 0.43 to 0.82) (p=0.001) CONCLUSIONS: The use of high or
      conventional PEEP in function of oxygenation does not affect mortality or the
      incidence of barotrauma in patients with ARDS. However, there might be a decrease
      in mortality associated to high PEEP individualized in function of the pulmonary
      mechanics of each patient.

PMID- 18039450
TI  - [Acute coronary syndrome (ACS) with elevated ST segment: consensus strategy for
      early reperfusion. The Public Enterprise for Health Emergencies and the ARIAM
      Project Andalusia].
AB  - The two pillars of the appropriate management of patients with ST-elevation
      myocardial infarction (STEMI) are immediate access to defibrillation and early
      reperfusion. The Public Enterprise for Health Emergencies (EPES) and the
      Andalusian ARIAM (Analysis of the Delay in the Treatment of Acute Myocardial
      Infarction) Project aim to implement a common basic strategy that can be adapted
      to local situations in order to facilitate decision making about the treatment of
      these patients. CONTEXT: The Autonomous Community of Andalusia. PERIOD: March-May
      2006. PARTICIPANTS: Professionals that attend patients with STEMI: physicians in
      the EPES' work group on cardiological processes, emergency department physicians,
      and physicians working in the intensive care units in the hospitals of the public
      healthcare system of Andalusia. APPROACH: Levels of evidence. The levels of
      evidence laid out in the 2004 ACC/AHA Clinical Practice Guidelines. REACHING A
      CONSENSUS: A meeting was held to discuss the aspects to be included in the
      document. A working document was drafted and distributed to the participants via
      email. The final consensus document was drafted at another meeting. CONCLUSIONS:
      The consensus document establishes the following priorities: 1. To apply the set
      of general measures recommended for the care of STEMI patients strictly and
      appropriately 2. To foster the use of early reperfusion in as many patients as
      possible, promoting the extension of fibrinolysis outside of hospitals and
      referral to a center with facilities for primary percutaneous coronary
      intervention. 3. To monitor and evaluate the management of these patients, with
      special attention placed on outcome and safety.

PMID- 18039451
TI  - [Applications of transcranial color-coded duplex sonography in monitoring
      neurocritical patients].
AB  - Transcranial sonography is a common tool for monitoring neurocritical patients.
      Transcranial color-coded duplex ultrasonography enables hemodynamic and
      structural study of the cerebral parenchyma in these patients. Its advantages
      over conventional ultrasonography are evident and are derived from direct
      visualization of the vessel to be studied and appropriate adjustment of the
      sample volume and angle of insonation. The use of ultrasonographic contrast
      agents enables conclusive findings in practically 100% of cases and allows
      cerebral perfusion to be studied at the bedside using semiquantitative methods.
      This review aims to show the applications of transcranial color-coded duplex
      ultrasonography for monitoring neurocritical patients in intensive care units.

PMID- 18039452
TI  - [Early interruption of clinical trials: too good to be true?].
AB  - The interruption of a randomized clinical trial when the experimental treatment
      is clearly superior is an ethical obligation. However, performing multiple
      intermin statistical analyses and the early interruption of the trial increase
      the possibility of alpha error, favor the overestimation of the effect, and
      facilitate the introduction of ineffective therapies data monitoring. Currently
      available empirical evidence suggests that early interrupted clinical trials
      overestimate the effects of new treatments and that the reasons used to justify
      interrupting the trial are often not sufficiently specified. This underlines the
      need for truly independent data monitoring committees and recommends the use of
      predefined restrictive rules for the interruption of a trial. Furthermore,
      clinicians should provide themselves with an adequate dose of skepticism and
      critical reading skills to enable them to explore some key aspects of these
      studies.

PMID- 18039453
TI  - [Overdose of metformin secondary to acute renal insufficiency: a report of six
      cases].
AB  - Metformin is a biguanide used in the treatment of obese adults with type 2
      diabetes mellitus; metformin decreases mortality by 36% in comparison to
      conventional treatment. Metformin administration has certain contraindications
      that, when ignored, especially in the case of acute renal insufficiency, leads to
      the accumulation of the drug and consequent lactic acidosis that can be fatal. We
      present 6 patients with acute renal insufficiency that experienced extreme acute
      metabolic acidosis (pH <6.90 and bicarbonate <5 mEq/l) and increased anion gap
      while receiving metformin for the treatment of diabetes. Serum lactic acid, only
      evaluated in the 4 patients that survived, was high. Two patients died after
      cardiac arrest that could have been avoided. In conclusion, lactic acidosis
      appearing during metformin treatment for diabetes requires rapid diagnosis and
      treatment to enable the drug to be withdrawn and prolonged continuous
      hemofiltration or hemodialysis with bicarbonate to be initiated.

PMID- 18039454
TI  - [Unusual position of a pacemaker cable].

PMID- 18039455
TI  - [Presence of Osborn's J wave in hypothermia].

PMID- 18039456
TI  - [Use of methylene blue in the treatment of vasoplegic syndrome after heart
      surgery: other perspectives on the case].

PMID- 18039458
TI  - [Intensive medicine images. A 75-year-old woman with a history of pulmonary
      embolism].

PMID- 18039461
TI  - Energy transfer processes in Gloeobacter violaceus PCC 7421 that possesses
      phycobilisomes with a unique morphology.
AB  - We examined energy transfer dynamics in phycobilisomes (PBSs) of cyanobacteria in
      relation to the morphology and pigment compositions of PBSs. We used Gloeobacter
      violaceus PCC 7421 and measured time-resolved fluorescence spectra in three types
      of samples, i.e., intact cells, PBSs, and rod assemblies separated from cores.
      Fremyella diplosiphon, a cyanobacterial species well known for its complementary
      chromatic adaptation, was used for comparison after growing under red or green
      light. Spectral data were analyzed by the fluorescence decay-associated spectra
      with components common in lifetimes with a time resolution of 3 ps/channel and a
      spectral resolution of 2 nm/channel. This ensured a higher resolution of the
      energy transfer kinetics than those obtained by global analysis with fewer
      sampling intervals. We resolved four spectral components in phycoerythrin (PE),
      three in phycocyanin (PC), two in allophycocyanin, and two in photosystem II. The
      bundle-like PBSs of G. violaceus showed multiple energy transfer pathways; fast (
      approximately 10 ps) and slow ( approximately 100 ps and approximately 500 ps)
      pathways were found in rods consisting of PE and PC. Energy transfer time from PE
      to PC was two times slower in G. violaceus than in F. diplosiphon grown under
      green light.

PMID- 18039462
TI  - Dopamine differentially induces aggregation of A53T mutant and wild type alpha
      synuclein: insights into the protein chemistry of Parkinson's disease.
AB  - Aggregation of alpha-synuclein is known to be a causal factor in the genesis of
      Parkinson's disease and Dementia with Lewy bodies. Duplication and/or
      triplication and mutation of the alpha-synuclein gene are associated with
      sporadic and familial Parkinson's disease. Synucleinopathies appear to primarily
      affect dopaminergic neurons. The present studies investigate the role of dopamine
      in alpha-synuclein aggregation through NMR. Dopamine causes aggregation of both
      wild type and A53T mutant alpha-synuclein in a temperature-dependent manner, but
      the mutant A53T shows a greater propensity to aggregate in the presence of
      dopamine only at 37 degrees C. A single point mutation in the alpha-synuclein
      A53T mutant gene results in a structural change in the protein and drastically
      increases its propensity to aggregate in the presence of dopamine. The present
      data indicate that mutation in the alpha-synuclein gene may predispose the
      protein to dopamine-induced aggregation, thereby contributing to disease
      pathogenesis.

PMID- 18039463
TI  - Crystal structure of histone demethylase LSD1 and tranylcypromine at 2.25 A.
AB  - Transcriptional activity and chromatin structure accessibility are correlated
      with the methylation of specific histone residues. Lysine-specific demethylase 1
      (LSD1) is the first discovered histone demethylase, which demethylates Lys4 or
      Lys9 of histone H3, using FAD. Among the known monoamine oxidase inhibitors,
      tranylcypromine (Parnate) showed the most potent inhibitory effect on LSD1.
      Recently, the crystal structure of LSD1 and tranylcypromine was solved at 2.75 A,
      revealing a five-membered ring fused to the flavin of LSD1. In this study, we
      refined the crystal structure of the LSD1-tranylcypromine complex to 2.25 A. The
      five-membered ring model did not fit completely with the electron density, giving
      R(work)/R(free) values of 0.226/0.254. On the other hand, the N(5) adduct gave
      the lowest R(work)/R(free) values of 0.218/0.248, among the tested models. These
      results imply that the LSD1-tranylcypromine complex is not completely composed of
      the five-membered adduct, but partially contains an intermediate, such as the
      N(5) adduct.

PMID- 18039464
TI  - Grafting of material-binding function into antibodies Functionalization by
      peptide grafting.
AB  - Quite recently, a few antibodies against bulk material surface have been selected
      from a human repertoire antibody library, and they are attracting immense
      interest in the bottom-up integration of nanomaterials. Here, we constructed
      antibody fragments with binding affinity and specificity for nonbiological
      inorganic material surfaces by grafting material-binding peptides into loops of
      the complementarity determining region (CDR) of antibodies. Loops were replaced
      by peptides with affinity for zinc oxide and silver material surfaces. Selection
      of CDR loop for replacement was critical to the functionalization of the grafted
      fragments; the grafting of material-binding peptide into the CDR2 loop
      functionalized the antibody fragments with the same affinity and selectivity as
      the peptides used. Structural insight on the scaffold fragment used implies that
      material-binding peptide should be grafted onto the most exposed CDR loop on
      scaffold fragment. We show that the CDR-grafting technique leads to a build-up
      creation of the antibody with affinity for nonbiological materials.

PMID- 18039465
TI  - Cryo-electron microscopy of coagulation Factor VIII bound to lipid nanotubes.
AB  - Factor VIII (FVIII) is a key protein in blood coagulation, deficiency or
      malfunction of which causes Haemophilia A. The sole cure for this condition is
      intravenous administration of FVIII, whose membrane-bound structure we have
      studied by Cryo-electron microscopy and image analysis. Self-assembled lipid
      nanotubes were optimised to bind FVIII at close to native conditions. The tubes
      diameter was constant at 30 nm and the lipid bilayer resolved. The FVIII
      molecules were well defined, forming an 8.5 nm thick outer layer, and appeared to
      reach the hydrophobic core of the bilayer. The two known FVIII atomic models were
      superimposed with the averaged 2D protein densities. The insertion of the FVIII
      within the membrane was evaluated, reaffirming that the membrane-binding C2 or C1
      C2 domain(s) fully penetrate the outer leaflet of the lipid layer. The presented
      results lay the basis for new models of the FVIII overall orientation and
      membrane-binding mechanism.

PMID- 18039466
TI  - Nanog inhibits the switch of myogenic cells towards the osteogenic lineage.
AB  - The homeodomain transcription factor Nanog has been implicated in inhibiting
      differentiation and controlling pluripotency of embryonic stem (ES) cells. We
      used ectopic expression of Nanog in the myogenic committed C2 cells to dissect
      these properties. Expression of Nanog in C2 cells does not alter terminal muscle
      differentiation but has a profound effect on their switch to differentiate along
      the osteogenic lineage upon BMP treatment. Gene expression profiling revealed
      that ERK 1/2 phosphorylation, alkaline-phosphatase activity and osteocalcin
      expression were induced to much lower extent and remained suppressed even after
      96h. in Nanog expressing C2 cells, compared to control C2 cells. Hence, Nanog
      does not inhibit terminal differentiation of committed cells but it is an
      inhibitor of trans-differentiation that is dependent on de-novo activation of
      gene transcription.

PMID- 18039468
TI  - Small stress molecules inhibit aggregation and neurotoxicity of prion peptide 106
      126.
AB  - In prion diseases, the posttranslational modification of host-encoded prion
      protein PrP(c) yields a high beta-sheet content modified protein PrP(sc), which
      further polymerizes into amyloid fibrils. PrP106-126 initiates the conformational
      changes leading to the conversion of PrP(c) to PrP(sc). Molecules that can
      defunctionalize such peptides can serve as a potential tool in combating prion
      diseases. In microorganisms during stressed conditions, small stress molecules
      (SSMs) are formed to prevent protein denaturation and maintain protein stability
      and function. The effect of such SSMs on PrP106-126 amyloid formation is explored
      in the present study using turbidity, atomic force microscopy (AFM), and cellular
      toxicity assay. Turbidity and AFM studies clearly depict that the SSMs-ectoine
      and mannosylglyceramide (MGA) inhibit the PrP106-126 aggregation. Our study also
      connotes that ectoine and MGA offer strong resistance to prion peptide-induced
      toxicity in human neuroblastoma cells, concluding that such molecules can be
      potential inhibitors of prion aggregation and toxicity.

PMID- 18039467
TI  - Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase
      reactant.
AB  - Fibrinogen-like protein 1 (FGL1) is a hepatocyte derived protein that is
      upregulated in regenerating rodent livers following partial hepatectomy. It has
      been implicated as a mitogen for liver cell proliferation. In this study, we show
      that recombinant human IL-6 induces FGL1 expression in Hep G2 cells in a pattern
      similar to those of acute phase reactants. Following induction of acute
      inflammation in rats by subcutaneous injection of turpentine oil, serum FGL1
      levels are also enhanced. Although, a recent report suggests that FGL1 associates
      almost exclusively with the fibrin matrix, we report here that approximately 20%
      of the total plasma FGL1 remains free. The enhancement of FGL1 levels in vitro by
      IL-6 and its induction after turpentine oil injection suggest that it is an acute
      phase reactant. Its presence in bound and free forms in the blood also implies
      biological roles that extend beyond the proposed autocrine effect it has on
      hepatocytes during regeneration.

PMID- 18039469
TI  - Promising anti-Alzheimer's dimer bis(7)-tacrine reduces beta-amyloid generation
      by directly inhibiting BACE-1 activity.
AB  - The regulation of alpha-, beta-, (BACE-1), and gamma-secretase activities to
      alter beta-amyloid (Abeta) generation is considered to be one of the most
      promising disease-modifying therapeutics for Alzheimer's disease. In this study,
      the effect and mechanisms of bis(7)-tacrine (a promising anti-Alzheimer's dimer)
      on Abeta generation were investigated. Bis(7)-tacrine (0.1-3muM) substantially
      reduced the amounts of both secreted and intracellular Abeta in Neuro2a APPswe
      cells without altering the expression of APP. sAPPalpha and CTFalpha increased,
      while sAPPbeta and CTFbeta decreased significantly in Neuro2a APPswe cells
      following the treatment with bis(7)-tacrine, indicating that bis(7)-tacrine might
      activate alpha-secretase and/or inhibit BACE-1 activity. Furthermore, bis(7)
      tacrine concentration-dependently inhibited BACE-1 activity in cultured cells,
      and also in recombinant human BACE-1 in a non-competitive manner with an IC(50)
      of 7.5muM, but did not directly affect activities of BACE-2, Cathepsin D, alpha-
      or gamma-secretase. Taken together, our results not only suggest that bis(7)
      tacrine may reduce the biosynthesis of Abeta mainly by directly inhibiting BACE-1
      activity, but also provide new insights into the rational design of novel anti
      Alzheimer's dimers that might have disease-modifying properties.

PMID- 18039470
TI  - FoxA1 as a lineage-specific oncogene in luminal type breast cancer.
AB  - The forkhead transcription factor FoxA1 is thought to be involved in mammary
      tumorigenesis. However, the precise role of FoxA1 in breast cancer development is
      controversial. We examined expression of FoxA1 in 35 human breast cancer cell
      lines and compared it with that of ErbB2, a marker of poor prognosis in breast
      cancer. We found that FoxA1 is expressed at high levels in all ErbB2-positive
      cell lines and a subset of ErbB2-negative cell lines. Down-regulation of FoxA1 by
      RNA interference significantly suppressed proliferation of ErbB2-negative and
      FoxA1-positive breast cancer cell lines. Down-regulation of FoxA1 also enhanced
      the toxic effect of Herceptin on ErbB2-positive cell lines through induction of
      apoptosis. Taken together with previous data that FoxA1 is a marker of luminal
      cells in mammary gland, our present results suggest that FoxA1 plays an important
      role as a lineage-specific oncogene in proliferation of cancer cells derived from
      mammary luminal cells.

PMID- 18039471
TI  - An efficient, one-pot synthesis of various ceramide 1-phosphates from sphingosine
      1-phosphate.
AB  - An efficient, one-pot procedure for the synthesis of ceramide 1-phosphates with
      varying N-acyl substituents, to serve as tool compounds for analytical and
      biological investigations, was developed. Sphingosine 1-phosphate was silylated
      in situ to increase its solubility and to protect the 3-hydroxy functionality and
      then allowed to react with activated acid derivatives in the presence of
      diisopropylethylamine. Simultaneous cleavage of the silyl protecting groups and
      separation from reagents and by-products was achieved by medium pressure
      chromatography on reversed phase material. Thus, ceramide 1-phosphates with
      various fatty acid chains and with fluorescent and affinity labels attached to
      the sphingoid backbone were prepared in good yields.

PMID- 18039472
TI  - Association of elevated plasma B-type natriuretic peptide levels with paroxysmal
      atrial fibrillation in patients with nonobstructive hypertrophic cardiomyopathy.
AB  - OBJECTIVES: To investigate the relationship between the plasma B-type natriuretic
      peptide (BNP) level and the occurrence of atrial fibrillation (AF) in
      nonobstructive hypertrophic cardiomyopathy (HCM) patients. METHODS: Patients
      (n=97) were classified into chronic AF (CAF; n=14), paroxysmal AF (PAF; n=18) and
      normal sinus rhythm (NSR; n=65) groups. The plasma BNP values were analyzed with
      logarithmic transformation. RESULTS: The PAF group showed significantly higher
      plasma BNP levels than the NSR group [mean (range; -l SD and +1 SD); 248.3
      (143.5, 429.5) vs. 78.2 (27.9, 218.8 ng/L), p<0.0001]. The CAF group also showed
      significantly higher plasma BNP levels than the NSR group [291.1 (161.4, 524.8
      ng/L), p<0.0001]. Multivariate analysis with other clinical factors selected
      association of PAF as one of the factors that increased the plasma BNP level.
      CONCLUSIONS: The present study indicated that plasma BNP level is clinically
      useful for identification of nonobstructive HCM patients who have a risk of PAF.

PMID- 18039473
TI  - Redox characteristics of the eukaryotic cytosol.
AB  - The eukaryotic cytoplasm has long been regarded as a cellular compartment in
      which the reduced state of protein cysteines is largely favored. Under normal
      conditions, the cytosolic low-molecular weight redox buffer, comprising primarily
      of glutathione, is highly reducing and reactive oxygen species (ROS) and
      glutathionylated proteins are maintained at very low levels. In the present
      review, recent progress in the understanding of the cytosolic thiol-disulfide
      redox metabolism and novel analytical approaches to studying cytosolic redox
      properties are discussed. We will focus on the yeast model organism,
      Saccharomyces cerevisiae, where the combination of genetic and biochemical
      approaches has brought us furthest in understanding the mechanisms underlying
      cellular redox regulation. It has been shown in yeast that, in addition to the
      enzyme glutathione reductase, other mechanisms may exist for restricting the
      cytosolic glutathione redox potential to a relatively narrow interval. Several
      mutations in genes involved in cellular redox regulation cause ROS accumulation
      but only moderate decreases in the cytosolic glutathione reducing power. The
      redox regulation in the cytosol depends not only on multiple cytosolic factors
      but also on the redox homeostasis of other compartments like the secretory
      pathway and the mitochondria. Possibly, the cytosol is not just a reducing
      compartment surrounding organelles with high oxidative activity but also a milieu
      for regulation of the redox status of more than one compartment. Although much
      has been learned about redox homeostasis and oxidative stress response several
      important aspects of the redox regulation in the yeast cytosol are still
      unexplained.

PMID- 18039474
TI  - Novel long-lasting interferon alpha derivatives designed by glycoengineering.
AB  - Human alpha interferons (hIFN-alpha) comprise a family of closely related
      proteins that block viral infection, inhibit cell proliferation and modulate cell
      differentiation. Recombinant hIFN-alpha2 has proved useful for the treatment of a
      variety of human viral diseases and cancers. However, the clinical use of this
      cytokine has been restricted due to its short circulating half-life, which makes
      frequent dosing over an extended period necessary. To circumvent this problem, a
      glycoengineering strategy was carried out using site-directed mutagenesis.
      Fourteen mutants were constructed by the insertion of one N-glycosylation
      consensus sequence into different positions of the cytokine. Mutations were
      focused on amino acid positions that were believed not to be critical for the
      protein's structure or function. Taking into account the retained specific in
      vitro bioactivity and the higher carbohydrate content, five N-glycosylation
      positions were selected to be introduced into the molecule. Successive increases
      in molecular weight were observed after each addition of a functional consensus
      sequence, resulting in analogs with 4 and 5 N-linked carbohydrates (4N- and 5N
      IFN) with increased size and charge, factors that reduce renal clearance of
      proteins. Pharmacokinetic experiments showed a similar behavior of 4N- and 5N-IFN
      variants, with a 25-fold increase in the elimination half-life and a 20-fold
      decrease in the systemic clearance rate compared with the non-glycosylated rhIFN
      alpha2 following subcutaneous administration to rats. Besides, both distribution
      and elimination half-lives of the 4N analog were longer in comparison with the
      non-glycosylated cytokine, determining a 10-fold increase in the area under the
      curve after intravenous inoculation. Thus, herein we describe for the first time
      heavily glycosylated IFN analogs with a remarkable improvement in pharmacokinetic
      properties, which allow us to project drugs that combine less frequency of
      administration with enhanced therapeutic efficacy.

PMID- 18039485
TI  - Report on the 3rd International FESTEM Symposium on "Recent advances in trace
      element research: from experiments to nutritional and clinical applications in
      humans", Santiago de Compostela, Spain, May 16-19, 2007.

PMID- 18039475
TI  - AH23848 accelerates inducible nitric oxide synthase degradation through
      attenuation of cAMP signaling in glomerular mesangial cells.
AB  - Excessive release of nitric oxide (NO) by mesangial cells contributes to the
      pathogenesis of glomerulonephritis. Prostaglandin E(2) (PGE(2)) produced at
      inflammatory sites regulates the release of NO through its downstream signaling.
      In glomerular mesangial cells (MES-13 cells), PGE(2) modulated NO production
      mainly through EP4 receptor in a cAMP-dependent manner. Lipopolysaccharide and
      interferon-gamma (LPS+IFNgamma)-induced NO production, inducible nitric oxide
      synthase (iNOS) gene and protein expression were greatly inhibited by AH23848, an
      EP4 antagonist. Further investigation indicated that AH23848 attenuated
      endogenous cAMP accumulation in MES-13 cells and modulated NO production through
      declination of iNOS gene expression and acceleration of iNOS protein degradation.
      AH23848 downregulated the iNOS protein in MES-13 cells through protein kinase A
      (PKA) since KT5720, a PKA-specific inhibitor, reduced iNOS protein stability. A
      short exposure of activated MES-13 cells to okadaic acid augmented iNOS activity.
      AH23848 and KT5720 attenuated serine/threonine phosphorylation of iNOS protein in
      LPS + IFNgamma-stimulated MES-13 cells. The results of this study led us to
      speculate that cAMP might regulate iNOS-stimulated NO synthesis through
      posttranslational mechanisms. Attenuation of cAMP signaling and the
      phosphorylation status of the iNOS protein may account for the effect of AH23848
      in accelerating iNOS protein degradation in MES-13 cells.

PMID- 18039486
TI  - Manganese species from human serum, cerebrospinal fluid analyzed by size
      exclusion chromatography-, capillary electrophoresis coupled to inductively
      coupled plasma mass spectrometry.
AB  - Manganese (Mn) at high concentrations can have adverse effects on health, mainly
      because of its toxicity to the central nervous system. Health impacts of Mn are
      known mostly from occupational health studies, but the exact mechanisms how Mn,
      being bound to transferrin (TF) in the blood, enters the brain--are unknown. Mn
      speciation at the neural barriers can help to obtain more information about the
      pathways and carriers. This paper summarizes investigations on the size
      distribution of Mn carriers (e.g. proteins, peptides, carbonic acids) in serum
      before the neural barriers and in cerebrospinal fluid (CSF) behind them as a
      first characterization step of the Mn carriers being involved in moving Mn across
      the neural barriers. Further identification of Mn-species in CSF was successfully
      achieved by CZE-inductively coupled plasma (ICP)-dynamic reaction cell (DRC)-mass
      spectrometry (MS). Serum samples showed Mn mean concentrations of 1.7+/-0.8
      microg L(-1). The size distribution of Mn-carriers showed a main peak in the
      TF/albumin size fitting to the known physiological ligands. However, also an
      increasing Mn peak at 700 Da with increasing total Mn concentration was seen.
      Samples of CSF showed Mn mean concentrations of 2.6 microg L(-1)=48 nM. In CSF Mn
      was found to be mostly bound to low-molecular-mass (LMM)-Mn carriers in the range
      of 640-680 Da. This is similar to the LMM compound in serum and to Mn-citrate
      complexes suggested to be present in body fluids. Citrate concentration was 573
      microM, thus being in huge excess compared to Mn. CSF was further analyzed by CZE
      ICP-DRC-MS. Several Mn-species were monitored and mostly identified. The most
      abundant Mn-species was Mn-citrate at a concentration of around 0.7 microg Mn L(
      1).

PMID- 18039487
TI  - Determination of iodine in human milk and infant formulas.
AB  - The aim of this study was to develop a method to determine iodine in human milk
      and infant formulas using ICP-MS. The milk samples were digested using an
      alkaline digestion (5% NH(3), 45 W, 2 min and 30s), and the method was validated
      using a certified reference material (CRM) BCR CRM151. On the other hand the milk
      was separated in three fractions, whey, fat and caseins using ultracentrifugation
      (15 min, 4 degrees C, 50,000 rpm) and the iodine was determined in the different
      fractions. About 27 samples of different infant formulas and 14 samples of human
      milk have been studied. In the human milk the values found were between 144+/
      93.2 microg kg(-1), whereas in the infant formulas the values were 53.3+/-19.5.
      For both types of samples the bigger amount of iodine is in the whey fraction,
      between 80% and 90%, whereas in the fat there is about a 2% of the total iodine
      and in the casein fraction the levels are between 5% and 10% depending on the
      type of sample.

PMID- 18039488
TI  - Optimization of the trace element determination by ICP-MS in human blood serum.
AB  - The ICP-MS for simultaneous trace element determination in human blood has
      prevailed as the most suitable methodology for clinical aims because of its
      rapidity, detection limits and minimal sample quantity needed for analysis. As
      the proteic matrix is high, it is necessary to fine-tune the ICP-MS Agilent 7500i
      with autosampler CETAC ASX-500 and ISIS System connected, and further we have to
      the sample pre-treatment in order to obtain good results. The study of the
      results shows that the best pre-treatment for blood serum samples consists of a
      basic treatment by 1/10 dilution with a solution of EDTA and NH(4)OH, with a
      detection limit of the order of mug/L and a reduction of the necessary patient
      sample volume to 2 mL.

PMID- 18039489
TI  - New ways in qualitative and quantitative protein analysis: nano chromatography
      coupled to element mass spectrometry.
AB  - The potential of inductively coupled plasma-mass spectrometry (ICP-MS), which
      allows element-specific detection of heteroelements (e.g. Se and S) incorporated
      in protein structures, is highlighted for sensitive qualitative and quantitative
      protein analysis. ICP-MS coupled to separation techniques such as size exclusion
      chromatography and gel electrophoresis (via laser ablation) can be employed at
      different steps in the proteomic workflow. Special emphasis is made on the
      couplings of capillary and nanoHPLC to ICP-MS that required the development of
      dedicated interfaces. Element-specific peptide mapping by nanoHPLC-ICP-MS has
      turned out to be a key technique in combination with peptide sequencing via
      nanoHPLC-electrospray MS. This could impressively be demonstrated for the
      identification of selenium-containing proteins in selenium-rich yeast.
      Furthermore the potential of sulfur isotope dilution analysis in nanoHPLC-ICP-MS
      is presented as generic tool for highly accurate, absolute protein
      quantification.

PMID- 18039490
TI  - Separation and determination of Se-compounds by liquid chromatography coupled
      with electrospray mass spectrometry.
AB  - A method for Selenocystine and Selenomethionine determination by LC-ES-MS was
      developed in this work. The mass spectrometer was used in a positive mode and the
      m/z used for the identification of Selenomethionine and Selenocystine were 198.35
      and 337.15, respectively. The selenium species were separated using a LC system.
      A silica chromatographic column (ZORBAX Eclipse XDB-C(8) of 50 mm length and 2.1
      mm internal diameter (particle size 3.5 microm)) was used. The separation was
      realised in isocratic mode, using methanol:water (1:1) with 1% of acetic acid and
      a flow rate of 200 microL min(-1). The developed method was precise (RSD of 4.5%
      and 3.9% for Selenomethionine and Selenocystine, respectively) and sensible
      (limit of detection (LOD) 0.06 and 0.99 mg L(-1) for selenomethionine and
      selenocystine, respectively).

PMID- 18039491
TI  - Validation of determination of lead (Pb) in blood by electrothermal atomic
      absorption spectrometry (ETAAS) on the basis of interlaboratory comparison data.
AB  - ISO 15189 standard establishes a requirement to periodically revalidate
      analytical methods for the determination of trace elements like Pb in blood, as
      conditions change and technical advances are made. The aim of this study was to
      revalidate an electrothermal atomic absorption spectrometry (ETAAS) method for
      determination of Pb in blood over the microrange 25-35 microg/dL, on the basis of
      historical results of interlaboratory comparison programmes. Precision and
      inaccuracy were estimated by analysis of records of an external quality control
      programme for Pb (PICC-PbS). The precision and inaccuracy values obtained were
      both less than 5%, highly satisfactory in view of the validation requirement that
      precision and inaccuracy be less than 10%. These findings demonstrate the
      effectiveness of this new validation methodology, which does not require any
      disruption of the laboratory's routine activity, and which can be used even if
      the method in question has not been validated previously at that laboratory.

PMID- 18039492
TI  - Electrothermal atomic absorption spectrometry determination of aluminium in
      parenteral nutrition and its components.
AB  - Aluminium concentration in samples of total parenteral nutrition solutions and
      samples of their individual components were analysed to know the exposure to this
      element. The median aluminium content obtained for the total parenteral nutrition
      solutions was 105.7 microg/L; for their individual components, 10% calcium
      gluconate and 1M monopotasic phosphate were the most contaminated, as well as the
      1M sodium bicarbonate. The great variability found in the aluminium content of
      solutions suggests that contamination occurs during the manufacturing process.

PMID- 18039493
TI  - Analysis of brain regional distribution of aluminium in rats via oral and
      intraperitoneal administration.
AB  - In the present work, accumulation and distribution of aluminium in the rat brain
      following both intraperitoneal and oral administration were studied.
      Electrothermal atomic absorption spectrometry was used to determine aluminium
      concentration in different brain areas (cerebellum, ventral midbrain, cortex,
      hippocampus, and striatum). Most of the brain areas showed accumulation of
      aluminium, but a greater and more significant increase was noted in the group
      receiving aluminium via intraperitoneal administration. Aluminium distribution
      was also dependent on the administration route.

PMID- 18039494
TI  - Metallothionein functions and structural characteristics.
AB  - Metallothioneins (MTs) are low molecular weight proteins characterized by a high
      cysteine content and give rise to metal-thiolate clusters. Most MTs have two
      metal clusters containing three and four bivalent metal ions, respectively. The
      MT gene family in mammals consists of four subfamilies designated MT-1 through MT
      4. MT-3 is expressed predominantly in brain and MT-4 in differentiating
      stratified squamous epithelial cells. Many reports have addressed MT structure
      and function, but despite the increasing experimental data several topics remain
      to be clarified, and the true function of this elusive protein has yet to be
      disclosed. Owing to their induction by a variety of stimuli, MTs are considered
      valid biomarkers in medicine and environmental studies. Here, we will discuss
      only a few topics taken from the latest literature. Special emphasis will be
      placed on MT antioxidant functions, the related oxidation of cysteines, which can
      give rise to intra/intermolecular bridges, and the relations between MTs and
      diseases which could be originated by metal dysregulation.

PMID- 18039495
TI  - Trace elements in growth: iodine and selenium status of Turkish children.
AB  - Starting from the fetal life and increasing the need throughout the childhood,
      adequate intake of micronutrients is of great importance for the proper
      development of structure and function of the body, and the well being. However,
      micronutrient deficiency is widespread in many populations of the world mainly
      due to nutritional insufficiencies and/or inadequate and unbalanced nutrition.
      While iodine and selenium (Se) are inadequately available for men and live stock
      in many parts of the world, Turkey is one of those countries where iodine
      deficiency (ID) is widespread, Se levels are marginal. In this communication,
      importance of adequate iodine and Se nutrition and status of Turkish children is
      summarized.

PMID- 18039496
TI  - Trace element requirements in critically ill burned patients.
AB  - Critically ill burned patients are characterized by a strong oxidative stress, an
      intense inflammatory response, and months-long hypermetabolism, all of which are
      proportional to the severity of injury. Trace element (TE) deficiencies have
      repeatedly been described. The clinical course is complicated by organ failures,
      infections, and delayed wound healing, which can be partly attributed to TE
      deficiencies. Among critically ill patients, TE deficiencies are the most severe
      in major burns, who suffer a specific copper deficiency. Plasma TE concentrations
      are low during any critical illness, as a result of TE losses in biological
      fluids, low intakes, dilution by fluid resuscitation, and redistribution from
      plasma to tissues mediated by the inflammatory response. The large exudative
      losses cause negative TE balances. Intravenous supplementation trials show that
      early substitution improves recovery, reduces infectious complications
      (particularly nosocomial pneumonia), normalize thyroid function, normalize skin
      tissue levels, improve wound healing and shorten hospital stay. Nevertheless,
      prolonged high dose delivery may be deleterious, as TE have potential for
      toxicity. In major burns, supplements up to 4 mg of Cu/day, 500 mcg [DOSAGE ERROR
      CORRECTED] Se/day and 40 mg Zn/day for 3 weeks have been found to be safe and
      effective. The intravenous route appears the only way to deliver the doses
      required to achieve antioxidant and clinical effects. Further research is
      required to determine the optimal combination and doses for different severities
      of injury.

PMID- 18039497
TI  - Updating of normal levels of copper, zinc and selenium in serum of pregnant
      women.
AB  - Selenium, copper and zinc status is important in pregnant women. The aim of this
      study was to establish updated normal ranges for these elements in serum of
      pregnant women from the Spanish region of Aragon, and to study variation in
      levels with respect to gestational period and maternal age. The study group
      consisted of 159 pregnant women who did not suffer from serious pathologies.
      These samples were classified into four gestational-period groups. Zn and Cu
      determinations were obtained by flame atomic absorption spectroscopy in a Perkin
      Elmer 1100B apparatus, and Se was determined by electrothermal atomic absorption
      spectrometry with Zeeman correction, in a Perkin-Elmer 4110 ZL apparatus. The
      concentrations of Cu, Zn and Se averaged 73.61+/-43.67 microg/dL, 65.37+/-12.87
      microg/dL and 99.59+/-21.74 microg/L, respectively. The Cu/Zn ratio increased
      from first trimester to the third trimester (2.07-3.49). There was no significant
      correlation between Zn and Se levels, but a significant correlation was found
      between Cu and Se levels (p<0.05) and between Cu and Zn levels (p<0.001). Serum
      Zn and Se levels decreased over gestation, while serum Cu concentrations
      increased; in all cases the variation occurred mostly in the first 3 or 4 months,
      with mean levels then remaining fairly stable until the end of pregnancy.
      Maternal age did not influence levels of any of the three metals.

PMID- 18039498
TI  - Effects of angiotensin-converting enzyme inhibitors (ACE i) on zinc metabolism in
      patients with heart failure.
AB  - The aim of this study is to investigate the effects of angiotensin-converting
      enzyme (ACE) inhibitors and furosemide on zinc metabolism by assessing serum zinc
      and urine levels in hospitalized subjects. We recruited 11 patients with heart
      failure from the Internal Medicine Department; these patients had been
      hospitalized less than 72 h before. Heart failure was defined using clinical and
      radiological signs. Serum zinc concentrations were measured using an
      air/acetylene flame atomic absorption spectrophotometer. Urine zinc levels were
      analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Data were
      obtained from the 11 patients and 24 healthy controls matched for age and sex.
      Results indicate higher urine zinc levels and lower concentrations of zinc in
      serum in heart failure patients vs matched controls (p<0.05). This study suggests
      that treating heart failure patients with ACE inhibitors may result in zinc
      deficiency.

PMID- 18039499
TI  - Bioelement effects on thyroid gland in children living in iodine-adequate
      territory.
AB  - Endemic goitre is a primary pathology of thyroid gland and critical medico social
      problem in many countries. A dominant cause of endemic goitre is iodine
      deficiency. However, besides primary iodine deficiency, the goitre may probably
      develop due to effects of other bioelement imbalances, essential to thyroid
      function maintenance. Here we studied 44 cases of endemic goitre in prepubertal
      children (7-10 y.o.) living in iodine-adequate territory. Thyroid volume was
      estimated by ultrasonometry. Main bioelements (Al, Ca, Cd, Co, Cr, Cu, Fe, Hg, I,
      Mg, Mn, Pb, Se, Si, Zn) were determined in hair samples by ICP-OES/ICP-MS method.
      Relationships between hair content of bioelements and thyroid gland size were
      estimated by multiple regressions. The regression model revealed significant
      positive relations between thyroid volume and Cr, Si, Mn contents. However, the
      actual factor of thyroid gland increase was only Si excess in organism.
      Significant negative relations of thyroid volume were revealed with I, Mg, Zn,
      Se, Co and Cd. In spite of this, the actual factors of thyroid gland volume
      increasing were I, Co, Mg and Se deficiency. Total bioelement contribution in
      thyroid impairment was estimated as 24%. Thus, it was suggested that endemic
      goitre in iodine-adequate territory can be formed by bioelement imbalances,
      namely Si excess and Co, Mg, Se shortage as well as endogenous I deficiency in
      spite of iodine-adequate environment.

PMID- 18039500
TI  - Hair trace element contents in women with obesity and type 2 diabetes.
AB  - During 2003-2006 totally 1470 women 46-60 y.o., living mainly in Moscow city and
      Moscow region, were observed. There were three groups of women: obese, diabetic
      and practically healthy. The anthropometric and clinical data were compared with
      elemental status, estimated by atomic emission and mass spectroscopy with
      inductively coupled plasma (ICP-AES/ICP-MS) analyses of occipital scalp hair. The
      obesity in women was corresponding to elevated hair K, Hg, Pb and decreased Ca,
      Mg, Zn, I. The type 2 diabetes was corresponding to elevated hair K, Na, Hg and
      decreased Ca, Mg, Zn, Co. So, the obtained data demonstrate the very similar
      changes in hair elemental content in both obese and diabetic women, thus
      suggesting the general pathophysiological mechanisms of metabolic mineral
      disturbances.

PMID- 18039501
TI  - Effects of high doses of selenium, as sodium selenite, in septic shock patients a
      placebo-controlled, randomized, double-blind, multi-center phase II study-
      selenium and sepsis.
AB  - Selenium has a double action. (i) Seleno-compounds, among them sodium selenite
      have a direct pro-oxidant action leading to acute toxicity but may be also
      beneficial as drug. (ii) Selenium is an essential anti-oxidant required for anti
      oxidant seleno-enzymes. Septic shock is a common severe syndrome leading to
      endothelium damage and multiple organ failure, with increased data suggesting the
      principle role of oxidative stress. Selenoprotein P, main selenium constituent of
      the plasma, may decrease dramatically and specifically in septic shock patients
      and may be involved in the endothelium protection. A prospective, multi-center
      placebo-controlled, randomized, double-blind study in severe septic shock
      patients with documented infection has been preformed. Patients received, for 10
      days, selenium as sodium selenite (4000 microg on the first day, 1000 microg/day
      on the 9 following days) or matching placebo using continuous intravenous
      infusion. Mortality rates did not significantly differ between groups at any time
      point. Adverse events rates were similar in the two groups. However, high-dose
      selenium administration has been associated with a tendency to decrease the
      mortality in septic shock animal and patients, especially when using a bolus
      administration, whereas studies using a continuous administration failed to find
      any benefit on mortality. The interest of the successive use of pro-oxidant
      action of seleno-compounds, followed by anti-oxidant action need to be the
      further studied in cellular and animal models, preceding new dose-effect phase
      II. The interest of the selenoprotein-P as a marker of septic shock and for
      endothelium protection needs also to be studied further.

PMID- 18039502
TI  - Relationships between selenium, lipids, iron status and hormonal therapy in women
      of the SU.VI.M.AX cohort.
AB  - Significant differences in serum selenium concentration according to
      contraceptive treatment and age have been evidenced in women of the SU.VI.M.AX
      cohort. This study aimed at verifying the physiopathological hypothesis that the
      observed increase in serum selenium concentration could be related to serum lipid
      increase and/or bleeding decrease. Women were divided into six groups: menopausal
      with or without hormonal replacement therapy; non-menopausal using contraceptive
      pills; intrauterine device; other contraceptive treatment or no contraceptive
      treatment. Adjusted linear regression indicated positive associations between
      selenium and apolipoprotein A1 (r(2) from 0.038 to 0.074, p<0.07 depending on
      groups) or ferritin in serum (r(2) from 0.032 to 0.075, p<0.07 depending on
      groups). These relationships could explain the differences observed according to
      hormonal treatment and age in the SU.VI.MAX study.

PMID- 18039503
TI  - Trace element contents in serum of healthy elderly population of metropolitan Sao
      Paulo area in Brazil.
AB  - In this study, the elements Br, Ca, Cl, Fe, Na, Rb, Se and Zn were determined in
      serum of a healthy elderly population residing in the Sao Paulo Metropolitan
      area, using instrumental neutron activation analysis. Comparison studies
      indicated that only Se concentration was significantly lower in the elderly group
      aged 75-91 years than those obtained for the group aged 60-74 years. Between
      genders, males presented lower Br concentrations and, the females lower Fe. Mean
      concentrations obtained for most elements were within the values reported in the
      literature.

PMID- 18039504
TI  - The sister chromatide exchange rate is inversely related to the Se, Sr, Mn, Cu,
      and Be trace element nutritional status.
AB  - We studied the relationship of the 39 whole blood trace elements and the
      peripheral lymphocyte sister chromatide exchange (SCE) by factor analysis. Se,
      Sr, Mn, Cu, and Be were inversely related to SCE, and hence protective against
      the free radicals.

PMID- 18039505
TI  - Definitions and principles for bioindication and biomonitoring of trace metals in
      the environment.
AB  - Clear-cut definitions are given for most terms used in monitoring studies. In
      these studies the observation or experimental investigation of living organisms
      give a qualitative or quantitative information on the state of the environment
      with special reference to trace metals. The focus and future goals of
      biogeochemical research must consider the direct effects on human health, by
      including modelling of active biogeochemical processes than they have done so
      far. Newly developed strategies as the multi-markered bioindication concept
      (MMBC) with its functional and integrated windows on prophylactic healthcare are
      essential tools for successfully observing the environment with respect to trace
      metals. An intensified training of students and a strong hand in hand work
      between industrial, educational and public institutions is necessary.

PMID- 18039506
TI  - Physiologically based extraction of heavy metals in compost: preliminary results.
AB  - A physiologically based extraction test (PBET) was run for the extraction of six
      metals (Cu, Zn, Cd, Cr, Ni and Pb) in four composts containing high
      concentrations of heavy metals. An aqueous solution of pepsin plus citric,
      acetic, and malic acids buffered to pH 2 was used to simulate the gastric
      mixture, and an extraction of 1h at 37 degrees C was run with a solid:liquid
      ratio of 1:100. The results were compared to those obtained using water and
      CaCl(2)-DTPA solution. The PBET extracted far more metals than water, but less
      than CaCl(2)-DTPA for Cu, Pb and Cr, while giving similar or slightly lower
      results for Cd, Zn, and Ni.

PMID- 18039507
TI  - Reflections on safety in perianesthesia settings.

PMID- 18039508
TI  - An Introduction to the ASPAN Position Statement on Perianesthesia Safety.

PMID- 18039509
TI  - Development and initial testing of the perianesthesia safe practices instrument:
      an ASPAN pilot study.
AB  - The perianesthesia environment of care is a unique high-risk health care setting
      that has a high susceptibility to error because of the vulnerability of patients
      who are undergoing surgery and anesthesia as well as the high levels of activity
      in these units. Safe practice in this environment is essential to quality patient
      care and positive patient outcomes. Consequently, ASPAN conducted a descriptive
      cross-sectional pilot study to test initial reliability and validity of the
      Perianesthesia Safe Practices Survey Instrument. The instrument was designed to
      assess specific safe practices in perianesthesia areas by identifying the
      following: (1) what are the current perianesthesia safety practices, (2) what are
      the recommended safety practices that are not in place, and (3) what are the
      differences in safety practices within areas along the perianesthesia continuum
      of care. Thirty-six respondents found the instrument to be clear, easy to
      complete, and containing appropriate content. The alpha coefficients for internal
      consistency for the unit specific components were preadmission testing (.79), pre
      op (.94), Phase I PACU recovery (.92), and Phase II PACU recovery (.90). The
      results of this pilot study provided information about areas of excellence and
      areas for improvement for safe clinical practice in the specialty setting, as
      well as initial reliability and validity for the safe practices questionnaire.

PMID- 18039510
TI  - Patient safety: perianesthesia nursing's essential role in safe practice.
AB  - A safety culture that promotes best practices and best outcomes is important in
      today's healthcare environment. The perianesthesia environment of care is
      constantly challenged with the introduction of new technologies, improved
      medications, and advances in surgical and nonsurgical procedures. This practice
      is also marked by fast turnover, increasing volume, and, often, high-acuity
      patients. The integration of principles of safety and evidence-based principles
      is a core value of perianesthesia practice. The American Society of
      PeriAnesthesia Nurses (ASPAN) is committed to providing the foundation to support
      a culture of perianesthesia safety. This article will discuss the development of
      the ASPAN Safety Model by the ASPAN Safety Committee.

PMID- 18039511
TI  - Safe staffing for the post anesthesia care unit: weighing the evidence and
      identifying the gaps.
AB  - Postanesthesia nursing care and standards are continually evolving. ASPAN has the
      professional responsibility to develop standards of nursing practice to promote a
      safe environment of care. Currently, ASPAN's recommended staffing ratios are
      based on the best available evidence: expert opinion and consensus. Our Society
      believes that these nurse-to-patient ratios have served to provide safe, quality
      patient care. In 2006, the ASPAN Safe Staffing Strategic Work Team was charged
      with conducting a national PACU Safe Staffing Evidence-Based Practice (EBP)
      project. The purpose of this EBP staffing project was to search the scientific
      staffing evidence in an attempt to validate ASPAN's staffing ratios. This expert
      panel critically weighed the nursing evidence on staffing ratios, workload
      intensity, patient acuity, nursing-sensitive outcomes, and nursing-sensitive
      indicators, including appropriate critical care studies because of the scarce
      number of postanesthesia studies. The outcome of this dynamic initiative revealed
      the need to develop nursing-sensitive perianesthesia indicators that can provide
      patient outcomes used to assess the effectiveness of staffing ratios. Finally,
      research gaps were identified and the next steps in the generation of knowledge
      needed to build safe staffing evidence were identified in ASPAN's Strategic
      Research Staffing Plan.

PMID- 18039512
TI  - Factors affecting incident reporting by registered nurses: the relationship of
      perceptions of the environment for reporting errors, knowledge of the nursing
      practice act, and demographics on intent to report errors.
AB  - Patient safety has assumed an international focus. In the past, the focus on
      detecting and preventing errors was up to the individual clinician, often the
      registered nurse. With impetus from the Institute of Medicine and other national
      agencies, a shift to emphasis on systems and processes and near miss and error
      reporting has occurred. Information from caregiver reporting has taken on new
      importance. This study was conducted to explore nurses' willingness to report
      errors of varying degrees of severity and the factors that impacted that intent.
      Registered nurses were selected randomly from the Texas Board of Nurse Examiners'
      roster and surveyed regarding perceptions of the environment for reporting,
      perceptions of reasons for not reporting, knowledge of the nursing practice act,
      and demographic variables. A majority of nurses were willing to report all levels
      of errors. Primary position, reasons for not reporting, and years since initial
      licensure were predictors of intent to report incidents with no injury and those
      with minimal injury. All but four nurses (99%) indicated that they would report
      incidents resulting in moderate to severe injury or death.

PMID- 18039513
TI  - Medication errors in the PACU.
AB  - A collaborative research group examined seven years of PACU medication errors
      from the MEDMARX database. Descriptive statistics showed a comparison of
      medication errors in all ages from pediatric to adult to geriatric groups. Nine
      categories of medication errors were noted and a total of 3,023 errors were
      attributed to errors in prescribing, transcribing, dispensing, administering, and
      monitoring. Harmful errors were present in 5.8% of the sample, which included two
      patient deaths. Results indicated that errors can occur in any age group.
      Organizations and institutions should be aware of these occurrences to ensure
      vigilance at all times and to focus efforts toward avoiding or decreasing such
      errors. Patient safety and error prevention recommendations are provided.

PMID- 18039514
TI  - Keeping our nurses and patients safe.

PMID- 18039515
TI  - In the beginning...the origin and evolution of ASPAN's Perianesthesia Data
      Elements.

PMID- 18039516
TI  - Fatigue: when the "little engine that could" just can't anymore!

PMID- 18039517
TI  - High-alert medications in the perioperative setting.

PMID- 18039518
TI  - The Joint Commission's Speak Up Initiative.

PMID- 18039519
TI  - Patient safety: nursing priority.

PMID- 18039520
TI  - Improvement but no cure of left ventricular systolic dysfunction in treated heart
      failure patients.
AB  - BACKGROUND: Recent advances in pharmacological and pacemaker-based treatments for
      heart failure (HF) have brought about significant improvements in left
      ventricular function. AIMS: To identify the proportion of treated systolic HF
      patients in whom left ventricular systolic function improves and/or returns to
      normal. METHODS: This was a retrospective analysis of 221 HF patients.
      Improvement in left ventricular function was defined as an improvement in
      ejection fraction (LVEF) of > or =10% on echocardiography. Return to normal was
      defined as an improvement of LVEF to > or =50% and a reduction in left
      ventricular end diastolic diameter to < or =55 mm. Changes in BNP were also
      recorded. RESULTS: Improvement in LVEF was observed in 44.3% of patients and
      return to normal systolic function in 10.9%, only 2.3% had both a return to
      normal echocardiographic parameters and a BNP<100 pg/ml. A higher percentage of
      the improved group were on target doses of beta-blockers (p=0.004). Baseline BNP
      was not a predictor of improvement. There was a trend towards a reduction in HF
      readmissions in the improved group (p=0.07) but no difference in the risk of
      death or all-cause readmission. CONCLUSION: While a substantial proportion of
      treated HF patients have an improvement in left ventricular function over time,
      only a small proportion return to normal dimensions and LVEF, underlining the
      permanent nature of ventricular damage in the vast majority of patients.

PMID- 18039521
TI  - A journey with Tony Hugli up the inflammatory cascade towards the auto-digestion
      hypothesis.
AB  - My association with Tony Hugli, long-term editor of Immunopharmacology and
      International Immunopharmacology, came about by a specific and long-standing
      problem in inflammation research. What is the trigger mechanism of inflammation
      in physiological shock? This is an important clinical problem due to the high
      mortality associated with physiological shock. We joined forces in the search of
      the answer to this question for more than a decade. Our journey eventually led to
      development of the hypothesis that shock may be associated with pancreatic
      enzymes, a set of powerful digestive enzymes that are an integral part of human
      digestion. The digestive enzymes need to be compartmentalized in the lumen of the
      intestine where they break down a broad spectrum of biological molecules into
      their building blocks, suitable for molecular transport across the mucosal
      epithelium into the circulation. The mucosal epithelial barrier is the key
      element for compartmentalization of the digestive enzymes. But under conditions
      when the mucosal barrier is compromised, the fully activated digestive enzymes in
      the lumen of the intestine are transported into the wall of the intestine,
      starting an auto-digestion process. In the process several classes of mediators
      are generated that by themselves have inflammatory activity and upon entry into
      the central circulation generate the hallmarks of inflammation and eventually
      cause multi-organ failure. Thus, our journey led to a new hypothesis, which is
      potentially of fundamental importance for death by multi-organ failure. The auto
      digestion hypothesis is in line with the century old observation that the
      intestine plays a special role on shock - indeed it is the organ for digestion.
      Auto-digestion may be the prize to pay for life-long nutrition.

PMID- 18039522
TI  - Comparative study to elucidate the mechanism underlying the difference in airway
      hyperresponsiveness between two mouse strains.
AB  - The mechanism underlying airway hyperresponsiveness (AHR), a characteristic
      feature of asthma, remains obscure. We attempted to elucidate the mechanism
      responsible for the different degrees of AHR in two mouse strains, BALB/c and
      C57BL/6, following exposure to an anaphylactic trigger. When ovalbumin (OVA)
      sensitized mice were challenged daily with OVA for up to three consecutive days,
      the BALB/c mice showed a higher degree of airway responsiveness to methacholine
      than did C57BL/6. Following the OVA challenge, eosinophils and macrophages in
      bronchoalveolar lavage fluid (BALF) from BALB/c increased significantly in number
      compared to those from C57BL/6. BALB/c mice also exhibited a higher serum IgE
      level than that of C57BL/6 after OVA challenge. The enhanced AHR and eosinophilic
      infiltration in BALF were significantly reduced by pretreatment with a selective
      cysteinyl-leukotriene type 1 receptor (cysLT(1)R) antagonist, montelukast. In the
      in vitro study, cysLT production was significantly lower in the dissected lung
      tissue from BALB/c than in tissue from C57BL/6 when both groups were stimulated
      with saline. The lungs from BALB/c generated significantly larger amounts of
      cysLTs on incubation with OVA rather than with saline, while the lungs from
      C57BL/6 did not show any significant increase in cysLTs with antigen stimulation.
      Significant upregulation of cysLT(1)R and cysLT(2)R mRNA expression was induced
      by OVA challenge in the lungs of BALB/c, but not in those of C57BL/6. It is
      suggested that, after an anaphylactic reaction, the degree of AHR is dependent on
      the genetic background and that cysLTs play an important role in the mechanism
      involved.

PMID- 18039523
TI  - Comparison of kinin B(1) and B(2) receptor expression in neutrophils of asthmatic
      and non-asthmatic subjects.
AB  - Kinins have been implicated in the pathophysiology of asthma and activation of
      kinin receptors stimulates neutrophil chemotaxis. However, the expression of
      kinin receptors on neutrophils of asthmatic subjects has not been assessed. The
      aim of this study was to compare the expression of kinin B(1) and B(2) receptor
      mRNA and proteins in neutrophils of asthmatic and non-asthmatic subjects, and to
      assess whether inhaled corticosteroid treatment may influence expression of the
      kinin receptors. Neutrophils were isolated from peripheral blood of asthmatic
      (n=27) and non-asthmatic subjects (n=14). The presence of kinin B(1) and B(2)
      receptor protein on neutrophils was confirmed by immunolabeling with specific
      antibodies followed by immunoperoxidase, immunofluorescence and FACS detection.
      Kinin B(1) and B(2) receptor mRNA expression was assessed by RT-PCR. Quantitative
      image analysis of fluorescence immunolabeled neutrophils showed no differences in
      kinin B(1) or B(2) receptor protein expression between asthmatic and non
      asthmatic subjects. Similarly, quantitative real time RT-PCR analysis
      demonstrated no differences in expression of mRNA for the kinin B(1) or B(2)
      receptors between asthmatic and non-asthmatic subjects. However, B(1) receptor
      mRNA expression was significantly lower in asthmatic subjects using > or =2000
      microg of inhaled corticosteroid per day (p<0.05) and B(1) receptor protein
      levels also tended to be lower in these subjects. Corticosteroids may have a
      beneficial anti-inflammatory effect in asthma by down-regulating B(1) receptor
      expression on neutrophils, thereby decreasing the migration of these inflammatory
      cells into the airways.

PMID- 18039524
TI  - Trapping of adrenergic decongestant drugs into cellular endomembrane
      compartments: toxicological and pharmacological consequences.
AB  - Rhinitis of allergic and viral origin is often self-treated by patients with
      locally applied vasoconstrictor decongestant drugs. In turn, prolonged use of
      these agents produce an inflammatory condition termed rhinitis medicamentosa.
      Cationic drugs are sequestered into cells via various mechanisms, including
      mitochondrial concentration and V-ATPase-driven trapping in vacuoles that swell
      by an osmotic mechanism. We hypothesized that receptor-independent endomembrane
      sequestration of topically applied concentrated alpha-adrenoceptor agonists
      (decongestants, mydriatics) could contribute to their toxicity and prolonged
      duration of action. The morphological and functional effects of phenylephrine and
      xylometazoline on rabbit aortic smooth muscle cells were examined and their
      possible sequestration evaluated using the contractility of rabbit aorta rings.
      Synthetic agonists produced V-ATPase-dependent cell vacuolization (prevented by
      bafilomycin A1; xylometazoline 250 microM, phenylephrine 2.5 mM). V-ATPase
      mediated cytotoxicity was slow (24 h; phenylephrine only, 5-10 mM); a rapid
      xylometazoline-induced cytotoxicity (> or =500 microM, 4 h) correlated to
      mitochondrial functional alterations. Xylometazoline had slower contraction and
      relaxation kinetics than the other alpha-adrenoceptor agonists in the aorta;
      bafilomycin pre-treatment influenced its kinetics (accelerated contraction and
      relaxation) and concentration-effect relationship (potentiation). V-ATPase-driven
      sequestration contributed to a component of the tissue reservoir of both
      phenylephrine and xylometazoline as assessed by aortic rings contracted with the
      concentrated agonists and subsequently washed. Phenylephrine and xylometazoline
      caused the V-ATPase-dependent cytopathology at a fraction of the usual topical
      concentrations; this form of sequestration influenced the toxicity and
      pharmacology of individual agents.

PMID- 18039525
TI  - Double-stranded RNA increases kinin B1 receptor expression and function in human
      airway epithelial cells.
AB  - Increased levels of kinins have been detected within the airways during upper
      respiratory viral infections (URIs). Rhinovirus, the major URI associated with
      acute exacerbations of asthma, is an ssRNA virus that primarily infects the
      airway epithelium and produces dsRNA during replication. We asked whether dsRNA
      could increase the expression of kinin receptors in airway epithelial cells,
      thereby potentiating the inflammatory consequences of kinin generation. Human
      airway epithelial cell line BEAS-2B was stimulated with the dsRNA analog Poly I:C
      and kinin receptor expression detected by quantitative RT-PCR as well as
      radioligand binding. Poly I:C induced an increase in B1 and B2 receptor mRNA
      levels in BEAS-2B and primary human normal bronchial epithelial cells. At the
      cell surface, only B1 receptor expression was increased by Poly I:C. Furthermore,
      pretreatment of BEAS-2B cells with Poly I:C enhanced the induction of phospho-ERK
      following B1 receptor ligand stimulation. To investigate whether these finding
      had potential in vivo relevance, we assessed B1 receptor expression in nasal
      tissue obtained from 8 normal human subjects with URIs and 3 control subjects.
      Five of the URI subjects demonstrated increased B1 receptor mRNA compared to the
      3 control subjects. We suggest that increased expression of B1 receptor in the
      human airway following a URI could increase the risk of an exacerbation of asthma
      by contributing to increased inflammation in the airway.

PMID- 18039526
TI  - Structure and function of human plasma carboxypeptidase N, the anaphylatoxin
      inactivator.
AB  - Human carboxypeptidase N (CPN) was discovered in the early 1960s as a plasma
      enzyme that inactivates bradykinin and was identified 8 years later as the major
      "anaphylatoxin inactivator" of blood. CPN plays an important role in protecting
      the body from excessive buildup of potentially deleterious peptides that normally
      act as local autocrine or paracrine hormones. This review summarizes the
      structure, enzymatic properties and function of this important human enzyme,
      including insights gained by the recent elucidation of the crystal structure of
      the CPN catalytic subunit and structural modeling of the non-catalytic regulatory
      83 kDa subunit. We also discuss its physiological role in cleaving substrates
      such as kinins, anaphylatoxins, creatine kinase, plasminogen receptors,
      hemoglobin and stromal cell-derived factor-1alpha (SDF-1alpha).

PMID- 18039527
TI  - Active monomers of human beta-tryptase have expanded substrate specificities.
AB  - beta-Tryptase, a product of the TPSAB1 and TPSB2 genes, is a trypsin-like serine
      protease that is a major and selective component of the secretory granules of all
      human mast cells, accounting for as much as 25% of cell protein. Once mast cells
      are activated, beta-tryptase is released along with histamine and heparin
      proteoglycan. beta-Tryptase is a unique enzyme with a homotetrameric structure in
      which active sites face into the central cavity of the four monomers, stabilized
      by heparin-proteoglycan. This structure makes beta-tryptase resistant to most
      biological inhibitors of serine proteases. Without stabilization, at neutral pH
      beta-tryptase converts to inactive monomers. Tryptase levels are elevated in
      bronchoalveolar lavage (BAL) fluid obtained from atopic asthmatics and in serum
      during systemic anaphylactic shock. Several synthetic small molecular weight beta
      tryptase inhibitors reduced Ag-induced airway hypersensitivity in animals,
      suggesting that beta-tryptase is involved in the pathogenesis of airway
      inflammation. Although the major biologic substrate(s) of beta-tryptase remain
      ambiguous, the protease can digest several proteins of potential biologic
      importance, including fibrinogen, fibronectin, pro-urokinase, pro-matrix
      metalloprotease-3 (proMMP-3), protease activated receptor-2 (PAR2) and complement
      component C3. Recently, monomers of beta-tryptase with enzymatic activity have
      been detected in vitro. Here we discuss how beta-tryptase monomers with enzymatic
      activity were identified as well as their potential role in vivo.

PMID- 18039528
TI  - The role of the complement anaphylatoxins in the recruitment of eosinophils.
AB  - Eosinophils are blood and tissue immune cells that participate in a diverse range
      of activities normally beneficial for the host defense, but in circumstances of
      untoward inflammatory conditions these cells can be responsible for pathological
      responses. Accordingly the transit of eosinophils from the blood to tissues is a
      subject of considerable importance in immunology. In this article we review how
      the complement anaphylatoxins, C3a and C5a bring about eosinophil extravasation.
      These mediators do not merely provide a chemotactic or haptotactic gradient but
      are responsible for orchestrating innumerable responses by other cells types,
      including of endothelial cells, mast cells, and basophils in order to create an
      environment that is conducive for eosinophil infiltration. C5a has the capacity
      to prime the endothelium directly to present P-selectin, and C5a stimulated
      generation of eosinophil hydrogen peroxide and other oxidants can cause
      additional upregulation of endothelial P-selectin and ICAM-1. Moreover, the
      anaphylatoxins have the ability to recruit mast cells and basophils and can
      stimulate these cells to release IL-4 and IL-13, which by augmenting endothelial
      VCAM-1, convey some selectivity for eosinophils. The anaphylatoxins also have the
      capability to evoke the release and activation of eosinophil MMP-9, which is
      employed by this cell type to digest its way past the subendothelial matrix.
      Finally, because C3a and C5a can stimulate the generation of nitric oxide along
      with the secretion of histamine and LTC4 from several cell types, the
      anaphylatoxins can bring about an increase in vascular permeability that
      facilitates eosinophil accumulation at sites of allergic inflammation.

PMID- 18039529
TI  - Physiological concentrations of transforming growth factor beta1 selectively
      inhibit human dendritic cell function.
AB  - In this study the effects of different in vitro conditioning with transforming
      growth factor (TGF) beta1 on human monocyte-derived DC maturation (hMo-DC) were
      investigated. hMo-DC differentiated in the presence of physiologically relevant
      concentrations of TGFbeta1 (2 ng/ml) failed to undergo complete maturation
      despite adequate stimulation with LPS or LPS+IFNgamma. These hMo-DC did not
      produce IL-12p70 or PGE2, and showed decreased IL-10 and IL-18 production and HLA
      DR expression. However, the expression of these molecules, except for IL-12p70,
      was not significantly affected in hMo-DC differentiated in the presence of lower
      concentrations of TGFbeta1 (0.2 and 0.02 ng/ml). Exposure of hMo-DC to TGFbeta1
      (2 ng/ml) after they had completed differentiation had minimal effects. Thus, the
      functional response of hMo-DC to LPS or LPS+IFNgamma depended on the stage of hMo
      DC differentiation at which cells were first exposed to TGFbeta1 and on the
      concentration of TGFbeta1. These results suggest that in the in vivo micro
      environment, the concentrations and the timing of monocyte exposure to TGFbeta1
      may be crucial in the differentiation of DC toward more or less mature
      phenotypes, and this may have important implications for DC functions. The
      decrease in T-cell proliferation and a small increase in IL-5 production by T
      cells co-cultured with hMo-DC that had been treated with TGFbeta1, suggest the
      possibility that in vivo such DC may provide chronic, but incomplete signals to T
      cells, and this could be a potential mechanism underlying polarisation of T cells
      towards anergy.

PMID- 18039530
TI  - Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and
      pleura: therapeutic targets.
AB  - Cancers of the lung and pleura remain a major cause of cancer deaths, both in men
      and women, with strong causal relationships between cigarette smoking and
      asbestos fibres, and deaths from lung cancer and mesothelioma, respectively. The
      poor survival rates for small cell lung cancer and mesotheliomas argue powerfully
      for greater understanding of mechanisms of carcinogenesis, genetic abnormalities
      and the role of tumour suppressor genes and proteins in carcinomas of the lung
      and pleura. Despite progress in the development of newer cytotoxic drugs, lung
      cancer remains a lethal disease. Chemotherapy and radiotherapy produce only a
      modest improvement in survival of patients with advanced disease. Increased
      knowledge of molecular mechanisms of lung cancer and apoptosis are providing
      opportunities for treating lung cancer with new classes of molecularly targeted
      drugs. These novel therapies should target the abnormalities in lung cancer by
      maximizing the effects of anti-tumour molecules, with minimal side effects on
      normal tissues. Of the several molecular targets, those receiving attention are
      p53 gene replacement, Bcl-2 downregulation, apoptosis by induced by TNF, the
      FAS/CD95 receptor system and TRAIL, and inhibition of NF-kappaB. Although several
      studies have shown benefits, there is a need for well planned clinical trials of
      drugs that target the apoptotic cascade. Stem cell therapy and gene replacement
      offer the prospect of novel approaches that are likely in the near future to play
      a definitive role in the treatment of advanced lung cancer. Furthermore, with
      their apparent minimal toxicity to normal tissues, the newer molecular targets
      represent attractive investigational directions for innovative cancer therapies.

PMID- 18039531
TI  - Applying genomics to organ transplantation medicine in both discovery and
      validation of biomarkers.
AB  - The field of biomarker discovery made a significant leap over the past few
      decades. As we enter the Era of the Human Genome, thousands of biomarkers can be
      identified in a relatively high-throughput fashion. While such magnitude and
      diversity of biomarkers can be seen as a challenge by itself, the field is being
      moved forward by new advances in bioinformatics and Systems Biology. Because of
      the life and death nature of end stage organ failure that transplantation treats,
      the severe donor organ shortage, and the powerful and toxic drug therapies
      required for the lifetimes of transplant patients, we envision a future for
      biomarkers as tools to diagnose disease in its early stages, predict prognosis,
      suggest treatment options and then assist in the implementation of therapies. By
      harnessing the power of multiple technologies in parallel makes it possible to
      discover and then validate the next generation of biomarkers for transplantation.
      We see the road ahead diverge into two paths: one from biomarkers to diagnosis
      and therapy and the other to a new level of insight into the complex molecular
      networks that determine when a healthy state becomes diseased and dysfunctional.

PMID- 18039532
TI  - The structure of the O-specific polysaccharide of the lipopolysaccharide from
      Pantoea agglomerans strain FL1.
AB  - A neutral O-specific polysaccharide consisting of d-rhamnose was obtained by mild
      acid hydrolysis of the lipopolysaccharide of the plant pathogenic bacterium
      Pantoea agglomerans strain FL1, a common epiphyte of many plant species, and
      associated with Pseudomonas savastanoi pv. savastanoi in young and apparently
      intact olive knots. By means of compositional and methylation analyses, and NMR
      spectroscopy, the chemical repeating unit of the polymer was identified as a
      linear tetrasaccharide of the structure:

PMID- 18039533
TI  - Acid-catalysed rearrangement of glycosyl trichloroacetimidates: a novel route to
      glycosylamines.
AB  - A novel route to glycosylamines has been developed. Treatment of glycosyl
      trichloroacetimidates with TMSOTf under glycosylation conditions, but in the
      absence of an acceptor, resulted in complete rearrangement of the
      trichloroacetimidates into the corresponding N-protected-glycosylamines.
      Reductive cleavage of the trichloroacetyl groups using sodium borohydride
      provided the desired glycosylamine products.

PMID- 18039534
TI  - Synthesis and geometry of methyl (methyl 4-O-acetyl-3-azido-2,3-dideoxy
      alpha/beta-D-arabino- and -alpha/beta-D-ribo-hexopyranosid)uronates.
AB  - The synthesis of methyl (methyl 4-O-acetyl-3-azido-2,3-dideoxy-alpha/beta-D
      arabino- and -alpha/beta-D-ribo-hexopyranosid)uronates is presented. High
      resolution (1)H and (13)C NMR spectral data for all diastereoisomers and single
      crystal X-ray diffraction analysis for methyl (methyl 3-azido-2,3-dideoxy-beta-D
      arabino-hexopyranosid)uronate are reported. The planarity of the 4-OAc and 5
      COOMe groups as well as the orientations of the aglycone and azide groups in the
      crystal lattice is discussed. The influence of the 5-COOMe group on the pyranose
      ring conformation is considered.

PMID- 18039535
TI  - Determination of the structure and molecular weights of the exopolysaccharide
      produced by Lactobacillus acidophilus 5e2 when grown on different carbon feeds.
AB  - Lactobacillus acidophilus 5e2 when grown on skimmed milk, skimmed milk
      supplemented with sodium formate and skimmed milk supplemented with glucose
      secretes a branched heteropolysaccharide having a weight average molecular weight
      less than 450 kDa. The exopolysaccharide has a heptasaccharide repeat unit and is
      composed of D-glucose, D-galactose and N-acetyl-D-glucosamine in the molar ratio
      3:3:1. Using chemical techniques and 1D and 2D-NMR spectroscopy the
      polysaccharide has been shown to possess the following repeat unit structure:

PMID- 18039536
TI  - Characterization of the lipopolysaccharide from a wbjE mutant of the serogroup
      O11 Pseudomonas aeruginosa strain, PA103.
AB  - The lipopolysaccharide (LPS) of a wbjE mutant of Pseudomonas aeruginosa PA103, a
      serogroup O11 strain consists of both high and low molecular weight (HMW and LMW)
      LPSs. The HMW LPS consisted exclusively of rhamnan A-band LPS and no B-band LPS
      was detected in the wbjE mutant. Interestingly, the LMW LPS from the wbjE mutant
      showed that it contained a variety of oligosaccharides, each with two or three
      phosphate groups present as mono- or pyrophosphates. These oligosaccharides
      consisted of the complete core octasaccharide. The GalN residue was present as an
      N-acetylated residue in all of these oligosaccharides except the tetrasaccharide
      in which it is present as an N-alanylated residue. None of these oligosaccharides
      contained either a d- or l-FucpNAc residue. These results are discussed with
      regard to the role of wbjE in the biosynthesis of P. aeruginosa PA103 B-band LPS.

PMID- 18039538
TI  - Structural characterization of the acetylated heteroxylan from the natural hybrid
      Paulownia elongata/Paulownia fortunei.
AB  - The heteroxylan from the hybrid Paulownia elongata/Paulownia fortunei is an O
      acetyl-(4-O-methylglucurono)xylan with an acetylation degree (DS) of 0.59 and a
      molecular weight (M(w)) of 29 kDa. The heteroxylan backbone is composed by (1-
      >4)-linked beta-d-xylopyranosyl units (Xylp) partially ramified with terminal (1-
      >2)-linked 4-O-methyl-alpha-D-glucuronosyl (MeGlcpA) and a small proportion of
      alpha-D-glucuronosyl (GlcpA) residues in a molar ratio of Xylp:(MeGlcpA+GlcpA) of
      20:1. Roughly half of the beta-D-xylopyranosyl units in the backbone are
      acetylated: 3-O-acetylated (22 mol %), 2-O-acetylated (23 mol %) or 2,3-di-O
      acetylated (7 mol %). ESI-MS and MALDI-MS studies of partially hydrolyzed
      heteroxylan revealed a random distribution of O-Ac and MeGlcpA within the
      backbone. However, the frequency of substitution with O-Ac along the backbone is
      not uniform and the molecular regions that did not contain MeGlcpA substituents
      possessed an acetylation degree significantly lower than the average DS of the
      xylan.

PMID- 18039537
TI  - A convenient synthesis of the C-1-phosphonate analogue of UDP-GlcNAc and its
      evaluation as an inhibitor of O-linked GlcNAc transferase (OGT).
AB  - The C-1-phosphonate analogue of UDP-GlcNAc has been synthesized using an alpha
      configured C-1-aldehyde as a key intermediate. Addition of the anion of diethyl
      phosphate to the aldehyde produced the hydroxyphosphonate. The configuration of
      this key intermediate was determined by X-ray crystallography. Deoxygenation,
      coupling of the resulting phosphonic acid with UMP and deprotection gave the
      target molecule as a di-sodium salt. This analogue had no detectable activity as
      an inhibitor of (OGT).

PMID- 18039539
TI  - The impact of dilute sulfuric acid on the selectivity of xylooligomer
      depolymerization to monomers.
AB  - The disappearance of xylose and xylooligosaccharides with degrees of
      polymerization (DP) ranging from 2 to 5 was followed at 160 degrees C with
      sulfuric acid added to adjust the pH from near neutral to 1.45, and the impact on
      the yields of lower DP xylooligomers and xylose monomer was determined. In
      addition, the experimental data for the disappearance of these xylooligomers was
      kinetically modeled assuming first-order reaction kinetics for xylose degradation
      and xylooligomer hydrolysis to evaluate how the pH affected the selectivity of
      monomer formation from xylooligomers and direct oligomer degradation to unknown
      products. The yield of xylose from xylooligomers increased appreciably with
      increasing acid concentration but decreased with increasing xylooligomer DP at a
      given acid concentration, resulting in more acid being required to realize the
      same xylose yields for higher DP species. For example, the maximum xylose yields
      were 49.6%, 28.0%, 13.2% and 3.2% for DP values of 2, 3, 4, and 5, respectively,
      at pH 4.75. Kinetic modeling revealed that all the xylooligomers disappeared at a
      higher rate compared to xylose monomer and the disappearance rate constant
      increased with DP at all pH. The kinetics for lower DP oligomers of 2 and 3
      showed that these species directly degrade to unknown compounds in the absence of
      acid. On the other hand, higher oligomers of DP 4 and 5 exhibited negligible
      losses to degradation products at all pH. Therefore, only xylooligomers of DP 2
      and 3 were found to directly degrade to undesired products in the absence of
      acid, but more work is needed to determine how higher DP species behave. This
      study also revealed that the source of water and the material used for the
      construction of the reactor impacted xylose degradation kinetics.

PMID- 18039540
TI  - The applicability of an amidated polysaccharide hydrogel as a cartilage
      substitute: structural and rheological characterization.
AB  - An amidic derivative of a carboxymethylcellulose-based hydrogel was obtained and
      characterized in terms of amidation degree. NMR studies and FT-IR imaging
      spectroscopy demonstrated that the reaction allowed a polymer to be obtained that
      was characterized by a regular distribution of amidic groups along the
      polysaccharide chains. Through this regularity, a homogenous three-dimensional
      scaffold was obtained, which maintained the thixotropic property of the linear
      polysaccharide.

PMID- 18039541
TI  - Indirect approach to C-3 branched 1,2-cis-glycofuranosides: synthesis of aceric
      acid glycoside analogues.
AB  - Aceric acid (3-C-carboxy-5-deoxy-alpha-l-xylofuranose) residues are present in
      pectic polysaccharide rhamnogalacturonan II (RG II) in the form of synthetically
      challenging 1,2-cis-glycofuranosides. To access synthetic fragments of RG II
      incorporating aceric acid, a four-step procedure based on C-2 epimerisation of
      initially prepared 1,2-trans-glycofuranoside was developed. Readily available
      derivatives of branched-chain l-lyxofuranose bearing a 3-C-vinyl group as a
      masked 3-C-carboxyl group were investigated as potential precursors of aceric
      acid units. In the first step of the procedure, installation of a participating
      group at C-2 of the furanose ring ensured stereocontrol of the O-glycosylation,
      which was carried out with the thioglycoside of 2-O-acetyl-3,5-di-O-benzyl-3-C
      vinyl-L-lyxofuranose. After the glycosylation step, the 2-O-acetyl group was
      removed, the free 2-OH group was oxidised and the resulting ketone was finally
      reduced to form the C-3-vinyl-L-xylofuranoside. The use of L-Selectride in the
      key reduction reaction was essential to achieve the required stereoselectivity to
      generate 1,2-cis-furanoside.

PMID- 18039542
TI  - Modulation of lymphocyte function with inhibitory CD2: loss of NK and NKT cells.
AB  - Analysis of the NK cell developmental pathway suggests that CD2 expression may be
      important in regulating NK maturation. To test this hypothesis, we developed mice
      containing only an inhibitory CD2 molecule by linking the extracellular domain of
      CD2 to an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM)
      motif. Mice containing the CD2 Tg(ITIM) transgene, introduced into a CD2 KO
      background, have no morphologically detectable lymph nodes, although development
      of the thymus appears normal. In addition, these mice had major loss of both NK
      and NKT subsets in peripheral organs, while T and B cell frequencies were intact.
      Expression of CD2 was low on T cells and lacking on B cells and functional
      defects were observed in these populations. NKT cells expressing CD4 were absent,
      while the CD8+ and double negative NKT cells were retained. Small subsets of NK
      cells were detected but expression of CD2 on these cells was very low or absent,
      and their maturation was impaired. Based on the phenotype described here, we
      believe that these mice represent a unique model to study lymphoid organ and
      lymphocyte development.

PMID- 18039543
TI  - The role of preschoolers' social understanding in evaluating the informativeness
      of causal interventions.
AB  - Preschoolers use information from interventions, namely intentional actions, to
      make causal inferences. We asked whether children consider some interventions to
      be more informative than others based on two components of an actor's knowledge
      state: whether an actor possesses causal knowledge, and whether an actor is
      allowed to use their knowledge in a given situation. Three- and four-year-olds
      saw a novel toy that activated in the presence of certain objects. Two actors,
      one knowledgeable about the toy and one ignorant, each tried to activate the toy
      with an object. In Experiment 1, either the actors chose objects or the child
      chose for them. In Experiment 2, the actors chose objects blindfolded. Objects
      were always placed on the toy simultaneously, and thus were equally associated
      with the effect. Preschoolers' causal inferences favored the knowledgeable
      actor's object only when he was allowed to choose it (Experiment 1). Thus,
      children consider both personal and situational constraints on knowledge when
      evaluating the informativeness of causal interventions.

PMID- 18039544
TI  - Cerebral white matter deficiencies in pedophilic men.
AB  - The present investigation sought to identify which brain regions distinguish
      pedophilic from nonpedophilic men, using unbiased, automated analyses of the
      whole brain. T1-weighted magnetic resonance images (MRIs) were acquired from men
      who demonstrated illegal or clinically significant sexual behaviors or interests
      (n = 65) and from men who had histories of nonsexual offenses but no sexual
      offenses (n = 62). Sexual interest in children was assessed by participants'
      admissions of pedophilic interest, histories of committing sexual offenses
      against children, and psychophysiological responses in the laboratory to erotic
      stimuli depicting children or adults. Automated parcellation of the MRIs revealed
      significant negative associations between pedophilia and white matter volumes of
      the temporal and parietal lobes bilaterally. Voxel-based morphometry corroborated
      the associations and indicated that the regions of lower white matter volumes
      followed, and were limited to, two major fiber bundles: the superior fronto
      occipital fasciculus and the right arcuate fasciculus. No significant differences
      were found in grey matter or in cerebrospinal fluid (CSF). Because the superior
      fronto-occipital and arcuate fasciculi connect the cortical regions that respond
      to sexual cues, these results suggest (1) that those cortical regions operate as
      a network for recognizing sexually relevant stimuli and (2) that pedophilia
      results from a partial disconnection within that network.

PMID- 18039545
TI  - Triterpene saponins from Silphium radula.
AB  - Nine triterpene saponins (1-9) were isolated from leaves and stems of Silphium
      radula Nutt. (Asteraceae). Their structures were determined by extensive 1D
      ((13)C, (1)H, DEPT, TOCSY) and 2D NMR (NOESY, HSQC, HMBC) and ESI-MS studies. The
      compounds were identified as 3beta,6beta,16beta-trihydroxyolean-12-en-23-al-3-O
      beta-glucopyranosyl-16-O-beta-glucopyranoside (1), urs-12-ene-3beta,6beta,16beta
      triol-3-O-beta-galactopyranosyl-(1-->2)-beta-glucopyranoside (2),
      3beta,6beta,16beta-trihydroxyolean-12-en-23-oic acid-3-O-beta-glucopyranosyl-16-O
      beta-glucopyranoside (3), urs-12-ene-3beta,6beta,16beta,21beta-tetraol-3-O-beta
      glucopyranoside (4), olean-12-ene-3beta,6beta,16beta,21beta-tetraol-3-O-beta
      glucopyranoside (5), olean-12-ene-3beta,6beta,16beta,21beta,23-pentaol-3-O-beta
      glucopyranosyl-16-O-beta-glucopyranoside (6), olean-12-ene-3beta,6beta,16beta
      triol-3-O-beta-glucopyranosyl-16-O-alpha-arabinopyranosyl-(1-->2)-beta
      glucopyranoside (7), olean-12-ene-3beta,6beta,16beta,23-tetraol-3-O-beta
      glucopyranosyl-16-O-alpha-arabinopyranosyl-(1-->2)-beta-glucopyranoside (8),
      3beta,6beta,16beta,21beta-tetrahydroxyolean-12-en-23-al-3-O-beta-glucopyranoside
      (9). The presence of a 6beta-hydroxyl function was not common in the oleanene or
      ursene class and the aglycones of these compounds were not found previously in
      the literature. Moreover, the cytotoxic activities of the isolated compounds were
      tested against human breast cancer cell line MDA-MB-231. Results showed that
      compound 2 decreased cell proliferation in a statistically significant manner at
      25 microg/ml.

PMID- 18039546
TI  - Phytoalexins and polar metabolites from the oilseeds canola and rapeseed:
      differential metabolic responses to the biotroph Albugo candida and to abiotic
      stress.
AB  - The metabolites produced in leaves of the oilseeds canola and rapeseed (Brassica
      rapa L.) inoculated with either different races of the biotroph Albugo candida or
      sprayed with CuCl(2) were determined. This investigation established consistent
      phytoalexin (spirobrassinin, cyclobrassinin, and rutalexin) and phytoanticipin
      (indolyl-3-acetonitrile, arvelexin, caulilexin C, and 4-methoxyglucobrassicin)
      production in canola and rapeseed in response to both biotic and abiotic
      elicitation. In addition, a wide number of polar metabolites were isolated from
      infected leaves, including six new phenylpropanoids and two new flavonoids. The
      extractable chemical components of zoosporangia of A. candida and the anti
      oomycete activity of phytoalexins were determined as well. Overall, the results
      suggest that during the initial stage of the interaction, leaves of B. rapa have
      a similar response to virulent and avirulent races of A. candida, with respect to
      the accumulation of chemical defenses. After this stage, despite the higher
      phytoalexin concentration, the "compatible" races could overcome the plant
      defense system for further infection, but growth of the "incompatible" races was
      inhibited. Since results of bioassays showed that cyclobrassinin and brassilexin
      were more inhibitory to A. candida than rutalexin, the apparent redirection of
      the phytoalexin pathway towards rutalexin, avoiding cyclobrassinin and
      brassilexin accumulation might be caused by the pathogen. Alternatively, A.
      candida might be able to detoxify both cyclobrassinin and brassilexin, similar to
      necrotrophic plant pathogens. Overall, the correlation between phytoalexin
      production in infected or stressed leaves and the outcome of the plant-pathogen
      interaction suggested that A. candida was able to elude the plant defense
      mechanisms by, for example, redirecting the phytoalexin biosynthetic pathway.

PMID- 18039547
TI  - The unique properties of human NK cells in the uterine mucosa.
AB  - Natural killer (NK) cells are lymphocytes of the innate immune system that are
      able to kill hazardous pathogens and tumours. It was recently recognized that NK
      cells also possess non-destructive functions. NK cells were shown to interact
      with T, B, DC cells and macrophages and consequently shape the adaptive immune
      response. In addition, activated NK cells were shown to be quite efficient
      antigen-presenting cells. Here we review the unique properties of human NK cells
      in the uterine mucosa prior to and during pregnancy. We discuss the role of
      decidual NK cells and suggest that their major function is to assist in fetal
      development. Further we discuss the function and origin of endometrial NK cells
      and define some questions that need to be addressed in future research.

PMID- 18039548
TI  - An analysis of the relation between physical characteristics of prostate I-125
      seed implants and lower urinary tract symptoms: bladder hotspot dose and prostate
      size are significant predictors.
AB  - PURPOSE: Lower urinary tract symptoms are frequently observed after I-125 seed
      implantation of the prostate. More knowledge about causes and predictors is
      necessary to be able to develop less toxic implantation techniques. The aim of
      this study was to identify implantation related factors that contribute to post
      implant urinary morbidity. MATERIALS AND METHODS: Analysed was a group of 72
      patients that filled in a symptom score questionnaire before, 3 months and 6
      months after implantation as well as a group of 15 patients that suffered from
      acute urinary retention. Several dose-volume parameters of prostate, urethra and
      bladder wall were determined based on a post-implant TRUS-CT scan. RESULTS: The
      dose to a 1cm(3) hotspot in the bladder wall (D1cc-bl) as well as the prostate
      volume were independently correlated with urinary morbidity symptom scores at 3
      months (p=0.006 and p=0.005, respectively) and at 6 months (p=0.001 and p=0.015,
      respectively) after implantation. The number of implanted seeds and the D1cc-bl
      were significant discriminators (p<0.001 and p=0.015, respectively) for either
      mild or severe early urinary morbidity. CONCLUSION: Bladder hotspot dose appears
      to be an important dosimetric predictor for urinary morbidity both at 3 months
      and at 6 months after implantation. Other predictors are prostate volume, or
      equivalently, the number of implanted seeds.

PMID- 18039549
TI  - Respiratory gated beam delivery cannot facilitate margin reduction, unless
      combined with respiratory correlated image guidance.
AB  - PURPOSE/OBJECTIVE: In radiotherapy of targets moving with respiration, beam
      gating is offered as a means of reducing the target motion. The purpose of this
      study is to evaluate the safe magnitude of margin reduction for respiratory gated
      beam delivery. MATERIALS/METHODS: The study is based on data for 17 lung cancer
      patients in separate protocols at Rigshospitalet and Stanford Cancer Center.
      Respiratory curves for external optical markers and implanted fiducials were
      collected using equipment based on the RPM system (Varian Medical Systems). A
      total of 861 respiratory curves represented external measurements over 30
      fraction treatment courses for 10 patients, and synchronous external/internal
      measurements in single sessions for seven patients. Variations in respiratory
      amplitude (simulated coaching) and external/internal phase shifts were simulated
      by perturbation with realistic values. Variations were described by medians and
      standard deviations (SDs) of position distributions of the markers. Gating
      windows (35% duty cycle) were retrospectively applied to the respiratory data for
      each session, mimicking the use of commercially available gating systems. Medians
      and SDs of gated data were compared to those of ungated data, to assess potential
      margin reductions. RESULTS: External respiratory data collected over entire
      treatment courses showed SDs from 1.6 to 8.1mm, the major part arising from
      baseline variations. The gated data had SDs from 1.5 to 7.7mm, with a mean
      reduction of 0.3mm (6%). Gated distributions were more skewed than ungated, and
      in a few cases a marginal miss of gated respiration would be found even if no
      margin reduction was applied. Regularization of breathing amplitude to simulate
      coaching did not alter these results significantly. Simulation of varying phase
      shifts between internal and external respiratory signals showed that the SDs of
      gated distributions were the same as for the ungated or smaller, but the median
      values were markedly shifted. The gated distributions could generally not be
      covered by margins derived from ungated data, if the phase shift was not
      accounted for. CONCLUSIONS: Margins can only be reduced for respiratory gated
      radiotherapy, if respiratory baseline shifts and variations in external/internal
      motion correlation are accounted for. Gated beam delivery alone cannot facilitate
      margin reduction. In the worst case, margins must be increased to accommodate
      inter-fraction variations in respiration.

PMID- 18039550
TI  - Teaching on the spiritual dimension in care: the perceived impact on
      undergraduate nursing students.
AB  - The aim of the study unit, delivered in 2004-2005, to a cohort group of nursing
      students (n=65), who undertook the Diploma in Health Science, was to increase
      students' awareness about the spiritual dimension in nursing care so as to enable
      them to implement holistic care. The aim of this paper is to reveal the perceived
      impact of the study unit on students' life. This was derived from a written self
      reflection account, which was submitted on voluntary basis, additional to the
      written assignment. The majority of students (97%, n=63) performed this written
      exercise which seems to demonstrate the students' interest in this study unit.
      Excerpts from students' written personal reflection indicate the personal,
      academic and professional impact of the study unit on nursing students. The
      positive feedback from students sheds light on the importance of teaching
      undergraduate students on the spiritual dimension in care. This implies that such
      a study unit is to be integrated within the curriculum of nursing education for
      the benefit of the nurses themselves and to enable delivery of holistic care.

PMID- 18039551
TI  - Advances in the allogeneic transplantation for thalassemia.
AB  - Hematopoietic stem cell transplantation (HSCT) remains the only curative option
      for patients with thalassemia. Current results of transplantation in patients
      aged less than 17 years from matched related donors offer 80% to 87% probability
      of cure according to risk classes. Adult thalassemics treated with myeloablative
      conditioning continue to have inferior results because of their advanced stage of
      disease. With the introduction of high-resolution tissue typing techniques
      transplant centres worldwide are able to offer allogeneic HSCT to a much larger
      cohort of patients who could not benefit from transplantation because of lack of
      matched family donor. Although limited number of patients treated, results of
      transplant from unrelated matched donors are comparable to those obtained using
      sibling donors. Graft failure or rejection remains a significant cause of
      transplant failure in patients with thalassemia making difficult to perform
      reduced intensity conditioning regimens. Mixed chimerism is a common phenomenon
      after transplantation and is a risk factor for rejection. Ex-thalassemics still
      carry the clinical complications acquired during years of transfusion and
      chelation therapy. Longer follow-up and management of these complications in ex
      thalassemics are essential.

PMID- 18039552
TI  - Snapping turtles (Chelydra serpentina) as bioindicators in Canadian areas of
      concern in the Great Lakes Basin. II. Changes in hatching success and hatchling
      deformities in relation to persistent organic pollutants.
AB  - Hatching success and deformities in snapping turtle hatchlings (Chelydra
      serpentina) were evaluated using eggs collected from 14 sites in the Canadian
      lower Great Lakes, including Areas of Concern (AOC), between 2001 and 2004. Eggs
      were analyzed for PCBs, PBDEs, and pesticides. Between 2002 and 2004, hatchling
      deformity rates were highest in two AOCs (18.3-28.3%) compared to the reference
      sites (5.3-11.3%). Hatching success was poorest in three AOCs (71.3-73.1%)
      compared to the reference sites (86.0-92.7%). Hatching success and deformity
      rates were generally poorer in 2001 compared to 2002-2004, irrespective of the
      study location and could be due to egg handling stress in 2001. Hatching success
      and deformities were generally worst from the Wheatley Harbour, St. Lawrence
      River (Cornwall), Detroit River, and Hamilton Harbour AOCs. Associations between
      contaminant burdens with embryonic development were sufficiently poor that the
      biological relevance is questionable. Stressors not measured may have contributed
      to development abnormalities.

PMID- 18039553
TI  - Toxic effects of arsenic on Sinorhizobium-Medicago sativa symbiotic interaction.
AB  - Recently, the Rhizobium-legume symbiotic interaction has been proposed as an
      interesting tool in bioremediation. However, little is known about the effect of
      most common contaminants on this process. The phytotoxic effects of arsenic on
      nodulation of Medicago sativa have been examined in vitro using the highly
      arsenic resistant and symbiotically effective Sinorhizobium sp. strain MA11. The
      bacteria were able to grow on plates containing As concentrations as high as 10
      mM. Nevertheless, as little as 25-35 microM arsenite produced a 75% decrease in
      the total number of nodules, due to a 90% reduction in the number of rhizobial
      infections, as could be determined using the strain MA11 carrying a lacZ reporter
      gene. This effect was associated to root hair damage and a shorter infective root
      zone. However, once nodulation was established nodule development seemed to
      continue normally, although earlier senescence could be observed in nodules of
      arsenic-grown plants.

PMID- 18039554
TI  - Subchronic toxicity and toxicokinetics of LZB, a new proton pump inhibitor, after
      13-week repeated oral administration in dogs.
AB  - The subchronic toxicity and toxicokinetics of a novel proton pump inhibitor,
      pymeprazole (LZB), were investigated in beagle dogs by daily oral administration
      for 13 consecutive weeks. Three test groups received doses of 30, 100 and 300
      mg/kg/day of LZB. Rabeprazole of 60 mg/kg/day was used as positive control. The
      13-week repeated oral doses of LZB resulted in objective signs of mild
      gastrointestinal disturbance for high-dose group animals. One individual dog of
      high-dose group was found to be lethargy and astasia at the last month of
      administration; for hematology, mild anemia was observed at high-dose females;
      for clinical chemistry, higher cholest, trigly and gastrin were observed at high
      dose females, higher ASAT, ALAT, cholesterol, triglyceride and gastrin at high
      dose males were also observed; for histopathology, the primary effects of LZB
      were related to gastric mucosa of high-dose group seen by H and E or Grimelius
      stain. Impairment of surface epithelium was observed by SEM. The treat-related
      effects basically were reversible for a 4-week drug-free period. As for positive
      control group, 13-week oral administration of rabeprazole resulted in more severe
      toxicity than high-dose group of LZB although much lower dose was employed. The
      accumulation of LZB after 13-week oral administration was not notable at the
      toxic dose of 300 mg/kg/day. The toxic dose was considered to be 100mg/kg/day and
      the no-observed-adverse-effect level (NOAEL) to be 30 mg/kg/day, which is much
      higher than other PPIs. The toxicological target could be stomach, liver,
      hematological system and nervous system.

PMID- 18039555
TI  - Re: (-)-Hinokinin causes antigenotoxicity but not genotoxicity in peripheral
      blood of Wistar rats.

PMID- 18039556
TI  - Expression and function of the P2X(7) receptor in rat C6 glioma cells.
AB  - Our results demonstrate the first findings of expression and function of the
      purinergic P2X7 receptor (P2X7R) in rat C6 glioma cells. P2X7R mRNA and protein
      were present in unstimulated C6 cells and were up-regulated by cell exposure to
      the P2X7R agonist, 2',3'-(benzoyl-4-benzoyl)-ATP (BzATP). Activation of P2X7R in
      C6 in response to BzATP led to increased mobilization of intracellular calcium
      [Ca2+]i and formation of large pores. Chronic exposure of C6 cells to BzATP
      enhanced the expression of pro-inflammatory factors including MCP-1, IL-8 and
      VEGF. In a scratch-wound migration assay, the P2X7R was shown to regulate cell
      mobility. The overall results suggest that P2X7R activation in C6 is linked with
      increased pro-inflammatory factors and tumor cell migration.

PMID- 18039557
TI  - Amifostine increases cure rate of cisplatin on ascites hepatoma 22 via
      selectively protecting renal thioredoxin reductase.
AB  - It has been demonstrated via in vitro experiments that the anti-cancer drug
      cisplatin (CDDP) can inactivate thioredoxin reductase (TrxR), a molecular target
      for cancer therapy. The present study in mice revealed that CDDP at
      pharmacological doses inhibited TrxR activity in both ascitic hepatoma 22 (H22)
      cells and kidney, leading to suppression of H22 cells proliferation along with
      nephrotoxicity. Amifostine, a clinical used cytoprotective agent, protected
      against CDDP-induced TrxR inactivation in kidney but not in H22 cells. Such an
      excellent selective modulation of amifostine on TrxR led us to exploit the
      potential of amifostine in increasing cure rate of CDDP on cancer. In mice, CDDP
      at the doses of 5 and 7.5 mg/kg once weekly for 4 weeks could not completely
      control H22 ascites development and the cure rate was no more than 12.5%; CDDP 9
      mg/kg by the same schedule prominently suppressed the ascites development, but
      finally resulted in 87.5% mortality caused by CDDP toxicity. Thus, these dose
      dependent therapeutic results well recapitulated the clinical dilemma of
      chemotherapy on cancer. However, co-treatment of CDDP (9 mg/kg) and amifostine
      largely reduced CDDP toxicity, and obtained a cure rate as high as 87.5%.
      Overall, the present study demonstrates both pharmacological and toxicological
      effects of CDDP involve TrxR inactivation, and the large enhancement on CDDP cure
      rate in H22 ascites model by using amifostine is, at least in part, ascribed to
      its selective modulation on TrxR.

PMID- 18039558
TI  - Immunization with a recombinant GnRH vaccine conjugated to heat shock protein 65
      inhibits tumor growth in orthotopic prostate cancer mouse model.
AB  - We have previously shown that anti-GnRH antibodies responses can be induced by
      synthetic GnRH3-hinge-MVP peptide. In this study, GnRH3-hinge-MVP of conjugation
      to heat shock protein 65 was used as an adjuvant-free vaccine to assess the
      therapeutic effects of GnRH immunoneutralisation on tumor development in the mice
      model. Compared with mice treated with Hsp65 and PBS, mice of the o.t. model
      receiving in situ treatment GnRH3-hinge-MVP-Hsp65 had significant prolongation of
      survival and suppression of local tumor growth. Serum levels of both testosterone
      and luteinizing hormone were reduced by treatment with GnRH3-hinge-MVP-Hsp65
      (p<0.05). Further analyses of cell mediated immune responses showed that GnRH3
      hinge-MVP-Hsp65 induced stronger lymphocyte proliferative responses and higher
      levels of IFN-gamma (p<0.001). The conjugation of the recombinant GnRH peptide to
      Hsp65 could be considered a promising approach for the development of an
      efficacious vaccine against the prostate cancer.

PMID- 18039559
TI  - Health-related quality of life as a valid outcome in the treatment of advanced
      colorectal cancer.
AB  - With the recent trend of improved survival, there has been a marked interest in
      reviewing and refining the contribution of health related quality of life (HRQoL)
      outcome measures of treatment in advanced colorectal cancer. However, if HRQoL
      data are going to be of clinical value and help both physicians and patients make
      decisions there is a need for a consensus on both the design and methods of
      measurement of HRQoL in clinical trials, and an acknowledgement of the
      interpretation of the outcomes in clinical practice. Whilst it is encouraging to
      find that the quality of HRQoL measurement in clinical research has improved
      significantly over the last fifteen years, with a growing number of trial-based
      HRQoL studies, there is still the potential to improve the use of HRQoL in
      clinical decision making in advanced colorectal cancer. There is also the need to
      further refine measurement of HRQoL to provide useful data specific to these
      patients. It is anticipated that developments such as the liver metastases module
      EORTC (QLQ-LMC21) questionnaire will increase the sensitivity to change of the
      generic cancer measure, the EORTC QLQ-C30 and will provide essential HRQoL
      information regarding the use of treatments in both the curative and palliative
      settings. Furthermore, easy to use simple tools such as the "minimum standard
      checklist for evaluating HRQoL outcomes in cancer clinical trials" might be of
      help in guiding investigators on the basis of minimum criteria.

PMID- 18039560
TI  - Location of involved mesorectal and extramesorectal lymph nodes in patients with
      primary rectal cancer: preoperative assessment with MR imaging.
AB  - AIM: The purpose of this study is to evaluate the location of involved mesorectal
      and extramesorectal lymph nodes as depicted on preoperative MRI. Preoperative
      availability of this information might be useful for the surgeon as well as the
      radiation therapist and medical oncologist for optimal treatment strategy: type
      and extent of neoadjuvant treatment as well as extent of surgical resection.
      METHODS: Forty-one patients with biopsy-proven rectal cancer were included. All
      patients underwent preoperative MRI using USPIO (lymph node specific contrast
      agent). Location of all mesorectal and extramesorectal nodes visible on MRI was
      recorded, as well as USPIO prediction on nodal status. Lesion-by-lesion analysis
      using histology after surgery was performed for patients who did not receive long
      course chemoradiation therapy. RESULTS: There were 438 nodes visible, 94 of which
      were malignant. Most nodes are located in the laterodorsal part of the
      mesorectum, with no difference in distribution between positive and negative
      nodes. In relation to height of tumor, the majority of positive nodes are located
      at tumor height or above. There were significantly more negative nodes (9.6%)
      located below tumor height as compared to positive nodes (2.1%). There were 40
      extramesorectal nodes, in 16 patients, 5 of which were positive in 4 patients.
      All patients had distal rectal cancer. CONCLUSION: In conclusion, positive
      mesorectal nodes are located in the laterodorsal part of the mesorectum, at tumor
      height or above. Positive nodes distal to the tumor are rare, and occur in
      patients with more proximal nodal metastases. Positive extramesorectal nodes
      mainly occur in patients with distal rectal cancer with nodal metastases in the
      mesorectum.

PMID- 18039561
TI  - Genome-wide analysis of chlamydiae for promoters that phylogenetically footprint.
AB  - Currently, there is a lack of phylogenetic footprinting programmes that can take
      advantage of multiple whole genome sequences of different species within the same
      bacterial genus. Therefore, we have developed and tested a position weight matrix
      based programme called Footy, that performs genome-wide analysis of bacterial
      genomes for promoters that phylogenetically footprint. When Footy was used to
      analyse the non-coding regions upstream of genes from three chlamyidal species
      for promoters that phylogenetically footprint, it predicted a total of 42
      promoters, of which 41 were new. Ten of the 41 new promoters predicted by Footy
      were biologically assayed in Chlamydia trachomatis by mapping the 5' end of the
      transcripts for the associated genes. The primer extension assay validated seven
      of the 10 promoters. When Footy was compared to two other accepted methods for
      genome-wide prediction of promoters in bacteria (the standard PWM method and
      MITRA), Footy performed equally as well or better than these programmes. This
      paper, therefore, shows the value of a bioinformatics programme able to perform
      genome-wide analysis of bacteria for promoters that phylogenetically footprint.

PMID- 18039562
TI  - Enhanced nasal absorption of hydrophilic markers after dosing with AT1002, a
      tight junction modulator.
AB  - AT1002 is a six-mer synthetic peptide, H-FCIGRL-OH, that retains the delta G and
      Zot biological activity of reversibly opening tight junctions and increases the
      paracellular transport of drugs. The objective of this study was to evaluate the
      possible use of AT1002 in enhancing the nasal availability of macromolecules
      using large paracellular markers as model agents. Male Sprague-Dawley rats
      cannulated in the jugular vein were randomly assigned to receive radiolabelled
      paracellular markers, [14C]PEG4000 or [14C]inulin, with/without AT1002, for each
      intranasal study. The plasma concentration of PEG4000 with AT1002 (10mg/kg) was
      significantly higher than that from PEG4000 control over 360 min following
      intranasal administration. The AUC0-360 min and Cmax from the PEG4000/AT1002
      (10mg/kg) treatment were statistically (p<0.05) increased to 235% and 357%, of
      control, respectively. When inulin was administered with AT1002 (10 mg/kg), the
      plasma concentration was significantly higher (p<0.05) than control over 360 min,
      and increases (p<0.05) of 292% and 315% for AUC0-360 min and Cmax over control
      were observed, respectively. AT1002 significantly increased the nasal absorption
      of molecular weight markers, PEG4000 and inulin. This study suggests that AT1002
      may be used to enhance the systemic availability of macromolecules when
      administered concurrently.

PMID- 18039564
TI  - Expression levels of p53 and p73 isoforms in stage I and stage III ovarian
      cancer.
AB  - The p53 gene has been investigated for its role in epithelial ovarian cancer but
      data collected until now are contradictory. The evidence that p53 belongs with
      p63 and p73 to a family of transcription factors re-opened interest in this gene
      family. Here, we used quantitative real time RT-PCR to determine expression
      levels of TAp53, TAp73 and their N-terminal splice variants in a cohort of 169
      ovarian cancer patients with stage I and stage III disease. The TAp73 levels in
      stage III biopsies differed by 100-fold depending on the p53 status and overall
      survival appears to be significantly related to DeltaNp73 expression. Kaplan
      Meyer analyses did not suggest a correlation between overall survival and levels
      of TAp73, DeltaNp73 or the DeltaNp73/TAp73 ratio. In conclusion, these data
      suggest that at least in our patient cohort p53 and p73 expression levels are not
      correlated to malignant progression of ovarian cancer. They might, however, play
      a role in tumour initiation.

PMID- 18039565
TI  - The actual citation impact of European oncological research.
AB  - This study provides an overview of the research performance of major European
      countries in the field Oncology, the most important journals in which they
      published their research articles, and the most important academic institutions
      publishing them. The analysis was based on Thomson Scientific's Web of Science
      (WoS) and calculated bibliometric indicators of publication activity and actual
      citation impact. Studying the time period 2000-2006, it gives an update of
      earlier studies, but at the same time it expands their methodologies, using a
      broader definition of the field, calculating indicators of actual citation
      impact, and analysing new and policy relevant aspects. Findings suggest that the
      emergence of Asian countries in the field Oncology has displaced European
      articles more strongly than articles from the USA; that oncologists who have
      published their articles in important, more general journals or in journals
      covering other specialties, rather than in their own specialist journals, have
      generated a relatively high actual citation impact; and that universities from
      Germany, and--to a lesser extent--those from Italy, the Netherlands, UK, and
      Sweden, dominate a ranking of European universities based on number of articles
      in oncology. The outcomes illustrate that different bibliometric methodologies
      may lead to different outcomes, and that outcomes should be interpreted with
      care.

PMID- 18039567
TI  - Semi-mechanistic modelling of the tumour growth inhibitory effects of LY2157299,
      a new type I receptor TGF-beta kinase antagonist, in mice.
AB  - Human xenografts Calu6 (non-small cell lung cancer) and MX1 (breast cancer) were
      implanted subcutaneously in nude mice and LY2157299, a new type I receptor TGF
      beta kinase antagonist, was administered orally. Plasma levels of LY2157299,
      percentage of phosphorylated Smad2,3 (pSmad) in tumour, and tumour size were used
      to establish a semi-mechanistic pharmacokinetic/pharmacodynamic model. An
      indirect response model was used to relate plasma concentrations with pSmad. The
      model predicts complete inhibition of pSmad and rapid turnover rates [t(1/2)
      (min)=18.6 (Calu6) and 32.0 (MX1)]. Tumour growth inhibition was linked to pSmad
      using two signal transduction compartments characterised by a mean signal
      propagation time with estimated values of 6.17 and 28.7 days for Calu6 and MX1,
      respectively. The model provides a tool to generate experimental hypothesis to
      gain insights into the mechanisms of signal transduction associated to the TGF
      beta membrane receptor type I.

PMID- 18039566
TI  - The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in
      patients with advanced breast cancer: results of a phase I study with
      pharmacokinetics.
AB  - PURPOSE: To investigate the safety and pharmacokinetics (PK) of combined
      treatment with letrozole and the oral mTOR inhibitor RAD001 in patients with
      metastatic breast cancer stable or progressing after > or = 4 months on letrozole
      alone. METHODS: Eighteen patients received letrozole (2.5 mg/day) and RAD001 at 5
      mg/day (cohort 1) or 10 mg/day (cohort 2). In the absence of DLT in cohort 1,
      cohort 2 was expanded to 12 patients to obtain additional safety and PK data.
      RESULTS: Most common adverse events were stomatitis (50.0% of patients), fatigue
      (44.4%), anorexia and/or decreased appetite (44.4%), diarrhoea (38.9%), headache
      (33.3%) and rash (33.3%). There was 1 DLT, a grade 3 thrombocytopaenia in cohort
      2. No clinically relevant PK interaction was detected. Seven patients received
      the combination therapy for >6 months. One patient had a complete response, and
      one had a 28% reduction in liver metastases, both in cohort 2. CONCLUSION: Daily
      therapy with RAD001 plus letrozole is promising: the results suggest anti-tumour
      activity with no PK interactions. The overall safety profile of the combination
      is consistent with that expected for RAD001 monotherapy. A daily dose of RAD001
      10mg is recommended for further trials.

PMID- 18039568
TI  - Pulping cardoon (Cynara cardunculus) with peroxyformic acid (MILOX) in one single
      stage.
AB  - In this work, depithed cardoon stalk (Cynara cardunculus) has been used with the
      objective of obtaining bleachable pulps. The material, once properly prepared,
      was subjected to one-step peroxyformic acid delignification. In order to study
      the process, a face-centred second order factorial design was developed which
      allowed the determination of the influences of four variables: concentrations of
      formic acid and hydrogen peroxide in the cooking liquor and the time and
      temperature of the treatment. Empirical mathematical models have been obtained
      which predict the yield, kappa index, residual lignin content, and viscosity of
      the pulps. These models demonstrate that in general the delignification was
      extensive, producing pulps with kappa indexes less than 25 in the majority of
      cases, with good yields in the range of 45-60%. However, the pulps seem to have
      been degraded in the reaction media, as can be deduced from the low viscosity
      values found: 260-520 mL/g.

PMID- 18039569
TI  - Investigation of the biotransformation of pentachlorophenol and pulp paper mill
      effluent decolorisation by the bacterial strains in a mixed culture.
AB  - Mixed culture of two bacterial strains Bacillus sp. and Serratia marcescens
      showed potential pentachlorophenol (PCP) degradation and decolorisation of pulp
      paper mill effluent. The physico-chemical quality of pulp paper mill effluent has
      been analyzed after 168 h incubation period degraded by mixed culture. The study
      revealed that it has decreased high load of BOD, COD, TS, TDS, TSS, sulphate,
      phosphate, total nitrogen, total phenols, metals and different salts (i.e.
      chloride, sodium, nitrate, potassium) at 168 h incubation period. PCP degradation
      in pulp paper mill effluent was confirmed by HPLC analysis. Mixed culture was
      found to degrade PCP up to (94%) present in pulp paper mill effluent with 1%
      glucose and 0.5% peptone (w/v) at 30+/-1 degrees C, pH 8.0+/-0.2 at 120 rpm in
      168 h incubation period. The simultaneous release of chloride ion up to 1,200
      mg/l at 168 h emphasized the bacterial dechlorination in the medium. The pulp
      paper mill effluent degradation was also supported by decline in pH, AOX
      (absorbable organic halides), color, D.O., BOD, COD and PCP. The analysis of pulp
      paper mill effluent degradation products by GC-MS analysis revealed the formation
      of low molecular weight compound like 2-chlorophenol (RT=3.8 min) and
      tetrachlorohydroquinone (RT=11.86 min) from PCP extracted degraded sample.
      Further, mixed culture may be used for bioremediation of PCP containing pulp
      paper mill waste in the environment.

PMID- 18039570
TI  - Design, synthesis and antimalarial activity of benzene and isoquinoline
      sulfonamide derivatives.
AB  - A new series of benzene and isoquinoline sulfonamide derivatives were synthesized
      by nucleophilic displacement reaction on benzene and isoquinoline sulfonyl
      chlorides by substituted amines (primary and secondary). The title compounds were
      evaluated for antimalarial activity against Plasmodium falciparum in vitro and
      showed MIC in the range of 2-50 microg/mL.

PMID- 18039571
TI  - Calcitonin gene-related peptide (CGRP) receptor antagonists: investigations of a
      pyridinone template.
AB  - In our effort to find potent, orally bioavailable CGRP receptor antagonists for
      the treatment of migraine, a novel series based on a pyridinone template was
      investigated. After optimizing the privileged structure and the placement of the
      attached phenyl ring, systematic SAR was carried out on both the N-alkyl and C-5
      aryl substituents. Several analogs with good potency and pharmacokinetic profiles
      were identified.

PMID- 18039572
TI  - Design, synthesis, and biological activity of piperidine diamine derivatives as
      factor Xa inhibitor.
AB  - Previously, we identified cyclohexane diamine derivative 1 as orally bioavailable
      factor Xa inhibitor. We have investigated two racemic cis-piperidine diamine
      derivatives 2 and 3 based on 1. Compounds 2a-e showed higher fXa inhibitory
      activity, anticoagulant activity, and aqueous solubility than 3a-e having same
      substituent. Compounds 2a, 2c, 2e, and 2g-m having sp2 nitrogen, especially amide
      and urea derivatives, showed potent anticoagulant activity. Compounds 2h and 2k
      showed high oral activities in rats.

PMID- 18039573
TI  - Antitumor effects of curcumin and structurally beta-diketone modified analogs on
      multidrug resistant cancer cells.
AB  - Using concepts of bioisostery a series of curcumin analogs were synthesized: the
      diketonic system of the compound was elaborated into enaminones, oximes, and the
      isoxazole heterocycle. The cell growth inhibitory and apoptosis inducing effects
      of the new analogs were evaluated by in vitro assays in the hepatocellular
      carcinoma HA22T/VGH cells, as well as in the MCF-7 breast cancer cell line and in
      its multidrug resistant (MDR) variant MCF-7R. Increased antitumor activity on all
      cell lines was found with the isoxazole analog and especially with the benzyl
      oxime derivative; in the HA22T/VGH cell model, the latter compound inhibited
      constitutive NF-kappaB activation.

PMID- 18039574
TI  - Synthesis and analysis of stabilizing ligands for FKBP-derived destabilizing
      domains.
AB  - We recently identified mutants of the human FKBP12 protein that are unstable and
      rapidly degraded when expressed in mammalian cells. We call these FKBP mutants
      destabilizing domains (DDs), because their instability is conferred to any
      protein fused to the DDs. A cell-permeable ligand binds tightly to the DDs and
      prevents their degradation, thus providing small molecule control over
      intracellular protein levels. We now report the synthesis and functional
      characterization of a stabilizing ligand called Shield-2. The synthesis of Shield
      2 is efficient, and this ligand binds to the FKBP(F36V) protein with a
      dissociation constant of 29 nM.

PMID- 18039575
TI  - Synthesis and evaluation of a gamma-lactam as a highly selective EP2 and EP4
      receptor agonist.
AB  - Gamma-lactam analogs (2) of EP(4) receptor agonists were identified by
      substitution of the pyrazolidinone ring (1) with a pyrrolidinone ring. Several
      compounds (such as 2a, 2h) with high potency, selectivity and acceptable PK
      profiles were discovered. These were assessed in animal models of ovulation
      induction and bronchoconstriction.

PMID- 18039576
TI  - Efficient enhancement of DNA cleavage activity by introducing guanidinium groups
      into diiron(III) complex.
AB  - Inspired by the structures of natural nucleases, guanidinium groups were
      introduced into binuclear iron(III) systems. Compared with the corresponding
      analogue without guanidinium groups, the new diiron(III) system led to
      considerable rate enhancement on DNA cleavage. The cooperativity between metal
      ions and guanidine groups was evidenced by the fact that no significant cleavage
      was observed after incubating pBR322 plasmid DNA with non-metalated ligands or
      free Fe3+ ion. DNA binding experiments indicated that introduction of positively
      charged guanidinium groups can obtain more than one order of magnitude
      enhancement in the affinity of complex with DNA.

PMID- 18039578
TI  - 2-Aminoresorcinol is a potent alpha-glucosidase inhibitor.
AB  - A series of aminoresorcinols and related compounds were tested for rat intestinal
      alpha-glucosidase inhibition and these results suggested that the 2
      aminoresorcinol moiety of 6-amino-5,7-dihydroxyflavone (2) is important to exert
      the intestinal alpha-glucosidase inhibitory activity and 2-aminoresorcinol (4),
      itself, is a potent alpha-glucosidase inhibitor and inhibited sucrose-hydrolyzing
      activity of rat intestinal alpha-glucosidase uncompetitively.

PMID- 18039577
TI  - Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38alpha MAP
      kinase inhibitors with excellent in vivo antiinflammatory properties.
AB  - Herein we report investigations into the p38alpha MAP kinase activity of
      trisubstituted imidazoles that led to the identification of compounds possessing
      highly potent in vivo activity. The SAR of a novel series of imidazopyridines is
      demonstrated as well, resulting in compounds possessing cellular potency and
      enhanced in vivo activity in the rat collagen-induced arthritis model of chronic
      inflammation.

PMID- 18039579
TI  - Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile
      group.
AB  - A series of (4beta-substituted)-L-prolylpyrrolidine analogs lacking the
      electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV
      (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated.
      Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine analog
      8, which was found by high-speed analog synthesis, was carried out to improve the
      potency and duration of action. A representative compound 26 was evaluated to
      assess its effect on the plasma glucose level after the oGTT (oral glucose
      tolerance test) in normal rats. Structure-activity relationships (SAR) are also
      presented.

PMID- 18039580
TI  - IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis?
AB  - Interleukin-17A (IL-17A) contributes to the pathogenesis of arthritis. Data from
      experimental arthritis indicate IL-17 receptor signaling as a critical pathway in
      turning an acute synovitis into a chronic destructive arthritis. The
      identification of six IL-17 family members (IL-17A-F) may extend the role of this
      novel cytokine family in the pathogenesis of chronic destructive joint
      inflammation. Whether the successful anti-IL-17A cytokine therapy in murine
      arthritis can be effectively translated to human arthritis need to be tested in
      clinical trials in humans. Interestingly, IL-17A and IL-17F are secreted by the
      novel T helper subset named Th17. This novel pathogenic T cell population induces
      autoimmune inflammation in mice and is far more efficient at inducing Th1
      mediated autoimmune inflammation in mice than classical Th1 cells (IFN-gamma). In
      addition to IL-17A and IL-17F, Th17 cells are characterized by expression of IL
      6, TNF, GM-CSF, IL-21, IL-22 and IL-26. Th17 cells have been established as a
      separate lineage of T helper cells in mice distinct from conventional Th1 and Th2
      cells. Whether this also applies to human Th17 and whether RA is a Th1 or a Th17
      mediated disease is still not clear. This review summarizes the findings about
      the role of IL-17 in arthritis and discusses the impact of the discovery of the
      novel Th17 cells for arthritis. Further studies are needed to unravel the role of
      Th17 cells and the interplay of IL-17 and other Th17 cytokines in the
      pathogenesis of arthritis and whether regulating Th17 cell activity will have
      additional value compared to neutralizing IL-17A activity alone. This might help
      to reach the ultimate goal not only to treat RA patients but to prevent the
      development of this crippling disease.

PMID- 18039581
TI  - Expression, purification and fluorine-18 radiolabeling of recombinant S100
      proteins--potential probes for molecular imaging of receptor for advanced
      glycation endproducts (RAGE) in vivo.
AB  - Data concerning the pathophysiological role of the interaction of circulating
      S100 proteins, a multigenic family of Ca(2+)-modulated proteins, with the
      receptor for advanced glycation endproducts (RAGE) in cardiovascular diseases,
      inflammatory processes, and tumorigenesis in vivo are scarce. One reason is the
      shortage of suitable radiotracer methods. We report a novel methodology using
      recombinant human S100A1, S100B, and S100A12 as potential probes for molecular
      imaging of this interaction. Therefore, human S100 proteins were cloned as GST
      fusion proteins in the bacterial expression vector pGEX-6P-1 and expressed in E.
      coli strain BL21. Purified recombinant human S100 proteins were radiolabeled with
      the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4
      [(18)F]fluorobenzoate ([(18)F]SFB). The radiolabeled recombinant S100 proteins
      ((18)F-S100) were used in biodistribution experiments and small animal positron
      emission tomography (PET) studies in rats. The tissue-specific distribution of
      (18)F-S100 proteins in vivo correlated well with the anatomical localization of
      RAGE, e.g., in lungs and in the vascular system. These findings indicate
      circulating S100A1, S100B, and S100A12 proteins to be ligands for RAGE in rats in
      vivo. The approach allows the use of small animal PET and provides novel probes
      to delineate functional expression of RAGE under normal and pathophysiological
      conditions in rodent models of disease.

PMID- 18039582
TI  - Incorporating gaps as phylogenetic characters across eight DNA regions:
      ramifications for North American Psoraleeae (Leguminosae).
AB  - The impact of including insertion/deletion events as phylogenetic characters was
      explored within North American Psoraleeae (Leguminosae). This comprehensive
      analysis of the impact of gap character incorporation spanned four different
      indel coding schemes, gaps coded as missing characters, simple binary characters,
      multi-state characters, and as a 5th state, across two optimality criteria:
      maximum parsimony and Bayesian Inference. Two nuclear (ITS and Waxy) and six
      chloroplast (trnS/G, trnL/F, trnK, matK, trnD/T, and rpoB-trnC) DNA regions were
      sequenced from 43 species of North American Psoraleeae as the foundation of the
      study. Our results suggest that gaps can provide a substantial percentage of
      informative characters and can increase phylogenetic resolution and nodal branch
      support. Phylogenetic signal within indels was higher in chloroplast regions
      relative to nuclear regions, demonstrating their inclusion as especially
      important in chloroplast-based phylogenetic studies. Phylogenetic analysis of
      generic relationships within Psoraleeae is largely congruent with that proposed
      by Grimes (1990) with a few exceptions. New World species are supported as a
      monophyletic group. Our analyses suggest that Otholobium may need to be split
      into two genera and that Psoralidium is polyphyletic and will require movement of
      Psoralidium tenuiflorum to Pediomelum.

PMID- 18039583
TI  - Evolutionary insights inferred by molecular analysis of the ITS1-5.8S-ITS2 and
      IGS Avena sp. sequences.
AB  - In an attempt to clarify phylogenetic and genome relationships among 35 diploid
      (A and C genomes), 13 tetraploid (AB and AC genomes) and 6 hexaploid (ACD genome)
      Avena taxa, 71 clones of the ITS1-5.8S-ITS2 fragment were sequenced, aligned and
      a network was constructed. In addition, the intergenic spacer (IGS) fragment was
      fingerprinted by means of a RFLP analysis using three different restriction
      enzymes. Both approaches led to comparable results. Clustering among the 54 Avena
      sp. entries was according to karyotype. Major genic divergence between the A and
      C genomes was revealed, while distinction among the A and B/D genomes was not
      possible. High affinity among the AB genome tetraploids and the A(s) genome
      diploid A. lusitanica was found, while AC genome tetraploids and ACD hexaploids
      were highly affiliated with the A(l) genome diploid A. longiglumis. The possible
      role of A. longiglumis in Avena sp. evolution is discussed.

PMID- 18039584
TI  - On the participation of mTOR in recognition memory.
AB  - Evidence indicates that activation of the neuronal protein synthesis machinery is
      required in areas of the brain relevant to memory for consolidation and
      persistence of the mnemonic trace. Here, we report that inhibition of hippocampal
      mTOR, a protein kinase involved in the initiation of mRNA translation,
      immediately or 180min but not 540min after training impairs consolidation of long
      term object recognition memory without affecting short-term memory retention or
      exploratory behavior. When infused into dorsal CA1 after long-term memory
      reactivation in the presence of familiar objects the mTOR inhibitor rapamycin
      (RAP) did not affect retention. However, when given immediately after exposing
      animals to a novel and a familiar object, RAP impaired memory for both of them.
      The amnesic effect of the post-retrieval administration of RAP was long-lasting,
      did not happen after exposure to two novel objects or following exploration of
      the training arena in the absence of other stimuli, suggesting that it was
      contingent with reactivation of the consolidated trace in the presence of a
      behaviorally relevant and novel cue. Our results indicate that mTOR activity is
      required in the dorsal hippocampus for consolidation of object recognition memory
      and suggest that inhibition of this kinase after memory retrieval in the presence
      of a particular set of cues hinders persistence of the original recognition
      memory trace.

PMID- 18039585
TI  - Hippocampal low-frequency stimulation and chronic mild stress similarly disrupt
      fear extinction memory in rats.
AB  - Disruptions of fear extinction-related potentiation of synaptic efficacy in the
      connection between the hippocampus (HPC) and the medial prefrontal cortex (mPFC)
      have been shown to impair the recall of extinction memory. This study was
      undertaken to examine if chronic mild stress (CMS), which is known to alter
      induction of HPC-mPFC long-term potentiation, would also interfere with both
      extinction-related HPC-mPFC potentiation and extinction memory. Following fear
      conditioning (5 tone-shock pairings), rats were submitted to fear extinction (20
      tone-alone presentations), which produced an increase in the amplitude of HPC
      mPFC field potentials. HPC low-frequency stimulation (LFS), applied immediately
      after training, suppressed these changes and induced fear return during the
      retention test (5 tone-alone presentations). CMS, delivered before fear
      conditioning, did not interfere with fear extinction but blocked the development
      of extinction-related potentiation in the HPC-mPFC pathway and impaired the
      recall of extinction. These findings suggest that HPC LFS may provoke metaplastic
      changes in HPC outputs that may mimic alterations associated with a history of
      chronic stress.

PMID- 18039586
TI  - A multi-locus phylogeny for Phytophthora utilizing markers derived from complete
      genome sequences.
AB  - Phytophthora species are devastating plant pathogens in both agricultural and
      natural environments. Due to their significant economic and environmental impact,
      there has been increasing interest in Phytophthora genetics and genomics,
      culminating in the recent release of three complete genome sequences (P. ramorum,
      P. sojae, and P. infestans). In this study, genome and other large sequence
      databases were used to identify over 225 potential genetic markers for
      phylogenetic analyses. Here, we present a genus-wide phylogeny for 82
      Phytophthora species using seven of the most informative loci (approximately 8700
      nucleotide sites). Our results support the division of the genus into 10 well
      supported clades. The relationships among these clades were rigorously evaluated
      using a number of phylogenetic methods. This is the most comprehensive study of
      Phytophthora relationships to date, and many newly discovered species have been
      included. A more resolved phylogeny of Phytophthora species will allow for better
      interpretations of the overall evolutionary history of the genus.

PMID- 18039587
TI  - The Agrocybe aegerita mitochondrial genome contains two inverted repeats of the
      nad4 gene arisen by duplication on both sides of a linear plasmid integration
      site.
AB  - The Agrocybe aegerita mitochondrial genome possesses two polB genes with linear
      plasmid origin. The cloning and sequencing of the regions flanking Aa-polB P1
      revealed two large inverted repeats (higher than 2421 nt) separated by a single
      copy region of 5834 nt. Both repeats contain identical copies of the nad4 gene.
      The single copy region contains two disrupted genes with plasmid origin Aa-polB
      P1 and a small ORF homologous to a small gene described in two basidiomycete
      linear plasmids. The phylogenetic analyses argue in favor of a same plasmid
      origin for both genes but, surprisingly, these genes were separated by a
      mitochondrial tRNA-Met. Both strands of the complete region containing the two
      nad4 inverted copies and the tRNA-Met appear to be transcribed on large
      polycistronic mRNAs. A model summarizing the events that would have occurred is
      proposed: (1) capture of the tRNA by the plasmid before its integration in the
      mtDNA or acquisition of the tRNA gene by recombination after the plasmid
      integration, (2) integration of the plasmid in the mtDNA, accompanied by a large
      duplication containing the nad4 gene and (3) erosion of the plasmid sequences by
      large deletions and mutations.

PMID- 18039588
TI  - Low frequency of the CYP21A2 deletion in ethnic Chinese (Taiwanese) patients with
      21-hydroxylase deficiency.
AB  - Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder
      which causes more than 90% of CAH cases due to defects in the steroid 21
      hydroxylase gene (CYP21A2). The frequency of large mutations was determined in
      200 ethnic Chinese (i.e., Taiwanese) CAH patients belonging to 200 families with
      different clinical forms of CYP21A2 deficiency over 10 years of molecular
      diagnoses. For a large-gene deletion (or conversion) and the CYP21A2 deletion
      identification, a PCR product covering the TNXB gene and the 5'-end of the
      CYP21A2 gene with TaqI endonuclease digestion was analyzed by electrophoresis on
      agarose gels. For CYP21A2 mutational analysis, secondary PCR amplification of the
      amplification-created restriction site method was applied. From the results of
      the analysis, we found that large-gene deletions (or conversions) occurred in
      7.5% of the alleles including three different types of the chimeric
      CYP21A1P/CYP21A2 genes and the haplotype of IVS2-12A/C>G in combination with the
      707-714del mutation (without the P30L mutation). The CYP21A2 deletion occurred in
      2.0% of the alleles which contained three types of the chimeric TNXA/TNXB genes
      with two novel ones. We concluded that the CYP21A2 deletion in the ethnic Chinese
      (Taiwanese) patients exhibits a low occurrence, with the haplotype of the IVS2
      12A/C>G in combination with the 707-714del mutation (without the P30L mutation)
      being prevalent among large gene deletions or conversions.

PMID- 18039589
TI  - Allele frequencies of 14 STR loci in the population of Malta.
AB  - Allele frequencies of 14 STR loci (D13S317, D16S539, D2S1338, vWA, TPOX, D18S51,
      D5S818, FGA, D8S1179, D21S11, D7S820, CSF1PO, TH01 and D3S1358) observed in the
      population of Malta are being reported. Polymerase chain reaction (PCR)
      amplification using the AmpFl STR Identifiler kit was performed in a random
      sample of 157 subjects (314 chromosomes). Markers D2S1338, D18S51 and FGA had the
      highest power of discrimination (PD) values while TPOX was the least informative
      marker. Allele frequencies observed in the Maltese population were also compared
      with those of other populations from the Mediterranean region, Europe and Africa.
      Our data is useful for anthropological and other comparative studies of
      populations and is powerful for forensic and paternity testing in the Maltese
      islands.

PMID- 18039590
TI  - Reliability of intensity dependence of auditory-evoked potentials.
AB  - OBJECTIVE: Intensity dependence of auditory-evoked potentials (IAEP) is a
      suggested indicator of serotonergic neurotransmission. In contrast to its
      clinical renaissance, the reliability of IAEP has only been examined in a few
      studies, most of which are limited due to the possibly confounding effects of age
      and gender. Therefore, the present study examines different reliabilities of
      various IAEP parameterizations while controlling for age and gender. METHODS:
      Auditory-evoked potentials were recorded from 166 students. Of these 37 women and
      25 men were retested after three weeks. RESULTS: Test-retest and odd-even
      reliabilities were remarkable at Cz in both females (r=.88/.86) and males
      (r=.82/.79). Reliabilities were higher in women, higher with linear than median
      slopes and best at Cz. Bisection of sweep number, split-half reliability, the
      second run, and lower intensities revealed lower reliabilities. CONCLUSIONS:
      Reliabilities at Cz can reach the same level as previously reported by dipole
      source-localization methods, if sufficient sweep number and linear slopes are
      applied. SIGNIFICANCE: Based on theoretical arguments and current data, the
      continued use of the easy and rapidly done single-channel IAEP is suggested,
      although ideally in combination with multi-channel source-localization methods.
      This would be seminal for a drafted program standardizing IAEP to further improve
      its clinical utility.

PMID- 18039591
TI  - Positive slow waves in the EEG of premature infants between 24 and 36 weeks of
      conceptional age.
AB  - OBJECTIVE: The aim of this prospective and longitudinal study was to characterize
      EEG patterns during the first weeks of life in extremely premature infants.
      METHODS: Twenty-five extremely premature infants were included and weekly EEG
      recordings were obtained between 24 and 36 weeks of conceptional age (CA).
      RESULTS: Central (rolandic) positive slow waves (CPSW) were found to be the most
      reliable and characteristic pattern. CPSWs were frequent at 24 weeks CA and
      progressively diminished and disappeared around 34 weeks CA. CPSWs appeared
      isolated or in sequences, they occurred during periods of continuous or
      discontinuous EEG activity, during bursts or during intervals of discontinuous
      activity, and unilaterally or bilaterally. Temporal positive slow waves and theta
      rhythms occurred less often and did not decrease as a function of CA. In
      addition, the amount of discontinuity progressively decreased until 36 weeks CA.
      The duration of bursts stayed constant, while inter-burst intervals decreased as
      a function of CA. CONCLUSIONS: Central positive slow waves are characteristic
      features of the EEG in the extremely premature infant. SIGNIFICANCE: The presence
      of CPSWs and their progressive disappearance until 34 weeks CA may represent a
      maturational marker in the EEG.

PMID- 18039592
TI  - The influence of hostility on electroencephalographic activity and memory
      functioning during an affective memory task.
AB  - OBJECTIVE: The purpose of this study was to examine the neural correlates of
      emotional learning and hostility via the use of EEG and the Auditory Affective
      Verbal Learning Test (AAVL). METHODS: The Cook-Medley Hostility Scale (CMHO) was
      used to identify right-handed men (N=16) and women (N=44) as low or high hostile.
      Participants were administered the positive and negative word lists of the AAVL
      lists, and were asked to recall the words during a 5-trial paradigm. EEG data
      were recorded from 19 scalp sites before and following learning trials; separate
      bandwidths of the EEG spectrum were analyzed. RESULTS: As predicted, completion
      of the negative AAVL resulted in self-reported negative mood induction. Moreover,
      primacy and recency effects were demonstrated with the negative and positive
      versions of the AAVL, respectively. Unexpectedly, high hostiles demonstrated
      greater right versus left hemisphere high alpha power than low hostile
      counterparts. Low hostiles evidenced greater alpha power and low beta power than
      did high hostiles. CONCLUSIONS: These results suggest differing patterns of
      hemispheric asymmetry and overall brain activity for low and high hostiles during
      emotional learning. SIGNIFICANCE: The findings are important with regard to
      understanding the relationship between hostility, emotional learning, and
      associated neural systems.

PMID- 18039593
TI  - Changes in motor cortical excitability induced by high-frequency repetitive
      transcranial magnetic stimulation of different stimulation durations.
AB  - OBJECTIVE: To investigate the changes in cortical excitability of the human motor
      cortex induced by high-frequency repetitive transcranial magnetic stimulation
      (rTMS) of different stimulation durations. METHODS: Twenty healthy subjects
      participated in the study. Subjects received 20 trains of 10-Hz rTMS at 80% of
      the resting motor threshold (RMT) intensity with two different stimulation
      durations (5 and 1.5s) over the motor hot spot for left first dorsal interosseous
      (FDI) muscle. Electromyographic responses (motor-evoked potentials, MEPs) to
      single-pulse stimulation, and intracortical inhibition (ICI) and intracortical
      facilitation (ICF) by paired-pulse stimulation were measured bilaterally in the
      relaxed FDI muscles before, immediately after, and 30, 60, 90 and 120 min after
      rTMS. RESULTS: After 5s of 10-Hz rTMS, the mean amplitude of MEP for the
      stimulated M1 cortex decreased for up to 90min (P=0.002) and that of the
      unstimulated M1 cortex decreased for up to 60 min (P=0.008). Enhancement of ICI
      and suppression of ICF were observed and sustained for more than 90 min in both
      stimulated (P=0.001) and unstimulated (P=0.003) M1 cortex after 5s of 10-Hz rTMS.
      After 1.5s of 10-Hz rTMS, the mean amplitude of MEP increased in stimulated
      cortex for up to 120 min (P=0.005). CONCLUSIONS: With different stimulation
      durations, high-frequency subthreshold rTMS can produce different patterns of
      long-lasting changes in corticospinal and intracortical excitability in
      stimulated and unstimulated motor cortex in healthy subjects. SIGNIFICANCE: The
      results have important implications for the selection of stimulation parameters
      other than the frequency of rTMS. The clinical application of rTMS for the
      purpose of motor enhancement should be considered along with the mechanism of
      different stimulation parameters.

PMID- 18039594
TI  - Clinical neurophysiology of fatigue.
AB  - Fatigue is a multidimensional concept covering both physiological and
      psychological aspects. Chronic fatigue is a typical symptom of diseases such as
      cancer, multiple sclerosis (MS), Parkinson's disease (PD) and cerebrovascular
      disorders but is also presented by people in whom no defined somatic disease has
      been established. If certain criteria are met, chronic fatigue syndrome can be
      diagnosed. The 4-item Abbreviated Fatigue Questionnaire allows the extent of the
      experienced fatigue to be assessed with a high degree of reliability and
      validity. Physiological fatigue has been well defined and originates in both the
      peripheral and central nervous system. The condition can be assessed by combining
      force and surface-EMG measurements (including frequency analyses and muscle-fibre
      conduction estimations), twitch interpolation, magnetic stimulation of the motor
      cortex and analysis of changes in the readiness potential. Fatigue is a well
      known phenomenon in both central and peripheral neurological disorders. Examples
      of the former conditions are multiple sclerosis, Parkinson's disease and stroke.
      Although it seems to be a universal symptom of many brain disorders, the unique
      characteristics of the concomitant fatigue also point to a specific relationship
      with several of these syndromes. As regards neuromuscular disorders, fatigue has
      been reported in patients with post-polio syndrome, myasthenia gravis, Guillain
      Barre syndrome, facioscapulohumeral dystrophy, myotonic dystrophy and hereditary
      motor and sensory neuropathy type-I. More than 60% of all neuromuscular patients
      suffer from severe fatigue, a prevalence resembling that of patients with MS.
      Except for several rare myopathies with specific metabolic derangements leading
      to exercise-induced muscle fatigue, most studies have not identified a prominent
      peripheral cause for the fatigue in this population. In contrast, the central
      activation of the diseased neuromuscular system is generally found to be
      suboptimal. The reliability of the psychological and clinical neurophysiological
      assessment techniques available today allows a multidisciplinary approach to
      fatigue in neurological patients, which may contribute to the elucidation of the
      pathophysiological mechanisms of chronic fatigue, with the ultimate goal to
      develop tailored treatments for fatigue in neurological patients. The present
      report discusses the different manifestations of fatigue and the available tools
      to assess peripheral and central fatigue.

PMID- 18039595
TI  - Compound nerve conduction velocity- a reflection of proprioceptive afferents?
AB  - OBJECTIVE: To gather the required sample size to compare compound nerve
      conduction velocities (CV) to cutaneous sensory CVs and motor CVs to find out if
      there are statistically significant differences between these nerve fibre
      populations. METHODS: We report age, height, and temperature standardized CVs for
      cutaneous sensory, motor, and compound nerve fibres measured by
      electroneuromyography (ENMG) for 109 median nerves in 74 people from different
      age groups with no known neuropathy (age 50.4, median 49, range 21-87). RESULTS:
      In the region of the forearm, mean CVs were 63.6m/s (CI=62.6-64.7) for compound
      nerve fibres, 61.3m/s (CI=60.1-62.5) for cutaneous sensory fibres, and 56.3m/s
      (CI=55.1-57.6) for motor fibres (for all p<0.001). Age explained most of the
      variation of CVs (Pearson's coefficients -0.394, -0,538, and -0.443,
      respectively, for all p<or=0.002), but also height and temperature displayed
      minor explanatory effects in multivariate analysis. CONCLUSIONS: It appears that
      compound nerve CVs are faster than cutaneous sensory and motor CVs. Compound
      nerve CV may represent muscle spindle afferents. SIGNIFICANCE: These data
      contribute to an understanding of the neurophysiological mechanisms that are
      involved in normal function of the human peripheral nervous system.

PMID- 18039596
TI  - Student evaluation of a Clinical Self-Study Laboratory.
AB  - INTRODUCTION: Being clinically competent is an essential component of any nursing
      curricula to ensure that on completion the nursing graduates are able to practice
      safely and effectively as a nurse. Clinical Self-Study Laboratories have become
      increasingly popular in nursing education in recent years as a way of ensuring a
      variety of skills are taught to the nursing students. These clinical skills
      laboratories are used to teach communication and interpersonal skills,
      psychomotor skills, promote the development of collaborative skills required in
      nursing as well as being able to help integrate theory and practice [Morgan, R.,
      2006. Using clinical skills laboratories to promote theory-practice integration
      during first practice placement: an Irish perspective. Journal of Clinical
      Nursing 15, 155-161]. However, it is essential that these programs be subject to
      routine quality assurance and effectiveness evaluation. METHODOLOGY: The purpose
      of the study was to conduct a process evaluation of the implementation of the
      Clinical Self-Study Laboratory (CSSL) in the School of Nursing, University of
      KwaZulu-Natal. The process evaluation included a descriptive quantitative
      satisfaction survey of first and third year Bachelor of Nursing students, a
      checklist to assess the quality of the CSSL equipment and a retrospective record
      review of utilisation of the CSSL by students. RESULTS: The CSSL appears to be
      well implemented and utilized by students. Students reported that it was
      accessible and that the equipment in the laboratory was of a reasonable quality.
      A few students reported dissatisfaction with some of the equipment and requested
      that more equipment and trained personnel be made available.

PMID- 18039597
TI  - Laser processing of bioactive tricalcium phosphate coating on titanium for load
      bearing implants.
AB  - Laser-engineered net shaping (LENS), a commercial rapid prototyping (RP) process,
      was used to coat titanium with tricalcium phosphate (TCP) ceramics to improve
      bone cell-materials interactions. During LENS coating process, the Nd:YAG laser
      melts the top surface of Ti substrate in which calcium phosphate powder is fed to
      create a TCP-Ti composite layer. It was found that an increase in laser power
      and/or powder feed rate increases the thickness of the coating. However, coating
      thickness decreased with increasing laser scan speed. TCP coating showed columnar
      titanium grains at the substrate side of the coating and transitioned to equiaxed
      titanium grains at the outside. When the scan speed was reduced from 15 to 10mms(
      1), coating hardness increased from 882+/-67 to 1049+/-112Hv due to an increase
      in the volume fraction of TCP in the coating. Coated surfaces showed uniformly
      distributed TCP particles and X-ray diffraction data confirmed the absence of any
      undesirable phases, while maintaining a high level of crystallinity. The effect
      of TCP coating on cell-material interaction was examined by culturing
      osteoprecursor cells (OPC1) on coated surfaces. The results indicated that TCP
      coating had good biocompatibility where OPC1 cells attached and proliferated on
      the coating surface. The coating also initiated cell differentiation, ECM
      formation and biomineralization.

PMID- 18039598
TI  - Management of the neonate with chronic renal failure.
AB  - The number of infants requiring chronic dialysis is small and has remained stable
      over the last decade. The majority have structural abnormalities of the urinary
      tract and over 50% are diagnosed antenatally. Mortality rate is high,
      particularly in infants with comorbidity, but has been improving. Management
      presents many challenges: as well as ethical issues, complications of dialysis
      are common and most infants need enteral feeding. Commitment from the family and
      medical team is crucial for success. However, the long-term outcome for otherwise
      healthy infants is comparable to that of older children.

PMID- 18039599
TI  - Ultrasound-assisted removal of an airgun pellet from the hand.

PMID- 18039600
TI  - Augmentation mammoplasty: effect on diagnosis of breast cancer.
AB  - Breast augmentation for cosmetic purposes is an increasingly common procedure in
      the USA and UK. In the USA in 2003, a total of 254 140 breast augmentation
      procedures were carried out [American Society of Plastic Surgeons,
      http://www.plasticsurgery.org/news_room/Procedural-Statistics-Press-Kit
      Index.cfm9-1-2005; 2006.(1)]. It has been previously estimated that between 1 and
      1.5 million women in the USA have prosthetic breast implants [Cook RR,
      Delongchamp RR, Woodbury M, et al. The prevalence of women with breast implants
      in the United States, 1989. J Clin Epidemiol 1995;48:519-25.(2)]. The UK National
      Breast Implant Registry has recorded a rise in the numbers of women receiving
      breast implants, with over 13 000 procedures registered in 2001; an estimated 77%
      of these were for cosmetic purposes. No association has been found between the
      presence of breast implants in a breast and an increased risk of breast cancer,
      and this subject has been comprehensively reviewed elsewhere [Hoshaw SJ, Klein
      PJ, Clark BD, et al. Breast implants and cancer: causation, delayed detection,
      and survival. Plast Reconstr Surg 2001;107:1393-407.(3)]. However, as the
      population of women with breast implants ages, an increasing number of them will
      develop breast cancer; a reflection of the fact that the incidence of the disease
      increases with increasing age. Debate continues on the effect of breast implants
      on the efficacy of mammography in diagnosing breast cancer, and the role of other
      imaging techniques for this purpose, as well as the limitations that the presence
      of implants place on percutaneous biopsy techniques. We review the literature on
      the radiological and tissue diagnosis of breast cancer in women with a history of
      previous augmentation mammaplasty.

PMID- 18039601
TI  - Obesity and complications in breast reduction surgery: are restrictions
      justified?
AB  - SUMMARY: Breast reduction is effective in treating symptomatic macromastia.
      Access to surgery is sometimes limited for overweight and obese women for fear of
      complications. We studied the impact of body weight on postoperative
      complications in a consecutive series of 273 Finnish women who underwent breast
      reduction using either superior pedicle (n=94) or inferior pedicle (n=175)
      techniques; 78% of the patients were overweight (body mass index>25). An
      inferiorly based pedicle was preferred in obese and big-breasted patients
      (P<0.001), and the mean amount of resection per breast was greater using the
      inferior 2 pedicle technique (888 g vs 431 g with superior pedicle technique,
      P<0.001). Postoperative complications were frequent (52%) but overall
      complication rate did not correlate with body weight, body mass index, age,
      surgical technique or surgeon's experience (consultant vs senior registrar). The
      most common complication was delayed healing due to superficial infection (26%),
      skin necrosis or wound dehiscence (18%), followed by deep infection (8%) and
      seroma formation (8%). In obese patients, areola necrosis was more frequent than
      in patients with normal weight (6% vs 0%, P=0.007). The amount of resection and
      the distance between clavicle and areola were also associated with a risk of
      areola necrosis (P<0.05). Seromas were more frequent after superior pedicle than
      after inferior pedicle reduction (14% vs 5%, P=0.019). The use of antibiotics did
      not affect the infection risk. Surgical revisions were needed in 23% of the
      patients, for delayed healing (8.8%), haemorrhage (4.0%), deep infection (1.1%)
      and scars or puckers (13%). Reoperations were more frequent after operations
      performed by senior registrars (34% vs 16%, P=0.001). Our results indicate that
      obesity does not increase the complication risk in breast reduction surgery to
      the extent that access to reduction mammaplasty should be restricted based solely
      on body mass index.

PMID- 18039602
TI  - [2,8-dihydroxyadenine nephrolithiasis: from diagnosis to therapy].
AB  - Adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency is an enzymopathy
      of purine metabolism, which is inherited as an autosomal recessive trait. APRT is
      a salvage enzyme that normally catalyzes the conversion of adenine to adenosine
      monophosphate. APRT deficiency results in adenine accumulation with oxidation by
      xanthine dehydrogenase (XDH; EC 1.1.1.204) to 2,8-dihydroxyadenine (2,8-DHA) then
      excreted in urine. This compound is extremely insoluble and its crystallization
      can lead to stone formation and renal failure. The diagnosis of the disease is
      based on stone analysis by infrared spectroscopy or microscopic examination of
      urine, which may reveal typical 2,8-DHA crystals. The enzyme activity
      measurements in erythrocyte lysates will identify both homozygotes and
      heterozygotes for APRT deficiency. Molecular approach can identify mutations
      which are responsible of this inherited disease. Two types of deficit are
      commonly distinguished, depending on the level of residual APRT activity: type I,
      mainly observed in Caucasian subjects, in whom the enzyme activity is
      undetectable in homozygous patients and type II, found in Japanese patients who
      are able to form APRT but the enzyme activity is strikingly reduced because a low
      affinity for phosphoribosylpyrophosphate. The crystallization of 2,8-DHA and
      subsequent renal damages may be prevented with allopurinol therapy, a xanthine
      oxidase inhibitor. The role of the laboratory is crucial to detect APRT
      deficiency and to assess the efficacy of therapy, the objective being to avoid
      2,8-DHA crystal formation.

PMID- 18039603
TI  - [Clinical and epidemiological characterization of infections due to imipenem
      resistant Acinetobacter baumannii at the university hospital Sahloul, Tunisia].
AB  - OBJECTIVE: to characterize epidemiological and clinical features related to the
      multi-drug Acinetobacter baumannii infections in the university hospital Sahloul
      in Tunisia. MATERIAL AND METHODS: retrospective study including twenty-four
      imipenem resistant Acinetobacter baumannii isolated from twenty patients
      hospitalized in different wards of the hospital. Study of clinical features
      related to the infection by multi-drug Acinetobacter baumannii, bacterial
      identification by classical identification scheme, antibiotic susceptibilities
      were determined by the disk diffusion method; genotyping was performed by
      arbitrarily-primed PCR. RESULTS: the most incriminated ward was the intensive
      care unit with a high prevalence of septicaemia. All studied strains were multi
      drug to all beta-lactams tested. Genotyping has shown the clonality of studied
      strains. Features incriminated in the acquisition of infection were essentially
      immunodeficiency, invasive manoeuvring and antibiotherapy. CONCLUSION: multidrug
      Acinetobacter baumannii is increasingly isolated in our hospital. Rational use of
      antibiotics and rigorous application of hygienic rules could contribute to limit
      dissemination of such strains.

PMID- 18039604
TI  - [Comparison of five techniques to detect anti-Saccharomyces cerevisiae antibodies
      (ASCA) in serum for diagnosing Crohn's disease].
AB  - OBJECTIVE: the anti-Saccharomyces cerevisiae antibodies (ASCA) are diagnostic
      markers found in Crohn's disease patients. The aim of this study was to compare
      three Elisa (enzyme linked immunosorbent assay) kits with the indirect
      immunofluorescence (IFI) technique and an immunodot for ASCA detection. MATERIALS
      AND METHODS: we compared the results obtained using IFI (IgA and IgG) and Elisa
      (IgA and IgG) in 139 patients (37 Crohn's disease). An immunodot (IgA+IgG) was
      tested in a sub-group of 24 patients (18 Crohn's disease). RESULTS AND
      DISCUSSION: for the different techniques by Elisa (IgA or IgG), the sensitivity
      ranged from 65% to 76%, the specificity from 88% to 98%, the positive predictive
      value (PPV) from 84% to 94% and the negative predictive value (NPV) from 88% to
      93%. For IFI, the sensitivity was 81%, the specificity 100%, the PPV 100% and the
      NPV 93%. The immunodot showed a specificity and PPV of 100% and NPV of 33%.
      CONCLUSION: the detection of the ASCA is useful in the diagnosis of Crohn's
      disease. IFI appears as the method of choice for its excellent sensitivity and
      specificity, and affordable costs.

PMID- 18039605
TI  - [Feto-maternal metabolism in human normal pregnancies: study of 73 cases].
AB  - From 73 normal pregnancies of gestational age between 17 and 41 weeks of
      gestation (WG), the concentrations of glucose, pyruvate and lactate, free fatty
      acids, ketone bodies (aceto-acetate and beta-hydroxybutyrate) and cholesterol
      were assessed on maternal venous blood (MVB) and umbilical venous blood (UVB),
      sampled by cordocentesis. The objective of this work was to study feto-maternal
      metabolism, as well as nutritional exchange between maternal blood and fetal
      blood during the second and third trimesters of pregnancy. Maternal and fetal
      glycemias, as well as maternal-fetal glucose concentration gradient, were found
      stable during the studied gestational period; maternal glucose is always higher
      than fetal glucose, with a mean concentration delta of 0.69+/-0.34 mmol/L.
      Maternal lactate level (1.26+/-0.38 mmol/L) is lower than fetal lactate level
      (1.48+/-0.46 mmol/L), whereas maternal blood pyruvate concentration (0.042+/
      0.020 mmol/L) is higher than fetal blood pyruvate concentration (0.025+/-0.010
      mmol/L). Consequently, mean lactate / pyruvate ratio is found twice lower in
      maternal blood (31.77+/-9.89) than in fetal blood (64.10+/-17.12). Free fatty
      acids concentration is approximately three times higher in maternal blood than in
      fetal blood (respectively 0.435+/-0.247 mmol/L and 0.125+/-0.046 mmol/L).
      Maternal venous aceto-acetate (0.051+/-0.042 mmol/L) and beta-hydroxybutyrate
      (0.232+/-0.270 mmol/L) concentrations are significantly lower than those in UVB
      (respectively 0.111+/-0.058 and 0.324+/-0.246 mmol/L) and the beta
      hydroxybutyrate/aceto-acetate ratio is on average 1.7 times higher in MVB (4.75+/
      2.5) than in UVB (2.82+/-1.18). Cholesterol concentration is significantly higher
      in maternal blood (6.26+/-1.40 mmol/L) than in fetal blood (1.66+/-0.34 mmol/L).
      Our results show the characteristics of oxidative metabolism of the fetus
      compared with that of the adult. Blood concentration in energy substrates,
      measured with glucose and free fatty acids levels, is low in UVB and suggests
      increased energy needs of the growing fetus. Mean high concentrations in aceto
      acetate and beta-hydroxybutyrate in UVB, indicate probably fetal ketogenesis. UVB
      low cholesterolemia suggests high cholesterol consumption in the fetal
      compartment for cellular membrane synthesis and steroid biosynthesis.

PMID- 18039606
TI  - [Molecular phylogeny and genetic variability of echovirus 30 based on the
      analysis of the 3' end of the VP1 gene].
AB  - Echovirus 30 represent one of the most frequently isolated enterovirus serotype,
      incriminated in various pathologies, essentially aseptic meningitis. Several
      works studied the molecular epidemiology of these viruses. By analysing a region
      of 260 nucleotides situated in the end of the VP1 gene (region regrouping the
      majority of the sequences of the Echovirus 30), we proposed to realise a
      synthesis work which regroup the main epidemiological studies on the Echovirus
      30. We established a phylogenetic profile of 87 Echovirus strains geographically
      distinct and isolated during a half a century (1957-2003). The phylogentic tree
      permitted to distinguish 2 genogroups which the nucleotide divergence exceeds
      20%. The 2 genogroups also present internal subdivisions named genotypes which
      the nucleotide divergence is more than 15%. Finally, we noted phylogenetic
      regroupings within a same genotype. The general profile of the phylogenetic tree
      is characterised by a distribution of the Echovirus 30 strains in the time
      independently of their geographically isolation, which reveals a genetic
      evolution of these viruses related to their high genetic plasticity and the rapid
      circulation from a geographic area to another.

PMID- 18039607
TI  - [Immunoquantification of serum lipoprotein(a) in healthy Ivorian subject: a
      comparative evaluation of two methods].
AB  - We have determined the concentration of Lp(a) in an Ivory Coast population
      (n=102) using two immunochemical methods: Laurell's monodimensional electro
      immunodiffusion (EID) and immunonephelometry (IN). Within-run and between-run
      precision was respectively 3.07% and 3.97% by IN and 1.52% and 4.48% by EID
      method. As regard the exactitude, the bias goals in two methods were 3.5% and
      3.0% respectively with IN and EID. The two methods were correlated (r=0.84;
      p=0.006). Mean values of Lp(a) were significantly (p=0.0007) higher by IN than
      EID: 0.48+/-0.34 g/L versus 0.32+/-0.19 g/L. The Lp(a) distributions were non
      Gaussian, skewed towards high values, with median value of 0.47 g/L and 0.32 g/L
      respectively for IN and EID methods. Therefore, we conclude that although both
      methods showed a satisfactory precision, and results were correlated, Lp(a)
      values were higher by INP. Furthermore, mean values of Lp(a) in presumed healthy
      Ivorian is higher than in Caucasians.

PMID- 18039608
TI  - [Bone marrow necrosis in two patients with neoplastic disorders].
AB  - Bone marrow necrosis is defined by extensive necrosis of the myeloid tissue and
      bone marrow stroma. Diagnosis is done on characteristic cytological pattern of
      the bone marrow aspiration and/or biopsy. We report two observations. The first
      patient, aged 75, has been hospitalized for fever, asthenia and lower back pain.
      An haematological malignancy was suspected after observation of a few peripheral
      blood blast cells, but necrosis was found on the bone marrow aspiration and could
      not lead to further haematological diagnosis. Within next days, the white blood
      cell count and the number of blasts increased, leading to the diagnosis of acute
      monoblastic leukaemia. A chemotherapy was started but the patient died 20 days
      after admission. The second patient, aged 28, has been hospitalized for severe
      bleeding a few days after the diagnosis of a metastatic gastric tumour. The bone
      marrow aspiration, made for the evaluation of a thrombocytopenia, showed a
      massive necrosis. The patient deceased shortly after hospitalization. According
      to literature, bone marrow necrosis is in most instances secondary to either an
      haematological malignancy (60%) or to a solid tumour (30%), but only at times
      observed with a non-malignant disorder. Bone pain, fever, cytopenias and elevated
      serum lactic dehydrogenase and alkaline phosphatase are frequently reported, but
      are mostly non specific of the diagnosis in these malignant conditions.
      Examination of the bone marrow leads to the diagnosis: cells are pycnotic,
      scarcely recognizable in a background of amorphous extracellular eosinophilic
      proteinaceous material, and histology shows disappearance of fat spaces with
      preservation of the bone tissue. Tissue hypoxemia due to microcirculation failure
      may be the main mechanism leading to the necrosis, whatever the related disorder.
      Supportive care together with specific therapy of the causal disease must be
      started promptly. The prognosis depends on the underlying illness and is
      generally very poor when extensive necrosis is observed.

PMID- 18039609
TI  - [Kidney vasculitis connected to cryoglobulinemia IIA and hepatitis B].
AB  - We report the case of a 70 years old patient hospitalized for renal insufficiency
      and deterioration of the general state. The electrophoresis of serum proteins on
      freezing of agarose reveals the presence of a discrete peak of monoclonal pace on
      the level of the gammaglobulines identified by serum immunofixation like IgM of
      the kappa type. The research of the cryoglobulinemia carried out in a laboratory
      of city was made positive and typified like a monoclonal cryoglobulinemia IgM
      kappa, thus directing the diagnosis towards a disease of Waldenstrom. However,
      the result of the biopsy medullary made exclude any lymphoproliferatif syndrome.
      The positivity of the serology of hepatitis B justified a second request for
      study of the cryoglobulinemia, carried out within our laboratory. The
      cryoglobuline was typified like mixed (IgM kappa monoclonal and IgG
      polyclonales). This result associated with the immunological assessment and the
      renal biopsy made retain for our patient the diagnosis of a kidney vasculitis
      connected to an infection chronicle by the virus of hepatitis B. This observation
      points out the interest of the preanalytic, analytic and post analytic phases in
      the study of the cryoglobulinemias. A good technical control is today the only
      guarantee of the quality of the result of this examination which has large
      importance in internal medicine in the etiologic assistance with the diagnosis of
      certain clinical demonstrations.

PMID- 18039610
TI  - [Biochemical and molecular diagnosis of Gaucher disease in Tunisia].
AB  - Our study was carried out at a family from the Sahel (Tunisia). The father (index
      case) and his two children (son and daughter). The father beta-glucocerebrosidase
      (GCB) activity showing a deficit. These biochemical analyses are supplemented by
      molecular studies: enzymatic digestion and the direct sequencing. Two mutations
      were analysed, the p.Asn 370 Ser and the p.Leu 444 Pro. The DNA sequencing
      confirmed the presence of the homozygous genotype of this p.Asn 370 Ser in the
      father DNA and the heterozygous one in the two children DNA. It has no detection
      of the 55 pb deletion in exon 9 among all the specimens of DNA treated. The
      mutation p.Asn 370 Ser is associated with Gaucher disease type 1 correlated of a
      total absence of neurological involvements.

PMID- 18039611
TI  - [Early detection of leptomeningeal metastasis in patients with metastatic breast
      carcinoma: validation of CA 15-3 measurement in cerebrospinal fluid].
AB  - Fifteen per cent of metastatic breast cancer will develop symptomatic
      leptomeningeal metastases. The introduction of trastuzumab (Herceptin) therapy
      has improved the response rates of survival of patients with metastatic breast
      cancer overexpressing HER2. Although previous studies are retrospective and of
      limited number, involving small study groups and different types of patient
      management, several authors have reported a 30% incidence of leptomeningeal
      metastases in patients with metastatic breast cancer overexpressing HER2 who were
      treated with trastuzumab, while 70 to 80% of cases of the disease were controlled
      systemically. In order to improve control of the disease at the level of the
      central nervous system (CNS), routine detection of leptomeningeal metastases in
      high-risk patients could be offered. CA 15-3 in cerebrospinal fluid (CSF)
      detection might be useful in helping to diagnose CNS metastases, particularly
      where cytology results are negative--which applies to 30% of cases--because tumor
      markers are more sensitive in detecting the tumor process. Our study validate CA
      15-3 measurement in CSF and reference values were given.

PMID- 18039612
TI  - [Monoclonal IgM interference with immunoturbidimetric determination of ferritin
      and transferrin].
AB  - When they are present in important blood concentration, the monoclonal
      immunoglobulins are known to interfere with many immuno-analyze assays. We report
      the case of a patient presenting a Waldenstrom macroglobulinemia, for which the
      determination of some parameters of the martial assessment was impossible because
      of the presence of IgM kappa. The analysis of analytical alarms of the automat as
      well as the installation of simple and fast pre-treatment protocol of the
      interference enabled us to quickly make a result useful for the management of
      this patient.

PMID- 18039613
TI  - [Contribution of the genetic fingerprintings compared to grouping ABO/Rhesus
      technique in the expertise of filiation].
AB  - Paternity is based on biological analyzes that have drastically developed during
      the past 20 years. According to scientific developments, paternity testing was
      based on red blood groups studies, the analysis of red cell enzymes and plasma
      proteins polymorphisms, the typing of the HLA antigens, and the DNA polymorphism
      in its various forms. This study aims at comparing two analyses: red blood groups
      and DNA polymorphism. The performance of each test is analyzed in this report,
      based on a study of 142 cases. Indeed, the numbers of case of paternity exclusion
      are respectively 6 and 45 by the classic method and the genetic one. Thanks to
      studies based on the gene amplification of microsatellites, the efficiency of
      this reference technique has been proved, however, the classic one makes it
      possible in the cases of exclusion to lead to a certain decision without recourse
      to other systems. Of these facts, beyond the most efficient biological analysis,
      it is very important to think about paternity testing as a process in which
      biological tests are only one step.

PMID- 18039614
TI  - [Statistical comparison of the results of the blood cells count obtained with a
      Micros 60 ABX analyzer using the genuine reagents and generics reagents kits].
AB  - Using the haematology automated analyser Micros 60 (Horiba ABX, Montpellier,
      France), the results of the blood cells count obtained with the generic reagents
      kit made by SFRI Company (Saint-Jean d'Illac, France, www.sfri.com) have been
      compared with the results obtained with the genuine reagents supplied by Horiba
      ABX Company. MATERIALS AND METHOD: 50 whole blood samples (EDTA tubes) collected
      during the blood donation procedures were used after their biological tests in
      the blood bank, for the statistical study. Linearity, correlation coefficients,
      coefficient of variation (CV), means and DS were calculated and compared.
      RESULTS: overall correlations calculated between the both reagents kits were
      excellent. No statistical differences were found comparing the means, linearity
      and CV. These results were suggesting that uses of these generic reagents kits
      sensibly were able to improve the ratio Price Quality of the blood cell counts in
      routine.

PMID- 18039615
TI  - [About the choice of acceptability limits in external quality assessment
      schemes].
AB  - Quality control schemes are a practical tool used in clinical laboratories and an
      essential element for any quality assurance process. In France, external quality
      assessment schemes (EQAS) can be mandatory (as national quality control organized
      by AFSSAPS) or voluntary as those suggested by French associations (ProBioQual,
      CTCB or Asqualab). These EQAS usually evaluate participants according to their
      performances: this ranking depends on acceptability limits which are here
      compared. Various examples based on ProBioQual's background illustrate
      difficulties to plan out analytical quality specifications. A comment is given
      about the best criteria (state of the art or biological variation mainly) to be
      considered to delimit analytic goals. This discussion includes approaches
      suggested by French committee on accreditation (Cofrac). All criteria could be
      criticized but it is important to compare oneself laboratory to peers and also to
      take account of biological variation.

PMID- 18039616
TI  - [Metabolic therapy for early treatment of age-related macular degeneration].
AB  - Currently, age-related macular degeneration is one of the most common eye
      diseases causing severe and permanent loss of vision. This disease is estimated
      to affect approximately 300-500 thousand Hungarians. While earlier no treatment
      was available, in the recent decade an antioxidant therapy became very popular
      using combinations of high dosage antioxidant vitamins C, E, beta carotene and
      zinc. Based on theoretical concepts and mostly in vitro experiences, this
      combination was thought to be effective through neutralizing reactive oxygen
      species. According to a large clinical trial (AREDS) it reduced progression of
      intermediate state disease to advanced state, but did not influence early
      disease. This original combination, due to potential severe side effects, is not
      on the market anymore. However, the efficacy of modified formulas has not been
      proved yet. Recently, the metabolic therapy, a combination of omega-3 fatty
      acids, coenzyme Q10 and acetyl-L-carnitine has been introduced for treating early
      age-related macular degeneration through improving mitochondrial dysfunction,
      specifically improving lipid metabolism and ATP production in the retinal pigment
      epithelium, improving photoreceptor turnover and reducing generation of reactive
      oxygen species. According to a pilot study and a randomized, placebo-controlled,
      double blind clinical trial, both central visual field and visual acuity slightly
      improved after 3-6 months of treatment and they remained unchanged by the end of
      the study. The difference was statistically significant as compared to the base
      line or to controls. These functional changes were accompanied by an improvement
      in fundus alterations: drusen covered area decreased significantly as compared to
      the base line or to control. Characteristically, all these changes were more
      marked in less affected eyes. A prospective case study on long-term treatment
      confirmed these observations. With an exception that after slight improvement,
      visual functions remained stable, drusen regression continued for years.
      Sometimes significant regression of drusen was found even in intermediate and
      advanced cases. All these findings strongly suggested that the metabolic therapy
      may be the first choice for treating age-related macular degeneration. Currently,
      this is the only combination of ingredients corresponding to the recommended
      daily allowance, and at the same time, which showed clinically proved efficacy.

PMID- 18039617
TI  - [Liver resection for living-donor liver transplantation: anesthesia and intensive
      care aspects].
AB  - The living related donor mortality after liver donation could occur as a result
      of postoperative cardiovascular and thromboembolic complication; which could be
      minimized by detailed preoperative assessment of the living donor. The
      preoperative functional tests evaluate the physiological reserve or identify the
      living donors with limited response to the surgical stress. Based on the results
      of CT volumetry, MRI and liver functional reserve capacity test (indocyanine
      green retention ratio) the liver resection can be done safely. The preoperative
      cytochrome P enzymes tests of donors identify the drugs with abnormal metabolism.
      Balanced anesthesia combined with thoracic epidural anesthesia is done with liver
      safe, renal safe and ischemic preconditioning drugs. Normovolemic state is
      maintained with physiologic extrahepatic perfusion and oxygenation conditions.
      The central venous and hepatic artery pressure is reduced with the guarantee of
      optimal hepatic perfusion-oxygenation and better liver resection condition.
      Intraoperative thrombosis prophylaxis is performed with sequential compression
      device. After liver resection the donor morbidity can be reduced, effective
      analgesia, thrombosis prophylaxis, liver safe drug therapy and a tight
      monitoring. Before the first postoperative mobilization a deep vein Doppler
      ultrasound control is proposed.

PMID- 18039618
TI  - [Molecular biological virus identification in dilated cardiomyopathy].
AB  - Enteroviruses have been considered to be the most common cause of acute
      myocarditis and possible consequence of dilated cardiomyopathy. Some publications
      shed light to the role of other viruses in this disease as well. Our molecular
      investigation has demonstrated that adeno- and herpes viruses might also
      frequently occur in dilated cardiomyopathy. AIM: The aim of our study was to
      screen virus genomes in heart tissues from heart-transplanted patients to prove
      their possible role in the pathogenesis of dilated cardiomyopathy. METHODS: DNA
      and RNA were isolated from five regions of the heart muscle. Amplification for
      Adenovirus Type 3, Human Herpes Virus Type 6 and Enterovirus genomes were
      performed by nested-Polymerase Chain Reaction. Finally the virus-positive samples
      were direct sequenced. RESULTS: In 2 patients Adenovirus Type 3 and in 1 patient
      both Adenovirus Type 3 and Human Herpes Virus Type 6 were detected. No
      enteroviruses were found in any heart tissue. CONCLUSIONS: In our study the
      adenovirus genome was found to be the most frequent virus genome in explanted
      heart tissues. The identified viral sequences proved previous viral infection,
      which could have played a role in the development of dilated cardiomyopathy.
      Detection of different viruses in the myocardium by molecular biological
      examinations might contribute to adequate treatment of these patients.

PMID- 18039619
TI  - [Life expectancy of extremely preterm infants].
AB  - Extremely preterm infants [gestational age (GA) between 24-28 weeks] should be
      delivered optimally in an institute where neonatal intensive care unit (NICU) is
      available and their short- and long-term care is ensured. At the Department of
      Obstetrics and Gynecology, Medical School, University of Pecs, 7499 infants were
      born between 1st of January, 2000 and 31st of December, 2004. During this period
      the rate of preterm deliveries was 20% (1499/7499). Among preterm infants the
      incidence of extremely preterm babies (GA 28 weeks or less) was 18% (272/1499),
      the rate of profoundly preterm infants (GA less than 25 weeks) was 3.2%
      (48/1499). Advancing with gestational age the survival rate is increasing. At the
      department, the rate of handicapped infants among extremely premature babies was
      15.3%. The majority of the handicapped infants were profoundly preterm,
      meanwhile, more than 50% of infants born at the 26 gestational weeks were free of
      symptoms influencing social activities. It is important to stress the prognostic
      value of the screening for hearing loss (otoacoustic emission), visual problems,
      and intracranial bleeding for the early detection and cure of the possible
      complications of prematurity.

PMID- 18039620
TI  - [Cystic struma ovarii, a rare form of ovarian tumor--case report, and review of
      the literature].
AB  - Struma ovarii represents less than 3% of ovarian teratomas. It can be associated
      with thyroid biology abnormalities, and in exceptionally rare cases it can be
      malignant. The authors report a case of a 31-year-old woman who underwent
      resection of a left ovarian cyst, presenting with the clinical features of an
      ovarian cancer (large pelvic mass, ascites and elevated CA-125 serum levels). The
      pathologic diagnosis was benign struma ovarii. The postoperative thyroid function
      remained normal.

PMID- 18039621
TI  - [Anton Masch and the Polyglotton Medicum].

PMID- 18039626
TI  - Factors in consistency between attitudes and behavior: implications for policies
      and programs. 1981-82.

PMID- 18039627
TI  - Barriers to care seeking in directly observed therapy short-course (DOTS) clinics
      and tuberculosis control in southern Nigeria: a qualitative analysis.
AB  - An understanding of the socioeconomic and cultural realities of persons infected
      with tuberculosis (TB) in communities is important to re-strategizing control
      programs because these realities often come as constraints to the use of the
      directly observed therapy short-course (DOTS) in Nigeria. In-depth interviews and
      focus group discussion were used to study barriers to attendance at DOTS clinics
      for both prompt diagnosis and treatment of smear positive cases in Nigerian
      communities. A number of common and interrelated factors form barriers to use of
      DOTS clinics. These include perceived causes of the infection, for example
      witchcraft, that mitigate against an orthodox solution to TB and thereby affect
      perceived efficacy of DOTS. Another factor is perceived high cost in resource
      poor settings. Facility staff were noted to have demanded money from patients in
      spite of the fact that DOTS is advertised as free treatment. Furthermore,
      community members complain of the hostile attitude of health staff toward poor
      people as a barrier to community use of the facilities. It follows, therefore,
      that the attitude of health workers must be addressed if community members will
      use the DOTS clinics.

PMID- 18039628
TI  - Self-perception of body weight, weight management practices and goals, and other
      weight-related factors in central and eastern European adolescents.
AB  - Self-perception of body weight, management practices and goals, and other weight
      related factors were assessed among a sample of 2,566 adolescents from 30 high
      schools in Hungary, Slovakia, Czech Republic, Romania, Ukraine, and Poland.
      Students who perceived themselves as much too fat were more likely than those
      with other weight perceptions to engage in weight management practices to lose
      weight, have higher body mass index, rate themselves lower on physical
      attractiveness, and estimate higher percentages of their same-sex friends as
      trying to lose weight. Similar to other research, boys and girls differed on self
      perception of weight and other weight-related factors. Cross-cultural comparisons
      between central and eastern European adolescents and U.S. adolescents, as well as
      east and southeast Asian youth are made. Implications for health education
      practice are discussed.

PMID- 18039629
TI  - Role of social support, hardiness, and acculturation as predictors of mental
      health among international students of Asian Indian origin.
AB  - This study determined the role of social support, hardiness, and acculturation as
      predictors of mental health among international Asian Indian students enrolled at
      two large public universities in Ohio. A sample of 185 students completed a 75
      item online instrument assessing their social support levels, acculturation,
      hardiness, and their mental health. Regression analyses were conducted to test
      for variance in mental health attributable to each of the three independent
      variables. The final regression model revealed that the belonging aspect of
      social support, acculturation and prejudice of acculturation scale, and
      commitment and control of hardiness were all predictive of mental health (R2 =
      0.523). Recommendations have been offered to develop interventions that will help
      strengthen the social support, hardiness, and acculturation of international
      students and help improve their mental health. Recommendations for development of
      future Web-based studies also are offered.

PMID- 18039630
TI  - Exercise, blood sugar, blood pressure, and cholesterol levels in a Caribbean
      population.
AB  - This study used a population-based sample of 407 Seventh-day Adventists in
      Barbados to determine the relationship between physical activity, blood sugar,
      hypertension, and cholesterol levels. A systematic random sampling technique was
      used to select participants: 37.6% were male and 62.4% female. No significant
      association was found between exercise and the outcome variables: blood sugar,
      blood pressure, and cholesterol levels of participants. However, females appeared
      to be more sedentary when compared to males. A significant association was seen
      between weekly exercise and triglycerides, but only in male participants.

PMID- 18039631
TI  - African women and vulnerability to HIV/AIDS: implications for female related
      cultural practices.
AB  - Violence against women in Africa dates back to primordial society, where cultural
      practices such as female genital mutilation and polygamous marriages were
      prescribed and supervised by male-dominated social structures. Women's status has
      always been at high risk, since such practices are male supervised. With the
      upsurge of the HIV/AIDS pandemic globally, research needs to focus on such
      cultural practices, the dangers of such practices, and possible eradication. The
      present article examines the change-resistant, prevailing religious, social, and
      psychological barriers to change.

PMID- 18039632
TI  - Innovative approaches in the treatment and support of patients with acute
      myelogenous leukemia.

PMID- 18039633
TI  - Difficulties with fungal infections in acute myelogenous leukemia patients:
      immune enhancement strategies.
AB  - Invasive fungal infection in severely immunosuppressed patients with acute
      myelogenous leukemia (AML) remains a serious challenge because (a) of the higher
      rates of non-drug susceptible fungal sinopulmonary disease; (b) despite advances
      in diagnostic fungal assays, the correct identification of causative organism(s)
      is difficult, and antifungal drug susceptibility data are seldom available during
      clinical decision making; and (c) the increasing frequencies of zygomycosis,
      scedosporiosis, and highly virulent Candida tropicalis infection have undermined
      the gains attributed to effective anti-Aspergillus drug therapy. Recombinant
      cytokines, such as recombinant human (rh)GM-CSF and interferon (IFN)-gamma, have
      been explored to augment host antifungal immune responses. These cytokines
      promote activation and recruitment of granulocyte and mononuclear phagocytic
      effector cells. Prophylaxis with rhGM-CSF was associated with significantly fewer
      life-threatening and serious (grade > or =3) infections, especially in older
      patients undergoing treatment for AML. The limited experience with rhGM-CSF for
      the treatment of invasive fungal infections in combination with antifungal
      drug(s) was associated with a favorable outcome, and in contrast to Escherichia
      coli-derived rhGM-CSF, the new preparation (sargramostim) was well tolerated and
      rarely associated with serious systemic toxicities. Similarly, IFN-gamma has been
      successfully used in patients with antimicrobial drug-refractory and/or
      disseminated fungal infection. Most patients tolerate the T-helper type 1
      protagonist cytokine without serious adverse events. In difficult-to-treat fungal
      infections, the addition of cytokines appears to improve outcome and may be
      considered early in severely immunosuppressed patients with AML.

PMID- 18039634
TI  - Role of macrophages in host defense against aspergillosis and strategies for
      immune augmentation.
AB  - Invasive aspergillosis is a major cause of morbidity and mortality in highly
      immunocompromised patients with cancer. Alveolar macrophages ingest inhaled
      conidia (spores). Through pathogen recognition receptors that ligate fungal cell
      wall motifs, macrophages are able to coordinate the inflammatory response to
      Aspergillus species. Macrophages and dendritic cells play an important role in
      regulating the balance between the proinflammatory and anti-inflammatory cytokine
      responses that are required for recruitment and activation of neutrophils, and in
      augmenting or attenuating cellular immunity. Macrophages are therefore a target
      for immune augmentation strategies that include administration of cytokines,
      colony-stimulating factors, and pathogen recognition receptor ligands.

PMID- 18039635
TI  - Recent developments in acute myelogenous leukemia therapy.
AB  - Recent progress has been made in several areas in the treatment of acute
      myelogenous leukemia (AML): prognostic factors, allogeneic bone marrow
      transplantation, and new and targeted therapies. Delineation and clarification of
      prognostic factors have led to improved risk determination, with research moving
      from cytogenetics to an examination of molecular markers. Trends in the area of
      allogeneic bone marrow transplantation include broad adoption of reduced
      intensity conditioning despite the lack of prospective comparative studies.
      Although the preponderance of data has established this as a feasible option, a
      true understanding of how much of an advantage it conveys needs to be established
      in prospective studies. The use of alternative donors is another advance, and
      recent data are promising, but survival is poor if transplantation is performed
      when disease is active, especially during refractory relapse or refractory
      disease. When haploidentical matched donors are used, survival rates appear
      similar to those reported with matched unrelated-donor transplants. Analysis of
      the data for allogeneic transplantation shows that HLA-identical sibling
      transplants to patients in the first complete remission (CR1) provide the highest
      probability of long-term survival, compared with HLA-identical sibling
      transplants to patients in later remissions. Similarly, unrelated-donor
      transplants to high-risk patients in CR1 lead to a greater degree of success than
      unrelated-donor transplants to patients in CR2 or later remission. Cord blood has
      also been established as a suitable source for hematopoietic transplantation in
      AML. A third area of recent progress involves new and targeted therapies.
      Multiple new agents with tremendous potential are in development and clinical
      trials. Therapy can even be tailored to several specific genetic subtypes of AML.

PMID- 18039636
TI  - The role of sargramostim (rhGM-CSF) as immunotherapy.
AB  - GM-CSF stimulates the differentiation of hematopoietic progenitors to monocytes
      and neutrophils, and reduces the risk for febrile neutropenia in cancer patients.
      GM-CSF also has been shown to induce the differentiation of myeloid dendritic
      cells (DCs) that promote the development of T-helper type 1 (cellular) immune
      responses in cognate T cells. This review summarizes some of the immunological
      effects of GM-CSF relevant to antitumor immunity in cancer patients. GM-CSF has
      been used to augment the activity of rituximab in patients with follicular
      lymphoma and to induce autologous antitumor immunity in patients with hormone
      refractory prostate cancer. GM-CSF causes upregulation of costimulatory molecule
      expression on leukemia blasts in vitro, enhancing their ability to present
      antigen to allogeneic T cells, and, in combination with interferon-alpha, can
      induce antitumor immune responses in patients whose acute leukemia has relapsed
      following allogeneic hematopoietic progenitor cell transplant. Tumor cells
      engineered to secrete GM-CSF are particularly effective as antitumor vaccines,
      and the addition of GM-CSF to standard vaccines may increase their effectiveness
      by recruiting DCs to the site of vaccination. However, a significant limitation
      in the use of GM-CSF as an immunostimulatory agent is that objective antitumor
      responses are infrequent, and are often not durable. Effective and durable
      antitumor immunity will likely require novel methods to eliminate
      counterregulatory immune responses that limit activation and expansion of
      cytotoxic T cells with antitumor activity.

PMID- 18039637
TI  - Effectiveness of computed tomography to evaluate central giant cell lesion.
AB  - Central giant cell lesion (CGCL) is a benign disease involving the mandible (70%)
      more than the maxilla; it tends to be more common in women. Clinically, the
      lesion may be associated with pain, tooth displacement, facial asymmetry,
      paraesthesia and ulceration of the mucosa. The radiographic aspect of CGCL is
      highly variable since it may appear as a unilocular or multilocular radiolucent
      area with expansion and perforation of the cortical bone. Few previous reports
      have dealt with the usefulness of CT in the evaluation of this lesion. The
      purpose of this study is to report the clinical and imaging features of a case,
      including CT, treated by a conservative method.

PMID- 18039638
TI  - Oxidative stress and ferritin levels in haemodialysis patients.
AB  - BACKGROUND: Increased oxidative stress (OS) and inflammation are associated with
      atherosclerotic coronary artery disease in haemodialysis (HD) patients. Ferritin
      may have other effects in addition to its role in storing intracellular iron.
      This study was performed to determine any relationships between markers of OS,
      nutrition and inflammation in HD patients with normal and high ferritin levels.
      METHODS: Our cohort comprised 34 maintenance dialysis patients on erythropoietin
      therapy and 22 healthy controls. HD patients were divided into two groups: 17
      with normal (<800 ng/ml) and 17 with high (>800 ng/ml) ferritin levels, and we
      measured lipid profile, albumin, highly sensitive C-reactive protein (hsCRP),
      anti-oxidant enzymes [whole blood glutathione peroxidase (Gpx), serum superoxide
      dismutase (SOD), paraoxonase, arylestherase (AE) and total anti-oxidant status
      (TAOC)], anti-oxidants (vitamin C) and lipid peroxidation products [red blood
      cell malondialdehyde (RBC MDA)]. RESULTS: Compared with controls, the HD patients
      had higher serum urea, blood pressure, triglyceride, hsCRP, RBC MDA, SOD and TAOC
      values and lower albumin, low-density lipoprotein cholesterol, apolipoprotein AI,
      paraoxonase, AE and whole blood Gpx activities. Serum vitamin C, uric acid,
      apolipoprotein B, total- and high-density lipoprotein cholesterol, apolipoprotein
      B MDA, and lymphocyte levels in the HD patients with normal and high ferritin
      levels were similar. The OS markers of HD patients did not differ, whether or not
      they received intravenous iron supplementation or had transferrin saturations <
      50% or > or = 50%. CONCLUSION: HD patients are in a higher oxidative state, which
      results in the reduction of total anti-oxidant capacity and also have an
      increased inflammation status. We could not find a relationship between ferritin
      level and OS markers in HD patients receiving erythropoietin.

PMID- 18039639
TI  - Towards the prevention of bone fractures in dialysed patients?

PMID- 18039640
TI  - Acute kidney injury due to deferoxamine in a renal transplant patient.

PMID- 18039641
TI  - After several years of witchhunting, can calcium-based phosphate binding be
      released on probation?

PMID- 18039642
TI  - Predictors of new-onset decline in kidney function in a general middle-european
      population.
AB  - BACKGROUND: Limited epidemiological data are available on predictors of new-onset
      kidney disease. METHODS: In this longitudinal cohort study, 17 375 apparently
      healthy volunteers of the general Viennese population (46.4% women, age range 20
      84 years, men 20-89 years) performed a baseline examination at some time within
      the study period (1990-2005) and completed a median of two follow-up examinations
      [interquartile range (IQR) 1 to 4]; the median follow-up period was 7 years (IQR
      4 to 11). The outcome of interest was the development of kidney disease, defined
      as a decrease of the glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) at the
      follow-up examinations [calculated by the abbreviated modification of diet in
      renal disease (MDRD) equation]. Logistic generalized estimating equations were
      used to analyse the relationship between the covariates and the outcome variable.
      RESULTS: The following parameters [odds ratios (OR) with 95% confidence
      intervals] predicted new-onset kidney disease: Age (increase by 5 years), OR =
      1.36 (1.34-1.40); National Kidney Foundation-chronic kidney disease (NKF-CKD)
      stage 1 with proteinuria (+), OR = 1.39 (1.10-1.75); NKF-CKD stage 1 with
      proteinuria (>/=++), OR = 2.07 (1.11-3.87); NKF-CKD stage 2 with proteinuria (+),
      OR = 2.71 (2.10-3.51); NKF-CKD stage 2 with proteinuria (>/=++), OR = 3.80 (2.29
      6.31); body mass index, OR = 1.04 (1.02-1.06); current-smoker, OR = 1.20 (1.01
      1.43); performing no sports, OR = 1.57 (1.27-1.95); uric acid (increase by 2
      mg/dl), OR = 1.69 (1.59-1.80); HDL-cholesterol (decrease by 10 mg/dl), OR = 1.12
      (1.07-1.17); hypertension stage 1, OR = 1.35 (1.08-1.67); hypertension stage 2,
      OR = 2.01 (1.62-2.51); diabetes mellitus, OR = 1.44 (1.07-1.93). CONCLUSIONS:
      Cardiovascular risk factors as well as NKF-CKD stages 1 and 2 and proteinuria,
      the more the higher and an entirely novel finding, performing no sports,
      predicted new-onset kidney disease.

PMID- 18039643
TI  - Prescription of an intermittent haemodialysis dose using urea kinetic modelling
      is feasible in the critically ill patient.

PMID- 18039644
TI  - Tacrolimus: a new therapy for steroid-resistant nephrotic syndrome in children.
AB  - This study was conducted to evaluate the safety and efficacy of tacrolimus (TAC)
      in children with SRNS. The study group comprised of 22 consecutive children with
      steroid-resistant nephrotic syndrome (SRNS) who were studied prospectively. TAC
      was initiated with a dose of 0.10 mg/kg/day, and the dose was increased to attain
      a trough level of 5.0-10.0 g/l. These patients were treated with concomitant
      prednisone, which was subsequently tapered off and stopped. The primary outcome
      variable was the number of patients who attained a complete remission (CR) or
      partial remission (PR). The mean age of onset was 7.33 +/- 5.9 years, and there
      were 20 boys and 2 girls. Of the 22 children, 9 had minimal change disease, 11
      had focal segmental glomerulosclerosis and the other 2 had diffuse mesangial
      hypercellularity on histopathology. TAC had to be withdrawn in 3 children because
      of its side effects. Of the remaining 19 children who received adequate therapy
      and were able to achieve target levels, CR was seen in 16 (84%) children, 2
      (10.5%) attained PR and 1 was nonresponsive. The mean time to achieve remission
      was 63.2 +/- 44 days and the mean dose of TAC was 0.18 +/- 0.07 mg/kg. The mean
      urine spot protein/creatinine ratios were significantly lower (0.33 +/- 0.58 vs.
      13.5 +/- 21.9 mg/mg, p = 0.002) and the mean serum albumin levels were
      significantly higher (3.92 +/- 0.35 g/dl vs. 2.39 +/- 0.56 g/dl, p = 0.00005), as
      compared to those prior to starting TAC. The mean glomerular filtration rate
      values at the end of the study were similar to those prior to starting TAC (97.9
      +/- 21.2 ml/min/1.73 m(2) vs. 96.4 +/- 18.4 ml/min/1.73 m(2), p = 0.30). The mean
      duration of follow-up was 290 +/- 126 days. This is the largest study so far on
      the safety and efficacy of TAC therapy in SRNS. Our results suggest that TAC is
      an effective therapeutic modality for SRNS, including the subgroup of children
      who are nonresponsive to the current therapeutic modalities like cyclophosphamide
      and cyclosporine.

PMID- 18039645
TI  - Risk factors of the progression of abdominal aortic calcification in patients on
      chronic haemodialysis.

PMID- 18039647
TI  - Identifying patients with type 2 diabetes at high risk of microalbuminuria:
      results of the DEMAND (Developing Education on Microalbuminuria for Awareness of
      reNal and cardiovascular risk in Diabetes) Study.
AB  - BACKGROUND: We evaluated to what extent the presence of risk factors and their
      interactions increased the likelihood of microalbuminuria (MAU) among individuals
      with type 2 diabetes. METHODS: Fifty-five Italian diabetes outpatient clinics
      enrolled a sample of patients with type 2 diabetes, without urinary infections
      and overt diabetic nephropathy. A morning spot urine sample was collected to
      centrally determine the urinary albumin/creatinine ratio (ACR). A tree-based
      regression technique (RECPAM) and multivariate analyses were performed to
      investigate interaction between correlates of MAU. RESULTS: Of the 1841 patients
      recruited, 228 (12.4%) were excluded due to the presence of urinary infections
      and 56 (3.5%) for the presence of macroalbuminuria. Overall, the prevalence of
      MAU (ACR = 30-299 mg/g) was of 19.1%. The RECPAM algorithm led to the
      identification of seven classes showing a marked difference in the likelihood of
      MAU. Non-smoker patients with HbA1c <7% and waist circumference </=102 cm showed
      the lowest prevalence of MAU (7.5%), and represented the reference class.
      Patients with retinopathy, waist circumference >98 cm and HbA1c >8% showed the
      highest likelihood of MAU (odds ratio = 13.7; 95% confidence intervals 6.8-27.6).
      In the other classes identified, the risk of MAU ranged between 3 and 5. Age,
      systolic blood pressure, HDL cholesterol levels and diabetes treatment
      represented additional, global correlates of MAU. CONCLUSIONS: The likelihood of
      MAU is strongly related to the interaction between diabetes severity, smoking
      habits and several components of the metabolic syndrome. In particular, abdominal
      obesity, elevated blood pressure levels and low HDL cholesterol levels
      substantially increase the risk of MAU. It is of primary importance to monitor
      MAU in high-risk individuals and aggressively intervene on modifiable risk
      factors.

PMID- 18039649
TI  - Identification of two homologous genes, chlAI and chlAII, that are differentially
      involved in isocyclic ring formation of chlorophyll a in the cyanobacterium
      Synechocystis sp. PCC 6803.
AB  - The isocyclic ring (E-ring) is a common structural feature of chlorophylls. The E
      ring is formed by two structurally unrelated Mg-protoporphyrin IX monomethylester
      (MPE) cyclase systems, oxygen-dependent (AcsF), and oxygen-independent (BchE)
      systems, which involve incorporation of an oxygen atom from molecular oxygen and
      water into the C-13(1) position of MPE, respectively. Which system operates in
      cyanobacteria that can thrive in a variety of anaerobic environments remains an
      open question. The cyanobacterium Synechocystis sp. PCC 6803 has two acsF-like
      genes, sll1214 (chlA(I)) and sll1874 (chlA(II)), and three bchE-like genes,
      slr0905, sll1242, and slr0309. Five mutants lacking one of these genes were
      isolated. The DeltachlA(I) mutant failed to grow under aerobic conditions with
      anomalous accumulation of a pigment with fluorescence emission peak at 595 nm,
      which was identified 3,8-divinyl MPE by high-performance liquid chromatography
      mass spectrometry analysis. The growth defect of DeltachlA(I) was restored by the
      cultivation under oxygen-limited (micro-oxic) conditions. MPE accumulation was
      also detected in DeltachlA(II) grown under microoxic conditions, but not in any
      of the bchE mutants. The phenotype was consistent with the expression pattern of
      two chlA genes: chlA(II) was induced under micro-oxic conditions in contrast to
      the constitutive expression of chlA(I). These findings suggested that ChlA(I) is
      the sole MPE cyclase system under aerobic conditions and that the induced
      ChlA(II) operates together with ChlA(I) under micro-oxic conditions. In addition,
      the accumulation of 3,8-divinyl MPE in the DeltachlA mutants suggested that the
      reduction of 8-vinyl group occurs after the formation of E-ring in Synechocystis
      sp. PCC 6803.

PMID- 18039648
TI  - Clinical policies on the management of chronic kidney disease patients in Italy.
AB  - BACKGROUND: Recent studies have indicated that the implementation of
      international guidelines for the management of renal patients is suboptimal in
      Italy. The Italian Society of Nephrology (SIN) decided to undertake a multicentre
      study to obtain a clear picture of clinical policies on chronic kidney disease
      (CKD) in Italy. METHODS: A 76-item structured questionnaire, designed to evaluate
      the organization of clinical care, was administered to the director of each
      participating centre, within the context of a large observational trial in 100
      Italian nephrology centres, collecting information on newly diagnosed CKD
      patients (K/DOQI stage 3-5) on conservative treatment. This paper reports the
      questionnaire results related to management of anaemia and bone metabolism
      disorders; assessment of renal function; creation of a vascular access for
      dialysis and referral of patients to a nephrologist. RESULTS: Clinical policies
      at the centre level deviated from guideline recommendations in 70% (timing of
      vascular access creation) to 25% (assessment of iron deficiency) of centres.
      Assessment of renal function differed from the recommended approach in 30% of
      centres; clinical policies related to anaemia and bone disease did not coincide
      with guideline standards in 50 and 40% of centres, respectively. Directors of
      renal unit estimates indicate that the creation of a vascular access occurs very
      late in 38% of patients and that referral to a nephrologist is late in
      approximately 40% of cases. CONCLUSION: This survey in Italy highlights important
      deviations of clinical policies at the centre level from guideline
      recommendations.

PMID- 18039650
TI  - The regulated cell surface zymogen activation of the proprotein convertase PC5A
      directs the processing of its secretory substrates.
AB  - The proprotein convertases are synthesized as zymogens that acquire activity upon
      autocatalytic removal of their NH(2)-terminal prosegment. Based on the convertase
      furin, to fold properly and gain activity, the convertases PC5A, PACE4, and PC7
      are presumed to undergo two sequential prosegment cleavages in the endoplasmic
      reticulum and then in the trans-Golgi network. However, biochemical and
      immunocytochemical experiments revealed that mouse PC5A is complexed to its
      prosegment at the plasma membrane. This labeling is lost upon treatment with
      heparin and is increased by overexpressing members of the syndecan family and
      CD44, suggesting attachment of secreted PC5A-prosegment complex to heparan
      sulfate proteoglycans. Following stimulation of Y1 cells with adrenocorticotropic
      hormone or 8-bromo-cyclic AMP, the cell surface labeling of the prosegment of
      PC5A is greatly diminished, whereas the signal for mature PC5A is increased.
      Moreover, after stimulation, the protease activity of PC5A is enhanced, as
      evidenced by the cleavage of the PC5A substrates Lefty, ADAMTS-4, endothelial
      lipase, and PCSK9. Our data suggest a novel mechanism for PC5A activation and
      substrate cleavage at the cell surface, through a regulated removal of its
      prosegment. A similar mechanism may also apply to the convertase PACE4, thereby
      extending our knowledge of the molecular details of the zymogen activation and
      functions of these heparan sulfate proteoglycan-bound convertases.

PMID- 18039651
TI  - Inhibitor-complexed structures of the cytochrome bc1 from the photosynthetic
      bacterium Rhodobacter sphaeroides.
AB  - The cytochrome bc(1) complex (bc(1)) is a major contributor to the proton motive
      force across the membrane by coupling electron transfer to proton translocation.
      The crystal structures of wild type and mutant bc(1) complexes from the
      photosynthetic purple bacterium Rhodobacter sphaeroides (Rsbc(1)), stabilized
      with the quinol oxidation (Q(P)) site inhibitor stigmatellin alone or in
      combination with the quinone reduction (Q(N)) site inhibitor antimycin, were
      determined. The high quality electron density permitted assignments of a new
      metal-binding site to the cytochrome c(1) subunit and a number of lipid and
      detergent molecules. Structural differences between Rsbc(1) and its mitochondrial
      counterparts are mostly extra membranous and provide a basis for understanding
      the function of the predominantly longer sequences in the bacterial subunits.
      Functional implications for the bc(1) complex are derived from analyses of 10
      independent molecules in various crystal forms and from comparisons with
      mitochondrial complexes.

PMID- 18039652
TI  - Complex I is the major site of mitochondrial superoxide production by paraquat.
AB  - Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride) is widely used as a redox
      cycler to stimulate superoxide production in organisms, cells, and mitochondria.
      This superoxide production causes extensive mitochondrial oxidative damage,
      however, there is considerable uncertainty over the mitochondrial sites of
      paraquat reduction and superoxide formation. Here we show that in yeast and
      mammalian mitochondria, superoxide production by paraquat occurs in the
      mitochondrial matrix, as inferred from manganese superoxide dismutase-sensitive
      mitochondrial DNA damage, as well as from superoxide assays in isolated
      mitochondria, which were unaffected by exogenous superoxide dismutase. This
      paraquat-induced superoxide production in the mitochondrial matrix required a
      membrane potential that was essential for paraquat uptake into mitochondria. This
      uptake was of the paraquat dication, not the radical monocation, and was carrier
      mediated. Experiments with disrupted mitochondria showed that once in the matrix
      paraquat was principally reduced by complex I (mammals) or by NADPH
      dehydrogenases (yeast) to form the paraquat radical cation that then reacted with
      oxygen to form superoxide. Together this membrane potential-dependent uptake
      across the mitochondrial inner membrane and the subsequent rapid reduction to the
      paraquat radical cation explain the toxicity of paraquat to mitochondria.

PMID- 18039653
TI  - Autophagy is involved in nutritional stress response and differentiation in
      Trypanosoma cruzi.
AB  - Autophagy is the major mechanism used by eukaryotic cells to degrade and recycle
      proteins and organelles. Bioinformatics analysis of the genome of the protozoan
      parasite Trypanosoma cruzi revealed the presence of all components of the Atg8
      conjugation system, whereas Atg12, Atg5, and Atg10 as the major components of the
      Atg12 pathway could not be identified. The two TcATG4 (autophagin) homologs
      present in the genome were found to correctly process the two ATG8 homologs after
      the conserved Gly residue. Functional studies revealed that both ATG4 homologues
      but only one T. cruzi ATG8 homolog (TcATG8.1) complemented yeast deletion
      strains. During starvation of the parasite, TcAtg8.1, but not TcAtg8.2, was found
      by immunofluorescence to be located in autophagosome-like vesicles. This confirms
      its function as an Atg8/LC3 homolog and its potential to be used as an
      autophagosomal marker. Most importantly, autophagy is involved in differentiation
      between developmental stages of T. cruzi, a process that is essential for
      parasite maintenance and survival. These findings suggest that the autophagy
      pathway could represent a target for a novel chemotherapeutic strategy against
      Chagas disease.

PMID- 18039654
TI  - The pentatricopeptide repeats present in Pet309 are necessary for translation but
      not for stability of the mitochondrial COX1 mRNA in yeast.
AB  - Pet309 is a protein essential for respiratory growth. It is involved in
      translation of the yeast mitochondrial COX1 gene, which encodes subunit I of the
      cytochrome c oxidase. Pet309 is also involved in stabilization of the COX1 mRNA.
      Mutations in a similar human protein, Lrp130, are associated with Leigh syndrome,
      where cytochrome c oxidase activity is affected. The sequence of Pet309 reveals
      the presence of at least seven pentatricopeptide repeats (PPRs) located in tandem
      in the central portion of the protein. Proteins containing PPR motifs are present
      in mitochondria and chloroplasts and are in general involved in RNA metabolism.
      Despite the increasing number of proteins from this family found to play
      essential roles in mitochondria and chloroplasts, little is understood about the
      mechanism of action of the PPR domains present in these proteins. In a series of
      in vivo analyses we constructed a pet309 mutant lacking the PPR motifs. Although
      the stability of the COX1 mRNA was not affected, synthesis of Cox1 was abolished.
      The deletion of one PPR motif at a time showed that all the PPR motifs are
      required for COX1 mRNA translation and respiratory growth. Mutations of basic
      residues in PPR3 caused reduced respiratory growth. According to a molecular
      model, these residues are facing a central cavity that could be involved in mRNA
      binding activity, forming a possible path for this molecule on Pet309. Our
      results show that the RNA metabolism function of Pet309 is found in at least two
      separate domains of the protein.

PMID- 18039655
TI  - Deletion of the selenocysteine tRNA gene in macrophages and liver results in
      compensatory gene induction of cytoprotective enzymes by Nrf2.
AB  - The selenocysteine tRNA (tRNA(Sec)) molecule is the sight of synthesis for the
      amino acid selenocysteine and the adaptor for its translational insertion into
      selenoprotein enzymes, the majority of which contribute to cellular redox
      homeostasis. To examine the consequences of selenoprotein depletion on the
      oxidative environment of the cell, we generated a conditional knock-out mouse for
      the tRNA(Sec) gene (Trsp). Deletion of Trsp in either macrophages or liver
      elevated oxidative stress and activated the transcriptional induction of
      cytoprotective antioxidant and detoxification enzyme genes, including glutathione
      S-transferase P1 and NAD(P)H:quinone oxidoreductase 1, and other well known
      target genes of the transcription factor Nrf2 (NF-E2-related factor 2).
      Simultaneous disruption of Trsp and Nrf2 severely compromised the cytoprotective
      response. Double knock-out macrophages displayed reduced viability, elevated
      oxidative stress, and increased susceptible to hydrogen peroxide treatment
      compared with deletion of either gene alone. Mice carrying a liver-specific
      deletion of Trsp on an Nrf2-null background experienced hepatocellular apoptosis
      and displayed a severely reduced survival rate compared with loss of Trsp alone.
      Our results thus demonstrate that reduced selenoprotein activity is
      counterbalanced by an Nrf2-mediated cytoprotective response, which is essential
      for maintaining cellular redox homeostasis and viability.

PMID- 18039656
TI  - Formation of a major histocompatibility complex class I tapasin disulfide
      indicates a change in spatial organization of the peptide-loading complex during
      assembly.
AB  - The assembly and peptide loading of major histocompatibility complex Class I
      molecules within the endoplasmic reticulum are essential for antigen presentation
      at the cell surface and are facilitated by the peptide-loading complex. The
      formation of a mixed disulfide between the heavy chain of Class I and components
      of the loading complex (ERp57, protein disulfide isomerase, and tapasin) suggests
      that these molecules are involved in the redox regulation of components during
      assembly and peptide loading. We demonstrate here that a disulfide formed between
      heavy chain and tapasin can occur between cysteine residues located in the
      cytosolic regions of these proteins following translation of heavy chain in an in
      vitro translation system. The formation of this disulfide occurs after assembly
      into the loading complex and is coincident with the stabilization of the alpha2
      disulfide bond within the peptide binding grove. A ternary complex between heavy
      chain, ERp57, and tapasin was observed and shown to be stabilized by a disulfide
      between both tapasinheavy chain and tapasin-ERp57. No disulfides were observed
      between ERp57 and heavy chain within the loading complex. The results provide a
      detailed evaluation of the various transient disulfides formed within the peptide
      loading complex during biosynthesis. In addition, the absence of the disulfide
      between tapasin and heavy chain in TAP-deficient cells indicates that a change in
      the spatial organization of tapasin and heavy chain occurs following assembly
      into the loading complex.

PMID- 18039657
TI  - Mutational activation of ErbB2 reveals a new protein kinase autoinhibition
      mechanism.
AB  - Autoinhibition plays a key role in the control of protein kinase activity. ErbB2
      is a unique receptor-tyrosine kinase that does not bind ligand but possesses an
      extracellular domain poised to engage other ErbBs. Little is known about the
      molecular mechanism for ErbB2 catalytic regulation. Here we show that ErbB2
      kinase is strongly autoinhibited, and a loop connecting the alphaC helix and
      beta4 sheet within the kinase domain plays a major role in the control of kinase
      activity. Mutations of two Gly residues at positions 776 and 778 in this loop
      dramatically increase ErbB2 catalytic activity. Kinetic analysis demonstrates
      that mutational activation is due to approximately 10- and approximately 7-fold
      increases in ATP binding affinity and turnover number, respectively. Expression
      of the activated ErbB2 mutants in cells resulted in elevated ligand-independent
      ErbB2 autophosphorylation, ErbB3 phosphorylation, and stimulation of mitogen
      activated protein kinase. Molecular modeling suggests that the ErbB2 kinase
      domain is stabilized in an inactive state via a hydrophobic interaction between
      the alphaC-beta4 and activation loops. Importantly, many ErbB2 human cancer
      mutations have been identified in the alphaC-beta4 loop, including the activating
      G776S mutation studied here. Our findings reveal a new kinase regulatory
      mechanism in which the alphaC-beta4 loop functions as an intramolecular switch
      that controls ErbB2 activity and suggests that loss of alphaC-beta4 loop-mediated
      autoinhibition is involved in oncogenic activation of ErbB2.

PMID- 18039658
TI  - The proprotein convertase PCSK9 induces the degradation of low density
      lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2.
AB  - The proprotein convertase PCSK9 gene is the third locus implicated in familial
      hypercholesterolemia, emphasizing its role in cardiovascular diseases. Loss of
      function mutations and gene disruption of PCSK9 resulted in a higher clearance of
      plasma low density lipoprotein cholesterol, likely due to a reduced degradation
      of the liver low density lipoprotein receptor (LDLR). In this study, we show that
      two of the closest family members to LDLR are also PCSK9 targets. These include
      the very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2
      (ApoER2) implicated in neuronal development and lipid metabolism. Our results
      show that wild type PCSK9 and more so its natural gain of function mutant D374Y
      can efficiently degrade the LDLR, VLDLR, and ApoER2 either following cellular co
      expression or re-internalization of secreted human PCSK9. Such PCSK9-induced
      degradation does not require its catalytic activity. Membrane-bound PCSK9
      chimeras enhanced the intracellular targeting of PCSK9 to late
      endosomes/lysosomes and resulted in a much more efficient degradation of the
      three receptors. We also demonstrate that the activity of PCSK9 and its binding
      affinity on VLDLR and ApoER2 does not depend on the presence of LDLR. Finally, in
      situ hybridization show close localization of PCSK9 mRNA expression to that of
      VLDLR in mouse postnatal day 1 cerebellum. Thus, this study demonstrates a more
      general effect of PCSK9 on the degradation of the LDLR family that emphasizes its
      major role in cholesterol and lipid homeostasis as well as brain development.

PMID- 18039659
TI  - Structure and function of the smallest vertebrate telomerase RNA from teleost
      fish.
AB  - Telomerase extends chromosome ends by copying a short template sequence within
      its intrinsic RNA component. Telomerase RNA (TR) from different groups of species
      varies dramatically in sequence and size. We report here the bioinformatic
      identification, secondary structure comparison, and functional analysis of the
      smallest known vertebrate TRs from five teleost fishes. The teleost TRs (312-348
      nucleotides) are significantly smaller than the cartilaginous fish TRs (478-559
      nucleotides) and tetrapod TRs. This remarkable length reduction of teleost fish
      TRs correlates positively with the genome size, reflecting an unusual structural
      plasticity of TR during evolution. The teleost TR consists of a compact three
      domain structure, lacking most of the sequences in regions that are variable in
      other vertebrate TR structures. The medaka and fugu TRs, when assembled with
      their telomerase reverse transcriptase (TERT) protein counterparts, reconstituted
      active and processive telomerase enzymes. Titration analysis of individual RNA
      domains suggests that the efficient assembly of the telomerase complex is
      influenced more by the telomerase reverse transcriptase (TERT) binding of the CR4
      CR5 domain than the pseudoknot domain of TR. The remarkably small teleost fish TR
      further expands our understanding about the evolutionary divergence of vertebrate
      TR.

PMID- 18039660
TI  - Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows
      for dissociation of multiple signaling pathways for phagocytosis of apoptotic
      cells and down-modulation of lipopolysaccharide-inducible NF-kappaB
      transcriptional activation.
AB  - Efficient clearance of apoptotic cells is essential for tissue homeostasis,
      allowing for cellular turnover without inflammatory consequences. The Mer (Nyk
      and c-Eyk) receptor tyrosine kinase (Mertk) is involved in two aspects of
      apoptotic cell clearance by acting as a receptor for Gas6, a gamma-carboxylated
      phosphatidylserine-binding protein that bridges apoptotic and viable cells.
      First, Mertk acts in a bona fide engulfment pathway in concert with alphavbeta5
      integrin by regulating cytoskeletal assemblages, and second, it acts as a
      negative regulator for inflammation by down-modulating pro-inflammatory signals
      mediated from bacterial lipopolysaccharide-Toll-like receptor 4 (TLR4) signaling,
      and hence recapitulating anti-inflammatory immune modulation by apoptotic cells.
      Here we describe Mertk post-receptor events that govern phagocytosis and
      cytoskeletal signaling are principally mediated by autophosphorylation site Tyr
      867. Using the Mertk Y867F mutant and pharmacological inhibitors, we show that
      Tyr-867 is required for phosphatidylinositol 3-kinase and phospholipase Cgamma2
      activation; their activation in turn elicits protein kinase C-dependent signals
      that act on the actin cytoskeleton. Although Mertk(Y867F) blocked the tyrosine
      phosphorylation of FAK on Tyr-861 and p130(cas) and also abrogated the
      phagocytosis of apoptotic cells, this mutant did not suppress lipopolysaccharide
      inducible NF-kappaB transcription, nor was NF-kappaB activation dependent on the
      protein kinase C inhibitor, calphostin C. Finally, unlike the cytoskeletal events
      associated with Tyr-867 autophosphorylation, the trans-inhibition of NF-kappaB
      occurred in a postnuclear-dependent fashion independent of cytosolic IkappaB
      phosphorylation and p65/RelA sequestration. Taken together, these data suggest
      that Mertk has distinct and separable effects for phagocytosis and for resolving
      inflammation, providing a molecular rationale for how immune licensing and
      inflammation can be dissociated from phagocytosis in a single phagocytic
      receptor.

PMID- 18039661
TI  - Reversible tyrosine protein phosphorylation regulates large conductance voltage-
      and calcium-activated potassium channels via cortactin.
AB  - Large conductance calcium- and voltage-activated potassium (BK) channels assemble
      as macromolecular signaling complexes and are potently regulated by reversible
      protein phosphorylation. However, although numerous studies have revealed
      regulation of BK channels through changes in direct phosphorylation of the pore
      forming alpha-subunits the functional role of changes in phosphorylation of
      defined adapter/signaling proteins within the complex on channel function are
      essentially not known. Here, we demonstrate that mammalian BK channels are
      potently regulated by endogenous protein-tyrosine kinase and protein-tyrosine
      phosphatase activity closely associated with the channel. BK channel regulation
      was not dependent upon direct phosphorylation of the BK alpha-subunit, rather
      channel function was controlled by the tyrosine phosphorylation status of the
      adapter protein cortactin that assembles directly with the BK channel. Our data
      thus reveal a novel mode for BK channel regulation by reversible tyrosine
      phosphorylation and strongly support the hypothesis that phosphorylation
      dependent regulation of accessory proteins within the BK channel signaling
      complex represents an important target for control of BK channel function.

PMID- 18039662
TI  - Cyclic nucleotide-dependent protein kinases inhibit binding of 14-3-3 to the
      GTPase-activating protein Rap1GAP2 in platelets.
AB  - GTPase-activating proteins are required to terminate signaling by Rap1, a small
      guanine nucleotide-binding protein that controls integrin activity and cell
      adhesion. Recently, we identified Rap1GAP2, a GTPase-activating protein of Rap1
      in platelets. Here we show that 14-3-3 proteins interact with phosphorylated
      serine 9 at the N terminus of Rap1GAP2. Platelet activation by ADP and thrombin
      enhances serine 9 phosphorylation and increases 14-3-3 binding to endogenous
      Rap1GAP2. Conversely, inhibition of platelets by endothelium-derived factors
      nitric oxide and prostacyclin disrupts 14-3-3 binding. These effects are mediated
      by cGMP- and cAMP-dependent protein kinases that phosphorylate Rap1GAP2 at serine
      7, adjacent to the 14-3-3 binding site. 14-3-3 binding does not change the GTPase
      activating function of Rap1GAP2 in vitro. However, 14-3-3 binding attenuates
      Rap1GAP2 mediated inhibition of cell adhesion. Our findings define a novel
      crossover point of activatory and inhibitory signaling pathways in platelets.

PMID- 18039663
TI  - BAX inhibitor-1 modulates endoplasmic reticulum stress-mediated programmed cell
      death in Arabidopsis.
AB  - The components and pathways that regulate programmed cell death (PCD) in plants
      remain poorly understood. Here we describe the impact of drug-induced endoplasmic
      reticulum (ER) stress on Arabidopsis seedlings and present evidence for the role
      of Arabidopsis BAX inhibitor-1 (AtBI1) as a modulator of ER stress-mediated PCD.
      We found that treatment of Arabidopsis seedlings with tunicamycin (TM), an
      inhibitor of N-linked glycosylation and an inducer of ER stress by triggering
      accumulation of unfolded proteins in the ER, results in strong inhibition of root
      growth and loss of survival accompanied by typical hallmarks of PCD such as
      accumulation of H(2)O(2), chromatin condensation, and oligonucleosomal
      fragmentation of nuclear DNA. These phenotypes are alleviated by co-treatment
      with either of two different chemical chaperones, sodium 4-phenylbutyrate and
      tauroursodeoxycholic acid, both with chaperone properties that can reduce the
      load of misfolded protein in the ER. Expression of AtBI1 mRNA and its promoter
      activity are increased dramatically prior to initiation of TM-induced PCD.
      Compared with wild-type plants, two AtBI1 mutants (atbi1-1 and atbi1-2) exhibit
      hypersensitivity to TM with accelerated PCD progression. Conversely,
      overexpressing AtBI1 markedly reduces the sensitivity of Arabidopsis seedlings to
      TM. However, alterations in AtBI1 gene expression levels do not cause a
      significant effect on the expression patterns of typical ER stress-inducible
      genes (AtBip2, AtPDI, AtCRT1, and AtCNX1). We propose that AtBI1 plays a pivotal
      role as a highly conserved survival factor during ER stress that acts in parallel
      to the unfolded protein response pathway.

PMID- 18039664
TI  - In vitro reconstitution of plant Atg8 and Atg12 conjugation systems essential for
      autophagy.
AB  - Genetic and biochemical analyses using yeast Saccharomyces cerevisiae showed that
      two ubiquitin-like conjugation systems, the Atg8 and Atg12 systems, exist and
      play essential roles in autophagy, the bulk degradation system conserved in yeast
      and mammals. These conjugation systems are also conserved in Arabidopsis
      thaliana; however, further detailed study of plant ATG (autophagy-related)
      conjugation systems in relation to those in yeast and mammals is needed. Here, we
      describe the in vitro reconstitution of Arabidopsis thaliana ATG8 and ATG12
      (AtATG8 and AtATG12) conjugation systems using purified recombinant proteins.
      AtATG12b was conjugated to AtATG5 in a manner dependent on AtATG7, AtATG10, and
      ATP, whereas AtATG8a was conjugated to phosphatidylethanolamine (PE) in a manner
      dependent on AtATG7, AtATG3, and ATP. Other AtATG8 homologs (AtATG8b-8i) were
      similarly conjugated to PE. The AtATG8 conjugates were deconjugated by AtATG4a
      and AtATG4b. These results support the hypothesis that the ATG conjugation
      systems in Arabidopsis are very similar to those in yeast and mammals.
      Intriguingly, in vitro analyses showed that AtATG12-AtATG5 conjugates accelerated
      the formation of AtATG8-PE, whereas AtATG3 inhibited the formation of AtATG12
      AtATG5 conjugates. The in vitro conjugation systems reported here will afford a
      tool with which to investigate the cross-talk mechanism between two conjugation
      systems.

PMID- 18039666
TI  - Characterization of a short isoform of human Tgs1 hypermethylase associating with
      small nucleolar ribonucleoprotein core proteins and produced by limited
      proteolytic processing.
AB  - Tgs1 is the hypermethylase responsible for m(3)G cap formation of U small nuclear
      RNAs (U snRNAs) and small nucleolar RNAs (snoRNAs). In vertebrates,
      hypermethylation of snRNAs occurs in the cytoplasm, whereas this process takes
      place in the nucleus for snoRNAs. Accordingly, the hypermethylase is found in
      both compartments with a diffuse localization in the cytoplasm and a
      concentration in Cajal bodies in the nucleoplasm. In this study, we report that
      the Tgs1 hypermethylase exists as two species, a full-length cytoplasmic isoform
      and a shorter nuclear isoform of 65-70 kDa. The short isoform exhibits
      methyltransferase activity and associates with components of box C/D and H/ACA
      snoRNPs, pointing to a role of this isoform in hypermethylation of snoRNAs. We
      also show that production of the short Tgs1 isoform is inhibited by MG132,
      suggesting that it results from proteasomal limited processing of the full-length
      Tgs1 protein. Together, our results suggest that proteasome maturation
      constitutes a mechanism regulating Tgs1 function by generating Tgs1 species with
      different substrate specificities, subcellular localizations, and functions.

PMID- 18039665
TI  - The lack of binding of VEK-30, an internal peptide from the group A streptococcal
      M-like protein, PAM, to murine plasminogen is due to two amino acid replacements
      in the plasminogen kringle-2 domain.
AB  - VEK-30, a 30-amino acid internal peptide present within a streptococcal M-like
      plasminogen (Pg)-binding protein (PAM) from Gram-positive group-A streptococci
      (GAS), represents an epitope within PAM that shows high affinity for the lysine
      binding site (LBS) of the kringle-2 (K2) domain of human (h)Pg. VEK-30 does not
      interact with this same region of mouse (m)Pg, despite the high conservation of
      the mK2- and hK2-LBS. To identify the molecular basis for the species specificity
      of this interaction, hPg and mPg variants were generated, including an hPg
      chimera with the mK2 sequence and an mPg chimera containing the hK2 sequence. The
      binding of synthetic VEK-30 to these variants was studied by surface plasmon
      resonance. The data revealed that, in otherwise intact Pg, the species
      specificity of VEK-30 binding in these two cases is entirely dictated by two K2
      residues that are different between hPg and mPg, namely, Arg-220 of hPg, which is
      a Gly in mPg, and Leu-222 of hPg, which is a Pro in mPg, neither of which are
      members of the canonical K2-LBS. Neither the activation of hPg, nor the enzymatic
      activity of its activated product, plasmin (hPm), are compromised by replacing
      these two amino acids by their murine counterparts. It is also demonstrated that
      hPg is more susceptible to activation to hPm after complexation with VEK-30 and
      that this property is greatly reduced as a result of the R220G and L222P
      replacements in hPg. These mechanisms for accumulation of protease activity on
      GAS likely contribute to the virulence of PAM(+)-GAS strains and identify targets
      for new therapeutic interventions.

PMID- 18039667
TI  - PIKfyve negatively regulates exocytosis in neurosecretory cells.
AB  - Regulated secretion depends upon a highly coordinated series of protein-protein
      and protein-lipid interactions. Two phosphoinositides, phosphatidylinositol 4,5
      bisphosphate and phosphatidylinositol 3-phosphate, are important for the ATP
      dependent priming of the secretory apparatus prior to Ca(2+)-dependent
      exocytosis. Mechanisms that control phosphoinositide levels are likely to play an
      important role in priming fine tuning. Here we have investigated the involvement
      of PIKfyve, a phosphoinositide 5-kinase that can phosphorylate
      phosphatidylinositol 3-phosphate to produce phosphatidylinositol 3,5-bisphosphate
      on large dense core vesicle exocytosis from neuroendocrine cells. PIKfyve
      localizes to a subpopulation of secretory granules in chromaffin and PC12 cells.
      Nicotine stimulation promoted recruitment of PIKfyve-EGFP onto secretory vesicles
      in PC12 cells. YM-201636, a selective inhibitor of PIKfyve activity, and PIKfyve
      knockdown by small interfering RNA potentiated secretory granule exocytosis.
      Overexpression of PIKfyve or its yeast orthologue Fab1p inhibited regulated
      secretion in PC12 cells, whereas a catalytically inactive PIKfyve mutant had no
      effect. These results demonstrate a novel inhibitory role for PIKfyve catalytic
      activity in regulated secretion and provide further evidence for a fine tuning of
      exocytosis by 3-phosphorylated phosphoinositides.

PMID- 18039668
TI  - Ligand dynamics and early signaling events in the heme domain of the sensor
      protein Dos from Escherichia coli.
AB  - In the heme-based sensor Dos from Escherichia coli, the ferrous heme is
      coordinated by His-77 and Met-95. The latter residue is replaced upon oxygen
      binding or oxidation of the heme. Here we investigate the early signaling
      processes upon dissociation of the distal ligand using ultrafast spectroscopy and
      site-directed mutagenesis. Geminate CO rebinding to the heme domain DosH appears
      insensitive to replacement of Met-95, in agreement with the notion that this
      residue is oriented out of the heme pocket in the presence of external ligands. A
      uniquely slow 35-ps phase in rebinding of the flexible methionine side chain
      after dissociation from ferrous DosH is completely abolished in rebinding of the
      more rigid histidine side chain in the M95H mutant protein, where only the 7-ps
      phase, common to all 6-coordinate heme proteins, is observed. Temperature
      dependence studies indicate that all rebinding of internal and external ligands
      is essentially barrierless, but that CfigsO escape from the heme pocket is an
      activated process. Solvent viscosity studies combined with molecular dynamics
      simulations show that there are two configurations in the ferrous 6-coordinate
      protein, involving two isomers of the Met-95 side chain, of which the structural
      changes extend to the solvent-exposed backbone, which is part of the flexible FG
      loop. One of these configurations has considerable motional freedom in the Met-95
      dissociated state. We suggest that this configuration corresponds to an early
      signaling intermediate state, is responsible for the slow rebinding, and allows
      small ligands in the protein to efficiently compete for binding with the heme.

PMID- 18039669
TI  - Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase
      and mammalian target of rapamycin-dependent mechanism.
AB  - Leptin is an adipocyte-derived hormone/cytokine that links nutritional status
      with neuroendocrine and immune functions. Lipid bodies (lipid droplets) are
      emerging as dynamic organelles with roles in lipid metabolism and inflammation.
      Here we investigated the roles of leptin in signaling pathways involved in
      cytoplasmic lipid body biogenesis and leukotriene B(4) synthesis in macrophages.
      Our results demonstrated that leptin directly activated macrophages and induced
      the formation of adipose differentiation-related protein-enriched lipid bodies.
      Newly formed lipid bodies were sites of 5-lipoxygenase localization and
      correlated with an enhanced capacity of leukotriene B(4) production. We
      demonstrated that leptin-induced macrophage activation was dependent on
      phosphatidylinositol 3-kinase (PI3K) activity, since the lipid body formation was
      inhibited by LY294002 and was absent in the PI3K knock-out mice. Leptin induces
      phosphorylation of p70(S6K) and 4EBP1 key downstream signaling intermediates of
      the mammalian target of rapamycin (mTOR) pathway in a rapamycin-sensitive
      mechanism. The mTOR inhibitor, rapamycin, inhibited leptin-induced lipid body
      formation, both in vivo and in vitro. In addition, rapamycin inhibited leptin
      induced adipose differentiation-related protein accumulation in macrophages and
      lipid body-dependent leukotriene synthesis, demonstrating a key role for mTOR in
      lipid body biogenesis and function. Our results establish PI3K/mTOR as an
      important signaling pathway for leptin-induced cytoplasmic lipid body biogenesis
      and adipose differentiation-related protein accumulation. Furthermore, we
      demonstrate a previously unrecognized link between intracellular (mTOR) and
      systemic (leptin) nutrient sensors in macrophage lipid metabolism. Leptin-induced
      increased formation of cytoplasmic lipid bodies and enhanced inflammatory
      mediator production in macrophages may have implications for obesity-related
      cardiovascular diseases.

PMID- 18039670
TI  - Postnatal requirement of the epithelial sodium channel for maintenance of
      epidermal barrier function.
AB  - In skin, the physiological consequence of an epithelial sodium channel (ENaC)
      deficiency is not obvious directly at birth. Nevertheless, within hours after
      birth, mice deficient for the alpha-subunit of the highly amiloride-sensitive
      epithelial sodium channel (alphaENaC/Scnn1a) suffer from a significant increased
      dehydration. This is characterized by a loss of body weight (by 6% in 6 h) and an
      increased transepidermal water loss, which is accompanied by a higher skin
      surface pH in 1-day-old pups. Although early and late differentiation markers, as
      well as tight junction protein distribution and function, seem unaffected,
      deficiency of alphaENaC severely disturbs the stratum corneum lipid composition
      with decreased ceramide and cholesterol levels, and increased pro-barrier lipids,
      whereas covalently bound lipids are drastically reduced. Ultrastructural analysis
      revealed morphological changes in the formation of intercellular lamellar lipids
      and the lamellar body secretion. Extracellular formation of the lamellar lipids
      proved to be abnormal in the knockouts. In conclusion, ENaC deficiency results in
      progressive dehydration and, consequently, weight loss due to severe impairment
      of lipid formation and secretion. Our data demonstrate that ENaC expression is
      required for the postnatal maintenance of the epidermal barrier function but not
      for its generation.

PMID- 18039671
TI  - Matrix metalloproteinase 13 (MMP13) and tissue inhibitor of matrix
      metalloproteinase 1 (TIMP1), regulated by the MAPK pathway, are both necessary
      for Madin-Darby canine kidney tubulogenesis.
AB  - A classic model of tubulogenesis utilizes Madin-Darby canine kidney (MDCK) cells.
      MDCK cells form monoclonal cysts in three-dimensional collagen and tubulate in
      response to hepatocyte growth factor, which activates multiple signaling
      pathways, including the mitogen-activated protein kinase (MAPK) pathway. It was
      shown previously that MAPK activation is necessary and sufficient to induce the
      first stage of tubulogenesis, the partial epithelial to mesenchymal transition (p
      EMT), whereas matrix metalloproteinases (MMPs) are necessary for the second
      redifferentiation stage. To identify specific MMP genes, their regulators, tissue
      inhibitors of matrix metalloproteinases (TIMPs), and the molecular pathways by
      which they are activated, we used two distinct MAPK inhibitors and a technique we
      have termed subtraction pathway microarray analysis. Of the 19 MMPs and 3 TIMPs
      present on the Canine Genome 2.0 Array, MMP13 and TIMP1 were up-regulated 198-
      and 169-fold, respectively, via the MAPK pathway. This was confirmed by two
      dimensional and three-dimensional real time PCR, as well as in MDCK cells
      inducible for the MAPK gene Raf. Knockdown of MMP13 using short hairpin RNA
      prevented progression past the initial phase of p-EMT. Knockdown of TIMP1
      prevented normal cystogenesis, although the initial phase of p-EMT did
      occasionally occur. The MMP13 knockdown phenotype is likely because of decreased
      collagenase activity, whereas the TIMP1 knockdown phenotype appears due to
      increased apoptosis. These data suggest a model, which may also be important for
      development of other branched organs, whereby the MAPK pathway controls both MDCK
      p-EMT and redifferentiation, in part by activating MMP13 and TIMP1.

PMID- 18039672
TI  - RhoBTB2 (DBC2) is a mitotic E2F1 target gene with a novel role in apoptosis.
AB  - We have identified the RhoBTB2 putative tumor suppressor gene as a direct target
      of the E2F1 transcription factor. Overexpression of E2F1 led to up-regulation of
      RhoBTB2 at the level of mRNA and protein. This also occurred during the induction
      of E2F1 activity in the presence of cycloheximide, thus indicating that RhoBTB2
      is a direct target. RNAi-mediated knockdown of E2F1 resulted in decreased RhoBTB2
      protein expression, demonstrating that RhoBTB2 is a physiological target of E2F1.
      Because E2F1 primarily serves to transcribe genes involved in cell cycle
      progression and apoptosis, we explored whether RhoBTB2 played roles in either of
      these processes. We found RhoBTB2 expression highly up-regulated during mitosis,
      which was partially dependent on the presence of E2F1. Furthermore,
      overexpression of RhoBTB2 induced a short term increase in cell cycle progression
      and proliferation, while long term expression had a negative effect on these
      processes. We similarly found RhoBTB2 up-regulated during drug-induced apoptosis,
      with this being primarily dependent on E2F1. Finally, we observed that knockdown
      of RhoBTB2 levels via siRNA delayed the onset of drug-induced apoptosis.
      Collectively, we describe RhoBTB2 as a novel direct target of E2F1 with roles in
      cell cycle and apoptosis.

PMID- 18039673
TI  - Correlation between the SERT binding densities in hypothalamus and amygdala in
      Cloninger type 1 and 2 alcoholics.
AB  - Serotonin plays a role in the regulation of emotional states in amygdala which in
      turn affect the function of hypothalamus. The physiological effects of emotions
      are mediated to autonomic nervous system by the hypothalamus, also innervated by
      the serotonergic Raphe nuclei. AIMS: We evaluated the putative alterations of the
      serotonin transporter (SERT) density in the paraventricular nucleus (PVN) of
      hypothalamus of Cloninger type 1 and 2 (early onset, anti-social) alcoholics and
      controls. METHODS: The study was performed by human whole-hemisphere auto
      radiography with [3H]citalopram. RESULTS: Substantially sparser SERT density (
      26%) with a moderate effect size (0.53) was observed in the hypothalamus of
      alcoholic subjects in relation to non-alcoholic comparison subjects, although the
      result failed to reach statistical significance. In type 2 alcoholics, there was
      a trend towards decreased SERT binding with large effect size (0.88), and no
      correlation between the SERT binding and the age at the time of death. There was
      a strong positive correlation between the SERT binding in amygdala and in PVN in
      type 2 alcoholics (P = 0.001), and negative correlation in type 1 alcoholics (P =
      0.05), and no correlation in the control subjects. The difference between the
      groups was significant (chi2 = 16.75, P = 0.0002). CONCLUSIONS: Taken together,
      these preliminary results support the hypothesis that the serotonergic regulation
      in the hypothalamus and amygdala are defected especially in type 2 alcoholics.

PMID- 18039674
TI  - Alcohol consumption, %CDT, GGT and blood pressure change during alcohol
      treatment.
AB  - AIMS: Blood pressure (BP) changes in alcohol-dependent individuals during a 12
      week alcohol relapse prevention study were examined in light of drinking status
      and biomarkers of alcohol consumption [carbohydrate-deficient transferrin (%CDT)
      and gamma-glutamyl transpeptidase (GGT)]. METHODS: Of 160 randomized alcoholic
      individuals, 120 who had hypertension and in whom daily drinking data was
      available, at 6 and 12 weeks of treatment were included. The impact of alcohol
      consumption on change in systolic BP (SBP) and diastolic BP (DBP) was examined.
      Further analysis determined the relationship between BP and alcohol-use
      biomarkers. RESULTS: A significant effect of complete abstinence on both SBP (-10
      mmHg; P = 0.003) and DBP (-7 mmHg; P = 0.001) when compared to any drinking (SBP
      and DBP = -1 mmHg) was observed. At week 12, participants with a positive %CDT (>
      or =2.6) had 7 mmHg greater SBP (P = 0.01) and DBP (P < 0.001) than those with
      negative %CDT. Participants with positive GGT (> or =50 IU) had 10 mmHg greater
      SBP (P = 0.12) and 9 mmHg greater DBP (P = 0.03) than those with negative GGT.
      The percent change in SBP was correlated with percent change in %CDT (P = 0.003)
      but not GGT (P = ns). The percent change in DBP was correlated with both percent
      change in %CDT (P < 0.0001) and GGT (P = 0.03). CONCLUSIONS: Abstinence from
      alcohol significantly decreased the BP and a positive relationship between BP and
      both alcohol-use biomarkers was illustrated. Since %CDT is more specific than GGT
      for heavy alcohol consumption, clinicians may monitor the role of alcohol in
      hypertension using %CDT as a supplemental aid, providing an objective assessment
      of drinking to influence BP treatment decisions.

PMID- 18039675
TI  - Dose-response relation between volume of drinking and alcohol-related diseases in
      male general hospital inpatients.
AB  - AIMS: Previous studies investigating dose-response relations between volume of
      drinking and diseases have focused on single diseases only. Until now, the
      relation between the drinking volume and the risk of having any alcohol
      attributable disease is largely unknown. The aim of the present study is to
      investigate to what extent is the risk of diseases with different alcohol
      attributable fractions (AAFs) predicted by daily alcohol consumption (> 120 g, 61
      120 g vs 31-60 g). METHODS: The sample consisted of 805 inpatients classified as
      at-risk drinking, aged 18-64 years hailing from four general hospitals in North
      eastern Germany. Inpatients were classified into three groups (AAF = 1, AAF < 1,
      AAF = 0). Group differences regarding alcohol-related variables, smoking, and
      demographics were analysed. A multinomial logistic regression analysis was
      conducted to predict the risk of diseases with AAF = 1 and AAF < 1. RESULTS: In
      our sample, 26.6% of the inpatients showed a disease with AAF = 1, while 20.2%
      had a disease with AAF < 1. Inpatients consuming > 120 g, and inpatients
      consuming 61-120 g revealed significantly higher odds for diseases with AAF = 1
      compared to inpatients consuming 31-60 g (OR = 6.30, CI = 3.55-11.26; OR = 2.91,
      CI = 1.64-5.13). Regarding diseases with AAF < 1, inpatients consuming > 120 g
      revealed significantly higher odds compared to the inpatients consuming 31-60 g
      (OR = 1.97, CI = 1.15-3.37). CONCLUSION: A dose-response relation between the
      level of the drinking volume and the risk of diseases with AAF = 1 was found in
      this sample of inpatients from the general hospitals.

PMID- 18039676
TI  - Obesity and related behaviors among adolescent school boys in Abha City,
      Southwestern Saudi Arabia.
AB  - Using stratified sampling technique 2696 adolescent school boys (aged 11-19
      years) in Abha City, Southwestern Saudi Arabia were interviewed and examined for
      weight and height using standardized techniques. The overall prevalence of
      obesity and overweight in the present study amounted to 16%. Using logistic
      regression analysis, lack of exercise practice in the previous week in general
      [aOR = 1.352, 95% confidence interval (CI) = 1.066-1.941] or in the class (aOR =
      1.446, 95% CI = 1.083-1.931) were significantly associated with obesity. The
      present study showed that obesity among adolescent school boys in Abha City is a
      public health problem. There is a need for a national program in the country to
      prevent and control obesity among adolescents. The program should incorporate:
      dietary management of obesity, promotion of physical activity, health education
      campaigns and consideration of the possibility of providing facilities for
      practicing physical activity and exercise in the community.

PMID- 18039678
TI  - The accuracy of mother's touch to detect fever in children: a systematic review.
AB  - Universally, mothers often use touching to detect fever in their children. We
      perform a systematic review of published diagnostic studies evaluating the
      ability of mothers to detect fever in their children by touching. We found 10
      studies satisfying our inclusion criteria. The meta-analysis revealed a summary
      sensitivity of 89.2% and summary specificity of 50%-maternal touch is perhaps
      more useful to exclude fever rather than to 'rule in' fever. However, due to
      significant heterogeneity in the included studies, interpretation of the summary
      data is difficult.

PMID- 18039679
TI  - Helicobacter pylori infection and gastroesophageal reflux in asthmatic children.
AB  - The aim of this article is to investigate the prevalence of Helicobacter pylori
      (HP) infection, frequency of gastroesophageal reflux (GER), existence of atopy
      and levels of serum immunoglobulin E (IgE) in children with bronchial asthma. One
      hundred and thirty seven children who were diagnosed as bronchial asthma and/or
      wheezy child aged between 1 and 17 years were enrolled into the study. Peripheral
      venous blood samples were obtained to determine the total IgE and HP IgG antibody
      levels. GER was evaluated by the scintigraphic method and the presence of atopy
      was investigated by skin prick test. The study was conducted in 86 (62.8%) boys
      and 51 (37.2%) girls. HP IgG antibody levels were found negative in 125 (91.2%)
      and positive in 12 (8.8%) cases. GER was detected in 73 (53.7%) of the children.
      Forty-one (37.3%) children were accepted as atopic according to skin prick test
      results. The average total IgE levels of the participants was 168.89 +/- 270.76
      IU/ml. A significant difference could not be determined related to GER, atopy
      frequency and serum IgE levels between the cases who had HP antibody positivity
      or not. The present findings suggest that the rate of HP antibody positivity is
      low in patients with bronchial asthma and a significant difference could not be
      determined in GER, and atopy between patients with positive and negative HP
      antibodies. High atopy frequency found in our patient group raises the question
      of whether allergic diseases can be protective against fecal-oral infectious
      diseases.

PMID- 18039680
TI  - A recurrent intragenic genomic duplication, other novel mutations in NLRP7 and
      imprinting defects in recurrent biparental hydatidiform moles.
AB  - A complete hydatidiform mole (CHM) is an abnormal pregnancy with
      hyperproliferative vesicular trophoblast and no fetal development. Most CHM are
      sporadic and androgenetic, but recurrent HM have biparental inheritance (BiHM)
      with disrupted DNA methylation at differentially methylated regions (DMRs) of
      imprinted loci. Some women with recurrent BiHM have mutations in the NLRP7 gene
      on chromosome 19q13.42. Using bisulfite genomic sequencing at eight imprinted
      DMRs on DNA from two BiHMs, we found a pattern of failure to acquire or maintain
      DNA methylation at DMRs (PEG3, SNRPN, KCNQ1OT1, GNAS exon 1A) that normally
      acquire CpG methylation during oogenesis, but not at H19, which acquires CpG
      methylation during spermatogenesis. Secondary imprints at the GNAS locus showed
      variable abnormal patterns with both gain and loss of CpG methylation. We found
      novel missense and splice-site mutations in NLRP7 in women with non-familial
      recurrent BiHM. We identified and characterized a homozygous intragenic tandem
      duplication including exons 2 through 5 of NLRP7 that results in a predicted
      truncated protein in affected women of three unrelated Egyptian kindreds,
      suggesting a founder effect. Our findings firmly establish that NLRP7 mutations
      are a major cause of BiHM and confirm presence of a complex pattern of imprinting
      abnormalities in BiHM tissues.

PMID- 18039681
TI  - Daily practice effectiveness of a step-down treatment in comparison with a tight
      step-up for early rheumatoid arthritis.
AB  - OBJECTIVE: To study prospectively the daily practice effectiveness of a step-down
      early rheumatoid arthritis (RA) treatment strategy. METHODS: Patients with severe
      RA and no contra-indications were proposed step-down therapy, the others step-up.
      Step-down patients received a modified combination therapy in early RA (COBRA)
      regimen: sulphasalazine (SPS), 2 g daily, and methotrexate (MTX), 15 mg weekly,
      combined with step-down oral prednisolone (start 60 mg daily, fast tapering to
      7.5 mg over 6 weeks, discontinuation from week 28). At week 40, patients were
      randomized to maintenance therapy with either SPS or MTX if disease activity
      score-28 (DAS28) was acceptably low. The step-up group started disease-modifying
      anti-rheumatic drug (DMARD) monotherapy. In both groups, treatment was adjusted
      at follow-up, based on DAS28. DAS28, functionality Health Assessment
      Questionnaire (HAQ), adverse events, DMARD changes and steroid use were
      registered 4-monthly for 2 yrs. RESULTS: Nineteen patients received step-down and
      52 step-up treatment. More patients completed the first year without unplanned
      DMARD changes and without dosage adjustment and fewer had DMARD changes due to
      side effects or inefficacy in the step-down group compared with step-up, whereas
      the number of adverse events was comparable. MTX proved to be the most effective
      maintenance therapy after step-down. The DAS response, proportion of patients in
      remission, HAQ response and proportion of patients without disability at 4 months
      was higher in the step-down group. CONCLUSIONS: In daily practice, a step-down
      treatment strategy for early RA is more effective than a step-up approach.

PMID- 18039682
TI  - Target specificities of estrogen receptor-related receptors: analysis of binding
      sequences and identification of Rb1-inducible coiled-coil 1 (Rb1cc1) as a target
      gene.
AB  - Estrogen receptor-related receptors (ERRs) are orphan members of the nuclear
      receptor superfamily. A single AGGTCA sequence element preceded by three
      conserved nucleotides has been identified as a specific recognition motif of
      ERRs. Here we performed systematic analyses of target sequences on all three ERR
      subtypes, alpha, beta and gamma. In electrophoretic gel-mobility shift assay and
      transcriptional reporter assays, they exhibited similar patterns of recognition
      specificities, showing extremely broad ranges of target sequences. We searched a
      mouse promoter database for a gene carrying possible ERR-binding sequences. The
      Rb-1 inducible coiled-coil 1 (Rb1cc1) gene was found to contain two putative ERR
      binding elements, named response element (RE)-1 and RE-2, in the promoter region.
      In gene reporter assays, RE-2, but not RE-1, functioned as an effective cis
      regulatory element for transactivation by ERRalpha in the presence of a
      coactivator, peroxisome proliferator-activated receptor gamma coactivator-1alpha.
      Mutational analyses suggested that RE-2 is recognized by ERRalpha partly as a
      monovalent element, but also as a direct repeat motif separated by four spacer
      nucleotides. In vivo binding of ERRalpha to the Rb1cc1 promoter region was
      confirmed by the chromatin immunoprecipitation assay. Thus, Rb1cc1 is a target
      gene of ERRalpha, driven by a novel type of recognition sequence.

PMID- 18039683
TI  - Quantitative analysis of CUG-BP1 binding to RNA repeats.
AB  - CUG-binding protein 1 (CUG-BP1) is a member of the CUG-BP1 and ETR-3-like factors
      (CELF) family of RNA-binding proteins, and is involved in myotonic dystrophy type
      1 (DM1). Several mRNA targets of CUG-BP1 have been identified, including the
      insulin receptor, muscle chloride channel, and cardiac troponin T. On the other
      hand, CUG-BP1 has only a weak affinity for CUG repeats. We conducted quantitative
      binding assays to assess CUG-BP1 affinities for several repeat RNAs by surface
      plasmon resonance (SPR). Although we detected interactions between CUG-BP1 and
      CUG repeats, other UG-rich sequences actually showed stronger interactions.
      Binding constants of CUG-BP1 for RNAs indicated that the affinity for UG repeats
      was far stronger than for CUG repeats. We also found that N-terminal deletion
      mutant of CUG-BP1 has UG repeat-binding activity in a yeast three-hybrid system,
      although C-terminal deletion mutant does not. Our data indicates that CUG-BP1
      specifically recognized UG repeats, probably through cooperative binding of RNA
      recognition motifs at both ends of the protein. This is the first report of a
      binding constant for CUG-BP1 calculated in vitro.

PMID- 18039684
TI  - Anti-peptide antibodies for examining the conformation, molecular assembly and
      localization of an intracellular protein, ribosomal protein S6, in vivo.
AB  - Ribosomal protein S6 (rpS6) is known to relate to cell proliferation. Our recent
      proteome analysis of human metaphase chromosomes revealed the enrichment of rpS6
      during mitosis. Here, structure, localization and molecular assembly in vitro and
      in vivo of a human rpS6, were examined using antibodies (Abs) prepared by
      immunizing rabbits with synthetic peptides. Five peptides, Ser6-Asp20 (S6-1),
      Ile52-Gly66 (S6-2), Asp103-Gly117 (S6-3), Asn146-Lys160 (S6-4) and Arg178-Ile192
      (S6-5) were chosen as epitopes of human rpS6. These peptides except for S6-3
      induced strong Ab production, and with an enzyme-linked immunosorbent assay, anti
      S6-2, anti-S6-4 and anti-S6-5, showed high reactivity to recombinant rpS6 (r
      rpS6), while anti-S6-1 did not, suggesting that S6-2, S6-4 and S6-5 were exposed
      on the r-rpS6 surface, while S6-1 was less exposed or possessed a different
      conformation. The immunostaining of HeLa cells as well as isolated chromosomes
      suggested that rpS6 occurs in endoplasmic reticulum (ER) but less possible on
      chromosomes since no Abs showed localization of rpS6 to chromosomes. In addition,
      the immunostaining suggested that only S6-4 is exposed on the protein surface,
      while S6-2 and S6-5 are buried by the interaction with other macromolecules in
      HeLa cells. Present our result shows new possibility of antibodies as tools for
      structure-oriented cell biology.

PMID- 18039685
TI  - Biochemical characterization of phospholipids, sulfatide and heparin as potent
      stimulators for autophosphorylation of GSK-3beta and the GSK-3beta-mediated
      phosphorylation of myelin basic protein in vitro.
AB  - The stimulatory effects of SH (sulfatide and heparin) and two phospholipids (PI
      and PS) on autophosphorylation of GSK-3beta and the GSK-3beta-mediated
      phosphorylation of myelin basic protein (MBP) and two synthetic MBP peptides (M86
      and M156) were comparatively examined in vitro. It was found that (i) both PI and
      SH highly stimulated the GSK-3beta-mediated phosphorylation of MBP, but not
      glycogen synthase, and two MBP peptides through their direct binding to these
      substrates and (ii) both PI and heparin, as compared with sulfatide, highly
      stimulated autophosphorylation of GSK-3beta. The K(m) value of MBP for GSK-3beta
      was highly reduced and the V(max) value was significantly increased in the
      presence of these acidic modulators, which augmented further phosphorylation of
      MBP by the kinase. Under our experimental condition, similar stimulatory effects
      of PI and heparin were observed with the GSK-3beta-mediated phosphorylation of
      tau protein (TP) in vitro. These results presented here suggest that these two
      phospholipids and SH may function as effective stimulators for
      autophosphorylation of GSK-3beta and for the GSK-3beta-mediated high
      phosphorylation of SH-binding proteins, including MBP and TP, in the highly
      accumulated levels of these acidic and sulfated modulators in the brain.

PMID- 18039686
TI  - A strong exonic splicing enhancer in dystrophin exon 19 achieve proper splicing
      without an upstream polypyrimidine tract.
AB  - Proper splicing is known to proceed under the control of conserved cis-elements
      located at exon-intron boundaries. Recently, it was shown that additional
      elements, such as exonic splicing enhancers (ESEs), are essential for the proper
      splicing of certain exons, in addition to the splice donor and acceptor site
      sequences; however, the relationship between these cis-elements is still unclear.
      In this report, we utilize dystrophin exon 19 to analyse the relationship between
      the ESE and its upstream acceptor site sequences. Dystrophin exon 19, which
      maintains adequate splicing donor and acceptor consensus sequences, encodes
      exonic splicing enhancer (dys-ESE19) sequences. Splice pattern analysis, using a
      minigene reporter expressed in HeLa cells, showed that either a strong
      polypyrimidine tract (PPT) or a fully active dys-ESE19 is sufficient for proper
      splicing. Each of these two cis-elements has enough activity for proper exon 19
      splicing suggesting that the PPT, which is believed to be an essential cis
      element for splicing, is dispensable when the downstream exon contains a strong
      ESE. This compensation was only seen in living cells but not in 'in vitro
      splicing'. This suggests the possibility that the previous splicing experiments
      using an in vitro splicing system could underestimate the activity of ESEs.

PMID- 18039687
TI  - Recognition of a bulged RNA by peptides derived from the influenza NS1 protein.
AB  - A competition assay for RNA binding by the influenza virus NS1 protein using
      model RNAs, U6-45, corresponding to U6 snRNA revealed that deletion of each of
      the three bulged-out parts reduced the NS1 protein binding and, in contrast, by
      deleting all three of the bulged-out parts, simultaneously, and thus producing a
      double-stranded RNA, the binding was recovered. A common feature of target RNAs
      of the NS1 protein, U6 snRNA, poly(A) and viral RNA, is the stretch of 'bulged
      out' A residues. Thus, the NS1 protein was found to recognize either the stretch
      of 'bulged-out' A residues or dsRNA which is also a target of the NS1 protein.
      Furthermore, a basic peptide, NS1-2, derived from the helix-2 of the RNA binding
      site of NS1 protein was designed and its binding to the U6 snRNA was analysed by
      using a model RNA for U6 snRNA, U6-34. The NMR signals due to H8/H6 and H1' of U6
      34 were assigned and their changes upon binding of NS1-2 were analysed. It was
      indicated that NS1-2 interacts with the residues in the bulge-out region of U6
      34. These results suggest that NS1-2 recognizes the U6 snRNA in a similar manner
      to NS1 protein.

PMID- 18039688
TI  - Copper(II) inhibits in vitro conformational conversion of ovine prion protein
      triggered by low pH.
AB  - To gain insight into the conformational conversion of ovine prion protein
      (OvPrP(C)) at different pH values and/or in the presence of CuCl(2), the
      secondary structure of OvPrP(C) was analysed by circular dichroism (CD)
      spectroscopy. Copper treatment of OvPrP(C) under moderately acidic conditions (pH
      approximately 5.0-6.0) as well as physiological conditions (pH 7.4) also makes
      OvPrP(C) adopt protease-resistant and beta-sheet-rich conformation. However,
      under lower pH conditions (2.0-4.5) with copper treatment, OvPrP(C) gained higher
      alpha-helix structure. This study demonstrated that Cu(2+) can significantly
      modulate conformational conversion triggered by acidic pH, and this will provide
      therapeutic intervention approaches for prion diseases.

PMID- 18039689
TI  - Crystal and defect structures of La2/3 xLi3xTiO3 (x ~ 0.1) produced by a melt
      process.
AB  - The crystal and defect structures of coarse-grained crystals of La(2/3
      x)Li(3x)TiO3 grown from the melt by the Tammann-Stober method were studied by
      transmission electron microscopy and powder X-ray diffraction. The as-grown
      crystals of La(2/3-x)Li(3x)TiO3 have a Li-poor composition of
      La(0.57)Li(0.29)TiO3 and a diagonal-type unit cell of 2(1/2)a(p) x 2(1/2)a(p) x
      2a(p) with the tetragonal symmetry [space group: P4/nbm (#125)] due to both the
      La-cation ordering and the tilting of TiO6 octahedra. The secondary La2Ti2O7
      phase precipitates in the form of plates in the La(2/3-x)Li(3x)TiO3 phase with
      the orientation relationships of 001(p)//[100](La2Ti2O7) and
      {110}(p)//(001)(La2Ti2O7), which may cause detrimental effects to ionic
      conductivity.

PMID- 18039690
TI  - Methodological considerations for interpretation of rates of major haemorrhage in
      studies of anticoagulant therapy for atrial fibrillation.

PMID- 18039691
TI  - SIMAC (sequential elution from IMAC), a phosphoproteomics strategy for the rapid
      separation of monophosphorylated from multiply phosphorylated peptides.
AB  - The complete analysis of phosphoproteomes has been hampered by the lack of
      methods for efficient purification, detection, and characterization of
      phosphorylated peptides from complex biological samples. Despite several
      strategies for affinity enrichment of phosphorylated peptides prior to mass
      spectrometric analysis, such as immobilized metal affinity chromatography or
      titanium dioxide, the coverage of the phosphoproteome of a given sample is
      limited. Here we report a simple and rapid strategy, SIMAC (sequential elution
      from IMAC), for sequential separation of monophosphorylated peptides and multiply
      phosphorylated peptides from highly complex biological samples. This allows
      individual analysis of the two pools of phosphorylated peptides using mass
      spectrometric parameters differentially optimized for their unique properties. We
      compared the phosphoproteome identified from 120 mug of human mesenchymal stem
      cells using SIMAC and an optimized titanium dioxide chromatographic method. More
      than double the total number of identified phosphorylation sites was obtained
      with SIMAC, primarily from a 3-fold increase in recovery of multiply
      phosphorylated peptides.

PMID- 18039692
TI  - Is incentive spirometry effective following thoracic surgery?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was whether incentive spirometry is a useful
      intervention for patients after thoracic surgery. Altogether 255 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. We conclude that incentive spirometry is a relatively
      good measure of lung function and may be used to assess respiratory recovery in
      the days after thoracic surgery. Physiotherapy either with or without incentive
      spirometry reduces the incidence of postoperative complications and improves lung
      function but there is currently no evidence that incentive spirometry in itself
      could either replace or significantly augment the work of the physiotherapists.
      Clinicians should be aware that while incentive spirometry can provide an
      assessment of lung recovery, well-organised and regular physiotherapy remains the
      most effective mechanism to augment their patient's recovery and avoid
      postoperative complications.

PMID- 18039693
TI  - Gender and physical activity one year after myocardial revascularization for
      stable angina.
AB  - Improvement in physical activity (PA) is an important benefit for patients
      undergoing CABG. It is suggested that women make less improvement than men. Of
      568 patients (466 men and 102 women) undergoing an isolated primary CABG for
      stable angina (NYHA<4) pre- and 1-year postoperative PA was registered. The
      Corpus Christi Heart Project criteria are used for assessing PA. The different PA
      levels are coded from 1, the worst, to 5, the best. Preoperatively, female
      patients were older, in a higher NYHA class, and PA level was significantly
      different and lower 2.30+/-1.01 vs. 2.89+/-1.03 (P=0.000). At follow-up, the mean
      PA increased significantly for women (2.7+/-1.02) and men (3.2+/-1.06) (P=0.000).
      Despite this broad increase, 20% of men and 10% of women had a decreased PA.
      Multiple logistic regression analysis identified a preoperative high PA-level,
      diabetes, vascular- and pulmonary disease (odds ratio 7.11, 2.6, 2.3, 2.69) as
      variables that contribute independently to a worse PA for men and only high
      preoperative PA level (odds ratio 11.0) for women. This study confirms that
      patients with a preoperative high level PA are unlikely to improve PA, but in
      men, diabetes, vascular- and pulmonary disease are also independent risk factors.

PMID- 18039694
TI  - The possible reasons of limited rate freedom from atrial fibrillation after
      thoracoscopic microwave.

PMID- 18039695
TI  - Tricuspid valve prosthetic annuloplasty.

PMID- 18039696
TI  - Should stitch annuloplasty really be abandoned for developed flexible prosthetic
      band or ring in functional tricuspid regurgitation?

PMID- 18039697
TI  - The small saphenous vein as an alternative conduit for coronary artery bypass
      grafting.

PMID- 18039698
TI  - Short saphenous vein as a conduit in coronary artery bypass grafting.

PMID- 18039699
TI  - Bilateral internal thoracic artery harvesting: which harvesting technique is
      preferred?

PMID- 18039700
TI  - Cardioversion protocol for ventricular fibrillation: a more differentiated
      approach.

PMID- 18039701
TI  - Thrombolytic therapy or surgery as management of prosthetic valve thrombosis?

PMID- 18039702
TI  - The treatment of traumatic disruption of the thoracic aorta.

PMID- 18039703
TI  - The Pfam protein families database.
AB  - Pfam is a comprehensive collection of protein domains and families, represented
      as multiple sequence alignments and as profile hidden Markov models. The current
      release of Pfam (22.0) contains 9318 protein families. Pfam is now based not only
      on the UniProtKB sequence database, but also on NCBI GenPept and on sequences
      from selected metagenomics projects. Pfam is available on the web from the
      consortium members using a new, consistent and improved website design in the UK
      (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden
      (http://pfam.sbc.su.se/), as well as from mirror sites in France
      (http://pfam.jouy.inra.fr/) and South Korea (http://pfam.ccbb.re.kr/).

PMID- 18039704
TI  - Indirect readout in drug-DNA recognition: role of sequence-dependent DNA
      conformation.
AB  - DNA-binding drugs have numerous applications in the engineered gene regulation.
      However, the drug-DNA recognition mechanism is poorly understood. Drugs can
      recognize specific DNA sequences not only through direct contacts but also
      indirectly through sequence-dependent conformation, in a similar manner to the
      indirect readout mechanism in protein-DNA recognition. We used a knowledge-based
      technique that takes advantage of known DNA structures to evaluate the
      conformational energies. We built a dataset of non-redundant free B-DNA crystal
      structures to calculate the distributions of adjacent base-step and base-pair
      conformations, and estimated the effective harmonic potentials of mean force
      (PMF). These PMFs were used to calculate the conformational energy of drug-DNA
      complexes, and the Z-score as a measure of the binding specificity. Comparing the
      Z-scores for drug-DNA complexes with those for free DNA structures with the same
      sequence, we observed that in several cases the Z-scores became more negative
      upon drug binding. Furthermore, the specificity is position-dependent within the
      drug-bound region of DNA. These results suggest that DNA conformation plays an
      important role in the drug-DNA recognition. The presented method provides a tool
      for the analysis of drug-DNA recognition and can facilitate the development of
      drugs for targeting a specific DNA sequence.

PMID- 18039705
TI  - REDfly 2.0: an integrated database of cis-regulatory modules and transcription
      factor binding sites in Drosophila.
AB  - The identification and study of the cis-regulatory elements that control gene
      expression are important areas of biological research, but few resources exist to
      facilitate large-scale bioinformatics studies of cis-regulation in metazoan
      species. Drosophila melanogaster, with its well-annotated genome, exceptional
      resources for comparative genomics and long history of experimental studies of
      transcriptional regulation, represents the ideal system for regulatory
      bioinformatics. We have merged two existing Drosophila resources, the REDfly
      database of cis-regulatory modules and the FlyReg database of transcription
      factor binding sites (TFBSs), into a single integrated database containing
      extensive annotation of empirically validated cis-regulatory modules and their
      constituent binding sites. With the enhanced functionality made possible through
      this integration of TFBS data into REDfly, together with additional improvements
      to the REDfly infrastructure, we have constructed a one-stop portal for
      Drosophila cis-regulatory data that will serve as a powerful resource for both
      computational and experimental studies of transcriptional regulation. REDfly is
      freely accessible at http://redfly.ccr.buffalo.edu.

PMID- 18039706
TI  - Magnesium-binding studies reveal fundamental differences between closely related
      RNA triphosphatases.
AB  - The Chlorella virus RNA triphosphatase (cvRTPase) is involved in the formation of
      the RNA cap structure found at the 5'-end of the viral mRNAs and requires
      magnesium ions to mediate its catalytic activity. To extend our studies on the
      role of metal ions in phosphohydrolysis, we have used a combination of
      fluorescence spectroscopy, circular dichroism, denaturation studies and
      thermodynamic analyses to monitor the binding of magnesium ions to the cvRTPase.
      Using these techniques, the thermodynamic forces responsible for the interaction
      of metal ions with an RNA triphosphatase were also evaluated for the first time.
      Our thermodynamic analyses indicate that the initial association of magnesium
      with the cvRTPase is dominated by a favorable entropic effect and is accompanied
      by the release of eight water molecules from the enzyme. Moreover, both
      fluorescence spectroscopy and circular dichroism assays indicated that minor
      conformational changes were occurring upon magnesium binding. Mutational studies
      were also performed and confirmed the importance of three specific glutamate
      residues located in the active site of the enzyme for the binding of magnesium
      ions. Finally, in contrast to the yeast RNA triphosphatase, we demonstrate that
      the binding of magnesium ions to the cvRTPase does not lead to the stabilization
      of the ground state binding of the RNA substrate. Based on the results of the
      present study, we hypothesize that the binding of magnesium ions induces local
      conformational perturbations in the active site residues that ultimately
      positions the lateral chains of critical amino acids involved in catalysis. Our
      results highlight fundamental differences in the role of magnesium ions in the
      phosphohydrolase reactions catalyzed by the cvRTPase and the closely related
      yeast RNA triphosphatase.

PMID- 18039707
TI  - Structure of discontinuities in kinetoplast DNA-associated minicircles during S
      phase in Crithidia fasciculata.
AB  - Kinetoplast DNA (kDNA) is a novel form of mitochondrial DNA consisting of
      thousands of interlocked minicircles and 20-30 maxicircles. The minicircles
      replicate free of the kDNA network but nicks and gaps in the newly synthesized
      strands remain at the time of reattachment to the kDNA network. We show here that
      the steady-state population of replicated, network-associated minicircles only
      becomes repaired to the point of having nicks with a 3'OH and
      5'deoxyribonucleoside monophosphate during S phase. These nicks represent the
      origin/terminus of the strand and occur within the replication origins (oriA and
      oriB) located 180 degrees apart on the minicircle. Minicircles containing a new L
      strand have a single nick within either oriA or oriB but not in both origins in
      the same molecule. The discontinuously synthesized H strand contains single nicks
      within both oriA and oriB in the same molecule implying that discontinuities
      between the H-strand Okazaki fragments become repaired except for the fragments
      initiated within the two origins. Nicks in L and H strands at the origins persist
      throughout S phase and only become ligated as a prelude to network division. The
      failure to ligate these nicks until just prior to network division is not due to
      inappropriate termini for ligation.

PMID- 18039708
TI  - Retinoic acid modulates chromatin to potentiate tumor necrosis factor alpha
      signaling on the DIF2 promoter.
AB  - Transcriptional activation by nuclear hormone receptors is well characterized,
      but their cooperation with other signaling pathways to activate transcription
      remains poorly understood. Tumor necrosis factor alpha (TNFalpha) and all-trans
      retinoic acid (RA) induce monocytic differentiation of acute promyelocytic
      leukemia (APL) cells in a synergistic manner. We used the promoter of DIF2, a
      gene involved in monocytic differentiation, to model the mechanism underlying the
      cooperative induction of target genes by RA and TNFalpha. We show a functional RA
      response element in the DIF2 promoter, which is constitutively bound by
      PML/RARalpha in APL cells. RA stimulates release of corepressors and recruitment
      of chromatin modifying proteins and additional transcription factors to the
      promoter, but these changes cause only a modest induction of DIF2 mRNA. Co
      stimulation with RA plus TNFalpha facilitates binding of NF-kappaB to the
      promoter, which is crucial for full induction of transcription. Furthermore, RA
      plus TNFalpha greatly enhanced the level of RNA Pol II phosphorylation on the
      DIF2 promoter, via synergistic recruitment of TFIIH. We propose that RA mediates
      remodeling of chromatin to facilitate binding of transcription factors, which
      cooperate to enhance Pol II phosphorylation, providing a mechanism whereby
      nuclear receptors interact with other signaling pathways on the level of
      transcription.

PMID- 18039709
TI  - Transcription of Satellite III non-coding RNAs is a general stress response in
      human cells.
AB  - In heat-shocked human cells, heat shock factor 1 activates transcription of
      tandem arrays of repetitive Satellite III (SatIII) DNA in pericentromeric
      heterochromatin. Satellite III RNAs remain associated with sites of transcription
      in nuclear stress bodies (nSBs). Here we use real-time RT-PCR to study the
      expression of these genomic regions. Transcription is highly asymmetrical and
      most of the transcripts contain the G-rich strand of the repeat. A low level of G
      rich RNAs is detectable in unstressed cells and a 10(4)-fold induction occurs
      after heat shock. G-rich RNAs are induced by a wide range of stress treatments
      including heavy metals, UV-C, oxidative and hyper-osmotic stress. Differences
      exist among stressing agents both for the kinetics and the extent of induction
      (>100- to 80.000-fold). In all cases, G-rich transcripts are associated with
      nSBs. On the contrary, C-rich transcripts are almost undetectable in unstressed
      cells and modestly increase after stress. Production of SatIII RNAs after hyper
      osmotic stress depends on the Tonicity Element Binding Protein indicating that
      activation of the arrays is triggered by different transcription factors. This is
      the first example of a non-coding RNA whose transcription is controlled by
      different transcription factors under different growth conditions.

PMID- 18039710
TI  - The Leu22Pro tumor-associated variant of DNA polymerase beta is dRP lyase
      deficient.
AB  - Approximately 30% of human tumors characterized to date express DNA polymerase
      beta (pol beta) variant proteins. Two of the polymerase beta cancer-associated
      variants are sequence-specific mutators, and one of them binds to DNA but has no
      polymerase activity. The Leu22Pro (L22P) DNA polymerase beta variant was
      identified in a gastric carcinoma. Leu22 resides within the 8 kDa amino terminal
      domain of DNA polymerase beta, which exhibits dRP lyase activity. This domain
      catalyzes the removal of deoxyribose phosphate during short patch base excision
      repair. We show that this cancer-associated variant has very little dRP lyase
      activity but retains its polymerase activity. Although residue 22 has no direct
      contact with the DNA, we report here that the L22P variant has reduced DNA
      binding affinity. The L22P variant protein is deficient in base excision repair.
      Molecular dynamics calculations suggest that alteration of Leu22 to Pro changes
      the local packing, the loop connecting helices 1 and 2 and the overall
      juxtaposition of the helices within the N-terminal domain. This in turn affects
      the shape of the binding pocket that is required for efficient dRP lyase
      catalysis.

PMID- 18039711
TI  - STRALCP--structure alignment-based clustering of proteins.
AB  - Protein structural annotation and classification is an important and challenging
      problem in bioinformatics. Research towards analysis of sequence-structure
      correspondences is critical for better understanding of a protein's structure,
      function, and its interaction with other molecules. Clustering of protein domains
      based on their structural similarities provides valuable information for protein
      classification schemes. In this article, we attempt to determine whether
      structure information alone is sufficient to adequately classify protein
      structures. We present an algorithm that identifies regions of structural
      similarity within a given set of protein structures, and uses those regions for
      clustering. In our approach, called STRALCP (STRucture ALignment-based Clustering
      of Proteins), we generate detailed information about global and local
      similarities between pairs of protein structures, identify fragments (spans) that
      are structurally conserved among proteins, and use these spans to group the
      structures accordingly. We also provide a web server at
      http://as2ts.llnl.gov/AS2TS/STRALCP/ for selecting protein structures,
      calculating structurally conserved regions and performing automated clustering.

PMID- 18039712
TI  - DNA tape measurements of AraC.
AB  - A new method for measuring distances between points in the AraC-DNA complex was
      developed and applied. It utilizes variable lengths of single-stranded DNA that
      connect double-stranded regions containing the two half-site binding sequences of
      AraC. These distances plus the protein interdomain linker distances are
      compatible with two classes of structure for the dimeric AraC gene regulatory
      protein. In one class, the N-terminal regulatory arm of one dimerization domain
      is capable of interacting with the DNA-binding domain on the same polypeptide
      chain for a cis interaction. In the other class, the possible arm-DNA-binding
      domain interaction is trans, where it adds to the dimerization interface.

PMID- 18039713
TI  - The N-terminal domain of TWINKLE contributes to single-stranded DNA binding and
      DNA helicase activities.
AB  - The TWINKLE protein is a hexameric DNA helicase required for replication of
      mitochondrial DNA. TWINKLE displays striking sequence similarity to the
      bacteriophage T7 gene 4 protein (gp4), which is a bi-functional primase-helicase
      required at the phage DNA replication fork. The N-terminal domain of human
      TWINKLE contains some of the characteristic sequence motifs found in the N
      terminal primase domain of the T7 gp4, but other important motifs are missing.
      TWINKLE is not an active primase in vitro and the functional role of the N
      terminal region has remained elusive. In this report, we demonstrate that the N
      terminal part of TWINKLE is required for efficient binding to single-stranded
      DNA. Truncations of this region reduce DNA helicase activity and mitochondrial
      DNA replisome processivity. We also find that the gp4 and TWINKLE are
      functionally distinct. In contrast to the phage protein, TWINKLE binds to double
      stranded DNA. Moreover, TWINKLE forms stable hexamers even in the absence of
      Mg(2+) or NTPs, which suggests that an accessory protein, a helicase loader, is
      needed for loading of TWINKLE onto the circular mtDNA genome.

PMID- 18039714
TI  - Intracellular expression profiles measured by real-time PCR tomography in the
      Xenopus laevis oocyte.
AB  - Real-time PCR tomography is a novel, quantitative method for measuring localized
      RNA expression profiles within single cells. We demonstrate its usefulness by
      dissecting an oocyte from Xenopus laevis into slices along its animal-vegetal
      axis, extracting its RNA and measuring the levels of 18 selected mRNAs by real
      time RT-PCR. This identified two classes of mRNA, one preferentially located
      towards the animal, the other towards the vegetal pole. mRNAs within each group
      show comparable intracellular gradients, suggesting they are produced by similar
      mechanisms. The polarization is substantial, though not extreme, with around 5%
      of vegetal gene mRNA molecules detected at the animal pole, and around 50% of the
      molecules in the far most vegetal section. Most animal pole mRNAs were found in
      the second section from the animal pole and in the central section, which is
      where the nucleus is located. mRNA expression profiles did not change following
      in vitro fertilization and we conclude that the cortical rotation that follows
      fertilization has no detectable effect on intracellular mRNA gradients.

PMID- 18039715
TI  - Priorities for nucleotide trace, sequence and annotation data capture at the
      Ensembl Trace Archive and the EMBL Nucleotide Sequence Database.
AB  - The Ensembl Trace Archive (http://trace.ensembl.org/) and the EMBL Nucleotide
      Sequence Database (http://www.ebi.ac.uk/embl/), known together as the European
      Nucleotide Archive, continue to see growth in data volume and diversity. Selected
      major developments of 2007 are presented briefly, along with data submission and
      retrieval information. In the face of increasing requirements for nucleotide
      trace, sequence and annotation data archiving, data capture priority decisions
      have been taken at the European Nucleotide Archive. Priorities are discussed in
      terms of how reliably information can be captured, the long-term benefits of its
      capture and the ease with which it can be captured.

PMID- 18039716
TI  - CandidaDB: a multi-genome database for Candida species and related
      Saccharomycotina.
AB  - CandidaDB (http://genodb.pasteur.fr/CandidaDB) was established in 2002 to provide
      the first genomic database for the human fungal pathogen Candida albicans. The
      availability of an increasing number of fully or partially completed genome
      sequences of related fungal species has opened the path for comparative genomics
      and prompted us to migrate CandidaDB into a multi-genome database. The new
      version of CandidaDB houses the latest versions of the genomes of C. albicans
      strains SC5314 and WO-1 along with six genome sequences from species closely
      related to C. albicans that all belong to the CTG clade of Saccharomycotina
      Candida tropicalis, Candida (Clavispora) lusitaniae, Candida (Pichia)
      guillermondii, Lodderomyces elongisporus, Debaryomyces hansenii, Pichia stipitis
      and the reference Saccharomyces cerevisiae genome. CandidaDB includes sequences
      coding for 54 170 proteins with annotations collected from other databases,
      enriched with illustrations of structural features and functional domains and
      data of comparative analyses. In order to take advantage of the integration of
      multiple genomes in a unique database, new tools using pre-calculated or user
      defined comparisons have been implemented that allow rapid access to comparative
      analysis at the genomic scale.

PMID- 18039717
TI  - Fasting versus nonfasting triglycerides: implications for laboratory
      measurements.

PMID- 18039718
TI  - Description and validation of a novel real-time RT-PCR enterovirus assay.
AB  - BACKGROUND: Enteroviruses are a leading cause of aseptic meningitis in adult and
      pediatric populations. We describe the development of a real-time RT-PCR assay
      that amplifies a small target in the 5' nontranslated region upstream of the
      classical Rotbart enterovirus amplicon. The assay includes an RNA internal
      control and incorporates modified nucleotide chemistry. METHODS: We evaluated the
      performance characteristics of this design and performed blinded parallel testing
      on clinical samples, comparing the results with a commercially available RT-PCR
      assay (Pan-Enterovirus OligoDetect kit) that uses an enzyme immunoassay-like
      plate end detection. RESULTS: We tested 778 samples and found 14 discrepant
      samples between the 2 assays. Of these, the real-time assay detected 6 samples
      that were negative by the OligoDetect kit, 5 of which were confirmed as positive
      by sequence analysis using an alternative primer set. Eight discrepant samples
      were positive by the OligoDetect kit and real-time negative, with 6 confirmed by
      sequencing. Overall, detection rates of 97% and 96% were obtained for the
      OligoDetect kit and real-time assays, respectively. Sequence analysis revealed
      the presence of a number of single nucleotide polymorphisms in the targeted
      region. The comparative sensitivities of the 2 assays were equivalent, with the
      limit of detection for the real-time assay determined to be approximately 430
      copies per milliliter in cerebrospinal fluid. CONCLUSIONS: This novel real-time
      enterovirus assay is a sensitive and suitable assay for routine clinical testing.
      The presence of single nucleotide polymorphisms can affect real-time PCR assays.

PMID- 18039720
TI  - Monitoring rheumatoid arthritis synovitis with 99mTc-anti-CD3.
AB  - The aim of this study was to investigate the feasibility of using a monoclonal
      antibody (OKT3) labelled with technetium-99m (99mTc) to monitor disease activity
      in patients with rheumatoid arthritis. We evaluated 38 patients who were
      diagnosed with rheumatoid arthritis and classified as Classes II and III after
      functional assessment (according to the revised criteria specified by the
      American College of Rheumatology). Two sets of planar anterior images of the
      patients' wrists, metacarpophalangeal and interphalangeal joints, elbows,
      shoulders and knees joints were obtained 1 h and 3 h after the injection of 99mTc
      OKT3. The scintigraphic findings showed significant correlation (p<0.05) between
      the radiopharmaceutical accumulation of 99mTc-OKT3 and swollen joints, tender
      joints and the visual analogue scale. They were able to differentiate patients in
      remission from patients with active synovitis, according to DAS 28. In contrast,
      there was no correlation between the radiopharmaceutical accumulation and the
      patients' age, gender, duration of disease or erythrocyte sedimentation rate. A
      relatively high disease activity score of 28 joints (4.08+/-1.74) was found in
      the majority of patients. In conclusion, 99mTc-OKT3 scintigraphy is a reliable
      and objective method for detecting synovial activity, and can be used to observe
      disease prognosis.

PMID- 18039719
TI  - Serum uric acid and risk of cardiovascular mortality: a prospective long-term
      study of 83,683 Austrian men.
AB  - BACKGROUND: The role of serum uric acid (SUA) as an independent risk factor for
      cardiovascular disease (CVD) remains controversial, and little is known about its
      prognostic importance for mortality from congestive heart failure (CHF) and
      stroke. Few large-scale epidemiologic studies with sufficient follow-up have
      addressed the association of SUA and CVD mortality in apparently healthy men
      across a wide age range. METHODS: A cohort of 83 683 Austrian men (mean age, 41.6
      years) was prospectively followed for a median of 13.6 years. We used Cox
      proportional hazards models adjusted for established risk factors to evaluate SUA
      as an independent predictor for CVD mortality. RESULTS: The highest quintile of
      SUA concentration (>398.81 mumol/L) was significantly related to mortality from
      CHF (P = 0.03) and stroke (P <0.0001); adjusted hazard ratios (95% confidence
      interval) for the highest vs lowest quintiles of SUA were 1.51 (1.03-2.22) and
      1.59 (1.23-2.04), respectively. SUA was not associated, however, with mortality
      from acute, subacute, or chronic forms of coronary heart disease (CHD) after
      adjustment for potential confounding factors (P = 0.12). Age was a significant
      effect modifier for the relation of SUA to fatal CHF (P = 0.05), with markedly
      stronger associations found in younger individuals. CONCLUSIONS: Our study
      demonstrates for the first time in a large prospective male cohort that SUA is
      independently related to mortality from CHF and stroke. Although increased SUA is
      not necessarily a causal risk factor, our results suggest the clinical importance
      of monitoring and intervention based on the presence of an increased SUA
      concentration, especially because SUA is routinely measured.

PMID- 18039721
TI  - Designing equivalent treatment regimens for prostate radiotherapy based on
      equivalent uniform dose.
AB  - The purpose of this work was to determine alternative radiotherapy (RT) regimens
      that are biologically equivalent to clinically proven treatments using different
      RT modalities or different fractionation schemes. The concept of equivalent
      uniform dose (EUD) is used with the linear quadratic model to determine
      equivalent treatment regimens using two representative sets of parameters derived
      from clinical data: (i) alpha/beta = 3.1 Gy and alpha = 0.15 Gy(-1), and (ii)
      alpha/beta = 1.5 Gy and alpha = 0.04 Gy(-1). The EUD values for the critical
      structure (rectum) are also calculated. Representative dose volume histograms
      were used to account for dose inhomogeneities for different RT modalities. A
      series of alternative and equivalent fractionation regimens that can be used with
      different radiotherapy modalities for localized prostate cancer were determined.
      For example, the alternative regimens, calculated with the alpha/beta ratio of
      3.1 Gy, that would be biologically equivalent to external beam RT (EBRT) of 76 Gy
      (38x2.0 Gy) include: EBRT hypofractionation of 21x3.0 Gy; I-125 implant of 156
      Gy; Pd-103 implant of 128 Gy; high dose rate (HDR) brachytherapy of 4x10.5 Gy; I
      125 implant of 65 Gy combined with EBRT of 23x2.0 Gy; and HDR brachytherapy of
      3x5.9 Gy combined with EBRT of 23x2.0 Gy. Similar data for other parameters are
      also presented. With caution, the data presented may be useful in designing
      clinical trials to explore new RT strategies, such as image-guided intensity
      modulated RT.

PMID- 18039722
TI  - An investigation into patient and staff doses from X-ray angiography during
      coronary interventional procedures.
AB  - Radiation doses to patients from interventional coronary X-ray procedures are
      relatively high when compared with conventional radiographic procedures. These
      high patient doses can translate into high staff doses owing to scattered
      radiation. This study investigates patient doses by means of dose-area product
      (DAP) meters installed in six rooms in two hospitals. DAP measurements in each
      room ranged from 28.0-39.3 Gy cm2 for coronary angiography and from 61.3-92.8 Gy
      cm2 for percutaneous transluminal coronary angioplasty, with the mean effective
      doses calculated to range between 5.1-6.6 mSv and 11.2-17.0 mSv, respectively.
      These values are comparable with those found in recent literature. DAP
      measurements were found to correlate strongly (correlation coefficient of 79%)
      with patient weight. The non-uniform scatter radiation fields surrounding the
      irradiated area during coronary angiography were also investigated using a tissue
      equivalent phantom and an ionization chamber. Exposure rates of scattered
      radiation from digital acquisition were found to be around 16 times higher than
      those generated from fluoroscopy, and oblique-angled imaging led to greater
      amounts of scatter owing to the increase in related exposure factors. The
      distribution of scatter from oblique projections confirms that X-ray photons in
      the diagnostic energy range are preferentially scattered backwards, toward the X
      ray tube. These concepts are a major consideration when training individuals
      working in the angiography suite in order to keep doses "as low as reasonably
      practicable".

PMID- 18039723
TI  - Radiation risks in interventional radiology.
AB  - The number, diversity and complexity of interventional radiological examinations
      have all increased markedly in recent years, and it is widely recognized that
      some of these procedures carry greater risks than many other radiological
      procedures. This Commentary uses a meeting on "Radiation Protection in
      Interventional Radiology" held at the British Institute of Radiology on 28 March
      2007 as a template to discuss recent progress in this area, some current problems
      and plans for the future.

PMID- 18039724
TI  - The use of mixed methodology in evaluating complex interventions: identifying
      patient factors that moderate the effects of a decision aid.
AB  - BACKGROUND: Mixed method research, the combined use of qualitative and
      quantitative methods, is increasingly popular in health services research,
      especially as a way to examine 'complex interventions'. This paper seeks to
      provide a case example of the use of mixed methods in the analysis of a complex
      intervention (a computerized interactive decision aid) to test whether their use
      affords insights into potential moderators of the intervention (i.e. patient
      factors that were associated with the impact of the intervention). METHODS: We
      conducted a pragmatic randomized controlled trial (n=149) of a decision aid in
      women attending their primary care practitioners with menorrhagia. Alongside the
      trial, a qualitative study was conducted with interviews with a sample of women
      who had received the intervention (n=18). Hypotheses generated by the qualitative
      study were used to inform subsequent quantitative subgroup analyses. RESULTS: The
      results from both studies showed that the decision aid was broadly beneficial.
      The qualitative study found that women with less formal education reported
      greater levels of benefit from the intervention. However, quantitative analyses
      of formal education as a moderator of treatment effect found that the
      intervention provided the greatest benefit in women with greater formal
      education. The findings of the qualitative and quantitative studies thus
      demonstrated a significant inter-method discrepancy. Possible reasons for this
      discrepancy are discussed. CONCLUSIONS: Mixed methods can illuminate different
      aspects of an intervention or provide greater insight into particular issues.
      Health service researchers need to be aware that the qualitative and quantitative
      results may be discrepant, and methods need to be developed to deal with such
      discrepancies. However, exploring seemingly discrepant results can lead to
      greater insight and the development of new hypotheses and avenues of research.

PMID- 18039725
TI  - Intensification of therapy and no increase in body mass index with longer disease
      duration in type 2 diabetes mellitus (ZODIAC-5).
AB  - BACKGROUND: Decreased insulin sensitivity and beta-cell failure are the two key
      components in the pathogenesis of type 2 diabetes mellitus (T2DM). Secondary
      treatment failure is often attributed to the development of obesity-related
      insulin resistance in combination with continued loss of beta-cell function.
      OBJECTIVE: Assess metabolic control, body mass index (BMI) and treatment in
      relationship to diabetes duration to study these mechanisms. METHODS: Cross
      sectional study of 7875 patients with T2DM in primary care in The Netherlands.
      Clinical data and laboratory results were obtained for the 2005 annual visit.
      Patients were grouped according to diabetes duration in 2-year intervals. Each
      step in the traditional treatment sequence was considered as a sign of
      progression of beta-cell failure. RESULTS: Complete data regarding duration and
      treatment were available for 6850 patients (87%). After the initial years
      following diagnosis, treatment with diet alone decreases and oral hypoglycaemic
      agents (OHA) are prescribed to an increasing percentage of patients. Treatment
      with OHA diminishes after approximately 10 years following diagnosis and
      treatment with insulin increases until approximately two-thirds of patients with
      diabetes duration of more than 20 years are being treated with insulin. BMI does
      not increase with longer disease duration. CONCLUSION: The concept of beta-cell
      failure as the primary determinant of the chronic progression of T2DM is
      supported by these results, whereas a deterioration of obesity-related insulin
      sensitivity as indicator is not supported.

PMID- 18039726
TI  - Children's active free play in local neighborhoods: a behavioral mapping study.
AB  - Many Australian children are more sedentary than they should be, and almost one
      in five are currently overweight or obese. Some children may face difficulties
      finding opportunities to be active, having poor access to safe public open spaces
      or having low independent mobility limiting their access to places to play. This
      study aimed to examine children's access to places in their neighborhood for
      active free play and how these vary by age, sex and socioeconomic status (SES).
      Behavioral maps of the local neighborhood were completed by children (8-12 years)
      from five primary schools across different areas of Melbourne. Children living in
      low SES outer-urban neighborhoods had to travel greater distances to access local
      parks compared with those in inner-urban mid and high SES areas. One-third (32%)
      of children reported an independent mobility range of <100 m from home. In
      conclusion, for some children opportunities to engage in active free play in the
      local neighborhood may be limited due to lack of parks in close proximity to home
      and restricted independent mobility. It is important to collaborate with local
      governments, urban planners and community groups to improve access to
      neighborhood parks and to promote a sense of neighborhood safety.

PMID- 18039727
TI  - The impact of an appearance-based educational intervention on adolescent
      intention to use sunscreen.
AB  - During adolescence, there is a steady decline in the use of sun protection and
      increased use of indoor tanning lights. Previous health education efforts have
      changed knowledge but not these behaviors. Middle school students (n=113)
      received a single educational class that included personal viewing of skin
      changes visible under ultraviolet (UV) filtered light. Pre-/post-surveys assessed
      past, current and future intent to use sunscreen, as well as sun benefit and sun
      risk attitudes. Prior to the session, 42% were sunscreen non-users and 21% were
      consistent users. At post-test, one-third of students who had not previously
      intended to use sunscreen in the next month now intended to use it. Among
      students who had seen skin damage, 59% reported intention to use sunscreen in the
      next month versus 35% who did not see skin changes (P = 0.04). Viewing sun damage
      was an independent predictor of intent to use sunscreen in the next month (OR
      2.9, P = 0.04), as was older age (OR 2.6, P = 0.04) and previous consistent
      sunscreen use (OR 6.1, P = 0.004). A brief educational intervention that
      emphasizes risk-to-appearance and personalizes the risks of UV exposure has the
      potential to influence early adolescent sun protection. Long-term studies of this
      approach are needed.

PMID- 18039729
TI  - Bunny hops and creative thinking about getting youngsters active.

PMID- 18039728
TI  - Comparison of three methods of pre-employment medical evaluations.
AB  - BACKGROUND: Increasing efforts are being made to prevent sickness absence and to
      increase worker efficiency, including the use of costly pre-employment medical
      assessment of white-collar workers and labourers, excluding occupations for which
      medical supervision is required by law. AIM: To investigate whether filling out
      an occupational health questionnaire (OHQ) as pre-employment assessment was more
      efficient than previously used protocols which included a physical examination
      and laboratory tests performed for each applicant. METHODS: Retrospective study
      comparing three groups of job applicants: Group A--applicants examined by an
      occupational physician (OP); Group B--applicants examined by a general
      practitioner (GP) whose medical records were subsequently evaluated by an OP and
      Group C--the applicant filled out an OHQ which was evaluated by an OP. RESULTS:
      The study included 1940 pre-employment assessments divided into groups A (618), B
      (256) and C (1066). The restriction rate was 2.1, 1.2 and 2.3%, respectively. The
      lowest restriction rate (1.4%) was among applicants 29 years old and younger and
      the highest one (3.6%) among 50 years and older. The most frequent diagnoses
      among restricted applicants were musculoskeletal and circulatory diseases (15 and
      12%, respectively). CONCLUSIONS: The restriction rate achieved by medical
      examinations either done by an OP (Group A) or by a GP (Group B) was the same as
      in OHQ (Group C). The use of a self-administered questionnaire evaluated by an OP
      is the preferred method of pre-employment evaluation for non-hazardous
      occupations.

PMID- 18039730
TI  - Childhood chronic pain and health care professional interactions: shaping the
      chronic pain experiences of children.
AB  - Children with chronic pain meet numerous healthcare professionals during their
      search to understand their pain. Through semi-structured interviews, this
      qualitative study sought to understand the experiences of five children with
      chronic pain as they encountered healthcare professionals. In the majority of
      these interactions, children reported feeling misunderstood, disbelieved and
      abandoned. The findings of this study demonstrate that children's experiences
      with professionals influence their approach towards current and future healthcare
      encounters. All children discussed their guarded relationships with healthcare
      providers. Children also developed negative perceptions about their pain, in
      particular believing that their experience with chronic pain was life
      threatening, and demanded major life adjustments. Interactions with healthcare
      professionals have a tremendous influence on children's perceptions and chronic
      pain experiences. In order to better understand and care for children with
      chronic pain, it is essential that healthcare professionals provide children with
      the opporunity to communicate their unique experiences with pain.

PMID- 18039731
TI  - Here's an idea: ask the users! Young people's views on navigation, design and
      content of a health information website.
AB  - Use of the internet to provide health information to young people is a relatively
      recent development. Few studies have explored young people's views on how they
      use internet health websites. This study investigated the navigation, design and
      content preferences of young people using the Children First for Health (CFfH)
      website. Young people from five secondary schools completed an internet site
      navigation exercise, website evaluation questionnaire and participated in
      informal discussions. Of the participants, 45 percent visited the website section
      aimed at older adolescents within their first two clicks, regardless of their
      age. There were conflicting preferences for design and strong preference for
      gender-specific information on topics such as appearance, relationships, fitness
      and sexual health. The findings indicate the importance of gaining young people's
      views to ensure that health information websites meet the needs of their intended
      audience. Cooperation from schools can facilitate the process of gaining young
      people's views on internet website navigation, design and content.

PMID- 18039732
TI  - Guilt and shame: experiences of parents of self-harming adolescents.
AB  - This paper reports the findings of a qualitative study that used a hermeneutic
      phenomenological methodology to develop insights into the experience of parents
      of young people who engage in self-harming behaviour. Six mothers (and one father
      who accompanied his wife) participated in the study. Findings reveal that mothers
      experienced guilt and shame, and that these feelings shaped their reactions and
      responses. These mothers described experiencing emotional dilemmas, such as the
      degree to which they could be responsible, uncertainty about how to understand
      self harm, and the best course of action to take with their child. They also
      encountered difficulties in combating the negative emotional effects for
      themselves and other family members. Findings provide insights that can help
      nurses and family health workers to understand and assist parents with greater
      effectiveness; by maintaining a non-judgemental stance, acknowledging the
      difficulties of their experiences, encouraging confidence in their parenting
      abilities, and promoting effective stress management strategies.

PMID- 18039733
TI  - Discussing childhood overweight and obesity with parents: a health communication
      dilemma.
AB  - Childhood obesity has reached alarming levels and the problem has assumed great
      significance for health care staff who work with overweight children and their
      families. Anecdotal accounts of the difficulties that may emerge when health care
      providers communicate that a child's weight is outside of the normal range, were
      a key stimulus for this review. A local government health department commissioned
      a review of literature on communicating with parents about childhood overweight
      and obesity. Literature concerned with communicating a child's overweight to
      parents was limited and, as a result, this review draws upon a disparate body of
      literature to examine what is known and what might be helpful for health care
      providers when discussing a child's weight with the child and parents. This paper
      identifies a range of factors influencing communication between health care
      workers and parents and offers a number of practical approaches and strategies
      for facilitating successful communication between health practitioners and the
      parents of children.

PMID- 18039735
TI  - Phosphorus acquisition by Chlamydomonas acidophila under autotrophic and osmo
      mixotrophic growth conditions.
AB  - Chlamydomonas acidophila Negoro is a green algal species abundant in acidic
      waters where inorganic phosphorus (P(i)) and carbon (CO(2)) are considered the
      most important growth-limiting nutrients for the phytoplankton. This paper
      describes the P(i) uptake and growth kinetics under varying carbon supply by
      cultivating the alga autotrophically, with and without CO(2) aeration, and osmo
      mixotrophically with glucose under low P(i) conditions at pH 2.7. The low minimum
      cellular phosphorus quota (Q(0); ranging from 0.6 to 1.1 mmol P mol(-1) C)
      suggested P(i)-limiting conditions under all different modes of carbon supply,
      and was lowest under CO(2)-aerated conditions. The threshold P(i) concentration
      for growth did not vary from zero, suggesting no detectable metabolic costs.
      Maximum P(i)-uptake rates (V(max)) were a better indication of P(i) limitation
      when compared with the affinity constant for P(i) uptake (K(m)), as V(max) was
      only high under P(i)-limited conditions whereas K(m) was low under both P(i)
      limited and P(i)-replete conditions. Osmo-mixotrophic growth conditions did not
      result in decreased extracellular phosphatase activity, but often resulted in
      physiological characteristics comparable with CO(2)-aerated cells, suggesting
      intracellular CO(2) production by glucose respiration. In addition, at low CO(2)
      and in autotrophic conditions, C. acidophila had a higher Q(0), lower dissolved
      organic carbon concentration, lower maximum P(i)-uptake rates, and lower
      phosphatase activity, suggesting that growth was co-limited by CO(2) and P(i).
      Furthermore, cells may respond physiologically to both nutrient limitations
      simultaneously.

PMID- 18039734
TI  - Emotional and rational product appeals in televised food advertisements for
      children: analysis of commercials shown on US broadcast networks.
AB  - The aggressive advertising and marketing of high caloric food products to
      children is implicated as a potential causative factor in the childhood obesity
      epidemic. This study analyzed 147 commercials appearing during children's
      programming on U.S. broadcast networks for a wide range of potential emotional
      and rational advertising appeals. The most prominent emotional appeals were
      fun/happiness and play followed by fantasy/ imagination, social enhancement/peer
      acceptance, and coolness/hipness. Many of the products used the term ;super
      charged' or a similar adjective to describe the powerful taste or other physical
      properties of the product. More than one-third of all the commercials used a
      fruit appeal or association. Statements or depictions that a product was healthy
      or nutritious were quite rare among the commercials. This seems to imply that
      health and nutrition claims are understood by food marketers to not be salient
      concerns among children and as such are not a selling point to children.
      Commercials for high sugar cereal products and fast food restaurants differed in
      several respects. This study can serve to guide child health care professionals
      and other child advocates in designing measures that counter food advertising
      messages directed at children.

PMID- 18039736
TI  - Inhibition of catalase activity as an early response of Arabidopsis thaliana
      cultured cells to the phytotoxin fusicoccin.
AB  - In Arabidopsis thaliana cells, fusicoccin (FC) treatment induced an early and
      marked increase in the extracellular H(2)O(2) level. It also increased the huge
      hypo-osmotic stress-induced oxidative wave and, in addition, prevented the
      H(2)O(2) peak drop. These effects were apparently not linked to changes in either
      cytoplasmic pH or cytoplasmic free calcium concentration, since they occurred
      independently of the activity state of the plasma membrane (PM) H(+)-ATPase and
      neither influx nor efflux of (45)Ca(2+) was modified by FC. In the presence of
      diphenylene iodonium (DPI), inhibiting the PM NADPH oxidase presumably
      responsible for reactive oxygen species (ROS) production, no apoplastic H(2)O(2)
      development was detected either with or without FC. However, no increase in DPI
      sensitive ferricyanide reduction, but rather a gradual decrease, occurred with
      FC. These results suggested that the H(2)O(2) increase observed with FC was not
      due to a overproduction of ROS but, more probably, to a reduced capability of FC
      treated cells to degrade the H(2)O(2) formed. This view, at first supported by
      the finding that FC-treated cells failed to break down exogenously supplied
      H(2)O(2), was clearly confirmed by a series of measurements on exogenous catalase
      activity, tested in cell-free media of FC-treated samples. This assay, in fact,
      allowed ascertainment and partial characterization of an as yet unidentified
      factor increasingly accumulating in the incubation medium of FC-treated cells,
      behaving as a non-competitive catalase inhibitor and able to reduce markedly the
      cell's capability for H(2)O(2) scavenging.

PMID- 18039737
TI  - Effects of bacteria on enhanced metal uptake of the Cd/Zn-hyperaccumulating
      plant, Sedum alfredii.
AB  - To investigate the effects of bacteria (Burkholderia cepacia) on metal uptake by
      the hyperaccumulating plant, Sedum alfredii, a hydroponic experiment with
      different concentrations of Cd and Zn was conducted. It was found that
      inoculation of bacteria on S. alfredii significantly enhanced plant growth (up to
      110% with Zn treatment), P (up to 56.1% with Cd treatment), and metal uptake (up
      to 243% and 96.3% with Cd and Zn treatment, respectively) in shoots, tolerance
      index (up to 134% with Zn added treatment), and better translocation of metals
      (up to 296% and 135% with Cd and Zn treatment, respectively) from root to shoot.
      In the ampicillin added treatment with metal addition, stimulation of organic
      acid production (up to an increase of 133% of tartaric acid with Cd treatment) by
      roots of S. alfredii was observed. The secretion of organic acids appears to be a
      functional metal resistance mechanism that chelates the metal ions
      extracellularly, reducing their uptake and subsequent impacts on root
      physiological processes.

PMID- 18039738
TI  - Changes in hydraulic conductivity, mechanical properties, and density reflecting
      the fall in strain along the lateral roots of two species of tropical trees.
AB  - Roots have been described as having larger vessels and so greater hydraulic
      efficiency than the stem. Differences in the strength and stiffness of the tissue
      within the root system itself are thought to be an adaptation to the loading
      conditions experienced by the roots and to be related to differences in density.
      It is not known how potential mechanical adaptations may affect the hydraulic
      properties of the roots. The change in strength, stiffness, conductivity,
      density, sapwood area, and second moment of area distally along the lateral roots
      of two tropical tree species in which the strain is known to decrease rapidly was
      studied and the values were compared with those of the trunk. It was found that
      as the strain fell distally along the roots, so did the strength and stiffness of
      the tissue, whereas the conductivity increased exponentially. These changes
      appeared to be related to differences in density. In contrast to the distal-most
      roots, the tissue of the proximal roots had a lower conductivity and higher
      strength than that of the trunk. This suggests that mechanical requirements on
      the structure rather than the water potential gradient from roots to branches are
      responsible for the general pattern that roots have larger vessels than the stem.
      In spite of their increased transectional area, the buttressed proximal roots
      were subjected to higher levels of stress and had a lower total conductivity than
      the rest of the root system.

PMID- 18039739
TI  - Gene expression during the induction, maintenance, and release of dormancy in
      apical buds of poplar.
AB  - The perennial lifestyle of trees is characterized by seasonal cycles of growth
      and dormancy. The recurrent transitions into and out of dormancy represent an
      adaptation mechanism that largely determines survival and, hence, the
      geographical distribution of tree species. To understand better the molecular
      basis of bud dormancy, cDNA-amplified fragment length polymorphism (AFLP)
      transcript profiling was used to map differential gene expression during dormancy
      induction, dormancy, dormancy release by chilling, and subsequent bud break in
      apical buds of poplar (Populus tremulaxP. alba). Unexpectedly, besides poplar
      transcript sequences, the cDNA-AFLP profiles revealed sequence signatures
      originating from a complex bacterial community, which was more pronounced during
      dormancy and displayed temporal dynamics in composition and complexity. Based on
      poplar gene expression dynamics, processes and potential regulators during
      different phases of dormancy are described. Novel genes were linked to a crucial
      transitory step in dormancy induction, and to dormancy release through chilling,
      a molecularly unresolved phenomenon. One WRKY- and two ERF-related transcription
      factors were similarly expressed during the transition to dormancy in apical and
      axillary buds. These regulatory genes could be involved in the differentiation of
      stipule-like leaf organs protecting the bud, or act during the growth-dormancy
      transition in the meristem, revealing commonalities between para- and
      endodormancy.

PMID- 18039740
TI  - Arabinogalactan proteins as molecular markers in Arabidopsis thaliana sexual
      reproduction.
AB  - Some of the most important changes that occur in plants during sexual
      reproduction involve the transition from a sporophytic to a gametophytic type of
      development. In this paper, these changes were evaluated for Arabidopsis
      thaliana. The results obtained clearly show differences in the pattern of
      distribution of specific arabinogalactan protein (AGP) sugar epitopes, during
      anther and ovule development. AGPs are hydroxyproline-rich glycoproteins that are
      massively glycosylated and ubiquitous in plants. The molecular mechanism of
      action of AGPs is still unknown, mainly due to the difficulties posed by the
      complex saccharide chains. However, the complex structure of the sugar fraction
      of AGPs makes them a potential source of signalling molecules. The selective
      labelling obtained with AGP mAbs JIM8, JIM13, MAC207, and LM2, during Arabidopsis
      pollen and pistil development, suggests that some AGPs can work as markers for
      gametophytic cell differentiation. Specific labelling of the first gametophytic
      cells in the pistil, the strong labelling of the secretory cells of the embryo
      sac, the synergid cells, and the labelling of the integument micropylar cells,
      apparently outlining the pollen tube pathway into its final target, the embryo
      sac, have all been shown. In the anthers, the specific labelling of gametophytic
      cells, and of the male gametes that travel along the pollen tube, may indicate
      AGP epitopes acting as signals for the pollen tube to reach its final destiny.
      The specific labelling of cells destined to go into programmed cell death is also
      discussed.

PMID- 18039741
TI  - Nitric oxide function and signalling in plant disease resistance.
AB  - Nitric oxide (NO) is one of only a handful of gaseous signalling molecules. Its
      discovery as the endothelium-derived relaxing factor (EDRF) by Ignarro
      revolutionized how NO and cognate reactive nitrogen intermediates, which were
      previously considered to be toxic molecules, are viewed. NO is now emerging as a
      key signalling molecule in plants, where it orchestrates a plethora of cellular
      activities associated with growth, development, and environmental interactions.
      Prominent among these is its function in plant hypersensitive cell death and
      disease resistance. While a number of sources for NO biosynthesis have been
      proposed, robust and biologically relevant routes for NO production largely
      remain to be defined. To elaborate cell death during an incompatible plant
      pathogen interaction NO functions in combination with reactive oxygen
      intermediates. Furthermore, NO has been shown to regulate the activity of
      metacaspases, evolutionary conserved proteases that may be intimately associated
      with pathogen-triggered cell death. NO is also thought to function in multiple
      modes of plant disease resistance by regulating, through S-nitrosylation,
      multiple nodes of the salicylic acid (SA) signalling pathway. These findings
      underscore the key role of NO in plant-pathogen interactions.

PMID- 18039743
TI  - New developments in the management of speech and language disorders.
AB  - Speech and language disorders, which include swallowing difficulties, are usually
      managed by speech and language therapists. Such a diverse, complex and
      challenging clinical group of symptoms requires practitioners with detailed
      knowledge and understanding of research within those areas, as well as the
      ability to implement appropriate therapy strategies within many environments.
      These environments range from neonatal units, acute paediatric wards and health
      centres through to nurseries, schools and children's homes. This paper summarises
      the key issues that are fundamental to our understanding of this client group.

PMID- 18039744
TI  - B cell depletion therapy for 19 patients with refractory systemic lupus
      erythematosus.
AB  - OBJECTIVE: B cell dysregulation is involved in the development of childhood-onset
      systemic lupus erythematosus (SLE). The safety and efficacy of B cell depletion
      therapy is evaluated in the the largest series of children to be presented in the
      literature. METHODS: 19 children (89% female) with SLE, aged 6-16 (median 14)
      years, treated with rituximab in a single centre were retrospectively reviewed.
      The British Isles Lupus Assessment Group (BILAG) index and biochemical,
      haematological and immunological parameters were evaluated before and after
      treatment, with the primary outcome assessed as normal results. Rituximab therapy
      was used for acute life- or organ-threatening symptoms or symptoms that had not
      responded to standard treatment. The range of symptoms included lupus nephritis,
      cerebral lupus and severe general symptoms. Rituximab 750 mg/m(2) was given
      intravenously twice, usually within a 2-week period. Patients were followed up
      for 6-38 (median 20) months. RESULTS: Rapid reduction of SLE disease activity was
      observed within the first month, represented by a reduction of BILAG scores (14
      to 6, p<0.005) and an improvement in renal function (estimated glomerular
      filtration rate of 54 to 68 ml/min/1.73 m(2), p = 0.07), immunological
      (complement C3: 0.46 to 0.83 g/l, p = 0.02) and haematological (haemoglobin: 9.7
      to 10.3 g/dl, p = 0.04) parameters. No serious side effects were observed, except
      for herpes zoster in five cases. CONCLUSION: In our cohort of children, rituximab
      was safe and effective when used in combination with standard immunosuppressive
      agents. Randomised controlled studies are needed to further evaluate the safety
      and efficacy of rituximab therapy.

PMID- 18039742
TI  - Three essential and conserved regions of the group II intron are proximal to the
      5'-splice site.
AB  - Despite the central role of group II introns in eukaryotic gene expression and
      their importance as biophysical and evolutionary model systems, group II intron
      tertiary structure is not well understood. In order to characterize the
      architectural organization of intron ai5gamma, we incorporated the photoreactive
      nucleotides s(4)U and s(6)dG at specific locations within the intron core and
      monitored the formation of cross-links in folded complexes. The resulting data
      reveal the locations for many of the most conserved, catalytically important
      regions of the intron (i.e., the J2/3 linker region, the IC1(i-ii) bulge in
      domain 1, the bulge of D5, and the 5'-splice site), showing that all of these
      elements are closely colocalized. In addition, we show by nucleotide analog
      interference mapping (NAIM) that a specific functional group in J2/3 plays a role
      in first-step catalysis, which is consistent with its apparent proximity to other
      first-step components. These results extend our understanding of active-site
      architecture during the first step of group II intron self-splicing and they
      provide a structural basis for spliceosomal comparison.

PMID- 18039745
TI  - Paediatric EEGs: what NICE didn't say.

PMID- 18039746
TI  - United Kingdom school-entry hearing screening: current practice.
AB  - OBJECTIVE: To determine if the school-entry hearing screening (SEHS) programme
      continues to make a useful contribution to the identification of childhood
      hearing impairment in the light of the recent implementation of universal newborn
      hearing screening, and thereby to inform future policy development. DESIGN:
      Postal questionnaire survey to determine current implementation and effectiveness
      of SEHS SETTING: 244 school health services managed within primary care and acute
      trusts throughout the UK. PARTICIPANTS: 229 SEHS service leads approached; 195
      responded. MAIN OUTCOME MEASURE: Details of implementation; positive predictive
      value of the screening test and its referral criteria. RESULTS: Implementation of
      the SEHS is variable, and there is no national approach to data collection, audit
      and quality assurance. Less than 10% of services had available robust data. The
      yield from screening ranges from 0.05% to 0.59% for permanent sensorineural
      hearing impairment and from 0.07% to 0.44% for permanent conductive hearing
      impairment. The positive predictive values from screen referral vary from 0.62%
      to 12.16% for permanent sensorineural hearing impairment and 1.24% to 17.56% for
      permanent conductive hearing impairment. CONCLUSION: This comprehensive survey
      provides a previously unavailable national examination of the SEHS. The few
      available data on yield indicate that the SEHS may have a small but important
      role to play in identification of childhood hearing impairment, but the
      overwhelming conclusion is the urgent need for national guidelines on
      implementation of this screening programme to determine its value since the
      implementation nationally of universal newborn hearing screening.

PMID- 18039747
TI  - Congenital cytomegalovirus: association between dried blood spot viral load and
      hearing loss.
AB  - AIM: To investigate the relation between cytomegalovirus (CMV) viral load on
      dried blood spots (DBS) from newborn biochemical screening ("Guthrie") cards, and
      sensorineural hearing loss (SNHL) in congenital CMV. DESIGN: Cross-sectional
      study with retrospective case-note review. SETTING: Seven paediatric audiology
      departments in the United Kingdom. PATIENTS: 84 children, median age 7 years: 43
      with known congenital CMV, 41 with unexplained SNHL. INTERVENTIONS: Half a DBS
      was tested for CMV DNA viral load by quantitative real-time polymerase chain
      reaction (PCR). MAIN OUTCOME MEASURES: Pure tone average hearing thresholds (0.5
      4 kHz). RESULTS: DBS CMV DNA viral load significantly correlated with hearing
      thresholds for the worse and better hearing ears (Spearman's rank correlations: r
      = 0.445, p = 0.008 and r = 0.481, p = 0.004 respectively). Multivariable logistic
      regression showed that the effect of DBS viral load on the risk of SNHL remained
      important, when age and central nervous system involvement had been taken into
      account (odds ratio (OR) 2.76, 95% confidence interval (CI) 1.14 to 6.63, p =
      0.024). The mean log DBS viral load was significantly higher in children with
      SNHL than in those with normal hearing (2.69 versus 1.64, 95% CI -1.84 to -0.27,
      p = 0.01). 8/35 (23%) children with unexplained SNHL tested positive for CMV DNA
      on DBS. One false positive result was obtained. CONCLUSION: The risk of SNHL
      increased with DBS viral load. Further studies should investigate whether DBS CMV
      testing has a role in identifying asymptomatic congenitally infected neonates at
      risk of SNHL, and whether antiviral treatment can reduce this risk.

PMID- 18039748
TI  - Ethical and legal aspects of video recording neonatal resuscitation.

PMID- 18039749
TI  - Assessing the effectiveness of two round neonatal resuscitation masks: study 1.
AB  - BACKGROUND: Positive pressure ventilation (PPV) via a face mask is an important
      skill taught using manikins. There have been few attempts to assess the
      effectiveness of different face mask designs. AIM: To determine whether leak at
      the face mask during simulated neonatal resuscitation differed between a new
      round mask design and the current most widely used model. METHOD: 50 participants
      gave PPV to a modified manikin designed to measure leak at the face mask. Leak
      was calculated from the difference between the inspired and expired tidal
      volumes. RESULTS: Mask leak varied widely with no significant difference between
      devices; mean (SD) percentage leak for the Laerdal round mask was 55% (31) and
      with the Fisher & Paykel mask it was 57% (25). CONCLUSION: We compared a new
      neonatal face mask with an established design and found no difference in leak. On
      average the mask leak was >50% irrespective of operator experience or technique.

PMID- 18039750
TI  - Improved techniques reduce face mask leak during simulated neonatal
      resuscitation: study 2.
AB  - BACKGROUND: Techniques of positioning and holding neonatal face masks vary.
      Studies have shown that leak at the face mask is common and often substantial
      irrespective of operator experience. AIMS: (1) To identify a technique for face
      mask placement and hold which will minimise mask leak. (2) To investigate the
      effect of written instruction and demonstration of the identified technique on
      mask leak for two round face masks. METHOD: Three experienced neonatologists
      compared methods of placing and holding face masks to minimise the leak for
      Fisher & Paykel 60 mm and Laerdal size 0/1 masks. 50 clinical staff gave positive
      pressure ventilation to a modified manikin designed to measure leak at the face
      mask. They were provided with written instructions on how to position and hold
      each mask and then received a demonstration. Face mask leak was measured after
      each teaching intervention. RESULTS: A technique of positioning and holding the
      face masks was identified which minimised leak. The mean (SD) mask leaks before
      instruction, after instruction and after demonstration were 55% (31), 49% (30),
      33% (26) for the Laerdal mask and 57% (25), 47% (28), 32% (30) for the Fisher &
      Paykel mask. There was no significant difference in mask leak between the two
      masks. Written instruction alone reduced leak by 8.8% (CI 1.4% to 16.2%) for
      either mask; when combined with a demonstration mask leak was reduced by 24.1%
      (CI 16.4% to 31.8%). CONCLUSION: Written instruction and demonstration of the
      identified optimal technique resulted in significantly reduced face mask leak.

PMID- 18039751
TI  - How do we spin wingspan?

PMID- 18039752
TI  - Perineural invasion through the maxillary division of the right trigeminal nerve
      in a rare case of nasolabial malignant peripheral nerve sheath tumor.
AB  - SUMMARY: We report the CT and MR imaging findings in a patient with malignant
      peripheral nerve sheath tumor in the right nasolabial area, which exhibited
      typical imaging features of cystic adenoid carcinoma.

PMID- 18039753
TI  - "Bovine" aortic arch.

PMID- 18039754
TI  - White matter abnormalities in mild traumatic brain injury: a diffusion tensor
      imaging study.
AB  - BACKGROUND AND PURPOSE: Traumatic axonal injury is a primary brain abnormality in
      head trauma and is characterized by reduction of fractional anisotropy (FA) on
      diffusion tensor imaging (DTI). Our hypothesis was that patients with mild
      traumatic brain injury (TBI) have widespread brain white matter regions of
      reduced FA involving a variety of fiber bundles and show fiber disruption on
      fiber tracking in a minority of these regions. MATERIALS AND METHODS: Ethics
      committee approval and informed consent were obtained. Twenty-one patients with
      mild TBI were investigated (men:women, 12:9; mean age +/- SD, 32 +/- 9 years). In
      a voxel-based comparison with 11 control subjects (men:women, 8:3; mean age, 37
      +/- 9 years) using z score analysis, patient regions with abnormally reduced FA
      were defined in brain white matter. MR imaging, DTI, and fiber tracking
      characteristics of these regions were described and analyzed using Pearson
      correlation, linear regression analysis, or the chi(2) test when appropriate.
      RESULTS: Patients had on average 9.1 regions with reduced FA, with a mean region
      volume of 525 mm(3), predominantly found in cerebral lobar white matter,
      cingulum, and corpus callosum. These regions mainly involved supratentorial
      projection fiber bundles, callosal fibers, and fronto-temporo-occipital
      association fiber bundles. Internal capsules and infratentorial white matter were
      relatively infrequently affected. Of all of the involved fiber bundles, 19.3%
      showed discontinuity on fiber tracking. CONCLUSION: Patients with mild TBI have
      multiple regions with reduced FA in various white matter locations and involving
      various fiber bundles. A minority of these fiber bundles show discontinuity on
      fiber tracking.

PMID- 18039755
TI  - Role of apparent diffusion coefficient values in differentiation between
      malignant and benign solitary thyroid nodules.
AB  - BACKGROUND AND PURPOSE: Accurate imaging characterization of a solitary thyroid
      nodule has been clearly problematic. The purpose of this study was to evaluate
      the role of the apparent diffusion coefficient (ADC) values in the
      differentiation between malignant and benign solitary thyroid nodules. MATERIALS
      AND METHODS: A prospective study was conducted in 67 consecutive patients with
      solitary thyroid nodules who underwent diffusion MR imaging of the thyroid gland.
      Diffusion-weighted MR images were acquired with b factors of 0, 250, and 500
      s/mm(2) by using single-shot echo-planar imaging. ADC maps were reconstructed.
      The ADC values of the solitary thyroid nodules were calculated and correlated
      with the results of histopathologic examination. Statistical analysis was
      performed. RESULTS: The mean ADC value of malignant solitary thyroid nodules was
      0.73 +/- 0.19 x 10(-3) mm(2)/s and of benign nodules was 1.8 +/- 0.27 x 10(-3)
      mm(2)/s. The mean ADC values of malignant nodules were significantly lower than
      those of benign ones (P = .0001). There were no significant differences between
      the mean ADC values of various malignant thyroid nodules, but there were
      significant differences between the subtypes of benign thyroid nodules (P =
      .0001). An ADC value of 0.98 x 10(-3) mm(2)/s was proved as a cutoff value
      differentiating between benign and malignant nodules, with 97.5%, 91.7%, and
      98.9% sensitivity, specificity, and accuracy, respectively. CONCLUSION: The ADC
      value is a new promising noninvasive imaging approach used for differentiating
      malignant from benign solitary thyroid nodules.

PMID- 18039756
TI  - A T1 hyperintense perilesional signal aids in the differentiation of a cavernous
      angioma from other hemorrhagic masses.
AB  - BACKGROUND AND PURPOSE: A cavernous angioma is a developmental vascular
      malformation with a high risk of hemorrhage. The purpose of this work was to
      retrospectively determine whether an MR sign of T1 hyperintense perilesional
      signal intensity is useful for the differentiation of cavernous angioma from
      other hemorrhagic cerebral masses. MATERIALS AND METHODS: The institutional
      review board approved this study. We retrospectively evaluated the MR images of
      72 patients with acute or subacute cerebral hemorrhagic lesions with perilesional
      edema (29 cavernous angiomas, 13 glioblastomas, 1 oligodendroglioma, 16
      metastatic tumors, and 13 intracerebral hemorrhages) for the presence of T1
      hyperintense perilesional signal intensity. In addition, T1 signal intensities of
      a perilesional edema were quantitatively analyzed. In cavernous angiomas, volumes
      of hemorrhagic lesions and perilesional edemas, lesion locations, presence of
      contrast enhancement, and time intervals between symptom onset and MR imaging
      were also assessed. Data were analyzed using unpaired t test or Fisher exact
      test. RESULTS: T1 hyperintense perilesional signal intensity sign was found in 18
      (62.1%) of 29 cavernous angiomas, in 1 (6.3%) of 16 metastases, and in 0 primary
      brain tumors or intracerebral hemorrhages. Sensitivity, specificity, and positive
      predictive value of this sign for cavernous angioma were 62%, 98%, and 95%,
      respectively. The perilesional T1 hyperintensity was significantly higher in
      cavernous angiomas (P = .045) than in normal white matter. Perilesional edema
      volumes were larger in cavernous angiomas with the MR sign than in cavernous
      angiomas without the sign (P = .009). CONCLUSION: When the MR sign of T1
      hyperintense perilesional signal intensity is present, there is a high
      probability of cavernous angioma being present in the brain, and this MR sign may
      be helpful for differentiating cavernous angioma from hemorrhagic tumors and
      intracerebral hemorrhages.

PMID- 18039757
TI  - Language dysfunction after stroke and damage to white matter tracts evaluated
      using diffusion tensor imaging.
AB  - BACKGROUND AND PURPOSE: Knowledge of the anatomic basis of aphasia after stroke
      has both theoretic and clinical implications by informing models of cortical
      connectivity and providing data for diagnosis and prognosis. In this study we use
      diffusion tensor imaging to address the relationship between damage to specific
      white matter tracts and linguistic deficits after left hemisphere stroke.
      MATERIALS AND METHODS: Twenty patients aged 38-77 years with a history of stroke
      in the left hemisphere underwent diffusion tensor imaging, structural MR imaging,
      and language testing. All of the patients were premorbidly right handed and
      underwent imaging and language testing at least 1 month after stroke. RESULTS:
      Lower fractional anisotropy (FA) values in the superior longitudinal and arcuate
      fasciculi of the left hemisphere, an indication of greater damage to these
      tracts, were correlated with decreased ability to repeat spoken language.
      Comprehension deficits after stroke were associated with lower FA values in the
      arcuate fasciculus of the left hemisphere. The findings for repetition were
      independent of MR imaging ratings of the degree of damage to cortical areas of
      the left hemisphere involved in language function. There were no findings for
      homotopic tracts in the right hemisphere. CONCLUSION: This study provides support
      for a specific role for damage to the superior longitudinal and arcuate fasciculi
      in the left hemisphere in patients with deficits in repetition of speech in
      aphasia after stroke.

PMID- 18039758
TI  - Contrast enhancement hyperdensity after endovascular coiling of intracranial
      aneurysms.
AB  - BACKGROUND AND PURPOSE: Endovascular coil embolization is used increasingly to
      treat cerebral aneurysms. The purpose of our study was to quantify the incidence
      of CT-detectable abnormalities after aneurysm coiling and map the radiographic
      and clinical progression. MATERIALS AND METHODS: We reviewed the radiographic and
      clinical sequelae of 30 consecutive patients with aneurysms who underwent
      endosaccular coiling followed by head CT scans. Patients with CT abnormalities
      received follow-up scans at 4 to 6 hours and 20 to 25 hours. Contrast enhancement
      was defined as CT hyperdensities with progressive resolution over 25 hours and a
      Hounsfield unit (HU) of less than 70. The incidence of CT abnormalities was
      recorded and correlated with amount of contrast used, use of antiplatelet agents,
      procedure time, and clinical sequelae. RESULTS: Seven patients (23%) had new
      hyperdensities on CT scan. Four showed gyral hyperattenuation; 1 showed basal
      ganglia hyperattenuation, and 2 showed a combination of these patterns. All were
      asymptomatic and were consistent with contrast enhancement, with complete
      resolution in 5 of 7 and partial resolution in 2 of 7 by 20 to 25 hours.
      Antithrombotic or antiplatelet medication was continued in all cases. The amount
      of contrast used (P = .014) and the use of antiplatelet medication (P = .029)
      were statistically correlated with the presence of hyperattenuation after
      aneurysm coiling, whereas the length of the procedure was not (P = .162).
      CONCLUSION: Contrast enhancement, unlike contrast extravasation, is a fairly
      common and clinically benign finding after aneurysm coiling. The enhancement
      resolves by 25 hours in most cases, regardless of the continuation of
      antithrombotic or antiplatelet therapy.

PMID- 18039759
TI  - Shoppers Drug Mart or poachers drug mart?

PMID- 18039760
TI  - Expression of a uniquely regulated extracellular polysaccharide confers a large
      capsule phenotype to Bacteroides fragilis.
AB  - Bacteroides fragilis synthesizes eight distinct capsular polysaccharides, more
      than any described bacterium outside the order Bacteroidales. Here, we show that
      this organism also produces a high-molecular-weight extracellular polysaccharide
      (EPS). Expression of the EPS results in the formation of a large polysaccharide
      layer around the bacteria which prevents them from forming a tight pellet upon
      centrifugation and from entering a Percoll density gradient. Like expression of
      the capsular polysaccharides, expression of the EPS is phase variable and
      dictated by DNA inversion of its promoter. EPS expression is regulated at one
      level by the DNA invertase Tsr19, which is encoded by a gene immediately upstream
      of the EPS locus and inverts the EPS promoter, causing an on or off phenotype.
      Expression of the EPS is also regulated at another level, which dictates the
      amount of EPS produced. By analyzing a panel of tsr19 deletion mutants, we found
      that the number of inverted repeats (IRs) flanking the promoter is variable.
      Transcription into the EPS genes is greater in mutants with a single IR between
      the promoter and the downstream EPS genes than in mutants with more than one IR
      in this region, correlating with the synthesis of more EPS. By analyzing the
      relative orientations of the EPS promoter of bacteria obtained from human fecal
      samples, we showed that both DNA inversion and variation in the number of IRs are
      active processes of B. fragilis in the endogenous human intestinal ecosystem.

PMID- 18039761
TI  - An AbrB-Like protein regulates the expression of the bidirectional hydrogenase in
      Synechocystis sp. strain PCC 6803.
AB  - In the unicellular cyanobacterium Synechocystis sp. strain PCC 6803, the
      pentameric bidirectional Ni-Fe hydrogenase (HoxEFUYH) is the sole enzyme involved
      in hydrogen metabolism. Recent investigations implicated the transcription factor
      LexA in the regulation of the hox genes in this cyanobacterium, suggesting the
      factor to work as an activator. In this work, we show evidence that LexA cannot
      account exclusively for the regulation of the hox genes in this cyanobacterium.
      Therefore, we investigated which additional transcription factors interact in and
      may regulate the expression of the hox genes in Synechocystis sp. strain PCC
      6803. By using DNA affinity assays, a transcription factor with similarity to the
      transition state regulator AbrB from Bacillus subtilis was isolated.
      Electrophoretic mobility shift assays showed that the AbrB-like protein
      specifically interacts with the promoter region of the hox genes as well as with
      its own promoter region. In addition, results obtained with two genetically
      modified strains of Synechocystis sp. strain PCC 6803, one with a not fully
      segregated inactivation mutation of the abrB-like gene and the other
      overexpressing the same abrB-like gene, suggest that this transcription factor
      functions as a regulator of hox gene expression.

PMID- 18039762
TI  - Natural variability in S-adenosylmethionine (SAM)-dependent riboswitches: S-box
      elements in bacillus subtilis exhibit differential sensitivity to SAM In vivo and
      in vitro.
AB  - Riboswitches are regulatory systems in which changes in structural elements in
      the 5' region of the nascent RNA transcript (the "leader region") control
      expression of the downstream coding sequence in response to a regulatory signal
      in the absence of a trans-acting protein factor. The S-box riboswitch, found
      primarily in low-G+C gram-positive bacteria, is the paradigm for riboswitches
      that sense S-adenosylmethionine (SAM). Genes in the S-box family are involved in
      methionine metabolism, and their expression is induced in response to starvation
      for methionine. S-box genes exhibit conserved primary sequence and secondary
      structural elements in their leader regions. We previously demonstrated that SAM
      binds directly to S-box leader RNA, causing a structural rearrangement that
      results in premature termination of transcription at S-box leader region
      terminators. S-box genes have a variety of physiological roles, and natural
      variability in S-box structure and regulatory response could provide additional
      insight into the role of conserved S-box leader elements in SAM-directed
      transcription termination. In the current study, in vivo and in vitro assays were
      employed to analyze the differential regulation of S-box genes in response to
      SAM. A wide range of responses to SAM were observed for the 11 S-box-regulated
      transcriptional units in Bacillus subtilis, demonstrating that S-box riboswitches
      can be calibrated to different physiological requirements.

PMID- 18039763
TI  - Study of anoxic and oxic cholesterol metabolism by Sterolibacterium
      denitrificans.
AB  - The initial enzymes and genes involved in the anoxic metabolism of cholesterol
      were studied in the denitrifying bacterium Sterolibacterium denitrificans Chol
      1S(T). The second enzyme of the proposed pathway, cholest-4-en-3-one-Delta1
      dehydrogenase (AcmB), was partially purified. Based on amino acid sequence
      analysis, a gene probe was derived to screen a cosmid library of chromosomal DNA
      for the acmB gene. A positive clone comprising a 43-kbp DNA insert was sequenced.
      In addition to the acmB gene, the DNA fragment harbored the acmA gene, which
      encodes the first enzyme of the pathway, cholesterol dehydrogenase/isomerase. The
      acmA gene was overexpressed, and the recombinant dehydrogenase/isomerase was
      purified. This enzyme catalyzes the predicted transformation of cholesterol to
      cholest-4-en-3-one. S. denitrificans cells grown aerobically with cholesterol
      exhibited the same pattern of soluble proteins and cell extracts formed the same
      14C-labeled products from [14C]cholesterol as cells that were grown under anoxic,
      denitrifying conditions. This is especially remarkable for the late products that
      are formed by anaerobic hydroxylation of the cholesterol side chain with water as
      the oxygen donor. Hence, this facultative anaerobic bacterium may use the anoxic
      pathway lacking any oxygenase-dependent reaction also under oxic conditions. This
      confers metabolic flexibility to such facultative anaerobic bacteria.

PMID- 18039764
TI  - Energy conservation via electron-transferring flavoprotein in anaerobic bacteria.

PMID- 18039765
TI  - Existence of abnormal protein aggregates in healthy Escherichia coli cells.
AB  - Protein aggregation is a phenomenon observed in all organisms and has often been
      linked with cell disorders. In addition, several groups have reported a virtual
      absence of protein aggregates in healthy cells. In contrast to previous studies
      and the expected outcome, we observed aggregated proteins in aerobic
      exponentially growing and "healthy" Escherichia coli cells. We observed
      overrepresentation of "aberrant proteins," as well as substrates of the major
      conserved chaperone DnaK (Hsp70) and the protease ClpXP (a serine protease), in
      the aggregates. In addition, the protein aggregates appeared to interact with
      chaperones known to be involved in the aggregate repair pathway, including ClpB,
      GroEL, GroES, and DnaK. Finally, we showed that the levels of reactive oxygen
      species and unfolded or misfolded proteins determine the levels of protein
      aggregates. Our results led us to speculate that protein aggregates may function
      as a temporary "trash organelle" for cellular detoxification.

PMID- 18039767
TI  - Structural basis for different substrate specificities of two ADP-ribose
      pyrophosphatases from Thermus thermophilus HB8.
AB  - ADP-ribose (ADPR) is one of the main substrates of Nudix proteins. Among the
      eight Nudix proteins of Thermus thermophilus HB8, we previously determined the
      crystal structure of Ndx4, an ADPR pyrophosphatase (ADPRase). In this study we
      show that Ndx2 of T. thermophilus also preferentially hydrolyzes ADPR and flavin
      adenine dinucleotide and have determined its crystal structure. We have
      determined the structures of Ndx2 alone and in complex with Mg2+, with Mg2+ and
      AMP, and with Mg2+ and a nonhydrolyzable ADPR analogue. Although Ndx2 recognizes
      the AMP moiety in a manner similar to those for other ADPRases, it recognizes the
      terminal ribose in a distinct manner. The residues responsible for the
      recognition of the substrate in Ndx2 are not conserved among ADPRases. This may
      reflect the diversity in substrate specificity among ADPRases. Based on these
      results, we propose the classification of ADPRases into two types: ADPRase-I
      enzymes, which exhibit high specificity for ADPR; and ADPRase-II enzymes, which
      exhibit low specificity for ADPR. In the active site of the ternary complexes,
      three Mg2+ ions are coordinated to the side chains of conserved glutamate
      residues and water molecules. Substitution of Glu90 and Glu94 with glutamine
      suggests that these residues are essential for catalysis. These results suggest
      that ADPRase-I and ADPRase-II enzymes have nearly identical catalytic mechanisms
      but different mechanisms of substrate recognition.

PMID- 18039766
TI  - Transcription profiling of the stringent response in Escherichia coli.
AB  - The bacterial stringent response serves as a paradigm for understanding global
      regulatory processes. It can be triggered by nutrient downshifts or starvation
      and is characterized by a rapid RelA-dependent increase in the alarmone (p)ppGpp.
      One hallmark of the response is the switch from maximum-growth-promoting to
      biosynthesis-related gene expression. However, the global transcription patterns
      accompanying the stringent response in Escherichia coli have not been analyzed
      comprehensively. Here, we present a time series of gene expression profiles for
      two serine hydroxymate-treated cultures: (i) MG1655, a wild-type E. coli K-12
      strain, and (ii) an isogenic relADelta251 derivative defective in the stringent
      response. The stringent response in MG1655 develops in a hierarchical manner,
      ultimately involving almost 500 differentially expressed genes, while the
      relADelta251 mutant response is both delayed and limited in scope. We show that
      in addition to the down-regulation of stable RNA-encoding genes, flagellar and
      chemotaxis gene expression is also under stringent control. Reduced transcription
      of these systems, as well as metabolic and transporter-encoding genes,
      constitutes much of the down-regulated expression pattern. Conversely, a
      significantly larger number of genes are up-regulated. Under the conditions used,
      induction of amino acid biosynthetic genes is limited to the leader sequences of
      attenuator-regulated operons. Instead, up-regulated genes with known functions,
      including both regulators (e.g., rpoE, rpoH, and rpoS) and effectors, are largely
      involved in stress responses. However, one-half of the up-regulated genes have
      unknown functions. How these results are correlated with the various effects of
      (p)ppGpp (in particular, RNA polymerase redistribution) is discussed.

PMID- 18039768
TI  - Role of stress response sigma factor SigG in Mycobacterium tuberculosis.
AB  - The sigG gene of Mycobacterium tuberculosis was disrupted by homologous
      recombination, and the genes regulated by SigG were examined by real-time reverse
      transcription PCR and microarray studies. The SigG consensus promoter recognition
      sequence was identified as GCGNGT-N15-18-CGANCA. A DeltasigG mutant was found to
      be more resistant to mitomycin C treatment than the wild-type strain, indicating
      that it may be involved in the SOS response in M. tuberculosis.

PMID- 18039769
TI  - Modulation of horizontally acquired genes by the Hha-YdgT proteins in Salmonella
      enterica serovar Typhimurium.
AB  - We describe a transcriptomic study of the effect of hha and ydgT mutations in
      Salmonella enterica serovar Typhimurium. A large number of genes showing altered
      expression are located in AT-rich horizontally acquired DNA sequences. Many of
      these genes have also been reported to be targets for H-NS. As Hha and YdgT
      interact with H-NS, our findings strongly suggest that Hha and/or YdgT must form
      complexes with H-NS when they silence these DNA regions.

PMID- 18039770
TI  - ExoS controls the cell contact-mediated switch to effector secretion in
      Pseudomonas aeruginosa.
AB  - Type III secretion is used by many gram-negative bacterial pathogens to directly
      deliver protein toxins (effectors) into targeted host cells. In all cases,
      secretion of effectors is triggered by host cell contact, although the mechanism
      is unclear. In Pseudomonas aeruginosa, expression of all type III secretion
      related genes is up-regulated when secretion is triggered. We were able to
      visualize this process using a green fluorescent protein reporter system and to
      use it to monitor the ability of bacteria to trigger effector secretion on cell
      contact. Surprisingly, the action of one of the major type III secreted
      effectors, ExoS, prevented triggering of type III secretion by bacteria that
      subsequently attached to cells, suggesting that triggering of secretion is
      feedback regulated. Evidence is presented that translocation (secretion of
      effectors across the host cell plasma membrane) of ExoS is indeed self-regulated
      and that this inhibition of translocation can be achieved by either of its two
      enzymatic activities. The translocator proteins PopB, PopD, and PcrV are secreted
      via the type III secretion system and are required for pore formation and
      translocation of effectors across the host cell plasma membrane. Here we present
      data that secretion of translocators is in fact not controlled by calcium,
      implying that triggering of effector secretion on cell contact represents a
      switch in secretion specificity, rather than a triggering of secretion per se.
      The requirement for a host cell cofactor to control effector secretion may help
      explain the recently observed phenomenon of target cell specificity in both the
      Yersinia and P. aeruginosa type III secretion systems.

PMID- 18039771
TI  - Identification of a spermidine excretion protein complex (MdtJI) in Escherichia
      coli.
AB  - A spermidine excretion protein in Escherichia coli was looked for among 33
      putative drug exporters thus far identified. Cell toxicity and inhibition of
      growth due to overaccumulation of spermidine were examined in an E. coli strain
      deficient in spermidine acetyltransferase, an enzyme that metabolizes spermidine.
      Toxicity and inhibition of cell growth by spermidine were recovered in cells
      transformed with pUCmdtJI or pMWmdtJI, encoding MdtJ and MdtI, which belong to
      the small multidrug resistance family of drug exporters. Both mdtJ and mdtI are
      necessary for recovery from the toxicity of overaccumulated spermidine. It was
      also found that the level of mdtJI mRNA was increased by spermidine. The
      spermidine content in cells cultured in the presence of 2 mM spermidine was
      decreased, and excretion of spermidine from cells was enhanced by MdtJI,
      indicating that the MdtJI complex can catalyze excretion of spermidine from
      cells. It was found that Tyr4, Trp5, Glu15, Tyr45, Tyr61, and Glu82 in MdtJ and
      Glu5, Glu19, Asp60, Trp68, and Trp81 in MdtI are involved in the excretion
      activity of MdtJI.

PMID- 18039772
TI  - Regulation of L-lactate utilization by the FadR-type regulator LldR of
      Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum can grow on L-lactate as a sole carbon and energy
      source. The NCgl2816-lldD operon encoding a putative transporter (NCgl2816) and a
      quinone-dependent L-lactate dehydrogenase (LldD) is required for L-lactate
      utilization. DNA affinity chromatography revealed that the FadR-type regulator
      LldR (encoded by NCgl2814) binds to the upstream region of NCgl2816-lldD.
      Overexpression of lldR resulted in strongly reduced NCgl2816-lldD mRNA levels and
      strongly reduced LldD activity, and as a consequence, a severe growth defect was
      observed in cells grown on L-lactate as the sole carbon and energy source, but
      not in cells grown on glucose, ribose, or acetate. Deletion of lldR had no effect
      on growth on these carbon sources but resulted in high NCgl2816-lldD mRNA levels
      and high LldD activity in the presence and absence of L-lactate. Purified His
      tagged LldR bound to a 54-bp fragment of the NCgl2816-lldD promoter, which
      overlaps with the transcriptional start site determined by random amplification
      of cDNA ends-PCR and contains a putative operator motif typical of FadR-type
      regulators, which is -1TNGTNNNACNA10. Mutational analysis revealed that this
      motif with hyphenated dyad symmetry is essential for binding of LldD to the
      NCgl2816-lldD promoter. L-Lactate, but not D-lactate, interfered with binding of
      LldRHis to the NCgl2816-lldD promoter. Thus, during growth on media lacking L
      lactate, LldR represses expression of NCgl2816-lldD. In the presence of L-lactate
      in the growth medium or under conditions leading to intracellular L-lactate
      accumulation, the L-lactate utilization operon is induced.

PMID- 18039773
TI  - Serotonin 5-HT2C receptor agonist promotes hypophagia via downstream activation
      of melanocortin 4 receptors.
AB  - The neurotransmitter serotonin (5-hydroxytryptamine) is a well-established
      modulator of energy balance. Both pharmacological and genetic evidence implicate
      the serotonin 2C receptor (5-HT(2C)R) as a critical receptor mediator of
      serotonin's effects on ingestive behavior. Here we characterized the effect of
      the novel and selective 5-HT(2C)R agonist BVT.X on energy balance in obese and
      lean mice and report that BVT.X significantly reduces acute food intake without
      altering locomotor activity or oxygen consumption. In an effort to elucidate the
      mechanism of this effect, we examined the chemical phenotype of 5-HT(2C)R
      expressing neurons in a critical brain region affecting feeding behavior, the
      arcuate nucleus of the hypothalamus. We show that 5-HT(2C)Rs are coexpressed with
      neurons containing proopiomelanocortin, known to potently affect appetite, in the
      arcuate nucleus of the hypothalamus of the mouse. We then demonstrate that
      prolonged infusion with BVT.X in obese mice significantly increases Pomc mRNA and
      reduces body weight, percent body fat, and initial food intake. To evaluate the
      functional importance of melanocortin circuitry in the effect of BVT.X on
      ingestive behavior, we assessed mice with disrupted melanocortin pathways. We
      report that mice lacking the melanocortin 4 receptor are not responsive to BVT.X
      induced hypophagia, demonstrating that melanocortins acting on melanocortin 4
      receptor are a requisite downstream pathway for 5-HT(2C)R agonists to exert
      effects on food intake. The data presented here not only indicate that the novel
      5-HT(2C)R agonist BVT.X warrants further investigation as a treatment for obesity
      but also elucidate specific neuronal pathways potently affecting energy balance
      through which 5-HT(2C)R agonists regulate ingestive behavior.

PMID- 18039774
TI  - Factors contributing to obesity in bombesin receptor subtype-3-deficient mice.
AB  - Mice with a targeted disruption of bombesin receptor subtype-3 (BRS-3 KO) develop
      hyperphagia, obesity, hypertension, and impaired glucose metabolism. However, the
      factors contributing to their phenotype have not been clearly established. To
      determine whether their obesity is a result of increased food intake or a defect
      in energy regulation, we matched the caloric intake of BRS-3 KO mice to wild-type
      (WT) ad libitum (ad lib)-fed controls over 21 wk. Although BRS-3 KO ad lib-fed
      mice were 29% heavier, the body weights of BRS-3 KO pair-fed mice did not differ
      from WT ad lib-fed mice. Pair-feeding BRS-3 KO mice normalized plasma insulin but
      failed to completely reverse increased adiposity and leptin levels. Hyperphagia
      in ad lib-fed KO mice was due to an increase in meal size without a compensatory
      decrease in meal frequency resulting in an increase in total daily food intake.
      An examination of neuropeptide Y, proopiomelanocortin, and agouti-related peptide
      gene expression in the arcuate nucleus revealed that BRS-3 KO mice have some
      deficits in their response to energy regulatory signals. An evaluation of the
      satiety effects of cholecystokinin, bombesin, and gastrin-releasing peptide found
      no differences in feeding suppression by these peptides. We conclude that
      hyperphagia is a major factor leading to increased body weight and
      hyperinsulinemia in BRS-3 KO mice. However, our finding that pair-feeding did not
      completely normalize fat distribution and plasma leptin levels suggests there is
      also a metabolic dysregulation that may contribute to, or sustain, their obese
      phenotype.

PMID- 18039775
TI  - Estrogens promote human testicular germ cell cancer through a membrane-mediated
      activation of extracellular regulated kinase and protein kinase A.
AB  - Clinical and experimental studies have suggested that estrogens, the archetype of
      female hormones, participate in the control of male germ cell proliferation and
      that fetal exposure to environmental estrogens may contribute to hypofertility
      and/or to testicular germ cell cancer. However, the underlying mechanisms remain
      to be elucidated. 17beta-Estradiol (E2) conjugated to BSA was able to stimulate
      human testicular seminoma cell proliferation by triggering a rapid, nongenomic,
      membrane-mediated activation of ERK1/2 and cAMP-dependent protein kinase A (PKA).
      Both ERK1/2 and PKA participated in this promoting effect. This activation was
      associated with phosphorylation of the transcription factor cAMP response element
      binding protein and the nuclear factor retinoblastoma protein. Enhanced
      proliferation together with ERK activation could be reversed by pertussis toxin,
      a G protein inhibitor. Estrogen receptors (ERs) in JKT-1 were characterized by
      immunofluorescence, subcellular fractioning, and Western blot. JKT-1 cells did
      not express ERalpha but ERbeta, which localized to the mitochondria and the
      nucleus but not to the membrane. Moreover, neither ICI-182,780, a classical ER
      antagonist, nor tamoxifen, a selective ER modulator, could reverse the 17beta
      estradiol-BSA-induced promoting effect. Estrogens contribute to human testicular
      germ cell cancer proliferation by rapid activation of ERK1/2 and PKA through a
      membrane nonclassical ER. This nongenomic effect represents a new basis for
      understanding the estrogenic control of spermatogenesis and evaluating the role
      of fetal exposure to xenoestrogens during malignant transformation of testicular
      germ stem cells.

PMID- 18039776
TI  - The murine glucagon-like peptide-1 receptor is essential for control of bone
      resorption.
AB  - Gastrointestinal hormones including gastric inhibitory polypeptide (GIP),
      glucagon-like peptide (GLP)-1, and GLP-2 are secreted immediately after meal
      ingestion, and GIP and GLP-2 have been shown to regulate bone turnover. We
      hypothesize that endogenous GLP-1 may also be important for control of skeletal
      homeostasis. We investigated the role of GLP-1 in the regulation of bone
      metabolism using GLP-1 receptor knockout (Glp-1r(-/-)) mice. A combination of
      bone density and histomorphometry, osteoclast activation studies, biochemical
      analysis of calcium and PTH, and RNA analysis was used to characterize bone and
      mineral homeostasis in Glp-1r(-/-) and Glp-1r(+/+) littermate controls. Glp-1r(-/
      ) mice have cortical osteopenia and bone fragility by bone densitometry as well
      as increased osteoclastic numbers and bone resorption activity by bone
      histomorphometry. Although GLP-1 had no direct effect on osteoclasts and
      osteoblasts, Glp-1r(-/-) mice exhibited higher levels of urinary
      deoxypyridinoline, a marker of bone resorption, and reduced levels of calcitonin
      mRNA transcripts in the thyroid. Moreover, calcitonin treatment effectively
      suppressed urinary levels of deoxypyridinoline in Glp-1r(-/-), mice and the GLP-1
      receptor agonist exendin-4 increased calcitonin gene expression in the thyroid of
      wild-type mice. These findings establish an essential role for endogenous GLP-1
      receptor signaling in the control of bone resorption, likely through a calcitonin
      dependent pathway.

PMID- 18039777
TI  - Preimplantation embryos cooperate with oviductal cells to produce embryotrophic
      inactivated complement-3b.
AB  - Human oviductal epithelial (OE) cells produce complement protein 3 (C3) and its
      derivatives, C3b and inactivated complement-3b (iC3b). Among them, iC3b is the
      most potent embryotrophic molecule. We studied the production of iC3b in the
      oviductal cell/embryo culture system. In the immune system, C3 convertase
      converts C3 into C3b, and the conversion of C3b to iC3b requires factor I (fI)
      and its cofactors, such as factor H or membrane cofactor protein. Human oviductal
      epithelium and OE cells expressed mRNA and protein of the components of C3
      convertase, including C2, C4, factor B, and factor D. The OE cell-conditioned
      medium contained active C3 convertase activity that was suppressed by C3
      convertase inhibitor, H17 in a dose and time-dependent manner. Although the
      oviductal epithelium and OE cells produced fI, the production of its cofactor,
      factor H required for the conversion of C3b to iC3b, was weak. Thus, OE cell
      conditioned medium was inefficient in producing iC3b from exogenous C3b. On the
      contrary, mouse embryos facilitated such conversion to iC3b, which was taken up
      by the embryos, resulting in the formation of more blastocysts of larger size.
      The facilitatory activity was mediated by complement receptor 1-related
      gene/protein Y (Crry) with known membrane cofactor protein activity on the
      trophectoderm of the embryos as anti-Crry antibody inhibited the conversion and
      embryotrophic activity of C3b in the presence of fI. In conclusion, human oviduct
      possesses C3 convertase activity converting C3 to C3b, and Crry of the
      preimplantation embryos may be involved in the production of embryotrophic iC3b
      on the surface of the embryos.

PMID- 18039778
TI  - One-cell zygote transfer from diabetic to nondiabetic mouse results in congenital
      malformations and growth retardation in offspring.
AB  - Fetuses of type 1 and 2 diabetic women experience higher incidences of
      malformations and fetal death as compared with nondiabetics, even when they
      achieve adequate glycemic control during the first trimester. We hypothesize that
      maternal diabetes adversely affects the earliest embryonic stage after
      fertilization and programs the fetus to experience these complications. To test
      this hypothesis, we transferred either one-cell mouse zygotes or blastocysts from
      either streptozotocin-induced diabetic or control mice into nondiabetic
      pseudopregnant female recipients. We then evaluated the fetuses at embryonic d
      14.5 to assess fetal growth and the presence or absence of malformations. We
      found that fetuses from the diabetic mice transferred at the blastocyst stage but
      also as early as the one-cell zygote stage displayed significantly higher rates
      of malformations consistent with neural tube closure problems and abdominal wall
      and limb deformities. In addition, both these groups of fetuses were
      significantly growth retarded. To determine if this phenomenon was due to high
      glucose concentrations, two-cell embryos were cultured to a blastocyst stage in
      52 mm D-glucose or L-glucose as an osmotic control, transferred into nondiabetic
      pseudopregnant mice, and examined at embryonic d 14.5. These embryos did not
      demonstrate any evidence of malformations, however, they did experience
      significantly higher rates of resorptions, lower implantation rates, and they
      were significantly smaller at embryonic d 14.5. In summary, exposure to maternal
      diabetes during oogenesis, fertilization, and the first 24 h was enough to
      program permanently the fetus to develop significant morphological changes.

PMID- 18039779
TI  - Cyclooxygenase-2 regulates survival, migration, and invasion of human
      endometriotic cells through multiple mechanisms.
AB  - Endometriosis is a debilitating disease characterized by the presence of
      functional endometrial glandular epithelium and stroma outside the uterine cavity
      that affects up to 20% of women of child-bearing age. Cyclooxygenase-2 (COX-2), a
      rate-limiting enzyme in the biosynthesis of prostaglandin E(2) (PGE(2)), is
      highly expressed in endometriotic tissues and results in increased concentrations
      of peritoneal PGE(2) in women. In this study, we determined the expression of COX
      2 protein in ectopic and eutopic endometria in humans and the role of COX-2 in
      endometriotic cell survival, migration, and invasion in humans. Our results
      indicate that COX-2 protein is abundantly expressed in ectopic endometria
      compared with eutopic endometria. Comparatively, expression of COX-2 protein is
      higher in eutopic endometria from women with endometriosis compared with women
      without endometriosis. Inhibition of COX-2 decreases survival, migration, and
      invasion of endometriotic cells that are associated with decreased production of
      PGE(2). Cell growth inhibitory effects of COX-2 inhibition/silencing are mediated
      through nuclear poly (ADP-ribose) polymerase-mediated apoptosis. Cell motility
      and invasion inhibitory effects of COX-2 inhibition/silencing are mediated
      through matrix metalloproteinase-2 and -9 activities. Interestingly, effects of
      COX-2 inhibition is more profound in endometriotic epithelial than in stromal
      cells. Furthermore, inhibition of COX-2 affects invasion rather than migration of
      endometriotic epithelial and stromal cells. It is the first evidence showing that
      inhibition of COX-2 decreases endometriotic epithelial and stromal cell survival,
      migration, and invasion in humans. Our results support the emerging concept that
      COX-2/PGE(2) promotes the pathophysiology and pathogenesis of endometriosis in
      humans.

PMID- 18039780
TI  - Mammalian type I gonadotropin-releasing hormone receptors undergo slow,
      constitutive, agonist-independent internalization.
AB  - Regulatory elements present in the cytoplasmic carboxyl-terminal tails of G
      protein-coupled receptors contribute to agonist-dependent receptor
      desensitization, internalization, and association with accessory proteins such as
      beta-arrestin. The mammalian type I GnRH receptors are unique among the rhodopsin
      like G protein-coupled receptors because they lack a cytoplasmic carboxyl
      terminal tail. In addition, they do not recruit beta-arrestin, nor do they
      undergo rapid desensitization. By measuring the internalization of labeled GnRH
      agonists, previous studies have reported that mammalian type I GnRH receptors
      undergo slow agonist-dependent internalization. In the present study, we have
      measured the internalization of epitope-tagged GnRH receptors, both in the
      absence and presence of GnRH stimulation. We demonstrate that mammalian type I
      GnRH receptors exhibit a low level of constitutive agonist-independent
      internalization. Stimulation with GnRH agonist did not significantly enhance the
      level of receptor internalization above the constitutive level. In contrast, the
      catfish GnRH and rat TRH receptors, which have cytoplasmic carboxyl-terminal
      tails, displayed similar levels of constitutive agonist-independent
      internalization but underwent robust agonist-dependent internalization, as did
      chimeras of the mammalian type I GnRH receptor with the cytoplasmic carboxyl
      terminal tails of the catfish GnRH receptor or the rat TRH receptor. When the
      carboxyl-terminal Tyr325 and Leu328 residues of the mammalian type I GnRH
      receptor were replaced with alanines, these two mutant receptors underwent
      significantly impaired internalization, suggesting a function for the Tyr-X-X-Leu
      sequence in mediating the constitutive agonist-independent internalization of
      mammalian type I GnRH receptors. These findings provide further support for the
      underlying notion that the absence of the cytoplasmic carboxyl-terminal tail of
      the mammalian type I GnRH receptors has been selected for during evolution to
      prevent rapid receptor desensitization and internalization to allow protracted
      GnRH signaling in mammals.

PMID- 18039781
TI  - Oxytocin facilitates female sexual maturation through a glia-to-neuron signaling
      pathway.
AB  - It has been earlier proposed that oxytocin could play a facilitatory role in the
      preovulatory LH surge in both rats and humans. We here provide evidence that
      oxytocin also facilitates sexual maturation in female rats. The administration of
      an oxytocin antagonist for 6 d to immature female rats decreased GnRH pulse
      frequency ex vivo and delayed the age at vaginal opening and first estrus. The in
      vitro reduction in GnRH pulse frequency required chronic blockade of oxytocin
      receptors, because it was not acutely observed after a single injection of the
      antagonist. Hypothalamic explants exposed to the antagonist in vitro showed a
      reduced GnRH pulse frequency and failed to respond to oxytocin with GnRH release.
      Prostaglandin E(2) (PGE(2)) mimicked the stimulatory effect of oxytocin on GnRH
      pulse frequency, and inhibition of PG synthesis blocked the effect of oxytocin,
      suggesting that oxytocin accelerates pulsatile GnRH release via PGE(2). The
      source of PGE(2) appears to be astrocytes, because oxytocin stimulates PGE(2)
      release from cultured hypothalamic astrocytes. Moreover, astrocytes express
      oxytocin receptors, whereas GnRH neurons do not. These results suggest that
      oxytocin facilitates female sexual development and that this effect is mediated
      by a mechanism involving glial production of PGE(2).

PMID- 18039783
TI  - Rhythmic expression of functional MT1 melatonin receptors in the rat adrenal
      gland.
AB  - We previously demonstrated that melatonin is involved in the regulation of
      adrenal glucocorticoid production in diurnal primates through activation of MT1
      membrane-bound melatonin receptors. However, whether melatonin has a similar role
      in nocturnal rodents remains unclear. Using an integrative approach, here we show
      that the adult rat adrenal gland expresses a functional MT1 melatonin receptor in
      a rhythmic fashion. We found that: 1) expression of the cognate mRNA encoding for
      the MT1 membrane-bound melatonin receptor, displaying higher levels in the
      day/night transition (1800-2200 h); 2) expression of the predicted 37-kDa MT1
      polypeptide in immunoblots from adrenals collected at 2200 h but not 1000 h; 3)
      no expression of the MT2 melatonin receptor mRNA and protein; 4) specific high
      affinity 2-[(125)I]iodomelatonin binding in membrane fractions and frozen
      sections from adrenals collected at 2200 h but not 0800 h (dissociation constant
      = 14.22 +/- 1.23 pm; maximal binding capacity = 0.88 +/- 0.02 fmol/mg protein);
      and 5) in vitro clock time-dependent inhibition of ACTH-stimulated corticosterone
      production by 1-100 nm melatonin, which was reversed by 1 microm luzindole (a
      melatonin membrane receptor antagonist). Our findings indicate not only
      expression but also high amplitude diurnal variation of functional MT1 melatonin
      receptors in the rat adrenal gland. It is conceivable that plasma melatonin may
      play a role to fine-tune corticosterone production in nocturnal rodents, probably
      contributing to the down slope of the corticosterone rhythm.

PMID- 18039782
TI  - Ghrelin treatment of chronic kidney disease: improvements in lean body mass and
      cytokine profile.
AB  - Chronic kidney disease (CKD) is associated with an increase in inflammatory
      cytokines and can result in cachexia with loss of muscle and fat stores. We
      previously demonstrated the efficacy of treating a model of cancer cachexia with
      ghrelin and a ghrelin receptor agonist. Currently, we examine a surgical model of
      CKD in rats, resulting in uremia and decreased accrual of lean body mass.
      Treatment with ghrelin and two ghrelin receptor agonists (BIM-28125 and BIM
      28131) resulted in increased food intake and an improvement in lean body mass
      accrual that was related in part to a decrease in muscle protein degradation as
      assessed by muscle levels of the 14-kDa actin fragment resulting from cleaved
      actomyosin. Additionally, there was a decrease in circulating inflammatory
      cytokines in nephrectomized animals treated with ghrelin relative to saline
      treatment. Ghrelin-treated animals also had a decrease in the expression of IL-1
      receptor in the brainstem and a decrease in expression of prohormone convertase
      2, an enzyme involved in the processing of proopiomelanocortin to the
      anorexigenic peptide alpha-MSH. We conclude that ghrelin treatment in uremia
      results in improved lean mass accrual in part due to suppressed muscle
      proteolysis and possibly related to antiinflammatory effects.

PMID- 18039784
TI  - Mitogen-stimulated and rapamycin-sensitive glucose transporter 12 targeting and
      functional glucose transport in renal epithelial cells.
AB  - We hypothesized that glucose transporter 12 (GLUT12) is involved in regulation of
      glucose flux in distal renal tubules in response to elevated glucose. We used the
      Madin-Darby canine kidney polarized epithelial cell model and neutralizing
      antibodies to analyze GLUT12 targeting and directional GLUT12-mediated glucose
      transport. At physiological glucose concentrations, GLUT12 was localized to a
      perinuclear position. High glucose and serum treatment resulted in GLUT12
      localization to the apical membrane. This mitogen-stimulated targeting of GLUT12
      was inhibited by rapamycin, the specific inhibitor of mammalian target of
      rapamycin (mTOR). The functional role of GLUT12 was also examined. We constructed
      a GLUT12 cDNA containing a c-Myc epitope tag in the fifth exofacial loop. Assays
      of glucose transport at the apical membrane were performed using Transwell
      filters. By comparing transport assays in the presence of neutralizing anti-c-Myc
      monoclonal antibody, we specifically measured GLUT12-mediated glucose transport
      at the apical surface. GLUT12-mediated glucose transport was mitogen dependent
      and rapamycin sensitive. Our results implicate mTOR signaling in a novel pathway
      of glucose transporter protein targeting and glucose transport. Activity of the
      mTOR pathway has been associated with diabetic kidney disease. Our results
      provide evidence for a link between GLUT12 protein trafficking, glucose transport
      and signaling molecules central to the control of metabolic disease processes.

PMID- 18039785
TI  - A functional nuclear localization signal in insulin-like growth factor binding
      protein-6 mediates its nuclear import.
AB  - IGF binding protein (IGFBP)-6 is a member of the IGFBP family that regulates the
      actions of IGFs. Although IGFBPs exert their functions extracellularly in an
      autocrine/paracrine manner, several members of the family, such as IGFBP-3 and 
      5, possess nuclear localization signals (NLS). To date, no NLS has been described
      for IGFBP-6, an IGFBP that binds preferentially to IGF-II. We report here that
      both exogenous and endogenous IGFBP-6 could be imported into the nuclei of
      rhabdomyosarcoma and HEK-293 cells. Nuclear import of IGFBP-6 was mediated by a
      NLS sequence that bears limited homology to those found in IGFBP-3 and -5. IGFBP
      6 nuclear translocation was an active process that required importins. A peptide
      corresponding to the IGFBP-6 NLS bound preferentially to importin-alpha. A
      comprehensive peptide array study revealed that, in addition to positively
      charged residues such as Arg and Lys, amino acids, notably Gly and Pro, within
      the NLS, played an important part in binding to importins. Overexpression of wild
      type IGFBP-6 increased apoptosis, and the addition of IGF-II did not negate this
      effect. Only the deletion of the NLS segment abolished the apoptosis effect.
      Taken together, these results suggest that IGFBP-6 is translocated to the nucleus
      with functional consequences and that different members of the IGFBP family have
      specific nuclear import mechanisms.

PMID- 18039786
TI  - Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional
      serotonin 2C receptors.
AB  - To investigate how serotonin and leptin interact in the regulation of energy
      balance and glucose homeostasis, we generated a genetic mouse model, the OB2C
      mouse, which lacks functional serotonin 2C receptors and the adipocyte hormone
      leptin. The OB2C mice exhibited a dramatic diabetes phenotype, evidenced by a
      synergistic increase in serum glucose levels and water intake. The severity of
      the animals' diabetes phenotype would not have been predicted from the phenotypic
      characterization of mice bearing mutations of either the leptin (OB mutant mice)
      or the serotonin 2C receptor gene (2C mutant mice). The synergistic impairment in
      glucose homeostasis developed at an age when OB2C mice did not differ in body
      weight from OB mice, suggesting that this impairment was not an indirect
      consequence of increased adiposity. We also demonstrated that the improvement in
      glucose tolerance in wild-type mice treated with the serotonin releaser and
      reuptake inhibitor fenfluramine was blunted in 2C mutant mice. These
      pharmacological and genetic findings provide evidence that the serotonin 2C
      receptor has direct effects on glucose homeostasis.

PMID- 18039787
TI  - Developmental changes of leptin receptors in cerebral microvessels: unexpected
      relation to leptin transport.
AB  - The adipokine leptin participates not only in the regulation of feeding and
      obesity in adults but also in neonatal development. It crosses the blood-brain
      barrier (BBB) by receptor-mediated transport. Leptin concentrations in blood
      differ between neonates and adults. We determined the developmental changes of
      leptin receptor subtypes in the cerebral microvessels composing the BBB and
      examined their expected correlation with leptin transport across the BBB. Total
      RNA was extracted from enriched cerebral microvessels of mice 1, 7, 14, and 60 d
      of age for real-time RT-PCR analysis of leptin receptor subtypes. In cerebral
      microvessels from neonates, ObRa, ObRb, ObRc, and ObRe mRNA were all higher than
      in adults, but ObRd was not detectable. Hypothalamus showed similar age-related
      changes except for ObRb, which was higher in adults. The homologous receptor
      gp130 did not show significant age-related changes in either region. Despite the
      increase of leptin receptors, leptin permeation across the BBB after iv injection
      was less in the neonates. In situ brain perfusion with blood-free buffer showed
      no significant difference in the brain uptake of leptin between neonates and
      adults, indicating an antagonistic role of leptin-binding proteins in the
      circulation, especially the soluble receptor ObRe. The results are consistent
      with our previous finding that ObRe antagonizes leptin endocytosis in cultured
      endothelia and transport from blood to brain in mice. Overall, the developmental
      changes observed for leptin receptors unexpectedly failed to correlate with the
      entry of leptin into brain, and this may indicate different functions of the
      receptors in neonates and adults.

PMID- 18039788
TI  - The anteroventral bed nucleus of the stria terminalis differentially regulates
      hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress.
AB  - The anteroventral region of the bed nucleus of the stria terminalis (BST)
      stimulates hypothalamic-pituitary-adrenocortical (HPA) axis responses to acute
      stress. However, the role of the anterior BST nuclei in chronic drive of the HPA
      axis has yet to be established. Therefore, this study tests the role of the
      anteroventral BST in physiological responses to chronic drive, using a chronic
      variable stress (CVS) model. Male Sprague-Dawley rats received either bilateral
      ibotenate lesions, targeting the anteroventral BST, or vehicle injection into the
      same region. Half of the lesion and control rats were exposed to a 14-d CVS
      paradigm consisting of twice-daily exposure to unpredictable, alternating
      stressors. The remaining rats were nonhandled control animals that remained in
      home cages. On the morning after the end of CVS exposure, all rats were exposed
      to a novel restraint stress challenge. CVS induced attenuated body weight gain,
      adrenal hypertrophy, thymic involution, and enhanced CRH mRNA in
      hypophysiotrophic neurons of the hypothalamic paraventricular nucleus, none of
      which were affected by anteroventral BST lesions. In the absence of CVS, lesions
      attenuated the plasma corticosterone and paraventricular nucleus c-fos mRNA
      responses to the acute restraint stress. In contrast, lesions of the
      anteroventral BST elevated plasma ACTH and corticosterone responses to novel
      restraint in the rats previously exposed to CVS. These data suggest that the
      anterior BST plays very different roles in integrating acute stimulation and
      chronic drive of the HPA axis, perhaps mediated by chronic stress-induced
      recruitment of distinct BST cell groups or functional reorganization of stress
      integrative circuits.

PMID- 18039789
TI  - Opposite regulation of transforming growth factors-beta2 and -beta3 expression in
      the human endometrium.
AB  - TGF-betas have been reported to mediate the repression by progesterone of several
      matrix metalloproteinases in the human endometrium, thereby preventing menstrual
      breakdown. Because of conflicting reports on the expression profiles, source, and
      regulation of the TGF-beta system in this tissue, we investigated by real-time RT
      PCR and ELISA the expression of the three TGF-betas (total and mature forms) and
      their two receptors throughout the menstrual cycle, and their regulation by
      ovarian steroids in cultured explants including their microdissected epithelial
      and stromal compartments. Regulation by cAMP and MAPK was further investigated.
      This comprehensive study on a large collection of endometrial samples evidenced a
      differential regulation of TGF-beta isoforms expression, both in vivo and in
      explant culture. In vivo, TGF-beta2 increased by about 5-fold at the mid-late
      secretory phase then declined after menstruation; TGF-beta3 increased at
      menstruation and remained high during the proliferative phase; TGF-beta1 was
      maximal at menstruation. In explants cultured without ovarian steroids both TGF
      beta2 and -beta3 were preferentially expressed in the stroma. Ovarian steroids
      strongly repressed both TGF-beta2 and -beta3 in stroma but only TGF-beta2 in
      glands. cAMP prevented inhibition by ovarian steroids of TGF-beta2 but not 
      beta3. In presence of ovarian steroids, MAPK inhibitors (p38 and ERK pathways)
      stimulated TGF-beta3 but inhibited TGF-beta2 expression. In conclusion, TGF-beta2
      and -beta3 are differentially expressed during the menstrual cycle and regulated
      by progesterone in epithelial vs stromal cells. The opposite regulation of TGF
      beta2 and -beta3 by cAMP and MAPK could account for their distinct expression in
      vivo.

PMID- 18039790
TI  - Impact of transgenic overexpression of SH2-containing inositol 5'-phosphatase 2
      on glucose metabolism and insulin signaling in mice.
AB  - SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a 5'-lipid phosphatase
      hydrolyzing the phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P(3) to
      PI(3,4)P(2) in the regulation of insulin signaling, and is shown to be increased
      in peripheral tissues of diabetic C57BL/KSJ-db/db mice. To clarify the impact of
      SHIP2 in the pathogenesis of insulin resistance with type 2 diabetes, we
      generated transgenic mice overexpressing SHIP2. The body weight of transgenic
      mice increased by 5.0% (P < 0.05) compared with control wild-type littermates on
      a normal chow diet, but not on a high-fat diet. Glucose tolerance and insulin
      sensitivity were mildly but significantly impaired in the transgenic mice only
      when maintained on the normal chow diet, as shown by 1.2-fold increase in glucose
      area under the curve over control levels at 9 months old. Insulin-induced
      phosphorylation of Akt was decreased in the SHIP2-overexpressing fat, skeletal
      muscle, and liver. In addition, the expression of hepatic mRNAs for glucose-6
      phosphatase and phosphoenolpyruvate carboxykinase was increased, that for sterol
      regulatory element-binding protein 1 was unchanged, and that for glucokinase was
      decreased. Consistently, hepatic glycogen content was reduced in the 9-month-old
      transgenic mice. Structure and insulin content were histologically normal in the
      pancreatic islets of transgenic mice. These results indicate that increased
      abundance of SHIP2 in vivo contributes, at least in part, to the impairment of
      glucose metabolism and insulin sensitivity on a normal chow diet, possibly by
      attenuating peripheral insulin signaling and by altering hepatic gene expression
      for glucose homeostasis.

PMID- 18039791
TI  - Caveolin-1 down-regulation inhibits insulin-like growth factor-I receptor signal
      transduction in H9C2 rat cardiomyoblasts.
AB  - Caveolin (Cav)-1, the major caveolar protein, directly interacts with IGF-I
      receptor (IGF-IR) and its intracellular substrates. To determine the role of Cav
      1 in IGF-IR signaling, we transfected H9C2 cells with small interfering RNA
      specific for Cav-1-siRNA. The selective down-regulation of Cav-1 (90%) was
      associated with a smaller reduction of Cav-2, whereas Cav-3 expression was
      unaffected. A significant reduction of IGF-IR tyrosine phosphorylation in Cav-1
      siRNA H9C2 cells was found compared with H9C2 control cells (Ctr-siRNA). The
      reduced IGF-IR autophosphorylation resulted in a decrease of insulin receptor
      substrate-1, Shc, and Akt activation. In addition, in Cav-1-siRNA H9C2 cells, IGF
      I did not prevent apoptosis, suggesting that Cav-1 is required to mediate the
      antiapoptotic effect of IGF-I in cardiomyoblasts. The down-regulation of Cav-1
      decreased IGF-IR activation and affected the ability of IGF-I to prevent
      apoptosis after serum withdrawal also in human umbilical vein endothelial cells.
      These results demonstrate that: 1) Cav-1 down-regulation negatively affects IGF
      IR tyrosine phosphorylation; 2) this effect causes a reduced activation of
      insulin receptor substrate-1, Shc, and Akt; and 3) Cav-1 is involved in IGF-IR
      antiapoptotic signaling after serum deprivation.

PMID- 18039792
TI  - Glucocorticoid receptor is required for skin barrier competence.
AB  - To investigate the contribution of the glucocorticoid receptor (GR) in skin
      development and the mechanisms underlying this function, we have analyzed two
      mouse models in which GR has been functionally inactivated: the knockout GR(-/-)
      mice and the dimerization mutant GR(dim/dim) that mediates defective DNA binding
      dependent transcription. Because GR null mice die perinatally, we evaluated skin
      architecture of late embryos by histological, immunohistochemical, and electron
      microscopy studies. Loss of function of GR resulted in incomplete epidermal
      stratification with dramatically abnormal differentiation of GR(-/-), but not
      GR(+/-) embryos, as demonstrated by the lack of loricrin, filaggrin, and
      involucrin markers. Skin sections of GR(-/-) embryos revealed edematous basal and
      lower spinous cells, and electron micrographs showed increased intercellular
      spaces between keratinocytes and reduced number of desmosomes. The absent
      terminal differentiation in GR(-/-) embryos correlated with an impaired
      activation of caspase-14, which is required for the processing of profilaggrin
      into filaggrin at late embryo stages. Accordingly, the skin barrier competence
      was severely compromised in GR(-/-) embryos. Cultured mouse primary keratinocytes
      from GR(-/-) mice formed colonies with cells of heterogeneous size and morphology
      that showed increased growth and apoptosis, indicating that GR regulates these
      processes in a cell-autonomous manner. The activity of ERK1/2 was constitutively
      augmented in GR(-/-) skin and mouse primary keratinocytes relative to wild type,
      which suggests that GR modulates skin homeostasis, at least partially, by
      antagonizing ERK function. Moreover, the epidermis of GR(+/dim) and GR(dim/dim)
      embryos appeared normal, thus suggesting that DNA-binding-independent actions of
      GR are sufficient to mediate epidermal and hair follicle development during
      embryogenesis.

PMID- 18039793
TI  - Hexose-6-phosphate dehydrogenase and 11beta-hydroxysteroid dehydrogenase-1 tissue
      distribution in the rat.
AB  - Intracellular concentrations of the glucocorticoids cortisol and corticosterone
      are modulated by the enzymes 11beta-hydroxysteroid dehydrogenase (11beta-HSD) 1
      and 2. 11beta-HSD1 is a reduced nicotinamide adenine dinucleotide phosphate
      (NADPH)-dependent microsomal reductase that converts the inactive glucocorticoids
      cortisone and 11-dehydrocorticosterone to their active forms, cortisol and
      corticosterone. Hexose-6-phosphate dehydrogenase (H6PDH) is an enzyme that
      generates NADPH from oxidized NADP (NADP(+)) within the endoplasmic reticulum. In
      the absence of NADPH or H6PDH to regenerate NADPH, 11beta-HSD1 acts as a
      dehydrogenase and inactivates glucocorticoids, as does 11beta-HSD2. A monoclonal
      antibody against H6PDH was produced to study the possibility that 11beta-HSD1 in
      the absence of H6PDH may be responsible for hydroxysteroid dehydrogenase activity
      in tissues that do not express significant amounts of 11beta-HSD2. H6PDH and
      11beta-HSD1 expression was surveyed in a variety of rat tissues by real-time RT
      PCR, Western blot analysis, and immunohistochemistry. H6PDH was found in a wide
      variety of tissues, with the greatest concentrations in the liver, kidney, and
      Leydig cells. Although the brain as a whole did not express significant amounts
      of H6PDH, some neurons were clearly immunoreactive by immunohistochemistry. H6PDH
      was amply expressed in most tissues examined in which 11beta-HSD1 was also
      expressed, with the notable exception of the renal interstitial cells, in which
      dehydrogenase activity by 11beta-HSD1 probably moderates activation of the
      glucocorticoid receptor because rat renal interstitial cells do not have
      significant amounts of mineralocorticoid receptors. This antibody against the
      H6PDH should prove useful for further studies of enzyme activity requiring NADPH
      generation within the endoplasmic reticulum.

PMID- 18039794
TI  - Evaluation of conventional microbiological procedures and molecular genetic
      techniques for diagnosis of infections in patients with implanted orthopedic
      devices.

PMID- 18039795
TI  - In vitro bactericidal activity of Streptococcus pneumoniae and bactericidal
      susceptibility of Staphylococcus aureus strains isolated from cocolonized versus
      noncocolonized children.
AB  - Streptococcus pneumoniae is bactericidal to Staphylococcus aureus in vitro. To
      determine whether this in vitro effect accounts for the inverse relation between
      S. pneumoniae and S. aureus colonization reported in previous epidemiologic
      studies, we compared S. pneumoniae and S. aureus strains from cocolonized
      children to those from noncocolonized children. Cocolonizing pneumococci were
      less bactericidal and cocolonizing staphylococci less susceptible to this effect;
      however, the magnitude of the effect was small. Thus, in vitro killing is not the
      major determinant of the pattern of cocolonization.

PMID- 18039797
TI  - Loop-mediated isothermal amplification method targeting the TTS1 gene cluster for
      detection of Burkholderia pseudomallei and diagnosis of melioidosis.
AB  - Melioidosis is a severe infection caused by Burkholderia pseudomallei. The timely
      implementation of effective antimicrobial treatment requires rapid diagnosis.
      Loop-mediated isothermal amplification (LAMP) targeting the TTS1 gene cluster was
      developed for the detection of B. pseudomallei. LAMP was sensitive and specific
      for the laboratory detection of this organism. The lower limit of detection was
      38 genomic copies per reaction, and LAMP was positive for 10 clinical B.
      pseudomallei isolates but negative for 5 B. thailandensis and 5 B. mallei
      isolates. A clinical evaluation was conducted in northeast Thailand to compare
      LAMP to an established real-time PCR assay targeting the same TTS1 gene cluster.
      A total of 846 samples were obtained from 383 patients with suspected
      melioidosis, 77 of whom were subsequently diagnosed with culture-confirmed
      melioidosis. Of these 77 patients, a positive result was obtained from one or
      more specimens by PCR in 26 cases (sensitivity, 34%; 95% confidence interval
      [CI], 23.4 to 45.4%) and by LAMP in 34 cases (sensitivity, 44%; 95% CI, 32.8 to
      55.9%) (P = 0.02). All samples from 306 patients that were culture negative for
      B. pseudomallei were negative by PCR (specificity, 100%; 95% CI, 98.8 to 100%),
      but 5 of 306 patients (1.6%) were positive by LAMP (specificity, 98.4%; 95% CI,
      96.2 to 99.5%) (P = 0.03). The diagnostic accuracies of PCR and LAMP were 86.7%
      (95% CI, 82.9 to 89.9%) and 87.5% (95% CI, 83.7 to 90.6%), respectively (P =
      0.47). Both assays were very insensitive when applied to blood samples; PCR and
      LAMP were positive for 0 and 1 of 44 positive blood cultures, respectively. The
      PCR and LAMP assays evaluated here are not sufficiently sensitive to replace
      culture in our clinical setting.

PMID- 18039796
TI  - Comparison of seven techniques for typing international epidemic strains of
      Clostridium difficile: restriction endonuclease analysis, pulsed-field gel
      electrophoresis, PCR-ribotyping, multilocus sequence typing, multilocus variable
      number tandem-repeat analysis, amplified fragment length polymorphism, and
      surface layer protein A gene sequence typing.
AB  - Using 42 isolates contributed by laboratories in Canada, The Netherlands, the
      United Kingdom, and the United States, we compared the results of analyses done
      with seven Clostridium difficile typing techniques: multilocus variable-number
      tandem-repeat analysis (MLVA), amplified fragment length polymorphism (AFLP),
      surface layer protein A gene sequence typing (slpAST), PCR-ribotyping,
      restriction endonuclease analysis (REA), multilocus sequence typing (MLST), and
      pulsed-field gel electrophoresis (PFGE). We assessed the discriminating ability
      and typeability of each technique as well as the agreement among techniques in
      grouping isolates by allele profile A (AP-A) through AP-F, which are defined by
      toxinotype, the presence of the binary toxin gene, and deletion in the tcdC gene.
      We found that all isolates were typeable by all techniques and that
      discrimination index scores for the techniques tested ranged from 0.964 to 0.631
      in the following order: MLVA, REA, PFGE, slpAST, PCR-ribotyping, MLST, and AFLP.
      All the techniques were able to distinguish the current epidemic strain of C.
      difficile (BI/027/NAP1) from other strains. All of the techniques showed multiple
      types for AP-A (toxinotype 0, binary toxin negative, and no tcdC gene deletion).
      REA, slpAST, MLST, and PCR-ribotyping all included AP-B (toxinotype III, binary
      toxin positive, and an 18-bp deletion in tcdC) in a single group that excluded
      other APs. PFGE, AFLP, and MLVA grouped two, one, and two different non-AP-B
      isolates, respectively, with their AP-B isolates. All techniques appear to be
      capable of detecting outbreak strains, but only REA and MLVA showed sufficient
      discrimination to distinguish strains from different outbreaks.

PMID- 18039798
TI  - Application of a microsphere-based array for rapid identification of
      Acinetobacter spp. with distinct antimicrobial susceptibilities.
AB  - Acinetobacter spp. have emerged as important nosocomial and multidrug-resistant
      pathogens in the last decade. A. calcoaceticus, A. baumannii, Acinetobacter
      genospecies 3, and Acinetobacter genospecies 13TU are genetically closely related
      and are referred to as the A. calcoaceticus-A. baumannii complex (ACB complex).
      Distinct Acinetobacter spp. may be associated with differences in antimicrobial
      susceptibility, so it is important to identify Acinetobacter spp. at the species
      level. We developed a microsphere-based array that combines an allele-specific
      primer extension assay and microsphere hybridization for the identification of
      Acinetobacter spp. This assay can discriminate the 13 different Acinetobacter
      spp. in less than 8.5 h, and it has high specificity without causing cross
      reactivity with 14 other common nosocomial bacterial species. The sensitivity of
      this assay was 100 A. baumannii cells per ml of blood, and it could discriminate
      multiple species in various mixture ratios. The developed assay could
      differentiate clinical Acinetobacter spp. isolates with a 90% identification
      rate. The antimicrobial susceptibility test showed that A. baumannii isolates
      were resistant to most antimicrobial agents other than imipenem, while the
      genospecies 3 and 13TU isolates were more susceptible to most antimicrobial
      agents, especially ciprofloxacin and ampicillin-sulbactam. These results
      supported the idea that this assay possibly could be applied to clinical samples
      and provide accurate species identification, which might be helpful for
      clinicians when they are treating infections caused by Acinetobacter spp.

PMID- 18039800
TI  - Methicillin-resistant Staphylococcus aureus nasal carriage among injection drug
      users: six years later.
AB  - A survey in 2000 to detect methicillin-resistant Staphylococcus aureus (MRSA)
      colonization in Vancouver downtown east side injection drug users (IDUs) revealed
      an MRSA nasal colonization incidence of 7.4%. This is a follow-up study to
      determine the current prevalence of MRSA colonization and to further characterize
      the isolates and risk factors for colonization. In this point prevalence study of
      MRSA nasal carriage among IDUs, nasal swabs were cultured to detect S. aureus.
      Isolates were studied for their antimicrobial susceptibility patterns and the
      presence of mecA and Panton-Valentine leukocidin (PVL) genes and by pulsed-field
      gel electrophoresis (PFGE). S. aureus was isolated from 119 of 301 (39.5%)
      samples; three (2.5%) participants had both methicillin-sensitive S. aureus
      (MSSA) and MRSA, resulting in 122 isolates. Of these, 54.1% were MSSA and 45.9%
      were MRSA, with an overall MRSA rate of 18.6%. USA-300 (CMRSA-10) accounted for
      75% of all MRSA isolates; 25% were USA-500 (CMRSA-5). None of the USA-500
      isolates were positive for PVL; 41 (97.6%) USA-300 isolates contained PVL. One
      MSSA isolate, from an individual also carrying USA-300, was positive for PVL. The
      PFGE pattern of this MSSA isolate was related to that of the MRSA strain. The
      antibiograms of USA-300 compared to USA-500 isolates showed 100% versus 7.1%
      susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX) and 54.8% versus 7.1%
      susceptibility to clindamycin. MRSA nasal colonization in this population has
      increased significantly within the last 6 years, with USA-300 replacing the
      previous strain. Most of these strains are PVL positive, and all are susceptible
      to TMP-SMX.

PMID- 18039802
TI  - Factors affecting use of insulin pens by patients with type 2 diabetes.
AB  - OBJECTIVE: To assess factors that might affect patient use of insulin pens.
      RESEARCH DESIGN AND METHODS: Patients (n = 600: 300 using vial and syringe and
      300 using pen) were recruited from national panels to participate in computer
      assisted telephone interviews. Measures included: demographic characteristics;
      diabetes treatment and self-care factors; perceptions of pen convenience,
      clinical efficacy, facilitation of self-care, and cost; and degree of physicians'
      recommending pen use. RESULTS: Physician recommendation of pen use powerfully
      discriminated pen users from nonusers (odds ratio 135.6). Other factors that
      discriminated pen users included physicians' presenting pens as an option (14.1)
      and patient perceptions that pens facilitate diabetes self-care (20.2) and are
      not costly (4.8). CONCLUSIONS: The physician's role in presenting the pen as an
      option and recommending pen use was a critical factor in patient pen use.
      Enhanced physician education regarding the potential benefits of pen use and
      encouraging physicians to discuss pen use with patients could improve diabetes
      outcomes.

PMID- 18039801
TI  - Colonization and persistence of antibiotic-resistant Enterobacteriaceae strains
      in infants nursed in two neonatal intensive care units in East London, United
      Kingdom.
AB  - Stool samples were collected from infants nursed in two neonatal intensive care
      units (NICUs) in East London, United Kingdom. The aim of the study was to
      determine the incidence of and risk factors for the carriage of multiresistant
      Enterobacteriaceae strains (MRE; resistant to three or more classes of
      antibiotic) and the extent of the persistence of resistant strains following
      discharge. Sixty-two (50%) of 124 infants had acquired MRE by 2 weeks of
      postnatal age, and 69 (56%) infants had acquired MRE by discharge. The
      proportions of infants at 2 weeks carrying strains that were resistant to
      antibiotics were the following: tetracycline, 79%; amoxicillin, 78%;
      cephalosporins, 31%; trimethoprim, 20%; piperacillin-tazobactam, 11%;
      chloramphenicol, 9%; and aminoglycoside, 4%. A gestational age of less than 26
      weeks was a risk factor for colonization with MRE at discharge, but not at 2
      weeks. Analysis within a NICU showed that exposure of an infant to a specific
      antibiotic in the NICU was not a risk factor for the carriage of a strain
      resistant to that antibiotic. Estimates of persistence from discharge to 6 months
      were the following: for tetracycline, 57% (95% confidence intervals [CI], 0.35 to
      0.87); chloramphenicol, 49% (95% CI, 0.20 to 0.83); trimethoprim, 45% (95% CI,
      0.22 to 0.74); piperacillin-tazobactam, 42% (95% CI, 0.20 to 0.71); and
      augmentin, 34% (95% CI, 0.11 to 0.66). Strains resistant to cephalosporins or
      aminoglycosides showed lower levels of persistence. Nine of 34 infants (26.5%)
      with Escherichia coli and 4 (7.1%) of 56 infants with Klebsiella spp. at
      discharge carried strains indistinguishable by randomly amplified polymorphic DNA
      and antibiotic susceptibility patterns at 6 months. MRE were found at high
      frequency in the infants during their stay in the NICU and persisted in a
      proportion of infants.

PMID- 18039803
TI  - Association between serum bioavailable testosterone concentration and the ratio
      of glycated albumin to glycated hemoglobin in men with type 2 diabetes.
AB  - OBJECTIVE: Testosterone stimulates erythropoiesis and thus glycated hemoglobin
      (A1C) values may be relatively low in male diabetic patients with hypogonadism.
      We therefore investigated relationships between serum bioavailable testosterone
      concentration and the ratio of glycated albumin (GA) to A1C and between serum
      bioavailable testosterone and hemoglobin concentrations in men with type 2
      diabetes. RESEARCH DESIGN AND METHODS: The above relationships were investigated
      in 222 consecutive men with type 2 diabetes. We also investigated how the ratio
      of GA to A1C is related to other variables such as age, BMI, and degree of
      diabetic microangiopathy. RESULTS: Mean ratio of GA to A1C was 2.94 +/- 0.38.
      Serum bioavailable testosterone concentration correlated positively with
      hemoglobin concentration (r = 0.368, P < 0.0001) and negatively with the ratio of
      GA to A1C (r = -0.278, P < 0.0001). Multiple regression analyses identified serum
      bioavailable testosterone concentration (beta = 0.187, P = 0.0062), age (beta = 
      0.204, P = 0.0075), BMI (beta = 0.151, P = 0.0302), systolic blood pressure (beta
      = 0.173, P = 0.0090), and plasma total cholesterol (beta = 0.155, P = 0.0141) as
      independent determinants of hemoglobin concentration; moreover, serum
      bioavailable testosterone concentration (beta = -0.155, P = 0.0381) and plasma
      total cholesterol (beta = -0.170, P = 0.0144) were identified as independent
      determinants of the ratio of GA to A1C. CONCLUSIONS: Serum bioavailable
      testosterone concentration correlated positively with hemoglobin concentration
      and negatively with the ratio of GA to A1C in men with type 2 diabetes, which may
      lead to underestimation of A1C in hypogonadal men with type 2 diabetes.

PMID- 18039804
TI  - Prevalence of polyneuropathy in pre-diabetes and diabetes is associated with
      abdominal obesity and macroangiopathy: the MONICA/KORA Augsburg Surveys S2 and
      S3.
AB  - OBJECTIVE: It is controversial whether there is a glycemic threshold above which
      polyneuropathy develops and which are the most important factors associated with
      polyneuropathy in the general population. The aim of this study was to determine
      the prevalence and risk factors of polyneuropathy in subjects with diabetes,
      impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or normal
      glucose tolerance (NGT). RESEARCH DESIGN AND METHODS: Subjects with diabetes (n =
      195) and control subjects matched for age and sex (n = 198) from the population
      based MONICA (Monitoring Trends and Determinants on Cardiovascular Diseases)/KORA
      (Cooperative Research in the Region of Augsburg) Augsburg Surveys 1989/1990 (S2)
      and 1994/1995 (S3) aged 25-74 years were contacted again and assessed in
      1997/1998 by the Michigan Neuropathy Screening Instrument using a score cut point
      >2. An oral glucose tolerance test was performed in the control subjects.
      RESULTS: Among the control subjects, 46 (23.2%) had IGT, 71 (35.9%) had IFG, and
      81 had NGT. The prevalence of polyneuropathy was 28.0% in the diabetic subjects,
      13.0% in those with IGT, 11.3% in those with IFG, and 7.4% in those with NGT (P
      <or= 0.05 for diabetes vs. NGT, IFG, and IGT). In the entire population studied
      (n = 393), age, waist circumference, and diabetes were independent factors
      significantly associated with polyneuropathy, whereas in the diabetic group
      polyneuropathy was associated with age, waist circumference, and peripheral
      arterial disease (PAD) (all P < 0.05). CONCLUSIONS: The prevalence of
      polyneuropathy is slightly increased in individuals with IGT and IFG compared
      with those with NGT. The association with waist circumference and PAD suggests
      that the latter and abdominal obesity may constitute important targets for
      strategies to prevent diabetic polyneuropathy.

PMID- 18039799
TI  - Relationships of nontypeable Haemophilus influenzae strains to hemolytic and
      nonhemolytic Haemophilus haemolyticus strains.
AB  - Haemophilus influenzae is both a human respiratory pathogen and pharyngeal
      commensal, while H. haemolyticus, the closest phylogenetic relative of H.
      influenzae, is arguably a strict pharyngeal commensal. A hemolytic phenotype has
      historically differentiated H. haemolyticus from H. influenzae, but the recent
      recognition of significant nonhemolytic H. haemolyticus colonization has
      decreased this trait's resolvability. Given this and the potential of
      recombination between the species, we examined the distribution of microbiologic
      and molecular traits between collections of H. influenzae and H. haemolyticus
      strains separated within a dendrogram obtained by multilocus sequence analysis
      (MLSA). All strains hybridizing with a probe to iga, a gene encoding an
      immunoglobulin A protease of H. influenzae, clustered apart from strains that did
      not hybridize with the probe. Other traits also segregated significantly along
      this division, suggesting a separation of the species. Of note, the LOS genes
      licA, lic2A, and lgtC of H. influenzae were approximately 2, 6, and 54 times,
      respectively, more prevalent in H. influenzae than in H. haemolyticus. In
      contrast to species separation, interspecies recombination was evidenced by the
      inability of single gene sequences to phylogenetically separate the species and
      by the "fuzzy" distribution of some species-specific traits across the species
      dividing line. Together, these data support the historically accurate and
      pragmatic division of these species while recognizing their potential for
      recombination. Future comparative genomic studies identifying common and
      distinctive genes could be useful in evaluating their role in the commensal or
      virulent growth, respectively, of H. influenzae.

PMID- 18039805
TI  - Skin autofluorescence: a tool to identify type 2 diabetic patients at risk for
      developing microvascular complications.
AB  - OBJECTIVE: Skin autofluorescence is a noninvasive measure of the level of tissue
      accumulation of advanced glycation end products, representing cumulative glycemic
      and oxidative stress. Recent studies have already shown a relationship between
      skin autofluorescence and diabetes complications, as well as the predictive value
      of skin autofluorescence for total and cardiovascular mortality in type 2
      diabetes. Our aim was to investigate the predictive value of skin
      autofluorescence for the development of microvascular complications in type 2
      diabetes. RESEARCH DESIGN AND METHODS: At baseline, skin autofluorescence of 973
      type 2 diabetic patients with well-controlled diabetes was noninvasively measured
      with an autofluorescence reader. The aggregate clinical outcome was defined as
      the development of any diabetes-associated microvascular complication of 881
      surviving patients, which was assessed at baseline and at the end of follow-up.
      Single end points were the development of diabetes-associated retinopathy,
      neuropathy, and (micro)albuminuria. RESULTS: After a mean follow-up period of 3.1
      years, baseline skin autofluorescence was significantly higher in patients who
      developed any microvascular complication, neuropathy, or (micro)albuminuria but
      not in those who developed retinopathy. Multivariate analyses showed skin
      autofluorescence as a predictor for development of any microvascular complication
      along with A1C, for development of neuropathy along with smoking, and for
      development of (micro)albuminuria together with sex, A1C, and diabetes duration.
      Skin autofluorescence did not have predictive value for the development of
      retinopathy, albeit diabetes duration did. CONCLUSIONS: Our study is the first
      observation of skin autofluorescence measurement as an independent predictor of
      development of microvascular complications in type 2 diabetes.

PMID- 18039806
TI  - P-glycoprotein restricts the penetration of oseltamivir across the blood-brain
      barrier.
AB  - Oseltamivir is an ethyl ester prodrug of [3R,4R,5S]-4-acetamido-5-amino-3-(1
      ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), the anti
      influenza drug. Abnormal behavior has been suspected to be associated with
      oseltamivir medication in Japan. The purpose of the present study is to examine
      the involvement of transporters in the brain distribution of oseltamivir and its
      active form Ro 64-0802 across the blood-brain barrier (BBB). The brain-to-plasma
      concentration ratio (K(p,brain)) of oseltamivir after i.v. infusion of
      oseltamivir in FVB mice was increased by pretreatment with N-(4-[2-(1,2,3,4
      tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9
      oxo-4-acridine carboxamide (GF120918), a dual inhibitor for P-glycoprotein (P-gp)
      and breast cancer resistance protein (Bcrp), whereas that of Ro 64-0802 was only
      slightly increased. Furthermore, the distribution volume of Ro 64-0802 following
      i.v. administration of Ro 64-0802 in the brain was similar to the capillary
      volume, suggesting its minimal distribution. The K(p,brain) value of oseltamivir
      in multidrug-resistant (Mdr) 1a/1b P-gp knockout mice was 5.5-fold higher than
      that in wild-type mice and comparable with that obtained by pretreatment with
      GF120918, whereas it was unchanged in Bcrp knockout mice. The K(p,brain) value of
      oseltamivir was significantly higher in newborn rats, which is in good agreement
      with the ontogenetic expression profile of P-gp. Intracellular accumulation of
      oseltamivir was lower in human and mouse P-gp-expressing cells, which was
      reversed by P-gp inhibitor valspodar (PSC833). These results suggest that P-gp
      limits the brain uptake of oseltamivir at the BBB and that Ro 64-0802 itself
      barely crosses the BBB. However, it may be possible that Ro 64-0802 is formed in
      the brain from the oseltamivir, considering the presence of carboxylesterase in
      the brain endothelial cells.

PMID- 18039807
TI  - Taxane's substituents at C3' affect its regioselective metabolism: different in
      vitro metabolism of cephalomannine and paclitaxel.
AB  - To investigate how taxane's substituents at C3' affect its metabolism, we
      compared the metabolism of cephalomannine and paclitaxel, a pair of analogs that
      differ slightly at the C3' position. After cephalomannine was incubated with
      human liver microsomes in an NADPH-generating system, two monohydroxylated
      metabolites (M1 and M2) were detected by liquid chromatography/tandem mass
      spectrometry. C4'' (M1) and C6alpha (M2) were proposed as the possible
      hydroxylation sites, and the structure of M1 was confirmed by (1)H NMR. Chemical
      inhibition studies and assays with recombinant human cytochromes P450 (P450s)
      indicated that 4''-hydroxycephalomannine was generated predominantly by CYP3A4
      and 6alpha-hydroxycephalomannine by CYP2C8. The overall biotransformation rate
      between paclitaxel and cephalomannine differed slightly (184 vs. 145
      pmol/min/mg), but the average ratio of metabolites hydroxylated at the C13 side
      chain to C6alpha for paclitaxel and cephalomannine varied significantly (15:85
      vs. 64:36) in five human liver samples. Compared with paclitaxel, the major
      hydroxylation site transferred from C6alpha to C4'', and the main metabolizing
      P450 changed from CYP2C8 to CYP3A4 for cephalomannine. In the incubation system
      with rat or minipig liver microsomes, only 4''-hydroxycephalomannine was
      detected, and its formation was inhibited by CYP3A inhibitors. Molecular docking
      by AutoDock suggested that cephalomannine adopted an orientation in favor of 4''
      hydroxylation, whereas paclitaxel adopted an orientation favoring 3'-p
      hydroxylation. Kinetic studies showed that CYP3A4 catalyzed cephalomannine more
      efficiently than paclitaxel due to an increased V(m). Our results demonstrate
      that relatively minor modification of taxane at C3' has major consequence on the
      metabolism.

PMID- 18039808
TI  - Pharmacokinetics and metabolism of ligustilide, a major bioactive component in
      Rhizoma Chuanxiong, in the rat.
AB  - Ligustilide is the most abundant bioactive ingredient in Rhizoma Chuanxiong, a
      Chinese medicinal herb commonly used for the treatment of cardiovascular
      ailments. The present study reported, for the first time, the pharmacokinetics of
      ligustilide, administered in its pure form and in an herbal extract, in rats.
      After i.v. administration of pure ligustilide, it was distributed extensively
      (V(d), 3.76 +/- 1.23 l/kg) and eliminated rapidly (t(1/2), 0.31 +/- 0.12 h). The
      i.v. clearance (CL) of ligustilide after Chuanxiong extract administration was
      significantly higher than that dosed in its pure form [CL, 20.35 +/- 3.05 versus
      9.14 +/- 1.27 l/h/kg, p < 0.01; area under the curve (AUC), 0.79 +/- 0.10 versus
      1.81 +/- 0.24 mg x h/l, p < 0.01], suggesting significant interaction between
      ligustilide and components present in the extract. Dose-dependent
      pharmacokinetics was observed after i.p. administration, and a significantly
      higher dose-normalized AUC (1.77 +/- 0.23 mg x h/l) at 52 mg/kg was obtained than
      that at 26 mg/kg (0.93 +/- 0.07 mg x h/l, p < 0.05). Oral bioavailability of
      ligustilide was low (2.6%), which was partly because of extensive first-pass
      metabolism in the liver. Seven metabolites of ligustilide were identified, and
      three of them were unequivocally characterized as butylidenephthalide,
      senkyunolide I, and senkyunolide H. These three compounds also occurred naturally
      in the herb and were reported to be bioactive.

PMID- 18039809
TI  - Biotransformation of lithocholic acid by rat hepatic microsomes: metabolite
      analysis by liquid chromatography/mass spectrometry.
AB  - Lithocholic acid is a lipid-soluble hepatotoxic bile acid that accumulates in the
      liver during cholestasis. A potential detoxification pathway for lithocholic acid
      involves hydroxylation by hepatic cytochrome P450 (P450) enzymes. The purpose of
      the present study was to identify the hepatic microsomal metabolites of
      lithocholic acid by liquid chromatography/mass spectrometry and to determine the
      P450 enzymes involved. Incubation of lithocholic acid with rat hepatic microsomes
      and NADPH produced murideoxycholic acid (MDCA), isolithocholic acid (ILCA), and 3
      keto-5beta-cholanic acid (3KCA) as major metabolites and 6-ketolithocholic acid
      and ursodeoxycholic acid as minor metabolites. Experiments with hepatic
      microsomes prepared from rats pretreated with P450 inducers and with inhibitory
      antibodies indicated that CYP2C and CYP3A enzymes contribute to microsomal MDCA
      formation. Results obtained with a panel of recombinant P450 enzymes and CYP2D6
      antiserum showed that CYP2D1 can also catalyze MDCA formation. Similar
      experimental evidence revealed that formation of 3KCA was mediated primarily by
      CYP3A enzymes. ILCA formation appeared to be catalyzed by a distinct pathway
      mediated largely by microsomal non-P450 enzymes. Based on the results obtained
      using lithocholic acid and 3KCA as substrates, a mechanism for the formation of
      ILCA involving a geminal diol intermediate is outlined. In conclusion,
      lithocholic acid was extensively metabolized by multiple P450 enzymes with the
      predominant biotransformation pathway being hydroxylation at the 6beta-position.
      This study provides an insight into possible routes of detoxification of
      lithocholic acid.

PMID- 18039810
TI  - Regulation of the rat UGT1A6 by glucocorticoids involves a cryptic glucocorticoid
      response element.
AB  - Glucocorticoids precociously induce fetal rat UGT1A6 and potentiate polycyclic
      aromatic hydrocarbon (PAH)-dependent induction of this enzyme in vivo and in
      isolated rat hepatocytes. To establish whether induction was due to
      glucocorticoid receptor (GR), luciferase reporter vectors were tested in
      transfection assays with HepG2 cells. Using a reporter construct containing
      approximately 2.26 kilobases of the 5'-flanking region of the UGT1A6-noncoding
      leader exon (A1*), dexamethasone increased basal activity 3- to 7-fold in cells
      cotransfected with an expression plasmid for GR. PAH increased gene expression 23
      fold, but the presence of dexamethasone only induced PAH-dependent expression by
      1.5-fold, suggesting interaction between GR and the aryl hydrocarbon (Ah)
      receptor. Furthermore, the GR antagonist RU 38486 [17beta-hydroxy-11beta-(4
      dimethylamino-phenyl)-17alpha-(prop-1-ynyl)-estra-4,9-dien-3-one] was a partial
      agonist that increased, rather than inhibited, basal activity 3-fold. 5'-deletion
      analysis defined the 5'-boundary for a functional glucocorticoid-responsive unit
      between base pairs -141 and -118 relative to the transcription start site. This
      region contains the Ah receptor response element (AhRE), and both PAH and
      glucocorticoid-dependent gene activation were lost when this area was deleted.
      Mutation of a single base pair located in the AhRE region simultaneously reduced
      induction by PAH and increased glucocorticoid induction. Thus, the sequences of
      both the AhRE and glucocorticoid response elements seem to overlap, suggesting
      that Ah receptor binding may decrease glucocorticoid-dependent induction due to
      interactions of these two cis-acting elements. Mutation of a putative GRE located
      between base pair -81 and -95 reduced, but did not completely eliminate,
      glucocorticoid-dependent induction of the reporter, suggesting that a nonclassic
      mechanism of induction is involved in this response.

PMID- 18039811
TI  - Coma with diffuse white matter hemorrhages in juvenile diabetic ketoacidosis.
AB  - Cerebral edema is the most common neurologic complication of diabetic
      ketoacidosis in children. A minority of young patients with intracerebral crises
      in diabetic ketoacidosis present with cerebrovascular accidents. We report 2
      adolescent patients with diabetic ketoacidosis who presented with coma and
      diffuse white matter hemorrhages in the absence of either cerebral edema or
      cerebrovascular accidents. These 2 cases illustrate a novel clinical and
      neuropathologic description of diffuse white matter hemorrhages, possibly related
      to a cytotoxic process as the underlying mechanism. These case descriptions
      emphasize that pediatric patients with diabetic ketoacidosis and coma can present
      with pathology not related to either cerebral edema or cerebrovascular accidents.

PMID- 18039812
TI  - Nephropathy in type 1 diabetes is diminished in carriers of HLA-DRB1*04: the
      genetics of kidneys in diabetes (GoKinD) study.
AB  - OBJECTIVE: The purpose of this study was to examine whether known genetic risk
      factors for type 1 diabetes (HLA-DRB1, -DQA1, and -DQB1 and insulin locus) play a
      role in the etiology of diabetic nephropathy. RESEARCH DESIGN AND METHODS;
      Genetic analysis of HLA-DRB1, -DQA1, -DQB1 and the insulin gene (INS) was
      performed in the Genetics of Kidneys in Diabetes (GoKinD) collection of DNA
      (European ancestry subset), which includes case patients with type 1 diabetes and
      nephropathy (n = 829) and control patients with type 1 diabetes but not
      nephropathy (n = 904). The availability of phenotypic and genotypic data on
      GoKinD participants allowed a detailed analysis of the association of these genes
      with diabetic nephropathy. RESULTS: Diabetic probands who were homozygous for HLA
      DRB1*04 were 50% less likely to have nephropathy than probands without any
      DRB1*04 alleles. In heterozygous carriers, a protective effect of this allele was
      not as clearly evident; the mode of inheritance therefore remains unclear. This
      association was seen in probands with both short (<28 years, P = 0.02) and long
      (>/=28 years, P = 0.0001) duration of diabetes. A1C, a marker of sustained
      hyperglycemia, was increased in control probands with normoalbuminuira, despite
      long-duration diabetes, from 7.2 to 7.3 to 7.7% with 0, 1, and 2 copies of the
      DRB1*04 allele, respectively. This result is consistent with a protective effect
      of DRB1*04 that may allow individuals to tolerate higher levels of hyperglycemia,
      as measured by A1C, without developing nephropathy. CONCLUSIONS: These data
      suggest that carriers of DRB1*04 are protected from some of the injurious
      hyperglycemic effects related to nephropathy. Interestingly, DRB1*04 appears to
      be both a risk allele for type 1 diabetes and a protective allele for
      nephropathy.

PMID- 18039813
TI  - Delayed recovery of cognitive function following hypoglycemia in adults with type
      1 diabetes: effect of impaired awareness of hypoglycemia.
AB  - OBJECTIVE: Recovery times of cognitive functions were examined after exposure to
      hypoglycemia in people with diabetes with and without impaired hypoglycemia
      awareness. RESEARCH DESIGN AND METHODS: A total of 36 subjects with type 1
      diabetes were studied (20 with normal hypoglycemia awareness [NHA] and 16 with
      impaired hypoglycemia awareness [IHA]). A hyperinsulinemic glucose clamp was used
      to lower blood glucose to 2.5 mmol/l (45 mg/dl) (hypoglycemia) for 1 h or to
      maintain blood glucose at 4.5 mmol/l (81 mg/dl) (euglycemia) on separate
      occasions. Cognitive tests were applied during each experimental condition and
      were repeated at 10- to 15-min intervals for 90 min after euglycemia had been
      restored. RESULTS: In the NHA group, performance was impaired on all cognitive
      tasks during hypoglycemia and remained impaired for up to 75 min on the choice
      reaction time (CRT) task (P = 0.03, eta(2) = 0.237). In the IHA group,
      performance did not deteriorate significantly during hypoglycemia. When all
      subjects were analyzed within the same general linear model, performance was
      impaired during hypoglycemia on all tasks. Significant impairment during recovery
      persisted for up to 40 min on the CRT task (P = 0.04, eta(2) = 0.125) with a
      significant glycemia-awareness interaction for CRT after one hour of hypoglycemia
      (P = 0.045, eta(2) = 0.124). Performance on the trail-making B task was impaired
      for up to 10 min after euglycemia was restored (P = 0.024, eta(2) = 0.158).
      CONCLUSIONS: Following hypoglycemia, the recovery time for different cognitive
      tasks varied considerably. In the IHA group, performance was not significantly
      impaired during hypoglycemia. The state of awareness of hypoglycemia may
      influence cognitive function during and after hypoglycemia.

PMID- 18039814
TI  - Receptor for advanced glycation end products (RAGEs) and experimental diabetic
      neuropathy.
AB  - OBJECTIVE: Heightened expression of the receptor for advanced glycation end
      products (RAGE) contributes to development of systemic diabetic complications,
      but its contribution to diabetic neuropathy is uncertain. We studied experimental
      diabetic neuropathy and its relationship with RAGE expression using
      streptozotocin-induced diabetic mice including a RAGE(-/-) cohort exposed to long
      term diabetes compared with littermates without diabetes. RESEARCH DESIGN AND
      METHODS: Structural indexes of neuropathy were addressed with serial (1, 3, 5,
      and 9 months of experimental diabetes) electrophysiological and quantitative
      morphometric analysis of dorsal root ganglia (DRG), peripheral nerve, and
      epidermal innervation. RAGE protein and mRNA levels in DRG, peripheral nerve, and
      epidermal terminals were assessed in WT and RAGE(-/-) mice, with and without
      diabetes. The correlation of RAGE activation with nuclear factor (NF)-kappaB and
      protein kinase C beta II (PKC beta II) protein and mRNA expression was also
      determined. RESULTS: Diabetic peripheral epidermal axons, sural axons, Schwann
      cells, and sensory neurons within ganglia developed dramatic and cumulative rises
      in RAGE mRNA and protein along with progressive electrophysiological and
      structural abnormalities. RAGE(-/-) mice had attenuated structural features of
      neuropathy after 5 months of diabetes. RAGE-mediated signaling pathway activation
      for NF-kappaB and PKC beta II pathways was most evident among Schwann cells in
      the DRG and peripheral nerve. CONCLUSIONS: In a long-term model of experimental
      diabetes resembling human diabetic peripheral neuropathy, RAGE expression in the
      peripheral nervous system rises cumulatively and relates to progressive
      pathological changes. Mice lacking RAGE have attenuated features of neuropathy
      and limited activation of potentially detrimental signaling pathways.

PMID- 18039815
TI  - Murine antithymocyte globulin therapy alters disease progression in NOD mice by a
      time-dependent induction of immunoregulation.
AB  - OBJECTIVE: Antilymphocyte serum can reverse overt type 1 diabetes in NOD mice;
      yet, the therapeutic parameters and immunological mechanisms underlying the
      ability for this agent to modulate autoimmune responses against beta-cells are
      unclear, forming the rationale for this investigation. RESEARCH DESIGN AND
      METHODS: A form of antilymphocyte serum, rabbit anti-mouse thymocyte globulin
      (mATG), was utilized in a variety of in vivo and in vitro settings, each for the
      purpose of defining the physiological, immunological, and metabolic activities of
      this agent, with particular focus on actions influencing development of type 1
      diabetes. RESULTS: We observed that mATG attenuates type 1 diabetes development
      in an age-dependent fashion, only proving efficacious at disease onset or in the
      late pre-diabetic phase (12 weeks of age). When provided at 12 weeks of age, mATG
      reversed pancreatic insulitis, improved metabolic responses to glucose challenge,
      and rapidly increased frequency of antigen-presenting cells in spleen and
      pancreatic lymph nodes. Surprisingly, mATG therapy dramatically increased, in an
      age-dependent fashion, the frequency and the functional activity of CD4(+)CD25(+)
      regulatory T-cells. Adoptive transfer/cotransfer studies of type 1 diabetes also
      support the concept that mATG treatment induces a stable and transferable
      immunomodulatory repertoire in vivo. CONCLUSIONS: These findings indicate that an
      induction of immunoregulation, rather than simple lymphocyte depletion,
      contributes to the therapeutic efficacy of antithymocyte globulin and suggest
      that time-dependent windows for the ability to delay or reverse type 1 diabetes
      exist based on the capacity to enhance the functional activity of regulatory T
      cells.

PMID- 18039816
TI  - A candidate type 2 diabetes polymorphism near the HHEX locus affects acute
      glucose-stimulated insulin release in European populations: results from the
      EUGENE2 study.
AB  - OBJECTIVE: In recent genome-wide association studies, two single nucleotide
      polymorphisms (SNPs) near the HHEX locus were shown to be more frequent in type 2
      diabetic patients than in control subjects. Based on HHEX's function during
      embryonic development of the ventral pancreas in mice, we investigated whether
      these SNPs affect beta-cell function in humans. RESEARCH DESIGN AND METHODS: A
      total of 854 nondiabetic subjects, collected from five European clinical centers,
      were genotyped for the HHEX SNPs rs1111875 and rs7923837 and thoroughly
      characterized by an oral glucose tolerance test (OGTT). To assess glucose
      stimulated insulin release, a subgroup of 758 subjects underwent an intravenous
      glucose tolerance test (IVGTT). RESULTS: SNPs rs1111875 and rs7923837 were not
      associated with anthropometric data (age, weight, height, BMI, body fat, and
      waist and hip circumference). After adjustment for center, family relationship,
      sex, age, and BMI, both SNPs were also not associated with glucose and insulin
      concentrations in the fasting state and during the OGTT or with measures of
      insulin sensitivity. Furthermore, HHEX SNP rs1111875 was not associated with
      insulin release during the IVGTT. By contrast, the minor A-allele of HHEX SNP
      rs7923837 was significantly associated with higher IVGTT-derived first-phase
      insulin release before and after appropriate adjustment (P = 0.013 and P = 0.014,
      respectively). CONCLUSIONS: A common genetic variation in the 3'-flanking region
      of the HHEX locus, i.e., SNP rs7923837, is associated with altered glucose
      stimulated insulin release. This SNP's major allele represents a risk allele for
      beta-cell dysfunction and, thus, might confer increased susceptibility of beta
      cells toward adverse environmental factors.

PMID- 18039817
TI  - The weak-acid preservative sorbic acid is decarboxylated and detoxified by a
      phenylacrylic acid decarboxylase, PadA1, in the spoilage mold Aspergillus niger.
AB  - Resistance to sorbic and cinnamic acids is mediated by a phenylacrylic acid
      decarboxylase (PadA1) in Aspergillus niger. A. niger DeltapadA1 mutants are
      unable to decarboxylate sorbic and cinnamic acids, and the MIC of sorbic acid
      required to inhibit spore germination was reduced by approximately 50% in
      DeltapadA1 mutants.

PMID- 18039818
TI  - Novel combination of atomic force microscopy and epifluorescence microscopy for
      visualization of leaching bacteria on pyrite.
AB  - Bioleaching of metal sulfides is an interfacial process comprising the
      interactions of attached bacterial cells and bacterial extracellular polymeric
      substances with the surface of a mineral sulfide. Such processes and the
      associated biofilms can be investigated at high spatial resolution using atomic
      force microscopy (AFM). Therefore, we visualized biofilms of the meso-acidophilic
      leaching bacterium Acidithiobacillus ferrooxidans strain A2 on the metal sulfide
      pyrite with a newly developed combination of AFM with epifluorescence microscopy
      (EFM). This novel system allowed the imaging of the same sample location with
      both instruments. The pyrite sample, as fixed on a shuttle stage, was transferred
      between AFM and EFM devices. By staining the bacterial DNA with a specific
      fluorescence dye, bacterial cells were labeled and could easily be distinguished
      from other topographic features occurring in the AFM image. AFM scanning in
      liquid caused deformation and detachment of cells, but scanning in air had no
      effect on cell integrity. In summary, we successfully demonstrate that the new
      microscopic system was applicable for visualizing bioleaching samples. Moreover,
      the combination of AFM and EFM in general seems to be a powerful tool for
      investigations of biofilms on opaque materials and will help to advance our
      knowledge of biological interfacial processes. In principle, the shuttle stage
      can be transferred to additional instruments, and combinations of AFM and EFM
      with other surface-analyzing devices can be proposed.

PMID- 18039819
TI  - Implications of rewiring bacterial quorum sensing.
AB  - Bacteria employ quorum sensing, a form of cell-cell communication, to sense
      changes in population density and regulate gene expression accordingly. This work
      investigated the rewiring of one quorum-sensing module, the lux circuit from the
      marine bacterium Vibrio fischeri. Steady-state experiments demonstrate that
      rewiring the network architecture of this module can yield graded, threshold, and
      bistable gene expression as predicted by a mathematical model. The experiments
      also show that the native lux operon is most consistent with a threshold, as
      opposed to a bistable, response. Each of the rewired networks yielded functional
      population sensors at biologically relevant conditions, suggesting that this
      operon is particularly robust. These findings (i) permit prediction of the
      behaviors of quorum-sensing operons in bacterial pathogens and (ii) facilitate
      forward engineering of synthetic gene circuits.

PMID- 18039820
TI  - Constraints on anaerobic respiration in the hyperthermophilic Archaea Pyrobaculum
      islandicum and Pyrobaculum aerophilum.
AB  - Pyrobaculum islandicum uses iron, thiosulfate, and elemental sulfur for anaerobic
      respiration, while Pyrobaculum aerophilum uses iron and nitrate; however, the
      constraints on these processes and their physiological mechanisms for iron and
      sulfur reduction are not well understood. Growth rates on sulfur compounds are
      highest at pH 5 to 6 and highly reduced (<-420-mV) conditions, while growth rates
      on nitrate and iron are highest at pH 7 to 9 and more-oxidized (>-210-mV)
      conditions. Growth on iron expands the known pH range of growth for both
      organisms. P. islandicum differs from P. aerophilum in that it requires direct
      contact with insoluble iron oxide for growth, it did not produce any
      extracellular compounds when grown on insoluble iron, and it lacked 2,6
      anthrahydroquinone disulfonate oxidase activity. Furthermore, iron reduction in
      P. islandicum appears to be completely independent of c-type cytochromes. Like
      that in P. aerophilum, NADH-dependent ferric reductase activity in P. islandicum
      increased significantly in iron-grown cultures relative to that in non-iron-grown
      cultures. Proteomic analyses showed that there were significant increases in the
      amounts of a putative membrane-bound thiosulfate reductase in P. islandicum
      cultures grown on thiosulfate relative to those in cultures grown on iron and
      elemental sulfur. This is the first evidence of this enzyme being used in either
      a hyperthermophile or an archaeon. Pyrobaculum arsenaticum and Pyrobaculum
      calidifontis also grew on Fe(III) citrate and insoluble iron oxide, but only P.
      arsenaticum could grow on insoluble iron without direct contact.

PMID- 18039823
TI  - The streptomycin-sulfadiazine-tetracycline antimicrobial resistance element of
      calf-adapted Escherichia coli is widely distributed among isolates from
      Washington state cattle.
AB  - Association of specific antimicrobial resistance patterns with unrelated
      selective traits has long been implicated in the maintenance of antimicrobial
      resistance in a population. Previously we demonstrated that Escherichia coli
      strains with a specific resistance pattern (resistant to streptomycin,
      sulfadiazine, and tetracycline [SSuT]) have a selective advantage in dairy calf
      intestinal environments and in the presence of a milk supplement commonly fed to
      the calves. In the present study we identified the sequence of the genetic
      element that confers the SSuT phenotype and show that this element is present in
      a genetically diverse group of E. coli isolates, as assessed by macrorestriction
      digestion and pulsed-field gel electrophoresis. This element was also found in E.
      coli isolates from 18 different cattle farms in Washington State. Using in vitro
      competition experiments we further demonstrated that SSuT strains from 17 of 18
      farms were able to outcompete pansusceptible strains. In a separate set of
      experiments, we were able to transfer the antimicrobial resistance phenotype by
      electroporation to a laboratory strain of E. coli (DH10B), making that new strain
      more competitive during in vitro competition with the parental DH10B strain.
      These data indicate that a relatively large genetic element conferring the SSuT
      phenotype is widely distributed in E. coli from cattle in Washington State.
      Furthermore, our results indicate that this element is responsible for
      maintenance of these traits owing to linkage to genetic traits that confer a
      selective advantage in the intestinal lumens of dairy calves.

PMID- 18039821
TI  - The native bacterioplankton community in the central baltic sea is influenced by
      freshwater bacterial species.
AB  - The Baltic Sea is one of the largest brackish environments on Earth. Despite
      extensive knowledge about food web interactions and pelagic ecosystem
      functioning, information about the bacterial community composition in the Baltic
      Sea is scarce. We hypothesized that due to the eutrophic low-salinity environment
      and the long water residence time (>5 years), the bacterioplankton community from
      the Baltic proper shows a native "brackish" composition influenced by both
      freshwater and marine phylotypes. The bacterial community composition in surface
      water (3-m depth) was examined at a single station throughout a full year.
      Denaturing gradient gel electrophoresis (DGGE) showed that the community
      composition changed over the year. Further, it indicated that at the four
      extensive samplings (16S rRNA gene clone libraries and bacterial isolates from
      low- and high-nutrient agar plates and seawater cultures), different bacterial
      assemblages associated with different environmental conditions were present.
      Overall, the sequencing of 26 DGGE bands, 160 clones, 209 plate isolates, and 9
      dilution culture isolates showed that the bacterial assemblage in surface waters
      of the central Baltic Sea was dominated by Bacteroidetes but exhibited a
      pronounced influence of typical freshwater phylogenetic groups within
      Actinobacteria, Verrucomicrobia, and Betaproteobacteria and a lack of typical
      marine taxa. This first comprehensive analysis of bacterial community composition
      in the central Baltic Sea points to the existence of an autochthonous estuarine
      community uniquely adapted to the environmental conditions prevailing in this
      brackish environment.

PMID- 18039822
TI  - Differential roles of poly-N-acetylglucosamine surface polysaccharide and
      extracellular DNA in Staphylococcus aureus and Staphylococcus epidermidis
      biofilms.
AB  - Staphylococcus aureus and Staphylococcus epidermidis are major human pathogens of
      increasing importance due to the dissemination of antibiotic-resistant strains.
      Evidence suggests that the ability to form matrix-encased biofilms contributes to
      the pathogenesis of S. aureus and S. epidermidis. In this study, we investigated
      the functions of two staphylococcal biofilm matrix polymers: poly-N
      acetylglucosamine surface polysaccharide (PNAG) and extracellular DNA (ecDNA). We
      measured the ability of a PNAG-degrading enzyme (dispersin B) and DNase I to
      inhibit biofilm formation, detach preformed biofilms, and sensitize biofilms to
      killing by the cationic detergent cetylpyridinium chloride (CPC) in a 96-well
      microtiter plate assay. When added to growth medium, both dispersin B and DNase I
      inhibited biofilm formation by both S. aureus and S. epidermidis. Dispersin B
      detached preformed S. epidermidis biofilms but not S. aureus biofilms, whereas
      DNase I detached S. aureus biofilms but not S. epidermidis biofilms. Similarly,
      dispersin B sensitized S. epidermidis biofilms to CPC killing, whereas DNase I
      sensitized S. aureus biofilms to CPC killing. We concluded that PNAG and ecDNA
      play fundamentally different structural roles in S. aureus and S. epidermidis
      biofilms.

PMID- 18039824
TI  - Complete genomic sequence of bacteriophage phiEcoM-GJ1, a novel phage that has
      myovirus morphology and a podovirus-like RNA polymerase.
AB  - The complete genome of phiEcoM-GJ1, a lytic phage that attacks porcine
      enterotoxigenic Escherichia coli of serotype O149:H10:F4, was sequenced and
      analyzed. The morphology of the phage and the identity of the structural proteins
      were also determined. The genome consisted of 52,975 bp with a G+C content of 44%
      and was terminally redundant and circularly permuted. Seventy-five potential open
      reading frames (ORFs) were identified and annotated, but only 29 possessed
      homologs. The proteins of five ORFs showed homology with proteins of phages of
      the family Myoviridae, nine with proteins of phages of the family Podoviridae,
      and six with proteins of phages of the family Siphoviridae. ORF 1 encoded a T7
      like single-subunit RNA polymerase and was preceded by a putative E. coli
      sigma(70)-like promoter. Nine putative phage promoters were detected throughout
      the genome. The genome included a tRNA gene of 95 bp that had a putative 18-bp
      intron. The phage morphology was typical of phages of the family Myoviridae, with
      an icosahedral head, a neck, and a long contractile tail with tail fibers. The
      analysis shows that phiEcoM-GJ1 is unique, having the morphology of the
      Myoviridae, a gene for RNA polymerase, which is characteristic of phages of the
      T7 group of the Podoviridae, and several genes that encode proteins with homology
      to proteins of phages of the family Siphoviridae.

PMID- 18039825
TI  - Genome-scale genotype-phenotype matching of two Lactococcus lactis isolates from
      plants identifies mechanisms of adaptation to the plant niche.
AB  - Lactococcus lactis is a primary constituent of many starter cultures used for the
      manufacturing of fermented dairy products, but the species also occurs in various
      nondairy niches such as (fermented) plant material. Three genome sequences of L.
      lactis dairy strains (IL-1403, SK11, and MG1363) are publicly available. An
      extensive molecular and phenotypic diversity analysis was now performed on two L.
      lactis plant isolates. Diagnostic sequencing of their genomes resulted in over
      2.5 Mb of sequence for each strain. A high synteny was found with the genome of
      L. lactis IL-1403, which was used as a template for contig mapping and locating
      deletions and insertions in the plant L. lactis genomes. Numerous genes were
      identified that do not have homologs in the published genome sequences of dairy
      L. lactis strains. Adaptation to growth on substrates derived from plant cell
      walls is evident from the presence of gene sets for the degradation of complex
      plant polymers such as xylan, arabinan, glucans, and fructans but also for the
      uptake and conversion of typical plant cell wall degradation products such as
      alpha-galactosides, beta-glucosides, arabinose, xylose, galacturonate,
      glucuronate, and gluconate. Further niche-specific differences are found in genes
      for defense (nisin biosynthesis), stress response (nonribosomal peptide synthesis
      and various transporters), and exopolysaccharide biosynthesis, as well as the
      expected differences in various mobile elements such as prophages, plasmids,
      restriction-modification systems, and insertion sequence elements. Many of these
      genes were identified for the first time in Lactococcus lactis. In most cases
      good correspondence was found with the phenotypic characteristics of these two
      strains.

PMID- 18039826
TI  - Efficient antibody production upon suppression of O mannosylation in the yeast
      Ogataea minuta.
AB  - When antibodies were expressed in the methylotrophic yeast Ogataea minuta, we
      found that abnormal O mannosylation occurred in the secreted antibody. Yeast
      specific O mannosylation is initiated by the addition of mannose at serine (Ser)
      or threonine (Thr) residues in the endoplasmic reticulum via protein O
      mannosyltransferase (Pmt) activity. To suppress the addition of O-linked sugar
      chains on antibodies, we examined the possibility of inhibiting Pmt activity by
      the addition of a Pmt inhibitor during cultivation. The Pmt inhibitor was found
      to partially suppress the O mannosylation on the antibodies. Surprisingly, the
      suppression of O mannosylation was associated with an increased amount of
      assembled antibody (H2L2) and enhanced the antigen-binding activity of the
      secreted antibody. In this study, we demonstrated the expression of human
      antibody in O. minuta and elucidated the relationship between O mannosylation and
      antibody production in yeast.

PMID- 18039827
TI  - Characterization of the structural gene encoding nisin F, a new lantibiotic
      produced by a Lactococcus lactis subsp. lactis isolate from freshwater catfish
      (Clarias gariepinus).
AB  - Lactococcus lactis F10, isolated from freshwater catfish, produces a bacteriocin
      (BacF) active against Staphylococcus aureus, Staphylococcus carnosus,
      Lactobacillus curvatus, Lactobacillus plantarum, and Lactobacillus reuteri. The
      operon encoding BacF is located on a plasmid. Sequencing of the structural gene
      revealed no homology to other nisin genes. Nisin F is described.

PMID- 18039828
TI  - The BaeSR two-component regulatory system mediates resistance to condensed
      tannins in Escherichia coli.
AB  - The gene expression profiles of Escherichia coli strains grown anaerobically with
      or without Acacia mearnsii (black wattle) extract were compared to identify
      tannin resistance strategies. The cell envelope stress protein gene spy and the
      multidrug transporter-encoding operon mdtABCD, both under the control of the
      BaeSR two-component regulatory system, were significantly up-regulated in the
      presence of tannins. BaeSR mutants were more tannin sensitive than their wild
      type counterparts.

PMID- 18039829
TI  - Subfossil 16S rRNA gene sequences of green sulfur bacteria in the Black Sea and
      their implications for past photic zone anoxia.
AB  - The Black Sea is the largest extant anoxic water body on Earth. Its oxic-anoxic
      boundary is located at a depth of 100 m and is populated by a single phylotype of
      marine green sulfur bacteria. This organism, Chlorobium sp. strain BS-1, is
      extraordinarily low light adapted and can therefore serve as an indicator of deep
      photic zone anoxia (A. K. Manske, J. Glaeser, M. M. M. Kuypers, and J. Overmann,
      Appl. Environ. Microbiol. 71:8049-8060, 2005). In the present study, two sediment
      cores were retrieved from the bottom of the Black Sea at depths of 2,006 and
      2,162 m and were analyzed for the presence of subfossil DNA sequences of BS-1
      using ancient-DNA methodology. Using optimized cultivation media, viable cells of
      the BS-1 phylotype were detected only at the sediment surface and not in deeper
      layers. In contrast, green sulfur bacterial 16S rRNA gene fragments were
      amplified from all the sediment layers investigated, including turbidites. After
      separation by denaturing gradient gel electrophoresis and sequencing, 14
      different sequence types were distinguished. The sequence of BS-1 represented
      only a minor fraction of the amplification products and was found in 6 of 22 and
      4 of 26 samples from the 2,006- and 2,162-m stations, respectively. Besides the
      sequences of BS-1, three additional phylotypes of the marine clade of green
      sulfur bacteria were detected. However, the majority of sequences clustered with
      groups from freshwater habitats. Our results suggest that a considerable fraction
      of green sulfur bacterial chemofossils did not originate in a low-light marine
      chemocline environment and therefore were likely to have an allochthonous origin.
      Thus, analysis of subfossil DNA sequences permits a more differentiated
      interpretation and reconstruction of past environmental conditions if specific
      chemofossils of stenoec species, like Chlorobium sp. strain BS-1, are employed.

PMID- 18039830
TI  - Regulatory Interactions among adhesin gene systems of uropathogenic Escherichia
      coli.
AB  - Uropathogenic Escherichia coli strain J96 carries multiple determinants for
      fimbrial adhesins. The regulatory protein PapB of P fimbriae has previously been
      implicated in potential coregulatory events. The focB gene of the F1C fimbria
      determinant is highly homologous to papB; the translated sequences share 81%
      identity. In this study we investigated the role of PapB and FocB in regulation
      of the F1C fimbriae. By using gel mobility shift assays, we showed that FocB
      binds to sequences in both the pap and foc operons in a somewhat different manner
      than PapB. The results of both in vitro cross-linking and in vivo oligomerization
      tests indicated that FocB could function in an oligomeric fashion. Furthermore,
      our results suggest that PapB and FocB can form heterodimers and that these
      complexes can repress expression of the foc operon. The effect of FocB on
      expression of type 1 fimbriae was also tested. Taken together, the results that
      we present expand our knowledge about a regulatory network for different adhesin
      gene systems in uropathogenic E. coli and suggest a hierarchy for expression of
      the fimbrial adhesins.

PMID- 18039831
TI  - Molecular basis of commensalism in the urinary tract: low virulence or virulence
      attenuation?
AB  - In some patients, Escherichia coli strains establish significant bacteriuria
      without causing symptoms of urinary tract infection (UTI). These asymptomatic
      bacteriuria (ABU) strains have been shown to express fewer virulence factors than
      the uropathogenic E. coli (UPEC) strains that cause severe, symptomatic UTI.
      Paradoxically, ABU strains carry many typical UPEC virulence genes, and the
      molecular basis of their low virulence therefore remains unclear. This study
      examined whether ABU strains might evolve from UPEC by genome loss and virulence
      gene attenuation. The presence of conserved E. coli K-12 genes was examined using
      an E. coli K-12 strain MG1655-specific DNA array and the distribution of UPEC
      virulence-related genes was examined with the E. coli pathoarray. Two groups of
      strains could be distinguished. Several ABU strains were shown by multilocus
      sequence typing and by comparative genomic analyses to be related to UPEC but to
      have smaller genome sizes. There were significant alterations in essential
      virulence genes, including reductive evolution by point mutations, DNA
      rearrangements, and deletions. Other strains were unrelated to UPEC and lacked
      most of the virulence-associated genes. The results suggest that some ABU strains
      arise from virulent strains by attenuation of virulence genes while others are
      nonvirulent and resemble commensal strains. We propose that virulence attenuation
      might constitute a general mechanism for mucosal pathogens to evolve toward
      commensalism.

PMID- 18039832
TI  - MyD88 signaling contributes to early pulmonary responses to Aspergillus
      fumigatus.
AB  - Toll-like receptors and the beta-glucan receptor, dectin-1, mediate macrophage
      inflammatory responses to Aspergillus fumigatus through MyD88-dependent and 
      independent signaling mechanisms; however, pulmonary inflammatory responses in
      MyD88-deficient mice challenged with A. fumigatus are poorly defined. The role of
      MyD88 signaling in early pulmonary inflammation and fungal clearance was
      evaluated in C57BL/6J wild-type (WT) and MyD88-deficient (MyD88-/-) mice. Early
      (<48 h) after infection, MyD88-/- mice had higher fungal burdens than those of WT
      mice, although fungal burdens rapidly declined (>72 h) in both. MyD88-/- mice had
      less consolidated inflammation, with fewer NK cells, in lung tissue early (24 h)
      after infection than did WT mice. At the latter time point, MyD88-/- mouse lungs
      were characterized by a large amount of necrotic cellular debris and fibrin,
      while WT lungs had organized inflammation. Although there were equivalent numbers
      of macrophages in WT and MyD88-/- mouse lung tissues, MyD88-/- cells demonstrated
      delayed uptake of green fluorescent protein-expressing A. fumigatus (GFP-Af293);
      histologically, MyD88-/- mouse lungs had more hyphal invasion of terminal airways
      and vessels, the appearance of bronchiolar epithelial cell necrosis, and
      necrotizing vasculitis. MyD88-/- lung homogenates contained comparatively
      decreased amounts of interleukin-1beta (IL-1beta), IL-6, KC, and gamma interferon
      and paradoxically increased amounts of tumor necrosis factor alpha and macrophage
      inflammatory protein 1alpha. These data indicate that the MyD88-dependent pathway
      mediates acute pulmonary fungal clearance, inflammation, and tissue injury very
      early after infection. Resolution of abnormalities within a 3-day window
      demonstrates the importance of redundant signaling pathways in mediating
      pulmonary inflammatory responses to fungi.

PMID- 18039833
TI  - Intranasal interleukin-12 therapy inhibits Mycoplasma pneumoniae clearance and
      sustains airway obstruction in murine pneumonia.
AB  - Mycoplasma pneumoniae is a leading cause of pneumonia and is associated with
      asthma. Evidence links M. pneumoniae respiratory disease severity with
      interleukin-12 (IL-12) concentrations in respiratory secretions. We evaluated the
      effects of IL-12 therapy on microbiologic, inflammatory, and pulmonary function
      indices of M. pneumoniae pneumonia in mice. BALB/c mice were inoculated with M.
      pneumoniae or SP4 broth. Mice were treated with intranasal IL-12 or placebo daily
      for 8 days, starting on day 1 after inoculation. Mice were evaluated at baseline
      and on days 1, 3, 6, and 8 after therapy. Outcome variables included quantitative
      bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score
      (HPS), BAL cytokine concentrations determined by enzyme-linked immunosorbent
      assay (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], IL
      1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, and granulocyte-macrophage colony
      stimulating factor), and plethysmography, both before and after methacholine
      treatment. M. pneumoniae-infected mice treated with IL-12 (MpIL12 mice) were
      found to have significantly higher BAL M. pneumoniae concentrations than those of
      M. pneumoniae-infected mice treated with placebo (MpP mice) (P < 0.001). MpIL12
      mice had higher BAL concentrations of IL-12, IFN-gamma, TNF-alpha, and IL-6, with
      differences in IL-12 and IFN-gamma concentrations reaching statistical
      significance (P < 0.001). Airway obstruction was statistically elevated in MpIL12
      mice compared to that in MpP mice (P = 0.048), while airway hyperreactivity was
      also elevated in MpIL12 mice but did not reach statistical significance (P =
      0.081). Lung parenchymal pneumonia subscores were significantly higher in MpIL12
      mice (P < 0.001), but no difference was found for overall HPS, even though a
      strong trend was noticed (P = 0.051). Treatment of experimental M. pneumoniae
      pneumonia with intranasal IL-12 was associated with more severe pulmonary disease
      and less rapid microbiologic and histological resolution.

PMID- 18039834
TI  - Modulation of pulmonary dendritic cell function during mycobacterial infection.
AB  - We have previously reported that during mycobacterial infection, naive CD4(+) T
      cell activation is enhanced in the lungs. We investigated the role of chemokine
      receptor CCR7 and its ligands in the ability of CD11c(+) lung dendritic cells
      (DCs) to activate naive CD4(+) T cells during pulmonary infection with
      Mycobacterium bovis bacillus Calmette-Guerin (BCG). BCG infection resulted in the
      accumulation and maturation in the lungs of DCs that persisted as the
      mycobacterial burden declined. Lung DCs from infected mice expressed more major
      histocompatibility complex class II (MHC-II) than those from uninfected mice.
      CCR7 expression levels on lung DCs were comparable among uninfected and infected
      mice. The gene expression of the CCR7 ligand CCL19 progressively increased
      throughout BCG infection, and its expression was MyD88 dependent. CD11c(+) lung
      cells from BCG-infected mice activated ovalbumin (OVA)-specific naive CD4(+) T
      cells more than CD11c(+) lung cells from uninfected mice. Interestingly, during
      peak mycobacterial infection, CD11c(hi) MHC(hi) lung DCs had slightly decreased
      chemotaxis toward the CCR7 ligand CCL21 and less efficiency in activating naive
      CD4(+) T cells than DCs from mice during late-stage infection, when few bacilli
      are found in the lung. These findings suggest that during BCG infection, the
      inflammation and sustained expression of CCL19 result in the recruitment,
      activation, and retention in the lung of DCs that can activate naive CD4(+) T
      cells in situ.

PMID- 18039835
TI  - Profiling bovine antibody responses to Mycobacterium avium subsp.
      paratuberculosis infection by using protein arrays.
AB  - With the genome sequence of Mycobacterium avium subsp. paratuberculosis
      determined, technologies are now being developed for construction of protein
      arrays to detect the presence of antibodies against M. avium subsp.
      paratuberculosis in host serum. The power of this approach is that it enables a
      direct comparison of M. avium subsp. paratuberculosis proteins to each other in
      relation to their immunostimulatory capabilities. In this study, 93 recombinant
      proteins, produced in Escherichia coli, were arrayed and spotted onto
      nitrocellulose. These proteins include unknown hypothetical proteins and cell
      surface proteins as well as proteins encoded by large sequence polymorphisms
      present uniquely in M. avium subsp. paratuberculosis. Also included were
      previously reported or known M. avium subsp. paratuberculosis antigens to serve
      as a frame of reference. Sera from healthy control cattle (n = 3) and cattle
      infected with either M. avium subsp. avium and Mycobacterium bovis were exposed
      to the array to identify nonspecific or cross-reactive epitopes. These data
      demonstrated a degree of cross-reactivity with the M. avium subsp. avium proteins
      that was higher than the degree of cross-reactivity with the more distantly
      related M. bovis proteins. Finally, sera from naturally infected cattle (n = 3)
      as well as cattle experimentally infected with M. avium subsp. paratuberculosis
      (n = 3) were used to probe the array to identify antigens in the context of
      Johne's disease. Three membrane proteins were the most strongly detected in all
      serum samples, and they included an invasion protein, an ABC peptide transport
      permease, and a putative GTPase protein. This powerful combination of genomic
      information, molecular tools, and immunological assays has enabled the
      identification of previously unknown antigens of M. avium subsp.
      paratuberculosis.

PMID- 18039836
TI  - Pneumococcal virulence gene expression and host cytokine profiles during
      pathogenesis of invasive disease.
AB  - Pneumococcal disease continues to account for significant morbidity and mortality
      worldwide. For the development of novel prophylactic and therapeutic strategies
      against the disease spectrum, a complete understanding of pneumococcal behavior
      in vivo is necessary. We evaluated the expression patterns of the proven and
      putative virulence factor genes adcR, cbpA, cbpD, cbpG, cpsA, nanA, pcpA, piaA,
      ply, psaA, pspA, and spxB after intranasal infection of CD1 mice with serotype 2,
      4, and 6A pneumococci by real-time reverse transcription-PCR. Simultaneous gene
      expression patterns of selected host immunomodulatory molecules, CCL2, CCL5,
      CD54, CXCL2, interleukin-6, and tomor necrosis factor alpha, were also
      investigated. We show that pneumococcal virulence genes are differentially
      expressed in vivo, with some genes demonstrating niche- and serotype-specific
      differential expression. The in vivo expression patterns could not be attributed
      to in vitro differences in expression of the genes in transparent and opaque
      variants of the three strains. The host molecules were significantly upregulated,
      especially in the lungs, blood, and brains of mice. The pneumococcal-gene
      expression patterns support their ascribed roles in pathogenesis, providing
      insight into which protein combinations might be more appropriate as vaccine
      antigens against invasive disease. This is the first simultaneous comparison of
      bacterial- and host gene expression in the same animal during pathogenesis. The
      strategy provides a platform for prospective evaluation of interaction kinetics
      between invading pneumococci and human patients in culture-positive cases and
      should be feasible in other infection models.

PMID- 18039837
TI  - Elucidating the function of an ancient NF-kappaB p100 homologue, CrRelish, in
      antibacterial defense.
AB  - The family of NF-kappaB transcription factors essentially regulates immune
      related gene expression. Recently, we isolated and characterized the classical NF
      kappaB/inhibitor kappaB (IkappaB) homologues from a "living fossil," the
      horseshoe crab, Carcinoscorpius rotundicauda. Interestingly, this ancient species
      also harbors another class I NF-kappaB p100 homologue, C. rotundicauda Relish
      (CrRelish). Similar to Drosophila Relish and the mammalian p100, CrRelish
      contains both the Rel-homology domains (RHD) and the IkappaB-like domain. In this
      study, we found that the RHD of CrRelish can recognize horseshoe crab and human
      kappaB response elements and activate the downstream reporter in vitro, thereby
      suggesting the evolutionary conservation of this molecule. Pseudomonas aeruginosa
      infection transcriptionally upregulates CrRelish, which exhibits a dynamic
      protein profile over the time course of infection. Surprisingly, secondary
      infection reinduced an upsurge in CrRelish protein expression to a level which
      overrode the protein degradation at 12 h postinfection. These observations
      strongly suggest the involvement of CrRelish in antibacterial defense. Secondary
      infection causes (i) the maintenance of a favorable expression-competent sequence
      context of the CrRelish gene and/or (ii) the derepression or stabilization of the
      CrRelish transcript resulting from the primary infection to enable the more rapid
      expression and accumulation of the CrRelish protein, reflecting apparent
      signal/immune priming in a repeated infection.

PMID- 18039838
TI  - The opportunistic human pathogenic fungus Aspergillus fumigatus evades the host
      complement system.
AB  - The opportunistic human pathogenic fungus Aspergillus fumigatus causes severe
      systemic infections and is a major cause of fungal infections in
      immunocompromised patients. A. fumigatus conidia activate the alternative pathway
      of the complement system. In order to assess the mechanisms by which A. fumigatus
      evades the activated complement system, we analyzed the binding of host
      complement regulators to A. fumigatus. The binding of factor H and factor H-like
      protein 1 (FHL-1) from human sera to A. fumigatus conidia was shown by adsorption
      assays and immunostaining. In addition, factor H-related protein 1 (FHR-1) bound
      to conidia. Adsorption assays with recombinant factor H mutants were used to
      localize the binding domains. One binding region was identified within N-terminal
      short consensus repeats (SCRs) 1 to 7 and a second one within C-terminal SCR 20.
      Plasminogen was identified as the fourth host regulatory molecule that binds to
      A. fumigatus conidia. In contrast to conidia, other developmental stages of A.
      fumigatus, like swollen conidia or hyphae, did not bind to factor H, FHR-1, FHL
      1, and plasminogen, thus indicating the developmentally regulated expression of
      A. fumigatus surface ligands. Both factor H and plasminogen maintained regulating
      activity when they were bound to the conidial surface. Bound factor H acted as a
      cofactor to the factor I-mediated cleavage of C3b. Plasminogen showed proteolytic
      activity when activated to plasmin by urokinase-type plasminogen activator. These
      data show that A. fumigatus conidia bind to complement regulators, and these
      bound host regulators may contribute to evasion of a host complement attack.

PMID- 18039839
TI  - A stage-specific factor confers Fab-7 boundary activity during early
      embryogenesis in Drosophila.
AB  - The Fab-7 boundary is required to ensure that the iab-6 and iab-7 cis-regulatory
      domains in the Drosophila Bithorax complex can function autonomously. Though Fab
      7 functions as a boundary from early embryogenesis through to the adult stage,
      this constitutive boundary activity depends on subelements whose activity is
      developmentally restricted. In the studies reported here, we have identified a
      factor, called early boundary activity (Elba), that confers Fab-7 boundary
      activity during early embryogenesis. The Elba factor binds to a recognition
      sequence within a Fab-7 subelement that has enhancer-blocking activity during
      early embryogenesis, but not during mid-embryogenesis or in the adult. We found
      that the Elba factor is present in early embryos but largely disappears during
      mid-embryogenesis. We show that mutations in the Elba recognition sequence that
      eliminate Elba binding in nuclear extracts disrupt the early boundary activity of
      the Fab-7 subelement. Conversely, we find that early boundary activity can be
      reconstituted by multimerizing the Elba recognition site.

PMID- 18039840
TI  - Alternative mechanisms by which mediator subunit MED1/TRAP220 regulates
      peroxisome proliferator-activated receptor gamma-stimulated adipogenesis and
      target gene expression.
AB  - Mediator is a general coactivator complex connecting transcription activators and
      RNA polymerase II. Recent work has shown that the nuclear receptor-interacting
      MED1/TRAP220 subunit of Mediator is required for peroxisome proliferator
      activated receptor gamma (PPARgamma)-stimulated adipogenesis of mouse embryonic
      fibroblasts (MEFs). However, the molecular mechanisms remain undefined. Here, we
      show an intracellular PPARgamma-Mediator interaction that requires the two LXXLL
      nuclear receptor recognition motifs on MED1/TRAP220 and, furthermore, we show
      that the intact LXXLL motifs are essential for optimal PPARgamma function in a
      reconstituted cell-free transcription system. Surprisingly, a conserved N
      terminal region of MED1/TRAP220 that lacks the LXXLL motifs but gets incorporated
      into Mediator fully supports PPARgamma-stimulated adipogenesis. Moreover, in
      undifferentiated MEFs, MED1/TRAP220 is dispensable both for PPARgamma-mediated
      target gene activation and for recruitment of Mediator to a PPAR response element
      on the aP2 target gene promoter. However, PPARgamma shows significantly reduced
      transcriptional activity in cells deficient for a subunit (MED24/TRAP100)
      important for the integrity of the Mediator complex, indicating a general
      Mediator requirement for PPARgamma function. These results indicate that there is
      a conditional requirement for MED1/TRAP220 and that a direct interaction between
      PPARgamma and Mediator through MED1/TRAP220 is not essential either for PPARgamma
      stimulated adipogenesis or for PPARgamma target gene expression in cultured
      fibroblasts. As Mediator is apparently essential for PPARgamma transcriptional
      activity, our data indicate the presence of alternative mechanisms for Mediator
      recruitment, possibly through intermediate cofactors or other cofactors that are
      functionally redundant with MED1/TRAP220.

PMID- 18039841
TI  - Epigenetic and phenotypic consequences of a truncation disrupting the imprinted
      domain on distal mouse chromosome 7.
AB  - The distal end of mouse chromosome 7 (Chr 7) contains a large cluster of
      imprinted genes. In this region two cis-acting imprinting centers, IC1 (H19 DMR)
      and IC2 (KvDMR1), define proximal and distal subdomains, respectively. To assess
      the functional independence of IC1 in the context of Chr 7, we developed a
      recombinase-mediated chromosome truncation strategy in embryonic stem cells and
      generated a terminal deletion allele, DelTel7, with a breakpoint in between the
      two subdomains. We obtained germ line transmission of the truncated Chr 7 and
      viable paternal heterozygotes, confirming the absence of developmentally required
      paternally expressed genes distal of Ins2. Conversely, maternal transmission of
      DelTel7 causes a midgestational lethality, consistent with loss of maternally
      expressed genes in the IC2 subdomain. Expression and DNA methylation analyses on
      DelTel7 heterozygotes demonstrate the independent imprinting of IC1 in absence of
      the entire IC2 subdomain. The evolutionarily conserved linkage between the
      subdomains is therefore not required for IC1 imprinting on Chr 7. Importantly,
      the developmental phenotype of maternal heterozygotes is rescued fully by a
      paternally inherited deletion of IC2. Thus, all the imprinted genes located in
      the region and required for normal development are silenced by an IC2-dependent
      mechanism on the paternal allele.

PMID- 18039842
TI  - G9a histone methyltransferase contributes to imprinting in the mouse placenta.
AB  - Whereas DNA methylation is essential for genomic imprinting, the importance of
      histone methylation in the allelic expression of imprinted genes is unclear.
      Imprinting control regions (ICRs), however, are marked by histone H3-K9
      methylation on their DNA-methylated allele. In the placenta, the paternal
      silencing along the Kcnq1 domain on distal chromosome 7 also correlates with the
      presence of H3-K9 methylation, but imprinted repression at these genes is
      maintained independently of DNA methylation. To explore which histone
      methyltransferase (HMT) could mediate the allelic H3-K9 methylation on distal
      chromosome 7, and at ICRs, we generated mouse conceptuses deficient for the SET
      domain protein G9a. We found that in the embryo and placenta, the differential
      DNA methylation at ICRs and imprinted genes is maintained in the absence of G9a.
      Accordingly, in embryos, imprinted gene expression was unchanged at the domains
      analyzed, in spite of a global loss of H3-K9 dimethylation (H3K9me2). In
      contrast, the placenta-specific imprinting of genes on distal chromosome 7 is
      impaired in the absence of G9a, and this correlates with reduced levels of
      H3K9me2 and H3K9me3. These findings provide the first evidence for the
      involvement of an HMT and suggest that histone methylation contributes to
      imprinted gene repression in the trophoblast.

PMID- 18039843
TI  - Glucose phosphorylation and mitochondrial binding are required for the protective
      effects of hexokinases I and II.
AB  - Alterations in glucose metabolism have been demonstrated for diverse disorders
      ranging from heart disease to cancer. The first step in glucose metabolism is
      carried out by the hexokinase (HK) family of enzymes. HKI and II can bind to
      mitochondria through their N-terminal hydrophobic regions, and their
      overexpression in tissue culture protects against cell death. In order to
      determine the relative contributions of mitochondrial binding and glucose
      phosphorylating activities of HKs to their overall protective effects, we
      expressed full-length HKI and HKII, their truncated proteins lacking the
      mitochondrial binding domains, and catalytically inactive proteins in tissue
      culture. The overexpression of full-length proteins resulted in protection
      against cell death, decreased levels of reactive oxygen species, and possibly
      inhibited mitochondrial permeability transition in response to H(2)O(2). However,
      the truncated and mutant proteins exerted only partial effects. Similar results
      were obtained with primary neonatal rat cardiomyocytes. The HK proteins also
      resulted in an increase in the phosphorylation of voltage-dependent anion channel
      (VDAC) through a protein kinase Cepsilon (PKCepsilon)-dependent pathway. These
      results suggest that both glucose phosphorylation and mitochondrial binding
      contribute to the protective effects of HKI and HKII, possibly through VDAC
      phosphorylation by PKCepsilon.

PMID- 18039844
TI  - Inactivation of the polycomb group protein Ring1B unveils an antiproliferative
      role in hematopoietic cell expansion and cooperation with tumorigenesis
      associated with Ink4a deletion.
AB  - Polycomb group (PcG) proteins act as positive regulators of cell proliferation.
      Ring1B is a PcG gene essential for embryonic development, but its contribution to
      cell turnover in regenerating tissues in not known. Here, we have generated a
      conditional mouse mutant line to study the Ring1B role in adult hematopoiesis.
      Mutant mice developed a hypocellular bone marrow that paradoxically contained an
      enlarged, hyperproliferating compartment of immature cells, with an intact
      differentiation potential. These alterations were associated with differential
      upregulation of cyclin D2, which occurred in all mutant bone marrow cells, and of
      p16(Ink4a), observed only in the differentiated compartment. Concurrent
      inactivation of Ink4a rescued the defective proliferation of maturing cells but
      did not affect the hyperproliferative activity of progenitors and resulted in a
      shortening of the onset of lymphomas induced by Ink4a inactivation. These data
      show that Ring1B restricts the progenitors' proliferation and promotes the
      proliferation of their maturing progeny by selectively altering the expression
      pattern of cell cycle regulators along hematopoietic differentiation. The novel
      antiproliferative role of Ring1B's downregulation of a cell cycle activator may
      play an important role in the tight control of hematopoietic cell turnover.

PMID- 18039845
TI  - Primary ciliary dyskinesia in mice lacking the novel ciliary protein Pcdp1.
AB  - Primary ciliary dyskinesia (PCD) results from ciliary dysfunction and is commonly
      characterized by sinusitis, male infertility, hydrocephalus, and situs inversus.
      Mice homozygous for the nm1054 mutation develop phenotypes associated with PCD.
      On certain genetic backgrounds, homozygous mutants die perinatally from severe
      hydrocephalus, while mice on other backgrounds have an accumulation of mucus in
      the sinus cavity and male infertility. Mutant sperm lack mature flagella, while
      respiratory epithelial cilia are present but beat at a slower frequency than wild
      type cilia. Transgenic rescue demonstrates that the PCD in nm1054 mutants results
      from the loss of a single gene encoding the novel primary ciliary dyskinesia
      protein 1 (Pcdp1). The Pcdp1 gene is expressed in spermatogenic cells and motile
      ciliated epithelial cells. Immunohistochemistry shows that Pcdp1 protein
      localizes to sperm flagella and the cilia of respiratory epithelial cells and
      brain ependymal cells in both mice and humans. This study demonstrates that Pcdp1
      plays an important role in ciliary and flagellar biogenesis and motility, making
      the nm1054 mutant a useful model for studying the molecular genetics and
      pathogenesis of PCD.

PMID- 18039846
TI  - Promoter region-specific histone incorporation by the novel histone chaperone
      ANP32B and DNA-binding factor KLF5.
AB  - Regulation of chromatin in eukaryotic transcription requires histone-modifying
      enzymes, nucleosome remodeling complexes, and histone chaperones. Specific
      regulation of histone incorporation/eviction by histone chaperones on the
      promoter (e.g., region specific) is still poorly understood. In the present
      study, we show that direct and functional interaction of histone chaperone and
      DNA-binding transcription factor leads to promoter region-specific histone
      incorporation and inhibition of histone acetylation. We report here that the DNA
      binding transcription factor Kruppel-like factor 5 (KLF5) interacts with the
      novel histone chaperone acidic nuclear phosphoprotein 32B (ANP32B), leading to
      transcriptional repression of a KLF5-downstream gene. We further show that
      recruitment of ANP32B onto the promoter region requires KLF5 and results in
      promoter region-specific histone incorporation and inhibition of histone
      acetylation by ANP32B. Extracellular stimulus (e.g., phorbol ester) regulates
      this mechanism in the cell. Collectively, we have identified a novel histone
      chaperone, ANP32B, and through analysis of the actions of this factor show a new
      mechanism of promoter region-specific transcriptional regulation at the chromatin
      level as mediated by the functional interaction between histone chaperone and DNA
      binding transcription factor.

PMID- 18039847
TI  - Myeloid translocation gene family members associate with T-cell factors (TCFs)
      and influence TCF-dependent transcription.
AB  - Canonical Wnt signaling is mediated by a molecular "switch" that regulates the
      transcriptional properties of the T-cell factor (TCF) family of DNA-binding
      proteins. Members of the myeloid translocation gene (MTG) family of
      transcriptional corepressors are frequently disrupted by chromosomal
      translocations in acute myeloid leukemia, whereas MTG16 may be inactivated in up
      to 40% of breast cancer and MTG8 is a candidate cancer gene in colorectal
      carcinoma. Genetic studies imply that this corepressor family may function in
      stem cells. Given that mice lacking Myeloid Translocation Gene Related-1 (Mtgr1)
      fail to maintain the secretory lineage in the small intestine, we surveyed
      transcription factors that might recruit Mtgr1 in intestinal stem cells or
      progenitor cells and found that MTG family members associate specifically with
      TCF4. Coexpression of beta-catenin disrupted the association between these
      corepressors and TCF4. Furthermore, when expressed in Xenopus embryos, MTG family
      members inhibited axis formation and impaired the ability of beta-catenin and
      XLef-1 to induce axis duplication, indicating that MTG family members act
      downstream of beta-catenin. Moreover, we found that c-Myc, a transcriptional
      target of the Wnt pathway, was overexpressed in the small intestines of mice
      lacking Mtgr1, thus linking inactivation of Mtgr1 to the activation of a potent
      oncogene.

PMID- 18039849
TI  - Transcript-specific decapping and regulated stability by the human Dcp2 decapping
      protein.
AB  - mRNA decapping is a critical step in the control of mRNA stability and gene
      expression and is carried out by the Dcp2 decapping enzyme. Dcp2 is an RNA
      binding protein that must bind RNA in order to recognize the cap for hydrolysis.
      We demonstrate that human Dcp2 (hDcp2) preferentially binds to a subset of mRNAs
      and identify sequences at the 5' terminus of the mRNA encoding Rrp41, a core
      subunit component of the RNA exosome, as a specific hDcp2 substrate. A 60
      nucleotide element at the 5' end of Rrp41 mRNA was identified and shown to confer
      more efficient decapping on a heterologous RNA both in vitro and upon
      transfection into cells. Moreover, reduction of hDcp2 protein levels in cells
      resulted in a selective stabilization of the Rrp41 mRNA, confirming it as a
      downstream target of hDcp2 regulation. These findings demonstrate that hDcp2 can
      specifically bind to and regulate the stability of a subset of mRNAs, and its
      intriguing regulation of the 3'-to-5' exonuclease exosome subunit suggests a
      potential interplay between 5'-end mRNA decapping and 3'-end mRNA decay.

PMID- 18039850
TI  - Double-stranded RNA-binding protein regulates vascular endothelial growth factor
      mRNA stability, translation, and breast cancer angiogenesis.
AB  - Vascular endothelial growth factor (VEGF) is a key angiogenic factor expressed
      under restricted nutrient and oxygen conditions in most solid tumors. The
      expression of VEGF under hypoxic conditions requires transcription through
      activated hypoxia-inducible factor 1 (HIF-1), increased mRNA stability, and
      facilitated translation. This study identified double-stranded RNA-binding
      protein 76/NF90 (DRBP76/NF90), a specific isoform of the DRBP family, as a VEGF
      mRNA-binding protein which plays a key role in VEGF mRNA stability and protein
      synthesis under hypoxia. The DRBP76/NF90 protein binds to a human VEGF 3'
      untranslated mRNA stability element. RNA interference targeting the DRBP76/NF90
      isoform limited hypoxia-inducible VEGF mRNA and protein expression with no change
      in HIF-1-dependent transcriptional activity. Stable repression of DRBP76/NF90 in
      MDA-MB-435 breast cancer cells demonstrated reduced polysome-associated VEGF mRNA
      levels under hypoxic conditions and reduced mRNA stability. Transient
      overexpression of the DRBP76/NF90 protein increased both VEGF mRNA and protein
      levels synthesized under normoxic and hypoxic conditions. Cells with stable
      repression of the DRBP76/NF90 isoform showed reduced tumorigenic and angiogenic
      potential in an orthotopic breast tumor model. These data demonstrate that the
      DRBP76/NF90 isoform facilitates VEGF expression by promoting VEGF mRNA loading
      onto polysomes and translation under hypoxic conditions, thus promoting breast
      cancer growth and angiogenesis in vivo.

PMID- 18039851
TI  - Runx2 represses myocardin-mediated differentiation and facilitates osteogenic
      conversion of vascular smooth muscle cells.
AB  - Phenotypic plasticity and the switching of vascular smooth muscle cells (SMCs)
      play a critical role in atherosclerosis. Although Runx2, a key osteogenic
      transcription factor, is expressed in atherosclerotic plaques, the molecular
      mechanisms by which Runx2 regulates SMC differentiation remain unclear. Here we
      demonstrated that Runx2 repressed SMC differentiation induced by myocardin, which
      acts as a coactivator for serum response factor (SRF). Myocardin-mediated
      induction of SMC gene expression was enhanced in mouse embryonic fibroblasts
      derived from Runx2 null mice compared to wild-type mice. Forced expression of
      Runx2 decreased the expression of SMC genes and promoted osteogenic gene
      expression, whereas the reduction of Runx2 expression by small interfering RNA
      enhanced SMC differentiation in human aortic SMCs. Runx2 interacted with SRF and
      interfered with the formation of the SRF/myocardin ternary complex. Thus, this
      study provides the first evidence that Runx2 inhibits SRF-dependent
      transcription, as a corepressor independent of its DNA binding. We propose that
      Runx2 plays a pivotal role in osteogenic conversion tightly coupled with
      repression of the SMC phenotype in atherosclerotic lesions.

PMID- 18039852
TI  - PTB/hnRNP I is required for RNP remodeling during RNA localization in Xenopus
      oocytes.
AB  - Transport of specific mRNAs to defined regions within the cell cytoplasm is a
      fundamental mechanism for regulating cell and developmental polarity. In the
      Xenopus oocyte, Vg1 RNA is transported to the vegetal cytoplasm, where localized
      expression of the encoded protein is critical for embryonic polarity. The Vg1
      localization pathway is directed by interactions between key motifs within Vg1
      RNA and protein factors recognizing those RNA sequences. We have investigated how
      RNA-protein interactions could be modulated to trigger distinct steps in the
      localization pathway and found that the Vg1 RNP is remodeled during cytoplasmic
      RNA transport. Our results implicate two RNA-binding proteins with key roles in
      Vg1 RNA localization, PTB/hnRNP I and Vg1RBP/vera, in this process. We show that
      PTB/hnRNP I is required for remodeling of the interaction between Vg1 RNA and
      Vg1RBP/vera. Critically, mutations that block this remodeling event also
      eliminate vegetal localization of the RNA, suggesting that RNP remodeling is
      required for localization.

PMID- 18039853
TI  - Gcn5p plays an important role in centromere kinetochore function in budding
      yeast.
AB  - We report that the histone acetyltransferase Gcn5p is involved in cell cycle
      progression, whereas its absence induces several mitotic defects, including
      inefficient nuclear division, chromosome loss, delayed G(2) progression, and
      spindle elongation. The fidelity of chromosome segregation is finely regulated by
      the close interplay between the centromere and the kinetochore, a protein complex
      hierarchically assembled in the centromeric DNA region, while disruption of GCN5
      in mutants of inner components results in sick phenotype. These synthetic
      interactions involving the ADA complex lay the genetic basis for the critical
      role of Gcn5p in kinetochore assembly and function. We found that Gcn5p is, in
      fact, physically linked to the centromere, where it affects the structure of the
      variant centromeric nucleosome. Our findings offer a key insight into a Gcn5p
      dependent epigenetic regulation at centromere/kinetochore in mitosis.

PMID- 18039854
TI  - The MLE subunit of the Drosophila MSL complex uses its ATPase activity for dosage
      compensation and its helicase activity for targeting.
AB  - In Drosophila, dosage compensation-the equalization of most X-linked gene
      products between XY males and XX females-is mediated by the MSL complex that
      preferentially associates with numerous sites on the X chromosome in somatic
      cells of males, but not of females. The complex consists of a noncoding RNA and a
      core of five protein subunits that includes a histone acetyltransferase (MOF) and
      an ATP-dependent DEXH box RNA/DNA helicase (MLE). Both of these enzymatic
      activities are necessary for the spreading of the complex to its sites of action
      along the X chromosome. MLE is related to the ATPases present in complexes that
      remodel chromatin by altering the positioning or the architectural relationship
      between nucleosomes and DNA. In contrast to MLE, none of these enzymatic subunits
      has been shown to possess double-stranded nucleic acid-unwinding activity. We
      investigated the function of MLE in the process of dosage compensation by
      generating mutations that separate ATPase activity from duplex unwinding. We show
      that the ATPase activity is sufficient for MLE's role in transcriptional
      enhancement, while the helicase activity is necessary for the spreading of the
      complex along the X chromosome.

PMID- 18039855
TI  - Rad51-independent interchromosomal double-strand break repair by gene conversion
      requires Rad52 but not Rad55, Rad57, or Dmc1.
AB  - Homologous recombination (HR) is critical for DNA double-strand break (DSB)
      repair and genome stabilization. In yeast, HR is catalyzed by the Rad51 strand
      transferase and its "mediators," including the Rad52 single-strand DNA-annealing
      protein, two Rad51 paralogs (Rad55 and Rad57), and Rad54. A Rad51 homolog, Dmc1,
      is important for meiotic HR. In wild-type cells, most DSB repair results in gene
      conversion, a conservative HR outcome. Because Rad51 plays a central role in the
      homology search and strand invasion steps, DSBs either are not repaired or are
      repaired by nonconservative single-strand annealing or break-induced replication
      mechanisms in rad51Delta mutants. Although DSB repair by gene conversion in the
      absence of Rad51 has been reported for ectopic HR events (e.g., inverted repeats
      or between plasmids), Rad51 has been thought to be essential for DSB repair by
      conservative interchromosomal (allelic) gene conversion. Here, we demonstrate
      that DSBs stimulate gene conversion between homologous chromosomes (allelic
      conversion) by >30-fold in a rad51Delta mutant. We show that Rad51-independent
      allelic conversion and break-induced replication occur independently of Rad55,
      Rad57, and Dmc1 but require Rad52. Unlike DSB-induced events, spontaneous allelic
      conversion was detected in both rad51Delta and rad52Delta mutants, but not in a
      rad51Delta rad52Delta double mutant. The frequencies of crossovers associated
      with DSB-induced gene conversion were similar in the wild type and the rad51Delta
      mutant, but discontinuous conversion tracts were fivefold more frequent and tract
      lengths were more widely distributed in the rad51Delta mutant, indicating that
      heteroduplex DNA has an altered structure, or is processed differently, in the
      absence of Rad51.

PMID- 18039856
TI  - Differential chromatin looping regulates CD4 expression in immature thymocytes.
AB  - Runx1 binds the silencer and represses CD4 transcription in immature thymocytes.
      In this study, using looping chromatin immunoprecipitation and chromatin
      conformation capture assays, we demonstrated that interactions between Runx1 and
      positive elongation factor b (P-TEFb) appose the silencer and enhancer in CD4
      negative thymoma cells and double-negative immature thymocytes. This chromatin
      loop decoys P-TEFb away from the promoter, thus preventing RNA polymerase II from
      elongating on the CD4 gene. In the absence of Runx1 on the silencer, P-TEFb
      interacts with the transcription complex, forming a different chromatin loop
      between the enhancer and the promoter, which leads to the expression of the CD4
      gene in CD4-positive hybridoma cells and double-positive thymocytes. Moreover,
      the knockdown of CycT1 from P-TEFb abolishes both of these chromatin loops.
      Finally, the selective removal and restoration of Runx1 causes rapid interchanges
      between these chromatin loops, which reveals the plasticity of this regulatory
      circuit. Thus, differential looping and decoying of P-TEFb away from the promoter
      mediate active repression of the CD4 gene during thymocyte development.

PMID- 18039857
TI  - c-Src-mediated epithelial cell migration and invasion regulated by PDZ binding
      site.
AB  - c-Src tyrosine kinase controls proliferation, cell adhesion, and cell migration
      and is highly regulated. A novel regulatory mechanism to control c-Src function
      that has recently been identified involves the C-terminal amino acid sequence Gly
      Glu-Asn-Leu (GENL) of c-Src as ligand for PDZ domains. Herein, we determined the
      biological relevance of this c-Src regulation in human breast epithelial cells.
      The intact GENL sequence maintained c-Src in an inactive state in starved cells
      and restricted c-Src functions that might lead to metastatic transformation under
      normal growth conditions. c-Src with a C-terminal Leu/Ala mutation in GENL (Src
      A) promoted the activation and translocation of cortactin and focal adhesion
      kinase and increased the motility and persistence of cell migration on the
      basement membrane. Src-A promoted increased extracellular proteolytic activity,
      and in acinar cultures, it led to the escape of cells through the basement
      membrane into the surrounding matrix. We ascribe the regulatory function of C
      terminal Leu to the role of GENL in modulating c-Src activity downstream of cell
      matrix adhesion. We propose that the C terminus of c-Src via its GENL sequence
      presents a mechanism that restricts c-Src in epithelia and prevents progression
      toward an invasive phenotype.

PMID- 18039858
TI  - Expression levels of estrogen receptor beta are modulated by components of the
      molecular clock.
AB  - Circadian regulation of gene expression plays a major role in health and disease.
      The precise role of the circadian system remains to be clarified, but it is known
      that circadian proteins generate physiological rhythms in organisms by regulating
      clock-controlled target genes. The estrogen receptor beta (ERbeta) is, together
      with ERalpha, a member of the nuclear receptor superfamily and a key mediator of
      estrogen action. Interestingly, recent studies show that disturbed circadian
      rhythmicity in humans can increase the risk of reproductive malfunctions,
      suggesting a link between the circadian system and ER-mediated transcription
      pathways. Here, we identify a novel level of regulation of estrogen signaling
      where ERbeta, but not ERalpha, is controlled by circadian clock proteins. We show
      that ERbeta mRNA levels fluctuate in different peripheral tissues following a
      robust circadian pattern, with a peak at the light-dark transition, which is
      maintained under free-running conditions. Interestingly, this oscillation is
      abolished in clock-deficient BMAL1 knockout mice. Circadian control of ERbeta
      expression is exerted through a conserved E-box element in the ERbeta promoter
      region that recruits circadian regulatory factors. Furthermore, using small
      interfering RNA-mediated knockdown assays, we show that the expression levels of
      the circadian regulatory factors directly influence estrogen signaling by
      regulating the intracellular levels of endogenous ERbeta.

PMID- 18039859
TI  - Degradation of the tumor suppressor PML by Pin1 contributes to the cancer
      phenotype of breast cancer MDA-MB-231 cells.
AB  - Promyelocytic leukemia protein (PML) is an important regulator due to its role in
      numerous cellular processes including apoptosis, viral infection, senescence, DNA
      damage repair, and cell cycle regulation. Despite the role of PML in many
      cellular functions, little is known about the regulation of PML itself. We show
      that PML stability is regulated through interaction with the peptidyl-prolyl cis
      trans isomerase Pin1. This interaction is mediated through four serine-proline
      motifs in the C terminus of PML. Binding to Pin1 results in degradation of PML in
      a phosphorylation-dependent manner. Furthermore, our data indicate that
      sumoylation of PML blocks the interaction, thus preventing degradation of PML by
      this pathway. Functionally, we show that in the MDA-MB-231 breast cancer cell
      line modulating levels of Pin1 affects steady-state levels of PML. Furthermore,
      degradation of PML due to Pin1 acts both to protect these cells from hydrogen
      peroxide-induced death and to increase the rate of proliferation. Taken together,
      our work defines a novel mechanism by which sumoylation of PML prevents Pin1
      dependent degradation. This interaction likely occurs in numerous cell lines and
      may be a pathway for oncogenic transformation.

PMID- 18039860
TI  - MdmX promotes bipolar mitosis to suppress transformation and tumorigenesis in p53
      deficient cells and mice.
AB  - Mdm2 and MdmX are structurally related p53-binding proteins that function as
      critical negative regulators of p53 activity in embryonic and adult tissue. The
      overexpression of Mdm2 or MdmX inhibits p53 tumor suppressor functions in vitro,
      and the amplification of Mdm2 or MdmX is observed in human cancers retaining wild
      type p53. We now demonstrate a surprising role for MdmX in suppressing
      tumorigenesis that is distinct from its oncogenic ability to inhibit p53. The
      deletion of MdmX induces multipolar mitotic spindle formation and the loss of
      chromosomes from hyperploid p53-null cells. This reduction in chromosome number,
      not observed in p53-null cells with Mdm2 deleted, correlates with increased cell
      proliferation and the spontaneous transformation of MdmX/p53-null mouse embryonic
      fibroblasts in vitro and with an increased rate of spontaneous tumorigenesis in
      MdmX/p53-null mice in vivo. These results indicate that MdmX has a p53
      independent role in suppressing oncogenic cell transformation, proliferation, and
      tumorigenesis by promoting centrosome clustering and bipolar mitosis.

PMID- 18039861
TI  - Brd4 recruits P-TEFb to chromosomes at late mitosis to promote G1 gene expression
      and cell cycle progression.
AB  - Brd4, a bromodomain protein capable of interacting with acetylated histones, is
      implicated in transmitting epigenetic memory through mitosis. It also functions
      as an associated factor and positive regulator of P-TEFb, a Cdk9-cyclin T1
      heterodimer that stimulates transcriptional elongation by phosphorylating RNA
      polymerase II. In the present study, experiments were performed to determine
      whether these two functions of Brd4 are interrelated and, if so, how they may
      impact cell cycle progression. Our data demonstrate that while the P-TEFb level
      remains constant, the Brd4-P-TEFb interaction increases dramatically in cells
      progressing from late mitosis to early G(1). Concurrently, P-TEFb is recruited to
      chromosomes, beginning around mid- to late anaphase and before nuclear
      envelope/lamina formation and nuclear import of other general transcription
      factors. Importantly, the recruitment of P-TEFb depends on Brd4. Abrogation of
      this process through Brd4 knockdown reduces the binding of P-TEFb to and
      expression of key G(1) and growth-associated genes, leading to G(1) cell cycle
      arrest and apoptosis. Because P-TEFb is synonymous with productive elongation,
      its recruitment by Brd4 to chromosomes at late mitosis may indicate those genes
      whose active transcription status must be preserved across cell division.

PMID- 18039862
TI  - CTCF is the master organizer of domain-wide allele-specific chromatin at the
      H19/Igf2 imprinted region.
AB  - A paternally methylated imprinting control region (ICR) directs allele-specific
      expression of the imprinted H19 and Igf2 genes. CTCF protein binding in the ICR
      is required in the maternal chromosome for insulating Igf2 from the shared
      enhancers, initiation of the H19 promoter transcription, maintaining DNA
      hypomethylation, and chromosome loop formation. Using novel quantitative allele
      specific chromatin immunoprecipitation-single-nucleotide primer extension assays,
      we measured the chromatin composition along the H19/Igf2 imprinted domain in
      cells with engineered mutations at the four ICR-CTCF binding sites. Abolishing
      CTCF binding in the ICR reduced normally maternal allele-specific H3K9
      acetylation and H3K4 methylation at the H19 ICR and promoter/gene body and
      maternal allele-specific H3K27 trimethylation at the Igf2 P2 promoter and Igf2
      differentially methylated regions (DMRs). Paternal H3K27 trimethylation and
      macroH2A1 became biallelic in the mutant cells at the H19 promoter while paternal
      H3K9 acetylation and H3K4 methylation became biallelic at the Igf2 DMRs. We
      provide evidence that CTCF is the single major organizer of allele-specific
      chromatin composition in this domain. This finding has important implications:
      (i) for mechanisms of insulation since CTCF regulates chromatin at a distance,
      involving repression by H3K27 trimethylation at the Igf2 locus independently of
      repression by DNA hypermethylation; and (ii) for mechanisms of genomic imprinting
      since point mutations of CTCF binding sites cause domain-wide "paternalization"
      of the maternal allele's chromatin composition.

PMID- 18039863
TI  - Drosophila UTX is a histone H3 Lys27 demethylase that colocalizes with the
      elongating form of RNA polymerase II.
AB  - Histone H3 methylation at Lys27 (H3K27 methylation) is a hallmark of silent
      chromatin, while H3K4 methylation is associated with active chromatin regions.
      Here we report that a Drosophila JmjC family member, dUTX, specifically
      demethylates di- and trimethylated but not monomethylated H3K27. dUTX
      localization on chromatin correlates with the elongating form of RNA polymerase
      II (Pol II), and dUTX can associate with Pol II. Furthermore, heat shock
      induction results in the recruitment of dUTX to the hsp70 gene, like that of
      several other Pol II elongation factors. Our data indicate that dUTX is
      intimately associated with actively transcribed genes and may provide a paradigm
      for how H3K27 demethylation is required for the activation of preinitiated Pol II
      on transcriptionally poised genes.

PMID- 18039865
TI  - Drosophila Genomes by the Baker's Dozen. Preface.

PMID- 18039866
TI  - Drosophila biology in the genomic age.
AB  - Over the course of the past century, flies in the family Drosophilidae have been
      important models for understanding genetic, developmental, cellular, ecological,
      and evolutionary processes. Full genome sequences from a total of 12 species
      promise to extend this work by facilitating comparative studies of gene
      expression, of molecules such as proteins, of developmental mechanisms, and of
      ecological adaptation. Here we review basic biological and ecological information
      of the species whose genomes have recently been completely sequenced in the
      context of current research.

PMID- 18039867
TI  - Analysis of Drosophila species genome size and satellite DNA content reveals
      significant differences among strains as well as between species.
AB  - The size of eukaryotic genomes can vary by several orders of magnitude, yet
      genome size does not correlate with the number of genes nor with the size or
      complexity of the organism. Although "whole"-genome sequences, such as those now
      available for 12 Drosophila species, provide information about euchromatic DNA
      content, they cannot give an accurate estimate of genome sizes that include
      heterochromatin or repetitive DNA content. Moreover, genome sequences typically
      represent only one strain or isolate of a single species that does not reflect
      intraspecies variation. To more accurately estimate whole-genome DNA content and
      compare these estimates to newly assembled genomes, we used flow cytometry to
      measure the 2C genome values, relative to Drosophila melanogaster. We estimated
      genome sizes for the 12 sequenced Drosophila species as well as 91 different
      strains of 38 species of Drosophilidae. Significant differences in intra- and
      interspecific 2C genome values exist within the Drosophilidae. Furthermore, by
      measuring polyploid 16C ovarian follicle cell underreplication we estimated the
      amount of satellite DNA in each of these species. We found a strong correlation
      between genome size and amount of satellite underreplication. Addition and loss
      of heterochromatin satellite repeat elements appear to have made major
      contributions to the large differences in genome size observed in the
      Drosophilidae.

PMID- 18039868
TI  - Conservation of epigenetic regulation, ORC binding and developmental timing of
      DNA replication origins in the genus Drosophila.
AB  - There is much interest in how DNA replication origins are regulated so that the
      genome is completely duplicated each cell division cycle and in how the division
      of cells is spatially and temporally integrated with development. In the
      Drosophila melanogaster ovary, the cell cycle of somatic follicle cells is
      modified at precise times in oogenesis. Follicle cells first proliferate via a
      canonical mitotic division cycle and then enter an endocycle, resulting in their
      polyploidization. They subsequently enter a specialized amplification phase
      during which only a few, select origins repeatedly initiate DNA replication,
      resulting in gene copy number increases at several loci important for eggshell
      synthesis. Here we investigate the importance of these modified cell cycles for
      oogenesis by determining whether they have been conserved in evolution. We find
      that their developmental timing has been strictly conserved among Drosophila
      species that have been separate for approximately 40 million years of evolution
      and provide evidence that additional gene loci may be amplified in some species.
      Further, we find that the acetylation of nucleosomes and Orc2 protein binding at
      active amplification origins is conserved. Conservation of DNA subsequences
      within amplification origins from the 12 recently sequenced Drosophila species
      genomes implicates members of a Myb protein complex in recruiting acetylases to
      the origin. Our findings suggest that conserved developmental mechanisms
      integrate egg chamber morphogenesis with cell cycle modifications and the
      epigenetic regulation of origins.

PMID- 18039870
TI  - Variable strength of translational selection among 12 Drosophila species.
AB  - Codon usage bias in Drosophila melanogaster genes has been attributed to negative
      selection of those codons whose cellular tRNA abundance restricts rates of mRNA
      translation. Previous studies, which involved limited numbers of genes, can now
      be compared against analyses of the entire gene complements of 12 Drosophila
      species whose genome sequences have become available. Using large numbers (6138)
      of orthologs represented in all 12 species, we establish that the codon
      preferences of more closely related species are better correlated. Differences
      between codon usage biases are attributed, in part, to changes in mutational
      biases. These biases are apparent from the strong correlation (r = 0.92, P <
      0.001) among these genomes' intronic G + C contents and exonic G + C contents at
      degenerate third codon positions. To perform a cross-species comparison of
      selection on codon usage, while accounting for changes in mutational biases, we
      calibrated each genome in turn using the codon usage bias indices of highly
      expressed ribosomal protein genes. The strength of translational selection was
      predicted to have varied between species largely according to their phylogeny,
      with the D. melanogaster group species exhibiting the strongest degree of
      selection.

PMID- 18039869
TI  - Evolution in the fast lane: rapidly evolving sex-related genes in Drosophila.
AB  - A large portion of the annotated genes in Drosophila melanogaster show sex-biased
      expression, indicating that sex and reproduction-related genes (SRR genes)
      represent an appreciable component of the genome. Previous studies, in which
      subsets of genes were compared among few Drosophila species, have found that SRR
      genes exhibit unusual evolutionary patterns. Here, we have used the newly
      released genome sequences from 12 Drosophila species, coupled to a larger set of
      SRR genes, to comprehensively test the generality of these patterns. Among 2505
      SRR genes examined, including ESTs with biased expression in reproductive tissues
      and genes characterized as involved in gametogenesis, we find that a relatively
      high proportion of SRR genes have experienced accelerated divergence throughout
      the genus Drosophila. Several testis-specific genes, male seminal fluid proteins
      (SFPs), and spermatogenesis genes show lineage-specific bursts of accelerated
      evolution and positive selection. SFP genes also show evidence of lineage
      specific gene loss and/or gain. These results bring us closer to understanding
      the details of the evolutionary dynamics of SRR genes with respect to species
      divergence.

PMID- 18039871
TI  - Phylogenetic and genomewide analyses suggest a functional relationship between
      kayak, the Drosophila fos homolog, and fig, a predicted protein phosphatase 2c
      nested within a kayak intron.
AB  - A gene located within the intron of a larger gene is an uncommon arrangement in
      any species. Few of these nested gene arrangements have been explored from an
      evolutionary perspective. Here we report a phylogenetic analysis of kayak (kay)
      and fos intron gene (fig), a divergently transcribed gene located in a kay
      intron, utilizing 12 Drosophila species. The evolutionary relationship between
      these genes is of interest because kay is the homolog of the proto-oncogene c-fos
      whose function is modulated by serine/threonine phosphorylation and fig is a
      predicted PP2C phosphatase specific for serine/threonine residues. We found that,
      despite an extraordinary level of diversification in the intron-exon structure of
      kay (11 inversions and six independent exon losses), the nested arrangement of
      kay and fig is conserved in all species. A genomewide analysis of protein-coding
      nested gene pairs revealed that approximately 20% of nested pairs in D.
      melanogaster are also nested in D. pseudoobscura and D. virilis. A phylogenetic
      examination of fig revealed that there are three subfamilies of PP2C phosphatases
      in all 12 species of Drosophila. Overall, our phylogenetic and genomewide
      analyses suggest that the nested arrangement of kay and fig may be due to a
      functional relationship between them.

PMID- 18039872
TI  - Molecular evolution of glutathione S-transferases in the genus Drosophila.
AB  - As classical phase II detoxification enzymes, glutathione S-transferases (GSTs)
      have been implicated in insecticide resistance and may have evolved in response
      to toxins in the niche-defining feeding substrates of Drosophila species. We have
      annotated the GST genes of the 12 Drosophila species with recently sequenced
      genomes and analyzed their molecular evolution. Gene copy number variation is
      attributable mainly to unequal crossing-over events in the large delta and
      epsilon clusters. Within these gene clusters there are also GST genes with slowly
      diverging orthologs. This implies that they have their own unique functions or
      have spatial/temporal expression patterns that impose significant selective
      constraints. Searches for positively selected sites within the GSTs identified
      G171K in GSTD1, a protein that has previously been shown to be capable of
      metabolizing the insecticide DDT. We find that the same radical substitution
      (G171K) in the substrate-binding domain has occurred at least three times in the
      Drosophila radiation. Homology-modeling places site 171 distant from the active
      site but adjacent to an alternative DDT-binding site. We propose that the
      parallel evolution observed at this site is an adaptive response to an
      environmental toxin and that sequencing of historical alleles suggests that this
      toxin was not a synthetic insecticide.

PMID- 18039874
TI  - Five Drosophila genomes reveal nonneutral evolution and the signature of host
      specialization in the chemoreceptor superfamily.
AB  - The insect chemoreceptor superfamily comprises the olfactory receptor (Or) and
      gustatory receptor (Gr) multigene families. These families give insects the
      ability to smell and taste chemicals in the environment and are thus rich
      resources for linking molecular evolutionary and ecological processes. Although
      dramatic differences in family size among distant species and high divergence
      among paralogs have led to the belief that the two families evolve rapidly, a
      lack of evolutionary data over short time scales has frustrated efforts to
      identify the major forces shaping this evolution. Here, we investigate patterns
      of gene loss/gain, divergence, and polymorphism in the entire repertoire of
      approximately 130 chemoreceptor genes from five closely related species of
      Drosophila that share a common ancestor within the past 12 million years. We
      demonstrate that the overall evolution of the Or and Gr families is nonneutral.
      We also show that selection regimes differ both between the two families as
      wholes and within each family among groups of genes with varying functions,
      patterns of expression, and phylogenetic histories. Finally, we find that the
      independent evolution of host specialization in Drosophila sechellia and D.
      erecta is associated with a fivefold acceleration of gene loss and increased
      rates of amino acid evolution at receptors that remain intact. Gene loss appears
      to primarily affect Grs that respond to bitter compounds while elevated Ka/Ks is
      most pronounced in the subset of Ors that are expressed in larvae. Our results
      provide strong evidence that the observed phenomena result from the invasion of a
      novel ecological niche and present a unique synthesis of molecular evolutionary
      analyses with ecological data.

PMID- 18039873
TI  - Phylogenetic footprinting analysis in the upstream regulatory regions of the
      Drosophila enhancer of split genes.
AB  - During Drosophila development Suppressor of Hairless [Su(H)]-dependent Notch
      activation upregulates transcription of the Enhancer of split-Complex [E(spl)-C]
      genes. Drosophila melanogaster E(spl) genes share common transcription regulators
      including binding sites for Su(H), proneural, and E(spl) basic-helix-loop-helix
      (bHLH) proteins. However, the expression patterns of E(spl) genes during
      development suggest that additional factors are involved. To better understand
      regulators responsible for these expression patterns, recently available sequence
      and annotation data for multiple Drosophila genomes were used to compare the
      E(spl) upstream regulatory regions from more than nine Drosophila species. The
      mgamma and mbeta regulatory regions are the most conserved of the bHLH genes.
      Fine analysis of Su(H) sites showed that high-affinity Su(H) paired sites and the
      Su(H) paired site plus proneural site (SPS + A) architecture are completely
      conserved in a subset of Drosophila E(spl) genes. The SPS + A module is also
      present in the upstream regulatory regions of the more ancient mosquito and
      honeybee E(spl) bHLH genes. Additional transcription factor binding sites were
      identified upstream of the E(spl) genes and compared between species of
      Drosophila. Conserved sites provide new understandings about E(spl) regulation
      during development. Conserved novel sequences found upstream of multiple E(spl)
      genes may play a role in the expression of these genes.

PMID- 18039875
TI  - Divergence between the Drosophila pseudoobscura and D. persimilis genome
      sequences in relation to chromosomal inversions.
AB  - As whole-genome sequence assemblies accumulate, a challenge is to determine how
      these can be used to address fundamental evolutionary questions, such as
      inferring the process of speciation. Here, we use the sequence assemblies of
      Drosophila pseudoobscura and D. persimilis to test hypotheses regarding
      divergence with gene flow. We observe low differentiation between the two genome
      sequences in pericentromeric and peritelomeric regions. We interpret this result
      as primarily a remnant of the correlation between levels of variation and local
      recombination rate observed within populations. However, we also observe lower
      differentiation far from the fixed chromosomal inversions distinguishing these
      species and greater differentiation within and near these inversions. This
      finding is consistent with models suggesting that chromosomal inversions
      facilitate species divergence despite interspecies gene flow. We also document
      heterogeneity among the inverted regions in their degree of differentiation,
      suggesting temporal differences in the origin of each inverted region consistent
      with the inversions arising during a process of divergence with gene flow. While
      this study provides insights into the speciation process using two single-genome
      sequences, it was informed by lower throughput but more rigorous examinations of
      polymorphism and divergence. This reliance highlights the need for complementary
      genomic and population genetic approaches for tackling fundamental evolutionary
      questions such as speciation.

PMID- 18039876
TI  - An evolutionarily conserved domain of roX2 RNA is sufficient for induction of H4
      Lys16 acetylation on the Drosophila X chromosome.
AB  - The male-specific lethal (MSL) complex, which includes two noncoding RNA on X
      (roX)1 and roX2 RNAs, induces histone H4-Lys16 acetylation for twofold
      hypertranscription of the male X chromosome in Drosophila melanogaster. To
      characterize the role of roX RNAs in this process, we have identified
      evolutionarily conserved functional domains of roX RNAs in several Drosophila
      species (eight for roX1 and nine for roX2). Despite low homology between them,
      male-specific expression and X chromosome-specific binding are conserved. Within
      roX RNAs of all Drosophila species, we found conserved primary sequences, such as
      GUUNUACG, in the 3' end of both roX1 (three repeats) and roX2 (two repeats). A
      predicted stem-loop structure of roX2 RNA contains this sequence in the 3' stem
      region. Six tandem repeats of this stem-loop region (72 nt) of roX2 were enough
      for targeting the MSL complex and inducing H4-Lys16 acetylation on the X
      chromosome without other parts of roX2 RNA, suggesting that roX RNAs might play
      important roles in regulating enzymatic activity of the MSL complex.

PMID- 18039877
TI  - Guido Pontecorvo ("Ponte"): a centenary memoir.

PMID- 18039878
TI  - The role of Sse1 in the de novo formation and variant determination of the [PSI+]
      prion.
AB  - Yeast prions are a group of non-Mendelian genetic elements transmitted as altered
      and self-propagating conformations. Extensive studies in the last decade have
      provided valuable information on the mechanisms responsible for yeast prion
      propagation. How yeast prions are formed de novo and what cellular factors are
      required for determining prion "strains" or variants--a single polypeptide
      capable of existing in multiple conformations to result in distinct heritable
      phenotypes--continue to defy our understanding. We report here that Sse1, the
      yeast ortholog of the mammalian heat-shock protein 110 (Hsp110) and a nucleotide
      exchange factor for Hsp70 proteins, plays an important role in regulating [PSI+]
      de novo formation and variant determination. Overproduction of the Sse1 chaperone
      dramatically enhanced [PSI+] formation whereas deletion of SSE1 severely
      inhibited it. Only an unstable weak [PSI+] variant was formed in SSE1 disrupted
      cells whereas [PSI+] variants ranging from very strong to very weak were formed
      in isogenic wild-type cells under identical conditions. Thus, Sse1 is essential
      for the generation of multiple [PSI+] variants. Mutational analysis further
      demonstrated that the physical association of Sse1 with Hsp70 but not the ATP
      hydrolysis activity of Sse1 is required for the formation of multiple [PSI+]
      variants. Our findings establish a novel role for Sse1 in [PSI+] de novo
      formation and variant determination, implying that the mammalian Hsp110 may
      likewise be involved in the etiology of protein-folding diseases.

PMID- 18039879
TI  - A mutant dec-1 transgene induces dominant female sterility in Drosophila
      melanogaster.
AB  - The Drosophila dec-1 gene produces three proproteins required for female
      fertility and eggshell assembly. The three proproteins are distinguished by their
      C termini. Fc106, the most abundant proprotein, is cleaved within the vitelline
      membrane to three mature derivatives in a developmentally regulated manner. To
      define sequences within fc106 that are critical for its function, we created wild
      type and mutant versions of an fc106 cDNA transgene. The functional consequences
      of the mutations were assessed in dec-14, a female-sterile splicing mutant that
      does not produce the fc106 isoform. The fertility of dec-14 females was restored
      by the introduction of either a wild-type transgene or a transgene bearing a C
      terminal deletion that included fc106-specific sequences. Surprisingly, the
      removal of internal coding sequences created an aberrant DEC-1 proprotein that
      induced female sterility when introduced into wild-type flies. Dominant female
      sterility was not associated with larger deletions that included the fc106 N
      terminus, suggesting that abnormal juxtaposition of N- and C-terminal sequences
      in the aberrant proprotein interfered with endogenous DEC-1 proteins. Changes in
      the fractionation behavior of the endogenous fc106 C-terminal derivative, s60,
      and morphological changes in the endochorion in response to expression of the
      aberrant proprotein support this interpretation.

PMID- 18039880
TI  - Expression of the Drosophila melanogaster GADD45 homolog (CG11086) affects egg
      asymmetric development that is mediated by the c-Jun N-terminal kinase pathway.
AB  - The mammalian GADD45 (growth arrest and DNA-damage inducible) gene family is
      composed of three highly homologous small, acidic, nuclear proteins: GADD45alpha,
      GADD45beta, and GADD45gamma. GADD45 proteins are involved in important processes
      such as regulation of DNA repair, cell cycle control, and apoptosis. Annotation
      of the Drosophila melanogaster genome revealed that it contains a single GADD45
      like protein (CG11086; D-GADD45). We found that, as its mammalian homologs, D
      GADD45 is a nuclear protein; however, D-GADD45 expression is not elevated
      following exposure to genotoxic and nongenotoxic agents in Schneider cells and in
      adult flies. We showed that the D-GADD45 transcript increased following immune
      response activation, consistent with previous microarray findings. Since
      upregulation of GADD45 proteins has been characterized as an important cellular
      response to genotoxic and nongenotoxic agents, we aimed to characterize the
      effect of D-GADD45 overexpression on D. melanogaster development. Overexpression
      of D-GADD45 in various tissues led to different phenotypic responses.
      Specifically, in the somatic follicle cells overexpression caused apoptosis,
      while overexpression in the germline affected the dorsal-ventral polarity of the
      eggshell and disrupted the localization of anterior-posterior polarity
      determinants. In this article we focused on the role of D-GADD45 overexpression
      in the germline and found that D-GADD45 caused dorsalization of the eggshell.
      Since mammalian GADD45 proteins are activators of the c-Jun N-terminal kinase
      (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling pathways, we tested
      for a genetic interaction in D. melanogaster. We found that eggshell polarity
      defects caused by D-GADD45 overexpression were dominantly suppressed by mutations
      in the JNK pathway, suggesting that the JNK pathway has a novel, D-GADD45
      mediated, function in the Drosophila germline.

PMID- 18039882
TI  - Extensive concerted evolution of rice paralogs and the road to regaining
      independence.
AB  - Many genes duplicated by whole-genome duplications (WGDs) are more similar to one
      another than expected. We investigated whether concerted evolution through
      conversion and crossing over, well-known to affect tandem gene clusters, also
      affects dispersed paralogs. Genome sequences for two Oryza subspecies reveal
      appreciable gene conversion in the approximately 0.4 MY since their divergence,
      with a gradual progression toward independent evolution of older paralogs. Since
      divergence from subspecies indica, approximately 8% of japonica paralogs produced
      5-7 MYA on chromosomes 11 and 12 have been affected by gene conversion and
      several reciprocal exchanges of chromosomal segments, while approximately 70-MY
      old "paleologs" resulting from a genome duplication (GD) show much less
      conversion. Sequence similarity analysis in proximal gene clusters also suggests
      more conversion between younger paralogs. About 8% of paleologs may have been
      converted since rice-sorghum divergence approximately 41 MYA. Domain-encoding
      sequences are more frequently converted than nondomain sequences, suggesting a
      sort of circularity--that sequences conserved by selection may be further
      conserved by relatively frequent conversion. The higher level of concerted
      evolution in the 5-7 MY-old segmental duplication may reflect the behavior of
      many genomes within the first few million years after duplication or
      polyploidization.

PMID- 18039883
TI  - The role of epistasis in the manifestation of heterosis: a systems-oriented
      approach.
AB  - Heterosis is widely used in breeding, but the genetic basis of this biological
      phenomenon has not been elucidated. We postulate that additive and dominance
      genetic effects as well as two-locus interactions estimated in classical QTL
      analyses are not sufficient for quantifying the contributions of QTL to
      heterosis. A general theoretical framework for determining the contributions of
      different types of genetic effects to heterosis was developed. Additive x
      additive epistatic interactions of individual loci with the entire genetic
      background were identified as a major component of midparent heterosis. On the
      basis of these findings we defined a new type of heterotic effect denoted as
      augmented dominance effect di* that comprises the dominance effect at each QTL
      minus half the sum of additive x additive interactions with all other QTL. We
      demonstrate that genotypic expectations of QTL effects obtained from analyses
      with the design III using testcrosses of recombinant inbred lines and composite
      interval mapping precisely equal genotypic expectations of midparent heterosis,
      thus identifying genomic regions relevant for expression of heterosis. The theory
      for QTL mapping of multiple traits is extended to the simultaneous mapping of
      newly defined genetic effects to improve the power of QTL detection and
      distinguish between dominance and overdominance.

PMID- 18039881
TI  - Demographic history has influenced nucleotide diversity in European Pinus
      sylvestris populations.
AB  - To infer the role of natural selection in shaping standing genetic diversity, it
      is necessary to assess the genomewide impact of demographic history on nucleotide
      diversity. In this study we analyzed sequence diversity of 16 nuclear loci in
      eight Pinus sylvestris populations. Populations were divided into four
      geographical groups on the basis of their current location and the geographical
      history of the region: northern Europe, central Europe, Spain, and Turkey. There
      were no among-group differences in the level of silent nucleotide diversity,
      which was approximately 0.005/bp in all groups. There was some evidence that
      linkage disequilibrium extended further in northern Europe than in central
      Europe: the estimates of the population recombination rate parameter, rho, were
      0.0064 and 0.0294, respectively. The summary statistics of nucleotide diversity
      in central and northern European populations were compatible with an ancient
      bottleneck rather than the standard neutral model.

PMID- 18039884
TI  - Genetic basis of heterosis for growth-related traits in Arabidopsis investigated
      by testcross progenies of near-isogenic lines reveals a significant role of
      epistasis.
AB  - Epistasis seems to play a significant role in the manifestation of heterosis.
      However, the power of detecting epistatic interactions among quantitative trait
      loci (QTL) in segregating populations is low. We studied heterosis in Arabidopsis
      thaliana hybrid C24 x Col-0 by testing near-isogenic lines (NILs) and their
      triple testcross (TTC) progenies. Our objectives were to (i) provide the
      theoretical basis for estimating different types of genetic effects with this
      experimental design, (ii) determine the extent of heterosis for seven growth
      related traits, (iii) map the underlying QTL, and (iv) determine their gene
      action. Two substitution libraries, each consisting of 28 NILs and covering
      approximately 61 and 39% of the Arabidopsis genome, were assayed by 110 single
      nucleotide polymorphism (SNP) markers. With our novel generation means approach
      38 QTL were detected, many of which confirmed heterotic QTL detected previously
      in the same cross with TTC progenies of recombinant inbred lines. Furthermore,
      many of the QTL were common for different traits and in common with the 58 QTL
      detected by a method that compares triplets consisting of a NIL, its recurrent
      parent, and their F(1) cross. While the latter approach revealed mostly (75%)
      overdominant QTL, the former approach allowed separation of dominance and
      epistasis by analyzing all materials simultaneously and yielded substantial
      positive additive x additive effects besides directional dominance. Positive
      epistatic effects reduced heterosis for growth-related traits in our materials.

PMID- 18039885
TI  - Heterosis for biomass-related traits in Arabidopsis investigated by quantitative
      trait loci analysis of the triple testcross design with recombinant inbred lines.
AB  - Arabidopsis thaliana has emerged as a leading model species in plant genetics and
      functional genomics including research on the genetic causes of heterosis. We
      applied a triple testcross (TTC) design and a novel biometrical approach to
      identify and characterize quantitative trait loci (QTL) for heterosis of five
      biomass-related traits by (i) estimating the number, genomic positions, and
      genetic effects of heterotic QTL, (ii) characterizing their mode of gene action,
      and (iii) testing for presence of epistatic effects by a genomewide scan and
      marker x marker interactions. In total, 234 recombinant inbred lines (RILs) of
      Arabidopsis hybrid C24 x Col-0 were crossed to both parental lines and their F1
      and analyzed with 110 single-nucleotide polymorphism (SNP) markers. QTL analyses
      were conducted using linear transformations Z1, Z2, and Z3 calculated from the
      adjusted entry means of TTC progenies. With Z1, we detected 12 QTL displaying
      augmented additive effects. With Z2, we mapped six QTL for augmented dominance
      effects. A one-dimensional genome scan with Z3 revealed two genomic regions with
      significantly negative dominance x additive epistatic effects. Two-way analyses
      of variance between marker pairs revealed nine digenic epistatic interactions:
      six reflecting dominance x dominance effects with variable sign and three
      reflecting additive x additive effects with positive sign. We conclude that
      heterosis for biomass-related traits in Arabidopsis has a polygenic basis with
      overdominance and/or epistasis being presumably the main types of gene action.

PMID- 18039886
TI  - Computing heritability and selection response from unbalanced plant breeding
      trials.
AB  - Heritability is often used by plant breeders and geneticists as a measure of
      precision of a trial or a series of trials. Its main use is for computing the
      response to selection. Most formulas proposed for calculating heritability
      implicitly assume balanced data and independent genotypic effects. Both of these
      assumptions are often violated in plant breeding trials. This article proposes a
      simulation-based approach to tackle the problem. The key idea is to directly
      simulate the quantity of interest, e.g., response to selection, rather than
      trying to approximate it using some ad hoc measure of heritability. The approach
      is illustrated by three examples.

PMID- 18039887
TI  - Drosophila G9a is a nonessential gene.
AB  - Mammalian G9a is a euchromatic histone H3 lysine 9 (H3K9) methyltransferase
      essential for development. Here, we characterize the Drosophila homolog of G9a,
      dG9a. We generated a dG9a deletion allele by homologous recombination. Analysis
      of this allele revealed that, in contrast to recent findings, dG9a is not
      required for fly viability.

PMID- 18039888
TI  - Pervasive and largely lineage-specific adaptive protein evolution in the dosage
      compensation complex of Drosophila melanogaster.
AB  - Dosage compensation refers to the equalization of X-linked gene transcription
      among heterogametic and homogametic sexes. In Drosophila, the dosage compensation
      complex (DCC) mediates the twofold hypertranscription of the single male X
      chromosome. Loss-of-function mutations at any DCC protein-coding gene are male
      lethal. Here we report a population genetic analysis suggesting that four of the
      five core DCC proteins--MSL1, MSL2, MSL3, and MOF--are evolving under positive
      selection in D. melanogaster. Within these four proteins, several domains that
      range in function from X chromosome localization to protein-protein interactions
      have elevated, D. melanogaster-specific, amino acid divergence.

PMID- 18039889
TI  - Compensatory strategies for acquired disorders of memory and planning:
      differential effects of a paging system for patients with brain injury of
      traumatic versus cerebrovascular aetiology.
AB  - BACKGROUND: Previous studies have demonstrated the effectiveness of paging
      systems in compensating for everyday memory and planning problems after brain
      injury, including in individuals with traumatic brain injury (TBI). METHODS:
      Here, in addition to further analyses of the TBI data from a previous randomised
      control crossover trial, results are reported from a sub-group of 36 participants
      with brain injury from cerebrovascular accident (CVA). RESULTS: Results indicate
      that, as with the TBI group, the pager was effective. However, the pattern of
      results following cessation of treatment differed. At a group level, TBI
      participants demonstrated maintenance of pager-related benefits, whereas CVA
      participants' performance returned to baseline levels. Comparisons of demographic
      and neuropsychological characteristics of the groups showed that the CVA group
      was older, had a shorter interval post-injury, and had poorer executive function
      than the TBI group. Furthermore, within the TBI group, maintenance was associated
      with executive functioning, such that executive dysfunction impeded maintenance.
      This correlation remained after controlling for demographic differences between
      groups. CONCLUSIONS: Together, these findings suggest that executive dysfunction
      may affect treatment-for example, whether or not temporary use of the pager is
      sufficient to establish a subsequently self-sustaining routine.

PMID- 18039890
TI  - Disappearance of "phantom limb" and amputated arm usage during dreaming in REM
      sleep behaviour disorder.

PMID- 18039891
TI  - Anticipatory postural adjustments associated with arm movement in Parkinson's
      disease: a biomechanical analysis.
AB  - OBJECTIVE: To study anticipatory postural adjustments (APAs) in Parkinson's
      disease (PD) via a biomechanical analysis, including vertical torque (Tz).
      METHODS: Ten patients with PD (in the "off-drug" condition) and 10 age matched
      controls were included. While standing on a force platform, the subject performed
      a right shoulder flexion in order to grasp a handle in front of him/her, under
      three conditions (all at maximal velocity): movement triggered by a sound signal
      and loaded/non-loaded, self-paced movement. The anteroposterior coordinates of
      the centre of pressure (COP) and Tz were calculated. RESULTS: A group effect was
      observed for Tz and COP in patients with PD (compared with controls): the maximal
      velocity peak appeared later and the amplitude of the COP backward displacement
      and the area of the positive phase of Tz were lower, whereas the duration of the
      positive phase of Tz was greater. Interaction analysis showed that the area of Tz
      was especially affected in the triggered condition and the loaded, self-paced
      condition. The onset of the COP backward displacement was delayed in the
      triggered condition. CONCLUSION: Our biomechanical analysis revealed that
      patients with PD do indeed perform APAs prior to unilateral arm movement,
      although there were some abnormalities. The reduced APA magnitude appears to
      correspond to a strategy for not endangering postural balance.

PMID- 18039892
TI  - Eosinophilic substance is "not amyloid" in the mouse nasal septum.
AB  - An eosinophilic substance (ES) is usually observed in the mouse nasal septum and
      increases in volume with aging. It has been described as amyloid in textbooks and
      one report. However, it has been described as "not amyloid" in other reports
      because there was a negative reaction to Congo red. In this study, the ES was
      investigated histopathologically and electron microscopically to determine
      whether it was amyloid or not. The ES was only observed at the interstitium of
      clear HE-stained nasal glands in the septum, in which 2 kinds of glands were
      present (dark and clear stained by HE). The volume of the ES was small in young
      mice and large in older ones. Neither nasal gland degeneration nor inflammation
      resulted, even if a large amount of the ES was observed. The ES reacted
      negatively to Congo red but was strongly positive to periodic acid-Schiff
      reaction with prior diastase treatment. In the electron microscope observation,
      the ES consisted of amorphous material and collagen, but no nonbranching fibrils.
      Similar amorphous material was also observed in the nasal gland epithelial cells
      and was connected to the material in the rough endoplasmic reticulum. The above
      mentioned findings indicated that the ES was not amyloid and suggested the ES
      might consist of not only collagen but also complex carbohydrate, which was
      produced by the nasal gland epithelial cells.

PMID- 18039894
TI  - The distribution and density of Clostridium difficile toxin receptors on the
      intestinal mucosa of neonatal pigs.
AB  - Clostridium difficile is an enteric pathogen affecting a variety of mammals, but
      it has only recently been diagnosed as a cause of neonatal typhlocolitis in pigs.
      The most important virulence factors of C. difficile are 2 large exotoxins, toxin
      A (TcdA) and toxin B (TcdB). TcdA is a potent enterotoxin with effects on host
      tissues that are dependent upon receptor-mediated endocytosis of the intact
      toxin. TcdB is an effective cytotoxin, but it apparently does not bind receptors
      on intact mucosal epithelium. TcdB is much less toxic in vivo unless there is
      underlying damage to the mucosa, and it is not essential for the virulence of C.
      difficile. One hypothesis to explain the resistance of most species as neonates
      (e.g., humans and hamsters) is that they may lack significant numbers of TcdA
      receptors. The susceptibility of neonatal pigs suggests cells of the
      gastrointestinal mucosa express sufficient numbers of toxin receptors for lesion
      development. Immunohistochemical (IHC) assays documented specific binding of
      TcdA, but not TcdB, to the epithelium of the small and large intestine. The
      carbohydrate Galalpha1-3beta1-4GlcNAc-R has been described as an important
      receptor for TcdA. However, IHC indicated a distribution on cell surfaces much
      different from that of TcdA binding, suggesting a specific interaction of toxin
      with an alternative receptor.

PMID- 18039893
TI  - Tenascin-C in chronic canine hepatitis: immunohistochemical localization and
      correlation with necro-inflammatory activity, fibrotic stage, and expression of
      alpha-smooth muscle actin, cytokeratin 7, and CD3+ cells.
AB  - During fibrosis, the extracellular matrix (ECM) is continuously remodeled and
      increases in volume due to the production of various proteins. We studied the
      distribution of tenascin-C (TN-C) and the correlation of TN-C with the necro
      inflammatory activity and expression of alpha-smooth muscle actin (alpha-SMA),
      cytokeratin 7 (CK7), and CD3+ T-lymphocytes in canine chronic hepatitis. This was
      analyzed using immunohistochemistry and semiquantitative scoring. We used 3
      groups (n = 19) of dogs: group 1 (n = 5) with neonatal hepatitis/lobular
      dissecting hepatitis (NH/LDH), group 2 (n = 8) with chronic hepatitis/cirrhosis
      (CH/CIRR), and group 3 (n = 6) consisting of healthy animals. In normal livers,
      TN-C was localized in Disse's space and around bile ducts and blood vessels. In
      CH/CIRR livers, TN-C was localized at the periphery of the regenerating nodules
      and was conspicuous in the bridging fibrous bands. In NH/LDH, TN-C was diffusely
      distributed along the reticular fibers that dissected between single cells or
      groups of hepatocytes. alpha-SMA in the normal hepatic parenchyma showed an
      irregular distribution along the perisinusoidal linings. In other groups, alpha
      SMA was increased in fibrotic septa and perisinusoidal linings. In normal livers,
      CK7 was positive in bile ducts. In other groups, CK7-expressing cells were
      conspicuous in the portal-parenchymal interface, the periphery of the
      regenerative nodules, and the degenerated parenchyma. The pattern of CD3+
      lymphocytes was inversely proportional to that of TN-C. These results also showed
      that TN-C is strongly correlated with increased fibrotic stage, inflammatory
      activity, and expression of CK7 and alpha-SMA. TN-C, CK7, and CD3 expression did
      not differ between diagnostic groups.

PMID- 18039895
TI  - Immunohistochemical expression of vascular endothelial growth factor and vascular
      endothelial growth factor receptor associated with tumor cell proliferation in
      canine cutaneous squamous cell carcinomas and trichoepitheliomas.
AB  - The expression of 5 markers associated with angiogenesis was studied in canine
      squamous cell carcinomas (SCCs) (n = 19) and canine trichoepitheliomas (TCPs) (n
      = 24). SCCs were assigned histologic grades, and tissue sections from both tumor
      types were immunohistochemially stained for the expression of vascular
      endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2
      (VEGFR-2), as well as intratumoral microvessel density (iMVD), tumor
      proliferation index (PI), and tumor apoptotic index (AI), using antibodies
      against VEGF, VEGFR-2, von Willebrand's factor, Ki-67 antigen, and the terminal
      deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate end
      labeling method (TUNEL), respectively. VEGF and VEGFR-2 were detected in 17/19
      (89.4%) and 19/19 (100%) SCCs and in 17/24 (70.8%) and 20/24 (83.3%) TCPs,
      respectively. In SCCs, there was substantial correlation between histologic grade
      and PI (r = 0.51); and moderate correlation between VEGF and histologic grade (r
      = 0.43), VEGFR-2 and histologic grade (r = 0.47), VEGF and PI (r = 0.47), and
      VEGFR-2 and PI (r = 0.47) (Spearman rank correlation coefficient). In TCPs, there
      was substantial correlation between VEGF and PI (r = 0.51) and a moderate
      correlation between VEGFR-2 and iMVD (r = 0.36). The median iMVD of SCCs (15.5)
      was significantly higher than the median iMVD of TCPs (9.05) (P value < .05). It
      was concluded that VEGF and VEGFR-2 may promote tumor cell proliferation in TCPs
      and SCCs. An autocrine pathway for VEGF probably operates in canine SCCs and
      TCPs, as VEGF and VEGFR-2 expression was found in most tumors and was associated
      with evidence for tumor cell proliferation.

PMID- 18039896
TI  - Naturally occurring parvovirus-associated feline hypogranular cerebellar
      hypoplasia-- A comparison to experimentally-induced lesions using
      immunohistology.
AB  - Three cases of feline cerebellar hypoplasia are presented. At the time of
      examination, the ages of the cats ranged from 2 months to 1 year. Necropsy
      revealed cerebellar and pons hypoplasia. Polymerase chain reaction for parvoviral
      deoxyribonucleic acid was positive in cerebellar tissue. Cell-specific
      immunolabeling was used to characterize the lesions, which were characterized
      into 2 types. In type 1 lesions, the cortex was nearly agranular, with an
      extremely thin molecular layer; the Purkinje cells were randomly placed and
      oriented, and their stunted main dendrite produced a thorn-covered atrophic
      dendritic tree; the basket cell axons ran randomly and had dysmorphic endings;
      and myelinated fibers were severely reduced in folia axes. In type 2 lesions, the
      cortex was hypogranular; the Purkinje cells were linearly organized, but their
      main dendrite extended too far in the molecular layer before giving up smooth,
      bent secondary dendrites; many basket cells were located along the cerebellar
      surface, and their axons ran at right angle to the surface; myelinated fibers
      were moderately reduced. Defects in climbing fiber synapse translocation and
      elimination were evident in both types of lesion. This immunohistologic study
      allowed a comparison between lesions in these spontaneous cerebellar hypoplasia
      cases with those documented when using silver impregnation studies after
      perinatal experimental cerebellar damage. Such a comparison is consistent with
      viral infection that occurs before birth in all 3 cases. Progress in parvovirus
      biology knowledge suggests that viral NS1 protein cytotoxicity might explain
      degenerative changes in the Purkinje cells that were present, in addition to the
      development defect.

PMID- 18039897
TI  - Mammary invasive micropapillary carcinoma in cats: clinicopathologic features and
      nuclear DNA content.
AB  - Invasive micropapillary carcinoma (IMC) is a variant of infiltrating ductal
      carcinoma of the breast associated with poor outcome. In this study, we report 16
      carcinomas of the feline mammary gland displaying histologic features that
      correspond to IMC of the breast in women. The clinicopathologic findings, overall
      survival time, disease-free survival time, and nuclear DNA content of these cats
      were compared with 65 more common invasive mammary carcinomas (other feline
      mammary carcinoma [FMC]) of nonspecified type. IMC was associated with larger
      tumor size, higher histologic grade (P < .0001), deeper muscle invasion (P =
      .004), and more frequent lymphovascular invasion and nodal metastases (P = .009
      and P = .001, respectively) than other FMCs. The aneuploid pattern was more
      frequent in IMC lesions. IMCs were also associated with lower survival rates. In
      summary, all cases of feline IMC were associated with clinicopathologic features
      of high biologic aggressiveness and should be classified as independent
      histologic types of FMC.

PMID- 18039898
TI  - Equine multinodular pulmonary fibrosis: a newly recognized herpesvirus-associated
      fibrotic lung disease.
AB  - Pulmonary fibrosis and interstitial lung disease are poorly understood in horses;
      the causes of such conditions are rarely identified. Equine herpesvirus 5 (EHV-5)
      is a gamma-herpesvirus of horses that has not been associated with disease in
      horses. Pathologic and virologic findings from 24 horses with progressive nodular
      fibrotic lung disease associated with EHV-5 infection are described and compared
      with 23 age-matched control animals. Gross lesions consisted of multiple nodules
      of fibrosis throughout the lungs. Histologically, there was marked interstitial
      fibrosis, often with preservation of an "alveolar-like" architecture, lined by
      cuboidal epithelial cells. The airways contained primarily neutrophils and
      macrophages. Rare macrophages contained large eosinophilic intranuclear viral
      inclusion bodies; similar inclusion bodies were also found cytologically. The
      inclusions were identified as herpesviral-like particles by transmission electron
      microscopy in a single horse. In situ hybridization was used to detect EHV-5
      nucleic acids within occasional macrophage nuclei. With polymerase chain reaction
      (PCR), the herpesviral DNA polymerase gene was detected in 19/24 (79.2%) of
      affected horses and 2/23 (8.7%) of the control horses. Virus genera-specific PCR
      was used to detect EHV-5 in all of the affected horses and none of the control
      horses. EHV-2 was detected in 8/24 (33.3%) of affected horses and 1/9 (11.1%) of
      the control horses. This disease has not been reported before, and the authors
      propose that based upon the characteristic gross and histologic findings, the
      disease be known as equine multinodular pulmonary fibrosis. Further, we propose
      that this newly described disease develops in association with infection by the
      equine gamma-herpesvirus, EHV-5.

PMID- 18039899
TI  - Lesion development and immunohistochemical changes in granulomas from cattle
      experimentally infected with Mycobacterium bovis.
AB  - Mycobacterium bovis, the causative agent of bovine tuberculosis, persists within
      granulomas. Formation of granulomas involves a complex array of immune activation
      and cellular migration. To examine temporal changes in granuloma development, we
      inoculated 32 cattle with M. bovis of deer origin. Tissues from 4 calves each
      were examined at 15, 28, 42, 60, 90, 180, 270, and 370 days after inoculation.
      Granulomas in the medial retropharyngeal lymph node were staged (I-IV) on the
      basis of cellular composition and the presence or absence of necrosis and
      peripheral fibrosis. Immunohistochemistry for inducible nitric oxide synthase
      (iNOS), CD68, CD4, CD8, and gamma/delta T cells was performed. Fifteen days after
      inoculation only stage I granulomas were seen, while between 28 and 60 days,
      there was a steady progression through granuloma stages such that by day 60,
      granulomas of all 4 stages were seen. Acid-fast bacilli were present in moderate
      to-large numbers in stage I granulomas 15-60 days after inoculation. Stage IV
      granulomas contained large numbers of acid-fast bacteria. Abundant iNOS
      immunoreactivity was associated with granulomas from day 15 through day 60 but
      was minimal from day 90 to the termination of the experiment. The relative number
      of CD4+ and CD68+ cells remained constant throughout the study. In contrast, at
      time points >60 days, numbers of CD8+ and gamma/delta T cells diminished.
      Tuberculous granulomas are dynamic lesions that follow an orderly progression
      through disease stages. Diminished expression of iNOS and reduced numbers of CD8+
      and gamma/delta T cells late in the progression of tuberculous granulomas may
      represent a failure of the host response to control infection.

PMID- 18039900
TI  - Immunohistochemical detection of multiple myeloma 1/interferon regulatory factor
      4 (MUM1/IRF-4) in canine plasmacytoma: comparison with CD79a and CD20.
AB  - Multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) is
      involved in lymphoid cell differentiation, particularly in the production of
      plasma cells. We examined the immunoreactivity of mouse monoclonal antibody Mum
      1p to MUM1/IRF4 and compared it with expression of CD79a and CD20 in 109
      plasmacytomas in 107 dogs. Tissues had been fixed in formalin and embedded in
      paraffin. One hundred one of 109 (93.5%) tumors were positive for MUM1/IRF4. The
      staining was nuclear with weak cytoplasmic reaction. Fifty-nine of 105 (56.2%)
      plasmacytomas were positive for CD79a; only 21 of 108 (19.4%) cases were positive
      for CD20. MUM1/IRF4 staining was performed on 139 other tumors including B- and T
      cell lymphomas, histiocytic proliferations, mast cell tumors, and melanocytic
      tumors. The only MUM1/IRF4-positive nonplasmacytic tumors were 10 B-cell
      lymphomas and 1 anaplastic lymphoma. We conclude the following: 1) Antibody Mum
      1p is very specific for canine plasmacytomas, 2) antibody Mum-1p is superior in
      sensitivity and specificity to CD79a and CD20 for the identification of canine
      plasmacytomas in formalin-fixed, paraffin-embedded tissues, 3) canine lymphomas
      that express MUM1/IRF4 are few and usually of B-cell origin, 4) other canine
      leukocytic and melanocytic tumors do not express MUM1/IRF4, and 5) prospective
      studies are needed to determine whether the expression of MUM1/IRF4, particularly
      in lymphomas, has prognostic significance.

PMID- 18039901
TI  - Nasal and nasopharyngeal lymphoma in cats: 50 cases (1989-2005).
AB  - Lymphoma is the most common nasal cavity tumor in cats, yet few reports
      specifically address the anatomic, immunohistologic, and cytologic features of
      this neoplasm. Fifty cats were diagnosed with lymphoma at necropsy, via biopsy or
      by cytology alone. Ten cats displayed multiorgan involvement, and in 2 of these
      the involvement was limited to the cerebellum and frontal cortex, respectively.
      Of the tumors, 41 of 50 (82%) were classified as nasal lymphoma, 5 of 50 (10%)
      were classified as nasopharyngeal lymphoma, and 4 of 50 (8%) involved both nasal
      and nasopharyngeal tissue. Histologically, all were considered diffuse lymphoid
      neoplasms and no cats displayed features of follicular lymphoma. Of the 44 cases
      available for slide review by the pathologist, 40 of 44 (91%) were classified as
      immunoblastic lymphoma, 2 of 44 (5%) as diffuse large cell, and 1 as diffuse
      mixed; 1 was unclassified. Of the 45 cats for which immunohistochemical stains
      were available, 32 were uniformly positive for CD79a, 7 were uniformly CD3
      positive, and 6 had a mixed population of CD79a and CD3 cells. Epithelioptropism
      was exhibited in 4 of 5 (80%) cats in which there was sufficient epithelium
      present for evaluation. Of those 4, 3 were B-cell and 1 was a granulated T-cell
      lymphoma. In the 21 cats which nasal cytology was performed, 15 were
      cytologically diagnosed with lymphoma; the diagnoses in the remaining five cats
      were inflammatory (n = 4), normal lymphoid tissue (n = 1), or nondiagnostic (n =
      1). The most common biochemical abnormalities were panhyperproteinemia in 26/46
      (57%) of cats and hypocholesterolemia in 11/46 (24%) of cats.

PMID- 18039902
TI  - Expression of the embryonic transcription factor Oct4 in canine neoplasms: a
      potential marker for stem cell subpopulations in neoplasia.
AB  - Neoplastic cells and stem cells share several phenotypic characteristics.
      Recently, numerous studies have identified adult stem cells that have been
      hypothesized to be the cellular origin for cancer in several tissues. Oct4 has
      been consistently associated with pluripotent or stemlike cells, and it is
      hypothesized that Oct4 is necessary for the maintenance of pluripotency. We
      hypothesize that Oct4-positive cells are present in all canine neoplasms and that
      these subpopulations of neoplastic cells might represent "cancer stem" cells. To
      test this hypothesis, 83 canine neoplasms representing 21 neoplastic diseases
      were evaluated for Oct4 expression using immunohistochemistry. The results of
      this study showed that all tumors included in this study contained a
      subpopulation of Oct4-positive cells, although the proportion of Oct4-positive
      cells and the intensity of immunoreactivity varied both within and between tumor
      types. Subpopulations of Oct4-positive cells identified in these tumors are
      likely to represent "cancer stem" cells and therefore might be responsible for
      the maintenance and propagation of the tumors. If these cells represent cancer
      stem cells, and are therefore responsible for the maintenance and growth of the
      neoplastic cellular population, then these cells should serve as relevant
      therapeutic targets and offer the greatest potential for curative treatment.

PMID- 18039903
TI  - A soluble secreted glycoprotein (eCLCA1) is overexpressed due to goblet cell
      hyperplasia and metaplasia in horses with recurrent airway obstruction.
AB  - The equine putative chloride channel protein eCLCA1 is thought to be critically
      involved in the pathogenesis of recurrent airway obstruction (RAO) via modulation
      of the hydration of airway mucins. A recent study revealed a strong increase of
      eCLCA1 messenger ribonucleic acid (mRNA) in the lungs of horses with RAO. In this
      study, eCLCA1 protein and mRNA expression were quantified in airway goblet cells
      of 9 horses affected with RAO and 9 control horses by using immunohistochemistry
      and laser microdissection followed by real-time quantitative reverse
      transcription polymerase chain reaction, respectively. Horses affected by RAO had
      strong goblet cell metaplasia in bronchioles and goblet cell hyperplasia in
      bronchi and the trachea. Expression of the eCLCA1 protein was tightly linked to
      all airway goblet cells in both groups. No differences were detected in the ratio
      of eCLCA1 mRNA copy numbers to the mRNA copy numbers of the housekeeping gene EF
      1a per goblet cell between horses affected with RAO and unaffected horses,
      suggesting that the increase in eCLCA1 expression is because of increased numbers
      of goblet cells and not transcriptional upregulation of the eCLCA1 gene. In
      addition, biochemical analyses of the eCLCA1 protein after in vitro translation
      and heterologous expression in cultured cells revealed that eCLCA1 is a secreted
      glycoprotein and not an integral membrane protein. Taken together, the results
      suggest that eCLCA1 mediates its effect as a soluble constituent of airway mucins
      that is overexpressed in RAO airways because of goblet cell hyperplasia and
      metaplasia, not transcriptional upregulation.

PMID- 18039904
TI  - Leukoencephalomyelopathy in specific pathogen-free cats.
AB  - Investigations were carried out on 8 specific pathogen-free cats (5 male and 3
      female) from a colony experiencing "outbreaks" of progressive hind limb ataxia in
      190 of 540 at-risk animals ranging from 3 months to 3 years old. These studies
      identified moderate to severe bilateral axonal degeneration within white matter
      regions of the cervical, thoracic, and lumbar spinal cord and in the white matter
      of the cerebral internal capsule and peduncle, in the roof of the fourth
      ventricle and inferior cerebellar peduncle, and in the external arcuate and
      pyramidal fibres of the medulla. There were varying degrees of accompanying
      microgliosis, astrocytosis, and capillary hyperplasia. Such a clinicopathologic
      syndrome, termed feline leukoencephalomyelopathy, has previously been described
      in cat colonies in Britain and New Zealand, although its etiology has not been
      determined. The degenerative nature of the lesions and their bilateral
      distribution suggest possible nutritional, metabolic, or toxic causes. Although
      these findings provide circumstantial evidence that the exclusive feeding of a
      gamma-irradiated diet of reduced vitamin A content is associated with the
      development of the neuronal lesions, further tissue micronutrient and antioxidant
      analysis will be required to support this hypothesis.

PMID- 18039905
TI  - Granulomatous and eosinophilic rhinitis in a cow caused by Pseudallescheria
      boydii species complex (Anamorph Scedosporium apiospermum).
AB  - A 2-year-old Hereford cow was presented to the teaching hospital for increased
      respiratory noise and bilateral bloody nasal discharge. A nodular rhinitis was
      detected clinically, and the nasal biopsy revealed a granulomatous and
      eosinophilic rhinitis with intralesional fungi. The cow was euthanized due to
      financial constraints. Grossly multifocal-to-coalescing, raised, ulcerated firm
      nodules were present in both nares. Histologically, the lamina propria was
      expanded by intense infiltrates of eosinophils, epithelioid macrophages,
      multinucleate giant cells, lymphocytes, and plasma cells. Associated with the
      inflammatory cells were variably sized, septate hyphae, 5-8 microm in diameter,
      admixed with numerous, terminal conidia, 6-30 microm in diameter, with a discrete
      outer wall identified by culture as Pseudallescheria boydii species complex
      (anamorph Scedosporium apiospermum). The infection was localized to the nasal
      cavity with no gross or microscopic evidence of a systemic dissemination.

PMID- 18039906
TI  - Pulmonary lymphomatoid granulomatosis in a dog: evidence of immunophenotypic
      diversity and relationship to human pulmonary lymphomatoid granulomatosis and
      pulmonary Hodgkin's disease.
AB  - We describe a 10-month-old, intact female American Cocker Spaniel with pulmonary
      lymphomatoid granulomatosis (PLG). On clinical examination, this dog presented
      with nonproductive dry cough, serous nasal discharge, dyspnea, and lack of
      appetite. Radiography showed a consolidated lesion in the left cranial lung lobe.
      Histopathologic examination showed a mixed population of atypical lymphoid cells
      that had infiltrated into the pulmonary blood vessels angiocentrically. The
      lymphocytes were CD3 positive, consistent with a pan-T-cell phenotype. The
      lymphoid cells in the lesion were also positive for CD20cy and CD79a, indicative
      of the presence of B cells. We also observed large Reed-Sternberg-like cells that
      were positive for CD15 and CD30, similar to observations in human pulmonary
      Hodgkin's disease (PHD). In conclusion, canine PLG in this Cocker Spaniel was
      associated with B and T cells, which is first identified in a case of canine PLG.
      It was histopathologically similar to human lymphomatoid granulomatosis and
      immunophenotypically similar to human PHD.

PMID- 18039907
TI  - Feline cutaneous viral papilloma associated with human papillomavirus type 9.
AB  - A 12-year-old domestic Shorthaired cat developed a multinodular exophytic mass on
      the dorsal surface of the nose. The skin surrounding the mass was nonpigmented,
      and actinic keratosis had been diagnosed in this area 3 years previously.
      Histologic examination revealed hyperkeratosis, epidermal hyperplasia,
      papillomatosis, koilocytosis, and possible intranuclear viral inclusions.
      Polymerase chain reaction amplified papillomaviral deoxyribonucleic acid from
      formalin-fixed samples of the lesion. Sequencing of the amplicon revealed 98%
      similarity to human papillomavirus (HPV) type 9. To the authors' knowledge, this
      is only the second reported feline cutaneous viral papilloma. In addition, this
      is the first report of a feline papilloma being associated with an HPV.

PMID- 18039908
TI  - Mimosa tenuiflora as a cause of malformations in ruminants in the northeastern
      Brazilian semiarid rangelands.
AB  - Craniofacial anomalies, eye malformations, and permanent flexures of the
      forelimbs are common malformations seen in ruminants grazing semiarid rangelands
      of Northeastern Brazil. To investigate the cause of these malformations, we fed 2
      suspected plants, Mimosa tenuiflora or Prosopis juliflora, to groups of 4
      pregnant goats each. Fresh green M. tenuiflora was collected daily and fed ad
      libitum to 4 goats in group 1 throughout pregnancy. This treatment group also
      received a supplemental feed concentrate equivalent to 1% body weight. Four goats
      in group 2 received a ration with 70% of P. juliflora pods and 30% hay throughout
      pregnancy. Four control goats were fed supplemental feed concentrate (1% body
      weight) and hay ad libitum throughout pregnancy. Goats treated with P. juliflora
      pods and the control goats delivered 9 normal kids. The four goats that were fed
      M. tenuiflora during pregnancy delivered 4 kids, 3 of which had abnormalities
      similar to those observed in field cases, including cleft lip, unilateral corneal
      opacity, ocular bilateral dermoids, buphthalmos with a cloudy brownish appearance
      of the anterior chamber due to an iridal cyst, and segmental stenosis of the
      colon. Malformations induced experimentally by M. tenuiflora were similar to
      those observed in field cases, suggesting that M. tenuiflora is a cause of the
      field cases observed in the Brazilian semiarid rangelands.

PMID- 18039909
TI  - Calcium diacylglycerol guanine nucleotide exchange factor I (CalDAG-GEFI) gene
      mutations in a thrombopathic Simmental calf.
AB  - Simmental thrombopathia is an inherited platelet disorder that closely resembles
      the platelet disorders described in Basset Hounds and Eskimo Spitz dogs.
      Recently, two different mutations in the gene encoding calcium diacylglycerol
      guanine nucleotide exchange factor I (CalDAG-GEFI) were described to be
      associated with the Basset Hound and Spitz thrombopathia disorders, and a third
      distinct mutation was identified in CalDAG-GEFI in thrombopathic Landseers of
      European Continental Type. The gene encoding CalDAG-GEFI was sequenced using DNA
      obtained from normal cattle and from a thrombopathic calf studied in Canada. The
      affected calf was found to have a nucleotide change (c.701 T>C), which would
      result in the substitution of a proline for a leucine within structurally
      conserved region two (SCR2) of the catalytic domain of the protein. This change
      is likely responsible for the thrombopathic phenotype observed in Simmental
      cattle and underscores the critical nature of this signal transduction protein in
      platelets.

PMID- 18039910
TI  - Histologic and immunohistochemical characterization of a testicular mixed germ
      cell sex cord-stromal tumor and a leydig cell tumor in a dog.
AB  - Mixed germ cell sex cord-stromal tumors (MGSCTs) of the testis are rare in dogs.
      We describe the histopathology and immunohistochemical characteristics of an
      MGSCT associated with a Leydig cell tumor in a cryptorchid testis.
      Histologically, MGSCT consisted of two nodules of seminiferous tubules lined by
      germ cells and Sertoli cells in variable proportions. Germ cells had variable
      size and nuclear features, with frequent giant cells. Germ cells were evenly
      mixed with Sertoli cells or located in the center of tubules. Markers that
      labeled mainly germ cells and few or no Sertoli or Leydig cells were calretinin,
      KIT, and PGP 9.5. E-cadherin, GATA-4, inhibin-alpha (INH-alpha), and neuron
      specific enolase (NSE) were predominantly detected in Sertoli cells, whereas
      melan A was particularly expressed in Leydig cells and vimentin in all three cell
      types. OCT3/4 was not detected in any cell type. Although more cases of canine
      MGSCT need to be examined, our results suggest that an immunohistochemical panel
      of E-cadherin, GATA-4, INH-alpha, KIT, NSE, PGP 9.5, and melan A will help
      distinguish the three main cell types in canine testicular germ cell and sex cord
      stromal tumors.

PMID- 18039911
TI  - Immunohistochemical demonstration of the putative canine distemper virus receptor
      CD150 in dogs with and without distemper.
AB  - Signaling lymphocyte activation molecule (SLAM) or CD150 can function as a
      receptor for the canine distemper virus (CDV) in vitro. The expression of SLAM
      was studied using immunohistochemistry in order to evaluate the presence and
      distribution of the receptor in dogs in vivo. Additionally, receptor expression
      was assessed after experimental infection of dogs with CDV. In 7 control dogs
      without distemper virus, the receptor was found in various tissues, mostly on
      cells morphologically identified as lymphocytes and macrophages. In 7 dogs with
      early distemper lesions characterized by presence of the virus, higher numbers of
      SLAM-expressing cells were found in multiple tissues recognized as targets of CDV
      compared with those in control dogs. These findings suggest that SLAM, a putative
      distemper receptor, is expressed in dogs in vivo. Additionally, virus infection
      is associated with up-regulation of SLAM, potentially causing an amplification of
      virus in the host.

PMID- 18039912
TI  - Congenital unilateral absence of the corticospinal tract in a Siamese cat.
AB  - A Siamese kitten presented with mild gait dysfunction associated with periodic
      circling. Pathologic investigation revealed unilateral (right-sided) absence of
      the corticospinal (pyramidal) tract throughout its normal course. Although an
      infectious cause cannot be completely ruled out a genetic etiology was suspected.

PMID- 18039913
TI  - Subcutaneous neoplasms of the ventral abdomen with features of adrenocortical
      tumors in two ferrets.
AB  - A ventral abdominal subcutaneous mass was removed from each of 2 young adult
      spayed female ferrets. In both cases, the neoplasms were composed of islands of
      polygonal cells separated by interlacing streams of spindloid cells reminiscent
      of ferret adrenocortical tumors with smooth muscle proliferation.
      Immunohistochemically, the polygonal cells demonstrated strong cytoplasmic
      reactivity for inhibin and weak cytoplasmic reactivity for pancytokeratin and S
      100 protein. Spindloid cells demonstrated strong cytoplasmic reactivity for alpha
      smooth muscle actin, muscle-specific actin, desmin, and glial fibrillary acidic
      [corrected] protein. Ultrastructurally, the polygonal cells contained numerous
      intracytoplasmic clear vacuoles, mitochondria, scant rough endoplasmic reticulum,
      and few intermediate filaments. In one tumor, vesicular tubular mitochondria were
      found in polygonal cells. The spindloid cells contained numerous aggregates of
      parallel intermediate filaments. The histologic, immunohistochemical, and
      ultrastructural findings are suggestive of adrenocortical tumors with smooth
      muscle proliferation, but cannot be differentiated from an ovarian gonadal
      stromal tumor. Neither ferret had a clinically detected primary adrenal gland
      tumor or clinical signs of adrenal-associated endocrinopathy.

PMID- 18039914
TI  - Sarcocystis neurona encephalitis in a dog.
AB  - A 1.5-year-old male Feist dog was presented to a veterinarian for reluctance to
      stand on the hind legs. Treatment included dexamethasone and resulted in a
      favorable initial response, but posterior paresis returned and progressed to
      recumbency, hyperesthesia, and attempts to bite the owner. The dog was
      euthanized. The brain was negative for rabies by fluorescent antibody analysis.
      Multiple foci of encephalitis were found in the cerebrum and particularly in the
      cerebellum. Protozoa morphologically consistent with Sarcocystis sp. were
      identified at sites of intense inflammation and malacia. Additionally, multiple
      schizonts were identified in areas without inflammation. Immunohistochemistry
      using both polyclonal and monoclonal antibodies specific for Sarcocystis neurona
      was strongly positive. No reaction to polyclonal antisera for Toxoplasma gondii
      or Neospora caninum was found. Polymerase chain reaction confirmed that the
      protozoa were S. neurona. Additional aberrant hosts for S. neurona other than
      horses have been identified, but S. neurona encephalitis has not been documented
      previously in the dog.

PMID- 18039915
TI  - Over 60% of NIH extramural funding involves animal-related research.

PMID- 18039916
TI  - Hamster check pouch--not a mucosal surface!

PMID- 18039917
TI  - Novel chimeric genotype 1b/2a hepatitis C virus suitable for high-throughput
      screening.
AB  - A major obstacle in hepatitis C virus (HCV) research has been the lack of a
      permissive cell culture system that produces infectious viral particles.
      Significant breakthroughs have been achieved lately in establishing such culture
      systems. Yet to date, there are no reports of the applications of any of these
      systems in HCV drug screening. Here, we report the generation of two
      monocistronic, chimeric genotype 1 full-length HCV genome molecules. These
      molecules, C33J-Y835C-UBI and C33J-Y835C-FMDV2A, both contain the structural
      protein region from genotype 1 (subtype 1b, Con1) and the remaining region from
      the genotype 2a (JFH1) clone. Both contain the humanized Renilla luciferase
      reporter gene which is separated from the rest of the HCV open reading frame by
      two different cleavage sites. The viral RNAs replicated efficiently in
      transfected cells. Viral particles produced were infectious in naive Huh7.5
      cells, and the infectivity could be blocked by monoclonal antibody against a
      putative HCV entry cofactor, CD81. A pilot high-throughput screen of 900 unknown
      compounds was executed by both the genotype 2a subgenomic replicon system and the
      infectious system. Thirty-one compounds were identified as hits by both systems,
      whereas 78 compounds were identified as hits only for the infectious system,
      suggesting that the infectious system is capable of identifying inhibitors
      targeting the viral structural proteins and steps involving them in the viral
      life cycle. The infectious HCV system developed here provides a useful and
      versatile tool which should greatly facilitate the identification of HCV
      inhibitors currently not identified by the subgenomic replicon system.

PMID- 18039918
TI  - Effect of resiquimod 0.01% gel on lesion healing and viral shedding when applied
      to genital herpes lesions.
AB  - Resiquimod, a Toll-like receptor 7/8 agonist developed as a topical treatment to
      decrease recurrences of anogenital herpes, induces proinflammatory cytokines that
      may delay lesion healing. Adults with frequently recurring anogenital herpes were
      randomized within 24 h of onset of a recurrence to vehicle or resiquimod 0.01%
      gel two times per week for 3 weeks. Subjects underwent daily lesion assessments
      and sampling for herpes simplex virus DNA PCR for 21 days or until investigator
      determined healing of lesion(s). Eighty-two subjects with a mean age of 39 +/-
      10.5 years and a median of seven recurrences per year were enrolled in the study.
      The qualifying recurrence was positive by PCR for herpes simplex virus in 68% of
      subjects. No difference was observed between the vehicle (39 subjects) and
      resiquimod (43 subjects) groups with respect to time to healing (median of 7.0
      days versus median of 6.5 days, respectively; Cox proportional hazard model ratio
      of 1.229; 95% confidence interval, 0.778 to 1.942; P = 0.376). The distributions
      of maximum severity scores for any investigator-assessed local skin signs and for
      subject-assessed local symptoms were similar between treatment groups (P = 0.807
      and P = 0.103, respectively). For subjects with at least one positive PCR result,
      no difference was observed for time to cessation of viral shedding (median of 7
      days versus median of 5 days for vehicle and resiquimod groups, respectively; Cox
      proportional hazard model ratio of 1.471; 95% confidence interval, 0.786 to
      2.754; P = 0.227). Application of resiquimod 0.01% two times per week for 3 weeks
      did not delay the healing of genital herpes lesions or reduce acute viral
      shedding.

PMID- 18039919
TI  - In vitro antifungal susceptibilities of five species of sporothrix.
AB  - Ninety-two isolates belonging to five species of the Sporothrix schenckii complex
      were tested in vitro against 12 antifungal agents, using a reference
      microdilution method. There were significant differences among the species;
      Sporothrix brasiliensis was the species that showed the best response to
      antifungals, and S. mexicana had the worst response. In general, terbinafine was
      the most active drug, followed by ketoconazole and posaconazole.

PMID- 18039920
TI  - Cytotoxic activity of N-chlorotaurine on Acanthamoeba spp.
AB  - Acanthamoeba spp. are the causative agents of Acanthamoeba keratitis (AK), which
      mainly occurs in contact lens wearers, and of skin lesions, granulomatous amoebic
      encephalitis (GAE), and disseminating diseases in the immunocompromised host. AK
      therapy is complex and irritating for the eye, skin lesions are difficult to
      treat, and there is no effective treatment for GAE. Therefore, new anti
      Acanthamoeba drugs are needed. We investigated the anti-Acanthamoeba activity of
      N-chlorotaurine (NCT), an endogenous mild antiseptic. It was shown that NCT has
      amoebicidal qualities, both in phosphate-buffered saline (PBS) and in amoebic
      culture medium. After 6 h of treatment with 10 mM NCT in PBS, the levels of
      trophozoites of all strains investigated already showed at least a 2-log
      reduction. When the trophozoites were treated with 20 mM NCT in culture medium,
      they showed a 2-log reduction after 24 h. The addition of NH(4)Cl to NCT led to a
      faster decrease in the numbers of living cells, if tests were carried out in PBS.
      A delay of excystation was observed when cysts were treated with 55 mM (1%) NCT
      in culture medium. A complete failure of excystment was the result of treatment
      with 1% NCT plus 1% NH(4)Cl in PBS. Altogether, NCT clearly demonstrated
      amoebicidal activity at concentrations well tolerated by human tissues and might
      be useful as a topical drug for the treatment of Acanthamoeba infections. The
      addition of ammonium chloride can be considered to enhance the activity.

PMID- 18039921
TI  - NS3 Peptide, a novel potent hepatitis C virus NS3 helicase inhibitor: its
      mechanism of action and antiviral activity in the replicon system.
AB  - Hepatitis C virus (HCV) chronic infections represent one of the major and still
      unresolved health problems because of low efficiency and high cost of current
      therapy. Therefore, our studies centered on a viral protein, the NS3 helicase,
      whose activity is indispensable for replication of the viral RNA, and on its
      peptide inhibitor that corresponds to a highly conserved arginine-rich sequence
      of domain 2 of the helicase. The NS3 peptide (p14) was expressed in bacteria. Its
      50% inhibitory activity in a fluorometric helicase assay corresponded to 725 nM,
      while the ATPase activity of NS3 was not affected. Nuclear magnetic resonance
      (NMR) studies of peptide-protein interactions using the relaxation filtering
      technique revealed that p14 binds directly to the full-length helicase and its
      separately expressed domain 1 but not to domain 2. Changes in the NMR chemical
      shift of backbone amide nuclei ((1)H and (15)N) of domain 1 or p14, measured
      during complex formation, were used to identify the principal amino acids of both
      domain 1 and the peptide engaged in their interaction. In the proposed interplay
      model, p14 contacts the clefts between domains 1 and 2, as well as between
      domains 1 and 3, preventing substrate binding. This interaction is strongly
      supported by cross-linking experiments, as well as by kinetic studies performed
      using a fluorometric assay. The antiviral activity of p14 was tested in a
      subgenomic HCV replicon assay that showed that the peptide at micromolar
      concentrations can reduce HCV RNA replication.

PMID- 18039922
TI  - Factors associated with the selection of mutations conferring resistance to
      protease inhibitors (PIs) in PI-experienced patients displaying treatment failure
      on darunavir.
AB  - The objective of this study was to characterize the mutations selected by
      darunavir (DRV) use in protease inhibitor (PI)-experienced patients and the
      associated factors. We analyzed treatment failure in 54 PI-experienced human
      immunodeficiency virus (HIV)-infected patients on a DRV- and ritonavir-containing
      regimen. Viral genotyping was carried out at the baseline, at between 1 and 3
      months of treatment, and at between 3 and 6 months of treatment to search for the
      selection of mutations conferring resistance to PIs. The median baseline HIV RNA
      level was 4.9 log(10) copies/ml, and the median CD4 count was 87 cells/mm(3). At
      the baseline, the median numbers of resistance mutations were as follows: 3 DRV
      resistance mutations, 4 major PI resistance mutations, and 10 minor PI resistance
      mutations. The most common mutations that emerged at rebound included V32I (44%),
      I54M/L (24%), L33F (25%), I84V (21%), and L89V (12%). Multivariate analysis
      showed that higher baseline HIV RNA levels and smaller numbers of nucleoside
      reverse transcriptase inhibitor simultaneously used with DRV were associated with
      a higher risk of DRV resistance mutation selection. By contrast, L76V, a known
      DRV resistance mutation, was found to decrease the risk of selection of another
      DRV resistance mutation. The occurrence of virological failure while a patient
      was on DRV was associated with the selection of mutations that increased the
      level of DRV resistance without affecting susceptibility to tipranavir (TPV). In
      these PI-treated patients who displayed treatment failure while they were on a
      DRV-containing regimen, we confirmed the set of emerging mutations associated
      with DRV failure and identified the factors associated with the selection of
      these mutations. TPV susceptibility does not seem to be affected by the selection
      of a DRV resistance mutation.

PMID- 18039923
TI  - Inhibitory activities of 11 antimicrobial agents and bactericidal activities of
      vancomycin and daptomycin against invasive methicillin-resistant Staphylococcus
      aureus isolates obtained from 1999 through 2006.
AB  - We assessed MICs and minimal bactericidal concentrations of vancomycin,
      daptomycin, and nine other antimicrobials against methicillin-resistant
      Staphylococcus aureus isolates obtained from 1999 through 2006. No vancomycin,
      daptomycin, or linezolid resistance was observed. Clindamycin, gentamicin, and
      ciprofloxacin resistance decreased significantly. No tolerance to vancomycin or
      daptomycin was observed, nor was MIC creep seen.

PMID- 18039924
TI  - In vitro activity of cefpodoxime, an expanded-spectrum cephalosporin, against
      Salmonella enterica serotype typhi.

PMID- 18039925
TI  - Chronic kidney disease after nonrenal solid-organ transplantation.
AB  - Chronic kidney disease (CKD) is a common complication after nonrenal solid-organ
      transplantation. The risk for CKD is influenced by many factors, some of which
      have a direct impact on how such patients are treated in the pre-, peri-, and
      posttransplantation settings. This review describes hazards for acute and chronic
      kidney injury, with particular emphasis on calcineurin inhibitor-mediated
      nephrotoxicity. Rather than a detailed description of management issues that are
      common to the general CKD population, highlighted are aspects that are more
      specific to nonrenal solid-organ transplant recipients with a focus on liver,
      heart, and lung recipients. Strategies to minimize nephrotoxic insults and retard
      progressive renal injury are discussed, as are issues that are pertinent to
      dialysis and transplantation. Finally, future approaches to prevent and treat CKD
      without compromising function of the transplanted organ are addressed.

PMID- 18039926
TI  - Epistatic connections between microphthalmia-associated transcription factor and
      endothelin signaling in Waardenburg syndrome and other pigmentary disorders.
AB  - Waardenburg syndrome (WS) is an inherited sensorineural deafness condition in
      humans caused by melanocyte deficiencies in the inner ear and forelock. Mutation
      of microphthalmia-associated transcription factor (MITF) is known to produce WS
      type IIA whereas mutations of either endothelin (EDN) or its receptor endothelin
      receptor B (EDNRB) produce WS type IV. However, a link between MITF
      haploinsufficiency and EDN signaling has not yet been established. Here we
      demonstrate mechanistic connections between EDN and MITF and their functional
      importance in melanocytes. Addition of EDN to cultured human melanocytes
      stimulated the phosphorylation of MITF in an EDNRB-dependent manner, which was
      completely abolished by mitogen-activated protein kinase kinase inhibition. The
      expression of melanocyte-specific MITF mRNA transcripts was markedly augmented
      after incubation with EDN1 and was followed by increased expression of MITF
      protein. Up-regulated expression of MITF was found to be mediated via both the
      mitogen-activated protein kinase-p90 ribosomal S6 kinase-cAMP response element
      binding protein (CREB) and cAMP-protein kinase A-CREB pathways. In addition,
      EDNRB expression itself was seen to be dependent on MITF. The functional
      importance of these connections is illustrated by the ability of EDN to stimulate
      expression of melanocytic pigmentation and proliferation markers in an MITF
      dependent fashion. Collectively these data provide mechanistic and epistatic
      links between MITF and EDN/EDNRB, critical melanocytic survival factors and WS
      genes.

PMID- 18039927
TI  - ATP-binding cassette transporters G1 and G4 mediate cholesterol and desmosterol
      efflux to HDL and regulate sterol accumulation in the brain.
AB  - Transporters in the ABCG family appear to be involved in the cellular excretion
      of cholesterol and other sterols in a cell- and tissue-specific fashion.
      Overexpression of ATP-binding cassette transporters G1 (Abcg1) and G4 (Abcg4) can
      promote cellular cholesterol efflux to high-density lipoprotein (HDL), but the in
      vivo functions of Abcg4 are poorly understood. We used mice with knockouts of
      Abcg1 or Abcg4 singly or together to further elucidate the function of these
      transporters. Abcg1 and Abcg4 are highly expressed in the brain and are found in
      both astrocytes and neurons. Whereas Abcg1(-/-) or Abcg4(-/-) mice showed
      essentially normal levels of brain sterols, in Abcg1(-/-)/Abcg4(-/-) mice, levels
      of several sterol intermediates in the cholesterol biosynthetic pathway, namely
      desmosterol, lathosterol, and lanosterol, as well as 27-OH cholesterol, were
      increased 2- to 3-fold. Overexpression of Abcg1 or Abcg4 promoted efflux of
      desmosterol and cholesterol from cells to HDL, and combined deficiency of these
      transporters led to defective efflux and accumulation of these sterols in primary
      astrocytes. Consistent with defective efflux and sterol accumulation, cholesterol
      biosynthesis was reduced in Abcg1(-/-)/Abcg4(-/-) astrocytes. The accumulation of
      desmosterol, a known liver-X receptor (LXR) activator, was associated with
      increased expression of LXR target genes, including ATP-binding cassette
      transporter A1, and increased apolipoprotein E secretion in Abcg1(-/-)/Abcg4(-/-)
      astrocytes. Our findings provide the first in vivo demonstration of a role for
      Abcg4 in sterol efflux in the brain and show that Abcg1 and Abcg4 have
      overlapping functions in astrocytes, promoting efflux of cholesterol,
      desmosterol, and possibly other sterol biosynthetic intermediates to HDL.

PMID- 18039928
TI  - Synthesis of complement protein C3 in the kidney is an important mediator of
      local tissue injury.
AB  - Increased exposure of the tubular epithelium to filtered protein is a proposed
      mechanism of progressive renal failure associated with glomerular disease, but
      how this protein overload translates into tubular damage remains unclear. We have
      examined a model of adriamycin-induced proteinuria to determine the effect of
      locally synthesized C3, the central proinflammatory protein of the complement
      cascade. C3-/- kidney isografts placed in wild-type C3+/+ mice were protected
      from proteinuria-associated complement activation, tubular damage, and
      progressive renal failure despite the presence of abundant circulating C3. The
      quantity of urinary protein was unaffected by the absence of C3, and thus the
      influence of C3 was not explained by alteration in the filtered protein load.
      These results suggest that local synthesis of complement from renal epithelial
      cells is a critical mediator of tubular damage in proteinuria-associated renal
      disease. Our results concur with previous findings of increased synthesis of C3
      in human tubular epithelium exposed to high concentrations of protein in vitro.
      Because progressive renal damage in humans associates with proteinuria regardless
      of cause, our findings have implications for the pathogenesis and treatment of
      renal failure from many common causes, immunological and nonimmunological.

PMID- 18039929
TI  - Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation
      of cell survival.
AB  - Mitogen-activated protein kinase (MAPK) pathways constitute a large modular
      network that regulates a variety of physiological processes, such as cell growth,
      differentiation, and apoptotic cell death. The function of the ERK pathway has
      been depicted as survival-promoting, in essence by opposing the proapoptotic
      activity of the stress-activated c-Jun NH(2)-terminal kinase (JNK)/p38 MAPK
      pathways. However, recently published work suggests that extracellular regulated
      kinase (ERK) pathway activity is suppressed by JNK/p38 kinases during apoptosis
      induction. In this review, we will summarize the current knowledge about JNK/p38
      mediated mechanisms that negatively regulate the ERK pathway. In particular, we
      will focus on phosphatases (PP2A, MKPs) as inhibitors of ERK pathway activity in
      regulating apoptosis. A model proposed in this review places the negative
      regulation of the ERK pathway in a central position for the cellular decision
      making process that determines whether cells will live or die in response to
      apoptosis-promoting signals. In addition, we will discuss the potential
      functional relevance of negative regulation of ERK pathway activity, for
      physiological and pathological conditions (e.g., cellular transformation).

PMID- 18039930
TI  - Adenovirus RIDalpha regulates endosome maturation by mimicking GTP-Rab7.
AB  - The small guanosine triphosphatase Rab7 regulates late endocytic trafficking.
      Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein-related
      protein 1L (ORP1L) are guanosine triphosphate (GTP)-Rab7 effectors that instigate
      minus end-directed microtubule transport. We demonstrate that RILP and ORP1L both
      interact with the group C adenovirus protein known as receptor internalization
      and degradation alpha (RIDalpha), which was previously shown to clear the cell
      surface of several membrane proteins, including the epidermal growth factor
      receptor and Fas (Carlin, C.R., A.E. Tollefson, H.A. Brady, B.L. Hoffman, and
      W.S. Wold. 1989. Cell. 57:135-144; Shisler, J., C. Yang, B. Walter, C.F. Ware,
      and L.R. Gooding. 1997. J. Virol. 71:8299-8306). RIDalpha localizes to endocytic
      vesicles but is not homologous to Rab7 and is not catalytically active. We show
      that RIDalpha compensates for reduced Rab7 or dominant-negative (DN) Rab7(T22N)
      expression. In vitro, Cu(2+) binding to RIDalpha residues His75 and His76
      facilitates the RILP interaction. Site-directed mutagenesis of these His residues
      results in the loss of RIDalpha-RILP interaction and RIDalpha activity in cells.
      Additionally, expression of the RILP DN C-terminal region hinders RIDalpha
      activity during an acute adenovirus infection. We conclude that RIDalpha
      coordinates recruitment of these GTP-Rab7 effectors to compartments that would
      ordinarily be perceived as early endosomes, thereby promoting the degradation of
      selected cargo.

PMID- 18039931
TI  - Endothelin-converting enzyme-1 regulates endosomal sorting of calcitonin receptor
      like receptor and beta-arrestins.
AB  - Although cell surface metalloendopeptidases degrade neuropeptides in the
      extracellular fluid to terminate signaling, the function of peptidases in
      endosomes is unclear. We report that isoforms of endothelin-converting enzyme-1
      (ECE-1a-d) are present in early endosomes, where they degrade neuropeptides and
      regulate post-endocytic sorting of receptors. Calcitonin gene-related peptide
      (CGRP) co-internalizes with calcitonin receptor-like receptor (CLR), receptor
      activity-modifying protein 1 (RAMP1), beta-arrestin2, and ECE-1 to early
      endosomes, where ECE-1 degrades CGRP. CGRP degradation promotes CLR/RAMP1
      recycling and beta-arrestin2 redistribution to the cytosol. ECE-1 inhibition or
      knockdown traps CLR/RAMP1 and beta-arrestin2 in endosomes and inhibits CLR/RAMP1
      recycling and resensitization, whereas ECE-1 overexpression has the opposite
      effect. ECE-1 does not regulate either the resensitization of receptors for
      peptides that are not ECE-1 substrates (e.g., angiotensin II), or the recycling
      of the bradykinin B(2) receptor, which transiently interacts with beta-arrestins.
      We propose a mechanism by which endosomal ECE-1 degrades neuropeptides in
      endosomes to disrupt the peptide/receptor/beta-arrestin complex, freeing
      internalized receptors from beta-arrestins and promoting recycling and
      resensitization.

PMID- 18039932
TI  - Regulation of Rap1 activity by RapGAP1 controls cell adhesion at the front of
      chemotaxing cells.
AB  - Spatial and temporal regulation of Rap1 is required for proper myosin assembly
      and cell adhesion during cell migration in Dictyostelium discoideum. Here, we
      identify a Rap1 guanosine triphosphatase-activating protein (GAP; RapGAP1) that
      helps mediate cell adhesion by negatively regulating Rap1 at the leading edge.
      Defects in spatial regulation of the cell attachment at the leading edge in
      rapGAP1- (null) cells or cells overexpressing RapGAP1 (RapGAP1(OE)) lead to
      defective chemotaxis. rapGAP1- cells have extended chemoattractant-mediated Rap1
      activation kinetics and decreased MyoII assembly, whereas RapGAP1(OE) cells show
      reciprocal phenotypes. We see that RapGAP1 translocates to the cell cortex in
      response to chemoattractant stimulation and localizes to the leading edge of
      chemotaxing cells via an F-actin-dependent pathway. RapGAP1 localization is
      negatively regulated by Ctx, an F-actin bundling protein that functions during
      cytokinesis. Loss of Ctx leads to constitutive and uniform RapGAP1 cortical
      localization. We suggest that RapGAP1 functions in the spatial and temporal
      regulation of attachment sites through MyoII assembly via regulation of Rap1
      guanosine triphosphate.

PMID- 18039933
TI  - Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC
      84 domain protein Mps3.
AB  - Positioning of telomeres at the nuclear periphery can have dramatic effects on
      gene expression by establishment of heritable, transcriptionally repressive
      subdomains. However, little is known about the integral membrane proteins that
      mediate telomere tethering at the nuclear envelope. Here, we find a previously
      unrecognized function for the Saccharomyces cerevisiae Sad1-UNC-84 domain protein
      Mps3 in regulating telomere positioning in mitotic cells. Our data demonstrate
      that the nucleoplasmic N-terminal acidic domain of Mps3 is not essential for
      viability. However, this acidic domain is necessary and sufficient for telomere
      tethering during S phase and the silencing of reporter constructs integrated at
      telomeres. We show that this is caused by the role of the Mps3 acidic domain in
      binding and localization of the silent information regulator protein Sir4 to the
      nuclear periphery. Thus, Mps3 functions as an integral membrane anchor for
      telomeres and is a novel nuclear receptor for the Sir4 pathway of telomere
      tethering and gene inactivation.

PMID- 18039934
TI  - Alternative function for the mitochondrial SAM complex in biogenesis of alpha
      helical TOM proteins.
AB  - The mitochondrial outer membrane contains two preprotein translocases: the
      general translocase of outer membrane (TOM) and the beta-barrel-specific sorting
      and assembly machinery (SAM). TOM functions as the central entry gate for nuclear
      encoded proteins. The channel-forming Tom40 is a beta-barrel protein, whereas all
      Tom receptors and small Tom proteins are membrane anchored by a transmembrane
      alpha-helical segment in their N- or C-terminal portion. Synthesis of Tom
      precursors takes place in the cytosol, and their import occurs via preexisting
      TOM complexes. The precursor of Tom40 is then transferred to SAM for membrane
      insertion and assembly. Unexpectedly, we find that the biogenesis of alpha
      helical Tom proteins with a membrane anchor in the C-terminal portion is SAM
      dependent. Each SAM protein is necessary for efficient membrane integration of
      the receptor Tom22, whereas assembly of the small Tom proteins depends on Sam37.
      Thus, the substrate specificity of SAM is not restricted to beta-barrel proteins
      but also includes the majority of alpha-helical Tom proteins.

PMID- 18039935
TI  - NHK-1 phosphorylates BAF to allow karyosome formation in the Drosophila oocyte
      nucleus.
AB  - Accurate chromosome segregation in meiosis requires dynamic changes in chromatin
      organization. In Drosophila melanogaster, upon completion of recombination,
      meiotic chromosomes form a single, compact cluster called the karyosome in an
      enlarged oocyte nucleus. This clustering is also found in humans; however, the
      mechanisms underlying karyosome formation are not understood. In this study, we
      report that phosphorylation of barrier to autointegration factor (BAF) by the
      conserved kinase nucleosomal histone kinase-1 (NHK-1; Drosophila Vrk1) has a
      critical function in karyosome formation. We find that the noncatalytic domain of
      NHK-1 is crucial for its kinase activity toward BAF, a protein that acts as a
      linker between chromatin and the nuclear envelope. A reduction of NHK-1 or
      expression of nonphosphorylatable BAF results in ectopic association of
      chromosomes with the nuclear envelope in oocytes. We propose that BAF
      phosphorylation by NHK-1 disrupts anchorage of chromosomes to the nuclear
      envelope, allowing karyosome formation in oocytes. These data provide the first
      mechanistic insight into how the karyosome forms.

PMID- 18039936
TI  - MCAK facilitates chromosome movement by promoting kinetochore microtubule
      turnover.
AB  - Mitotic centromere-associated kinesin (MCAK)/Kif2C is the most potent microtubule
      (MT)-destabilizing enzyme identified thus far. However, MCAK's function at the
      centromere has remained mechanistically elusive because of interference from
      cytoplasmic MCAK's global regulation of MT dynamics. In this study, we present
      MCAK chimeras and mutants designed to target centromere-associated MCAK for
      mechanistic analysis. Live imaging reveals that depletion of centromere
      associated MCAK considerably decreases the directional coordination between
      sister kinetochores. Sister centromere directional antagonism results in
      decreased movement speed and increased tension. Sister centromeres appear unable
      to detach from kinetochore MTs efficiently in response to directional switching
      cues during oscillatory movement. These effects are reversed by anchoring ectopic
      MCAK to the centromere. We propose that MCAK increases the turnover of
      kinetochore MTs at all centromeres to coordinate directional switching between
      sister centromeres and facilitate smooth translocation. This may contribute to
      error correction during chromosome segregation either directly via slow MT
      turnover or indirectly by mechanical release of MTs during facilitated movement.

PMID- 18039937
TI  - In vivo visualization of type II plasmid segregation: bacterial actin filaments
      pushing plasmids.
AB  - Type II par operons harness polymerization of the dynamically unstable actin-like
      protein ParM to segregate low-copy plasmids in rod-shaped bacteria. In this
      study, we use time-lapse fluorescence microscopy to follow plasmid dynamics and
      ParM assembly in Escherichia coli. Plasmids lacking a par operon undergo confined
      diffusion with a diffusion constant of 5 x 10(-5) microm(2)/s and a confinement
      radius of 0.28 microm. Single par-containing plasmids also move diffusively but
      with a larger diffusion constant (4 x 10(-4) microm(2)/s) and confinement radius
      (0.42 microm). ParM filaments are dynamically unstable in vivo and form spindles
      that link pairs of par-containing plasmids and drive them rapidly (3.1
      microm/min) toward opposite poles of the cell. After reaching the poles, ParM
      filaments rapidly and completely depolymerize. After ParM disassembly, segregated
      plasmids resume diffusive motion, often encountering each other many times and
      undergoing multiple rounds of ParM-dependent segregation in a single cell cycle.
      We propose that in addition to driving segregation, the par operon enables
      plasmids to search space and find sister plasmids more effectively.

PMID- 18039938
TI  - Plasmid segregation: spatial awareness at the molecular level.
AB  - In bacteria, low-copy number plasmids ensure their stable inheritance by
      partition loci (par), which actively distribute plasmid replicates to each side
      of the cell division plane. Using time-lapse fluorescence microscopic tracking of
      segregating plasmid molecules, a new study provides novel insight into the
      workings of the par system from Escherichia coli plasmid R1. Despite its relative
      simplicity, the plasmid partition spindle shares characteristics with the mitotic
      machinery of eukaryotic cells.

PMID- 18039939
TI  - Target of rapamycin and LST8 proteins associate with membranes from the
      endoplasmic reticulum in the unicellular green alga Chlamydomonas reinhardtii.
AB  - The highly conserved target of rapamycin (TOR) kinase is a central controller of
      cell growth in all eukaryotes. TOR exists in two functionally and structurally
      distinct complexes, termed TOR complex 1 (TORC1) and TORC2. LST8 is a TOR
      interacting protein that is present in both TORC1 and TORC2. Here we report the
      identification and characterization of TOR and LST8 in large protein complexes in
      the model photosynthetic green alga Chlamydomonas reinhardtii. We demonstrate
      that Chlamydomonas LST8 is part of a rapamycin-sensitive TOR complex in this
      green alga. Biochemical fractionation and indirect immunofluorescence microscopy
      studies indicate that TOR and LST8 exist in high-molecular-mass complexes that
      associate with microsomal membranes and are particularly abundant in the peri
      basal body region in Chlamydomonas cells. A Saccharomyces cerevisiae
      complementation assay demonstrates that Chlamydomonas LST8 is able to
      functionally and structurally replace endogenous yeast LST8 and allows us to
      propose that binding of LST8 to TOR is essential for cell growth.

PMID- 18039940
TI  - Extracellular vesicles produced by Cryptococcus neoformans contain protein
      components associated with virulence.
AB  - Cryptococcus neoformans produces vesicles containing its major virulence factor,
      the capsular polysaccharide glucuronoxylomannan (GXM). These vesicles cross the
      cell wall to reach the extracellular space, where the polysaccharide is
      supposedly used for capsule growth or delivered into host tissues. In the present
      study, we characterized vesicle morphology and protein composition by a
      combination of techniques including electron microscopy, proteomics, enzymatic
      activity, and serological reactivity. Secretory vesicles in C. neoformans appear
      to be correlated with exosome-like compartments derived from multivesicular
      bodies. Extracellular vesicles manifested various sizes and morphologies,
      including electron-lucid membrane bodies and electron-dense vesicles. Seventy-six
      proteins were identified by proteomic analysis, including several related to
      virulence and protection against oxidative stress. Biochemical tests indicated
      laccase and urease activities in vesicles. In addition, different vesicle
      proteins were recognized by sera from patients with cryptococcosis. These results
      reveal an efficient and general mechanism of secretion of pathogenesis-related
      molecules in C. neoformans, suggesting that extracellular vesicles function as
      "virulence bags" that deliver a concentrated payload of fungal products to host
      effector cells and tissues.

PMID- 18039941
TI  - Vegetative hyphal fusion is not essential for plant infection by Fusarium
      oxysporum.
AB  - Vegetative hyphal fusion (VHF) is a ubiquitous phenomenon in filamentous fungi
      whose biological role is poorly understood. In Neurospora crassa, the mitogen
      activated protein kinase (MAPK) Mak-2 and the WW domain protein So are required
      for efficient VHF. A MAPK orthologous to Mak-2, Fmk1, was previously shown to be
      essential for root penetration and pathogenicity of the vascular wilt fungus
      Fusarium oxysporum. Here we took a genetic approach to test two hypotheses, that
      (i) VHF and plant infection have signaling mechanisms in common and (ii) VHF is
      required for efficient plant infection. F. oxysporum mutants lacking either Fmk1
      or Fso1, an orthologue of N. crassa So, were impaired in the fusion of vegetative
      hyphae and microconidial germ tubes. Deltafmk1 Deltafso1 double mutants exhibited
      a more severe fusion phenotype than either single mutant, indicating that the two
      components function in distinct pathways. Both Deltafso1 and Deltafmk1 strains
      were impaired in the formation of hyphal networks on the root surface, a process
      associated with extensive VHF. The Deltafso1 mutants exhibited slightly reduced
      virulence in tomato fruit infection assays but, in contrast to Deltafmk1 strains,
      were still able to perform functions associated with invasive growth, such as
      secretion of pectinolytic enzymes or penetration of cellophane sheets, and to
      infect tomato plants. Thus, although VHF per se is not essential for plant
      infection, both processes have some signaling components in common, suggesting an
      evolutionary relationship between the underlying cellular mechanisms.

PMID- 18039942
TI  - Binding of the wheat germ lectin to Cryptococcus neoformans suggests an
      association of chitinlike structures with yeast budding and capsular
      glucuronoxylomannan.
AB  - The capsule of Cryptococcus neoformans is a complex structure whose assembly
      requires intermolecular interactions to connect its components into an organized
      structure. In this study, we demonstrated that the wheat germ agglutinin (WGA),
      which binds to sialic acids and beta-1,4-N-acetylglucosamine (GlcNAc) oligomers,
      can also bind to cryptococcal capsular structures. Confocal microscopy
      demonstrated that these structures form round or hooklike projections linking the
      capsule to the cell wall, as well as capsule-associated structures during yeast
      budding. Chemical analysis of capsular extracts by gas chromatography coupled to
      mass spectrometry and high-pH anion-exchange chromatography suggested that the
      molecules recognized by WGA were firmly associated with the cell wall. Enzymatic
      treatment, competition assays, and staining with chemically modified WGA revealed
      that GlcNAc oligomers, but not sialic acids, were the molecules recognized by the
      lectin. Accordingly, treatment of C. neoformans cells with chitinase released
      glucuronoxylomannan (GXM) from the cell surface and reduced the capsule size.
      Chitinase-treated acapsular cells bound soluble GXM in a modified pattern. These
      results indicate an association of chitin-derived structures with GXM and budding
      in C. neoformans, which may represent a new mechanism by which the capsular
      polysaccharide interacts with the cell wall and is rearranged during replication.

PMID- 18039943
TI  - Ras GTPase-activating protein regulation of actin cytoskeleton and hyphal
      polarity in Aspergillus nidulans.
AB  - Aspergillus nidulans gapA1, a mutation leading to compact, fluffy colonies and
      delayed polarity establishment, maps to a gene encoding a Ras GTPase-activating
      protein. Domain organization and phylogenetic analyses strongly indicate that
      GapA regulates one or more "true" Ras proteins. A gapADelta strain is viable.
      gapA colonies are more compact than gapA1 colonies and show reduced conidiation.
      gapADelta strains have abnormal conidiophores, characterized by the absence of
      one of the two layers of sterigmata seen in the wild type. gapA transcript levels
      are very low in conidia but increase during germination and reach their maximum
      at a time coincident with germ tube emergence. Elevated levels persist in hyphae.
      In germinating conidiospores, gapADelta disrupts the normal coupling of isotropic
      growth, polarity establishment, and mitosis, resulting in a highly heterogeneous
      cell population, including malformed germlings and a class of giant cells with no
      germ tubes and a multitude of nuclei. Unlike wild-type conidia, gapADelta conidia
      germinate without a carbon source. Giant multinucleated spores and carbon source
      independent germination have been reported in strains carrying a rasA dominant
      active allele, indicating that GapA downregulates RasA. gapADelta cells show a
      polarity maintenance defect characterized by apical swelling and subapical
      branching. The strongly polarized wild-type F-actin distribution is lost in
      gapADelta cells. As GapA-green fluorescent protein shows cortical localization
      with strong predominance at the hyphal tips, we propose that GapA-mediated
      downregulation of Ras signaling at the plasma membrane of these tips is involved
      in the polarization of the actin cytoskeleton that is required for hyphal growth
      and, possibly, for asexual morphogenesis.

PMID- 18039944
TI  - Iron starvation and culture age activate metacaspases and programmed cell death
      in the marine diatom Thalassiosira pseudonana.
AB  - In the modern ocean, phytoplankton maintain extremely high primary
      production/biomass ratios, indicating that they bloom, die, and are replaced
      weekly. The molecular mechanisms regulating cellular mortality and turnover are
      largely unknown, even though they effectively short-circuit carbon export to the
      deep ocean and channel primary productivity to microbial food webs. Here, we
      present morphological, biochemical, and molecular evidence of caspase-mediated,
      autocatalytic programmed cell death (PCD) in the diatom Thalassiosira pseudonana
      in response to iron starvation. Transmission electron microscopy revealed
      internal degradation of nuclear, chloroplastic, and mitochondrial organelles, all
      while the plasma membranes remained intact. Cellular degradation was concomitant
      with dramatic decreases in photosynthetic efficiency, externalization of
      phosphatidylserine, and significantly elevated caspase-specific activity, with
      the addition of a broad-spectrum caspase inhibitor rescuing cells from death. A
      search of the T. pseudonana genome identified six distinct putative metacaspases
      containing a conserved caspase domain structure. Quantitative reverse
      transcription-PCR and Western blot analysis revealed differential gene and
      protein expression of T. pseudonana metacaspases, some of which correlated with
      physiological stress and caspase activity. Taken together with the recent
      discovery of the metacaspase-mediated viral infection of phytoplankton (K. D.
      Bidle, L. Haramaty, J. Barcelos-Ramos, and P. G. Falkowski, Proc. Natl. Acad.
      Sci. USA 104:6049-6054, 2007), our findings reveal a key role for metacaspases in
      the turnover of phytoplankton biomass in the oceans. Furthermore, given that Fe
      is required for photosynthetic electron transfer and is chronically limiting in a
      variety of oceanic systems, including high-nutrient low-chlorophyll regions, our
      findings provide a potential ecological context for PCD in these unicellular
      photoautotrophs.

PMID- 18039945
TI  - Kelch repeat protein Clakel2p and calcium signaling control appressorium
      development in Colletotrichum lagenarium.
AB  - Kelch repeat proteins are important mediators of fundamental cellular functions
      and are found in diverse organisms. However, the roles of these proteins in
      filamentous fungi have not been characterized. We isolated a kelch repeat
      encoding gene of Colletotrichum lagenarium ClaKEL2, a Schizosaccharomyces pombe
      tea1 homologue. Analysis of the clakel2 mutant indicated that ClaKEL2 was
      required for the establishment of cellular polarity essential for proper
      morphogenesis of appressoria and that there is a plant signal-specific bypass
      pathway for appressorium development which circumvents ClaKEL2 function. Clakel2p
      was localized in the polarized region of growing hyphae and germ tubes, and the
      localization was disturbed by a microtubule assembly blocker. The clakel2 mutants
      formed abnormal appressoria, and those appressoria were defective in penetration
      hypha development into cellulose membranes, an artificial model substrate for
      fungal infection. Surprisingly, the clakel2 mutants formed normal appressoria on
      the host plant and retained penetration ability. Normal appressorium formation on
      the artificial substrate by the clakel2 mutants was restored when cells were
      incubated in the presence of CaCl(2) or exudates from cucumber cotyledon.
      Furthermore, calcium channel modulators inhibited restoration of normal
      appressorium formation. These results suggest that there could be a bypass
      pathway that transduces a plant-derived signal for appressorium development
      independent of ClaKEL2 and that a calcium signal is involved in this transduction
      pathway.

PMID- 18039946
TI  - Further delineation of cardio-facio-cutaneous syndrome: clinical features of 38
      individuals with proven mutations.
AB  - BACKGROUND: Cardio-facio-cutaneous syndrome (CFC) is a multiple congenital
      anomaly/mental retardation syndrome named because of a characteristic facies,
      cardiac anomalies, and ectodermal abnormalities. While considerable literature
      describes the main features, few studies have documented the frequencies of less
      common features allowing a greater appreciation of the full phenotype. METHODS:
      We have analysed clinical data on 38 individuals with CFC and a confirmed
      mutation in one of the genes known to cause the condition. We provide data on
      well-established features, and those that are less often described. RESULTS:
      Polyhydramnios (77%) and prematurity (49%) were common perinatal issues. 71% of
      individuals had a cardiac anomaly, the most common being pulmonary valve stenosis
      (42%), hypertrophic cardiomyopathy (39%), and atrial septal defect (28%). Hair
      anomalies were also typical: 92% had curly hair, 84% sparse hair, and 86% absent
      or sparse eyebrows. The most frequent cutaneous features were keratosis pilaris
      (73%), hyperkeratosis (61%) and nevi (76%). Significant and long lived
      gastrointestinal dysmotility (71%), seizures (49%), optic nerve hypoplasia (30%)
      and renal anomalies, chiefly hydronephrosis (20%), were among the less well known
      issues reported. CONCLUSION: This study reports a broad range of clinical issues
      in a large cohort of individuals with molecular confirmation of CFC.

PMID- 18039947
TI  - Severe neonatal manifestations of Costello syndrome.
AB  - BACKGROUND: Costello syndrome (CS) is due to mutations in HRAS, with the most
      common mutation being c.34G>A (p.G12S), found in most patients in all the
      published series. A small number of less common mutations have been reported.
      POPULATION STUDIED: HRAS mutation analysis has been undertaken in 74
      predominantly British patients with a possible diagnosis of CS. A HRAS mutation
      was found in 27 patients, 15 of whom have been previously reported. PHENOTYPE
      ANALYSIS: Four cases had an unusually severe phenotype, associated in three cases
      with two unusual mutations, c.35G>A, p.G12D in two cases and c.34G>T, p.G12C in
      the other. Hypoglycaemia, renal abnormalities, severe early cardiomyopathy,
      congenital lung and airway abnormalities, pleural and pericardial effusion,
      chylous ascites and pulmonary lymphangectasia are confirmed as part of the
      clinical spectrum seen in CS. A lung pathology resembling alveolar capillary
      dysplasia is reported in one case. CONCLUSION: These cases illustrate that the
      diagnosis of CS may be difficult in the newborn period, and should be considered
      in the differential diagnosis of the sick newborn infant with multisystem
      disease. Study of more cases will be required to establish if there is a definite
      association between severe disease and less common mutations.

PMID- 18039948
TI  - Genomic imbalances associated with mullerian aplasia.
AB  - BACKGROUND: Aplasia of the mullerian ducts leads to absence of the uterine
      corpus, uterine cervix, and upper (superior) vagina. Patients with mullerian
      aplasia (MA) often exhibit additional clinical features such as renal, vertebral
      and cardiac defects. A number of different syndromes have been associated with
      MA, and in most cases its aetiology remains poorly understood. OBJECTIVE AND
      METHODS: 14 syndromic patients with MA and 46,XX G-banded karyotype were screened
      for DNA copy number changes by approximately 1 Mb whole genome bacterial
      artificial chromosome (BAC) array based comparative genomic hybridisation (CGH).
      The detected alterations were validated by an independent method and further
      mapped by high resolution oligo-arrays. RESULTS: Submicroscopic genomic
      imbalances affecting the 1q21.1, 17q12, 22q11.21, and Xq21.31 chromosome regions
      were detected in four probands. Presence of the alterations in the normal mother
      of one patient suggests incomplete penetrance and/or variable expressivity.
      CONCLUSION: 4 of the 14 patients (29%) were found to have cryptic genomic
      alterations. The imbalances on 22q11.21 support recent findings by us and others
      that alterations in this chromosome region may result in impairment of mullerian
      duct development. The remaining imbalances indicate involvement of previously
      unknown chromosome regions in MA, and point specifically to LHX1 and KLHL4 as
      candidate genes.

PMID- 18039949
TI  - Amelioration of epidermal hyperplasia by TNF inhibition is associated with
      reduced Th17 responses.
AB  - Biological agents have dramatically improved treatment options for patients with
      severe psoriasis. Etanercept (tumor necrosis factor [TNF] receptor-immunoglobulin
      fusion protein) is an effective treatment for many psoriasis patients, and
      blockade of TNF is considered to be its primary action. However, in this clinical
      trial, we show that etanercept has early inhibitory effects on a newly
      appreciated type of T cells: T helper type 17 (Th17) cells. Etanercept reduced
      the inflammatory dendritic cell products that drive Th17 cell proliferation
      (interleukin [IL] 23), as well as Th17 cell products and downstream effector
      molecules (IL-17, IL-22, CC chemokine ligand 20, and beta-defensin 4). In
      contrast, Th1 cellular products and effector molecules (interferon gamma,
      lymphotoxin alpha, and myxovirus resistance 1) were reduced late in disease
      resolution. This study suggests a role for Th17 in addition to Th1 cells in the
      pathogenesis of psoriasis. Th17 cells may be particularly important in driving
      epidermal activation in psoriatic plaques, whereas Th1 cells must also be
      eliminated for final disease resolution.

PMID- 18039950
TI  - B cell intrinsic TLR signals amplify but are not required for humoral immunity.
AB  - Although innate signals driven by Toll-like receptors (TLRs) play a crucial role
      in T-dependent immune responses and serological memory, the precise cellular and
      time-dependent requirements for such signals remain poorly defined. To directly
      address the role for B cell-intrinsic TLR signals in these events, we compared
      the TLR response profile of germinal center (GC) versus naive mature B cell
      subsets. TLR responsiveness was markedly up-regulated during the GC reaction, and
      this change correlated with altered expression of the key adaptors MyD88, Mal,
      and IRAK-M. To assess the role for B cell-intrinsic signals in vivo, we
      transferred MyD88 wild-type or knockout B cells into B cell-deficient microMT
      mice and immunized recipient animals with 4-hydroxy-3-nitrophenylacetyl (NP)
      chicken gamma globulin. All recipients exhibited similar increases in NP-specific
      antibody titers during primary, secondary, and long-term memory responses. The
      addition of lipopolysaccharide to the immunogen enhanced B cell-intrinsic, MyD88
      dependent NP-specific immunoglobulin (Ig)M production, whereas NP-specific IgG
      increased independently of TLR signaling in B cells. Our data demonstrate that B
      cell-intrinsic TLR responses are up-regulated during the GC reaction, and that
      this change significantly promotes antigen-specific IgM production in association
      with TLR ligands. However, B cell-intrinsic TLR signals are not required for
      antibody production or maintenance.

PMID- 18039951
TI  - JAM-A regulates permeability and inflammation in the intestine in vivo.
AB  - Recent evidence has linked intestinal permeability to mucosal inflammation, but
      molecular studies are lacking. Candidate regulatory molecules localized within
      the tight junction (TJ) include Junctional Adhesion Molecule (JAM-A), which has
      been implicated in the regulation of barrier function and leukocyte migration.
      Thus, we analyzed the intestinal mucosa of JAM-A-deficient (JAM-A(-/-)) mice for
      evidence of enhanced permeability and inflammation. Colonic mucosa from JAM-A(-/
      ) mice had normal epithelial architecture but increased polymorphonuclear
      leukocyte infiltration and large lymphoid aggregates not seen in wild-type
      controls. Barrier function experiments revealed increased mucosal permeability,
      as indicated by enhanced dextran flux, and decreased transepithelial electrical
      resistance in JAM-A(-/-) mice. The in vivo observations were epithelial specific,
      because monolayers of JAM-A(-/-) epithelial cells also demonstrated increased
      permeability. Analyses of other TJ components revealed increased expression of
      claudin-10 and -15 in the colonic mucosa of JAM-A(-/-) mice and in JAM-A small
      interfering RNA-treated epithelial cells. Given the observed increase in colonic
      inflammation and permeability, we assessed the susceptibility of JAM-A(-/-) mice
      to the induction of colitis with dextran sulfate sodium (DSS). Although DSS
      treated JAM-A(-/-) animals had increased clinical disease compared with controls,
      colonic mucosa showed less injury and increased epithelial proliferation. These
      findings demonstrate a complex role of JAM-A in intestinal homeostasis by
      regulating epithelial permeability, inflammation, and proliferation.

PMID- 18039952
TI  - Yellow fever and Max Theiler: the only Nobel Prize for a virus vaccine.
AB  - In 1951, Max Theiler of the Rockefeller Foundation received the Nobel Prize in
      Physiology or Medicine for his discovery of an effective vaccine against yellow
      fever--a discovery first reported in the JEM 70 years ago. This was the first,
      and so far the only, Nobel Prize given for the development of a virus vaccine.
      Recently released Nobel archives now reveal how the advances in the yellow fever
      vaccine field were evaluated more than 50 years ago, and how this led to a prize
      for Max Theiler.

PMID- 18039953
TI  - Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances
      sensitivity to chemotherapy.
AB  - Drug resistance remains a critical problem in the treatment of patients with
      multiple myeloma. Recent studies have determined that Notch signaling plays a
      major role in bone marrow (BM) stroma-mediated protection of myeloma cells from
      de novo drug-induced apoptosis. Here, we investigated whether pharmacologic
      inhibition of Notch signaling could affect the viability of myeloma cells and
      their sensitivity to chemotherapy. Treatment with a gamma-secretase inhibitor
      (GSI) alone induced apoptosis of myeloma cells via specific inhibition of Notch
      signaling. At concentrations toxic for myeloma cell lines and primary myeloma
      cells, GSI did not affect normal BM or peripheral blood mononuclear cells.
      Treatment with GSI prevented BM stroma-mediated protection of myeloma cells from
      drug-induced apoptosis. The cytotoxic effect of GSI was mediated via Hes-1 and up
      regulation of the proapoptotic protein Noxa. In vivo experiments using xenograft
      and SCID-hu models of multiple myeloma demonstrated substantial antitumor effect
      of GSI. In addition, GSI significantly improved the cytotoxicity of the
      chemotherapeutic drugs doxorubicin and melphalan. Thus, this study demonstrates
      that inhibition of Notch signaling prevents BM-mediated drug resistance and
      sensitizes myeloma cells to chemotherapy. This may represent a promising approach
      for therapeutic intervention in multiple myeloma.

PMID- 18039954
TI  - Valganciclovir prevents cytomegalovirus reactivation in patients receiving
      alemtuzumab-based therapy.
AB  - Alemtuzumab is an immunosuppressive antibody that depletes normal T cells and B
      cells. Prophylaxis for herpes virus and Pneumocystis carinii is standard with
      this agent. Approximately 20% to 25% of patients will experience cytomegalovirus
      (CMV) reactivation. We conducted a randomized trial wherein patients being
      treated with an alemtuzumab-containing regimen received prophylaxis with either
      valaciclovir 500 mg orally daily or valganciclovir 450 mg orally twice daily. The
      study design planned to enroll 128 patients, but stopping rules for early
      termination were met. Forty patients were evaluable. Median age was 58 years
      (range, 25-83 years); median number of prior therapies was 2 (range, 0-10).
      Diagnoses included chronic lymphocytic leukemia (29), T-cell prolymphocytic
      leukemia (3), hairy cell leukemia (1), adult T-cell leukemia/lymphoma (ATLL) (1),
      marginal zone leukemia (1), large granular lymphocyte leukemia (2), acute
      lymphoblastic leukemia (1), and T-cell lymphoma (2). Patients received various
      alemtuzumab-containing regimens, including single agent (5) or combined with:
      rituximab (2), pentostatin (6), fludarabine, cyclophosphamide, and rituximab
      (23), or fractionated cyclophosphamide, vincristine, adriamycin, and
      dexamethasone (hyper-CVAD) (4). Seven of 20 patients enrolled on the valaciclovir
      arm experienced CMV reactivation. None of the 20 patients randomized to
      valganciclovir experienced CMV reactivation (P = .004). In conclusion, this agent
      was highly effective for prophylaxis of CMV reactivation in patients receiving
      alemtuzumab. This trial was registered at www.ClinicalTrials.gov as #NCT00562770.

PMID- 18039955
TI  - Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early
      T-cell development.
AB  - Although several cytokines have been demonstrated to be critical regulators of
      development of multiple blood cell lineages, it remains disputed to what degree
      they act through instructive or permissive mechanisms. Signaling through the FMS
      like tyrosine kinase 3 (FLT3) receptor and the hematopoietin IL-7 receptor alpha
      (IL-7Ralpha) has been demonstrated to be of critical importance for sustained
      thymopoiesis. Signaling triggered by IL-7 and thymic stromal lymphopoietin (TSLP)
      is dependent on IL-7Ralpha, and both ligands have been implicated in T-cell
      development. However, we demonstrate that, whereas thymopoiesis is abolished in
      adult mice doubly deficient in IL-7 and FLT3 ligand (FLT3L), TSLP does not play a
      key role in IL-7-independent or FLT3L-independent T lymphopoiesis. Furthermore,
      whereas previous studies implicated that the role of other cytokine tyrosine
      kinase receptors in T lymphopoiesis might not involve permissive actions, we
      demonstrate that ectopic expression of BCL2 is sufficient not only to partially
      correct the T-cell phenotype of Flt3l(-/-) mice but also to rescue the virtually
      complete loss of all discernable stages of early T lymphopoiesis in Flt3l(-/
      )Il7r(-/-) mice. These findings implicate a permissive role of cytokine receptors
      of the hematopoietin and tyrosine kinase families in early T lymphopoiesis.

PMID- 18039956
TI  - NSOM/QD-based nanoscale immunofluorescence imaging of antigen-specific T-cell
      receptor responses during an in vivo clonal Vgamma2Vdelta2 T-cell expansion.
AB  - Nanoscale imaging of an in vivo antigen-specific T-cell immune response has not
      been reported. Here, the combined near-field scanning optical microscopy- and
      fluorescent quantum dot-based nanotechnology was used to perform
      immunofluorescence imaging of antigen-specific T-cell receptor (TCR) response in
      an in vivo model of clonal T-cell expansion. The near-field scanning optical
      microscopy/quantum dot system provided a best-optical-resolution (<50 nm) nano
      scale imaging of Vgamma2Vdelta2 TCR on the membrane of nonstimulated
      Vgamma2Vdelta2 T cells. Before Ag-induced clonal expansion, these nonstimulating
      Vgamma2Vdelta2 TCRs appeared to be distributed differently from their alphabeta
      TCR counterparts on the cell surface. Surprisingly, Vgamma2Vdelta2 TCR
      nanoclusters not only were formed but also sustained on the membrane during an in
      vivo clonal expansion of Vgamma2Vdelta2 T cells after phosphoantigen treatment or
      phosphoantigen plus mycobacterial infection. The TCR nanoclusters could array to
      form nanodomains or microdomains on the membrane of clonally expanded
      Vgamma2Vdelta2 T cells. Interestingly, expanded Vgamma2Vdelta2 T cells bearing
      TCR nanoclusters or nanodomains were able to rerecognize phosphoantigen and to
      exert better effector function. These studies provided nanoscale insight into the
      in vivo T-cell immune response.

PMID- 18039957
TI  - Early postinduction intensification therapy improves survival for children and
      adolescents with high-risk acute lymphoblastic leukemia: a report from the
      Children's Oncology Group.
AB  - Longer and more intensive postinduction intensification (PII) improved the
      outcome of children and adolescents with "higher risk" acute lymphoblastic
      leukemia (ALL) and a slow marrow response to induction therapy. In the Children's
      Cancer Group study (CCG-1961), we tested longer versus more intensive PII, using
      a 2 x 2 factorial design for children with higher risk ALL and a rapid marrow
      response to induction therapy. Between November 1996 and May 2002, 2078 children
      and adolescents with newly diagnosed ALL (1 to 9 years old with white blood count
      50 000/mm3 or more, or 10 years of age or older with any white blood count) were
      enrolled. After induction, 1299 patients with marrow blasts less than or equal to
      25% on day 7 of induction (rapid early responders) were randomized to standard or
      longer duration (n = 651 + 648) and standard or increased intensity (n = 649 +
      650) PII. Stronger intensity PII improved event-free survival (81% vs 72%, P <
      .001) and survival (89% vs 83%, P = .003) at 5 years. Differences were most
      apparent after 2 years from diagnosis. Longer duration PII provided no benefit.
      Stronger intensity but not prolonged duration PII improved outcome for patients
      with higher-risk ALL. This study is registered at http://clinicaltrials.gov as
      NCT00002812.

PMID- 18039958
TI  - Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2,3-difluorophenyl)-2
      oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5
      b]pyridin-1-yl)piperidine-1-carboxamide], a potent and orally active calcitonin
      gene-related peptide receptor antagonist for the treatment of migraine.
AB  - Calcitonin gene-related peptide (CGRP) is a potent neuropeptide that plays a key
      role in the pathophysiology of migraine headache. CGRP levels in the cranial
      circulation are increased during a migraine attack, and CGRP itself has been
      shown to trigger migraine-like headache. The correlation between CGRP release and
      migraine headache points to the potential utility of CGRP receptor antagonists as
      novel therapeutics in the treatment of migraine. Indeed, clinical proof-of
      concept in the acute treatment of migraine was demonstrated with an intravenous
      formulation of the CGRP receptor antagonist BIBN4096BS (olcegepant). Here we
      report on the pharmacological characterization of the first orally bioavailable
      CGRP receptor antagonist in clinical development, MK-0974 [N-[(3R,6S)-6-(2,3
      difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro
      1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide]. In vitro, MK-0974 is a
      potent antagonist of the human (K(i) = 0.77 nM) and rhesus (K(i) = 1.2 nM) CGRP
      receptors but displays >1500-fold lower affinity for the canine and rat receptors
      as determined via (125)I-human CGRP competition binding assays. A rhesus
      pharmacodynamic assay measuring capsaicin-induced changes in forearm dermal blood
      flow via laser Doppler imaging was utilized to determine the in vivo activity of
      CGRP receptor antagonism. MK-0974 produced a concentration-dependent inhibition
      of dermal vasodilation, generated by capsaicin-induced release of endogenous
      CGRP, with plasma concentrations of 127 and 994 nM required to block 50 and 90%
      of the blood flow increase, respectively. In conclusion, MK-0974 is a highly
      potent, selective, and orally bioavailable CGRP receptor antagonist, which may be
      valuable in the acute treatment of migraine.

PMID- 18039959
TI  - Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist,
      prevents microparticle-induced vascular hyporeactivity through the regulation of
      proinflammatory proteins.
AB  - Microparticles are plasma membrane vesicles with procoagulant and proinflammatory
      properties. We recently demonstrated that microparticles induce vascular
      hyporeactivity and evoke up-regulation of proinflammatory protein expression.
      This study dissected the effect of either in vitro treatment or short-term oral
      administration of the peroxisome proliferator-activated receptor-gamma
      (PPARgamma) agonist, rosiglitazone, on microparticle-induced vascular
      hyporeactivity of mouse vessels. Microparticles were produced from T cells by
      actinomycin D treatment. The effects of rosiglitazone on mouse aortic rings
      incubated with microparticles were investigated. Aortae treated in vitro with
      rosiglitazone or aortae taken from mice treated by oral administration of the
      same agonist completely prevented microparticle-induced vascular hyporeactivity
      in response to U46619 [9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin
      F(2alpha)). These effects of rosiglitazone occurred independently of the presence
      of endothelium without modifications in blood parameters. The mechanisms involved
      abrogation of nitric oxide (NO) and prostacyclin overproduction linked to up
      regulation of inducible NO-synthase and cyclooxygenase 2 elicited by
      microparticles. In addition, rosiglitazone treatment reduced the ability of
      microparticles to evoke increases in interleukin (IL)-6, IL-8, and nuclear factor
      (NF)-kappaB transcription, and NF-kappaB expression and activation. These results
      suggest that rosiglitazone, via PPARgamma activation, counteracts vascular
      dysfunction associated with increased release of proinflammatory proteins
      elicited by microparticles. They underscore therapeutic perspective for
      rosiglitazone in vascular diseases involving enhanced participation of
      microparticles.

PMID- 18039960
TI  - Orazipone inhibits activation of inflammatory transcription factors nuclear
      factor-kappa B and signal transducer and activator of transcription 1 and
      decreases inducible nitric-oxide synthase expression and nitric oxide production
      in response to inflammatory stimuli.
AB  - Orazipone [OR-1384; 3-[4-(methylsulfonyl)benzylidene]pentane-2,4-dione] is a
      novel sulfhydryl-modulating compound that has anti-inflammatory properties in
      experimental models of asthma and inflammatory bowel disease. In inflammation,
      inducible nitricoxide synthase (iNOS) generates NO, which modulates the immune
      response. Compounds that inhibit iNOS expression or iNOS activity possess anti
      inflammatory effects. In the present study, we examined the effects of orazipone
      and its derivative OR-1958 [3-[3-chlorine-4-(methylsulfonyl)benzylidene]pentane
      2,4-dione] on iNOS expression and NO production in J774 macrophages stimulated by
      bacterial lipopolysaccharide (LPS) and in human alveolar epithelial cells
      activated by proinflammatory cytokines. Protein expression and nuclear
      translocation of transcription factors were measured by Western blot. iNOS mRNA
      expression was determined by quantitative reverse transcription-polymerase chain
      reaction and iNOS mRNA stability by actinomycin D assay. iNOS promoter activity
      was studied in a cell line expressing luciferase under the control of iNOS
      promoter. Orazipone and its derivative OR-1958 but not its nonthiol-modulating
      analog inhibited iNOS expression and NO production in a concentration-dependent
      manner. Orazipone decreased LPS-induced iNOS mRNA expression, but the decay of
      iNOS mRNA was not affected. Orazipone extensively prevented LPS-induced
      activation of nuclear factor kappaB (NF-kappaB) and signal transducer and
      activator of transcription (STAT) 1, which are important transcription factors
      for iNOS. In agreement, human iNOS promoter activity was inhibited by orazipone.
      In conclusion, orazipone decreased activation of inflammatory transcription
      factors NF-kappaB and STAT1, and expression of iNOS in cells exposed to
      inflammatory stimuli. The thiolmodulating property seems to be critical in
      mediating the antiinflammatory effects of orazipone.

PMID- 18039967
TI  - Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches,
      heart and sensory vibrissae in mice.
AB  - The zinc-finger transcriptional repressor Blimp1 (Prdm1) controls gene expression
      patterns during differentiation of B lymphocytes and regulates epigenetic changes
      required for specification of primordial germ cells. Blimp1 is dynamically
      expressed at diverse tissue sites in the developing mouse embryo, but its
      functional role remains unknown because Blimp1 mutant embryos arrest at E10.5 due
      to placental insufficiency. To explore Blimp1 activities at later stages in the
      embryo proper, here we used a conditional inactivation strategy. A Blimp1-Cre
      transgenic strain was also exploited to generate a fate map of Blimp1-expressing
      cells. Blimp1 plays essential roles in multipotent progenitor cell populations in
      the posterior forelimb, caudal pharyngeal arches, secondary heart field and
      sensory vibrissae and maintains key signalling centres at these diverse tissues
      sites. Interestingly, embryos carrying a hypomorphic Blimp1gfp reporter allele
      survive to late gestation and exhibit similar, but less severe developmental
      abnormalities, whereas transheterozygous Blimp1(gfp/-) embryos with further
      reduced expression levels, display exacerbated defects. Collectively, the present
      experiments demonstrate that Blimp1 requirements in diverse cell types are
      exquisitely dose dependent.

PMID- 18039968
TI  - Ttrap is an essential modulator of Smad3-dependent Nodal signaling during
      zebrafish gastrulation and left-right axis determination.
AB  - During vertebrate development, signaling by the TGFbeta ligand Nodal is critical
      for mesoderm formation, correct positioning of the anterior-posterior axis,
      normal anterior and midline patterning, and left-right asymmetric development of
      the heart and viscera. Stimulation of Alk4/EGF-CFC receptor complexes by Nodal
      activates Smad2/3, leading to left-sided expression of target genes that promote
      asymmetric placement of certain internal organs. We identified Ttrap as a novel
      Alk4- and Smad3-interacting protein that controls gastrulation movements and left
      right axis determination in zebrafish. Morpholino-mediated Ttrap knockdown
      increases Smad3 activity, leading to ectopic expression of snail1a and apparent
      repression of e-cadherin, thereby perturbing cell movements during convergent
      extension, epiboly and node formation. Thus, although the role of Smad proteins
      in mediating Nodal signaling is well-documented, the functional characterization
      of Ttrap provides insight into a novel Smad partner that plays an essential role
      in the fine-tuning of this signal transduction cascade.

PMID- 18039969
TI  - Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and
      sensory hair cells during inner ear development.
AB  - Temporal and spatial coordination of multiple cell fate decisions is essential
      for proper organogenesis. Here, we define gene interactions that transform the
      neurogenic epithelium of the developing inner ear into specialized mechanosensory
      receptors. By Cre-loxP fate mapping, we show that vestibular sensory hair cells
      derive from a previously neurogenic region of the inner ear. The related bHLH
      genes Ngn1 (Neurog1) and Math1 (Atoh1) are required, respectively, for neural and
      sensory epithelial development in this system. Our analysis of mouse mutants
      indicates that a mutual antagonism between Ngn1 and Math1 regulates the
      transition from neurogenesis to sensory cell production during ear development.
      Furthermore, we provide evidence that the transition to sensory cell production
      involves distinct autoregulatory behaviors of Ngn1 (negative) and Math1
      (positive). We propose that Ngn1, as well as promoting neurogenesis, maintains an
      uncommitted progenitor cell population through Notch-mediated lateral inhibition,
      and Math1 irreversibly commits these progenitors to a hair-cell fate.

PMID- 18039970
TI  - Spermatocyte cytokinesis requires rapid membrane addition mediated by ARF6 on
      central spindle recycling endosomes.
AB  - The dramatic cell shape changes during cytokinesis require the interplay between
      microtubules and the actomyosin contractile ring, and addition of membrane to the
      plasma membrane. Numerous membrane-trafficking components localize to the central
      spindle during cytokinesis, but it is still unclear how this machinery is
      targeted there and how membrane trafficking is coordinated with cleavage furrow
      ingression. Here we use an arf6 null mutant to show that the endosomal GTPase
      ARF6 is required for cytokinesis in Drosophila spermatocytes. ARF6 is enriched on
      recycling endosomes at the central spindle, but it is required neither for
      central spindle nor actomyosin contractile ring assembly, nor for targeting of
      recycling endosomes to the central spindle. However, in arf6 mutants the cleavage
      furrow regresses because of a failure in rapid membrane addition to the plasma
      membrane. We propose that ARF6 promotes rapid recycling of endosomal membrane
      stores during cytokinesis, which is critical for rapid cleavage furrow
      ingression.

PMID- 18039972
TI  - The transmembrane protein Perdido interacts with Grip and integrins to mediate
      myotube projection and attachment in the Drosophila embryo.
AB  - The molecular mechanisms underlying muscle guidance and formation of myotendinous
      junctions are poorly understood both in vertebrates and in Drosophila. We have
      identified a novel gene that is essential for Drosophila embryonic muscles to
      form proper projections and stable attachments to epidermal tendon cells. Loss-of
      function of this gene - which we named perdido (perd)-results in rounded,
      unattached muscles. perd is expressed prior to myoblast fusion in a subset of
      muscle founder cells, and it encodes a conserved single-pass transmembrane cell
      adhesion protein that contains laminin globular extracellular domains and a small
      intracellular domain with a C-terminal PDZ-binding consensus sequence.
      Biochemical experiments revealed that the Perd intracellular domain interacts
      directly with one of the PDZ domains of the Glutamate receptor interacting
      protein (Grip), another factor required for formation of proper muscle
      projections. In addition, Perd is necessary to localize Grip to the plasma
      membrane of developing myofibers. Using a newly developed, whole-embryo RNA
      interference assay to analyze genetic interactions, perd was shown to interact
      not only with Grip but also with multiple edematous wings, which encodes one
      subunit of the alpha PS1-beta PS integrin expressed in tendon cells. These
      experiments uncovered a previously unrecognized role for the alpha PS1-beta PS
      integrin in the formation of muscle projections during early stages of
      myotendinous junction development. We propose that Perd regulates projection of
      myotube processes toward and subsequent differentiation of the myotendinous
      junction by priming formation of a protein complex through its intracellular
      interaction with Grip and its transient engagement with the tendon cell-expressed
      laminin-binding alpha PS1-beta PS integrin.

PMID- 18039971
TI  - Obligatory participation of macrophages in an angiopoietin 2-mediated cell death
      switch.
AB  - Macrophages have a critical function in the recognition and engulfment of dead
      cells. In some settings, macrophages also actively signal programmed cell death.
      Here we show that during developmentally scheduled vascular regression, resident
      macrophages are an obligatory participant in a signaling switch that favors death
      over survival. This switch occurs when the signaling ligand angiopoietin 2 has
      the dual effect of suppressing survival signaling in vascular endothelial cells
      (VECs) and stimulating Wnt ligand production by macrophages. In response to the
      Wnt ligand, VECs enter the cell cycle and in the absence of survival signals, die
      from G1 phase of the cell cycle. We propose that this mechanism represents an
      adaptation to ensure that the macrophage and its disposal capability are on hand
      when cell death occurs.

PMID- 18039973
TI  - Neuronal calcium sensor-1 modulation of optimal calcium level for neurite
      outgrowth.
AB  - Neurite extension and branching are affected by activity-dependent modulation of
      intracellular Ca2+, such that an optimal window of [Ca2+] is required for
      outgrowth. Our understanding of the molecular mechanisms regulating this optimal
      [Ca2+]i remains unclear. Taking advantage of the large growth cone size of
      cultured primary neurons from pond snail Lymnaea stagnalis combined with dsRNA
      knockdown, we show that neuronal calcium sensor-1 (NCS-1) regulates neurite
      extension and branching, and activity-dependent Ca2+ signals in growth cones. An
      NCS-1 C-terminal peptide enhances only neurite branching and moderately reduces
      the Ca2+ signal in growth cones compared with dsRNA knockdown. Our findings
      suggest that at least two separate structural domains in NCS-1 independently
      regulate Ca2+ influx and neurite outgrowth, with the C-terminus specifically
      affecting branching. We describe a model in which NCS-1 regulates cytosolic Ca2+
      around the optimal window level to differentially control neurite extension and
      branching.

PMID- 18039974
TI  - Semaphorin and neuropilin co-expression in motoneurons sets axon sensitivity to
      environmental semaphorin sources during motor axon pathfinding.
AB  - Class III semaphorins (SemaIIIs) are intercellular cues secreted by surrounding
      tissues to guide migrating cells and axons in the developing organism. This
      chemotropic activity is crucial for the formation of nerves and vasculature.
      Intriguingly, SemaIIIs are also synthesized by neurons during axon pathfinding,
      but their function as intrinsic cues remains unknown. We have explored the role
      of Sema3A expression in motoneurons during spinal nerve development. Loss- and
      gain-of-function in the neural tube of the chick embryo were undertaken to target
      Sema3A expression in motoneurons while preserving Sema3A sources localized in
      peripheral tissues, known to provide important repulsive information for
      delineating the routes of motor axons towards their ventral or dorsal targets.
      Strikingly, Sema3A overexpression induced defasciculation and exuberant growth of
      motor axon projections into these normally non-permissive territories. Moreover,
      knockdown studies showed that motoneuronal Sema3A is required for correct spinal
      nerve compaction and dorsal motor axon extension. Further analysis of Sema3A gain
      and loss-of-function in ex vivo models revealed that Sema3A in motoneurons sets
      the level of sensitivity of their growth cones to exogenous Sema3A exposure. This
      regulation is associated with post-transcriptional and local control of the
      availability of the Sema3A receptor neuropilin 1 at the growth cone surface.
      Thus, by modulating the strength of Sema3A-mediated environmental repulsive
      constraints, Sema3A in motoneurons enables axons to extend more or less far away
      from these repulsive sources. Such interplay between intrinsic and extrinsic
      Sema3A may represent a fundamental mechanism in the accurate specification of
      axon pathways.

PMID- 18039975
TI  - Kinetics of nucleoside uptake by the basolateral side of the sheep choroid plexus
      epithelium perfused in situ.
AB  - Sheep choroid plexus epithelium expresses equilibrative nucleoside transporters
      (ENT) 1 and 2 and concentrative nucleoside transporter 2 at the transcript level.
      This study aimed to explore the kinetics and functional role of these
      transporters at the basolateral side of the sheep choroid plexus epithelium
      perfused in situ. The cellular uptake of [(3)H]adenosine and [(3)H]uridine was
      insensitive to 1 microm nitrobenzylthioinosine (NBTI), and the uptake of
      [(3)H]adenosine was reduced significantly when 10 microm NBTI was present in low
      Na(+) Ringer solution. This might suggest that ENT2, a transporter sensitive to
      micromolar NBTI, is functionally active at the basolateral side of the choroid
      plexus epithelium while ENT1, a transporter sensitive to nanomolar NBTI, is not
      active. When low-Na(+) Ringer solution was used for the in situ perfusion, the
      Na(+) concentration in the venous effluent decreased to 14 mm; under these
      conditions the maximal uptake (U(max)) of [(3)H]adenosine and [(3)H]uridine did
      not change significantly when compared with the U(max) obtained when Ringer
      solution that contained 145 mm Na(+) was used. Kinetic analysis revealed apparent
      Michaelis-Menten constants (K(m,app)) for cellular uptake of [(3)H]adenosine,
      [(3)H]inosine and [(3)H]thymidine of 1.2 +/- 0.2, 15.7 +/- 2.6 and 3.8 +/- 0.9
      microm, respectively. The HPLC and HPLC-fluorometric analysis of the sheep plasma
      and cerebrospinal fluid revealed nanomolar concentrations of adenosine and
      thymidine and micromolar levels of inosine and nucleobases. Considering the
      estimated K(m,app) values, it appears that under normal conditions inosine is the
      more important nucleoside substrate for uptake by the basolateral membrane of the
      choroid plexus epithelium than other nucleosides.

PMID- 18039976
TI  - Evidence from proprioception of fusimotor coactivation during voluntary
      contractions in humans.
AB  - In experiments on position sense at the elbow joint in the horizontal plane,
      blindfolded subjects were required to match the position of one forearm
      (reference) by placement of their other arm (indicator). Position errors were
      measured after conditioning elbow muscles of the reference arm with an isometric
      contraction while the arm was held either flexed or extended. The difference in
      errors after the two forms of conditioning was large when the conditioned muscles
      remained relaxed during the matching process and it became less when elbow
      muscles were required to lift a load during the match (10 and 25% of maximal
      voluntary contraction, respectively). Errors from muscle conditioning were
      attributed to signals arising in muscle spindles and were hypothesized to result
      from the thixotropic property of passive intrafusal fibres. Active muscle does
      not exhibit thixotropy. It is proposed that during a voluntary contraction the
      errors after conditioning are less, because the spindles become coactivated
      through the fusimotor system. The distribution of errors is therefore seen to be
      a reflection of fusimotor recruitment thresholds. For elbow flexors most, but not
      all, fusimotor fibres appear to be recruited by 10% of a maximal contraction.

PMID- 18039977
TI  - Livin' on the edge: imaging dendritic spine turnover in the peri-infarct zone
      during ischemic stroke and recovery.
AB  - The spontaneous recovery of sensory, motor, and cognitive functions after stroke
      is thought to be mediated primarily through the reorganization and rewiring of
      surviving brain circuits. Given that dendritic spine turnover underlies rewiring
      during normal development and plasticity, this process is likely to play a key
      role in mediating functional changes that occur during and after stroke.
      Recently, a new approach has been taken using two-photon microscopy to monitor,
      in real time, the temporal and spatial progression of dendritic plasticity in the
      living animal, both while it is experiencing the initial ischemic episode as well
      as during long-term recovery from stroke damage. Here, we highlight recent
      evidence showing that stroke can trigger extensive changes in the relatively
      hardwired adult brain. For example, when dendrites are challenged by acute
      ischemia, they can disintegrate within minutes of ischemia and rapidly reassemble
      during reperfusion. Over longer time scales, dendrites in the surviving peri
      infarct zone show heightened levels of spine turnover for many weeks after
      stroke, thereby raising the possibility that future stroke therapies may be able
      to facilitate or optimize dendritic rewiring to improve functional recovery.

PMID- 18039978
TI  - More fuel to the debate on the "epidemics of primary aldosteronism".

PMID- 18039979
TI  - Periodontal infection is associated with endothelial dysfunction in healthy
      subjects and hypertensive patients.
AB  - The purpose of this study was to evaluate endothelial function in patients with
      periodontitis. We evaluated forearm blood flow responses to acetylcholine and
      sodium nitroprusside in patients with periodontitis who had no other
      cardiovascular risk factors (32 men; 25+/-3 years of age), in a normal control
      group (20 men; 26+/-3 years of age), and in hypertensive patients with
      periodontitis (28 men and 10 women; 56+/-12 years of age) and without
      periodontitis (control group; 18 men and 6 women; 54+/-13 years of age). Forearm
      blood flow was measured using strain-gauge plethysmography. Circulating levels of
      C-reactive protein and interleukin-6 were significantly higher in the
      periodontitis group than in the control group. Both in healthy and hypertensive
      subjects, forearm blood flow responses to acetylcholine were significantly
      smaller in the periodontitis group than in the control group. Sodium
      nitroprusside-stimulated vasodilation was similar in the 2 groups. Periodontal
      therapy reduced serum concentrations of C-reactive protein and interleukin-6 and
      augmented acetylcholine-induced vasodilation in periodontitis patients with and
      without hypertension. After administration of N(G)-monomethyl-L-arginine, an NO
      synthase inhibitor, forearm blood flow response to acetylcholine was similar
      before and after treatment. These findings suggest that periodontitis is
      associated with endothelial dysfunction in subjects without cardiovascular risk
      factors, as well as hypertensive patients, through a decrease in NO
      bioavailability and that systemic inflammation may be, at least in part, a cause
      of endothelial dysfunction, leading to cardiovascular diseases.

PMID- 18039980
TI  - Daytime and nighttime blood pressure as predictors of death and cause-specific
      cardiovascular events in hypertension.
AB  - Our aim was to assess the prognostic significance of nighttime and daytime
      ambulatory blood pressure and their ratio for mortality and cause-specific
      cardiovascular events in hypertensive patients without major cardiovascular
      disease at baseline. We performed a meta-analysis on individual data of 3468
      patients from 4 prospective studies performed in Europe. Age of the subjects
      averaged 61+/-13 years, 45% were men, 13.7% smoked, 8.4% had diabetes, and 61%
      were under antihypertensive treatment at the time of ambulatory blood pressure
      monitoring. Office, daytime, and nighttime blood pressure averaged 159+/-20/91+/
      12, 143+/-17/87+/-12, and 130+/-18/75+/-12 mm Hg. Total follow-up amounted to 23
      164 patient-years. We used multivariable Cox regression analysis to assess the
      hazard ratios associated with 1 standard deviation higher blood pressure. Daytime
      and nighttime systolic blood pressure predicted all-cause and cardiovascular
      mortality, coronary heart disease, and stroke, independently from office blood
      pressure and confounding variables. When these blood pressures were entered
      simultaneously into the models, nighttime blood pressure predicted all outcomes,
      whereas daytime blood pressure did not add prognostic precision to nighttime
      pressure. Appropriate interaction terms indicated that the results were similar
      in men and women, in younger and older patients, and in treated and untreated
      patients The systolic night-day blood pressure ratio predicted all outcomes,
      which only persisted for all-cause mortality after adjustment for 24-hour blood
      pressure. In conclusion, nighttime blood pressure is in general a better
      predictor of outcome than daytime pressure in hypertensive patients, and the
      night-day blood pressure ratio predicts mortality, even after adjustment for 24
      hour blood pressure.

PMID- 18039981
TI  - A not-so-modest proposal that a "modest" increase in aldosterone causes
      hypertension and more.

PMID- 18039982
TI  - Blood pressure targets after high-risk myocardial infarction: is it time to
      update the guidelines?

PMID- 18039984
TI  - Prediction is difficult, particularly about the future.

PMID- 18039983
TI  - Salt-sensitive blood pressure in mice with increased expression of aldosterone
      synthase.
AB  - To study the effects of modestly increased expression of aldosterone synthase
      (AS), we generated mice (AS(hi/hi)) by replacing the 3' untranslated region of AS
      mRNA with that from a stable mRNA. AS(hi/hi) mice on a normal-salt diet had 1.5
      times the wild-type AS mRNA in adrenals, although their blood pressure and plasma
      aldosterone did not differ from wild-type mice. Changes in dietary salt did not
      affect the blood pressure of wild-type mice, but AS(hi/hi) mice had approximately
      10-mm Hg higher blood pressure on a high-salt diet than on a low-salt diet and
      than wild-type mice on either diet. The AS(hi/hi) mice on a high-salt diet also
      had higher plasma aldosterone, lower plasma potassium, and greater renal
      expression of the alpha subunit of epithelial sodium channel compared with wild
      type mice. The AS(hi/hi) mice on a high-salt diet also had more water intake and
      urine volume and less urine osmolality than wild-type mice. On a low-salt diet,
      AS(hi/hi) mice maintained normal blood pressure with less activation of the renin
      angiotensin-aldosterone system than wild-type mice. The AS(hi/hi) mice also had
      less water intake and urine volume and higher urine osmolality than wild-type
      mice. On a medium high-salt diet, AS(hi/hi) mice were more susceptible than wild
      type mice to infusion of angiotensin II, having a higher blood pressure, greater
      cardiac hypertrophy, and increased oxidative stress. Thus, a modest increase in
      AS expression makes blood pressure more sensitive to salt, suggesting that
      genetically increased AS expression in humans may contribute to hypertension and
      cardiovascular complications in societies with high-salt diets.

PMID- 18039985
TI  - Using cardiovascular age equivalent to close the treatment gap for dyslipidemia.

PMID- 18039986
TI  - Overstating the evidence for lung cancer screening: the International Early Lung
      Cancer Action Program (I-ELCAP) study.
AB  - Last year, the New England Journal of Medicine ran a lead article reporting that
      patients with lung cancer had a 10-year survival approaching 90% if detected by
      screening spiral computed tomography. The publication garnered considerable media
      attention, and some felt that its findings provided a persuasive case for the
      immediate initiation of lung cancer screening. We strongly disagree. In this
      article, we highlight 4 reasons why the publication does not make a persuasive
      case for screening: the study had no control group, it lacked an unbiased outcome
      measure, it did not consider what is already known about this topic from previous
      studies, and it did not address the harms of screening. We conclude with 2
      fundamental principles that physicians should remember when thinking about
      screening: (1) survival is always prolonged by early detection, even when deaths
      are not delayed nor any lives saved, and (2) randomized trials are the only way
      to reliably determine whether screening does more good than harm.

PMID- 18039987
TI  - Patient knowledge of coronary risk profile improves the effectiveness of
      dyslipidemia therapy: the CHECK-UP study: a randomized controlled trial.
AB  - BACKGROUND: Despite increasing evidence that treating dyslipidemia reduces
      cardiovascular events, many patients do not achieve recommended lipid targets.
      METHODS: To determine whether showing physicians and patients the patient's
      calculated coronary risk can improve the effectiveness of treating dyslipidemia
      in a primary care setting, patients were randomized to receive usual care or
      ongoing feedback regarding their calculated coronary risk and the change in this
      risk after lifestyle changes, pharmacotherapy, or both to treat dyslipidemia.
      Outcomes, based on intention-to-treat analysis, included changes in blood lipid
      levels, coronary risk, and the frequency of reaching lipid targets. RESULTS: Two
      hundred thirty primary care physicians enrolled 3,053 patients. After 12 months
      of follow-up, 2,687 patients (88.0%) remained in the study. After adjustment for
      baseline lipid values, significantly greater mean reductions in low-density
      lipoprotein cholesterol levels and the total cholesterol to high-density
      lipoprotein cholesterol ratio were observed in patients receiving risk profiles
      (51.2 mg/dL [to convert to millimoles per liter, multiply by 0.0259] and 1.5,
      respectively) vs usual care (48.0 mg/dL and 1.3, respectively), but the
      differences were small (-3.3 mg/dL; 95% confidence interval [CI], -5.4 to -1.1
      mg/dL; and -0.1; 95% CI, -0.2 to -0.1, respectively). Patients in the risk
      profile group were also more likely to reach lipid targets (odds ratio, 1.26; 95%
      CI, 1.07 to 1.48). A significant dose-response effect was also noted when the
      impact of the risk profile was stronger in those with worse profiles.
      CONCLUSIONS: Discussing coronary risk with the patient is associated with a small
      but measurable improvement in the efficacy of lipid therapy. The value of
      incorporating risk assessment in preventive care should be further evaluated.

PMID- 18039988
TI  - Glycemic index, glycemic load, and cereal fiber intake and risk of type 2
      diabetes in US black women.
AB  - BACKGROUND: Previous studies of carbohydrate quality and risk of type 2 diabetes
      mellitus have yielded inconsistent findings. Because diet is in part culturally
      determined, a study of dietary factors in US black women is of interest. METHODS:
      We used data from the Black Women's Health Study, a prospective cohort study of
      59,000 US black women, to examine the association of glycemic load, glycemic
      index, and cereal fiber with risk of type 2 diabetes. Diet was assessed at
      baseline in 1995 with a modified version of the National Cancer Institute-Block
      food frequency questionnaire. RESULTS: During 8 years of follow-up, there were
      1,938 incident cases of diabetes. Cox proportional hazards models were used to
      estimate incidence rate ratios (IRRs) for quintiles of dietary factors, while
      controlling for lifestyle and dietary factors. Glycemic index was positively
      associated with the risk of diabetes: the IRR for the highest quintile relative
      to the lowest was 1.23 (95% confidence interval [CI], 1.05-1.44). Cereal fiber
      intake was inversely associated with risk of diabetes, with an IRR of 0.82 (95%
      CI, 0.70-0.96) for the highest vs lowest quintiles of intake. Stronger
      associations were seen among women with a body mass index (calculated as weight
      in kilograms divided by height in meters squared) lower than 25: IRRs for the
      highest vs lowest quintile were 1.91 (95% CI, 1.16-3.16) for glycemic index (P
      value for interaction, .12) and 0.41 (95% CI, 0.24-0.72) for cereal fiber intake
      (P value for interaction, .05). CONCLUSION: Increasing cereal fiber in the diet
      may be an effective means of reducing the risk of type 2 diabetes, a disease that
      has reached epidemic proportions in black women.

PMID- 18039989
TI  - Prospective study of dietary carbohydrates, glycemic index, glycemic load, and
      incidence of type 2 diabetes mellitus in middle-aged Chinese women.
AB  - BACKGROUND: Much uncertainty exists about the role of dietary glycemic index and
      glycemic load in the development of type 2 diabetes mellitus, especially in
      populations that traditionally subsist on a diet high in carbohydrates. METHODS:
      We observed a cohort of 64,227 Chinese women with no history of diabetes or other
      chronic disease at baseline for 4.6 years. In-person interviews were conducted to
      collect data on dietary habits, physical activity, and other relevant information
      using a validated questionnaire. Incident diabetes cases were identified via in
      person follow-up. Associations between dietary carbohydrate intake, glycemic
      index, and glycemic load and diabetes incidence were evaluated using
      multivariable Cox proportional hazards models. RESULTS: We identified 1,608
      incident cases of type 2 diabetes mellitus in 297,755 person-years of follow-up.
      Dietary carbohydrate intake and consumption of rice were positively associated
      with risk of developing type 2 diabetes mellitus. The multivariable-adjusted
      estimates of relative risk comparing the highest vs the lowest quintiles of
      intake were 1.28 (95% confidence interval, 1.09-1.50) for carbohydrates and 1.78
      (95% confidence interval, 1.48-2.15) for rice. The relative risk for increasing
      quintiles of intake was 1.00, 1.04, 1.02, 1.09, and 1.21 (95% confidence
      interval, 1.03-1.43) for dietary glycemic index and 1.00, 1.06, 0.97, 1.23, and
      1.34 (95% confidence interval, 1.13-1.58) for dietary glycemic load. CONCLUSION:
      High intake of foods with a high glycemic index and glycemic load, especially
      rice, the main carbohydrate-contributing food in this population, may increase
      the risk of type 2 diabetes mellitus in Chinese women.

PMID- 18039990
TI  - Increasing outpatient fluoroquinolone exposure before tuberculosis diagnosis and
      impact on culture-negative disease.
AB  - BACKGROUND: Fluoroquinolones are widely used to treat routine bacterial
      infections, but they are also potential first-line antituberculosis agents.
      Empirical fluoroquinolone therapy can delay the diagnosis of tuberculosis and
      cause resistance in Mycobacterium tuberculosis. Rates of fluoroquinolone exposure
      before tuberculosis diagnosis and the impact of fluoroquinolones on culture
      negative tuberculosis have not been previously reported. METHODS: All newly
      diagnosed tuberculosis cases reported to the Tennessee Department of Health
      between January 1, 2000, and December 31, 2004, were cross-matched with the
      TennCare (Medicaid) pharmacy database to assess for outpatient fluoroquinolone
      use in the 12 months before tuberculosis diagnosis. RESULTS: Of 1,562
      tuberculosis cases reported, 1,055 occurred in TennCare participants; of these
      1,055 TennCare patients, 507 were enrolled in TennCare more than 300 days during
      the year before tuberculosis diagnosis. Of the 507 patients, 119 (23%) received a
      fluoroquinolone before tuberculosis diagnosis. The proportion of fluoroquinolone
      exposed patients increased from 9% in 2000 to 41% in 2004 (chi(2) test for trend
      P <.001). In multivariate logistic regression analysis, factors associated with
      fluoroquinolone exposure were older age (odds ratio [OR], 1.03 per year; 95%
      confidence interval [CI], 1.02-1.04) and year of diagnosis (OR, 1.64 per 1-year
      increase; 95% CI, 1.39-1.93); human immunodeficiency virus infection tended to be
      associated with increased exposure (OR, 1.94; 95% CI, 0.97-3.90). After
      controlling for age, sex, race, site of disease, human immunodeficiency virus,
      and year of diagnosis, prior fluoroquinolone exposure was not associated with
      culture-negative tuberculosis (OR, 0.81; 95% CI, 0.41-1.60). CONCLUSIONS:
      Fluoroquinolone use before tuberculosis diagnosis increased significantly during
      the study period. However, fluoroquinolone exposure was not associated with an
      increased risk of culture-negative tuberculosis.

PMID- 18039991
TI  - Nonconsented human immunodeficiency virus testing among critically ill patients:
      intensivists' practices and the influence of state laws.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) testing can improve care for many
      critically ill patients, but state laws and institutional policies may impede
      such testing when patients cannot provide consent. METHODS: We electronically
      surveyed all US academic intensivists in 2006 to determine how state laws
      influence intensivists' decisions to perform nonconsented HIV testing and to
      assess intensivists' reliance on surrogate markers of HIV infection when unable
      to obtain HIV tests. We used multivariate logistic regression, clustered by
      state, to identify factors associated with intensivists' decisions to pursue
      nonconsented HIV testing. RESULTS: Of 1,026 responding intensivists, 765 (74.6%)
      had encountered decisionally incapacitated patients for whom HIV testing was
      wanted. Of these intensivists, 168 pursued testing without consent and 476 first
      obtained surrogate consent to testing. Intensivists who believed nonconsented HIV
      testing was ethical (odds ratio, 3.8; 95% confidence interval, 2.2-6.5) and those
      who believed their states allowed nonconsented testing when medically necessary
      (odds ratio, 2.3; 95% confidence interval, 1.6-3.4) were more likely to pursue
      nonconsented HIV tests; actual state laws were unrelated to testing practices. Of
      the intensivists, 72.7% had ordered tests for perceived surrogate markers of HIV
      infection in lieu of HIV tests; more than 90% believed these tests were
      sufficiently valid to base clinical decisions on. CONCLUSIONS: Most US
      intensivists have encountered decisionally incapacitated patients for whom HIV
      testing may improve care. Intensivists' decisions to pursue nonconsented testing
      are associated with their personal ethics and often erroneous perceptions of
      state laws, but not with the laws themselves. Uniform standards enabling
      nonconsented HIV testing may minimize inappropriate influences on intensivists'
      decisions and reduce intensivists' reliance on perceived surrogate markers of
      immunodeficiency.

PMID- 18039992
TI  - Low bone mass in premenopausal women with depression.
AB  - BACKGROUND: An increased prevalence of low bone mineral density (BMD) has been
      reported in patients with major depressive disorder (MDD), mostly women. METHODS:
      Study recruitment was conducted from July 1, 2001, to February 29, 2003. We
      report baseline BMD measurements in 89 premenopausal women with MDD and 44
      healthy control women enrolled in a prospective study of bone turnover. The BMD
      was measured by dual-energy x-ray absorptiometry at the spine, hip, and forearm.
      Mean hourly levels of plasma 24-hour cytokines, 24-hour urinary free cortisol,
      and catecholamine excretion were measured in a subset of women. We defined MDD
      according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth
      Edition). RESULTS: The prevalence of low BMD, defined as a T score of less than 
      1, was greater in women with MDD vs controls at the femoral neck (17% vs 2%; P =
      .02) and total hip (15% vs 2%; P = .03) and tended to be greater at the lumbar
      spine (20% vs 9%; P = .14). The mean +/- SD BMD, expressed as grams per square
      centimeters, was lower in women with MDD at the femoral neck (0.849 +/- 0.121 vs
      0.866 +/- 0.094; P = .05) and at the lumbar spine (1.024 +/- 0.117 vs 1.043 +/-
      0.092; P = .05) and tended to be lower at the radius (0.696 +/- 0.049 vs 0.710 +/
      0.055; P = .07). Women with MDD had increased mean levels of 24-hour
      proinflammatory cytokines and decreased levels of anti-inflammatory cytokines.
      CONCLUSIONS: Low BMD is more prevalent in premenopausal women with MDD. The BMD
      deficits are of clinical significance and comparable in magnitude to those
      resulting from established risk factors for osteoporosis, such as smoking and
      reduced calcium intake. The possible contribution of immune or inflammatory
      imbalance to low BMD in premenopausal women with MDD remains to be clarified.

PMID- 18039993
TI  - Opportunity missed: medical consultation, resource use, and quality of care of
      patients undergoing major surgery.
AB  - BACKGROUND: There is growing interest in collaborative management of surgical
      patients. However, few data describe how medical consultation influences quality
      of care or resource use. The objective of this study was to determine whether
      medical consultation improves care in surgical patients. METHODS: Observational
      cohort of patients undergoing surgery between May 1, 2004, and May 31, 2006, at a
      university-based hospital. The outcomes included costs, hospital length of stay,
      use of preventive therapies (such as perioperative beta-blockers) and clinical
      outcomes. RESULTS: Of 1,282 patients, 117 (9.1%) underwent a perioperative
      medical consultation. Consulted patients were of a similar age, sex, and race,
      but more frequently had an American Society of Anesthesiologists score of 4 or
      higher (34.2% vs 13.0%; P < .001), diabetes mellitus (29.1% vs 16.1%; P < .001),
      vascular disease (35.0% vs 10.6%; P < .01), or chronic renal failure (23.9% vs
      5.6%; P < .001). After adjusting for severity of illness and likelihood of
      receiving a consultation, patients were just as likely to have a serum glucose
      level of less than 200 mg/dL (<11.1 mmol/L), receive perioperative beta-blockers,
      or receive venous thromboembolism prophylaxis. Consulted patients had a longer
      adjusted length of stay (12.98% longer; 95% confidence interval, 1.61%-25.61%)
      and higher adjusted costs (24.36% higher; 95% confidence interval, 13.54%
      36.34%). Patients who had a consultation from a generalist did not receive
      different quality of care, but had costs and length of stay similar to
      nonconsulted patients. Our results may be influenced by unaccounted referral bias
      or severity of illness. CONCLUSIONS: Perioperative internal medicine consultation
      produces inconsistent effects on efficiency and quality of care in surgical
      patients. Modifying the consultative model may represent an opportunity to
      improve care.

PMID- 18039995
TI  - Health care access, use of services, and experiences among undocumented Mexicans
      and other Latinos.
AB  - BACKGROUND: We compared access to health care, use of services, and health care
      experiences for Mexicans and other Latinos by citizenship and immigrant
      authorization status. METHODS: We acquired data from the 2003 California Health
      Interview Survey, with 42,044 participants representative of noninstitutionalized
      households. Participants were differentiated by ethnicity/race, national origin,
      and citizenship/immigration authorization status. Outcome measures included
      having a usual source of care, problems in obtaining necessary care, use of
      physician and emergency department care, and 3 experiences with health care.
      Multivariate analyses measured the associations of citizenship/immigration
      authorization status with the outcome measures among foreign-born Mexicans and
      other Latinos vs their US-born counterparts. RESULTS: In multivariate analyses,
      undocumented Mexicans had 1.6 fewer physician visits (P < .01); compared with US
      born Mexicans; other undocumented Latinos had 2.1 fewer visits (P < .01) compared
      with their US-born counterparts. Both undocumented groups were less likely to
      report difficulty obtaining necessary health care than US-born Mexicans (odds
      ratio, 0.68; P < .01) and other US-born Latinos (odds ratio, 0.40; P < .01),
      respectively. Undocumented Mexicans were less likely to have a usual source of
      care (odds ratio, 0.70; P < .01) and were more likely to report negative
      experiences than US-born Mexicans (odds ratio, 1.93; P < .01). Findings were
      similar for other undocumented Latinos, with the exception of having a usual
      source of care. Patterns of access to and use of health care services tended to
      improve with changing legal status. CONCLUSION: In this large sample,
      undocumented Mexicans and other undocumented Latinos reported less use of health
      care services and poorer experiences with care compared with their US-born
      counterparts, after adjustment for confounders in multivariate analyses.

PMID- 18039996
TI  - A framework for tailoring clinical guidelines to comorbidity at the point of
      care.
AB  - BACKGROUND: Evidence is accumulating to suggest that clinical guidelines should
      be modified for patients with comorbidities, yet there is no quantitative and
      objective approach that considers benefits together with risks. METHODS: We
      outline a framework using a payoff time, which we define as the minimum elapsed
      time until the cumulative incremental benefits of a guideline exceed its
      cumulative incremental harms. If the payoff time of a guideline exceeds a
      patient's comorbidity-adjusted life expectancy, then the guideline is unlikely to
      offer a benefit and should be modified. We illustrate the framework by applying
      this method to colorectal cancer screening guidelines for 50-year-old men with
      human immunodeficiency virus (HIV) and 60-year-old women with congestive heart
      failure (CHF). RESULTS: We estimated that colorectal cancer screening payoff
      times for 50-year-old men with HIV would range from 1.9 to 5.0 years and that
      colorectal cancer screening payoff times for 60-year-old women with CHF would
      range from 0.7 to 2.9 years. Because the payoff times for 50-year-old men with
      HIV were lower than their life expectancies (12.5-24.0 years), colorectal cancer
      screening may be beneficial for these patients. In contrast, because payoff times
      for 60-year-old women with CHF were sometimes greater than their life
      expectancies (0.6 to >5 years), colorectal cancer screening is likely to be
      harmful for some of these patients. CONCLUSION: Use of a payoff time calculation
      may be a feasible framework to tailor clinical guidelines to the comorbidity
      profiles of individual patients.

PMID- 18039997
TI  - Where high-risk adults receive influenza vaccine during a shortage.

PMID- 18039998
TI  - Analgesic use and risk of hypertension: concern about bias.

PMID- 18039999
TI  - Phosphorus-related mechanisms of vascular calcification.

PMID- 18040000
TI  - Association between SSRI use and fractures and the effect of confounding by
      indication.

PMID- 18040001
TI  - Selective serotonin reuptake inhibitors and risk of fracture in elderly persons.

PMID- 18040002
TI  - A possible role of recurrent major depression in risk of fracture.

PMID- 18040003
TI  - Arthritis is associated with cardiovascular disease in the users of analgesics
      and nonsteroidal anti-inflammatory drugs.

PMID- 18039994
TI  - Sex, depression, and risk of hospitalization and mortality in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: We sought to determine whether depressive or anxiety symptoms are
      associated with chronic obstructive pulmonary disease (COPD) hospitalization or
      mortality. These data were collected as part of the National Emphysema Treatment
      Trial (NETT), a randomized controlled trial of lung volume reduction surgery vs
      continued medical treatment conducted at 17 clinics across the United States
      between January 29, 1998, and July 31, 2002. METHODS: Prospective cohort study
      among participants in the NETT with emphysema and severe airflow limitation who
      were randomized to medical therapy. Primary outcomes were 1- and 3-year
      mortality, as well as COPD or respiratory-related hospitalization or emergency
      department visit during the 1-year follow-up period. Of 610 patients randomized
      to medical therapy, complete data on hospitalization and mortality were available
      for 3 years of follow-up for 603 patients (98.9%). RESULTS: Depressive symptoms
      were assessed using the Beck Depression Inventory (BDI) questionnaire, and
      anxiety was assessed using the State-Trait Anxiety Inventory. Among 610 subjects,
      40.8% had at least mild to moderate depressive symptoms. Patients in the highest
      quintile of BDI score (BDI score, >or=15) had an increased risk of respiratory
      hospitalization in unadjusted analysis compared with patients in the lowest
      quintile (BDI score, < 5) (odds ratio [OR], 2.26; 95% confidence interval [CI],
      1.30-3.93). After adjustment for disease severity, this relationship was no
      longer statistically significant. The adjusted risk of 3-year mortality was
      increased among those in the highest quintile of BDI score (OR, 2.74; 95% CI,
      1.42-5.29) compared with those in the lowest quintile. Anxiety was not associated
      with hospitalization or mortality in this population. CONCLUSIONS: Depressive
      symptoms are common in patients with severe COPD and are treated in few subjects.
      Depressive symptoms are associated with increased risk for 3-year mortality but
      not 1-year mortality or hospitalization.

PMID- 18040004
TI  - Another possible cause of increased blood pressure in men older than 60 years who
      are taking medications to control musculoskeletal pain.

PMID- 18040005
TI  - A possible overestimation of the effect of aspirin.

PMID- 18040006
TI  - Education research: communication skills for neurology residents: structured
      teaching and reflective practice.
AB  - OBJECTIVE: Despite the importance of communication skills for neurologists,
      specific training in this area at the residency level is often lacking. This
      study aimed to enhance learning of these skills and to encourage reflective
      practice around communication skills. METHODS: A group of 12 neurology residents
      participated in a series of six case-based communication skills workshops. Each
      workshop focused on a particular clinical scenario, including breaking bad news,
      discussing do-not-resuscitate orders, communicating with "difficult" patients,
      disclosing medical errors, obtaining informed consent for neurologic tests and
      procedures, and discussing life-and-death decisions with families of critically
      ill patients. Residents also kept reflective portfolios in which real examples of
      these interactions were recorded. RESULTS: The program was well accepted, and
      residents rated the workshops as effective and relevant to their practice.
      Analysis of residents' portfolios revealed three themes relevant to patient
      physician communication: 1) communication is more successful when adequate time
      is allowed, 2) the ability to empathize with patients and their families is
      essential to successful interactions, and 3) the development of specific
      approaches to challenging scenarios can facilitate effective interactions. The
      portfolios also demonstrated that residents would engage in reflective practice.
      CONCLUSIONS: Targeting of communication skills training around specific clinical
      scenarios using neurologic cases was well accepted and was deemed relevant to
      practice. The use of portfolios may promote lifelong learning in this area.

PMID- 18040007
TI  - Seizure medications and their side effects.

PMID- 18040009
TI  - Treatment of migraine: a headache for the emergency department.

PMID- 18040010
TI  - Upsetting the balance among membrane channels can produce hyperexcitability or
      inexcitability.

PMID- 18040011
TI  - Association of diabetes, homocysteine, and HDL with cognition and disability
      after stroke.
AB  - OBJECTIVE: To delineate factors associated with cognitive function following
      stroke and test the hypothesis that vascular risk factors associated with
      oxidative stress impair recovery. METHOD: We performed a post hoc analysis of the
      extensive longitudinal database from the 3,680 subjects (over 35 years old)
      entered between 1996 and 2003 into the Vitamin Intervention for Stroke Prevention
      trial using a linear mixed effects model. The primary outcome variables were
      scores on the Mini-Mental State Examination (MMSE) and modified Rankin Scale
      (mRS). RESULTS: MMSE and mRS gradually improved during the 2-year follow-up
      period. Increased age and nonwhite race, recurrent stroke, diabetes mellitus,
      left hemisphere cortical lesions, and values of high-density lipoprotein and
      homocysteine were independent predictors of less successful cognitive recovery. A
      strong interaction between homocysteine and age indicated a threshold effect
      beginning in the late 50s. No vitamin treatment effects were identified. Similar
      factors were identified for recovery of disability as assessed by the mRS,
      although there were qualitative and quantitative differences. CONCLUSIONS: The
      finding that diabetes, high-density lipoprotein, and homocysteine predict poorer
      cognitive function and greater disability after stroke is consistent with the
      hypothesis that metabolic stress plays a significant role in the poststroke
      period.

PMID- 18040012
TI  - Risk factor status and vascular events in patients with symptomatic intracranial
      stenosis.
AB  - BACKGROUND: There are limited data on the relationship between control of
      vascular risk factors and vascular events in patients with symptomatic
      intracranial arterial stenosis. METHODS: We utilized the Warfarin Aspirin
      Symptomatic Intracranial Disease study database to analyze vascular and lifestyle
      risk factors at baseline and averaged over the course of the trial. Cutoff levels
      defining good control for each factor were prespecified based on national
      guidelines. Endpoints evaluated included 1) ischemic stroke, myocardial
      infarction, or vascular death or 2) ischemic stroke alone. Univariate
      associations were assessed using the log-rank test and multivariable analysis was
      done using Cox proportional hazards regression. RESULTS: From baseline until year
      2 follow-up, there was not a significant improvement in blood pressure control.
      During the same period, there were improvements in patients with total
      cholesterol <200 mg/dL (54.6% to 79.2%, p < 0.001) or low-density lipoprotein
      <100 mg/dL (28.7% to 55.9%, p < 0.001). Multivariable analysis showed that
      systolic blood pressure >or=140 mm Hg (HR = 1.79, p = 0.0009, 95% confidence
      limits 1.27 to 2.52), no alcohol consumption (HR 1.69, 1.21 to 2.39, p = 0.002),
      and cholesterol >or=200 mg/dL (HR 1.44, 1.004 to 2.07, p = 0.048) were associated
      with an increased risk of stroke, myocardial infarction, or vascular death. The
      same risk factors were predictors of ischemic stroke alone in multivariable
      analysis. CONCLUSIONS: Elevated blood pressure and cholesterol levels in
      symptomatic patients with intracranial stenosis are associated with an increased
      risk of stroke and other major vascular events.

PMID- 18040013
TI  - Five-year mortality in relation to dementia and cognitive function in 95-year
      olds.
AB  - BACKGROUND: Dementia is a known predictor of mortality, but most studies include
      small numbers of participants above age 90. The influence of dementia or
      cognition on mortality in this age group is therefore uncertain. OBJECTIVE: To
      examine 5-year mortality in relation to dementia and cognitive performance at age
      95. METHODS: A population sample of 338 individuals examined at age 95 was
      followed to age 100. Dementia was diagnosed according to DSM-III-R criteria.
      Cognitive function was measured using the Mini-Mental State Examination (MMSE).
      Information on severe physical disorders was obtained from the Swedish Hospital
      Discharge Register, and date of death from the Swedish Population Register.
      RESULTS: Five-year mortality was higher in 95-year-olds with dementia than in 95
      year-olds without dementia (96% vs 73%; p < 0.0001), even when adjusting for
      severe physical disorders. A Cox regression analysis with calculation of
      population attributable risk (PAR), calculated from adjusted relative risks,
      showed that mortality was predicted by dementia (PAR 42%), cardiac disease (PAR
      17%), cancer (PAR 6%), and male sex (PAR 7%), but not by stroke. Among the
      subjects without dementia, cognitive performance measured using the MMSE (n = 133
      with complete tests; 81% of the subjects without dementia) predicted mortality.
      For each point increase in the MMSE, mortality decreased by 13%. CONCLUSIONS: In
      95-year-olds, dementia, as well as cognitive performance in the subjects without
      dementia, influences mortality. When controlling for other severe medical
      conditions we found dementia to be the leading cause of deaths among the oldest
      old. The reason why dementia and cognitive function predict life expectancy
      requires further elucidation.

PMID- 18040014
TI  - Neuropsychological and neurophysiologic effects of carbamazepine and
      levetiracetam.
AB  - BACKGROUND: The relative effects of levetiracetam (LEV) and carbamazepine (CBZ)
      on cognitive and neurophysiologic measures are uncertain. METHODS: The effects of
      LEV and CBZ were compared in healthy adults using a randomized, double-blind, two
      period crossover design. Outcome measures included 11 standard neuropsychological
      tests and the score from a cognitive-neurophysiologic test of attention and
      memory. Evaluations were conducted at screening, baseline pre-drug treatment, end
      of each maintenance phase (4 weeks), and end of each washout period after drug
      treatment. RESULTS: A total of 28 adults (17 women) with mean age of 33 years
      (range 18 to 51) completed the study. Mean maintenance doses (+/-SD) were CBZ =
      564 mg/day (110) and LEV = 2,000 mg/day (0). CBZ was adjusted to mid-range
      therapeutic level. Mean serum levels (+/-SD) were CBZ = 7.5 mcg/mL (1.5) and LEV
      = 32.2 mcg/mL (11.2). An overall composite score including all measures revealed
      worse effects for CBZ compared to LEV (p <or= 0.001) in the primary analysis and
      for CBZ (p <or= 0.001) and LEV (p <or= 0.05) compared to non-drug in secondary
      analyses. Across the 34 individual variables, CBZ was worse than LEV on 44%
      (15/34); none favored CBZ. Compared to the non-drug average, CBZ was worse for
      76% (26/34), and LEV was worse for 12% (4 of 34). Sensitivity and specificity of
      standard neuropsychological tests and the cognitive-neurophysiologic test were
      determined to direct future studies; detection was most accurate by the cognitive
      neurophysiologic test. CONCLUSIONS: Levetiracetam produces fewer untoward
      neuropsychological and neurophysiologic effects than carbamazepine in monotherapy
      at the dosages and timeframes employed in this study.

PMID- 18040015
TI  - Optical coherence tomography and disease subtype in multiple sclerosis.
AB  - OBJECTIVE: To examine retinal nerve fiber layer (RNFL) thickness, macular volumes
      (MV), and visual acuity in multiple sclerosis (MS) eyes, with and without history
      of acute optic neuritis (ON). METHODS: RNFL thickness was measured in 326 MS and
      94 control eyes using optical coherence tomography (OCT). MV and vision testing
      were done in a subset of the cohort. MS subtype was classified as relapsing
      remitting (RRMS, n = 135), primary progressive (PPMS, n = 12), and secondary
      progressive (SPMS, n = 16). RESULTS: MS ON eyes had decreased RNFL thickness
      (84.2 microm) compared to controls (102.7 microm) (p < 0.0001). Unaffected fellow
      eyes of MS ON eyes (93.9 microm) (p < 0.01) and patients with MS with no history
      of ON (95.9 microm) (p < 0.05) also had decreased RNFL. RRMS (94.4 microm) (p <
      0.001), PPMS (88.9 microm) (p < 0.01), and SPMS (81.8 microm) (p < 0.0001)
      (adjusted for age and duration of disease) had decreased RNFL compared to
      controls. There were significant differences in RNFL thickness within quadrants
      of peripapillary retina comparing relapsing to progressive MS subtypes. MV was
      decreased in MS ON eyes (6.2 mm(3)) (p < 0.0001) and SPMS subjects (6.2 mm(3)) (p
      < 0.05) compared to controls (6.8 mm(3)). CONCLUSION: Retinal nerve fiber layer
      (RNFL) is significantly decreased in multiple sclerosis (MS) optic neuritis (ON)
      eyes, unaffected fellow eyes of patients with MS ON, and MS eyes not affected by
      ON in our cohort. Macular volumes (MV) showed a significant decrease in MS ON
      eyes. Progressive MS cases showed more marked decreases in RNFL and MV than
      relapsing-remitting MS. OCT is a promising tool to detect subclinical changes in
      RNFL and MV in patients with MS and should be examined in longitudinal studies as
      a potential biomarker of retinal pathology in MS.

PMID- 18040016
TI  - Guillain-Barre syndrome complicating a Chikungunya virus infection.

PMID- 18040017
TI  - Fertility in women with active epilepsy.

PMID- 18040018
TI  - Reflections: neurology and the humanities. Lost.

PMID- 18040019
TI  - Re: Activities of daily living in frontotemporal dementia and Alzheimer disease.

PMID- 18040020
TI  - Re: Patterns of ocular oscillation in oculopalatal tremor: imaging correlations.

PMID- 18040021
TI  - Not all hypertrophy is created equal.

PMID- 18040022
TI  - Fading sodium channels in failing hearts.

PMID- 18040023
TI  - Adenosine receptors and angiogenesis.

PMID- 18040024
TI  - cGMP-dependent protein kinase I and smooth muscle relaxation: a tale of two
      isoforms.

PMID- 18040025
TI  - Phosphodiesterase type 5: expanding roles in cardiovascular regulation.
AB  - Phosphodiesterase type 5A (PDE5A) selectively hydrolyzes cyclic GMP. Inhibitors
      of PDE5A such as sildenafil are widely used to treat erectile dysfunction, but
      growing evidence supports important roles for the enzyme in both the vasculature
      and heart. In disorders such as cardiac failure, PDE5A upregulation may
      contribute to a decline in cGMP and protein kinase G signaling, exacerbating
      dysfunction. PDE5A plays an important role in the pulmonary vasculature where its
      inhibition benefits patients with pulmonary hypertension. In the heart, PDE5A
      signaling appears compartmentalized, and its inhibition is cardioprotective
      against ischemia-reperfusion and antracycline toxicity, blunts acute adrenergic
      contractile stimulation, and can suppress chronic hypertrophy and dysfunction
      attributable to pressure-overload. In this review, we discuss the molecular
      biology, pharmacology, and physiology of PDE5A, mechanisms of vascular and
      cardiac regulation, and recent evidence supporting the utility of selective PDE5A
      inhibition for the treatment of cardiovascular disorders.

PMID- 18040026
TI  - Osteogenesis associates with inflammation in early-stage atherosclerosis
      evaluated by molecular imaging in vivo.
AB  - BACKGROUND: Arterial calcification is associated with cardiovascular events;
      however, mechanisms of calcification in atherosclerosis remain obscure. METHODS
      AND RESULTS: We tested the hypothesis that inflammation promotes osteogenesis in
      atherosclerotic plaques using in vivo molecular imaging in apolipoprotein E-/-
      mice (20 to 30 weeks old, n=35). A bisphosphonate-derivatized near-infrared
      fluorescent imaging agent (excitation 750 nm) visualized osteogenic activity that
      was otherwise undetectable by x-ray computed tomography. Flow cytometry validated
      the target specifically in osteoblast-like cells. A spectrally distinct near
      infrared fluorescent nanoparticle (excitation 680 nm) was coinjected to
      simultaneously image macrophages. Fluorescence reflectance mapping demonstrated
      an association between osteogenic activity and macrophages in aortas of
      apolipoprotein E-/- mice (R2=0.93). Intravital dual-channel fluorescence
      microscopy was used to further monitor osteogenic changes in inflamed carotid
      arteries at 20 and 30 weeks of age and revealed that macrophage burden and
      osteogenesis concomitantly increased during plaque progression (P<0.01 and
      P<0.001, respectively) and decreased after statin treatment (P<0.0001 and P<0.05,
      respectively). Fluorescence microscopy on cryosections colocalized near-infrared
      fluorescent osteogenic signals with alkaline phosphatase activity, bone
      regulating protein expression, and hydroxyapatite nanocrystals as detected by
      electron microscopy, whereas von Kossa and alizarin red stains showed no evidence
      of calcification. Real-time reverse-transcription polymerase chain reaction
      revealed that macrophage-conditioned media increased alkaline phosphatase mRNA
      expression in vascular smooth muscle cells. CONCLUSIONS: This serial in vivo
      study demonstrates the real-time association of macrophage burden with osteogenic
      activity in early-stage atherosclerosis and offers a cellular-resolution tool to
      identify preclinical microcalcifications.

PMID- 18040027
TI  - Cardioprotective effects of short-term caloric restriction are mediated by
      adiponectin via activation of AMP-activated protein kinase.
AB  - BACKGROUND: Overeating and obesity are major health problems in developed
      countries. Caloric restriction (CR) can counteract the deleterious aspects of
      obesity-related diseases and prolong lifespan. We have demonstrated that short
      term CR improves myocardial ischemic tolerance and increases adiponectin levels.
      Here, we investigated the specific role of adiponectin in CR-induced
      cardioprotection. METHODS AND RESULTS: Adiponectin antisense transgenic (Ad-AS)
      mice and wild-type (WT) mice were randomly assigned to a group fed ad libitum and
      a CR group (90% of caloric intake of ad libitum for 3 weeks, then 65% for 2
      weeks). Isolated perfused mouse hearts were subjected to 25 minutes of ischemia,
      followed by 60 minutes of reperfusion. CR increased serum adiponectin levels by
      84% in WT mice. Gel filtration analysis of the oligomeric complex distribution
      showed that CR produced a marked increase in the high-molecular-weight complex of
      adiponectin in WT mice; in contrast, CR did not change serum adiponectin levels
      or their oligomeric pattern in Ad-AS mice. CR improved the recovery of left
      ventricular function after ischemia/reperfusion and limited infarct size in WT
      mice; these effects were completely abrogated in Ad-AS mice. CR also increased
      the phosphorylated form of AMP-activated protein kinase and acetyl-CoA
      carboxylase in WT but not in Ad-AS mice. Recombinant adiponectin restored CR
      induced cardioprotection in Ad-AS mice, and inhibition of AMP-activated protein
      kinase phosphorylation completely abrogated CR-induced cardioprotection in WT
      mice. CONCLUSIONS: The cardioprotective effects of short-term CR are mediated by
      increased production of adiponectin and the associated activation of AMP
      activated protein kinase.

PMID- 18040028
TI  - Endogenous testosterone and mortality due to all causes, cardiovascular disease,
      and cancer in men: European prospective investigation into cancer in Norfolk
      (EPIC-Norfolk) Prospective Population Study.
AB  - BACKGROUND: The relation between endogenous testosterone concentrations and
      health in men is controversial. METHODS AND RESULTS: We examined the prospective
      relationship between endogenous testosterone concentrations and mortality due to
      all causes, cardiovascular disease, and cancer in a nested case-control study
      based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up
      to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men
      who subsequently died were compared with a control group of 1489 men still alive,
      matched for age and date of baseline visit. Endogenous testosterone
      concentrations at baseline were inversely related to mortality due to all causes
      (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths). Odds
      ratios (95% confidence intervals) for mortality for increasing quartiles of
      endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to
      1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively (P<0.001 for
      trend after adjustment for age, date of visit, body mass index, systolic blood
      pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol
      intake, physical activity, social class, education, dehydroepiandrosterone
      sulfate, androstanediol glucuronide, and sex hormone binding globulin). An
      increase of 6 nmol/L serum testosterone ( approximately 1 SD) was associated with
      a 0.81 (95% confidence interval 0.71 to 0.92, P<0.01) multivariable-adjusted odds
      ratio for mortality. Inverse relationships were also observed for deaths due to
      cardiovascular causes and cancer and after the exclusion of deaths that occurred
      in the first 2 years. CONCLUSIONS: In men, endogenous testosterone concentrations
      are inversely related to mortality due to cardiovascular disease and all causes.
      Low testosterone may be a predictive marker for those at high risk of
      cardiovascular disease.

PMID- 18040029
TI  - Age decreases endothelial progenitor cell recruitment through decreases in
      hypoxia-inducible factor 1alpha stabilization during ischemia.
AB  - BACKGROUND: Advanced age is known to impair neovascularization. Because
      endothelial progenitor cells (EPCs) participate in this process, we examined the
      effects of aging on EPC recruitment and vascular incorporation. METHODS AND
      RESULTS: Murine neovascularization was examined by use of an ischemic flap model,
      which demonstrated aged mice (19 to 24 months) had decreased EPC mobilization
      (percent mobilized 1.4+/-0.2% versus 0.4+/-0.1%, P<0.005) that resulted in
      impaired gross tissue survival compared with young mice (2 to 6 months). This
      decrease correlated with diminished tissue perfusion (P<0.005) and decreased
      CD31+ vascular density (P<0.005). Gender-mismatched bone marrow transplantation
      demonstrated significantly fewer chimeric vessels in aged mice (P<0.05), which
      confirmed a deficit in bone marrow-mediated vasculogenesis. Age had no effect on
      total EPC number in mice or humans. Reciprocal bone marrow transplantations
      confirmed that impaired neovascularization resulted from defects in the response
      of aged tissue to hypoxia and not from intrinsic defects in EPC function. We
      demonstrate that aging decreased hypoxia-inducible factor 1alpha stabilization in
      ischemic tissues because of increased prolyl hydroxylase-mediated hydroxylation
      (P<0.05) and proteasomal degradation. This resulted in a diminished hypoxia
      response, including decreased stromal cell-derived factor 1 (P<0.005) and
      vascular endothelial growth factor (P<0.0004). This effect can be reversed with
      the iron chelator deferoxamine, which results in hypoxia-inducible factor 1alpha
      stabilization and increased tissue survival. CONCLUSIONS: Aging impairs EPC
      trafficking to sites of ischemia through a failure of aged tissues to normally
      activate the hypoxia-inducible factor 1alpha-mediated hypoxia response.

PMID- 18040030
TI  - Can common-type atrial flutter be a sign of an arrhythmogenic substrate in
      paroxysmal atrial fibrillation? Clinical and ablative consequences in patients
      with coexistent paroxysmal atrial fibrillation/atrial flutter.
AB  - BACKGROUND: The coexistence of atrial fibrillation (AF) and atrial flutter (AFL)
      is well recognized. AF precedes the onset of AFL in almost all instances. We
      evaluated the effect of 2 ablation strategies in patients with paroxysmal AF
      (PAF) and AFL. METHODS AND RESULTS: Ninety-eight patients with PAF/AFL were
      prospectively recruited to undergo pulmonary vein cryoisolation (PVI). Those with
      at least 1 episode of sustained common-type AFL were assigned to cavotricuspid
      isthmus cryoablation followed by a 6-week monitoring period and a subsequent PVI
      (n=36; group I). Patients with PAF only underwent PVI (n=62; group II). The study
      included 76 men with a mean age of 50+/-10 years. Most patients (76 [78%]) had no
      structural heart disease. When the 2 groups were compared, residual AF after a
      blanking period of 3 months after PVI occurred in 24 patients (67%) in group I
      versus 7 (11%) in group II (P<0.05). CONCLUSIONS: In patients with PAF and no
      documented common-type AFL, PVI alone prevented the occurrence of AF in 82%,
      whereas in patients with AFL/PAF, cavotricuspid isthmus cryoablation and PVI were
      used successfully to treat sustained common-type AFL but appeared to be
      insufficient to prevent recurrences of AF. In this population, AFL can be a sign
      that non-pulmonary vein triggers are the culprit behind AF or that sufficient
      electrical remodeling has already occurred in both atria, and thus a strategy
      that includes substrate modification may be required.

PMID- 18040031
TI  - Altered plasma versus vascular biopterins in human atherosclerosis reveal
      relationships between endothelial nitric oxide synthase coupling, endothelial
      function, and inflammation.
AB  - BACKGROUND: Tetrahydrobiopterin (BH4) is a key regulator of endothelial nitric
      oxide synthase (eNOS) activity and coupling. However, the extent to which
      vascular and/or systemic BH4 levels are altered in human atherosclerosis and the
      importance of BH4 bioavailability in determining endothelial function and
      oxidative stress remain unclear. We sought to define the relationships between
      plasma and vascular biopterin levels in patients with coronary artery disease and
      to determine how BH4 levels affect endothelial function, eNOS coupling, and
      vascular superoxide production. METHODS AND RESULTS: Samples of saphenous veins
      and internal mammary arteries were collected from 219 patients with coronary
      artery disease undergoing coronary artery bypass grafting. We determined plasma
      and vascular levels of biopterins, vasomotor responses to acetylcholine, and
      vascular superoxide production in the presence and absence of the eNOS inhibitor
      N(G)-nitro-L-arginine methyl ester. High vascular BH4 was associated with greater
      vasorelaxations to acetylcholine (P<0.05), whereas high plasma BH4 was associated
      with lower vasorelaxations in response to acetylcholine (P<0.05). Furthermore, an
      inverse association was observed between plasma and vascular biopterins (P<0.05
      for both saphenous veins and internal mammary arteries). High vascular (but not
      plasma) BH4 was associated with reduced total and N(G)-nitro-L-arginine methyl
      ester-inhibitable superoxide, suggesting improved eNOS coupling. Finally, plasma
      but not vascular biopterin levels were correlated with plasma C-reactive protein
      levels (P<0.001). CONCLUSIONS: An inverse association exists between plasma and
      vascular biopterins in patients with coronary artery disease. Vascular but not
      plasma BH4 is an important determinant of eNOS coupling, endothelium-dependent
      vasodilation, and superoxide production in human vessels, whereas plasma
      biopterins are a marker of systemic inflammation.

PMID- 18040032
TI  - Viewpoint: Petros Nihoyannopoulos, MD, FRCP, FESC. Interview by Monika Polak.

PMID- 18040033
TI  - Images in cardiovascular medicine. Direct visualization of a transcatheter
      pulmonary valve implantation within the visible heart: a glimpse into the future.

PMID- 18040034
TI  - Letter by Testa et al regarding article, "Pathological correlates of late drug
      eluting stent thrombosis: strut coverage as a marker of endothelialization".

PMID- 18040035
TI  - Does active rescuer ventilation have a place during basic cardiopulmonary
      resuscitation?

PMID- 18040036
TI  - Ablation for atrial fibrillation: can we decrease thromboembolism without
      increasing the risk for bleeding?

PMID- 18040037
TI  - Genetic wiring diagram of the cardiac conduction system.

PMID- 18040038
TI  - Blood transfusion in cardiac surgery: a silent epidemic revisited.

PMID- 18040039
TI  - Role of tissue Doppler and strain echocardiography in current clinical practice.

PMID- 18040040
TI  - An electrocardiogram should not be included in routine preparticipation screening
      of young athletes.

PMID- 18040041
TI  - Electrocardiograms should be included in preparticipation screening of athletes.

PMID- 18040042
TI  - Structure of the Nitrosomonas europaea Rh protein.
AB  - Amt/MEP/Rh proteins are a family of integral membrane proteins implicated in the
      transport of NH3, CH(2)NH2, and CO2. Whereas Amt/MEP proteins are agreed to
      transport ammonia (NH3/NH4+), the primary substrate for Rh proteins has been
      controversial. Initial studies suggested that Rh proteins also transport ammonia,
      but more recent evidence suggests that they transport CO2. Here we report the
      first structure of an Rh family member, the Rh protein from the
      chemolithoautotrophic ammonia-oxidizing bacterium Nitrosomonas europaea. This Rh
      protein exhibits a number of similarities to its Amt cousins, including a
      trimeric oligomeric state, a central pore with an unusual twin-His site in the
      middle, and a Phe residue that blocks the channel for small-molecule transport.
      However, there are some significant differences, the most notable being the
      presence of an additional cytoplasmic C-terminal alpha-helix, an increased number
      of internal proline residues along the transmembrane helices, and a specific set
      of residues that appear to link the C-terminal helix to Phe blockage. This latter
      linkage suggests a mechanism in which binding of a partner protein to the C
      terminus could regulate channel opening. Another difference is the absence of the
      extracellular pi-cation binding site conserved in Amt/Mep structures. Instead,
      CO2 pressurization experiments identify a CO2 binding site near the intracellular
      exit of the channel whose residues are highly conserved in all Rh proteins,
      except those belonging to the Rh30 subfamily. The implications of these findings
      on the functional role of the human Rh antigens are discussed.

PMID- 18040043
TI  - Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1
      mediated resistance to apoptosis.
AB  - Elevated expression of members of the BCL-2 pro-survival family of proteins can
      confer resistance to apoptosis in cancer cells. Small molecule obatoclax (GX15
      070), which is predicted to occupy a hydrophobic pocket within the BH3 binding
      groove of BCL-2, antagonizes these members and induces apoptosis, dependent on
      BAX and BAK. Reconstitution in yeast confirmed that obatoclax acts on the pathway
      and overcomes BCL-2-, BCL-XL-, BCL-w-, and MCL-1-mediated resistance to BAX or
      BAK. The compound potently interfered with the direct interaction between MCL-1
      and BAK in intact mitochondrial outer membrane and inhibited the association
      between MCL-1 and BAK in intact cells. MCL-1 has been shown to confer resistance
      to the BCL-2/BCL-XL/BCL-w-selective antagonist ABT-737 and to the proteasome
      inhibitor bortezomib. In both cases, this resistance was overcome by obatoclax.
      These findings support a rational clinical development opportunity for the
      compound in cancer indications or treatments where MCL-1 contributes to
      resistance to cell killing.

PMID- 18040044
TI  - Assembly and structural properties of glucocorticoid-induced TNF receptor ligand:
      Implications for function.
AB  - Glucocorticoid-induced TNF receptor ligand (GITRL), a recently identified member
      of the TNF family, binds to its receptor GITR on both effector and regulatory T
      cells and generates positive costimulatory signals implicated in a wide range of
      T cell functions. Structural analysis reveals that the human GITRL (hGITRL)
      ectodomain self-assembles into an atypical expanded homotrimer with sparse
      monomer-monomer interfaces. Consistent with the small intersubunit interfaces,
      hGITRL exhibits a relatively weak tendency to trimerize in solution and displays
      a monomer-trimer equilibrium not reported for other TNF family members. This
      unique assembly behavior has direct implications for hGITRL-GITR signaling,
      because enforced trimerization of soluble hGITRL ectodomain results in an
      approximately 100-fold increase in its receptor binding affinity and also in
      enhanced costimulatory activity. The apparent reduction in affinity that is the
      consequence of this dynamic equilibrium may represent a mechanism to realize the
      biologically optimal level of signaling through the hGITRL-GITR pathway, as
      opposed to the maximal achievable level.

PMID- 18040045
TI  - Does the H index have predictive power?
AB  - Bibliometric measures of individual scientific achievement are of particular
      interest if they can be used to predict future achievement. Here we report
      results of an empirical study of the predictive power of the h index compared
      with other indicators. Our findings indicate that the h index is better than
      other indicators considered (total citation count, citations per paper, and total
      paper count) in predicting future scientific achievement. We discuss reasons for
      the superiority of the h index.

PMID- 18040046
TI  - Laforin is a glycogen phosphatase, deficiency of which leads to elevated
      phosphorylation of glycogen in vivo.
AB  - Lafora disease is a progressive myoclonus epilepsy with onset typically in the
      second decade of life and death within 10 years. Lafora bodies, deposits of
      abnormally branched, insoluble glycogen-like polymers, form in neurons, muscle,
      liver, and other tissues. Approximately half of the cases of Lafora disease
      result from mutations in the EPM2A gene, which encodes laforin, a member of the
      dual-specificity protein phosphatase family that additionally contains a glycogen
      binding domain. The molecular basis for the formation of Lafora bodies is
      completely unknown. Glycogen, a branched polymer of glucose, contains a small
      amount of covalently linked phosphate whose origin and function are obscure. We
      report here that recombinant laforin is able to release this phosphate in vitro,
      in a time-dependent reaction with an apparent K(m) for glycogen of 4.5 mg/ml.
      Mutations of laforin that disable the glycogen binding domain also eliminate its
      ability to dephosphorylate glycogen. We have also analyzed glycogen from a mouse
      model of Lafora disease, Epm2a(-/-) mice, which develop Lafora bodies in several
      tissues. Glycogen isolated from these mice had a 40% increase in the covalent
      phosphate content in liver and a 4-fold elevation in muscle. We propose that
      excessive phosphorylation of glycogen leads to aberrant branching and Lafora body
      formation. This study provides a molecular link between an observed biochemical
      property of laforin and the phenotype of a mouse model of Lafora disease. The
      results also have important implications for glycogen metabolism generally.

PMID- 18040047
TI  - Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics
      by cAMP.
AB  - cAMP is well known to regulate exocytosis in various secretory cells, but the
      precise mechanism of its action remains unknown. Here, we examine the role of
      cAMP signaling in the exocytotic process of insulin granules in pancreatic beta
      cells. Although activation of cAMP signaling alone does not cause fusion of the
      granules to the plasma membrane, it clearly potentiates both the first phase (a
      prompt, marked, and transient increase) and the second phase (a moderate and
      sustained increase) of glucose-induced fusion events. Interestingly, all granules
      responsible for this potentiation are newly recruited and immediately fused to
      the plasma membrane without docking (restless newcomer). Importantly, cAMP
      potentiated fusion events in the first phase of glucose-induced exocytosis are
      markedly reduced in mice lacking the cAMP-binding protein Epac2 (Epac2(ko/ko)).
      In addition, the small GTPase Rap1, which is activated by cAMP specifically
      through Epac2 in pancreatic beta cells, mediates cAMP-induced insulin secretion
      in a protein kinase A-independent manner. We also have developed a simulation
      model of insulin granule movement in which potentiation of the first phase is
      associated with an increase in the insulin granule density near the plasma
      membrane. Taken together, these data indicate that Epac2/Rap1 signaling is
      essential in regulation of insulin granule dynamics by cAMP, most likely by
      controlling granule density near the plasma membrane.

PMID- 18040048
TI  - Long-term evolution of transposable elements.
AB  - Transposable elements are often considered parasitic DNA sequences, able to
      invade the genome of their host thanks to their self-replicating ability. This
      colonization process has been extensively studied, both theoretically and
      experimentally, but their long-term coevolution with the genomes is still poorly
      understood. In this work, we aim to challenge previous population genetics models
      by considering features of transposable elements as quantitative, rather than
      discrete, variables. We also describe more realistic transposable element
      dynamics by accounting for the variability of the insertion effect, from
      deleterious to adaptive, as well as mutations leading to a loss of transposition
      activity and to nonautonomous copies. Individual-based simulations of the
      behavior of a transposable-element family over several thousand generations show
      different ways in which active or inactive copies can be maintained for a very
      long time. Results reveal an unexpected impact of genetic drift on the "junk DNA"
      content of the genome and strongly question the likelihood of the sustainable
      long-term stable transposition-selection equilibrium on which numerous previous
      works were based.

PMID- 18040049
TI  - Syndecan-3 is a dendritic cell-specific attachment receptor for HIV-1.
AB  - Dendritic cells (DCs) efficiently capture HIV-1 and mediate transmission to T
      cells, but the underlying molecular mechanism is still being debated. The C-type
      lectin DC-SIGN is important in HIV-1 transmission by DCs. However, various
      studies strongly suggest that another HIV-1 receptor on DCs is involved in the
      capture of HIV-1. Here we have identified syndecan-3 as a major HIV-1 attachment
      receptor on DCs. Syndecan-3 is a DC-specific heparan sulfate (HS) proteoglycan
      that captures HIV-1 through interaction with the HIV-1 envelope glycoprotein
      gp120. Syndecan-3 stabilizes the captured virus, enhances DC infection in cis,
      and promotes transmission to T cells. Removal of the HSs from the cell surface by
      heparinase III or by silencing syndecan-3 by siRNA partially inhibited HIV-1
      transmission by immature DCs, whereas neutralizing both syndecan-3 and DC-SIGN
      completely abrogated HIV-1 capture and subsequent transmission. Thus, HIV-1
      exploits both syndecan-3 and DC-SIGN to mediate HIV-1 transmission, and an
      effective microbicide should target both syndecan-3 and DC-SIGN on DCs to prevent
      transmission.

PMID- 18040050
TI  - Two-dimensional infrared spectra reveal relaxation of the nonnucleoside inhibitor
      TMC278 complexed with HIV-1 reverse transcriptase.
AB  - The two nitrile groups at the wings of the nonnucleoside HIV-1 reverse
      transcriptase (RT) inhibitor TMC278 are both identified in high-sensitivity 2D IR
      spectroscopy experiments of the HIV-1 RT/TMC278 complex. The vibrational spectra
      indicate that the two arms of the inhibitor sense quite different environments
      within the hydrophobic pocket. The vibrational relaxation of the two arms are
      almost equal at 3 ps from model studies. The 2D IR spectra expose a significant
      distribution of nitrile frequencies that diffuse at equilibrium on ultrafast time
      scales ranging from hundreds of femtoseconds to tens of picoseconds. The slow
      spectral diffusion of the cyanovinyl arm of the inhibitor is attributed to its
      interaction with the backbone and side chains in the hydrophobic tunnel. The
      results show that the inhibitor cyano modes lose memory of their structural
      configurations relative to the hydrophobic pocket within tens of picoseconds. The
      cross-peaks between the two arms of the drug are tentatively attributed to
      relaxation of the nitrile state with both arms excited.

PMID- 18040051
TI  - Distinguishing protein-coding and noncoding genes in the human genome.
AB  - Although the Human Genome Project was completed 4 years ago, the catalog of human
      protein-coding genes remains a matter of controversy. Current catalogs list a
      total of approximately 24,500 putative protein-coding genes. It is broadly
      suspected that a large fraction of these entries are functionally meaningless
      ORFs present by chance in RNA transcripts, because they show no evidence of
      evolutionary conservation with mouse or dog. However, there is currently no
      scientific justification for excluding ORFs simply because they fail to show
      evolutionary conservation: the alternative hypothesis is that most of these ORFs
      are actually valid human genes that reflect gene innovation in the primate
      lineage or gene loss in the other lineages. Here, we reject this hypothesis by
      carefully analyzing the nonconserved ORFs-specifically, their properties in other
      primates. We show that the vast majority of these ORFs are random occurrences.
      The analysis yields, as a by-product, a major revision of the current human
      catalogs, cutting the number of protein-coding genes to approximately 20,500.
      Specifically, it suggests that nonconserved ORFs should be added to the human
      gene catalog only if there is clear evidence of an encoded protein. It also
      provides a principled methodology for evaluating future proposed additions to the
      human gene catalog. Finally, the results indicate that there has been relatively
      little true innovation in mammalian protein-coding genes.

PMID- 18040052
TI  - Screening for compounds that induce apoptosis of cancer cells grown as
      multicellular spheroids.
AB  - Screening and initial characterization of anticancer drugs are typically
      performed using monolayer cultures of tumor cells. It is well established that
      such monolayer cultures do not represent the characteristics of 3-dimensional
      solid tumors. The multicellular tumor spheroid model is of intermediate
      complexity between in vivo tumors and in vitro monolayer cultures and would be
      more suitable for drug screening. The authors describe a procedure in which
      multicellular spheroids are used to screen for compounds that induce tumor cell
      apoptosis. Multicellular spheroids were generated in 96-well plates, and
      apoptosis was determined using the M30-Apoptosense enzyme-linked immunosorbent
      assay method. A Z' factor of approximately 0.5 was observed for HCT116 colon
      carcinoma spheroids using staurosporine to induce apoptosis. This procedure is
      attractive for secondary screening of hits from larger cell-based screens.

PMID- 18040053
TI  - Phage display screening of epithelial cell monolayers treated with EGTA:
      identification of peptide FDFWITP that modulates tight junction activity.
AB  - Phage display was used to screen for peptides that modulate the activity of
      epithelial cell tight junctions. Panning with a phage library that displays
      random 7-mers was performed using monolayers of human bronchial epithelial cells
      (16HBE14o(-)) treated with a calcium chelator, ethylene glycol-bis(2
      aminoethylether)- N, N, N', N'-tetraacetic acid (EGTA), to increase accessibility
      to the junctional complex/paracellular space, followed by subtractive panning. A
      novel peptide, FDFWITP, identified as a potential tight junction modulator, was
      synthesized in linear and cyclic forms with lysine residues added to improve
      solubility. The cyclic form of the peptide reduced transepithelial electrical
      resistance (TER) in a concentration-dependent manner (80% reduction at 100 microM
      and 95% reduction at 500 microM) and was reversible within 2 h; the linear form
      only affected TER at the highest concentration. Interestingly, the constrained
      peptide did not increase permeation of the model small molecule, fluorescein. The
      highly selective activity of FDFWITP supports the hypothesis that ions and small
      molecules may be transported paracellularly across tight junctions by separate
      pathways.

PMID- 18040054
TI  - Cancer risk management practices of noncarriers within BRCA1/2 mutation positive
      families in the Kathleen Cuningham Foundation Consortium for Research into
      Familial Breast Cancer.
AB  - PURPOSE: Women from BRCA mutation-positive families who do not carry the family
      specific mutation are generally at average cancer risk and therefore do not
      require intensive risk management. METHODS: Participants were female noncarriers
      from BRCA mutation-positive families who had responded to 3 yearly follow-up
      questionnaires and had chosen to either receive or not receive their genetic test
      result. In the former group, undertaking mammography younger than age 40 years or
      more than once every 2 years, clinical breast examination (CBE) more than yearly,
      breast self-examination (BSE) more than monthly, or any transvaginal ultrasound
      (TVU) or CA-125 was considered overscreening. Screening behaviors of women who
      did and did not know their genetic test result were compared. Logistic regression
      and nonparametric analyses were performed to identify demographic and
      psychosocial factors (respectively) associated with overscreening. RESULTS: Of
      325 eligible women, 116 knew their mutation status and 209 did not. For the first
      group, proportions overscreening were mammography, 53%; CBE, 10%; BSE, 11%; TVU,
      7%; and CA-125, 10%. There were no significant differences in screening behaviors
      between the groups. In those aware of their mutation status, parous women were
      more likely to overuse mammography (odds ratio [OR] = 4.4; 95% CI, 1.1 to 17; P =
      .03) and women with one or more first-degree relative with ovarian cancer (OC)
      were more likely to overuse OC screening (TVU: OR = 6.00; 95% CI, 1.0 to 35.1; P
      = .047, and CA-125: OR = 6.50; 95% CI, 1.49 to 28.4; P = .013). CONCLUSION: The
      reasons for overuse of screening (particularly mammography) by mutation
      noncarriers require additional elucidation given the potential for harm.

PMID- 18040055
TI  - The Journal of General Physiology on PubMed Central.

PMID- 18040056
TI  - How to turn the reaction coordinate into time.

PMID- 18040057
TI  - Acetylcholine receptor gating at extracellular transmembrane domain interface:
      the cys-loop and M2-M3 linker.
AB  - Acetylcholine receptor channel gating is a propagated conformational cascade that
      links changes in structure and function at the transmitter binding sites in the
      extracellular domain (ECD) with those at a "gate" in the transmembrane domain
      (TMD). We used Phi-value analysis to probe the relative timing of the gating
      motions of alpha-subunit residues located near the ECD-TMD interface. Mutation of
      four of the seven amino acids in the M2-M3 linker (which connects the pore-lining
      M2 helix with the M3 helix), including three of the four residues in the core of
      the linker, changed the diliganded gating equilibrium constant (K(eq)) by up to
      10,000-fold (P272 > I274 > A270 > G275). The average Phi-value for the whole
      linker was approximately 0.64. One interpretation of this result is that the
      gating motions of the M2-M3 linker are approximately synchronous with those of
      much of M2 (approximately 0.64), but occur after those of the transmitter binding
      site region (approximately 0.93) and loops 2 and 7 (approximately 0.77). We also
      examined mutants of six cys-loop residues (V132, T133, H134, F135, P136, and
      F137). Mutation of V132, H134, and F135 changed K(eq) by 2800-, 10-, and 18-fold,
      respectively, and with an average Phi-value of 0.74, similar to those of other
      cys-loop residues. Even though V132 and I274 are close, the energetic coupling
      between I and V mutants of these positions was small (< or =0.51 kcal mol(-1)).
      The M2-M3 linker appears to be the key moving part that couples gating motions at
      the base of the ECD with those in TMD. These interactions are distributed along
      an approximately 16-A border and involve about a dozen residues.

PMID- 18040058
TI  - Acetylcholine receptor gating at extracellular transmembrane domain interface:
      the "pre-M1" linker.
AB  - Charged residues in the beta10-M1 linker region ("pre-M1") are important in the
      expression and function of neuromuscular acetylcholine receptors (AChRs). The
      perturbation of a salt bridge between pre-M1 residue R209 and loop 2 residue E45
      has been proposed as being a principle event in the AChR gating conformational
      "wave." We examined the effects of mutations to all five residues in pre-M1
      (positions M207-P211) plus E45 in loop 2 in the mouse alpha(1)-subunit. M207,
      Q208, and P211 mutants caused small (approximately threefold) changes in the
      gating equilibrium constant (K(eq)), but the changes for R209, L210, and E45 were
      larger. Of 19 different side chain substitutions at R209 on the wild-type
      background, only Q, K, and H generated functional channels, with the largest
      change in K(eq) (67-fold) from R209Q. Various R209 mutants were functional on
      different E45 backgrounds: H, Q, and K (E45A), H, A, N, and Q (E45R), and K, A,
      and N (E45L). Phi values for R209 (on the E45A background), L210, and E45 were
      0.74, 0.35, and 0.80, respectively. Phi values for R209 on the wt and three other
      backgrounds could not be estimated because of scatter. The average coupling
      energy between 209/45 side chains (six different pairs) was only -0.33 kcal/mol
      (for both alpha subunits, combined). Pre-M1 residues are important for expression
      of functional channels and participate in gating, but the relatively modest
      changes in closed- vs. open-state energy caused mutations, the weak coupling
      energy between these residues and the functional activity of several unmatched
      charge pairs are not consistent with the perturbation of a salt bridge between
      R209 and E45 playing the principle role in gating.

PMID- 18040059
TI  - Acetylcholine receptor gating: movement in the alpha-subunit extracellular
      domain.
AB  - Acetylcholine receptor channel gating is a brownian conformational cascade in
      which nanometer-sized domains ("Phi blocks") move in staggering sequence to link
      an affinity change at the transmitter binding sites with a conductance change in
      the pore. In the alpha-subunit, the first Phi-block to move during channel
      opening is comprised of residues near the transmitter binding site and the second
      is comprised of residues near the base of the extracellular domain. We used the
      rate constants estimated from single-channel currents to infer the gating
      dynamics of Y127 and K145, in the inner and outer sheet of the beta-core of the
      alpha-subunit. Y127 is at the boundary between the first and second Phi blocks,
      at a subunit interface. alphaY127 mutations cause large changes in the gating
      equilibrium constant and with a characteristic Phi-value (Phi = 0.77) that places
      this residue in the second Phi-block. We also examined the effect on gating of
      mutations in neighboring residues deltaI43 (Phi = 0.86), epsilonN39 (complex
      kinetics), alphaI49 (no effect) and in residues that are homologous to alphaY127
      on the epsilon, beta, and delta subunits (no effect). The extent to which
      alphaY127 gating motions are coupled to its neighbors was estimated by measuring
      the kinetic and equilibrium constants of constructs having mutations in alphaY127
      (in both alpha subunits) plus residues alphaD97 or deltaI43. The magnitude of the
      coupling between alphaD97 and alphaY127 depended on the alphaY127 side chain and
      was small for both H (0.53 kcal/mol) and C (-0.37 kcal/mol) substitutions. The
      coupling across the single alpha-delta subunit boundary was larger (0.84
      kcal/mol). The Phi-value for K145 (0.96) indicates that its gating motion is
      correlated temporally with the motions of residues in the first Phi-block and is
      not synchronous with those of alphaY127. This suggests that the inner and outer
      sheets of the alpha-subunit beta-core do not rotate as a rigid body.

PMID- 18040060
TI  - Voltage-dependent dynamic FRET signals from the transverse tubules in mammalian
      skeletal muscle fibers.
AB  - Two hybrid voltage-sensing systems based on fluorescence resonance energy
      transfer (FRET) were used to record membrane potential changes in the transverse
      tubular system (TTS) and surface membranes of adult mice skeletal muscle fibers.
      Farnesylated EGFP or ECFP (EGFP-F and ECFP-F) were used as immobile FRET donors,
      and either non-fluorescent (dipicrylamine [DPA]) or fluorescent (oxonol dye
      DiBAC(4)(5)) lipophilic anions were used as mobile energy acceptors. Flexor
      digitorum brevis (FDB) muscles were transfected by in vivo electroporation with
      pEGFP-F and pECFP-F. Farnesylated fluorescent proteins were efficiently expressed
      in the TTS and surface membranes. Voltage-dependent optical signals resulting
      from resonance energy transfer from fluorescent proteins to DPA were named QRET
      transients, to distinguish them from FRET transients recorded using DiBAC(4)(5).
      The peak DeltaF/F of QRET transients elicited by action potential stimulation is
      twice larger in fibers expressing ECFP-F as those with EGFP-F (7.1% vs. 3.6%).
      These data provide a unique experimental demonstration of the importance of the
      spectral overlap in FRET. The voltage sensitivity of QRET and FRET signals was
      demonstrated to correspond to the voltage-dependent translocation of the charged
      acceptors, which manifest as nonlinear components in current records. For DPA,
      both electrical and QRET data were predicted by radial cable model simulations in
      which the maximal time constant of charge translocation was 0.6 ms. FRET signals
      recorded in response to action potentials in fibers stained with DiBAC(4)(5)
      exhibit DeltaF/F amplitudes as large as 28%, but their rising phase was slower
      than those of QRET signals. Model simulations require a time constant for charge
      translocation of 1.6 ms in order to predict current and FRET data. Our results
      provide the basis for the potential use of lipophilic ions as tools to test for
      fast voltage-dependent conformational changes of membrane proteins in the TTS.

PMID- 18040061
TI  - The relationship of stress, impulsivity, and beliefs to drug use severity in a
      sample of women prison inmates.
AB  - There is a paucity of research examining substance abuse issues among women
      prisoners. This study explored relationships between perceived stress,
      impulsivity, and beliefs in the efficacy of drugs as these variables pertain to
      self-reported drug use severity. Women prisoners (N = 100) participated in
      structured face-to-face interviews based on established research instruments.
      Although there was no significant correlation between demographic characteristics
      and substance use severity, positive relationships were found between substance
      use severity, perceived stress, impulsivity, and beliefs. A multiple linear model
      was estimated regressing drug use severity on beliefs, impulsivity, and perceived
      stress. Only the measures of beliefs and impulsivity were significant correlates
      of drug use severity. Implications are discussed for prison substance abuse
      programming and future research.

PMID- 18040063
TI  - The human red blood cell proteome and interactome.
AB  - The red blood cell or erythrocyte is easily purified, readily available, and has
      a relatively simple structure. Therefore, it has become a very well studied cell
      in terms of protein composition and function. RBC proteomic studies performed
      over the last five years, by several laboratories, have identified 751 proteins
      within the human erythrocyte. As RBCs contain few internal structures, the
      proteome will contain far fewer proteins than nucleated cells. In this
      minireview, we summarize the current knowledge of the RBC proteome, discuss
      alterations in this partial proteome in varied human disease states, and
      demonstrate how in silico studies of the RBC interactome can lead to considerable
      insight into disease diagnosis, severity, and drug or gene therapy response. To
      make these latter points we focus on what is known concerning changes in the RBC
      proteome in Sickle Cell Disease.

PMID- 18040064
TI  - Inflammation and oxidative stress in obstructive sleep apnea syndrome.
AB  - Similar to obesity, with which it is closely associated, obstructive sleep apnea
      syndrome (OSAS) is rapidly becoming a worldwide epidemic. Current knowledge of
      its pathogenesis has been significantly enriched by numerous experimental studies
      that have demonstrated an important role of oxidative stress and inflammation.
      Furthermore, new and exciting data strongly connect these two components in the
      perpetuation of the condition via the overexpression of nuclear factor kappaB.
      Experimental data support the hypothesis that nutrition might represent a
      promising future approach with antioxidants currently being good candidates for
      the modulation of cardiovascular sequelae, although weight reduction and
      controlled positive airway pressure remain the only established treatments for
      OSAS. We discuss herein the recent literature that illustrates these new
      paradigms and speculate on possible implications and future scenarios.

PMID- 18040065
TI  - Effects of dexrazoxane and amifostine on evolution of Doxorubicin cardiomyopathy
      in vivo.
AB  - Doxorubicin is one of the most active drugs in oncology, with cardiotoxicity as a
      serious side effect of its application. The aim of this study was to investigate
      dexrazoxane and amifostine impact on the evolution of myocardial changes induced
      by doxorubicin. BalbC female mice were treated with doxorubicin only (10 mg/kg,
      single intravenous push), or with dexrazoxane (200 mg/kg, intraperitoneal [ip])
      or amifostine (200 mg/kg, ip) 60 mins or 30 mins prior to treatment with
      doxorubicin, respectively. Blood sampling for determination of conventional serum
      marker activity was performed 48 hrs later. The grade of histopathology changes
      was evaluated by light microscopy 1.5 and 3 months after treatments using the
      Billingham scoring method. Control groups consisted of nontreated mice. After
      doxorubicin-only treatment, the grade of heart tissue damage was found to
      increase in the period between 1.5 and 3 months. A similar but less intense
      progression was also detected in amifostine-pretreated animals, with significant
      difference among median Billingham scores between the two time points. The
      pretreatment with dexrazoxane suspended expansion of tissue lesions in time.
      Changes in serum enzyme activity revealed two correlations: the greater reduction
      in alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) leakage is associated with a
      lower percentage of damaged tissue, and the creatine kinase to alpha-HBDH percent
      of difference ratio being greater than one is correlated with limited spreading
      of pathological lesions. Our results indicate that the development of doxorubicin
      induced heart failure is based on a slow and persistent expansion of pathological
      process even long after the completion of the treatment. Dexrazoxane has proved
      to be successful and superior over amifostine against such an evolution of
      doxorubicin cardiomyopathy.

PMID- 18040066
TI  - Polygoni cuspidati radix inhibits the activation of Syk kinase in mast cells for
      antiallergic activity.
AB  - The antiallergic activity of Polygoni cuspidati radix (PR) and the mechanism of
      action by which it functions were investigated in this study. The extract of PR
      exhibited potent inhibitory activity in mast cells; its IC50 values were 62 +/-
      2.1 microg/ml for RBL-2H3 mast cells and 46 +/- 3.2 microg/m for bone marrow
      derived mast cells by antigen stimulation, and it also suppressed the expression
      of tumor necrosis factor-alpha and interleukin-4 in RBL-2H3 cells. According to
      the in vivo animal allergy model, it inhibited a local allergic reaction, passive
      cutaneous anaphylaxis, in a dose-dependent manner. With regard to its mechanism
      of action, PR inhibited the activating phosphorylation of Syk, a key signaling
      protein for the activation of mast cells. It also suppressed Akt and the mitogen
      activated protein kinases ERK1/2, p38, and JNK, which are critical for the
      production of various inflammatory cytokines in mast cells. The results of the
      study indicate that the antiallergic activity of PR is mediated through the
      inhibition of histamine release and allergic cytokine production by the
      inhibition of Syk activating phosphorylation in mast cells.

PMID- 18040067
TI  - Nitrosyl-cobinamide, a new and direct nitric oxide releasing drug effective in
      vivo.
AB  - A limited number of nitric oxide (NO)-generating drugs are available for clinical
      use for acute and chronic conditions. Most of these agents are organic nitrates,
      which do not directly release NO; tolerance to the drugs develops, in part, as a
      consequence of their conversion to NO. We synthesized nitrosyl-cobinamide (NO
      Cbi) from cobinamide, a structural analog of cobalamin (vitamin B12). NO-Cbi is a
      direct NO-releasing agent that we found was stable in water, but under
      physiologic conditions, it released NO with a half-life of 30 mins to 1 h. We
      show in five different biological systems that NO-Cbi is an effective NO
      releasing drug. First, in cultured rat vascular smooth muscle cells, NO-Cbi
      induced phosphorylation of vasodilator-stimulated phosphoprotein, a downstream
      target of cGMP and cGMP-dependent protein kinase. Second, in isolated Drosophila
      melanogaster Malpighian tubules, NO-Cbi-stimulated fluid secretion was similar to
      that stimulated by Deta-NONOate and a cGMP analog. Third, in isolated mouse
      hearts, NO-Cbi increased coronary flow much more potently than nitroglycerin.
      Fourth, in contracted mouse aortic rings, NO-Cbi induced relaxation, albeit to a
      lesser extent than sodium nitroprusside. Fifth, in intact mice, a single NO-Cbi
      injection rapidly reduced blood pressure, and blood pressure returned to normal
      after 45 mins; repeated NO-Cbi injections induced the expected fall in blood
      pressure. These studies indicate that NO-Cbi is a useful NO donor that can be
      used experimentally in the laboratory; moreover, it could be developed into a
      vasodilating drug for treating hypertension and potentially other diseases such
      as angina and congestive heart failure.

PMID- 18040068
TI  - QiHong prevents death in coxsackievirus B3 induced murine myocarditis through
      inhibition of virus attachment and penetration.
AB  - Viral myocarditis affects about 5% to 20% of the population. So far, there are
      not many effective antiviral treatments available. QiHong, the combination of the
      extracts from Astragali (Huangqi), Rhadiola rosea (Hongjingtian), and Sophora
      flavescens (Kushen), was developed based on laboratory research. The aim of this
      study was to investigate the effect and mechanism of QiHong on coxsackievirus B3
      (CVB3)-induced myocarditis. The antiviral activity of QiHong in vitro was
      evaluated on HeLa and Vero cells infected by CVB3. Ribavirin was chosen as
      positive control. Our results showed that QiHong possessed potent antiviral
      effects on CVB3 by sodium 3'-[1-(phenylamino-carbonyl)-3, 4-tetrazolium]-bis (4
      methoxy-6-nitro) benzene sulfonic acid and plaque-forming assay (50% inhibitory
      concentrations [IC50] were 7.16 +/- 0.8 microg/ml and 2.63 +/- 0.5 microg/ml,
      respectively). The 50% cytotoxicity concentration (CC50) was 16-fold higher in
      QiHong-treated cells than in ribavirin-treated cells. Time course studies
      demonstrated that the antiviral effect of QiHong was mainly found during 0-4 hrs
      of infection, and it blocked the attachment and penetration of CVB3 into cells.
      In vivo 4-week-old male Balb/C mice were used and inoculated intraperitoneally
      with CVB3 suspension or normal saline. At 48 hrs after inoculation, the infected
      mice were gavaged with QiHong or ribavirin. On Day 6, myocardial virus titers
      were significantly lower in the QiHong-treated group than in the viral-infected
      groups. On Day 14, QiHong significantly ameliorated CVB3-induced myocardium
      necrosis; on Day 28, QiHong treatment increased survival rate 4-fold compared
      with CVB3-infected controls (64% vs. 16%; P < 0.05). The results showed that
      QiHong is a very promising potent antiviral agent with a highly significant
      favorable effect on survival and pathologic changes in CVB3-induced myocarditis
      with less toxicity than ribavirin. The antiviral activity of QiHong is at least
      partially due to an inhibitory effect on virus attachment and penetration.

PMID- 18040069
TI  - Fundectomy-evoked osteopenia in pigs is mediated by the gastric-hypothalamic
      pituitary axis.
AB  - The aim of the study was to determine the effects of gastric impairment in pigs
      on the axial and peripheral skeletal system properties and to test the hypothesis
      that fundectomy-evoked osteopenia is related to disturbed gastric-hypothalamic
      pituitary axis function. Forty-day-old male piglets were subjected to
      experimental fundectomy (FX group, n = 6) to induce osteopenia, while sham
      operation was performed in the controls (SHO group, n = 6). At the age of 8
      months, serum samples were collected, and the animals were sacrificed to obtain
      lumbar vertebrae (L1-L6) and right humerus for analysis. Using quantitative
      computed tomography (QCT) and dual-energy x-ray absorptiometry (DEXA) methods,
      bone mineral density and bone mineral content of the vertebrae and humerus were
      measured. The compression and three-point bending tests were applied to determine
      mechanical properties of lumbar vertebrae and humerus, respectively. Furthermore,
      geometric properties of humerus were assessed. Serum concentrations of ghrelin,
      growth hormone (GH), insulin-like growth factor-1 (IGF-1), and selected macro-
      and microelements were also determined. Performed fundectomy decreased body
      weight in pigs by 66% compared with pair-fed sham operated pigs (P < 0.0001).
      Bone weight, bone mineral density, and bone mineral content of the lumbar
      vertebrae and humerus were significantly decreased in the fundectomized pigs (P <
      0.01). Mechanical parameters of the lumbar spine and humerus were decreased after
      the fundectomy, as well. Serum concentrations of ghrelin, GH, and IGF-1 were
      lowered by 74.4%, 90.6%, and 54.6% in the fundectomized pigs, respectively (all P
      < 0.001). Moreover, the serum concentrations of calcium, magnesium, iron and
      copper in the fundectomized animals were significantly decreased by 15.5%, 45.3%,
      26.7%, and 26.2%, respectively (P <or= 0.05). In conclusion, the results obtained
      showed that both the disturbed gastric-hypothalamic-pituitary axis function and
      impaired mineral metabolism are associated with development of postfundectomy
      osteopenia of axial and peripheral skeleton in pigs.

PMID- 18040070
TI  - Nitric oxide bioavailability and not production is first altered during the onset
      of insulin resistance in sucrose-fed rats.
AB  - Although the role of nitric oxide (NO) in peripheral glucose uptake has been
      thoroughly described, little is known regarding the alterations in NO metabolism
      during the early onset of insulin resistance. During this study we investigated
      the alterations in NO synthesis and bioavailability in a model for dietary
      modulations of insulin sensitivity. For 6 weeks, rats were fed a standard diet
      (C), a high-sucrose diet inducing insulin resistance (HS), or high-sucrose diets
      supplemented with cysteine, which endowed protection against the high-sucrose
      induced insulin resistance (Ti). Several markers of NO synthesis and
      bioavailability were assessed and confronted with markers of insulin sensitivity.
      After 5 weeks, although urinary cGMP excretion did not differ between the groups,
      insulin resistance in HS rats was associated with both a significant increase in
      NO oxidation, as determined by plasma nitrotyrosine concentrations, and in the
      inducible NO synthase (iNOS)/endothelial NO synthase (iNOS/eNOS) mRNA ratio in
      skeletal muscle compared with C rats. These alterations were prevented in rats
      fed the cysteine-rich diets. NO production, as assessed by urinary 15NO3*
      excretion following a [15N2-(guanido)]-arginine intra-venous bolus, independently
      and significantly correlated with insulin sensitivity but did not significantly
      differ between C, HS, and Ti rats; neither did the aortic eNOS protein expression
      or skeletal muscle insulin-induced eNOS activation. Our results indicate that in
      this model of dietary modulations of insulin sensitivity (i) NO production
      accounts for part of total inter-individual variation in insulin sensitivity, but
      (ii) early diet-related changes in insulin sensitivity are accompanied by changes
      in NO bioavailability.

PMID- 18040071
TI  - Age and species dependence of pial arteriolar responses to topical carbon
      monoxide in vivo.
AB  - In newborn pigs, carbon monoxide (CO) contributes to regulation of
      cerebrovascular circulation. Results from isolated adult cerebral arteries
      suggest CO may have less dilatory potential in mature animals. However, few data
      are available on the direct effects of CO on cerebrovascular circulation in vivo
      except for those from newborn pigs. Therefore, we tested the hypothesis that i)
      rat cerebral arterioles dilate to CO in vivo and ii) CO-induced cerebrovascular
      dilatory responses are age dependent in pigs. Also, we examined whether the
      permissive role of nitric oxide in CO-induced dilation observed in piglets is
      present in older pigs and rats. Experiments used anesthetized newborn, 7-week
      old, and juvenile (3- to 4-month-old) pigs and 3- to 4-month-old rats with closed
      cranial windows and topical applications of CO and sodium nitroprusside (SNP).
      Dilations to SNP were not different at different ages in pigs or between pigs and
      rats. CO produced pial arteriolar dilations in all groups. Dilation to 10(-5) M
      CO was reduced in juvenile pigs as compared to newborn and 7-week-old pigs, and
      tended to less at 10(-6) M CO. Dilations of rat pial arterioles to all
      concentrations were less than those of newborn and 7-week-old pigs, but not
      different from those of juvenile pig pial arterioles. In newborn and 7-week-old
      pigs, l-nitro-arginine (LNA) inhibited the dilation to CO, an effect reversed by
      a constant background of SNP. In contrast, LNA did not reduce dilation to CO in
      juvenile pigs or rats. In conclusion, rat pial arterioles like those in piglets
      dilate to CO in vivo, but there are age and species differences with regard to
      reactivity and interaction with NO.

PMID- 18040072
TI  - The isolation of reticulocyte-free human red blood cells.
AB  - We depleted reticulocytes from erythrocytes of both sickle cell disease (SCD)
      subjects and healthy controls by four methods: fluorescence-activated cell
      sorting (FACS), Miltenyi immunomagnetic depletion (MACS), a combination of these
      methods (FACS + MACS) and Percoll density separation. The efficiency of these
      methods was assessed by new methylene blue staining and manual enumeration of the
      reticulocytes. FACS sorted erythrocytes from reticulocytes based on size and
      granularity, as well as the absence of dsDNA staining. MACS depleted
      reticulocytes from erythrocytes based on the immunoaffinity to CD36 and CD71.
      Reticulocytes from healthy controls were depleted to <or=0.1% using either the
      FACS or MACS method (alpha = 0.1). Reticulocytes from SCD subjects were depleted
      from 13.6% +/- 0.52% to 5.45% +/- 0.33% using MACS (n = 2), and from 10.9% +/-
      0.47% to 2.0% +/- 0.2% using FACS (n = 4, alpha = 0.05). When combining FACS with
      MACS (n=3), the percentage of reticulocytes was decreased in SCD samples from
      13.0% +/- 0.51% down to 1.5% +/- 0.17% (alpha = 0.1). Sedimentation through 75%
      percoll resulted in control and SCD samples being reduced from 0.27% +/- 0.6
      (control) and 6.93% +/- 0.8 (SCD) reticulocytes to < 4.8 reticulocytes per
      million control RBCs and <2.5 per million SCD RBCs. This same method results in
      <2.1 leukocytes per million control RBCs and <3.7 per million SCD RBCs. We
      conclude that the percoll density method described here is the most effective
      method for isolating RBCs for proteomic analysis.

PMID- 18040073
TI  - Nonviral vector-based gene transfection of primary human skeletal myoblasts.
AB  - Low-level transgene efficiency is one of the main obstacles in ex vivo nonviral
      vector-mediated gene transfer into primary human skeletal myoblasts (hSkMs). We
      optimized the cholesterol:N-[1-(2, 3-dioleoyloxy)propyl]-N, N, N
      trimethylammonium methylsulfate liposome (CD liposome) and 22-kDa
      polyethylenimine (PEI22)- and 25-kDa polyethylenimine (PEI25)-mediated
      transfection of primary hSkMs for angiogenic gene delivery. We found that
      transfection efficiency and cell viability of three nonviral vectors were cell
      passage dependent: early cell passages of hSkMs had higher transfection
      efficiencies with poor cell viabilities, whereas later cell passages of hSkMs had
      lower transfection efficiencies with better cell viabilities. Trypsinization
      improved the transfection efficiency by 20% to 60% compared with adherent hSkMs.
      Optimum gene transfection efficiency was found with passage 6 trypsinized hSkMs:
      transfection efficiency with CD lipoplexes was 6.99 +/- 0.13%, PEI22 polyplexes
      was 18.58 +/- 1.57%, and PEI25 polyplexes was 13.32 +/- 0.88%. When pEGFP (a
      plasmid encoding the enhanced green fluorescent protein) was replaced with a
      vector containing human vascular endothelial growth factor 165 (phVEGF(165)), the
      optimized gene transfection conditions resulted in hVEGF(165) expression up to
      Day 18 with a peak level at Day 2 after transfection. This study demonstrated
      that therapeutic angiogenic gene transfer through CD or PEI is feasible and safe
      after optimization. It could be a potential strategy for treatment of ischemic
      disease for angiomyogenesis.

PMID- 18040074
TI  - Immunolocalization of Periostin-like factor and Periostin during embryogenesis.
AB  - Periostin-like factor (PLF) and Periostin are alternatively spliced mRNAs. Our
      findings are the first to show similarities and differences between PLF and
      Periostin location using isoform-specific antibodies. The differences in when and
      where they are present during mouse embryogenesis suggest that they may have
      different functions. Using immunostaining techniques, we observed that PLF was
      highly expressed at 12.5 days postconception (dpc) in the intermediate and outer
      zones of most brain regions, spinal cord, cranial and spinal nerves, and
      chondrocytes in developing bone and in the heart wall. By 16.5 dpc, PLF was also
      present in ameloblasts and odontoblasts in developing teeth, and by 19.5 dpc, PLF
      was present at low levels only in vagal nerve bundles, discrete white matter
      bundles in the brain, and chondrocytes of developing ribs. Periostin, on the
      other hand, was absent at 12.5 dpc from dorsal spinal cord and from cranial and
      spinal nerves. By 16.5 dpc, Periostin was present in many spinal nerves, but
      absent thereafter, and at 19.5 dpc, Periostin was present in chondrocytes in
      developing bone but not in neural tissues. The different spatial and temporal
      location of PLF and Periostin in cartilage and bone cells suggests different
      roles for these proteins in endochondral bone formation. The early expression of
      PLF in brain differentiation zones and in developing axon bundles and nerves
      suggests that it may facilitate axon growth.

PMID- 18040075
TI  - Immunolocalization of a novel collectin CL-K1 in murine tissues.
AB  - We have recently identified a novel collectin, CL-K1, that may play a role in
      innate immunity as a member of the collectin family. In this study using mice, we
      investigated the tissue distribution of CL-K1 for better understanding of its
      pathophysiological relevance. Real-time PCR analyses demonstrated that CL-K1 mRNA
      was expressed in all tissues tested. Immunohistochemical analyses demonstrated
      that CL-K1 was expressed in proximal tubules of kidney, in mucosa of the
      gastrointestinal tract, and in bronchial glands of bronchioles similar to the
      localization of SP-A and SP-D in these pulmonary structures. Immunohistochemistry
      also showed that CL-K1 was highly expressed in hepatocytes around the central
      veins in liver, which suggests that murine CL-K1 may be mainly produced in the
      liver and secreted into the blood stream as is human CL-K1. CL-K1 was especially
      detected in vascular smooth muscle in several types of tissues. In addition, it
      was also expressed in intestinal Paneth cells, in mesangial cells of kidney, in
      pancreatic islet D cells, and in neurons of the brain. It is of interest that
      this profile of CL-K1 expression is unique among the collectins. Together these
      histological findings may be useful for understanding the biological function of
      this novel collectin.

PMID- 18040076
TI  - Immunohistochemical localization of collagen type XI alpha1 and alpha2 chains in
      human colon tissue.
AB  - In previous studies, collagen XI mRNA has been detected in colon cancer, but its
      location in human colon tissue has not been determined. The heterotrimeric
      collagen XI consists of three alpha chains. While it is known that collagen XI
      plays a regulatory role in collagen fibril formation, its function in the colon
      is unknown. The characterization of normal human colon tissue will allow a better
      understanding of the variance of collagen XI in abnormal tissues. Grossly normal
      and malignant human colon tissue was obtained from pathology archives.
      Immunohistochemical staining with a 58K Golgi marker and alpha1(XI) and
      alpha2(XI) antisera was used to specifically locate their presence in normal
      colon tissue. A comparative bright field microscopic analysis showed the presence
      of collagen XI in human colon. The juxtanuclear, dot-like collagen XI staining in
      the Golgi apparatus of goblet cells in normal tissue paralleled the staining of
      the 58K Golgi marker. Ultra light microscopy verified these results. Staining was
      also confirmed in malignant colon tissue. This study is the first to show that
      collagen XI is present in the Golgi apparatus of normal human colon goblet cells
      and localizes collagen XI in both normal and malignant tissue. Although the
      function of collagen XI in the colon is unknown, our immunohistochemical
      characterization provides the foundation for future immunohistopathology studies
      of the colon.

PMID- 18040077
TI  - Dendritic cell populations in colon and mesenteric lymph nodes of patients with
      Crohn's disease.
AB  - Dendritic cells (DCs) are key cells in innate and adaptive immune responses that
      determine the pathophysiology of Crohn's disease. Intestinal DCs migrate from the
      mucosa into mesenteric lymph nodes (MLNs). A number of different markers are
      described to define the DC populations. In this study we have identified the
      phenotype and localization of intestinal and MLN DCs in patients with Crohn's
      disease and non-IBD patients based on these markers. We used immunohistochemistry
      to demonstrate that all markers (S-100, CD83, DC-SIGN, BDCA1-4, and CD1a) showed
      a different staining pattern varying from localization in T-cell areas of lymph
      follicles around blood vessels or single cells in the lamina propria and in the
      MLN in the medullary cords and in the subcapsular sinuses around blood vessels
      and in the T-cell areas. In conclusion, all different DC markers give variable
      staining patterns so there is no marker for the DC.

PMID- 18040078
TI  - Expression of Toll-like receptor 2 (TLR2), TLR4, and CD14 in biopsy samples of
      patients with inflammatory bowel diseases: upregulated expression of TLR2 in
      terminal ileum of patients with ulcerative colitis.
AB  - Dysregulation of innate and adaptive intestinal immune responses to bacterial
      microbiota is supposed to be involved in pathogenetic mechanisms of inflammatory
      bowel diseases (IBDs). We investigated expression of Toll-like receptor 2 (TLR2),
      TLR4, and their transmembrane coreceptor CD14 in biopsy samples from patients
      with IBD and in non-inflamed gut mucosa from controls. Small intestine and colon
      samples were obtained by colonoscopy from patients with Crohn's disease (CD),
      ulcerative colitis (UC), and controls. Immunohistochemical analysis of cryostat
      sections using polyclonal and monoclonal antibodies specific for TLR2, TLR4, and
      CD14 showed a significant increase in TLR2 expression in the terminal ileum of
      patients with inactive and active UC against controls. Significant upregulation
      of TLR4 expression relative to controls was found in the terminal ileum and
      rectum of UC patients in remission and in the terminal ileum of CD patients with
      active disease. CD14 expression was upregulated in the terminal ileum of CD
      patients in remission and with active disease, in the cecum of UC patients in
      remission and with active disease, and in rectum of UC patients with active
      disease. Hence, dysregulation of TLR2, TLR4, and CD14 expression in different
      parts of the intestinal mucosa may be crucial in IBD pathogenesis.

PMID- 18040079
TI  - Immunogold electron microscopic demonstration of distinct submembranous
      localization of the activated gammaPKC depending on the stimulation.
AB  - We examined the precise intracellular translocation of gamma subtype of protein
      kinase C (gammaPKC) after various extracellular stimuli using confocal laser
      scanning fluorescent microscopy (CLSM) and immunogold electron microscopy. By
      CLSM, treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a
      slow and irreversible accumulation of green fluorescent protein (GFP)-tagged
      gammaPKC (gammaPKC-GFP) on the plasma membrane. In contrast, treatment with
      Ca(2+) ionophore and activation of purinergic or NMDA receptors induced a rapid
      and transient membrane translocation of gammaPKC-GFP. Although each stimulus
      resulted in PKC localization at the plasma membrane, electron microscopy revealed
      that gammaPKC showed a subtle but significantly different localization depending
      on stimulation. Whereas TPA and UTP induced a sustained localization of gammaPKC
      GFP on the plasma membrane, Ca(2+) ionophore and NMDA rapidly translocated
      gammaPKC-GFP to the plasma membrane and then restricted gammaPKC-GFP in
      submembranous area (<500 nm from the plasma membrane). These results suggest that
      Ca(2+) influx alone induced the association of gammaPKC with the plasma membrane
      for only a moment and then located this enzyme at a proper distance in a touch
      and-go manner, whereas diacylglycerol or TPA tightly anchored this enzyme on the
      plasma membrane. The distinct subcellular targeting of gammaPKC in response to
      various stimuli suggests a novel mechanism for PKC activation.

PMID- 18040080
TI  - NG2 proteoglycan expression in mouse skin: altered postnatal skin development in
      the NG2 null mouse.
AB  - In early postnatal mouse skin, the NG2 proteoglycan is expressed in the subcutis,
      the dermis, the outer root sheath of hair follicles, and the basal keratinocyte
      layer of the epidermis. With further development, NG2 is most prominently
      expressed by stem cells in the hair follicle bulge region, as also observed in
      adult human skin. During telogen and anagen phases of the adult hair cycle, NG2
      is also found in stem cell populations that reside in dermal papillae and the
      outer root sheaths of hair follicles. Ablation of NG2 produces alterations in
      both the epidermis and subcutis layers of neonatal skin. Compared with wild type,
      the NG2 null epidermis does not achieve its full thickness due to reduced
      proliferation of basal keratinocytes that serve as the stem cell population in
      this layer. Thickening of the subcutis is also delayed in NG2 null skin due to
      deficiencies in the adipocyte population.

PMID- 18040081
TI  - Immunocytochemistry and laser capture microdissection for real-time quantitative
      PCR identify hindbrain neurons activated by interaction between leptin and
      cholecystokinin.
AB  - Current evidence suggests that leptin reduces food intake in part by enhancing
      the hindbrain neuronal response to meal-related gastrointestinal signals,
      including cholecystokinin (CCK), but the phenotypes of the relevant cells are not
      known. To identify neurons that participate in this interaction in the rat
      nucleus of the solitary tract (NTS), we induced c-Fos gene expression in NTS
      neurons with leptin and CCK. We focused on NTS catecholamine neurons because
      these cells have been implicated in the feeding response to CCK. Hindbrain
      sections from rats that received CCK with or without leptin pretreatment were
      immunostained for c-Fos and tyrosine hydroxylase (TH) by a double
      immunofluorescence procedure. Leptin pretreatment increased the number of NTS
      cells expressing c-Fos-like immunoreactivity (cFLI) 3-fold relative to CCK alone,
      but the number of TH-positive cells with cFLI was increased 6-fold. Next, cells
      detected by immunofluorescence for TH were collected by laser capture
      microdissection and pooled for real-time quantitative PCR of c-Fos mRNA. Here,
      neither le0ptin nor CCK alone affected the relative amount of mRNA in the TH cell
      enriched samples, but leptin plus CCK substantially increased c-Fos mRNA content.
      These histochemical findings identify hindbrain catecholamine cells as potential
      mediators of the interaction between leptin and CCK.

PMID- 18040082
TI  - Endocannabinoids, cannabinoid receptors and inflammatory stress: an interview
      with Dr. Pal [corrected] Pacher. Interviewed by Helene F. Rosenberg.

PMID- 18040083
TI  - Mycobacterium bovis BCG disrupts the interaction of Rab7 with RILP contributing
      to inhibition of phagosome maturation.
AB  - Phagosomes containing M. tuberculosis and M. bovis BCG interact normally with
      early endosomes but fail to fuse with late endosomes and lysosomes. Whereas many
      early events of mycobacterial phagosomes have been elucidated, the exact
      mechanism of the inhibition of fusion with lysosomes is still unclear. Several
      Rab GTPase proteins were shown to be involved in membrane fusion and vesicular
      transport. In particular, Rab7 associates with the phagosomal membrane and
      regulates the fusion between late endosomes and lysosomes. This function of Rab7
      was shown to be mediated in epithelial cell models by the Rab7 effector RILP
      (Rab7-interacting lysosomal protein). However, the relevance of Rab7-RILP
      interaction to phagosome biogenesis in macrophage infected with mycobacteria is
      still unknown. In this study, cotransfection of RAW 264.7 cells with Rab7 and
      RILP revealed that Rab7-RILP interaction occurs in macrophages ingesting latex
      beads. Thereafter, this cell system model was used to demonstrate that infection
      with live but not killed M. bovis BCG inhibited RILP recruitment despite Rab7
      acquisition by the phagosome. Further investigation using immobilized RILP to
      pull down active Rab7 (GTP-bound form) from macrophage lysates demonstrated that
      inactive Rab7 (GDP-bound form) predominates in cells infected with live BCG. In
      addition, cell-free system experiments demonstrated that BCG culture supernatant
      contains a factor that catalyzes the GTP/GDP switch on recombinant Rab7
      molecules. Such a factor was shown to diffuse beyond BCG phagosomes and target
      other Rab7-positive compartments. These findings suggest that live mycobacteria
      express within the macrophage a Rab7 deactivating factor leading to abortion of
      RILP-mediated fusion with lysosomes.

PMID- 18040084
TI  - Accelerated wound healing in leukocyte-specific, protein 1-deficient mouse is
      associated with increased infiltration of leukocytes and fibrocytes.
AB  - Wound healing is a complex process involving the integrated actions of numerous
      cell types, soluble mediators, and ECM. Recently, a newly identified cell type,
      the fibrocyte, has been reported to contribute to wound healing and fibrotic
      conditions such as hypertrophic scarring. We previously established leukocyte
      specific protein 1 (LSP1) as a marker for fibrocytes. LSP1 is an F-actin binding
      protein and substrate of p38 mitogen-activated protein kinase and protein kinase
      C, and has been reported to be important in leukocyte chemotaxis. We examine the
      biological roles of LSP1 in skin wound healing using Lsp1(-/-) null mice. These
      animals showed accelerated healing of full-thickness skin wounds, with increased
      re-epithelialization rates, collagen synthesis, and angiogenesis. Healing wounds
      in Lsp1(-/-) mice had higher densities of neutrophiles, macrophages, and
      fibrocytes. Along with increased leukocyte infiltration, levels of macrophage
      derived chemokine expression, TGF-beta1, and VEGF were all up-regulated. These
      results demonstrate that the absence of LSP1 promotes healing of skin wounds. The
      primary mechanism seems to be an increase in leukocyte infiltration, leading to
      locally elevated synthesis and release of chemokines and growth factors. Further
      analysis of Lsp1(-/-) mice may suggest ways to improve wound healing and/or treat
      fibrotic conditions of skin and other tissue.

PMID- 18040087
TI  - Somatic presentations of mental disorders: refining the research agenda for DSM
      V.

PMID- 18040089
TI  - Evolution of psychosomatic diagnosis in DSM.

PMID- 18040090
TI  - Cultural models and somatic syndromes.
AB  - OBJECTIVES: To review the relevance of cultural models in the generation and
      amplification of somatic symptoms and syndromes. METHODS: Based on a selective
      review of literature, we examine evidence that cultural and personal explanatory
      models can contribute to the pathogenesis, symptomatology, and chronicity of
      medically unexplained symptoms and functional somatic syndromes. RESULTS: In the
      contemporary world, culture involves flows of information, roles, and
      institutions that offer individuals multiple models for understanding illness.
      Cultural models include 1) explanatory models, which make causal attributions and
      impute specific mechanisms or processes of pathophysiology; 2) prototypes, which
      are salient images or exemplars drawn from personal experience, family, friends,
      mass media, and popular culture that are used to reason analogically about one's
      own condition; and 3) implicit models and procedural knowledge that may be
      difficult to articulate because they are embedded in body practices and ways of
      experiencing distress. Symptom attributions and explanations can participate in
      vicious circles of symptom amplification that give rise to culture-specific
      varieties of panic disorder, hypochondriacal worry, and medically unexplained
      symptoms. CONCLUSIONS: Clinical research using the methods of experimental
      cognitive and social psychology as well as community-based ethnographic and
      ecological research are needed to advance our understanding of the impact of
      personal and cultural models on somatic distress. Nevertheless, the current state
      of knowledge on social and cultural dimensions of somatic syndromes suggests a
      typology of forms of psychosomatic and sociosomatic looping that has implications
      for the nosology of somatoform disorders.

PMID- 18040091
TI  - Influence of cultural and social factors on the epidemiology of idiopathic
      somatic complaints and syndromes.
AB  - OBJECTIVE: To review international research on somatic presentations often seen
      together with or attributed to psychopathology. For conceptual clarity, we refer
      to these presentations as "idiopathic somatic complaints and syndromes" (ISCS).
      This review will also pose specific questions on cultural issues affecting these
      somatic manifestations. METHOD: Selective review of the international literature
      dealing with the phenomenology, epidemiology, and cultural profile of ISCS
      focusing on papers published in refereed journals and written in English.
      RESULTS: Major problems with much of the previous research in this area are the
      use of different definitions and ascertainment procedures. As currently
      conceptualized in the literature, ISCS are universal and seem closely related to
      psychological issues (stress) and psychopathological conditions such as
      depression worldwide. Although there are many similarities regarding the form and
      content of these somatic presentations across cultures, there is some evidence
      for cultural patterning of symptoms. Unfortunately, current classifications for
      ISCS are unsatisfactory. CONCLUSIONS: We outline specific recommendations for
      conducting future research and for improving the classification of ISCS of
      presumed psychological origin or import in future nosologies.

PMID- 18040092
TI  - Are somatoform disorders changing with time? The case of neurasthenia in China.
AB  - OBJECTIVE: To examine how sociocultural factors shape the professional
      classification and transformation of neurasthenia (shenjing shuairuo in the
      Chinese language) in China. METHODS: We review the relevant literature as well as
      cite our own research experience on the topic. RESULTS: We identify three main
      periods of transformation, namely, the prereform period (before 1980) in which
      neurasthenia encompassed a wide range of anxiety and mood disorders; the reform
      period (1980s-1995) when the Diagnostic and Statistical Manual of Mental
      Disorders-III (DSM-III) and Kleinman's study in Hunan steadily shaped the Chinese
      conceptualization of nonpsychotic mental disorders; and the postreform period
      (after 1995) when neurasthenia has become a rarely used category of subsyndromal
      depression among Chinese psychiatrists. CONCLUSIONS: The dramatic transformation
      of neurasthenia in China speaks to the global power of the DSM system of
      classification, on the one hand, and the latter's failure to engage cultures in
      the local system of psychiatric practice, on the other. The Chinese story of
      neurasthenia and the social context in which the disease category is contested,
      marginalized, and reconstituted as the popular Western disease of depression
      among Chinese psychiatrists attest to the socially constructed nature of
      psychiatric classification. The public health implications of this transformation
      remain unclear.

PMID- 18040093
TI  - A biological substrate for somatoform disorders: importance of pathophysiology.
AB  - Somatoform disorders are troubling to both patients and physicians. The diagnosis
      regrettably relies on the presence of subjective distress in the absence of
      objective findings. As a result, there is always the possibility that a diagnosis
      will be "missed." There is a clear underlying physiology of distress, which
      implies that there is a two-way street--both psychosomatic and somatopsychic in
      terms of production and experience of somatoform symptoms. Studies on
      communication pathways from the immune system to the brain provide exciting new
      information on the pathophysiology of inflammation-associated symptoms.

PMID- 18040095
TI  - Epidemiology of the association between somatoform disorders and anxiety and
      depressive disorders: an update.
AB  - OBJECTIVE: To review the available epidemiological evidence on associations
      between somatoform disorders with anxiety and depressive disorders. RESULTS:
      Clinical and population-based studies have found that the co-occurrence of some
      types of somatoform disorders (e.g., somatization disorder, somatic-symptom-index
      (SSI)4,6, and pain disorder) and anxiety and depressive disorders is common.
      These findings may suggest either a causal relationship between these disorders
      or that they share some common etiological factors. For other forms of somatoform
      disorders, empirical evidence about co-occurrence is even thinner or not
      available at all, especially from non-western settings. CONCLUSION: Some
      implications of how these findings, or the absence of them, can help us
      understand better the etiology of somatoform disorders and improve the
      classification of mental disorders as a whole are discussed.

PMID- 18040094
TI  - The association or otherwise of the functional somatic syndromes.
AB  - OBJECTIVE: To review the evidence for overlap in the phenomenology of the
      Functional Somatic Syndromes (FSS). The FSS show considerable comorbidity,
      leading some to suggest they may be aspects of the same disorder. METHODS: We
      conducted a selective review of peer-reviewed articles on the co-occurrence of
      FSS symptoms and diagnoses. RESULTS: Considerable evidence of overlap was found
      at the level of symptoms, diagnostic criteria, and clinical diagnoses made.
      CONCLUSIONS: Phenomenological commonalities support a close relationship between
      the FSS, although differences remain in other domains. Whether the FSS may best
      be considered the same or different will depend on the pragmatics of diagnosis.

PMID- 18040096
TI  - Stability of somatoform symptoms--implications for classification.
AB  - OBJECTIVE: To investigate the stability of somatoform symptoms/disorders.
      METHODS: A literature search was done to select studies reporting data on
      stability of medically unexplained physical symptoms. RESULTS: Whereas individual
      symptoms vary over time, grouping symptoms into syndromes seems to create stable
      features. There are substantial problems with the use of lifetime diagnosis,
      favoring classification approaches that require only present state symptoms.
      Further, doctors' ratings that symptoms are "medically unexplained" is highly
      problematic and reduces interrater reliability. Misdiagnoses and overlooking of
      organic conditions are in the same range as for other psychiatric (and many
      organic) disorders; therefore, this does not seem to reduce the stability of the
      diagnoses of somatoform disorders. CONCLUSIONS: These results indicate how the
      classification of somatoform disorders can be improved. Some new diagnostic
      criteria are suggested that could be considered in the revision of Diagnostic and
      Statistical Manual of Mental Disorders-V (DSM-V).

PMID- 18040097
TI  - Somatoform and substance use disorders.
AB  - OBJECTIVE: To review the potential for diagnostic difficulties and overlap in a
      number of symptoms of somatoform disorders and symptoms of withdrawal from
      alcohol and drugs, and to review epidemiologic, family, and clinical studies
      addressing comorbidity between somatoform and substance use disorders. The
      comorbidity between somatoform disorders and substance use disorders has rarely
      been studied. METHODS: Symptoms of somatoform disorders and substance withdrawal
      were compared. A PubMed-based literature review was conducted. RESULTS:
      Somatoform and withdrawal symptoms overlap considerably. Few studies, however,
      have addressed comorbidity between somatoform and substance use disorders.
      Although results are inconsistent, a number of studies suggest that an
      association exists. CONCLUSION: More research on this type of comorbidity is
      warranted because the associations may be stronger than generally assumed. Such
      research should address methodological problems to produce studies with clearer
      findings.

PMID- 18040098
TI  - Are treatments for common mental disorders also effective for functional symptoms
      and disorder?
AB  - OBJECTIVE: To consider whether the many types of treatments for mental disorders-
      both those specifically targeting illness mechanisms and nonspecific elements-
      are also effective in treating functional symptoms and syndromes. The paper
      discusses the need for well-organized care that emphasizes early treatment and
      recognition of more complex problems in primary and secondary medical care.
      METHODS: Evidence from a wide range of research and clinical experience is used
      to identify and illustrate general themes. RESULTS: Despite a limited evidence
      base, it is clear that both specific and nonspecific interventions that are
      effective with mental disorders are also effective in treating functional
      complaints. They are also helpful in the management of maladaptive reactions to
      physical disorders. Delivery is most effective as stepped care. CONCLUSIONS:
      There is a particular need for more evidence on the effectiveness of the
      nonspecific elements of treatment and of their most appropriate delivery by
      nonspecialists in general medical settings. Experience with a variety of
      treatment methods will enhance our understanding of psychological and other
      etiological variables and thereby influence the development of improved
      definitions in Diagnostic and Statistical Manual of Mental Disorders-5(th)
      Edition. It is argued that a main focus of review of somatoform disorder should
      be the resolution of conceptual problems.

PMID- 18040099
TI  - Efficacy of treatment for somatoform disorders: a review of randomized controlled
      trials.
AB  - OBJECTIVE: To review the evidence from randomized clinical trials (RCTs) that
      have focused on the treatment of patients with Diagnostic and Statistical Manual
      of Mental Disorders, 4(th) Edition (DSM-IV) somatoform disorders. Although
      somatoform disorders are among the most common mental disorders presenting in the
      general medical setting, the strength of evidence for specific treatments has not
      been well synthesized. METHODS: MEDLINE search of articles published in English
      from 1966 to 2006, using the following search terms: randomized clinical trial,
      somatoform disorders, somatization disorder, undifferentiated somatoform
      disorder, hypochrondriasis, conversion disorder, pain disorder, and body
      dysmorphic disorder. RESULTS: A total of 34 RCTs involving 3922 patients were
      included. Two thirds of the studies involved somatization disorder (n = 4
      studies) and lower threshold variants, such as abridged somatization disorder (n
      = 9) and medically unexplained symptoms (n = 10). Cognitive behavioral therapy
      (CBT) was effective in most studies (11 of 13), as were antidepressants in a
      small number (4 of 5) of studies. RCTs examining a variety of other treatments
      showed benefit in half (8 of 16) of the studies, the most consistent evidence
      existing for a consultation letter to the primary care physician. Effective
      treatments have been established for all somatoform disorders except conversion
      disorder (1 of 3 studies showing benefit) and pain disorder (no studies
      reported). CONCLUSION: CBT is the best established treatment for a variety of
      somatoform disorders, with some benefit also demonstrated for a consultation
      letter to the primary care physician. Preliminary but not yet conclusive evidence
      exists for antidepressants.

PMID- 18040100
TI  - What is the evidence for the efficacy of treatments for somatoform disorders? A
      critical review of previous intervention studies.
AB  - OBJECTIVE: To review published literature for the highest level of evidence on
      the efficacy of treatment for patients with medically unexplained symptoms.
      METHODS: A comprehensive literature search was carried out in Cochrane library,
      Medline (1971-2007), PsychINFO (1974-2006), and EMBASE (1980-2007) to identify
      pharmacological, nonpharmacological, psychological, and other interventions,
      using the search terms "medically unexplained symptoms," "somatisation,"
      "somatization," "somatoform disorders," "psychological therapies," "cognitive
      behavior therapy," "pharmacological therapies," "management," "therapy," "drug
      therapy," and "anti-depressants" with Boolean operators AND and OR on the entire
      text. Searches were confined to literature in English. RESULTS: Studies were
      carried out in primary, secondary, and tertiary care settings. The therapists
      ranged from medical specialists, psychiatrists, and psychologists to primary care
      physicians. Three types of interventions (antidepressant medication, cognitive
      behavioral therapy (CBT), and other nonspecific interventions) were supported by
      evidence on the efficacy of treatment for patients with medically unexplained
      symptoms. There is more level I evidence for CBT compared with the amount for
      other approaches. There was only one study reported from the developing world.
      CONCLUSIONS: CBT is efficacious for either symptom syndromes or for the broader
      category of medically unexplained symptoms, reducing physical symptoms,
      psychological distress, and disability. A relatively small number of studies were
      carried out in primary care, but the trend has been changing over the last
      decade. No studies have compared pharmacological and psychological treatments.
      Most trials assessed only short-term outcomes. Use of divergent selection
      procedures, interventions, outcome measures, and instruments, and other
      methodological differences observed in these studies hamper the ability to
      compare treatment effects across studies.

PMID- 18040101
TI  - Neuraxial healing.

PMID- 18040102
TI  - Brain cells--recently unveiled secrets: their clinical significance.

PMID- 18040103
TI  - The articles of Babinski on his sign and the paper of 1898.
AB  - In 1896 Joseph Francois Felix Babinski described for the first time the
      phenomenon of the toes; nevertheless in this first paper he simply described
      extension of all toes with pricking of the sole of the foot. It was not until the
      second paper of 1898 that he specifically described the extension of the hallux
      with strong tactile stimulation (stroking) of the lateral border of the sole.
      Babinski probably discovered his sign by a combination of chance observation and
      careful re-observation and replication. He also had in mind practical
      applications of the sign, particularly in the differential diagnosis with
      hysteria and in medico-legal areas. Several of the observations and
      physiopathological mechanisms proposed by Babinski are still valid today, e.g, he
      realized since 1896 that the reflex was part of the flexor reflex synergy and
      observed that several patients during the first hours of an acute cerebral or
      spinal insult had absent extensor responses. He also found that most patients
      with the abnormal reflex had weakness of dorsiflexion of the toes and ankles and
      observed a lack of correlation between hyperactive myotatic reflexes and the
      presence of an upgoing hallux. He discovered that not all patients with
      hemiplegia or paraplegia had the sign but thought erroneously that some normal
      subjects could have an upgoing toe. Between 1896 and 1903 Babinski continued to
      think on the sign that bears his name and enrich its semiological and
      physiopathological value.

PMID- 18040104
TI  - Line bisection performance in right-handed primary headache sufferers.
AB  - CONTEXT: In previous studies, patients with migraine and tension-type headaches
      have shown asymmetries at the central nervous system level. AIMS: Hence we would
      like to figure out whether the lateral cerebral dominance might be more
      pronounced in the line bisection performance with these patients. SETTINGS AND
      DESIGN: Patients were enrolled in a specialized headache clinic and healthy
      volunteers from a community as controls. MATERIALS AND METHODS: The visual line
      bisection is used to test the unilateral neglect of subjects. Altogether, we
      studied 28 patients with chronic tension-type, 16 frequent episodic tension-type
      headache, 31 migraine patients without aura between attacks and 146 healthy
      volunteers. STATISTICAL ANALYSIS: One-way ANOVA was applied to the mean Index and
      Net of line bisection errors and the Spearman rank order to the relationship
      between the Index, Net, subject's age and time since onset of head pain. RESULTS
      AND CONCLUSIONS: As reflected by group means of Index of line bisection errors,
      healthy subjects and migraine patients bisected slightly rightward. Conversely,
      both forms of tension-type headache sufferers bisected significantly leftward
      compared to the healthy subjects as well as the migraine sufferers. The study
      indicates relatively strong right or weak left hemisphere activation or both in
      the two forms of tension-type headaches, confirming the central nervous system
      alterations in such patients.

PMID- 18040106
TI  - Health-related quality of life using QOLIE-31: before and after epilepsy surgery
      a prospective study at a tertiary care center.
AB  - BACKGROUND: Outcome following epilepsy surgery has traditionally been measured in
      terms of relief of seizures. However, changes in health-related quality of life
      (HRQOL) after surgery for intractable epilepsy are also important to document.
      There are no studies on the Indian population which assess the outcome of
      epilepsy surgery in terms of HRQOL. MATERIALS AND METHODS: We conducted a
      prospective study on the patients undergoing epilepsy surgery for intractable
      seizures, between February 2004 and May 2006 at our center. All patients cleared
      for epilepsy surgery by the epilepsy surgery team were taken up for study. All
      patients RESULTS: Thirty-six patients satisfying the inclusion/exclusion criteria
      were included in the analysis. Twenty-nine of these (Group 1) had good seizure
      outcome (Engel 1 and 2), while seven patients (Group 2) had poor seizure outcome
      (Engel 3 and 4) at six months. Overall, 77% of all study patients were completely
      seizure-free at follow-up. There was no baseline difference in the seven domains
      of QOLIE-31 between the two groups. There was very significant improvement (P
      value>0.005 using paired sample T test) in all the domains of QOLIE-31 in the
      good outcome group after surgery. Health-related quality of life improvement was
      seen in all the domains in the poor outcome group also, however, it was
      statistically significant only for the following parameters: seizure worry,
      overall QOL, emotional wellbeing, energy fatigue and social functioning domains.
      Improvement in seizure worry, overall QOL, emotional wellbeing and social
      functioning was significantly more in Group 1 as compared to Group 2. CONCLUSION:
      Complete seizure-free state after surgery is associated with very significant
      improvement in HRQOL parameters. Several, but not all parameters of HRQOL as
      assessed by QOLIE-31, improved after surgery even in the poor seizure outcome
      group. The improvement in domains of seizure worry, overall QOL, emotional
      wellbeing and social functioning is significantly more in those patients in whom
      complete seizure-free state is achieved.

PMID- 18040105
TI  - Gender differences in blood lipids and the risk of ischemic stroke among the
      hypertensive adults in rural China.
AB  - BACKGROUND: Though large epidemiological studies have not established
      associations between blood lipids and ischemic stroke, increasing evidences have
      suggested that lipid-modifying agents may reduce cerebrovascular events. AIMS: To
      determine whether blood lipids are risk factors for ischemic stroke among
      hypertensive rural adults in China. SETTINGS AND DESIGN: A cross-sectional survey
      was conducted during 2004-2006, which underwent cluster multistage sampling to a
      hypertensive resident group in the countryside of China. MATERIALS AND METHODS: A
      total of 6,412 individuals (2,805 men, 3,607 women) with age>or=35 years were
      included. At baseline, lifestyle and other factors were obtained and blood lipids
      were assessed at a central study laboratory. Ischemic stroke was defined
      according to the criteria established by the National Survey of Stroke and all
      cases were further classified into lacunar infarction and other ischemic strokes.
      STATISTICAL ANALYSIS: Univariable and multivariable logistic regression were
      used. RESULTS: In the univariable logistic regression model, LDL cholesterol
      (LDLc) in men and total cholesterol (TC), LDLc and TC-to-HDL cholesterol (TC:
      HDLc ratio) in women were risk factors for other ischemic strokes, with OR 1.42
      (95% CI, 1.16-1.75), 1.31 (95% CI, 1.11-1.55), 1.47 (95% CI, 1.16-1.88) and 1.67
      (95% CI, 1.28-2.14), respectively. After adjusting for independent variables, an
      increase in non-HDL cholesterol (non-HDLc) was associated with a significant
      increased risk of other ischemic strokes in women, with adjusted OR 1.45 (95% CI,
      1.08-1.93). CONCLUSIONS: LDLc was the common risk factor for ischemic stroke in
      men and women, whereas Non-HDLc, TC and TC: HDLc ratio levels were related to
      ischemic stroke as risk factors only in women.

PMID- 18040107
TI  - Intensive care management of head injury patients without routine intracranial
      pressure monitoring.
AB  - BACKGROUND: Head injury contributes significantly to mortality and morbidity in
      India. Evaluation of the available trauma care facilities may help improve
      outcome. AIM: To evaluate the factors influencing the mortality of patients with
      head injury who had intensive care management and evolve strategies to improve
      outcome. SETTING AND DESIGN: Retrospective study in a tertiary hospital where
      intracranial pressure monitoring (ICPM) is not routinely practiced. MATERIALS AND
      METHODS: All patients with head injury managed in the intensive care unit in a
      two-year period were included. The factors evaluated were age, vital signs,
      Glasgow Coma scale score (GCS) at admission, pupillary light reflex (PR),
      oculocephalic reflex (OCR), hemodynamic stability, computerized tomography (CT)
      findings, diabetes mellitus, anemia, infections and abnormalities of serum
      sodium. RESULTS: We analyzed 208 patients (202 without ICPM). In-hospital
      mortality was 64 (31%). Only 24 (11.5%) patients were admitted within one hour of
      injury, while one-third arrived after six hours. The clinical factors (at
      admission) that influenced mortality included age, GCS, PR, OCR and diastolic
      blood pressure (DBP). Effacement of the basal cisterns in the initial and repeat
      CT scans, hyperglycemia, hemodynamic instability and serum sodium imbalances were
      associated with higher mortality. The independent predictors of mortality by
      logistic regression were initial GCS, DBP, hemodynamic instability and effacement
      of cisterns on repeat CT. CONCLUSIONS: Mortality following head injury is high.
      Pre-hospital emergency medical services are disorganized. The key to reducing
      mortality within the limitations of our current trauma system is maintenance of
      DBP>70 mmHg and SBP>90 mmHg from the time of first contact.

PMID- 18040108
TI  - Individualized ventriculostomy in hydrocephalus: an intravital anatomical study.
AB  - BACKGROUND: Ventriculostomy is a common neuroendoscopic operation but one with
      disastrous complications in rare cases. AIMS: The aim of this study was to
      perform an intravital analysis of the configuration at the floor of the third
      ventricle as a possible basis for selection of the ventriculostomy site.
      MATERIALS AND METHODS: The study population consisted of 32 patients who
      underwent ventriculostomy for the treatment of hydrocephalus. Perforation of the
      floor of the third ventricle was carried out on an individual basis following
      evaluation of the anatomic situation. Video material and magnetic resonance
      images (MRI) were analyzed. RESULTS: A classification system including three
      major groups was developed using the inner distance of the mamillary bodies as
      the key criterion. It was defined as narrow for values between 0 and 1 mm
      (observed range: 0-0.5 mm), medium for values between 1.1 and 3.4 mm (range 1.1
      3.4 mm) and large for values greater than 3.4 mm (range: 3.8-6.9 mm). Statistical
      analysis of MR and video measurements revealed a good correlation. The
      ventriculostomy site was rostral of the mamillary bodies in 23 of the patients
      (n=27) and slightly occipital in four. The ventriculostomy site was located more
      to the left in 22 patients and more to the right in five. CONCLUSION: As a
      conclusion the ventriculostomy site has to be chosen in each case following a
      careful review of all available information. A classification system for the
      anatomical variations as well as the exact size and site of ventriculostomy
      should be introduced.

PMID- 18040109
TI  - Occipitocervical contoured rod stabilization: does it still have a role amidst
      the modern stabilization techniques?
AB  - BACKGROUND: The occipitocervical contoured rod (CR) stabilization for use in
      craniovertebral junction (CVJ) pathologies is an effective and economical
      technique of posterior fusion (PF). AIMS: The various indications for CR in CVJ
      pathologies are discussed. SETTINGS AND DESIGN: Retrospective analysis. MATERIALS
      AND METHODS: Fifty-four patients (mean age: 31.02+/-13.44 years; male: female
      ratio=5.75:1) who underwent CR stabilization are included. The majority had
      congenital atlantoaxial dislocation (AAD; n=50); two had CVJ tuberculosis; one
      each had rheumatoid arthritis and C2-3 listhesis, respectively. The indications
      for CR fusion in congenital AAD were associated Chiari 1 malformation (C1M)
      (n=29); occipitalized C1 arch and/or malformed or deficient C1 or C2 posterior
      elements (n=9); hypermobile AAD (n=2); and, rotatory AAD (n=3). Contoured rod as
      a revision procedure was also performed in seven patients. Most patients were in
      poor grade (18 in Grade III [partial dependence for daily needs] and 15 in Grade
      IV [total dependence]); 15 patients were in Grade II [independent except for
      minor deficits] and six in Grade I [no weakness except hyperreflexia or neck
      pain]. RESULTS: Twenty-four patients improved, 18 stabilized and six deteriorated
      at a mean follow-up (FU) of 17.78+/-19.75 (2-84) months. Six patients were lost
      to FU. In 37 patients with a FU of at least three months, stability and bony
      union could be assessed. Thirty-one of them achieved a bony fusion/stable
      construct. CONCLUSIONS: Contoured rod is especially useful for PF in cases of
      congenital AAD with coexisting CIM, cervical scoliosis, sub-axial instability
      and/or asymmetrical facet joints. In acquired pathologies with three-column
      instability, inclusion of joints one level above the affected one by using CR,
      especially enhances stability.

PMID- 18040110
TI  - Validity and reliability of the Persian version of the multiple sclerosis quality
      of life questionnaire.
AB  - BACKGROUND AND AIMS: To translate and test the reliability and validity of the
      Multiple Sclerosis Quality of Life Questionnaire (MSQoL-54) in Iranian MS
      patients. SETTING AND DESIGN: Using a standard "forward-backward" translation,
      cognitive debriefing and cultural adaptation procedure, the English version of
      the MSQoL-54 was translated to Persian which is the Iranian official language.
      MATERIALS AND METHODS: The subjects were multiple sclerosis (MS) patients
      referred to Motaharri clinic, Shiraz, South of Iran. Demographic data were
      recorded. Epidemiological data concerning MS type, duration of the disease,
      Functional System Score (FSS) and Expanded Disability Status Scale (EDSS) of
      patients were also provided by a qualified neurologist. STATISTICAL ANALYSIS: The
      reliability of the questionnaire was assessed by Cronbach's alpha coefficient.
      Construct validity was assessed through factor analysis. Factor analysis was
      performed to determine that the Persian version is a two-dimensional measure
      including physical and mental parameters. RESULTS: Multiple sclerosis patients
      (female:106 (75.2%), male:35 (24.8%)), with a mean+/-SD age of 32.2+/-9.8 years
      were enrolled in the study. Cronbach's alpha was 0.962. There were no significant
      differences between each item and the mean of physical and mental scores of MSQoL
      54, regarding sex, marital status and education. There was a negative significant
      correlation between EDSS and physical health, role limitation due to physical
      problems, pain, energy, health perception, social function, cognitive function,
      health distress, overall Quality of Life. The scaling success rates were 100%,
      demonstrating convergent validity of each scale. Factor analysis confirmed the
      construct validity of the questionnaire. CONCLUSIONS: The Persian version of the
      MSQoL-54 questionnaire has a good structural characteristic, it is a reliable and
      valid instrument and can be used for measuring the effect of MS on the Quality of
      Life.

PMID- 18040111
TI  - Anesthesia for awake craniotomy: a retrospective study.
AB  - CONTEXT: Awake craniotomy is increasingly performed the world over. We share our
      experience of performing craniotomy awake with our anesthetic protocol. AIMS: To
      evaluate and analyze the anesthesia records of the patients who underwent awake
      craniotomy at our institution. SETTINGS AND DESIGN: University teaching hospital,
      Retrospective study. MATERIALS AND METHODS: We reviewed records of the 42
      consecutive patients who underwent awake craniotomy under conscious sedation
      using Fentanyl and Propofol infusion until December 2005. The drugs were titrated
      (Bispectral monitoring was used in 16 patients) to facilitate intermittent
      intraoperative neurological testing. All patients received scalp blocks with a
      mixture of bupivacaine and lignocaine with adrenaline. Haloperidol and
      ondansetron were administered in all patients at induction of anesthesia.
      RESULTS: All patients completed the procedure. One patient each needed
      endotracheal intubation and LMA for airway control during closure, while another
      required CPAP perioperatively because of desaturation to <80%. There was
      significantly decreased use of anesthetics (P<0.001) and a trend towards
      reduction in complications (e.g. respiratory depression and deep sedation)
      (P>0.05) with the use of BIS as compared to without BIS. Intraoperative
      complications were hypertension (19%), tight brain (14.2%), focal seizure (9.5%)
      respiratory depression (7.1%), deep sedation (7.1%), tachycardia (7.1%) and
      bradycardia. Two patients desaturated to <95%. 23.8% patients developed transient
      neurological deficits. The most frequent postoperative complications were PONV
      (19%) and seizures (16.6%). CONCLUSIONS: With the use of advanced monitoring and
      newer anesthetics, awake craniotomy is a relatively safe procedure with an
      accepted rate of complications.

PMID- 18040112
TI  - Syndrome of spontaneous cerebrospinal fluid hypovolemia: report of six cases.
AB  - Syndrome of spontaneous cerebrospinal fluid hypovolemia (SCH) is a rare cause of
      new onset headache. We report six cases of SCH presenting with new onset
      headache. All six cases were females. Acute onset orthostatic headache and neck
      pain were the chief characteristics of SCH in our cases. The MRI brain showed
      pachymeningeal gadolinium enhancement in all patients. Spinal extradural CSF
      collection was demonstrable on MRI in three cases. All cases improved with
      conservative therapy. High index of clinical suspicion and contrast enhanced MRI
      brain is the key to accurate diagnosis in the majority of cases.

PMID- 18040113
TI  - Magnetic resonance spectroscopy study in basal ganglia of patients with myoclonic
      epilepsy with ragged-red fibers.
AB  - Abnormal magnetic resonance spectroscopic (MRS) signals in the basal ganglia may
      be one of the characteristics in mitochondrial disease. We report MRS study in a
      family with myoclonic epilepsy with ragged-red fibers (MERRF). Their MRS studies
      over the basal ganglia revealed decreased N-acetylaspartate/creatine ratio and
      increased choline/creatine ratio in the four symptomatic members, but normal in
      the two asymptomatic members. However, negative MRI study was found in all
      members of this family. Our report suggests that the increased choline/creatine
      ratio in basal ganglia MRS may be one of the early information to suspect MERRF
      disease.

PMID- 18040114
TI  - Teflon sponge shunt for recurrent arachnoid cyst.
AB  - A 50-year-old female presented with complaints of progressive ataxia.
      Investigations showed a large intradural arachnoid cyst located anterior to the
      brainstem. Following marsupialization of the cyst she improved remarkably in her
      symptoms. The symptoms recurred nine months later and investigations revealed
      recurrence of the cyst. The cyst was evacuated again and two Teflon sponge sheets
      were placed such that they traversed the length of the cyst cavity and extended
      into the cisterna magna. At follow-up after 25 months, there has been no
      recurrence of symptoms or the cyst. The role and advantages of Teflon sponge in
      such cases is evaluated.

PMID- 18040115
TI  - Worsening of cavernous sinus dural arteriovenous fistula with incomplete superior
      ophthalmic thrombosis after palliative transarterial embolization.
AB  - Worsening of ocular symptoms in cavernous sinus dural arteriovenous fistulae
      (CSDAVF) is rarely due to superior ophthalmic vein (SOV) thrombosis after
      palliative transarterial embolization and may resolve spontaneously. We present a
      unique case of a 38-year-old female whose ocular symptoms worsened three days
      after palliative embolization. Repeat angiography revealed incomplete thrombus of
      SOV and severe orbital venous congestion. Complete occlusion of the CSDAVF was
      achieved by urgent transvenous embolization through the SOV and the patient's
      ocular symptoms and visual impairment recovered. In such situations repeat
      angiogram may be needed in evaluating the subtle angiographic changes and
      curative embolization may be necessary.

PMID- 18040116
TI  - Postural tremor induced by paint sniffing.
AB  - Volatile substance abuse is the intentional inhalation of volatile solvents,
      aerosols, gases or nitrates for the purpose of intoxication. This practice is
      more common among young people, due, in part, to the low cost and ready
      availability of these inhalants. In this report, we present the case of a 22-year
      old male with a seven-year history of chronic paint sniffing. The patient
      presented with vigorous postural and kinetic tremor in both hands. A neurological
      examination revealed a bilateral, non-fatiguing geotropic positional nystagmus
      and a mild ataxia together with dysdiadochokinesis. He also had a mild chronic
      encephalopathy. Following treatment with clonazepam, the tremors subsided, but
      were not completely controlled.

PMID- 18040117
TI  - Treatment of traumatic trigeminal-cavernous fistula by coil embolization and
      compression of carotid artery.
AB  - We report a case of a traumatic cavernous fistula supplied by a persistent
      primitive trigeminal artery. The process of treatment was unique in this case.
      Fistula was subcompletely occluded by coiling from primitive trigeminal artery.
      Residual fistula was helped to form thrombosis by compression of the carotid
      artery with hand in the procedure. Long-term follow-up was satisfactory.
      Traumatic cavernous fistula supplied by a persistent primitive trigeminal artery
      could be treated by embolization and temporal compression of the parent artery
      might be useful for residual minimal fistula.

PMID- 18040118
TI  - Dysmyelinating neuropathy in benign form of megalencephalic leukoencephalopathy
      with subcortical cysts: a novel observation from south India.
AB  - A 37-year-old gentleman presented with macrocephaly since early childhood and
      progressive impairment of motor and cognitive functions. Magnetic resonance
      imaging revealed extensive white matter involvement and frontotemporal
      subcortical cysts. Absent ankle jerk and abnormal nerve conduction study raised a
      possibility of associated peripheral neuropathy. Sural nerve biopsy was
      suggestive of dysmyelinating neuropathy. This report serves to expand the
      clinical spectrum of this rare leukodystrophy.

PMID- 18040119
TI  - Postoperative reversible deterioration in a spinal dural arteriovenous fistula.
AB  - This 61-year-old man presented with weakness and sensory disturbance in the legs.
      There was a spinal dural arteriovenous fistula (SDAVF) fed by the left sixth
      intercostal artery with dorsal perimedullary drainage. Surgical division of the
      perimedullary drainage led to rapid neurological improvement. However, on the
      second postoperative day he experienced transient deterioration of second neuron
      function in the left upper lumbar segment resulting in motor weakness of the
      proximal leg muscles, absence of the patellar deep tendon reflex and thigh pain.
      No radiological findings explaining this deterioration were obtained. He was
      treated conservatively and all segmental symptoms and signs subsided by the fifth
      postoperative day. Although the precise mechanisms underlying the dramatic but
      often reversible deterioration after radical SDAVF treatment remain to be
      determined, we postulate that this was attributable to postoperative segmental
      venous hemodynamic changes based on the neurological changes.

PMID- 18040120
TI  - An incidentally detected third ventricle chordoid glioma.
AB  - Chordoid glioma is a rare low-grade tumor located in the third ventricle
      hypothalamic region. Since its first report, 37 cases have been described in the
      literature. We report on an additional case that we considered significant
      because of its incidental detection and its uneventful surgical removal.

PMID- 18040122
TI  - Association between pituitary adenomas and intracranial aneurysms: an
      illustrative case and review of the literature.
AB  - The co-existence of cerebral aneurysms and pituitary adenomas is rare. Here, we
      report a patient with a coexisting anterior communicating artery aneurysm and a
      pituitary adenoma and review the available literature concerning this phenomenon.
      There is a debate in the literature regarding any causal relationship between
      aneurysms and pituitary tumors, although there are many reports of aneurysms
      caused by trauma or radiation following treatment of pituitary tumors. These
      simultaneous lesions are best diagnosed with magnetic resonance imaging with
      magnetic resonance angiography. Craniotomy for simultaneous aneurysm clipping and
      resection of the pituitary tumor is the best treatment option.

PMID- 18040121
TI  - Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India.
AB  - The authors report an Indian adult female patient with a history of generalized
      tonic clonic seizures who developed severe features of phenytoin (DPH) toxicity
      on therapeutic dosage of this antiepileptic drug. Administration of 300 mg/day of
      DPH in this patient resulted in toxic symptoms associated with an excessive serum
      DPH concentration of 33 microg/ml. The PCR-RFLP analysis revealed a homozygosity
      involving CYP2C9*3*3. This mutation results in a marked decrease in the enzymatic
      activity (CYP2C9) and leads to a decreased clearance of the drug which can lead
      to severe acute and chronic toxicity. On switching the antiepileptic therapy from
      DPH to sodium valproate, there was reversal of both.

PMID- 18040123
TI  - Acute intermittent porphyria presenting with neurological emergency: review of
      six cases.
AB  - Acute intermittent porphyria presenting with short duration of gastrointestinal
      symptoms followed by rapidly progressive fulminant neurological syndrome during
      first attack is relatively uncommon. It is a neurological emergency and mimics
      many other psychiatric and medical disorders and can be fatal if it remains
      undiagnosed and untreated. Further, specific treatment in the form of Heme
      arginate is not universally available and very costly, so high clinical suspicion
      and early diagnosis and management of acute attack and prevention of further
      attacks are very important. We report a series of six cases who presented with
      convulsion and/or polyneuropathy early in the course of disease to highlight this
      fact.

PMID- 18040124
TI  - Intracerebral hemorrhage in a patient with Churg-Strauss syndrome.

PMID- 18040125
TI  - Survival in rhinocerebral mucormycosis: is iron the key?

PMID- 18040126
TI  - Bilateral thalamic involvement in dengue infection.

PMID- 18040127
TI  - Nuchal extra-abdominal aggressive fibromatosis of desmoid type in a 77-year-old
      female.

PMID- 18040128
TI  - Paradoxical progression of conus tuberculoma during chemotherapy of tuberculous
      meningitis.

PMID- 18040129
TI  - Variability of the palmar cutaneous branch median nerve sensory nerve action
      potential with carpal tunnel syndrome.

PMID- 18040130
TI  - Subperiosteal hematoma of the orbit associated with subfrontal hematoma
      presenting as proptosis.

PMID- 18040131
TI  - Ganglion: an uncommon cause of compressive peroneal neuropathy.

PMID- 18040132
TI  - Relapsing myelopathy as the initial manifestation of primary central nervous
      system angiitis.

PMID- 18040133
TI  - Spinal cord involvement and ganglionitis in leprosy.

PMID- 18040134
TI  - Osteochondroma of rib with neural foraminal extension and cord compression.

PMID- 18040135
TI  - Giant sphenoethmoidal nasopaharyngeal schwannoma with anterior skull base
      extension managed by a total anterior transbasal approach.

PMID- 18040136
TI  - Lumbosacral subdural hematoma following a ruptured aneurysmal subarachnoid
      hemorrhage.

PMID- 18040137
TI  - Complex spontaneous extracranial-intracranial collateralization in progressive
      systemic atherosclerotic disease.

PMID- 18040138
TI  - Scalp and intracranial metastasis from pleomorphic adenocarcinoma of the parotid
      gland.

PMID- 18040139
TI  - Elevated cerebrospinal fluid levels of placental alkaline phosphatase and beta
      human chorionic gonadotrophin in a case of intracranial germinoma with normal
      levels in blood.

PMID- 18040140
TI  - An extra hill in a poly-hill sign in a patient with facioscapulohumeral
      dystrophy.

PMID- 18040141
TI  - Subdural hematoma, subarachnoid hemorrhage and intracerebral parenchymal
      hemorrhage secondary to cerebral sinovenous thrombosis: a rare combination.

PMID- 18040143
TI  - MALT lymphoma : recent advances in aetiology and molecular genetics.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is a common low grade B-cell
      lymphoma arising from a background of chronic inflammatory disease at a number of
      mucosal sites. Those originating in the stomach are causatively linked to
      Helicobacter pylori infection and eradication of the bacterium with antibiotics
      leads to long-term complete regression of the lymphoma in aproximately 70% of
      cases. Now, there is further evidence of linking Campylobacter jejuni, Borrelia
      burgdorferi and Chlamydia psittaci infection with immunoproliferative small
      intestine disease, MALT lymphoma of the skin and ocular adnexa respectively.
      t(11;18)/API2-MALT1, t(1;14)/IGH-BCL10, t(14;18)/IGH-MALT1 and t(3;14)/IGH-FOXP1
      occur at considerably variable incidences in MALT lymphomas of different sites.
      The first three chromosome translocations are specifically associated with the
      MALT lymphoma entity and the oncogenic products of these translocations have been
      shown to target a common molecular pathway, i.e. the nuclear factor-kappaB
      pathway. Here, I review the recent advances in our understanding of the
      association of microbial pathogens with MALT lymphoma of various sites and the
      molecular genetics underlying the lymphoma development.

PMID- 18040144
TI  - Radioimmunotherapy for non-hodgkin lymphoma : historical perspective and current
      status.
AB  - Radioimmunotherapy (RIT) treatment for lymphoma is a novel targeted therapeutic
      approach. Several years of development of radioimmunotherapeutic compounds came
      to fruition in February of 2002 when (90)Y-ibritumomab tiuxetan (Zevalin, Y2B8)
      was approved in the USA and later in Europe, for the treatment of relapsed or
      refractory, low grade or transformed B-cell lymphoma. (90)Y-ibritumomab tiuxetan
      utilizes a monoclonal anti-CD20 antibody to deliver beta-emitting yttium-90 to
      the malignant B-cells. Clinical trials have demonstrated its efficacy, which is
      largely independent of the intrinsic activity of the anti-CD20 antibody. A
      similar anti-CD20 radiotherapeutic compound, (131)I-tositumomab, was subsequently
      approved in the USA. The advantages of increased efficacy compared to the naked
      antibody are gained at the expense of myelotoxicity which is dose limiting but
      reversible. Studies exploring expanded applications of radioimmunotherapy have
      been recently completed or are under way. It is hoped that RIT will be an ideal
      agent for consolidation after chemotherapy for both indolent and aggressive non
      Hodgkin lymphoma as well as a useful addition to preparatory high dose regimens
      prior to transplant. RIT has been shown to be an effective and clinically
      relevant complementary therapeutic approach for patients with lymphoma.

PMID- 18040145
TI  - Enhancement of anti-tumor cytotoxicity of expanded gammadelta T Cells by
      stimulation with monocyte-derived dendritic cells.
AB  - In order to establish the method of generating powerful gammadelta T cells for
      anti-tumor immunotherapy, we investigated the effects of monocyte-derived
      dendritic cells (mo-DCs) on anti-tumor cytotoxicity of expanded gammadelta T
      cells. Activation of gammadelta T cells co-cultured for 2-3 days with immature or
      mature mo-DCs was evaluated by CD69 expression and anti-tumor cytotoxicity using
      two assays : the 5- (and 6-) carboxyfluorescein diacetate, succinimidyl ester
      based cytotoxicity assay and the calcein-AM-based Terascan assay. gammadelta T
      cells were used as effector cells and myeloma cell line (RPMI8226) or chronic
      myelogenous leukemia blastic crisis cell line (C2F8) were used as target cells.
      CD69 expression on gammadelta T cells was enhanced by co-culture with both
      immature and mature mo-DCs in a cell-number-dependent fashion. CD69 expression
      was enhanced after addition of mo-DCs of either autologous or allogeneic origin.
      Activation of gammadelta T cells with mo-DCs enhanced anti-tumor cytotoxicity of
      gammadelta T cells against RPMI8226 and C2F8 in an effector-to-target ratio
      dependent manner. Activation of gammadelta T cells by mo-DCs was associated with
      the enhancement of anti-tumor cytotoxicity of gammadelta T cells. Potent
      gammadelta T cells activated by mo-DCs were considered to be applicable to an
      efficient gammadelta T cell-mediated immunotherapy for tumors.

PMID- 18040146
TI  - Primary hepatic follicular lymphoma : a case report and discussion of
      chemotherapy and favorable outcomes.
AB  - This report concerns a rare case of follicular lymphoma with features suggestive
      of primary hepatic lymphoma. At the disease onset, multiple nodular lesions in
      the liver and small para-aortic nodes were detected by abdominal magnetic
      resonance imaging without generalized lymphadenopathy. After careful observation
      for three months, lymphadenopathy was observed in the right occipital, para
      aortic, and bilateral inguinal regions. The patient was treated with R-CHOP
      (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and
      achieved complete remission for more than 2 years. To the best of our knowledge,
      this is the ninth report of primary hepatic follicular lymphoma. Insufficient
      cases have been reported to determine the long-term outcome and clinical
      characteristics of primary hepatic follicular lymphoma. However, it seems that
      patients with primary hepatic follicular lymphoma that are treated with
      appropriate chemotherapy with or without surgical resection have favorable
      outcomes.

PMID- 18040147
TI  - Spontaneous regression of bilateral conjunctival extranodal marginal zone B-cell
      lymphoma of mucosa-associated lymphoid tissue.
AB  - We report the case of a patient who showed spontaneous regression of bilateral
      conjunctival extranodal marginal zone B-cell lymphoma of mucosa-associated
      lymphoid tissue (MALT lymphoma). A 72-year-old man underwent excisional biopsy
      for salmon-pink lesions involving the whole circumference of the conjunctiva in
      the right eye and the lower fornix in the left eye. Histopathology and
      immunohistochemistry showed MALT lymphoma with immunoglobulin kappa monotype
      shared by the lesions in both eyes. Because the patient had recurrent pulmonary
      tuberculosis, radiation initially planned for the large residual lesion in the
      right eye was postponed. Over two years, including 6 mon with anti-tuberculous
      treatment, the large lesion in the right eye showed spontaneous regression. The
      spontaneous regression of conjunctival MALT lymphoma observed in this patient
      suggests that following excisional biopsy for histopathological diagnosis,
      observation is a treatment option.

PMID- 18040148
TI  - Splenic inflammatory pseudotumor (inflammatory myofibroblastic tumor).
AB  - We report a case of a splenic inflammatory pseudotumor (myofibroblastic tumor) in
      a 43-year-old man with a 5-year history of chronic bronchitis and sleep apnea
      syndrome. The patient was hospitalized because of a screen-detected splenic mass
      lesion. His sputum cultures revealed Mycobacterium avium complexes on only one
      occasion. Imaging studies revealed a 7 cm solitary tumorous lesion, and
      differential diagnoses of splenic hamartoma, hemangioma, lymphoma, and
      angiosarcoma were obtained from the radiologist. A splenectomy followed by
      pathological investigations was performed. By histology, the lesion contained
      fibroblastic or myofibroblastic spindle cell proliferations, accompanied by
      variable degrees of inflammatory cell infiltration. Ziehl-Neelsen staining did
      not reveal acid-fast bacteria. Immunohistochemically, the fibroblastic or
      myofibroblastic spindle cells were positive for vimentin, human smooth muscle
      actin, and muscle actin, but negative for desmin, CD8, CD21, CD23, CD35, p80,
      Epstein-Barr virus LMP, and human herpesvirus type 8. The infiltrating lymphoid
      cells demonstrated a nonneoplastic pattern. The results of in situ hybridization
      for Epstein-Barr virus encoded RNA were negative. The postoperative course was
      uneventful and he has had no recurrence in 22 months. His sleep apnea syndrome
      and chronic bronchitis have resolved spontaneously since the splenectomy.

PMID- 18040149
TI  - [Paramyxovirus budding].
AB  - Our knowledge about envelope virus budding has been dramatically increased, since
      L-domain motifs were identified within their matrix and retroviral Gag proteins
      which drive virus budding. These viral proteins have been shown to interact with
      host cellular proteins involved in endocytosis and/or multi-vesicular body (MVB)
      sorting via their L-domains. Since budding of many enveloped viruses have been
      reported to be dependent on the activity of cellular Vps4, which catalyzes the
      disassembly of ESCRT machinery in the final step of protein sorting, this
      cellular function is believed to be utilized for efficient virus budding.
      However, for many enveloped viruses, L-domain motifs have not yet been
      identified, and the involvement of MVB sorting machinery in virus budding is
      still unknown. In this review, we will focus on paramyxoviruses among such
      viruses, and discuss their budding with the latest information.

PMID- 18040150
TI  - [Subcellular locations at which HIV-1 assembles].
AB  - Virus particle formation of HIV-1 is driven by the viral structural protein Gag.
      In most cell types including T cells, Gag assembles into virus particles at the
      plasma membrane whereas, in HIV-1-infected macrophages, Gag and virus particles
      have been shown to accumulate in intracellular vesicles. At the moment, what
      causes this difference between cell types remains unknown. However, recent
      findings on the relationships between Gag and the cellular membrane system have
      substantially increased our understanding of the mechanisms by which sites of
      virus assembly are determined. I will review our current knowledge regarding the
      roles played by endosomal trafficking pathways, membrane microdomains, and plasma
      membrane lipids, and discuss the physiological significance of the interactions
      between Gag and specific membrane structures.

PMID- 18040151
TI  - [Anticancer immunotherapy using inactivated Sendai virus particles].
AB  - Ultraviolet-inactivated, replication-defective Sendai virus particles
      (Hemagglutinating virus of Japan envelope, HVJ-E) injected into murine colon
      carcinoma (CT26) tumors growing in syngeneic Balb/c mice eradicated 60-80% of the
      tumors and obviously inhibited the growth of the remainder. Induced adaptive anti
      tumor immune responses were dominant in the tumor eradication process because the
      effect was abrogated in severe combined immunodeficient (SCID) mice. Murine and
      human dendritic cells (DCs) underwent dose-dependent maturation by HVJ-E in
      vitro. Profiles of cytokines secreted by DCs after HVJ-E stimulation showed that
      the amount of IL-6 released was comparable to that elicited by live HVJ. Real
      time RT-PCR and immunohistochemistry revealed that HVJ-E induced a remarkable
      infiltration of DCs, CD4+ and CD8+ T cells into tumors and CT26 specific
      cytotoxic T lymphocytes (CTL) were induced. On the other hand, conditioned medium
      from DCs stimulated by HVJ-E (H-DCCM) rescued CD4+CD25- effector T cell
      proliferation from Foxp3+CD4+CD25+ regulatory T cell (Treg) mediated suppression
      and IL-6 was presumably dominant for this phenomenon. We also confirmed such
      rescue in mice treated with HVJ-E in vivo. Moreover, anti-tumor effect of HVJ-E
      was significantly reduced by an in vivo blockade of IL-6 signaling. Depending on
      cancer cell types, it is also expected that HVJ-E eradicates tumor by its direct
      cytotoxity against cancer cells or activating NK cells. Because it can enhance
      anti-tumor immunity and simultaneously remove Treg mediated suppression, HVJ-E
      shows promise as a novel therapeutic for cancer immunotherapy.

PMID- 18040152
TI  - [Sendai virus vector: vector development and its application to health care and
      biotechnology].
AB  - Sendai virus (SeV) is an enveloped virus with a nonsegmented negative-strand RNA
      genome and a member of the paramyxovirus family. We have developed SeV vector
      which has shown a high efficiently of gene transfer and expression of foreign
      genes to a wide range of dividing and non-dividing mammalian cells and tissues.
      One of the characteristics of the vector is that the genome is located
      exclusively in the cytoplasm of infected cells and does not go through a DNA
      phase; thus there is no concern about unwanted integration of foreign sequences
      into chromosomal DNA. Therefore, this new class of "cytoplasmic RNA vector", an
      RNA vector with cytoplasmic expression, is expected to be a safer and more
      efficient viral vector than existing vectors for application to human therapy in
      various fields including gene therapy and vaccination. In this review, I describe
      development of Sendai virus vector, its application in the field of biotechnology
      and clinical application aiming to treat for a large number of diseases including
      cancer, cardiovascular disease, infectious diseases and neurologic disorders.

PMID- 18040153
TI  - [Gene engineering of the adenovirus vector].
AB  - The adenovirus vector is very attractive tool not only for the gene therapy but
      also for the basic sciences. However, because a construction method of this
      vector had been complex, only limited scientists had constructed and enjoyed the
      benefits. Recently, various methods were developed and the researchers came to be
      able to choose an efficient method, which is the COS-TPC method, or a concise
      procedure, which is the intact-genome transfection method (in vitro ligation
      method). Here we described not only these methods but also new method to
      construct the various Ads simultaneously using the recombinase-mediated cassette
      exchange (RMCE) by the site-specific recombinase. And also we want to refer the
      possibility to the worth of the vector, especially the vector of the expression
      switch.

PMID- 18040154
TI  - [Gene therapy using AAV].
AB  - AAV (adeno-associated virus) vectors are considered to be promising gene-delivery
      vehicles for gene therapy, because they are derived from non-pathogenic virus,
      efficiently transduce non-dividing cells, and cause long-term gene expression.
      Appropriate AAV serotypes are utilized depending on the type of target cells.
      Among various neurological disorders, Parkinson's disease (PD) is one of the most
      promising candidates of gene therapy. PD is a progressive neurodegenerative
      disorder that predominantly affects dopaminergic neurons in the substantia nigra.
      One of the major approaches to gene therapy of PD is the intrastriatal expression
      of dopamine (DA)-synthesizing enzyme genes. As for the initial step of clinical
      application, AAV vector-mediated AADC (aromatic L-amino acid decarboxylase; the
      enzyme converting L-DOPA to DA) gene transfer in combination with oral
      administration of L-DOPA would be appropriate, since DA production can be
      regulated by adjusting the dose of L-DOPA. Second, intramuscular injection of AAV
      vectors is appropriate to protein-supplement gene therapy. Monogenic diseases
      such as hemophilia and Fabry disease are suitable candidates. Regarding cancer
      gene therapy, AAV vectors may be utilized to inhibit tumor angiogenesis,
      metastasis, and invasion. When long-term transgene expression in stem cells is
      needed, a therapeutic gene should be introduced with a minimal risk of
      insertional mutagenesis. To this end, site-specific integration into the AAVS1
      locus on the chromosome 19 (19q13.4) by using the integration machinery of AAV
      would be particularly valuable.

PMID- 18040155
TI  - [Oncolytic virotherapy using replication-competent herpes simplex viruses].
AB  - Oncolytic virotherapy using replication-competent viruses has attracted us as a
      new modality for cancer treatment. The fundamental concept of oncolytic
      virotherapy is that the viruses selectively replicate in and lyse tumor cells.
      Since 1997, numbers of clinical trials have been done in over 500 cancer
      patients. However, the results of those trials have been disappointing in most
      cases. We have isolated a spontaneously occurring herpes simplex virus type 1
      mutant, designated HF10, which efficiently replicates and induces cell fusion in
      most transformed cells, but is highly attenuated in mice. HF10 has a number of
      deletions and insertions in the genome, resulting in the lack of the functional
      expression of UL43, UL49.5, UL55, UL56 and latency-associated transcripts. We
      have found that HF10 can be used as an oncolytic virus for treatment of malignant
      tumors in various animal models. Clinical trials have shown that intratumoral
      injection of HF10 can induce extensive tumor cell death in patients with
      recurrent breast cancer and head and neck squamous cell carcinoma without
      significant adverse effects. HF10 is a promising agent for use in oncolytic
      virotherapy in non-central nervous system malignancies.

PMID- 18040156
TI  - [Analysis of Aichi virus replication].
AB  - Aichi virus is a member of the Family Picornaviridae. This virus was first
      isolated in 1989 from a stool specimen from a patient with oyster-associated
      gastroenteritis in Aichi, Japan. We analyzed the function of the 5' terminal
      region of the genome and the leader protein in virus replication. The results
      indicate that both the 5' terminal region of the genome and the leader protein
      are involved in viral RNA replication and encapsidation.

PMID- 18040157
TI  - [Feline immunodeficiency virus tropism].
AB  - Feline immunodeficiency virus (FIV) induces a disease similar to acquired
      immunodeficiency syndrome (AIDS) in cats, yet in contrast to human
      immunodeficiency virus (HIV), CD4 is not the viral receptor. We identified a
      primary receptor for FIV as CD134 (OX40), a T cell activation antigen and
      costimulatory molecule. CD134 expression promotes viral binding and renders cells
      permissive for viral entry, productive infection, and syncytium formation.
      Infection is CXCR4-dependent, analogous to infection with X4 strains of HIV.
      Thus, despite the evolutionary divergence of the feline and human lentiviruses,
      both viruses use receptors that target the virus to a subset of cells that are
      pivotal to the acquired immune response. Further, we applied the new method for
      FIV receptor to Ebola virus entry factors with some modifications, and identified
      receptor-type tyrosine kinases, Axl and Dtk (members of Tyro3 family).
      Distribution of the molecules matches well with the Ebola virus tropism.

PMID- 18040158
TI  - [Reverse genetics system for measles virus: establishment and applications for
      analysis of virus replication and pathogenesis].
AB  - In 1990 Kobune et al. succeeded in isolating pathogenic wild-type strains of
      measles virus (MV) using a marmoset B-lymphoblastoid cell line B95a. Their data
      indicated that MV strains that have been used in laboratories are attenuated
      strains through the adaptation to grow in a variety of cultured cells. We have
      established a very efficient reverse genetics system that allows us to engineer
      the genome of a wild-type MV strain at will by site-directed mutagenesis or
      recombination. Using the system it was shown that (1) the H protein determines
      tropism of MV, (2) the M protein regulates mode of MV spread, (3) the C protein
      inhibits host innate immune responses, and (4) the long untranslated regions in
      the M and F genes function to moderate cytopathogenicity by MV. These data
      advanced our understanding of molecular bases for MV pathogenicity and mechanisms
      of MV adaptation to grow in cultured cells.

PMID- 18040159
TI  - [Important points in virus research using recombinant DNA technology].
AB  - Cartagena Protocol on Biosafety to the Convention on Biological Diversity seeks
      to protect biological diversity from potential risks posed by living modified
      organisms (LMOs) resulting from modern biotechnology. This protocol was ratified
      in Japan after establishing domestic law and regulations for the protocol. In the
      domestic law, use of LMOs is classified into type 1 use (use without containment
      measures) and type 2 use (use with containment measures). According to the
      domestic law, most of experiments using recombinant viruses are required for the
      approval of the Minister. In this article, we will explain Cartagena Protocol and
      the Japanese domestic low and indicate an example of application form for the
      approval of the Minister.

PMID- 18040160
TI  - Investigating the empirical evidence for understanding vulnerability and the
      associations between poverty, HIV infection and AIDS impact.

PMID- 18040161
TI  - HIV infection does not disproportionately affect the poorer in sub-Saharan
      Africa.
AB  - BACKGROUND: Wealthier populations do better than poorer ones on most measures of
      health status, including nutrition, morbidity and mortality, and healthcare
      utilization. OBJECTIVES: This study examines the association between household
      wealth status and HIV serostatus to identify what characteristics and behaviours
      are associated with HIV infection, and the role of confounding factors such as
      place of residence and other risk factors. METHODS: Data are from eight national
      surveys in sub-Saharan Africa (Kenya, Ghana, Burkina Faso, Cameroon, Tanzania,
      Lesotho, Malawi, and Uganda) conducted during 2003-2005. Dried blood spot samples
      were collected and tested for HIV, following internationally accepted ethical
      standards and laboratory procedures. The association between household wealth
      (measured by an index based on household ownership of durable assets and other
      amenities) and HIV serostatus is examined using both descriptive and multivariate
      statistical methods. RESULTS: In all eight countries, adults in the wealthiest
      quintiles have a higher prevalence of HIV than those in the poorer quintiles.
      Prevalence increases monotonically with wealth in most cases. Similarly for
      cohabiting couples, the likelihood that one or both partners is HIV infected
      increases with wealth. The positive association between wealth and HIV prevalence
      is only partly explained by an association of wealth with other underlying
      factors, such as place of residence and education, and by differences in sexual
      behaviour, such as multiple sex partners, condom use, and male circumcision.
      CONCLUSION: In sub-Saharan Africa, HIV prevalence does not exhibit the same
      pattern of association with poverty as most other diseases. HIV programmes should
      also focus on the wealthier segments of the population.

PMID- 18040162
TI  - The socioeconomic determinants of HIV incidence: evidence from a longitudinal,
      population-based study in rural South Africa.
AB  - BACKGROUND: Knowledge of the effect of socioeconomic status on HIV infection in
      Africa stems largely from cross-sectional studies. Cross-sectional studies suffer
      from two important limitations: two-way causality between socioeconomic status
      and HIV serostatus and simultaneous effects of socioeconomic status on HIV
      incidence and HIV-positive survival time. Both problems are avoided in
      longitudinal cohort studies. METHODS: We used data from a longitudinal HIV
      surveillance and a linked demographic surveillance in a poor rural community in
      KwaZulu-Natal, South Africa, to investigate the effect of three measures of
      socioeconomic status on HIV incidence: educational attainment, household wealth
      categories (based on a ranking of households on an assets index scale) and per
      capita household expenditure. Our sample comprised of 3325 individuals who tested
      HIV-negative at baseline and either HIV-negative or -positive on a second test
      (on average 1.3 years later). RESULTS: In multivariable survival analysis, one
      additional year of education reduced the hazard of acquiring HIV by 7% (P =
      0.017) net of sex, age, wealth, household expenditure, rural vs. urban/periurban
      residence, migration status and partnership status. Holding other factors equal,
      members of households that fell into the middle 40% of relative wealth had a 72%
      higher hazard of HIV acquisition than members of the 40% poorest households (P =
      0.012). Per capita household expenditure did not significantly affect HIV
      incidence (P = 0.669). CONCLUSION: Although poverty reduction is important for
      obvious reasons, it may not be as effective as anticipated in reducing the spread
      of HIV in rural South Africa. In contrast, our results suggest that increasing
      educational attainment in the general population may lower HIV incidence.

PMID- 18040163
TI  - Explaining continued high HIV prevalence in South Africa: socioeconomic factors,
      HIV incidence and sexual behaviour change among a rural cohort, 2001-2004.
AB  - OBJECTIVES: To estimate HIV incidence and explore evidence for changing sexual
      behaviour over time among men and women belonging to different socioeconomic
      groups in rural South Africa. DESIGN AND METHODS: A cohort study conducted
      between 2001 and 2004; 3881 individuals aged 14-35 years enumerated in eight
      villages were eligible. At least three household visits were made to contact each
      eligible respondent at both timepoints. Sexual behaviour data were collected in
      structured, respondent-focused interviews. HIV serostatus was assessed using an
      oral fluid enzyme-linked immunosorbent assay at each timepoint. RESULTS: Data on
      sexual behaviour were available from 1967 individuals at both timepoints. A total
      of 1286 HIV-negative individuals at baseline contributed to the analysis of
      incidence. HIV incidence was 2.2/100 person-years among men and 4.9/100 person
      years in women, among whom it was highest in the least educated group. Median age
      at first sex was lower among later birth cohorts. A higher number of previously
      sexually active individuals reported having multiple partners in the past year in
      2004 than 2001. Condom use with non-spousal partners increased from 2001 to 2004.
      Migrant men more often reported multiple partners. Migrant and more educated
      individuals of both sexes and women from wealthier households reported higher
      levels of condom use. DISCUSSION: HIV incidence is high in rural South Africa,
      particularly among women of low education. Some risky sexual behaviours (early
      sexual debut, having multiple sexual partners) are becoming more common over
      time. Condom use is increasing. Existing HIV prevention strategies have only been
      partly effective in generating population-level behavioural change.

PMID- 18040164
TI  - Household and community income, economic shocks and risky sexual behavior of
      young adults: evidence from the Cape Area Panel Study 2002 and 2005.
AB  - OBJECTIVE: To describe recent trends in adolescent sexual behavior in Cape Town,
      South Africa, and to determine whether household and community poverty and
      negative economic shocks predict risky sexual behavior. DATA: Matched survey data
      on 2993 African and coloured youth from the Cape Area Panel Study 2002 and 2005.
      MAIN OUTCOME MEASURES: Sexual debut, multiple sexual partners in past year,
      condom use at last sex, measured in 2002 and 2005. METHODS: We tested for changes
      over time in reported sexual behavior and estimate multivariate probit models to
      measure the association between 2002 individual, household and community
      characteristics and 2005 sexual behavior. RESULTS: There was a statistically
      significant increase in condom use and a decrease in the incidence of multiple
      sexual partners between 2002 and 2005 for young women aged 17-22 years. Young
      women in households with 10% higher income were 0.53% less likely to debut
      sexually by 2005; young men in communities with a 10% higher poverty rate were 5%
      less likely to report condom use at last sex. Negative economic shocks are
      associated with a 0.04% increase in the probability of multiple partnerships for
      young women. Education is positively correlated with sexual debut for young women
      and with multiple partnerships for both sexes. CONCLUSION: Trends in sexual
      behavior between 2002 and 2005 indicate significant shifts towards safer
      practices. There is little evidence of a relationship between negative economic
      shocks, household and community poverty, and risky behavior. We hypothesize that
      the unexpected positive relationship between education and sexual debut may be
      driven by peer effects in schools with substantial age mixing.

PMID- 18040165
TI  - Is poverty or wealth driving HIV transmission?
AB  - Evidence of associations between socioeconomic status and the spread of HIV in
      different settings and at various stages of the epidemic is still rudimentary.
      Few existing studies are able to track incidence and to control effectively for
      potentially confounding factors. This paper reviews the findings of recent
      studies, including several included in this volume, in an attempt to uncover the
      degree to which, and the pathways through which, wealth or poverty is driving
      transmission in sub-Saharan Africa. We investigate the question of whether the
      epidemic is transitioning from an early phase in which wealth was a primary
      driver, to one in which poverty is increasingly implicated. The paper concludes
      by demonstrating the complexity and context-specificity of associations and the
      critical influence of certain contextual factors such as location, gender and age
      asymmetries, the mobility of individuals, and the social ecology of HIV
      transmission. Whereas it is true that poor individuals and households are likely
      to be hit harder by the downstream impacts of AIDS, their chances of being
      exposed to HIV in the first place are not necessarily greater than wealthier
      individuals or households. What is clear is that approaches to HIV prevention
      need to cut across all socioeconomic strata of society and they need to be
      tailored to the specific drivers of transmission within different groups, with
      particular attention to the vulnerabilities faced by youth and women, and to the
      dynamic and contextual nature of the relationship between socioeconomic status
      and HIV.

PMID- 18040166
TI  - HIV incidence and poverty in Manicaland, Zimbabwe: is HIV becoming a disease of
      the poor?
AB  - BACKGROUND: In Zimbabwe, socioeconomic development has a complicated and
      changeable relationship with HIV infection. Longitudinal data are needed to
      disentangle the cyclical effects of poverty and HIV as well as to separate
      historical patterns from contemporary trends of infection. METHODS: We analysed a
      large population-based cohort in eastern Zimbabwe. The wealth index was measured
      at baseline on the basis of household asset ownership. The associations of the
      wealth index with HIV incidence and mortality, sexual risk behaviour, and sexual
      mixing patterns were analysed. RESULTS: The largest decreases in HIV prevalence
      were in the top third of the wealth index distribution (tercile) in both men at
      25% and women at 21%. In men, HIV incidence was significantly lower in the top
      wealth index tercile (15.4 per 1000 person-years) compared with the lowest
      tercile (27.4 per 1000 person-years), especially among young men. Mortality rates
      were significantly lower in both men and women of higher wealth index. Men of
      higher wealth index reported more sexual partners, but were also more likely to
      use condoms. Better-off women reported fewer partners and were less likely to
      engage in transactional sex. Partnership data suggests increasing like-with-like
      mixing in higher wealth groups resulting in the reduced probability of
      serodiscordant couples. CONCLUSION: HIV incidence and mortality, and perhaps
      sexual risk, are lower in higher socioeconomic groups. Reduced vulnerability to
      infection, led by the relatively well off, is a positive trend, but in the
      absence of analogous developments in vulnerable groups, HIV threatens to become a
      disease of the poor.

PMID- 18040167
TI  - The economic impacts of premature adult mortality: panel data evidence from
      KwaZulu-Natal, South Africa.
AB  - Measuring the household level economic impacts of AIDS-related deaths is of
      particular salience in South Africa, a country struggling with a legacy of
      poverty and economic inequality in the midst of an HIV epidemic. Household panel
      data that span more than a decade permit us to resolve many of the statistical
      problems that make it difficult to determine these impacts. After allowing for
      the impact of demographic adjustments and other coping strategies, we found
      evidence that these impacts are quite different across different types of
      households, and that the largest and most persistent effects were in the middle
      ranges of the South African income distribution, that is, households just above
      the poverty line. Households below that level seem less severely affected,
      whereas those above it seem to recover more quickly. All these results need to be
      treated with caution because their statistical precision is weak.

PMID- 18040168
TI  - The financial impact of HIV/AIDS on poor households in South Africa.
AB  - BACKGROUND: Rising mortality rates caused by HIV/AIDS in South Africa have
      substantial and lingering impacts on poor households. METHODS: This is a
      descriptive paper using a new dataset of daily income, expenditure and financial
      transactions collected over a year from a total of 181 poor households in South
      African rural and urban areas. One of the key pathways through which HIV/AIDS
      impacts on household wellbeing is through the socioeconomic impacts of death,
      which this dataset is especially useful in quantifying. RESULTS: The key impacts
      of death on households are funerals and the loss of income. Funerals often cost
      up to 7 months of income. Nearly all households in the sample attempt to cover
      such costs by holding a portfolio of funeral insurance. Despite these efforts to
      insure against funeral costs, 61% of households are underinsured against the cost
      of a funeral. Nearly half the sample households are dependent on a regular wage
      earner, and another quarter are dependent on a grant recipient. Eighty per cent
      of these households would lose over half of their monthly income should the
      highest income recipient in the household die. Even by selling liquid assets,
      only one third of the sample households would be able to maintain their pre-death
      living standards for a year or more. CONCLUSION: Death poses substantial and
      lingering burdens from the funerals that surviving household members need to
      finance and the ongoing loss of income once brought into the household by the
      deceased. These costs pose so great a threat to households that they dominate
      household saving and insurance behavior.

PMID- 18040169
TI  - Father figures: the progress at school of orphans in South Africa.
AB  - OBJECTIVE: To examine the progress in their schooling of maternal and paternal
      orphans in a province of South Africa with high AIDS mortality and contrast it
      with that of both children who lived in different households from their parents
      and children who resided with their parents. METHODS: The KwaZulu-Natal Income
      Dynamics Study is a panel of households first interviewed in 1993. The 1998 and
      2004 waves of fieldwork collected 5477 reports on children aged 8-20 years. We
      studied the determinants of the proportion of these children who had completed 2+
      grades fewer than expected for their year of birth using both household fixed
      effects models and difference-in-difference models fitted to children reported on
      twice. RESULTS: Co-residence with a well-educated mother benefited children's
      schooling, but the fixed-effects models provide no evidence that maternal
      orphanhood or living apart from their mother adversely affected children's
      schooling. In contrast, both paternal orphanhood and belonging to a different
      household from one's father resulted in slower progress at school. Although
      absence of the father was associated with household poverty, this was not why it
      was associated with falling behind at school. DISCUSSION: Both the substantial
      benefits of living with their fathers for children's schooling and the limited
      importance of maternal orphanhood conflict with the results of most studies in
      this issue, including those of other research in the same part of South Africa.
      These findings caution against drawing general conclusions about the impact of
      the AIDS epidemic from a few studies of geographically localized populations.

PMID- 18040170
TI  - Exploring the Cinderella myth: intrahousehold differences in child wellbeing
      between orphans and non-orphans in Amajuba District, South Africa.
AB  - OBJECTIVE: To determine whether differences in wellbeing (defined by a variety of
      education and health outcomes) exist between recent school-aged orphans and non
      orphans who live in the same household in a context of high HIV/AIDS mortality in
      KwaZulu Natal, South Africa. DESIGN: The data come from the first 2 years (2004
      2006) of an ongoing 3-year longitudinal cohort study in a district in KwaZulu
      Natal, the Amajuba Child Health and Well-being Research Project. Using stratified
      cluster sampling based on school and age, we constructed a cohort of 197 recent
      orphans and 528 non-orphans aged 9-16 years and their households and caregivers.
      Household heads, caregivers, and children were interviewed regarding five domains
      of child wellbeing: demographic, economic, educational,
      health/nutrition/lifestyle, and psychosocial status. METHODS: The analytical
      sample consists of 174 children (87 orphans and 87 comparable non-orphans who
      live together) at baseline and 124 children in round 2. We estimated a linear
      regression model using household fixed effects for continuous outcomes (grade
      adjusted for age, annual expenditure on schooling and body mass index) and a
      logit model using household fixed effects for categorical variables
      (malnutrition) to compare co-resident orphans and non-orphans. RESULTS: We found
      no statistically significant differences in most education, health and labour
      outcomes between orphans and the non-orphans with whom they live. Paternal
      orphans are more likely to be behind in school, and recent mobility has a
      positive effect on schooling outcomes.

PMID- 18040171
TI  - Surgical cephalometrics: applications and developments.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Describe the historical origins of modern cephalometry. 2. Identify common
      landmark points on the lateral cephalogram. 3. Describe multiple common clinical
      uses for cephalometry. 4. Exhibit knowledge of developments in imaging and
      analysis alternatives. BACKGROUND: Interest in the dimensions of the human head
      has been present since antiquity. Proportional analysis and measures from
      cadaveric specimens led to the development of radiologic image capture and
      analysis on living subjects. These techniques were originally applied to
      establishing normative values, documenting growth, and diagnosing dentofacial
      disharmonies. This article reviews the origins of cephalometric methodology and
      current developments and applications. METHODS: The authors conducted a MEDLINE
      search and review of all English language articles using the keywords
      "cephalometric" and "cephalometrics." RESULTS: Cephalometrics have undergone
      substantial use and development since the introduction of radiologic imaging on
      living human subjects in 1931. Although frequently associated with orthognathic
      surgery, cephalometrics have been applied to a number of conditions involving
      altered craniofacial morphology. Advances in imaging and computing have led to
      increased interest in three-dimensional and non-x-ray-based assessment of the
      human head. Mathematical models have been applied to standard cephalometric
      information to increase the descriptive accuracy of the complex shapes involved.
      CONCLUSIONS: Cephalometric techniques and analyses are versatile tools that can
      be applied to a wide variety of clinical scenarios involving the craniofacial
      region. New technologies and expanded applications promise to continue the
      development and use of this well-established methodology.

PMID- 18040172
TI  - Raising perforator flaps for breast reconstruction: the intramuscular anatomy of
      the deep inferior epigastric artery.
AB  - BACKGROUND: The deep inferior epigastric artery (DIEA) perforator flap is used
      increasingly for breast reconstruction, preferred as a muscle-sparing operation
      over traditional transverse rectus abdominis musculocutaneous (TRAM) flaps.
      Complications related to the inclusion of rectus abdominis include abdominal wall
      weakness and a predisposition to ventral abdominal wall hernias. DIEA perforator
      flaps still present this complication, with clinical experience demonstrating
      frequent transection of rectus fibers during dissection of perforators. Despite
      this, published descriptions of the DIEA in the literature describe a "direct"
      course through rectus abdominis. This study interprets these clinical findings by
      analyzing the intramuscular course of the perforators. METHODS: The investigation
      was performed on 31 hemiabdominal walls from both fresh and embalmed cadavers,
      using a combination of dissection and radiography of multiple cross-sectional
      planes. Intramuscular distances were measured using the distances between entry
      and exit points of perforators from rectus abdominis muscle, allowing
      characterization of the intramuscular course. RESULTS: Substantial longitudinal
      (mean, 1.52 cm; range, 0.2 to 4.1 cm) and transverse (mean, 1.32 cm; range, 0.3
      to 3.5 cm) distances were traversed by each of the 76 perforators within the
      muscle. CONCLUSIONS: A significant transverse distance was shown to be traversed
      by perforators, confirming the need for division of rectus abdominis fibers
      during operation. This information may help explain the clinical findings of
      abdominal wall morbidity following perforator flaps, and may pave the way for
      improved preoperative selection of patients for DIEA perforator flaps.

PMID- 18040173
TI  - An Intraoperative algorithm for use of the SIEA flap for breast reconstruction.
AB  - BACKGROUND: The deep inferior epigastric perforator (DIEP) flap has been shown to
      be a reliable option for breast reconstruction. A further refinement in the
      transfer of lower abdominal tissue for breast reconstruction is the superficial
      inferior epigastric artery (SIEA) flap. A retrospective study was conducted to
      assess the reliability and examine the outcomes of SIEA flaps for breast
      reconstruction while considering an intraoperative algorithm established in this
      study. METHODS: Ninety-nine SIEA flap reconstructions were performed in 82
      patients in a 3(1/2)-year period. Patients were divided into two groups (before
      and after algorithm implementation), and their medical records were evaluated
      with respect to demographic information, tumor type, tobacco use, ischemic time,
      flap weight, and complications. Potential risk factors for complications were
      also assessed. RESULTS: Of the first 72 SIEA flaps, five were lost because of
      arterial thrombosis. All failed flaps had an SIEA diameter of less than 1.5 mm at
      the level of the lower abdominal incision. In February of 2004 (point T), the
      senior author (A.J.S.) implemented an intraoperative algorithm for flap selection
      that allowed use of the SIEA flap only when the SIEA diameter was 1.5 mm or
      greater than. In the remaining cases, a DIEP flap was used for breast
      reconstruction. After point T, 27 SIEA flap procedures were performed without any
      flap losses. Overall fat necrosis and partial flap loss rates were 1.0 and 5.1
      percent, respectively. No abdominal bulges/hernias were observed. Only smoking at
      the time of surgery was associated with increased donor-site complications (p =
      0.016). CONCLUSION: The intraoperative algorithm helped decrease flap and
      abdominal complication rates for the SIEA flap.

PMID- 18040174
TI  - Dermabond skin closures for bilateral reduction mammaplasties: a review of 255
      consecutive cases.
AB  - BACKGROUND: 2-Octyl cyanoacrylate (Dermabond; Ethicon, Inc., Somerville, N.J.)
      has been available as a skin closure alternative or adjunct since 1997. The
      purpose of this study was to review a large series of 255 consecutive bilateral
      reduction mammaplasty patients to evaluate the safety and efficacy of Dermabond
      for these procedures. METHODS: A review was undertaken of 255 consecutive
      bilateral reduction mammaplasties performed by a single surgeon from 1999 to 2005
      with Dermabond used for skin closure. This series of patients was compared with
      an earlier review by the same surgeon of 415 consecutive bilateral reduction
      mammaplasties using standard layered sutured skin closures. RESULTS: Dermabond
      was associated with decreased operative times compared with the sutured closures
      (93 minutes compared with 118 minutes; 25 minutes or 20 percent less time). The
      rates for minor wound dehiscence (1.18 percent), major wound dehiscence (0.78),
      hypertrophic scar revisions (2.75 percent), and cellulitis (2.75 percent) were
      all lower in the Dermabond group, but these differences were not statistically
      significant. CONCLUSIONS: Dermabond is a safe and effective means of skin closure
      for bilateral reduction mammaplasties. Shortened operative times can lead to
      economic health cost savings. Patient discomfort is minimized and postoperative
      care is simplified.

PMID- 18040175
TI  - The versatility of the superomedial pedicle with various skin reduction patterns.
AB  - BACKGROUND: The inferior pedicle technique remains one of the most commonly used
      techniques in breast reduction surgery, despite lengthy operating times, poor
      nipple sensation, and bottoming-out over time. The superomedial pedicle in
      reduction mammaplasty has previously been described using limited incision
      patterns. This study evaluated the safety and reliability of the superomedial
      pedicle with various skin reduction patterns and compared the surgical time with
      the inferior pedicle technique. METHODS: A total of 279 superomedial breast
      reductions were reviewed over a 6-year period, representing the transition period
      from inferior pedicle to superomedial pedicle techniques of three attending
      surgeons. Among these reductions, 215 had complete records and were included in
      the data analysis. The remaining 64 records were evaluated for viability of the
      nipple-areola complex. Assessments included skin pattern markings, average size
      of reduction, average body mass index, and complications. Risk factors and
      patient comorbidities were also recorded. RESULTS: There were no cases of nipple
      loss in the series. The overall complication rate was 18 percent; patients'
      average body mass index was 29. The revision rate for contour or scar improvement
      was 4 percent. A statistically significant reduction in operating time of 41
      minutes (p = 0.0001) was seen in comparison with the inferior pedicle reduction.
      CONCLUSIONS: The superomedial dermoglandular pedicle is a safe and reliable
      technique for reduction mammaplasty. Its versatility allows for reproducible
      results in a broad range of patients with various skin excision patterns. Use of
      the superomedial pedicle provides consistent results with respect to breast
      contour, nipple viability, and lasting superomedial fullness, and saves operating
      time compared with the inferior pedicle technique.

PMID- 18040176
TI  - Immediate postoperative complications in DIEP versus free/muscle-sparing TRAM
      flaps.
AB  - BACKGROUND: The deep inferior epigastric perforator (DIEP) flap is a major
      advance in breast reconstruction, but many surgeons are reluctant to use it
      because of concerns about a higher flap loss rate when compared with free/muscle
      sparing transverse rectus abdominis myocutaneous (TRAM) flaps. Previous studies,
      however, have not statistically analyzed the relationship of patient
      characteristics to outcome. This study evaluates the authors' institutional
      experience with immediate postoperative complications following DIEP and
      free/muscle-sparing TRAM flaps. METHODS: Results of 200 consecutive free/muscle
      sparing TRAM and DIEP flaps performed by two surgeons at a single institution
      between 2003 and 2005 were reviewed using a prospectively maintained database.
      The incidence of flap complications was compared. Patient demographics, procedure
      type, diagnosis, adjuvant treatment, and complications were recorded. Outcome
      variables included total and partial flap loss, infection, seroma, hematoma,
      wound-healing problems, fat necrosis, and mastectomy flap necrosis. RESULTS: One
      hundred forty-three patients were treated with 159 free/muscle-sparing TRAM flaps
      and 41 DIEP flaps. The demographics of the two groups were statistically similar.
      No statistically significant differences were noted in total or partial flap
      loss. CONCLUSIONS: In the authors' series, the use of the DIEP flap did not
      result in more postoperative flap-related complications when compared with the
      free/muscle-sparing TRAM flap. Furthermore, no patient characteristics were
      statistically associated with a more successful result. The authors conclude that
      in patients whose anatomy reveals perforators of adequate size, the DIEP flap is
      a safe and reliable procedure for breast reconstruction.

PMID- 18040177
TI  - Correction of inverted nipples by strong suspension with areola-based dermal
      flaps.

PMID- 18040178
TI  - Norian craniofacial repair system: compatibility with resorbable and
      nonresorbable plating materials.
AB  - BACKGROUND: Choice of bone replacement materials is important when reconstructing
      large craniofacial defects. Hydroxyapatite cements are often used for such
      reconstructions. Recent advances in the development of these cements have
      produced locally applied, in situ hardening materials excellent for use in
      craniofacial defects. To date, there has been a paucity of data comparing the use
      of calcium phosphate cements in combination with titanium or resorbable plating
      systems and their combined biocompatibility. An experimental dog model was used
      to compare these systems. METHODS: Two 4 x 4-cm calvarial defects were created in
      each of 18 mongrel dogs, and defects were reconstructed with calcium phosphate
      cement with either titanium or resorbable mesh sheets to evaluate their
      interaction. Specimens were harvested and evaluated histologically for the
      development of new bone formation at 3, 6, and 12 months. RESULTS: At 3 months,
      no differences were noted in the amount of bone formed between titanium and
      resorbable plating. By 6 months, the resorbable mesh sheet showed delayed bone
      formation compared with the titanium mesh. At 12 months, bone formation over the
      resorbable mesh accelerated to be no different from the titanium mesh.
      Importantly, new bone formation was seen within the monocalcium phosphate cement
      Norian Craniofacial Repair System on a reliable basis, regardless of mesh plate
      used. CONCLUSIONS: There are no long-term adverse effects with the use of Norian
      cement with either titanium or resorbable mesh. However, further studies need to
      be conducted to determine why there is an arrested healing phase between 3 and 6
      months with the Norian cement and resorbable plating materials.

PMID- 18040179
TI  - Experimental animal model proving the benefit of primary defatting of full
      thickness random-pattern skin flaps by suppressing "perfusion steal".
AB  - BACKGROUND: The value of primary flap defatting remains unclear. This
      experimental animal study provides a novel theory on the problem of primary
      defatting, "steal of perfusion" to the skin by fat. This theory is based on the
      fact that the fat brings blood supply to the proximal flap portion but blood is
      sequestered in the fat of the distal flap portion, to the disadvantage of skin
      perfusion. METHODS: Fifteen full-thickness random-pattern skin flaps, with a 3:1
      length-to-width ratio, elevated on the necks of pigs and then left in situ on a
      plastic sheet interposed between the flap and the deep vascularization from the
      muscle, were compared with 15 identical contralateral flaps, defatted in the
      distal half. RESULTS: In the 15 nondefatted flaps, necrosis of the distal half of
      the flap was observed. Among the 15 defatted flaps, no necrosis was observed in
      four defatted flaps, partial necrosis was seen in five defatted flaps, concentric
      necrosis in three defatted flaps, partial necrosis in two defatted flaps, and
      necrosis in one defatted flap. Necrosis in defatted flaps was significantly less
      than that in nondefatted flaps (25.6 +/- 21.8 percent of flap surface versus 50
      +/- 2.7 percent; p < 0.001). CONCLUSIONS: There is a benefit to primary
      defatting. Perfusion steal exists for pedicular and peripheral vascularization.
      Primary partial defatting of a random-pattern flap is beneficial for distal
      perfusion, which is attributed to suppression of perfusion steal. Complete
      defatting is detrimental to flap survival. The fat is indispensable for perfusion
      of the proximal flap portion and is paradoxically detrimental for the distal
      region.

PMID- 18040180
TI  - rhBMP-4 gene therapy in a juvenile canine alveolar defect model.
AB  - BACKGROUND: Autologous bone grafts have the disadvantages of donor-site pain and
      morbidity, finite supply, increased costs, and prolonged hospitalizations. Using
      a juvenile canine model, the authors hypothesized that recombinant human (rh)
      bone morphogenetic protein (BMP)-4 gene therapy-treated alveolar defects would
      promote bone healing and canine tooth eruption equal to their autografted
      counterparts. METHODS: Sixty-five maxillary alveolar defects were created in
      juvenile foxhound dogs with a mean age of 80.8 days. Nineteen defects were
      treated with DNA plasmid encoding rhBMP-4, 16 defects were autografted, 15
      defects contained scaffold only, and 15 defects were left unrepaired. At 4 and 12
      weeks after surgery, bone density and tooth eruption were measured, respectively.
      Data were subjected to one-way analysis of variance testing with statistical
      significance established at p < 0.05. RESULTS: At 4 weeks, the bone densities in
      the rhBMP-4, autografted, scaffold-only, and defect-only groups were 31.2 +/-
      6.5, 30.5 +/- 8.1, 18.4 +/- 3.8, and 15.2 +/- 4.0 percent, respectively. A
      significant effect (p < 0.05) was observed between the rhBMP-4 gene therapy
      treated and autografted groups compared with the scaffold-only and defect-only
      groups. At 12 weeks, the rates of tooth eruption measured in the rhBMP-4,
      autografted, scaffold-only, and defect-only groups were 67.4 +/- 15.8, 58.3 +/-
      18.8, 52.7 +/- 16.2, and 45.0 +/- 13.3 percent, respectively. A significant
      effect (p < 0.05) was observed between the rhBMP-4 gene therapy-treated and
      defect-only groups. CONCLUSIONS: In the present studies, rhBMP-4 gene therapy was
      equivalent to autografting and superior to the scaffold-only and unrepaired
      defect in bone regeneration and tooth eruption. With decreased morbidity and
      cost, rhBMP-4 gene therapy may ultimately become an alternative to autografting
      to repair bony defects.

PMID- 18040181
TI  - Influences of preservation at various temperatures on liposuction aspirates.
AB  - BACKGROUND: Aspirated fat is not only a filler material but also an abundant
      source of adipose-derived stem cells. The aim of this study was to assess
      degeneration of aspirated fat during preservation and optimize the preservation
      method for lipoaspirates. METHODS: Aspirated fat was preserved at room
      temperature for 1, 2, 4, and 24 hours (n = 10 each); at 4 degrees C for 1, 2, and
      3 days (n = 14 each); or at -80 degrees C for 1 month (n = 3). Morphologic
      changes were assessed with scanning electron microscopy. Adipose-derived stem
      cell yield was measured after 1 week of culture. For aspirated fat preserved at
      room temperature, damaged adipocytes were assessed by measuring the oil volume
      ratio after centrifugation (n = 6) and glycerol-3-phosphate-dehydrogenase
      activity in washing solution (n = 4). Cell surface marker expression was examined
      by flow cytometry (n = 3). RESULTS: Although the scanning electron microscopic
      assay indicated no remarkable anatomical changes based on preservation methods,
      oil volume significantly increased in fat preserved at room temperature for 4
      hours. Adipose-derived stem cell yield was significantly reduced by preservation
      at room temperature for 24 hours and by preservation at 4 degrees C for 2 or 3
      days. Flow cytometric analysis suggested that the biological properties of
      adipose-derived stem cells did not significantly change at 4 degrees C up to 3
      days. The cells were isolated from cryopreserved fat, but the yield was much less
      than that from fresh aspirated fat. CONCLUSIONS: Aspirated fat should be
      transplanted as quickly as possible if it is preserved at room temperature. For
      adipose-derived stem cell isolation, aspirated fat can be stored or transported
      overnight if it is preserved at 4 degrees C without adipose-derived stem cell
      yield loss or changes in biological properties.

PMID- 18040182
TI  - Impact of the SMAS on Frey's syndrome after parotid surgery: a prospective, long
      term study.
AB  - BACKGROUND: Clinical observations indicate that creation of the superficial
      musculoaponeurotic system (SMAS) flap during parotid surgery decreases
      postoperative gustatory sweating (Frey's syndrome) and improves cosmesis after
      surgery. METHODS: On the basis of their previous study with 23 patients where no
      SMAS flap was used, the authors performed a prospective, long-term study of
      6(1/2) years in 25 patients, using the SMAS flap, and compared these results with
      the postoperative results of their initial study. Twenty-two patients of the SMAS
      flap group were available for reassessment of gustatory sweating and symptoms.
      The Minor starch test was used to document the extent and intensity of
      postoperative sweating. Satisfaction with postoperative cosmetic results was
      assessed through a semiquantitative questionnaire as used in the previous study.
      RESULTS: The incidence of symptomatic Frey's syndrome was significantly higher in
      the no-SMAS flap group after 23 months (43 percent versus 0 percent; p = 0.003).
      The surface extent of Frey's syndrome after 23 months was significantly reduced
      in the SMAS flap group (p = 0.006). At final follow-up, the incidence and extent
      of symptomatic Frey's syndrome showed no significant differences between the two
      groups (41 percent versus 56 percent; p = 0.42). The rate of satisfactory
      cosmetic results was significantly higher in the SMAS flap group (96 percent
      versus 35 percent; p < 0.05). CONCLUSIONS: Creation of the SMAS flap in parotid
      surgery for benign lesions delays the onset and reduces the intensity and extent,
      but does not prevent the occurrence, of Frey's syndrome. It reliably improves the
      cosmetic results by reducing the retromandibular depression after parotid
      surgery.

PMID- 18040183
TI  - Reconstruction of postburn neck contractures using free thin thoracodorsal artery
      perforator flaps with cervicoplasty.
AB  - BACKGROUND: Severe postburn neck contractures are devastating functional and
      cosmetic deformities. The ideal material for coverage of defects created by neck
      contracture release is thin, supple, large, well-vascularized, healthy tissue.
      The thoracodorsal artery perforator flap, a workhorse flap for reconstruction,
      allows a large dimension and free thickness control with low donor-site
      morbidity. The value of a free thin thoracodorsal artery perforator flap for
      anterior neck burn deformities has not been evaluated in a substantial series.
      METHODS: Four men and eight women underwent neck reconstruction from December of
      2002 to August of 2004. Mean patient age was 34.3 years (range, 21 to 47 years).
      Thorough burn scar contracture releases were performed and cervicoplasty was
      added for optimal neck appearance. Uniformly thin thoracodorsal artery perforator
      flaps were made. Both lateral ends of these flaps were designed with a fishtail
      shape for sufficient release and to minimize linear scar band formation in the
      most lateral region of the neck. RESULTS: Elevated flaps as large as 24 x 12 cm
      and with a mean thickness 5.3 mm were used. All flaps survived without
      significant complications. Range of neck motion increased, and the
      cervicomandibular angle was sharpened in all patients. A highly natural neck
      contour was universally obtained without a secondary debulking procedure.
      CONCLUSIONS: The free thin thoracodorsal artery perforator flap with
      cervicoplasty provides good functional and aesthetic results in terms of neck
      contour and cervicomental angle, with a reduced necessity for secondary
      procedures and low donor-site morbidity. This method is highly valuable for
      reconstruction of severe postburn neck contractures.

PMID- 18040184
TI  - A face lift approach for sentinel node biopsy in head and neck melanoma patients.
AB  - BACKGROUND: Management of head and neck melanoma has changed dramatically with
      the use of sentinel node biopsy for staging. Nodal dissection may now be delayed
      or deferred based on the results of the sentinel node biopsy. The authors suggest
      using a face lift incision to access the nodal basins for sentinel node biopsy in
      head and neck melanoma. METHODS: A face lift incision was used successfully for
      sentinel node biopsy in 21 patients. The diagnosis of melanoma, histologic
      subtype, and depth of penetration were established by biopsy with permanent
      sections. All patients underwent lymphoscintigraphy on the morning of their
      surgery. If the scan showed multiple nodes at various levels of the neck or
      parotid, the patient was selected for a face lift incision for biopsy. RESULTS:
      The study comprised 14 men and seven women between the ages of 26 and 82 years
      (mean age, 55 years). The sites of melanoma included the temple in six patients,
      cheek in five, neck in four, and ear and scalp in two patients each. The average
      Clark's level and Breslow depth were 3.67 and 1.76 mm, respectively. The average
      number of basins involved was 2.14; the average number of nodes was 3.33, with an
      average of 1.56 nodes per basin. Follow-up ranged from 2 to 53 months (average,
      26 months). Only two patients had sentinel nodes that were positive for
      metastatic melanoma. One complication, a transient paresis of the right marginal
      mandibular nerve, was observed. CONCLUSIONS: Using a face lift incision for
      sentinel node biopsy in head and neck melanoma is a safe, reliable technique. It
      provides excellent access to multiple nodal basins, well-concealed incisions,
      wide exposure for delayed therapeutic nodal dissection, and local and regional
      flap options for reconstructing the excision site.

PMID- 18040185
TI  - Anatomical and technical aspects of harvesting the auricle as a neurovascular
      facial subunit transplant in humans.
AB  - BACKGROUND: Auricular transplants from cadaveric sources may be a viable
      alternative for difficult auricular reconstruction once immunologic problems are
      largely solved. The authors report on the neurovascular anatomy and technical
      details of harvesting the auricle as a single facial subunit. METHODS: Nine
      auricles were studied in latex-injected (n = 5) and fresh cadaveric heads (n =
      4). In latex-injected heads, dissection in the neck and auricular region and
      microdissection within the substance of the auricle were performed under loupe
      magnification. The arterial network was exposed and measurements were taken,
      including the size, length, and diameters of vessels. The number of branches
      supplying the entire auricle was noted. Methylene blue dye was injected into
      fresh cadaveric heads through the posterior auricular (n = 2) or superficial
      temporal arteries (n = 2) to assess the territory supplied by each arterial
      system. RESULTS: Dye injected into the superficial temporal artery stained the
      upper two-thirds of the anterior and posterior auricular regions; all anterior
      cartilaginous eminences, except the antitragus, were homogenously stained. Dye
      injected into the posterior auricular artery stained the lobule, posterior
      auricular skin, and the depressed anterior auricular regions, including the cavum
      conchae, scapha, and triangular fossa. Neither the superficial temporal nor the
      posterior auricular arteries could adequately nourish the entire auricle as
      single pedicles. The auriculotemporal and great auricular nerves can be included
      in the transplant for sensation. The temporoparietal scalp can also be reliably
      included to meet reconstructive requirements. CONCLUSIONS: The auricle can be
      reliably elevated as a transplant when nourished by both the superficial temporal
      and posterior auricular arterial systems. The external jugular vein and external
      carotid artery can therefore be used as the vascular pedicle for auricular
      transplantation.

PMID- 18040186
TI  - Measuring sensibility of the trigeminal nerve.

PMID- 18040187
TI  - The superior and inferior gluteal artery perforator flaps.
AB  - BACKGROUND: Perforator flaps have allowed reconstruction of soft-tissue defects
      throughout the body. The superior and inferior gluteal artery perforator flaps
      have been used clinically, yet the published anatomical studies describing the
      blood supply to the gluteal skin are inadequate. This study comprehensively
      evaluated the anatomical basis of these flaps to present anatomical landmarks to
      facilitate flap dissection. METHODS: In six fresh cadavers, the integument of the
      gluteal region was dissected. Cutaneous perforators of the superior and inferior
      gluteal arteries were identified. Their course, size, location, and type
      (septocutaneous versus musculocutaneous) were recorded based on dissection,
      angiography, and photography. The surface areas of cutaneous territories and
      perforator zones were measured and calculated. RESULTS: The average number of
      superior and inferior cutaneous perforators greater than or equal to 0.5 mm in
      the gluteal region was 5 +/- 2 and 8 +/- 4, respectively, with all of the
      superior and 99 percent of the inferior gluteal artery perforators being
      musculocutaneous. Their average perforator internal diameter was 0.6 +/- 0.1 mm.
      The average superior and inferior gluteal artery cutaneous vascular territory was
      69 +/- 56 cm and 177 +/- 38 cm, respectively. The superior gluteal perforators
      were found adjacent to the medial two-thirds of a line drawn from the posterior
      superior iliac spine to the greater trochanter. The inferior gluteal artery
      perforators were concentrated along a line in the middle third of the gluteal
      region above the gluteal crease. CONCLUSION: The reliable size and consistency of
      the superior and inferior gluteal artery perforators allow the use of pedicled
      and free superior and inferior gluteal artery perforator flaps in a variety of
      clinical situations.

PMID- 18040189
TI  - Treatment of giant omphalocele with intraabdominal tissue expansion.

PMID- 18040188
TI  - Resumption of sexual activity after plastic surgery: current practice and
      recommendations.
AB  - BACKGROUND: Information on sexual counseling and practice guidelines after
      plastic surgery is quite limited and poorly documented as part of clinical care
      after surgery. The aim of this study was to assess board-certified plastic
      surgeons' current practices and to make clinical recommendations for resumption
      of sexual activity in the postoperative period. METHODS: A descriptive mailed
      survey of randomly chosen American Society of Plastic Surgeons' members was
      designed to evaluate plastic surgeons' methods of screening for sexual concerns,
      the frequency of postoperative discussions with patients, and clinical
      recommendations for safe sexual positions. RESULTS: There were 281 respondents,
      for a response rate of 40 percent. A minority of plastic surgeons (32.9 percent)
      felt it was the surgeon's role to provide postoperative sexual counseling
      regarding restrictions and guidelines; the majority of plastic surgeons (63
      percent) felt that their nurse should provide this service. Patients never (46.6
      percent) or rarely (23.8 percent) asked about sexual activity restrictions after
      surgery. Some surgeons (27.8 percent) proactively discussed postoperative sexual
      activity, but 57.3 percent said they rarely or never gave specific advice. There
      were gender differences; male plastic surgeons discussed specific sexual
      techniques and positions significantly more frequently than female plastic
      surgeons (p = 0.001), and patients ask male plastic surgeons significantly more
      frequently about sexual activity restrictions than they do female plastic
      surgeons (p = 0.001). CONCLUSIONS: Many plastic surgeons gave little or no advice
      to patients regarding resumption of sexual activity after surgery, and the
      majority of patients do not initiate the discussion. Most surgeons expect their
      nursing staff to provide sexual counseling.

PMID- 18040190
TI  - Outcome of simultaneous and staged microvascular free tissue transfer connected
      to arteriovenous loops in areas lacking recipient vessels.
AB  - BACKGROUND: Arteriovenous loops are an indispensable tool in free flap surgery
      when appropriate recipient vessels are missing. In this study, the authors
      analyzed whether the outcome differs when flaps were transferred simultaneously
      or subsequently after construction of arteriovenous loops. METHODS: Twenty-seven
      patients requiring free tissue transfer received arteriovenous loops by pedicled
      or free vein grafts because of inadequate local recipient vessels. In head and
      neck reconstruction, pedicled brachiocephalic or free saphenous vein grafts were
      anastomosed to cervical or axillary vessels. Pedicled major saphenous vein grafts
      were used in the pelvic area whereas, in lower leg and foot reconstruction, free
      saphenous or brachiocephalic veins were used. Flaps were transferred
      simultaneously (n = 10) or 4 to 17 days later (n = 17). RESULTS: Thrombosis
      required revision in staged transfer (n = 3 patients) or in simultaneous flap
      transfer (n = 2). No free flap was lost. Fisher's exact test did not indicate a
      significant difference between a simultaneous or staged flap transfer.
      CONCLUSIONS: Temporary arteriovenous loops provide adequate recipient vessels and
      flow to supply microvascular free flap tissue transfer in areas lacking recipient
      vessels and in which no other reconstructive options exists. No statistical
      differences in complications and overall outcome were found between immediate or
      secondary free tissue transfer. Meticulous monitoring of microvascular perfusion,
      however, is mandatory in both approaches and early intervention is necessary to
      ensure successful tissue transfer.

PMID- 18040191
TI  - Use of the soleus musculocutaneous perforator for skin paddle salvage of the
      fibula osteoseptocutaneous flap: anatomical study and clinical confirmation.
AB  - BACKGROUND: The skin paddle of the fibula osteoseptocutaneous flap is reliably
      vascularized by septocutaneous perforators from the peroneal artery. However, in
      5 to 10 percent of lower limbs, these perforators are absent. This anatomical
      study evaluated use of the soleus musculocutaneous perforator for skin paddle
      salvage in such situations. METHODS: Latex injection studies were performed on 20
      cadaveric lower limbs. The presence, prevalence, and location of the
      musculocutaneous perforators in the distal leg were documented. The perforators
      were traced proximally to determine their origins. RESULTS: Of the 20 cadaveric
      limbs, one or more musculocutaneous perforators of at least 0.5 mm in diameter
      were noted in 18 specimens (90 percent). They were located within 6 cm of the
      junction of the middle and lower thirds of the fibula. The soleus
      musculocutaneous perforators originated in the peroneal artery in 10 specimens
      (50 percent), the posterior tibial artery in seven (35 percent), and the
      tibioperoneal trunk in one (5 percent). This information was successfully used to
      salvage the skin paddle in two of our clinical cases. CONCLUSIONS: Use of the
      soleus musculocutaneous perforator depends on its origin. When it arises from the
      peroneal artery, a single set of anastomoses is all that is necessary for flap
      revascularization, with the skin paddle serving as a monitor for the bone flap.
      When it originates from the posterior tibial artery or tibioperoneal trunk, a
      second set of anastomoses is needed and the skin paddle cannot monitor the bone
      flap. The authors propose that one or two soleus musculocutaneous perforators be
      preserved during harvest until existence of the septocutaneous perforator is
      confirmed.

PMID- 18040192
TI  - Evaluation of elbow flexion as a predictor of outcome in obstetrical brachial
      plexus palsy.
AB  - BACKGROUND: The purpose of this study was to answer two questions. First, are
      there obstetrical brachial plexus palsy patients with no elbow flexion at 3
      months who go on to recover useful upper extremity function without surgical
      intervention? Second, are there patients with evidence of elbow flexion at 3
      months who do benefit from brachial plexus reconstruction? METHODS: The authors
      retrospectively reviewed a sample drawn from 253 consecutive patients at The
      Hospital for Sick Children obstetrical brachial plexus database from 1993 to
      1996. Inclusion criteria were examination at age 3 months and either complete
      spontaneous recovery or repeated examination after age 3 years. Two hundred nine
      patients satisfied the inclusion criteria. Patients were distributed into four
      groups: group A, no elbow flexion at age 3 months (operative management); group
      B, elbow flexion present at 3 months (operative management); group C, no elbow
      flexion at age 3 months (nonoperative management); and group D, elbow flexion
      present at 3 months (nonoperative management). RESULTS: Groups A, B, and C showed
      significant intragroup improvements in both elbow flexion (p < 0.0001) and total
      limb motion scores (the sum of 15 individual joint motions) (p < 0.0001) with
      time. No differences were noted among groups A, B, and C for either elbow flexion
      or total limb motion scores at final follow-up. CONCLUSIONS: Early elbow flexion
      alone is not a sufficient criterion to recommend a nonoperative approach. In
      addition, spontaneous recovery of useful upper extremity function has been
      observed in a carefully selected subset of patients without elbow flexion at 3
      months.

PMID- 18040193
TI  - Intravenous regional anesthesia administered by the operating plastic surgeon: is
      it safe and efficient? Experience of a medical center.
AB  - BACKGROUND: Intravenous regional anesthesia (Bier's block) is an effective method
      of providing anesthesia for extremity surgery. This technique is most suitable
      for short-duration, less than 60-minute surgical procedures in distal
      extremities. Earlier studies recommended that intravenous regional anesthesia be
      performed by anesthesiologists who are familiar with the technique and fully
      trained to treat its complications. This study was conducted to demonstrate that
      intravenous regional anesthesia administered by the operating plastic surgeon is
      safe, efficient, and simple to perform. METHODS: A 5-year retrospective chart
      review (January of 2000 to December of 2004) was undertaken. The study included
      patients who underwent surgical procedures and were administered intravenous
      regional anesthesia by the surgeon. RESULTS: Four hundred forty-eight patients
      were included in the study, and 479 operations of 483 scheduled were completed
      under intravenous regional anesthesia performed by the operating surgeon.
      Intravenous regional anesthesia was efficient in 478 of 479 of the cases (99.8
      percent). Tourniquet-related technical problems were noted in five of 483 cases
      (1 percent), resulting in cancellation of four operations, with no reported
      consequent anesthetic toxicity. Minor complications were reported in six of 479
      of the cases (1.2. percent). No major complications occurred. CONCLUSIONS:
      Despite earlier worries about the safety of intravenous regional anesthesia if
      not administered by anesthesiologists, the authors found that intravenous
      regional anesthesia represents a safe and efficient technique of anesthesia for
      extremity surgery when performed carefully and appropriately by the operating
      surgeon. The authors suggest that plastic surgeons familiarize themselves with
      this technique, which is simple to perform. This could probably result in lower
      overall costs and greater autonomy for the surgeon.

PMID- 18040194
TI  - Hand evaluation following ulnar forearm perforator flap harvest: a prospective
      study.

PMID- 18040195
TI  - Primary grafting with autologous cranial particulate bone prevents osseous
      defects following fronto-orbital advancement.
AB  - BACKGROUND: Approximately 20 percent of patients require cranioplasty for defects
      after fronto-orbital advancement. The authors hypothesized that corticocancellous
      cranial particulate bone placed over exposed dura at the time of fronto-orbital
      advancement would decrease the frequency of incomplete ossification. METHODS: The
      authors retrospectively analyzed consecutive children who underwent fronto
      orbital advancement for craniosynostosis between 1988 and 2006. In group I,
      cranial gaps resulting from frontal advancement were left open and allowed to
      heal spontaneously. In group II, corticocancellous particulate bone was used to
      fill the calvarial defects. Bone was harvested from the endocortex of the frontal
      segments or parietal calvaria using a hand-driven brace and bit. Outcome
      variables were persistent osseous defects and need for corrective cranioplasty.
      RESULTS: The study included 213 children. There were 50 patients in group I: mean
      age at fronto-orbital advancement was 7.0 months (range, 2 to 15 months); 12
      patients (24 percent) had residual defects and 10 (20 percent) required
      cranioplasty. Group II contained 163 patients: mean age at fronto-orbital
      advancement was 14.1 months (range, 6 to 72 months); nine children (5.5 percent)
      had a cranial defect and five (3.1 percent) required cranioplasty. Infants in
      group II were less likely to have bony defects (p = 0.0005) or require
      cranioplasty (p = 0.0002) compared with children in group I, despite being older
      at the time of fronto-orbital advancement (p = 0.001). CONCLUSION:
      Corticocancellous cranial particulate bone grafting during fronto-orbital
      advancement reduces the prevalence of osseous defects and the need for secondary
      cranioplasty, independent of patient age.

PMID- 18040196
TI  - Evaluation of cleft lip bony depression of piriform margin and nasal deformity
      with cone beam computed tomography: "retruded-like" appearance and
      anteroposterior position of the alar base.
AB  - BACKGROUND: As the nasal platform, the piriform margin is considered the most
      important nasal structure. An insufficient bony structure has been suggested to
      be the major factor in secondary nasal deformities such as the "depressed alar
      base." It is unclear, however, how the piriform margin is depressed or how bony
      depression influences nasal shape. METHODS: Using cone beam computed tomography,
      the anteroposterior positions of the cleft-side piriform margin and alar base
      were compared with those of the noncleft side in 52 postoperative unilateral
      cleft lip patients with no alveolar bone graft. Patients were divided based on
      cleft type into either the unilateral cleft lip, alveolus, and palate group or
      the unilateral cleft lip and alveolus group. RESULTS: In all cases, the cleft
      side piriform margin was depressed. The anteroposterior position of the alar base
      was related to the piriform depression in both groups. However, in contrast with
      bony depression, the cleft-side alar base was located more anteriorly than the
      non-cleft-side alar base in 35 of 52 patients. CONCLUSIONS: The authors' study
      suggests that bony depression does not necessarily lead to postoperative alar
      depression. The postoperative cleft lip alar position can be maintained
      independently of the collapsed lesser segment of the maxilla. In addition, in
      many cleft lip newborns the cleft alar crease is hypoplastic, and the paranasal
      triangle is easily elevated by operative manipulation because of the muscular
      dysfunction. This shallowness leads to a "retruded" appearance. For improvement,
      preservation of the paranasal triangle and alar crease plasty are important.

PMID- 18040197
TI  - Midterm follow-up of midface distraction for syndromic craniosynostosis: a
      clinical and cephalometric study.
AB  - BACKGROUND: The authors studied the effect of midface distraction on maxillary
      skeletal position and clinical appearance in patients with Crouzon, Pfeiffer, and
      Apert syndromes, and examined the stability of these changes at 1 year after
      distraction. METHODS: Fifteen consecutive patients (six male and nine female;
      average age, 5.9 years) underwent Le Fort III osteotomy with midface advancement
      using a rigid external distraction device. Six patients had Crouzon, five had
      Pfeiffer, and four had Apert syndrome. Midface advancement was initiated at the
      level of the occlusal splint and at the zygomatic/maxillary anchor screws. The
      device was activated 11 mm on average, at a rate of 1 mm per day. Twenty
      anatomical landmarks were identified and digitized at three time intervals, and
      displacement of each landmark was compared with its pretreatment position.
      RESULTS: By the time of device removal, point A had advanced sagittally along the
      x axis 15.85 mm and moved downward 1.06 mm along the y axis; the orbitale was
      moved sagittally along the x axis 12.72 mm and downward 1.99 mm along the y axis.
      Maximum mean advancement (17.16 mm) was observed at the upper incisal edge.
      Maxillary and mandibular skeletal discrepancy was significantly decreased, with
      the ANB angle changing from -5.87 to +13.17 degrees. At 1 year after distraction,
      point A had advanced an additional 0.81 mm, and the orbitale and upper incisal
      edge had moved posteriorly 0.07 mm and 1.34 mm, respectively. CONCLUSION:
      Significant midface advancement can be achieved and maintained with rigid
      external distraction of the Le Fort III osteotomy segment (up to 24 mm), with
      excellent stability of the advanced midfacial skeleton.

PMID- 18040198
TI  - The septospinal ligament in cleft lip nose deformity: study in adult unilateral
      clefts.
AB  - BACKGROUND: Septal deviation and alar cartilage deformities constitute an
      important component of both the aesthetic deformity and airway compromise in
      unilateral cleft lip nose deformity. The purpose of this study was to examine the
      retrocolumellar preseptal area in this deformity for evaluation of deforming
      forces in the adult population. METHODS: Fifty-five patients aged 13 years or
      older presenting with unilateral cleft nasal deformity were included. The caudal
      border of the septum was accessed using an incision along the ipsilateral
      membranous septum. Perioperatively, the curved caudal septal edge was exposed and
      explored down to its attachment with the hypertrophied anterior nasal spine. The
      overlying tethering tissues were excised and submitted for histopathologic
      examination. The curved septal cartilage was straightened and the misplaced
      anterior nasal spine was excised. The remaining cleft nasal deformity was
      corrected depending on the specific presenting pathologic abnormality. RESULTS: A
      well-defined, tough, fibrous band was detected extending from the deviated curved
      surface of the septal cartilage to the anterior nasal spine that was filling up
      the retrocolumellar area. Histopathologic examination revealed fibrous tissue in
      all cases studied, consistent with diagnosis of a ligament. Postoperatively, the
      nasal tip complex cosmetic result was considered to be good or very good in 89.7
      percent, satisfactory in 8.1 percent, and poor in 2.0 percent of patients.
      CONCLUSIONS: A well-defined ligament has been documented and demonstrated in
      adult patients with unilateral cleft lip nose deformity. The authors recommend
      that this septospinal ligament, previously unreported, should be excised in toto
      to achieve straightening of the septum, columellar centralization, and nasal sill
      symmetry in unilateral cleft lip nose deformity.

PMID- 18040199
TI  - A virtual reality atlas of craniofacial anatomy.
AB  - BACKGROUND: Head and neck anatomy is complex and represents an educational
      challenge to the student. Conventional two-dimensional illustrations inherently
      fall short in conveying intricate anatomical relationships that exist in three
      dimensions. A gratis three-dimensional virtual reality atlas of craniofacial
      anatomy is presented in an effort to address the paucity of readily accessible
      and customizable three-dimensional educational material available to the student
      of head and neck anatomy. METHODS: Three-dimensional model construction was
      performed in Alias Maya 4.5 and 6.0. A basic three-dimensional skull model was
      altered to include surgical landmarks and proportions. Some of the soft tissues
      were adapted from previous work, whereas others were constructed de novo.
      Texturing was completed with Adobe Photoshop 7.0 and Maya. The Internet
      application was designed in Viewpoint Enliven 1.0. RESULTS: A three-dimensional
      computer model of craniofacial anatomy (bone and soft tissue) was completed. The
      model is compatible with many software packages and can be accessed by means of
      the Internet or downloaded to a personal computer. As the three-dimensional
      meshes are publicly available, they can be extensively manipulated by the user,
      even at the polygonal level. CONCLUSIONS: Three-dimensional computer graphics has
      yet to be fully exploited for head and neck anatomy education. In this context,
      the authors present a publicly available computer model of craniofacial anatomy.
      This model may also find applications beyond clinical medicine. The model can be
      accessed gratis at the Plastic and Reconstructive Surgery Web site or obtained as
      a three-dimensional mesh, also gratis, by contacting the authors.

PMID- 18040200
TI  - Anatomy of the corrugator supercilii muscle: part I. Corrugator topography.
AB  - BACKGROUND: Complete corrugator supercilii muscle resection is important for the
      surgical treatment of migraine headaches and may help prevent postoperative
      abnormalities in surgical forehead rejuvenation. Specific topographic analysis of
      corrugator supercilii muscle dimensions and its detailed association with the
      supraorbital nerve branching patterns has not been thoroughly delineated. Part I
      of this two-part study aims to define corrugator supercilii muscle topography
      with respect to external bony landmarks. METHODS: Twenty-five fresh cadaver heads
      (50 corrugator supercilii muscles and 50 supraorbital nerves) were dissected to
      isolate the corrugator supercilii muscle from surrounding muscles. Standardized
      measurements of corrugator supercilii muscle dimensions were taken with respect
      to the nasion and lateral orbital rim. RESULTS: Relative to the nasion, the most
      medial origin of the corrugator supercilii muscle was found at 2.9 +/- 1.0 mm;
      the most lateral origin point, 14.0 +/- 2.8 mm. The lateralmost insertion of the
      corrugator supercilii muscle measured 43.3 +/- 2.9 mm from the nasion or 7.6 +/-
      2.7 mm medial to the lateral orbital rim. The most cephalic extent (apex) of the
      muscle was located 32.6 +/- 3.1 mm cephalad to the nasion-lateral orbital rim
      plane and 18.0 +/- 3.7 mm medial to the lateral orbital rim. There were no
      statistical differences noted between the right and left sides. CONCLUSIONS: The
      dimensions of the corrugator supercilii muscle are more extensive than previously
      described and can be easily delineated using fixed bony landmarks. These data may
      prove beneficial in performing safe, complete, and symmetric corrugator
      supercilii muscle resection for forehead rejuvenation and for effective
      decompression of the supraorbital nerve and supratrochlear nerve branches in the
      surgical treatment of migraine headaches.

PMID- 18040201
TI  - Versatility of diced cartilage-fascia grafts in dorsal nasal augmentation.
AB  - BACKGROUND: Augmentation of the nasal dorsum using autologous cartilage remains
      an exacting task in rhinoplasty. Precise, long-term control over graft contour
      and alignment can be difficult to achieve. In an attempt to alleviate these
      problems, the use of diced cartilage wrapped in a supportive sleeve has recently
      seen a resurgence of interest. The Turkish delight technique uses Surgicel as the
      sleeve material, whereas Daniel and Calvert have proposed autologous fascia.
      METHODS: The objective of this study was to assess the efficacy and reliability
      of diced cartilage-fascia grafts in the treatment of dorsal nasal volume
      deficiencies. RESULTS: Over a 2-year period, 20 adult patients underwent nasal
      augmentation using diced cartilage-fascia grafts. The indications for dorsal
      grafting were congenital saddling, racial refinement, or iatrogenic or
      posttraumatic deformities. Apart from one infection, all of the hybrid grafts
      retained their original volume and had not undergone resorption by a mean time of
      16 months postoperatively. A critical analysis of the radix-dorsum aesthetics led
      to a minor modification of the original technique. CONCLUSION: This series
      supports the use of diced cartilage-fascia grafts for the correction of difficult
      dorsal nasal defects with grafting in the 3- to 5-mm range in primary and
      secondary rhinoplasty.

PMID- 18040203
TI  - The change of maximum bite force after botulinum toxin type a injection for
      treating masseteric hypertrophy.
AB  - BACKGROUND: A botulinum toxin type A injection into the masseter muscle has been
      used as a noninvasive treatment for masseteric hypertrophy. However, muscle
      atrophy inevitably causes a change of bite force. The aim of this study was to
      evaluate the change in the maximum bite force after a botulinum toxin type
      injection for the treatment of masseteric hypertrophy. METHODS: Seven patients
      who had presented for treatment of masseteric hypertrophy participated in this
      study. Twenty-five units of botulinum toxin type was injected into each masseter
      muscle, 50 units in total, at two to five points at the prominent portions of the
      mandibular angle. The bite-force measurement apparatus included a digital
      multimeter and a bite-force transducer. The maximum bite force between the
      maxillary and mandibular first molars was measured before injection and at 2, 4,
      8, and 12 weeks after injection. RESULTS: The difference in maximum bite force
      between the preinjection and 2-, 4-, and 8-week postinjection time points was
      statistically significant. However, there was no such difference between the
      preinjection and 12-week postinjection values (p < 0.05). CONCLUSIONS: The
      maximum bite force was significantly reduced after injection of botulinum toxin
      type A for the treatment of masseteric hypertrophy. However, it gradually
      recovered by 12 weeks.

PMID- 18040204
TI  - A comparison of face lift techniques in eight consecutive sets of identical
      twins.
AB  - BACKGROUND: Selecting the "correct" face lift technique has always been a
      difficult decision for the plastic surgeon. A technique that provides optimal
      aesthetics for one patient may not provide the same result for another. The
      complexity of comparing these different results on patients with different facial
      features further confounds one's ability to decide on a given technique. Even
      identical twins are often treated more appropriately with a different technique
      from one twin to the other because the character and severity of facial aging may
      differ between them. By comparing different superficial musculoaponeurotic system
      techniques on "less different" people (identical twins), perhaps the ideal
      technique may be determined. METHODS: Between November of 1997 and April of 1999,
      eight sets of twins underwent face lift surgery by the senior author (D.E.A.),
      using one of four techniques. The charts and photographs of the eight consecutive
      pairs of twins (16 patients) were reviewed retrospectively. RESULTS: No one face
      lift technique performed in this study produced a superior result as compared
      with another when performed on the appropriate patient. CONCLUSION: There exists
      no face lift technique suitable for every patient. As the current literature
      suggests, there is no one "best" face lift technique of those studied.

PMID- 18040205
TI  - One-stage mastopexy with breast augmentation: a review of 321 patients.
AB  - BACKGROUND: One-stage mastopexy with breast augmentation is an increasingly
      popular procedure among patients. In the past 9 years, there has been a 506
      percent increase in mastopexy procedures alone. Although some recommend a staged
      mastopexy and breast augmentation, there are currently no large studies
      evaluating the safety and efficacy of a one-stage procedure. METHODS: A
      retrospective chart review was conducted of 321 consecutive patients who
      underwent one-stage mastopexy and breast augmentation. Data collected included
      the following: patient characteristics, implant information, operative technique,
      and postoperative results. Complication and revision rates were calculated to
      evaluate the safety and efficacy of the one-stage procedure. RESULTS: No severe
      complications were recorded over an average of 40 months' follow-up. The most
      common complication was deflation of a saline implant (3.7 percent), followed by
      poor scarring (2.5 percent), recurrent ptosis (2.2 percent), and areola asymmetry
      (2.2 percent). Forty-seven patients (14.6 percent) underwent some form of
      revision surgery following the one-stage procedure. Thirty-five (10.9 percent) of
      these were for an implant-related issue, whereas 12 patients (3.7 percent)
      underwent a tissue-related revision. This 10.9 percent implant-related revision
      rate is less than a previously documented 13.2 percent 3-year reoperation rate
      for breast augmentation alone. The authors' 3.7 percent tissue-related revision
      rate also compares favorably to an 8.6 percent revision surgery rate in patients
      who underwent mastopexy alone. CONCLUSIONS: Although it has been stated that the
      risks of a one-stage procedure are more than additive, the results of our review
      suggest otherwise. Although a revision rate of 14.6 percent is significant, it is
      far from the 100 percent reoperation rate required for a staged procedure.

PMID- 18040206
TI  - The Brava external tissue expander: is breast enlargement without surgery a
      reality?
AB  - BACKGROUND: Controlled trials have shown that an external breast tissue expander
      (Brava; Brava LLC Miami, Fla.) can effectively enlarge the breast without
      surgery. However, satisfaction with the results has varied among doctors and
      patients. The first author critically evaluated her clinical experience with
      Brava and attempted to identify factors associated with a successful outcome.
      METHODS: Between May of 2003 and September of 2005, the first author supervised
      the treatment of 50 women. Volume measurements and standardized photographs of
      the breasts were obtained at the beginning of treatment and up to 12 months after
      treatment ended. At the final visit, women completed a satisfaction
      questionnaire. RESULTS: Forty women were evaluated at an average of 10 months
      after discontinuation of treatment (range, 7 to 20 months). Reasons for drop-out
      were noncompliance with the treatment (n = 6), unwillingness to attend follow-up
      visits (n = 3), and more than 5 percent body weight change (n = 1). The women
      used Brava 11 hours a day for a median period of 18.5 weeks (range, 14 to 52
      weeks). The median volume increase was 155 cc (range, 95 to 300 cc). Thirty women
      (75 percent) were satisfied or very satisfied with the results, five (12.5
      percent) acknowledged enlargement of their breasts but considered the treatment
      too bothersome, and five (12.5 percent) were disappointed because of little
      growth. Factors associated with poor growth included lesser intensity of wear (p
      < 0.002) and low body mass index (p = 0.055). CONCLUSIONS: Long-term breast
      enlargement without surgery is possible with an external tissue expander. The
      more it is used, the more the breasts grow. To avoid disappointments and drop
      outs, women have to be well informed about the time and lifestyle commitment.

PMID- 18040208
TI  - Back contouring in weight loss patients.
AB  - BACKGROUND: Body contouring in the post-bariatric surgery patient has focused
      predominantly on the resulting tissue excesses of the abdomen, breasts, and arms.
      The back, however, has not received the same attention and, although the skin
      folds on the back may sometimes be improved by addressing the previously
      mentioned areas, the result is usually unsatisfactory and leaves the patient with
      significant residual excess. METHODS: The senior author (B.S.) has developed a
      classification system and surgical treatment for the excess back tissue that
      eliminates these folds. RESULTS: Modifications of the senior author's techniques
      of mammaplasty/mastopexy and circumferential abdominoplasty, in addition to
      direct excision, are used to improve the contour of the back. CONCLUSIONS:
      Contouring of the back roll deformities seen in post-bariatric surgery patients
      requires a systematic approach. With this approach, the authors have been able to
      achieve uniform patient satisfaction with low morbidity. Although patients are
      left with additional scarring, this tradeoff is accepted by nearly all patients
      for the dramatic improvement in body contour.

PMID- 18040209
TI  - Endoscopic brow lift, upper and lower blepharoplasty, retinacular canthopexy:
      personal approach.

PMID- 18040210
TI  - Operating room fires: optimizing safety.
AB  - BACKGROUND: This prospective study was undertaken to determine the safest means
      of supplemental oxygen delivery for patients undergoing facial cosmetic surgery
      under conscious sedation. Two common methods of oxygen delivery were used in 20
      patients: (1) a nasal cannula and (2) a red rubber nasopharyngeal tube through
      which the cut ends of the nasal cannula were passed into the posterior pharynx.
      METHODS: The project was carried out in two parts. In part one, each subject was
      placed supine and oxygen supplementation at 3 liters/minute was applied through
      the nasal cannula. The oxygen concentration at 24 different set locations around
      the patient's face was analyzed using the random access mass spectrometer unit,
      starting at the right and left alar rim and then at 2-cm intervals laterally,
      superiorly, and inferiorly. The procedure in part one was repeated with oxygen
      being delivered by passing the cut cannula end through a red rubber
      nasopharyngeal tube into the posterior pharynx. RESULTS: Statistical analysis has
      showed that in all sites at or above the nasal area, the difference between the
      nasal cannula and red rubber nasopharyngeal tube is significantly greater than 0,
      indicating that higher concentrations are observed with the nasal cannula than
      with the red rubber nasopharyngeal tube (p = 0.004). CONCLUSION: The authors'
      study demonstrates a significant reduction in oxygen concentration, to levels
      consistent with ambient air, even at points extremely close to the oxygen source,
      when the nasopharyngeal tube system was used.

PMID- 18040211
TI  - 50th Anniversary Plastic Surgery Research Council Panel on the Future of Academic
      Plastic Surgery.

PMID- 18040212
TI  - Bridging the gap: the 34th Varaztad H. Kazanjian Memorial Lecture.

PMID- 18040213
TI  - The lagging U.S. Health care information technology infrastructure: parallel
      challenges for plastic surgery.

PMID- 18040214
TI  - Appropriate prophylactic antibiotic use in plastic surgery: the time has come.

PMID- 18040217
TI  - Putting wild maggots on your head is not "maggot therapy," but it does suggest
      pre-existing pathology.

PMID- 18040218
TI  - Maggot debridement therapy.

PMID- 18040221
TI  - Surgical treatment of partial defects of the external ear.

PMID- 18040223
TI  - Augmentation mentoplasty with diced high-density porous polyethylene.

PMID- 18040224
TI  - Medial epicanthoplasty using the skin redraping method.

PMID- 18040225
TI  - Securing nasal tip rotation through suspension suture technique.

PMID- 18040228
TI  - Anatomical study of factors contributing to zygomatic complex fracture
      instability in human cadavers.

PMID- 18040230
TI  - Minimally invasive surgery for the treatment of focal axillary hyperhidrosis.

PMID- 18040231
TI  - The double opposing periareola flap: a novel concept for nipple-areola
      reconstruction.

PMID- 18040233
TI  - Perforator-plus flaps or perforator-sparing flaps: different names, same concept.

PMID- 18040235
TI  - Iron toxicity as a potential factor in AMD.
AB  - While it has been known for years that iron overload is associated with retinal
      degeneration in the context of ocular siderosis, intraocular hemorrhage, and the
      hereditary diseases aceruloplasminemia and pantothenate kinase associated
      neurodegeneration, recent evidence suggests that age-related macular degeneration
      (AMD) may also be exacerbated by retinal iron overload. In the retina, iron is
      necessary for normal cellular function. Iron overload, however, can cause retinal
      toxicity through the generation of oxygen free radicals. Histopathology of eyes
      with macular degeneration has shown elevated levels of iron in the retinal
      pigment epithelium, Bruch membrane, and within drusen, some of which was
      chelatable in vitro with deferoxamine. In this review, the authors summarize the
      evidence that iron overload may contribute to AMD pathogenesis. It is hoped that
      continued investigation of the role of iron and iron associated proteins in the
      retina will uncover clues to AMD pathogenesis and lead to new preventative or
      therapeutic options.

PMID- 18040236
TI  - Intravitreal bevacizumab injections for treatment of central retinal vein
      occlusion: six-month results of a prospective trial.
AB  - PURPOSE: To evaluate the effect of intravitreal bevacizumab (Avastin; Genentech,
      Inc., South San Francisco, CA) injections on visual acuity and foveal retinal
      thickness in patients with central retinal vein occlusion (CRVO). METHODS: In
      this prospective, noncomparative, consecutive, interventional case series, 46
      patients received repeated intravitreal injections (1.25 mg) of bevacizumab. Main
      outcome measures were visual acuity (Snellen and ETDRS charts) and optical
      coherence tomography measurements in a 6-month follow-up period. RESULTS: Mean
      visual acuity improved from 20/250 at baseline to 20/80 at the 6-month follow-up
      (P < 0.001). ETDRS chart findings revealed a mean letter gain +/-SD from baseline
      to 6 months of 13.9 +/- 14.4 letters. Mean central retinal thickness +/-SD
      decreased from 535 +/- 148 microm at baseline to 323 +/- 116 microm at the 6
      month follow-up. Ischemic CRVO was associated with significantly lower visual
      acuity than nonischemic CRVO (P < 0.001). However, visual acuity gain was similar
      in both groups. Independent of duration of symptoms, CRVO was associated with a
      similar gain in visual acuity. CONCLUSION: Intravitreal injection of bevacizumab
      appears to be a new treatment option for patients with macular edema secondary to
      CRVO.

PMID- 18040237
TI  - Intravitreal bevacizumab (avastin) in central retinal vein occlusion.
AB  - PURPOSE: To describe the effects of intravitreal bevacizumab in eyes with macular
      edema resulting from central retinal vein occlusions (CRVO). METHODS:
      Retrospective consecutive case series of patients diagnosed with macular edema
      from CRVO who received intravitreal bevacizumab. RESULTS: Thirty eyes of 29
      patients with an average age of 72 years (range, 54-87 years) had intravitreal
      bevacizumab injections. Mean follow-up was 18.1 weeks. Initial mean visual acuity
      was 20/394. At the 1- and 2-month follow-up, mean visual acuity improved to
      20/237 (n = 26, P = 0.04) and 20/187 (n = 21, P = 0.008), respectively. At the 3-
      and 4-month follow-up, visual acuity improved from 20/228 to 20/157 (n = 15, P =
      0.05) and from 20/313 to 20/213 (n = 11, P = 0.03), respectively. No significant
      changes in visual acuity were found after 4 months though the number of patients
      in this group was small. Duration of treatment effect following an injection
      appears to be limited to 2 months for most patients. No ocular or systemic
      adverse reactions were noted. CONCLUSIONS: The visual benefits of intravitreal
      bevacizumab for macular edema due to CRVO are apparent early but are not
      sustained without repeated injections. Larger clinical studies with long-term
      follow-up will be necessary to better elicit the best regimen for this therapy.

PMID- 18040238
TI  - Effect of oral pentoxifylline on cystoid macular edema associated with central
      retinal vein occlusion.
AB  - PURPOSE: To determine whether oral pentoxifylline, a xanthine-derived
      hemorheologic agent, decreases cystoid macular edema (CME) and improves visual
      acuity in eyes with a perfused central retinal vein occlusion (CRVO). METHODS:
      Retrospective chart review of consecutive patients on pentoxifylline (400 mg po
      TID) for CRVO was performed. Inclusion criteria included CME, pentoxifylline use
      for at least 1 month, and a follow-up period of at least 4 months. Exclusion
      criteria included nonperfused or indeterminate CRVO, the presence of
      neovascularization, and previous or concurrent laser therapy or any other
      treatment for CRVO. Statistical analysis of collected data was performed.
      RESULTS: Eleven patients were identified. All patients had a perfused CRVO. The
      mean best-corrected Early Treatment Diabetic Retinopathy Study visual acuity was
      60 letters (Snellen equivalent 20/128) before the initiation of oral
      pentoxifylline. The mean time from onset of CRVO to start of pentoxifylline
      therapy was 5 months (range, 1-12 months). The mean duration of pentoxifylline
      use was 5.3 months (range, 2.5-10.2 months). The mean follow-up period was 8
      months (range, 2.7-16.5 months). Cystoid macular edema had improved in 64% (7/11)
      of eyes at last follow-up as measured by biomicroscopy and optical coherence
      tomography. The visual acuity was not significantly changed at 62 letters (20/128
      +2) (Student t-test, P = 0.7) at last follow-up. There were no significant side
      effects from pentoxifylline. One patient had mild gastrointestinal disturbance.
      CONCLUSION: Pentoxifylline has a favorable adverse effect profile, and can reduce
      CME in eyes with CRVO. Visual acuity does not appear to change significantly. A
      larger, randomized, multiarmed clinical trial evaluating the effects of
      pentoxifylline as an adjunctive treatment modality may be of benefit since even a
      small positive effect in altering the natural history of CME related to CRVO may
      be of value for these patients.

PMID- 18040239
TI  - Intravitreal triamcinolone acetonide for treatment of serous macular detachment
      in central retinal vein occlusion.
AB  - PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide (IVTA)
      treatment on serous macular detachment in patients with central retinal vein
      occlusion (CRVO). METHODS: Ten eyes of 10 patients with CRVO (6 men and 4 women;
      age range, 54-78 years) made up the study population. The eligibility criteria
      for this study included clinically and angiographically detectable cystoid
      macular edema (CME) in which the presence of serous macular detachment was
      documented by optical coherence tomography (OCT). After IVTA (4 mg/0.1 mL)
      injection, visual and anatomical responses were observed. RESULTS: In all eyes,
      after IVTA injection, CME and serous macular detachment regressed. At 3 months
      and 6 months, CME and serous macular detachment had recurred in 4 (40%) and 5
      eyes (50%), respectively. Patients with recurrence were retreated. No eyes lost
      vision at 1 month, and all eyes had improvement. At 3 months, no eyes had lost
      vision from baseline, and 7 eyes (70%) had improvement. At 6 months, again no
      eyes had lost vision from baseline, and 6 eyes (60%) maintained improved visual
      acuity. CONCLUSIONS: Our study shows that IVTA is effective treatment for serous
      macular detachment in patients with CRVO.

PMID- 18040240
TI  - Role of posterior vitreous detachment induced by intravitreal tissue plasminogen
      activator in macular edema with central retinal vein occlusion.
AB  - PURPOSE: To evaluate the effects of posterior vitreous detachment (PVD) in
      macular edema associated with central retinal vein occlusion (CRVO) treated with
      intravitreal tissue plasminogen activator (tPA). METHODS: The authors conducted a
      retrospective study of 36 eyes of 36 patients with macular edema by CRVO treated
      with intravitreal tPA. In 16 of 21 eyes without pretreatment PVD, PVD developed
      after the treatment. Multiple linear regression analysis was used to evaluate the
      correlation between logarithm of the minimum angle of resolution (logMAR) visual
      acuity (VA) changes and several variables. RESULTS: The VA and macular thickness
      significantly improved after treatment. The pretreatment logMAR VA (R = 0.646; P
      < 0.0001), PVD development after tPA (R = -0.303; P = 0.025), and age (R = 0.255;
      P = 0.050) correlated with the logMAR VA at final visit. The greater improvement
      in logMAR VA was correlated only with PVD development (R = 0.467; P = 0.0041).
      Macular thickness in the eyes with PVD development was significantly less than
      without PVD development at the 6-month visit and the end of follow-up.
      CONCLUSION: The findings suggest that PVD development after intravitreal tPA may
      partly contribute to the resolution of macular edema and a better VA outcome.

PMID- 18040241
TI  - Relationship between retinal vein occlusion and carotid artery lesions.
AB  - PURPOSE: To investigate the relationship between retinal vein occlusion (RVO) and
      carotid artery lesions. METHODS: For patients with RVO who presented to the
      Ophthalmology Department of Tokyo Medical University Hospital between 2000 and
      2003, carotid artery evaluation was possible on 58 eyes of 57 patients aged 51
      years to 88 years (mean, 70.1 years). Thirty-nine patients (40 eyes) had central
      RVO (CRVO), and 18 patients (18 eyes) had branch RVO (BRVO). The observation
      period ranged from 6 months to 28 months (mean, 14 months). A diagnostic
      ultrasound device was used to detect carotid artery lesions. RESULTS: Carotid
      artery lesions were detected in 19 (49%) of 39 patients with CRVO and in 4 (22%)
      of 18 patients with BRVO. In CRVO, 6 eyes without carotid artery lesions but no
      eye with carotid artery lesions had good decimal visual acuity of >or=0.8 (P <
      0.05). Fluorescein angiographic findings identified a significantly (P < 0.01)
      higher incidence of the ischemic type in cases with carotid lesions (15 eyes;
      79%) than in cases without carotid lesions (8 eyes; 40%). CONCLUSIONS: The
      findings suggest that the presence of a carotid artery lesion has a considerable
      association with the development and prognosis of CRVO.

PMID- 18040242
TI  - Changes of intraocular pressure after intravitreal injection of bevacizumab
      (avastin).
AB  - PURPOSE: To determine changes and need to monitor intraocular pressure (IOP)
      following intravitreal injection of bevacizumab (Avastin). METHODS: Seventy
      patients (122 injections) underwent an intravitreal injection of Avastin for
      exudative age-related macular degeneration treatment. Forty-one eyes (59%) had
      single injection, 29 eyes (41%) had repeated injections. IOP was measured before
      and after Avastin injection at 3, 10, and 15 minutes. Twenty-nine eyes were
      evaluated for baseline IOP changes after multiple injections. Statistical
      analysis was performed. RESULTS: Baseline mean IOP was 15.17 +/- 3.42 mm Hg, with
      range from 08 mm Hg to 23 mm Hg. Postinjection 3 minutes the IOP had risen to a
      mean of 36.27 +/- 5.1 mm Hg and fell spontaneously to a mean of 24.56 +/- 5.9 mm
      Hg at 10 minutes. Ten eyes (14%) needed 15 minutes to drop below 30 mm Hg. All
      eyes were below 30 mm Hg at 15 minutes. No significant change between multiple
      baseline IOP measurements was detected. CONCLUSION: Avastin injections caused a
      predictable probably volume-related rise in IOP which never occluded the central
      retinal artery and which spontaneously fell to below 30 mm Hg in all eyes within
      15 minutes. This strong safety profile provides guidelines on monitoring IOP
      after Avastin injections. There was no IOP change after multiple injections.

PMID- 18040243
TI  - Untoward outcomes in 25-gauge versus 20-gauge vitreoretinal surgery.
AB  - PURPOSE: This study compares the incidence of complications in eyes undergoing 25
      gauge versus 20-gauge vitreoretinal procedures. METHODS: Retrospective case
      series. A chart review of consecutive patients who underwent primary 25-gauge
      (129 eyes) and 20-gauge (129 eyes) vitreoretinal surgery by four surgeons at a
      single center between September 2002 and November 2005 was conducted. RESULTS:
      Mean follow-up was 9.1 +/- 4.9 months in 25-gauge eyes and 14.3 +/- 8.4 months in
      20-gauge eyes (P < 0.01). Intraoperative complications were mainly rhegmatogenous
      in nature and occurred at statistically similar incidence (4.7% in 25-gauge eyes,
      6.9% in 20-gauge eyes). Postoperative complications that were significantly
      associated with surgical method included hypotony and serous choroidal effusions
      (7.9% in 25-gauge eyes, 1.6% in 20-gauge eyes, P = 0.02). Other postoperative
      complications noted included retinal tears and detachments (5.4% in 25-gauge
      eyes, 4.7% in 20-gauge eyes), persistent vitreous hemorrhage (5.4% in each
      group), and new vitreous hemorrhage (3.9% in 25-gauge eyes, 0.8% in 20-gauge
      eyes). Endophthalmitis was noted only in 25-gauge eyes in 2 cases (1.6%).
      Cataract progression occurred at similar rates in both groups (46%). CONCLUSION:
      25-gauge surgery is associated with a significantly greater incidence of
      postoperative serous choroidal effusions and hypotony. Of particular concern in
      25-gauge surgery is the increased risk of associated endophthalmitis. Operative
      indications and case selection may be important in minimizing the tendency toward
      certain postoperative events.

PMID- 18040244
TI  - Silicone oil tamponade in 23-gauge transconjunctival sutureless vitrectomy.
AB  - PURPOSE: To describe 20 consecutive patients treated with 23-gauge
      transconjunctival sutureless vitrectomy and silicone oil tamponade for retinal
      detachments (RD) of different etiologies. METHODS: Prospective case series.
      Twenty patients with complex retinal detachment were submitted to a primary 23
      gauge transconjunctival pars plana vitrectomy: rhegmatogenous retinal detachment
      with proliferative vitreoretinopathy (RRD + PVR) in 7 cases, diabetic tractional
      retinal detachment (DTRD) in 5 cases, giant retinal tear (GRT) in 2 cases, RRD
      with multiple tears in 2 cases, GRT + uveitis in 1 case, RRD + uveitis in 1 case,
      DTRD + RRD in 1 case, and RRD + PVR with intraocular foreign body (IOFB) in 1
      case. Length of postoperative follow up ranged from 3 to 14 months. RESULTS:
      Final visual acuity ranged from 20/25 to hand motion. Postoperatively, none of
      the 20 eyes had hypotony or leakage of silicone oil through the sclerotomies.
      Seventeen out of 20 (85%) had improved vision. CONCLUSION: Silicone oil tamponade
      was demonstrated to be a feasible option in conjunction with 23-g
      transconjunctival sutureless vitrectomy to treat complex retinal detachment.

PMID- 18040245
TI  - Removal of silicone oil with 25-gauge transconjunctival sutureless vitrectomy
      system.
AB  - PURPOSE: To report a new and simple technique for silicone oil removal from pars
      plana with 25-gauge (G) transconjunctival sutureless vitrectomy system (TSVS).
      METHODS: In this prospective, interventional clinical trial, 13 eyes underwent
      silicone oil (1000 centistokes) removal from pars plana passively, with 25-G
      TSVS, between January and May 2005. Main outcome measures were postoperative
      visual acuity, intraocular pressure (IOP), silicone oil removal time,
      complications, and number of sutured sites. RESULTS: In all eyes silicone oil was
      removed successfully under sub-Tenon (n = 12) and topical (n = 1) anesthesia. The
      mean silicone oil removal time was 7.27 +/- 0.48 minutes. No intraoperative
      complications were reported. No suture placement was necessary. Mean
      postoperative follow-up period was 3.92 +/- 1.49 (range: 3-7) months. Visual
      acuity improved or stabilized in 11 (84.61%) eyes. Retinal redetachment occurred
      in 2 (15.38%) eyes resulting in a decrease in vision. Decrease in postoperative
      IOP was found only at 2 hours (P = 0.003). Postoperatively, transient hypotony at
      2 hours (n = 1) and transient vitreous hemorrhage (n = 1) were noted. There were
      no cases of choroidal detachment, endophthalmitis, clinically significant corneal
      endothelial decompensation, or macular edema. CONCLUSION: Removal of silicone oil
      of 1000 centistokes with 25-G transconjunctival sutureless sclerotomies was
      effective and safe.

PMID- 18040246
TI  - Current visual and anatomic outcomes of pneumatic retinopexy.
AB  - PURPOSE: To assess current visual and anatomic outcomes of pneumatic retinopexy
      (PR) for the repair of rhegmatogenous retinal detachment (RD). METHODS:
      Retrospective chart review of 150 patients who underwent PR for RD between
      January 2000 and February 2005. Patients with a history of scleral buckling,
      Lincoff balloon, or proliferative diabetic retinopathy in the same eye were
      excluded. RESULTS: Successful reattachment was achieved in 76.7% with a single
      procedure and 98.7% after additional procedures. A total of 17.3% underwent a
      subsequent procedure for a new or persistent tear. The success rate remained
      consistent in pseudophakic and aphakic eyes, and eyes with traumatic detachments,
      macular detachment, multiple breaks, poor preoperative visual acuity (VA)
      (<20/50), superior and inferior lattice degeneration, >or=6 clock hours of
      detachment, and prior pars plana vitrectomy. A total of 2.7% of eyes underwent a
      second additional procedure for RD. A total of 32% of males versus 15.3% of
      females underwent an additional procedure for RD (P = 0.07). Final VA >or=20/50
      was achieved in 80.8% of macula-on and 73.6% of macula-off RDs. Of eyes that
      underwent an additional procedure, final VA >or=20/50 was achieved in 63.2% of
      macula-on and 43.8% of macula-off RDs, and those with macula-on RD lost a mean of
      1.79 (+/-4.9) lines of Snellen VA, while those with macula-off RD gained a mean
      of 5.6 (+/-4.6) lines (P = 0.00006). CONCLUSIONS: : PR had a high anatomic
      success rate in eyes with a wide variety of complicated RDs. Male sex may be a
      risk factor for failed PR. Careful monitoring and treatment of postoperative
      tears is important in preventing redetachment.

PMID- 18040247
TI  - Rituximab penetrates full-thickness retina in contrast to tissue plasminogen
      activator control.
AB  - PURPOSE: To assess whether intravitreal rituximab 1 mg/0.1 cc penetrates the
      retina of Dutch-belted rabbits. METHODS: Two right eyes of two rabbits were
      injected with intravitreal rituximab 1 mg/0.1 mL, and one right eye of one rabbit
      was injected with intravitreal tissue plasminogen activator (tPA) 12.5 microg/0.1
      mL, as a protein control. The three left eyes received no intravitreal
      injections. The rabbits were killed; the eyes were enucleated and immediately
      frozen at -80 degrees C. Rituximab was detected using rabbit antihuman IgG (whole
      molecule) peroxidase conjugated antibody. tPA was detected using an antihuman IgG
      with a sheep antihuman tPA antibody conjugated with peroxidase. RESULTS: There
      was staining in all retinal layers of the two eyes injected with intravitreal
      rituximab, and no staining of the retina in the eye injected with intravitreal
      tPA. The three control eyes showed no staining in any retinal layer. CONCLUSION:
      Intravitreal rituximab at a dose of 1 mg/0.1 cc penetrates the retina of Dutch
      belted rabbits while the control intravitreal tPA at a dose of 12.5 microg/0.1 cc
      does not.

PMID- 18040248
TI  - Plasmin-assisted vitrectomy for management of proliferative membrane in
      proliferative diabetic retinopathy: a pilot study.
AB  - PURPOSE: To demonstrate the feasibility of autologous plasmin for treatment of
      proliferative diabetic retinopathy. METHODS: The study examined prospectively six
      patients with bilateral proliferative diabetic retinopathy. Comparisons of the
      surgical time and the incidence of retinal tears were made between the eyes
      treated with autologous plasmin and their respective opposite eyes, which were
      treated without plasmin. RESULTS: All eyes treated with autologous plasmin
      required significantly less surgical time (68 versus 89 minutes, P = 0.04, paired
      t-test). In the plasmin group, no additional surgical procedures for removing the
      proliferative membrane were needed, including membrane delamination or
      segmentation. Moreover, with plasmin pretreatment, there were no retinal tears,
      which was in contrast to the control group, where three eyes with retinal tears
      were observed. There was no significant difference found between the two groups
      for final visual outcomes. CONCLUSION: Autologous plasmin may be beneficial in
      the surgical management of proliferative diabetic retinopathy.

PMID- 18040249
TI  - Plasmin enzyme-assisted vitreoretinal surgery in congenital X-linked
      retinoschisis: surgical techniques based on a new classification system.
AB  - PURPOSE: To review the surgical outcome of autologous plasmin enzyme-assisted
      vitreoretinal surgery in managing complications associated with congenital X
      linked retinoschisis (CXLRS). METHODS: Medical records of 20 patients (22 eyes)
      with CXLRS complications, treated with autologous plasmin enzyme-assisted
      vitreoretinal surgery, were reviewed. Surgical techniques were adapted according
      to a new CXLRS classification. RESULTS: Median age of the cohort was 3.5 years.
      Indications for surgical intervention included 8 eyes with schisis involving or
      threatening the macula, 7 eyes with rhegmatogenous retinal detachment, 4 eyes
      with tractional retinal detachment, 1 eye with vitreous and intraschisis
      hemorrhage, 1 eye with obstruction of the macula by an overhanging bullous
      schisis cavity, and 1 eye with macular pucker. Ninety-one percent (20/22) of eyes
      had retinal attachment postoperatively after an average of 1.3 procedures per
      eye. Of the eyes in which visual acuity was measured, 53% (8/15) improved, 33%
      (5/15) had no change, and 13% (2/15) lost vision. CONCLUSION: Plasmin enzyme
      assisted vitreoretinal surgery is a safe and effective method for managing the
      complications associated with CXLRS. Most patients had improved or stable
      postoperative visions.

PMID- 18040250
TI  - Elevated levels of cystatin C and tenascin-C in schisis cavities of patients with
      congenital X-linked retinoschisis.
AB  - PURPOSE: To describe the finding of tenascin C and cystatin-C in the intraschisis
      cavities of pediatric patients with intraretinal schisis cavities. METHODS: Three
      patients with congenital X-linked retinoschisis (CXLRS) and one girl with
      clinical retinoschisis underwent vitrectomy for vision-threatening schisis
      cavities. At the time of surgery undiluted samples of intraschisis fluid and
      vitreous fluid from four eyes (three male and one female) were obtained and
      analyzed by gel electrophoresis and protein sequencing for the presence of
      tenascin C and cystatin-C. RESULTS: Tenascin C and cystatin-C were found in all
      four samples of fluid from the intraschisis cavities, including a girl with a
      clinical presentation of CXLRS. The vitreous samples did not have detectable
      levels of either protein as determined by gel electrophoresis. CONCLUSIONS:
      Tenascin C and cystatin-C levels are elevated in intraschisis cavity fluid.
      Interestingly, this was also found in a girl not carrying a mutation in the
      retinoschisin gene, indicating that elevated concentrations of tenascin C and
      cystatin-C result from pathologic changes in the retina and not from the presence
      of aberrant retinoschisin.

PMID- 18040251
TI  - Microplasmin-induced posterior vitreous detachment affects vitreous oxygen
      levels.
AB  - PURPOSE: To determine if enzymatic induction of a posterior vitreous detachment
      (PVD) and/or vitreous liquefaction affects O2 concentration in the vitreous
      cavity in animals with vascularized and avascular retinal circulations. METHODS:
      Either microplasmin or hyaluronidase was injected intravitreally into guinea pigs
      (avascular retinal circulation), brown Norway rats (vascularized retinal
      circulation without fovea), or cats (vascularized retinal circulation with fovea)
      with the contralateral eye used as a control. One to 2 weeks post injection,
      vitreal oxygen concentration was measured using a highly sensitive, platinum
      based fluorophore O2 sensor. In addition, control and microplasmin-injected rats,
      guinea pigs, and cats were exposed to 100% oxygen and vitreal O2 levels were
      measured over time. Scanning electron microscopy (SEM) was used to evaluate the
      vitreoretinal interface for the presence of a PVD. RESULTS: In animals with a
      vascularized retinal circulation (brown Norway rats and cats), intravitreal
      injection of microplasmin with induction of a PVD significantly increased
      baseline O2 concentration in the vitreous cavity compared to hyaluronidase
      injected eyes and controls in rats (35, 25, and 23 mm Hg, P < 0.001 and P <
      0.001, respectively) and cats (26, 18, and 16 mm Hg, P < 0.01 and P < 0.001,
      respectively). Interestingly, intravitreal injection of hyaluronidase (vitreous
      liquefaction without induction of a PVD) did not significantly increase vitreal
      O2 levels in any of the animal species (P > 0.1). Upon exposure to 100% oxygen by
      facemask, microplasmin injected animals showed a rapid increase in vitreal oxygen
      levels compared to hyaluronidase injected animals and controls, indicating that
      the presence of a PVD allows rapid O2 exchange within the vitreous cavity.
      Similarly, once O2 was discontinued, the O2 concentration decreased in a
      similarly rapid rate. SEM showed smooth retinal surfaces in microplasmin-injected
      cat eyes, indicating the presence of a PVD which was not present in hyaluronidase
      injected or control eyes. CONCLUSION: The results suggest that enzymatic-assisted
      PVD with microplasmin increases vitreal O2 levels and increases the rate of O2
      exchange within the vitreous cavity.

PMID- 18040252
TI  - Autofluorescence of congenital hypertrophy of the retinal pigment epithelium.
AB  - PURPOSE: To describe the autofluorescence features of CHRPE. DESIGN:
      Noncomparative case series. PARTICIPANTS: Thirteen consecutive eyes with CHRPE.
      METHODS: : CHRPE was studied with fundus photography and autofluorescence.
      Autofluorescence was judged relative to the surrounding retinal pigment
      epithelium. MAIN OUTCOME MEASURE: Autofluorescence features of CHRPE. RESULTS:
      The mean CHRPE basal dimension was 4.75 mm and the tumor location was between the
      macular and equator (n = 10) or equator and ora serrata (n = 3). Overall, CHRPE
      show hypoautofluorescence in every case and was classified as trace (n = 1),
      moderate (n = 6), or marked (n = 6) hypoautofluorescence. Compared to the central
      portion of CHRPE, the margin showed isoautofluorescence (n = 8) or trace
      hyperautofluorescence (n = 5). There were eight lesions with lacunae and this
      feature generally showed trace to moderate hyperautofluorescence (n = 6). A
      nonpigmented halo was present surrounding six lesions, generally showing trace
      hyperautofluorescence (n = 3). A pigmented halo was present surrounding eight
      lesions, usually showing isoautofluorescence (n = 6). CONCLUSIONS: CHRPE shows
      striking hypoautofluorescence and this correlates with known histopathologic
      evidence of lack of lipofuscin in the retinal pigment epithelium of CHRPE. The
      lacunae showed general mild hyperautofluorescence that might correlate with
      scleral autofluorescence.

PMID- 18040253
TI  - Autofluorescence of basal laminar drusen.
AB  - PURPOSE: To compare noninvasive autofluorescence (AF) photography with
      conventional fundus photography and fluorescein angiography (FA) in the detection
      of basal laminar drusen (BLD). METHODS: A retrospective case review of 20
      patients with BLD studied with AF and conventional imaging was performed. Three
      selected patients with different degrees of BLD are presented. AF imaging
      employed an excitation filter at 580 nm and a barrier filter at 695 nm with
      acquisition by a Topcon 50X fundus camera. Corresponding detail regions in each
      image were enlarged for comparison. The AF detail image was registered by a
      projective transformation in Matlab (Mathworks 7.0, Natick, MA) with the color
      photograph/red free photograph (RF) and/or FA image detail for exact
      superimposition in Photoshop and lesion comparison. RESULTS: Each visible drusen
      in the color or RF photograph corresponded when superimposed to a focal
      hypoautofluorescent lesion in the AF image. However, similar to the starry sky
      pattern in FA, the AF lesions significantly outnumbered the clinically evident
      drusen. When BLD lesions were not advanced enough to show the classic starry sky
      fluorescein hyperfluorescence, the BLD were detectable with AF. CONCLUSIONS: In
      our case series, AF imaging demonstrated a higher level of sensitivity when
      compared with conventional fundus photography and is less invasive than FA for
      the detection of BLD. Fundus AF, therefore, is valuable for diagnosing and
      following BLD, particularly since these patients are at risk for development of
      pseudovitelliform detachment which may simulate CNV.

PMID- 18040254
TI  - Autofluorescence of orange pigment overlying small choroidal melanoma.
AB  - PURPOSE: To describe the autofluorescence features of orange pigment
      (intracellular lipofuscin) overlying small presumed choroidal melanomas. METHODS:
      The diagnostic testing results (fluorescein angiography, optical coherence
      tomography, and fundus autofluorescence imaging) for two patients with pigmented
      choroidal melanoma and two patients with nonpigmented choroidal melanoma were
      reviewed. RESULTS: Clinically, the intracellular lipofuscin pigment appeared
      brown overlying the nonpigmented melanoma (two cases) and orange overlying the
      pigmented melanoma (two cases). Fluorescein angiography demonstrated that the
      lipofuscin pigment displayed fluorescein blockage in all four cases. Optical
      coherence tomography revealed serous retinal detachment in all four cases. Fundus
      autofluorescence imaging showed discrete, bright hyperautofluorescence of the
      orange pigment separated by hypoautofluorescent voids. The melanoma was
      isoautofluorescent. CONCLUSIONS: Intracellular lipofuscin overlying small
      choroidal melanomas shows discrete and bright hyperautofluorescence. The
      brightness correlates directly with the clinically visible orange pigment.

PMID- 18040255
TI  - Rebound of cystoid macular edema with continued use of acetazolamide in patients
      with retinitis pigmentosa.
AB  - PURPOSE: To demonstrate the presence of a rebound effect with the use of
      acetazolamide for the treatment of cystoid macular edema (CME) in patients with
      retinitis pigmentosa (RP). METHODS: Six patients with RP and cystic-appearing
      lesions in the macula demonstrated by fluorescein angiography and/or optical
      coherence tomography (OCT) were treated with an oral form of carbonic anhydrase
      inhibitor (acetazolamide [500 mg]) as a single daily dose. RESULTS: All patients,
      treated with acetazolamide for a period of 3 weeks to 5 weeks, had initial
      improvement of macular edema demonstrated by OCT. However, extended use of
      acetazolamide, for at least 8 weeks to 12 weeks, resulted in recurrence (rebound)
      of CME in 3 of the 6 patients. CONCLUSIONS: Results from our study suggest that
      rebound of CME with the continued use of acetazolamide observed by OCT may occur
      more frequently than previously appreciated.

PMID- 18040256
TI  - Sensitivity and specificity of the optos optomap for detecting peripheral retinal
      lesions.
AB  - PURPOSE: To compare the sensitivity and specificity of the Optomap Panoramic200
      wide-field confocal scanning laser imaging system for detecting peripheral
      retinal lesions. METHODS: Optomap images were obtained in patients with known
      retinal pathology. Two masked retinal specialists evaluated Optomap images to
      identify lesions requiring referral to a retinal specialist. Their performance
      was compared to gold standard examination with scleral indentation performed by a
      retinal specialist. Sensitivity was calculated overall and again for lesions that
      were found on clinical examination to require treatment. These sensitivities were
      calculated separately for lesions posterior and anterior to the equator.
      Specificity was calculated from fellow eyes that were found to have no pathology
      on clinical examination. RESULTS: For retinal lesions posterior to the equator,
      sensitivity was 74% (95% confidence interval [95% CI] 61%-87%) overall for all
      lesions and 76% (95% CI 59%-93%) for lesions requiring treatment. For anterior
      lesions, sensitivity was 45% (95% CI 28%-62%) overall and 36% (95% CI 14%-58%)
      for treatable lesions. Specificity was 85% (95% CI 63%-100%). CONCLUSIONS: The
      Optomap showed high specificity and moderate sensitivity for lesions posterior to
      the equator and low sensitivity for lesions anterior to the equator.

PMID- 18040257
TI  - Effect of blood on susceptibility to Staphylococcal endophthalmitis.
AB  - PURPOSE: The authors examined the effect of blood on susceptibility to
      experimental endophthalmitis. METHODS: Forty rabbits received an injection of 5
      25 colony-forming units of Staphylococcus epidermidis into the vitreous of the
      right eye. Twenty of these same eyes received a subsequent intravitreal injection
      of 0.2 mL blood while the remaining 20 received an intravitreal injection of 0.2
      mL of a salt solution. All eyes were examined daily for signs of endophthalmitis.
      Vitreous cultures were obtained on day 2 from 30 of the 40 rabbits. Twenty
      rabbits were assigned for culture and euthanasia at day 5 and those remaining
      were cultured and killed at day 7. RESULTS: In rabbits with blood and bacteria,
      10 of 15 (67%) were culture positive at 2 days, compared to 2 of 15 (13%) that
      received salt solution and bacteria (P < 0.01). At days 5 and 7 there was no
      statistically significant difference in culture results. However, inflammatory
      scores were significantly higher at days 3-7 in rabbits with blood compared to
      those with salt solution (P <or= 0.02). CONCLUSIONS: : In this model, eyes with
      intravitreal blood were more likely to develop culture-positive endophthalmitis.
      Cultures were more likely to be positive at day 2, whereas inflammatory signs
      were more prevalent at days 5 and 7.

PMID- 18040258
TI  - 27-gauge transconjunctival nonvitrectomizing vitreous surgery for epiretinal
      membrane removal.

PMID- 18040259
TI  - Active removal of silicone oil with 25-gauge sutureless system.

PMID- 18040260
TI  - Twenty-gauge transconjunctival sutureless vitrectomy trocar system.

PMID- 18040261
TI  - Diagnostic and therapeutic challenges.

PMID- 18040262
TI  - Mycobacterium haemophilum: a rare cause of endophthalmitis.
AB  - Nontuberculous mycobacterial (NTM) infections are becoming an increasingly
      important complication in ophthalmology, particularly among immunocompromised
      patients. We report a case of NTM in a 66-year-old male immunosuppressed after
      cardiac transplantation. Chronic granulomatous iridocyclitis progressed to
      purulent endophthalmitis despite intraocular and systemic antimicrobial therapy.
      Direct immunoflourescent staining of the vitrectomy specimen revealed acid-fast
      bacilli. Biopsies of nodular skin lesions revealed non-caseating granulomas with
      acid-fast bacilli. Cultures of skin and eye biopsies yielded Mycobacterium
      haemophilum. Despite aggressive combination antimicrobial therapy, the eye was
      eventually enucleated. Resolution of systemic infection occurred with the
      addition of granulocyte macrophage-colony stimulating factor. This is the first
      reported case of M. haemophilum endophthalmitis.

PMID- 18040263
TI  - Detection of a microrip using spectral-domain optical coherence tomography with
      three-dimensional image reconstruction.

PMID- 18040264
TI  - Re: development of ranibizumab, an anti-vascular endothelial growth factor
      antigen binding fragment, as therapy for neovascular age-related macular
      degeneration.

PMID- 18040266
TI  - Re: Susac syndrome in four male patients.

PMID- 18040268
TI  - Normal human primary CD4+ T lymphocytes synthesize and release functional
      osteoprotegerin in vitro.
AB  - Osteoprotegerin (OPG) acts as a decoy receptor for receptor activator of nuclear
      factor-kappaB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL).
      OPG regulates bone remodeling and the immune response. The primary objective was
      to decipher, among human peripheral blood mononuclear leukocytes (PBML) that
      produce OPG, the subset(s) responsible for this synthesis and its regulation. To
      this end, normal human PBML and CD4-, 8-, 19-, 14-enriched subpopulations were
      studied in vitro for OPG synthesis. PBML were subjected to adherence and
      immunomagnetic separation, and OPG expression was analyzed by PCR, northern and
      western blotting, and ELISA. The antiapoptotic effects of OPG were studied on
      TRAIL-stimulated RPMI 8226 myeloma cells. OPG was time-dependently produced by
      primary CD4+ T lymphocytes exclusively. OPG secretion was upregulated by anti-CD3
      antibody stimulation or incubation with interleukin (IL)-4, IL-1beta, TNF-alpha,
      GM-CSF, and vitamin D(3). In contrast, IL-10 inhibited the basal and IL-4-induced
      production of OPG by T cells. Conditioned media from activated T lymphocytes
      decreased TRAIL-induced apoptosis of RPMI 8226 cells. This effect was reversed by
      addition of RANKL to the T-cell conditioned media. As human immunodeficiency
      virus-1 (HIV-1) targets CD4+ T cells, we evaluated the effects of recombinant HIV
      1 gp120 proteins on OPG synthesis. The gp120 from three different HIV-1 strains
      significantly reduced the basal output of OPG from T cells. Furthermore, all four
      protease inhibitors (PIs) used in highly active antiretroviral therapy decreased
      OPG synthesis by human blood T cells, nelfinavir being the most efficient PI. The
      simultaneous presence of an HIV-1 gp120 and a PI abrogated the basal output of
      OPG. In conclusion, these results highlight a new role for T lymphocytes involved
      in pathologies. Activated CD4+ T cells could, through OPG release, have a
      paracrine effect on adjacent cells and contribute to reduce the local process of
      bone remodeling and cellular apoptosis.

PMID- 18040269
TI  - 'One medicine---one pathology': are veterinary and human pathology prepared?
AB  - The American Medical Association and the American Veterinary Medical Association
      have recently approved resolutions supporting 'One Medicine' or 'One Health' that
      bridge the two professions. The concept is far from novel. Rudolf Virchow, the
      Father of Modern Pathology, and Sir William Osler, the Father of Modern Medicine,
      were outspoken advocates of the concept. The concept in its modern iteration was
      re-articulated in the 1984 edition of Calvin Schwabe's 'Veterinary Medicine and
      Human Health.' The veterinary and medical pathology professions are steeped in a
      rich history of 'One Medicine,' but they have paradoxically parted ways, leaving
      the discipline of pathology poorly positioned to contribute to contemporary
      science. The time has come for not only scientists but also all pathologists to
      recognize the value in comparative pathology, the consequences of ignoring the
      opportunity and, most importantly, the necessity of preparing future generations
      to meet the challenge inherent in the renewed momentum for 'One Medicine.' The
      impending glut of new genetically engineered mice creates an urgent need for
      prepared investigators and pathologists.

PMID- 18040270
TI  - Endothelial NOS is required for SDF-1alpha/CXCR4-mediated peripheral endothelial
      adhesion of c-kit+ bone marrow stem cells.
AB  - In the era of intravascular approaches for regenerative cell therapy, the
      underlying mechanisms of stem cell migration to non-marrow tissue have not been
      clarified. We hypothesized that next to a local inflammatory response implying
      adhesion molecule expression, endothelial nitric oxide synthase (eNOS)-dependent
      signaling is required for stromal- cell-derived factor-1 alpha (SDF-1alpha)
      induced adhesion of c-kit+ cells to the vascular endothelium. SDF-1alpha/tumor
      necrosis factor-alpha (TNF-alpha)-induced c-kit+-cell shape change and migration
      capacity was studied in vitro using immunohistochemistry and Boyden chamber
      assays. In vivo interaction of c-kit+ cells from bone marrow with the endothelium
      in response to SDF-1alpha/TNF-alpha stimulation was visualized in the cremaster
      muscle microcirculation of wild-type (WT) and eNOS (-/-) mice using intravital
      fluorescence microscopy. In addition, NOS activity was inhibited with N-nitro-L
      arginine-methylester-hydrochloride in WT mice. To reveal c-kit+-specific adhesion
      behavior, endogenous leukocytes (EL) and c-kit+ cells from peripheral blood
      served as control. Moreover, intercellular adhesion molecule-1 (ICAM-1) and CXCR4
      were blocked systemically to determine their role in inflammation-related c-kit+
      cell adhesion. In vitro, SDF-1alpha enhanced c-kit+-cell migration. In vivo, SDF
      1alpha alone triggered endothelial rolling-not firm adherence-of c-kit+ cells in
      WT mice. While TNF-alpha alone had little effect on adhesion of c-kit+ cells, it
      induced maximum endothelial EL adherence. However, after combined treatment with
      SDF-1alpha+TNF-alpha, endothelial adhesion of c-kit+ cells increased independent
      of their origin, while EL adhesion was not further incremented. Systemic
      treatment with anti-ICAM-1 and anti-CXCR4-monoclonal antibody completely
      abolished endothelial c-kit+-cell adhesion. In N-nitro-L-arginine-methylester
      hydrochloride-treated WT mice as well as in eNOS (-/-) mice, firm endothelial
      adhesion of c-kit+ cells was entirely abrogated, while EL adhesion was
      significantly increased. The chemokine SDF-1alpha mediates firm adhesion c-kit+
      cells only in the presence of TNF-alpha stimulation via an ICAM-1- and CXCR4
      dependent mechanism. The presence of eNOS appears to be a crucial and specific
      factor for firm c-kit+-cell adhesion to the vascular endothelium.

PMID- 18040271
TI  - Finding a match: how do homologous sequences get together for recombination?
AB  - Decades of research into homologous recombination have unravelled many of the
      details concerning the transfer of information between two homologous sequences.
      By contrast, the processes by which the interacting molecules initially
      colocalize are largely unknown. How can two homologous needles find each other in
      the genomic haystack? Is homologous pairing the result of a damage-induced
      homology search, or is it an enduring and general feature of the genomic
      architecture that facilitates homologous recombination whenever and wherever
      damage occurs? This Review presents the homologous-pairing enigma, delineates our
      current understanding of the process and offers guidelines for future research.

PMID- 18040272
TI  - Association of progression-free survival with patient-reported outcomes and
      survival: results from a randomised phase 3 trial of panitumumab.
AB  - In a randomised phase 3 trial, panitumumab significantly improved progression
      free survival (PFS) in patients with refractory metastatic colorectal cancer
      (mCRC). This analysis characterises the association of PFS with CRC symptoms,
      health-related quality of life (HRQoL), and overall survival (OS). CRC symptoms
      (NCCN/FACT CRC symptom index, FCSI) and HRQoL (EQ-5D) were assessed for 207
      panitumumab patients and 184 best supportive care (BSC) patients who had at least
      one post-baseline patient-reported outcome (PRO) assessment. Patients alive at
      week 8 were included in the PRO and OS analyses and categorised by their week 8
      progression status as follows: no progressive disease (no PD; best response of at
      least stable disease) vs progressive disease (PD). Standard imputation methods
      were used to assign missing values. Significantly more patients were progression
      free at weeks 8-24 with panitumumab vs BSC. After excluding responders, a
      significant difference in PFS remained favouring panitumumab (HR=0.63, 95%
      CI=0.52-0.77; P<0.0001). At week 8, lack of disease progression was associated
      with significantly and clinically meaningful lower CRC symptomatology for both
      treatment groups and higher HRQoL for panitumumab patients only. Overall survival
      favoured no PD patients vs PD patients alive at week 8. Lack of disease
      progression was associated with better symptom control, HRQoL, and OS.

PMID- 18040273
TI  - A clinical phase II study with sorafenib in patients with progressive hormone
      refractory prostate cancer: a study of the CESAR Central European Society for
      Anticancer Drug Research-EWIV.
AB  - Sorafenib is a multi-kinase inhibitor with antiangiogenic and antiproliferative
      activity. The activity of sorafenib in progressive hormone-refractory prostate
      cancer (HRPC) patients was investigated in a phase II clinical study. Progressive
      HRPC patients received sorafenib 400 mg bid p.o. continuously. Only patients with
      no prior chemotherapy, and either one-unidimensional measurable lesion according
      to RECIST-criteria or increasing prostate-specific antigen (PSA) values
      reflecting a hormone-refractory situation, were eligible for study entry. The
      primary study objective was the rate of progression-free survival of >/=12 weeks
      (PFS12). Secondary end points were overall response, overall survival, and
      toxicity. Fifty-seven patients with PC were enrolled. Two patients had to be
      withdrawn from the set of eligible patients. According to RECIST criteria, 4
      patients out of 55 evaluable patients showed stable disease (SD). According to
      PSA-response, we saw 11 patients with SD PSA and 2 patients were responders at 12
      weeks (PFS12=17/55=31%). Among the 257 adverse events, 15 were considered drug
      related of maximum CTC-grade 3. Twenty-four serious adverse events occurred in 14
      patients (14/55=26%). Seven of them were determined to be drug related. No
      treatment-related death was observed. Sorafenib has antitumour activity in HRPCP
      when evaluated for RECIST- and PSA-based response. Further investigation as a
      component of combination regimens is necessary to evaluate its definite or
      overall clinical benefit for HRPCP.

PMID- 18040274
TI  - Evaluation of 18F-2-deoxy-2-fluoro-glucose positron emission tomography for
      gastric cancer screening in asymptomatic individuals undergoing endoscopy.
AB  - (18)F-2-deoxy-2-fluoro-glucose Positron Emission Tomography (FDG-PET) has been
      recently proposed as a promising cancer-screening test. However, the validity of
      FDG-PET in cancer screening has not been evaluated. We investigated the
      sensitivity of FDG-PET compared with upper gastric endoscopy in gastric cancer
      screening for asymptomatic individuals. A total of 2861 consecutive subjects
      (1600 men and 1261 women) who were asymptomatic and who underwent both FDG-PET
      and upper gastrointestinal endoscopy between 1 February 2004 and 31 January 2005
      were included in this study. Both endoscopists and a radiologist were unaware of
      the results of the other diagnostic tests. The FDG-PET images were examined using
      criteria determined by the pattern of FDG accumulation. Sensitivity and
      specificity of FDG-PET were calculated compared with endoscopic diagnosis as the
      gold standard. Among 2861 subjects enrolled in the study, there were 20 subjects
      with gastric cancer, of whom 18 were T1 in depth of cancer invasion. Positive FDG
      PET results were obtained only in 2 of the 20 cancer subjects. The calculated
      sensitivity and specificity for overall gastric cancers were 10.0% (95%
      confidence interval (CI): 1.2-31.7%) and 99.2% (95% CI: 98.8-99.5%),
      respectively. (18)F-2-deoxy-2-fluoro-glucose Positron Emission Tomography was
      poorly sensitive for detection of gastric cancer in the early stages.

PMID- 18040277
TI  - TGF-beta1 and TGF-beta2 expression after traumatic human spinal cord injury.
AB  - STUDY DESIGN: Immunohistochemical investigation in control and lesioned human
      spinal cords. OBJECTIVES: To assess the spatial and temporal expression patterns
      of transforming growth factor-beta1 and -beta2 (TGF-beta1 and TGF-beta2) in the
      human spinal cord after traumatic injury. SETTING: Germany, Aachen, Aachen
      University Hospital. METHODS: Sections from human spinal cords from 4 control
      patients and from 14 patients who died at different time points after traumatic
      spinal cord injury (SCI) were investigated immunohistochemically. RESULTS: In
      control cases, TGF-beta1 was confined to occasional blood vessels, intravascular
      monocytes and some motoneurons, whereas TGF-beta2 was only found in intravascular
      monocytes. After traumatic SCI, TGF-beta1 immunoreactivity was dramatically
      upregulated by 2 days after injury (the earliest survival time investigated) and
      was detected within neurons, astrocytes and invading macrophages. The staining
      was most intense over the first weeks after injury but gradually declined by 1
      year. TGF-beta2 immunoreactivity was first detected 24 days after injury. It was
      located in macrophages and astrocytes and remained elevated for up to 1 year. In
      white matter tracts undergoing Wallerian degeneration, there was no induction of
      either isoform. CONCLUSION: The early induction of TGF-beta1 at the point of SCI
      suggests a role in the acute inflammatory response and formation of the glial
      scar, while the later induction of TGF-beta2 may indicate a role in the
      maintenance of the scar. Neither of these TGF-beta isoforms appears to contribute
      to the astrocytic scar formation in nerve fibre tracts undergoing Wallerian
      degeneration.

PMID- 18040278
TI  - International lower urinary tract function basic spinal cord injury data set.
AB  - OBJECTIVE: To create the International Lower Urinary Tract Function Basic Spinal
      Cord Injury (SCI) Data Set within the framework of the International SCI Data
      Sets. SETTING: International working group. METHODS: The draft of the Data Set
      was developed by a working group consisting of the members appointed by the
      International Continence Society, the European Association of Urology, the
      American Spinal Injury Association (ASIA), the International Spinal Cord Society
      (ISCoS) and a representative of the Executive Committee of the International SCI
      Standards and Data Sets. The final version of the Data Set was developed after
      review and comments by the members of the Executive Committee of the
      International SCI Standards and Data Sets, the ISCoS Scientific Committee, ASIA
      Board, relevant and interested (international) organizations and societies
      (around 40) and persons, and the ISCoS Council. Endorsement of the Data Set by
      relevant organizations and societies will be obtained. To make the Data Set
      uniform, each variable and each response category within each variable have been
      specifically defined in a way that is designed to promote the collection and
      reporting of comparable minimal data. RESULTS: Variables included in the
      International Lower Urinary Tract Function Basic SCI Data Set are as follows:
      date of data collection, urinary tract impairment unrelated to spinal cord
      lesion, awareness of the need to empty the bladder, bladder emptying, average
      number of voluntary bladder emptyings per day during the last week, incontinence
      within the last 3 months, collecting appliances for urinary incontinence, any
      drugs for the urinary tract within the last year, surgical procedures on the
      urinary tract and any change in urinary symptoms within the last year. Complete
      instruction for data collection, data sheet and training cases available at the
      website of ISCoS (www.iscos.org.uk) and ASIA (www.asia-spinalinjury.org).

PMID- 18040280
TI  - Many human immunoglobulin heavy-chain IGHV gene polymorphisms have been reported
      in error.
AB  - The identification of the genes that make up rearranged immunoglobulin genes is
      critical to many studies. For example, the enumeration of mutations in
      immunoglobulin genes is important for the prognosis of chronic lymphocytic
      leukemia, and this requires the accurate identification of the germline genes
      from which a particular sequence is derived. The immunoglobulin heavy-chain
      variable (IGHV) gene repertoire is generally considered to be highly polymorphic.
      In this report, we describe a bioinformatic analysis of germline and rearranged
      immunoglobulin gene sequences which casts doubt on the existence of a substantial
      proportion of reported germline polymorphisms. We report a five-level
      classification system for IGHV genes, which indicates the likelihood that the
      genes have been reported accurately. The classification scheme also reflects the
      likelihood that germline genes could be incorrectly identified in mutated VDJ
      rearrangements, because of similarities to other alleles. Of the 226 IGHV alleles
      that have previously been reported, our analysis suggests that 104 of these
      alleles almost certainly include sequence errors, and should be removed from the
      available repertoire. The analysis also highlights the presence of common
      mismatches, with respect to the germline, in many rearranged heavy-chain
      sequences, suggesting the existence of twelve previously unreported alleles.
      Sequencing of IGHV genes from six individuals in this study confirmed the
      existence of three of these alleles, which we designate IGHV3-49*04, IGHV3-49*05
      and IGHV4-39*07. We therefore present a revised repertoire of expressed IGHV
      genes, which should substantially improve the accuracy of immunoglobulin gene
      analysis.

PMID- 18040281
TI  - Quantitative and qualitative approaches to GOD: the first 10 years of the clonal
      selection theory.
AB  - Of the contentious issues surrounding the clonal selection theory, one of the
      most influential was that of the mechanism for the generation of diversity of
      antibody specificity. While Burnet's qualitative theory assumed a very large
      antibody repertoire, Talmage provided a detailed quantitative argument supporting
      only 5000 individual globulin patterns that provided an antiserum its specificity
      through combinatorial action. This methodological difference between the two men,
      and the mechanistic difference between their models, is key to the understanding
      of the clonal selection theory, its later acceptance and the proportion of credit
      paid to Burnet.

PMID- 18040282
TI  - The evolution of clinical immunology and allergy in Australia.

PMID- 18040283
TI  - Selection, memory and selective memories: T cells, B cells and Sir Mac 1968.

PMID- 18040284
TI  - Autoimmunity since the 1957 clonal selection theory: a little acorn to a large
      oak.
AB  - Knowledge on autoimmunity is examined from the launch of clonal selection theory
      1957-1959. Crucial elements then were 'forbidden clones' of immunocytes as agents
      of tissue damage, somatic mutations that generated such clones and 'homeostatic
      mechanisms' that controlled them. The understanding of autoimmunity over the
      succeeding 50 years has expanded immensely, and many more diseases now come under
      this rubric. Examined here are current problems of definition including
      'adaptive' and 'innate' types of autoimmunity, estimations of population burdens
      of autoimmune diseases, the nature of autoepitopes in the context of the diabetes
      autoantigen GAD65, and the complexities of immune tolerance and the genetic
      influences thereon, leading to the nomination of multiple
      'tolerance/autoimmunity' genes as critical components of pathogenesis. Burnet's
      concept of mutagenesis as a basic feature of various pathologies including
      autoimmunity is given a contemporary focus, his views on deletional tolerance
      have been well vindicated, his 'forbidden clones' remain as unphysiological as
      before albeit phenotypically resembling normal lymphocytes, and his 'homeostatic
      mechanisms' can be now interpreted in terms of immunoregulatory networks.

PMID- 18040285
TI  - Cunning factor: macrophage migration inhibitory factor as a redox-regulated
      target.
AB  - Macrophage migration inhibitory factor (MIF) has an amazing history of
      rediscoveries and controversies surroundings its true biological function. It has
      been classified as a powerful cytokine capable of inducing tumour necrosis factor
      (TNF)-alpha, IL-1beta, IL-6, IL-8, PGE2 along with its ability to override
      glucocorticoid activity in relation to TNF-alpha release from monocytes. However,
      our recent study has failed to reproduce findings on MIF as a factor with
      cytokine-inducing properties but it has confirmed that MIF is capable of inducing
      glucocorticoid-counter regulating activity and amplifying LPS-driven cytokine
      responses. The aim of this review is to analyse the plethora of data surrounding
      MIF not just as a cytokine, but also as a hormone-like molecule, enzyme with
      atypical properties and as a thioredoxin-like protein to address fundamental
      questions about MIF functionality.

PMID- 18040286
TI  - Perlecan: a major IL-2-binding proteoglycan in murine spleen.
AB  - Although interleukin-2 (IL-2) is typically considered a soluble cytokine, our
      laboratory has shown that the availability of IL-2 in lymphoid tissues is
      regulated, in part, by an association with heparan sulfate glycosaminoglycan.
      Heparan sulfate is usually found in proteoglycan form, in which the heparan
      sulfate chains are covalently linked to a specific core protein. We now show that
      perlecan is one of the major IL-2-binding heparan sulfate proteoglycans in murine
      spleen. IL-2 binds perlecan via heparan sulfate chains, as enzymatic removal of
      heparan sulfate from splenic perlecan abolishes its ability to bind IL-2.
      Furthermore, we demonstrate that perlecan-bound IL-2 supports the proliferation
      of an IL-2-dependent cell line. Identification of perlecan as a major heparan
      sulfate proteoglycan that binds IL-2 has implications for both the localization
      and regulation of IL-2 in vivo.

PMID- 18040287
TI  - Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through
      nuclear export.
AB  - p28(GANK) (also known as PSMD10, p28 and gankyrin) is an ankyrin repeat anti
      apoptotic oncoprotein that is commonly overexpressed in hepatocellular carcinomas
      and increases the degradation of p53 and Rb. NF-kappaB (nuclear factor-kappaB) is
      known to be sequestered in the cytoplasm by I kappaB (inhibitor of NF-kappaB)
      proteins, but much less is known about the cytoplasmic retention of NF-kappaB by
      other cellular proteins. Here we show that p28(GANK) inhibits NF-kappaB activity.
      As a nuclear-cytoplasmic shuttling protein, p28(GANK) directly binds to NF
      kappaB/RelA and exports RelA from nucleus through a chromosomal region
      maintenance-1 (CRM-1) dependent pathway, which results in the cytoplasmic
      retention of NF-kappaB/RelA. We demonstrate that all the ankyrin repeats of
      p28(GANK) are required for the interaction with RelA and that the N terminus of
      p28(GANK), which contains the nuclear export sequence (NES), is responsible for
      suppressing NF-kappaB/RelA nuclear translocation. These results suggest that
      overexpression of p28(GANK) prevents the nuclear localization and inhibits the
      activity of NF-kappaB/RelA.

PMID- 18040288
TI  - The transmembrane domain of TACE regulates protein ectodomain shedding.
AB  - Numerous membrane proteins are cleaved by tumor necrosis factor-alpha converting
      enzyme (TACE), which causes the release of their ectodomains. An ADAM (a
      disintegrin and metalloprotease domain) family member, TACE contains several
      noncatalytic domains whose roles in ectodomain shedding have yet to be fully
      resolved. Here, we have explored the function of the transmembrane domain (TM) of
      TACE by coupling molecular engineering and functional analysis. A TM-free TACE
      construct that is anchored to the plasma membrane by a
      glycosylphosphatidylinositol (GPI)-binding polypeptide failed to restore shedding
      of transforming growth factor-alpha (TGF-alpha), tumor necrosis factor-alpha (TNF
      alpha) and L-selectin in cells lacking endogenous TACE activity. Substitution of
      the TACE TM with that of the prolactin receptor or platelet-derived growth factor
      receptor (PDGFR) also resulted in severe loss of TGF-alpha shedding, but had no
      effects on the cleavage of TNF-alpha and L-selectin. Replacement of the TM in TGF
      alpha with that of L-selectin enabled TGF-alpha shedding by the TACE mutants
      carrying the TM of prolactin receptor and PDGFR. Taken together, our observations
      suggest that anchorage of TACE to the lipid bilayer through a TM is required for
      efficient cleavage of a broad spectrum of substrates, and that the amino-acid
      sequence of TACE TM may play a role in regulatory specificity among TACE
      substrates.

PMID- 18040289
TI  - A highly homozygous and parthenogenetic human embryonic stem cell line derived
      from a one-pronuclear oocyte following in vitro fertilization procedure.
AB  - Homozygous human embryonic stem cells (hESCs) are thought to be better cell
      sources for hESC banking because their human leukocyte antigen (HLA) haplotype
      would strongly increase the degree of matching for certain populations with
      relatively smaller cohorts of cell lines. Homozygous hESCs can be generated from
      parthenogenetic embryos, but only heterozygous hESCs have been established using
      the current strategy to artificially activate the oocyte without second polar
      body extrusion. Here we report the first successful derivation of a human
      homozygous ESC line (chHES-32) from a one-pronuclear oocyte following routine in
      vitro fertilization treatment. chHES-32 cells express common markers and genes
      with normal hESCs. They have been propagated in an undifferentiated state for
      more than a year (>P50) and have maintained a stable karyotype of 46, XX. When
      differentiated in vivo and in vitro, chHES-32 cells can form derivatives from all
      three embryonic germ layers. The almost undetectable expression of five
      paternally expressed imprinted genes and their HLA genotype identical to the
      oocyte donor indicated their parthenogenetic origin. Using genome-wide single
      nucleotide polymorphism analysis and DNA fingerprinting, the homozygosity of
      chHES-32 cells was further confirmed. The results indicated that 'unwanted' one
      pronuclear oocytes might be a potential source for human homozygous and
      parthenogenetic ESCs, and suggested an alternative strategy for obtaining
      homozygous hESC lines from parthenogenetic haploid oocytes.

PMID- 18040290
TI  - Diagnosis of pediatric Cushing's syndrome--which test is best?

PMID- 18040291
TI  - Which children with idiopathic short stature should receive growth hormone
      therapy?

PMID- 18040292
TI  - Cascaded synchronization of external-cavity laser diodes.
AB  - An experimental demonstration of optical synchronization of a chain of chaotic
      external-cavity laser diodes is reported for what is believed to be the first
      time. The experiment is performed in the low-frequency-fluctuation regime.

PMID- 18040293
TI  - Microtorus: a high-finesse microcavity with whispering-gallery modes.
AB  - We demonstrate a 165-mu;m oblate spheroidal microcavity with a free spectral
      range of 383.7 GHz (3.06 nm), a resonance bandwidth of 23 MHz (quality factor Q
      approximately 10(7)) at 1550 nm, and finesse F>/=10(4) . The highly oblate
      spheroidal dielectric microcavity combines a very high Q factor, typical of
      microspheres, with a vastly reduced number of excited whispering-gallery modes
      (by 2 orders of magnitude). The very large free spectral range in this novel
      microcavity-a few hundred gigahertz instead of a few gigahertz as in typical
      microspheres-is desirable for applications in spectral analysis, narrow-linewidth
      optical and rf oscillators, and cavity QED.

PMID- 18040294
TI  - Capping layers for extreme-ultraviolet multilayer interference coatings.
AB  - The reflectivity of extreme-ultraviolet thin-film multilayer (ML) interference
      coatings, terminated by a native oxide or other capping layer (CL), is critically
      dependent on the thickness of the final deposited layer of the top period. We
      show in this numerical study that, for a molybdenum-silicon ML, a high
      reflectivity loss may be incurred if the final Si layer is not of optimum
      thickness. For maximum reflectivity the thickness of the final Si layer must be
      controlled such that the node of the standing wave lies within the absorptive
      CL.The final Si layer may be replaced, at the expense of reflectivity, by SiC and
      capped with another inert material for improved protection of the ML.

PMID- 18040295
TI  - Stimulated effects in one-photon resonant interferometric four-wave mixing with
      incoherent light.
AB  - The interferometric four-wave mixing technique with broadband light is extended
      to measurements of population relaxation. For what is believed to be the first
      time, the population relaxation rate in the presence of a pump field is measured.
      It is shown that stimulated emission can significantly affect the results when
      one is dealing with resonant transient wave mixing, and, consequently, in most
      cases stimulated processes should be taken into account.

PMID- 18040296
TI  - Bidirectional, synchronously pumped, ring optical parametric oscillator.
AB  - We report the operation of a bidirectional femtosecond pulsed ring optical
      parametric oscillator based on periodically poled lithium niobate, pumped
      alternately with nonsimultaneous pulses from a Ti:sapphire mode-locked laser. A
      beat note between the two counterpropagating beams attests to a gyro response
      without dead band. The sensitivity of the device to differential phase changes is
      demonstrated by measurement of the nonlinear index of lithium niobate.

PMID- 18040297
TI  - Generation of dual-wavelength pulses by frequency doubling with quasi-phase
      matching gratings.
AB  - We demonstrate generation of two synchronized picosecond pulses at different
      wavelengths near 778 nm by frequency doubling of a femtosecond pulse. We use
      nonlinear frequency filtering with quasi-phase-matching gratings, which allow us
      to obtain second-harmonic spectral intensities that are higher than the spectral
      intensities of the pump.

PMID- 18040298
TI  - Experiments on induced modulational instability of an incoherent optical beam.
AB  - We report the observation of modulational instability (MI) of a partially
      spatially incoherent beam induced by seeding noise through cross-phase
      modulation. We show experimentally that a threshold exists for such induced
      incoherent MI to occur that depends on the degree of spatial coherence as well as
      on the strength of the nonlinearity. Above threshold, the induced MI leads to the
      formation of ordered and disordered patterns of incoherent light.

PMID- 18040299
TI  - Superresolution optical disk with a thermoreversible organic thin film.
AB  - Recording and retrieving small marks far beyond the optical diffraction limit in
      a high-speed rotating phase-change optical disk have been investigated by use of
      a thermoreversible organic thin film as a superresolution mask layer. The organic
      thin film exhibited significant thermoreversibility and rapid response on laser
      irradiation. Recorded marks as small as 120 nm in length could be detected by a
      dynamic disk tester with a laser wavelength of 635 nm and a numerical aperture of
      0.6.

PMID- 18040300
TI  - Femtosecond laser-assisted three-dimensional microfabrication in silica.
AB  - We demonstrate direct three-dimensional (3-D) microfabrication inside a volume of
      silica glass. The whole fabrication process was carried out in two steps:(i)
      writing of the preprogrammed 3-D pattern inside silica glass by focused
      femtosecond (fs) laser pulses and (ii) etching of the written structure in a 5%
      aqueous solution of HF acid. This technique allows fabrication of 3-D channels as
      small as 10mum in diameter inside the volume with any angle of interconnection
      and a high aspect ratio (10mum -diameter channels in a 100mum -thick silica
      slab).

PMID- 18040301
TI  - Optical absorption modeling of thermal infrared detectors by use of the finite
      difference time-domain method.
AB  - The optical absorption of thin-film thermal infrared detectors was calculated as
      a function of wavelength, pixel size, and area fill factor by use of the finite
      difference time-domain (FDTD) method. The results indicate that smaller pixels
      absorb a significantly higher percentage of incident energy than larger pixels
      with the same fill factor. A polynomial approximation to the FDTD results was
      derived for use in system models.

PMID- 18040302
TI  - Continuous-wave broadband emitter based on a transition-metal-ion-doped
      waveguide.
AB  - We demonstrate the suitability of a simple continuous-wave-pumped transition
      metal-ion-doped waveguide as a broadband light source in the wavelength region
      600-1000 nm for interferometric applications. Spatially coherent (single mode in
      the confined direction), spectrally broadband (~130-nm FWHM) luminescence with
      output powers of several hundreds of microwatts is obtained from a Ti:sapphire
      planar waveguide with incident pump powers from an Ar-ion laser of up to 1 W.
      This result represents an increase in power by several orders of magnitude from
      previously reported simple broadband light sources in this wavelength range.

PMID- 18040303
TI  - Quantitative analysis of bending efficiency in photonic-crystal waveguide bends
      at lambda = 1.55 mum wavelengths.
AB  - Based on a photonic-crystal slab structure, a 60 degrees photonic-crystal
      waveguide bend is successfully fabricated. Its bending efficiency within the
      photonic bandgap is measured, and near 100% efficiency is observed at certain
      frequencies near the valence band edge. The bending radius is ~1mum at a
      wavelength of lambda~1.55mum . The measured eta spectrum also agrees well with a
      finite-difference time-domain simulation.

PMID- 18040304
TI  - Measurement of mode-locked laser timing jitter by use of phase-encoded optical
      sampling.
AB  - The phase-noise characteristics of a harmonically mode-locked fiber laser are
      investigated with a new measurement technique called phase-encoded optical
      sampling. A polarization-maintaining ring laser is mode locked by use of the
      short-pulse electrical output of a resonant-tunneling diode oscillator, enabling
      it to produce 30-ps pulses at a 208-MHz repetition rate. The interferometric
      phase-encoded sampling technique provides 60-dB suppression of amplitude-jitter
      noise and allows supermode phase noise to be observed and quantified. The white
      noise pulse-to-pulse timing jitter and the rms supermode timing jitter of the
      laser are measured to be less than 50 and 70 fs, respectively.

PMID- 18040305
TI  - All-solid-state Cr:forsterite laser generating 14-fs pulses at 1.3 mum.
AB  - We report the generation of 14-fs pulses at 1.3mum with 80-mW average power at
      100-MHz repetition rate by an all-solid-state Kerr-lens mode-locked Cr:forsterite
      laser. The laser spectrum covers wavelengths of 1230-1580 nm, with a FWHM of 250
      nm. Since 1.3-mum wavelengths are close to the zero dispersion wavelength of
      Cr:forsterite, higher-order dispersion is the main factor limiting pulse
      durations. We use specially designed and fabricated double-chirped mirrors in
      combination with high-index PBH71 prisms to compensate for the intracavity
      dispersion over almost 300 nm.

PMID- 18040306
TI  - Ultrafast, jitter-free x-ray streak camera that uses single-photon counting.
AB  - A novel method developed to increase the temporal resolution of x-ray streak
      cameras is described. The method is analogous to the time-correlated single
      photon-counting technique, which is commonly used in atomic physics. By use of
      short-pulse x-ray radiation from a laser-produced plasma, generated by an
      ultrafast laser, it is shown that a standard x-ray streak camera with a nominal
      temporal resolution of >5ps can yield a temporal response of 1.6 ps. The readout
      technique also removes temporal jitter with respect to the triggering laser.
      Capabilities and limitations of the technology are discussed.

PMID- 18040307
TI  - Synthesis of periodic femtosecond pulse trains in the ultraviolet by phase-locked
      Raman sideband generation.
AB  - We demonstrate a new technique for femtosecond-pulse generation that employs
      ultrafast modulation of a laser field phase by impulsively excited molecular
      rotational or vibrational motion with subsequent temporal compression. An
      ultrashort pump pulse at 800 nm performs impulsive excitation of a molecular gas
      in a hollow waveguide, and a weak delayed probe pulse at 400 nm is scattered on
      the temporal oscillations of its dielectric index. The resultant sinusoidal phase
      modulation of the probe pulse permits probe pulse temporal compression by use of
      both positively and negatively dispersive elements. The potential of this new
      method is demonstrated by the generation of a periodic train of 5.8-fs pulses at
      400 nm with positive group-delay dispersion compensation.

PMID- 18040308
TI  - Chirped-pulse amplification of ultraviolet femtosecond pulses by use of
      Ce(3+):LiCaAlF(6) as a broadband, solid-state gain medium.
AB  - Chirped-pulse amplification in the ultraviolet region is demonstrated by use of a
      broadband Ce(3+): LiCaAlF(6) laser medium. A modified bow-tie-style four-pass
      amplifier pumped by 100-mJ, 266-nm pulses from a Q -switched Nd:YAG laser has a
      gain factor of 370 and delivers 6-mJ, 290-nm pulses. After dispersion
      compensation, the output pulses can be compressed to 115 fs.

PMID- 18040309
TI  - Femtosecond fiber-feedback optical parametric oscillator.
AB  - We demonstrate what is to our knowledge the first synchronously pumped high-gain
      optical parametric oscillator (OPO) with feedback through a single-mode fiber.
      This device generates 2.3-2.7 W of signal power in 700-900-fs pulses tunable in a
      wavelength range from 1429 to 1473 nm. The necessary high gain was obtained from
      a periodically poled LiTaO(3) crystal pumped with as much as 8.2 W of power at
      1030 nm from a passively mode-locked Yb:YAG laser with 600-fs pulse duration and
      a 35-MHz repetition rate. The fiber-feedback OPO setup is compact because most of
      the resonator feedback path consists of a standard telecom fiber. Because of the
      high parametric gain, the fiber-feedback OPO is highly insensitive to intracavity
      losses. For the same reason, the synchronization of the cavity with the pump
      laser is not critical, so active stabilization of the cavity length is not
      required.

PMID- 18040310
TI  - Precursor experiment for an active true airspeed sensor.
AB  - The feasibility of an active optical true airspeed sensor was demonstrated with a
      coherent short-range Doppler lidar. Even at the long wavelength of 10.6 mum ,
      aerosol events at the high altitude of 12, 000 m were measured. A comparison of
      the line-of-sight velocity obtained by lidar measurements with a conventional
      five-hole probe on an aircraft showed an excellent coincidence in the average
      value, although the lidar detected turbulence effects much more sensitively.

PMID- 18040311
TI  - Measurement of angular distributions by use of low-coherence interferometry for
      light-scattering spectroscopy.
AB  - We present a novel interferometer for measuring angular distributions of
      backscattered light. The new system exploits a low-coherence source in a modified
      Michelson interferometer to provide depth resolution, as in optical coherence
      tomography, but includes an imaging system that permits the angle of the
      reference field to be varied in the detector plane by simple translation of an
      optical element. We employ this system to examine the angular distribution of
      light scattered by polystyrene microspheres. The measured data indicate that size
      information can be recovered from angular-scattering distributions and that the
      coherence length of the source influences the applicability of Mie theory.

PMID- 18040312
TI  - Arbitrary-lattice photonic crystals created by multiphoton microfabrication.
AB  - We used voxels of an intensely modified refractive index generated by multiphoton
      absorption at the focus of femtosecond laser pulses in Ge-doped silica as
      photonic atoms to build photonic lattices. The voxels were spatially organized in
      the same way as atoms arrayed in actual crystals, and a Bragg-like diffraction
      from the photonic atoms was evidenced by a photonic bandgap (PBG) effect.
      Postfabrication annealing was found to be essential for reducing random
      scattering and therefore enhancing PBG. This technique has an intrinsic
      capability of individually addressing single atoms. Therefore the introduction of
      defect structures was much facilitated, making the technique quite appealing for
      photonic research and applications.

PMID- 18040313
TI  - Interrogation of fiber gratings by use of low-coherence spectral interferometry
      of noiselike pulses.
AB  - We demonstrate an innovative method for a real-time interrogation of fiber Bragg
      gratings based on low-coherence spectral interferometry of noiselike pulses. By
      analyzing the spectral interference at the output of a Michelson interferometer
      we obtained the impulse response of the grating with a time resolution of ~350 fs
      . Using the Gabor transformation, we could directly detect nonuniform regions
      inside the grating and could measure the spatial dependence of the resonance
      wavelength along the grating.

PMID- 18040314
TI  - 57-km single-ended spontaneous Brillouin-based distributed fiber temperature
      sensor using microwave coherent detection.
AB  - We present a novel technique for performing single-ended distributed fiber
      temperature measurements by use of microwave heterodyne detection of spontaneous
      Brillouin scattering. Brillouin frequency-shift measurements were obtained for a
      sensing length of 57 km, with a spatial resolution of 20 m. The rms error in
      frequency measurements at the far end of the sensing fiber was less than 3 MHz,
      and the overall frequency dependence on temperature was 1.07+/-0.06 MHz/K.

PMID- 18040315
TI  - Elimination of beam walk-off in low-coherence off-axis photorefractive
      holography.
AB  - Whole-field photorefractive holography can be combined with low-coherence
      interferometry for three-dimensional imaging and other applications, including
      imaging through turbid media, but the off-axis holographic recording geometry
      results in a limited field of view when light of low temporal coherence is used.
      We show that tilting the energy fronts with respect to the wave fronts by use of
      prisms can eliminate this problem and point out that this approach will be useful
      for many linear and nonlinear wave-mixing experiments.

PMID- 18040316
TI  - Diode-pumped regenerative amplifier delivering 100-mJ single-mode laser pulses.
AB  - We report on a side-pumped Nd:phosphate laser regenerative amplifier that
      delivers laser pulses of as much as 100 mJ in a single TEM mode. The laser beam
      is mode matched to the amplification medium by an intracavity fused-silica phase
      plate for mode shaping and a telescope for adjustment of the beam mode to the
      amplification rod section such that most of the energy stored in the rod is
      transferred to the laser pulses. As a result of the good overlap and the low
      loss, an optical-to-optical conversion efficiency of as much as 10% was measured
      for a pumping current of 80 A and greater than 100-mJ output pulses.

PMID- 18040317
TI  - Fourier synthesis of 1.8-THz optical-pulse trains by phase locking of three
      independent semiconductor lasers.
AB  - Fourier synthesis of ultrafast optical-pulse trains was demonstrated based on
      optical phase locking of three independent continuous-wave semiconductor lasers.
      Pulse repetition frequencies as high as 1.81 THz were limited by the gain
      bandwidth of an erbium-doped fiber amplifier. The waveforms of the pulse trains
      were maintained over a long period by use of an auxiliary optical phase-locked
      loop. The repetition frequency could be tuned continuously over a range of 100
      MHz.

PMID- 18040318
TI  - All-fiber passively Q-switched low-threshold erbium laser.
AB  - A novel all-fiber passively Q-switched erbium laser with a Co(2+):ZnSe crystal as
      a saturable absorber is demonstrated experimentally. A pump power threshold of
      20.5 mW, which the authors believe is the lowest to date, has been measured.
      Giant pulses with energy of 3.6 nJ and peak power of 0.7 mW have been obtained.

PMID- 18040319
TI  - Cascade lasing with spherical microparticles.
AB  - Lasing characteristics of dye-doped spherical solid microparticles produced by
      photopolymerization in aerosols are investigated. It is well known that
      dielectric spherical microparticles are optical resonators with very high
      quality. The resonant internal field is not completely confined to the interior
      of the particle. An evanescent wave extends a couple of micrometers into the
      surrounding area. This evanescent field decays exponentially. We demonstrate that
      cascade lasing can be excited by coupling of two spherical microresonators
      through this evanescent field.

PMID- 18040320
TI  - Zeeman laser-scanning confocal microscopy in turbid media.
AB  - A novel Zeeman laser-scanning confocal microscope (ZLSCM) is proposed. It has the
      same configuration as the conventional laser-scanning confocal microscope (LSCM)
      in which a Zeeman laser in conjunction with a Glan-Thompson analyzer is used. In
      our system, the analyzer with the bandpass filter, which act simultaneously as a
      polarization gate and a coherence gate, enhance the collection efficiency of the
      weak-scattering photons and simultaneously suppress the multiple-scattering
      photons. The improvement in depth resolution of a ZLSCM in a scattering medium
      compared with that of a conventional LSCM is discussed and demonstrated
      experimentally.

PMID- 18040321
TI  - Optical parametric amplification in periodically poled KTiOPO(4) seeded by an Er
      Yb:glass microchip laser.
AB  - An optical parametric amplifier based on periodically poled KTiOPO(4) was used to
      generate 3-ns pulses at 1.544 mum . The device was pumped by a Q-switched Nd:YAG
      laser, and the signal output-pulse energy reached 71 muJ ; the maximum gain was
      66 dB. The seed source was an Er-Yb:glass microchip laser. A theoretical fit to
      experimental data gave an effective nonlinear coefficient of 9.7 pm/V , close to
      the highest values reported for periodically poled KTiOPO(4) . Furthermore, the
      broad parametric gain observed could be used for broadband pulse amplification.

PMID- 18040322
TI  - Cross-polarized wave generation by effective cubic nonlinear optical interaction.
AB  - A new cubic nonlinear optical effect in which a linearly polarized wave
      propagating in a single quadratic medium is converted into a wave that is cross
      polarized to the input wave is observed in BBO crystal. The effect is explained
      by cascading of two different second-order processes: second-harmonic generation
      and difference frequency mixing.

PMID- 18040323
TI  - Soliton self-frequency shift in a short tapered air-silica microstructure fiber.
AB  - We report a soliton self-frequency shift of more than 20% of the optical
      frequency in a tapered air-silica microstructure fiber that exhibits a widely
      flattened large anomalous dispersion in the near infrared. Remarkably, the large
      frequency shift was realized in a fiber of length as short as 15 cm, 2 orders of
      magnitude shorter than those reported previously with similar input pulse
      duration and pulse energies, owing to the small mode size and the large and
      uniform dispersion in the tapered fiber. By varying the power of the input
      pulses, we generated compressed sub-100-fs soliton pulses of ~1-nJ pulse energy
      tunable from 1.3 to 1.65 mum with greater than 60% conversion efficiency.

PMID- 18040324
TI  - Raman-excited spin coherences in nitrogen-vacancy color centers in diamond.
AB  - Raman-excited spin coherences were experimentally observed in nitrogen-vacancy (N
      V) diamond color centers by means of nondegenerate four-wave mixing and
      electromagnetically induced transparency. The maximal absorption suppression was
      found to be 17%, which corresponds to 70% of what is possible given the random
      geometric orientation of the N-V center in diamond. In the context of quantum
      computing in solids, this level of transparency represents efficient preparation
      of quantum bits, as well as the ability to perform arbitrary single-quantum-bit
      rotations.

PMID- 18040325
TI  - Low-noise detection of ultracold atoms.
AB  - We have demonstrated a new technique for detecting ultracold atoms. A balanced
      detection technique was used to reduce laser-induced detection noise in
      conjunction with modulation-transfer spectroscopy to distinguish cold atoms from
      a thermal cloud. Using this technique, we have achieved signal-to-noise ratios in
      excess of 2000:1.

PMID- 18040326
TI  - Observation of twin-beam-type quantum correlation in optical fiber.
AB  - We report generation of pulsed twin beams of light through optical parametric
      amplification in a fiber Sagnac loop. By pumping the Sagnac loop with picosecond
      pulses at a wavelength near the zero-dispersion wavelength of the fiber, we
      achieve phase-matched nondegenerate four-wave mixing with gain. For a gain of
      2.2, the intensity noises of the amplified signal and the generated idler
      (conjugate) pulses are found to be correlated by 5.0 dB, and the subtracted noise
      drops below the shot-noise limit by 1.1 dB (2.6 dB when corrected for losses). We
      have investigated the gain dependence of the quantum-noise reduction as well as
      of the intensity noises of the amplified signal and idler pulses. As the gain
      increases, we observe the onset of excess noise on the idler pulses.

PMID- 18040327
TI  - Basic factorization for multilayers.
AB  - We present a factorization scheme that is particularly suited to multilayer
      optics, and we exploit it to develop a consistent description of the action of a
      multilayer in terms of three basic matrices. Connections with equivalent
      behaviors in geometrical optics are discussed.

PMID- 18040329
TI  - Focusing properties of shocking optical pulses.
AB  - We show that optical-cycle steepening in a nonlinear dielectric before focusing
      results in an arbitrarily large enhancement of the focused intensity and energy
      density. The focusing of an optical shock produces singular intensity and energy
      density at the focal point.

PMID- 18040328
TI  - Generation of 5-fs pulses and octave-spanning spectra directly from a Ti:sapphire
      laser.
AB  - Spectra extending from 600 to 1200 nm have been generated from a Kerr-lens mode
      locked Ti:sapphire laser producing 5-fs pulses. Specially designed double-chirped
      mirror pairs provide broadband controlled dispersion, and a second intracavity
      focus in a glass plate provides additional spectral broadening. These spectra are
      to our knowledge the broadest ever generated directly from a laser oscillator.

PMID- 18040330
TI  - Widely tunable pulse durations from a passively mode-locked thin-disk Yb:YAG
      laser.
AB  - We demonstrate a passively mode-locked thin-disk Yb:YAG laser that generates
      solitonlike pulses with durations that are continuously tunable in a very wide
      range from 3.3 to 89 ps or from 0.83 to 1.57 ps. The average powers are typically
      ~12 W . Previously [Opt. Lett. 25, 859 (2000)], only pulse durations in a narrow
      range near 0.7 ps could be obtained from such lasers because of the effect of
      spatial hole burning. We achieved this much wider range by constructing a laser
      cavity with two different angles of incidence on the thin disk, which greatly
      reduces the effect of spatial hole burning.

PMID- 18040331
TI  - Quadrature spectral interferometric detection and pulse shaping.
AB  - We introduce a new variant of spectral interferometry, using spectrally dispersed
      ultrafast laser pulses and quadrature detection to measure optical thickness
      variations related to surface structure. We can resolve surface features with
      depths of 3 mm to 25 nm, using a lateral resolution of ~100mum . Quadrature
      detection gives a larger dynamic range and solves the sign ambiguity problem.
      This method has potential applications in device manufacture, optical
      communications, and error compensation in pulse shaping.

PMID- 18040332
TI  - Nonlinear optical generation and detection of ultrashort electrical pulses in
      transmission lines.
AB  - The nonlinear optical generation and detection of subpicosecond electrical pulses
      on coplanar transmission lines is demonstrated. The electrical pulses are
      generated by optical rectification of ultrashort optical pulses and detected by
      electro-optic sampling. Both processes are the result of a second-order nonlinear
      optical response that occurs in the same poled polymer medium. A bipolar temporal
      waveform with a FWHM duration of 180 fs for the positive lobe that was measured
      after a propagation distance of 125 mum was observed. Pulse broadening was
      minimized by careful attention to the device structure.

PMID- 18040333
TI  - Focusing in microlenses close to a wavelength in diameter.
AB  - Light focused from air into a spherical microlens is affected by diffraction at
      the lens surface as its diameter approaches the wavelength of light. Through an
      extension of Mie theory, we show that a converging wave that is incident upon a
      Si microlens with a diameter less than approximately 4lambda creates a spot as
      much as 25% smaller than predicted with vector diffraction theory. Si microlenses
      only a wavelength in diameter are shown to be virtually insensitive to variations
      in the maximum illumination angle, and changes in index of refraction are not
      found to cause the proportional changes in spot size that would be expected from
      vector diffraction theory.

PMID- 18040334
TI  - Wave-front sensing with time-of-flight phase diversity.
AB  - We present a new way to sense atmospheric wave-front phase distortion. Short
      collimated pulses of laser light at ~350nm are projected from a small auxilliary
      telescope. Rayleigh scattering from each pulse is recorded over a wide range of
      height through the main telescope aperture in a continuous sequence of fast video
      frames by a detector conjugate to mid-height. Phase diversity is thus naturally
      introduced as the pulses approach and pass through focus. We show that an
      iterative algorithm can extract the phase structure from the recorded images and
      do so with a much higher signal-to-noise ratio than is possible with existing
      techniques. If the requirements for real-time data recording and reduction can be
      met, the new method will address the need for tomographic wave-front sensing at
      planned 30-m-class telescopes.

PMID- 18040335
TI  - Orbital angular momentum of partially coherent beams.
AB  - The definition of the orbital angular momentum established for coherent beams is
      extended to partially coherent beams, expressed in terms of two elements of the
      beam matrix. This extension is justified by use of the Mercer expansion of
      partially coherent fields. General Gauss-Schell-model fields are considered, and
      the relation between the twist parameter and the orbital angular momentum is
      analyzed.

PMID- 18040336
TI  - Transport of broadband arbitrary radiation through a bleaching medium.
AB  - A novel analytical treatment of the transport of broadband radiation arbitrarily
      directed through a bleaching medium is presented. The emphasis is on the
      principle features of photodecomposition (bleaching) wave formation. Considering
      radiation from a uniform planar source with stable radiative characteristics and
      media with a uniform initial distribution of the absorptive component, we show
      that this problem has an asymptotic stationary solution for a wave propagating
      through a medium characterized by a photodecomposition spectrum without any
      portion in which the absorption cross section continually runs down to zero.

PMID- 18040337
TI  - Generation of achromatic and propagation-invariant spot arrays by use of
      continuously self-imaging gratings.
AB  - A particular class of Montgomery's self-imaging objects that we call continuously
      self-imaging gratings (CSIG's) is introduced. When they are illuminated by a
      plane wave, these objects produce a field whose intensity profile is a
      propagation- and wavelength-invariant biperiodic array of bright spots. The
      mathematical construction of these objects and their intrinsic properties are
      described. On a practical level, CSIG's are compact and achromatic nondiffracting
      array generators. We show that a good CSIG approximation can be realized by a two
      level phase grating that is experimentally tested.

PMID- 18040338
TI  - Planar holographic optical processing devices.
AB  - Time-domain optical processing implemented through linear spectral filtering
      offers unique potential for future high-bandwidth communications systems. One key
      to realization of this potential is the development of robust, cost-effective,
      fully integrated filtering devices. A new spectral filtering device concept,
      derived from the unique properties of index holograms stamped or otherwise
      written in thin planar waveguide slabs, is described. The holograms that are
      described provide for high-resolution spectral filtering while at the same time
      mapping general input spatial waveforms to desired output waveforms.

PMID- 18040339
TI  - Optimized quantization for diffractive phase elements by use of uneven phase
      levels.
AB  - Many applications of diffractive phase elements involve the calculation of a
      continuous phase profile, which is subsequently quantized for fabrication. The
      quantization process maps the continuous range of phase values to a limited
      number of discrete steps. We present a new scheme with unevenly spaced levels for
      the design of diffractive elements and apply it to the design of intracavity mode
      selecting elements. We show that this modified quantization can produce
      significantly better results than are possible with a regular or even the bias
      phase-optimized quantization scheme that we reported here earlier. In principle
      this process can be employed to a greater or lesser extent in any quantization
      process, allowing the fabrication of diffractive elements with much improved
      performance.

PMID- 18040340
TI  - Compensation of phase change on reflection in white-light interferometry for step
      height measurement.
AB  - We present a method for compensating for the phase change on reflection in
      scanning white-light inteferometry that practically permits precise three
      dimensional profile mapping of composite target surfaces that comprise multiple,
      dissimilar materials. The compensation method estimates the variation of phase
      change with the spectral distribution of the light source through a first-order
      approximation and then directly compensates for the measurement errors by
      performing two additional quasi-monochromatic phase-measuring interferometric
      measurements. Experimental results prove that the proposed compensation method is
      capable of reducing the measurement error in step height gauging to +/-5 nm or
      less.

PMID- 18040341
TI  - Absolute wavelength calibration of pulsed lasers by use of machine vision.
AB  - We developed a new absolute wavelength calibration system that uses machine
      vision for measurement of low-repetition-rate, short-pulse-duration (10-Hz, 5-ns)
      tunable lasers. Weak fluorescence from an iodine cell was measured by use of
      machine vision as a spatially gated integrator, and a pulsed dye-laser wavelength
      was calibrated with an accuracy of +/-0.005 nm , which is precise enough for
      differential absorption lidar application.

PMID- 18040342
TI  - High-conversion-efficiency, diode-pumped continuous-wave Raman laser.
AB  - We demonstrate a diode-pumped cw Raman laser in H(2) with photon-conversion
      efficiency of (66+/-8)%. Pumped by an injection-locked diode laser at 792 nm, the
      Stokes laser produces a peak output power of ~16mW at 1180 nm. Accompanying the
      high Stokes power are deviations from the existing theory, which are believed to
      be caused by the thermal-lensing effect of the Raman gas.

PMID- 18040343
TI  - Spectral hole burning in thulium-doped glass ceramics.
AB  - We have used spectral hole burning to measure the homogeneous linewidth of the
      (3)H(6)(1)- (3)F(3)(1) transition of Tm(3+) ions doped into oxyfluoride glass
      ceramics consisting of nanocrystals of LaF(3) in an aluminosilicate glass matrix.
      From the magnitude of the hole width in the nanocrystals and its dependence on
      temperature, we propose that excitation of tunneling modes in the adjacent glassy
      phase as well as of confined mechanical modes in the nanocrystals is responsible
      for the broadening.

PMID- 18040344
TI  - Polarization gating in ultrafast-optics imaging of skeletal muscle tissues.
AB  - By comparing the results of polarization-dependent, time-resolved intensity
      profiles of photons transmitted through diluted milk, chicken breast tissue, and
      chopped chicken breast tissue, we found that the inherent anisotropic optical
      property of skeletal muscle tissue resulted in coherent coupling between two
      mutually perpendicular polarization directions. This coupling process led to
      difficulty in using the conventional polarization gating method for imaging
      unless the anisotropy characteristics were well understood. However, imaging
      based on polarization gating in diluted milk and chopped chicken breast tissue,
      which had an isotropic random-scattering nature, was quite effective.

PMID- 18040345
TI  - Multipole spatial vector solitons.
AB  - We introduce the concept of multipole spatial optical vector solitons associated
      with higher-order guided modes trapped by a soliton-induced waveguide in a bulk
      medium. Such stationary localized waves include previously predicted vortex- and
      dipole-mode vector solitons and also describe new higher-order vector solitons
      and necklace-type beams. We present the theoretical and experimental results of
      the structure, formation, and instability development of the quadrupole vector
      solitons.

PMID- 18040346
TI  - Electric-field-induced second-harmonic generation in GaN devices.
AB  - Electric-field-induced second-harmonic generation is used to detect electric
      fields in a GaN UV Schottky photodiode and in a GaN light-emitting diode. The
      second-harmonic signal is measured as a function of bias voltage and incident
      laser power. This technique is sensitive to small applied voltages and can be
      used to track electronic waveforms. The photocurrent generated by this technique
      is found to be less than 100 pA when the fundamental and second-harmonic
      frequencies are both below the device bandgap.

PMID- 18040347
TI  - Dynamics of light-induced reflectivity switching in gallium films deposited on
      silica by pulsed laser ablation.
AB  - We present what is to our knowledge the first experimental study of light-induced
      reflectivity changes at an alpha-Ga/Si interface irradiated by femtosecond and
      picosecond laser pulses. After exposure, the reflectivity can increase from
      R?0.55 , which is typical for alpha-Ga , to R?0.8 , which is close to that of
      liquid Ga. The initial step in the reflectivity change of 2-4 ps is resolved with
      150-fs laser pulses. The light-induced reflectivity change relaxes during 100ns
      10 mus , depending strongly on the background temperature of the Ga mirror and
      the laser fluence.

PMID- 18040348
TI  - Volume holographic data storage at an areal density of 250 gigapixels/in.(2).
AB  - One thousand volume holographic data pages, each containing 1x10(6)pixels , are
      stored in a common volume of LiNbO(3) :Fe by use of the 90 degrees geometry. An
      effective transverse aperture of 1.6 mm x 1.6mm , realized by repetition of this
      experiment at each of the eight surrounding locations, results in a demonstrated
      areal density of 394pixels/mum (2) (254 Gpixels/in. (2)) . Short-focal-length
      Fourier optics provide a tightly confined object beam at the crystal; the
      reference beam is angle multiplexed. Data pages retrieved with a 1024 x 1024 CCD
      camera are processed to remap bad spatial light modulator pixels and to
      compensate for global and local pixel misregistration and are then decoded with a
      strong 8-bits-from-12-pixels modulation code. The worst-case raw bit-error rate
      (BER) before error correction was 1.1x10(-3) , sufficient to deliver a user BER
      of 10(-12) at an overall code rate of 0.61 user bits per detector pixel. This
      result corresponds to 1.08% of the well-known theoretical volumetric density
      limit of 1/lambda(3) .

PMID- 18040349
TI  - Fast optical recording in dye-doped polymer-dispersed liquid-crystal films.
AB  - We describe a fast optical recording material based on a dye-doped polymer
      dispersed liquid-crystal film. A holographic grating is written in this film with
      a single Q -switched Nd:YAG laser pulse that has a duration of ~6 ns . Such a
      grating is due to the reorientation effect of the liquid-crystal molecules
      through interaction with the photoinduced adsorption of the doped azo dyes.
      Experimental results indicate that the grating thus formed is permanent but
      electrically switchable.

PMID- 18040350
TI  - Delay in light transmission through small apertures.
AB  - We demonstrate a technique for measuring pulse propagation time delays with 0.5
      fs resolution by use of a widely available 100-fs pulsed laser. Using this
      technique, we measured the time delay of a light pulse transiting through
      subwavelength apertures placed on a 0.3-mum metallic film. We measured a 7-fs
      total transit time, corresponding to an effective group velocity of c/7 . The
      experimental result yielded additional evidence that light interacts resonantly
      with oscillators formed by the surface modes near the small apertures.

PMID- 18040351
TI  - 0.09-terawatt pulses with a 31% efficient, kilohertz repetition-rate Ti:sapphire
      regenerative amplifier.
AB  - We present an efficient, ultrafast regenerate amplifier that increases the energy
      of a laser pulse from 300 pJ to 6 mJ and produces average powers of as much as 9
      W in a TEM(00) spatial mode. As an ultrafast amplifier, the system produces 4-mJ
      pulses with 0.09 TW of peak power.

PMID- 18040352
TI  - Pulse compression without chirp control and frequency detuning by high-order
      coherent Raman scattering in impulsively excited media.
AB  - It is shown that phase-locked pulses as short as 3 fs can be generated by
      coherent scattering in impulsively excited Raman media without the necessity of
      external phase control. The underlying mechanism, temporal characteristics,
      spectra, phase relations, physical limitations owing to competition processes,
      and precompensation of dispersion by the hollow waveguide window are studied
      analytically and numerically without the use of the slowly varying envelope
      approximation and with a global approach to dispersion. Additionally, the large
      frequency shifts in both the Stokes and anti-Stokes directions of as much as half
      the carrier frequency raise the possibility of generating widely tunable
      ultrashort pulses.

PMID- 18040353
TI  - Quasi-linear optical pulses in strongly dispersion-managed transmission systems.
AB  - A unified analytical description of the evolution of quasi-linear optical pulses
      and solitons in strongly dispersion-managed transmission systems is developed.
      Asymptotic analysis of the nonlocal equation that describes the averaged dynamics
      of a dispersion-managed system shows that the nonlinearity decreases for large
      map strength s , as O(log s/s) . The spectral intensity is found to be an
      invariant of the propagation, which allows the phase shift to be computed. These
      findings provide a clear description of pulse propagation in the quasi-linear
      regime, which is characterized by much lower energies than those required for
      stable dispersion-managed soliton transmission with the same dispersion map.

PMID- 18040354
TI  - Adjusting pulse-front tilt and pulse duration by use of a single-shot
      autocorrelator.
AB  - We present a method of adjusting the pulse duration and eliminating the pulse
      front tilt of an ultrashort pulse in real time by use of a specially configured
      single-shot autocorrelator. Pulse-front tilt, or a temporal delay across the
      pulse front, is a common ultrashort-pulse phenomenon when dispersive elements are
      being used. We show the design of an autocorrelator that can be used to eliminate
      the pulse-front tilt and simultaneously adjust the pulse duration in real time by
      adjustment of the pulse compressor of a chirped-pulse amplified laser system.

PMID- 18040355
TI  - High-efficiency, single-stage 7-kHz high-average-power ultrafast laser system.
AB  - We demonstrate a simple and practical single-stage ultrafast laser amplifier
      system that operates at a repetition frequency from 1 to 10 kHz, with millijoule
      pulse energy and as much as 13 W of average power. The repetition rate can be
      adjusted continuously from 1 to 10 kHz by new all-solid-state pump laser
      technology. This is to our knowledge the highest average power ever obtained from
      a single-stage ultrafast laser amplifier system. This laser will significantly
      increase the average power and the repetition rate that is easily accessible for
      high-field experiments such as coherent x-ray generation or for laser-synchrotron
      studies.

PMID- 18040356
TI  - Molybdenum-strontium multilayer mirrors for the 8-12-nm extreme-ultraviolet
      wavelength region.
AB  - Mo-Sr multilayer mirrors were successfully deposited by dc-magnetron sputtering
      and characterized in situ with synchrotron radiation. Normal-incidence (3.6
      degrees ) reflectance of 23.0% at 8.8 nm, 40.8% at 9.4 nm, and 48.3% at 10.5 nm
      were measured before the samples were exposed to air. After exposure, as a result
      of the reactivity of Sr with oxygen and water vapor, the reflectance of these
      multilayers decreased rapidly. Attempts to use thin layers of C to passivate the
      surface of these Mo-Sr multilayers were unsuccessful.

PMID- 18040357
TI  - Comment on Radiative transfer over small distances from a heated metal.

PMID- 18040358
TI  - Comment on Radiative transfer over small distances from a heated metal.
AB  - We show that there is no contradiction between the results presented by Pan [Opt.
      Lett. 25, 369 (2000)] and the 1/L(2) dependence of the radiative energy flux
      between two half-spaces separated by a small vacuum gap of width L obtained by
      Polder and Van Hove [Phys. Rev. B 4, 3303 (1971)] and by Loomis and Maris [Phys.
      Rev. B 50, 18517 (1994)].

PMID- 18040359
TI  - Reply to comments on "Radiative transfer over small distances from a heated
      metal".
AB  - Some previous works showed that radiative transfer between two closely spaced,
      lossy media diverges as 1/L(2), where L is the spacing between the two media.
      This divergent power transfer clearly violates energy conservation. The
      explanation for this unphysical result is that too many optical modes were
      counted in those previous works, and many of those modes are physically
      unattainable. Moreover, many physically significant optical modes were not
      counted in the previous works.

PMID- 18040360
TI  - Physical origin of the Gouy phase shift.
AB  - We show explicitly that the well-known Gouy phase shift of any focused beam
      originates from transverse spatial confinement, which, through the uncertainty
      principle, introduces a spread in the transverse momenta and hence a shift in the
      expectation value of the axial propagation constant. A general expression is
      given for the Gouy phase shift in terms of expectation values of the squares of
      the transverse momenta. Our result also explains the phase shift in front of the
      Kirchhoff diffraction integral.

PMID- 18040361
TI  - Symmetry and degeneracy in microstructured optical fibers.
AB  - The symmetry of an optical waveguide determines its modal degeneracies. A fiber
      with rotational symmetry of order higher than 2 has modes that either are
      nondegenerate and support the complete fiber symmetry or are twofold degenerate
      pairs of lower symmetry. The latter case applies to the fundamental modes of
      perfect microstructured optical fibers, guaranteeing that such fibers are not
      birefringent. We explore two numerical methods and demonstrate their agreement
      with these symmetry constraints.

PMID- 18040362
TI  - Propagation characteristics of a segmented cladding fiber.
AB  - We propose a novel optical fiber design that consists of a uniform core and a
      segmented cladding formed by alternate regions of high and low refractive indices
      in the azimuthal direction. The structure is analyzed by use of the radial
      effective-index method, and the propagation characteristics of the structure are
      studied. The fiber has a highly dispersive cladding and shows characteristics
      similar to those of photonic-crystal fibers and holey fibers. The novel fiber
      offers the possibility of single-mode operation over a wide range of wavelengths
      with a large core diameter.

PMID- 18040363
TI  - Experimental implementation of a Wiener filter in a hybrid digital--optical
      correlator.
AB  - We present the implementation of a clutter-tolerant filter in a hybrid correlator
      system. Wiener filters were mapped with a complex encoding technique onto a
      smectic A(*) liquid-crystal spatial light modulator (SLM). The technique
      overcomes the problem of representing high-dynamic-range data on SLM's that have
      limited modulation capabilities. It also provides a compact image recognition
      system that is robust enough for many real-world applications. Experimental
      results are presented.

PMID- 18040364
TI  - Peering into darkness with a vortex spatial filter.
AB  - I propose to use as a window the dark core of an optical vortex to examine a weak
      background signal hidden in the glare of a bright coherent source. Applications
      such as the detection of an astronomical object, forward-scattered radiation, and
      incoherent light are described whereby signal enhancements of at least 7 orders
      of magnitude may be achieved.

PMID- 18040365
TI  - Determination of the stimulated-emission cross section in an end-pumped solid
      state laser from laser-induced pump saturation data.
AB  - A novel method for the determination of the stimulated-emission cross section in
      an end-pumped solid-state laser is presented. The technique is based on the fact
      that increasing intracavity laser intensity stimulates faster decay of excited
      atoms and reduces the saturation of pump absorption. The use of this laser
      induced pump saturation method is demonstrated with experimental data collected
      from a Cr(4+): YAG laser and analyzed by use of a numerical model that calculates
      the change in the pump transmission as a function of the intracavity laser
      intensity. The predicted cross-section value of 1.1x10(-19)cm(2) agrees well with
      previously reported results.

PMID- 18040366
TI  - Observation of vacuum-ultraviolet Kr(2)* laser oscillation pumped by a compact
      discharge device.
AB  - We have demonstrated vacuum-ultraviolet (VUV) Kr(2) * laser oscillation as a
      result of the realization of a stable self-sustained discharge of high-pressure
      Kr by use of a compact discharge device. Glow discharge was obtained with as much
      as 10 atm of pure Kr. The VUV emission intensity centered at 147.8 nm abruptly
      increased when the charging voltage exceeded a certain value. In addition to this
      threshold behavior, considerable spectral narrowing (4.0?0.4 nm) was observed
      when the charging voltage increased. The maximum output energy at 148 nm was
      150muJ . The gain coefficient was estimated to be 1.1% cm (-1) .

PMID- 18040367
TI  - Vertically coupled GaInAsP--InP microring resonators.
AB  - Vertically coupled microring resonator channel-dropping filters are demonstrated
      in the GaInAsP-InP material system. These devices were fabricated without
      regrowth. In this method, low-loss single-mode waveguides are removed from the
      growth substrate and bonded to a GaAs transfer substrate with benzocyclobutene.
      This permits fabrication of vertically coupled waveguides on both sides of the
      epilayer. Optical quality facets are obtained by cleaving through the transfer
      substrate. Operation of single-mode, single-ring optical channel-dropping filters
      is demonstrated.

PMID- 18040368
TI  - Hybrid glass substrates for waveguide device manufacture.
AB  - Hybrid glass substrates were prepared by a novel, low-temperature process joining
      active (Er-Yb codoped) and passive phosphate glass. The resulting hybrid
      substrates are chemically and physically robust; they can be cut, ground, and
      polished by conventional, water-based techniques. The entire substrate can be
      immersed in a molten-salt bath to produce waveguides simultaneously in the active
      and passive regions. A low reflectance of -34+/-2 dB was measured at the joint
      interface with 1531.2-nm light by optical low-coherence reflectometry. Further, a
      hybrid laser waveguide device exhibited a slope efficiency of 33% at 1540 nm when
      pumped at 975 nm.

PMID- 18040369
TI  - Optical coherence topography based on a two-dimensional smart detector array.
AB  - A low-coherence reflectometer based on a conventional Michelson interferometer
      and a novel silicon detector chip with a two-dimensional array of pixels that
      allows parallel heterodyne detection is presented. We demonstrate acquisition of
      three-dimensional images with more than 100,000 voxels per scan at a sensitivity
      of -58 dB and a rate of 6 Hz.

PMID- 18040370
TI  - Imaging of Ca(2)+ intracellular dynamics with a third-harmonic generation
      microscope.
AB  - We describe the promising development of third-harmonic generation (THG) in laser
      scanning microscopy for study of the functional imaging of live biological cells.
      The dynamics of Ca(2+) in biological cells is shown. The Ca(2+) signal consists
      of a transient increase in the intracellular concentration. THG microscopy allows
      one to temporally visualize the release of Ca(2+) from internal stores and (or)
      calcium influx.

PMID- 18040371
TI  - Quantitative differential phase measurement and imaging in transparent and turbid
      media by optical coherence tomography.
AB  - Differential phase-contrast optical coherence tomography allows one to measure
      the path-length differences of two transversally separated beams in the nanometer
      range. We calculate these path-length differences from the phase functions of the
      interferometric signals. Pure phase objects consisting of chromium layers
      containing steps of approximately 100-200-nm height were imaged. Phase
      differences can be measured with a precision of +/-2 degrees , corresponding to a
      path-difference resolution of 2-3 nm. To investigate the influence of scattering,
      we imaged the phase objects through scattering layers with increasing scattering
      coefficients. The limit of phase imaging through these layers was at
      approximately 8-9 mean free path lengths thick (single pass).

PMID- 18040372
TI  - Observation of self-diffraction by gratings in nematic liquid crystals doped with
      carbon nanotubes.
AB  - Diffraction gratings were studied in cells of the homogeneously aligned liquid
      crystal E7 doped with multiwall carbon nanotubes. These phase gratings were
      induced by interference modulation of two coherent optical beams, in conjunction
      with an applied dc field that was perpendicular to the unperturbed director axis.
      Self-diffraction was observed at all angles of incidence of the writing beams,
      including normal incidence. A superior nonlinear-index coefficient of 5x10(
      2)cm(2)/W was obtained after passage of a 44-mW/cm(2) beam through a film with a
      grating constant of 18 mum under an external voltage of 15 V. The observed
      phenomenon depends strongly on the applied dc field, and the memory effect in a
      nematic film depends strongly on the grating constant.

PMID- 18040373
TI  - Transmission of images through highly nonlinear media by gradient-index lenses
      formed by incoherent solitons.
AB  - We experimentally demonstrate image transmission through a noninstantaneous self
      focusing medium. A partially spatially incoherent soliton is used to form a
      multimode waveguide in a photorefractive crystal, and the modes of that waveguide
      are used to transmit an incoherent image through this nonlinear medium.

PMID- 18040374
TI  - Two-wave mixing of phase-modulated beams in GaP under a dc electric field.
AB  - Two-wave mixing of phase-modulated light beams in crystals of cubic symmetry is
      analyzed on the basis of the vectorial theory of light diffraction. We derive an
      analytical expression for phase-to-intensity transformation in crystals of the
      43m point group of symmetry, which differs from the previously obtained solution
      based on the scalar approach. The most effective transformation is achieved when
      the amplitude of the space-charge-field grating is equal to the quarter-wave
      field. It is shown that the space-charge-field grating created in GaP semi
      insulating crystal at the wavelength of 632 nm is much smaller than can be
      predicted from the one-level band-transport model.

PMID- 18040375
TI  - Higher-order stimulated Brillouin scattering with nondiffracting beams.
AB  - We report on an experimental investigation of stimulated Brillouin scattering
      pumped with a Bessel beam. Owing to the extended interaction length along the
      diffraction-free propagation, higher-order Stokes components are generated in a
      bulk Brillouin-active medium with odd and even orders propagating in opposite
      directions. The spatial, spectral, and temporal properties of the interacting
      waves are discussed.

PMID- 18040376
TI  - Backward supercontinuum emission from a filament generated by ultrashort laser
      pulses in air.
AB  - Backward emission of the supercontinuum from a light filament induced by high
      intensity femtosecond laser pulses propagating in air has been observed to be
      enhanced compared with linear Rayleigh-Mie scattering. This enhancement is
      interpreted as a nonlinear scattering process onto longitudinal refractive-index
      changes induced by the laser pulse itself. The spectral dependence of the
      supercontinuum angular distribution is also investigated.

PMID- 18040377
TI  - Pulsations induced by quantum interference in a microchip solid-state laser
      operating on a ? transiton.
AB  - Self-induced pulsations that are associated with atomic interference have been
      found in a laser-diode-pumped LiNdP(4)O(12) microchip laser with an intracavity
      KTP frequency-doubling crystal operating in a ? scheme. The instability and
      peculiar pulsations that were observed have been verified by a linear stability
      analysis and numerical simulation of two-mode laser equations, including
      nonlinear absorptions of a purely quantum nature and spontaneous-emission noise.

PMID- 18040378
TI  - Efficient collinear fourth-harmonic generation by two-channel multistep cascading
      in a single two-dimensional nonlinear photonic crystal.
AB  - We investigate efficient fourth-harmonic generation in a single two-dimensional
      (2D) quadratically nonlinear photonic crystal. We propose a novel parametric
      process that starts with phase-matched generation of a pair of symmetric second
      harmonic waves, which then interact to produce a fourth-harmonic wave that is
      collinear to the fundamental. We show that this process is more efficient than
      conventional fourth-harmonic-generation schemes by a factor that reaches 4 at low
      intensities and discuss how to design and optimize the nonlinear 2D photonic
      crystals that are implemented in LiNbO(3) and LiTaO(3) .

PMID- 18040379
TI  - Compensation for pixel misregistration in volume holographic data storage.
AB  - We describe what we believe to be a novel postprocessing algorithm for
      compensating for misregistrations between a detector array and the coherent image
      of a pixelated two-dimensional data page. A lookup table of baseline local
      offsets is combined with the dynamically measured global offset of the received
      data page, producing an estimate of the total lateral shift of each small block
      of pixels. A serial algorithm then reallocates the appropriate portion of the
      signal detected by each pixel to its neighbors, accounting for both the linear
      and the quadratic contributions introduced by coherent illumination of square-law
      detectors. This procedure can relax the tight constraints on page registration,
      optical distortion, and material shrinkage that currently hamper page-oriented
      holographic storage systems. Experimental results from a pixel-matched 1-Mpixel
      volume holographic system are presented, showing an increase in position
      tolerance (for a raw bit-error rate <10(-3)) from +/-16% to +/-40% of the pixel
      pitch.

PMID- 18040380
TI  - Critical foliations.
AB  - Critical foliations are special two-dimensional slices (planes of observation) of
      a three-dimensional optical field in which an infinitesimally small change in the
      angle of observation produces major qualitative differences in the observed field
      structure. They are common, but previously unrecognized, features of optical
      fields that contain vortices. An experimentally realizable, on-axis example of
      such a foliation is described for a paraxial Gaussian laser beam.

PMID- 18040381
TI  - Nonlinear absorption by quantum interference in cold atoms.
AB  - We report an experimental observation of third-order nonlinear absorption by
      quantum interference in (87)Rb atoms cooled and confined in a magneto-optic trap.
      A coupling laser creates electromagnetically induced transparency (EIT) in a
      multilevel Rb system in which the third-order nonlinear absorption is enhanced by
      constructive quantum interference while the linear absorption is inhibited by
      destructive interference. Our experiment demonstrates the EIT system proposed by
      Harris and Yamamoto [Phys. Rev. Lett. 81, 3611 (1998)], which absorbs two photons
      but not one photon in the dressed-state picture.

PMID- 18040382
TI  - Dynamic light scattering in localized coherence volumes.
AB  - We introduce a novel light-scattering technique for investigating the dynamics of
      random media with a broad range of optical densities. By use of the spatial
      coherence properties of a single-mode optical fiber and the temporal coherence of
      a broadband source, the measurement volume is isolated at the end of the optical
      waveguide. Optical mixing between the fluctuating scattered light and the Fresnel
      reflected field at the fiber-medium interface is analyzed directly in the
      frequency domain. The unique characteristics of this new technique are discussed
      in the context of simultaneous measurement of average scatterer size and
      concentration in dense colloidal suspensions.

PMID- 18040383
TI  - Terahertz nonlinear optics with strained p-type quantum wells.
AB  - Valence-subband nonparabolicity is shown theoretically to lead to nonlinearities
      associated with terahertz third-harmonic generation in strained p -type quantum
      wells. For strained InAs quantum wells it is found that the corresponding value
      of chi((3)) can be as large as ~10(-12)(m/V)(2). The predicted values of chi((3))
      are in the range of those associated with intersubband transitions in the mid
      infrared region of the spectrum.

PMID- 18040384
TI  - Femtosecond polarization pulse shaping.
AB  - We report computer-controlled femtosecond polarization pulse shaping where
      intensity, momentary frequency, and light polarization are varied as functions of
      time. For the first time to our knowledge, a pulse shaper is used to modulate the
      degree of ellipticity as well as the orientation of the elliptical principal axes
      within a single laser pulse by use of a 256-pixel two-layer liquid-crystal
      display inside a zero-dispersion compressor. Interferometric stability of the
      setup is not required. Complete pulse characterization is achieved by dual
      channel spectral interferometry. This technology has a large range of
      applications, especially in the field of quantum control.

PMID- 18040385
TI  - Generation of 90-nJ pulses with a 4-MHz repetition-rate Kerr-lens mode-locked
      Ti:Al(2)O(3) laser operating with net positive and negative intracavity
      dispersion.
AB  - We demonstrate the generation of high-energy pulses by using a low-repetition
      rate Kerr-lens mode-locked laser. Repetition rates as low as 4 MHz were achieved
      with a long, multiple-pass cavity and a semiconductor saturable Bragg reflector.
      The laser generated pulses of 55-fs duration with a pulse energy of 48 nJ when it
      was mode locked in the net negative dispersion regime. Mode locking in the
      positive dispersion regime reduces instabilities and enables pulses to have
      durations of 80 fs and energies as high as 90 nJ. This is, to our knowledge, the
      highest pulse energy and the lowest repetition rate ever generated directly from
      a femtosecond laser resonator without cavity dumping.

PMID- 18040386
TI  - Generation of tunable narrow-band surface-emitted terahertz radiation in
      periodically poled lithium niobate.
AB  - Generation of tunable narrow-band terahertz (THz) radiation perpendicular to the
      surface of periodically poled lithium niobate by optical rectification of
      femtosecond pulses is reported. The generated THz radiation can be tuned by use
      of different poling periods and different observation angles, limited only by the
      available bandwidth of the pump pulse. Typical bandwidths were 50-100 GHz,
      depending on the collection angle and the number of periods involved.

PMID- 18040387
TI  - Sonoluminescence: nature's smallest blackbody.
AB  - The transduction of sound into light through the implosion of a bubble of gas
      leads to a flash of light whose duration is delineated in picoseconds. Combined
      measurements of spectral irradiance, Mie scattering, and flash width (as
      determined by time-correlated single-photon counting) suggest that
      sonoluminescence from hydrogen and noble-gas bubbles is radiation from a
      blackbody with temperatures ranging from 6000 K (H(2)) to 20,000 K (He) and a
      surface of emission whose radius ranges from 0.1 microm (He) to 0.4 microm (Xe) .
      The state of matter that would admit photon-matter equilibrium under such
      conditions is a mystery.

PMID- 18040388
TI  - Multifractional correlation.
AB  - Multifractional correlation is proposed that is based on a new generalized
      fractional Fourier transform to which we refer as a multifractional Fourier
      transform. The multifractional correlation yields remarkable improvements in the
      correlation output peak intensity, peak sharpness, and light efficiency compared
      with convention correlation, which uses matched and phase-only filters, and still
      maintains better target discrimination capability and a reasonable robustness to
      noise. An optoelectronic hybrid system that can implement the multifractional
      correlation is also suggested.

PMID- 18040389
TI  - Holographic reflection gratings in azobenzene polymers.
AB  - Writing and reading of reflection gratings in films of an azo side-group polymer
      are reported. The gratings were induced holographically by use of an argon-ion
      laser at 488 nm. The measured diffraction efficiency was in the range 2-10%. To
      estimate the scattering of the reflected light within the material, we further
      characterized the gratings by calculating a characteristic transmission. A
      distinct minimum for this transmission was observed, which was redshifted farther
      from the writing wavelength for gratings written in 50-microm polymer samples.

PMID- 18040390
TI  - Narrow-linewidth bandpass filters with diffractive thin-film layers.
AB  - Bandpass filters based on guided-mode resonance effects in waveguide-grating
      structures are obtained by use of a genetic algorithm search-and-optimization
      routine. Calculated examples show that narrow linewidths, high peaks, and low
      sideband transmittances can be achieved in thin-film diffractive devices with few
      layers. A filter with a linewidth of 0.2 nm at a central wavelength of 0.55
      microm is demonstrated in a two-layer-two-grating structure. At 10.6-microm
      wavelength, a filter consisting of a single binary grating is obtained that has a
      linewidth of 12.7 nm and extended, low sideband transmittance. A three-layer
      device with a surface relief Si grating and two underlying homogeneous layers of
      SiO(2) and Si yields a high-efficiency filter centered at 1.55 microm with a
      linewidth of 0.1 nm.

PMID- 18040391
TI  - Polarization beam splitters using polarization diffraction gratings.
AB  - We report a polarization beam splitter that uses polarization gratings written
      onto a zero-twist nematic liquid-crystal display. We show three configurations.
      The first two separate the diffracted light into two orthogonally polarized
      orders that are either linearly or circularly polarized. In the third
      configuration, we demonstrate a novel case for which the output is separated into
      two nonorthonormal polarization states. One component is linearly polarized and
      the second is circularly polarized.

PMID- 18040392
TI  - Distributed pressure sensor with a mode-locked fiber-ring laser.
AB  - We propose and demonstrate a novel distributed fiber-laser pressure sensor. A
      transverse pressure position is located by determination of the free-spectral
      range shift induced by mode coupling in an intracavity polarization-maintaining
      fiber. We demonstrate that the stability and the spatial resolution of the sensor
      can be enhanced drastically by introduction of a novel mode-locking technique.
      Resolution of 54 cm in the 150-m range can be realized.

PMID- 18040393
TI  - Very compact tunable solid-state laser utilizing a thin-film organic
      semiconductor.
AB  - Optically pumped organic semiconductor lasers are fabricated by evaporation of a
      thin film of tris(8-hydroxyquinoline) aluminum (Alq(3)) molecularly doped with a
      laser dye on top of a polyester substrate with an embossed grating structure. We
      achieve low-threshold, longitudinally monomode distributed-feedback laser
      operation. By varying the film thickness of the organic semiconductor film, we
      can tune the wavelength of the surface-emitting laser over 44 nm. The low laser
      threshold allows the use of a very compact all-solid-state pump laser (
      approximately 10 cm long). This concept opens up a way to obtain inexpensive
      lasers that are tunable over the whole visible range.

PMID- 18040394
TI  - Synchronization of high-frequency chaotic optical pulses.
AB  - Synchronization of high-frequency chaotic optical pulses is demonstrated in two
      semiconductor lasers with delayed optoelectronic feedback. The difference between
      synchronization and modulation is discussed. Evidence is presented to show that
      true synchronization, rather than modulation or amplification, is accomplished in
      our optoelectronic feedback system.

PMID- 18040395
TI  - High-repetition-rate, high-average-power, diode-pumped 2.94-microm Er:YAG laser.
AB  - We have demonstrated more than 3 W of average output power from a 2.94-mu;m quasi
      cw diode-pumped total internal reflection (TIR) Er:YAG laser operating at 100 Hz
      with a 4% duty cycle. Moreover, repetition rates of up to 600 Hz at more than 1.2
      W output power have been achieved. The cavity consists of a plane-mirror
      resonator of 40-mm length and uses three of five TIR regions within the laser
      crystal as pump facets to efficiently couple the pump energy into the resonant
      laser mode. Differential efficiencies of up to 18.3% have been achieved at an
      optimum pump pulse width in the range of 300 micros .

PMID- 18040397
TI  - Polarization competition in a quasi-isotropic CO(2) laser.
AB  - We experimentally study the polarization dynamics of a single-mode CO(2) laser
      during the switch-on transient of the laser intensity. We find a strong
      competition between two linearly polarized fields, which finally collapse into a
      single field. As a result of this competition, the two coexisting fields
      oscillate out of phase by pi rad for time intervals much longer than that of the
      relaxation oscillation. One can control the oscillation frequency of the two
      polarized fields by varying the intracavity anisotropies. This phenomenon is
      interpreted in the framework of Maxwell-Bloch equations by addition of nonlinear
      terms to the polarization equations that allow the fields to compete while they
      interact with the same population inversion.

PMID- 18040396
TI  - 28% electrical-efficiency operation of a diode-side-pumped Nd:YAG rod laser.
AB  - We propose a highly efficient quasi-cw Nd:YAG rod laser with a novel side-pumping
      design that uses microlens-free diode stacks. We demonstrate 320-W output power
      with 28% electrical-to-optical efficiency, which is, to our knowledge, the
      highest efficiency reported for diode-pumped solid-state lasers.

PMID- 18040398
TI  - Ultrahigh-resolution optical coherence tomography using continuum generation in
      an air-silica microstructure optical fiber.
AB  - We demonstrate ultrahigh-resolution optical coherence tomography (OCT) using
      continuum generation in an air-silica microstructure fiber as a low-coherence
      light source. A broadband OCT system was developed and imaging was performed with
      a bandwidth of 370 nm at a 1.3-mu;m center wavelength. Longitudinal resolutions
      of 2.5 microm in air and ~2 microm in tissue were achieved. Ultrahigh-resolution
      imaging in biological tissue in vivo was demonstrated.

PMID- 18040399
TI  - Photorefractive BaTiO(3) spheres and spherical disks.
AB  - We have produced single-crystal spheres and spherical disks of photorefractive
      barium titanate (BaTiO(3)) . The spheres and disks allow direct fiber-to-fiber
      two-beam coupling without additional optical elements. We also investigate the
      spontaneous oscillation of triangles and other whispering-gallery modes in these
      spherical structures.

PMID- 18040400
TI  - Generation of sub-6-fs blue pulses by frequency doubling with quasi-phase
      matching gratings.
AB  - We demonstrate the generation of sub-6-fs pulses centered at 405 nm by frequency
      doubling of 8.6-fs Ti:sapphire laser pulses. The frequency doubling is carried
      out in a nonlinearly chirped quasi-phase-matching grating fabricated in a lithium
      tantalate substrate. This device simultaneously provides frequency conversion and
      pulse compression of the positively prechirped fundamental pulses. The second
      harmonic pulses are characterized in a cross-correlation setup, and their pulse
      shapes are retrieved by two iterative phase-reconstruction algorithms. The
      generated second-harmonic spectrum spans a bandwidth of 220 THz. To our
      knowledge, these are the shortest pulses ever generated in the blue spectral
      region.

PMID- 18040401
TI  - Mid-infrared (2.75-6.0-microm) second-harmonic generation in LiInS(2).
AB  - Phase-matched second-harmonic generation is obtained in various LiInS(2) crystals
      by use of the tunable picosecond output of the free-electron laser for infrared
      experiments (FELIX) as the pump source in the mid-IR range from 2.75 to 6.0
      microm. Deviations from the phase-matching curve calculated from Boyd's
      refractive-index data are observed. Furthermore, the optical damage threshold of
      the crystals has been measured to be 1.1. J/cm(2)(>6 GW/cm(2)) at the 5-microm
      wavelength. LiInS(2) holds great promise for parametric interaction in the 1-13
      microm range.

PMID- 18040402
TI  - 92% pump depletion in a continuous-wave one-pump fiber optical parametric
      amplifier.
AB  - Theory shows that near-complete pump depletion can be obtained in uniform fiber
      optic parametric amplifiers (OPA's) for a particular phase-matching condition. We
      have demonstrated 92% pump depletion in a cw fiber OPA, with a 200-mW pump at
      1560 nm in an 11-km-long dispersion-shifted fiber.

PMID- 18040403
TI  - Efficient third-harmonic generation in partly periodically poled KTiOPO(4)
      crystal.
AB  - A partly periodically poled KTiOPO(4) (KTP) crystal has been designed to
      integrate quasi-phase-matched second-harmonic generation (QPM SHG) with sum
      frequency generation in one crystal for generating a third-harmonic beam. The
      highest conversion efficiencies of 45% and 3% have been achieved in our
      experiments for QPM SHG and third-harmonic generation, respectively, by use of
      picosecond laser pulses at 1.327 microm . We have also discovered that
      periodically poled KTP has slightly different indices (n(z)) from bulk KTP.

PMID- 18040404
TI  - All-optical sampling with a monolithically integrated Mach-Zehnder interferometer
      gate.
AB  - An all-optical sampler consisting of a polarization-independent monolithic Mach
      Zehnder interferometer with integrated semiconductor optical amplifiers and a
      temporal resolution of 1 ps is presented. As an example, a simple 320-Gbit/s
      pattern has been successfully sampled, demonstrating the functionality of this
      scheme for high-bit-rate waveform characterizations in light-wave systems.

PMID- 18040405
TI  - Composite optical waveguide composed of a tapered film of bromothymol blue
      evaporated onto a potassium ion-exchanged waveguide and its application as a
      guided wave absorption-based ammonia-gas sensor.
AB  - For what is the first time to our knowledge, we have successfully evaporated a
      tapered film of bromothymol blue (BTB) onto a potassium ion-exchanged (PIE)
      waveguide to form a composite optical waveguide (COWG) for trace-ammonia
      detection. The BTB film has a high refractive index (1.69) and a smooth surface
      and is transparent to a 633-nm laser beam in air. In the COWG structure, the BTB
      film serves as a single-mode waveguide, and adiabatic transition of the TE(0)
      mode was realized between the BTB waveguide and the PIE waveguide with both BTB
      tapers. In the presence of ammonia, the BTB film changes color from yellow to
      blue, which causes absorption of the 633-nm guided wave. Our experimental results
      demonstrate that such a guided wave absorption-based ammonia-gas sensor is much
      more sensitive than one based on evanescent-wave absorption. A detection limit of
      part in 10(9) of ammonia has been realized for a BTB film-PIE glass COWG.

PMID- 18040406
TI  - Multimode resonances in square-shaped optical microcavities.
AB  - Square-shaped two-dimensional optical microcavities (micro-cavities) were
      investigated for possible applications as filters for dense wavelength-division
      multiplexing. Multimode cavity resonances were observed in the elastic scattering
      of approximately 200-microm square-shaped micro-cavities in fused silica. Based
      on a two-dimensional k-space representation, we accounted for the multimode
      spectrum by different normal modes with rays confined by total internal
      reflection. The cavity-mode trajectories need not be closed after each round
      trip. Single-mode spectra are expected from smaller square-shaped micro-cavities.

PMID- 18040407
TI  - Cesium optical atomic clock: an optical pulse that tells the time.
AB  - We propose a new cesium (Cs) atomic clock whose microwave source is a 9.1926-GHz
      harmonically and regeneratively mode-locked erbium fiber laser rather than a
      quartz oscillator and a multiplexer. The repetition rate of the laser is directly
      locked to the Cs resonance, and the frequency stability evaluated by the Allan
      variance is 7.1 x 10(-12) for tau = 1 s. This new atomic clock provides not only
      a precise 1-s time standard after demultiplexing but also an optical pulse train
      with the same stability, which means that the ultrastable clock signal can be
      delivered throughout the world by means of optical fiber networks.

PMID- 18040408
TI  - Nonstationary chaotic oscillations in lasers with frequency-shifted feedback.
AB  - The nonlinear dynamics of lasers with frequency-shifted delayed feedback are
      investigated. Resonant excitation of sustained relaxation oscillations by
      harmonic resonance is demonstrated. Self-induced switching between sustained
      relaxation oscillation and spiking oscillation is observed as the feedback
      coefficient is increased. Observed instabilities are well reproduced by numerical
      simulations of proposed model equations. A statistical analysis of this switching
      phenomenon is carried out numerically, and the results indicate that an inverse
      power relation with the feedback coefficient determines the periods over which
      the system dwells in its relaxation-oscillation state.

PMID- 18040409
TI  - Ultrahigh-resolution spectrometer for the 5-microm wavelength region.
AB  - We present an ultrahigh-resolution saturation spectrometer based on a line
      tunable carbon monoxide laser near 60 THz (lambda = 5 microm). A spectral
      resolution of 14 kHz (Dnu/nu = 2.3 x 10(-10)) for CO fundamental-band transitions
      was achieved, which improves on earlier results by one order of magnitude. A
      frequency-locking scheme using tunable microwave sidebands provides tunability
      and absolute frequency control of the CO laser on the kilohertz. Transit-time
      broadening and pressure broadening of the observed transitions are significantly
      reduced by use of expanded laser beams in a 24-m absorption cell at pressures
      down to 0.0 1Pa. The new spectrometer is suitable for the study of saturation
      line shapes and the development of a new generation of frequency standards in the
      60-THz region.

PMID- 18040410
TI  - Statistical techniques for target detection in polarization diversity images.
AB  - We address the problem of target detection in active polarimetric images. This
      technique, which has the appealing feature of revealing contrasts that do not
      appear in conventional intensity images, provides several images of the same
      scene. However, because of the presence of nonhomogeneity in the reflected
      intensity, it is preferable to perform target detection on the orthogonal-state
      contrast image, which is a measure of the degree of polarization of the reflected
      light when the coherency matrix is diagonal. We show that one can determine a
      simple nonlinear transformation of this orthogonal-state contrast image that
      leads to additive noise, and we then propose a simple and efficient technique for
      detecting targets in these images.

PMID- 18040411
TI  - Third- and fourth-order active dispersion compensation with a phase modulator in
      a terabit-per-second optical time-division multiplexed transmission.
AB  - Broadening of the pulse waveforms by the higher-order dispersion of a
      transmission line is a critical limiting factor in achieving terabit-per-second
      optical time-division multiplexed (OTDM) transmission with femtosecond pulses. We
      show that the third- and fourth-order dispersion of a transmission line can be
      simultaneously compensated for by use of a phase modulator. In this method,
      sinusoidal phase modulation applied to the linearly chirped pulse before
      transmission compensates for the phase shift caused by the third- and fourth
      order dispersion of the transmission line. The pulse broadening of a 380-fs pulse
      after a 70-km transmission in a 1.28-Tbit/s OTDM experiment was as small as 20
      fs.

PMID- 18040412
TI  - Angular spectrum redistribution from a real image of a light as a secondary
      source.
AB  - Coherence theory predicts that the correlation in the fluctuations of a source
      distribution can cause frequency shifts in the spectrum of the emitted radiation,
      even when the source is at rest relative to the observer. Recently we measured
      angular spectrum redistribution, or frequency shifts from a real image of a point
      source, and further verified the coherent interference effect of a finite-band
      source.

PMID- 18040413
TI  - Measurement of positive and negative Goos--Hanchen effects for metallic gratings
      near Wood anomalies.
AB  - Large Goos-Hanchen effects are isolated for reflection on a metallic grating.
      These shifts occur in the vicinity of Wood anomalies. Depending on the nature of
      the anomaly, these displacements are found to be either positive or, contrary to
      the usual GH effect, clearly negative. Those shifts, associated with forward and
      backward leaky surface waves, are as large as plus or minus tens of wavelengths
      for a classic metallic grating.

PMID- 18040414
TI  - Soliton squeezing at the gigahertz rate in a Sagnac loop.
AB  - We demonstrate what is to our knowledge the first all-fiber squeezing experiment.
      A balanced Sagnac loop is used, and a record 6.1+/-0.2dB of noise reduction below
      shot noise has been obtained without stabilization. A gigahertz Er-doped fiber
      laser and a high-power double-clad Er-Yb amplifier have been developed to
      suppress guided acoustic-wave Brillouin scattering and to make possible the all
      fiber configuration.

PMID- 18040415
TI  - Comparison of soliton robustness with respect to polarization-mode dispersion
      with first-order polarization-mode dispersion compensated linear systems.
AB  - Soliton robustness to polarization-mode dispersion (PMD) is compared, both
      analytically and numerically, with that of linear pulses that use first-order PMD
      compensation. It is found that soliton robustness to PMD is comparable with first
      order PMD compensation and in some cases is even better. The effects of soliton
      control methods on soliton robustness to PMD were also investigated, and it was
      found that soliton control methods can significantly improve the soliton's
      robustness to PMD, particularly for long-distance systems.

PMID- 18040416
TI  - Statistics of the Jones matrix of fibers affected by polarization mode
      dispersion.
AB  - We carry out a statistical characterization of Jones matrix eigenvalues and
      eigenmodes to gain deeper insight into recently proposed fiber models based on
      Jones matrix spectral decomposition. A set of linear dynamic equations for the
      Pauli coordinates of the Jones matrix is established. Using stochastic calculus,
      we determine the joint distribution of the retardation angle of the eigenmodes
      and, indirectly, their autocorrelation function. The correlation bandwidth of the
      eigenmodes is found to be radical2/3 that of the polarization mode dispersion
      vector. The results agree well with simulations performed with the standard
      retarded plate model.

PMID- 18040417
TI  - Optical security and encryption with totally incoherent light.
AB  - We present a method for securing and encrypting information optically by use of
      totally incoherent illumination. Encryption is performed with a multichannel
      optical processor working under natural (both temporal and spatially incoherent)
      light. In this way, the information that is to be secured can be codified by use
      of color signals and self-luminous displays. The encryption key is a phase-only
      mask, providing high security from counterfeiting. Output encrypted information
      is recorded as an intensity image that can be easily stored and transmitted
      optically or electrically. Decryption or authentication can also be performed
      optically or digitally. Experimental results are presented.

PMID- 18040418
TI  - Time reversal and object reconstruction with single-cycle pulses.
AB  - We demonstrate the reconstruction of one- and two-dimensional objects by
      numerically backpropagating measured scattered terahertz transients. The spatial
      resolution determined by the Sparrow criterion is found to correspond to
      approximately 30% of the peak wavelength and 85% of the mean wavelength of the
      power spectrum of the single-cycle waveform.

PMID- 18040419
TI  - Small-phase solution to the phase-retrieval problem.
AB  - A solution to the phase-retrieval problem when the unknown phase is small is
      presented. The solution specifies the even and odd parts of the unknown phase in
      two separate equations. The odd part requires a single intensity measurement, and
      the even part requires two measurements. Phase diversity is used for the second
      measurement, and computer simulations are given.

PMID- 18040421
TI  - Effective traveling-wave excitation below the speed of light.
AB  - We demonstrate that effective traveling-wave excitation of high-gain amplifiers
      requires velocities that are remarkably slower than the velocity of light.
      Experiments with a femtosecond-laser-pumped molecular hydrogen laser exhibit
      pronounced enhancement of the intensity if an excitation velocity that is slower
      than the velocity of light is employed. These results are directly scalable to
      shorter wavelengths, paving the way for a more effective pump setup for x-ray
      lasers.

PMID- 18040420
TI  - Phase-dispersion optical tomography.
AB  - We report on phase-dispersion optical tomography, a new imaging technique based
      on phase measurements using low-coherence interferometry. The technique
      simultaneously probes the target with fundamental and second-harmonic light and
      interferometrically measures the relative phase shift of the backscattered light
      fields. This phase change can arise either from reflection at an interface within
      a sample or from bulk refraction. We show that this highly sensitive (~5 degrees
      ) phase technique can complement optical coherence tomography, which measures
      electric field amplitude, by revealing otherwise undetectable dispersive
      variations in the sample.

PMID- 18040422
TI  - Suppression of Q-switch instabilities by feedback control in passively mode
      locked lasers.
AB  - We propose a feedback technique for obtaining stable mode-locked operation in
      lasers that would normally exhibit Q switching. Using the Haus model with
      population dynamics, we examine numerically the case in which the intensity is
      monitored by a slow detector and fed back to the pump power after electronic
      derivation. This approach allows elimination of Q switching in all situations
      considered, in particular, in lasers with a long upper-state lifetime.

PMID- 18040423
TI  - Suppression of the intensity noise of a laser-diode-pumped single-frequency ring
      Nd:YVO(4)-KTP green laser by optoelectronic feedback.
AB  - We investigate the different characteristics of the intensity noise of a laser
      diode-pumped single-frequency ring Nd:YVO (4) laser and a Nd:YVO (4)-KTP green
      laser. By use of an optoelectronic feedback circuit connected directly to the
      pump current of the laser diode, the low-frequency intensity noise of the
      intracavity frequency doubler was suppressed to some extent.

PMID- 18040424
TI  - Longitudinally diode-pumped Nd:YAG double-clad planar waveguide laser.
AB  - We report the demonstration of a near-diffraction-limited, compact, diode-end
      pumped double-clad planar waveguide Nd:YAG laser. Efficient laser operation was
      achieved for the three dominant Nd(3+) transitions, at 1.064, 0.946, and
      1.32microm , with TE polarized output powers of 1.33, 0.57, and 0.33 W for the
      available output couplers. The output beam from the monolithic plane-plane laser
      cavity had measured M(2) values of 1.0 and 1.8 perpendicular and parallel,
      respectively, to the plane of the waveguide.

PMID- 18040425
TI  - Optimization of optode arrangements for diffuse optical tomography: A singular
      value analysis.
AB  - We develope a method to optimize the resolution of diffuse optical tomographic
      instruments. Singular-value analysis of the tomographic weight matrix associated
      with specific data types, geometries, and optode arrangements is shown to provide
      a measure of image resolution. We achieve optimization of device configuration by
      monitoring the resolution measure described. We introduce this idea and
      demonstrate its utility by optimizing the spatial sampling interval and field-of
      view parameters in the parallel-plane transmission geometry employed for diffuse
      optical breast imaging. We also compare resolution in transmission and remission
      geometries.

PMID- 18040426
TI  - Error consideration in contrast-enhanced three-dimensional optical tomography.
AB  - We present three-dimensional tomographic images of the absorption coefficient
      that is due to the presence of a fluorophore reconstructed from frequency domain
      fluence measurements of a tissue phantom containing a single, fluorescence
      contrast-enhanced inclusion. We show that such a reconstruction may be improved
      when the importance of measurement error correlations between relative phase
      shift and amplitude is assessed and when measurements are preprocessed to reduce
      the magnitude and the bias of system error.

PMID- 18040427
TI  - Fundamentals and model of photonic-force microscopy.
AB  - Exact calculations of the near-field electromagnetic force on a nanoparticle
      exerted by the presence of a corrugated dielectric interface are carried out. The
      illumination of this system excites the particle eigenmodes. The calculation is
      two-dimensional, so the nanoparticle is actually a nanocylinder that scans
      parallel to the interface. This system constitutes a model of force transduction
      and surface topography imaging for a photonic-force microscope with signal
      enhancement owing to morphological resonance excitation of the probe.

PMID- 18040428
TI  - High-efficiency parametric oscillation and spectral control in the red spectral
      region with periodically poled KTiOPO(4).
AB  - Narrow-linewidth optical pulses at wavelengths near 630 nm with 2.2-mJ energy
      were generated with 61% efficiency in a periodically poled KTiOPO(4) parametric
      oscillator pumped by a frequency-doubled Q -switched Nd:YAG laser. The tuning
      range was extended to 30 nm by a noncollinear elliptical pumping geometry. We
      demonstrate that by angular dispersion a noncollinear optical parametric
      oscillator can be used to control the spectral and spatial characteristics of the
      output signal beam.

PMID- 18040429
TI  - Hexagonal patterns in multistep optical parametric processes.
AB  - The existence and competition of a novel class of hexagonal patterns in a
      nonlinear optical system are reported. These states are found in a mean-field
      model of a doubly resonant frequency divide-by-3 optical parametric oscillator
      (3omega?2omega+omega) in which the multistep parametric process,
      2omega=omega+omega , is weakly phase matched. A generalized Swift-Hohenberg
      equation and a set of amplitude equations are derived to describe the coexistence
      of hexagonal patterns formed by the superposition of either three or six phase
      locked tilted waves.

PMID- 18040430
TI  - Ultraviolet transparent silicon oxynitride waveguides for biochemical
      microsystems.
AB  - The UV wavelength region is of great interest in absorption spectroscopy, which
      is employed for chemical analysis, since many organic compounds absorb in only
      this region. Germanium-doped silica, which is often preferred as the waveguide
      core material in optical devices for telecommunication, cannot accommodate
      guidance below 400 nm, owing to the presence of UV-absorbing centers. We show
      that silicon oxynitride (SiO(x) N(y)) waveguides exhibit very good UV
      performance. The propagation loss for 24-microm -wide SiO(x)N (y) waveguides was
      found to be ~1.0dB/cm in the wavelength range 220-550 nm. The applicability of
      these waveguides was demonstrated in a biochemical microsystem consisting of
      multimode buried-channel SiO(x)N (y) waveguides that were monolithically
      integrated with microfluidic channels. Absorption measurements of a beta 
      blocking agent, propranolol, at 212-215 nm were performed. The detection limit
      was reached at a concentration of 13microM , with an optical path length of
      500microm (signal/noise ratio, 2).

PMID- 18040431
TI  - Group-velocity-matched three-wave mixing in birefringent crystals.
AB  - It is shown that the combination of pulse-front slant, kappa -vector tilt, and
      crystal birefringence often permits exact matching of both phase and group
      velocities for three-wave mixing in birefringent crystals. This exact match makes
      possible more-efficient mixing of short light pulses, and it permits efficient
      mixing of chirped or broadband light. I analyze this process and present
      examples.

PMID- 18040432
TI  - Transient sum-frequency mixing with temporally tailored laser pulses.
AB  - We discuss the possibility of using temporally tailored pump laser pulses to
      control the temporal width and shape of optical pulses generated in a process of
      transient sum-frequency mixing in crystals with second-order nonlinearity.
      Specific calculations performed in a model crystal in the case of fifth-harmonic
      generation are presented.

PMID- 18040433
TI  - Nanoscopic study of second-harmonic generation in organic crystals with
      collection-mode near-field scanning optical microscopy.
AB  - Collection-mode near-field scanning optical microscopy (NSOM) is used to map
      nanoscopic second-harmonic generation (SHG) in N -(4-nitrophenyl)- (L) -prolinol
      crystals. A spatial resolution of 98 nm is achieved. Near-field polarization
      dependent SHG measurement is performed, and a local effective SHG susceptibility
      of 224+/-18 pm/V is obtained.

PMID- 18040434
TI  - Optical frequency conversion by a rotating molecular wave plate.
AB  - We demonstrate efficient four-wave mixing in low-pressure molecular deuterium
      without the need for phase matching. We use two laser fields with opposite
      circular polarizations to produce a strong excitation of a rovibrational
      transition at a frequency of 3167 cm(-1) . The coherent molecular motion, in
      turn, modulates a third laser field (also circularly polarized) and results in
      highly efficient single-sideband conversion.

PMID- 18040435
TI  - Picosecond time-resolved photoluminescence at detection wavelengths greater than
      1500 nm.
AB  - We report what is to our knowledge the first application of high-efficiency
      InGaAs/InP photon-counting diode detectors in time-resolved photoluminescence
      measurements at wavelength greater than 1500 nm. When they were cooled to 77 K
      and used in conjunction with the time-correlated single-photon counting
      technique, the detectors were capable of an instrumental response of 230 ps and a
      noise equivalent power of 2x10(-17)W Hz(-1/2) . Preliminary measurement of a
      semiconductor heterostructure indicates sensitivity at photogenerated carrier
      densities as low as 10(14)cm (-3) . This development facilitates the detailed
      characterization of dominant recombination mechanisms in semiconductor
      optoelectronic materials and devices designed to operate in the third
      telecommunications spectral window.

PMID- 18040436
TI  - Observation of propagation of surface plasmon polaritons along line defects in a
      periodically corrugated metal surface.
AB  - Propagation of surface plasmon polaritons (SPPs) excited in the wavelength range
      720-830 nm at a corrugated gold-film surface with areas of 150-nm-wide and 45-nm
      high scatterers arranged in a 380-nm-period triangular lattice containing line
      defects is investigated by use of near-field optical microscopy. We demonstrate
      that the SPP at 740-750 nm propagates along 2.2-microm -wide and 16-microm -long
      line defects with ~50% loss, whereas its propagation along narrower line defects
      is strongly damped and in periodically corrugated areas is inhibited. We observe
      significant deterioration of these effects for both longer and shorter
      wavelengths and conclude that the SPP guiding occurs as a result of the SPP
      bandgap effect in the structures.

PMID- 18040437
TI  - Non-Gaussian speckle statistics in adaptive-optics partial compensation.
AB  - Wave fronts distorted by the atmosphere can be partially reconstructed by use of
      adaptive-optics systems. The intensity statistics at the image plane is a
      function of the ratio D/r(0) and of the level of compensation performed by the
      adaptive-optics system. We show that a non-Gaussian statistics is obtained when
      the aperture diameter is slightly greater than the Fried parameter. This
      situation can frequently be found when one is working in the IR. The light
      statistics is obtained by use of a simple model to describe the atmosphere and
      application of the same procedure used in the analysis of scattered light.
      Special attention is paid to very high- and very low-compensation regimes.

PMID- 18040438
TI  - Quality factor for localized defect modes in a photonic crystal slab upon a low
      index dielectric substrate.
AB  - Localized defect modes in a two-dimensional photonic crystal slab upon a SiO(2)
      substrate have been analyzed by a numerical simulation of dipole radiation based
      on the finite-difference time-domain method. A degenerate pair of the defect mode
      of E(1) spatial symmetry was found in a pseudogap in the spectrum of dipole
      radiation. We achieved a quality factor as large as 800 by optimizing the sample
      geometry.

PMID- 18040439
TI  - Coherent broadband pulse shaping in the mid infrared.
AB  - We demonstrate broadband infrared pulse shaping by difference-frequency mixing of
      two visible phase-locked linearly chirped pulses in GaAs. Control of the temporal
      profile of the emitted field is achieved through this direct tailoring of the
      exciting visible intensity. The results are in agreement with a simulation with
      no adjustable parameter.

PMID- 18040440
TI  - Closed-loop adaptive optics in the human eye.
AB  - We have developed a prototype apparatus for real-time closed-loop measurement and
      correction of aberrations in the human eye. The apparatus uses infrared light to
      measure the wave-front aberration at 25 Hz with a Hartmann-Shack sensor. Defocus
      is removed by a motorized optometer, and higher-order aberrations are corrected
      by a membrane deformable mirror. The device was first tested with an artificial
      eye. Correction of static aberrations takes approximately five iterations, making
      the system capable of following aberration changes at 5 Hz. This capability
      allows one to track most of the aberration dynamics in the eye. Results in living
      eyes showed effective closed-loop correction of aberrations, with a residual
      uncorrected wave front of 0.1microm for a 4.3-mm pupil diameter. Retinal images
      of a point source in different subjects with and without adaptive correction of
      aberrations were estimated in real time. The results demonstrate real-time closed
      loop correction of aberration in the living eye. An application of this device is
      as electro-optic "spectacles" to improve vision.

PMID- 18040441
TI  - Switchable optical element with Bragg mode diffraction.
AB  - A theoretical model of a new electronically switchable grating design that uses a
      multilayer structure of an electro-optic (EO) material with an interdigitated
      electrode type of array is proposed as an original technique for calculating the
      induced refractive index. It is shown that asymmetrical distribution of the
      electric field induces a slanted Bragg grating, which allows the slant angle to
      be switched electronically among more than two switching states. Parameters of
      the suggested design are calculated for a number of EO materials. A special case
      of frequency-based switching is anticipated for some polymer-dispersed liquid
      crystal materials.

PMID- 18040442
TI  - 54-fs, 10-GHz soliton generation from a polarization-maintaining dispersion
      flattened dispersion-decreasing fiber pulse compressor.
AB  - A 10-GHz train of nearly transform-limited 54-fs soliton pulses was generated by
      adiabatic compression of the output of a mode-locked fiber laser with a
      polarization-maintaining dispersion-flattened dispersion-decreasing fiber. The
      peak-to-pedestal ratio exceeded 23 dB. At high input powers, the pulse width was
      reduced to as short as 43 fs, although the wings of the pulse were degraded and
      the jitter increased. The compression properties are different for the two
      polarization axes, owing to their different dispersion characteristics. The
      output polarization exhibits no drift.

PMID- 18040443
TI  - Fabrication of long-period fiber gratings by use of focused ion-beam irradiation.
AB  - Long-period gratings have been made in nonphotosensitive optical fibers by
      irradiation of the core of a fiber with a focused beam of high-energy protons.
      The irradiated fibers exhibit relatively low loss, even before thermal annealing,
      and possess strongly wavelength-dependent transmission. The absence of a mask
      provides the opportunity to tailor the grating to a desired profile, and a
      variety of grating profiles were explored. The profile most resembling a sinusoid
      was found to produce the cleanest transmission spectra.

PMID- 18040444
TI  - All-guided stellar interferometer with an integrated optics recombiner.
AB  - We report laboratory tests of an all-guided stellar interferometer used for
      optical aperture synthesis. In anticipation of use of the interferometer in space
      missions, this research is focused especially on compactness of the recombining
      device. The coherent transport and delay lines are implemented with polarization
      maintaining fiber. Beam recombination is achieved by means of an integrated
      optics component. This two-arm interferometer operates at 670-nm mean wavelength
      and allows for a 24-cm correction for the differential air path.

PMID- 18040445
TI  - Fabrication of strong long-period gratings in hydrogen-free fibers with 157-nm F2
      laser radiation.
AB  - Long-period gratings were fabricated in standard telecommunication fiber (Corning
      SMF-28) by use of what is believed to be record short-wavelength light from a 157
      nm F(2) laser. Strong loss peaks were formed without the need for enhancement
      techniques such as hydrogen loading. The magnitude of the attenuation peak was
      sensitive to the single-pulse laser fluence, decreasing with increasing pulse
      fluence as a result of nonuniform 157-nm laser interaction with both the fiber
      cladding and core. The long-period fiber gratings have good wavelength stability
      (Dlambda~7 nm) under thermal annealing at 150 degrees C.

PMID- 18040446
TI  - Sampled fiber Bragg grating for simultaneous refractive-index and temperature
      measurement.
AB  - We present a novel scheme for simultaneous measurement of temperature and
      refractive index by use of a single sampled fiber Bragg grating (SFBG). The
      intrinsic nature of a SFBG that possesses both fiber Bragg grating and long
      period grating spectral responses permits the temperature effect to the measured
      solely from the former, whereas the refractive-index information is extracted
      from the latter. Using such a dual-parameter sensor, we successfully demonstrated
      measurement of the dependence on temperature of the refractive index of an
      aqueous solution of sucrose.

PMID- 18040447
TI  - Nonlinear and noise limitations in dispersion-managed soliton wavelength-division
      multiplexing transmissions with distributed Raman amplification.
AB  - We the study limitations to error-free transmission distance as set by noise
      accumulation and nonlinear pulse interactions in dispersion-managed Nx40-Gbit/s
      transmission systems with either distributed backward Raman amplification or
      lumped erbium-doped fiber amplifiers. Significant performance improvement is
      achievable with Raman amplification.

PMID- 18040448
TI  - Bragg modulational instability induced by a dynamic grating in an optical fiber.
AB  - By means of a dynamic Bragg grating obtained through cross-phase modulation with
      a beating wave in a highly birefringent fiber, we perform a detailed experimental
      study of Bragg modulational instability.

PMID- 18040449
TI  - Co(2+)-doped flatband optical fiber attenuator.
AB  - The attenuation properties of Co(2+) -doped single-mode optical fibers were
      experimentally and analytically investigated for preparation of a stable flatband
      attenuator. By controlling the Co(2+) -doped region in a fiber core, we could
      prepare a flatband attenuator in which the attenuation in wavelengths 1530-1610
      nm was held to within 9.9-10.2 dB (3% variation) and the fluctuation of
      attenuation was less than 0.1 dB with 1-W input power for 100 h.

PMID- 18040450
TI  - Study of angular responses of mixed amplitude--phase holographic gratings:
      shifted Borrmann effect.
AB  - We present theoretical results for angular responses of transmitted and
      diffracted beams in mixed amplitude-phase holographic gratings. Experimental
      results for gratings recorded in photographic emulsions and developed without a
      bleaching bath, with diffraction efficiencies of >20% , are also presented. The
      model shows an angular shift between minimum transmittance and maximum
      diffraction efficiency when both index modulation and absorption coefficient
      modulation are present. Also, the Borrmann effect was found outside the Bragg
      angle. This method can be extended to a study of the mechanism of image formation
      in materials such as bacteriorhodopsin and azo-dye-doped polymers that exhibit
      both types of modulations (index and absorption).

PMID- 18040451
TI  - Reflected image of a strongly focused spot.
AB  - We describe the reflection of a strongly focused beam from an interface between
      two dielectric media. If the beam is incident from the optically denser medium,
      the image generated by the reflected light is strongly aberrated. This situation
      is encountered in high-resolution confocal microscopy and data sampling based on
      solid immersion lenses and oil immersion objectives. The origin of the observed
      aberrations lies in the nature of total internal reflection, for which there is a
      phase shift between incident and reflected waves. This phase shift displaces the
      apparent reflection point beyond the interface, similarly to the Goos-Hanchen
      shift.

PMID- 18040452
TI  - Multilayer mirror for x rays below 190 eV.
AB  - La/B(4)C multilayers have been fabricated by magnetron sputtering for use as x
      ray mirrors at energies below 190 eV, particularly for detection of boron K and
      alpha x rays at 183 eV, their performance has been compared with that of Mo/B(4)C
      multilayers, which are currently the best-performing multilayers for this energy
      range. Transmission electron microscopy and synchrotron soft-x-ray reflectometry
      were used to study the structural quality of the multilayers and their
      performance as x-ray mirrors. The results show a significant improvement of the
      peak reflectivity and the spectral purity, indicating that La/B(4)C has a high
      potential to replace Mo/B(4)C in many x-ray optical applications below 190 eV.

PMID- 18040453
TI  - High-Q concentrated directional emission from egg-shaped asymmetric resonant
      cavities.
AB  - We propose the use of egg-shaped asymmetric resonant cavities (ARCs), each of
      which consists of a half-circular part and a half-deformed part, as promising
      candidates in obtaining desirable whispering-gallery-mode resonances. According
      to numerical analysis based on a ray-optics model, more than an order-of
      magnitude higher Q and more-concentrated emission from the tip of the egg region
      were obtained for egg-shaped ARCs than for the previously studied quadrupolar
      ARCs.

PMID- 18040454
TI  - Intracavity control of a 200-W continuous-wave Nd:YAG laser by a micromachined
      deformable mirror.
AB  - A silicon micromachined membrane deformable mirror with a diameter of 10 mm,
      reflectivity of better than 99.8%, and a surface deflection range of 3mum has
      been used for intracavity control of an industrial 200-W cw Nd:YAG laser. When it
      was placed in the resonator, the mirror demonstrated continuous (more than 40-h)
      stable operation under an ~550-W cw optical load, with beam diameters in the
      range 3-6 mm. Periodic modulation of the curvature of the deformable mirror with
      a frequency of 250 Hz produced quick switching between stable and unstable
      resonator configurations, which resulted in pulse-period Q -switched generation
      with average power in the range 50-200 W, modulation depth from 95% to 10%, and
      an M(2) parameter of 6.5 to 30.

PMID- 18040455
TI  - Laser performance of highly neodymium-doped yttrium aluminum garnet crystals.
AB  - The laser performance of highly neodymium-doped yttrium aluminum garnet (YAG)
      crystals is reported. In cw laser-diode pumping, a slope efficiency of 54% was
      achieved for a 2-at. %-doped sample, which was comparable with the slope
      efficiency of 55% of YVO(4) . The crystal also exhibited a slope efficiency of
      64% under pulsed Ti:sapphire pumping. Such a high efficiency suggests a total
      cavity loss of ~1% , which is as low as that of commercially available 1-at. %
      YAG crystal. The excellent performance of the neodymium-doped YAG crystals
      indicates their high optical quality.

PMID- 18040456
TI  - Ultraviolet lasing in cholesteric liquid crystals.
AB  - We report the observation of stimulated emission and mirrorless lasing in pure
      cholesteric liquid crystals. The lasing action is attributed to the combination
      of the fluorescence and the distributed feedback that are due to the inherent
      periodic structure of the liquid crystal. If the reflection band matches the
      intrinsic emission of the cholesteric liquid crystal, the crystal becomes a
      natural laser material, which will self-lase, without any optical elements or the
      addition of dyes, under picosecond excitation at 355 nm. Samples have been made
      to lase at different wavelengths in the near UV by shifting of the edge of the
      reflection band in the range of 385-405 nm. Typical linewidths observed are of
      the order of 0.5 nm.

PMID- 18040457
TI  - 50-W average-power, 480-fs KrF excimer laser with gated gain amplification.
AB  - We have developed a 50-W average-power KrF excimer laser with a pulse width of
      480 fs by using the method of gated gain amplification at a 200-Hz repetition
      rate.

PMID- 18040458
TI  - Modulational-instability sigma-resonator fiber laser.
AB  - A modulational-instability laser with a resonator in a sigma configuration has
      been developed. The importance of a suitable intracavity filter for removing the
      autocorrelation background of the output signal is shown. A pulse train with a
      repetition rate of 107 GHz determined by the Fabry-Perot etalon used in the
      resonator was obtained at 1.56mum .

PMID- 18040459
TI  - Efficient shortening of self-chirped picosecond pulses in a high-power CO(2)
      amplifier.
AB  - We report a factor-of-6 shortening of the 240-ps (FWHM) pulses in a triple-pass,
      2.5-atm CO(2) amplifier. This technique is based on the self-phase modulation of
      a 10-mum pulse in a plasma after the first pass of amplification, followed by
      narrowing of this chirped pulse during further amplification. Subsequently,
      strong power broadening provides the necessary bandwidth to amplify 40-ps pulses
      to terawatt power levels.

PMID- 18040460
TI  - Sudden chaotic transitions in an optically injected semiconductor laser.
AB  - We study sudden changes in the chaotic output of an optically injected
      semiconductor laser. For what is believed to be the first time in this system, we
      identify bifurcations that cause abrupt changes between different chaotic
      outputs, or even sudden jumps between chaotic and periodic output. These sudden
      chaotic transitions involve attractors that exist for large regions in parameter
      space.

PMID- 18040461
TI  - Nanodissection of human chromosomes with near-infrared femtosecond laser pulses.
AB  - Near-infrared laser pulses of a compact 80-MHz femtosecond laser source at 800
      nm, a mean power of 15-100 mW, 170-fs pulse width, and millisecond beam dwell
      times at the target have been used for multiphoton-mediated nanoprocessing of
      human chromosomes. By focusing of the laser beam with high-numerical-aperture
      objectives of a scanning microscope to diffraction-limited spots and with light
      intensities of terawatts per cubic centimeter, precise submicrometer holes and
      cuts in human chromosomes have been processed by single-point exposure and line
      scans. A minimum FWHM cut size of ~100 nm during a partial dissection of
      chromosome 1, which is below the diffraction-limited spot size, and a minimum
      material removal of ~0.003mum (3) were determined by a scanning-force microscope.
      The plasma-induced ablated material corresponds to ~1/400 of the chromosome 1
      volume and to ~65x10(3) base pairs of chromosomal DNA. A complete dissection
      could be performed with FWHM cut sizes below 200 nm. High-repetition-frequency
      femtosecond lasers at low mean power in combination with high-numerical-aperture
      focusing optics appear therefore as appropriate noncontact tools for
      nanoprocessing of bulk and (or) surfaces of transparent materials such as
      chromosomes. In particular, the noninvasive inactivation of certain genomic
      regions on single chromosomes within living cells becomes possible.

PMID- 18040462
TI  - Initial studies of in vivo absorbing and scattering heterogeneity in near
      infrared tomographic breast imaging.
AB  - Simultaneously recovered absorption and scattering images that separate these
      optical property features within the female breast are demonstrated from
      frequency-domain measurements. A study of known absorbing and scattering objects
      is presented as a foundation for interpreting these in vivo images once the
      contrast space has been fully characterized. No measurable influence of absorbing
      object contrast appears in the scattering images, whereas localized scattering
      contrast enhances the corresponding region within the absorption image by
      approximately 30% (e.g., a 2:1 scatterer also reconstructs as an approximately
      1.3:1 absorber). Scattering and absorption images of a female volunteer with a
      3.4-cm fibroadenoma show a clear 2:1 localized increase in absorption coefficient
      with little or no evidence of scattering enhancement in the lesion.

PMID- 18040463
TI  - Time-gated biological imaging by use of colloidal quantum dots.
AB  - The long (but not too long) fluorescence lifetime of CdSe semiconductor quantum
      dots was exploited to enhance fluorescence biological imaging contrast and
      sensitivity by time-gated detection. Significant and selective reduction of the
      autofluorescence contribution to the overall image was achieved, and enhancement
      of the signal-to-background ratio by more than an order of magnitude was
      demonstrated.

PMID- 18040464
TI  - Three-dimensional resolution enhancement in fluorescence microscopy by harmonic
      excitation.
AB  - A method for increasing lateral as well as axial resolution in fluorescence
      microscopy is presented. A passband with a high cutoff frequency throughout
      reciprocal space can be achieved by illumination of the object with spatially
      harmonic excitation patterns generated by the interference of two collimated
      laser beams. Theoretical calculations show an almost isotropic point-spread
      function with a FWHM near 100 nm.

PMID- 18040465
TI  - Generation of milliwatt narrow-bandwidth vacuum ultraviolet radiation by an all
      solid-state tunable high-average-power laser system.
AB  - Generation of milliwatt narrow-bandwidth vacuum ultraviolet radiation by two
      photon resonant four-wave mixing in Xe at 153 nm is demonstrated. The output of
      extreme ultraviolet radiation was at the microwatt level at 85 nm. For this
      demonstration, we developed an all-solid-state tunable 5-kHz Ti:sapphire laser
      system that produces 0.6-ns 0.7-GHz-bandwidth pulses at an average power of 32 W
      at the fundamental, 12 W at the second harmonic, and 6.3 W at the third harmonic.

PMID- 18040466
TI  - Simultaneous multiwavelength generation from a mode-locked all-solid-state
      Cr:forsterite laser.
AB  - We demonstrate a multiple-channel, mode-locked, all-solid-state Cr:forsterite
      laser. By inserting an etalon into the laser cavity, we have generated 12 phase
      locked channels with 9-19-ps pulse width near 1230 nm with 280-mW average output
      power from a single laser oscillator. By tuning the etalon bandwidth we can
      shorten the pulse width in a specific channel to 1.8 ps.

PMID- 18040467
TI  - Laser-induced quasi-phase matching in thermally poled glasses.
AB  - Quasi phase matching was induced within a few minutes by optical means in a
      thermally poled glass sample. The spatial modulation of chi((2)) that was induced
      by two-photon absorption of the sample subjected to an intense sinusoidal pump
      intensity pattern resulted in a chi((2)) grating. The second-harmonic generation
      produced by a probe beam was diffracted in specific directions by this chi((2))
      grating, thus providing a way to monitor its inscription inside the glass. This
      chi((2)) grating is extremely stable at room temperature and in ambient
      laboratory conditions. During the process of inscription, a linear index grating
      was also induced. It was not stable, and it relaxed rapidly.

PMID- 18040468
TI  - Deterministic vectorial effects lead to multiple filamentation.
AB  - The standard explanation for multiple filamentation of laser pulses is that it is
      caused by noise in the input beam. We propose an alternative explanation that is
      based on deterministic vectorial (polarization) effects. We present numerical
      simulations in support of the vectorial-effects explanation and suggest a simple
      experiment for deciding whether multiple filamentation is due to vectorial
      effects.

PMID- 18040469
TI  - Beamlike twin-photon generation by use of type II parametric downconversion.
AB  - Beamlike twin-photon generation by use of type II spontaneous parametric
      downconversion is demonstrated. The intensity distribution of each beam is round,
      and the emission angle is very small (0.9 degrees ). As a result, a high
      coincidence-count rate per unit of pump power was recorded. The ratio of
      coincidence-count rate to single-count rate was estimated to be 80% in this
      experiment. These features suggest that this method is useful for generation of a
      single-photon state and is applicable to bright, entangled twin-photon sources.

PMID- 18040470
TI  - Undistorted guided-wave propagation of subpicosecond terahertz pulses.
AB  - We report efficient quasi-optic coupling of a freely propagating beam of
      terahertz (THz) pulses into a parallel-plate copper waveguide (with a plate
      separation of 108mum) and subsequent low-loss, single-TEM-mode propagation with
      virtually no group-velocity dispersion. Undistorted, low-loss propagation of the
      incoming 0.3-ps FWHM THz pulses was observed within the bandwidth from 0.1 to 4
      THz for a length of 24.4 mm. We compare experimentally derived values for the
      absorption and phase velocity with theory to show consistency. This demonstration
      is direct proof of the excellent performance of the parallel-plate waveguide as a
      wideband THz interconnect.

PMID- 18040471
TI  - Origin of magnetic field enhancement in the generation of terahertz radiation
      from semiconductor surfaces.
AB  - We present a theory of the magnetic field enhancement of terahertz (THz) emission
      from photogenerated carriers in the surface depletion region of a semiconductor.
      A combination of the Drude-Lorentz model for the carrier dynamics with an
      appropriate solution of the radiation problem is sufficient to explain the strong
      B -field enhancement in THz radiation that has been observed experimentally. The
      effect arises primarily from the increased radiation efficiency of transient
      currents flowing in the plane of the surface. The model provides quantitative
      agreement with experiment for the pronounced angular dependence of the
      enhancement and predicts the correct trend for the enhancement in a variety of
      materials.

PMID- 18040472
TI  - Dynamics of light-induced reflectivity switching in gallium films deposited on
      silica by pulsed laser ablation: errata.

PMID- 18040473
TI  - Trapping and manipulation of low-index particles in a two-dimensional
      interferometric optical trap.
AB  - We demonstrate optical trapping and manipulation of low-index spheres in two
      dimensions, using the pattern produced by two interfering plane waves. This
      technique shows, for what is believed to be the first time, alignment of an array
      of hollow spheres and simultaneous manipulation of high- and low-index particles
      in the horizontal plane. Furthermore, rodlike particles (up to 30microm in
      length) are manipulated simultaneously with the low-index particles. This
      technique offers a practical method for manipulating bubbles, low-index droplets,
      or rodlike biological samples.

PMID- 18040474
TI  - Chaotic on off keying for secure communications.
AB  - We experimentally demonstrate a chaotic on-off keying method for secure
      communications by using chaos synchronization in two microchip lasers. The output
      of the microchip laser in the transmitter is externally modulated with an acousto
      optic modulator at ~4 MHz . One encodes a digital message in the chaotic carrier
      by turning the modulation on and off at 100 kHz. Because the accuracy of
      synchronization for the slave laser in the receiver tends to be degraded in the
      presence of external modulation in the injection laser signal, one can
      distinguish two binary states. The digital message can be recovered as an
      envelope of the chaotic oscillation when the difference between the two laser
      outputs of the transmitter and the receiver is calculated.

PMID- 18040475
TI  - Spectral hole in the amplified spontaneous emission spectrum of a fiber optical
      parametric amplifier.
AB  - The amplified spontaneous emission (ASE) spectrum of a fiber optical parametric
      amplifier in a gain-saturation condition is studied. We experimentally observed
      holes around the signal and the idler in the ASE spectrum of a deeply gain
      saturated amplifier. This observation is explained by a theoretical model that
      includes parametric interactions among ASE components and the pump, signal, and
      idler beams.

PMID- 18040476
TI  - Optimized absorption in a chaotic double-clad fiber amplifier.
AB  - Double-clad fibers with a doped single-mode core and a noncylindrical multimode
      chaotic cladding are shown to provide optimal pump-power absorption in power
      amplifiers. Based on the chaotic dynamics of rays in such fibers, we propose a
      quantitative theory for the pump-absorption ratio and favorably compare the
      predictions of the theory with numerical results obtained through an adapted beam
      propagation scheme.

PMID- 18040477
TI  - Electronic imaging using a logarithmic asphere.
AB  - Transmission functions are derived that are valid in the nonparaxial case for a
      class of lenses that will image a continuum of points along an optical axis to a
      single image point. This lens, which we call a logarithmic asphere, is then used
      in a digital camera. The resolution of the camera is limited by the pixel size of
      the CCD; i.e., it is not diffraction limited. Digital processing is used to
      recover the image, and image-plane processing is used for speed. We find a
      tenfold increase in the depth of field over that for the diffraction-limited
      case.

PMID- 18040479
TI  - Continuous-wave and passively Q-switched cladding-pumped planar waveguide lasers.
AB  - Greater than 12 W of average output power has been generated from a diode-pumped
      Yb:YAG cladding-pumped planar waveguide laser. The laser radiation developed is
      linearly polarized and diffraction limited in the guiding dimension. A slope
      efficiency of 0.5 W/W with a peak optical-optical conversion efficiency of 0.31
      W/W is achieved. In a related structure, greater than 8 W of Q -switched average
      output power has been generated from a Nd:YAG cladding-pumped planar waveguide
      laser by incorporation of a Cr(4+): YAG passive Q switch monolithically into the
      waveguide structure. Pulse widths of 3 ns and pulse-repetition frequencies as
      high as 80 kHz have been demonstrated. A slope efficiency of 0.28 W/W with a peak
      optical-optical conversion efficiency of 0.21 W/W is achieved.

PMID- 18040478
TI  - Compact 3-dB tapered multimode interference coupler in silicon-on-insulator.
AB  - We have fabricated a compact 3-dB multimode interference coupler with a large
      silicon-on-insulator cross section. To reduce the length of the usual symmetric
      interference multimode interference coupler, we propose using a parabolically
      tapered structure. The length of the device is 398microm . The device has a
      uniformity of 0.28 dB.

PMID- 18040480
TI  - Highly efficient hybrid fiber taper coupled microsphere laser.
AB  - A novel hybrid fiber taper is proposed and demonstrated as the coupler in a
      microsphere laser system. The pump wave and the laser emission, respectively, are
      more efficiently coupled to and from the sphere modes with this taper structure.
      A 980-nm pumped erbium-ytterbium codoped phosphate microsphere laser is
      demonstrated in the 1550-nm band. As much as 112microW of single-frequency laser
      output power was measured, with a differential quantum efficiency of 12%.

PMID- 18040481
TI  - Photoacoustic spectroscopy with quantum cascade distributed-feedback lasers.
AB  - We present photoacoustic (PA) spectroscopy measurements of carbon dioxide,
      methanol, and ammonia. The light source for the excitation was a single-mode
      quantum cascade distributed-feedback laser, which was operated in pulsed mode at
      moderate duty cycle and slightly below room temperature. Temperature tuning
      resulted in a typical wavelength range of 3cm(-1)at a linewidth of 0.2cm(-1). The
      setup was based on a Herriott multipass arrangement around the PA cell; the cell
      was equipped with a radial 16-microphone array to increase sensitivity. Despite
      the relatively small average laser power, the ammonia detection limit was 300
      parts in 10(9)by volume.

PMID- 18040482
TI  - Microscope-based static light-scattering instrument.
AB  - We describe a new design for a microscope-based static light-scattering
      instrument that provides simultaneous high-resolution images and static light
      scattering data. By correlating real space images with scattering patterns, we
      can interpret measurements from heterogeneous samples, which we illustrate by
      using biological tissue.

PMID- 18040483
TI  - Experimental three-dimensional fluorescence reconstruction of diffuse media by
      use of a normalized Born approximation.
AB  - We present a normalized Born expansion that facilitates fluorescence
      reconstructions in turbid, tissuelike media. The algorithm can be particularly
      useful for tissue investigations of fluorochrome distributionin vivo, since it
      does not require absolute photon-field measurements or measurements before
      contrast-agent administration. This unique advantage can be achieved only in
      fluorescence mode. We used this algorithm to three-dimensionally image and
      quantify an indocyanine fluorochrome phantom, using a novel fluorescence
      tomographic imager developed for animals.

PMID- 18040484
TI  - Studies of the fifth-order nonlinear susceptibility of ultraviolet-grade fused
      silica.
AB  - Femtosecond transient absorption pump-probe spectroscopy has been used to study
      the third- and fifth-order nonlinear susceptibility of UV-grade fused silica.
      Theoretical simulations support the experimental evidence of interference between
      the third- and fifth-order contributions to the signal. Approximate values of the
      second-order nonlinear refractive index n(4) and of the three-photon absorption
      coefficient gamma are obtained.

PMID- 18040485
TI  - Third-harmonic generation in a general two-component quasi-periodic optical
      superlattice.
AB  - The quasi-periodic optical superlattice is a promising material for use in
      optical frequency conversion. We propose a method for designing a quasi-periodic
      structure for efficient third-harmonic generation (THG) at any given wavelength.
      With this method we have made a LiTaO(3) sample in which 27% THG at 0.48microm
      was achieved, together with a series of highly efficient multiwavelength second
      harmonic generation outputs. The result is in good agreement with the theoretical
      prediction.

PMID- 18040486
TI  - Self-phase modulation in polydiacetylene single crystal measured at 720-1064nm.
AB  - Detailed measurement of spectral broadening in a poly-[2, 4 hexadiyne-1, 6 diol
      bis-(p -toluene sulfonate)] (PTS) single crystal owing to self-phase modulation
      was performed as a function of wavelength by use of a Ti:sapphire laser producing
      200-fs pulses at 720-920 nm and a Nd:YAG laser producing 50-ps pulses at 1064 nm.
      The nonlinear refractive index (n(2)) of PTS at these wavelengths was determined
      from the measured phase shift. Group-velocity dispersion was estimated and found
      to have a negligible effect on the observed spectral broadening. The two-photon
      absorption coefficient (alpha(2)) over this wavelength range was determined from
      nonlinear transmission measurements. The largest magnitude of n(2) observed at
      720 nm was 3.9x10(-5)cm (2)/MW . The results show that the magnitude of n(2)
      monotonically decreases as wavelength is increased away from resonance, and two
      photon absorption does not make a significant contribution to n(2) at off
      resonant wavelengths up to 1064 nm.

PMID- 18040487
TI  - Experiments in quadratic spatial soliton generation and steering in a
      noncollinear geometry.
AB  - Generation of spatial solitons with noncollinear excitation beams was
      experimentally investigated for type II second-harmonic generation in KTP.
      Spatial switching at a distance of 220microm and steering in a 330-microm range
      were demonstrated. Changes in soliton behavior induced by modification of the
      phase-matching condition (and) or by an imbalance of the inputs at the
      fundamental frequency have been characterized.

PMID- 18040488
TI  - Anisotropic charge displacement supporting isolated photorefractive optical
      needles.
AB  - Strong asymmetry in the charge distribution supporting a single noninteracting
      spatial needle soliton in a paraelectric photorefractive is directly observed by
      means of electroholographic readout. Whereas in trapping conditions a quasi
      circular wave is supported, the underlying double-dipolar structure can be made
      to support two distinct propagation modes.

PMID- 18040490
TI  - Photoinduced stable second-harmonic generation in chalcogenide glasses.
AB  - We report on photoinduced second-harmonic generation (SHG) in chalcogenide
      glasses. Fundamental and second-harmonic waves from a nanosecond pulsed Nd:YAG
      laser were used to induce second-order nonlinearity in chalcogenide glasses. The
      magnitude of SHG in 20G?20A?60S glass was 10(4) larger than that of tellurite
      glass with a composition of 15Nb(2)O (5) 85TeO(2) (mol.%). Moreover, no apparent
      decay of photoinduced SHG in 20G?20A?60S glass was observed after optical poling
      at room temperature. We suggest that the large and stable value of chi((2)) is
      due to the induced defect structures and large chi((3)) of the chalcogenide
      glasses.

PMID- 18040489
TI  - Self-trapping of bright rings.
AB  - We present experimental observations of self-trapped rings carrying zero
      topological charge, along with simulations that display the self-focusing
      dynamics of the rings and their stability features in materials with saturable
      nonlinearities.

PMID- 18040491
TI  - Synthesis of a parallel-coupled ring-resonator filter.
AB  - An effective and exact synthesis technique for the design of parallel-coupled
      ring-resonator filters with a maximally flat stop-band characteristic of any
      order is presented. Simple closed-form formulas determine the Q factor of each
      resonator and the coupling coefficients. The performances of these filters are
      discussed for their applications as interleavers and channel-dropping filters in
      wavelength-division multiplexing systems.

PMID- 18040492
TI  - Dynamic complex wave-front modulation with an analog spatial light modulator.
AB  - A method of producing an arbitrary complex field modulation by use of two pixels
      of an analog ferroelectric spatial light modulator (SLM) is demonstrated. The
      method uses the gray-scale modulation capabilities of a SLM to spatially encode
      the complex data on two pixels. A spatial filter is used to remove the carrier
      signal. This technique gives fast gray-level amplitude and phase modulation.

PMID- 18040494
TI  - Diode-laser noise conversion in an optically dense atomic sample.
AB  - We report on oscillating complex noise spectra obtained when a diode-laser beam
      passes through a resonant dense Doppler-broadened cesium-vapor cell. Atomic
      coherence converts the laser phase noise into amplitude noise in the transmitted
      beam. We have found that the level of amplitude noise is orders of magnitude
      above the intrinsic laser noise. As a function of laser detuning, this noise
      extends over several inhomogeneous widths, depending on the spectral frequency.
      Numerical calculations based on a simple theory remarkably mimic the details of
      the experimental noise spectra.

PMID- 18040493
TI  - Cavity-damping-induced transitions in a driven atom- cavity system.
AB  - We investigate the fluorescence spectrum of a two-level atom in a cavity when the
      atom is driven by a classical field. We show that forbidden dipole transitions in
      the Jaynes-Cummings ladder structure are induced in the presence of cavity
      damping, which deteriorates the degree of otherwise perfect destructive
      interference among the transition channels. With the larger cavity decay, these
      transitions are more enhanced.

PMID- 18040495
TI  - Use of a graded gain random amplifier as an optical diode.
AB  - The spectral characteristics of liquid amplifying media have been used to design
      and experimentally realize an optical device that prevents the propagation of a
      band of wavelengths in one direction and permits it in the opposite direction,
      thus acting as an optical diode. The addition of random scattering centers is
      shown to narrow the width of the forbidden band. A model is proposed to explain
      the observations and is verified by Monte Carlo simulations.

PMID- 18040496
TI  - Highly simplified device for ultrashort-pulse measurement.
AB  - We show that a frequency-resolved optical gating device using (1) a thick
      nonlinear crystal to replace the usual thin crystal and spectrometer and (2) a
      Fresnel biprism to replace the beam splitter and delay line yields a remarkably
      simple single-shot ultrashort-pulse intensity-and-phase measurement device with
      no sensitive alignment parameters and significantly greater sensitivity.

PMID- 18040497
TI  - Generation of high-energy femtosecond pulses in multimode-core Yb-fiber chirped
      pulse amplification systems.
AB  - 220-fs pulses with energies of ~100microJ have been generated by use of two
      different configurations of diode-pumped Yb-fiber chirped-pulse amplification
      systems. Energy scaling was demonstrated with 25-microm -core diameter fibers, in
      which stable diffraction-limited output (M(2)~1.1) was achieved. A two-stage
      fiber-amplifier system produced average powers of up to 5.5 W at ~1- MHz pulse
      repetition rate. A double-pass configuration provided 53-dB gain in a single Yb
      fiber amplifier stage, thus eliminating the necessity for multiple amplification
      stages as well as the need for using polarization-preserving fibers.

PMID- 18040498
TI  - Adaptive control of femtosecond pulse propagation in optical fibers.
AB  - Nonlinear effects present fundamental obstacles to the propagation of femtosecond
      pulses of detectable energy in single-mode optical fibers, inducing severe
      distortion even after a very short (a few meters) propagation distance. We show
      here that adaptive pulse shaping can overcome these limitations by synthesizing
      pulses that are self-correcting for higher-order nonlinear effects when they are
      launched in the fiber. This approach would not only affect optical communications
      but also yield benefits in various disciplines requiring optimized fiber-based
      femtosecond pulse delivery, for example, nonlinear imaging techniques such as
      multiphoton microscopy, material processing, and medical diagnostics.

PMID- 18040499
TI  - Continuous-wave operation and Q-switched mode locking of Cr(4+):YAG microchip
      lasers.
AB  - Cw-operation, gain-switched, and passively Q -switched mode locking of Cr(4+):
      YAG microchip lasers with output powers of several hundred milliwatts is
      demonstrated experimentally in the eye-safe region near 1.5microm . Requirements
      for cw mode locking of such lasers are investigated by numerical simulations.

PMID- 18040500
TI  - Effect of group-delay ripples on dispersion-managed soliton communication systems
      with chirped fiber gratings.
AB  - The effect of group-delay ripples in dispersion-managed soliton communication
      systems that use chirped fiber gratings for dispersion compensation is studied.
      Using both a reduced model and direct numerical simulation, we find that
      dispersion-managed solitons exist even in the presence of large dispersion
      variation caused by group-delay ripples. The dispersion-managed solitons suppress
      the growth of intersymbol interference induced by the group-delay ripples.

PMID- 18040501
TI  - Measurement of birefringence correlation length in long, single-mode fibers.
AB  - Measurements of birefringence correlation length performed on long single-mode
      telecommunication fibers are reported. The proposed technique relies on the
      statistical properties of the backscattered-field polarization, which was
      measured by means of a polarization-sensitive optical time-domain reflectometer.
      Experimental results are reported that show good agreement with the underlying
      theory based on stochastic differential equations.

PMID- 18040502
TI  - Interactions of dispersion-managed solitons in wavelength-division-multiplexed
      optical transmission lines.
AB  - We investigate interactions between pulses in dispersion-managed multichannel
      wavelength-division-multiplexed soliton systems, using an improved variational
      approximation. The frequency shifts are found to be smallest for moderate, i.e.,
      relatively short-scale, dispersion management. The position shifts increase
      monotonically with map strength.

PMID- 18040503
TI  - Wigner function for highly convergent three-dimensional wave fields.
AB  - The angle-impact Wigner function for highly convergent three-dimensional scalar
      wave fields is derived directly by use of the three-dimensional generalized
      optical transfer function rather than from a six-dimensional Wigner function. The
      angle-impact Wigner function is a real four-dimensional function from which the
      intensity at any point in space is readily determined.

PMID- 18040504
TI  - Achromatic polarization-preserving beam displacer.
AB  - We present a novel device based on four orthogonal reflections that displaces an
      optical beam while preserving the state of polarization. The principle of
      operation is the overall compensation of the phase shifts that s and p
      polarization components of the light acquire at each reflection. This
      compensation, which relies on the use of four identical reflectors, is
      independent of the actual values of the s and p reflection coefficients and thus
      is independent of the wavelength. Measurements of the polarization-preserving
      properties with different sets of reflectors and tolerances to misalignments are
      presented.

PMID- 18040505
TI  - Correct-image reconstruction in the presence of severe anamorphism by means of
      digital holography.
AB  - It is demonstrated for the first time to the authors' knowledge that digital
      holographic image reconstruction can be applied to correction of image
      reconstruction in the presence of severe anamorphism and aberrations. It is shown
      that anamorphism and aberrations can be taken into account and compensated for
      separately to yield a correct-image reconstruction. Anamorphism and aberrations
      are introduced by a holographic recording system based on a reflective grating
      interferometer (RGI). The strong anamorphic behavior of the RGI prevents
      reconstruction of a correct image unless that behavior is compensated for in the
      process of numerical holographic reconstruction.

PMID- 18040507
TI  - Combined phase locking and beam shaping of a multicore fiber laser by structured
      mirrors.
AB  - We present a novel mirror geometry combining the two features of phase locking
      and simultaneous beam shaping of the emission of a multicore fiber (MCF) laser.
      In the experiments we applied a Talbot cavity to a diode-pumped MCF laser with 18
      microcores placed on a ring. The feedback mirror consisted of a highly reflecting
      structure with 18 spokes and a circle in the center deposited on a glass
      substrate. The spokes increased the discrimination between the supermodes and
      suppressed independent lasing of the individual emitters. The central dot caused
      strong diffraction of the output radiation, leading to a shaped beam profile. The
      output power of the phase-locked MCF laser exceeded 5 W.

PMID- 18040508
TI  - Intracavity LiNbO(3) Fabry-Perot etalon for frequency stabilization and tuning of
      a single-mode quasi-continuous-wave titanium:sapphire ring laser.
AB  - We describe an intracavity LiNbO(3) Fabry-Perot etalon for frequency
      stabilization and tuning of a single-mode quasi-continuous-wave Ti:Al(2)O (3)
      ring laser. Taking into account the 150-micros pulse duration and the 40-Hz
      repetition rate of our laser, we achieve stabilization by 266-kHz modulation of
      100-V peak-to-peak voltage applied to the electro-optic crystal. Tuning is
      ensured by the presence of a gain loop that contains a lock-in amplifier reacting
      with a multimorphous ceramic by means of 0-300-V dc voltage, which causes slight
      rotation of the LiNbO(3) Fabry-Perot etalon. A continuous frequency scan of 6 GHz
      was made that potentially can be extended to 6 cm(-1) .

PMID- 18040506
TI  - Minimal-complexity segmentation with a polygonal snake adapted to different
      optical noise models.
AB  - Polygonal active contours (snakes) have been used with success for target
      segmentation and tracking. We propose to adapt a technique based on the minimum
      description length principle to estimate the complexity (proportional to the
      number of nodes) of the polygon used for the segmentation. We demonstrate that,
      provided that an up-and-down multiresolution strategy is implemented, it is
      possible to estimate efficiently this number of nodes without a priori knowledge
      and with a fast algorithm, leading to a segmentation criterion without free
      parameters. We also show that, for polygonal-shaped objects, this new technique
      leads to better results than using a simple regularization strategy based on the
      smoothness of the contour.

PMID- 18040509
TI  - Yb:YAG and Nd:YAG edge-pumped slab lasers.
AB  - Experimental demonstrations of two edge-pumped zigzag slab lasers are presented.
      The Nd:YAG slab laser generated 127 W of multimode output power with 300W of pump
      power. Preliminary results with a Yb:YAG slab produced 46 W of output power with
      315W of pump power. The edge-pumped slab design permits symmetric conduction
      cooling and efficient pump absorption and accepts large-numerical-aperture pump
      sources.

PMID- 18040510
TI  - Waveguide grating mirror for large-area semiconductor lasers.
AB  - We have fabricated and tested a waveguide grating mirror that uses anomalous
      reflection of light associated with excitation of waveguide modes. Sharp features
      are observed in the reflection spectra in both the wavelength and the angular
      domains. We confirm experimentally that, when the waveguide grating mirror is
      placed a short distance in front of a large-area semiconductor laser, it can
      control the emission spectrum. This demonstration opens a new approach to the
      design of very compact semiconductor lasers operating in the single-frequency
      single-mode regime.

PMID- 18040511
TI  - Noninvasive monitoring of glucose concentration with optical coherence
      tomography.
AB  - We have proposed a tested in tissue phantoms and in vivo a novel sensor based on
      optical coherence tomography (OCT) for noninvasive and continuous monitoring of
      blood glucose concentration. OCT images were obtained from pig and rabbit skin
      before and after glucose administration. Slopes of OCT signals decreased
      substantially (~40% in tissues in vivo) and linearly with the increase of blood
      glucose concentration from 4 to 30 mM, typical for normal and diabetic subjects.
      Phantom studies demonstrated 1% accuracy of scattering-coefficient measurement.
      Our theoretical and experimental studies suggest that glucose concentration can
      potentially be measured noninvasively with high sensitivity and accuracy with OCT
      systems.

PMID- 18040512
TI  - Active formation of an antiguide structure in a photorefractive polymer for
      enhanced second-harmonic generation.
AB  - An antiguide structure for enhanced second-harmonic generation was actively
      constructed in a photorefractive polymer by use of a pump beam. Irradiation of a
      pump beam enhanced second-harmonic power, and blocking the pump returned the
      power to the initial value. The electric-field dependence of the degree of
      enhancement of the second-harmonic power confirmed that the antiguide structure
      was constructed through a photorefractive-index change in the medium. The
      photorefractive-index change accompanied molecular reorientation induced by the
      pump-generated space charges. The thermo-optic effect on formation of the
      structure is also discussed.

PMID- 18040513
TI  - Fast photorefractive response in strongly reduced near-stoichiometric LiNbO(3)
      crystals.
AB  - The photorefractive response time of LiNbO(3) crystal is of the order of minutes,
      and such a long response time limits the crystal's practical applications. We
      report the photorefractive properties of nominally pure near-stoichiometric
      LiNbO(3) crystal that is strongly reduced in vacuum. A short photorefractive
      response time of the order of 100 ms is measured at a wavelength of 514.5 nm,
      with incident light intensity of 1.6 W/cm (2) , and possible corresponding
      mechanisms are discussed. To our knowledge this is the first experimental
      evidence of a subsecond photorefractive response in pure LiNbO(3) crystals. The
      diffraction efficiency of a holographic grating written in this reduced crystal
      is low but can be enhanced by an externally applied electric field.

PMID- 18040514
TI  - Polymer-dispersed chiral smectic A with photorefractive properties.
AB  - We present results on the photorefractive properties of chiral smectic A liquid
      crystal phases dispersed in cylindrical cavities in a photoconducting polymer.
      The refractive-index modulation is due to the electroclinic effect, which is
      linear in the electric field, in contrast with the effect that is due to the
      dielectric anisotropy that is typical of nematic phases. We obtained grating
      buildup times of ~25 ms , limited by the speed of the space-charge field
      formation in the photoconducting matrix.

PMID- 18040515
TI  - Soliton algebra by vortex-beam splitting.
AB  - We experimentally demonstrate the possibility of breaking up intense vortex light
      beams into stable and controllable sets of parametric solitons. We report
      observations performed in seeded second-harmonic generation, but the scheme can
      be extended to all parametric processes. The number of generated solitons is
      shown to be determined by a robust arithmetic rule.

PMID- 18040516
TI  - Accurate switching intensities and length scales in quasi-phase-matched
      materials.
AB  - We consider unseeded type I second-harmonic generation in quasi-phase-matched
      quadratic nonlinear materials and derive an accurate analytical expression for
      the evolution of the average intensity. The intensity-dependent nonlinear phase
      mismatch that is due to the cubic nonlinearity induced by quasi phase matching is
      found. The equivalent formula for the intensity of maximum conversion, the
      crossing of which changes the one-period nonlinear phase shift of the fundamental
      abruptly by pi , corrects earlier estimates [Opt. Lett. 23, 506 (1998)] by a
      factor of 5.3. We find the crystal lengths that are necessary to obtain an
      optimal flat phase versus intensity response on either side of this separatrix
      intensity.

PMID- 18040517
TI  - Phase-locked, time-delayed harmonic pulses for high spectral resolution in the
      extreme ultraviolet.
AB  - We present experiments in the time and frequency domains aimed at confirming the
      measured mutual phase coherence of time-delayed, collinear harmonic pulses. We
      show that pairs of phase-locked harmonic pulses of medium order can be generated
      for peak intensities up to ~1.5 10(14)W/cm(2) in xenon, demonstrating the
      possibility of performing high-resolution spectroscopy in the extreme ultraviolet
      with Ramsey-like techniques.

PMID- 18040518
TI  - All-solid-state, tunable, single-frequency source of yellow light for high
      resolution spectroscopy.
AB  - We demonstrate a cw doubly resonant optical parametric oscillator that is
      frequency doubled in an external resonant cavity to the visible spectral range.
      We obtained single-frequency radiation in the range 565-590 nm with as much as
      3.8 mW of power, which is continuously tunable over an 18-GHz range and step
      tunable over 160 GHz. The source is well suited for high-resolution spectroscopy
      in the visible region. As a demonstration, we performed persistent hyperfine
      spectral hole-burning spectroscopy of Eu(3+): Y(2)SiO(5) . Reliable operation of
      the source permitted studies of the hole's lifetime over several hours.

PMID- 18040519
TI  - Large polarization rotation via atomic coherence.
AB  - We report significant enhancement of the nonlinear Faraday rotation in optically
      thick Rb vapor. Polarization rotation angles as large as 10 rad were observed for
      what is believed to be the first time for sub-Gauss magnetic fields. The use of
      this effect for high-precision magnetometry is also discussed.

PMID- 18040521
TI  - Supercontinuum generation and pulse compression in hollow waveguides.
AB  - We present a theoretical study of temporal and spectral characteristics and pulse
      compression in hollow waveguides, using a global approach to dispersion without
      application of the slowly varying envelope approximation. A novel ultrawide self
      phase modulation-induced spectral-broadening regime with spectra covering almost
      3 octaves is predicted for a pressure at which the group-velocity dispersion
      parameter is small and anomalous. Compression to subcycle pulses by an
      appropriate broadband modulator and pulse shortening without chirp control by a
      spectral filter are studied.

PMID- 18040522
TI  - Characterization of arbitrarily polarized ultrashort laser pulses by cross-phase
      modulation.
AB  - We propose a technique for time resolution of the polarization state of
      ultrashort light pulses that also provides the overall time-varying phase of the
      pulse. This method is based on a spectral polarimetric analysis of the pulse
      after propagation through a Kerr medium. The feasibility of this method is
      demonstrated both numerically and experimentally.

PMID- 18040520
TI  - Miniband transmission in a photonic crystal coupled-resonator optical waveguide.
AB  - We demonstrate in the near infrared the coupled-resonator optical waveguide
      (CROW) concept that was recently proposed by Yariv et al. [Opt. Lett.24, 711
      (1999)]. Two-dimensional photonic crystals have been used to define, in a GaAs
      based waveguiding heterostructure, an array of micrometer-sized hexagonal
      cavities coupled through thin walls. With the photoexcitation of InAs quantum
      dots as an internal source, the transmission spectra of the coupled resonators
      show marked minibands and minigaps, in agreement with theoretical predictions.

PMID- 18040523
TI  - The synthesis of C-3beta functionalized indoles via a hydroboration/Suzuki
      Miyaura coupling sequence.
AB  - A method for the functionalization of C-3beta of vinyl indoles is described. The
      procedure involves a hydroboration, followed by a Suxuki-Miyaura cross-coupling
      with the intermediate alkyl borane. Triflates, bromides, and iodides are suitable
      coupling partners, allowing access to a variety of elaborated indole compounds.

PMID- 18040524
TI  - Prevalence of obesity and its associated factors in Aleppo, Syria.
AB  - BACKGROUND:  Obesity and its related adverse health effects have become major
      public health problems in developing countries. It has been increasing more
      rapidly in low-income and transitional than in industrialized countries. This
      study aims to provide the first population-based estimates of the prevalence of
      obesity in Aleppo, Syria, and to examine its association with a number of risk
      factors in the adult population.  METHODS:  An interviewer-administered survey of
      adults 18-65 years of age, residing in Aleppo, Syria was conducted in 2004,
      involving a representative sample of 2038 participants (54.8% female, mean age
      35.3+/-12.1, age range 18-65 years) with a response rate of 86%. Demographic
      factors and anthropometric measurements were obtained for all participants. The
      main outcome was prevalence of obesity which was defined as BMI>= 30 kg/m(2). 
      RESULTS:  The prevalence of obesity was 38.2%, higher in women than in men (46.3%
      and 28.4% respectively). It increased with age being highest in the 46-65 year
      old age group. Obesity was highest among Arabs (40.1%), the unemployed (49.8%),
      illiterate (50.4%), married (44%) especially women with multiparity, low socio
      economic status(45.4%), and those with a low physical activity score (40.3%).
      Obesity was seen among 48.2% of ex-smokers, 39.3% of non-users of alcohol and
      57.5% of participants treated for depression. An association was observed between
      obesity and an increasing frequency intake of certain food items. Among women, an
      association was observed between obesity and the number of births.  CONCLUSION: 
      Our data show that obesity is a major health problem in Aleppo, Syria especially
      among women. It is related to age, marital status, and consumption of certain
      food items and it shows a significant prevalence among women with repeated
      pregnancies.

PMID- 18040526
TI  - Effects of various nonopioid receptor antagonists on the antinociceptive activity
      of Muntingia calabura extracts in mice.
AB  - This study was carried out in mice to determine the nonopioid receptor signaling
      pathway(s) that might modulate the antinociceptive activity of the aqueous and
      chloroform extracts of Muntingia calabura (M. calabura) leaves, using the hot
      plate test. The leaves of M. calabura were sequentially soaked [1:2 (w/v); 72 h]
      in distilled water (dH(2)O) and chloroform. The 50% concentration extracts were
      selected for this study based on the plant's previously established
      antinociceptive profiles. The mice (n = 7) were pretreated (s.c.) for 10 min with
      the selected nonopioid receptor antagonists, followed by the (s.c.)
      administration of the respective extract. The latency of discomfort was recorded
      at the interval time of 0.5, 1, 2, 3, 4 and 5 h after the extract administration.
      The 5 mg/kg atropine, 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg
      pindolol, 1 mg/kg haloperidol and 10 mg/kg bicuculline caused significant (p <
      0.05) reduction in the aqueous extract-induced antinociceptive activity. The 10
      mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol and 10 mg/kg
      bicuculline caused significant (p < 0.05) reduction in the chloroform extract
      induced antinociceptive activity. In conclusion, the central antinociceptive
      activity of M. calabura leaves appears to be involved in the modulation of
      various nonopioid receptor signaling pathways. Its aqueous extract
      antinociceptive activity is mediated via modulation of the muscarinic, alpha(1)
      adrenergic, alpha(2)-adrenergic, beta-adrenergic, dopaminergic and GABAergic
      receptors, while its chloroform extract activity is mediated via modulation of
      the alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic and GABAergic
      receptors.

PMID- 18040525
TI  - A role for MRE11, NBS1, and recombination junctions in replication and stable
      maintenance of EBV episomes.
AB  - Recombination-like structures formed at origins of DNA replication may contribute
      to replication fidelity, sister chromatid cohesion, chromosome segregation, and
      overall genome stability. The Epstein-Barr Virus (EBV) origin of plasmid
      replication (OriP) provides episomal genome stability through a poorly understood
      mechanism. We show here that recombinational repair proteins MRE11 and NBS1 are
      recruited to the Dyad Symmetry (DS) region of OriP in a TRF2- and cell cycle
      dependent manner. Depletion of MRE11 or NBS1 by siRNA inhibits OriP replication
      and destabilized viral episomes. OriP plasmid maintenance was defective in MRE11
      and NBS1 hypomorphic fibroblast cell lines and only integrated, non-episomal
      forms of EBV were detected in a lympoblastoid cell line derived from an NBS1
      mutated individual. Two-dimensional agarose gel analysis of OriP DNA revealed
      that recombination-like structures resembling Holliday-junctions form at OriP in
      mid S phase. MRE11 and NBS1 association with DS coincided with replication fork
      pausing and origin activation, which preceded the formation of recombination
      structures. We propose that NBS1 and MRE11 promote replication-associated
      recombination junctions essential for EBV episomal maintenance and genome
      stability.

PMID- 18040527
TI  - Changes in serum carbonyl and malondialdehyde levels following colchicine and
      vitamin E treatment in Behcet's disease.
AB  - Behcet's disease (BD) is an inflammatory disorder of an unknown cause, but
      growing evidence indicates that the oxidative stress is increased in BD, owing to
      the overproduction of reactive oxygen species (ROS) and decreased efficiency of
      antioxidant defenses. ROS affect proteins and lipids and cause their oxidation,
      therefore, contributing to the formation of oxidation products: carbonyl, a
      marker of protein oxidation, and malondialdehyde (MDA), a marker of lipid
      peroxidation. The investigation was undertaken to evaluate protein oxidation
      (carbonyl group) levels and lipid peroxidation (MDA) levels, and the role of
      colchicine and vitamin E therapy on protein carbonyl group and MDA levels in
      serum samples of patients with BD. In this study, subjects were classified as
      control group, colchicine therapy group alone and colchicine and vitamin E
      therapy group. Protein carbonyl and MDA levels at the beginning of the study were
      significantly (p < 0.05) higher in both therapy groups compared with those of the
      control group. We found that the protein carbonyl and MDA levels at the end of
      the study showed no significant (p > 0.05) differences between the therapy groups
      and control group. These results provide some evidence for a potential effect of
      colchicine and vitamin E therapies on increased protein oxidation and lipid
      peroxidation in BD.

PMID- 18040528
TI  - Absorption and excretion of elderberry (Sambucus nigra L.) anthocyanins in
      healthy humans.
AB  - Pharmacokinetic variables of several dietary anthocyanins (potent natural
      antioxidants) following consumption of elderberry (Sambucus nigra L.) extract
      were evaluated in urine and plasma of six healthy volunteers. They were given a
      single oral dose of either 30 ml (278 mg total anthocyanins) or 200 ml (1852 mg
      total anthocyanins) of a commercially available elderberry extract. Within 7 h,
      the fraction of orally administered total anthocyanins (calculated as the sum of
      cyanidin-3-sambubioside and cyanidin-3-glucoside) excreted unchanged was 0.39%
      and 0.27% following ingestion of 30 and 200 ml, respectively. The elimination
      half-life of total anthocyanins was slightly lower following the consumption of
      278 mg (1.85 h) than that after the consumption of 1852 mg (2.57 h). The renal
      clearance (median) of total anthocyanins was 196 and 169 ml/min, respectively.
      The peak and average systemic exposure to the major elderberry anthocyanidin
      glycosides in plasma as well as their renal excretion exhibited approximate dose
      proportional characteristics within the administered range. The low dose
      normalized area under the concentration-time curve (AUC) and the fraction of
      orally administered anthocyanins recovered unchanged in urine indicate a low
      bioavailability of these compounds.

PMID- 18040530
TI  - Comparison of the effects of unfractionated heparin and the low-molecular-weight
      heparins dalteparin and enoxaparin on spontaneous platelet aggregation and
      adenosine diphosphate activity in platelets during the third trimester of
      pregnancy.
AB  - Low-molecular-weight heparins (LMWHs) have demonstrable pharmacokinetic,
      pharmacodynamic and safety advantages over unfractionated heparin (UH) in routine
      clinical use and are now the preferred agents in routine anticoagulant therapy.
      However, the utility and impact of the LMWH compared with that of UH has not been
      studied extensively in human pregnancy, wherein the prophylaxis against venous
      thromboembolism is imperative. Human pregnancy is a hypercoagulable state with an
      increase in spontaneous platelet aggregation (SPA) in vivo. We evaluated and
      compared the effects of UH and the LMWHs dalteparin and enoxaparin (10 U/ml) on
      SPA in citrated whole blood with an ultraflow platelet counter in pregnancy and
      also investigated the role of adenosine diphosphate (ADP) in heparin-induced
      platelet aggregation in the third trimester of pregnant women (aged 28 +/- 3
      years, gestational age 34 +/- 5 weeks) and in healthy, age-matched nonpregnant
      women. Pregnant women showed a significantly increased SPA of 37% 6 5% compared
      with 16% 6 3% in nonpregnant women (p < 0.01). UH exerted a significantly greater
      proaggregatory effect on SPA compared with that of LMWHs or saline (p < 0.0002;
      ANOVA). The maximum values of SPA were as follows: UH, 69% +/- 5%; dalteparin,
      46% +/- 5%; and enoxaparin, 54% +/- 3%. There was no difference between SPA
      induced by LMWHs and saline or between enoxaparin and dalteparin. At 480 s, there
      was no difference in SPA induced by LMWH between pregnant and nonpregnant women,
      but UH substantially and specifically increased SPA in pregnant women compared
      with that in nonpregnant women (p < 0.01). This heparin-induced platelet
      activation and thrombocytopenic response was reversed by apyrase grade II (ADP
      scavenger) that also inhibited SPA in pregnancy to a level similar to that of
      nonpregnant women (p < 0.0002; ANOVA). These results indicate that the LMWHs
      dalteparin and enoxaparin cause significantly less platelet aggregation in whole
      blood in pregnancy and in the nonpregnant state when compared with UH. The
      proaggregatory platelet effects of UH is substantially enhanced in pregnancy, a
      property not shared by LMWHs. The reversal of the heparin-induced platelet
      activation by apyrase grade II suggests that the mechanism is, at least in part,
      mediated by copious ADP release from platelets or red cells by heparin but not
      LMWHs.

PMID- 18040529
TI  - The effect of tiotropium on the pulmonary diffusing capacity.
AB  - To our knowledge, there is no data on the effect of tiotropium on pulmonary gas
      exchange in healthy subjects. The aim of this study was to assess the effects of
      tiotropium on pulmonary diffusing capacity. Twenty-one healthy volunteers were
      enrolled for a prospective, randomized, double-blind, placebo-controlled study.
      Spirometric measurements, including pulmonary-diffusing capacity, were obtained
      before and after inhalation of drug or placebo. There was a significant decrease
      in forced vital capacity (FVC) and, consequently, an increase in the forced
      expiratory volume in one second (FEV1) to FVC ratio after placebo inhalation (p <
      0.05), but no changes were found for percent-predicted FVC, FEV1, percent
      predicted FEV1, percent-predicted forced expiratory flow (FEF25%-75%), percent
      predicted peak expiratory flow (PEF), diffusing capacity of the lung for carbon
      monoxide (DLCO), single-breath alveolar volume (VA) and DLCO/VA ratio when
      compared with the baseline. Tiotropium inhalation caused a significant increase
      in FVC, percent-predicted FEV1, FEV1/FVC and percent-predicted FEF25%-75%,
      although the decrease in DLCO was insignificant (12.4 +/- 0.9 to 11.4 +/- 0.9).
      In conclusion, tiotropium does not change the pulmonary-diffusing capacity in
      healthy volunteers.

PMID- 18040531
TI  - Gateways to clinical trials.
AB  - (-)-Epigallocatechin gallate, [188Re]-P2045, 12B75, 89-12; Abacavir
      sulfate/lamivudine, Abatacept, Abiraterone acetate, ABT-869, Adalimumab, Ad-rh
      Endostatin, AI-700, Alemtuzumab, Alvimopan hydrate, Amrubicin hydrochloride, AP
      12009, Apomab 7.3, Arformoterol tartrate, Aripiprazole, AS-1404, Azacitidine, AZD
      0530; Bevacizumab, BHT-3009, Biapenem, Bortezomib, Bosentan, Bremelanotide; CA9
      SCAN, Calcitonin gene-related peptide, Canertinib dihydrochloride, Cannabidiol,
      Carboxyamidotriazole, Caspofungin acetate, Celgosivir, Certolizumab pegol,
      Cinacalcet hydrochloride, Clevudine, CP-751871, Curcumin, Cx-401, Cypher;
      Darunavir, Decitabine, Deforolimus, Dexamet, Dipyridamole/prednisolone,
      Drospirenone, Drospirenone/estradiol, DTPw-HepB-Hib, Duloxetine hydrochloride;
      Efalizumab, Emtricitabine, Erlotinib hydrochloride, Escitalopram oxalate,
      Eszopiclone; Ferumoxtran-10, Ferumoxytol, Fondaparinux sodium, Fosaprepitant
      dimeglumine; gamma-Hydroxybutyrate sodium, Gefitinib, Genistein, Ghrelin (human),
      Gimatecan, GM-CSF PMED, Golimumab, gp100 PMED; Imatinib mesylate, Immunoglobulin
      intravenous (human), IV Gamma-globulin; LA-419, Laropiprant, L-BLP-25,
      Levodopa/carbidopa/entacapone, Lidocaine/prilocaine, Lopinavir/ritonavir,
      Lumiracoxib, LY-2076962; Mepolizumab, Methylnaltrexone bromide, Mitiglinide
      calcium hydrate, Mycophenolic acid sodium salt, Myristyl nicotinate; Natalizumab,
      Nesiritide, Niacin/lovastatin; Oblimersen sodium, Ofatumumab, Olmesartan
      medoxomil, Olmesartan medoxomil/hydrochlorothiazide, Ozarelix; Palonosetron
      hydrochloride, Parathyroid hormone (human recombinant), Pazopanib hydrochloride,
      Pegaptanib octasodium, Pegfilgrastim, Peginterferon alfa- 2a, Peginterferon alfa
      2b, Pegvisomant, Pemetrexed disodium, Pexelizumab, Picoplatin, Pimecrolimus,
      Posaconazole, Pregabalin, PRO-1762, Progesterone caproate, Prulifloxacin;
      Ramelteon, Ranelic acid distrontium salt, Reparixin, Rosuvastatin calcium;
      Rotigotine; Satraplatin, Sertraline, Sipuleucel-T, SLIT-cisplatin, SNDX-275,
      Solifenacin succinate, Sunitinib malate; Tadalafil, Talnetant, Tanespimycin,
      Taxus, Tegaserod maleate, Telmisartan/hydrochlorothiazide, Tenofovir disoproxil
      fumarate/emtricitabine, Teriparatide, tgAAC-94, Tiotropium bromide, Tocilizumab,
      Tolvaptan, Trimethoprim; Vardenafil hydrochloride hydrate, Vatalanib succinate,
      Vinflunine, Voriconazole, VX-680; XL-880; Yttrium 90 (90Y) ibritumomab tiuxetan.

PMID- 18040532
TI  - Experiences of orphan care in Amach, Uganda: assessing policy implications.
AB  - Uganda is estimated to have around two million orphans constituting approximately
      19% of all the children in the country. This paper presents findings from a study
      on the experiences of orphan care among Langi people of Amach sub-county in Lira
      District, northern Uganda, and discusses their policy implications. The study
      utilised the following methods in data collection: eight months of ethnographic
      fieldwork; 21 in-depth interviews with community leaders; 45 with heads of
      households caring for orphans; 35 with orphans; and five focus group discussions.
      The findings revealed that the Langi people have an inherently problematic orphan
      concept, which contribute toward discriminatory attitudes and practices against
      orphans. The clan based decision-making to care for orphans, the category of kin
      a particular orphan ends up living with, the sex and age of the orphan, as well
      as the cessation of the 'widow-inheritance' custom emerged as prominent factors
      which impact on orphan care. Thus there is the need to draw upon such local
      knowledge in policy making and intervention planning for orphans. The paper
      concludes with a discussion of potential approaches to alleviating the current
      orphan challenges among the Langi people.

PMID- 18040534
TI  - HIV/AIDS through the lens of Christianity: perspectives from a South African
      urban support group.
AB  - HIV is one of the most obscure viruses that humankind has had to face in recent
      times. Compounding this obscurity are often contesting perspectives on what it
      means to be HIV infected, and these perspectives are largely constituted by
      people's rationalisation of complex situations or experiences. Using qualitative
      research methods and ethnography in particular, this paper reflects on a broad
      understanding of what it means to live with HIV in the context of Christianity,
      using research participants' perspectives in an urban support group setting. Two
      fundamental patterns are evident in this paper: (1) as support group members
      rationalise their HIV infection, they continuously construct and reconstruct
      their identities; and (2) support group members rationalise their HIV infection
      to enhance their coping abilities, using Christianity and the Bible in
      particular, as a reference. Whilst rationalising HIV infection, three viewpoints
      emerge. The first viewpoint perceives HIV infection as an affliction by Satan;
      the second viewpoint sees it as originating from God; while the last viewpoint
      interprets HIV infection as a negotiated settlement between God and Satan. The
      paper is intended to trigger debate, and hopefully also to seek and provide
      answers from various sectors of society, and religious communities in particular,
      in order to help other HIV positive people in similar situations better manage
      their HIV condition.

PMID- 18040535
TI  - Equity in access to ARV drugs in Malawi.
AB  - This paper discusses the issue of equity in the distribution of ARV drugs in the
      Malawi health system. Malawi is one of the countries most severely affected by
      HIV/AIDS in southern Africa. It is also one of the poorest countries in the
      world. ARV drugs are expensive.The Malawi government, with assistance from the
      Global Fund on Tuberculosis, Malaria and HIV/AIDS, started providing free ARV
      drugs to eligible HIV-infected people in September 2004. The provision of free
      drugs brought the hope that everyone who was eligible would access them. Based on
      data collected through a qualitative research methodology, it was found that
      achieving equity in provision would face several challenges including policy,
      operational and socio-economic considerations. Specifically, the existing policy
      framework, shortage of medical personnel, access to information and inadequacy of
      effective community support groups are some of the key issues affecting equity.

PMID- 18040533
TI  - Difficult choices: infant feeding experiences of HIV-positive mothers in northern
      Tanzania.
AB  - Infant feeding represents a great challenge in the prevention of mother-to-child
      transmission of HIV (pMTCT). The international guidelines informing infant
      feeding counselling suggest feeding methods that reduce the risk of HIV
      transmission, and discourage mixed feeding (combining breastfeeding with other
      fluids and solids). The feasibility and the social acceptability of the
      recommended feeding methods are hotly debated currently. Through the
      documentation of HIV-positive women's experiences, this article aims to provide
      empirically grounded knowledge on the relevance of the proposed feeding methods.
      Drawing upon cultural theory and a view of infant feeding practices as socially
      and culturally embedded, the article discusses the so-called 'informed choice' of
      infant feeding method among women enrolled in the pMTCT programme at Kilimanjaro
      Christian Medical Centre in northern Tanzania.The study is based on interviews
      and follow-up of 20 HIV-positive mothers during the last part of pregnancy,
      delivery and the first six months after birth. The article details four of these
      cases describing the challenges linked to exclusive breastfeeding, cow's milk
      feeding and formula feeding. The study demonstrates the gap between intentions
      and infant feeding practice in a context where the social expectations to
      breastfeed are high, and where kin and neighbours are part of the decision-making
      team surrounding infant feeding. It highlights the tension between the competing
      concerns of the medical and social risks involved in the choice of infant feeding
      method, and documents that the feeding options may be difficult to adhere to,
      whether a mother chooses exclusive breastfeeding or replacement feeding.

PMID- 18040537
TI  - The future of the multidisciplinary clinic.
AB  - The multidisciplinary clinic is the accepted model for health care delivery
      related to spina bifida. This article focuses on the factors affecting
      multidisciplinary care delivery and future challenges for multidisciplinary
      programs.

PMID- 18040536
TI  - Met and unmet palliative care needs of people living with HIV/AIDS in Rwanda.
AB  - The rising number of people living with HIV/AIDS (PLWHA) worldwide has made
      health care professionals and policy makers search for accessible health care
      that will meet the needs of people who are suffering from the disease and enhance
      their quality of life (QoL). This study investigated met and unmet palliative
      care needs of PLWHA in selected areas in Rwanda. The study sample included 306
      participants: PLWHA, health care professionals and coordinators of HIV/AIDS
      units. Quantitative and qualitative methodologies were used. The data were
      analysed separately and then triangulated. In the findings, over 50% of PLWHA had
      symptoms related to HIV/AIDS most of the time, with the most common symptom being
      pain. Participation in activities of daily living was significantly associated
      with the health status of PLWHA (p<0.001). The most common perceived palliative
      care needs of PLWHA were medical needs, psychosocial needs and the need for
      financial assistance (77%); home-based care (47%); nutritional support (44%); and
      pain relief and management of other symptoms (43%). Most PLWHA indicated these
      palliative care needs were unmet, in particular the need for pain relief, symptom
      management, financial assistance and nutritional support. Over 50% of health care
      professionals reported they were not trained in palliative care. They indicated
      that inadequate policy and resources were the main obstacles to the provision of
      optimal palliative care. Addressing unmet palliative care needs would enhance the
      QoL of PLWHA. In addition, developing policy related to the provision of
      palliative care and building the capacity of health care providers is essential
      for the provision of adequate palliative care services in Rwanda.

PMID- 18040538
TI  - Increased apoptosis and proliferative capacity are early events in cyst formation
      in autosomal-dominant, polycystic kidney disease.
AB  - Previous studies have highlighted epithelial proliferation and apoptosis in the
      cyst lining as common features in animal models of cystic disease. In this study,
      we sought to evaluate the timing and extent of these changes in renal tissue
      obtained from patients with autosomal-dominant, polycystic kidney disease (ADPKD)
      subjected for nephrectomy for a variety of clinical indications. Cell
      proliferation was assessed using an antibody to proliferating cell nuclear
      antigen (PCNA), and apoptosis was evaluated by the use of terminal
      deoxynucleotidyl transferase (TdT) digoxigenin-deoxyuridine (dUTP) nick end
      labeling technique (ApopTag(R)). The origin of cystic structures was evaluated
      using antibodies to epithelial membrane antigen (EMA). The lineage of
      interstitial mononuclear cells was assessed by anti CD 45 and CD 68 monoclonal
      antibodies. We found an increased rate of proliferation within the epithelium,
      not only of cystic, but also of noncystic, tubules that was significantly higher
      than the corresponding values from normal kidney (p pound 0.0001). Apoptotic
      index values were significantly increased within the epithelium lining noncystic
      and cystic structures (p < 0.001). In the interstitium, increased proliferation
      and apoptosis rates were also noted. Interstitial infiltrates were dense and
      consisted mainly of CD 68-positive macrophages and CD 45-positive lymphocytes.
      The present study demonstrated that changes in cell turnover are early events in
      cyst formation. The observation of mild proportionate elevation of both
      proliferation and apoptosis values of the epithelium lining cysts explains the
      lack of increase risk of renal cell carcinoma in ADPKD. The development of heavy
      interstitial inflammation could contribute to progressive tubulointerstitial
      scarring, leading to progressive renal failure.

PMID- 18040539
TI  - Traumatic brain injury and delayed sequelae: a review--traumatic brain injury and
      mild traumatic brain injury (concussion) are precursors to later-onset brain
      disorders, including early-onset dementia.
AB  - Brain injuries are too common. Most people are unaware of the incidence of and
      horrendous consequences of traumatic brain injury (TBI) and mild traumatic brain
      injury (MTBI). Research and the advent of sophisticated imaging have led to
      progression in the understanding of brain pathophysiology following TBI. Seminal
      evidence from animal and human experiments demonstrate links between TBI and the
      subsequent onset of premature, psychiatric syndromes and neurodegenerative
      diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD).
      Objectives of this summary are, therefore, to instill appreciation regarding the
      importance of brain injury prevention, diagnosis, and treatment, and to increase
      awareness regarding the long-term delayed consequences following TBI.

PMID- 18040540
TI  - Origin, fate, and function of epicardium-derived cells (EPDCs) in normal and
      abnormal cardiac development.
AB  - During heart development, cells of the primary and secondary heart field give
      rise to the myocardial component of the heart. The neural crest and epicardium
      provide the heart with a considerable amount of nonmyocardial cells that are
      indispensable for correct heart development. During the past 2 decades, the
      importance of epicardium-derived cells (EPDCs) in heart formation became
      increasingly clear. The epicardium is embryologically formed by the outgrowth of
      proepicardial cells over the naked heart tube. Following epithelial-mesenchymal
      transformation, EPDCs form the subepicardial mesenchyme and subsequently migrate
      into the myocardium, and differentiate into smooth muscle cells and fibroblasts.
      They contribute to the media of the coronary arteries, to the atrioventricular
      valves, and the fibrous heart skeleton. Furthermore, they are important for the
      myocardial architecture of the ventricular walls and for the induction of
      Purkinje fiber formation. Whereas the exact signaling cascades in EPDC migration
      and function still need to be elucidated, recent research has revealed several
      factors that are involved in EPDC migration and specialization, and in the cross
      talk between EPDCs and other cells during heart development. Among these factors
      are the Ets transcription factors Ets-1 and Ets-2. New data obtained with
      lentiviral antisense constructs targeting Ets-1 and Ets-2 specifically in the
      epicardium indicate that both factors are independently involved in the migratory
      behavior of EPDCs. Ets-2 seems to be especially important for the migration of
      EPDCs into the myocardial wall, and to subendocardial positions in the
      atrioventricular cushions and the trabeculae. With respect to the clinical
      importance of correct EPDC development, the relation with coronary arteriogenesis
      has been noted well before. In this review, we also propose a role for EPDCs in
      cardiac looping, and emphasize their contribution to the development of the
      valves and myocardial architecture. Lastly, we focus on the congenital heart
      anomalies that might be caused primarily by an epicardial developmental defect.

PMID- 18040541
TI  - The child with a disability: parental acceptance, management and coping.
AB  - Research indicates that family reaction to the birth of a disabled child changes
      according to the type of disability and the child's diagnostic category. The
      differences are probably an indirect consequence of anticipated or actual
      reactions by those surrounding the disabled child and the family, in addition to
      parental reactions. Many researchers have recently mentioned the positive coping
      and functioning of many families with developmentally disabled children. In the
      past there was a tendency to emphasize issues of illness and pressures, spousal
      strain and maladjustment within the family, while presently they are replaced
      with questions concerning positive adjustment, satisfaction, acceptance, and
      spousal harmony. Rather than perceiving the family as a helpless victim, it is
      perceived as a unit that adapts by a process of structuring. Professionals must
      acknowledge the importance of the family, this change towards a positive attitude
      towards disability and that the controls decisions concerning the disabled child
      and the family.

PMID- 18040542
TI  - First do no harm: an analysis of the risk aspects and side effects of clinical
      holistic medicine compared with standard psychiatric biomedical treatment.
AB  - Clinical holistic medicine (CHM) is short-term psychodynamic psychotherapy (STPP)
      complemented with bodywork and philosophical exercises, to be more efficient in
      treating patients with severe mental and physical illness. STPP has already been
      found superior to psychiatric treatment as usual (TAU) and thus able to compete
      with psychiatric standard treatment as the treatment of choice for all non
      organic mental illnesses; we have found the addition of bodywork and philosophy
      of life to STPP to accelerate the process of existential healing and recovery
      (salutogenesis). In this paper we compare the side effects, suicidal risk,
      problems from implanted memory and implanted philosophy of CHM with
      psychopharmacological treatment. METHOD: Qualitative and quantitative comparative
      review. RESULTS: In all aspects of risks, harmfulness, and side effects, we have
      been considering, CHM was superior to the standard psychiatric treatment. The old
      principle of "first do no harm" is well respected by CHM, but not always by
      standard psychiatry. CHM seems to be able to heal the patient, while
      psychopharmacological drugs can turn the patient into a chronic, mentally ill
      patient for life. Based on the available data CHM seems another alternative to
      patients with mental illness. There seem to be no documentation at all for CHM
      being dangerous, harmful, having side effects of putting patients at risk for
      suicide. As CHM uses spontaneous regression there is no danger for the patient
      developing psychosis as, according to some experts, has been seen with earlier
      intensive psychodynamic methods. CHM is an efficient, safe and affordable cure
      for a broad range of mental illnesses.

PMID- 18040543
TI  - A review and integrative analysis of ancient holistic character medicine systems.
AB  - The ancient holistic medical systems help the patient by balancing the "elements"
      of the human character. This work aims to understand the nature of these elements
      and the process of the physician balancing them. Using the concept of poly-ray
      cosmology we see that the medical systems from ancient India, China and Greek
      basically share the same inner structure and also the same logic of the treatment
      processes. We analyze the double concept of yin-yang, the Ayurvedic triadic
      concepts of Pitta, Kapha and Vata, the four elements of Hippocratic humoral
      medicine, and the five elements of Chinese medicine, and find that each of these
      conceptual frameworks make up a "theory" or model of the world that is a perfect
      wholeness, allowing the physician to interpret the world and his patient in order
      to identify the imbalances of his or her character that need to be treated.
      Independently of the system this can be a palliative treatment, if energies are
      only balanced in present time, or a causal cure if the physician is using the
      similarity principle to take his patient into regression back to the events in
      the personal history that originally created the imbalances (the traumas). To
      help the patient back to the traumas he is exposed to a small dose of the
      original harming stimulus; this can be an internal process like visualization
      supported by the therapist words, or an external process provoked by his actions.
      If the physician is balancing the elements without such a healing of the
      patient's existential core this can still momentarily help the patient by
      alleviating the symptoms, but it will not have a permanent effect.

PMID- 18040544
TI  - Heparan sulfate proteoglycan-involving immunomodulation by cathelicidin
      antimicrobial peptides LL-37 and PR-39.

PMID- 18040547
TI  - [Abstracts of the XXIII Congress of Pulmonology, 8-10 November 2007, Guarda,
      Portugal].

PMID- 18040545
TI  - Fournier's gangrene--findings on computed tomography.

PMID- 18040546
TI  - Pediatric burns in the Bedouin population in southern Israel.
AB  - Burn trauma is an important public health concern, with increased risk for burns
      in children. A cross-sectional study was performed to describe the
      epidemiological characteristics and risk factors for burns in hospitalized
      Bedouin children in Soroka University Medical Center during the years 2001-2002.
      In a population of 558 hospitalized burn-injured patients, 282 Bedouin children
      were identified. Two hundred and sixty five patients (94.0%) had burns involving
      less than 20% of the body surface area. Cause of the burns was scald in 190
      patients (67.4%), fire in 80 patients (28.4%), chemical in 8 patients (2.8%), and
      explosion in 2 patients (0.7%). Two female patients (0.7%) aged 11 and 17 years
      died of their burns that were caused by fire. The mean length of hospitalization
      was 9.8 days. Pediatric burn injury has become a significant public health
      problem in the Bedouin population of the Negev. To reduce the burden of burn
      injury, it is necessary to increase current efforts in prevention of burns.

PMID- 18040589
TI  - The prevalence of DSM-IV psychiatric disorders among 7-10 year old Yemeni
      schoolchildren.
AB  - BACKGROUND: The planning of child mental health services should be based on
      recent high-quality data on the prevalence and type of mental health disorders,
      and yet such data are not available in Yemen and many other Arab countries.
      METHODS: Representative samples of Yemeni 7-10 year olds (n = 1,210) were
      assessed using a two-phase design in an urban area and a one-phase design in a
      rural area. Psychopathology was assessed using the Strengths and Difficulties
      Questionnaire for screening purposes and the Development and Well-being
      Assessment to generate psychiatric diagnoses. RESULTS: The overall prevalence of
      DSM-IV disorders was 15.7% in Yemen (95% CI 11.7-20.2%). Anxiety disorders were
      the commonest diagnostic grouping in Yemen (9.3%, 95% CI = 5.8-12.8%), followed
      by behavioural disorders (7.1%, 95% CI = 4.4-9.9%) and attention
      deficit/hyperactivity disorder (ADHD; 1.3%, 95% CI = 0.1-2.5%). There were no
      significant urban-rural differences. CONCLUSIONS: Roughly a sixth of Yemeni
      schoolchildren have at least one DSM-IV psychiatric disorder, involving a level
      of distress or social impairment likely to warrant treatment.

PMID- 18040590
TI  - Factors associated with use of psychotherapy.
AB  - CONTEXT: Psychotherapies are recommended in manuals of good practice. There is
      however little epidemiological data assessing access to this type of treatment,
      and in particular the combined role of the offer and socio-demographic
      characteristics. The present research aims to contribute data on the profiles of
      a sample of individuals who underwent psychotherapy in France, and on the
      respective impact of various factors such as mental health status, socio
      demographic characteristics, life events and the care offer, focusing on a
      specific population for whom the mode of financial cover for this type of care is
      governed by a complementary health insurance (MGEN). METHODS: Between June 1999
      and March 2000 a survey using a self-administered questionnaire was conducted on
      a sample of MGEN-insured individuals. Ten thousand individuals aged between 20
      and 60 were selected randomly, received a questionnaire, and up to three recalls
      in case of non-response. The overall response rate was 66.5%. The questionnaire
      comprised 261 questions enabling data collection concerning the main socio
      demographic, professional and mental health variables. RESULTS: In this
      population aged from 20 to 60, lifetime prevalence of recourse to psychotherapy
      was 11.8%. The main factor associated with use of psychotherapy is the severity
      of the clinical condition (assessed in terms of comorbidity). Certain traumatic
      events experienced in childhood are also related. The effect of socio-demographic
      variables varies according to severity, although it was noted that being female,
      having high educational status, and being single were consistently related to
      wider use of psychotherapy. The analysis also evidenced the importance of the
      density of the care offer. CONCLUSION: Our results suggest that the use of
      psychotherapy, within a well-informed population with high quality insurance
      cover, is related primarily to clinical condition rather than to socio
      demographic status, especially in people with high levels of comorbidity,
      although the effect of educational status remains. However, this study only
      looked at mere use of psychotherapy, without determining the suitability of the
      treatment provided. It is indeed possible, and even probable, that variables such
      as educational status, income, or care offer may have a link with resorting to
      the right type of care, in terms of both relevance and adequate duration.

PMID- 18040591
TI  - Plastid isoprenoid metabolism in the oyster parasite Perkinsus marinus connects
      dinoflagellates and malaria pathogens--new impetus for studying alveolates.

PMID- 18040593
TI  - Temporal trends and spatial variability of mercury in four fish species in the
      Ontario segment of the St. Lawrence River, Canada.
AB  - The Massena (New York) and Cornwall (Ontario) region has a long history of Hg
      discharge into the St. Lawrence River. The objectives of this study were to
      evaluate if Hg levels have declined in this portion of the river since 1975 and
      to compare Hg level in fish species upstream and downstream of this area in order
      to evaluate the anthropogenic contribution to Hg levels in fish. Mercury levels
      in four fish species were monitored over a 20-year period (1975-1995). A general
      linear model and an analysis of covariance were used to extract temporal trends
      and spatial variability, respectively, while correcting the data for fish length.
      Over time, Hg levels declined in most fish species. In the four regions studied,
      Hg levels in fish were similar, which suggests that other sources like
      atmospheric deposition and Hg loading from the Great Lakes may also contribute to
      the Hg burden in fish in the St. Lawrence River. This indicates that fish, with
      large home range, are good biomonitors of temporal Hg releases but their ability
      to avoid point sources makes them less appealing as biomonitors to address
      spatial variability in Hg releases.

PMID- 18040592
TI  - Cadmium chloride-induced disruption of testicular steroidogenesis in rainbow
      trout, Oncorhynchus mykiss.
AB  - Cadmium (Cd) is a known endocrine disruptor with the ability to affect the
      production of hormones involved in the regulation of reproductive processes. In
      the present study, the effects of CdCl(2) on unstimulated and stimulated
      testicular steroidogenesis were examined with the intention of furthering the
      understanding of the potential site(s) of action in the signaling pathway for 11
      KT synthesis in teleosts. In short-term (2-h) exposures, CdCl(2 )stimulated 11-KT
      production (29% and 28% over controls) in minced testicular tissues at
      concentrations of 10 and 100 microM, respectively. However, 11-KT production was
      significantly lower than in controls (54%, 62%, and 54%) when tissues were
      incubated for 18 h with 1, 10, and 100 microM Cd. Incubation of testicular
      tissues with 100 IU/ml human chorionic gonadotropin (hCG) and 5 mM dibutyryl-cAMP
      (dbcAMP), which activate rate-limiting steps in steroid synthesis, or 1.3 microM
      25-hydroxycholesterol (25-OHC), which augments production, resulted in
      significant increases in steroidogenesis over controls. hCG-stimulated
      steroidogenesis was reduced to 54% and 62% that of stimulated controls when
      tissues were incubated with CdCl(2) at 1 and 10 microM, respectively. 11-KT
      production in dbcAMP-stimulated and 25-OHC-augmented tissues was not affected by
      Cd exposure. The results of this study indicate that one site of action of Cd in
      the signaling steroidogenic pathway is located prior to cAMP formation. This
      impairment could be overcome when higher concentrations of Cd were used in hCG
      stimulated cells, suggesting the presence of a stimulatory site at, or following,
      hCG receptor binding.

PMID- 18040594
TI  - Arterial anatomy of the lateral orbital and cheek region and arterial supply to
      the "peri-zygomatic perforator arteries" flap.
AB  - Arterial anatomy of the lateral orbital and cheek region and subsequently of the
      "peri-zygomatic perforator arteries" flap is described, based upon the dissection
      of the 24 human cadaver head halves. Each specimen was dissected in subdermal,
      first fascial and deep level. The subdermal vascular network of lateral orbital
      and cheek region, its orientation and contributing arteries were studied. Origin,
      perforation sites and diameters of transverse facial, zygomaticoorbital,
      zygomaticofacial and zygomaticotemporal arteries were also described and
      measured. Our findings support the view that the cheek island flap used for lower
      eyelid is a reverse flow axial pattern flap. It includes arterioles of the
      transverse facial artery, which are part of the subdermal vascular plexus and are
      uniformly longitudinally oriented. The flap receives its blood supply via
      perforators of the zygomaticoorbital, zygomaticofacial and zygomaticotemporal
      arteries, which are connected via their terminal branches with transverse facial
      artery.

PMID- 18040595
TI  - Parity mediates the association between infant feeding method and maternal
      depressive symptoms in the postpartum.
AB  - Maternal depression is the most common complication of the postpartum, having
      devastating and long lasting effects on mother and infant. Lactation is
      associated with attenuated stress responses, especially that of cortisol, and the
      lactogenic hormones, oxytocin and prolactin, are associated with anti-depressant
      and anxiolytic effects. These associations suggest that breast-feeding may
      decrease maternal depressive symptoms, yet empirical results have been
      conflicting. Recent findings have indicated that parity may mediate the
      association between breast-feeding and stress response. Because a decreased
      stress response is associated with a decreased risk for depression, parity may
      also mediate the association between infant feeding method and depressive
      symptoms. Specifically, the benefits of breast-feeding may appear in multiparous
      but not primiparous mothers. In the present study, data drawn from a national
      sample of primiparous and multiparous mothers were examined for possible
      associations between infant feeding method and depressive symptoms, as assessed
      by the Center for Epidemiological Survey-Depression scale (CES-D). After
      controlling for several possible confounding variables, breast-feeding by
      multiparas was associated with significantly decreased odds of having depression
      compared with bottle-feeders (OR = 0.41, CI 0.19-0.87, p = 0.02); however, no
      risk reduction from breast-feeding was evident among primiparas. The results
      support a parity-mediated association between lactation and maternal depressive
      symptoms. The results provide a reason for earlier conflicting findings, present
      new research avenues, and suggest possible clinical approaches.

PMID- 18040596
TI  - Postpartum depression in adolescents in Brazil: an issue of concern.

PMID- 18040597
TI  - The present importance of the organic psychoses of pregnancy, parturition and the
      puerperium.

PMID- 18040598
TI  - The relationship between personality traits and eating pathology in adolescent
      girls.
AB  - This research investigated the relationship between personality and the tendency
      towards developing eating disorders in adolescent females Personality traits were
      assessed using the High School Personality Questionnaire (HSPQ) and dysfunctional
      eating attitudes and behaviours were assessed using the Eating Attitudes Test
      (EAT-26) and the Eating Disorder Inventory (EDI). The sample consisted of 244
      students from a high school in Johannesburg, South Africa. Significant
      relationships were found between certain personality traits and eating
      dysfunction. Reservation, emotional instability, excitability, opportunism,
      shyness, individualism, proneness to guilt feelings, self-sufficiency and high
      tension were the personality factors that were significant in relation to eating
      dysfunction. This thus suggests that personality appears to influence the
      tendency towards developing eating disorders.

PMID- 18040600
TI  - Abstracts from a joint meeting of the Faculty of Paediatrics of the Royal College
      of Physicians of Ireland and the Irish Paediatric Association. May 17-18, 2007.
      Limerick, Ireland.

PMID- 18040599
TI  - Reliability and validity of the Italian version of the hand functional disability
      scale in patients with systemic sclerosis.
AB  - The English version of hand functional disability scale is a validated instrument
      for measuring hand involvement in patients with systemic sclerosis (SSc). Because
      validation of multiple-language versions of existing validated questionnaires
      plays a key role in standardizing the outcome measurement and increasing the
      statistical power of clinical studies, this study aims to validate a translated
      Italian version of hand functional disability scale which is not available at the
      moment. The Italian version of hand functional disability scale was tested on 50
      patients with SSc. To determine test-retest reliability, 40 SSc patients were
      asked to complete the questionnaire a second time within 2 weeks of the initial
      testing session. The test-retest reliability and internal consistency were
      determined by intra-class correlation coefficient (ICC) and Cronbach's alpha.
      External consistency was measured by comparing with an already validated test,
      the Health Assessment Questionnaire (HAQ), and clinical measurements. To explore
      the relationships among these variables, multiple correspondence analysis (MCA)
      was adopted. The statistical analysis of each domain and the total score revealed
      a good test-retest reliability (ICCs > 0.75) and internal consistency (Cronbach's
      alpha > 0.7). Furthermore, a good external consistency was confirmed by
      evaluating the differences between the distributions of hand functional
      disability scale score for SSc patients with or without hand involvement
      (arthralgias, arthritis, flexion contractures, and digital ulcers) and comparing
      results with those obtained for HAQ. Finally, MCA demonstrates a strong
      correlation among functional disability scale areas and HAQ scores. The hand
      functional disability scale is a self-administered questionnaire and it has been
      specially developed to measure hand impairment in patients with hand disorders.
      Our data support its validity and reliability in Italian SSc patients.

PMID- 18040601
TI  - Rapid tumor doubling in the CNS.

PMID- 18040602
TI  - Biological characterization of Sorona polymer from corn-derived 1,3-propanediol.
AB  - The Sorona family of polymers, based on corn-derived 1,3-propanediol, have
      recently been developed as novel bio-based materials for use in plastics, films,
      and fibers. In the present study, Sorona polymers were investigated for their
      effects on cell survival and inflammatory cell activation using in vitro mouse
      cell cultures. Cytotoxicity of Sorona polymers was evaluated by placing material
      samples in direct contact with 3T3 fibroblast cells. Both Sorona plastic and
      Sorona films were non-cytotoxic to fibroblasts. The inflammatory potential of
      Sorona samples was evaluated by exposing J774 macrophage cells to material
      samples, and measuring TNF-alpha release from macrophages. Sorona plastic and
      Sorona films did not elicit inflammatory TNF-alpha release from macrophages.
      These results indicate that Sorona polymers are non-cytotoxic and non
      inflammatory. While the 1,3-propanediol component of Sorona 3GT is manufactured
      in a bacterial fermentation process, the absence of an inflammatory response to
      Sorona film and Sorona plastic is highly encouraging. The results are significant
      for the design of materials that utilize bio-based polymers.

PMID- 18040604
TI  - Application of Taguchi's method in the optimization of bridging efficiency
      between confluent and fresh microcarriers in bead-to-bead transfer of Vero cells.
AB  - Taguchi's L8 experimental design was firstly applied to identify critical
      parameters affecting the efficiency of bridge formation between confluent and
      fresh microcarriers in bead-to-bead transfer of Vero cells. Statistical analysis
      indicated that stirring time, rest time and the interactions between stirring
      time and rest time, stirring speed and rest time had significant effects.
      Subsequently, a two-stage cell transfer process was performed successfully, in
      which an efficiency of bridge formation (15.3 +/- 1.7%) obtained from 8 h
      intermittent agitation made percentage of bare microcarriers decrease quickly
      from 66.7% to 2.0 +/- 0.8%.

PMID- 18040605
TI  - Vanillin production using Escherichia coli cells over-expressing isoeugenol
      monooxygenase of Pseudomonas putida.
AB  - The isoeugenol monooxygenase gene of Pseudomonas putida IE27 was inserted into an
      expression vector, pET21a, under the control of the T7 promoter. The recombinant
      plasmid was introduced into Escherichia coli BL21(DE3) cells, containing no
      vanillin-degrading activity. The transformed E. coli BL21(DE3) cells produced
      28.3 g vanillin/l from 230 mM isoeugenol, with a molar conversion yield of 81% at
      20 degrees C after 6 h. In the reaction system, no accumulation of undesired by
      products, such as vanillic acid or acetaldehyde, was observed.

PMID- 18040603
TI  - Inhibitory effects of arbutin-beta-glycosides synthesized from enzymatic
      transglycosylation for melanogenesis.
AB  - To develop a new skin whitening agent, arbutin-beta-glycosides were synthesized
      and evaluated for their melanogenesis inhibitory activities. Three active
      compounds were synthesized via the transglycosylation reaction of Thermotoga
      neapolitana beta-glucosidase and purified by recycling preparative HPLC. As
      compared with arbutin (IC(50 )= 6 mM), the IC(50 )values of these compounds were
      8, 10, and 5 mM for beta-D -glucopyranosyl-(1-->6)-arbutin, beta-D: 
      glucopyranosyl-(1-->4)-arbutin, and beta-D -glucopyranosyl-(1-->3)-arbutin,
      respectively. beta-D: -Glucosyl-(1-->3)-arbutin also exerted the most profound
      inhibitory effects on melanin synthesis in B16F10 melanoma cells. Melanin
      synthesis was inhibited to a significant degree at 5 mM, at which concentration
      the melanin content was reduced to below 70% of that observed in the untreated
      cells. Consequently, beta-D: -glucopyranosyl-(1-->3)-arbutin is a more effective
      depigmentation agent and is also less cytotoxic than the known melanogenesis
      inhibitor, arbutin.

PMID- 18040606
TI  - Microcalorimetric studies of the biological effect of holmium (III) on
      Halobacterium halobium R1 growth.
AB  - The biological effect of Ho3+ on Halobacterium halobium R1 growth was analyzed by
      a microcalorimetric technique. By means of LKB-2277 Bioactivity Monitor, ampoule
      method at 37 degrees C, we obtained the thermogenic curves of H. halobium R1
      growth. To analyze the results, the maximum power (Pm) and the growth rate
      constants (k) were determined, which show that values of Pm and k are linked to
      the concentration of Ho3+. In all, the addition of Ho3+ causes a decrease of the
      maximum heat production and growth rate constants. For comparison, we observed
      the shapes of H. halobium R1 cell by means of transmission electron microscope
      (TEM). According to the thermogenic curves and TEM photos of H. halobium R1 under
      different conditions, it is clear that metabolic mechanism of H. halobium R1
      growth has been changed with the addition of Ho3+.

PMID- 18040607
TI  - Changing management in patients with papillary thyroid cancer.
AB  - The incidence of thyroid cancer has been increasing over the past 30 years, and
      it is now the seventh most common cancer in women. Papillary thyroid cancer is
      the most common subtype of thyroid cancer, occurring in 80% of cases. Its main
      pattern of spread is to cervical lymph nodes, with distant metastases occurring
      uncommonly. Initial treatment of papillary thyroid cancer involves resection of
      the primary tumor, with resection of regional lymph nodes if involved with
      metastatic disease. Postoperative adjuvant therapy consists of radioactive iodine
      ablation for most patients, followed by thyroid-stimulating hormone (TSH)
      suppression with thyroxine. An ongoing controversy in the surgical treatment of
      papillary thyroid cancer is that of extent of thyroid gland and nodal resection.
      Consensus guidelines recommend total or near-total thyroidectomy, rather than
      thyroid lobectomy, as the initial procedure of choice, given its advantages of
      treating potential multicentric disease, facilitating maximal uptake of adjuvant
      radioactive iodine, and facilitating the post-treatment follow-up by monitoring
      serum thyroglobulin (Tg) levels. In the hands of an experienced endocrine
      surgeon, complication rates are comparable to those for lobectomy. Major changes
      in the management of patients with papillary thyroid cancer over the last 10
      years include the use of preoperative neck ultrasound, which can detect
      nonpalpable cervical lymph node metastases and potentially change the initial
      operation. In addition, neck ultrasound and measurement of serum Tg levels have
      taken the place of routine whole body radioactive iodine scans in the
      postoperative follow-up of patients with papillary thyroid cancer. Recurrent
      locoregional cervical lymph node disease should be treated by compartmental lymph
      node dissection, followed by another treatment dose of radioactive iodine.
      Chemotherapy is generally ineffective for the treatment of metastatic disease.
      For those patients whose tumor has become radioactive iodine resistant, emerging
      therapies include redifferentiation agents, antiangiogenic agents, and multi
      tyrosine kinase inhibitors.

PMID- 18040608
TI  - Increased radiosensitivity as an indicator of genes conferring breast cancer
      susceptibility.
AB  - PURPOSE: This paper briefly summarizes the research on increased radiosensitivity
      in breast cancer patients measured by the micronucleus test (MNT) and its
      association to genetic variants in DNA repair genes. More preliminary data are
      presented on the distribution of chromosomes and chromosome fragments in
      micronuclei (MN) in order to gain more information on clastogenic and aneugenic
      effects and better understand the phenotype of increased radiosensitivity.
      MATERIAL AND METHODS: Reports of relevant studies obtained from a search of
      PubMed and studies referenced in those reports were reviewed. In four patients
      with high MN frequency (three cancer patients, one control) and four probands
      with low MN frequency, the presence of chromosome fragments or whole chromosomes
      in MN was determined by fluorescence in situ hybridization analysis for
      chromosomes 1, 7, and 17. RESULTS: An increased MN frequency in breast cancer
      patients compared to controls has consistently been reported with high
      significance. Higher MN frequencies were observed in 20-50% of breast cancer
      patients. Chromosomal fragments of chromosome 17, but not of chromosomes 1 and 7
      were more frequent in the probands with high MN frequency than in those with low
      frequency (p = 0.045). CONCLUSION: The MNT detects a cellular phenotype common to
      a portion of sporadic breast cancer patients. This phenotype is very likely to be
      genetically determined. For the genetic dissection of breast cancer
      susceptibility this phenotype may turn out to be more efficient than breast
      cancer itself. Additional parameters which can be measured simultaneously with
      the MN frequency may be able to further enhance its usefulness.

PMID- 18040609
TI  - DEGRO practical guidelines for radiotherapy of breast cancer I: breast-conserving
      therapy.
AB  - BACKGROUND: The present paper is an update of the practical guidelines for
      radiotherapy of breast cancer published in 2006 by the breast cancer expert panel
      of the German Society of Radiation Oncology (DEGRO) [34]. These recommendations
      have been elaborated on the basis of the S3 guidelines of the German Cancer
      Society that were revised in March 2007 by an interdisciplinary panel [18].
      METHODS: The DEGRO expert panel performed a comprehensive survey of the
      literature, comprising lately published meta-analyses, data from recent
      randomized trials and guidelines of international breast cancer societies,
      referring to the criteria of evidence- based medicine [25]. In addition to the
      more general statements of the German Cancer Society, this paper emphasizes
      specific radiotherapeutic aspects. It is focused on radiotherapy after breast
      conserving surgery. Technique, targeting, and dose are described in detail.
      RESULTS: Postoperative radiotherapy significantly reduces rates of local
      recurrence. The more pronounced the achieved reduction is, the more substantially
      it translates into improved survival. Four prevented local recurrences result in
      one avoided breast cancer death. This effect is independent of age. An additional
      boost provides a further absolute risk reduction for local recurrence
      irrespective of age. Women > 50 years have a hazard ratio of 0.59 in favor of the
      boost. For DCIS, local recurrence was 2.4% per patient year even in a subgroup
      with favorable prognostic factors leading to premature closure of the respective
      study due to ethical reasons. For partial-breast irradiation as a sole method of
      radiotherapy, results are not yet mature enough to allow definite conclusions.
      CONCLUSION: After breast-conserving surgery, whole-breast irradiation remains the
      gold standard of treatment. The indication for boost irradiation should no longer
      be restricted to women <or= 50 years. Partial-breast irradiation is still an
      experimental treatment and therefore discouraged outside controlled clinical
      trials. Omission of radiotherapy after breast-conserving surgery of DCIS should
      be restricted to individual exceptions.

PMID- 18040610
TI  - Evaluation of calculation algorithms implemented in different commercial planning
      systems on an anthropomorphic breast phantom using film dosimetry.
AB  - PURPOSE: To evaluate the accuracy of dose calculation algorithms of different
      planning systems for postoperative tangential radiotherapy in breast cancer.
      MATERIAL AND METHODS: On a CT dataset of an anthropomorphic phantom, a structure
      set of the left lung, clinical target volume (CTV), planning target volume,
      heart, and external contour were delineated. The dataset was processed by six
      radiation oncology centers participating in this multicenter dosimetry project.
      Conventional plans with two tangential wedged fields were generated in
      MasterPlan, Pinnacle, Eclipse, TMS, and PrecisePLAN. Plan calculations were done
      using the beam data of local linacs. The dose distributions were verified under
      local conditions with Gafchromic-EBT films. RESULTS: In all planning systems,
      deviations between calculation and measurement were around +/-3% in the CTV in
      the measured plane. Only small areas with deviations of +/-5% were detected.
      Pencil-beam (PB) calculations overestimated the dose inside the lung by up to
      23%. Collapsed cone (CC) underestimated the lung dose by up to 6%. CONCLUSION: CC
      calculates the dose distribution more accurately than PB. Inside regions with
      electron disequilibrium, however, the dose is slightly underestimated.

PMID- 18040611
TI  - Stereotactic single-dose radiotherapy of lung metastases.
AB  - BACKGROUND: Stereotactic treatment approaches lead to a significant reduction of
      irradiated volumes, which should make pulmonary targets more accessible to
      radiotherapy. PATIENTS AND METHODS: Between May 1997 and December 2005, 61
      patients received stereotactic single-dose dose treatment for 71 pulmonary
      metastases. Doses to the isocenter ranged from 12 to 30 Gy. Survival and local
      tumor control rates were evaluated prospectively. RESULTS: After a median follow
      up period of 14 months the actuarial overall survival was 78.4%, 65.1%, and 47.8%
      12, 24, and 36 months after therapy, respectively. There was a significantly
      better survival (p = 0.023) for patients not developing further metastases during
      follow-up. The actuarial local progression-free rate was 88.6%, 73.7%, and 63.1%
      12, 24, and 36 months after therapy. Although the majority of patients (70.4%)
      developed perifocal normal-tissue changes, these were not related to clinically
      relevant toxicities. CONCLUSION: Stereotactic single-dose radiotherapy is a
      feasible, safe and effective local treatment option for solitary pulmonary
      metastases in patients with contraindications to surgery or for palliation of
      symptomatic pulmonary metastases.

PMID- 18040613
TI  - Novel technique of craniospinal axis proton therapy with the spot-scanning
      system: avoidance of patching multiple fields and optimized ventral dose
      distribution.
AB  - BACKGROUND AND PURPOSE: Conventional craniospinal irradiation (CSI) is a complex
      procedure carrying a high risk of adverse side effects. Still, it is
      indispensable for cure in a number of pediatric brain tumors. In this study, the
      feasibility and the potential advantage of spot-scanning proton therapy for CSI
      are investigated. MATERIAL AND METHODS: A boy (5.5 years of age) with a recurrent
      medulloblastoma received CSI with a single posterior field using the spot
      scanning system at Paul Scherrer Institute. Dose distribution to the targets and
      the organs at risk, treatment time, reproducibility of patient positioning,
      toxicity (according to EORTC/RTOG score), and treatment outcome were evaluated.
      RESULTS: The plan achieved a homogeneous coverage of the target volume, even
      using a single field. The doses to the organs ventral to the target were
      minimized. During treatment, grade 1 skin reaction and grade 2 central nervous
      system toxicity were observed. After 2 months, the boy presented with a
      transitory fatigue. After 24 months, he is alive and free of disease. Growth
      hormones and thyroid hormones are reduced. CONCLUSION: These results, based on a
      single patient, suggest that spot-scanning proton therapy for craniospinal
      treatment is feasible and safe. By applying a single dorsal field, difficulties
      of multiple-field patching can be avoided and the ventral dose spread can be
      minimized.

PMID- 18040612
TI  - Surgery and chemotherapy for small cell lung cancer in stages I-II with or
      without radiotherapy.
AB  - PURPOSE: To analyze the effectiveness of surgery and chemotherapy with or without
      radiotherapy in the management of limited small cell lung cancer (LSCLC) in
      stages I and II. PATIENTS AND METHODS: 39 patients (median age 62 years) with
      LSCLC in stages pT1 or pT2 and pN0 or pN1 (stages IA-IIB) who had a tumor
      resection and systematic lymph node dissection were reviewed retrospectively. The
      median follow-up period was 29 months. 35 patients (90%) received a median of
      four cycles of a platinum-containing chemotherapy postoperatively. 16 patients
      (41%) received an adjuvant thoracic radiotherapy (TRT, median 50 Gy); 21 patients
      (54%) received a prophylactic cranial irradiation (PCI, median 30 Gy). RESULTS:
      The median overall survival for all patients was 47 months, resulting in
      actuarial 1-, 3-, and 5-year survival rates of 97%, 58%, and 49%, respectively.
      Distant metastases were found in 13 patients (33%) after a median of 16 months.
      Patients who received an adjuvant TRT showed a trend toward improved thoracic
      recurrence-free survival (p = 0.06) and improved overall survival (p = 0.07)
      compared to those treated with surgery and chemotherapy only. Brain metastasis
      free survival (p = 0.01) and overall survival (p = 0.01) were improved
      significantly in patients who received a PCI. CONCLUSION: Surgical tumor
      resection may be considered for carefully selected patients. Adjuvant
      chemotherapy and PCI are recommended for all patients. Adjuvant TRT is currently
      used in patients with positive lymph nodes (pN1), because the probability of a
      subclinical involvement of the mediastinal lymphatic system appears to be
      increased in these patients.

PMID- 18040614
TI  - Delineation of target volume for radiotherapy of high-grade gliomas by 99m Tc
      MIBI SPECT and MRI fusion.
AB  - BACKGROUND AND PURPOSE: Computed tomography (CT) and magnetic resonance imaging
      (MRI) are traditionally used for treatment planning of high-grade glioma. 99m Tc
      methoxy-isobutyl-isonitrile (MIBI) single-photon emission computed tomography
      (SPECT) showed high sensitivity and specificity in literature series. In the
      present study, it was investigated how the information provided by 99m Tc-MIBI
      SPECT and MRI fusion could affect target delineation for radiotherapy of high
      grade glioma. PATIENTS AND METHODS: 21 patients with high-grade glioma were
      studied by MRI and 99m Tc-MIBI SPECT imaging. The gross tumor volume (GTV) was
      outlined on MRI (MRI-GTV) and SPECT images (SPECT-GTV). Three additional volumes
      were analyzed: the (MRI+SPECT)-GTV representing the whole amount of MRI-GTV plus
      SPECT-GTV, the (MRI&SPECT)-GTV identified by the overlapping region of MRI-GTV
      and SPECT-GTV, and the (SPECT/MRI)-GTV identified by the extension of SPECT-GTV
      outside MRI-GTV. RESULTS: MRI contrast-enhanced and 99m Tc-MIBI SPECT-positive
      lesions were found in all 21 patients. The average SPECT-GTV was slightly larger
      than the average MRI-GTV, with greater difference for resected than for
      unresected cases. The average increment of (MRI+SPECT)-GTV compared to MRI-GTV
      was 33%, being significantly higher for resected than for unresected cases (p =
      0.006). CONCLUSION: The fusion of 99m Tc-MIBI SPECT and MRI significantly
      affected the delineation of the target volume identified by MRI alone.

PMID- 18040616
TI  - Psychiatric challenges throughout the life span. Abstracts of the Second Meeting
      of West European Societies of Biological Psychiatry. December 13-15, 2007.
      Strasbourg, France.

PMID- 18040615
TI  - Postoperative radiotherapy of glioblastoma multiforme: analysis and critical
      assessment of different treatment strategies and predictive factors.
AB  - BACKGROUND AND PURPOSE: Different factors influence glioblastoma patients'
      prognosis. The aim of this retrospective, explorative analysis was to define the
      role of recent treatment strategies and to examine the value of different
      prognostic factors. PATIENTS AND METHODS: A total of 110 patients was analyzed.
      Complete resection, partial resection, and biopsy was accomplished in 69, 22, and
      19 patients, respectively. 56 patients received conventionally fractionated
      radiotherapy with a median total dose of 60 Gy, 2 Gy daily. 54 patients received
      hyperfractionated accelerated radiotherapy with a median total dose of 54 Gy, 2 x
      1.8 Gy daily. 20 patients had concomitant temozolomide (50-75 mg/m2/d), and 20
      patients concomitant topotecan (0.5 mg/m2 as continuous venous infusion over 21
      days). 37 patients received temozolomide as salvage therapy. RESULTS: Median
      overall (OS) and disease-free survival (DFS) were 8.7 and 4.8 months. After
      complete resection, partial resection, and biopsy, OS was 9.5, 8.5, and 5.5
      months, respectively. OS was 8.5, 13.8, and 8.2 months for radiotherapy alone,
      concomitant temozolomide, and concomitant topotecan, respectively. Hazard ratio
      was 0.29 (OS; p = 0.002) and 0.32 (DFS; p = 0.003) for concomitant temozolomide
      compared to radiotherapy alone. Topotecan led to an increased toxicity. With 9.7
      months for conventionally fractionated radiotherapy and 8.1 months for
      hyperfractionated radiotherapy, OS differed significantly (p = 0.003, log-rank
      test). OS in patients with RPA (recursive partitioning analysis) score III, IV,
      V, and VI was 14.1, 10, 9.5, and 5.8 months (p = 0.003, log-rank test). In the
      univariate (p = 0.0001, log-rank test) and multivariate analysis (p = 0.002, Cox
      regression), salvage temozolomide led to a statistically significant survival
      benefit (10.6 vs. 7.7 months). CONCLUSION: Concomitant topotecan or the use of
      hyperfractionated radiotherapy did not show to be superior in outcome in this
      retrospective analysis. Topotecan led to an increased toxicity. An attempt at
      complete resection is justified. Temozolomide should be integrated in therapy
      initially. As salvage therapy, temozolomide is also effective.

PMID- 18040617
TI  - Preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels
      for the evaluation of curability and resectability in patients with pancreatic
      adenocarcinoma.
AB  - BACKGROUND PURPOSE: Although carcinoembryonic antigen (CEA) and carbohydrate
      antigen 19-9 (CA 19-9) are the most studied serum tumor markers that have been
      evaluated for diagnosis and prognosis in patients with pancreatic cancer, little
      is known of the value of these markers for the prediction of curability and
      resectability. METHODS: We retrospectively reviewed preoperative serum levels of
      CEA and CA 19-9 in 244 consecutive patients with pancreatic operations. RESULTS:
      Although 159 pancreatic operations seemed "resectable", 93 of them were judged
      curative (R0) and the other 66 turned out to be noncurative (R1/2). The remaining
      85 failed resection because of unexpected metastasis or locally advanced disease
      (LD), which was unresectable compared with levels in those patients without liver
      metastasis or LD. CEA levels were significantly higher in patients with liver
      metastasis and LD, while CA 19-9 levels were correlated with liver and peritoneal
      metastases. When both markers were negative, curative (R0) and respectable (R0 +
      R1/2) operation were performed in 70% and 85% of patients, respectively. Logistic
      regression analysis indicated that under conditions where both CEA and CA 19-9
      were negative, the odds ratios for curative and respectable operations were 4.43
      and 3.58, respectively. CONCLUSIONS: Our data suggest that combined preoperative
      CEA and CA 19-9 levels are suitable for assessing expected curability and
      resectability in patients with pancreatic cancer.

PMID- 18040618
TI  - Prognostic factors for long-term survival in patients with locally invasive
      pancreatic cancer.
AB  - BACKGROUND/PURPOSE: We aimed to investigate predictors of survival in patients
      with resectable locally invasive pancreatic cancer. METHODS: The patient cohort
      consisted of 55 patients with locally invasive pancreatic cancer (International
      Union Against Cancer [UICC] stage III in 36 patients and stage IV in 19) who had
      undergone resection. The patients were informed about the advantages and the
      adverse effects of postoperative chemotherapy, and prospectively selected either
      observation alone or postoperative chemotherapy. The postoperative chemotherapy
      regimen options were: (1) intraarterial chemotherapy alone, (2) systemic
      chemotherapy alone, or (3) intraarterial chemotherapy combined with systemic
      chemotherapy. RESULTS: Overall 1-year and 2-year survival rates after resection
      were 40.5% and 13.5%, respectively. Median survival time was 10.9 months. Twenty
      nine patients (52.7%) received postoperative chemotherapy. On univariate
      analysis, only postoperative chemotherapy was associated with long-term survival
      (P < 0.01). In the patients with postoperative chemotherapy, the 1-year survival
      rate and MST were 61.7% and 16.3 months, compared with 20.1% and 7.9 months in
      the patients without postoperative chemotherapy. Multivariate analysis also
      showed that only postoperative chemotherapy was identified as an independent
      survival factor. CONCLUSIONS: It was suggested that postoperative chemotherapy
      was essential for the improvement of survival in patients with locally invasive
      pancreatic cancer.

PMID- 18040619
TI  - Clinical significance of drainage tube insertion in laparoscopic cholecystectomy:
      a prospective randomized controlled trial.
AB  - BACKGROUND/PURPOSE: We aimed to investigate the appropriateness of inserting an
      intraperitoneal drainage tube after laparoscopic cholecystectomy (LC), based on
      postoperative pain and clinical courses, in a randomized comparative study.
      METHODS: One hundred and twenty patients who were to have LC were enrolled in
      this prospective randomized study. An 8-mm Penrose drain was retained below the
      liver bed for 42 h in each of 60 patients (group A), and no drain was retained in
      the remaining 60 patients (group B). Patients in each group were hospitalized for
      4 days after operation, and the pain reported by the patients, using a visual
      analogue pain scale (VAS), and the time courses of changes in the highest body
      temperature, leukocyte count, and C-reactive protein (CRP) were studied
      comparatively for men and women. RESULTS: Mean VAS scores were significantly
      greater in group A than in group B at 24 h (P = 0.00004), and 48 h (P = 0.0014)
      after operation. When sex-stratified changes in mean VAS scores were compared
      within group A, females had more pain than their male counterparts at 24 h (P =
      0.030), but group B showed no sex differences. When the number of patients who
      used analgesics postoperatively was compared between groups A and B, analgesics
      were used more frequently in group A. When changes in maximum body temperature
      were compared, the change was significantly higher in group A than in group B on
      day 2 after the operation (P = 0.017). CONCLUSIONS: Postoperative pain was
      intensified by the insertion of a drainage tube after LC. This tendency was
      stronger in women.

PMID- 18040620
TI  - Risk factors, predictors and prevention of pancreatic fistula formation after
      pancreatoduodenectomy.
AB  - BACKGROUND/PURPOSE: Although the operative mortality and morbidity associated
      with pancreatoduodenectomy (PD) has been decreasing, pancreatic fistula remains a
      potentially fatal complication. The aim of this study was to identify risk
      factors and predictors of pancreatic fistula formation, and ways to prevent this
      in a consecutive series of PD patients in a single institution. METHODS: The
      association between pancreatic fistula formation and various clinical parameters
      was investigated in 50 patients who underwent PD at Kochi Medical School from
      January 1991 through February 2006. RESULTS: The incidence of pancreatic fistula
      in these patients was 28%. Multivariate analysis identified three independent
      factors correlated with the occurrence of pancreatic fistula: (1) absence of
      fibrotic texture of the pancreas examined intraoperatively (relative risk [RR],
      1.6; 95% confidence interval [CI], 1.2-2.0; P = 0.01); (2) serum amylase
      concentration greater than 195 U/l (1.69 times the normal upper limit) on the
      first postoperative day (RR, 2.4; 95% CI, 1.0-5.7; P = 0.01); and (3) not having
      early postoperative enteral nutrition (RR, 3.2; 95% CI, 1.2-9.0; P = 0.004).
      CONCLUSIONS: Soft texture of the pancreas and increased serum amylase the day
      after PD are both risk factors with predictive value for pancreatic fistula. The
      incidence of fistula formation is reduced by early postoperative enteral
      nutrition.

PMID- 18040621
TI  - Do we need histology for a normal-looking gallbladder?
AB  - BACKGROUND/PURPOSE: Gallbladder cancer (GBC) is a rare malignancy with poor
      overall prognosis. Simple cholecystectomy is curative if the cancer is limited to
      mucosa. We aimed here to investigate the need for routine histological
      examination of gallbladder. METHODS: We carried out a retrospective review of
      2890 final pathology reports of processed gallbladder specimens following
      cholecystectomy due to gallstones disease. The review covered the 10-year period
      from 1994 to 2004. The notes of all cases of gallbladder cancer were scrutinized,
      with particular emphasis on presentation, preoperative diagnostic tools using
      abdominal ultrasound and computed tomography scan, operative findings, and the
      histology results. RESULTS: Gallbladder cancer (GBC) was detected in five
      specimens (0.17%), dysplasia in six (0.2%), and secondaries to gallbladder in
      three (0.1%). Histological findings confirmed gallstone disease in 97% and rare
      benign pathology in 3%. The median age of patients with GBC was 61 years (range,
      59-84 years). In all five patients, cancer was isolated from thickened fibrotic
      wall on macroscopic appearance and spread through all layers of the gallbladder
      wall. The percentage of thickened-wall gallbladder in this study was 38.02% and
      the cancer incidence in the thickened wall was 0.45%. CONCLUSIONS: A selective
      policy rather than routine histological examination of nonfibrotic or thickened
      wall gallbladder has to be considered. This will reduce the burden on pathology
      departments, with significant cost savings.

PMID- 18040622
TI  - Endoscopic pancreatic duct drainage and stenting for acute pancreatitis and
      pancreatic cyst and abscess.
AB  - BACKGROUND/PURPOSE: Endoscopic drainage of pancreatic pseudocysts using
      transpapillary and transmural approaches has been reported. In this study,
      endoscopic nasopancreatic drainage (ENPD) and pancreatic stenting were performed
      in patients with pseudocyst and abscess associated with acute pancreatitis, and
      the usefulness and problems of the procedures were investigated. METHODS: After
      endoscopic retrograde pancreatography was done, ENPD and/or pancreatic stenting
      were performed in 13 patients with pancreatitis and pseudocyst or abscess that
      communicated with the main pancreatic duct. RESULTS: ENPD was performed in seven
      patients, and was effective in all five patients with cysts: the cysts
      disappeared or shrank. However, the condition in the two patients with abscess
      was unchanged, and percutaneous drainage was performed. Stenting was carried out
      in six patients, and the cyst disappeared or pancreatitis was improved in all
      six. The stent was removed from two patients, but no recurrence has been noted so
      far. CONCLUSIONS: ENPD and stenting are effective therapeutic choices for acute
      and chronic pancreatitis and pseudocysts, and they are superior to percutaneous
      drainage to avoid pancreatic fistula, but they may not be effective for
      pancreatic abscess. Selection of therapeutic methods corresponding to individual
      cases is important.

PMID- 18040623
TI  - Pancreatoduodenectomy in which dissection of the efferent arteries of the head of
      the pancreas is performed first.
AB  - BACKGROUND/PURPOSE: Pancreatoduodenectomy (PD) is one of the most difficult
      operations in gastrointestinal surgery. Standard PD ligates and cuts superior
      mesenteric vein (SMV) branches after the removal of the pancreas head, which
      leads to congestion and bleeding of these veins. METHODS: In this study, we
      modified the standard PD and first ligated the efferent vessels (arteries);
      namely, the gastroduodenal artery and inferior pancreatoduodenal artery (IPDA),
      before ligating and cutting the corresponding afferent vessels (veins) of the
      pancreas head. By doing this, congestion of these veins was relieved and bleeding
      from the resected surface was substantially prevented. Thirty-six patients (18
      underwent standard PD and 18 had modified PD) formed the study population.
      RESULTS: The amount of bleeding in the modified PD group was significantly lower
      than that in the standard PD group. (678 +/- 329 g vs 1225 +/- 375 g,
      respectively; P < 0.05) However, no difference in operation time was found
      between the two groups. CONCLUSIONS: We believe this modified PD procedure is
      valuable to enable the safe performance of PD.

PMID- 18040624
TI  - Spontaneous idiopathic subcapsular biloma.
AB  - Spontaneous biloma is an uncommon entity. We report a case of subcapsular biloma
      in an elderly patient with a nonobstructed biliary channel, without prior history
      of surgery, instrumentation, or trauma. Computed tomography (CT) and magnetic
      resonance imaging are described. We believe that this is the first reported case
      of spontaneous subcapsular biloma of idiopathic origin.

PMID- 18040625
TI  - Three pulmonary resections for metastatic lung cancer from hepatocellular
      carcinoma.
AB  - We describe a patient who underwent pulmonary resection three times for
      metastatic lung cancer from hepatocellular carcinoma (HCC). A 56-year-old man,
      who had a past history of right hepatic lobectomy for HCC, was referred to our
      department with an abnormal finding on chest computed tomography (CT). Chest CT
      showed three abnormal shadows, in the right upper lobe (S3b), right middle lobe
      (S5), and right lower lobe (S10), respectively, and there was no evidence of
      intrahepatic recurrence. He underwent surgical resections (right upper lobectomy
      and partial resections) for the metastatic lung cancer from HCC. Subsequently, 12
      and 16 months after the first pulmonary resection, metastatic lung cancer
      recurred, in right S6 and S9, respectively. Because there was no evidence of
      intrahepatic recurrence and because of the feasibility of curative resection, we
      performed partial pulmonary resections. He had no postoperative morbidity, and is
      alive with no evidence of disease 60 months after the first pulmonary resection.
      Twelve cases of repeat pulmonary resections for metastatic lung cancer from HCC
      have been reported in the literature, and the authors of these reports described
      that repeated pulmonary resections for metastatic lung cancer from HCC resulted
      in long-term survival. Repeat pulmonary resections for metastatic lung cancer
      from HCC can be an effective treatment for patients with such metastases.

PMID- 18040626
TI  - Cystic endocrine tumor of the pancreas with an atypical multilocular appearance.
AB  - A 46-year-old woman with epigastric pain was found to have a cystic tumor in the
      pancreas head on radiological examinations. The tumor was hypervascular, and its
      multilocular appearance resembled the "honeycomb" pattern of serous cystic tumor
      (SCT). The patient underwent surgery. The cut surface of the tumor showed a thick
      fibrous capsule with multiple cystic components, which contained necrotic tissue
      and brownish serous fluid, indicating an episode of hemorrhage. The cut surface
      of the tumor resembled solid-pseudopapillary tumor (SPT) on gross appearance. On
      immunohistochemical staining, the tumor cells showed diffuse and strong staining
      for synaptophysin (SYN), chromogranin A (CGA), and grimelius, and no staining for
      alpha 1-antitrypsin or CD10. We finally made a diagnosis of pancreatic endocrine
      tumor (PET). As PET sometimes shows an atypical multicystic appearance,
      immunohistochemical staining is mandatory for its correct diagnosis.

PMID- 18040627
TI  - Rectal cancer metastasis to the head of the pancreas treated with
      pancreaticoduodenectomy.
AB  - We report a case of a 50-year-old man who developed metastatic pancreatic cancer
      from a primary rectal cancer that had been curatively removed 3 years previously.
      The patient presented with a tumor that occupied the head of the pancreas,
      associated with obstructive jaundice, but the main pancreatic duct was not
      dilated. The patient was initially diagnosed as having primary pancreatic cancer.
      Cytological examination of the bile was conclusive for the presence of
      adenocarcinoma. The patient refused surgical treatment and chose to have
      gemcitabine therapy (1000 mg/body), which was given 27 times over 10 months. For
      1 year, local disease progression was slow and no distant metastases developed;
      therefore, the initial diagnosis of pancreatic cancer was questioned. At that
      time, the patient asked for the tumor to be removed, and pancreaticoduodenectomy
      was performed. On histology, including immunohistochemical staining for
      cytokeratin 20 (positive) and cytokeratin 7 (negative), the tumor was shown to be
      a metastatic pancreatic carcinoma that had originated from the original rectal
      cancer.

PMID- 18040628
TI  - Malignant transformation of a solitary fibrous tumor of the liver and intractable
      hypoglycemia.
AB  - Sarcomas of the liver are rare. We report a case of intractable hypoglycemia
      secondary to a solitary fibrous tumor that underwent malignant transformation
      into a fibrosarcoma. A 70-year-old man presented with a hepatic mass and tumor
      associated hypoglycemia which was resistant to medical management. Blood tests
      were remarkable only for elevated serum insulin-like growth factor (IGF)-2. The
      hypoglycemia resolved following resection of a solitary fibrous tumor surrounded
      by a high-grade fibrosarcoma. Real time reverse transcriptase polymerase chain
      reaction (RT-PCR) measured elevated levels of IGF2 mRNA in both the solitary
      fibrous tumor and the fibrosarcoma. Immunoblotting demonstrated a series of bands
      in the size range of pro-IGF2. Unfortunately, disseminated metastases developed 1
      year later, concurrent with a recurrence of hypoglycemia, marked again by
      elevation of serum IGF2. Solitary fibrous tumors of the liver have a real risk of
      malignant transformation. The severity of the tumor-associated hypoglycemia may
      parallel the tumor burden and activity. The syndrome is the systemic effect of
      IGF2 secreted by the tumor. Surgery can treat the hypoglycemia syndrome and the
      underlying malignancy.

PMID- 18040629
TI  - Multiple synchronous serous cystadenomas of the pancreas: uncommon CT and MRI
      findings.
AB  - Serous cystadenomas (SCAs) of the pancreas are benign cystic tumors. Although
      still controversial, asymptomatic SCAs, in contrast to their mucinous
      counterparts, can be treated conservatively. This attitude is mostly defendable
      for lesions of the pancreas head or multiple lesions distributed throughout the
      entire pancreas, as their surgical resection is still associated with significant
      morbidity. Thus, correct diagnosis is essential, and this relies on radiological
      and biological characteristics. Asymptomatic multiple SCAs are rare. Most cases
      described in the literature are either symptomatic, degenerated, or both. We
      present a case of huge (>10 cm), multiple asymptomatic SCAs, not associated with
      von Hippel-Lindau disease, involving the entire pancreas. The patient has been
      followed up for 3 years and remains asymptomatic. Tumor markers were within
      normal ranges. On abdominal computed tomography (CT) and magnetic resonance
      imaging (MRI), the lesions showed pathognomonic characteristics of SCAs, and
      their uncommon dimensions and number remained stable over time. 18
      Fluorodeoxyglucose positron emission tomography (PET) scan performed at 3-year
      follow-up did not show hypermetabolic lesions.

PMID- 18040630
TI  - Anomalous intrahepatic portal system in a patient with hilar bile duct cancer.
AB  - We report a case of anomaly of the intrahepatic portal system in a 65-year-old
      man with hilar bile duct cancer. Preoperatively, percutaneous transhepatic
      portography demonstrated that there was a right posterior portal vein arising
      from the main portal vein. In addition, a large portal branch originated from the
      left portal vein and coursed toward the right hepatic lobe. Following portal
      embolization of the right posterior branch, the patient underwent an extended
      right hepatectomy with a caudate lobectomy. Intraoperatively, to the left at the
      porta hepatis and then it first gave off the right anterior portal vein
      originated from the left portal vein and coursed toward the right hepatic lobe
      horizontally behind the gallbladder and then separated into superior and inferior
      segmental branches to supply the right anterior segment of the liver. The
      ramification of some major branches without malposition of the gallbladder or
      round ligament was the important clinical feature of this anomaly.

PMID- 18040631
TI  - Gallbladder torsion-induced emphysematous cholecystitis in a 16-year-old boy.
AB  - The patient was a 16-year-old boy who had turned to the right rapidly as he
      fielded a baseball that had come to him quickly. Two days after this event, which
      occurred in July 2004, he was admitted to hospital with repeated vomiting and
      increasing right hypochondralgia. Laboratory examination on admission showed
      elevation of the white blood count and of serum C-reactive protein and total
      bilirubin. Computed tomography on admission demonstrated an enlarged gallbladder
      and a thickened wall without gallstones, and magnetic resonance imaging performed
      1 day later showed air within the gallbladder wall. His symptoms worsened, with a
      positive Murphy's sign, and emergency laparotomy was performed, with a diagnosis
      of emphysematous cholecystitis. Intraoperatively, the gallbladder was dark red,
      necrotic, distended, and enlarged. The cystic duct was attached only to the
      mesentery, and the gallbladder was floating freely, with the neck of the
      gallbladder having rotated 180 degrees counterclockwise, leading to a definitive
      diagnosis of gallbladder torsion with emphysematous cholecystitis.
      Cholecystectomy was performed, and analysis of bile showed Escherichia coli to be
      the causative organism. Histopathologic examination revealed necrotized
      cholecystitis. The patient is doing well 25 months after surgery, with an
      uneventful postoperative course.

PMID- 18040632
TI  - Arrogant misquotations from reference citations.

PMID- 18040633
TI  - Current trends in bone grafting and the issue of banked bone allografts based on
      the fourth nationwide survey of bone grafting status from 2000 to 2004.
AB  - BACKGROUND: The Japanese Orthopaedic Association Committee on Tissue
      Transplantation and Regenerative Medicine has conducted a nationwide survey of
      the status of bone grafting in Japan every 5 years from 1985. We report here the
      status of bone grafting from 2000 to 2004, show the trends in bone grafting from
      1985 to 2004, and draw attention to the issues affecting banked bone allografts.
      METHODS: Questionnaires devised by the Committee were sent to all educational and
      training hospitals (2239 institutions) approved by the Japanese Orthopaedic
      Association. RESULTS: Survey responses were obtained from 1263 institutions
      (56%). Of these, 875 institutions performed tissue transplantation during this
      period. A total of 163 564 tissue transplantations were performed, and 134 782
      (82.4%) of them were bone grafts. Of the bone grafts, 76 015 (56.4%) were
      autografts, 53 735 (40%) used a synthetic bone substitute, and 4886 (3.6%) were
      banked bone allografts. The proportion of synthetic bone substitutes increased,
      and the proportion of autografts decreased year by year. Synthetic bone
      substitutes were most frequently used for replacement arthroplasty (31%). Fifty
      percent of banked bone allografts were performed for joint disorders requiring
      replacement arthroplasty. During this period, 271 institutions performed banked
      bone allografts, with 210 preserving allografts in their own institutions. Donor
      selection criteria, processing and preservation methods, and management of the
      bone bank were not the same in all banks. CONCLUSIONS: Most bone grafts performed
      in Japan during the four surveys were still autografts. However, the proportion
      of autografts decreased, and the proportion of synthetic bone substitutes
      increased. The number of synthetic bone substitutes and banked bone allografts
      used for replacement arthroplasty increased significantly. However, the total
      number of banked bone allografts reported in the fourth survey was still low.
      Quality control of banked bone allografts and management of bone banks were not
      satisfactory, although they were improved.

PMID- 18040634
TI  - Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. Part 2.
      Verification of its reliability : The Subcommittee on Low Back Pain and Cervical
      Myelopathy Evaluation of the Clinical Outcome Committee of the Japanese
      Orthopaedic Association.
AB  - BACKGROUND: The project to develop a new Japanese Orthopaedic Association (JOA)
      score rating system for low back disorders, the JOA Back Pain Evaluation
      Questionnaire (JOABPEQ), is currently in progress. Part 1 of the study selected
      25 "candidate" items for use on the JOABPEQ. The purpose of this current Part 2
      of the study was to verify the reliability of the questionnaire. METHODS: A total
      of 161 patients with low-back disorders of any type participated in the study.
      Each patient was interviewed twice at an interval of 2 weeks using the same
      questionnaire. The reliability of the questionnaire was evaluated by determining
      the extension of the kappa and weighted kappa coefficients. RESULTS: Both kappa
      and weighted kappa were more than 0.50 for all but one item, which was 0.48. The
      lower 95% confidence interval exceeded 0.4 in all but two items, which was 0.39.
      This implied that the test-retest reliability of JOABPEQ was acceptable as a
      measure of outcome. CONCLUSIONS: The tentative questionnaire of the JOABPEQ with
      25 items was confirmed to be reliable enough to describe the quality of life of
      patients who suffer low back disorders.

PMID- 18040635
TI  - Imaging characteristics of deep-seated lipomatous tumors: intramuscular lipoma,
      intermuscular lipoma, and lipoma-like liposarcoma.
AB  - BACKGROUND: Lipoma-like liposarcomas mimic deep-seated lipomas in regard to
      imaging as well as histological findings and occasionally cause problems
      concerning diagnosis and treatment. The differences in the imaging findings among
      these lesions are not well defined. The purpose of this study was to elucidate
      the differences among the deep-seated adipocytic neoplasms including
      intramuscular lipoma, intermuscular lipoma, and lipoma-like liposarcoma. METHODS:
      The imaging and clinicopathological findings of 40 intramuscular lipomas, 27
      intermuscular lipomas, and 22 lipoma-like liposarcomas were evaluated, and the
      possibilities in the differential diagnosis were assessed. RESULTS: Although the
      most frequent symptom was a palpable mass, swelling was a common symptom of
      intramuscular lipomas and lipoma-like liposarcomas. Imaging studies revealed
      dumbbell-shaped appearances among intermuscular lipomas, whereas spherical masses
      were characteristic of intramuscular lipomas and lipoma-like liposarcomas.
      Computed tomography and magnetic resonance imaging revealed fatty lesions
      containing streaky structures in benign lesions, and CT revealed foci of hazy
      amorphous density, representing spindle cell proliferation, in lipoma-like
      liposarcoma. Although streaky structures corresponding to entrapped muscle fibers
      were thick and occasionally interrupted in intramuscular lipomas, the streaky
      structures corresponding to areolar fibrous tissue were thin and were usually not
      interrupted in intermuscular lipomas. In lipoma-like well-differentiated
      liposarcomas, thick streaks represented entrapped muscle fibers, and thin streaks
      represented fibrous tissue or neoplastic spindle cell proliferation. CONCLUSIONS:
      The imaging findings are helpful and often afford almost pathognomonic evidence
      of these lesions and could help with the selection of appropriate surgery.

PMID- 18040636
TI  - Pasteurized autograft-prosthesis composite for distal femoral osteosarcoma.
AB  - BACKGROUND: We examined the survivorship and functional outcome of the
      pasteurized autograft-prosthesis composite for distal femoral osteosarcoma. We
      also evaluated complications including nonunion, loosening, bony resorption,
      infection, and fracture. METHODS: We retrospectively reviewed 15 distal femoral
      osteosarcoma patients who underwent reconstructions using pasteurized autograft
      prosthesis composite between 1993 and 2003. RESULTS: No patient required graft
      removal during a minimum follow-up of 35 months (average 56 months; range 35-78
      months). The average Musculoskeletal Tumor Society System (MTSS) functional score
      was 86%. Nonunion developed in five patients, and three of them subsequently
      showed loosening of the stem. No patient experienced infection or fracture.
      CONCLUSIONS: Our data suggest that the pasteurized autograft-prosthesis composite
      could be an easily accessible alternative for the reconstruction of large
      skeletal defects in the distal femur because of the satisfactory functional
      outcome with a low rate of ultimate failure and complications in this study.

PMID- 18040637
TI  - Gait analysis of patients in early stages after total hip arthroplasty: effect of
      lateral trunk displacement on walking efficiency.
AB  - BACKGROUND: Control of the mediolateral displacement of the center of gravity
      (COG) is considered to be important for efficient walking. Few studies have been
      published on the relation between walking efficiency and the lateral displacement
      of the trunk, pelvis, or COG in patients soon after total hip arthroplasty (THA).
      The present study was undertaken to examine the effects of lateral displacement
      on walking efficiency after THA. METHODS: The subjects of this study were 15
      women who had undergone unilateral THA 4 weeks before and 14 healthy women as
      controls. Using a force plate and a three-dimensional motion analyzer, we
      measured (1) gait speed, stride length, cadence; (2) lateral trunk displacement
      (LTD) and lateral pelvis displacement (LPD); (3) lateral displacement of the
      center of gravity; and (4) the total internal work done per unit mass and
      distance walked (a negative index of walking efficiency) (WE(-1)). RESULTS:
      Compared with healthy persons, THA patients showed significantly increased
      amplitude of LTD and greater WE(-1) (P < 0.01). The WE(-1) value of the THA group
      was 21.4% higher than that of the control group. The results suggest that the
      patients need more energy to progress their body forward in a gait cycle,
      indicating reduced walking efficiency. In THA patients, the stepwise multiple
      regression analysis selected LTD as the sole significant variable affecting WE(
      1) (R(2) = 0.72, P < 0.01). CONCLUSIONS: These results suggest that trunk
      compensation strategy for hip abductor weakness in patients soon after THA can
      lead to increased energy expenditure.

PMID- 18040638
TI  - Osteogenic protein-1 with transforming growth factor-beta1: potent inducer of
      chondrogenesis of synovial mesenchymal stem cells in vitro.
AB  - BACKGROUND: Recently, cells derived from synovial mesenchymal stem cells (MSCs)
      have been regarded as a potential source of cells to induce repair of articular
      cartilage. To investigate more effective methods for promoting chondrogenesis, we
      examined the effects of osteogenic protein (OP)-1 with or without transforming
      growth factor-beta (TGFbeta1) on chondrogenesis of human MSCs in vitro. METHODS:
      MSCs were isolated from the synovial membrane of patients with rheumatoid
      arthritis undergoing knee replacement surgery. After expansion of the cells,
      pellet cultures were performed in chondrogenic medium with OP-1 100-200 ng/ml,
      TGFbeta1 10 ng/ml, or both agents for 3 or 6 weeks. Chondrogenesis was evaluated
      histologically with safranin O staining, reverse transcription polymerase chain
      reaction for aggrecan and type II collagen mRNA, and quantification of
      glycosaminoglycan (GAG) content using a dimethylmethylene blue dye-binding assay.
      GAG content was normalized by DNA content measured using Hoechst 33258 dye.
      RESULTS: At 3 weeks of culture, mRNAs for type II collagen and aggrecan were
      expressed by MSCs treated with either TGFbeta1 or OP-1; however, substantial
      matrix production was not induced. At 6 weeks, OP-1 increased GAG accumulation
      dose-dependently in the presence or absence of TGFbeta1, and the GAG content was
      the highest after combined treatment with 200 ng OP-1 and TGFbeta1. Histological
      staining for safranin O was poor after treatment with OP-1 or TGFbeta1 alone and
      slightly increased after combined treatment with TGFbeta1 and OP-1 at 3 weeks. At
      6 weeks, OP-1 increased the intensity of staining dose-dependently in the
      presence or absence of TGFbeta1. However, the histological appearance of the
      cells treated with OP-1 alone was similar to that of hypertrophic chondrocytes,
      which was different from that of cells with combined treatment with OP-1 and
      TGFbeta1. CONCLUSIONS: A high dose of OP-1 was useful for enhancing
      chondrogenesis from synovium-derived MSCs in combined treatment with TGFbeta1.

PMID- 18040639
TI  - Prevention of postoperative progression of pulmonary metastases in osteosarcoma
      by antiangiogenic therapy using endostatin.
AB  - BACKGROUND: We have previously offered data suggesting a positive linkage of
      postoperative up-regulation of systemic angiogenic activity and postoperative
      progression of pulmonary metastasis in osteosarcoma. The finding that the
      significant down-regulation of endostatin was critical in angiogenic elevation
      after primary tumor removal suggests that endostatin is a candidate for
      antiangiogenic therapy for osteosarcoma. METHODS: In the current study, we
      evaluated the effect of antiangiogenic therapy using endostatin on postoperative
      progression of pulmonary metastasis from osteosarcoma. Mouse osteosarcoma cell
      line LM 8 cells were inoculated in subcutaneous layer of nude mice. Two weeks
      after tumor inoculation, the primary tumor was removed surgically, and
      antiangiogenic therapy using adenovirus encoding endostatin expression vector
      (Ad5CMV-mEnd) was performed. Two weeks after the antiangiogenic treatment,
      pulmonary metastasis was evaluated by counting the number of metastatic nodules.
      The evaluation of systemic angiogenic activity was performed using Matrigel plug
      assay. RESULTS: Two weeks after the viral injection, mice were sacrificed, and
      the macroscopic pulmonary metastases were counted. Notably, the number of
      pulmonary metastases was smaller in the mice injected with Ad5CMV-mEnd than in
      controls, accompanied by significant suppression of systemic angiogenic activity.
      In addition, the sizes of the pulmonary metastases of the mice injected with
      Ad5CMV-mEnd were smaller than in the control group. CONCLUSIONS: Our results
      indicate that antiangiogenic therapy using endostatin has the potential to
      prevent postoperative progression of pulmonary metastasis from osteosarcoma.
      Although this therapeutic strategy cannot provide a cure for osteosarcoma, it
      should enable osteosarcoma patients to coexist with dormant pulmonary metastasis
      and lead to improvement of their prognosis.

PMID- 18040641
TI  - Effect of lymphedema on the recovery of fractures.
AB  - BACKGROUND: Lymphedema delays the healing of any wound by negatively affecting
      its inflammatory period. Whether it affects bone healing in a similar negative
      manner is unknown. Therefore, we experimentally investigated the effect of
      lymphedema on fracture recovery. METHODS: We used thirty 200- to 250-g Sprague
      Dawley rats for the experiment. The rats were randomly divided into two groups of
      15 rats each for the experimental lymphedema and control groups. Lymphedema
      development was confirmed by measuring the circumference and diameter of the
      extremities together with lymphoscintigraphy. Twenty days after the development
      of lymphedema, a fracture model was created in both groups in the right tibia
      with mid-diaphyseal osteotomy and fixing with an intramedullary Kirschner wire.
      After 6 weeks, all rats were sacrificed and the callus tissue that formed along
      the osteotomy was compared between groups with respect to radiographic,
      histological, and biomechanical characteristics. RESULTS: The three-point bending
      test yielded an average stiffness value of 1227 N/mm (n = 6) in the control group
      and 284 N/mm (n = 7) in the experimental lymphedema group (P < 0.05). At the end
      of week 6, radiographic evaluation showed that solid knitting was obtained in the
      control group, whereas in the lymphedema group delayed or no knitting was
      observed. In the control group, histological investigation revealed normal callus
      morphology. Trabecular bone was normal and osteoblast and osteoclast activity was
      clearly evident. The bone was stained homogeneously with hematoxylin and eosin,
      and ossification was within normal limits. In the lymphedema group, however, the
      histological appearance was mostly that of scar tissue. In addition, osteoblast
      and osteoclast activity was much less visible or absent. CONCLUSIONS: Lymphedema
      negatively affected bone healing in rats. However, the mechanism of this negative
      effect and its occurrence in humans are still unknown. Further experimental and
      clinical studies are needed to support and extend our findings.

PMID- 18040640
TI  - Effect of etidronate on COX-2 expression and PGE(2) production in macrophage-like
      RAW 264.7 cells stimulated by titanium particles.
AB  - BACKGROUND: The most common failure of total joint replacement is aseptic
      loosening in association with osteolysis. Previous reports have shown that
      prostaglandin E(2) (PGE(2)) secreted from macrophages that phagocytosed wear
      debris induced periprosthetic osteolysis. Many clinical studies have reported
      that bisphosphonate therapy reduced periprosthetic bone loss and loosening of the
      implants after total joint replacements. Bisphosphonates are synthetic compounds
      with the ability to decrease bone resorption. In addition, some bisphosphonates
      have been reported to have anti-inflammatory effects by reducing the secretion of
      pro-inflammatory cytokines. However, the mechanism of bisphosphonates that
      reduces periprosthetic bone resorption remains unclear. The purpose of this study
      was to investigate one of the mechanisms by which etidronate (EHDP) inhibits
      periprosthetic bone resorption. METHODS: Macrophage-like RAW 264.7 cells were
      treated with EHDP at concentrations of 0.001, 0.01, 0.1, 1, 10, and 100 microM
      together with the titanium particles at a concentration of 1 mg/ml. After a 24-h
      culture period, total mRNA was isolated and reverse transcription-polymerase
      chain reaction (RT-PCR) was done to examine the expression of cyclooxygenase-2
      (COX-2). The supernatants were also collected and production of PGE(2),
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor
      alpha (TNF-alpha) were quantified using an enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Analyses showed that COX-2 expression and PGE(2) production
      were suppressed by EHDP in a dose-dependent manner. By 100 microM of EHDP, PGE(2)
      production of the cells was suppressed approximately to the level of the
      nonstimulated cells. Production of IL-1beta, IL-6, and TNF-alpha in the
      supernatant was also suppressed by EHDP. CONCLUSIONS: The blockage effect of pro
      inflammatory cytokines is a possible etidronate mechanism that reduces bone
      resorption around implants.

PMID- 18040642
TI  - Successful treatment of nonclostridial gas gangrene extending from
      retroperitoneum to thigh associated with occult cecal cancer.

PMID- 18040643
TI  - Exceedingly large femoral condyle intraosseous ganglion cyst following high
      tibial osteotomy.

PMID- 18040644
TI  - Juxta-facet hematoma.

PMID- 18040645
TI  - Imaging characteristics of calcified leiomyoma of deep soft tissue.

PMID- 18040646
TI  - Solitary bone metastasis as the first clinical manifestation in a patient with
      small bowel adenocarcinoma.

PMID- 18040647
TI  - Effects on kidney disease, fertility and development in mice inheriting a protein
      truncating Denys-Drash syndrome allele (Wt1tmT396).
AB  - Denys-Drash syndrome (DDS) is caused by heterozygous mutations of the Wilms'
      tumour suppressor gene, WT1, characterised by early-onset diffuse mesangial
      sclerosis often associated with male pseudohermaphroditism and/or Wilms'
      tumourigenesis. Previously, we reported that the Wt1tmT396 allele induces DDS
      kidney disease in mice. In the present study heterozygotes (Wt1tmT396/+) were
      generated on inbred (129/Ola), crossbred (B6/129) and MF1 second backcross (MF1
      N2) backgrounds. Whereas male heterozygotes on each background were fertile,
      inbred heterozygous females were infertile. Kidney disease (proteinuria and
      sclerosis) was not congenital and developed significantly earlier in inbred mice,
      although with variable onset. Disease onset in MF1-N2 stocks occurred later in
      Wt1tmT396/+ mice than reported previously for Wt1R394W/+ mice, and while no
      kidney disease has been reported in B6/129 Wt1+/- mice, B6/129 Wt1tmT396/+ mice
      were affected. Offspring of both male and female B6/129 and MF1-N2 Wt1tmT396/+
      mice developed kidney disease, but its incidence was significantly higher in
      offspring of female heterozygotes. Wt1tmT396/tmT396 embryos exhibited identical
      developmental abnormalities to those reported for Wt1-/- embryos. The results
      indicate that the Wt1 (tmT396) allele does not predispose to Wilms'
      tumourigenesis or male pseudohermaphroditism, its effect on kidney disease and
      female fertility depends on genetic background, stochastic factors may affect
      disease onset, and disease transmission is subject to a partial parent-of-origin
      effect. Since the Wt1tmT396 allele has no detectable intrinsic functional
      activity in vivo, and kidney disease progression is affected by the type of Wt1
      mutation, the data support the view that DDS nephropathy results from a dominant
      negative action rather than WT1 haploinsufficiency or gain-of-function.

PMID- 18040648
TI  - [Complex fracture of the proximal humerus in the elderly. Locking plate
      osteosynthesis vs hemiarthroplasty].
AB  - BACKGROUND: The purpose of the present study was a direct comparison of fixed
      angle plate fixation (FAPF) and shoulder hemiarthroplasty (SHA) for complex
      fractures of the proximal humerus in the elderly. PATIENTS AND METHODS: A single
      institution case series of 52 consecutive geriatric patients (age > or =70 years)
      treated with FAPF for three- and four-part fractures of the proximal humerus
      between 2003 and 2005 was analysed 1 year after surgery. The analysis included
      Constant Score (CS), Oxford Shoulder Score (OSS), and radiological evaluation.
      Outcome was compared with a similar historic group of patients (n=59) who
      received SHA in an earlier period (1995--1997). RESULTS: The patient groups
      showed no differences in age, gender, or fracture type. Median CS was
      significantly better for FAPF (71 vs 41). Evaluation of pain demonstrated no
      differences between the two treatment modalities in the OSS. Revision surgery was
      performed more often in the FAPF group (25% vs 2%). CONCLUSION: Compared to SHA,
      functional outcome was superior with FAPF. However, this was associated with a
      higher rate of revision surgery. Most patients were still able to live
      independently in their original environment, regardless of the type of surgery.

PMID- 18040649
TI  - [Hepaticolithiasis. Rare benign disease of the intrahepatic bile ducts].
AB  - Hepaticolithiasis is a rare disease of the intrahepatic bile ducts endemic to
      east Asia which also is known as oriental cholangiohepatitis. Beside strictures
      and metabolic disturbance, the main cause of intrahepatic stones is acquired or
      congenital malformation of the intrahepatic biliary ducts. In the following we
      show a case of hepaticolithiasis and concurrent pancreatic metaplasia.

PMID- 18040651
TI  - [An infant with pustules an both soles].

PMID- 18040650
TI  - [Genital herpes and HSV transmission in HIV patients].
AB  - There is a bidirectional relationship between HSV-2 and HIV-1, both at the
      cellular level, as well as regarding transmission and even progression of HIV-1
      infection. There is clear evidence that anti-herpetic therapy reduces the plasma
      and mucosal HIV-1 viral load, as well as transmission. Serologic testing for HSV
      2 in patients with an increased HIV-1 risk, coupled with a better understanding
      of the interaction between the viruses and appropriate anti-herpetic suppression
      therapy could both reduce the HIV-1 transmission rate and help the individual
      with an HIV infection.

PMID- 18040652
TI  - [Bilateral enlargement of the parotid glands in an HIV-positive patient].

PMID- 18040653
TI  - [New writing direction for the journal HNO].

PMID- 18040654
TI  - Hypoxia and chronic lung disease.
AB  - The lung is both the conduit for oxygen uptake and is also affected by hypoxia
      and hypoxia signaling. Decreased ventilatory drive, airway obstructive processes,
      intra-alveolar exudates, septal thickening by edema, inflammation, fibrosis, or
      damage to alveolar capillaries will all interpose a significant and potentially
      life-threatening barrier to proper oxygenation, therefore enhancing the
      alveolar/arterial pO2 gradient. These processes result in decreased blood and
      tissue oxygenation. This review addresses the relationship of hypoxia with lung
      development and with lung diseases. We particularly focus on molecular mechanisms
      underlying hypoxia-driven physiological and pathophysiological lung processes,
      specifically in the infant lung, pulmonary hypertension, and chronic obstructive
      pulmonary disease.

PMID- 18040655
TI  - [Suspected Alzheimer's disease. Selection of outpatients for neuropsychological
      assessment].
AB  - BACKGROUND: Incipient Alzheimer's disease (AD) is frequently suspected by
      neurologists and psychiatrists, but diagnosis is difficult to establish. The aim
      of this report was to analyse to what extent suspicion is confirmed by a
      comprehensive neuropsychological examination intended to distinguish different
      types of dementia. METHODS: Descriptive data analysis was used for investigating
      the differential diagnoses of 47 outpatients with suspected AD referred to a
      department of neuropsychology by physicians in private practice. Data analysis
      was based upon the NINCDS-ADRDA diagnostic criteria of AD. RESULTS: Only 38% of
      the outpatients examined with suspected AD met the NINCDS-ADRDA diagnostic
      criteria for AD or mixed dementia from a neuropsychological point of view,
      whereas 22% met criteria for other types of dementia. The remaining patients met
      criteria for distinct differential diagnoses (23%) or lacked pathological
      findings in neuropsychological functions (17%). CONCLUSIONS: Neuropsychology is
      an essential part in the differential diagnosis of mild to moderate dementias. It
      can aid in differential therapeutic considerations concerning the treatment of
      dementia, for example in selecting appropriate treatments or avoiding expensive
      but inappropriate ones.

PMID- 18040656
TI  - FT genome A and D polymorphisms are associated with the variation of earliness
      components in hexaploid wheat.
AB  - The transition from vegetative to floral meristems in higher plants is determined
      by the coincidence of internal and environmental signals. Contrary to the
      photoperiod pathway, convergent evolution of the cold-dependent pathway has
      implicated different genes between dicots and monocots. Whereas no association
      between natural variation in vernalization requirement and Flowering time locus T
      (FT) gene polymorphism has been described in Arabidopsis, recent studies in
      Triticeae suggest implication of orthologous copies of FT in the cold response.
      In our study, we show that nucleotide polymorphisms on A and D copies of the
      wheat FT gene were associated with variations for heading date in a collection of
      239 lines representing diverse geographical origins and status (landraces, old or
      recent cultivars). Interestingly, polymorphisms in the non-coding intronic region
      were strongly associated to flowering variation observed on plants grown without
      vernalization. But differently from VRN1, no epistatic interaction between FT
      homeologous copies was revealed. In agreement with the results of association
      study, the A and D copies of FT were mapped in regions including major QTLs for
      earliness traits in hexaploid wheat. This work, by identifying additional
      homeoalleles involved in wheat vernalization pathway, will contribute to a better
      understanding of the control of flowering, hence providing tools for the breeding
      of varieties with enhanced adaptation to changing environments.

PMID- 18040657
TI  - Structures of the three homoeologous loci of wheat benzoxazinone biosynthetic
      genes TaBx3 and TaBx4 and characterization of their promoter sequences.
AB  - Common wheat (2n=6x=42, genome formula AABBDD) accumulates benzoxazinones (Bxs)
      as defensive compounds. There are five Bx biosynthetic genes (TaBx1-TaBx5), and
      their homoeologous alleles are located on all three homoeologous chromosomes of
      the A, B and D genomes. Here the molecular structures of the TaBx3 and TaBx4
      loci, both of which are located on chromosomes 5A, 5B and 5D, were revealed by
      sequencing transformation-competent artificial chromosome (TAC) clones. In all
      homoeologous chromosomes, TaBx3 existed downstream of TaBx4 in a tail-to-head
      manner, and the two genes were separated from each other by 9.0 kb in 5A, 7.3 kb
      in 5B and 11.3 kb in 5D. Among the three homoeologs of TaBx3 and TaBx4, the
      promoter sequences were less conserved than the coding sequences. The promoter
      sequences of TaBx3 and TaBx4 were highly similar to those of their respective
      orthologs in the diploid progenitors of common wheat, but were not similar to
      those of the maize orthologs. Sequence similarity was found between the TaBx3 and
      TaBx4 coding sequences, but not between their promoter sequences despite their
      similar transcription pattern at the seedling stage. Some putative cis-elements
      were found to be shared by all TaBx3 and TaBx4 promoter regions. These results
      imply that stage-specific transcription of TaBx3 and TaBx4 is not controlled by
      global sequence similarity of their promoters but by some essential cis-elements.
      The promoter activity measured by transient assays in wheat protoplasts was
      similar among the three homoeologs of TaBx3 and TaBx4 in spite of their
      differential transcript levels in wheat seedlings.

PMID- 18040658
TI  - Genetic mapping of clubroot resistance genes in oilseed rape.
AB  - Clubroot caused by the obligate biotrophic protist Plasmodiophora brassicae is a
      major disease of Brassica species. Clubroot resistances introduced from B.
      oleracea var. 'Bohmerwaldkohl' and resistance from B. rapa ECD-04 were
      genetically mapped in oilseed rape (B. napus L.). A doubled haploid (DH)
      population of rape seed was developed by crossing a resistant DH-line derived
      from a resynthesized B. napus with the susceptible cultivar 'Express'. The DH
      population was tested in the greenhouse against seven P. brassicae isolates
      showing low and high virulence toward B. oleracea or/and B. rapa. DH-lines with
      highest or lowest disease scores were used in a bulked segregant analysis (BSA),
      and 43 polymorphic AFLPs were identified. A genetic map of the whole genome was
      constructed using 338 AFLP and 156 anchored SSR markers. Nineteen QTL were
      detected on chromosomes N02, N03, N08, N13, N15, N16 and N19 giving resistance to
      seven different isolates. Race-specific effects were observed for all QTL, none
      of the QTL conferred resistance to all isolates. The phenotypic variance
      explained by the respective QTL ranged between 10.3 and 67.5%. All QTL could be
      assigned to both ancestral genomes of B. napus. In contrast to previous reports,
      a clear differentiation into major QTL from B. rapa and minor QTL from B.
      oleracea could not be found. Composite interval mapping confirmed the linkage
      relationships determined by BSA, thus demonstrating that markers for oligogenic
      traits can be selected by merely testing the distributional extremes of a
      segregating population.

PMID- 18040659
TI  - Replication of the association between variants in WFS1 and risk of type 2
      diabetes in European populations.
AB  - AIMS/HYPOTHESIS: Mutations at the gene encoding wolframin (WFS1) cause Wolfram
      syndrome, a rare neurological condition. Associations between single nucleotide
      polymorphisms (SNPs) at WFS1 and type 2 diabetes have recently been reported.
      Thus, our aim was to replicate those associations in a northern Swedish case
      control study of type 2 diabetes. We also performed a meta-analysis of published
      and previously unpublished data from Sweden, Finland and France, to obtain
      updated summary effect estimates. METHODS: Four WFS1 SNPs (rs10010131, rs6446482,
      rs752854 and rs734312 [H611R]) were genotyped in a type 2 diabetes case-control
      study (n = 1,296/1,412) of Swedish adults. Logistic regression was used to assess
      the association between each WFS1 SNP and type 2 diabetes, following adjustment
      for age, sex and BMI. We then performed a meta-analysis of 11 studies of type 2
      diabetes, comprising up to 14,139 patients and 16,109 controls, to obtain a
      summary effect estimate for the WFS1 variants. RESULTS: In the northern Swedish
      study, the minor allele at rs752854 was associated with reduced type 2 diabetes
      risk [odds ratio (OR) 0.85, 95% CI 0.75-0.96, p=0.010]. Borderline statistical
      associations were observed for the remaining SNPs. The meta-analysis of the four
      independent replication studies for SNP rs10010131 and correlated variants showed
      evidence for statistical association (OR 0.87, 95% CI 0.82-0.93, p=4.5 x 10(-5)).
      In an updated meta-analysis of all 11 studies, strong evidence of statistical
      association was also observed (OR 0.89, 95% CI 0.86-0.92; p=4.9 x 10(-11)).
      CONCLUSIONS/INTERPRETATION: In this study of WFS1 variants and type 2 diabetes
      risk, we have replicated the previously reported associations between SNPs at
      this locus and the risk of type 2 diabetes.

PMID- 18040660
TI  - Duration of breast-feeding and the incidence of type 2 diabetes mellitus in the
      Shanghai Women's Health Study.
AB  - AIMS/HYPOTHESIS: The aim of this study was to examine the association between
      lifetime breast-feeding and the incidence of type 2 diabetes mellitus in a large
      population-based cohort study of middle-aged women. METHODS: This was a
      prospective study of 62,095 middle-aged parous women in Shanghai, China, who had
      no prior history of type 2 diabetes mellitus, cancer or cardiovascular disease at
      study recruitment. Breast-feeding history, dietary intake, physical activity and
      anthropometric measurements were assessed by in-person interviews. The Cox
      regression model was employed to evaluate the association between breast-feeding
      and the risk of type 2 diabetes mellitus. RESULTS: After 4.6 years of follow-up,
      1,561 women were diagnosed with type 2 diabetes mellitus. Women who had breastfed
      their children tended to have a lower risk of diabetes mellitus than those who
      had never breastfed [relative risk (RR)=0.88; 95% CI, 0.76-1.02; p=0.08].
      Increasing duration of breast-feeding was associated with a reduced risk of type
      2 diabetes mellitus. The fully adjusted RRs for lifetime breast-feeding duration
      were 1.00, 0.88, 0.89, 0.88, 0.75 and 0.68 (p trend=0.01) for 0, >0 to 0.99,
      >0.99 to 1.99, >1.99 to 2.99, >2.99 to 3.99 and >or=4 years in analyses adjusted
      for age, daily energy intake, BMI, WHR, smoking, alcohol intake, physical
      activity, occupation, income level, education level, number of live births and
      presence of hypertension at baseline. CONCLUSIONS/INTERPRETATION: Breast-feeding
      may protect parous women from developing type 2 diabetes mellitus later in life.

PMID- 18040661
TI  - Mean blood glucose compared with HbA1c in the prediction of cardiovascular
      disease in patients with type 1 diabetes.
AB  - AIMS/HYPOTHESIS: It is not known whether mean blood glucose (MBG) predicts the
      risk of macrovascular complications in diabetes any differently from HbA1c. In
      this study we therefore analysed data from the Diabetes Control and Complications
      Trial (DCCT) to assess the relationship between MBG, HbA1c and glucose
      variability with regard to the risk of cardiovascular disease in patients with
      type 1 diabetes. METHODS: Pre- and postprandial seven-point glucose profiles were
      collected quarterly during the DCCT in 1441 individuals. The relationship between
      time to first cardiovascular event and MBG, HbA1c and daily SD of blood glucose
      was assessed by Cox regression after adjusting for the known risk factors of
      macrovascular disease and the treatment groups of the patients. RESULTS: Cox
      regression showed MBG to be predictive of a cardiovascular event (p=0.019), but
      not HbA1c (p=0.858). A rise of 1 mmol/l in MBG was associated with an 11% rise in
      cardiovascular risk. MBG remained highly predictive (p=0.015) even after
      adjustment for HbA1c values and glucose variability. CONCLUSIONS/INTERPRETATION:
      This study has shown that during the DCCT MBG was a better predictor of the
      macrovascular complications of type 1 diabetes than HbA1c. It indicates that the
      cardiovascular risk associated with hyperglycaemia appeared within the time
      period of the study and that blood glucose rather than HbA1c may be the preferred
      means of assessing this risk.

PMID- 18040662
TI  - Insulin therapy in the intensive care unit should be targeted to maintain blood
      glucose between 4.4 mmol/l and 6.1 mmol/l.

PMID- 18040663
TI  - Intensive insulin therapy improves endothelial function and microvascular
      reactivity in young people with type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Macrovascular disease is an important cause of the increased
      morbidity and mortality rates associated with type 1 diabetes, and this vascular
      impairment begins in childhood. The aim of this study was to determine whether
      introducing intensive diabetes management [intensive insulin therapy (IIT) and
      'Sweet Talk' text-messaging support] produces measurable improvements in
      endothelial function. METHODS: One hundred and twenty-six patients fulfilled the
      eligibility criteria (type 1 diabetes for >1 year; on conventional insulin
      therapy (CIT); aged between 8 and 18 years), of whom 92 enrolled. Patients were
      randomised to group 1, CIT only (n=28); group 2, CIT and Sweet Talk (n=33); or
      group 3, IIT and Sweet Talk (n=31). Vascular assessments (including measures of
      endothelial damage, activation, dysfunction and oxidative stress) and HbA1c were
      performed at baseline and repeated after 12 months of the study. RESULTS:
      Glycaemic control deteriorated in patients on CIT, but improved significantly in
      patients allocated to IIT (p=0.007). IIT was associated with significantly
      greater improvements in E-selectin (p<0.0001) than CIT (group 1, p=0.026 and
      group 2, p=0.053). Vascular responses to acetylcholine improved in patients on
      IIT (p=0.017), but not in patients receiving CIT. These changes were all
      independent of HbA1c level. CONCLUSIONS/INTERPRETATION: IIT appears to be
      associated with improvements in vascular markers, independently of changes in
      HbA1c, suggesting that IIT may confer vascular protection in addition to
      improving glycaemic control.

PMID- 18040664
TI  - Optimising islet engraftment is critical for successful clinical islet
      transplantation.
AB  - Clinical islet transplantation is currently being explored as a treatment for
      persons with type 1 diabetes and hypoglycaemia unawareness. Although 'proof-of
      principle' has been established in recent clinical studies, the procedure suffers
      from low efficacy. At the time of transplantation, the isolated islets are
      allowed to embolise the liver after injection in the portal vein, a procedure
      that is unique in the area of transplantation. A novel view on the engraftment of
      intraportally transplanted islets is presented that could explain the low
      efficacy of the procedure.

PMID- 18040665
TI  - Interactions between ethanol and cocaine, amphetamine, or MDMA in the rat:
      thermoregulatory and locomotor effects.
AB  - RATIONALE: (+/-)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is often taken
      recreationally with ethanol (EtOH). In rats, EtOH may potentiate MDMA-induced
      hyperactivity, but attenuate hyperthermia. OBJECTIVE: Experiment 1 compared the
      interactions between EtOH (1.5 g/kg) and MDMA (6.6 mg/kg) with EtOH + cocaine
      (COCA; 10 mg/kg) and EtOH + amphetamine (AMPH; 1 mg/kg) on locomotor activity and
      thermoregulation. Experiment 2 used a weaker dose of MDMA (3.3 mg/kg) and larger
      doses of COCA (20 mg/kg) and AMPH (2 mg/kg). MATERIALS AND METHODS: Drug
      treatments were administered on four occasions (2, 5, and 2 days apart,
      respectively; experiment 1) or two (2 days apart; experiment 2). RESULTS: All
      psychostimulants increased activity, and EtOH markedly increased the effect of
      MDMA. AMPH alone-related hyperactivity showed modest sensitization across
      treatment days, while MDMA + EtOH activity showed marked sensitization. AMPH,
      COCA, and MDMA induced hyperthermia of comparable amplitude (+1 to +1.5 degrees
      C). Co-treatment with EtOH and AMPH (1 mg/kg) or COCA (10 mg/kg) produced
      hypothermia greater than that produced by EtOH alone. Conversely, EtOH attenuated
      MDMA-related hyperthermia, an effect increasing across treatment days. These
      results demonstrate that the interaction between MDMA and EtOH may be different
      from the interaction between EtOH and AMPH or COCA. CONCLUSION: Because of
      potential health-related consequences of such polydrug misuse, it is worth
      identifying the mechanisms underlying these interactions, especially between EtOH
      and MDMA. Given the different affinity profiles of the three drugs for serotonin,
      dopamine, and norepinephrine transporters, our results appear compatible with the
      possibility of an important role of serotonin in at least the EtOH-induced
      potentiation of MDMA-induced hyperlocomotion.

PMID- 18040667
TI  - Retention characteristics of a new butylimidazolium-based stationary phase. Part
      II: anion exchange and partitioning.
AB  - A surface-confined ionic liquid (SCIL) and a commercial quaternary amine silica
      based stationary phase were characterized employing the linear solvation energy
      relationship (LSER) method in binary methanol/water mobile phases. The retention
      properties of the stationary phases were evaluated in terms of intermolecular
      interactions between 28 test solutes and the stationary phases. The comparison
      reveals a difference in the hydrophobic and hydrogen bond acceptance interaction
      properties between the two phases. The anion exchange retention mechanism of the
      SCIL phase was demonstrated using nucleotides. The utility of the SCIL phase in
      predicting logk (IL/water) values by chromatographic methods is also discussed.

PMID- 18040666
TI  - Age differences in the spontaneous acquisition of nicotine self-administration in
      male Wistar and Long-Evans rats.
AB  - RATIONALE: Epidemiological evidence suggests that adolescents may exhibit a
      unique susceptibility to the motivational effects of nicotine compared to adults.
      In contrast to the hypothesis of an enhanced vulnerability to nicotine during
      adolescence, we have observed that nicotine is less reinforcing in adolescent
      compared to adult rats using a progressive ratio reinforcement schedule in an
      operant self-administration procedure, although prior operant conditioning
      experience may have masked differences in initial sensitivity to nicotine.
      OBJECTIVES: This study examined the spontaneous acquisition of nicotine self
      administration in adolescent (postnatal day (PD) 31) and adult (PD87) male Wistar
      and Long-Evans rats. MATERIALS AND METHODS: Rats self-administered nicotine
      (0.015 or 0.03 mg/kg/infusion, i.v.) during 2-h operant conditioning sessions
      under fixed-ratio-1 (FR1) and FR3 reinforcement schedules for six sessions each.
      A subset of rats (adolescents: PD42, adults: PD98) underwent extinction of
      responding and nicotine priming-induced reinstatement (0.15 mg/kg, s.c.). In a
      separate group of rats, saccharin self-administration (0.1 ml of 0.2% w/v) was
      tested to determine the specificity of our findings with nicotine. RESULTS: A
      greater proportion of adult compared to adolescent rats acquired self
      administration of 0.015 mg/kg/infusion nicotine, but both age groups readily
      acquired self-administration of 0.03 mg/kg/infusion nicotine and saccharin. Age
      differences in extinction of responding for nicotine or saccharin depended upon
      strain, but priming-induced reinstatement was similar across age and strain.
      CONCLUSIONS: The current findings are consistent with those obtained under a more
      demanding progressive ratio reinforcement schedule and suggest that adolescents,
      compared to adults, may not be as sensitive to the reinforcing effects of
      nicotine.

PMID- 18040668
TI  - Effects of medial olivocochlear efferent stimulation on the activity of neurons
      in the auditory midbrain.
AB  - Medial olivocochlear (MOC) efferents are known to suppress spontaneous activity
      and sound-evoked responses of primary afferents by their actions on outer hair
      cells in the cochlea. This study investigated the effects of MOC activation on
      the responses of single neurons in the central nucleus of the inferior colliculus
      (CNIC) of anaesthetized guinea pigs. Extracellular responses of CNIC neurons to
      contralateral tones were recorded with and without MOC stimulation in normal
      animals and in animals acutely treated with gentamicin to eliminate peripheral
      effects of MOC activation. In normal animals, input-output functions of CNIC
      neurons showed a variety of changes. Some effects resembled qualitatively those
      reported for primary afferents. However, other effects were also observed,
      including an increase of firing rates at medium- to high-tone levels and in a
      small number of neurons (10%), an increase in spontaneous activity. In addition,
      larger threshold shifts and larger reductions of spontaneous firing rates were
      observed as compared to effects seen in the periphery. In gentamicin-treated
      animals, activation of MOC efferents did not produce any changes in the input
      output functions or spontaneous activity of CNIC neurons. This observation is
      consistent with the majority of MOC-induced changes in monaural responses in the
      CNIC being mediated by the actions of MOC terminals in the cochlea and resulting
      from the interplay between altered afferent input and central circuitry.

PMID- 18040670
TI  - Changes in cytochrome P450 side chain cleavage expression in the rat hippocampus
      after kainate injury.
AB  - Our previous study showed an increase in total cholesterol level of the
      hippocampus after kainate-induced injury, but whether this is further metabolized
      to neurosteroids is not known. The first step in neurosteroid biosynthesis is the
      conversion of cholesterol to pregnenolone by the enzyme cytochrome P450 side
      chain cleavage (P450scc). This study was carried out to elucidate the expression
      of this enzyme in the kainate-lesioned rat hippocampus. A net decrease in P450scc
      protein was detected in hippocampal homogenates by Western blots at 2 weeks post
      kainate injection (time of peak cholesterol concentration after kainate injury).
      Immunohistochemistry showed decreased labeling of the enzyme in neurons, but
      increased expression in a small number of astrocytes. The level of pregnenolone
      was also analyzed using a newly developed gas chromatography-mass spectrometry
      (GC-MS) method, optimized for the rat hippocampus. A non-significant tendency to
      a decrease in pregnenolone level was detected 2 weeks post-lesion. This is in
      contrast to a large increase in oxysterols in the lesioned hippocampus at this
      time (He et al. 2006). Together, they indicate that increased cholesterol in the
      kainate lesioned hippocampus is mostly metabolized to oxysterols, and not
      neurosteroids.

PMID- 18040669
TI  - Adenosine receptor ligands protect against a combination of apoptotic and
      necrotic cell death in cerebellar granule neurons.
AB  - Agonists at A(1) receptors and antagonists at A(2A) receptors are known to be
      neuroprotective against excitotoxicity. We set out to clarify the mechanisms
      involved by studying interactions between adenosine receptor ligands and
      endogenous glutamate in cultures of rat cerebellar granule neurons (CGNs).
      Glutamate and the selective agonist N-methyl-D: -aspartate (NMDA), applied to
      CGNs at 9 div (days in vitro), both induced cell death in a concentration
      dependent manner, which was attenuated by treatment with the NMDA receptor
      antagonists dizocilpine, D: -2-amino-5-phosphono-pentanoic acid (D: -AP5) or
      kynurenic acid (KYA), but not by the non-NMDA receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX). Glutamate toxicity was reduced in the presence
      of all of the following: cyclosporin A (CsA), a blocker of the membrane
      permeability transition pore, the caspase-3 inhibitor, benzyloxycarbonyl-Asp(OMe)
      Glu(OMe)-Val-Asp(OMe)-fluoromethylketone (Z-DEVD-fmk), the poly (ADP-ribose)
      polymerase (PARP-1) inhibitor 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)
      isoquinolinone (DPQ), and nicotinamide. This is indicative of involvement of both
      apoptotic and necrotic processes. The A(1) receptor agonist, N (6)
      cyclopentyladenosine (CPA), and the A(2A) receptor antagonist 4-(2-[7-amino-2-[2
      furyl][1,2,4]triazolo[2,3-a][1,3,5]triazo-5-yl-amino]ethyl)phenol (ZM241385)
      afforded significant protection, while the A(1) receptor blocker 8-cyclopentyl
      1,3-dipropylxanthine (DPCPX) and the A(2A) receptor agonist 2-p-(2
      carboxyethyl)phenethylamino-5'-N-ethylcarboxyamidoadenosine (CGS21680) had no
      effect. These results confirm that glutamate-induced neurotoxicity in CGNs is
      mainly via the NMDA receptor, but show that a form of cell death which exhibits
      aspects of both apoptosis and necrosis is involved. The protective activity of
      A(1) receptor activation or A(2A) receptor blockade occurs against this mixed
      profile of cell death, and appears not to involve the selective inhibition of
      classical apoptotic or necrotic cascades.

PMID- 18040671
TI  - The effect of age on task-related modulation of interhemispheric balance.
AB  - Normal aging is associated with less lateralised task-related activation of the
      primary motor cortices. It has been hypothesized, but not tested, that this
      phenomenon is mediated transcallosaly. We have used Transcranial Magnetic
      Stimulation to look for age-related changes in interhemispheric inhibition (IHI).
      Thirty healthy individuals (aged 19-78 years) were studied using a paired-pulse
      protocol at rest and during a low-strength isometric contraction with the right
      hand. The IHI targeting the right motor cortex was assessed at two intervals, 10
      ms (IHI10) and 40 ms (IHI40). The corticospinal excitability of the left
      hemisphere was assessed by means of input-output curves constructed during
      voluntary construction. Age was not correlated with IHI10 or IHI40 at rest.
      During muscle contraction IHI tended to increase at both intervals. However, this
      increase in IHI during the active condition (changeIHI) was less evident with
      advancing age for the 40 ms interval (r = 0.444, P = 0.02); in fact a degree of
      disinhibition was often present. There was no correlation between age and
      changeIHI10. Age was negatively correlated with the area under the recruitment
      curve (r = -0.585, P = 0.001) and the size of the maximum MEP collected (r = 
      0.485, P = 0.007). ChangeIHI and measures of corticospinal excitability were not
      intercorrelated. In conclusion, task-related increases in interhemispheric
      inhibition seem to diminish with advancing age. This phenomenon is specific for
      long-latency IHI and may underlie the age-related bihemispheric activation seen
      in functional imaging studies. The mechanism underlying changes in IHI with
      advancing age and the association with changes in corticospinal excitability need
      further investigation.

PMID- 18040672
TI  - Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil.
AB  - OBJECTIVE: The aim of this study was to systematically investigate the mutual
      pharmacokinetic interactions in healthy volunteers between sildenafil, a
      phosphodiesterase-5 inhibitor, and bosentan, a dual endothelin receptor
      antagonist, both approved for treating pulmonary arterial hypertension (PAH).
      METHODS: A randomised, double-blind, placebo-controlled, parallel-group study
      with three treatment arms (sildenafil plus placebo, bosentan plus placebo and
      sildenafil plus bosentan) was conducted in 55 healthy male volunteers (51
      completers). Study duration was 18 days per treatment group. Sildenafil was
      administered three times daily on Days 1-6 and 11-16 (20 mg initially, increased
      to 80 mg after 3 days), and bosentan (125 mg) was administered twice daily on
      Days 7-17. RESULTS: On Day 16, bosentan decreased the maximum plasma
      concentration of sildenafil (c)(max)) by 55.4% [90% confidence interval (CI) 40.3
      66.6%] and the area under the plasma concentration versus time curve over a
      dosing interval (AUC(tau)) by 62.6% (90% CI 56.8-67.7%). Sildenafil increased
      bosentan C(max) by 42.0% (90% CI 15.4-74.8%) and (AUC(tau)) by 49.8% (90% CI 28.7
      74.5%). Bosentan and sildenafil in combination were well tolerated, with no
      serious adverse events reported. All adverse events were of mild or moderate
      intensity. CONCLUSIONS: In healthy volunteers, there is a mutual pharmacokinetic
      interaction between bosentan and sildenafil that may influence the dosage of each
      drug in a combination treatment. The clinical implications of combination therapy
      with bosentan and sildenafil are as yet unknown, and further trials in patients
      with PAH are needed.

PMID- 18040673
TI  - Perfusion-CT for early assessment of traumatic cerebral contusions.
AB  - INTRODUCTION: To investigate the value of perfusion-CT (PCT) for assessment of
      traumatic cerebral contusions (TCC) and to compare the abilities of early
      noncontrast CT and PCT modalities to evaluate tissue viability. METHODS: PCT
      studies performed in 30 patients suffering from TCC during the acute phase of
      their illness were retrospectively reviewed. Cerebral blood flow (CBF), volume
      (CBV) and mean transit time (MTT) were measured in three different areas: the
      hemorrhagic core of the TCC, the surrounding hypodense area and the perilesional
      normal-appearing parenchyma. TCC area was measured on CBF-, CBV- and MTT-derived
      maps and compared with the areas measured using the same slice obtained with CT
      scans performed on admission, at the time of PCT (follow-up CT) and at 1 week.
      RESULTS: TCC were characterized by low CBF and CBV values (9.2+/-6.6 ml/100 g per
      min and 0.9+/-0.7 ml/100 g, respectively) and a significant prolongation of MTT
      (11.9+/-10.7 s) in the hemorrhagic core whereas PCT parameters were more variable
      in the hypodense area. The TCC whole area showed a noticeable growth of the
      lesions during the first week of admission. In comparison with early noncontrast
      CT, CBV and CBF maps proved to be more congruent with the findings of noncontrast
      CT scans at 1 week. CONCLUSION: PCT confirmed the results of xenon-CT studies and
      was shown to allow better evaluation of tissue viability than noncontrast CT.
      These findings suggest that PCT could be implemented in the future for the early
      assessment of patients with traumatic brain injury.

PMID- 18040674
TI  - Diffusion tensor tractography of the lower spinal cord.
AB  - INTRODUCTION: We employed a diffusion-tensor (DT) imaging technique involving a
      single-shot echo-planar sequence in combination with parallel imaging for
      tractography of the lower spinal cord and assessed the feasibility of this
      technique. METHODS: Images were obtained at 1.5 T using a five-channel receiver
      coil. We used a single-shot echo-planar sequence with parallel imaging to acquire
      diffusion-weighted (DW) images in the axial plane with phase encoding in the
      right-left direction. A motion-probing gradient was applied in six directions
      with a b-value of 1,000 s/mm(2). The scan time was 5 min 15 s. On a reconstructed
      DW image in the sagittal plane, the spinal cord was included in a single region
      of-interest to generate a tractogram of the entire cord in seven volunteers and
      nine patients with spinal canal stenosis or vertebral metastasis. RESULTS: In
      each subject, although the conus medullaris and cauda equina were continuously
      visualized, the cord was demonstrated as a bundle of tracts color-coded in the z
      axis. Nerve roots were depicted showing color-coding in the x- and y-axes. In the
      patient group, displacement of the cord was depicted showing changes in the color
      of the cord. Displacement of the proximal nerve roots was also depicted in the
      two patients with vertebral metastasis. CONCLUSION: DT imaging using parallel
      imaging shows potential as a method for routine tractography of the lower spinal
      cord.

PMID- 18040675
TI  - A traditional Chinese herbal antilithic formula, Wulingsan, effectively prevents
      the renal deposition of calcium oxalate crystal in ethylene glycol-fed rats.
AB  - We investigated the effects of a traditional Chinese herbal formula, Wulingsan
      (WLS), on renal stone prevention using an ethylene glycol-induced
      nephrocalcinosis rat model. Forty-one male Sprague-Dawley (SD) rats were divided
      into four groups. Group 1 (n=8) was the normal control; group 2 (n=11) served as
      the placebo group, and received a gastric gavage of starch and 0.75% ethylene
      glycol (EG) as a stone inducer; group 3 received EG and a low dose of WLS (375
      mg/kg); and group 4 received EG and a high dose of WLS (1,125 mg/kg). Baseline
      and final 24 h urine samples were collected individually; biochemical data of
      urine and serum were also obtained at the beginning and at the end of the
      experiment. After 4 weeks, animals were killed and kidneys were harvested. The
      kidney specimens were examined by polarized light microscopy and the crystal
      deposits were evaluated by a semi-quantitative scoring method using computer
      software (ImageScoring). The results revealed that the rats of placebo group
      gained the least significant body weight; in contrast, the rats of WLS-fed groups
      could effectively reverse it. The placebo group exhibited lower levels of free
      calcium (p=0.059) and significantly lower serum phosphorus (p=0.015) in urine
      than WLS-fed rats. Histological findings of kidneys revealed tubular destruction,
      damage and inflammatory reactions in the EG-water rats. The crystal deposit
      scores dropped significantly in the WLS groups, from 1.40 to 0.46 in the low-dose
      group and from 1.40 to 0.45 in the high-dose group. Overall, WLS effectively
      inhibited the deposition of calcium oxalate (CaOx) crystal and lowered the
      incidence of stones in rats (p=0.035). In conclusion, WLS significantly reduced
      the severity of calcium oxalate crystal deposits in rat kidneys, indicating that
      Wulingsan may be an effective antilithic herbal formula.

PMID- 18040676
TI  - Evaluation of postoperative pulmonary regurgitation after surgical repair of
      tetralogy of Fallot: comparison between Doppler echocardiography and MR velocity
      mapping.
AB  - BACKGROUND: Pulmonary regurgitation is a common finding in patients after
      correction of tetralogy of Fallot (TOF). Right ventricular impairment and even
      ventricular arrhythmia have been ascribed to pulmonary valve insufficiency (PI),
      which is therefore an important issue in follow-up examinations. OBJECTIVE: To
      compare PI measured by echocardiography (ECHO) with data provided by cardiac MRI
      (CMR). MATERIALS AND METHODS: We studied 54 selected patients (18 female; median
      age 14.0 years, range 3.8-53.4 years) after surgical correction of TOF. To
      quantify pulmonary regurgitant fraction (PRF) by CMR, flow velocity mapping was
      performed. On Doppler ECHO, length, width and localization of regurgitant flow
      was measured. The severity of PI was categorized as mild, moderate or severe and
      compared to the data obtained by CMR. RESULTS: On CMR the mean PRF was 29.2 +/-
      13.4%. Patients with a transannular patch had a significantly higher PRF (39.9 +/
      11.6%) than patients with an intact annular ring (23.6 +/- 11.4%).
      Differentiation by Doppler ECHO between the categories mild, moderate and severe
      PI was confirmed by significant differences in PRF measured by CMR (mild vs.
      moderate P < 0.04; moderate vs. severe P < 0.014; mild vs. severe P < 0.001).
      Furthermore, PRF correlated with right ventricular end diastolic volume index (r
      = 0.45, P < 0.01) and right ventricular end systolic volume index (r = 0.39, P <
      0.01). CONCLUSION: Doppler ECHO can estimate the severity of PI after repair of
      TOF with acceptable results compared to CMR flow measurement. In univariate
      analysis there is only a weak influence of PRF on right ventricular volume.

PMID- 18040677
TI  - Efficacy of percutaneous radiofrequency ablation of osteoid osteoma in children.
AB  - BACKGROUND: Percutaneous radiofrequency (RF) ablation of osteoid osteoma has high
      technical and clinical success rates. However, there are limited data on its use
      in the treatment of osteoid osteoma in children. OBJECTIVE: To assess the safety
      and efficacy of CT-guided percutaneous RF ablation of osteoid osteoma in children
      and compare the outcomes with published data on its use in patients unselected
      for age. MATERIALS AND METHODS: From January 2003 to July 2006, 23 children with
      osteoid osteoma were treated with CT-guided RF ablation using a straight rigid
      electrode. Their mean age was 11 years (range 3.5-16 years) and there were 15
      boys and 8 girls. The procedures were carried out under general anaesthesia.
      Follow-up was performed to assess technical and clinical outcome. The mean follow
      up period was 2.5 years (range 13-49 months). RESULTS: Technical success was
      achieved in 21 children (91.3%). Failure occurred in two children, in one due to
      failure to adequately localize the nidus within the dense sclerosis and in the
      other because of a short ablation time (2 min) because he developed hyperthermia.
      Clinical success was achieved in 18 patients within 2-5 days (primary clinical
      success rate 78.2%).These patients were allowed to fully weight-bear and function
      without limitation 1 week after the procedure. Pain recurrence was observed in
      two patients; one was treated successfully with a second ablation after 6 months
      (secondary clinical success rate 82.6%). Hyperthermia was observed in two
      patients during the procedure. Three other minor complications were observed:
      wound infection in one child and skin burn in two children. No major immediate or
      delayed complications were observed. CONCLUSION: Percutaneous CT-guided RF
      ablation is an effective and safe minimally invasive procedure for the treatment
      of osteoid osteoma in children. It has high technical and clinical success rates
      that are slightly lower than those of patients with a wider range of ages.

PMID- 18040679
TI  - EDTA-dependent assimilation of glucose and organic acids by an EDTA-degrading
      bacterium.
AB  - Bacterial strain VKM B-2445 is characterized by ethylenediaminetetraacetate
      (EDTA) requirement for cell growth. This strain could not grow on glucose and
      organic acids as the sole sources of carbon and energy, but it was able to
      metabolize these substrates added to EDTA medium. EDTA initiated assimilation of
      glucose, succinate, fumarate, malate, and citrate and supplied nitrogen for the
      biomass production from these substrates. Utilization of primarily nongrowth
      substrates by strain VKM B-2445 started when EDTA was exhausted or at least
      considerably degraded.

PMID- 18040678
TI  - The blood supply of early, late, and nonossifying cartilage: preliminary gray
      scale and Doppler assessment and their implications.
AB  - BACKGROUND: Comparative gray-scale Doppler US studies of various cartilages have
      not been reported before. OBJECTIVE: To study gray-scale US and perfusion
      patterns of different cartilages. MATERIALS AND METHODS: Three groups of
      cartilages were studied in 42 normal neonates. Group A included the proximal
      femoral chondroepiphysis of 20 neonates as well as proximal humeral, distal
      femoral, and proximal tibial epiphyses of 8 others. Group B included the patellar
      cartilage of nine neonates and group C included the rib cartilage of five
      neonates. RESULTS: Early ossifying cartilages all had numerous echogenic columns
      on US. Late ossifying patellar cartilage was amorphous and hypoechoic at birth
      but contained echogenic columns near the ossification age. Rib cartilage was
      hypoechoic and amorphous at all ages. The blood supply was detectable in all
      cartilages except the ribs. Peak systolic velocities increased with age in the
      proximal femoral epiphysis. The patellar cartilage was less vascular than the
      distal femoral epiphysis at birth, but more vascular at 14-24 months of age. The
      rib cartilage did not have any discernable blood supply at any age. CONCLUSIONS:
      Cartilage blood flow is detectable with current technology. Cartilage blood flow
      correlates with the timing of its ossification. Normal cartilage blood flow may
      prognosticate normality of its growth and development potential.

PMID- 18040680
TI  - Characterization of the superoxide dismutase SOD1 gene of Kluyveromyces marxianus
      L3 and improved production of SOD activity.
AB  - Superoxide dismutase (SOD) activity is one major defense line against oxidative
      stress for all of the aerobic organisms, and industrial production of this enzyme
      is highly demanded. The Cu/Zn superoxide dismutase gene (KmSOD1) of Kluyveromyces
      marxianus L3 was cloned and characterized. The deduced KmSod1p protein shares 86%
      and 71% of identity with Kluyveromyces lactis and Saccharomyces cerevisiae Sod1p,
      respectively. The characteristic motifs and the amino acid residues involved in
      coordinating copper and zinc and in enzymatic function were conserved. To the aim
      of developing a microbial production of Cu/Zn superoxide dismutase, we engineered
      the K. marxianus L3 strain with the multicopy plasmid YG-KmSOD1 harboring the
      KmSOD1 gene. The production of KmSOD1p in K. marxianus L3 and K. marxianus L3
      (pYG-KmSOD1) in response to different compositions of the culture medium was
      evaluated. The highest specific activity (472 U(SOD) mg(prot) (-1)) and the
      highest volumetric yield (8.8 x 10(5) U(SOD) l(-1)) were obtained by the
      recombinant strain overexpressing KmSOD1 in the presence of Cu(2+) and Zn(2+)
      supplements to the culture media. The best performing culture conditions were
      positively applied to a laboratory scale fed-batch process reaching a volumetric
      yield of 1.4 x 10(6) U(SOD) l(-1).

PMID- 18040681
TI  - Improvement in enzymatic desizing of starched cotton cloth using yeast
      codisplaying glucoamylase and cellulose-binding domain.
AB  - To utilize glucoamylase-displaying yeast cells for enzymatic desizing of starched
      cotton cloth, we constructed yeast strains that codisplayed Rhizopus oryzae
      glucoamylase and two kinds of Trichoderma reesei cellulose-binding domains (CBD1,
      CBD of cellobiohydrolase I (CBHI); and CBD2, CBD of cellobiohydrolase II
      (CBHII)). In this study, we aimed to obtain a high efficiency of enzymatic
      desizing of starched cotton cloth. Yeast cells that codisplayed glucoamylase and
      CBD had higher activity on starched cotton cloth than yeast cells that displayed
      only glucoamylase. Glucoamylase and double CBDs (CBD1 and CBD2) codisplaying
      yeast cells exhibited the highest activity ratio (4.36-fold), and glucoamylase
      and single CBD (CBD1 or CBD2) codisplaying yeast cells had higher relative
      activity ratios (2.78- and 2.99-fold, respectively) than glucoamylase single
      displaying cells. These results indicate that the glucoamylase activity of
      glucoamylase-displaying cells would be affected by the binding ability of CBD
      codisplayed on the cell surface to starched cotton cloth. These novel strains
      might play useful roles in the enzymatic desizing of starched cotton cloth in the
      textile industry.

PMID- 18040682
TI  - Microbial transformation of ginsenoside Rb(1) by Acremonium strictum.
AB  - Preparative-scale fermentation of ginsenoside Rb(1) (1) with Acremonium strictum
      AS 3.2058 gave three new compounds, 12beta-hydroxydammar-3-one-20 (S)-O-beta-D 
      glucopyranoside (7), 12beta, 25-dihydroxydammar-(E)-20(22)-ene-3-O-beta-D 
      glucopyranosyl-(1-->2)-beta-D -glucopyranoside (8), and 12beta, 20 (R), 25
      trihydroxydammar-3-O-beta-D -glucopyranosyl-(1-->2)-beta-D -glucopyranoside (9),
      along with five known compounds, ginsenoside Rd (2), gypenoside XVII (3),
      ginsenoside Rg(3) (4), ginsenoside F(2) (5), and compound K (6). The structural
      elucidation of these metabolites was based primarily on one- and two-dimensional
      nuclear magnetic resonance and high-resolution electron spray ionization mass
      spectra analyses. Among these compounds, 2-6 are also the metabolites of
      ginsenoside Rb(1) in mammals. This result demonstrated that microbial culture
      parallels mammalian metabolism; therefore, A. strictum might be a useful tool for
      generating mammalian metabolites of related analogs of ginsenosides for complete
      structural identification and for further use in pharmaceutical research in this
      series of compounds. In addition, the biotransformation kinetics was also
      investigated.

PMID- 18040683
TI  - Microbial production of L -glutamate and L -glutamine by recombinant
      Corynebacterium glutamicum harboring Vitreoscilla hemoglobin gene vgb.
AB  - Vitreoscilla hemoglobin (VHb) gene vgb equipped with a native promoter Pvgb or a
      tac promoter Ptac was introduced into Corynebacterium glutamicum ATCC14067,
      respectively. Ptac was proven to be more suitable for expressing VHb protein in
      higher concentration in both Escherichia coli and C. glutamicum strains compared
      with the native vgb promoter Pvgb. VHb-expressing C. glutamicum exhibited higher
      oxygen uptake rate and enhanced cell growth. Recombinant C. glutamicum harboring
      vgb gene equipped with Ptac promoter produced 23% more L -glutamate in shake
      flask culture and grew to 30% more cell density and formed 22% more L -glutamate
      in fermentor studies compared with the wild-type strain. When a site-directed
      mutagenesis in which Tyr405 was replaced by a phenylalanine residue (Y405F) was
      performed on glutamine synthesis gene, recombinant C. glutamicum overexpressing
      the mutated gene glnA' was able to produce L: -glutamine effectively. Co
      expression of vgb and glnA' genes in C. glutamicum produced 17 g/l L -glutamine
      in shake flask culture, approximately 30% more than that produced by the
      recombinant harboring only glnA' gene. In fermentor cultivation, the recombinant
      yielded 25% more cells and produced 40.5 g/l L -glutamine. In this study, it was
      clearly demonstrated that VHb significantly enhanced cell growth, L -glutamate,
      and L -glutamine production by recombinant C. glutamicum.

PMID- 18040684
TI  - Life-threatening acute pancreatitis due to thalidomide therapy for chronic graft
      versus-host disease.

PMID- 18040685
TI  - MPL 515 and JAK2 mutation analysis in MDS presenting with a platelet count of
      more than 500 x 10(9)/l.

PMID- 18040686
TI  - Pericardial effusion in a patient with acquired factor V inhibitor.

PMID- 18040687
TI  - Intraperitoneal gemcitabine pharmacokinetics: a pilot and pharmacokinetic study
      in patients with advanced adenocarcinoma of the pancreas.
AB  - BACKGROUND: The pyrimidine analogue gemcitabine (2', 2'-difluorodeoxycitidine,
      dFdC) is active against pancreatic cancer, and its high clearance (CL(tb)) and
      low incidence of local toxicity make it an excellent candidate for evaluation as
      intraperitoneal (IP) therapy. We designed a dosing schema that used multiple
      sequential exchanges of a peritoneal dialysate containing dFdC in an effort to
      produce prolonged IP dFdC exposure. METHODS: As part of a study involving multi
      modality therapy for advanced pancreatic adenocarcinoma, patients were treated
      with four 6-h IP dwells of dFdC (50 mg/m(2) in 2 l) over a 24-h period. A second
      24-h cycle of IP dFdC therapy was repeated 1 week later. Each exchange of
      dialysate contained 50 mg/m(2) dFdC in 2 l of commercial 1.5% dextrose dialysis
      solution. Plasma and peritoneal fluid were analyzed by HPLC to determine
      concentrations of dFdC and its inactive metabolite 2', 2' difluorodeoxyuridine
      (dFdU). Clinical data were recorded to note drug toxicity and response. RESULTS:
      Nine patients underwent IP dFdC therapy, and eight were able to receive two
      cycles. There were no recorded significant toxicities. Low plasma dFdC
      concentrations (<1 microg/ml) were present transiently in seven of nine patients,
      and dFdC was not detectable in the plasma of the other two. Plasma dFdU
      concentrations were low but increased gradually until 12 h and then declined
      little if any. IP dFdC concentrations declined rapidly, and dFdC was seldom
      measurable prior to administration of the next scheduled 6-h dwell. dFdU
      concentrations in peritoneal fluid were very low (<0.5 microg/ml) throughout
      treatment. The mean area under the concentration versus time curve (AUC) for dFdC
      in peritoneal fluid was 182 microg/ml x h, which was approximately 70x the AUC of
      dFdC reported in the ascites of a patient undergoing systemic dFdC therapy.
      CONCLUSIONS: IP dFdC was well tolerated, and no significant toxicities were
      noted. The rapid decrease in peritoneal dFdC concentrations and low
      concentrations of IP dFdU imply almost total absorption of IP-administered dFdC.
      Little, if any, dFdC could be detected in plasma, but the steady-state plasma
      dFdU concentrations also imply absorption and inactivation of virtually all IP
      administered dFdC. These findings are consistent with the known high CL(tb) and
      low incidence of local toxicity of dFdC and argue for its further evaluation as a
      drug for IP therapy.

PMID- 18040688
TI  - Identification of a minimal cre1 promoter sequence promoting glucose-dependent
      gene expression in the beta-lactam producer Acremonium chrysogenum.
AB  - The promoter of the cre1 gene, encoding the glucose-dependent regulator CRE1 from
      the beta-lactam producer Acremonium chrysogenum, carries 15 putative CRE1 binding
      sites (BS1 to BS15). For a detailed analysis, we fused cre1 promoter deletion
      derivatives with the DsRed reporter gene to perform a comparative gene expression
      analysis. Plate assays, Northern hybridizations, and spectrofluorometric
      measurements of DsRed identified the minimal D4 promoter sequence that promoted
      glucose-dependent expression. Truncated recombinant CRE1 interacted with D4 in
      electromobility shift analysis and these binding studies were further extended
      with two oligonucleotides, carrying putative CRE1 binding sites BS14 and BS15.
      Surface plasmon resonance analysis was performed using BS14 and BS15, along with
      four derivatives containing 2 or 4 bp substitutions within BS14 and BS15,
      respectively. Substitutions within BS14 abolished the high affinity interaction
      with CRE1, while mutations in BS15 only marginally diminished the affinity with
      CRE1. In vivo analysis of a modified D4 sequence with substitutions in the two
      binding sites confirmed the in vitro binding results and still promoted glucose
      dependent gene expression. Our results will contribute to the construction of
      versatile expression vectors carrying a minimal cre1 promoter sequence that still
      confers glucose-dependent induction of gene expression.

PMID- 18040689
TI  - Suppression of human macrophage interleukin-6 by a nonpsychoactive cannabinoid
      acid.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine which contributes to
      inflammation and tissue injury in several diseases. Thus, inhibition of IL-6
      production may be a useful strategy for treatment of patients with diseases such
      as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A synthetic
      nonpsychoactive cannabinoid, ajulemic acid (AjA), prevents joint damage in
      experimental arthritis. Results of experiments presented here indicate that
      addition of AjA (3-30 microM) to human monocyte derived macrophages in vitro
      reduces steady state levels of IL-6 mRNA and the subsequent secretion of IL-6
      from LPS stimulated cells. Although AjA binds to and activates PPARgamma, its
      anti IL-6 effects are PPARgamma independent. These studies provide evidence to
      support the view that AjA may prove to be an effective, safe antiinflammatory
      agent.

PMID- 18040692
TI  - Controlling recurrent papillary thyroid carcinoma in the neck by ultrasonography
      guided percutaneous ethanol injection.
AB  - The purpose of this study was to retrospectively evaluate the efficacy of
      ultrasonography-guided percutaneous ethanol injection (PEI) for neck recurrence
      of papillary thyroid carcinoma (NR-PTC). Twenty-seven patients (19-80 years old;
      mean, 53.2) with 47 NR-PTCs were treated by PEI and were followed-up (14-38
      months; mean, 28.2). Ethanol (99%) was repeatedly injected with adjusting needle
      position until the entire volume of NR-PTC was ablated. All patients received
      follow-up ultrasonography at 3-6-month intervals, and the percent volume decrease
      was measured. The NR-PTCs with decreased volume and no tumor vascularity on power
      Doppler study were regarded as treatment-effective. The NR-PTCs with stable or
      enlarged volume or with tumor vascularity were considered as treatment-failed, in
      which case PEI was repeated. The number of sessions and the total volume of
      ethanol per NR-PTC, and the volume of ethanol per session per NR-PTC were
      evaluated. All NR-PTCs significantly decreased in volume (range, 30-100%; mean,
      93.6%). The mean number of sessions, the total volume of ethanol per NR-PTC, and
      the mean volume of ethanol per session per NR-PTC were 2.1 sessions (range 1-6),
      2.4 ml (range 0.3-10.1), and 1.1 ml/session (range 0.3-3.0), respectively. PEI
      appears to be an alternative option for controlling NR-PTCs in the selected
      patients who are poor surgical candidates.

PMID- 18040691
TI  - High resolution computed tomography of the chest in cystic fibrosis (CF): is
      simplification of scoring systems feasible?
AB  - The purpose of this study was to simplify HRCT scoring systems (SS) for CF by
      selecting representative HRCT parameters. Forty-two consecutive patients with CF
      underwent baseline and follow-up chest HRCT. Three radiologists evaluated 84
      HRCTs employing five SS. "Simplified" HRCT SS were formed by selection of
      parameters exhibiting statistically significant relations with FEV1. Pulmonary
      function tests (PFTs) and nutrition (IBW%) were recorded. Regression analysis,
      Pearson correlation and T-test were used for statistical analysis. Three HRCT
      parameters were selected for the formation of "simplified" HRCT SS (severity of
      bronchiectasis, bronchial wall thickening, atelectasis-consolidation) using
      regression analysis. There was excellent correlation between each "simplified"
      and corresponding complete score (0.892 < r < 0.0967, p < 0.0001) or the
      remaining four complete scores (0.786 < r < 0.961, p < 0.0001). Strong
      correlation was found among the five "simplified" scores (0.803 < r < 0.997, p <
      0.0001). Comparing baseline complete and "simplified" scores with corresponding
      follow-up ones, significant worsening was observed (p < 0.0001). PFTs and IBW%
      did not change significantly. HRCT scores correlated moderately with FVC and
      FEV1, but there was no correlation with FEF25-75 and IBW%. "Simplified" HRCT SS
      are as reliable as the complete ones and detect progression of lung disease
      earlier than clinical parameters. They are easy to use and could be adopted in
      clinical practice.

PMID- 18040693
TI  - Bilateral ce-MR angiography of the hands at 3.0 T and 1.5 T: intraindividual
      comparison of quantitative and qualitative image parameters in healthy
      volunteers.
AB  - The purpose of this study was to determine the benefit of bilateral contrast
      enhanced MR angiography (ce-MRA) of the hands at 3.0 Tesla (T) compared with an
      established 1.5-T technique in healthy volunteers. Intraindividual bilateral ce
      MRA of the hands was performed at 1.5 T and 3.0 T in 14 healthy volunteers using
      a timed ultra-fast GRE sequence featuring parallel acquisition. The evaluation
      comprised measurement of the vessel signal-to-noise ratio (SNR) and contrast-to
      noise ratio (CNR), rating of the image quality and the assessment of artefacts
      and venous contamination. At 3.0 T, SNR improved up to 95% and CNR up to 129%.
      The image quality of the larger inflow arteries, the palm arches and common
      digital arteries was good or sufficient at either magnetic field strengths.
      However, 3.0-T MRA was clearly superior in the depiction of the digital arteries.
      Ce-MRA of the hand clearly profits from the use of 3.0 T. Compared with 1.5 T, a
      substantial increase of CNR is found resulting in a significantly better
      delineation of the small digital arteries. Saturation affects more the SNR of the
      perivascular tissue than the contrast-enhanced blood, and thus leads to a marked
      increase of CNR at 3.0.

PMID- 18040694
TI  - Long-term outcome of home dipstick testing for hematuria.
AB  - The most common symptom of bladder cancer (BC) is hematuria and microhematuria
      will occur in virtually all patients with BC if one tests for it frequently
      enough. However, hematuria even when caused by serious disease, often is
      intermittent, and once above some threshold the degree of microhematuria is
      unrelated to the seriousness of its underlying cause. Based on these principles a
      BC screening study was conducted to determine if repetitive hematuria testing can
      detect BC early and whether this resulted in reduced BC mortality, in long-term
      follow-up compared with disease related outcomes of a contemporary unscreened
      population similar to the one taking part in screening. The study and the long
      term outcomes are reviewed. At 14 years minimum follow-up, none of the 21 men
      diagnosed with BC by hematuria screening have died of the disease; 12 were still
      alive and 9 had died of diseases other than BC, with a median survival of 8.8
      years. The lower overall mortality in screenees with BC was primarily because of
      the reduced mortality from BC in that group. Screening had effected a shift of
      the high grade tumors to earlier (more superficial) stages at diagnosis.

PMID- 18040695
TI  - Three-dimensional computed tomography for detection of tracheobronchial foreign
      body aspiration in children.
AB  - Foreign body aspiration (FBA) into the tracheobronchial tree is a frequent and
      serious cause of respiratory problems in children. Chest X-ray (CXR) is often
      inaccurate in diagnosing FBA when the object is radiolucent. Three-dimensional
      computed tomography (CT) is a noninvasive technique that can detect the narrowing
      of the airway resulting from the presence of a foreign body. We conducted a
      retrospective study comparing the performance of CT scan and CXR in the diagnosis
      of FBA. Eleven patients (mean age 2.1 years) with a history suggestive of foreign
      body aspiration were examined by three-dimensional chest CT and CXR during the
      study. The presence of foreign bodies was confirmed and they were removed by
      rigid or flexible bronchoscopy under general anesthesia. Foreign body aspiration
      (FBA) was detected in all the 11 patients by CT scan (sensitivity, 100%), but CXR
      of three of the patients showed no evidence of FBA (sensitivity, 72.7%). The
      foreign bodies were located in the right main bronchus (n = 4), the left main
      bronchus (n = 5), and the trachea (n = 2). The mean length of hospital stay was
      3.8 days. In our study, three-dimensional chest CT scan was more sensitive than
      CXR in detecting the presence of aspirated foreign bodies in children. The
      superior sensitivity and short time required for CT should help to reduce delays
      in diagnosis. These benefits may prompt further studies to determine whether CT
      could be used to reduce the number of unnecessary bronchoscopies performed in
      children being evaluated for FBA.

PMID- 18040696
TI  - The effects of varicocele and its surgical correction on vas deferens motility.
AB  - Varicocele is the abnormal dilation of venous pampiniform plexus and internal
      spermatic vein. Its prevalence in the adolescent period is almost equal to the
      prevalence of adult age. That is why the disease is accepted to appear in early
      adolescence and does not disappear spontaneously. Varicocele is established to be
      the most common cause of infertility in the adulthood period in terms of the
      testicular and/or epididymal damages it causes. Besides, malfunctioning of testis
      and/or epididymis cannot be blamed as the one and only reason of infertility. One
      major reason of the male infertility is vas deferens motility disorders. There is
      limited data in the literature investigating the effects of varicocele on the vas
      deferens motility. The aim of the study is to evaluate not only the motility
      defects of vas deferens for the period of varicocele, but also the effects of
      surgical varicocele correction on vas deferens motility. Thirty male Wistar
      Albino rats were allocated to five groups. In the control group (Gr C, n = 6)
      bilateral vas deferens strips were harvested without any surgical intervention.
      Using the partial left renal vein obstruction technique, the experimental
      varicocele model was performed for the other four groups. Varicocele was apparent
      for these animals after the fourth week of the venous ligation. Bilateral vas
      deferens strips of varicocele group (Gr V, n = 6) were harvested. The rest of the
      animals having varicocele underwent relaparotomies. Three different surgical
      procedures were performed to these animals. The animals of group P (Gr P, n = 6)
      and group I (Gr I, n = 6) underwent Palomo and Ivanissevich procedures,
      respectively, for varicocele correction. And the animals of group S (Gr S, n = 6)
      underwent sham operation. After 4 weeks of relaparotomies, bilateral vas deferens
      strips of all three groups harvested. The electrical field stimulation (EFS)
      induced responses of all vas deferens strips as well as exogenous drug induced
      responses were recorded and analysed. The results of the study showed that the
      varicocele significantly inhibited the first phase of biphasic response of vas
      deferens in the ipsilateral side. However the correction of varicocele, free from
      surgical technique, ameliorated the affected first phase of EFS induced biphasic
      response in the ipsilateral side. The results of this study suggest that
      varicocele can be the reason of male infertility by not only causing testicular
      and/or epididymal damages but also triggering vas deferens motility defects. The
      correction of varicocele free from surgical technique may reverse the damaging of
      the vas deferens. Therefore when indicated surgical correction of varicocele is
      essential. It seems that varicocele surgery does not only prevent late term
      testicular and/or epididymal damages but also avoids vas deferens motility
      defects.

PMID- 18040698
TI  - Spinal cord tau pathology in cervical spondylotic myelopathy.
AB  - We conducted an immunohistochemical and ultrastructural examination of the spinal
      cords from 11 cases of cervical spondylotic myelopathy (CSM), together with those
      from 11 age- and sex-matched control subjects. Immunostaining with AT8 antibody
      revealed various numbers of tau-positive neuropil thread-like structures (NTSs),
      often demonstrating a conspicuous astrocytic foot-like perivascular or subpial
      arrangement, and glial cells with short and thick processes, so-called thorn
      shaped astrocytes (TSAs), in the affected cervical cords in 8 of the 11 CSM cases
      (73%). A number of tau-positive neuronal cytoplasmic pretangles/tangles were also
      found in the gray matter in all the CSM cases (100%). No such astrocytic or
      neuronal tau lesions were found in the control subjects. The tau deposited in the
      NTSs and TSAs was predominantly 4-repeat tau, whereas the neuronal cytoplasmic
      pretangles/tangles contained both 3-repeat and 4-repeat tau. Ultrastructurally,
      paired helical filaments about 20 nm wide, together with glial filaments, were
      detected occasionally in the astrocytic processes. In conclusion, the present
      findings indicate that astrocytic and neuronal tau lesions appear in the affected
      cervical cord during the disease process of CSM.

PMID- 18040697
TI  - Temporal and regional morphological differences as a consequence of FGF-2
      deficiency are mirrored in the myenteric proteome.
AB  - The enteric nervous system with its intricate network of neurons and glia shows a
      high plasticity, which not only changes during pre- and postnatal development,
      but also with disease or changing dietary habits. FGF as a potent neurotrophic
      factor in the central nervous system might also play a specific role for the ENS
      development, FGF-2 knockout and corresponding wild-type mice were histologically
      and functionally analyzed. FGF-2 knockout mice are viable and thrive normally and
      do apparently not display any obvious neurological deficit. Morphological
      differences were studied on whole mount preparations of muscle and submucous
      layer using either cuprolinic blue or immunohistochemical stainings for the
      neuronal marker PGP 9.5. Ussing-chamber and isometric muscle contraction
      experiments were performed on isolated gut wall, respectively muscle
      preparations. Intravital microscopy with GFP-transfected E. coli bacteria was
      used to investigate influences upon bacterial translocation. In additional
      experiments the protein pattern of the isolated myenteric plexus of knockout and
      wild-type mice were compared using 2D-DIGE technology. The morphometric analysis
      of the myenteric plexus revealed significant differences between FGF-2 knockout
      and wild-type animals, resulting in larger neurons in the knock out animals,
      embedded in less densely packed enteric ganglia. While muscle contractility
      appeared not to be affected, there was a significant difference in bacterial
      translocation as well as differences in basal chloride secretion to be seen. The
      observed morphological differences were reflected in the varying protein
      patterns, which were revealed by 2D-DIGE. A large number of differentially
      expressed proteins were found in both colonic and duodenal samples. FGF obviously
      influences the development of well established gastrointestinal functions by
      various means, thus leading to minor but significant deficiencies. Whether the
      revealed deficits in the mucous barrier are indebted to the morphological
      alterations in the ENS cannot yet be proved, but is very likely.

PMID- 18040699
TI  - Effects of hyperbaric oxygen therapy on rabbit skeletal muscle during extremity
      lengthening.
AB  - INTRODUCTION: Extremity lengthening through distraction osteogenesis is limited
      by the surrounding skeletal muscle and neurovascular structures rather than the
      bone itself. The purpose of this study is to evaluate the effects of hyperbaric
      oxygen therapy on skeletal muscle during distraction osteogenesis. MATERIALS AND
      METHODS: Twenty New Zealand white rabbits were randomly divided into two groups.
      Right tibia of all rabbits was distracted at a rate of 0.125 mm per 6 h (0.5
      mm/day) for 10 days with circular external fixator. Experimental group rabbits
      (N=10) underwent 2.5 ATA hyperbaric oxygen therapy for 2 h everyday for 20 days,
      control group rabbits (N=10) did not receive any corresponding treatment.
      Skeletal muscle perfusion was evaluated with scintigraphy before and after the
      distraction period. Serum CPK, LDH and AST levels were measured before and after
      the distraction period. All animals were killed on the 27th day. The right tibias
      of all animals were removed and tibialis posterior muscle was harvested for
      histopathologic and histomorphometric assessment with light and electron
      microscopy. RESULTS: Skeletal muscle perfusion was decreased in the control group
      in comparison with pre-distraction level (P=0.008). However, no significant
      decrease was observed in the experimental group (P=0.678). There were no
      statistical differences in serum CPK, LDH and AST levels between groups (P=0.340,
      P=0.077, P=0.796). The mean area of the muscle fibers was measured as 398.66+/
      9.16 micro2 in the experimental group and 349.44+/-5.76 micro2 in the control
      group (P=0.000) with light microscopy. Mild fibrosis was observed in connective
      tissue component of muscle tissue in control group. An average of 26 myofibrils
      (20-32) was counted in a 16-cm2 unit area in experimental group and 50 myofibrils
      (35-65) in the control group with electron microscopy. Enlargement in the
      sarcoplasmic reticulum, degenerative changes in nuclear cytoplasm and increase in
      myofibril diameter were observed in the control group, which was not observed in
      the experimental group CONCLUSION: Results of this study suggest that HBO
      treatment alleviates the detrimental effects of distraction on skeletal muscles
      and preserves its ultrastructure.

PMID- 18040700
TI  - Compartment syndrome of the foot: an experimental approach to pressure
      measurement and release.
AB  - INTRODUCTION: Using a cadaver model and multiple continuous compartment pressure
      measurement, we sought to determine the pressure distribution in different
      osseofascial spaces of the foot and determine the quickest and most effective
      technique of pressure release. MATERIALS AND METHODS: The compartment pressures
      were measured (in mmHg) in five different osseofascial spaces of each foot. In
      stepwise manner, warmed saline was injected only into the central compartment
      only. Three experimental approaches to fasciotomy were studied. RESULTS: We
      recognized a simultaneous exponential increase of all foot compartments in all
      experimental models. With a medial fasciotomy technique first, a flexor brevis
      compartment incision was necessary to release pressures in the central
      compartments. Following this procedure, pressure was released in the tarsal
      tunnel and in the intermetatarsal area immediately. Pressure reduction in the
      central flexor space and in the tarsal tunnel was less effective with a dorsal
      fasciotomy technique. CONCLUSIONS: There is no pressure increase of a "single"
      osseofascial space in case of a foot compartment syndrome. If immediate pressure
      release is required, a medial fasciotomy technique including the central flexors
      should be favoured.

PMID- 18040701
TI  - Segmental wire fixation for lumbar spondylolysis associated with spina bifida
      occulta.
AB  - INTRODUCTION: The effectiveness of segmental wire fixation technique in repairing
      lumbar spondylolysis has already been reported. However, whether the technique
      can be indicated for spondylolysis associated with spina bifida, which is
      occasionally found with spondylolysis, is not well known. In this study, the
      authors report the mid-term clinical outcome of the procedure performed in
      patients with symptomatic lumbar spondylolysis associated with spina bifida
      occulta. MATERIALS AND METHODS: Among 20 patients with symptomatic lumbar
      spondylolysis who underwent segmental wire fixation between 1996 and 2001, four
      patients associated with spina bifida occulta were evaluated with an average of
      32 months follow-up. Bony union at spondylolysis sites and spina bifida was
      evaluated using plain X-rays and computed tomography (CT) scans. Clinical
      symptoms were assessed using Japanese Orthopedic Association scores for back pain
      (JOA scores) and Henderson's evaluation of functional capacity. RESULTS: The
      radiographic examinations of the latest follow-ups revealed the following
      results. Pars defect; in three cases with bilateral defect, one case healed
      bilaterally and two healed only unilaterally. One case with unilateral defect
      healed. Spina bifida; two cases showed bony union and two showed no union. Of the
      four patients operated, two were rated excellent with the remaining two good
      according to Henderson's evaluation. The recovery rate of JOA score was averaged
      at 69.7 +/- 23.5%. No serious complications were noted. CONCLUSIONS: In four
      cases associated with lumbar spondylolysis and spina bifida, segmental wire
      fixation provided satisfactory clinical outcomes.

PMID- 18040702
TI  - Timing of thoracolomber spine stabilization in trauma patients; impact on
      neurological outcome and clinical course. A real prospective (rct) randomized
      controlled study.
AB  - OBJECTIVE: Optimal timing of stabilization for spinal injuries is discussed
      controversially. The goal of this study is to investigate the neurological
      recovery and its influencing factors in thoracolumbar spine fractures after
      surgical decompression and stabilization within 8 h of spinal cord injury versus
      surgery which is performed between 3 and 15 days. METHODS: Twenty-seven patients
      undergoing thoracolumbar stabilization with neurological deficit for an acute
      thoracolumbar spinal injury at the level of Th8-L2 vertebra at Selcuk University
      between March 2004 and December 2006 were recorded. Patients with neurological
      deficit and medically stable for surgery underwent immediate stabilization within
      8 h defined as group I (n = 12) and patients underwent operation in 3-15 days
      after thoracolumbar injury were defined as group II (n = 15). Patients were
      assessed for neurologic deficit and improvement as defined by the scoring system
      of American spinal injury association (ASIA). RESULTS: In spite of comparable
      demographic data, patients in group I had a significantly shorter overall
      hospital and intensive care unit stay and had lesser systemic complications such
      as pneumonia and also exhibited better neurological improvement than group II (p
      < 0.05). CONCLUSION: Early surgery may improve neurological recovery and decrease
      hospitalization time and also additional systemic complications in patients with
      thoracolumbar spinal cord injuries. Thus early stabilization of thoracolumbar
      spine fractures within 8 h after trauma appears to be favorable.

PMID- 18040703
TI  - No mid-term difference in mosaicplasty in previously treated versus previously
      untreated patients with osteochondral lesions of the talus.
AB  - INTRODUCTION: Osteochondral transplantations, albeit technically challenging,
      appear promising not only in knee joint lesions, but also in the treatment of
      talus lesions. We hypothesized that in patients suffering osteochondral lesions
      of the talus, favorable outcomes are obtained in patients undergoing primary
      mosaicplasty as compared to patients undergoing secondary mosaicplasty. MATERIALS
      AND METHODS: Over a 3-year period (1998-2001), 14 patients (six male, eight
      female, median age 22 years) were treated with an autologous osteochondral
      transplantation of the talus. Eight patients were previously untreated (group I).
      Six patients had previous ankle procedures, such as microfracturing (group II).
      The median follow-up was 24 months and 100% complete at 12 months. The functional
      outcome was evaluated at least at 6 weeks, 12 weeks, and 1 year after surgery
      using pain on a visual analog scale (VAS) and sports activity was recorded at 1
      year after surgery. In ten patients, magnetic resonance imaging (MRI) of the
      ankle was performed at 1 year after surgery (group I/II: 7/3). RESULTS: Overall
      ankle pain was decreased from 6.9 +/- 2.1 to 4.0 +/- 2.8 postoperatively. The
      mean knee pain for the donor knee was 2.6 +/- 2.4. We found no significant
      difference between the primary mosaicplasty group and the secondary mosaicplasty
      group with regard to pain. MRI scans of ten patients showed a complete
      incorporation of the osteochondral cylinders at 1 year after surgery. CONCLUSION:
      Favorable outcomes were obtained in patients undergoing primary mosaicplasty as
      compared to patients undergoing secondary mosaicplasty. We found no significant
      difference among patients with previous ankle surgery in contrast to those
      without, with a median 24-months follow-up.

PMID- 18040704
TI  - Proximal humeral fractures: what is semi-rigid? Biomechanical properties of semi
      rigid implants, a biomechanical cadaver based evaluation.
AB  - INTRODUCTION: Proximal humerus fractures remain challenging especially in the
      elderly. Biomechanical data put semi-rigid implants in favour of osteopenic or
      osteoporotic situation. Little surgical side damage is associated with a minimal
      invasive approach of these implants. The aim of this study was to evaluate the
      mechanical properties of three such implants. MATERIAL AND METHODS: Fresh frozen
      cadaver specimens were mounted as proposed by the distributors. Three different
      implants were used: LCP-PH (locking compression plate proximal humerus, Synthes,
      Austria), HB (humerus block, Synthes, Austria), and IMC (intramedullary claw,
      ITS, Austria). Subcapital fracture was simulated by resecting a 5 mm gap. All
      specimens were comparable in "B" (one), "M" (ineral) and "D" (ensity). Four load
      cases were tested: varus bending, medial shearing and axial torque. A cyclic test
      (1,000 cycles) was performed in the first load case (varus stress) for all three
      implants. RESULTS: The LCP-PH was the most rigid in all three load cases, always
      followed by the HB. The IMC was the most elastic device with almost immeasurable
      values in axial torque. In the cyclic setting, the load reduction of the HB
      followed by the LCP-PH was significantly better than that for the IMC.
      CONCLUSION: The differences in stiffness are varying tremendously. The IMC is the
      implant with the lowest stiffness in all load cases and the highest load
      reduction. New "semi-rigids" claim good clinical performance, yet prospective
      clinical studies have to prove this. It is unlikely that the IMC can maintain
      fracture reduction in fracture situations of complex nature (no ligamentotaxis).

PMID- 18040705
TI  - Pulp thumb defect reconstruction using a twin neurovascular island flaps: a case
      report.
AB  - In this report, we present the functional and cosmetic results of a case with
      complete loss of the thumb pulp for which the Chen and Noordhoof techniques has
      been chosen for reconstruction. A 33-year-old man, artisan, had his right thumb
      caught in a machine during the work, resulting in a degloving injury in the
      entire pulp of the distal phalanx of the thumb with all other digits of the right
      hand intact. The patient was a young man, in good health and non-smoker. He was
      involved in a heavy manual work for which an appropriate soft coverage of the
      distal thumb was desirable. A reconstruction of the thumb pulp with a twin
      neurovascular island flaps as described by Chen and Noordhoff was planned and
      performed the day after his admission to the hospital. The patient turned up to
      work at 10 weeks after surgery. After 2 years, we obtained a good aesthetic
      result, a sensitivity in the thumb and at the donor site comparable to the other
      hand and a complete recovery of normal function of the hand. In focal pulp loss
      of the thumb, the twin neurovascular island flaps suggested by Chen and Noordhoff
      could be an easy and efficient method to reconstruct soft tissue coverage and
      sensibility when microsurgical setting and abilities are not available.

PMID- 18040706
TI  - Cervical ectopic pregnancy after endometrial ablation: a case report.
AB  - CASE REPORT: A 44-year-old woman, with prior endometrial ablation, complaining of
      heavy vaginal bleeding was diagnosed with cervical ectopic pregnancy. Two doses
      of intramuscular methotrexate were administered as conservative treatment of the
      cervical pregnancy. Close follow-up in a dedicated early pregnancy unit allowed
      successful management on an outpatient basis. CONCLUSION: The urine pregnancy
      test maintains a crucial role in the investigation of abnormal vaginal bleeding
      in a sexually active patient. Conservative management of a cervical pregnancy can
      reduce the potential morbidity and mortality associated with the surgical
      treatment option.

PMID- 18040707
TI  - Multilocular intrauterine cystic mass, atypical presentation of endometrial
      stromal sarcoma: a case report.
AB  - Endometrial stromal sarcoma (ESS) is a rare neoplasm comprising only 0.2% of all
      uterine malignancies and 15-26% of primary uterine sarcomas. Pathology of the
      tumor was described as soft, fleshy, smooth polypoidal mass, which may protrude
      in the uterine cavity. This case report, represent atypical presentation of ESS
      as multilocular cystic intrauterine mass, which can be misdiagnosed as
      multilocular ovarian cyst.

PMID- 18040708
TI  - Preliminary evidence of the efficacy of probiotic eye-drop treatment in patients
      with vernal keratoconjunctivitis.
AB  - BACKGROUND: Probiotics have been shown to improve allergic inflammation. The aim
      of this study was to evaluate the efficacy of Lactobacillus Acidophilus eye-drops
      in controlling signs and symptoms of vernal keratoconjunctivitis (VKC). METHODS:
      Seven patients (mean age 11.8 +/- 4.3; five M, two F) with mild to moderate VKC
      were included in the study. Lactobacillus Acidophilus diluted in saline solution
      (2 x 10(8) CFU/ml) was administrated as eye-drops four times daily for 4 weeks in
      both eyes. Clinical signs (conjunctival hyperemia, chemosis, secretion, Trantas
      dots, superficial punctuate keratitis) and symptoms (itching, photophobia,
      burning, tearing) were evaluated and scored from 0 to 3 at baseline, after 2 and
      4 weeks of treatment. Total sign (TSS) and symptom (TSyS) scores were calculated.
      Conjunctival impression cytology was performed in three patients at baseline and
      after 4 weeks of treatment, in order to evaluate the expression of ICAM-1 and TLR
      4. RESULTS: In the six out of seven patients who completed the study, symptoms
      were significantly improved after both 2 weeks (TSyS: baseline 6.7 +/- 0.9 vs 4.1
      +/- 1.2; p = 0.017) and 4 weeks (TSyS: baseline 6.7 +/- 0.9 vs 3.6 +/- 1.2, p =
      0.011) of treatment. A significant improvement of clinical signs was observed
      after 4 weeks of treatment (TSS: baseline 7.5 +/- 1.6 vs 3.9 +/- 1.7, p = 0.034)
      but not after 2 weeks of treatment (TSS: baseline 7.5 +/- 1.6 vs 5.3 +/- 1.5;
      NS). In particular, photophobia was significantly reduced (2 +/- 0.6 vs 1 +/-
      0.3; p = 0.023) at 2 weeks, while at 4 weeks the scores for itching (1.8 +/- 0.3
      vs 1 +/- 0.3), tearing (1.6 +/- 0.4 vs 0.8 +/- 0.2), conjunctival hyperemia (2.3
      +/- 0.2 vs 1.4 +/- 0.5) and chemosis (1.2 +/- 0.4 vs 0.4 +/- 0.4) were
      significantly lower compared to baseline. A down-regulation of ICAM-1 and TLR-4
      was observed in two patients showing clinical improvement after 4 weeks of
      treatment. CONCLUSION: Our open pilot study showed that 1-month treatment with
      probiotic eye-drops improves signs and symptoms in patients with VKC. Additional
      double-blind controlled clinical trials with a larger sample of patients are
      needed to confirm the effects of topical Lactobacilli on VKC patients.

PMID- 18040709
TI  - Hormonal responses during a prolonged military field exercise with variable
      exercise intensity.
AB  - The purpose of the present study was to test the hypothesis that the magnitude of
      hormonal concentration alterations during a prolonged military field exercise
      with constant energy intake (EI) is influenced by changes in energy deficit (ED)
      induced by varying the exercise intensity. Basal serum hormone concentrations
      were measured in a group of healthy young male volunteers (n = 7) during a 20-day
      field exercise. During the first week of the exercise, the average ED was 4,000
      kcal/day (P-I), in the second week only 450 kcal/day (P-II), and in the last week
      1,000 kcal/day (P-III). During the first 5 days of the field exercise,
      significant increases in cortisol (COR, +32%) and growth hormone (GH, +616%)
      concentrations were observed, while insulin (INS, -70%), total testosterone (TES,
      -27%), free testosterone (TES(free), -26%) decreased. However, after these
      initial responses, COR and GH returned to the pre-exercise level by the beginning
      of P-II. Also TES and TES(free) recovered to the pre-exercise level by the
      beginning of P-III, and INS by the end of P-III. The concentration of TES (+29%)
      increased above the pre-exercise level by the beginning of P-III. Serum thyroxin
      (T(4)) concentration was significantly lesser (-12%) and urine urea concentration
      significantly higher (+78%) after the field exercise than before it. Therefore,
      it can be concluded that the lower levels of ED in the second and third phase (ED
      <1,000 kcal/day) allowed recovery of hormonal changes observed in the first phase
      with ED much greater than 1,000 kcal/day.

PMID- 18040710
TI  - Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation
      of L-type calcium currents in cultured neonatal cardiomyocytes.
AB  - Despite the fact that mineralocorticoid receptor (MR) antagonist drugs such as
      spironolactone and eplerenone reduce the mortality in heart failure patients,
      there is, thus far, no unambiguous demonstration of a functional role of MR in
      cardiac cells. The aim of this work was to investigate the activation pathway(s)
      mediating corticosteroid-induced up-regulation of cardiac calcium current (ICa).
      In this study, using neonatal cardiomyocytes from MR or glucocorticoid receptor
      (GR) knockout (KO) mice, we show that MR is essential for corticosteroid-induced
      up-regulation of ICa. This study provides the first direct and unequivocal
      evidence for MR function in the heart.

PMID- 18040711
TI  - Anionic derivatives of xyloglucan function as acceptor but not donor substrates
      for xyloglucan endotransglucosylase activity.
AB  - Tamarind xyloglucan was oxidised by reaction with sodium hypochlorite in the
      presence of 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (TEMPO). Galactose
      residues and non-xylosylated glucose residues were thus converted into
      galacturonic and glucuronic acid residues, respectively, producing an anionic
      polysaccharide. Acid hydrolysis of oxidised xyloglucan yielded two aldobiouronic
      acids, deduced to be beta-D: -GalpA-(1-->2)-D-Xyl and beta-D: -GlcpA-(1-->4)-D
      Glc. Anionic xyloglucan had a decreased ability to hydrogen-bond to cellulose and
      to complex with iodine. It was almost totally resistant to digestion by cellulase
      [endo-(1-->4)-beta-glucanase] and did not serve as a donor substrate for
      xyloglucan endotransglucosylase (XET) activity. Like several other anionic
      polysaccharides, it promoted XET activity when unmodified (non-ionic) xyloglucan
      was used as donor substrate. Anionic xyloglucan may mimic polyanions whose
      presence in the plant cell wall promotes the action of endogenous XTH proteins.
      NaOCl with TEMPO oxidised the heptasaccharide, XXXG, to form XXX-glucarate, which
      did serve as an acceptor substrate although at a rate approximately fourfold less
      than XXXG itself. Anionic derivatives of xyloglucan, acting as acceptor but not
      donor substrates, may be valuable tools for exploring the biological roles of
      XTHs in the integration versus the re-structuring of xyloglucan in the plant cell
      wall.

PMID- 18040712
TI  - Lymphangiogenesis in Crohn's disease: an immunohistochemical study using
      monoclonal antibody D2-40.
AB  - Crohn's disease (CD) is a chronic inflammatory bowel disorder of unknown
      etiology. An involvement of the intestinal lymphatic system has been suggested.
      Recently, monoclonal antibodies have become available to distinguish lymphatic
      vessels from blood vessels. The aim of the study was to examine the distribution
      of lymphatic vessels in ileal and colic walls of patients affected by CD and
      compare it with healthy controls and other inflammatory bowel diseases. Twenty
      eight cases of CD, 13 cases of other inflammatory bowel diseases, and 10 normal
      ileal and colic walls were studied. Immunohistochemical staining was performed
      using the monoclonal antibody D2-40. Quantification of lymphatic vessels was
      performed by identifying four fields with high density of lymphatics and then
      counting the number of lymphatic vessels at high resolution. Lymphatic diameter
      was also evaluated by using an ocular micrometer. Lymphatic vessels showed the
      highest density in CD specimens. The median number of lymphatics was
      significantly higher both in ileal and colic samples of CD than the other
      inflammatory diseases as well as normal controls. Moreover, in patients with CD,
      diffuse lymphangiectasia was also observed. The present data suggest that
      lymphangiogenesis and lymphangiectasia probably play a role in the pathogenesis
      of CD.

PMID- 18040713
TI  - MicroRNA: implications for cancer.
AB  - MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression post
      transcriptionally. After the discovery of the first miRNA in the roundworm
      Caenorhabditis elegans, these short regulatory RNAs have been found to be an
      abundant class of RNAs in plants, animals, and DNA viruses. About 3% of human
      genes encode for miRNAs, and up to 30% of human protein coding genes may be
      regulated by miRNAs. MicroRNAs play a key role in diverse biological processes,
      including development, cell proliferation, differentiation, and apoptosis.
      Accordingly, altered miRNA expression is likely to contribute to human disease,
      including cancer. This review will summarize the emerging knowledge of the
      connections between human miRNA biology and different aspects of carcinogenesis.
      Various techniques available to investigate miRNAs will also be discussed.

PMID- 18040714
TI  - Analysis of follicular lymphoma by dual-color fluorescence in situ hybridization.
AB  - Follicular lymphoma (FL) is divided into two groups: one with the
      t(14;18)(q32;q21) and the other without this translocation but with other
      chromosomal abnormalities including t(3q27) break. The majority of FLs in Western
      countries have the former chromosomal changes with characteristic clinical
      features and low histological grades. The goal of this study was to investigate
      the characteristics of Korean FLs with regard to the underlying molecular
      defects. Sixty-one cases of FL were evaluated from two centers in Korea by
      immunostaining for CD10, bcl-2, and bcl-6 proteins. Fluorescence in situ
      hybridization was performed to detect the t(14;18) and t(3q27) break. Cases with
      FL grade 3 accounted for 57% of all 61 cases. The t(14;18) was detected in 43.9%
      of the cases studied, and the frequency was 80, 50, 34.8, and 9.1% from grade 1
      through grade 3b. The t(3q27) was detected in 16.1% of cases. Cases without a
      t(14;18) were mainly histological grade 3 (P < 0.001) and had a tendency to have
      the t(3q27) and bcl-2 amplification. The incidence of t(14;18)-positive low-grade
      FL was found to be lower in Korea than in Western countries. The increased
      frequency of t(14;18)-negative grade 3 FL attributes to the lower incidence of
      t(14;18) in Korean FL.

PMID- 18040715
TI  - Involvement of Escherichia coli K1 ibeT in bacterial adhesion that is associated
      with the entry into human brain microvascular endothelial cells.
AB  - IbeT is a downstream gene of the invasion determinant ibeA in the chromosome of a
      clinical isolate of Escherichia coli K1 strain RS218 (serotype 018:K1:H7). Both
      ibeT and ibeA are in the same operon. Our previous mutagenesis and
      complementation studies suggested that ibeT may coordinately contribute to E.
      coli K1 invasion with ibeA. An isogenic in-frame deletion mutant of ibeT has been
      made by chromosomal gene replacement with a recombinant suicide vector carrying a
      fragment with an ibeT internal deletion. The characteristics of the mutant in
      meningitic E. coli infection were examined in vitro [cell culture of human brain
      microvascular endothelial cells (HBMEC)] and in vivo (infant rat model of E. coli
      meningitis) in comparison with the parent strain. The ibeT deletion mutant was
      significantly less adhesive and invasive than its parent strain E. coli E44 in
      vitro, and the adhesion- and invasion-deficient phenotypes of the mutant can be
      complemented by the ibeT gene. Recombinant IbeT protein is able to block E. coli
      E44 invasion of HBMEC. Furthermore, the ibeT deletion mutant is less capable of
      colonizing intestine and less virulent in bacterial translocation across the
      blood-brain barrier (BBB) than its parent E. coli E44 in vivo. These data suggest
      that ibeT-mediated E. coli K1 adhesion is associated with the bacterial invasion
      process.

PMID- 18040717
TI  - High performance thin layer chromatographic analysis of neutral lipids in the
      urine of BALB/c mice infected with Echinostoma caproni.
AB  - Silica gel high performance thin layer chromatography-densitometry was used to
      determine the neutral lipid profile in the urine of BALB/c mice experimentally
      infected with adults of Echinostoma caproni. An approximate 30 worm burden per
      host induced certain changes in the neutral lipid profile of the mice at 2 to 10
      weeks post-infection (PI) relative to the uninfected controls. Infection caused a
      significant increase (Student's t test, P < 0.05) in the methyl oleate fraction
      at 6 and 7 weeks PI relative to the uninfected controls. Neutral lipid profiles
      of urine may serve as an indicator of experimental infection of echinostomes in
      mice.

PMID- 18040716
TI  - A rare association of interrupted aortic arch type C and microdeletion 22q11.2.
AB  - Microdeletion 22q11.2 is associated with a variety of findings, and the most
      common are cardiac defects. It is very frequently associated with interrupted
      aortic arch (IAA) type B and very rarely with type A and type C. Here we report
      the first case of IAA type C associated with 22q11.2 deletion in Serbia and, to
      the best of our knowledge, the fourth case described worldwide so far. By this
      report we would like to point out that all patients with IAA type C who have
      additional features specific for 22q11.2 microdeletion syndrome should be
      screened for the presence of this deletion.

PMID- 18040718
TI  - Ascaridia numidae (Leiper, 1908; Travassos, 1913) in Rock Partridge (Alectoris
      chukar) in Turkey.
AB  - This report present first case of Ascaridia numidae isolated from three dead rock
      partridges (Alectoris chukar) with stressing morphological characteristics and
      its responsiveness to the medical treatment. A. numidae was confirmed by presence
      of one papilla on the posterior region of the preanal sucker and a total of 10
      pairs of the caudal papillae. In necropsy, a total of 680 (282 male and 3,988
      female) A. numidae and 289 (147 male and 142 female) Heterakis dispar were
      isolated from all partridges. Females were 11.20 mm longer and 0.22 mm wider than
      males. There was no difference in length of oesophagus (2.27 mm). Lengths of the
      spikules were equals and ranged from 2.08 to 2.93 according to the body size.
      Vulva was located in medial line and the mean egg size was 0.10 x 0.06 mm. Faecal
      samples from live birds from the same farm contained Ascaridia spp. and Heterakis
      spp. eggs. No eggs were encountered 1 week after oral administration of a single
      dose of levamisole (30 mg/kg), but 3 months post-medication. In conclusion, this
      is the first case reporting A. numidae in exotic birds in Turkey. A. numidae has
      unique papillae that are distinguishable from the other ascarids and is
      responsive to medical treatment as long as hygienic conditions are maintained.

PMID- 18040719
TI  - Experimental infection of Haemonchus contortus strains resistant and susceptible
      to benzimidazoles and the effect on mast cells distribution in the stomach of
      Mongolian gerbils (Meriones unguiculatus).
AB  - Establishment rate of Haemonchus contortus in non-suppressed and immunosuppressed
      gerbils within 14 days post-infection was compared after inoculation with 1,000
      third-stage larvae (L3), exsheathed BZ-susceptible larvae. Based on significantly
      higher number of larvae in gerbils receiving low doses of immunosuppressant agent
      hydrocortisone, development of benzimidazole (BZ)-susceptible and BZ-resistant
      strain of nematode in the stomach was studied on days 4, 7, 10, and 14 p.i.
      Sections of stomach from both groups of animals were examined for overall
      histopathological response and dynamics of mucosal mast cells (MMC) and
      connective tissue mast cells (CTMC). In the immunosuppressed gerbils, H.
      contortus L3 stage larvae developed to the L4 stage on days 10 and 14 p.i., and
      their sex ratio was higher toward female worms. Significantly higher ratios of
      establishment rate were recorded for BZ-susceptible than BZ-resistant strain.
      Infection elicited strong inflammation mainly in the lamina propria mucosae,
      where MMC numbers peaked on day 7 p.i., being present in a significantly higher
      numbers in gerbils infected with BZ-susceptible strain. Infection with BZ
      susceptible strain of nematode also resulted in a higher number of CTMC in
      comparison with the effect of BZ-resistant strain, which were observed in the
      tela submucosa only. Thus, H. contortus infection in gerbils seems to be a
      suitable model to study host-parasite interactions. Our results indicate that BZ
      resistant strain of H. contortus have a decreased capacity to establish infection
      in direct relation with lower mucosal and connective tissue MCs counts in the
      stomach.

PMID- 18040720
TI  - Infection of immunocompetent mice with acid-water-pretreated Cryptosporidium
      parvum results in weight loss, and intestinal (structural and physiological)
      alterations.
AB  - Cryptosporidiosis, caused by Cryptosporidium, causes self-limited diarrhea in
      normal hosts but may cause life-threatening diarrhea in immunocompromised
      persons. Cryptosporidium-induced manifestations, including weight-loss and
      intestinal physiological alterations are not noted in adult immunocompetent mice.
      So far, studies that have been used to test the therapeutic efficacy of drugs
      have been performed using various immunocompromised animal models. There is an
      urgent need of an immunocompetent small animal model that portrays
      Cryptosporidium-induced manifestations. In the current studies, we have compared
      two Cryptosporidium parvum pretreatment methods, we have hence used sodium
      hypochlorite or acidic water to treat Cryptosporidium parvum, followed by
      infection by oral gavage in adult immunocompetent C57BL6 mice. We demonstrated
      manifestations such as weight loss, intestinal structural and physiological
      alterations such as intestinal, villi blunting, and glucose malabsorption (as
      studied by the Ussing chamber technique) only in response to infection with C.
      parvum that has been treated with acidic water and not with sodium hypochlorite.
      These novel studies reveal that acidic water treatment of C. parvum results in
      manifestations of cryptosporidiosis in otherwise resistant immunocompetent mice.
      The current studies open up possibilities of using the normal immunocompetent
      mice model to test therapeutic drugs against cryptosporidiosis.

PMID- 18040721
TI  - Stem cells and neonatal brain injury.
AB  - Recent advances in regenerative medicine and in our understanding of neurogenesis
      may lead to new ways of recovering neuronal function lost or damaged during the
      perinatal period; such injuries are not amenable to conventional therapies. We
      review recent experimental studies based on immature rodental models of neonatal
      brain injury, especially hypoxic-ischemic encephalopathy. The developing brain is
      revealed to have considerable potential with respect to proliferation and
      migration to the injured site. However, the generation of fully differentiated
      neurons is extremely limited after brain injuries. Aggressive efforts to adjust
      the environment of the damaged brain in which tissue regeneration is occurring or
      more cautious stem cell transplantation will be required for the successful
      treatment of developmental brain injury.

PMID- 18040722
TI  - Characteristics of resident dendritic cells in various regions of rat periodontal
      ligament.
AB  - In the periodontal ligament (PDL) of normal rat molars, a considerable number of
      dendritic cells (DCs) are distributed as resident immunocompetent cells. We have
      hypothesized that the resident type of DCs can alter their morphology and
      phenotype to adapt to the microenvironment of the PDL. Thus, we have compared the
      characteristics of DCs in various regions of rat PDL by immunoelectron microscopy
      and gene expression analysis by means of reverse transcription/polymerase chain
      reaction. DCs in the periapical region show immature characteristics, i.e., small
      round profiles and few organelles. In the mesial region, which is the most stable
      area in the PDL, the density of DCs is the highest. DCs in the furcal region show
      the characteristics of activated antigen-presenting cells, i.e., CD86(high)
      expression, electron-dense lysosomes, and cell-to-cell contacts with lymphocytes.
      When the PDL is bacterially challenged by pulp exposure, the number of CD86+ DCs
      and contacts with lymphocytes increase in the furcal region. Gene expression
      analysis for the furcal region has also shown the up-regulation of the major
      histocompatibility complex class II alpha-chain, CD83, CD86, and the antigen
      presenting cell-lectin-like receptor A1. Thus, we have demonstrated heterogeneity
      in resident DCs. This may be associated with the difference in DCs regarding
      their state of maturation/activation, which may further reflect
      microenvironmental differences such as the amount of external antigens.

PMID- 18040723
TI  - Shifts in litterfall and dominant nitrogen sources after expansion of shrub
      thickets.
AB  - Woody encroachment into herbaceous ecosystems is emerging as an important
      ecological response to global change. A primary concern is alterations in C and N
      cycling and associated variations across a variety of ecosystems. We quantified
      seasonal variation in litterfall and litter N concentration in Morella cerifera
      shrub thickets to assess changes in litterfall and associated N input after shrub
      expansion on an Atlantic coast barrier island. We also used the natural abundance
      of (15)N to estimate the proportion of litterfall N originating from symbiotic N
      fixation. Litterfall for shrub thickets ranged from 8,991 +/- 247 to 3,810 +/-
      399 kg ha(-1) year(-1) and generally declined with increasing thicket age.
      Litterfall in three of the four thickets exceeded previous estimates of
      aboveground annual net primary production in adjacent grasslands by 300-400%.
      Leaf N concentration was also higher after shrub expansion and, coupled with low
      N resorption efficiency and high litterfall, resulted in a return of as much as
      169 kg N ha(-1) year(-1) to the soil. We estimated that approximately 70% of N
      returned to the soil was from symbiotic N fixation resulting in an ecosystem
      input of between 37 and 118 kg ha(-1) year(-1) of atmospheric N depending on
      site. Considering the extensive cover of shrub thickets on Virginia barrier
      islands, N fixation by shrubs is likely the largest single source of N to the
      system. The shift from grassland to shrub thicket on barrier islands results in a
      substantial increase in litterfall and foliar N concentration that will likely
      have a major impact on the size and cycling of ecosystem C and N pools.
      Increasing C and N availability in these nutrient-poor soils is likely to
      permanently reduce cover of native grasses and alter community structure by
      favoring species with greater N requirements.

PMID- 18040724
TI  - Influence of mass transfer limitations on the enzymatic synthesis of beta-lactam
      antibiotics catalyzed by penicillin G acylase immobilized on glioxil-agarose.
AB  - Mass transfer effects were investigated for the synthesis of ampicillin and
      amoxicillin, at pH 6.5 and 25 degrees C, catalyzed by penicillin G acylase
      immobilized on agarose. The influence of external mass transfer was analysed
      using different stirring rates, ranging form 200 to 800 rpm. Above 400 rpm, the
      film resistance may be neglected. Intra-particle diffusion limitation was
      investigated using biocatalysts prepared with different enzyme loads and agarose
      with different mean pore diameters. When agarose with 6, 8 and 10% of
      crosslinking were used, for the same enzyme load, substrates and products
      concentration profiles presented no expressive differences, suggesting pore
      diameter is not important parameter. An increase on enzyme load showed that when
      more than 90 IU of enzyme activity were used per mL of support, the system was
      influenced by intra-particle mass transfer. A reactive-diffusive model was used
      to estimate effective diffusivities of substrates and products.

PMID- 18040725
TI  - A case of aquaporin 2 R85X mutation in a boy with congenital nephrogenic diabetes
      insipidus.
AB  - Autosomal recessive nephrogenic diabetes insipidus (ARNDI) is a rare disease
      usually seen in patients with consanguineous parents. We report on a case of
      ARNDI in a patient with non-consanguineous parents who presented with recurrent
      febrile attacks. The differential diagnosis of ARNDI was made by desmopressin
      infusion test. A homozygous mutation, R85X, was detected in the aquaporin 2 gene
      (AQP2) of our patient, which has been described only once previously. This case
      is presented to stress that even male patients with non-consanguineous parents
      could have ARNDI with a AQP2 gene defect, and the desmopressin infusion test is
      useful for differential diagnosis.

PMID- 18040726
TI  - Acute renal failure in a 3-year-old child as part of the drug reaction with
      eosinophilia and systemic symptoms (DRESS) syndrome following hepatitis A.
AB  - We report on a 3-year-old Melanesian girl admitted for acute renal failure
      following subfulminant hepatitis A virus infection. While the child was slowly
      recovering from severe cytolytic hepatitis, she presented 8 weeks of protracted
      fever and major eosinophilia (30,000/microl); thereafter, acute renal failure
      (serum creatinine 295 micromol/l) occurred. Renal histology displayed diffuse
      eosinophilic infiltrate, with severe acute tubulointerstitial lesions associated
      with mild glomerular endocapillary proliferation and eosinophilic infiltrate,
      suggesting an immunoallergic mechanism. The child had received cefixime and
      cotrimoxazole 3 weeks prior to hospitalisation for the hepatitis A virus
      infection. The final diagnosis was of the syndrome drug reaction with
      eosinophilia and systemic symptoms or DRESS, induced by cefixime or cotrimoxazole
      and possibly triggered by the hepatitis A virus infection.

PMID- 18040727
TI  - Urinary interleukin-6 is useful in distinguishing between upper and lower urinary
      tract infections.
AB  - This study was designed to determine whether the measurement of interleukin (IL)
      6 in urine is useful for distinguishing between acute pyelonephritis and lower
      urinary tract infection. This observational study was carried out at Leon
      Hospital (Spain) on 35 patients (ten boys) aged between 0 and 14 years with
      urinary tract infection. Urinary levels of IL-6 were determined with enzyme
      linked immunosorbent assay (ELISA) at diagnosis and after recovery. Renal
      dimercaptosuccinate acid (DMSA) scan was performed on all patients to discard or
      confirm acute pyelonephritis. The mean urinary concentration [x +/- standard
      deviation (SD)] of IL-6 at diagnosis was 20.3 +/- 23.3 and 5.3 +/- 9.7 pg/ml in
      patients with acute pyelonephritis and lower urinary infection, respectively [95%
      confidence interval (CI): 2.6-27.4; p < 0.01]. Specificity for a value of IL-6
      >15 pg/ml, was 94.1% (95% CI: 91.1-97.1). Positive predictive value for IL-6 >15
      pg/ml was 87.5% (95% CI: 81.1-93.8). IL-6 was undetectable in the urine of both
      groups of patients at the time of recovery. Urinary levels of IL-6 are useful in
      differentiating between upper and lower urinary tract infection in children. In
      this clinical setting, a value >15 pg/ml is a strong indicator of acute
      pyelonephritis.

PMID- 18040728
TI  - Influence of type of luting cement used with all-ceramic crowns on load
      capability of post-restored endodontically treated maxillary central incisors.
AB  - Adhesive luting of the final restorations is supposed to support the overall
      strength of post-endodontically restored teeth. For evaluating adhesive vs
      conventional cementation, the load capability of adhesively restored
      endodontically treated teeth (ETT) with glass fibre-reinforced composite posts
      (GFRCP), resin composite cores and all-ceramic crowns was determined. Thirty-two
      caries-free human upper, central incisors were randomly assigned to four groups,
      endodontically treated and cut 2 mm above the cemento-enamel junction. All teeth
      were restored with GFRCP, composite core build-ups and all-ceramic crowns. All
      ceramic crowns were cemented with zinc phosphate cement (I), glass ionomer cement
      (II), and a self-adhesive resin cement (III and IV). After thermo-mechanical
      loading, the specimens were loaded to fracture. Maximum load capability F(max)
      and fracture patterns were compared using non-parametric statistics. Median
      values for the maximum load capability F(max) (minimum/maximum) in [N] were: I =
      503 (416/1,038), II = 442 (369/711), III = 502 (326/561) and IV = 518 (416/652).
      No statistically significant differences were found for F(max) (p = 0.761) and
      fracture patterns (p = 0.094) between the experimental groups. The type of
      cementation of all-ceramic crowns, whether self-adhesive or conventional, appears
      to have no impact on the load capability of ETT restored with GFRCP and composite
      core build-ups.

PMID- 18040729
TI  - In vitro and in vivo studies on the toxicity of dental resin components: a
      review.
AB  - In vitro and in vivo studies have clearly identified that some components of
      restorative composite resins, adhesives, and resin-modified glass ionomer cements
      are toxic. The mechanisms of cytotoxicity are related firstly to the short-term
      release of free monomers occurring during the monomer-polymer conversion.
      Secondly, long-term release of leachable substances is generated by erosion and
      degradation over time. In addition, ion release and proliferation of bacteria
      located at the interface between the restorative material and dental tissues are
      also implicated in the tissue response. Molecular mechanisms involve glutathione
      depletion and reactive oxygen species (ROS) production as key factors leading to
      pulp or gingival cell apoptosis. Experimental animal approaches substantiate the
      occurrence of allergic reactions. There is a large gap between the results
      published by research laboratories and clinical reports.

PMID- 18040730
TI  - Trichomonas vaginalis harboring Mycoplasma hominis increases cytopathogenicity in
      vitro.
AB  - The parasite Trichomonas vaginalis causes one of the most common non-viral
      sexually transmitted infections in humans. Mycoplasmas are frequently found with
      trichomonads but the consequences of this association are not yet known. In the
      present study, the effects of T. vaginalis harboring M. hominis on human vaginal
      epithelial cells and on MDCK cells are described. The results were analyzed by
      light, scanning and transmission electron microscopy, as well as using cell
      viability assays. There was an increase in the cytopathic effects on the
      epithelial cells infected with T. vaginalis associated with M. hominis compared
      to T. vaginalis alone. The epithelial cells exhibited an increase in the
      intercellular spaces, a lesser viability, and increased destruction provoked by
      the infected T. vaginalis. In addition, the trichomonads presented a higher
      amoeboid transformation rate and an intense phagocytic activity, characteristics
      of higher virulence behavior.

PMID- 18040731
TI  - Systemic air embolism after percutaneous transthorasic needle biopsy of the lung.
AB  - Computed tomography (CT)-guided percutaneous transthoracic biopsy of the lung is
      a well-established diagnostic technique, but it can pose complications to the
      patients. Air embolism is one of the rarest but potentially fatal complications
      of this procedure. The authors report a fatal case of systemic and massive air
      embolism to the coronary and cerebral arteries after the performance of lung
      biopsy. Careful reviewing of the obtained CT images during the procedure may
      avoid a missing systemic air embolism and can immediately provide an adequate
      therapy also in asymptomatic patients. This extremely rare complication is an
      inevitable event and may happen in spite of appropriate experience and meticulous
      care.

PMID- 18040732
TI  - Estimating material parameters of human skin in vivo.
AB  - An accurate mathematical representation of the mechanical behaviour of human skin
      is essential when simulating deformations occurring in the skin during body
      movements or clinical procedures. In this study constitutive stress-strain
      relationships based on experimental data from human skin in vivo were obtained. A
      series of multiaxial loading experiments were performed on the forearms of four
      age- and gender matched subjects. The tissue geometry, together with recorded
      displacements and boundary forces, were combined in an analysis using finite
      element modelling. A non-linear optimization technique was developed to estimate
      values for the material parameters of a previously published constitutive law,
      describing the stress-strain relationship as a non-linear anisotropic membrane.
      Ten sets of material parameters where estimated from the experiments, showing
      considerable differences in mechanical behaviour both between individual subjects
      as well as mirrored body locations on a single subject. The accuracy of
      applications that simulate large deformations of human skin could be improved by
      using the parameters found from the in vivo experiments as described in this
      study.

PMID- 18040733
TI  - Left ventricular function in patients with transposition of the great arteries
      operated with atrial switch.
AB  - In patients operated with atrial switch for transposition of the great arteries
      (TGA), the left ventricle (LV) supports the pulmonary circulation and is thus
      pressure unloaded. Evaluation of LV function in this setting is of importance, as
      LV functional abnormalities have been documented and might contribute to
      development of symptoms. The ventricular contraction pattern in 14 Senning
      operated TGA patients and 14 healthy controls was studied using tissue Doppler
      and magnetic resonance imaging. In the subpulmonary LV free wall, longitudinal
      strain was greater than circumferential strain (-23.6 +/- 3.6% vs. -19.1 +/-
      3.2%, p = 0.002) as in the normal right ventricle (RV) (-30.7 +/- 3.3% vs. -15.8
      +/- 1.3%, p < 0.001), but opposite to findings in the normal LV (-16.5 +/- 1.7%
      vs. -25.7 +/- 3.1%, p < 0.001). Subpulmonary strain and strain rate values were
      intermediate between those in the normal LV and RV. Ventricular free-wall torsion
      was reduced in the subpulmonary LV compared with both the normal LV (5.7 +/- 3.2
      degrees vs. 16.7 +/- 5.6 degrees , p < 0.001) and RV (5.7 +/- 3.2 degrees vs.
      11.4 +/- 2.6 degrees , p < 0.05). Furthermore, early diastolic filling of the
      subpulmonary LV differed from that of the normal LV. The subpulmonary LV
      displayed predominantly longitudinal shortening, as did its functional
      counterpart, the normal RV. However, the degree and rate of both longitudinal and
      circumferential shortening were intermediate between those of the normal LV and
      RV. This could represent a partial adaptation to the reduced pressure load.
      Decreased ventricular torsion and diastolic abnormalities might indicate
      subclinical ventricular dysfunction.

PMID- 18040735
TI  - A nomogram for predicting the degree of breast augmentation according to implant
      size.
AB  - Choosing the right implant size for a specific patient is a challenging aspect of
      breast augmentation. Bust circumference is obtained by measuring the chest
      circumference at the level of the nipple-areola complex. Pre- and postoperative
      bust circumference measurements obtained from 147 patients who underwent primary
      bilateral breast augmentation using round, textured, gel-filled implants were
      evaluated, and a practical reference list for future operations was developed.
      According to the results, each additional 100 ml in implant size yielded an
      approximate 2-cm increase in bust circumference. The authors believe these
      results gathered from systematic measurements may serve as a useful guide for
      choosing the right size implant for a satisfactory augmentation procedure.

PMID- 18040736
TI  - Habitat and biodiversity of on-farm water storages: a case study in Southeast
      Queensland, Australia.
AB  - On-farm water storages (locally known as farm dams or farm ponds) are an
      important part of many agricultural landscapes, as they provide a reliable source
      of water for irrigation and stock. Although these waterbodies are artificially
      constructed and morphologically simple, there is increasing interest in their
      potential role as habitat for native flora and fauna. In this article, we present
      results from a case study which examined the habitat characteristics (such as
      water physical and chemical parameters, benthic metabolism, and macrophyte cover)
      and the macrophyte and macroinvertebrate biodiversity of eight farm ponds on four
      properties in the Stanley Catchment, Southeast Queensland, Australia. Each
      landowner was interviewed to allow a comparison of the management of the ponds
      with measured habitat and biodiversity characteristics, and to understand
      landowners' motivations in making farm pond management decisions.The physical and
      chemical water characteristics of the study ponds were comparable to the limited
      number of Australian farm ponds described in published literature. Littoral zones
      supported forty-five macroinvertebrate families, with most belonging to the
      orders Hemiptera, Coleoptera, Odonata, and Diptera. Invertebrate community
      composition was strongly influenced by littoral zone macrophyte structure, with
      significant differences between ponds with high macrophyte cover compared to
      those with bare littoral zones. The importance of littoral zone macrophytes was
      also suggested by a significant positive relationship between invertebrate
      taxonomic richness and macrophyte cover.The landowners in this study demonstrated
      sound ecological knowledge of their farm ponds, but many had not previously
      acknowledged them as having high habitat value for native flora and fauna. If
      managed for aquatic organisms as well as reliable water sources, these artificial
      habitats may help to maintain regional biodiversity, particularly given the large
      number of farm ponds across the landscape.

PMID- 18040734
TI  - Intensive management affects composition of betaproteobacterial ammonia oxidizers
      in turfgrass systems.
AB  - Turfgrass is a highly managed ecosystem subject to frequent fertilization,
      mowing, irrigation, and application of pesticides. Turf management practices may
      create a perturbed environment for ammonia oxidizers, a key microbial group
      responsible for nitrification. To elucidate the long-term effects of turf
      management on these bacteria, we assessed the composition of betaproteobacterial
      ammonia oxidizers in a chronosequence of turfgrass systems (i.e., 1, 6, 23, and
      95 years old) and the adjacent native pines by using both 16S rRNA and amoA gene
      fragments specific to ammonia oxidizers. Based on the Shannon-Wiener diversity
      index of denaturing gradient gel electrophoresis patterns and the rarefaction
      curves of amoA clones, turf management did not change the relative diversity and
      richness of ammonia oxidizers in turf soils as compared to native pine soils.
      Ammonia oxidizers in turfgrass systems comprised a suite of phylogenetic clusters
      common to other terrestrial ecosystems. Nitrosospira clusters 0, 2, 3, and 4;
      Nitrosospira sp. Nsp65-like sequences; and Nitrosomonas clusters 6 and 7 were
      detected in the turfgrass chronosequence with Nitrosospira clusters 3 and 4 being
      dominant. However, both turf age and land change (pine to turf) effected minor
      changes in ammonia oxidizer composition. Nitrosospira cluster 0 was observed only
      in older turfgrass systems (i.e., 23 and 95 years old); fine-scale differences
      within Nitrosospira cluster 3 were seen between native pines and turf. Further
      investigations are needed to elucidate the ecological implications of the
      compositional differences.

PMID- 18040737
TI  - Systemic artery to pulmonary artery fistula associated with mitral regurgitation:
      successful treatment with endovascular embolization.
AB  - We present the case of a 60-year-old woman with symptomatic mitral regurgitation
      caused by a left-to-right shunt via anastomoses consisting of microfistulae, most
      likely of inflammatory origin, between the right subclavian artery and the right
      pulmonary artery. The three arteries responsible for fistulous formation,
      including the internal mammary, thyrocervical, and lateral thoracic arteries,
      were successfully occluded by transcatheter embolization using superabsorbent
      polymer microsphere (SAP-MS) particles combined with metallic coils. No
      complications have been identified following treatment with SAP-MS particles.
      This approach significantly reduced the patient's mitral regurgitation and she
      has remained asymptomatic for more than 4 years.

PMID- 18040738
TI  - Is the use of fullerene in photodynamic therapy effective for atherosclerosis?
AB  - The purpose of this study was to evaluate Fullerene as a therapeutic
      photosensitizer in the treatment of atherosclerosis. An atherosclerotic
      experimental rabbit model was prepared by causing intimal injury to bilateral
      external iliac arteries using balloon expansion. In four atherosclerotic rabbits
      and one normal rabbit, polyethylene glycol-modified Fullerene (Fullerene-PEG) was
      infused into the left external iliac artery and illuminated by light emitting
      diode (LED), while the right external iliac artery was only illuminated by LED.
      Two weeks later, the histological findings for each iliac artery were evaluated
      quantitatively and comparisons were made among atherosclerotic Fullerene+LED
      artery (n = 4), atherosclerotic light artery (n = 4), normal Fullerene+LED artery
      (n = 1), and normal light artery (n = 1). An additional two atherosclerotic
      rabbits were studied by fluorescence microscopy, after Fullerene-PEG-Cy5 complex
      infusion into the left external iliac artery, for evaluation of Fullerene-PEG
      incorporated within the atherosclerotic lesions. The degree of atherosclerosis in
      the atherosclerotic Fullerene+LED artery was significantly (p < 0.05) more severe
      than that in the atherosclerotic LED artery. No pathological change was observed
      in normal Fullerene+LED and LED arteries. In addition, strong accumulation of
      Fullerene-PEG-Cy5 complex within the plaque of the left iliac artery of the two
      rabbits was demonstrated, in contrast to no accumulation in the right iliac
      artery. We conclude that infusion of a high concentration of Fullerene-PEG
      followed by photo-illumination resulted not in a suppression of atherosclerosis
      but in a progression of atherosclerosis in experimental rabbit models. However,
      this intervention showed no adverse effects on the normal iliac artery.

PMID- 18040739
TI  - Transcatheter coil embolization of splenic artery aneurysm.
AB  - The purpose of this study was to evaluate clinical results and technical problems
      of transcatheter coil embolization for splenic artery aneurysm. Subjects were 16
      patients (8 men, 8 women; age range, 40-80 years) who underwent transcatheter
      embolization for splenic artery aneurysm (14 true aneurysms, 2 false aneurysms)
      at one of our hospitals during the period January 1997 through July 2005. Two
      aneurysms (12.5%) were diagnosed at the time of rupture. Multiple splenic
      aneurysms were found in seven patients. Aneurysms were classified by site as
      proximal (or strictly ostial) (n = 3), middle (n = 3), or hilar (n = 10). The
      indication for transcatheter arterial embolization was a false or true aneurysm
      20 mm in diameter. Embolic materials were fibered coils and interlocking
      detachable coils. Embolization was performed by the isolation technique, the
      packing technique, or both. Technically, all aneurysms were devascularized
      without severe complications. Embolized aneurysms were 6-40 mm in diameter (mean,
      25 mm). Overall, the primary technical success rate was 88% (14 of 16 patients).
      In the remaining 2 patients (12.5%), partial recanalization occurred, and re
      embolization was performed. The secondary technical success rate was 100%. Seven
      (44%) of the 16 study patients suffered partial splenic infarction. Intrasplenic
      branching originating from the aneurysm was observed in five patients. We
      conclude that transcatheter coil embolization should be the initial treatment of
      choice for splenic artery aneurysm.

PMID- 18040740
TI  - A review of the functionality of probiotics in the larviculture food chain.
AB  - During the past two decades, the use of probiotics as an alternative to the use
      of antibiotics has shown to be promising in aquaculture, particularly in fish and
      shellfish larviculture. This article reviews the studies on probiotics in
      larviculture, focusing on the current knowledge of their in vivo mechanisms of
      action. The article highlights that the in vivo mechanisms of action largely
      remain to be unravelled. Several methodologies are suggested for further in vivo
      research, including studies on gut microbiota composition, the use of gnotobiotic
      animals as test models, and the application of molecular techniques to study host
      microbe and microbe-microbe interactions.

PMID- 18040741
TI  - Purification and characterization of extracellular phytase from a marine yeast
      Kodamaea ohmeri BG3.
AB  - The extracellular phytase in the supernatant of cell culture of the marine yeast
      Kodamaea ohmeri BG3 was purified to homogeneity with a 7.2-fold increase in
      specific phytase activity as compared to that in the supernatant by ammonium
      sulfate fractionation, gel filtration chromatography (Sephadextrade mark G-75),
      and anion-exchange chromatography (DEAE Sepharose Fast Flow Anion-Exchange).
      According to the data from sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, the molecular mass of the purified enzyme was estimated to be
      98.2 kDa while the molecular mass of the purified enzyme was estimated to be 92.9
      kDa and the enzyme was shown to be a monomer according to the results of gel
      filtration chromatography. The optimal pH and temperature of the purified enzyme
      were 5.0 and 65 degrees C, respectively. The enzyme was stimulated by Mn(2+),
      Ca(2+), K(+), Li(+), Na(+), Ba(2+), Mg(2+) and Co(2+) (at a concentrations of 5.0
      mM), but it was inhibited by Cu(2+), Hg(2+), Fe(2+), Fe(3+), Ag(+), and Zn(2+)
      (at a concentration of 5.0 mM). The enzyme was also inhibited by
      phenylmethylsulfonyl fluoride (PMSF), iodoacetic acid (at a concentration of 1.0
      mM), and phenylgloxal hydrate (at a concentration of 5.0 mM), and not inhibited
      by EDTA and 1,10-phenanthroline (at concentrations of 1.0 mM and 5.0 mM). The K
      (m), V (max), and K (cat) values of the purified enzyme for phytate were 1.45 mM,
      0.083 micromol/ml . min, and 0.93 s(-1), respectively.

PMID- 18040742
TI  - A knowledge-anchored integrative image search and retrieval system.
AB  - Clinical data that may be used in a secondary capacity to support research
      activities are regularly stored in three significantly different formats: (1)
      structured, codified data elements; (2) semi-structured or unstructured narrative
      text; and (3) multi-modal images. In this manuscript, we will describe the design
      of a computational system that is intended to support the ontology-anchored query
      and integration of such data types from multiple source systems. Additional
      features of the described system include (1) the use of Grid services-based
      electronic data interchange models to enable the use of our system in multi-site
      settings and (2) the use of a software framework intended to address both
      potential security and patient confidentiality concerns that arise when
      transmitting or otherwise manipulating potentially privileged personal health
      information. We will frame our discussion within the specific experimental
      context of the concept-oriented query and integration of correlated structured
      data, narrative text, and images for cancer research.

PMID- 18040743
TI  - Specificity in chemical profiles of workers, brood and mutualistic fungi in Atta,
      Acromyrmex, and Sericomyrmex fungus-growing ants.
AB  - Neotropical attine ants live in obligatory symbiosis with a fungus that they grow
      for food on a substrate of primarily plant material harvested by workers.
      Nestmate recognition is likely based on chemical cues as in most other social
      insects, but recent studies have indicated that both the ants and their
      mutualistic fungi may contribute to the recognition templates. To investigate the
      within-colony variation in chemical profiles, we extracted and identified
      compounds from the cuticle of workers, the postpharyngeal gland of workers, ant
      pupae and larvae, and the fungal symbiont of three species of higher attine ants:
      Atta colombica, Acromyrmex echinatior, and Sericomyrmex amabilis. The relative
      proportions of identified compounds were compared and represented 11 classes: n
      alkanes, alkenes, branched methylalkanes, branched dimethylalkanes,
      trimethylalkanes, branched alkenes, aldehydes, alcohols, acetates, acids, and
      esters. The chemical profiles in all three species are likely to be sufficiently
      different to allow discrimination at the species and colony level and
      sufficiently similar within colonies to generate a relatively constant colony
      specific chemical gestalt. The relative likelihood of individual compounds being
      derived from the ants, the ant brood, or the fungal symbiont are discussed. We
      hypothesize that hydrocarbons are particularly important as recognition cues
      because they appear to simultaneously allow the assessment of developmental
      stages and the identification of symbiont, colony, and species.

PMID- 18040744
TI  - Hypertension management in minority communities: a clinician survey.
AB  - BACKGROUND: Rates of blood pressure (BP) control are lower in minority
      populations compared to whites. OBJECTIVE: As part of a project to decrease
      health-related disparities among ethnic groups, we sought to evaluate the
      knowledge, attitudes, and management practices of clinicians caring for
      hypertensive patients in a predominantly minority community. DESIGN/PARTICIPANTS:
      We developed clinical vignettes of hypertensive patients that varied by
      comorbidity (type II diabetes mellitus, chronic renal insufficiency, coronary
      artery disease, or isolated systolic hypertension alone). We randomly assigned
      patient characteristics, e.g., gender, age, race/ethnicity, to each vignette. We
      surveyed clinicians in ambulatory clinics of the 4 hospitals in East/Central
      Harlem, NY. MEASUREMENTS: The analysis used national guidelines to assess the
      appropriateness of clinicians' stated target BP levels. We also assessed
      clinicians' attitudes about the likelihood of each patient to achieve adequate BP
      control, adhere to medications, and return for follow-up. RESULTS: Clinicians'
      target BPs were within 2 mm Hg of the recommendations 9% of the time for renal
      disease patients, 86% for diabetes, 94% for isolated systolic hypertension, and
      99% for coronary disease. BP targets did not vary by patient or clinician
      characteristics. Clinicians rated African-American patients 8.4% (p = .004) less
      likely and non-English speaking Hispanic patients 8.1% (p = .051) less likely
      than white patients to achieve/maintain BP control. CONCLUSIONS: Clinicians
      demonstrated adequate knowledge of recommended BP targets, except for patients
      with renal disease. Clinicians did not vary management by patients'
      sociodemographics but thought African-American, non-English-speaking Hispanic and
      unemployed patients were less likely to achieve BP control than their white
      counterparts.

PMID- 18040745
TI  - Modified liver hanging maneuver to facilitate left hepatectomy and caudate lobe
      resection for hilar bile duct cancer.
AB  - The liver hanging maneuver (LHM) is a useful technique enabling a safe anterior
      approach, but it has several technical limitations for resection of the hepatic
      paracaval portion. We present a modified LHM that facilitates concurrent
      resection of the paracaval portion, a technique applicable to left liver
      resection for hilar bile duct (HBD) cancers. During 11 months from November 2006
      to September 2007, 10 HBD cancer patients underwent left liver resection using
      the modified LHM. This method included initial partial transection of the caudal
      paracaval portion. Thus, subsequent blind tunneling over the retrohepatic
      inferior vena cava can become as short as 2-3 cm in length, resulting in
      effective prevention of short hepatic vein injury. The parenchyma transection
      plane was tailored to remove most of the paracaval portion. This modified LHM
      technique was safely and effectively applied to 10 consecutive patients,
      requiring a shorter time than conventional dissection method for caudate lobe
      dissection. No significant bleeding occurred during retrohepatic tunneling. The
      final parenchymal transection plane after left liver resection using modified LHM
      was the same as that following the conventional surgical technique for HBD
      cancers. In conclusion, we think that this modified LHM is an effective,
      technically simple procedure for resection of the left liver and caudate lobe in
      HBD patients.

PMID- 18040746
TI  - Hepatic and splenic hydatidosis managed with percutaneous aspiration, injection,
      and reaspiration (PAIR) of the hepatic cyst and laparoscopic splenectomy.
AB  - The treatment of hydatidosis traditionally consisted of surgery with a
      perioperative course of anthelmintic medications. However, percutaneous
      aspiration, injection, and reaspiration (PAIR) combined with oral albendazole has
      been recently shown to be as effective as surgery in the treatment of liver
      hydatidosis. We report a 20-year-old female immigrant from Western Europe who
      presented with discomfort in her upper abdomen. Computed tomography revealed a
      5.7 x 7 x 5.9-cm cyst in segment 7 of the liver and a 17 x 15-cm cyst in the
      spleen in contiguity with the hilar vessels. Indirect hemaglutination test
      confirmed hydatidosis. A strategy with two different surgical approaches was
      designed to treat her condition: laparoscopic splenectomy and ultrasound-guided
      PAIR of the liver cyst. The patient was discharged on postoperative day 5, and at
      18 months follow-up, she is free of symptoms.

PMID- 18040747
TI  - Laparoscopic treatment of gastric GIST: report of 21 cases and literature's
      review.
AB  - BACKGROUND: Although the feasibility of laparoscopic resection of gastric
      gastrointestinal stromal tumors (GISTs) has been established, various aspects are
      debated. This paper describes the problems of minimally invasive resection of
      gastric GISTs and compares this experience with an extensive literature review.
      STUDY DESIGN: Between August 2001 and December 2006, 21 consecutive patients
      undergoing laparoscopic resection of gastric GISTs were enrolled in a prospective
      study. A literature review of laparoscopic treatment was performed on Pubmed
      using keywords GIST and surgery. A comparison with authors' experience with open
      wedge-segmental resection of GISTs (25 cases from November 1995 to December 2000)
      was also carried out. Statistical analysis was based on chi-squared test and t
      Student evaluation. RESULTS: Twenty-one patients, mean age 50.1 years (range, 34
      68 years), were submitted to laparoscopic wedge- segmental gastric resections.
      Mean tumor size was 4.5 cm (range, 2.0-8.5 cm). Mean operative time was 151 min
      (range, 52-310 min), the mean blood loss was 101 mL (range, 10-250 mL), and the
      mean hospital stay was 4.8 days (range 3-7 days). There were no major operative
      complications or mortalities. All lesions had negative resection margins. At a
      mean follow-up of 35 months, all patients were disease-free. Morbidity,
      mortality, length of stay, and oncologic outcomes were comparable to the open
      surgery retrospective evaluation (p=not significant). CONCLUSIONS: As found also
      in the literature review, the laparoscopic resection is safe and effective in
      treating gastric GISTs. Given these findings as well as the advantages afforded
      by laparoscopic surgery, a minimally invasive approach should be the preferred
      surgical treatment in patients with small- and medium-sized gastric GISTs.

PMID- 18040748
TI  - A better method for preventing infection of percutaneous endoscopic gastrostomy.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) has been widely used to
      maintain enteral nutrition in dysphagic patients. Local and occasional life
      threatening systemic infections are still the most common complications, and the
      major infection source may be nosocomial flora. The effect of antibiotic
      prophylaxis on reducing peristomal infection is popularly accepted. However, it
      is accompanied with a possible risk of increasing antibiotic resistance. AIM:
      This study attempted to determine whether 14-day discharge before PEG could
      reduce the rate of peristomal infection. MATERIALS AND METHODS: Fifty patients
      who had received PEG in our hospital were included in this study and followed for
      at least 6 months (except for those patients who died during this period).
      Patients were separated into two groups randomly. Twenty-five patients received
      PEG during in-hospitalization (group A). The other 25 patients received PEG until
      discharge at least for 14 days (group B). The most frequent indication for PEG
      insertion was the neurological condition. Risk factors for peristomal infection
      were analyzed statistically using logistic regression and expressed by odds
      ratios. Every possible factor was analyzed by chi-square test or Student's t
      test. RESULT: Our data showed that group A had a higher peristomal infection rate
      than group B (32 vs 8%) (p < 0.05). Group A also showed more need of antibiotics.
      The risk factors related to peristomal infection were group A and lower albumin.
      The total rate of 30-day mortality was 4%. DISCUSSION: When compared with
      previous data, our study showed a similar infection rate in group A, a lower
      infection rate in group B, and a lower 30-day mortality rate. This meant that one
      period of discharge could reduce the peristomal infections caused by colonized
      bacteria. It also decreased the need of using antibiotics and might avoid the
      possible adverse consequence of promoting bacterial resistance, which is an
      alarming and growing problem in hospital practice. CONCLUSION: We suggest that a
      14-day grace period after discharge, before PEG insertion, may decrease
      peristomal infection rate, length of hospital stay after PEG, and the need for
      antibiotics. This is suitable for moral and ethical considerations.

PMID- 18040750
TI  - Calculating surgical costs: how accurate and predictable is the cost of a
      laparoscopic Roux-en-Y gastric bypass?
AB  - BACKGROUND: Although bariatric surgery is highly effective for controlling
      obesity and its complications, it is uncovered by third-party payers in many
      countries. High cost and unpredictable expenses account for the lack of coverage.
      We developed at our obesity clinic a fixed package for the Laparoscopic Roux-en-Y
      Gastric Bypass (LRYGBP). The aim of this study is to evaluate the predictability
      and reproducibility of the estimated expenses in the first 150 consecutive
      patients who underwent LRYGBP as initial procedure. PATIENTS AND METHODS: A fixed
      package which included hospitalization, operative room expenses, medications,
      multidisciplinary support, and professional honorarium was established based on
      the experience gained with more than 500 preceding interventions. Actual direct
      medical costs of the initial 150 patients who underwent LRYGBP by one surgeon
      were analyzed and contrasted to the anticipated expenses. RESULTS: Mean age was
      35.8 +/- 11.8 years (range 16-69 years). Average body mass index (BMI) was 43.1
      +/- 4.8 kg/m(2) (range 35-70). Mean number of comorbidities per patient were 1.7
      +/- 0.8 (range 1-5). All patients completed a LRYGBP with no conversions. Mean
      hospital stay was 3 +/- 0.3 days. Complications occurred in 13 patients. Mean
      total expenses were 98.5 +/- 10% of the estimated costs. In 143 patients (95.3%),
      the total expenses were within 10% of the estimated costs, whereas in five they
      were > or =10% and in two > or =20%. CONCLUSION: Costs of a LRYGBP can be
      accurately predicted and are highly reproducible when interventions are performed
      by an experienced team and potentially lethal complications do not occur.

PMID- 18040749
TI  - Risk of malignancy in resected cystic tumors of the pancreas < or =3 cm in size:
      is it safe to observe asymptomatic patients? A multi-institutional report.
AB  - Recent international consensus guidelines propose that cystic pancreatic tumors
      less than 3 cm in size in asymptomatic patients with no radiographic features
      concerning for malignancy are safe to observe; however, there is little published
      data to support this recommendation. The purpose of this study was to determine
      the prevalence of malignancy in this group of patients using pancreatic resection
      databases from five high-volume pancreatic centers to assess the appropriateness
      of these guidelines. All pancreatic resections performed for cystic neoplasms <
      or =3 cm in size were evaluated over the time period of 1998-2006. One hundred
      sixty-six cases were identified, and the clinical, radiographic, and pathological
      data were reviewed. The correlation with age, gender, and symptoms (abdominal
      pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight
      loss, and anorexia), radiographic features suggestive of malignancy by either
      computed tomography, magnetic resonance imaging, or endoscopic ultrasound
      (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or
      common bile duct), and the presence of malignancy was assessed using univariate
      and multivariate analysis. Among the 166 pancreatic resections for cystic
      pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35
      mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1
      cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were
      malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in
      situ carcinomas arising in the setting of IPMN). A greater incidence of cystic
      neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of
      malignant pathology, with male patients having a higher incidence of malignancy
      (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was
      associated with malignancy (mean age 67 years in patients with malignant disease
      vs 62 years in patients with benign lesions (p < 0.05). A majority of the
      patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated
      with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and
      anorexia (p < 0.05). Radiographic features that correlated with malignancy were
      presence of a solid component (p < 0.0001), main pancreatic duct dilation (p =
      0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002).
      Twenty-seven of 31(87%) patients with malignant lesions had at least one
      radiographic feature concerning for malignancy. Forty-five patients (27%) were
      identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the
      patients in this group had benign disease. Of the patients that had no symptoms
      and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in
      situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in
      size was associated with older age, male gender, presence of symptoms (jaundice,
      weight loss, and anorexia), and presence of concerning radiographic features
      (solid component, main pancreatic duct dilation, common bile duct dilation, and
      lymphadenopathy). Among asymptomatic patients that displayed no discernable
      radiographic features suggestive of malignancy who underwent resection, the
      incidence of occult malignancy was 3.3%. This study suggests that a group of
      patients with small cystic pancreatic neoplasms who have low risk of malignancy
      can be identified, and selective resection of these lesions may be appropriate.

PMID- 18040751
TI  - Proximal duodenal-ileal end-to-side bypass with sleeve gastrectomy: proposed
      technique.
AB  - Proximal duodenal-ileal end-to-side bypass with sleeve gastrectomy is a new
      bariatric technique based on the biliopancreatic diversion with duodenal switch
      in which after the sleeve gastrectomy, the duodenum is anastomosed to the ileum
      in a Billroth-II fashion. A 200-cm common channel-alimentary limb is devised.
      Anticipating an appropriate weight loss, at least similar to that obtained after
      gastric bypass, theoretical benefits for operated patients are a shorter
      operative time, the performance of only one anastomosis, and no mesentery
      opening. A prospective trial is now being conducted to find out the results of
      the procedure and to compare them to those obtained with gastric bypass and
      standard duodenal switch.

PMID- 18040752
TI  - The ABC System: a simplified classification system for small bowel obstruction
      after laparoscopic Roux-en-Y gastric bypass.
AB  - Small bowel obstruction (SBO) after bariatric surgery is well documented.
      Although infrequent, it can be associated with considerable morbidity and
      mortality. The laparoscopic approach to Roux-en-Y gastric bypass (LRYGB) has
      gained widespread popularity for the treatment of morbid obesity since its first
      description in 1994. One of the theoretical advantages of a minimally invasive
      technique is reduced intraabdominal adhesions and, consequently, diminution in
      the incidence of SBO. However, the laparoscopic approach demonstrates a similar
      rate of obstruction to the open procedure. In this review, an electronic
      literature search was undertaken of Medline, Embase, and Cochrane databases for
      the period January 1990 to October 2006 on the history, presentation, clinical
      evaluation, preoperative diagnostic techniques, and management of SBO after LRYGB
      compared to the open approach.

PMID- 18040753
TI  - Polymorphism in the methylenetetrahydrofolate reductase (C677T) gene and
      homocysteine levels: a comparison in Brazilian patients with coronary arterial
      disease, ischemic stroke and peripheral arterial obstructive disease.
AB  - This study aimed to compare plasma levels of total homocysteine (tHcy) in
      different arterial events as well as to investigate an association between
      homocysteine levels and C677T polymorphism in Brazilian patients. A total of 145
      subjects were enrolled in this study including 43 patients with coronary arterial
      disease (CAD), 21 with ischemic stroke (IS), 44 with peripheral arterial
      obstructive disease (PAOD) and 37 control subjects. A preliminary analysis showed
      significant difference for tHcy plasma levels between patients with CAD (P =
      0.003) or PAOD (P = 0.03) compared to controls. However, after adjustment for
      sex, age, total cholesterol, LDL, diabetes, tabagism or C677T polymorphism, no
      significant differences were detected in tHcy levels among patients groups and
      controls. No significant correlation was demonstrated for C677T polymorphism and
      homocysteine levels. These results indicate that increased Hcy levels may not be
      considered an independent risk factor for atherothrombotic diseases in Brazilian
      patients.

PMID- 18040754
TI  - Preparation and mechanical characterization of a PNIPA hydrogel composite.
AB  - A poly (N-isopropylacrylamide) (PNIPA) hydrogel was synthesized by free radical
      polymerization and reinforced with a polyurethane foam to make a hydrogel
      composite. The temperature dependence of the elastic modulus of the PNIPA
      hydrogel and the composite due to volume phase transition was found using a
      uniaxial compression test, and the swelling property was investigated using an
      equilibrium swelling ratio experiment. The gel composite preserves the ability to
      undergo the volume phase transition and its elastic modulus has strong
      temperature dependence. The temperature dependence of the elastic modulus and
      swelling ratio of the gel composite were compared to the PNIPA hydrogel. Not
      surprisingly, the modulus and swelling ratio of the composite were less dramatic
      than in the gel.

PMID- 18040755
TI  - Dose-dependent effects of Ni (II) ions on production of three inflammatory
      cytokines (TNF-alpha, IL-1beta and IL-6), superoxide dismutase (SOD) and free
      radical NO by murine macrophage-like RAW264 cells with or without LPS
      stimulation.
AB  - The effect of Ni (II) ions on macrophages is not well understood. The purpose of
      this study was to examine the dose-dependent effects of Ni (II) ions up to 1,000
      micromol/L on production of three inflammatory cytokines (TNF-alpha, IL-1beta and
      IL-6), superoxide dismutase (SOD) and nitric oxide (NO) by murine macrophage-like
      RAW264 cells with (+) or without (-) lipopolysaccharide (LPS) -stimulation. Ni
      (II) ions caused LPS (-) RAW264 cells to slightly increase production of TNF
      alpha and IL-6, proportionally to the Ni (II) ion concentration while IL-1beta
      was not produced, and to slightly increase production of SOD and NO. It can be
      concluded that Ni (II) ions dose-dependently increased the inflammatory and
      oxidative stress conditions of LPS (-) RAW264 cells. LPS-stimulation caused
      RAW264 cells to produce in abundance the three inflammatory cytokines, SOD and
      NO. Ni (II) ions dose-dependently reduced the three cytokine quantities and NO
      amounts in LPS (+) RAW264 cells, while dose-independently increasing SOD amounts.
      It was noted that Ni (II) ions dose-dependently reduce the resistance power
      against bacteria of LPS (+) macrophages, because the production of volatile NO-
      bacteria killer is diminished proportionally to the Ni (II) ion concentration.

PMID- 18040756
TI  - Development, optimization and characterization of a full-thickness tissue
      engineered human oral mucosal model for biological assessment of dental
      biomaterials.
AB  - Restorative dental materials and oral health care products come into direct
      contact with oral mucosa and can cause adverse reactions. In order to obtain an
      accurate risk assessment, the in vitro test model must reflect the clinical
      situation as closely as possible. The aim of this study was to develop and
      optimize a three-dimensional full-thickness engineered human oral mucosal model,
      which can be used for biological assessment of dental materials. In this study
      human oral fibroblasts and keratinocytes were isolated from patients and seeded
      onto a number of collagen-based and synthetic scaffolds using a variety of cell
      seeding techniques and grown at the air/liquid interface to construct human oral
      mucosa equivalents. Suitability of 10 different scaffolds for engineering human
      oral mucosa was evaluated in terms of biocompatibility, biostability, porosity,
      and the ability to mimic normal human oral mucosa morphology. Finally an
      optimized full-thickness engineered human oral mucosa was developed and
      characterized using transmission electron microscopy and immunostaining. The oral
      mucosa reconstruct resembled native human oral mucosa and it has the potential to
      be used as an accurate and reproducible test model in mucotoxicity and
      biocompatibility evaluation of dental materials.

PMID- 18040757
TI  - The effect of PLGA sphere diameter on rabbit mesenchymal stem cells in adipose
      tissue engineering.
AB  - To investigate the effect of injectable PLGA sphere's diameter on adipose tissue
      engineering, rabbit mesenchymal stem cells were attached to various diameters of
      injectable PLGA spheres (<75; 75-100; 100-150; 150-200; and 200-250 microm).
      These five groups were cultured in adipogenic media for 2 weeks in vitro and
      injected into necks of nude mice. Prior to in vivo study, cell proliferation and
      adipogenic differentiation were determined by hexosaminidase assay and Oil red O
      staining after 2 weeks. Group C (100-150 microm) showed the highest adipogenic
      differentiation and the proliferation capacity of Group B (75-100 microm) was
      significantly higher than that of any other group. We harvested newly formed
      tissues from necks of nude mice after 1 and 4 weeks. Although PLGA spheres have
      not been degraded and there was no significant histological difference among
      various sizes of spheres after 1 week, well-organized fat pads (PLGA spheres were
      completely degraded) could be observed, and the histology of the 100-150 microm
      groups resembled that of native tissue after 4 weeks. Based on these experiments,
      we could conclude that the optimal size of PLGA spheres for adipogenesis was 100
      150 microm.

PMID- 18040758
TI  - In vitro evaluation of poly(caporlactone) grafted dextran (PGD) nanoparticles
      with cancer cell.
AB  - This study dealt with the preparation and characterization of coumarin-6 loaded
      poly(caprolactone) grafted dextran (PGD) nanoparticles (NPs) and evaluation of
      cellular uptake by using human gastric cancer cell line (SNU-638), in vitro. The
      potential application of these PGD NPs for sustained drug delivery was evaluated
      by the quantification and localization of the cellular uptake of fluorescent PGD
      NPs. Coumarin-6 loaded PGD NPs were prepared by a modified oil/water emulsion
      technique and characterized by various physico-chemical methods such as, laser
      light scattering for particle size and size distribution, atomic force microscopy
      (AFM), zeta-potential and spectrofluorometry to identify the release of
      fluorescent molecules from the NPs. SNU-638 was used to measure the cellular
      uptake of fluorescent PGD NPs. Confocal laser scanning microscopic images clearly
      showed the internalization of NPs by the SNU-638 cells. Cell viability was
      assessed by treating the SNU-638 cells with PGD NPs for 48 h. The results reveal,
      that these biodegradable polymeric NPs holds promise in biomedical field as a
      carrier.

PMID- 18040759
TI  - Protective effect of the natural product, chaetoglobosin K, on lindane- and
      dieldrin-induced changes in astroglia: identification of activated signaling
      pathways.
AB  - PURPOSE: The purpose of the present study was to identify the biochemical
      mechanism(s) of the preventative and reversal effects of Chaetoglobosin K (ChK),
      a bioactive natural product, on inhibition of gap junction-mediated communication
      and connexin phosphorylation by the tumor promoting organochlorine compounds,
      lindane, and dieldrin. MATERIALS AND METHODS: A fluorescent dye transfer assay
      was used to quantify gap junction-mediated communication and sensitivity to
      lindane and dieldrin. Analyses of connexin 43, PKC, ERK, GSK-3beta, Raf, and Akt
      kinase phosphorylation were performed by Western blotting. RESULTS: Pre
      incubation of astroglial cells with 10 microM ChK prevented inhibition of dye
      transfer by lindane and dieldrin, which correlates with stabilization of the
      connexin 43 P2 isoform, and addition of ChK after lindane or dieldrin reversed
      the inhibitory effect, which correlated with re-appearance of the P2 isoform.
      Using phosphorylation site-specific antibodies, we demonstrated that lindane,
      dieldrin, and ChK all activated p44/42 ERK, but only ChK activated Akt kinase.
      ChK also activated a downstream effector of Akt, GSK-3beta, and activation of
      both kinases was inhibited by Wortmannin. Wortmannin also blocked ChK's ability
      to prevent dieldrin-induced inhibition of gap junction-mediated communication
      between RG-2 cells. CONCLUSION: ChK's protective effects, both preventative and
      reversal, on lindane and dieldrin inhibition of gap junction-mediated
      communication are associated with stabilization and reappearance of the connexin
      43 P2 phosphoform and may be mediated by the Akt pathway.

PMID- 18040760
TI  - Velocity distribution and shear rate variability resulting from changes in the
      impeller location in the USP dissolution testing apparatus II.
AB  - PURPOSE: The United States Pharmacopoeia (USP) imposes strict requirements on the
      geometry and operating conditions of the USP Dissolution Testing Apparatus II. A
      previously validated Computational Fluid Dynamics (CFD) approach was used here to
      study the hydrodynamics of USP Apparatus II when the impeller was placed at four
      different locations, all within the limits specified by USP. METHOD: CFD was used
      to predict the velocity profiles, energy dissipation rates, and strain rates when
      the impeller was placed in the reference location (centrally mounted, 25 mm off
      the vessel bottom), 2 mm off-center, 2 mm higher, and 2 mm lower than the
      reference location. RESULTS: Small changes in impeller location, especially if
      associated with loss of symmetry, produced extensive changes in velocity profiles
      and shear rates. Centrally located impellers, irrespective of their off-bottom
      clearance, produced non-uniform but nearly symmetric strain rates. The off-center
      impeller produced a more uniform but slightly asymmetric strain rate
      distribution. CONCLUSIONS: The system hydrodynamics depends strongly on small
      differences in equipment configurations and operating conditions, which are
      likely to affect significantly the flow field and shear rate experienced by the
      oral dosage form being tested, and hence the solid-liquid mass transfer and
      dissolution rate.

PMID- 18040762
TI  - The vacuolar (H+)-ATPase: subunit arrangement and in vivo regulation.
AB  - The V-ATPases are responsible for acidification of intracellular compartments and
      proton transport across the plasma membrane. They play an important role in both
      normal processes, such as membrane traffic, protein degradation, urinary
      acidification, and bone resorption, as well as various disease processes, such as
      viral infection, toxin killing, osteoporosis, and tumor metastasis. V-ATPases
      contain a peripheral domain (V1) that carries out ATP hydrolysis and an integral
      domain (V0) responsible for proton transport. V-ATPases operate by a rotary
      mechanism involving both a central rotary stalk and a peripheral stalk that
      serves as a stator. Cysteine-mediated cross-linking has been used to localize
      subunits within the V-ATPase complex and to investigate the helical interactions
      between subunits within the integral V0 domain. An essential property of the V
      ATPases is the ability to regulate their activity in vivo. An important mechanism
      of regulating V-ATPase activity is reversible dissociation of the complex into
      its component V1 and V0 domains. The dependence of reversible dissociation on
      subunit isoforms and cellular environment has been investigated.

PMID- 18040763
TI  - China: policy and practice of MCH since the early 1990s.
AB  - Since the socioeconomic reforms in China in the late 1970s the improvement of
      maternal and child health (MCH), which was once considered one of the great
      achievements of China after 1949, has slowed and some indicators show that the
      situation in some regions, especially in rural areas, is getting worse instead of
      better. This article will focus on policy and policy-related issues in the
      delivery of MCH services. It will cover historical changes in policy and their
      effects, especially in the financing of MCH. In addition, it will also touch upon
      new practices of MCH in the new cooperative medical scheme (NCMS) in present-day
      rural China.

PMID- 18040764
TI  - A comparative study of interleukin-1beta production and p2x7 expression after ATP
      stimulation by peripheral blood mononuclear cells isolated from rheumatoid
      arthritis patients and normal healthy controls.
AB  - Interleukin 1 beta (IL-1beta) is a proinflammatory cytokine that is considered to
      play an important role in the progression of rheumatoid arthritis (RA). A
      stimulus such as ATP is necessary to cause the release of mature IL-1beta, via
      activation of the P2X(7) receptor on monocytes. In this study, the production of
      IL-1beta in whole blood after ATP stimulation and expression of P2X(7) receptors
      in RA and healthy subjects were examined. Blood samples from RA patients or
      healthy controls were stimulated with ATP in the presence of lipopolysaccharide
      (LPS). Supernatants were harvested and IL-1beta levels were measured by enzyme
      linked immunosorbent assay (ELISA). Expression of P2X(7) receptors was measured
      using flow cytometry. ATP induced significantly higher levels of IL-1beta in LPS
      activated RA blood samples compared to controls. A significant up-regulation of
      P2X(7) receptor expression on mononuclear cells was observed after overnight
      incubation with ATP without any significant differences between RA patients and
      normals. These data suggest that RA patient mononuclear cells are more sensitive
      to ATP stimulation than healthy individuals perhaps due to genetic polymorphism
      in the P2X(7) gene.

PMID- 18040761
TI  - Pharmaceutical particle engineering via spray drying.
AB  - This review covers recent developments in the area of particle engineering via
      spray drying. The last decade has seen a shift from empirical formulation efforts
      to an engineering approach based on a better understanding of particle formation
      in the spray drying process. Microparticles with nanoscale substructures can now
      be designed and their functionality has contributed significantly to stability
      and efficacy of the particulate dosage form. The review provides concepts and a
      theoretical framework for particle design calculations. It reviews experimental
      research into parameters that influence particle formation. A classification
      based on dimensionless numbers is presented that can be used to estimate how
      excipient properties in combination with process parameters influence the
      morphology of the engineered particles. A wide range of pharmaceutical
      application examples -- low density particles, composite particles,
      microencapsulation, and glass stabilization -- is discussed, with specific
      emphasis on the underlying particle formation mechanisms and design concepts.

PMID- 18040765
TI  - Impact of transvenous ventricular pacing leads on tricuspid regurgitation in
      pediatric and congenital heart disease patients.
AB  - INTRODUCTION: Transvenous ventricular pacing leads across the tricuspid valve may
      cause or exacerbate tricuspid regurgitation (TR). The literature in adults is
      inconclusive and no studies have investigated the association between pacing
      leads and TR in children or congenital heart disease patients. METHODS AND
      RESULTS: A retrospective chart review was conducted at a large children's
      hospital, yielding 123 patients with initial placement of a transvenous lead
      across their tricuspid valve that had adequate echocardiographic data for review.
      The median age was 16 years (range 2-52) at time of lead placement. The pre
      procedure echo was compared both to the first echo after lead placement and the
      most recent echo. Median time was 242 days from implant to first echo, and 827
      days to most recent echo. There was no difference in TR between the pre-procedure
      echo and first follow-up echo (p = NS). However, TR was more likely to progress
      mildly between the pre-procedure echo and the most recent echo (p < 0.02) with a
      mean increase from 1.54 to 1.69 on a 0 to 4 ordinal scale. There were 76 pts
      (62%) with CHD. Mean pre-procedure TR was 1.82 in right-sided valvular CHD (e.g.,
      tetralogy of Fallot, repaired AV canal) vs. 1.43 without right-sided CHD (p <
      0.01). CONCLUSIONS: In patients with transvenous ventricular leads across the
      tricuspid valve, echocardiography demonstrates a small, but statistically
      significant change in TR. The detected change is minimal, suggesting that there
      is little impact of transvenous leads on TR, even in growing children or patients
      with right-sided structural heart disease.

PMID- 18040766
TI  - Inhibition of HPV-16 L1 expression from L1 cDNAs correlates with the presence of
      hnRNP A1 binding sites in the L1 coding region.
AB  - The human papillomavirus type 16 (HPV-16) L1 capsid protein is very poorly
      expressed from cDNA expression plasmids transiently transfected into mammalian
      cells. The results described herein demonstrate that inhibition of HPV-16 L1
      expression from L1 cDNAs correlates with the presence of splicing regulatory
      sequences in the L1 coding region. This inhibitory effect correlates with the
      binding of hnRNP A1 to the RNA elements. Similar to unutilised splice sites that
      may retain mRNAs in the nucleus, regulatory splicing RNA elements may also
      inhibit gene expression in the absence of splicing. The results presented here
      explain the inefficient expression of HPV-16 L1 protein from the wild type L1
      cDNA expression plasmids in mammalian cells. These results may be of general
      interest since alteration of RNA sequences to prevent unwanted RNA-protein
      interactions may increase expression of many different genes in transient
      transfections or after plasmid uptake in DNA vaccination approaches.

PMID- 18040767
TI  - Study of the genetic stability of measles virus CAM-70 vaccine strain after
      serial passages in chicken embryo fibroblasts primary cultures.
AB  - To evaluate the genetic stability of the CAM-70 measles vaccine strain we have
      performed 10 serial passages of the seed lot virus FMS-7 in chicken embryo
      fibroblasts primary cultures (CEF) under production conditions. The nucleotide
      sequences of the seed lot virus, the virus from a vaccine vial (third passage)
      and from the 10th passage were determined and compared with each other and with
      sequences from other sources. The full genome analysis of the CAM-70 vaccine
      still considers it as the most divergent among all vaccine strains. The
      nucleotide sequence analyses of viral genomes from the three CAM-70 passage
      levels have demonstrated that they are identical. This study shows that the
      measles CAM-70 vaccine virus is highly adapted to its cultivation conditions and
      that its genetic stability contributes, in part, to the safety profile of the
      vaccine.

PMID- 18040768
TI  - Factors that influence sexual arousal in men: a focus group study.
AB  - The goal of this study was to improve our understanding of men's sexual response
      and its components as well as the factors or types of situations that men
      describe as facilitating or interfering with sexual arousal. Six focus groups,
      involving 50 mostly white, heterosexual men (M age = 35.2 years; range, 18-70),
      were conducted. As it was previously found in women (Graham, Sanders, Milhausen,
      & McBride, Archives of Sexual Behavior, 33, 527-538, 2004), men described a wide
      range of physical (genital as well as nongenital) and cognitive/affective cues
      for sexual arousal. Also, men described the relationship between sexual desire
      and arousal as being variable and complex, presented a wide range of factors that
      increased or decreased sexual arousal, and showed substantial variability in both
      the importance and direction of their effects. The findings may help further
      development of models of sexual response and inform discussions about gender
      differences in sexual desire and arousal.

PMID- 18040769
TI  - Childhood gender nonconformity and harassment as predictors of suicidality among
      gay, lesbian, bisexual, and heterosexual Austrians.
AB  - The role of childhood gender role nonconformity (CGNC) and childhood harassment
      (CH) in explaining suicidality (suicide ideation, aborted suicide attempts, and
      suicide attempts) was examined in a sample of 142 lesbian, gay, and bisexual
      (LGB) adults and 148 heterosexual adults in Austria. Current and previous
      suicidality, CGNC, and CH were significantly greater in LGB participants compared
      to heterosexual participants. After controlling for CGNC, the effect of sexual
      orientation on CH diminished. CGNC correlated significantly with current
      suicidality in the LGB but not in the heterosexual group, and only non
      significant correlations were found for CGNC with previous suicidality.
      Controlling for CH and CGNC diminished the effect of sexual orientation on
      current suicidality. Bayesian multivariate analysis indicated that current
      suicidality, but not previous suicidality, depended directly on CGNC. CH and CGNC
      are likely implicated in the elevated levels of current suicidality among adult
      LGB participants. As for previous suicidality, the negative impact of CGNC on
      suicidality might be overshadowed by stress issues affecting sexual minorities
      around coming out. The association of CGNC with current suicidality suggests an
      enduring effect of CGNC on the mental health and suicide risk of LGB individuals.

PMID- 18040770
TI  - Twin analysis on paired comparison data.
AB  - Current behavior genetic models can only employ limited types of phenotypic data,
      such as Likert scale data or continuous data, as variables. Here, a new method
      employing paired comparison data is presented within the framework of behavior
      genetic models. This model facilitates the estimation of genetic, shared
      environmental, and non-shared environmental contributions to paired comparison
      variables. Paired comparison methods are sensitive to differences in preferences
      between items, even when the true preferences are markedly similar. An extended
      model that combines Likert variables, and which enables the estimation of
      genetic, shared environmental, and non-shared environmental correlations, is also
      presented. Simulations are then performed to demonstrate the characteristics of
      these models. Finally, a real data example is introduced. Mplus script is
      included in the appendix.

PMID- 18040771
TI  - Preliminary evidence of effects of crisis intervention team training on self
      efficacy and social distance.
AB  - OBJECTIVE: The Crisis Intervention Team (CIT) program is a collaborative model
      involving mental health professionals and law enforcement officers that is being
      implemented in a multitude of localities across the country. This study had two
      main objectives: (1) To assess perceptions of self-efficacy and desired social
      distance of control officers and officers entering CIT training with regard to
      individuals with psychiatric syndromes (depression and schizophrenia) and
      individuals with substance dependence (alcohol and cocaine), and (2) To examine
      the effects, if any, of CIT training on self-efficacy and social distance.
      METHODS: Between March and July 2006, a survey was administered to 34 control
      police officers, 58 officers just before a 40-h CIT training program, and 40 of
      these officers upon completion of the training. RESULTS: At baseline, pre-CIT
      officers did not differ from control non-CIT officers in terms of self-efficacy
      or social distance relating to the four disorders. Officers trained in CIT
      demonstrated enhanced self-efficacy for interacting with individuals with
      depression, cocaine dependence, schizophrenia, and alcohol dependence.
      Additionally, CIT-trained officers reported reduced social distance regarding
      individuals with these four psychiatric conditions. Regarding the schizophrenia
      vignette, there was a significant interaction between pre-CIT/post-CIT status and
      family history of psychiatric treatment in the prediction of social distance.
      CONCLUSIONS: Enhancements in self-efficacy and reductions in social distance may
      have important implications in terms of improving officers' interactions with
      people with mental illnesses and substance use disorders. Given the importance of
      the problem of law enforcement/criminal justice involvement among people with
      such illnesses, and the dearth of research on this growing collaborative service
      model, further research is needed on officer-level outcomes of the CIT program.

PMID- 18040772
TI  - Advancing the science of implementation: a workshop summary.
AB  - While much has been written about reducing the gap between science and practice,
      relatively little progress has been made to develop a sound knowledge base
      underlying implementation of effective interventions. To respond to these
      challenges, the National Institute of Mental Health organized a workshop
      entitled, "Advancing the Science of Implementation: Improving the Fit between
      Mental Health Intervention Development and Service Systems." Over the 2-day
      workshop, a multi-disciplinary group of intervention and services researchers,
      implementers, methodologists, organizational theorists, and clinicians was
      brought together in an "engaged scholarship" * format composed of small and large
      group settings to discuss the development of a sound knowledge base on the
      implementation of evidence-based practices. Using three specific intervention
      categories, participants identified constructs seen to be important to the
      implementation of the model in real-world systems. Following each breakout
      session, attendees reconvened for a full group discussion and brief presentations
      were conducted to highlight interventions in the areas of organizational
      measures, social network analysis and field opportunities. This summary describes
      some of the constructs relevant to implementation research and presents research
      questions that, if studied, will lay a solid foundation for implementation
      research.

PMID- 18040773
TI  - Rapid genotyping using real-time fluorescent PCR of the Trp64Arg polymorphism of
      the beta3-adrenergic receptor gene and the -3826 A to G variant of the uncoupling
      protein-1 gene.

PMID- 18040774
TI  - Why do electromagnetic pulses enhance bone growth?
AB  - The excitation probability of substrate molecules involved in the production of
      growth factors influencing the division of chondrocytes in the growth layer of
      bone under the influence of pulsed electromagnetic fields is studied
      theoretically in a quantum mechanical model calculation. In this model matrix
      elements and anti-bonding energy levels are assumed known and the dynamics of the
      interaction with pulsed electromagnetic fields is derived. The derivation makes
      it clear that continuous pulsing or large driving currents can overwhelm local
      diffusive transport to the growth plane resulting in a loss of its enhancement
      properties. Optimal locations within a pair of Helmholtz coils for enhancement of
      bone growth are also investigated and found to be close to the coils. The work
      presented here is believed to be the first derivation in a model calculation of a
      physical basis for the effects of pulsed electromagnetic fields on bone growth
      and fusion.

PMID- 18040775
TI  - Mammalian Ste20-like protein kinase 3 mediates trophoblast apoptosis in
      spontaneous delivery.
AB  - The placenta is essential in transferring gases and nutrients from the mother to
      the developing fetus. Trophoblast apoptosis may cause labor or other pregnancy
      related disorders. This study demonstrated the essential role of Mst3, a human
      Ste20-like protein kinase, in the oxidative stress-induced apoptosis of
      trophoblasts of term placenta in normal spontaneous delivery. Oxidative stress,
      but not hormones released during labor such as prostaglandin E1, oxytocin or
      angiotensin II, induces the expression of Mst3 and apoptosis of human term
      placenta after elective Cesarean section without labor pain. The role of Mst3 in
      oxidative stress-induced apoptosis was further demonstrated in the 3A-sub-E, a
      human trophoblast cell line. The H2O2-induced apoptosis of 3A-sub-E cells was
      largely suppressed by overexpressed Mst3KR, the kinase-dead mutant or by
      selective knockdown of endogenous Mst3. Further studies showed that Jun N
      terminal kinase (JNK) may participate in the signaling pathway of H2O2-induced
      apoptosis by mediating the level of Mst3. Subsequently, caspase 3 and other
      downstream apoptotic components may be activated by Mst3 and trigger the
      apoptotic process in human trophoblasts.

PMID- 18040778
TI  - Microglia as a pharmacological target in infectious and inflammatory diseases of
      the brain.
AB  - Following an eclipse of scientific inquiry regarding the biology of microglia
      that lasted 50 years, recognition toward the end of the 20th century of their
      neuropathogenic role in HIV-associated dementia and in
      neuroinflammatory/neurodegenerative diseases fueled a renaissance of interest in
      these resident macrophages of the brain parenchyma. Results of a large number of
      in vitro studies, using isolated microglial cells or glial/neuronal cell
      cultures, and parallel findings emerging from animal models and clinical studies
      have demonstrated that activated microglia produce a myriad of inflammatory
      mediators that both serve important defense functions against invading
      neurotropic pathogens and have been implicated in brain damage in infectious as
      well as neuroinflammatory/neurodegenerative diseases, such as multiple sclerosis,
      Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This
      review provides a brief background regarding the physiological and
      pathophysiological roles of microglia and highlights current pharmacological
      approaches that target activated microglia with the goal of ameliorating
      infectious and neuroinflammatory/neurodegenerative diseases of the brain.
      Although this aspect of the field of neuroimmunopharmacology is in its infancy,
      it holds great promise for developing new treatments and prevention of diseases
      that are, in many cases, epidemic throughout the world.

PMID- 18040779
TI  - Microglia biology in health and disease.
AB  - Microglia cells are resident central nervous system (CNS) leukocytes that
      regulate innate immunity and participate in adaptive immune responses in CNS
      tissue. However, microglia cells also appear to play an important role during
      normal function of the mature nervous system. In response to injury, ischemia,
      and inflammatory stimuli, microglia cells assume an activated phenotype
      associated with proliferation, migration to the site of injury, phagocytosis of
      cellular debris, and elaboration (Power and Proudfoot 2001) of both neurotoxic
      and neurotrophic factors. Recent reports strongly suggest that regulating
      microglia function may be a fruitful future therapeutic target for the prevention
      of neurological dysfunction in a variety of CNS injuries and chronic diseases.
      Thus, developing a thorough understanding of extracellular signals that activate
      microglia as well as a complete catalogue of microglia responses to activating
      stimuli in both the healthy and diseased state are crucial scientific endeavors.
      This review presents the current understanding of the biology of microglia during
      normal CNS function as well as in response to CNS injury or neurodegenerative
      disease. In addition, microglia modulate both the activation and down-regulation
      of the adaptive immune response in the CNS. Evidence that microglia cells play a
      primary role in regulating CNS immune responses will also be discussed.

PMID- 18040780
TI  - Mechanisms of neuroimmunity and neurodegeneration associated with HIV-1 infection
      and AIDS.
AB  - Infection with the human immunodeficiency virus-1 (HIV-1) and acquired
      immunodeficiency syndrome (AIDS) are a persistent health problem worldwide. HIV-1
      seems to enter the brain very soon after peripheral infection and can induce
      severe and debilitating neurological problems that include behavioral
      abnormalities, motor dysfunction, and frank dementia. Infected peripheral immune
      competent cells, in particular macrophages, appear to infiltrate the CNS and
      provoke a neuropathological response involving all cell types in the brain. The
      course of HIV-1 disease is strongly influenced by viral and host factors, such as
      the viral strain and the response of the host's immune system. In addition, HIV-1
      dependent disease processes in the periphery have a substantial effect on the
      pathological changes in the central nervous system (CNS), although the brain
      eventually harbors a distinctive viral population of its own. In the CNS, HIV-1
      also incites activation of chemokine receptors, inflammatory mediators,
      extracellular matrix-degrading enzymes, and glutamate receptor-mediated
      excitotoxicity, all of which can initiate numerous downstream signaling pathways
      and disturb neuronal and glial function. Although there have been many major
      improvements in the control of viral infection in the periphery, an effective
      therapy for HIV-1-associated dementia (HAD) is still not available. This article
      addresses recently uncovered pathologic neuroimmune and degenerative mechanisms
      contributing to neuronal damage induced by HIV-1 and discusses experimental and
      potentially future therapeutic approaches.

PMID- 18040781
TI  - New insights into the neuroimmunity of SIV infection by magnetic resonance
      spectroscopy.
AB  - (1)H magnetic resonance spectroscopy (MRS) was employed to noninvasively monitor
      neuronal injury in eight rhesus macaques infected with simian immunodeficiency
      virus (SIV), whose immune system was compromised by CD8 T lymphocyte depletion
      and treated with highly active antiretroviral therapy (HAART). SIV infection and
      CD8 depletion resulted in a rapid decline in cerebral N-acetylaspartate (NAA)
      levels, a sensitive marker of neuronal health. Within 3 months of SIV infection
      and CD8 depletion, four animals developed AIDS and severe SIV encephalitis. The
      other four macaques underwent daily doses of HAART beginning 4 weeks after
      infection/CD8 depletion. HAART involved drugs that do not penetrate the central
      nervous system (CNS) including 9-[2(R)-(phosphonomethoxy)propyl]adenine and a
      racemic mixture of D: -L: -enantiomers of 2',3'-dideoxy-5-fluoro-3'thiacytidine.
      HAART resulted in reversal of NAA/Cr decline after 4 weeks of therapy, and no
      virus or encephalitis was found in brain samples analyzed. These results indicate
      that the CNS injury in AIDS is entirely dependent on events involving the
      peripheral immune system mediated by trafficking of SIV-infected monocytes into
      the brain. The rapid decline in NAA/Cr with SIV infection/CD8 depletion and its
      rapid recovery with HAART suggest that: (1) infected monocyte turnover in the CNS
      is rapid, occurring in days to weeks; (2) there are endogenous mechanisms that
      reverse neuronal injury; and (3) a threshold level of infected
      monocytes/macrophages in the CNS is required to overcome the neuronal recovery
      processes. These observations explain the clinical success of antiretroviral
      therapy in reducing the incidence of HIV-associated dementia and minor
      cognitive/motor disorder and suggest novel targets for drug development.

PMID- 18040783
TI  - Neurobiology of multiple insults: HIV-1-associated brain disorders in those who
      use illicit drugs.
AB  - Despite two decades of research, certain aspects of HIV-related central nervous
      system (CNS) disease remain poorly understood. HIV targets microglia and
      macrophages within the CNS and enters the brain compartment early. However, HIV
      is there held in check apparently until the onset of significant immune
      compromise, when viral replication, microglial activation, neuronal damage, and
      cognitive impairment are likely to ensue. Illicit drug abuse continues to be a
      significant risk factor for HIV transmission worldwide. Whether HIV-related CNS
      disease is more prevalent or more severe in this risk group has long been
      debated. Drugs of abuse can of themselves cause immune suppression, blood-brain
      barrier breakdown, microglial activation, and neuronal injury. This review
      presents evidence that HIV associated CNS disorders are indeed accentuated in
      drug abusers. However, the advent of effective therapy has added a new dimension,
      which must be taken into consideration. Treated individuals are surviving much
      longer and HIV encephalitis and HIV-associated dementia have become much less
      common. However, more subtle forms of CNS damage are emerging. Examination of the
      brains of individuals who have been treated long term with highly active
      antiretroviral therapy (HAART) reveals a surprising degree of microglial
      activation, comparable at times to that seen formerly in milder cases of HIV
      encephalitis. In addition, these individuals show evidence of increased
      deposition of neurodegenerative proteins, particularly hyperphosphorylated tau.
      Similar observations have been made in young opiate abusers who are HIV negative.
      Taken together, these results suggest that neuroinflammation and
      neurodegeneration, which are clinically silent at present, may cause problems in
      the future in HAART-treated subjects.

PMID- 18040786
TI  - Does inflammation in an autoimmune disease differ from inflammation in
      neurodegenerative diseases? Possible implications for therapy.
AB  - Accumulating evidence suggests that neurodegenerative diseases of the central
      nervous system (CNS) are associated with a local inflammatory response. CNS
      autoimmune diseases are also associated with inflammation. Does this mean that
      all neurodegenerative diseases are autoimmune in nature? Does it imply that
      autoimmune and neurodegenerative diseases are both eligible for the same therapy?
      What distinguishes between the two types of disease? Do they differ both in
      etiology and in pathology, or do they have different etiologies but similar
      pathology and progression? In this minireview we offer a new view of the
      inflammatory differences between neurodegenerative and autoimmune diseases in the
      CNS and discuss the implications for therapy.

PMID- 18040782
TI  - Neuroimmunity and the blood-brain barrier: molecular regulation of leukocyte
      transmigration and viral entry into the nervous system with a focus on neuroAIDS.
AB  - HIV infection of the central nervous system (CNS) can result in neurologic
      dysfunction with devastating consequences in a significant number of individuals
      with AIDS. Two main CNS complications in individuals with HIV are encephalitis
      and dementia, which are characterized by leukocyte infiltration into the CNS,
      microglia activation, aberrant chemokine expression, blood-brain barrier (BBB)
      disruption, and eventual damage and/or loss of neurons. One of the major
      mediators of NeuroAIDS is the transmigration of HIV-infected leukocytes across
      the BBB into the CNS. This review summarizes new key findings that support a
      critical role of the BBB in regulating leukocyte transmigration. In addition, we
      discuss studies on communication among cells of the immune system, BBB, and the
      CNS parenchyma, and suggest how these interactions contribute to the pathogenesis
      of NeuroAIDS. We also describe some of the animal models that have been used to
      study and characterize important mechanisms that have been proposed to be
      involved in HIV-induced CNS dysfunction. Finally, we review the pharmacologic
      interventions that address neuroinflammation, and the effect of substance abuse
      on HIV-1 related neuroimmunity.

PMID- 18040787
TI  - Role of immunity in recovery from a peripheral nerve injury.
AB  - Motoneurons are large multipolar neurons with cell bodies located in the
      brainstem and spinal cord, and peripheral axons ending in neuromuscular
      junctions. Peripheral nerve damage, outside the blood-brain barrier (BBB),
      results in both retrograde changes centrally and anterograde changes along the
      length of the axon distal to the lesion site. Often, peripheral nerve damage is
      accompanied by motoneuron cell death, unless axon regrowth and target
      reconnection occur so that the target muscle can provide essential neurotrophic
      factors. It is essential that the motoneuron cell body survive during the process
      of reconnection so that the source for essential axon-rebuilding proteins is
      assure(of a fact)/ensured (results). A commonly used peripheral injury paradigm
      is that of facial nerve transection at its exit from the skull through the
      stylomastoid foramen so that nerve reconnection to the facial muscle tissue is
      permanently prevented. This model system allows for the study of the mechanisms
      responsible for maintaining facial motoneuron (FMN) cell body survival, without
      the complicating factor of axon regrowth. Injury to the nervous system results in
      an immune response that is either neuroprotective or neurodestructive. Findings
      suggest that FMN survival after facial nerve axotomy depends on the action of a
      CD4(+) T cell that is initially activated peripherally and subsequently
      reactivated centrally. This review will summarize what is known about the neural
      immune players involved in FMN survival and repair, so that the pharmacological
      manipulation of this interaction will one day become evident for the clinical
      management of neurological situations.

PMID- 18040789
TI  - Macrophage colony-stimulating factor in the pathogenesis of HIV infection:
      potential target for therapeutic intervention.
AB  - Macrophage colony stimulating factor (M-CSF) appears to play a major role in
      promoting and maintaining reservoirs of human immunodeficiency virus type 1 (HIV
      1) in infected individuals. HIV-1 infection induces production of M-CSF by
      macrophages, which in turn promotes further infection of macrophages via
      increases in CD4 and CCR5 receptors, as well as increases in virus gene
      expression. M-CSF promotes the ontogeny and survival of macrophages, contributing
      to both the number and longevity of these infected cells. M-CSF dysregulation
      promotes the differentiation of monocytes toward macrophages and osteoclasts and
      at the same time may inhibit differentiation toward dendritic cells, resulting in
      immune impairment. The potential role of M-CSF in HIV-associated end organ
      diseases including HIV-associated dementia, HIV-associated nephropathy, and
      osteoporosis is discussed. This review emphasizes the need for developing M-CSF
      antagonists for treatment of HIV-1-infected patients.

PMID- 18040788
TI  - Protecting the synapse: evidence for a rational strategy to treat HIV-1
      associated neurologic disease.
AB  - Loss of synaptic integrity and function appears to underlie neurologic deficits
      in patients with HIV-1-associated dementia (HAD) and other chronic
      neurodegenerative diseases. Because synaptic injury often long precedes neuronal
      death and surviving neurons possess a remarkable capacity for synaptic repair and
      functional recovery, we hypothesize that therapeutic intervention to protect
      synapses has great potential to improve neurologic function in HAD and other
      diseases. We discuss findings from both HAD and Alzheimer's disease to
      demonstrate that the disruption of synaptic structure and function that can occur
      during excitotoxic injury and neuroinflammation represents a likely substrate for
      neurologic deficits. Based on available evidence, we provide a rationale for
      future studies aimed at identifying molecular targets for synaptic protection in
      neurodegenerative disease. Whereas patients with HAD beginning antiretroviral
      therapy have shown reversal of neurologic symptoms that is unique for patients
      with chronic neurodegenerative conditions, we propose that the potential for such
      reversal is not unique.

PMID- 18040790
TI  - Neuroimmunity, drugs of abuse, and neuroAIDS.
AB  - It has long been postulated that drugs of abuse may represent significant
      cofactors in the progression of human immunodeficiency virus (HIV)-induced
      disease. Both HIV infection and drugs of abuse have significant effect on the
      immune system as well as on the nervous system. In HIV infection, abnormalities
      in these systems intersect to lead to a constellation of symptoms known as
      neuroAIDS. Drugs of abuse may synergize with such damage, acting on immune and/or
      neural cells. However, definitive epidemiological evidence for such an
      interaction is lacking. Here we review such studies as well as the use of the
      nonhuman primate/simian immunodeficiency virus system to investigate the
      interaction of neuroAIDS with drugs of abuse. Furthermore, recent findings on
      mechanisms of actions of selected drugs reveal the possibility of protective as
      well as detrimental effects on the central nervous system damage induced by HIV.

PMID- 18040791
TI  - Cannabinoid-induced immune suppression and modulation of antigen-presenting
      cells.
AB  - The study of marijuana cannabinoid biology has led to many important discoveries
      in neuroscience and immunology. These studies have uncovered a new physiological
      system, the endocannabinoid system, which operates in the regulation of not only
      brain function but also the regulation of the immune system. Studies examining
      the effect of cannabinoid-based drugs on immunity have shown that many cellular
      and cytokine mechanisms are suppressed by these agents leading to the hypothesis
      that these drugs may be of value in the management of chronic inflammatory
      diseases. In this report, we review current information on cannabinoid ligand and
      receptor biology, mechanisms involved in immune suppression by cannabinoids with
      emphasis on antigen-presenting cells, and preclinical and clinical models
      analyzing the therapeutic potential of cannabinoid-based drugs.

PMID- 18040792
TI  - Combined and independent effects of chronic marijuana use and HIV on brain
      metabolites.
AB  - The effects of chronic marijuana (MJ) use on brain function remain controversial.
      Because MJ is often used by human immunodeficiency virus (HIV) patients, the aim
      of this study was to evaluate whether chronic MJ use and HIV infection are
      associated with interactive or additive effects on brain chemistry and cognitive
      function. We evaluated 96 subjects (30 seronegative nondrug users, 24 MJ users,
      21 HIV without MJ use, 21 HIV + MJ) using proton magnetic resonance spectroscopy
      and a battery of neuropsychological tests. The two primarily abstinent MJ user
      groups showed no significant differences on calculated estimates of lifetime
      grams of delta9-tetrahydrocannabinol exposure, despite some differences in usage
      pattern. The two HIV groups also had similar HIV disease severity (CD4 cell
      count, plasma viral load, HIV dementia staging, Karnofsky score). On two-way
      analyses of covariance, HIV infection (independent of MJ) was associated with
      trends for reduced N-acetyl aspartate (NA) in the parietal white matter and
      increased choline compounds (CHO) in the basal ganglia. In contrast, MJ
      (independent of HIV) was associated with decreased basal ganglia NA (-5.5%, p =
      0.05), CHO (-10.6%, p = 0.04), and glutamate (-9.5%, p = 0.05), with increased
      thalamic creatine (+6.1%, p = 0.05). HIV + MJ was associated with normalization
      of the reduced glutamate in frontal white matter (interaction p = 0.01). After
      correction for age, education, or mood differences, MJ users had no significant
      abnormalities on neuropsychological test performance, and HIV subjects only had
      slower reaction times. These findings suggest chronic MJ use may lead to
      decreased neuronal and glial metabolites, but may normalize the decreased
      glutamate in HIV patients.

PMID- 18040793
TI  - Modulation of immune function by morphine: implications for susceptibility to
      infection.

PMID- 18040794
TI  - Leukocyte-derived opioid peptides and inhibition of pain.
AB  - In peripheral inflamed tissue interactions between leukocyte-derived opioid
      peptides and opioid receptors on sensory neurons lead to potent, clinically
      relevant inhibition of pain. Opioid receptors are present on peripheral terminals
      of sensory neurons and are upregulated in inflammation. Their endogenous ligands,
      opioid peptides, are synthesized in circulating immune cells, which migrate to
      injured tissues directed by chemokines and adhesion molecules. Under stressful
      stimuli or in response to releasing agents (e.g., corticotropin-releasing factor,
      cytokines, catecholamines) leukocytes can secrete opioids. These peptides
      activate peripheral opioid receptors and produce analgesia by inhibiting the
      excitability of sensory nerves and/or the release of excitatory neuropeptides.
      These effects occur without central opioid side effects such as depression of
      breathing, clouding of consciousness, or addiction. Future research should
      elucidate the selective targeting of opioid peptide-containing immune cells to
      sites of painful tissue injury and the augmentation of opioid peptide and
      receptor synthesis.

PMID- 18040795
TI  - Impact of opiate-HIV-1 interactions on neurotoxic signaling.
AB  - Opiate drug abuse exacerbates the pathogenesis of human immunodeficiency virus-1
      (HIV-1) in the central nervous system through direct actions on glia and neurons.
      Opiate abuse causes widespread disruption of astroglial and microglial function,
      and significant increases in astroglial-derived proinflammatory cytokines and
      chemokines, which likely contributes to neuronal dysfunction, death, and HIV
      encephalitis. Neurons are also directly affected by opiate-HIV-1 interactions.
      HIV-1 and the viral proteins gp120 and Tat activate multiple caspase-dependent
      and caspase-independent proapoptotic pathways in neurons involving
      phosphatidylinositol 3-kinase (PI3 kinase)/Akt, as well as p38, c-Jun N-terminal
      kinase (JNK) and/or other mitogen-activated protein kinases (MAPKs). Opiates
      appear to decrease the threshold for HIV-1-mediated neurotoxicity by sending
      convergent signals that exacerbate proapoptotic events induced by viral and
      cellular toxic products. The synergistic proinflammatory and neurotoxic effects
      of opiate drugs on glia and neurons are largely mediated through mu opioid
      receptors, which are expressed by subpopulations of astroglia, microglia, and
      neurons. Opiate abuse intrinsically modifies the host response to HIV-1.
      Identification of how this occurs is providing considerable insight toward
      understanding the mechanisms underlying HIV-1-associated dementia.

PMID- 18040796
TI  - Enhanced immune sensitivity to stress following chronic morphine exposure.
AB  - Chronic administration of escalating doses ofmorphine leads to neuroadaptive
      changes precipitating development of tolerance to many of the acute effects of
      morphine, such as analgesia, activation of the hypothalamic-pituitary-adrenal
      (HPA) axis and suppression of immune cell activities. Interestingly, morphine
      tolerance has also been shown to be accompanied by heightened immunosuppressive
      effects of restraint stress using a rodent model. These observations have led to
      the hypothesis that the altered neuronal state accompanying opioid tolerance may
      contribute to this enhanced immune sensitivity to stress. To further test this
      hypothesis using different stressors, Sprague-Dawley rats were treated
      chronically with morphine for at least 8 days and then challenged with either
      psychological (water stress) or systemic stressors [morphine withdrawal,
      lipopolysaccharide (10 mug/kg i.p. challenge)]. It was found that, independent of
      the type of stress employed, morphine-tolerant animals displayed significantly
      lower mitogen-stimulated blood lymphocyte responses when compared to the
      responses of similarly treated saline controls. To determine whether direct
      activation of central stress pathways may also lead to enhanced immune
      sensitivity, morphine-tolerant animals were centrally injected with IL-1beta (1
      ng/mul i.c.v.), a cytokine that activates the HPA axis by central mechanisms.
      Similar to the other types of stress, this direct central challenge was also
      found to be more immunosuppressive in morphine-tolerant animals compared to
      controls. Collectively, these studies demonstrate that morphine-tolerant animals
      have an enhanced susceptibility to the debilitating effects of a variety of
      stressors on immune cell function, an effect that is likely due to the
      neuroadaptive changes that develop during chronic morphine exposure.

PMID- 18040798
TI  - Debate: "is increasing neuroinflammation beneficial for neural repair?".

PMID- 18040799
TI  - Up-regulation of BDNF in astrocytes by TNF-alpha: a case for the neuroprotective
      role of cytokine.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is widely known to be involved in
      physiological and pathophysiological processes of the brain where this
      proinflammatory cytokine is implicated with regulation of inflammatory and
      survival components. We report that TNF-alpha up-regulates exon-IV-bdnf mRNA and
      brain-derived neurotrophic factor (BDNF) protein in primary astrocytes. The BDNF
      protein was detectable both in cellular lysate and in the extracellular medium.
      Activation of NF-kappaB by TNF-alpha and inhibition of TNF-alpha-induced BDNF
      expression by Deltap65 (a dominant-negative mutant) and NEMO-binding domain
      peptide (an inhibitor of NF-kappaB) suggests that TNF-alpha induces BDNF
      expression through the activation of NF-kappaB. Similarly, TNF-alpha induced the
      activation of C/EBPbeta and the expression of BDNF was sensitive to
      overexpression of DeltaC/EBPbeta (a dominant-negative mutant) and ETO (an
      inhibitor of C/EBPbeta). Among three MAP kinases, TNF-alpha-induced BDNF up
      regulation was sensitive only to inhibitors of ERK MAP kinase. However, the ERK
      MAP kinase pathway was coupled to activation of C/EBPbeta but not NF-kappaB.
      Taken together, this study identifies a novel property of TNF-alpha in inducing
      the expression of BDNF via NF-kappaB and C/EBPbeta in astrocytes that may be
      responsible for neurotrophic activity of the cytokine.

PMID- 18040801
TI  - Effects of opioid tolerance and withdrawal on the immune system.
AB  - Review of the robust literature using acute drug injection paradigms points
      clearly to the conclusion that morphine is immunosuppressive. In contrast,
      studies of the effect of subacute or chronic administration of morphine on immune
      function is limited, with variable results. In some cases tolerance to the
      immunosuppressive effects of the drug is clearly demonstrated, but in other
      cases, selected immune parameters do not demonstrate tolerance. Discrepancies in
      findings may result from differences in species or route and manner of drug
      administration. Even fewer studies (total of 10) have been published on the
      effects of withdrawal on immune function. Most immune parameters tested are
      suppressed following drug withdrawal. Recovery time to baseline response levels
      varies in the studies. In the single report of withdrawal in humans, immune
      function was suppressed for up to 3 years. It is clearly established that
      withdrawal suppresses capacity of murine spleen cells to make an ex vivo antibody
      response, which contrasts with evidence of polarization of the lymphocytes
      towards a Th2 phenotype. Several laboratories have shown that subacute and
      chronic exposure to morphine, as well as drug withdrawal, sensitize to the lethal
      effects of bacterial lipopolysaccharide. Underlying sepsis, combined with
      morphine-induced hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis,
      may be occult variables modulating immune responses during opioid administration
      and withdrawal. As episodes of withdrawal are common among drug abusers, more
      intensive investigation is warranted on the effects of withdrawal on immune
      function, on mechanisms of immune modulation, and on sensitization to infection.

PMID- 18040800
TI  - Blood-brain barrier: structural components and function under physiologic and
      pathologic conditions.
AB  - The blood-brain barrier (BBB) is the specialized system of brain microvascular
      endothelial cells (BMVEC) that shields the brain from toxic substances in the
      blood, supplies brain tissues with nutrients, and filters harmful compounds from
      the brain back to the bloodstream. The close interaction between BMVEC and other
      components of the neurovascular unit (astrocytes, pericytes, neurons, and
      basement membrane) ensures proper function of the central nervous system (CNS).
      Transport across the BBB is strictly limited through both physical (tight
      junctions) and metabolic barriers (enzymes, diverse transport systems). A
      functional polarity exists between the luminal and abluminal membrane surfaces of
      the BMVEC. As a result of restricted permeability, the BBB is a limiting factor
      for the delivery of therapeutic agents into the CNS. BBB breakdown or alterations
      in transport systems play an important role in the pathogenesis of many CNS
      diseases (HIV-1 encephalitis, Alzheimer's disease, ischemia, tumors, multiple
      sclerosis, and Parkinson's disease). Proinflammatory substances and specific
      disease-associated proteins often mediate such BBB dysfunction. Despite seemingly
      diverse underlying causes of BBB dysfunction, common intracellular pathways
      emerge for the regulation of the BBB structural and functional integrity. Better
      understanding of tight junction regulation and factors affecting transport
      systems will allow the development of therapeutics to improve the BBB function in
      health and disease.

PMID- 18040802
TI  - Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent
      macaques.
AB  - The immune effects of chronic opiate exposure and/or opiate withdrawal are not
      well understood. The results of human studies with opiate abusers are variable
      and may not be able to control for important factors such as subjects' drug
      histories, health and nutritional status. Nonhuman primate models are necessary
      to control these important factors. A model of opiate dependence in macaques was
      developed to study the effects of opiate dependence and withdrawal on measures of
      immune function. Four pigtailed macaques drank a mixture of morphine (20
      mg/kg/session) and orange-flavored drink every 6 h for several months. During
      stable morphine dependence, absolute numbers of neutrophils, monocytes and
      lymphocytes did not change relative to pre-morphine levels. However, there was a
      significant decrease in the absolute number and percentage of natural killer (NK)
      cells in morphine dependence. Either precipitated withdrawal or abstinence for 24
      h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte
      counts decreased and absolute netrophil counts increased significantly in
      withdrawal, relative to levels during morphine dependence. Lymphocyte subset
      (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little
      change in their percentage distributions. There was, however, a significant
      increase in the percentage of NK cells in withdrawal relative to levels during
      morphine dependence. This study demonstrates the usefulness of voluntary oral
      self-dosing procedures for maintaining morphine dependence in nonhuman primates
      and demonstrates that the morphine withdrawal syndrome includes large alterations
      in blood parameters of immune system function, including nearly 50% reduction in
      numbers of CD4+, CD8+ and CD20+ cells.

PMID- 18040803
TI  - Opioid receptors and signaling on cells from the immune system.
AB  - This review discusses the criteria for determining whether a binding site or
      functional response is directly mediated by either the mu, delta, or kappa opioid
      receptors. In 1988, Sibinga and Goldstein published the first review that
      addressed whether cells from the immune system express opioid receptors. The
      criteria that they used, namely, structure-activity relationships,
      stereoselectivity, dose- and concentration-dependence, and saturability are still
      relevant criteria today for determining if an immunological response is mediated
      by either the mu, delta or kappa opioid receptors. Radioligand receptor binding
      studies and functional studies that clearly show the presence of an opioid
      receptor on immunocytes are presented. Selective agonists and antagonists for the
      mu, delta, and kappa opioid receptors are discussed, and the need for their use
      in experiments is emphasized. Conditions used in functional assays are very
      important. Receptor desensitization and downregulation occur within minutes after
      the application of an agonist. However, many immunological assays are applying an
      agonist for days before measuring an immunological effect. The results obtained
      may reflect changes that are results of receptor desensitization and/or
      downregulation instead of changes that are observed with acute activation of the
      receptor. The future of receptor pharmacology lies in the crosstalk and
      dimerization of G protein-coupled receptors. In transfected systems, opioid
      receptors have been shown to dimerize with chemokine and cannabinoid receptors,
      resulting in crosstalk between different types of receptors.

PMID- 18040804
TI  - Nuclear factor kappaB signaling in opioid functions and receptor gene expression.
AB  - Opiates are the most powerful of all known analgesics. The prototype opiate
      morphine has been used as a painkiller for several thousand years. Chronic usage
      of opiates not only causes drug tolerance, dependence, and addiction, but also
      suppresses immune functions and affects cell proliferation and cell survival. The
      diverse functions of opiates underscore the complexity of opioid receptor
      signaling. Several downstream signaling effector systems, including adenylyl
      cyclase, mitogen-activated protein kinase, Ca2+ channels, K+ channels, and
      phosphatidylinositol 3-kinase/Akt, have been identified to be critical in opioid
      functions. Nuclear factor-kappaB (NF-kappaB), one of the most diverse and
      critical transcription factors, is one of the downstream molecules that may
      either directly or indirectly transmit the receptor-mediated upstream signals to
      the nucleus, resulting in the regulation of the NF-kappaB-dependent genes, which
      are critical for the opioid-induced biological responses of neuronal and immune
      cells. In this minireview, we focus on current understanding of the involvement
      of NF-kappaB signaling in opioid functions and receptor gene expression in cells.

PMID- 18040806
TI  - Methamphetamine modulates DC-SIGN expression by mature dendritic cells.
AB  - We report that methamphetamine (meth) may act as cofactor in human
      immunodeficiency virus (HIV)-1 pathogenesis by increasing dendritic cell (DC)
      specific intercellular adhesion molecule-3 (ICAM-3) grabbing non-integrin (DC
      SIGN) expression on DCs. Mature DCs (MDCs), obtained from normal subjects,
      cultured with meth show an up-regulation of DC-SIGN gene and protein expression
      as analyzed by real-time quantitative polymerase chain reaction and fluorescence
      activated cell-sorting analyses, respectively. Furthermore, these meth-induced
      effects were reversed by a dopamine D1 receptor antagonist (SCH 23390) and small
      interfering RNA specific to the D1 receptor (D1R) demonstrating that meth-induced
      effects are mediated through these receptors. Furthermore, meth in synergy with
      the HIV-1 peptide gp120 up-regulates DC-SIGN gene expression by MDCs. These data
      are the first evidence that meth up-regulates the expression of DC-SIGN on MDCs.
      A better understanding of the role of DC-SIGN in HIV-1 infection may help to
      design novel therapeutic strategies against the progression of HIV-1 disease in
      the drug-using population.

PMID- 18040805
TI  - Drugs of abuse, immune modulation, and AIDS.
AB  - Illicit drugs such as amphetamines, cocaine, marijuana, and opiates alter immune
      function and decrease host resistance to microbes in vitro and in experimental
      animal models. Effects on the immune system may be mediated indirectly as a
      result of drug interactions in the central nervous system (CNS) or directly
      through activation of cognate receptors on various immune cell types. For
      marijuana and opioids, seven-transmembranal G protein-coupled receptors have been
      identified in the CNS and in the immune system that may play a functionally
      relevant role in immune modulation. There is accumulating evidence that sigma(1)
      receptors play a comparable role in cocaine-mediated alteration of immune
      responses. A mode by which these exogenously introduced substances affects
      immunity and host resistance may be by perturbing the balance of Th(1)
      proinflammatory versus Th(2) anti-inflammatory cytokines and lipid bioeffectors.
      However, while illicit drugs have been documented to alter immune functions in
      vitro and in animal models, there is a paucity of controlled longitudinal
      epidemiological studies that definitively correlate immunosuppressive effects
      with increased incidence of infections or immune disorders in humans, including
      infection with the human immunodeficiency virus (HIV) or disease progression to
      AIDS.

PMID- 18040808
TI  - Effects of inhalant nitrites on VEGF expression: a feasible link to Kaposi's
      sarcoma?
AB  - Because inhalant nitrites (commonly known as "poppers") were thought to be
      rapidly cleared from the body, the lay literature has somewhat downplayed their
      toxicity. However, scientific reports have documented their immunosuppressive
      effects in animals, and epidemiological studies have implicated their use with
      the development of Kaposi's sarcoma (KS) in humans. Because inhalant nitrites are
      exogenous nitric oxide donors, we hypothesized that these substances of abuse
      might exert part of their toxicological effects through this biochemical product,
      which has been shown to alter gene regulation and angiogenesis. In a series of
      studies, we showed that acute and chronic in vivo exposure to isobutyl nitrite (a
      representative inhalant nitrite) produced significant tissue-dependent
      alterations in the expression of a number of cancer- and angiogenesis-related
      genes in mice. In particular, hepatic mRNA and protein expression of vascular
      endothelial growth factor (VEGF) was significantly stimulated. The in vivo growth
      rate of a subcutaneous VEGF-responsive tumor was also shown to be accelerated by
      inhalant nitrite exposure. Because the development of KS is extensively linked to
      VEGF and its receptors, the purported link between inhalant nitrites and KS may
      be explained mechanistically, at least in part, through the stimulation of VEGF
      expression by these inhalants.

PMID- 18040807
TI  - Endocannabinoids and reactive nitrogen and oxygen species in neuropathologies.
AB  - Neuropathologies that affect our population include ischemic stroke and
      neurodegenerative diseases of immune origin, including multiple sclerosis. The
      endocannabinoid system in the brain, including agonists anandamide (arachidonyl
      ethanolamide) and 2-arachidonoylglycerol, and the CB1 and CB2 cannabinoid
      receptors, has been implicated in the pathophysiology of these disease states,
      and can be a target for therapeutic interventions. This review concentrates on
      cellular signal transduction pathways believed to be involved in the cellular
      damage.

PMID- 18040809
TI  - MDR- and CYP3A4-mediated drug-drug interactions.
AB  - P-glycoprotein (P-gp), multiple drug resistance associated proteins (MRPs), and
      cytochrome P450 3A4 together constitute a highly efficient barrier for many
      orally absorbed drugs. Multidrug regimens and corresponding drug-drug
      interactions are known to cause many adverse drug reactions and treatment
      failures. Available literature, clinical reports, and in vitro studies from our
      laboratory indicate that many drugs are substrates for both P-gp and CYP3A4. Our
      primary hypothesis is that transport and metabolism of protease inhibitors (PIs)
      and NNRTIs will be altered when administered in combination with azole
      antifungals, macrolide, fluroquinolone antibiotics, statins, cardiovascular
      agents, immune modulators, and recreational drugs [benzodiazepines, cocaine,
      lysergic acid dithylamide (LSD), marijuana, amphetamine (Meth), 3,4
      methylenedioxymethamphetamine (MDMA), and opiates] due to efflux, and/or
      metabolism at cellular targets. Therefore, such drug combinations could be a
      reason for the unexpected and unexplainable therapeutic outcomes. A number of
      clinical reports on drug interaction between PIs and other classes (macrolide
      antibiotics, azole antifungals, cholesterol lowering statins, cardiovascular
      medicines, and immunomodulators) are discussed in this article. MDCKII-MDR1 was
      employed as an in vitro model to evaluate the effects of antiretrovirals, azole
      antifungals, macrolide, and fluroquinolone antibiotics on efflux transporters.
      Ketoconazole (50 muM) enhanced the intracellular concentration of (3)H ritonavir.
      The inhibitory effects of ketoconazole and MK 571 on the efflux of (3)H ritonavir
      were comparable. An additive effect was observed with simultaneous incorporation
      of ketoconazole and MK 571. Results of (3)H ritonavir uptake studies were
      confirmed with transcellular transport studies. Several fluroquinolones were also
      evaluated on P-gp-mediated efflux of (3)H cyclosporin and 14C erythromycin. These
      in vitro studies indicate that grepafloxacin, levofloxacin, and sparfloxacin are
      potent inhibitors of P-gp-mediated efflux of 14C erythromycin and (3)H
      cyclosporin. Simultaneous administration of fluoroquinolones and macrolides could
      minimize the efflux and metabolism of both of the drugs. Effects of erythromycin
      and ketoconazole on carbamazepine metabolism were examined. Formation of 10,11
      epoxy carbamazepine, a major CBZ metabolite, was significantly inhibited by these
      agents. Therefore, drug efflux proteins (P-gp, MRPs) and metabolizing enzyme
      (CYP450) are major factors in drug interactions. Overlapping substrate
      specificities of these proteins result in complex and sometimes perplexing
      pharmacokinetic profiles of multidrug regimens. Drug-drug interactions with PIs
      and other coadministered agents for human immunodeficiency virus (HIV) positive
      population have been discussed in light of efflux transporters and metabolizing
      enzymes. This article provides an insight into low and variable oral
      bioavailability and related complications leading to loss of therapeutic activity
      of MDR and CYP 450 substrates.

PMID- 18040810
TI  - Nanotechnology: a focus on nanoparticles as a drug delivery system.
AB  - This review will provide an in-depth discussion on the previous development of
      nanoparticle-based drug delivery systems (DDS) and discuss original research data
      that includes the therapeutic enhancement of antiretroviral therapy. The use of
      nanoparticle DDS will allow practitioners to use drugs to target specific areas
      of the body. In the treatment of malignancies, the use of nanoparticles as a DDS
      is making measurable treatment impact. Medical imaging will also utilize DDS to
      illuminate tumors, the brain, or other cellular functions in the body. The
      utility of nanoparticle DDS to improve human health is potentially enormous.

PMID- 18040811
TI  - NeuroAIDS, drug abuse, and inflammation: building collaborative research
      activities.
AB  - Neurological complications of human immunodeficiency virus (HIV) infection are a
      public health problem despite the availability of active antiretroviral
      therapies. The neuropathogenesis of HIV infection revolves around a complex
      cascade of events that include viral infection and glial immune activation,
      monocyte-macrophage brain infiltration, and secretion of a host of viral and
      cellular inflammatory and neurotoxic molecules. Although there is evidence that
      HIV-infected drug abusers experience more severe neurological disease, the
      biological basis for this finding is unknown. A scientific workshop organized by
      the National Institute on Drug Abuse (NIDA) was held on March 23-24, 2006 to
      address this question. The goal of the meeting was to bring together basic
      science and clinical researchers who are experts in NeuroAIDS, glial immunity,
      drugs of abuse, and/or pharmacology in order to find new approaches to
      understanding interactions between drug abuse and neuroAIDS. The format of the
      meeting was designed to stimulate open discussion and forge new multidisciplinary
      research collaborations. This report includes transcripts of active discussions
      and short presentations from invited participants. The presentations were
      separated into sections that included: Glial Biology, Inflammation, and HIV;
      Pharmacology, Neurotoxicology, and Neuroprotection; NeuroAIDS and Virology; and
      Virus-Drug and Immune-Drug Interactions. Research priorities were identified.
      Additional information about this meeting is available through links from the
      NIDA AIDS Research Program website (
      http://www.nida.nih.gov/about/organization/arp/arp-websites.htm ).

PMID- 18040812
TI  - A novel mechanism for immunosuppression: from neuropeptides to regulatory T
      cells.
AB  - Vasoactive intestinal peptide (VIP), a well-known immunoregulatory neuropeptide,
      affects both innate and adaptive immunity, and acts as a major anti-inflammatory
      factor in animal models of autoimmune diseases. VIP down-regulates the innate
      immune response by inhibiting the release of proinflammatory cytokines,
      chemokines, and nitric oxide by activated macrophages, microglia, and dendritic
      cells. VIP affects the adaptive immune response by reducing the costimulatory
      capacity of antigen-presenting cells, and by preferentially inducing Th(2)-type
      responses. This is accomplished through preferential Th(2) differentiation,
      enhanced survival of Th(2) effectors, and the induction of Th(2)-attracting
      chemokines. Recently, we discovered a novel mechanism for the immunosuppressive
      effect of VIP that involves the generation of antigen-specific regulatory T cells
      (Treg) through the induction of tolerogenic dendritic cells (tDC). In this work,
      we review the VIP-induced Treg generation both in vivo and in vitro, and the use
      of VIP-generated Treg in two models of autoimmunity, i.e., collagen-induced
      arthritis and experimental autoimmune encephalomyelitis, and in bone marrow
      transplantation as related to graft-versus-host disease and the graft-versus
      leukemia response.

PMID- 18040813
TI  - Abnormal striatal dopaminergic synapses in National NeuroAIDS Tissue Consortium
      subjects with HIV encephalitis.
AB  - People with human immunodeficiency virus (HIV)/acquired immune deficiency
      syndrome (AIDS) have neurological problems that overlap with diseases associated
      with abnormal dopaminergic (DAergic) synaptic transmission, including subcortical
      dementia, motor slowing, psychosis, and drug addiction. Previous study has
      suggested that DAergic tone may be decreased in HIV/AIDS, but biochemical
      confirmation of that tenet is still lacking. To that end, this study addresses
      the neurochemical interaction between HIV infection and DAergic synaptic
      transmission in human brain specimens. Protein markers of DAergic synapses were
      characterized in homogenates of the corpus striatum from individuals with HIV
      encephalitis (HIVE) and seronegative controls from the autopsy cohort of the
      National NeuroAIDS Tissue Consortium. Striatal DAergic markers were abnormal in
      HIVE. Abnormal presynaptic markers included decreased tyrosine hydroxylase (TH)
      protein and decreased phosphorylated TH. The presynaptic dopamine reuptake
      transporter (DAT) was increased reciprocally. Postsynaptic abnormalities included
      decreased dopamine receptor type 2 (D(2)R) and increased D(3)R. There was
      preferential loss of the alternatively spliced long isoform of D(2)R relative to
      the short isoform. Abnormal DAergic synapse proteins were significantly
      correlated with the HIV Gag mRNA transcripts amplified in striatal extracts.
      These synaptic changes resemble shifts that occur when DAergic tone is increased
      experimentally. Increased DAergic tone leads to heightened salience for drugs of
      abuse, increases behaviors that increase the risk of HIV transmission, and might
      decrease compliance with antiretroviral medication regimens.

PMID- 18040814
TI  - Stress-induced immune dysregulation: implications for wound healing, infectious
      disease and cancer.
AB  - The communication between the central nervous system and the immune system occurs
      via a complex network of bidirectional signals linking the nervous, endocrine and
      immune systems. The field of psychoneuroimmunology (PNI) has provided new
      insights to help understand the pathophysiological processes that are linked to
      the immune system. Work in this field has established that psychological stress
      disrupts the functional interaction between the nervous and immune systems.
      Stress-induced immune dysregulation has been shown to be significant enough to
      result in health consequences, including reducing the immune response to
      vaccines, slowing wound healing, reactivating latent herpesviruses, such as
      Epstein-Barr virus (EBV), and enhancing the risk for more severe infectious
      disease. Chronic stress/depression can increase the peripheral production of
      proinflammatory cytokines, such as interleukin (IL)-6. High serum levels of IL-6
      have been linked to risks for several conditions, such as cardiovascular disease,
      type 2 diabetes, mental health complications, and some cancers. This overview
      will discuss the evidence that psychological stress promotes immune dysfunction
      that negatively impacts human health.

PMID- 18040815
TI  - A role for corticosterone in impaired intestinal immunity and barrier function in
      a rodent model of acute alcohol intoxication and burn injury.
AB  - Alcohol (EtOH) intoxication and burn injury independently activate hypothalamic
      pituitary-adrenal (HPA) axis, and glucocorticoids, the end product of the HPA
      axis, play a role in shaping the immune response under those conditions. By
      utilizing a rat model of acute EtOH intoxication and burn injury, studies in our
      laboratory have investigated the role of corticosterone (i.e., glucocorticoids in
      rodents) in altered intestinal immunity and barrier function following a combined
      insult of EtOH and burn injury. Results from these studies suggest that EtOH
      intoxication prior to burn injury augments corticosterone release, which in turn
      suppresses intestinal T cell function by inhibiting mitogen-activated protein
      kinase (i.e., p38 and ERK) pathway. Furthermore, we found that corticosterone
      does not directly alter the intestinal barrier function; rather, it up-regulates
      interleukin-18, which then directly or indirectly contributes to impaired
      intestinal barrier function. The loss of intestinal immunity/barrier function may
      result in increased bacterial translocation and thereby contribute to postinjury
      pathogenesis, leading to sepsis and organ dysfunction in burn patients as well as
      in patients with a history of EtOH intoxication.

PMID- 18040816
TI  - Role of corticosterone in immunosuppressive effects of acute ethanol exposure on
      Toll-like receptor mediated cytokine production.
AB  - Acute ethanol (EtOH) exposure causes a stress response in humans, nonhuman
      primates, and rodents. Previous study results indicate that the suppression of
      some immunological parameters by EtOH is mediated in part or completely by
      elevated corticosterone concentrations induced by EtOH. However, initial results
      suggested that corticosterone is not involved in the modulation of cytokine
      production by macrophages in response to polyinosinic polycytidylic acid (poly
      I:C). New studies were conducted to further evaluate the role of corticosterone
      in EtOH-mediated changes in production of interleukin-6 (IL-6), IL-10, and IL-12
      in serum and peritoneal fluid in mice treated with poly I:C or lipopolysaccharide
      (LPS). Suppression of IL-6, but not IL-12, production by EtOH was found to be
      mediated by corticosterone. However, poly I:C, LPS, and EtOH all caused similar
      elevations of corticosterone concentrations; thus, it is not clear if EtOH is
      required to induce levels or durations of corticosterone needed to mediate the
      observed effects. The situation with IL-10 was more complicated. Inhibition of
      corticosterone synthesis with aminoglutethimide prevented the increase in IL-10
      production caused by EtOH plus poly I:C as compared to poly I:C only. This
      indicates that this increase is dependent on corticosterone, but exogenous
      corticosterone plus poly I:C did not increase IL-10 production. Thus, EtOH and
      corticosterone are required. However, with LPS inhibition of corticosterone
      synthesis (using aminoglutethimide) or inhibition of its action (using
      mifepristone) further increased, or did not affect IL-10 concentrations,
      suggesting fundamental differences in the signaling pathways leading from poly
      I:C and LPS to IL-10 production.

PMID- 18040818
TI  - HIV Preclinical-Clinical Therapeutics Research: central nervous system
      approaches.
AB  - The prevalence of HIV-associated brain disorders is reportedly increasing due, in
      part, to the prolonged life span of individuals who are surviving well on highly
      active antiretroviral treatments (HAART). While clinicians report CNS-related
      deficits that are more subtle in presentation than the frank dementia evident in
      the pre-HAART era, the milder presentation continues to substantively reduce an
      individual's quality of life. The development of novel drugs or therapeutic
      strategies for treating HIV-related CNS disease is important as most
      investigators agree that the brain is a sanctuary for latent virus, local viral
      recrudescence, and associated brain inflammatory responses. The prolonged chronic
      and cumulative effects on the brain of living with HIV-related inflammatory
      processes, antiretroviral treatments, and their long-term side effects,
      toxicities, and brain-related aging processes collectively indicate that the
      burden of CNS and PNS complications will increase profoundly during the upcoming
      years. Considering the high expense for new drugs entering CNS-related clinical
      trials and their ultimately low success rate, the NIMH convened a meeting
      entitled, HIV Preclinical-Clinical Therapeutics Research Meeting, to discuss the
      current and proposed novel approaches for neuroAIDS drug development and clinical
      practices. The purposes of the meeting were twofold: to identify the most
      promising approaches for future neuroAIDS therapeutics development research and
      to discuss optimal structures and partnerships with industry that may facilitate
      the successful movement of compounds from the bench to the bedside. Several
      themes can be derived from the sessions and are highlighted below for
      preclinical, translational and clinical neuroAIDS therapeutics research.

PMID- 18040817
TI  - Postoperative pain management and proinflammatory cytokines: animal and human
      studies.
AB  - The postoperative period is associated with neuroendocrine, metabolic, and immune
      alterations, which are the combined result of tissue damage, anesthesia,
      postoperative pain, and psychological stress. Limited evidence indicates that
      pain management in the postoperative period can affect the outcome of the
      surgery, reducing cardiac, pulmonary, and metabolic complications. Recent
      evidence indicates that pain and immune factors, especially proinflammatory
      cytokines, mutually interact and influence each other. A series of animal studies
      demonstrates that effective preemptive analgesia improved postoperative recovery,
      and this effect was enhanced by coadministration of IL-1ra together with the
      preemptive analgesics. Furthermore, preemptive analgesia attenuated surgery
      induced PGE(2) production in the amygdala and the activation of the HPA axis. IL
      1 signaling is required for the production of amygdala PGE(2) in response to
      surgical stress, and may thus affect the physiological and psychological aspects
      of surgical stress. These reports suggest that short-term effective analgesia can
      have long-lasting beneficial effects on surgery recovery. They further suggest
      that IL-1 blockade should be considered in the clinical management of pain
      associated with peripheral or nerve injury. Another series of human studies
      describes an interaction between the effectiveness of postoperative pain relief
      and surgery-associated immune alterations: In three separate studies, the more
      effective pain management technique was associated with diminished surgery
      induced immune alterations, especially diminished elevation of IL-1. Reduced
      elevation of postoperative IL-1 and effective pain relief may both contribute to
      an attenuated illness response and a better surgery outcome.

PMID- 18040819
TI  - NIMH Preclinical/Clinical Therapeutics Research meeting--preclinical drug
      discovery session.

PMID- 18040820
TI  - Biomarkers, laboratory, and animal models for the design and development of
      adjunctive therapies for HIV-1 dementia and other neuroinflammatory disorders.
AB  - The goals of this component were to discuss the potential for NeuroAIDS
      therapeutics. The presentations included discussions of biomarkers, pathogenic
      mechanisms of disease, laboratory models, and the development of adjunctive
      therapies for neuroinflammatory and neurodegenerative disorders with a focus on
      NeuroAIDS. Talks by Dana Giulian on the use of CSF biomarkers for therapeutic
      trial design in dementia, Howard Fox on the SIV model of NeuroAIDS, Christine
      Zink on minocycline and its antiretroviral activities, and Katrina L. Mealey on
      the means to improve drug access to the brain by regulation P-glycoprotein,
      rounded out the session. It was acknowledged that although a number of compounds
      including selegiline, nimodipine, and memantine were studied in clinical trials
      and showed some trends towards clinical improvement none showed significance.
      Drugs such as minocycline, sodium valproate, and P-glycoprotein regulators were
      discussed and now are being developed. Partnerships between public institutions
      and private companies were discussed. Multidisciplinary teams are likely required
      to see such research to fruition, and the developmental schemes from the molecule
      to the laboratory to the animal to the clinic were discussed and developed in the
      session.

PMID- 18040821
TI  - Translational research models and novel adjunctive therapies for neuroAIDS.
AB  - The goal of this component of the meeting was to discuss novel therapeutics that
      attenuate inflammatory pathways, enhance drug delivery into the brain and/or
      bypass the blood-brain barrier (BBB). Presentations included discussions of (i)
      antiretroviral drugs packaged into nanoparticles by Howard Gendelman, (ii) how to
      engage the nasal epithelium and its closely associated neural fibers as a route
      for drug entry to the brain, by William H. Frey and Lynn Pulliam, and (iii)
      antioxidant gene delivery to neurons using vector systems that can protect
      neurons against HIV-associated toxicity, by David Strayer. The session was capped
      by active discourse among leaders in the field of adjunctive therapies in a broad
      range of scientific disciplines.

PMID- 18040822
TI  - Clinical trials in HIV CNS disease and treatment management.
AB  - On May 15 and 16, 2006, the National Institute of Mental Health sponsored a
      workshop designed to facilitate discussion and collaboration between basic and
      clinical investigators in neuroAIDS. Day 2 of the meeting featured a series of
      talks by clinical investigators. Three of these (those by J. McArthur, P. Tebas,
      and C. Flexner) are described in detail here. The remaining four talks (those by
      R. Ellis, R. Price, S. Letendre, and R. Robertson) are briefly introduced here,
      and full-length papers may be found elsewhere in this issue of the Journal.

PMID- 18040823
TI  - Studying host-pathogen interactions in 3-D: organotypic models for infectious
      disease and drug development.
AB  - Representative, reproducible, and high-throughput models of human cells and
      tissues are critical for a meaningful evaluation of host-pathogen interactions
      and are an essential component of the research developmental pipeline. The most
      informative infection models-animals, organ explants, and human trials-are not
      suited for extensive evaluation of pathogenesis mechanisms and screening of
      candidate drugs. At the other extreme, more cost-effective and accessible
      infection models such as conventional cell culture and static coculture may not
      capture physiological and three-dimensional (3-D) aspects of tissue biology that
      are important in assessing pathogenesis, effectiveness, and cytotoxicity of
      therapeutics. Our lab has used innovative bioengineering technology to establish
      biologically meaningful 3-D models of human tissues that recapitulate many
      aspects of the differentiated structure and function of the parental tissue in
      vivo, and we have applied these models to study infectious disease. We have
      established a variety of different 3-D models that are currently being used in
      infection studies-including small intestine, colon, lung, placenta, bladder,
      periodontal ligament, and neuronal models. Published work from our lab has shown
      that our 3-D models respond to infection with bacterial and viral pathogens in
      ways that reflect the infection process in vivo. By virtue of their physiological
      relevance, 3-D cell cultures may also hold significant potential as models to
      provide insight into the neuropathogenesis of HIV infection. Furthermore, the
      experimental flexibility, reproducibility, cost efficiency, and high-throughput
      platform afforded by these 3-D models may have important implications for the
      design and development of drugs with which to effectively treat neurological
      complications of HIV infection.

PMID- 18040824
TI  - Variation of macrophage tropism among HIV-1 R5 envelopes in brain and other
      tissues.
AB  - Human immunodeficiency virus (HIV)-positive individuals frequently suffer from
      progressive encephelopathy, which is characterized by sensory neuropathy, sensory
      myelopathy, and dementia. Our group and others have reported the presence of
      highly macrophage-tropic R5 variants of HIV-1 in brain tissue of patients with
      neurological complications. These variants are able to exploit low amounts of CD4
      and/or CCR5 for infection and potentially confer an expanded tropism for any cell
      types that express low CD4 and/or CCR5. In contrast to the brain-derived
      envelopes, we found that envelopes from lymph node tissue, blood, or semen were
      predominantly non-macrophage-tropic and required high amounts of CD4 for
      infection. Nevertheless, where tested, the non-macrophage-tropic envelopes
      conferred efficient replication in primary CD4(+) T-cell cultures. Determinants
      of R5 macrophage tropism appear to involve changes in the CD4 binding site,
      although further unknown determinants are also involved. The variation of R5
      envelopes also affects their sensitivity to inhibition by ligands and entry
      inhibitors that target CD4 and CCR5. In summary, HIV-1 R5 viruses vary
      extensively in macrophage tropism. In the brain, highly macrophage-tropic
      variants may represent neurotropic or neurovirulent viruses. In addition,
      variation in R5 macrophage tropism may also have implications (1) for
      transmission, depending on what role macrophages or cells that express low CD4
      and/or CCR5 play in the establishment of infection in a new host, and (2) for
      pathogenesis and depletion of CD4(+) T cells (i.e., do highly macrophage-tropic
      variants confer a broader tropism among CD4(+) T-cell populations late in disease
      and contribute to their depletion?).

PMID- 18040825
TI  - Neurokinin-1 receptor antagonist (aprepitant) inhibits drug-resistant HIV-1
      infection of macrophages in vitro.
AB  - BACKGROUND: Despite the success of antiretroviral therapy in controlling HIV
      replication, treatment failure may ultimately occur in more than 50% of the
      individuals on antiretroviral therapy. Cellular targets offer an attractive
      alternative, as it may be more difficult for HIV to develop resistance to
      alternative cellular inhibitory pathways. We have previously shown that CP
      96,345, a neurokinin-1 receptor (NK-1R) antagonist, inhibits HIV-1 infection of
      macrophages in vitro by downregulating CCR5 expression (Lai JP, Ho WZ, Zhan GX,
      Yi Y, Collman RG, Douglas SD 2001). We have now investigated the effects of a
      Food and Drug Administration (FDA)-approved NK-1R antagonist, aprepitant (Emend),
      on HIV infection of macrophages in an in vitro system. Aprepitant is in clinical
      use for the prevention of nausea and vomiting associated with cancer chemotherapy
      or following surgical procedures. METHODS: Monocytes isolated from healthy donors
      were cultured for 7 days and then treated with or without aprepitant (10(-6) M)
      for 2 h, followed by HIV infection with drug-resistant strains for 2 h. Untreated
      and HIV-infected macrophages were used as controls. Culture supernatants were
      harvested for p24 enzyme-linked immunosorbent assay (ELISA) or HIV reverse
      transcriptase (RT) activity at different time points after infection. R5X4 tropic
      and AZT-resistant strains (R5X4 tropic: A012 and A018) and RT inhibitor-resistant
      HIV strains (R5 tropic: TC60 and TC49) were used for infection. RESULTS:
      Aprepitant suppressed HIV Bal infection of macrophages. Treatment with aprepitant
      (10(-6) M) inhibited infection of macrophages with the AZT-resistant viruses
      (A018, A012) by 0.7 log(10). Aprepitant also suppressed infection of macrophages
      with RT inhibitor-resistant virus (TC 49 and TC 60) by 0.5 log(10). Furthermore,
      aprepitant significantly enhanced the anti-HIV activity of antiretrovirals (AZT,
      Efavirenz, and Indinavir) in HIV Bal-infected macrophages, and aprepitant
      inhibited CCR5 expression on macrophages, ranging from 50.5 to 29.6%. Donor
      heterogeneity was observed in antiviral activity and CCR5 receptor expression.
      CONCLUSION: Aprepitant is active against HIV drug-resistant isolates and enhances
      the anti-HIV activity of the antiretrovirals. Aprepitant downregulates CCR5
      expression on macrophages. NK-1R antagonists merit further investigation as
      potential HIV therapeutic and immunomodulatory agents.

PMID- 18040826
TI  - Neuroprotective and antiretroviral effects of the immunophilin ligand GPI 1046.
AB  - HIV infection results in a neurodegenerative disorder for which currently there
      is no effective therapy available. Currently, available antiretroviral therapy
      has no impact on the production of early regulatory HIV proteins once the virus
      is integrated. Of these proteins, Tat was shown to be toxic to neurons. We, thus,
      used an in vitro neuronal culture system to determine if immunophilin ligands
      could protect against Tat-induced neurotoxicity. We found that GPI 1046 had
      potent neuroprotective effects in this model. The compound was able to protect
      the neurons even though it only partially obliterated Tat-induced oxidative
      stress in neurons, suggesting that other mechanisms may be important in mediating
      its neuroprotective effect. Furthermore, GPI 1046 showed inhibition of HIV
      replication and Tat-mediated long terminal repeat (LTR) activation suggesting
      that this class of compounds may be worthy of further exploration as a potential
      treatment for HIV dementia.

PMID- 18040827
TI  - Facilitating compound progression of antiretroviral agents via modeling and
      simulation.
AB  - Pharmacotherapy in human immunodeficiency virus (HIV)-infected patients and the
      development of safe and effective antiretroviral dosing regimens has been
      hindered by numerous issues, including the rapid development of viral resistance
      to drug therapy, the narrow therapeutic window of the drug compounds, and lack of
      fundamental knowledge concerning the sources of variation in exposure and
      response to antiretroviral agents. Sources of variation may include factors such
      as interpatient differences in genetic expression, immunological response,
      pathogenesis, epidemiologic and socioeconomic factors, and demographics. Modeling
      and simulation (M&S) techniques have become valuable tools to identify and
      quantify variability in exposure and response to antiretroviral agents throughout
      the drug development process. Before actual entry into human safety and
      pharmacokinetic (PK) trials, in vitro screening and in vivo pharmacology studies
      conducted to assess compound potency and compatibility with agents included in
      acceptable antiretroviral therapy (ART) regimens can be characterized via
      quantitative relationships. In addition, physiochemical data is initially used to
      screen drug candidates based on favorable PK and biopharmaceutic properties.
      Compound progression can likewise be supported with M&S exercises to ensure the
      traceability of key assumptions and decisions. The underlying techniques utilize
      nonlinear mixed effect modeling, Monte Carlo simulation, Neural networks, several
      regression-based approaches, and less computationally intensive techniques. The
      application of such an approach promises to be an essential component in the
      development of new agents to treat HIV-1 and is being implemented in the context
      of evaluating Nk1r antagonists as potential candidates to treat NeuroAIDS.

PMID- 18040828
TI  - Biomarkers for neuroAIDS: the widening scope of metabolomics.
AB  - "Metabolomics", the measurement of metabolite concentrations and fluxes in cell
      systems, is an emerging science that has enormous potential and several unique
      characteristics. The current applications for this field are, primarily,
      toxicological profiling and biomarker studies. This review of metabolomics
      research highlights the identification of reliable biomarkers with emphasis on
      neuroAIDS. Such identification of candidate markers will be advantageous for
      tracking the progression of human immunodeficiency virus/central nervous system
      (HIV/CNS) disease to gain maximal benefit from antiretroviral treatment and to
      provide insight into the mechanism of related neuropathogenesis.

PMID- 18040829
TI  - Strategies for intranasal delivery of therapeutics for the prevention and
      treatment of neuroAIDS.
AB  - Intranasal drug administration is a noninvasive method of bypassing the blood
      brain barrier (BBB) to deliver neurotrophins and other therapeutic agents to the
      brain and spinal cord. This method allows drugs that do not cross the BBB to be
      delivered to the central nervous system (CNS) and eliminates the need for
      systemic delivery, thereby reducing unwanted systemic side effects. Delivery from
      the nose to the CNS occurs within minutes along both the olfactory and trigeminal
      neural pathways. Intranasal delivery occurs by an extracellular route and does
      not require that drugs bind to any receptor or undergo axonal transport.
      Intranasal delivery also targets the nasal associated lymphatic tissues (NALT)
      and deep cervical lymph nodes. In addition, intranasally administered
      therapeutics are observed at high levels in the blood vessel walls and
      perivascular spaces of the cerebrovasculature. Using this intranasal method in
      animal models, researchers have successfully reduced stroke damage, reversed
      Alzheimer's neurodegeneration, reduced anxiety, improved memory, stimulated
      cerebral neurogenesis, and treated brain tumors. In humans, intranasal insulin
      has been shown to improve memory in normal adults and patients with Alzheimer's
      disease. Intranasal delivery strategies that can be employed to treat and prevent
      NeuroAIDS include: (1) target antiretrovirals to reach HIV that harbors in the
      CNS; (2) target therapeutics to protect neurons in the CNS; (3) modulate the
      neuroimmune function of moncyte/macrophages by targeting the lymphatics,
      perivascular spaces of the cerebrovasculature, and the CNS; and (4) improve
      memory and cognitive function by targeting therapeutics to the CNS.

PMID- 18040830
TI  - Intranasal tat alters gene expression in the mouse brain.
AB  - Intranasal (IN) delivery of HIV-1 Tat in aging mice was investigated as a
      possible model for HIV-1 infection in the brain. After IN administration, the
      distribution of [(125)I]-labeled Tat in the brains of Swiss Webster mice was
      evaluated by autoradiography and gamma counting. [(125)I]-labeled Tat was
      detected at the highest concentrations in the olfactory bulb, cervical nodes, and
      trigeminal nerve tract. In another experiment, APPSw transgenic mice were used to
      model chronic Tat exposure. The mice were treated intranasally with 6 mug Tat (n
      = 4) or vehicle (n = 4) three times per week for 4 weeks. Total RNA was isolated
      from the frontal cortex, and differential gene expression analysis was performed
      using gene microarrays. Gene ontology profiles indicated innate immunity,
      inflammatory and apoptotic responses. Five genes of interest in the Tat-treated
      mice that were significantly elevated in the microarrays were validated by RT
      PCR. One gene, the Toll-like receptor 9 (Tlr9), has previously been shown to
      activate signaling cascades leading to innate immunity and enhanced HIV-1 gene
      expression. A second gene, Fas, plays a key role in neuroinflammation. Two
      cysteine-rich cytokines associated with chemotaxis were elevated: MCP-1 (Ccl2),
      which is chemotactic for monocytes, and Ccl17 (TARC), which is chemotactic for
      lymphocytes. Finally, the gene sestrin was significantly elevated and has been
      associated with oxidative stress, in particular amyloid beta-induced oxidative
      stress. This IN Tat model of neuroinflammation may be useful to study HIV-1
      induced neurodegeneration.

PMID- 18040831
TI  - Glycogen synthase kinase 3 beta (GSK-3 beta) as a therapeutic target in
      neuroAIDS.
AB  - Highly active antiretroviral therapy (HAART) has made a significant impact on the
      lives of people living with HIV-1 infection. The incidence of neurologic disease
      associated with HIV-1 infection of the CNS plummeted between 1996-2000, but
      unfortunately the number of people currently HIV-1 infected (i.e., prevalence)
      with associated cognitive impairment has been steadily rising. While the reasons
      for this may be multifactorial, the implication is clear: there is a pressing
      need for adjunctive therapy directed at reversing or preventing damage to
      vulnerable pathways in the central nervous system (CNS) from HIV-1 infection.
      Using a team of preclinical and clinical investigators, we have focused our
      efforts on defining how proinflammatory mediators and secretory neurotoxins from
      HIV-1 disrupt signaling of the survival-regulating enzyme, glycogen synthase
      kinase 3 beta (GSK-3beta). In a series of studies initiated using in vitro, then
      in vivo models of HIV-1-associated dementia (HAD), we have demonstrated the
      ability of the mood stabilizing and anticonvulsant drug, sodium valproate (VPA),
      that inhibits GSK-3beta activity and other downstream mediators, to reverse HIV-1
      induced damage to synaptic pathways in the CNS. Based on these results, we
      successfully performed pharmacokinetic and safety and tolerability trials with
      VPA in a cohort of HIV-1-infected patients with neurologic disease. VPA was well
      tolerated in this population and secondary measures of brain metabolism, as
      evidenced by an increase in N-acetyl aspartate/creatine (NAA/Cr), further
      suggested that VPA may improve gray matter integrity in brain regions damaged by
      HIV-1. These findings highlight the therapeutic potential of GSK-3beta blockade.

PMID- 18040832
TI  - Meeting practical challenges of a trial involving a multitude of treatment
      regimens: an example of a multi-center randomized controlled clinical trial in
      neuroAIDS.
AB  - Many clinical trials compare one specific treatment to a control or standard
      treatment. In HIV therapeutics, such fixed-regimen designs may be problematic as
      individualized treatment regimens are standard practice. Designing and
      implementing a trial that allows individualized treatment options poses
      particular challenges. In this example of a clinical trial in NeuroAIDS, it is
      hypothesized that some antiretroviral drugs [i.e., those that penetrate the blood
      brain barrier sufficiently to inhibit HIV in the central nervous system (CNS)]
      will improve HIV neurocognitive impairment, whereas non-penetrating
      antiretrovirals will not be as effective in improving neurocognitive function. To
      test this hypothesis, a uniquely designed strategy trial was developed that
      consists of three essential components: (1) a scoring system that ranks regimens
      for CNS penetration based on semiquantitative criteria, (2) committee-established
      individualized regimen options that allow randomization to opposite ends of the
      CNS penetration spectrum, and (3) timely implementation across multiple centers
      via web-based resources. For the proposed trial, the three components are
      combined with an adaptive randomization scheme to minimize potential confounding
      by several important factors. A small pilot study demonstrated the feasibility
      and acceptability to providers. In conclusion, an innovative design can provide
      solutions to challenging practical issues in trials with multiple treatment
      options.

PMID- 18040833
TI  - Assessment of neuroAIDS in the international setting.
AB  - The global burden of the HIV epidemic is staggering, but in the short term, it is
      largely unfelt in the developed world. Almost one million people have been
      infected with HIV in North America, and the results of effective antiretroviral
      therapy have dramatically improved survival and quality of life. However, there
      are 25 million infected in sub-Saharan Africa alone, and antiretroviral treatment
      is scarce. Ninety-five percent of new infections occur in the developing world
      where resources are limited. Very little is known about NeuroAIDS in the
      developing world where few studies have been conducted on the neurologic and
      neurocognitive effects of antiretroviral treatment. HIV Clade differences and
      other factors could have dramatic effects on treatment effectiveness. There are a
      number of barriers in the assessment of neurological and neurocognitive effects
      in resource limited settings and some of these will be addressed.

PMID- 18040834
TI  - Defining and evaluating HIV-related neurodegenerative disease and its treatment
      targets: a combinatorial approach to use of cerebrospinal fluid molecular
      biomarkers.
AB  - There are a number of reasons that the accomplishments of clinical trials related
      to HIV-related neurodegenerative disease (HRND) and the AIDS dementia complex
      (ADC) have had such limited impact on clinical practice. These include: rapid
      evolution and progress in the treatment of systemic HIV infection that has
      quickly outpaced neurological efforts and has markedly reduced disease incidence;
      ethical constraints that (rightly) demand neurologically compromised patients
      receive the best available treatment before experimental therapeutics;
      complicated backgrounds and comorbidities of patients now most susceptible to
      HRND; and reluctance of general AIDS clinicians and drug companies to look beyond
      systemic or pivotal outcomes. However, the field has also been slow to adopt
      methods that better exploit advances in understanding of the pathogenesis of
      central nervous system (CNS) infection and brain injury, and that might
      circumvent some of these constraints. Using a simple model of pathogenesis, we
      propose an approach to characterizing patients, selecting treatment targets, and
      evaluating outcomes that emphasize a combination of cerebrospinal fluid (CSF)
      markers. This model begins by using three markers related to cardinal components
      of HRND: CNS HIV infection (measurement of CSF HIV RNA), intrathecal
      immunoactivation (CSF neopterin), and brain injury [CSF light chain neurofilament
      (NFL)]. Careful analysis of this and other marker combinations promises more
      rational trial design and more rapid progress in managing CNS HIV infection and
      HRND using both antiviral and adjuvant treatment approaches.

PMID- 18040835
TI  - The role of cohort studies in drug development: clinical evidence of antiviral
      activity of serotonin reuptake inhibitors and HMG-CoA reductase inhibitors in the
      central nervous system.
AB  - BACKGROUND: Effective antiretroviral therapy (ART) has reduced the incidence of
      HIV-associated neurocognitive impairment (HNCI) but its prevalence remains high.
      Clinical trials have yet to identify a consistently effective treatment for HNCI,
      other than ART, but in vitro data support that some drugs approved by the Food
      and Drug Administration (FDA) for other indications might benefit individuals
      with HNCI. Some of these drugs, such as serotonin reuptake inhibitors (SRIs) and
      HMG-CoA reductase inhibitors (statins), may do so by reducing HIV replication in
      the CNS and are already widely used by HIV-infected individuals. METHODS: Six
      hundred fifty-eight HIV-infected participants of the CHARTER cohort had a
      baseline assessment, which included comprehensive neuropsychological (NP) testing
      and HIV RNA measurements in plasma and cerebrospinal fluid (CSF). Four-hundred
      sixty-seven (71%) subjects used ART, 195 (30%) used SRIs, and 63 (10%) used
      statins. RESULTS: SRI users were less likely to have HIV RNA levels in CSF above
      50 copies (c)/mL (29 vs. 37% in non-SRI users, OR 0.69, p = 0.05). This
      association was most evident for three of the seven SRIs (citalopram, sertraline,
      and trazodone, or "antiviral" SRIs, combined 25 vs. 38% in non-SRI users, OR
      0.56, p = 0.01) and was strongest in those not taking concomitant ART (61 vs.
      83%, OR 0.31, p = 0.01). "Antiviral" SRI users also performed better on NP tests
      (median global deficit score 0.37 vs. 0.47, p = 0.04). Statin users were also
      less likely to have HIV RNA levels in CSF above 50 c/mL (16 vs. 37%, p < 0.001)
      but, in contrast to SRIs, the association was strongest in those taking ART (2
      vs. 18%, p < 0.001). Statin use was not associated with better NP performance.
      Multivariate analyses indicated that the use of "antiviral" SRIs-but not statins
      was associated with undetectable HIV RNA levels in CSF and better NP performance.
      CONCLUSIONS: SRIs may reduce HIV replication in CSF and improve NP performance.
      This was particularly true for three SRIs-supporting differences in antiviral
      efficacy between drugs-in individuals who were not taking ART. In contrast,
      statins were not associated with lower HIV replication in CSF in multivariate
      analyses and were not associated with better NP performance. These analyses
      support the value of large observational cohort studies in identifying FDA
      approved drugs that may be worth further investigation.

PMID- 18040836
TI  - The Journal of Neuroimmune Pharmacology reaches its stride.

PMID- 18040837
TI  - The immunology of Alzheimer's disease: prospects towards harnessing disease
      mechanisms for therapeutic ends.

PMID- 18040838
TI  - Recent developments in cell-based immune therapy for neuroblastoma.
AB  - Neuroblastoma (NB) is a common and aggressive tumor of early childhood. To date,
      treatment with chemotherapy, surgery, and radiation therapy has resulted in
      suboptimal outcomes in those with advanced disease. Immune-based treatments hold
      promise for patients with recurrent or advanced NB. Here, recent preclinical
      studies and early stage (phase I) clinical trials using cellular therapeutic
      approaches for NB are reviewed, including studies of natural killer cells,
      gammadelta T cells, chimeric receptor expressing T cells, dendritic cells, and
      allogeneic hematopoietic cell transplant.

PMID- 18040839
TI  - Divergent roles for tumor necrosis factor-alpha in the brain.
AB  - Proinflammatory cytokines and chemokines have been implicated in the pathogenesis
      of several neurological and neurodegenerative disorders. Prominent among such
      factors is the pleiotropic cytokine, tumor necrosis factor (TNF)-alpha. Under
      normal physiological conditions, TNF-alpha orchestrates a diverse array of
      functions involved in immune surveillance and defense, cellular homeostasis, and
      protection against certain neurological insults. However, paradoxical effects of
      this cytokine have been observed. TNF-alpha is elicited in the brain following
      injury (ischemia, trauma), infection (HIV, meningitis), neurodegeneration
      (Alzheimer's, Parkinson's), and chemically induced neurotoxicity. The
      multifarious identity for this cytokine appears to be influenced by several
      mechanisms. Among the most prominent are the regulation of TNFalpha-induced NF
      kappaB activation by adapter proteins such as TRADD and TRAF, and second, the
      heterogeneity of microglia and their distribution pattern across brain regions.
      Here, we review the differential role of TNF-alpha in response to brain injury,
      with emphasis on neurodegeneration, and discuss the possible mechanisms for such
      diverse and region-specific effects.

PMID- 18040840
TI  - Feline immunodeficiency virus neuropathogenesis: from cats to calcium.
AB  - Invasion of human immunodeficiency virus (HIV) into the central and peripheral
      nervous system produces a wide range of neurological symptoms, which continue to
      persist even with adequate therapeutic suppression of the systemic viremia. The
      development of therapies designed to prevent the neurological complications of
      HIV require a detailed understanding of the mechanisms of virus penetration into
      the nervous system, infection, and subsequent neuropathogenesis. These processes,
      however, are difficult to study in humans. The identification of animal
      lentiviruses similar to HIV has provided useful models of HIV infection that have
      greatly facilitated these efforts. This review summarizes contributions made from
      in vitro and in vivo studies on the infectious and pathological interactions of
      feline immunodeficiency virus (FIV) with the nervous system. In vivo studies on
      FIV have provided insights into the natural progression of CNS disease as well as
      the contribution of various risk factors. In vitro studies have contributed to
      our understanding of immune cell trafficking, CNS infection and
      neuropathogenesis. Together, these studies have made unique contributions to our
      understanding of (1) lentiviral interactions at the blood-cerebrospinal fluid
      (CSF) barrier within the choroid plexus, (2) early FIV invasion and pathogenesis
      in the brain, and (3) lentiviral effects on intracellular calcium deregulation
      and neuronal dysfunction. The ability to combine in vitro and in vivo studies on
      FIV offers enormous potential to explore neuropathogenic mechanisms and generate
      information necessary for the development of effective therapeutic interventions.

PMID- 18040841
TI  - Battle of animal models.
AB  - This is a brief summary of the animal models session held during the 12th Annual
      Meeting of the Society on NeuroImmune Pharmacology, Santa Fe, NM, USA. This
      session provided important information for participants on availability and
      utility of animal models for the studies of HIV-1 central nervous system
      infection and drug abuse. It highlighted animal model relevance to human
      disease/condition, its utility for the studies of pathogenesis, potential
      importance for the development of therapeutics, and demonstrated
      limitations/pitfalls.

PMID- 18040842
TI  - WIN55,212-2-mediated inhibition of HIV-1 expression in microglial cells:
      involvement of cannabinoid receptors.
AB  - Cannabinoid receptors CB(1) and CB(2) are primarily expressed in cells of the
      nervous and immune systems, respectively. Recently, the synthetic CB(1)/CB(2)
      agonist WIN55,212-2 was found to suppress replication of HIV-1 in microglial cell
      cultures. The present study was undertaken to test the hypothesis that WIN55,212
      2's antiviral effect is mediated via CB(2) receptors. By reverse transcription
      polymerase chain reaction, microglia were found to express both CB(1) and CB(2)
      receptors. Using additional CB(1)/CB(2) receptor agonists and selective
      antagonists, we found that CB(2) receptors are involved in WIN55,212-2's
      antiviral activity and surprisingly that the CB(1) receptor-selective antagonist
      SR141716A behaved as an agonist in these brain macrophages.

PMID- 18040843
TI  - Oxidative stress kills human primary oligodendrocytes via neutral
      sphingomyelinase: implications for multiple sclerosis.
AB  - Multiple sclerosis (MS) is the most common human demyelinating disease of the
      central nervous system where oxidative stress has been proposed to play an
      important role in oligodendroglial death. However, molecular mechanisms that
      couple oxidative stress to the loss of oligodendrocytes are poorly understood.
      This study underlines the importance of neutral sphingomyelinase-ceramide pathway
      in mediating oxidative stress-induced apoptosis and cell death of human primary
      oligodendrocytes. Various oxidative stress-inducing agents, such as, superoxide
      radical produced by hypoxanthine and xanthine oxidase, hydrogen peroxide,
      aminotriazole capable of inhibiting catalase and increasing intracellular level
      of H2O2, or reduced glutathione-depleting diamide induced the activation of
      neutral sphingomyelinase and the production of ceramide. It is interesting to
      note that antisense knockdown of neutral but not acidic sphingomyelinase ablated
      oxidative stress-induced apoptosis and cell death in human primary
      oligodendrocytes. This study identifies neutral but not acidic sphingomyelinase
      as a target for possible therapeutic intervention in MS.

PMID- 18040844
TI  - The phospholipid mediator platelet-activating factor mediates striatal synaptic
      facilitation.
AB  - The phospholipid mediator platelet-activating factor (PAF), an endogenous
      modulator of glutamatergic neurotransmission, can also be secreted by brain
      mononuclear phagocytes during HIV-1 infection. Platelet-activating factor can
      induce neuronal apoptosis by NMDA receptor-dependent and independent mechanisms.
      We now demonstrate that acute administration of sublethal doses of PAF to
      striatal slices augments synaptic facilitation in striatal neurons following high
      frequency stimulation, which can be blocked by PAF receptor antagonists,
      suggesting that striatal synaptic facilitation can be augmented by PAF receptor
      agonism. We also demonstrate that repeated sublethal doses of PAF during tetanic
      stimulation can greatly increase the magnitude of postsynaptic potentials and
      action potentials, but a lethal dose of PAF destroys the capacity of
      corticostriatal synapses to achieve this augmented synaptic facilitation. Thus,
      the relative concentration and temporal pattern of PAF expression at
      glutamatergic synapses may govern whether it acts in a physiologic or
      pathophysiologic manner during striatal neurotransmission.

PMID- 18040845
TI  - Immunotherapy of human neuroblastoma using umbilical cord blood-derived effector
      cells.
AB  - Tumors of the nervous system, including neuroblastoma and glioblastoma, are
      difficult to treat with current therapies. Despite the advances in cancer
      therapeutics, the outcomes in these patients remain poor and, therefore, new
      modalities are required. Recent literature demonstrates that cytotoxic effector
      cells can effectively kill tumors of the nervous system. In addition, we have
      previously shown that umbilical cord blood (UCB) contains precursors of antitumor
      cytotoxic effector cells. Therefore, to evaluate the antitumor potential of UCB
      derived effector cells, studies were designed to compare the in vitro and in vivo
      antitumor effects of UCB- and peripheral blood (PB)-derived antigen-nonspecific
      and antigen-specific effector cells against tumors of the nervous system.
      Mononuclear cells (MNCs) from UCB were used to generate both interleukin-2 (IL-2)
      activated killer (LAK) cells and tumor-specific cytotoxic T lymphocytes (CTLs).
      UCB-derived LAK cells showed a significant in vitro cytotoxicity against IMR-32,
      SK-NMC, and U-87 human neuroblastoma and glioblastoma, respectively. In addition,
      the CTLs generated using dendritic cells primed with IMR-32 tumor cell lysate
      showed a selective cytotoxicity in vitro against IMR-32 cells, but not against U
      87 or MDA-231 cells. Furthermore, treatment of SCID mice bearing IMR-32
      neuroblastoma with tumor-specific CTLs resulted in a significant (p < 0.01)
      inhibition of tumor growth and increased overall survival. Thus, these results
      demonstrate the potential of UCB-derived effector cells against human
      neuroblastoma and warrant further preclinical studies.

PMID- 18040846
TI  - Kinetic analysis of aggregated amyloid-beta peptide clearance in adult bone
      marrow-derived macrophages from APP and CCL2 transgenic mice.
AB  - Accumulating evidence suggests that bone-marrow (BM)-derived mononuclear
      phagocytes have an important role in the clearance of soluble and aggregated
      amyloid-beta peptides (Abeta) in Alzheimer's disease (AD) brains. However, the
      exact kinetics of Abeta clearance in mononuclear phagocytes derived from
      transgenic animal models of AD expressing beta-amyloid precursor protein (APP)
      mutants have been poorly characterized. We have examined whether CCL2 and APP
      expression affects the clearance of Abeta in conjunction with our control,
      acetylated low-density lipoprotein (AcLDL), using primary cultured BM-derived
      macrophages derived from adult APP, CCL2, APP/CCL2, and control littermates.
      Pulse-chase analysis demonstrated three distinct destinations for Abeta40 and
      AcLDL: intracellular retention, degradation, and secretion. As predicted, 50% of
      Abeta remained intracellularly contained even 5 days after pulse, while 40% of
      degraded and 14% of nondegraded Abeta were secreted. APP/CCL2 macrophages show
      reduced intracellular Abeta retention, along with enhanced secretion of both
      degraded and nondegraded Abeta. Abeta accumulation in aggresome is also partially
      reduced in APP/CCL2 macrophages as compared to other APP, CCL2, or control
      groups, suggesting impaired sorting of aggregated Abeta in aggresomes. The
      degradation of intracranially injected (125)I-Abeta40 aggregates was also
      enhanced in adult APP/CCL2 mice as compared to APP littermates in vivo. These
      data suggest that APP and CCL2 synergistically enhance BM-derived macrophage
      mediated clearance of Abeta. In contrast, the clearance of AcLDL by BM-derived
      macrophages was not significantly enhanced by the presence of either APP or CCL2.

PMID- 18040847
TI  - Microglial activation is required for Abeta clearance after intracranial
      injection of lipopolysaccharide in APP transgenic mice.
AB  - Inflammation has been argued to play a fundamental role in the pathogenesis of
      Alzheimer's disease. Mice transgenic for mutant human amyloid precursor protein
      (APP) develop progressive amyloid deposition, gliosis, and cognitive impairment.
      Paradoxically, intracranial administration of lipopolysaccharide (LPS) to promote
      neuroinflammation results in a reduction in amyloid-beta peptide (Abeta) burden
      concurrent with the inflammatory response. To determine whether microglia mediate
      Abeta clearance after LPS, we used dexamethasone to inhibit the microglial
      response. Amyloid precursor protein mice were injected intrahippocampally with
      either LPS or saline and were allowed to survive for 7 days with or without
      dexamethasone cotreatment. Brain tissue was then analyzed by
      immunohistochemistry. Hippocampal Abeta burden was reduced 7 days after LPS
      injection, and this was prevented by cotreatment with dexamethasone. Markers of
      microglial activation [CD45, complement receptor 3 (CR3), and macrosialin (CD68)]
      were increased by LPS, and these increases were attenuated by dexamethasone.
      Dexamethasone failed to block LPS-induced increases in all microglial markers,
      and Fcgamma receptors II/III and scavenger receptor A were increased by LPS but
      were unaffected by dexamethasone cotreatment. These results indicate a complex
      response by microglia to acute LPS treatment, with only some responses sensitive
      to steroidal anti-inflammatory drug treatment. Nonetheless, microglial activation
      was necessary to remove Abeta in this model of neuroinflammation.

PMID- 18040849
TI  - The protective effect of ischemic postconditioning against ischemic injury: from
      the heart to the brain.
AB  - Postconditioning, a series of mechanical interruptions of reperfusion after
      ischemia, prevents ischemia/reperfusion injury in myocardial infarction. The
      extensive studies of postconditioning in myocardial infarction have led to
      clinical trials. This article reviews the protective effects of postconditioning
      against ischemia from the heart to the brain and provides insights on how studies
      of postconditioning in the field of heart ischemia have shed light on
      postconditioning of the brain. Because brain ischemia has many mechanisms in
      common with heart ischemia, it is logical to test whether postconditioning
      protects against brain ischemia as well. A few groups have reported that
      postconditioning reduces infarct size in focal cerebral ischemia and improves
      deficits of short-term memory and motor coordination after global cerebral
      ischemia. However, many outstanding issues remain elusive regarding the
      protective effects of postconditioning against cerebral ischemia. Future studies
      should further identify parameters that generate the strongest protection for
      postconditioning against cerebral ischemia and should study whether
      postconditioning provides long-term protection. In addition, clarification of the
      underlying protective mechanisms should be pursued. This will certainly enhance
      our understanding of this novel phenomenon and may provide important clues for
      developing pharmacological analogues for stroke treatment.

PMID- 18040850
TI  - Spatial learning and memory in HIV-1 transgenic rats.
AB  - HIV-1 infection of the central nervous system impairs neural, cognitive, and
      behavioral functioning in patients despite antiretroviral therapy. However,
      studying mechanisms underlying HIV-1-related neurological and cognitive
      dysfunction has been limited without an adequate animal model. A novel,
      noninfectious HIV-1 transgenic (HIV-1Tg) rat model was recently created that
      expresses an HIV-1 provirus with a deletion of functional gag and pol genes. This
      HIV-1Tg rat reportedly develops clinical manifestations of human HIV disease and
      thus appears to mimic the persistent infection that results from the presence of
      HIV viral proteins in the host. We evaluated the HIV-1Tg rat model using the
      Morris water maze, a popular paradigm for testing learning and memory deficits in
      rodents. Because of congenital cataracts in HIV-1Tg rats, however, the
      traditional use of visual navigational cues in this paradigm were precluded. We
      first designed a modified Morris water maze and demonstrated that neurologically
      intact rats can effectively learn the water maze in the absence of visual cues
      and in the presence of non-visual navigation cues. We then tested HIV-1Tg rats in
      this modified Morris water maze. These HIV-1Tg rats showed a deficit in learning
      how to swim to the location of the hidden platform but did not show a deficit in
      their memory of the general location of the hidden platform. These results
      suggest that the noninfectious HIV-1Tg rat can be a valid model for the
      behavioral studies of HIV-related neurological dysfunction.

PMID- 18040848
TI  - Toll-like receptors in defense and damage of the central nervous system.
AB  - Members of the Toll-like receptor (TLR) family play critical roles as regulators
      of innate and adaptive immune responses. TLRs function by recognizing diverse
      molecular patterns on the surface of invading pathogens. In the brain, microglial
      cells generate neuroimmune responses through production of proinflammatory
      mediators. The upregulation of cytokines and chemokines in response to microbial
      products and other stimuli has both beneficial and deleterious effects. Emerging
      evidence demonstrates a central role for TLRs expressed on microglia as a pivotal
      factor in generating these neuroimmune responses. Therefore, understanding the
      basis of TLR signaling in producing these responses may provide insights into how
      activated microglia attempt to strike a balance between defense against invading
      pathogens and inflicting irreparable brain damage. These insights may lead to
      innovative therapies for CNS infections and neuroinflammatory diseases based on
      the modulation of microglial cell activation through TLR signaling.

PMID- 18040851
TI  - Evidence for neuromodulation of enteropathogen invasion in the intestinal mucosa.
AB  - The extensively innervated intestinal mucosa encompasses a vast surface exposed
      to an array of potentially infectious microorganisms. We investigated the role of
      enteric nerves in modulating intracellular internalization of a multidrug
      resistant Salmonella typhimurium DT104 field isolate in mucosa-submucosa sheets
      from the porcine ileum, a biomedical model for the human intestine. The effects
      of transmural electrical stimulation and drugs on intracellular internalization
      of Salmonella over 90 min was determined by a gentamicin-resistance assay
      relative to untreated tissues from the same animal serving as controls. The actin
      inhibitor cytochalasin D reduced internalization of Salmonella, and the mucus
      disrupting agent dithiothreitol decreased its mucosal adherence. Transmural
      electrical stimulation increased, and neuronal conduction blockers saxitoxin and
      lidocaine decreased Salmonella internalization in stimulated and unstimulated
      tissues. Furthermore, the alpha-adrenergic/imidazoline receptor ligand
      phentolamine and the 5-HT(3) receptor antagonist tropisetron decreased
      internalization in stimulated tissues. Based on these findings, enteric neural
      activity appears to modulate interactions between the intestinal mucosa and
      pathogenic bacteria.

PMID- 18040852
TI  - Morphine-induced neuroimmunomodulation in murine visceral leishmaniasis: the
      role(s) of cytokines and nitric oxide.
AB  - Opioid modulation of host resistance to infectious diseases is well documented;
      however, not much is known during visceral leishmaniasis (VL). Low doses of
      morphine, administered subcutaneously in Leishmania donovani-infected BALB/c
      mice, on days 0 and +15, significantly (p < 0.05) suppressed (1 mg/kg/day) or
      even sterile-cleared (2 mg/kg/day) the infection; paradoxically, high doses (10
      and 30 mg/kg/day) exacerbated the infection. In vitro, low concentration (1 x 10(
      9) and 1 x 10(-11) M) morphine treatment of L. donovani-infected mouse peritoneal
      macrophages (PM), endowed them with significant (p < 0.05) leishmanicidal
      activity, whereas a high-concentration (1 x 10(-5) M) treatment augmented
      intramacrophage parasite growth. Naloxone pre-treatment of infected-mice (4 mg/kg
      x 2) and of infected-PM (1 x 10(-5) M), blocked only the morphine low
      dose/concentration-induced protective effect. The splenocytes from protected mice
      and morphine low concentration-treated infected-PM, elaborated significantly (p <
      0.05) enhanced levels of interleukin-12, interferon-gamma, tumor necrosis factor
      alpha, granulocyte-macrophage colony-stimulating factor and nitrite in the
      culture medium; a high dose/concentration suppressed their elaboration.
      Curiously, only morphine high dose/concentration-treated infected mice
      splenocytes and infected PM, produced significantly (p < 0.05) increased quantity
      of transforming growth factor-beta1. Aminoguanidine, significantly (p < 0.05)
      blocked the morphine low dose/concentration-induced protective effect, in vivo
      and in vitro. This first study demonstrates dose-dependent biphasic modulatory
      effects of morphine in L. donovani-infected mice and PM, in vitro, apparently via
      nitric oxide-dependent mechanisms. These results thus demonstrate the
      implications of opiate abuse on the efficacy assessment of antileishmanial drugs
      and vaccines, and on the reactivation of latent VL in areas where both drug abuse
      and VL are rampant.

PMID- 18040853
TI  - Low CSF leptin levels are associated with worse learning and memory performance
      in HIV-infected men.
AB  - OBJECTIVE: The main objective of this study was to investigate the association
      between human CSF leptin levels and neuropsychological (NP) performance in the
      setting of HIV infection. We hypothesized that human CSF leptin levels positively
      correlate with NP performance. BACKGROUND: Leptin is an adipocyte-derived hormone
      that influences brain development and function, particularly learning and memory,
      in the mouse model. The extent to which leptin contributes to neurocognitive
      functioning in humans is less clear. METHOD: A cross-sectional evaluation of CSF
      leptin and NP performance was performed. Leptin levels in CSF and serum samples
      from 59 HIV-positive men were measured by ELISA. Comprehensive, standardized NP
      testing was used to determine impairment status in global and specific domains.
      RESULTS: Lower CSF leptin levels and reduced leptin uptake into the central
      nervous system (CNS) correlated with impaired learning and memory performance in
      both univariate and multivariate analyses. In multivariate analyses, lower CSF
      leptin levels and reduced CNS leptin uptake were associated with worse NP
      performance in learning and memory, adjusting for CD4 nadir, antiretroviral
      treatment exposure, and HIV RNA levels in CSF. CONCLUSIONS: Low CSF leptin levels
      are associated with poorer performance in learning and memory among HIV-infected
      men adjusting for usual predictors of HIV-associated neurocognitive impairment.
      This association is consistent with prior in vitro and animal data suggesting
      leptin has a trophic or facilitatory role in the hippocampus, above and beyond
      its role in hypothalamic regulation.

PMID- 18040854
TI  - The glial response to CNS HIV infection includes p53 activation and increased
      expression of p53 target genes.
AB  - HIV-associated dementia (HAD) is a chronic neuroinflammatory disease that remains
      an important clinical problem without available rational treatment. As HIV does
      not infect neurons, the pathogenesis of HAD is thought to be secondary to the
      impact of infected leukocytes, including parenchymal microglia, which can secrete
      inflammatory mediators and viral products that alter the function of surrounding
      uninfected cells. We previously reported that the transcription factor p53
      accumulates in neurons, microglia, and astrocytes of HAD patients. We have also
      shown that microglia from p53-deficient mice fail to induce neurotoxicity in
      response to the HIV coat protein gp120 in a coculture system, supporting the
      hypothesis that p53 plays a pathogenic role in the chronic neuroinflammatory
      component of HIV-associated neurodegeneration. We analyzed the extent and cell
      type specificity of p53 accumulation in subcortical white matter of ten AIDS
      patients that had previously been shown to demonstrate white matter p53
      accumulation. To determine if p53 activation functioned to alter gene expression
      in HAD, cortical tissue sections were also immunolabeled for the p53 target genes
      Bax and p21(WAF1). These studies reveal that microglia, astrocytes, and
      oligodendrocytes all demonstrate p53 activation in response to HIV infection. We
      observed immunoreactivity for both Bax and p21(WAF1) in neurons and glia from
      patients demonstrating elevated p53 immunoreactivity. Our findings demonstrate
      that widespread increased p53 expression is present in HAD. Activation of p53
      mediated pathways in the glia of HAD patients may contribute to the
      neuroinflammatory processes that promote neurodegeneration by inhibiting glial
      proliferation and/or promoting glial cell dysfunction.

PMID- 18040855
TI  - Neuroimmune pharmacology expanding in Asia Pacific rim.

PMID- 18040856
TI  - Endogenous neural stem cells in the adult brain.
AB  - Despite progress in our understanding molecular mechanisms of neuronal cell death
      in many central nervous system (CNS) diseases, widely effective treatments remain
      elusive. Recent studies have shown that neural stem cells (NSCs) are present in
      the subventricular zone (SVZ) lining the lateral ventricles and the subgranular
      zone (SGZ) of the hippocampal dentate gyrus (DG) in adult mouse, rat, nonhuman
      primate, and human brain. Newly generated cells in the SGZ can differentiate into
      mature, functional neurons and integrate into the DG as granule cells, which are
      involved in memory formation. In addition, many CNS diseases can stimulate the
      proliferation of neuronal stem/progenitor cells located in the SVZ and SGZ of the
      adult rodent brain, and the resulting newborn cells migrate into damaged brain
      regions, where they express mature neuronal markers. Therefore, it might be
      possible for damaged cells to be replaced from endogenous neural stem cell pools.
      However, the capacity of self-repair is obviously not enough. Proliferation,
      migration, and neuronal differentiation of endogenous NSCs could be manipulated
      by pharmaceutical tools to reach the adequate benefits for the treatment of CNS
      diseases.

PMID- 18040857
TI  - Stem cell transplantation: a promising therapy for Parkinson's disease.
AB  - Parkinson's disease is one of the most common neurodegenerative diseases caused
      by the loss of dopaminergic neurons in the substantia nigra pars compacta.
      Pharmacological therapies are valuable but suffer from two main drawbacks: side
      effects and loss of efficacy with disease progression. Surgical treatment is no
      better than drugs. Transplantation of embryonic mesencephalic tissue has emerged
      as a therapeutic alternative, but the unstable efficiency and the shortage of
      embryonic donors limit its clinical application. Recent advances in stem cell
      research inspire our hope that stem cell transplantation to replace degenerated
      neurons may be a promising therapy for Parkinson's disease. There are three
      sources of stem cells currently in testing: embryonic stem cells, neural stem
      cells, and mesenchymal stem cells. The stem cell transplantation in the animal
      model of Parkinson's disease proves that it is capable of relieving symptoms and
      restoring damaged brain function. Future stem cell research should focus not only
      on ameliorating the symptoms of Parkinson's disease but also on neuroprotection
      or neurorescue that can favorably modify the natural course and slow the
      progression of the disease.

PMID- 18040858
TI  - Differential expression of CXCL12 and CXCR4 during human fetal neural progenitor
      cell differentiation.
AB  - Stromal cell-derived factor 1 alpha (SDF-1alpha, CXCL12) and its receptor CXCR4
      play an important role in the central nervous system (CNS) development and
      adulthood by mediating cell migration, enhancing precursor cell proliferation,
      assisting in neuronal circuit formation, and possibly regulating migration during
      repair. The expression pattern of CXCR4 and CXCL12 during neurogenesis has not
      been thoroughly elucidated. In this study, we investigated the expression of
      CXCL12 and CXCR4 during neural progenitor cells (NPC) differentiation by
      microarray analysis and reverse transcriptase-polymerase chain reaction (RT-PCR)
      using human fetal NPC as a model system. The production of CXCL12 was measured by
      enzyme-linked immunosorbent assay (ELISA). CXCR4 expression was determined by
      florescence-activated cell sorting (FACS) analysis, immunocytochemical staining,
      and CXCR4-mediated inhibition of cyclic AMP (cAMP) accumulation. Our data
      demonstrated that CXCR4 expression is significantly upregulated when NPC are
      differentiated into neuronal precursors, whereas CXCL12 is upregulated when
      differentiated into astrocytes. We also provide evidence that CXCR4 localization
      changes as neurons mature. In neuronal precursors, CXCR4 is localized in both
      neuronal processes and the cell body, whereas in mature neurons, it is primarily
      expressed on axons and dendrites. This differential expression of CXCR4 and
      CXCL12 may be important for the temporal regulation of neuronal migration and
      circuit formation during development and possibly in adult neurogenesis and
      repair.

PMID- 18040859
TI  - CD200-CD200R regulation of microglia activation in the pathogenesis of
      Parkinson's disease.
AB  - The role of CD200-CD200R signaling in immune regulation of the central nervous
      system has become a popular field of research in recent years. Many studies have
      shown that there is a close correlation between CD200-CD200R, microglia
      activation, and Parkinson's disease (PD). This review discusses the above
      relationship, highlighting (1) the gene mapping and molecular structure of CD200
      and CD200R, (2) the distribution and expression of CD200 and CD200R in the
      nervous system, (3) the effect of CD200-CD200R signaling on microglia activation,
      and (4) the role of microglia activation in the pathogenesis and progression of
      PD. Finally, we discuss the status of current studies on the regulation of
      microglia activation in PD and strongly suggest that it is very promising to
      regulate microglia activation in PD via targeting CD200-CD200R signaling
      pathways.

PMID- 18040860
TI  - Voltage-gated potassium channel modulation of neurotoxic activity in human
      immunodeficiency virus type-1(HIV-1)-infected macrophages.
AB  - Macrophages play an important role in brain immune and inflammatory responses.
      They are also critical cells in mediating the pathology of neurodegenerative
      disorders such as HIV-associated dementia. This is largely through their capacity
      to secrete a variety of bioactive molecules such as cytokines, leading to
      neuronal dysfunction and/or death. Accumulating evidence indicates that voltage
      gated potassium (Kv) channels play a pivotal role in the modulation of macrophage
      proliferation, activation, and secretion. Blockade of Kv channels by specific
      antagonists decreases macrophage cytokine production and ameliorates macrophage
      associated neuronal injury. These results suggest that Kv channels might become a
      potential target for the development of new therapeutic strategies for chronic
      inflammatory diseases.

PMID- 18040861
TI  - NAD+ and NADH in neuronal death.
AB  - Neuronal death is a key pathological event in multiple neurological diseases.
      Increasing evidence has suggested that NAD+ and NADH mediate not only energy
      metabolism and mitochondrial functions, but also calcium homeostasis, aging, and
      cell death. This article is written to provide an overview about the information
      suggesting significant roles of NAD+ and NADH in neuronal death in certain
      neurological diseases. Our latest studies have suggested that intranasal
      administration with NAD+ can profoundly decrease ischemic brain damage. These
      observations suggest that NAD+ administration may be a novel therapeutic strategy
      for some neurological diseases.

PMID- 18040862
TI  - Downregulation of parkin damages antioxidant defenses and enhances proteasome
      inhibition-induced toxicity in PC12 cells.
AB  - Loss-of-function mutations in the parkin gene have recently been shown to be
      responsible for autosomal recessive juvenile Parkinsonism. However, the exact
      mechanism of pathogenesis remains unclear. This study explores the effect of
      Parkin downregulation on dopaminergic cells in Parkinson's disease. We generated
      small interfering RNA plasmids that target the parkin gene and transfected them
      into PC12 cells to mimic in vivo loss-of-function. We found that these small
      plasmids were able to effectively inhibit endogenous Parkin expression in PC12
      cells. Downregulation of Parkin decreased the amount of glutathione and
      superoxide dismutase activity without affecting the amount of malondialdehyde.
      Moreover, Parkin knockdown rendered PC12 cells more susceptible to cell death
      induced by the proteasome inhibitor lactacystin. These results indicate that
      downregulation of Parkin may damage the antioxidation defenses of dopaminergic
      cells and increase their susceptibility to proteasome inhibitor-induced toxicity.

PMID- 18040863
TI  - Therapeutic angiogenesis for brain ischemia: a brief review.
AB  - In the normal mature brain, blood vessel formation is tightly downregulated.
      However, pathologic processes such as ischemia can induce cerebral vascular
      regeneration. Angiogenesis is one of the major styles of new vessel formation. In
      this article, we summarize the major angiogenic factors in the brain, discuss the
      significant changes of angiogenic factors and endothelial progenitor cells (EPCs)
      in response to brain ischemia, and finally, review the therapeutic potential of
      angiogenic factors and EPCs in experimental cerebral ischemia based on the
      concept of neurovascular unit.

PMID- 18040864
TI  - RanBPM, a scaffolding protein in the immune and nervous systems.
AB  - We review the literature for Ran Binding Protein in the Microtubule-Organizing
      Center (RanBPM; RanBP9), a 90-kDa protein that possesses many characteristics of
      a scaffolding protein, including protein-interaction motifs, a cytoskeletal
      binding domain, and multiple canonical docking sites for signaling intermediates.
      We focus on studies that have examined functional interactions between RanBPM and
      other proteins. These studies suggest that RanBPM provides a platform for the
      interaction of a variety of signaling proteins, including cell surface receptors,
      nuclear receptors, nuclear transcription factors, and cytosolic kinases. These
      studies indicate that RanBPM acts as a scaffolding protein and is important in
      regulating cellular function in both the immune system and the nervous system.

PMID- 18040865
TI  - Structure of human insulin monomer in water/acetonitrile solution.
AB  - Here we present evidence that in water/acetonitrile solvent detailed structural
      and dynamic information can be obtained for important proteins that are naturally
      present as oligomers under native conditions. An NMR-derived human insulin
      monomer structure in H2O/CD3CN, 65/35 vol%, pH 3.6 is presented and compared with
      the available X-ray structure of a monomer that forms part of a hexamer (Acta
      Crystallogr. 2003 Sec. D59, 474) and with NMR structures in water and organic
      cosolvent. Detailed analysis using PFGSE NMR, temperature-dependent NMR, dilution
      experiments and CSI proves that the structure is monomeric in the concentration
      and temperature ranges 0.1-3 mM and 10-30 degrees C, respectively. The presence
      of long-range interstrand NOEs, as found in the crystal structure of the monomer,
      provides the evidence for conservation of the tertiary structure. Starting from
      structures calculated by the program CYANA, two different molecular dynamics
      simulated annealing refinement protocols were applied, either using the program
      AMBER in vacuum (AMBER_VC), or including a generalized Born solvent model
      (AMBER_GB).

PMID- 18040866
TI  - Global analysis of gene expression in flower buds of Ms-cd1 Brassica oleracea
      conferring male sterility by using an Arabidopsis microarray.
AB  - The dominant male sterility gene Ms-cd1 is identified in Brassica oleracea.
      Electron microscopical observations revealed that abortion of pollen development
      starts after tetrad formation. This important male sterility phenotype is
      characterized by lack of degradation of the primary pollen mother cell (PMC) wall
      and delayed degradation of callose surrounding the tetrads and thus arrest of
      microspore release. Gene expression of the male sterile and fertile buds was
      analyzed by heterologous hybridization of Brassica oleracea cRNA onto an
      Arabidopsis whole genome oligonucleotide microarray. A total of 277 suppressed
      genes including 40 kinase-, 32 cell wall modification and 29 transport related
      genes were found to be significantly down regulated >3-fold in the male sterile
      mutant. The vast majority of the differentially expressed transcripts are found
      to present late pollen stage specific genes. Kinase genes, cell wall modification
      genes and ion transport genes were greatly over-represented when compared to
      their percentage of all flower bud expressed genes and represent 36.5% of the
      genes suppressed by Ms-cd1. Our results also suggest that Ms-cd1 may blocks an
      anther developmental pathway with a small number of genes suppressed in tapetum
      cells which prevent the degradation of callose and PMC wall, which further leads
      to the suppression of a large number of genes involved in signaling pathways,
      cell wall modification and ion transport in pollen grains.

PMID- 18040867
TI  - New data on the cytology of parthenogenetic weevils (Coleoptera, Curculionidae).
AB  - Parthenogenesis and, in particular, polyploidy are rare in animals. A number of
      cases, known among weevils, represent apomictic parthenogenesis--a reproductive
      mode in which eggs undergo one maturation division, the chromosomes divide
      equationally, and no reduction takes place. Among parthenogenetic weevils there
      are two diploids, 48 triploids, 18 tetraploids, six pentaploids, three hexaploids
      and one decaploid. Eight examined parthenogenetic species are triploids with 33
      chromosomes of different morphology, confirming that triploidy is the most common
      level of ploidy in weevils. The karyotypes are heterogeneous with the presence of
      meta-, submeta-, subtelo- and acrocentric chromosomes. The C-banding method
      showed that only two species possess a large amount of heterochromatin visible as
      a band around the centromere during mitotic metaphase. This agrees with
      observations that weevils are characterized by a small amount of heterochromatin,
      undetectable in metaphase plates after C-banding. In three species an atypical
      course of apomictic oogenesis occurs with stages similar to meiosis, in which
      chromosomes form bivalents and multivalent clusters. This association of
      chromosomes probably represents the remnants of meiosis, although these events
      have nothing to do with recombination. The results support the hypothesis that
      the evolution of apomictic parthenogenesis in weevils has proceeded through a
      stage of automixis.

PMID- 18040868
TI  - A sulfate-reducing bacterium with unusual growing capacity in moderately acidic
      conditions.
AB  - The use of sulfate-reducing bacteria (SRB) is a cost-effective route to treat
      sulfate- contaminated waters and precipitate metals. The isolation and
      characterization of a SRB strain from an AMD in a Brazilian tropical region site
      was carried out. With a moderately acidic pH (5.5), the C.1 strain began its
      growth and with continued growth, modified the pH accordingly. The strain under
      these conditions reduced sulfate at the same rate as an experiment performed
      using an initial pH of 7.0. The dsrB gene-based molecular approach was used for
      the characterization of this strain and its phylogenetic affiliation was similar
      to genus Desulfovibrio sp. The results show an SRB isolate with unexpected
      sulfate reducing capacity in moderately acidic conditions, bringing new
      possibilities for the treatment of AMD, as acid water would be neutralized to a
      mildly acidic condition.

PMID- 18040869
TI  - The population level of Eotetranychus lewisi and the concentration of
      carbohydrates in peach trees.
AB  - Lewis spider mite Eotetranychus lewisi (McGregor) is the most important pest in
      peach orchards, Prunus persica (L.) (Batsch), in North-Central Mexico. In autumn
      2003 and spring 2004, two glasshouse experiments were carried out to assess the
      influence of that mite on the concentration of total soluble sugars and starch in
      leaves, bark and roots of 'diamante mejorado' peach trees. Apical leaves of peach
      trees were inoculated with three mite densities per leaf: (A) 10-20, (B) 21-40,
      (C) 41-80; a mite-free control was added. In 2003, at 81 days after infestation
      (DAI), cumulative mite-days per leaf (CMD) were 153, 1313, 2844 and 4771 in
      control and treatments (A), (B) and (C), respectively. In the same order, these
      CMD caused reductions in total soluble sugars (TSS): in leaves, 45, 50 and 61%;
      in bark, 9, 20 and 33%; in roots, 8, 20 and 26%. Reductions of starch
      concentration in leaves were 17, 43 and 56%; in bark, 25, 55 and 32%; in roots,
      17, 22 and 32%. In 2004, at 77 DAI and 57, 1043, 2426 and 3996 CMD for control
      and treatments (A), (B) and (C), respectively, resulting reductions of TSS were:
      in leaves, 3, 7 and 15%; in bark, 0.8, 3 and 5%; in roots, 57, 60 and 78%,
      whereas reductions in starch concentration were: in leaves, 30, 34 and 44%; in
      bark, 18, 24 and 41%; in roots, 17, 47 and 48%. The higher reductions in roots
      found in 2004 are attributed to cumulative injury affecting food reserves.

PMID- 18040870
TI  - An update on the ecological distribution of Ixodid ticks infesting cattle in
      Rwanda: countrywide cross-sectional survey in the wet and the dry season.
AB  - As part of the epidemiological studies aimed at developing an East Coast fever
      (ECF) immunisation control strategy, which combines an infection and treatment
      method with strategic tick control, a countrywide tick survey was carried out in
      both the dry and the wet season to determine the abundance and the dynamics of
      the tick populations infesting cattle in Rwanda. Six Ixodid tick species where
      identified from a total of 12,814 tick specimens collected. Rhipicephalus
      appendiculatus, the main vector of ECF was the most abundant (91.8%) followed by
      Boophilus decoloratus (6.1%) and Ambyomma variegatum (1.2%). Few ticks from the
      three other less economically important Ixodid species (Rhipicephalus compositus,
      R. evertsi evertsi and Ixodes cavipalpus) were recovered. Both adult and immature
      stages of the most dominant tick species were found to be widespread with a year
      round presence. The numbers of ticks were high in low land and medium zones and
      declined markedly in the higher regions of Rwanda. The geographical distribution
      of various tick species throughout the country and their epidemiological
      implications are discussed.

PMID- 18040871
TI  - Serotonin-like immunoreactivity in the central nervous system of two ixodid tick
      species.
AB  - Immunocytochemistry was used to describe the distribution of serotonin-like
      immunoreactive (5HT-IR) neurons and neuronal processes in the central nervous
      system (CNS), the synganglion, of two ixodid tick species; the winter tick,
      Dermacentor albipictus and the lone star tick, Amblyomma americanum. 5HT-IR
      neurons were identified in the synganglion of both tick species. D. albipictus
      had a significantly higher number of 5HT-IR neurons than A. americanum. The
      labeling pattern and number of 5HT-IR neurons were significantly different
      between sexes in D. albipictus, but were not significantly different between
      sexes in A. americanum. 5HT-IR neurons that were located in the cortex of the
      synganglion projected processes into the neuropils, invading neuromeres in the
      supraesophageal ganglion including the protocerebrum, postero-dorsal, antero
      dorsal and cheliceral neuromeres. In the subesophageal ganglion, dense 5HT-IR
      neuronal processes were found in the olfactory lobes, pedal, and opisthosomal
      neuromeres. Double-labeling with neurobiotin backfilled from the first leg
      damaged at the Haller's organ revealed serotoninergic neuronal processes
      surrounding the glomeruli in the olfactory lobes. The high number of the 5HT-IR
      neurons and the extensive neuronal processes present in various regions of the
      synganglion suggest that serotonin plays a significant role in tick physiology.

PMID- 18040872
TI  - Unusual findings on host-tick interactions through carnivore scat analysis.
AB  - In the course of a study on the diet of two Portuguese carnivores, the red fox
      (Vulpes vulpes Linnaeus) and the common genet (Genetta genetta Linnaeus), 276
      ticks were found inside the 940 scats analyzed. Prevalence in samples was 7.6%
      for both predators. Association of ticks with prey identified on scats, resulted
      in new data for Portugal on host-tick interactions [e.g. Ixodes acuminatus
      (Neumann, 1901) and wood mouse] and tick distribution pattern. These unusual
      findings, besides shedding some light on the host-tick Portuguese assemblage,
      revealed scats as a new source of biological information.

PMID- 18040873
TI  - Near-infrared spectroscopy to monitor peripheral blood flow perfusion.
AB  - BACKGROUND: Non-invasive evaluation of peripheral perfusion may be useful in many
      contexts including peri-operative monitoring. We validated a novel non-invasive
      spectroscopy technique to assess peripheral perfusion. This method, which is
      based on the measurement of tissue saturation variations after an ischemic
      period, was compared to strain gauge plethysmography and radionuclide
      plethysmography. The technique uses near-infrared spectroscopy (NIRS) to
      determine the rate of change of forearm tissue saturation during reactive
      hyperemia. METHODS: In a prospective crossover study, 25 subjects were
      simultaneously evaluated with NIRS and strain gauge plethysmography. Six baseline
      flow measurements were performed to assess the reproducibility of each method.
      Twenty-seven serial measurements were then made to evaluate flow variation during
      forearm reactive hyperemia. RESULTS: Strain gauge and NIRS methods showed
      excellent reproducibility with intra-class correlation coefficients of 0.96 and
      0.93, respectively. CONCLUSION: The NIRS technique appears well suited for the
      non-invasive evaluation of limb perfusion.

PMID- 18040874
TI  - Comet Assay measurements: a perspective.
AB  - The Comet Assay or single cell gel electrophoresis assay is one of the very
      widely used assays to microscopically detect DNA damage at the level of a single
      cell. The determination of damage is carried out either through visual scoring of
      cells (after classification into different categories on the basis of tail length
      and shape) or by using different commercially available or public domain software
      (which automatically recognise the extent of damage). In this assay, the shape,
      size and amount of DNA within the 'comet' play important roles in the
      determination of the level of damage. The use of a software in particular also
      provides a range of different parameters, many of which might not be relevant in
      determining the extent of DNA damage. As a large number of factors could
      influence the shape, size, identification and determination of induced damage,
      which includes the scoring criteria, staining techniques, selection of parameters
      (whilst using the software packages) and appearance of 'hedgehog' or 'clouds',
      this article aims (a) to provide an overview of evolution of measurements of DNA
      damage using the Comet Assay and (b) to summarise and critically analyse the
      advantages and disadvantages of different approaches currently being adopted
      whilst using this assay. It is suggested that judicious selection of different
      parameters, staining methods along with inter-laboratory validation and
      harmonisation of methodologies will further help in making this assay more robust
      and widely acceptable for scientific as well as regulatory studies.

PMID- 18040875
TI  - UV radiation exposure, skin type and lymphoid malignancies: results of a French
      case-control study.
AB  - OBJECTIVES: Investigating the relationship between skin type, UV exposure, and
      lymphoid malignancies (LM). METHODS: We conducted a hospital-based case-control
      study in France, including 813 incident cases of non-Hodgkin's lymphoma (NHL),
      Hodgkin's lymphoma (HL), lymphoproliferative syndrome (LPS) or multiple myeloma
      and 748 controls. RESULTS: Positive associations between HL and blond/red hair
      (OR = 1.8 [0.8-3.8]), very fair/fair skin (OR = 1.6 [1.0-2.5]) were observed.
      High propensity to burn was associated with HL (OR = 1.5 [1.0-2.2]) and LPS (OR =
      1.4 [1.0-2.1]). Poor ability to tan was significantly associated with HL (OR =
      1.7 [1.0-2.8]). Having light hair with high propensity to burn was associated
      with NHL (OR = 1.5 [0.9-2.5]) and significantly with HL (OR = 3.4 [1.4-8.4]).
      Having dark hair with high propensity to burn was significantly associated with
      LPS (OR = 1.5 [1.0-2.2]). The associations with HL and NHL were significant for
      men only, with significant interactions. Outdoors activities since leaving school
      or in the last decade were not related to LM. Only an almost negative trend was
      observed. Prior exposure to artificial UV was not associated with LM. CONCLUSION:
      These results suggest a positive association between the most reactive and palest
      skin types and NHL or HL in men and do not rule out a slight negative
      relationship between UV exposure and LM.

PMID- 18040876
TI  - Afforestation areas defined by GIS in Golbasi specially protected area
      Ankara/Turkey.
AB  - This paper concentrates on determining the areas for afforestation and the
      development of conservation strategies and actions in the case where there is
      high demand for the conservation of a particular land area. The analysis of
      hydrological landscape structure and of erodibility was prerequisite in the
      methodological design considering the site-specific natural landscape
      characteristics of the study area. The Golbasi Specially Protected Area (SPA)
      being the case area has many local environmental disturbances, especially with
      respect to its hydrological system, and the area is beset by increasing demands
      for its use by the burgeoning human population. It is obviously clear that the
      present intensive demand for recreational use will be forecasted further increase
      in the future. The count of rural residences is estimated to increase by 50% over
      the next decade. This intensive demand shall further strain the carrying capacity
      of the ecological milieu, which has already suffered to a significant degree
      because of the present urban and rural activities. The Golbasi district is
      located only 20 km from the city center of Ankara, and its surroundings were
      legally designated to be a Specially Protected Area primarily for the existence
      of lacustral and fluvial systems where two interconnected lakes exist: Mogan and
      Egmir Lakes. Essentially, the continuity of the lacustral and fluvial system of
      Lakes Mogan and Egmir depends on the preservation and improvement of the water
      sources. However, interconnected surface water bodies of these lakes are actually
      quite contaminated, and a decline in the water flow from Mogan to Egmir has been
      observed. For the elaboration of the present method, required conventional maps
      (at 1/25,000 scale) of topography (for slope analysis) and geology (for
      erodibility and permeability analysis) were transferred to computer media using
      AutoCAD R.14 software. The rectification of the transferred data was done using
      ERDAS Imagine 8.3. All data were then transferred into a GIS engine (Arcview
      3.2). This software provided the ability to create, manipulate, analyze and
      display topologically correct geographic data in digital form. The method
      proceeded according to the following phases: 1. Analysis of the hydrologic
      landscape structure; 2. Permeability of the soil structure; 3. Permeability of
      the geological structure; 4. Conservation zones.

PMID- 18040877
TI  - Exposure assessment of fishes to a modern pulp and paper mill effluents after a
      black liquor spill.
AB  - Conjugated resin acids (RAs) in fish bile are considered a sensitive chemical
      indicator of exposure to pulp and paper mill effluent, and were used in this
      study to monitor the post-spill situation of a lake area (Southern Lake Saimaa)
      contaminated by black liquor discharged from a mill in June 2003. From the
      exposure perspective of populations of wild roach and perch, which were studied
      for their bile RAs at four time periods (July 2003, September 2003, May 2004,
      July 2004), the exceptional event passed in 2 months or less. Perch had lower
      concentration of RAs in bile than roach in all sampling areas and all times.
      Besides the current emissions present in the water column, part of the exposure
      status of the roach population to RAs seemed to derive from historically
      contaminated sediments. In order to test this hypothesis, a laboratory experiment
      with perch and roach, along with three teleosts (rainbow trout, brown trout and
      whitefish), was conducted. The species were simultaneously exposed for 7 days to
      RAs (23 microg/l). We calculated a perch/roach-ratio to investigate the
      difference in origin of exposure between perch and roach populations in the wild
      and in the laboratory. One year after the spill, the perch/roach-ratio of bile
      RAs was 0.25 (CV 25%) at 1 km from the mill. This is in contrast to that found
      under the sole waterborne conditions (0.44; CV 24%), supporting the idea that
      sediments serve as an additional source of RAs in roach. Additionally,
      bioconcentration factor log BCF(bile(RA)) was calculated to assess hepatobiliary
      performance and the capacity to excrete RAs in fish.

PMID- 18040878
TI  - Heavy metals in two fish species (Carangoidel malabaricus and Belone stronglurus)
      from Pulicat Lake, North of Chennai, Southeast Coast of India.
AB  - We present the results from a detailed study based on five metals (Cr, Cd, Zn, Pb
      and Fe) measured in four organs (gills, liver, intestine and muscle) of two fish
      species (Carangoidel malabaricus and Belone stronglurus) from Pulicat Lake in
      southeast coast of India. The results show marked differences between the two
      species and organs as well as significant variations within the five analyzed
      metals. Although the metal concentrations measured in fish muscle are low, high
      levels of Pb and Fe were observed in the liver and gills of the two fish species.
      The concentrations of heavy metals in edible parts (muscle) of fish were within
      the permissible levels and are safe for the human consumption.

PMID- 18040879
TI  - Is PM(10) mass measurement a reliable index for air quality assessment? An
      environmental study in a geographical area of north-eastern Italy.
AB  - The aim of this study was to measure the concentration of some metals (Cd, Cr,
      Cu, Fe, Mn, Ni, Pb, and Ti) in PM(10) samples collected in one urban and one
      industrial site and to assess that PM(10) total mass measurement may be not
      sufficient as air quality index due to its complex composition. Metals were
      determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES)
      and differential pulsed anodic stripping voltammetry (DPASV). The measured
      concentrations were used to calculate the content of metals in the PM(10) total
      mass, and to estimate the enrichment factors and the correlations between PM(10),
      metal concentrations and meteorological data for the two sites. The mean PM10
      concentration during the sampling period in the urban site exceeded the annual
      European Union (EU) standard (40 microg/m(3)) and, for some sampling days, the
      daily EU standard (50 microg/m(3)) was also exceeded. In opposite, both EU
      standards were never exceeded in the industrial site. The overall metal content
      was nearly double in the industrial site compared to the urban one, and the mean
      Ni concentration exceeded the EU annual limit value (10 ng/m(3)). The metals with
      the highest enrichment factor were Cd, Cu, Ni and Pb for both sites, suggesting a
      dominant anthropogenic source for these metals. Metal concentrations were very
      low and typical of rural background during Christmas holidays, when factories
      were closed. PM(10) total mass measurement is not a sufficient air quality index
      since the metal content of PM(10) is not related to its total mass, especially in
      sites with industrial activities. This measurement should be associated with the
      analysis of toxic metals.

PMID- 18040880
TI  - Problems caused by land-misuse; the sample of Erzurum.
AB  - In especially urban areas and their proximity, environmental pollution has
      reached a level which threatens both people and public health. Although
      environmental problems in Turkey have been studied for many cities, including
      Erzurum, no study is present combining all the environmental matters of the city
      with short definitions of problems it faces, therefore, this study attempts to
      reveal the definition of the scope and problem of pollution and land use problems
      in Erzurum and use of studies from developing cities elsewhere in the world for
      comparison of methods and solutions.

PMID- 18040884
TI  - Health-related quality of life (HRQoL) domains most valued by urban isiXhosa
      speaking people.
AB  - PURPOSE: The aim of the study was to investigate and identify aspects of health
      related quality of life (HRQoL) that are most valued by isiXhosa-speaking people
      resident in under-resourced areas of Cape Town. METHODOLOGY: Fifty-seven domains
      of HRQoL were identified as important through group discussions with isiXhosa
      speaking people. Participants randomly selected from the community (n = 601) and
      from individuals seeking medical attention at a local clinic (n = 102) graded the
      domains on a visual analogue scale (VAS) ranging from 0 as "not at all important"
      to 10 as " very important". The domains were then mapped to the categories of the
      International Classification of Functioning, Disability, and Health. RESULTS: The
      domains regarded as being most important were food availability (9.5, SD = 1.52),
      owning a brick house (9.4, SD = 1.57), access to medical services (9.4, SD =
      1.55), and family safety (9.4, SD = 1.7). Having no bodily pain was ranked 40th.
      Environmental factors were valued significantly more than the other two
      categories and those related to body functions were valued more highly than
      domains in the category of activity/participation. DISCUSSION AND CONCLUSION:
      Despite being asked specifically to answer the questions in relation to their
      health status, the participants apparently did not differentiate between general
      quality of life (QoL) and specific HRQoL. It appears that members of an under
      resourced community regard socioeconomic and service delivery aspects of their
      lives as integral to their perceived state of health. It may be that it is not
      possible to separate factors relating to general quality of life from those
      specifically related to HRQoL in an under-resourced population and such
      populations might not be suitable for inclusion in certain clinical trials where
      improvement in HRQoL is the required outcome. Alternatively, if a HRQoL
      instrument is to be used to monitor the impact of medical intervention, the
      inclusion of environmental factors should be considered.

PMID- 18040883
TI  - Impact of prevalent and incident vertebral fractures on utility: results from a
      patient-based and a population-based sample.
AB  - Data are scarce on the impact of vertebral fractures (VFX) on utility. The
      objective of this study was to assess the impact of prevalent and incident VFX on
      utility in both a patient-based and population-based sample. Data from the
      Multiple Outcomes of Raloxifene Evaluation (MORE) study (n = 550 for prevalent
      VFX and n = 174 for incident VFX) and the European Prospective Osteoporosis Study
      (EPOS) (n = 236) were used. Utility was assessed by the index score of the EQ-5D.
      In the MORE study, highly statistically significant associations were found
      between utility and the presence of prevalent VFX (p < 0.001), number of
      prevalent VFX (p < 0.001), severity of prevalent VFX (p < 0.001), the combination
      of number and severity of prevalent VFX (p = 0.001) and location of prevalent VFX
      (p = 0.019). The mean utility was significantly lower among women who suffered an
      incident VFX (utility = 0.67) than among women who did not (utility = 0.77) (p =
      0.005), although utility loss was not significantly different between the two
      groups (p = 0.142). In EPOS, the combination of number and severity of incident
      VFX was significantly related to utility (p = 0.030). In conclusion, utility is
      lower among persons with prevalent and incident VFX, especially in a patient
      based sample. Utility loss was not significantly different between women without
      and with incident VFX.

PMID- 18040885
TI  - Some thoughts on the 2007 World Conference on Research Integrity.

PMID- 18040887
TI  - Noninvasive method for simultaneously measuring the thermophysical properties and
      blood perfusion in cylindrically shaped living tissues.
AB  - An easy-to-use noninvasive method was developed to simultaneously measure the
      thermophysical parameters and blood perfusion in cylindrically shaped living
      tissues. This method is based on a two-dimensional mathematical model which
      requires temperature measurements at only three separate points along the axial
      direction on the cylinder surface. A sensitivity analysis has shown that the key
      thermophysical parameters, such as the thermal conductivity, volumetric heat
      capacity, and blood perfusion can be estimated simultaneously with high accuracy.
      Genetic algorithm (GA) selection, crossover, and mutation operators were
      developed to solve this multi-parameter optimization problem. This three-point
      method was validated by measuring the properties of a dynamic tissue-equivalent
      phantom with known thermal parameters. The method has also been applied to
      measure the thermophysical parameters and blood perfusion in human forearms with
      measured results agreeing well with the literature values.

PMID- 18040886
TI  - L-arginine metabolism and its impact on host immunity against Leishmania
      infection.
AB  - Leishmaniasis is a vector-borne disease found in many countries worldwide. The
      causative agent of the disease, Leishmania spp., lives as an obligate
      intracellular parasite within mammalian hosts. Since tissue macrophages are major
      target cells for parasite replication, the outcome of infection depends largely
      on the activation status of these cells. L-arginine is a crucial amino acid
      required for both nitric oxide (NO)-mediated parasite killing and polyamine
      mediated parasite replication. This review highlights the significance of L
      arginine as a factor determining the outcomes of Leishmania infection in vitro
      and its influences on host immune responses in vivo. Various therapeutic
      approaches targeting L-arginine metabolic pathways during infections with
      Leishmania are also discussed.

PMID- 18040889
TI  - International neurocritical care: report from the Costa Rica Neurointensive and
      Neuromonitoring Course.

PMID- 18040890
TI  - Inverse current-source density method in 3D: reconstruction fidelity, boundary
      effects, and influence of distant sources.
AB  - Estimation of the continuous current-source density in bulk tissue from a finite
      set of electrode measurements is a daunting task. Here we present a methodology
      which allows such a reconstruction by generalizing the one-dimensional inverse
      CSD method. The idea is to assume a particular plausible form of CSD within a
      class described by a number of parameters which can be estimated from available
      data, for example a set of cubic splines in 3D spanned on a fixed grid of the
      same size as the set of measurements. To avoid specificity of particular choice
      of reconstruction grid we add random jitter to the points positions and show that
      it leads to a correct reconstruction. We propose different ways of improving the
      quality of reconstruction which take into account the sources located outside the
      recording region through appropriate boundary treatment. The efficiency of the
      traditional CSD and variants of inverse CSD methods is compared using several
      fidelity measures on different test data to investigate when one of the methods
      is superior to the others. The methods are illustrated with reconstructions of
      CSD from potentials evoked by stimulation of a bunch of whiskers recorded in a
      slab of the rat forebrain on a grid of 4x5x7 positions.

PMID- 18040888
TI  - Neuroprotective role of antidiabetic drug metformin against apoptotic cell death
      in primary cortical neurons.
AB  - Oxidative damage has been reported to be involved in the pathogenesis of diabetic
      neuropathy and neurodegenerative diseases. Recent evidence suggests that the
      antidiabetic drug metformin prevents oxidative stress-related cellular death in
      non-neuronal cell lines. In this report, we point to the direct neuroprotective
      effect of metformin, using the etoposide-induced cell death model. The exposure
      of intact primary neurons to this cytotoxic insult induced permeability
      transition pore (PTP) opening, the dissipation of mitochondrial membrane
      potential (DeltaPsim), cytochrome c release, and subsequent death. More
      importantly, metformin, together with the PTP classical inhibitor cyclosporin A
      (CsA), strongly mitigated the activation of this apoptotic cascade. Furthermore,
      the general antioxidant N-acetyl-L: -cysteine also prevented etoposide-promoted
      neuronal death. In addition, metformin was shown to delay CsA-sensitive PTP
      opening in permeabilized neurons, as triggered by a calcium overload, probably
      through its mild inhibitory effect on the respiratory chain complex I. We
      conclude that (1) etoposide-induced neuronal death is partly attributable to PTP
      opening and the disruption of DeltaPsim, in association with the emergence of
      oxidative stress, and (2) metformin inhibits this PTP opening-driven commitment
      to death. We thus propose that metformin, beyond its antihyperglycemic role, can
      also function as a new therapeutic tool for diabetes-associated neurodegenerative
      disorders.

PMID- 18040891
TI  - Dexamethasone-induced suppression of steroidogenic acute regulatory protein gene
      expression in mouse Y-1 adrenocortical cells is associated with reduced histone
      H3 acetylation.
AB  - In this study, we investigated the effect of dexamethasone on the expression of
      steroidogenic acute regulatory protein (StAR) and the acetylation of histone H3
      in mouse Y-1 adrenocortical tumor cells. Treatment of Y-1 cells with increasing
      concentrations (0.001-50 microg/ml) of dexamethasone for 24 h suppressed 8-Br
      cAMP (0.5 mM)-stimulated StAR mRNA and protein levels and progesterone production
      in a dose-dependent manner. Treatment of Y-1 cells with 8-Br-cAMP (0.5 mM) for 1
      24 h resulted in a marked increase in StAR mRNA levels. This increase was
      associated with an increase in progesterone production. StAR mRNA was down
      regulated by dexamethasone at times greater than 3 h. To evaluate dexamethasone
      effect on the endogenous StAR gene, chromatin immunoprecipitation assays were
      performed in combination with polymerase chain reaction. 8-Br-cAMP increased
      histone H3 acetylation within the proximal region of the StAR gene promoter and
      coincubation with dexamethasone blocked this effect. Dexamethasone had no effect
      on glucocorticoid receptor mRNA expression. These results demonstrate that
      dexamethasone repression of 8-Br-cAMP-stimulated StAR gene expression in Y-1
      cells is accompanied by reductions in histone H3 acetylation associated with the
      StAR gene promoter.

PMID- 18040892
TI  - Carbamylcholine and ouabain effects on Ca2+ handling and insulin release in
      islets from rats depleted in long-chain polyunsaturated omega 3 fatty acids.
AB  - A number of metabolic, ionic and secretory variables were recently found to be
      affected in pancreatic islets obtained from second generation rats depleted in
      long-chain polyunsaturated omega 3 fatty acids (omega 3 rats). The present study
      further documents three sets of anomalies in such islets. First, after 90 min
      exposure to D-glucose (8.3 mM), the release of insulin from perifused islets,
      prelabelled with 45Ca, is lower in omega 3 rats than in control animals, despite
      comparable 45Ca fractional outflow rate. Second, over 15 min exposure to
      carbamylcholine (0.1 mM), in the presence of D: -glucose, the cytosolic
      concentration of Ca2+ is increased to a greater relative extent in dispersed
      islet cells from omega 3 rats, as compared to control animals. This coincides
      with a greater relative increase in insulin output from perifused islets during
      the second phase of the secretory response to the cholinergic agent. Last, the
      increase provoked by ouabain (1.0 mM) in cytosolic Ca2+ concentration, 45Ca
      fractional outflow rate and insulin release are all delayed in the omega 3 rats.
      Taking into account the decreased activity of Na+, K+-ATPase in the islets of
      omega 3 rats, these findings are interpreted as reflecting an impaired priming of
      insulin-producing cells when first exposed for 105 min to a physiological
      postprandial concentration of D-glucose.

PMID- 18040893
TI  - The aldosterone to renin ratio in the evaluation of patients with incidentally
      detected adrenal masses.
AB  - Incidentally discovered adrenal masses are diagnosed with increasing frequency,
      especially among patients with hypertension. Thus, a reliable screening test for
      primary hyperaldosteronism (PA) is essential to avoid unnecessary diagnostic
      procedures to this population. The aim of the present study is the evaluation of
      aldosterone to renin ratio (ARR), using plasma renin concentration, in the
      diagnostic algorithm of patients with adrenal incidentaloma. A total of 123
      individuals were studied: 17 patients with proven PA (age 55.5 +/- 1.4 years), 27
      patients with nonfunctioning adrenal incidentaloma (age 60.3 +/- 1.8 years, 14
      hypertensives and 13 normotensives) and 79 control subjects (age 58.7 +/- 1.4
      years, 27 hypertensives and 52 normotensives). A receiver operating
      characteristic (ROC) analysis disclosed that an ARR > or =32 combines a
      sensitivity of 100% with a specificity of 96.2% for the diagnosis of PA. No
      difference in AlphaRR between hypertensive and normotensive individuals
      harbouring an adrenal incidentaloma and hypertensive and normotensive controls
      was found. Patients with adrenal incidentalomas with subtle glucocorticoid
      hypersecretion demonstrated similar ARR compared to patients with normal cortisol
      secretion. In conclusion, ARR is reliable for the exclusion of PA in patients
      with adrenal incidentalomas. Furthermore, subtle aldosterone hypersecretion, as
      indicated by increased ARR, in patients with adrenal incidentalomas is not
      associated with the presence of hypertension or subtle glucocorticoid
      hypersecretion.

PMID- 18040894
TI  - Expression and localization of cystic fibrosis transmembrane conductance
      regulator in the rat endocrine pancreas.
AB  - Impaired glucose tolerance and overt diabetes mellitus are becoming increasingly
      common complications of cystic fibrosis (CF), most probably merely as a result of
      increased life expectancy. In order to understand the pathophysiology of cystic
      fibrosis-related diabetes (CFRD), knowledge on the possible expression and cell
      distribution of the cystic fibrosis transmembrane conductance regulator (CFTR)
      protein within the endocrine pancreas is required. In this report, we establish
      the first evidence for expression of CFTR protein in rat pancreatic islets by
      using independent techniques. First reverse transcriptase-polymerase chain
      reaction (RT-PCR) amplification showed that CFTR mRNA is present in isolated
      islets of Langerhans. Furthermore, the analysis of flow cytometry-separated islet
      cells indicated that the level of CFTR transcripts is significantly higher in the
      non-beta than in beta-cell populations. The expression of CFTR protein in rat
      islet cells was also demonstrated by Western blotting and the level of expression
      was also found significantly higher in the non-beta than in beta-cell
      populations. Last, in situ immunocytochemistry studies with two monoclonal
      antibodies recognizing different CFTR epitopes indicated that CFTR expression
      occurs mainly in glucagon-secreting alpha-cells.

PMID- 18040895
TI  - Insulin regulation of growth hormone receptor gene expression: involvement of
      both the PI-3 kinase and MEK/ERK signaling pathways.
AB  - The mechanism(s) of insulin's effects on growth hormone receptor (GHR) gene
      expression are poorly understood. Using rat hepatoma cells, we have previously
      shown that insulin treatment reduces GHR mRNA and protein in a time- and
      concentration-dependent manner, at least in part via down-regulation of GHR
      transcription. The present study determines whether the phosphatidylinositol-3
      kinase (PI-3 kinase) and mitogen activated protein kinase kinase
      (MEK)/extracellular signal-regulated kinase (ERK) pathways are involved in
      mediating these effects of insulin. Inhibition of the PI-3 kinase pathway
      partially blocked insulin's reduction of GHR mRNA, as did inhibition of the
      MEK/ERK pathway, resulting in higher GHR mRNA levels. Inhibition of both pathways
      was necessary to completely block insulin effects. Similar results were obtained
      for GHR protein. Collectively, these data suggest that insulin signaling via
      either the PI-3 kinase or MEK/ERK pathway may result in partial reduction of GHR
      gene expression, whereas signaling via both pathways may be required to achieve
      the full insulin effect.

PMID- 18040897
TI  - Comparative study of Bacillus thuringiensis Cry1Aa and Cry1Ac delta-endotoxin
      activation, inactivation and in situ histopathological effect in Ephestia
      kuehniella (Lepidoptera: Pyralidae).
AB  - A comparative study of different steps in the mode of action of the individual
      Bacillus thuringiensis kurstaki BNS3 Cry1Aa and Cry1Ac delta-endotoxins on E.
      kuehniella larvae was performed in order to investigate the origin of the
      difference in the response of this larvae to each of the latter. Proteolytic
      activation was shown to be one of the main steps impaired in E. kuehniella
      tolerance to Cry1Aa. The absence of two proteinase activities as well as an
      altered activity level observed in the case of Cry1Aa would be the consequence of
      proteinase-mediated tolerance of E. kuehniella to this toxin. In situ binding and
      histopathological effect analyses allowed concluding that the binding of the
      toxin to BBMV receptors is the key step in E. kuehniella tolerance to Cry1Aa
      toxin. The latter was slightly bound to apical membranes of epithelial cells that
      remained intact, whereas Cry1Ac was tightly bound to completely damaged cells
      basal membranes.

PMID- 18040896
TI  - Role of the GH/IGF-I axis in the growth retardation of weaver mice.
AB  - IGF-I is a well-established anabolic growth factor essential for growth and
      development. Although the role of the GH/IGF-I axis is established for normal
      postnatal growth, its functional state in neurodegenerative diseases is not fully
      characterized. The weaver mutant mouse is a commonly used model for studying
      hereditary cerebellar ataxia and provides an opportunity to investigate the
      function of IGF-I in postnatal growth following neurodegeneration. Previously, we
      reported that weaver mice are growth retarded and their body weights correlate
      with a decrease in circulating IGF-I levels. Because weaver mice have the same
      food intake/body weight ratios as their wild type littermates, our observation
      suggests that an impairment of the GH/IGF-I axis, rather than poor nutrition,
      likely contributes to their growth retardation. This study further investigated
      the etiology of reduced circulating IGF-I levels. We found that GH levels in
      weaver mice were reduced following acute insulin injection, but the hepatic GH
      receptor transduction pathway signaled normally as evidenced by increased STAT5b
      phosphorylation and IGF-I mRNA levels in response to acute GH administration. In
      addition, 2-week GH treatment induced a significant increase in body weight and
      circulating IGF-I levels in homozygous weaver mice but not in wild type
      littermates. In summary, a deficiency in the GH/IGF-I axis may be partially
      responsible for postnatal growth retardation in weaver mutant mice. This
      deficiency may occur at the level of the pituitary and/or hypothalamus and can be
      improved with GH administration.

PMID- 18040898
TI  - Optimization of the AT-content of codons immediately downstream of the initiation
      codon and evaluation of culture conditions for high-level expression of
      recombinant human G-CSF in Escherichia coli.
AB  - Enhanced therapeutic importance of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) has encouraged us to develop a processing method for
      its high-level expression in E. coli. In this study, we established a high
      yielding clone by incorporation of silent mutations at N-terminal region of human
      G-CSF gene. We studied and optimized various parameters of culture conditions
      connected with the expression of rhG-CSF. The maximum expression was obtained in
      a defined medium supplemented with 1% glucose. The gene in pET-3a vector in E.
      coli BL21 (DE3) PLysS host strain was induced with 2 mM isopropyl beta-D: -1
      thiogalacto pyronoside. The cell growth and productivity was enhanced about 1.6-
      and 1.5-folds, respectively when inducing the culture at OD(600) value of 6 than
      2. The protein expression was significantly increased by addition of rifampicin
      at concentration of 200 microg/ml. The AT content of 51.8% with suitable codon
      sequences at N-terminal region and the concentration of rifampicin were
      identified as the key factors with a significant impact on protein expression.
      The specific productivity of 104 mg/OD/l (68.7% of total cellular protein) of rhG
      CSF was obtained toward the end of the study, which is almost 1.5 times higher
      yield than reported so far in the literature.

PMID- 18040900
TI  - Diagnostic value of magnetic resonance imaging and scintigraphy in patients with
      metastatic breast cancer of the axial skeleton: a comparative study.
AB  - PURPOSE: The goal of this study was to compare the sensitivity of MRI and
      scintigraphy for detecting metastatic bone disease involving the axial skeleton.
      PATIENTS AND METHODS: A total of 59 patients (58 women and 1 man, age range 28-83
      years, mean age 53.0 years) with histopathologically proven breast cancer during
      a 15-month period (between April 2003 and January 2004) were included in the
      study. All the patients underwent scintigraphy and MRI examinations for staging,
      follow-up, or evaluation of bone pain. RESULTS: MR imaging revealed 59 metastases
      in 59 patients (sensitivity, 95%; specificity, 100%; positive predictive value,
      100%). Four lesions detected by MRI were classified as of uncertain origin (grade
      2) and 36 lesions were regarded as definitely benign (grade 1). Scintigraphy
      revealed 44 metastases in 59 patients (sensitivity, 70%; specificity, 94%;
      positive predictive value, 95%). A total of 29 lesions were considered as of
      uncertain origin (grade 2), and 26 lesions were regarded as definitely benign
      (grade 1). About five lesions were graded as grade 2 in scintigraphy, while MRI
      graded them as degeneration or benign compression (Grade 1). For 11 lesions the
      same grade was regarded in both MRI and scintigraphy. Two lesions graded as grade
      3, and eleven lesions graded as grade 2 in scintigraphy demonstrated no
      pathological signal intensity in MRI. In total, 18 lesions with no activity in
      scintigraphy were graded as grade 3 lesions in MRI. CONCLUSION: MRI is more
      sensitive than scintigraphy in the detection of bone metastases. MRI appears to
      be able to screen patients more effectively than scintigraphy if the spine and
      pelvis are included because metastases merely outside the axial skeleton are
      rare.

PMID- 18040901
TI  - Primary non-hodgkin lymphoma of urinary bladder with nine years later renal
      involvement and absence of systemic lymphoma: a case report.
AB  - AIMS: Primary bladder non-Hodgkin lymphoma (PBNHL) is very rare, especially as
      extranodal B-small lymphocytic lymphoma (B-SLL). Also, late isolated renal
      manifestation of PBNHL is extremely unusual. We report a very rare type of
      extranodal B-SLL of bladder wall with extremely unusual late isolated renal
      involvement, clinically manifested by nephrotic syndrome and incipient renal
      failure. A CASE REPORT: A 56-year-old woman was presented with a solitary tumor
      of bladder wall, with history of dysuria and night sweating. A transvaginal
      needle biopsy of the tumor was performed, and diagnosis of primary extranodal B
      SLL was made in the absence of bone marrow, lymph node, or blood involvement. She
      was treated with chemotherapy until the achievement of complete remission. Nine
      years later, she developed nephrotic syndrome. The renal biopsy revealed
      parenchymal lymphoma's involvement associated with glomerular lesion.
      Immunohistochemical analysis confirmed the same imunophenotype of lymphoma cells
      like in bladder wall nine years ago. Restaging procedure showed no evidence of
      disease elsewhere. CONCLUSION: To our knowledge, it is the first case of
      association of very rare primary bladder B-SLL with late isolated renal
      involvement.

PMID- 18040899
TI  - Unusual presentation of metastatic hepatocellular carcinoma in the nasal septum:
      a case report and review of the literature.
AB  - Hepatocellular carcinoma with sinonasal metastasis is extremely rare. We report a
      case of a 49-year-old man who had a history of synchronous hepatocellular
      carcinoma and verrucous carcinoma of tongue. A painless and non-bleeding mass was
      found in the left nasal septum 16 months after hepatocellular carcinoma was
      diagnosed. On computed tomography, the mass was enhanced with contrast. It was
      resected and proved to be metastatic hepatocellular carcinoma. The patient was
      treated with radiotherapy to the nasal area and then with chemotherapy. He was
      still alive, 15 months after the appearance of the nasal metastasis.

PMID- 18040902
TI  - Acute lymphoblastic leukemia during gestation.
AB  - The management of the common acute lymphoblastic leukemia in pregnancy has been
      controversial, but currently aggressive chemotherapy is the practice trend
      worldwide. We treated a young pregnant patient with aggressive regimen and we
      achieved full remission of the disease without affecting the fetus adversely. The
      management options are discussed thoroughly.

PMID- 18040903
TI  - [Diagnostic accuracy of the Phototest for cognitive impairment and dementia].
AB  - INTRODUCTION: The recently developed Phototest is a simple, easy and very brief
      (<3 minutes) test with theoretical advantages over available dementia screening
      tests. Our objective was to evaluate its diagnostic accuracy under routine
      clinical conditions. MATERIAL AND METHODS: A phase II cross-sectional validation
      study of diagnostic tests was performed in a sample of 308 patients referred to a
      general neurology department and in a group of 70 healthy individuals. The
      diagnostic accuracy (DA) of the Phototest was assessed and compared with that of
      the Eurotest and a verbal fluency test (VFT) in relation to the clinical
      diagnosis of dementia (DEM) and cognitive impairment (CI) by calculating the area
      under the ROC curve (aROC) and determining Sensitivity (Se), Specificity (Sp) and
      likelihood ratios. RESULTS: The total sample comprised 225 subjects without CI
      (NOR), 58 with CI and without DEM and 95 with DEM. Phototest results showed a
      normal distribution in NOR subjects (33.4 +/- 3.9 [mean +/- standard desviation])
      and were not influenced by educational variables. The DA of the Phototest for DEM
      and CI (0.95 +/- 0.01 [aRO C+/- Se]) was similar to that of the Eurotest and
      higher for both tests than that of the VFT. The cutoff points of 25/26 for DEM
      (Se=0.88 [0.80-0.94], Sp=0.90 [0.86- 0.93]) and 28/29 for CI (Se=0.90 [0.84
      0.94], Sp=0.90 [0.83-0.93]) maximised the sum of Se and Sp. CONCLUSIONS: The
      Phototest is a very short test of easy application that is applicable to
      illiterate subjects, uninfluenced by educational variables and useful to identify
      CI and DEM in routine clinical practice.

PMID- 18040904
TI  - [Arteriovenous malformations associated with Klippel-Trenaunay-Weber syndrome].

PMID- 18040905
TI  - [Progressive dysautonomia as initial manifestation of anti-Hu antibody-related
      syndrome].
AB  - INTRODUCTION: The anti-Hu antibody are associated with central nervous system
      paraneoplastic syndromes such as sensory neuropathy, cerebellar ataxia or limbic
      encephalitis. The isolated autonomic dysfunction as the presenting manifestation
      of anti-Hu antibody-related paraneoplastic syndrome is extremely infrequent. CASE
      REPORT: A 68 year-old male presented with a two-month history of severe
      constipation following of orthostatic hypotension, impotence, urinary retention
      and intestinal pseudo-obstruction as manifestations of progressive dysautonomia.
      Four months after the onset of these symptoms, he developed paresthesias in the
      hands and feet, motor weakness in both upper and lower limbs and ophtalmoplegia.
      Anti-Hu antibodies were positive in serum and cerebrospinal fluid, although tumor
      was not found. CONCLUSIONS: Progressive dysautonomia may result from a number of
      diseases. We encourage to consider also the possibility of anti-Hu antibody
      related syndrome, despite the case that it is a very unusual isolated initial
      manifestation.

PMID- 18040907
TI  - [Acute transverse myelitis after obstetric epidural anesthesia].
AB  - INTRODUCTION: Acute transverse myelitis is an acute or subacute disorder of the
      spinal cord resulting in motor, sensory and sphincter dysfunction secondary to
      various causes. CASE REPORT: We present a 32 year-old female patient with an
      acute episode of bladder dysfunction and fever, followed by motor and sensory
      dysfunction in legs with sensory spinal level at D2-D3, two weeks after an
      eutocic delivery with uncomplicated epidural anesthesia. The cerebrospinal fluid
      (CSF) showed mild lymphocytic pleocytosis, high protein levels with normal
      glucose concentration, absence of oligoclonal bands and negative serum and CSF
      virology screening. The cervicodorsal magnetic resonance imaging showed widening
      of the spinal cord with diffuse patchy hyperintensity on the C6-D1 and D2-D5
      levels without contrast enhancement. The patient was treated with intravenous
      high doses of methylprednisolone with favorable outcome and complete recovery
      within one year and no relapses two years after the episode. DISCUSSION: The main
      etiologies of non-compressive acute myelopathy as multiple sclerosis, systemic
      diseases, spinal cord infarct and direct infections have been ruled out with the
      complementary examinations. We consider that our patient had a parainfectious
      acute transverse myelitis and epidural anesthesia could be an incidental but
      possible contributing factor.

PMID- 18040906
TI  - [Adult-onset primary focal foot dystonia].
AB  - INTRODUCTION: Adult-onset primary focal foot dystonia is a rare event. Up to now,
      only 7 cases have been reported in the literature. Since the idiopathic-type food
      dystonia is uncommon in adults, secondary types must be ruled out. CLINICAL
      REPORT: We present the case of a 51 year woman with a 3 year history of focal
      food dystonia. She had abnormal posture of the foot with plantar flexion and
      inversion, which worsened with action. Complementary studies aimed at ruling out
      secondary causes were all negative. The dystonia remained limited to her food and
      she did not develop any other neurological symptoms. She benefited from botulinum
      toxin treatment. CONCLUSIONS: Primary focal foot dystonia is uncommon in adults.
      The most common pattern is plantar and five toes flexion. Associated pain is
      common. Its pathogenesis is only partially understood, the neurophysiologic
      studies and functional resonance showing a loss of inhibitory control at spine
      and brainstem levels, abnormal cortical plasticity and altered sensorimotor
      integration. The response of this disorder to drugs is poor, however, the
      patients may benefit from botulinum toxin infiltrations of the muscles involved.

PMID- 18040908
TI  - [Headache in patient with neurofibromatosis type 1].
AB  - INTRODUCTION: Neurofibromatosis type 1 (NF-1) is an autosomal dominant
      neurocutaneous syndrome due to a mutation in chromosome 17 (at 17q11.2). The
      association of NF-1 with Arnold-Chiari I malformation has been previously
      described. CASE REPORT: A 23 year-old woman diagnosed of NF-1 based on the
      presence of cutaneous lesions and a familiar background consistent with this was
      referred to the neurologist due to oppressive frontooccipital bilateral headache
      that irradiated to both shoulders. It worsened on physical effort and Valsalva
      maneuver and had more than one year of evolution. Physical examination showed
      multiple cafe au lait spots in the trunk and cutaneous neurofibromas in the
      cervico-dorsal region, as well as short height and mild dorsal scoliosis.
      Neurological examination showed hyperreflexia in both legs and slight light touch
      and pinprick hyposthesia in the left arm. The magnetic resonance findings
      suggested Arnold - Chiari I malformation with associated cervical syrinx, without
      any other abnormalities in the central nervous system. She underwent surgery,
      with partial improvement of the symptoms. CONCLUSION: The association between NF
      1 and Arnold- Chiari I malformation seems to be more than coincidental. The
      abnormalities of the embrionary development secondary to NF-1 would be
      responsible for the posterior fossa hypoplasia found in Arnold-Chiari
      malformation. Our case focuses on the idea that Arnold- Chiari malformation
      should be included in the list of abnormalities reported in NF-1.

PMID- 18040910
TI  - [Render unto Caesar the things which are Caesar's].

PMID- 18040909
TI  - [Use of levetiracetam in the management of post-anoxic myoclonias. A report of
      two cases].

PMID- 18040911
TI  - [Surgical treatment of Parkinson's disease: is it time to change the time of the
      indication?].

PMID- 18040912
TI  - [Optical coherence tomography, an inflection point in neuro-ophthalmology].

PMID- 18040913
TI  - [International Dry Eye Workshop (DEWS). Update of the disease].

PMID- 18040914
TI  - [Public health warnings of solar retinopathy risk in European newspapers prior to
      the 2006 solar eclipse].

PMID- 18040915
TI  - [Brown-McLean syndrome and refractive phakic anterior chamber intraocular
      lenses].

PMID- 18040916
TI  - [Photodynamic therapy in angioid streaks].
AB  - OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy in
      choroidal neovascularization associated with angioid streaks. METHODS: We
      performed a retrospective study of eleven eyes (eight patients) with subfoveal,
      juxtafoveal or extrafoveal neovascularization, which received at least one
      session of photodynamic therapy. Treatment efficacy was evaluated by visual
      acuity (VA) testing, color photography and fluorescein angiography. The mean
      follow-up was 13.2 months. RESULTS: Ten eyes presented subfoveal
      neovascularization, one eye presented juxtafoveal and another eye extrafoveal
      neovascularization. VA was unchanged in two patients, increased in one patient,
      and decreased in eight patients following photodynamic therapy. Nine eyes
      presented conversion to a fibrotic disciform lesion, whereas leakage persisted in
      two eyes after one session of photodynamic therapy. Recurrence of choroidal
      neovascularization appeared in three eyes. CONCLUSIONS: Photodynamic therapy in
      choroidal neovascularization related to angioid streaks does not appear to alter
      the course of this disease, but it does slow its progression.

PMID- 18040917
TI  - [Contact lens fitting in 133 eyes with irregular astigmatism].
AB  - PURPOSE: To study the adaptation of contact lens in a sample of 133 eyes with
      irregular astigmatism. METHODS: A retrospective study was made in 133 eyes with
      irregular astigmatism. The selection criterion was to obtain a sample population
      with irregular astigmatism that was unlikely to be corrected with spectacles or
      conventional contact lens. A complete ophthalmologic exploration which included a
      topography with the Eye-Sys 2000 corneal topographer was made was made. The
      variables analyzed in the study were: refraction, visual acuity before and after
      the correction, cause of the astigmatism and contact lens used. RESULTS: An equal
      number of women and men were enrolled in the study. The right eye was studied in
      52% of cases, and the left eye in 46%. Both eyes were affected in 67% of the
      subjects. The reason for the astigmatism was keratoconus in 110 eyes (78.2%), and
      there were 4 corneal injuries, 9 ocular infections, and 6 idiopathic
      astigmatisms. Among the contact lens used in the study: in 103 eyes a hybrid lens
      (Softperm) was adapted, in 20 eyes a piggy-back system, in 5 eyes a thick
      hydrophilic lens (Queratosoft), in 4 eyes a hydrophilic contact lens and in 3
      cases a rigid gas permeable contact lens. The average visual acuity before the
      adaptation was 0.28 (SD 0.24) (range 0.1-0.8). After the use of the lens the
      average visual acuity was 0.81 (SD 0.23) (range 0.1-1). Statistically significant
      differences between the visual acuity before and after treatment were found, with
      an improvement of 0.53 (SD 0.28) obtained. CONCLUSION: Only with experience using
      a large variety of non-conventional contact lens can a specialist contact lens
      ophthalmologist achieve a good result.

PMID- 18040918
TI  - [HLA-A24: risk factor in proliferante diabetic retinopathy].
AB  - OBJECTIVE: Proliferative diabetic retinopathy (PDR) is characterized by a
      progressive visual impairment in young people. Human leucocyte antigen (HLA)-A24
      is a well-established factor associated with the pancreatic islets of Langerhans
      lost in this process. Our aim was to study further the relationship of the HLA
      A24 associated with PDR. MATERIALS AND METHODS: We evaluated a group of patients
      with PDR (n=95) and a healthy control group (n= 60). HLA-A24 for each participant
      in the study was determined by molecular hybridization techniques. RESULTS: The
      control group showed a lower frequency of HLA-A24 compared with the PDR group (p
      = 0.043). HLA-A24 was associated with PDR (OR = 5.4; 95% CI= 3.2-7.6; p< 0.001).
      CONCLUSIONS: HLA-A24 is not a protective factor for PDR, but is a risk factor of
      its development.

PMID- 18040919
TI  - [Chronic ethanol feeding induces oxidative stress in the rat retina: treatment
      with the antioxidant ebselen].
AB  - PURPOSE: To assess the involvement of biochemical and functional changes to the
      retina after chronic ethanol intake in adult rats, and the capacity of the
      antioxidant ebselen to prevent these changes. METHODS: Male Sprague-Dawley rats
      were used in the study. They were fed an ethanol-containing liquid diet, whereas
      a control group was given an ethanol-free isocaloric diet. After six weeks of
      experiment, the eyes were extracted and homogenized without the lens, and markers
      of oxidative stress were assayed, i.e., glutathione (GSH) and malondialdehyde
      (MDA) as an intracellular antioxidant and a lipid peroxidation product,
      respectively. Moreover, retinal function was assessed by electroretinogram (ERG).
      RESULTS: The retinal MDA concentration was significantly increased in the ethanol
      fed animals compared to controls, whereas the GSH content was significantly
      reduced in the ethanol-fed group compared to controls. Ethanol also induced a
      decrease in ERG b-wave amplitude. Ebselen treatment restored the MDA and GSH
      concentrations and ERG b-wave amplitude to control values. CONCLUSION: These
      results indicate that chronic alcohol consumption alone and without the influence
      of nutritional factors alters the retinal redox status as well as its function
      (ERG). Further studies are required to better understand the protective mechanism
      of ebselen in this experimental model of chronic alcoholism.

PMID- 18040920
TI  - [Spontaneous bleeding to vitreous cavity during fluorescein angiography].
AB  - CASE REPORT: We report a case in which active bleeding from a posterior pole
      intraretinal microvascular anomaly (IRMA) occurred in a diabetic patient.
      DISCUSSION: Documentation of active bleeding during the performance of
      fluorescein angiography is extremely rare. We discuss the origin of the bleeding.

PMID- 18040921
TI  - [Dysthyroid ophthalmopathy associated with hypothyroidism].
AB  - CASE REPORT: Graves' ophthalmopathy (exophthalmos, muscular and eyelid
      infiltration) is associated almost systematically to hyperthyroidism. A female
      patient was diagnosed with subclinical hypothyroidism and treated with oral
      thyroxine. Months later she developed bilateral exophthalmos and was serum
      positive for thyrotropin receptor antibodies. Thyroxine treatment was suspended,
      and it was verified that her condition had developed into primary hypothyroidism.
      A diagnosis of Graves' disease with hypothyroidism was made. DISCUSSION: The
      diagnosis was based on the existence of ophthalmopathy and positive serum
      antibodies, both specific indicators of Graves' disease. The coexistence of
      hypothyroidism with Graves' disease is exceptional, but possible.

PMID- 18040922
TI  - [Sectorial conjunctival epitheliectomy and amniotic membrane transplantation for
      partial limbal stem cells deficiency].
AB  - CASE REPORT: A 74-year-old man developed a partial limbal stem cell deficiency
      secondary to a chemical injury in the left eye. He was treated with a sectorial
      conjunctival epitheliectomy and amniotic membrane transplantation. After 3 weeks
      there was an intact, smooth and stable corneal epithelium. DISCUSSION: This case
      report emphasizes that conjunctival epitheliectomy and amniotic membrane
      transplantation appears to be a safe and effective method of restoring a stable
      corneal epithelium for cases of partial limbal stem cell deficiency.

PMID- 18040923
TI  - [Autoimmune hepatitis in a patient with serpiginous choroiditis].
AB  - CASE REPORT: We report the case of a patient with serpiginous choroiditis who
      developed an autoimmune hepatitis. DISCUSSION: The etiology of serpiginous
      choroiditis remains uncertain. An immune-mediated mechanism has been reported.
      This case shows an association between serpiginous choroiditis and autoimmune
      processes.

PMID- 18040924
TI  - [Paraneoplastic optic neuritis in an unknown small cell lung carcinoma defined by
      CRMP-5-IgG].
AB  - CASE REPORT: The case of a 64-year-old patient with bilateral, progressive and
      painless diminution of visual acuity is presented. Ophthalmologic evaluation
      revealed optic neuritis and vitreous cells in both eyes, at different stages.
      Suspecting a paraneoplastic optic neuritis, the study of antibodies was
      requested. This showed positivity to the marker CRMP-5-IgG. After
      mediastinoscopy, a small cell lung carcinoma was diagnosed. DISCUSSION:
      Autoantibody CRMP-5-IgG defines a paraneoplastic entity of combined optic
      neuritis and vitreous inflammatory cells. The serological positivity avoids the
      vitreous biopsy and expedites the search for cancer. In our case, it allowed the
      diagnosis a previously unidentified tumor.

PMID- 18040925
TI  - [Leak of intravitreal triamcinolone to the anterior chamber].
AB  - CASE REPORT: A 78-year-old man with phakic eyes underwent photodynamic therapy
      followed by intravitreal injection of triamcinolone. During the injection a white
      solution was observed in the anterior chamber. Slit lamp examination revealed
      white opacities in the inferior anterior chamber angle and neither inflammatory
      activity nor corneal changes were noticed. DISCUSSION: Intravitreal triamcinolone
      has been used for treating macular edema and various retinal vascular and
      inflammatory diseases. We describe the passage of triamcinolone to the anterior
      chamber during the injection in a phakic eye as a very unusual adverse effect,
      observed probably as a result of a zonular defect.

PMID- 18040926
TI  - [Penetrating orbitocranial injury after trivial eyelid trauma: a case report].
AB  - CASE REPORT: We report a patient who, while in a drunken state, sustained a
      cerebral hemorrhage associated with an apparently trivial eyelid injury after an
      aggressive attack with a metallic object. DISCUSSION: Any apparently trivial
      eyelid injury may be associated with serious cerebral lesions. Making a correct
      diagnosis that distinguishes between that of drunkenness and an organic injury is
      essential, because failure to do so may result in both clinical and legal
      repercussions.

PMID- 18040927
TI  - [Saint Francis of Assisi and trachoma].

PMID- 18040928
TI  - [Ferdinand Ritter von Arlt (Obergraupen, 1812 - Vienna, 1887].

PMID- 18040929
TI  - [Recent advances in extrinsic allergic alveolitis].
AB  - Extrinsic allergic alveolitis (hypersensitivity pneumonitis), especially
      humidifier lung, has been more frequently diagnosed over the last decades,
      whereas farmer's lung has decreased over the same time period. Today two types of
      the chronic course of extrinsic allergic alveolitis can be distinguished. The
      recurrent chronic course with a good prognosis may be differentiated from the
      insidious course with a poor prognosis by means of different histological
      patterns (UIP, NSIP, BOOP pattern). The characteristic neutrophilic infiltration
      of the lung in the insidious course cannot be detected by bronchoalveolar lavage
      (BAL) methods. Furthermore, lymphocytosis in the BAL can be absent or present at
      a low level. The CD4/CD8 ratio is not always decreased and may be normal or even
      increased in these insidious cases with a poor prognosis. Granulomas in the lung
      tissue, however, point to a good prognosis. In the diagnostic work-up of machine
      operator's and humidifier lung, it is advisable not only to look for serum
      antibodies against bacteria and molds but also for rapid growing mycobacteria in
      a sample of machine or humidifier water. IgM and IgG rheumatoid factors occur
      frequently in allergic alveolitis, especially in humidifier lung. The patients,
      however, do not suffer from arthritis. The IgM rheumatoid factor may simulate IgM
      antibodies against numerous infectious agents (e. g., Bordetella pertussis or
      Mycoplasma pneumoniae). Taking this phenomenon into account may improve the
      current differential diagnosis of allergic alveolitis.

PMID- 18040930
TI  - [Comparison of pulmonary compliance and the work of breathing with pulmonary
      function parameters in men].
AB  - BACKGROUND: Dynamic and static pulmonary compliance as well as the work of
      breathing are essential parameters for describing respiratory mechanics. However,
      current reference values or correlations with other pulmonary function variables
      have been established only in studies with small numbers of participants.
      Therefore, the aim of the present study was to compare pulmonary compliance and
      the work of breathing with different pulmonary function parameters in a large
      number of men. METHODS: In 208 healthy men, aged 20 to 70 years, spirometry,
      bodyplethysmography and carbon monoxide transfer factor measurements were
      conducted. The esophageal pressure method was used to measure dynamic (C (dyn))
      and static (C (stat)) compliance. RESULTS: C (dyn) and C (stat) were
      significantly correlated with total lung capacity (TLC), vital capacity (VC),
      forced expiratory volume in the first second (FEV (1)) and carbon monoxide
      transfer factor (T (LCO)). C (dyn) decreased with increasing age, while C (stat)
      was correlated with height. The elastic and non-elastic work of breathing were
      significantly correlated with airway resistance, but not with aging. CONCLUSIONS:
      Lung volumes are important for the interpretation of pulmonary compliance and the
      work of breathing and therefore have to be considered in the assessment of
      respiratory mechanics. In contrast, the work of breathing is essentially
      influenced by the airway resistance. With increasing age there is only a small
      decrease in pulmonary compliance and the work of breathing.

PMID- 18040931
TI  - [Case report: bilateral block of the brachial plexus--approaches, dosage and
      effectiveness].
AB  - A young man squeezed both hands in a bending machine with the result of complex
      hand injuries. Because of a high risk for general anesthesia, operation as well
      as postoperative analgesia was performed under bilateral brachial plexus block
      with the axillary approach. We discuss the considerations concerning the possible
      approaches with bilateral anesthesia of the brachial plexus under consideration
      of side effects and effectiveness. The needed dosage of the local anesthetics
      will be discussed.

PMID- 18040932
TI  - [Transfusion-related acute lung injury (TRALI)].
AB  - According to data of international hemovigilance registries, transfusion-related
      acute lung injury (TRALI) has emerged as the leading cause of transfusion-related
      mortality. Errors in the transfusion process, leading to ABO incompatible
      transfusion, represent the second most frequent cause of transfusion-related
      mortality, while infection risks of transfusion declined significantly. The
      following article describes the clinical picture of TRALI, its pathogenesis,
      diagnostic criteria as well as therapy recommendations and discusses possible
      preventing measures.

PMID- 18040933
TI  - [Xenon--the ideal anaesthetic agent?].
AB  - The noble gas xenon, besides its anaesthetic and analgesic properties, shows many
      characteristics of an ideal anaesthetic agent. However, due to high production
      costs, its application is limited In daily clinical routine. Recent studies
      suggested not only outstanding haemodynamic stability and rapid emergence from
      anaesthesia, but also xenon's capacity to mediate protection against ischaemic
      damage in various organs and tissues. Since xenon is devoid of toxicity and
      relevant side effects, it could be beneficial at least in a subset of patients at
      high risk, and xenon therefore may become a reasonable alternative in this
      patient population.

PMID- 18040934
TI  - [Therapeutic options for patients with acute lung injury].
AB  - The treatment of acute lung injury is one of the most challenging tasks in
      intensive care medicine. Conventional therapeutic options cover lung protective
      mechanical ventilation with low tidal volumes and adequate PEEP, restrictive
      fluid management, prone positioning, and early recruitment maneuvers. These
      options should be used in parallel and should be accompanied by a suitable anti
      infective therapy. In cases of refractory hypoxemia, inhaled nitric oxide offers
      in most patients a successful rescue option. In specialized centers the
      application of ECMO remains as a final ultima ratio.

PMID- 18040935
TI  - [Everything is variable in a routine case].

PMID- 18040936
TI  - [Anesthesia in children with congenital heart disease].
AB  - Anesthesiologists involved in the care of children with congenital heart disease
      (CHD) have to understand the pathophysiology of each cardiac lesion and
      anticipate the impact of the planned procedure. Often the dimished margin of
      hemodynamic stability determines the guidelines of care. In children with CHD
      maintainance of the homeostasis during anesthesia for a wide variety of
      procedures is the anesthesiologist's challenge. Left-to-right shunting means a
      volume load to the left ventricle frequently combined with pulmonary
      hypertension. Right-to-left shunting leads to a central cyanosis.

PMID- 18040937
TI  - [Anaesthesia in paediatric cardiology].
AB  - Diagnostic and interventional paediatric cardiology has become an increasing
      field of activity for anaesthesiologist in recent times. Besides a close
      interdisciplinary cooperation, the exact knowledge of the pathophysiology of the
      congenital heart diseases is essential. Especially the spectrum of interventional
      paediatric cardiology has extended considerably. In addition to traditionally
      intervention such as atrial septal defect closure and embolization of a patent
      ductus arteriosus, today's indications are also valvuloplasty and angioplasty as
      well as ventricular septal defects.

PMID- 18040938
TI  - [Anesthesia for patients with congenital heart disease undergoing non-cardiac
      surgery].
AB  - An increasing number of children who have undergone corrective surgery for
      congenital heart disease (CHD) reach adulthood every year. These survivors defy
      commonly used classification schemes for adults undergoing non-cardiac surgery.
      Due to lack of data, the risk-benefit assessment for undergoing non-cardiac
      interventions must be individualized. An interdisciplinary team approach is the
      corner stone for the safe delivery of anesthesia to this patient population. This
      review is meant to equip the anesthesiologist with the necessary tools for the
      safe perioperative sailing of his patient suffering from CHD.

PMID- 18040939
TI  - [How to calculate the budget of an anaesthetic or intensive care department from
      revenues of g-DRGs].
AB  - In Germany the economical framework of the health system in general and the
      hospitals in particular has changed dramatically over the last years. The
      conversion of funding to DRGs has implicated a reduction of budgets. The
      apportioning of budgets by keys of officially calculating hospitals forces single
      departments and disciplines to choose financial goals of a hospital as their
      particular interest and not the financial goals of a department. The calculation
      of a budget for a department of anaesthesia and/or intensive care medicine is
      possible from fractions of all DRGs, that have been generated inside a hospital
      within a period of one year. However, this calculation comprises some problems,
      because anaesthesia and intensive care medicine are interdisciplinary
      disciplines, which cannot influence its achievements and its processes solely by
      its own, but are dependent on efficiency and quality of its partners. Internal
      cost allocation for improving processes seems not to be sensible in the system of
      DRGs as long as it is used not only as an instrument of controlling, but also as
      an instrument of benchmarking.

PMID- 18040940
TI  - [Subcutaneous Granuloma annulare].

PMID- 18040953
TI  - [The radiologic branch practice according to contract physician rights' change
      law -- now possible also in blocked planning areas].

PMID- 18040956
TI  - [Historical development of health reporting on the community level--an academic
      void].
AB  - In the literature health reporting is often placed within the context of new
      public health. By doing so, health reporting is viewed as a historically new
      development distinct from the "old" medical statistics. This point of view,
      however, only holds true with a view to the medical statistics of the German
      postwar period in the 20th century. There is also a forgotten health reporting
      enrooted in the so-called "medical topographies" with a history reaching back
      more than 200 years. Part of this latter tradition are the Bavarian medical
      district reports ("Physikatsberichte") from the 19th century. These reports
      depicted the way of life and state of health of a population in combination with
      a social medical analysis with a strong action orientation. The demise of these
      forms of health reports began with the advent of bacteriology.

PMID- 18040957
TI  - [Urban shrinkage and challenges for the public health-care service].
AB  - In the 21st century, urban development is facing new challenges caused by the
      simultaneous growing and shrinking of cities and urban regions. Whilst the
      development patterns and instruments of urban growth are well-known and widely
      accepted, the processes of shrinkage with its broad consequences, sphere of
      impact and speed need intensive investigation. In particular, urban restructuring
      including housing demolition brings about psychological stress situations for the
      affected inhabitants. Until the present time public services, including health
      care, are poorly prepared to cope with the new situation. To take account of
      these new challenges, the adaptation of tasks, instruments and targets is
      urgently needed. To be successful, a continuous cooperation and communication
      between municipal institutions and housing enterprises responsible for urban and
      housing development is indispensable. Furthermore, appropriately focussed
      scientific research results can support the creation of adequate strategies and
      instruments.

PMID- 18040958
TI  - [Age- and sex-specific mortality in the Ruhr region from 1994 to 2004].
AB  - OBJECTIVE: Results of an analysis of the mortality in the Ruhr region have shown
      increased mortality rates and a corresponding lower life expectancy, relative to
      the federal state of North Rhine Westphalia (NRW) as a whole. For the years 2002
      2004 the male life expectancy was 0.86 years below the NRW level, and for females
      0.56 years under the NRW level. The analysis of the age- and sex-specific
      mortality rates be-tween the years 1994 and 2004 has demonstrated in which age
      groups mortality increased in the Ruhr region. METHOD: The mortality rates for
      all 15 municipalities and counties of the Ruhr region have been analysed
      according to different areas: centre of population (Ballungskern), conurbation
      areas (Ballungsrandzone), Ruhr City (alias Ruhrgebiet/Ruhr-Region) and NRW
      without Ruhr City. Eleven average values and three-year mean values were
      calculated to reduce the range of the year-values. Per cent deviations of the NRW
      values demonstrate the size of the differences. RESULTS: Comparisons between the
      centres of population, conurbation areas with NRW without Ruhr City demonstrate
      an increased mortality especially in the male and female age groups of 40 to 54
      years. A comparison of the municipalities with the highest life expectancy level,
      Bonn, with that with the lowest life expectancy level, Gelsenkirchen, for the
      years 2002-2004 shows a difference in the life expectancy of 2.7 years for
      females and 4.3 years for males. The male and female mortality rates of the age
      groups 40-59 years in Gelsenkirchen exceed the comparable rates in Bonn by 30% on
      average. CONCLUSION: In spite of increasing life expectancy in the Ruhr region
      from 1994 to 2004 the age-specific mortality rates of the 35-54-year-old
      population are increased, especially in the centres of population. The problem
      area is the centres of population with a complicated socio-demographic situation
      and worse indicators of the health status.

PMID- 18040959
TI  - [Policy counselling through public health reporting?].
AB  - For about 20 years public health reporting has increasingly been developed as a
      resource in health policy counselling. Both with regard to its use as well as its
      further development it is important to reflect on the possibilities and limits of
      this resource. A basis for this is provided by theories, models and hypotheses
      derived from the discussion about scientific policy counselling. In early
      conceptual reflections on the organisation of health reporting a technocratic use
      was rejected. This is reflected by the ideas and views about the institutional
      embedding of health reporting activities. Against the background of diverging
      opinions about the political dimensions of health reporting activities,
      reflections were guided by the decisionistic and pragmatic model of the
      "scientification of politics". Public health reporting must provide the
      possibility for being used in a flexible way in order to add a pragmatistic
      component to its decisionistic and strategic uses. For action-oriented,
      pragmatistic and scientific policy counselling through the health reporting
      discipline it is important to link "information about politically relevant facts"
      with the "targeted processing of knowledge geared towards problems in the field
      of decision-making processes" (expertise).

PMID- 18040960
TI  - [Local health policies and health planning from the viewpoint of the decision
      makers of the local authorities].
AB  - In 1997 the new law about Public Health Service (OGDG) in Northrhine-Westfalia
      was put into operation. It included two new sets of compulsory tasks: local
      health reporting (GBE) and local health conferences (KGK). These new tasks are
      installed as planning and steering instruments aiming for a better health-care on
      the local level. The central object is the knowledge-based formation of local
      health policies. Thereby, local representatives concerned with health and social
      services should participate as well as administrators and politicians. Since the
      middle of the 1990 s both new tasks have been established by the public health
      department of the county of Heinsberg in Northrhine-Westfalia. The experience of
      this department over almost ten years is the background for the empirical
      research project that is described in this paper. The study investigates the
      vocational practices, the decision-making and the health-related attitudes of the
      relevant local administrative and political representatives. The impulse for the
      start of the study was given by the constant reluctance of political and
      administrative top managers to make use of these new planning instruments in
      agenda setting and decision making. 44 high-ranking staff members and politicians
      (mayors, party chairmen, heads of departments far beyond the health office) were
      personally interviewed. Although they are not part of the health administration
      they claim to be occupied with quite a few health-related tasks. The overlapping
      of their set of tasks with the local health policies is evident for the
      interviewed managers. How-ever, this does not cause them to use the two new
      planning instruments. In particular, they do not participate in the local health
      conferences. They rather prefer the traditional path of policy making (parties,
      committees, fractions) even if these paths are less efficient than the new ones.
      The health conference is much more used by health-service providers as a platform
      for setting priorities and organising their implementation effectively. So far,
      the inclusion of the other local representatives (administrative managers, etc.)
      although they are concerned with health issues has not been achieved. This is
      also true for local politicians who are responsible for health-care policies. The
      authors of the paper see it to be the task of the local public health department
      to convince all these players that the health conference is a productive tool and
      a useful platform for the discussion of the health problems in the county and the
      coordination of necessary actions to be taken. The most important focus point is
      seen in the intersection of health policies with other local policies.

PMID- 18040961
TI  - [Gerodontology--a challenge also for public health services].
AB  - The dental services of the public health service (OGD) should not confine
      themselves to dental screening in kindergartens and schools but also turn their
      attention to the advancement of oral health in the special risk groups of the
      senior citizens. Although government resources are limited, new capacities could
      be gained by restructuring. Is it really prudent, in a lifetime perspective, for
      the OGD to solely focus on the oral health of youths while oral neglect in long
      term care carries on unabated? A stronger support by the OGD of gerodontology
      should be instituted on its boards, publicised in health reports, and implemented
      in supervisory bodies for quality management of the long-term care facilities. An
      endorsement of the structures of long-term care insurance and training facilities
      would be desirable. The OGD could assist the fitter seniors through specific
      education to participate in dental prevention programmes and motivate physicians
      to inspect the oral cavity. Furthermore, recommendations regarding the
      structuring of geriatric dental care by the OGD would be helpful. The OGD is a
      vital partner to gerodontology. Therefore, further projects should be conducted
      in cooperation with dental organisations.

PMID- 18040962
TI  - [German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS)--what comes next?].
AB  - From May 2003 to May 2006 the Robert Koch Institute conducted the German Health
      Interview and Examination Survey for Children and Adolescents (KiGGS). This study
      included 17,641 boys and girls together with their parents from 167 study
      locations. The aim of this nationwide interview and examination survey was to
      collect, for the first time in Germany, comprehensive and nationwide data on the
      health status of children and adolescents. In this description it is compared,
      for the example of overweight and obesity, which of the target sets of the survey
      have already been achieved. It is discussed how the scientific results may
      influence decision-making of politicians and how the data can be used for the
      main aim of improving the health status of children and adolescents.

PMID- 18040963
TI  - [The Brandenburg social index: a tool for health and social reporting at regional
      and communal levels in the analysis of data of school beginners].
AB  - A social index derived from examinations of prospective first graders is used for
      health reporting in the Federal State of Brandenburg. The Brandenburg social
      index consists of data from the medical examinations, which contain social
      anamnesis questions. Based on parents' education and employment, the social index
      is computed for each child and finally each child is assigned to a group of
      lower, middle or higher socioeconomic status. The simply made social index is not
      only used for analysing health and social inequalities but also for analysing the
      social situation and trends of young families. Social index data for prospective
      first graders have ben collected since 1994. Thus, the social index is part of
      the social reporting in Brandenburg. The present article illustrates with
      examples how the index is used. Finally, it is mentioned that the Brandenburg
      government uses the social index to control finances in the language promotion
      for kindergarteners in day-care centres.

PMID- 18040964
TI  - [Adolescent self-evaluation of body weight and body mass index].
AB  - On the basis of a representative sample (N=546) of adolescents of the city of
      Stuttgart (class levels 8 and 9) this article explores the extent to which the
      self-evaluation of body weight deviates from the classification of weight
      recommended by the German Arbeitsgemeinschaft Adipositas im Kindes- und
      Jugendalter (AGA, Working Committee on Obesity in Children and Adolescents). The
      analysis revealed that 47.7% of the girls and 38.2% of the boys do not correspond
      with the body mass index-based classification recommended by the AGA. This is
      particularly related to adolescents who are underweight or have normal weight.
      Concerning the self-evaluation of body weight, great gender differences were
      exposed: boys are likely to underestimate their weight {OR=1.85 CI (95%): [1.06
      3.13]}, whereas girls tend to overestimate their body weight {OR=2.08 CI (95%):
      [1.38-3.14]}. The findings are displayed in the context of current national and
      international research results. In conclusion, the role of public health services
      in terms of promoting healthy body weight is discussed.

PMID- 18040965
TI  - [Observed in kindergarten--taken into consideration in medical check-up 8/9: a
      cooperative model for improved early recognition of psychological problems].
AB  - At the initiative of a regional working group, 140 day care centres in Kreis
      Recklinghausen participate in a cooperative project. It is intended to contribute
      to the early screening of psychological problems in preschool children. Day care
      nurses fill in a form serving to record behavioural indicators of psychological
      problems and give it to the parents. The parents can then decide to hand it to
      the pediatrician on the occasion of their child's medical check up no. 8 or 9.
      After having considered this information in the examination context, the doctor
      returns the form to the parents. The form proved to be useful and the procedure
      performed well. The project should be implemented in other regions, too.

PMID- 18040966
TI  - [A concept to improve vaccination coverage in Bavaria].
AB  - The aim of the Bavarian immunisation concept is the effective implementation of
      national vaccination recommendations taking into account known characteristics in
      Bavaria and social groups with limited access to vaccinations. Furthermore, it
      intends to coordinate the various players in the field of vaccine-prevention of
      disease. Key points of this concept are, among others, improvement of the
      available data, definition of vaccination aims, implementation of vaccination
      recall systems during the regular examination on entering primary and secondary
      school, coordination and enforcement of vaccination campaigns in schools as well
      as steps for the qualification and motivation of the physicians involved in
      vaccination. In addition, an independent committee for the coordination of
      professionals and institutions participating in vaccine prevention in Bavaria was
      created. This "Bayerische Landesarbeitsgemeinschaft Impfen (LAGI)", which was
      established at the end of 2006 includes representatives from medical associations
      and corporations, health insurance companies and public health agencies and is
      the key for the realisation and further development of this concept.

PMID- 18040967
TI  - [The suitability of orthodontical groups of indications (OGI) for preventive
      dental examinations of the public health service].
AB  - In the context of the dental preventive medical examinations of the public health
      service, the orthodontical data-gathering in children's day-care centre and
      schools, in contrast to the diagnoses of caries disease, was made was based so
      far on a non-uniform methodology. In order to provide in future, also in the
      orthodontical sector, data material that is usable for comparative national and
      local health reporting, a uniform methodology should form the basis for the data
      acquisition. The present study makes a contribution to this objective. A goal of
      the work was to test two different collection instruments for their suitability
      as objective tools in the context of the preventive dental medical examinations.
      The occurrence and the severity level of dentofacial anomalies as well as the
      orthodontic treatment status of Thuringian school children of defined age groups
      (9 to 11 years old, 12 to 13 years old) were recorded and the orthodontic
      treatment need was determined. In the younger age group valid the orthodontical
      groups of indications (OGI) were found for the first time in Germany; in the
      older group we tested the already long established Dental Aesthetic Index (DAI)
      and equipment application recommended by the World Health Organization (WHO). The
      work was a component of the task spectrum of the WHO Collaboration Centre
      "Prevention of Oral disease" of the Health Centre for Preventive Dentistry at the
      Centre for Tooth, Mouth and Jaw Dentistry of the Friedrich Schiller University of
      Jena in Thuringia. As investigation region, a rural area ("Landkreis Eichsfeld")
      of Thuringia was choosen. The study was arranged into a sociological and a
      clinical-epidemiological part. Altogether 1845 pupils were recruited from
      national schools. The questionnaire was based on the WHO-initiated "International
      Collaborative Study of Oral Health Outcomes" (ICS II study). The investigations
      took place in the context of the preventive medical examinations of the public
      health service. The results were based on the answers and findings of 691
      probants of the group of the 9-11 years old (AG 1) and 774 probants of the group
      of the 12-13 years old (AG 2). The sociological results of both age groups
      reflected social restrictions regarding the presence of dentofacial anomalies in
      an order of magnitude of 20% in the AG 1 and 7.3% in the AG 2. In the AG 1 11.4%
      confirmed an orthodontical treatment and 47.9% of the probants examined indicated
      a desire for treatment. On the other hand, the proportion of orthodontically
      treated in AG 2 amounted to 31.1% and 37.8% expressed a desire for treatment.
      Dentofacial anomalies determined with the help of the OGI in the AG 1 as the most
      frequent were in the form of a distal bite (sagittal stage/group of D) with 55.5%
      of the examined pupils being documented. However here severity development stages
      1 and 2 outweighed. Proportionally followed: confining (group E) with 21% and the
      vertical stage/deep bite (group T) with 7.8%. All other groups were represented
      by only small proportions, craniofacial anomalies (group A) were not diagnosed.
      Anomalies with severity development 1 and 2 were determined in 64.1% of the
      examined children. In the AG 2 examined with the DAI, the anomalies of space
      conditions with 58% exceeded anomalies of occlusion conditions with 38.9% and
      anomalies of dentition with 9.8%. An urgent orthodontical treatment need was
      determined in the AG 1 with 35.9% of the probants (severity development 3 to 5)
      and in the AG 2 with 16.8% (DAI values over 32). In the AG 2 too, over 60% DAI
      values from 13 to 25 were determined, 26% exhibited DAI values between 26 and 31.
      During the statistic evaluation the "Statistical Package found for Social
      Sciences (SPSS)" version 11.51 S with a significant level of 5% was used. Derived
      from the results of our analysis, the recommendation can be made that the
      methodology of the Orthodontical Groups of Indications for the employment is to
      be regarded as a possibility with dental preventive medical examinations in the
      public health service as a suitable equipment and so far allows the subjective
      estimate of the orthodontical treatment necessity to be made.

PMID- 18040968
TI  - Contributions to elevated metabolism during recovery: dissecting the excess
      postexercise oxygen consumption (EPOC) in the desert iguana (Dipsosaurus
      dorsalis).
AB  - The excess postexercise oxygen consumption (EPOC), a measure of recovery costs,
      is known to be large in ectothermic vertebrates such as the desert iguana
      (Dipsosaurus dorsalis), especially after vigorous activity. To analyze the cause
      of these large recovery costs in a terrestrial ectotherm, Dipsosaurus were run
      for 15 s at maximal-intensity (distance 35.0+/-1.9 m; 2.33+/-0.13 m s(-1)) while
      O(2) uptake was monitored via open-flow respirometry. Muscle metabolites
      (adenylates, phosphocreatine, and lactate) were measured at rest and after 0, 3,
      10, and 60 min of recovery. Cardiac and ventilatory activity during rest and
      recovery were measured, as were whole-body lactate and blood lactate, which were
      used to estimate total muscle activity. This vigorous activity was supported
      primarily by glycolysis (65%) and phosphocreatine hydrolysis (29%), with only a
      small contribution from aerobic metabolism (2.5%). Aerobic recovery lasted 43.8+/
      4.6 min, and EPOC measured 0.166+/-0.025 mL O(2) g(-1). This was a large
      proportion (98%) of the total suprabasal metabolic cost of the activity to the
      animal. The various contributions to EPOC after this short but vigorous activity
      were quantified, and a majority of EPOC was accounted for. The two primary causes
      of EPOC were phosphocreatine repletion (32%-50%) and lactate glycogenesis (30%
      47%). Four other components played smaller roles: ATP repletion (8%-13%),
      elevated ventilatory activity (2%), elevated cardiac activity (2%), and oxygen
      store resaturation (1%).

PMID- 18040969
TI  - Endogenous and environmental factors influence the dietary fractionation of 13C
      and 15N in hissing cockroaches Gromphadorhina portentosa.
AB  - Since DeNiro and Epstein's discovery that the (13)C and (15)N isotopic signatures
      of animals approximate those of their respective diets, the measurement of stable
      isotope signatures has become an important tool for ecologists studying the diets
      of wild animals. This study used Madagascar hissing cockroaches (Gromphadorhina
      portentosa) to examine several preexisting hypotheses about the relationship
      between the isotopic composition of an animal and its diet. Contrary to my
      predictions, the results revealed that the tissues of adult cockroaches raised
      for two generations on a diet of known isotopic composition did not demonstrate
      enrichment of heavy stable isotopes. Moreover, the (15)N signatures of
      cockroaches were neither influenced by periods of rapid growth (i.e., 300-fold
      increase in dry body mass over 120 d) nor by imposed periods of starvation
      lasting up to 80 d. The offspring born to mothers raised on known diets were
      enriched in (15)N. Diet-switching experiments showed that turnover times of (13)C
      were highly correlated with age and ranged from 9 to 10 d to 60 to 75 d in
      subadults and adults, respectively. Adults subjected to diet switches differed
      from the subadults in that the adults achieved equilibrated isotopic signatures
      that were shifted approximately 1.0 per thousand toward their respective original
      diets. Lipid fractions of adult cockroaches averaged 2.9 per thousand more
      depleted in (13)C than in lipid-free fractions, but no changes in (13)C were
      observed in aging adults. Exposure to reduced ambient temperature from 33 degrees
      C to 23 degrees C over 120 d did not influence isotopic signatures of tissues.
      Overall, the results of this study reveal that different endogenous and exogenous
      factors can influence the isotopic signatures of cockroaches. These findings
      reinforce the need to conduct controlled studies to further examine environmental
      factors that influence the relationships between the isotopic signatures of
      animals and their diets.

PMID- 18040970
TI  - Environmental correlates, plasticity, and repeatability of differences in
      performance among blacknose dace (Rhinichthys atratulus) populations across a
      gradient of urbanization.
AB  - Urbanization alters stream and watershed hydrology so that fish from urban stream
      systems are confronted with extreme flows during storms and runoff events. To
      test whether residence in urban streams is associated with altered swimming
      ability, we compared sprint and endurance swimming performances of eight
      populations of blacknose dace (Rhinichthys atratulus) from different watersheds
      along an urban/rural gradient. Watershed impervious surface cover, a measure of
      urbanization, was significantly correlated with sprint performance in dace from
      all stream types and endurance swimming performance (U(crit)) when only fish from
      urban streams were analyzed. Three estimators of water flow in a stream system,
      watershed area, mean annual discharge, and base-flow current speed, were all
      related to U(crit) in fish from nonurban streams. The U(crit) was significantly
      repeatable after 6 mo in the laboratory, but dace populations with exceptional
      U(crit) values lost ability under no-flow, "detraining" conditions. Sprint
      performance changed substantially in individual dace after 10 wk under no-flow
      conditions and was a significant function of the animal's original performance.
      Animals with high sprint performance tended to lose ability, whereas those with
      poor performance gained ability. Interpopulation differences in both sprint and
      endurance swimming were robust over multiple years of collection from the same
      sites.

PMID- 18040971
TI  - Water balance and arginine vasotocin in the cocooning frog Cyclorana platycephala
      (hylidae).
AB  - It is well established that forming a cocoon, for frog species capable of doing
      so, markedly reduces evaporative water loss; however, the capacity of cocooned
      frogs to maintain hydration during extended estivation is not well understood.
      The combined effects of long-term estivation and water loss were examined in the
      cocoon-forming species Cyclorana platycephala by assessing the hydration state of
      the frogs throughout a 15-mo estivation period. Frogs lost mass throughout the 15
      mo period to a maximum of 36%+/-6.5% of their initial standard mass. Plasma
      osmolality reached maximal levels by the ninth month of estivation at 487 mOsm
      kg(-1) and then remained stable to the fifteenth month of estivation. Urine
      osmolality continued to increase to the fifteenth month of estivation, at which
      point plasma and urine concentrations were isosmotic. The use of bladder water to
      counter losses from circulation was indicated by the relatively slow rate of
      increase in plasma osmolality with mass loss and the progressive increase in
      urine osmolality. For estivating frogs, evidence was found for a possible
      threshold relationship between plasma osmolality and plasma arginine vasotocin
      (AVT) concentration. After estivation, plasma AVT concentrations decreased
      markedly after 15-mo estivators were placed in water for 2 h, suggesting that
      high levels of AVT may not be integral to rapid rehydration in this species.

PMID- 18040972
TI  - Ingested energy differs between populations of the toad Bufo bankorensis from
      different altitudes.
AB  - We measured ingested energy (E(i)) and apparent digestibility efficiency (ADE) in
      two populations of Bufo bankorensis from different altitudes at three
      temperatures and during two seasons to test the hypothesis that the optimal
      temperature range (T(opt)) for E(i) and ADE has shifted to the lower range in
      highland toads and winter toads. The T(opt) for E(i) was 22 degrees C for the
      lowland and highland toads and did not vary between seasons, thus falsifying the
      hypothesis. ADE of the toads was 96%-99% at 15 degrees -30 degrees C, and there
      was no difference between populations or seasons. Furthermore, when fed with fast
      moving prey, the toads from both altitudes had similarly low E(i) at 15 degrees
      C; when fed with slow-moving prey, the highland toads increased E(i) at 15
      degrees C, but the lowland toads did not. These results suggest that the toads
      from different altitudes had different appetites, even though their feeding
      locomotion was hampered in both populations at low temperatures.

PMID- 18040973
TI  - Stress and demographic decline: a potential effect mediated by impairment of
      reproduction and immune function in cyclic vole populations.
AB  - The stress response is initially adaptive, operating to maintain homeostasis.
      However, chronic long-term exposure to stressors may have detrimental effects. We
      proposed that chronic stress may be a major factor in demographic vole cycles,
      inducing decline in high-density populations. We monitored four populations of
      the fossorial water vole Arvicola scherman, which undergo pluriannual demographic
      cycles in the Jura Mountains (France). Sampling was conducted during the high
      densities and the decline. We measured fecal corticosterone metabolites (FCMs) to
      assess stress levels and injected phytohemagglutinin to estimate the cell
      mediated immune response. We demonstrated that stress levels increase between the
      high densities and the decline in most of the vole populations. At the individual
      level, FCM concentrations varied with reproductive status and body condition.
      During the outbreak, we observed significantly higher levels of FCM
      concentrations in nulliparous females than in females that had previously
      reproduced. Moreover, a significant negative correlation was observed between
      concentrations of FCMs and both immunocompetence and body condition during
      population decline. These results might reflect an impairment of the female
      reproductive capability in high densities and accelerated senescence affecting
      immune function during decline, both arising from chronic stress.

PMID- 18040974
TI  - Behavioral and physiological significance of minimum resting metabolic rate in
      king penguins.
AB  - Because fasting king penguins (Aptenodytes patagonicus) need to conserve energy,
      it is possible that they exhibit particularly low metabolic rates during periods
      of rest. We investigated the behavioral and physiological aspects of periods of
      minimum metabolic rate in king penguins under different circumstances. Heart rate
      (f(H)) measurements were recorded to estimate rate of oxygen consumption during
      periods of rest. Furthermore, apparent respiratory sinus arrhythmia (RSA) was
      calculated from the f(H) data to determine probable breathing frequency in
      resting penguins. The most pertinent results were that minimum f(H) achieved
      (over 5 min) was higher during respirometry experiments in air than during
      periods ashore in the field; that minimum f(H) during respirometry experiments on
      water was similar to that while at sea; and that RSA was apparent in many of the
      f(H) traces during periods of minimum f(H) and provides accurate estimates of
      breathing rates of king penguins resting in specific situations in the field.
      Inferences made from the results include that king penguins do not have the
      capacity to reduce their metabolism to a particularly low level on land; that
      they can, however, achieve surprisingly low metabolic rates at sea while resting
      in cold water; and that during respirometry experiments king penguins are
      stressed to some degree, exhibiting an elevated metabolism even when resting.

PMID- 18040975
TI  - Phenotypic flexibility in cutaneous water loss and lipids of the stratum corneum
      in house sparrows (Passer domesticus) following acclimation to high and low
      humidity.
AB  - Resistance to water-vapor diffusion through the skin is thought to be conferred
      by lipids in the stratum corneum (SC), the outer layer of the epidermis. We
      tested the effect of ambient humidity on cutaneous water loss (CWL) and lipid
      composition of the SC by acclimating house sparrows (Passer domesticus) to either
      a dry (6.5 g/m(3) absolute humidity) or a humid (31 g/m(3)) environment for 3 wk
      at a thermoneutral temperature (30 degrees C). Sparrows in the dry-acclimated
      group reduced CWL by 36% compared with those in the humid environment. Relative
      to initial values, both groups of sparrows decreased CWL, 45% in the dry
      acclimated group and 23% in the humid group, suggesting that temperature is also
      an important stimulus for CWL apart from humidity. Both groups of acclimated
      sparrows decreased quantities of cholesterol, free fatty acids, and cerebrosides
      and increased the proportion of ceramides in their SC. Lipid amounts or
      proportions in the SC did not differ between dry- and humid-acclimated sparrows,
      but the free fatty acid : ceramide ratio was significantly lower in dry
      acclimated birds. Also, lipid composition was only correlated with CWL in dry
      acclimated sparrows, suggesting that structural changes to SC lipids are more
      tightly linked to CWL regulation in response to low humidity. Our results
      demonstrate phenotypic flexibility in CWL and lipid composition of the SC and
      provide support for a functional relationship between these traits.

PMID- 18040976
TI  - beta-Glucocerebrosidase activity in the stratum corneum of house sparrows
      following acclimation to high and low humidity.
AB  - Skin is an important avenue of water loss in terrestrial birds, so environmental
      conditions that necessitate water conservation should favor physiological
      mechanisms that reduce cutaneous water loss (CWL). Skin resistance to CWL is
      conferred by a barrier of lipid molecules located in the stratum corneum (SC),
      the outer layer of the epidermis. In mammals, SC barrier function depends on the
      conversion of cerebrosides to ceramides by the enzyme beta -glucocerebrosidase (
      beta -GlcCer'ase). Avian SC contains both cerebrosides and ceramides, suggesting
      that observed plasticity in CWL may be mediated by changes in beta -GlcCer'ase
      activity and resultant SC lipid composition. We tested the hypothesis that
      changes in ambient humidity would alter beta -GlcCer'ase activity by acclimating
      house sparrows (Passer domesticus) to either dry (6.5 g H(2)O m(-3) absolute
      humidity) or humid (31 g H(2)O m(-3)) conditions for 5 and 21 d at 30 degrees C
      and then measuring beta -GlcCer'ase activity from SC homogenates. Our results
      provide the first characterization of beta -GlcCer'ase activity in any
      nonmammalian vertebrate. Relative to nonacclimated controls, both dry- and humid
      acclimated sparrows had significantly elevated beta -GlcCer'ase activity at 21 d
      postacclimation. Across individuals, we observed negative correlations between
      beta -GlcCer'ase activity and both CWL and SC ceramide content. Although dry- and
      humid-acclimated sparrows did not differ in beta -GlcCer'ase activity, these
      results are consistent with our findings that both humidity treatments caused a
      reduction in CWL and similar changes in SC lipid composition. Our results
      demonstrate physiological plasticity in CWL and provide tentative support for a
      role of beta -GlcCer'ase in mediating this response.

PMID- 18040977
TI  - The rate of bone mineralization in birds is directly related to alkaline
      phosphatase activity.
AB  - Recent studies have suggested that a biochemical marker, plasma alkaline
      phosphatase (ALP), can be used as a general indicator of skeletal development in
      vertebrate animals. In birds, age-related variation in ALP activity, presumably
      due to bone formation processes, has been demonstrated, but to date, a direct
      connection between bone mineralization and enzyme activity has been elusive. In
      this study, we show that the activity of a bone isoform of ALP (bone ALP) is
      closely related to the overall rate of skeletal mineralization in nestlings of a
      small passerine bird, the great tit (Parus major L). Moreover, bone ALP activity
      predicted the rate of mineralization of leg and wing bones but not that of the
      skull. Liver isoform of ALP was only marginally related to the overall rate of
      skeletal mineralization, while no association with the mineralization of long
      bones was found. We conclude that bone ALP activity in the blood plasma is a
      reliable biomarker for skeletal mineralization in birds. This marker enables
      detection of subtle developmental differences between chicks of similar
      structural size, potentially facilitating the prediction of offspring mid- and
      long-term survival.

PMID- 18040978
TI  - Egg yolk carotenoids in relation to habitat and reproductive investment in the
      great tit Parus major.
AB  - Maternal allocation of antioxidants to egg yolk has been shown to affect early
      embryonic development and nestling survival. In environments with high levels of
      anthropogenic pollution, antioxidants (such as carotenoids) are important to
      protect the body from elevated oxidative stress. Thus, female allocation of
      antioxidants to yolk may be traded off against self-maintenance. Here we
      investigate maternal reproductive investment with respect to yolk carotenoid
      content and composition in relation to subsequent female condition and carotenoid
      status in urban and rural great tits Parus major. We found no differences between
      the urban and rural populations in total yolk carotenoids, egg mass, clutch size,
      hatching success, or female carotenoid status. Interestingly, however, rural eggs
      contained more zeaxanthin, a more potent antioxidant than lutein, which suggests
      that rural embryos have better antioxidant protection than urban embryos. Whether
      rural females actively transfer more zeaxanthin to the yolk or whether it
      passively reflects differences in dietary access or uptake needs to be further
      investigated. This highlights the importance of carotenoid identity and
      composition in future studies of carotenoid physiology, ecology, and signaling.

PMID- 18040979
TI  - Sucrose hydrolysis does not limit food intake by Pallas's long-tongued bats.
AB  - Nectarivorous bats include very dilute nectar in their natural diet, and recent
      work with Pallas's long-tongued bat Glossophaga soricina showed that sugar
      (energy) intake rate decreased at dilute sucrose solutions. However,
      chiropterophillous nectar is composed mainly of the hexoses glucose and fructose.
      Because bats fed hexose nectar would save the delay of hydrolyzing sucrose, we
      hypothesized that sugar intake rate should be higher on this diet than on sucrose
      nectar. We compared intake response in Pallas's long-tongued bats offered 1 : 1
      glucose-fructose (hexose) and sucrose diets at 5%, 10%, 20%, 30%, and 40%
      (mass/volume) sugar solutions. We also tested the hypothesis that sucrose
      hydrolysis limits food intake in bats. Intake response was the same in bats fed
      both types of diet: sugar intake rate was lower in dilute solutions and then
      increased with sugar concentration. Similar intake responses in both diets
      indicate that sucrose hydrolysis alone does not limit food intake and support the
      idea that the burden of processing excess water in dilute solutions plays a major
      role.

PMID- 18040981
TI  - A workflow to increase the detection rate of proteins from unsequenced organisms
      in high-throughput proteomics experiments.
AB  - We present and evaluate a strategy for the mass spectrometric identification of
      proteins from organisms for which no genome sequence information is available
      that incorporates cross-species information from sequenced organisms. The
      presented method combines spectrum quality scoring, de novo sequencing and error
      tolerant BLAST searches and is designed to decrease input data complexity.
      Spectral quality scoring reduces the number of investigated mass spectra without
      a loss of information. Stringent quality-based selection and the combination of
      different de novo sequencing methods substantially increase the catalog of
      significant peptide alignments. The de novo sequences passing a reliability
      filter are subsequently submitted to error tolerant BLAST searches and MS-BLAST
      hits are validated by a sampling technique. With the described workflow, we
      identified up to 20% more groups of homologous proteins in proteome analyses with
      organisms whose genome is not sequenced than by state-of-the-art database
      searches in an Arabidopsis thaliana database. We consider the novel data analysis
      workflow an excellent screening method to identify those proteins that evade
      detection in proteomics experiments as a result of database constraints.

PMID- 18040982
TI  - Marked correlations in protein expression identified by proteomic analysis of
      human spermatozoa.
AB  - The present work was started to explore whether a correlation could be detected
      among proteomic expression, protamine content and DNA integrity in human sperm
      cells. Towards this goal, we extracted the proteins present in the sperm cells
      from 47 sperm samples from infertile patients and from ten semen donors, analysed
      each sample by 2-D gel electrophoresis, and quantified the expression of 101
      spots identified by MALDI-TOF analysis. Additionally, the protamine content and
      DNA integrity were also determined. Several interesting proteins such as
      transcription factors, prohibitin, heat shock and proteasome proteins have been
      identified. We have found that the expression of an important number of proteins
      (58 different 2-D spots) is correlated in independent sperm samples at high
      statistical significance (p<0.001 and r>0.5). Additionally, eight proteins have
      also been found to correlate with DNA integrity and seven with protamine content
      (p<0.05). To our knowledge, this is the first report describing the correlation
      between proteomics, DNA integrity and protamine content. It also sheds new light
      into the fundamental aspects of the human sperm and points to new potential
      proteins involved in male infertility.

PMID- 18040983
TI  - Cytoplasmic proteome reference map for a glutamic acid-producing Corynebacterium
      glutamicum ATCC 14067.
AB  - We constructed a cytoplasmic proteome reference map for a glutamic acid producing
      Corynebacterium glutamicum ATCC 14067 by 2-DE and protein identification by MALDI
      TOF-MS and PMF using genome database of the type strain ATCC 13032. The map
      allowed us to identify 166 protein spots representing 139 different proteins. A
      considerable strain difference was observed in the proteomic images between
      strains ATCC 14067 and ATCC 13032 grown under the glutamic acid production
      conditions, suggesting the importance of strain-specific reference map for
      proteomic analysis.

PMID- 18040984
TI  - Multiple augmentation for interval-censored data with measurement error.
AB  - There has been substantial effort devoted to the analysis of censored failure
      time with covariates that are subject to measurement error. Previous studies have
      focused on right-censored survival data, but interval-censored survival data with
      covariate measurement error are yet to be investigated. Our study is partly
      motivated by analysis of the HIV clinical trial AIDS Clinical Trial Group (ACTG)
      175 data, where the occurrence time of AIDS is interval censored and the
      covariate CD4 count is subject to measurement error. We assume that the data are
      realized from a proportional hazards model. A multiple augmentation approach is
      proposed to convert interval-censored data to right-censored data, and the
      conditional score approach is then employed to account for measurement error. The
      proposed approach is easy to implement and can be readily extended to other
      semiparametric models. Extensive simulations show that the proposed approach has
      satisfactory finite-sample performance. The ACTG 175 data are then analyzed.

PMID- 18040985
TI  - Proteomics of the aqueous humor in healthy New Zealand rabbits.
AB  - There are several physiological roles postulated for aqueous humor, a liquid
      located in the anterior and posterior chamber of the eye, such as maintenance of
      the intraocular pressure, provision of nutrients, and removal of metabolic waste
      from neighboring tissues and provision of an immune response and protection
      during inflammation and infection. To link these function to specific or classes
      of proteins, identification of the aqueous humor proteome is essential. Aqueous
      humor obtained from healthy New Zealand white rabbits was analyzed using three
      synergistic protein separation methods: 1-D gel electrophoresis, 2-DE, and 1-DLC
      (RPLC) prior to protein identification by MS. As each of these separation methods
      separates intact proteins based on different physical properties (pIs, molecular
      weights, hydrophobicity, solubility, etc.) the proteome coverage is expanded.
      This was confirmed, since overlap between all three separation technologies was
      only about 8.2% with many proteins found uniquely by a single method. Although
      the most dominant protein presented in normal aqueous humor is albumin, by using
      this extensive separation/MS strategy, additional proteins were identified in
      total amount of 98 nonredundant proteins (plus an additional ten proteins for
      consideration). This expands the current protein identifications by approximately
      65%. The aqueous humor proteome comprises a specific selection of cellular and
      plasma based proteins and can almost exclusively be divided into four functional
      groups: cell-cell interactions/wound healing, proteases and protease inhibitors,
      antioxidant protection, and antibacterial/anti-inflammatory proteins.

PMID- 18040986
TI  - A twin study of the common vulnerability between heightened sensitivity to
      hypercapnia and panic disorder.
AB  - For unknown reasons the inhalation of CO(2)-enriched air mixtures evokes acute
      panic-like symptoms in people with panic disorder and in their unaffected
      relatives. This study was set to determine whether, and to what extent, CO(2)
      induced acute anxiety and panic disorder share the same genetic and environmental
      determinants. Cholesky structural equation models were used to decompose into
      genetic and environmental elements the correlation between self-assessed anxiety
      post-35%CO(2)-65%O(2) inhalation and interview-based DSM-IV lifetime diagnoses of
      panic disorder in 346 young adult twin pairs of the Norwegian Institute of Health
      Panel, 12% of whom had been invited to take part into the CO(2) study on the
      basis of self-reported symptoms of anxiety gathered 4-7 years before the
      provocation challenge. A full model corrected for the partially selective
      ascertainment showed that the phenotypic correlation between post-CO(2) anxiety
      and DSM-IV panic was largely due to additive genetic influences, while shared and
      unique environmental agents concurred to explain a relatively minor proportion of
      the correlation between these two traits. According to the best-fitting model the
      genetic correlation between post-CO(2) anxiety and panic was 0.81 (0.50-0.98); a
      common genetic factor was sufficient to explain the traits' covariation and a
      further, specific genetic factor was necessary to account for the residual
      phenotypic variance. The genetic determinants that lead to overreact to a
      hypercapnic stimulus coincide at a considerable extent with those that influence
      liability to naturally occurring panic. Environmental factors provide a modest-
      or no--contribution to the covariation of CO(2)-provoked anxiety with naturally
      occurring panic.

PMID- 18040987
TI  - High-throughput mutational screening for beta-thalassemia by single-nucleotide
      extension.
AB  - In this work a high-throughput method based on the single-nucleotide extension
      (SNE) reaction and multicolour detection in a DNA sequencer was developed to
      screen for eight mutations in the human beta-globin gene: IVSI.110, cd39, IVSI.1,
      IVSI.6, IVSII.745, HbC, HbS and cd6. The method has been validated on a large
      number of samples for the two most common mutations causing beta-thalassemia in
      the Mediterranean area (IVSI.110 and cd39). The development of a high-throughput,
      fast and reliable method to assay beta-thalassemia mutations represents a
      significant improvement in molecular diagnosis of this disease. The multicolour
      detection and the use of multiple injections further enhances the throughput of
      mutational screening by the DNA sequencer and facilitates automated genotyping
      for routine molecular diagnostics.

PMID- 18040988
TI  - Bifidobacterium carbohydrases-their role in breakdown and synthesis of
      (potential) prebiotics.
AB  - There is an increasing interest to positively influence the human intestinal
      microbiota through the diet by the use of prebiotics and/or probiotics. It is
      anticipated that this will balance the microbial composition in the
      gastrointestinal tract in favor of health promoting genera such as
      Bifidobacterium and Lactobacillus. Carbohydrates like non-digestible
      oligosaccharides are potential prebiotics. To understand how these bacteria can
      grow on these carbon sources, knowledge of the carbohydrate-modifying enzymes is
      needed. Little is known about the carbohydrate-modifying enzymes of
      bifidobacteria. The genome sequence of Bifidobacterium adolescentis and
      Bifidobacterium longum biotype longum has been completed and it was observed that
      for B. longum biotype longum more than 8% of the annotated genes were involved in
      carbohydrate metabolism. In addition more sequence data of individual
      carbohydrases from other Bifidobacterium spp. became available. Besides the
      degradation of (potential) prebiotics by bifidobacterial glycoside hydrolases, we
      will focus in this review on the possibilities to produce new classes of non
      digestible oligosaccharides by showing the presence and (transglycosylation)
      activity of the most important carbohydrate modifying enzymes in bifidobacteria.
      Approaches to use and improve carbohydrate-modifying enzymes in prebiotic design
      will be discussed.

PMID- 18040990
TI  - Recent advances in the application of capillary electromigration methods for food
      analysis.
AB  - This review covers the application of capillary electromigration methods to
      analyze foods and food components, including amino acids, biogenic amines,
      peptides, proteins, DNAs, carbohydrates, phenols, polyphenols, pigments, toxins,
      pesticides, vitamins, additives, small organic and inorganic ions, chiral
      compounds, and other compounds in foods, as well as those applications of CE for
      monitoring food interactions and food processing. The use of microchips as well
      as other foreseen trends in food analysis by CE are discussed. Papers that were
      published during the period June 2005-March 2007 are included following the
      previous review by Cifuentes (Electrophoresis 2006, 27, 283-303).

PMID- 18040989
TI  - Brominated flame retardants in US food.
AB  - We and others recently began studying brominated flame retardant levels in
      various matrices in the US including human milk and other food. This paper
      reviews the food studies. In our studies, ten to thirteen polybrominated diphenyl
      ether (PBDE) congeners were measured, usually including BDE 209. All US women's
      milk samples were contaminated with PBDEs from 6 to 419 ng/g, lipid, orders of
      magnitude higher than levels reported in European studies, and are the highest
      reported worldwide. We compared our market basket studies of meat, fish and dairy
      products with other US food studies of meat and fish. US studies showed somewhat
      higher levels of PBDEs than reported elsewhere. Fish were most highly
      contaminated (median 616 pg/g), then meat (median190 pg/g) and dairy products
      (median 32.2 pg/g). However, unlike some European countries where fish
      predominates, dietary intake of PBDEs in the US is mostly from meat, then fish
      and then dairy products. Broiling can decrease the amount of PBDEs per serving.
      We also measured levels of hexabromocyclododecane (HBCD), another brominated
      flame retardant, in human milk. The levels are lower than PBDEs, 0.16-1.2 ng/g,
      similar to European levels, unlike PBDEs where US levels are much higher than
      European levels.

PMID- 18040991
TI  - CE at the omics level: towards systems biology--an update.
AB  - This review provides an updated overview of recent developments and applications
      of CE based on previously published reports in the field of omic research. The
      increased number of published articles on omics shows that the field is growing
      and attracting the attention of many life science researchers. Due to
      developments in the omics sciences, many researchers have been studying systems
      biology, in which biological events in organisms are systematically interpreted
      through the combination of complex measurements from various methods resulting in
      high-throughput data. Given the challenges of such complex forms of analysis, CE
      is a strong candidate for generating omics data useful for acquiring the
      qualitative and quantitative knowledge necessary for systems-level investigation.
      By emphasizing CE for systems biology, this review will discuss and focus on the
      applicability of CE to systems-based analytical data at the genomic,
      transcriptomic, proteomic, and metabolomic levels from 2005 to the present.

PMID- 18040992
TI  - Advances in CE-mediated microanalysis: an update.
AB  - This review, as a continuation of two earlier reports, gives an overview of the
      recent developments, over the period from 2005 until now, in the use of
      electrophoretically mediated microanalysis (EMMA) methodology for the on-line
      study of enzymatic reaction and derivatization. The article is divided into two
      parts: (i) on-line enzymatic reaction by EMMA and (ii) on-line derivatization by
      EMMA. Following a brief introduction, a literature overview on enzymatic reaction
      is provided. The second part starts with an introduction of the purpose of
      derivatization and the nomenclature used in the area of in-capillary
      derivatization based on EMMA. The development of more integrated analytical
      platform that combines in-capillary derivatization and sample preconcentration is
      discussed. Reported derivatization procedures are summarized.

PMID- 18040993
TI  - Recent advances in the analysis of antibiotics by CE and CEC.
AB  - This article reviews the most recent developments concerning the determination of
      antibiotics by CE and CEC. The most employed CE separation modes were CZE and
      MEKC although microemulsion electrokinetic capillary chromatoghraphy was also
      employed. For the first time, CE was coupled to MS that was applied as a specific
      and confirmatory detection technique for the analysis of antibiotics. The
      analytical characteristics of the developed methodologies as well as the
      different applications reported in the literature on this subject from June 2005
      until May 2007 are included in this article. To give the most relevant
      information on this topic, the experimental conditions employed to achieve the
      analysis of antibiotics by CE and CEC are provided together with the main
      applications performed in the pharmaceutical, agrochemical, biological, food, and
      environmental fields, emphacizing sample preparation requirements needed in each
      case.

PMID- 18040994
TI  - Electrodriven methods for the enantioseparation of second-generation
      antidepressant drugs: an update.
AB  - Second-generation antidepressant drugs are increasingly prescribed world-wide by
      psychiatrists and primary care physicians. Generally speaking, they seem to be
      safer than traditional tricyclic antidepressant drugs, especially in overdose.
      However, most of them possess stereogenic centers, thus they can exist as
      enantiomeric couples. Since enantiomers can have even dramatically different
      pharmacokinetic and pharmacodynamic properties, the study of antidepressant
      chirality is of great importance. In fact, the application of enantioselective
      analytical techniques can be useful both for the quality control of
      enantiomerically pure formulations and for the pharmacovigilance and therapeutic
      monitoring of patients undergoing treatment with these drugs. The high efficiency
      and inexpensiveness of electrodriven methods makes them a very attractive
      alternative to the usual chromatographic methods. This review is an update (2004
      2007) of a previously published paper on recent electrodriven methods for the
      enantioseparation of second-generation antidepressants. In particular, the focus
      has been put on selective serotonin reuptake inhibitors such as citalopram and
      sertraline, noradrenergic and specific serotonergic antidepressants, such as
      mirtazapine and tetracyclic antidepressants such as mianserin, as well as on
      multianalyte methods.

PMID- 18040995
TI  - Determination of amino acids by micellar EKC: recent advances in method
      development and novel applications to different matrices.
AB  - The extensive use of CE for the analysis of amino acids has been well documented
      in a series of research articles and reviews. Aim of this report is to address
      the attention of the reader on the recent advances of micellar electrokinetic
      chromatography for the separation and determination of these analytes.
      Enhancements in selectivity of this technique through the use of pseudostationary
      phases containing mixed micelles, polymers, and chiral selectors are presented.
      Selected applications concerning separation and quantitation of even minute
      amounts of amino acids in: (i) biological fluids; (ii) microdialysates; (iii)
      plant cells; (iv) food stuff; and (v) pharmaceutical formulations have also been
      covered. Advantages of MEKC over other techniques for the amino acid analysis
      have been underlined.

PMID- 18040996
TI  - Treatment 'mismatch' in early prostate cancer: do treatment choices take patient
      quality of life into account?
AB  - BACKGROUND: Pretreatment urinary, bowel, and sexual dysfunction may increase the
      toxicity of prostate cancer treatments or preclude potential benefits. Using
      patient-reported baseline dysfunction from a prospective cohort study, we
      determined the proportion of patients receiving relatively contraindicated
      ('mismatched') treatments. METHODS: Baseline obstructive uropathy and bowel
      dysfunction relatively contraindicate brachytherapy (BT) and external beam
      radiation therapy (EBRT), respectively, because they increase patients'
      vulnerability to treatment-related toxicity. Baseline sexual dysfunction renders
      moot the intended benefit of nerve-sparing radical prostatectomy (NSRP), which is
      to preserve sexual function. We categorized patients' clinical circumstances by
      increasing complexity and counted the mismatches in each, expecting weaker or
      multiple contraindications to increase mismatched treatments. RESULTS: Of 438
      eligible patients, 389 (89%) reported preexisting dysfunction, and more than one
      third received mismatched treatments. Mismatches did not significantly increase
      with clinical complexity, and watchful waiting was very infrequent, even when all
      treatment options were contraindicated. Patient age and comorbidity, but not
      preexisting dysfunction, were associated with treatment choice. As expected,
      mismatched BT and EBRT led to worsened urinary and bowel symptoms, respectively,
      and NSRP did not improve outcomes after baseline sexual dysfunction. CONCLUSIONS:
      Pretreatment dysfunction does not appear to reliably influence treatment choices,
      and patients receiving mismatched treatments had worse outcomes. Further study is
      needed to determine why mismatched treatments were chosen, including the role of
      incomplete patient-physician communication of baseline dysfunction, and whether
      using a validated questionnaire before treatment decision-making would bypass
      this difficulty. Treatment mismatch may be a useful outcome indicator of the
      quality of patient-centered decisions.

PMID- 18040997
TI  - Racial differences in pain during 1 year among women with metastatic breast
      cancer: a hazards analysis of interval-censored data.
AB  - BACKGROUND: Longitudinal tumor-specific studies of cancer pain across the disease
      trajectory provide insight into the course of pain. Information on pain
      predictors refines our understanding of patients with greatest distress and need.
      METHODS: The authors studied 1124 women with metastatic breast cancer and bone
      metastases, all of whom received standard treatment in an international clinical
      trial conducted from October 1998 to January 2001. The Brief Pain Inventory (BPI)
      was administered repeatedly during the course of 1 year. Hazard models were
      fitted to identify baseline and time-dependent covariates as predictors of pain
      worsening within cumulative 80-day intervals during the year. RESULTS: Increased
      severe pain hazards were associated with non-Caucasian race (hazard ratio [HR] =
      2.52; 95% CI, 1.69-3.76), restricted performance status (HR = 1.73; 95% CI, 1.13
      2.64), and radiation therapy in a previous interval (HR = 2.86; 95% CI, 1.61
      5.09). Estimated cumulative rates for not yet reaching a BPI score of 7 or above
      ranged from 0.79 (0.72-0.85) in the first interval to 0.64 (0.55-0.74) in the
      last interval for non-Caucasian women, whereas these rates ranged from 0.91 (0.89
      0.93) to 0.84 (0.81-0.87) for Caucasian women. CONCLUSIONS: By using a time-to
      event hazards analysis for cancer symptom data, the authors demonstrated that non
      Caucasian race predicted poorer pain control among women with metastatic breast
      cancer. Disparity findings from cross-sectional studies were confirmed. Pain
      management strategies should take race into account as a risk factor for
      worsening pain outcomes, and further investigation should seek to uncover and
      resolve the reasons for this obvious disparity.

PMID- 18040998
TI  - Racial and ethnic differences in breast cancer survival: how much is explained by
      screening, tumor severity, biology, treatment, comorbidities, and demographics?
AB  - BACKGROUND: The reasons for race/ethnicity (R/E) differences in breast cancer
      survival have been difficult to disentangle. METHODS: Surveillance, Epidemiology,
      and End Results (SEER)-Medicare data were used to identify 41,020 women aged > or
      =68 years with incident breast cancer between 1994-1999 including African
      American (2479), Hispanic (1172), Asian/Pacific Island (1086), and white women
      (35,878). A Cox proportional hazards model assessed overall and stage-specific
      (0/I, II/III, and IV) R/E differences in breast cancer survival after adjusting
      for mammography screening, tumor characteristics at diagnosis, biologic markers,
      treatment, comorbidity, and demographics. RESULTS: African American women had
      worse survival than white women, although controlling for predictor variables
      reduced this difference among all stage breast cancer (hazards ratio [HR], 1.08;
      95% confidence interval [95% CI], 0.97-1.20). Adjustment for predictors reduced,
      but did not eliminate, disparities in the analysis limited to women diagnosed
      with stage II/III disease (HR, 1.30; 95% CI, 1.10-1.54). Screening mammography,
      tumor characteristics at diagnosis, biologic markers, and treatment each produced
      a similar reduction in HRs for women with stage II/III cancers. Asian and Pacific
      Island women had better survival than white women before and after accounting for
      all predictors (adjusted all stages HR, 0.61 [95% CI, 0.47-0.79]; adjusted stage
      II/III HR, 0.61 [95% CI, 0.47-0.79]). Hispanic women had better survival than
      white women in all and stage II/III analysis (all stage HR, 0.88; 95% CI, 0.75
      1.04) and stage II/III analysis (HR, 0.88; 95% CI, 0.75-1.04), although these
      findings did not reach statistical significance. There was no significant
      difference in survival by R/E noted among women diagnosed with stage IV disease.
      CONCLUSIONS: Predictor variables contribute to, but do not fully explain, R/E
      differences in breast cancer survival for elderly American women. Future analyses
      should further investigate the role of biology, demographics, and disparities in
      quality of care.

PMID- 18040999
TI  - Metastases to soft tissue: a review of 118 cases over a 30-year period.
AB  - BACKGROUND: Metastatic tumors presenting as soft tissue masses are relatively
      rare and can be the source of diagnostic confusion both clinically and
      pathologically. The authors' experience was reviewed at a large academic medical
      center over a 30-year period (1971-2000) with metastases to soft tissue. METHODS:
      The tumors in the study included mainly lesions involving skeletal muscle or
      skeletal muscle and subcutaneous tissue of the upper and lower limbs, trunk,
      shoulders, and buttocks. Direct extension from tumors originating in bone or
      adjacent organs, tumors involving the skin or areas known to contain abundant
      lymph nodes (ie, axilla, groin), and hematopoietic malignancies were excluded.
      RESULTS: One hundred and eighteen cases were identified; 60 patients were women
      and 58 were men. The age range was 20 to 87 years (median of 53.5 years). The
      primary tumor was located in the skin (19 patients), lung (13 patients), breast
      (13 patients), kidney (12 patients), colon and rectum (12 patients), uterus (8
      patients), ovary (5 patients), head and neck (tongue, pharynx, larynx, nasal
      cavity, and mandible) (5 patients), esophagus (2 patients), stomach (2 patients),
      cervix (2 patients), small bowel (2 patients), bone (2 patients), adrenal gland
      (1 patient), eye (1 patient), testis (1 patient), urinary bladder (1 patient),
      and salivary gland (1 patient). In 27% (32 of 118 cases) of cases, the soft
      tissue metastasis was the initial manifestation of the disease. In 13.5% (16 of
      118 cases) of cases the primary site of origin could not be identified. The sites
      of metastasis included the abdominal wall (25 patients), back, including scapular
      region (20 patients), thigh (17 patients), chest wall (15 patients), arm (15
      patients), shoulder (11 patients), buttock (5 patients), perineum (3 patients),
      leg (2 patients), foot (1 patient), umbilical area (1 patient), ankle (1
      patient), scalp (1 patient), and elbow (1 patient). The histologic classification
      of the tumors included carcinoma (83 patients), malignant melanoma (20 patients),
      sarcoma and carcinosarcoma (9 patients), malignant mixed Mullerian tumor (2
      patients), seminoma (1 patient), malignant teratoma (1 patient), malignant
      gastrointestinal stromal tumor (1 patient), and neuroblastoma (1 patient). Many
      of the tumors displayed histologic features that created difficulties for
      diagnosis and could be easily mistaken on routine histopathologic examination for
      a variety of primary soft-tissue sarcomas. Routine use of immunohistochemical
      stains aided in their proper recognition. CONCLUSIONS: Metastases are not an
      infrequent finding in soft tissue and they may represent the initial
      manifestation of the disease. Use of a basic panel of immunohistochemical stains
      is recommended for defining the cell type and arriving at the correct diagnosis.

PMID- 18041000
TI  - Immunity against the GBV-B hepatitis virus in tamarins can prevent productive
      infection following rechallenge and is long-lived.
AB  - GB virus-B (GBV-B) is the virus most closely related to hepatitis C virus (HCV).
      Thus, we have used GBV-B infection of tamarins, which develop acute hepatitis
      following experimental infection, as a surrogate model to study protective
      immunity. As challenge virus, we first produced a GBV-B pool from an infected
      tamarin, which was not infected with the related GBV-A viruses. Its infectivity
      titer was 10(6.6) tamarin 50% infectious doses per ml. Next, two tamarins that
      were convalescent from recombinant GBV-B infection were re-challenged. In the
      original infection viremia persisted for 8 and 12 weeks, respectively, and both
      animals developed moderately severe hepatitis. Each tamarin was re-challenged
      four times with 10(4.3) tamarin 50% infectious doses of the GBV-B challenge
      virus. In one animal, each re-challenge produced 1-2 weeks of viremia; hepatitis
      was observed following the first re-challenge. In the other animal, however, only
      the first re-challenge produced viremia, lasting 1 week. During the primary
      infection, peak GBV-B titers were about 10(8) genome equivalents/ml in both
      animals; following re-challenges, peak titers ranged from 10(3) to 10(6) genome
      equivalents/ml. Analysis of the polyprotein sequence of viruses recovered from
      both animals following the first re-challenge demonstrated that these did not
      represent immune escape variants since mutations were not detected.
      Neutralization studies suggested that the immunity was not humoral in nature. We
      also demonstrated that the immunity was long-lived: 1 year after the fourth
      challenge, the animal with sterilizing immunity had low titer viremia for only 1
      week following an additional challenge.

PMID- 18041001
TI  - Astrovirus detection in sporadic cases of diarrhea among hospitalized and non
      hospitalized children in Rio De Janeiro, Brazil, from 1998 to 2004.
AB  - We analyzed 379 stool samples collected from January 1998 through December 2004,
      from hospitalized and non-hospitalized children with diarrhea in Rio de Janeiro,
      Brazil. These samples had prior negative results for other enteric viruses and
      bacterial pathogens. The specimens were analyzed for HAstV detection by RT-PCR.
      HAstV genotypes were determined by sequence analysis of the RT-PCR products.
      Twenty (5.3%) out of 379 samples were positive for astrovirus. Astrovirus was
      equally common among inpatients and outpatients and among different age groups.
      Of 20 HAstV-infected children, 13 (65%) were either hospitalized or received
      medical care in the emergence department, which suggests that they had a more
      severe illness. Only 7 (35%) of the 20 HAstV-infected children attended walk-in
      clinics, which suggests that they had mild disease. Other then diarrhea, fever
      was the most common symptom among the HAstV-positive patients, followed by vomit
      and bloody diarrhea. HAstV-1 was the predominant strain although genotypes 2 and
      4 were also found. There was no obvious difference among HAstV strains detected
      from inpatients or outpatients or among different age groups. The study
      documented that astrovirus is an agent of acute diarrhea in children who are
      inpatients or outpatients in Rio de Janeiro, Brazil although it seems to be less
      common as a single cause of childhood diarrhea then rotavirus.

PMID- 18041002
TI  - Molecular epidemiology and genetic variability of respiratory syncytial virus
      (RSV) in Stockholm, 2002-2003.
AB  - The epidemiology and genetic variability of circulating respiratory syncytial
      virus (RSV) strains in Stockholm during the season 2002-2003 were studied in
      consecutive RSV isolates derived from respiratory samples and diagnosed in the
      laboratory. Two hundred thirty-four viruses were sequenced. The samples were
      mainly from children under 1 year old (79%). The phylogeny of the N-terminal part
      of the G gene was studied after amplification and sequencing. One hundred fifty
      two viruses belonged to subgroup B and 82 to subgroup A. The subgroup A viruses
      could be further divided into genotypes GA2 (25) and GA5 (57) and the subgroup B
      viruses into GB3 (137) and SAB1 (15) strains. These strains clustered with
      subgroup A and subgroup B strains from Kenya from the same period, as well as
      with strains from Great Britain from 1995 to 1998. The dominance of subgroup B
      strains in Stockholm during 2002-2003 is in agreement with findings from other
      parts of the world during the same years. Only two genotypes of subgroup A, GA2
      and GA5, were circulating during this time, and GA2 has been circulating in
      Sweden for more than 20 years. Consecutive strains from the same individual
      displayed no variability in the sequenced region, which was also true of strains
      that had been passaged in cell cultures.

PMID- 18041003
TI  - Detection of unusual rotavirus genotypes G8P[8] and G12P[6] in South Korea.
AB  - Five hundred four fecal specimens, collected between 2004 and 2006 from young
      children with acute diarrhea, were screened for rotavirus by ELISA with VP6
      specific antibody. Of these samples, 394 (78.2%) were confirmed as group A
      rotavirus and they underwent G- and P typing using a combination of ELISA, RT
      PCR, and sequence analysis methods. The dominant circulating G serotype was G1
      (35.6%) followed by G3 (26.4%), G4 (14.7%), and G2 (11.9%). There was a low
      prevalence of G9 (1.0%) and of unusual G type rotavirus, in particular, G12
      (0.5%) and G8 (0.3%). Of the P genotype rotavirus in circulation, P[8] (53.0%)
      was most common followed by P[6] (15.5%), P[4] (15.2%), and P[9] (2.3%).
      Determination of G- and P type combinations revealed that G1P[8] strains were
      most prevalent (25.4%), amid G3P[8] (16.8%), G2P[4] (6.3%), and G4P[6] (6.1%)
      strains. Unusual or rare combinations such as G2P[6], G2P[8], G3P[4], G2P[9],
      G1P[9], G3P[9], G12P[6], G1P[4], G3P[6], and G8P[8] were also found. Owing to the
      recent emergence of G8 and G12 rotavirus, the findings from this study are
      important since they provide new information concerning the local and global
      spread of rotavirus genotypes.

PMID- 18041004
TI  - Cellular chromosome DNA interferes with fluorescence quantitative real-time PCR
      detection of HBV DNA in culture medium.
AB  - Fluorescence quantitative real-time PCR (FQ-PCR) is a recently developed
      technique increasingly used for clinical diagnosis by detection of hepatitis B
      virus (HBV) DNA in serum. FQ-PCR is also used in scientific research for
      detection of HBV DNA in cell culture. Understanding potential FQ-PCR interference
      factors can improve the accuracy of HBV DNA quantification in cell culture
      medium. HBV positive serum was diluted with culture medium to produce three test
      groups with HBV DNA levels of 5 x 10(7) copies/ml (high), 5 x 10(5) copies/ml
      (medium), and 5 x 10(3) copies/ml (low). Chromosome DNA was extracted from HepG2
      cells and then added to high, medium, and low group samples at final
      concentrations of 0, 12.5, 25, 50, and 100 microg/ml. The samples were quantified
      by FQ-PCR and data were evaluated using statistical software. No marked changes
      were seen in the quantitative curves for high level HBV DNA samples when the
      samples were supplemented with 0-100 microg/ml of chromosome DNA. Interference
      was observed in medium level samples when 50 and 100 microg/ml of chromosome DNA
      was added. Interference was also observed in low level HBV DNA samples when the
      concentration of added chromosome DNA was greater than 25 microg/ml. The
      interference was eliminated when samples were digested by DNase I prior to PCR
      detection. In Conclusions, the presence of cellular chromosome DNA can interfere
      with the detection of HBV DNA by FQ-PCR. Removal of cellular chromosome DNA from
      culture media prior to FQ-PCR is necessary for reliable HBV DNA quantitative
      detection.

PMID- 18041005
TI  - Prevalence of hepatitis B and C serological markers among first-time blood donors
      in Brazil: a multi-center serosurvey.
AB  - Little data are available on the seroprevalence of, and risk factors for
      hepatitis B and C viruses (HBV and HCV) infection in Latin American countries. A
      multi-center serosurvey was conducted among 3,598 first-time blood donors (65%
      men) from Sao Paulo, Salvador and Manaus in Brazil. The gender-specific
      seroprevalences of antibodies against hepatitis B core antigen (anti-HBc) and of
      the hepatitis B surface antigen (HBsAg) in anti-HBc-positive sera were measured,
      and risk factors analyzed by gender. The gender-specific seroprevalences of
      antibodies against HCV (anti-HCV) were measured, but risk factors for HCV were
      not determined. Anti-HBc and HBsAg seroprevalences were not significantly
      different in men [101/2,341 (4.31%) and 4/2,229 (0.18%), respectively] and women
      [65/1,237 (5.25%) and 8/1,169 (0.68%), respectively], whereas the seroprevalence
      of anti-HCV was higher in women (12/1,238 [0.97%] vs. 9/2,353 [0.38%]; odds ratio
      [OR] = 2.49; 95% confidence interval [CI]: 1.0-6.0). No significant difference
      for HBV infection was found across the three study sites or by ethnic group. The
      seroprevalence of anti-HBc increased with age, but decreased with education level
      in both genders. Lifetime number of sexual partners was associated with anti-HBc
      prevalence among men (OR = 1.95; 95% CI: 1.2-3.1), but not women. The
      seroprevalence of HBV and HCV was low among Brazilian blood donors, and exposure
      increased with age in both genders.

PMID- 18041006
TI  - Association of TGF-beta1 codon 25 (G915C) polymorphism with hepatitis C virus
      infection.
AB  - Cytokines play a key role in the regulation of immune responses. In hepatitis C
      virus infection (HCV), the production of abnormal cytokine levels appears to
      contribute to the progression of the disease, viral persistence, and affects
      response to therapy. Cytokine genes are polymorphic at specific sites, and
      certain polymorphisms located within coding/regulatory regions have been shown to
      affect the overall expression and secretion of cytokines. The aim of the present
      study was to identify potential markers of cytokines genes associated with the
      susceptibility to HCV infection. The cohort was composed of 128 individuals
      infected by HCV and 94 healthy controls. Genotyping was carried out by PCR-SSP.
      The distributions of the following polymorphisms were compared in these groups:
      TNF-alpha (-308G/A [rs1800629]), TGF-beta1 (codon 10 T/C [rs1982073], codon 25
      G/C [rs1800471]), IL-10 (-1082 A/G [rs 1800896]; -819T/C [rs1800871]; -592A/C [rs
      1800872]), IL-6 (-174G/C [rs1800795]), and IFN-gamma (+874T/A [rs2430561]). This
      study demonstrated a statistically significant difference in the frequency of TGF
      beta1 codon 25 polymorphism between healthy subjects and those infected with HCV.
      No associations were observed between polymorphisms of TNF-alpha, IFN-gamma, IL
      10, TGF-beta1 codon 10, and IL-6 and HCV infection. These findings suggest that
      TGF-beta1 codon 25 polymorphism could be a host genetic factor associated with
      susceptibility to HCV infection.

PMID- 18041007
TI  - Critical behavior of KDCO3 from 2H and 39K single crystal NMR.
AB  - Potassium hydrogenocarbonate KDCO3 presents an order/disorder phase transition at
      Tc approximately 353 K. The critical behavior of this phase transition was
      studied by single crystal 2H and 39K NMR. The evolution of the order parameter as
      a function of temperature is quantified, and the critical exponent was
      determined, indicating a transition close to a tricritical point. The 2H Zeeman
      relaxation rate is strongly increased near the transition temperature. By
      calculating the noncritical contribution to the Zeeman relaxation rate, we show
      that the observed relaxation rate clearly presents a pseudo-divergent behavior
      near Tc, with a logarithmic singularity. The nature of the phase transition is
      discussed in the light of these results.

PMID- 18041008
TI  - Tryptamine derived amides with thiazole ring system from Thermoactinomyces strain
      TA66-2.
AB  - A moderately thermophilic actinomycete strain, which was identified as
      Thermoactinomyces strain TA66-2, was isolated from hot-spring water.
      Fermentation, followed by solvent partition and chromatographic separations,
      resulted in the isolation of two new and two known molecules. The structures of
      the new compounds were elucidated as 2-(1-Propionylaminoethyl)thiazole-4
      carboxylic acid [2-(1H-indol-3-yl)ethyl]amide and 2-(1-Acetylaminoethyl)thiazole
      4-carboxylic acid [2-(1H-indol-3-yl)-ethyl]amide by using spectral methods (1D-,
      2D-NMR and LC-ESI-MS).

PMID- 18041009
TI  - Secondary metabolites from Paronychia argentea.
AB  - Two new oleanane saponins (1 and 2) and one new flavonol glycoside (3) together
      with six known flavonoids, were isolated from the aerial parts of Paronychia
      argentea. Their structures were elucidated by 1D and 2D NMR experiments including
      1D-TOCSY, DQF-COSY, NOESY, HSQC, and HMBC spectroscopy, as well as ESI-MS
      analysis.

PMID- 18041010
TI  - 1H and 13C NMR spectra of C-6 and C-9 substituted 3-azabicyclco[3.3.1]nonanes.
AB  - The 1H and 13C NMR data for 3-azabicyclo[3.3.1]nonanes with OH and OMe
      substituents at C-6 and C-9 were measured using 1D (DEPT) and 2D (COSY, HSQC,
      HMBC, NOESY) experiments. Comparison of this NMR data illustrates the effects of
      stereochemistry and substitution at these positions.

PMID- 18041011
TI  - Unambiguous structural elucidation of base-modified purine nucleosides using NMR.
AB  - A general and unambiguous approach has been developed for structural elucidation
      of modified purine nucleosides using NMR spectroscopy. Systematic assignment of
      proton and carbon signals of modified nucleosides was firmly established by COSY
      and the anomerism of the glycosidic linkage of synthetic nucleosides clearly
      elucidated by NOESY experiments. Characteristic properties of 15N-isotopic
      labelling at specific positions of nucleosides were also employed for structural
      studies. The reported approach is applicable to other modified nucleosides and
      nucleotides, as well as nucleobases.

PMID- 18041012
TI  - Improved isotope ratio measurement performance in liquid chromatography/isotope
      ratio mass spectrometry by removing excess oxygen.
AB  - A low dead volume oxygen scrubbing system was introduced in a commercially
      available liquid chromatography/isotope ratio mass spectrometry (LC/IRMS)
      interface to enhance the analytical capability of the system. In the LC/IRMS
      interface carbon from organic samples is converted into CO(2) inside the mobile
      phase by wet chemical oxidation using peroxodisulfate (Na(2)S(2)O(8)). After
      passing the hot reaction zone, surplus oxygen (O(2)) remains dissolved in the
      liquid phase. Both CO(2) and O(2) diffuse through a transfer membrane into the
      helium carrier and are transferred to the mass spectrometer. The presence of O(2)
      in the ion source may have detrimental effects on measurement accuracy and
      precision as well as on filament lifetime. As a remedy, a new on-line O(2)
      removing device has been incorporated into the system. The new O(2) scrubber
      consists of two parallel hot copper reduction reactors (0.8 mm i.d., active
      length 120 mm) and a switch-over valve between them. One reactor is regenerated
      using He/H(2) while the other is actively scavenging O(2) from the gas stream.
      The capacity of each reduction reactor, expressed as usage time, is between 40
      and 50 min. This is sufficient for a single LC run for sugars and organic acids.
      A further increase of the reduction capacity is accompanied by a peak broadening
      of about 100%. After switching to a freshly reduced reactor the oxygen background
      and the delta(13)C values of the reference gas need up to 500 s to stabilize. For
      repeated injections the delta(13)C values of sucrose remain constant (+/-0.1 per
      thousand) for about 3000 s. The long-term stability for measurements of sucrose
      was 0.11 per thousand without the reduction oven and improved slightly to 0.08
      per thousand with the reduction oven. The filament lifetime improved by more than
      600%, thereby improving the long-term system stability and analytical efficiency.
      In addition the costs per analysis were reduced considerably.

PMID- 18041013
TI  - Recognition properties of donor- and acceptor-modified biphenyl-DNA.
AB  - The recognition properties of DNA duplexes containing single or triple
      incorporations of eight different donor-modified (OMe, NH(2)) and acceptor
      modified (NO(2)) biphenyl residues as base replacements in opposite positions
      were probed by UV-melting and by CD and fluorescence spectroscopy. We found a
      remarkable dependence of duplex stability on the natures of the substituents
      (donor vs. acceptor). The stabilities of duplexes with one biphenyl pair increase
      in the order donor/donor < acceptor/donor < acceptor/acceptor substitution. The
      most stable biphenyl pairs stabilize duplexes by up to 6 degrees C in T(m). In
      duplexes with three consecutive biphenyl pairs the stability increases in the
      inverse order (acceptor/acceptor < donor/acceptor < donor/donor) with increases
      in T(m), relative to an unmodified duplex, of up to 10 degrees C. A thermodynamic
      analysis, combined with theoretical calculations of the physical properties of
      the biphenyl substituents, suggests that in duplexes with single biphenyl pairs
      the affinity is dominated by electrostatic forces between the biphenyl/nearest
      neighbor natural base pairs, whereas in the triple-modified duplexes the increase
      in thermal stability is predominantly determined by hydrophobic interactions of
      the biphenyl residues with each other. Oligonucleotides containing amino biphenyl
      residues are fluorescent. Their fluorescence is largely quenched when they are
      paired with themselves or with nitrobiphenyl-containing duplex partners.

PMID- 18041014
TI  - Self-assembly of N2-modified guanosine derivatives: formation of discrete G
      octamers.
AB  - In the presence of Na(+) ions, two N(2)-modified guanosine derivatives, N(2)-(4-n
      butylphenyl)-2',3',5'-O-triacetylguanosine (G1) and N(2)-(4-pyrenylphenyl)
      2',3',5'-O-triacetylguanosine (G2), are found to self-associate into discrete
      octamers that contain two G-quartets and a central ion. In each octamer, all
      eight guanosine molecules are in a syn conformation and the two G-quartets are
      stacked in a tail-to-tail fashion. On the basis of NMR spectroscopic evidence, we
      hypothesize that the pi-pi-stacking interaction between the N(2)-side arms
      (phenyl in G1 and pyrenyl in G2) can considerably stabilize the octamer
      structure. For G1, we have used NMR spectroscopic saturation-transfer experiments
      to monitor the kinetic ligand exchange process between monomers and octamers in
      CD(3)CN. The results show that the activation energy (E(a)) of the ligand
      exchange process is 31 +/-5 kJ mol(-1). An Eyring analysis of the saturation
      transfer data yields the enthalpy and entropy of activation for the transition
      state: DeltaH(not =)=29 +/-5 kJ mol(-1) and DeltaS(not =)=-151 +/-10 J mol(-1) K(
      1). These results are consistent with an associative mechanism for ligand
      exchange.

PMID- 18041015
TI  - Selective detection of 5-methylcytosine sites in DNA.

PMID- 18041016
TI  - Layered silicates by swelling of AMH-3 and nanocomposite membranes.

PMID- 18041017
TI  - Determination of solvent-trapped products obtained by photolysis of aryl azides
      in 2,2,2-trifluoroethanol.
AB  - A series of nonfluorinated and fluorinated aryl azides with varied functionality
      patterns were irradiated in 2,2,2-trifluoroethanol with either a high-pressure or
      a low-pressure mercury lamp. Interestingly, one of the major products in these
      reactions was the result of the recombination of anilino and alkyl radicals to
      form the corresponding hemiaminal compounds. The structure of the recombination
      products was assigned unambiguously after proton/deuterium exchange experiments
      followed by MS and MS/MS analysis.

PMID- 18041018
TI  - Serological response to hepatitis E virus genotype 3 infection: IgG quantitation,
      avidity, and IgM response.
AB  - Sequential sera were collected from 18 acute cases of UK-acquired hepatitis E.
      The virus strains in all cases were of genotype 3. The IgM and IgG response to
      acute infection were documented over time using EIA kits based on a peptide
      antigen, pE2, which is derived from a genotype 1 strain of hepatitis E virus
      (HEV). Ninety-five percentage of acute sera were IgM positive; after 6 months or
      more only 12% remained positive. The kit was adapted to quantify the IgG response
      (in WHO U/ml) and to determine antibody avidity. Following acute infection, anti
      HEV IgG concentrations rose between 6.9- and 90-fold. IgG avidity was low (<25%)
      in most acute sera. After 6 months IgG avidity was greater than 50% in all cases.
      One patient with a poor IgM response and high avidity antibody in acute sera may
      have had a second HEV infection. Taken together, these results confirm that the
      pE2-based EIA kits are suitable for diagnosing acute HEV genotype 3 infection.
      With simple modifications the IgG kit can measure anti-HEV concentration and
      avidity, which can be used to confirm acute infection.

PMID- 18041019
TI  - Monocytes, but not T or B cells, are the principal target cells for dengue virus
      (DV) infection among human peripheral blood mononuclear cells.
AB  - A better understanding of the pathogenesis of dengue hemorrhagic fever and dengue
      shock syndrome requires the precise identification of dengue virus (DV)
      permissive target cells. To examine the relative DV permissiveness among cell
      subsets, we inoculated unfractionated human peripheral blood mononuclear cells
      with DV2-16681 in the presence or absence of pooled DV-immune human sera (PHS),
      and assessed infection with fluorescent dye labeled DV-specific monoclonal
      antibody and cell surface markers using flow cytometry. We found significantly
      higher levels of DV antigen staining on DV-infected than mock-infected primary
      monocytes (3.54 +/- 3.42% vs. 0.50 +/- 0.38%; P = 0.001). The magnitude of
      infection was markedly enhanced in the presence of highly diluted PHS (10.04 +/-
      6.10% vs. 3.54 +/- 3.42%; P = 0.015). Under identical experimental conditions,
      primary T or B cells were not infected either with or without the addition of PHS
      (0.06 +/- 0.04% and 0.44 +/- 0.22% for T and B cells, respectively). Furthermore,
      depletion of CD14+ monocytes prior to DV inoculation abrogated the detection of
      infected cells, and the addition of monoclonal antibodies to either FcgammaRI
      (CD64) or FcgammaRII (CD32) led to a 50-70% reduction in antibody-dependent
      enhancement (ADE) of DV infection. Collectively, these results provide further
      support to the notion that primary monocytes and FcgammaRs expressed on these
      cells may be important in the initial steps of immune enhancement observed in
      some patients with natural DV infection. They also demonstrate that using modern
      experimental technology, DV infection, and neutralization and enhancement of DV
      infection can be easily assessed simultaneously in multiple cell types.

PMID- 18041020
TI  - Higher risk of hepatitis C virus perinatal transmission from drug user mothers is
      mediated by peripheral blood mononuclear cell infection.
AB  - Maternal injection drug use and peripheral blood mononuclear cell infection by
      hepatitis C virus are important risk factors for perinatal transmission of the
      virus. The aim of present study was to evaluate the independent association of
      these two factors on perinatal transmission. Forty-eight consecutive mothers who
      transmitted infection to their offspring and 122 consecutive mothers who did not,
      together with their children, were examined. Both maternal injection drug use and
      peripheral blood mononuclear cell infection were significantly more frequent in
      infected than in uninfected children (respectively P = 0.04; odds ratio 2.33, 95%
      confidence intervals 1.02-5.42 and P < 10(-6); odds ratio and 95% confidence
      intervals not calculable due to zero values). Multivariate analysis confirmed the
      link between maternal peripheral blood mononuclear cell infection and perinatal
      transmission (P < 10(-6); odds ratio and 95% confidence intervals not calculable
      due to zero values) but no association was found with maternal injection drug
      use. The high risk of perinatal transmission found in injection drug use mothers
      is dependent on maternal peripheral blood mononuclear cell infection by hepatitis
      C virus. Peripheral blood mononuclear cell infection represents one of the most
      important risk factors for hepatitis C virus perinatal transmission.

PMID- 18041021
TI  - Development of a TaqMan assay for the six major genotypes of hepatitis C virus:
      comparison with commercial assays.
AB  - A quantitative real-time PCR assay was developed that detects genomic RNA from
      reference strains representing the six major genotypes of hepatitis C virus (HCV)
      with equal sensitivity and accurately measured HCV RNA in JFH1 HCV-infected
      Huh7.5 cells. The method is indirectly calibrated to the first international (WHO
      96/790) HCV standard preparation and has a linear dynamic range of 10(2.6)
      10(6.5) IU/ml. In addition, the inter- and intra-assay precision were
      approximately 3% CV and <2% CV, respectively. Comparison with results obtained by
      commercially available HCV RNA Nucleic Acid Technology kits (Versant HCV RNA 3.0
      b-DNA and Amplicor HCV Monitor), that also employ the WHO standard, allowed
      validation of the TaqMan assay against all major HCV genotypes. Both commercial
      methods detected HCV RNA over a wide dynamic range, but showed a consistent
      difference of about 0.3 log10 when evaluating samples of different HCV genotypes.
      The genome titers obtained with the three methods correlated with the infectivity
      titers previously determined for the HCV reference strains. TaqMan assays have
      become an essential tool to follow viral load in clinical samples and cell
      culture-based experiments and this technology offers significant advantages in
      linear dynamic range, sensitivity and customization.

PMID- 18041022
TI  - Pancreatic insufficiency after different resections for benign tumours.
AB  - BACKGROUND: Pancreatic resections for benign diseases may lead to long-term
      endocrine/exocrine impairment. The aim of this study was to compare postoperative
      and long-term results after different pancreatic resections for benign disease.
      METHODS: Between 1990 and 1999, 62 patients underwent pancreaticoduodenectomy
      (PD), 36 atypical resection (AR) and 64 left pancreatectomy (LP) for benign
      tumours. Exocrine and endocrine pancreatic function was evaluated by 72-h faecal
      chymotrypsin and oral glucose tolerance test. RESULTS: The incidence of
      pancreatic fistula was significantly higher after AR than after LP (11 of 36
      versus seven of 64; P = 0.028). The long-term incidence of endocrine pancreatic
      insufficiency was significantly lower after AR than after PD (P < 0.001).
      Exocrine insufficiency was more common after PD (P < 0.001) and LP (P = 0.009)
      than after AR. The probability of developing both endocrine and exocrine
      insufficiency was higher for PD and LP than for AR (32, 27 and 3 per cent
      respectively at 1 year; 58, 29 and 3 per cent at 5 years; P < 0.001). CONCLUSION:
      Different pancreatic resections are associated with different risks of developing
      long-term pancreatic insufficiency. AR represents the best option in terms of
      long-term endocrine and exocrine function, although it is associated with more
      postoperative complications.

PMID- 18041023
TI  - Spatial gradient effects of 120 mT static magnetic field on endothelial tubular
      formation in vitro.
AB  - This study investigated the spatial magnetic gradient effects of static magnetic
      fields (SMF) on endothelial tubular formation by applying the maximum spatial
      gradient to a target site of culture wells for cell growth. The respective
      maximum values of magnetic flux density (B(max)), magnetic flux gradient (G(max))
      and the magnetic force product of the magnetic flux density and its gradient (a
      parameter of magnetic force) were 120 mT, 28 mT/mm and 1428 mT(2)/mm. The effects
      of gradient SMF on tubular formation were compared with those of uniform SMF that
      has no spatial gradients on the entire bottom area of culture wells. Five
      experimental groups of 25 samples each were examined: (1) sham exposure
      (control); (2) peak gradient exposure in the peripheral part; (3) peak gradient
      exposure in the central part; (4) uniform exposure to 20 mT; (5) uniform exposure
      to 120 mT. The SMF or sham exposure was carried out for 10 days. Photomicrographs
      of tubular cells, immunostained with an anti-platelet-endothelial cell adhesion
      molecule-1 (PECAM-1 [CD31]) antibody as a pan-endothelial marker, were analyzed
      after the 10-day culture. Gradient SMF in the peripheral or central part was
      found to significantly promote tubular formation in terms of the area density and
      length of tubules in each peak gradient/force part of the wells, compared with
      the sham exposure. In contrast, uniform SMF did not induce any significant change
      in the tubular formation. These findings suggest that tubule formation can be
      promoted by applying the peak gradient/force to a target site of culture wells.

PMID- 18041025
TI  - Change in hepatitis C virus genotype in hemodialysis patients after end-of
      treatment response to interferon monotherapy--relapse or re-infection?
AB  - Hepatitis C virus (HCV) infection remains common among hemodialysis patients and
      its occurrence is related mainly to nosocomial spread. Although dialysis patients
      with HCV infection respond well to interferon-based therapy, relapse is frequent.
      This study aimed at a selected group of hemodialysis patients infected with HCV
      infection undergoing interferon therapy who achieved end-of-treatment virological
      response but became HCV-RNA positive again 6 months after end-of-treatment. It
      was evaluated whether de novo HCV-RNA positivity in these non-sustained
      responders occurred due to lack of clearance of HCV after the initial response to
      interferon-alpha (relapse) or due to re-infection with a new strain (re
      infection). Genotyping by Inno-LiPA and by phylogenetic tree analysis using
      partial HCV-NS5B sequences at two evaluation points: pre-treatment (T0) and 6
      months after end-of-treatment (T18). Non-sustained responders (n = 15) carried
      subtypes 1a (8 patients), 1b (4 patients), 3a (2 patients), and 4a (1 patient)
      before treatment. Identical subtypes were detected in 10 patients at T18. Five
      patients changed genotypes at T18, suggesting nosocomial re-infection. This study
      emphasizes the importance of epidemiologic measures to control the re-exposure of
      hemodialysis patients treated previously for HCV infection.

PMID- 18041024
TI  - Subgenotype diversity of hepatitis B virus American genotype F in Amerindians
      from Venezuela and the general population of Colombia.
AB  - The objective of this study was the evaluation of the genetic diversity found in
      HBV circulating among Venezuelan Amerindians and the general population in
      Colombia. Phylogenetic analysis of the S region in 194 isolates showed that
      genotype F is highly predominant in Colombia and Venezuela. This might be related
      to the genetic background of the population. F3 is the main subgenotype which
      circulates in both countries. Phylogenetic analysis of 61 complete genome
      sequences of HBV American genotypes confirms the presence of two genotypes F and
      H, and 4 F subgenotypes. In Venezuela, subgenotypes F1, F2, and F3 circulate in
      East and West Amerindians, while only F3 was found among South Amerindians.
      Japreira community derived from Yucpa Amerindians around 150 years ago. However,
      several Japreira HBV sequences were forming a clade that can be classified as
      subgenotype 2b, differing from Yucpa sequences that belong mainly to subgenotype
      F3. The apparent absence of correlation between the phylogenetic groupings of HBV
      isolates with the ethnical origin in aboriginal populations might be suggesting a
      recent origin of HBV American subgenotypes, or a genetic drift effect.

PMID- 18041026
TI  - A community-derived outbreak of adenovirus type 3 in children in Taiwan between
      2004 and 2005.
AB  - An outbreak of respiratory adenovirus infection in children was observed in
      northern Taiwan between November 2004 and February 2005. Using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the
      serotype(s) of 172 adenovirus isolates in the outbreak period, we found that
      adenovirus type 3 (Ad3) was the predominant type (87.2%), followed by Ad2 (6.4%),
      Ad1 (4.1%), Ad7 (1.2%), Ad4 (0.6%), and Ad5 (0.6%). The genotype of Ad3 was
      analyzed for 15 isolates from the outbreak period by RFLP of the full-length
      genome. All these isolates belonged to genotype Ad3a2. Compared with the Ad3
      infected patients in the baseline period, a significantly higher proportion of
      Ad3-infected patients in the outbreak period had severe infections (58.0% vs.
      40.2%, P = 0.01), which included bronchopneumonia (28.7%), exudative tonsillitis
      (24.1%), and tonsillitis (16.1%). Moreover, patients with severe infections were
      significantly younger than those without (4.10 vs. 8.15 years, P < 0.001). In
      summary, our study demonstrated that Ad3 was the predominant serotype responsible
      for the respiratory adenovirus outbreak in northern Taiwan during 2004-2005 and
      was associated with severe infections in the outbreak period.

PMID- 18041027
TI  - Chandipura virus: a major cause of acute encephalitis in children in North
      Telangana, Andhra Pradesh, India.
AB  - A hospital-based surveillance was undertaken between May 2005 and April 2006 to
      elucidate the contribution of Chandipura virus (CHPV) to acute viral encephalitis
      cases in children, seroconversion in recovered cases and to compare the
      seroprevalences of anti-CHPV IgM and N antibodies in areas reporting cases with
      those without any case of acute viral encephalitis. During this period, 90 cases
      of acute encephalitis were hospitalized in the pediatric wards of Mahatma Gandhi
      Memorial (MGM) Hospital, Warangal. There were 49 deaths (Case Fatality Rate,
      i.e., CFR of 54.4%). Clinical samples and records were obtained from 52 suspected
      cases. The cases were below 15 years, majority in 0-4 years (35/52, 67.3%).
      Computerized tomography (CT) scans and cerebro-spinal fluid (CSF) picture favored
      viral etiology. No neurological sequelae were observed. CHPV etiology was
      detected in 25 cases (48.1%, n = 52; RNA in 20, IgM in 3 and N antibody
      seroconversion in 2). JEV etiology was detected in 5 cases (IgM in 4 cases and
      seroconversion in 1 case). Anti-CHPV IgM seroprevalence in contacts (26/167,
      15.6%) was significantly higher (P < 0.05) than in non-contacts (11/430, 2.6%);
      which was also observed in children <15 years (19/90, 21.1% vs. 3/109, 2.7%).
      Anti-CHPV N antibody seroprevalence in <15 years contacts (66/90, 73.3%) and non
      contacts (77/109, 70.6%) was significantly lower (P < 0.05) than in contacts
      (75/77, 97.4%) and non-contacts (302/321, 94.1%) more than 15 years respectively.
      CHPV appears to be the major cause of acute viral encephalitis in children in
      endemic areas during early monsoon months.

PMID- 18041028
TI  - Novel anti-dengue monoclonal antibody recognizing conformational structure of the
      prM-E heterodimeric complex of dengue virus.
AB  - An interaction between the premembrane (prM) and envelope (E) glycoproteins as
      prM-E heterodimer is required for proper folding and transport of E during the
      formation and release of new flaviviral progeny. More evidence, however, is
      needed to confirm this interaction of prM and E during dengue virus replication.
      In this study, 2E11, a mouse monoclonal antibody (Mab) that specifically
      recognizes dengue prM-E heterodimeric complex in either intracellular or secreted
      dengue virions, was generated and characterized. In immunofluorescence and immuno
      pull down assays, the Mab 2E11 recognized an epitope present in 293T
      transfectants that co-expressed prM and the full-length form of E in cis and in
      trans, but it failed to react with prM or E protein expressed individually. The
      reactivity of Mab 2E11 was diminished in transfected cells that co-express prM
      together with a truncated form of E lacking the 84-residue stretch at the C
      terminal transmembrane region, presumably essential for prM and E interaction.
      The Mab 2E11 described in this study is a novel Mab with a unique capability in
      detecting the conformational structure of prM-E heterodimeric complex of dengue
      virus. It will be a new biological tool for identification and characterization
      of dengue prM-E heterodimer as well as virus maturation and export.

PMID- 18041029
TI  - Frequency and clinical significance of human beta-herpesviruses in cervical
      samples from Italian women.
AB  - Human papillomaviruses (HPVs) are necessary, but not sufficient, for the
      development of cervical cancer (CC). Human beta-herpesviruses (beta-HHVs) have
      been suggested as possible cofactors in the oncogenesis of CC. In this cross
      sectional study, the prevalence and possible association of cytomegalovirus
      (CMV), HHV-6 and -7 with HPV presence was investigated by quantitative real-time
      PCR assays in cervical samples obtained from 208 italian women. The two most
      common high-risk HPV types found were 31 and 16. Overall, the positive rates for
      CMV, HHV-6 and HHV-7 were 66%, 25%, and 6%, respectively. In particular, the
      prevalence of CMV was found to be extremely high irrespective of either the
      cytological category or HPV positivity. The prevalence of HHV-6 DNA was
      significantly higher in high-grade squamous intraepithelial lesions (HSIL)
      respect to normal women (P < 0.017); by contrast, the prevalence HHV-7 DNA was
      generally low and not associated with SIL. Copresence of CMV and HHV-6 DNA was
      found to be significantly higher in patients with SIL respect to normal women (P
      < 0.05). No correlation was demonstrated between the viral load of all three beta
      HHVs and the different cytological stages or with the HPV presence. A few
      patients with severe disease however showed very high viral loads which for HHV-6
      may be indicative of viral integration. In conclusion, this study suggests that
      CMV and HHV-7 alone are probably not implicated in the oncogenesis of CC whilst
      HHV-6 alone or together with CMV may contribute to the development of CC.

PMID- 18041030
TI  - Rapid and sensitive detection of metapneumovirus in clinical specimens by
      indirect fluorescence assay using a monoclonal antibody.
AB  - Human metapneumovirus, with two known genotypes named A and B, is associated with
      mild respiratory symptoms to severe LRTI in children, high-risk adults and the
      elderly. Rapid and reliable methods of hMPV detection in clinical samples are
      essential to implement appropriate care, to better understand the pathology of
      hMPV and to determine its epidemiology. Respiratory samples from 1,386 patients
      collected during 2 consecutive years were screened for hMPV using indirect
      immunofluorescence (IFA) assay with a monoclonal antibody. Forty-three patients
      tested positive for hMPV by the IFA method. In parallel, the samples were
      examined with RT-PCR on the F gene. Of these, 41 specimens were RT-PCR positive.
      The remaining two IF positives were cultured and the cultures were subsequently
      RT-PCR positive. IFA showed therefore a sensitivity of 100%. No false positive
      signals were obtained with the influenza virus, respiratory syncytial virus or
      parainfluenza. When tested by RT-PCR, all IFA-negative samples (n = 204)were
      found negative. Therefore the specificity of IFA was 100%, IC95 [98-100%], with a
      negative predictive value of 100%. Based upon phylogenetic analysis of the fusion
      gene, both subgroups of hMPV were efficiently detected by IFA, and the viral
      aetiology could be given in 2 hr. These results demonstrate the potential
      usefulness of immunofluorescence with our monoclonal antibody for the rapid
      detection of hMPV in clinical specimens in the management of therapy and the
      control of nosocomial diffusion.

PMID- 18041031
TI  - Detection of novel NF1 mutations and rapid mutation prescreening with
      Pyrosequencing.
AB  - Neurofibromatosis type 1 (NF1) is caused by mutations in the neurofibromin (NF1)
      gene. Mutation analysis of NF1 is complicated by its large size, the lack of
      mutation hotspots, pseudogenes and frequent de novo mutations. Additionally, the
      search for NF1 mutations on the mRNA level is often hampered by nonsense-mediated
      mRNA decay (NMD) of the mutant allele. In this study we searched for mutations in
      a cohort of 38 patients and investigated the relationship between mutation type
      and allele-specific transcription from the wild-type versus mutant alleles.
      Quantification of relative mRNA transcript numbers was done by Pyrosequencing, a
      novel real-time sequencing method whose signals can be quantified very
      accurately. We identified 21 novel mutations comprising various mutation types.
      Pyrosequencing detected a definite relationship between allelic NF1 transcript
      imbalance due to NMD and mutation type in 24 of 29 patients who all carried frame
      shift or nonsense mutations. NMD was absent in 5 patients with missense and
      silent mutations, as well as in 4 patients with splice-site mutations that did
      not disrupt the reading frame. Pyrosequencing was capable of detecting NMD even
      when the effects were only moderate. Diagnostic laboratories could thus exploit
      this effect for rapid prescreening for NF1 mutations as more than 60% of the
      mutations in this gene disrupt the reading frame and are prone to NMD.

PMID- 18041032
TI  - 2-D difference gel electrophoresis of the lung squamous cell carcinoma versus
      normal sera demonstrates consistent alterations in the levels of ten specific
      proteins.
AB  - Most lung cancers are diagnosed too late for curative treatment to be possible,
      therefore early detection is crucial. Serum proteins are a rich source of
      biomarkers and have the potential to be used as diagnostic and prognostic
      indicators for lung cancer. In order to examine differences in serum levels of
      specific proteins associated with human lung squamous carcinoma, immunodepletion
      of albumin and five other high-abundant serum proteins followed by 2-D difference
      gel electrophoresis (DIGE) analysis and subsequent MS was used to generate a
      panel of proteins found to be differentially expressed between the cancer and
      normal samples. Proteins found to have increased abundance levels in squamous
      cell carcinoma sera compared to normal sera included apolipoprotein A-IV
      precursor, chain F; human complement component C3c, haptoglobin, serum amyloid A
      protein precursor and Ras-related protein Rab-7b. Proteins found to have lower
      abundance levels in squamous cell carcinoma sera compared to normal sera included
      alpha-2-HS glycoprotein, hemopexin precursor, proapolipoprotein, antithrombin III
      and SP40; 40. The data presented here demonstrate that high-abundant protein
      removal combined with 2-D DIGE is a powerful strategy for the discovery of
      potential biomarkers. The identification of lung cancer-specific biomarkers is
      crucial to early detection, which in turn could lead to a dramatic increase in
      survival rates.

PMID- 18041033
TI  - Poly(gamma-glutamic acid) nanoparticles as an efficient antigen delivery and
      adjuvant system: potential for an AIDS vaccine.
AB  - Antigen delivery systems using polymeric nanoparticles are of special interest as
      stable protein-based antigen carriers. In the present study, novel biodegradable
      poly(gamma-glutamic acid) (gamma-PGA) nanoparticles were examined for their
      antigen delivery and immunostimulatory activities in vitro and in vivo. The
      uptake of ovalbumin by dendritic cells was markedly enhanced by gamma-PGA
      nanoparticles, and the ovalbumin was gradually released from gamma-PGA
      nanoparticles into the cells. In addition, gamma-PGA nanoparticles appeared to
      have great potential as an adjuvant, because they could induce the maturation of
      dendritic cells. Although not only ovalbumin-encapsulating nanoparticles (OVA
      NPs) but also a simple mixture of ovalbumin and nanoparticles induced dendritic
      cell maturation, the only dendritic cells exposed to OVA-NPs could strongly
      activate antigen-specific interferon (IFN)-gamma-producing T cells. Subcutaneous
      immunization of mice with human immunodeficiency virus type 1 (HIV-1) p24
      encapsulating nanoparticles activated antigen-specific IFN-gamma-producing T
      cells in spleen cells and induced p24-specific serum antibodies, as compared to
      immunization with p24 alone. Like ovalbumin, a mixture of p24 and nanoparticles
      also induced antigen-specific serum antibodies but did not activate IFN-gamma
      producing T cells in spleen cells, suggesting that nanoparticles play a critical
      role in inducing cellular immune responses. Furthermore, gamma-PGA nanoparticles
      had a capacity comparable to that of the complete Freund's adjuvant (CFA) in
      inducing p24-specific serum antibody. However, unlike CFA, they predominantly
      activated p24-specific IFN-gamma-producing T cells. Thus, gamma-PGA nanoparticles
      encapsulating various antigens may have great potential as novel and efficient
      protein-based vaccines against infectious diseases, including HIV-1 infection.

PMID- 18041034
TI  - Identification and analysis of alpha1,6-fucosylated proteins in human normal
      liver tissues by a target glycoproteomic approach.
AB  - alpha1,6-Fucose residues within the N-glycan core structures were commonly
      observed in many glycoproteins. Our previous studies showed that aberrantly
      alpha1,6-fucosylated glycoproteins might be associated with metastasis of
      hepatocellular carcinoma (HCC). Little is known about human normal liver tissues
      (HNLTs) in the literatures. In this study, a target glycoproteomic approach which
      consists of lectin-affinity chromatography, 2-DE, protein immunoprecipitation and
      lectin blot, and MALDI-MS/MS, was utilized to screen physiologically alpha1,6
      fucosylated glycoproteins. Lens culinaris agglutinin (LCA)-affinity glycoprotein
      profiles of HNLT were established and analyzed, which allowed identification of
      53 proteins by MS analysis, including haptoglobin precursor, alpha-enolase, etc.
      Gene ontology (GO) annotation proved that these proteins distribute predominately
      in organelle and play crucial roles in binding and catalytic reactions. The
      present methodology enabled the identification of all the specific subsets of
      glycoprotein, and the corresponding data could contribute to the finding of more
      aberrantly alpha1,6-fucosylated glycoproteins related to liver diseases.

PMID- 18041035
TI  - Monoclonal antibody proteomics: discovery and prevalidation of chronic
      obstructive pulmonary disease biomarkers in a single step.
AB  - We define mAb proteomics as the global generation of disease specific antibodies
      that permit mass screening of biomarkers. An integrated, high-throughput, disease
      specific mAb-based biomarker discovery platform has been developed. The approach
      readily provided new biomarker leads with the focus on large-scale discovery and
      production of mAb-based, disease-specific clinical assay candidates. The outcome
      of the biomarker discovery process was a highly specific and sensitive assay,
      applicable for testing of clinical validation paradigms, like response to
      treatment or correlation with other clinical parameters. In contrast to MS-based
      or systems biology-based strategies, our process produced prevalidated clinical
      assays as the outcome of the discovery process. By re-engineering the biomarker
      discovery paradigm, the encouraging results presented in this paper clearly
      demonstrate the efficiency of the mAb proteomics approach, and set the grounds
      for the next steps of studies, namely, the hunt for candidate biomarkers that
      respond to drug treatment.

PMID- 18041036
TI  - Porous silicon surfaces: a candidate substrate for reverse protein arrays in
      cancer biomarker detection.
AB  - This paper introduces a new substrate for reverse-phase protein microarray
      applications based on macroporous silicon. A key feature of the microarray
      substrate is the vastly surface enlarging properties of the porous silicon, which
      simultaneously offers highly confined microarray spots. The proof of principle of
      the reverse array concept was demonstrated in the detection of different levels
      of cyclin E, a possible cancer biomarker candidate which regulates G1-S
      transition and correlates with poor prognosis in different types of human
      cancers. The substrate properties were studied performing analysis of total
      cyclin E expression in human colon cancer cell lines Hct116 and SW480. The
      absence of unspecific binding and good microarray quality was demonstrated. In
      order to verify the performance of the 3-D textured macroporous surface for
      complex biological samples, lysates of the human tissue spiked to different
      levels with cell extract overproducing cyclin E (Hct116) were arrayed on the chip
      surface. The samples were spotted in a noncontact mode in 100 pL droplets with
      spots sizes ranged between 50 and 70 mum and spot-to-spot center distances 100
      mum, allowing microarray spot densities up to 14 000 spots per cm(2). The
      different sample types of increasing complexities did not have any impact on the
      spot intensities recorded and the protein spots showed good homogeneity and
      reproducibility over the recorded microarrays. The data demonstrate the potential
      use of macroporous silicon as a substrate for quantitative determination of a
      cancer biomarker cyclin E in tissue lysates.

PMID- 18041037
TI  - Adaptation of the "in-gel release method" to N-glycome analysis of low-milligram
      amounts of material.
AB  - Protein N-glycosylation is a post-translational modification which plays numerous
      crucial physiological roles. The N-glycan pattern varies depending on the species
      organs, tissues and even cell types and their respective physiological states.
      Obtaining enough starting material from a particular cell type or tissue for N
      glycan purification by conventional methods can, in certain cases, be very
      difficult. Previously, a sensitive technique, the "in-gel release method" that
      allows the determination of N-glycans attached to a protein isolated by SDS-PAGE,
      has been developed in this and other laboratories. Here, we describe the
      adaptation of this method to obtain information on the N-glycome from minute
      amounts of tissue. The starting material, ranging from less than a milligram to a
      few milligrams of fresh tissue, is directly ground in Laemmli sample buffer and
      subject briefly to discontinuous Tris-glycine-SDS-PAGE. The Coomassie-stained
      band containing the majority of the proteins is subject to the "in-gel release
      method". The developed technique was used to analyze N-glycan patterns of
      different samples from Caenorhabditis elegans, Drosophila melanogaster,
      Spodoptera frugiperda, Trichoplusia ni, Nicotiana benthamiana, Arabidopsis
      thaliana, and Mus musculus. Furthermore, the technique was used to determine the
      effects of transient small-scale RNAi-mediated knock-down of a glycosylation
      related gene in Drosophila Schneider 2 cell line.

PMID- 18041038
TI  - Chip-LC-MS for label-free profiling of human serum.
AB  - The discovery of biomarkers in easily accessible body fluids such as serum is one
      of the most challenging topics in proteomics requiring highly efficient
      separation and detection methodologies. Here, we present the application of a
      microfluidics-based LC-MS system (chip-LC-MS) to the label-free profiling of
      immunodepleted, trypsin-digested serum in comparison to conventional capillary LC
      MS (cap-LC-MS). Both systems proved to have a repeatability of approximately 20%
      RSD for peak area, all sample preparation steps included, while repeatability of
      the LC-MS part by itself was less than 10% RSD for the chip-LC-MS system.
      Importantly, the chip-LC-MS system had a two times higher resolution in the LC
      dimension and resulted in a lower average charge state of the tryptic peptide
      ions generated in the ESI interface when compared to cap-LC-MS while requiring
      approximately 30 times less (~5 pmol) sample. In order to characterize both
      systems for their capability to find discriminating peptides in trypsin-digested
      serum samples, five out of ten individually prepared, identical sera were spiked
      with horse heart cytochrome c. A comprehensive data processing methodology was
      applied including 2-D smoothing, resolution reduction, peak picking, time
      alignment, and matching of the individual peak lists to create an aligned peak
      matrix amenable for statistical analysis. Statistical analysis by supervised
      classification and variable selection showed that both LC-MS systems could
      discriminate the two sample groups. However, the chip-LC-MS system allowed to
      assign 55% of the overall signal to selected peaks against 32% for the cap-LC-MS
      system.

PMID- 18041041
TI  - Biomarker discovery and related topics.

PMID- 18041042
TI  - Racing pigeon identification using STR and chromo-helicase DNA binding gene
      markers.
AB  - Pigeon racing appeals to many in Taiwan, due in part to the potential large
      financial gains based on illegal betting. The races are unregulated with frequent
      examples of fraud, such as substitution of one bird for a substandard one. There
      is no test available to reliably verify the bloodline of pigeons and thus help to
      resolve such disputes. In this study, we describe a multiplex PCR amplification
      system combining 7 STR loci and a chromo-helicase DNA binding gene (CHD) marker
      for the identification of individual pigeons. The cumulative power of
      discrimination (CPd) of the 7 STR loci was 0.99999234 based upon our population
      study. The cumulative probability of paternity (CPP) when used in paternity
      testing of 17 pigeon families ranged from 97.36 to 99.99% and the combined
      probability of exclusion (CPE) was 0.9325 for these seven STR markers. The
      statistical data illustrates the potential of this system to be used in pigeon
      individualization and paternity testing. Furthermore, the established STR system
      could be also used in the other areas, such as ecology, population genetics, and
      avian breeding programs.

PMID- 18041043
TI  - Relationship of serological subtype, basic core promoter and precore mutations to
      genotypes/subgenotypes of hepatitis B virus.
AB  - Using phylogenetic analysis and pairwise comparison of 670 complete hepatitis B
      virus (HBV) genomes, we demonstrated that nucleotide divergence greater than 7.5%
      can be used to separate strains into genotypes A-H. Strains can be separated into
      subgenotypes when two criteria are met: nucleotide divergence of about 4% but
      less than 7.5% and good bootstrap support. There is a highly statistically
      significant association between serological subtypes and genotypes (chi2-test for
      association, P < 0.0001): adw is associated with genotypes A, B, F, G, and H, adr
      with C and ayw with D and E. The logistic regression method showed that 1802
      1803CG are characteristic of genotypes A, D, and E whereas 1802-1803TT are
      characteristic of genotypes B, C, and F. 1858C is positively associated with
      genotypes A, F, and H and 1858T with genotypes B, D, and E. Subgenotypes C2,
      F1/F4 can be differentiated from subgenotypes C1, F2/F3, respectively, because
      the latter have 1858C as opposed to 1858T in the former. 1888A was positively
      associated with subgenotype A1 and TAA at 1817 with genotype G. The Haploplot
      method revealed high linkage between loci 1858 and 1896 but strong evidence of
      recombination between loci 1862 and 1896. Loci 1809-1812, 1862, and 1888 may have
      co-evolved. Using a computer program, we showed that serological subtype deduced
      from the S region (position 155-835) and mutations/variations within the basic
      core promoter/precore region (1653-1900), allowed genotyping of HBV with 97%
      sensitivity and 99% specificity. Certain subgenotypes or subgenotype groups could
      also be differentiated.

PMID- 18041044
TI  - Molecular epidemiology and disease severity of respiratory syncytial virus in
      relation to other potential pathogens in children hospitalized with acute
      respiratory infection in Jordan.
AB  - Human respiratory syncytial virus (HRSV) is the major viral cause of acute lower
      respiratory tract infections in children. Few data about the molecular
      epidemiology of respiratory syncytial virus in developing countries, such as
      Jordan, are available. The frequency and severity of infections caused by HRSV
      were assessed in hospitalized Jordanian children <5 years of age compared with
      other potential etiological agents. Overall a potential pathogen was detected in
      78% (254/326) of the children. HRSV was detected in 43% (140/326) of the
      nasopharyngeal aspirates. HRSV was found more frequently during the winter
      (January/February), being less frequent or negligible by spring (March/April).
      Analysis of 135 HRSV-positive strains using restriction fragment length
      polymorphism showed that 94 (70%) belonged to subgroup A, and 41 (30%) to
      subgroup B. There were also two cases of mixed genotypic infection. Only four of
      the six previously described N genotypes were detected with NP4 predominating.
      There were no associations between subgroup or N-genogroup and disease severity.
      HRSV was significantly associated with more severe acute respiratory infection
      and the median age of children with HRSV was lower than for those without. Next
      in order of frequency were adenovirus (116/312: 37%), human bocavirus (57/312:
      18%), rhinovirus (36/325: 11%), Chlamydia spp. (14/312: 4.5%), human
      metapneumovirus (8/326: 2.5%), human coronavirus NL63 (4/325: 1.2%), and
      influenza A virus (2/323: 0.6%). Influenza B; parainfluenza viruses 1-4, human
      coronavirus HKU1 and Mycoplasma pneumoniae were not detected.

PMID- 18041045
TI  - Impact of HIV-1 genetic diversity in China on the measurement of viral load.
AB  - In this study, 190 HIV-positive samples were collected from different regions of
      China. The HIV clades of 153 samples were determined successfully based on env
      sequencing. Specifically, 48, 5, 87, and 13 isolates belonged to clades B', B,
      BC, and AE, respectively. The viral loads in all samples were measured using
      three commercial assays, Amplicor HIV-1 monitor v1.5, Nuclisens HIV-1 QT and
      NucliSens EasyQ HIV-1 assays. The differences and linear correlations for
      individual assays were compared, with expected 1:1 relationships. Significant
      differences were found for the following viral loads: clade BC measured by any
      two assays (P < 0.001); clade AE between Amplicor 1.5 and Easy Q (P = 0.005);
      clade B' between Amplicor 1.5 and Nuclisens QT (P = 0.002); clade AE between
      Amplicor 1.5 and Nuclisens QT (P = 0.025); and clade B' between Amplicor 1.5 and
      EasyQ (P = 0.04). The largest mean difference in the log(10) values was 0.9518,
      which was found between Amplicor 1.5 and Nuclisens QT. However, the viral loads
      for clades AE and B' measured by EasyQ and Nuclisens QT, and those for clade B
      measured by any two assays did not differ significantly. The degrees of
      correlation for clades B and B' between any two assays (R > 0.8) were higher that
      those for clades AE and BC between any two assays (R < 0.7), except for clade AE
      between Amplicor 1.5 and Easy Q. Thus, the clade types, especially clades BC and
      AE, are most likely to impact on the quantitation of viral load using
      differentassays.

PMID- 18041046
TI  - Post-exposure prophylaxis with a maraviroc-containing regimen after occupational
      exposure to a multi-resistant HIV-infected source person.
AB  - We report the case of a health care worker who received a post-exposure
      prophylaxis including an investigational drug, maraviroc, after a needle stick
      percutaneous injury to an HIV-infected patient with late-stage disease and
      harboring a multi-drug resistant virus. Post-exposure prophylaxis including
      maraviroc was pursued for a total of 28 days, with a weekly clinical and
      biological evaluation. Post-exposure prophylaxis was well tolerated, with no
      increase in liver function tests. The health care worker remained HIV-negative
      after a 6-month follow-up.

PMID- 18041047
TI  - Joint modelling of repeated measurements and time-to-event outcomes: the fourth
      Armitage lecture.
AB  - In many longitudinal studies, the outcomes recorded on each subject include both
      a sequence of repeated measurements at pre-specified times and the time at which
      an event of particular interest occurs: for example, death, recurrence of
      symptoms or drop out from the study. The event time for each subject may be
      recorded exactly, interval censored or right censored. The term joint modelling
      refers to the statistical analysis of the resulting data while taking account of
      any association between the repeated measurement and time-to-event outcomes. In
      this paper, we first discuss different approaches to joint modelling and argue
      that the analysis strategy should depend on the scientific focus of the study. We
      then describe in detail a particularly simple, fully parametric approach.
      Finally, we use this approach to re-analyse data from a clinical trial of drug
      therapies for schizophrenic patients, in which the event time is an interval
      censored or right-censored time to withdrawal from the study due to adverse side
      effects.

PMID- 18041048
TI  - Morphogenic machines evolve more rapidly than the signals that pattern them:
      lessons from amphibians.
AB  - The induction of mesoderm and the patterning of its dorsal-ventral and anterior
      posterior axes seems to be relatively conserved throughout the chordates, as do
      the morphogenic movements that produce a phylotypic stage embryo. What is not
      conserved is the initial embryonic architecture of the fertilized egg, and the
      specific cell behaviors used to drive mesoderm morphogenesis. How then do
      conserved patterning pathways adapt to diverse architectures and where do they
      diverge to direct the different cell behaviors used to shape the phylotypic body
      plan? Amphibians in particular, probably because of their broad range of
      reproductive strategies, show diverse embryonic architectures across their class
      and use diverse cell behaviors during their early morphogenesis, making them an
      interesting comparative group. We examine three examples from our work on
      amphibians that show variations in the use of cell behaviors to drive the
      morphogenesis of the same tissues. We also consider possible points where the
      conserved patterning pathways might diverge to produce different cell behaviors.

PMID- 18041049
TI  - Comments on 'Evaluating the added predictive ability of a new marker' by M.
      Pencina, R. D'Agostino, R. D'Agostino Jr, R. Vasan, Statistics in Medicine (DOI:
      10.1002/sim.2929).

PMID- 18041050
TI  - Slower conduction velocity and motor unit discharge frequency are associated with
      muscle fatigue during isometric exercise in type 1 diabetes mellitus.
AB  - Type 1 diabetes mellitus (T1DM) is associated with a peripheral neuropathy that
      reduces nerve conduction velocity. This may impair high motor-unit discharge
      frequencies (MUDF), decrease muscle activation, and curtail the ability to
      sustain repetitive contractile tasks. We examined (1) whether MUDF, the
      contractile properties of the knee extensors, and the conduction velocity of
      persons with T1DM differed from controls; (2) whether persons with T1DM can
      maintain adequate MUDF during a fatigue protocol; and (3) the relationship
      between these parameters and impaired glycemic control. We studied male and
      female subjects with T1DM and controls matched for age, height, weight, and
      gender. Single motor unit recordings were made from vastus lateralis during
      maximal and submaximal contractions and during a fatigue protocol. Glycemic
      control was assessed from blood glucose concentration and glycosylated hemoglobin
      (HbA1c). Control femoral conduction velocities were comparable to literature
      values and those of the T1DM subjects were slower. These values correlated with
      plasma glucose and HbA1c. T1DM subjects fatigued 45% sooner than controls, and
      time to fatigue and conduction velocity were correlated (r = 0.54, P < 0.05).
      Discharge frequencies tended to be slower during 50% maximal voluntary
      contractile force in the T1DM subjects at task failure. Persons with T1DM had
      slower conduction velocities and lower MUDF than their controls, which apparently
      leads to impaired activation of muscle and decreased endurance during isometric
      fatigue.

PMID- 18041052
TI  - Tumor necrosis factor-alpha antagonists and neuropathy.
AB  - Tumor necrosis factor (TNF)-alpha plays an important role in many aspects of
      immune system development, immune-response regulation, and T-cell-mediated tissue
      injury. The evidence that TNF-alpha, released by autoreactive T cells and
      macrophages, may contribute to the pathogenesis of immune-mediated demyelinating
      neuropathies is reviewed. TNF-alpha antagonists (infliximab, etanercept,
      adalimumab) are indicated for the treatment of advanced inflammatory rheumatic
      and bowel disease, but these drugs can induce a range of autoimmune diseases that
      also attack the central and peripheral nervous systems. Case histories and series
      report on the association between anti-TNF-alpha treatment and various disorders
      of peripheral nerve such as Guillain-Barre syndrome, Miller Fisher syndrome,
      chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy
      with conduction block, mononeuropathy multiplex, and axonal sensorimotor
      polyneuropathies. The proposed pathogeneses of TNF-alpha-associated neuropathies
      include both a T-cell and humoral immune attack against peripheral nerve myelin,
      vasculitis-induced nerve ischemia, and inhibition of signaling support for axons.
      Most neuropathies improve over a period of months by withdrawal of the TNF-alpha
      antagonist, with or without additional immune-modulating treatment. Preliminary
      observations suggest that TNF-alpha antagonists may be useful as an antigen
      nonspecific treatment approach to immune-mediated neuropathies in patients with a
      poor response to, or intolerance of, standard therapies, but further studies are
      required.

PMID- 18041051
TI  - Myostatin blockade improves function but not histopathology in a murine model of
      limb-girdle muscular dystrophy 2C.
AB  - Myostatin is a negative regulator of skeletal muscle growth. Myostatin mutations
      and pharmacological strategies increase muscle mass in vivo, suggesting that
      myostatin blockade may prove useful in diseases characterized by muscle wasting,
      such as the muscular dystrophies. We subjected the gamma-sarcoglycan-deficient
      (Sgcg(-/-)) mouse model of limb-girdle muscular dystrophy (LGMD) 2C to antibody
      mediated myostatin blockade in vivo. Myostatin inhibition led to increased fiber
      size, muscle mass, and absolute force. However, no clear improvement in muscle
      histopathology was evident, demonstrating discordance between physiological and
      histological improvement. These results and previous studies on the dyw/dyw mouse
      model of congenital muscular dystrophy and in the late-stage delta-sarcoglycan
      deficient (Sgcd(-/-)) mouse model of LGMD2F document disease-specific limitations
      to therapeutic strategies based on myostatin blockade in the more severe mouse
      models of different muscular dystrophies.

PMID- 18041053
TI  - Paradoxical depolarization of BA2+- treated muscle exposed to low extracellular
      K+: insights into resting potential abnormalities in hypokalemic paralysis.
AB  - The combination of sarcolemmal depolarization and hypokalemia exhibited by the
      different forms of hypokalemic paralysis has been attributed to abnormalities of
      the K+ conductance governing the resting membrane potential (V(REST)). Supportive
      data have been observed in muscle fibers biopsied from patients with familial
      hypokalemic periodic paralysis (HypoPP) that paradoxically depolarize at low K+.
      Although this observation is consistent with anomalous K+ conductance, rigorous
      experimental support is lacking. To establish a foundation for understanding the
      pathophysiology of hypokalemic paralysis, we studied Ba2+-treated muscle fibers
      under voltage clamp. As anticipated, Ba2+ blocked inward rectifying K+ (IRK)
      currents, and thereby promoted depolarization, supporting the notion that the IRK
      conductance governs V(REST). The IRK conductance also declined when muscle was
      challenged with reduced external K+. When the external K+ declined below 1 mM,
      V(REST) became uncoupled from the K+ reversal potential and depolarized. Partial
      ( approximately 50%) block of the IRK conductance with Ba2+ potentiated this
      uncoupling threshold, such that depolarization could be elicited by exposure to 2
      mM external K+. A quantitative computer model of resting ionic conductances was
      constructed, and simulations demonstrated that small alterations to resting
      conductances, such as adding a low-amplitude aberrant inward current flowing
      through "gating pores" in mutant Na+ channels causing HypoPP-2, can promote
      paradoxical depolarization in low K+. These findings offer a simple explanation
      for some of the heretofore poorly understood physiological abnormalities of
      HypoPP muscle and support the notion that pathological gating pore leakage
      currents may directly predispose to paralytic attacks.

PMID- 18041054
TI  - Effects of high-intensity focused ultrasound on nerve conduction.
AB  - The effects of various exposures (intensity, duration) of high-intensity focused
      ultrasound (HIFU) on sciatic nerve conduction were investigated in vivo in rats.
      The objective was to identify HIFU exposures that produce biological effects
      ranging from partial to complete conduction block, indicating potential use of
      HIFU as an alternative to current clinical methods of inducing nerve conduction
      block. In the study, 26 nerves were exposed and treated with 5-s applications of
      5.7-MHZ HIFU with acoustic intensities of 390, 2,255, 3,310, and 7,890 W/cm(2)
      (spatial peak, temporal peak). Compound muscle action potentials (CMAPs), in
      response to electrical stimulation of the nerve proximal to the HIFU site, were
      recorded from the plantar foot muscles immediately before and after HIFU
      treatment and 2 and 4 h after treatment. Furthermore, a preliminary long-term
      investigation was performed on 27 nerves with the same four sets of HIFU
      parameters. CMAPs were measured at the survival endpoint for each animal (7 or 28
      days after treatment). For nerves treated with the three lower exposures, CMAPs
      decreased initially within 4 h or 7 days after HIFU treatment and then recovered
      to their baseline level at 28 days after treatment. For the highest exposure,
      however, CMAPs remained absent even 28 days after treatment. These exposure
      dependent effects of HIFU on nerve function suggest its future potential as a
      novel treatment for severe spasticity and pain.

PMID- 18041055
TI  - Epithelial type, ingression, blastopore architecture and the evolution of
      chordate mesoderm morphogenesis.
AB  - Chordate embryos show an evolutionary trend in the mechanisms they use to
      internalize presumptive mesoderm, relying predominantly on invagination in the
      basal chordates, varying combinations of involution and ingression in the
      anamniote vertebrates and reptiles, and predominantly on ingression in birds and
      mammals. This trend is associated with variations in epithelial type and changes
      in embryonic architecture as well as variations in the type of blastopore formed
      by an embryo. We also note the surprising conservation of the involution, during
      gastrulation, of at least a subset of the notochordal cells throughout the
      chordates, and suggest that this indicates a constraint on morphogenic evolution
      based on a functional linkage between architecture and patterning. Finally, we
      propose a model for the evolutionary transitions from gastrulation through a
      urodele amphibian-type blastopore to gastrulation through a primitive streak, as
      in chick or mouse.

PMID- 18041056
TI  - VEGF and VEGFR-1 are coexpressed by epithelial and stromal cells of renal cell
      carcinoma.
AB  - BACKGROUND: Tumor angiogenesis is a dynamic process that plays a major role in
      cancer progression. Vascular endothelial growth factor (VEGF) and its receptors
      play a pivotal role in angiogenesis. The expression of VEGF and its receptors
      VEGFR-1 and VEGFR-2 in renal cell carcinoma (RCC) was investigated in the
      perspective of anti-VEGF treatments. METHODS: Total VEGF protein levels were
      quantified by enzyme-linked immunosorbent assay (ELISA) in tumor tissue samples
      from surgical specimens of 65 patients with clear cell RCC. At the cellular level
      the VEGF isoforms VEGFR-1 and VEGFR-2 mRNA were quantified by real-time
      quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in laser
      microdissected tumoral epithelial as stromal cells and in corresponding normal
      tissue compartments. Colocalization of VEGF and VEGFR-1 proteins was studied by
      triple immunofluorescent labeling. RESULTS: Protein VEGF in cytosolic extracts
      was significantly higher in tumoral than in nontumoral tissue (P< .0001). Event
      free survival was significantly longer for patients with cytosolic VEGF lower
      than the cutoff (75th percentile of VEGF protein levels, P= .02). In laser
      microdissected epithelial cells, VEGF(121) and VEGFR-1 mRNA expressions were
      higher in RCC than in corresponding nontumoral kidney (P= .007 and P= .002,
      respectively); they were also higher in stromal cells of RCC compared with
      nontumoral kidney (P= .02 and P= .003, respectively). There was no differential
      VEGFR-2 expression in epithelial or in stromal cells of tumoral or nontumoral
      kidney. By immunofluorescent labeling VEGF and VEGFR-1 colocalized on RCC tumor
      epithelial and stromal cells. CONCLUSIONS: Combined laser microdissection and
      quantitative RT-PCR, as triple immunofluorescent labeling, underlined the
      preferential expression of the most soluble VEGF isoform, VEGF(121), and its
      receptor VEGFR-1, but not VEGFR-2, in epithelial and stromal cells of RCC.

PMID- 18041058
TI  - Passive smoking and the use of noncigarette tobacco products in association with
      risk for pancreatic cancer: a case-control study.

PMID- 18041059
TI  - Do adjuvant aromatase inhibitors increase the cardiovascular risk in
      postmenopausal women with early breast cancer? Meta-analysis of randomized
      trials.
AB  - BACKGROUND: Despite the advantages from using aromatase inhibitors (AIs) compared
      with tamoxifen for early breast cancer, an unexpectedly greater number of grade 3
      and 4 cardiovascular events (CVAE) (as defined by National Cancer Institute of
      Canada-Common Toxicity Criteria [version 2.0] was demonstrated. METHODS: Phase 3
      randomized clinical trials (RCTs) comparing AI with tamoxifen in early breast
      cancer were considered eligible for this review. The event-based risk ratios
      (RRs) with 95% confidence intervals (95% CIs) were derived, and a test of
      heterogeneity was applied. Finally, absolute differences (ADs) in event rates and
      the number of patients needed to harm 1 patient (NNH) were determined. RESULTS:
      Seven eligible RCTs (19,818 patients) reported CVAE results. When considering all
      RCTs, the AD of the primary endpoint (CVAE) between the 2 arms (0.52%), tamoxifen
      versus AI, was statistically significant (RR, 1.31; 95% CI, 1.07-1.60; P= .007).
      This translated into an NNH value of 189 patients; when only third-generation AIs
      were considered, the difference (0.57%) remained significant (RR, 1.34; 95% CI,
      1.09-1.63; P= .0038). Thromboembolic events were significantly more frequent in
      the tamoxifen arm, regardless of the strategy adopted (RR, 0.53; 95% CI, 0.42
      0.65; P< .0001), without significant heterogeneity (P= .21). An AD of 1.17% and
      an NNH value of 85 patients were observed. CONCLUSIONS: According to the results
      from this meta-analysis, the risk of grade 3 and 4 CVAEs in patients who were
      receiving AIs was higher compared with the risk in patients who were receiving
      tamoxifen, and the difference reached statistical significance. However, the AD
      was relatively low, and from 160 to 180 patients had to be treated to produce 1
      event.

PMID- 18041060
TI  - Application of distance matrices to define associations between acute toxicities
      in colorectal cancer patients receiving chemotherapy.
AB  - BACKGROUND: Colorectal cancer patients undergoing chemotherapy (CT) are likely to
      experience multiple concurrent toxicities that, rather than appearing singularly,
      may be associated with one another. Graphic and tabular representations of
      distance matrices were used to identify associations between toxicities and to
      define the strengths of these relations. METHODS: Using a standardized data
      collection tool, electronic medical charts of 300 consecutive patients receiving
      either the combination of leucovorin, 5-fluorouracil (5-FU), and oxaliplatin
      (FOLFOX); the combination of leucovorin, 5-FU, and irinotecan (FOLFIRI); or 5-FU)
      were retrospectively reviewed to record baseline demographic and clinical
      information. Treatment-related toxicities were recorded using National Cancer
      Institute Common Toxicity Criteria during the first cycle of CT. Using a distance
      matrix approach, an analysis of CT-induced toxicity associations was elaborated.
      RESULTS: The graphic analysis, in which associations between toxicities were
      represented as links, identified 6 major hubs (fever, dehydration, fatigue,
      anorexia, pain, and weight loss), defined as central nodes with more connections
      than expected by chance. These were highly linked with minor nodes and provided
      evidence suggesting the existence of symptom clusters associated with CT-induced
      toxicities. CONCLUSIONS: The application of distance matrix analyses to define CT
      induced toxicity associations is new. The technique was effective in defining the
      global landscape of the binary relations among toxicities associated with Cycle 1
      therapy. The coherent clinical picture emerging from the network provides a
      strong suggestion that the toxicities in each cluster share a common
      pathobiologic basis, which may provide an opportunity for intervention. These
      findings could become useful for the early prediction of co-occurring toxicities
      and, in the future, as a phenotyping framework for the pharmacogenomic analysis
      of individual responses to chemotherapy.

PMID- 18041061
TI  - Structural and thermodynamic encoding in the sequence of rat microsomal
      cytochrome b(5).
AB  - The water-soluble domain of rat microsomal cytochrome b(5) is a convenient
      protein with which to inspect the connection between amino acid sequence and
      thermodynamic properties. In the absence of its single heme cofactor, cytochrome
      b(5) contains a partially folded stretch of 30 residues. This region is
      recognized as prone to disorder by programs that analyze primary structures for
      such intrinsic features. The cytochrome was subjected to amino acid replacements
      in the folded core (I12A), in the portion that refolds only when in contact with
      the heme group (N57P), and in both (F35H/H39A/L46Y). Despite the difficulties
      associated with measuring thermodynamic quantities for the heme-bound species, it
      was possible to rationalize the energetic consequences of both types of
      replacements and test a simple equation relating apoprotein and holoprotein
      stability. In addition, a phenomenological relationship between the change in
      T(m) (the temperature at the midpoint of the thermal transition) and the change
      in thermodynamic stability determined by chemical denaturation was observed that
      could be used to extend the interpretation of incomplete holoprotein stability
      data. Structural information was obtained by nuclear magnetic resonance
      spectroscopy toward an atomic-level analysis of the effects.

PMID- 18041062
TI  - Combined effect of the DeltaPhe or DeltaAla residue and the p-nitroanilide group
      on a didehydropeptides conformation.
AB  - Two series of dehydropeptides of the general formulae Boc-Gly-X-Phe-p-NA, Boc-Gly
      Gly-X-Phe-p-NA, Gly-X-Gly-Phe-p-NA.TFA, and Boc-Gly-X-Gly-Phe-p-NA, with X =
      Delta(Z)Phe and DeltaAla, were studied with NMR in DMSO and CDCl(3)-DMSO, and
      with CD in MeOH, MeCN, and TFE. The NMR spectra measured in DMSO suggest that
      peptides with the DeltaPhe residue next to Phe are folded whereas peptides with
      Gly between DeltaPhe and Phe are less ordered. NMR spectra of DeltaAla-containing
      peptides indicate that these peptides are flexible and their conformational
      equilibria are populated by many different conformations. The CD spectra show
      that conformational properties of the peptides studied are distinctly influenced
      by a mutual position of the dehydroamino acid residue and the p-NA group. They
      indicate that all dehydropeptides with the DeltaPhe residue, Boc-Gly-DeltaAla-Phe
      p-NA, and Boc-Gly-Gly-DeltaAla-Phe-p-NA adopt ordered conformations in all
      solvents studied, presumably of the beta-turn type. The last two peptides exhibit
      surprising chiroptical properties. Their spectra show exciton coupling-like
      couplets in the region of the p-NA group absorption. This shape of CD spectra
      suggests a rigid, chiral conformation with a fixed disposition of the p-NA group.
      The CD spectra indicate that Boc-Gly-DeltaAla-Gly-Phe-p-NA and Gly-DeltaAla-Gly
      Phe-p-NA.TFA are unordered, independently of the solvent.

PMID- 18041064
TI  - Development of sorafenib and other molecularly targeted agents in hepatocellular
      carcinoma.
AB  - It is well appreciated that hepatocellular carcinoma (HCC) represents one of the
      most challenging malignancies of worldwide importance. In fact, HCC is the fifth
      most common cancer and the third most common cause of cancer-related death
      globally. The incidence rates for HCC in the U.S. and Western Europe have been
      rising. Unresectable or metastatic HCC carries a poor prognosis, and systemic
      therapy with cytotoxic agents provides marginal benefit. Because of the poor
      track record of systemic therapy in HCC, there has been a sense of nihilism for
      this disease in the oncology community for decades. However, with the arrival of
      newly developed, molecularly targeted agents and the success of some of these
      agents in other traditionally challenging cancers, such as renal cell carcinoma,
      there has been renewed interest in developing novel systemic therapy in HCC. At
      the recent Annual Meeting of the American Society of Clinical Oncology, results
      of a phase 3, randomized, placebo-controlled trial were presented in which
      sorafenib demonstrated improved survival in patients with advanced HCC. This
      landmark study represents the first agent that has demonstrated an improved
      overall survival benefit in this disease and sets the new standard for first-line
      treatment of advanced HCC. For this review, the author concisely summarized the
      current status of molecularly targeted agents that are under clinical development
      in advanced HCC.

PMID- 18041065
TI  - T cell adhesion mechanisms revealed by receptor lateral mobility.
AB  - Cell surface receptors mediate the exchange of information between cells and
      their environment. In the case of adhesion receptors, the spatial distribution
      and molecular associations of the receptors are critical to their function.
      Therefore, understanding the mechanisms regulating the distribution and binding
      associations of these molecules is necessary to understand their functional
      regulation. Experiments characterizing the lateral mobility of adhesion receptors
      have revealed a set of common mechanisms that control receptor function and thus
      cellular behavior. The T cell provides one of the most dynamic examples of
      cellular adhesion. An individual T cell makes innumerable intercellular contacts
      with antigen presenting cells, the vascular endothelium, and many other cell
      types. We review here the mechanisms that regulate T cell adhesion receptor
      lateral mobility as a window into the molecular regulation of these systems, and
      we present a general framework for understanding the principles and mechanisms
      that are likely to be common among these and other cellular adhesion systems. We
      suggest that receptor lateral mobility is regulated via four major mechanisms
      reorganization, recruitment, dispersion, and anchoring-and we review specific
      examples of T cell adhesion receptor systems that utilize one or more of these
      mechanisms.

PMID- 18041066
TI  - Raman spectroscopy can differentiate malignant tumors from normal breast tissue
      and detect early neoplastic changes in a mouse model.
AB  - Raman spectroscopy shows potential in differentiating tumors from normal tissue.
      We used Raman spectroscopy with near-infrared light excitation to study normal
      breast tissue and tumors from 11 mice injected with a cancer cell line. Spectra
      were collected from 17 tumors, 18 samples of adjacent breast tissue and lymph
      nodes, and 17 tissue samples from the contralateral breast and its adjacent lymph
      nodes. Discriminant function analysis was used for classification with principal
      component analysis scores as input data. Tissues were examined by light
      microscopy following formalin fixation and hematoxylin and eosin staining.
      Discriminant function analysis and histology agreed on the diagnosis of all
      contralateral normal, tumor, and mastitis samples, except one tumor which was
      found to be more similar to normal tissue. Normal tissue adjacent to each tumor
      was examined as a separate data group called tumor bed. Scattered morphologically
      suspicious atypical cells not definite for tumor were present in the tumor bed
      samples. Classification of tumor bed tissue showed that some tumor bed tissues
      are diagnostically different from normal, tumor, and mastitis tissue. This may
      reflect malignant molecular alterations prior to morphologic changes, as expected
      in preneoplastic processes. Raman spectroscopy not only distinguishes tumor from
      normal breast tissue, but also detects early neoplastic changes prior to definite
      morphologic alteration.

PMID- 18041067
TI  - Structure-activity relationships in beta-defensin peptides.
AB  - The beta-defensins comprise a large family of small cationic antimicrobial
      peptides widely distributed in plants, mammals and insects. These cysteine rich
      peptides display multifunctional properties with implications as potential
      therapeutic agents. Recent research has highlighted their role in both the innate
      and adaptive immune systems as well as being novel melanocortin ligands. Studies
      investigating structure and function provide an insight into the molecular basis
      of their immunological properties.

PMID- 18041068
TI  - Temporal trends and predictors of perioperative chemotherapy use in elderly
      patients with resected nonsmall cell lung cancer.
AB  - BACKGROUND: The authors assessed patterns of perioperative chemotherapy use in
      elderly patients with resected stage I, II, or IIIA nonsmall cell lung cancer
      (NSCLC) from 1992 to 2002. METHODS: By using data from the Surveillance,
      Epidemiology, and End Results Program, 11,807 patients were identified who had
      resected stage I, II, or IIIA NSCLC between 1992 and 2002 and survived >or=120
      days beyond diagnosis. The rate of perioperative chemotherapy use was measured by
      calendar year, and the association between clinical/demographic characteristics
      and the receipt of chemotherapy was examined by using logistic regression.
      RESULTS: In total, 957 patients with stage I, II, or IIIA NSCLC (8.1% of the
      study population) received perioperative chemotherapy. The proportion of patients
      receiving chemotherapy for stage I NSCLC changed little during the study period.
      Of 3230 patients with stage II and IIIA NSCLC, 609 patients (18.9%) received
      chemotherapy, 423 patients (13%) received chemotherapy combined with radiation.
      452 patients (15.6%) received adjuvant chemotherapy, and 66 patients (2.3%)
      received neoadjuvant chemotherapy. The use of chemotherapy increased
      significantly among patients who were diagnosed after 1994 relative to patients
      who were diagnosed in 1992 after controlling for sociodemographic and treatment
      characteristics (P< .001). There was significantly increased use of new
      generation chemotherapy agents, such as carboplatin and taxanes (P< .001). The
      proportion of patients receiving combined-modality therapy also increased
      significant (P< .001). Younger age, being married, having advanced-stage tumor or
      adenocarcinoma, having a later diagnosis year, receiving radiation, and seeing an
      oncologist were predictors for the receipt of chemotherapy (P< .001).
      CONCLUSIONS: A substantial proportion of Medicare beneficiaries with NSCLC
      received perioperative chemotherapy. Specifically designed prospective trials
      that focus on older patients are needed.

PMID- 18041069
TI  - Colorectal liver metastases contract centripetally with a response to
      chemotherapy: a histomorphologic study.
AB  - BACKGROUND: Recently, there has been considerable interest in neoadjuvant
      chemotherapy for colorectal liver metastases. However, there is little
      information that defines how much liver should be removed after a favorable
      response. METHODS: Liver metastases from 2 groups of patients were analyzed: 25
      metastases were evaluated from a group that did not receive chemotherapy and 26
      lesions were studied from patients who had received systemic chemotherapy before
      resection. All patients except for 1 had 5-fluorouracil (5-FU), leucovorin (LV),
      and irinotecan (CPT-11); 1 had 5-FU and LV alone. The average duration of
      chemotherapy was 2.9+/-0.7 months. Separate assessments of the histopathologic
      features of the central and peripheral portions of each tumor were made. The
      pathologist was blinded to all clinical information. RESULTS: All of the
      untreated metastases had well-circumscribed borders. Irregular borders were seen
      in 6 of the postchemotherapy lesions (26%), which was particularly prominent in
      lesions that had significantly contracted. After chemotherapy, discrete islands
      of viable tumor cells outside of the main tumor mass were seen in 4 patients, but
      all were close to the peripheral margin of the tumor mass. Viable tumor cells
      were more frequent in the periphery of metastases, regardless of chemotherapy
      exposure. Central necrosis was prominent in untreated metastases, but disappeared
      after chemotherapy. In lesions treated with chemotherapy, central fibrosis was
      greater compared with untreated lesions. CONCLUSIONS: After a partial response to
      chemotherapy, liver metastases shrank in a generally concentric fashion. These
      findings support the practice of removing less liver after downsizing with
      chemotherapy.

PMID- 18041070
TI  - A nonrandom association between gastrointestinal stromal tumors and myeloid
      leukemia.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) are KIT-positive mesenchymal
      tumors of the gastrointestinal tract that are driven by activated KIT-signalling
      or platelet-derived growth factor receptor-alpha (PDFGRA) signaling. These tumors
      most commonly occur in the stomach and small intestine and encompass a clinical
      spectrum from benign to malignant. In the current study, the authors examined
      long-term follow-up data of 1892 GIST patients from the U.S. BACKGROUND: Nine
      patients (2 with gastric GISTs and 7 with GISTs of the small intestine) developed
      myeloid leukemia. There were 6 patients (4 women and 2 men) with acute myeloid
      leukemia (AML), including 1 case of promyelocytic and 1 case of myelomonocytic
      leukemia, and 3 patients (2 men and 1 woman) with chronic myeloid leukemia (CML).
      RESULTS: The leukemias developed 1.7 to 21 years after the GIST (median interval,
      6 years). None of the GIST patients had received radiotherapy or chemotherapy
      prior to the leukemia diagnosis. Eight of 9 patients died of leukemia, and none
      died of GIST. All but 1 GIST case was found to have a low mitotic rate (0-1 per
      50 high-power fields); however, tumor size varied from 3 to 18 cm (median, 4.5
      cm). Standardized incidence ratios (SIRs) and their 95% confidence intervals (95%
      CIs) were calculated comparing the incidences of AML/CMLs in GIST patients with
      those in the 2000 through 2003 U.S. population. In GIST patients, the risk of AML
      was found to be significantly higher for women (SIR of 5.14; 95% CI, 1.34-11.4)
      and overall (SIR of 2.96; 95% CI, 1.07-5.8). There was a slightly increased risk
      for CML, but this was not statistically significant (SIR of 3.71; 95% CI, 0.7
      9.1). CONCLUSIONS: Additional epidemiologic, clinical, and pathogenetic studies
      are needed to understand the apparent nonrandom association between GIST and
      myeloid leukemia.

PMID- 18041071
TI  - Poor prognosis in patients with stage I and II oral tongue squamous cell
      carcinoma.
AB  - BACKGROUND: The objective of this study was to compare survival in patients with
      squamous cell carcinoma (SCC) of the oral tongue with that in patients with SCC
      in other oral cavity subsites. METHODS: Patients with stage I and II (T1-T2N0M0)
      SCC of the oral cavity diagnosed between 1988 and 2004 were queried by using the
      Surveillance, Epidemiology, and End Results (SEER) database. The log-rank test
      was used to compare the overall survival (OS) and cause-specific survival (CSS)
      of patients who had oral tongue SCC with those of patients who had SCC of other
      oral cavity subsites. A Cox proportional hazards multivariate analysis was
      performed to evaluate the influence of covariates on the risk of CSS and OS.
      RESULTS: Between 1988 and 2004, 6791 patients with stage I and II SCC of the oral
      cavity were identified. Among them, 40% had oral tongue SCC, and 60% had SCC of
      other oral cavity subsites. The median patient age was 64 years. The 5-year OS
      and CSS rates were 60.9% and 83.5%, respectively, for patients with oral tongue
      SCC versus 64.7% and 94.1%, respectively, for patients with SCC of other oral
      cavity subsites (OS: hazard ratio, 1.24; P< .0001; CSS: hazard ratio, 3.04; P<
      .0001). On multivariate analysis, OS and CSS were influenced significantly by T
      classification, age, sex, and oral tongue subsite. The CSS for patients who had
      stage I and II oral tongue SCC also was unfavorable compared with the CSS for
      stage-matched patients who had SCC of other head and neck sites. CONCLUSIONS:
      Oral tongue SCC was associated with poor survival compared with other oral cavity
      and head and neck sites. These data suggested a potential benefit for
      multimodality therapy in this cohort of patients.

PMID- 18041072
TI  - Using the Edinburgh Postnatal Depression Scale to screen for anxiety disorders.
AB  - Screening for postnatal mood disorders in English-speaking women often uses the
      validated cut-off score of 13 or more on the Edinburgh Postnatal Depression Scale
      (EPDS) to detect probable major depression. Increasingly there is evidence that
      for many women, and men, anxiety disorders can occur postnatally in the absence
      of depression. This study therefore examined data on the three EPDS items
      frequently found to cluster together on an anxiety factor for women (items 3, 4,
      and 5: EPDS-3A), to determine the optimum cut-off score to screen for specified
      anxiety disorders. A sample of 238 women and 218 men were administered a
      diagnostic interview for anxiety and depressive disorders, and completed the
      EPDS, at 6 weeks postpartum. The receiver operating characteristics show that the
      optimum cut-off score on the EPDS-3A for women is 6 or more (possible range: 0
      9), and for men it is 4 or more, though it appears that the factor structure for
      men is different than for women. The conclusion is that the EPDS can be used to
      screen for probable depression in women (using the validated total cut-off score
      of 13 or more) and also probable anxiety (using the EPDS-3A cut-off score of 6 or
      more). For men there is already a validated total cut-off score for both
      depression and anxiety (6 or more)--however, if services are not using this, they
      can use the EPDS-3A score of 4 or more to screen for probable anxiety disorders
      in fathers, though further work needs to be undertaken to clarify whether the
      anxiety factor structure for men is different to that found for women.

PMID- 18041073
TI  - Racial differences in colorectal cancer screening practices and knowledge within
      a low-income population.
AB  - BACKGROUND: Although colorectal cancer (CRC) is the third leading cause of cancer
      death among US women and is particularly deadly among African Americans, CRC
      screening rates remain low. Within a low-income population of women, the authors
      examined racial differences in practices, knowledge, and barriers related to CRC
      screening. METHODS: Face-to-face interviews were conducted with 941 women (white,
      n= 186; African American, n= 755) older than age 50 years who were living in
      subsidized housing communities in 11 cities in North and South Carolina. Women
      were asked questions about their CRC screening history and their knowledge and
      beliefs concerning CRC screening. RESULTS: Half (49%) of the women interviewed
      were within CRC screening guidelines, and this did not vary by race (P= .17).
      However, African American women were half as likely as white women to report
      having had a screening colonoscopy within the past 10 years (odds ratio [OR],
      0.46; P< .001). Awareness of tests for CRC was low overall (39%) and was lower
      among African Americans than whites (OR, 0.44; P< .001). Compared with white
      women, African American women were less likely to report embarrassment as a
      barrier (OR, 0.59; P= .008) and more likely to report lack of insurance coverage
      (OR, 1.75; P= .098). CONCLUSIONS: Efforts must continue to increase women's
      knowledge of both CRC screening tests and colon cancer risk factors. Among these
      low-income women, routine encounters with the healthcare system may present
      opportunities to reduce deficits in CRC knowledge and to improve overall CRC
      screening rates.

PMID- 18041077
TI  - Chronic lung disease in human immunodeficiency virus (HIV) infected children.
AB  - The development of chronic lung disease is common in HIV-infected children. The
      spectrum of chronic HIV-associated lung disease includes lymphocytic interstitial
      pneumonia (LIP), chronic infections, immune reconstitution inflammatory syndrome
      (IRIS), bronchiectasis, malignancies, and interstitial pneumonitis. Chronic lung
      disease may result from recurrent or persistent pneumonia due to bacterial,
      mycobacterial, viral, fungal or mixed infections. In high tuberculosis (TB)
      prevalence areas, M. tuberculosis is an important cause of chronic respiratory
      illness. With increasing availability of highly active antiretroviral therapy
      (HAART) for children in developing countries, a rise in the incidence of IRIS due
      to mycobacterial or other infections is being reported. Diagnosis of chronic lung
      disease is based on chronic symptoms and persistent chest X-ray changes but
      definitive diagnosis can be difficult as clinical and radiological findings may
      be non-specific. Distinguishing LIP from miliary TB remains a difficult challenge
      in HIV-infected children living in high TB prevalence areas. Treatment includes
      therapy for specific infections, pulmonary clearance techniques, corticosteroids
      for children with LIP who are hypoxic or who have airway compression from
      tuberculous nodes and HAART. Children who are taking TB therapy and HAART need
      adjustments in their drug regimes to minimize drug interactions and ensure
      efficacy. Preventative strategies include immunization, chemoprophylaxis, and
      micronutrient supplementation. Early use of HAART may prevent the development of
      chronic lung disease.

PMID- 18041078
TI  - Precursors of cardiorespiratory events in infants detected by home memory
      monitor.
AB  - In 1,079 infants monitored for >700,000 hr at home for apnea or bradycardia, we
      found an association between infants having multiple events exceeding
      conventional or a priori defined more extreme thresholds and less favorable
      developmental outcome at 1 year of age than infants with few or no events. If it
      is necessary to prevent such events to minimize risk for developmental morbidity,
      there is reason to determine whether there are disturbances in advance of the
      apnea or bradycardia that herald their onset. In the 85 infants with at least 1
      extreme event and 1 conventional event, we hypothesized that apnea and
      bradycardia do not occur de novo but rather are preceded by cardiorespiratory and
      hemoglobin O2 saturation changes. We compared recorded time intervals preceding
      these events, and we analyzed three preceding time intervals for each
      conventional and extreme event, and each non-event recording: Time-2 hr: up to 2
      hr before; Time-1 hr: up to 1 hr before; and Time-75 sec: the 75 sec immediately
      preceding each event. O2 saturation progressively decreased preceding both
      conventional and extreme events, and progressive increases occurred in heart and
      breathing rate variability. Duration of respiratory pauses and of periodic
      breathing progressively increased preceding conventional events, respiratory rate
      variability increased immediately preceding conventional events and at 1 hr
      preceding extreme events, and O2 saturation decreased immediately preceding both
      conventional and extreme events. Thus, conventional and extreme events do not
      occur de novo but rather are preceded by autonomic instability of the
      cardiorespiratory system.

PMID- 18041079
TI  - Ventilation induced pneumothorax following resolved empyema.
AB  - We report a case of pneumothorax as a result of positive pressure ventilation in
      a child previously treated for empyema. Three months following discharge for
      successful treatment of empyema our patient received a general anesthetic for an
      elective MRI of the brain for investigation of nystagmus. During recovery from
      the anesthetic he developed respiratory distress and was found to have a
      loculated pneumothorax. We propose that pleural fragility in childhood empyema
      possibly persists even after clinical resolution and in this case for up to 3
      months. The complication of pneumothorax should be considered in all patients
      receiving positive pressure ventilation following resolved empyema.

PMID- 18041080
TI  - Airway epithelial cell signaling in response to bacterial pathogens.
AB  - The airway epithelium represents a primary site for the introduction and
      deposition of potentially pathogenic microorganisms into the body, through
      inspired air. The epithelial mucosa is an important component of the innate
      immune system that recognizes conserved structures in microorganisms and
      initiates appropriate signaling to recruit and activate phagocytic cells to the
      airways. This review focuses on how airway epithelial cells sense and respond to
      the presence of bacterial pathogens. The major signaling cascades initiated by
      epithelial receptors that lead to phagocyte recruitment to the airways as well as
      the ability of the epithelium to regulate inflammation are discussed.

PMID- 18041081
TI  - A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic
      fibrosis and Pseudomonas aeruginosa infection.
AB  - BACKGROUND: Aztreonam lysine for inhalation (AZLI) is being developed for
      treatment of CF patients with Pseudomonas aeruginosa airway infection. METHODS:
      This double-blind, randomized, placebo-controlled Phase 2 study evaluated the
      safety, tolerability and efficacy of 75 and 225 mg AZLI administered BID for 14
      days using the eFlow Electronic Nebulizer (Pari Innovative Manufacturers, Inc.,
      Midlothian, VA). Patients were 13 years and older with FEV1>or=40% predicted,
      chronic P. aeruginosa infection, and had used no anti-pseudomonal antibiotics for
      56 days. RESULTS: Of 131 patients screened, 105 received AZLI or placebo. Mean
      age was 26 years and mean FEV1 percent predicted was 77% at baseline. There was a
      statistically significant reduction, compared to placebo, in P. aeruginosa CFU
      density in each AZLI group at Days 7 and 14 (P<0.001). The planned primary
      analysis, percent change in FEV1 at Day 14, demonstrated no statistically
      significant difference. Post hoc analysis demonstrated significant increase in
      FEV1 at Day 7 for the subset of patients with baseline FEV1<75% predicted in the
      225 mg AZLI group. Bronchodilator use was associated with greater improvement in
      FEV1, as well as greater reduction in P. aeruginosa bacterial density and higher
      plasma aztreonam concentrations in the 225 mg AZLI group. Adverse events were
      similar between placebo and AZLI although there was a trend toward increased
      respiratory symptoms in the 225 mg AZLI group. CONCLUSION: These data support the
      further development of AZLI and provide information for the design of subsequent
      studies.

PMID- 18041082
TI  - Mycoplasma pneumonia and pulmonary embolism in a child due to acquired
      prothrombotic factors.
AB  - We report on a child with Mycoplasma pneumonia, who developed an unexplained new
      oxygen requirement. He was found to have an ileo-femoral thrombosis and an acute
      pulmonary embolus, with positive anti-phospholipid antibodies and acquired
      activated protein C resistance. These are both acquired risk factors for venous
      thrombosis. He was successfully anti-coagulated and well at follow-up with
      disappearance of the anti-phospholipid antibodies, and normalization of his
      activated protein C activity. Children who present with Mycoplasma infections who
      run an atypical course should be monitored closely for signs of thrombosis.
      Thrombosis formation should also be considered in those children with
      deteriorating respiratory status, but little change in radiographical findings.
      Children found to have developed thrombi should be investigated with a full
      thrombophilia screen to elicit both congenital and acquired risk factors, and
      should be anti-coagulated appropriately.

PMID- 18041083
TI  - Lung resection in cystic fibrosis: a survival analysis.
AB  - Lung resection may be considered for cystic fibrosis (CF) patients showing
      localized severe chronic atelectasis and/or bronchiectasis. Nonetheless,
      literature on survival after surgery is scarce. This study was carried out to
      assess survival time after partial lung resection. Twenty-one CF patients were
      operated from 1988 to 2003 and were followed until November 30th, 2004. Survival
      analysis was performed through Kaplan-Meier method. Mean age at resection was
      8.09 years (SD 4.40 years) and two-thirds were females. Z-scores for height,
      weight, and body mass index as well as FEV1 values showed no statistical
      significance when comparing values obtained from 2 years before to 2 years after
      resection. Eleven years after resection, survival probability was 93.8%. Our
      results suggest that lobectomy or segmentectomy are safe procedures and should be
      considered in carefully selected patients with unilateral severe symptomatic
      localized and chronic persistent atelectasis and/or bronchiectasis refractory to
      conservative management.

PMID- 18041087
TI  - Primary central nervous system vasculitis: progress and questions.

PMID- 18041088
TI  - Transient epileptic amnesia: a new epileptic syndrome in development?

PMID- 18041089
TI  - The peroxisome proliferator-activated receptor-gamma agonist 1,1-bis(3'-indolyl)
      1-(p-trifluoromethylphenyl)methane suppresses manganese-induced production of
      nitric oxide in astrocytes and inhibits apoptosis in cocultured PC12 cells.
AB  - Reactive astrogliosis is a prominent neuropathologic feature of manganism, a
      neurodegenerative disorder caused by excessive accumulation of manganese (Mn) in
      the basal ganglia. Activation of astrocytes has been linked to neuronal injury in
      manganism resulting from overproduction of inflammatory mediators, including
      tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFNgamma), interleukin
      1beta (IL-1beta), and nitric oxide (NO), but the signaling mechanisms by which Mn
      regulates these factors remain poorly understood. We previously reported that Mn
      enhances production of NO in activated astrocytes that promotes apoptosis in
      cocultured neuronal cells by a mechanism involving the transcription factor
      nuclear factor-kappaB (NF-kappaB) (Liu et al., 2005). Because NF-kappaB-dependent
      expression of inducible nitric oxide synthase (NOS2) can be antagonized by the
      nuclear orphan receptor peroxisome proliferator-activated receptor-gamma
      (PPARgamma), we postulated that a novel agonist of this receptor, 1,1-bis(3'
      indolyl)-1-(p-trifluoromethylphenyl)methane (cDIM1), would suppress expression of
      NOS2 in astrocytes and protect cocultured neuronal cells from apoptosis.
      Submicromolar concentrations of cDIM1 potently suppressed production of NO and
      expression of NOS2 in cultured astrocytes exposed to Mn and IFNgamma/TNFalpha and
      prevented apoptosis in cocultures of differentiated PC12 cells, but this
      neuroprotective effect was lost in the absence of astrocytes. By using
      fluorescence reporter and chromatin immunoprecipitation (ChIP) assays, we found
      that cDIM1 prevented activation of NF-kappaB in astrocytes by a mechanism
      involving stabilization of the nuclear corepressor 2 (NCoR2) on the proximal NF
      kappaB binding site of the NOS2 promoter. These data suggest that PPARgamma may
      be an effective target for limiting inflammatory activation of astrocytes during
      neurologic injury.

PMID- 18041091
TI  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionate attenuates glutamate
      induced caspase-3 cleavage via regulation of glycogen synthase kinase 3beta.
AB  - Preconditioning of sublethal ischemia exhibits neuroprotection against subsequent
      ischemia-induced neuronal death. It has been indicated that glutamate, an
      excitatory amino acid, is involved in the pathogenesis of ischemia-induced
      neuronal death or neurodegeneration. To elucidate whether prestimulation of
      glutamate receptor could counter ischemia-induced neuronal death or
      neurodegeneration, we examined the effect of alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionate (AMPA), an ionotropic subtype of glutamate receptor, on
      excess glutamate-induced excitotoxicity using primary cortical neuronal cultures.
      We found that AMPA exerted a neuroprotective effect in a time- and concentration
      dependent manner. A blocker of phosphatidylinositol-3 kinase (PI3K), LY294002 (10
      microM), significantly attenuated AMPA-induced protection. In addition, Ser473 of
      Akt/PKB, a downstream target of PI3K, was phosphorylated by AMPA administration
      (10 microM). Glycogen synthase kinase 3beta (GSK3beta), which has been reported
      to be inactivated by Akt, was phosphorylated at Ser9 by AMPA. Ser9-phosphorylated
      GSK3beta or inactivated form would be a key molecule for neuroprotection, insofar
      as lithium chloride (100 microM) and SB216763 (10 microM), inhibitors of
      GSK3beta, also induced phosphorylation of GSK3beta at Ser9 and exerted
      neuroprotection, respectively. Glutamate (100 microM) increased cleaved caspase
      3, an apoptosis-related cysteine protease, and caspase-3 inhibitor (Ac-DEVD-CHO;
      1 microM) blocked glutamate-induced excitotoxicity in our culture. AMPA (10
      microM, 24 hr) and SB216763 (10 microM) prominently decreased glutamate-induced
      caspase-3 cleavage. These findings suggest that AMPA activates PI3K-Akt and
      subsequently inhibits GSK3beta and that inactivated GSK3beta attenuates glutamate
      induced caspase-3 cleavage and neurotoxicity.

PMID- 18041092
TI  - Gene expression and protein localization of calmodulin-dependent
      phosphodiesterase during ontogenesis of chick retina.
AB  - Calmodulin-dependent phosphodiesterase (PDE1) is a key enzyme in cyclic
      nucleotides metabolism. We studied its gene expression and protein localization
      during retinal development in chick embryos. Western blot and densitometric
      analysis demonstrated that the expression of the three isoforms changed during
      development. PDE1A was highly expressed at the early stages and decreased as
      development proceeded. PDE1B expression remained relatively low and constant over
      time. PDE1C showed a prominent increase (13-fold) between embryonic day (E) 7 and
      E13, followed by a moderate increase between E13 and postnatal day (P) 1. The
      presence of the enzyme in the different retinal locations was strongly modulated
      by development. PDE1A immunostaining was first detected at the ganglion cell
      level (E7), then in the outer retina (E15-E21). At P5, the immunostaining was
      confined in the optic fiber layer. Isoform C immunolocalization followed the same
      inner-outer pattern as isoform A. At 5 days posthatching (P5), the
      immunoreactivity was restricted, as well as for the isoform A, in the optic fiber
      layer. The isoform B immunolabelling was low and evenly distributed across the
      retina at all stages. The different developmental profiles of PDE1A, PDE1B, and
      PDE1C induced a temporal modulation in cyclic nucleotides concentration,
      suggesting specific roles of this enzyme in the morphofunctional development of
      retinal circuitry.

PMID- 18041090
TI  - Mitochondrial nuclear receptors and transcription factors: who's minding the
      cell?
AB  - Mitochondria are power organelles generating biochemical energy, ATP, in the
      cell. Mitochondria play a variety of roles, including integrating extracellular
      signals and executing critical intracellular events, such as neuronal cell
      survival and death. Increasing evidence suggests that a cross-talk mechanism
      between mitochondria and the nucleus is closely related to neuronal function and
      activity. Nuclear receptors (estrogen receptors, thyroid (T3) hormone receptor,
      peroxisome proliferators-activated receptor gamma2) and transcription factors
      (cAMP response binding protein, p53) have been found to target mitochondria and
      exert prosurvival and prodeath pathways. In this context, the regulation of
      mitochondrial function via the translocation of nuclear receptors and
      transcription factors may underlie some of the mechanisms involved in neuronal
      survival and death. Understanding the function of nuclear receptors and
      transcription factors in the mitochondria may provide important pharmacological
      utility in the treatment of neurodegenerative conditions. Thus, the modulation of
      signaling pathways via mitochondria-targeting nuclear receptors and transcription
      factors is rapidly emerging as a novel therapeutic target.

PMID- 18041094
TI  - Early auditory deprivation alters expression of NMDA receptor subunit NR1 mRNA in
      the rat auditory cortex.
AB  - The expression of NMDA receptor NR1 subunit mRNA was studied in rat auditory
      cortex (AC) on different postnatal days using digoxigenin-labeled oligonucleotide
      probes. The results showed that NR1 expression increased from birth to postnatal
      day 35 (P35) and remained constant until P56. The most significant increases
      occurred between P7 and P14. Changes in NR1 mRNA expression in rats subjected to
      monaural hearing deprivation on P7, P21, P35, and P49 were examined on P56.
      Between P7 and P21, when the rat auditory system was still in a critical period
      of development, NR1 mRNA expression was lower in the contralateral AC, which
      received auditory signals from the plugged ear, than in the ipsilateral AC.
      However, no significant difference was observed between the rats deprived of
      hearing on P35 and those deprived of hearing on P42, the end of the critical
      period of auditory development. These results showed that monaural hearing
      deprivation during early postnatal development was associated with decreased NR1
      mRNA expression in the contralateral AC and suggested the involvement of NR1 in
      auditory function during development. They also indicated that, during postnatal
      development, environmental factors changed the functional plasticity of neurons
      in the AC through NR1 receptor expression. Taken together, these findings provide
      a possible underlying mechanism for the development of postnatal auditory
      function.

PMID- 18041095
TI  - Effect of growth factors and steroids on transglutaminase activity and expression
      in primary astroglial cell cultures.
AB  - Type-2 transglutaminase (TG-2) is a multifunctional enzyme involved in the
      regulation of cell differentiation and survival that recently has been shown to
      play an emerging role in astrocytes, where it is involved in both proliferation
      and differentiation processes. Growth factors (GFs) such as EGF, basic fibroblast
      growth factor, insulin-like growth factor-I (IGF-I), and insulin (INS) are
      trophic and mitogenic peptides that participate in neuron-glia interactions and
      stimulate neuronal and astroglial proliferation and differentiation. Steroid
      hormones such as glucocorticoids and estrogens also play a pivotal role in
      neuronal and astroglial proliferation and differentiation and are key hormones in
      neurodegenerative and neuroprotective processes. We investigated the effects of
      the interaction of GFs with dexamethasone (DEX) or 17beta-estradiol (E(2)) on TG
      2 activity and their expression in cultured astrocytes. We observed a significant
      increase in TG-2 activity and expression in astroglial cells treated for 24 hr
      with IGF-I, EGF, or INS. Priming of the cells with DEX or E(2), for 48 hr also
      led to an increase in TG-2 levels. When growth factors were present in the last
      24 hr of the steroid treatment, a reduction in TG-2 expression and activity and a
      different subcellular TG-2 distribution were found. Our data indicate that
      steroid hormone-GF interaction may play an important role in astroglial function.
      The effect on TG-2 could be part of the regulation of intracellular pathways
      associated with the astrocyte response observed in physiological conditions and,
      possibly, also in neuropathological diseases.

PMID- 18041093
TI  - Glial ensheathment of peripheral axons in Drosophila.
AB  - The ensheathment of neurons and their axons creates an ion-sensitive
      microenvironment that allows rapid conduction of nerve impulses. One of the
      fundamental questions about axonal ensheathment is how insulating glial cells
      wrap around axons. The mechanisms that underlie insulation of axons in
      invertebrates and vertebrates are not fully understood. In the present article we
      address cellular aspects of axonal ensheathment in Drosophila by taking advantage
      of glial mutants that illustrate a range of phenotypic defects including
      ensheathment of axons. From the findings of these mutant studies, we summarize
      that loss of glial cells, defects in glial membrane wrapping, failure of glial
      migration, and loss of specialized ladderlike septate junctions between
      ensheathing glial membranes result in axon-glial functional defects. These
      studies provide a broad perspective on glial ensheathment of axons in Drosophila
      and key insights into the anatomical and cellular aspects of axonal insulation.
      Given the powerful genetic approaches available in Drosophila, the axonal
      ensheathment process can be dissected in great detail to reveal the fundamental
      principles of ensheathment. These observations will be relevant to understanding
      the very similar processes in vertebrates, where defects in glial cell functions
      lead to devastating neurological diseases.

PMID- 18041101
TI  - A panel of multiple markers associated with chronic systemic inflammation and the
      risk of atherogenesis is detectable in asthma and chronic obstructive pulmonary
      disease.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are both lung diseases
      involving chronic inflammation of the airway. The injury is reversible in asthma
      whereas it is mostly irreversible in COPD. Both patients of asthma and COPD are
      known at risk for cardiovascular disease (CVD) and type 2 diabetes (T2DM),
      nephropathy, and cancer. We measured multiple risk markers for atherogenesis in
      55 patients with asthma and 62 patients with COPD. We wanted to know whether risk
      markers for atherogenesis corresponding to sequence of events of chronic
      inflammation were also detectable in the airway inflammatory diseases. Elevation
      of almost all markers involving inflammation of the endothelial cells in the
      coronary artery were detectable in asthma and COPD involving the inflammation of
      the epithelial cell lining of the airway. Both the level and % elevation of all
      markers were found mostly higher in COPD, the more severe form of the lung
      disease. We believe that these markers are useful for predicting risk of
      developing clinical complications such as CVD.

PMID- 18041102
TI  - Chronic pain and depression among geriatric psychiatry inpatients.
AB  - OBJECTIVES: We examined whether chronic pain among depressed geriatric inpatients
      was associated with several clinical variables-comorbid psychiatric and medical
      diagnoses, length of hospitalization, suicidal ideation, and sleep duration.
      METHODS: Medical charts of inpatients admitted to a geriatric psychiatry unit
      over 2 years were examined retrospectively; 148 patients with a depressive
      disorder were identified. Admission pain assessments were used to classify
      whether patients had chronic pain. Other variables of interest were collected
      from charts. RESULTS: 62% of patients reported chronic pain. In multivariate
      regression analysis, depressed older adults with chronic pain were more likely to
      report suicidal ideation, be diagnosed with personality disorder, have higher
      medical burden, and experience decreased total sleep time compared to depressed
      older adults without chronic pain. CONCLUSIONS: Chronic pain--common in depressed
      older adults--may influence clinical features of depression and should be
      assessed as a possible suicide risk factor. Prospective studies should examine
      causal relationships and determine the effects of adequate pain treatment on
      depression course and suicide risk in older adults.

PMID- 18041103
TI  - Recombinant therapeutic proteins: production platforms and challenges.
AB  - Since the approval of insulin in 1982, more than 120 recombinant drug substances
      have been approved and become available as extremely valuable therapeutic
      options. Exact copying of the most common human form is no longer a value per se,
      as challenges, primarily related to the pharmacokinetics of artificial
      recombinant drugs, can be overcome by diverging from the original. However,
      relatively minor changes in manufacturing or packaging may impact safety of
      therapeutic proteins. A major achievement is the development of recombinant
      proteins capable of entering a cell. Such drugs open up completely new
      opportunities by targeting intracellular mechanisms or by substituting
      intracellularly operating enzymes. Concerns that protein variants would cause an
      intolerable immune response turned out to be exaggerated. Although most
      recombinant drugs provoke some immune response, they are still well tolerated.
      This knowledge might result in a change in attitude towards antibody formation,
      i.e., neutralizing antibody activity (in vitro) may be overcome by dosing
      consistently on the basis of antibody titers and not only on body weight. As with
      other drugs, efficacy and safety of therapeutic proteins have to be demonstrated
      in clinical studies, and superiority over available products has to be proven
      instead of just claimed.

PMID- 18041104
TI  - Studies of diabetes, thiazolidinediones, and coronary heart disease.

PMID- 18041105
TI  - Is there a connection between methylphenidate and cancer in youth?

PMID- 18041106
TI  - Methylphenidate use in children and risk of cancer at 18 sites: results of
      surveillance analyses.
AB  - PURPOSE: A recent report linked methylphenidate (MPH) use in children to
      cytologic abnormalities in plasma lymphocytes, a possible cancer biomarker. The
      purpose of this study was to investigate the association of MPH use and childhood
      cancer risk. METHODS: Using automated pharmacy databases and the SEER-affiliated
      cancer registry of the Kaiser Permanente Medical Care Program (KPMCP), we
      compared cancer rates at 18 sites among 35,400 MPH users who received it before
      age 20 to rates among KPMCP membership (age, sex, and calendar year
      standardized). Medical records of MPH exposed cancer cases were reviewed to
      identify the presence of established risk factors. RESULTS: There were 23 cancers
      among MPH users, versus 20.4 expected (standardized morbidity ratio, SMR = 1.13,
      95% confidence interval (0.72, 1.70)). Given the small number of cancers, site
      specific SMR estimates were imprecise. Only one SMR was statistically significant
      at the p < 0.05 level, which given the number of comparisons is consistent with
      the absence of a true association at any site. MPH use was associated with
      increased risk of lymphocytic leukemia (SMR = 2.64 (1.14, 5.20)), based on eight
      observed cases). The medical records of these exposed cases did not reveal any
      lymphocytic leukemia risk factors (prior cancer, radiotherapy or chemotherapy, or
      Down syndrome). CONCLUSIONS: Our results are consistent with no moderate or
      strong association between MPH use and cancer risk in children, although our
      ability to examine dose and duration of use or risk at specific sites was limited
      by small numbers. Further study of MPH use and lymphocytic leukemia risk is
      needed to determine whether our results are due to chance alone.

PMID- 18041108
TI  - A nanoparticulate drug-delivery system for rivastigmine: physico-chemical and in
      vitro biological characterization.
AB  - The preparation and characterization of surface-PEGylated polymeric nanoparticles
      are described. These systems were obtained by UV irradiation of PHM and PHM
      PEG(2000) as an inverse microemulsion, using an aqueous solution of the PHM/PHM
      PEG(2000) copolymer mixture as the internal phase and triacetin saturated with
      water as the external phase, and characterized by dimensional analysis, zeta
      potential measurements and XPS. in vitro biological tests demonstrated their cell
      compatibility and their ability to escape from phagocytosis. Rivastigmine was
      encapsulated into the nanoparticle structure and drug-release profiles from
      loaded samples were investigated in PBS at pH = 7.4 and human plasma.

PMID- 18041109
TI  - Impact of rapid molecular screening for meticillin-resistant Staphylococcus
      aureus in surgical wards.
AB  - BACKGROUND: This study aimed to establish the feasibility and cost-effectiveness
      of rapid molecular screening for hospital-acquired meticillin-resistant
      Staphylococcus aureus (MRSA) in surgical patients within a teaching hospital.
      METHODS: In 2006, nasal swabs were obtained before surgery from all patients
      undergoing elective and emergency procedures, and screened for MRSA using a rapid
      molecular technique. MRSA-positive patients were started on suppression therapy
      of mupirocin nasal ointment (2 per cent) and undiluted chlorhexidine gluconate
      bodywash. RESULTS: A total of 18,810 samples were processed, of which 850 (4.5
      per cent) were MRSA positive. In comparison to the annual mean for the preceding
      6 years, MRSA bacteraemia fell by 38.5 per cent (P < 0.001), and MRSA wound
      isolates fell by 12.7 per cent (P = 0.031). The reduction in MRSA bacteraemia and
      wound infection was equivalent to a saving of 3.78 beds per year (276,220 pounds
      sterling), compared with the annual mean for the preceding 6 years. The cost of
      screening was 302,500 pounds sterling, making a net loss of 26,280 pounds
      sterling. Compared with 2005, however, there was a net saving of 545,486 pounds
      sterling. CONCLUSION: Rapid MRSA screening of all surgical admissions resulted in
      a significant reduction in staphylococcal bacteraemia during the screening
      period, although a causal link cannot be established.

PMID- 18041110
TI  - Ca2+ responses to thyrotropin-releasing hormone and angiotensin II: the role of
      plasma membrane integrity and effect of G11alpha protein overexpression on
      homologous and heterologous desensitization.
AB  - The molecular mechanisms involved in GPCR-initiated signaling cascades where the
      two receptors share the same signaling cascade, such as thyrotropin-releasing
      hormone (TRH) and angiotensin II (ANG II), are still far from being understood.
      Here, we analyzed hormone-induced Ca(2+) responses and the process of
      desensitization in HEK-293 cells, which express endogenous ANG II receptors.
      These cells were transfected to express exogenously high levels of TRH receptors
      (clone E2) or both TRH receptors and G(11)alpha protein (clone E2M11). We
      observed that the characteristics of the Ca(2+) response, as well as the process
      of desensitization, were both strongly dependent on receptor number and
      G(11)alpha protein level. Whereas treatment of E2 cells with TRH or ANG II led to
      significant desensitization of the Ca(2+) response to subsequent addition of
      either hormone, the response was not desensitized in E2M11 cells expressing high
      levels of G(11)alpha. In addition, stimulation of both cell lines with THR
      elicited a clear heterologous desensitization to subsequent stimulation with ANG
      II. On the other hand, ANG II did not affect a subsequent response to TRH. ANG II
      mediated signal transduction was strongly dependent on plasma membrane integrity
      modified by cholesterol depletion, but signaling through TRH receptors was
      altered only slightly under these conditions. It may be concluded that the level
      of expression of G-protein-coupled receptors and their cognate G-proteins
      strongly influences not only the magnitude of the Ca(2+) response but also the
      process of desensitization and resistance to subsequent hormone addition.

PMID- 18041112
TI  - Experts call for reform of the International Monetary Fund.

PMID- 18041111
TI  - Retraction notice to "the effect of dental overbite on eustachian tube
      dysfunction in Iranian children" [Int J Pediatr Otorhinolaryngol 2007; 71: 325
      31].

PMID- 18041113
TI  - Retraction notice to "gC1qR expression in chimpanzees with resolved and chronic
      infection: potential role of HCV core/gC1qR-mediated T cell suppression in the
      outcome of HCV infection" [Virology 346 (2006) 324-327].

PMID- 18041114
TI  - Radiographers' role in radiological reporting.

PMID- 18041115
TI  - Towards the appropriate use of diagnostic imaging.

PMID- 18041116
TI  - Human embryonic stem cells leap the barrier.

PMID- 18041117
TI  - [Recommendation for the prevention of nosocomial infections in neonatal intensive
      care patients with a birth weight less than 1,500 g. Report by the Committee of
      Hospital Hygiene and Infection Prevention of the Robert Koch Institute].

PMID- 18041118
TI  - Studies with vitamin E and beta-carotene as single agents do not prove lack of
      benefit.

PMID- 18041119
TI  - Antenatal care implications of population-based trends in Down syndrome birth
      rates.

PMID- 18041120
TI  - Current awareness in prenatal diagnosis.
AB  - In order to keep subscribers up-to-date with the latest developments in their
      field, John Wiley & Sons are providing a current awareness service in each issue
      of the journal. The bibliography contains newly published material in the field
      of prenatal diagnosis. Each bibliography is divided into 17 sections: 1 Reviews;
      2 General Interest; 3 Normal Fetal Development; 4 Gametogenesis and Pre
      implantation Diagnosis; 5 First Trimester Diagnosis; 6 Second Trimester
      Diagnosis; 7 Fetal Diagnosis by Ultrasound and Other Imaging; 8 Maternal
      Screening; 9 Screening for Carriers of Genetic Abnormality; 10 Technological
      Developments; 11 Confined Placental Mosaicism and Uniparental Disomy; 12
      Molecular Cytogenetics; 13 Fetal Cells in Maternal Circulation; 14 Fetal Therapy;
      15 Psychosocial Aspects; 16 Epidemiology and Environmental Factors; 17
      Developmental Pathology. Within each section, articles are listed in alphabetical
      order with respect to author. If, in the preceding period, no publications are
      located relevant to any one of these headings, that section will be omitted.

PMID- 18041121
TI  - [Molecular-biologic analysis of avian influenza virus isolates which caused
      epizootics on the south of West Siberia and in Crimea].
AB  - The objective of the study was to determine reasons of poultry deaths in Crimea
      Republic in December 2005 as well as isolation, identification, and comparative
      analysis of pathogens, which caused epizootics in Siberia and Crimea. During
      epizootic in poultry in North-East Crimea highly pathogenic avian influenza virus
      H5N1 was isolated. Phylogenetic analysis of RNA sequences revealed that they
      belong to one big cluster. Isolated strain was close to viruses, which caused
      epizootic in July-August 2005 in the south of West Siberia. Conclusion about the
      high importance of the south of West Siberia in spreading of highly pathogenic
      influenza viruses H5N1 in Eurasia was made.

PMID- 18041122
TI  - [Influence of probiotic enterococci on the growth of Streptococcus agalactiae].
AB  - Individual features of sensitivity of some strains of group B streptococci (GBS)
      to influence of 2 probiotic cultures of Enterococcus faecium (SF68 and L3) have
      been studied by double agar test. E. faecium L3 strain had higher antagonistic
      activity to GBS. Two genes encoding enterocins A and B as well as genes
      responsible for the expression of the former two genes were found in the genome
      of this strain. The supernatant and peptide extract of E. faecium L3 contained
      thermostable low molecular weight peptides which inhibited growth of listeria and
      GBS but at lesser extent compared with native enterococci. Obtained data allow to
      suggest that antagonistic activity of enterococci against GBS may be affiliated
      with production of enterocins A and B and can be increased by the presence of
      other metabolites.

PMID- 18041123
TI  - [Influence of doxorubicin on the development of resistance of staphylococci to
      ceftriaxone].
AB  - Effect of combined use of doxorubicin and ceftriaxone on 5 strains of
      Staphylococcus aureus (standard S. aureus ATCC 29213 and 4 isolated strains) was
      studied. The method of passages in meat-pepton broth with constant and increasing
      concentrations of ceftriaxone in presence of 1/2 and 1/4 minimum inhibitory
      concentration of doxorubicin was used. It has been shown that doxorubicin in such
      concentrations does not influence on the development of resistance of tested
      strains to ceftriaxone. The combination of doxorubicin as anti-tumor drug with
      intercalary action and ceftriaxone does not increase the risk of development of
      resistance of staphylococci to antibiotics, which has a matter during their
      combined use.

PMID- 18041124
TI  - [Etiology of nosocomial surgical infections caused by gram-negative bacteria, and
      profile of their antibiotic resistance].
AB  - Microbiological monitoring of microbial landscape of gram-negative bacteria-
      etiological agents of nosocomial surgical infections--was performed as well as
      their level of antibiotic resistance was studied. Two hundred forty-four strains
      were isolated. Antimicrobial susceptibility was assessed by the method of serial
      microdilutions. Spectrum of Gram-negative microorganisms was represented by 3
      groups: fermenting (62.7%), nonfermenting (34.8%), and nonidentified microbes
      (2.5%). Spectrum of gram-negative etiological agents of nosocomial surgical
      infections was represented mainly by Pseudomonas aeruginosa, Acinetobacter
      baumanii, Escherichia coli, and Klebsiella. Most active antibacterial drugs
      against studied strains were carbapenems (imipenem and meropenem).

PMID- 18041125
TI  - [Direct nitrate reductase method of assessment of Mycobacterium tuberculosis
      susceptibility to drug].
AB  - Microbiological method of direct accelerated assessment of resistance of
      Mycobacterium tuberculosis to rifampicin and isoniazide was developed which is
      able to detect multidrug resistant M. tuberculosis 10-21 days after obtaining of
      sputum--4-5 times faster compared with the method of absolute concentrations.
      Efficacy of the method was 0.93 and 0.96 during assessment of susceptibility to
      rifampicin and isoniazide respectively.

PMID- 18041126
TI  - [Role of heat shock proteins in developing of innate immunity reactions].
AB  - Increasing interest to heat shock proteins (HSP) from biologists and medics is
      connected to widespread distribution of HSP in live nature and reflects their key
      role in support of life functions which is based on the unique polyfunctionality
      of these biomolecules. Together with main function, which is defense of biologic
      systems from stress effects, some HSP in the process of evolution acquired the
      ability to incorporate in the reactions of the immune system. The in vestmen of
      this protein in practical reactions of innate immunity system are described.
      Analysis of mechanisms underlying the adjuvant effect of pro- and eukaryotic HSP
      in innate immunity system is presented. HSP receptor structures on target cells
      as well as triggered intracellular signaling pathways are described.

PMID- 18041127
TI  - [Staphylococcal toxin of toxic shock syndrome].
AB  - Literature data on toxic shock syndrome staphylococcal toxin (TSST-1) are
      summarized; properties of Staphylococcus aureus strains producing TSST-1,
      nutrient media, and factors influencing on production of TSST-1 are reviewed.
      Physical and chemical properties of the toxin, its molecular characteristics,
      genetic regulation of its production, mechanism of action, and diseases which it
      causes are also discussed. Clinical and histologic signs of toxic shock syndrome
      (TSS), its diagnostic criteria, susceptibility of people to TSS, antigenic and
      serologic properties of the toxin, epidemiology of the infection caused by TSST-1
      producing strains of staphylococci, methods of TSST-1 extraction and
      identification are described.

PMID- 18041128
TI  - [Study of the spread of aggressive behavior in patients with new-onset pulmonary
      tuberculosis].
AB  - Wearisome mental stress arising from experiencing aggressive sensations in the
      subjectively and objectively unbearable situation may be a significant
      contributor to the development of a psychosomatic disorder. A hundred and twenty
      patients with new-onset pulmonary tuberculosis underwent a psychological study.
      The steady-state personality trait in these patients is hostility as
      overpretentiousness, susceptibility to offence, and suspiciousness. The
      development of hostility in patients with pulmonary tuberculosis is associated
      with masterful upbringing in their parental families, which promotes the
      development of a sense of guilt, sensitivity to their criticism, restrained
      actions, and inattention. The inclination of these patients to feel themselves
      attacked victims forces them to mobilize their energy to repulse the aggressive
      reality as they perceive, maintaining the abnormally high level of affective
      tension that impairs autonomic balance in the body and makes the treatment of
      tuberculosis ineffective. It is expedient to take into account the revealed
      psychological characteristics of patients with pulmonary tuberculosis in the
      mentally corrective constituent of a therapeutic process in order to achieve the
      optimal cooperation in the physician-patient-family system.

PMID- 18041129
TI  - [Pulmonary function in patients with disseminated pulmonary tuberculosis].
AB  - Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1
      second (FEV1), FEV1/VC%, PEF, MEF25%, MEF50%, MEF75%, TLS, TGV, pulmonary
      residual volume (PRV), Raw, Rin, Rex, DLCO-SB, DLCO-SS, PaO2, and PaCO2 were
      determined in 29 patients with disseminated pulmonary tuberculosis. Pulmonary
      dysfunction was detected in 93.1% of the patients. Changes were found in lung
      volumes and capacities in 65.5%, impaired bronchial patency and pulmonary gas
      exchange dysfunction were in 79.3 and 37.9%, respectively. The changes in
      pulmonary volumes and capacities appeared as increased PRV, decreased VC, FVC,
      and TLS, decreased and increased TGV; impaired bronchial patency presented as
      decreased PEF, MEF25%, MEF50%, MEF75%, and FEV1/VC% and increased Raw, Rin, and
      Rex; pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SS and
      PaO2 and decreased and increased PaCO2. The observed functional changes varied
      from slight to significant and pronounced with a preponderance of small
      disorders, a lower detection rate of significant disorders, and rare detection of
      very pronounced ones.

PMID- 18041130
TI  - [Ordinal scales for quantification of x-ray and clinical manifestations of
      infiltrative pulmonary tuberculosis].
AB  - Ordinal scales for quantification of X-ray and clinical manifestations of
      infiltrative pulmonary tuberculosis are proposed. Correlation analysis was made
      to compare the values of the proposed ordinal scales with the
      clinicohematological and clinicoimmunological parameters of a systemic reaction
      to inflammation, as well as with admission body temperature and the blood levels
      of lipid peroxidation products. The findings suggest the adequate validity of the
      proposed scales for practical application.

PMID- 18041131
TI  - [Complex of repair DNA polymerase beta with autonomous 3'-->5'-exonuclease shows
      increased accuracy of DNA synthesis].
AB  - The complexes of repair DNA polymerase beta with 3'-exonuclease and some other
      proteins were isolated from the chromatin of hepatocytes of normal rats for the
      first time. Biopolymers were extracted from the chromatin by the solution of NaCl
      and Triton X-100. The extract was fractionated by gel-filtration on Sephacryl S
      300 columns successively in low and high ionic strength solutions, on
      hydroxyapatite, and on Sephadex G-100 columns. The complexes have molecular
      weights of 100 and 300 kDa. They dissociate to DNA polymerase and exonuclease in
      the course of chromatography on a DNA-cellulose column or after gel-filtration in
      the presence of 1 M NaCl. The co-purification of the polymerase and exonuclease
      is reconstituted in 0.1 M NaCl. The fidelity of monomeric and composite DNA
      polymerase beta was measured using phage phiX174 amber 3 as a primer/template.
      The products of the synthesis were transfected into Escherichia coli
      spheroplasts, and the frequency of reverse mutations was determined. The complex
      of DNA polymerase beta with 3'-exonuclease was shown to be 30 times more accurate
      than the monomeric polymerase, which can decrease the probability of repair
      mutagenesis and carcinogenesis.

PMID- 18041132
TI  - [Abnormal oogenesis in barfin plaice Pleuronectes pinnifasciatus from the Amursky
      Bay of the Sea of Japan].
AB  - Deformed previtellogenic oocytes, oocytes with incomplete cytoplasm
      vacuolization, and, 2-2.5 month prior to the spawning season, vitellogenic
      oocytes with sites of homogenized yolk have been revealed during oogenesis of
      barfin plaice Pleuronectes pinnifasciatus living in the Amursky Bay, one of the
      most polluted areas in Peter the Great Bay of the Sea of Japan. The early onset
      of yolk homogenization can point to the forthcoming resorption of oocytes in the
      plaice during the spawning season. The number of oocytes with such developmental
      abnormalities varied among females.

PMID- 18041133
TI  - No barriers.

PMID- 18041134
TI  - A friend in deed.

PMID- 18041135
TI  - Home but not alone.

PMID- 18041136
TI  - Personality plus.

PMID- 18041137
TI  - Reel magic.

PMID- 18041138
TI  - 'You cannot be yourself when you are keeping a very important part of you under
      wraps'.

PMID- 18041139
TI  - Being believed by the DWP shouldn't depend on a disinterested or benefits-unaware
      GP.

PMID- 18041140
TI  - What is so very difficult about giving clear information about medication and its
      side effects when you prescribe it?

PMID- 18041141
TI  - Teacher knows best.

PMID- 18041142
TI  - One size doesn't fit all.

PMID- 18041143
TI  - Rights and regulations.

PMID- 18041144
TI  - Essential underpinning.

PMID- 18041145
TI  - Network.

PMID- 18041146
TI  - Anti-HIV agents. Maraviroc approved in Canada.

PMID- 18041147
TI  - Anti-HIV agents. One year clinical trial results with maraviroc.

PMID- 18041148
TI  - Anti-HIV agents.  Maraviroc and resistance.

PMID- 18041149
TI  - Anti-HIV agents. Using maraviroc in first-line therapy.

PMID- 18041150
TI  - Anti-HIV agents. Another receptor blocker--INCB9471.

PMID- 18041151
TI  - Anti-HIV agents. PRO 140--a receptor antibody  for HIV.

PMID- 18041152
TI  - Anti-HIV agents.  Raltegravir (Isentress)--results after  one year.

PMID- 18041153
TI  - Anti-HIV agents. New drugs--hope and  a degree of caution.

PMID- 18041154
TI  - [The British hospital in Safed].

PMID- 18041155
TI  - Leonard Bell Cox (1894-1976)- pioneer of Australian Clinical neurology.

PMID- 18041156
TI  - [Slavery as an indicator of economic performance in 17th-century New Granada].

PMID- 18041158
TI  - Mill's argument for other minds.

PMID- 18041157
TI  - Traumatic ventricular septal defect.

PMID- 18041159
TI  - Leibniz's notion of an aggregate.

PMID- 18041160
TI  - Proceedings of the 47th International Symposium on Regulation of Enzyme Activity
      and Synthesis in Normal and Neoplastic Tissues, September 25-26, 2006, Bologna,
      Italy.

PMID- 18041161
TI  - Relationship between insulin resistance and the renin-angiotensin system:
      analysis for patients with essential and renovascular hypertension.
AB  - Insulin resistance is frequently observed in patients with essential hypertension
      (EHT), and the renin-angiotensin system (RAS) has been demonstrated to modulate
      the status of insulin resistance. The aims of present study are to investigate
      the relationship between systemic RAS and insulin resistance in 82 patients with
      EHT and compare the impact of RAS to insulin resistance with 10 renovascular
      hypertension (RVHT) patients who have a highly activated systemic RAS. From
      patients who were admitted to our hospital, patients with overt diabetes and
      hypertensives who had secondary HT except RVHT or chronic renal failure were
      excluded. Plasma renin activity (PRA) was used as an indicator of systemic RAS
      activity. HOMA-R as an index of insulin resistance and sum of immunoreactive
      insulin (IRI) during glucose tolerance test (sigmaIRI) and IRI at 120 minutes
      (IRI120) were used as indices of hyperinsulinemia. In the EHT patients,
      circulating PRA showed an independent relationship with IRI120 and sigmaIRI after
      adjusting confounding factors (IRI120: t = 2.70, p = 0.01, sigmaIRI: t = 3.05, p
      < 0.001). Excluding patients who were taking angiotensin-converting enzyme
      inhibitors (ACEIs) or angiotensin II type 1 receptor blocker (ARBs), the
      relationship remained in univariate linear regression; after adjustment for
      confounding factors, PRA showed a tendency to be correlated with sigmaIRI.
      However, there was no significant relationship between PRA and indices of insulin
      resistance and hyperinsulinemia in patients with RVHT. In conclusion, the
      systemic RAS may modulate insulin sensitivity in EHT patients.

PMID- 18041162
TI  - Effects of ACE inhibitors or beta-blockers in patients treated with the fixed
      dose combination of isosorbide dinitrate/hydralazine in the African-American
      Heart Failure Trial.
AB  - BACKGROUND: In the A-HeFT (African-American Heart Failure Trial), treatment of
      African-American patients with New York Heart Association (NYHA) class III/IV
      heart failure (HF) with fixed-dose combination (FDC) of isosorbide
      dinitrate/hydralazine (I/H) reduced mortality and morbidity and improved patient
      reported functional status compared with standard therapy alone. OBJECTIVE: To
      examine the benefit of FDC I/H in subgroups based on baseline drug therapy and to
      investigate whether ACE inhibitors and/or angiotensin receptor antagonists
      (angiotensin receptor blockers) [ARBs] or beta-adrenoceptor antagonists (beta
      blockers) provided additional benefit in FDC I/H-treated African-American
      patients with HF. STUDY DESIGN: The A-HeFT was a double-blind, placebo-controlled
      study enrolling 1050 patients stabilized on optimal HF therapies and with NYHA
      class III/IV HF with systolic dysfunction conducted during the years 2001-4 with
      up to 18 months follow-up. The primary endpoint was a composite of mortality,
      first HF hospitalization, and improvement of quality of life at 6 months.
      Secondary endpoints included mortality, hospitalizations, and change in quality
      of life. Prospective Kaplan-Meier survival analyses were used for differences
      between FDC I/H and placebo groups and retrospective analyses were conducted
      within FDC I/H-treated and placebo groups. RESULTS: Subgroup analysis for
      mortality, event-free survival (death or first HF hospitalization), and HF
      hospitalization showed that FDC I/H, compared with placebo, was effective with or
      without ACE inhibitors or beta-blockers or other standard medications with all
      point estimates favoring the FDC I/H group. Within the placebo-treated group,
      beta-blockers or ACE inhibitors and/or ARBs were efficacious in improving
      survival (hazard ratio [HR] 0.33; p<0.0001 for [beta]-blocker use and HR 0.39;
      p=0.01 for ACE inhibitor and/or ARB use). However, within the FDC I/H-treated
      group, use of beta-blockers, but not ACE inhibitors and/or ARBs, provided
      additional significant benefit for survival (HR 0.44; p=0.029 and HR 0.60;
      p=0.34, respectively), event-free survival (HR 0.62; p=0.034 and HR 0.72; p=0.29,
      respectively) and the composite score of death, HF hospitalization and change in
      quality of life (p=0.016 and p=0.13, respectively). CONCLUSION: Based on the
      analysis of baseline medication use in the A-HeFT, FDC I/H was superior to
      placebo with or without beta-blockers or ACE inhibitor. However, beta-blockers
      but not ACE inhibitors and/or ARBs provided additional significant benefit in
      African-Americans with HF treated with FDC I/H. These analyses are hypotheses
      generating and their confirmation in clinical trials needs to be considered.

PMID- 18041163
TI  - Murray F Brennan Fetschrift Symposium, 22-23 April 2006, New York, New York, USA.

PMID- 18041164
TI  - "I am a man!" Race, masculinity, and the 1968 Memphis sanitation strike.

PMID- 18041165
TI  - This haven of rest and health: the Chicago Daily News Sanitarium.

PMID- 18041166
TI  - Sanitation practices, depositional processes, and interpretive contexts of
      Minneapolis privies.

PMID- 18041168
TI  - Catholic nuns and the invention of social work: the Sisters of the Santa Maria
      Institute of Cincinnati, Ohio, 1897 through the 1920s.

PMID- 18041169
TI  - Surviving the Great Depression: orphanages and orphans in Cleveland.

PMID- 18041170
TI  - Infectious diseases and smallpox politics in New Mexico's Rio Abajo, 1847-1920.

PMID- 18041171
TI  - Grazax: an oral vaccine for the treatment of grass pollen allergy (hay fever).
AB  - Grazax is a self-administered, once-daily, tablet-based vaccine that offers an
      alternative to allergy shots for adults with grass pollen allergy (hay fever).
      (2) Evidence from three randomized controlled trials indicates modest
      improvements in hay fever symptoms, with reduced use of medication to control
      symptoms (rescue medication use) in adults who took Grazax compared with placebo.
      No studies have compared Grazax with injection-based allergen immunotherapy. (3)
      It is not yet known if patients treated with Grazax will have a sustained
      tolerance to grass pollen following treatment discontinuation. (4) Adverse
      effects of Grazax are generally mild to moderate local allergic reactions of
      short duration, and include itching and swelling of the mouth, and throat
      irritation. (5) If Grazax becomes widely prescribed and is covered by provincial
      drug plans, the costs to the Canadian health care system and the impact on
      allergy specialist services could be substantial.

PMID- 18041172
TI  - Star Valley, Wyoming: polygamous haven.

PMID- 18041173
TI  - Portable home hemodialysis for kidney failure.
AB  - (1) Home hemodialysis has been in limited use in Canada for some time. Newer,
      portable hemodialysis machines that are easier for patients to operate may
      encourage the uptake of this technology. (2) One portable system is already
      available in the US. The NxStage System One hemodialysis machine operates on
      standard electric current, does not require plumbing or specialized disinfection,
      and is small enough for patients to travel with. (3) It is not yet clear whether
      the use of the NxStage system improves long-term survival and quality of life.
      (4) Home hemodialysis is less costly than conventional in-centre programs, but it
      is unknown whether these savings extend to portable devices.

PMID- 18041174
TI  - Contextual effects of acculturation on perinatal substance exposure among
      immigrant and native-born Latinas.

PMID- 18041175
TI  - Beauty and the beasts.

PMID- 18041176
TI  - Secrets of the Medicare fee schedule.

PMID- 18041177
TI  - Academic viagra: the rise of American masculinity studies.

PMID- 18041178
TI  - Ten means death.

PMID- 18041179
TI  - [Comparison on molecular characteristics of human gamma D-crystallin protein and
      its five mutations].
AB  - OBJECTIVE: To gain further information on the mechanisms underling the
      cataractogenesis by bioinformatics analysis on molecular characteristics of gamma
      D-crystallin (CRYGD) protein and its five cataract-associated mutations. METHODS:
      With the analyzing software in bioinformatics website, we analyzed the (R14C,
      P23T, human wild-type CRYGD protein and the five reported mutations R36S, R58H
      and W156X), focusing on their physical-chemical characteristics, epitopes, post
      translational modification sites, functional domains, secondary and tertiary
      structure. RESULT: R14C, R36S, R58H and W156X mutations resulted in a decrease in
      isoelectric point. R14C brought about a new cysteine residue exposed on the
      molecular surface. A decrease in local charge and a rise in local hydrophobicity
      was found in R14C, R36S and R58H. Local flexibility increased in P23T, while R58H
      caused a fall in local temperature. CONCLUSION: The mutations were shown to cause
      changes in protein surface polarity, hydrophobicity, and spatial structure,
      contributing to protein deposition and cataract formation.

PMID- 18041181
TI  - Proteins associated with the termination of ocular dominance column plasticity in
      Long Evans rats.
AB  - PURPOSE: To investigate the mechanism of the termination of ocular dominance
      column plasticity by electrophysiologic analysis and 2-dimensional
      electrophoresis-mass spectrography (2-DE/MS). METHODS: The changes in ocular
      dominance columns following monocular deprivation were electrophysiologically
      detected in 22-day-old, 100-day-old and chondroitinase-perfused 100-day-old rats.
      Total protein of grey matter of the primary visual cortex was extracted and
      studied by 2-DE/MS from the three groups of rats. RESULTS: Monocular deprivation
      may lead to shifts in ocular dominance columns in 22-day-old and chondroitinase
      perfused 100-day-old rats, but not in 100-day-old rats. Four protein spots
      present in grey matter of the primary visual cortex in 100-day-old, but not in
      that of 22-day-old and chondroitinase-perfused rats, and mass spectrography
      identified two of these proteins. CONCLUSIONS: The electrophysiologic results
      show that ocular dominance column plasticity presents in 22-day-old rats, ends up
      in 100-day-old rats and restored in chondroitinase-perfused 100-day-old rats. 2
      DE/MS results show that phosphatidylethanolamine binding protein and glial
      fibrillary acidic protein delta may be associated with the termination of ocular
      dominance column plasticity in the rat, but need more evidence to confirm it.

PMID- 18041180
TI  - [Detection of serum biomarkers for retinoblastoma using surface enhanced laser
      desorption/ionization protein chip system].
AB  - PURPOSE: To find new serum biomarkers in the serum of retinoblastoma (Rb) patient
      with surface enhanced laser desorption/ionization time-of-flight mass
      spectrometry (SELDI-TOF-MS) and protein chip technique. METHODS: SELDI-TOF-MS and
      IMAC30 and CM10 protein chips were used to analyze the protein profiles from
      serum of 18 patients with Rb and 17 age-matched controls. The protein profiling
      was analyzed statistically by Ciphergen protein chip software 3.0.2. The t-test
      was applied to compare the protein peak intensity. Fisher ratio-test was used to
      compare the predominance of differential protein peaks appeared in patients.
      RESULTS: With IMAC30 protein chips, there were 26 proteins appearing differently
      in serum of patients with Rb compared to normal children. Among them, 21
      proteins, i.e. 7746, 70146, 117136, 30496, 70846, 72,996, 5889, 2544, 12575,
      5489, 9658, 9575, 9929, 10161, 8955, 1886, 10617, 6209, 2411, 7374, 6614 m/z were
      up-regulated and 5 proteins, i.e. 8383, 7923, 7972, 8590, 66576 m/z, down
      regulated (P < 0.001). Using the 7014 m/z protein peak, we could differentiate
      the patients with Rb from the healthy children with a sensitivity of 94.4% and a
      specificity of 82.4%. By CM10 protein chips, 4 proteins, including 3 up-regulated
      proteins (5890, 6097, 7798 m/z) and one down-regulated protein (8593 m/z), were
      detected in Rb patients (P < 0.01). The sensitivity and specificity were 83.3%
      and 70.6% respectively for 7 798 m/z protein. CONCLUSION: There are a few
      candidates of Rb biomarkers in the serum of Rb patient. SELDI Protein Chip
      technology could be a potential method in the clinical screening test of Rb.

PMID- 18041182
TI  - [Retinal gene expression profiles of MNU-induced rat retinal degeneration treated
      with qijudihuangtang].
AB  - PURPOSE: Our previous studies demonstrated that qijudihuangtang, a compound of
      traditional Chinese medicine, protects from MNU (N-methy-N-nitrosourea)-induced
      rat retina photoreceptor injury. The current study was aimed to investigate
      protective effect of qijudihuangtang on the gene expression of retina in the same
      model. METHODS: Thirty 46-day-old female Sprague-Dawley rats were randomly
      divided into three groups (each group, n=10). The rats received a daily
      intragastric administration of qijudihuangtang in drug group, and 0.9% NaCl in
      model and normal groups for 4 days. On the fifth day, the rats in model and drug
      groups received a single intraperitoneal injection of 40 mg/kg body weight of N
      methy-N-nitrosourea (MNU). Equivalent volume of 0.9% NaCl was injected to the
      rats of normal group. After 12 h of injection, all animals were sacrificed. Fresh
      retinas were used to extract total RNA, which was assayed by microarray and real
      time RT-PCR. The differentially expressed genes were also analyzed for the
      functional annotation and signal network mapping. RESULTS: There were 75 and 118
      genes differently expressed (ratio > or = 2.0) in model group versus normal group
      and model group versus drug group, respectively. The former mainly included genes
      upregulated and the latter included most genes downregulated. These genes were
      mainly assigned to the categories binding transcription factor, signaling
      molecular, receptor, nucleic binding and extracellular matrix, and involved
      biological processes including signal transduction, development, immune and
      defense, apoptosis. The differential expressed genes contributed to MAPK
      signaling pathways, Toll-like receptor signaling pathway and apoptosis pathway.
      CONCLUSION: The gene expression in the early stage of MNU-induced rat retinal
      degeneration can be regulated significantly by the administration of
      qijudihuangtang. These changed genes were associated with specific functional
      groups.

PMID- 18041183
TI  - [Aqueous humor penetration of ligustrazine hydrochloride eye drops after topical
      administration in rabbit eyes].
AB  - PURPOSE: To study the aqueous humor penetration of ligustrazine hydrochloride
      after ocular administration in rabbits. METHODS: Eighteen rabbits were randomly
      divided into 6 groups. The aqueous humor was collected at 5, 15, 30, 60, 120 and
      180 minutes following topical administration of ligustrazine hydrochloride eye
      drops and the concentration of ligustrazine hydrochloride was determined by HPLC.
      Analytical column was Diamonsil C18 stainless steel column (250 mm x 4.6 mm, 5
      microm); The mobile phase was methanol: water(62:38); Flow rate was 0.9 ml/min;
      The detection wavelength was 280 nm. RESULTS: The concentrations of ligustrazine
      hydrochloride in aqueous humor were (15.785 +/- 2.988) microg/mL, (11.900 +/-
      1.743) microg/mL, (8.286 +/- 1.182) microg/mL, (2.745 +/- 0.807) microg/mL,
      (0.379 +/- 0.091) microg/mL, (0.049 +/- 0.038) microg/mL, respectively, after a
      time interval of 5 min, 15 min, 30 min, 60 min, 120 min, 180 min. The maximum
      concentration was 15.785 microg/mL at 5 min, and then the concentration of
      ligustrazine hydrochloride gradually decreased and declined to a lower point at
      180 min. CONCLUSION: The penetration of ligustrazine hydrochloride in aqueous
      humor after ocular administration was good. The results provided experimental
      data for the management of eye diseases with ligustrazine hydrochloride by
      topical administration.

PMID- 18041184
TI  - [Effects of all-trans retinoic acid on the rat Muller cell in vitro].
AB  - PURPOSE: To investigate the effects of various concentrations of all-trans
      retinoic acid (RA) on the rat Muller cells in vitro. METHODS: A rat Muller cell
      line was used in this study. Rat Muller cells were cultured with varying levels
      of RA for 24 h to 48 h. We examined cellular morphology under phase contrast
      microscope, cell proliferation using MTT assay, viable cell numbers by
      hemocytometer counting and cell apoptosis with flow cytometry. RESULTS: At lower
      concentration (< 0.1 microM), RA didn't change the cell's appearance and didn't
      inhibit the cell proliferation (P > 0.05). However, at higher concentration (1
      microM, 10 microM, 100 microM), RA could inhibit the proliferation of Muller
      cells accompanied with morphological changes in a time- and dose-dependent
      manner. Furthermore, different concentration of RA (5 microM, 10 microM, 20
      microM) could induce cell apoptosis. When using 20 microM RA to treat cells for
      48 h, a significant decrease in cell numbers and an obvious increment of
      apoptotic cells were observed. The percentage of apoptotic cell was (35.87 +/-
      7.40)% (P < 0.01, vs. control). CONCLUSIONS: RA can inhibit the proliferation and
      induce the apoptosis of muller cells in a time- and dose-dependent manner.

PMID- 18041185
TI  - [The electroretinogram of infants with nystagmus].
AB  - PURPOSE: To find the characteristics and clinical application of
      electroretinogram (ERG) in infants with nystagmus. METHOD: Forty-six cases (92
      eyes) of infants with nystagmus (aged 2-72 months old) were tested with Neuropack
      MEB-2200K system according to the ERG standard of ISCEV. RESULTS: Five kinds of
      ERG responses of all subjects but one could be recorded. The abnormal rates of
      the rod ERG, standard mixture ERG, oscillatory potentials, single-flash cone ERG
      and 30 Hz flicker response were 65%, 86%, 61%, 77% and 62% respectively. The ERG
      abnormalities were evaluated from the 5 responses. The rod ERG decreased in 5
      eyes. The rod-cone ERG decreased in 11 eyes. The cone ERG decreased in 14 eyes.
      The cone-rod ERG decreased in 23 eyes. The standard mixture ERG decreased in 8
      eyes. The ERG was unrecordable in 8 eyes. The mild, middle, and severe decreases
      of rod and cone ERG appeared in 5 eyes respectively. The normal ERG was only
      recorded in 8 eyes. CONCLUSION: Abnormal rate of ERG is 91% in infants with
      nystagmus. The retina abnormality may pay an important role in the pathogenesis
      of nystagmus.

PMID- 18041186
TI  - Eye model for inspecting the image quality of IOLs.
AB  - PURPOSE: To inspect and compare the image quality of an aspheric intraocular lens
      (IQ, Alcon) with those of conventional monofocal silicone and acrylic intraocular
      lens and multifocal intraocular lens (Array). METHODS: The IOLs were tested in
      the eye model, which was designed to be optically equivalent to the theoretical
      eye model. The eye model is a combination of a spherical photographic lens with
      35 mm focal length (IOL put in a water cell) and a charge coupled device (CCD)
      camera. The images constructed by the lenses are observed on a monitor of
      personal computer and the contrasts of the images are analyzed by using
      commercial image processing software. SHARP value is used to measure and estimate
      image definition. RESULTS: The images constructed by changing the diameter of
      aperture stop and IOL. Observed by this eye model, the image definition of
      aspheric intraocular lens (IQ, Alcon) is better than others. DISCUSSION: The
      proposed eye model is useful for testing functional vision and for inspecting the
      differences of intraocular lens.

PMID- 18041187
TI  - [Clinical study of pro 16-slice spiral CT perfusion imaging for high myopia].
AB  - PURPOSE: To study the hemodynamics of the eye-ring's microcirculation in patients
      with high myopia through 16-slice spiral CT perfusion image. METHODS: Twenty
      eight patients (53 eyes) with high myopia and 32 cases with emmetropia (64 eyes)
      in control group were examined by GE lightspeed pro 16-slice spiral CT. The
      perfusion image and the blood volume (BV) of the posterior equatorial eye-ring
      were obtained and analyzed by SPSS 10.0 software. RESULTS: The BV of high myopia
      (4.61 +/- 1.48)ml/ 100 g is significantly less than that of the control group
      (7.72 +/- 1.92)ml/ 100 g (P < 0.01). It implies that the quantity of the small
      vessel and capillary in the eye-ring of the patient with high myopia is less than
      that of the control group. The diopter of high myopia has a significantly
      positive correlation with the BV of the posterior equatorial eye-ring (r = 0.793,
      P < 0.01). CONCLUSION: The perfusion image of 16-slice spiral CT is a quantitive
      method to evaluate the hemodynamics of the high myopia eye-ring's
      microcirculation.

PMID- 18041188
TI  - [Progress in prevalence of primary angle closure glaucoma].
AB  - Glaucoma has long been recognized as a leading cause of irreversible blindness.
      According to data on the epidemiology of glaucoma, primary angle closure glaucoma
      (PACG) is a major form of glaucoma in Asia. This is true especially in
      populations of East Asian and Chinese descent. The characteristics of
      glaucomatous epidemiology continued changing with the developments of society,
      economics and environment. Epidemiologic studies use different diagnostic
      criteria for the definition of PACG as well as what constitutes an occludable or
      narrow drainage angle. This will affect estimates of prevalence of the condition
      in different parts of the world and limit the comparison of published data.
      Furthermore, the prevalence of glaucoma contributed to clinical interference
      decisions. All of above are essential to glaucoma and closely related. The recent
      progress in prevalence of PACG are reviewed as below.

PMID- 18041189
TI  - Evaluating and selecting a chargemaster vendor.

PMID- 18041190
TI  - Do your employees owe you?

PMID- 18041191
TI  - Calculating days in A/R.

PMID- 18041193
TI  - Surviving shift work.

PMID- 18041192
TI  - Alcohol use and injury-related outcomes in older rural trauma patients.
AB  - In summary, people age 65 and older are the fastest growing segment of the United
      States population. As the older population increases, the risk for injuries also
      increases. Several studies have established that use of alcohol is a major
      contributing risk factor for unintentional injury and death in the trauma
      population. The risk is even greater in the older population where smaller
      amounts of alcohol may result in significant impairment and injury. Trauma
      centers provide a systematic approach to the care of the trauma patient and
      provide significant resources to support personnel and services necessary to
      provide care for seriously injured patients. One of the essential elements of a
      trauma system is prevention. This study has supported the need to routinely
      screen older trauma patients for alcohol use at the time of injury event and
      provide intervention strategies. Early identification and assessment of the
      alcohol impaired older trauma patient provides nursing with an opprtunity to
      implement intervention strategies to detect at risk and harmful drinkers and
      provide education on the health risks and consequences of continuing unhealthy
      behaviors. Ultimately this will assist the older trauma patient in reducing
      alcohol consumption and minimize the patient's risk of developing dependence,
      reduce unintentional injuries, reduce subsequent readmissions for recurrent
      injuries, decrease overall health care costs, improve quality of life, and
      decrease morbidity and mortality. This can make a marked impact on public health.

PMID- 18041194
TI  - The communications doctor offers remedies for 11 things that hurt women's career
      success.

PMID- 18041195
TI  - See yourself in 4-D: how to use Appreciative Inquiry to ignite positive change.

PMID- 18041196
TI  - [Epidemiological risk assessment of asbestos-related benign pleural and
      parenchymal changes in workers after past exposure to chrysotile asbestos].
AB  - BACKGROUND: Health effects related with asbestos dust exposure are observed many
      years after its onset. The objective of the study was to evaluate the risk of
      pleural and parenchymal changes depending on the duration of exposure, lapse of
      time since first contact with asbestos dust, and cumulative dust exposure.
      MATERIALS AND METHODS: The study population comprised 222 former workers of
      asbestos processing plants. Risk assessment was based on the results of chest
      radiograms and retrospective exposure measurements. The adjusted odds ratios (OR)
      were used as a relative risk measure and logistic regression models were employed
      in statistical analyses. RESULTS: The risk of diffuse pleural thickening in the
      group of workers exposed to asbestos dust for more than 10 years (years x mg/m3)
      as well as the risk of parenchyma changes, density > or = 1/1, and diffuse
      pleural thickening in the group of workers employed under cumulative exposure to
      asbestos dust for similar period of time were significantly higher than in the
      reference group. No effect of the lapse of time since first contact with asbestos
      dust on the risk of analyzed radiological changes was observed in the study
      group. CONCLUSIONS: The level of cumulative exposure to asbestos should be taken
      into account in the recommended frequency of preventive medical examinations of
      workers.

PMID- 18041197
TI  - [Assessment of occupational exposure to photon rays in Poland, 2006].
AB  - BACKGROUND: This paper reports the results of the measurement of ionizing
      radiation doses in people occupationally exposed to gamma or X-ray radiation in
      Poland, 2006. MATERIALS AND METHODS: The whole-body dose measurements were
      performed by film dosimeter method, while the hand skin dose measurements were
      done using thermoluminescence dosimeters, according to AB327 (1) accreditation
      procedures. RESULTS: In 2006, the whole-body measurements were performed in 3161
      people employed in 3635 institutions, while the hand measurements were performed
      in 805 workers of 62 institutions. Mean Hp(10) dose was 0.49 mSv, whereas mean
      Hp(0.07) dose was 7.5 mSv. CONCLUSIONS: Having compared the 2006 data with those
      obtained over the earlier years, it is evident that occupational exposure to X
      rays has remained at the same level and the radiological protection in the health
      care sector is satisfactory.

PMID- 18041198
TI  - [An analysis of selected hands hygiene habits in selected population of nursing
      staff].
AB  - BACKGROUND: Hand washing and disinfection in the regular nursing practice is the
      cheapest and the most effective way to decrease hospital infections by preventing
      the microorganism transmission among patients. An attempt to analyze hand hygiene
      habits among nurses was the aim of this study. MATERIALS AND METHODS: A randomly
      selected group of 150 nurses (146 women and 4 men, aged 22-56, mean, 32 years)
      participated in the study. RESULTS AND CONCLUSIONS: The obtained results allow to
      state that hygiene rules concerning hand washing and disinfection were followed
      by the members of the study group during performing most of the operations. The
      only exception were procedures applied when nursing and assisting patients. The
      nurses reported irritating properties of disinfectants as the most common reasons
      for neglecting hand hygiene. However, they also pointed to other reasons, such as
      lack of hand washing habit, laziness, lack of awareness among nurses, negligence,
      routine, thoughtlessness, lack of disposable towels, and shortage of nursing
      staff. A statistically significant difference in hand hygiene behavior was found
      between nurses from surgical and non-surgical wards.

PMID- 18041199
TI  - [Exposure to aggression at work in the health care and public service sectors].
AB  - BACKGROUND: The aim of the study was to assess the frequency and forms of violent
      behavior against nurses and service sector workers. MATERIAL AND METHODS: The
      subjects under the study were 1163 nurses and 391 service sector workers (public
      transport and postal services) aged 19-63 years. Subjects were asked to fill in
      the survey questionnaire "Exposure to Aggression", which consists of 32 items and
      allows for assessing the frequency of acts of aggression (both physical and
      psychical) against employees in a one year period. RESULTS: Clients and patients
      were the most common source of aggression in the group of employees under study;
      around 90% of them experienced various forms of verbal abuse. Every second
      employee was the subject of supervisor's aggression. It was also found that more
      than 20% of public transport workers and around 14% of nurses were physically
      abused by their clients or patients. The collected data show that aggressive
      behaviors at work is a serious and challenging problem that may affect the
      performance and health of employees.

PMID- 18041200
TI  - [Type D personality, coping with stress and intensity of PTSD symptoms in
      firefighters].
AB  - BACKGROUND: Personality traits and coping strategies are regarded as determinants
      of post-traumatic stress disorder (PTSD) symptoms in persons who have experienced
      a traumatic event. The purpose of the study was to investigate the relationship
      between type D personality, coping strategies, and PTSD symptoms. MATERIAL AND
      METHODS: A group of 190 firefighters of life-saving units of the State Fire
      Brigade, Lodz, participated in the study. Their mean age was 33.5 years and their
      mean duration of employment was 9.2 years. Survey, the Impact Event Scale, the
      DS14 scale, and Mini-COPE were used as the study techniques. RESULTS: The data
      obtained from the study confirm the relationship of both dimensions, comprising
      type D personality and maladaptive strategies with the increased level of PTSD
      symptoms. CONCLUSIONS: A tendency to experience strong negative emotions
      (negative affectivity) and coping strategies, such as self-distraction and
      behavioral disengagement increase the intensity of PTSD symptoms, intrusion in
      general, and hyperarousal in particular.

PMID- 18041201
TI  - [Work-related stress and the Conservation of Resources Theory by Stevan Hobfoll].
AB  - BACKGROUND: The Conservation of Resources Theory by Stevan Hobfoll has grown in
      popularity, as a new theory of stress, since the 1980s. A general assumption of
      Hobfoll's theory is that an individual has some resources at his/her disposal
      which he/she greatly appreciates and is inclined to protect and never loose them.
      Stress is predicted to occur as a result of circumstances that represent: (1) a
      threat of resource loss, or (2) an actual loss of the resources required to
      sustain the individual, and (3) the lack of reasonable gain following resource
      investments. Hobfoll has developed the Conservation of Resources-Evaluation (COR
      E) questionnaire as an instrument derived from his theory to measure the degree
      of lost and gained resources. The questionnaire has been adapted to Polish
      conditions. The aim of the study was to assess the usefulness of COR-E in the
      diagnosis of work-related stress. In the literature, we have found information on
      the relationship between COR-E results and depressive mood, anxiety and other
      stress effects. But it should be remembered that these effects are not caused
      only by stress. We would like to check whether COR-E results are correlated with
      the results of the stress at work questionnaire. MATERIAL AND METHODS: The study
      group comprised 157 persons. Each person completed two questionnaires: COR-E (in
      Polish version) and Subjective Assessment of Work Characteristics. The later has
      been developed to measure stress at work according to the psychosocial factor
      approach. RESULTS: There was no relationship between reported gains of resources
      and work stress, but we found very low correlation between reported lost
      resources and work stress (r = 0.16; p < 0.05). Item analyses revealed that the
      loss of some resources was correlated with work stress. However, much higher
      correlation was observed between the results of a subscale consisting of these
      items and work stress (r = 0.40; p < 0.01). CONCLUSIONS: The COR-E questionnaire
      can be accepted as a new instrument to measure work stress, but further
      investigations are needed to cover other occupational groups.

PMID- 18041202
TI  - [Backgrounds for assessing occupational exposure to crystalline silica dust in
      Poland and worldwide].
AB  - Crystalline silica is an agent harmful to human health, and quite frequently
      present in occupational environments. Occupational groups exposed to crystalline
      silica dust include mostly workers of the mineral and coal mining as well as
      metallurgical, chemical and construction industries. In the European Union (EU),
      the number of those exposed to this agent is estimated at over 2 million persons.
      In Poland, the number of people employed under conditions of excessive silica
      dust exposure exceeds 50 thousand. The assessment of occupational exposure to
      crystalline silica comprises several steps: primarily workplace determinations,
      quantitative sample analyses and comparisons of the obtained results with
      admissible values. This work describes a set of instruments that enables direct
      comparison of the study results with admissible values binding in almost 40
      countries. It also highlights the consequences resulting from the classification
      of quartz and cristobalite, the most common forms of crystalline silica, as
      carcinogens by the International Agency for Research on Cancer (IARC). A survey
      of air sampling and dust determination methods used in various countries to
      measure airborne dust concentrations of crystalline silica in occupational
      environments are presented along with relevant tables. The GESTIS data base,
      specifying the methods considered by EU as suitable for measuring and assessing
      harmful agents, was used as the selection criterion. Particular attention was
      paid to the methods used to determine crystalline silica; the effect of
      analytical methods applied, sample preparation procedures, and reference
      materials on the results of determinations was also analyzed. Main parameters of
      method validation, such as detection and determination limits, and precision of
      the analysis were compared.

PMID- 18041203
TI  - [Occupational and environmental exposure to organophosphate insecticides:
      exposure markers and health effects. A review paper].
AB  - This paper presents a review of publications on environmental and occupational
      exposure to organophosphate insecticides. Markers used in evaluation of exposure
      and health effects are also discussed. The special attention was paid to exposure
      of children and pregnant women.

PMID- 18041204
TI  - [The incidence of tuberculosis in Poland and other E.U. countries and the Russian
      Federation, Belarus and Ukraine: implications for prophylactic activities].
AB  - Over the last 50 years, the number of new cases of tuberculosis (TB) has dropped
      significantly in the native population of several industrialized countries, while
      at the same time the steady increase in TB incidence was noted in Polish
      residents born elsewhere. Since Poland is facing an increase in the number of
      foreigners applying for permanent or long-term residence permit, the evaluation
      of potential impact of this situation on TB incidence in our country seems
      necessary. Based on the recent WHO data, TB incidence in Poland, fifteen old and
      twelve new European Union members, which joined the Union in 2004 and 2007 as
      well as in three neighbor countries, was compared. Screening tests for
      tuberculosis are not usually covered by pre-entry examinations of foreign workers
      seeking employment in Poland, therefore, it is proposed to extend screening
      programs organized by local health departments to cover residents of foreign
      countries.

PMID- 18041205
TI  - [Work performance as a risk factor for carpal tunnel syndrome].
AB  - Certification of carpal tunnel syndrome (CTS) as an occupational disease should
      be based on evidence that the job performance is a dominant factor responsible
      for its development. Features of the way the job is performed, which can increase
      the constriction in carpal tunnel and their quantitative analysis are presented.
      They include a specific position of the hand during the job performance (dorsal
      bending, alternate bending and extension), e.g., overcoming resistance with
      fingers, pincher grip, object catching and holding, exerting pressure on the
      hand, repeated movements or work with vibratory tools. These features
      characterize work of persons employed in meat processing, fitting of sub
      assemblies, packing of products, or employed as supermarket cashiers. CTS
      occurrence in persons working with computers and thus using a keyboard or a mouse
      is now greatly limited owing to the improvement in ergonomic parameters of
      computer-equipped workposts. The paper indicates CTS risk factors (carpal tunnel
      size, post-traumatic lesions, rheumatoid arthritis, female gender, hormonal
      changes during menopause and pregnancy, and other hormonal disorders like
      hypothyreosis, diabetes, obesity, hypercholesterolemia, cigarette smoking, high
      alcohol consumption), which have been very well evidenced. In the summary, the
      attention was also paid to improper estimation of burden to upper limbs by
      listing jobs performed and stressing the need to quantitatively define hand
      burdening factors and estimate duration of such burdens.

PMID- 18041206
TI  - [Combined treatment for Moya-Moya disease, by using direct anastomosis and
      revascularization: experience of 225 operations].
AB  - The results of 225 operations made in 140 patients with Moya-Moya disease are
      analyzed. All the patients had clinical manifestations of this disease and were
      examined in accordance with the approved protocol of the Unit of Neurosurgery,
      Nagoya Daini Red Cross Hospital (Nagoya, Japan). The examination included
      computed tomography, magnetic resonance imaging, magnetic resonance angiography,
      preoperative angiography, single photon emission computed tomography with
      acetazolamide challenge. The surgical method consisted of a combination of direct
      arterial microanastomosis and indirect synangiosis (EMS, EDAS, EGS, cranial burr
      hole). The number of surgical complications was minimal (2.9%). There were
      excellent and good clinical results (disappearance of clinical symptoms or
      clinical improvement) in 92.9% of cases. Postoperative examinations confirmed the
      high percentage of positive results as cerebral circulation normalization in
      97.1% of cases. The results of surgical treatment provided strong evidence that
      progression of the disease could be prevented.

PMID- 18041207
TI  - [The specific features of clinical manifestations and surgical treatment of
      spastic and pain syndromes after injury to the vertebral column and spinal cord].
AB  - The purpose of the investigation was to study the clinical manifestations of
      spastic syndrome after injury to the vertebral column and spinal cord and to
      devise its surgical treatment policy. The investigation included 21 patients with
      significant spasticity or pain syndrome after severe injury to the vertebral
      column and spinal cord without any potential of motor recovery. All the patients
      were observed to have severe inferior paraplegia, cacesthesia following the
      radicular and conduction with total hypo- or anesthesia. Pain was rated, by using
      the visual analogue scale and the McGill questionnaire, spasticity was estimated
      by the Ashworth scale. The patients' motor activity was also evaluated. Bilateral
      rhizomyeolotomy of the dorsal root entry zone (DREZ) was performed in 10 patients
      with pain syndrome; posterior partial rhizidiotomy was made in 8 patients with
      spastic syndrome; 3 patients underwent epidural spinal cord stimulation. Groups
      with a preponderance of pain (47%) and spastic (53%) syndromes were identified. A
      clinically equal combination of spastic and pain components occurred rarely. Pain
      was maximally pronounced, neuropathic, metamerically radicular, in dermatomes
      from the level of injury. Leg spasticity was more marked and concurrent with
      contracture. The efficiency of lateral rhizomyelotomy of DREZ in the treatment of
      pain was 89% in the early period and 63% in the late (as long as 4 years) one.
      That of bilateral posterior partial rhizodiotomy in the treatment of spasticity
      was 75 and 75% in the early and late (as long as 2.5 years), respectively.
      Rhizomyelotomy of DREZ is a pathogenetically grounded and effective procedure
      when there is a preponderance of neuropathic metamerically radicular pain from
      the level of injury. Bilateral posterior partial rhizidiotomy is the method of
      choice in treating significant spasticity.

PMID- 18041208
TI  - [Surgical treatment for anterior cerebral hernias].
AB  - The paper describes the authors' experience in treating 22 patients aged 2 months
      to 16 years who had congenital anterior cerebral hernias. A comprehensive
      principle that consists in removing hernial defects of the pachymeninx and skull
      base, excising herniation, and performing reconstructive operations in
      concomitant craniofacial deformities was used in the treatment of children with
      anterior encephalocele. All these surgical procedures were, if possible,
      performed in one step. There were no recurrent cerebral hernias and nasal
      liquorrhea was also absent. There was no progression of neurological symptoms in
      all patients. None patient developed meningitis or other infectious
      complications. All the parents recognized the cosmetic results of surgery as
      satisfactory. Three cases of different variants of this pathology are presented
      as an illustration of current surgical treatment.

PMID- 18041209
TI  - [Pulmonary thromboembolism in neurosurgical patients. Part 3. Analysis of the
      clinical effectiveness and safety of combined prevention of thromboembolic events
      in neurosurgical patients in the perioperative period].
AB  - The paper presents the results of clinical evaluation of combined prevention of
      leg deep vein thrombosis and pulmonary thromboembolism in 130 neurosurgical
      patients undergoing intracranial interventions for brain tumors. Combined
      prevention comprises mechanical (compression knitted wear + periodic pneumatic
      leg compression by a special device) and pharmacological (subcutaneous injection
      of low molecular-weight heparins on postoperative day 2, followed by the daily
      administration of acetylsalicylic acid from the moment of a patient's activation)
      treatments. The study has indicated that this preventive procedure is effective
      and at the same time safe against the development of intracranial hemorrhagic
      complications.

PMID- 18041210
TI  - [Spontaneous anterior meningeal arterial aneurysmal rupture].
AB  - The paper describes a rare case of a patient with spontaneous rupture of
      nontraumatic anterior meningeal arterial aneurysmal rupture. The patient
      underwent clipping of the neck of the aneurysm and its excision. A detailed
      account of intraoperative signs of this aneurysm is given. Angiographic and
      morphological data and the morphological pattern confirming the true pattern of
      the aneurysm are presented.

PMID- 18041211
TI  - [Chondroblastoma of the skull base].

PMID- 18041212
TI  - [Intraoperative radiotherapy by means of a photon radiosurgical system (PRS400)
      after removal of recurring glioblastoma].

PMID- 18041213
TI  - [Comprehensive approach to treating cranial ependymomas in children].

PMID- 18041214
TI  - [Stereotactic radiosurgury for intracerebral metastases by means a "Leksell Gamma
      Knife" unit].

PMID- 18041215
TI  - [On the 70tn anniversary of discovery of tick-borne encephalitis virus in the Far
      East of Russia].

PMID- 18041216
TI  - [The 70th anniversary of discovery of tick-borne encephalitis. A path to true
      history].
AB  - The discovery of tick-borne encephalitis (TBE) in the Far East of the USSR in
      1937 is marked by investigators' heroism and tragedies--diseases in the members
      of the expedition and deaths when the first vaccine was designed in 1938. The
      head of the expedition L. A. Zilber and two specialists were arrested on a charge
      of subversive activities--spreading Japanese encephalitis in the guise of
      discovering a new virus. The paper presents the archival records and
      recollections of the members of the far-eastern expedition, which specify the
      history of TBE discovery.

PMID- 18041217
TI  - [Organization of supervision of tick-borne encephalitis and ways of its
      prevention in the Russian Federation].
AB  - The paper presents the data characterizing the epidemiological situation
      associated with tick-borne virus encephalitis (TBVE) in the Russian Federation in
      2006. There is a 22.7% reduction in morbidity as compared with 2005; however, the
      situation is considered to be of strain; a rise in the incidence of TBVE is
      recorded in a number of subjects of the Russian Federation. There is a high
      activity of natural and anthropurgic foci of TBVE; there are as many as 250
      recourses to a doctor for tick bites. In some regions, tick virus carriage has
      been established at 13-29%. TBVE vaccination coverage is quite insufficient; in
      many cases emergency prophylaxis is not made due to the fact that specific
      immunoglobulin is in short supply whereas some areas continue to unwarrantedly
      inject a serum for lack of rapidly tick virus-determining laboratories. There are
      essential faults in the organization of acaricidal measures and in the propaganda
      of knowledge of personal TBVE prophylaxis in the population. Tasks for increasing
      the level of comprehensive prophylaxis are defined to substantially reduce TBVE
      morbidity in the Russian Federation.

PMID- 18041218
TI  - [Molecular genetic characteristics of tick-borne encephalitis virus].
AB  - Flaviviruses from a tick-borne encephalitis virus (TBEV) complex circulate in
      about all the countries widely distributed in Northern Eurasia. Complete
      nucleotide sequences for genomes of different 15 tick-borne encephalitis viruses
      have been determined in the past years. Phylogenetic analyses of these sequences
      showed their significant genetic variability. Thus, the genetic differences in
      the genomes of TBEV strains are as high as 17.3%, but the differences in the
      amino acid sequences are 9%. These genetic differences permit determination of
      the time of divergence of the current TBEV genovariants from the common viral
      precursor in 1700 to 2100. Novel genetic variants of the Far-Eastern TBEV
      subtype, which are represented by Senzhang and Glubinnoe/2004 viruses, have been
      discovered in the pastyears. New variants of the same Far-Eastern subtype of
      TBEV, which are able to induce hemorrhagic tick-borne encephalitis, have been
      found in Western Siberia. The fact that there are considerable genetic
      differences in Turkish and Spanish sheep encephalitis viruses has been
      established within the European subtype of TBEV. The Siberian subtype of TBEV is
      genetically more uniform; however co-circulation of the Far-Eastern and Siberian
      subtypes of TBEV has been found in the natural TBEV foci of Siberia. This
      suggests that there may be at present a change in the genotypes of TBEV in
      different geographical regions.

PMID- 18041219
TI  - [Evolution of tick-borne encephalitis and a problem of evolution of its causative
      agent].
AB  - The evolution of tick-borne encephalitis (TBE) is marked by the expanded
      nosological area, the transformation of landscapes, the formation of anthropurgic
      foci, the change of environmental systems, the increase of mortality rate mainly
      among urban dwellers, as well as pathomorphism. The evolution of natural TBE
      virus (TBEV) populations was studied in Eastern and Western Siberia, Middle
      Urals, and the European part of the nosological area. The paper first describes
      the types of evolutionary transformations of viral populations under the
      conditions of a varying environmental and epidemiological situation. These
      include: 1) the change of TBEV subtypes over 50-60 years; substitution of the Far
      Eastern subtype for its Siberian subtype (the Sverdlovsk and Kemerovo regions);
      2) the steady-state circulation of one Siberian subtype with mutanttypes being
      accumulated (the Vologda region); 3) co-existence of the Far-Eastern and Siberian
      subtypes with the common vector Ixodes persulcatus (the Yaroslavl and Irkutsk
      regions, etc.); 4) original mixed TBEV strains including the gene sites of
      proteins E and NSI of two subtypes. There is new evidence that the Siberian
      subtype is able to induce focal TBE forms, leading to death.

PMID- 18041220
TI  - [The present knowledge of tick-borne encephalitis vectors].
AB  - The most important aspects of the relationships of tick-borne encephalitis virus
      and its vectors--Ixodes ticks. These include the establishment of a rule of viral
      exchange between the co-fed ticks, which makes its reverse transfer from nymphs
      to larvae possible; enhancement of tick aggressiveness under the influence of the
      incremental concentrations of the virus increasing their epidemiological danger;
      the association of the spread of viral genospecies with the genetic structure of
      tick populations; the emergence of phenotypically different vector subpopulations
      with new vector properties (under the influence of anthropogenic factors); and
      the elucidation of a possible role of the virus as an enhancer in mixed viral and
      bacterial infections of tick vectors.

PMID- 18041221
TI  - [Prevention of tick-borne encephalitis at the present stage: strategy and
      tactics].
AB  - The paper discusses the prevention of tick-borne encephalitis (TBE) under the
      conditions of a varying epidemiologic situation. High mortality, a change in its
      structure, an expansion of a nosological area, an increase in the number of
      anthropurgic foci in the suburbs and towns and cities, the detection of combined
      foci and the development of mixed forms of tick-borne infections, and clinical
      pathomorphism suggest that novel approaches to preventing this severe viral
      disease are urgent. The comprehensive nature of a prophylaxis system should
      envisage the use of tried-and-true specific and nonspecific measures against the
      entire group of tick-borne infections. Cohort vaccination should be considered as
      a priority measure in high TBE endemic areas. The prophylaxis system should be
      differentiated and adequate to the specific epidemic situation in the endemic
      regions.

PMID- 18041222
TI  - [Prevention of tick-borne encephalitis: current aspects].
AB  - The authors consider the present tick-borne encephalitis situation in our country
      and prospects for this infection control.

PMID- 18041223
TI  - [Current aspects of the clinical picture of tick-borne encephalitis].
AB  - Based on the long-term follow-up of 655 patients with different forms of tick
      borne encephalitis (TBE), the authors describe its present clinical
      characteristics in the Baikal natural focus. They have established the
      preponderance of the meningeal form of the infection and the relatively severe
      course with residual phenomena and a fatal outcome in patients with the
      poliomyelitic form of TBE.

PMID- 18041225
TI  - [The metabolic syndrome and risk of stroke in a rural community in Japan].
AB  - PURPOSE: To clarify the association between the metabolic syndrome (MS) and
      stroke incidence with a prospective cohort study in a rural community. METHODS:
      We selected 4,627 people aged > or =40 years without any past history of stroke
      from total 4,672 participants of health checkups during 1996 to 1998 in O City,
      Ehime prefecture. These were followed until Dec 31, 2002 and assessed for
      incident stroke based on the stroke registration system in the whole community.
      MS was defined using baseline data for waist circumference and three risk
      factors: elevated blood pressure, dyslipidemia, and glucose intolerance. Sex and
      age-adjusted relative risks (RR) for incident stroke were estimated using Cox's
      proportional hazard model, and population attributable risks (PAR) were also
      calculated. RESULTS: During the mean 5.7 year-follow-up, 88 incident strokes (50
      in men and 38 in women) were recorded; 11.4% cerebral hemorrhage; 5.7%
      subarachnoid hemorrhage; and 83.0% cerebral infarction. Percentages of
      individuals with MS in the stroke and non-stroke groups were 6.8% and 6.4%,
      respectively, with no significant different between the two. The highest PAR was
      found among individuals with a normal waist and one risk factor (36.3%). The sex
      and age-adjusted RR for MS and incident stroke was not significantly elevated,
      using subjects with a normal waist circumference and 0 risk factors as a
      reference group (RR, 1.00); however, the RR of persons with a normal waist level
      plus one or more risks was 2.53 (95% CI, 1.14-5.58), and that for individuals
      with a high waist circumference and > or = 1 risk factors, including MS, was 2.66
      (95% CI, 1.14-6.21). CONCLUSION: The risk of incident stroke is increased in
      people with risk factor aggregation, regardless of visceral fat conditions. Since
      the PAR was higher for people with a normal waist circumference than a high waist
      circumference in this population, the results suggest that a health policy
      focusing on MS for stroke prevention would not be effective in rural communities
      in Japan.

PMID- 18041226
TI  - [Trends in mortality from intractable diseases in Japan, 1972-2004].
AB  - PURPOSE: In 1972, the Ministry of Health, Labour and Welfare of Japan defined
      intractable diseases as those with unknown etiology, no established treatment
      regimens, and severe sequelae of physical, mental and social difficulties. Since
      then, the Ministry has promoted scientific research on these diseases and offered
      financial support to those suffering from their effects. The purpose of the
      present study was to analyze trends in deaths from the diseases in Japan over the
      period from 1972-2004. METHODS: For the selected intractable diseases with 100
      deaths or more per year, crude (CDR) and direct age-standardized death rates
      (ADR) were computed using the national underlying-cause-of-death mortality
      database of Japan based on International Classification of Diseases. Joinpoint
      regression analysis was applied to identify significant changes in the trends.
      RESULTS: The CDRs in the latest observed year per 1 million persons/year) for
      males and females were 25.55 and 25.93, respectively, for Parkinson's disease,
      5.41 and 6.92 for aplastic anemia, 0.87 and 3.50 for systemic lupus
      erythematosus, 2.93 and 2.36 for amyloidosis, 1.40 and 1.54 for polyarteritis
      nodosa, 1.34 and 1.61 for idiopathic thrombocytopenic purpura, and 1.02 and 0.74
      for ulcerative colitis. The respective annual percentage changes (APCs) for males
      and females during the overall period decreased for ulcerative colitis (-5.2% and
      -7.5%), aplastic anemia (-3.6% and -3.7%), idiopathic thrombocytopenic purpura (
      2.1% and -3.0%), and systemic lupus erythematosus (-0.9% and -2.6%), while the
      APCs increased for amyloidosis (+3.3% and +3.5%), polyarteritis nodosa (+3.2% and
      +4.0%), and Parkinson's disease (+0.7% in males alone). With the APCs in the
      latest trend phase, polyarteritis nodosa and Parkinson's disease in females
      showed appreciable declines; on the other hand, amyloidosis in males demonstrated
      the significant increase, and ulcerative colitis in males exhibited an apparent
      leveling off of the decline. CONCLUSION: The ADRs for most of the intractable
      diseases have declined significantly in Japan over the last 3 decades. The
      decline might be attributed in large part to improved diagnosis and treatment
      because of the lack of effective primary prevention measures. Support for the
      affected patients and further research on etiology and radical cure of the
      diseases must be considered necessary.

PMID- 18041224
TI  - [Complex environmental and virological monitoring in the Primorye Territory in
      2003-2006].
AB  - The paper presents the results of monitoring of viruses of Western Nile (WN),
      Japanese encephalitis (JE), tick-borne encephalitis (TBE), Geta, Influenza A, as
      well as avian paramicroviruses type I (virus of Newcastle disease (ND)) and type
      6 (APMV-6) in the Primorye Territory in 2003-2006. Totally throughout the period,
      specific antibodies to the viruses were detected by neutralization test in wild
      birds (7.3%, WN; 8.0%, Geta; 0.7% Batai; 2.8%, Alpine hare (Lepus timidus); by
      hemagglutination-inhibition test in cattle (11.4% WN; 5.9%, JE; j 3.0%, TBE;
      11.6%, Geta), horses (6.1, 6.8, 0, and 25.3%, respectively), and pigs (5.4, 1.5,
      0, and 5.9%, respectively) by enzyme immunoassay (IgG) in human beings (0.8, 0.5,
      6.8, and 3.2%, respectively. Reverse-transcription polymerase chain reaction (RT
      PCR) was used to reveal RNA of the NP segment of influenza A virus in 57.9 and
      65% of the cloacal swabs from wild and domestic birds, respectively; and the HA
      segment of subtype HH was not detected in 2005. HA/H5 RNA was recorded in 5.5 and
      6.7% of the swabs from wild and domestic birds, respectively; 6% of the specimens
      from domestic birds were M-segment positive in 2006. RNA of influenza A virus
      NA/H7 and RNA was not detected throughout the years. In 2004, the cloacal swabs 8
      isolated influenza A strains: two H3N8 and two H4N8 strains from European teals
      (Anas crecca), two (H3N8 and H6N2) strains from Baikal teals (A. formosa), one
      (H10N4) strain from shovelers (A. clypeata), and one (H4N8) from garganeys (A.
      querquedula). In 2004, one ND virus strain was isolated from the cloacal swabs
      from European teals (A. crecca). RT-PCR revealed RNA of this virus in some 8 more
      cloacal swabs from black ducks (A. poecilorhyncha) (3 positive specimens),
      pheasants (Phasianus colchicus) (n = 2), garganeys (A. querquedula) (n = 1),
      gadwalls (A. strepera) (n = 1), and geese (Anser anser domesticus) (n = 1).
      Sequencing of the 374-member fragment of the ND virus F gene, which included a
      proteolytic cleavage site, could assign two samples to the weakly pathogenetic
      variants of genotype 1, one sample to highly pathogenic variants of genotype 3a,
      five to highly pathogenic ones of genotype 5b. Isolation of APMV-6 (2003) from
      common egrets (Egretta alba) and geese (Ans. anser domesticus) is first
      described.

PMID- 18041228
TI  - [Relationships between smoking and the health locus of control among junior high
      school students].
AB  - PURPOSE: To clarify effects of the Health Locus of Control (HLC) on smoking
      behavior, relationships between smoking and HLC among junior high school students
      were examined. METHODS: The subjects of the initial study, conducted in 1991,
      were public elementary schoolchildren in their 3rd year (11-12 years old). We
      then investigated the same children again in 1994 and 1997. We here mainly used
      data for 265 students (136 males and 129 females) obtained in 1997 when they were
      public junior high school students in their 3rd year (14-15 years old).
      Questionnaires included items on smoking experience, smoking intention and the
      Parcel & Meyer's Children's HLC scales. RESULTS: 1. Smoking experience was not
      associated with the HLC. 2. Concerning smoking intention among boys, the neutral
      group expressed stronger beliefs in the powerful others HLC in 1994 and 1997 than
      the positive group. In addition, the positive group expressed weaker beliefs in
      the powerful others HLC in 1994 than the negative group. 3. Concerning smoking
      intention among girls, the neutral group expressed stronger belifs in the
      powerful others HLC in 1997 than the negative group. CONCLUSION: Smoking
      experience was not associated with the HLC. However, smoking intention was
      significantly associated with beliefs in the powerful others HLC. In this regard,
      the neutral group tended to have strong beliefs in the powerful others HLC
      suggesting that students in this group might be easily affected by other people
      in both positive and negative ways. In other words, they must be guided in a good
      fashion through appropriate health education.

PMID- 18041227
TI  - [Age and cause of death contributing to reduction of disparity in age-adjusted
      overall mortality between males in Okinawa and mainland Japan].
AB  - OBJECTIVES: We here propose a new index, the difference-change contribution
      proportion, to quantify contributions of age and cause of death to differences in
      age-adjusted overall mortality disparities between two groups over time. The
      present study was conducted with the aim of elucidating age and cause of death
      contributions to the recent decrease in disparity in life expectancy between
      males in Okinawa and mainland Japan. The longer-term goal is to apply the
      findings to developing appropriate preventive measures against diseases for
      Okinawa people. METHODS: Changes in disparity between age-adjusted overall
      mortality of male populations of Okinawa and Japan nationwide during a 15-year
      period, between 1985 and 2000, were measured and difference-change contribution
      proportions for age-adjusted overall mortality were computed. RESULTS: Causes of
      death that showed high difference-change contribution proportions included
      cerebral infarction (24.26%), cardiac failure (18.45%), other cerebrovascular
      diseases (15.11%), malignant gastric neoplasms (11.89%), ischemic heart disease
      (11.06%), hepatic disease (10.93%), suicide (5.71%), and diabetes (5.36%). Of
      these, cerebral infarction, cardiac failure, other cerebrovascular diseases,
      malignant gastric neoplasm, ischemic heart disease, and diabetes indicated high
      difference-change contribution proportions among seniors 65 years old and above,
      while hepatic disease and suicide ranked highly among the middle-aged.
      CONCLUSION: The results of this study revealed the extent of age and cause of
      death contributions to the decreasing disparity observed between populations of
      Okinawa and Japan nationwide in male age-adjusted overall mortality. The causes
      of death and the age revealed by this study are critical to taking preventive
      measures against diseases. Moreover, this study confirmed that the difference
      change contribution proportion is a useful method to quantify contributions of
      age and cause of death to changes in variation regarding life expectancy.

PMID- 18041229
TI  - [Analysis of parents' thoughts regarding their judgments and responses when their
      children were suddenly taken ill: parents' fear, peace of mind, coping behavior
      and demands of government in the free-answer question].

PMID- 18041230
TI  - From my perspective. The fragmented and labyrinthine schematics that define our
      current health care system regularly frustrate surgeons' efforts to deliver, and
      patients' attempts to receive, optimal care.

PMID- 18041231
TI  - The surgical hospitalist: a new solution for emergency surgical care?

PMID- 18041232
TI  - Trauma funding for Tennessee: the incredible journey.

PMID- 18041233
TI  - 2007 state legislative activity.

PMID- 18041234
TI  - Evidence-Based Reviews in Surgery to begin its seventh year.

PMID- 18041235
TI  - A roadmap to safe surgical care: a view from Pennsylvania.
AB  - An effort to make operations safe is realistic if surgeons are committed. Such an
      effort involves educating surgeons about safe practices based on current
      knowledge of best practices, including team training and talking to patients. It
      involves identifying leaders and developing appropriate infrastructure for
      academic activities. It also involves the collection of information needed to
      identify safe and unsafe situations. The potential advantages of a drive for safe
      surgery should be fewer complications, less care per patient, lower costs, and
      less liability.

PMID- 18041236
TI  - Spreadsheet to the bed sheet.

PMID- 18041237
TI  - NTDB datapoints: walk the line.

PMID- 18041238
TI  - Randomized prospective comparison of visian toric implantable collamer lens and
      conventional photorefractive keratectomy for moderate to high myopic astigmatism.
AB  - PURPOSE: To compare the Visian Toric Implantable Collamer Lens (TICL), a toric
      phakic intraocular lens (IOL), and photorefractive keratectomy (PRK) in the
      correction of moderate to high myopic astigmatism. METHODS: This prospective,
      randomized study consisted of 43 eyes implanted with the TICL (20 bilateral
      cases) and 45 eyes receiving PRK with mitomycin C (22 bilateral cases) with
      moderate to high myopia (-6.00 to -20.00 diopters [D] sphere) measured at the
      spectacle plane and 1.00 to 4.00 D of astigmatism. All patient treatment and
      follow-up occurred at the Naval Medical Center San Diego. Study follow-up was 1
      day, 1 week, 1, 3, 6, and 12 months postoperative. RESULTS: Mean best spectacle
      corrected visual acuity (BSCVA), change in BSCVA, proportion of cases with
      improvement of 1 or more lines of BSCVA, proportion of cases with BSCVA and
      uncorrected visual acuity (UCVA) 20/12.5 or better, proportion of cases with
      BSCVA and UCVA 20/16 or better (6 months, 88% vs 54%, P=.002), and predictability
      +/-1.00 D (6 months, 100% vs 67%, P<.001) were all significantly better in the
      TICL group than the PRK group at all time periods studied postoperatively.
      Similarly, contrast sensitivity, tested at both the 5% photopic level and the 25%
      mesopic level, was significantly better at all postoperative time points in the
      TICL group. Mean spherical equivalent refraction was closer to emmetropia (0.28+/
      0.41 vs 0.76+/-0.86, P=.005), and predictability +/-0.50 D and stability of
      manifest refraction (+/-0.50 D and +/-1.00 D) were significantly better in the
      TICL group at all postoperative visits through 6 months. Mean astigmatism
      correction at 6 months was not significantly different between the two groups
      (0.52+/-0.33 vs 0.46+/-0.35, P=.450). CONCLUSIONS: The TICL performed better than
      PRK in all measures of safety (BSCVA), efficacy (UCVA), predictability, and
      stability in this comparison, supporting the TICL as a viable alternative to
      existing refractive surgical treatments.

PMID- 18041239
TI  - The Kelman Duet phakic intraocular lens: 1-year results.
AB  - PURPOSE: To evaluate the efficacy and safety of the Kelman Duet phakic
      intraocular lens (PIOL) for correction of moderate and high myopia. METHODS:
      Kelman Duet PIOLs were implanted in 169 eyes of 110 patients with moderate or
      high myopia. In all cases, implantation of the lens was feasible through an
      incision of less than 2.5 mm without complications. Uncorrected visual acuity
      (UCVA), manifest refraction, best spectacle-corrected visual acuity (BSCVA),
      intraocular pressure, central corneal endothelial change, and complications were
      recorded preoperatively and during 12 months of follow-up. RESULTS: Following
      PIOL implantation, 23 (13.61%) eyes required LASIK retreatment for the correction
      of residual astigmatic refractive error and were excluded from the refractive
      analysis. Best spectacle-corrected visual acuity remained the same or improved in
      95.04% of eyes, 81.30% of eyes (100) were within +/-1.00 diopter (D) of
      emmetropia, and 57.72% (71) were within +/-0.50 D. Intraocular pressure increased
      slightly in the first 4 weeks postoperatively but stabilized to the preoperative
      level by 3 months. Mean endothelial cell loss at 12 months was 5.43%. Oval pupils
      developed in 10.1% of eyes. Haptic exchange or reposition was performed in 7.76%
      of cases. CONCLUSIONS: The Kelman Duet PIOL was safe and effective for the
      correction of moderate to high myopia in this study with 1-year follow-up and
      offered the advantage of using a 2.5-mm or less incision width. Accurate haptic
      sizing remains a challenge and haptic exchange to correct haptic size mismatching
      is possible.

PMID- 18041241
TI  - Central corneal thickness measurements in unoperated eyes and eyes after PRK for
      myopia using Pentacam, Orbscan II, and ultrasonic pachymetry.
AB  - PURPOSE: To compare central corneal thickness measurements obtained in unoperated
      eyes and eyes after myopic photorefractive keratectomy (PRK) using a rotating
      Scheimpflug camera (Pentacam), a scanning slit corneal topography system (Orbscan
      II), and ultrasonic pachymetry. METHODS: Corneal thickness was measured using
      Pentacam, Orbscan II, and ultrasonic pachymetry in 25 unoperated eyes (unoperated
      group), 24 eyes 1 to 3 months after myopic PRK (early postoperative PRK group),
      and 21 eyes 4 months or more after myopic PRK (late postoperative PRK group).
      RESULTS: In the unoperated group, corneal thickness measurements were similar for
      all three methods (P=.125). In the early postoperative PRK group, Orbscan
      measurements were thinner than Pentacam and ultrasonic measurements by a mean of
      69.4 microm and 63.4 microm (P<.001 and P=.002, respectively). In the late
      postoperative PRK group, Orbscan measurements were thinner than Pentacam
      measurements by a mean of 36.0 microm (P=.017). Pentacam and ultrasonic
      pachymetry measurements were similar for all three groups with a mean difference
      of approximately 10 microm. CONCLUSIONS: Following myopic PRK, Pentacam was
      comparable to ultrasonic pachymetry in measuring corneal thickness, whereas
      Orbscan measurements were thinner.

PMID- 18041240
TI  - Wavefront analysis comparison of LASIK outcomes with the femtosecond laser and
      mechanical microkeratomes.
AB  - PURPOSE: To evaluate differences related to ocular aberrations after customized
      LASIK for myopia using three different microkeratomes. METHODS: Charts of 410
      patients who underwent customized LASIK with the Alcon LADARVision4000 excimer
      laser were reviewed. Patients were stratified according to the device used to
      create the flap: Moria M2 microkeratome, Bausch & Lomb Hansatome microkeratome,
      or IntraLase laser. The difference between the wavefront pre- and postoperative
      value received a positive or a negative sign if the change occurred toward or
      away from zero, respectively, and it was compared to preoperative minus
      postoperative manifest refraction spherical equivalent (MRSE). RESULTS: Patients
      showed increase in the aberration level after LASIK with the three devices used
      in this study. IntraLase spherical aberration change tended to be better than
      mechanical microkeratomes for higher MRSE values (IntraLase compared to
      Hansatome, P < or = .023 for MRSE values > or = 4.00 diopters [D]; IntraLase
      compared to Moria, P < or = .015 for MRSE values > or = 2.00 D). For total
      aberrations, the improvement values for IntraLase tended to be higher than those
      for Moria (IntraLase compared to Moria, P < or = .021 for MRSE values > or = 3.00
      D). For total higher order aberrations, IntraLase values tended to be better than
      Moria and Hansatome microkeratomes (IntraLase compared to Hansatome, P < or =
      .047 for MRSE values between 3.00 and 8.00 D; IntraLase compared with Moria, P <
      or = .002 for MRSE values > or = 2.00 D). Change in coma root-mean-square was
      similar for the three groups. CONCLUSIONS: The findings suggest the femtosecond
      laser provides a better platform for LASIK than the commonly used microkeratomes
      analyzed in this study.

PMID- 18041242
TI  - Comparison of central corneal thickness measured with Orbscan and Pentacam.
AB  - PURPOSE: To compare central corneal thickness measurements obtained with Orbscan
      II using the acoustic equivalent correction factor (CF) and Pentacam in eyes
      screened for refractive surgery. METHODS: Central corneal thickness in 91 eyes of
      51 volunteers with a spherical equivalent refraction ranging from -17.00 to +5.50
      diopters (D) (mean: -3.75+/-4.19 D) was measured with both Orbscan II (CF) and
      Pentacam prior to refractive surgery. RESULTS: Central comeal thickness
      measurements ranged from 438 to 610 microm with Orbscan II (CF) and from 472 to
      634 microm with Pentacam. The differences between Pentacam and Orbscan II (CF)
      measurements ranged from -43 to +52 microm (mean: -13.98+/-14.79 microm); these
      differences were statistically significant (P<.0001). No correlation was found
      between the difference in central corneal thickness and refractive error.
      CONCLUSIONS: These results suggest measurements obtained with the Orbscan II (CF)
      are thinner than those obtained with the Pentacam. Further studies are needed to
      determine which instrument is more accurate in measuring central corneal
      thickness.

PMID- 18041243
TI  - Medennium posterior chamber phakic refractive lens to correct high myopia.
AB  - PURPOSE: To determine the efficacy and safety of phakic refractive lens
      implantation to correct high myopia. METHODS: In this prospective study, a phakic
      refractive lens was implanted in 90 myopic eyes in which refractive errors ranged
      from -6.00 to -20.00 diopters (D) and laser refractive surgery was
      contraindicated. Uncorrected visual acuity (UCVA) and best-spectacle corrected
      visual acuity (BSCVA), manifest and cycloplegic refractions, and intraocular
      pressure (IOP) were assessed during a 1-year follow-up period. Possible
      complications, including endothelial cell counts, were evaluated. RESULTS:
      Spherical equivalent refraction measurements revealed a significant change from
      the preoperative mean value of -11.90+/-5.00 D to 0.04+/-0.20 D 1 year
      postoperatively (P=.001). The UCVA and BSCVA significantly improved
      postoperatively (P=.001 and P=.01, respectively). Seventy-two (80%) eyes and 61
      (68%) eyes were within +/-1.00 D and +/-0.50 D of the target refraction,
      respectively. A significant increase in IOP was found at every postoperative
      visit (P=.01). There was a trend toward decreased endothelial cell density
      postoperatively, although the difference did not reach significance. No major
      complications were found during the 1-year follow-up period. CONCLUSIONS: The
      implantation of a phakic refractive lens seems to be a predictable and well
      tolerated procedure for correcting high myopia. Complications such as development
      of cataract, implant dislocation, decreases in endothelial cell counts, or
      development of glaucoma did not occur in this study.

PMID- 18041244
TI  - Conductive keratoplasty for presbyopia: 3-year results.
AB  - PURPOSE: To assess the long-term safety, efficacy, and stability of conductive
      keratoplasty (CK) in the treatment of presbyopia. METHODS: Ten near-plano
      presbyopic patients (6 women and 4 men) underwent unilateral CK with standard
      pressure technique in the non-dominant eye to improve their near vision. Mean age
      was 51+/-3.1 years (range: 46 to 56 years). Nine of the 10 patients were
      available for both 1- and 3-year follow-up examinations. RESULTS: Preoperative
      mean manifest refraction spherical equivalent (MRSE) was -0.17+/-0.29 diopters
      (D), yielding a mean near uncorrected visual acuity (UCVA) of J10. Three years
      after CK, the mean near UCVA was J3. The mean MRSE at 3 years was -1.06+/-0.81 D,
      which represents a 0.25 D change from the MRSE at 1 year. The MRSE in the
      dominant untreated eyes had a +0.26 D change during the 3-year period, which was
      not statistically different when compared to the CK-treated eyes during the 3
      year postoperative period. No eye lost best spectacle-corrected visual acuity or
      had induced cylinder > or =0.75 D. Seventy-eight percent had binocular distance
      UCVA 20/20 or better and near UCVA J3 or better. The average keratometry remained
      stable at 45.09 D 3 years postoperatively compared to 45.08 D 1 year
      postoperatively. CONCLUSIONS: Conductive keratoplasty for the treatment of
      presbyopia provided safe, effective, predictable, and stable results 3 years
      following the initial surgery. Refractive stability was similar for both the CK
      treated and untreated eyes with a small hyperopic shift noted during the 3-year
      follow-up period.

PMID- 18041245
TI  - Detection of cyclotorsional rotation during excimer laser ablation in LASIK.
AB  - PURPOSE: Positionally induced cyclotorsion could be an important factor in the
      correction of astigmatism during refractive surgery. We analyzed the change in
      cyclotorsional rotation during excimer laser ablation in LASIK surgery using the
      NIDEK Torsion Error Detector (TED). METHODS: One hundred ten patients (192 eyes)
      who underwent LASIK for myopic astigmatism, using the NIDEK Advanced Vision
      Excimer Laser (NAVEX) were measured for cyclotorsion during surgery using the TED
      system. The manifest refraction of these patients was -6.80+/-2.74 diopters (D)
      (range: -1.00 to -13.75 D). The iris pattern of the patient's eyes in the supine
      position was recorded via a CCD camera in the EC5000CXII excimer laser system,
      and it was compared to the iris pattern acquired during OPD-Scan measurement in
      the sitting position. RESULTS: During laser ablation, the degree of
      cyclotorsional rotation detected by TED was 1.33+/-1.88 degrees (range: -6.33 to
      2.99 degrees) clockwise and 1.00+/-1.79 degrees (range: -3.70 to 7.34 degrees)
      counterclockwise. The absolute degree of torsion error detected by the TED system
      was 2.33+/-1.16 degrees (range: 0 to 6.21 degrees). CONCLUSIONS: The
      effectiveness of the cylinder treatment can be reduced due to torsion errors. The
      degree of cyclotorsion constantly changes during laser ablation. Therefore, a
      monitoring system should be developed for the measurement of torsion error, and
      this will enable the maximum possible correction of the error during laser
      ablation.

PMID- 18041246
TI  - Corneal epithelial damage during LASIK: a review of 1873 eyes.
AB  - PURPOSE: To assess the incidence, risk factors, management, and sequelae of
      intraoperative epithelial damage during LASIK using a linearly advancing
      microkeratome. METHODS: Chart review of 1873 eyes (956 patients) that underwent
      primary LASIK using the Automated Corneal Shaper microkeratome and the VISX Star
      S2 excimer laser. The main outcome measure was the incidence of intraoperative
      epithelial damage (patch of loosened epithelium with or without any frank
      epithelial defect). Univariate and multivariate logistic regression were
      performed to identify risk factors for intraoperative epithelial damage. RESULTS:
      Intraoperative epithelial damage occurred in 31 (1.66%) of 1873 eyes. The
      incidence of intraoperative epithelial damage increased with increasing patient
      age (odds ratio [OR] 1.095/decade; 95% confidence interval [CI] 1.002 to 1.197,
      P=.045) and increasing years of contact lens wear (OR 1.136, 95% CI 1.024 to
      1.261, P=.016). No correlation was found for gender, corneal curvature, central
      corneal thickness, microkeratome plate depth, or preoperative or postoperative
      refraction. The risk of intraoperative epithelial damage was significantly higher
      in the second eye if damage occurred in the first eye (66.7% versus 0.67%, OR
      298.7, CI 78.2 to 1141.2, P<.001). Epithelial damage was managed successfully
      intraoperatively in all 31 eyes; recurrent corneal erosion was noted 4 months
      postoperatively in 1 eye but resolved after anterior stromal puncture.
      CONCLUSIONS: The risk for intraoperative epithelial damage during LASIK increases
      with patient age, years of contact lens wear, and intraoperative epithelial
      damage in the first eye during simultaneous bilateral LASIK, but with proper
      intraoperative management, postoperative sequelae are rare.

PMID- 18041247
TI  - Geometric customization of optical and transition zone parameters for treatment
      of compound myopic astigmatism with the NIDEK EC-5000 excimer laser.
AB  - PURPOSE: To compare the refractive outcome of two ablation zone designs using
      LASIK for the correction of compound myopic astigmatism. METHODS: This
      retrospective study compared refractive outcomes in two groups of patients
      undergoing LASIK. In the circular treatment group, 45 eyes were corrected with
      circular optical and transition zones of 6 mm and 6.5 mm, respectively. In the
      customized treatment group, 45 eyes were corrected with optical and transition
      zones enlarged along the flat axis to 6.5 mm and 7.5 mm, respectively. P values
      <.05 were considered statistically significant. RESULTS: Mean preoperative
      spherical equivalent refraction was -5.36+/-2.02 diopters (D) and -5.36+/- 2.13 D
      for the circular and customized treatment groups, respectively. Mean
      postoperative spherical equivalent refraction was -0.09+/-0.74 D and -0.11+/-0.42
      D for the circular and customized treatment groups, respectively. Mean cylinder
      was 0.49+/-0.39 D and 0.22+/-0.43 D for the circular and customized treatment
      groups, respectively (P<.001). Postoperative blur strength index was 0.68+/-0.44
      D and 0.39+/-0.27 D in the circular and customized treatment groups, respectively
      (P<.001). Uncorrected visual acuity was significantly better in the customized
      treatment group compared with the circular treatment group (P<.05). The gain in
      lines of best spectacle-corrected visual acuity was significantly greater in the
      customized treatment group compared with the circular treatment group (P<.001).
      CONCLUSIONS: An elliptical ablation zone for treating compound myopic astigmatism
      results in better efficacy, safety, and lower tissue removal than a circular
      treatment zone. This may be due to the geometric optimization provided by the
      enlargement of the optical and transition zones along the flat meridian.

PMID- 18041248
TI  - Intraoperative autorefraction for combined phakic intraocular lens explantation
      and cataract surgery.
AB  - PURPOSE: To evaluate intraoperative autorefraction during combined phakic
      intraocular lens (PIOL) explantation and cataract surgery. METHODS: Phakic
      intraocular lens explantation was followed by crystalline lens emulsification and
      reformation of the anterior chamber with balanced salt solution. Autorefraction
      was performed intraoperatively with the Nikon Retinomax 2, and the IOL power was
      calculated using a formula for myopic eyes: IOL for emmetropia = 1.3 x aphakic
      spherical equivalent refraction + 1.45. RESULTS: Nineteen myopic eyes of 15
      patients with anterior or posterior chamber PIOL (including 6 eyes that had
      undergone photorefractive keratectomy) were treated. Two months postoperatively,
      mean spherical equivalent refraction was -0.56+/-0.40 diopters (D) (range: 0 to 
      1.50 D). CONCLUSIONS: In myopic eyes, intraoperative auto-refraction provided a
      simple and reliable method to calculate IOL power in combined PIOL explantation
      and cataract surgery.

PMID- 18041249
TI  - Nine-year follow-up of a posterior chamber phakic IOL in one eye and LASIK in the
      fellow eye of the same patient.
AB  - PURPOSE: To compare the long-term results (9 years) of LASIK in one eye and
      phakic intraocular lens (implantable contact lens [ICL]) implantation in the
      fellow eye of the same patient. METHODS: A patient with high myopia underwent
      LASIK with a MEL 60 excimer laser in one eye (spherical equivalent refraction 
      9.75 diopters [D], 5-mm optical zone with no transition zone) and phakic
      intraocular lens (STAAR Collamer implantable contact lens [ICL]) implantation
      (spherical equivalent refraction -9.50 D) in the fellow eye. RESULTS: At 9 years
      postoperatively, the mean spherical equivalent refraction was -1.00 in the eye
      with the ICL and -1.75 D in the eye that underwent LASIK. During the first 6
      postoperative months in the LASIK eye, refraction regressed, but remained stable
      during the remainder of follow-up. Uncorrected visual acuity was 20/25 in the eye
      with the ICL and 20/30 in the LASIK eye, whereas best spectacle-corrected visual
      acuity was 20/20 in both eyes. Less night vision problems (glare and halos) were
      experienced in the eye with the ICL compared to the LASIK eye. Although the
      patient initially preferred the LASIK procedure, at last follow-up 9 years
      postoperatively, increased overall satisfaction was reported for the eye with the
      ICL compared to the LASIK eye. CONCLUSIONS: Nine years after treatment of high
      myopia with the ICL and LASIK in the same patient, better quality of vision,
      stability, and satisfaction score were achieved in the eye with the ICL compared
      to the eye that had undergone LASIK. No long-term sight-threatening complications
      were found during followup.

PMID- 18041250
TI  - Fifteen-year follow-up after LASIK: case report.
AB  - PURPOSE: To present 15-year follow-up of one of the first LASIK-treated patients.
      METHODS: A 40-year-old woman underwent LASIK in the left eye for myopia in July
      1991. RESULTS: Fifteen years after LASIK, spherical equivalent error was
      statistically significantly reduced from preoperative -8.75 -3.75 x 025 degrees
      to postoperative -4.25 -2.75 x 010 degrees. Six months postoperatively,
      refractive and topographic stability was obtained and remained stable during
      follow-up with no significant changes between interval mean time (-3.75 -3.00 x
      020 degrees 6 months postoperatively to -4.25 -2.75 x 010 degrees 15 years
      postoperatively). No early or late postoperative complications were observed, and
      confocal microscopy revealed a regenerated nerve plexus and normal cornea.
      However, increased scattering and presence of debris were observed at the flap
      interface even after 15 years. Despite moderate predictability (residual
      refractive error) and small optical zone, the patient was satisfied with final
      outcome. CONCLUSIONS: One of the first LASIK-treated patients was presented 15
      years after surgery. LASIK in this patient had low predictability, although
      refractive and topographic stability occurred after the sixth postoperative
      month. No long-term, sight-threatening complications were identified during
      follow-up.

PMID- 18041251
TI  - Bilateral keratectasia after photorefractive keratectomy.
AB  - PURPOSE: To report the clinical features, management, and outcome of a patient
      who developed bilateral ectasia after photorefractive keratectomy (PRK). METHODS:
      Case report of a 35-year-old man who underwent bilateral PRK. Preoperative
      uncorrected visual acuity was 20/200 in the right eye and 20/100 in the left eye.
      The patient's history was unremarkable and he denied a family history of ocular
      disorders. RESULTS: Two weeks after surgery, the patient presented with loss of
      visual acuity in both eyes. Uncorrected visual acuity was 20/80 in the right eye
      and 20/200 in the left eye. Objective refraction could not be obtained. Slit-lamp
      microscopy showed corneal thinning in both eyes. After examining the patient's
      family, his sister was found to have clinical and topographic keratoconus.
      CONCLUSIONS: Ectasia is a rare complication of PRK. We report the occurrence of
      bilateral ectasia after PRK in a patient with asymmetric bowtie topographies. We
      recommend that refractive surgery, even surface techniques such as PRK, be
      avoided in patients with a family history of keratoconus.

PMID- 18041252
TI  - Correcting highly aberrated eyes using large-stroke adaptive optics.
AB  - PURPOSE: To investigate the optical performance of a large-stroke deformable
      mirror in correcting large aberrations in highly aberrated eyes. METHODS: A large
      stroke deformable mirror (Mirao 52D; Imagine Eyes) and a Shack-Hartmann wavefront
      sensor were used in an adaptive optics system. Closed-loop correction of the
      static aberrations of a phase plate designed for an advanced keratoconic eye was
      performed for a 6-mm pupil. The same adaptive optics system was also used to
      correct the aberrations in one eye each of two moderate keratoconic and three
      normal human eyes for a 6-mm pupil. RESULTS: With closed-loop correction of the
      phase plate, the total root-mean-square (RMS) over a 6-mm pupil was reduced from
      3.54 to 0.04 microm in 30 to 40 iterations, corresponding to 3 to 4 seconds.
      Adaptive optics closed-loop correction reduced an average total RMS of 1.73+/
      0.998 to 0.10+/-0.017 microm (higher order RMS of 0.39+/-0.124 to 0.06+/-0.004
      microm) in the three normal eyes and 2.73+/-1.754 to 0.10+/-0.001 microm (higher
      order RMS of 1.82+/-1.058 to 0.05+/-0.017 microm) in the two keratoconic eyes.
      CONCLUSIONS: Aberrations in both normal and highly aberrated eyes were
      successfully corrected using the large-stroke deformable mirror to provide almost
      perfect optical quality. This mirror can be a powerful tool to assess the limit
      of visual performance achievable after correcting the aberrations, especially in
      eyes with abnormal corneal profiles.

PMID- 18041253
TI  - Effects of Zernike wavefront aberrations on visual acuity measured using
      electromagnetic adaptive optics technology.
AB  - PURPOSE: This study measured the changes in visual acuity induced by individual
      Zernike ocular aberrations of various root-mean-square (RMS) magnitudes. METHODS:
      A crx1 Adaptive Optics Visual Simulator (Imagine Eyes) was used to modify the
      wavefront aberrations in nine eyes. After measuring ocular aberrations, the
      device was programmed to compensate for the eye's wavefront error up to the 4th
      order and successively apply different individual Zernike aberrations using a 5
      mm pupil. The generated aberrations included defocus, astigmatism, coma, trefoil,
      and spherical aberration at a level of 0.1, 0.3, and 0.9 microm. Monocular visual
      acuity was assessed using computer-generated Landolt-C optotypes. RESULTS:
      Correction of the patients' aberrations improved visual acuity by a mean of 1
      line (-0.1 logMAR) compared to best sphero-cylinder correction. Aberrations of
      0.1 microm RMS resulted in a limited decrease in visual acuity (mean +0.05
      logMAR), whereas aberrations of 0.3 microm RMS induced significant visual acuity
      losses with a mean reduction of 1.5 lines (+0.15 logMAR). Larger aberrations of
      0.9 microm RMS resulted in greater visual acuity losses that were more pronounced
      with spherical aberration (+0.64 logMAR) and defocus (+0.62 logMAR), whereas
      trefoil (+0.22 logMAR) was found to be better tolerated. CONCLUSIONS: The
      electromagnetic adaptive optics visual simulator effectively corrected and
      generated wavefront aberrations up to the 4th order. Custom wavefront correction
      significantly improved visual acuity compared to best-spectacle correction.
      Symmetric aberrations (eg, defocus and spherical aberration) were more
      detrimental to visual performance.

PMID- 18041254
TI  - On-eye performance of custom wavefront-guided soft contact lenses in a habitual
      soft lens-wearing keratoconic patient.
AB  - PURPOSE: To assess visual, optical, and fitting characteristics for wavefront
      guided soft contact lenses produced for one habitual soft lens-wearing moderate
      keratoconic eye. METHODS: A process for production and evaluation of custom
      wavefront-guided soft contact lenses was developed. Wavefront aberrations were
      quantified with the COAS-HD wavefront sensor (Wavefront Sciences); soft contact
      lenses containing both high and low order aberrations were designed with custom
      software and produced using an ophthalmic lens lathe. Photopic high and low
      contrast logMAR visual acuity were recorded with the lens in place over an
      artificial 5-mm pupil and residual 2nd to 10th order root-mean-square (RMS)
      aberrations were analyzed over a 5-mm pupil. Comparisons were made to the eye's
      habitual toric soft contact lens using t tests. RESULTS: Photopic high contrast
      values for habitual and final custom contact lenses for a 5-mm pupil were 0.07+/
      0.06 and -0.08+/-0.05, respectively. Photopic low contrast values were 0.73+/
      0.06 and 0.62+/-0.07, respectively. Habitual and final custom correction low
      order RMS over a 5-mm pupil were 2.08 and 0.34 microm, and high order RMS levels
      were 0.77 and 0.39 microm, respectively. CONCLUSIONS: The final custom contact
      lens showed 1.5 lines of improvement for photopic high contrast (P=.03) and 1
      line for photopic low contrast (P=.11) over a 5-mm pupil compared to habitual
      correction. Low and high order aberrations were reduced by 84% and 50% over a 5
      mm pupil, respectively. Further improvements in performance of custom lenses may
      be achieved with further wavefront iterations.

PMID- 18041255
TI  - Analysis of the optical performance of presbyopia treatments with the defocus
      transfer function.
AB  - PURPOSE: A variety of techniques for treating presbyopia are available. However,
      these techniques are often disparate in the mechanisms used to cope with the lack
      of accommodation. Multizone-refractive, diffractive, and apodized intraocular
      lens technologies are currently being used. This article evaluates the optical
      performance of these markedly different technologies in a simple and comparable
      manner. METHODS: The Defocus Transfer Function is a mathematical technique for
      illustrating the Optical Transfer Function for all levels of defocus. By
      calculating the Defocus Transfer Function, the simulated performance of
      presbyopia correction technologies on distance, intermediate, and near vision can
      be evaluated simultaneously. Simulations of an opaque annular ring, a zonal
      refractive lens, a full-aperture diffractive lens, and an apodized diffractive
      lens are analyzed at pupil sizes of 3, 4, and 6 mm with this technique. RESULTS:
      The opaque annulus begins to act like a Fresnel amplitude zone plate for small
      pupils. The diffractive lens technologies had sharp optical performance at two
      distinct foci with a shift in performance from balanced to distance-biased for
      the apodized diffractive lens. The zonal refractive lens exhibited a multifocal
      effect. However, the optical performance of this technology fell below that of
      the diffractive lenses. CONCLUSIONS: The Defocus Transfer Function is a useful
      tool for analyzing presbyopia treatments. Different strategies for creating
      simultaneous vision or extended depth of field are easily compared. It may also
      be possible to reverse this technique to create an ideal pupil function that
      meets a desired multifocal performance specification.

PMID- 18041256
TI  - Astigmatic refraction using peaks of the interferogram Fourier transform for a
      Talbot Moire interferometer.
AB  - PURPOSE: To calculate the spectacle correction from a Talbot Moire wavefront
      sensor using the location of peaks in the Fourier transform of the interferogram
      image. METHODS: A relationship was developed between the spectacle correction for
      an ocular wavefront and the location of Fourier transform peaks in the aberrated
      interferogram. These spectral peaks were located to sub-pixel accuracy using a
      two-dimensional polynomial fit. A Talbot Moire wavefront system was developed to
      collect examination images from an astigmatic model eye and human eyes. The
      authors' Fourier transform calculation procedure was applied to captured
      interferogram and results were tabulated. RESULTS: Five examinations were made of
      the astigmatic model eye. The mean sphere and cylinder were -4.26 D (SD = 0.004)
      and -2.90 D (SD = 0.008), respectively. The axis for all measurements was 92
      degrees. These values were consistent with the model eye design parameters. The
      patient was a 46-year-old man with best spectacle-corrected visual acuity of
      20/20. Ten examinations were made of the patient's eye. The mean sphere and
      cylinder were -0.09 D (SD = 0.11) and -1.45 D (SD = 0.14), respectively. The mean
      axis was 69.1 degrees (SD = 1.29 degrees). The calculation time was 46 ms per
      image running on a 3.6-GHz PC using 512x512 fast Fourier transforms. This
      processing time is fast enough for real-time acquisition and display of a
      patient's refractive state. CONCLUSIONS: The Fourier transform calculations
      provided a fast and simple method of determining the spectacle correction in an
      aberrated ocular wavefront imaged by a Talbot Moire wavefront sensor.

PMID- 18041257
TI  - Stability of wavefront aberrations during the daytime after 6 months of overnight
      orthokeratology corneal reshaping.
AB  - PURPOSE: To evaluate the stability of wavefront aberrations during the daytime
      after 6 months of overnight orthokeratology corneal reshaping. METHODS: A
      prospective study of 26 eyes using the Ultravision BE lens design during 6 months
      of overnight wear. Uncorrected visual acuity (UCVA), cycloplegic refraction, and
      wavefront aberrometry were measured at 8 AM (within 1 hour after awakening and
      removing lenses), 1 PM (5 to 6 hours after lens removal), and 6 PM (10 to 12
      hours after lens removal). RESULTS: There was no significant difference in UCVA
      between 8 AM, 1 PM, and 6 PM (P=.383). Spherical power from wavefront aberrometry
      showed significant regression from 8 AM to 1 PM (P<.001) and stabilized near zero
      diopters. Total root-mean-square (RMS) increased and higher order aberration RMS
      and defocus (Z4) decreased between 8 AM and 1 PM (P<.001) but did not change for
      the rest of the day (P>.001). There was no statistically significant change in
      astigmatism (Z3 and Z5) (P=.449) and coma (Z7 and Z8) (P=.145) between 8 AM, 1
      PM, and 6 PM. Spherical aberration (Z12) showed regression throughout the day
      (P<.001). CONCLUSIONS: After 6 months of overnight orthokeratology wear, some
      optical aberrations showed regression during the day. Despite no significant
      change in UCVA during 10 to 12 hours, there was a significant increase in defocus
      (Z4) within the first 5 hours after removing the orthokeratology lens and a
      decrease in spherical aberration (Z12) throughout the day.

PMID- 18041258
TI  - Impact of an improved combination of signals from array coils in diffusion tensor
      imaging.
AB  - An improved method for the combination of signals from array coils is presented
      as a way to reduce the influence of the noise floor on the estimation of
      diffusion tensor imaging (DTI) parameters. By an optimized combination of signals
      from the array channels and complex averaging of measurements, this method leads
      to a significant reduction of the noise bias. This combination algorithm allows
      computation of accurate tensors by using the simple two point method and is shown
      to provide results similar to the ones obtained using the standard signal
      combination and a nonlinear regression method with noise parameter estimation. In
      many applications, the use of this combination method would result in a scan time
      reduction in comparison to the current standard. The effects of the improved
      combination on diffusion decay curves, fractional anisotropy maps, and apparent
      diffusion coefficient (ADC) profiles are demonstrated.

PMID- 18041259
TI  - Accuracy of q-space related parameters in MRI: simulations and phantom
      measurements.
AB  - The accuracy of q-space measurements was evaluated at a 3.0-T clinical magnetic
      resonance imaging (MRI) scanner, as compared with a 4.7-T nuclear magnetic
      resonance (NMR) spectrometer. Measurements were performed using a stimulated-echo
      pulse-sequence on n-decane as well as on polyethylene glycol (PEG) mixed with
      different concentrations of water, in order to obtain bi-exponential signal decay
      curves. The diffusion coefficients as well as the modelled diffusional kurtosis
      K(fit) were obtained from the signal decay curve, while the full-width at half
      maximum (FWHM) and the diffusional kurtosis K were obtained from the displacement
      distribution. Simulations of restricted diffusion, under conditions similar to
      those obtainable with a clinical MRI scanner, were carried out assuming various
      degrees of violation of the short gradient pulse (SGP) condition and of the long
      diffusion time limit. The results indicated that an MRI system can not be used
      for quantification of structural sizes less than about 10 microm by means of FWHM
      since the parameter underestimates the confinements due to violation of the SGP
      condition. However, FWHM can still be used as an important contrast parameter.
      The obtained kurtosis values were lower than expected from theory and the results
      showed that care must be taken when interpreting a kurtosis estimate deviating
      from zero.

PMID- 18041260
TI  - New perspectives on the sources of white matter DTI signal.
AB  - A minimalist numerical model of white matter is presented, the objective of which
      is to help provide a biological basis for improved diffusion tensor imaging (DTI)
      analysis. Water diffuses, relaxes, and exchanges in three compartments
      intracellular, extracellular, and myelin sheath. Exchange between compartments is
      defined so as to depend on the diffusion coefficients and the compartment sizes.
      Based on the model, it is proposed that an additive "baseline tensor" that
      correlates with intraaxonal water volume be included in the computation.
      Anisotropy and tortuosity calculated from such analysis may correspond better to
      tract ultrastructure than if calculated without the baseline. According to the
      model, reduced extracellular volume causes increased baseline and reduced
      apparent diffusion. Depending on the pulse sequence, reduced permeability can
      cause an increase in both the baseline and apparent diffusion.

PMID- 18041261
TI  - Simulations of short-time diffusivity in lung airspaces and implications for S/V
      measurements using hyperpolarized-gas MRI.
AB  - We demonstrate a method for simulating restricted diffusion of hyperpolarized
      gases in lung airspaces that does not rely on an idealized analytic model of
      alveolar structure. Instead, the restricting geometry was generated from digital
      representations of histological sections of actual lung tissue obtained from a
      rabbit model of emphysema. Monte-Carlo simulations of restricted diffusion were
      performed in the short-time-scale regime, for which the time-dependent
      diffusivity is quantitatively related to the surface-to-volume ratio (S/V) of the
      pore space. In each of the eight samples studied, the S/V extracted from the
      simulated time-dependent diffusivity curves differed by less than 3% from direct
      assessment of S/V using image-processing methods. Simulated MRI measurements of
      apparent diffusion coefficients (ADCs) were performed in three representative
      lung sections to determine the effect of realistic gradient pulse shapes on the
      extracted S/V values. It was confirmed that ADCs measured at short diffusion
      times using either narrow or square gradient pulses yield accurate S/V values
      based on previously derived theoretical relationships. Simulations of triangular
      and sinusoidal diffusion-sensitizing gradients were then used to quantify the
      modifications required to extract accurate S/V values from ADC measurements
      obtained using more realistic gradient waveforms.

PMID- 18041262
TI  - A unified computational framework for deconvolution to reconstruct multiple
      fibers from diffusion weighted MRI.
AB  - Diffusion magnetic resonance imaging (MRI) is a relatively new imaging modality
      which is capable of measuring the diffusion of water molecules in biological
      systems noninvasively. The measurements from diffusion MRI provide unique clues
      for extracting orientation information of brain white matter fibers and can be
      potentially used to infer the brain connectivity in vivo using tractography
      techniques. Diffusion tensor imaging (DTI), currently the most widely used
      technique, fails to extract multiple fiber orientations in regions with complex
      microstructure. In order to overcome this limitation of DTI, a variety of
      reconstruction algorithms have been introduced in the recent past. One of the key
      ingredients in several model-based approaches is deconvolution operation which is
      presented in a unified deconvolution framework in this paper. Additionally, some
      important computational issues in solving the deconvolution problem that are not
      addressed adequately in previous studies are described in detail here. Further,
      we investigate several deconvolution schemes towards achieving stable, sparse,
      and accurate solutions. Experimental results on both simulations and real data
      are presented. The comparisons empirically suggest that nonnegative least squares
      method is the technique of choice for the multifiber reconstruction problem in
      the presence of intravoxel orientational heterogeneity.

PMID- 18041263
TI  - Clinical DT-MRI estimation, smoothing, and fiber tracking with log-Euclidean
      metrics.
AB  - Diffusion tensor magnetic resonance imaging (DT-MRI or DTI) is an imaging
      modality that is gaining importance in clinical applications. However, in a
      clinical environment, data have to be acquired rapidly, often at the expense of
      the image quality. This often results in DTI datasets that are not suitable for
      complex postprocessing like fiber tracking. We propose a new variational
      framework to improve the estimation of DT-MRI in this clinical context. Most of
      the existing estimation methods rely on a log-Gaussian noise (Gaussian noise on
      the image logarithms), or a Gaussian noise, that do not reflect the Rician nature
      of the noise in MR images with a low signal-to-noise ratio (SNR). With these
      methods, the Rician noise induces a shrinking effect: the tensor volume is
      underestimated when other noise models are used for the estimation. In this
      paper, we propose a maximum likelihood strategy that fully exploits the
      assumption of a Rician noise. To further reduce the influence of the noise, we
      optimally exploit the spatial correlation by coupling the estimation with an
      anisotropic prior previously proposed on the spatial regularity of the tensor
      field itself, which results in a maximum a posteriori estimation. Optimizing such
      a nonlinear criterion requires adapted tools for tensor computing. We show that
      Riemannian metrics for tensors, and more specifically the log-Euclidean metrics,
      are a good candidate and that this criterion can be efficiently optimized.
      Experiments on synthetic data show that our method correctly handles the
      shrinking effect even with very low SNR, and that the positive definiteness of
      tensors is always ensured. Results on real clinical data demonstrate the
      truthfulness of the proposed approach and show promising improvements of fiber
      tracking in the brain and the spinal cord.

PMID- 18041264
TI  - Diffusion tensor analysis with invariant gradients and rotation tangents.
AB  - Guided by empirically established connections between clinically important tissue
      properties and diffusion tensor parameters, we introduce a framework for
      decomposing variations in diffusion tensors into changes in shape and
      orientation. Tensor shape and orientation both have three degrees-of-freedom,
      spanned by invariant gradients and rotation tangents, respectively. As an initial
      demonstration of the framework, we create a tunable measure of tensor difference
      that can selectively respond to shape and orientation. Second, to analyze the
      spatial gradient in a tensor volume (a third-order tensor), our framework
      generates edge strength measures that can discriminate between different
      neuroanatomical boundaries, as well as creating a novel detector of white matter
      tracts that are adjacent yet distinctly oriented. Finally, we apply the framework
      to decompose the fourth-order diffusion covariance tensor into individual and
      aggregate measures of shape and orientation covariance, including a direct
      approximation for the variance of tensor invariants such as fractional
      anisotropy.

PMID- 18041265
TI  - A computational framework for the statistical analysis of cardiac diffusion
      tensors: application to a small database of canine hearts.
AB  - We propose a unified computational framework to build a statistical atlas of the
      cardiac fiber architecture from diffusion tensor magnetic resonance images (DT
      MRIs). We apply this framework to a small database of nine ex vivo canine hearts.
      An average cardiac fiber architecture and a measure of its variability are
      computed using most recent advances in diffusion tensor statistics. This
      statistical analysis confirms the already established good stability of the fiber
      orientations and a higher variability of the laminar sheet orientations within a
      given species. The statistical comparison between the canine atlas and a standard
      human cardiac DT-MRI shows a better stability of the fiber orientations than
      their laminar sheet orientations between the two species. The proposed
      computational framework can be applied to larger databases of cardiac DT-MRIs
      from various species to better establish intraspecies and interspecies statistics
      on the anatomical structure of cardiac fibers. This information will be useful to
      guide the adjustment of average fiber models onto specific patients from in vivo
      anatomical imaging modalities.

PMID- 18041266
TI  - Probabilistic inference on Q-ball imaging data.
AB  - Diffusion-weighted magnetic resonance imaging MRI) and especially diffusion
      tensor imaging (DTI) have proven to be useful for the characterization of the
      microstructure of brain white matter structures in vivo. However, DTI suffers
      from a number of limitations in characterizing more complex situations. The most
      notable problem occurs when multiple fibre bundles are present within a voxel. In
      this paper, we have expanded the existing Q-ball imaging method to a Bayesian
      framework in order to fully characterize the uncertainty around the fibre
      directions, given the quality of the data. We have done this by using a recently
      proposed spherical harmonics decomposition of the diffusion-weighted signal and
      the resulting Q-ball orientation distribution function. Moreover, we have
      incorporated a model selection procedure which determines the appropriate
      smoothness of the orientation distribution function from the data. We show by
      simulation that our framework can indeed characterize the posterior probability
      of the fibre directions in cases with multiple fibre populations per voxel and
      have provided examples of the algorithm's performance on real data where this
      situation is known to occur.

PMID- 18041267
TI  - A fuzzy, nonparametric segmentation framework for DTI and MRI analysis: with
      applications to DTI-tract extraction.
AB  - This paper presents a novel fuzzy-segmentation method for diffusion tensor (DT)
      and magnetic resonance (MR) images. Typical fuzzy-segmentation schemes, e.g.,
      those based on fuzzy C means (FCM), incorporate Gaussian class models that are
      inherently biased towards ellipsoidal clusters characterized by a mean element
      and a covariance matrix. Tensors in fiber bundles, however, inherently lie on
      specific manifolds in Riemannian spaces. Unlike FCM-based schemes, the proposed
      method represents these manifolds using nonparametric data-driven statistical
      models. The paper describes a statistically-sound (consistent) technique for
      nonparametric modeling in Riemannian DT spaces. The proposed method produces an
      optimal fuzzy segmentation by maximizing a novel information-theoretic energy in
      a Markov-random-field framework. Results on synthetic and real, DT and MR images,
      show that the proposed method provides information about the uncertainties in the
      segmentation decisions, which stem from imaging artifacts including noise,
      partial voluming, and inhomogeneity. By enhancing the nonparametric model to
      capture the spatial continuity and structure of the fiber bundle, we exploit the
      framework to extract the cingulum fiber bundle. Typical tractography methods for
      tract delineation, incorporating thresholds on fractional anisotropy and fiber
      curvature to terminate tracking, can face serious problems arising from partial
      voluming and noise. For these reasons, tractography often fails to extract thin
      tracts with sharp changes in orientation, such as the cingulum. The results
      demonstrate that the proposed method extracts this structure significantly more
      accurately as compared to tractography.

PMID- 18041268
TI  - Tensor splines for interpolation and approximation of DT-MRI with applications to
      segmentation of isolated rat hippocampi.
AB  - In this paper, we present novel algorithms for statistically robust interpolation
      and approximation of diffusion tensors-which are symmetric positive definite
      (SPD) matrices-and use them in developing a significant extension to an existing
      probabilistic algorithm for scalar field segmentation, in order to segment
      diffusion tensor magnetic resonance imaging (DT-MRI) datasets. Using the
      Riemannian metric on the space of SPD matrices, we present a novel and robust
      higher order (cubic) continuous tensor product of B-splines algorithm to
      approximate the SPD diffusion tensor fields. The resulting approximations are
      appropriately dubbed tensor splines. Next, we segment the diffusion tensor field
      by jointly estimating the label (assigned to each voxel) field, which is modeled
      by a Gauss Markov measure field (GMMF) and the parameters of each smooth tensor
      spline model representing the labeled regions. Results of interpolation,
      approximation, and segmentation are presented for synthetic data and real
      diffusion tensor fields from an isolated rat hippocampus, along with validation.
      We also present comparisons of our algorithms with existing methods and show
      significantly improved results in the presence of noise as well as outliers.

PMID- 18041269
TI  - Representing diffusion MRI in 5-D simplifies regularization and segmentation of
      white matter tracts.
AB  - We present a new five-dimensional (5-D) space representation of diffusion
      magnetic resonance imaging (dMRI) of high angular resolution. This 5-D space is
      basically a non-Euclidean space of position and orientation in which crossing
      fiber tracts can be clearly disentangled, that cannot be separated in three
      dimensional position space. This new representation provides many possibilities
      for processing and analysis since classical methods for scalar images can be
      extended to higher dimensions even if the spaces are not Euclidean. In this
      paper, we show examples of how regularization and segmentation of dMRI is
      simplified with this new representation. The regularization is used with the
      purpose of denoising and but also to facilitate the segmentation task by using
      several scales, each scale representing a different level of resolution. We
      implement in five dimensions the Chan-Vese method combined with active contours
      without edges for the segmentation and the total variation functional for the
      regularization. The purpose of this paper is to explore the possibility of
      segmenting white matter structures directly as entirely separated bundles in this
      5-D space. We will present results from a synthetic model and results on real
      data of a human brain acquired with diffusion spectrum magnetic resonance imaging
      (MRI), one of the dMRI of high angular resolution available. These results will
      lead us to the conclusion that this new high-dimensional representation indeed
      simplifies the problem of segmentation and regularization.

PMID- 18041270
TI  - A probabilistic model-based approach to consistent white matter tract
      segmentation.
AB  - Since the invention of diffusion magnetic resonance imaging (dMRI), currently the
      only established method for studying white matter connectivity in a clinical
      environment, there has been a great deal of interest in the effects of various
      pathologies on the connectivity of the brain. As methods for in vivo tractography
      have been developed, it has become possible to track and segment specific white
      matter structures of interest for particular study. However, the consistency and
      reproducibility of tractography-based segmentation remain limited, and attempts
      to improve them have thus far typically involved the imposition of strong
      constraints on the tract reconstruction process itself. In this work we take a
      different approach, developing a formal probabilistic model for the relationships
      between comparable tracts in different scans, and then using it to choose a
      tract, a posteriori, which best matches a predefined reference tract for the
      structure of interest. We demonstrate that this method is able to significantly
      improve segmentation consistency without directly constraining the tractography
      algorithm.

PMID- 18041271
TI  - Automatic tractography segmentation using a high-dimensional white matter atlas.
AB  - We propose a new white matter atlas creation method that learns a model of the
      common white matter structures present in a group of subjects. We demonstrate
      that our atlas creation method, which is based on group spectral clustering of
      tractography, discovers structures corresponding to expected white matter anatomy
      such as the corpus callosum, uncinate fasciculus, cingulum bundles, arcuate
      fasciculus, and corona radiata. The white matter clusters are augmented with
      expert anatomical labels and stored in a new type of atlas that we call a high
      dimensional white matter atlas. We then show how to perform automatic
      segmentation of tractography from novel subjects by extending the spectral
      clustering solution, stored in the atlas, using the Nystrom method. We present
      results regarding the stability of our method and parameter choices. Finally we
      give results from an atlas creation and automatic segmentation experiment. We
      demonstrate that our automatic tractography segmentation identifies corresponding
      white matter regions across hemispheres and across subjects, enabling group
      comparison of white matter anatomy.

PMID- 18041272
TI  - Parsimonious model selection for tissue segmentation and classification
      applications: a study using simulated and experimental DTI data.
AB  - One aim of this work is to investigate the feasibility of using a hierarchy of
      models to describe diffusion tensor magnetic resonance (MR) data in fixed tissue.
      Parsimonious model selection criteria are used to choose among different models
      of diffusion within tissue. Using this information, we assess whether we can
      perform simultaneous tissue segmentation and classification. Both numerical
      phantoms and diffusion weighted imaging (DWI) data obtained from excised pig
      spinal cord are used to test and validate this model selection framework. Three
      hierarchical approaches are used for parsimonious model selection: the Schwarz
      criterion (SC), the F-test t-test (F- t), proposed by Hext, and the F-test F-test
      (F-F), adapted from Snedecor. The F - t approach is more robust than the others
      for selecting between isotropic and general anisotropic (full tensor) models.
      However, due to its high sensitivity to the variance estimate and bias in sorting
      eigenvalues, the F-F and SC are preferred for segmenting models with transverse
      isotropy (cylindrical symmetry). Additionally, the SC method is easier to
      implement than the F - t and F - F methods and has better performance. As such,
      this approach can be efficiently used for evaluating large MRI data sets. In
      addition, the proposed voxel-by-voxel segmentation framework is not susceptible
      to artifacts caused by the inhomogeneity of the variance in neighboring voxels
      with different degrees of anisotropy, which might contaminate segmentation
      results obtained with the techniques based on voxel averaging.

PMID- 18041273
TI  - High-dimensional spatial normalization of diffusion tensor images improves the
      detection of white matter differences: an example study using amyotrophic lateral
      sclerosis.
AB  - Spatial normalization of diffusion tensor images plays a key role in voxel-based
      analysis of white matter (WM) group differences. Currently, it has been achieved
      using low-dimensional registration methods in the large majority of clinical
      studies. This paper aims to motivate the use of high-dimensional normalization
      approaches by generating evidence of their impact on the findings of such
      studies. Using an ongoing amyotrophic lateral sclerosis (ALS) study, we evaluated
      three normalization methods representing the current range of available
      approaches: low-dimensional normalization using the fractional anisotropy (FA),
      high-dimensional normalization using the FA, and high-dimensional normalization
      using full tensor information. Each method was assessed in terms of its ability
      to detect significant differences between ALS patients and controls. Our findings
      suggest that inadequate normalization with low-dimensional approaches can result
      in insufficient removal of shape differences which in turn can confound FA
      differences in a complex manner, and that utilizing high-dimensional
      normalization can both significantly minimize the confounding effect of shape
      differences to FA differences and provide a more complete description of WM
      differences in terms of both size and tissue architecture differences. We also
      found that high-dimensional approaches, by leveraging full tensor features
      instead of tensor-derived indices, can further improve the alignment of WM
      tracts.

PMID- 18041274
TI  - Nonrigid coregistration of diffusion tensor images using a viscous fluid model
      and mutual information.
AB  - In this paper, a nonrigid coregistration algorithm based on a viscous fluid model
      is proposed that has been optimized for diffusion tensor images (DTI), in which
      image correspondence is measured by the mutual information criterion. Several
      coregistration strategies are introduced and evaluated both on simulated data and
      on brain intersubject DTI data. Two tensor reorientation methods have been
      incorporated and quantitatively evaluated. Simulation as well as experimental
      results show that the proposed viscous fluid model can provide a high
      coregistration accuracy, although the tensor reorientation was observed to be
      highly sensitive to the local deformation field. Nevertheless, this
      coregistration method has demonstrated to significantly improve spatial alignment
      compared to affine image matching.

PMID- 18041275
TI  - Linear models of cumulative distribution function for content-based medical image
      retrieval.
AB  - We propose an Image matching technique based on Cumulative Distribution Function,
      which provides a considerable reduction in the retrieval time. The two novel
      approaches called bit plane histogram and hierarchical bit plane histogram are
      discussed. Next, the image matching technique based on Cumulative Distribution
      Function is explained and a comparison of the various techniques is brought out.
      The CDF of the query and the images in the database are approximated by piecewise
      linear models with two parameters, slope and intercept at various grayscale
      intervals. The contiguous set of lines approximating the CDFs enables us to
      compare the query image and the images in the database with corresponding
      estimated slopes and intercepts. As the dynamic range of CDF is from 0 to 1,
      images of different sizes can be compared. Approximation of CDFs with lines
      further reduces the dimension of the image features and thus improves the speed
      of matching.

PMID- 18041276
TI  - Automated detection of anesthetic depth levels using chaotic features with
      artificial neural networks.
AB  - Monitoring the depth of anesthesia (DOA) during surgery is very important in
      order to avoid patients' interoperative awareness. Since the traditional methods
      of assessing DOA which involve monitoring the heart rate, pupil size, sweating
      etc, may vary from patient to patient depending on the type of surgery and the
      type of drug administered, modern methods based on electroencephalogram (EEG) are
      preferred. EEG being a nonlinear signal, it is appropriate to use nonlinear
      chaotic parameters to identify the anesthetic depth levels. This paper discusses
      an automated detection method of anesthetic depth levels based on EEG recordings
      using non-linear chaotic features and neural network classifiers. Three nonlinear
      parameters, namely, correlation dimension (CD), Lyapunov exponent (LE) and Hurst
      exponent (HE) are used as features and two neural network models, namely, multi
      layer perceptron network (feed forward model) and Elman network (feedback model)
      are used for classification. The neural network models are trained and tested
      with single and multiple features derived from chaotic parameters and the
      performances are evaluated in terms of sensitivity, specificity and overall
      accuracy. It is found from the experimental results that the Lyapunov exponent
      feature with Elman network yields an overall accuracy of 99% in detecting the
      anesthetic depth levels.

PMID- 18041277
TI  - A methodology for using simulation to optimize emergency mass vaccination
      parameters.
AB  - For any preparedness plan to be effective it must be put to test or verified.
      Simulation methodology shows high potential for studying disaster and mass
      vaccination preparedness. Unlike physical drills, simulation models are less
      expensive, take less time to be conducted, and are well suited for testing
      alternative solutions. The decision makers can modify and analyze the model in
      order to test and evaluate numerous scenarios and operating parameters. In this
      paper, we offer a systematic approach that can be used with simulation analysis
      by practitioners to develop operating decisions for emergency preparedness in
      general and mass vaccination clinics in particular. An actual mass vaccination
      center in a county health department of a southern state is used to illustrate
      the proposed methodology.

PMID- 18041278
TI  - Detection of obstructive respiratory abnormality using flow-volume spirometry and
      radial basis function neural networks.
AB  - In this work detection of pulmonary abnormalities carried out using flow-volume
      spirometer and Radial Basis Function Neural Network (RBFNN) is presented. The
      spirometric data were obtained from adult volunteers (N=100) with standard
      recording protocol. The pressure and resistance parameters were derived using the
      theoretical approximation of the activation function representing pressure-volume
      relationship of the lung. The pressure-time and resistance-expiration volume
      curves were obtained during maximum expiration. The derived values together with
      spirometric data were used for classification of normal and obstructive
      abnormality using RBFNN. The results revealed that the proposed method is useful
      for detecting the pulmonary functions into normal and obstructive conditions.
      RBFNN was found to be effective in differentiating the pulmonary data and it was
      confirmed by measuring accuracy, sensitivity, specificity and adjusted accuracy.
      As spirometry still remains central in the observations of pulmonary function
      abnormalities these studies seems to be clinically relevant.

PMID- 18041279
TI  - Wireless body sensor network using medical implant band.
AB  - A wireless body sensor network hardware has been designed and implemented based
      on MICS (Medical Implant Communication Service) band. The MICS band offers the
      advantage of miniaturized electronic devices that can either be used as an
      implanted node or as an external node. In this work, the prototype system uses
      temperature and pulse rate sensors on nodes. The sensor node can transmit data
      over the air to a remote central control unit (CCU) for further processing,
      monitoring and storage. The developed system offers medical staff to obtain
      patient's physiological data on demand basis via the Internet. Some preliminary
      performance data is presented in the paper.

PMID- 18041280
TI  - E-Nose system for anesthetic dose level detection using artificial neural
      network.
AB  - In this study, an E-Nose system was realized for the anesthetic dose level
      prediction. For this purpose, sevoflurane anesthetic agent was measured using the
      E-Nose system implemented with sensor array of quartz crystal microbalances
      (QCM). In surgeries, anesthetic agents are given to the patients with carrier
      gases of oxygen (02) and nitrous oxide (N20). Frequency changes on QCM sensors to
      the eight sevoflurane anesthetic dose levels were recorded via RS-232 serial
      port. A multilayer feed forward artificial neural network (MLNN) structure was
      used to provide the relationship between the frequency change and the anesthetic
      dose level. The MLNNs were trained with the measured data using Levenberg
      Marquardt algorithm. Then, the trained MLNNs were tested with random data. The
      results have showed that, acceptable anesthetic dose level predictions have been
      obtained successfully.

PMID- 18041281
TI  - The use of information technologies among rural and urban physicians in Florida.
AB  - This study examines rural urban differences in the use of various information
      technologies (IT) applications by physicians in the ambulatory setting. Findings
      suggest that no differences exist between rural and urban physicians with respect
      to the use of a computer (77.4 vs 81.4; p=.144) or with the availability of an
      Internet connection (95.0 vs 96.5; p=.249) in the office. However, rural
      physicians were significantly less likely than urban doctors to indicate using e
      mail with patients (7.9 vs 17.2%; p<.001) and slightly less likely to use a
      personal digital assistant (PDA) (32.3 vs 37.9; p=.091). Rural doctors were
      significantly less likely to indicate routinely using an electronic health
      records (EHR) system (17.6 vs 24.1; p=.020). EHR differences between rural and
      urban physicians were not significant (p=.124) in multivariate analyses and were
      explained away by practice size (p<.001) and practice type (p=.015). Most
      barriers to EHR did not differ between rural and urban physicians. However, rural
      physicians more commonly cited barriers associated with temporary disruptions to
      productivity or disruptions in access to records when computers systems fail. In
      sum, EHR use and patient e-mailing is less common in rural areas. While much of
      this variability can be explained by rural practice characteristics, these
      findings illustrate the need for further efforts to identify and alleviate
      barriers and encourage health IT adoption in rural areas.

PMID- 18041282
TI  - Exploring physician adoption of EMRs: a multi-case analysis.
AB  - The adoption of new technology within healthcare has been promoted as a way to
      reduce costs and increase efficiencies as well as improve quality. The literature
      has documented a significant number of implementation failures by large groups
      and hospitals with access to IT skills and resources. Given the low adoption rate
      among physicians, the challenges facing small practices can be daunting. While
      financial and technical barriers have been explored at the physician level, the
      actual implementation challenges facing small groups have not been explored. This
      paper presents a qualitative three case analysis of physician groups that have
      employed EMRs and the pre and post adoption insights. Results show that planning
      was a key common variable missing; the anticipated downtime was longer than
      expected and the workflow disruption and maintenance costs were underestimated.

PMID- 18041283
TI  - An evaluation of patients' opinions of primary care physicians: the use of
      EUROPEP in Gaza Strip-Palestine.
AB  - The objective of this paper is to identify the level of patients' satisfaction
      with primary care physicians. Data were gathered from an exit interview using a
      standardized questionnaire (EUROPEP) and background variables. A total of 956
      patients in fifteen primary health care clinics in Gaza Strip participated.
      Outcome measures is positive patient satisfaction (good and excellent ratings in
      the EUROPEP Index). As a results, the mean percentage of positive satisfaction
      with medical services was poor (41.8%). The poorest performance was recorded for:
      getting through to the clinic on the phone, being able to speak to physician on
      the telephone, time spent in waiting rooms and helping the patient deal with
      emotional problems. The comparison between clinical behaviour dimension and
      organization of care showed that clinical behaviour was evaluated higher. In
      conclusion, Palestinian patients expressed overall dissatisfaction with services
      provided by primary care physicians. These findings present a real challenge for
      Palestinian authority policy makers and administrators in terms of designing
      appropriate quality improvement strategies.

PMID- 18041284
TI  - Utilization and costs of medical services at military health facilities in
      Ibadan, Nigeria.
AB  - The Nigerian Army introduced user charges in its health care services in 1994.
      This study attempts to assess possible impact of user charges on the utilization
      of army health services in Ibadan, Nigeria. This is a descriptive, retrospective
      study and it involved the review of hospital records from 1992 to 1996 in
      military health facilities in Ibadan. Yearly consultation rate increased from 339
      per 1,000 population in 1992 to 581 per 1,000 population in 1996. While cost of
      care significantly increased over the years in the army health facilities,
      services were offered at lower costs when compared with the cost of similar
      services from non-military medical centers. Utilization of health services is not
      deterred in spite of the introduction of user charges. Further study was
      suggested to assess impact.

PMID- 18041285
TI  - A fuzzy logic-based decision support system on anesthetic depth control for
      helping anesthetists in surgeries.
AB  - In this study, a fuzzy logic-based anesthetic depth decision support system
      (ADDSS) was realized for anesthetic depth control to help anesthetists in
      surgeries. Depth of anesthesia for a patient can change according to anesthetic
      agent and characteristic properties of a patient such as age, weight, etc. During
      the surgery, depth of anesthesia of a patient is determined by the experience of
      anesthetist controlling of systolic arterial pressure (SAP) and heart pulse rate
      (HPR) parameters. Anesthetists could have tired and lost attention by inhaling of
      anesthetic gas leaks in long lasted operations. For that reason, improper
      anesthetic depth could be applied to the patients. So anesthesia could not be
      safety and comfortable. To remove this unwanted situation, an ADDSS was proposed
      for anesthetists. By the help of this system, precise anesthetic depth could have
      provided. Thus, the anesthetist will spend less time to provide anesthetic and
      the patient will have a safer and less expensive operation. This study was
      performed under sevoflurane anesthetic.

PMID- 18041286
TI  - The design of thermoelectric footwear heating system via fuzzy logic.
AB  - In this study, Heat Control of Thermoelectric Footwear System via Fuzzy Logic has
      been implemented in order to use efficiently in cold weather conditions.
      Temperature control is very important in domestic as well as in many industrial
      applications. The final product is seriously affected from the changes in
      temperature. So it is necessary to reach some desired temperature points quickly
      and avoid large overshoot. Here, fuzzy logic acts an important role. PIC 16F877
      microcontroller has been designed to act as fuzzy logic controller. The designed
      system provides energy saving and has better performance than proportional
      control that was implemented in the previous study. The designed system takes
      into consideration so appropriate parameters that it can also be applied to the
      people safely who has illnesses like diabetes, etc.

PMID- 18041287
TI  - Determining fractal dimension of umbilical artery Doppler signals using Hurst
      exponent.
AB  - Doppler signals from the umbilical artery of 20 women with normal pregnancy
      between 18 and 20 weeks of gestation were recorded. The AR spectral analysis
      method has been used to obtain the Doppler sonograms of umbilical artery
      belonging to normal pregnant subjects and fractal dimension curves were
      calculated using Hurst exponent. RI; PI and S/D indexes have been calculated from
      the maximum frequency envelope of Doppler sonograms and from the fractal
      dimension curve. Area under the curve from ROC curve for RI, PI and S/D indexes
      derived from maximum frequency waveform were calculated as 0.931, 0.959, 0.938,
      respectively and area under the curve for RI, PI and S/D indexes derived from
      fractal dimension curve were calculated as 0.933, 0.961, and 0.941, respectively.
      These results show that, the Doppler indexes derived from fractal dimension curve
      are as sensitive as Doppler indexes derived from maximum velocity curve. Power
      Spectral Density graphics were derived from Doppler signals and Hurst exponent
      values calculated to evaluate the blood flow changing during pregnancy. ROC curve
      for PSD(HURST) index was calculated as 0.97. According to this result, PSD(HURST)
      index is more sensitive to detect the blood flow changing than traditional
      Doppler indexes.

PMID- 18041288
TI  - A Tablet-PC application for the individual family service plan (IFSP).
AB  - Approximately 2% of children from birth through 2 years of age were identified as
      having disabilities in 2000. To provide effective intervention services to each
      child is important. Children with disabilities from birth to 3 years of age who
      receive early intervention services have an Individualized Family Service Plan
      (IFSP). In some community early intervention programs, IFSP data are collected
      and stored in paper-based format, making it difficult to retrieve information in
      an efficient manner. Information technology strategies could address these
      problems, thus enhancing the efficiency of the information management. This paper
      discusses a user requirement analysis, design and development of a Tablet-PC
      computer application for collecting IFSP data for young children in Milwaukee,
      Wisconsin. An early prototype for the Tablet-PC computer application for the IFSP
      was successfully developed and a preliminarily evaluation was conducted at two
      early intervention programs.

PMID- 18041289
TI  - Closing emergency operating rooms improves efficiency.
AB  - Long waiting times for emergency operations increase a patient's risk of
      postoperative complications and morbidity. Reserving Operating Room (OR) capacity
      is a common technique to maximize the responsiveness of an OR in case of arrival
      of an emergency patient. This study determines the best way to reserve OR time
      for emergency surgery. In this study two approaches of reserving capacity were
      compared: (1) concentrating all reserved OR capacity in dedicated emergency ORs,
      and (2) evenly reserving capacity in all elective ORs. By using a discrete event
      simulation model the real situation was modelled. Main outcome measures were: (1)
      waiting time, (2) staff overtime, and (3) OR utilisation were evaluated for the
      two approaches. Results indicated that the policy of reserving capacity for
      emergency surgery in all elective ORs led to an improvement in waiting times for
      emergency surgery from 74 (+/-4.4) minutes to 8 (+/-0.5) min. Working in overtime
      was reduced by 20%, and overall OR utilisation can increase by around 3%.
      Emergency patients are operated upon more efficiently on elective Operating Rooms
      instead of a dedicated Emergency OR. The results of this study led to closing of
      the Emergency OR in the Erasmus MC (Rotterdam, The Netherlands).

PMID- 18041290
TI  - Backpropagation ANN-based prediction of exertional heat illness.
AB  - Exertional heat illness is primarily a multi-system disorder results from the
      combined effect of exertional and thermoregulation stress. The severity of
      exertional heat illness can be classified as mild, intermediate and severe from
      non-specific symptoms like thirst, myalgia, poor concentration, hysteria,
      vomiting, weakness, cramps, impaired judgement, headache, diarrhea, fatigue,
      hyperventilation, anxiety, and nausea to more severe symptoms like exertional
      dehydration, heat cramps, heat exhaustion, heat injury, heatstroke,
      rhabdomyolysis, and acute renal failure. At its early stage, it is quite
      difficult to find out the severity of disease with manual screening because of
      overlapping of symptoms. Therefore, one need to classify automatically the
      disease based on symptoms. The 7:10:1 backpropagation artificial neural network
      model has been used to predict the clinical outcome from the symptoms that are
      routinely available to clinicians. The model has found to be effective in
      differentiating the different stages of exertional heat-illness with an overall
      performance of 100%.

PMID- 18041291
TI  - A study of the web as DTC drug marketing agent.
AB  - The growth of direct-to-consumer (DTC) marketing of pharmaceuticals in the USA
      has spawned the generation of web sites for consumer information and discussion,
      related to specific medical conditions and the efficacy of specific drugs. In
      such an environment consumers often find and act upon health information of
      variable quality, with little input from health professionals. Some health policy
      analysts argue that the emergence of such consumer "drug networks" will lead to
      unnecessary expenditure of money on prescription drugs, as consumers see ads and
      then demand that their providers prescribe that drug. Others say that an
      intelligent consumer will be able to research the information and narrow down a
      drug that will likely work for them personally, rather than having the provider
      "experiment" with different medications. There exist few cross-disciplinary
      evaluative frameworks for assessing such health information, especially within
      commercial search engines. This study serves as an exploratory technology
      assessment that examines the prevalence of web-based DTC for a popular
      prescription drug and the impact on healthcare consumers.

PMID- 18041292
TI  - Why there can be no sustainable national healthcare IT program without a
      translational health information science.
AB  - Health information technology research has historically suffered from the
      persistence of paper-based systems as a barrier to research and refinement of
      information models. While the field of (non-medical) information science offers a
      potentially rich source of data, there exist relatively few theoretical links
      between medical and non-medical information models. This paper argues that the
      establishment of an integrated translational research pathway is not only useful,
      but is a critical and necessary step in the realization of a national health
      information infrastructure in the USA.

PMID- 18041293
TI  - Assessment of in vitro antimalarial interactions between dihydroartemisinin and
      fosmidomycin.
AB  - Malaria remains one of the leading causes of morbidity and mortality in the
      tropics with an annual estimate of 500 million clinical cases and 2 million
      deaths. The treatment and control of malaria is becoming increasingly difficult
      due to Plasmodium falciparum resistance to commonly used antimalarials.
      Combination therapy is currently the strategy for combating multi-drug resistant
      falciparum malaria, through exploiting pharmacodynamic synergistic effects and
      delaying the emergence of drug resistance. The combination of artemisinin
      derivatives with fosmidomycin, which have different modes of action, appears to
      be one of the most promising combinations. The objective of the present study was
      to investigate the antimalarial interactions between dihydroartemisinin and
      fosmidomycin in vitro, against chloroquine-resistant (K1) and chloroquine
      sensitive (G112) P. falciparum strains. Concentration-response analysis was
      performed based on an in vitro schizont maturation inhibition test. The fixed
      concentration ratios of dihydroartemisinin: fosmidomycin used were 0:5,000,
      2:4,500, 6:3,500, 10:2,500, 14:1,500, 18:500 and 20:0 nM. The highest final
      concentrations of dihydroartemisinin and fosmidomycin were 20 and 5,000 nM,
      respectively. Results showed IC50 (drug concentration which produced 50% schizont
      maturation inhibition) medians (range) for dihydroartemisinin against K1 and G112
      strains to be 1.6 (1.2-2.0) and 2.5 (2.4-2.6) nM, respectively. The IC50 medians
      (range) for fosmidomycin against K1 and G112 strains were 1,347 (1,068-1,625) and
      786 (737-834) nM, respectively. An isobologram revealed an increasing trend for
      the fraction IC50 (FIC), which indicates marked antagonism of this drug
      combination against both chloroquine resistant and chloroquine sensitive strains.

PMID- 18041294
TI  - Cystic echinococcosis in Thailand with a special note on detection by serology in
      one family.
AB  - Thailand is a nonendemic area of echinococcosis. We report, herein, 3 cases with
      a special note on the use of serology in detection of the disease in one family.
      All cases were Thais. The first case was a man, having a cystic mass in the
      liver. He was subsequently diagnosed as having echinococcosis following positive
      serology. The second case, a male, had a renal hydatid cyst revealed by
      histopathology, and a positive serological test. The third case, a wife of case
      2, was positive by serological screening for echinococcosis and subsequently
      proven to have splenic and liver echinococcal cysts. The present findings support
      the use of serology in the case detection of echinococcosis in Thailand.

PMID- 18041295
TI  - Predatory efficiency of the sewage drain inhabiting larvae of Toxorhynchites
      splendens Wiedemann on Culex quinquefasciatus Say and Armigeres subalbatus
      (Coquillett) larvae.
AB  - The rate of predation by stage IV instar Toxorhynchites splendens larvae on the
      equivalent instar stage larvae of Culex quinquefasciatus and Armigeres
      subalbatus, co-occurring in sewage drains, were noted for a period of three
      consecutive days in the laboratory using different prey densities and
      combinations. The rate of predation varied by age of the predator, density of
      prey, and prey type. The number of Ar. subalbatus larvae consumed by a single Tx.
      splendens larva ranged between 0.50 +/- 0.71 and 16.40 +/- 2.01; while for Cx.
      quinquefasciatus larvae, the number consumed ranged from 0.20 +/- 0.42 to 20.40
      +/- 1.43 per day. The pupation rates of the prey species varied in respect to
      control, with a minimum of 0.20 +/- 0.42 pupa/day to a maximum of 12.20 +/- 2.30
      pupa/day in the presence of Tx. splendens. The values for the controls were 1.00
      +/- 0.87 and 14.44 +/- 2.83 pupa/day, respectively. Irrespective of prey
      densities and combinations, a single Tx. splendens fourth instar larvae was found
      to consume on average 10.07 larvae on the first day 16.57 larvae on the second
      day and 4.38 larvae on the third day, killing a total of 17.70 to 45.10 larvae,
      in three days. In the presence of Tx. splendens, the cumulative pupation,
      irrespective of prey, remained between 12.20 and 45.10, and differed
      significantly from control where the values were between 13.90 and 54.70. The
      results indicate that Tx. splendens can significantly reduce immature numbers and
      lower the rate of pupation of Cx. quinquefasciatus and Ar. subalbatus. Tx.
      splendens may be a potential biological resource in the control of mosquitoes
      inhabiting sewage drains.

PMID- 18041296
TI  - Cutaneous allergic vasculitis due to Solenopsis geminata (Hymenoptera:
      Formicidae) envenomation in Indonesia.
AB  - Severe cutaneous allergic vasculitis in a 60 year-old Caucasian male following
      the bite of the tropical fire ant, Solenopsis geminata (F.) is reported. Over the
      course of 8 weeks, the pathology progressed from an extensive red papular
      urticaria to vasculitis with peri-vascular inflammation and ulceration of the
      skin on the feet, ankles and lower limbs. Many of the affected areas of the skin
      eventually became covered with black eschar associated with further tissue
      breakdown and ulcer formation. After debridement, compression dressings,
      antimicrobial ointment and corticosteroids, complete healing eventually took
      place with only residual scarring. An awareness of the severe dermatologic
      reactions caused by a bite of S. geminata, albeit rare, is clinically important.
      Recognizing the characteristic skin lesions caused by the bite of S. geminata,
      treated with prompt administration of appropriate chemotherapy will speed
      recuperation of the patient and reduce possible secondary complications.

PMID- 18041298
TI  - Evaluation of a practical method to assess antiretroviral adherence in HIV
      infected Thai children.
AB  - The objective of this study was to evaluate a practical method to assess
      adherence to antiretroviral therapy by observing virological and immunological
      responses. We conducted a 12-month longitudinal cohort study of 162 HIV-infected
      Thai children. Adherence was assessed using 5 methods (self reporting calendar,
      records of missed doses, pill counts, physician assessment, and an interview
      questionnaire). CD4 count, percentage and viral load were performed at baseline
      and at 12 months. Mean adherence rates at 2, 6, and 12 months were 98, 100, and
      99% by the calendar method; 98, 100, and 100% by recording missed doses; 96, 96,
      and 92% by pill count; and 90, 94, and 97% by physician assessment. Poor
      agreement (kappa < or = 0.1) was found among the methods. There was a
      statistically significant difference (p = 0.05) in virological response between
      participants with > or = 95% adherence (0.8 log10) and those with < 95% adherence
      (0.2 log10) when pill counts were used to assess adherence. In conclusion,
      despite poor agreement among these tools, a pill count appeared to be the only
      practical, validated method to differentiate the virological outcome between
      those who were fully and partially adhere to the treatment regimen.

PMID- 18041299
TI  - Prevalence of human cytomegalovirus (HCMV) gB genotypes in Thai patients.
AB  - Human cytomegalovirus (HCMV) infection can cause asymptomatic to symptomic
      diseases leading to morbidity and mortality especially in immunocompromized
      patients. One factor of the difference in clinical outcome is the distinction of
      HCMV strain. As HCMV glycoprotein (g)B plays an important role in viral entry and
      neutralizing antibody induction, HCMV gB genotypes were determined in 161
      clinical specimens containing HCMV-DNA obtained from patients at King
      Chulalongkorn Memorial Hospital, Bangkok, Thailand during the year 2000 and 2004.
      Of the 113 (70%) samples that were able to be genotyped, mixed gB genotype was
      demonstrated in 35%, followed by gB1 (33%), gB3 (15%), gB2 (11%), and untyped
      (7%); gB4 was not detected. The distribution of HCMV gB genotypes between genders
      was not significantly different. Mixed gB genotype (35%) was found in HIV-
      infected patients.

PMID- 18041300
TI  - Effectiveness of influenza vaccination in prevention of influenza-like illness
      among inhabitants of old folk homes.
AB  - The aims of the study were to determine the attack rate of influenza-like illness
      among inhabitants of five old folk homes nationwide using influenza vaccine as a
      probe and the effectiveness of influenza vaccination in prevention of influenza
      like illness. We conducted a nonrandomized, single-blind placebo control study
      from June 2003 to February 2004. VAXIGRIP(R) 2003 Southern hemisphere formulation
      was used. Among 527 subjects, the attack rates of influenza-like illness in the
      influenza vaccine group were 6.4, 4.6 and 2.4% during the first, second and third
      2-month periods, respectively. The attack rates of influenza-like illness in the
      placebo group were 17.7, 13.8 and 10.1%. Influenza vaccination reduced the risk
      of contracting influenza-like illness by between 14, and 45%. The vaccine
      effectiveness in reducing the occurrence of influenza-like illness ranged from 55
      to 76%, during the 6-month study followup. The presence of cerebrovascular
      diseases significantly increased the risk of influenza-like illness (p < 0.005).
      Vaccine recipients had fewer episodes of fever, cough, muscle aches, runny nose
      (p < 0.001) and experience fewer sick days due to respiratory illness. Subjects
      who received influenza vaccination had clinically and statistically significant
      reductions in the attack rate of influenza-like illness. Our data support
      influenza vaccination of persons with chronic diseases and >50 year olds living
      in institutions.

PMID- 18041301
TI  - Efficacy of pulsed dyed laser (585 nm) in the treatment of molluscum contagiosum
      subtype 1.
AB  - Molluscum contagiosum is a common cutaneous disease that may be difficult to
      treat when there are multiple lesions; especially in children. This study was
      conducted to determine the efficacy of pulsed dye laser (585 nm) in the treatment
      of molluscum contagiosum in 20 children. In the treated group, 70.5% of lesions
      healed after the first treatment; the remaining 10.6% after the second treatment
      (2 weeks later). The overall cure rate was significantly different from the
      control group (p< 0.01). The therapy was also well tolerated. Only mild transient
      hypopigmentation and erythema were observed. None encountered infectious events.
      In conclusion, pulsed dye laser is a good alternative treatment for molluscum
      contagiosum due to high efficacy and mild transient side effects.

PMID- 18041297
TI  - Surveillance of subtype and genetic variation of the circulating strains of HIV-1
      in Thailand.
AB  - Two HIV-1 strains, CRF01_AE and subtype B', were reported in Thailand during the
      early years of the epidemic. Recently, an intersubtype recombination of HIV-1
      strain was found in Thailand. Eight-hundred and twenty-eight samples collected
      during years 1995-2004 from high-risk groups in Bangkok, northern, northeastern,
      and southern region of Thailand were studied. HIV-1 env nucleotide sequences were
      used for phylogenetic analysis of the circulating HIV-1 strain. By single HIV-1
      region (env) genotyping, CRFO1_AE was found in 97.3% and HIV-1 subtype B was
      found in 2.7%. A predominance of CRF01_AE was found in all geographic regions.
      Parallel analysis of the HIV-1 gag and env genes demonstrated that 2.1% and 4.0%
      of recombinant HIV-1 strains were found using p17 and p24 region sequences,
      respectively. The recombinant gag gene was also found in one southern isolate.
      Phylogenetic analysis of HIV-1 isolated from 20 provinces in 2002 suggested the
      northern and northeastern isolates were more related than the southern isolates
      which had the lowest genetic diversity of 0.13. The GPGQ V3 loop tip was also
      present in isolates from all regions. The molecular epidemiological data from
      this study may be useful for surveillance design as well as targeting prevention
      efforts. It also provides information regarding new antigenic regions of
      circulating strains responsible for the HIV-1 epidemic in Thailand.

PMID- 18041302
TI  - Occurrence of qacE/qacEDelta1 genes and their correlation with class 1 integrons
      in salmonella enterica isolates from poultry and swine.
AB  - In this study, a total of 122 Salmonella enterica isolates from poultry and swine
      were assessed for susceptibility to clinically important antibiotics and to
      benzalkonium chloride (BKC). All isolates were examined for the presence of the
      antiseptic resistance genes qacE and qacEDelta1 and intl1 (class 1 integrase).
      The intl1-positive strains were further investigated for the presence of the 3'
      conserved region. The results demonstrated widespread distribution of qacEDelta1
      (27%) but no isolate with qacE was observed. The intl1 gene was identified in 23
      isolates (70%) with qacEDelta1. All of the intl1-postive strains carried
      qacEDelta1 in 3' conserved segment, confirming that the qacEDelta1 gene is linked
      to the integrons. Increased MIC value to BKC was independent of the presence of
      qacEDelta1, and multiple antibiotic-resistant bacteria were no more tolerant to
      BKC than the non-multidrugresistant strains, regardless of the presence of
      qacEDelta1.

PMID- 18041303
TI  - Changing patterns of antimicrobial susceptibility of Shigella serotypes isolated
      from children with acute diarrhea in Manipal, South India, a 5 year study.
AB  - This study was carried out to determine the current pattern of Shigella
      serogroups and their antimicrobial resistance in children with acute
      gastroenteritis in Manipal, South India. A total of 1,200 stool samples were
      collected from April 2001 to May 2006 in children suffering from acute
      gastroenteritis attending the out-patient department of pediatrics at Kasturba
      Hospital, Manipal, South India. These samples were cultured for enteric
      pathogens. The isolates were confirmed to be Shigella by biochemical reactions
      and slide agglutination tests using specific antisera. Antimicrobial
      susceptibility was performed using an agar diffusion technique method following
      the National Committee for Clinical Laboratory Standard guidelines. Of 1,200
      stool samples, 68 (5.6%) were positive for Shigella spp, 31 (45%) were Shigella
      flexneri followed by S. sonnei in 20 (31%), S. boydii in 10 (15%), and S.
      dysenteriae in 6 (8%). Of the 68 isolates, 58 (85.7%) showed resistance to
      various drugs and 47 (70%) were resistant to two or more drugs. Resistance to
      trimethoprim-sulfmethoxazole, tetracycline, nalidixic acid and ampicillin was
      observed in this study. All the strains were resistant to nalidixic acid (100%)
      but sensitive to cefotaxime and ceftriaxone.

PMID- 18041304
TI  - Aeromonas hydrophila wound infection following a tiger bite in Nepal.
AB  - Aeromonas hydrophila is a rare human pathogen. Reports of zoonotic infection
      developing after large feline bites are even rarer. We are documenting the first
      case of human wound infection with A. hydrophila following a tiger bite. The
      patient responded well following wound debridement, secondary suturing and
      combination antibiotic therapy.

PMID- 18041305
TI  - Examination of diarrheal stools in Hat Yai City, South Thailand, for Escherichia
      coli O157 and other diarrheagenic Escherichia coli using immunomagnetic
      separation and PCR method.
AB  - A total of 493 stool samples from diarrheal patients in Songklanagarind Hospital,
      in southern Thailand, were examined for Escherichia coli O157 by the culture
      method combined with an immunomagnetic separation (IMS) technique. E. coli O157
      was not found, although the IMS-based method could detect 10(2)-10(3) CFU of
      artificially inoculated O157/g of stool samples. Polymerase chain reaction was
      also used for the detection and identification of diarrheagenic E coli from 530
      stool samples. The target genes were eae for enteropathogenic E. coli (EPEC), stx
      for enterohemorrhagic E. coli (EHEC), elt and est for enterotoxigenic E. coli
      (ETEC), ipaH for enteroinvasive E. coli (EIEC), and aggR for enteroaggregative E.
      coli (EAggEC). Fifty-eight diarrheagenic E. coli strains were detected in 55
      stool samples (10%) from 32 children and 23 adults. These included 31 EAggEC
      strains (5.8%), 13 ETEC strains (2.5%), 13 EPEC strains (2.5%), and one EIEC
      strain (0.2%). EHEC was not detected. The diarrheagenic E. coli strains were
      found mainly in children under 2 years of age (24 of 32 children). EAggEC strains
      and ETEC strains were susceptible to several antibiotics whereas the EPEC strains
      exhibited resistance to these antibiotics.

PMID- 18041306
TI  - Detection of VacA gene specific for Helicobactor pylori in hepatocellular
      carcinoma and cholangiocarcinoma specimens of Thai patients.
AB  - In order to investigate and compare the presence of Helicobacter pylori VacA in
      primary liver cancer specimens (12 hepatocellular carcinoma and 6
      cholangiocarcinoma) and control liver specimens (7 non-primary liver cancer) from
      Thai patients who underwent liver resection, H. pylori VacA gene was assayed in
      extracted DNA by real-time polymerase chain reaction. The selected amplicons
      revealed high homology compared with H. pylori VacA sequence. H. pylori VacA gene
      was detected in all primary liver cancer specimens and in 71% (5/7) of control
      liver specimens.

PMID- 18041307
TI  - Roseomonas gilardii subsp rosea, a pink bacterium associated with bacteremia: the
      first case in Thailand.
AB  - Roseomonas is a pink-pigmented, non-fermentative, gram-negative coccobacillus
      bacterium. Human infections caused by Roseomonas are very rare. We report the
      first case of bacteremia associated with Roseomonas gilardii subsp rosea in
      Thailand. The bacterium was isolated from blood culture and identified by
      cellular morphology, characteristics of colonies on blood agar, extensive
      biochemical tests and 16S ribosomal DNA sequencing.

PMID- 18041308
TI  - Sensitive detection of Pneumocystis jirovecii DNA in gastric wash using nested
      polymerase chain reaction.
AB  - One hundred and five samples of gastric washes were obtained from 52 pediatric
      patients. Eleven of the 105 samples (10%) gave positive results using
      immunofluorescence antibody test (IFA) for Pneumocystis jirovecii. Single-step
      polymerase chain reaction (PCR) produced 13% (14 samples), whereas detection by
      nested PCR was increased to 65 samples (62%). Moderate agreement (kappa = 0.5)
      was found between test results of IFA and single-step PCR, but no agreement was
      found between the results of IFA and nested PCR (kappa = 0.1).

PMID- 18041309
TI  - Role of interleukin-3 and signaling pathways on beta-thalassemia/HbE erythroid
      progenitor cell in culture.
AB  - In order to study the role of the cytokine interleukin-3 (IL-3) and its signaling
      pathways in erythropoiesis of beta-thalassemia/HbE erythroid progenitor cells,
      CD34 positive cells were isolated from peripheral blood of patients and healthy
      subjects. After culturing the cells in the presence or absence of IL-3, cell
      viability was measured by trypan blue staining and apoptotic cells were analyzed
      by flow cytometry. After 7 days of culture the highest percent erythroid
      progenitor cell viability was obtained with cells from healthy subjects, while
      the lowest percentage was found in those from splenectomized beta
      thalassemia/HbE. Viability of beta-thalassemia/HbE erythroid progenitor cells in
      the presence of IL-3 was higher than that of nonsupplemented cells. In addition,
      specific inhibitors of protein kinase C (Ro-318220), phospholipase C (U-73122)
      and Janus kinase 2 (AG-490) were used to investigate the involvement of signaling
      pathways in erythropoiesis. Percent apoptosis of erythroid progenitor cells from
      splenectomized beta-thalassemia/HbE subjects treated with RO-318220 was higher
      than those of nonsplenectomized beta-thalassemia/HbE and healthy subjects.
      Treatment with U-73122 resulted in enhanced percent apoptotic cells from normal
      and beta-thalassemia/HbE subjects. All these effects were independent of IL-3
      treatment.

PMID- 18041310
TI  - Correlations in survivin expression with the expression of p53 and bcl-2 in
      invasive ductal carcinoma of the breast.
AB  - This work studied the correlations between survivin, bcl-2 and p53 in
      infiltrating ductal carcinoma of the breast. A total number of 382 cases were
      collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were
      detected by immunohistochemistry on samples prepared from tissue blocks.
      Significant correlations were found between tumor histological grades and tumor
      size and lymph node involvement. Highly significant statistical correlations
      (p<0.001) were found in expression of the markers under study. It is concluded
      that such significant correlations may imply that the alterations in the
      expression take place in a concerted fashion, implying that many of these cases
      may share common abnormalities.

PMID- 18041311
TI  - Plasma D-dimer levels in patients with typhoid fever.
AB  - The plasma levels of D-dimer can be used as a marker of fibrin formation and
      degradation. Plasma D-dimer levels in the febrile phase of 6 patients with
      typhoid fever and in the afebrile convalescent phase of 4 of them were measured.
      D-dimer levels were high in the febrile phase of all 6 patients and within normal
      range in the afebrile convalescent phase of all 4 patients. Our results indicate
      that thrombus formation and fibrinolysis may occur in the febrile phase of
      patients with typhoid fever.

PMID- 18041312
TI  - Socioeconomic considerations regarding a land mine victim with maxillofacial
      injuries.
AB  - This article describes a case we experienced while doing volunteer medical work
      in Cambodia for six months in 2002. By examining treatment of a 14-year-old
      female land mine victim with maxillofacial injuries, we report on the present
      socio-medical situation in Cambodia. This case suggests the lack of
      infrastructure, facilities, human resources, and patient education make it
      extremely difficult to provide patients with proper treatment, including general
      anesthesia. A comparison of land mine victim statistics between 2002 and 2005
      reveals significant problems.

PMID- 18041313
TI  - Effects of tobacco smoking on alpha-2-macroglobulin and some biochemical
      parameters in Thai males.
AB  - This cross-sectional study was carried out among smokers and nonsmokers from
      suburban and urban residential areas in Bangkok, Thailand. One hundred eighty-six
      smokers and 102 nonsmokers, who voluntarily participated in the study, were
      investigated. The levels of alpha-2-macroglobulin (A2M), albumin, total protein,
      and other biochemical and hematological parameters as well as body mass index
      (BMI) measurements were taken. The levels of A2M, BUN and WBC counts were
      significantly higher in smokers than nonsmokers. Total protein and albumin
      concentrations were significantly lower in smokers than nonsmokers, but the
      levels of other biochemical parameters did not differ between the two groups. The
      relationship between BMI and median A2M levels in the smoker and nonsmoker groups
      showed the higher the BMI, the lower the serum A2M levels. Smokers had a higher
      percentage of hyperalpha-2-macroglobulinemia than nonsmokers. A2M concentrations
      correlated inversely with BMI, BUN, albumin, total cholesterol, triglycerides,
      and the quantity of cigarettes smoked for the total period of smoking (cigarette
      pack-years). Multiple regression analysis revealed that albumin and cigarette
      pack-years were the most closely related variables to A2M concentrations among
      smokers. These findings suggest cigarette smoking affects inflammation markers,
      increasing A2M and WBC and decreasing albumin. This effect may be the mechanism
      responsible for the development of chronic disease states associated with smoking
      since cigarette smoke contains many toxic compounds harmful to health.

PMID- 18041314
TI  - Antenatal care procedures and information reported by women in three rural areas
      of Vietnam.
AB  - The objective was to identify factors related to antenatal care (ANC) procedures
      and information reported by women in Long An, Ben Tre, and Quang Ngai Provinces.
      Cross-sectional surveys were conducted. Women who had ANC during a previous
      pregnancy were asked if they had received any of 13 procedures and information.
      The Donabedian quality of health model was used to select potential related
      factors. Data from 857 women were available for analyses. Only 24% of the women
      reported ten items or more. The mean number of items reported was seven. Factors
      related to reporting fewer items were living in Quang Ngai (OR = 0.3, 95% Cl =
      0.2-0.6), having ANC at private facilities (OR = 0.4, 95% Cl = 0.2-0.7), having
      ANC delivered by nurses or assistant doctors (OR = 0.6, 95% Cl = 0.3-0.9), and
      unplanned pregnancy (OR = 0.5, 95% Cl = 0.3-0.9). Factors related to reporting
      more items were being housewives (OR = 1.7, 95% Cl = 1.0-2.8), consumption of
      iron/folate tablets (OR = 4.2, 95% Cl = 2.2-8.2), more use of ANC services (OR =
      2.1, 95% Cl = 1.4-3.2 for sufficient utilization and OR = 3.8, 95% Cl = 2.1-7.0
      for sufficient plus), more perceived helpfulness of ANC (OR = 3.0, 95% Cl = 1.9
      4.8) and high satisfaction with ANC received (OR = 1.6, 95% Cl = 1.0-2.6). The
      most effective interventions would be to improve the quality of health facilities
      and of ANC providers, and to educate women to make sufficient number of ANC
      visits and to seek ANC from qualified ANC providers.

PMID- 18041315
TI  - Social support among elderly in Khon Kean Province, Thailand.
AB  - The purpose of this research was to assess perceived social support and its
      factors among the elderly. The study group included 734 elders who were aged 60
      years old or more, and living in eight villages in Khon Kaen Province, Thailand.
      A structured questionnaire was used to collect the information, and perceived
      social support was measured by PRQ85. This study found a high level of social
      support was perceived among the elderly. According to the PRQ85, the highest
      dimension of social support was the availability of information, emotional, and
      material support; while the lowest dimension was being an integral part of a
      group. Results from multiple regressions indicate that education level, number of
      close friend, knowing community health staff, working status, elderly club
      member, and religious activities were statistically significantly related to
      perceived social support. In conclusion, the elderly had a high level of social
      support. Close friends and community health staff are important sources of
      support among the elderly.

PMID- 18041316
TI  - The incidence of hypertension among a select population of adults in the Niger
      Delta region of Nigeria.
AB  - The incidence of hypertension was studied in two hundred male and female subjects
      engaged in low socioeconomic class occupations in a university village of the
      Niger Delta region of Nigeria. The mean age of the male subjects was 23 years and
      that of the female subjects was 25 years. The mean body mass index (BMI) for the
      male subjects was 22.7 kg/m2 and that of the females was 23.8 kg/m2. The mean
      systolic blood pressure of the male subjects was 136.8 mmHg and that of the
      females was 122 mmHg. The mean diastolic blood pressures for the male and female
      subjects were 81 and 83.4 mmHg, respectively. The incidence of hypertension among
      the male subjects was 16% and that of the female subjects was 12%.

PMID- 18041317
TI  - Safer childbirth: the big picture.

PMID- 18041318
TI  - Adverse clinical incidents: support for midwives.

PMID- 18041319
TI  - Studying: ways to survive and thrive.

PMID- 18041320
TI  - Public health: why the debate?

PMID- 18041321
TI  - Campaign for normal birth. Beware of institutional defences!

PMID- 18041322
TI  - Telephone triage in maternity care.

PMID- 18041323
TI  - Birth centres: financially viable?
AB  - The financial issues for birth centres are: Those that conduct a small number of
      births--certainly those conducting less than 100 births a year--are unlikely to
      generate income that covers their costs; In future, all community activity will
      come under PbR and it will then be much easier to identify how much antenatal and
      postnatal activity occurs from birth centres and what income should therefore be
      derived from that activity; Even if a birth centre is financially viable in its
      own terms, will it make economic sense as part of the entire maternity service?
      For a freestanding unit, it is clear that in terms of economies of scale, two
      sites will almost always be more expensive than one; For birth centres to
      survive, they must be able to demonstrate a sound business case that balances
      financial affordability with the wider policy agenda. The business case for birth
      centres has to be made in terms that make sense to the rest of the NHS.

PMID- 18041324
TI  - Can doulas provide a continuity of care that midwives are unable to?

PMID- 18041325
TI  - Putting the "shared" in informed shared decision making.

PMID- 18041326
TI  - Citation analysis of the maternal/child nursing literature.
AB  - Few bibliometric studies have been done of the nursing literature; however, much
      can be learned about nursing and specialty areas of clinical practice by
      examining the articles published in nursing journals. The purposes of this study
      were to describe the extent of research, clinical, and evidence-based practice
      articles published in maternal/child nursing journals and the information sources
      used to develop that literature. A total of 112 articles and 2571 citations from
      three randomly selected maternal/child nursing journals were analyzed. Nearly
      half (n=51, 46%) of all articles were reports of original research studies.
      Research publications were cited most frequently including research studies
      published in medical journals (n=687, 26.7% of all the cited documents), followed
      by research studies published in nursing journals (n=371, 14.4%) and journals in
      other disciplines. The maternal/child nursing journals examined in this study are
      disseminating research findings to nurses for use in clinical practice.

PMID- 18041327
TI  - Abbreviations and acronyms in healthcare: when shorter isn't sweeter.

PMID- 18041328
TI  - Adverse effects of pediatric emergency sedation after discharge.
AB  - PURPOSE: Sedation is commonly performed in children in the emergency department.
      However, little is known about adverse events that may occur after discharge.
      This study was conducted to evaluate adverse effects occurring after discharge in
      children following sedation in the emergency department. METHODS: Parents of 547
      children receiving sedation in the emergency department of a pediatric, academic
      hospital were called A approximately 24 hours af t er discharge a nd asked to
      complete a telephone questionnaire. Data were analyzed using descriptive
      statistics. RESULTS: At least one adverse effect was reported in 42% of
      participants after discharge. This included lethargy (12%), vomiting (7%),
      behavioral changes (7%), headache (6%), balance/gait disturbances (5%), nausea
      (4%), sleep disturbances (4%), nightmares (4%), hallucinations (2%), and ear pain
      (0.2%). CONCLUSIONS: Children experience minor adverse effects from sedation
      after discharge from the emergency department. Anticipatory guidance about these
      adverse effects should be given to parents and caregivers prior to discharge.

PMID- 18041329
TI  - Stress and coping responses to proficiency testing in school-age children.
AB  - Nurses encounter school-age children experiencing multiple stressors and stress
      symptoms. Performance on proficiency tests is viewed as stressor. The purpose of
      this repeated measures study was to assess 53 fourth grade children's appraisal
      of proficiency tests, concurrent stressors, stress symptoms, and coping
      strategies. During October, February, March, and April, children completed a
      ranking of their stress associated with proficiency testing and also reported
      their stressors, stress symptoms, and coping strategies. Results indicated that
      children appraised proficiency tests as most stressful at the beginning of the
      school year but less stressful at the time of the test. Stressors and stress
      symptoms increased from baseline to 1 month before testing then declined. The
      number of coping strategies used by the children decreased throughout the year.
      Nurses can work with parents and teachers to identify children with test anxiety
      and target these children for interventions to improve their coping strategies.

PMID- 18041330
TI  - Parenting children under three years of age in a south Indian setting.
AB  - A cross sectional study design to assess the knowledge, attitude, and practice of
      mothers regarding parenting of children less than 3 years of age was conducted
      with 120 mothers from both rural and urban areas of South India. Mothers were
      interviewed in their homes using a structured questionnaire. The nutritional
      status of their children was assessed by Anthropometry IAP (Indian Academy of
      Paediatrics) classification and Waterloo's classification were used to assess
      their children's nutritional status, and the Thiruvananthapuram Development
      Screening Chart [TDSC] was used to assess the children's development. The
      majority of mothers had moderately adequate knowledge regarding parenting. The
      mother's level of education had a significant association (p < 0.05) with their
      practice and attitude. The study brought out the association between
      sociodemographic variables and knowledge, attitude, and practice of mothers and
      its impact on growth and development of their children. Results provide direction
      for nurses in developing better life style education and parenting training
      programs.

PMID- 18041331
TI  - The many roles of families in family-centered care--part VI.
AB  - The mother of a child with cystic fibrosis describes her journey from sorrow and
      fear to hope. Her journey to hope began as partnership with a knowledgeable
      pediatrician and cystic fibrosis team. The journey wound through demanding care
      requirements, anguishing questions, and new realizations. The support of friends,
      and immersion in information about the disease, were also empowering. An
      introduction to the Cystic Fibrosis Foundation led this mother to volunteering,
      then to serving on a chapter Board of Directors, and finally to employment by the
      Foundation as a fundraiser. Both parents and health care organizations benefit
      from such arrangements. As this author states: "Working with the Cystic Fibrosis
      Foundation gives me a 'big picture' view of the state of my daughter's disease,
      and a sense of contributing a small part to the product of its big mission to
      cure and control CF, and [gives me] hope."

PMID- 18041332
TI  - She passed out again. Astrocytomas.

PMID- 18041333
TI  - How low can you go? Diastolic hypotension.

PMID- 18041334
TI  - The role of pediatric primary care providers in parental smoking cessation:
      assessing and motivating parents to quit.
AB  - Children and adolescents who are exposed to smokers in their household are 3
      times more likely to initiate smoking themselves (Winickoff, Berkowitz, et al.,
      2005). If successful in getting parents to quit smoking, pediatric providers will
      have helped parents and their families improve quality of life standards in a
      variety of ways, including adding 7 years to the parent's life and eliminating
      the majority of second-hand smoke exposure in children. The purpose of this
      clinical article is three-fold; (1) to discuss the role of pediatric primary care
      providers in parental smoking cessation, (2) to discuss the obstacles faced by
      parents in smoking cessation and how the primary care provider can help them to
      surmount them, and (3) to discuss the obstacles faced by pediatric primary care
      providers in assisting parent smoking cessation and options to surmount them.

PMID- 18041335
TI  - Financial analysis of acetaminophen suicide in a teen girl.
AB  - There is no doubt that prevention and primary care treatment is less costly than
      emergency room efforts and tertiary care to save someone's life. Preventive
      health care is the cornerstone of any health care system designed to reduce costs
      and human suffering (American Nurses Association, 1997). Unfortunately, emergency
      room and intensive care nurses frequently care for critically ill children and
      adults who suffer from conditions that might have been prevented. This case study
      presents the financial breakdown of the costs at each level of care for an 18
      year-old college student who suffers terrible consequences of an acetaminophen
      overdose.

PMID- 18041336
TI  - Foot soldiers against infectious diseases: nurses, families, and immunization in
      the twentieth century.

PMID- 18041337
TI  - Homosexuality in children and/or their parents.

PMID- 18041338
TI  - The gift of life: a nursing grand rounds presentation on organ and tissue
      donations.

PMID- 18041339
TI  - School guidelines for managing students with food allergies.

PMID- 18041340
TI  - Braces: treatments to ensure a healthy smile.

PMID- 18041341
TI  - Childhood vision. What the research tells us.

PMID- 18041342
TI  - When your child is diagnosed with diabetes: parents' questions for the healthcare
      team.

PMID- 18041343
TI  - On being a school nurse: the value of reflection and humor.

PMID- 18041344
TI  - Weighing in on disordered eating.

PMID- 18041346
TI  - The medication-adherence dilemma.

PMID- 18041345
TI  - Identifying and treating anaphylaxis in the school setting.

PMID- 18041347
TI  - The heart of the matter: the relationship between communities, cardiovascular
      services, and racial and ethnic gaps in care.
AB  - Racial and ethnic disparities in cardiovascular care are greatly influenced by
      market factors and how the health care system is organized. This study examines
      key health system factors that contribute to disparities in cardiac care among
      racial and ethnic minorities in the United States. A market assessment,
      consisting of site visits, interviews, and data collection from key health care
      providers in 10 communities, was undertaken to identify common characteristics in
      the health care markets and to explore how these factors may drive disparities in
      cardiac care.

PMID- 18041348
TI  - Thiazolidinediones and slowing the progression of diabetes.
AB  - A continuing goal of treatment of diabetes is to slow the progression of the
      disease through the preservation of beta-cell function. To assess efficacious and
      cost-effective methods of doing this, The Pharmacy & Therapeutics Society
      (Glastonbury, CT) assembled a study group of health plan medical directors. Based
      on a review of the data, the group studied the value of earlier diagnosis and the
      administration of thiazolidinediones. The potential role for health plans to
      support this approach to diabetes care is outlined below.

PMID- 18041349
TI  - Measurement of physician quality in manage care.

PMID- 18041350
TI  - Certification program offers new competencies for chronic-care improvement.

PMID- 18041351
TI  - From silos to synergy.
AB  - Texas Children's Health Plan (TCHP) redesigned its approach to care management in
      an effort to provide support for member-centric care and the medical home. The
      changes in process and structure focused on connecting information and programs
      to promote care for members in a collaborative manner and taking advantage of the
      synergy between staff, programming, and the physician practices serving health
      plan membership. The results brought about an improvement in job satisfaction,
      positive change in the medical-loss ratio, and new innovations to support
      preventive and chronic care service delivery needs of the TCHP membership.

PMID- 18041352
TI  - Who should determine the psychiatric BSN curriculum?

PMID- 18041353
TI  - Limitations of evidence in the practice of evidence-based medicine.
AB  - The goal of evidence-based medicine (EBM) is to support population-based policies
      and individual medical decisions that serve to improve health outcomes through
      the use of the most proven effective treatments. The essence of EBM is to use
      evidence (typically research data) related to the effectiveness of medical
      interventions to guide decisions about whether to use those interventions in
      clinical practice. The quality of evidence is the critical component in
      understanding and using EBM. This article discusses the kinds and limitations of
      the evidence used in the practice of EBM.

PMID- 18041354
TI  - Caring for the caregivers.
AB  - National Family Caregivers month is a reminder of the invaluable contributions of
      family caregivers--contributions that are too often unrecognized when addressing
      the costs of health care. Unpaid caregivers spend a substantial percentage of
      each week "helping out," often with older relatives, which requires major changes
      in their work patterns. It is clear that these caregivers may need help balancing
      their work and caregiving responsibilities, and it is tempting to want to help
      them by "taking over" some of the seemingly overwhelming tasks they face daily.
      Yet, it is also important to recognize the ways in which these tasks may enrich
      caregivers' own quality of life. Through listening to caregivers, nurses and
      other health care professionals can better understand the embedded values, goals,
      joys, and disappointments that connect their lives with those for whom they care.

PMID- 18041355
TI  - Mindfulness: an intervention for anxiety in schizophrenia.
AB  - Despite evidence that individuals with schizophrenia spectrum disorders
      experience significant and persistent symptoms of anxiety, there are few reports
      of the use of empirically supported treatments for anxiety in this population.
      This article describes how we have tried to adapt mindfulness interventions to
      help individuals with schizophrenia who experience significant anxiety symptoms.
      Although mindfulness has been widely used to help individuals without psychosis,
      to our knowledge, this is the first study adapting it to help those with
      schizophrenia manage worry and stress. We provide an overview of the intervention
      and use an individual example to describe how our treatment development group
      responded. We also explore directions for future research of mindfulness
      interventions for schizophrenia.

PMID- 18041356
TI  - The Transitional Discharge Model: comparing implementation in Canada and
      Scotland.
AB  - Effective discharge planning is needed to facilitate clients' transition from
      psychiatric hospital wards to community care. Previous studies have shown that
      client outcomes can be improved by using a Transitional Discharge Model (TDM)
      that includes peer support and an extension of inpatient-practitioner
      relationships that are introduced prior to discharge. However, countries vary in
      many ways that may affect implementation of the model. This article describes
      some of the similarities and differences related to introducing transitional
      discharge in two countries: Canada and Scotland. It is important to elucidate
      facilitators and challenges in implementing the TDM to identify and disseminate
      strategies to aid implementation. Implications for future implementation of the
      model are also discussed.

PMID- 18041357
TI  - Well balanced: 8 steps to wellness for adults with mental illness and diabetes.
AB  - Serious mental illness places a tremendous burden on clients, their families, and
      behavioral and medical health care providers. The co-occurrence of diabetes with
      mental illness may further compromise daily functioning. Psychiatric nurses can
      make a significant difference in improving the health and medical outcomes of
      this client population. A partnership was developed between the University of
      Rochester School of Nursing and the Western New York Care Coordination Program to
      evaluate a novel nursing model for adults with both serious mental illness and
      diabetes mellitus. The Well Balanced program incorporated health promotion,
      disease management, nursing care management, and evidence-based practice
      guidelines into 8 Steps to Wellness for a community-based mental health
      population. During a 16-visit intervention period, psychiatric nurses interacted
      with 74 clients. As a result of the program, clients experienced improvements in
      health risk status and in their hemoglobin A1C and reported high satisfaction
      with the Well Balanced program.

PMID- 18041358
TI  - Quality of life evaluation by the EORTC QLQ-C30 questionnaire in patients treated
      with hormonal treatment in Italy. A QuABIOS group study.
AB  - OBJECTIVES: An observational study was planned by the QuABIOS group, to survey
      the hormonal treatment administered to prostate cancer patients in Italy within a
      time window of 12 months. We report here a prospective quality of life (QOL)
      evaluation over time and by hormonal treatment modalities. METHODS: Patients with
      diagnosis of prostate cancer and treated with hormonal therapy were eligible for
      this study. The EORTC QLQ-C30 v.3 questionnaire was administered at enrolment,
      after 6 months and after 12 months from enrolment. RESULTS: 587 patients were
      enrolled by 33 urological centers. When 1518 visits were considered together
      independently of time, antiandrogen monotherapy was associated with a
      significantly better QOL than LHRH-analogue containing treatment modalities in
      almost all functional scales; cyproterone acetate demonstrated a better physical
      function and general health status than bicalutamide. When QOL was analyzed in a
      prospective 12-month window, a worsening of physical function and general health
      status was observed, notwithstanding, antiandrogens remained significantly
      associated to a better QOL than LHRH-analogue therapies also over time: a
      favourable physical function and general health status appeared again to be
      related to cyproterone acetate than bicalutamide. CONCLUSIONS: Androgen
      deprivation therapy is associated with decline in QOL, particularly in the
      domains of physical function, energy, and general health status. This survey
      demonstrated that antiandrogens had a better QOL profile than LHRH-analogue
      containing therapies;furthermore, a more favourable tolerability for cyproterone
      acetate as compared to bicalutamide is suggested.

PMID- 18041359
TI  - Economic evaluation of different hormonal therapies for prostate cancer. Final
      results from the Quality of Life Antiandrogen Blockade Italian Observational
      Study (QuABIOS).
AB  - OBJECTIVE: The paper compares costs and Quality-Adjusted Life Years (QALYs) of
      different hormonal therapies (HTs) administered to 275 out of 471 patients with
      prostate cancer (PC) enrolled in the Quality of Life Antiandrogen Blockade
      Italian Observational Study (QuABIOS), who did not change HT during the study
      period. METHODS: QALYs and costs related to monoHT witk cyproterone acetate (CYP)
      (42 patients); bicalutamide (BIC) (41 patients); LHRH-a (96 patients) and
      complete androgenic blockade (CAB) with: CYP (CYP CAB) (50 patients); BIC (BIC
      CAB) (46 patients) were compared via a cost-utility analysis (CUA) adopting the
      Italian National Healthcare Service (INHS) viewpoint. RESULTS: As no statistical
      significant difference among the mean QALYs gained with the different HTs was
      detected (p = 0.116), CUA was replaced by a cost minimization analysis (CMA).
      However, the lowest and the highest mean QALYs gained per patient were registered
      for BIC CAB (0.59; 95% CI: 0.50; 0.68) and for for CYP (0.75; 95% CI: 0.68;
      0.82), respectively. CYP was the least costly HT, reaching the lowest and the
      highest savings when compared to LHRH-a (-Euros 974.99; 95% CI: -Euros 1066.86; 
      Euros 883.12; p<0.0001) and to monoHT with BIC (-Euros 5887.81; 95% CI: -Euros
      6143.99; -Euros 5631.64; p<0.0001). A nonparametric bootstrap sensitivity
      analysis confirmed the robustness of the base case CMA. CONCLUSION: CYP is an
      interesting option for curbing the INHS drug expenditure for PC patients, with a
      trend towards increasing the mean number of QALYs gained.

PMID- 18041360
TI  - A novel spectral ultrasonic differentiation method for marking regions of
      interest in biological tissues. In vivo preliminary results.
AB  - BACKGROUND: "in vivo" application of a new echographic method able to better
      identify neoplastic tissue. The aim of this study was to evaluate its accuracy in
      the diagnosis of prostate cancer. MATERIALS AND METHODS: Double-blind prospective
      study on 60 patients (pts) submitted to both transrectal ultrasound (TRUS) of
      prostate with a traditional echograph connected to a new hardware/software
      platform named FEMMINA (Fast Echographic Multiparameter Multi Image Novel
      Apparatus) that processes the echo signal by RULES (Radiofrequency Ultrasonic
      Local EStimators) algorithm and to a prostatic biopsy (8 to 12 cores).
      Histological findings of biopsies were compared to B-mode and the new ultrasound
      method. RESULTS: Cancer was detected in 18/60 pts. 14 patients had positive
      images with RULES, 11 with B-mode modality. The positive predictive value (PPV)
      and negative predictive value (NPV) of B-mode were 42% and 79% while 77% and 90%
      of RULES. Sensitivity and specificity of B-mode were 61% and 79% while those of
      RULES were 77% and 90%. B-mode diagnostic accuracy was 63% and RULES accuracy was
      86%. CONCLUSIONS: Results obtained with RULES are encouraging but they need
      further studies for its application in clinical practice.

PMID- 18041361
TI  - The cost of treatment and follow-up of bladder cancer in Italy.
AB  - OBJECTIVES: To evaluate the costs of bladder bladder cancer treatment and follow
      up. MATERIALS AND METHODS: A purely economic analysis was carried out evaluating
      in our Institution a) the cost of an hospital stay of patients submitted to
      transurethral resection of superficial bladder cancer and to radical cystectomy
      for invasive bladder cancer, b) the cost of endovesical immuno-chemotherapy
      performed as day hospital regimen, c) the cost of the first year of follow-up
      according to European Association of Urology's Guidelines as outpatient regimen.
      RESULTS: The total cost related to a superficial tumour of the bladder treated
      with an endoscopic resection amounts to Euro 2,242.20, while in case of invasive
      bladder cancer treated with a radical cystectomy it comes to Euro 6,860. For
      chemo-immunotherapy the costs in a day hospital regimen related to a 8-weekly
      session of mitomicin, 6-weekly session of epirubicin and BCG are Euro 1,420, Euro
      1,037 and Euro 975, respectively. The first year of follow-up for a patient with
      low risk of superficial bladder cancer without recurrence costs Euro 265.15. In
      case of high risk superficial bladder cancer the cost reaches Euro 321.75. In
      case of a patient with invasive bladder cancer in the first year, when follow-up
      is more strict, expenses amount to Euro 548.90. CONCLUSIONS: Cancer bladder is a
      high-cost illness due, in particular, to its heterogeneity in presentation and
      high rate of recurrences which makes any evaluation underestimated. The
      possibility of containing costs is essentially related to optimization of the
      follow-up and to the development of optimal therapeutic procedures which could
      lead to a reduction in the number of recurrences.

PMID- 18041362
TI  - Sexual education and temporary total androgen blockade in the fight against
      heroin addiction: a new hypothesis.
AB  - Various theories have been advanced to account for heroin addiction. One of the
      causes, upon which little attention has, so far, been focused, concerns the
      relationship with testosterone and with sexual distress. In the present report, a
      new strategy in the fight against heroin use is proposed which is based upon the
      assumption that testosterone, or its metabolites, would exert on drug seeking
      behaviours and drug taking behaviours through a direct effect upon the rewarding
      circuit or indirectly eliciting the drug craving and by leading some youths with
      sexual distress to seek improvement in their sexual performance with the use of
      drugs. The new strategy proposed here is based upon sexual and affectivity
      education in adolescents to prevent First Drug Use and for those already
      addicted, upon sexual and affectivity education and temporary total androgen
      blockade with pharmaceutical agents that, in a reversible fashion, block both the
      production and the effect of testosterone and their metabolites until complete
      disintoxication of drug use is reached.

PMID- 18041363
TI  - Fistulas between lower urinary tract and bowel: our experience in 15 years.
AB  - OBJECT: Fistulas between bowel and low urinary tract are not frequent and could
      be due to different causes. Diagnosis and treatment need a particular care to
      assure to patient a good result. Authors report their last 15-years experience.
      MATERIALS AND METHODS: From 1990 and 2005 22 patients have been quite carefully
      investigated and surgically treated; 17 men and 5 women of age between 39 and 81
      years old. In particular 2 vesico-ileal fistulas, 12 colo-vesical have been
      treated: in all these situations we proceed by intestinal resection and fistulas
      repairing at the same time. Three rectovesical and 3 recto-urethral fistulas have
      been treated by fistula's way removal (with different approaches) and in a case
      by preparing a definitive urinary derivation. Finally, 2 complex fistulas have
      been treated by preparing a definitive urinary derivation. RESULTS: The typical
      symptoms presence must be carefully researched because it could be useful in
      diagnosis; radiological and endoscopic procedures could be useful for treatment
      planning, also if they have a quite low sensibility. In 20 cases, the treatment
      has achieved a good and lasting result. In 1 case we had a relapse, in another
      one patient died for sepsis. CONCLUSION: Diagnosis of fistulas has to be quite
      careful and it is necessary to plan the treatment, that is always surgical, also
      considering that sometimes it's leading to serious complications.

PMID- 18041364
TI  - A cost comparison of laparoscopic versus open radical cystoprostatectomy and
      orthotopic ileal neobladder at a single institution.
AB  - AIM OF THE STUDY: To evaluate the specific cost components in two similar groups
      of patients who underwent laparoscopic or open radical cystoprostatectomy with
      orthotopic ileal neobladder at our Institution. METHODS: Between November 2000
      and July 2004, 20 men with transitional cell carcinoma of the bladder underwent
      laparoscopic (group 1) or open (group 2) radical cystoprostatectomy with
      orthotopic ileal neobladder. We evaluated the costs of hospital stay, surgical
      consumables and operating room occupation. At our Institution one day of hospital
      stay costs Euro 625 while one hour of operating room costs Euro 520 (professional
      fees included). RESULTS: Hospital stay and operating room occupation in group 1
      and 2 were statistically different (respectively 395.5 versus 275 min and 10.5
      versus 18.9 days). Surgical consumables cost Euro 637 for patients in group 1
      versus Euro 270 for patients in group 2. With the considered issues, at our
      Institution laparoscopic radical cystoprostatectomy costs Euro 10,626 whereas
      open radical cystoprostatectomy costs Euro 14,465. CONCLUSIONS: Laparoscopic
      radical cystoprostatectomy seems associated with a shorter hospital stay and with
      a reduction of costs if compared to the open approach.

PMID- 18041365
TI  - Multifocal and bilateral renal oncocytoma: a case report and review of the
      literature.
AB  - A 78-year-old man presenting with synchronous, multifocal and bilateral renal
      oncocytomas underwent a staged nephron-sparing surgery with removal of six
      lesions. At 14-month follow-up the renal function was preserved and no recurrent
      disease was evident. A literature review demonstrated 17 similar cases, treated
      either with watchful waiting or with complete surgical removal. Reasons to prefer
      the surgical option are herein substantiated.

PMID- 18041366
TI  - First case of bilateral intratubular germ cell tumor in androgen insensivity
      syndrome.
AB  - INTRODUCTION AND OBJECTIVE: Androgen insensivity syndrome is an X-linked
      recessive disorder caused by a mutation of the androgen receptor gene localized
      in Xq 11-q12-b. Affected males have a female phenotype with undescended testis.
      Aim of the study is the description of the first case of bilateral intratubular
      germ cell tumor in androgen insensivity syndrome. METHODS: In September 2002, a
      24-year-old woman with XY karyotype and childhood diagnosis of complete
      testicular feminization first came under our observation. An abdominal ultrasound
      showed, in correspondence with the inguinal canal, bilaterally, two oval
      formations with a diameter of about 45 x 20 mm, referable to gonads. Only for the
      right gonad, furthermore, the presence of a round anechoic image could be seen,
      of about 1.5 cm and small multiple microcalcifications (6). Explorative
      laparoscopy and bilateral orchiectomy were carried out. RESULTS: Histological
      examination revealed the presence of a bilateral intratubular germ cell tumor. A
      review of the literature on this subject did not yield any adjuvant therapy or
      standardized follow-up for these patients. We thought it advisable not to carry
      out any adjuvant therapy, and to follow the patient with abdomen/pelvic CT scans.
      The current follow-up after four years is negative for relapses. CONCLUSIONS:
      Post-pubertal bilateral orchiectomy, considering the relevant chances of
      neoplastic progression of the undescended testis, is the therapy chosen for
      patients with androgen insensivity syndrome. In patients with TIN, orchiectomy is
      a valid therapeutic option, followed by a strict follow-up abdomen/pelvic CT
      scan, chest XR, tumor markers every three months for the first two years.

PMID- 18041367
TI  - Low velocity gunshot wound to the penis.
AB  - A ricocheting 30-06 calibre bullet caused a low velocity penile injury in a 54
      year-old man, shearing the right corpus cavernosum and crossing the ipsilateral
      thigh and gluteal muscles. Prompt surgical exploration with meticulous
      debridement and corporeal reconstruction through a degloving incision led to
      excellent cosmetic and functional results.

PMID- 18041368
TI  - Estradiol plasma levels elevation during follow-up for testicular Leydig-cell
      tumor is not an unfailing sign of recurrence.
AB  - We report a case of a benign testicular Leydig-Cell Tumor (LCT) that deceived us
      because of an estradiol (E2) plasma levels elevation 27 months after radical
      orchiectomy in a body builder patient with habits of red meat abuse and no
      steroid assumption, without any sign of tumor recurrence. The patient was
      therefore asked to stop red meat assumption and E2 plasma levels returned normal.
      The restoration of red meat assumption showed a trend of increasing E2 plasma
      levels above normal range. Despite the documented usefulness of E2 plasma levels
      evaluation during the follow-up of LCT, elevation of this hormone could be
      related to other causes and presence of the so-called evironmental xenoestrogens
      may be one of these.

PMID- 18041369
TI  - The view from down under: a test of the multiregional hypothesis of modern human
      origins using the basicranial evidence from Australasia.
AB  - Proponents of the Multiregional Hypothesis of modern human origins have
      consistently stated that Australasia provides one of the most compelling examples
      of regional continuity in the human fossil record. According to these workers,
      features found in the earliest Homo erectus fossils from Sangiran, Central Java,
      can be traced through more advanced hominids from Ngandong and are found in
      fossil and recent Australian Aborigines. In order to test the hypothesis that a
      close evolutionary relationship exists amongst the fossils from Australasia, this
      study will examine the cranial base. This region of the skull is considered to be
      evolutionarily conservative and has relatively good representation and
      preservation throughout much of the Australasian record. The results of this
      project highlight a number of features on the cranial base in the Ngandong sample
      that appear to be unique not only within the region, but in the human fossil
      sample as a whole. Several of these features, such as the morphology of the
      foramen ovale, the location of the squamotympanic fissure in the roof of the
      temporomandibular fossa, and the extreme expression of the postcondyloid
      tuberosities have been pointed out by workers such as Weidenreich and Jacob in
      their surveys of this material. The presence of these characters in the Ngandong
      population, and their apparent lack of expression outside of this group, provides
      strong evidence of discontinuity in the Australasian fossil record.

PMID- 18041370
TI  - Variation of pelvic diameters due to different scanning positions--the
      experimental study.
AB  - The distortion of human pelvis X ray scans, due to different scanning positions,
      can cause huge mistakes in estimation of pelvic diameters. The aim of the study
      was to quantify distortion of pelvic diameters in relation to scanning
      inclination angles. Twenty anatomically defined spots on the pelvis of a young
      male cadaver, freed of soft tissues, were marked with 3 mm metal balls. The
      digitalized X-ray scans were made with seven different but similar inclination
      angles, and marked spots were recognized by computer software. Obstetrical
      gynecological (Ob-Gyn), horizontal and vertical diameters were measured between
      marked spots, and percentages of distortion were calculated for each new scanning
      position. Twenty seven distances on human pelvis from seven X-ray scans varied
      from -35.9% to 28.3%, on average 0.47%. This study has pointed to a high
      variation of vertical pelvic dimensions (4.94 +/- 5.73%), consequently making
      them unreliable in the estimation of general pelvic shape, and low variation of
      horizontal dimensions (0.92 +/- 0.61%). Generally, the percentage of variation of
      pelvic dimensions highly increases with inclination angle, in frontal and
      sagittal plane. Alteration of scanning distance by 4 cm has a weak influence on
      pelvic diameters. The most reliable Ob-Gyn pelvic diameter was conjugata
      diagonalis, then diameters obliqua prima and secunda, with an average length
      deviations of 3.4, 4.0, and 6.0% respectively. The conjugata anatomica was the
      most unreliable with an average variation of 11.5%.

PMID- 18041371
TI  - Science attitudes and knowledge among preclinical medical students in Pokhara,
      Nepal.
AB  - Knowledge of science and the scientific method are important in learning about
      and using evidence-based medicine in practice. Courses in research methodology
      have been introduced for both medical students and practicing doctors. In
      Pokhara, the basic science subjects are taught in an integrated manner during the
      first four semesters of the undergraduate medical course. Studies on students'
      attitudes towards and knowledge of science are lacking in medical colleges in
      Nepal. Hence the study was carried out to obtain information on students'
      attitude towards and knowledge of science and scientific methodology among
      preclinical medical students and note the association, if any, of students'
      attitudes and their demographic characteristics. The study was carried out in
      March 2005 among the students of the first four semesters at the Manipal College
      of Medical Sciences, Pokhara, Nepal using a questionnaire developed by Hren and
      coworkers. Two hundred and twenty students (overall response rate 73.3%)
      successfully completed the questionnaire. Seventy-five respondents were Nepalese,
      115 were Indians, 27 were Sri Lankans and 3 belonged to other nationalities. The
      X +/- SD total attitude score was 147.4 +/- 10.8 (neutral score 135). The X +/-
      SD scores on the subscales, value of science to humanity, value of scientific
      methodology and value of science to medicine were 51.3 +/- 5.4, 39.6 +/- 3.7 and
      58.5 +/- 5.9 (neutral scores were 36, 51 and 48 respectively). The knowledge
      score measured using a set of 8 multiple choice questions was 3.3 +/- 1.4. The
      attitude scores were lower and the knowledge score was comparable to that
      reported previously in a study in Croatia but higher than that reported from
      Southeast Europe.

PMID- 18041372
TI  - Structural analysis of dental fear in children with and without dental trauma
      experience.
AB  - The aim of the study was to evaluate dental fear in children with and without
      dental injuries in a randomly selected children in Croatia (59 girls and 88
      boys). Children were divided into three groups depending on dental trauma
      experience. They were also divided into two age groups: 5-8 and 9-12 years. Only
      dental trauma to the permanent teeth was included in the study. The CFSS-DS, CDAS
      and CMFQ were used for evaluation of dental anxiety and the ISP Hollingshead
      Index of Social Position was calculated for evaluation of social status. The mean
      values of CDAS, CFSS-DS and CMFQ tests revealed that the anxiety level decreases
      with increasing experience of dental injury. The analysis of variance performed
      for CDAS showed a significant difference between children with and without dental
      trauma (p = 0,010). Regarding the groups, the analysis of variance for CMFQ (p =
      0,021) and CFSS-DS (p = 0,001) showed a significant difference, as well as
      regarding age (CMFQ; p = 0,001 and CFSS-DS; p = 0,016). Cronbach's alpha
      coefficients revealed the highest reliability for CFSS-DS (alpha = 0,910).
      Pearson's correlation coefficients revealed significant correlations between the
      anxiety scores, age and ISP values for children without dental trauma, and
      between the anxiety scores and age for children with repeated dental trauma. The
      results of the ISP Hollingshead Index exhibited the highest frequency in children
      with dental injuries who belonged to the families with poor social background
      (ISP = 44-60). No significant difference was obtained between children with and
      without dental injuries depending on either gender or the ISP value.

PMID- 18041373
TI  - Self-reported confidence, attitudes and skills in practical procedures among
      medical students: questionnaire study.
AB  - The aim of our study was to investigate the influence of gender, loss of academic
      year(s), confidence and attitudes of students on the clinical experience gained
      by undergraduate education. The survey was conducted during 2004 and 2005 in a
      sample of 182 students of the 5th and the 6th year at J.J. Strossmayer University
      School of Medicine in Osijek. The participants were grouped and matched according
      to their gender, regular studying, the number of time(s) student has performed
      certain practical medical procedure and the self-confidence arisen by performing
      one. Furthermore, participants were grouped and compared due to their own
      assessment of their own practical and theoretical medical knowledge, courses
      which provide them the least and oppositely--the most practical medical knowledge
      and their attitude toward current medical faculty curriculum on clinical courses
      as well as the possibilities of improving them. Fisher's exact test and chi2-test
      were used to estimate statistical differences between the groups and the
      parameters in research, while coefficient of contingency was introduced with the
      aim of defining their correlation. The results showed statistically significant
      differences between male students who performed more practical medical procedures
      than female (p < 0.001), non-repeaters performed medical procedures more often
      than repeaters (p < 0.001, C = 0.658) while repeaters thought higher of their
      theoretical knowledge than non-repeaters (p < 0.005). Data analysis showed
      statistically significant correlation between clinical experience and the level
      of confidence (C = 0.944). This study confirmed influence of male gender, regular
      studying, better opinion about one's own practical skills and higher confidence
      in one's own work on greater number of clinical skills performed during
      undergraduate education.

PMID- 18041374
TI  - Is laparoscopic nephropexy improving the quality of life.
AB  - Short- and long-term effectiveness of laparoscopic nephropexy was evaluated in
      patients with symptomatic nephroptosis especially quality of life of the patients
      and repositioning of the ptotic kidney. In 87 patients with symptomatic
      nephroptosis laparoscopic nephropexy was performed from 1994 to 2003. In 86
      patients trans-abdominal approach was used and retroperitoneal in one patient.
      Visual pain scale was used for pain evaluation before surgery and six month after
      surgery. At the same period creatinine serum concentration, urine examination,
      i.v. urography and ultrasound in supine and erect position was made. There was
      statistical significant decrease of pain from 6.5 +/- 1.055 (SD) to 2.4 +/- 1.577
      (SD) (p = 0.000), according to visual scale, and decrease of urinary tract
      infections (p = 0.000) in patients after laparoscopic nephropexy. Average
      operative time was 45.9 +/- 8 (SD) min., and hospital stay 3.4 +/- 0.7 (SD) days.
      Reposition of the kidney was successful in 70 of 80 patients. Laparoscopic
      nephropexy importantly improved the quality of life in patients with symptomatic
      nephroptosis. Surgical procedure was safe and successful in most of the patients.

PMID- 18041375
TI  - Biomechanical pressures and upper extremity asymmetry: a study on young laborers.
AB  - The purpose of this study is to reveal the impacts of biomechanical pressures of
      heavy working conditions on the upper extremities of young laborers. The study
      covers the examination of the upper extremities of 104 young laborers in the
      industrial workshops of Ankara, Turkey regarding bilateral asymmetry. The average
      age of the laborers was 18.48 +/- 0.61 years. The control group consisted of 102
      non-laborers with an average age of 18.39 +/- 0.58 years. The laborers were
      measured with regard to width of elbows, wrists, and hands, and the length of
      hands. No significant difference between the groups was observed with the
      exception of average wrist width. However, while the labor group showed
      directional asymmetry in all measurements, the non-laborers exhibited directional
      asymmetry only in hand width and length. Consequently, the study revealed that
      biomechanical pressures tend to increase directional asymmetry in the upper
      extremities.

PMID- 18041376
TI  - The effects of the level of physical activity on calcaneal ultrasound
      measurements: bone properties of medical and physical education students.
AB  - The aim of the study was to compare bone properties of two groups of students
      which strongly differ in the level of their everyday physical activity; the
      School of Medicine (SM) students and the Faculty of Physical Education (FPE)
      students, University of Zagreb. Quantitative ultrasound parameters--broadband
      ultrasound attenuation (BUA) and speed of sound (SOS) were measured. Quantitative
      ultrasound index (QUI) and estimated bone mineral density (BMD) were calculated
      by the device software. The final study sample consisted of 165 students from SM
      (94 males and 71 females) and 215 students from the FPE (164 males, 51 females).
      Sixty eight percent of FPE students and 21% of SM students reported a high level
      of everyday physical activity (P < 0.001). All ultrasound parameters were
      significantly higher in FPE students than in SM students (at the P < 0.001
      level). The multiple regression model of the QUI confirmed that the school
      students attended was the single significant predictor variable for both genders.
      Our data indirectly showed the beneficial role of physical activity on bone
      properties.

PMID- 18041377
TI  - Receiver operating characteristic curve analysis of BMI in assessing obesity
      among adult Bengalee males in India.
AB  - The present study attempted to understand the appropriateness of different body
      mass index (BMI) cut-off points in assessing obesity. Four hundred thirty adult
      Bengalee males with mean age 36.48 +/- 12.23 years (mean +/- SD) from West
      Bengal, India were studied. Height, weight and percent body fat were measured and
      BMI was derived following standard equation. Receiver operating characteristic
      (ROC) curve analysis demonstrated low sensitivity and high specificity of
      international (> or = 30 kg/m2) and proposed (> or = 25 kg/m2) BMI cut-off points
      in identifying individuals with obesity. Furthermore, these international and
      proposed BMI cut-off points also found to be in substantial misclassification to
      assess obesity as much as 32.09% and 17.44% respectively. However, based on ROC
      curve analysis, a BMI cut-off point of > or = 24 kg/m2 revealed optimal
      sensitivity (83.66%) and specificity (90.61%) and as well as less
      misclassification (11.86%) in assessing obesity among the adult Bengalee males.
      The present study accentuated that the international and proposed BMI cut-off
      points so far might not be appropriate in assessing obesity and on the other
      hand, lower BMI cut-off point (> or = 24 kg/m2) has relatively high sensitivity
      and specificity in assessing obesity as well. Therefore, the present study
      envisages the requirement of further lowering down of BMI cut-off point in
      assessing excess body fat in adult Bengalee males.

PMID- 18041379
TI  - Age-sex and diurnal variation of blood pressure in different nutritional states
      among the adult Telegas of Kharagpur in West Bengal, India.
AB  - An anthropological investigation among the endogamous Telega population (106
      adult individuals including 51 males and 55 females) in the district of Paschim
      Medinipur of West Bengal, India shows wide range of age-sex as well as diurnal
      variation of mean blood pressure (MBP) with reference to different nutritional
      status. Distribution of MBP shows distinct bias for sexes separately on different
      occasions and in association with age and other physiological conditions like
      menopause in females. Records of increase of blood pressure from morning to
      evening also indicate clear diurnal change in both male as well as in the female
      samples with some variations when compared between the two sexes. Results also
      help us to understand and to record the variation of blood pressure as a
      physiometric trait in the population under study. Data indicate that nearly 30%
      of males and more than 30% of females are living at the level of undernutrition.
      Nutritional status is measured by anthropometric measurements, e.g. height,
      weight, mid arm circumference (MUAC) and further calculation of body mass index
      (BMI). Distribution of MBP at different BMI and MUAC levels and Pearson
      correlation and regression analysis--all suggest that age, BMI and MUAC have
      significant impacts on BMI with some sex-related variations.

PMID- 18041378
TI  - The prevalence of cardiovascular disease risk factors in patients from Croatian
      Zagorje County treated at Department of Medicine, Zabok General Hospital from
      2000 to 2006.
AB  - The aim of the study was to assess the prevalence of risk factors for
      cardiovascular disease in patients treated for coronary heart disease (CHD) at
      Department of Medicine, Zabok General Hospital during the 2000-2006 period.
      Cardiovascular diseases are a group of diseases that occur due to arterial. The
      risk factors that lead to the development and occurrence of cardiovascular
      disease are hypertension, cigarette smoking, hyperholesterolemia,
      hypertriglyceridemia, diabetes mellitus and positive family history. Additional
      factors favoring the occurrence of cardiovascular disease include overweight,
      inadequate physical activity, and emotional stress. Data on all patients
      hospitalized and diagnosed with CHD at Department of Medicine, Zabok General
      Hospital during the 2000-2006 period were analyzed for the prevalence of risk
      factors for CHD, i.e. hypertension, cigarette smoking, hypercholesterolemia,
      hypertriglyceridemia, diabetes mellitus and positive family history of
      cardiovascular disease. Hypercholesterolemia was defined by a cholesterol level
      higher than 5.1 mmol/L, hypertension from history data and blood pressure
      measurement on admission greater than 140/90 mmHg, diabetes mellitus from history
      data, and hypertriglyceridemia by a triglyceride level greater than 1.7 mmol/L.
      Information on heredity and cigarette smoking was collected from history and a
      questionnaire filled out on admission. All laboratory values were determined on
      patient admission to the hospital. Analysis of the risk factors for CHD recorded
      in patients from Zagorje County during the 2000-2006 period revealed hypertension
      to be the most common risk factor in our patients. According to sex, CHD was
      found to show a male preponderance. According to age at admission, CHD
      predominated in the > 70 age group, which accounted for one third of all
      patients, followed by a comparable proportion of the 50-60 and 60-70 age groups,
      i.e. still active population groups. As CHD is one of the leading health threats
      worldwide, estimated to remain so at least by 2020, it is fully justified to
      invest all efforts in the study of cardiovascular disease. New research projects
      should be focused on the prevention and early detection of the disease,
      improvement of diagnosis procedures, introduction of novel therapeutic options,
      use of new concepts, and due survey of the measures taken. CHD poses great
      socioeconomic burden upon every community in industrialized societies because of
      the ever younger age at onset. Actions should be taken to improve awareness of
      the CHD risks and morbidity in the population at large, stimulating favorable
      lifestyle and dietary modifications, and one's own health awareness, in order to
      upgrade the control of risk factors for and morbidity of cardiovascular disease.

PMID- 18041380
TI  - Atherosclerotic lesions of supra-aortic arteries in diabetic patients.
AB  - The aim of this prospective study was to determine the prevalence and
      localization of stenotic atherosclerotic lesions of supra-aortic arteries in
      diabetic patients according to age and sex. Angiograms obtained by digital
      subtraction angiography were analyzed in 150 diabetic patients (study group) and
      150 non-diabetic patients (control group) with symptoms of cerebral ischemia.
      Diabetic patients were found to have a significantly higher prevalence of
      stenotic atherosclerotic lesions of the internal carotid artery. Lesions of the
      large supra-aortic arteries were significantly more common in the left than in
      the right side of the neck (p < 0.001), but the difference between the diabetic
      and the non-diabetic group did not reach statistical significance. Hemodynamic
      conditions were found to be more important than diabetes for the occurrence of
      atherosclerotic lesions in these arteries. Changes in the proximal segment of the
      left common carotid artery were the most common finding in diabetic patients,
      hence attention should be paid to this localization on control examinations.

PMID- 18041381
TI  - Somatotype in elderly type 2 diabetes patients.
AB  - Somatotyping is a practical technique for the description of physique.
      Individuals with Type 2 diabetes are characterized by physical peculiarities,
      such as overweight, obesity and a central pattern of body fat distribution.
      Somatotype applications to diabetes are limited. The objective of this study is
      to describe the somatotype of elderly type 2 diabetes patients. The sample
      consisted of 110 patients with type 2 diabetes (45 men, mean age 69.4 +/- 7.0
      years; 65 women, mean age 72.9 +/- 7.1 years). The pathological subjects were
      compared with a control group consisting of 280 healthy individuals (134 men,
      mean age 74.2 +/- 7.3 years; 146 women, mean age 74.9 +/- 7.4 years). The Heath
      Carter somatotype was applied. Diabetic men and women (mean somatotype,
      respectively: 6.8-5.6-0.6 and 8.6-6.4-0.2) presented significantly higher values
      of endomorphy than the controls (p = 0.043 in men, p = 0.003 in women); men also
      had a lower mesomorphic component (p = 0.000). The somatotype method revealed
      physical peculiarities in type 2 diabetes patients. The marked endomorphy in the
      pathological individuals can be related to general fatness, which is a well known
      disease risk factor. The somatotype appears to be a suitable technique for the
      assessment of physique in type 2 diabetes patients.

PMID- 18041382
TI  - Frequency of anticardiolipin, antinuclear and anti-beta2 glycoprotein I
      antibodies in children with epilepsy.
AB  - A high prevalence of epilepsies in specific immunological diseases suggests that
      the immune system may play a role in the pathogenesis of epilepsy or might be
      associated with it. In this study the frequency of anticardiolipin antibodies
      (aCL), antinuclear antibodies (ANA) and anti-beta2-glycoprotein I antibodies
      (anti-beta2-GPI) in 40 children with epilepsy and in 38 healthy subjects was
      determined. Positive aCL was found in 3 patients, and anti-beta2-GPI in 1
      patient. In control group they were negative. ANA antibodies were negative in
      both groups. Duration of epilepsy < 1 year was observed in all three patients
      with positive aCL. No statistically significant difference was found concerning
      the presence of these antibodies between patients and controls. There was no
      statistically significant correlation of age, sex, age at the onset of epilepsy,
      duration of epilepsy, type of epilepsy, seizure frequency or specific
      antiepileptic medications with the presence of any measured antibodies.

PMID- 18041383
TI  - Cross-sectional study of ocular optical components interactions in emmetropes.
AB  - Purpose of the paper was to evaluate ocular optical components (OOC) interactions
      in a large number of emmetropes. A cross-sectional study of 1,000 emmetropes,
      aged from 18-40 years, has been conducted. Complete ophthalmological examination,
      corneal radius (CR) measurement, keratometry and echobiometry of both eyes were
      performed. The highest correlation of OOC was that of axial length (Ax) with
      vitreal body (CV) on both eyes (r = 0.79 for the right eye (RE); r = 0.81 for the
      left eye (LE)). The axial length had a positive correlation with the anterior
      chamber depth (ACD) on both eyes as well, but the coefficient was very low (r =
      0.29 for the RE; r = 0.32 for the LE). The only negative correlation Ax had on
      both eyes was with the lens (L) (r = -0.17 for the RE; r = -0.19 for the LE).
      Keratometry of the horizontal (K1) and vertical meridian (K2) showed a negative
      correlation with CV and Ax on both eyes (for K1 r = -0.64 for CV r = -0.54 for
      Ax; for K2 r = -0.67 for CV r = -0.68 for Ax). CR had a positive correlation with
      Ax (r = 0.74) and CV (r = 0.79). It showed a negative correlation with L (r = 
      0.58). CV had a high, positive correlation with Ax (r = 0.72 for the RE; r = 0.75
      for the LE). The correlation with K1 and K2 was negative. Our study showed that
      the axial length, keratometry, corneal radius, lens thickness and vitreal body
      were the most important OOC that correlated with each other following a pattern
      in our group of emmetropes. They interacted in such a way that in the subjects
      with axial length above the average value, the vitreal body was longer but the
      lens was thinner and the cornea was of less power. This could explain at least
      one of the mechanisms of emmetropization.

PMID- 18041384
TI  - Contact allergy to special and standard allergens in patients with venous ulcers.
AB  - The aim of the study was to determine the prevalence of contact sensitivity in
      patients with leg ulcers, and possible difference in the rate of contact
      hypersensitivity to standard series of allergens used in patch testing, and to
      particular topical agents used in local therapy of leg ulcers in special series,
      patients with and without atopy. The study included 60 patients, 45 female and 15
      male, aged 37-85 (mean 68.37 female and 51.13 male), 30 of them with and 30
      without allergic contact dermatitis (ACD) of the leg (control group). The mean
      duration of leg ulceration was 5.62 years. The two groups of patients underwent
      testing to standard series allergens and target series allergens including
      mupirocin, bepanthene, silver sulfadiazine, chloramphenicol +
      clostridiopeptidase, betamethasone dipropionate, hydrocortisone +
      oxytetracycline, momethasone, alginate, hydrocolloid, lanolin, pyrogallol,
      Vaseline, permanganate, Rivanol, povidone-iodine, gentamicin, i.e. local agents
      most frequently used by the patients. Contact allergic hypersensitivity to
      standard series allergens was demonstrated in 25 patients with a total of 49
      positive reactions and a mean of 1.6 reactions per patient. Positive reactions
      were most commonly recorded to balsam of Peru, fragrance mix and neomycin
      sulfate. There were 12 positive reactions to target series allergens, mean 0.4
      reactions per patient. Forty-five positive reactions, mean 0.1 reactions per
      patient, were recorded in the control group. Positive reactions were most
      commonly demonstrated to corticosteroid ointments, lanolin and bepanthene. Study
      results did not confirm a statistically significantly higher rate of
      sensitization to particular topical agents frequently used in the treatment of
      patients with venous ulcers. Patch testing to standard and special series
      allergens should be performed in case of prolonged leg ulcer epithelization.

PMID- 18041385
TI  - Helicobacter pylori infection and coronary artery disease.
AB  - The aim of this investigation was to determine the seroprevalence of H. pylori in
      patients with coronary artery disease (CAD). Patients with coronary artery
      disease (n = 90) and control group (n = 90) were enrolled into this randomized,
      multi-centre study. CAD risk factors analyzed included age, male gender, diabetes
      mellitus, systemic hypertension, cigarette smoking, hypercholesterolemia and
      socioeconomic status. The results of this study showed a higher seroprevalence of
      Helicobacter pylori infection in patients with CAD compared to controls (78.8%
      versus 58.3%, p < 0.05). However, Helicobacter pylori seropositivity was not
      associated with coronary artery risk factors (smoking, body mass index, diabetes
      mellitus, hypertension, total cholesterol and socioeconomic status) either in the
      whole study population or in the patients and control subjects analyzed
      separately (P > 0.05). Further study are needed to clarify the precise role of
      Helicobacter pylori infection on the development of coronary artery disease.

PMID- 18041386
TI  - Gastric myoelectrical activity in a population of healthy Croatian subjects.
AB  - Myoelectrical activity of the stomach was estimated in healthy Croatian subjects
      using the latest multi-channel percutaneous electrogastrograph. The aim of the
      study was to determine normal values of gastric myoelectrical activity for the
      population of Croatia. The study included 120 healthy subjects of both sexes,
      various age groups, body mass index values, and mode of lead placement. The
      measurement was performed 60 min before and 60 min after test meal. The following
      parameters of gastric myoelectrical activity were analyzed: dominant frequency
      (DF, c/min); dominant frequency within normal range (DFNR, %); coefficient of
      variation for dominant frequency (CVDF); dominant strength (DS, mV); postprandial
      increase intensity in dominant strength (PPIIDS; %); bradygastria (c/min, %);
      tachygastria (c/min, %); and arrhythmia. DF for the study group as a whole was
      around 3 cpm, at the normal range midpoint, and all other parameters were within
      the normal limits. On postprandial measurement, the rate of arrhythmias showed a
      significant decline. Age was found to influence DF, CVDF and arrhythmia in
      preprandial but not in postprandial period, whereas sex influenced DF, DS and
      bradygastria in preprandial period, and DF, CVDF, PPIIDS and tachygastria in
      postprandial period. The mode of lead placement had no impact on the
      electrogastrographic parameters observed. The values of gastric myoelectrical
      activity recorded in healthy Croatian subjects were within the normal range of
      the values defined by previous studies across Europe.

PMID- 18041387
TI  - Predictive parameters of gestational diabetes mellitus.
AB  - Gestational diabetes mellitus is a carbohydrate intolerance recognized in
      pregnancy. The objective of this study was to determine the prevalence of
      gestational diabetes mellitus (GDM) of all deliveries at the University Hospital
      Rijeka, Croatia (34 997 deliveries over 10-year period) using 2-hour 75 g oral
      glucose tolerant test and to evaluate the impact of GDM on neonatal outcomes and
      mother's health. Gestational diabetes was diagnosed in 55 of 128 pregnant women
      with suspected glucose intolerance. Logistic regression analysis was used to
      examine the relationship between fasting plasma glucose, age, family history,
      body mass index, maternal weight gain, neonatal weight, neonatal head diameter
      and Apgar score in the gestational diabetes group and in the non-diabetes group.
      The results indicate that fasting plasma glucose greater than 7.0 mmol/L and
      maternal overweight are strong predictors for GDM and macrosomia. There was no
      difference in the mode of delivery, and vitality and metabolic complications
      among the infants of all analyzed mothers. We concluded that to prevent GDM as
      well as to reduce the rate of macrosomic infants good glycemic control should be
      initiated as soon as possible. The 2-hour 75 g OGTT is worth enough to evaluate
      GDM. Women should be counseled and encouraged to lose weight before or at the
      beginning of the conception period.

PMID- 18041388
TI  - Stenotic occlusive lesions of internal carotid artery in diabetic patients.
AB  - Diabetes deteriorates atherosclerotic changes in the arteries. The aim of the
      study was to assess the prevalence and localization of stenotic atherosclerotic
      lesions of the internal carotid artery (ICA) in patients with diabetes. A
      prospective analysis of angiography findings was carried out in 150 diabetic and
      150 non-diabetic patients with symptoms of cerebral ischemia using double-blind
      angiogram readings by two independent investigators. The degree of stenosis was
      determined using the North American Symptomatic Carotid Endarterectomy Trial
      (NASCET) criteria. Stenoses of the proximal arterial segment accounted for the
      majority of extracranial ICA stenoses, being more frequent in diabetic (left ICA
      50.7%, right ICA 58.0%) than in the non-diabetic patients (left ICA 29.3%, right
      ICA 32.7%). Diabetic patients revealed a more significant rate of unilateral
      tandem ICA stenoses (14.0-21.3%), as well as a statistically significantly higher
      prevalence of intracranial ICA stenoses (left ICA 24.0% and right ICA 17.3%) than
      did non-diabetic patients (left and right ICA 3.3% each). Our results confirm
      that there is a morphological basis in ICA for increased incidence of ICA lesions
      in patients with diabetes as compared to those without it. Data on the incidence
      of stenotic ICA lesions in diabetes suggest the importance of assessing overall
      ICA status using digital subtraction angiography. Such an assessment is a
      precondition for an optimal therapeutic approach, especially in diabetic patients
      who are at an increased risk of cerebrovascular disease.

PMID- 18041389
TI  - The analysis of walk cycle in patients with spastic cerebral palsy after surgical
      management on the lower extremity.
AB  - Gait pattern is a frequent problem in cerebral palsy. The aim of the
      investigation is the evaluation of proximal femur normalization and/or pelvis
      normalization after surgical correction and simultaneous operations on soft
      tissues of lower limbs, as well as walk analysis. From 1980. to 2000. were
      operated 856 patients, 476 male and 380 female, between 1-51 years. Basic walk
      parameters were analyzed: step length, speed and the number of steps in one
      minute (cadence). 75.25% of patients had good results with improved of centrum
      collum diaphysis (CCD) and angle of anteversion (AV) or antetorsion (AT) for 70%,
      and more independent walking with contracture corrections and decreased
      spasticism. The best results were achieved with simultaneous two-side operations,
      with patients' age between 1 and 3, achieving independent walking. More
      operations at the same time significantly reduce spasticism--one anesthesia, one
      immobilization, and later same time post-operative physical therapy and
      satisfactory better results.

PMID- 18041390
TI  - Is agility related to strength qualities?--Analysis in latent space.
AB  - In this study we examined an influence of leg extensor strength qualities on
      agility performance in a latent space. Male physical education students (N = 168)
      were tested with three standard agility performance tests (lateral stepping, 20
      yard shuttle run, and slalom run). Nine measures of leg extensor strength
      qualities including explosive strength, elastic strength, and maximal strength,
      were also assessed. As expected, factor analysis of all tests revealed four
      relatively independent factors: explosive strength, elastic strength, agility,
      and maximal strength. All three extracted strength factors were included into a
      regression analysis as predictors to evaluate their influence of the agility
      factor (i.e. criterion). Although the regression analysis revealed significant
      multiple correlation between predictors and the criterion (R = 0.41; p < 0.001),
      the amount of explained variance of agility performance by the strength factors
      was rather low (17%). We conclude that the leg extensor strength qualities are
      poor predictors of agility performance in physically active men.

PMID- 18041391
TI  - Biomotor structures in elite female handball players.
AB  - In order to identify biomotor structures in elite female handball players, factor
      structures of morphological characteristics and basic motor abilities of elite
      female handball players (N = 53) were determined first, followed by determination
      of relations between the morphological-motor space factors obtained and the set
      of criterion variables evaluating situation motor abilities in handball. Factor
      analysis of 14 morphological measures produced three morphological factors, i.e.
      factor of absolute voluminosity (mesoendomorph), factor of longitudinal skeleton
      dimensionality, and factor of transverse hand dimensionality. Factor analysis of
      15 motor variables yielded five basic motor dimensions, i.e. factor of agility,
      factor of jumping explosive strength, factor of throwing explosive strength,
      factor of movement frequency rate, and factor of running explosive strength
      (sprint). Four significant canonic correlations, i.e. linear combinations,
      explained the correlation between the set of eight latent variables of the
      morphological and basic motor space and five variables of situation motoricity.
      First canonic linear combination is based on the positive effect of the factors
      of agility/coordination on the ability of fast movement without ball. Second
      linear combination is based on the effect of jumping explosive strength and
      transverse hand dimensionality on ball manipulation, throw precision, and speed
      of movement with ball. Third linear combination is based on the running explosive
      strength determination by the speed of movement with ball, whereas fourth
      combination is determined by throwing and jumping explosive strength, and agility
      on ball pass. The results obtained were consistent with the model of selection in
      female handball proposed (Srhoj et al., 2006), showing the speed of movement
      without ball and the ability of ball manipulation to be the predominant specific
      abilities, as indicated by the first and second linear combination.

PMID- 18041392
TI  - Non linear anthropometric predictors in swimming.
AB  - In this paper we have tried to identify the significance and character of the
      linear and non-linear relations between simple anthropometric predictors: body
      height (BH), body weight (BW), and body mass index, and swimming performance:
      freestyle swimming 50 (FS50) and 400 meters (FS400), in a sample of young (15
      years old on average) male (N = 40) and female (N = 28) swimmers. Linear (general
      model: y = a+bx) and nonlinear regression (general model: y = a+bx+cx2) were
      calculated simultaneously. Morphological variables are a significantly better
      predictor of the FS50 in males (BH mostly), and FS400 in females (BW mostly).
      This study emphasized some of the main advantages in the nonlinear regression
      calculation (including an interpretation of the relationships at a more superior
      level), and consequently allowed a precise anthropometric modeling in swimming
      using simple and easily measurable variables. For example, the best results in
      FS400 can be expected for the subjects that are average in BW (which guarantees
      solid muscle mass--the generator of force), but above average in BH (because of
      the physical law of lever). In conclusion, nonlinear regressions allow one to
      define the real nature of the relationships between variables, but only if
      compared with the linear ones. Additionally, this study emphasized one of the
      most important factors in defining possible specification-equation (e.g.
      structure of the influence of the different dimensions on the sport achievement)
      in different sports. In short, it underlines the importance of sampling the
      appropriate sample of the subject--highly skilled athletes exclusively.

PMID- 18041393
TI  - What distinguishes the Olympic level heavyweight rowers from other
      internationally successful rowers?
AB  - The aim of the study was to determine which of the observed variables
      differentiate mostly the successful (Olympic Games contenders) from the less
      successful rowers (Internationally competitive rowers) and in order for that
      anthropometric and physiological profile of elite Croatian heavyweight rowers was
      assessed. Twenty nine national rowing champions were divided into two groups
      according to their international competitive achievements. Physiological
      characteristics were assessed during a continuous progressive rowing ergometer
      test. Differences were determined using the independent t-test with Bonferroni
      corrections. Successful rowers had somewhat larger values of almost all of the
      observed lengths, widths and girths (exceptions: chest and thigh girth). In
      addition, their maximal oxygen uptake was significantly higher (5.51 +/- 0.40
      L/min vs. 5.16 +/- 0.39 L/min; p < 0.05) as was their power output at anaerobic
      threshold (346.3 +/-17.9 W vs. 319.2 +/- 20.1 W; p < 0.01). Less successful
      Croatian rowers should target their training in the upcoming years towards
      increasing, primarily, maximal oxygen uptake and power output at anaerobic
      threshold.

PMID- 18041394
TI  - Motor abilities at belly dance in elementary female schoolers.
AB  - The aim of the study was to determine the relation between motor abilities and
      belly dance performance in elementary school fifth- and sixth-grade female
      students. A battery of 19 motor tests was used in a sample of 96 students twice,
      i.e. at the beginning (initial measurement) and at the end (final measurement) of
      the academic year. On initial measurement, five factors were isolated by the
      motor space factor analysis: first factor of muscular-aerobic endurance; second
      factor integrating the strength of legs, coordination of foot and hand movement,
      and agility; third factor integrating explosive strength of the arms with speed
      and body coordination; fourth factor defined by flexibility (muscle tone
      regulation); and fifth factor integrating explosive strength of legs with
      equilibrium. On final measurement, five factors were isolated as well: first
      factor as a general one integrating coordination abilities, explosive strength of
      legs and flexibility; second factor defined by repetitive strength of the trunk
      and legs; third factor defined by rhythm coordination accompanied by flexibility;
      fourth factor predominantly defined by equilibrium (accompanied by explosive
      strength of throwing type and speed); and fifth factor predominantly defined by
      static strength of arms and legs (accompanied by arm movement frequency). On
      initial measurement, fourth factor responsible for muscle tone regulation and
      second factor integrating the strength of legs, coordination of movement
      frequency of arms and legs, and agility were found to be the best predictors of
      belly dance performance. In this setting, the tests of forward bow (flexibility)
      and sit-ups (repetitive strength of abdominal musculature) proved superior in
      differentiating high performance students and those less successful in belly
      dance. On final measurement, third factor named rhythm coordination (accompanied
      by muscle tone regulation) and second factor defined by repetitive strength of
      the trunk and legs were the best predictors of belly dance performance. In this
      setting, the tests of rhythm coordination, flexibility tests, tests of repetitive
      strength of the trunk and legs, and test of aerobic endurance proved superior in
      differentiating high performance and less successful students in belly dance.

PMID- 18041395
TI  - Impairment of proprioception after whiplash injury.
AB  - Whiplash injury usually occurs in traffic accidents. Persons experienced this
      injury might have an impairment of proprioception clinically expressed as
      inability to determine the exact position of their heads. The aim of this study
      was to examine the loss of proprioception in people who had a whiplash injury.
      The study included 60 subjects with cervical spine injury, aged 20 to 50 years
      and 60 healthy volunteers matched by sex and age. The instrument used for
      cervical spine mobility assessment was the Cervical Measurement System (CMS),
      which determines the ability of subjects to return their head in the exact
      position as it was before they turned it 30 degrees left or right. Patients with
      cervical spine injury showed significant impairment of proprioception in
      comparison with healthy subjects (P < 0.001). The results support the hypothesis
      that subject with recent cervical spine injury have incorrect perception of their
      head position. Therefore, their rehabilitation should include the correction of
      proprioception and head coordination.

PMID- 18041396
TI  - Pulmonary compliance values provide prognosis in mechanically ventilated patients
      -a randomized prospective study.
AB  - Our aim was to evaluate the influence of static pulmonary compliance (Cst) on the
      choice of Mechanical Ventilation(MV) method and treatment outcome. A prospective,
      randomized trial conducted out at the multidisciplinary Intensive Care Unit (ICU)
      included 387 patients, randomized in two groups: noninvasive MV group and
      invasive MV group. Furthermore, each group was divided in two groups: Cst < or =
      0.025 and Cst > 0.025 L/cm H2O. In patients with Cst > 0.025 L/cm H2O MV
      duration, noninvasive vs invasive, was 92 vs 114 h, p = 0.039, time spent in ICU
      118 vs 164 h, p = 0.004. In patients with Cst < or = 0.025, MV duration was 141
      vs 189 h, p < 0.001, time spent in ICU 190 vs 246 h, p = 0.001, all patients were
      intubated. Need for tracheostomy was 6 (11%) vs 39 (46%) patients, p = 0.005, and
      ICU mortality was 15 (26%) vs 21 (25%) patients. Statistical significance in
      favor of noninvasive method was confirmed in patients with Cst > 0.025 L/cm H2O
      in MV duration, time spent in ICU, need for tracheostomy and intubation rate. In
      the group with Cst < or = 0.025 no significant difference in treatment failure
      was recorded between the two MV methods.

PMID- 18041397
TI  - Evaluation of DNA damage in radiotherapy-treated cancer patients using the
      alkaline comet assay.
AB  - The aim of this study was to evaluate primary DNA damage and the dynamics of the
      repair of radiotherapy-induced DNA lesions in non-target cells of cancer
      patients. This study included patients diagnosed with different solid tumors who
      received radiotherapy. The levels of DNA damage were evaluated using the alkaline
      comet assay on peripheral blood leukocytes. Altogether four blood samples per
      patient were collected: before and after receiving the first dose of
      radiotherapy, in the middle of radiotherapy cycle, and after the last dose of
      radiotherapy. The results indicate that after the first radiation dose
      significantly increased levels of DNA damage were recorded in almost all cancer
      patients compared to their baseline values. Specific patterns of DNA damage were
      recorded in samples analyzed in the middle of radiotherapy and after receiving
      the last dose, indicating the possibility of adaptive response in some patients.
      Our results indicate that persistence of post-irradiation damage in peripheral
      blood leukocytes (and possibly in other non-target cells) of cancer patients that
      are strong determinants for the secondary cancer risk. Moreover, the alkaline
      comet assay was confirmed as a rapid and sensitive assay for the assessment of
      genome damage after in vivo irradiation.

PMID- 18041398
TI  - Genetic diversity of 15 STR loci in a population of Montenegro.
AB  - Genetic diversity and forensic parameters based on 15AmpFlSTR Identifiler short
      tandem repeat (STR) loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01,
      D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) were
      evaluated in a sample of 101 unrelated, autochthonous adults from Montenegro.
      After applying Bonferroni correction, the agreement with Hardy-Weinberg
      equilibrium (HWE) was confirmed for all loci with the exception of D5S818 (chi2
      test) and D21S11 (exact test). The combined power of discrimination (PD) and the
      combined power of exclusion (PE) for the 15 studied loci were
      0.9999999999999999844 and 0.99999382, respectively. According to measures of
      within-population genetic diversity, D2S1338, D18S51 and FGA may be considered as
      the most variable and most informative markers for forensic testing and
      population genetic analyses out of the 15 analysed loci in a population of
      Montenegro. D5S818 showed to be the least variable and together with TPOX, the
      least informative. Interpopulation comparisons were carried out and levels of
      genetic differentiation between population of Montenegro and five South-eastern
      European populations (Kosovo Albanians, Serbians from Vojvodina province,
      Macedonians, Bosnians and Croatians) were evaluated. The most differentiated
      population in relation to Montenegro is a population of Kosovo Albanians as
      suggested by both AMOVA and coefficients of genetic differentiation (F(ST) and
      R(ST)).

PMID- 18041399
TI  - HLA class II polymorphism in autochthonous population of Gorski kotar, Croatia.
AB  - The aim of this study was to examine frequencies and haplotypic associations of
      HLA class II alleles in autochthonous population of Gorski kotar (Croatia). HLA
      DRB1, -DQA1 and -DQB1 alleles were determined by DNA based PCR typing in 63
      unrelated inhabitants from Gorski kotar whose parents and ancestors were born and
      lived in tested area for at least over four generations. A total of 13 HLA-DRB1,
      12 DQA1 and 14 DQB1 alleles were identified. The most frequent HLA class II genes
      in Gorski kotar population are: HLA-DRB1*13 (af = 0.150), -DRB1*03 (af = 0.142), 
      DRB1*07 (af = 0.119), and -DRB1*11 (af = 0.119), HLA-DQA1*0501 (af = 0.278), 
      DQA1*0102 (af = 0.183), -DQA1*0201 (af = 0.127) and HLA-DQB1*0301 (af = 0.157), 
      DQB1*0201 (af = 0.139), -DQB1*0501 (af = 0.111). We have identified 24 HLA class
      II three-locus haplotypes. The most common haplotypes in Gorski kotar population
      are DRB1*03-DQA* 0501-DQB1*0201 (0.120), DRB1*11-DQA1*0501-DQB1*0301 (0.111) and
      DRB1*07-DQA1*0201-DQB1*0202 (0.094). The allelic frequencies and populations
      distance dendrogram revealed the closest relationships of Gorski kotar population
      with Slovenians, Germans, Hungarians and general Croatian population, which is
      the result of turbulent migrations within this microregion during history.

PMID- 18041400
TI  - Rapid prenatal diagnosis of numerical aberrations of chromosome 21 and 18 by PCR
      STR method.
AB  - In this study we reported the results for the first time of applying Polymerase
      Chain Reaction-Short Tandem Repeats (PCR-STR) method in the field of detection of
      aneuploidies for chromosomes 21 and 18 in Croatians. The aims of the study were:
      (I) validation of the diagnostic informativeness of 6 STR loci (D18S51, D18S858,
      D18S535, D21S1435, D21S1411, and D21S1414) in sample of 205 unrelated healthy
      individuals; (II) evaluation of diagnostic power of the PCR-STR method for those
      6 microsatellites; (III) establishment protocol for use STRs as routine method
      for rapid prenatal detection of trisomy 21 and 18. DNA samples were amplified by
      fluorescence-based PCR reaction, subjected to electrophoresis in automated laser
      fluorescence DNA sequencer (ALFexpress). Results of our study were: (I) all 6
      tested loci are informative (68-85% of heterozygous individuals); (II) comparison
      between PCR-STR method and conventional cytogenetics did not revealed any false
      positive or false negative results; (III) in prenatal screening of 105 samples of
      uncultured amniotic fluid 6 (5.7%) samples with chromosomal abnormalities were
      identified.

PMID- 18041401
TI  - Digit ratio (2D:4D) in Lithuania once and now: testing for sex differences,
      relations with eye and hair color, and a possible secular change.
AB  - The second-to-fourth digit ratio (2D:4D) is a sexually dimorphic somatic trait
      and has been proposed as a biomarker for the organizational, i.e., permanent,
      effects of prenatal testosterone on the human brain. Accordingly, recent research
      has related 2D:4D to a variety of sex-dependent, hormonally influenced traits and
      phenotypes. The geographical variation in typical 2D:4D is marked and presently
      poorly understood. This study presents the first investigation into the 2D:4D
      ratio in a Baltic country. A contemporary sample of 109 Lithuanian men and women
      was compared with data from a historical sample of 100 Lithuanian men and women,
      collected and published in the 1880s and rediscovered only now. The findings
      included the following lines of evidence: (i) seen in an international
      perspective, the average 2D:4D in Lithuania is low; (ii) there was a sex
      difference in 2D:4D in the expected direction in both samples; (iii) a previously
      adduced hypothesis of an association of lighter eye and hair color with higher,
      i.e., more feminized, 2D:4D received no support in both samples; and (iv) the
      average 2D:4D in the contemporary sample was higher than in the historical
      sample. In view of a hypothesized increase in 2D:4D in modern populations, owing
      to increased environmental levels of endocrine disruptors such as xenoestrogens,
      this latter finding appears to be of particular notice. However, because finger
      length measurement methods differed across the samples, it cannot be safely ruled
      out that the apparent time trend in Lithuanian 2D:4D in truth is an artifact. The
      puzzling geographical pattern seen in the 2D:4D ratio and the question of
      possible time trends therein deserve further investigations.

PMID- 18041402
TI  - The ecological aspect of ethnobotany and ethnopharmacology of population in
      Bosnia and Herzegovina.
AB  - This paper contains first systematical revision of the results on traditional use
      of wild medicinal and aromatic herbs on the territory of Bosnia and Herzegovina
      (B&H)--west of Balkan Peninsula; Southeast of Europe. There have been detected
      227 plants belonging to 71 different plant families, which are being used with
      ethno therapeutic purpose. Results were obtained by method of open ethno
      botanical interview which comprised 150 persons, whose average age was 63.
      Medicinal plants in ethno therapy are being used either in fresh, raw or dried
      condition. Different herbal parts, depending on period of vegetation season,
      sometimes even in winter, are basis for preparation of infusions (59%), decoct
      (19%), tinctures (4%). Especially original are balms known as Bosnian "mehlems",
      which are fresh cuted herbal parts mixed with lukewarm resin, raw cow butter or
      honey. In ethno therapy are mostly being used aerial plant organs. Majority of
      herbs is being used for treatment of illnesses of respiratory (22%),
      gastrointestinal (19%) and urinary and genital system (9%), for treatment of skin
      conditions (11%), as well as for nervous system and heart diseases (16%). The
      most original plants on the field of ethno pharmacology, comparing with ethno
      therapy practice of other regions, are as follows: Ballota nigra, Aesculus
      hippocastanum, Calluna vulgaris, Centaurea cyanus, Euphrasia rostkoviana,
      Geranium robertianum, Gentiana asclepiadea, Helichrysum italicum, Lycopodium
      clavatum, Marrubium vulgare, Nepeta cataria, Populus tremula, Ruta graveolens,
      Tamus communis, Teucrium montanum, T. chamaedrys, and endemic plants Gentiana
      lutea subsp. symphyandra, Teucrium arduini, Micromeria thymifolia, Satureja
      montana, S. subspicata, Rhamnus fallax and Viola elegantula. There haven't been
      noticed significant differences in the frequencies of medicinal plants use among
      different ethnical groups. But, it has been perceived that longer ethno
      therapeutic tradition possess inhabitants of sub- and Mediterranean areas, as
      well as inhabitants of the mountain areas of B&H, regardless their ethnicity.

PMID- 18041403
TI  - Physicians' strike and general mortality: Croatia's experience of 2003.
AB  - The aim of the study was to establish whether the physicians' strike, which took
      place in Croatia in 2003, had an impact on the mortality of the population.
      Mortality data from the National Bureau of Statistics relating to the strike
      period (15 January - 14 February 2003) were selected and compared with the
      previous and subsequent periods of the same duration in 2001, 2002 and 2004. Of
      the 52,575 deaths in 2003, Croatia recorded 4,682 (8.9%, 95% Confidence interval
      8.4-9.4) in the strike period from the 15th of January to the 14th of February
      2003 or 1.1 deaths per 1000. No deviations of the 15th of January to the 14th of
      February period's share of the death total in relation to other observation
      periods were noted. It is impossible to associate the strike based on the figures
      shown in this paper with either an increase or decrease in population mortality.

PMID- 18041404
TI  - Effects of 500-year mercury mining and milling on cancer incidence in the region
      of Idrija, Slovenia.
AB  - The aim of the study was to determine whether the 500-year of mercury mining and
      milling in the Idrija region in Slovenia and the resulting environmental
      pollution with mercury and smelting wastes containing radon, has caused an
      increased cancer risk of the inhabitants. The polluted and the non-polluted parts
      of the region were defined. Cancer incidence from the two regions was compared.
      Cancer incidence among miners was investigated separately. In the polluted area
      male and female cancer incidence was higher than in the non-polluted area. Miners
      had an excess of incidence of total cancer, of oral and pharyngeal cancers and of
      lung cancer. As indicated by multivariate analysis the increased risk of miners
      could be assigned to their smoking and alcohol drinking habits. Higher estimated
      cumulative exposure to inorganic mercury seems to contribute to their risk as
      well. Most of the excess cancer incidence of the population from the polluted
      area could be explained by an unhealthy life style. In the case of lung cancer
      radon exposure contributes to the increased risk as well. Therefore, a well
      planed health promotion program and further sanitation of old houses is proposed.

PMID- 18041405
TI  - Fundamental restoration of the Civic Hospital in Split (1866-1872).
AB  - The aim of this study was to investigate the progress of the fundamental
      restoration and enlargement of the Civic Hospital in Split between 1866 and 1872
      on the basis of the previously unexplored materials, such as Shorthand reports of
      the Dalmatian Parliament in Zadar kept in the Split University Library, and the
      archival documents about the completion of this renewal preserved in the State
      Archives in Zadar. The right author of the restoration project and the name of
      the building manager were found. The data of the renewal beginning were
      corrected. The findings showed that the renewal of the Civic Hospital in Split
      started after the decision of the Dalmatian Parliament about its enlargement and
      restoration on February 9, 1866, according to the project drafted by the
      Provincial director of the public buildings doctor Ivan Lucchini. On October 7,
      1871, the Dalmatian Parliament determined about the way for the continuation of
      these works. The complete restoration of the Civic Hospital in Split finished in
      1872. The study revealed the realization of longtime efforts for the enlargement
      of hospital capacity in Split. With this restoration and appropriate
      organizational structure, the Civic Hospital in Split could offer better
      treatment to the patients, parturient women and foundlings.

PMID- 18041406
TI  - Analysis of fibroblast growth factor influence on growth and developmental
      potential of rat foetuses in the in vitro culture model.
AB  - The fibroblast growth factor's (FGF) influence on the growth and differentiation
      of 8- and 9- day-old rat foetus has been studied, whereas foetuses were grown in
      an in vitro culture model. Proliferation was analysed by the expression of
      proliferating cell nuclear antigen (PCNA). It was established that the usage of
      FGF in the first period of the culture lowers the growth no matter the foetus age
      at the moment of culturing and no matter whether it is a medium with or without a
      serum. If FGF is applied in the second culture period, it also lowers the growth,
      however younger foetuses in the in vitro culture model are more sensible to FGF
      negative influence. When FGF was applied in a lower concentration the growth of
      whole foetuses was improved in the in vitro culture model, which shows that the
      FGF influence on growth depends on the concentration. Stereological analyses have
      been done and showed that, in the in vitro culture model, FGF has no influence on
      proliferating cartilage tissue, but it stimulates the survival of nervel tissue
      cells. It has been shown that the quantitative research of growth processes in
      cultivated foetuses can precisely be done by combining classic methods of
      measuring whole foetus diameters and analysing the expression of proliferating
      antigen.

PMID- 18041407
TI  - MTHFR C 677T mutation and 4G/5G PAI-1 polymorphism in patient with polycystic
      ovarian syndrome.
AB  - Combined oral contraceptives (Ocs) are the most commonly used androgen
      suppressors and the treatment of choice for menstrual dysfunction in women with
      polycystic ovarian syndrome (PCOs). Although OCs have remained popular due to
      their convenience and effectiveness, there have been continuing concerns about
      adverse effects. The OCs have long been known to incur and increased risk of
      venous thromboembolism especially in carriers of common inherited thromboembolic
      defects. Factor V Leiden, prothrombin factor G20210A polymorphism, MTHFR (C677T)
      mutation and 4G/5G polymorphism of the PAI-1 gene account for the majority of
      thromboembolic events in association with oral contraceptive use. The aim of the
      article is to present woman with unrecognized inherited thrombophilia who was
      treated with OCs due to PCOs signs.

PMID- 18041408
TI  - Regeneration of the skeleton by recombinant human bone morphogenetic proteins.
AB  - Recombinant human bone morphogenetic proteins (rhBMPs) have past a long journey
      in human orthopaedic surgery during the last 15 years. From the first reports of
      the use of rhBMPs in hostile environments such as critically-sized bone defects,
      avascular femoral head necrosis, unstable thoracolumbar vertebral fractures,
      instability between the atlas and axis due to rheumatoid arthritis; over the use
      for nonunions of long bones and the scaphoid, reconstructive and revision
      surgeries of the hip, acute fractures, allograft nonunions, congenital
      pseudarthrosis, and various approaches of lumbar and cervical spine fusions,
      rhBMPs overgrow to a safe and reliable device in the treatment of open tibial
      shaft fractures, nonunions of long bone fractures, anterior lumbar interbody
      fusion and revision posterolateral lumbar fusions. Systematic review of the
      published literature of rhBMPs is presented.

PMID- 18041409
TI  - Fetal biometry charts for normal pregnant women in northeastern Thailand.
AB  - OBJECTIVES: 1) To construct normal fetal biometry charts of fetal biparietal
      diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur
      length (FL) from 14 to 41 weeks of gestation in northeastern Thailand. 2) To
      compare the results with other studies. STUDY DESIGN: A cross sectional
      descriptive study. SETTING: Division of Fetal Diagnosis and Therapy, Department
      of Obstetrics and Gynecology, Faculty of Medicine, Srinagarind Hospital, Khon
      Kaen University. MATERIAL AND METHOD: The fetuses of 635 pregnant women with an
      uncomplicated singleton pregnancy between 14 and 41 weeks of gestation in
      northeastern Thailand from 1 October 2005 to 31 December 2006. All recruited
      pregnant women enrolled had an abdominal ultrasonography for fetal biometry and
      the results were compared with other studies using student's T distribution. MAIN
      OUTCOME MEASURES: Fetal biometry charts for normal pregnant women between 14 and
      41 weeks of gestation in northeastern Thailand. RESULTS: Six hundred and twenty
      eight normal fetuses from 635 pregnant women were measured for fetal biometry
      charts. The comparison of the presented charts with others was significantly
      larger than the North in all parameters (except AC), but was consistent to those
      from the South (only BPD and FL). However when the authors compared then with
      central Thailand and Western countries, there were only significant differences
      in some gestational ages. CONCLUSION: The authors established normal fetal
      biometry charts for northeastern Thai pregnant women that could be implemented in
      the population of this region.

PMID- 18041410
TI  - Experience on triple markers serum screening for Down's syndrome fetus in Hat
      Yai, Regional Hospital.
AB  - OBJECTIVES: To summarize the experience and evaluate the performance of the Hat
      Yai maternal serum screening (MSS) program. SETTING: The Hat Yai MSS program
      between 16 February 2003 and 11 March 2004. MATERIAL AND METHOD: The uptake of
      screening was 999 in 1,040 women (96.0%), between 14 to 20 weeks of gestation
      with the triple markers: Alpha-fetoprotein (AFP), human Chorionic Gonadotropin
      (hCG), and unconjugated Estriol (uE3) by Immulite chemiluminescent immunoassay
      system, Diagnostic Product Corporation (DPC). The risk cut-off for Down 's
      syndrome is one in 250 or greater, based on software for prenatal Down's syndrome
      risk calculation, by Prisca 3.5 DPC. RESULTS: There were 119 in 999 cases (11.9%)
      of the triple test positive. Amniocentesis had been performed on voluntary basis,
      and the uptake rate of amniocentesis following a positive Down's syndrome
      screening was 104 in 119 cases (87.3%). Based on clinical diagnosis of Down's
      syndrome in the newborns of non-amniocentesis mothers, assuming that normal
      looking babies were not Down's syndrome, the sensitivity (SENS), specificity
      (SPEC), positive predictive value (PPV), and negative predictive value (NPV) of
      all chromosomal abnormalities were 85.7%, 88.6%, 5.0%, and 99.8% respectively.
      The false positive rate was 113 in 992 cases (11.4%). Whereas, the SENS, SPEC,
      PPV and NPV of Down's syndrome were 100%, 88.4%, 3.4%, and 100% respectively. The
      false positive rate was 115 in 995 cases (11.6%). The mean level, median level,
      and multiple of median (MoM) of triple markers were demonstrated. CONCLUSION: The
      Down's syndrome screening is a systematic application of a test to identify
      subjects at increased risk of a specific disorder; of course it is not
      diagnostic, but to benefit making decision regarding further amniocentesis. The
      sensitivity of Prisca 3.5 software was satisfactory but false positive rate was
      remarkably high. It needs further standardization with adjusted MoM values.

PMID- 18041411
TI  - Impact of bottle feeding prohibition on exclusively breastfeeding.
AB  - OBJECTIVE: To compare the time of colostrum expression and quantity of breast
      milk between early postpartum women who practiced exclusively breastfeeding and
      who had combined breast and bottle feeding. MATERIAL AND METHOD: Seventy mothers
      who delivered term normal, singleton infants were voluntarily recruited during
      immediate postpartum period and allocated into two groups. Study group was 35
      mothers who practiced exclusively breastfeeding and 35 mothers who practiced
      combined breast and bottle feeding were control group. Expression of colostrum at
      12, 24, and 48 hours and quantity of breast milk at 48 hours after delivery were
      evaluated and compared between two groups. RESULTS: At 12 and 24 hours after
      delivery, 65.7% and 88.6% of study group had colostrum compared to 37.1% and
      68.6% in control group, respectively. The difference was significantly higher in
      study group. However, at 48 hours after delivery, there was no statistical
      difference in both groups. Quantity of breast milk at 48 hours after delivery was
      5 mL (2, 10) in the study group compared to 2 mL (0, 8) in the control group,
      which was significantly different. CONCLUSION: Exclusively breastfeeding since
      immediate postpartum significantly promote earlier expression of colostrum and
      higher quantity of breast milk.

PMID- 18041412
TI  - Outcomes of pregnancies complicated by systemic lupus erythematosus (SLE).
AB  - OBJECTIVE: To assess the outcomes of pregnancies complicated by systemic lupus
      erythematosus (SLE) and evaluate the clinical course of the disease during
      pregnancy. MATERIAL AND METHOD: The database of high-risk pregnancies between
      1995 and 2006 was prospectively collected and searched for pregnancies with SLE.
      The medical records were reviewed RESULTS: Sixty-eight pregnant women were
      identified during the period of the present study. Of 61 (89.7%) live births, 27
      (39.7%) had preterm delivery and 20 (29.4%) had fetal growth restriction. Mean
      gestational age was 35.6 +/- 4.2 weeks. Mean neonatal birth weight was 2322 +/-
      781 grams. There were seven (10.3%) perinatal deaths. Maternal SLE flares
      occurred in 20 (29.4%), seven in the first trimester, eight in the second
      trimester five in the third trimester, and none in the post partum period.
      Preeclampsia is the most common maternal complication (20.6%). There was a higher
      rate of flares if the pregnancy occurred while the disease was active. The
      predictor of poor pregnancies outcomes included flare-up of the disease, renal
      involvement, hypertension, and conception while the disease is active.
      CONCLUSION: Active SLE prior to pregnancy is associated with a less favorable
      maternal and fetal outcome. Hypertension increased the risk of fetal loss and
      adverse outcome.

PMID- 18041413
TI  - Pre-operative prediction of serum CA125 level in women with ovarian masses.
AB  - OBJECTIVE: To assess the accuracy of serum CA125 at the level of more than 35
      U/mL in predicting ovarian cancer using histopathology as a gold standard.
      MATERIAL AND METHOD: Blood samples were obtained from 120 women with ovarian
      masses scheduled for elective surgery at Siriraj Hospital between October 1, 2003
      and August 31, 2004 and sent for the assay of serum CA125 levels. RESULTS: Of the
      120 women enrolled, ovarian cancer was found in 59 cases (49.2%) and benign
      ovarian mass in 61 cases (50.8%). The sensitivity, specificity, and accuracy of
      serum CA125 at the cutoff level of 35 U/mL for prediction of ovarian cancer were
      83.1%, 39.3%, and 60.8%, respectively; with 57.0% positive predictive value,
      70.6% negative predictive value, 60.7% false positive rate, and 16.9% false
      negative rate. CONCLUSION: As stand-alone modality, serum CA125 of more than 35
      U/mL in predicting ovarian cancer revealed modest diagnostic accuracy. There is a
      need to be careful for false positive in women at reproductive age group and
      false negative results in early-stage disease or ovarian cancer with low level of
      serum CA125.

PMID- 18041414
TI  - The efficacy of lidocaine-prilocaine cream to reduce pain in genetic
      amniocentesis.
AB  - OBJECTIVE: Evaluate whether local anesthesia by lidocaine-prilocaine cream
      decreases maternal pain during mid-trimester genetic amniocentesis. MATERIAL AND
      METHOD: This randomized controlled study of mid-trimester genetic amniocentesis
      was conducted between 1 October 2006 and 30 April 2007. Pregnant women were
      randomized to receive lidocaine-prilocaine cream or placebo cream 30 minutes
      prior to amniocentesis. Patients, blinded to allocation, recorded anticipated and
      actual pain before and after the procedure. The visual analog score (VAS) was
      evaluated, using a 0-10 scale. RESULTS: One hundred and twenty women participated
      in the present study. Sixty women were randomized to lidocaine-prilocaine group.
      The two groups were similar with respect to clinical correlations and procedure
      characteristics. Anticipated pain was 6.1 +/- 2.0 in the lidocaine-prilocaine
      group and 6.3 +/- 2.3 in the placebo group (p = 0.61). Actual pain was 2.3 +/-
      2.2 in the lidocaine-prilocaine group and 2.9 +/- 2.5 in the placebo group (p =
      0. 16). CONCLUSION: Lidocaine-prilocaine cream does not decrease pain during mid
      trimester genetic amniocentesis.

PMID- 18041415
TI  - A comparative study of tar and betamethasone valerate in chronic plaque
      psoriasis: a study in Thailand.
AB  - OBJECTIVE: Evaluate and compare the efficacy, safety, and tolerability of coal
      tar (10% LCD, liquor carbonis detergens), with betamethasone valerate in the
      therapy of large plaque-type psoriasis. MATERIAL AND METHOD: Patients with
      stable, mild to moderate plaque psoriasis at the Department of Medicine, Lerdsin
      General Hospital, Bangkok, Thailand were randomized for treatment with either
      coal tar (10% LCD) cream or betamethasone valerate cream (0.1%). All patients
      entered a 2 week wash-out period followed by the creams being applied twice daily
      until completion at 6 weeks. The patient severity of psoriasis was assessed using
      the modified Psoriasis Area and Severity Index (PASI) score at baseline and after
      2, 4, and 6 weeks of treatment. RESULT: At the end of the trial, the mean
      reduction of the PASI score from baseline was 38.39% with the coal tar group and
      69.36% with the betamethasone valerate group. The mean percentage of the PASI
      score reduction was statistically significant in both groups but the
      betamethasone valerate group was significantly superior to the coal tar group.
      Both drugs' adverse effects were limited to mild irritation localized to the skin
      without systemic side effects. The Betamethasone valerate cream was safe,
      effective, and well-tolerated while the coal tar cream was described as messy,
      malodorous, and with a tendency to staining clothes. CONCLUSION: The
      investigator's overall assessment of the treatment response at completion of the
      trial demonstrated that the betamethasone valerate group achieved significantly
      greater clearance and marked improvement compared with the coal tar group.

PMID- 18041416
TI  - A predictive score for unfavorable outcome of acute asthma in the emergency room.
AB  - BACKGROUND: It is sometimes difficult to decide on a safe discharge of an acute
      asthmatic patient from the emergency room (ER). OBJECTIVE: To develop a
      predictive score for safe discharge of an acute asthmatic patient from the ER.
      MATERIAL AND METHOD: All adult asthmatic patients who visited the ER at
      Ramathibodi Hospital from January 2004 to August 2005 were recruited Vital signs,
      oxygen saturation, and severity factors were recorded. Salbutamol was nebulized
      initially and repeatedly if the peak expiratory flow rates (PEFR) were < 70%
      predicted or if unfavorable physical signs were seen. Systemic steroids were
      administered to those patients whose severity factors had been identified
      Patients were admitted if further treatments were needed after the 4th
      nebulization. An unfavorable outcome was defined as either hospital admission or
      relapse within 48 hours of the ER discharge. Univariate analysis of each variable
      was performed, followed by multivariate analysis of those with statistical
      significance. Predictive scores were derived from statistically significant
      factors at the cutoff point of receiver-operating curve that yielded the best
      area under the curve. RESULTS: There were 905 visits from 568 patients.
      Predictive factors included inability to lie down on presentation and wheezing or
      low PEFR after the last dose of bronchodilator. A comparison of score
      sensitivity, specificity, and predictive values, across different cutoffs
      indicated that a score of 2 predicted an unfavorable outcome. CONCLUSION: A
      predictive score based on three bedside parameters might be used for a safe
      discharge of asthma patients from the ER.

PMID- 18041417
TI  - Anxiety and depression in Thai epileptic patients.
AB  - OBJECTIVE: To study the prevalence of depression and anxiety in Thai epileptic
      patients at Songklanagarind Hospital, a tertiary care center in the South of
      Thailand. MATERIAL AND METHOD: One hundred and twenty six patients were included
      in the present study. A HADS questionnaire and demographics data were used for
      data collection in the present cross-sectional study. RESULTS: Thirty-nine
      percent of the respondents had anxiety and 20% had depression. Predictors of
      anxiety by univariate analysis were being female (p = 0.033) and seizure
      frequency (p = 0.001). Predictors of depression were seizure frequency (p =
      0.001) and a history of trauma associated with seizure activity (p = 0.005). Age,
      type of seizure, amount of medication, duration of disease, socioeconomic status,
      occupation, education level, and marital status were not predictors of depression
      or anxiety. CONCLUSION: There is a high prevalence of depression and anxiety in
      Thai epileptics. Risk factors for depression are seizure frequency and history of
      trauma while for anxiety they are gender and frequency of seizure.

PMID- 18041418
TI  - Combined clinical risk indices with quantitative ultrasound calcaneus measurement
      for identifying osteoporosis in Thai postmenopausal women.
AB  - OBJECTIVE: To examine the diagnostic performance of clinical risk indices
      combined with quantitative ultrasound calcaneus measurement (QUS) for identifying
      osteoporosis in Thai postmenopausal women. MATERIAL AND METHOD: The present study
      was designed as a cross-sectional investigation in 300 Thai women, aged between
      38 and 85 years (mean age: 58). Femoral neck bone mineral density (BMD) was
      measured by DXA (Hologic QDR-4500; Hologic, Bedford, MA, USA). A BMD T-scores <
      or = -2.5 was defined as "osteoporosis"; otherwise, "non-osteoporosis". QUS was
      measured by Achilles+ (GE Lunar, Madison, WI, USA) and converted to T-score. The
      OSTA and KKOS score was calculated for each woman using her age and weight Women
      with OSTA/KKOS scores < or = -1 and > -1 were classified as "high risk" and "low
      risk", respectively. RESULTS: Using DXA as the gold standard, the sensitivity of
      QUS to identify osteoporosis was lower than the sensitivity of OSTA/KKOS (60 vs.
      71/74%) but the specificity and PPV of QUS were higher than OSTA/KKOS. The
      sensitivity increased when using OSTA/KKOS combined with QUS to identify
      osteoporosis (approximately 87-89%) while the specificity, PPV and NPV were
      comparable with using clinical risk indices alone. The risk (odds ratio; OR) of
      osteoporosis when QUS T-score < or = -2.5 alone was 9.94 (95%CI: 4.74-20.87),
      which was higher than high risk by OSTA/KKOS alone (OR: 6.35, 95%CI: 2.99-13.47
      for OSTA and 8.15, 95%CI: 3.76-17.66 for KKOS). Furthermore, individuals were
      classified "high risk" from OSTA/KKOS with QUS T-score < or = -2.5SD, the risk of
      osteoporosis was increased (OR: 43.68, 95%CI: 13.89-137.36 and OR: 60.92, 95%CI:
      17.69-209.76 for OSTA and KKOS, respectively). CONCLUSION: Using the clinical
      risk indices combined with QUS could improve the accuracy of osteoporosis
      identification. This approach could be used in a primary care setting or
      community-based hospital where a DXA machine is not available.

PMID- 18041419
TI  - D-dimer and pulmonary arterial hypertension in systemic sclerosis.
AB  - BACKGROUND: Micro-vascular thrombus is a common pathological finding in pulmonary
      artery hypertension. The association between plasma D-dimer, a marker of thrombus
      formation, and pulmonary artery hypertension (PAH) in patients with systemic
      sclerosis is unknown. OBJECTIVE: To assess the correlation of the level of plasma
      D-dimer and pulmonary artery pressure in patients with systemic sclerosis.
      MATERIAL AND METHOD: One hundred and twenty nine patients with systemic sclerosis
      between 19 and 75 years of age (mean, 48 +/- 11.3) entered the study. Plasma D
      dimer was determined using immunoturbidimetric assay (D-dimer plus, Dade Behring
      Inc., Newark, USA). Pulmonary artery pressure was estimated by Doppler
      echocardiography. PAH was considered present if the Doppler echocardiography
      estimated right ventricular systolic pressure (RVSP) exceeded 36 mmHg. RESULTS:
      Forty-seven patients (36.4%) had PAH according to Doppler echocardiography
      including 32 (68.1 %) mild (RVSP, 36-45 mmHg), nine (19.1%) moderate (RVSP, 46-55
      mmHg), and six (12.8%) severe PAH (RVSP > or = 56 mmHg). No significant
      correlation was found between plasma D-dimer and RVSP (r = 0. 02, p = 0. 82).
      CONCLUSION: The present study demonstrated that the D-dimmer level is not
      associated with the level of pulmonary artery pressure in patients with systemic
      sclerosis, indicating that microvascular thrombosis may not play a significant
      role in the pathogenesis of PAH in patients with systemic sclerosis.

PMID- 18041420
TI  - Impact of a new guideline for central venous catheter care on sepsis in total
      parenteral nutrition: experience in Ramathibodi Hospital.
AB  - BACKGROUND: Total parenteral nutrition (TPN) is the essential treatment for
      hospitalized patients in whom normal enteral nutrition is inadequate or not
      feasible. However, TPN-related sepsis is the most serious and fatal complication
      of the treatment and the catheter is the most common cause of infection.
      Therefore, the Nutrition Support team in Ramathibodi Hospital has developed a new
      guideline for central venous catheter care for TPN patients and has used it for
      at least a year. OBJECTIVE: Survey the current incidence of TPN-related sepsis in
      the hospital, the predisposing factors of the TPN-related sepsis, and the
      pathogenic organisms of the sepsis. MATERIAL AND METHOD: Between July 1999 and
      February 2000, 52 TPN treatments (catheter count) in 40 surgical and medical
      patients were prospectively recruited. Microbiological studies were done in all
      cases of TPN-related sepsis. RESULTS: The incidence of TPN-related sepsis was 15%
      per catheter or 12.64/1000 catheter-days. Although no statistically significant
      predisposing factors were found for the sepsis, some factors such as
      postoperative TPN and short interval (< or = 2 days) for TPN line change (OR =
      3.33, 95% CI = 0.33-30.34) showed a higher risk for TPN-related sepsis. The most
      common pathogenic organisms were Coagulase-negative staphylococci, Candida
      albicans, and gram-negative bacteria. The organisms were found from hemoculture
      in septic patients and were well correlated with those found in the catheter
      line. Thus, the significant pathogenic role of Coagulase-negative staphylococci
      emphasizes the importance of aseptic technique during catheterization.
      CONCLUSION: The Ramathibodi guideline rendered support for a good policy to
      improve and standardize the TPN treatment. Along with a practical guideline, the
      well-trained and highly responsible personnel would also be crucial to avoid the
      infectious complications.

PMID- 18041421
TI  - Septic death in adults at Surin Hospital: an investigation of real-life clinical
      practice vs. empirical guidelines.
AB  - OBJECTIVE: To explore the cause of death from sepsis and to evaluate the hospital
      practice in septic patients. MATERIAL AND METHOD: A cross-sectional,
      retrospective study was conducted between October 2004 and September 2005, at
      Surin Hospital. The present study included 119 adults (> or = 15 year of age) who
      were admitted with community-acquired sepsis. RESULTS: According to the ACCP/SCCM
      definition, 85.7% of the patients had severe sepsis and up to 71.4% had septic
      shock. The overall hospital mortality was 73.9% for septic patients and 88.2% for
      patients in septic shock. The factors that were significantly associated with
      death from sepsis were age > or = 60 years, presence of co-morbidity, septic
      shock, organ dysfunctions > or = 3, and acidosis (HCO3 < 20 mEq/L). During
      hospitalization, 5.9% of patients received ICU care, 29.4% adequate fluid
      resuscitation, but none had been monitored for Svo2 or Scvo2, and 36.4% had more
      than a 1-hr delay in the administration of antibiotics. The main cause of death
      was refractory hypotension (77.3%), in which the amount of fluid therapy during
      initial resuscitation was significantly associated with the survival of septic
      shock. CONCLUSION: Septic shock is the most common cause of death in septic
      patients. Delayed and inadequate hemodynamic management, including a delay in the
      administration of antibiotics are the main problems in real-life clinical
      management of septic patients.

PMID- 18041422
TI  - Diagnosis and growth hormone (GH) therapy in children with GH deficiency:
      experience in King Chulalongkorn Memorial Hospital, Thailand.
AB  - BACKGROUND: Diagnosis of growth hormone deficiency (GHD) needs both clinical and
      biological aspects such as auxological data and GHprovocative tests, and active
      metabolites of GH including IGF-I and IGFBP-3. In GHD children, rhGH has been
      used worldwide with minimal serious side effects. The aims of the present study
      were to describe the experience in King Chulalongkorn Memorial Hospital regarding
      diagnosis and treatment with rhGH in GHD children. MATERIAL AND METHOD: Clinical
      data of 173 short children was retrospectively reviewed. Two GH provocative tests
      used in the present study were insulin tolerance test (ITT) and clonidine test.
      To make the diagnosis of GHD, the children had to fail both GH provocative tests
      (peak GH < 10 ng/ml). Baseline clinical data, IGF-I, and IGFBP-3 were compared
      between the group with true positive test and the group with false positive test.
      Thirty-five children with GHD, who had been treated with rhGH, were evaluated in
      terms of growth response, changes of IGF-I SDS and the relationship between these
      parameters. RESULTS: From the present study, ITT could diagnose GHD with true
      positive 57% and false positive 43% and clonidine could diagnose with true
      positive 67% and false positive 33%. Clinical data including chronological age,
      bone age, HtSDS, WtSDS, IGF-I SDS, and IGFBP-3 SDS were not different between the
      true positive and false positive group. rhGH with a mean dose of 29.3 +/- 4.6
      microg/kg/day increased height velocity (HV) from 3.9 +/- 2.5 to 9.3 +/- 2.5, 8.1
      +/- 1.5, 7.2 +/- 2.2, 6.8 +/- 2.2, 7.6 +/- 2.4, and 6.5 +/- 1.8 cm/yr after 6
      months, 1, 2, 3, 4, and 5 years after treatment, respectively. This also improved
      HtSDS during treatment and brought the HtSDS into the target range after 3 years
      of treatment. At the end of the first year of treatment, the difference of IGF-I
      SDS (DeltaIGF-I SDS) > or = 1 could predict a good response (DeltaHtSDS > or =
      0.5) with sensitivity of 88.9% and specificity of 60% respectively. At the end of
      the second year, DeltaIGF-I SDS > or = 1 could predict a good response with
      sensitivity and specificity of 100% and 29%, respectively. CONCLUSION: From the
      present study, the authors demonstrated the investigation and treatment practices
      of short children with GHD. The growth response is satisfactory even with a lower
      dose than suggested. In addition, measurement of IGF-I and IGFBP-3 cannot be used
      in diagnosing GHD but can predict the height outcome at least by the first 2
      years of the treatment. However long-term outcome need to be clarified.

PMID- 18041423
TI  - Plasma levels of nitric oxide in children with congenital heart disease and
      increased pulmonary blood flow.
AB  - BACKGROUND: Development of pulmonary hypertension commonly accompanies congenital
      heart disease; nitric oxide (NO) is evidently an important mediator of pulmonary
      vascular reactivity. OBJECTIVE: Investigate the effect of pulmonary hypertension
      (PH) associated with congenital heart disease on NO production. MATERIAL AND
      METHOD: The authors measured plasma levels of nitric oxide-related compounds in
      28 patients, aged 3 months to 12 years with congenital heart disease (CHD) and
      increased pulmonary blood flow. Blood samples were obtained during their cardiac
      catheterization. The subjects were subsequently divided into two groups, namely:
      group 1 CHD were those with left-to-right shunt; and group 2, CHD with right-to
      left shunt. RESULTS: Four patients had severe pulmonary hypertension (mean
      pulmonary arterial pressure > 60 mmHg). The total levels of NO-related compounds
      between the two groups were not statistically different as well as the levels in
      pre- and post-pulmonary artery. In patients with left-to-right shunt with mild to
      moderate pulmonary hypertension, the levels of total NO-related compounds were
      directly correlated with the level of pulmonary arterial pressure and pulmonary
      vascular resistance (r = 0.67; p-value < 0.05, and r = 0.75; p-value < 0.05).
      Additionally, in patients with severe pulmonary hypertension, the levels of total
      NO-related compounds decreased when compared to the levels in patients with mild
      to moderate pulmonary hypertension. CONCLUSION: The present results suggested
      that the hemodynamic status of the pulmonary circulation in congenital heart
      defect is at least partly correlated with the blood levels of nitric oxide.

PMID- 18041424
TI  - The etiology and outcome of cerebrovascular diseases in Northeastern Thai
      children.
AB  - OBJECTIVE: To review the etiology and outcome of cerebrovascular diseases among
      children in Northeastern Thailand. STUDY DESIGN: Retrospective, descriptive
      study. SETTING: Srinagarind Hospital, Khon Kaen, Thailand. MATERIAL AND METHOD:
      The authors studied 109 pediatric patients admitted between April 1995 and 2006.
      RESULTS: The mean age was 11.6 years and the male-to-female ratio was 1.06:1. The
      ages at onset ranged from 6 months to 15 years, while the most commonly affected
      age group were children between 10 and 15 years. The authors identified 74
      hemorrhagic strokes (65%) and 35 ischemic strokes (31%). The most common
      etiologic factor in hemorrhagic and ischemic strokes was arteriovenous
      malformations and cardiac diseases respectively. The five most common presenting
      symptoms were headache, alteration of consciousness, hemiparesis, vomiting, and
      seizures. The mortality rate was 22%. CONCLUSION: Knowledge of the etiologies and
      outcomes of cerebrovascular disease in children should improve diagnosis and
      management.

PMID- 18041425
TI  - Effectiveness of mouthpiece nebulization and nasal swab stick packing for topical
      anesthesia in awake fiberoptic nasotracheal intubation.
AB  - OBJECTIVE: To evaluate the effectiveness of using mouthpiece nebulization and
      nasal swab stick packing for topical anesthesia in awake fiberoptic nasotracheal
      intubation. MATERIAL AND METHOD: This was a prospective descriptive study of 30
      patients with ASA I-II who underwent elective surgery and suspected of difficult
      intubation between March 2004 and June 2006. After 2% lidocaine 5 ml was
      nebulizated in a micronebulizer using oxygen 10 L/min as a driving gas through a
      standard mouthpiece and 10% cocaine 1 ml on cotton swab-stick was applied to the
      selected nostril for 15 min, fiberoptic nasotracheal intubation was done while
      the patient was awake. If the patient had severe gag or cough reflex, 1%
      lidocaine 5 ml per each time could be injected through the working channel of the
      fiberoptic bronchoscope. The descriptive statistics were calculated by using SPSS
      version 11.0. RESULTS: The success rate of awake fiberoptic nasotracheal was
      100%. The mean duration of awake fiberoptic nasotracheal intubation was 119.0 +/-
      76.8 sec. The responses of the patient to instrumentation during 4 periods, i.e.:
      passing the endotracheal tube into the nose, passing the bronchoscope into the
      pharynx-larynx, passing the bronchoscope into the trachea-carina and passing the
      endotracheal tube into the trachea were, as follows: no response in about 53.3%,
      63.3%, 23.3%,and 13.3%; mild pain or reflex in about 46.7%, 10%, 70%, and 86.7%;
      moderate pain or reflex in about 0%, 3.3%, 6.7%, and 0%; and severe pain or
      reflex requiring more local anesthetic in about 0%, 23.3%, 0%, and 0%,
      respectively. Despite complete topical anesthesia in the majority of the
      patients, two patients required 5 ml more 1% lidocaine and five patients required
      10 mL more of the drug through the fiberoptic bronchoscope. There was no serious
      complication such as hypoxemia, arrhythmia. Twenty-four patients (80%) were
      satisfied with mouthpiece nebulization and nasal swab packing because they felt
      safe, did not have pain, and were comfortable; only three patients (10%) were
      dissatisfied because of numbness of the tongue and difficulty in swallowing; two
      patients (6.7%) had no comment; and one patient (3.3%) was unable to evaluate due
      to unplanned tracheostomy. CONCLUSION: In the present study technique of topical
      anesthesia using 2% lidocaine 5 mL mouthpiece nebulization and 10% cocaine 1 mL
      soaked nasal swab stick packing is useful and safe for awake fiberoptic
      nasotracheal intubation in patients with suspected difficult intubation. 76.7% of
      the patient did not require more local anesthesia and 80% were satisfied with
      this technique.

PMID- 18041426
TI  - Pediatric anesthesia adverse events: the Thai Anesthesia Incidents Study (THAI
      Study) database of 25,098 cases.
AB  - BACKGROUND: The Thai Anesthesia Incidents Study (THAI Study) is the first
      national study of anesthesia outcomes during anesthesia practice in Thailand. The
      authors extracted data of 25,098 pediatric cases from THAI Study. OBJECTIVE: To
      report patient, surgical, and anesthetic profiles in order to determine the
      incidences of adverse events and their related factors. MATERIAL AND METHOD: A
      multi-centered prospective descriptive study was conducted among 20 hospitals
      across Thailand over a year from March 1, 2003 to February 28, 2004. Data in
      children aged 15 years and younger describing practices and adverse events were
      collected during anesthesia, in the recovery room and 24 hours postoperative
      period. RESULTS: Infants (0-1 year) had a significantly higher rate of adverse
      events compared with adults (4.6% versus 1.2%). Desaturation was the most common
      adverse event. The adverse events happened mostly during anesthesia (67%).
      Infants had significantly higher incidences of delayed detection of esophageal
      intubation, desaturation, reintubation, cardiac arrest, death, and drug error
      than older children and adults. Incidences of desaturation, reintubation,
      difficult intubation, coma/convulsion, cardiac arrest, and death were
      significantly higher in children with ASA physical status 3-5 than those with ASA
      physical status 1-2. CONCLUSION: Infants are prone to higher adverse events
      compared with older children and adults. Main adverse events were respiratory
      related and they occurred mostly during anesthesia.

PMID- 18041427
TI  - Endovascular abdominal aortic aneurysm repair in high risk patients: outcomes of
      management.
AB  - BACKGROUND: The concomitant cardiopulmonary disease precluded the elective repair
      for abdominal aortic aneurysm (AAA) with acceptable risk. The endovascular
      abdominal aortic aneurysm repair (EVAR) has become an alternative method for the
      treatment of AAA with high-risk comorbidities. OBJECTIVE: Evaluate the results of
      EVAR in high-risk patients with large AAA. MATERIAL AND METHOD: A prospective
      study of high-risk patients with large AAA and suitable morphology who underwent
      EVAR between August 2003 and August 2005 was conducted. The long-term outcomes
      were observed up to December 2006. The comorbidities, size of aneurysm, types of
      procedures, operative time, amount of blood loss and transfusion, length of
      postoperative stay in intensive care unit and hospital, postoperative
      complications and mortality were analyzed. RESULTS: Eight patients (7 males and 1
      female) with the mean age of 71.4 years (range 66-83 years) were included in the
      present study. The comorbidities were six of compromised cardiac status, one of
      severe pulmonary disease and one of morbid obesity. The average size of aneurysm
      was 6.2 +/- 0.64 centimetres. One patient also had large bilateral iliac artery
      aneurysms. Seven patients underwent EVAR with bifurcated aortic stent graft and
      one proceeded with aorto uni-iliac stent graft. Three patients underwent
      preoperative coil embolisation into internal iliac arteries when the distal
      landing zones at the external iliac arteries were considered. The mean estimated
      blood loss was 369cc and the mean blood transfusion was 0.88 units. There were no
      perioperative mortality, early graft occlusion, AAA rupture and open conversion
      in the present study. One patient had cardiac arrest due to upper airway
      obstruction but with successful treatment. Type II endoleak was observed in one
      patient and successfully treated by expectant management. One limb of bifurcated
      stent graft was occluded at the 5th month post EVAR and was successfully treated
      by artery bypass surgery at both groins. The 3-year primary graft limb patency
      was 87.5% (7/8). The survivals of patients at 1, 2 and 3 years were 100%, 100%
      and 87.5% respectively. The cause of death in one patient was not related to
      EVAR. CONCLUSION: EVAR may be a safe and effective alternative to open AAA repair
      especially in high-risk patients.

PMID- 18041428
TI  - Photodynamic therapy for AMD and non-AMD patients: one-year results in Thais.
AB  - OBJECTIVE: To evaluate the effect of photodynamic therapy (PDT) with verteporfin
      for age-related macular degeneration (AMD) and non-AMD in Thais, and compare with
      the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP)
      and Verteporfin in Photodynamic Therapy (VIP) study. MATERIAL AND METHOD: The
      authors prospectively evaluated all data of 51 eyes of 51 patients who had
      undergone PDT and accomplished a 1-year follow up. The assessments were divided
      into two categories: group 1 included three subsets of AMD, and group 2 was non
      AMD. The first group classified into three subgroups: group 1A: AMD with
      subfoveal choroidal neovascularization (CNV) and TAP/VIP compatible with
      recommendation guidelines characteristics, group 1B: AMD with subfoveal CNV and
      TAP/VIP incompatible, and group 1C: AMD with non-subfoveal CNV. The measurement
      outcomes comprised of the baseline characteristics, change in visual acuity, and
      number of treatments. RESULTS: Thirty-eight eyes had CNV-related AMD and 13 eyes
      were non-AMD. At the 12-month examination, the mean visual acuity change in group
      1A, 1B, 1C had increased 0.19 (p = 0.077), 0.14 (p = 0.076), and 0.24 (p =
      0.003), respectively. The number of treatments was 1.8 in group 1A, 2.3 in group
      1B, and 1.5 in group 1C. CONCLUSION: PDT is beneficial to Thai patients with AMD
      at first year even if they were not compatible with TAP/VIP criteria.

PMID- 18041429
TI  - Results of CO2 laser stapedotomy with Teflon piston prosthesis and autologous
      blood seal.
AB  - OBJECTIVE: To study the hearing results and complications in otosclerotic
      patients who underwent Carbon dioxide (CO2) laser stapedotomy using Teflon piston
      prosthesis and autologous blood seal. MATERIAL AND METHOD: The charts of all
      primary CO2 laser stapedotomy procedures performed at Bangkok Metropolitan
      Administration Medical College and Vajira Hospital between 1997 and 2005 were
      reviewed. Patients who used Teflon piston prosthesis and autologous blood seal
      and had follow-up data of more than one year were selected for inclusion in the
      study. Any patients who underwent CO2 laser stapedotomy for diseases other than
      otosclerosis or those with inadequate postoperative data were excluded. The
      hearing results from preoperative and postoperative (most recent follow-up)
      periods were analyzed using closure of air-bone gaps and postoperative
      sensorineural hearing loss (SNHL) at pure-tone average (PTA) and different
      frequencies. Major complications were recorded. RESULTS: The present review
      yielded 73 primary CO2 laser stapedotomy procedures performed between 1997 and
      2005, and 36 patients who underwent 40 CO2 laser stapedotomies met the criteria
      for analysis. The hearing outcomes were followed for an average of 22 months. The
      average preoperative and postoperative PTA air-bone gaps were 32.7 and 7.5 dB,
      respectively. The rate of patients who had postoperative PTA air-bone gaps within
      10 dB was 77.5% and within 15 dB was 95%. There was a significant closure of air
      bone gaps at PTA and at all frequencies (the frequencies from 0.5 to 4 kHz) and
      the closures of air-bone gaps at 0.5, 1, and 2 kHz were statistically better than
      at 4 kHz. The overall rate of postoperative SNHL was 7.5% at high pure-tone bone
      conduction average. There were no major postoperative complications. CONCLUSION:
      CO2 laser stapedotomy with Teflon piston prosthesis and autologous blood seal is
      a safe and effective treatment for otosclerosis. The procedure provides
      acceptable hearing results and gives the more air-bone gap closure at the low and
      mid frequency ranges without significant postoperative SNHL and other serious
      complications.

PMID- 18041430
TI  - Survival time of HIV-infected patients with cryptococcal meningitis.
AB  - OBJECTIVE: To study survival time and risk factors of mortality among HIV
      infected patients who had cryptococcal meningitis. DESIGN: Retrospective cohort
      study. MATERIAL AND METHOD: Patients' medical records of those who had HIV
      infection with newly diagnosed cryptoccocal meningitis between January 2002 and
      December 2004 were reviewed. Each patient was classified into one of two groups,
      according to their anti-retroviral status (ART). RESULTS: Five hundred and forty
      nine patients enrolled in the present study: 281 (51.2%) in the ART+ group and
      268 (48.8%) in the ART-group. The mean age was 33.4 +/- 6.9 years old in the ART
      + group and 33.6 +/- 7.0 years old in the ART-group. There were more male in both
      groups: 207 males and 74 females in the ART+ group, and 195 males and 73 females
      in the ART-group. Baseline CD4 cell count of both groups was 20 (6-74) cells/mL
      and 24 (9-72) cells/ml. About 30% of both groups of patients experienced major
      opportunistic infection before cryptococcal meningitis. All patients were treated
      by standard amphotericin B for a 2-week duration followed by fluconazole for an
      additional 8 weeks. There were no differences of baseline characteristics between
      the two groups (p > 0.05). The survival rates at 12, 24, and 36 months were
      92.8%, 87.4%, and 85.4% in the ART+ group and 55.3%, 42.2%, and 36.8% in the ART-
      group, respectively (p < 0.01). The median survival time in the ART- group was 15
      months. From the Cox regression model, the hazard ratio for "not received ART"
      was 4.87 (95%CI = 2.48-9.44, p < 0.01). CONCLUSION: The present study
      demonstrated the substantial increasing of survival time of HIV-infected patients
      with cryptococcal meningitis by initiated ART even in a resource limited setting
      (no flucytosine, local combined antiretroviral drugs with NVP based regimens).

PMID- 18041431
TI  - Abdominal manifestation and complications in systemic lupus erythematosus:
      emphasis on CT findings.
AB  - OBJECTIVE: To describe computed tomography (CT) features in SLE patients with
      suspected abdominal involvement or complications. MATERIAL AND METHOD: SLE
      Patients who presented with suspected abdominal involvement or complications and
      underwent CT between 2001 and 2005 were retrospectively reviewed. All CT studies
      were performed within 21 days of the onset of symptoms. RESULTS: Thirty-two SLE
      patients with 53 CT examinations including imaging findings and clinical data
      were reviewed. There were 29 cases with abdominal findings related to SLE
      including gastrointestinal vasculitis (6 cases), acute pancreatitis (8 cases),
      genitourinary abnormality (13 cases), hepatosplenomegaly, and ascites. Bowel wall
      thickening with target sign in CT is characteristics of GI vasculitis. Mild
      pancreatitis by CT scoring index was found in most cases. Five cases had diffuse
      bladder wall thickening and three cases also had bilateral hydronephrosis and
      hydroureter. Sixteen cases had other findings not related to SLE including bowel
      obstruction, splenic infarction, appendicitis, and hematoma. CONCLUSION: The
      common CT findings and complications in SLE patients who suspected abdominal
      involvement were presented CT is useful for detecting the primary cause of
      abdominal symptoms, planning treatment, and monitoring for complication.

PMID- 18041432
TI  - FOLFIRI chemotherapy for metastatic colorectal cancer patients.
AB  - OBJECTIVES: 1) To confirm the efficacy of irinotecan plus folinic acid/continuous
      5-fluorouracil as bimonthly FOLFIRI regimen in metastatic colorectal cancer
      patients. Efficacy evaluations will include response rate, duration of response,
      and survival. 2) To evaluate safety profiles on patients receiving this
      combination. MATERIAL AND METHOD: Nineteen patients with metastatic colorectal
      cancer received 180 mg/m2 intravenous (iv) day 1 of irinotecan, 200 mg/m2 iv of
      folinic acid, 400 mg/m2 iv bolus days 1 to 2, 5-fluorouracil (5-FU), and 600
      mg/m2 iv 5-FU infusion over 22 hours, days 1 to 2. Treatment was repeated every
      two weeks and one cycle contained three fortnightly administrations. Sites of
      disease were liver in nine patients, lungs in three patients, bowels in four
      patients, lymph nodes in three patients, and peritoneum in two patients. Two
      patients had > 1 metastatic site. Previous treatments included adjuvant
      chemotherapy in seven cases and front-line chemotherapy for advanced disease in
      one case. RESULTS: A median of six treatment cycles was completed (range, 2-13
      cycles). All patients were assessable for toxicity and 16 patients were evaluable
      for treatment response. The non-hematological toxicity was mild. Most had grade 1
      or 2. Only one patient experienced grade 3 fatigue and anorexia, and discontinued
      chemotherapy after the second cycle. There were no cases with grade 4 toxicity.
      Fourteen patients had at least grade 2 alopecia. The most common hematological
      toxicity was neutropenia. Grade 3 and 4 neutropenia were observed in three and
      two patients, respectively. There was no case of febrile neutropenia. Based on
      intention to treat analysis, there were no complete responses (CR), five (26.3%)
      partial response (PR), and 11 (57.9%) stable disease. With the median follow-up
      of 6.6 months, the median time to disease progression was 4.7 months and the
      median survival time was 10.6 months. CONCLUSION: Bimonthly irinotecan in
      combination with folinic acid and 5-fluorouracil was active with acceptable
      toxicities and a prolonged survival time in pretreated colorectal cancer.
      Additional trials to define the optimal dose and schedule of treatment are
      justified.

PMID- 18041433
TI  - The Sarcocystis-cyst containing beef and pork as the sources of natural
      intestinal sarcocystosis in Thai people.
AB  - BACKGROUND: Human intestinal sarcocystosis is a zoonotic disease caused by two
      coccidians, i.e. Sarcocystis fusiformis (syn. S. bovihominis, S. hominis) due to
      consumption of raw infected beef and Sarcocystis meischeriana (syn. S.
      suihominis) due to consumption of infected raw pork. In 1987, survey of the
      macroscopic S. fusiformis cysts in market beef mainly from old water buffalos
      aged more than 15 years were commonly observed in Bangkok. In 2005, the
      macroscopic cyst was no longer seen in beef of cattle and water buffalo aged less
      than three years. OBJECTIVE: The epidemiological investigation of Sarcocystis
      spp. infected meat in Bangkok and Lampang. MATERIAL AND METHOD: Samples for each
      of the tongue and beef of cattle and water buffalo, pork from Bangkok markets and
      pork of domestic swine from some remote villages in various subprovinces (Ampurs)
      in Lampang were obtained for microscopic examination by H and E and selectively
      by PAS staining. RESULTS: The microscopic S. fusiformis cysts were seen in all
      five specimens of tongues and ten specimens of muscles of cattle and water
      buffalo obtained from fresh-food markets in Bangkok. Ten samples of pork from
      Bangkok markets revealed no coccidian infection. The microscopic S. meischeriana
      cysts were seen in three specimens of swine muscles collected from two
      subprovinces in Lampang. CONCLUSION: The present merozoites in coccidian cysts
      retrieved from beef and pork are similar to those previously observed in human
      intestine. This may histologically indicate an invasive sarcocystosis by both
      species leading to a condition presently known as chronic inflammation of
      undetermined etiology in man.

PMID- 18041434
TI  - Binding of Leptospira to extracellular matrix proteins.
AB  - BACKGROUND: Leptospirosis is a zoonotic disease of global importance.
      Pathogenesis caused by this infectious disease remains unclear. Attachment of
      pathogenic leptospires to host tissues is a crucial initial step to establish the
      infection. OBJECTIVE: Study the binding of the spirochete to three types of
      extracellular matrix (ECM), collagen type IV, fibronectin, and laminin, which are
      major components of target organs. MATERIAL AND METHOD: ELISA-based experiments
      were performed to determine binding of pathogenic (serovar icterohaemorrhagie)
      and non-pathogenic (serovar Patoc) serovars, to purified ECM. RESULTS: Both
      pathogenic and non-pathogenic serovars bound to all three types of ECM in the
      dose-dependent manner and the binding to fibronectin is higher than to collagen
      and laminin (p < 0.005). CONCLUSION: Pathogenic leptospires can bind to various
      types of ECM and the binding of leptospires to fibronectin was higher than to
      collagen and laminin. However, this capability may not be the only mechanism that
      makes leptospires virulent since non-pathogenic leptospire can bind the ECM as
      well.

PMID- 18041435
TI  - Effects of combined sildenafil-nitric oxide donor on defibrillation efficacy.
AB  - BACKGROUND: A previous study demonstrated that supra-therapeutic concentration of
      sildenafil citrate attenuates defibrillation efficacy. However, the effect of
      combined sildenafil and NTG administration on defibrillation efficacy is not
      known. OBJECTIVE: The present study investigated whether sildenafil
      administration at the therapeutic level increases the defibrillation threshold
      (DFT) when combined with NTG. MATERIAL AND METHOD: Twenty-four pigs (20-25 kg)
      were randomized into four groups. After the control DFT was obtained, a stock
      solution of 50-mg (group 1, therapeutic concentration) and 100-mg (group 2,
      supratherapeutic concentration) of sildenafil, and 100-mL of saline (groups 3 and
      4) were infused at 2 mL/min. Then, NTG was administered in groups 1-3 at 5
      microg/min, with an increment of 5 microg/min every 5 min. The DFT was determined
      again after NTG was infused for 20 minutes. RESULTS: In group 1, the DFT (402 +/-
      33V, 11 +/- 2J) was not different from the control (404 +/- 28V, 11 +/- 2J). In
      group 2, the DFT (521 +/- 18V, 19 +/- 1J) was higher (p < 0.004) than that in the
      control group (444 +/- 31V, 14 +/- 2J). Saline did not alter the DFT either
      individually or in combination with NTG. CONCLUSION: Supratherapeutic dose of
      sildenafil-NTG combination significantly increased the DFT (17% of peak voltage,
      37% of total energy). This effect on DFT appears to be driven by sildenafil and
      not NTG.

PMID- 18041436
TI  - Glycemic and lipid responses to glucomannan in Thais with type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To evaluate the benefits of glucomannan supplement on glycemic and
      lipid controls in type 2 diabetic patients. MATERIAL AND METHOD: A single-blind,
      placebo-controlled, crossover trial with two treatments separated by a 2-week
      washout period was performed in 10 men and 10 women with type 2 diabetes
      mellitus. Two separated protocols of experiments were sequentially followed.
      Initially, purified glucomannan (1 g) or placebo was ingested 30 min before 75-g
      glucose load to evaluate their effects on glucose absorption and insulin
      secretion in oral glucose tolerance test (OGTT). Later, the glycemic and lipid
      changes after 4-week intervention with 3 g/day glucomannan comparing to the
      placebo were determined. The standard OGTT was performed before and after ending
      of each intervention. RESULTS: Glucomannan taken before performing the OGTT can
      lower the rise of blood glucose and insulin from 1 to 2 hour in comparison with
      the placebo, though a statistically significance of insulin was not achieved.
      Long-term glucomannan supplement significantly reduced the 120-min glucose area
      under the curve of OGTT. Glucomannan also decreased the rise of low-density
      lipoprotein cholesterol (LDL-C). Reductions of HOMA-insulin resistance index and
      body mass index were detected in glucomannan-treated group though the former was
      shown only in females. No within- and between-group differences of insulin,
      fructosamine, and other lipids were observed in glucomannan- nor placebo- treated
      groups. CONCLUSION: In type 2 diabetes, pre-prandial glucomannan ingestion
      attenuated a rise of blood glucose without significantly affecting insulin
      levels. Long-term supplement of glucomannan to the regular diabetic regimen
      lessened post challenge glucose AUC and impeded the rise of LDL-C. Supplement of
      glucomannan may be beneficial to the glycemic and lipid controls in type 2
      diabetes mellitus.

PMID- 18041437
TI  - An open-label study of quetiapine for delirium.
AB  - OBJECTIVE: To evaluate the effects of quetiapine treatment in patients with
      delirium. MATERIAL AND METHOD: All patients with delirium were assessed. The
      diagnosis of delirium was confirmed by using the Confusion Assessment Method
      (CAM). Quetiapine at the dose between 25 and 100 mg/day was given for 7 days. The
      efficacy of quetiapine on delirium was evaluated by using the Delirium Rating
      Scale (DRS) and the Clinical Global Impression-Severity scale (CGI-S). The
      extrapyramidal side effects were assessed by using the Modified (9-item) Simpson
      Angus Scale (MSAS). RESULTS: Twenty-two patients had delirium. Seventeen (10
      males and 7 females) subjects with a mean age (SD) of 55.6 (18.6) years were
      included in the present study. Means (SDs) dose and duration (SD) of quetiapine
      treatment were 45.7 (28.7) mg/day and 6.5 (2.0) days, respectively. The DRS and
      CGI-S scores of days 2-7 were significantly lower than those of day 0 (p < 0.
      001) for all comparisons). Only two subjects were shown to have mild tremor.
      CONCLUSION: Quetiapine within the range of 25-100 mg/day improves delirious
      condition within 24 hours of treatment. It is well-tolerated and has a very low
      propensity to induce extrapyramidal side effects. Further randomized, placebo
      controlled trials are warranted.

PMID- 18041438
TI  - Prevalence and psychosocial factors of anxiety and depression in breast cancer
      patients.
AB  - BACKGROUND: Breast cancer is the most common cancer in women. It is seen as a
      terrifying disease due to a high mortality rate, its impacts on self-image, and
      the sexual relationship. Many patients experience psychological reactions, and
      may have psychiatric morbidities, especially anxiety and depressive disorders.
      Although anxiety and depressive disorders are common in breast cancer and worsen
      the disease course and treatment outcomes, these psychiatric disorders are
      ignored and left untreated. Understanding these common psychiatric disorders and
      associated psychosocial factors can help to plan for treatment and may result in
      more treatment success. OBJECTIVES: The present study was aimed to identify the
      prevalence and associated psychosocial factors of anxiety and depressive
      disorders in breast cancer patients. The psychosocial factors in the present
      study focused on social support, family relationship and functioning, and problem
      and conflict solving. MATERIAL AND METHOD: Three hundred female breast cancer
      patients, aged above 18 years old from the Surgical Outpatient Department, King
      Chulalongkorn Memorial Hospital, were recruited into the study from December 2006
      to May 2007. All samples completed five questionnaires; 1) Demographic data and
      history form, 2) Thai Hospital Anxiety and Depression Scale (Thai HADS), 3)
      Social Support Questionnaire, 4) Family Relationship and Functioning
      Questionnaire, 5) Problem and Conflict Solving Questionnaire. The prevalence of
      anxiety and depressive disorders was reported in percentage. The association
      between psychosocial, demographic, and clinical factors and anxiety and
      depression was analyzed by ANOVA test (for continuous data) and chi-square test
      (for categorical data). Logistic regression was performed to identify the
      potential predictors of anxiety and depression. A p-value of less than 0.05 was
      considered statistically significant. RESULTS: The prevalence of anxiety disorder
      was 16.0%, and that of anxiety symptoms was 19.0%. The prevalence of depressive
      disorder was 9.0%, and that of depressive symptoms was 16.7%. Factors associated
      to anxiety and depression were psychosocial factors (social support, family
      relationship and functioning, and problem and conflict solving) (p < 0.01),
      number of hospital admissions, and presence of disturbing symptoms: pain,
      respiratory symptoms, and fatigue (p < 0.01). By regression analysis, the
      significant predictors of anxiety and depression were poor family relationship
      and functioning (p < 0.05), maladaptive problem and conflict solving (p < 0.05),
      and symptoms of pain (p < 0.01) and fatigue (p < 0.05). CONCLUSION: Anxiety and
      depressive disorders are two common psychiatric disorders in breast cancer.
      Strong predictors of anxiety and depression in breast cancer patients were poor
      family relationship and functioning, maladaptive problem and conflict solving,
      and presence of pain and fatigue. Promoting patients' social support, especially
      emotional support from family, and enhancing patient's coping skills may reduce
      the patients' psychological stress and psychiatric morbidities. Treatment of
      breast cancer patients should focus on reduction of patients' disturbing symptoms
      such as adequate pain control, and lessening the treatment complications.
      Moreover being alert on patients' emotional reactions and potential psychiatric
      disorders is essential.

PMID- 18041439
TI  - The incidence of clozapine-induced leukopenia in patients with schizophrenia at
      Srinagarind Hospital.
AB  - OBJECTIVE: Define the incidence of clozapine-induced leukopenia, neutropenia, and
      agranulocytosis in patients with schizophrenia at Srinagarind Hospital. MATERIAL
      AND METHOD: A descriptive study was done by retrospective reviews of the medical
      records of schizophrenic outpatients at psychiatric clinic in Srinagarind
      Hospital who had received clozapine from January 1st, 2003 to December 31st,
      2005. The demographic data, incidence rate, and incidence density of leukopenia,
      neutropenia, and agranulocytosis were collected. RESULTS: One hundred and
      seventeen medical records were reviewed, 65 patients met the inclusion criteria.
      One patient developed neutropenia. The incidence rate of neutropenia was 1.5% and
      the incidence density of neutropenia was 0.01/year. No leukopenia or
      agranulocytosis was found in the present study. The complete blood counts were
      not obtained regularly due to the problems of patient's adherence and variations
      in practice among the physicians. CONCLUSION: Neutropenia is uncommon. No
      leukopenia and agranulocytosis were found. According to variations of incidence
      reports among different studies, the monitoring of white blood count should be
      continued.

PMID- 18041440
TI  - An outbreak of imipenem-resistant Acinetobacter baumannii at Songklanagarind
      Hospital: the risk factors and patient prognosis.
AB  - OBJECTIVE: To investigate for the factors associated with acquisition of imipenem
      resistant Acinetobacter baumannii (IRAB) at Songklanagarind Hospital and the
      subsequent patient mortality outcome. DESIGN: A case-control study was conducted
      to evaluate the risk factors for IRAB acquisition using imipenem-sensitive A.
      baumannii (ISAB) as controls. A retrospective cohort study was employed to assess
      the factors associated with mortality in the hospital. SETTING: An 850-bed
      university hospital served as a medical school, training hospital, tertiary care,
      and referral center for the southern part of Thailand. PATIENTS: The patients who
      acquired A. baumannii during their stay in the hospital. RESULTS: Between July
      2003 and September 2005, there were 2,130 isolates of A. baumannii from clinical
      specimens of 1,237 hospitalized patients. The medical records of 899 admissions
      to the hospital were available for review. The significant risk factors
      associated with IRAB acquisition, identified from a case-control study and
      multiple logistic regression analysis included previous admission to medical
      surgical intensive care unit (ICU), respiratory care unit (RCU), previous use of
      multiple classes of antibiotics, and previous use of imipenem. The cohort study
      revealed that the mortality rate in the patients with IRAB compared to ISAB were
      33.8% and 24.1% respectively, yielding an unadjusted odds ratio of 1.6 (95% CI =
      1.2-2.2). However, after controlling for confounding factors by multivariate
      analysis IRAB did not show the increased mortality. CONCLUSION: The outbreak of
      IRAB at Songklanagarind Hospital is associated with increasing antibiotic
      pressure particularly imipenem and the admission to the ICU and RCU. The excess
      patient mortality rate attributable to IRAB is not significantly different from
      that attributable to ISAB.

PMID- 18041441
TI  - Disability assessment in elderly orthopedic patients.
AB  - OBJECTIVE: To assess the disability level in elderly patients with orthopedic
      conditions. MATERIAL AND METHOD: All possible patients aged more than 60 years,
      who attended the Out-patient Clinic of Orthopedic Department, Siriraj Hospital,
      between October and December 2005, were recruited. They were assessed for the
      disability level by using a Brief Disability Questionnaire (BDQ), Thai version.
      It is a simple and practical tool for assessing disability levels. It is an eight
      item scale with the total score ranging from 0 to 16. A higher score indicates a
      greater disability. RESULTS: Two hundred and thirteen patients participated in
      the study. The mean age was 69.4 years and 64% had degenerative joint diseases.
      The affected parts were the lower extremity and back (56.8% and 26.8%
      respectively). The three most common limited activities were vigorous activities,
      long distance walking, and stair climbing or walking uphill (55.9%, 51.6%, and
      42.7% respectively). The mean BDQ score of the subjects was 7.9 +/- 3.8. Patients
      with lower extremity problems including back problems had the highest BDQ score
      (8.2 +/- 3.7). According to the BDQ, the number of patients with a moderate-to
      severe degree of disability was 79%. CONCLUSION: The majority of elderly patients
      with orthopedic problems had moderate-to-severe disability as assessed by the
      BDQ. Physicians and other health care personnel should consider the management of
      the principal diseases, and the assessment of the disability level to improve the
      patients' quality of life, which is the ultimate goal of the treatment in
      clinical practice.

PMID- 18041442
TI  - Electrodiagnosis and recovery of facial paralysis at King Chulalongkorn Memorial
      Hospital.
AB  - OBJECTIVE: To study electrodiagnostic findings and recovery patterns of patients
      with facial nerve paralysis. MATERIAL AND METHOD: Seventy-six medical records of
      patients who had a facial paralysis and had their electrodiagnosis performed in a
      2-year period were reviewed. Patients were invited for re-evaluation. The
      patients would be evaluated according to House-Brackmann Facial Nerve Grading
      Scale (HBFNGS), residual impairment, disability, emotional and social
      consequences. RESULTS: Complete data were obtained from 50 patients whose mean
      age was 47.0 +/- 17.9 years. Seventy-two percent were diagnosed as Bell's palsy.
      There was significant correlation between %CMAP amplitude and HBFNGS (grade I-VI)
      at r = 0.5; p < 0.01. All cases of Bell's palsy with CMAP amplitude > or = 70% of
      normal side regained full recovery. Patients with CMAP amplitude > or = 30% had
      good recovery. Bell's palsy with CMAP amplitude < 10% and with other causes had
      poor outcome. Nine patients had synkinesis. Most of them were of traumatic cause
      and had severe nerve degeneration. No evidence showed that electrical stimulation
      was a factor inducing synkinesis. CONCLUSION: Percent CMAP amplitude could
      moderately predict the outcome of Bell's palsy better than other causes of facial
      palsy. The paralysis from traumatic cause with low %CMAP amplitude had more
      chance to develop synkinesis.

PMID- 18041443
TI  - A concurrence of light and heavy chain deposition disease and diabetic
      nephropathy.
AB  - A 56-year-old female patient was clinically characterized by heavy proteinuria,
      anemia, hypertension, and no detectable monoclonal protein in serum or urine. She
      had a history of diabetes with retinopathy and hypertension. Histological
      investigation of renal biopsy specimens revealed nodular glomerulosclerosis.
      Light microscopic examination did not allow discrimination between diabetic
      glomerulosclerosis and monoclonal immunoglobulin deposition disease (MIDD).
      Immunofluorescent examination showed linear capillary wall and tubular basement
      membrane staining with kappa, and IgG staining. Electron-microscopic examination
      confirmed the amorphous material along the glomerular basement. Based on these
      findings, the diagnosis of light chain and heavy chain monoclonal immunoglobulin
      deposition disease (LHCDD) and diabetic nephropathy was made. At the present
      after the 7th course of melphalan and prednisolone treatment, her renal function
      and proteinuria have progressively improved.

PMID- 18041444
TI  - Secondary vaginal involvement following radical surgical treatment for a stage I
      ovarian adenocarcinoma arising in mature cystic teratoma.
AB  - BACKGROUND: Vaginal carcinoma represents 1-2% of all gynecologic malignancies.
      Most cases reported secondary involvement from adjacent organs including cervix,
      uterus, and colorectum. Vaginal involvement from adenocarcinoma arising in mature
      cystic teratoma (MCT) has never been reported. CASE: A 29-year-old female
      presented with postcoital vaginal bleeding. She had had a history of right
      ovarian adenocarcinoma arising in MCT, FIGO stage IC, for 18 months' duration.
      Incisional biopsy of the vaginal lesion revealed adenocarcinoma, morphologically
      and immunohistologically identical to the right oophorectomized specimen. She
      received three courses of paclitaxel and carboplatin chemotherapy; however, she
      developed massive right pleural effusion with superior vena cava syndrome and
      finally succumbed to the disease, three months later. CONCLUSION: Adenocarcinoma
      is rarely found in MCT. This is the first case of ovarian adenocarcinoma arising
      in MCT with secondary vaginal involvement, presenting as postcoital vaginal
      bleeding.

PMID- 18041445
TI  - A Buddhist model for health care reform.
AB  - Although medical services are now available in every province in Thailand, there
      is ongoing discussion surrounding the question of how public health care should
      be best organized. There is much debate as to whether it should be run by private
      organizations in libertarian societies like that of the United States or whether
      it is the government that should be responsible for the welfare of all of its
      citizens equally, similar to that of the egalitarian system of socialist
      countries and welfare states. This article is aimed to answer the question: What
      is the most suitable model of health care system for Thailand? References are
      drawn from the Pali canon of the Theravada Buddhist tradition, articles,
      comments, and recommendations of contemporary thinkers in Thailand, to arrive at
      the most appropriate solution for the Thai society.

PMID- 18041446
TI  - Atypical dementia: when it is not Alzheimer's disease.
AB  - Dementia represents the most common neurodegenerative disorders affecting
      approximately 5% of the elderly population over age 65 years. At present,
      different forms of dementia are distinguished, including Alzheimer's disease
      (AD), dementia with Lewy bodies, frontotemporal dementia, and dementia secondary
      to diseases, such as AIDS dementia. Unlike AD, these atypical dementias are often
      associated with neurological symptoms, reflecting the localization of the
      degenerative process rather than the nature of the underlying histopathology. The
      present article provides an overview of the clinical evaluation of patients with
      atypical dementia and reviews distinguishing features of atypical dementias that
      may be confused with AD. The laboratory and imaging evaluation of various types
      of dementias are described. Current practice guidelines and practice parameters
      are reviewed as relevant for primary care practitioner.

PMID- 18041447
TI  - From embryonic stem cells to functioning germ cells: science, clinical and
      ethical perspectives.
AB  - Embryonic stem cells have been well recognized as cells having a versatile
      potential to differentiate into all types of cells in the body including germ
      cells. There are many research studies focusing on the differentiation processes
      and protocols to derive various types of somatic cells from embryonic stem cells.
      However, germ cells have unique differentiation process and developmental pathway
      compared with somatic cells. Consequently, they will require different
      differentiation protocols and special culture techniques. More understanding and
      established in vitro systems for gametogenesis will greatly contribute to further
      progression of knowledge and technology in germ cell biology, reproductive
      biology and reproductive medicine. Moreover if oocytes can be efficiently
      produced in vitro, this will play an important role on progression in nuclear
      transfer and nuclear reprogramming technology. The present article will provide
      concise review on past important discoveries, current ongoing studies and future
      views of this challenging research area. An ethical perspective has also been
      proposed to give comprehensive summary and viewpoint for future clinical
      application.

PMID- 18041448
TI  - Fraud and deceit in published medical research.
AB  - Medical research casts a great impact on health of the entire human population so
      it must be conducted and publicized without dishonesty or bias. Any
      misrepresentation can have extremely serious consequences for patients and
      clinical practice. Unfortunately, fraud and deceit have increasingly been
      detected and have become a problem in today's research. They are falsification,
      fabrication, plagiarism, and deliberate use of inappropriate statistical
      analysis. It is sometimes difficult to differentiate fraud from incompetence,
      errors, bias, and misunderstanding. Many fraudulent articles are still
      undercover. The question is how to detect and prevent the fraud and deceit in
      medical research. In addition, the system of handling research misconduct is
      still lacking. Critical audit and inspection are required to diagnose it. There
      is no standard guideline to treat fraud. Prevention is the best way of treatment.
      This relies on research institutions, editors of journals, citing authors, and,
      most of all the researchers who must adhere strictly to medical professionalism,
      which is solely based on honesty and ethics to self-regulate and conduct only
      ethical and genuine research.

PMID- 18041449
TI  - Treatment of infantile spasms with sodium valproate followed by benzodiazepines.

PMID- 18041450
TI  - Adherence in patients on dialysis: strategies for success.
AB  - Adherence is a major problem in patients with chronic kidney disease. Patients
      can be nonadherent with different aspects of their treatment, which includes
      medications, treatment regimens, and dietary and fluid restrictions. Although
      many lessons have been learned from adherence research, the evidence of how to
      modify adherence is somewhat mixed. To minimize nonadherence, interventions need
      to focus on both patient factors and the extent to which relationships and system
      problems compromise the patient's ability to adhere to medication and treatment
      plans. There continues to be a tendency to focus on the patient as the reason for
      problems with adherence, ignoring other factors such as the patient-health care
      provider relationships and the health care system that surrounds the patient.
      These latter factors can have a considerable effect on adherence. The nurse can
      develop a strong relationship of support with the patient, identify barriers, and
      offer strategies to help patients improve adherence.

PMID- 18041451
TI  - Blood pump speed vs. actual or "compensated" blood flow rate.
AB  - Actual blood flow rate delivered by a dialysis machine is often less than what is
      prescribed The Gambro Phoenix machine calculates the actual blood flow rate,
      reporting it as "compensated" blood flow rate. This study compared two methods of
      setting the prescribed rate, using Kt/V to determine the effectiveness of each.
      Results verified that patients achieve a higher Kt/V when the prescribed blood
      flow rate is set as the compensated blood flow rate.

PMID- 18041452
TI  - Professional communications: publications and presentations.
AB  - This article, which appears as Chapter 7 in ANNA's new publication, Career
      Fulfillment in Nephrology Nursing: Your Guide to Professional Development (2nd
      edition), will look at professional communications, including publications and
      presentations. ANNA's new publication, edited by Carol M. Headley and released in
      September 2007, will provide focus-driven direction and can serve as your
      personal guide and mentor to career development. The goals of this chapter are
      to: (a) define the elements common to preparing presentations and publications;
      (b) present the essentials of developing and submitting a manuscript for
      publication, and (c) demonstrate the core elements of making successful
      presentations.

PMID- 18041453
TI  - Perceptions of adult patients on hemodialysis concerning choice among renal
      replacement therapies.
AB  - PURPOSE: The aim of this study was to explore what patients on hemodialysis
      perceive concerning choice among three types of renal replacement therapies:
      transplantation, hemodialysis, and peritoneal dialysis. METHOD: A qualitative
      phenomenological research design was employed in this exploratory, descriptive
      study. A convenience sample was recruited from two urban dialysis units in the
      southern part of the United States. The analysis was performed using Colaizzi's
      (1978) phenomenological technique. RESULTS: Two themes emerged from analysis:
      knowledge and choice. Participants perceived choice in their renal replacement
      therapies. The predominant theme reflected that most participants had knowledge
      about at least two of the three types of renal replacement therapies. CONCLUSION:
      The areas of choice among renal replacement therapies, education about all renal
      replacement therapies, and other dynamics that impact choice, need to be studied.
      Inquiry needs to remain treatment specific and include all renal replacement
      treatments available to the patient. Future studies should continue to
      investigate perceptions of choice, and no assumption should be made about whether
      patients undergoing hemodialysis are receiving information or education on all
      the options for renal replacement therapy. Additional research within this area
      will validate needs and concerns of these patients.

PMID- 18041454
TI  - ANNA 2007 membership survey results.

PMID- 18041455
TI  - Route of administration for erythropoiesis-stimulating agents: patient and
      nursing considerations.
AB  - Several clinical studies have indicated that compared with intravenous (IV)
      administration, subcutaneous (SC) administration of Epoetin alfa may result in a
      dose-sparing effect in patients on hemodialysis. However, data also indicate wide
      inter-patient variability in response, with many patients requiring the same or a
      higher dose following conversion to SC administration. Convenience favors IV
      administration of Epoetin alfa in patients on hemodialysis, and patient
      preferences and comfort should also be primary considerations. For patients who
      prefer SC injections, the nurse's coordination of the required dosing,
      administration, and operational factors is key to maintaining and improving
      anemia-related outcomes.

PMID- 18041456
TI  - Updating practices in an evolving IV iron and anemia environment: practical
      solutions.
AB  - The latest considerations in the management of iron-deficiency anemia in patients
      on hemodialysis have centered on the updated guidelines and recommendations
      issued by the National Kidney Foundation, with interest on appropriate hemoglobin
      and serum ferritin targets. With practices evolving in the anemia environment, it
      is necessary for nurses to stay informed of new evidence-based data and practical
      solutions to improve patient outcomes. This underscores the importance of a team
      approach to managing anemia and balanced therapy with intravenous iron and
      erythropoiesis-stimulating agents. A symposium held during the 2007 annual
      meeting of the American Nephrology Nurses' Association addressed these issues.
      This article is based on the presentations and discussions from that symposium.

PMID- 18041457
TI  - End of life issues and advance care planning in the elderly patient.
AB  - Mr. J. achieved the desired outcome that was the best for him and his family. It
      remains to be seen how his trial of dialysis will fare. To date he is doing well
      and has not been readmitted to the hospital. The shift in his opinion regarding
      what would be the best decision for him has been significant, an evolutionary
      process, and followed a predictable course. When presented early, in a non
      emotional situation, perhaps greater numbers of patients will have advance
      directives signed and in place when the decision to start or withdraw from
      dialysis are imminent. Recognizing that advance care planning is one facet of end
      of-life planning will remind the nurse to look at all of the components in
      designing a patient plan of care. Further, knowing that this is an evolutionary
      process and should be revisited frequently will enable the nurse to incorporate
      the understanding that palliative care/hospice should be offered with dialysis,
      instead of taking an either/or approach. The unique issues facing the older adult
      also need to be evaluated and discussed with the patient/family. An
      acknowledgement of co-morbid conditions, mental status, and ambulatory status
      will help guide the nurse in estimating the best possible outcome and success of
      initiation of treatment. Nephrology nurses need a constant reminder that patients
      can change their minds at any point. As the dialysis population and number of
      patients with CKD continue to grow, the nephrology nurse practitioner and
      nephrology community are obligated to revisit and evaluate the success of their
      personal implementation of the guidelines that have been so rigorously
      formulated.

PMID- 18041458
TI  - Palliative care in patients with CKD.

PMID- 18041459
TI  - Who should be diagnosing, prescribing, and managing depression in patients with
      ESRD?

PMID- 18041460
TI  - Fluid management in patients on hemodialysis.

PMID- 18041461
TI  - Getting to know you: a national view of acute renal care.
AB  - The American Nephrology Nurses' Association's (ANNA's) newest Special Interest
      Group (SIG) is Acute Care. This SIG recently developed a survey to obtain
      information about the practice areas from acute care ANNA members as there is a
      lack of data about this subset of nephrology nurses. The survey was designed to
      begin to explore the practice of acute care nurses and was distributed via e-mail
      to 1000 ANNA members who are registered acute care nephrology nurses. There were
      246 responses to the survey. While the tool was not developed and confirmed as a
      reliable and valid tool, it was a first attempt to describe this population of
      nephrology nurses. Results of this survey of acute care nurses were presented at
      the Acute Care SIG networking session during the ANNA National Symposium in
      Dallas, Texas in April, 2007 The presentation, "Getting to Know You: A National
      View of Acute Renal Care," was presented by Acute Care SIG Members' Mary Rose
      Kott, MS, RN, CNN; Sue Fallone, MS, RN, CNN; Helen Williams, BSN, RN, CNN;
      Maureen Craig, MS, RN, CNN, CCNS; Billie Axley, BSN, RN, CNN; and Michelle
      Krueger, BSN, RN, CNN. The results are highlighted here.

PMID- 18041462
TI  - [Occupational medicine faces new health challenges: the example of alcohol
      dependence].
AB  - The regulations for application of the legislation on control of alcohol
      consumption at the work place, which were published in the Gazzetta Ufficiale No.
      75, March 30, 2006, set the occupational physician a more challenging task, in
      addition to regular activities related to the prevention of the usual work
      related risk factors. The aim of the legislation, which was derived from and
      inspired by the European Alcohol Action Plan 2000-2005, drawn up by the European
      Office of the WHO, is to prevent alcohol abuse and its consequences, i.e.
      accidents and injuries to third parties, and to permit subjects with alcohol
      dependence to go on working. In this context, occupational physicians are asked
      to contribute to the early identification of subjects prone to alcohol abuse and
      assess whether alcohol-dependent subjects can return to work in conditions of
      safety for themselves and for other workers. Various problems arise for the
      achievement of these aims in practice, and concern confidentiality, ethical
      aspects, i.e. use of alcohol screening at hiring, integration of such tests with
      those used for monitoring conventional occupational exposures, interactions with
      exposures to other chemical products, just to mention the major issues. Due to
      these difficulties in the application of the new regulations, field trials become
      all the more important, since they offer the possibility of assessing efficacy
      and efficiency of the different approaches.

PMID- 18041463
TI  - [Epidemiology of alcohol intake and alcohol-related problems in Italy].
AB  - BACKGROUND AND OBJECTIVES: The alcohol-attributable mortality is a positive
      function of two quantities: the relative risk, which has a biological
      specificity, and the proportion of exposed, which has a temporal and geographic
      specificity. Unfortunately, only little knowledge is available on these
      quantities. METHODS: To estimate alcohol-attributable mortality we approached the
      problem by estimating: i) the prevalence of drinkers to various amounts of
      alcohol in the Italian population from 1970 to 1993; ii) the dose-response
      relation between alcohol consumption and risk of each alcohol-related condition
      through a meta-analytic approach; iii) the alcohol-attributable risks from 1970
      to 1993 by using the drinkers prevalence estimates and relative risks evaluated
      previously; iv) the proportion of deaths related to alcohol consumption in Italy
      for the same period. RESULTS: Decreasing averages of per capita alcohol
      consumption (-44%) were observed from 1970 to 1993. In the same period was
      observed a reduction of -80%, -51% e -15%, respectively for heavy
      drinkers'prevalence (>100 g/die), moderate drinkers'prevalence (more than 50
      g/die) and for drinkers'prevalence (any consumption). The greatest alcohol
      attributable risks were observed for hepatic cirrhosis and for upper digestive
      and respiratory tract cancers. Applying the alcohol-attributable fractions to all
      deaths of 1993 about 44000 (corresponding to the 8% of overall mortality) were
      attributable to alcohol and about 32000 deaths were attributable to moderate
      intake (< or =100 g/die). CONCLUSIONS: The main suggestion from this study is
      that the best strategy in preventing alcohol-related problems should consider as
      target the whole population.

PMID- 18041464
TI  - [Alcohol and disadaptive behavioural responses].
AB  - BACKGROUND AND OBJECTIVES: The knowledge of heavy drinking and dependence on
      working behaviour is known and reflect the general community opinion and
      therefore is known in its more general and/or extreme manifestations (weekend
      deaths, dementia, polineuropathies). Less known and rarely measured are alcohol
      effects in heavy drinkers who have a high level of tolerance and only show
      manifestations which for a long time can be considered normal or seen as
      subjective peculiarities. DISCUSSION AND CONCLUSIONS: It is only in presence of
      serious accidents or dependence reactions that the drinking habit becomes
      evident. Cognitive, visuomotor and memory functions as well as personal and
      social behaviour should be examined but, it also appears that not all
      psychological measures are adequate to show the presence of possible cognitive
      deficiencies or behavioural dysfunction due to the fact that compensation
      mechanism can buffer for a long time alcohol behavioural effects. Two examples
      are described, reaction time measures and memory profiles.

PMID- 18041465
TI  - [Occupational relevance of alcohol related neurological involvement].
AB  - BACKGROUND AND OBJECTIVES: Accidents and various degrees of impairment in working
      performances and abilities are strongly correlated to alcohol consumption, either
      of moderate or of severe degree. Accidents, in particular, have been investigated
      in population studies that strongly suggest a direct effect of alcohol on
      attention and executive functions as well as a relevant interference of drinking
      with the neurological functioning and with eventual subclinical dysfunction of
      individuals: epilepsy threshold, cardiovascular risk and previous events, sleep
      disorders; post-traumatic sequelae. DISCUSSION AND CONCLUSIONS: Impairment of
      cognitive function (and concomitant functional/structural brain damage) is
      characterized, in particular, by difficulties in abstract problem solving, visuo
      spatial and verbal learning, memory function, perceptual and motor skills,
      related to disruption of frontal, pontocerebellar and cerebellothalamocortical
      systems. These abilities should therefore be monitored in at-risk working
      populations in order to prevent work accidents and to address appropriate
      therapeutic and rehabilitative interventions.

PMID- 18041466
TI  - [CDT: a biological marker of alcohol abuse].
AB  - BACKGROUND: Laboratory tests may be useful tools in the identification of heavy
      drinkers, in identifying the etiological role of alcohol in the onset of the
      disease, and in monitoring changes in alcohol intake. OBJECTIVES: An ideal
      diagnostic marker of alcohol abuse should: be characterized by high specificity
      and sensitivity; show an high specific correlation with alcohol metabolism; be
      dependent on alcohol intake and have a relatively short half-life (t1/2) so as to
      be able to monitor abstinence periods. CONCLUSIONS: CDT (Carbohydrate-Deficient
      Transferrin) meets all these requirements and offers the physician a significant
      tool as a marker of chronic alcohol abuse. CDT can reveal a daily alcohol
      consumption of 50-80 g of ethanol, corresponding to a bottle of 11 degrees-13
      degrees wine, for two consecutive weeks, with normalization after two weeks of
      abstinence (t1/2 of CDT is 15 days). Compared with other more common alcohol
      abuse markers, such as GGT or MCK CDT is more specific and provides more detailed
      information.

PMID- 18041467
TI  - [Occupational physicians' new attributions and responsibilities].
AB  - BACKGROUND: With the introduction in Italy of the Law regarding alcohol abuse and
      addiction (Law No.125/01), new tasks and responsibilities were assigned to
      occupational physicians. This law establishes that in working activities with a
      high risk of industrial accidents, or which may cause a risk for the safety and
      health of others, workers are forbidden to consume alcoholic beverages during
      working hours. In addition, occupational physicians are asked to play a key role
      in testing workers for alcohol levels. In March 2006 a specific list of job
      titles was issued which makes the law effective. DISCUSSION AND CONCLUSIONS: The
      application of this law gives rise to various consequences and ambiguities, in
      particular for occupational physicians, mainly concerning the identification of
      workers with alcohol problems, the subsequent control of such workers, including
      proposals for valid rehabilitation programmes, and assessment of residual work
      fitness. All these aspects can, to some extent, produce conflicts between privacy
      rights and the need to ensure the health and safety of workers and third parties.
      A specific screening package is proposed for the identification of alcohol abuse
      as well as methods to overcome some of the constraints. Specific and effective
      guidelines need to be issued by scientific societies and health authorities.

PMID- 18041468
TI  - [Alcohol and work: ethical-deontological and medico-legal remark upon the recent
      set of rules].
AB  - BACKGROUND AND OBJECTIVES: The Disposition of the Permanent Conference for the
      relation among the State, the Regions and the Autonomous Provinces of Trento and
      Bolzano, published in Gazzetta Ufficiale n. 75 on the 30th March 2006 the list of
      high-risk occupations under the influence of alcohol, activating de facto a
      previous law (Legge n. 125, 3017 march 2001, "Legge quadro in materia di alcol e
      di problemi alcolcorrelati"). We here present some ethical-deontological and
      medical-juridical profiles on the contents of this law and some consideration
      about its application. RESULTS AND CONCLUSIONS: Particular attention is dedicated
      to deontological aspects about industrial safety rules and to medico-legal
      aspects about occupation under the influence of alcohol, with references to
      complex relations among worker's discretion right, employer's right to the
      protection of his own interests and qualified doctor's (or someone to him
      comparable) right to the respect for the deontological code, with regard to
      benefit recipient information before the medical treatment. Authors'purpose is to
      evidence critical points and interpretative ambiguities of a regulation lacking
      in its practical applications, to provide further proposals of consideration,
      available to revalue a thematic rich in questions and with a significant social
      impact.

PMID- 18041469
TI  - [Vigilance in application of law 125/2001 concerning alcohol and alcohol-related
      risk assessment in workplaces].
AB  - BACKGROUND AND OBJECTIVES: The prohibition of using, dispensing or distributing
      alcoholic drinks at workplaces involving an elevated risk of accidents (Art. 15 -
      Law 125/2001 "General policy concerning alcohol and alcohol- related problems")
      is consistent with the duties of employers and employees regulated by Decree
      626/94. The purpose of this rule of law is the health protection of workers and
      of any third party in the workplace. Alcohol-addiction in workers has to be
      considered as part of the risk assessment and, in the case of the hazardous
      activities identified in the law, the increase in risk due to alcohol consumption
      must also be considered RESULTS AND CONCLUSIONS: Along with the prohibition of
      dispensing or distributing alcoholic drinks at the workplace, companies can
      launch training and information campaigns on the adverse health effects resulting
      from by harmful and hazardous alcohol consumption in workplaces, which will be
      all the more effective if addressed to all workers and not only to the more
      exposed employees. In developing this activity, the company occupational health
      physician has a central role to play by giving assistance to employees, involving
      the management and cooperating with public institutions. The controlling body
      will promote, support and supervise this process. In particular, the local
      authorities for Occupational Health and Safety (PSAL), together with social
      partners, will encourage companies to start up projects for health protection,
      will facilitate cooperation with the Pathological Addiction Services (Ser. T),
      and will encourage the implementation of a network to facilitate occupational
      health physicians in analyzing accident risks and solving health problems related
      to alcohol abuse.

PMID- 18041470
TI  - [Alcohol and construction workers].
AB  - BACKGROUND AND OBJECTIVES: On the basis of the data drawn by national and
      international literature and the introduction of recent legislation concerning
      "alcohol and alcohol-related problems", we studied alcohol consumption and the
      consequences that alcohol abuse has on health, working ability, accidents and
      absenteeism in construction workers. METHODS: We studied alcohol consumption in
      two groups of building workers over different periods (1996-2000; 2006). In 142
      workers alcohol concentration was measured in expired air during the periodic
      health surveillance examination and during work on building sites. We also
      analyzed the relationship between declared alcohol consumption, accidents and
      absenteeism. RESULTS: Our study showed a reduction in the average consumption of
      alcohol over the last ten years but confirmed the role of alcohol-related
      diseases as a cause of work limitations or work disability. On the other hand,
      "breathalysing" demonstrated that alcohol consumption during pauses in work is
      still common. CONCLUSIONS: The results of this study confirm the correlation
      between frequency/seriousness of accidents, absenteeism and average consumption
      of alcohol.

PMID- 18041471
TI  - [Alcohol intake, complex ability and responsibility towards others: experience on
      a cohort of personnel employed to public transport services].
AB  - BACKGROUND: The excessive intake or the abuse of alcoholic substances represent
      an important hazard's source for the individual health and for the carrying out
      of any complex working activities, above all if characterized by elevated
      responsibility toward other people. In this context the recent Provision of 16
      March 2006 of the Permanent Lecture for the Relationships among the State the
      Regions and the Autonomous Provinces of Trento and Bolzano, has individualized
      bus driver among the activities or tasks of which is forbidden the assumption of
      alcoholic drinks at work and can performed alcoholic controls by the competent
      physician (art. 15 of the Law March 30 th 2001, n. 125). Within the normative
      considering the DM 23 February 1999 n. 88s (Rule bringing norms dealing about the
      check and the control of the physical and psycho-aptitude ability of the
      personnel employed to public transport services), we introduced experience
      growing up in the period from January 2005 to August 2006, on about 1500
      employees, for over 90% of men, employed in a public transport company of the
      Lombardy as bus driver or railwayman. METHODS: In order to assess driver's
      alcoholic abuse the analytical determination of carbohydrate-deficient
      transferring (CDT) has been used as a marker of alcohol intake. Within the visits
      of hiring in service (equal to 10% of the total one of the effected visits) the
      determination of the CDT has always been performed, while in revision visits
      (equal to 90% of the total one) this analytical determination has been performed
      only if possible alcohol abuse has been hypothesized by elevated values of gamma
      GT before the Provision March 16th 2006 (and eventually of MCV, AST and ALT) and
      of routine from April 2006. CONCLUSIONS: This experience on this large population
      has confirmed the importance of a careful behaviours of abuse monitoring in
      workers with high responsibility toward other people. The CDT values reflect high
      alcoholic consumption, while is poorly remarkable the contribution furnished by
      anamnestic questionnaire.

PMID- 18041472
TI  - [Interactions between alcohol and work exposure to chemical substances].
AB  - BACKGROUND AND OBJECTIVES: The quite diffused habit of a significant assumption
      of alcohol drinks, can interfere with the professional exposure to chemical
      substances. The interaction may result in increasing their toxicity and/or
      modifying the parameters of the biological monitoring. It may also act as a
      confounding factor, not only in epidemiologic researches but also at individual
      level when the assessment of the occupational exposure and/or the diagnosis of an
      occupational diseases, is under consideration. We review available references in
      the literature summarizing major scientific evidences. RESULTS: The interaction
      between the alcohol assumption and industrial chemicals may be toxicokinetic or
      toxicodynamic. Alcohol can interfere in the processes of biotransformation of
      xenobiotics and modify the doses and the effect indicators used for the
      biological monitoring, causing wrong interpretations of the results. The
      metabolism of ethanol can be altered by the exposures to toxic industrial
      materials, creating some clinical pictures of alcohol intolerance, like an
      "antabuse syndrome" or an "degreaser flush syndrome". Professional exposure to
      carbon sulfide or to dimethylformamides, trichloroethylene as well as to
      nitroglycerin and nitroglycole ethylenic can produce similar syndromes.
      Interactions are reported between alcohol and solvents: on toxicokinetic bases
      for methanol, isopropanol, glycol ether, trichloroethylene, methyl ethyl ketone
      and toluene; and on toxicodynamic bases for CNS. Also between alcohol and metals
      there can occur toxicokinetic interactions, like in the case of lead and mercury.
      Alcohol can also interfere with the biological monitoring of solvents, producing
      an over-estimation of the exposure. CONCLUSIONS: For the biological monitoring of
      reported chemical substances, it is suitable to evaluate the biologic indicators
      in the days in which there is not assumed alcohol. If this cannot be guaranteed,
      it is necessary to know at least the quantity of the alcohol consumed or at least
      if the subject is an alcohol abuser.

PMID- 18041473
TI  - [Alcohol and work: remaining sober and return to work].
AB  - BACKGROUND: One of the most complex alcohol-driven problems is the job loss and
      the subsequent attempts to return to a professional activity. METHODS: In order
      to better understand the issue, an epidemiologic investigation was carried out on
      a group of 162 alcoholics whilst hospitalised in a specialised clinic. RESULTS:
      The outcome shows the importance of remaining sober to keep or to be returned to
      one's own job. Unfortunately, local resources at hand, first of all joining an
      auto-mutual-help group, re still too little known and thus clearly underemployed.
      Therefore, an informative action within companies is highly desirable. Those
      alcoholics suffering from serious illnesses, especially mental ones represent a
      different issue. CONCLUSIONS: For these people a higher involvement of public
      authorities is desirable in creating protected job openings.

PMID- 18041474
TI  - Practical consequences of fatigue-related performance failures.

PMID- 18041475
TI  - Electrical coupling: novel mechanism for sleep-wake control.
AB  - STUDY OBJECTIVES: Recent evidence suggests that certain anesthetic agents
      decrease electrical coupling, whereas the stimulant modafinil appears to increase
      electrical coupling. We investigated the potential role of electrical coupling in
      2 reticular activating system sites, the subcoeruleus nucleus and in the
      pedunculopontine nucleus, which has been implicated in the modulation of arousal
      via ascending cholinergic activation of intralaminar thalamus and descending
      activation of the subcoeruleus nucleus to generate some of the signs of rapid eye
      movement sleep. DESIGN: We used 6- to 30-day-old rat pups to obtain brainstem
      slices to perform whole-cell patch-clamp recordings. MEASUREMENTS AND RESULTS:
      Recordings from single cells revealed the presence of spikelets, manifestations
      of action potentials in coupled cells, and of dye coupling of neurons in the
      pedunculopontine nucleus. Recordings in pairs of pedunculopontine nucleus and
      subcoeruleus nucleus neurons revealed that some of these were electrically
      coupled with coupling coefficients of approximately 2%. After blockade of fast
      synaptic transmission, the cholinergic agonist carbachol was found to induce
      rhythmic activity in pedunculopontine nucleus and subcoeruleus nucleus neurons,
      an effect eliminated by the gap junction blockers carbenoxolone or mefloquine.
      The stimulant modafinil was found to decrease resistance in neurons in the
      pedunculopontine nucleus and subcoeruleus nucleus after fast synaptic blockade,
      indicating that the effect may be due to increased coupling. CONCLUSIONS: The
      finding of electrical coupling in specific reticular activating system cell
      groups supports the concept that this underlying process behind specific
      neurotransmitter interactions modulates ensemble activity across cell populations
      to promote changes in sleep-wake state.

PMID- 18041476
TI  - Running promotes wakefulness and increases cataplexy in orexin knockout mice.
AB  - STUDY OBJECTIVE: People with narcolepsy and mice lacking orexin/hypocretin have
      disrupted sleep/wake behavior and reduced physical activity. Our objective was to
      identify physiologic mechanisms through which orexin deficiency reduces locomotor
      activity. DESIGN: We examined spontaneous wheel running activity and its
      relationship to sleep/wake behavior in wild type (WT) and orexin knockout (KO)
      mice. Additionally, given that physical activity promotes alertness, we also
      studied whether orexin deficiency reduces the wake-promoting effects of exercise.
      MEASUREMENTS AND RESULTS: Orexin KO mice ran 42% less than WT mice. Their ability
      to run appeared normal as they initiated running as often as WT mice and ran at
      normal speeds. However, their running bouts were considerably shorter, and they
      often had cataplexy or quick transitions into sleep after running. Wheel running
      increased the total amount of wakefulness in WT and orexin KO mice similarly,
      however, KO mice continued to have moderately fragmented sleep/wake behavior.
      Wheel running also doubled the amount of cataplexy by increasing the probability
      of transitioning into cataplexy. CONCLUSIONS: Orexin KO mice run significantly
      less than normal, likely due to sleepiness, imminent cataplexy, or a reduced
      motivation to run. Orexin is not required for the wake-promoting effects of wheel
      running given that both WT and KO mice had similar increases in wakefulness with
      running wheels. In addition, the clear increase in cataplexy with wheel running
      suggests the possibility that positive emotions or reward can trigger murine
      cataplexy, similar to that seen in people and dogs with narcolepsy.

PMID- 18041477
TI  - Circadian rhythms of melatonin, cortisol, and clock gene expression during
      simulated night shift work.
AB  - STUDY OBJECTIVES: The synchronization of peripheral circadian oscillators in
      humans living on atypical sleep/wake schedules is largely unknown. In this night
      shift work simulation, we evaluate clock gene expression in peripheral blood
      mononuclear cells (PBMCs) relative to reliable markers of the central circadian
      pacemaker. DESIGN: Participants were placed on a 10-hr delayed sleep/wake
      schedule simulating nighttime work followed by a daytime sleep episode. SETTING:
      Baseline, intermediate and final circadian evaluations were performed in the
      temporal isolation laboratory. PARTICIPANTS: Five healthy candidates, 18-30
      years. INTERVENTIONS: Polychromatic white light of (mean +/-SEM) 6,036 +/-326 lux
      (approximately 17,685 +/-955 W/m2) during night shifts; dim light exposure after
      each night shift; an 8-hr sleep/darkness episode beginning 2 hrs after the end of
      each night shift. MEASUREMENTS: Melatonin and cortisol in plasma; clock genes
      HPER1, HPER2 and HBMAL1 RNA in PBMCs. RESULTS: Following 9 days on the night
      schedule, hormonal rhythms were adapted to the shifted schedule. HPER1 and HPER2
      expression in PBMCs displayed significant circadian rhythmicity, which was in a
      conventional relationship with the shifted sleep/wake schedule. Changes in the
      pattern of clock gene expression were apparent as of 3 days on the shifted
      sleep/wake schedule. CONCLUSIONS: This preliminary study is the first
      documentation of the effects of a shifted sleep/wake schedule on the circadian
      expression of both peripheral circadian oscillators in PBMCs and centrally-driven
      hormonal rhythms. In light of evidence associating clock gene expression with
      tissue function, the study of peripheral circadian oscillators has important
      implications for understanding medical disorders affecting night shift workers.

PMID- 18041478
TI  - Plasma melatonin rhythms in young and older humans during sleep, sleep
      deprivation, and wake.
AB  - STUDY OBJECTIVES: To determine the effects of sleep and sleep deprivation on
      plasma melatonin concentrations in humans and whether these effects are age
      dependent. DESIGN: At least 2 weeks of regular at-home, sleep/wake schedule
      followed by 3 baseline days in the laboratory and at least one constant routine
      (sleep deprivation). SETTING: General Clinical Research Center (GCRC), Brigham
      and Women's Hospital, Boston, MA. PARTICIPANTS: In Study 1, one group (<10 lux
      when awake) of 19 young men (18-30 y) plus a second group (<2 lux when awake) of
      15 young men (20-28 y) and 10 young women (19-27 y); in Study 2, 90 young men (18
      30 y), 18 older women (65-81 y), and 11 older men (64-75 y). All participants
      were in good health, as determined by medical and psychological screening.
      INTERVENTIONS: One to three constant routines with interspersed inversion of the
      sleep/wake cycle in those with multiple constant routines. MEASUREMENTS AND
      RESULTS: Examination of plasma melatonin concentrations and core body
      temperature. Study 1. There was a small, but significant effect of sleep
      deprivation of up to 50 hours on melatonin concentrations (increase of 9.81 +/-
      3.73%, P <0.05, compared to normally timed melatonin). There was also an effect
      of circadian phase angle with the prior sleep episode, such that if melatonin
      onset occurred <8 hours after wake time, the amplitude was significantly lower
      (22.4% +/- 4.79%, P <0.001). Study 2. In comparing melatonin concentrations
      during sleep to the same hours during constant wakefulness, in young men,
      melatonin amplitude was 6.7% +/- 2.1% higher(P <0.001) during the sleep episode.
      In older men, melatonin amplitude was 37.0% +/- 12.5% lower (P <0.05) during the
      sleep episode and in older women, melatonin amplitude was non-significantly 10.9%
      +/- 8.38% lower (P = 0.13) during the sleep episode. CONCLUSIONS: Both sleep and
      sleep deprivation likely influence melatonin amplitude, and the effect of sleep
      on melatonin appears to be age dependent.

PMID- 18041479
TI  - Practice parameters for the clinical evaluation and treatment of circadian rhythm
      sleep disorders. An American Academy of Sleep Medicine report.
AB  - The expanding science of circadian rhythm biology and a growing literature in
      human clinical research on circadian rhythm sleep disorders (CRSDs) prompted the
      American Academy of Sleep Medicine (AASM) to convene a task force of experts to
      write a review of this important topic. Due to the extensive nature of the
      disorders covered, the review was written in two sections. The first review
      paper, in addition to providing a general introduction to circadian biology,
      addresses "exogenous" circadian rhythm sleep disorders, including shift work
      disorder (SWD) and jet lag disorder (JLD). The second review paper addresses the
      "endogenous" circadian rhythm sleep disorders, including advanced sleep phase
      disorder (ASPD), delayed sleep phase disorder (DSPD), irregular sleep-wake rhythm
      (ISWR), and the non-24-hour sleep-wake syndrome (nonentrained type) or free
      running disorder (FRD). These practice parameters were developed by the Standards
      of Practice Committee and reviewed and approved by the Board of Directors of the
      AASM to present recommendations for the assessment and treatment of CRSDs based
      on the two accompanying comprehensive reviews. The main diagnostic tools
      considered include sleep logs, actigraphy, the Morningness-Eveningness
      Questionnaire (MEQ), circadian phase markers, and polysomnography. Use of a sleep
      log or diary is indicated in the assessment of patients with a suspected
      circadian rhythm sleep disorder (Guideline). Actigraphy is indicated to assist in
      evaluation of patients suspected of circadian rhythm disorders (strength of
      recommendation varies from "Option" to "Guideline," depending on the suspected
      CRSD). Polysomnography is not routinely indicated for the diagnosis of CRSDs, but
      may be indicated to rule out another primary sleep disorder (Standard). There is
      insufficient evidence to justify the use of MEQ for the routine clinical
      evaluation of CRSDs (Option). Circadian phase markers are useful to determine
      circadian phase and confirm the diagnosis of FRD in sighted and unsighted
      patients but there is insufficient evidence to recommend their routine use in the
      diagnosis of SWD, JLD, ASPD, DSPD, or ISWR (Option). Additionally, actigraphy is
      useful as an outcome measure in evaluating the response to treatment for CRSDs
      (Guideline). A range of therapeutic interventions were considered including
      planned sleep schedules, timed light exposure, timed melatonin doses, hypnotics,
      stimulants, and alerting agents. Planned or prescribed sleep schedules are
      indicated in SWD (Standard) and in JLD, DSPD, ASPD, ISWR (excluding elderly
      demented/nursing home residents), and FRD (Option). Specifically dosed and timed
      light exposure is indicated for each of the circadian disorders with variable
      success (Option). Timed melatonin administration is indicated for JLD (Standard);
      SWD, DSPD, and FRD in unsighted persons (Guideline); and for ASPD, FRD in sighted
      individuals, and for ISWR in children with moderate to severe psychomotor
      retardation (Option). Hypnotic medications may be indicated to promote or improve
      daytime sleep among night shift workers (Guideline) and to treat jet lag-induced
      insomnia (Option). Stimulants may be indicated to improve alertness in JLD and
      SWD (Option) but may have risks that must be weighed prior to use. Modafinil may
      be indicated to improve alertness during the night shift for patients with SWD
      (Guideline).

PMID- 18041482
TI  - Sonographic measurement of lateral parapharyngeal wall thickness in patients with
      obstructive sleep apnea.
AB  - INTRODUCTION: Lateral parapharyngeal wall (LPW) thickness may be a predominant
      anatomic factor causing airway narrowing in apneic subjects. In this study, we
      explored sonographic measurement of the LPW thickness and compared the results
      with LPW thickness measured by magnetic resonance imaging (MRI). We also
      investigated the association between sonographic measurement of LPW thickness and
      apnea-hypopnea index (AHI). METHOD: Seventy-six patients with suspected
      obstructive sleep apnea (OSA) underwent ultrasound examination of LPW thickness
      after overnight polysomnography. Fifteen out of 76 subjects also participated in
      correlation and reliability studies of sonographic and MRI measurements of LPW
      thickness. RESULTS: There was good correlation between measurements of LPW
      thickness on ultrasound and MRI (r = 0.78, P = 0.001), although Bland-Altman
      analysis indicated overestimation of LPW thickness by ultrasound, when compared
      with the LPW as measured by MRI. The sonographic measurement of LPW thickness had
      high reproducibility, with intraclass correlation coefficients of 0.90 and 0.97
      for intraoperator and interoperator reliability, respectively. Fifty-eight
      subjects with significant OSA (AHI > or = 10/h) had a higher body mass index,
      larger neck circumference, and greater LPW thickness measured by ultrasound than
      those (n = 18) with an AHI of less than 10 per hour. LPW thickness had a positive
      correlation with AHI on univariate analysis (r = 0.37, P = 0.001). On
      multivariate analysis, LPW thickness had a positive independent association with
      AHI after adjustment for age, sex, neck circumference, and body mass index. The
      positive association of LPW thickness with AHI remained significant in both
      univariate and multivariate analyses of men only (n = 62). CONCLUSIONS:
      Sonographic measurement of LPW thickness is a novel and reliable technique and
      had good correlations with measurement by MRI and the severity of OSA. Ultrasound
      may provide an alternative imaging modality with easy accessibility and lower
      cost in OSA research.

PMID- 18041483
TI  - Sleep apnea in heart failure increases heart rate variability and sympathetic
      dominance.
AB  - AIMS: Sleep disordered breathing (SDB) is common in heart failure and ventilation
      is known to influence heart rate. Our aims were to assess the influence of SDB on
      heart rate variability (HRV) and to determine whether central sleep apnea (CSA)
      and obstructive sleep apnea (OSA) produced different patterns of HRV. METHODS AND
      RESULTS: Overnight polysomnography was performed in 21 patients with heart
      failure and SDB. Two 10-minute segments each of SDB and stable breathing from
      each patient were visually identified and ECG signal exported for HRV analysis.
      SDB increased total power (TP) with very low frequency (VLF) power accounting for
      the greatest increase (1.89+/-0.54 vs 2.96+/-0.46 ms2, P <0.001); LF/HF ratio
      increased during SDB (1.2+/-1.0 vs 2.7+/-2.1, P <0.001). Compared to OSA, CSA was
      associated with lower absolute LF (2.10+/-0.47 vs 2.52+/-0.55 ms2, P = 0.049) and
      HF power (1.69+/-0.41 vs 2.34+/-0.58 ms2, P = 0.004), increased VLF% (78.9%+/
      13.4% vs 60.9%+/-19.2%, P = 0.008), decreased HF% (6.9%+/-7.8% vs 16.0%+/-11.7%,
      P = 0.046) with a trend to higher LF/HF ratio. CONCLUSIONS: SDB increases HRV in
      the setting of increased sympathetic dominance. HRV in CSA and OSA have unique
      HRV patterns which are likely to reflect the different pathophysiological
      mechanisms involved.

PMID- 18041481
TI  - Circadian rhythm sleep disorders: part II, advanced sleep phase disorder, delayed
      sleep phase disorder, free-running disorder, and irregular sleep-wake rhythm. An
      American Academy of Sleep Medicine review.
AB  - OBJECTIVE: This the second of two articles reviewing the scientific literature on
      the evaluation and treatment of circadian rhythm sleep disorders (CRSDs),
      employing the methodology of evidence-based medicine. We herein report on the
      accumulated evidence regarding the evaluation and treatment of Advamced Sleep
      Phase Disorder (ASPD), Delayed Sleep Phase Disorder (DSPD), Free-Running Disorder
      (FRD) and Irregular Sleep-Wake Rhythm ISWR). METHODS: A set of specific questions
      relevant to clinical practice were formulated, a systematic literature search was
      performed, and relevant articles were abstracted and graded. RESULTS: A
      substantial body of literature has accumulated that provides a rational basis the
      evaluation and treatment of CRSDs. Physiological assessment has involved
      determination of circadian phase using core body temperature and the timing of
      melatonin secretion. Behavioral assessment has involved sleep logs, actigraphy
      and the Morningness-Eveningness Questionnaire (MEQ). Treatment interventions fall
      into three broad categories: 1) prescribed sleep scheduling, 2) circadian phase
      shifting ("resetting the clock"), and 3) symptomatic treatment using hypnotic and
      stimulant medications. CONCLUSION: Circadian rhythm science has also pointed the
      way to rational interventions for CRSDs and these treatments have been introduced
      into the practice of sleep medicine with varying degrees of success. More
      translational research is needed using subjects who meet current diagnostic
      criteria.

PMID- 18041480
TI  - Circadian rhythm sleep disorders: part I, basic principles, shift work and jet
      lag disorders. An American Academy of Sleep Medicine review.
AB  - OBJECTIVE: This the first of two articles reviewing the scientific literature on
      the evaluation and treatment of circadian rhythm sleep disorders (CRSDs),
      employing the methodology of evidence-based medicine. In this first part of this
      paper, the general principles of circadian biology that underlie clinical
      evaluation and treatment are reviewed. We then report on the accumulated evidence
      regarding the evaluation and treatment of shift work disorder (SWD) and jet lag
      disorder (JLD). METHODS: A set of specific questions relevant to clinical
      practice were formulated, a systematic literature search was performed, and
      relevant articles were abstracted and graded. RESULTS: A substantial body of
      literature has accumulated that provides a rational basis the evaluation and
      treatment of SWD and JLD. Physiological assessment has involved determination of
      circadian phase using core body temperature and the timing of melatonin
      secretion. Behavioral assessment has involved sleep logs, actigraphy and the
      Morningness-Eveningness Questionnaire (MEQ). Treatment interventions fall into
      three broad categories: 1) prescribed sleep scheduling, 2) circadian phase
      shifting ("resetting the clock"), and 3) symptomatic treatment using hypnotic and
      stimulant medications. CONCLUSION: Circadian rhythm science has also pointed the
      way to rational interventions for the SWD and JLD, and these treatments have been
      introduced into the practice of sleep medicine with varying degrees of success.
      More translational research is needed using subjects who meet current diagnostic
      criteria.

PMID- 18041484
TI  - Reduced cerebral blood flow during wakefulness in obstructive sleep apnea
      hypopnea syndrome.
AB  - STUDY OBJECTIVES: To investigate changes in regional cerebral blood flow (rCBF)
      in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). DESIGN: We
      compared the 99mTc-ethylcysteinate dimer (ECD) single photon emission computed
      tomography (SPECT) images of patients with OSAHS with those of age- and sex
      matched healthy volunteers. SETTING: University hospital. PATIENTS AND
      PARTICIPANTS: Twenty-seven patients with severe OSAHS and 27 healthy volunteers
      underwent 99mTc-ECD brain SPECT studies. INTERVENTION: For statistical parametric
      mapping analysis, all SPECT images were spatially normalized to the standard
      SPECT template and then smoothed using a 14-mm full-width at half-maximum
      Gaussian kernel. The Student t test was used for the statistical analysis.
      MEASUREMENTS AND RESULTS: The mean age of patients and subjects was 44.3 years
      (range 31-58). All patients underwent overnight polysomnography. The mean apnea
      hypopnea index of patients was 60.4 +/- 17.6 per hour (range 33 -104), indicating
      severe OSAHS. All patients snored heavily and had daytime sleepiness (mean
      Epworth Sleepiness Scale score, 10.7 +/- 3.7, range 6-12). Statistical parametric
      mapping analysis showed that rCBF in patients with OSAHS was significantly
      reduced in bilateral parahippocampal gyri and in the right lingual gyrus, as
      compared with that of healthy volunteers (P < 0.05 with false discovery rate
      correction). Moreover, apnea-hypopnea indexes of patients were negatively
      correlated with rCBF in the right pericentral gyrus and right cuneus at
      uncorrected P < 0.001. CONCLUSIONS: Our results show the altered rCBF pattern in
      bilateral parahippocampal gyri, right lingual gyrus, pericentral gyrus, and
      cuneus in patients with severe OSAHS. These findings may partly explain the
      deficit in memory, spatial learning, executive function, and attention, which are
      frequently found in patients with OSAHS.

PMID- 18041485
TI  - Zaleplon and zolpidem objectively alleviate sleep disturbances in mountaineers at
      a 3,613 meter altitude.
AB  - STUDY OBJECTIVES: To assess the effects of zolpidem and zaleplon on nocturnal
      sleep and breathing patterns at altitude, as well as on daytime attention,
      fatigue, and sleepiness. DESIGN: Double-blind, randomized, placebo-controlled,
      cross-over trial. SETTING: 3 day and night alpine expedition at 3,613 m altitude.
      PARTICIPANTS: 12 healthy male trekkers. PROCEDURE: One week spent at 1,000 m
      altitude (baseline control), followed by 3 periods of 3 consecutive treatment
      nights (N1-3) at altitude, to test 10 mg zolpidem, 10 mg zaleplon, and placebo
      given at 21:45. MEASURES: Sleep from EEG, actigraphy and sleep logs; overnight
      arterial saturation in oxygen (SpO2) from infrared oximetry; daytime attention,
      fatigue and sleepiness from a Digit Symbol Substitution Test, questionnaires, and
      sleep logs; acute mountain sickness (AMS) from the Lake Louise questionnaire.
      RESULTS: Compared to baseline control, sleep at altitude was significantly
      impaired in placebo subjects as shown by an increase in the amount of Wakefulness
      After Sleep Onset (WASO) from 17 +/- 8 to 36 +/- 13 min (P<0.05) and in arousals
      from 5 +/- 3 to 20 +/- 8 (P<0.01). Slow wave sleep (SWS) and stage 4 respectively
      decreased from 26.7% +/- 5.8% to 20.6% +/- 5.8% of total sleep time (TST) and
      from 18.2% +/- 5.2% to 12.4% +/- 3.1% TST (P<0.05 and P<0.001, respectively).
      Subjects also complained from a feeling of poor sleep quality combined with
      numerous 02 desaturation episodes. Subjective fatigue and AMS score were
      increased. Compared to placebo control, WASO decreased by approximately 6 min
      (P<0.05) and the sleep efficiency index increased by 2% (P<0.01) under zaleplon
      and zolpidem, while SWS and stage 4 respectively increased to 22.5% +/- 5.4% TST
      (P<0.05) and to 15.0% +/- 3.4% TST (P<0.0001) with zolpidem only; both drugs
      further improved sleep quality. No adverse effect on nighttime SpO2, daytime
      attention level, alertness, or mood was observed under either hypnotic. AMS was
      also found to be reduced under both medications. CONCLUSIONS: Both zolpidem and
      zaleplon have positive effects on sleep at altitude without adversely affecting
      respiration, attention, alertness, or mood. Hence, they may be safely used by
      climbers.

PMID- 18041486
TI  - Liability to anxiety and severe life events as predictors of new-onset sleep
      disturbances.
AB  - STUDY OBJECTIVES: This study examined the effects of liability to anxiety and
      stressful life events on the onset of sleep disturbances. DESIGN: A 5-year
      longitudinal observational cohort study. PARTICIPANTS: A population sample of
      16,627 men and women with undisturbed sleep and 2572 with disturbed sleep at
      baseline. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Liability to anxiety, as
      indicated by a general feeling of stressfulness (the Reeder stress inventory) and
      symptoms of sympathetic nervous system (SNS) hyperactivity, was assessed at
      baseline. The occurrence of post-baseline life events and sleep disturbances was
      measured at follow-up five years later. Both liability to anxiety and exposure to
      negative life events were strongly associated with sleep disturbances. Among the
      men liable to anxiety, the odds of sleep disturbances were 3.11 (95% CI 1.90
      5.10) times higher for those who had experienced a severe life event within 6
      months than for the others. For the men not liable to anxiety, the corresponding
      odds ratio was only 1.13 (95% CI 0.40-3.18). For the men and women liable to
      anxiety, the odds ratio for sleep disturbance 0-6 months after divorce was 2.05
      (95% CI 1.38-3.05), with the corresponding odds ratio being 1.47 (95% CI 0.84
      2.58) for the men and women not liable to anxiety. The effects of total or
      specific life events on sleep after 6 months were not dependent on liability to
      anxiety. CONCLUSION: This study provides prospective evidence that individuals
      liable to anxiety may be at particularly high risk of post-event sleep
      disturbances at least during the first months after the event.

PMID- 18041487
TI  - Dysfunctional beliefs and attitudes about sleep (DBAS): validation of a brief
      version (DBAS-16).
AB  - STUDY OBJECTIVE: Sleep related cognitions (e.g., faulty beliefs and appraisals,
      unrealistic expectations, perceptual and attention bias) play an important role
      in perpetuating insomnia. This paper presents new psychometric data on an
      abbreviated version of the Dysfunctional Beliefs and Attitudes about Sleep Scale
      (DBAS-16), a 16-item self-report measure designed to evaluate a subset of those
      sleep related cognitions. DESIGN: Psychometric study of a patient-reported
      measure of sleep related beliefs based on existing clinical and research
      databases. PARTICIPANTS: A total of 283 individuals (60% women; mean age of 46.6
      years old) with insomnia, including 124 clinical patients and 159 research
      participants. MEASUREMENTS AND RESULTS: Participants completed the DBAS, Insomnia
      Severity Index, Beck Depression and Anxiety Inventories, daily sleep diaries for
      2 weeks, and 3 nights of polysomnography (research sample only) as part of a
      baseline assessment. The DBAS-16 was found to be reliable, as evidenced by
      adequate internal consistency (Cronbach alpha = 0.77 for clinical and 0.79 for
      research samples) and temporal stability (r = 0.83). The factor structure was
      similar to the original 30-item version, with 4 factors emerging and reflecting:
      (a) perceived consequences of insomnia, (b) worry/helplessness about insomnia,
      (c) sleep expectations, and (d) medication. DBAS total scores were significantly
      correlated with other self-report measures of insomnia severity, anxiety, and
      depression, but not with specific sleep parameters. CONCLUSION: The psychometric
      qualities of this abbreviated DBAS-16 version seem adequate. This patient
      reported measure should prove a useful instrument to evaluate the role of sleep
      related beliefs and attitudes in insomnia and to monitor change on this cognitive
      variable as a potential moderator of treatment outcome.

PMID- 18041488
TI  - Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary
      insomnia.
AB  - STUDY OBJECTIVES: To evaluate the efficacy and safety of doxepin 1, 3, and 6 mg
      in insomnia patients. DESIGN: Adults (18-64 y) with chronic primary insomnia (DSM
      IV) were randomly assigned to one of four sequences of 1 mg, 3 mg, and 6 mg of
      doxepin, and placebo in a crossover study. Treatment periods consisted of 2
      polysomnographic assessment nights with a 5-day or 12-day drug-free interval
      between periods. Efficacy was assessed using polysomnography (PSG) and patient
      reported measures. Safety analyses included measures of residual sedation and
      adverse events. MEASUREMENTS AND RESULTS: Sixty-seven patients were randomized.
      Wake time during sleep, the a priori defined primary endpoint, was statistically
      significantly improved at the doxepin 3 mg and 6 mg doses versus placebo. All
      three doses had statistically significant improvements versus placebo for PSG
      defined wake after sleep onset, total sleep time, and overall sleep efficiency
      (SE). SE in the final third-of-the-night also demonstrated statistically
      significant improvement at all doses. The doxepin 6 mg dose significantly reduced
      subjective latency to sleep onset. All three doxepin doses had a safety profile
      comparable to placebo. There were no statistically significant differences in
      next-day residual sedation, and sleep architecture was generally clinically
      preserved. CONCLUSIONS: In adults with primary insomnia, doxepin 1 mg, 3 mg, and
      6 mg was well-tolerated and produced improvement in objective and subjective
      sleep maintenance and duration endpoints that persisted into the final hour of
      the night. The side-effect profile was comparable to placebo, with no reported
      anticholinergic effects, no memory impairment, and no significant hangover/next
      day residual effects. These data demonstrate that doxepin 1 mg, 3 mg, and 6 mg is
      efficacious in improving the sleep of patients with chronic primary insomnia.

PMID- 18041489
TI  - Evaluation of automated and semi-automated scoring of polysomnographic recordings
      from a clinical trial using zolpidem in the treatment of insomnia.
AB  - OBJECTIVE: To evaluate the performance of 2 automated systems, Morpheus and
      Somnolyzer24X7, with various levels of human review/editing, in scoring
      polysomnographic (PSG) recordings from a clinical trial using zolpidem in a model
      of transient insomnia. METHODS: 164 all-night PSG recordings from 82 subjects
      collected during 2 nights of sleep, one under placebo and one under zolpidem (10
      mg) treatment were used. For each recording, 6 different methods were used to
      provide sleep stage scores based on Rechtschaffen & Kales criteria: 1) full
      manual scoring, 2) automated scoring by Morpheus 3) automated scoring by
      Somnolyzer24X7, 4) automated scoring by Morpheus with full manual review, 5)
      automated scoring by Morpheus with partial manual review, 6) automated scoring by
      Somnolyzer24X7 with partial manual review. Ten traditional clinical efficacy
      measures of sleep initiation, maintenance, and architecture were calculated.
      RESULTS: Pair-wise epoch-by-epoch agreements between fully automated and manual
      scores were in the range of intersite manual scoring agreements reported in the
      literature (70%-72%). Pair-wise epoch-by-epoch agreements between automated
      scores manually reviewed were higher (73%-76%). The direction and statistical
      significance of treatment effect sizes using traditional efficacy endpoints were
      essentially the same whichever method was used. As the degree of manual review
      increased, the magnitude of the effect size approached those estimated with fully
      manual scoring. CONCLUSION: Automated or semi-automated sleep PSG scoring offers
      valuable alternatives to costly, time consuming, and intrasite and intersite
      variable manual scoring, especially in large multicenter clinical trials.
      Reduction in scoring variability may also reduce the sample size of a clinical
      trial.

PMID- 18041490
TI  - Sleep architecture and NREM alterations in children and adolescents with Asperger
      syndrome.
AB  - STUDY OBJECTIVES: To analyze sleep in children with Asperger syndrome (AS) by
      means of standard sleep questionnaires, to evaluate sleep architecture and NREM
      sleep alterations by means of cyclic alternating pattern (CAP) and to correlate
      objective sleep parameters with cognitive behavioral measures. DESIGN: Cross
      sectional study involving validated sleep questionnaires, neuropsychological
      scales, and PSG recording. SETTING: Sleep medicine center. PARTICIPANTS: Eight
      children with AS, 10 children with autism, and 12 healthy control children.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Children with AS had a higher
      prevalence of problems of initiating sleep and daytime sleepiness. Sleep
      architecture parameters showed minor differences between the 3 groups. CAP
      parameters showed an increased percentage of A1 and a decreased percentage of A2
      subtypes in subjects with AS vs. controls. All A subtype indexes (number per hour
      of NREM sleep) were decreased, mostly in sleep stage 2 but not in SWS. With
      respect to children with autism, subjects with AS showed increased CAP rate in
      SWS and A1 percentage. In subjects with AS, verbal IQ had a significant positive
      correlation with total CAP rate and CAP rate in SWS and with global and SWS A1
      index. The percentage of A2 negatively correlated with full scale IQ, verbal and
      performance IQ. CBCL total score correlated positively with CAP rate and A1 index
      while externalizing score correlated negatively with A3%. CONCLUSIONS: This study
      shows peculiar CAP modifications in children with AS and represents an attempt to
      correlate the quantification of sleep EEG oscillations with the degree of mental
      ability/disability.

PMID- 18041492
TI  - Costly infections. A new CMS hospital-acquired infection mandate is putting
      hospitals on the alert.

PMID- 18041491
TI  - Automatic analysis of single-channel sleep EEG: validation in healthy
      individuals.
AB  - STUDY OBJECTIVE: To assess the performance of automatic sleep scoring software
      (ASEEGA) based on a single EEG channel comparatively with manual scoring (2
      experts) of conventional full polysomnograms. DESIGN: Polysomnograms from 15
      healthy individuals were scored by 2 independent experts using conventional R&K
      rules. The results were compared to those of ASEEGA scoring on an epoch-by-epoch
      basis. SETTING: Sleep laboratory in the physiology department of a teaching
      hospital. PARTICIPANTS: Fifteen healthy volunteers. MEASUREMENTS AND RESULTS: The
      epoch-by-epoch comparison was based on classifying into 2 states (wake/sleep), 3
      states (wake/REM/ NREM), 4 states (wake/REM/stages 1-2/SWS), or 5 states
      (wake/REM/ stage 1/stage 2/SWS). The obtained overall agreements, as quantified
      by the kappa coefficient, were 0.82, 0.81, 0.75, and 0.72, respectively.
      Furthermore, obtained agreements between ASEEGA and the expert consensual scoring
      were 96.0%, 92.1%, 84.9%, and 82.9%, respectively. Finally, when classifying into
      5 states, the sensitivity and positive predictive value of ASEEGA regarding
      wakefulness were 82.5% and 89.7%, respectively. Similarly, sensitivity and
      positive predictive value regarding REM state were 83.0% and 89.1%. CONCLUSIONS:
      Our results establish the face validity and convergent validity of ASEEGA for
      single-channel sleep analysis in healthy individuals. ASEEGA appears as a good
      candidate for diagnostic aid and automatic ambulant scoring.

PMID- 18041493
TI  - All hype? Have business intelligence tools actually changed, or have they just
      been repackaged and renamed?

PMID- 18041494
TI  - Taking out the trash. Figuring out the best way to get rid of PCs fraught with
      mercury, lead and private patient information is far from simple.

PMID- 18041495
TI  - Tracking with RFID. Brigham and Women's is keeping tabs on expensive equipment
      and valuable devices with the help of an indoor positioning system.

PMID- 18041496
TI  - AHIC 2.0. The next generation of the American Health Information Community is
      almost here, yet there are still many more questions than answers.

PMID- 18041497
TI  - PACS grows up. As imaging technology matures into its second generation, the
      industry begins to feel the shift forward.

PMID- 18041498
TI  - Climb every mountain. Getting the right PACS may feel like climbing a mountain,
      exhausting and never-ending at the same time.

PMID- 18041499
TI  - The vendor selection. For hospitals that perform tens of thousands of procedures
      a year, choosing a vendor can be a tricky operation.

PMID- 18041500
TI  - Bringing health home. Though some say the verdict is still out on telehealth
      because of funding questions, many proponents say its value is unquestionable.

PMID- 18041501
TI  - Looking for adventure. Anticipated regulatory changes may alter the entire
      landscape for ambulatory surgery center joint ventures.

PMID- 18041502
TI  - To outsource or not to outsource. When looking to offload non-core functions,
      healthcare CFOs shouldn't just focus on dollars and cents.

PMID- 18041503
TI  - Accelerating adoption. When it comes to getting everyone on board with RIS and
      PACS, sometimes a new model is all that's needed.

PMID- 18041504
TI  - Chasing the carrot. There is money to be gained through P4P incentives but
      getting it is no easy task.

PMID- 18041505
TI  - Floundering in fluoride fog.

PMID- 18041506
TI  - The art and science of pediatric dentistry.

PMID- 18041507
TI  - Evidence-based assessment of tooth-colored restorations in proximal lesions of
      primary molars.
AB  - The purpose of this study was, using evidence-based dentistry, to compare the
      successes of glass ionomer cement (GIC), resin-modified GIC (RmGIC), composite
      resin (CR), and polyacid-modified composite resin (PAMCR) in primary molar
      proximal lesions. METHODS: The PICOT question was: P: in primary molar proximal
      lesions; I: does the use of 1 material (GIC, RmGIC, CR, or PAMCR); C: compared
      with the remaining materials; O (Outcome): result in higher success rates; T:
      when followed for at least 1 year? Relevant articles (256) were identified from
      databases then sieved by titles, abstracts, and full texts. Following exclusions,
      36 dinical trials-including 25 randomized clinical trials (RCTs)-remained.
      Extracted data were meta-analyzed. RESULTS: GIC restorations had a significantly
      (P<.05) lower likelihood of success than RmGIC and CR restorations. Overall
      success rates were: (1) GIC (691 restorations)=75%; (2) RmGIC (276)=89%; (3) CR
      (620)=83%; (4) PAMCR (596)=87%. Mean success rates did not differ significantly
      (P>.05): (1) GIC (6 studies)=65+/-34%; (2) RmGIC (3 studies)=93+/-7%; (3) CR (7
      studies)=85+/-12%; and (4) PAMCR (8 studies)=90+/-10%. CONCLUSIONS: Few articles
      were available to determine the best material. Recognizing material improvements
      since 1990, earlier data may be noncomparable. RmGIC had the highest success
      rates, but fewest studies and fewest restorations; only one product was
      assessable. Prospective RCTs should be of at least 5 years' duration to determine
      correctly the success rate of Class II restorations in primary molars.

PMID- 18041508
TI  - Effect of motivational interviewing on rates of early childhood caries: a
      randomized trial.
AB  - PURPOSE: The purposes of this randomized controlled trial were to: (1) test
      motivational interviewing (MI) to prevent early childhood caries; and (2) use
      Poisson regression for data analysis. METHODS: A total of 240 South Asian
      children 6 to 18 months old were enrolled and randomly assigned to either the MI
      or control condition. Children had a dental exam, and their mothers completed
      pretested instruments at baseline and 1 and 2 years postintervention. Other
      covariates that might explain outcomes over and above treatment differences were
      modeled using Poisson regression. Hazard ratios were produced. RESULTS: Analyses
      included all participants whenever possible. Poisson regression supported a
      protective effect of MI (hazard ratio [HR]=0.54 (95%CI=035-0.84)-that is, the M/
      group had about a 46% lower rate of dmfs at 2 years than did control children.
      Similar treatment effect estimates were obtained from models that included, as
      alternative outcomes, ds, dms, and dmfs, including "white spot lesions."
      Exploratory analyses revealed that rates of dmfs were higher in children whose
      mothers had: (1) prechewed their food; (2) been raised in a rural environment;
      and (3) a higher family income (P<.05). CONCLUSIONS: A motivational interviewing
      style intervention shows promise to promote preventive behaviors in mothers of
      young children at high risk for caries.

PMID- 18041509
TI  - Caries risk-based fluoride supplementation for children.
AB  - PURPOSE: The purpose of this study was to evaluate primary care physicians'
      recommendation of fluoride supplements based upon a child's caries risk. METHODS:
      A representative sample of family physicians (FPs) and pediatricians (PDs) in the
      United States was mailed a letter and a questionnaire that described case
      scenarios of 2-year-old children-one with low and the other with high caries-risk
      -as well as questions about opinions on fluoride supplement use. The physicians'
      opinions were compared with CDC experts' consensus on the same scenarios.
      RESULTS: The response rates were 43% for FPs and 52% for PDs. FPs and PDs had a
      high agreement level (76% ond 80%, respectively) with CDC experts regarding the
      need for fluoride supplementation of the high-risk child. For o low risk child,
      all physicians showed a significantly lower level of agreement with the CDC
      experts (15% for FPs; 7% for PDs). CONCLUSIONS: The majority of primary care
      physicians follow the current fluoride supplementation guideline without
      considering the caries risk status of a child. If caries risk status is to be
      used to tailor preventive regimens, then physicians need to be educated on how to
      identify children with the highest need for prevention.

PMID- 18041510
TI  - Common dental conditions associated with dental erosion in schoolchildren in
      Australia.
AB  - PURPOSE: The purpose of the investigation was to determine factors associated
      with dental erosion in a group of schoolchildren in Queensland, Australia.
      METHODS: Dental examinations were carried out on 714 children aged 5.5 to 14.6
      years from 8 randomly selected Australian schools. A total of 3,165 primary and
      2,976 permanent teeth were scored for dental erosion using a modified erosion
      index. Dental caries experience was determined from clinical examination and
      bitewing radiographs. Enamel defects were recorded using the developmental
      defects of enamel index. RESULTS: There were 225 children (32%) who exhibited no
      erosion and 489 (68%) who had erosion of at least one tooth. Erosion was found in
      78% of subjects with primary teeth and 25% of subjects with permanent teeth
      (P<.001). Children with erosion in the primary and permanent dentition were more
      likely to have: (1) a lower socioeconomic status (primary dentition, P<.001 and
      permanent dentition (P<.001); (2) enamel hypoplasia in permanent dentition
      (P=.001); (3) dental caries in the primary dentition (P=.001); and (4) permanent
      dentition (P=.002). CONCLUSIONS: In Australian schoolchildren, the prevalence of
      dental erosion in the primary dentition is approximately 3 times greater than in
      the permanent dentition. Dental erosion is strongly associated with caries
      experience and enamel hypoplasia.

PMID- 18041511
TI  - Texas dentists' attitudes toward the Dental Medicaid program.
AB  - PURPOSE: The purpose of this study was to report the attitudes of Texas dentists
      toward the Dental Medicaid program. METHODS: A self-administered survey was
      mailed to all pediatric dentists and a random sample of general dentists.
      RESULTS: Surveys from 347 (69%) of 500 dentists (171 of 295 general dentists
      [58%] and 169 of 205 pediatric dentists [82%]) were returned. 57% of pediatric
      dentists and 29% of general dentists (P<.0001) treated at least 1 Medicaid
      patient in the past year. The major areas of dissatisfaction were: (1) broken
      appointments; (2) low reimbursement levels; and (3) patient noncompliance. This
      mirrors results from studies in Iowa, Louisiana, Ohio, Washington, and
      California. Both pediatric and general practitioners identified the following
      barriers to core for the Medicaid population: (1) low dental IQ; (2) few
      providers; and (3) no transportation. CONCLUSIONS: The major areas of
      dissatisfaction included both programmatic and patient-related factors.
      Attributes of the system (eg, lower reimbursement levels) are more modifiable
      than attributes of the patient population (eg, patient noncompliance and low
      dental IQ). Underfunding of dental Medicaid is endemic to all states studied in
      the literature. Providers, legislators, and government programs should target the
      programmatic problems with future efforts and funding.

PMID- 18041512
TI  - Pulp revascularization of a necrotic infected immature permanent tooth: case
      report and review of the literature.
AB  - The purpose of this report was to present the case of a patient wherein
      revascularization of the necrotic infected pulp space of an immature permanent
      maxillary central incisor tooth was induced in vivo by stimulation of a blood
      clot from the periapical tissues into the canal space. This was achieved after
      disinfection of the canal space with a topical antibiotic paste followed by a
      blood clot scaffold induced from the periapical tissues. This treatment approach
      offers clinicians great potential to avoid the need for traditional apexification
      with calcium hydroxide or the need to achieve an artificial apical barrier with
      mineral trioxide aggregate. Furthermore, this treatment approach can help rescue
      infected immature teeth by physiologically strengthening the root walls.

PMID- 18041513
TI  - Dental management of a talon cusp on a primary incisor.
AB  - There are many treatment options for the pediatric patient with a talon cusp
      (TC). The purpose of this paper was to report the case of a TC involving a
      primary maxillary right central incisor in a 14-month-old male causing
      displacement of the affected tooth. The etiology of a TC is thought to be a
      disturbance during the morphodifferentiation stage of tooth development. Clinical
      problems include: (1) occlusal interferences; (2) esthetic disturbances; (3)
      accidental cusp fracture; (4) tongue irritation; (5) nursing difficulty; (6)
      caries; and (7) displacement of the affected tooth. The TC affecting the central
      incisor was reduced over a period of 4 visits, followed by immediate placement of
      a 5% sodium fluoride varnish at the conclusion of each reduction visit.
      Restoration of esthetics and function was evident within 1 month following
      complete cusp reduction. There were no clinical signs of any problems related to
      the reduction, and the prognosis was considered to be guarded. The pediatric
      patient was placed on a 6-month oral hygiene maintenance follow-up.

PMID- 18041514
TI  - Management of avulsed permanent incisors: a comprehensive update.
AB  - An avulsion injury is a challenge to manage, and there are many factors to
      consider to obtain the best prognosis in each scenario. In 2001, Lee and
      colleagues published decision analysis paradigms for the management of avulsed
      permanent teeth for the purpose of providing busy clinicians with user-friendly,
      reference-based flow-charts to facilitate the best possible outcomes for managing
      these teeth in children and adolescents. The purpose of this article was to
      update the 2001 flow-charts and decision analyses with: (1) current concepts; (2)
      recent literature-based findings; and (3) new philosophies.

PMID- 18041515
TI  - Ethics and leadership in children's oral health.
AB  - PURPOSE: This paper reviews key ethical precepts in health care for children, and
      explores how interpretations of justice predict different and sometimes
      conflicting approaches to children's dental needs. Ethics is a core competency
      for health professionals because of their special responsibilities toward
      patients and the public. Ethical principles guiding health professionals include:
      (1) beneficence; (2) nonmaleficence; (3) respect for autonomy; and (4) justice.
      Different theories of justice lead to different responses toward public needs,
      such as access to dental care. The most frequently encountered response in the
      dental community is volunteerism, consistent with the libertarian perspective on
      justice. Though desirable, volunteerism alone will never solve dental access
      issues because such efforts do not address the problems systematically. A policy
      statement of the American Academy of Pediatric Dentistry (AAPD) explicitly
      recognizes that children have a right to oral health care. Children's unique
      characteristics--their vulnerability, dependence, and developmental processes
      call for special arrangements to address their health needs. Given the importance
      of children to society, it is critical that all health sectors work together to
      address children's health and well-being. However, those with the greatest
      knowledge of children's oral health needs-pediatric dentists-must take a
      leadership role in creating and supporting solutions to these needs. The AAPD has
      an opportunity to support systemic solutions at the state and national level to
      ensure that all children have access to oral health care. One example of a
      systemic solution is the Access to Baby and Child Dentistry (ABCD) program in
      Washington State.

PMID- 18041516
TI  - [Intrafamiliar violence against pregnant adolescents].
AB  - The objective of this work is to describe how the adolescents had relationship
      with their relatives before and after the discovery of the pregnancy. Fifteen
      adolescents from a public maternity that were in the post-partum period
      participated fo the research. A semi-strcutred interview was used as instrument
      of data collection. Qualitative approach was used for data analysis. Results
      indicated that the adolescents had a good relationship, but when the pregnancy
      was revealed they became victims of violent acts by their parents and that
      dialogue about sexuality and contraception is still distant between parents and
      children.

PMID- 18041517
TI  - [Characterization of suicide cases in a Brazilian northeastern capital].
AB  - A descriptive, retrospective study which aimed to characterize suicide in the
      municipality of Teresina, Piaui, the period of 2000-2005, in regards to the
      social demographic aspects, means of death and period (month) of the act. The
      results were obtained through the Institute of Legal Medicine, they show a
      greater rate of suicide among men (71.3%) with a greater frequency of the youth
      population, predominance among the single (54.9%). The occupational groups with
      the greatest percentage were students (23.8%). The most frequently used method
      was hanging (66%) followed by firearms (13.1%). The use of interventions in hopes
      of lowering the current rates is imperative, as suicide occupies fourth place in
      relation to all causes of violent deaths in the municipality.

PMID- 18041518
TI  - [Correlation between the carotid resistance and functional autonomy of old
      women].
AB  - This study had as objective to correlate the resistance of the carotid artery and
      the functional autonomy of old women. The resistance of the carotid artery was
      evaluated through the method called Doppler and the functional autonomy through
      tests related to daily activities (Protocol GDLAM). In the description of the
      data it was used measures of localization and dispersion. The internal right
      carotid resistance got mean and pattern deviation respectively (0.71 +/- 0.07)
      and functional autonomy mean and pattern deviation respectively (30.40 +/- 6.31).
      The coefficient of the correlation of Spearman showed a strong association
      between the variation of the study (r = 0.998; p = 0.000). The results suggest
      that the bigger the table of contents of the resistance of the carotid artery is
      the bigger will be the difficulty of execution of the daily life tasks.

PMID- 18041519
TI  - [Feelings and expectations of the women concerning oncotic citology].
AB  - Qualitative study whose objective was to argue and to describe the feelings and
      the expectations lived deeply for 28 women about oncotic citology in a unit of
      the Family Health Program in Parnaiba-PI, through an interview with script of
      opened questions. The results were presented in categories and evidenced that the
      majority of the women do not carry through the examination, even so they all
      affirm the importance of this, mainly for detention of illnesses. It was observed
      despite during the procedure, the feelings most recurrent between the women were:
      shyness, unreliability, fear, shame and pain. Related to the expectations, they
      wish a better attendance of the professionals, and a result that does not present
      alterations, in special the cancer.

PMID- 18041520
TI  - [Mental health in the family health program].
AB  - A descriptive study whose objective was to identify the education and actions of
      the nurse in Mental Health (MH), in the Family Health Program. The sample
      consisted of 134 acting nurses at the Family Health Program in Teresina, Piaui
      The results show that 95.5% don't have the specified education in MH. Of those
      interviewed, 97% state that there are patients, in their assigned areas, that
      need this type of care. The referenced actions were home visits (60%)
      appointments (27.7%), referrals (21.5%), medication delivery (15.4%), inactivity
      (14.6%), ambulatory service (7.7%), community therapy (5.4%) and casework (0.8%).
      Methods and strategies of public policies related to this area should be
      revisited and instituted in order to (re)direct ways of reform in the actions and
      services of mental health.

PMID- 18041521
TI  - [Vertical transmission of HIV: situation found in a maternity of Teresina].
AB  - The increase of the number of cases of AIDS among women reveals a progressive
      increase of the vertical transmission of HIV in Brazil, as well as in Piaui
      Considering the relevance of the subject, this study had as objective to analyze
      the conditions of the implementation of the rules and measures recommended by the
      Ministry of Health to prevent the vertical transmission of HIV in maternity
      houses of Teresina-PI. The theoretical-methodological approach included the study
      of organizational dynamics and its actors, by means of qualitative approach. In
      order to obtain data, 17 semi-structured interviews were carried out. The results
      revealed that the recommendations of the Ministry of Health were totally
      followed, making more evident the weakness of the assistance provided, to the
      mother/son binomial.

PMID- 18041522
TI  - [The pedagogical practice of nursing teachers and their knowledge].
AB  - This article has as objectives investigate the faculty knowledge that embase the
      pedagogical practice of the nursing-professors, glimpsing to understand the
      meaning of this social practice in what it refers to the process to become a
      professional professor. The qualitative nature study, with methodological
      emphasis in verbal story, used as instruments of data collection semi-arranged
      interviews, and the data analysis starting from the content analysis. Among the
      results obtained from the analysis, it has proven that the faculty knowledge and
      the pedagogical practice positively incises for the consolidation of the process
      to become professional professor in the scope of the faculty in the nursing
      course at UFPI.

PMID- 18041523
TI  - [Socio-political aspects of the implantation of the Transplant Center of Piaui].
AB  - A qualitative study aiming at understanding the socio-political aspects that
      mediate the implantation of the Transplant Center of Piaui, identify the social
      topics involved in this implantation and analyze the participation of the
      organized civil society. Ten people directly related to the implantation of the
      transplant center were involved in the study, selected through the "snowball"
      technique. A loosely structured interview, taped, transcribed and submitted for
      thematic analysis was used. It was concluded that the implantation of the
      transplant center in Piaui was the fruit of a complex series of negotiations and
      interests among the State and organized civil society, as there was no political
      project for action in the area of transplants. This distancing from the
      responsibility of the public sector characterizes the importance that was given
      to this implantation.

PMID- 18041524
TI  - [Change in the collective construction in the nursing undergraduate nursing
      course: a challenge].
AB  - This study aims to draw up a proposal of integration for the fourth term of
      Nursing from NOVAFAPI. The main focus was to describe the subjects' structure
      chain, the competencies and abilities to be developed, as well as discuss the
      methodology and the method of assessment specified and draw up a proposal for the
      fourth term. A qualitative approach was used, based on the action research
      referential. The subjects were the faculties and students from the term, plus the
      coordinator of the course. Its results show there is already the understanding
      that the integrated curriculum will contribute for the education of subjects more
      capable of transforming social reality.

PMID- 18041525
TI  - [Nosocomial infection: study of prevalence at a public teaching hospital].
AB  - This study aimed to determine the prevalence of nosocomial infection (NI) and
      distribution for topography and microorganism and its antimicrobial sensibility.
      The study was carried out in two Intensive Care Units (ICUs) of a public teaching
      hospital of Teresina, with sampling of 394 NI cases and processed by the SPSS
      Software. The respiratory infection was the biggest prevalence (61.26%) in the
      General ICU. It was found a bigger bacterial sensibility to amicacine (52.48%) in
      the ICU of the ER. The microorganism with bigger prevalence was Klebsiella
      pneumonia (35.46%) in the general ICU. In conclusion, the prevalence of NI in the
      two ICUs was 60.8%, exceeding 45.3% of the general rate registered in the
      Brazilian hospitals that is 15.5%, contributing to increase the morbi-mortality
      caused by infections.

PMID- 18041526
TI  - [Gender differences in the elderly].
AB  - Qualitative study that aimed at investigating present and decisive gender
      subjects of health and elder people's life quality. The subjects were 20 (twenty)
      seniors of the Programa Terceira Idade em Acao-PTIA. The semi-structured
      interview was used as data collection technique. From the speeches, information
      that answered the investigation inquietudes emerged and they made possible the
      formulation of three analysis categories. In the first, it stood out the low self
      esteem lived by the men when they age, otherwise in the second one it was
      evidenced the autonomy and the freedom conquered by the senior women, and in the
      third category the learning happened among the old ladies who participated of
      PTIA. Concluding that there is influence of the gender subjects in health and
      life quality in aging.

PMID- 18041527
TI  - [Social representations of the legal implications of nosocomial infection and its
      control].
AB  - The study aimed at learning the social representations of the legal implications
      of hospital infections (HI) and analyze how these representations are articulated
      with the quality of work developed by the health and law professionals. The data
      were produced through interviews and processed by software Alceste4.8. The
      descendant hierarchical analysis showed 04 classes of words, that objected the
      legal implications of HI, anchored in the ideological, historical and socio
      cultural aspects, in the rights that the health user has not run risks, resulting
      of occurences caused by negligence of involved in the process having to be
      fiscalized by the competent organs in order the responsibles answer civily and
      penaltily, miscase or miscare in hospital assistance.

PMID- 18041528
TI  - [Knowledge, contraceptive practice and HIV/AIDS prevention among university
      students].
AB  - Descriptive research of qualitative approach, with the study object about college
      medicine and nursing students concerning the contraceptive choice and DST/SIDA
      control. Identifying the contraceptive method choice between these graduating,
      and to evidence if they associate the methods to the prevention of the DST's/SIDA
      or not. The data were collected by semi-structured interviews in ribbon cassette.
      The produced data were reorganized and analyzed based on theoretical referencial.
      Results alert for changes in students attitudes needs either in current education
      way, to offer support so that they really understand the importance and necessity
      of safe sexual practical, and associates contraceptive methods to sexual
      diseases, HIV/AIDS control beyond planned pregnancy prevention.

PMID- 18041529
TI  - [Vaccine influenza: knowledge, attitudes and practices of elderly in Teresina].
AB  - This objective study to raise the knowledge, practical and attitudes of the aged
      ones of an area of the Program of Health of Familia (PSF) on the vaccine it
      counts influenza and to identify the reasons that had taken some not to be
      vaccinated. It consists of a domiciliary inquiry, an area of the PSF of Teresina,
      with 74 aged ones from 60 years. The result had evidenced that even so 85.3% have
      inadequate knowledge on the vaccine, 89.1% is favorable. The reasons most
      frequent for the vaccination had not been illness and fear of the adverse events.
      It is concluded that the favorable attitude regarding the vaccination can modify
      the practical front it, restoring behavior of self-protection and greater
      adhesion.

PMID- 18041530
TI  - [Analysis of after-vacination side-effects occurred in Teresina].
AB  - This study focuses the profile of the adverse events after-vaccine occurrences in
      Teresina in 2006. The data had been collected by means of the form application
      with 73 participants in 18 Basic Units of Health. The results show that the
      vaccines that had more produced events adverse had been tetravalente, BCG and DPT
      The events most frequent had been: fever, hiporresponsivo hipotonic episode,
      moderate irritability and local manifestations. Amongst the behaviors adopted for
      the health professionals, 80% had been approximately adjusted. The year minors
      had been accomitted by the events. All the events had evolved for the cure. It
      was concluded that the action of vaccination still continues requiring constant
      qualification of the professionals of the area. It is suggested to deepen the
      knowledge with relation to the handling, diagnosis, inquiry and treatment.

PMID- 18041531
TI  - [Analysis of the scientific production about the aged in REBEn].
AB  - This is a bibliographic research that aimed at analyzing the scientific
      production about the aged in Revista Brasileira de Enfermagem (Brazilian Nursing
      Journal), in the period from 2000 to 2006. It was carried out bibliographic data
      bases using the following descriptors: senior, nursing, gerontology. It was
      analyzed eighteen scientific articles. In 2004 it happened the largest number of
      publications. Regarding authorship of the articles, most had the participation of
      doctors, most of this production concentrated on the southeast area with
      qualitative approach and preponderance of hospital as the scenario. The
      scientific production of nursing about the aged is initial, recent and relevant.

PMID- 18041532
TI  - [Humanization and nursing assistance to normal childbirth].
AB  - Bibliographical study that sought to identify the scientific production about
      humanization and nursing assistance to normal childbirth. The sources were
      scientific articles from SCIELO-Brasil's database, from 2000 to 2007. We obtained
      13 articles as result from the search, which were grouped in the following
      categories: childbirth medicalization, humanization of assistance to childbirth,
      companion during childbirth and performance of the obstetric nurse. The analysis
      pointed out that the current paradigm is centralized on childbirth intervention,
      despite of humanization movements defending the natural and physiological
      childbirth made by the nurse. We concluded that qualified and humanized
      assistance to childbirth and birth privileges women's respect, dignity and
      autonomy, regarding women's active role in the birth process.

PMID- 18041533
TI  - [Nurse-teacher: a dialogue with pedagogical education].
AB  - College faculty presents itself as an important subject matter in a moment of
      transformation on nursing education characterized by syllabus and methodological
      changes. This assignment aimed to reflect upon the pedagogical education of the
      nurse-teacher in order to make this education appropriate to assist the new
      educational demands of society which are considered by the Syllabus Guidelines of
      Nursing Graduation. It is about a bibliographical study. The literature review
      permits to state that pedagogical education is necessary for the nurse-teacher to
      educate a nurse capable of acting in all care dimensions as a promoter for the
      health of the citizen, the family and the community. In this context, the
      reflecting practice is pointed out as guideline to the development of faculty
      education.

PMID- 18041534
TI  - [Teaching and learning with multiple sclerosis patients: experience report].
AB  - This report describes the experience of a group of nursing students from
      Universidad Federal do Piaui, in face of the reality of multiple sclerosis
      patient. The experience highlight the necessity of an integrated team to achieve
      fundamental knowledge and to offer a holistic assistance to the patient. The
      impact of the actions developed by the students, in APPEM (Piauiense Association
      of Multiple Sclerosis), allows them to better coexist with the difficulties of
      the disease. In addition, the general community is favored through the knowledge
      transmited by the activities developed by the group. We conclude that a wider
      knowledge about a full of mysteries pathology is only possible when the theory is
      combined with the reality of the patient.

PMID- 18041535
TI  - [Collective memory of the Brazilian Nursing Association--Piaui Section].
AB  - Historical and social study that aimed at obtaining the social representations
      about associative practice present at the collective memory of the members from
      ABEn-PI. Its primary source were 94 minutes of ABEn-PI created from 1959 to 1970
      and from 1995 to 2005 and analyzed according to a thematic analysis of
      categorical content. The social representations obtained were about knowledge,
      positioning and feelings about nursing teaching, religiosity and honoring and
      political fights of ABEn. The dissemination of these knowledge, positioning and
      feelings among the members of the association, showed the spread of social
      representations determining the behavior of these nurses as ABEn-PI members.

PMID- 18041536
TI  - [From population to individual approach in the primary prevention of vascular
      disease: let's not miss the trees for the forest].

PMID- 18041537
TI  - [Ethical and practical problems of secondary prevention. Two paediatrics
      examples].
AB  - The concept of prevention is surrounded by a halo of optimism that can sometimes
      confuse, since it is not always borne out by the facts. The saying, "An ounce of
      prevention is worth a pound of cure", is not always true. Moreover, preventive
      activities should be based on a much more solid scientific basis than curative
      activities, since we offer the former as an option, whereas we are required to
      provide the latter. This article reviews two examples of paediatric screening
      instruments-one for neuroblastoma, and the other for hip dysplasia-which provide
      an opportunity to evaluate the practical problems of secondary prevention. These
      two instruments are used to examine a few general but important issues in
      screening, such as the need to know the natural history of the disease, and the
      "point of no return" (the moment past which early diagnosis and early
      intervention are no longer so effective in improving the course of the disease).
      In conclusion, only sometimes "an ounce of cure is worth a pound of prevention",
      and regardless of the value of a given screening instrument, clinicians should
      use the same level of scientific rigor to judge preventive activities as they use
      for curative activities.

PMID- 18041538
TI  - [Predictive capacity, comparison and clinic consequences of the Framingham-Wilson
      and REGICOR tables in persons for whom care has been provided at a health care
      center, Badajoz, Spain].
AB  - BACKGROUND: Framingham's original equation modified by Wilson and the REGICOR
      calibration are widely recommended in coronary risk stratification. This study is
      aimed at: (1) Analyzing the ten-year predictiveness of the Framingham-Wilson and
      REGICOR tables among a population for which care has been provided at an urban
      health care center (2) Evaluating the concordance use of hypolipemiant and
      antihypertensive drugs resulting from these tables. METHODS: Observational,
      longitudinal, retrospective study of a cohort of patients for whom care was
      provided at a primary care center. A total of 1011 patients ages 35-74 (mean age
      55.7, 56.0% females) without any evidence of cardiovascular disease. Those
      patients having a > or =20% risk in Wilson and > or =10% in REGICOR were
      considered high-risk. RESULTS: The actual coronary risk of the population was
      10.7%, whilst the mean coronary risk estimated with the functions was 17.0% in
      Wilson and 6.6% in REGICOR. A total 29.6% was classified high-risk in Wilson as
      compared to the 18.2% in RECIGOR (p < 0.05). The percentage of high-risk males
      was significantly higher in Wilson than in REGICOR (49.0% vs. 29.4%, p < 0.01).
      The Kappa index was 0.70 (95 CI: 0.67, 0.73). A total of 39.5% of the patients
      (as per Wilson) and 31.4% (as per REGICOR) were candidates for taking
      hypolipemiant drugs (p < 0.001). The validity criteria of both of these functions
      are quite discreet: sensitivity, specificity and odds ratio diagnosed at 50.9%,
      73.1% and 2.11 in Wilson and 28.7%, 83.1% and 1.98 in REGICOR, respectively.
      CONCLUSIONS: The Wilson and REGICOR tables show an acceptable degree of
      concordance, but their validity parameters are discreet. The Framingham-Wilson
      function screens a higher percentage of patients as being candidates for
      hypolipemiant drugs.

PMID- 18041539
TI  - [Cardiovascular risk of hypertensive people with long-range monitoring. The
      effect of aging (Ciclo Risk Study)].
AB  - BACKGROUND: The evolution of estimated cardiovascular risk can be for evaluating
      the effectiveness of the different treatment interventions which are carried out
      on patients with regular follow-up by family physicians. This study is aimed at
      evaluating the effect of aging on the evolution of cardiovascular risk among
      hypertensive patients with long-range Primary Care monitoring. METHODS:
      Longitudinal, descriptive study with monitoring of 842 hypertensive patients
      within the 34-70 age range at two primary care centers, with a quality
      improvement intervention (improvement cycle) during the last year at one of these
      centers. The main variables were age and gender, blood pressure, lipids, smoking
      habit, diabetes and cardiovascular risk (CVR) (Framingham-Wilson) in the real
      life situation and considering the age constant in the first case, and the risk
      factors in the second, plus the relative risk. RESULTS: A drop was found in the
      systolic and diastolic blood pressure from 11.78 mmHg (95 IC: 10.51-13.05) and
      8.83 mmHg (95 CI: 8.13-9.53), respectively, and LDL Cholesterol 15.94 mg/dl (95
      CI: 11.77-20.12), a rise in HDL-Cholesterol of 7.53 mg/dl (95C1: 6.39-8.66),
      decreased smoking habit of 31% and an increase in diabetics. The Coronary risk
      decreased 1.40 percent points, Coronary risk with age constant decreased 3.84 (95
      CI: 3.35-4.33), having increased with constant risk factors by 3.06(95 CI: 2.82
      3.29). The Relative risk dropped from 2.50 to 1.85. CONCLUSIONS: Aging may mask
      the effect achieved by health care in the absolute cardiovascular risk check. The
      relative risk could be an alternative for monitoring the follow-up.

PMID- 18041540
TI  - [Trends in effects of maximum temperatures on organic-cause mortality in Castile
      La Mancha, Spain from 1975 to 2003].
AB  - BACKGROUND: Non-lineal temperature-mortality relationship varies depending on the
      characteristics of the designated study geographic zone. In given places, a
      growing level of economic development has led to lesser influence of
      environmental variables on mortality. This paper analyzes trends in the
      association between maximum temperatures and organic-cause mortality from 1975 to
      2003 in Castile-La Mancha (Spain). METHODS: Daily maximum temperatures and
      organic-cause mortality data were divided into 3 time period: 1975-1984, 1985
      1994 and 1995-2003. After data pre-whitening by applying ARIMA model estimated
      for the daily maximum temperature series, we calculate cross-correlation
      functions between residuals of temperature and mortality, 7 days lagged for
      summer, 15 for cold months, and comparing its correlation coefficients. RESULTS:
      We observe an increasing number of significant lags during the warm season (p <
      0.05) between first and second decades studied in regional overall but with some
      provincial differences. In the third study period the number of significant lags
      varies slightly, although cross correlation coefficients were significantly
      upward (p < 0.05) at lag 3 in the entire region and Toledo in particular.
      CONCLUSIONS: Maximum temperature and mortality by organic cause association
      became more extensive and intense since 1975-1984 decade in Castile-La Mancha.
      The aging of regional population could offset the probable beneficial effect of
      economic growth on this relationship. No appreciable time trends are found in
      cold months.

PMID- 18041541
TI  - [Evaluation of the surveillance system for human immunodeficiency virus
      infections of Navarra, Spain, 1985-2003].
AB  - BACKGROUND: Navarra has an information system of HIV diagnoses working since the
      beginning of the epidemic up to the present day. This study aims at describing
      and evaluating this system, focusing on its sensitivity. METHODS: The updated
      guidelines for evaluating public health surveillance systems from the CDC were
      used to describe the purpose and operation of the system and to analyse its
      attributes for the period 1985-2003. For the evaluation of the sensitivity the
      regional database of antiretrovirals distribution was used. RESULTS: The HIV
      surveillance system of Navarra is confidential and name-based, and includes all
      HIV-infection cases diagnosed each year. The information sources of the system
      are: (a) all the laboratories in the public health system that perform the
      western blot test, and (b) hospital discharge registries. The system covers the
      entire population of Navarre (584,734 inhabitants). It uses the HIV case
      definition proposed by the European Centre for the Epidemiological Monitoring of
      AIDS. The system is well-accepted by the community and by all the stakeholders,
      including those providing data. By the end of 2003 it included 2302 HIV cases,
      and 98.8% of all patients who had ever received antiretrovirals in Navarra.
      CONCLUSIONS: The HIV information system of Navarra is simple, useful, well
      accepted and highly sensitive. The information about antiretroviral distribution
      was useful for this evaluation.

PMID- 18041542
TI  - [Recommendations for health research and information on definitions and variables
      for the study of the foreign-born immigrant population].
AB  - BACKGROUND: The growth of the foreign population residing in Spain makes it
      necessary to avail of better information on the level of health. In the health
      information and research systems, no uniform criteria currently exist for the
      nomenclature of origin-related variables. This study poses a consensus on the
      definitions of immigrant and foreigner. METHODS: Employing the Delphi
      methodology, 66 experts in immigration from different disciplines were invited to
      take part in the study using a two-round questionnaire with suggested
      definitions, terms and variables, including in the second round the percentages
      of responses and the comments made by the participants in the first. The
      suggestions regarding which an 80% consensus was reached were put into a final
      document which was approved in the third round. RESULTS: A total of 57 people
      accepted the invitation, 44 having completed at least one round and 33 having
      completed all three. Some of the most important aspects regarding which a
      consensus was reached were: the term "immigrant" denotes the individual who comes
      to a country where he/she was not born to take up residency, one not being an
      immigrant on a lifelong basis. Those individuals born in another country who have
      arrived in Spain less than 5-10 years ago can be considered immigrants; and
      immigrated people are all those individuals born in another country.
      Socioeconomic variables, gender, administrative status and country of origin
      should also be taken into consideration. The children of immigrated individuals
      who are born in Spain must not be considered individuals who are born in Spain
      must not be considered. CONCLUSIONS: To properly define the inmigrating and
      immigrated population categories, the health studies and information systems must
      include country of birth, year of arrival and nationality.

PMID- 18041543
TI  - [Hospital admissions for infectious diseases: 1999-2003 incidence in one health
      district in the autonomous community of Valencia, Spain].
AB  - BACKGROUND: . Infectious diseases are still currently one of the leading causes
      of death and illness. Their dynamic nature justifies the epidemiological study
      thereof. This study is aimed at analyzing the incidence of infectious diseases
      most often conditioning hospital admissions. METHODS: A study was conducted of
      those individuals admitted to hospital during the 1999-2003 period whose main
      diagnosis at admission to hospital had been encoded according to the
      International Disease Classification (ICD 9-CM) as an infectious disease in the
      Minimum Basic Data Set. A total of 2010 active infectious disease codes were
      selected and were grouped into 25 groups as per the ICD 9-CM. The target
      population was that of one district in the Autonomous Community of Valencia.
      RESULTS: A total of 9.7% of the admissions during the period under study (8,585
      records) were due to an infectious disease. Those affected averaged 38 years of
      age, median age of 37, standard deviation 31 and the range of 1-102 years. The
      admissions of males (54.5%) prevailed over females (48.5%). The incidence rate of
      admissions due to infectious diseases was 728 cases / 100,000 inhabitants / year.
      The highest rate of admissions was among young children and the elderly. The
      groups of diseases showing the largest number of admissions were, in descending
      order, infectious digestive, respiratory and genitourinary diseases. CONCLUSION:
      The hospital admissions due to infections diseases totaled one tenth of the
      admissions, and 7/1000 inhabitants/year required hospitalization for an
      infectious disorder. The highest incidence rates were found for intestinal
      diseases, digestive, respiratory and genitourinary tract diseases among the
      childhood-aged population, but also, although in smaller percentages, among
      individuals over 65 years of age.

PMID- 18041544
TI  - [Use of geographic restrictions in PubMed].

PMID- 18041545
TI  - [Worker's life before and after repetive cumulative trauma (RCT) and
      osteomuscular work-related disease (OWRD)].
AB  - This is a qualitative work, which focused on workers routine before and after
      being affected by RCT/ OWRD. The study aimed at verifying and analyzing if
      workers' lives had changed after the disease diagnostic. The research took place
      at sections of the TRT-AL--a Court responsible for labor conciliations in Maceio 
      Alagoas. The information was collected based on semi-structured interviews and
      data were analyzed based on the following tematics: life before RCT/OWRD; the
      activity that caused it; the diagnosis; an answer to the repetitive work and a
      new perspective to the horizon. Results enabled researchers to suggest preventive
      care, as well as to contribute for reducing damages caused by repetitive
      activities and high pressure on workers.

PMID- 18041546
TI  - [The facets of "touching", "staying" and "dating": social representations of
      relationships among adolescents].
AB  - This study aimed at describing and analyzing the different forms of interpersonal
      relationships among adolescents. Social representations approach was adopted as
      the theoretical-methodological reference. Subjects were 130 adolescent and data
      collection was accomplished with focal groups, in 19 encounters, from March to
      June 2004. A analysis was accomplished with software Alceste. Results revealed
      the distribution of the contents in six categories and the different forms of
      relationships were identified in class 1, by recognizing three types: "touching",
      "staying" and "dating". It is concluded that adolescents experiment a tension
      between the attractions exercised by freedom (touching/staying) and by
      affectivity (dating). It was also highlighted the social fluidity both
      adolescence, so that those, modifying the intensity/modality of relationships
      along short periods of time.

PMID- 18041547
TI  - [Why the nursing staff professionals with urinary incontinence do not seek for
      treatment].
AB  - It was verified the prevalence of urinary incontinence (UI) among the women's
      nurse staff at a medical school, if the incontinent women seek a doctor for
      treatment and what was they reasons for not seeking treatment. Among 291 women
      that answer the survey, 27.5% reported UI and, 79% women didn't seek UI
      treatment. The most common reasons for not seek treatment were that incontinence
      was slight degree (28.8%) and the belief that the UI was a common problem for
      women (22%). The prevalence and the reasons for not seeking treatment for UI were
      similar the others researches with women in general. It was concluded that the
      factor at to be health's professional didn't influence their attitudes.

PMID- 18041548
TI  - [Curricular Guidelines for Nursing Graduate Course: contexts, changes and
      perspectives].
AB  - Research focusing the curricular guidelines for Nursing Faculty in Brazil as
      approved in 2001 by the Resolution no 03/2001-CNE. The study aimed at
      contextualizing and rescueing the historical elaboration process of these
      guidelines, to discuss the approved content supporting elements to guide the
      construction of politician-pedagogical projects. Bibliographical sources,
      documents and interviews were used. Pedagogical principles present in the
      guidelines were verified; the discussion on the research were approached; the
      nursery licentiature degree, the Unique System of Health as focus of the
      formation and the performance of the United Net. The context of the private
      higher education and health, the economic changes (financial globalization, the
      performance of international agencies) had conformed the scenery of changes in
      the graduation in Brazil in the 90' and beginning of the 21st century.

PMID- 18041549
TI  - [Caregiver role strain in caregivers of children with cancer].
AB  - The purpose of this study was to identify the frequency of nursing diagnoses
      "caregiver role strain" and "risk for caregiver role strain" in 50 caregivers of
      children with cancer in a specialized children's cancer hospital in Campinas, Sao
      Paulo. The data for this descriptive cross-sectional study was obtained from the
      patients' files and interviews held with the caregiver using a specially
      formulated protocol. "Caregiver role strain" was presented by 78% of the
      caregivers and 100% presented the risk for "caregiver role strain" with at least
      two defining characteristics and six risk factors. The conclusion was that
      caregivers of children with cancer present a high risk for caregiver role strain.

PMID- 18041550
TI  - [HIV positive pregnant women who do not follow the prenatal prophylaxis].
AB  - This is an exploratory study based on a qualitative approach. The objective was
      to investigate why HIV positive pregnant women do not follow the treatment which
      is recommended by the Health Ministry during the prenatal period. The individuals
      participating of this investigation were seven HIV positive women who, during
      their pregnancy, did not follow the prophylaxis treatment currently recommended.
      The data were collected by means of semi-structured interviews. Categories based
      on what these individuals reported were then stipulated and the results showed
      that women are in a vulnerable position regarding the negotiation of safe sex
      with their partners. Moreover, low social and economical conditions and lack of
      affection lead women to become victims of HIV/AIDS.

PMID- 18041551
TI  - [Family violence in the perspective of the child who goes to day care center and
      pre-school].
AB  - The present research uses the descriptive and traversal study and also the
      content analysis to know the family violence in children of day care center and
      pre-schools. The population and the subjects are constituted of infantile
      educators, teachers and monitors. It is verified in the results the presence of
      the domestic violence, practiced mainly by the mother, the aggressive child is
      present in the atmosphere of the schools as a form of reproduction of behavior
      and also, the negligence regarding the cares and the attention to the child in
      the daily. These behaviors can generate other violence forms, maintaining the
      child always in risk atmospheres during several phases of the life.

PMID- 18041552
TI  - [Family caregiver activity: meanings and beliefs].
AB  - This qualitative study aims at apprehending the meanings and beliefs of caregiver
      of people with methabolic syndrome in the domiciliar context. It used the
      symbolic interactionism as theoretical referential, following the content
      analysis approach of Bardin. For data collection the semi-structured interviews
      and the free observation were used, in the period from march to may, 2005. The
      results demonstrate important work overload delivered to the relative by the
      caregiver, which implies in meaningful impact about physical, emotional and
      social health. It was concluded that reflections about the person who is
      continously involved with their relatives' care must be intensified, aiming at a
      better preparation of them to domiciliar therapeutic accompanying.

PMID- 18041553
TI  - [Work accidents involving nursing workers].
AB  - The objective of this study was to identify and analyze work accidents as well
      the activities in which the nursing workers are exposed to. This is a study case,
      descriptive and exploratory, developed in a University Hospital in the Brazilian
      Federal District. It was done a survey on work accidents registered in SESMT and
      CCIH, from January 1998 to December 2002 and is was also identified work
      activities related to these accidents. We could noticed that the workers suffered
      76 accidents. From those accidents 83.95% happened due to sharpened materials;
      8.64% due to falls; 6.17% due to exposition to biological fluids and 1.24% due to
      injuries. The diversity and simultaneity of the work activities contribute to the
      occurrence of the work accidents.

PMID- 18041554
TI  - [Red reflex: prevention way to blindness in childhood].
AB  - This study had as objective to investigate the result and the colour gradation of
      red reflex test in newborns (NB). It is a exploratory, quantitative study and the
      sample was 180 NB from maternity ward in Fortaleza-CE. From this, 156 showed
      result "no altered" and 24 "suspect". About the aspect of red reflex, 144 NB
      showed the same coloration in the two eyes, in 35 of this, the colour was red, in
      33, orange reddish, in 46 orange colour, in 24 light yellow, in 6 yellow with
      whitish stains central. Of the suspect cases, the reflex was light yellow with
      whitish stains with lines. The nurse trained to accomplish the red reflex test
      can have important role at Neonatal Unit with actions about the prevention of
      ocular alterations in the childhood.

PMID- 18041555
TI  - [Humanization in nursing care: acting with respect in a school hospital].
AB  - The purpose of the present study was to verify the hospital routine aspects in
      which nurses see bioethic principles when giving attendance and verify in which
      situations the nurse understands that the respect concept is connected to their
      routine. An exploratory, decriptive and qualitative approach research was
      performed with 18. The categories found were: The interference of bioethic
      principles in the nursing practice; How to respect the patient despite the
      hospital routines; How to render care to the patient in a humanized way and How
      to put into practice the humanization theory. We concluded that nurses understand
      that the bioethic principles help them in their daily nursing routine because
      they can orient themselves in their actions, making respect to the patient happen
      very naturally. However, nurses also understand that the principles can have
      their link hindered by their own Hospital rules.

PMID- 18041556
TI  - [A proposal for a geometrical delimitation model for ventro-gluteal injection].
AB  - This study aimed at presenting and comparing geometrical and traditional
      technique for intramuscular injection in the ventrogluteal area. This is a quasi
      experimental study of non-equivalent control group type, carried out with
      anatomical parts of corpses to verify the precision of function between
      traditional delimitation using hand as reference and the geometrical model which
      was constituted by tracing imaginary lines across bone structures of the hip,
      making a configuration of a triangle whose barycenter points the punction site.
      The study demonstrated that the punction site delimited by the geometrical
      technique keeped proportion of the envolved structures, and matched with the
      muscular womb of the ventrogluteal area in 100% of punctions. In another hand, in
      the traditional technique the punction site varied in 39.9% of punctions.

PMID- 18041557
TI  - [The meaning of family for homosexual couples].
AB  - This study aimed at understanding the structure and the dynamics of the family of
      couples constituted by people of the same sex, approaching the basis of its
      experience. The phenomenological approach was used with interviews. From analysis
      of the testimonies added to our experiences and readings resulted in two thematic
      categories: "the meaning of the family, constituted by homosexuals" and
      "perceiving the impact and the value of the family". Based on the phenomenon
      understanding, new perspectives are glimpsed, therefore, when somebody you decide
      to compose a different family of that proposal for the traditional model, he/she
      also will be creating a new condition, or either, a new type of family. In
      nursing care it is necessary to be aware for new care needs in order that the
      different types of family can be attended with the same ethics and respect and
      also considering the privacy guarantee.

PMID- 18041558
TI  - [Modulators of sleeping habits in childhood].
AB  - This literature review presents the main organic, psychological and cultural
      factors influencing the sleeping habits of infants. By means of a clinical
      anthropological approach, the interrelation between these habits and
      biobehavioral and psychosocial stressing factors is described, as well as
      cultural practices such as shared bed, night feeding, transitional objects and
      use of dummies. It presents some measures that may modulate the physiology of
      sleep and home practices of sleeping in childhood.

PMID- 18041559
TI  - [The teaching of biosafety in undergraduate nursing: a literature review].
AB  - It's a study that made a scientific production survey in nursing regarding to
      biosafety teaching aiming to investigate its context and discover the content of
      publishing on biosafety teaching in the nursing undergraduation. It was analyzed
      the journal articles found consulting LILACS, SciELO, MEDLINE, BDENF, DEDALUS and
      PERIENF databases, identifying 26 articles. The results found provided the
      creation and discussion of these categories: "Ideological and theoretical bases",
      "Historic approach of biosafety", "Occupational risks and AIDS" and "Biosafety
      education in graduation". It was concluded that the number of articles is small,
      mainly the ones focusing on biosafety teaching, but there was an evolution of
      this content in the last years.

PMID- 18041560
TI  - [Analysis of a scientific article: an exercise].
AB  - This essay describes the analysis of a scientific article, with the purpose of
      demonstrating the operability of that activity, common for all the high level
      professionals, especially researchers. 23 items were selected as the most
      relevant ones in this type of analysis, and each item, besides describing some
      analysis criteria, also used a selected scientific article to exemplify the
      analysis. It concludes that the analysed scientific study was well prepared and
      with high quality.

PMID- 18041561
TI  - [Decision-making process and health management councils: theoretical approaches].
AB  - With the institutionalization of participation in health, through conferences and
      management councils at national, state, municipal and local levels, a process of
      democratization is initiated in the health area. However, in relation to the
      health councils in particular, there is still much to be done, including
      improving the quality of the decision-making process. This work aims to place the
      decision-making process in its theoretical context in terms of participatory
      democracy, elements which make up, factors which influence its development, and
      finally, to explore some possibilities of this theoretical basis to analyze the
      practices of the health councils in the area of health. It is hoped that it will
      make a theoretical contribution to the analyses carried out in this area, in
      order to provide a decision-making process that is more inclusive in terms of
      participation.

PMID- 18041562
TI  - [Distance education as strategy for permanent education in health: possibilities
      and challenges].
AB  - The point of this study is to reflect about how important Permanent Education in
      Health (PEH) is in the promotion of the changes process of professors of UEFS; to
      establish strategies to promote PEH and show the possibilities and challenges to
      the operate of DE as strategy to PEH. Bibliographical Revision Study: The result
      shows that PEH is one strategy to professional formation through colletive works
      between professors. As possibility: DE makes possible a new style in formation
      construction. Challenges: Knowledge need to use new technologies of information
      and communication; difficulty of access to these technologies; scarcity of time
      to develop the course activities. We learn that DE have a new perspective to PEH.

PMID- 18041563
TI  - [Living groups: contributions for an educational proposal for tuberculosis].
AB  - This study is a report on care practice. Its objective was to develop a proposal
      for education in health care from a group of people with tuberculosis, seeking to
      increase the effectiveness of their treatment. The data was obtained through a
      proposal for education in health care, developed through a living group. Two
      interrelated themes resulted from the process of analyzing the data: the
      perception of tuberculosis and its care and treatment, and social isolation.
      These represent the elements that influence education in health care for people
      with tuberculosis, as well as the meaning that such a situation has to these
      people.

PMID- 18041564
TI  - [Hypertrophic cardiomyopathy: update and nursing assistance].
AB  - This is an update that aimed to describe some aspects of physiopathology of
      Hypertrophic Cardiomyopathy (HCM) and its therapeutics correlating them to
      nursing assistance. Data source was based on LILACS bibliographical database
      using the search expression "hypertrophic cardiomiopathy" and "nursing care". The
      HCM is a disease that appears from cromossomic alterations that causes
      hypertrophy of the left ventricule and can cause heart failure, functional class
      III and IV. Treatment consists in using palliative medications or other
      procedures like Pace-Maker implantation, ventriculoplasty and heart
      transplantation. Nursing assistance based on Nursing Diagnoses and Intereventions
      are presented.

PMID- 18041565
TI  - [The safety of enoxaparine use in elderly with acute myocardial infarction].
AB  - BACKGROUND/AIM: Enoxaparin (ENOX), the low-molecular-weight heparin, used in
      acute myocardial infarction (AMI) could lead to hemorrhage. The aim of this study
      was to determine wether bleeding was more often in AMI patients older than 65 or
      75 years who receive ENOX or unfractionated heparin (UFH). METHODS: Among the
      patients with AMI hospitalized during three successive months receiving ENOX or
      UFH, three group of parameters were investigated: demographic, ischemic and
      bleeding TIMI criteria. RESULTS: Among 85 hospitalized patients with signs of
      AIM, there were 35 (41.2%) old 65 years or less, 32 (38.5) old 66-75 years and 18
      (21.2%) older than 75 years. In AMI elderly patients, according to the received
      ENOX/UFH: ischemic complication (18.2 vs. 21.4%) were insignificantly lower and
      the number of lethal outcomes (18.2 vs. 17.8%) were insignificantly more often in
      ENOX group; represented only by one patient (age beyond 75 years), major and non
      major bleeding events occurred only in UFH group. CONCLUSION: The ENOX usage in
      AMI in patients older than 65 years did not show any significant difference in
      efficacy and bleeding rate comparing to UFH.

PMID- 18041566
TI  - [Determination of diazepam and its metabolites in serum by the use of liquid
      chromatography-mass spectrometry method].
AB  - BACKGROUND/AIM: Diazepam is a benzodiazepine anxyolitic. Metabolism of diazepam
      takes place in liver which generates pharmacologically active metabolites N
      desmethyldiazepam, temazepam and oxazepam. The aim of this study was to develop
      and validate the method of liquid chromatographymass spectrometry (LC-MS) for
      separation and determination of diazepam and its active metabolites in the serum
      of rats samples after i.p. application of diazepam in a dose of 10 mg/kg.
      METHODS: The serum samples taken from Wistar rats, were used in LC-MS analysis
      after the application of 10 mg/kg of diazepam i.p. RESULTS: After alkaline
      extraction from the serum samples with diethylether and separation on a C18
      reversed-phase column by using mobile phase methanolglacial acetic acid-water
      (50:1:49 v/v), diazepam and its metabolites were quantified. Determination was
      performed in a selective ion monitoring (SIM) mode, thereby the other exogenous
      and endogenous compounds did not interfere with this assay. Diazepam, N
      desmethyldiazepam, oxazepam and temazepam were eluted in 14 minutes. The standard
      curve was linear in the range from 10-2 000 ng/ml. The limits of detection for
      diazepam, N-desmethyldiazepam, oxazepam and temazepam were 4.37, 3.13, 4.38 and
      7.31 ng/ml, respectively. The limits of quantitation for diazepam, N
      desmethyldiazepam, oxazepam and temazepam were 14.58, 10.41, 14.59 and 24.36
      ng/ml, respectively. CONCLUSION: The described LC-MS is a simple, sensitive,
      specific and accurate method and could be used for routine identification and
      quantification of small concentrations of diazepam and its metabolites in
      biological fluids.

PMID- 18041567
TI  - [Risk factors for nutritional status determination and indications for preventive
      nutrition therapy in hospitalized gastroenterological patients].
AB  - BACKGROUND/AIM: Risk factors for the intrahospital nutritional status worsening
      (NSW) have not been precisely defined in the literature. The objective was
      defining thoese factors among gastroenterological patients and defining the risk
      patients requiring a preventive nutritional therapy. METHODS: In 650
      gastroenterological patients, NSW was evaluated on the basis of reducing of the
      six parameters: body weight, body mass index (BMI), triceps skinfold thickness
      (TSF), mid-upper arm muscle circumference (MAMC), serum albumin level (ALB), and
      lymphocyte count (LYM). The influence on NSW was tested for 13 factors concerning
      characteristics of the patient, disease, and diagnostic procedures. Among the
      factors influencing significantly the NSW, primary and secondary risk factors
      were selected. After scoring of risk factors had been performed, the risk-score
      for NSW (RSNSW) was defined. The critical value of RSNSW which required
      preventive nutritional therapy was also calculated. RESULTS: The incidence of NSW
      was in the range 29.2%-57.9%. The presence of general complications and severe
      disease activity were considered as primary risk factors, whereas malignant
      disease, age above 71, hepato-billiary tract involvement, hospitalization longer
      than 14 days, and mobility worsening were considered as secondary risk factors.
      The best predictive value for the NSW was proved for the RSNSW > or = 6. Because
      of that, preventive nutritional therapy should be indicated in patients
      presenting with both primary risk factors or in patients presenting with one
      primary factor combined with three secondary risk factors at least. CONCLUSION:
      There are 7 risk factors for NSW in gastroenterological patients, but they are
      not of the same importance--two primary and five secondary risk factors can be
      differentiated. Preventive nutritional therapy is indicated only in patients
      having both primary risk factors or in those presenting with one primary risk
      factor combined with three secondary risk factors at least.

PMID- 18041568
TI  - [Botulinum toxin efficacy in the treatment of patients with spasmodic dysphonia].
AB  - BACKGROUND/AIM: Spasmodic dysphonia (DS) is a disabling speech disturbance
      appearing as the consequence of dystonic vocal folds contraction. Its
      intermittent appearance in the laryngeal muscles causes vocal function
      discontinuation. The quality of life of these patients is significantly
      disturbed. Surgical and a medical therapy appear to be inadequate and
      unsuccessful ones of no steady improvement. It is the botulinum toxin therapy
      that proved to be highly efficacious one, with the established improvement in 80
      100% of patients. The aim of our study was to evaluate the efficacy of botulinum
      toxin therapy in patients with SD and to show our preliminary results. METHODS:
      The study included 10 patients with adductor spasmodic dysphonia. After
      diagnostic procedures, botulinum toxin was applied either in one or both vocal
      folds, in doses of 12-16 units each. In our study we applied indirect technique
      originally developed by Hocevar and Pirtosek. Perceptive voice and speech
      analysis was performed prior to and after the instillation of botuline toxin as
      per structured Scale of pathological characteristics of voice and speech
      appearing in the spasmodic dysphonia. RESULTS: The majority of our patients
      experienced both subjective improvement and the improvement in the terms of the
      quality of life, Voice Henolicap Index--(VHI) that was rated as rather
      significant one (t = 3.562; p = 0.006). CONCLUSION: Regardless unquestionable
      improvement of definite phonation, further function restitution requires
      individual vocal therapy and psychotherapy. Vocal therapy includes structural
      vocal techniques which reduce degree of vocal tension and rapid changes in the
      power and the height of voice. Further investigations are necessary for the scope
      of the definition of a standardized therapeutically procedure for spasmodic
      dysphonia treatment which comprises multidisciplinary approach in diagnosis,
      therapy and treatment efficacy evaluation.

PMID- 18041569
TI  - [Evaluation of the depth of infiltration of urothelial carcinoma in the vesical
      wall obtained by transurethral intravesical echotomography].
AB  - BACKGROUND/AIM: Transitional cell carcinoma (TCC) is the most frequent tumor of
      the bladder and represents 95-98% of blader neoplasams and 2-3% of all carcinomas
      in the body. In urogenital oncology more frequent is only prostatic cancer.
      Evaluation of the depth of infiltration of urothelial carcinoma in the vesical
      wall represents the clinical base in treatment planning and prognosis. Clinical
      investigation and convential radiological procedures have a low level of accuracy
      in estimating the local growth of the tumor. The aims of our investigation were
      to determine the depth of infiltration of urothelial carcinoma in the vesical
      wall in the investigated group of patients by transurethral intravesical
      echotomography (TIE) and computerised tomography (CT scan) and to compare results
      obtained by both methods with pathohistological (PH) results, and, based on the
      difference of the results determine which method was more accurate in the
      evaluation of the depth of infiltration of urothelial carcinoma in the vesical
      wall. METHODS: Thirty patients with TCC of the bladder both genders, aged 51-81
      years were involved in our investigation. In all of these patients, radical
      cystectomy (RC) was performed. This was neccessary to provide the defintive PH
      result. Transurethral intravesical echotomography was performed by ultrasound
      scanner type 1846 Bruel and Kjaer, sond type 1850, and the CT scan was perfomed
      by Pace plus, General Electric, U.S.A. The specimen for the definitive PH result
      obtained by RC includes all standards of the TNM classification. RESULTS: Using
      CT scan, the most frequent was T1 stage (17 patients or 56.68%). Using TIE, the
      most frequent was T2 stage (22 patients or 73.33%). After RC the most frequent
      was T2 stage (21 patients or 70%). The Kolmogorov-Smirnov test, showed a high
      significant difference between the results obtained using CT and definitive PH
      results after RC. The same test showed no statistically significant difference
      between the results obtained using TIE and definitive PH results. The sensitivity
      and accurance of TIE compared to definitive PH results was 93.3%, but using CT it
      was only 33.3%. CONCLUSION: There was a significant difference between the
      results obtained using CT and TIE. The results obtained by TIE were in closer
      relation with the definitive PH results than the results obtained by CT scan. TIE
      provides more precise evaluation of the depth of infiltration of urothelial
      carcinoma in the vesical wall than CT scan. We conclude that the use of this
      procedure in local staging in TCC is justified and represents the clinical basis
      in the treatment planning and disease outcome prognosis.

PMID- 18041570
TI  - [Effect of hypertonic-hyperoncotic solution infusion on tissue perfusion during
      surgical treatment of the abdominal aorta].
AB  - BACKGROUND/AIM: Decreasing of arterial flow below the critical level leads to
      capillary endothelium edema and to further worsening of tissue perfusion.
      Hypertonic solution infusion provides mild and short plasma osmolality
      increasing, while colloidal solutions intensify that effect. The aim of this
      study was to investigate the effect of hypertonic-hyperoncotic solution (HH) on
      the organs perfusion during reconstructive surgical procedure on the abdominal
      aorta (AA). METHODS: The study included 40 patients submitted to AA
      reconstruction due to aneurysm or Leriche's syndrome. A clamp was put
      transversally to the aorta, under the outlets of the renal arterias. According to
      the solution received when a clamp was on the aorta, the patients were divided
      into two groups containing 20 patients each: the tested group (A) which received
      4 ml/kg of the solution (7.2% NaCl/10% dextran), and the control group (B) which
      received 0.9% NaCl. The study excluded the patients with the preoperative
      creatinine level more than 139 micromol/l, and ejection heart fraction less than
      40%. RESULTS: The mixed venous blood oxygen saturation increased from 73.3+/-7.33
      to 74.95+/-6.19% in the group A, while it decreased from 65.35+/-10.39 to 62.65+/
      10.42% in the group B (p = 0.001). The quantity of the provided oxygen in the
      group A increased significantly from 684.44+/-244.34 to 1362.45+/-2351.01 ml/min,
      while it decreased from 668.2+/-382.12 to 651.7+/-313.98 ml/min in the group B (p
      = 0.016). Alveolo-arterial difference in oxygen decreased from 23.12+/-14.74 to
      21.1+/-10 mmHg in the group A, while it increased from 23.79+/-15.22 to 26.33+/
      13.78 mmHg in the group B (p = 0.05). CONCLUSION: Satisfactory perfusion of
      organs during the AA surgery is obtained by using both HH and an isotonic
      solution. Due to maintaining the optimal values of the minute heart volume,
      saturation of vein blood blended with oxygen, and al-veolo-arterial difference in
      oxygen, it is recommended to use HH solution for reanimation of patients in
      declamping shock.

PMID- 18041571
TI  - [Influence of the primary malignant tumor site on the incidence and features of
      metastatic ovarian tumors].
AB  - BACKGROUND/AIM: Ovary is the organ of the female reproductive system most
      commonly affected by metastases. The aim of the study was to determine the
      frequency and features of metastatic ovarian tumors (MOT) depending on the site
      of the primary malignant tumor. METHODS: The study group consisted of 488
      patients with histopathologically confirmed ovarian cancers treated at the Clinic
      of Oncology, Clinical Center Nis, in the period from 1 January 1998 to 31
      December 2005. MOT were found in 41 patients. Regarding the site of the primary
      malignant tumor, those with secondary ovarian tumor were divided into two groups:
      group A--primary malignant tumor involving the genital organs (n = 30) and group
      B--primary malignant tumor of extragenital origin (n = 11). RESULTS: MOT were
      confirmed in 8.40% (41/488) of the patients. Secondary ovarian malignancies were
      the consequence of endometrial carcinoma spreading in 73.17%, breast carcinoma in
      19.51%, stomach carcinoma in 4.88% and colon carcinoma in 2.44% of the cases. No
      significant differences were found between the group A and group B by the factors
      of age, body mass index, parity and menopausal status. Contrary to the group A,
      metastatic tumors in the group B patients were more commonly asymptomatic (p <
      0.001), bilateral (p < 0.05), with larger ovarian diameter (p < 0.05), associated
      with ascites (p < 0.001) and abdominal metastases (p < 0.01), all of statistical
      significance. CONCLUSIONS: Metastatic tumors made up 8.40% of ovarian neoplasmas.
      With non-genital primary tumors, secondary ovarian deposits were frequently
      asymptomatic, bilateral, associated with larger ovarian diameter, ascites and
      abdominal metastatic deposits, compared to malignant tumors of genital origin.

PMID- 18041572
TI  - [Total bilateral hip arthroplasty in one surgical procedure].
AB  - BACKGROUND/AIM: Primary coxarthrosis occurs often in older population. There is
      possibility of implanting both endoprothesis simultaneosly in bilateral
      coxarthrosis which decreases hospitalisation and reduces the expences and
      possibility of complication that can occur during general anesthesia. The most
      serious indications for bilateral total hip arthroplasty in one procedure are
      younger patients with serious bilateral osteoarthrosis of the hips, without added
      diseases. Absolute contraindication is found in patients with persistent ductus
      arteriosus and septal defect. The aim of this study was to point out the
      possibility and advantages of a single-staged bilateral hip arthroplasty and
      introducing it in our orthopaedic practice. METHODS: The procedure was
      accomplished in 19 patients. The standard total hip arthroplasty surgical
      technique was performed, followed by the usual antibiotic and anticoagulant
      therapy. RESULTS: Only one complication--acetabular part instability we recorded,
      followed by luxation that was surgically managed. CONCLUSION: This procedure can
      be performed routinly in selected population and should be reserved for major
      medical centres capable to provide adequate postoperative care.

PMID- 18041573
TI  - [Electromagnetic field and osteogenesis].

PMID- 18041574
TI  - [New bearings in pharmacotherapeutic strategies: pharmacogenetics and gene
      therapy].

PMID- 18041575
TI  - [Coexistence of Hashimoto's thyroiditis and papillary thyroidal carcinoma with
      papillary carcinoma of thyreoglossal duct].
AB  - BACKGROUND: Simultaneous presence of Hashimoto's thyroiditis and papillary
      thyroidal carcinoma in thyroidal gland with papillary carcinoma association in
      thyroglossal duct is quite rare. The questions like where the original site of
      primary process, is where metastasis is, what the cause of coexisting of these
      diseasesis present a diagnostic dilemma. CASE REPORT: We presented a case of a 53
      year old female patient, with the diagnosis of Hashimoto's thyroiditis and
      symptoms of subclinical hypothyreosis and nodal changes in the right lobe of
      thyroidal gland, according to clinical investigation. Morphological examination
      of thyroidal gland, ultrasound examination and scintigraphy with technetium (Tc)
      confirmed the existence of nonhomogenic tissue with parenchyma nodular changes in
      the right lobe of thyroidal gland that weakly bonded Tc. Fine needle biopsy in
      nodal changes, with cytological analyses showed no evidence of atypical
      thyreocites. Hashimoto's thyroiditis was confirmed on the basis of the increased
      values of anti-microsomal antibodies, the high levels of thyreogobulin 117 ng/ml
      and TSH 6.29 microIU/ml. The operation near by the nodular change in the right
      lobe of thyroidal gland revealed pyramidal lobe spread in the thyroglossal duct.
      Total thyroidectomia was done with the elimination of thyroglossal duct. Final
      patohystological findings showed papillary carcinoma in the nodal changes pT2, N0
      and in the thyroglossal duct with the presence of Hashimoto's thyroiditis in the
      residual parenchyme of the thyroid gland. After the surgery the whole body
      scintigraphy with iodine 131 (131I) did not reveal accumulation of 131I in the
      body, while the fixation in the neck was 1%. After that, the patient was treated
      with thyroxin with suppression-substitution doses. CONCLUSION: Abnormality in
      embrional development of thyroidal tissue might be the source of thyroidal
      carcinoma or the way of spreading of metastasis of primary thyroidal carcinoma
      from thyroid gland. The cause of this process is most probably a hereditary
      mutation in RET oncogenes.

PMID- 18041577
TI  - Studies of natural products on treating neurological disorders in China.

PMID- 18041576
TI  - Drug-induced alterations in the extracellular signal-regulated kinase (ERK)
      signalling pathway: implications for reinforcement and reinstatement.
AB  - Drug addiction, characterized by high rates of relapse, is recognized as a kind
      of neuroadaptive disorder. Since the extracellular signal-regulated kinase (ERK)
      pathway is critical to neuroplasticity in the adult brain, understanding the role
      this pathway plays is important for understanding the molecular mechanism
      underlying drug addiction and relapse. Here, we review previous literatures that
      focus on the effects of exposure to cocaine, amphetamine, Delta(9)
      tetrahydrocannabinol (THC), nicotine, morphine, and alcohol on ERK signaling in
      the mesocorticolimbic dopamine system; these alterations of ERK signaling have
      been thought to contribute to the drug's rewarding effects and to the long-term
      maladaptation induced by drug abuse. We then discuss the possible upstreams of
      the ERK signaling pathway activated by exposure of drugs of abuse and the
      environmental cues previously paired with drugs. Finally, we argue that since ERK
      activation is a key molecular process in reinstatement of conditioned place
      preference and drug self-administration, the pharmacological manipulation of the
      ERK pathway is a potential treatment strategy for drug addiction.

PMID- 18041578
TI  - Prospect of neuroscience in China.
AB  - This article depicted how a young Chinese scientist got her training in China,
      how her training had impact on her scientific career in the US, and how she felt
      the prospect of Neuroscience in China.

PMID- 18041579
TI  - Antioxidant enzymatic system in neuronal and glial cells enriched fractions of
      rat brain after aluminum exposure.
AB  - The aim of this work was to investigate as to how neurons and glial cells
      separated from the brain cortex respond to oxidative stress induced by aluminum.
      Female SD rats were exposed to aluminum at the dose level of 100 mg/kg b.w. for 8
      weeks. Neuronal and glial cell-enriched fractions were obtained from rat cerebral
      cortex by sieving the trypsinated homogenate through a series of nylon meshes,
      followed by centrifugation on ficoll density gradient. Total glutathione content,
      glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-s
      transferase (GST) along with antioxidant enzymes superoxide dismutase (SOD),
      catalase were estimated in neuronal and glial-enriched fractions in both control
      (N-c and G-c) and aluminum exposed animals (N-a and G-a). Secondary products of
      lipid peroxidation that is MDA levels were estimated by measuring the (TBARS)
      levels. Our results indicate that TBARS levels were significantly higher in glial
      cell fraction of unexposed controls (Gc) than the neuronal cells (Nc).
      Correspondingly the glial cells had higher levels of GSH, GSSG, GPx and GST where
      as neurons had higher levels of catalase, SOD and GR. Following aluminum
      exposures significant increase in the TBARS levels was observed in neurons as
      compared to glial cells which also showed a significant decrease in SOD and
      catalase activity. The decrease in the TBARS levels in the glial cells could be
      related to the increase in the GSH levels, GR activity, and GST activity which
      were found to be increased in glial enriched fractions following aluminum
      exposure. The increase in activity of various enzymes viz GR, GST in glial cells
      as compared to neurons suggests that glial cells are actively involved in
      glutathione homeostasis. Our conclusion is that glial and neurons isolated from
      rat cerebral cortex show a varied pattern of important antioxidant enzymes and
      glial cells are more capable of handling the oxidative stress conditions.

PMID- 18041580
TI  - Maternal personal resources and children's socioemotional and behavioral
      adjustment.
AB  - The study examined the role of three maternal personal resources [sense of
      coherence (SOC), attachment style, and social/emotional feelings of loneliness]
      in explaining children's socioemotional adjustment (self-rated loneliness and
      SOC, and mother-rated child behavior) and children's (self-rated) secure
      attachment. The sample included 58 mother-child dyads (27 boys and 31 girls) aged
      8-11 years. Preliminary analyses indicated significant group differences between
      mothers with high or low scores on the two subscales of the attachment scale
      (i.e., avoidance and anxiety), on their SOC, and their social/emotional
      loneliness. Findings revealed that maternal SOC significantly contributed to all
      child socioemotional adjustment measures and attachment scores. In addition, the
      current findings demonstrated the role of maternal anxious attachment in
      explaining children's externalizing behaviors. Discussion focused on the unique
      value of maternal characteristics for understanding social and emotional
      adjustment among school-age children.

PMID- 18041581
TI  - Involvement of very long fatty acid-containing lactosylceramide in
      lactosylceramide-mediated superoxide generation and migration in neutrophils.
AB  - The neutral glycosphingolipid lactosylceramide (LacCer) forms lipid rafts
      (membrane microdomains) coupled with the Src family kinase Lyn on the plasma
      membranes of human neutrophils; ligand binding to LacCer activates Lyn, resulting
      in neutrophil functions, such as superoxide generation and migration (Iwabuchi
      and Nagaoka, Lactosylceramide-enriched glycosphingolipid signaling domain
      mediates superoxide generation from human neutrophils, Blood 100, 1454-1464, 2002
      and Sato et al. Induction of human neutrophil chemotaxis by Candida albicans
      derived beta-1,6-long glycoside side-chain-branched beta glycan, J. Leukoc. Biol.
      84, 204-211, 2006). Neutrophilic differentiated HL-60 cells (D-HL-60 cells)
      express almost the same amount of LacCer as neutrophils. However, D-HL-60 cells
      do not have Lyn-associated LacCer-enriched lipid rafts and lack LacCer-mediated
      superoxide-generating and migrating abilities. Here, we examined the roles of
      LacCer molecular species of different fatty acid compositions in these processes.
      Liquid chromatography-mass spectrometry analyses revealed that the very long
      fatty acid C24:0 and C24:1 chains were the main components of LacCer (31.6% on
      the total fatty acid content) in the detergent-resistant membrane fraction (DRM)
      from neutrophil plasma membranes. In contrast, plasma membrane DRM of D-HL-60
      cells included over 70% C16:0-LacCer, but only 13.6% C24-LacCer species. D-HL-60
      cells loaded with C24:0 or C24:1-LacCer acquired LacCer-mediated migrating and
      superoxide-generating abilities, and allowed Lyn coimmunoprecipitation by anti
      LacCer antibody. Lyn knockdown by siRNA completely abolished the effect of C24:1
      LacCer loading on LacCer-mediated migration of D-HL-60 cells. Immunoelectron
      microscopy revealed that LacCer clusters were closely associated with Lyn
      molecules in neutrophils and C24:1-LacCer-loaded D-HL-60 cells, but not in D-HL
      60 cells or C16:0-LacCer-loaded cells. Taken together, these observations suggest
      that LacCer species with very long fatty acids are specifically necessary for Lyn
      coupled LacCer-enriched lipid raft-mediated neutrophil superoxide generation and
      migration.

PMID- 18041582
TI  - A metabolomic study of brain tissues from aged mice with low expression of the
      vesicular monoamine transporter 2 (VMAT2) gene.
AB  - The vesicular monoamine transporter 2 (VMAT2) sequesters monoamines into synaptic
      vesicles in preparation for neurotransmission. Samples of cerebellum, cortex,
      hippocampus, substantia nigra and striatum from VMAT2-deficient mice were
      compared to age-matched control mice. Multivariate statistical analyses of (1)H
      NMR spectral profiles separated VMAT2-deficient mice from controls for all five
      brain regions. Although the data show that metabolic alterations are region- and
      age-specific, in general, analyses indicated decreases in the concentrations of
      taurine and creatine/phosphocreatine and increases in glutamate and N-acetyl
      aspartate in VMAT2-deficient mouse brain tissues. This study demonstrates the
      efficacy of metabolomics as a functional genomics phenotyping tool for mouse
      models of neurological disorders, and indicates that mild reductions in the
      expression of VMAT2 affect normal brain metabolism.

PMID- 18041583
TI  - Variability in cardiovascular control: the baroreflex reconsidered.
AB  - Although blood pressure control is often viewed as a paradigmatic example of a
      "homeostatic" biological control system, blood pressure levels can fluctuate
      considerably over shorter and longer time scales. In modern signal analysis,
      coherence between heart rate and blood pressure variability is used to estimate
      baroreflex gain. However, the shorter the measurement period, the more
      variability this gain factor reveals. We review evidence that this variability is
      not due to the technique used for the estimation, but may be an intrinsic
      property of the circulatory control mechanisms. The baroreflex is reviewed from
      its evolutionary origin, starting in fishes as a reflex mechanism to protect the
      gills from excessively high pressures by slowing the heart via the
      (parasympathetic) vagus nerve. Baroreflex inhibition of cardiovascular
      sympathetic nervous outflow is a later development; the maximally possible extent
      of sympathetic activity probably being set in the central nervous system by
      mechanisms other than blood pressure per se. In the sympathetic outflow tract not
      only baroreflex inhibition but also as yet unidentified, stochastic mechanisms
      decide to pass or not pass on the sympathetic activity to the periphery. In this
      short essay, the "noisiness" of the baroreflex as nervous control system is
      stressed. This property is observed in all elements of the reflex, even at the-
      supposedly--most basic relation between afferent receptor nerve input and
      efferent--vagus--nerve output signal.

PMID- 18041584
TI  - Cerebral autoregulation: from models to clinical applications.
AB  - Short-term regulation of cerebral blood flow (CBF) is controlled by myogenic,
      metabolic and neurogenic mechanisms, which maintain flow within narrow limits,
      despite large changes in arterial blood pressure (ABP). Static cerebral
      autoregulation (CA) represents the steady-state relationship between CBF and ABP,
      characterized by a plateau of nearly constant CBF for ABP changes in the interval
      60-150 mmHg. The transient response of the CBF-ABP relationship is usually
      referred to as dynamic CA and can be observed during spontaneous fluctuations in
      ABP or from sudden changes in ABP induced by thigh cuff deflation, changes in
      posture and other manoeuvres. Modelling the dynamic ABP-CBFV relationship is an
      essential step to gain better insight into the physiology of CA and to obtain
      clinically relevant information from model parameters. This paper reviews the
      literature on the application of CA models to different clinical conditions.
      Although mathematical models have been proposed and should be pursued, most
      studies have adopted linear input-output ('black-box') models, despite the
      inherently non-linear nature of CA. The most common of these have been transfer
      function analysis (TFA) and a second-order differential equation model, which
      have been the main focus of the review. An index of CA (ARI), and frequency
      domain parameters derived from TFA, have been shown to be sensitive to
      pathophysiological changes in patients with carotid artery disease, stroke,
      severe head injury, subarachnoid haemorrhage and other conditions. Non-linear
      dynamic models have also been proposed, but more work is required to establish
      their superiority and applicability in the clinical environment. Of particular
      importance is the development of multivariate models that can cope with time
      varying parameters, and protocols to validate the reproducibility and ranges of
      normality of dynamic CA parameters extracted from these models.

PMID- 18041585
TI  - An overview of HIV and chronic viral hepatitis co-infection.
AB  - Combination antiretroviral therapy often controls HIV disease, may indirectly
      slow HCV progression, and creates an immune environment which may optimize HCV
      drug therapy response. Monitoring for antiretroviral-related liver adverse events
      is vital. However, this complication infrequently causes clinically significant
      liver toxicity. HCV antiviral therapy should, in most cases, be reserved for
      those abstaining from alcohol and achieving HIV RNA suppression and immune
      restoration on combination antiretroviral therapy or for those with nadir CD4
      counts above 350 cells/mul. Given the high prevalence of HBV and HCV co
      infection, chronic viral hepatitis will influence the health and treatment of HIV
      infected individuals for the foreseeable future.

PMID- 18041586
TI  - Protective effects of diets supplemented with omega-3 polyunsaturated fatty acids
      and calcium against colorectal tumor formation.
AB  - This study is to evaluate the effect of dietary omega-3 polyunsaturated fatty
      acid (omega-3 PUFA) and/or calcium supplementation on colon tissue of the
      carcinogenic N-methyl-N-nitrosurea (NMU)-injected rats and to investigate this
      effect by the assessment of the oxidative stress. The rats were divided into four
      groups: those fed with a standard diet, with a diet supplemented by omega-3 PUFA,
      those fed with a diet with calcium, and those fed with a standard diet with the
      combination of omega-3 PUFA and calcium. Rats were injected with an intrarectal
      NMU. After 32 weeks, colon tissue specimens and plasma were taken to
      histopathologically investigate and analyze tissue superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-px) activities and erythrocyte MDA levels. The tumor
      incidences in supplemented-diet groups II and IV were found to be significantly
      lower when compared with those of the controls (P < 0.05). Superoxide dismutase
      and glutathione peroxidase antioxidative enzyme activities in colorectal tissue
      were increased in the study groups when compared with control rats (P < 0.001)
      and MDA levels were significantly lower than in the controls (P < 0.001) while
      the levels in group IV were rather decreased than those in group III (P = 0.011).
      These results suggest that the dietary supplementation of PUFA and/or calcium may
      be useful in the prevention of colorectal tumor formation.

PMID- 18041588
TI  - Psychogenic nonepileptic seizures.
AB  - Neurological, neurodiagnostic, and neuropsychological aspects of psychogenic
      nonepileptic seizures (PNES) are reviewed, including psychosocial, psychiatric,
      cognitive, and MMPI-2 findings.

PMID- 18041587
TI  - Sensitivity to phonological similarity within and across languages.
AB  - The influence of phonological similarity on bilingual language processing was
      examined within and across languages in three experiments. Phonological
      similarity was manipulated within a language by varying neighborhood density, and
      across languages by varying extent of cross-linguistic overlap between native and
      non-native languages. In Experiment 1, speed and accuracy of bilinguals' picture
      naming were susceptible to phonological neighborhood density in both the first
      and the second language. In Experiment 2, eye-movement patterns indicated that
      the time-course of language activation varied across phonological neighborhood
      densities and across native/non-native language status. In Experiment 3, speed
      and accuracy of bilingual performance in an auditory lexical decision task were
      influenced by degree of cross-linguistic phonological overlap. Together, the
      three experiments confirm that bilinguals are sensitive to phonological
      similarity within and across languages and suggest that this sensitivity is
      asymmetrical across native and non-native languages and varies along the
      timecourse of word processing.

PMID- 18041589
TI  - Reading development and dyslexia in a transparent orthography: a survey of
      Spanish children.
AB  - Spanish-speaking children learn to read words printed in a relatively transparent
      orthography. Variation in orthographic transparency may shape the architecture of
      the reading system and also the manifestation of reading difficulties. We tested
      normally developing children and children diagnosed with reading difficulties.
      Reading accuracy was high across experimental conditions. However, dyslexic
      children read more slowly than chronological age (CA)-matched controls, although,
      importantly, their reading times did not differ from those for ability-matched
      controls. Reading times were significantly affected by frequency, orthographic
      neighbourhood size and word length. We also found a number of significant
      interaction effects. The effect of length was significantly modulated by reading
      ability, frequency and neighbourhood. Our findings suggest that the reading
      development of dyslexic children in Spanish is delayed rather than deviant. From
      an early age, the salient characteristic of reading development is reading speed,
      and the latter is influenced by specific knowledge about words.

PMID- 18041590
TI  - Molecular genetic events in gastrointestinal and pancreatic neuroendocrine
      tumors.
AB  - Gastrointestinal and pancreatic neuroendocrine tumors originate from the cells of
      the diffuse endocrine system. Their molecular genetic mechanism of development
      and progression is complex and remains largely unknown, and they are different in
      genetic composition from the gastrointestinal epithelial tumors. The current
      literature suggests that multiple genes are involved in their tumorigenesis with
      significant differences for tumors of different embryological derivatives:
      foregut, midgut and hindgut. The MEN1 gene is involved in initiation of 33% of
      foregut gastrointestinal neuroendocrine tumors. 18q defects are present almost
      exclusively in mid/hindgut neuroendocrine tumors. X-chromosome markers are
      associated with malignant behavior in foregut tumors only. Analysis of poorly
      differentiated neuroendocrine carcinomas of any site demonstrates high
      chromosomal instability and frequent p53 alterations similar to other poorly
      differentiated carcinomas. Several factors played a limiting role in the
      molecular studies published to date: the tumors are rare and heterogeneous, it is
      difficult to predict their behavior and prognosis, and several different tumor
      classifications are used by the investigators in the studies. Future studies need
      to evaluate molecular genetic composition of large series of gastrointestinal and
      pancreatic neuroendocrine tumors of each specific tumor type. Understanding of
      specific genetic alterations characteristic for gastrointestinal and pancreatic
      neuroendocrine tumors might lead to their improved diagnosis, morphologic and
      molecular characterization and treatment.

PMID- 18041591
TI  - A primary right atrium paraganglioma in a 15-year-old patient.
AB  - Thoracic pheochromocytomas account for less than 2% of reported cases, while
      primary cardiac paragangliomas are even rare. The following case illustrates a 15
      year-old patient with primary right atrium paraganglioma. This patient was
      referred for paroxysmal hypertension and excessive perspiration. Pheochromocytoma
      was suspected and then confirmed by very high serum nor-metanephrine which
      increased more than 30-fold above the upper limit of normal. 131I
      metaiodobenzylguanidine (MIBG) scintigraphy showed high uptake only in the middle
      mediastinum, but not in the adrenal glands or elsewhere. Both contrast CT and
      gated MRI of the chest disclosed a 5.0 x 4.0 cm2 mass in the right atrium.
      Coronary angiography demonstrated the mass with feeding vessels from the right
      coronary artery. When the patient's blood pressure was well controlled with
      doxazosin and metoprolol, surgery was then performed. A 6.0 x 4.9 x 4.0 cm3 round
      solid right atrium paraganglioma weighing 41.7 g was resected. The second day
      after surgery, serum nor-metanephrine and urinary noradrenaline levels dropped
      rapidly to normal range, and the patient was free of clinical symptoms with
      normal BP. Postoperative cardiac function, as measured by echocardiogram, was
      normal. Although cardiac paraganglioma may be difficult to resect, it can be
      cured.

PMID- 18041592
TI  - Comparison of manual and automatic (MagNA Pure) isolation methods of total RNA
      from adipose tissue.
AB  - AIM: Comparison of manual and automatic (MagNA Pure) isolation methods of total
      RNA from adipose tissue with respect to its quality and recovery factor.
      MATERIAL: 120 human subcutaneous adipose tissue samples (about 100 mg/sample)
      were collected from patients during surgical operations. The tissue sample was
      stabilized in RNAlater (QIAGEN GmbH, Germany). METHODS: Total RNA was extracted
      by the following kits: Rneasy Protect Mini, Rneasy Lipid Tissue (QIAGEN GmbH,
      Germany) and MagNA Pure Compact RNA Isolation (Tissue) for MagNA Pure Compact
      Instrument (Roche Diagnostics GmbH, Germany). RESULTS: The average RNA yields
      with Rneasy Lipid Tissue kits were about two-fold higher in comparison with the
      Rneasy Protect Mini kit. When the MagNA Pure Compact System was used, RNA yields
      from the same sample were more uniform compared with manual systems. It was also
      more convenient and less time-consuming than the manual approach. No DNA
      contamination of total RNA samples was detected except for samples isolated by
      Rneasy Protect Mini Kit. CONCLUSION: Rneasy Lipid Tissue Kit and MagNA Pure
      Compact RNA Isolation Kit (Tissue) provide RNA samples of high quantity, purity
      and PCR amplificability. RNA samples are suitable for further processing using
      methods of molecular biology.

PMID- 18041593
TI  - [Diabetes and the heart. Abstracts of the 35th Annual Meeting of the Austrian
      Society of Diabetes. November 29-December 1, 2007. Innsbruck, Austria].

PMID- 18041594
TI  - 2007--a very successful year for "Anxiety, Stress and Coping".

PMID- 18041595
TI  - Editorial: Twenty-five years on ...

PMID- 18041596
TI  - Effect of consumer cooking on furan in convenience foods.
AB  - The effect of domestic preparation regimes on the level of the heat-formed
      toxicant furan was studied to provide useful information for exposure assessment
      and advice for manufacturers and consumers. Foods were cooked in a saucepan on a
      gas hob or microwaved and furan was determined by headspace sampling with gas
      chromatography-mass spectrometry. In general, furan levels did not decrease as
      much when foods were cooked in a microwave oven when compared with the same foods
      cooked in a saucepan. Furan levels decreased in most canned and jarred foods
      after heating in a saucepan. Low levels of furan in soups in cartons were not
      changed by any procedure. Furan decreased slightly in foods on standing before
      consumption, but did so more rapidly on stirring. The levels also decreased
      slightly when foods were left to stand on plates; this observation is attributed
      to the volatility of furan.

PMID- 18041597
TI  - Absorption, distribution and elimination of fumonisin B(1) metabolites in weaned
      piglets.
AB  - The absorption, distribution and elimination of fumonisin B(1) (and B(2)) after
      oral administration of Fusarium verticillioides (MRC 826) fungal culture, mixed
      into the experimental feed for 10 days, was studied in weaned barrows. In order
      to determine the absorption of FB(1) from the feed marked by chromium oxide, a
      special T-cannula was implanted into the distal part of pigs' ileum. During the
      feeding of toxin-containing diet (45 mg FB(1) kg(-1)) and until the tenth day
      after the end of treatment, the total quantity of urine and faeces was collected
      and their toxin content analysed. At the end of the trial, samples of lung,
      liver, kidney, brain, muscle, and fat were also collected and their fumonisin
      content analysed by LC-MS. The fumonisins appeared to decrease the reduced
      glutathione content in blood plasma and red blood cell haemolysate, possibly
      associated with in vivo lipid peroxidation. From a data set of 80 individual data
      and the concentration and rate of C(r) and fumonisins (FB(1), partially
      hydrolysed FB(1) and aminopentol) in the chymus, it could be established that the
      accumulative absorption of fumonisin B(1) was 3.9% +/- 0.7%. In the chymus, the
      FB(1) conversions into aminopentol and partially hydrolysed FB(1) were 1.0 and
      3.9%, respectively. The degree of metabolism in faeces was variable, although the
      main product was the partially hydrolysed form, with very small amounts of the
      aminopentol moiety being recovered. In the investigated tissues the FB(1)
      conversion to aminopentol and partially hydrolysed FB(1) was 30 and 20%,
      respectively.

PMID- 18041598
TI  - Fenvalerate residue level and dissipation in tea and in its infusion.
AB  - Fenvalerate is a non-systemic insecticide/acaricide used in controlling a wide
      range of pests, including those resistant to organochlorine, organophosphorus and
      carbamate insecticides. The study investigated the dissipation behaviour (residue
      level) of fenvalerate in tea and its transfer during infusion. Fenvalerate was
      applied on tea crop at two dosages, 100 and 200 g a.i. ha(-1) (recommended and
      double the recommended) in the dry and wet seasons under field conditions.
      Samples (green tea shoots, made tea, its infusion and spent leaves) were analysed
      for fenvalerate by high-performance liquid chromatography using diode array
      detection. The residue dissipated faster in the wet season than in the dry
      season. Seven days after the treatment (normal round of plucking) the residues
      observed in the green shoots at the two dosages were 0.5 +/- 0.01, 1.1 +/- 0.01
      and 0.4 +/- 0.02, 0.9 +/- 0.01 mg kg(-1) in the dry and wet seasons,
      respectively. During processing of green tea shoots to made tea a 30-40% loss of
      residue was observed. The transfer of residue from made tea to infusion was in
      the range 10-30% for both seasons, whereas 50-70% of the residues remained in the
      spent leaves. However, the degradation rate in both seasons followed first-order
      kinetics. The half-lives were in the range of 2-3 days for green shoots and made
      tea in both seasons.

PMID- 18041599
TI  - Development of monoclonal antibodies for the fusarin mycotoxins.
AB  - The fusarins are a group of mycotoxins produced by fungi that commonly infest
      cereal crops, in particular by the fungus Fusarium verticillioides. This group of
      compounds is characterized by a substituted 2-pyrrolidone ring attached to a 12
      carbon polyunsaturated backbone. Several of the fusarins contain an epoxide
      substitution on the pyrrolidone ring and are highly mutagenic. This paper
      describes the development of seven monoclonal antibodies and immunoassays for
      detecting fusarins C and A. Fusarin C was isolated and conjugated to ovalbumin to
      produce the immunogen. Competitive indirect enzyme-linked immunosorbent assays
      (CI-ELISAs) were developed based upon the isolated monoclonal antibodies. The
      concentrations of fusarin C able to inhibit colour development by 50% (IC(50)) in
      CI-ELISAs were 1.0, 2.0, 3.6, 23.4, 28.9, 31.4, and 66.7 ng ml(-1) for clones 1
      38, 1-30, 1-5, 1-7, 1-43, 1-25, and 1-21, respectively. Cross-reactivity with
      fusarin A was 44.8, 51.4, 41.1, 174.0, 62.6, 78.2, and 98.0% for clones 1-38, 1
      30, 1-5, 1-7, 1-43, 1-25, and 1-21, respectively. Given the sensitivity of these
      antibodies for fusarins it is expected that, with further development, they may
      be useful for detecting fusarins at relevant levels in foods.

PMID- 18041600
TI  - Sources of contamination by polycyclic aromatic hydrocarbons in Spanish virgin
      olive oils.
AB  - The presence of polycyclic aromatic hydrocarbons (PAHs) in virgin olive oils
      results from contamination on olive skins and the oil itself during processing.
      Determination of nine PAHs was carried out by isolation of the hydrocarbon
      fraction and subsequent clean-up by solid phase extraction, followed by RP-HPLC
      analysis using a programmable fluorescence detector. Contamination of olive skins
      depends directly on environmental pollution levels and inversely on fruit size.
      In the oil mill, PAHs levels were increased by contamination from combustion
      fumes during the extraction process. Other procedures, such as washing or talc
      addition during extraction, did not affect PAHs levels. High concentrations of
      PAHs were only found as a consequence of accidental exposure to contamination,
      such as direct contact of olives with diesel exhaust and oil extraction in a
      polluted environment.

PMID- 18041603
TI  - Unertan syndrome: a case series demonstrating human devolution.
AB  - A large family with six individuals exhibiting the Unertan syndrome (UTS) was
      identified residing in southern Turkey. All of the individuals had mental
      impairments and walked on all four extremities. The practice of intra-familial
      marriages suggested that the UTS may be an autosomal recessive disorder, similar
      to previously described cases. The inferior portions of the cerebellum and vermis
      were absent as evidenced by MRI and CT scans. The height and head circumference
      of those affected were within normal ranges. Barany's test suggested normal
      vestibular system function. The subjects could not name objects or their close
      relatives. The males (n = 4) could understand simple questions and commands, but
      answered questions with only one or two sounds. The females (n = 2) were superior
      to the males with respect to language skills and walking, suggesting an
      association between walking and speaking abilities. One male exhibited three
      walking patterns at the same time: quadripedal, tiptoe, and scissor walking.
      Another male used two walking styles: quadripedal and toe-walking. It is
      emphasized that there are important differences between the UTS and the
      disequilibrium syndrome. It is suggested that the inability to walk upright in
      those affected with the UTS may be best explained by a disturbance in lateral
      balance mechanisms, without being related to the cerebello-vestibular system. An
      interruption of locomotor development during the transition from quadripedality
      to bipedality may result in habitual walking on all four extremities and is
      normal in some children. Because quadripedal gait is an ancestral trait,
      individuals with the UTS, exhibiting a manifestation of reverse evolution in
      humans, may be considered an experiment of nature, useful in understanding the
      mechanisms underlying the transition from quadripedality to bipedality during
      human evolution. The proposed mutant gene or gene pool playing a role in human
      quadrupedality may also be responsible for human bipedality at the same time.
      Herein there is no intent to insult or injure; rather, this report is an endeavor
      to better understand human beings. Supplementary materials are available for this
      article. Go to the publisher's online edition of International Journal of
      Neuroscience for the following free supplemental resource(s): video clips.

PMID- 18041604
TI  - Abnormal ERPs and high frequency bands power in multiple sclerosis.
AB  - Event-related potentials (ERPs) and power spectral density (PSD) were registered
      during an auditory-oddball paradigm in 11 MS patients. These patients showed a
      decrease in the amplitude of P2 and N2 components and a delayed P3 latency
      compared to control subjects suggesting that the attentional orienting mechanism
      in the auditory modality is affected in MS. The PSD analysis showed that MS
      patients exhibited an increased power in beta and gamma bands. The combined
      analysis of frequency and time domain suggested diverse phenomena that occurred
      in the MS patient group related with the EEG background or the motivational
      status.

PMID- 18041605
TI  - The effect of aripiprazole on prepulse inhibition of the startle response in
      normal and hyperdopaminergic states in rats.
AB  - This study compared the D(2) partial agonists, aripiprazole, (R(+)-terguride; S(
      )-3-(3-hydroxyphenyl)-N-n-propylpiperidine [S(-)-3-PPP]; 7-[3-[4-(2,3
      dimethylphenyl)piperazinyl]propoxy]-2(1H)-quinolinone [OPC-4392]) and D(2)
      antagonists (haloperidol, olanzapine, clozapine, risperidone, and quetiapine) on
      prepulse inhibition (PPI) of the startle response, and the ability to reverse
      apomorphine-induced deficits in the PPI response. Aripiprazole did not
      essentially affect PPI in naive rats but dose-dependently restored apomorphine
      induced PPI disruption. R(+)-terguride restored PPI disruption but suppressed PPI
      significantly in naive rats, S(-)-3-PPP partially restored whereas OPC-4392 did
      not restore PPI disruption. Haloperidol and risperidone restored PPI disruption
      whereas olanzapine and quetiapine partially restored PPI disruption and clozapine
      had no restorative effect. In conclusion, aripiprazole, unlike other
      antipsychotic agents, failed to suppress PPI significantly and restored PPI
      disruption.

PMID- 18041606
TI  - Modulation of cognitive performance and mood by aromas of peppermint and ylang
      ylang.
AB  - This study provides further evidence for the impact of the aromas of plant
      essential oils on aspects of cognition and mood in healthy participants. One
      hundred and forty-four volunteers were randomly assigned to conditions of ylang
      ylang aroma, peppermint aroma, or no aroma control. Cognitive performance was
      assessed using the Cognitive Drug Research computerized assessment battery, with
      mood scales completed before and after cognitive testing. The analysis of the
      data revealed significant differences between conditions on a number of the
      factors underpinning the tests that constitute the battery. Peppermint was found
      to enhance memory whereas ylang-ylang impaired it, and lengthened processing
      speed. In terms of subjective mood peppermint increased alertness and ylang-ylang
      decreased it, but significantly increased calmness. These results provide support
      for the contention that the aromas of essential oils can produce significant and
      idiosyncratic effects on both subjective and objective assessments of aspects of
      human behavior. They are discussed with reference to possible pharmacological and
      psychological modes of influence.

PMID- 18041607
TI  - Repeat test scores on neurobehavioral measures over an eight-year period in a
      sample of Portuguese children.
AB  - Normative data were collected on a sample of 503 Portuguese children who were
      taking part in a dental study. At the outset, the children were aged 8-11.9
      years, with an average of just over 10. A standard battery of neurobehavioral
      tests covering learning and memory, visual-motor function, and attention was
      administered at baseline and during seven subsequent years. Normative test data
      are presented separately by gender and by age at study inception (younger versus
      older). Results provide normative data for use in clinical settings, where
      dissociations in performance between cognitive domains need to be identified for
      diagnostic and therapeutic purposes.

PMID- 18041608
TI  - Chronic prenatal depression and neonatal outcome.
AB  - Four hundred and thirty pregnant women were recruited at approximately 22 weeks
      gestation at prenatal clinics. Of these, 86 (20%) were diagnosed as depressed.
      The women were seen again at approximately 32 weeks gestation and after delivery.
      Chronicity of depression was evidenced by continuing high depression scores in
      those women diagnosed as depressed. Comorbid problems were chronically high
      anxiety, anger, sleep disturbance, and pain scores. Less optimal outcomes for the
      depressed women included lower gestational age and lower birthweight of their
      newborns.

PMID- 18041610
TI  - Time reproduction disturbances in ADHD children: an ERP study.
AB  - Sixteen ADHD children and a control group were asked to reproduce the varying
      time duration of successively presented visual stimuli. Time estimation was
      poorer in ADHD children, who showed more impulsive errors. ERPs exhibited similar
      grand-mean waveforms for both groups during the estimating period, but they were
      significantly different during the reproducing stage, when an early positive wave
      over frontal regions characterized the control group, interpreted as memory
      guided motor output, followed by a slow negativity probably reflecting an
      inhibitory motor closure process, both probably involving central executive
      networks that seem to be improperly activated in ADHD children.

PMID- 18041609
TI  - The effect of progesterone on total brain tissue sialic acid levels in
      experimental epilepsy.
AB  - Epilepsy, the most common neurological disorder worldwide, changing cellular
      interactions and connectivity may have effects on sialic acid levels. A total of
      80 mice were separated into 8 groups: the sham, control, pentylentetrazole (PTZ),
      PTZ plus progesterone, five dose progesterone, single dose progesterone,
      kindling, and kindling plus progesterone groups. Brains of each mice were
      extracted and were divided into five parts. The sialic acid levels were
      significantly different between the groups and also in the subgroups. The results
      suggested that progesterone may have an anti-seizure effect by decreasing sialic
      acid levels in mice. Further studies are needed to evaluate the role of
      progesterone on sialic acid levels and its role in the epilepsy pathogenesis.

PMID- 18041611
TI  - Relationship between dysgeusia and dysesthesia in stroke patients.
AB  - This study investigated the relationship between dysgeusia and dysesthesia in
      stroke patients and evaluated the effect of carbamazepine therapy. Twenty-four
      patients with dysesthesia of the face, oral cavity, or tongue were divided into
      two groups: with and without subjective dysgeusia. Taste thresholds were
      objectively evaluated using the filter-paper taste test and electrogustometry.
      There was no significant difference in taste thresholds between the two groups.
      Carbamazepine had an effect on subjective dysgeusia in four of the eight treated
      patients. Dysgeusia with dysesthesia in stroke patients might be caused by
      disorders of the somatosensory pathway rather than disorders of the gustatory
      pathway.

PMID- 18041612
TI  - A prefrontal ERP involved in decision making during visual duration and size
      discrimination tasks.
AB  - Recently, a late positive component (LPCt) with prefrontal dominance was
      identified in a duration discrimination task as a marker of decision-making
      processes (Paul et al., 2003). In the present study, LPCt amplitudes and
      latencies were measured in visual and size discrimination tasks for the purpose
      of determining the selectivity of this phenomenon. LPCt amplitudes were larger
      and latencies shorter for longer stimulus pairs, at a time of maximal behavioral
      performances. Wave amplitudes were also larger for smaller stimuli, but were not
      directly related to behavioral performances. These results indicate that the LPCt
      is not specific to temporal discrimination but can reflect more general decision
      making processes.

PMID- 18041613
TI  - Apolipoprotein E phenotype in demented patients in Greek population.
AB  - Apolipoprotein E is a plasma protein, involved in the transport of lipids and
      their metabolism. The aim of this investigation was to correlate the ApoE
      phenotypes with the type and the severity of dementia in Greek demented patients.
      The investigation revealed that 72% of the patients have the E3/3 phenotype, but
      only 11% of them demonstrated the E3/2; 13% of the patients have the E4/3
      phenotype and only 4% of them demonstrated the phenotype E4/4. The most severely
      demented patients corresponded to e4 allele. The present results indicate that
      the most common ApoE phenotype in Greek demented patients is E3/3.

PMID- 18041614
TI  - The omitted stimulus potential is related to the cognitive component of reaction
      time.
AB  - Omitted stimulus potentials (OSP) are waves that are considered to involve
      moderately high-level processing, but their relation to the cognitive, premotor
      component of reaction time (PMRT) to an omitted stimulus has not been examined.
      This relationship was tested in 20 participants who responded to an auditory
      omitted stimulus occurring in fast (7 Hz) and slow (.5 Hz) frequency trains while
      electrophysiological recordings provided measures of the OSP and EMG. In accord
      with the hypothesis, the time between the onset of the OSP and the EMG was
      strongly correlated to PMRT under both stimulus frequency conditions.

PMID- 18041615
TI  - Coherent motion, magnocellular sensitivity and the causation of dyslexia.
AB  - The central tenet of the magnocellular deficit theory of dyslexia is that
      dyslexia is caused by a magnocellular deficit. A number of investigators have
      found deficiencies in visual coherent motion perception among dyslexic readers.
      These deficiencies have been attributed to magnocellular deficits, which means
      that they directly reflect the cause of dyslexia. However, similar perceptual
      deficiencies have been found in association with autism, Williams's syndrome,
      hemiplegia, and schizophrenia. These findings appear to undermine at least one of
      the following claims: (1) that a magnocellular deficit is the cause of dyslexia,
      and (2) that coherent motion is a reliable test of magnocellular sensitivity.

PMID- 18041617
TI  - Isolation of bicarbonate from equine urine for isotope ratio mass spectrometry.
AB  - Sodium bicarbonate administration to horses prior to competition in order to
      enhance the buffer capacity of the organism is considered as a doping offence.
      The analysis of the isotopic composition of urinary bicarbonate/CO(2) (TCO(2))
      may help to identify an exogenous bicarbonate source, as technical sodium
      bicarbonate exhibits elevated delta(13)C values compared with urinary total
      carbon. The isolation of TCO(2) from 60 equine urine samples as BaCO(3) followed
      by an isotopic analysis shows a significant variability of delta(13)C for TCO(2)
      of more than 10 per thousand. The delta(13)C of total carbon and TCO(2) seem to
      reflect different proportions of C3 and C4 plant material in the diet. The
      isotopic analysis of different mixtures of technical NaHCO(3) and equine urine
      shows that TCO(2) can be easily isolated without major isotopic fractionation;
      however, attention has to be paid to the storage time of urine samples, as a
      shift of delta(13)C of TCO(2) to lower values may occur.

PMID- 18041618
TI  - Determination of delta13 CV-PDB and delta15NAIR values of cocaine from a big
      seizure in Germany by stable isotope ratio mass spectrometry.
AB  - In this study, delta(13)C(V- PDB) and delta(15)N(AIR) values of 132 cocaine
      samples from a big seizure in Germany in 2002 were determined using elemental
      analyser isotope ratio mass spectrometry. The 1.2 tons of cocaine were packed in
      1 kg packages and the cocaine bricks inside these packages showed certain logos.
      Twenty different logos could be identified. Results show a large variability
      among some samples, for delta(15)N(AIR) values ranging from-17 to -2 per
      thousand. Furthermore, the possibility of linking samples with the same logo was
      checked. The results show that, in general, there is no relationship between the
      determined isotope ratio and a certain logo.

PMID- 18041619
TI  - Stable nitrogen isotopes in essential versus non-essential amino acids of
      different plankton size fractions.
AB  - The stable nitrogen isotope values (delta(15)N) of the essential amino acid (EAA)
      leucine and the delta(15)N values of six non-essential amino acids (NEAAs) from
      plankton size fractions from the South China Sea (SCS) were analysed. Data from
      the SCS were collected during two cruises in July 2003 and 2004 onboard of RV
      Nghien Cuu Bien. The delta(15)N values of alanine, aspartic acid, glutamic acid
      and leucine increased with size at all sites. The delta(15)N of glycine did not
      increase with size, the delta(15)N of tyrosine increased with size only at
      offshore stations and the delta(15)N of proline increased with size only at
      inshore stations. We found highly significant correlations between the delta(15)N
      ratios of leucine to the delta(15)N ratios of glutamic acid, proline, alanine,
      tyrosine and aspartic acid at oligotrophic sites of enhanced nitrogen fixation.
      In contrast thereto these correlations were less distinct or absent at more
      eutrophic sites of low nitrogen fixation. A comparison with an independent data
      set from the tropical North Atlantic revealed intriguing similar patterns. We
      interpret these patterns as result of the connected metabolism of EAA and NEAA in
      zooplankton at sites of nitrogen limitation.

PMID- 18041620
TI  - Regional and temporal (1992-2004) evolution of air-borne sulphur isotope
      composition in Saxony, southeastern Germany, central Europe.
AB  - The isotopic composition of air-borne sulphur was investigated in Saxony,
      Southeast Germany--a region with formerly very high atmospheric SO(2)
      concentrations. In addition, data from various authors were compiled for
      different Saxonian locations, spanning from 1992 to 2004, i.e., a time of
      decreasing SO(2) concentrations in the atmosphere. There were no obvious temporal
      changes in the mean delta(34)S value of bulk precipitation. However, the
      variability of monthly mean delta(34)S values decreased. The mean sulphur isotope
      composition of sulphate from bulk precipitation after the year 2000 converges in
      Saxony towards 4-5 per thousand, with similar values for different locations.
      Mean values of different forms of sulphur show the following enrichment order:
      delta(34)S of SO(2) < delta(34)S of weathering crusts < or =delta(34)S of
      sulphate from bulk precipitation < or =delta(34)S of dust. Judging from local
      differences on sulphate crusts and corresponding isotope values of sources, the
      delta(34)S value of SO(2) as well as for crusts mainly reflects local point
      sources. The mean delta(34)S value of bulk precipitation represents more
      regionally well-mixed SO(2) sources and is therefore an ideal tool for monitoring
      regional atmospheric change.

PMID- 18041621
TI  - Comparison of monthly and daily isotopic composition of precipitation in the
      coastal area of Slovenia.
AB  - The stable isotopic composition (delta(2)H and delta(18)O) of short-term (daily)
      precipitation collected from October 2002 to September 2003 at two stations in a
      coastal, karstic area in south-western Slovenia was investigated. In addition,
      monthly composite samples were collected and analysed for comparison with amount
      weighted monthly means. The delta(2)H and delta(18)O values obtained show a wide
      range and reflect seasonal climatic variations. Deuterium excess and local
      meteoric water lines (LMWLs) were determined and cumulative frequency analysis
      and coincidence tests were performed. The statistical coincidence test showed
      that the LMWLs calculated from monthly data for Portoroz and Kozina are
      coincident, but the LMWLs calculated from daily precipitation events are not.
      This difference could be explained by the greater variance of the isotopic
      composition of daily precipitation in comparison to monthly composite samples and
      also to the influence of evaporation during events below<1 mm at Portoroz during
      the extremely dry and warm spring-summer season of 2003. Finally, synoptic maps
      and backward trajectories of a selected precipitation event showed that changes
      of isotopic composition are related to mixing of air masses originating from the
      continent and Mediterranean cyclogenesis.

PMID- 18041622
TI  - Estimating groundwater mixing and origin in an overexploited aquifer in
      Guanajuato, Mexico, using stable isotopes (strontium-87, carbon-13, deuterium and
      oxygen-18).
AB  - Stable Isotopes (strontium-87, deuterium and oxygen-18, carbon-13) have been used
      to reveal different sources of groundwater and mixing processes in the aquifer of
      the Silao-Romita Valley in the state of Guanajuato, Mexico. Calcite dissolution
      appeared to be the main process of strontium release leading to relatively equal
      (87)Sr/(86)Sr ratios of 0.7042-0.7062 throughout the study area which could be
      confirmed by samples of carbonate rocks having similar Sr ratios (0.7041-0.7073).
      delta(13)C values (-11.91- -6.87 per thousand VPDB) of groundwaters confirmed the
      solution of carbonates but indicated furthermore influences of soil-CO(2).
      Deuterium and (18)O contents showed a relatively narrow range of-80.1- -70.0 per
      thousand VSMOW and -10.2- -8.8 per thousand, VSMOW, respectively but are affected
      by evaporation and mixing processes. The use of delta(13)C together with
      (87)Sr/(86)Sr revealed three possible sources: (i) carbonate-controlled waters
      showing generally higher Sr-concentrations, (ii) fissure waters with low
      strontium contents and (iii) infiltrating water which is characterized by low
      delta(13)C and (87)Sr/(86)Sr ratios. The third component is affected by
      evaporation processes taking place before and during infiltration which might be
      increased by extraction and reinfiltration (irrigation return flow).

PMID- 18041623
TI  - Lead and strontium isotopes as indicators for mixing processes of waters in the
      former mine 'Himmelfahrt Fundgrube', Freiberg (Germany).
AB  - To pinpoint the origin and mixing processes of mine waters, different mine water
      types from the polymetallic sulphide ore deposit 'Himmelfahrt Fundgrube'
      (Freiberg, Germany) were analysed by thermal ionisation mass spectrometry using
      lead and strontium isotope ratios. Results show that the lead isotope composition
      of different mine waters results from a mixture of at least two sources: released
      lead from oxidised sulphide ores (mainly galena) and anthropogenic lead from
      groundwater. Furthermore, there are indications for an additional lead source.
      Strontium isotopes in mine waters identify at least three different sources:
      released strontium from weathered host rock (Grey Gneisses), released strontium
      from weathered gangue carbonates, and probably strontium from anthropogenic
      inputs. Contrary to former oxygen and sulphur isotope studies, strontium isotope
      compositions as well as hydrochemical parameters show the important role of
      gangue carbonates as an element source in mine waters.

PMID- 18041624
TI  - Isotopic characteristics of meteoric waters in the Belgrade region.
AB  - The stable isotope composition of hydrogen (delta(2)H) and oxygen (delta(18)O) in
      monthly precipitation and river water (Sava River and Danube) samples in the
      Belgrade area gathered between 1992 and 2005 are determined. The local meteoric
      water line delta(2)H=7.8 (+/-0.2) delta(18)O+7.3(+/-1.6) (r(2)=0.98, n=60,
      sigma=0.52) for the whole period of observation is close to the global meteoric
      water line. The amount-weighted mean delta(2)H and delta(18)O values of
      precipitation were-65+/-27 per thousand and-9.4+/-3.4 per thousand, respectively.
      Good correlation between delta(18)O values (r approximately >0.67) and ambient
      temperature and relative humidity was obtained. Stream-water data ranged from-94
      to-60 per thousand for delta(2)H and from-11.0 to approximately 5.7 per thousand
      for delta(18)O with highly statistically significant difference (p>0.01) between
      the Sava River and the Danube. In addition, the isotopic compositions of local
      precipitation and adjacent river water at monitoring sites were compared.
      Obtained data will give an opportunity to improve the knowledge of mixing stream
      water and local groundwater, and assessment of potential groundwater risks and
      pressures in the Belgrade basin.

PMID- 18041625
TI  - Characteristics of suspended matter in the River Sava watershed, Slovenia.
AB  - A combination of C/N ratios, delta(13)C and delta(15)N values in suspended matter
      was used to examine the seasonal (late summer 2004 and spring 2005) relationship
      with hydrological characteristics of the River Sava watershed in Slovenia. The
      values of C/N ratios range from 1.2 to 19.1, delta(13)C values range from-29.2 to
      23.0 per thousand and delta(15)N values from 0.5 to 16.7 per thousand and
      indicate that the samples are a mixture of two end members: modern soils and
      plant litter. A simple mixing model was used to indicate that soil organic carbon
      prevails over plant litter and contributes more than 50% of suspended material.
      The calculated annual particulate organic carbon flux is estimated as 5.2x10(10)
      g C/year, the annual particulate nitrogen flux 8.5x10(9) g N/year and the total
      suspended solid flux is estimated to be 1.3x10(12) g/year. Anthropogenic impact
      was detected only in a tributary stream of the River Sava, which is located in an
      agriculture-industrial area and is reflected in higher delta(15)N values in
      suspended matter and high nitrate concentrations in the late summer season.

PMID- 18041626
TI  - Using radon-222 for tracing groundwater discharge into an open-pit lignite mining
      lake--a case study.
AB  - Groundwater discharge into an open pit lignite mining lake was investigated using
      radon-222 as a naturally occurring environmental tracer. The chosen study site
      was a meromictic lake, i.e., a water body that is divided horizontally into two
      separate layers--the upper mixolimnion (with seasonal mixing) and the lower
      monimolimnion (without seasonal mixing). For the estimation of groundwater
      discharge rates into the lake, a simple box model including all radon sinks and
      sources related to each layer was applied. Two field investigations were
      performed. During the October campaign, the total groundwater discharge into the
      lake was found to be 18.9 and 0.7 m(3) d(-1) for the mixolimnion and
      monimolimnion, respectively. During the December campaign, the groundwater
      discharge into the mixolimnion was 15.0 m(3) d(-1), whereas no discharge at all
      was observed into the monimolimnion. Based on the given water volumes, the
      residence time of lake water was 5.3 years for the monimolimnion and varies
      between 0.9 and 1.1 years for the mixolimnion. The investigation confirmed radon
      to be a useful environmental tracer for groundwater and surface water
      interactions in meromictic lake environments.

PMID- 18041629
TI  - Self-reported knowledge and behaviors related to oral and dental health in
      Turkish children.
AB  - AIM: The purpose of the study was to present oral- and dental health-related
      knowledge and behaviors of children who presented to Akdeniz University Medical
      Faculty Pediatric Outpatient Clinic between March 1 and May 1, 2006 for non
      dental health reasons. METHOD: Data were collected from a total of 173 children.
      A survey which contained questions about the children's oral and dental health
      was completed using face-to-face interview technique. RESULTS: Forty-eight
      percent of the children were 5-6 years old and 68.8% were not going to school. It
      was determined that 43.3% of the mothers of the children in the study had a
      primary-school level of education and 74.6% were housewives. It also was
      determined that 49.1% of the children had never had a cavity, 43.4% stated that
      they brushed their teeth after meals, and 30.6% stated that they brushed at least
      once a day. More than sixty percent of the children spent their allowance on
      chocolate, chips, cola, candy, and other acidic drinks. A significant
      relationship was found between the children's ages and having a caries in this
      study. There also was a statistically significant relationship between the
      parents' tooth-brushing habit and the children's tooth brushing, and between the
      parents' frequency of tooth brushing and the children's frequency of tooth
      brushing. CONCLUSION: Based on the results of the study it is recommended that
      both children and their families be given education about oral and dental health.

PMID- 18041630
TI  - Adolescents born with spina bifida: experiential worlds and biopsychosocial
      developmental challenges.
AB  - The author used phenomenological (interpretive) ethnography to investigate the
      experience of physical disability and its attached meanings in relation to self,
      world, and other for adolescents born with spina bifida. Multiple in-depth
      interviews were conducted with 11 late-stage adolescents (aged 18-24 years).
      Analysis of their narrative accounts illustrated commonalities with respect to
      the biopsychosocial impact of living with the physical disability of spina
      bifida. The theme, "Experiencing self as dissimilar other" is reported upon.
      Findings imply that youth born with spina bifida face biological, psychological,
      and social challenges that might interfere with normative developmental tasks of
      adolescence, including identity formation. Greater emphasis needs to be directed
      toward humanizing and emancipating the physical and social environment for youth
      with physical disabilities to maximize developmental opportunities and potential
      while fostering positive identity.

PMID- 18041631
TI  - Evidence-based practice: a primer for action.
AB  - Although evidence-based practice (EBP) began as a challenge to the medical
      profession in the early 1970s, the concept has since been embraced by nursing and
      other health care professions. Although it is clear that the process of placing
      evidence into practice will continue to be refined, the mandate to do so is
      clear. The purpose of this article is to present a brief history of the
      definition of EBP, describe some of the more well-known models of knowledge
      translation, discuss some of the commonly agreed-upon steps in the EBP process,
      and present some resources that might be useful for readers.

PMID- 18041633
TI  - Design aspects of poly(alkylcyanoacrylate) nanoparticles for drug delivery.
AB  - Poly(alkylcyanoacrylate) (PACA) nanoparticles were first developed 25 years ago
      taking advantage of the in vivo degradation potential of the polymer and of its
      good acceptance by living tissues. Since then, various PACA nanoparticles were
      designed including nanospheres, oil-containing and water-containing nanocapsules.
      This made possible the in vivo delivery of many types of drugs including those
      presenting serious challenging delivery problems. PACA nanoparticles were proven
      to improve treatments of severe diseases like cancer, infections and metabolic
      disease. For instance, they can transport drugs across barriers allowing delivery
      of therapeutic doses in difficult tissues to reach including in the brain or in
      multidrug resistant cells. This review gives an update on the more recent
      developments and achievements on design aspects of PACA nanoparticles as delivery
      systems for various drugs to be administered in vivo by different routes of
      administration.

PMID- 18041634
TI  - Optimization of ultrasound and microbubbles targeted gene delivery to cultured
      primary endothelial cells.
AB  - Ultrasound and microbubbles targeted gene delivery (UMTGD) is a promising
      technique for local gene delivery. As the endothelium is a primary target for
      systemic UMTGD, this study aimed at establishing the optimal parameters of UMTGD
      to primary endothelial cells. For this, an in vitro ultrasound (US) setup was
      employed in which individual UMTGD parameters were systematically optimized. The
      criteria for the final optimized protocol were: (1) relative high reporter gene
      expression levels, restricted to the US exposed area and (2) induction of not
      more than 5% cell death. US frequency and timing of medium replacement had a
      strong effect on UMTGD efficiency. Furthermore, US intensity, DNA concentration
      and total duration of US all affected UMTGD efficiency. Optimal targeted gene
      delivery to primary endothelial cells can be accomplished with Sonovue
      microbubbles, using 20 microg/ml plasmid DNA, a 1 MHz US exposure of Ispta 0.10
      W/cm(2) for 30 s with immediate medium change after UMTGD. This optimized
      protocol resulted in both an increase in the number of transfected cells (more
      than three fold) and increased levels of transgene expression per cell (170%).

PMID- 18041635
TI  - Active tumor-targeted delivery of PEG-protein via transferrin-transferrin
      receptor system.
AB  - Transferrin (Tf) holds promise as a drug carrier because of overexpress
      transferring receptors (TfRs) on the surface of tumor cells. The purpose of this
      work was to conjugate Tf to PEGylated protein (Tf-PEG-protein) to improve tumor
      targeted delivery of PEG-protein. After a model protein, beta-lactoglobulin B
      (LG), was modified by the heterobifunctional polyethyleneglycol (PEG), Tf was
      covalently linked to the distal end of the PEG chains on the PEG-LG (PL)
      conjugate. The purified Tf-PEG-LG (TPL) contained 1.4 of Tf ligand on one LG
      molecule. The specificity and affinity of TPL to TfR on two kinds of tumor cells
      (K562 and KB cells) were assessed. The results demonstrated that, TPL can bind
      specifically to the TfR on the tumor cell surface and the affinity of the
      conjugate to TfR was similar to that of native Tf. The pharmacokinetics and
      biodistribution studies in rodents found that TPL exhibited a significantly
      delayed blood clearance, the longest tumor resident time and the greatest tumor
      accumulation, as compared with LG and PL. Such design of the Tf conjugate would
      suggest a promising approach for active tumor targeting of therapeutic proteins
      or peptides to target cells.

PMID- 18041636
TI  - Transfection of primary human nasal epithelial cells using a biodegradable poly
      (ester amine) based on polycaprolactone and polyethylenimine as a gene carrier.
AB  - The purpose of this study was to prepare and characterize poly (ester amine)
      (PEA)/pGL3 complexes and investigate their transfection efficiency in human nasal
      epithelial (HNE) cells. Particle size, zeta potential, and gel retardation
      characteristics of PEA /pGL3 complexes were also measured. After treatment of
      DNase-I, protection and release assay of PEA/pGL3 complexes were performed. To
      assess the transfection efficiency and cytotoxicity, measurement of relative
      luciferase activity and MTS assay were performed. PEA/pGL3 complexes showed
      effective and stable DNA condensation with the particle sizes below 200 nm,
      implicating their potential for intracellular delivery. PEA/pGL3 complexes
      successfully transfected into the HNE cells with higher viability of the cells.
      These results suggested that, the PEA can be used as an efficient cationic
      polymeric vehicle which provides a versatile platform for further investigation
      of structure property relationship along with the controlled degradation,
      significant low cytotoxicity, and high transfection efficiency of the primary HNE
      cells.

PMID- 18041637
TI  - Colon-specific drug delivery for mebeverine hydrochloride.
AB  - Mebeverine Hydrochloride (MB-HCl), an effective spasmolytic drug, was formulated
      as CODES. A colon-specific drug delivery technology CODES was designed to avoid
      the inherent problems associated with pH- or time-dependent systems. To achieve
      more protection and control of drug release, MB-HCl was prepared as microspheres
      and compressed as core tablets of CODES (modified CODES). The core tablets
      contained the drug either in free form [Formula 1 (F(1))], or as microspheres
      with 2 different polymer:drug:lactulose ratios (1:1:0.5 [Formula 2 (F(2))] and
      2:1:0.5 [Formula 3 (F(3))]. The release profiles of the coated CODES systems were
      compared with uncoated compressed tablets. The uncoated tablet showed a drug
      release of 94% after 1 h in simulated gastric condition (pH = 1.2). The release
      characteristics of the coated systems revealed that the enteric coating (Eudragit
      L(100)) prevented any drug release in simulated gastric or duodenal conditions in
      the first 3 h (pH 1.2-6.1), after which drug was slightly liberated in simulated
      intestinal fluid (pH 7.4) {Phase 1 (P1)}. After 4 h the pH was adjusted to 7 and
      beta-glucose-oxidase was added, which is an enzyme produced by enterobacteria
      present in the colon. The acid-soluble coat (Eudragit)E(100)) dissolved and the
      drug release suddenly increased to reach 95, 72 and 60.4% for F(1)-F(3),
      respectively. IR spectrum study showed a covalent bond between the drug and the
      polymer in the formulae F(2) and F(3) resulting in the sustained drug release
      from the microspheres with a significant difference (p>0.05) to F(1). The
      findings were confirmed by in vivo investigation using X-ray images for Guinea
      pigs ingested tablets containing barium sulphate (F(4)), where the tablet began
      to disintegrate after 10 h of tablet intake. The results of the study indicated
      that MB-HCl CODES colon-specific drug delivery can act as a successful trigger
      for drug targeting in the colon. Furthermore, a sustained release of the drug can
      be achieved from modified CODES containing the drug in the form of microspheres.

PMID- 18041638
TI  - M-cell targeted biodegradable PLGA nanoparticles for oral immunization against
      hepatitis B.
AB  - The transcytotic capability and expression of distinct carbohydrate receptors on
      the intestinal M-cells render it a potential portal for the targeted oral vaccine
      delivery. PLGA nanoparticles loaded with HBsAg were developed and antigen was
      stabilized by co-encapsulation of trehalose and Mg(OH)(2). Additionally, Ulex
      europaeus 1 (UEA-1) lectin was anchored to the nanoparticles to target them to M
      cells of the peye's patches. The developed systems was characterized for shape,
      size, polydispersity index and loading efficiency. Bovine submaxillary mucin
      (BSM) was used as a biological model for the in vitro determination of lectin
      activity and specificity. The targeting potential of the lectinized nanoparticles
      were determined by Confocal Laser Scanning Microscopy (CLSM) using dual staining
      technique. The immune stimulating potential was determined by measuring the anti
      HBsAg titre in the serum of Balb/c mice orally immunized with various lectinized
      formulations and immune response was compared with the alum-HBsAg given
      intramuscularly. Induction of the mucosal immunity was assessed by estimating
      secretary IgA (sIgA) level in the salivary, intestinal and vaginal secretion.
      Additionally, cytokines (interleukin-2; IL-2 and interferon-gamma; IFN-gamma)
      level in the spleen homogenates was also determined. The results suggest that
      HBsAg can be successfully stabilized by co-encapsulation of protein stabilizers.
      The lectinized nanoparticles have demonstrated approximately 4-fold increase in
      the degree of interaction with the BSM as compared to plain nanoparticles and
      sugar specificity of the lectinized nanoparticles was also maintained. CLSM
      showed that lectinized nanoparticles were predominantly associated to M-cells.
      The serum anti-HBsAg titre obtained after oral immunization with HBsAg loaded
      stabilized lectinized nanoparticles was comparable with the titre recorded after
      alum-HBsAg given intramuscularly. The stabilized UEA-1 coupled nanopartilces
      exhibited enhanced immune response as compared to stabilized non-lectinized
      nanoparticles. Furthermore, the stabilized lectinized nanoparticles elicited sIgA
      in the mucosal secretion and IL-2 and IFN-gamma in the spleen homogenates. These
      stabilized lectinized nanoparticles could be a promising carrier-adjuvant for the
      targeted oral-mucosal immunization.

PMID- 18041639
TI  - Polyethylenimine-DNA solid particles for gene delivery.
AB  - Polyethylenimine (PEI), a cationic polymer, was used to develop a non-viral
      vector for gene delivery. A simple, reproducible process is described with which
      to condense plasmid DNA with PEI. When prepared at the optimum charge ratio of
      6.3 ( +/- ; PEI:DNA, 5:1 w/w), PEI-DNA complexes were 30-60 nm in diameter and
      excluded intercalating dyes from the plasmid DNA. The particles were stable for
      more than one month at 4 degrees C with respect to size and transfection
      activity. PEI-condensed DNA transfected a broad range of murine and human tumor
      cell lines (B16, Lewis Lung, SK-OV-3 and LS180) in vitro in the presence of fetal
      calf serum. Intraperitoneal administration of PEI-condensed DNA resulted in
      significant gene expression in a human ovarian cancer peritoneal xenograft model.

PMID- 18041641
TI  - A cross-industry assessment of personal exposures to methyl methacrylate.
AB  - This study investigated personal exposures to methyl methacrylate (MMA) monomer
      during monomer production and use within the chemical manufacturing industry. The
      aim was to include multiple companies and sites to provide information regarding
      differences and similarities among exposure subgroups within the industry during
      the time period of 1998-2000. To this end, personal exposure data for MMA monomer
      from three chemical corporations was combined into a single data set. The data
      was stratified by sample type (full shift or short term), job classification
      (monomer production, monomer use, maintenance, distribution, and laboratory
      operations), company, and facility. Only classifications with three samples or
      more were included in the final data set, yielding 376 samples for analysis (334
      full-shift and 42 short-term samples). Results compare well with previously
      published data on MMA monomer exposures. Although there was significant
      variability in several exposure subgroups (particularly among companies and
      facilities), MMA monomer use in the manufacture of other products resulted in the
      highest exposure distributions, with lower exposures associated with monomer
      production, maintenance, and distribution operations. The usefulness of these
      findings is related to the provision of information for discussion of current
      needs in the industry regarding data sampling, exposure assessment, and standards
      development.

PMID- 18041642
TI  - Laboratory and field testing of sampling methods for inhalable and respirable
      dust.
AB  - The performance of four sampling devices for inhalable dust and three devices for
      respirable dust was tested with different kinds of dusts in the laboratory and in
      the field. The IOM sampler was chosen as the reference method for inhalable dust,
      and the IOM sampler provided with the porous plastic foam media was used as the
      reference method for respirable dust. The other tested instruments were the
      Button sampler, the optical Grimm aerosol monitor, and the Dekati two-stage
      cascade impactor with cutoff sizes of 10 and 4 mu m. The study confirmed the
      applicability of the IOM and Button samplers. The new foam product followed the
      respirable criteria well. However, the foam sampler was unstable for measuring
      inhalable dust, probably due to its moisture absorption. In addition, high dust
      loads should be avoided with the foam sampler due to increase in filtering
      efficiency. The concentrations of inhalable dust measured with the Button
      sampler, the Grimm monitor, and the impactor sampler were usually close to those
      measured with the reference sampler. On the other hand, impactor sampling yielded
      higher respirable dust concentrations than the reference method in the field,
      which may have been caused by particle bounce; high dust loads should be avoided
      while using the impactor. The results also showed that the Grimm monitor enables
      real-time dust concentration determinations that are accurate enough for routine
      monitoring of occupational exposure and for testing efficiency of control
      measures in workplaces.

PMID- 18041643
TI  - Issues when modeling benzene, toluene, and xylene exposures using a literature
      database.
AB  - A database of benzene, toluene, and xylene measurements was compiled from an
      extensive literature review that contained information on several exposure
      determinants, including job type, operation, mechanism of release, process type,
      ventilation, temperature, distance from the source, quantity, and location. The
      database was used to develop statistical models for benzene, toluene, and xylene
      exposure as a function of operation and other workplace determinants. These
      models can be used to predict exposure levels for subjects enrolled in community
      based case-control studies. This article presents the derived parameter estimates
      for specific operations and additional workplace exposure determinants and
      describes a number of statistical and data limitation issues that are inherent in
      determinants modeling of historical published data. [Supplementary materials are
      available for this article. Go to the publisher's online edition of Journal of
      Occupational and Environmental Hygiene for the following free supplemental
      resource(s): a PDF file of QQ plots and a Word file with references used in the
      benzene/toluene/xylene exposure database].

PMID- 18041644
TI  - Assessing total fungal concentrations on commercial passenger aircraft using
      mixed-effects modeling.
AB  - The primary objective of this study was to compare airborne fungal concentrations
      onboard commercial passenger aircraft at various in-flight times with
      concentrations measured inside and outside airport terminals. A secondary
      objective was to investigate the use of mixed-effects modeling of repeat measures
      from multiple sampling intervals and locations. Sequential triplicate culturable
      and total spore samples were collected on wide-body commercial passenger aircraft
      (n = 12) in the front and rear of coach class during six sampling intervals:
      boarding, midclimb, early cruise, midcruise, late cruise, and deplaning.
      Comparison samples were collected inside and outside airport terminals at the
      origin and destination cities. The MIXED procedure in SAS was used to model the
      mean and the covariance matrix of the natural log transformed fungal
      concentrations. Five covariance structures were tested to determine the
      appropriate models for analysis. Fixed effects considered included the sampling
      interval and, for samples obtained onboard the aircraft, location (front/rear of
      coach section), occupancy rate, and carbon dioxide concentrations. Overall, both
      total culturable and total spore fungal concentrations were low while the
      aircraft were in flight. No statistical difference was observed between
      measurements made in the front and rear sections of the coach cabin for either
      culturable or total spore concentrations. Both culturable and total spore
      concentrations were significantly higher outside the airport terminal compared
      with inside the airport terminal (p-value < 0.0001) and inside the aircraft (p
      value < 0.0001). On the aircraft, the majority of total fungal exposure occurred
      during the boarding and deplaning processes, when the aircraft utilized ancillary
      ventilation and passenger activity was at its peak.

PMID- 18041645
TI  - Effects of Hoods and Flame-Retardant Fabrics on WBGT Clothing Adjustment Factors.
AB  - Personal protective clothing (PPC) may include hoods and flame-retardant (FR)
      fabrics that may affect heat transfer and, thus, the critical wet bulb globe
      temperature (WBGT crit) to maintain thermal equilibrium. The purpose of this
      study was to compare the differences in WBGT crit for hooded vs. nonhooded
      versions of particle barrier and vapor barrier coveralls as well as for coveralls
      made of two flame-retardant fabrics (INDURA cotton and Nomex). Acclimated men (n
      = 11) and women (n = 4) walked on a treadmill in a climatic chamber at 180 W/m2
      wearing four different ensembles: limited-use, particle barrier coveralls with
      and without a hood (Tyvek 1427), and limited-use vapor barrier coveralls with and
      without a hood (Tychem QC, polyethylene-coated Tyvek). Twelve of the participants
      wore one of two flame-retardant coveralls. All participants wore standard cotton
      clothing. Progressive exposure testing at 50% relative humidity (rh) was designed
      so that each subject established a physiological steady-state followed by a clear
      loss of thermal equilibrium. WBGT crit was the WBGT 5 min prior to a loss of
      thermal equilibrium. Hooded ensembles had a lower WBGT crit than the nonhooded
      ensembles. The difference suggested a clothing adjustment of 1 degrees C for
      hoods. There were no significant differences among the FR ensembles and cotton
      work cloths, and the proposed clothing adjustment for FR coveralls clothing is 0
      degrees C.

PMID- 18041646
TI  - Testing antimicrobial paint efficacy on gypsum wallboard contaminated with
      Stachybotrys chartarum.
AB  - The goal of this research was to reduce occupant exposure to indoor mold through
      the efficacy testing of antimicrobial paints. An accepted method for handling
      Stachybotrys chartarum-contaminated gypsum wallboard (GWB) is removal and
      replacement. This practice is also recommended for water-damaged or mold
      contaminated GWB but is not always followed completely. The efficacy of
      antimicrobial paints to eliminate or control mold regrowth on surfaces can be
      tested easily on nonporous surfaces. The testing of antimicrobial efficacy on
      porous surfaces found in the indoor environment, such as gypsum wallboard, can be
      more complicated and prone to incorrect conclusions regarding residual organisms.
      The mold S. chartarum has been studied for toxin production and its occurrence in
      water-damaged buildings. Research to control its growth using seven different
      antimicrobial paints and two commonly used paints on contaminated, common gypsum
      wallboard was performed in laboratory testing at high relative humidity. The
      results indicate differences in antimicrobial efficacy for the period of testing,
      and that proper cleaning and resurfacing of GWB with an antimicrobial paint can
      be an option in those unique circumstances when removal may not be possible.

PMID- 18041647
TI  - Levels of Smad7 regulate Smad and mitogen activated kinases (MAPKs) signaling and
      controls erythroid and megakaryocytic differentiation of erythroleukemia cells.
AB  - Smad and MAPK signaling cascades are involved in erythroid and megakaryocytic
      differentiation. The inhibitory Smad for TGF-beta/activin signaling, Smad7, may
      directly or indirectly affect these signaling pathways. By modulating Smad7
      expression, we attempted to delineate the relevance of Smad7 during erythro
      megakaryocytic (E/M) differentiation of human erythroleukemia cells. Smad7
      transcripts were detected at low levels in different erythroleukemia cell lines
      (TF-1, HEL and K562). Reduction of expression of endogenous Smad7 by RNA
      interference enhanced erythroid differentiation of K562 cells in response to
      physiological doses of activin-A/TGF-beta1. Stable over-expression of Smad7 in
      K562 cells (K562/7) prevented activation of Smad2/3 and MAPK (ERK1/2, p38 and
      JNK1/2) proteins by activin-A/TGF-beta1 and subsequent induction of erythroid
      differentiation. High levels of Smad7 also interfered with hydroxyurea- and
      butyrate-, but not hemin-induced erythroid differentiation. Interestingly, K562/7
      cells were found to harbor a significant proportion (about 35%) of large ploy
      nucleated cells compared to fewer than 12% in control cells. K562/7 cells treated
      with phorbol 12-myristate 13-acetate (PMA), showed a great shift in ploidy
      towards high ploidy classes (> or =8N) accompanied with an increase in the
      expression of the maturation marker CD42b. We showed here that: (a) low levels of
      endogenous Smad7 in erythroleukemia cells are physiologically relevant, and (b)
      high levels of Smad7 interferes with TGF-beta/activin-induced Smad/MAPK signaling
      and erythro-differentiation and promotes megakaryocytic differentiation, possibly
      by blocking autocrine TGF-beta.

PMID- 18041648
TI  - Thrombopoietin is not uniquely responsible for thrombocytosis in inflammatory
      disorders.
AB  - A few studies in patients with reactive thrombocytosis identified levels of the
      hormone higher than expected, and suggested that TPO behaves as an acute-phase
      protein and was responsible for increased platelet count. At the opposite, other
      studies did not find any significant rise of the hormone in patients who
      similarly developed reactive thrombocytosis. To gain further information on this
      topic, we compared TPO levels and platelet counts in two series of patients
      hospitalized for acute illnesses: one with strong elevation of both erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP), and the other with normal
      values. Within the group of subjects with high ESR and CRP, 38 had normal
      platelet counts, while 15 had thrombocytosis. No thrombocytosis was observed in
      control patients. Patients with high acute phase indexes had significantly higher
      TPO levels and platelet counts than control patients. We identified significant
      positive correlations between ESR and CRP, and between TPO and CRP.
      Interestingly, no significant relationship between platelet counts and TPO levels
      was find. When we grouped patients with acute-phase reaction according to absence
      or presence of thrombocytosis, we found similar TPO values. Conversely, positive
      correlations between platelet count and IL-6 and between TPO and IL-6 have been
      identified. All together our results confirm that TPO acts as an acute phase
      protein but exclude the possibility that it is uniquely responsible for
      thrombocytosis of inflammatory disorders, which might recognize in IL-6 a
      credible candidate as a cooperating factor.

PMID- 18041649
TI  - Serotonin modulates the oxidative burst of human phagocytes via various
      mechanisms.
AB  - Serotonin, the major secretory product of activated platelets, has been widely
      reported as regulating various constituents of the immune system and immune
      functions. This modulation is complex and the data available are rather
      controversial. The aim of the present study was to clarify the mechanisms of
      serotonin action on human phagocytes. The effect of serotonin in a concentration
      range of 10(-7) M-10(-3) M on various parameters of oxidative burst of phagocytes
      was studied using various luminol-enhanced chemiluminescence methods. Serotonin
      inhibited the chemiluminescence response of the cells in a dose dependent manner.
      The effect of serotonin on the activity of myeloperoxidase was studied in further
      experiments. In this case, serotonin again exerted a dose dependent inhibition of
      the myeloperoxidase activity. The hypothesis that the inhibitory activity of
      serotonin might be also receptor mediated was evaluated using various serotonin
      receptor agonists and antagonists. None of the agonists studied exerted any
      direct antioxidative properties. Only (+/-)-DOI hydrochloride, a selective 5
      HTR(2) agonist, exerted similar effects on phagocytic cells as serotonin. It can
      be concluded that serotonin could affect the oxidative burst of phagocytes.
      Responsibility for its inhibitory effects lies with both the decrease in the
      generation of reactive oxygen species (due to the inhibition of myeloperoxidase
      activity) and with direct scavenging of reactive oxygen species. The effect of
      serotonin on phagocytes is also partially mediated by 5-HTR(2) receptor.

PMID- 18041650
TI  - Platelet activation in subjects with impaired glucose tolerance.
AB  - Impaired glucose tolerance (IGT), a prediabetic state, is associated with an
      increased risk of cardiovascular disease. Mean platelet volume (MPV), a
      determinant of platelet activation, is a newly emerging risk factor for
      atherothrombosis. This study was designed to answer the following questions: (i)
      Do MPV levels change in IGT? (ii) Is there any relation between MPV levels and 2
      h plasma glucose levels after 75 g oral glucose tolerance test. We selected 48
      subjects with IGT, and 48 healthy subjects with normal glucose tolerance matched
      for age, gender, and body mass index. MPV was significantly higher in IGT group
      than in control group (9.06 +/- 1.5 fl vs. 8.28 +/- 0.8 fl, p = 0.002). Also, MPV
      was positively correlated with 2 h plasma glucose concentration in IGT group (r =
      0.39, p = 0.006). In conclusion, our results suggest that subjects with IGT tend
      to have increased platelet activation. Increased platelet activity could
      contribute to increasing the risk of cardiovascular disease in IGT.

PMID- 18041651
TI  - Anti-platelet antibodies in a natural animal model of sulphonamide-associated
      thrombocytopaenia.
AB  - Delayed hypersensitivity (HS) reactions to sulphonamide antimicrobials occur in
      both humans and dogs with a similar clinical presentation, and may include
      thrombocytopaenia. Drug-dependent anti-platelet antibodies have been identified
      in humans with sulphonamide-associated thrombocytopaenia. Our purpose was to
      determine whether similar antibodies were present in dogs with sulphonamide
      associated thrombocytopaenia. Flow cytometry was used to detect anti-platelet
      antibodies in sera from 32 dogs with sulphonamide HS, eight dogs that tolerated
      sulphonamide therapy without adverse reactions and nine healthy control dogs were
      used as controls. Anti-platelet antibodies were found more frequently, with
      significantly stronger fluorescence signals, in HS dogs (75%) compared to
      'tolerant' dogs (38%), and in HS dogs with thrombocytopaenia (90%) compared to HS
      dogs with normal platelet counts (46%). Binding to platelets was enhanced in the
      presence of soluble sulphonamide in 42% of positive samples. Experiments with
      canine Glanzmann's platelets, and competition assays with fibrinogen fragments or
      anti-GP antibodies, did not support the hypothesis that these canine antibodies
      target the fibrinogen receptor. In conclusion, anti-platelet antibodies were
      identified in dogs with sulphonamide-associated thrombocytopaenia, which suggests
      a similar immunopathogenesis for this reaction in dogs as seen in humans. Further
      work in both species will determine whether these antibodies are pathogenic in
      vitro.

PMID- 18041652
TI  - Thrombocytopenia in patients with dengue virus infection in the Brazilian Amazon.
AB  - Thrombocytopenia may be occasionally observed in dengue fever (DF) but is a
      constant feature and one of the diagnostic criteria of dengue hemorrhagic fever
      (DHF). Its clinical presentation and relevance is still poorly described in the
      literature. Patients with fever and bleeding were referred to a tertiary care
      center in Manaus, in the Western Brazilian Amazon during the outbreak of dengue
      in 2001. They were hospitalized for clinical observation and supportive care.
      Platelet counts were performed on admission and throughout the hospitalization.
      Only patients with a serological confirmation or viral isolation of the dengue
      virus were included. One hundred and seventy eight patients were enrolled in the
      study (118 with DF and 60 with DHF). There was no association between the
      presence of active bleeding and the degree of thrombocytopenia on admission (P =
      0.302). A positive tourniquet test, hematemesis and ecchymoses were more frequent
      in DHF patients (P < 0.05). Patients with DHF had lower platelet counts than
      patients with DF (P < 0.001). There was a positive correlation between platelet
      counts and plasma albumin levels (r = 0.217; P = 0.016) and a negative
      correlation with ALT values (r = -0.3; P = 0.001). Clinical manifestations of
      thrombocytopenia are not related only to the number of peripheral platelets in
      dengue infection, but its recovery is associated with clinical improvement. The
      level of platelets correlates with the vascular leakage of proteins and liver
      damage.

PMID- 18041653
TI  - Reactive oxygen species and human platelet GP IIb/IIIa receptor activation.
AB  - This study concerned reactive oxygen species for their potential to activate
      human platelet GP IIb/IIIa receptors. All cells produce reactive oxygen species -
      radicals that can abstract electrons and hydrogen atoms from biological molecules
      to alter cell function. In many cells, radicals contribute to cellular signaling.
      In platelets, the predominant oxidant effect is platelet activation. Less is
      known concerning oxidants and GP IIb/IIIa receptor activation. The first aim of
      the current study was to confirm that although both H(2)O(2) and tert butyl
      hydroperoxide both predispose platelets to aggregation; neither directly
      activates GP IIb/IIIa receptors. The second aim was to demonstrate that even in
      the presence of extracellular redox iron; H(2)O(2) does not activate GP IIb/IIIa
      receptors. The third aim was to determine if extracellular superoxide anions
      evoke GP IIb/IIIa activation. Finally, a role for intra-platelet iron in GP
      IIb/IIIa activation was examined. Intracellular superoxide anions are produced in
      excess during platelet activation and curiously, they are uniquely able to
      increase intracellular free iron. This iron can, in a redox manner, generate
      radicals and these iron dependent species modulate signaling systems, including
      systems associated with adhesion receptor activation. In the current studies,
      platelets in suspension were exposed to H(2)O(2) and to tert butyl hydroperoxide,
      to H(2)O(2) plus ferrous or ferric chloride (+/- ascorbate to enhance iron redox
      cycling) and to xanthine plus xanthine oxidase to generate extra-platelet
      superoxide anions. Intra-platelet iron was increased with iron ionophore 8
      hydroxyquinoline. During flow cytometry, intra-platelet oxidant state was
      assessed with the redox sensitive fluorescent indicator H2DCF, while GP IIb/IIIa
      activation was assessed using fluorescent antibody PAC-1. Results showed that
      although all the oxidizing systems examined increased intra-platelet oxidant
      state, GP IIb/IIIa receptors were not activated by H(2)O(2), by tert butyl
      hydroperoxide, by H(2)O(2) plus iron (+/- ascorbate) or by xanthine plus xanthine
      oxidase. In contrast, iron plus ionophore 8-hydroxyquinoline evoked GP IIb/IIIa
      activation. Platelet positivity for PAC-1 increased from 2 +/- 0.2 to 28 +/- 7%
      (P < 0.005). However this response, although vigorous, was less than 56 +/- 8% (P
      < 0.001) evoked by thrombin 0.1 milliunit/ml. In conclusion, the results
      indicated that oxidant systems external to platelets did not activate GP IIb/IIIa
      receptors while increased intra-platelet iron was associated with appearance of
      cytosolic oxidizing species and with GP IIb/IIIa receptor activation.

PMID- 18041654
TI  - Platelet pathology in carriers of the X-linked GATA-1 macrothrombocytopenia.
AB  - Previous investigations from our laboratory have characterized the
      ultrastructural and cytochemical pathology of platelets in male members of a
      family with X-linked GATA-1 G208S macrothrombocytoenia. A large proportion of
      their circulating platelets were hypogranular macrothrombocytes, resembling cells
      from patients with the Gray Platelet Syndrome. However, most of the GATA-1
      macrothrombocytes contained some alpha granules, and a small number had as many
      as are present in normal platelets. GATA-1 macrothrombocytes also contained
      tubular inclusions formed from elements of the dense tubular system wrapped
      around each other like scrolls. Many macrothrombocytes contained flat tubular
      membrane sheets connected to channels of the open canalicular system, platelets
      in platelets and platelets attached to platelets forming very large
      macrothrombocytes. The present study has examined one obligate and three
      potential female carriers in this family. Thin sections of their platelets
      examined in the electron microscope revealed features consistent with the
      pathology observed in male family members. Most of their platelets were normal
      sized, discoid cells containing the usual complement of alpha and delta storage
      organelles and channels of the dense tubular system and OCS. However, a
      significant number of giant platelets containing the usual frequency of alpha and
      delta granules and hypogranular and agranular giant platelets were observed. The
      frequency of the macrothrombocytes varied in each of the four women studied, but
      were present in all. The ability of their platelets to bind multimers of vWF, in
      contrast to male family members, did not differ from normal controls. Near normal
      as well as normal platelet counts and the ability of their platelets to bind vWF
      multimers may protect them from the serious bleeding problems of males with the X
      linked GATA-1 G208S mutation. Our findings indicate that obligate female carriers
      of the GATA-1 gene can be detected by examination of their platelets in the
      electron microscope and distinguished from the pathology of other giant platelet
      disorders.

PMID- 18041655
TI  - Children and adolescents presenting in general practice: potential for
      identification and intervention against overweight.

PMID- 18041657
TI  - Factors influencing GPs' choice between drugs in a therapeutic drug group. A
      qualitative study.
AB  - OBJECTIVE: To explore how GPs choose between drugs in a therapeutic drug group.
      DESIGN: A qualitative study based on semi-structured ethnographic interviews.
      SETTING AND SUBJECTS: General practitioners from the counties of both Funen and
      West Zealand in Denmark. A total of 15 general practitioners (GPs) were selected
      with reference to variation in organizational structure, age, and gender. MAIN
      OUTCOME MEASURES: GPs' description of drug choice in relation to specific patient
      encounters involving a prescription. RESULTS: All informants appeared to consider
      drug price important as it was a recurring theme during all interviews. External
      factors outside the GP's control such as governmental regulation on prescribing
      and the pharmaceutical industry influenced most GPs. Internal factors related to
      the actual consultation included characteristics of the GP and the patient, drug
      characteristics, and repeat prescriptions. These factors interact in a non-linear
      and unpredictable way similar to complex adaptive systems. CONCLUSION: GPs
      balance both internal and external factors when choosing between analogues. Drug
      choice is a regulated process in the realm of complex prescribing behaviour with
      drug costs as a major factor.

PMID- 18041658
TI  - The lesser evil? Initiating a benzodiazepine prescription in general practice: a
      qualitative study on GPs' perspectives.
AB  - OBJECTIVE: Chronic benzodiazepine (BZD) use is widespread and linked with adverse
      effects. There is consensus concerning the importance of initiating BZD as a
      crucial moment. Nevertheless specific research in this field is lacking. This
      paper addresses the views of GPs on why they start prescribing BZDs to first-time
      users. DESIGN: Qualitative study with five focus groups analysed using a
      systematic content analysis. SETTING: Regions of Ghent and Brussels in Belgium.
      SUBJECTS: A total of 35 general practitioners. MAIN OUTCOME MEASURE: The GPs'
      perspective on their initiating of BZD prescribing. RESULTS: GPs reported that
      they are cautious in initiating BZD usage. At the same time, GPs feel overwhelmed
      by the psychosocial problems of their patients. They show empathy by prescribing.
      They feel in certain situations there are no other solutions and they experience
      BZDs as the lesser evil. They admit to resorting to BZDs because of time
      restraint and lack of alternatives. GPs do not perceive the addictive nature of
      BZD consumption as a problem with first-time users. GPs do not specifically
      mention patients' demand as an element for starting. CONCLUSION: The main concern
      of GPs is to help the patient. GPs should be aware of the addictive nature of BZD
      even in low doses and a non-pharmacological approach should be seen as the best
      first approach. If GPs decide to prescribe a BZD they should make plain to the
      patient that the medication is only a "temporary" solution with clear agreements
      with regard to medication withdrawal.

PMID- 18041659
TI  - Interdisciplinary cooperation of GPs in palliative care at home: a nationwide
      survey in The Netherlands.
AB  - OBJECTIVE: To investigate the occurrence and predictors of interdisciplinary
      cooperation of GPs with other caregivers in palliative care at home. DESIGN: In a
      prospective study among 96 general practices, the GPs involved identified all
      dying patients during the study period of 12 months. The GPs received an
      additional post-mortem questionnaire for each patient who died during the study
      period, and registered the healthcare providers with whom they cooperated.
      Multivariable logistic regression analysis was used to identify the predictors of
      GP cooperation with other caregivers. SETTING: Second Dutch National Survey in
      General Practice. SUBJECTS: A total of 743 patients who received palliative care
      according to their GP. MAIN OUTCOME MEASURES: Interdisciplinary cooperation
      between GP and other healthcare providers. RESULTS: During the study period, 2194
      patients died. GPs returned 1771 (73%) of the questionnaires. According to the
      GPs, 743 (46%) of their patients received palliative care. In 98% of these
      palliative care patients, the GP cooperated with at least one other caregiver,
      with a mean number of four. Cooperation with informal caregivers (83%) was most
      prevalent, followed by cooperation with other GPs (71%) and district nurses
      (63%). The best predictors of cooperation between GPs and other caregivers were
      the patient's age, the underlying disease, and the importance of psychosocial
      care. CONCLUSION: In palliative care patients, GP interdisciplinary cooperation
      with other caregivers is highly prevalent, especially with informal caregivers
      and other primary care collaborators. Cooperation is most prevalent in younger
      patients, patients with cancer as underlying disease, and if psychosocial care is
      important.

PMID- 18041660
TI  - The fibromyalgia diagnosis: hardly helpful for the patients? A qualitative focus
      group study.
AB  - OBJECTIVE: To explore experiences and consequences of the process of being
      diagnosed with fibromyalgia. DESIGN: Qualitative focus-group study. SETTING: Two
      local self-help groups. SUBJECTS: Eleven women diagnosed with fibromyalgia. MAIN
      OUTCOME MEASURES: Descriptions of experiences and consequences of the process of
      being diagnosed with fibromyalgia. RESULTS: Many participants had been suffering
      for years, and initial response of relief was common. For some, the diagnosis
      legitimized the symptoms as a disease, for others it felt better to suffer from
      fibromyalgia rather than more serious conditions. Nevertheless sadness and
      despair emerged when they discovered limitations in treatment options, respect,
      and understanding. Some patients keep the diagnosis to themselves since people
      seem to pay no attention to the name, or blatantly regard them as too cheerful or
      healthy looking. The initial blessing of the fibromyalgia diagnosis seems to be
      limited in the long run. The process of adapting to this diagnosis can be lonely
      and strenuous. CONCLUSION: A diagnosis may be significant when it provides the
      road to relief or legitimizes the patient's problems. The social and medical
      meaning of the fibromyalgia diagnosis appears to be more complex. Our findings
      propose that the diagnosis was hardly helpful for these patients.

PMID- 18041661
TI  - Clinical symptoms of cerebellar disease and their interpretation.

PMID- 18041663
TI  - Genetic profiling and tailored therapy in asthma: are we there yet?
AB  - Asthma is characterized by reversible bronchial hyper-responsiveness and airway
      inflammation, and encompasses a wide variety of patients with different clinical
      phenotypes that display variable responses to therapy. The definition of genomic
      variation presented in the Human Genome Project has facilitated the development
      of genetic-guided therapy in various diseases, including asthma. Tailored therapy
      is a reality in many types of malignancies where specific gene mutations or
      molecular profiles are identified and used to make critical therapeutic
      decisions. Despite the identification of beta-adrenergic receptor polymorphisms
      by Liggett and colleagues during the 1990s, the pharmacogenetics of asthma is
      still in its infancy. There have been great advances in asthma pharmacogenetics
      and pharmacotherapy with the completion of several large trials highlighting the
      effects of genotype on response to asthma therapy. This review focuses on
      research articles that serve to emphasize the potential role of using genotyping
      as a tool to develop individualized patient treatment regimens for asthma, thus
      improving outcomes and limiting adverse effects of certain therapies.

PMID- 18041664
TI  - Smoking behavior and related cancers: the role of CYP2A6 polymorphisms.
AB  - Smoking exerts complex central and peripheral nervous system, behavioral,
      cardiovascular, and endocrine effects in humans and is a primary risk factor for
      various cancers. Nicotine, a major constituent of tobacco, is the compound that
      is responsible for the development and maintenance of tobacco dependence. The
      absorbed nicotine is rapidly and extensively metabolized to inactive cotinine by
      CYP2A6 in human livers, which has a major impact on nicotine clearance. Progress
      has been made in understanding the relationship between the inter-individual
      variability in nicotine metabolism and genetic polymorphisms of CYP2A6. Recent
      findings have increased our knowledge concerning ethnic differences in the allele
      frequencies of the CYP2A6 variants, nicotine metabolism, and cancer risk. In this
      review, the potential associations between the CYP2A6 polymorphisms and smoking
      behavior or the risk of cancer are also discussed.

PMID- 18041665
TI  - The genetic determinants of atorvastatin response.
AB  - The statins or HMG-CoA reductase inhibitors are considered one of the most
      effective classes of drugs for reducing LDL and total cholesterol. Although,
      statin treatment has beneficial effects in the prevention of cardiovascular
      disease, considerable inter-individual variation exists in response to statin
      therapy, as well as in the incidence of adverse effects. Genetic factors
      contribute to patients' inter-variability in the lipid-lowering response to
      statins,drug-interactions and the occurrence of muscle damage havebeen reported.
      However, studies investigating aspects of pharmacokinetics, pharmacodynamics and
      disease-related genes have found no association that could impact on the
      decisions to treat with statins. Improved strategies that assess the simultaneous
      influence of multiple relevant susceptibility factors on disease risk (eg, diet,
      lifestyle and gene effects) are required. Data from pharmacogenetics studies
      investigating the association between gene variation and drug response and/or
      susceptibility to adverse effects are promising and are expected to impact on the
      clinical treatment of hypercholesterolemia.

PMID- 18041666
TI  - Electrotransfer of therapeutic molecules into tissues.
AB  - Electroporation is a physical method for the delivery of various molecules into
      cells by application of controlled external electrical fields that transiently
      increase permeability of the cell membrane. This technique is now widely used as
      an alternative to viral gene delivery for transfection of therapeutic genes into
      different tissues. Gene electrotransfer holds great potential for clinical
      application due to the ease of preparation of large quantities of endotoxin-free
      plasmid DNA, the control and reproducibility of this method, and the development
      of electric pulse generators approved for clinical use. Electroporation has been
      utilized mainly for DNA vaccination against infectious diseases and cancer. It
      has also been used for the delivery of other therapeutic genes, mainly cytokines,
      used in the treatment of various diseases, including cancer, arthritis, multiple
      sclerosis and inflammation, following organ transplantation. Electroporation as a
      delivery system for chemotherapeutic drugs, termed antitumor electrochemotherapy,
      is already at the clinical stage and is being used routinely in several oncology
      centers in Europe. In addition, the first clinical trials for electrogene therapy
      of cancer are ongoing. Therefore, it can be presumed that electrotransfer of
      therapeutic genes into tissues will soon form a validated alternative to viral
      delivery systems in a clinical setting.

PMID- 18041667
TI  - Cancer biomarkers: current issues and future directions.
AB  - Cancer biomarkers and characteristics of an ideal biomarker for cancer are
      discussed in this review, as well as technologies for their detection. The focus
      of this article is on the use of biomarkers for anticancer drug development and
      clinical applications, including determination of prognosis as well as monitoring
      of response to therapy. Types of biomarkers include methylated DNA sequences,
      mitochondrial DNA and microRNA. Within clinical research, oncology is expected to
      have the largest gains from biomarkers over the next five to ten years.
      Development of personalized medicine for cancer is closely linked to biomarkers,
      which may serve as the basis for diagnosis, drug discovery and monitoring of
      diseases. A major challenge in development of cancer biomarkers will be the
      integration of proteomics with genomics and metabolomics data and their
      functional interpretation in conjunction with clinical data and epidemiology.

PMID- 18041668
TI  - NMR-based metabolomics: translational application and treatment of cancer.
AB  - Cancer cells possess a highly unique metabolic phenotype which is characterized
      by high glucose uptake, increased glycolytic activity, decreased mitochondrial
      activity, low bioenergetic expenditure and increased phospholipid turnover. In
      addition to these general metabolic markers of malignancy, tissue-specific
      biochemistry has identified specific endogenous metabolites found in particular
      tumors types. These include N-acetyl aspartate in neuroblastoma, myo-inositol in
      gliomas and citrate in prostate cancer. Metabolic profiles can be readily
      assessed to monitor responsiveness and the development of resistance to novel
      targeted drugs, for example, where a cytostatic effect rather than cytotoxicity
      occurs. Using modern analytical technologies in combination with statistical
      approaches, a methodology termed 'metabolomics' has been developed. Metabolomics
      has been used to generate a global metabolic profile on patient samples, which
      can then be used to determine treatment response. This review describes existing
      NMR-based approaches for global metabolic profiling in tissue biopsies and body
      fluids and the use of non-invasive radiological techniques to assess metabolic
      biomarkers. In addition, studies on metabolic responses to novel targeted drugs,
      including tyrosine kinase inhibitors and metabolic modulators, are evaluated.

PMID- 18041669
TI  - An update on lipidomics: progress and application in biomarker and drug
      development.
AB  - Substantial progress has been made in the application of lipidomics in biomarker
      discovery and drug development, as well as in a variety of other areas. In
      particular, the number of published studies reporting the quantitation and
      analysis of low-abundance lipid molecular species has greatly increased. It can
      be anticipated that many of the biochemical mechanisms underlying metabolic
      syndromes and other lipid-related diseases will be identified through these
      methods. Importantly, lipid markers diagnostic of the onset, progression, or
      severity of these diseases as well as evaluation of drug efficacy and safety will
      be discovered as the ability to detect low-abundance lipid molecular species
      improves. An update of technical developments within the field of lipidomics from
      2006 to the present is provided, along with a brief discussion of its
      applications in biomarker and drug development.

PMID- 18041670
TI  - Ranibizumab, a mAb against VEGF-A for the potential treatment of age-related
      macular degeneration and other ocular complications.
AB  - Genentech Inc and Novartis Ophthalmics AG have developed and launched the
      humanized anti-VEGF antibody fragment ranibizumab, a 48-kDa humanized antibody
      fragment that inhibits all forms of biologically active VEGF-A, for the treatment
      of age-related macular degeneration by intravitreal administration. Phase I to
      III clinical trials to confirm the role of ranibizumab in the treatment of
      choroidal neovascularization (phase II and III), diabetic macular edema (phase II
      and III), retinal venous occlusion (phase II and III), telangiectasia (phase I
      and II), central serous chorioretinopathy (phase I), polypoidal choroidal
      vasculopathy (phase I/II), conjunctival neoplasms (phase I) and von Hippel-Lindau
      syndrome (phase I) are ongoing.

PMID- 18041671
TI  - MM-093, a recombinant human alpha-fetoprotein for the potential treatment of
      rheumatoid arthritis and other autoimmune diseases.
AB  - Merrimack Pharmaceuticals Inc (previously Atlantic Biopharmaceuticals) is
      developing MM-093 (formerly ABI-001), an injectable formulation of a recombinant
      human alpha-fetoprotein, for the potential treatment of myasthenia gravis,
      multiple sclerosis, rheumatoid arthritis, autoimmune uveitis and psoriasis. MM
      093 is currently undergoing phase II clinical trials for rheumatoid arthritis,
      psoriasis and autoimmune uveitis.

PMID- 18041673
TI  - AACR-NCI-EORTC--19th symposium. Molecular Targets and Cancer Therapeutics--Part
      1.

PMID- 18041674
TI  - AACR-NCI-EORTC--19th symposium. Molecular Targets and Cancer Therapeutics--Part
      2.

PMID- 18041675
TI  - AACR-NCI-EORTC--19th symposium. Molecular Targets and Cancer Therapeutics--Part
      3.

PMID- 18041676
TI  - AACR-NCI-EORTC--19th symposium. Molecular Targets and Cancer Therapeutics--Part
      4.

PMID- 18041677
TI  - Discovery on Target 2007--CHI's Fifth Annual Conference. RNAi for Drug Discovery
      and Therapeutics.

PMID- 18041678
TI  - Discovery on Target 2007--CHI's Fifth Annual Conference. Ion channels.

PMID- 18041679
TI  - BioPartnering Europe--15th Annual Conference. Highlights from open house and
      emerging company presentations--Part 1.

PMID- 18041680
TI  - BioPartnering Europe--15th Annual Conference. Highlights from open house and
      emerging company presentations--Part 2.

PMID- 18041681
TI  - Perspectives in interpandemic influenza.

PMID- 18041682
TI  - World Institute of Pain (WIP)--Fourth World Congress.

PMID- 18041683
TI  - Virtual Discovery Europe--Select Biosciences Conference. Computer-aided drug
      design and screening.

PMID- 18041684
TI  - International Clinical Trials Symposium 2007: improving healthcare in the new
      millennium.

PMID- 18041686
TI  - The impact of generic antiviral drugs.
AB  - The HIV/AIDS epidemic has spread worldwide, with approximately 40 million people
      who were infected by the end of 2006. Antiretroviral therapy (ART) has proven to
      be lifesaving, and can convert AIDS into a chronic but manageable disease. Until
      a few years ago, the annual cost of treating one patient with HIV/AIDS was
      between US $10,000 and $12,000--beyond the affordability of most individuals. In
      2001, the offer of a triple generic therapy at a cost of less than US $1 per day
      from the Indian company Cipla stunned the world. Although there were some initial
      challenges, this approach to HIV/AIDS treatment galvanized a reaction that had
      never occurred previously. Governments, the WHO, NGOs and other bodies quickly
      attempted to make ART available in the developing world. By 2006, almost 1.3
      million patients were receiving ART (comprising mostly generic drugs), a 5-fold
      increase compared with five years earlier; however, significant challenges in ART
      availability remain. With international patent laws now being applicable in India
      (and in most developing countries), generics companies may no longer be able to
      provide HIV/AIDS-afflicted countries with new third-generation drugs at low
      prices. Innovative solutions will need to be obtained urgently to address this
      issue.

PMID- 18041685
TI  - Targeting parasite-mediated host hemoglobin degradation in malaria.
AB  - Malaria is a major infectious disease in the tropics, with more than 300 million
      clinical cases reported annually. A vaccine for malaria does not exist, making
      the use of drugs for disease prophylaxis and treatment the only option available.
      The malaria parasite Plasmodium resides primarily within the host erythrocyte,
      where it exploits host cell components to meet its needs for life-cycle
      development. One of the most predominant and parasite-specific processes that
      occurs during this development is a rapid and organized degradation of the
      hemoglobin content of infected cells. Given that this parasite-mediated
      catabolization is critical for the growth of Plasmodium within the host cell, the
      degradation of hemoglobin has become one of the most well-established targets for
      antimalarial drug discovery.

PMID- 18041687
TI  - Pasireotide--a somatostatin analog for the potential treatment of acromegaly,
      neuroendocrine tumors and Cushing's disease.
AB  - Pasireotide (SOM-230) is a small somatostatin (SST) analog that is being
      developed by Novartis Pharma AG for the potential treatment of acromegaly,
      Cushing's disease and neuroendocrine tumors; the compound is currently in phase
      III clinical trials for Cushing's disease. Pasireotide exhibits high binding
      affinity to four of the five human (h)SST receptor subtypes, with IC50 values for
      hSST5 > hSST2 > hSST3 > hSST1; the compound displays no affinity for hSST4. The
      affinity profile of pasireotide resembles the profile of endogenous SSTs--a
      feature that is favorable given that different tumors exhibit differing SST
      receptor expression profiles. Pasireotide also exhibits a longer half-life than
      the clinically available SST analogs octreotide or lanreotide. Thus, this
      compound may be a better therapeutic agent than other analogs. In phase II
      clinical trials, pasireotide inhibited growth hormone (GH) secretion from GH
      secreting pituitary tumors, controlled symptoms associated with metastatic
      carcinoid tumors, and inhibited adrenocorticotropic hormone secretion in
      Cushing's disease. However, a major advantage for pasireotide compared with
      octreotide was not demonstrated. Commonly encountered side effects for the
      compound included mild to moderate gastrointestinal events (diarrhea, abdominal
      discomfort, nausea and vomiting). The efficacy of pasireotide and any potential
      advantage over current therapies will need to be tested or validated in larger
      phase III clinical trials.

PMID- 18041691
TI  - [Passive smoking--health consequences and effects of exposure prevention].
AB  - Passive smoking is the third leading but preventable cause of death worldwide. It
      is associated with an elevated risk of developing acute respiratory diseases,
      obstructive lung disorders, lung cancer, and cardiovascular disease. Whereas the
      dose-response relationship between second-hand smoke exposure and respiratory
      diseases is likely to be linear, a non-linear dose-response curve has been
      observed with respect to acute cardiovascular events. This explains the
      disproportionately high risk of myocardial infarction among passive smokers as
      compared to unexposed individuals. Over the last ten years, exposure to second
      hand smoke has declined in Germany, but it is still substantial. With passive
      smoking in the home being a difficult target for preventive measures, public
      smoking bans have recently been shown to greatly reduce second-hand smoke-related
      morbidity and mortality. In addition, such measures are usually well tolerated
      and highly relevant regarding legal aspects related to workplace issues. This
      article summarises the current evidence on the health consequences of passive
      smoking and on the favourable effects of public smoking bans.

PMID- 18041693
TI  - [Which integrative and disorder specific treatment approaches are considered in
      research papers? An analysis on psychotherapeutic treatments in German journals].
AB  - In the current discussion on optimizing psychotherapeutic approaches, two
      important developments have to be considered: a tendency towards integrative and
      a tendency towards disorder specific approaches. For the years 2005 and 2006, an
      analysis of three German journals (covering the fields of psychosomatics,
      psychiatry and clinical psychology) was conducted on the question whether these
      two developments can be identified in current empirical and conceptual
      publications. Contrary to the expectations, there are only very few papers
      dealing with integrative approaches. As expected, there is a major emphasis on
      psychodynamic and cognitive behavioural approaches; other approaches are only
      marginally considered. A disorder specific approach can be identified not only
      for cognitive behavioural, but also for psychodynamic papers.

PMID- 18041694
TI  - [Statistics for statistics?--Thoughts about psychological tools].
AB  - Statistical methods take a prominent place among psychologists' educational
      programs. Being known as difficult to understand and heavy to learn, students
      fear of these contents. Those, who do not aspire after a research carrier at the
      university, will forget the drilled contents fast. Furthermore, because it does
      not apply for the work with patients and other target groups at a first glance,
      the methodological education as a whole was often questioned. For many
      psychological practitioners the statistical education makes only sense by
      enforcing respect against other professions, namely physicians. For the own
      business, statistics is rarely taken seriously as a professional tool. The reason
      seems to be clear: Statistics treats numbers, while psychotherapy treats
      subjects. So, does statistics ends in itself? With this article, we try to answer
      the question, if and how statistical methods were represented within the
      psychotherapeutical and psychological research. Therefore, we analyzed 46
      Originals of a complete volume of the journal Psychotherapy, Psychosomatics,
      Psychological Medicine (PPmP). RESULT: Within the volume, 28 different analyse
      methods were applied, from which 89 per cent were directly based upon statistics.
      To be able to write and critically read Originals as a backbone of research,
      presumes a high degree of statistical education. To ignore statistics means to
      ignore research and at least to reveal the own professional work to
      arbitrariness.

PMID- 18041695
TI  - [Balancing change and mindful acceptance: the third wave of behavior therapy].

PMID- 18041696
TI  - Establishment of the European College of Veterinary Clinical Pathology (ECVCP)
      and the current status of veterinary clinical pathology in Europe.
AB  - After 5 years of development, the European College of Veterinary Clinical
      Pathology (ECVCP) was formally recognized and approved on July 4, 2007 by the
      European Board of Veterinary Specialisation (EBVS), the European regulatory body
      that oversees specialization in veterinary medicine and which has approved 23
      colleges. The objectives, committees, basis for membership, constitution, bylaws,
      information brochure and certifying examination of the ECVCP have remained
      unchanged during this time except as directed by EBVS. The ECVCP declared full
      functionality based on the following criteria: 1) a critical mass of 65 members:
      15 original diplomates approved by the EBVS to establish the ECVCP, 37 de facto
      diplomates, 7 diplomates certified by examination, and 5 elected honorary
      members; 2) the development and certification of training programs, laboratories,
      and qualified supervisors for residents; currently there are 18 resident training
      programs in Europe; 3) administration of 3 annual board-certifying examinations
      thus far, with an overall pass rate of 70%; 4) European consensus criteria for
      assessing the continuing education of specialists every 5 years; 5) organization
      of 8 annual scientific congresses and a joint journal (with the American Society
      for Veterinary Clinical Pathology) for communication of scientific research and
      information; the College also maintains a website, a joint listserv, and a
      newsletter; 6) collaboration in training and continuing education with relevant
      colleges in medicine and pathology; 7) development and strict adherence to a
      constitution and bylaws compliant with the EBVS; and 8) demonstration of
      compelling rationale, supporting data, and the support of members and other
      colleges for independence as a specialty college. Formal EBVS recognition of
      ECVCP as the regulatory body for the science and practice of veterinary clinical
      pathology in Europe will facilitate growth and development of the discipline and
      compliance of academic, commercial diagnostic, and industry laboratories in
      veterinary clinical pathology. Future needs are in developing sponsorship for
      resident positions, increasing employment opportunities, increasing compliance
      with laboratory, training, and continuing education standards, and advancing
      relevant science and technology.

PMID- 18041697
TI  - Outbreak of canine monocytic ehrlichiosis in Saudi Arabia.
AB  - BACKGROUND: Canine monocytic ehrlichiosis (CME) is a widespread tickborne
      infection of canids caused by Ehrlichia canis, a gram-negative obligatory
      intracellular bacteria belonging to the family Anaplasmataceae. CME is reported
      to have worldwide distribution, but its presence in a region requires the
      presence of the vector, the brown dog tick Rhipicephalus sanguineus. OBJECTIVE:
      This purpose of this report was to describe an outbreak of CME in a colony of
      dogs resident in the eastern region of Saudi Arabia. METHODS: History, presenting
      clinical signs, and the results of a CBC, biochemical panel, and serology (using
      a commercial test for E canis antibodies) were evaluated in 9 male Labrador
      Retrievers between October and December 2006. RESULTS: The majority of dogs
      presented with severe lethargy (7/9) and acute anorexia (5/9), and had fever
      (7/9) and generalized lymphadenopathy (7/9). The most common laboratory
      abnormalities were anemia (8/9), leukopenia (7/9), and hypoalbuminemia (6/9).
      Thrombocytopenia was found in only 2 dogs, 1 of which had increased bleeding
      tendency. Ehrlichia morulae were identified in blood films from 4/9 dogs and
      serologic test results were positive in 7/9 dogs. Confirmation of Ehrlichia sp
      infection was obtained in 1 dog by using a genus-specific real-time PCR assay.
      Four dogs had tick infestation; the ticks on 1 dog were identified as R
      sanguineus. All of the dogs had a rapid clinical response to doxycycline hyclate.
      CONCLUSIONS: This report, to our knowledge, is the first to describe the presence
      of a pathogenic Ehrlichia organism affecting dogs in Saudi Arabia. Additional
      molecular studies are necessary to confirm E canis infection, and to identify the
      strain of the organism.

PMID- 18041698
TI  - Teaching veterinary clinical pathology to undergraduate students: an integrated
      European project.
AB  - BACKGROUND: Veterinary clinical pathology is a relatively new and emerging
      discipline in Europe that has gained momentum with the recent establishment of a
      specialty college. In this situation, veterinary faculties may face challenges in
      understanding and defining what clinical pathology is and how it can best be
      integrated into existing curricula. In addition, many schools in Europe may not
      yet have available a critical mass of suitably qualified faculty capable of
      teaching in all areas of clinical pathology. OBJECTIVE: The main purpose of this
      report is to describe the goals, procedures adopted, teaching material produced,
      and proposed future activities of a major European initiative designed to develop
      a veterinary clinical pathology curriculum. METHODS: Four working subgroups were
      formed to establish a list of course objectives and topics and prepare a series
      of lectures. These contents were reviewed and discussed several times at a series
      of general meetings. RESULTS: An undergraduate course on veterinary clinical
      pathology was designed with course objectives, a list of topics and a CD-ROM
      consisting of 24 lectures. CONCLUSIONS: The results of this project could be
      useful in the establishment or improvement of training programs in veterinary
      clinical pathology at the undergraduate level in Europe and in other places
      around the world. The provision of teaching resources for faculty could help to
      instill in veterinary students a strong understanding of the discipline and
      promote development of advanced training programs and career opportunities in
      clinical pathology in Europe.

PMID- 18041699
TI  - The effect of lead poisoning on hematologic and biochemical values in trumpeter
      swans and Canada geese.
AB  - BACKGROUND: Lead is a persistent contaminant in the environment, and waterfowl
      are susceptible to lead toxicity from ingestion of lead pellets and fishing
      weights. Lead affects numerous physiologic processes through inhibition of enzyme
      activity and protein function, but its effects on commonly assessed avian blood
      values are incompletely understood. OBJECTIVES: Our aim was to evaluate
      hematologic and biochemical changes associated with blood lead concentrations in
      trumpeter swans and Canada geese. METHODS: Data for CBCs, plasma biochemical
      profiles (total protein, albumin, glucose, cholesterol, total bilirubin, calcium,
      phosphorus, gamma-glutamyltransferase [GGT], aspartate aminotransferase, lactate
      dehydrogenase, glutamate dehydrogenase, creatine kinase, amylase, and lipase),
      and whole blood lead concentrations were retrospectively analyzed for 69
      trumpeter swans and 52 Canada geese. Laboratory data obtained prospectively from
      an additional 20 trumpeter swans also were included. RBC morphology was
      semiquantitated in blood smears from 70 of the birds. Data were analyzed
      initially by ANOVA and covariance. A statistical model then was constructed to
      determine the relationship between each parameter and lead concentration.
      RESULTS: In both avian species, PCV, hemoglobin concentration, and MCHC decreased
      significantly (P < .05) with increasing blood lead concentration. Uric acid
      concentration and GGT activity were increased in trumpeter swans and phosphorus
      concentration was decreased in Canada geese in association with high blood lead
      concentration (P < .05). CONCLUSIONS: Lead toxicosis induced significant changes
      in the values of commonly measured hematologic parameters in waterfowl. These
      changes may be useful indicators of severe lead intoxication during routine
      laboratory assessment. Changes in clinical chemistry values, although
      statistically significant, were too inconsistent to serve as indicators of lead
      toxicosis.

PMID- 18041700
TI  - Hematologic characteristics of captive western barred bandicoots (Perameles
      bougainville) from Western Australia.
AB  - BACKGROUND: The western barred bandicoot (Perameles bougainville) is an
      Australian marsupial species now considered endangered as a consequence of
      habitat destruction and predation. A recently discovered papillomatosis syndrome
      is hindering efforts to repopulate this species. Hematology reference intervals
      have been lacking for P bougainville, preventing optimal interpretation of
      hematology results from wart-affected and clinically normal animals. OBJECTIVES:
      The purpose of this study was to establish hematology reference values and
      describe morphologic characteristics of blood cells of healthy western barred
      bandicoots. METHODS: Fifty-nine whole blood samples were collected by jugular
      venipuncture into EDTA from 47 clinically healthy captive western barred
      bandicoots at 3 locations on the Western Australian mainland. A CBC was performed
      using an ADVIA-120 analyzer. Data were compared on the basis of geographic
      location, sex, age, and lactation status, and reference intervals were
      calculated. Blood cell morphology was evaluated using light microscopy, and
      transmission and scanning electron microscopy. RESULTS: Significant differences
      were found based on sex (RBC indices, fibrinogen), age (% polychromatophilic
      RBCs), and geographic location (RBC, neutrophil, and lymphocyte counts, MCHC, %
      polychromatophilic RBCs, fibrinogen). Combined reference intervals were
      calculated for hemoglobin concentration (122-165 g/L), HCT (0.36-0.49 L/L), and
      total WBC (2.9-14.9 x 10(9)/L), monocyte (0-0.6 x 10(9)/L), eosinophil (0-0.9 x
      10(9)/L), and total plasma protein (47-63 g/L) concentrations. Leukocyte,
      erythrocyte, and platelet morphology were similar to those of other marsupial
      peramelid species. Nuclei in neutrophils, monocytes, and eosinophils occasionally
      had an annular configuration. CONCLUSIONS: Reference intervals and blood cell
      morphology obtained in this study will be useful for the evaluation of laboratory
      data from ill animals and assist with population health monitoring of western
      barred bandicoots.

PMID- 18041701
TI  - The relationship between blood indicators of phosphorus status in cattle.
AB  - BACKGROUND: Determining accurate body phosphorus status and requirements is
      important in ruminants because of environmental concerns of surface water
      pollution by overzealous phosphorus consumption in developed countries, and
      extensive regions of phosphorus deficiency in developing ones. Current
      indicators, such as concentrations of bone, plasma, fecal, and rumen inorganic
      phosphorus (Pi), fall short of this goal. In addition, plasma Pi (PPi)
      concentrations may be falsely increased by hemolysis during storage of blood
      samples. OBJECTIVES: The goals of this study were to: 1) compare whole blood Pi
      (WBPi), red blood cell Pi (RBCPi), and PPi concentrations in different groups of
      dairy calves and cows; 2) evaluate relationships among the concentrations of
      these indicators of phosphorus status; and 3) investigate the possibility of
      predicting RBCPi and PPi concentrations according to WBPi concentration. METHODS:
      Heparinized whole blood samples were obtained from 53 suckling calves, 29 weaned
      calves, 14 heifers, 20 dry pregnant cows, and 19 high-producing lactating dairy
      cows. Pi concentration was measured in plasma and in lysates of whole blood and
      packed RBCs using an automated phosphomolybdate method. PCV was determined using
      the microhematocrit method. Results were analyzed using 1-way ANOVA and
      regression analysis. RESULTS: Heifers and dry cows had significantly higher RBCPi
      concentrations, and weaned calves and dry cows had significantly higher WBPi
      concentrations, compared with other groups. In all groups, WBPi was significantly
      associated with other variables, including PCV. Regression models for each group
      were calculated to predict RBCPi and PPi concentrations according to WBPi
      concentration. CONCLUSION: Results of different blood phosphorus indicators vary
      according to age and stage of lactation. The models that predict PPi and RBCPi
      according to WBPi may have some value in estimating total body phosphorus status
      in cattle.

PMID- 18041702
TI  - Changes in gas composition and acid-base values of venous blood samples stored
      under different conditions in 4 domestic species.
AB  - BACKGROUND: The effect of storage temperature and time on blood gas and acid-base
      values has been investigated intensively in cattle and dogs; however, data are
      lacking in other species. OBJECTIVE: The aim of our study was to evaluate changes
      in gas composition and acid-base values in venous blood stored at different
      temperatures and for different times in 4 domestic species in Italy. METHODS:
      Blood samples from Comisana sheep (n = 10), Maltese goats (n = 10), Ragusana
      donkeys (n = 10), and Thoroughbred horses (n = 10) were analyzed after storage at
      23 degrees C (room temperature) for 15 minutes (group I), 23 degrees C for 1 hour
      (group II), 37 degrees C for 8 hours (group III), and 4 degrees C for 24 hours
      (group IV). Results were analyzed using a 1-way repeated measures ANOVA. RESULTS:
      In all species no statistically significant differences in pH values were present
      in samples stored at 4 degrees C for 24 hours. This also was true for PCO2 in all
      species except the horse. Except for HCO3- concentration in the horse,
      significant changes in PO2, HCO3- concentration, base excess, and the standard
      bicarbonate concentration were observed for all species in samples stored at 4
      degrees C. In samples stored for only 1 hour at room temperature, significant
      changes in most analytes were detected. CONCLUSIONS: The results of this study
      underline the need for rapid assessment of acid-base samples, because any delay,
      even for 1 hour, may affect the results.

PMID- 18041703
TI  - Blood coagulation times in the European brown hare (Lepus europaeus).
AB  - BACKGROUND: Many causes of mortality in the European brown hare, such as
      bacterial and viral infections, anticoagulant poisoning, and trauma, may result
      in hemorrhage. There are, however, no reference values concerning blood clotting
      in this species. OBJECTIVES: The aim of this study was to determine reference
      values for blood coagulation times and related parameters in healthy European
      brown hares. METHODS: Blood samples from 30 clinically healthy adult hares (15
      males and 15 females) were obtained. Hares were physically restrained for blood
      collection from the cephalic vein into tubes containing citrate and EDTA.
      RESULTS: Mean +/- SD were obtained for thrombin time (TT) (13.97 +/- 1.37
      seconds), prothrombin time (PT) (13.32 +/- 2.15 seconds), activated partial
      thromboplastin time (APTT) (16.73 +/- 1.86 seconds), fibrinogen concentration
      (2.98 +/- 1.06 g/L), and platelet count (355.28 +/- 128.73 x 10(9)/L).
      CONCLUSIONS: Reference values for blood coagulation times and other parameters
      associated with blood clotting will be useful in the laboratory evaluation of
      hemorrhage in the European brown hare.

PMID- 18041704
TI  - Cytologic appearance of a keloidal fibrosarcoma in a dog.
AB  - A 5-year-old neutered male, mixed-breed dog was presented with a single 4-mm,
      nodular, firm, haired subcutaneous mass on the left flank that had been present
      for approximately 2 weeks. Cytologic preparations of the mass revealed many
      spindle cells, few mast cells, rare eosinophils, rare macrophages, abundant
      hyalinized collagen, and moderate numbers of erythrocytes. The spindle cells were
      oval to fusiform, with oval nuclei, finely stippled to lacy chromatin, 1-5
      variably sized prominent nucleoli, and moderate to abundant cytoplasm with
      indistinct cell borders, wispy cytoplasmic extensions, and occasionally, fine
      magenta granulation. The cell population exhibited moderate anisocytosis,
      moderate anisokaryosis, and rare binucleation. The eosinophilic material occurred
      both in large angular aggregates with blunt ends and in amorphous aggregates with
      fine wispy projections. Histologic findings were consistent with a keloidal
      fibrosarcoma. To the authors' knowledge, this report is the first to describe the
      cytomorphologic characteristics of a keloidal fibrosarcoma in a dog.

PMID- 18041705
TI  - Prostatic sarcomatoid carcinoma in a dog: cytologic and immunohistochemical
      findings.
AB  - An 8-year-old neutered male Boxer was presented with tenesmus, hemorrhagic
      urethral discharge, and dysuria. Abdominal ultrasound and radiographic
      examinations revealed irregular prostatic enlargement. Laparotomy was performed
      and intraoperative cytology was done on imprint smears of a biopsy specimen
      obtained from a prostatic mass. The cytologic preparation was highly cellular and
      contained a predominant population of atypical, large, loosely cohesive spindle
      cells, with rare multinucleated cells and mitotic figures. The cytologic findings
      were consistent with undifferentiated sarcoma. At necropsy, a large cystic
      prostatic mass and numerous satellite nodules in the soft tissues around the
      pelvis were found. On histologic examination the tumor was composed primarily of
      bundles of neoplastic spindle cells. Rare pseudo-acinar structures and signet
      ring cells also were observed. On immunohistochemical examination, the neoplastic
      cells co-expressed cytokeratin and vimentin. Based on histologic and
      immunohistochemical findings, the tumor was diagnosed as primary prostatic
      sarcomatoid carcinoma. This is a rare tumor in dogs, in which biphasic morphology
      of epithelial and mesenchymal cells can complicate the diagnosis, requiring
      immunochemical stains for confirmation.

PMID- 18041706
TI  - Pure white cell aplasia in a dog.
AB  - A 3-year-old Irish Wolfhound was evaluated because of acute onset of lethargy and
      fever. Severe neutropenia (0/microL; reference interval 2500-11,200/microL) was
      associated with granulocyte aplasia in the bone marrow (myeloid:erythroid ratio,
      0.009:1). Antineutrophil antibodies were assessed by an indirect
      immunofluorescence assay using flow cytometry. When normal canine leukocytes were
      incubated with the patient's serum and anti-IgG, a marked shift was observed in
      the forward-angle light scatter of the neutrophil population, and the monocyte
      cluster disappeared, possibly the result of fragmentation or lysis. Both
      neutrophil fluorescence intensity (309 +/- 11 median channel units [MCU], control
      values 107-152 MCU) and the percentage of neutrophils with increased fluorescence
      intensity (61 +/- 5%, control values 3.8-13.7%) were increased in the patient's
      serum, consistent with the presence of antineutrophil antibodies. Repeated
      episodes of neutropenia occurred while treatment with steroidal and nonsteroidal
      immunosuppressive therapy was initiated and modified. The neutrophil count
      eventually stabilized in the low-normal range, and the dog was maintained for the
      next 15 months on prednisone (0.4 mg/kg PO q 48 h) and azathioprine (2 mg/kg
      daily). During this period, the dog developed immune-mediated hemolytic anemia
      and thrombocytopenia, decubital ulcers, nasal aspergillosis, and eventually,
      multi-organ septicemia, which led to euthanasia on day 784. A diagnosis of pure
      white cell aplasia was made in this dog, based on the many similarities to human
      patients with pure white cell aplasia, including severe neutropenia with
      selective granulocyte aplasia, serum antineutrophil antibodies, remission
      dependent on treatment with immunosuppressive therapy, and recurrent bacterial
      infections.

PMID- 18041707
TI  - Hypercalcemia and high parathyroid hormone-related peptide concentration in a dog
      with a complex mammary carcinoma.
AB  - A 10-year-old female Dachshund was presented with a history of mammary masses,
      slight lethargy, polyuria, and polydipsia. Physical examination findings included
      masses involving the first, second, and fourth mammary glands of the left side.
      The mandibular, axillary, and right popliteal lymph nodes were mildly enlarged.
      Serum chemistry results included hypercalcemia (13.9 mg/dL, reference interval
      8.0-11.5 mg/dL). Although intact parathyroid hormone (PTH) concentration (1.05
      pmol/L) was below the reference interval (2-13 pmol/L), PTH-related protein
      (PTHrP) concentration was markedly increased (9.40 pmol/L, reference value < 2
      pmol/L). The masses were surgically removed, and the histopathologic diagnosis
      was complex mammary carcinoma. Three weeks after surgery, serum total calcium
      concentration had decreased to 10.5 mg/dL. Resolution of the hypercalcemia and
      clinical signs supported a diagnosis of humoral hypercalcemia of malignancy
      associated with mammary gland carcinoma.

PMID- 18041708
TI  - Cerebrospinal fluid from a dog with hind limb ataxia.
AB  - A 9-year-old spayed female German Shepherd dog with a history of orthopedic
      disease was presented to the North Carolina State University Veterinary Teaching
      Hospital for evaluation of recent, progressive, bilateral, hindlimb ataxia.
      Analysis of cisternal and lumbar cerebrospinal fluid (CSF) samples revealed
      normal total nucleated cell counts and a mild increase in protein concentration
      in the lumbar sample. In cytocentrifuged specimens of both CSF samples,
      aggregates of refractile, angular to irregular, pale blue to colorless,
      crystalline material were observed in the background. Some of the material
      appeared birefringent under polarized light. Differentials for the material
      included contrast agent, epidural anesthetics or other pharmacologic agents, or
      artifact introduced through sample processing, collection, or handling. Based on
      investigation of clinical and laboratory processes it was determined that tubes
      used to collect CSF in the hospital recently had been changed from additive-free
      glass tubes to silica-coated shatter-resistant plastic tubes (BD Vacutainer Plus
      serum tubes, silicone-coated, Becton Dickinson). A cytocentrifuged preparation of
      saline placed in a silica-coated tube contained crystalline material identical to
      that observed in the CSF samples; saline placed in an additive-free glass tube
      contained no material. In this case, we document the microscopic appearance of
      highly concentrated silica particles in cytocentrifuged preparations of CSF and
      underscore the importance of recognizing and identifying this artifact in
      cytologic preparations.

PMID- 18041709
TI  - Solubilization and bioconjugation of QDs and their application in cell imaging.
AB  - Quantum dot (QD) solubilization, conjugation with biomolecules, column
      purification, and labeling of human HepG2 cells with transferrin-QD (Tf-QD)
      conjugates are reported in detail in this article. Water-soluble QDs (WQDs) were
      obtained using sodium thiolycolate to replace the surface ligand tri-n
      octylphosphine oxide (TOPO) on the surface of oil-soluble QDs, and Tf-QD
      conjugates were produced by coupling Tf to WQD. The resulting Tf-QDs were
      characterized by UV and luminescence spectrophotometry and purified by Sephadex
      column. The results indicate that Tf has been conjugated to QD successfully.
      Based on transferrin/transferrin-receptor-mediated delivery system, the Tf-QD
      conjugates were used to label human HepG2 cells. After a short incubation, the
      QDs were mainly localized to the membrane of cells. After 12-h incubation, QDs
      appear mainly in the cytoplasm portion. However, QDs were not found in the
      nucleus of the cells. Furthermore, the fluorescence intensity of QDs in the cells
      reduces gradually over time, and fluorescence cannot be observed after 10 days.
      However, the growth of the labeled cells was not markedly affected by the
      toxicity of QDs, and they are alive for 10 days. These results can be used for
      further application of QDs in bioscience.

PMID- 18041710
TI  - Apparent conversion of adhesive resin in the hybrid layer, Part 1: Identification
      of an internal reference for Raman spectroscopy and the effects of water storage.
AB  - Monomer conversion of adhesives in the hybrid layer is important to the quality
      and longevity of the dentin bond. In this study, degree of conversion and
      relative co-monomer concentrations of both experimental and commercial adhesive
      resins were determined using Raman spectroscopy. The objectives were to identify
      stable Raman scattering peaks to use as internal references and to determine the
      effect of water storage on measured conversion and co-monomer concentrations. The
      peak at 605 cm(-1) did not change throughout polymerization and is associated
      with monomers in both adhesives. This peak was used as an internal reference for
      conversion and composition calculations before and after water storage.
      Conversion of the adhesive resins immediately after photopolymerization was
      approximately 20% lower than that measured after 24-h water storage. HEMA
      concentration (relative to bis-GMA) in the adhesive resins immediately after
      photopolymerization was at least 5 wt % higher than that measured after 24-h
      water storage. Elution of unreacted HEMA provides a reasonable explanation for
      the "supposed" change in conversion measurements, which is more appropriately
      described as apparent conversion. This apparent conversion will impact
      interpretation of physical properties and structure of the polymer, as well as
      increase the probability of water penetration and its reaction within the hybrid
      layer.

PMID- 18041711
TI  - In vitro engineering of a palatal mucosa equivalent with acellular porcine dermal
      matrix.
AB  - The objective of this study was to develop a palatal mucosa equivalent composed
      of multilayered oral keratinocytes grown on the acellular porcine dermal matrix.
      Acellular porcine dermal matrix was prepared through a series of procedures and
      assessed by histological, immunohistochemical, and scanning electron microscopy
      examination. The palatal mucosa equivalent was fabricated by seeding oral
      keratinocytes, which cultured from human palate mucosa, onto the acellular dermal
      matrix. After 4 days submerged in medium, this composite was raised to the air
      liquid interface for another 7 or 14 days of cultivation. The results
      demonstrated the processed porcine dermal matrix was totally cell-free. The
      resultant palatal mucosa equivalent showed a multilayered oral epithelium that
      had been formed, and the number of cell layers was correlated with the culture
      period at the air-liquid interface. Oral keratinocytes infiltrated into the empty
      hair follicles of the acellular porcine dermal matrix and formed an anchor-like
      structure, which exhibited resemblance to the rete ridges of the native palate
      mucosa. Immunohistochemical staining for CK10/13, CK19, Ki-67 nuclear antigen,
      and Heparan sulphate indicated the cultured palatal mucosa equivalent shared the
      same characteristics with that of the native palate mucosa. In conclusion, our
      fabricated palatal mucosa equivalent exhibited the characteristics of the native
      counterpart, and this equivalent might be useful for recovery of the wounds in
      the palate secondary to palatoplasty.

PMID- 18041713
TI  - Leptin's mitogenic effect in human liver cancer cells requires induction of both
      methionine adenosyltransferase 2A and 2beta.
AB  - Leptin is an adiopokine that plays a pivotal role in the progression of liver
      fibrogenesis and carcinogenesis. Recently, leptin was shown to be mitogenic in
      human liver cancer cell lines HepG2 and Huh7. Whether leptin can act as a mitogen
      in normal hepatocytes is unclear. Methionine adenosyltransferase (MAT) is an
      essential enzyme that catalyzes the formation of S-adenosylmethionine (SAMe), the
      principal methyl donor and precursor of polyamines. Two genes (MAT1A and MAT2A)
      encode for the catalytic subunit of MAT, whereas a third gene (MAT2beta) encodes
      for a regulatory subunit that modulates the activity of MAT2A-encoded isoenzyme.
      The aims of this study were to examine whether leptin's mitogenic activity
      involves MAT2A and MAT2beta and whether this can be modulated. We found that
      leptin is mitogenic in HepG2 cells but not in primary human or mouse hepatocytes.
      Leptin induced the expression of MAT2A and MAT2beta in HepG2 cells and normal
      human and mouse hepatocytes, but although it increased SAMe level in HepG2 cells,
      it had no effect on SAMe level in normal hepatocytes. Leptin-mediated induction
      of MAT genes and growth in HepG2 cells required activation of extracellular
      signal-regulated kinase and phosphatidylinositol-3-kinase signaling pathways.
      Treatment with SAMe or its metabolite methylthioadenosine (MTA) lowered
      expression of MAT2A and MAT2beta and blocked leptin-induced signaling, including
      an increase in MAT gene expression and growth. Increased expression of MAT2A and
      MAT2beta is required for leptin to be mitogenic, although by entirely different
      mechanisms. CONCLUSION: Leptin induces MAT2A and MAT2beta expression in HepG2
      cells and normal hepatocytes but is mitogenic only in HepG2 cells.
      Pharmacological doses of SAMe or MTA lower expression of both MAT2A and MAT2beta
      and interfere with leptin signaling.

PMID- 18041714
TI  - Interacting alleles of the coinhibitory immunoreceptor genes cytotoxic T
      lymphocyte antigen 4 and programmed cell-death 1 influence risk and features of
      primary biliary cirrhosis.
AB  - Autoimmune diseases such as primary biliary cirrhosis (PBC) result from failure
      in the immune mechanisms that establish and maintain self-tolerance. Evidence
      suggests that these processes are shared among the spectrum of autoimmune
      syndromes and are likely genetically determined. Cytotoxic T-lymphocyte antigen 4
      (CTLA4) and programmed cell-death 1 (PDCD1) are two genes encoding coinhibitory
      immunoreceptors that harbor polymorphisms with demonstrated associations to
      multiple autoimmune disorders. We aimed to assess functional single nucleotide
      polymorphisms (SNPs) in these two genes for association with PBC. SNPs in CTLA4
      and PDCD1 were genotyped in 351 PBC patients and 205 controls. Allele and
      genotype frequencies were evaluated for association with PBC and/or
      antimitochondrial antibody (AMA) positivity with logistic regression. Haplotypes
      were inferred with an expectation-maximization algorithm, and allelic interaction
      was analyzed by logistic regression modeling. Individual SNPs demonstrated no
      association to PBC. However, the GG genotype of CTLA4 49AG was significantly
      associated with AMA positivity among the PBC patients. Also, individual SNPs and
      a haplotype of CTLA4 as well as a rare genotype of the PDCD1 SNP PD1.3 were
      associated with orthotopic liver transplantation. As well, we identified the
      influence of an interaction between the putatively autoimmune-protective CTLA4
      49AG:CT60 AA haplotype and autoimmune-risk PDCD1 PD1.3 A allele on development of
      PBC. CONCLUSION: Our findings illustrate the complex nature of the genetically
      induced risk of PBC and emphasize the importance of considering definable
      subphenotypes of disease, such as AMA positivity, or definitive measures of
      disease severity/progression, like orthotopic liver transplantation, when genetic
      analyses are being performed. Comprehensive screening of genes involved with
      immune function will lead to a greater understanding of the genetic component of
      autoimmunity in PBC while furthering our understanding of the pathogenic
      properties of this enigmatic disease.

PMID- 18041715
TI  - CXCL10 regulates liver innate immune response against ischemia and reperfusion
      injury.
AB  - We have shown that activation of toll-like receptor 4 (TLR4) and its interferon
      regulatory factor 3 (IRF3)-dependent downstream signaling pathway are required
      for the development of liver ischemia/reperfusion injury (IRI). This study
      focused on the role of TLR4-IRF3 activation pathway products, in particular,
      chemokine (C-X-C motif) ligand 10 (CXCL10). The induction of CXCL10 by liver IR
      was rapid (1 hour postreperfusion), restricted (ischemic lobes), and specific (no
      CXCL9 and CXCL11 induction). Functionally, CXCL10 was critical for IR-induced
      liver inflammation and hepatocellular injury. CXCL10 knockout (KO) mice were
      protected from IRI, as evidenced by reduced serum alanine aminotransferase (sALT)
      levels and preserved liver histological detail. The induction of pro-inflammatory
      genes, such as tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL
      1beta), IL-6, and IL-12beta was diminished, whereas the induction of the IL-10
      gene remained intact in CXCL10 KO mice, indicating an altered liver response
      against IR. This was accompanied by selective down-regulation of extracellular
      signal-regulated kinase (ERK), but intact Jun N-terminal kinase (JNK), activation
      in the KO IR livers. This altered liver inflammation response was (1) specific to
      IR, because lipopolysaccharide (LPS) induced a comparable pro-inflammatory
      response in CXCL10 KO and wild-type (WT) mice; and (2) responsible for liver
      cytoprotection from IR, because neutralization of IL-10 restored local
      inflammation and hepatocellular damage. CONCLUSION: CXCL10 regulates liver
      inflammation response against IRI, and its deficiency protected livers from IRI
      by local IL-10-mediated cytoprotection. Targeting CXCL10 may provide a novel
      therapeutic means to ameliorate liver IRI in clinics.

PMID- 18041717
TI  - Enhancement of bio-compatibility via specific interactions in polyesters modified
      with a bio-resourceful macromolecular ester containing polyphenol groups.
AB  - Specific interactions and miscibility are demonstrated in a series of binary
      miscible blend comprising of bio-compatible/biodegradable polyesters, such as
      poly(epsilon-caprolactone) (PCL), poly(ethylene adipate) (PEA), or poly (butylene
      adipate) (PBA), and a macromolecular ester with polyphenol groups, tannic acid
      (TA). Thermal analysis and infrared spectroscopy were used for proving existence
      of favorable interactions, and polarized-light optical microscopy was used for
      characterizing the changes in crystal growth. The appearance of a single
      composition-dependent glass transition temperature (T(g)) observed by
      differential scanning calorimetry (DSC) indicated that TA is miscible with PCL,
      PBA, and PEA, respectively, over the entire range of compositions. Fourier
      transform infrared (FTIR) spectroscopy confirmed the presence of specific
      intermolecular hydrogen bonding interactions between the carbonyl groups of
      polyesters and the phenolic hydroxyl groups of TA. The blend T(g)'s generally
      exhibited various extents of positive-then-negative deviation from linearity with
      the compositions. The T(g)-composition relationships for three blend systems
      could all be fitted by the Kwei equation with large negative q values of -80 to 
      110 for different polyesters. Significant effects by TA on the spherulitic
      crystallization growth in the polyester/TA blends were also discussed to support
      the miscibility and strong interactions. Overall, the behavior of blends of
      polyesters with TA is similar to that of blends of polyesters with poly(vinyl p
      phenol) (PVPh) that have been more widely studied and reported. However, TA is
      naturally bio-resourceful, bio-compatible, and bio-degradable but PVPh is not.
      Synergism of miscibility, natural bio-compatibility, and biodegradability in
      these blends by introducing naturally biodegradable macromolecules such as TA may
      offer greater potential in intended applications.

PMID- 18041716
TI  - Limbic dysregulation is associated with lowered heart rate variability and
      increased trait anxiety in healthy adults.
AB  - OBJECTIVES: We tested whether dynamic interaction between limbic regions supports
      a control systems model of excitatory and inhibitory components of a negative
      feedback loop, and whether dysregulation of those dynamics might correlate with
      trait differences in anxiety and their cardiac characteristics among healthy
      adults. EXPERIMENTAL DESIGN: Sixty-five subjects received fMRI scans while
      passively viewing angry, fearful, happy, and neutral facial stimuli. Subjects
      also completed a trait anxiety inventory, and were monitored using ambulatory
      wake ECG. The ECG data were analyzed for heart rate variability, a measure of
      autonomic regulation. The fMRI data were analyzed with respect to six limbic
      regions (bilateral amygdala, bilateral hippocampus, Brodmann Areas 9, 45) using
      limbic time-series cross-correlations, maximum BOLD amplitude, and BOLD amplitude
      at each point in the time-series. PRINCIPAL OBSERVATIONS: Diminished coupling
      between limbic time-series in response to the neutral, fearful, and happy faces
      was associated with greater trait anxiety, greater sympathetic activation, and
      lowered heart rate variability. Individuals with greater levels of trait anxiety
      showed delayed activation of Brodmann Area 45 in response to the fearful and
      happy faces, and lowered Brodmann Area 45 activation with prolonged left amygdala
      activation in response to the neutral faces. CONCLUSIONS: The dynamics support
      limbic regulation as a control system, in which dysregulation, as assessed by
      diminished coupling between limbic time-series, is associated with increased
      trait anxiety and excitatory autonomic outputs. Trait-anxious individuals showed
      delayed inhibitory activation in response to overt-affect stimuli and diminished
      inhibitory activation with delayed extinction of excitatory activation in
      response to ambiguous-affect stimuli.

PMID- 18041718
TI  - Sub-micron and nanoscale feature depth modulates alignment of stromal fibroblasts
      and corneal epithelial cells in serum-rich and serum-free media.
AB  - Topographic features are generally accepted as being capable of modulating cell
      alignment. Of particular interest is the potential that topographic feature
      geometry induces cell alignment indirectly through impacting adsorbed proteins
      from the cell culture medium on the surface of the substrate. However, it has
      also been reported that micron-scale feature depth significantly impacts the
      level of alignment of cellular populations on topography, despite being orders of
      magnitude larger than the average adsorbed protein layer (nm). In order to better
      determine the impact of biomimetic length scale topography and adsorbed protein
      interaction on cellular morphology we have systematically investigated the effect
      of combinations of sub-micron to nanoscale feature depth and lateral pitch on
      corneal epithelial cell alignment. In addition we have used the unique properties
      of a serum-free media alternative in direct comparison to serum-rich medium to
      investigate the role of culture medium protein composition on cellular alignment
      to topographically patterned surfaces. Our observation that increasing groove
      depth elicited larger populations of corneal epithelial cells to align regardless
      of culture medium composition and of cell orientation with respect to the
      topography, suggests that these cells can sense changes in topographic feature
      depths independent of adsorbed proteins localized along ridge edges and tops.
      However, our data also suggests a strong combinatory effect of topography with
      culture medium composition, and also a cell type dependency in determining the
      level of cell elongation and alignment to nanoscale topographic features.

PMID- 18041720
TI  - Heparin modification of calcium phosphate bone cements for VEGF
      functionalization.
AB  - A promising strategy to promote angiogenesis within an engineered tissue is the
      local and sustained delivery of an angiogenic factor by the substitute itself.
      Recently, we reported on functionalization of Biocement D (BioD) and several
      modifications of this calcium phosphate bone cement with vascular endothelial
      growth factor (VEGF). Maintenance of biological activity of VEGF after release
      from the cement was improved by modification of BioD with mineralized collagen
      type I (BioD/coll). However, BioD/coll composites showed a higher initial burst
      of VEGF release than do the unmodified BioD. In the present study, VEGF release
      from BioD/coll composites modified with different amounts of heparin was
      investigated. We found a distinct reduction of the initial burst of release by
      adding heparin in a concentration-dependent manner. Moreover, the heparin
      modification had a positive impact on the biological activity of released VEGF.
      An advancement of biological properties of BioD/coll by addition of heparin was
      further shown by improved adhesion of endothelial cells on the cement surface.
      Characterization of material properties of the heparin-modified BioD/coll
      composites revealed a finer microstructure with smaller HA-particles and a higher
      specific surface area than heparin-free BioD/coll. However, higher amounts of
      heparin resulted in a reduced compressive strength. The rheological properties of
      these cement pastes have been found to be favorable for good handling
      particularly with regard to their clinical application.

PMID- 18041719
TI  - Pre-treatment of synthetic elastomeric scaffolds by cardiac fibroblasts improves
      engineered heart tissue.
AB  - Native myocardium consists of several cell types, of which approximately one
      third are myocytes and most of the nonmyocytes are fibroblasts. By analogy with
      monolayer culture in which fibroblasts were removed to prevent overgrowth, early
      attempts to engineer myocardium utilized cell populations enriched for cardiac
      myocytes (CMs; approximately 80-90% of total cells). We hypothesized that the pre
      treatment of synthetic elastomeric scaffolds with cardiac fibroblasts (CFs) will
      enhance the functional assembly of the engineered cardiac constructs by creating
      an environment supportive of cardiomyocyte attachment and function. Cells
      isolated from neonatal rat ventricles were prepared to form three distinct
      populations: rapidly plating cells identified as CFs, slowly plating cells
      identified as CMs, and unseparated initial population of cells (US). The cell
      fractions (3 x 10(6) cells total) were seeded into poly(glycerol sebacate)
      scaffolds (highly porous discs, 5 mm in diameter x 2-mm thick) using
      Matrigeltrade mark, either separately (CM or CF), concurrently (US), or
      sequentially (CF pre-treatment followed by CM culture, CF + CM), and cultured in
      spinner flasks. The CF + CM group had the highest amplitude of contraction and
      the lowest excitation threshold, superior DNA content, and higher glucose
      consumption rate. The CF + CM group exhibited compact 100- to 200-mum thick
      layers of elongated myocytes aligned in parallel over layers of collagen
      producing fibroblasts, while US and CM groups exhibited scattered and poorly
      elongated myocytes. The sequential co-culture of CF and CM on a synthetic
      elastomer scaffold thus created an environment supportive of cardiomyocyte
      attachment, differentiation, and contractile function, presumably due to scaffold
      conditioning by cultured fibroblasts. When implanted over the infarcted
      myocardium in a nude rat model, cell-free poly(glycerol sebacate) remained at the
      ventricular wall after 2 weeks of in vivo, and was vascularized.

PMID- 18041721
TI  - Oscillatory perfusion seeding and culturing of osteoblast-like cells on porous
      beta-tricalcium phosphate scaffolds.
AB  - Perfusion culture systems have proven to be effective bioreactors for
      constructing tissue engineered bone in vitro, but existing circuit-based
      perfusion systems are complicated and costly for conditioned culture due to the
      large medium volume required. A compact perfusion system for artificial bone
      fabrication using oscillatory flow is described here. Mouse osteoblast-like MC
      3T3-E1 cells were seeded at 1.5 x 10(6) cells/100 microL and cultured for 6 days
      in porous ceramic beta-tricalcium phosphate scaffolds (10 mm in diameter, 8 mm in
      height) by only 1.5 mL culture media per scaffold. The seeding efficiency, cell
      proliferation, distribution and viability, and promotion of early osteogenesis by
      both a static and an oscillatory perfusion method were evaluated. The oscillatory
      perfusion method generated higher seeding efficiency, alkaline phosphatase
      activity, and scaffold cellularity (by DNA content) after 6 days of culture.
      Stereomicroscopic observation of 3(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide staining and Calcein-AM/propidium iodide double
      staining also demonstrated homogeneous seeding, proliferation, and viability of
      cells throughout the scaffolds in the oscillatory perfusion system. By contrast,
      the static culture yielded polarized seeding and proliferation favoring the outer
      and upper scaffold surfaces, with only dead cells in the center of the scaffolds.
      Thus, these results suggest that the oscillatory flow condition not only allow a
      better seeding efficiency and homogeneity, but also facilitates uniform culture
      and early osteogenic differentiation. The oscillatory perfusion system could be a
      simple and effective bioreactor for bone tissue engineering.

PMID- 18041722
TI  - Adhesion of staphylococcal and Caco-2 cells on diamond-like carbon polymer hybrid
      coating.
AB  - Staphylococci cause the majority of the nosocomial implant-related infections
      initiated by adhesion of planktonic bacteria to the implant surface. It was
      hypothesized that plasma accelerating filtered pulsed arc discharge method
      enables combination of the advantageous properties of diamond with the
      antisoiling properties of polymers. Diamond-like carbon polytetrafluoroethylene
      hybrid (DLC-PTFE-h) coating was produced. The adhesion of S. aureus ATCC 25923
      (10(8) colony-forming units/mL) to surfaces diminished from 2.32%, 2.35%, and
      2.57% of high quality DLC, titanium, and oxidized silicon, respectively, to 1.93%
      of DLC-PTFE-h. For S. epidermidis ATCC 35984 the corresponding figures were
      3.90%, 3.32%, 3.47%, and 2.57%. Differences in bacterial adhesion between
      recombinant DLC-PTFE-h and other materials were statistically significant (p <
      0.05). In contrast, human Caco-2 cells adhered as well to DLC-PTFE-h as to DLC,
      titanium, or silicon, which were all in the MTT test found to be cytocompatible.
      DLC-PTFE-h coating can be used to modify the surface properties of any surgical
      implants and is an unfavorable substrate for staphylococcal cells, but compatible
      with human Caco-2 cells. DLC-PTFE-h coating may help in the combat against
      Staphylococcus-related implant infections which usually require both antibiotics
      and surgical removal of the implant for cure.

PMID- 18041723
TI  - The effect of combined application of TGFbeta-1, BMP-2, and COLLOSS E on the
      development of bone marrow derived osteoblast-like cells in vitro.
AB  - This study investigated the combined application of Transforming Growth Factor
      beta-1 (TGFbeta-1) and Bone Morphogenetic Protein-2 (BMP-2) to stimulate
      osteogenic expression in vitro. TGFbeta-1 and BMP-2 fulfill specific roles in the
      formation of new bone. COLLOSS E, a bone-derived collagen product containing a
      variety of naturally occurring growth factors, was also used. Growth factors were
      administered to osteoblast-like cells from rat bone marrow (RBM). Proliferation
      and differentiation were monitored up to 24 days, by measuring total DNA content,
      alkaline phosphatase activity, and calcium content. Genetic expression of a set
      of differentiation markers at day 7 was measured by Q-PCR. Adding BMP-2 alone
      induced high proliferation rates, compared to the growth factor supplemented
      groups, and it induced high differentiation rates, compared to the control group.
      Adding TGFbeta-1 combined with BMP-2, TGFbeta-1 alone, or COLLOSS E resulted in a
      significant decrease in proliferation rate, but an increase in differentiation
      rate, compared to the control group. Additive or synergistic effects of
      application of TGFbeta-1 and BMP-2 were not observed. The observed effects of
      COLLOSS E mainly resembled those of TGFbeta-1 application alone. It can be
      concluded that BMP-2 is the most suitable candidate for osteogenic stimulation of
      RBM cells in these settings.

PMID- 18041724
TI  - Hemocompatible albumin-heparin coatings prepared by the layer-by-layer technique.
      The effect of layer ordering on thrombin inhibition and platelet adhesion.
AB  - Using the layer-by-layer technique, ELISA polystyrene plates were coated with
      multilayer assemblies of albumin with various heparins or with multilayer
      assemblies of albumin. The coatings containing heparin were tested for their
      ability to potentiate thrombin inhibition by antithrombin and its dependence on
      the layer arrangement. The order of activities of surface bound heparins matched
      their order in solution; however their activity was reduced to less than 10% due
      to binding. The increasing number of layers increased the activity of the
      coatings suggesting that heparin inside the assemblies is available for the
      interaction. The albumin-heparin assemblies overcoated with albumin layers
      preserved about half of heparin activity. Platelets adhered in similar amounts to
      albumin-heparin and albumin coatings; however, in both cases platelets adhered
      more to single layer than to multilayer coatings. The adhesion of platelets to
      single layer coatings was also affected by the crosslinking of the coatings; more
      platelets adhered to less crosslinked single layer coatings while multilayer
      coatings remained essentially unaffected by crosslinking. If the coatings were
      dried and reswollen, a substantial number of platelets adhered to the
      reconditioned single layer coatings but the two layer coatings were affected much
      less and the adhesion of platelets to the coatings with three layers was close to
      normal. A minimum of three albumin-heparin or albumin layers is apparently
      required to shield the underlying surface and to achieve proper functioning of
      the coatings.

PMID- 18041725
TI  - In vitro cytotoxicity of single-walled carbon nanotube/biodegradable polymer
      nanocomposites.
AB  - Injectable nanocomposites made of biodegradable poly(propylene fumarate) and the
      crosslinking agent propylene fumarate-diacrylate as well as each of three forms
      of single-walled carbon nanotubes (SWNTs) were evaluated for their in vitro
      cytotoxicity. Unreacted components, crosslinked networks, and degradation
      products of the nanocomposites were investigated for their effects on cell
      viability using a fibroblast cell line in vitro. The results did not reveal any
      in vitro cytotoxicity for purified SWNTs, SWNTs functionalized with 4-tert
      butylphenylene, and ultra-short SWNTs at 1- 100 microg/mL concentrations.
      Moreover, nearly 100% cell viability was observed on all crosslinked
      nanocomposites and cell attachment on their surfaces was comparable with that on
      tissue culture polystyrene. The degradation products of the nanocomposites
      displayed a dose-dependent adverse effect on cells, which was partially due to
      increased osmolarity by the conditions of accelerated degradation and could be
      overcome at diluted concentrations. These results demonstrate that all three
      tested nanocomposites have favorable cytocompatibility for potential use as
      scaffolds for bone tissue engineering applications.

PMID- 18041726
TI  - Potential of baboon endothelial progenitor cells for tissue engineered vascular
      grafts.
AB  - Thrombosis and intimal hyperplasia limit the usefulness of small caliber vascular
      grafts. While some improvements have been reported for grafts seeded with mature
      endothelial cells (EC), the harvesting of ECs from autologous sources, for
      example, veins or adipose tissue, remains problematic. More recently, endothelial
      progenitor cells (EPCs) have been considered a promising source of ECs because
      EPCs can be readily isolated from whole blood then rapidly expanded in vitro.
      Additionally, EPCs are increasingly recognized to play important roles in
      hemostasis, angiogenesis, and arterial injury repair. However, the
      characterization of EPCs in relevant animal models remains poorly defined.
      Accordingly, we have characterized the isolation, growth, and functional
      characteristics of Baboon EPCs (BaEPCs) to evaluate their potential for an
      autologous cell source for tissue engineered vascular grafts. BaEPCs were
      successfully cultured from the peripheral blood with an average population
      doubling time of 1.17 +/- 0.43 days. While the BaEPCs were positive for typical
      EC markers of vWF, CD31, VE-cadherin, VEGF-R2, Thrombomodulin, and E-selectin,
      there was reduced eNOS expression. The BaEPCs cell body and actin filaments align
      in the direction of flow typical of mature ECs. Thus while the lack of eNOS
      expression is worthy of investigation, EPCs are an attractive cell source for
      tissue engineered vascular grafts and the baboon model has great potential for
      continuing evaluations of these cells.

PMID- 18041727
TI  - Self-assembling cyclodextrin based hydrogels for the sustained delivery of
      hydrophobic drugs.
AB  - This study aims to investigate the rheological properties of self-assembling gels
      containing cyclodextrins with potential application as injectable matrix for the
      sustained delivery of poorly soluble drugs. The ability of these gels to entrap
      two hydrophobic molecules, benzophenone (BZ) and tamoxifen (TM), and to allow
      their in vitro sustained release was evaluated. In view of their future
      pharmaceutical use, gels were sterilized by high hydrostatic pressures (HHP) and
      tested for their biocompatibility. The gels formed instantaneously at room
      temperature, by mixing the aqueous solutions of two polymers: a beta-cyclodextrin
      polymer (pbetaCD) and a hydrophobically modified dextran by grafting alkyl side
      chains (MD). MD-pbetaCD gels presented a viscoelastic behavior under low shear,
      characterized by constant values of the loss modulus G'' and the storage modulus
      G'. The most stable gels were obtained for a total polymer concentration C(p) of
      6.6% and 7.5% (w/w), and a polymer ratio MD/pbetaCD of 50/50 and 33/67 (w/w). BZ
      and TM were successfully incorporated into MD-pbetaCD gels with loading
      efficiencies as high as 90%. In vitro, TM and BZ were released gradually from the
      gel matrix with less than 25% and 75% release, respectively, after 6 days
      incubation. HHP treatment did not modify the rheological characteristics of MD
      pbetaCD gels. Moreover, the low toxicity of these gels after intramuscular
      administration in rabbits makes them promising injectable devices for local
      delivery of drugs.

PMID- 18041728
TI  - Biocompatibility and gelation of chitosan-glycerol phosphate hydrogels.
AB  - The aim of this study was to evaluate the cytotoxicity and gelation of
      thermosensitive chitosan-beta-glycerol phosphate (GP) solutions, which undergo
      sol-gel transition around body temperature. Chitosan 0.5-2% (w/v) mixed with GP 5
      20% (w/v) solutions all gel at 37 degrees C and possess pH around the
      physiological range. High GP and chitosan concentrations result in faster
      gelation time. Extracts of all chitosan concentrations mixed with or without 5%
      (w/v) GP and 2% (w/v) chitosan combined with 10% (w/v) GP demonstrated up to 34%
      increase in proliferation rate of goat bone marrow derived mesenchymal stem cells
      when compared with control medium. Extracts from all other chitosan-GP
      combinations resulted in reduced cell proliferation relative to control medium.
      Increasing GP content in the gel resulted in a linear increase in the osmolality
      of the extracts in contact with the gels. The results of this study indicate that
      chitosan-GP is a biocompatible hydrogel, extracts of which can stimulate
      mesenchymal stem cell proliferation at certain concentrations. This material is
      therefore a promising vehicle for cell encapsulation and injectable tissue
      engineering applications.

PMID- 18041729
TI  - Heparin-conjugated star-shaped PLA for improved biocompatibility.
AB  - Star-shaped PLA-heparin (sPLA-Hep) was prepared by coupling heparin to the star
      shaped PLA (sPLA) reaction using carbonyldiimidazole (CDI) chemistry. Hydroxyl
      groups of sPLA were activated by CDI for the reaction with the remained amino
      terminal groups of heparin. The surface heparin content of sPLA-Hep was measured
      to be 1.43 microg/cm(2). sPLA-Hep-coated surface has shown higher hydrophilicity
      than control surface. The clotting time of sPLA-Hep measured by activated partial
      thromboplastin time (APTT) was significantly prolonged when compared with sPLA
      and linear PLA-Hep. sPLA-Hep surface demonstrated lower protein adsorption and
      platelet adhesion than control sPLA surface. In addition, fibroblast culture on
      the sPLA-Hep surface showed the enhanced cell spreading area compared with the
      sPLA surface. Obtained results suggest that the incorporation of heparin to sPLA
      is effective in curtailing the surface induced-thrombosis and in manipulating the
      cell interaction. sPLA-Hep could be applied as blood/tissue compatible
      biodegradable materials for implantable medical devices and tissue engineering.

PMID- 18041730
TI  - Factors influencing the properties of reconstituted collagen fibers prior to self
      assembly: animal species and collagen extraction method.
AB  - This research work allows a direct comparison between collagen solutions of equal
      concentration derived from the two widely used collagen sources: bovine Achilles
      tendon (BAT) and rat tail tendon (RTT), and extraction methods: acid (AS) and
      pepsin (PS) solubilization on the properties of extruded collagen fibers.
      Scanning electron microscopy revealed that the substructure of the collagen
      fibers was the same independent of the treatment. Transmission electron
      microscopy revealed that the AS collagen-derived fibers were comprised of thick
      quarter-staggered fibrils, while the coexistence of thin nonbanded and thick
      banded fibrils was apparent for the PS collagen-derived fibers. The BAT-derived
      fibers demonstrated higher denaturation temperature than the RTT-derived ones (p
      < 0.05). The extraction method had no influence on the thermal characteristics of
      the fibers produced (p > 0.05). ASBAT collagen was of higher viscosity than both
      ASRTT and PSBAT (p < 0.002), and therefore larger diameter fibers were obtained
      (p < 0.001). An inversely proportional relationship between dry-fiber diameter
      and stress at break was observed within the treatments. The PS yielded 10 times
      more soluble collagen from BAT and the derived fibers were of similar tensile
      strength, stiffness, and elongation (p > 0.05) as those derived from the AS
      collagen. No significant difference was observed for the stress at break for the
      ASBAT and the ASRTT, while significant difference was observed for the elongation
      and modulus values (p < 0.005). Overall, reconstituted collagen fibers were
      produced with properties similar to native or synthetic fibers to suit a wide
      range of tissue engineering applications.

PMID- 18041731
TI  - Bacterial adhesion and osteoblast function on titanium with surface-grafted
      chitosan and immobilized RGD peptide.
AB  - Biomaterials-associated infections remain a source of serious complications in
      modern medicine. When a biomaterial is implanted in the body, the result of
      successful tissue integration or implant infection depends on the race for the
      surface between bacteria and tissue cells. One promising strategy to reduce the
      incidence of infection is the functionalization of the biomaterial surface to
      inhibit bacterial adhesion and encourage the growth of cells. In this in vitro
      study, the surface of titanium alloy substrates was first functionalized by
      covalently grafted chitosan (CS). The cell-adhesive Arg-Gly-Asp (RGD) peptide was
      then immobilized on the CS-grafted surface through covalent binding of peptide to
      the free NH(2) groups of CS. Both these functionalized surfaces showed a decrease
      in adhesion of Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis
      (S. epidermidis) compared with the pristine substrate. A significant increase in
      osteoblast cell attachment, proliferation, and alkaline phosphatase activity was
      observed on the surface with the immobilized Arg-Gly-Asp peptide. Thus, utilizing
      surface-grafted chitosan in conjunction with the cell-adhesive peptide to modify
      the metal surface provides a promising means for enhancing tissue integration of
      implants by reducing bacterial adhesion and promoting osteoblast functions.

PMID- 18041733
TI  - A novel surface treatment for porous metallic implants that improves the rate of
      bony ongrowth.
AB  - Rapid implant fixation could prove beneficial in a host of clinical applications
      from total joint arthroplasty to trauma. We hypothesized that a novel self
      assembled monolayer of phosphonate molecules (SAMP) covalently bonded to the
      oxide surface of titanium alloy would enhance bony integration. Beaded metallic
      rods were treated with one of three coatings: SAMP, SAMP + RGD peptide, or
      hydroxyapatite. Rods were inserted retrogradely into both distal femurs of 60
      rabbits. Fifteen rabbits were sacrificed at 2, 4, 8, and 16 weeks. At each time,
      seven specimens for mechanical pull-out testing and three for histomorphometric
      analysis were available for each coating. At four weeks, both SAMP groups had
      significantly higher failure loads when compared to hydroxyapatite (p < 0.01). No
      significant differences were found among groups at other times, though the SAMP
      alone group remained stronger at 16 weeks. Histology showed abundant new bone
      formation around all the three groups, though more enhanced formation was
      apparent in the two SAMP groups. With this novel treatment, with or without RGD,
      the failure load of implants doubled in half the time as compared with
      hydroxyapatite. Where early implant fixation is important, the SAMP treatment
      provides a simple, cost-effective enhancement to bony integration of orthopaedic
      implants.

PMID- 18041732
TI  - Adhesion of MC3T3-E1 cells to bone sialoprotein and bone osteopontin specifically
      bound to collagen I.
AB  - Bone sialoprotein (BSP) and bone osteopontin (OPN) are members of the SIBLING
      (small integrin-binding ligand, N-linked glycoproteins) family of proteins
      commonly found in mineralized tissues. Previously, OPN was shown to exhibit a
      preferential orientation for MC3T3-E1 cell adhesion when it was specifically
      bound to collagen. In this work, the orientation of BSP under similar
      circumstances is examined and compared with OPN. Radiolabeled adsorption
      isotherms were obtained for BSP bound to both tissue culture polystyrene (TCPS)
      and collagen-coated TCPS. The results show that collagen has the capacity to bind
      almost twice as much OPN under identical conditions. An in vitro MC3T3-E1 cell
      adhesion assay was then performed to compare the cell binding ability of BSP on
      either TCPS or collagen-coated TCPS with identical amounts of adsorbed protein.
      It was found that there is no significant difference in the cell binding ability
      of BSP on either of the substrates. For cell binding studies on collagen-coated
      TCPS, it was shown that there are a greater number of cells bound to substrates
      with adsorbed OPN as compared with BSP. The preferable orientation of OPN for
      cell binding coupled with the higher binding capability of collagen for OPN
      indicates that OPN is more important than BSP for osteoblast adhesion to the
      collagen matrix. In addition, a cell inhibition assay was performed to show that
      all of the cell binding that occurred throughout these studies was dependent upon
      integrin interactions with the RGD cell binding moiety.

PMID- 18041734
TI  - Hydroxyapatite nanoparticle loaded collagen fiber composites: microarchitecture
      and nanoindentation study.
AB  - Hydroxyapatite (HA) nanoparticle-collagen composite materials with various
      HA/collagen weight ratios were prepared from HA/collagen dispersions using the
      solution deposition and electrospinning with static or rotating collectors. The
      composites with nanoparticle HA to collagen weight ratio of 80:20 can be easily
      prepared in the solution deposition approach, whereas in the electrospun fibrous
      composites it was possible to reach a maximum HA/collagen weight ratio of 30:70
      while maintaining a good fibrous structure. The structure, surface morphology,
      and nanoindentation properties of these nanoparticle HA/collagen composites with
      different microarchitectures were investigated. The values from 0.2 GPa to 20 GPa
      for nanoindentation Young's modulus and from 25 MPa to 500 MPa for hardness, were
      obtained depending on the fabrication technique, composition, and
      microarchitecture of the composites. It was observed that the nanoindentation
      Young's modulus and hardness of the HA/collagen composite materials seem to
      achieve maximum values for 45-60% HA content by weight.

PMID- 18041736
TI  - Pancreatic response of rats fed genetically modified soybean.
AB  - Mice fed genetically modified (GM) soybean were not affected in nutritional
      performance, but pancreatic microscopic features were disturbed. The mechanisms
      for these contradictory findings are unknown. This study analysed the histology
      of acinar pancreatic cells and the expression of pancreatitis-associated protein
      (PAP) and trypsinogen mRNA in rats fed GM soy protein. Two bioassays were run,
      each one with 34 Wistar rats distributed into two groups fed with non-GM or GM
      soy protein (18% protein) for 0, 1, 3, 5, 15 and 30 days. Nutritional evaluation,
      plasma amylase levels, pancreatic histological analysis and quantification of PAP
      and trypsinogen mRNAs levels using quantitative real-time RT-PCR were done. No
      differences in nutritional performance among rats fed non-GM and GM diets were
      found. The GM, but not the non-GM, diet induced zymogen-granule depletion after
      15 days feeding, returning to normal levels after 30 days (P < 0.05). Acinar
      disorganization started as early as 5 days after initiation of the GM diet and it
      recovered after 30 days. Levels of PAP mRNA significantly increased in the GM
      diet between day 1 and day 3 and decreased to the basal level by day 15.
      Trypsinogen mRNA peaked at two different times; at day 1 and at day 15,
      decreasing to basal levels after 30 days. Plasma amylase levels remained
      unchanged at all times. This indicates that GM soy protein intake affected
      pancreas function, evidenced by the early acute PAP mRNA increased levels and
      pancreas cellular changes followed by recuperation of acinar cells after 30 days.

PMID- 18041735
TI  - Pharmacokinetic interaction between efavirenz and dual protease inhibitors in
      healthy volunteers.
AB  - The combination of efavirenz with HIV-1 protease inhibitors (PI) results in
      complex interactions secondary to mixed induction and inhibition of oxidative
      metabolism. ACTG A5043 was a prospective, open-label, controlled, two-period,
      multiple-dose study with 55 healthy volunteers. The objective of the present
      study was to evaluate the potential pharmacokinetic interaction between efavirenz
      and dual PIs. The subjects received a daily dose of 600 mg efavirenz for 10 days
      with amprenavir 600 mg twice daily added at day 11 and were randomized to receive
      nelfinavir, indinavir, ritonavir, saquinavir, or no second PI on days 15-21.
      Intensive pharmacokinetic studies were conducted on day 14 and 21. Efavirenz
      plasma concentrations were fit to candidate models using weighted non-linear
      regression. The disposition of efavirenz was described by a linear two
      compartment model with first order absorption following a fitted lag time.
      Apparent clearance (CLt/F), volume of distribution at steady state (Vss/F), inter
      compartmental clearance, and the central and peripheral volume of distribution
      were estimated. The mean CLt/F and Vss/F of efavirenz were 0.126 l/h/kg and 4.412
      l/kg, respectively. Both AUC and CLt/F of efavirenz remained unchanged after 7
      days of dual PI dosing. The mean Vss/F of efavirenz increased an average of 89%
      across arms, ranging from 52% (nelfinavir) to 115% (indinavir) relative to
      efavirenz with amprenavir alone. Increases were also observed in Vp/F after the
      addition of nelfinavir, indinavir, ritonavir and saquinavir by 85%, 170%, 162%
      and 111%, respectively. In conclusion, concomitant administration of dual PIs is
      unlikely to have any clinically significant effect on the pharmacokinetics of
      CYP2B6 substrates in general or oral efavirenz specifically.

PMID- 18041737
TI  - Structural and functional MRI correlates of Stroop control in benign MS.
AB  - The objective of this study was to assess the functional and structural
      substrates of cognitive network changes in patients with benign multiple
      sclerosis (BMS), using an analysis of effective connectivity and MR tractography.
      Using a 3-Tesla scanner, we acquired dual-echo, diffusion tensor (DT) and
      functional MRI during the performance of the Stroop task from 15 BMS patients and
      19 healthy controls. DT MRI tractography was used to calculate DT derived metrics
      from several white matter (WM) fiber bundles, thought to be involved in cognitive
      performance. DT MRI metrics from WM fiber bundles not directly related with
      cognitive performance were also derived. Effective connectivity analysis was
      performed using statistical parametric mapping. MS patients had significantly
      abnormal DT MRI metrics in all the structures analyzed. Compared with controls,
      MS patients had more significant activations of several areas of the cognitive
      network involved in Stroop performance, bilaterally. Compared with controls, BMS
      patients also had increased connectivity strengths between several cortical areas
      of the sensorimotor network and the right (R) inferior frontal gyrus and the R
      cerebellum, as well as decreased connectivity strengths with the anterior
      cingulate cortex. Coefficients of altered connectivity were moderately correlated
      with structural MRI metrics of tissue damage within intra- and inter-hemispheric
      cognitive-related WM fiber bundles, while no correlations were found with the
      remaining fiber bundles studied, suggesting that functional cortical changes in
      patients with BMS might represent an adaptive response driven by damage of
      specific WM structures.

PMID- 18041738
TI  - Model-free group analysis shows altered BOLD FMRI networks in dementia.
AB  - FMRI research in Alzheimer's disease (AD) and mild cognitive impairment (MCI)
      typically is aimed at determining regional changes in brain function, most
      commonly by creating a model of the expected BOLD-response and estimating its
      magnitude using a general linear model (GLM) analysis. This crucially depends on
      the suitability of the temporal assumptions of the model and on assumptions about
      normality of group distributions. Exploratory data analysis techniques such as
      independent component analysis (ICA) do not depend on these assumptions and are
      able to detect unknown, yet structured spatiotemporal processes in neuroimaging
      data. Tensorial probabilistic ICA (T-PICA) is a model free technique that can be
      used for analyzing multiple subjects and groups, extracting signals of interest
      (components) in the spatial, temporal, and also subject domain of FMRI data. We
      applied T-PICA and model-based GLM to study FMRI signal during face encoding in
      18 AD, 28 MCI patients, and 41 healthy elderly controls. T-PICA showed activation
      in regions associated with motor, visual, and cognitive processing, and
      deactivation in the default mode network. Six networks showed a significantly
      decreased response in patients. For two networks the T-PICA technique was
      significantly more sensitive to detect group differences than the standard model
      based technique. We conclude that T-PICA is a promising tool to identify and
      detect differences in (de)activated brain networks in elderly controls and
      dementia patients. The technique is more sensitive than the commonly applied
      model-based method. Consistent with other research, we show that networks of
      activation and deactivation show decreased reactivity in dementia.

PMID- 18041739
TI  - Tactile-associated fMRI recruitment of the cervical cord in healthy subjects.
AB  - Using spinal cord functional magnetic resonance imaging (fMRI), 12 right-handed
      healthy subjects were scanned during a tactile stimulation of the palm of the
      right hand. The task-related mean signal change was computed for all activated
      voxels within the cervical cord, and separately, in the four cord quadrants
      (right and left anterior, right and left posterior) from C5 to C8. The frequency
      of fMRI activity at each cord level was obtained by assigning a score of 25% at
      each active quadrant and by averaging the percentage of active quadrants at each
      level of all subjects. The difference in the occurrence of fMRI activity (a) in
      right versus left, and anterior versus posterior cord, and (b) among the
      different cord levels, was evaluated using a random effect logistic regression
      model, with the frequency of fMRI activity as the dependent variable and the
      subject as the grouping factor. The task-related mean signal change of all
      activated voxels of the cord was 3.2% (SD = 0.8%). During the tactile
      stimulation, subjects showed a higher occurrence of fMRI cord activity in the
      right than in the left cervical cord (odds ratio = 2.25, 95% confidence interval
      = 1.31-3.87, P = 0.003). A significant heterogeneity in frequency of fMRI
      activity between cord levels was also observed (P < 0.001), with the highest
      frequencies of fMRI activity detected at C6 and C7. Spinal cord fMRI enables to
      obtain reliable physiological information on the activity of human spinal
      circuits associated to tactile stimulation. This holds significant promise for a
      better planning and conduct of studies of people with diseased spinal cords.

PMID- 18041740
TI  - Stimulus-contrast-induced biases in activation order reveal interaction between
      V1/V2 and human MT+.
AB  - The luminance contrast of a visual stimulus is known to modulate the response
      properties of areas V1 and the human MT complex (hMT+), but has not been shown to
      modulate interactions between these two areas. We examined the direction of
      information transfer between V1/V2 and hMT+ at different stimulus contrasts by
      measuring magnetoencephalographic (MEG) responses to moving and stationary
      stimuli presented centrally or peripherally. To determine the direction of
      information flow, the different response latencies among stimuli and hemispheres
      in V1/V2 was compared with those of hMT+. At high contrast, responses to stimulus
      motion and position began in V1/V2, and were followed in hMT+ with a delay
      between 34 and 55 ms. However, at low contrast, lateralized responses in hMT+
      came first, with those in V1/V2 lagging with a delay of 27 ms. Also, at high
      contrast, stationary stimuli produced greater responses than motion stimuli in
      V1/V2, while the reverse was true in hMT+, whose response lagged behind the
      initial response in V1/V2. The same activation order was found using Mutual
      Information Analysis of the response variances for each condition. Here, the
      response variances in hMT+ mimicked and trailed those of V1/V2 at high contrast,
      whereas the reverse was true at low contrast. Such consistent interactions found
      using two different methodologies strongly supports a processing link between
      these two areas. The results also suggest that feedback from hMT+ for low
      contrast stimuli compensates for unresolved processing in V1/V2 when the input of
      a visual image is weak.

PMID- 18041741
TI  - Differences in genetic and environmental influences on the human cerebral cortex
      associated with development during childhood and adolescence.
AB  - In this report, we present the first regional quantitative analysis of age
      related differences in the heritability of cortical thickness using anatomic MRI
      with a large pediatric sample of twins, twin siblings, and singletons (n = 600,
      mean age 11.1 years, range 5-19). Regions of primary sensory and motor cortex,
      which develop earlier, both phylogenetically and ontologically, show relatively
      greater genetic effects earlier in childhood. Later developing regions within the
      dorsal prefrontal cortex and temporal lobes conversely show increasingly
      prominent genetic effects with maturation. The observation that regions
      associated with complex cognitive processes such as language, tool use, and
      executive function are more heritable in adolescents than children is consistent
      with previous studies showing that IQ becomes increasingly heritable with
      maturity(Plomin et al. 1997: Psychol Sci 8:442-447). These results suggest that
      both the specific cortical region and the age of the population should be taken
      into account when using cortical thickness as an intermediate phenotype to link
      genes, environment, and behavior.

PMID- 18041742
TI  - Distinct expression patterns of the immunogenic differentiation antigen NY-BR-1
      in normal breast, testis and their malignant counterparts.
AB  - NY-BR-1 is a differentiation antigen and a potential target for cancer
      immunotherapy. Its mRNA expression is restricted to breast, testis, prostate and
      breast cancer by RT-PCR. In this study, we correlated NY-BR-1 protein and mRNA
      expression on tissue microarrays of mammary, prostatic and testicular
      malignancies using immunohistochemistry and in situ hybridization with probes for
      exon 4-7 and 30-33. NY-BR-1 mRNA was confined to primary spermatocytes,
      suggesting a role in spermatogenesis. Exon 4-7 and 30-33 were equally expressed
      this cell type. However, NY-BR-1 was absent in all germ cell tumours analyzed (n
      = 475) and present in one of 56 (2%) prostate carcinomas. In breast, NY-BR-1 mRNA
      expression was detected in 307 of 442 (70%) primary carcinomas, with strong
      correlation to its protein expression (p < 0.0001). mRNA expression was
      significantly stronger and more frequently detected by the exon 30-33 probe than
      by the exon 4-7 probe (70% vs. 35%, p < 0.0001), indicating the presence of
      alternative splice variants that lack 5-prime sequences. A similar restricted
      mRNA pattern was also observed in the normal breast epithelium. NY-BR-1 protein
      and mRNA correlated significantly with estrogen receptor alpha (ER alpha) protein
      expression (p < 0.0001), with stronger association to NY-BR-1 mRNA than protein
      (odds ratio 7.7 compared to 4.6). We identified 4 estrogen response elements
      (ERE)-like sequences nearby the promoter region, suggesting that NY-BR-1
      transcription might be controlled by ER alpha. Accordingly, analysis of matching
      pairs of primary tumors with their recurrences showed a marked decrease of NY-BR
      1 expression in recurrences after tamoxifen treatment (p < 0.0001).

PMID- 18041743
TI  - STN-stimulation in Parkinson's disease restores striatal inhibition of
      thalamocortical projection.
AB  - To test the hypothesis that deep brain stimulation of the subthalamic nucleus
      (STN) restores the inhibitory output to the striatothalamocortical loop in
      Parkinson's disease, we obtained functional brain images of blood flow in 10 STN
      stimulated patients with Parkinson's disease. Patients were immobile and off
      antiparkinsonian medication for 12 h. They were scanned with and without
      bilateral STN-stimulation with a 4-h interval between the two conditions. The
      order of DBS stimulation (ON or OFF) was randomized. Stimulation significantly
      raised regional cerebral blood flow (rCBF) bilaterally in the STN and in the left
      nucleus lentiformis. Conversely, flow declined in the left supplementary motor
      area (BA 6), ventrolateral nucleus of the left thalamus, and right cerebellum.
      Activation of the basal ganglia and deactivation of supplementary motor area and
      thalamus were both correlated with the improvement of motor function. The result
      is consistent with the explanation that stimulation in resting patients raises
      output from the STN with activation of the inhibitory basal ganglia output nuclei
      and subsequent deactivation of the thalamic anteroventral and ventrolateral
      nuclei and the supplementary motor area.

PMID- 18041744
TI  - Activation of mitogen activated protein kinase (MAPK) pathways after soman
      poisoning in rat cerebellar granule neurons.
AB  - The expression of activated p38 mitogen-activated protein kinase (MAPK) and
      activated MAPK transcription factors c-jun, c-myc and elk-1 were examined in rat
      cerebellum after soman poisoning to determine the pathogenetic mechanism of the
      non-specific long-term effects of nerve agents. Male Wistar rats were poisoned by
      intramuscular administration of soman at a dose 60 microg kg(-1) (70% LD(50)) and
      samples were taken 1, 7 and 14 days after poisoning, immunohistochemically
      stained and p-p38MAPK, p-c-jun, p-c-myc and p-elk-1 expressions were measured
      using image analysis. Control groups were administered with saline instead of
      soman. The expression of activated p38MAPK and c-myc increased 14 days after
      soman poisoning while c-jun and elk-1 expressions remained unchanged 1, 7 and 14
      days after soman poisoning. Delayed activation of p38 MAPK and its targets might
      be involved in the pathogenetic mechanism of the long-term neurophysiological
      toxic effects of nerve agents.

PMID- 18041745
TI  - Bmi-1 expression predicts prognosis for patients with gastric carcinoma.
AB  - BACKGROUND AND OBJECTIVE: The Bmi-1 gene is a transcriptional repressor involved
      in oncogenesis in various human cancers. Here, we examine Bmi-1 expression in
      gastric carcinoma (GC) and investigates whether its expression correlates with
      patient prognosis. METHODS: Immunohistochemistry was performed using an anti-Bmi
      1 antibody on primary tumor samples of 146 cases of GC. The association between
      Bmi-1 expression and the clinicopathological status and prognosis of GC patients
      was statistically analyzed. Furthermore, reverse transcription-PCR (RT-PCR) and
      Western blotting were performed to determine the expression levels of Bmi-1 in an
      additional 8 GC and the adjacent non-cancerous samples. RESULTS: Using
      immunohistochemistry, we found that 99 of 146 paraffin-embedded GC samples
      expressed Bmi-1 extensively. Statistical analysis showed that Bmi-1
      overexpression was highly correlated with tumor size, clinical stage, lymph node
      metastasis and T classification (P < 0.05), Patients with Bmi-1 expression had
      shorter overall survival time than those without Bmi-1 expression (P < 0.01).
      Multivariate analysis indicated that Bmi-1 expression is an independent
      prognostic factor of GC. RT-PCR and Western blotting showed that Bmi-1 was up
      regulated at both the transcriptional and translational levels in the GC tissues
      compared with the adjacent non-cancerous tissues. CONCLUSIONS: Bmi-1 may serve as
      a valuable marker for diagnosis and prognosis of GC.

PMID- 18041746
TI  - Liver resection for metastases from breast cancer.
AB  - BACKGROUND AND OBJECTIVES: The value of liver resection for metastases from
      breast cancer is still controversial. This study was conducted to clarify safety
      and effectiveness of hepatectomy in this conditions and to identify selection
      criteria for patients suitable for liver resection. METHODS: From January 1988 to
      December 2006, 39 patients underwent liver resection for metastases from breast
      cancer. The outcome of these 39 patients was retrospectively reviewed using a
      prospective database. Prognostic factors for patient survival were determined by
      univariate and multivariate analysis. RESULTS: None of the patients died
      perioperatively and the morbidity rate was 13% (n = 5). The overall 1-, 3-, and 5
      year survival rates were 77%, 50%, and 42%, respectively. In the univariate
      analysis, metastatic manifestation prior to hepatectomy, vascular invasion and
      resection margin revealed statistically significant influence on survival. The
      multivariate analysis identified only resection margin as an independent
      prognostic factor for survival. CONCLUSIONS: Liver resection should be considered
      in the multimodal treatment approach of patients with metastatic breast cancer.
      Hepatic resection can be performed with low risk and offers a chance of long-term
      survival. Achievement of a curative resection and less important absence of
      previous metastatic manifestation represent suitable criteria to select patients
      for liver resection.

PMID- 18041747
TI  - Detection and characterization of vascular endothelial growth factors and their
      receptors in a series of angiosarcomas.
AB  - BACKGROUND: Angiosarcomas are malignant mesenchymal neoplasms, including sarcomas
      of presumptive vascular endothelial origin and sarcomas of probable lymphatic
      origin. It is, however, often difficult to determine whether they are from blood
      vascular or lymphatic endothelium. The majority of angiosarcomas are thought to
      originate from vascular endothelia and spread via bloodstream to lung, but
      lymphatic metastases can occur. METHODS: We investigated immunohistochemical
      expression of vascular endothelial growth factors (VEGF-A, VEGF-C) and their
      receptors (VEGFR-1, VEGFR-2, VEGFR-3) in a series of 34 angiosarcomas. RESULTS:
      VEGF-A was expressed by 32/34 (94%), VEGF-C by 4/34 (12%), VEGFR-1 by 32/34
      (94%), VEGFR-2 by 22/34 (65%), and VEGFR-3 by 27/34 (79%). Patients who expressed
      low or no VEGFR-2 showed a significantly unfavorable prognosis by log-rank test
      (P = 0.010) and multivariate analysis (hazard ratio, 5.16; 95% CI, 1.40-19.04; P
      = 0.014). VEGFR-1 and VEGFR-3 were not significantly associated with patients'
      prognosis. CONCLUSIONS: VEGF-A and VEGFR-1 were detected in diverse subtypes of
      angiosarcomas. In cooperation, VEGF-A and VEGF-C are likely to be involved in the
      development of angiosarcoma associated with lymphedema. VEGF-C expression may
      cause susceptibility to lymphatic metastasis through tumor lymphangiogenesis.
      Angiosarcoma of the scalp, which is traditionally considered as a true
      hemangiosarcoma, may include some cases of lymphatic origin.

PMID- 18041748
TI  - Large scale analysis of protein-binding cavities using self-organizing maps and
      wavelet-based surface patches to describe functional properties, selectivity
      discrimination, and putative cross-reactivity.
AB  - A new method to discover similar substructures in protein binding pockets,
      independently of sequence and folding patterns or secondary structure elements,
      is introduced. The solvent-accessible surface of a binding pocket, automatically
      detected as a depression on the protein surface, is divided into a set of surface
      patches. Each surface patch is characterized by its shape as well as by its
      physicochemical characteristics. Wavelets defined on surfaces are used for the
      description of the shape, as they have the great advantage of allowing a
      comparison at different resolutions. The number of coefficients to describe the
      wavelets can be chosen with respect to the size of the considered data set. The
      physicochemical characteristics of the patches are described by the assignment of
      the exposed amino acid residues to one or more of five different properties
      determinant for molecular recognition. A self-organizing neural network is used
      to project the high-dimensional feature vectors onto a two-dimensional layer of
      neurons, called a map. To find similarities between the binding pockets, in both
      geometrical and physicochemical features, a clustering of the projected feature
      vector is performed using an automatic distance- and density-based clustering
      algorithm. The method was validated with a small training data set of 109 binding
      cavities originating from a set of enzymes covering 12 different EC numbers. A
      second test data set of 1378 binding cavities, extracted from enzymes of 13
      different EC numbers, was then used to prove the discriminating power of the
      algorithm and to demonstrate its applicability to large scale analyses. In all
      cases, members of the data set with the same EC number were placed into coherent
      regions on the map, with small distances between them. Different EC numbers are
      separated by large distances between the feature vectors. A third data set
      comprising three subfamilies of endopeptidases is used to demonstrate the ability
      of the algorithm to detect similar substructures between functionally related
      active sites. The algorithm can also be used to predict the function of novel
      proteins not considered in training data set.

PMID- 18041749
TI  - Intubation secondary to asthma exacerbation in a patient with asthma receiving
      Xolair (omalizumab).

PMID- 18041750
TI  - Differential effects of chronic intermittent and chronic constant hypoxia on
      postnatal growth and development.
AB  - Exposure to chronic constant or intermittent hypoxia (CCH or CIH) may have
      different effects on growth and development in early life. In this work, we
      exposed postnatal day 2 (P2) CD1 mice to CCH or CIH (11% O2) for 4 weeks and
      examined the effect of hypoxia on body and organ growth until P30. Regression
      analysis showed that weight increased in control, CCH and CIH cohorts with age
      with r2 values of 0.99, 0.97, and 0.94, respectively. Between days 2 and 30,
      slopes were 0.93+/-0.057, 0.76+/-0.108, and 0.63+/-0.061 (g/day, means+/-SEM) for
      control, CIH, and CCH, respectively and significantly different from each other
      (P<0.001). The slopes between P2 and P16 were 0.78+/-0.012, 0.46+/-0.002, and
      0.47+/-0.019 for control, CCH and CIH, respectively. From P16 to 30, slopes were
      1.12+/-0.033, 1.09+/-0.143, and 0.82+/-0.08 for control, CIH, and CCH,
      respectively with no significant difference from each other, suggesting a catch
      up growth in the latter part of the hypoxic period. Slower weight gain resulted
      in a 12% and 23% lower body weight in CIH and CCH mice (P<0.001) by P30.
      Lung/body ratios were 0.010, 0.015, 0.015 for control, CIH, and CCH at P30,
      respectively. The decrease in liver, kidney, and brain weight were greater in CCH
      than CIH. Smaller liver weight was shown to be due to a reduction in cell size
      and cell number. Liver in CIH and CCH mice showed a 5% and 10% reduction in cell
      size (P<0.05) and a reduction of 28% in cell number (P<0.001) at P30. In
      contrast, CCH and CIH heart weight was 13% and 33% greater than control at P30
      (P<0.05), respectively. This increase in the heart weight was due to an increase
      in the size of cardiomyocytes which showed an increase of 12% and 14% (P<0.001)
      for CIH and CCH, respectively as compared to control. Brain weight was 0.48 and
      0.46 g for CIH and CCH, respectively (95% and 92% of normal). We concluded that
      (a) CIH and CCH follow different body and organ growth patterns; (b) mostly with
      CCH, the liver and kidneys are reduced in size in a proportionate way to body
      size but heart, lung, and brain are either spared or increased in size compared
      to body weight; and (c) the decrease in liver is secondary mostly to a decrease
      in cell number.

PMID- 18041751
TI  - C-reactive protein in children with obstructive sleep apnea and the effects of
      treatment.
AB  - OBJECTIVE: To evaluate C-reactive protein (CRP) concentration in children with
      OSA and to determine the effects of treatment for OSA on its serum concentration.
      METHODS: Consecutive children with habitual snoring and symptoms suggestive of
      OSA were recruited. They completed a sleep apnea symptom questionnaire, underwent
      physical examination and an overnight polysomnography (PSG). Fasting serum CRP
      and lipid profile were taken after overnight PSG. OSA was diagnosed if
      obstructive apnea index (OAI)>1. RESULTS: One hundred forty-one children with a
      median (IQR) age of 10.8 (8.5-12.8) years were recruited. There were 96 boys and
      the commonest presenting symptoms were nocturnal mouth breathing, prone sleeping
      position and poor attention at school. Forty-five children were found to have OSA
      and those with moderate disease (OAI>5) had significantly higher CRP levels
      compared to their non-OSA counterparts [1.3 (0.8-3.6) vs. 0.7 (0.2-2.0), P=0.01].
      Stepwise linear multiple regression analysis indicated that OAI was independently
      associated with CRP (beta coefficient=0.013, P=0.001). Sixteen children underwent
      treatment and there was significant reduction in their serum CRP after
      intervention [pre vs. post-CRP, 1.3 (0.6-4.1) vs. 0.4 (0.2-1.3), P=0.033]. A
      significant correlation was also demonstrated between change in CRP and change in
      OAI (r=0.593, P=0.042) following treatment for OSA. CONCLUSION: Children with OSA
      may have associated systemic inflammation as reflected by a raised CRP that
      decreased significantly following treatment.

PMID- 18041752
TI  - Non-invasive ventilation reduces respiratory tract infections in children with
      neuromuscular disorders.
AB  - Non-invasive ventilation (NIV) has been shown to improve gas exchange and
      survival in patients with chronic neuromuscular disorders. Little is known about
      its influence on respiratory tract infections (RTIs). Twenty-four patients with
      regular use of NIV and 11 patients without NIV with neuromuscular disorders
      answered a questionnaire concerning the use of NIV and assisted coughing
      techniques, the status of influenza and pneumococcus vaccination, and the
      frequency and severity of RTIs. Additionally, we performed a retrospective chart
      review of twelve patients who were ventilated over a period of at least 5 years.
      In the first year of NIV consultations of a general practitioner due to RTI
      decreased from 9.2+/-20.8 to 3.2+/-5.3 per year (P<0.005), the number of
      antibiotic treatment due to RTI decreased from 4.1+/-3.4 to 1.9+/-2.2 per year
      (P<0.005) and the number of hospital admissions due to RTI decreased from 1.6+/
      1.7 to 0.7+/-1.3 per year (P<0.005). Vaccinations against influenza and/or
      pneumococcus did not have a significant influence on the rate of infections. In
      12 patients using NIV for more than 5 years the incidence of RTI requiring
      hospital admission decreased from 0.54+/-0.41/year in the pre-ventilation period
      to 0.12+/-0.09/year in the NIV period (P<0.005). NIV had a favorable impact on
      respiratory infectious complications in children with neuromuscular disorders.

PMID- 18041753
TI  - An experimental model for the measurement of inspired gas temperatures in
      ventilated neonates.
AB  - OBJECTIVE: To determine the inspired gas temperature at points from the endo
      tracheal tube (ETT) circuit manifold to the tip of the ETT in a model neonatal
      lung. DESIGN: A model lung attached to standard ventilator circuit, autofeed
      chamber and humidifier was ventilated using typical pressure-limited, time cycled
      settings. Temperatures were measured at various distances along the ETT using a K
      type thermocouple temperature probe. RESULTS: The inspired gas temperature
      dropped from the circuit temperature probe site (40 degrees C) to the proximal
      end of the ETT (37 degrees C). The temperature dropped further as it passed
      through the exposed part of the ETT (34 degrees C) but then warmed again on
      entering the lung model so that the inspired gas at the distal end of the ETT was
      37 degrees C. Statistically significant differences were found with a one-way
      ANOVA P-value of <0.0001. The differences between each pair of mean temperatures
      were statistically significant (all P<0.001) except when comparing the proximal
      end of the ETT with midway down the ETT (Bonferroni's Multiple Comparison Test,
      P>0.05). CONCLUSIONS: Inspired gas temperature drops as it passes through the
      circuit temperature probe site, the proximal end of the ETT and the exposed part
      of the ETT. The inspired gas rewarms on entering the model lung and exits the ETT
      at the desired temperature. The effect of measuring temperature closer to the
      patient, setting the circuit temperature higher and/or increasing the ambient
      temperature through which the circuit passes, need to be evaluated.

PMID- 18041754
TI  - Spontaneous pneumothorax in children: when is invasive treatment indicated?
AB  - A retrospective review of pneumothoraces in children presenting to a major
      tertiary children's hospital is described. A total of 35 cases in 31 patients of
      spontaneous pneumothorax were identified over a 10-year period. There was one
      case of bilateral pneumothorax and three cases of recurrent pneumothoraces.
      Twenty-four cases (69%) required intercostal tube catheter drainage for a mean of
      4.9 days (range 2-10 days). Eleven cases, including two cases in CF patients, and
      three cases in patients with Marfan's Syndrome proceeded to a secondary surgical
      procedure after a continuing air leak was present for an average of 5.9 days
      (range 2-16 days). In follow-up studies on 11 cases, 5 (45%) were found to have
      apical abnormalities of the lung on CT scanning. Pneumothoraces were identified
      in six cases of patients with cystic fibrosis as well as four in patients with
      Marfan's Syndrome. This present study has suggested that unless intercostal
      catheter treatment resolves the air leak associated with a spontaneous
      pneumothorax within 5 days that surgical intervention is most likely to be
      required to achieve a full resolution.

PMID- 18041755
TI  - Pulmonary function in adolescents with ataxia telangiectasia.
AB  - INTRODUCTION: Pulmonary complications are common in adolescents with ataxia
      telangiectasia (A-T), however objective measurements of lung function may be
      difficult to obtain because of underlying bulbar weakness, tremors, and
      difficulty coordinating voluntary respiratory maneuvers. To increase the
      reliability of pulmonary testing, minor adjustments were made to stabilize the
      head and to minimize leaks in the system. Fifteen A-T adolescents completed lung
      volume measurements by helium dilution. To assess for reproducibility of
      spirometry testing, 10 A-T adolescents performed spirometry on three separate
      occasions. RESULTS: Total lung capacity (TLC) was normal or just mildly decreased
      in 12/15 adolescents tested. TLC correlated positively with functional residual
      capacity (FRC), a measurement independent of patient effort (R2=0.71). The
      majority of individuals had residual volumes (RV) greater than 120% predicted
      (10/15) and slow vital capacities (VC) less than 70% predicted (9/15). By
      spirometry, force vital capacity (FVC) and forced expiratory volume in 1 sec
      (FEV1) values were reproducible in the 10 individuals who underwent testing on
      three separate occasions (R=0.97 and 0.96 respectively). Seven of the 10
      adolescents had FEV1/FVC ratios>90%. CONCLUSION: Lung volume measurements from A
      T adolescents revealed near normal TLC values with increased RV and decreased VC
      values. These findings indicate a decreased ability to expire to residual volume
      rather then a restrictive defect. Spirometry was also found to be reproducible in
      A-T adolescents suggesting that spirometry testing may be useful for tracking
      changes in pulmonary function over time in this population.

PMID- 18041756
TI  - Congenital central hypoventilation syndrome: PHOX2B genotype determines risk for
      sudden death.
AB  - OBJECTIVE: Children with Congenital Central Hypoventilation Syndrome (CCHS) have
      cardiovascular symptoms consistent with the autonomic nervous system
      dysregulation/dysfunction (ANSD) phenotype. We hypothesized that children with
      CCHS would have a relationship between PHOX2B genotype and two clinically
      applicable cardiovascular measures of ANSD: duration of longest r-r interval and
      longest corrected QT interval (QTc). MATERIALS AND METHODS: We studied 501 days
      of Holter recordings from 39 individuals with PHOX2B mutation-confirmed CCHS, and
      analyzed longest r-r and QTc intervals with respect to PHOX2B genotype. RESULTS:
      We determined that longest r-r interval varied by genotype (P=0.001), with a
      positive correlation between repeat number and longest r-r interval duration
      (P=0.0007). Number of children with a longest r-r interval value>or=3 sec varied
      by genotype (P<0.0001): 0% with the 20/25 genotype, 19% with the 20/26 genotype,
      and 83% with the 20/27 genotype. Though longest QTc interval did not vary by
      genotype (P=0.09), all children with CCHS had at least one Holter with a QTc
      interval>450 msec, and percent of time with QTc>450 msec exceeded published
      values. The proportion of subjects who received a cardiac pacemaker due to
      prolonged r-r interval was greater for the children with the 20/27 genotype (67%)
      than the 20/25 (0%) or 20/26 genotype (25%) (P=0.01). Among three children who
      did not receive a cardiac pacemaker, but who had r-r intervals>or=3 sec, two died
      suddenly. CONCLUSIONS: These results confirm a disturbance of cardiac autonomic
      regulation in CCHS, indicate that PHOX2B genotype is related to the severity of
      dysregulation, predict the need for cardiac pacemaker, and offer the clinician
      the potential to avert sudden death.

PMID- 18041757
TI  - Percutaneous penetration and absorption of parathion using human and pig skin
      models in vitro and human skin grafted onto nude mouse skin model in vivo.
AB  - This study determined and compared the percutaneous penetration and absorption of
      an organophosphorus (OP) pesticide, parathion (PA), using three experimental skin
      models: namely the human abdominal- and pig-ear skin in vitro models and the
      Human Skin grafted onto a nude mouse (HuSki) in vivo model. The percentage of
      topically applied dose absorbed and the doses present in the stratum corneum and
      skin were systematically determined at 24 h under similar experimental
      conditions. The three experimental skin models were first compared. Then, the
      advantages of the HuSki model for in vivo PA skin absorption studies were
      evaluated compared with the pig in vivo model previously used by others. Lastly,
      the relevance of each skin model to predict the permeability of human skin to PA
      in vivo was assessed by comparing our results with previously published in vivo
      human volunteer values. It was demonstrated that (a) pig-ear skin is relevant for
      predicting the in vitro human abdominal skin absorption taking into account a 2-3
      times higher skin permeability to PA, (b) using ethanol as the vehicle, the
      absorption of PA was 4-5 times higher in the HuSki model than in the pig model
      but supports the usefulness of the HuSki model to easy mass balance studies, (c)
      both human in vitro and HuSki models closely predict the in vivo human volunteer
      absorption at 24 h when acetone is used as a vehicle but the HuSki model
      overcomes the known limitations of in vitro models for studying the fate of PA in
      the different skin layers after topical application.

PMID- 18041758
TI  - Crystallographic and computational studies on 4-phenyl-N-(beta-D-glucopyranosyl)
      1H-1,2,3-triazole-1-acetamide, an inhibitor of glycogen phosphorylase: comparison
      with alpha-D-glucose, N-acetyl-beta-D-glucopyranosylamine and N-benzoyl-N'-beta-D
      glucopyranosyl urea binding.
AB  - 4-Phenyl-N-(beta-D-glucopyranosyl)-1H-1,2,3-triazole-1-acetamide
      (glucosyltriazolylacetamide) has been studied in kinetic and crystallographic
      experiments with glycogen phosphorylase b (GPb), in an effort to utilize its
      potential as a lead for the design of potent antihyperglycaemic agents. Docking
      and molecular dynamics (MD) calculations have been used to monitor more closely
      the binding modes in operation and compare the results with experiment. Kinetic
      experiments in the direction of glycogen synthesis showed that
      glucosyltriazolylacetamide is a better inhibitor (K(i) = 0.18 mM) than the parent
      compound alpha-D-glucose (K(i) = 1.7 mM) or beta-D-glucose (K(i) = 7.4 mM) but
      less potent inhibitor than the lead compound N-acetyl-beta-D-glucopyranosylamine
      (K(i) = 32 microM). To elucidate the molecular basis underlying the inhibition of
      the newly identified compound, we determined the structure of GPb in complex with
      glucosyltriazolylacetamide at 100 K to 1.88 A resolution, and the structure of
      the compound in the free form. Glucosyltriazolylacetamide is accommodated in the
      catalytic site of the enzyme and the glucopyranose interacts in a manner similar
      to that observed in the GPb-alpha-D-glucose complex, while the substituent group
      in the beta-position of the C1 atom makes additional hydrogen bonding and van der
      Waals interactions to the protein. A bifurcated donor type hydrogen bonding
      involving O3H, N3, and N4 is seen as an important structural motif strengthening
      the binding of glucosyltriazolylacetamide with GP which necessitated change in
      the torsion about C8-N2 bond by about 62 degrees going from its free to the
      complex form with GPb. On binding to GP, glucosyltriazolylacetamide induces
      significant conformational changes in the vicinity of this site. Specifically,
      the 280s loop (residues 282-288) shifts 0.7 to 3.1 A (CA atoms) to accommodate
      glucosyltriazolylacetamide. These conformational changes do not lead to increased
      contacts between the inhibitor and the protein that would improve ligand binding
      compared with the lead compound. In the molecular modeling calculations, the GOLD
      docking runs with and without the crystallographic ordered cavity waters using
      the GoldScore scoring function, and without cavity waters using the ChemScore
      scoring function successfully reproduced the crystallographic binding
      conformation. However, the GLIDE docking calculations both with (GLIDE XP) and
      without (GLIDE SP and XP) the cavity water molecules were, impressively, further
      able to accurately reproduce the finer details of the GPb
      glucosyltriazolylacetamide complex structure. The importance of cavity waters in
      flexible receptor MD calculations compared to "rigid" (docking) is analyzed and
      highlighted, while in the MD itself very little conformational flexibility of the
      glucosyltriazolylacetamide ligand was observed over the time scale of the
      simulations.

PMID- 18041759
TI  - Modeling of metal interaction geometries for protein-ligand docking.
AB  - The accurate modeling of metal coordination geometries plays an important role
      for structure-based drug design applied to metalloenzymes. For the development of
      a new metal interaction model, we perform a statistical analysis of metal
      interaction geometries that are relevant to protein-ligand complexes. A total of
      43,061 metal sites of the Protein Data Bank (PDB), containing amongst others
      magnesium, calcium, zinc, iron, manganese, copper, cadmium, cobalt, and nickel,
      were evaluated according to their metal coordination geometry. Based on
      statistical analysis, we derived a model for the automatic calculation and
      definition of metal interaction geometries for the purpose of molecular docking
      analyses. It includes the identification of the metal-coordinating ligands, the
      calculation of the coordination geometry and the superposition of ideal polyhedra
      to identify the optimal positions for free coordination sites. The new
      interaction model was integrated in the docking software FlexX and evaluated on a
      data set of 103 metalloprotein-ligand complexes, which were extracted from the
      PDB. In a first step, the quality of the automatic calculation of the metal
      coordination geometry was analyzed. In 74% of the cases, the correct prediction
      of the coordination geometry could be determined on the basis of the protein
      structure alone. Secondly, the new metal interaction model was tested in terms of
      predicting protein-ligand complexes. In the majority of test cases, the new
      interaction model resulted in an improved docking accuracy of the top ranking
      placements.

PMID- 18041760
TI  - Stabilization of antibody structure upon association to a human carbonic
      anhydrase IX epitope studied by X-ray crystallography, microcalorimetry, and
      molecular dynamics simulations.
AB  - Specific antibodies interfere with the function of human tumor-associated
      carbonic anhydrase IX (CA IX), and show potential as tools for anticancer
      interventions. In this work, a correlation between structural elements and
      thermodynamic parameters of the association of antibody fragment Fab M75 to a
      peptide corresponding to its epitope in the proteoglycan-like domain of CA IX, is
      presented. Comparisons of the crystal structures of free Fab M75 and its complex
      with the epitope peptide reveal major readjustments of CDR-H1 and CDR-H3. In
      contrast, the overall conformations and positions of CDR-H2 and CDR-L2 remain
      unaltered, and their positively charged residues may thus present a fixed frame
      for epitope recognition. Adoption of the altered CDR-H3 conformation in the
      structure of the complex is accompanied by an apparent local stabilization.
      Analysis of domain mobility with translation-libration-screw (TLS) method shows
      that librations of the entire heavy chain variable domain (V(H)) decrease and
      reorient in the complex, which correlates well with participation of the heavy
      chain in ligand binding. Isothermal titration microcalorimetry (ITC) experiments
      revealed a highly unfavorable entropy term, which can be attributed mainly to the
      decrease in the degrees of freedom of the system, the loss of conformational
      freedom of peptide and partially to a local stabilization of CDR-H3. Moreover, it
      was observed that one proton is transferred from the environment to the protein
      ligand complex upon binding. Molecular dynamics simulations followed by molecular
      mechanics/generalized Born surface area (MM-GBSA) calculations of the ligand
      (epitope peptide) binding energy yielded energy values that were in agreement
      with the ITC measurements and indicated that the charged residues play crucial
      role in the epitope binding. Theoretical arguments presented in this work
      indicate that two adjacent arginine residues (ArgH50 and ArgH52) are responsible
      for the observed proton transfer.

PMID- 18041761
TI  - CO escape from myoglobin with metadynamics simulations.
AB  - The relatively small size of myoglobin makes it suitable for the investigation of
      the ligand escape process in respiratory proteins and, in general, an ideal model
      system for the study of the more general structure-function paradigm. In this
      work, we use Molecular Dynamics simulations combined with an accelerated
      algorithm, the metadynamics, to probe the escape of CO from myoglobin. Our
      approach permits to quantitatively describe the escape process via the
      reconstruction of the associated free energy surface. Additionally, hints on the
      involvement of a larger numbers of residues than hitherto assumed in the gating
      process are extracted from our data.

PMID- 18041762
TI  - Estimating quality of template-based protein models by alignment stability.
AB  - The error in protein tertiary structure prediction is unavoidable, but it is not
      explicitly shown in most of the current prediction algorithms. Estimated error of
      a predicted structure is crucial information for experimental biologists to use
      the prediction model for design and interpretation of experiments. Here, we
      propose a method to estimate errors in predicted structures based on the
      stability of the optimal target-template alignment when compared with a set of
      suboptimal alignments. The stability of the optimal alignment is quantified by an
      index named the SuboPtimal Alignment Diversity (SPAD). We implemented SPAD in a
      profile-based threading algorithm and investigated how well SPAD can indicate
      errors in threading models using a large benchmark dataset of 5232 alignments.
      SPAD shows a very good correlation not only to alignment shift errors but also
      structure-level errors, the root mean square deviation (RMSD) of predicted
      structure models to the native structures (i.e. global errors), and local errors
      at each residue position. We have further compared SPAD with seven other quality
      measures, six from sequence alignment-based measures and one atomic statistical
      potential, discrete optimized protein energy (DOPE), in terms of the correlation
      coefficient to the global and local structure-level errors. In terms of the
      correlation to the RMSD of structure models, when a target and a template are in
      the same SCOP family, the sequence identity showed a best correlation to the
      RMSD; in the superfamily level, SPAD was the best; and in the fold level, DOPE
      was best. However, in a head-to-head comparison, SPAD wins over the other
      measures. Next, SPAD is compared with three other measures of local errors. In
      this comparison, SPAD was best in all of the family, the superfamily and the fold
      levels. Using the discovered correlation, we have also predicted the global and
      local error of our predicted structures of CASP7 targets by the SPAD. Finally, we
      proposed a sausage representation of predicted tertiary structures which
      intuitively indicate the predicted structure and the estimated error range of the
      structure simultaneously.

PMID- 18041763
TI  - Polyubiquitylation of PARP-1 through ubiquitin K48 is modulated by activated DNA,
      NAD+, and dipeptides.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is the most abundant and the best-studied
      isoform of a family of enzymes that catalyze the polymerization of ADP-ribose
      from NAD(+) onto target proteins. PARP-1 is well known to involve in DNA repair,
      genomic stability maintenance, transcription regulation, apoptosis, and necrosis.
      Polyubiquitylation targets proteins towards degradation and regulates cell cycle
      progression, transcription, and apoptosis. Here we report polyubiquitylation of
      PARP-1 in mouse fibroblasts in the presence of proteasome inhibitor and in full
      length recombinant PARP-1 in vitro under standard ubiquitylation assay conditions
      by immunoprecipitation and immunoblotting. Mutation of ubiquitin K48R but not
      ubiquitin K63R abolishes polyubiquitylation of PARP-1, indicating that K48 of
      ubiquitin was used in the formation of polyubiquitin chain and that ubiquitylated
      PARP-1 is likely destined for degradation. Full-length PARP-1 was ubiquitylated
      most likely at the N-terminal 24 kDa domain of PARP-1 as suggested by the
      inhibition of ubiquitylation by activated DNA and the absence of polyubiquitin in
      the C-terminal 89 kDa PARP-1 derived from caspase-catalyzed cleavage. NAD(+)
      inhibited ubiquitylation of PARP-1, while dipeptides ArgAla and LeuAla enhanced
      ubiquitylation of PARP-1. ATP inhibited the synthesis of poly(ADP-ribose) by PARP
      1 and affinity purified polyubiquitylated PARP-1 was active in PAR synthesis. The
      results suggest polyubiquitylation of PARP-1 could regulate poly(ADP
      ribosyl)ation of nuclear proteins by PARP-1 and consequently apoptosis and PARP-1
      regulated cellular processes through ubiquitin-dependent degradation pathways.

PMID- 18041764
TI  - Overexpression of Par-4 enhances thapsigargin-induced apoptosis via down
      regulation of XIAP and inactivation of Akt in human renal cancer cells.
AB  - The prostate-apoptosis-response-gene-4 (Par-4) protein has been shown to function
      as an effector of cell death in response to various apoptotic stimuli that
      trigger mitochondria and membrane receptor-mediated cell death pathways. We found
      that overexpressing Par-4 by stable transfection sensitizes Caki cells to
      induction of apoptosis by TRAIL and drugs that induce endoplasmic reticulum (ER)
      stress [thapsigargin (TG), tunicamycin (TU) and etoposide]. Ectopic expression of
      Par-4 is associated with decreased levels of XIAP protein in TG-treated cells,
      caused in part by XIAP protein instability and caspase activation. Levels of
      phospho-Akt are decreased in Caki/Par-4 cells to a significantly greater extent
      than in Caki/Vector cells by treatment with TG, and this is in turn associated
      with decreased levels of phospho-PDK1, the kinase upstream of Akt. In conclusion,
      we provide evidence that ectopic expression of Par-4 sensitizes Caki cells to TG
      and that XIAP protein instability and inactivation of Akt are important in
      cellular pathways affected by Par-4.

PMID- 18041766
TI  - The cancer nuclear microenvironment: interface between light microscopic cytology
      and molecular phenotype.
AB  - A definitive diagnosis of cancer may be rendered by microscopic assessment of
      only a few cells in an appropriate clinical setting due to the distinctive
      nuclear structure of most cancer cells in comparison to nuclei of normal human
      cells. The molecular architecture of non-neoplastic human nuclei--of the nuclear
      matrix and of matrix-associated proteins and nucleic acids--is being
      characterized in exquisite molecular detail. What is missing is the application
      of the findings and tools of molecular biology to understanding the cytological
      structure of cancer nuclei. This article delves into the basis of nuclear
      structure at different levels of resolution--light microscopic, electron
      microscopic, and molecular.

PMID- 18041765
TI  - Developmental expression and differential cellular localization of obscurin and
      obscurin-associated kinase in cardiac muscle cells.
AB  - Obscurin and obscurin-associated kinase are two products of the obscurin
      transcriptional unit that encodes a recently identified giant muscle-specific
      protein obscurin. In this study, we characterized the developmental expression
      and cellular localization of obscurin and obscurin-associated kinase in cardiac
      muscle cells. We cloned murine obscurin-associated kinase and found that it is
      abundantly expressed in the heart as two isotypes encoded by 2.2 and 4.9 kb
      sequences. The 2.2 kb isotype of the kinase was more prominently expressed than
      the 4.9 kb isotype. Both obscurin and the kinase-like domains were progressively
      upregulated since the early stages of cardiac development. Obscurin-associated
      kinase was expressed at higher levels than obscurin at early stages of
      cardiomyogenesis. Increasing intensity of obscurin expression in the developing
      heart positively correlated with progressive cell differentiation and was higher
      in the ventricles compared to the atria. These data were supported by the results
      of experiments with primary cardiac cell cultures. Obscurin localization changed
      from a weakly immunopositive diffuse pattern in poorly differentiated cells to an
      intensely immunolabeled cross-striated distribution at the level of mid-A-bands
      and Z-disks during the assembly of the myofibrillar contractile apparatus. In
      dividing myocytes, unlike the interphase cells, obscurin translocated from
      disassembling myofibrils into a diffuse granulated pattern segregated separately
      from alpha-actinin-immunopositive aggregates. Obscurin-associated kinase was
      localized mainly to cell nuclei with increasing incorporation into the Z-disks
      during differentiation. Our results suggest that these two novel proteins are
      involved in the progression of cardiac myogenesis during the transition to
      advanced stages of heart development.

PMID- 18041768
TI  - FGF-1-induced matrix metalloproteinase-9 expression in breast cancer cells is
      mediated by increased activities of NF-kappaB and activating protein-1.
AB  - Matrix metalloproteinase-9 (MMP-9) plays a critical role in tumor invasion and
      metastasis. Here, we investigate the effect of fibroblast growth factor-1 (FGF-1)
      on the expression of MMP-9 in ENU1564, an ethyl-N-nitrosourea-induced rat mammary
      adenocarcinoma cell line. We observed that FGF-1 induces a dose-dependent
      increase in MMP-9 mRNA, protein, and activity in ENU1564 cells. To gain insight
      into the molecular mechanism of MMP-9 regulation by FGF-1, we investigated the
      role of components of PI3K-Akt and MEK1/2-ERK signaling pathways in our system
      since NF-kappaB and AP-1 transcription factor binding sites have been
      characterized in the upstream region of the MMP-9 gene. We demonstrated that FGF
      1 increases Akt phosphorylation, triggers nuclear translocation of NF-kappaBp65,
      and enhances degradation of cytoplasmic IkappaBalpha. Pretreatment of cells with
      LY294002, a PI3K inhibitor, significantly inhibited MMP-9 protein expression in
      FGF-1-treated cells. Conversely, our data show that FGF-1 increases ERK
      phosphorylation in ENU1564 cells, increases c-jun and c-fos mRNA expression in a
      time-dependent manner, and triggers nuclear translocation of c-jun. Pretreatment
      of cells with PD98059, a MEK1/2 inhibitor significantly inhibited MMP-9 protein
      expression in FGF-1 treated cells. Finally, we observed increased DNA binding of
      NF-kappaB and AP-1 in FGF-1-treated cells and that mutation of either NF-kappaB
      or AP-1 response elements prevented MMP-9 promoter activation by FGF-1. Taken
      together, these results demonstrated that FGF-1-induced MMP-9 expression in
      ENU1564 cells is associated with increasing DNA binding activities of NF-kappaB
      and AP-1 and involve activation of a dual signaling pathway, PI3K-Akt and MEK1/2
      ERK.

PMID- 18041769
TI  - Bladder voiding by combined high frequency electrical pudendal nerve block and
      sacral root stimulation.
AB  - AIMS: Uncoordinated contraction of the external urethral sphincter is prevalent
      in individuals with spinal cord injury and can prevent bladder voiding. The aim
      of this study was to demonstrate that complete and reversible sinusoidal high
      frequency alternating current (HFAC) conduction block of the pudendal nerves (PN)
      can eliminate external urethral sphincter activation and produce low residual
      bladder voiding. METHODS: In four cats, tripolar nerve cuff electrodes were
      implanted bilaterally on both pudendal nerves and on both extradural S2 roots.
      Bladder and urethral pressures, bladder volumes and flow were recorded. Bilateral
      HFAC was applied to determine voltage and frequency parameters resulting in
      bilateral PN conduction block. Sacral root stimulation provided bladder
      activation. Randomized sets of voiding trials were conducted with and without
      HFAC PN block. Additional voiding trials were conducted following bilateral PN
      neurotomy to eliminate somatic sphincter resistance and provide an estimate of
      voiding with complete block. RESULTS: Effective bilateral PN block and voiding
      was obtained in three of four animals. Application of bilateral PN HFAC
      stimulation improved voiding from 2 +/- 4% to 77 +/- 18% of the initial bladder
      volume and significantly (P < 0.001) reduced maximum bladder pressure during
      voiding. Voiding in trials with PN block was not significantly different from
      voiding following PN neurotomy (82 +/- 19%, P = 0.51). CONCLUSIONS: These results
      demonstrate that bilateral HFAC block of the PN can produce effective voiding.
      Neural prostheses using this approach may provide an alternative method for
      producing micturition for people with spinal cord injury.

PMID- 18041770
TI  - Diabetes mellitus and female lower urinary tract symptoms: a review.
AB  - Diabetes mellitus (DM) has reached epidemic proportions world wide. Many chronic
      complications of DM, including neuropathy, retinopathy and nephropathy, have been
      well studied and although urologic complications have been recognized since 1935,
      little is known about DM as a pathophysiological risk factor for development of
      lower urinary tract symptoms (LUTS) in women. Diabetic nephropathy, a life
      threatening condition, has received considerable attention in the last few years.
      Diabetic cystopathy, on the other hand, has received far less attention despite
      having a significant impact on quality of life, and with significant individual
      health risks. Initial studies suggested that long standing DM causes paralysis of
      the detrusor muscle leading to voiding difficulties and this has been the
      received wisdom regarding diabetic cystopathy for many years. In this review, we
      discuss what is currently known about lower urinary tract function and urinary
      incontinence in diabetic females, with a critical analysis of the available
      evidence and suggest areas for future research.

PMID- 18041772
TI  - Developmental expression of glutamic acid decarboxylase and of gamma-aminobutyric
      acid type B receptors in the ascidian Ciona intestinalis.
AB  - We describe Ciona intestinalis gamma-aminobutyric acid (GABA)-ergic neurons
      during development, studying the expression pattern of Ci-GAD (glutamic acid
      decarboxylase: GABA synthesizing enzyme) by in situ hybridization. Moreover, we
      cloned two GABA(B) receptor subunits (Ci-GABA(B)Rs), and a phylogenetic analysis
      (neighbor-joining method) suggested that they clustered with their vertebrate
      counterparts. We compared Ci-GAD and Ci-GABA(B)Rs expression patterns in C.
      intestinalis embryos and larvae. At the tailbud stage, Ci-GAD expression was
      widely detected in central and peripheral nervous system (CNS/PNS) precursors,
      whereas Ci-GABA(B)Rs expression was evident at the level of the precursors of the
      visceral ganglion. GABA was localized by immunohistochemistry at the same
      developmental stage. In the larva, Ci-GAD transcripts and GABA immunofluorescence
      were also detected throughout the CNS and in some neurons of the PNS, whereas
      transcripts of both GABA(B) receptor subunits were found mainly in the CNS. The
      expression pattern of Ci-GABA(B)Rs appeared restricted to Ci-GAD-positive
      territories in the sensory vesicle, whereas, in the visceral ganglion, Ci
      GABA(B)Rs transcripts were found in ventral motoneurons that did not express Ci
      GAD. Insofar as GABAergic neurons are widely distributed also in the CNS and PNS
      of vertebrates and other invertebrate chordates, it seems likely that GABA
      signaling was extensively present in the protochordate nervous system. Results
      from this work show that GABA is the most widespread inhibitory neurotransmitter
      in C. intestinalis nervous system and that it can signal through GABA(B)
      receptors both pre- and postsynaptically to modulate different sensory inputs and
      subsequent swimming activity.

PMID- 18041773
TI  - Emergence of cellular markers and functional ionotropic glutamate receptors on
      tangentially dispersed cells in the developing mouse retina.
AB  - Tangential cell dispersion in the retina is a spacing mechanism that establishes
      a regular mosaic organization among cell types and contributes to their final
      positioning. The present study has used the X-inactivation transgenic mouse
      expressing the lacZ reporter gene on one X chromosome. Due to X chromosome
      inactivation, 50% of early progenitor cells express beta-galactosidase (beta
      Gal); therefore, all cells derived from a particular beta-Gal-expressing
      progenitor cell can be identified in labeled columns. The radial segregation of
      clonally related beta-Gal-positive and beta-Gal-negative cells can be used to
      determine whether single cells transgress a clonal boundary in the retina. We
      investigated the extent to which particular cell classes tangentially disperse by
      analyzing the placement of labeled cells expressing particular markers at several
      ages and quantifying their tangential displacement. Retinal neurons expressing
      cell markers at postnatal day (P) 1 have a greater degree of tangential
      dispersion compared with amacrine and bipolar cells at P5-6. We also studied
      whether there is a functional correlation with these dispersion patterns by
      investigating the emergence of functional ionotropic glutamate receptors. To
      determine the degree of functional glutamate receptor activation, agmatine (AGB)
      was used in combination with cell-specific labeling. AGB permeates functional
      glutamate receptor channels following activation with alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA), kainate or N-methyl-D-aspartate (NMDA).
      Within these receptor groups, high concentrations of AMPA, kainate, and NMDA are
      associated with a high degree of tangential dispersion in the adult.
      Developmentally, functional kainate and AMPA receptors were detected by P1 and
      were associated with tangentially dispersed cells. Functional NMDA receptors were
      not detected as early as kainate and AMPA receptors. These results indicate that
      cells generated early during development are more likely to disperse tangentially
      compared with those generated later in development. Therefore, functional AMPA
      and kainate receptors may play a critical role in tangentially displacing cell
      types.

PMID- 18041774
TI  - Expression profile of the cadherin family in the developing Drosophila brain.
AB  - The Drosophila genome encodes 17 members of the cadherin family of adhesion
      molecules, which in vertebrates has been implicated in patterning the nervous
      system through cell and axon sorting. With only a few exceptions all cadherins
      show widespread expression in the larval brain. What expression patterns have in
      common is that 1) they are global, in the sense that all lineages of the central
      brain or optic lobe, or both, show expression; and 2) expression is stage
      specific: some cadherins are expressed only in primary neurons (located closest
      to the neuropile), others in early secondary neurons (near the brain surface), or
      primaries plus late secondaries. The Fat-like cadherins, Fat and Dachsous, as
      well as Cad96Ca and Cad74A, are expressed in the epithelial optic lobe anlagen,
      which matches the widespread epithelial expression of these molecules in the
      embryo. DE-cadherin is restricted to immature secondary neurons and glia; by
      contrast, DN-cadherin, Flamingo, Cad87A, Cad99C, and Calsyntenin-1 appear in
      differentiating primary neurons and, at a later stage, some or all secondary
      neurons. Cad87A is strongly enriched apically in epithelia and in neuronal
      dendrites. Fat-like, Cad86C, Cad88C, Cad89D, and Dret are expressed ubiquitously
      in embryonic and larval brains at low or moderate levels. We conclude from this
      analysis that cadherins are likely to play a role in 'generic' neural functions,
      such as neurite fasciculation, branching, and synapse formation.

PMID- 18041775
TI  - The heterozygous LMNA mutation p.R471G causes a variable phenotype with features
      of two types of familial partial lipodystrophy.
AB  - We report on a novel LMNA mutation (p.R471G) in a proband affected by a syndrome
      comprising partial lipodystrophy, insulin-resistant diabetes, acanthosis
      nigricans, liver steatosis, muscle weakness, and contractures. This phenotype has
      features of both types 1 and 2 familial partial lipodystrophy. The sister and
      father of the proband had the same mutation. The sister was more mildly affected
      and the father was apparently unaffected, demonstrating variable expressivity and
      reduced penetrance for this mutation.

PMID- 18041776
TI  - Heterogeneous expression of SNAP-25 in rat and human brain.
AB  - Synaptosomal associated protein of 25 kDa (SNAP-25) is a SNARE component of the
      exocytotic apparatus involved in the release of neurotransmitter. We used
      multiple-labeling immunofluorescence, confocal microscopy, and ultrastructural
      immunocytochemistry to examine the expression of SNAP-25 in excitatory and
      inhibitory terminals from different rat and human brain areas. Glutamatergic and
      GABAergic terminals were identified by staining for the vesicular glutamate
      transporter (vGLUT1), glutamic acid decarboxylase (GAD67), or the vesicular GABA
      transporter (vGAT). In all examined areas GABAergic terminals did not display
      detectable levels of SNAP-25, whereas glutamatergic terminals expressed the
      protein to a variable extent. Codistribution analysis revealed a high
      colocalization between pixels detecting SNAP-25 labeling and pixels detecting
      vGLUT1 immunoreactivity. On the contrary, a low degree of pixel colocalization,
      comparable to that between two unrelated antigens, was detected between SNAP-25
      and vGAT, thus suggesting a random overlap of immunofluorescence signals. Our
      immunofluorescence evidence was supported by ultrastructural data, which clearly
      confirmed that SNAP-25 was undetectable in GABAergic terminals identified by both
      their typical morphology and specific staining for GABA. Interestingly, our
      ultrastructural results confirmed that a subset of glutamatergic synapses do not
      contain detectable levels of SNAP-25. The present study extends our previous
      findings obtained in rodent hippocampus and provides evidence that SNAP-25
      expression is highly variable between different axon terminals both in rat and
      human brain. The heterogeneous distribution of SNAP-25 may have important
      implications not only in relation to the function of the protein as a SNARE but
      also in the control of network excitability.

PMID- 18041777
TI  - Semaphorins 3A, 3C, and 3F in mesencephalic dopaminergic axon pathfinding.
AB  - By analyzing the mechanisms that govern dopaminergic axon pathfinding from the
      midbrain to the striatum in embryonic rat brains, we identified neuroepithelial
      regions that exert chemotropic effects on mesencephalic dopaminergic axons.
      Explants from the pretectum and the striatum showed an attractive effect, whereas
      those from the midhindbrain boundary, the dorsal thalamus, and the ventral
      thalamus had no effect. Expression of semaphorin (Sema) 3C and Sema3F in the
      pretectum and of Sema3A in the striatum suggested a role for these axon guidance
      molecules in dopaminergic axon pathfinding. When expressed in HEK293 cell
      aggregates, Sema3C had an attractive effect and enhanced axon growth, Sema3A
      enhanced axon growth, and Sema3F had a repulsive effect on dopaminergic axons.
      Antineuropilin-1 and antineuropilin-2 antibodies reduced attraction by the
      pretectum, whereas attraction by the striatum was not affected by the presence of
      antineuropilin-1 antibodies. Moreover, neuropilin-1- and neuropilin-2-soluble Fc
      chimeras reduced the attraction by the pretectum. These results suggest that
      semaphorins may help to establish the dopaminergic projection from the midbrain
      to the striatum during embryonic development.

PMID- 18041778
TI  - Identification of major classes of cholinergic neurons in the nematode
      Caenorhabditis elegans.
AB  - The neurotransmitter acetylcholine (ACh) is specifically synthesized by the
      enzyme choline acetyltransferase (ChAT). Subsequently, it is loaded into synaptic
      vesicles by a specific vesicular acetylcholine transporter (VAChT). We have
      generated antibodies that recognize ChAT or VAChT in a model organism, the
      nematode Caenorhabditis elegans, in order to examine the subcellular and cellular
      distributions of these cholinergic proteins. ChAT and VAChT are found in the same
      neurons, including more than one-third of the 302 total neurons present in the
      adult hermaphrodite. VAChT is found in synaptic regions, whereas ChAT appears to
      exist in two forms in neurons, a synapse-enriched form and a more evenly
      distributed possibly cytosolic form. We have used antibodies to identify the
      cholinergic neurons in the body of larval and adult hermaphrodites. All of the
      classes of putative excitatory motor neurons in the ventral nerve cord appear to
      be cholinergic: the DA and DB neurons in the first larval stage and the AS, DA,
      DB, VA, VB, and VC neurons in the adult. In addition, several interneurons with
      somas in the tail and processes in the tail or body are cholinergic; sensory
      neurons are generally not cholinergic. Description of the normal pattern of
      cholinergic proteins and neurons will improve our understanding of the role of
      cholinergic neurons in the behavior and development of this model organism.

PMID- 18041779
TI  - Identifying interacting residues using Boolean Learning and Support Vector
      Machines: case study on mRFP and DsRed proteins.
AB  - In a protein, interactions exist between amino acid residues that influence the
      protein's structural integrity or stability and thus affect its catalytic
      function. The loss of this interaction due to mutations in these amino acids
      usually leads to a non-functional protein. Probing the sequence space of a
      protein through mutations or recombinations, as performed in directed evolution
      to search for an improved variant, frequently results in such inactive sequences.
      In this work, we demonstrate the use of machine learning to identify such
      interacting residues and the use of template engineering strategies to increase
      the fraction of active variants in a library. We show that using the sequences
      from recombination of monomeric red fluorescent protein (mRFP) and Discosoma red
      fluorescent protein (DsRed), we were able to identify a pair of interacting
      residues using an algorithm based on Boolean Learning and Support Vector
      Machines. The interaction between the identified residues was verified through
      point mutations on the mRFP and DsRed genes. We also show that it is possible to
      use such results to alter the parental genes such that the probability of
      disrupting the important interactions is minimized. This will result in a larger
      fraction of active variants in the recombinant library and allow us to access
      more functional space. We demonstrate this effect by comparing the recombinant
      library of wild-type (WT) DsRed, mRFP and an altered sequence of DsRed with mRFP
      WT genes.

PMID- 18041780
TI  - Simultaneous detection of protozoa in the tissues of snakes by double in situ
      hybridization.
AB  - Different methods have been established for the simultaneous detection of
      different pathogens in tissue samples, each with certain advantages and
      disadvantages. Chromogenic in situ hybridization combines specific molecular
      pathogen detection with microscopic evaluation of pathogen quantity, morphology
      and distribution, as well as associated tissue damage. Furthermore, only a
      minimum of usually costly technical equipment is needed. The aim of our study was
      to detect two different protozoa simultaneously in tissue samples using
      exclusively digoxigenin (DIG)-labeled probes and alkaline phosphatase-coupled
      anti-DIG-antibodies and the chromogens Vector Red and NBT/BCIP with standard
      protocols. Gastrointestinal tissue samples from 15 snakes infected with either
      one or two protozoan species were investigated. All expected protozoa stained
      clearly dark purple or bright red, respectively, depending on the chromogen used.
      This technique can be used in pathogenicity studies of various pathogens in any
      kind of tissue.

PMID- 18041781
TI  - Ultrastructure of hybrid chitosan-glycerol phosphate blood clots by environmental
      scanning electron microscopy.
AB  - Chitosan-based polymers have been extensively studied for biomedical
      applications. Recently, liquid solutions of chitosan in a glycerol phosphate
      buffer (chitosan-GP) with physiological pH and osmolality were mixed with
      autologous blood to form hybrid chitosan-GP/blood implants that improved the
      repair of articular cartilage lesions in a large animal model. The mixture of
      chitosan-GP and blood forms a viscous liquid, which solidifies in minutes via
      normal blood coagulation as well as chitosan-mediated mechanisms. Here we have
      examined the ultrastructure of these chitosan-GP/blood clots as well as regular
      blood clots and chitosan-GP gels, the latter produced by heating. Both unfixed
      and fixed samples of chitosan-GP/blood clots, regular blood clots, and chitosan
      GP gels were investigated by environmental scanning electron microscopy (ESEM) in
      conjunction with energy dispersive X-ray spectrometry (EDS), the former
      permitting direct observation of the ultrastructure in hydrated conditions
      simulating the natural state. By examination of unfixed specimens using ESEM we
      found that chitosan formed a network structure in both chitosan-GP gels and
      chitosan-GP/blood clots; however this structure was altered by aldehyde fixation
      to produce artifactual aggregates of chitosan microparticles. We were also able
      to identify chitosan in chitosan-GP/blood clots by washing samples in low
      concentration NaCl solutions followed by local EDS analyses to identify excess
      chloride versus sodium, and thus presence of cationic chitosan in analyzed
      features. Additional results indicated that the majority of glycerol phosphate
      diffuses freely from chitosan-GP gels (by EDS of phosphorus) and that
      hyperosmotic paraformaldehyde-based fixatives (i.e. 4% w/v) significantly disturb
      erythrocyte morphology in fixed whole blood clots.

PMID- 18041782
TI  - Expression and distribution of S100 protein in the nervous system of the adult
      zebrafish (Danio rerio).
AB  - S100 proteins are EF-hand calcium-binding protein highly preserved during
      evolution present in both neuronal and non-neuronal tissues of the higher
      vertebrates. Data about the expression of S100 protein in fishes are scarce, and
      no data are available on zebrafish, a common model used in biology to study
      development but also human diseases. In this study, we have investigated the
      expression of S100 protein in the central nervous system of adult zebrafish using
      PCR, Western blot, and immunohistochemistry. The central nervous system of the
      adult zebrafish express S100 protein mRNA, and contain a protein of approximately
      10 kDa identified as S100 protein. S100 protein immunoreactivity was detected
      widespread distributed in the central nervous system, labeling the cytoplasm of
      both neuronal and non-neuronal cells. In fact, S100 protein immunoreactivity was
      primarily found in glial and ependymal cells, whereas the only neurons displaying
      S100 immunoreactivity were the Purkinje's neurons of the cerebellar cortex and
      those forming the deep cerebellar nuclei. Outside the central nervous system,
      S100 protein immunoreactivity was observed in a subpopulation of sensory and
      sympathetic neurons, and it was absent from the enteric nervous system. The
      functional role of S100 protein in both neurons and non-neuronal cells of the
      zebrafish central nervous system remains to be elucidated, but present results
      might serve as baseline for future experimental studies using this teleost as a
      model.

PMID- 18041783
TI  - Cholinergic innervation of the frontal cortex: differences among humans,
      chimpanzees, and macaque monkeys.
AB  - Cholinergic innervation of the frontal cortex is important in higher cognitive
      functions and may have been altered in humans relative to other species to
      support human-specific intellectual capacities. To evaluate this hypothesis we
      conducted quantitative comparative analyses of choline acetyltransferase
      immunoreactive axons in cortical areas 9, 32, and 4 among humans, chimpanzees,
      and macaque monkeys. Area 9 of the dorsolateral prefrontal cortex is involved in
      inductive reasoning and specific components of working memory processes, while
      area 32 of the medial prefrontal cortex has been implicated in theory of mind.
      Area 4 (primary motor cortex) was also evaluated because it is not directly
      associated with higher cognitive functions. The findings revealed no quantitative
      species differences in the three cortical areas examined, indicating that human
      cognitive specializations are not related to a quantitative increase in cortical
      cholinergic input. However, species-specific morphological specializations were
      observed. Clusters of cholinergic fibers that may be indicative of cortical
      plasticity events were present in chimpanzees and humans, but not in macaques.
      The other significant morphology noted was the common and distinctive oval or
      ovoid perisomatic staining in macaque cortices. This feature was also
      sporadically observed in chimpanzee cortex. Our findings suggest a potential
      alteration of cortical cholinergic afferents within the prefrontal cortex of
      humans and chimpanzees, to the exclusion of macaque monkeys.

PMID- 18041784
TI  - Maturation of auditory brainstem projections and calyces in the congenitally deaf
      (dn/dn) mouse.
AB  - The deaf dn/dn mouse is a valuable model of human congenital deafness. In this
      study we used the lipophylic dye DiA to trace auditory nerve and cochlear nucleus
      projections in the dn/dn mouse. In both normal and deaf mice, the ipsilateral
      projections from the anteroventral cochlear nucleus (AVCN) to the lateral
      superior olive (LSO), and the contralateral projections from the AVCN to the
      medial nucleus of the trapezoid body (MNTB) were intact. With age, there was a
      noted increase in the fenestration of the endbulb and calyx of Held, and this
      morphological maturation was also observed in the deaf mice, although there was a
      significant difference in total endbulb volume at P20 between normal and deaf
      mice. However, total calyceal volume was not significantly different between
      normal and deaf mice. There was electrophysiological evidence of in vivo
      spontaneous ventral cochlear nucleus activity in normal and deaf animals,
      indicating that this activity may be responsible for the appropriate connectivity
      in the deaf mice. Our results indicate that congenital deafness caused by the
      dn/dn mutation does not result in aberrant projections between the AVCN and the
      ipsilateral MNTB and contralateral LSO but can cause abnormalities in endbulb
      size.

PMID- 18041785
TI  - Cholinergic input from the ventral nucleus of the trapezoid body to cochlear root
      neurons in rats.
AB  - Brain stem pathways are essential for the modulation of the acoustic startle
      reflex by sounds; nevertheless, the neural circuits that convey fast auditory
      information to the primary acoustic startle circuit are still unclear. In the
      rat, cochlear root neurons (CRNs) comprise the first component of the primary
      acoustic startle circuit and are critical in the initiation and full expression
      of the acoustic startle reflex. To determine whether CRNs receive auditory
      descending inputs, we developed tract-tracing studies combined with
      immunohistochemistry, electron microscopy, morphometry, and confocal microscopy.
      Either FluoroGold or biotinylated dextran amine (BDA) injections in CRNs showed
      retrogradely labeled neurons in the ventral nucleus of the trapezoid body (VNTB).
      We verified the projection to CRNs by injecting BDA into the VNTB. Our results
      showed that neurons from VNTB project bilaterally and directly to CRNs, giving
      off numerous endings onto cell bodies and preferentially dendrites of CRNs.
      Electron microscopy analysis of labeled VNTB terminals demonstrated that they
      made multiple symmetric synapses and contained small round vesicles.
      Colocalization of the vesicular acetylcholine transporter and fluorescein dextran
      after injection in the VNTB indicated that these terminals use acetylcholine as
      neurotransmitter. We also revealed that the inferior colliculus, an important
      nucleus mediating the auditory prepulse inhibition, projects to VNTB neurons that
      innervate CRNs. Our data show a novel and short descending auditory pathway from
      the VNTB to the first nucleus of the primary acoustic startle circuit that might
      play an important role in the auditory prepulse inhibition of the startle reflex
      elicited by sounds.

PMID- 18041786
TI  - Organization of the olfactory pathway and odor processing in the antennal lobe of
      the ant Camponotus floridanus.
AB  - Ants rely heavily on olfaction for communication and orientation. Here we provide
      the first detailed structure-function analyses within an ant's central olfactory
      system asking whether in the carpenter ant, Camponotus floridanus, the olfactory
      pathway exhibits adaptations to processing many pheromonal and general odors.
      Using fluorescent tracing, confocal microscopy, and 3D-analyses we demonstrate
      that the antennal lobe (AL) contains up to approximately 460 olfactory glomeruli
      organized in seven distinct clusters innervated via seven antennal sensory
      tracts. The AL is divided into two hemispheres regarding innervation of glomeruli
      by either projection neurons (PNs) with axons leaving via the medial (m) or
      lateral (l) antennocerebral tract (ACT). M- and l-ACT PNs differ in their target
      areas in the mushroom-body calyx and lateral horn. Three additional ACTs project
      to the lateral protocerebrum only. We analyzed odor processing in AL glomeruli by
      retrograde loading of PNs with Fura-2 dextran and fluorimetric calcium imaging.
      Odor responses were reproducible and comparable across individuals. Calcium
      responses to pheromonal and nonpheromonal odors were very sensitive (10(-11)
      dilution) and patterns were partly overlapping, indicating that processing of
      both odor classes is not spatially segregated within the AL. Response patterns to
      the main trail-pheromone component nerolic acid remained stable over a wide range
      of intensities (7-8 log units), while response durations increased indicating
      that odor quality is maintained by a stable pattern and intensity is mainly
      encoded in response durations. The structure-function analyses contribute new
      insights into important aspects of odor processing in a highly advanced insect
      olfactory system.

PMID- 18041790
TI  - DNA-mediated assembly of boron nitride nanotubes.
AB  - The dispersion of nanomaterials in solutions is of primary importance for the
      improvement of their processability, but it also provides a way to investigate
      phase behavior and to assemble nanostructures in solvents. Several methods based
      on different interactions have been developed to disperse carbon nanotubes,
      whereas little development has been made for their boron nitride nanotube (BNNT)
      counterparts. A direct way to obtain long-range ordering may be through
      spontaneous nematic ordering in solutions at sufficiently high concentrations of
      the nanomaterial fraction. Lyotropic nematics have been observed in various
      organic and inorganic systems. In this work, the strong interactions between DNA
      and BNNTs were exploited to fabricate high-concentration BNNTs aqueous solutions
      by a simple method, and then, for the first time, nematic ordered ensembles of
      BNNTs were obtained by filtration. It is proposed that a localized liquid-crystal
      phase appears during filtration, as the ordering trend for the BNNTs was found to
      depend on the concentration of the aqueous solutions of the BNNTs. Moreover,
      BNNTs were successfully localized on a predefined area by using a thiol-modified
      DNA-BNNT hybrid.

PMID- 18041793
TI  - Simultaneous detection of five different 2-hydroxyethyl-DNA adducts formed by
      ethylene oxide exposure, using a high-performance liquid
      chromatography/electrospray ionisation tandem mass spectrometry assay.
AB  - A method has been developed for the simultaneous detection and quantitation of
      five different 2-hydroxyethyl-DNA (HE-DNA) adducts that could be formed as a
      result of exposure to ethylene oxide (EO). In addition to the major N7-HE-guanine
      (N7-HEG) adducts this assay can also measure the less prevalent but potentially
      more biologically significant N1-HE-2'-deoxyadenosine (N1-HEdA), O(6)-HE-2'
      deoxyguanosine (O(6)-HEdG), N(6)-HE-2'-deoxyadenosine (N(6)-HEdA) and N3-HE-2'
      deoxyuridine adducts (N3-HEdU). The method involves the isolation of HE adducts
      from the unmodified nucleosides by either neutral thermal hydrolysis or enzymatic
      digestion, followed by high-performance liquid chromatographic (HPLC)
      purification, before detection and quantification by liquid chromatography tandem
      mass spectrometry (LC/MS/MS) using selective reaction monitoring (SRM). The
      limits of detection were in the range 0.5-25 fmol for each individual adduct,
      making this one of the most sensitive assays available for the detection of N7
      HEG. To illustrate the possible applications of the assay, it has been employed
      in the measurement of endogenous/background and EO-induced HE adducts in a
      variety of DNA samples.

PMID- 18041794
TI  - Prevalence of clinically significant depressive symptoms in an epidemiologic
      sample of community-dwelling elders with milder forms of cognitive impairment in
      Hong Kong SAR.
AB  - BACKGROUND: Depression and cognitive impairment in later-life have great bearings
      on public health. The two conditions often co-occur and have mutual implications
      on short-term risk and long-term prognosis. METHOD: A two-phase epidemiologic
      survey on the prevalence of dementia in elders aged 60 and over was conducted in
      Hong Kong in 2005-2006. In the first phase, 6,100 randomly selected community
      dwelling elders were assessed with Cantonese version of Mini-Mental State
      Examination (C-MMSE) and Abbreviated Memory Inventory for Chinese (AMIC). Two
      thousand and seventy-three subjects were screened positive and invited for second
      phase cognitive and psychiatric assessment. 35.5% of screen-positive subjects
      participated in Phase 2 assessment conducted by psychiatrists for diagnosis of
      dementia. Severity of dementia was determined using Clinical Dementia Rating
      Scale (CDR). Cornell Scale for Depression in Dementia (CSDD) and a structured
      bedside cognitive battery were also administered to each subject. RESULTS: 1.7%
      of subjects with CDR 0.5 and 5.9% of subjects with CDR 1 had clinically
      significant depressive symptoms (>or= 8 on CSDD). Score on CSDD correlated
      positively with duration of cognitive symptoms, scores on CIRS and CMMSE in
      linear regression model. In a logistic regression model, male gender, duration of
      cognitive symptoms, CIRS and CMMSE was associated with increased risk for
      clinically significant depressive symptoms. CONCLUSIONS: In our sample, milder
      forms of cognitive impairment were associated with increased risk for depression
      in the presence of other risk factors such as male gender, higher physical
      illness burden and longer duration of cognitive symptoms.

PMID- 18041795
TI  - Mass spectrometry analysis of in vitro nitration of a recombinant human IgG1
      monoclonal antibody.
AB  - Nitration of a recombinant human monoclonal antibody was carried out in vitro by
      incubating the antibody with the nitrating reagent tetranitromethane (TNM). The
      susceptible sites of nitration were identified using high-performance liquid
      chromatography/mass spectrometry (HPLC/MS). In general, tyrosine residues in the
      variable domains of the antibody are more susceptible to nitration, while
      tyrosine residues in the constant domains are relatively resistant to nitration.
      However, one tyrosine residue in the CH1 domain and one tyrosine residue in the
      CH2 domain are highly susceptible to nitration. Interestingly, the susceptible
      tyrosine residue in the CH2 domain is followed by the conserved asparagine
      residue that is glycosylated.

PMID- 18041796
TI  - Ultrasensitive fluorescent responses of water-soluble, zwitterionic, boronic acid
      bearing, regioregular head-to-tail polythiophene to biological species.
AB  - Water-soluble regioregular head-to-tail zwitterionic fluorescent conjugated
      boronic acid-bearing polythiophene (polymer 2) was prepared through a
      postpolymerization quaternization of a pyridine group of 3-pyridineboronic acid
      with bromide groups of regioregular head-to-tail poly(3-bromohexylthiophene)
      (polymer 1). Titration of monosaccharides, lactose, ascorbic acid, or dopamine
      with 0.1 M phosphate buffer (pH 7.4), containing 4.0 microM of polymer 2, results
      in significant concentration-dependent quenching of the polymer fluorescence. The
      polymer displays an optimum response to the biological species at pH 7.0. The
      binding constants of polymer 2 with mannose, fructose, glucose, galactose,
      vitamin C, dopamine, and lactose are 3.33 x 10(4), 1.13 x 10(5), 1.23 x 10(5),
      1.69 x 10(5), 3.17 x 10(5), 3.27 x 10(5), and 4.60 x 10(5), respectively.

PMID- 18041797
TI  - Quantitative conformational study of redox-active [2]rotaxanes, part 2: Switching
      in flexible and rigid bistable [2]rotaxanes.
AB  - Translational movement of the macrocycle in two structurally similar bistable
      [2]rotaxanes, which is induced by a four-step electrochemical process in
      solution, has been investigated by using a methodology developed in the preceding
      article (Chem. Eur. J. 2008, 14, 1107-1116). Both [2]rotaxanes contain a crown
      ether that can be accommodated by either of two interconnected viologen
      recognition sites. These sites are substantially different in terms of their
      affinity towards the crown ether and they possess considerably different
      electrochemical reduction potentials. The two [2]rotaxanes differ in the length
      and the rigidity of a bridge that links these sites. A combination of molecular
      mechanics modelling and NOE spectroscopy data provides information about the
      conformations of both [2]rotaxanes in the parent oxidation state when the crown
      ether exclusively populates the strong recognition site. To determine the
      population of the recognition sites at subsequent stages of reduction, a
      paramagnetic NMR technique and cyclic voltammetry were used. The key finding is
      that the flexibility of the connecting bridge element between the recognition
      sites interferes with shuttling of the crown ether in [2]rotaxanes. It can be
      demonstrated that the more flexible trimethylene bridge is folded, thus limiting
      the propensity of the crown ether to shuttle. Consequently, the crown ether
      populates the original site even in the second reduced state of the flexible
      [2]rotaxane. On the contrary, in the [2]rotaxane in which two viologen sites are
      connected by a larger and more rigid p-terphenylene bridge, the predominant
      location of the crown ether at the weak recognition site is achieved after just
      one single electron reduction.

PMID- 18041798
TI  - Polymer-fullerene composite solar cells.
AB  - Fossil fuel alternatives, such as solar energy, are moving to the forefront in a
      variety of research fields. Polymer-based organic photovoltaic systems hold the
      promise for a cost-effective, lightweight solar energy conversion platform, which
      could benefit from simple solution processing of the active layer. The function
      of such excitonic solar cells is based on photoinduced electron transfer from a
      donor to an acceptor. Fullerenes have become the ubiquitous acceptors because of
      their high electron affinity and ability to transport charge effectively. The
      most effective solar cells have been made from bicontinuous polymer-fullerene
      composites, or so-called bulk heterojunctions. The best solar cells currently
      achieve an efficiency of about 5%, thus significant advances in the fundamental
      understanding of the complex interplay between the active layer morphology and
      electronic properties are required if this technology is to find viable
      application.

PMID- 18041799
TI  - Aluminum triflate as a highly active and efficient nonprotic cocatalyst in the
      palladium-catalyzed methoxycarbonylation reaction.

PMID- 18041800
TI  - Catalytic enantioselective 1,6-conjugate addition of Grignard reagents to linear
      dienoates.

PMID- 18041801
TI  - The total synthesis of chlorotonil A.

PMID- 18041802
TI  - Single-molecule magnets with mesomorphic lamellar ordering.

PMID- 18041803
TI  - Shining new light on an old problem: retooling MALDI mass spectrometry for
      organotransition-metal catalysis.

PMID- 18041804
TI  - Compartmental relaxation and diffusion tensor imaging measurements in vivo in
      lambda-carrageenan-induced edema in rat skeletal muscle.
AB  - Integrated diffusion tensor T(2) measurements were made on normal and edematous
      rat muscle, and the data were fitted with one- and two-compartment models,
      respectively. Edematous muscle exhibited a short-lived component (T(2) = 28 +/- 6
      ms), with diffusion characteristics similar to that of normal muscle, and a long
      lived component (T(2) = 96 +/- 27 ms), with greater mean apparent diffusion
      coefficient (ADC) and lower fractional anisotropy (FA). With this two-component
      description of diffusion and relaxation, values of ADC and FA estimated with a
      conventional pulsed-gradient spin-echo sequence will depend on the echo time,
      relative fraction of short-lived and long-lived water signals, and the intrinsic
      ADC and FA values within the tissue. On the basis of the relative differences in
      water diffusion properties between long-lived and short-lived water signals, as
      well as the similarities between the short-lived component and normal tissue, it
      is postulated that these two signal components largely reflect intracellular and
      extracellular water.

PMID- 18041805
TI  - Relationships between MR transverse relaxation parameters R*(2), R(2) and R'(2)
      and hepatic iron content in thalassemic mice at 1.5 T and 3 T.
AB  - Assessment of hepatic iron concentration is important in the management of
      patients with thalassemia. The goal of this study was to investigate the
      relationships between the three MR transverse relaxation rates, R*(2), R(2) and
      R'(2), and hepatic iron content in a mouse model of thalassemia at 1.5 and 3 T
      field strengths. A GESFIDE (gradient-echo sampling of free induction decay and
      echo) pulse sequence was used to measure the three parameters efficiently in a
      single scan in a study examining the livers of normal and thalassemic mice,
      including a subgroup of the latter that were subjected to periodic transfusions.
      The results showed that R*(2), R(2) and R'(2) all correlated closely with liver
      iron concentration at both 1.5 T and 3 T, with correlation coefficients ranging
      from 0.72 to 0.79. High degrees of correlation (r = 0.93-0.99) were also observed
      among the three MR parameters at both field strengths. It can be concluded that
      the three rates could all be effective for assessing hepatic iron concentration
      and that imaging at higher fields may not offer any advantages over that at lower
      fields.

PMID- 18041806
TI  - Axonal injury detected by in vivo diffusion tensor imaging correlates with
      neurological disability in a mouse model of multiple sclerosis.
AB  - Recent studies have suggested that axonal damage, and not demyelination, is the
      primary cause of long-term neurological impairment in multiple sclerosis and its
      animal model, experimental autoimmune encephalomyelitis (EAE). The axial and
      radial diffusivities derived from diffusion tensor imaging have shown promise as
      non-invasive surrogate markers of axonal damage and demyelination, respectively.
      In this study, in vivo diffusion tensor imaging of the spinal cords from mice
      with chronic EAE was performed to determine if axial diffusivity correlated with
      neurological disability in EAE assessed by the commonly used clinical scoring
      system. Axial diffusivity in the ventrolateral white matter showed a significant
      negative correlation with EAE clinical score and was significantly lower in mice
      with severe EAE than in mice with moderate EAE. Furthermore, the greater
      decreases in axial diffusivity were associated with greater amounts of axonal
      damage, as confirmed by quantitative staining for non-phosphorylated
      neurofilaments (SMI32). Radial diffusivity and relative anisotropy could not
      distinguish between the groups of mice with moderate EAE and those with severe
      EAE. The results further the notion that axial diffusivity is a non-invasive
      marker of axonal damage in white matter and could provide the necessary link
      between pathology and neurological disability.

PMID- 18041808
TI  - The prevention and treatment (and cost) of cancer.

PMID- 18041807
TI  - Lung cancer and regular use of aspirin and nonaspirin nonsteroidal anti
      inflammatory drugs.
AB  - PURPOSE: Lung cancer is the leading cause of cancer death in the US. There is
      evidence of a reduced risk of some cancer sites associated with use of aspirin
      (ASA) and nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs). Our
      objective was to examine the association of regular use of ASA and NANSAIDs with
      lung cancer. METHODS: A hospital-based case-control study of 1884 incident cases
      of lung cancer and 6251 controls with noncancer diagnoses. Use of ASA and
      NANSAIDs was considered 'regular' if it occurred on > or =4 days/week and lasted
      for > or =3 months. Logistic regression was used to estimate odds ratios (OR) and
      95% confidence intervals. RESULTS: The OR for regular use of ASA was 1.1 (0.9
      1.4), and the corresponding estimate for regular NANSAID use was 1.0 (0.7-1.3).
      There was no evidence of decreased risk within strata of age, sex, years of
      education, or interview year. Examining the association within strata of duration
      of use, recency of use, cigarette smoking status, pack-years of cigarette
      smoking, or histologic type of cancer produced no ORs significantly different
      from 1.0. CONCLUSIONS: The hypothesis that regular use of ASA or NANSAIDs reduces
      the risk of lung cancer is not supported by the present data.

PMID- 18041812
TI  - Yin-yang ways of controlling gene expression are now in our hands.
AB  - Molecular biologists have long dreamed of switching genes on and off at will in
      any part of the body during embryonic development. Their dream is now coming true
      thanks to the transparency of the embryonic body of the zebrafish ( Danio rerio),
      which has made gene manipulation by photoillumination possible.

PMID- 18041813
TI  - First glimpse of the crystal structure of YaeT's POTRA domains.
AB  - The Omp85/YaeT family of proteins, which are conserved from bacteria to human,
      catalyzes insertion and assembly of proteins in the outer membrane. The structure
      consists of a transmembrane beta-barrel domain and a soluble polypeptide
      transport-associated (POTRA) domain. The POTRA domain is critical for substrate
      recognition and perhaps substrate folding, while the beta-barrel domain assists
      in membrane insertion. The resolution of the crystal structure of the POTRA
      domain of the Escherichia coli YaeT protein provides a possible molecular
      mechanism by which the diverse group of substrates is recognized. Knowledge
      gained from the crystal structure may also spur the development of a novel class
      of chemotherapeutic inhibitors.

PMID- 18041814
TI  - Signaling by committee: receptor clusters determine pathways of cellular
      activation.
AB  - Receptor clustering is a common signaling mechanism for cell surface receptors.
      Exogenous ligands such as antibodies or synthetic analogues can be used to
      artificially induce clustering. New studies using defined synthetic ligands
      suggest that the spatial organization of these clusters attenuates signaling in
      one pathway but has no effect in another.

PMID- 18041815
TI  - Metal sensing by RNA in bacteria: exception or rule?
AB  - Until 2006, it was believed that bacteria control their intracellular metal ion
      concentrations exclusively through metal-sensing proteins. However, the detection
      of the first riboswitch that uses a small ion, Mg2+, as ligand to regulate gene
      expression in Salmonella challenged this assumption. Now, the discovery and in
      depth characterization of a second metal-ion-sensing riboswitch that seems to be
      ubiquitously present in Gram-positive bacteria suggest that metal sensing by RNAs
      may represent a widespread mechanism.

PMID- 18041816
TI  - Chemical proteomics identifies unanticipated targets of clinical kinase
      inhibitors.
AB  - Kinases represent one of the most important target classes of current drug
      discovery efforts. However, because the vast majority of potential small-molecule
      therapeutics is directed toward the highly conserved ATP-binding cleft, kinase
      inhibitors often exhibit significant unintended off-target effects. A recent
      report describes a chemical proteomics methodology that enables the simultaneous
      in vivo quantification of the on- and off-binding targets of kinase inhibitors
      across hundreds of nucleotide-dependent enzymes.

PMID- 18041818
TI  - Exploring the structural diversity of mammalian carbohydrates ("glycospace") by
      statistical databank analysis.
AB  - The diversity of three major classes of mammalian carbohydrates, mainly
      glycolipids and O- and N-linked glycans, deposited in the databank
      GLYCOSCIENCES.de was subjected to statistical analyses. Size, chain length, and
      branching complexity were accessed and revealed that the average oligosaccharide
      is composed of about eight monosaccharide units. About a quarter of all
      oligosaccharides are strictly linear, and the remainder are branched at least
      once. Glucosamine, galactose, and mannose are dominating and comprise ~75% of the
      monosaccharides within mammalian oligosaccharide frameworks. alpha-Linked sialic
      acid, alpha-linked fucose, and beta-linked galactose decorate the majority of
      reducing termini. Glucose as the most abundant carbohydrate in mammals plays only
      a very minor role within these structures. Particular emphasis was placed on
      analyzing the way the monosaccharide units are linked within the oligomeric
      framework. Just 11 monosaccharide connections account for >75% of all linkages.
      Thus, the number of structural combinations found in nature, the part of the
      occupied mammalian glycospace, is much smaller than expected. As a result, a
      potential set of building blocks for oligosaccharide assembly is presented. This
      potential building block set was correlated with the accessible 3299 mammalian
      carbohydrate structures in the GLYCOSCIENCES.de databank. Only 36 building blocks
      are required to construct 75% of the 3299 mammalian oligosaccharides.

PMID- 18041817
TI  - Trivalent ligands with rigid DNA spacers reveal structural requirements for IgE
      receptor signaling in RBL mast cells.
AB  - Antigen-mediated cross-linking of IgE bound to its receptor, FcRI, stimulates
      degranulation, phospholipid metabolism, and cytokine production in mast cells and
      basophils to initiate inflammatory and allergic responses. Previous studies
      suggested that spatial organization of the clustered receptors affects the
      assembly of the transmembrane signaling complexes. To investigate systematically
      the structural constraints in signal initiation, we utilized rigid double
      stranded DNA scaffolds to synthesize ligands with tunable lengths. We
      characterized a series of symmetric trivalent DNA ligands with rigid spacing
      between 2,4-dinitrophenyl (DNP) haptenic groups in the range of 5-15 nm. These
      ligands all bind to anti-DNP IgE on RBL mast cells with similar avidity, and they
      all cross-link IgE-FcRI complexes effectively. We observe length-dependent
      stimulation of tyrosine phosphorylation of FcRI beta and gamma subunits and the
      adaptor protein LAT: the shortest ligand is approximately 5-10-fold more potent
      than the longest. Stimulated Ca2+ mobilization and degranulation also exhibits
      kinetics and magnitudes that differ as a function of ligand length. In contrast,
      tyrosine phosphorylation of phospholipase Cgamma1 and consequent Ca2+ release
      from intracellular stores do not show this dependence on ligand length. Our
      results with these rigid, DNA-based ligands provide direct support for receptor
      transphosphorylation as a key step in amplified signaling leading to
      degranulation, and they further reveal branching of pathways in signaling events.

PMID- 18041819
TI  - Temperature-triggered self-assembly of ZnO: from nanocrystals to nanorods to
      tablets.
AB  - ZnO nanocrystals, nanorods, and tablets were prepared at 110, 140, and 180
      degrees C in a water-ethanol system. Nanorods (~2 x 40 nm) arranged in serpentine
      morphologies formed by the oriented coalescence of anhedral ZnO nanocrystals
      (~3.5 nm diameter), while tabular ZnO grew by [1210] textural attachment of the
      nanorods. The development of these crystal habits is believed to proceed via a
      dissolution and growth mechanism mediated by a transient amorphous phase.
      Materials synthesized at intermediate temperatures (125 and 160 degrees C)
      possessed microstructures containing mixed crystal forms in the expected
      orientation relationship. Photoluminescent spectra of the nanocrystals and
      nanorods showed blue shifts of 0.16 and 0.13 eV with respect to the bulk ZnO band
      gap (3.26 eV) due to quantum confinement, with the narrow emission peaks typical
      of particles possessing uniform size and shape. The larger tablets displayed a
      less energetic emission (3.10 eV) ascribed to exciton-exciton collisions.

PMID- 18041820
TI  - Lateral diffusion of thiol ligands on the surface of au nanoparticles: an
      electron paramagnetic resonance study.
AB  - The lateral mobility of the thiolate ligands on the surface of Au nanoparticles
      was probed by EPR spectroscopy. This was achieved by using bisnitroxide ligands,
      which contained a disulfide group (to ensure attachment to the Au surface) and a
      cleavable ester bridge connecting the two spin-labeled branches of the molecule.
      Upon adsorption of these ligands on the surface of Au nanoparticles, the two spin
      labeled branches were held next to each other by the ester bridge as evidenced by
      the spin-spin interactions. Cleavage of the bridge removed the link that kept the
      branches together. CW and pulsed EPR (DEER) experiments showed that the average
      distance between the adjacent thiolate branches on the Au nanoparticle surface
      only marginally increased after cleaving the bridge and thermal treatment. This
      implies that the lateral diffusion of thiolate ligands on the nanoparticle
      surface is very slow at room temperature and takes hours even at elevated
      temperatures (90 degrees C). The changes in the distance distribution observed at
      high temperature are likely due to ligands hopping between the nanoparticles
      rather than diffusing on the particle surface.

PMID- 18041821
TI  - Electrochemical determination of HIV drug Abacavir based on its reduction.
AB  - Abacavir (I), a drug used in the treatment of HIV, is electrochemically reduced
      at the dropping mercury electrode in a four-electron process, similar to
      structurally related adenine (III) and adenosine triphosphate (IV). To undergo
      the reduction, the species is protonated in the vicinity of the electrode. The
      protonations take place on the 6-amino group and on one of the pyrimidine ring
      nitrogens. The role of covalent hydration of the pyrymidine ring has been
      interpreted. Best suited as supporting electrolytes for analytical purposes are
      solutions of 0.1-1.0 M sulfuric, perchloric, or hydrochloric acids. Procedures of
      analyses of tablets containing I were established and validated, based on peak
      currents obtained by linear sweep, differential pulse, or square-wave voltammetry
      with a hanging mercury drop electrode as indicator electrode. The procedure
      proved to be more sensitive and more reliable than that based on oxidation on a
      glassy carbon electrode, proposed previously.

PMID- 18041822
TI  - Practically modified attenuated total reflection surface-enhanced IR absorption
      spectroscopy for high-quality frequency-extended detection of surface species at
      electrodes.
AB  - A practically modified ATR configuration has been proposed for in situ
      electrochemical surface-enhanced IR absorption spectroscopy (SEIRAS) by
      sandwiching an ultrathin water interlayer between a hemicylindrical ZnSe prism
      and a Si wafer as an integrated window. This new ATR optics significantly
      enhances the throughput of an effective IR beam across the ZnSe/gap/Si/metal
      film, enabling high-quality spectral fingerprints down to 700 cm(-1) to be
      readily detected at larger incidence angles without compromising the
      electrochemical feasibility and stability of metallic films deposited on Si. The
      advantages of this modified ATR-SEIRAS have been initially applied to explore two
      selected systems: wide-ranged in situ ATR-SEIRA spectra provided strong evidence
      in support of the formate intermediate pathway for methanol electrooxidation at
      the Pt electrode in an acid solution; in addition, new spectral fingerprints
      revealed comprehensive orientational information about of the p-nitrobenzoate
      species at Pt electrode as a result of the dissociative adsorption of p
      nitrobenzoic acid molecules from an acid solution.

PMID- 18041823
TI  - Luminescence studies of perturbation of tryptophan residues of tubulin in the
      complexes of tubulin with colchicine and colchicine analogues.
AB  - Tubulin, a heterodimeric (alphabeta) protein, the main constituent of
      microtubules, binds efficiently with colchicine (consisting of a
      trimethoxybenzene ring, a seven-member ring and methoxy tropone moiety) and its
      analogues, viz., demecolcine and AC [2-methoxy-5-(2',3',4'
      trimethoxyphenyl)tropone]. Tubulin contains eight tryptophan (Trp) residues at
      A21, A346, A388, A407, B21, B103, B346, and B407 in the two subunits. The role of
      these eight Trp residues in this interaction and also their perturbation due to
      binding have been explored via time-resolved fluorescence at room temperature and
      low-temperature (77 K) phosphorescence in a suitable cryosolvent. Both the time
      resolved fluorescence data and 77 K phosphorescence spectra indicate that the
      emitting residues move toward a more hydrophobic and less polar environment after
      complex formation. The environment of emitting Trps in the complex also becomes
      slightly more heterogeneous. Our analysis using the experimental results, the
      calculation of the accessible surface area (ASA) of all the Trps in the wild type
      and tubulin-colchicine complex [Ravelli, R. B. G., et al. (2004) Nature 428, 198
      202], the distance of the Trp residues from the different moieties of the
      colchicine molecule, the knowledge of the nature of the immediate residues (<5 A)
      present near each Trp residue, and the calculation of the intramolecular Trp-Trp
      energy transfer efficiencies indicate that Trp A346, Trp A407, Trp B21, and Trp
      B407 are the major contributors to the emission in the free protein, while Trp
      B21 and Trp B103 are mainly responsible for the emission of the complexes. A
      comparative account of the photophysical aspects of the drug molecules bound to
      protein in aqueous buffer and in buffer containing 40% ethylene glycol has been
      presented. The quantum yield and average lifetime of fluorescence in tubulin and
      its complexes with colchicine are used to predict the possible donors and the
      energy transfer (ET) efficiency in the ET process from Trps to colchicine in the
      complex. This study is a unique attempt to identify the Trp residues contributing
      to the emission in the free protein and in a complex of a multi-Trp protein with
      a drug molecule without performing the mutation of the protein.

PMID- 18041824
TI  - Theoretical study of the benzyl+O2 reaction: kinetics, mechanism, and product
      branching ratios.
AB  - Ab initio calculations at the level of CBS-QB3 theory have been performed to
      investigate the potential energy surface for the reaction of benzyl radical with
      molecular oxygen. The reaction is shown to proceed with an exothermic barrierless
      addition of O2 to the benzyl radical to form benzylperoxy radical (2). The
      benzylperoxy radical was found to have three dissociation channels, giving
      benzaldehyde (4) and OH radical through the four-centered transition states
      (channel B), giving benzyl hydroperoxide (5) through the six-centered transition
      states (channel C), and giving O2-adduct (8) through the four-centered transition
      states (channel D), in addition to the backward reaction forming benzyl radical
      and O2 (channel E). The master equation analysis suggested that the rate constant
      for the backward reaction (E) of C6H5CH2OO-->C6H5CH2+O2 was several orders of
      magnitude higher that those for the product dissociation channels (B-D) for
      temperatures 300-1500 K and pressures 0.1-10 atm; therefore, it was also
      suggested that the dissociation of benzylperoxy radicals proceeded with the
      partial equilibrium between the benzyl+O2 and benzylperoxy radicals. The rate
      constants for product channels B-D were also calculated, and it was found that
      the rate constant for each dissociation reaction pathway was higher in the order
      of channel D>channel C>channel B for all temperature and pressure ranges. The
      rate constants for the reaction of benzyl+O2 were computed from the equilibrium
      constant and from the predicted rate constant for the backward reaction (E).
      Finally, the product branching ratios forming CH2O molecules and OH radicals
      formed by the reaction of benzyl+O2 were also calculated using the stationary
      state approximation for each reaction intermediate.

PMID- 18041825
TI  - Local density enhancement in supercritical carbon dioxide studied by Raman
      spectroscopy.
AB  - The polarized IVV and depolarized IVH Raman profiles of the Fermi dyad (1285 cm(
      1) and 1388 cm(-1)) of supercritical (SC) CO2 have been measured along the
      isotherms 307, 309, 313, and 323 K in the reduced density range
      0.04<rho*=rho/rhoC<2.04 (rhoC is the critical density). A band shape analysis of
      the dyad component shows that each one can be decomposed in two well-defined
      Lorentzian profiles in all of the temperature and density ranges investigated.
      These profiles have been assigned with the transitions of CO2 probing two kinds
      of environments. In each dyad peak, the Lorentzian profiles centered at higher
      frequency is associated with CO2 interacting through usual Van der Waals
      interactions with its nearest neighbors. The Lorentzian profiles centered at
      lower frequency in each dyad peak have been related to the transition of CO2
      involved in a transient (CO2)2 dimer. The evolution with the density of the band
      center positions and bandwidths of the Lorentzian profiles shaping the lower and
      upper dyad components exhibits a nonlinear behavior along the near critical
      isotherm (307 K) for rho* ranging from 0.4 to 1.7. This behavior, although less
      pronounced, is still detected at higher temperatures. The deviation from
      linearity was interpreted as being due to an enhancement of the density that
      leads to a reduced local density excess Deltarho*=rho*loc-rho*bulk. Even if the
      spectroscopic observables involved probe the interactions in SC CO2 differently,
      we emphasize that the scaled spectral features are straightforwardly related to
      the Local Density Enhancement (LDE) phenomenon taking place in SC fluids (SCF).
      We show that the LDE effect can also be put in evidence from the band shape
      analysis of the weak satellite band situated at 1370 cm(-1) associated with the
      upper Fermi dyad transition of the 13C16O2 molecule (1% isotopic natural
      abundance). The asymmetric shape of the evolution with density of the Deltarho*
      found from our spectroscopic observables shows some similitude with that obtained
      in a recent MD simulation [Skarmoutsos, I.; Samios, J. J. Chem. Phys. 2007, 126,
      44503.] and the possible inter-connection and difference with these calculations
      are discussed.

PMID- 18041826
TI  - A quantitative scale for the extent of conjugation of the amide bond. Amidity
      percentage as a chemical driving force.
AB  - The amide bond may be considered as one of the most important chemical building
      blocks, playing an important role not only in living organisms but in organic
      chemistry as well. The exact description and precise quantification of the amide
      bond strength is difficult, requiring a particular type of theoretical
      investigation. The present paper suggests a novel, yet simple, method toward
      quantifying amide bond strength on a linear scale, defined as the "amidity
      scale". This is achieved using the computed enthalpy of hydrogenation (DeltaHH2)
      of the compound examined. In the present conceptual work, the DeltaHH2 value for
      dimethylacetamide is used to define perfect amidic character (amidity=+100%),
      while azaadamantane-2-on represents complete absence of amidic character
      (amidity=0%). The component DeltaHH2 values were computed at differing levels of
      theory, providing a computational and quasi-"method-independent" measure of
      amidity. A total of 29 well-known amides were examined to demonstrate the
      "scoring" accuracy of this methodology. For the compounds examined, a correlation
      has been made between the computed amidity percentage and their common COSNAR
      resonance energy values, proton affinities, and reactivity in a nucleophilic
      addition reaction. Selected chemical reactions were also studied. It has been
      shown that the change of the amidity value, during acyl transfer reactions,
      represents a thermodynamic driving force for the reaction.

PMID- 18041827
TI  - Computational study of iron(II) systems containing ligands with nitrogen
      heterocyclic groups.
AB  - Density functional theory (DFT) calculations show the higher energy HOMO (highest
      occupied molecular orbital) orbitals of four iron(II) diimine complexes are metal
      centered and the lower energy LUMO (lowest unoccupied molecular orbitals) are
      ligand centered. The energy of the orbitals correlates with electrochemical redox
      potentials of the complexes. Time-dependent density functional theory (TDDFT)
      calculations reveal ligand centered (LC) and metal-to-ligand charge transfer
      (MLCT) at higher energy than experimentally observed. TDDFT calculations also
      reveal the presence of d-d transitions which are buried under the MLCT and LC
      transitions. The difference in chemical and photophysical behavior of the iron
      complexes compared to that of their ruthenium analogues is also addressed.

PMID- 18041828
TI  - Classification of dynamic vibronic couplings in vibrational real-time spectra of
      a thiophene derivative by few-cycle pulses.
AB  - Pump-probe spectroscopy was performed with a few cycle pulses of 6.7 fs duration.
      The electronic transition intensity modulation was induced by molecular vibration
      in a quinoid thiophene molecule in solution. The real-time vibrational features
      were analyzed in terms of dependence of vibrational amplitude and phase on probe
      photon energy. The electronic transition probability is modulated by molecular
      vibration via vibronic coupling. Changes in the spectral shape and intensity of
      the time-resolved spectrum were studied by tracking characteristic spectral
      features including the peak frequency and intensity, spectral bandwidth, and band
      integrated intensity. From the analysis the modulation mechanisms were classified
      into two groups: (1) Condon type and (2) non-Condon type. The features of the
      wave packet motions were also classified into zeroth-order derivatives due to
      quasi-pure non-Condon type and first- and second-order derivative types due to
      the displacement of the potential minimum and the potential curvature change
      associated with the relevant vibronic transition, respectively.

PMID- 18041829
TI  - Facilitated hydride binding in an Fe-Fe hydrogenase active-site biomimic revealed
      by X-ray absorption spectroscopy and DFT calculations.
AB  - Iron-only hydrogenases are high-efficiency biocatalysts for the synthesis and
      cleavage of molecular hydrogen. Their active site is a diiron center, which
      carries CO and CN ligands. Remarkably, the two iron atoms likely are connected by
      a non-protein azadithiolate (adt = S-CH2-NH-CH2-S). To dwell on the role of the
      adt in H2 catalysis, a specific biomimetic diiron compound, 1 = [Fe2(mu-adt-CH2
      Ph)(CO)4(PMe3)2], with unprecedented positive reduction potential, has been
      synthesized and crystallized previously. It comprises two protonation sites, the
      N-benzyl-adt nitrogen that can hold a proton (H) and the Fe-Fe bond that will
      formally carry a hydride (Hy). We investigated changes in the solution structure
      of 1 in its four different protonation states (1', [1H]+, [1HHy]2+, and [1Hy]+)
      by X-ray absorption spectroscopy at the iron K-edge. EXAFS reveals that already
      protonation at the adt nitrogen atom causes a change of the ligand geometry
      involving a significant lengthening of the Fe-Fe distance and CO and PMe3
      repositioning, respectively, thereby facilitating the subsequent binding of a
      bridging hydride. Hydride binding clearly is discernible in the XANES spectra of
      [1HHy]2+ and [1Hy]+. DFT calculations are in excellent agreement with the
      experimentally derived structural parameters and provide complementary insights
      into the electronic structure of the four protonation states. In the iron-only
      hydrogenases, protonation of the putative adt ligand may cause the bridging CO to
      move to a terminal position, thereby preparing the active site for hydride
      binding en route to H2 formation.

PMID- 18041830
TI  - Structural versatility of 5-methyltetrazolato complexes of (eta5
      pentamethylcyclopentadienyl)iridium(III) incorporating 2,2'-bipyridine, N,N
      dimethyldithiocarbamate, or 2-pyridinethiolate ligands.
AB  - Several new mono- and dinuclear eta (5)-pentamethylcyclopentadienyl (Cp*)
      iridium(III) complexes bearing 5-methyltetrazolate (MeCN 4 (-)) have been
      synthesized and their molecular and crystal structures have been determined. For
      complexes incorporating 2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen), both
      mononuclear kappa N (2)-coordinated and dinuclear mu-kappa N (1):kappa N (3)
      bridging MeCN 4 complexes were obtained: [Cp*Ir(bpy or phen)(MeCN 4-kappa N
      (2))]PF 6 ( 1 or 3) and [{Cp*Ir(bpy or phen)} 2(mu-MeCN 4-kappa N (1):kappa N
      (3))](PF 6) 3 ( 2 or 4), respectively. It was confirmed by X-ray analysis that
      the dinuclear complex in 2 has a characteristic structure with a pyramidal pocket
      constructed from a mu-kappa N (1):kappa N (3)-bridging MeCN 4 (-) and two bpy
      ligands. In the case of analogous complexes with N, N-dimethyldithiocarbamate (Me
      2dtc (-)), yellow platelet crystals of mononuclear kappa N (1)-coordinated
      complex, [Cp*Ir(Me 2dtc)(MeCN 4-kappa N (1))].HN 4CMe ( 5.HN 4CMe), and yellow
      prismatic crystals of dinuclear mu-kappa N (1):kappa N (4)-bridging one,
      [{Cp*Ir(Me 2dtc)} 2(mu-MeCN 4-kappa N (1):kappa N (4))]PF 6 ( 6), were deposited.
      The kappa N (1)- and kappa N (1):kappa N (4)-bonding modes of MeCN 4 (-) in these
      complexes presumably arise from the compactness of the Me 2dtc (-) coligand. 6 is
      the first example in which tetrazolates act as a mu-kappa N (1):kappa N (4)
      bridging ligand. Furthermore, the molecular and crystal structures of dinuclear
      complexes having mu-kappa (2) S, N:kappa S-bridging 2-pyridinethiolate (2-Spy (
      )) or 8-quinolinethiolate (8-Sqn (-)) ligands have been determined: [(Cp*Ir) 2(mu
      2-Spy or 8-Sqn-kappa (2) S, N:kappa S) 2] ( 7 or 8). These thiolato-bridging
      complexes were stable toward the addition of 5-methyltetrazole (HN 4CMe), owing
      to the characteristic intramolecular stacking interaction between the pyridine or
      the quinoline rings. The 2-Spy complex of 7, however, reacted with an excess
      amount of Na(N 4CMe), resulting in cleavage of the IrN(py) bond and coordination
      of MeCN 4 (-) in the mu-kappa N (2):kappa N (3)-bridging mode: [(Cp*Ir) 2(mu-2
      Spy-kappa S:kappa S) 2(mu-MeCN 4-kappa N (2):kappa N (3))]PF 6 ( 9). This
      bridging mode of MeCN 4 (-) was also observed in the triply bridging MeCN 4
      complex: [(Cp*Ir) 2(mu-MeCN 4-kappa N (2):kappa N (3)) 3]PF 6 ( 10). In these
      various MeCN 4 complexes, the structural parameters of the MeCN 4 moiety were not
      perturbed by the difference in the bonding modes.

PMID- 18041831
TI  - Mechanism of the Morita-Baylis-Hillman reaction: a computational investigation.
AB  - Accurate calculations are presented on the mechanism of the MBH reaction,
      focusing on the reaction between methyl acrylate and benzaldehyde, catalyzed by a
      tertiary amine. We address the mechanism under protic solvent-free conditions,
      but also consider how the mechanism and rate-limiting step change in the presence
      of alcohols. We have carefully calibrated the DFT method used in the calculations
      by carrying out high-level G3MP2 calculations on a model system. All of our
      calculations also treat the effect of solvent, described as a dielectric
      continuum. In the absence of protic solvent, we predict that deprotonation of the
      alpha-position is the rate-determining step and occurs through a cyclic
      transition state, with proton transfer to a hemiacetal alkoxide formed by
      addition of a second equivalent of aldehyde to the intermediate alkoxide. As
      first suggested by McQuade, this mechanism explains the observed second-order
      kinetics with respect to aldehyde concentration in the absence of protic solvent.
      In contrast, in the presence of methanol, we find a slightly lower energy
      pathway, in which the alcohol serves as a shuttle to transfer the proton from
      carbon to oxygen. Overall, the barrier to reaction for the latter mechanism is of
      24.6 kcal/mol with respect to reactants at the B3LYP level of theory. The
      relative energy for the addition transition state of the amine-acrylate betaine
      adduct to the aldehyde is much lower, at 16.0 kcal/mol relative to reactants, so
      C-C bond formation should not be rate-limiting, except perhaps for some aliphatic
      aldehydes or imines. We discuss the implications of this mechanism for the design
      of asymmetric versions of the MBH reaction, given the overwhelming importance of
      the proton-transfer step.

PMID- 18041832
TI  - Steric effects in electron transfer from potassium to pi-bonded oriented
      molecules CH3CN, CH3NC, and CCl3CN.
AB  - Electron transfer from K atoms to oriented CH3CN, CH3NC, and CCl3CN is studied in
      crossed beams at energies near the threshold for forming an ion pair. For the
      methyl compounds, the dominant ions are K+ and CN-; the steric asymmetry is very
      small and energy-independent, characteristic of sideways attack with the electron
      apparently entering the pi*CN antibonding orbital. Migration of the electron to
      the sigma*CC orbital to break the C-C bond is greatly facilitated by interaction
      with the atomic donor. CH2CN- is formed in collisions preferring CH3-end attack,
      and the steric asymmetry becomes very large near threshold. CCl3CN mostly forms
      Cl- in collisions slightly favoring the CCl3 end with a small energy dependence
      with the electron apparently entering the sigma* LUMO. CN- is formed in much
      smaller yield with a slight preference for the CN end. The parent negative ion
      CCl3CN- is observed, and a lower limit for its electron affinity is estimated to
      be 0.3 eV. Fragment ions CCl2CN- and CClCN- are also observed with upper limits
      for the quantity bond dissociation energy - electron affinity (BDE - EA)
      estimated to be 0.6 and 1.0 eV, respectively.

PMID- 18041833
TI  - Structure-guided design of AMP mimics that inhibit fructose-1,6-bisphosphatase
      with high affinity and specificity.
AB  - AMP binding sites are commonly used by nature for allosteric regulation of
      enzymes controlling the production and metabolism of carbohydrates and lipids.
      Since many of these enzymes represent potential drug targets for metabolic
      diseases, efforts were initiated to discover AMP mimics that bind to AMP-binding
      sites with high affinity and high enzyme specificity. Herein we report the
      structure-guided design of potent fructose 1,6-bisphosphatase (FBPase) inhibitors
      that interact with the AMP binding site on FBPase despite their structural
      dissimilarity to AMP. Molecular modeling, free-energy perturbation calculations,
      X-ray crystallography, and enzyme kinetic data guided our redesign of AMP, which
      began by replacing the 5'-phosphate with a phosphonic acid attached to C8 of the
      adenine base via a 3-atom spacer. Additional binding affinity was gained by
      replacing the ribose with an alkyl group that formed van der Waals interactions
      with a hydrophobic region within the AMP binding site and by replacing the purine
      nitrogens N1 and N3 with carbons to minimize desolvation energy expenditures. The
      resulting benzimidazole phosphonic acid, 16, inhibited human FBPase (IC50 = 90
      nM) 11-fold more potently than AMP and exhibited high specificity for the AMP
      binding site on FBPase. 16 also inhibited FBPase in primary rat hepatocytes and
      correspondingly resulted in concentration-dependent inhibition of the
      gluconeogenesis pathway. Accordingly, these results suggest that the AMP site of
      FBPase may represent a potential drug target for reducing the excessive glucose
      produced by the gluconeogenesis pathway in patients with type 2 diabetes.

PMID- 18041834
TI  - Discovery of potent and specific fructose-1,6-bisphosphatase inhibitors and a
      series of orally-bioavailable phosphoramidase-sensitive prodrugs for the
      treatment of type 2 diabetes.
AB  - Excessive glucose production by the liver coupled with decreased glucose uptake
      and metabolism by muscle, fat, and liver results in chronically elevated blood
      glucose levels in patients with type 2 diabetes. Efforts to treat diabetes by
      reducing glucose production have largely focused on the gluconeogenesis pathway
      and rate-limiting enzymes within this pathway such as fructose-1,6-bisphosphatase
      (FBPase). The first potent FBPase inhibitors were identified using a structure
      guided drug design strategy (Erion, M. D.; et al. J. Am. Chem. Soc. 2007, 129,
      15480-15490) but proved difficult to deliver orally. Herein, we report the
      synthesis and characterization of a series of orally bioavailable FBPase
      inhibitors identified following the combined discoveries of a low molecular
      weight inhibitor series with increased potency and a phosphonate prodrug class
      suitable for their oral delivery. The lead inhibitor, 10A, was designed with the
      aid of X-ray crystallography and molecular modeling to bind to the allosteric AMP
      binding site of FBPase. High potency (IC50 = 16 nM) and FBPase specificity were
      achieved by linking a 2-aminothiazole with a phosphonic acid. Free-energy
      perturbation calculations provided insight into the factors that contributed to
      the high binding affinity. 10A and standard phosphonate prodrugs of 10A exhibited
      poor oral bioavailability (0.2-11%). Improved oral bioavailability (22-47%) was
      achieved using phosphonate diamides that convert to the corresponding phosphonic
      acid by sequential action of an esterase and a phosphoramidase. Oral
      administration of the lead prodrug, MB06322 (30, CS-917), to Zucker Diabetic
      Fatty rats led to dose-dependent inhibition of gluconeogenesis and endogenous
      glucose production and consequently to significant blood glucose reduction.

PMID- 18041835
TI  - Direct probing molecular twist and tilt in aromatic self-assembled monolayers.

PMID- 18041836
TI  - Antimicrobial activity and protease stability of peptides containing fluorinated
      amino acids.
AB  - Selective fluorination of peptides results in increased chemical and thermal
      stability with simultaneously enhanced hydrophobicity. We demonstrate here that
      fluorinated derivatives of two host defense antimicrobial peptides, buforin and
      magainin, display moderately better protease stability while retaining, or
      exhibiting significantly increased bacteriostatic activity. Four fluorinated
      analogues in the buforin and two in the magainin series were prepared and
      analyzed for (1) their ability to resist hydrolytic cleavage by trypsin; (2)
      their antimicrobial activity against both gram-positive and gram-negative
      bacterial strains; and (3) their hemolytic activity. All but one fluorinated
      peptide (M2F5) showed retention, or significant enhancement, of antimicrobial
      activity. The peptides also showed modest increases in protease resistance,
      relative to the parent peptides. Only one of the six fluorinated peptides
      (BII1F2) was degraded by trypsin at a slightly faster rate than the parent
      peptide. Hemolytic activity of peptides in the buforin series was essentially
      null, while fluorinated magainin analogues displayed an increase in hemolysis
      compared to the parent peptides. These results suggest that fluorination may be
      an effective strategy to increase the stability of biologically active peptides
      where proteolytic degradation limits therapeutic value.

PMID- 18041837
TI  - Electrostatically "patchy" coatings via cooperative adsorption of charged
      nanoparticles.
AB  - Solutions containing oppositely charged nanoparticles (NPs) deposit "patchy"
      coatings of alternating charge distribution on various types of materials,
      including polymers, elastomers, and semiconductors. Surface adsorption of the NPs
      is driven by cooperative electrostatic interactions and does not require chemical
      ligation or layer-by-layer schemes. The composition and the quality of the
      coatings can be regulated by the types, the charges, and the relative
      concentrations of the NPs used and by the pH. Dense coatings form on flat,
      curvilinear, or micropatterned surfaces, are stable against common chemicals for
      prolonged periods of time, and can be used in applications ranging from bacterial
      protection to plasmonics.

PMID- 18041838
TI  - A computational investigation of allostery in the catabolite activator protein.
AB  - The catabolite activator protein is a dimer that consists of two cAMP-binding
      subunits, each containing a C-terminus DNA-binding module and a N-terminus ligand
      binding domain. The system is well-known to exhibit negative cooperativity,
      whereby the binding of one cAMP molecule reduces the binding affinity of the
      other cAMP molecule by 2 orders of magnitude, despite the large separation
      between the cAMP binding pockets. Here we use extensive explicit-solvent
      molecular dynamics simulations (135 ns) to investigate the allosteric mechanism
      of CAP. Six trajectories were carried out for apo, singly liganded, and doubly
      liganded CAP, both in the presence and absence of DNA. Thorough analyses of the
      dynamics through the construction of dynamical cross-correlated maps, as well as
      essential dynamics analyses, indicated that the system experienced a switch in
      motion as a result of cAMP binding, in accordance with recent NMR experiments
      carried out on a truncated form of the protein. Analyses of conformer structures
      collected from the simulations revealed a remarkable event: the DNA-binding
      module was found to dissociate from the N-terminus ligand binding domain. An
      interesting aspect of this structural change is that it only occurred in
      unoccupied subunits, suggesting that the binding of cAMP provides additional
      stability to the system, consistent with the increase in entropy that was
      observed in our calculations and from isothermal titration calorimetry. Analysis
      of the distribution of intrinsic disorder propensities in CAP amino acid sequence
      using PONDR VLXT and VSL1 predictors revealed that the region connecting ligand
      binding and DNA-binding domains of CAP have the potential to exhibit increased
      flexibility. We complemented these trajectories with free energy calculations
      following the MM-PBSA approach on more than 2000 snapshots that included 880
      normal mode analysis. The resulting free energy differences between the singly
      liganded and doubly liganded states were in excellent agreement with isothermal
      titration calorimetry data. When the free energy calculations were carried out in
      the presence of DNA, we discovered that a switch in cooperativity occurred, so
      that the binding of the first cAMP promoted the binding of the other cAMP. The
      components of the free energy reveal that this effect is mainly entropic in
      nature, whereby the DNA reduces the degree of tightening that is observed in its
      absence, thereby promoting binding of the second cAMP. This finding prompted us
      to propose a new mechanism by which CAP triggers the transcription activation
      that is based on an order to disorder transition mediated by cAMP binding as well
      as DNA.

PMID- 18041839
TI  - A new labeling method for methyl transverse relaxation-optimized spectroscopy NMR
      spectra of alanine residues.

PMID- 18041840
TI  - Magnetic field effect studies indicate reduced geminate recombination of the
      radical pair in substrate-bound adenosylcobalamin-dependent ethanolamine ammonia
      lyase.
AB  - The apparent conflict between literature evidence for (i) radical pair (RP)
      stabilization in adenosylcobalamin (AdoCbl)-dependent enzymes and (ii) the
      manifestation of magnetic field sensitivity due to appreciable geminate
      recombination of the RP has been reconciled by pre-steady-state magnetic field
      effect (MFE) investigations with ethanolamine ammonia lyase (EAL). We have shown
      previous stopped-flow MFE studies to be insensitive to magnetically induced
      changes in the net forward rate of C-Co homolytic bond cleavage. Subsequently, we
      observed a magnetic-dependence in the continuous-wave C-Co photolysis of free
      AdoCbl in 75% glycerol but have not done so in the thermal homolysis of this bond
      in the enzyme-bound cofactor in the presence of substrate. Consequently, in the
      enzyme-bound state, the RP generated upon homolysis appears to be stabilized
      against the extent of geminate recombination required to observe an MFE. These
      findings have strong implications for the mechanism of RP stabilization and the
      unprecedented catalytic power of this important class of cobalamin-dependent
      enzymes.

PMID- 18041841
TI  - Synthesis of single-crystalline niobate nanorods via ion-exchange based on molten
      salt reaction.

PMID- 18041842
TI  - Microcontact printing using the spontaneous reduction of aryldiazonium salts.

PMID- 18041844
TI  - Experimental investigation into the mechanism of the epoxidation of aldehydes
      with sulfur ylides.
AB  - A mechanistic study of the epoxidation of aldehydes with sulfur ylides has been
      carried out. The DeltaG++ of the reaction was determined to be 22.2 kcal/mol at
      298 K. A 13C kinetic isotope effect was determined to be 1.026 for the carbonyl
      carbon of benzaldehyde. A secondary deuterium isotope effect was determined to be
      0.93 for the aldehydic hydrogen atom of benzaldehyde. Substituent effects on
      reaction rate were studied, and a Hammett rho of +2.50 was found.

PMID- 18041845
TI  - Lewis Acid promoted tandem intermolecular Diels-Alder/intramolecular allylation
      reactions of silyl-substituted 1,3-butadienes leading to multisubstituted 7
      norbornenones and related polycyclic compounds.
AB  - 7-Norbornenones of exo,exo-disubstituted patterns were formed highly selectively
      in good yields from Lewis acid-promoted tandem intermolecular Diels
      Alder/intramolecular allylation reactions. The intermolecular Diels-Alder
      reaction between 1,4-bis(trimethylsilyl)-1,3-butadienes or 1-trimethylsilyl-1,3
      butadienes with maleic anhydride in the presence of newly sublimed AlCl3 afforded
      their corresponding cycloaddition adducts, which underwent AlCl3-mediated
      intramolecular allylation of the carbonyl group by the in situ generated
      allylsilane moiety affording 7-norbornenones of exo,exo-disubstituted patterns.

PMID- 18041846
TI  - Synthesis of photoactive analogues of a cystine knot trypsin inhibitor protein.
AB  - We describe the preparation of a recently described photoactive amino acid
      analogue (photoMethionine) by two novel synthetic routes, one of which is
      flexible and enantiospecific, and the site-specific chemical incorporation of
      photoMethionine into a defined and functionally active protein using a
      combination of solid-phase peptide synthesis and modern chemical ligation
      methodology. Site-specific labeling of proteins with this amino acid analogue
      through chemical synthesis provides valuable probes for photoaffinity cross
      linking studies.

PMID- 18041847
TI  - Virtually complete E-selective alpha,beta-unsaturated ester synthesis by Hg(OTf)2
      catalyzed hydration of sec-ethoxyalkynyl acetate.
AB  - The reaction of alkyl-substituted sec-ethoxyalkynyl acetates with water catalyzed
      by Hg(OTf)2 afforded alpha,beta-unsaturated esters in excellent yield with high
      catalytic turnover up to 1000 times under very mild reaction conditions with
      virtually complete E-selectivity, superior even to that of the HWE reaction.

PMID- 18041848
TI  - Amino Acid derived enamides: synthesis and aminopeptidase activity.
AB  - Recently developed copper-catalyzed coupling methodology has been applied to the
      synthesis of amino acid derived enamides. Bond formation proved to be strongly
      influenced by protection strategy and vinyl iodide substitution while tolerant of
      limited side chain functionality. Assessment of aminopeptidase activity revealed
      a preference for (E)-1,2-disubstituted constructs.

PMID- 18041851
TI  - Rupture work of pendular bridges.
AB  - Capillary bridging can generate substantial forces between solid surfaces.
      Impacted technologies and sciences include micro- and nanomachining, disk drive
      interfaces, scanning probe microscopy, biology, and granular mechanics. Existing
      calculations of the rupture work of capillary bridges do not consider the
      thermodynamics relating to the evaporation that can occur in the case of volatile
      liquids. Here, we show that the occurrence of evaporation decreases the rupture
      work by a factor of about 2. The decrease arises from heat taken from the
      surroundings that is converted into work. The treatment is based on a
      thermodynamic control-volume analysis of the pendular bridge geometry. We extend
      the mathematical formulation of Orr et al., solving the meniscus problem exactly
      for non-wetting surfaces. The extension provides analytical results for
      conditions at the rupture point and at a possible inflection point and for the
      rupture work. A simple equation (eq 32) is shown to fit the rupture work for the
      two cases over a meniscus curvature range of 3 orders of magnitude. Coefficients
      for the equation are given in tabular form for different contact angle pairs.

PMID- 18041850
TI  - Copper-catalyzed [4 + 1] cycloadditions of alpha,beta-acetylenic ketones with
      diazoacetates to form trisubstituted furans.
AB  - Copper-catalyzed [4 + 1] cycloaddition reaction of alpha,beta-acetylenic ketones
      with alpha-diazo esters offers an efficient, direct route to highly substituted
      furans. The reaction conditions and the scope of the process are examined, and a
      possible mechanism is proposed.

PMID- 18041852
TI  - Nanoscale assemblies of gigantic molecular {Mo154}-rings:
      (dimethyldioctadecylammonium)20[Mo154O462H8(H2O)70].
AB  - Clusters based on the mixed-valence gigantic inorganic ring
      [Mo154O462H14(H2O)70]14- ({Mo154}-ring) and dimethyldioctadecylammonium (DODA)
      were combined to form novel molecular assemblies of an inorganic-organic hybrid
      molecular system as Langmuir-Blodgett (LB) and cast films.
      (DODA)20[Mo154O462H8(H2O)70] (2) was prepared by cation exchange and was
      characterized by a combination of thermogravimetry, IR, UV-vis-NIR, 1H NMR, and
      XRD measurements. The salt 2 was soluble in common organic solvents, and the
      chemical stability of {Mo154}-ring encapsulated by DODA cationic surfactants in
      CHCl3 was found to be higher than that of the "native" sodium salt of the {Mo154}
      ring in H2O. Uniform spherical vesicle-like molecular assemblies of
      (DODA)20[Mo154O462H8(H2O)70] were observed in dilute THF, whose average diameter
      of 95 nm and a normalized variance of 5.7% were confirmed by a X-ray small-angle
      scattering. Deposition of 2 as a cast film showed circular domains with a typical
      diameter of approximately 100 nm, indicating possible similarities between
      solution and surface-deposited structures. The resulting LB films of salt 2 were
      transferred from an acidic buffer subphase with pH = 1.5 onto mica, giving a two
      dimensional film surface with a unity transfer ratio. Further, the electronic
      absorption spectra of the LB multilayer were consistent with the classic type II
      mixed-valence MoV/MoVI electronic state well know for molybdenum blue {Mo154}
      ring systems, and it appears that on the surface the plane of the {Mo154}-ring is
      approximately parallel to the substrate surface, as indicated by polarized
      electronic spectra, while the alkyl chains of DODA were relatively normal to the
      substrate surface. Therefore, the layer between the {Mo154}-rings and DODA
      cations was alternately stacked along the direction of film propagation. Finally,
      it was found that the surface morphology of the cast and LB films was determined
      by the molecular assembly of (DODA)20[Mo154O462H8(H2O)70] in solution and the air
      water interface, respectively.

PMID- 18041853
TI  - Diatom structures templated by phase-separated fluids.
AB  - An experimentally motivated model is proposed for the formation of fluid-phase
      templates corresponding to the porous silica skeletons of diatoms, single-cell
      organisms found in marine and freshwater environments. It is shown that phase
      separation processes on a planar surface may give rise to a quasi-static mold
      that could direct the deposition of condensing silica to form complex arrays of
      pores. Calculations show that appropriate fluid templates can be generated for a
      wide variety of diatom species. The results could be of some biological
      relevance, but the most significant advance may be the identification of a
      synthetic strategy for generating complex porous architectures from simple,
      amorphous materials.

PMID- 18041854
TI  - Hydrophobic and Hofmeister effects on the adhesion of spider silk proteins onto
      solid substrates: an AFM-based single-molecule study.
AB  - AFM-based single-molecule force spectroscopy has been used to study the effect of
      Hofmeister salts and protein hydrophobicity on the adhesion of recombinant spider
      silk proteins onto solid substrates. Therefore, a molecular probe consisting of a
      spider silk protein and an AFM tip has been developed, which (i) is a well
      defined, small system that can be simulated by molecular dynamics simulations,
      (ii) allows access to the whole soluble concentration range for ions, and (iii)
      provides the distribution of desorption forces rather than just ensemble-averaged
      mean values. The measured desorption forces follow the Hofmeister series for
      anions (H2PO4-, Cl-, I-) with a stabilizing energy of more than 15 kBT for 5 M
      NaH2PO4. Moreover, this effect is influenced by the hydrophobicity of the spider
      silk protein, indicating that hydrophobic and Hofmeister effects are closely
      related.

PMID- 18041855
TI  - Electrochemical quartz crystal microbalance study of azurin adsorption onto an
      alkanethiol self-assembled monolayer on gold.
AB  - A quartz crystal microbalance coupled with electrochemistry was used to examine
      the adsorption of azurin on a gold electrode modified with a self-assembled
      monolayer of octanethiol. Azurin adsorbed irreversibly to form a densely packed
      monolayer. The rate of azurin adsorption was related to the bulk concentration of
      azurin in solution within the concentration range studied. At a high azurin
      concentration (2.75 muM), adsorption was rapid with a stable adsorption maximum
      attained in 2-3 min. At a lower azurin solution concentration (0.35 muM), the
      time to reach a stable adsorption maximum was approximately 30 min.
      Interestingly, the maximum surface concentration attained for all solution
      concentrations studied by the QCM method was 25 +/- 1 pmol cm-2, close to that
      predicted for monolayer coverage. The dissipation was monitored during
      adsorption, and only small changes were detected, implying a rigid adsorption
      model, as needed when using the Sauerbrey equation. Cyclic voltammetric data were
      consistent with a one-electron, surface-confined CuII/CuI azurin process with
      fast electron-transfer kinetics. The electroactive surface concentration
      calculated using voltammetry was 7 +/- 1 pmol cm-2. The differences between the
      QCM and voltammetrically determined surface coverage values reflect,
      predominantly, the different measurement methods but imply that all surface
      confined azurin is not electrochemically active on the time scale of cyclic
      voltammetry.

PMID- 18041857
TI  - Two-dimensional molecular space with regular molecular structure.
AB  - A novel two-dimensional molecular space (layered carboxylpropylamidephenylsilica,
      CPAPhS) with regular carboxyl groups was successfully synthesized through
      grafting carboxyl groups in the structure of layered (aminophenyl)silica using
      butanedioic anhydride. The carboxyl groups regularly arranged in the layered
      CPAPhS can react with various organic molecules with amino and hydroxyl groups
      through formation of reactive intermediate with catalyzers, such as SOCl2. In
      this research, an example was used to prove the reaction properties of regular
      carboxyl groups in layered CPAPhS. The layered CPAPhS was reacted with SOCl2 to
      form layered acyl chloridepropylamidephenylsilica (ACPAPhS) and then reacted with
      n-butylamine and n-butyl alcohol to form layered n
      butylamidepropylamidephenylsilica (BAPAPhS) and n
      butylesterpropylamidephenylsilica (BEPAPhS) with regular molecular structures.
      Layered CPAPhS showed the potential as a starting material for formation of a
      series of novel two-dimensional molecular space with various regular molecular
      structures, and as a solid acceptor for chemical reagent with amino and hydroxyl
      groups for chemical processes.

PMID- 18041856
TI  - Optically active supramolecular complex formed by ionic self-assembly of cationic
      perylenediimide derivative and adenosine triphosphate.
AB  - Ionically self-assembled complex between a water-soluble perylenediimide (PDI)
      derivative, N,N'-bis(propylenetrimethylammonium)-3,4,9,10-perylenediimide (BPTA
      PDI), and adenosine triphosphate (ATP) has been prepared. Absorption, emission,
      and circular dichroism (CD) spectroscopic techniques were used to monitor the
      complex formation. It was found that, upon the addition of ATP into the solution
      of an intrinsically achiral BPTA-PDI, the complex exhibits a unique split-type
      induced CD (ICD) in the pi-pi* transition region of the PDI chromophore,
      indicating that the molecular chirality of nucleotides is expressed in the
      perylene moiety through the multiple electrostatic interactions. The influences
      of BPTA-PDI concentration, temperature, and adenosine nucleotides bearing
      different numbers of phosphate groups on the chirality induction to BPTA-PDI were
      also investigated. On the basis of extensive investigations performed with
      absorption, emission, and CD spectroscopy, a possible mechanism for the formation
      of chiral superstructures is proposed.

PMID- 18041858
TI  - Nanodisk codes.
AB  - We report a new encoding system based upon dispersible arrays of nanodisks
      prepared by on-wire lithography and functionalized with Raman active
      chromophores. These nanodisk arrays are encoded both physically (in a "barcode"
      pattern) and spectroscopically (Raman) along the array. These structures can be
      used in covert encoding strategies because of their small size or as biological
      labels with readout by scanning confocal Raman spectroscopy. As proof-of-concept,
      we demonstrate their utility in DNA detection in a multiplexed format at target
      concentrations as low as 100 fM.

PMID- 18041859
TI  - Identification of DNA basepairing via tunnel-current decay.
AB  - We propose a new approach for reading the sequence of a DNA molecule passing
      between electrodes on a nanopore, using hydrogen bond-mediated tunneling signals.
      The base-electrode interaction is modeled using a nucleo-base-functionalized STM
      probe that is pulled away from a nucleoside monolayer. Watson-Crick recognition
      results in slow decay of the tunnel current, which is uniquely characteristic of
      the basepair in over half the reads. Thirteen independent reads would yield the
      desired 99.99% accuracy.

PMID- 18041865
TI  - Retrospective bibliometric review of rural health research: Australia's
      contribution and other trends.
AB  - INTRODUCTION: The health of half of the world's 6 billion people and of the 6
      million Australians living in rural and remote communities is demonstrably poorer
      than that of their metropolitan counterparts. As the existence of the discrete
      specialty of rural health (RH) is gaining acceptability worldwide, publications
      about RH issues are increasing in prevalence. We undertook a bibliometric
      analysis of Australian rural research trends and compared these with
      international RH research output, and analyzed how Australian RH research has
      been addressing the National Health Priority Areas (NHPAs) during this period.
      METHODS: Medline-listed publications from 1990 to 2005 relating to rural health
      or rural health services were downloaded using PubMed and written to a Microsoft
      Access database using specially developed software. Analysis was performed to
      determine the country of origin of the authors, frequency of journals,
      publication types and how publications addressed Australian NHPAs. RESULTS: We
      retrieved 20 913 rural health publications of which 1442 (6.8%) were from
      Australia. Analysis from 1990 and 2005 showed total world yearly publications
      increased from 410 to 1207, while the respective contribution from Australia
      increased from 17 (4.1%) to 198 (16.4%). Canadian and USA contributions increased
      respectively from 10 (2.4%) to 110 (9.1%) and 131 (32%) to 298 (24.7%). The top
      five journals that published RH articles were Journal of Rural Health (JRH; 453),
      Australian Journal of Rural Health (AJRH; 417), Medical Journal of Australia
      (MJA; 192), Social Science Medicine (191) and Lancet (171). The Australian
      journals with the largest number of RH publications were AJRH (374), MJA (177),
      Australian Family Physician (101), Rural Remote Health (55) and Journal of
      Telemedicine Telecare (54). The most frequent publication type was the journal
      article in all three countries. Australian publications comprised journal
      articles (85.1%), letters (9.1%), reviews (5.6%), editorials (4.7%) and clinical
      trials (2.9%). Australia had the lowest proportion of clinical trials of the
      three countries. Of the total 1290 Australian publications, 317 (25%) addressed
      the NHPAs. Of these, 118 (37.2%) addressed mental health, 54 (17%) cancer, 41
      (12.9%) cardiovascular disease, 37(11.7%) injury prevention, 35(11%) diabetes and
      15 (4.7%) arthritis and musculoskeletal conditions. DISCUSSION: Australia's
      contribution to the international RH literature is increasing, both in terms of
      the relative numerical contribution and the prominence of selected Australian
      journals as the destination for articles on RH topics. Of dedicated RH journals,
      AJRH is now almost as frequently used by authors as JRH. However the general
      journals Lancet, BMJ and MJA were also among the most frequent publishers of RH
      articles. Telemedicine and general practice journals (Australian Family Physician
      & Canadian Family Physician) were also among the top journals that published RH
      articles, which highlights the increasingly prominent role played by information
      and communication technologies in the delivery of rural health care in general
      practice settings. The most frequent NHPA addressed by the RH publications in
      Australia was mental health. However only approximately 1% of total Australian
      health publications from 1990 to 2005 addressed RH. There is still a pressing
      need for more RH research, particularly in health priority areas.

PMID- 18041866
TI  - Collaborative care and motivational interviewing: improving depression outcomes
      through patient empowerment interventions.
AB  - Patient empowerment interventions have demonstrated significant success in the
      treatment of several chronic conditions. Recently, 2 such interventions,
      collaborative care and motivational interviewing, have been employed in the
      treatment of depression with promise in the managed care setting. Collaborative
      care initiatives feature a multidisciplinary team of providers to deliver such
      services as patient education, thorough follow-up, and case management.
      Motivational interviewing employs specifically tailored dialogue to encourage
      patients to take an active role in their therapy. Through increased treatment
      adherence and improved outcomes, these interventions have the potential to
      decrease the significant overall healthcare costs associated with depression.

PMID- 18041868
TI  - Depression: the benefits of early and appropriate treatment.
AB  - Depression has a profound impact on patient health, individual and family quality
      of life, activities of daily living, and daily functioning, as well as on
      healthcare providers, payers, and employers. Persons with depression tend to have
      multiple comorbidities that compound the negative effects and increase costs. The
      economic burden of the disease is significant, with direct medical costs
      estimated at $3.5 million per 1000 plan members with depression. Depression is
      significantly underdiagnosed and undertreated, particularly in primary care where
      the majority of patients with depression seek care. Effective strategies to
      achieve remission have been identified and have proven effective in clinical
      trials. Early detection, intervention, and appropriate treatment can promote
      remission, prevent relapse, and reduce the emotional and financial burden of the
      disease.

PMID- 18041869
TI  - HEDIS antidepressant medication management measures and performance-based
      measures: an opportunity for improvement in depression care.
AB  - Using the Health Plan Employer Data and Information Set (HEDIS), the National
      Committee for Quality Assurance partners with more than 90% of the nation's
      managed care organizations to collect, audit, and report performance on a range
      of standardized healthcare quality measures. Many HEDIS measures have been useful
      in promoting population health, such as rate of beta-blocker use after myocardial
      infarction or rate of cervical cancer screening. Other measures, such as those
      for Antidepressant Medication Management (AMM), have been less successful.
      Several trends are occurring within behavioral health management that attempt to
      improve depression treatment outcomes, including the implementation of
      performance-based initiatives using the HEDIS AMM measures and the 9-item Patient
      Health Questionnaire. Ultimately, linking quality measures to clinical strategies
      is critical for achieving successful depression treatment outcomes.

PMID- 18041870
TI  - Current landscape of insomnia in managed care.
AB  - Insomnia affects a large percentage of the population, particularly the elderly.
      Literature reports varying estimates of prevalence, a variation that relates to
      the lack of definition and consistency in diagnostic criteria. Primary insomnia
      (not caused by known physical/mental conditions) responds to pharmacologic
      therapy, while secondary insomnia(resulting from other illnesses, medications, or
      sleep disorders) responds to pharmacologic and psychologic treatments (cognitive
      therapy, relaxation techniques, stimulus control). Use of certain agents in the
      elderly and patients with abuse/addiction potential is a concern. Medicare Part D
      does not cover benzodiazepines (classified as controlled substances).
      Nonprescription agents are affordable but have sedation and anticholinergic side
      effects. Medication use should be considered a possible contributing factor.
      Insomnia patients experience significantly more limited activity and higher total
      health services than those without insomnia. Annual costs are between $92.5
      billion and $107.5 billion. A standard definition and better pathways to
      recognize and treat insomnia are needed.

PMID- 18041871
TI  - The state of insomnia and emerging trends.
AB  - Recent research into the pathophysiology of insomnia has brought a shift in the
      approach to treatment. Insomnia rarely occurs in isolation and is typically
      comorbid with other conditions. Rather than simply treating the primary disorder,
      whereby symptoms of insomnia may go unaddressed, now there is a push to
      acknowledge the existence of chronic insomnia as a disorder that itself merits
      treatment. This recognition is due to the identification of pathophysiologic
      changes and associated morbidity, which can be substantial. Insomnia patients
      have increased risk for psychiatric disorders, especially depression, anxiety,
      decreased quality of life, increased healthcare utilization and costs,
      drug/alcohol abuse, decreased occupational performance, and increased
      falls/accidents. Current management patterns explore non-nightly or discontinuous
      hypnotic treatment - non-nightly flexible, non-nightly semiflexible, non-nightly
      fixed, and flexible timing - which deviates from past trends of continuous dosing
      with hypnotics. These trends reflect a change from considering insomnia a symptom
      to treating insomnia as a disorder.

PMID- 18041872
TI  - Chronic insomnia treatment and Medicare Part D: implications for managed care
      organizations.
AB  - The elderly population is of particular concern with regard to insomnia and
      managed care. Early intervention and management of insomnia as a chronic disease
      are recommended. Increased awareness of the negative clinical and economic
      consequences associated with not treating insomnia may serve to raise the
      perceived importance of having effective formulary options for this disease area.
      Because the elderly population is now covered by Medicare Part D, health plans
      previously without a Medicare drug benefit must now select and reimburse for
      sedative-hypnotics for the elderly. A review of the major Medicare Part D plans'
      formularies reveals they offer a limited number of sedative-hypnotic
      alternatives, but not all are available. Due to variable response, variation in
      comorbidities, drug and disease interactions, and individual patient needs,
      managed care organizations should cover a reasonable array of drugs. This is
      essential to optimally manage patients with chronic insomnia to reduce the long
      term clinical morbidity and economic consequences.

PMID- 18041873
TI  - Circadian rhythmicity and the pharmacologic management of insomnia.
AB  - The circadian clock modulates timing of sleep and wakefulness. In certain
      situations, the circadian potentiation of wakefulness may interfere with desired
      sleep-scheduling, particularly in the elderly and shift workers. Known
      abnormalities of circadian regulation are defined by their impact on sleep-wake
      state expression. In delayed sleep phase syndrome, patients have trouble going to
      sleep and arising at reasonable hours and are alert in the evening and sleepy in
      the morning. Patients with advanced sleep phase syndrome are sleepy in the
      evening and awaken very early and alert in the morning. In shift-work sleep
      disorder, individuals attempt to wake and sleep out of phase with the circadian
      clock. As with jet lag, the clock is functioning normally, but the requirements
      on the clock are abnormal. Typical insomnia can also be associated with circadian
      rhythm alterations. Practice guidelines and clinical studies data are needed to
      lead appropriate therapy selection and effective management.

PMID- 18041874
TI  - Patient identification.
AB  - The homeostatic sleep drive and circadian arousal, each opposing the other, form
      the neurobiological bases of the sleep and wake states. Many factors can and do
      disrupt this cycle. Yet, excessive daytime sleepiness is not only common, and it
      often goes unrecognized. It can contribute to accidents, produce or exacerbate
      health conditions, reduce efficiency and productivity, interfere with social
      relationships, and diminish quality of life. The spectrum of common sleep
      disorders includes circadian rhythm changes, shiftwork requirements, obstructive
      sleep apnea, narcolepsy, and difficulty in initiating or maintaining sleep, also
      known as insomnia. In many cases, however, sleep deprivation is the choice of the
      patient, chosen in response to long commutes, academic rigor, or occupational
      matters. Regardless of the sleep disorder that a patient has, good sleep behavior
      or "sleep hygiene" is essential.

PMID- 18041875
TI  - Patient-management strategies.
AB  - An active cortex is necessary for intact cognitive function. In a sleepy
      individual, the cerebral cortex is to some extent deactivated; a sleep-deprived
      person will experience reduced physical and mental activity and productivity,
      more errors on the job, more risk for motor vehicle accidents, and psychosocial
      problems. Hormone levels can become imbalanced from excessive daytime sleepiness
      (EDS), and treatments for conditions unrelated to EDS can be hampered. Whether
      sleep restriction is voluntary or not, those who experience it habitually are at
      greater risk of obesity and type 2 diabetes. While an accurate history is
      necessary to diagnose sleep disorders, all too often a patient's chronic daytime
      sleepiness is never mentioned. EDS will not show up in most blood chemistries
      either. It is important that primary care providers ask patients about their
      sleep and its quality. Other screening tools include questionnaires, which are
      easily administered and can be sensitive. To determine the basis of EDS, formal
      sleep studies may be necessary.

PMID- 18041876
TI  - Managed care considerations.
AB  - Managed care issues arising from excessive daytime sleepiness (EDS), which
      impacts as many as 37% of adults, are widespread. In the United States, insomnia
      is among the 3 most common complaints. Often it is younger people who have
      difficulty falling asleep, whereas their elders report more difficulty remaining
      asleep. Currently, people in the United States sleep 25% fewer hours than they
      did 100 years ago. Chronic sleep deprivation may be a choice driven by economic
      or social factors. Industrialized countries engage about 20% of the work force in
      shifts, and people working night shifts are thought to average 8 fewer hours of
      sleep each week than day workers. Falling asleep behind the wheel is the single
      most imminent risk associated with excessive sleepiness.

PMID- 18041877
TI  - Screening for bipolar disorder.
AB  - Bipolar disorder is a recurrent and sometimes chronic illness involving episodes
      of depression and mania or hypomania. The most frequent presentation is
      depression: more than 1 of 5 primary care patients with depression have bipolar
      disorder. The symptoms of bipolar depression often differ from those of unipolar
      depression. Age of onset for bipolar disorder is usually the late teens; slightly
      older for bipolar II subtype. Nearly all patients with bipolar disorder suffer
      from a comorbid psychiatric disorder, most frequently an anxiety disorder.
      Although the most dramatic presentation of bipolar disorder is the acutely manic
      patient who presents to the emergency department, this presentation is much less
      frequently encountered in physicians' offices, both primary care and psychiatric.
      Bipolarity is often missed in these situations. About half of bipolar patients
      have consulted 3 or more professionals before receiving a correct diagnosis, and
      the average time to first treatment is 10 years. It is imperative that clinicians
      carefully assess patients for bipolar disorder, especially those presenting with
      depression. In addition to patient and family history, administration of a
      screening instrument can be very helpful. The most widely used screening tool is
      the Mood Disorder Questionnaire. This screening tool will be discussed in this
      article regarding its use in outpatient clinics and the community.

PMID- 18041878
TI  - Metabolic syndrome and mental illness.
AB  - Patients with mental illnesses such as schizophrenia and bipolar disorder have an
      increased prevalence of metabolic syndrome and its components, risk factors for
      cardiovascular disease and type 2 diabetes. Although the prevalence of obesity
      and other risk factors such as hyperglycemia are increasing in the general
      population, patients with major mental illnesses have an increased prevalence of
      overweight and obesity, hyperglycemia, dyslipidemia, hypertension, and smoking,
      and substantially greater mortality, compared with the general population.
      Persons with major mental disorders lose 25 to 30 years of potential life in
      comparison with the general population, primarily due to premature cardiovascular
      mortality. The causes of increased cardiometabolic risk in this population can
      include nondisease-related factors such as poverty and reduced access to medical
      care, as well as adverse metabolic side effects associated with psychotropic
      medications, such as antipsychotic drugs. Individual antipsychotic medications
      are associated with well-defined risks of weight gain and related risks for
      adverse changes in glucose and lipid metabolism. Based on the medical risk
      profile of persons with major mental illnesses, and the evidence that certain
      medications can contribute to increased risk, screening and regular monitoring of
      metabolic parameters such as weight (body mass index), waist circumference,
      plasma glucose and lipids, and blood pressure are recommended to manage risk in
      this population. Treatment decisions should incorporate information about medical
      risk factors in general and cardiometabolic risk in particular. In addition to
      the implications for individual clinicians, the problem of disparity in meeting
      healthcare needs for persons with mental illness in comparison with the general
      population has become an important public policy concern, with recent
      recommendations from the National Association of State Mental Health Program
      Directors and the Institute of Medicine. This article provides an overview of
      cardiometabolic risk in patients with major mental illness and describes steps
      for risk reduction.

PMID- 18041879
TI  - Treatment of bipolar disorder: the evolving role of atypical antipsychotics.
AB  - Management of bipolar disorder (BPD) may require multiple medications, including
      lithium, anticonvulsants, and antipsychotics (both conventional and atypical).
      Updated treatment guidelines reflect an expanded role for atypical antipsychotics
      (AAPs) in BPD treatment. Five AAPs--olanzapine, risperidone, quetiapine,
      ziprasidone, and aripiprazole--are approved by the US Food and Drug
      Administration (FDA) as monotherapy for first-line treatment of acute manic and
      (except for quetiapine) mixed episodes. Two AAPs--olanzapine (in fixed-dose
      combination with fluoxetine) and quetiapine--are also FDA approved for bipolar
      depression. For long-term maintenance therapy, one option is to continue
      effective, well-tolerated acute phase treatment; however, only olanzapine and
      aripiprazole are FDA approved for maintenance, based on evidence from randomized,
      placebo-controlled clinical trials. Although head-to-head comparisons are scarce,
      meta-analysis data suggest that olanzapine, risperidone, quetiapine, ziprasidone,
      and aripiprazole have similar antimanic efficacy; therefore, AAP selection for
      this indication should be guided by other considerations such as safety,
      tolerability, and cost. Safety and tolerability issues to consider when selecting
      an AAP include metabolic dysfunction (weight gain, type 2 diabetes, and
      dyslipidemia); hyperprolactinemia; extrapyramidal symptoms; QTc prolongation; and
      pharmacokinetic drug interactions.

PMID- 18041880
TI  - Putting new disease-modifying antirheumatic drugs into perspective.

PMID- 18041881
TI  - Daptomycin versus vancomycin for complicated skin and skin structure infections:
      clinical and economic outcomes.
AB  - STUDY OBJECTIVE: To assess the effect of daptomycin compared with vancomycin on
      the clinical and economic outcomes in patients with complicated skin and skin
      structure infections. DESIGN: Prospective, open-label study. SETTING: Level 1
      trauma center in Detroit, Michigan. PATIENTS: Fifty-three adult patients with
      complicated skin and skin structure infections at risk for methicillin-resistant
      Staphylococcus aureus (MRSA) infection who were treated with daptomycin and a
      matched cohort of 212 patients treated with vancomycin. INTERVENTION: Patients in
      the prospective arm received intravenous daptomycin 4 mg/kg every 24 hours for at
      least 3 days but not more than 14 days. Historical controls received at least 3
      days of vancomycin dosed to achieve trough concentrations of 5-20 microg/ml.
      MEASUREMENTS AND MAIN RESULTS: Outcomes evaluated included blinded assessments of
      clinical resolution, duration of therapy, and costs. The most common diagnoses
      were cellulitis (31%), abscess (22%), and both cellulitis with abscess (37%).
      Microbiology differed significantly between groups, with S. aureus found in 27
      patients (51%) in the daptomycin group and 167 patients (79%) in the vancomycin
      group and MRSA in 22 (42%) and 159 (75%), respectively (p<0.001). The proportions
      of patients with clinical improvement or resolution of their infections on days 3
      and 5 were 90% versus 70% and 98% versus 81% in the daptomycin versus vancomycin
      groups, respectively (p<0.01 for both comparisons), and 100% at the end of
      therapy in both groups. Among patients with complete resolution of their
      infections (41 patients [77%] with daptomycin vs 89 patients [42%] with
      vancomycin, p<0.05), median duration of intravenous therapy was 4 and 7 days,
      respectively, (p<0.001), and hospital costs were $5027 and $7552 (p<0.001).
      CONCLUSIONS: Patients receiving daptomycin achieved more rapid resolution of
      symptoms and clinical cure and had a decreased duration of inpatient therapy
      compared with those receiving vancomycin. This study suggests that daptomycin is
      a cost-effective alternative to vancomycin for complicated skin and skin
      structure infections.

PMID- 18041882
TI  - Impact of previous statin and angiotensin II receptor blocker use on mortality in
      patients hospitalized with sepsis.
AB  - STUDY OBJECTIVE: To examine the effect of previous outpatient use of 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors (statins) and/or angiotensin II
      receptor blockers (ARBs) on 30-day mortality in patients hospitalized with
      sepsis. DESIGN: Retrospective national cohort study. DATA SOURCE: Department of
      Veterans Affairs (VA) national patient care and pharmacy databases. PATIENTS: A
      total of 3018 patients who were hospitalized with sepsis in fiscal year 2000, had
      at least 1 year of previous VA outpatient care, and had at least one active and
      filled VA prescription within 90 days of admission. MEASUREMENTS AND MAIN
      RESULTS: The primary outcome was 30-day mortality. The primary analysis was a
      multilevel model with hospital as a random effect and control variables that
      included comorbid conditions, demographics, and other drugs. Among the 3018
      patients hospitalized with sepsis, mean age was 74.4 years, 2975 (98.6%) were
      male, and 811 (26.9%) died within 30 days of admission. Regarding prescription
      drug use, 480 patients (15.9%) were taking statins and 107 (3.5%) were taking
      ARBs. After adjusting for potential confounders, statin use (odds ratio [OR]
      0.48, 95% confidence interval [CI] 0.36-0.64) and ARB use (OR 0.42, 95% CI 0.24
      0.76) were significantly associated with decreased 30-day mortality. CONCLUSIONS:
      Use of statins and/or ARBs before admission was associated with decreased
      mortality in patients hospitalized with sepsis. Further research is needed to
      determine if these drugs might be started on admission for those with sepsis.

PMID- 18041883
TI  - Pharmacokinetics of oral posaconazole in allogeneic hematopoietic stem cell
      transplant recipients with graft-versus-host disease.
AB  - STUDY OBJECTIVE: To analyze the pharmacokinetics of posaconazole administered as
      prophylaxis for invasive fungal infections in recipients of hematopoietic stem
      cell transplants (HSCTs) who have graft-versus-host disease (GVHD). DESIGN:
      Pharmacokinetic analysis in a subset of posaconazole-treated patients from a
      large, multicenter, phase III, randomized, double-blind, double-dummy, parallel
      group trial that compared posaconazole with fluconazole. SETTING: Ninety
      international medical centers. PATIENTS: The subset of patients comprised 246
      HSCT recipients for whom pharmacokinetic data were available. INTERVENTION: All
      patients received posaconazole 200 mg oral suspension 3 times/day for a maximum
      of 16 weeks. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected after
      dosing on day 2; at weeks 2, 4, 8, and 12; and on the last day of oral treatment.
      After patients had received posaconazole for at least 7 days (i.e., after
      achieving steady state), both maximum observed posaconazole concentration
      (C(max)) and average posaconazole concentration (C(av)) were determined. Five
      patients developed invasive fungal infections while receiving treatment. Median
      C(av) and C(max) were 611 and 635 ng/ml, respectively, in these five patients and
      were 922 and 1360 ng/ml, respectively, in the 241 patients without invasive
      fungal infection. In patients without invasive fungal infection, posaconazole
      concentrations were not clinically affected by race, body weight, or age. Median
      plasma posaconazole concentrations were higher in patients with chronic GVHD than
      in those with acute GVHD. In 18 patients without invasive fungal infection who
      experienced diarrhea on the day of sampling, posaconazole concentrations were
      lower than the concentrations in patients without diarrhea. No relationship was
      observed between alanine aminotransferase, aspartate aminotransferase, or
      bilirubin levels and posaconazole concentrations. CONCLUSION: Posaconazole 200 mg
      3 times/day resulted in median plasma drug concentrations sufficiently high to
      prevent invasive fungal infections in HSCT recipients with GVHD, without
      compromising patient safety. Plasma posaconazole concentrations are generally
      unaffected by demographic variables, including race, sex, body weight, and age.

PMID- 18041884
TI  - Clinical outcomes and cost minimization with an alternative dosing regimen for
      meropenem in a community hospital.
AB  - STUDY OBJECTIVE: To compare outcomes and cost for the traditional United States
      Food and Drug Administration-approved dosing regimen for meropenem versus an
      alternative dosing regimen providing similar pharmacodynamic exposure with a
      lower total daily dose. DESIGN: Retrospective cohort study with a cost
      minimization analysis. SETTING: A 417-bed, privately owned community hospital.
      PATIENTS: One hundred patients who received meropenem 1 g every 8 or 12 hours
      (traditional dosing regimen) between January 1 and September 30, 2004 (historical
      controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours
      (alternative dosing regimen) between October 1, 2004, and September 30, 2005.
      MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data were collected for
      all patients. Cost-minimization analysis was performed by using the drug
      acquisition cost for meropenem. Demographics, sources of infection, distributions
      of organisms, and Charlson Comorbidity Index scores were similar between patients
      in the traditionally and alternatively dosed groups. Concomitant therapy,
      duration of therapy, success rates, lengths of stay, and in-hospital mortality
      rates were also similar between groups. Median time to the resolution of symptoms
      was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001).
      A logistic regression model including the dosing strategy showed that only
      polymicrobial infections and sepsis were associated with increased failure rates.
      The median cost for antibiotics was $439.05/patient for traditional dosing and
      $234.08/patient for alternative dosing (p<0.0001). CONCLUSION: An alternative
      dosing regimen for meropenem with a lower total daily dose yielded patient
      outcomes, including success rates and duration of therapy, equivalent to those of
      the traditional dosing regimen. Alternative dosing decreased total drug exposure,
      costs for antibiotics, and time to the resolution of infections.

PMID- 18041885
TI  - Caspofungin as primary antifungal prophylaxis in stem cell transplant recipients.
AB  - STUDY OBJECTIVES: To assess the effectiveness and tolerability of caspofungin as
      primary prophylaxis against invasive fungal infections in stem cell transplant
      recipients who are poor candidates for triazole or lipid amphotericin B
      prophylaxis due to renal or hepatic dysfunction, and to determine whether any
      patient characteristics are independently associated with an increased risk of
      breakthrough invasive fungal infection during caspofungin prophylaxis. DESIGN:
      Retrospective medical record review. SETTING: Tertiary care comprehensive cancer
      center. PATIENTS: One hundred twenty-three adult stem cell transplant recipients
      who received caspofungin 35-50 mg/day for up to 100 days after transplantation as
      primary antifungal prophylaxis between January 1, 2002, and June 30, 2005.
      MEASUREMENTS AND MAIN RESULTS: Data were collected on host and transplant
      characteristics such as transplant type, neutropenia, graft-versus-host disease
      (GVHD), and corticosteroid use, as well as evidence of breakthrough invasive
      fungal infections. Of the 123 patients, 117 (95.1%) were allogeneic recipients,
      and the median time to engraftment was 12 days (range 6-26 days). Fifty (40.7%)
      of the patients developed GVHD of grade 2 or greater and received corticosteroids
      for more than 21 days. Median duration of caspofungin prophylaxis was 73 days
      (range 10-100 days). Nine patients (7.3%) developed breakthrough invasive fungal
      infections (two cases of mixed Aspergillus species and one each of Aspergillus
      terreus, Rhizopus, Exserohilum, an unspecified mold, Cryptococcus, Candida
      glabrata, and Candida tropicalis). Median time to invasive fungal infection
      development was 65 days (range 12-88 days). Only one case occurred during the
      neutropenic period before engraftment. Multivariate analysis showed that
      Pseudomonas coinfection (p=0.04) and infliximab therapy (p=0.02) were associated
      with breakthrough invasive fungal infections in patients receiving caspofungin.
      By day 100, there were five (4.1%) deaths, two of which were directly
      attributable to invasive fungal infections. No caspofungin-related adverse events
      were reported. CONCLUSION: Caspofungin seems to be an effective and well
      tolerated option for primary antifungal prophylaxis in the highly
      immunosuppressed stem cell transplant patient population.

PMID- 18041886
TI  - Clinical decision support tools: performance of personal digital assistant versus
      online drug information databases.
AB  - STUDY OBJECTIVES: To evaluate personal digital assistant (PDA) drug information
      databases used to support clinical decision-making, and to compare the
      performance of PDA databases with their online versions. DESIGN: Prospective
      evaluation with descriptive analysis. METHODS: Five drug information databases
      available for PDAs and online were evaluated according to their scope (inclusion
      of correct answers), completeness (on a 3-point scale), and ease of use; 158
      question-answer pairs across 15 weighted categories of drug information essential
      to health care professionals were used to evaluate these databases. An overall
      composite score integrating these three measures was then calculated. Scores for
      the PDA databases and for each PDA-online pair were compared. RESULTS: Among the
      PDA databases, composite rankings, from highest to lowest, were as follows: Lexi
      Drugs, Clinical Pharmacology OnHand, Epocrates Rx Pro, mobileMicromedex (now
      called Thomson Clinical Xpert), and Epocrates Rx free version. When we compared
      database pairs, online databases that had greater scope than their PDA
      counterparts were Clinical Pharmacology (137 vs 100 answers, p<0.001), Micromedex
      (132 vs 96 answers, p<0.001), Lexi-Comp Online (131 vs 119 answers, p<0.001), and
      Epocrates Online Premium (103 vs 98 answers, p=0.001). Only Micromedex online was
      more complete than its PDA version (p=0.008). Regarding ease of use, the Lexi
      Drugs PDA database was superior to Lexi-Comp Online (p<0.001); however, Epocrates
      Online Premium, Epocrates Online Free, and Micromedex online were easier to use
      than their PDA counterparts (p<0.001). In terms of composite scores, only the
      online versions of Clinical Pharmacology and Micromedex demonstrated superiority
      over their PDA versions (p>0.01). CONCLUSION: Online and PDA drug information
      databases assist practitioners in improving their clinical decision-making. Lexi
      Drugs performed significantly better than all of the other PDA databases
      evaluated. No PDA database demonstrated superiority to its online counterpart;
      however, the online versions of Clinical Pharmacology and Micromedex were
      superior to their PDA versions in answering questions.

PMID- 18041887
TI  - Ranolazine: a new option in the management of chronic stable angina.
AB  - Pharmacotherapy for the management of chronic stable angina has not changed much
      in the past 10-20 years. Although the use of revascularization has increased,
      beta-blockers, calcium channel blockers, and long-acting nitrates are still
      widely used in the management of patients with chronic stable angina. Despite the
      demonstrated effectiveness of these agents, a number of patients do not achieve
      the American College of Cardiology-American Heart Association goal of freedom
      from exertional angina attacks. For the first time in more than a decade, a new
      agent, ranolazine, is available to assist in controlling exertional angina.
      Ranolazine has a novel mechanism of action of inhibiting the late sodium current
      during ventricular depolarization. This mechanism contributes to a reduction in
      intracellular sodium and, therefore, a reduction in intracellular calcium,
      reducing ischemic injury. Unlike currently available pharmacotherapy for chronic
      stable angina, ranolazine does not produce clinically meaningful changes in heart
      rate or blood pressure. A number of clinical trials have demonstrated the ability
      of ranolazine to increase exercise tolerance, decrease weekly anginal episodes,
      and decrease sublingual nitroglycerin consumption for breakthrough angina. Based
      on the results of these trials, ranolazine recently was approved by the United
      States Food and Drug Administration for treatment of patients with chronic stable
      angina. Because of ranolazine's pharmacokinetic and pharmacodynamic profile,
      pharmacists will have to play a significant role in patient selection and
      monitoring.

PMID- 18041888
TI  - Traditional management of chronic stable angina.
AB  - The clinical syndrome of chronic stable angina is an age-related condition that
      is one common manifestation of coronary artery disease (CAD). The presence of
      angina significantly affects quality of life when patients must limit their
      activities of daily living in an effort to prevent the occurrence of anginal
      attacks. In addition, patients are at risk for significant complications of CAD
      such as myocardial infarction, heart failure, stroke, and death. Therefore,
      treatment should focus not only on relief of symptoms and improvements in quality
      of life, but also on preventing disease progression and reducing the risk of
      complications from CAD. All patients should be instructed on the appropriate use
      of sublingual nitroglycerin for the immediate treatment of anginal episodes. Beta
      blockers, calcium channel blockers, long-acting nitrate therapy, and ranolazine
      can prevent anginal symptoms. In addition, aggressive risk factor management,
      healthy lifestyle changes, antiplatelet agents such as aspirin, and angiotensin
      converting enzyme inhibitors all should be used to prevent disease progression
      and occurrence of myocardial infarction or death. Many patients will be
      candidates for revascularization of the myocardium with either percutaneous
      coronary intervention or coronary artery bypass grafting for relief of symptoms
      as well as improvement in prognosis. Even after revascularization, patients may
      still require antianginal drug therapy. All patients undergoing revascularization
      should be guided to make appropriate lifestyle changes and to make concerted
      efforts to manage risk factors for CAD.

PMID- 18041889
TI  - Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis.
AB  - Rheumatoid arthritis is a chronic autoimmune disease that often leads to
      functional disability and reduced quality of life. The pathogenesis of synovial
      inflammation that is associated with this disease is thought to result from T
      cell activation. To become fully activated, T cells require an antigen-specific
      signal through the T-cell receptor and a second signal through a costimulatory
      receptor. Abatacept is the first drug in a new class of disease-modifying
      antirheumatic drugs (DMARDs) known as selective costimulation modulators.
      Costimulation modulators block the second signal and decrease T-cell activation.
      Abatacept has been approved by the United States Food and Drug Administration for
      reducing signs and symptoms, inducing major clinical response, slowing the
      progression of structural damage, and improving physical function in adults with
      moderate-to-severe active rheumatoid arthritis who have had an inadequate
      response to at least one other DMARD, such as methotrexate or tumor necrosis
      factor (TNF)-alpha inhibitors. Randomized controlled trials have shown that
      abatacept improves both clinical outcomes and health-related quality of life in
      patients who have had an inadequate response to other DMARDs. Abatacept has been
      shown to be well tolerated. In clinical trials, however, abatacept treatment was
      associated with a higher rate of infections compared with placebo. This finding
      was compounded when abatacept was used with TNF-alpha inhibitors; thus, this
      combination should be avoided. Abatacept appears to be a useful treatment option
      for patients with rheumatoid arthritis who have previously failed other DMARDs.
      However, additional clinical trials evaluating its long-term effect on patient
      safety and disease outcomes are needed.

PMID- 18041890
TI  - Rituximab for the treatment of rheumatoid arthritis.
AB  - Rituximab has been approved by the United States Food and Drug Administration in
      combination with methotrexate for the treatment of rheumatoid arthritis in
      patients who failed to achieve adequate benefit from tumor necrosis factor-alpha
      inhibitors. Rituximab is a biologic agent that depletes peripheral B cells--an
      action thought to reduce rheumatoid arthritis activity--and induces prolonged
      clinical improvement. Two 1000-mg infusions administered 2 weeks apart can result
      in a response that lasts for months. Most patients will require retreatment, but
      the effect of repeated dosing on patient outcomes has not yet been determined.
      Combination therapy with methotrexate is recommended as this appears to achieve
      the best outcomes. Rituximab also has been shown to be safe, although the lack of
      long-term efficacy and safety data limit its use. More studies are needed, but
      this agent has been demonstrated to be safe and effective in patients who fail to
      achieve adequate clinical response to methotrexate and tumor necrosis factor
      alpha inhibitors.

PMID- 18041891
TI  - Candida endophthalmitis: focus on current and future antifungal treatment
      options.
AB  - Candida endophthalmitis is a sight-threatening manifestation of disseminated
      candidiasis. The occurrence of endogenous candida endophthalmitis in patients
      with candidemia has ranged from 0-45% in the published literature. In critically
      ill patients, it has even been associated with increased mortality. In recent
      years, use of newer antifungal therapies for invasive candidiasis has increased
      given the rise in infections with non-albicans species of Candida. To identify
      current practices of the management of endogenous candida endophthalmitis and
      relevant antifungal drug research in this disease state, we conducted a MEDLINE
      search (1967-2006) and bibliographic search of the English-language literature.
      Treatments for candida endophthalmitis have not been evaluated through well
      designed, well-powered clinical trials. Data have mainly been presented in case
      reports, case series, animal studies, pharmacokinetic studies, and as small
      subsets of larger trials. Traditional systemic therapies have been amphotericin B
      with or without flucytosine or fluconazole. Cure rates with antifungal drugs
      alone appear to be much higher in patients with chorioretinitis than in
      endophthalmitis with vitreal involvement. Pars plana vitrectomy with or without
      intravitreal amphotericin B injections has been advocated particularly for
      patients with moderate-to-severe vitritis and substantial vision loss.
      Information on new antifungal agents for endophthalmitis is limited, despite
      increasing use in patients with candidemia. Voriconazole may be a particularly
      attractive agent to consider for infections with fluconazole-resistant,
      voriconazole-susceptible strains. The current patchwork of animal studies and
      small patient reports provide clinicians with some insight into the role of newer
      agents in the treatment of candida endophthalmitis. In general, it appears that
      chorioretinitis infections can be more readily cured with most systemic
      antifungal agents, whereas more aggressive treatment, often including vitrectomy
      with or without intra-vitreal antifungal administration, is needed for patients
      with endophthalmitis with vitritis.

PMID- 18041892
TI  - Key articles and guidelines in the management of acute coronary syndromes and in
      percutaneous coronary intervention: 2007 update.
AB  - Clinical evidence in the management of acute coronary syndromes (ACS) and in
      percutaneous coronary intervention (PCI) continues to evolve at a rapid pace. For
      clinicians to provide optimal care for these patients, it is important to keep up
      with new information as it becomes available. With the existence of numerous
      pharmacologic agents, abundance of major clinical trials, and several nationally
      recognized clinical guidelines, compiling the needed reference material to make
      evidence-based decisions on the care of patients with ACS or those undergoing PCI
      can be difficult for clinicians. Therefore, we provide an update to the first
      compiled bibliography of key articles and guidelines relative to patients with
      ACS published in Pharmacotherapy in 2004. A number of guidelines and practice
      changing literature have been published since the initial 2004 document. We hope
      that this compilation will serve as a resource for pharmacists, physicians,
      nurses, residents, and students responsible for the care of patients with
      coronary heart disease.

PMID- 18041893
TI  - Azacitidine-associated hyperthermia and interstitial pneumonitis in a patient
      with myelodysplastic syndrome.
AB  - The DNA hypomethylating agent azacitidine was approved by the United States Food
      and Drug Administration after the drug demonstrated superiority over the best
      supportive care for treatment of myelodysplastic syndrome in patients unable to
      undergo stem cell transplantation. Mild adverse reactions, both hematologic and
      nonhematologic, are not uncommon; however, severe adverse effects are rare. We
      describe a 55-year-old woman who was treated with azacitidine for myelodysplastic
      syndrome and experienced hyperthermia that was not attributable to other causes.
      The patient's treatment course was further complicated by interstitial
      pneumonitis and hypoxic respiratory failure that ultimately led to acute
      respiratory distress syndrome. Hyperthermia develops when discord occurs between
      metabolic heat production and heat dissipation. The process of temperature
      regulation can be altered by drugs such as succinylcholine, phenothiazines,
      monoamine oxidase inhibitors, atropine, benztropine, antihistamines, cocaine,
      Ecstasy, amphetamines, and haloperidol. The hyperthermia in this patient was
      refractory to antipyretic therapy and was not due to other drug-induced
      hyperthermic syndromes. She eventually responded to high-dose methylprednisolone.
      The Naranjo adverse drug reaction probability scale score indicated that the
      association between azacitidine and hyperthermia was probable. Clinicians should
      be aware of this rare, severe, potential adverse effect of azacitidine.

PMID- 18041894
TI  - Nebulized milrinone use in a pulmonary hypertensive crisis.
AB  - Significant advances have been achieved over the past few decades regarding
      comprehension of the pathogenesis of pulmonary arterial hypertension (PAH). The
      development of new agents and use of existing drug therapies have targeted the
      underlying abnormalities and pathways leading to progression of PAH. Milrinone, a
      phosphodiesterase inhibitor, remains a therapeutic option. Unfortunately,
      intravenous administration of the drug in patients with PAH may be limited by
      systemic hypotension, especially in those already receiving prostanoid treatment.
      We describe a 42-year-old woman with acute decompensated idiopathic PAH who was
      given nebulized milrinone as a novel adjunctive therapy. She was acutely treated
      with intravenous treprostinil 2 ng/kg/minute and inhaled nitric oxide 20 ppm.
      However, increasing the treprostinil infusion rate or adding other therapies such
      as intravenous milrinone for acute symptomatic relief was limited by her
      hemodynamic instability, which required treatment with dobutamine, vasopressin,
      and epinephrine. Nebulized milrinone was added as salvage therapy for her acute
      PAH crisis. After 8 days of therapy, the patient's PAH symptoms improved without
      compromising her mean arterial pressure and heart rate. Nebulized milrinone in
      addition to inhaled nitric oxide and low-dose intravenous treprostinil may have
      played a major role in the acute management of her PAH crisis. Further studies
      are needed to assess the role of nebulized milrinone in patients with PAH.

PMID- 18041895
TI  - Mefloquine-induced eosinophilic pneumonia.
AB  - Mefloquine has been widely used for prophylaxis and treatment of patients with
      chloroquine-resistant malaria; the drug is usually well tolerated. Rarely,
      adverse effects may be severe, including gastrointestinal disturbances,
      neuropsychiatric reactions, cardiovascular manifestations, skin lesions,
      musculoskeletal symptoms, and bone marrow toxicity. We describe a 67-year-old
      woman with fever, dyspnea on exertion, peripheral blood eosinophilia, and diffuse
      pulmonary infiltrates on chest radiography. She had taken mefloquine for malaria
      prophylaxis for an 8-week trip to South Africa. A thorough work-up led to the
      diagnosis of eosinophilic pneumonia caused by the mefloquine. Her condition
      improved after the drug was discontinued. To our knowledge, this is the first
      report of mefloquine-induced eosinophilic pneumonia. Clinicians should be aware
      of this rare, potential adverse effect of mefloquine.

PMID- 18041896
TI  - Back to the future: the ribosome as an antibiotic target.

PMID- 18041897
TI  - Longicin plays a crucial role in inhibiting the transmission of Babesia parasites
      in the vector tick Haemaphysalis longicornis.

PMID- 18041899
TI  - Nitazoxanide: clinical studies of a broad-spectrum anti-infective agent.
AB  - Nitazoxanide is a new compound with broad-spectrum activity against numerous
      intestinal protozoa, helminths and anaerobic bacteria. It is approved for the
      treatment of diseases caused by Giardia intestinalis and Cryptosporidium species.
      The drug is well tolerated, with few side effects and requires a short course of
      treatment. Further investigations regarding its use in patients with AIDS is
      needed. Nitazoxanide represents a significant advance in the treatment of
      intestinal parasitic infections worldwide.

PMID- 18041900
TI  - Retapamulin: a semisynthetic pleuromutilin compound for topical treatment of skin
      infections in adults and children.
AB  - Retapamulin is a semisynthetic pleuromutilin compound with in vitroactivity
      against Gram-positive bacteria, no cross-resistance to other classes of
      antimicrobial agents in current use and a low potential for development of
      resistance. A 1% ointment formulation has been developed for clinical use, and a
      placebo-controlled trial of impetigo in 210 patients produced significantly
      higher rates of clinical and microbiological success compared with placebo - 85.6
      versus 52.1% and 91.2 versus 50.9%, respectively. Additional comparative studies
      in over 1900 patients showed noninferiority to topical fusidic acid and oral
      cephalexin and a low frequency of adverse events. In 2007, retapamulin was
      approved in the USA for topical treatment of impetigo caused by Streptococcus
      pyogenes and methicillin-susceptible Staphylococcus aureus, and in the EU for
      topical treatment of impetigo and infected wounds caused by S. pyogenes and S.
      aureus, with approvals including adults and children over 9 months of age.

PMID- 18041901
TI  - Environmental stress regulates Shigella virulence: interplay between anerobiosis
      and iron acquisition.

PMID- 18041902
TI  - Anticancer and immunosuppressive properties of bacterial prodiginines.
AB  - Bacterial prodiginines are a family of red-pigmented, tripyrrolic compounds that
      display numerous biological activities, including antibacterial, antifungal,
      antiprotozoal, antimalarial, immunosuppressive and anticancer properties.
      Recently, significant progress has been made in understanding the biosynthesis
      and regulation of bacterial prodiginines. An understanding of the biosynthesis of
      prodiginines will allow engineering of bacterial strains capable of synthesizing
      novel prodiginines through rational design and mutasynthesis experiments.
      Bacterial prodiginines and synthetic derivatives are effective proapoptotic
      agents with multiple cellular targets, and they are active against numerous
      cancer cell lines, including multidrug-resistant cells, with little or no
      toxicity towards normal cell lines. A synthetic derivative, GX15-070 (Obatoclax),
      developed through structure-activity relationship studies of the pyrrolic ring A
      of GX15, is in multiple Phase I and II clinical trials in both single and dual
      agent studies to treat different types of cancer. Therefore, prodiginines have
      real therapeutic potential in the clinic.

PMID- 18041903
TI  - Methionine sulfoxide reductases and virulence of bacterial pathogens.
AB  - Oxidation of methionine (Met) residues in proteins by reactive oxygen species and
      reactive nitrogen intermediates results in altered protein structures, which
      subsequently affect their functions. Oxidized Met (Met-O) residues are reduced to
      Met by the methionine sulfoxide reductase (Msr) system, which includes mainly
      MsrA and MsrB. MsrA and MsrB show no sequence and structural identity with each
      other but both reduce methionine sulfoxides. MsrA is specific to the reduction of
      methionine-S-sulfoxide, whereas MsrB is specific to the reduction of methionine-R
      sulfoxide. Genes encoding the enzymes MsrA and MsrB exist in most living
      organisms including bacteria. In recent times, absence of these enzymes has been
      implicated in the virulence of bacterial pathogens. In particular, pathogens
      deficient in Msr have been reported to have reduced ability to adhere with
      eukaryotic cells, to survive inside hosts and to resist in vitro oxidative
      stress. Bacterial proteins that are susceptible to Met oxidation, in the absence
      of Msr, have also been identified. This review discusses the current knowledge on
      the role of Msr in bacterial virulence.

PMID- 18041904
TI  - Advances in Tropheryma whipplei research: the rush to find biomarkers for
      Whipple's disease.
AB  - Whipple's disease (WD) is a systemic chronic infection, caused by the Gram
      positive bacterium Tropheryma whipplei. There are several clinical traits linked
      to WD: histological lesions in the GI tract in association with diverse clinical
      manifestations (classic WD), endocarditis with negative blood cultures, and
      isolated neurological infection. WD is rare, predominantly affects middle-aged
      men and is fatal without treatment. The most recent strategy for diagnosing WD
      uses the results of diastase-resistant periodic acid Schiff staining and PCR in
      parallel, both performed on involved organ/tissue biopsy (small intestine,
      cardiac valve and cerebrospinal fluid). The generation of rabbit polyclonal
      antibodies has enabled the detection of the bacterium in tissues by
      immunohistochemical staining. However, the diagnosis of WD remains an invasive
      procedure. The recent achievement of stable bacterial culture and sequencing of
      the T. whipplei genome has opened a framework for the development of a biomarker
      platform. Several studies in different fields have been performed, for example,
      transcriptomics, immunoproteomics and comparative proteomics. Biomarker
      candidates have been proposed for the development of less invasive procedures for
      diagnosing WD.

PMID- 18041905
TI  - Candidate targets for new antivirulence drugs: selected cases of bacterial
      adhesion and biofilm formation.
AB  - Management of bacterial infections is becoming increasingly difficult due to the
      rising frequency of strains that are resistant to many current antibiotics. New
      types of antibiotics are, therefore, urgently needed. Virulence factors or
      virulence-associated phenotypes such as adhesins and biofilm formation are highly
      attractive targets for new drugs. Specific adhesion provides bacteria with target
      selection and prevents removal by hydrodynamic flow forces. Bacterial adhesion is
      of paramount importance for bacterial pathogenesis. Adhesion is also the first
      step in biofilm formation. Biofilm formation is particularly problematic in
      medical contexts because biofilm-associated bacteria are particularly hard to
      eradicate. Several promising candidate drugs that target bacterial adhesion and
      biofilm formation are being developed. Some of these might be valuable weapons
      for fighting infectious diseases in the future. Here we use illustrative
      examples, mainly from the enterics, to demonstrate the principles.

PMID- 18041906
TI  - Novel targets for antibiotics in Staphylococcus aureus.
AB  - Multiple resistant staphylococci that cause significant morbidity and mortality
      are the leading cause of nosocomial infections. Meanwhile, methicillin-resistant
      Staphylococcus aureus (MRSA) also spreads in the community, where highly virulent
      strains infect children and young adults who have no predisposing risk factors.
      Although some treatment options remain, the search for new antibacterial targets
      and lead compounds is urgently required to ensure that staphylococcal infections
      can be effectively treated in the future. Promising targets for new
      antibacterials are gene products that are involved in essential cell functions.
      In addition to antibacterials, active and passive immunization strategies are
      being developed that target surface components of staphylococci such as cell wall
      linked adhesins, teichoic acids and capsule or immunodominant antigens.

PMID- 18041907
TI  - Use of animal models in the development of human vaccines.
AB  - Over the past 100 years, animal infectious disease research has played a crucial
      role in the development of human vaccines. In fact, many of today's vaccines are
      based on utilizing animal pathogens, either in the form of an attenuated vaccine
      or as a vaccine vector. Vaccine development has become increasingly complex with
      chronic and newly emerging diseases, a demand for therapeutic vaccines for
      noninfectious diseases, extended vaccine in the neonate and the elderly, and
      increasing concerns regarding vaccine safety. Furthermore, the evaluation of
      quantity and quality of immune responses and the ability to efficiently translate
      the results of basic research into the clinic are critical to ensure that
      vaccines meet their therapeutic potential. Here, we review the importance of
      animal models for developing and testing novel human vaccines, discuss the
      limitations of existing animal models in knowledge translation, and summarize the
      needs and criteria for future animal models. We argue that efficient translation
      of basic vaccine research to clinical therapies will depend upon the availability
      of appropriate animal models to address each of the questions which arise during
      vaccine development.

PMID- 18041908
TI  - Investigating novel therapeutic targets and molecular mechanisms to treat
      botulinum neurotoxin A intoxication.
AB  - Botulinum neurotoxin (BoNT) has recently catapulted into the public consciousness
      in two seemingly disparate roles: potential use as a biological weapon and
      treatment of neuromuscular disorders. This bacterially produced protein is the
      most potent toxin known to humans, with a lethal dose estimated at approximately
      1 ng/kg of body weight. BoNT intoxication occurs via a multistep process that
      includes recognition of peripheral neuronal cell membrane receptors, endocytosis
      and translocation of the light chain metalloprotease into the cytosol, and
      catalytic cleavage of soluble N-ethylmaleimide-sensitive factor attachment
      protein receptor (SNARE) proteins critical for vesicle fusion and
      neurotransmitter release. Each of these distinct steps has been studied at the
      molecular level and is a valid target for the development of pharmacological
      interventions to prevent the considerable mortality associated with botulism.
      Alternatively, clinical uses of BoNT continue to expand at an ever-increasing
      rate; however, further optimization of BoNT therapy is critical to maximize
      efficacy.

PMID- 18041909
TI  - Anatomical location of urothelial carcinomas of the urinary tract leads to
      perspectives of specific treatment.

PMID- 18041911
TI  - 17th World Congress of the International Association of Surgeons,
      Gastroenterologists and Oncologists.

PMID- 18041912
TI  - Expression profiling of melanoma cell lines: in search of a progression-related
      molecular signature.

PMID- 18041913
TI  - Significance of whole-pelvic radiotherapy for high-risk prostate cancer patients
      after radical prostatectomy.

PMID- 18041914
TI  - Lung cancer susceptibility: are we on our way to identifying a high-risk group?
AB  - Many studies have investigated lung cancer susceptibility based on the presence
      of low-penetrance, high-frequency single nucleotide polymorphisms. Identifying
      such susceptibility polymorphisms may lead to the development of tests that allow
      a more focused follow-up of a high-risk group. Genetic polymorphisms of
      xenobiotic metabolism, DNA repair, cell-cycle control, immunity, addiction and
      nutritional status have been described as promising candidates. Genetic
      polymorphisms in both metabolic activation (Phase I) and detoxification (Phase
      II) enzymes influence DNA damage. The DNA repair system is a critical cellular
      response that counteracts the carcinogenic effects of DNA. Thus, genetically
      determined susceptibility to carcinogens depends on the balance between metabolic
      and DNA repair enzymes. This review evaluates whether or not a specific
      polymorphism or a combination of such polymorphisms can effectively predict high
      risk groups.

PMID- 18041915
TI  - Molecular approaches to resolve diagnostic dilemmas: the case of gastrointestinal
      stromal tumor and leiomyosarcoma.
AB  - Gastrointestinal stromal tumors (GISTs) and leiomyosarcomas (LMSs) are common
      types of mesenchymal tumors that may present a diagnostic challenge. GISTs have
      frequent overexpression of Kit and often encode for mutation of the KIT oncogene.
      In addition, patients usually experience a favorable response to targeted therapy
      with imatinib mesylate (Gleevec, STI-571), but not cytotoxic chemotherapy. Up to
      5% of GISTs can be completely negative for Kit on immunohistochemistry.
      Conversely, LMSs may rarely express Kit, but are virtually never associated with
      an activating KIT mutation, and are often effectively treated with cytotoxic
      chemotherapy but are resistant to imatinib. To aid in resolution of this clinical
      challenge, we performed a whole-genome gene expression study on 71 well-defined
      GIST and LMS samples with development of a robust, novel approach to molecular
      classification discussed herein.

PMID- 18041916
TI  - PI3 kinase/AKT pathway as a therapeutic target in multiple myeloma.
AB  - The development of novel therapies for multiple myeloma depends on a
      comprehensive understanding of the events leading to cellular proliferation and
      survival. Controlling pathways that regulate growth signals is an emerging and
      complementary approach to myeloma treatment. The PI3K/Akt pathway is a central
      gatekeeper for crucial cellular functions including adhesion, angiogenesis,
      migration and development of drug resistance. Established proteins and genes such
      as mTOR, p53, NF-kappaB and BAD are all regulated through PI3K and Akt
      activation, making them attractive targets for broad downstream effects. Direct
      PI3K inhibition has demonstrated impressive tumor inhibition and regression in
      cell-line and animal models, and multiple agents including SF1126 are currently
      in clinical trials. Drugs such as perifosine that are specific for Akt are also
      in development. Combinations of these agents with existing therapies are rational
      approaches on the path to improving myeloma treatment.

PMID- 18041917
TI  - Reducing biochemical recurrence rates in EBRT-treated prostate cancer patients:
      the influence of dose and dose per fraction.
AB  - In the last 15-20 years, technological improvements in radiation treatment
      planning and delivery have allowed radiation oncologists to increase the total
      dose to the prostate gland. The results of four randomized trials using
      conventional daily doses (1.8-2 Gy) demonstrate that higher total doses lead to
      lower rates of biochemical recurrence, but with a modest increase in late
      toxicity. Preclinical data suggest that treatment schedules relying on fewer,
      larger daily fractions of radiotherapy (hypofractionation) may increase the
      therapeutic ratio. Early results from several uncontrolled trials indicate that
      schedules that rely on larger daily doses are associated with low toxicity,
      provided some form of daily target localization and sophisticated treatment
      delivery are used. The results of several randomized trials that compare
      hypofractionated regimens to conventionally fractionated regimens will be
      available in the next 5-10 years.

PMID- 18041918
TI  - Lentiviral vector-mediated RNAi and its use for cancer research.
AB  - RNAi is a useful tool for functional analysis of genes and developing a potential
      therapeutic strategy for various diseases including cancers. RNAi can be applied
      in various forms. HIV vectors are useful for the stable transduction of genes to
      both replicating and quiescent cells with a broad host tropism, and have been
      developed for basic and clinical research of gene therapy. HIV vectors can
      deliver shRNAs for post-transcriptional silencing of specific genes with high
      efficiency, and have been used to evaluate various genes for their potential
      involvement in cancer development and malignant features, and may be useful for
      future cancer gene therapy. Here we describe the development of shRNA-expressing
      HIV vectors and their use in cancer research, as well as perspectives for their
      future use in cancer gene therapy.

PMID- 18041919
TI  - Constitutional polymorphisms of prostate cancer: prognostic and diagnostic
      implications.
AB  - Prostate cancer is the most common cancer diagnosis in men. While often perceived
      as a slow, indolent malignancy, prostate cancer trails only lung cancer among
      cancer-related mortality in men. Current diagnosis and treatment algorithms are
      plagued by overdiagnosis of non-lethal indolent prostate cancer with no proven
      means to predict, detect, and prevent aggressive lethal prostate cancer in men
      most at risk. These challenges are particularly concerning for African-American
      men who demonstrate increased rates of prostate cancer incidence and mortality
      when compared to other ethnic groups. With the completion of the human genome
      project, technology and techniques now exist to differentiate cancer from normal
      tissues based on the expression patterns of thousands of genes assessed
      simultaneously on a single microarray gene 'chip'. This platform has greatly
      improved our understanding of genes that regulate tumor behavior once cancer is
      established. Microarrays can also be utilized in patients without cancer to
      determine which patients are at high risk for tumor development and in need of
      rational prevention strategies. Constitutional single nucleotide polymorphisms
      (SNPs) are one source of genetic variation and may serve as a means to identify
      these high-risk individuals. SNPs are single nucleotide base pair changes within
      a gene which occur in one percent or more of the population. SNPs can contribute
      to a disease state by altering the function of a protein encoded by a gene
      without affecting gene expression. This review will examine the current
      understanding of constitutional SNPs associated with prostate cancer
      carcinogenesis, highlight two current diagnostic array platforms and discuss
      implications for future prevention and screening programs.

PMID- 18041920
TI  - An interview with Robert Tanguay, Ph.D. Interviewed by Vicki Glaser.

PMID- 18041921
TI  - The Time Reaper 5-Channel Automatic Liquid Dispenser: a new tool for studying
      zebrafish development.
AB  - Patterning of zebrafish and other vertebrate embryos proceeds according to
      consistent, predictable developmental time courses. Because zebrafish spawn
      primarily during the first few hours after dawn, many important developmental
      stages typically occur during the middle of the night. As an automatic, accurate
      way to fix embryos at these inconvenient times, we have developed the Time Reaper
      5-Channel Automatic Liquid Dispenser (TimeR). The TimeR delivers up to 50 mL of
      liquid to embryos in a Petri dish at preset times. We have used the TimeR to
      deliver paraformaldehyde and fix zebrafish embryos at different stages of
      development. We find that the pattern of expression for a number of genes is
      indistinguishable between embryos fixed manually and with the TimeR. The TimeR is
      also suitable for fixing embryos for whole-mount immunostaining, but care needs
      to be taken to find conditions that preserve the antibody's epitope. The TimeR is
      inexpensive to make, and can be constructed using tools present in most machine
      shops. In addition to fixing embryos, the TimeR will be useful for any experiment
      that requires automatic delivery of milliliter amounts of liquid.

PMID- 18041922
TI  - The zebrafish fgf family.
AB  - Fibroblast growth factors (FGFs) are secreted polypeptide growth factors. The FGF
      signaling system plays crucial roles in multiple developmental processes in
      vertebrates. The human FGF family comprises 22 members. Although 16 zebrafish
      fgfs have been reported, the zebrafish fgf family has not been well elucidated.
      We have identified 11 additional zebrafish fgfs by conducting a homology-based
      search in the zebrafish genome and cDNA databases. The zebrafish fgf family now
      comprises at least 27 members. By conducting phylogenetic and gene location
      analyses, we examined relationships of zebrafish fgf genes with human FGF genes.
      All the zebrafish orthologs of human FGFs except for FGF9 have been identified.
      Zebrafish fgf9 might have been lost from the genome during evolution. In
      addition, six paralogs of zebrafish fgf genes have been identified. The
      phylogenetic analysis suggests that the zebrafish fgf gene family can be divided
      into seven subfamilies. The zebrafish fgf subfamilies are essentially consistent
      with the human FGF subfamilies, although some include potential paralogs. As the
      zebrafish system has proved useful for studying gene functions and genetic
      diseases, the present findings will be useful for elucidation of roles of FGFs in
      zebrafish and humans.

PMID- 18041923
TI  - Differential regulation of primitive myelopoiesis in the zebrafish by Spi-1/Pu.1
      and C/ebp1.
AB  - The zebrafish has become a powerful tool for analysis of vertebrate
      hematopoiesis. Zebrafish, unlike mammals, have a robust primitive myeloid pathway
      that generates both granulocytes and macrophages. It is not clear how this unique
      primitive myeloid pathway relates to mammalian definitive hematopoiesis. In this
      study, we show that the two myeloid subsets can be distinguished using RNA in
      situ hybridization. Using a morpholino-antisense gene knockdown approach, we have
      characterized the hematopoietic defects resulting from knockdown of the myeloid
      transcription factor gene pu.1 and the unique zebrafish gene c/ebp1. Severe
      reduction of pu.1 resulted in complete loss of primitive macrophage development,
      with effects on granulocyte development only with maximal knockdown. Reduction of
      c/ebp1 did not ablate initial macrophage or granulocyte development, but resulted
      in loss of expression of the secondary granule gene lys C. These data reveal
      strong functional conservation of pu.1 between zebrafish primitive myelopoiesis
      and mammalian definitive myelopoiesis. Further, these results are consistent with
      a conserved role between c/ebp1 and mammalian C/EBPE, whose ortholog in zebrafish
      has not been identified. These studies validate the examination of zebrafish
      primitive myeloid development as a model for human myelopoiesis, and form a
      framework for identification and analysis of myeloid mutants.

PMID- 18041927
TI  - Evolutionary and expression analysis of the zebrafish deubiquitylating enzyme,
      usp9.
AB  - Mouse Usp9x/Fam (fat facets in mouse) and its Drosophila ortholog faf (fat
      facets) encode substrate-specific deubiquitylating enzymes and are essential for
      early embryonic development. The zebrafish (Danio rerio) is a powerful tool for
      studying embryonic gene expression patterns and function, and to that end, we
      sought to characterize the zebrafish Usp9 ortholog. Zebrafish usp9 was identified
      from database searches, and the predicted Usp9 protein is very highly conserved
      in mouse (90% identical and 94% similar) over its entire length. Phylogenetic
      analysis indicated that vertebrate Usp9s are highly clustered and separate from
      the USP9Y and Drosophila forms. We examined the developmental expression of usp9
      from fertilization to 2 days postfertilization. usp9 is initially expressed
      ubiquitously but later restricted to the cephalic central nervous system, the
      developing lens, distal tips of the pectoral fin bud, and migrating endoderm. The
      extraordinary level of conservation between the mouse and zebrafish genes,
      coupled with equivalent expression patterns, makes zebrafish an appropriate
      complementary system for the study of usp9 in development.

PMID- 18041928
TI  - Molecular cytogenetics of blind mexican tetra and comments on the karyotypic
      characteristics of genus Astyanax (Teleostei, Characidae).
AB  - Astyanax mexicanus is popularly known as the blind Mexican tetra or blind cave
      tetra and has been extensively studied regarding various aspects of its biology
      and genetics. Despite the identification of linkage maps of genes related to
      quantitative trait loci by many recent studies, only its diploid number was known
      from a cytogenetical point of view. With the purpose of providing a base for
      comparative studies and for the elucidation of physical maps for the species,
      cytogenetical studies were performed in a group of 10 blind specimens from
      Mexico. All the individuals presented 2n = 50 chromosomes and a karyotypic
      formula composed of 8M + 18SM + 12ST + 12A. A few specimens presented one or two
      B microchromosomes of the acrocentric type. Although simple argyrophilic
      nucleolar organizer regions (Ag-NORs) were evidenced, fluorescence in situ
      hybridization (FISH) with an 18S rDNA probe evidenced eight sites, and six sites
      were observed with a 5S rDNA probe. Little constitutive heterochromatin was
      observed, mainly related with the Ag-NORs and located close to the centromeres,
      including those from the B microchromosomes. A few pericentromeric
      heterochromatin regions were mainly constituted by GC, including the one from the
      Ag-NOR. Very subtle markings were observed by FISH with an As-51 satellite DNA
      probe. The B microchromosome did not present ribosomal genes or satellite DNA.
      Chromosomal aspects of the genus Astyanax are discussed.

PMID- 18041929
TI  - A rapid apoptosis assay measuring relative acridine orange fluorescence in
      zebrafish embryos.
AB  - The ability to easily analyze apoptosis is important in studies of molecular cell
      biology and to evaluate the relative toxicity of different treatments or
      environments. This is particularly the case when substances such as morpholino
      oligonucleotides are injected into embryos, as such treatments can cause
      widespread, complex patterns of apoptosis. Zebrafish embryos are well suited for
      cell biological and environmental toxicity analyses, but the need remains for a
      simple method that can analyze levels of apoptosis in a statistically significant
      number of embryos. Here we present a "group fluorescence" method for rapid, large
      scale analysis of relative levels of apoptosis based on densitometric techniques.

PMID- 18041930
TI  - Low-cost aquatic lab animal holding system.
AB  - We have constructed a low-cost aquatic animal holding system that provides an
      alternative to expensive, commercially available systems. Our flow-through system
      is especially useful for programs that are limited in space and funding. The easy
      assembly and maintenance of the system are advantages for the researchers who may
      be unfamiliar with aquatic animals.

PMID- 18041935
TI  - Overview of Parkinson's disease.
AB  - This overview of Parkinson's disease is designed to serve as a background to the
      discussion elsewhere in this supplement on the pharmacotherapy used in its
      management. Parkinson's disease is a common progressive neurodegenerative
      condition associated with significant disability and negative impact on quality
      of life. Although the cause of Parkinson's disease is unknown, the pathologic
      manifestation involves the loss or dysfunction of dopaminergic neurons in the
      substantia nigra pars compacta. Characteristic clinical manifestations include
      difficulty with coordinated movement such as asymmetric resting tremor, rigidity,
      and bradykinesia. These symptoms and their response to levodopa constitute the
      basis for a clinical diagnosis of Parkinson's disease. Postural instability and
      gait abnormalities occur in more advanced disease. Although there is no cure for
      Parkinson's disease, a number of pharmacologic treatments are available for
      managing the motor and nonmotor symptoms. Research is under way to assess the
      disease-modifying ability of both standard and newer treatments.

PMID- 18041936
TI  - Pharmacotherapy for Parkinson's disease.
AB  - The available pharmacotherapies for Parkinson's disease address symptomatology
      because no agent has been demonstrated to provide definite neuroprotection
      against the disease. Choice of pharmacotherapy must include consideration of
      short-term benefits as well as long-term consequences. Patients with mild
      Parkinson's disease often function adequately without symptomatic treatment.
      However, recent data suggest that initiation of treatment with a well-tolerated
      agent (e.g., the monoamine oxidase [MAO]-B inhibitor rasagiline) in the absence
      of functional impairment is associated with improved long-term outcomes.
      Consideration should also be given to many patient-specific factors, including
      patient expectations, level of disability, employment status, functional as well
      as chronologic age, expected efficacy and tolerability of drugs, and response to
      previous Parkinson's disease therapies. Increasingly, initial monotherapy begins
      with a nondopaminergic agent or, if the patient is considered functionally young,
      a dopamine agonist. Since Parkinson's disease is a progressive disorder,
      adjustments to pharmacotherapy must be expected over time. When greater
      symptomatic relief is desired, or in the more frail elderly patient, levodopa
      therapy should be considered. If motor fluctuations develop, addition of a
      catechol-O-methyltransferase inhibitor or MAO-B inhibitor should be considered.
      For management of levodopa-induced dyskinesias, addition of amantadine is an
      option. Surgery may be considered when patients need additional symptomatic
      control or are experiencing severe motor complications despite pharmacologically
      optimized therapy.

PMID- 18041937
TI  - Monoamine oxidase-B inhibition in the treatment of Parkinson's disease.
AB  - Inhibitors of monoamine oxidase (MAO) with selectivity and specificity for MAO
      type B prolong the activity of both endogenously and exogenously derived
      dopamine, making them an option either as monotherapy in early Parkinson's
      disease or as adjunctive therapy in patients treated with levodopa who are
      experiencing motor complications. In addition to symptomatic benefits,
      experimental data suggest that MAO-B inhibitors may be neuroprotective through
      MAO-B inhibition and other mechanisms that have yet to be clearly defined. The
      two available MAO-B inhibitors approved for use in the United States, rasagiline
      and selegiline, each provide symptomatic relief as monotherapy and as adjunctive
      therapy, and have shown potential disease-modifying effects in experimental
      models and clinical studies. Selegiline in a conventional tablet formulation is
      less bioavailable than rasagiline, resulting in limited potency. It also has
      amphetamine metabolites that may produce adverse effects and interfere with any
      putative disease-modifying effects. The oral disintegrating tablet formulation of
      selegiline allows pregastric absorption, minimizing first-pass metabolism,
      thereby increasing selegiline bioavailability and reducing the concentration of
      amphetamine metabolites. Rasagiline, more potent than selegiline, exhibits
      disease-modifying effects in experimental models and lacks amphetamine
      metabolites. Both the symptomatic and potential disease-modifying effects of
      rasagiline are under investigation. A third agent with MAO-B inhibition
      properties, safinamide, is in phase III development. Although not yet approved,
      safinamide may offer the added advantage of combined MAO-B and dopamine reuptake
      inhibition.

PMID- 18041938
TI  - Investigator profile: an interview with Danica Zivkovic, Ph.D.

PMID- 18041939
TI  - Fish models in toxicology.

PMID- 18041940
TI  - Zebrafish in the wild: a review of natural history and new notes from the field.
AB  - The zebrafish, Danio rerio, has emerged as a major model organism for biomedical
      research, yet little is known about its natural history. We review the literature
      pertaining to the geographic range, biotic and abiotic habitats, and life cycle
      of the zebrafish. We also report our own field study to document several aspects
      of zebrafish natural history across sites in northeast India. We found zebrafish
      particularly abundant in silt-bottomed, well-vegetated pools and rice paddies
      adjacent to slow moving streams at a range of elevations. We further identified
      co-occurring fishes likely to be zebrafish competitors and predators. Finally, we
      present observations that indicate substantial habitat degradation and loss, and
      suggest guidelines for documenting and preserving natural zebrafish populations.

PMID- 18041941
TI  - Construction of bacterial artificial chromosome libraries for the Lake Malawi
      cichlid (Metriaclima zebra), and the blind cavefish (Astyanax mexicanus).
AB  - Teleost fishes have become important models for studying the evolution of the
      genetic mechanisms of development. A key resource for comparative genomics and
      positional cloning are large-insert libraries constructed in bacterial artificial
      chromosomes. We have constructed bacterial artificial chromosome libraries for
      two species of teleost fish that are important models for the study of
      developmental evolution. Metriaclima zebra is one of several hundred closely
      related, morphologically diverse, haplochromine cichlids which have evolved over
      the last one million years in Lake Malawi, East Africa. The Mexican tetra,
      Astyanax mexicanus, is well known for adaptations related to the recent evolution
      of blind cave-dwelling forms. Clones and high-density filters for each library
      are available to the scientific community through the Hubbard Center for Genome
      Studies.

PMID- 18041942
TI  - Embryonic expression and steroid regulation of brain aromatase cyp19a1b in
      zebrafish (Danio rerio).
AB  - Estradiol is produced from testosterone by the aromatase gene, cyp19. In the
      zebrafish Danio rerio, brain aromatase, cyp19a1b, is highly expressed during
      development. We report the developmental expression pattern of cyp19a1b using
      whole mount in situ hybridization and describe hormonal effects on the gene using
      RT-PCR. Expression is up-regulated between 24 and 48 hours postfertilization
      (hpf). Localized expression of cyp19a1b is first detected at 48 hpf in the
      preoptic area, hypothalamus, terminal nerve, and olfactory bulb. The gene is
      itself induced by estradiol in a positive feedback loop. Testosterone exposure
      also induces the cyp19a1b gene in zebrafish; however, a majority of this
      induction is blocked by an estrogen receptor antagonist. The expression pattern
      of aromatase in the brain and its control by steroid hormones is well conserved
      among the vertebrate lineage.

PMID- 18041943
TI  - Effects of nicotine on growth and development in larval zebrafish.
AB  - In this study, larval zebrafish (Danio rerio) were chronically exposed to
      nicotine concentrations of 5, 10, or 20 mg/L (corresponding to 10, 20, or 40
      microM) beginning at 1 day postfertilization. Larval growth, morphology, and
      behavior were examined at day 10. Results indicate that nicotine exposure
      significantly reduces notochord length and eye diameter (growth), adversely
      affects the startle responses (behavior), and decreases survival. These findings
      parallel results on the deleterious effects of nicotine on development in other
      animals and indicate that zebrafish may be a good model to further study factors
      affecting vertebrate development.

PMID- 18041944
TI  - Diet affects spawning in zebrafish.
AB  - Seven-month-old zebrafish (Danio rerio) were fed four different diets to test the
      hypothesis that diet affects spawning success and resulting characteristics of
      eggs and offspring. The diets were: the recommended feeding regime for zebrafish
      (a mixture of Artemia, flake feed, and liver paste); Artemia; a flake feed; and a
      commercially available trout diet. The number of eggs laid and average egg
      diameter were significantly different as functions of male, female, and
      individual matings. Fish fed the flake diet produced significantly fewer eggs
      (mean, 116) than fish fed all other diets (means, 166-187). However, the percent
      hatch of eggs from fish fed the flake diet (62.5%) was significantly higher than
      from fish fed the trout diet (19.5%). The percentages of hatched eggs from fish
      fed the control diet (36.2%) or Artemia (35.6%) were not significantly different
      from each other or from fish fed the other two diets. Wet weight and diameter of
      eggs were not significantly affected by diet. Larval length was significantly
      higher from parents fed the flake diet (14.5 mm) compared to larvae from parents
      fed Artemia (13.7 mm). Length of larvae from fish fed the control or trout diets
      was intermediate and not significantly different from fish fed the flake diet or
      Artemia. Larval weight was not significantly affected by dietary treatment, but
      offspring from fish fed the flake diet were heavier than larvae from adults fed
      any of the other diets. Feeding adult zebrafish the flake diet alone resulted in
      more viable offspring and larger larvae and is a simpler feeding regime than the
      current recommendation. The authors recommend feeding adult zebrafish flake diets
      to satiation three times daily for maximum production of viable offspring.

PMID- 18041948
TI  - Foodborne disease trends and reports.

PMID- 18041949
TI  - A role for translational control in listerial osmoregulation and strain
      variation?

PMID- 18041950
TI  - The use of bulk tank milk samples to monitor trends in antimicrobial resistance
      on dairy farms.
AB  - The routine monitoring of bacteria obtained from bulk tank milk (BTM) may be an
      important tool for detecting farm-level trends in antimicrobial resistance on
      dairy farms. This study describes and compares antimicrobial susceptibility
      patterns of Salmonella enterica subspecies enterica (Salmonella) and Escherichia
      coli recovered from dairy BTM. BTM from more than 400 dairies in a dairy-intense
      region of California were sampled eight times at 2- to 3-month intervals over a
      29-month period. From Salmonella positive and Salmonella negative herds any one
      Salmonella and three E. coli isolates per sample were tested for susceptibility
      to 12 antimicrobials. The prevalence of multiple drug resistant (MDR) E. coli was
      assessed in relation to Salmonella on the farm, farm size, season, MDR
      Salmonella, and serovar. At each sampling period, 10-21% and 54-77% of the dairy
      farms were positive for Salmonella and E. coli, respectively. The most commonly
      recovered Salmonella serovars were Montevideo (33%), Typhimurium (14%), Dublin
      (13%), and Give (11%). Two-thirds, respectively, of 478 Salmonella and 1577 E.
      coli isolates were pan-susceptible. The antimicrobial resistance patterns of MDR
      Salmonella tended to be serovar dependent and were different from the
      antimicrobial resistance patterns of MDR E. coli. MDR E. coli were more likely to
      be recovered from dairies with MDR Salmonella. There were no associations between
      MDR E. coli and season, Salmonella serovar detected in the BTM, or dairy herd
      size. Bulk milk E. coli and Salmonella could be valuable to monitor the dynamics
      of antimicrobial resistance in dairy milk production.

PMID- 18041951
TI  - Phenotypic and molecular characterization of Listeria monocytogenes strains
      isolated from a marine environment in Morocco.
AB  - Microbiological analysis of 1025 marine samples, including 345 from seawater, 337
      from shellfish, and 343 from sediments collected between January 2000 and
      December 2002 from 18 shellfish sites on the Atlantic coast of mid-west of
      Morocco (Agadir region), yielded 143 strains of Listeria (Listeria monocytogenes:
      38; L. innocua: 109; L. ivanovii: 1). The overall incidence of Listeria sp. in
      the coastal environment was 5.3%. Thirteen L. monocytogenes strains were isolated
      from seawater, 7 from sediment, and 12 from shellfish. The 38 strains of L.
      monocytogenes were phenotypically characterized. All belonged to two chemotypes
      according to appareillage et procede d'identification (API) Listeria
      classification: 8 strains were type 2510, alpha-mannosidase-negative and
      hemolytic; and 30 strains were type 6510, alpha-mannosidase-positive, of which 8
      strains were nonhemolytic. All the L. monocytogenes strains belonged to the 1/2
      serogroup, with serovar 1/2b clearly prevalent (78.9%), although some
      nonhemolytic strains were serovar 1/2a. This collection of L. monocytogenes
      strains included 6 different pulsotypes as assessed by DNA macrorestriction with
      the restriction enzymes AscI and ApaI.

PMID- 18041952
TI  - Retail meat consumption and the acquisition of antimicrobial resistant
      Escherichia coli causing urinary tract infections: a case-control study.
AB  - BACKGROUND: The increasing incidence of community-acquired urinary tract
      infections (UTIs) caused by antimicrobial resistant Escherichia coli, and
      observations of potential outbreaks of UTI-causing E. coli, suggest that food may
      be an important source of E. coli in women who develop UTI. We sought to
      determine if acquisition of and infection with a UTI-causing, antimicrobial
      resistant E. coli isolate is associated with a woman's dietary habits,
      specifically her preparation and consumption of retail meat products. METHODS:
      Between April 2003 and June 2004, a case-control study was conducted. The dietary
      habits of women with UTI caused by an antimicrobial resistant E. coli (cases) and
      women with UTI caused by fully susceptible E. coli (controls) were compared.
      Broth microdilution was used to perform antimicrobial resistance testing. All E.
      coli isolates were genotyped by the pulsed-field gel electrophoresis (PFGE)
      method. RESULTS: Ninety-nine women met study criteria. Women who were infected
      with multidrug-resistant E. coli reported more frequent chicken consumption
      (adjusted OR = 3.7, 95% CI 1.1, 12.4). Women with UTI caused by an ampicillin- or
      cephalosporin-resistant E. coli isolate reported more frequent consumption of
      pork (adjusted OR = 3.2, 95% CI 1.0, 10.3 and adjusted OR = 4.0, 95% CI 1.0,
      15.5, respectively). Frequent alcohol consumption was associated with
      antimicrobial resistant UTI. CONCLUSIONS: This study provides epidemiologic
      evidence that antimicrobial resistant, UTI-causing E. coli could have a food
      reservoir, possibly in poultry or pork.

PMID- 18041953
TI  - Assessment of the prevalence of Mycobacterium avium subsp. paratuberculosis in
      commercially pasteurized milk.
AB  - Conflicting laboratory-acquired data have been published about the heat
      resistance of Mycobacterium avium subsp. paratuberculosis (MAP), the cause of the
      deadly paratuberculosis (Johne's disease) of ruminants. Results of surveys of the
      presence of MAP in industrially pasteurized milk from several countries are
      conflicting also. This paper critically reviews the available data on the heat
      resistance of MAP and, based on these studies, a quantitative model describing
      the probability of finding MAP in pasteurized milk under the conditions
      prevailing in industrialized countries was derived using Monte Carlo simulation.
      The simulation assesses the probability of detecting MAP in 50-mL samples of
      pasteurized milk as lower than 1%. Hypotheses are presented to explain why higher
      frequencies were found by some authors; these included improper pasteurization
      and cross-contamination in the analytical laboratory. Hypotheses implicating a
      high rate of inter- and intraherd prevalence of paratuberculosis or heavy
      contamination of raw milk by feces were rejected.

PMID- 18041954
TI  - Longitudinal study of a clonal, subclinical outbreak of Salmonella enterica
      subsp. enterica serovar Cerro in a U.S. dairy herd.
AB  - Salmonellae are a major group of foodborne pathogens known to affect both humans
      and animals. Dairy cattle are a known reservoir of these bacteria and human
      Salmonella infections have been associated with the consumption of improperly
      processed or contaminated dairy products. Many of the over 2500 known serotypes
      of Salmonella are known to infect cattle, resulting in asymptomatic to fatal
      salmonellosis. This study describes the course of a Salmonella outbreak and
      subsequent endemic infection on a dairy farm in Pennsylvania. The outbreak was
      initially detected when a few cows with clinical symptoms and one fatality were
      found to be infected with Salmonella enterica subsp. enterica serovar Typhimurium
      var. Copenhagan. Based upon sampling of the farm environment, Salmonella
      Typhimurium var. Copenhagan was succeeded within 3 months by Salmonella enterica
      subsp. enterica serovar Kentucky. Salmonella enterica subsp. enterica serovar
      Cerro ultimately supplanted Typhimurium var. Copenhagan and Kentucky in
      individual animals and environmental samples and persisted in the herd at high
      prevalence for almost 2 years. Since there were no obvious clinical consequences
      of the Salmonella Cerro infection, these data suggest that some serotypes of S.
      enterica subsp. enterica can behave as commensal organisms in dairy cattle and
      illustrate the difficulties of controlling Salmonella in milk production systems.
      The consistent finding of Salmonella in the environment reinforces the potential
      for human exposure to this pathogen and the need to understand the dynamics and
      ecology of Salmonella in dairy production settings.

PMID- 18041955
TI  - Proteomic analysis to identify the role of LuxS/AI-2 mediated protein expression
      in Escherichia coli O157:H7.
AB  - Microorganisms employ autoinducer molecules to modulate various bacterial
      processes including virulence expression, biofilm development, and
      bioluminescence. The universal autoinducer molecule AI-2 is hypothesized to
      mediate cell signaling in Escherichia coli O157:H7. We investigated the role of
      AI-2 on the E. coli O157:H7 cellular proteins using a two-dimensional (2D) gel
      electrophoresis-based proteomic approach. The protein expression patterns between
      two experimental comparisons were studied namely, 1) a wild type E. coli O157:H7
      and its isogenic luxS mutant, and 2) the luxS mutant and the luxS mutant
      supplemented with AI-2 molecules. Eleven proteins were differentially expressed
      between the wild type and the luxS mutant strain, whereas 18 proteins were
      differentially expressed in the luxS mutant strain when supplemented with AI-2.
      The tryptophan repressor binding protein (WrbA), phosphoglycerate mutase (GpmA),
      and a putative protein YbbN were found to be differentially expressed under both
      experimental comparisons. The FliC protein which is involved in flagellar
      synthesis and motility was up-regulated in the wild type strain but was not
      influenced by the addition of synthetic AI-2 molecules to the luxS mutant
      suggesting the involvement of signaling molecules other than AI-2 on flagellar
      synthesis and motility.

PMID- 18041956
TI  - Discriminating between strains of Escherichia coli using pulsed-field gel
      electrophoresis and BOX-PCR.
AB  - In this study, we evaluated two biomolecular techniques for discriminating
      between strains of Escherichia coli isolated form a variety of sources. The DNA
      of 211 strains of E. coli collected from dairy farms, calves, feces, pigs,
      primates, humans, and food products was analyzed by pulsed-field gel
      electrophoresis (PFGE) and repetitive-element polymerase chain reaction using the
      BOXA1 primer (BOX-PCR). Objectives of the present study were to compare PFGE and
      BOX-PCR for discriminating among strains of E. coli and investigate their
      capability in clustering E. coli strains according to the origin of bacterial
      isolation. Our results showed that PFGE and BOX-PCR were both able to distinguish
      closely related strains of E. coli; however, PFGE was able to discriminate
      between isolates indistinguishable by BOX-PCR and interpretation of PFGE data was
      easier. BOX-PCR proved to have good discrimination power, was less expensive, and
      could be performed in a PCR thermocycler. Neither of the methods used were
      effective in clustering E. coli strains according to the source of the organism.

PMID- 18041957
TI  - Antibacterial activity of guava (Psidium guajava L.) and Neem (Azadirachta indica
      A. Juss.) extracts against foodborne pathogens and spoilage bacteria.
AB  - The antibacterial activity of guava (Psidium guajava) and neem (Azadirachta
      indica) extracts against 21 strains of foodborne pathogens were determined-
      Listeria monocytogenes (five strains), Staphylococcus aureus (four strains),
      Escherichia coli O157:H7 (six strains), Salmonella Enteritidis (four strains),
      Vibrio parahaemolyticus, and Bacillus cereus, and five food spoilage bacteria:
      Pseudomonas aeroginosa, P. putida, Alcaligenes faecalis, and Aeromonas hydrophila
      (two strains). Guava and neem extracts showed higher antimicrobial activity
      against Gram-positive bacteria compared to Gram-negative bacteria except for V.
      parahaemolyticus, P. aeroginosa, and A. hydrophila. None of the extracts showed
      antimicrobial activity against E. coli O157:H7 and Salmonella Enteritidis. The
      minimum inhibitory concentration (MIC) of ethanol extracts of guava showed the
      highest inhibition for L. monocytogenes JCM 7676 (0.1 mg/mL), S. aureus JCM 2151
      (0.1 mg/mL), S. aureus JCM 2179 (0.1 mg/mL), and V. parahaemolyticus IFO 12711
      (0.1 mg/mL) and the lowest inhibition for Alcaligenes faecalis IFO 12669,
      Aeromonas hydrophila NFRI 8282 (4.0 mg/mL), and A. hydrophila NFRI 8283 (4.0
      mg/mL). The MIC of chloroform extracts of neem showed similar inhibition for L.
      monocytogenes ATCC 43256 (4.0 mg/mL) and L. monocytogenes ATCC 49594 (5.0 mg/mL).
      However, ethanol extracts of neem showed higher inhibition for S. aureus JCM 2151
      (4.5 mg/mL) and S. aureus IFO 13276 (4.5 mg/mL) and the lower inhibition for
      other microorganisms (6.5 mg/mL). No significant effects of temperature and pH
      were found on guava and neem extracts against cocktails of L. monocytogenes and
      S. aureus. The results of the present study suggest that guava and neem extracts
      possess compounds containing antibacterial properties that can potentially be
      useful to control foodborne pathogens and spoilage organisms.

PMID- 18041959
TI  - Salmonella contamination of turkey from processing to final product--a process to
      product perspective.
AB  - Food safety and the development of an understanding of issues surrounding
      pathogens associated with food is of considerable importance in modern-day food
      production. The design and use of risk models to estimate the likelihood of human
      illness has become an important part of our understanding of food safety issues.
      In order to quantify food safety risks, the first requirement is to estimate the
      occurrence of the pathogen associated with a particular production system. As
      such, an assessment of whether interventions significantly reduce these risks can
      be made. In light of recent events in food production including pathogens in
      ready to eat foods and outbreaks of Escherichia coli O157:H7 associated with
      produce, the development and implementation of risk models will continue to gain
      importance in the coming years. This paper focuses on some of the current
      research ongoing at North Dakota State University to develop a greater
      understanding of Salmonella as it pertains to turkey production and processing in
      the Midwest. This overview of studies of Salmonella in turkey production stems
      from a presentation of research made at the Integrated Risk Studies: Gate to
      Plate-Current Issues and Future Strategies Conference held in Fargo, ND, May 4-5,
      2006.

PMID- 18041960
TI  - Voluntary vs. mandatory approaches to food safety: considering heterogeneous
      firms.
AB  - A critical assessment of voluntary approaches in regulatory programs is
      presented. When accounting for heterogeneous firms, with varying effectiveness of
      risk control, the optimality of a lump-sum financial incentive to encourage
      voluntary adoption is questioned. The paper uses a game-theoretic model to
      characterize the strategies of a regulator and firms. Using robust comparative
      statics, it can be shown that less efficient firms are less likely to participate
      in a voluntary food safety program. Adverse selection leads to lower overall risk
      control, suggesting mandatory control may be preferred.

PMID- 18041961
TI  - Occurrence of antimicrobial-resistant salmonella species in raw and ready to eat
      turkey meat products from retail outlets in the midwestern United States.
AB  - OBJECTIVES: To investigate occurrence of Salmonella in raw and ready to eat (RTE)
      turkey from retail outlets, determine factors associated with its occurrence and
      antimicrobial-resistance patterns. MATERIALS AND METHODS: A total of 959 turkey
      products (raw, n = 345; and RTE, n = 614) were purchased in 3 months from four
      stores in one city in the midwestern United States. Chi-square and logistic
      regression analyses were used to test for associations of microbial contamination
      with product type and brand, expiration date, sampling time, and retail store.
      Antimicrobial resistance of Salmonellae was determined using a National
      Antimicrobial Resistance Monitoring System (NARMS) panel of antimicrobials.
      RESULTS: Overall, 2.2% (21/959) of the samples (4.1% [14/345] raw and 1.1%
      [7/614] RTE) were contaminated with Salmonella. A significant difference in
      Salmonella occurrence (p < 0.05), between meat type (raw vs. RTE; OR = 4.2, 95%
      CI = 1.6, 10.8); and sampling month (p < 0.05) was reported, but not between
      retail stores and product brands. Salmonellae belonged to 6 serotypes: Hadar,
      Heidelberg, Typhimurium var. Copenhagen, Newport, Saintpaul, and Agona.
      Salmonellae from raw turkey exhibited higher antimicrobial resistance (53%)
      compared to those from RTE products (33%). Multidrug resistance was exhibited by
      62% of Salmonellae (86% RTE, 50% raw meats). CONCLUSION AND CLINICAL
      APPLICATIONS: Turkey (both raw and RTE) may occasionally be contaminated with
      antimicrobial-resistant Salmonellae whose occurrence was influenced by sampling
      month and meat type. Continued surveillance of Salmonella occurrence in meat
      products, in particular RTE ones, is warranted in order to ensure a safe food
      supply.

PMID- 18041962
TI  - How university researchers can contribute to farm-to-table risk assessments:
      Listeria monocytogenes as an example.
AB  - As a part of the Sanitary and Phytosanitary (SPS) agreement, the World Trade
      Organization requires that member countries establish SPS measures on the basis
      of an appropriate risk assessment. In addition, many governments use risk
      assessment in their management of food safety. Consequently, a number of risk
      assessments for different foodborne pathogens have been conducted. Risk
      assessments have also been successfully used as a research tool. While,
      historically, risk assessments are typically initiated by government agencies,
      university-based researchers are increasingly becoming involved in risk
      assessments. The purpose of this article is to illustrate the role that
      university researchers can play in the development and refinement of food safety
      risk assessments, including possible roles in (1) de novo development or
      refinement of risk assessment (including farm-to-table risk assessment), (2) data
      collection supporting risk assessments, and (3) development of new methodological
      techniques. Transmission of the foodborne pathogen Listeria monocytogenes through
      the food production chain and risk assessments addressing transmission of this
      pathogen are used as an example to highlight the roles of university researchers
      in food safety risk assessments.

PMID- 18041963
TI  - Efficacy of vaccination to reduce Salmonella prevalence in live and slaughtered
      swine: a systematic review of literature from 1979 to 2007.
AB  - A systematic review was conducted to evaluate the efficacy of vaccination to
      reduce Salmonella prevalence in market weight finisher swine. A search of online
      databases and selected conference proceedings was conducted to identify relevant
      studies. The review process followed relevance screening, methodological quality
      assessment, and data extraction. Although multiple outcomes were frequently
      reported, only outcomes describing culture of Salmonella were extracted. Five
      clinical trials and 23 challenge studies were considered likely relevant to the
      review as they described vaccination to reduce Salmonella in swine. Five clinical
      trials reported vaccination was associated with reduced isolation of Salmonella
      in market weight pigs, however, information required to assess the internal
      validity of the study was often not described in the manuscripts. All challenge
      studies assessed vaccine efficacy in pigs aged <15 weeks reducing the relevance
      of results to the review which focused on market weight pigs. Only five of the 23
      challenge studies reported the majority of information necessary to evaluate the
      quality of vaccine studies. Given large variability in population type, sample
      size, type of vaccine, dose and dosing regimens, and type of outcomes observed,
      pooled data analysis was not possible, and therefore, a qualitative synthesis of
      the studies was conducted. Available evidence suggests that vaccination is
      associated with reduced Salmonella prevalence in swine at or near harvest;
      however, this conclusion is based on studies with design and reporting
      deficiencies that could potentially indicate biases with the outcome.

PMID- 18041964
TI  - Evaluation of Salmonella occurrence in domestic animals and humans in North
      Dakota (2000-2005).
AB  - OBJECTIVES: To evaluate the occurrence, serotypes, and antimicrobial
      susceptibility of Salmonellae from domestic animals and humans in North Dakota.
      MATERIALS AND METHODS: Salmonellosis data (2000-2005) in humans (n = 286) and
      animals (n = 258) were extracted from the North Dakota Department of Health
      (NDDoH) and North Dakota State University Veterinary Diagnostic Laboratory (NDSU
      VDL), and analyzed for temporal and spatial trends, and for other associations.
      Additionally, random samples of 35, 30, and 15 Salmonella isolates from NDSU-VDL,
      NDDoH, and North Dakota healthy cattle, respectively, were tested for
      antimicrobial susceptibility. RESULTS: Most animal salmonellosis occurred in
      cattle (64.7%) sheep (12%), pigs (10.9%), and bison (0.4%) with Salmonella
      Typhimurium (45.7%) as the predominant serotype; Salmonella Arizona (10.9%) and
      Dublin (10.5%) were host specific in sheep and cattle respectively. In humans,
      Salmonella Typhimurium (32.5%) and Salmonella Newport (11.2%) were predominant.
      Season influenced human (p = 0.027) and animal (p = 0.014) salmonellosis with
      cases peaking in the spring and summer for animals and humans, respectively.
      Salmonella Typhimurium case reports in humans were not seasonally related to
      domestic animals (p = 0.001) nor cattle (p = 0.001). Over time, case reports
      increased in humans but decreased in domestic animals. Most serotypes from
      domestic animals were multidrug resistant compared to human isolates. CONCLUSIONS
      AND APPLICATIONS: Many Salmonella serotypes (17) were involved in North Dakota
      human and animal salmonellosis with case reports closely related in fall and
      winter, but not during warmer months. Spatial clustering of human and animal
      cases was similar. Antimicrobial resistance was widespread but lower in human
      isolates. These data are helpful in determining future policy, research, and
      control strategies for salmonellosis in humans and domestic animals.

PMID- 18041966
TI  - Issues in older person nursing.

PMID- 18041967
TI  - Towards innovation: the development of a person-centred model of care for older
      people in acute care.
AB  - That the population is ageing poses many challenges for health care planners.
      Some argue that these challenges, exacerbated by limited funding, maintaining
      increased community expectations and the need for quality health care outcomes,
      may be overcome by exploring alternate models of care. These ideas have led
      health planners to reconceptualise contemporary philosophies of care with the
      current emphasis on multidisciplinary teams and a person-centred approach to
      care. This paper presents a model for the care of older people in the acute care
      setting. The concepts for the development of the model were derived from the
      international literature. In the model the care of older people is underpinned by
      a philosophy of person-centredness. The complex nature of care is represented
      along with those factors that enable a person-centred approach to be taken. The
      functions of the model in practice are highlighted and discussion of how it is
      being implemented within the acute care sector outlined.

PMID- 18041968
TI  - Trends and challenges in the management of tracheostomy in older people: the need
      for a multidisciplinary team approach.
AB  - The trend towards increasing representation of older people as recipients of
      health care in acute care settings is matched with a corresponding increase in
      the numbers of older people undergoing tracheostomy.The reasons for tracheostomy
      in this age group are varied, including respiratory failure, neurological
      injury/event and carcinomas. Further, current research supports early
      tracheostomy for patients requiring medium to long-term ventilation and
      unconscious patients at risk of airway obstruction. In spite of this increase
      very little has been written about decision making and ongoing nursing care for
      these patients. There is an abundance of literature on the physiological
      processes of aging and the problems related to comorbidities; however, there has
      been very little exploration of how these impact on the occurrence of
      complications and other outcomes for older patients with a tracheostomy, and the
      consequent implications for care provision. This article examines clinical issues
      of significance to older people with tracheostomy and outlines the implementation
      and benefits of a multidisciplinary team approach.

PMID- 18041969
TI  - Advance care planning (ACP): the nurse as 'broker' in residential aged care
      facilities.
AB  - This paper describes one aspect of a study that investigated how Advance Care
      Planning (ACP) was implemented in residential care facilities (RACFs) in
      Australia and the role of a Clinical Nurse Consultant (CNC) for ACP. Three RACFs
      were included in the study. This paper focuses on the implementation process of
      ACP by the CNC in the RACFs. The preliminary findings highlight the need to
      dispel the myths about ACP and Advanced Care Directives (ACDs), and how the CNC
      acted as a broker for ACP. The CNC's role is represented by a Nursing Brokerage
      Model. By revealing how ACP is implemented the research contributes to the
      limited existing knowledge of options that are currently available to older
      adults and their families in order to help them make care choices about the end
      of their lives.

PMID- 18041970
TI  - Person-centered approach to care (PCA): a philosophy of care and management for
      carers.

PMID- 18041971
TI  - Urinary stress incontinence and overactive bladder symptoms in older women.
AB  - Urinary incontinence - the accidental leaking of urine - is a major problem in
      Australia and has a significant impact on quality of life, affecting the social,
      psychological, physical and financial aspects of living. The prevalence of
      urinary incontinence is significantly higher in women than in men. While urine
      loss itself is a devastating symptom, older women are also likely to suffer lower
      urinary tract symptoms associated with the overactive bladder syndrome such as
      urgency, frequency, mixed incontinence and nocturia which are reported more
      frequently in older women. These symptoms disrupt activities of daily living as
      well as seriously disturbing sleep and general health status. Conservative nurse
      interventions have been shown to be effective in the management of these
      symptoms. Simple assessment tools suitable for use by primary level clinicians
      and conservative management strategies are discussed within the paper.

PMID- 18041972
TI  - The immediate needs of relatives during the hospitalisation of acutely ill older
      relatives.
AB  - The main aim of this study was to explore the immediate needs of the relatives of
      acutely ill older people during hospitalisation. The research question posed was:
      'What are the immediate needs of the relatives1 of acutely ill older people in
      the hospital setting?' A descriptive qualitative approach was utilized, with
      ethnographic data collection methods and thematic data analysis. Unstructured
      interviews were conducted with relatives of older people who were admitted for
      acute care. The setting for the study included two large tertiary referral
      hospitals located in two area health services in New SouthWales,Australia.
      Analysis of data revealed two themes: being informed and being there. Being
      informed describes the nature of the information that relatives need and why this
      is so important to them. Being there illustrates how relatives perceive their
      roles and responsibility during hospitalisation. It highlights the importance of
      this and the impact it has on individuals The findings highlight the importance
      of appreciating the family's experiences in relation to the care of their older
      family member. They point to the need for education of stakeholders to focus on
      relatives as well as the older patient, improved assessment incorporating a whole
      of family approach on admission to hospital, and finally, facilitating positive
      relationships between ward staff and families.

PMID- 18041973
TI  - The changing skill mix and scope of practice of health care workers in New South
      Wales: implications of education and training reforms for registered nurse
      practice, performance and education.

PMID- 18041974
TI  - The negative attitudes of nurses towards older patients in the acute hospital
      setting: a qualitative descriptive study.
AB  - AIM: This paper reports the findings of a sub-sample of interviews from a larger
      study designed to explore the attitudes of health care workers towards older
      people in that acute care setting. The discussion in this paper focuses only on
      interviews with nurses and their negative attitudes towards older people in their
      care. BACKGROUND: As Australia's ageing population continues to grow
      exponentially, their demand for hospital care also increases. Many nurses in the
      acute care setting have had little, if any, specialist education in the care of
      older people and therefore do not understand the extent of their needs. Coupled
      with the lack of specialist knowledge is the low status of older person care in
      this setting. Many nurses prefer to care for younger patients with acute
      illnesses that are curable (Nay 1993 in Nay & Garratt 2004: 61). As with the
      population at large, health care professionals hold negative views about old age
      and this is reflected in their attitudes. METHOD: The findings presented in this
      paper focus on data analysed from in depth interviews with nurses. As a prompt to
      discussions, nurses were presented with scenarios that exemplified both positive
      and negative attitudes to care. However, much of what was discussed in interviews
      focused on negative attitudes. Interviews with medical and allied health staff
      will be reported in a separate paper. RESULTS: The analysis of data with nurses
      reveals two themes and subthemes. 'Marginalisation and oppression of the older
      person' shows the ways in which nurses perceive older people are relegated to a
      lower status in the acute care setting, how this is 'contagious' and how 'lack of
      time' for care for older people is problematic and has become their
      'catchcry'.'Stereotyping the older person' depicts some of the ways in which this
      evolves, for example, through 'Chinese Whispers' (UsingEnglish.com 2006), but has
      become part of the ageist culture.

PMID- 18041975
TI  - Delirium dichotomy: a review of recent literature.
AB  - Delirium remains a commonly occurring problem for older people and staff in acute
      care settings. The aim of this review of current literature is to find
      contemporary evidence on which to base practice modalities. Although the
      literature provides an exposition of the concerns with which practitioners are
      currently faced and highlights the consistent themes identified, there is little
      research evidence regarding the effectiveness of treatment protocols for the
      management of older people with delirium in acute care setting.

PMID- 18041978
TI  - Nurses in general practice settings: roles and responsibilities.
AB  - Nurses are an important human resource, vital for the delivery of health services
      in countries across the globe. To improve the quality, access and affordability
      of primary care services to support rural and remote communities, in 2001, the
      Australian Government implemented the Nursing in General Practice Initiative
      [NIGPI] to increase the numbers of nurses to work in general practice settings.
      The NIGPI positions nurses as both a human resource and a human commodity. This
      paper examines how developments emerging from this initiative enable and
      constrain the role and responsibilities of nurses working in general practices in
      Australia.

PMID- 18041979
TI  - Where does practice nursing fit in primary health care?
AB  - Practice nursing is an integral and growing part of primary health care
      internationally and increasingly within the Australian health care system. The
      potential for practice nursing being considered as a specialty of community
      nursing, boundary issues in community nursing, and defining characteristics of
      practice nursing as a model of community-based nursing are discussed in this
      paper. As the author has worked as a practice nurse, personal reflections on the
      evolving practice nurse role are provided. Practice nursing is a dynamic entity
      and will continue to evolve in the primary health care setting. In order for
      practice nursing to meet the primary health care agenda, there is a need to
      incorporate a social model of health with the medical model of health and to
      promote research and scholarship to support this goal.

PMID- 18041980
TI  - Professional organisations and regulatory bodies: forging and advancing the role
      of nurses in Australian primary care.

PMID- 18041981
TI  - Leadership in primary health care: an international perspective.
AB  - A primary health care approach is essential to contemporary nursing roles such as
      practice nursing. This paper examines the evolution of primary health care as a
      global strategy for responding to the social determinants of health. Primary
      health care roles require knowledge of, and a focus on social determinants of
      health, particularly the societal factors that allow and perpetuate inequities
      and disadvantage. They also require a depth and breadth of leadership skills that
      are responsive to health needs, appropriate in the social and regulatory context,
      and visionary in balancing both workforce and client needs. The key to succeeding
      in working with communities and groups under a primary health care umbrella is to
      balance the big picture of comprehensive primary health care with operational
      strategies for selective primary health care. The other essential element
      involves using leadership skills to promote inclusiveness, empowerment and health
      literacy, and ultimately, better health.

PMID- 18041982
TI  - Divisions of general practice and practice nurse development in Australia.
AB  - Nurses are consistently being seen as an integral part of a team approach to
      primary care service delivery, with significant policy initiatives being directed
      towards their employment in Australian general practice. Furthermore they are
      being increasingly recognised to add a value to general practice that is more
      than simply the 'sum of its parts'.This recognition, for GPs and practices, has
      often occurred on the back of an experience that has been provided or illustrated
      by a Division of General Practice. Divisions as the face of 'organised general
      practice' in this country have been instrumental in providing a broad range of
      support strategies and development opportunities for practice nursing, especially
      over the last five to ten years. Essentially, the role of Divisions has been
      about increasing connectivity, and acting as 'brokers' of information,
      opportunities, and in some cases even resources. Divisions have made a
      significant contribution to achievements in practice nurse development, but this
      has not been without challenges. As the evolution of Australian practice nursing
      reaches a crucial stage, Divisions can play a pivotal role in advancing this
      development but must seek partnerships to be effective and should continue to
      broaden their scope.

PMID- 18041983
TI  - Multiprofessional working, interprofessional learning and primary care: a way
      forward?
AB  - Across all sectors of health and social care there is a growing need for
      collaboration between professionals, agencies, providers and above all with the
      people they seek to serve. The significant challenge is how to create, within the
      existing and future workforce, the capability to work in multi professional teams
      capable of effective collaboration. The intention of this paper is to explore the
      implications that multi- or more specifically inter-professional learning may
      have for collaboration within primary care. As part of this, the state of the
      current evidence base regarding this form of learning will be explored. However,
      just as this way of learning is but one element in a wider picture of health
      care, so the focus will also include the implications for a workforce relevant to
      future primary care.

PMID- 18041984
TI  - Policy development to support nursing in Australian general practice: an
      overview.
AB  - There has been a groundswell of change, which has increased the profile and
      diversity of the role for nurses working in general practice. The need for change
      has been driven by the requirement to deliver quality, safe health care services
      in an environment that is complex and increasingly under pressure. Australian
      government initiatives have played an important part in shaping the role for the
      general practice nurse and supporting a team based approach to care in general
      practice. Professional groups have also played a key role in advocating for
      change and supporting new initiatives to enhance and promote community health and
      wellbeing.

PMID- 18041985
TI  - Investing in primary care nursing: an important strategy in improving the health
      and well-being of women.

PMID- 18041986
TI  - Expanding roles of Aboriginal health workers in the primary care setting: seeking
      recognition.
AB  - The work of Aboriginal health workers (AHWs) in the primary care setting is
      discussed, emphasising that partnership with non-Indigenous health providers such
      as nurses and general practitioners brings complementary skills together to
      improve the health care available to Aboriginal clients, and to decrease the
      cultural and communication barriers to delivering such health care. The diverse
      skills and responsibilities of AHWs, which include clinical, health promotion,
      education and leadership roles, are illustrated. The current focus on increasing
      AHW educational opportunities, and the need to recognise AHWs as core health
      professionals and equal members of the health care team is presented. The
      increasing recognition of the role of AHWs in providing cultural mentorship for
      non-Indigenous colleagues is discussed.

PMID- 18041987
TI  - Practice nursing in rural Australia.
AB  - Rural Australia faces unique issues in workforce management and health care
      delivery. This paper provides an integrated review of the existing literature
      describing the work of practice nurses in rural Australia and the perceptions of
      consumers. Distinct differences are evident in the role of the practice nurse
      between rural and metropolitan practices. A key difference is that the rural
      practice nurse is known within the community and plays an important role in care
      coordination. Findings from two studies of consumer perceptions of the role of PN
      in rural areas suggest that the more remotely located the consumer, the greater
      is their perception that the nurse works under the direct supervision of the
      doctor. Currently, remotely located residents do not support an expanded
      autonomous role for the nurse. Greater research is required to develop the role
      of the practice nurse in rural Australia.

PMID- 18041988
TI  - Nurses in primary care and the nurse practitioner role in Thailand.
AB  - Thailand supports a system of universal health care coverage and promotes a
      system of primary care. Effective and efficient primary health care can improve
      health through increasing access and thereby reducing inequities. Nurses are key
      providers of primary care services, particularly in remote areas and play an
      important role in improving the health and well-being of the Thai community.

PMID- 18041989
TI  - Meeting a primary care challenge in the United States: chronic illness care.
AB  - Leading health care experts in the United States have stated that the greatest
      primary care challenge today is meeting the complex needs of patients with
      chronic illness/long-term conditions or impairment.To address this challenge,
      there is a need for health care system redesign that requires a multidisciplinary
      team approach, including active participation from professional nurses. In
      particular, it is essential for advanced practice nurses to provide leadership in
      health systems design for which they are specifically trained and experienced. In
      this article, the primary care challenge related to chronic illness care
      management is addressed. Future implications for community-based, chronic illness
      care delivery and the education of future health care providers with a focus on
      advanced practice nurses will also be discussed.

PMID- 18041990
TI  - Primary health care nurse practitioners in Canada.
AB  - Canada, like many countries, is in the midst of primary health care reform. A key
      priority is to improve access to primary health care, especially in remote
      communities and areas with physician shortages. As a result, there is an
      increased emphasis on the integration of primary health care nurse practitioners.
      As of March 2006, legislation exists in all provinces and two territories in
      Canada that allows nurse practitioners (NPs) to implement their expanded nursing
      role. In this paper, we will briefly review the historical development of the NP
      role in Canada and situate it in the international context; describe the NP role,
      supply of NPs in the country, and the settings in which they work; propose an NP
      practice model framework; summarize facilitators and barriers to NP role
      implementation in primary health care delivery; and outline strategies to address
      the barriers.

PMID- 18041991
TI  - Research and development: reflections of practice nurse research fellows.

PMID- 18041992
TI  - The research potential of practice nurses: what contribution to primary health
      care research?
AB  - Primary health care (PHC) is at the core of effective, sustainable population
      healthcare. Although PHC research has been described as the missing link in the
      development of high-quality, evidence-based health care for populations, research
      outputs have been disappointingly low in Australia and overseas. This paper
      reviews the current status of PHC research in Australia, particularly relating to
      funding and research capacity building needed to conduct high quality and
      relevant research with significant transfer potential for practice and policy. It
      explores the likely contribution of research-trained practice nurses (R-T PNs) as
      study coordinators, rather than as independent nurse researchers, although this
      is certainly possible, and proposes adapting a successful secondary care research
      model for use in the PHC research setting.

PMID- 18041993
TI  - Strategic directions for developing the Australian general practice nurse role in
      cardiovascular disease management.
AB  - Practice nursing is an integral component of British and New Zealand primary
      care, but in Australia it remains an emerging specialty. Despite an increased
      focus on the Australian practice nurse role, there has been limited strategic
      role development, particularly relating to national health priority areas. This
      paper reports the third stage of a Project exploring the Australian practice
      nurse role in the management of cardiovascular disease (CVD). This stage involved
      a consensus development conference, undertaken to identify strategic, priority
      recommendations for practice nurse role development. 1. Practice nurses have an
      important role in developing systems and processes for CVD management; 2. A
      change in the culture of general practice is necessary to promote acceptance of
      nurse-led CVD management; 3. Future research needs to evaluate specific models of
      care, incorporating outcome measures sensitive to nursing interventions; 4.
      Considerable challenges exist in conducting research in general practice; and 5.
      Changes in funding models are necessary for widespread practice nurse role
      development. The shifting of funding models provides evidence to support
      interdisciplinary practice in Australian general practice. The time is ripe,
      therefore, to engage in prospective and strategic planning to inform development
      of the practice nurse role.

PMID- 18041994
TI  - Time to talk, time to see: changing microeconomies of professional practice among
      nurses and doctors in Australian general practice.
AB  - In Australia, more nurses are entering general practice, and nurses' work is
      being funded in increasingly complex ways through Medicare. Little research has
      explored the ways doctors and nurses realign their priorities and activities when
      working together in general practice. We undertook rapid, intensive multimethod
      studies of 25 general practices to explore the ways in which the labour of nurses
      and doctors was structured, and the implicit decisions made by both professions
      about the values placed on different ways of working and on their time. Data
      collected included photographs, floor-plans, interviews with 37 nurses, 24
      doctors and 22 practice managers, and 50 hours of structured observation. Nursing
      time was constructed by both nurses and doctors as being fluid and non
      contingent; they were regarded as being 'available' to patients in a way that
      doctors were not. Compared to medical time, nursing time could be disposed more
      flexibly, underpinning a valorized attribute of nursing: deep clinical and
      personal contact with patients. The location of practice nurses' desks in areas
      of traffic, such as administrative stations, or in the treatment room,
      underpinned this valuable unstructured contact with patients. Changes to the
      practice nurse role through direct fee-for-service items for nurses may lead to
      greater congruence between the microeconomies of nursing and medicine in general
      practice. In a time of pressure upon a primary care workforce, this is likely to
      lead to more independent clinical work by nurses, but may also lead to a decrease
      in flexible contact with patients.

PMID- 18041995
TI  - Exploring the development of Australian general practice nursing: where we have
      come from and where to from here?
AB  - Significant development has occurred in the role and scope of Australian general
      practice nursing in the last decade. Although there has been a nursing presence
      in Australian general practice for many years (Linn 1977), current workforce
      shortages and the growing need for chronic and complex disease management and
      provision of preventive health care in the community have fuelled role
      development (Halcomb, Patterson & Davidson 2006). In an effort to explore and
      document the evolution of scholarship and professional development in Australian
      general practice nursing a content analysis of the proceedings of the four
      Australian practice nursing conferences was undertaken. This framework allows the
      mapping of the trajectory related to professional development issues, policy,
      research and scholarship. Content analysis revealed that the papers presented at
      each of the four conferences could be broadly divided into six major themes,
      namely: (1) role of the practice nurse, (2) education and training, (3) research,
      (4) legal, ethical and risk issues, (5) innovation in clinical practice, and (6)
      operational and management issues in general practice. Documenting the evolution
      of this emerging specialty is important in planning initiatives to maximise
      practice nurses' important contribution to primary health care.

PMID- 18041997
TI  - Discontinued drugs in 2006: anti-infectives.
AB  - Of the drugs dropped from development in 2006, 11 were being developed for
      infectious diseases. Of these, nine were for viral diseases, including four
      against HIV, two against hepatitis C virus and one each against respiratory
      syncytial virus, severe acute respiratory syndrome (coronavirus) and a variety of
      viruses. The nine antiviral agents comprised six synthetic small-molecule
      compounds, one peptide, one monoclonal antibody and a vaccine. The remaining two
      agents were a vaccine for Pseudomonas aeruginosa infection, and lipid-based agent
      for septic shock. Each of these drugs is briefly reviewed and reasons for failure
      are discussed.

PMID- 18041998
TI  - The potential link between atherosclerosis and the 5-lipoxygenase pathway:
      investigational agents with new implications for the cardiovascular field.
AB  - The 5-lipoxygenase pathway is responsible for the production of leukotrienes-
      inflammatory lipid mediators that have a role in innate immunity, but that can
      also have pathological effects in inflammatory diseases. Recently, a potential
      link between leukotriene production and atherosclerosis has been proposed. The
      expression of leukotriene biosynthetic enzymes and leukotriene receptors has been
      identified in coronary and carotid atherosclerotic plaques, and the levels of
      biosynthetic enzymes have been correlated with the clinical symptoms of unstable
      plaques. Genetic variants in 5-lipoxygenase pathway genes have also been
      associated with a relative risk of developing myocardial infarction and stroke.
      On the basis of these discoveries, antileukotriene compounds are now being
      evaluated for the treatment of cardiovascular disease. Several tool compounds
      have been shown to limit the progression of lesion development in preclinical
      models of atherosclerosis, and three compounds, including two drugs previously
      developed for asthma, are undergoing clinical trials in patients with acute
      coronary syndromes.

PMID- 18041999
TI  - Antiangiogenic agents for the treatment of glioblastoma.
AB  - Glioblastomas are highly vascularized and, therefore, antiangiogenic agents are
      increasingly being explored as therapeutic options. This review summarizes the
      present data on antiangiogenic agents in glioblastoma treatment. The angiogenic
      pathway in gliomas and the proposed mechanisms of antiangiogenic agents are
      reviewed briefly, and details of the drugs in clinical trial are provided. In
      addition to their effects on blood vessels, these agents also have potent
      antiedema effects that may have therapeutic benefit. The review concludes with a
      discussion of the role of biomarkers and neuroimaging in the assessment of tumor
      response. Although preliminary studies of these drugs in glioblastoma have been
      promising, larger prospective trials that include survival as an end point will
      be required to determine the ultimate utility of this class of agents. It seems
      likely that a combination of antiangiogenesis agents with other cytotoxic
      therapies will be required to achieve maximal efficacy.

PMID- 18042000
TI  - Leukotriene B4 receptor antagonists as therapeutics for inflammatory disease:
      preclinical and clinical developments.
AB  - Leukotriene B(4) (LTB(4)) is a lipid inflammatory mediator derived from membrane
      phospholipids by the sequential actions of cytosolic phospholipase A2 (PLA2), 5
      lipoxygenase (5-LO) and leukotriene A(4) (LTA(4)) hydrolase. Several inflammatory
      diseases, including asthma, chronic obstructive pulmonary disease, arthritis and
      inflammatory bowel disease, have been associated with elevated levels of LTB(4).
      As a result, pharmacological strategies to modulate the synthesis of LTB(4)
      (inhibition of PLA2, 5-LO or LTA(4) hydrolase) or the effects of LTB(4) itself
      (antagonism of LTB(4) receptors) are being developed by several companies. Two G
      protein-coupled receptors mediate the effects of LTB(4), namely BLT1 and BLT2.
      The pharmacology, expression and function of these two receptors were last
      reviewed by Tager and Luster in 2004. Since then, there has been an increased
      understanding of the function of these receptors, in particular for the lesser
      understood of the two receptors, BLT2. Furthermore, since last reviewed in 1996,
      there have been several clinical developments in the use of BLT receptor
      antagonists for inflammatory diseases. This review summarizes the latest
      preclinical and clinical developments in BLT antagonism for inflammatory diseases
      and discusses potential future developments.

PMID- 18042001
TI  - Natural antioxidants in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      characterised by severe cognitive impairment that ultimately leads to death.
      Current drugs used in AD are acetylcholinesterase inhibitors and antagonists to
      the NMDA receptors. These drugs may only slightly improve cognitive functions but
      have only very limited impact on the clinical course of the disease. In the past
      several years, based on in vitro and in vivo studies in laboratory animals,
      natural antioxidants, such as resveratrol, curcumin and acetyl-L-carnitine have
      been proposed as alternative therapeutic agents for AD. An increasing number of
      studies demonstrated the efficacy of primary antioxidants, such as polyphenols,
      or secondary antioxidants, such as acetylcarnitine, to reduce or to block
      neuronal death occurring in the pathophysiology of this disorder. These studies
      revealed that other mechanisms than the antioxidant activities could be involved
      in the neuroprotective effect of these compounds. This paper discusses the
      evidence for the role of acetylcarnitine in modulating redox-dependent mechanisms
      leading to the upregulation of vitagenes. Furthermore, future development of
      novel antioxidant drugs targeted to the mitochondria should result in effectively
      slowing disease progression. The association with new drug delivery systems may
      be desirable and useful for the therapeutic use of antioxidants in human
      neurodegenerative diseases.

PMID- 18042002
TI  - Huntington's disease: progress and potential in the field.
AB  - While the first description of Huntington's disease was reported over a century
      ago, no therapy exists that can halt or ameliorate the inexorable disease
      progression. Tremendous progress, however, has been made in significantly
      broadening the understanding of pathogenic mechanisms in this neurological
      disorder that may eventually lead to successful treatment strategies.
      Huntington's disease is caused by the expansion of a CAG repeat in the huntingtin
      gene, which results in the expression of a mutant form of the protein that is
      toxic to neurons. Several mechanisms have been identified in mediating this
      toxicity, such as protein aggregation, mitochondrial dysfunction, oxidative
      stress, transcriptional dysregulation, aberrant apoptosis, altered proteosomal
      function and excitotoxicity. With increasing understanding of each of these
      pathogenic mechanisms, therapeutic strategies have attempted to target specific
      aspects of each. There have been many encouraging reports of preclinical efficacy
      in transgenic Huntington's disease mice, from which a number have been extended
      to human clinical trials with some success. This review focuses on these studies
      and the compounds that hold promise for treating human Huntington's disease.

PMID- 18042003
TI  - Silodosin, a novel selective alpha 1A-adrenoceptor selective antagonist for the
      treatment of benign prostatic hyperplasia.
AB  - Silodosin is a novel selective alpha(1A)-adrenoceptor (AR) antagonist generated
      by Kissei Pharmaceutical Co. Ltd. This drug selectively binds to alpha(1A)-AR,
      which is widely distributed in the prostate, urethra and bladder trigone,
      involved in their contraction, located at the lower urinary tract. This high
      selectivity for alpha(1A)-AR contributes to inhibition of sympathetic nerve
      stimulation and relaxation of smooth muscle tone of the lower urinary tract
      tissues, resulting in suppression of increase in intraurethral pressure. Clinical
      data suggested that silodosin showed significant improvement in lower urinary
      tract symptoms associated with benign prostatic hyperplasia, as well as in
      quality of life. The improvements were observed in both voiding and storage
      symptoms. In addition, the clinical effects occurred in the early treatment
      phase, and were observed not only in mild cases, but also in cases with severe
      symptoms. Long-term study revealed that the efficacy and safety was sustained for
      1 year. Although silodosin showed relatively high incidence rate of abnormal
      ejaculation, the adverse events associated with lowering of blood pressure were
      low. This article reviews preclinical and clinical data of silodosin, and
      introduces the usefulness of the drug for treatment of benign prostatic
      hyperplasia patients.

PMID- 18042004
TI  - The role of azacitidine in the treatment of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic
      disorders characterized by ineffective hematopoiesis and potential transformation
      to acute myeloid leukemia. Supportive care including transfusions and growth
      factors remained the mainstay of treatment for decades; however, further
      understanding of the biology behind these diseases led to the investigation of
      novel agents. As hypermethylation of tumor suppressor genes, such as p15, was
      believed to play a key role in the pathogenesis of these diseases,
      hypomethylating agents were investigated. Azacitidine is one of two
      hypomethylating agents used in the treatment of MDS, and the first approved by US
      FDA. In preclinical studies, azacitidine demonstrated
      hypomethylating/differentiating activity with low concentration, whereas high
      concentration was associated with cytotoxic effects. In clinical trials,
      azacitidine not only improved the cytopenias associated with MDS but also delayed
      leukemic transformation, improved quality of life and improved overall survival
      in many patients so treated. Azacitidine was the first agent noted to change the
      natural history of the disease. Further studies are underway evaluating the role
      of azacitidine pre- and post-transplantation, in combination with other agents,
      as well as in treatment of acute myeloid leukemia patients who are not good
      candidates for intensive chemotherapy. Azacitidine is also likely to be studied
      in the treatment of other malignant conditions. Although both subcutaneous and
      intravenous administrations have been approved, oral azacitidine is presently
      under investigation.

PMID- 18042005
TI  - Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of
      chemotherapy-induced nausea and vomiting.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is a distressing and common
      adverse event associated with cancer treatment. Updated anti-emetic guidelines
      were published in 2007 by the National Comprehensive Cancer Network and in 2006
      by the American Society of Clinical Oncology, which have included the use of the
      new and more effective anti-emetic agents (5-hydroxytryptamine-3 [5-HT(3)]
      receptor antagonists and neurokinin-1 [NK-1] receptor antagonists). Aprepitant is
      a selective NK-1 receptor antagonist approved as part of combination therapy with
      a corticosteroid and a 5-HT(3) receptor antagonist for the prevention of acute
      and delayed CINV. Fosaprepitant (also known as MK-0517 and L-758,298) is a water
      soluble phosphoryl prodrug for aprepitant, which, when administered
      intravenously, is converted to aprepitant within 30 min after intravenous
      administration via the action of ubiquitous phosphatases. Because fosaprepitant
      is rapidly converted to the active form (aprepitant), it is expected to provide
      the same aprepitant exposure in terms of AUC, and a correspondingly similar anti
      emetic effect. Clinical studies have suggested that fosaprepitant could be
      appropriate as an intravenous alternative to the aprepitant oral capsule. In a
      study in healthy subjects, fosaprepitant was well tolerated up to 150 mg (1
      mg/ml), and fosaprepitant 115 mg was bioequivalent in its AUC to aprepitant 125
      mg. Fosaprepitant 115 mg has been submitted for FDA approval as an alternative on
      day 1 of a 3-day oral aprepitant regimen, with oral aprepitant administered on
      days 2 and 3. Fosaprepitant may be a useful parenteral alternative to oral
      aprepitant. Further study is needed to clarify the use of fosaprepitant for the
      prevention of CINV, and to clarify optimal dosing regimens that may be
      appropriate substitutes for oral aprepitant.

PMID- 18042006
TI  - An update on the pharmacology of galantamine.
AB  - Alzheimer's disease (AD) is associated with a gradual loss of attention and
      memory that has been related to impairment of brain cholinergic
      neurotransmission, particularly a deficit of cholinergic neurons. The first
      therapeutic target that has demonstrated therapeutic efficacy on cognition,
      behaviour and functional daily activities has been the inhibition of
      acetylcholinesterase. The acetylcholinesterase inhibitors used to treat AD
      patients at present are donepezil, rivastigmine and galantamine. This review
      summarises the current state of the art concerning the pharmacology of
      galantamine, focusing on the most important details of its possibilities as an
      acetylcholinesterase inhibitor, an allosteric potentiator of neuronal nicotinic
      receptors for acetylcholine, a modulator of neurotransmitter release, and an
      agent causing neuroprotection through an antiapoptotic action. In so doing,
      galantamine will be discussed in the context of the treatment of dementia, both
      of AD type and of mixed vascular-Alzheimer type.

PMID- 18042007
TI  - A review of the efficacy and tolerability of agomelatine in the treatment of
      major depression.
AB  - Agomelatine is a novel agent that is under late-stage development as a potential
      antidepressant. Compared with available antidepressant agents, the drug may have
      a distinct mechanism of action, with significant interactions with melatonin
      receptors, in addition to serotonergic brain systems. Agomelatine has been shown
      to be active in preclinical models indicative of antidepressant activity and the
      results of a large-scale clinical trial programme, conducted in major depressive
      disorder, indicate both antidepressant activity and a favourable tolerability
      profile. As agomelatine may have a pharmacological profile and mechanism of
      action distinct from available agents, it may come to represent a valuable
      additional treatment option in those patients who do not respond fully or who
      prove unable to tolerate the side effects of existing antidepressants.

PMID- 18042008
TI  - Menopausal hormone therapy for vasomotor symptoms: balancing the risks and
      benefits with ultra-low doses of estrogen.
AB  - Estrogen therapy is the most consistently effective treatment and the only
      therapy approved by the FDA for menopausal vasomotor symptoms. Following the
      safety issues reported in the primary Women's Health Initiative publications and
      with continued patient requests for treatment, a challenge to clinicians has been
      to identify the lowest effective dose of estrogen for alleviating menopausal
      symptoms. A number of low-dose estrogen preparations are now available, and
      transdermal preparations containing an ultra-low dose (25% of the previous
      conventional or standard dose) of estrogen have recently been approved by the
      FDA. These preparations effectively relieve menopausal symptoms such as vasomotor
      symptoms and vaginal atrophy, and potentially protect against bone loss. Compared
      with standard-dose estrogen therapy, these ultra-low-dose products have an
      improved tolerability profile and may require reduced amounts or a lower
      frequency of progestogen administration, potentially mitigating the apparent long
      term adverse effects of estrogen-progestogen combinations, as noted in the
      Women's Health Initiative.

PMID- 18042010
TI  - Extracorporeal shockwave lithotripsy (ESWL): a chronology.

PMID- 18042011
TI  - Low-dose computed tomography for the evaluation of flank pain in the pregnant
      population.
AB  - BACKGROUND: Evaluation of the pregnant patient with suspected renal colic is
      complex. Fetal irradiation concerns have traditionally prohibited the use of CT
      in this population. We report our institution's experience using low-dose CT in
      the evaluation of pregnant patients with refractory flank pain. PATIENTS AND
      METHODS: A retrospective review of all patients who underwent low-dose CT
      evaluation of the urinary tract for suspected urinary tract stones was performed.
      Data obtained included gestational age, urinalysis and ultrasonography results,
      CT findings, and calculated fetal radiation exposure. RESULTS: Between April 2004
      and December 2006, 20 patients with an average gestational age of 26.5 weeks
      presented to our institution with acute, refractory flank pain consistent with a
      diagnosis of urolithiasis. All patients underwent renal ultrasonographic
      evaluation before unenhanced CT of the abdomen and pelvis using a low-dose
      protocol. The average radiation exposure was 705.75 mrads (range 210-1372; SD +/-
      338.66 mrads). Of the 20 patients, CT demonstrated urinary stones (1-12 mm) in
      13. Of those patients with documented stones, 4 were treated conservatively, 2
      underwent intrapartum stent placement, 5 had ureteroscopy with stone extraction,
      and 2 were treated postpartum. CONCLUSION: Low-dose CT is highly sensitive and
      specific for the detection of urinary calculi in the pregnant population. CT
      confers a low risk of fetal harm and can improve patient care when used
      judiciously.

PMID- 18042012
TI  - Stone treatment index: a mathematical summary of the procedure for removal of
      stones from the urinary tract.
AB  - BACKGROUND AND PURPOSE: Numerous factors influence the treatment result and
      efforts for stone removal. To summarize the important factors, our aim was to
      formulate a general mathematical expression of the stone-removal procedure.
      MATERIALS AND METHODS: A mathematical expression (stone treatment index; STI) was
      developed for patients who became stone free (SF): STI(SF) = (Num(SF) x mean(sqrt
      [SA] x HI) x meanAge(R) x meanBMI(R) x (1 + meanNum(ANA)) divided by
      Num(SESSIONS) + Num(AUX) + Num(ANE) + Num(COMP). The variables included were the
      number of stone-free patients (Num(SF)), mean stone burden expressed as the
      product of the square root of the stone surface area (SA(1/2)) and the hardness
      index (HI), the mean age ratio (Age(R) = age/50), the mean body mass index (BMI)
      ratio (BMI(R) = BMI/25), the mean number of patients with anatomic abnormalities
      (Num(ANA)), the total number of treatment sessions (Num(SESSIONS)), the number of
      auxiliary procedures (Num(AUX)), the number of procedures requiring general or
      regional anesthesia (Num(ANE)), and the number of complications (Num(COMP)). A
      similar index was calculated for patients who were either stone free or had
      residual fragments < or =4 mm (STI(DIS)). For conclusions on efficacy, these
      indices were compared with optimal and total values of STI. The STI was
      calculated for 450 patients with renal and 374 patients with ureteral stones
      treated with shockwave lithotripsy as the primary procedure. In patients with a
      known BMI, this factor was used; otherwise, the BMI(R) was set to 1. RESULTS:
      When STI was compared with the efficiency quotient (EQ) for stones in different
      size intervals, STI was less sensitive to variations in stone burden. The
      quotients STI(SF)/STI(OPTIMAL) corresponded roughly to EQ but might be more
      informative because of the inclusion of factors for anesthesia and complications.
      CONCLUSION: With or without related estimates, the STI might be useful for
      summarizing stone-removal procedures in groups or individual patients with
      urinary-tract stones. The STI might be helpful because it encompasses the factors
      of importance for conclusions about the treatment procedure, such as the hardness
      of the stone, the age and body size of the patient, and the presence of anatomic
      abnormalities likely to influence the result. The STI might be used
      advantageously for comparison of different equipment and treatment strategies.

PMID- 18042013
TI  - Percutaneous renal access: a simplified approach.
AB  - PURPOSE: To present a simplified surgical technique to access the kidney
      percutaneously with low exposure to radiation. MATERIAL AND METHODS: This
      percutaneous approach to the kidney "creates" a plane of coincidence between the
      C-arm beam axis and the needle axis. Both axes always have the same angle running
      in opposite directions with the predetermined calix located in the medial
      vertical plane at 0 degrees. Twenty-one percutaneous access tracts were made into
      the lower calix and 7 into the middle and upper calices. The 3-dimensional
      position of the inserted needle was determined. RESULTS: All tracts were
      successfully accomplished. Statistical analysis of 28 procedures revealed that
      the technique is reproducible. The coefficient of variation of the angle
      determining the entrance position of the needle was low, which indicated that the
      procedure is reproducible and easy to teach. CONCLUSION: The technique is safe,
      easy to perform, reproducible, and requires less radiation than other methods.

PMID- 18042014
TI  - Prestenting improves ureteroscopic stone-free rates.
AB  - PURPOSE: Although the use of stents after ureteroscopy has been studied
      extensively, relatively little has been published about stent placement before
      complicated ureteroscopic procedures. In this study, we examined our experience
      with stent placement before ureteroscopic management of renal and ureteral stone
      disease. PATIENTS AND METHODS: A total of 90 patients underwent ureteroscopic
      surgery on 115 renal units by a single surgeon from 2001 to 2006. All patients
      had documented follow-up with imaging either by CT or intravenous urography (IVU)
      with tomography. Patients were classified into two groups depending on whether
      they had a stent placed before ureteroscopy. Baseline characteristics, operative
      indications for stent placement, stone-free rates, and complications were
      compared between groups. RESULTS: Baseline characteristics were similar between
      the groups. The majority of patients received stents before stone management
      because of technical considerations during surgery (17/36, 47%) or infection
      (13/36, 37%). Strict stone-free rates after ureteroscopic treatment were 47% in
      the 79 procedures without previous stents, compared with 67% in the 36 procedures
      with prestenting (P < 0.05). Including small fragments (2 mm or smaller), stone
      free rates improved to 54% v 78%, respectively (P < 0.02). Complications were not
      significantly different in the two groups (P = 0.70). CONCLUSION: Although
      routine stent placement is not necessary before all ureteroscopic procedures, we
      demonstrate that it is associated with good stone-free rates and few
      complications. In this retrospective cohort, prestenting was associated with
      significantly higher stone-free rates. Prestenting should be considered in
      challenging cases.

PMID- 18042015
TI  - One-step percutaneous nephrostomy in patients with a history of open
      nephrolithotomy: comparison with the fascial dilator system.
AB  - BACKGROUND AND PURPOSE: A percutaneous nephrostomy (PCN) done on the same side as
      a previous open nephrolithotomy is always technically challenging. A novel one
      step PCN tube that allows the puncture and placement of a drainage tube to be
      done in a single step has been developed. The hydrophilic coating on the tube's
      surface significantly reduces friction and allows easier insertion. We evaluated
      the tube's efficiency and safety compared with the traditional fascial dilator
      system. PATIENTS AND METHODS: Sixty-five patients with a history of open
      nephrolithotomy were randomly allocated (with the aid of a computer-derived
      assignment number) into two groups to have PCN performed in one step or multiple
      steps. In the one-step group, a new type of PCN tube was used. In the multistep
      group, fascial dilators were used serially prior to tube insertion. The two
      groups were similar in terms of mean age, width of target calix, and baseline
      serum creatinine and hemoglobin concentrations. The operating times, intubation
      rates, and complications in the two groups were compared. RESULTS: The mean
      number of attempts required to access the collecting system was 1.1 +/- 0.6 in
      the one-step group v 2.3 +/- 1.2 in the multistep group (P = 0.002), the
      successful intubation rate was 96.9% v 78.8% (P = 0.012), the mean operating time
      was 10.2 +/- 2.4 minutes v 25.6 +/- 2.8 minutes (P = 0.029), and the rate of
      intraoperative and postoperative complications was 3.1% v 15.2%, respectively (P
      = 0.019). No major complications occurred in the one-step group. CONCLUSIONS: The
      one-step PCN tube is a convenient and efficacious method for accessing an
      anatomic region where open nephrolithotomy was done previously and is a simple
      method for nephrostomy tube placement.

PMID- 18042016
TI  - Practice patterns of ureteral stenting after routine ureteroscopic stone surgery:
      a survey of practicing urologists.
AB  - BACKGROUND: Controversy exists regarding the need for ureteral stent insertion
      after routine ureteroscopic stone surgery. We designed a questionnaire to assess
      and better understand the practice patterns of urologists for stent applications.
      MATERIALS AND METHODS: A 26-question survey was distributed to 570 community and
      academic urologists. The answers were anonymously tabulated to determine the
      practice patterns for stent placement. RESULTS: Of the 173 respondents, 97.7%
      performed ureteroscopic surgery, with the majority (77%) performing 1 to 10
      procedures per month. Sixty-eight percent of urologists considered more than 70%
      of their ureteroscopic procedures "routine." Only 21% of urologists dilated the
      ureteral orifice more than 90% of the time. Those who dilated the ureteral
      orifice used a balloon (43%), ureteral access sheath (13.5%), or both (21%). The
      use of an access sheath did not change stenting practices for 75% of urologists.
      Patterns vary with regard to length of indwelling time, with 85% of urologists
      maintaining the stent for fewer than 7 days. Most urologists use either
      cystoscopy (42%) or pull-suture in clinic (37%) to remove stents. Patient
      tolerance is the most significant problem with stents reported by 97.6% of
      urologists. The respondents were divided into three experience-based groups:
      group 1, <2 years of experience; group 2, 2 to 10 years; and group 3, >10 years.
      Using Fisher's exact test, there were no statistically significant differences
      between the groups. CONCLUSION: A wide variability exists among urologists in the
      practice patterns of stent insertion after routine ureteroscopic surgery. Most
      consider their procedures routine and are more likely to place stents after
      ureteral dilation despite growing evidence to the contrary. Knowledge of the
      varied practices may aid less experienced urologists in their decision to insert
      a stent after ureteroscopy.

PMID- 18042017
TI  - Occult spinal dysraphism and urolithiasis: are patients at higher risk of stone
      disease?
AB  - BACKGROUND AND PURPOSE: Spinal dysraphism is associated with urinary-tract
      dysfunction in severe cases such as meningomyelocele, in part because of
      incomplete innervation of the lower urinary tract. Patients with meningomyelocele
      are at higher risk for stone formation, possibly secondary to stasis of urine
      from aberrant storage and emptying. However, minimal data exist on the risk of
      stone formation in patients with milder forms of spinal dysraphism. The purpose
      of this study was to examine whether an association exists between urolithiasis
      and occult spinal dysraphism (OSD). PATIENTS AND METHODS: All patients who
      underwent a non-contrast CT scan of the abdomen and pelvis during a 4-month
      period were included. The final dataset consisted of 374 consecutive patients
      (195 men, 179 women) with a mean age of 54.2 years (range 18-95 years). Scans
      were reviewed for evidence of urolithiasis and, independently, for skeletal
      abnormalities. Patients with urolithiasis included those with a kidney, ureteral,
      or bladder stone(s). Patients with OSD included those with bifid lumbosacral bony
      elements, posterior arch defects, or incomplete fusion or non-fusion of S1, S2,
      or S3. The association between urolithiasis and OSD was examined by calculating
      series of crude and adjusted odds ratios (ORs) with corresponding 95% confidence
      intervals (CIs). RESULTS: Of the 374 patients, 135 (36.1%) had urinary calculi,
      and 83 (22.2%) had OSD. No relation was found between the prevalence of OSD and
      stone disease (OR 1.22; 95% CI 0.72, 2.08), even after adjusting for potential
      confounders. CONCLUSION: Unlike severe spinal dysraphism, OSD does not appear to
      confer an increased risk of stone disease.

PMID- 18042018
TI  - Percutaneous nephrostomy in patients with tumors of advanced stage: treatment
      dilemmas and impact on clinical course and quality of life.
AB  - OBJECTIVES: The purpose of this study was to evaluate the outcome, in respect to
      safety, survival, and quality of life (QoL), after performance of percutaneous
      nephrostomy in patients with obstructive nephropathy caused by various types of
      advanced malignancy. PATIENTS AND METHODS: A cohort of 270 patients with
      established nephropathy because of advanced pelvic or nonpelvic tumors was
      evaluated. A decision to obtain percutaneous access was made; primary stenting
      had either failed or was not feasible because of complicated anatomy. Patients
      were divided in equal groups by type of malignancy (54 patients each). In
      addition, each malignancy group was further divided in two equal subgroups by
      tumor burden (27 patients each). Correlations were made with respect to renal
      function outcome, overall survival after the procedure, and QoL differences both
      before and after the procedure. RESULTS: No serious complications, such as severe
      bleeding or sepsis, were experienced because of the procedure. Statistical
      analysis showed no significant differences in survival among patients with
      different types of cancer. Only patients with prostate (P < 0.0365) and
      colorectal (P < 0.0307) cancer with lower tumor burden had significantly longer
      survival when compared with patients with large tumor burden. Regarding QoL
      scores, only patients with prostate cancer in the subgroup with low tumor burden
      demonstrated a positive statistically significant difference (P < 0.001).
      CONCLUSIONS: Despite the fact that percutaneous nephrostomy has shown good safety
      characteristics and beneficial impact on renal function, only patients with
      specific cancers most likely to respond to ongoing palliative therapy or with
      cancers that progress slowly by nature may statistically benefit from the
      procedure. This questions the universal application of this procedure for all
      types and stages of advanced malignancy.

PMID- 18042019
TI  - Advances in pheochromocytoma management in the era of laparoscopy.
AB  - PURPOSE: To understand the advances that were made in the management of
      pheochromocytoma since laparoscopy was initiated at our institution. MATERIALS
      AND METHODS: Data for all patients who underwent surgical procedure for adrenal
      diseases had been recorded prospectively since September 2000, when laparoscopy
      was routinely initiated at our institution; all patients with a diagnosis of
      pheochromocytoma up to December 2005 had their data assessed (group 1). Charts
      for all patients with a diagnosis of pheochromocytoma who underwent surgery at
      our institution from 1990 to 1995 (group 2) were reviewed, and the data were
      compared with data from patients in group 1. RESULTS: In group 1, 24 patients
      with pheochromocytoma underwent 26 procedures at our institution, including five
      patients with extra-adrenal tumor and one patient with bilateral tumor; 18
      adrenalectomies (one bilateral) were performed, and two extra-adrenal tumors were
      removed using a laparoscopic approach. In group 2, ten open adrenalectomies were
      performed in 9 patients (1 bilateral). The patients who underwent laparoscopy for
      either adrenal or extra-adrenal tumor had shorter operative times and hospital
      stay and less bleeding. CONCLUSIONS: Pheochromocytoma is a complex disease with
      potentially severe complications. Laparoscopic adrenalectomy can be safely
      performed for removal of either adrenal or extra-adrenal tumors. Patients spend a
      shorter time in the critical care unit after the procedure.

PMID- 18042020
TI  - Laparoscopic nephrectomy outcomes of elderly patients in the 21st century.
AB  - BACKGROUND AND PURPOSE: As life expectancy continues to increase, we will be
      faced with the need to counsel older patients on the risks and benefits of
      undergoing surgery. It is clear that laparoscopic renal surgery has significant
      benefits over open renal surgery. However, contemporary data on whether these
      benefits carry over to the elderly is less robust. The objective of this study is
      to compare the perioperative outcomes of laparoscopic nephrectomy in patients age
      70 and over to those under age 70. Outcomes from the study can be used to assist
      in preoperative counseling for older patients. PATIENTS AND METHODS: Between
      February 2000 and December 2005, 405 consecutive patients underwent laparoscopic
      nephrectomy for benign or malignant conditions. To decrease selection bias,
      kidney donors, bilateral nephrectomies, partial nephrectomies, as well as
      patients under the age of 17 were excluded. Laparoscopic nephrectomies included
      simple nephrectomies, radical nephrectomies, and nephroureterectomies. A total of
      158 patients were included in the analysis. Patient demographics and
      perioperative data were recorded prospectively. The preoperative American Society
      of Anesthesiologists (ASA) score was used to reflect patient co-morbidity. Subset
      analysis between pure laparoscopic nephrectomy (LN) and hand-assisted
      laparoscopic nephrectomy (HALN) was also performed. RESULTS: Average hospital
      stay for patients 70 years and older was 3.6 days versus 2.6 days for their
      younger counterparts (p = 0.02). All other demographic and perioperative
      parameters were comparable between groups, including incidence of intraoperative
      or postoperative complications, blood transfusions, and conversions to open
      surgery. In a subset analysis of patients undergoing HALN, despite having similar
      co-morbid conditions (ASA score 2.57 vs. 2.56, p = 0.9), the elderly group had a
      significantly increased length of stay compared to patients younger than 70 years
      (3.0 vs. 4.2 days, p < 0.05). However, in the group undergoing LN, there was no
      statistically significant difference in hospital stay (3.1 vs. 2.4 days, p =
      0.22), despite the older group having higher co-morbid conditions (ASA score 2.55
      vs. 2.10, p < 0.01). CONCLUSION: Other than an increased hospital stay by one
      day, patients 70 years and older undergoing laparoscopic nephrectomy can expect
      comparable perioperative outcomes to those achieved in younger patients. Such
      differences in the length of hospital stay may be mitigated by pure laparoscopic
      nephrectomy as opposed to hand-assisted laparoscopic nephrectomy in patients 70
      years or older. These data may be useful in preoperative decision-making and
      counseling in this growing subset of patients.

PMID- 18042021
TI  - Robot-assisted urologic surgery: safety and feasibility in the pediatric
      population.
AB  - PURPOSE: To assess the safety and feasibility of performing robot-assisted
      pediatric urologic surgery with the da Vinci Surgical System (Intuitive Surgical,
      Inc, Sunnyvale, Calif) based on our experience with a variety of procedures.
      PATIENTS AND METHODS: A retrospective review was performed of 53 robot-assisted
      pediatric procedures performed in our practice between September 2003 and March
      2006. The procedures included 11 renal extirpative surgeries, 10 orchiopexies, 26
      dismembered pyeloplasties, 2 uretero-ureterostomies, and 3 bladder surgeries. The
      mean patient age was 7.7 years, and the mean patient weight was 32 kg. All
      procedures were performed transperitoneally. RESULTS: All procedures were
      successfully completed with no conversions to open surgery. There was one
      procedure in which the robotic system malfunctioned, resulting in an
      unrecoverable loss of three-dimensional visualization and temporary loss of
      color. The only postoperative complication involved delayed return of bowel
      function that led to a diagnostic laparotomy with negative findings. A decrease
      in mean postoperative stay was noted in patients who underwent robot-assisted
      procedures compared with previous patients who had undergone open surgery.
      CONCLUSION: Robot-assisted surgery appears to be safe and feasible for a variety
      of pediatric urologic procedures. Prospective randomized studies are required to
      further evaluate the outcomes compared with open surgical procedures. Our initial
      experience has been encouraging and will serve as a foundation for future and
      more complex minimally invasive pediatric urologic operations.

PMID- 18042022
TI  - How to improve the safety of polymer clips for vascular control during
      laparoscopic donor nephrectomy.
AB  - PURPOSE: To evaluate the use of a new modification of the technique for
      controlling the renal pedicle during laparoscopic donor nephrectomy (LDN) with
      Hem-o-Lok clips. PATIENTS AND METHODS: From July 2005 to January 2007, 241
      candidates for left LDN were enrolled in the study. There were 175 men, and the
      mean age of the patients was 27.84 +/- 4.96 years. At the end of procedure for
      renal-artery closure, one 10-mm Hem-o-Lok clip was applied a few millimeters
      distal to the root from the aorta, and a medium-large titanium clip was applied
      distal to the Hem-o-Lok clip using a non-automatic firing applier to exert
      sufficient closing pressure to the titanium clip to ensure adequate tightness.
      Then the renal vein was doubly ligated with one 12-mm and one 10-mm Hem-o-Lok
      clip. RESULTS: With these modifications, there were no intraoperative or
      perioperative bleeding complications, clip dislodgments, or slippages. The
      conversion rate was zero, and the mean warm-ischemia time was 7.50 +/- 0.71
      minutes (range 3-17 minutes). Graft function was excellent, with a mean serum
      creatinine concentration of 1.42 +/- 0.46 mg/dL after 12 months of follow-up and
      no renal-artery or -vein thrombosis in any of the grafts. CONCLUSION: With this
      technique, there is more security on the arterial closure, and sufficient pedicle
      length can be obtained for anastomosis. The warm-ischemia time is within an
      acceptable range. Also, this approach is less expensive than the use of
      endovascular staplers.

PMID- 18042023
TI  - Laparoscopic nephrectomy for benign and inflammatory conditions.
AB  - OBJECTIVES: To evaluate the outcomes of laparoscopic nephrectomy for benign renal
      conditions associated with dense perinephric inflammation, such as
      xanthogranulomatous pyelonephritis (XGPN), pyonephrosis, tuberculous
      pyelonephritis, and calculus pyelonephritis, and compare outcomes with a matched
      group of patients undergoing open nephrectomy for similar indications. An
      additional objective was to evaluate factors predictive of complications and open
      conversions. PATIENTS AND METHODS: We retrospectively analyzed data from 84
      patients with benign inflammatory diseases who underwent laparoscopic nephrectomy
      and compared the data with data from 94 matched patients undergoing open
      nephrectomy. Both groups were compared with regard to operative time, blood loss,
      intraoperative and postoperative complications, analgesia requirement, blood
      transfusion, and hospital stay. Univariate analysis assessed the predictive value
      of factors such as kidney size, presence of hilar lymphadenopathy, perinephric
      and perihilar adhesion, laterality and body mass index on complications and risk
      of open conversion. RESULTS: Mean operative time was 170 +/- 59.8 and 148 +/-
      42.5 minutes, blood loss was 156.2 +/- 6.8 and 154.6 +/- 68.8 mL, analgesia
      requirement was 165 +/- 71.2 and 284 +/- 81 g diclofenac sodium, and average
      hospital stay was 4.34 +/- 0.8 and 8.07 +/- 1.8 days in the laparoscopic and open
      groups, respectively. Abnormal renal hilum (71%) and perihilar adhesions (86%)
      were common findings in patients with XGPN, whereas abnormal hilum and hilar
      lymphadenopathy (55%) were commonly seen in those with tuberculosis. The renal
      hilum was relatively unaffected in patients with pyonephrosis and calculus
      pyelonephritis. Pleural entry was more common (P < 0.0001) in the open group, and
      visceral injury was more common in the laparoscopic group (P = 0.04). Blood
      transfusion was necessary in 7% and 11% of patients in the laparoscopic and open
      groups, respectively. Open conversion was required in 8 cases (autosomal dominant
      polycystic kidney disease-3, pyonephrosis, 2, XGPN and calculus pyelonephritis,
      3). Intestinal obstruction that required laparotomy and adhesinolysis developed
      in one patient in the laparoscopic group. CONCLUSION: Laparoscopic nephrectomy
      can be performed safely in most patients with benign inflammatory conditions that
      require surgical extirpation. Proper patient selection and technical
      modifications may help reduce morbidity. One should keep a low threshold for
      laparoscopic-assisted open conversion whenever necessary.

PMID- 18042024
TI  - Perirenal venous aneurysm presenting as retroperitoneal tumor treated
      successfully by laparoscopic excision.
AB  - We describe an unusually located venous aneurysm found incidentally in a 46-year
      old man that was presumptively diagnosed as a retroperitoneal mass near the left
      renal hilum. He presented for constipation and weight loss; an abdominal
      ultrasound scan disclosed an anechoic lesion in the left retroperitoneum.
      Abdominal CT showed a 3-cm mass with low density located at the junction of the
      left para-aortic and perirenal hilar regions that was initially suspected of
      being metastatic lymphadenopathy with an unknown primary origin or a neurogenic
      tumor. The mass was resected by a laparoscopic approach, which revealed a round
      mass with a smooth capsule and roots connecting to the paraspinal muscles. On
      pathologic examination, the mass showed classic features of a venous aneurysm. At
      12-month follow-up, no local recurrence or malignancy was documented.

PMID- 18042025
TI  - Predictive factors for open conversion of laparoscopic adrenalectomy: a 13-year
      review of 456 cases.
AB  - BACKGROUND AND PURPOSE: Laparoscopic adrenalectomy has largely replaced open
      adrenalectomy for the treatment of adrenal tumor. However, certain cases still
      require conversion to open procedures. Identifying the risk of conversion remains
      difficult. This study identified risk factors that may predict conversion from a
      laparoscopic to an open procedure. PATIENTS AND METHODS: From January 1993 to
      September 2006, a total of 456 laparoscopic adrenalectomies were performed at two
      urologic centers. A retrospective analysis of parameters, including tumor size,
      patient age, American Society of Anesthesiology classification, body mass index
      (BMI), sex, laparoscopic approach, previous abdominal surgery, laterality, type
      of tumor, laparoscopist experience, and surgeon, was performed. Multivariate
      logistic regression was used to identify those variables predicting conversion.
      RESULTS: A total of 25 (5.5%) laparoscopic adrenalectomies required conversion.
      Significant predictors of conversion according to univariate analysis were tumor
      size > or =5 cm, BMI > or =24 kg/m(2), and pheochromocytoma. Multivariate
      analysis showed that the significant independent predictive factors for
      conversion were tumor size > or =5 cm (8.884 greater odds ratio [OR] of
      conversion; 95% confidence interval 3.543, 22.277; P < 0.001), BMI > or = 24
      kg/m(2) (OR 3.632; 95% confidence interval 1.367, 9.648; P = 0.010), and
      pheochromocytoma (OR 3.068; 95% confidence interval 1.175, 8.007; P = 0.022).
      CONCLUSIONS: Knowledge of tumor size, BMI, and tumor type can help in counseling
      patients undergoing laparoscopic adrenalectomy with regard to the probability of
      conversion. The size of the tumor was found to be the most important predictor.

PMID- 18042026
TI  - Case report: percutaneous cryoablation of a small renal lesion necessitating
      modified lateral decubitus position.
AB  - When performing percutaneous cryoablation for renal masses, the standard patient
      positioning has been the prone position. We present a case in which placing the
      patient in a modified lateral decubitus position aided in the access of probe
      placement for percutaneous cryoablation.

PMID- 18042027
TI  - Da Vinci robot error and failure rates: single institution experience on a single
      three-arm robot unit of more than 700 consecutive robot-assisted laparoscopic
      radical prostatectomies.
AB  - BACKGROUND AND PURPOSE: Previous reports have suggested that a 2% to 5% device
      failure rate (FR) be quoted when counseling patients about robot-assisted
      laparoscopic radical prostatectomy (RLRP). We sought to evaluate our FR on the da
      Vinci system. PATIENTS AND METHODS: Since February 2003, more than 800 RLRPs have
      been performed at our institution using a single three-armed robotic unit. A
      prospective database was analyzed to determine the device FR and whether it
      resulted in case abortion or open conversion. Intuitive Surgical Systems provided
      data concerning the system's performance, including its fault rate. Error
      messages were classified as recoverable and non-recoverable faults. RESULTS:
      Between February 2003 and November 2006, 725 RLRP cases were available for
      evaluation. There were no intraoperative device failures that resulted in a case
      conversion. Technical errors resulting in surgeon handicap occurred in 3 cases
      (0.4%). Four patients (0.5%) had their procedures aborted secondary to system
      failure at initial set-up prior to patient entrance to the operating room. Data
      analysis retrieved from the da Vinci console reported on a total of 807
      procedures since 2003. Only 4 cases (0.4%) were reported from the Intuitive
      Surgical database to result in either an aborted or a converted case, which
      compares favorably with our results. Since the last computer system upgrade
      (September 2005), the mean recoverable and non-recoverable fault rates per
      procedure were 0.21 and 0.05, respectively. CONCLUSIONS: For all the advanced
      features the da Vinci system offers, it is surprisingly reliable. Throughout our
      RLRP experience, device failure resulted in case conversion, procedure abortion,
      and surgeon handicap in 0, 0.5%, and 0.4% of procedures, respectively. As such, a
      lowered device FR of 0.5% should be used when counseling patients undergoing
      RLRP. To avoid futile general anesthesia, a policy should be enforced to ensure
      that the da Vinci system is completely set up before the patient enters the
      operating room.

PMID- 18042028
TI  - External validation of a nomogram for prediction of side-specific extracapsular
      extension at robotic radical prostatectomy.
AB  - BACKGROUND AND PURPOSE: Several staging tools have been developed for open
      radical prostatectomy (ORP) patients. However, the validity of these tools has
      never been formally tested in patients treated with robot-assisted laparoscopic
      radical prostatectomy (RALP). We tested the accuracy of an ORP-derived nomogram
      in predicting the rate of extracapsular extension (ECE) in a large RALP cohort.
      PATIENTS AND METHODS: Serum prostate specific antigen (PSA) and side-specific
      clinical stage and biopsy Gleason sum information were used in a previously
      validated nomogram predicting side-specific ECE. The nomogram-derived predictions
      were compared with the observed rate of ECE, and the accuracy of the predictions
      was quantified. Each prostate lobe was analyzed independently. As complete data
      were available for 576 patients, the analyses targeted 1152 prostate lobes.
      Median age and serum PSA concentration at radical prostatectomy were 60 years and
      5.4 ng/mL, respectively. RESULTS: The majority of side-specific clinical stages
      were T(1c) (993; 86.2%). Most side-specific biopsy Gleason sums were 6 (572;
      49.7%). The median side-specific percentages of positive cores and of cancer
      were, respectively, 20.0% and 5.0%. At final pathologic review, 107 patients
      (18.6%) had ECE, and side-specific ECE was present in 117 patients (20.3%). The
      nomogram was 89% accurate in the RALP cohort v 84% in the previously reported ORP
      validation. CONCLUSIONS: The ORP side-specific ECE nomogram is highly accurate in
      the RALP population, suggesting that predictive and possibly prognostic tools
      developed in ORP patients may be equally accurate in their RALP counterparts.

PMID- 18042029
TI  - Is there a proper pelvic size for an extraperitoneal robot-assisted radical
      prostatectomy?
AB  - BACKGROUND: A narrow pelvis can potentially complicate an extraperitoneal radical
      robot-assisted prostatectomy (RAP). We report our experience with RAP and
      evaluate whether a narrow pelvis can affect treatment outcomes after
      extraperitoneal RAP. MATERIALS AND METHODS: We prospectively evaluated 50
      patients who underwent RAP during a 2-month period using the extraperitoneal
      approach. To approximate the relative size of the field available for working
      using the extraperitoneal approach, the arc length between the anterior superior
      iliac spines was estimated with the umbilicus as the center of the circle.
      Patients with an arc length measuring <33 cm were compared with those with an arc
      length > or =33 cm. Additional parameters evaluated included age, total operating
      time, estimated blood loss, prostate-specific antigen (PSA) level, pathological
      stage and Gleason grade, intraoperative and perioperative complications, surgical
      margin status, and continence at 3 months. RESULTS: Twenty-eight (56%) patients
      had an arc length <33 cm and twenty-two (44%) patients had an arc length > or =33
      cm. When comparing the two groups, no statistically significant difference (P >
      0.05) was noted in age, PSA level, blood loss (161 v 163 mL), operative time (174
      v 176 min), and total positive margin rates (14% v 13.6%). The continence rate at
      3 months was 66.6% and equal for both groups. CONCLUSION: In our experience, a
      narrow pelvis did not significantly affect operative outcome in patients
      undergoing an extraperitoneal radical RAP. Although this variable should be taken
      into account, it should not be a primary factor in deciding the route of access.

PMID- 18042030
TI  - Transurethral injection therapy with dextranomer/hyaluronic acid copolymer
      (Deflux) for treatment of secondary vesicoureteral reflux after renal
      transplantation.
AB  - BACKGROUND AND PURPOSE: Secondary vesicoureteral reflux (SVUR) after renal
      transplantation may cause recurrent urinary-tract infections (UTI) and loss of
      renal function. There are only a few reports on the endoscopic treatment of SVUR
      by transurethral injection therapy. This is the first report of transurethral
      injection of dextranomer/hyaluronic acid copolymer (Deflux; Q-Med Scandinavia,
      Uppsala, Sweden) to relieve SVUR after renal transplantation. PATIENTS AND
      METHODS: Between November 2003 and October 2005, four women were treated for SVUR
      with transurethral injections of dextranomer/hyaluronic acid copolymer. All
      patients had deterioration of renal function attributable to SVUR, recurrent UTI,
      or both. The mean follow-up was 29 months (range 16-38 months). RESULTS:
      Initially, SVUR was corrected in all patients. Recurrent SVUR made a second
      treatment necessary in two patients. Three patients had no signs of SVUR 15, 27,
      and 36 months after the treatment. Renal function remained stable in these
      patients, and two were free of UTI. One of the patients who received two Deflux
      injections developed a filiform stenosis of the distal ureter, which was
      corrected by ureteropyeloplasty with the native ureter. CONCLUSION: Transurethral
      injection therapy with Deflux is a minimally invasive treatment option for
      patients with SVUR after renal transplantation. A second treatment seems to be
      necessary in some cases. Complications such as ureteral obstruction may occur.

PMID- 18042031
TI  - Characterizing TUNA ablative treatments of the prostate for benign hyperplasia
      with gadolinium-enhanced magnetic resonance imaging.
AB  - BACKGROUND AND PURPOSE: Transurethral Needle Ablation of the prostate TUNA has
      been accepted as an office-based treatment for benign prostatic hyperplasia (BPH)
      for many years. Clinical outcomes have been reported, but the amount and location
      of the necrosis produced have yet to be characterized. The necrosis caused by
      TUNA was evaluated by gadolinium-enhanced magnetic resonance imaging (MRI) of the
      pelvis. PATIENTS AND METHODS: Twelve patients with BPH/lower urinary-tract
      symptoms underwent standard TUNA, and MRI scans with gadolinium enhancement were
      performed before and 1 week after treatment. The images were studied using
      Analyze software to quantify the amount of necrosis compared with the prostatic
      volume. Transverse, coronal, and sagittal images were obtained to identify the
      location of the necrosis. RESULTS: New gadolinium defects were seen in all
      patients after TUNA. The lesions coalesced into continuous areas of necrosis and
      correlated with the site of needle placement. The mean volume of necrosis was
      6.84 cc and equated to 8.6% of the prostate volume. No lesions were found near
      the apex, urethra, or rectum; and none extended beyond the prostate capsule.
      CONCLUSIONS: Gadolinium-enhanced MRI demonstrates new vascular defects
      representing necrosis caused by TUNA of the prostate. This therapy for BPH
      produces necrotic lesions that can be placed strategically by the surgeon. The
      standard protocol produces lesions that coalesce to create larger lesions. This
      MRI study has characterized, for the first time, the heating pattern and
      intraprostatic necrosis of a complete TUNA procedure.

PMID- 18042032
TI  - Pain scores and local anesthesia for transrectal ultrasound-guided prostate
      biopsy in patients with anorectal pathologies.
AB  - PURPOSE: The aim of the present randomized study was to evaluate the efficacy of
      lidocaine gel compared with dimethylsulfoxide (DMSO) with lidocaine for
      transrectal ultrasonography (TRUS)-guided prostate biopsy in patients with
      anorectal pathologies. PATIENTS AND METHODS: Sixty-two patients were randomly
      divided into two equal groups. Group 1 was given 10 mL of 2% lidocaine gel
      intrarectally 10 minutes before the biopsy. Group 2 was given 10 mL of
      intrarectal 40% DMSO with an amount of lidocaine equal to that in the lidocaine
      gel 10 minutes before the procedure. The degree of pain was rated by patients
      using a 10-point visual analog scale. RESULTS: The pain scores for probe
      insertion were significantly lower for group 2 (3.15 +/- 1.41) than for group 1
      (4.58 +/- 160) (P = 0.01). No significant differences were found between the pain
      scores of the two groups for biopsy-needle insertion (P = 0.62). CONCLUSIONS:
      Dimethylsulfoxide with lidocaine instilled into the rectum is a simple, safe,
      rapid-acting, and effective method of anesthesia delivery before TRUS-guided
      prostate biopsy in patients with anorectal pathologies.

PMID- 18042033
TI  - Urinary leakage after laparoscopic radical prostatectomy: a systematic review.
AB  - PURPOSE: To review the literature on the definition and incidence of leakage
      after laparoscopic radical prostatectomy (LRP) as well as its relation to the
      surgeon's technical experience, the type of urethrovesical suture, and the
      approach (extraperitoneal or transperitoneal). MATERIALS AND METHODS: We
      conducted a systematic review of the subject, consulting MEDLINE, Embase, and
      Cochrane library (MeSH terms "radical prostatectomy," "laparoscopy," "anastomotic
      leakage," and "complications"). Languages were limited to English, Spanish, and
      French. Selection criteria were original papers with 30 or more patients and
      description of the leakage rate. Data on mean catheterization days, surgical
      approach, and type of suture were retrieved. Papers were included after approval
      by two independent reviewers. Statistical analysis was performed with SPSS V. 12.
      A P value <0.05 was considered significant. RESULTS: A total of 24 articles were
      identified meeting the inclusion criteria. Most of them were observational. There
      were no randomized controlled trials. Meta-analysis was not performed because of
      clinical heterogeneity. Leakage was defined in 11 of the papers, and great
      variation in the definition was found. On average, the incidence of anastomotic
      leakage was 9.7% (396/4091 patients) and ranged from 3.2% to 33%. None of the
      risk factors studied showed statistical significance, although some individual
      series demonstrated a decrease in the leakage rate with increasing surgeon
      experience. CONCLUSIONS: The evidence in the studies on urine leakage after LRP
      is poor. There is a lack of a uniform definition of the condition. Time frame,
      diagnostic method, and significance need to be standardized. This lack of
      definition, together with the character of the studies and the heterogeneity of
      the series, makes comparison difficult, precluding a proper meta-analysis.

PMID- 18042034
TI  - New model for training in laparoscopic dismembered ureteropyeloplasty.
AB  - PURPOSE: To create an animal model for teaching laparoscopic dismembered
      pyeloplasty in which a realistic anatomic environment and the technical points of
      the procedure could be duplicated. MATERIALS AND METHODS: Ten pigs underwent
      general anesthesia, and the ureter was dissected and spatulated. The small
      intestine near the renal hilum was trimmed to replace the enlarged renal pelvis,
      and the "ureteropelvic" anastomosis was performed according to the standard
      operation steps. A double-pigtail stent was placed in the ureter in antegrade
      fashion. This model was used by trainees during their year of fellowship in
      advanced laparoscopic urology. A mentor-trainee fellowship program was planned to
      guarantee the success of the operations and the quality of the anastomoses. The
      learning curve was analyzed in terms of the time necessary to perform the task.
      RESULTS: This model reproduced the technical complexity of laparoscopic
      dismembered pyeloplasty. The total operating time declined from 135 +/- 14.6
      minutes (range 121-155 minutes) to 62 +/- 5.2 minutes (range 56-70 minutes) after
      the trainees had performed 12 pyeloplasties. The time needed for intraoperative
      antegrade stenting declined from 35 +/- 12 minutes to 8 +/- 2 minutes. Six
      pyeloplasties could be performed in every pig with adequate substitutes for an
      enlarged renal pelvis. With this training, all participants were able to perform
      ureteropelvic anastomosis and intraoperative antegrade stenting skillfully.
      CONCLUSION: This model not only allows trainees to acquire the skills necessary
      for laparoscopic dismembered pyeloplasty but also provides more practices with
      the use of a suitable renal pelvic substitute.

PMID- 18042035
TI  - Interstitial laser ablation of the kidney: acute and chronic porcine study using
      new-generation diffuser tip fiber.
AB  - BACKGROUND AND PURPOSE: Many ablative techniques have been described for
      treatment of small renal tumors. We investigated interstitial laser ablation
      (ILA) of porcine kidneys with a new-generation diffuser tip fiber. MATERIALS AND
      METHODS: Six female farm pigs underwent bilateral lower-pole ILA of normal
      kidneys via a midline approach. The acute group consisted of three pigs that
      underwent immediate post-treatment bilateral nephrectomy, while the chronic group
      survived for 45 days prior to bilateral nephrectomy. The lower pole of each
      kidney was treated with a diode laser in temperature-adaptive mode (100 degrees
      C) with the diffuser tip fiber. The treatment time was increased for each pig in
      each group, from 4 minutes to 8 minutes to 12 minutes. RESULTS: The acute lesions
      were elliptical, with the depth being longer than the width. The dimensions of
      the acute lesions on gross inspection were 18 x 9 and 17 x 9 mm in the 4-minute
      treatment pig, 25 x 6 and 18 x 15 mm in the 8-minute treatment pig, and 22 x 18
      and 19 x 12-mm in the 12-minute treatment pig. Reduced nicotinamide adenine
      dinucleotide staining of the acute lesions revealed a nonviable zone of 14 x 18
      and 15 x 10 mm in the 4-minute treatment pig, 16 x 8 and 12 x 7 mm in the 8
      minute treatment pig, and 11 x 7 and 14 x 9 mm in the 12-minute treatment pig.
      Histologic architecture was preserved. Gross examination of the chronic kidney
      revealed a divot with a scar in the treatment area. Histologic examination showed
      an irregularly shaped area of fibrosis and loss of normal architecture, with the
      lesions being smaller than those seen on the acute sections. CONCLUSIONS:
      Interstitial laser ablation of the kidney with a diffuser tip fiber produces
      adequate cell death but small lesions. Further studies with multiple fibers or
      active monitoring and repositioning of the fiber to produce larger lesions are
      necessary.

PMID- 18042039
TI  - Identification of small molecules from human embryonic stem cells using
      metabolomics.
AB  - Metabolomics enables the discovery of small molecules that may serve as candidate
      biomarkers of pharmacological efficacy or toxicity. Biochemical pathways of human
      development are likely active in human embryonic stem (hES) cells and
      derivatives, since they recapitulate organogenesis in vitro. We hypothesized that
      small molecules could be measured from undifferentiated hES cells and hES cell
      derived neural precursors (hNPs) using metabolomics and that these compounds are
      altered in response to known disruptors of human development. Metabolite
      profiling was performed in hES cells and hNPs after exposure to valproate, an
      inducer of neurodevelopmental disorders. Kynurenine, an intermediate in
      tryptophan metabolism, and other small molecules in glutamate metabolism were
      significantly upregulated in response to valproate. Thus, for the first time, we
      have been able to measure and identify small molecules secreted from hES cells
      and cells derived from hES cells. The hES cell metabolome may thus serve as a
      source of candidate biomarkers to predict or measure pharmacological efficacy or
      toxic response.

PMID- 18042040
TI  - Hepcidin expression in mouse retina and its regulation via
      lipopolysaccharide/Toll-like receptor-4 pathway independent of Hfe.
AB  - Hepcidin is a hormone central to the regulation of iron homeostasis in the body.
      It is believed to be produced exclusively by the liver. Ferroportin, an iron
      exporter, is the receptor for hepcidin. This transporter/receptor is expressed in
      Muller cells, photoreceptor cells and the RPE (retinal pigment epithelium) within
      the retina. Since the retina is protected by the retinal-blood barriers, we asked
      whether ferroportin in the retina is regulated by hepcidin in the circulation or
      whether the retina produces hepcidin for regulation of its own iron homeostasis.
      Here we show that hepcidin is expressed robustly in Muller cells, photoreceptor
      cells and RPE cells, closely resembling the expression pattern of ferroportin. We
      also show that bacterial LPS (lipopolysaccharide) is a regulator of hepcidin
      expression in Muller cells and the RPE, both in vitro and in vivo, and that the
      regulation occurs at the transcriptional level. The action of LPS on hepcidin
      expression is mediated by the TLR4 (Toll-like receptor-4). The upregulation of
      hepcidin by LPS occurs independent of Hfe (human leukocyte antigen-like protein
      involved in Fe homeostasis). The increase in hepcidin levels in retinal cells in
      response to LPS treatment is associated with a decrease in ferroportin levels.
      The LPS-induced upregulation of hepcidin and consequent down-regulation of
      ferroportin is associated with increased oxidative stress and apoptosis within
      the retina in vivo. We conclude that retinal iron homeostasis may be regulated in
      an autonomous manner by hepcidin generated within the retina and that chronic
      bacterial infection/inflammation of the retina may disrupt iron homeostasis and
      retinal function.

PMID- 18042041
TI  - Dentin non-collagenous proteins (dNCPs) can stimulate dental follicle cells to
      differentiate into cementoblast lineages.
AB  - BACKGROUND INFORMATION: Although the mechanism of cementogenesis is an area full
      of debate, the DFCs (dental follicle cells) are thought to be the precursors of
      cementoblasts. At the onset of cementogenesis, DFCs come into contact with the
      root dentin surface and undergo subsequent differentiation. But the exact effects
      of dentin or dentin matrix on DFCs remain an open question. In the present study,
      we hypothesized that dNCPs (dentin non-collagenous proteins) extracted from
      dentin could stimulate DFCs to differentiate into cementoblast lineages. RESULTS:
      DFCs were isolated from tooth germs of SD (Sprague-Dawley) rats and then co
      cultured with dNCPs. Treated DFCs presented several features of cementoblast
      lineages in vitro, as indicated by morphological changes, decreased
      proliferation, enhanced ALP (alkaline phosphatase) activity and increased matrix
      mineralization. The expression of mineralization-associated proteins and genes
      were up-regulated after induction, whereas the expression of specific markers of
      odontoblast were not detected. Incubation of treated DFC pellets in vivo revealed
      that a large amount of cementum-like tissues was formed within the novel dentin
      carriers, which were quite distinct from the newly formed osteodentin secreted by
      DPSCs (dental pulp stem cells). The negative expression of DSP (dentin
      sialoprotein) also excluded the possibility of producing dentin matrix by treated
      DFCs. CONCLUSIONS: dNCPs can stimulate DFCs to differentiate into cementoblast
      lineages. The present study provides new insights into the mechanism of
      cementogenesis.

PMID- 18042042
TI  - APC nuclear membrane association and microtubule polarity.
AB  - BACKGROUND INFORMATION: Directional cell migration is a fundamental feature of
      embryonic development, the inflammatory response and the metastatic spread of
      cancer. Migrating cells have a polarized morphology with an asymmetric
      distribution of signalling molecules and of the actin and microtubule
      cytoskeletons. The dynamic reorganization of the actin cytoskeleton provides the
      major driving force for migration in all mammalian cell types, but microtubules
      also play an important role in many cells, most notably neuronal precursors.
      RESULTS: We previously showed, using primary fibroblasts and astrocytes in in
      vitro scratch-induced migration assays, that the accumulation of APC (adenomatous
      polyposis coli; the APC tumour suppressor protein) at microtubule plus-ends
      promotes their association with the plasma membrane at the leading edge. This is
      required for polarization of the microtubule cytoskeleton during directional
      migration. Here, we have examined the organization of microtubules in the soma of
      migrating neurons and fibroblasts. CONCLUSIONS: We find that APC, through a
      direct interaction with the NPC (nuclear pore complex) protein Nup153
      (nucleoporin 153), promotes the association of microtubules with the nuclear
      membrane.

PMID- 18042043
TI  - Identification and characterization of the Arabidopsis gene encoding the
      tetrapyrrole biosynthesis enzyme uroporphyrinogen III synthase.
AB  - UROS (uroporphyrinogen III synthase; EC 4.2.1.75) is the enzyme responsible for
      the formation of uroporphyrinogen III, the precursor of all cellular
      tetrapyrroles including haem, chlorophyll and bilins. Although UROS genes have
      been cloned from many organisms, the level of sequence conservation between them
      is low, making sequence similarity searches difficult. As an alternative approach
      to identify the UROS gene from plants, we used functional complementation, since
      this does not require conservation of primary sequence. A mutant of Saccharomyces
      cerevisiae was constructed in which the HEM4 gene encoding UROS was deleted. This
      mutant was transformed with an Arabidopsis thaliana cDNA library in a yeast
      expression vector and two colonies were obtained that could grow in the absence
      of haem. The rescuing plasmids encoded an ORF (open reading frame) of 321 amino
      acids which, when subcloned into an Escherichia coli expression vector, was able
      to complement an E. coli hemD mutant defective in UROS. Final proof that the ORF
      encoded UROS came from the fact that the recombinant protein expressed with an N
      terminal histidine-tag was found to have UROS activity. Comparison of the
      sequence of AtUROS (A. thaliana UROS) with the human enzyme found that the seven
      invariant residues previously identified were conserved, including three shown to
      be important for enzyme activity. Furthermore, a structure-based homology search
      of the protein database with AtUROS identified the human crystal structure.
      AtUROS has an N-terminal extension compared with orthologues from other
      organisms, suggesting that this might act as a targeting sequence. The precursor
      protein of 34 kDa translated in vitro was imported into isolated chloroplasts and
      processed to the mature size of 29 kDa. Confocal microscopy of plant cells
      transiently expressing a fusion protein of AtUROS with GFP (green fluorescent
      protein) confirmed that AtUROS was targeted exclusively to chloroplasts in vivo.

PMID- 18042044
TI  - Two different classes of E2 ubiquitin-conjugating enzymes are required for the
      mono-ubiquitination of proteins and elongation by polyubiquitin chains with a
      specific topology.
AB  - RING (really interesting new gene) and U-box E3 ligases bridge E2 ubiquitin
      conjugating enzymes and substrates to enable the transfer of ubiquitin to a
      lysine residue on the substrate or to one of the seven lysine residues of
      ubiquitin for polyubiquitin chain elongation. Different polyubiquitin chains have
      different functions. Lys(48)-linked chains target proteins for proteasomal
      degradation, and Lys(63)-linked chains function in signal transduction,
      endocytosis and DNA repair. For this reason, chain topology must be tightly
      controlled. Using the U-box E3 ligase CHIP [C-terminus of the Hsc (heat-shock
      cognate) 70-interacting protein] and the RING E3 ligase TRAF6 (tumour-necrosis
      factor-receptor-associated factor 6) with the E2s Ubc13 (ubiquitin-conjugating
      enzyme 13)-Uev1a (ubiquitin E2 variant 1a) and UbcH5a, in the present study we
      demonstrate that Ubc13-Uev1a supports the formation of free Lys(63)-linked
      polyubiquitin chains not attached to CHIP or TRAF6, whereas UbcH5a catalyses the
      formation of polyubiquitin chains linked to CHIP and TRAF6 that lack specificity
      for any lysine residue of ubiquitin. Therefore the abilities of these E2s to
      ubiquitinate a substrate and to elongate polyubiquitin chains of a specific
      topology appear to be mutually exclusive. Thus two different classes of E2 may be
      required to attach a polyubiquitin chain of a particular topology to a substrate:
      the properties of one E2 are designed to mono-ubiquitinate a substrate with no or
      little inherent specificity for an acceptor lysine residue, whereas the
      properties of the second E2 are tailored to the elongation of a polyubiquitin
      chain using a defined lysine residue of ubiquitin.

PMID- 18042045
TI  - Brm transactivates the telomerase reverse transcriptase (TERT) gene and modulates
      the splicing patterns of its transcripts in concert with p54(nrb).
AB  - We report that a DBHS (Drosophila behaviour, human splicing) family protein,
      p54(nrb), binds both BRG1 (Brahma-related gene 1) and Brm (Brahma), catalytic
      subunits of the SWI/SNF (switch/sucrose non-fermentable) chromatin remodelling
      complex, and also another core subunit of this complex, BAF60a. The N-terminal
      region of p54(nrb) is sufficient to pull-down other core subunits of the SWI/SNF
      complex, suggesting that p54(nrb) binds SWI/SNF-like complexes. PSF
      (polypyrimidine tract-binding protein-associated splicing factor), another DBHS
      family protein known to directly bind p54(nrb), was also found to associate with
      the SWI/SNF-like complex. When sh (short hairpin) RNAs targeting Brm were
      retrovirally expressed in a BRG1-deficient human cell line (NCI-H1299), the
      resulting clones showed down-regulation of the TERT (telomerase reverse
      transcriptase) gene and an enhancement of ratios of exon-7-and-8-excluded TERT
      mRNA that encodes a beta-site-deleted inactive protein. All of these clones
      display growth arrest within 2 months of the Brm-knockdown. In NCI-H1299 cells,
      Brm, p54(nrb), PSF and RNA polymerase II phosphorylated on CTD (C-terminal
      domain) Ser(2) specifically co-localize at a region incorporating an alternative
      splicing acceptor site of TERT exon 7. These findings suggest that, at the TERT
      gene locus in human tumour cells containing a functional SWI/SNF complex, Brm,
      and possibly BRG1, in concert with p54(nrb), would initiate efficient
      transcription and could be involved in the subsequent splicing of TERT
      transcripts by accelerating exon-inclusion, which partly contributes to the
      maintenance of active telomerase.

PMID- 18042046
TI  - Extracranial vertebral artery intervention.
AB  - Atherosclerosis is the commonest cause of vertebral artery stenosis and has a
      predilection for the origin and proximal section of the extracranial portion of
      the vessel and also the intracranial portion of the vessel. Although it has
      generally been thought that extracranial vertebral artery (ECVA) disease has a
      more benign outcome compared to intracranial vertebral artery disease,
      significant occlusive disease of the proximal vertebral artery is the primary
      cause of vertebral artery ischemia in a significant proportion of patients. We
      focus on the interventional management of patients with proximal ECVA disease in
      this article.

PMID- 18042047
TI  - Peripheral atherectomy: a critical review.
AB  - Atherectomy is experiencing increased interest from endovascular specialists as a
      therapeutic treatment in the peripheral arteries. Long studied in the coronary
      vasculature, atherectomy has several theoretical advantages that make it uniquely
      suited for the peripheral circulation. In particular, infra-inguinal peripheral
      arterial disease experiences physiologic stresses and forces that have made
      traditional percutaneous coronary treatments such as angioplasty and stenting not
      as successful. Restenosis has been a major problem for angioplasty and stenting
      alone. The SilverHawk atherectomy device has favorable short-term data but
      important longer-term data are limited and need further study. Laser atherectomy
      also has favorable applications in niche patients but the number of studies is
      limited. Unfortunately, athero-ablative technologies for peripheral arterial
      disease require more definitive objective data regarding 12-month and longer-term
      outcomes in order to obtain widespread scientific acceptance.

PMID- 18042048
TI  - FDA advisory panel on the safety and efficacy of drug-eluting stents: summary of
      findings and recommendations.

PMID- 18042049
TI  - Importance of intensive lipid lowering in acute coronary syndrome and
      percutaneous coronary intervention.
AB  - Lipid-lowering therapy with statins reduces the risk of cardiovascular events in
      patients with established coronary heart disease (CHD). Traditionally, statins
      were perceived to lower the long-term cardiovascular risk by reducing elevated
      low-density lipoprotein cholesterol (LCL-C). Recently, this benefit has been
      established for patients early after acute coronary syndrome (ACS). The benefit
      appears linked to reductions in both LDL-C and C-reactive protein (CRP) that is a
      marker of systemic inflammation. This paper will review the current state of
      evidence from key recent statin trials in ACS and percutaneous coronary
      intervention (PCI) and discuss their significance for clinical practice.

PMID- 18042050
TI  - Long-term clinical benefit of sirolimus-eluting stents compared to bare metal
      stents in the treatment of saphenous vein graft disease.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of sirolimus
      eluting stents (SES) in the treatment of saphenous vein graft (SVG) disease.
      BACKGROUND: Percutaneous coronary intervention (PCI) of SVG lesions with bare
      metal stents (BMS) is associated with frequent in-stent restenosis, progression
      of disease in nonstented SVG segments, and suboptimal clinical outcomes. While
      SES have been shown to reduce restenosis rates in various native lesion subsets,
      the long-term clinical impact of SES use in SVG lesions is less clear. METHODS:
      We compared our first 59 patients who underwent SES implantation in SVGs with 50
      consecutive patients who received BMS in an equivalent time period prior to SES
      availability. Clinical outcomes were compared in both groups. RESULTS: Baseline
      clinical variables between the two groups were similar. Mean graft age in the SES
      cohort was older than that in the BMS cohort (12.9 years vs. 9.4 years). At
      follow-up, the SES group had a 24.6% absolute lower incidence of major adverse
      cardiac events (MACE) (25.4% vs. 50.0%), driven by a 20.7% absolute lower
      incidence of target vessel revascularization (TVR) (15.3% vs. 36.0%). The SES
      treatment group had a 24.1% lower rate of clinical restenosis (11.9% vs. 36.0%).
      The use of a SES was an independent negative predictor of MACE at a mean follow
      up of 20 months (odds ratio [OR]= 0.48,P = 0.03). CONCLUSIONS: Despite the
      placement of longer stents in patients with older, smaller SVGs, the use of SES
      in the treatment of SVG lesions appears to be safe and is associated with less
      clinical restenosis and more favorable long-term clinical outcomes as compared
      with BMS.

PMID- 18042051
TI  - The retrograde coronary approach for chronic total occlusions: mid-term results
      and technical tips & tricks.
AB  - BACKGROUND: Coronary chronic total occlusions (CTO) remain a challenging lesion
      subset for interventional cardiologists. The retrograde approach is a novel but
      still incompletely described technique. We report our 5-year-long experience in
      retrograde percutaneous coronary intervention (PCI) for CTOs. METHODS: We
      abstracted patient and procedural data on all cases with attempted retrograde
      approach by means of a native septal or epicardial collateral pathway. End-points
      were wiring, angiographic and procedural success, plus long-term major adverse
      cardiovascular events (MACE). RESULTS: The retrograde approach was used in 18
      patients, including 11 CTOs of right coronary artery (RCA), 3 of left circumflex
      (LCX), and 4 of left anterior descending (LAD), with procedural success in 12
      (67%). Conversely, two cases of wiring failures, three angiographic failures
      despite successful retrograde wiring, and one postprocedural myocardial
      infarction in an otherwise angiographically successful procedure were found.
      Causes of wiring failure were inability to retrogradely cross the distal (1) or
      the proximal stump (1) with the wire, while angiographic failures were due to
      interruption of the procedure due to rupture of a minor septal collateral branch
      during attempts at advancing the noninflated balloon (1) or persistent inability
      to deliver the balloon through the chosen collateral (2). Follow-up at a mean of
      15 months showed MACE had occurred in five (28%) subjects. CONCLUSIONS: The
      retrograde approach appears feasible and safe in the percutaneous management of
      coronary occlusions, and its application can be envisioned as a promising
      alternative in selected patients in whom antegrade approaches fail or are unsafe.

PMID- 18042052
TI  - Distal embolization during native vessel and vein graft coronary intervention
      with a vascular protection device: predictors of high-risk lesions.
AB  - OBJECTIVE: We sought to define clinical and angiographic variables that may
      predict patients and lesions at increased risk for distal embolism during
      percutaneous intervention (PCI), as assessed by debris retrieval from a distal
      protection filter device. BACKGROUND: Distal thrombo- and atheroembolism may
      contribute to periprocedural myocardial necrosis during PCI, which may in turn
      affect long-term outcomes. Distal protection devices have been used to reduce
      this occurrence with variable outcomes depending on lesion and patient subsets.
      METHODS: 194 consecutive patients in whom the FilterWire(R) device (FW) [Boston
      Scientific Corp., Natick, MA] was used for native coronary vessel (n =129) or
      vein graft (n = 65) PCI were studied. FW debris was visually analyzed using a
      semi-quantitative grading score. Patients with "significant" debris (particles >
      or = 1 mm diameter) were compared with those with "nonsignificant" debris (no
      debris or particles <1 mm) with respect to clinical (age, gender, coronary
      disease risk factors, clinical presentation, periprocedural medications), and
      angiographic (vessel treated, vessel size, lesion length, lesion characteristics,
      angiographic thrombus and TIMI flow before and after PCI) variables. RESULTS:
      Significant debris was retrieved in 55% of patients, more frequently from vein
      graft (69%) than native vessel lesions (48%, p = 0.006). No clinical
      characteristics predicted significant debris retrieval. Angiographic predictors
      of significant debris by multivariate analysis were longer stent length and final
      TIMI flow <3 (p = 0.009 and 0.007, respectively). CONCLUSION: Longer stent
      length, likely reflecting increased lesion length and plaque burden, predicted
      significant distal embolism during PCI in native vessel and vein graft lesions,
      as assessed by debris collected in a distal vascular protection device. This
      suggests that use of vascular protection devices should be considered during PCI
      of long lesions.

PMID- 18042053
TI  - Improvement in endothelium dysfunction in diabetics treated with statins: a
      randomized comparison of atorvastatin 20 mg versus rosuvastatin 10 mg.
AB  - AIM: To investigate the effect a 3-month treatment with atorvastatin 20 mg
      compared with rosuvastatin 10 mg on endothelium dysfunction in subjects with
      diabetes. METHODS: A total of 22 consecutive subjects with diabetes who were not
      receiving statins were enrolled in the study. Endothelium function was assessed
      before treatment (T0), after 1 month (T1), and after 3 months of treatment (T2)
      with statins with brachial echo-Doppler test. Patients were randomized to receive
      atorvastatin 20 mg or rosuvastatin 10 mg. Blood samples were drawn in the
      meantime in order to evaluate C-reactive protein (CRP) plasmatic concentrations.
      RESULTS: A total of 82% of patients enrolled showed endothelium dysfunction
      (hyperemic reserve <5%). Treatment with statins significantly improved
      endothelium function in diabetics. Subjects with endothelium dysfunction
      decreased from 82% (T0) to 44% (T2): mean hyperemic reserve values increased from
      2.64% (T0) to 3.23% (T1) and 4% (T2) in patients treated with rosuvastatin (ANOVA
      P < 0.01), and from 2.74% (T0) to 2.75% (T1) and 4.40% (T2) in those treated with
      atorvastatin (ANOVA P < 0.01); differences were significant only comparing T2
      with T0. Relative increase in endothelium reserve was 51.51% with rosuvastatin
      versus 60.58% with atorvastatin (P N.S.). Both statins significantly reduced
      plasmatic levels of CRP (3.18 +/- 2.43 mg/dL [T0] vs. 1.31 +/- 1.67 mg/dL [T2]
      with rosuvastatin [P < 0.01], 7.53 +/- 7.46 mg/dL [T0] vs. 2.92 +/- 2.06 mg/dL
      [T2] with atorvastatin [P < 0.01]). Relative reduction of CRP levels was -50.57%
      with rosuvastatin versus -36.28% with atorvastatin (P N.S.). CONCLUSION: A 3
      month treatment with either atorvastatin 20 mg or rosuvastatin 10 mg is effective
      in improving endothelium dysfunction in subjects with diabetes.

PMID- 18042054
TI  - Percutaneous mitral valve repair.

PMID- 18042055
TI  - Transcatheter mitral valve repair for functional mitral regurgitation: coronary
      sinus approach.
AB  - Mitral regurgitation has become recognized as an important health problem. More
      specifically, functional mitral regurgitation is associated with worse outcomes
      in heart failure, postmyocardial infarction, and perioperative coronary artery
      bypass surgery patients. Many patients with severe mitral regurgitation are
      denied or refused mitral valve surgery. A less invasive procedure with possibly
      fewer potential complications may thus be attractive for patients with severe
      mitral regurgitation. Devices used for coronary sinus (CS) mitral annuloplasty
      are directed toward patients with functional mitral regurgitation. Because of its
      easy accessibility and close relationship to the posterior mitral annulus (MA),
      alterations of the CS geometry with percutaneous devices may translate to
      displacement of the posterior annulus and correct mitral leaflet coaptation. This
      review will focus on the contemporary CS annuloplasty devices: (1) Edwards MONARC
      system; (2) Cardiac Dimensions CARILLON; and (3) Viacor Shape Changing Rods
      system. In addition, important information obtained from recent imaging studies
      describing the relationship between the CS, MA, and coronary arteries will be
      reviewed.

PMID- 18042057
TI  - ASD/PFO devices: what is in the pipeline?
AB  - Since the initial description of an atrial septal defect (ASD) occluding device
      in the mid-1970s by King and Mills, a number of devices have been developed. To
      date, various transcatheter devices and methods to close congenital heart defects
      are currently available commercially or within clinical trials. Devices have been
      designed specifically for the ASD and patent foramen ovale (PFO). The trend in
      interventional treatment of intracardiac shunts is toward defect-specific systems
      and new devices minimizing the foreign material left in the atria. This review
      first focuses on new devices that are not approved in the United States but are
      elsewhere, and then reviews the experimental devices for PFO and ASD closure.

PMID- 18042056
TI  - Aortic stenosis: assessment of the patient at risk.
AB  - The true incidence of aortic stenosis among the general population is unknown but
      aortic sclerosis, its precursor, has been estimated to affect about 25% of people
      over age 65, while an estimated 3% of the population over age 75 have severe
      aortic stenosis. Severe aortic stenosis, when accompanied by symptoms of angina,
      syncope, or heart failure, is associated with high mortality rates. Two
      dimensional and Doppler echocardiography are cornerstone tools for the evaluation
      and monitoring of aortic stenosis. Echocardiography helps identify the patient at
      risk of death and guide timing of aortic valve replacement. Other important
      diagnostic tools include cardiac catheterization, treadmill stress testing, and
      dobutamine stress echocardiography, although their use is limited to specific
      patient populations. Aortic valve replacement carries a significant operative
      risk of approximately 4.0%. However, risk of operative mortality varies according
      to comorbidities and disease presentation. There are many risk models that guide
      estimation of the risk of operative mortality. Understanding operative risk is
      important in patient care and the selection of patients for aortic valve
      replacement.

PMID- 18042058
TI  - Transcatheter closure of intracardiac defects in adults.
AB  - There has been a dramatic increase in the adult congenital heart disease
      population and appreciation of intracardiac shunt lesions discovered or acquired
      in adults over the past several years. Fortunately, this increase has been met
      with advances in imaging modalities, which permit a more accurate noninvasive
      assessment of cardiac defects. Additionally, the evolutions in both device
      technology as well as fluoroscopic and echocardiographic image guidance have
      permitted the safe and effective catheter-based closure of numerous intracardiac
      defects. With catheter-based closure procedures now considered the treatment of
      choice in most cases of intracardiac defect repair in adults, it is imperative
      that clinicians possess a sound understanding of intracardiac shunt lesions and
      indications for repair or closure so that they may better care for this unique
      subset of adult patients. This review will focus on the anatomy, pathophysiology,
      and current transcatheter therapeutic options for adult patients with patent
      foramen ovale (PFO), atrial septal defects (ASD), and ventricular septal defects
      (VSD).

PMID- 18042059
TI  - Finite element analysis of stent deployment: understanding stent fracture in
      percutaneous pulmonary valve implantation.
AB  - OBJECTIVES: To analyze factors responsible for stent fracture in percutaneous
      pulmonary valve implantation (PPVI) by finite element method. BACKGROUND: PPVI is
      an interventional catheter-based technique for treating significant pulmonary
      valve disease. Stent fracture is a recognized complication. METHODS: Three
      different stent models were created: (1) platinum-10% iridium alloy stent -
      resembles the first-generation PPVI device; (2) same geometry, but with the
      addition of gold over the strut intersections - models the current stent; (3)
      same design as 1, but made of thinner wire. For Model 3, a stent-in-stent
      solution was applied. Numerical analyses of the deployment of these devices were
      performed to understand the stress distribution and hence stent fracture
      potential. RESULTS: Model 1: Highest stresses occurred at the strut
      intersections, suggesting that this location may be at highest risk of fracture.
      This concurs with the in vivo stent fracture data. Model 2: Numerical analyses
      indicate that the stresses are lower at the strut intersections, but
      redistributed to the end of the gold reinforcements. This suggests that fractures
      in this device may occur just distal to the gold. This is indeed the clinical
      experience. Model 3 was weakest at bolstering the implantation site; however,
      when two stents were coupled (stent-in-stent technique), better strength and
      lower stresses were seen compared with Model 1 alone. CONCLUSIONS: Using finite
      element analysis of known stents, we were able to accurately predict stent
      fractures in the clinical situation. Furthermore, we have demonstrated that a
      stent-in-stent technique results in better device performance, which suggests a
      novel clinical strategy.

PMID- 18042060
TI  - A hybrid surgical transcatheter strategy for treating severe para-right
      atrioventricular valvular regurgitation in a patient with left atrial isomerism.
AB  - Paravalvular leaks are a recognized complication of valve replacement surgery. We
      report a 47-year-old man with left atrial isomerism, interrupted left sided
      inferior caval vein with unilateral left sided superior caval vein, a common
      atrium, and anomalous pulmonary venous connection to the coronary sinus, who had
      recurrent severe para-right atrioventricular (AV) regurgitation with gross right
      heart failure following tricuspid valve (TCV) replacement. He underwent a hybrid
      surgery-transcatheter treatment strategy in the cardiac catheterization
      laboratory, which led to significant improvement in hemodynamics and symptoms.
      This to our knowledge is the first reported case of a minimally invasive approach
      to para-right sided AV valve regurgitation.

PMID- 18042061
TI  - Initial experience with alcohol septal ablation using a novel magnetic navigation
      system.
AB  - OBJECTIVES: We compared the use of magnetically assisted intervention (MAI) with
      conventional guidewire techniques to perform alcohol septal ablation (ASA) in
      patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND:
      Treatment of symptomatic patients with HOCM using ASA has been established as an
      effective therapy. However, in many cases cannulaton of the septal artery can be
      technically challenging. Recently, a magnetically directed guidewire system has
      been developed to assist in navigation in difficult percutaneous interventions.
      By directing the guidewire to the septal branch, this system has potential to
      shorten the procedure time and increase success and safety of ASA in patients
      with HOCM. METHODS: From October 2004 through October 2006, 44 consecutive
      patients underwent ASA using MAI with the Niobe system (Stereotaxis, Inc., St.
      Louis, MO). We compared these patients to 29 age- and gradient-matched cases
      using conventional techniques performed by an operator with >100 prior cases.
      RESULTS: All procedures were successful. Both the MAI and conventional groups had
      improved symptoms, exercise times, and reduced gradients compared with baseline.
      One dissection occurred in the conventional group. Although there were no
      aggregate differences in acute or 3-month clinical outcomes, the time required
      for guidewire cannulation of the septal branch decreased progressively with
      increasing experience (third tertile vs first tertile (3 [1.25-4.75 vs 10.5 [6
      17] minutes, P = 0.004) compared with the conventional group (6 [2-10.25]
      minutes, P = 0.075 vs third tertile), suggesting a learning curve for MAI.
      CONCLUSIONS: MAI has the potential to improve wiring time and outcomes of HOCM
      patients undergoing ASA.

PMID- 18042062
TI  - Bioabsorbable stents.

PMID- 18042065
TI  - KIT and PDGFRalpha mutational analyses of mixed cell-type gastrointestinal
      stromal tumours.
AB  - AIMS: To determine whether the epithelioid and spindle components of a mixed cell
      type gastrointestinal stromal tumour (GIST) show the same receptor tyrosine
      kinase mutation and, by inference, the same sensitivity to imatinib. METHODS AND
      RESULTS: Six mixed cell-type GISTs were identified from 108 gastric GISTs.
      Clinicopathological and immunohistochemical data of the six neoplasms were
      collated. For each neoplasm, DNA was extracted separately from the laser
      microdissected epithelioid and spindle components and non-neoplastic tissue and
      sequenced for KIT and platelet-derived growth factor receptor (PDGFR)alpha
      mutations. The epithelioid component often showed less CD117 and/or CD34
      immunoreactivity than the spindle component of the same mixed cell-type GIST.
      Four mixed cell-type GISTs showed somatic KIT mutations (deletions in exon 11 in
      three tumours and an insertion in exon 9 in one tumour) and one showed a somatic
      PDGFRalpha mutation (point mutation in exon 18); in each of the five cases, both
      epithelioid and spindle components showed identical mutations. CONCLUSIONS: The
      presence of the same receptor tyrosine kinase mutation in both components of a
      mixed cell-type GIST suggests that both components should be equally responsive
      to imatinib treatment, and that such mutation is an early key event in the
      pathogenesis of these neoplasms.

PMID- 18042066
TI  - Goblet cell carcinoid of the appendix: a specific type of carcinoma.
AB  - AIMS: Goblet cell carcinoid is a poorly understood tumour of the appendix. The
      aim of this study was to determine whether it should be regarded as a separate
      entity or as a variant of classical carcinoid. METHODS AND RESULTS: The
      immunohistochemical expression pattern of 21 markers and the mutation status of
      KRas codon 12 were determined in 16 goblet cell carcinoids and compared with 14
      classical carcinoids, 19 colonic adenocarcinomas and 10 appendiceal mucinous
      cystadeno (carcino)mas. The results were subjected to a stepwise linear
      discriminant analysis. Goblet cell carcinoids were significantly different from
      the control groups. The most important markers for discriminating between the
      groups were CEA (classical carcinoid versus all others), KRas mutation (present
      in all mucinous cystadeno (carcino)mas), beta-catenin (goblet cell carcinoid
      versus left sided colonic adenocarcinoma) and chromogranin (goblet cell carcinoid
      versus right sided colonic adenocarcinoma). Expression of Math1 and HD5 was
      similar in goblet cell carcinoid and colonic adenocarcinoma but absent in
      classical carcinoid. CONCLUSION: The results suggest that goblet cell carcinoids
      should be regarded as a separate entity. The formerly used term 'crypt cell
      carcinoma' may be more appropriate because it reflects the more aggressive
      clinical behaviour of these tumours as well as their greater similarity to
      adenocarcinomas rather than to carcinoids.

PMID- 18042067
TI  - Expression of c-FLIP is primarily detected in diffuse large B-cell lymphoma and
      Hodgkin's lymphoma and correlates with lack of caspase 8 activation.
AB  - AIMS: Inhibition of apoptosis is important in the pathogenesis of lymphomas. c
      FLIP, a regulator of caspase 8-mediated apoptosis, plays an important role in
      protecting normal B and T cells from apoptosis and possibly also in lymphomas.
      Because of contradictory reports about immunohistochemical detection of c-FLIP
      expression, the aim was to test the specificity of four antibodies in c-FLIP
      transfected cells and subsequently to investigate expression of c-FLIP in
      different types of lymphoma. METHODS AND RESULTS: Two of four antibodies were
      specific. In primary lymphomas c-FLIP expression was restricted to Hodgkin's
      lymphomas (> 90%) and diffuse large B-cell lymphomas (44%). Burkitt lymphomas and
      indolent B-cell lymphomas were negative in all cases. No expression was detected
      in primary T-cell lymphomas, although expression was observed in one relapsed
      ALK+ anaplastic large cell lymphoma. Expression of c-FLIP was inversely
      correlated with caspase 8 activation. CONCLUSIONS: c-FLIP is important in escape
      of B cells from apoptosis during normal follicle centre cell reaction and may
      thus be an important early event in the development of B-cell-derived lymphomas.
      Moreover, non-specific staining of frequently used antibodies might explain
      discrepancies in different reports of c-FLIP expression.

PMID- 18042068
TI  - Differential expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue
      inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer:
      implications for tumour progression.
AB  - AIMS: To investigate the expression of matrix metalloproteinase (MMP)-2, MMP-9,
      and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma
      skin cancer (NMSC) and to compare their expression between different tumour types
      and with clinicopathological factors. METHODS AND RESULTS: A study of 11 normal
      skin, 29 Bowen's disease (BD), 40 squamous cell carcinoma (SCC) and 38 basal cell
      carcinoma (BCC) samples for MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was
      carried out using immunohistochemistry and in situ hybridization. The expression
      of all metalloproteinases was greater in tumours than in normal skin. MMP-2 and
      MMP-9 expression was more extensive in the stroma of SCC than of BCC or BD. TIMP
      1 expression was greater in the stroma of BCC than of SCC or BD and TIMP-2
      expression was greater in the stroma of SCC than of BD. There was a correlation
      between increased metalloproteinase expression and depth of lesion (MMP-2 and
      TIMP-2), inflammation (MMP-2, MMP-9, TIMP-1 and TIMP-2) and microvessel density
      (MMP-2, MMP-9 and TIMP-2). CONCLUSIONS: MMP-2, MMP-9, TIMP-1 and TIMP-2 play an
      important role in the pathogenesis of non-melanoma skin cancer, but differ
      significantly in their expression levels between the tumour types examined. The
      immunoexpression of these proteins may be useful indicators of cutaneous cancer
      invasion and progression.

PMID- 18042069
TI  - Clear-cell dermal duct tumour: another distinctive, previously underrecognized
      cutaneous adnexal neoplasm.
AB  - AIMS: To describe 13 examples of clear cell dermal duct tumour, a neoplasm
      previously underrecognized in the literature. METHODS AND RESULTS: Thirteen
      examples of a neoplasm that we have named clear-cell dermal duct tumour were
      studied histopathologically and immunohistochemically. Histopathologically, all
      lesions consisted of mostly dermal neoplasms mainly composed of multiple solid
      aggregations of clear cells involving the dermis. Although the neoplasms were
      mostly solid, ductal structures were identified in all cases.
      Immunohistochemically, neoplastic cells were immunoreactive for MNF116 and
      AE1/AE3 cytokeratins, but not for CAM5.2 or cytokeratin 7. Epithelial membrane
      antigen, carcinoembryonic antigen and glial cystic disease fibrillary protein 15
      decorated the ductal structures, but neoplastic cells were negative. In contrast
      to some other clear cell neoplasms of the skin, which may be associated with
      diabetes mellitus, none of our cases of clear cell dermal duct tumour developed
      in a diabetic patient. CONCLUSIONS: We consider these neoplasms to be clear cell
      dermal duct tumours for the following reasons: (i) the neoplasms were mostly
      composed of multiple solid aggregations of epithelial clear cells; (ii)
      neoplastic aggregations mostly involved the dermis; (iii) in some cases,
      neoplastic aggregations of conventional poroid cells were intermingled with the
      aggregations of clear cells; (iv) ductal structures were identified within some
      neoplastic aggregations; (iv) small areas of necrosis en masse were seen in some
      neoplastic aggregations; and (v) the stroma of the neoplasm was scant.

PMID- 18042070
TI  - Immunohistochemical expression patterns of AP2alpha and AP2gamma in the
      developing fetal human breast.
AB  - AIMS: AP2alpha (TFAP2A) and AP2gamma (TFAP2G) transcription factors have been
      implicated in the control of proliferation, differentiation and apoptosis of
      normal breast epithelium and in breast cancer. The aim of this study was to
      provide a comprehensive analysis of the expression patterns of TFAP2A and TFAP2G
      in the developing fetal breast anlage with other relevant markers. METHODS AND
      RESULTS: Sixty fetal and one infant human breast specimens from 14 weeks of
      gestational age to 5 months old were examined. The primary breast
      outgrowth/nipple showed TFAP2A expression by the basal cells (week 14), followed
      later by cytokeratin (CK) 5 co-expression (week 17). Sprouting of the secondary
      outgrowths was characterized by HER-2+ invading cells. Preliminary ductal buds
      were lined by TFAP2G/HER-1-expressing myoepithelial precursors (week 19).
      Maturation of TFAP2A/CK18+ epithelia and TFAP2G/smooth muscle actin-positive
      myoepithelia proceeded in a distal-to-proximal manner beginning in the terminal
      end buds (week 22). CK5+ progenitor cells and CK5/TFAP2A or CK5/TFAP2G co
      expressing intermediary glandular or myoepithelial cells were found in the
      terminal end buds of neonatal fetal breast tissue. CONCLUSIONS: AP2 transcription
      factors may play decisive pacemaker roles in initiating and coordinating budding
      and branching processes during formation of the fetal breast anlage, possibly via
      modulation of an epidermal growth factor receptor.

PMID- 18042071
TI  - The expression of Wilms' tumour-1 and Ca125 in invasive micropapillary carcinoma
      of the breast.
AB  - AIM: Metastases from ovarian serous papillary carcinoma to the breast and primary
      invasive micropapillary carcinoma of the breast are histologically similar. The
      distinction is clinically important to ensure appropriate management. Wilms'
      tumour-1 (WT1) and Ca125 are frequently expressed in serous papillary carcinomas,
      and uncommonly in unselected mammary carcinomas. One previous study found Ca125
      expression in 69% of invasive micropapillary carcinomas. The aim was to assess
      the frequency of expression of WT1 and Ca125 in invasive micropapillary
      carcinoma. METHODS AND RESULTS: Twenty-five of 34 invasive micropapillary
      carcinomas showed no nuclear expression of WT1. The remaining nine tumours showed
      weak to moderate immunoreactivity in 1-10% of nuclei. Six of these nine tumours
      also contained ductal carcinoma in situ, which expressed WT1 in five of the six.
      Membranous or cytoplasmic expression of Ca125 was found in seven tumours.
      CONCLUSION: Nuclear WT1 expression is present in a minority of invasive
      micropapillary carcinomas and, when present, expression is focal. The frequency
      of expression of Ca125 was similar to the results in unselected mammary
      carcinoma. Thus, these markers are useful members of the immunohistochemical
      panel for the distinction of mammary invasive micropapillary carcinoma from
      ovarian serous papillary carcinoma.

PMID- 18042072
TI  - Evaluation of oestrogen receptor expression in breast cancer by quantification of
      mRNA.
AB  - AIMS: cDNA microarrays have subclassified breast carcinomas into molecular
      subtypes with oestrogen receptor-alpha (ER) gene expression as a main marker. The
      aim was to compare ER expression in 97 patients with operable breast cancer
      estimated by real-time reverse transcriptase-polymerase chain reaction (real-time
      RT-PCR) and by routine immunohistochemistry, and to determine which method was
      reliable for molecular subtyping in relation to basal-type keratins and HER2 gene
      expression. METHODS AND RESULTS: Frozen tumour samples were analysed by real-time
      RT-PCR for the expression of ER, HER2, keratin 5 and keratin 17 genes. In a group
      of 27 tumours with a low level of ER mRNA (<1.00), there were eight ER+ cases as
      assessed by immunohistochemistry, and of 70 cases with a high level of ER mRNA
      (>or=1.00), 26 were ER- by immunohistochemistry (P = 0.003). Lack of prognostic
      relevance of ER mRNA level was demonstrated, whereas assessment by
      immunohistochemistry was related to clinical outcome. Expression of basal
      keratins and HER2 genes differed significantly between ER+ and ER- tumours based
      on immunohistochemistry, but not on mRNA level. CONCLUSIONS: These results throw
      doubt on the assessment of ER mRNA as a key factor in the molecular distinction
      between breast tumours.

PMID- 18042073
TI  - Myofibroblasts in the stroma of oral squamous cell carcinoma are associated with
      poor prognosis.

PMID- 18042074
TI  - Expression of human herpesvirus 8 (HHV-8), latent nuclear antigen 1 (LANA1) in
      angiosarcoma in acquired immunodeficiency syndrome (AIDS) - a report of two
      cases.

PMID- 18042075
TI  - Malignancy in giant cell tumour of bone: is there a reproducible histological
      threshold? A study of three giant cell tumours with worrisome features.

PMID- 18042076
TI  - Hodgkin transformation of small lymphocytic lymphoma: gene usage, mutational
      status and clonal relationship.

PMID- 18042077
TI  - Maspin expression is up-regulated during the progression of endometrioid
      endometrial carcinoma.

PMID- 18042078
TI  - Diagnostic value of cytokeratin 7, CD10 and mesothelin in distinguishing ovarian
      clear cell carcinoma from metastasis of renal clear cell carcinoma.

PMID- 18042079
TI  - The impact of site and extent of clinically evident cardiovascular disease and
      atherosclerotic burden on new cardiovascular events in patients with Type 2
      diabetes. The SMART study.
AB  - AIMS: Patients with Type 2 diabetes and coronary heart disease (CHD) have an
      excess cardiovascular risk. The relationship of both other sites [cerebrovascular
      disease, peripheral arterial disease (PAD)] and the extent of clinically evident
      cardiovascular disease (CVD) with the occurrence of new cardiovascular events
      have not been investigated previously in patients with diabetes. We aimed to
      quantify this relationship and to assess the additional influence of
      atherosclerotic burden. METHODS: From 1996 to 2005, 776 patients with Type 2
      diabetes with (n = 458) and without (n = 318) clinically evident CVD were
      followed prospectively for cardiovascular events (cardiovascular death, non-fatal
      ischaemic stroke or myocardial infarction). CVD was classified according to the
      site (cerebrovascular disease, CHD, PAD); the extent of atherosclerosis was
      expressed as the number of affected sites. Carotid intima-media thickness and
      albuminuria were used as markers of atherosclerotic burden. RESULTS: Compared
      with patients with diabetes without CVD, the hazard ratio (HR) for a
      cardiovascular event was 3.8 (95% confidence interval 1.7, 8.5), adjusted for
      age, gender and potential confounders, in those with cerebrovascular disease, 4.3
      (1.9, 9.5) in those with CHD, and 4.6 (2.1, 10.2) in those with PAD. Findings
      were similar after additional adjustment for atherosclerotic burden. Adjusted HR
      was 3.4 (1.6, 6.9) for patients with diabetes with one affected site and 6.6
      (3.0, 14.3) for those with two or more sites. CONCLUSIONS: Patients with Type 2
      diabetes and cerebrovascular disease, CHD or PAD have strongly increased risks
      for future cardiovascular events which are comparable. This risk increases
      markedly with the number of different cardiovascular sites affected and is
      irrespective of atherosclerotic burden.

PMID- 18042080
TI  - Diagnostic potential of serum protein pattern in Type 2 diabetic nephropathy.
AB  - AIMS: Microalbuminuria is the earliest clinical sign of diabetic nephropathy
      (DN). However, the multifactorial nature of DN supports the application of
      combined markers as a diagnostic tool. Thus, another screening approach, such as
      protein profiling, is required for accurate diagnosis. Surface enhanced laser
      desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a novel
      method for biomarker discovery. We aimed to use SELDI and bioinformatics to
      define and validate a DN-specific protein pattern in serum. METHODS: SELDI was
      used to obtain protein or polypeptide patterns from serum samples of 65 patients
      with DN and 65 non-DN subjects. From signatures of protein/polypeptide mass, a
      decision tree model was established for diagnosing the presence of DN. We
      estimated the proportion of correct classifications from the model by applying it
      to a masked group of 22 patients with DN and 28 non-DN subjects. The weak
      cationic exchange (CM10) ProteinChip arrays were performed on a ProteinChip PBS
      IIC reader. RESULTS: The intensities of 22 detected peaks appeared up-regulated,
      whereas 24 peaks were down-regulated more than twofold (P < 0.01) in the DN group
      compared with the non-DN groups. The algorithm identified a diagnostic DN pattern
      of six protein/polypeptide masses. On masked assessment, prediction models based
      on these protein/polypeptides achieved a sensitivity of 90.9% and specificity of
      89.3%. CONCLUSION: These observations suggest that DN patients have a unique
      cluster of molecular components in serum, which are present in their SELDI
      profile. Identification and characterization of these molecular components will
      help in the understanding of the pathogenesis of DN. The serum protein signature,
      combined with a tree analysis pattern, may provide a novel clinical diagnostic
      approach for DN.

PMID- 18042081
TI  - An angled insertion technique using 6-mm needles markedly reduces the risk of
      intramuscular injections in children and adolescents.
AB  - AIMS: The aims of this study were (i) to establish which children with Type 1
      diabetes are at risk of intramuscular or intradermal insulin injections and (ii)
      to determine a needle length and technique that reliably administers insulin into
      subcutaneous fat. METHODS: Seventy-two healthy diabetic children (age 6.3-14.3
      years, body mass index standard deviation score 1.0 +/- 1.4) were recruited for
      study 1 and 37 of this cohort participated in study 2. In study 1, 200 microl air
      was injected into the abdomen and anterior thigh by a pinched skin-fold technique
      using either a perpendicular insertion of NovoFine(R) 31G 6-mm or an angled
      insertion of NovoFine(R) 30G 8-mm needles. In study 2, subjects received
      injections into abdomen and anterior thigh via angled 6-mm needles with either an
      unpinched or pinched technique. The site of air injection was visualized by
      ultrasound scan and measurements taken of subcutaneous fat thickness. RESULTS: In
      study 1, intramuscular injections were detected in 32% of subjects, and in a
      further 22% air was visualized at the muscle fascia. In study 2, intramuscular
      injections occurred in 3% of subjects and a further 11% had muscle fascia air
      detected. No intramuscular injections occurred in subjects injecting with a 6-mm
      needle and an angled pinched skin-fold technique. Pinching abdomen and thigh skin
      folds increased the subcutaneous fat thickness by 192 +/- 16% and 22 +/- 6%,
      respectively. In very lean subjects, pinching thighs actually reduced
      subcutaneous fat thickness. CONCLUSIONS: While intramuscular injections were
      observed frequently using standard injection protocols, an angled 6-mm needle
      technique reliably injects into the subcutaneous fat.

PMID- 18042082
TI  - A randomized cross-over trial to identify the optimal use of insulin glargine in
      prepubertal children using a three-times daily insulin regimen.
AB  - AIMS: The long-acting insulin analogue glargine reduces nocturnal hypoglycaemia
      and stabilizes morning blood glucose levels in patients with Type 1 diabetes
      (T1DM) on multiple injection therapy. However, young children may not tolerate
      such intensive insulin regimens. We investigated the effects of glargine in
      various three-injections-daily insulin combinations on 24-h glucose control in
      prepubertal children. METHODS: Seventeen T1DM prepubertal children (10 boys),
      median age 10.2 years (range 6.0-12.4), glycated haemoglobin (HbA(1c)) 8.8% (6.8
      11.5) were recruited to a randomized, open-label, cross-over study. After a 2
      week run-in period (with NPH pre-bed), every child underwent three different 3
      week treatment blocks in random order. All treatment blocks included glargine pre
      bed, but used different morning insulins: block 1, soluble only; block 2, soluble
      + NPH; block 3, aspart + NPH. Continuous glucose monitoring was performed for 3
      days at the end of the run-in and each treatment block. RESULTS: Compared with
      the run-in period on NPH, the three glargine treatment blocks were associated
      with lower (P < 0.0001) and less variable (P < 0.05) pre-breakfast glucose
      levels, and with an 8-15% reduction in total daily insulin dose (P < 0.0001).
      Risk of nocturnal hypoglycaemia detected by continuous glucose monitoring varied
      significantly between the three glargine treatment blocks, and was lowest when
      children were given aspart + NPH in the morning (block 3). CONCLUSION: Insulin
      glargine pre-bed can be used in three-injections-daily regimens in prepubertal
      children to lower and stabilize pre-breakfast glucose levels. However, to avoid
      the risk of nocturnal hypoglycaemia, the pre-bed glargine dose should be lowered
      by giving a further long-acting insulin, such as NPH, in the morning.

PMID- 18042083
TI  - Delayed initiation of subcutaneous insulin therapy after failure of oral glucose
      lowering agents in patients with Type 2 diabetes: a population-based analysis in
      the UK.
AB  - AIMS: The aim of this retrospective cohort study was to estimate the time to
      insulin initiation in patients with Type 2 diabetes inadequately controlled on
      oral glucose-lowering agents (OGLAs). METHODS: Insulin-naive patients failing on
      OGLAs were identified from The Health Improvement Network database, which
      collects records from general practices throughout the UK. Patients were included
      if they were aged > or = 40 years, had concomitant prescriptions for > or = 2
      OGLAs, and > or = 1 year of available records prior to the first occurrence of
      HbA(1c) > or = 8.0% after > or = 90 days of OGLA polytherapy at > or = 50% of
      maximum recommended dosages. RESULTS: A total of 2501 eligible patients with Type
      2 diabetes who had an HbA(1c) above the OGLA failure threshold of > or = 8.0%
      were identified (54.0% male; 30.9% aged 60-69 years). It was estimated that if
      all the eligible patients were followed for 5 years, 25% would initiate insulin
      within 1.8 years of OGLA failure (95% CI 1.6-2.0), and 50% within 4.9 years (95%
      CI 4.6-5.8). The presence of diabetes-related complications had no substantial
      impact on the time to insulin initiation. CONCLUSIONS: This study found that 25%
      of patients with Type 2 diabetes had insulin initiation delayed for at least 1.8
      years, and 50% of patients delayed starting insulin for almost 5 years after
      failure of glycaemic control with OGLA polytherapy, even in the presence of
      diabetes-related complications. Interventions that reduce this delay to insulin
      initiation are required to help achieve and maintain recommended glycaemic
      targets in patients with Type 2 diabetes.

PMID- 18042084
TI  - Quality of diabetes care in patients with schizophrenia and bipolar disorder:
      cross-sectional study.
AB  - AIMS: To determine whether patients with severe mental illness receive poorer
      health care for diabetes than patients without. METHODS: This population-based
      cross-sectional survey used electronic general practice records from 481 UK
      general practices contributing to the QRESEARCH database. The records of 11 043
      patients with diabetes, drawn from a database population of over 9 million
      patients, were extracted. Unadjusted and adjusted odds ratios were calculated
      using unconditional logistic regression for each of 17 quality indicators for
      diabetes care from the new General Medical Services contract for general
      practitioners. RESULTS: The presence of severe mental illness did not reduce the
      quality of care received; the only significant difference between groups showed
      that such patients were more likely to have glycated haemoglobin < 7.5%[adjusted
      odds ratio = 1.45 (99% confidence interval 1.20-1.76)]. Increasing age was
      associated with better care [adjusted odds ratios from 1.06 (1.02-1.11) to 1.61
      (1.52-1.70)], but other confounding variables had no consistent effect across
      indicators. Overall, performance against government targets was good.
      CONCLUSIONS: The hypothesis of poorer diabetes care for those with severe mental
      illness is disproved, perhaps surprisingly, in the light of other recent UK
      studies showing inequalities in care for the mentally ill. The study does not
      reveal who is providing this good care (general practitioners, psychiatrists or
      diabetologists) or take account of the estimated 600 000 people in the UK with
      undiagnosed diabetes.

PMID- 18042085
TI  - No evidence of association of the PDCD1 gene with Type 1 diabetes.
AB  - AIMS: To test the association between the immunoreceptor PD-1 (PDCD1) gene and
      Type 1 diabetes mellitus (T1DM). This gene has been reported to be associated
      with other autoimmune diseases such as systemic lupus erythematosus (SLE) as well
      as T1DM. METHODS: Genotyping of single nucleotide polymorphisms (SNPs) in the
      PDCD1 gene was performed using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP), pyrosequencing and TaqMan in two separate cohorts
      of Swedish patients and control subjects: a family study consisting of 184
      multiplex and eight simplex families and a case-control study consisting of 586
      patients and 836 control subjects. Three SNPs were genotyped: PD-1 7146, PD-1
      7785 and PD-1 8738. RESULTS: We did not detect any association or linkage between
      SNPs in PDCD1 and T1DM. We further performed a meta-analysis for association of
      PD-1 7146, PD-1 7785 and PD-1 8738 to T1DM. We detected heterogeneity in
      association with weak evidence for overall association. CONCLUSIONS: We conclude
      that PDCD1 is unlikely to be a major susceptibility gene for T1DM.

PMID- 18042086
TI  - Climbers with diabetes do well on Mount Kilimanjaro.

PMID- 18042087
TI  - Use of metformin according to estimated glomerular filtration rate: the threshold
      and the equation are important.

PMID- 18042089
TI  - Estimated glomerular filtration rate (eGFR) and metformin.

PMID- 18042090
TI  - [Founding the new German Skin Research Center].

PMID- 18042091
TI  - Diagnosis of oral squamous cell carcinoma and its precursor lesions.
AB  - Improvement of survival rate and quality of life after treatment of oral squamous
      cell carcinoma as well as cost reduction requires reliable early diagnosis of the
      tumor and its precursor lesions. Four different screening methods are primarily
      employed: toluidine blue staining (visually detected lesions: sensitivity 70
      100%, specificity 25-67%), photodynamic diagnosis (sensitivity 94-99%,
      specificity 60-89%), autofluorescence (no data published so far) and modern oral
      cytology (sensitivity 80%,specificity 95-100%). Additional analytic procedures
      such automated image analysis, DNA image cytometry and immunocytochemistry can be
      used to enhance the low sensitivity of conventional oral cytology. While these
      methods have achieved sensitivity and specificity approaching 100%, the studies
      involved clearly-defined entities such as large oral squamous cell carcinomas and
      aphthae. The modern and methodenhanced oral cytology is a simple, value-based and
      inexpensive tool for early diagnosis of oral squamous cell carcinoma and its
      precursor lesions. Surgical biopsy and histopathological examination remains the
      gold standard for definitive diagnosis.

PMID- 18042092
TI  - Embolia cutis medicamentosa following subcutaneous injection of glatiramer
      acetate.
AB  - Embolia cutis medicamentosa (ECM) is a rare side effect observed primarily after
      intramuscular injections. It is associated with localized, sometimes extensive
      necrosis of the skin. Reflex vasospasm induced by the injection trauma may be
      etiologically involved. It is a potentially serious reaction which is little
      influenced by which drug is injected. A patient developed typical ECM after
      subcutaneous selfinjection of glatiramer acetate for multiple sclerosis. This
      case is remarkable since 1) ECM developed after subcutaneous and not after
      intramuscular injection, 2) the injection was given by the patient himself, and
      3) glatiramer acetate can induce skin necrosis as a side effect. ECM can be
      easily differentiated from the latter by its typical clinical features.

PMID- 18042093
TI  - Clinical manifestations of cutaneous lupus erythematosus.
AB  - Cutaneous lupus erythematosus (CLE) is a chronic inflammatory autoimmune disease
      with a broad spectrum of clinical manifestations and a variable course. In
      numerous investigations, it has been shown that exogenous factors, such as UV
      light and drugs, can induce this disease. However, not all clinical aspects can
      be explained and therefore, the pathogenesis of CLE is currently under extensive
      research. The various cutaneous manifestations of LE are divided into LE
      nonspecific and LE-specific skin disease based on histologic criteria. LE
      nonspecific manifestations are mostly associated with systemic LE but can also
      occur in other diseases and include particularly vascular skin lesions such as pe
      riungual telangiectases. LE-specific skin disease includes the subtypes of CLE
      such as acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), chronic
      cutaneous LE (CCLE), and intermittent CLE (ICLE). The subdivision of these
      subtypes with different prognosis and course is supported by genetic, clinical,
      histologic, and immunoserologic findings. The subtypes of CLE require a specific
      morphological and clinical analysis, which is described in the first part of this
      review. In the second part of this review, further diagnostic procedures and
      therapeutic strategies in patients with CLE are discussed.

PMID- 18042094
TI  - [Band-like symmetric horizontal depression on both thighs].

PMID- 18042095
TI  - [Paratibial fasciotomy for postthrombotic leg ulcer using Vollmars fasciotome].

PMID- 18042098
TI  - Innovative endoscopy--research or patient care?

PMID- 18042099
TI  - Percutaneous endoscopic gastrostomy.

PMID- 18042100
TI  - Keeping pace with GI technology: knowing when to get out.

PMID- 18042101
TI  - Colonoscopy preparation: are our patients at risk?
AB  - Clinical studies are used to make generalizations about a population of interest.
      Bias can be defined as the systematic error in study design or implementation,
      leading to inaccurate generalizations about this population. There is a potential
      for bias in all of the clinical studies on sodium phosphate colonoscopy
      preparation, and this bias may lead to the differing conclusions regarding safety
      drawn by the authors. A review of some of the relevant literature is presented,
      as well as a discussion of propensity score analysis, a technique used to help
      clarify the causal pathway in nonrandomized studies. Based on the available
      information, it is reasonable to follow the recommendations contained in the
      consensus document of the American Society of Colon and Rectal Surgeons, American
      Society for Gastrointestinal Endoscopy, and Society of American Gastrointestinal
      and Endoscopic Surgeons regarding sodium phosphate colonoscopy preparation.

PMID- 18042102
TI  - A randomized prospective comparison of self-expandable plastic stents and
      partially covered self-expandable metal stents in the palliation of malignant
      esophageal dysphagia.
AB  - OBJECTIVES: Self-expanding metal stents (SEMS) provide effective palliation in
      patients with malignant dysphagia, although severe complications and mortality
      may result. We performed a prospective controlled trial to compare a new self
      expanding polyester mesh stent (Polyflex) with SEMS (Ultraflex). METHODS: One
      hundred one patients with unresectable esophageal carcinoma were randomized to
      placement of a Polyflex (N=47) or a partially covered Ultraflex (N=54) stent.
      Patients with esophagogastric junction (EGJ) malignancy were excluded. RESULTS:
      Placement was successful in 46 (98%) patients with the Polyflex and 54 (100%)
      patients with the Ultraflex stent. In one patient, the Polyflex stent could not
      be placed. After 1 wk, dysphagia was improved by at least 1 grade in 100% of the
      Polyflex group and in 94% of the Ultraflex group. Major complications were
      observed in 48% of the Polyflex group and 33% of the Ultraflex group.
      Intraprocedural perforation occurred in 1 Polyflex and 1 Ultraflex patient. Two
      Polyflex patients had postprocedural hemorrhage. Twenty (44%) patients with a
      Polyflex stent and 18 (33%) with an Ultraflex stent had recurrent dysphagia
      because of tumor overgrowth, stent migration, hyperplastic granulomatous
      reaction, or food bolus impaction. Multivariate analysis showed a significantly
      higher complication rate with Polyflex than with Ultraflex stents (odds ratio
      2.3, 95% CI 1.2-4.4). However, median survival was 134 days with Polyflex and 122
      days with Ultraflex stents (P=NS). CONCLUSIONS: No difference was seen in
      palliation of dysphagia between the two stents. Significantly more complications,
      especially late stent migration, were observed in the Polyflex group.

PMID- 18042103
TI  - Palliation of malignant esophageal Dysphagia: would you like plastic or metal?
AB  - Advanced esophageal carcinoma has a rather dismal prognosis with dysphagia to
      solids and liquids as a common symptom. Self-expanding metal stents provide
      immediate and durable relief of dysphagia. Recently, self-expanding plastic
      stents have been developed for refractory benign esophageal strictures but may
      have applications in malignant strictures as well. In this issue of The American
      Journal of Gastroenterology, a multicenter, prospective, randomized, comparative
      trial evaluates the safety and efficacy of self-expanding metal versus plastic
      stents for palliation of dysphagia due to esophageal cancer. While the stents
      compared equivalently for symptom relief, complications were observed more
      commonly in the plastic stent group.

PMID- 18042104
TI  - Should the quality of preparation impact postcolonoscopy follow-up
      recommendations?
AB  - A high-quality bowel cleansing preparation is an essential prerequisite for a
      safe, efficient, and accurate colonoscopy. Large studies, however, have shown
      that up to 25% of patients undergoing colonoscopy have what is considered to be
      an inadequate preparation. A well-done survey reported in this issue of the
      American Journal of Gastroenterology by Ben-Horin et al. found considerable
      variability among endoscopists in their assessment of preparation adequacy from
      photographs of three representative cases. When the preparation was judged
      suboptimal, follow-up colonoscopy often was recommended at shorter time intervals
      than is currently indicated by clinical guidelines. Because this practice is not
      supported by any direct investigation, a better practice might be to determine if
      the preparation is poor or inadequate, indicating instead the need for a prompt
      repeat preparation and another colonoscopy.

PMID- 18042105
TI  - Abdominal ultrasound for diagnosis of nonalcoholic fatty liver disease (NAFLD).
AB  - Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of
      chronic liver disease. The progressive subtype of NAFLD or nonalcoholic
      steatohepatitits (NASH), may progress to cirrhosis and its complications.
      Unfortunately, accurate noninvasive modalities for diagnosing NASH and monitoring
      its progression are unavailable, necessitating a liver biopsy. Abdominal
      ultrasound (US) is widely used for screening asymptomatic patients with an
      incidental elevation of liver enzymes. However, US cannot detect small amounts of
      hepatic steatosis and cannot establish the diagnosis of NASH or stage of hepatic
      fibrosis. In this issue of AJG, a new radiologic scoring system has been reported
      to have excellent performance in diagnosing NAFLD and visceral obesity. However,
      the utility of this scoring system in establishing the diagnosis of NASH and
      hepatic fibrosis, has not been shown. Additionally, validity of this scoring
      system to other populations (i.e. obese) and in the setting of private practice
      must be proven. In summary, this study provides some valuable data regarding the
      utility of radiologic modalities in detecting hepatic steatosis and abdominal fat
      but still falls short in answering some important diagnostic and prognostic
      questions in NAFLD. The evolving field of diagnostic imaging for NAFLD holds
      promise. A combination of serum biomarkers and radiologic modalities may one day
      provide the best diagnostic approach for patients with NAFLD, and potentially
      replace the necessity for liver biopsy in most patients.

PMID- 18042106
TI  - Health-related quality of life during natalizumab maintenance therapy for Crohn's
      disease.
AB  - OBJECTIVES: We evaluated the effects of treatment on health-related quality of
      life (HRQoL) during a randomized controlled trial of natalizumab maintenance
      therapy (ENACT-2) using both disease-specific and generic measures. METHODS:
      Crohn's disease patients who received natalizumab as induction therapy in ENACT-1
      (N=724) and responded (N=339) were re-randomized to ENACT-2 in which they
      received natalizumab 300 mg (N=168) or placebo (N=171) every 4 wk for 48
      additional wk. Outcome measures were the change from baseline on the inflammatory
      bowel disease questionnaire (IBDQ), the short form-36 (SF-36), the EuroQol-5D (EQ
      5D), and a subject global assessment. RESULTS: At entry into ENACT-1, scores
      indicated substantially impaired HRQoL for both the disease-specific and general
      measures. Natalizumab responders showed clinically meaningful improvement in
      HRQoL over the course of the ENACT-1 study. During maintenance therapy, IBDQ and
      SF-36 scale scores of patients who responded to natalizumab induction and were re
      randomized to receive the drug in ENACT-2 (N=168) remained stable, while those re
      randomized to placebo (N=171) worsened. At week 60, 48 wk after the initiation of
      maintenance therapy, the mean change from ENACT-1 baseline of all scales of the
      IBDQ and the SF-36 was significantly higher for those who continued to receive
      natalizumab (P<0.001 for all scales). The scores of patients who received
      maintenance natalizumab treatment were not statistically different from those of
      a cross-section of the U.S. population for 6 of 8 scales of the SF-36.
      CONCLUSIONS: The substantial improvement in HRQoL experienced by patients who
      responded to natalizumab induction therapy was maintained during an additional 48
      wk of maintenance therapy.

PMID- 18042107
TI  - Towards a nondualistic approach to multisystem illness.
AB  - There is an increasing interest in understanding the etiology and treatment of
      patients who present with multiple chronic symptoms. The thesis of this comment
      is that the understanding of these problems and progress on effective treatment
      will be greatly enhanced by emerging new models that go beyond dualistic
      distinctions like those between organic versus functional disorders and
      psychological versus physiological causation. The outline of this new model
      includes a focus on common neurobiological and behavioral mechanisms that operate
      across disorders including altered pain modulation, affect regulation, and
      illness coping. Exciting new areas of research include functional and structural
      brain imaging studies and more recent studies linking imaging with genetic
      markers, behavior, and autonomic responses. These new studies, carried out across
      illness populations, hold great promise to tie together the data on psychosocial,
      genetic, and biological mechanisms of these complicated clinical problems.

PMID- 18042108
TI  - The changing face of Clostridium difficile: what treatment options remain?
AB  - In this issue of the Journal, an article by Pepin et al. documents the shifting
      sands of the modern-day Clostridium difficile epidemic as seen in Quebec. Pepin
      and coauthors' observation that the superior activity of vancomycin over
      metronidazole has been lost since the emergence there of the hypervirulent strain
      NAP1/027 in 2003 has implications for the future treatment of C. difficile
      associated diarrhea (CDAD). This editorial explores these, particularly in
      complicated cases and high-risk populations.

PMID- 18042110
TI  - Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn's
      disease.
AB  - BACKGROUND: The thiopurines, azathioprine and 6-mercaptopurine, are traditional
      first-line immunomodulatory agents in adult and pediatric Crohn's disease, but
      the comparative efficacy and safety of methotrexate have seldom been examined. We
      report outcomes with methotrexate treatment in pediatric patients previously
      refractory to or intolerant of thiopurines. METHODS: In a four-center,
      retrospective cohort study, efficacy of methotrexate in maintaining remission was
      assessed by PCDAI measurements, steroid use, and height velocity. Patients served
      as their own historical controls. Multivariable analysis controlled for route of
      methotrexate administration, reason for thiopurine discontinuation, baseline
      disease activity, and disease duration. RESULTS: Forty-two percent of 60 children
      treated with methotrexate were in clinical remission without steroids at both 6
      and 12 months. A strong steroid sparing effect was observed compared with the
      year prior to methotrexate (P<0.001). Success rates were similar in previously
      thiopurine-intolerant and refractory patients. Height velocity increased from 
      1.9 SDS to -0.14 SDS (P=0.004) in the year following therapy. In a median 3-yr
      follow-up, a third of the patients did not require escalation of therapy; the
      others required step-up therapy with infliximab or surgery. Eight children (13%)
      stopped methotrexate due to adverse events, including, most commonly, elevated
      liver enzymes, and one serious episode of sepsis. CONCLUSION: Methotrexate
      appears effective in maintaining remission in pediatric Crohn's disease, when
      thiopurines have failed. Consideration should be given to its use earlier in
      pediatric treatment algorithms.

PMID- 18042112
TI  - Cyclic vomiting syndrome: what a gastroenterologist needs to know.
AB  - BACKGROUND: CVS (cyclic vomiting syndrome) is a functional disorder that may
      occur in any age group of patients. In the past the disorder was considered to be
      fairly uncommon of unknown etiology. Treatment has generally been based on
      anecdotal reports. METHODS: Literature review was performed based on
      internet/Medline search as of April 2006. RESULTS: CVS is much more common than
      previously thought, especially in adults and is commonly associated with migraine
      headaches and sharing many of its characteristic features. Genetic association
      with mitochondrial DNA has been recognized with CVS. Prompt diagnosis is
      essential in order to prevent the significant morbidity associated with CVS. It
      is mandatory to rule out certain life-threatening disorders that can mimic CVS.
      Treatment options are based on the particular phase of the syndrome in which a
      patient is in and carried out in a systematic manner. CONCLUSION: Expert
      consensus is that CVS is a distinct disorder and is a part of the migraine
      spectrum (migraine headaches, CVS, and abdominal migraines). Once patients are
      properly diagnosed, treatment is highly effective. Because of renewed interest in
      CVS since the 1990's, many more patients in all age groups are being recognized
      who suffer from this disabling disorder. An increase in basic science and
      clinical research in CVS will hopefully lead to better patient outcomes.

PMID- 18042114
TI  - Banding ligation versus beta-blockers as primary prophylaxis in esophageal
      varices: systematic review of randomized trials.
AB  - OBJECTIVE: To compare banding ligation versus beta-blockers as primary
      prophylaxis in patients with esophageal varices and no previous bleeding.
      METHODS: Randomized trials were identified through electronic databases,
      reference lists in relevant articles, and correspondence with experts. Three
      authors extracted data. Random effects meta-analysis and metaregression were
      performed. The reported allocation sequence generation and concealment were
      extracted as measures of bias control. RESULTS: The initial searches identified
      1,174 references. Sixteen trials were included. In 15 trials, patients had high
      risk varices. Three trials reported adequate bias control. All trials reported
      mortality for banding ligation (116/573 patients) and beta-blockers (115/594
      patients). Mortality in the two treatment groups was not significantly different
      in the trials with adequate bias control (relative risk 1.22, 95% CI 0.84-1.78)
      or unclear bias control (RR 1.02, 95% CI 0.75-1.39). Trials with adequate bias
      control found no significant difference in bleeding rates (RR 0.86, 95% CI 0.55
      1.35). Trials with unclear bias control found that banding ligation significantly
      reduced bleeding (RR 0.56, 95% CI 0.41-0.77). Both treatments were associated
      with adverse events. In metaregression analyses, the estimated effect of ligation
      was significantly more positive if trials were published as abstracts. Likewise,
      the shorter the follow-up, the more positive the estimated effect of ligation.
      CONCLUSIONS: Banding ligation and beta-blockers may be used as primary
      prophylaxis in high-risk esophageal varices. The estimated effect of banding
      ligation in some trials may be biased and was associated with the duration of
      follow-up. Further high-quality trials are still needed.

PMID- 18042116
TI  - Post-sphincterotomy bleeding: who, what, when, and how.
AB  - Endoscopic biliary sphincterotomy (ES) is the cornerstone of therapeutic
      endoscopic retrograde cholangiopancreatography (ERCP). Bleeding is one of the
      most frequent complications following ES. Rates of post-ES bleeding vary widely
      and its presentation may be immediate (intraprocedural) or several days later.
      Clinically, bleeding can range from insignificant to life threatening. Most
      bleeding episodes are managed successfully by conservative measures with or
      without endoscopic therapy. Endoscopic treatment options include injection,
      thermal, and mechanical methods-alone or in combination. For refractory cases,
      angiographic embolization, or surgery, is necessary. Both technical risk factors
      and patient risk factors contribute to the development of post-ES bleeding. When
      these risk factors are present, measures can be taken to reduce the risk of
      bleeding. In this manuscript the literature on post-ES bleeding is reviewed.

PMID- 18042117
TI  - ERCP in acute biliary pancreatitis: the moor has done his duty, the moor may go.

PMID- 18042119
TI  - Improving transparency in medical journals.

PMID- 18042120
TI  - New modification of double-balloon endoscopy to reduce complications.

PMID- 18042121
TI  - Metastatic leiomyosarcoma diagnosed on routine screening colonoscopy.

PMID- 18042122
TI  - Acute lower gastrointestinal bleeding after ingestion of blister-wrapped tablet.

PMID- 18042123
TI  - Another case of severe, chronically symptomatic, nonhealing gastroduodenal injury
      after radioembolization of hepatic tumor.

PMID- 18042124
TI  - Coexistence of pyoderma gangrenosum and Sweet's syndrome in a patient with
      ulcerative colitis.

PMID- 18042127
TI  - Clinical practice algorithm: medication management to reduce fall risk in the
      elderly. Part 1.

PMID- 18042128
TI  - Preparation for negotiating scope of practice for acute care nurse practitioners.

PMID- 18042129
TI  - Benefits of hormone replacement therapy in postmenopausal women.
AB  - PURPOSE: To provide an overview of current research regarding hormone replacement
      therapy (HRT) and to assist healthcare providers to better educate patients about
      potential benefits of this therapy. DATA SOURCES: A systematic review of
      healthcare literature was conducted with 602 articles selected from CINAHL,
      Medscape, Pubmed, and Medline databases. Keywords directing the search included
      hormone replacement therapy, benefits of hormone replacement therapy and trends,
      hormone replacement therapy and osteoporosis, hormone replacement, and menopause
      symptoms. CONCLUSIONS: According to the literature, HRT can assist women with
      postmenopausal symptoms. In addition, research shows that HRT can help some
      postmenopausal women with selected comorbid conditions such as osteoporosis, type
      II diabetes, certain cardiovascular pathologies, and colorectal cancer. The
      decision as to who should use any form of HRT needs to be based on the individual
      woman's needs, quality of life, and potential risks versus benefits. IMPLICATIONS
      FOR PRACTICE: HRT has been a benefit to many women in the treatment of
      postmenopausal symptoms. Recent studies have shown that HRT, whether it is
      combined estrogen and progestin therapy, or estrogen-only therapy, can help
      postmenopausal women with osteoporosis and some selected comorbid conditions.
      Recent research indicates that some women are dying from comorbid conditions
      rather than breast cancer. Although the research regarding HRT in some areas may
      be limited, further research adds to existing knowledge and offers new ideas and
      possibilities in the treatment of postmenopausal symptoms and selected comorbid
      conditions. Certainly HRT can improve quality of life and possibly longevity for
      selected women. Ongoing research is needed to further validate such benefits, as
      well as to further explore the risks and benefits of long-term HRT. Increased
      knowledge about HRT will help healthcare providers better educate patients about
      the potential benefits of HRT, while providing documentation about who should
      take selected types of HRT or whether alternative treatment is preferred.

PMID- 18042130
TI  - Suboptimal vitamin D status is a highly prevalent but treatable condition in both
      hospitalized patients and the general population.
AB  - PURPOSE: To heighten awareness of the problems related to the high prevalence of
      suboptimal vitamin D status in hospitalized patients and the general population,
      including an overview of vitamin D biology, how vitamin D status is defined, the
      negative health issues associated with suboptimal vitamin D status, indications
      for treatment, treatment strategies, and controversies in the field. DATA
      SOURCES: (a) Literature review was performed using PubMed and CINAHL databases to
      locate and review medical, nursing, and nutritional journals. (b) Authors' recent
      prospective studies of 100 patients in a general tertiary hospital rehabilitation
      unit and 51 nonhospitalized volunteers. CONCLUSION: Poor vitamin D status
      (ranging from suboptimal to overt deficiency) is common in both hospitalized
      patients and ostensibly healthy individuals of all ages and geographic latitude.
      Suboptimal vitamin D status is associated with muscle weakness, functional
      deficits, and perhaps longer length of stay of hospitalized patients. Predictors
      of vitamin D status include race, poor nutrition, advanced age, use of
      multivitamins, ultraviolet light exposure, and grip strength. Fortunately,
      treatment with 50,000 IU of vitamin D(2) for several weeks is a very inexpensive
      and safe yet effective treatment to replete vitamin D status. IMPLICATIONS FOR
      PRACTICE: NPs should be aware of the indications for monitoring vitamin D status
      and the appropriate treatment for suboptimal vitamin D status. Improving vitamin
      D status may improve a patient's functional ability, therefore decreasing falls
      and preventing fractures, decreasing length of stay in the hospital, and
      decreasing the cost of health care. Providers can potentially improve the life of
      older adults by educating patients on the importance of vitamin D
      supplementation.

PMID- 18042131
TI  - A qualitative analysis of how advanced practice nurses use clinical decision
      support systems.
AB  - PURPOSE: The purpose of this study was to generate a grounded theory that will
      reflect the experiences of advanced practice nurses (APNs) working as critical
      care nurse practitioners (NPs) and clinical nurse specialists (CNS) with computer
      based decision-making systems. DATA SOURCES: A study design using grounded theory
      qualitative research methods and convenience sampling was employed in this study.
      Twenty-three APNs (13 CNS and 10 NPs) were recruited from 16 critical care units
      located in six large urban medical centers in the U.S. Midwest. Single-structured
      in-depth interviews with open-ended audio-taped questions were conducted with
      each APN. Through this process, APNs defined what they consider to be relevant
      themes and patterns of clinical decision system use in their critical care
      practices, and they identified the interrelatedness of the conceptual categories
      that emerged from the results. Data were analyzed using the constant comparative
      analysis method of qualitative research. CONCLUSIONS: APN participants were
      predominantly female, white/non-Hispanic, had a history of access to the clinical
      decision system used in their critical care settings for an average of 14 months,
      and had attended a formal training program to learn how to use clinical decision
      systems. "Forecasting decision outcomes," which was defined as the voluntary
      process employed to forecast the outcomes of patient care decisions in critical
      care prior to actual decision making, was the core variable describing system use
      that emerged from the responses. This variable consisted of four user constructs
      or components: (a) users' perceptions of their initial system learning
      experience, (b) users' sense of how well they understand how system technology
      works, (c) users' understanding of how system inferences are created or derived,
      and (d) users' relative trust of system-derived data. Each of these categories
      was further described through the grounded theory research process, and the
      relationships between the categories were identified. IMPLICATIONS FOR PRACTICE:
      The findings of this study suggest that the main reason critical care APNs choose
      to integrate clinical decision systems into their practices is to provide an
      objective, scientifically derived, technology-based backup for human forecasting
      of the outcomes of patient care decisions prior to their actual decision making.
      Implications for nursing, health care, and technology research are presented.

PMID- 18042132
TI  - Florida nurse practitioners' attitudes and practices regarding oral cancer
      prevention and early detection.
AB  - PURPOSE: To examine Florida nurse practitioners' (NPs') attitudes and practices
      regarding oral cancer prevention and early detection. DATA SOURCE: A statewide
      mail survey was conducted among Florida NPs who provided primary care. The
      questionnaire was adapted from an existing survey instrument used to measure NPs'
      knowledge, attitudes, and practices about oral cancer prevention and early
      detection. A total of 448 Florida NPs (33% response rate) completed the survey.
      CONCLUSIONS: Florida NPs reportedly were not well prepared for oral cancer
      prevention and early detection. Although most NPs realized the importance of
      annual oral cancer screening for high-risk populations and held positive
      attitudes toward the benefit of early detection, only 39.3% of respondents
      thought his or her knowledge about oral cancer was current and more than half had
      never provided oral cancer examinations. IMPLICATIONS FOR PRACTICE: Florida has
      among the nation's highest oral cancer rates, but persons at highest risk are
      among those least likely to see a dentist. Therefore, a multidisciplinary
      approach involving all relevant healthcare providers, including NPs, may be more
      effective than relying only on dentists' efforts in improving survival rates for
      oral cancer. Strategies are needed to increase the involvement of Florida's NPs
      in oral cancer detection.

PMID- 18042133
TI  - Nurse Practitioner Corporate Partner Council.

PMID- 18042134
TI  - Axonal Guillain-Barre syndrome: carbohydrate mimicry and pathophysiology.
AB  - Acute motor axonal neuropathy (AMAN), an axonal subtype of Guillain-Barre
      syndrome (GBS), is characterized by pure motor involvement, frequent antecedent
      infection by Campylobacter jejuni, association with anti-GM1 or anti-GD1a
      immunoglobulin G (IgG) antibodies, and the electrophysiological features of
      axonal degeneration and reversible conduction block. Molecular mimicry exists
      between GM1 and GD1a gangliosides and lipooligosaccharides (LOSs) of C. jejuni
      isolates from AMAN. Sensitization of rabbits with GM1 or C. jejuni LOS induces
      anti-GM1 IgG antibodies and subsequent flaccid paralysis. Pathological changes
      seen in rabbit model peripheral nerves are identical to those in human AMAN.
      Immunohistochemistry of AMAN rabbits shows disruption of nodal sodium channel
      clusters and detachment of paranodal myelin terminal loops, similar to paranodal
      demyelination, which would significantly reduce the safety factor for impulse
      transmission and might be responsible for the rapidly reversible conduction block
      frequently present in human AMAN. C. jejuni sialyltransferase (Cst-II), which
      functions in the biosynthesis of ganglioside-like LOSs, determines the
      transferase activity. Strains with cst-II (Thr51) express GM1 and GD1a epitopes,
      whereas GBS patients infected with cst-II (Thr51) strains have anti-GM1 or anti
      GD1a IgG antibodies. The cst-II gene is responsible for the development of GBS.
      Immunological, pathological, electrophysiological, and bacteriological studies
      have provided strong evidence of carbohydrate mimicry being a cause of AMAN and
      clarified the mechanisms of nerve conduction failure in AMAN.

PMID- 18042135
TI  - Selective changes in nocifensive behavior despite normal cutaneous axon
      innervation in leptin receptor-null mutant (db/db) mice.
AB  - Much of our understanding of the effects of diabetes on the peripheral nervous
      system is derived from models induced by streptozotocin in which hyperglycemia is
      rapidly caused by pancreatic beta-cell destruction. Here, we have quantified
      sensory impairments over time in leptin receptor (lepr)-null mutant -/- mice, a
      type 2 model of diabetes in which the absence of leptin receptor signaling leads
      to obesity and chronic hyperglycemia by 4 weeks of age. To assess these mice as a
      model for peripheral neuropathy, we quantified the responsiveness of lepr -/-
      mice to mechanical, thermal, and chemogenic stimuli, as well as epidermal and
      dermal innervation of the hind paw. Compared with wild-type +/+ and heterozygous
      +/- mice, lepr -/- mice displayed reduced sensitivity to mechanical stimuli by 6
      weeks of age, and however, responses to noxious heat were normal. Lepr -/- mice
      also devoted less activity to their injected paw during the second phase
      following formalin administration. However, epidermal and dermal innervation of
      lepr -/- mice was not different from that of lepr +/+ and +/- mice even after 10
      weeks of hyperglycemia, suggesting that cutaneous innervation is resistant to
      chronic hyperglycemia in these mice. These results suggest that certain rodent
      nocifensive behaviors may be linked to the abundance of cutaneous innervation,
      while others are not. Finally, these results reveal that the lepr -/- mice may
      not be useful to study neuropathy associated with distal axonal degeneration but
      may be better suited for studies of hyperglycemia-induced sensory neuron
      dysfunction without distal nerve loss.

PMID- 18042136
TI  - Diabetes does not accelerate neuronal loss following nerve injury.
AB  - To determine the resistance of neuronal dorsal root ganglion (DRG) cells in
      experimental diabetes, we studied the neuronal cell loss after severe axonal
      injury in streptozotocin (STZ) diabetic rats with unilateral transection of the
      L5 spinal nerve for 12 weeks. Fifty 18-week-old inbred male Wistar rats were
      randomly allocated to three study groups. In study group 1 without spinal nerve
      injury, STZ diabetes was induced in 9 and 10 rats were kept as nondiabetic
      controls. In study group 2, spinal nerve injury was performed in 10 diabetic rats
      and in 10 nondiabetic controls. In study group 3, six nondiabetic control rats at
      18 weeks and five nondiabetic control rats at 30 weeks were included to determine
      whether DRG cell changes occur without nerve injury during the study period. In
      group 1, the stereologically determined number of all neuronal DRG cells was
      unchanged after 12 weeks of diabetes. The mean perikaryal volume of neuronal DRG
      cells of the A and B subtypes was reduced by 10% each (p < 0.05). In group 2,
      spinal nerve injury led to neuronal cell loss, chromatolysis, and perikaryal
      shrinkage but without any acceleration of cell loss after 12 weeks of diabetes.
      In group 3, there were no changes indicating that the reduction of perikaryal
      volume in diabetic rats without nerve injury represents shrinkage. We conclude
      that neuronal DRG cells in rats are resistant to diabetes per se and that
      addition of diabetes for 12 weeks to spinal nerve injury does not further
      accelerate the cell loss.

PMID- 18042137
TI  - Interleukin-10 reduces scarring and enhances regeneration at a site of sciatic
      nerve repair.
AB  - Axonal regeneration at a site of peripheral nerve repair can be impeded by the
      formation of scar tissue, which creates a mechanical barrier and initiates the
      development of multiple branched axonal sprouts that form a neuroma. We have
      investigated the hypothesis that the application of a scar-reducing agent to the
      nerve repair site would permit better axonal regeneration. In anaesthetised C57
      Black-6 mice, the left sciatic nerve was sectioned and immediately re
      approximated using four epineurial sutures. In five groups of eight mice, we
      injected transforming growth factor-beta3 (50 or 500 ng), interleukin-10 (IL-10)
      (125 or 500 ng), or saline into and around the repair site, both before and after
      the nerve section. Another group of eight animals acted as sham-operated
      controls. After 6 weeks, the outcome was assessed by recording compound action
      potentials (CAPs), measuring collagen levels using picrosirius red staining, and
      counting the number of myelinated axons proximal and distal to the repair. CAPs
      evoked by electrical stimulation distal to the repair were significantly smaller
      in all repair groups except for the low-dose IL-10 group, where they were not
      significantly different from that in controls. The area of staining for collagen
      had significantly increased in all repair groups except for the low-dose IL-10
      group, which was not significantly different from that in controls. The
      myelinated fibre counts were always higher distal to the repair site, but there
      were no significant differences between groups. We conclude that administration
      of a low-dose of IL-10 to a site of sciatic nerve repair reduces scar formation
      and permits better regeneration of the damaged axons.

PMID- 18042138
TI  - Modulation of intracellular calcium influences capsaicin-induced currents of TRPV
      1 and voltage-activated channel currents in nociceptive neurones.
AB  - Modulation of intracellular calcium ([Ca2+](i)) has a major impact on processing
      of nociceptive signals. While activation of the transient receptor potential
      vanilloid-1 (TRPV-1) receptor/channel complex increases [Ca2+](i) by Ca2+ entry
      from the extracellular space, as well as by Ca2+ release from intracellular
      stores, the Ca2+ entry through voltage-activated calcium channels (VACCs) is
      modulated simultaneously. To clarify the relations between [Ca2+](i) and the
      activation of TRPV-1 receptor and VACC currents [I(TRPV-1) and I(Ca(V))], we
      performed voltage clamp experiments using Ba2+ as well as Ca2+ as a charge
      carrier. The TRPV-1 receptor was activated by the application of 0.5 microM
      capsaicin, and the currents through TRPV-1 and VACC [I(TRPV-1) and I(Ca(V))] were
      measured either when Ca2+ release from intracellular stores was pharmacologically
      promoted or prevented. With Ba2+ as the divalent charge carrier, capsaicin (0.5
      microM) reduced I(Ca(V)) (elicited by a depolarization to 0 mV) to 52.7 +/- 4.5%
      of baseline, and the elicited current through the TRPV-1 receptor/channel complex
      was 6.6 +/- 0.9% [relative to peak I(Ca(V))]. These currents were significantly
      different when Ca2+ was used as charge carrier: the I(Ca(V)) reductions were
      decreased to 17.8 +/- 5.9% of baseline, while the I(TRPV-1) was as high as 57.1
      +/- 9.1% of I(Ca(V)). Increases of [Ca2+](i) by releasing Ca2+ from intracellular
      stores (using caffeine, 10 mM) before the application of capsaicin increased the
      I(TRPV-1) (14.1 +/- 7%), while the I(Ca(V)) was decreased to 51.6 +/- 4.9%
      compared with control. A preexperimental partial reduction of the Ca2+ release
      from the stores by dantrolene (5 microM) resulted in less pronounced effects
      [24.5 +/- 8.8%, relative to peak I(Ca(V))] for I(TRPV-1), and a reduction to 35.4
      +/- 3% of baseline for I(Ca(V)) after capsaicin application.

PMID- 18042139
TI  - Incidence of Guillain-Barre syndrome in Germany.

PMID- 18042140
TI  - Hemorrhagic polyneuropathy in idiopathic thrombocytopenic purpura.

PMID- 18042141
TI  - Transient hypertrichosis in a patient with Guillain-Barre syndrome.

PMID- 18042142
TI  - Cancer genomics.
AB  - Almost all cells in the human body contain a complete copy of the genome with an
      estimated number of 25,000 genes. The sequences of these genes make up about
      three percent of the genome and comprise the inherited set of genetic
      information. The genome also contains information that determines when and where
      in the organism a given gene is active. This is the epigenetic information.
      Genomics is the study of DNA sequences and the epigenetic information of gene
      regulation.

PMID- 18042143
TI  - Epigenetic changes in cancer.
AB  - A cancer develops when a cell acquires specific growth advantages through the
      stepwise accumulation of heritable changes in gene function. Basically, this
      process is directed by changes in two different classes of genes: Tumor
      suppressor genes that inhibit cell growth and survival and oncogenes that promote
      cell growth and survival. Since several alterations are usually required for a
      cancer to fully develop, the malignant phenotype is determined by the compound
      status of tumor suppressor genes and oncogenes. Cancer genes may be changed by
      several mechanisms, which potentially alter the protein encoding nucleotide
      template, change the copy number of genes, or lead to increased gene
      transcription. Epigenetic alterations, which, by definition, comprise mitotically
      and meiotically heritable changes in gene expression that are not caused by
      changes in the primary DNA sequence, are increasingly being recognized for their
      roles in carcinogenesis. These epigenetic alterations may involve covalent
      modifications of amino acid residues in the histones around which the DNA is
      wrapped, and changes in the methylation status of cytosine bases (C) in the
      context of CpG dinucleotides within the DNA itself. Methylation of clusters of
      CpGs called "CpG-islands" in the promoters of genes has been associated with
      heritable gene silencing. The present review will focus on how disruption of the
      epigenome can contribute to cancer. In contrast to genetic alterations, gene
      silencing by epigenetic modifications is potentially reversible. Treatment by
      agents that inhibit cytosine methylation and histone deacetylation can initiate
      chromatin decondensation, demethylation and reestablishment of gene
      transcription. Accordingly, in the clinical setting, DNA methylation and histone
      modifications are very attractive targets for the development and implementation
      of new therapeutic approaches. Many clinical trials are ongoing, and epigenetic
      therapy has recently been approved by the United States Food and Drug
      Administration (US FDA) for use in the treatment of myelodysplastic syndrome
      (MDS) and primary cutaneous T-cell lymphoma (CTCL).

PMID- 18042144
TI  - Chromatin-modifying proteins in cancer.
AB  - Chromatin-modifying proteins mold the genome into areas that are accessible for
      transcriptional activity and areas that are transcriptionally silent. This
      epigenetic gene regulation allows for different transcriptional programs to be
      conducted in different cell types at different timepoints-despite the fact that
      all cells in the organism contain the same genetic information. A large amount of
      data gathered over the last decades has demonstrated that deregulation of
      chromatin-modifying proteins is etiologically involved in the development and
      progression of cancer. Here we discuss how epigenetic alterations influence
      cancer development and review known cancer-associated alterations in chromatin
      modifying proteins.

PMID- 18042145
TI  - MicroRNAs and cancer.
AB  - MicroRNAs (miRNAs) are a recently discovered group of small RNA molecules
      involved in the regulation of gene expression. Analogously to mRNAs, the non
      protein-encoding pri-miRNAs are synthesized by RNA polymerase II and post
      transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail.
      Subsequently, the pri-miRNA undergoes a number of processing steps in the nucleus
      and cytoplasm, and ends up as a mature approximately 22 nt miRNA, which can exert
      its function by binding to the 3'-untranslated region of a subset of mRNAs.
      Binding of the miRNA to the mRNA results in a reduced translation rate and/or
      increased degradation of the mRNA. In this way a large number of cellular
      pathways, such as cellular proliferation, differentiation, and apoptosis, are
      regulated by mi-RNAs. As corruption of these pathways is the hallmark of many
      cancers, dysregulation of miRNA biogenesis or expression levels may lead to
      tumorigenesis. The mechanisms that alter the expression of miRNAs are similar to
      those that change the expression levels of mRNAs of tumor suppressor- and
      oncogenes, i.e. gross genomic aberrations, epigenetic changes, and minor
      mutations affecting the expression level, processing, or target-interaction
      potential of the miRNA. Furthermore, expression profiling of miRNAs has been
      found to be useful for classification of different tumor types. Taken together,
      miRNAs can be classified as onco-miRs or tumor suppressor-miRs, and may turn out
      to be potential targets for cancer therapy.

PMID- 18042146
TI  - Combining array-based approaches for the identification of candidate tumor
      suppressor loci in mature lymphoid neoplasms.
AB  - Tumor suppressor gene (TSG) inactivation by chromosomal deletions and/or
      mutations is a well-characterized genetic alteration in lymphomas. Array-based
      technologies have greatly increased the detection and characterization of
      chromosomal imbalances and regions with loss of heterozygosity (LOH), leading to
      the identification of a number of novel candidate TSG loci. In addition,
      microarray platforms for studying DNA methylation and histone modifications
      enable identifying epigenetic changes affecting gene expression of TSG. Combining
      these microarray technologies with gene expression profiling is a promising
      strategy to discover novel TSG in regions targeted by genetic or epigenetic
      alterations. In this review we present an outline of methodological aspects of
      the various microarray technologies, and discuss their potentials and
      restrictions. Furthermore, we survey research findings derived from these high
      throughput techniques, which are allowing a deeper insight into the mechanisms of
      lymphomagenesis.

PMID- 18042147
TI  - Diagnostic and prognostic significance of gene expression profiling in lymphomas.
AB  - Gene expression profiling is a powerful tool to uncover complex molecular
      networks in cancer and, specifically, in malignant lymphomas. Within diffuse
      large B-cell lymphomas (DLBCL), two major molecular subtypes, the activated B
      cell-like (ABC) and the germinal center B-cell-like (GCB) DLBCL, can be defined.
      Compared to GCB DLBCL, ABC DLBCL shows a vast difference in gene expression and
      constitutively expresses NFkappaB and its target genes. In retrospective
      analyses, the molecular phenotype of ABC DLBCL is associated with inferior
      survival. Gene expression profiling furthermore allows the molecular separation
      of Burkitt lymphoma (BL) from DLBCL and reveals a Burkitt-specific signature
      which is also expressed by a subset of tumors that are currently classified as
      DLBCL. Whether patients with a DLBCL displaying a Burkitt-specific gene
      expression signature may benefit from alternative therapeutic approaches will
      have to be determined in future prospective clinical trials. In follicular
      lymphoma (FL), two outcome-related signatures, termed Immune response 1 (IR1) and
      Immune response 2 (IR2), have been identified by gene expression profiling,
      indicating a significant role of the microenvironment in tumor development and
      progression. IR1, composed of genes mostly expressed by T-cells, was found to be
      associated with a more favorable clinical course, and IR2, enriched for genes
      expressed by macrophages and follicular dendritic cells, was found to be
      associated with an inferior clinical course. In mantle cell lymphoma (MCL), a
      gene expression-based proliferation signature of 20 different genes was
      identified that is able to predict survival of MCL patients in a linear fashion.
      Future efforts will have to be directed towards the translation of relevant
      molecular diagnostic and prognostic markers derived from the wealth of gene
      expression data into clinical tests and towards the development of novel,
      targeted therapies.

PMID- 18042148
TI  - The epigenome of testicular germ cell tumors.
AB  - Gene expression is tightly regulated in normal cells, and epigenetic changes
      disturbing this regulation are a common mechanism in the development of cancer.
      Testicular germ cell tumor (TGCT) is the most common malignancy among young males
      and can be classified into two main histological subgroups: seminomas, which are
      basically devoid of DNA methylation, and nonseminomas, which in general have
      methylation levels comparable with other tumor tissues, as shown by restriction
      landmark genome scanning (RLGS). In general, DNA methylation seems to increase
      with differentiation, and among the nonseminomas, the pluripotent and
      undifferentiated embryonal carcinomas harbor the lowest levels of DNA promoter
      hypermethylation, whereas the well-differentiated teratomas display the highest.
      In this regard, TGCTs resemble the early embryogenesis. So far, only a limited
      number of tumor suppressor genes have been shown to be inactivated by DNA
      promoter hypermethylation in more than a minor percentage of TGCTs, including
      MGMT, SCGB3A1, RASSF1A, HIC1, and PRSS21. In addition, imprinting defects, DNA
      hypomethylation of testis/cancer associated genes, and the presence of
      unmethylated XIST are frequent in TGCTs. Aberrant DNA methylation has the
      potential to improve current diagnostics by noninvasive testing and might also
      serve as a prognostic marker for treatment response.

PMID- 18042149
TI  - The genome and epigenome of malignant melanoma.
AB  - Malignant melanoma originates in melanocytes, the pigment-producing cells of the
      skin and eye, and is one of the most deadly human cancers with no effective cure
      for metastatic disease. Like many other cancers, melanoma has both environmental
      and genetic components. For more than 20 years, the melanoma genome has been
      subject to extensive scrutiny, which has led to the identification of several
      genes that contribute to melanoma genesis and progression. Three molecular
      pathways have been found to be nearly invariably dysregulated in melanocytic
      tumors, including the RAS-RAF-MEK-ERK pathway (through mutation of BRAF, NRAS or
      KIT), the p16 INK4A-CDK4-RB pathway (through mutation of INK4A or CDK4) and the
      ARF-p53 pathway (through mutation of ARF or TP53). Less frequently targeted
      pathways include the PI3K-AKT pathway (through mutation of NRAS, PTEN or PIK3CA)
      and the canonical Wnt signaling pathway (through mutation of CTNNB1 or APC).
      Beyond the specific and well-characterized genetic events leading to activation
      of proto-oncogenes or inactivation of tumor suppressor genes in these pathways,
      systematic high-resolution genomic analysis of melanoma specimens has revealed
      recurrent DNA copy number aberrations as well as perturbations of DNA methylation
      patterns. Melanoma provides one of the best examples of how genomic analysis can
      lead to a better understanding of tumor biology. We review current knowledge of
      the genes involved in the development of melanoma and the molecular pathways in
      which these genes operate.

PMID- 18042150
TI  - Expression, phosphorylation, and mRNA-binding of heterogeneous nuclear
      ribonucleoprotein K in Xenopus oocytes, eggs, and early embryos.
AB  - Here we show that heterogeneous nuclear ribonucleoprotein K (hnRNP K), a member
      of the K homology domain-containing proteins, is expressed in Xenopus immature
      oocytes, unfertilized eggs, and early embryos. Fertilization or egg activation
      treatment involving upregulation of the egg tyrosine kinase Src promotes a rapid
      and transient tyrosine phosphorylation of hnRNP K. HnRNP K is also phosphorylated
      on serine/threonine residues in unfertilized eggs, dephosphorylated after
      fertilization, and re-phosphorylated during the premitotic phase of early
      embryogenesis. In vitro, Src and mitogen-activated protein kinase (MAPK) were
      capable of phosphorylating hnRNP K on tyrosine and serine/threonine residues,
      respectively. In support of this, pretreatment of oocytes, eggs, or embryos with
      inhibitors for Src (PP2) and MAPK (U0126) blocked effectively the phosphorylation
      of hnRNP K. We also identify some maternal mRNAs that coimmunoprecipitate with
      hnRNP K in unfertilized eggs. Specific binding of these mRNAs to hnRNP K was
      verified by reverse transcriptase-polymerase chain reaction (RT-PCR). In
      addition, real-time PCR analyses revealed a subset of the mRNAs whose binding to
      hnRNP K might be up or downregulated in activated eggs. In vitro binding assay
      with the use of poly U monopolymeric RNA-coupled beads demonstrated that the RNA
      binding property of hnRNP K is negatively regulated by tyrosine phosphorylation
      and positively or neutrally regulated by serine/threonine phosphorylation. Taken
      together, it is attractive to suggest that hnRNP K is in association with certain
      pools of maternal mRNAs whose translational activation are modulated by the
      Src/MAPK phosphorylation of hnRNP K during oocyte-egg-embryo transition.

PMID- 18042151
TI  - Branding the seal branders: what does the research say about seal branding?

PMID- 18042152
TI  - Investigator responsibilities and animal welfare issues raised by hot branding of
      pinnipeds.

PMID- 18042153
TI  - Hot iron branding of seals and sea lions: why the ban will remain.

PMID- 18042154
TI  - Comparison of radioimmunoassay and chemiluminescent assay methods to estimate
      canine blood cortisol concentrations.
AB  - BACKGROUND: Non-radioactive assay methods are widely used in commercial
      laboratories to measure canine blood cortisol concentrations, despite a paucity
      of published validity data of these tests compared with the traditional 'gold
      standard' radioimmunoassay. OBJECTIVES: To compare a commercial chemiluminescence
      assay with radioimmunoassay for blood cortisol measurement, determine the effect
      of storage on the radioimmunoassay, and determine the impact of any differences
      on clinical decisions. METHODS: The study included 54 client owned dogs
      undergoing adrenal function testing. Fresh plasma or serum samples (n=170) were
      assayed for cortisol using radioimmunoassay (RIA1). Samples (n=196) were also
      frozen and stored in batches, and assayed by chemiluminescence and
      radioimmunoassay (RIA2). RESULTS: Overall, there was a strong correlation
      (r2=0.967, P<0.001) between RIA2 and chemiluminescence concentrations without
      significant difference between means. Strong correlations were present for RIA2
      and chemiluminescence at concentration subgroups of >400 nmol/L (r2=0.869,
      P<0.001), <100 nmol/L (r2=0.790, P<0.001), and <40 nmol/L (r2=0.738, P<0.001).
      Significant differences between means were present for RIA2 and chemiluminescence
      concentrations in the <100 nmol/L, and <40 nmol/L (P<0.001) groups. Despite a
      significant difference in RIA1 and RIA2 results overall, there was no significant
      difference between RIA1 and RIA2 for any of the concentration groups. In seven
      cases, discrepant RIA2 and chemiluminescence results may have altered clinical
      decisions. CONCLUSIONS: Although RIA and chemiluminescence cortisol
      concentrations appear highly correlated, a significant difference may exist for
      concentrations less than 100 nmol/L in stored canine sera. Results of
      chemiluminescence cortisol assays should be interpreted with caution unless the
      specific assay method in the laboratory has been adequately validated in dogs.

PMID- 18042156
TI  - Recovery of a dog from aplastic anaemia after treatment with mycophenolate
      mofetil.

PMID- 18042157
TI  - Salmonella and on-farm risk factors in healthy slaughter-age cattle and sheep in
      eastern Australia.
AB  - OBJECTIVE: To examine healthy slaughter-age cattle and sheep on-farm for the
      excretion of Salmonella serovars in faeces and to identify possible risk factors
      using a questionnaire. PROCEDURE: The study involved 215 herds and flocks in the
      four eastern states of Australia, 56 with prior history of salmonellosis.
      Production systems examined included pasture beef cattle, feedlot beef cattle,
      dairy cattle, prime lambs and mutton sheep and animals were all at slaughter age.
      From each herd or flock, 25 animals were sampled and the samples pooled for
      Salmonella culture. All Salmonella isolated were serotyped and any Salmonella
      Typhimurium isolates were phage typed. Questionnaires on each production system,
      prepared in Epi Info 6.04, were designed to identify risk factors associated with
      Salmonella spp excretion, with separate questionnaires designed for each
      production system. RESULTS: Salmonellae were identified in all production systems
      and were more commonly isolated from dairies and beef feedlots than other
      systems. Statistical analysis revealed that dairy cattle were significantly more
      likely to shed Salmonella in faeces than pasture beef cattle, mutton sheep and
      prime lambs (P<0.05). A wide diversity of Salmonella serovars, all of which have
      been isolated from humans in Australia, was identified in both cattle and sheep.
      Analysis of the questionnaires showed access to new arrivals was a significant
      risk factor for Salmonella excretion on dairy properties. For beef feedlots, the
      presence of large numbers of flies in the feedlot pens or around stored manure
      were significant risk factors for Salmonella excretion. CONCLUSION: Dairy cattle
      pose the highest risk of all the slaughter-age animals tested. Some of the
      identified risk factors can be overcome by improved management practices,
      especially in relation to hygiene.

PMID- 18042158
TI  - Minimal inhibitory concentration of tilmicosin against isolates of Histophilus
      somni from Australian cattle.

PMID- 18042160
TI  - Cyanide poisoning in cattle from Dysphania glomulifera (red crumbweed): using the
      internet for rapid plant identification and diagnostic advice.
AB  - A 300-strong Angus-Brahman cattle herd near Springsure, central Queensland, was
      being fed Acacia shirleyi (lancewood) browse during drought and crossed a 5
      hectare, previously burnt area with an almost pure growth of Dysphania
      glomulifera subspecies glomulifera (red crumbweed) on their way to drinking
      water. Forty cows died of cyanide poisoning over 2 days before further access to
      the plant was prevented. A digital image of a plant specimen made on a flat-bed
      scanner and transmitted by email was used to identify D glomulifera. Specific
      advice on the plant's poisonous properties and management of the case was then
      provided by email within 2 hours of an initial telephone call by the field
      veterinarian to the laboratory some 600 km away. The conventional method using
      physical transport of a pressed dried plant specimen to confirm the
      identification took 5 days. D glomulifera was identified in the rumen of one of
      two cows necropsied. The cyanogenic potential of D glomulifera measured 4 days
      after collection from the site of cattle deaths was 18,600 mg HCN/kg in dry
      matter. The lethal dose of D glomulifera for a 420 kg cow was estimated as 150 to
      190 g wet weight. The plant also contained 4.8% KNO3 equivalent in dry matter,
      but nitrate-nitrite poisoning was not involved in the deaths.

PMID- 18042161
TI  - Inguinal and axillary dermatitis in wallabies in north Queensland due to the
      dermanyssid mite Thadeua serrata.

PMID- 18042162
TI  - The end of veterinary homeopathy.

PMID- 18042163
TI  - Treatment of a metallic foreign body in the cranial cervical region of a horse.
AB  - Ingestion of foreign bodies is uncommon in horses when compared with
      indiscriminate grazers such as cattle. This case report describes the diagnosis
      and treatment of a cervical abscess in a Thoroughbred racehorse thought to be
      associated with ingestion of wire. Radiographic and ultrasonographic examination
      provided a diagnosis, and conservative treatment of the lesion with
      antimicrobials initially allowed the lesion to localise closer to the skin for
      safer surgical exploration. Intra-operative ultrasonographic imaging facilitated
      surgical access, removal of the foreign body, and drainage. While surgical
      treatment is usually necessary to resolve an abscess, initially conservative
      therapy may help to improve the prognosis by simplifying surgical access and
      reducing the risk of surgical complications.

PMID- 18042164
TI  - Equine influenza: an update.

PMID- 18042165
TI  - Abstracts of the Australasian Society of Clinical Immunology & Allergy (ASCIA)
      18th Annual Scientific Meeting, 14-16 November 2007, Fremantle, Western
      Australia.

PMID- 18042166
TI  - Mexican immunoparasitology: what is done and has to be done.
AB  - In this special issue of Parasite Immunology, the reader will find reviewed some
      of the hottest topics in immunoparasitology, with emphasis on the most studied
      parasite species in Mexico. For instance, the immunological conditions that
      appear favorable for the survival or destruction of the parasite in the
      intermediate and definitive hosts in cysticercosis, as well as the use of
      immunodiagnostic tests in epidemiological/intervention studies are discussed in
      two different articles. The role that alternatively activated macrophages plays
      in modulating host immunity is also discussed, while in the field of
      Leishmaniasis, the reader will find reviewed the role that CD8+ T cells play in
      the host defense during the human infection. The role that antibodies may play as
      biomarkers of protective or pathological cellular immune events in Toxoplasma
      gondii infections, as well as the new insights about the regulation of the
      inflammatory immune response by the cytokine/chemokine network in amebiasis, are
      topics reviewed. The use that TSL-1 antigens may have in the development of more
      sensitive and specific diagnosis of human and animal trichinellosis as well as
      the role that the neuroimmunoendocrine network plays during schistosomiasis are
      also presented. We hope that our readers will find fascinating and enticing, the
      first ever Special Issue devoted to Mexican Immunoparasitology.

PMID- 18042167
TI  - The host-parasite neuroimmunoendocrine network in schistosomiasis: consequences
      to the host and the parasite.
AB  - The physiological interactions during the course of any immune response are
      complex. Infection induces antigen-specific recognition by the immune system,
      which is consequently charged with the responsibility of marshalling the
      appropriate effector responses necessary to destroy the pathogen, or at the very
      least inhibit its progression. Obviously, the immune system should accomplish
      this while minimizing collateral damage to the host or it risks, winning a
      Pyrrhic victory. As our understanding of the neuroendocrine system grows, it has
      become increasingly clear that this complex network of neurotransmitters,
      hormones and cytokines plays an important role in mediating immunity.
      Schistosomes present an especially complex relationship between pathogen and
      these physiological systems, with hormonally dependent host factors such as sex
      and age correlated with parasite success. In this report, we review the current
      literature on sex and age associations between infection and progression of
      disease. We then follow with a discussion on interactions between the host
      neuroendocrine and immune systems. We also speculate on strategies to apply this
      knowledge to novel treatment strategies. Results argue for a complex network
      comprising the immune, endocrinological and nervous systems of both host and
      schistosome in the regulation of the plural outcomes of infection.

PMID- 18042168
TI  - The divergent roles of alternatively activated macrophages in helminthic
      infections.
AB  - Macrophages play crucial roles in the immune response, as they can initiate,
      modulate and also be final effector cells during immune responses to infections.
      Macrophages are derived from myeloid precursor cells in bone marrow and are
      widely distributed in every tissue of the body. Over the past 10 years, the
      concepts about macrophage activation have clearly changed; macrophages are not
      called activated or inactivated as they used to be. These changes in the concept
      of macrophage response is the result of many in vitro and in vivo studies, but
      the major support for the current concept of alternatively activated macrophages
      (AAMphi) comes from parasitic helminth infections. Parasitic helminths have
      developed complex mechanisms to evade and modulate host immunity. Infections with
      these parasites induce strong polarized Th2-type immune responses frequently
      associated with impaired T-cell proliferative responses to parasitic or unrelated
      antigens. Given the recent advances in understanding the immunoregulatory
      capabilities of helminthic infections, it has been suggested that macrophages can
      be a target for immunomodulation. Furthermore, they become altered when a host
      experiences chronic exposure to helminth parasites or their by-products, which
      favour the induction of AAMphi. How AAMphi participate in modulating host
      immunity during helminth infections and what their roles are in clearing or
      favouring parasite survival remains elusive. Here we review the most recent
      advances in the literature on AAMphi at the host-parasite interface, including
      three classes of helminths: nematodes (Brugia, Nippostrongylus, Litomosoides,
      Heligmosomoides), trematodes (Schistosoma, Fasciola) and cestodes (Taenia,
      Echinococcus, Hymenolepis).

PMID- 18042169
TI  - The immune response in Taenia solium cysticercosis: protection and injury.
AB  - This article reviews current knowledge on the innate and acquired immune
      responses in human Taenia solium neurocysticercosis, highlighting the conditions
      that appear to be favourable for the survival or destruction of the parasite and
      for the benefit or injury to its host.

PMID- 18042170
TI  - Contribution of immunodiagnostic tests to epidemiological/intervention studies of
      cysticercosis/taeniosis in Mexico.
AB  - Cysticercosis is acquired when swine ingest human faeces contaminated with Taenia
      solium eggs. Humans become tapeworm carriers when they ingest infected pork meat.
      They can also develop cysticercosis after inadvertently swallowing T. solium
      eggs. Human neurocysticercosis (NCC) is considered as a public health problem in
      Mexico and in several countries around the world, mainly developing ones. The
      development of immunodiagnostic techniques has promoted the conduct of
      seroepidemiological studies. This review provides insight into the evolution of
      these techniques, their predictive values and their use in field studies, and
      summarizes evidence supporting health care practice and policy related to
      cysticercosis/taeniosis in Mexico. Serological studies in rural and urban
      settings have demonstrated that close proximity with a tapeworm carrier is the
      main risk factor for acquiring cysticercosis. Research focusing on the tapeworm
      carrier generated an ELISA for the detection of Taenia coproantigens and
      facilitated the evaluation of intervention measures. Health education and self
      identification of tapeworm carriers were shown to be successful. However,
      cestodial treatment as a community-based intervention was not as successful.
      Current immunodiagnostic techniques can be used to pinpoint transmission foci so
      that appropriate and effective interventions can be applied. In this way,
      sustainable control, and even eradication of T. solium may be envisioned.

PMID- 18042171
TI  - Congenital and acquired toxoplasmosis: diversity and role of antibodies in
      different compartments of the host.
AB  - The apicomplexan parasite Toxoplasma gondii is remarkable in several aspects,
      since it is a protozoan that infects most nucleated cells in many warm-blooded
      animals, worldwide. Although the cellular immune response against T. gondii is
      critical for infection control, antibodies may either enhance or block protective
      mechanisms, and even mediate immunological damage, directly or indirectly. Since
      cytokines regulate the class/subclass switch, antibodies may also be the
      biomarkers of protective or pathological cellular immune events. There is a
      scientific and clinical interest in the presence of natural and autoreactive
      antibodies, as well as in the 'chronic' immunoglobulin M (IgM) response and the
      post-treatment 'rebound'. Another interesting aspect is compartmentalization;
      certain immunoglobulins may uniquely be found in specific host fluids. Local
      synthesis has been demonstrated, but antibodies may also traverse several cell
      layers, like the blood-brain and haemato-ocular barriers, and the placenta. In
      some instances, Fc receptors (FcRs) facilitate transport and may even have a
      concentrator effect, which can be related to resistance or pathology. These
      aspects of the humoral response against T. gondii are reviewed in the present
      paper.

PMID- 18042172
TI  - Contributions to the study of Trichinella spiralis TSL-1 antigens in host
      immunity.
AB  - The observation on different hosts infected with Trichinella spiralis that
      recognized similar muscle larvae (ML) antigens and the fact that different
      monoclonal antibodies (mAb) had a similar reactivity to ML components prompted a
      proposal to define a useful classification system for these antigens. For this
      purpose, an international workshop provided a platform for the classification of
      T. spiralis antigens. ML antigens were classified in eight groups -- Trichinella
      spiralis larvae groups, TSL-1 to TSL-8. TSL-1 antigens are highly immunogenic and
      a number of important studies have been performed to analyse the role of these
      antigens in the host-parasite interplay. In this context, we have focused on the
      analysis of the role of TSL-1 antigens in the induction of innate immune
      responses with particular emphasis on the activation of mast cells (MC) by an IgE
      independent pathway. These studies provided evidence on the role of mediator
      release from TSL-1-activated MC in the development of Type 2 immune responses.
      The protective role of TSL-1 in T. spiralis-infected mice has been described. In
      addition, it has been demonstrated that the use of TSL-1 antigens allows for a
      more sensitive and specific diagnosis of human and animal trichinellosis.

PMID- 18042173
TI  - CD8 cytotoxic T cells in cutaneous leishmaniasis.
AB  - CD8 T cells are essential in the defence against viruses, yet little is known of
      their participation in the host defence against parasites, such as Leishmania,
      which can cause a variety of clinical diseases, such as localized cutaneous,
      diffuse cutaneous, mucocutaneous and visceral leishmaniasis. Murine models of
      leishmaniasis suggest that CD8 T cells participate through IFN-gamma production,
      yet their cytotoxic capacity also plays an important role, as has been found in
      patients infected with various Leishmania strains, where CD8 T cell cytotoxicity
      and apoptosis of autologous Leishmania-infected macrophages correlate with cure.
      Yet the mechanisms underlying the CD8 T activation in patients with leishmaniasis
      remain an enigma. It is possible that dendritic cells activate CD8 T cells
      through mechanisms that include antigen cross-presentation. Here we summarize the
      recent findings of CD8 T cells in cutaneous leishmaniasis and discuss their
      significance in the control of the disease. Further knowledge in this field will
      undoubtedly improve the design of therapeutic and vaccine strategies.

PMID- 18042174
TI  - Regulation of the inflammatory immune response by the cytokine/chemokine network
      in amoebiasis.
AB  - Amoebiasis is caused by the protozoa Entamoeba histolytica and persists as one of
      the leading parasitic diseases affecting millions worldwide. This parasite
      invades the intestinal mucosa, causing amoebic colitis and ulcers. It may also
      spread to other organs, mainly the liver, causing amoebic liver abscess (ALA).
      Current research efforts have focused on the development of specific diagnostic
      tests and animal models searching for a better understanding of the complex
      physiopathology of this disease. Analysis of the inflammatory immune response
      during intestinal amoebiasis in both human disease and animal murine models has
      revealed an important regulatory role for chemokines and cytokines. Recruitment
      and activation of inflammatory cells can also be modulated by specific protease
      mediated cleavage of cytokines and by secreted amoebic factors such as
      amoebapores and monocyte locomotion inhibitory factor (MLIF). Unlike intestinal
      amoebiasis, analysis of the immune response in ALA has mainly been done in the
      hamster model. This has limited our information regarding the immune response
      during this phase of the disease. However, even with these limitations, several
      Th1/2 cytokines, such as IL-6 and IL-4, and regulatory cytokines, like IL-10 and
      TGFbeta, have been associated to the development of this disease.

PMID- 18042175
TI  - Conventional withdrawal of thyroid hormone before radioiodine therapy in
      differentiated thyroid carcinoma: how frequently are adequately raised TSH levels
      attained?

PMID- 18042176
TI  - Influence of iodine on the reference interval of TSH and the optimal interval of
      TSH: results of a follow-up study in areas with different iodine intakes.
AB  - OBJECTIVE: The aim of the present study was to evaluate whether the status of
      iodine nutrition influences the TSH concentration in a selected Chinese reference
      population according to the criteria proposed by National Academy of Clinical
      Biochemistry (NACB) and regular thyroid ultrasonography, to establish a new
      reference interval of TSH based on the wide variation of iodine nutrition in
      populations, and to identify an optimal interval of TSH by following up the
      cohort with normal TSH concentrations at baseline. DESIGN: The study was
      conducted in Panshan, Zhangwu and Huanghua, the regions with mildly deficient,
      more than adequate and excessive iodine intake, respectively. Of the 3761
      unselected subjects who were enrolled at baseline, 2237 met the criteria for a
      reference population. Of 3048 subjects with normal serum TSH at baseline, 2727
      (80.0%) participated in the 5-year follow-up study. TSH and thyroid
      autoantibodies in serum and iodine in urine were measured, and B-mode
      ultrasonography of the thyroid was performed. RESULTS: In the reference
      population, there was a urinary iodine-related increment of serum TSH levels (r =
      0.21, P = 0.000), and the mean levels of TSH in Panshan, Zhangwu and Huanghua
      were 1.15, 1.28 and 1.93 mIU/l, respectively (P = 0.000), corresponding to the
      rising regional iodine intake. Based on the overall data, we obtained a reference
      interval of 0.3-4.8 mIU/l. TSH concentrations obtained in the follow-up study
      correlated well with those at baseline (r = 0.58, P = 0.000). A baseline serum
      TSH > 1.9 mIU/l was associated with an increased incidence of development of
      supranormal TSH and a baseline serum TSH < 1.0 mIU/l was associated with an
      increased incidence of subnormal TSH development. CONCLUSIONS: Iodine nutrition
      is an important factor associated with TSH concentration even in the rigorously
      selected reference population. Baseline TSH of 1.0-1.9 mIU/l is an optimal
      interval with the lowest incidence of abnormal TSH in 5 years.

PMID- 18042177
TI  - Age-related decrease in stimulated glutamate release and vesicular glutamate
      transporters in APP/PS1 transgenic and wild-type mice.
AB  - We assessed baseline and KCl-stimulated glutamate release by using microdialysis
      in freely moving young adult (7 months) and middle-aged (17 months) transgenic
      mice carrying mutated human amyloid precursor protein and presenilin genes (APdE9
      mice) and their wild-type littermates. In addition, we assessed the age-related
      development of amyloid pathology and spatial memory impaired in the water maze
      and changes in glutamate transporters. APdE9 mice showed gradual spatial memory
      impairment between 6 and 15 months of age. The stimulated glutamate release
      declined very robustly in 17-month-old APdE9 mice as compared to 7-month-old
      APdE9 mice. This age-dependent decrease in stimulated glutamate release was also
      evident in wild-type mice, although it was not as robust as in APdE9 mice. When
      compared to individual baselines, all aged wild-type mice showed 25% or greater
      increase in glutamate release upon KCl stimulation, but none of the aged APdE9
      mice. There was an age-dependent decline in VGLUT1 levels, but not in the levels
      of VGLUT2, GLT-1 or synaptophysin. Astrocyte activation as measured by glial
      acidic fibrillary protein was increased in middle-aged APdE9 mice. Blunted pre
      synaptic glutamate response may contribute to memory deficit in middle-aged APdE9
      mice.

PMID- 18042178
TI  - Preferential vulnerability of mesencephalic dopamine neurons to glutamate
      transporter dysfunction.
AB  - Nigral depletion of the main brain antioxidant GSH is the earliest biochemical
      event involved in Parkinson's disease pathogenesis. Its causes are completely
      unknown but increasing number of evidence suggests that glutamate transporters
      [excitatory amino acid transporters (EAATs)] are the main route by which GSH
      precursors may enter the cell. In this study, we report that dopamine (DA)
      neurons, which express the excitatory amino acid carrier 1, are preferentially
      affected by EAAT dysfunction when compared with non-DA neurons. In rat embryonic
      mesencephalic cultures, l-trans-pyrrolidine-2,4-dicarboxylate, a substrate
      inhibitor of EAATs, is directly and preferentially toxic for DA neurons by
      decreasing the availability of GSH precursors and lowering their resistance
      threshold to glutamate excitotoxicity through NMDA-receptors. In adult rat, acute
      intranigral injection of l-trans-pyrrolidine-2,4-dicarboxylate induces a large
      regionally selective and dose-dependent loss of DA neurons and alpha-synuclein
      aggregate formation. These data highlight for the first time the importance of
      excitatory amino acid carrier 1 function for the maintenance of antioxidant
      defense in DA neurons and suggest its dysfunction as a candidate mechanism for
      the selective death of DA neurons such as occurring in Parkinson's disease.

PMID- 18042180
TI  - Hypergonadotropic hypogonadism in a patient with inv ins (2;4).
AB  - We report on a 30-year-old man with azoospermia, primary hypogonadism and minor
      dysmorphic features who carried a balanced insertional chromosome translocation
      inv ins (2p24;4q28.3q31.22)de novo. Molecular cytogenetic analyses of the
      chromosome breakpoints revealed the localization of the breakpoint in 4q28.3
      between BACs RP11-143E9 and RP11-285A15, an interval that harbours the PCDH10
      gene. In 4q31.22, a breakpoint-spanning clone (RP11-6L6) was identified which
      contains the genes LSM6 and SLC10A7. On chromosome 2, BACs RP11-531P14 and RP11
      360O18 flank the breakpoint in 2p24, a region void of known genes. In conclusion,
      the chromosome aberration of this patient suggests a gene locus for primary
      hypogonadism in 2p24, 4q28.3 or 4q31.2, and three possible candidate genes (LSM6,
      SLC10A7 and PCDH10) were identified by breakpoint analyses.

PMID- 18042179
TI  - Genetic or pharmacological blockade of noradrenaline synthesis enhances the
      neurochemical, behavioral, and neurotoxic effects of methamphetamine.
AB  - N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesions of the locus
      coeruleus, the major brain noradrenergic nucleus, exacerbate the damage to
      nigrostriatal dopamine (DA) terminals caused by the psychostimulant
      methamphetamine (METH). However, because noradrenergic terminals contain other
      neuromodulators and the noradrenaline (NA) transporter, which may act as a
      neuroprotective buffer, it was unclear whether this enhancement of METH
      neurotoxicity was caused by the loss of noradrenergic innervation or the loss of
      NA itself. We addressed the specific role of NA by comparing the effects of METH
      in mice with noradrenergic lesions (DSP-4) and those with intact noradrenergic
      terminals but specifically lacking NA (genetic or acute pharmacological blockade
      of the NA biosynthetic enzyme dopamine beta-hydroxylase; DBH). We found that
      genetic deletion of DBH (DBH-/- mice) and acute treatment of wild-type mice with
      a DBH inhibitor (fusaric acid) recapitulated the effects of DSP-4 lesions on METH
      responses. All three methods of NA depletion enhanced striatal DA release,
      extracellular oxidative stress (as measured by in vivo microdialysis of DA and
      2,3-dihydroxybenzoic acid), and behavioral stereotypies following repeated METH
      administration. These effects accompanied a worsening of the striatal DA neuron
      terminal damage and ultrastructural changes to medium spiny neurons. We conclude
      that NA itself is neuroprotective and plays a fundamental role in the sensitivity
      of striatal DA terminals to the neurochemical, behavioral, and neurotoxic effects
      of METH.

PMID- 18042181
TI  - FSH and bFGF stimulate the production of glutathione in cultured rat Sertoli
      cells.
AB  - Migration of developing germ cells from the basal to the adluminal compartment of
      the seminiferous epithelium requires extensive tissue restructuring, resulting in
      the production of reactive oxygen species. Sertoli cells are involved in this
      process. Glutathione (GSH), produced by Sertoli cells, has an essential role in
      cell protection against oxidative stress. Intracellular GSH content is maintained
      by de novo synthesis, involving glutamate-cysteine ligase catalytic (GCLC) and
      modulatory (GCLM) subunits, and by recycling from oxidized GSH, catalysed by
      glutathione reductase (GR). To assess whether follicle-stimulating hormone (FSH)
      and basic fibroblast growth factor (bFGF) modulate GSH production in Sertoli
      cells by regulating the expression of GCLC, GCLM and/or GR, we performed in vitro
      studies using rat Sertoli cells in primary culture. FSH and bFGF stimulation
      increased Sertoli cell GSH levels after 24 h incubation. The simultaneous
      addition of FSH and bFGF did not produce any further effect. GCLM expression was
      upregulated by FSH and bFGF 6 h. At 24 h, only the FSH-mediated effect was still
      observed. FSH and bFGF also upregulated GR expression. In conclusion, our results
      show that FSH and bFGF increase GSH levels in Sertoli cells through stimulation
      of the de novo synthesis and recycling by upregulating GCLM and GR expression
      respectively. Therefore, protection of germ cells against oxidative stress seems
      to be regulated by hormones and germ cell-released growth factors capable of
      influencing the production of Sertoli cell GSH.

PMID- 18042182
TI  - Androgen receptor CAG repeats and body composition among Ariaal men.
AB  - To determine the population variation in the androgen receptor (AR) and its
      association with body composition in a subsistence population, we sampled 87
      settled and 65 nomadic males ages 20+ among the Ariaal of northern Kenya.
      Anthropometric measures included height, body mass index, fat-free mass (FFM),
      upper arm muscle plus bone area (AMPBA), % body fat (%BF), suprailliac skinfold
      (SISF), and waist-to-hip ratio. Salivary testosterone (T) was determined from
      both morning (Am T) and afternoon (Pm T) samples. Hair roots were obtained for
      genotyping AR CAG repeat length. AR CAG repeat length did not vary between the
      two sub-groups (overall value = 22.6 +/- 3.1). Multiple regression models,
      controlling for age and residence, indicate that Pm T was positively associated
      with all measures of body composition. AR CAG repeat length was a significant
      positive predictor of height, FFM, %BF, SISF and waist circumference. There was a
      significant negative Pm T by AR CAG repeat length interaction in predicting all
      anthropometric measures but AMPBA. These findings provide evidence for population
      variation in AR CAG repeat length and suggest that both T and AR CAG length play
      a role in body composition in this extremely lean population.

PMID- 18042183
TI  - Approaches to medical student remediation after a comprehensive clinical skills
      examination.
AB  - OBJECTIVE: Most US medical schools conduct comprehensive clinical skills
      assessments during Years 3 and 4. This study explores strategies used to identify
      and remediate students who perform poorly on these assessments. METHODS: In the
      academic year 2005-06, we conducted 33 semi-structured interviews with
      individuals responsible for standard setting in and remediation after their
      schools' comprehensive clinical skills assessments. We coded interviews to
      identify major themes. RESULTS: Prior to remediation, some schools employed a
      'verification' step to ensure the accuracy of the failing score or need for
      remediation. Participants described a remediation process that included some or
      all of 3 steps. Firstly, students' specific learning deficits were diagnosed.
      Next, students participated in remedial activities such as performance review
      sessions or practice with standardised or actual patients. Lastly, students were
      re-tested, usually with a shorter, more formative examination. All participants
      reported using a diagnostic step, most offered or required remedial activities
      and many re-tested, although schools varied in the emphasis placed on each step.
      Many participants cited the individualised attention students received from
      remediation faculty staff as a strength of their approach, although they raised
      concerns about the substantial time demands placed on remediation faculty. Most
      respondents reported some dissatisfaction with their school's remediation
      process, particularly uncertainty about efficacy or rigour. CONCLUSIONS: Schools
      vary in the intensity and scope of remediation offered to students who perform
      poorly on clinical skills assessments. Although many schools invest significant
      resources in remediation, the effect of these efforts on students' subsequent
      clinical performance is unknown.

PMID- 18042184
TI  - What does patient-centred communication mean in Nepal?
AB  - OBJECTIVES: To ascertain the expectations of Nepalese patients regarding aspects
      of doctor-patient communication and to review a model of patient-centred care for
      its appropriateness to Nepalese medical communication training. METHODS: A cross
      sectional survey, using an adapted version of the Patient-Practitioner
      Orientation Scale (PPOS), was undertaken with a random sample of patients
      attending a general outpatients department in rural Nepal. An alternative survey
      instrument, derived from the PPOS, was also used. RESULTS: The following issues
      were most important to patients: being treated in a friendly and respectful
      manner; being fully informed, and being given adequate consultation time.
      Patients were happy for the doctor to be in charge and did not want to seek
      information outside the doctor's advice. They expressed a strong preference for
      receiving advice about preventative care. Patient responses were significantly
      more 'doctor-centred' than those found in comparable studies in the USA.
      DISCUSSION: Patients expressed strong preferences for some aspects of patient
      centred communication (PCC), but were not very concerned with sharing power and
      control. Models of PCC in Nepal require modification to reflect these local
      preferences. The importance of good communication techniques requires emphasis in
      clinical training and practice. Methods of disseminating information need to be
      enhanced in this low-literacy setting.

PMID- 18042185
TI  - Germination and conjugation of Bacillus thuringiensis subsp. israelensis in the
      intestine of gnotobiotic rats.
AB  - AIMS: To study the ability of Bacillus thuringiensis subsp. israelensis spores to
      germinate and subsequently transfer a conjugative plasmid in the intestinal tract
      of gnotobiotic rats. METHODS AND RESULTS: Germination was studied by feeding germ
      free rats with spores of a B. thuringiensis strain harbouring a plasmid encoding
      green fluorescent protein (GFP), which enabled quantification of germinated
      bacteria by flow cytometry. To study in vivo conjugation, germ-free rats were
      first associated with a B. thuringiensis recipient strain and after 1 week an
      isogenic donor strain harbouring the conjugative plasmid pXO16 was introduced.
      Both strains were given as spores and transfer of pXO16 was observed from the
      donor to the recipient strain. CONCLUSIONS: Bacillus thuringiensis is able to
      have a full life cycle in the intestine of gnotobiotic rats including germination
      of spores, several cycles of growth and sporulation of vegetative cells. For the
      first time conjugative plasmid transfer in a mammalian intestinal tract was shown
      between two B. thuringiensis strains. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Strains of B. thuringiensis are used worldwide to combat insect pests, and this
      study brings new insights into the nature of B. thuringiensis showing the
      potential of the bacteria to germinate and transfer DNA in the mammalian
      intestinal tract.

PMID- 18042186
TI  - Isolation of a homocysteine gamma-lyase-producing bacterium and study of its
      enzyme production conditions.
AB  - AIM: To investigate the possibility of finding a new homocysteine (Hcy) gamma
      lyase with the desired properties for Hcy measurement in bacteria. METHODS AND
      RESULTS: Through a process of enrichment, the Hcy gamma-lyase-producing bacterium
      strain N2-1 was isolated from soil. Based upon its morphological, physiological,
      and biochemical characteristics, as well as its 16S rDNA sequence and
      phylogenetic tree analysis, this isolate belongs to the genus Serratia. The
      effects of pH, aeration, inducers, carbon (C) and nitrogen (N) sources on enzyme
      production were studied. Methionine, yeast extract, and glucose were selected as
      the optimal inducer, C and N sources, respectively. Maximum production of Hcy
      gamma-lyase was obtained when the isolate was cultured at 30 degrees C at pH 6.5
      for about 36 h in the optimum medium. Results also showed that this Hcy gamma
      lyase has relatively high specificity towards Hcy. CONCLUSIONS: Because of its
      high specificity for Hcy, this bacterial Hcy gamma-lyase has the potential
      application in Hcy determination. SIGNIFICANCE AND IMPACT OF THE STUDY: In
      addition to isolating a bacterium that produces Hcy gamma-lyase suitable for Hcy
      determination, this study also indicates that the bacterium could be a source for
      production of Hcy gamma-lyase for clinical applications.

PMID- 18042187
TI  - The use of copper and silver in carbon point-of-use filters for the suppression
      of Legionella throughput in domestic water systems.
AB  - AIMS: To evaluate throughput of seeded Legionella pneumophila bacteria in
      domestic point-of-use filters. METHODS AND RESULTS: The filters were challenged
      with tap water seeded with Leg. pneumophila. After multiple challenge events
      (4.25 x 10(11) CFU per filter), the levels of Legionella were lower in the
      effluent from the filter containing both copper and silver (mean 4.48 x 10(3) CFU
      ml(-1)) than in the effluent from the filter containing copper only (1.26 x 10(4)
      CFU ml(-1); P < 0.001). After a single challenge event of approx. 5 x 10(9) CFU
      L. pneumophila per filter, there was no significant difference between the levels
      of Legionella in the effluents from a carbon filter containing copper and a
      carbon filter with no metals (mean 6.87 x 10(2) and 6.89 x 10(2) CFU ml(-1),
      respectively; P = 0.985). CONCLUSIONS: Legionella was detected in filter effluent
      up to 6 weeks after being challenged, indicating that while filters may reduce
      the levels during an initial contamination event, the exposure is extended as the
      accumulated bacteria slough off over time. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study has provided an understanding of the response of Legionella to the use
      of silver and copper in domestic point-of-use carbon filters.

PMID- 18042188
TI  - Anti-infectious potential of beta-mercapto-ethanol treated baker's yeast in
      gnotobiotic Artemia challenge test.
AB  - AIM: To evaluate nutritional and anti-infectious characteristics of the
      chemically treated baker's yeast with 2-mercapto-ethanol (2ME) for
      gnotobiotically grown Artemia. METHODS AND RESULTS: A selection of isogenic yeast
      strains was treated with 2ME and fed to gnotobiotically grown Artemia. In the
      first experiment the effect of the chemical treatment on the yeast nutritional
      value was studied. In most cases, 2ME-treated yeast cells were better feed for
      Artemia than the untreated cells. In the second experiment, a small quantity of
      2ME-treated yeast cells was fed to Vibrio campbellii (VC) challenged Artemia. The
      2ME-treatment on some yeast strains (e.g. gas1, kre6 and chs3) significantly
      improved Artemia resistance against VC compared with the respective untreated
      yeast cells. CONCLUSION: Simple chemical treatment with 2ME could significantly
      improve the nutritional and anti-infectious properties of some baker's yeast
      strains for gnotobiotically grown Artemia. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The gnotobiotic Artemia test system provides a unique opportunity (because of
      noninterference of other microbial compounds) to investigate how the yeast cell
      wall composition influences macro parameters (e.g. growth and survival) in an
      organism. In addition, gene expression studies in these gnotobiotically grown
      Artemia should provide further documentation on direct effects of yeast cells on
      the genes involved in immune functions.

PMID- 18042189
TI  - Reasons for migration among medical students from Karachi.
AB  - CONTEXT: The subject of economic migration among health care professionals has
      received intense attention. However, the aetiology of this migration has not been
      rigorously evaluated in Pakistan. Such knowledge can potentially influence health
      care and academic policies. Our current study proposes to quantify the relative
      contributions of various personal, professional and economic variables among
      final-year medical students in Karachi. METHODS: A self-administered structured
      questionnaire using a 10-point scale was developed and piloted among Karachi
      medical students. Additional open-ended questions were included to allow us to
      capture information not otherwise covered in the questionnaire. SPSS software was
      used for data entry and analysis. RESULTS: Over 95% of Aga Khan University (AKU)
      and over 65% of Baqai University (BU) final-year medical students intend to
      proceed abroad for their postgraduate training. The 2 most important factors
      behind this intent as pointed out by the students are poor salary structure (AKU
      mean score 8.94 +/- 1.73, BU mean score 7.14 +/- 2.6) and poor quality of
      training in the home country (AKU mean score 9.20 +/- 1.20, BU mean score 8.68 +/
      2.03). Other interesting factors captured through the open-ended questions were
      the poor work environment and lack of rigor in teaching of residents in domestic
      university hospitals. Over 50% of final-year medical students cited these issues
      as major reasons behind their decision to migrate.

PMID- 18042190
TI  - The effect of retail cigarette pack displays on impulse purchase.
AB  - AIMS: To assess the extent to which point-of purchase (POP) cigarette displays
      stimulate impulse purchases. DESIGN: Telephone-administered population survey.
      SETTING: Victoria, Australia. PARTICIPANTS: A total of 2996 adults, among whom
      526 smoked factory-made cigarettes and 67 were recent quitters (quit in the past
      12 months). MEASUREMENTS: Reported cigarette purchase behaviour; perceived effect
      on smoking of removing cigarettes from view in retail outlets; reported urges to
      buy cigarettes as a result of seeing the cigarette display. FINDINGS: When
      shopping for items other than cigarettes, 25.2% of smokers purchased cigarettes
      at least sometimes on impulse as a result of seeing the cigarette display. Thirty
      eight per cent of smokers who had tried to quit in the past 12 months and 33.9%
      of recent quitters experienced an urge to buy cigarettes as a result of seeing
      the retail cigarette display. One in five smokers trying to quit and one in eight
      recent quitters avoided stores where they usually bought cigarettes in case they
      might be tempted to purchase them. Many smokers (31.4%) thought the removal of
      cigarette displays from stores would make it easier for them to quit.
      CONCLUSIONS: POP cigarette displays act as cues to smoke, even among those not
      explicitly intending to buy cigarettes, and those trying to avoid smoking.
      Effective POP marketing restrictions should encompass cigarette displays.

PMID- 18042191
TI  - Addiction science and its genetics.
AB  - AIM: To assess the progress and impact of genetic studies in the addictions arena
      and to present this information in a form accessible to the general readership of
      Addiction. METHODS: Review of the evidence that genes are involved in addiction,
      approaches to their identification, current findings and the potential
      implications. RESULTS: Family, twin and adoption studies provide strong evidence
      that addiction runs in families and that this is determined in part by genetic
      factors. Two main molecular genetic approaches, namely linkage and association,
      have been adopted to identify the specific genes involved. Both methods are
      fraught with problems. Linkage is limited by issues of sensitivity, and
      association by false positives. Perhaps the strongest finding in psychiatric
      genetics to date is the impressive effect that a single genetic variant, in the
      aldehyde dehydrogenase 2 gene, has on drinking behaviour and reducing the risk of
      developing alcohol dependence. Other findings are currently less robust; however,
      the implications of elucidating the genetic underpinning of addiction will be
      profound. CONCLUSIONS: Addiction genetics is a developing science that has yet to
      prove its worth in the clinical setting.

PMID- 18042192
TI  - The role of spending money and drinking alcohol in adolescent smoking.
AB  - AIMS: Previous studies have shown inconsistent findings with regard to the
      association between amount of spending money and adolescent smoking. Drinking
      alcohol may be a mediator of the association between spending money and
      adolescent smoking. However, no studies have examined this potential role. The
      objective of this study was to investigate the association between amount of
      spending money and adolescent smoking and the potential mediation role of alcohol
      use in this association. DESIGN: The 2003 Ontario Student Drug Use Survey of
      students in grades 7-12. MEASUREMENTS: Multivariable logistic, probit and linear
      regression models were used to investigate the association between amount of
      spending money and smoking, and the contribution of drinking alcoholic beverages
      to this relationship. FINDINGS: Spending money was associated positively with
      experimental smoking, current smoking and daily consumption of cigarettes (P <
      0.01). The analysis adjusted for confounders showed that students with spending
      money > or =$20/week were significantly more likely to be experimental smokers,
      students with > or =$30/week were significantly more likely to be current smokers
      and students with > or =$60/week smoked significantly more cigarettes/day (P < or
      = 0.05), compared to students with <$10/week. Alcohol use was an important
      mediator, responsible for 81% of the association of spending money with
      experimental smoking, 38% with current smoking and 37% with daily consumption of
      cigarettes. CONCLUSIONS: Amount of spending money was associated significantly
      and positively with smoking among adolescents, and alcohol use mediated this
      association. Integrated tobacco prevention programs may be more effective, and
      increasing taxes on cigarettes and alcohol would increase price sensitivity among
      youth and protect against adolescent smoking.

PMID- 18042193
TI  - Risk, resilience, and natural recovery: a model of recovery from alcohol abuse
      for Alaska Natives.
AB  - AIM: The People Awakening (PA) study explored an Alaska Native (AN) understanding
      of the recovery process from alcohol abuse and consequent sobriety. DESIGN: PA
      utilized a cross-sectional, qualitative research design and community-based
      participatory research methods. SETTING AND PARTICIPANTS: The study included a
      state-wide convenience sample of 57 participants representing all five major AN
      groups: Aleut/Alutiiq, Athabascan, Inupiaq, Yup'ik/Cup'ik and
      Tlingit/Haida/Tsimshian. Participants were nominated and self-identified as being
      alcohol-abstinent at least five years following a period of problem drinking.
      MEASUREMENTS: Open-ended and semistructured interviews gathered extensive
      personal life histories. A team of university and community co-researchers
      analyzed narratives using grounded theory and consensual data analysis
      techniques. FINDINGS: A heuristic model of AN recovery derived from our
      participants' experiences describes recovery as a development process understood
      through five interrelated sequences: (i) the person entered into a reflective
      process of continually thinking over the consequences of his/her alcohol abuse;
      (ii) that led to periods of experimenting with sobriety, typically, but not
      always, followed by repeated cycling through return to drinking, thinking it
      over, and experimenting with sobriety; culminating in (iii) a turning point,
      marked by the final decision to become sober. Subsequently, participants engaged
      in (iv) Stage 1 sobriety, active coping with craving and urges to drink followed
      for some participants, but not all, by (v) Stage 2 sobriety, moving beyond coping
      to what one participant characterized as 'living life as it was meant to be
      lived. CONCLUSIONS: The PA heuristic model points to important cultural elements
      in AN conceptualizations of recovery.

PMID- 18042194
TI  - Gender and non-medical use of prescription opioids: results from a national US
      survey.
AB  - AIMS: Gender differences exist regarding alcohol and illicit drug use disorders
      in the United States. Little is known about the gender-related factors associated
      with non-medical use of prescription opioids. DESIGN: Using data from the 2003
      National Survey on Drug Use and Health, we examined risk factors for past-year
      non-medical use of prescription opioids stratified by gender. SETTING: Non
      institutionalized US residences. Participants Civilian, non-institutionalized US
      citizens aged 12 years and older. MEASUREMENTS: Self-reported alcohol and drug
      use, focusing specifically on past-year non-medical use of prescription opioids.
      FINDINGS: Among 55 023 respondents, 4.8% reported past-year, non-medical use of
      prescription opioids. For both women and men, alcohol abuse/dependence and
      marijuana, hallucinogen, cocaine, non-medical stimulant and sedative/tranquilizer
      use were associated with past-year non-medical use of prescription opioids. Among
      women but not men, first use of illicit drugs beginning at 24 years or older
      [adjusted odds ratios (AOR) 1.90, 95% CI 1.05-3.44], serious mental illness (AOR
      1.67, 95% CI 1.29-2.17) and cigarette smoking (AOR 1.33, 95% CI 1.05-1.68) were
      associated with past-year non-medical use of prescription opioids. Among men but
      not women, past-year inhalant use (AOR 1.93, 95% CI 1.28-2.92) was associated
      with the outcome. CONCLUSIONS: For both women and men, illicit drug use is
      associated with the non-medical use of prescription opioids. Additionally,
      certain factors associated with the non-medical use of prescription opioids are
      notably gender-specific. Clinicians should recognize that patients with a history
      of illicit substance use or misuse of other prescription medications are at
      increased risk for non-medical use of prescription opioids, and that gender
      specific factors can help to identify individuals at greatest risk.

PMID- 18042195
TI  - In-vitro activity and in-vivo efficacy of catheters impregnated with
      chloroxylenol and thymol against uropathogens.

PMID- 18042196
TI  - Candida glabrata fungaemia in intensive care units.
AB  - Candidaemia is increasingly important in intensive care units (ICUs). Compared
      with Candida albicans fungaemia, the impact of C. glabrata fungaemia on ICU
      patients is not well-known. The aim of this study was to investigate the clinical
      features, the antifungal susceptibility and the treatment outcomes of C. glabrata
      fungaemia in ICU patients. The medical records of ICU patients with candidaemia
      between 2000 and 2005 were reviewed retrospectively, and antifungal
      susceptibility testing was performed for isolates of C. glabrata. Among 147
      episodes of candidaemia occurring in adult ICUs, C. glabrata was the second most
      common species and accounted for 45 (30%) episodes of candidaemia. The incidence
      of C. glabrata fungaemia was 1.3/1000 ICU admissions. Fluconazole resistance was
      found in 11% of C. glabrata isolates. The 30-day all-cause mortality rate was
      58%. Therapeutic regimens containing amphotericin B were associated with better
      outcome. Despite higher fluconazole resistance, C. glabrata candidaemia was not
      associated with greater mortality than non-glabrata candidaemia in the ICU
      setting.

PMID- 18042197
TI  - The central role of the chemokine receptor, CXCR4, in haemopoietic stem cell
      transplantation: will CXCR4 antagonists contribute to the treatment of blood
      disorders?
AB  - Recent clinical trials have used CXCR4 antagonists for the rapid mobilization of
      CD34(+) haemopoietic stem/progenitor cells (HSC/HPC) from the bone marrow to the
      blood in patients refractory to granulocyte-colony-stimulating factor (G-CSF).
      These antagonists not only mobilize non-cycling cells with a higher proportion of
      repopulating cells, but also enhance CD34(+) cell mobilization when used in
      combination with G-CSF. Here, we review the importance of CXCR4 and its ligand
      CXCL12 in haemopoiesis, and the potential roles of CXCR4 antagonists in the
      clinical HSC transplant setting.

PMID- 18042198
TI  - Altered ecosystem carbon and nitrogen cycles by plant invasion: a meta-analysis.
AB  - Plant invasion potentially alters ecosystem carbon (C) and nitrogen (N) cycles.
      However, the overall direction and magnitude of such alterations are poorly
      quantified. Here, 94 experimental studies were synthesized, using a meta-analysis
      approach, to quantify the changes of 20 variables associated with C and N cycles,
      including their pools, fluxes, and other related parameters in response to plant
      invasion. Pool variables showed significant changes in invaded ecosystems
      relative to native ecosystems, ranging from a 5% increase in root carbon stock to
      a 133% increase in shoot C stock. Flux variables, such as above-ground net
      primary production and litter decomposition, increased by 50-120% in invaded
      ecosystems, compared with native ones. Plant N concentration, soil NH+4 and NO-3
      concentrations were 40, 30 and 17% higher in invaded than in native ecosystems,
      respectively. Increases in plant production and soil N availability indicate that
      there was positive feedback between plant invasion and C and N cycles in invaded
      ecosystems. Invasions by woody and N-fixing plants tended to have greater impacts
      on C and N cycles than those by herbaceous and nonN-fixing plants, respectively.
      The responses to plant invasion are not different among forests, grasslands, and
      wetlands. All of these changes suggest that plant invasion profoundly influences
      ecosystem processes.

PMID- 18042199
TI  - Inhibited polar auxin transport results in aberrant embryo development in Norway
      spruce.
AB  - Current hypotheses concerning the role of polar auxin transport in embryo
      development are entirely based on studies of angiosperms, while little is known
      about how auxin regulates pattern formation in gymnosperms. In this study,
      different developmental stages of somatic embryos of Norway spruce (Picea abies)
      were treated with the polar auxin transport inhibitor 1-N-naphtylphthalamic acid
      (NPA). Effects of the treatments on auxin content, embryo differentiation and
      programmed cell death (PCD) were analysed. During early embryo development, NPA
      treatment led to increased indole-3-acetic acid (IAA) content, abnormal cell
      divisions and decreased PCD, resulting in aberrant development of embryonal tube
      cells and suspensors. Mature embryos that had been treated with NPA showed both
      apical and basal abnormalities. Typically the embryos had abnormal cotyledon
      formation and irregular cell divisions in the area of the root meristem. Our
      results show that polar auxin transport is essential for the correct patterning
      of both apical and basal parts of conifer embryos throughout the whole
      developmental process. Furthermore, the aberrant morhologies of NPA-treated
      spruce embryos are comparable with several auxin response and transport mutants
      in Arabidopsis. This suggests that the role of polar auxin transport is conserved
      between angiosperms and gymnosperms.

PMID- 18042200
TI  - Whole-plant mineral partitioning throughout the life cycle in Arabidopsis
      thaliana ecotypes Columbia, Landsberg erecta, Cape Verde Islands, and the mutant
      line ysl1ysl3.
AB  - Minimal information exists on whole-plant dynamics of mineral flow through
      Arabidopsis thaliana or on the source tissues responsible for mineral export to
      developing seeds. Understanding these phenomena in a model plant could help in
      the development of nutritionally enhanced crop cultivars. A whole-plant
      partitioning study, using sequential harvests, was conducted to characterize
      growth and mineral concentrations and contents of rosettes, cauline leaves,
      stems, immature fruit, mature fruit hulls, and seeds of three WT lines (Col-0,
      Ler, and Cvi) and one mutant line (Col-0::ysl1ysl3). Shoot mineral content
      increased throughout the life cycle for all minerals, although tissue-specific
      mineral partitioning differed between genotypes. In particular, iron (Fe), zinc
      (Zn), and copper (Cu) were aberrantly distributed in ysl1ysl3. Remobilization was
      observed for several minerals from various tissues, including cauline leaves and
      silique hulls, but the amounts were generally far below the total mineral
      accretion observed in seeds. When YSL1 and YSL3 are nonfunctional, Cu, Fe, and Zn
      are not effectively remobilized from, or do not effectively pass through, leaf
      and maternal fruit tissues. With respect to seed mineral accretion in
      Arabidopsis, continued uptake and translocation of minerals to source tissues
      during seed fill are as important, if not more important, than remobilization of
      previously stored minerals.

PMID- 18042201
TI  - Small differences in arrival time influence composition and productivity of plant
      communities.
AB  - 'Who comes first' is decisive for plant community assembly and ecosystem
      properties. Early arrival or faster initial development of a species leads to
      space occupancy both above and below ground and contributes to species success.
      However, regular disturbance (e.g. biomass removal) might permit later-arriving
      or slower-developing species to catch up. Here, artificial communities of
      grassland species belonging to the plant functional types (PFTs) herb, grass and
      legume were used to test the effect of stepwise arrival (sowing) of PFTs.
      Dramatic effects were found as a result of a 3 wk arrival difference on
      composition and above-ground biomass that persisted over four harvests and two
      seasons. Priority effects, such as unequal germination time (arrival), and thus
      differences in community age structure, had lasting effects on PFT biomass
      contribution and associated ecosystem functioning. These effects were robust
      against above-ground disturbance. Benefits of earlier root formation outweighed
      above-ground species interaction. Earlier space occupancy and bigger reserve
      pools are the likely causes. Natural populations commonly exhibit age diversity
      and asynchrony of development among taxa. In experiments, artificial synchrony of
      arrival (sowing) may thus induce assembly routes favouring faster-establishing
      taxa, with consequences for ecosystem functioning (e.g. productivity). Founder
      effects, such as those observed here, could be even greater in communities of
      slow-growing species or forests, given their longer generation time and minor
      disturbance.

PMID- 18042202
TI  - Automatic discrimination of fine roots in minirhizotron images.
AB  - Minirhizotrons provide detailed information on the production, life history and
      mortality of fine roots. However, manual processing of minirhizotron images is
      time-consuming, limiting the number and size of experiments that can reasonably
      be analysed. Previously, an algorithm was developed to automatically detect and
      measure individual roots in minirhizotron images. Here, species-specific root
      classifiers were developed to discriminate detected roots from bright background
      artifacts. Classifiers were developed from training images of peach (Prunus
      persica), freeman maple (Acer x freemanii) and sweetbay magnolia (Magnolia
      virginiana) using the Adaboost algorithm. True- and false-positive rates for
      classifiers were estimated using receiver operating characteristic curves.
      Classifiers gave true positive rates of 89-94% and false positive rates of 3-7%
      when applied to nontraining images of the species for which they were developed.
      The application of a classifier trained on one species to images from another
      species resulted in little or no reduction in accuracy. These results suggest
      that a single root classifier can be used to distinguish roots from background
      objects across multiple minirhizotron experiments. By incorporating root
      detection and discrimination algorithms into an open-source minirhizotron image
      analysis application, many analysis tasks that are currently performed by hand
      can be automated.

PMID- 18042203
TI  - HAG2/MYB76 and HAG3/MYB29 exert a specific and coordinated control on the
      regulation of aliphatic glucosinolate biosynthesis in Arabidopsis thaliana.
AB  - In a previous transactivation screen, two Arabidopsis thaliana R2R3-MYB
      transcription factors, HAG2/MYB76 and HAG3/MYB29, along with the already
      characterized HAG1/MYB28, were identified as putative regulators of aliphatic
      glucosinolate biosynthesis. Molecular and biochemical characterization of
      HAG2/MYB76 and HAG3/MYB29 functions was performed using transformants with
      increased or repressed transcript levels. Real-time PCR assays, cotransformation
      assays and measurements of glucosinolate contents were used to assess the impact
      of both MYB factors on the steady-state level of glucosinolate biosynthetic genes
      and accumulation of aliphatic glucosinolates. Both HAG2/MYB76 and HAG3/MYB29 were
      shown to be positive regulators of aliphatic glucosinolate biosynthesis.
      Expression of promoter-beta-glucuronidase (GUS) fusions indicated GUS activities
      in both vegetative and generative organs, with distinct characteristics for each
      MYB factor. HAG1/MYB28, HAG2/MYB76 and HAG3/MYB29 reciprocally transactivated
      each other in the control of aliphatic glucosinolate biosynthesis and
      downregulated the expression of genes involved in the control of indolic
      glucosinolate biosynthesis, pointing to a reciprocal negative regulation of these
      two pathways. All three HAG transcription factors exert a coordinated control on
      aliphatic glucosinolate biosynthesis.

PMID- 18042204
TI  - Are there benefits of simultaneous root colonization by different arbuscular
      mycorrhizal fungi?
AB  - Arbuscular mycorrhizal fungal (AMF) communities were established in pots using
      fungal isolates from a single field in Switzerland. It was tested whether
      multispecies mixtures provided more phosphorus and supported greater plant growth
      than single AMF species. Two host plants, medic (Medicago truncatula) and leek
      (Allium porrum), were inoculated with three AMF species (Glomus mosseae, G.
      claroideum and G. intraradices), either separately or in mixtures. The
      composition of the AMF communities in the roots was assessed using real-time PCR
      to determine the copy number of large ribosomal subunit genes. Fungal communities
      in the roots were usually dominated by one AMF species (G. mosseae). The
      composition of the communities depended on both plant identity and the time of
      harvest. Leek colonized by a mixture of G. claroideum and G. intraradices
      acquired more P than with either of the two AMF separately. Direct evidence is
      provided for functional complementarity among species within the AMF community
      colonizing a single root system. Competition among the species poses a major
      challenge in interpreting experiments with mixed inoculations, but this is
      greatly facilitated by use of real-time PCR.

PMID- 18042205
TI  - Jasmonate signalling network in Arabidopsis thaliana: crucial regulatory nodes
      and new physiological scenarios.
AB  - Plant development and stress responses are regulated by complex signalling
      networks that mediate specific and dynamic plant responses upon activation by
      various types of exogenous and endogenous signal. In this review, we focus on the
      latest published work on jasmonate (JA) signalling components and new regulatory
      nodes in the transcriptional network that regulates a number of diverse plant
      responses to developmental and environmental cues. Not surprisingly, the majority
      of the key revelations in the field have been made in Arabidopsis thaliana.
      However, for comparative reasons, we integrate information on Arabidopsis with
      recent reports for other plant species (when available). Recent findings on the
      regulation of plant responses to pathogens by JAs, as well as new evidence
      implicating JAs in the regulation of senescence, suggest a common mechanism of JA
      action in these responses via distinct groups of transcription factors. Moreover,
      a significant increase in the amount of evidence has allowed placing of specific
      mitogen-activated protein kinases (MAPKs) as crucial regulatory nodes in the
      defence signalling network. In addition, we report on new physiological scenarios
      for JA signalling, such as organogenesis of nitrogen-fixing nodules and
      anticancer therapy.

PMID- 18042206
TI  - Effect of antibiotics in extender on bacterial and spermatozoal quality of cooled
      buffalo (Bubalus bubalis) bull semen.
AB  - The present study was designed to study the effect of traditional antibiotic
      combination (streptomycin and penicillin; SP) and relatively modern combination
      of antibiotics (gentamycin, tylosin, lincomycin and spectinomycin; GTLS) in
      extender on bacterial control and spermatozoal quality of liquid buffalo bull
      semen stored at 5 degrees C. Semen collected from Nili-Ravi buffalo bulls (n =
      10) was diluted with skim milk extender containing either SP (streptomycin 1000
      microg/ml and penicillin 1000 IU/ml), GTLS (gentamycin 500 microg/ml, tylosin 100
      microg/ml, lincomycin 300 microg/ml and spectinomycin 600 microg/ml) or negative
      control with no antibiotics (NA). Liquid semen was stored at 5 degrees C for 5
      days. Aerobic bacteria isolated from buffalo semen were Pseudomonas aeruginosa
      and Staphylococcus aureus. The only facultative anaerobic bacterium isolated was
      Klebsiella pneumoniae. In vitro antibiotic sensitivity test revealed that Ps.
      aeruginosa and Staph. aureus were susceptible to gentamycin. Staphylococcus
      aureus and K. pneumoniae were susceptible to tylosin and linco-spectinomycin.
      Total aerobic bacterial count was significantly lower in semen samples treated
      with GTLS than those of SP on third and fifth day of storage at 5 degrees C.
      There was no difference (p > 0.05) in sperm motility, longevity and plasma
      membrane integrity (PMI) in extender containing SP or GTLS combination until the
      third day of storage at 5 degrees C. On fifth day of storage sperm motility,
      longevity and PMI was significantly better in extender containing SP compared
      with GTLS and NA. Intact acrosomes, and sperm head, mid piece and tail
      abnormalities remained similar (p > 0.05) because of antibiotics up to 5 days of
      storage. In conclusion, GTLS is more capable than SP for bacterial control of
      buffalo bull semen. Moreover, GTLS and SP are equally efficient in preserving
      spermatozoal quality of extended buffalo bull semen for 3 days at 5 degrees C.

PMID- 18042207
TI  - Expression of vascular endothelial growth factor receptors in bovine cystic
      follicles.
AB  - Cystic follicles have excess fluid derived from blood flow in the theca interna
      of the follicle; therefore, the vasculature network is related to cystic follicle
      formation. Vascular endothelial growth factor (VEGF) is a potent stimulator of
      blood vessel permeability and angiogenesis. The aim of this study was to examine
      the expression of VEGF receptors proteins and mRNA in cystic follicles to
      elucidate the VEGF system in cystic follicles. The expression of protein for VEGF
      receptors; fms-like-tyrosine kinase-1 (Flt-1) and foetal liver kinase-1 (Flk-1)
      was detected by the immunohistochemical method. The mRNA expression of Flt-1 and
      Flk-1 in cystic follicles was determined by RT-PCR. Concentration of oestradiol
      17beta and progesterone in the follicular fluid of cystic follicles was
      determined using ELISA. Flt-1- and Flk-1 proteins were localized in granulosa and
      theca interna cells and endothelial cells of theca layers. The intensity of Flt-1
      and Flk-1 immunoreaction was similar among cystic follicles with various ratios
      of oestradiol-17beta/progesterone concentrations. The expression of Flt-1 and Flk
      1 mRNA was similar, regardless of the ratio of oestradiol-17beta to progesterone
      in follicular fluid. These results demonstrate that cystic follicles have both
      VEGF receptors in the granulosa and theca interna layers, which may be
      responsible for the increased permeability of microvessels, causing the
      accumulation of follicular fluid in cystic follicles.

PMID- 18042208
TI  - Effects of oxygen exposure and gentamicin on stallion semen stored at 5 and 15
      degrees C.
AB  - This study was undertaken to investigate the effects of storage of stallion semen
      in a defined milk protein extender at 5 and 15 degrees C under either anaerobic
      or aerobic conditions, with or without addition of the antibiotic gentamicin.
      Semen samples were collected from eight fertile stallions and stored for 96 h
      (day 0-4) and assessed daily for motility, velocity and membrane integrity
      (viability) using a CASA system. Samples for bacteriology assessment were taken
      on day 2 of storage. No significant (p > 0.05) differences in motility, velocity
      or viability were observed between treatments on days 0-2. On days 3 and 4, semen
      stored without gentamicin at 5 degrees C had a significantly (p < 0.05) better
      semen quality compared with storage at 15 degrees C without gentamicin,
      irrespective of oxygen exposure. On days 3 and 4, motility and velocity were
      greater in samples stored at 15 degrees C with gentamicin, compared with the
      corresponding treatments without antibiotic (p < 0.05). This effect was also
      evident for viability on day 4. The decline in semen quality observed at 15
      degrees C most likely resulted from the effect of bacterial growth. Bacterial
      growth was the greatest in samples stored at 15 degrees C without gentamicin,
      under both anaerobic and aerobic conditions (p < 0.05). Bacterial growth was
      inhibited by adding of gentamicin at 15 degrees C, which accordingly reduced the
      decline in semen quality. Addition of antibiotic to samples stored at 5 degrees C
      had no significant effect on any parameter analysed. In conclusion, storage at 15
      degrees C can be achieved by using an extender containing the antibiotic
      gentamicin. Storage at 5 degrees C tended to maintain better semen quality
      irrespective of oxygen exposure, and did not necessitate an antibiotic treatment.

PMID- 18042209
TI  - Functional activity of frozen thawed Chinchilla lanigera spermatozoa
      cryopreserved with glycerol or ethylene glycol.
AB  - The cryopreservation of spermatozoa constitutes a valuable tool for the captive
      breeding management of valuable and/or threatened species. Chinchilla lanigera is
      a species almost extinct in the wild, and the domestic counterpart has one of the
      most valuable pelts in the world. The objectives of this study were to: (i)
      compare the functional activity of post-thawed chinchilla spermatozoa
      cryopreserved at -196 degrees C either with glycerol (G) or ethylene glycol (EG)
      as cryoprotectants (1 m final concentration) and (ii) investigate the effects of
      incubating the gametes for 4 h in the presence or in the absence of the
      cryoprotectants; evaluations were performed taking into account motility,
      viability, response to hypo-osmotic shock and acrosome integrity of the cells.
      Parameters reflecting post-thaw (0 h) sperm functional activity were
      significantly lower than those of freshly ejaculated gametes. When comparing the
      cryoprotectant efficiency of G vs EG, neither cryoprotectant agent offered
      appreciable advantages. After 4 h of incubation, in the presence or absence of
      the cryoprotectant agent, a rapid and significant decrease was found in all
      functional parameters and remained at approximately 20-30% motile, viable and
      viable acrosome intact cells. Viability was significantly lower when the
      cryoprotectant was removed from the media (possibly due to the centrifugation
      process). With respect to the maintenance of sperm membrane integrity, only
      approximately 10% of cells showed membrane resistance to hypo-osmotic conditions
      after the 4 h incubation period. These results constitute new insights for
      cryopreservation protocols and the development of assisted reproductive
      techniques in this species.

PMID- 18042210
TI  - Effects of feeding level during lactation on FSH and LH secretion patterns, and
      follicular development in primiparous sows.
AB  - In the primiparous lactating sow undernutrition affects LH, but the effect on FSH
      is less clear. This study was conducted to investigate the effect of ad libitum
      (AL; n = 5) and restricted (RE; 70% of the AL feed; n = 5) feeding on the
      secretion patterns of FSH and LH, and on follicular development in primiparous
      lactating sows. Body side fat thickness (BSFT) was measured prior to farrowing
      and at weaning on day 21 postpartum (pp). Sows had an intravenous catheter fitted
      on day 6 or 7 pp. Blood samples were taken on days 12, 15 and 18 pp, every 15 min
      starting at 0700 h for 11 h, and plasma analysed for FSH and LH by
      radioimmunoassay (RIA). Daily transcutaneous ultrasonography of the ovaries was
      performed between days 10 and 20 pp to monitor follicular growth. Reduction in
      BSFT was higher in RE than in AL sows (p < 0.05). Mean and basal LH were
      significantly higher in AL than in RE sows on days 12 and 15 pp. (p < 0.05), and
      LH pulse frequency tended to be higher (p < 0.1). Mean FSH was higher in AL than
      in RE sows on days 15 and 18 (p < 0.05), and had a tendency to be higher on day
      12 (p = 0.1). Follicle size increased in AL sows between days 10 and 20 of
      lactation (p < 0.05; r = 0.71), but remained unaffected in RE sows. In
      conclusion, the study demonstrates that feed restriction of primiparous sows
      during lactation affects not only LH, but also FSH, as well as lactational
      follicular growth. An association between those events is suggested.

PMID- 18042211
TI  - Nurses' critical event risk assessments: a judgement analysis.
AB  - AIMS: To explore and explain nurses' use of readily available clinical
      information when deciding whether a patient is at risk of a critical event.
      BACKGROUND: Half of inpatients who suffer a cardiac arrest have documented but
      unacted upon clinical signs of deterioration in the 24 hours prior to the event.
      Nurses appear to be both misinterpreting and mismanaging the nursing-knowledge
      'basics' such as heart rate, respiratory rate and oxygenation. Whilst many
      medical interventions originate from nurses, up to 26% of nurses' responses to
      abnormal signs result in delays of between one and three hours. METHODS: A double
      system judgement analysis using Brunswik's lens model of cognition was undertaken
      with 245 Dutch, UK, Canadian and Australian acute care nurses. Nurses were asked
      to judge the likelihood of a critical event, 'at-risk' status, and whether they
      would intervene in response to 50 computer-presented clinical scenarios in which
      data on heart rate, systolic blood pressure, urine output, oxygen saturation,
      conscious level and oxygenation support were varied. Nurses were also presented
      with a protocol recommendation and also placed under time pressure for some of
      the scenarios. The ecological criterion was the predicted level of risk from the
      Modified Early Warning Score assessments of 232 UK acute care inpatients.
      RESULTS: Despite receiving identical information, nurses varied considerably in
      their risk assessments. The differences can be partly explained by variability in
      weightings given to information. Time and protocol recommendations were given
      more weighting than clinical information for key dichotomous choices such as
      classifying a patient as 'at risk' and deciding to intervene. Nurses' weighting
      of cues did not mirror the same information's contribution to risk in real
      patients. Nurses synthesized information in non-linear ways that contributed
      little to decisional accuracy. The low-moderate achievement (R(a)) statistics
      suggests that nurses' assessments of risk were largely inaccurate; these
      assessments were applied consistently among 'patients' (scenarios). Critical care
      experience was statistically associated with estimates of risk, but not with the
      decision to intervene. CONCLUSION: Nurses overestimated the risk and the need to
      intervene in simulated paper patients at risk of a critical event. This average
      response masked considerable variation in risk predictions, the need for action
      and the weighting afforded to the information they had available to them. Nurses
      did not make use of the linear reasoning required for accurate risk predictions
      in this task. They also failed to employ any unique knowledge that could be shown
      to make them more accurate. The influence of time pressure and protocol
      recommendations depended on the kind of judgement faced suggesting then that
      knowing more about the types of decisions nurses face may influence information
      use. RELEVANCE TO CLINICAL PRACTICE: Practice developers and educators need to
      pay attention to the quality of nurses' clinical experience as well as the
      quantity when developing judgement expertise in nurses. Intuitive unaided
      decision making in the assessment of risk may not be as accurate as supported
      decision making. Practice developers and educators should consider teaching
      nurses normative rules for revising probabilities (even subjective ones) such as
      Bayes' rule for diagnostic or assessment judgements and also that linear ways of
      thinking, in which decision support may help, may be useful for many choices that
      nurses face. Nursing needs to separate the rhetoric of 'holism' and 'expertise'
      from the science of predictive validity, accuracy and competence in judgement and
      decision making.

PMID- 18042212
TI  - Isolation of hexachlorocyclohexane-degrading Sphingomonas sp. by dehalogenase
      assay and characterization of genes involved in gamma-HCH degradation.
AB  - AIM: To screen and identify bacteria from contaminated soil samples which can
      degrade hexachlorocyclohexane (HCH)-isomers based on dechlorinase enzyme activity
      and characterize genes and metabolites. METHODS AND RESULTS: Dechlorinase
      activity assays were used to screen bacteria from contaminated soil samples for
      HCH-degrading activity. A bacterium able to grow on alpha-, beta-, gamma- and
      delta-HCH as the sole carbon and energy source was identified. This bacterium was
      a novel species belonging to the Sphingomonas and harbour linABCDE genes similar
      to those found in other HCH degraders. Gamma-pentachlorocyclohexene 1,2,4
      trichlorobenzene and chlorohydroquinone were identified as metabolites.
      CONCLUSIONS: The study demonstrates that HCH-degrading bacteria can be identified
      from large environmental sample-based dehalogenase enzyme assay. This kind of
      screening is more advantageous compared to selective enrichment as it is specific
      and rapid and can be performed in a high-throughput manner to screen bacteria for
      chlorinated compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: The chlorinated
      pesticide HCH is a persistent and toxic environmental pollutant which needs to be
      remediated. Isolation of diverse bacterial species capable of degrading all the
      isomers of HCH will help in large-scale bioremediation in various parts of the
      world.

PMID- 18042213
TI  - Used cot mattresses as potential reservoirs of bacterial infection: nutrient
      availability within polyurethane foam.
AB  - AIM: To evaluate possible source of nutrients for bacterial growth within
      polyurethane (PU) foam of used cot mattresses as determinants of bacterial
      population density. METHODS AND RESULTS: Used infant mattresses (n = 30) were
      analysed for bacteria capable of degrading colloidal PU and for aqueous soluble
      chemical components (aromatic amines, ammonium ions, phosphates and protein).
      Mattress type (waterproof cover vs exposed PU foam at the infant-head region),
      mattress age and previous use by another child were evaluated as factors that
      could influence the measured parameters. The levels of protein extracted from PU
      foam were (i) significantly (P = 0.0019) higher for mattresses lacking a
      waterproof cover at the infant-head region and (ii) positively correlated with
      both culturable bacterial population densities of the PU foams and extent of
      growth of Staphylococcus aureus on aqueous leachates. No statistically
      significant (P > 0.05) associations between other measured parameters and
      mattress type/use factors were identified. CONCLUSIONS: Infant use of cot
      mattresses with exposed PU foam leads to accumulation of proteins within the PU,
      which can promote bacterial growth. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      study provides a mechanistic explanation for increased levels of bacteria
      associated with exposed PU of cot mattresses. In the context of the common
      bacterial toxins hypothesis for the sudden infant death syndrome (SIDS), this
      could explain the lowered risk of SIDS associated with use of a waterproof cover
      above the mattress.

PMID- 18042214
TI  - Urologist practice patterns in the management of Peyronie's disease: a nationwide
      survey.
AB  - INTRODUCTION: Peyronie's disease (PD) is a poorly understood clinical entity.
      Aim. We endeavored to determine how contemporary urologists in the United States
      manage PD. METHODS: A randomly generated mailing list of 996 practicing
      urologists was generated from the American Urologic Association member directory.
      A specifically designed survey was mailed with a cover letter and a postage-paid
      return envelope. MAIN OUTCOME MEASURE: Our survey assessed several practice
      related factors and asked questions of how the subject would manage various
      presentations of PD in their practice. Four cases were presented: case 1, a
      healthy 55-year-old man with painless 30 degrees dorsal curvature of 16 months
      duration; case 2, a 60-year-old man with 35 degrees dorsal curvature, 4/10 pain
      on visual analog scale, of 6 months duration; case 3, a 62-year-old man with
      painless 60 degrees dorsal curvature and erectile dysfunction responsive to
      alprostadil suppository of 2 years duration; and case 4, a 50-year-old man with
      mid-shaft waist deformity, foreshortening, no pain/curvature/erectile
      dysfunction. RESULTS: Responses were received from 236 (24%) practicing
      urologists. Vitamin E was the preferred initial management for 70% of
      respondents, with observation, Potaba (Glenwood, Englewood, New Jersey, USA),
      colchicine, verapamil injections, and verapamil gel favored by 32, 20, 12, 7, and
      10% of respondents, respectively. Fifty-seven percent of respondents performed
      surgery for PD, with penile prostheses, Nesbit procedure, grafting, and plication
      used by 76, 66, 55, and 51% of respondents, respectively. Medical therapy and/or
      observation was the preferred management for all of the cases except case 3, for
      which penile prosthesis placement and referral were the favored options by 39 and
      30% of urologists, respectively. CONCLUSIONS: Medical therapy is the initial
      treatment for PD among American urologists. Penile prosthesis is the treatment of
      choice in impotent patients. Most American urologists conform to recommended
      practice patterns in the management of PD.

PMID- 18042215
TI  - Validation of the female sexual distress scale-revised for assessing distress in
      women with hypoactive sexual desire disorder.
AB  - INTRODUCTION: The concept of sexually related personal distress is currently
      central to the diagnosis of all female sexual dysfunctions (FSD). In the current
      study, we have focused on validating a slightly revised version of the Female
      Sexual Distress Scale (FSDS), the FSDS-Revised (FSDS-R), to enhance the
      sensitivity of the instrument with patients suffering from hypoactive sexual
      desire disorder (HSDD). In addition, we have attempted to extend the validation
      generalizability of the scale by demonstrating that both instruments possess
      reliability and discriminative validity in premenopausal women with HSDD. AIM: To
      assess the validity of the revised version of the FSDS, the FSDS-R, for measuring
      sexual distress in women with HSDD. METHODS: A prospective methodological study
      carried out at 27 centers in North America enrolled 296 women aged 18-50 years
      with HSDD, another female sexual dysfunction (FSD), or no FSD. The subjects
      completed the FSDS-R at baseline, day 7, and day 28, with a 30-day recall at
      baseline and with a 7-day recall on days 7 and 28. MAIN OUTCOME MEASURES:
      Receiver operating characteristic (ROC) analyses of FSDS, FSDS-R, and FSDS-R item
      13 were used for the differentiation of HSDD from no FSD, while intraclass
      correlation coefficient (ICC) was used to estimate test-retest reliability.
      Cronbach's coefficient alpha was used to measure the internal consistency of the
      FSDS-R and Pearson's correlation coefficient to assess FSDS, FSDS-R, and FSDS-R
      item 13 with different recall periods (7 and 30 days). RESULTS: Mean total FSDS,
      FSDS-R, and FSDS-R item 13 scores with either recall period were significantly
      higher (P < 0.0001) in women with FSD or HSDD than in women with no FSD, showing
      both tests had discriminant validity. ROC analysis confirmed these findings,
      while an ICC of >0.74 showed the test-retest reliability of both scales,
      including FSDS-R item 13 alone, and Cronbach's coefficient alpha of >0.86
      confirmed the internal consistency of both tests. CONCLUSIONS: Consistent with
      the FSDS, the FSDS-R demonstrated good discriminant validity, high test-retest
      reliability, and a high degree of internal consistency in measuring sexually
      related personal distress in women with HSDD. FSDS-R item 13 alone also
      demonstrated good discriminant validity and test-retest reliability.

PMID- 18042216
TI  - Female sexual function after surgery for stress urinary incontinence:
      transobturator suburethral tape vs. tension-free vaginal tape obturator.
AB  - INTRODUCTION: The transobturator suburethral tape (TOT) and tension-free vaginal
      tape obturator (TVT-O) procedures are relatively new incontinence treatment
      procedures. Studies on the influence on sexual function as a result of these
      procedures are limited. AIM: The influence of TOT or TVT-O for the surgical
      treatment of stress urinary incontinence (SUI) on female sexual function.
      METHODS: We evaluated 77 sexually active patients after TVT-O (N = 34, mean age
      53.2 years) and TOT (OB-TAPE, Porges) (N = 44, mean age 52.0 years) placement for
      SUI based on the responses to a mailed questionnaire 3 months after the
      operation. MAIN OUTCOME MEASURE: Difference in postoperative sexual complaints
      related to the TVT-O (inside-out) and TOT (outside-in) procedure. RESULTS:
      Postoperative TOT and TVT-O: There was almost no difference in frequency of
      sexual intercourse and an improvement of the continence during intercourse;
      continence was reported in 33 patients (42.3%) before and 67 patients (78.4%)
      after operation. The appreciation of sexual intercourse was improved in 15
      patients (19.2%) and worsened in eight patients (10.3%). Postoperative TVT-O vs.
      TOT: No difference was seen in lost of lubrication, clitoral tumescence
      reduction, and clitoral sensibility reduction between both procedures. Pain
      because of vaginal narrowing was seen significantly more in the TOT procedure
      group. CONCLUSION: Overall, in this study, the technique of TOT gave rise to more
      sexual dysfunction than TVT-O. However, because of the successful outcome on
      incontinence, both procedures had, overall, a positive effect on sexual function.
      The cause of significant more pain during intercourse as a result of vaginal
      narrowing in the TOT procedure requires further investigation. Like other
      studies, this study demonstrated that incontinence surgery can have a positive
      and negative outcome on sexual function. It is important to put this issue in the
      informed consent.

PMID- 18042217
TI  - How urologists manage erectile dysfunction after radical prostatectomy: a
      national survey (REPAIR) by the French urological association.
AB  - INTRODUCTION: There is little sound information on how urologists manage erectile
      dysfunction (ED) arising after radical prostatectomy (RP) in a real-world
      situation. AIM: To perform a national survey of how French urologists manage ED
      after RP in routine practice. MAIN OUTCOME MEASURES: Choice of first-line
      treatment, type of treatment (rehabilitation of erectile function vs. treatment
      on demand for intercourse), and timing and duration of treatment. METHODS: All
      French urologists were invited to take part in a survey; 59.7% accepted
      provisionally (760/1,272). They received the survey questionnaire and 10 patient
      data forms to be completed during the visits of the first 10 patients with fewer
      than 12 months follow-up post-RP. These were returned to an independent third
      party for analysis. RESULTS: The final response rate was 535/1,272 (42%). Before
      performing RP, 80% of the urologists assessed sexual activity and 76% erectile
      function; 9% did neither. Thirty-eight percent reported that they systematically
      proposed ED treatment to their patients post-RP ("routine prescribers"). The
      remainder was treated on occasion, either at the patients' request (49%) or at
      their own discretion (13%). Routine prescribers tended to be younger and had
      performed more RPs in the preceding year. Most urologists (88%) always used the
      same first-line treatment: regular intracavernosal injections (ICIs) for
      rehabilitation, 39%; ICI on demand for intercourse, 30%; phosphodiesterase type 5
      (PDE5) inhibitors on demand, 16%, or regular PDE5 inhibitors for rehabilitation,
      8%; alternating ICI and PDE5 inhibitors, 7%; vacuum device, <1%. ED treatment was
      initiated within 3 months of RP by 72% of the urologists (92% of routine
      prescribers). The percentage of urologists recommending ED treatment for 6 months
      was 20%, 38% for 1 year, and 33% for 2 years. CONCLUSION: ED was commonplace
      after RP. French urologists reported a proactive attitude to ED treatment, many
      favoring pharmacologic rehabilitation therapy. ICI was their first-line treatment
      of choice.

PMID- 18042218
TI  - Vaginal vasomotion--its appearance, measurement, and usefulness in assessing the
      mechanisms of vasodilatation.
AB  - INTRODUCTION: In a number of tissue microcirculations, the phenomenon of
      vasomotion occurs where only a proportion of the total number of capillaries
      present are open at the same time; they normally open and close in a random or
      chaotic order, partly determined by the metabolic state of their surrounding
      cells. AIM: A pilot to examine by photoplethysmography whether the vaginal
      microcirculation shows evidence of vasomotion and the effect when sexual arousal
      is induced. METHODS: The vaginal microcirculation in 14 healthy, premenopausal
      women was monitored by intravaginal infrared photoplethysmography using the
      vaginal pulse amplitude (VPA) as the index of blood content in the basal
      condition and during sexual arousal induced by video and/or clitoral stimulation.
      MAIN OUTCOME MEASURE: Analysis and interpretation of vaginal
      photoplethysmographic traces. RESULTS: The basal traces in all the sexually
      unaroused subjects (N = 14) showed at least two populations of their VPAs: a high
      amplitude VPA (h-VPA) with rapid ascending phase (short duration of systolic
      infill) and descending phase (short duration of diastolic outflow) among which
      were pseudorandomly scattered, low amplitude VPAs (l-VPA) with less acute
      ascending and descending phases; the l-VPAs were usually half the amplitude of
      the h-VPAs. On sexual arousal, the l-VPAs were converted into h-VPAs so that the
      l-VPAs decreased and in some cases practically disappeared, and the h-VPAs
      usually showed an increase; with cessation of the vasodilatory stimulus (N = 6),
      there was a slow recovery of the l-VPAs. The induction of orgasm did not appear
      to facilitate their recovery. Even during a short duration of sexual arousal (1
      minute), the decrease in the l-VPAs (N = 6) was a more sensitive index of the
      occurrence of genital arousal than relying solely on changes in the maximum
      amplitude of the VPA. CONCLUSION: Because of vasomotion, the vaginal
      microcirculation can react to a vasodilatory stimulus with one of four
      theoretical photoplethysmographic responses, viz., Type 1 (full response), where
      there is a significant increase in the amplitude of the h-VPA signal and the
      number of l-VPAs are greatly reduced with a near corresponding increase in the h
      VPAs; Type 2 (partial response), where the amplitude (and in some cases the
      number) of the h-VPAs increases but there is no decrease in the number of l-VPAs;
      Type 3 (partial response), where the amplitude of the h-VPAs changes little but
      the number of l-VPAs is reduced and the number of h-VPAs are correspondingly
      increased; and Type 4, where neither the amplitude of the h-VPAs (or their
      number) nor the number of the l-VPAs change significantly (a noneffective
      stimulus). This new analysis allows a more comprehensive and better
      discriminatory assessment of vaginal vasodilatation (genital arousal) and its
      return to the basal state in response to sexual arousal and now includes a new
      measure that is independent of an increase in the h-VPA maximum amplitude (Type 3
      response).

PMID- 18042219
TI  - Evaluation of the psychometric properties of the life satisfaction checklist as a
      screening tool for erectile dysfunction.
AB  - INTRODUCTION: There is a need for a more feasible and acceptable screening tool
      for erectile dysfunction (ED) in our health context. The Fugl-Meyer's Life
      Satisfaction Checklist (LISAT-8) has been shown to be a simple and good
      instrument for assessing the satisfaction of ED patients in different aspects of
      their lives and has also shown acceptable psychometric properties to be used in
      the Spanish population with ED. Furthermore, this checklist has been used as a
      screening tool in patients with and without ED, showing valid and reliable
      properties for detection of ED. AIM: To evaluate the validity and feasibility of
      LISAT-8 checklist as a screening tool to detect ED. METHODS AND MAIN OUTCOME
      MEASURES: A cross-sectional, multicenter, and observational study was conducted
      including 6,986 Spanish men aged over 18 years. Patients completed the
      International Index of Erectile Function (IIEF), Sexual Health Inventory for Men
      (SHIM) and LISAT-8 checklists. Questions about the simplicity of SHIM and LISAT-8
      and time to complete them were used for feasibility evaluation. We used logistic
      regression analysis to select the best predictors for ED among the different
      items of LISAT-8 and the receiver operating characteristic (ROC) curve analysis
      to select the best cutoff value discriminating ED vs. non-ED subjects.
      Sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV), along with kappa agreement coefficient, were also
      estimated. RESULTS: A total of 6,986 patients were included. Among the patients,
      71.2% preferred LISAT-8 to SHIM. Time to completion of checklist was 0.5 minute
      less with LISAT-8 than with SHIM (P < 00001). Items 2 (sexual life), 5 (contacts
      with friends and acquaintances), and 3 (partner relationship) of LISAT-8 were
      selected as predictors for ED. ROC curve analysis showed a cutoff point >/=15
      with a sensitivity of 81.7% (95% confidence intervals: 80.5-82.9), a specificity
      of 79.2% (77.5-80.8), and PPV of 88.7% (87.6-89.8%) and NPV of 72.0% (70.0
      73.0%). Kappa agreement coefficients were 0.57 (LISAT-8 vs. SHIM) and 0.60 (LISAT
      8 vs. IIEF). CONCLUSIONS: LISAT-8 and its composite variable (formed by items 2 +
      3 + 5) showed acceptable psychometric properties, and it could be a valid
      screening tool for ED in daily clinical practice.

PMID- 18042220
TI  - Haemoglobin-vesicles as artificial oxygen carriers: present situation and future
      visions.
AB  - During the long history of development of haemoglobin (Hb)-based O2 carriers
      (HBOCs), many side effects of Hb molecules have become apparent. They imply the
      physiological importance of the cellular structure of red blood cells. Hb
      vesicles (HbV) are artificial O2 carriers that encapsulate concentrated Hb
      solution with a thin lipid membrane. We have overcome the intrinsic issues of the
      suspension of HbV as a molecular assembly, such as stability for storage and in
      blood circulation, blood compatibility and prompt degradation in the
      reticuloendothelial system. Animal tests clarified the efficacy of HbV as a
      transfusion alternative and the possibility for other clinical applications. The
      results of ongoing HbV research make us confident in advancing further
      development of HbV, with the expectation of its eventual realization.

PMID- 18042221
TI  - Peroxisome proliferator-activated receptors--from active regulators of macrophage
      biology to pharmacological targets in the treatment of cardiovascular disease.
AB  - Altered macrophage functions contribute to the pathogenesis of many infectious,
      immunological and inflammatory disease processes. Pharmacological modulation of
      macrophage activities therefore represents an important strategy for the
      prevention and treatment of inflammation-related diseases, such as
      atherosclerosis. This review focuses on recent advances on the role of the
      peroxisome proliferator-activated receptor transcription factor family in the
      modulation of lipid homeostasis and the inflammatory response in macrophages and
      the potential participation of these actions in the modulation of metabolic and
      cardiovascular disease.

PMID- 18042222
TI  - Clinical long-term evaluation of MTA as a direct pulp capping material in primary
      teeth.
AB  - AIM: To evaluate the effectiveness of mineral trioxide aggregate (MTA) when used
      as a pulp capping material in primary teeth. METHODOLOGY: Clinical follow-up was
      performed on 25 symmetrical pairs of primary molars with deep occlusal caries, in
      25 patients between the ages of 5 and 8 years. Pulps exposed during cavity
      preparation were treated by direct pulp capping with MTA or calcium hydroxide,
      based with resin-bonded zinc oxide eugenol cement and restored with amalgam.
      Clinical and radiographic examinations were carried out at 1, 3, 6, 9, 12, 18 and
      24 months. RESULTS: Twenty-four-month clinical and radiographic follow-ups were
      carried out on 22 patients. One patient failed to return for evaluation after 1
      month, one after 9 months and another after 12 months. During follow-up, none of
      the MTA and calcium hydroxide groups exhibited clinical or radiographic failure.
      CONCLUSIONS: Mineral trioxide aggregate was found to be as successful as calcium
      hydroxide when used for direct pulp capping in primary teeth. Further
      histological investigations are needed to support these findings.

PMID- 18042223
TI  - Mineral trioxide aggregate in the treatment of external invasive resorption: a
      case report.
AB  - AIM: To describe the management of external invasive resorption using mineral
      trioxide aggregate (MTA). SUMMARY: External invasive root resorption may occur as
      a consequence of trauma, orthodontic treatment, intracoronal bleaching and
      surgical procedures, and may lead to the progressive and destructive loss of
      tooth structure. Depending on the extent of the resorptive process, different
      treatment regimens have been proposed. A 19-year-old male patient presented with
      tooth 11 (FDI) showing signs and symptoms of irreversible pulpitis, external
      invasive resorption and periodontal pocket on the disto-palatal. After root canal
      treatment, the defect was accessed coronally. The resorption area was chemo
      mechanically debrided using ultrasonic tips and irrigant solution. MTA was used
      to fill the resorptive defect, and the coronal access was temporarily sealed. The
      definitive coronal restoration was performed after 3 days. Radiographs at 1, 2
      and 4 years showed adequate repair of the resorption and endodontic success.
      Clinically, the tooth was asymptomatic, and no periodontal pocket was found. KEY
      LEARNING POINTS: *Mineral trioxide aggregate was successfully used to restore a
      small area of external invasive resorption. *A coronal approach can sometimes be
      successfully used in order to avoid surgery and periodontal complications.

PMID- 18042224
TI  - Replantation of a vertically fractured maxillary central incisor after repair
      with adhesive resin.
AB  - AIM: To describe the replantation of a vertically fractured root-filled maxillary
      central incisor after repair with adhesive resin. SUMMARY: Root-filled teeth with
      vertical root fractures are usually extracted as they generally have a poor
      prognosis. In this case, an 18-month follow-up of a replanted incisor with
      vertical root fracture is presented with clinical and radiographic documentation.
      KEY LEARNING POINTS: * Replantation of root-filled incisors with complete
      vertical root fracture after resin bonding might be a realistic alternative to
      extraction. * Practitioners should be aware of the possible disadvantages as well
      as advantages associated with failure of a replanted incisor with complete
      vertical root fracture.

PMID- 18042225
TI  - Heat stress induces alkaline phosphatase activity and heat shock protein 25
      expression in cultured pulp cells.
AB  - AIM: To investigate the responses of cultured rat pulp cells to heat stress.
      METHODOLOGY: Pulp cells were obtained from rat incisors and cultured at 37
      degrees C. The cells were cultured at 42 degrees C for 30 min and then cultured
      at 37 degrees C again. Morphology, alkaline phosphatase (ALP) activity and
      expression of heat shock protein 25 (HSP25) were investigated at 0, 1, 3, 5, 7,
      10 and 14 days following stimulation. As a control, the cells were maintained at
      37 degrees C. RESULTS: Although there were few cells of apoptosis immediately
      after heat stress, there were mitotic cells from day 1 after heat stress. ALP
      activity in the heat stress group significantly increased at days 7 and 14
      compared with the control group (about 1.7-fold, P < 0.01, Friedman test). HSP25
      expression increased in both groups, with HSP25 in the heat stress group being
      expressed earlier than in the control group, and nuclear localization of HSP25
      was observed at days 0 and 1 in heat-stressed cells. CONCLUSION: These results
      suggest that heat stress not only induces HSP25 but also enhances ALP activity in
      pulp cells.

PMID- 18042226
TI  - The effect of pH on surface hardness and microstructure of mineral trioxide
      aggregate.
AB  - AIM: To evaluate the surface microhardness of mineral trioxide aggregate (MTA)
      specimens following exposure of their surface to a range of acidic environments
      during hydration. In addition, the morphological microstructure features of
      samples were studied by scanning electron microscopy (SEM). METHODOLOGY: White
      ProRoot MTA (Dentsply Tulsa Dental, Johnson City, TN, USA) was mixed and packed
      into cylindrical polycarbonate tubes. Four groups, each of 10 specimens, were
      formed using a pressure of 3.22 MPa and exposed to pH 4.4, 5.4, 6.4 and 7.4,
      respectively, for 4 days. Vickers microhardness of the surface of each specimen
      was measured after exposure. Four groups of two specimens were prepared and
      treated in the same way prior to qualitative examination by SEM. Data were
      subjected to one-way anova and post hoc Tukey's test. RESULT: The greatest mean
      surface hardness values (53.19 +/- 4.124) were observed following exposure to pH
      7.4 with the values decreasing to 14.34 +/- 6.477 following exposure to pH 4.4.
      The difference between these values at the 95% CI (33.39-44.30) was statistically
      significant (P < 0.0001). There were no distinct morphological differences
      between groups in terms of the internal microstructure. However, a trend was
      observed that the more acidic the solution, the more extensive the porosity of
      the specimens. CONCLUSION: Under the conditions of this study, surface hardness
      of MTA was impaired in an acidic environment.

PMID- 18042227
TI  - Biopsychosocial correlates of headache: what predicts pediatric headache
      occurrence?
AB  - OBJECTIVE: The study aims at identifying biopsychosocial risk factors for
      headache in children and adolescents aged 9 to 14. METHODS: An epidemiological
      survey was conducted in a randomly drawn population sample of families with
      children in the above age group. Questionnaires were mailed to parents and
      children (n=6400), on whose data this report is based. The objective of the study
      was to establish a profile of risk factors regarding the occurrence of headache.
      Headache, as the criterion variable, was ranked according to its frequency in the
      last 6 months (no, rare, monthly, weekly). Independent variables came from 6
      domains: health, socioeconomic, family, school, leisure/peers, and psychological
      factors. Data analysis was conducted via multinomial regression analyses in a 4
      step strategy: (1) analysis of age and sex as control variables; (2) analysis of
      single variables from each of the 6 domains (controlled for age and sex); (3)
      domain analyses; and (4) comprehensive analysis including all significant
      variables from the domain analyses. RESULTS: Age and sex explained a small but
      significant proportion of the variance in headache frequency (3.5%). All health
      variables, several socioeconomic, and most family- and school-related as well as
      the psychological variables demonstrated a significant association with the
      criterion in the single variable models. However, only a few of the variables
      related to leisure/peer activities reached significance. The domain model
      comprising health variables explained 27% of the variance, achieving the best
      model fit, followed by the psychological model with 13%. CONCLUSIONS: The
      comprehensive model was able to explain one third of the total variance in
      headache occurrence. Contrary to our hypothesis, the addition of psychosocial
      variables to health-related predictors did not markedly improve model fit.

PMID- 18042228
TI  - Patterns of hepatocellular carcinoma incidence in Egypt from a population-based
      cancer registry.
AB  - AIM: Hepatocellular carcinoma (HCC) is increasing worldwide, and is frequently
      attributed to rising rates of hepatitis C virus infection and interactions
      between viral and environmental risk factors. Because of Egypt's unique risk
      factor profile, we analyzed data from the Gharbiah Population-Based Cancer
      Registry for the period 1999-2003 to characterize demographic and geographic
      patterns of cases in this province. METHODS: We calculated age- and sex-specific
      and age- and sex-standardized HCC incidence rates for the eight districts in
      Gharbiah. We also compared rates from Gharbiah with the USA (US Surveillance
      Epidemiology and End RESULTS [SEER] database). RESULTS: The analysis revealed a
      higher incidence in males than in females, significant geographic variations
      among districts, and a higher incidence in Gharbiah than that reported by SEER.
      CONCLUSION: The findings of this study document the heterogeneous distribution of
      HCC at regional and international levels. This population-based registry offers
      the opportunity for careful representative studies of various etiologies,
      particularly infectious and/or environmental factors that may contribute to risk.

PMID- 18042229
TI  - Botulinum Toxin Type A in the treatment of chronic migraine without medication
      overuse.
AB  - INTRODUCTION: Chronic migraine is a recent diagnostic term that has undergone
      evolution from its original description. Clinically it has been believed that
      medication overuse contributed to its development and would block attempts at
      prevention. Previous studies with Botulinum Toxin Type A have demonstrated that
      it is effective even in patients with medication overuse. This study undertakes
      to examine the effects of Botulinum Toxin Type A in the absence of medication
      overuse in patients with chronic migraine. STUDY DESIGN: Double-blind placebo
      controlled randomized trial of Botulinum Toxin Type A 100 units administered in a
      fixed dose and site paradigm. PATIENTS: In total, 86 patients were enrolled. A
      total of 60 patients were randomized and 41 patients were treated with the study
      medication or placebo. Five patients failed to complete the study, which lasted 4
      months after the study medication was injected. RESULTS: Botulinum Toxin Type A
      was statistically superior to placebo for the primary endpoint of reduction in
      migraine headache episodes. Six patients on Botulinum Toxin Type A compared with
      3 patients on Placebo had at least a 50% reduction in their migraine episodes.
      Active treatment was superior to placebo for the secondary endpoints of total
      headache days, headache index, and quality of life measures. It showed numerical
      superiority to placebo for acute medication use and Migraine Disability
      Assessment Scores. Adverse events were rare and similar in both treatment groups.
      CONCLUSIONS: The use of Botulinum Toxin Type A may be an effective treatment for
      chronic migraine when the patient does not have concomitant medication overuse.
      It was well tolerated in this trial.

PMID- 18042230
TI  - Quantification of class 1 integron abundance in natural environments using real
      time quantitative PCR.
AB  - Integrons are bacterial genetic elements capable of capturing and expressing
      potentially adaptive genetic material. Class 1 integrons constitute the most
      intensely studied group of these elements to date, mainly due to their well
      established role in the acquisition and dissemination of antibiotic resistance
      genes in clinical environments. However, virtually nothing is known about the
      distribution or abundance of class 1 integrons outside of the clinical context.
      Here we develop a SYBR Green-based real-time quantitative PCR assay capable of
      quantifying the abundance of class 1 integrons in environmental samples. It was
      shown that the abundance of the intI1 gene in creek sediment correlates with
      ecological condition, implying that class 1 integrons provide selective
      advantages relevant to environmental pressures other than the use of antibiotics.
      By comparing the quantities of intI1 and 16S rRNA gene in each sample, it was
      demonstrated that approximately 2.7% of cells potentially harbour a class 1
      integron. These findings suggest that class 1 integrons are widespread in natural
      environments removed from clinical settings and occur in a broader range of host
      organisms than had previously been assumed on the basis of culture-dependent
      estimates.

PMID- 18042231
TI  - Characterization of glucose transport mutants of Saccharomyces cerevisiae during
      a nutritional upshift reveals a correlation between metabolite levels and
      glycolytic flux.
AB  - Saccharomyces cerevisiae shows a marked preference for glucose and fructose,
      revealed by the repression of genes whose products are involved in processing
      other carbon sources. This response seems to be driven by sugar phosphorylation
      in the first steps of glycolysis rather than by the external sugar concentration.
      To gain a further insight into the role of the internal sugar signalling
      mechanisms, were measured the levels of upper intracellular glycolytic
      metabolites and adenine nucleotides in three mutant strains, HXT1, HXT7 and TM6*,
      with progressively reduced uptake capacities in comparison with the wild type.
      Reducing the rate of sugar consumption caused an accumulation of hexose
      phosphates upstream of the phosphofructokinase (PFK) and a reduction of fructose
      1,6-bisphosphate levels. Mathematical modelling showed that these effects may be
      explained by changes in the kinetics of PFK and phosphoglucose isomerase.
      Moreover, the model indicated a modified sensitivity of the pyruvate
      dehydrogenase and the trichloroacetic acid cycle enzymes towards the NAD/NADH in
      the TM6* strain. The activation of the SNF1 sugar signalling pathway, previously
      observed in the TM6* strain, does not correlate with a reduction of the ATP : AMP
      ratio as reported in mammals. The mechanisms that may control the glycolytic rate
      at reduced sugar transport rates are discussed.

PMID- 18042232
TI  - Defining the spectrum of international practice in pediatric epilepsy surgery
      patients.
AB  - PURPOSE: The Pediatric Epilepsy Surgery Sub-commission of the International
      League Against Epilepsy conducted a survey to determine the frequency of epilepsy
      procedures and etiologies. METHODS: Data were gathered from 20 programs in the
      United States, Europe, and Australia on 543 patients (<18 years) for calendar
      year 2004. RESULTS: Age at seizure onset was 1 year or less in 46% of patients.
      Intracranial electrodes were used in 27% of patients. The most common final
      operation was lobar and focal resections of the frontal and temporal lobes (41%),
      followed by cerebral hemispherectomy (16%), vagus nerve stimulator (16%), and
      multilobar resections (13%). Multiple-subpial transections were uncommon
      procedures (0.6%). The most frequent etiologies were cortical dysplasia (42%),
      tumors (19%), and atrophic lesions and strokes (10%). Less common were vascular
      lesions (1.5%), Rasmussen encephalitis (3%), Sturge-Weber (3%), and operations
      for infantile spasms (4%), and Landau-Kleffner/ESES (<2%). Children <4 years
      generally presented with daily seizures from cortical dysplasia and underwent
      multilobar or hemispherectomy. Previous surgeries before 2004 were reported in
      22%, and occurred more commonly in patients with tumors (40%), hypothalamic
      hamartomas (47%), and vascular lesions (67%). U.S. centers reported more vagus
      nerve stimulator procedures, operated more often on children with no or subtle
      MRI findings, and used intracranial electrodes and functional neuroimaging more
      frequently than programs in Europe and Australia. CONCLUSIONS: The results of
      this international survey show the feasibility of international collaborations in
      determining epilepsy etiologies and procedures in children, and suggest
      differences in clinical practice between regions of the world. These results can
      guide the design of future studies in producing guidelines for therapy-resistant
      pediatric epilepsy surgery patients.

PMID- 18042233
TI  - Epstein-Barr virus reactivation and multiple sclerosis.
AB  - Infection with Epstein-Barr virus (EBV) is considered one of the possible key
      environmental factors in the aetiology of multiple sclerosis (MS). Whether EBV
      plays an underlying role as an activator of MS remains, however, controversial.
      Sixty-one patients with definite relapsing-remitting multiple sclerosis (RRMS)
      according to the Poser criteria were followed for 1 year. Blood samples were
      drawn at baseline, months 3, 6 and 12, and in case of any clinical exacerbation.
      Twenty-three baseline-paired exacerbation samples in the same set were
      quantitatively analysed to examine whether exacerbations in MS were associated
      with a change in anti-diffuse component of the EBV-early antigen (EA-D) IgG
      ratio. All the 61 patients (100%) were anti-viral capsid antigen (VCA) IgG
      positive, one (2%) was anti-VCA IgM positive and 60 (98%) were anti-EBV nuclear
      antigen IgG positive. Mean anti-EA-D IgG at baseline was 0.57 (range 0.12-2.70)
      and at the time of exacerbations 0.61 (range 0.11-2.70). Wilcoxon signed rank
      test revealed no differences between the 23 baseline and paired exacerbation
      samples (P = 0.58). Our findings suggest that reactivation of latent EBV
      infection does not play a significant role for exacerbations in RRMS.

PMID- 18042234
TI  - Brainstem in Machado-Joseph disease: atrophy or small size?
AB  - Machado-Joseph disease (MJD), one of the most common types of hereditary
      spinocerebellar degeneration caused by abnormal expansion of the CAG repeat in
      the MJD1 gene, presents atrophy of the infratentorial structures
      neuropathologically and neuroradiologically. Although a significant positive
      correlation has been reported between infratentorial atrophy and the number of
      expanded CAG repeat units, the exact changing course of brainstem size in the
      individual case remains to be resolved. We investigated seven cases of
      genetically confirmed MJD longitudinally by magnetic resonance imaging with
      observation periods of 4.5-10.6 years. Measurement of the midsagittal areas of
      infratentorial structures disclosed progressive atrophy of the pontine base and
      cerebellum, which correlated significantly with age, whilst midbrain and pontine
      tegmentum showed atrophy with no significant progression, suggesting it was
      better identified as 'small size' and might have mostly been completed before the
      initial symptoms. Such differences between regions in atrophy progression must be
      caused by a difference in the neuropathological course.

PMID- 18042235
TI  - Neuronal nitric oxide synthase C276T polymorphism increases the risk for
      frontotemporal lobar degeneration.
AB  - The neuronal nitric oxide synthase (nNOS) is abundantly expressed in the brain
      and its transcripts have been found in the frontal cerebral cortex. Eighty-nine
      patients with different neurodegenerative tau-related disorders, including 71
      patients with frontotemporal lobar degeneration (FTLD), 12 with progressive
      supranuclear palsy (PSP) and 6 with corticobasal degeneration (CBD), were
      genotyped for the C276T single nucleotide polymorphism (SNP) in exon 29 of the
      nNOS gene and compared with 190 age-matched controls (CON). A significantly
      increased allelic frequency of the T allele was observed in patients compared
      with CON (40.4% vs. 29.7%, P = 0.014, OR: 1.94, CI: 1.15-3.27). Considering each
      disorder separately, significance was reached for FTLD only (39.4%, P = 0.0248
      versus controls, OR: 1.96, CI: 1.11-3.47). However, the frequency of the T allele
      was elevated also in patients with PSP (45.8%) and CBD (41.7%). No differences
      were observed stratifying according to gender or apolipoprotein E status. The
      C276T SNP acts as risk factor for sporadic FTLD, possibly influencing NOS1
      transcription. Studies in larger populations are needed to confirm its role in
      PSP and CBD.

PMID- 18042236
TI  - Prevalence and incidence of multiple sclerosis in Salerno (southern Italy) and
      its province.
AB  - Many multiple sclerosis (MS) prevalence studies in Italian northern and central
      areas, since 1980, have put Italy in a high risk zone; none concerns southern
      Italy. The MS registry of Salerno Center was reviewed, including the city and 16
      towns at different distances (9-149 km) better connected to our Center.
      Population screened: 259 681 persons (Salerno = 136 678; province = 123 003).
      Prevalence day was December 31, 2005. Data on 186 patients were collected of
      which 55 were males, 131 females; crude total prevalence = 71.6263 (62.03-82.303,
      ranging from 50.1128 (Oliveto Citra) to 431.499 (Controne). Salerno prevalence
      rate is 70.9697 (57.41-86.583); standardized = 72.02. Incidence rate ranges from
      2.38585 (1.6-3.39) (1991-95) to 4.31997 (3.24-5.6) (2001-05). Our data can be
      underestimated because some patients could have skipped the local center. This
      emphasizes that the results, except for Sardinia, are comparable to Italian
      literature data. They confirm that this territory is a high risk area for MS.
      There is also an indirect indication against a latitude gradient for MS.

PMID- 18042237
TI  - Paraneoplastic encephalitis associated with ovarian teratoma and N-methyl-D
      aspartate receptor antibodies.

PMID- 18042238
TI  - A potential catastrophic trap: an unusually presenting sellar lesion.
AB  - A 63-year-old man was admitted to our emergency unit complaining headache, vomit
      and vertigo. A MR of the brain showed an expanding lesion within the sellar
      region. A subsequent angio-MR excluded any intracranial vascular malformations.
      Surprisingly, a cerebral angiography performed later on the basis of worsening of
      neurological signs and symptoms, demonstrated an aneurysm of the internal carotid
      artery. At the best of our knowledge, this is the first case of a thrombosis of
      an intracavernous carotid aneurysm mimicking a pituitary apoplexy documented by
      MR and angio-MR. The treatment of a milder syndrome of pituitary apoplexy is
      still controversial. This case would favour conservative treatment opposed to
      surgery at least when an intracavernous extension or invasion of the adenoma
      would limit the opportunity of a complete tumour removal.

PMID- 18042239
TI  - An observational study of first-line valproate monotherapy in focal epilepsy.
AB  - The objective of this multinational open-label, prospective study was to collect,
      under naturalistic conditions, data on the effectiveness and tolerability of
      first-line monotherapy with valproate in subjects newly or recently diagnosed
      with focal onset epilepsy. Patients were treated with sustained release sodium
      valproate. Seizure control and occurrence of adverse events were assessed after 6
      months. Around 1192 adults and 792 children were included. The mean daily
      valproate dose was 683 mg in children and 987 mg in adults. The retention rate at
      6 months was 90.0%. At this time, 77% of subjects were seizure free (83.7% of
      children and 72.7% of adults). Adverse events possibly related to treatment were
      observed in 10.2% of subjects, leading to treatment modification for 1.7%. The
      most common adverse events were weight gain, gastro-intestinal, neurological and
      skin disorders. Sustained release sodium valproate is effective and shows
      acceptable tolerability as first-line monotherapy in focal onset epilepsy.

PMID- 18042240
TI  - (99m)Tc-ethyl cysteinate dimer brain SPECT findings in early stage of dementia
      with Lewy bodies and Parkinson's disease patients: a correlation with
      neuropsychological tests.
AB  - We examined clinical presentations, neuropsychological findings, and perfusion
      patterns of (99m)Tc-ethyl cysteinate dimer (ECD) single photon emission computed
      tomography (SPECT) in patients with early stage dementia with Lewy bodies (DLB)
      (n = 17) and Parkinson's disease (PD) (n = 16), with age-matched healthy controls
      (n = 10). Seven paired regions of interest (ROIs) were drawn manually including
      inferior frontal, temporal, parietal, occipital, parieto-occipital junction,
      striatum and thalamus for semiquantitative measurement. Neuropsychological tests
      were applied for clinical correlation. The SPECT results showed significant
      hypoperfusion in DLB group in frontal, parietal, thalamus, temporal ROIs compared
      with controls (P < 0.01) whilst signals in temporal areas was significantly
      reduced compared with PD group (P < 0.05). Neuropsychological tests showed that
      DLB patients had deficits in mental manipulation, short-term memory, abstract
      thinking, drawing and semantic verbal fluencies (P < 0.05, compared with
      control). In addition, DLB group had lower scores than those with PD in mental
      manipulation, drawing and semantic verbal fluency (P < 0.05). Our study showed
      that even in early stages of DLB, neuropsychological and perfusion patterns were
      evident and may be different from PD group, despite they shared certain
      similarities both in neuropsychological and image findings compared with age
      matched controls.

PMID- 18042241
TI  - The frequency and nature of sleep disorders in a community-based population of
      patients with Parkinson's disease.
AB  - Sleep disturbances in Parkinson's disease (PD) are a common problem. The aim of
      this study was to detail the frequency and nature of sleep disorders in a
      representative population of PD patients. A recently identified prevalent
      population, consisting of 161 PD patients were used as a representative
      population. Twenty-seven of 122 (22%) patients were identified as having marked
      sleep disorders, with sleep fragmentation and nocturia being the most commonly
      reported problems. Sleep scores worsened with higher Hoehn and Yahr stages. Sleep
      disturbances are a relatively common complication of PD and worsen with
      increasing Hoehn and Yahr stage.

PMID- 18042242
TI  - Leukaemia inhibitory factor is over-expressed by ischaemic brain tissue
      concomitant with reduced plasma expression following acute stroke.
AB  - Leukaemia inhibitory factor (LIF) is a glycoprotein of the interleukin-6 family,
      which has potent pro-inflammatory properties and is involved in regulation of
      neuronal differentiation. We have previously identified its upregulation in gene
      microarrays following acute ischaemic stroke in man. LIF expression and
      localization was measured in human ischaemic stroke autopsy specimens, in a rat
      model of middle cerebral artery occlusion (MCAO) and in human foetal neural cell
      cultures following oxygen-glucose deprivation (OGD) by Western blotting and
      immunohistochemistry. Circulating LIF was determined in the plasma of patients in
      the hyper-acute stroke phase using a multiplex enzyme-linked-immunosorbent
      serologic assay system. Patients demonstrated an increase in LIF expression in
      peri-infarcted regions with localization in neurons and endothelial cells of
      microvessels surrounding the infarcted core. The rat MCAO model showed similar
      upregulation in neurons with a peak increase at 90 min. Circulating serum LIF
      expression was significantly decreased in the hyper-acute phase of stroke. Brain
      derived neurons and glia cultured in vitro demonstrated an increase in
      gene/protein and protein expression respectively following exposure to OGD.
      Increased LIF expression in peri-infarcted regions and sequestration from the
      peripheral circulation in acute stroke patients are characteristic of the
      pathobiological response to ischaemia and tissue damage.

PMID- 18042243
TI  - Spontaneous intracranial hypotension after labor without spinal intervention.
AB  - We present a 29-year-old woman admitted with severe postural headache after
      spontaneous term labor. Lactation ceased for the duration of headache. Magnetic
      resonance imaging (MRI) revealed dural thickening that is suggestive of
      spontaneous intracranial hypotension. CT-cisternography disclosed cervicodorsal
      dural leak. She was treated with a high-volume epidural blood patch (EBP) and her
      symptoms were relieved. Lactation returned to normal after EBP. She had normal
      findings on follow-up MRI examination at 6 months.

PMID- 18042244
TI  - Cerebral activity modulation by extradural motor cortex stimulation in
      Parkinson's disease: a perfusion SPECT study.
AB  - Extradural motor cortex stimulation (EMCS) has been proposed as alternative to
      deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD). Its
      mechanisms of action are still unclear. Neuroimaging evidenced motor cortical
      dysfunction in PD that can be reversed by therapy. We performed left hemisphere
      EMCS surgery in six advanced PD patients fulfilling CAPSIT criteria for DBS with
      the exception of age >70 years. After 6 months, we measured regional cerebral
      blood flow (rCBF) at rest with SPECT and Tc-99m cysteinate dimer bicisate off
      medication with stimulator off and on. Clinical assessment included Unified
      Parkinson's Disease Rating Scale part II and III, Abnormal Involuntary Movement
      Scale and mean dopaminergic medication dosage. We used statistical parametric
      mapping for imaging data analysis. Clinically we observed no mean changes in
      motor scales, although blinded evaluation revealed some benefit in individual
      patients. We found significant rCBF decrements in the pre-central gyrus, pre
      motor cortex and caudate nucleus bilaterally, left prefrontal areas and right
      thalamus. Perfusion increments were found in cerebellum bilaterally. EMCS
      determined significant modulation of neuronal activity within the cortico-basal
      ganglia-thalamo-cortical motor loop in our cohort of advanced PD patients.
      However, these effects were paralleled by mild and variable clinical efficacy.

PMID- 18042245
TI  - Constant dopaminergic stimulation by transdermal delivery of dopaminergic drugs:
      a new treatment paradigm in Parkinson's disease.
AB  - Current dopaminergic therapies for the treatment of Parkinson's disease are
      associated with the development of long-term motor complications. Abnormal
      pulsatile stimulation of dopamine receptors is thought to underlie the
      development of motor complications. There is thus a need for therapies that mimic
      the normal physiological state more closely by resulting in constant dopaminergic
      stimulation (CDS). Several studies support the hypothesis that CDS can reverse
      levodopa-induced motor complications. Other potential benefits of CDS include
      alleviating nocturnal disturbances, minimizing daytime sleepiness, avoiding
      priming for motor fluctuations and dyskinesia, preventing the development of
      gastrointestinal dysfunction and reducing the risk of developing psychosis or
      behavioural disturbances. Continuous infusion of dopaminergic therapies is
      impractical for the routine treatment of large numbers of patients. Although
      catechol-O-methyltransferase inhibitors or sustained-release preparations of
      levodopa may be beneficial, they do not entirely eliminate pulsatile stimulation
      of dopamine receptors. A new dopamine agonist (rotigotine), delivered over 24 h
      by a once-daily transdermal patch, has been investigated in several clinical
      trials. Continuous delivery of rotigotine has been shown to provide 'true' CDS in
      animal models. The potential of true CDS therapy to prevent or reduce long-term
      motor and non-motor complications requires investigation in appropriately
      designed clinical trials.

PMID- 18042246
TI  - A profile of the residues in the second extracellular loop that are critical for
      ligand recognition of human prostacyclin receptor.
AB  - The residues in the second extracellular loop (eLP2) of the prostanoid receptors,
      which are important for specific ligand recognition, were previously predicted in
      our earlier studies of the thromboxane A2 receptor (TP) using a combination of
      NMR spectroscopy and recombinant protein approaches. To further test this
      hypothesis, another prostanoid receptor, the prostacyclin receptor (IP), which
      has opposite biological characteristics to that of TP, was used as a model for
      these studies. A set of recombinant human IPs with site-directed mutations at the
      nonconserved eLP2 residues were constructed using an Ala-scanning approach, and
      then expressed in HEK293 and COS-7 cells. The expression levels of the
      recombinant receptors were six-fold higher in HEK293 cells than in COS-7 cells.
      The residues important for ligand recognition and binding within the N-terminal
      segment (G159, Q162, and C165) and the C-terminal segment (L172, R173, M174, and
      P179) of IP eLP2 were identified by mutagenesis analyses. The molecular
      mechanisms for the specific ligand recognition of IP were further demonstrated by
      specific site-directed mutagenesis using different amino acid residues with
      unique chemical properties for the key residues Q162, L172, R173, and M174. A
      comparison with the corresponding functional residues identified in TP eLP2
      revealed that three (Q162, R173, and M174) of the four residues are nonconserved,
      and these are proposed to be involved in specific ligand recognition. We discuss
      the importance of G159 and P179 in ligand recognition through configuration of
      the loop conformation is discussed. These studies have further indicated that
      characterization of the residues in the eLP2 regions for all eight prostanoid
      receptors could be an effective approach for uncovering the molecular mechanisms
      of the ligand selectivities of the G-protein-coupled receptors.

PMID- 18042247
TI  - Migration of mesenchymal cell fated to blastema is necessary for fish fin
      regeneration.
AB  - Urodeles and fish have higher regeneration ability in a variety of tissues and
      organs than do other vertebrate species including mammals. Though many studies
      have aimed at identifying the cellular and molecular basis for regeneration,
      relatively little is known about the detailed cellular behaviors and involved
      molecular basis. In the present study, a small molecule inhibitor was used to
      analyzed the role of phosphoinositide 3-kinase (PI3K) signaling during
      regeneration. We showed that the inhibitor disrupted the formation of blastema
      including the expression of characteristic genes. The failure of blastema
      formation was due to the impaired migration of mesenchymal cells to the distal
      prospective blastema region, although it had a little affect on cell cycle
      activation in mesenchymal cells. Moreover, we found that the epidermal remodeling
      including cell proliferation, distal cell migration and Akt phosphorylation was
      also affected by the inhibitor, implying a possible involvement of epidermis for
      proper formation of blastema. From these data, we propose a model in which
      distinct signals that direct the cell cycle activation, mesenchymal cell
      migration and epidermal remodeling coordinate together to accomplish the correct
      blastema formation and regeneration.

PMID- 18042248
TI  - Never perform laser treatment of skin tumors with clinical "EFG" criteria.
AB  - Laser treatment is a common procedure for the treatment of cosmetically troubling
      skin lesions but has the limitation that histopathologic diagnosis is usually not
      obtained prior to treatment. Laser treatment of melanomas with benign clinical
      features may delay or make more difficult the correct diagnosis of such tumors. A
      helpful tool to identify clinically innocent appearing melanomas is the "EFG"
      rule, summarizing the common clinical features as "elevated, firm skin lesions
      showing continuous growth". We report a 42-year-old woman who presented with a
      recurrent and metastatic melanoma after laser treatment of a tumor which was
      apparently clinically innocent and highlight the clinical features of such benign
      looking melanomas.

PMID- 18042249
TI  - Repigmentation of pretibial vitiligo with calcineurin inhibitors under occlusion.
AB  - Treatment of vitiligo is a challenge, especially in children. Recently, topical
      calcineurin inhibitors have been introduced in the management of vitiligo, but
      significant repigmentation is not achieved except on the face. Large pretibial
      lesions of a 15-year-old female with progressive vitiligo were treated twice
      daily over six months with 0.1% tacrolimus ointment on the right and 1%
      pimecrolimus cream on the left side without effect. Additional overnight
      occlusion with polyurethane and hydrocolloid foils during the following 18 months
      led to substantial repigmentation on both sides (tacrolimus-treated side, 88%
      repigmented area; pimecrolimus-treated side, 73%). Tacrolimus serum levels
      measured at four different time points did not exceed 1.8 ng/ml. This case report
      on a direct comparison of topical tacrolimus and pimecrolimus in vitiligo shows
      that on the shins considerable improvement could be induced with both agents only
      by additional long-term occlusion and that tacrolimus was somewhat more effective
      than pimecrolimus.

PMID- 18042250
TI  - Outcome survey of insect venom allergic patients with venom immunotherapy in a
      rural population.
AB  - BACKGROUND: Hymenoptera venom anaphylaxis is a frightening event that affects
      physical and psychical functioning. PATIENTS AND METHODS: Retrospective survey of
      182 Hymenoptera venom allergic patients living in a rural area using a
      questionnaire targeting on patients' satisfaction during therapy, fear of
      anaphylactic recurrences and changes in lifestyle before and after venom
      immunotherapy (VIT). Additionally, patients' self-assessment of quality of life,
      daily outdoor time and re-sting rate were recorded. RESULTS: 146 patients
      returned the questionnaire (58.9% male, 41.1% female, 25.3% honey bee allergic,
      67.8% wasp allergic, 41.1% re-sting rate, mean follow-up time 6.5 years).
      Measurement of the parameters fear, satisfaction and changes in lifestyle
      revealed a significant improvement after VIT. This correlated with the
      patients'self-assessment of quality of life,when 89.7% declared an improvement
      after VIT. Although the improvement was higher in patients with re-stings, also
      patients without re-stings clearly benefited from VIT. Interestingly, females
      were significantly more affected by Hymenoptera venom allergy than males,whereas
      both genders showed a similar improvement after VIT. CONCLUSIONS: Patients with
      Hymenoptera venom sting allergy significantly benefit from VIT in regard to both
      biological and psychological outcome. VIT should still be provided to all
      Hymenoptera venom allergic patients as standard of care.

PMID- 18042251
TI  - Rapid growth of malignant melanoma in pregnancy.
AB  - Malignant melanoma during pregnancy is a difficult problem as a variety of risks
      to both the mother and fetus must be weighed. We describe a rapidly progressive
      malignant melanoma diagnosed during pregnancy. There are no standarized
      guidelines for treatment; each case requires an individualized approach. We
      review the literature and present an algorithm to aid in approaching such
      patients.

PMID- 18042252
TI  - Muramylpeptide shedding modulates cell sensing of Shigella flexneri.
AB  - Bacterial infections trigger the activation of innate immunity through the
      interaction of pathogen-associated molecular patterns (PAMPs) with pattern
      recognition molecules (PRMs). The nucleotide-binding oligomerization domain (Nod)
      proteins are intracellular PRMs that recognize muramylpeptides contained in
      peptidoglycan (PGN) of bacteria. It is still unclear how Nod1 physically
      interacts with PGN, a structure internal to the Gram-negative bacterial envelope.
      To contribute to the understanding of this process, we demonstrate that, like
      Escherichia coli, Bordetella pertussis and Neisseria gonorrheae, the Gram
      negative pathogen Shigella spontaneously releases PGN fragments and that this
      process can be increased by inactivating either ampG or mppA, genes involved in
      PGN recycling. Both Shigella mutants, but especially the strain carrying the mppA
      deletion, trigger Nod1-mediated NF-kappaB activation to a greater extent than the
      wild-type strain. Likewise, muramylpeptides spontaneously shed by Shigella are
      able per se to trigger a Nod1-mediated response consistent with the relative
      amount. Finally, we found that qualitative changes in muramylpeptide shedding can
      alter in vivo host responses to Shigella infection. Our findings support the idea
      that muramylpeptides released by pathogens during infection could modulate the
      immune response through Nod proteins and thereby influence the outcome of
      disease.

PMID- 18042253
TI  - Clathrin-dependent trafficking of subtilase cytotoxin, a novel AB5 toxin that
      targets the endoplasmic reticulum chaperone BiP.
AB  - Subtilase cytotoxin (SubAB) is the prototype of a new family of AB5 cytotoxins
      produced by Shiga toxigenic Escherichia coli. Its cytotoxic activity is due to
      its capacity to enter cells and specifically cleave the endoplasmic reticulum
      (ER) chaperone BiP. However, its trafficking within target cells has not been
      investigated previously. In Vero cells, fluorescence colocalization with
      subcellular markers established that SubAB is trafficked from the cell surface to
      the ER via a retrograde pathway similar, but not identical, to those of Shiga
      toxin (Stx) and cholera toxin (Ctx), with their pathways converging at the Golgi.
      The clathrin inhibitor phenylarsine oxide prevented SubAB entry and BiP cleavage
      in SubAB-treated Vero, HeLa and N2A cells, while cholesterol depletion did not,
      demonstrating that, unlike either Stx or Ctx, SubAB internalization is
      exclusively clathrin-dependent.

PMID- 18042254
TI  - Parvovirus interference with intracellular signalling: mechanism of PKCeta
      activation in MVM-infected A9 fibroblasts.
AB  - Autonomous parvoviruses are strongly dependent on the phosphorylation of the
      major non-structural protein NS1 by members of the protein kinase C (PKC) family.
      Besides being accompanied with changes in the overall phosphorylation pattern of
      NS1 and acquiring new modifications at consensus PKC sites, ongoing minute virus
      of mice (MVM) infections lead to the appearance of new phosphorylated cellular
      protein species. This prompted us to investigate whether MVM actively interferes
      with phosphoinositol-dependent kinase (PDK)/PKC signalling. The activity,
      subcellular localization and phosphorylation status of the protein kinases PDK1,
      PKCeta and PKClambda were measured in A9 cells in the presence or absence of MVM
      infection. Parvovirus infection was found to result in activation of both PDK1
      and PKCeta, as evidenced by changes in their subcellular distribution and overall
      (auto)phosphorylation. We show evidence that activation of PKCeta by PDK1 is
      driven by atypical PKClambda. By modifying the hydrophobic motif of PKCeta,
      PKClambda appeared to control docking and consecutive phosphorylation of PKCeta's
      activation-loop by PDK1, a process that was inhibited in vivo in the presence of
      a dominant-negative PKClambda mutant.

PMID- 18042255
TI  - Pseudomonas aeruginosa virulence genes identified in a Dictyostelium host model.
AB  - The human pathogen Pseudomonas aeruginosa has been shown previously to use
      similar virulence factors when infecting mammalian hosts or Dictyostelium
      amoebae. Here we randomly mutagenized a clinical isolate of P. aeruginosa, and
      identified mutants with attenuated virulence towards Dictyostelium. These mutant
      strains also exhibited a strong decrease in virulence when infecting Drosophila
      and mice, confirming that P. aeruginosa makes use of similar virulence traits to
      confront these very different hosts. Further characterization of these bacterial
      mutants showed that TrpD is important for the induction of the quorum-sensing
      circuit, while PchH and PchI are involved in the induction of the type III
      secretion system. These results demonstrate the usefulness and the relevance of
      the Dictyostelium host model to identify and analyse new virulence genes in P.
      aeruginosa.

PMID- 18042256
TI  - Induction of lytic cycle replication of Kaposi's sarcoma-associated herpesvirus
      by herpes simplex virus type 1: involvement of IL-10 and IL-4.
AB  - Previously, we identified that both human herpesvirus 6 and human
      immunodeficiency virus type 1 Tat were important cofactors that activated lytic
      cycle replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Here, we
      further investigated the potential of herpes simplex virus type 1 (HSV-1) to
      influence KSHV replication. We demonstrated that HSV-1 was a potentially
      important factor in the pathogenesis of Kaposi's sarcoma, as determined by
      production of lytic phase mRNA transcripts, viral proteins and infectious viral
      particles in BCBL-1 cells. These results were further confirmed by an RNA
      interference experiment using small interfering RNA targeting KSHV ORF50 and a
      luciferase reporter assay testing ORF50 promoter-driven luciferase activity.
      Finally, we discovered that production of human interleukin-10 (IL-10) and IL-4
      partially contributed to HSV-1-induced KSHV replication. Our data present the
      first direct evidence that HSV-1 can activate KSHV lytic replication and suggest
      a role of HSV-1 in KSHV pathogenesis.

PMID- 18042257
TI  - Iron and fungal pathogenesis: a case study with Cryptococcus neoformans.
AB  - The acquisition of iron from mammalian hosts is an important aspect of infection
      because microbes must compete with the host for this nutrient and iron perception
      often regulates virulence factor expression. For example, iron levels are known
      to influence the elaboration of two major virulence factors, the polysaccharide
      capsule and melanin, in the pathogenic fungus Cryptococcus neoformans. This
      pathogen, which causes meningoencephalitis in immunocompromised people, acquires
      iron through the use of secreted reductants, cell surface reductases, a
      permease/ferroxidase uptake system and siderophore transporters. In addition, a
      master regulator, Cir1, integrates iron sensing with the expression of virulence
      factors, with growth at 37 degrees C and with signalling pathways that also
      influence virulence. The challenge ahead is to develop mechanistic views of the
      iron acquisition functions and regulatory schemes that operate when C. neoformans
      is in host tissue. Achieving these goals may contribute to an understanding of
      the notable predilection of the fungus for the mammalian central nervous system.

PMID- 18042258
TI  - Tick-borne encephalitis virus NS5 associates with membrane protein scribble and
      impairs interferon-stimulated JAK-STAT signalling.
AB  - Tick-borne encephalitis virus (TBEV) NS5 protein is a multifunctional RNA
      dependent RNA polymerase that is indispensable for viral replication. TBEV is
      considered to be highly neurovirulent and can cause lethal encephalitis. In this
      study, we demonstrate a novel interaction between TBEV NS5 and the PDZ protein
      scribble (hScrib) affecting interferon (IFN) type I and II mediated JAK-STAT
      signalling. The sequence of TBEV NS5 interacting with hScrib was identified using
      extensive site-directed mutagenesis analysis. Two consecutive mutations in the
      methyltransferase (MTase) domain of NS5 were found to disrupt binding to hScrib.
      Colocalization studies with hScrib demonstrated that TBEV NS5 was present at the
      plasma membrane of mammalian cells. To address the role of viral interference
      with the IFN response, NS5 proteins were expressed in IFN-stimulated cells. While
      TBEV NS5 substantially blocked phosphorylation of STAT1, a mutated NS5 protein
      defective in hScrib binding failed to inhibit JAK-STAT signalling correctly.
      Furthermore, hScrib knock-down resulted in re-localization of NS5 to
      intracellular locations and abrogated the impaired STAT1 phosphorylation. These
      results define the TBEV NS5 protein in concert with hScrib as an antagonist of
      the IFN response, by demonstrating a correlation between the association and JAK
      STAT interference.

PMID- 18042259
TI  - Baculovirus-mediated immediate-early gene expression and nuclear reorganization
      in human cells.
AB  - Baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), has
      the ability to transduce mammalian cell lines without replication. The general
      objective of this study was to detect the transcription and expression of viral
      immediate-early genes in human cells and to examine the interactions between
      viral components and subnuclear structures. Viral capsids were seen in large,
      discrete foci in nuclei of both dividing and non-dividing human cells.
      Concurrently, the transcription of viral immediate-early transregulator genes (ie
      1, ie-2) and translation of IE-2 protein were detected. Quantitative microscopy
      imaging and analysis showed that virus transduction altered the size of
      promyelocytic leukaemia nuclear bodies, which are suggested to be involved in
      replication and transcription of various viruses. Furthermore, altered
      distribution of the chromatin marker Draq5 and histone core protein (H2B) in
      transduced cells indicated that the virus was able to induce remodelling of the
      host cell chromatin. To conclude, this study shows that the non-replicative
      insect virus, baculovirus and its proteins can induce multiple changes in the
      cellular machinery of human cells.

PMID- 18042260
TI  - HIV-1 matrix protein p17 binds to monocytes and selectively stimulates MCP-1
      secretion: role of transcriptional factor AP-1.
AB  - HIV-1 matrix protein p17 activates a variety of cell responses which play a
      critical role in viral replication and infection. Its activity depends on the
      expression of p17 receptors (p17R) on the surface of target cells. Whether p17
      also plays a role in stimulating human monocytes, a major HIV-1 reservoir, is not
      known. Here we show that human monocytes constitutively express p17Rs and that
      p17 selectively triggers these cells to produce MCP-1. The effect of p17 on MCP-1
      expression was observed at the transcriptional level and was primarily dependent
      on the activation of the transcription factor AP-1. p17 increased the binding
      activity of AP-1 complexes in a time- and dose-dependent manner. Deletion of the
      AP-1 binding sites in the MCP-1 promoter resulted in the lack of p17-induced MCP
      1 transcription. In particular, the P3 binding site located between -69 and -63
      position seems to be essential to MCP-1 mRNA induction in p17-treated monocytes.
      An ever increasing amount of evidences shows a tight link between biologically
      dysregulated monocytes, AP-1 activation, MCP-1 release and HIV-1 pathogenesis.
      Overall our results suggest that p17 may play a critical role in the monocyte
      mediated inflammatory processes, which are suspected to be major precipitating
      events in AIDS-defining diseases.

PMID- 18042261
TI  - Elevated activity and microglial expression of myeloperoxidase in demyelinated
      cerebral cortex in multiple sclerosis.
AB  - Recent studies have revealed extensive cortical demyelination in patients with
      progressive multiple sclerosis (MS). Demyelination in gray matter lesions is
      associated with activation of microglia. Macrophages and microglia are known to
      express myeloperoxidase (MPO) and generate reactive oxygen species during myelin
      phagocytosis in the white matter. In the present study we examined the extent of
      microglial activation in the cerebral cortex and the relationship of microglial
      activation and MPO activity to cortical demyelination. Twenty-one cases of
      neuropathologically confirmed multiple sclerosis, with 34 cortical lesions, were
      used to assess microglial activation. HLA-DR immunolabeling of activated
      microglia was significantly higher in demyelinated MS cortex than control cortex
      and, within the MS cohort, was significantly greater within cortical lesions than
      in matched non-demyelinated areas of cortex. In homogenates of MS cortex,
      cortical demyelination was associated with significantly elevated MPO activity.
      Immunohistochemistry revealed MPO in CD68-positive microglia within cortical
      plaques, particularly toward the edge of the plaques, but not in microglia in
      adjacent non-demyelinated cortex. Cortical demyelination in MS is associated with
      increased activity of MPO, which is expressed by a CD68-positive subset of
      activated microglia, suggesting that microglial production of reactive oxygen
      species is likely to be involved in cortical demyelination.

PMID- 18042262
TI  - Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and
      Costello syndrome.
AB  - Cardio-facio-cutaneous (CFC) and Costello syndrome (CS) are congenital disorders
      with a significant clinical overlap. The recent discovery of heterozygous
      mutations in genes encoding components of the RAS-RAF-MAPK pathway in both CFC
      and CS suggested a similar underlying pathogenesis of these two disorders. While
      CFC is heterogeneous with mutations in BRAF, MAP2K1, MAP2K2 and KRAS, HRAS
      alterations are almost exclusively associated with CS. We carried out a
      comprehensive mutation analysis in 51 CFC-affected patients and 31 individuals
      with CS. Twelve different BRAF alterations were found in twenty-four patients
      with CFC (47.0%), two MAP2K1 mutations in five (9.8%) and two MAP2K2 sequence
      variations in three CFC-affected individuals (5.9%), whereas three patients had a
      KRAS alteration (5.9%). We identified four different missense mutations of HRAS
      in twenty-eight cases with CS (90.3%), while KRAS mutations were detected in two
      infants with a phenotype meeting criteria for CS (6.5%). In 14 informative
      families, we traced the parental origin of HRAS alterations and demonstrated
      inheritance of the mutated allele exclusively from the father, further confirming
      a paternal bias in the parental origin of HRAS mutations in CS. Careful clinical
      evaluation of patients with BRAF and MAP2K1/2 alterations revealed the presence
      of slight phenotypic differences regarding craniofacial features in MAP2K1- and
      MAP2K2-mutation positive individuals, suggesting possible genotype-phenotype
      correlations.

PMID- 18042263
TI  - Sotos syndrome caused by a paracentric inversion disrupting the NSD1 gene.

PMID- 18042264
TI  - Australia and New Zealand survey of glaucoma practice patterns.
AB  - BACKGROUND: To evaluate current glaucoma practices among consultant
      ophthalmologists in Australia and New Zealand. METHODS: A postal questionnaire of
      25 questions regarding current glaucoma practices and the use of antimetabolites
      and steroids in trabeculectomy surgery was sent to all practising Australian and
      New Zealand Fellows of the Royal Australian and New Zealand College of
      Ophthalmologists (as of June 2005). This paper looked at glaucoma practice
      patterns and consisted of questions on demographic data, the definition of
      glaucoma, intraocular pressure measurements, central corneal thickness,
      gonioscopy, optic disc assessment, preferred first-line glaucoma medications and
      laser trabeculoplasty. RESULTS: The overall response rate was 78% (627 out of
      808). Ninety-one per cent stated that they managed glaucoma of which 12%
      considered themselves as a glaucoma subspecialist. Eighty-two per cent of
      ophthalmologists defined glaucoma as an optic neuropathy and 66% measured the
      intraocular pressure themselves. Pachymetry was routinely measured by 37%. When
      performing gonioscopy, 56% did this (more than 50% of the time) but only 13%
      repeated it. Fifty-eight per cent assessed the optic disc by objective means and
      18% used this to follow glaucoma patients. Eighty-two per cent preferred a
      prostaglandin analogue as first-line treatment of primary open angle glaucoma and
      79% did less than 10 argon laser trabeculoplasties in 2004. CONCLUSIONS: This
      survey shows a wide range of glaucoma practice patterns among Australian and New
      Zealand ophthalmologists. Gonioscopy (initial and repeat) and objective
      assessment of the optic disc were poorly done.

PMID- 18042265
TI  - Daytime steady-state haemoglobin desaturation is a risk factor for overt stroke
      in children with sickle cell anaemia.
AB  - Haemoglobin (Hb) desaturation could increase the risk of stroke in sickle cell
      anaemia (SS) by perturbing endothelial function and limiting oxygen delivery to
      the brain. We performed a nested case-control study of the Dallas Newborn Cohort
      to determine whether daytime steady-state Hb desaturation was associated with
      overt stroke in children with SS. Cases had SS and overt ischaemic strokes.
      Controls had comparable genotypes but no overt stroke. Cases had lower prestroke
      steady-state pulse oximetry values (SpO(2)) than controls, and cases' SpO(2) fell
      even lower as the time to impending stroke decreased. The odds ratio for stroke
      was 1.32 for each 1% decrease in SpO(2). In conclusion, steady-state Hb
      desaturation is a risk factor for overt ischaemic stroke in children with SS.
      Decline in SpO(2) over time further increases this risk. Hb desaturation is
      easily measured, potentially modifiable, and could be used to identify children
      with SS at increased risk of stroke.

PMID- 18042266
TI  - Thalidomide and bowel perforation: four cases in one hospital.

PMID- 18042267
TI  - Association between folate-metabolizing pathway polymorphism and non-Hodgkin
      lymphoma.
AB  - Polymorphisms in the genes coding folate-metabolizing enzymes affect the risk of
      some forms of cancer. We investigated the association between these polymorphisms
      and non-Hodgkin lymphoma (NHL) risk in a population-based study (583 cases and
      1700 controls). The MTHFR 677TT and CT genotypes were associated with reduced
      risk for NHL [odds ratios (OR) = 0.79; 95% confidence intervals (CI) = 0.65-0.98
      for 677CT and 0.61; 0.45-0.82 for 677TT] and diffuse large B-cell lymphoma
      (DLBCL) (OR = 0.68; 0.51-0.88 for 677CT; OR = 0.56; 0.38-0.83 for 677TT). The
      MTHFR 1298CC genotype was associated with increased risk for NHL (OR = 1.71; 1.07
      2.75) and T-cell lymphoma (OR = 3.05; 1.53-6.11). The MTRR 66GG genotype was
      associated with increased risk for DLBCL (OR = 1.56; 1.03-2.38) and the TYMS 2R2R
      genotype was associated with increased risk for T-cell lymphoma (OR = 2.83; 1.33
      6.01). Using subjects with 3RG3RG as a reference group, TYMS 2R2R was associated
      with increased risk for T-cell lymphoma (OR = 2.46; 1.04-5.79). Interestingly, we
      observed a reduced association between the TYMS 2R3RG genotype and DLBCL (OR =
      0.61; 0.38-0.99). These results suggest that MTHFR, MTRR and TYMS polymorphisms
      may play a significant role in the risk for NHL.

PMID- 18042268
TI  - Images in haematology. Human babesiosis.

PMID- 18042269
TI  - Distribution of etiologies in patients above and below age 45 with first-ever
      ischemic stroke.
AB  - BACKGROUND: There is limited information about distribution of etiologies of
      ischemic stroke in different age groups. MATERIALS AND METHODS: In this study, we
      applied the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification
      in 87 patients aged < or = 45, and in 347 patients aged 46-60 years with first
      ever ischemic stroke in order to follow the distribution of stroke etiologies in
      different age groups. RESULTS: Traditional risk factors, except smoking and
      atrial fibrillation, were more frequent in older patients. The most frequent
      etiologies in the younger stroke patients (aged < or = 45) were 'other' than
      routine causes (26.4%), cardioembolism (22.4%) and 'idiopathic' strokes (20.7%),
      when no cause was found. In older patients (aged 46-60), small vessel disease
      (25.1%) and cardioembolism (22.2%) were the most frequent etiologies of stroke.
      CONCLUSIONS: In stroke patients below the age of 45, the TOAST classification
      should be expanded to better classify the wide diversity of stroke etiologies.
      The relatively low frequency of routine stroke etiologies in patients aged < or =
      45 can be explained by the significantly lower prevalence of traditional risk
      factors in these patients. In patients 46-60 years old, the TOAST classification
      is adequate in the characterization of ischemic stroke etiologies.

PMID- 18042270
TI  - An extension of the regression of offspring on mid-parent to test for association
      and estimate locus-specific heritability: the revised ROMP method.
AB  - The Regression of Offspring on Mid-Parent (ROMP) method is a test of association
      between a quantitative trait and a candidate locus. ROMP estimates the trait
      heritability and the heritability attributable to a locus and requires genotyping
      the offspring only. In this study, the theory underlying ROMP was revised
      (ROMP(rev)) and extended. Computer simulations were used to determine the type I
      error and power of the test of association, and the accuracy of the locus
      specific heritability estimate. The ROMP(rev) test had good power at the 5%
      significance level with properly controlled type I error. Locus-specific
      heritability estimates were, on average, close to simulated values. For non-zero
      locus-specific heritability, the proposed standard error was downwardly biased,
      yielding reduced coverage of 95% confidence intervals. A bootstrap approach with
      proper coverage is suggested as a second step for loci of interest. ROMP(rev) was
      applied to a study of cardiovascular-related traits to illustrate its use. An
      association between polymorphisms within the fibrinogen gene cluster and plasma
      fibrinogen was detected (p < 0.005) that accounted for 29% of the estimated
      fibrinogen heritability. The ROMP(rev) method provides a computationally fast and
      simple way of testing for association and obtaining accurate estimates of locus
      specific heritability while minimizing the genotyping required.

PMID- 18042271
TI  - A clinically integrated curriculum in evidence-based medicine for just-in-time
      learning through on-the-job training: the EU-EBM project.
AB  - BACKGROUND: Over the last years key stake holders in the healthcare sector have
      increasingly recognised evidence based medicine (EBM) as a means to improving the
      quality of healthcare. However, there is considerable uncertainty about the best
      way to disseminate basic knowledge of EBM. As a result, huge variation in EBM
      educational provision, setting, duration, intensity, content, and teaching
      methodology exists across Europe and worldwide. Most courses for health care
      professionals are delivered outside the work context ('stand alone') and lack
      adaptation to the specific needs for EBM at the learners' workplace. Courses with
      modern 'adaptive' EBM teaching that employ principles of effective continuing
      education might fill that gap. We aimed to develop a course for post-graduate
      education which is clinically integrated and allows maximum flexibility for
      teachers and learners. METHODS: A group of experienced EBM teachers, clinical
      epidemiologists, clinicians and educationalists from institutions from eight
      European countries participated. We used an established methodology of curriculum
      development to design a clinically integrated EBM course with substantial
      components of e-learning. An independent European steering committee provided
      input into the process. RESULTS: We defined explicit learning objectives about
      knowledge, skills, attitudes and behaviour for the five steps of EBM. A handbook
      guides facilitator and learner through five modules with clinical and e-learning
      components. Focussed activities and targeted assignments round off the learning
      process, after which each module is formally assessed. CONCLUSION: The course is
      learner-centred, problem-based, integrated with activities in the workplace and
      flexible. When successfully implemented, the course is designed to provide just
      in-time learning through on-the-job-training, with the potential for teaching and
      learning to directly impact on practice.

PMID- 18042272
TI  - Identification of DNA-binding proteins using support vector machines and
      evolutionary profiles.
AB  - BACKGROUND: Identification of DNA-binding proteins is one of the major challenges
      in the field of genome annotation, as these proteins play a crucial role in gene
      regulation. In this paper, we developed various SVM modules for predicting DNA
      binding domains and proteins. All models were trained and tested on multiple
      datasets of non-redundant proteins. RESULTS: SVM models have been developed on
      DNAaset, which consists of 1153 DNA-binding and equal number of non DNA-binding
      proteins, and achieved the maximum accuracy of 72.42% and 71.59% using amino acid
      and dipeptide compositions, respectively. The performance of SVM model improved
      from 72.42% to 74.22%, when evolutionary information in form of PSSM profiles was
      used as input instead of amino acid composition. In addition, SVM models have
      been developed on DNAset, which consists of 146 DNA-binding and 250 non-binding
      chains/domains, and achieved the maximum accuracy of 79.80% and 86.62% using
      amino acid composition and PSSM profiles. The SVM models developed in this study
      perform better than existing methods on a blind dataset. CONCLUSION: A highly
      accurate method has been developed for predicting DNA-binding proteins using SVM
      and PSSM profiles. This is the first study in which evolutionary information in
      form of PSSM profiles has been used successfully for predicting DNA-binding
      proteins. A web-server DNAbinder has been developed for identifying DNA-binding
      proteins and domains from query amino acid sequences
      http://www.imtech.res.in/raghava/dnabinder/.

PMID- 18042273
TI  - Evaluation and validation of candidate endogenous control genes for real-time
      quantitative PCR studies of breast cancer.
AB  - BACKGROUND: Real-time quantitative PCR (RQ-PCR) forms the basis of many breast
      cancer biomarker studies and novel prognostic assays, paving the way towards
      personalised cancer treatments. Normalisation of relative RQ-PCR data is required
      to control for non-biological variation introduced during sample preparation.
      Endogenous control (EC) genes, used in this context, should ideally be expressed
      constitutively and uniformly across treatments in all test samples. Despite
      widespread recognition that the accuracy of the normalised data is largely
      dependent on the reliability of the EC, there are no reports of the systematic
      validation of genes commonly used for this purpose in the analysis of gene
      expression by RQ-PCR in primary breast cancer tissues. The aim of this study was
      to identify the most suitable endogenous control genes for RQ-PCR analysis of
      primary breast tissue from a panel of eleven candidates in current use. Oestrogen
      receptor alpha (ESR1) was used a target gene to compare the effect of choice of
      EC on the estimate of gene quantity. RESULTS: The expression and validity of
      candidate ECs (GAPDH, TFRC, ABL, PPIA, HPRT1, RPLP0, B2M, GUSB, MRPL19, PUM1 and
      PSMC4) was determined in 6 benign and 21 malignant primary breast cancer tissues.
      Gene expression data was analysed using two different statistical models. MRPL19
      and PPIA were identified as the most stable and reliable EC genes, while GUSB,
      RPLP0 and ABL were least stable. There was a highly significant difference in
      variance between ECs. ESR1 expression was appreciably higher in malignant
      compared to benign tissues and there was a significant effect of EC on the
      magnitude of the error associated with the relative quantity of ESR1. CONCLUSION:
      We have validated two endogenous control genes, MRPL19 and PPIA, for RQ-PCR
      analysis of gene expression in primary breast tissue. Of the genes in current use
      in this field, the above combination offers increased accuracy and resolution in
      the quantitation of gene expression data, facilitating the detection of smaller
      changes in gene expression than otherwise possible. The combination identified
      here is a good candidate for use as a two-gene endogenous control in a broad
      spectrum of future research and diagnostic applications in breast cancer.

PMID- 18042274
TI  - Age-related subproteomic analysis of mouse liver and kidney peroxisomes.
AB  - BACKGROUND: Despite major recent advances in the understanding of peroxisomal
      functions and how peroxisomes arise, only scant information is available
      regarding this organelle in cellular aging. The aim of this study was to
      characterize the changes in the protein expression profile of aged versus young
      liver and kidney peroxisome-enriched fractions from mouse and to suggest possible
      mechanisms underlying peroxisomal aging. Peroxisome-enriched fractions from 10
      weeks, 18 months and 24 months C57bl/6J mice were analyzed by quantitative
      proteomics. RESULTS: Peroxisomal proteins were enriched by differential and
      density gradient centrifugation and proteins were separated by two-dimensional
      electrophoresis (2-DE), quantified and identified by mass spectrometry (MS). In
      total, sixty-five proteins were identified in both tissues. Among them, 14
      proteins were differentially expressed in liver and 21 proteins in kidney. The
      eight proteins differentially expressed in both tissues were involved in beta
      oxidation, alpha-oxidation, isoprenoid biosynthesis, amino acid metabolism, and
      stress response. Quantitative proteomics, clustering methods, and prediction of
      transcription factors, all indicated that there is a decline in protein
      expression at 18 months and a recovery at 24 months. CONCLUSION: These results
      indicate that some peroxisomal proteins show a tissue-specific functional
      response to aging. This response is probably dependent on their differential
      regeneration capacity. The differentially expressed proteins could lead several
      cellular effects: such as alteration of fatty acid metabolism that could alert
      membrane protein functions, increase of the oxidative stress and contribute to
      decline in bile salt synthesis. The ability to detect age-related variations in
      the peroxisomal proteome can help in the search for reliable and valid aging
      biomarkers.

PMID- 18042275
TI  - Web GIS in practice V: 3-D interactive and real-time mapping in Second Life.
AB  - This paper describes technologies from Daden Limited for geographically mapping
      and accessing live news stories/feeds, as well as other real-time, real-world
      data feeds (e.g., Google Earth KML feeds and GeoRSS feeds) in the 3-D virtual
      world of Second Life, by plotting and updating the corresponding Earth location
      points on a globe or some other suitable form (in-world), and further linking
      those points to relevant information and resources. This approach enables users
      to visualise, interact with, and even walk or fly through, the plotted data in 3
      D. Users can also do the reverse: put pins on a map in the virtual world, and
      then view the data points on the Web in Google Maps or Google Earth. The
      technologies presented thus serve as a bridge between mirror worlds like Google
      Earth and virtual worlds like Second Life. We explore the geo-data display
      potential of virtual worlds and their likely convergence with mirror worlds in
      the context of the future 3-D Internet or Metaverse, and reflect on the potential
      of such technologies and their future possibilities, e.g. their use to develop
      emergency/public health virtual situation rooms to effectively manage emergencies
      and disasters in real time. The paper also covers some of the issues associated
      with these technologies, namely user interface accessibility and individual
      privacy.

PMID- 18042276
TI  - Mortality associated with HIV-1, HIV-2, and HTLV-I single and dual infections in
      a middle-aged and older population in Guinea-Bissau.
AB  - BACKGROUND: In Guinea-Bissau HIV-1, HIV-2, and HTLV-I are prevalent in the
      general population. The natural history of HIV/HTLV-I single and dual infections
      has not been fully elucidated in this population. Previous studies have shown
      that combinations of these infections are more common in older women than in men.
      The present study compares mortality associated with HIV-1, HIV-2, and HTLV-I
      single and dual infections in individuals over 35 years of age within an urban
      community-based cohort in Guinea-Bissau. RESULTS: A total of 2,839 and 1,075
      individuals were included in the HIV and HTLV-I mortality analyses respectively.
      Compared with HIV-negative individuals, adjusted mortality rate ratios (MRRs)
      were 4.9 (95% confidence interval (CI): 2.3, 10.4) for HIV-1, 1.8 (95%CI: 1.5,
      2.3) for HIV-2, and 5.9 (2.4, 14.3) for HIV-1/HIV-2 dual infections. MRR for HTLV
      I-positive compared with HTLV-I-negative individuals was 1.7 (1.1, 2.7).
      Excluding all HIV-positive individuals from the analysis, the HTLV-I MRR was 2.3
      (1.3, 3.8). The MRR of HTLV-I/HIV-2 dually infected individuals was 1.7 (0.7,
      4.3), compared with HIV/HTLV-I-negative individuals. No statistically significant
      differences were found in retrovirus-associated mortality between men and women.
      CONCLUSION: HIV-1-associated excess mortality was low compared with community
      studies from other parts of Africa, presumably because this population was older
      and the introduction of HIV-1 into the community recent. HIV-2 and HTLV-I
      associated mortality was 2-fold higher than the mortality in uninfected
      individuals. We found no significant differences between the mortality risk for
      HIV-2 and HTLV-I single infection, respectively, and HIV-2/HTLV-I dual infection.
      The higher prevalence of retroviral dual infections in older women is not
      explained by differential retrovirus-associated mortality for men and women.

PMID- 18042277
TI  - Cross-sectional analysis of adverse outcomes in 1,029 pregnancies of Afro
      Caribbean women in Trinidad with and without systemic lupus erythematosus.
AB  - The objective of the study was to examine pregnancy outcomes in women with
      systemic lupus erythematosus (SLE) and population controls in Trinidad. We
      performed a cross-sectional analysis of adverse outcomes in pregnancies of Afro
      Caribbean women with SLE and without SLE. One hundred and twenty-two female adult
      cases of SLE and 203 neighbourhood age-matched women without SLE were interviewed
      concerning details of their reproductive history, and the anticardiolipin
      antibody (ACL) status was established for women with SLE. A total of 1,029
      pregnancies were reported (356 by women with SLE, 673 by women without SLE). In
      women with > or = 1 pregnancy the total number of pregnancies was similar in
      women with a diagnosis of SLE and women without; however, a lower proportion of
      women with SLE had ever been pregnant compared with women without SLE (80% versus
      91%, P = 0.002). In multivariate logistic regression analyses adjusted for
      maternal age, district of residence, pregnancy order and smoking, SLE pregnancies
      were more than twice as likely to end in foetal death than non-SLE pregnancies
      (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2-4.7). This effect was
      driven by a large increase in the odds of stillbirth (OR, 8.5; 95% CI, 2.5-28.8).
      The odds of early miscarriage (OR, 1.4; 95% CI, 0.6-3.1) and of mid-trimester
      miscarriage (OR, 1.9; 95% CI, 0.4-9.5) were higher, but were not statistically
      significantly different, in SLE pregnancies than in non-SLE pregnancies. The odds
      of ectopic pregnancy (OR, 7.5; 95% CI, 0.9-62.5) and of preterm birth (OR, 3.4;
      95% CI, 1.2-10.0) were higher in SLE pregnancies conceived after diagnosis than
      in non-SLE pregnancies. There was no evidence of raised levels of IgG or IgM ACL
      among the majority (93/97 women, 96%) of SLE cases who reported sporadic mid
      trimester miscarriage or stillbirth, although there was evidence of high levels
      of IgM and IgG ACL among women reporting three or more miscarriages and three
      consecutive miscarriages, and of raised IgG ACL among those experiencing ectopic
      pregnancy. In conclusion, we found evidence for a large increase in risk of
      stillbirth in the pregnancies of Afro-Caribbean Trinidadian women with SLE (not
      accounted for by high ACL status). There was some evidence of an increased risk
      of preterm delivery and ectopic pregnancy in pregnancies conceived after a
      diagnosis of maternal SLE.

PMID- 18042278
TI  - Successful removal of a telephone cable, a foreign body through the urethra into
      the bladder: a case report.
AB  - The variety of foreign bodies inserted into or externally attached to the
      genitourinary tract defies imagination and includes all types of objects. The
      frequency of such cases renders these an important addition to the diseases of
      the genitourinary organs. The most common motive associated with the insertion of
      foreign bodies into the genitourinary tract is sexual or erotic in nature. In
      adults this is commonly caused by the insertion of objects used for masturbation
      and is frequently associated with mental health disorders. We report a case of
      insertion of telephone cable wire into the urethra. Our case highlights the
      importance of good history, clinical examination, relevant radiological
      investigation and simple measures to solve the problem.

PMID- 18042279
TI  - Comparative analysis of cyanobacterial superoxide dismutases to discriminate
      canonical forms.
AB  - BACKGROUND: Superoxide dismutases (SOD) are ubiquitous metalloenzymes that
      catalyze the disproportion of superoxide to peroxide and molecular oxygen through
      alternate oxidation and reduction of their metal ions. In general, SODs are
      classified into four forms by their catalytic metals namely; FeSOD, MnSOD,
      Cu/ZnSOD and NiSOD. In addition, a cambialistic form that uses Fe/Mn in its
      active site also exists. Cyanobacteria, the oxygen evolving photosynthetic
      prokaryotes, produce reactive oxygen species that can damage cellular components
      leading to cell death. Thus, the co-evolution of an antioxidant system was
      necessary for the survival of photosynthetic organisms with SOD as the initial
      enzyme evolved to alleviate the toxic effect. Cyanobacteria represent the first
      oxygenic photoautotrophs and their SOD sequences available in the databases lack
      clear annotation. Hence, the present study focuses on structure and sequence
      pattern of subsets of cyanobacterial superoxide dismutases. RESULT: The sequence
      conservation and structural analysis of Fe (Thermosynechococcus elongatus BP1)
      and MnSOD (Anabaena sp. PCC7120) reveal the sharing of N and C terminal domains.
      At the C terminal domain, the metal binding motif in cyanoprokaryotes is DVWEHAYY
      while it is D-X-[WF]-E-H-[STA]-[FY]-[FY] in other pro- and eukaryotes. The
      cyanobacterial FeSOD differs from MnSOD at least in three ways viz. (i) FeSOD has
      a metal specific signature F184X3A188Q189.......T280......F/Y303 while, in Mn it
      is R184X3G188G189......G280......W303, (ii) aspartate ligand forms a hydrogen
      bond from the active site with the outer sphere residue of W243 in Fe where as it
      is Q262 in MnSOD; and (iii) two unique lysine residues at positions 201 and 255
      with a photosynthetic role, found only in FeSOD. Further, most of the
      cyanobacterial Mn metalloforms have a specific transmembrane hydrophobic pocket
      that distinguishes FeSOD from Mn isoform. Cyanobacterial Cu/ZnSOD has a copper
      domain and two different signatures G-F-H-[ILV]-H-x-[NGT]-[GPDA]-[SQK]-C and G
      [GA]-G-G-[AEG]-R-[FIL]-[AG]-C-G, while Ni isoform has an nickel containing SOD
      domain containing a Ni-hook HCDGPCVYDPA. CONCLUSION: The present analysis
      unravels the ambiguity among cyanobacterial SOD isoforms. NiSOD is the only SOD
      found in lower forms; whereas, Fe and Mn occupy the higher orders of
      cyanobacteria. In conclusion, cyanobacteria harbor either Ni alone or a
      combination of Fe and Ni or Fe and Mn as their catalytic active metal while Cu/Zn
      is rare.

PMID- 18042280
TI  - Clusters of orthologous genes for 41 archaeal genomes and implications for
      evolutionary genomics of archaea.
AB  - BACKGROUND: An evolutionary classification of genes from sequenced genomes that
      distinguishes between orthologs and paralogs is indispensable for genome
      annotation and evolutionary reconstruction. Shortly after multiple genome
      sequences of bacteria, archaea, and unicellular eukaryotes became available, an
      attempt on such a classification was implemented in Clusters of Orthologous
      Groups of proteins (COGs). Rapid accumulation of genome sequences creates
      opportunities for refining COGs but also represents a challenge because of error
      amplification. One of the practical strategies involves construction of refined
      COGs for phylogenetically compact subsets of genomes. RESULTS: New Archaeal
      Clusters of Orthologous Genes (arCOGs) were constructed for 41 archaeal genomes
      (13 Crenarchaeota, 27 Euryarchaeota and one Nanoarchaeon) using an improved
      procedure that employs a similarity tree between smaller, group-specific
      clusters, semi-automatically partitions orthology domains in multidomain
      proteins, and uses profile searches for identification of remote orthologs. The
      annotation of arCOGs is a consensus between three assignments based on the COGs,
      the CDD database, and the annotations of homologs in the NR database. The 7538
      arCOGs, on average, cover approximately 88% of the genes in a genome compared to
      a approximately 76% coverage in COGs. The finer granularity of ortholog
      identification in the arCOGs is apparent from the fact that 4538 arCOGs
      correspond to 2362 COGs; approximately 40% of the arCOGs are new. The archaeal
      gene core (protein-coding genes found in all 41 genome) consists of 166 arCOGs.
      The arCOGs were used to reconstruct gene loss and gene gain events during
      archaeal evolution and gene sets of ancestral forms. The Last Archaeal Common
      Ancestor (LACA) is conservatively estimated to possess 996 genes compared to 1245
      and 1335 genes for the last common ancestors of Crenarchaeota and Euryarchaeota,
      respectively. It is inferred that LACA was a chemoautotrophic hyperthermophile
      that, in addition to the core archaeal functions, encoded more idiosyncratic
      systems, e.g., the CASS systems of antivirus defense and some toxin-antitoxin
      systems. CONCLUSION: The arCOGs provide a convenient, flexible framework for
      functional annotation of archaeal genomes, comparative genomics and evolutionary
      reconstructions. Genomic reconstructions suggest that the last common ancestor of
      archaea might have been (nearly) as advanced as the modern archaeal
      hyperthermophiles. ArCOGs and related information are available at:
      ftp://ftp.ncbi.nih.gov/pub/koonin/arCOGs/.

PMID- 18042281
TI  - Effect of spatial resolution on cluster detection: a simulation study.
AB  - BACKGROUND: Aggregation of spatial data is intended to protect privacy, but some
      effects of aggregation on spatial methods have not yet been quantified. METHODS:
      We generated 3,000 spatial data sets and evaluated power of detection at 12
      different levels of aggregation using the spatial scan statistic implemented in
      SaTScan v6.0. RESULTS: Power to detect clusters decreased from nearly 100% when
      using exact locations to roughly 40% at the coarsest level of spatial resolution.
      CONCLUSION: Aggregation has the potential for obfuscation.

PMID- 18042282
TI  - Characterization of the innate immune response to chronic aspiration in a novel
      rodent model.
AB  - BACKGROUND: Although chronic aspiration has been associated with several
      pulmonary diseases, the inflammatory response has not been characterized. A novel
      rodent model of chronic aspiration was therefore developed in order to
      investigate the resulting innate immune response in the lung. METHODS: Gastric
      fluid or normal saline was instilled into the left lung of rats (n = 48) weekly
      for 4, 8, 12, or 16 weeks (n = 6 each group). Thereafter, bronchoalveolar lavage
      specimens were collected and cellular phenotypes and cytokine concentrations of
      IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and
      TGF-beta were determined. RESULTS: Following the administration of gastric fluid
      but not normal saline, histologic specimens exhibited prominent evidence of giant
      cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis.
      Bronchoalveolar lavage specimens from the left (treated) lungs exhibited
      consistently higher macrophages and T cells with an increased CD4:CD8 T cell
      ratio after treatment with gastric fluid compared to normal saline. The
      concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were
      increased in bronchoalveolar lavage specimens following gastric fluid aspiration
      compared to normal saline. CONCLUSION: This represents the first description of
      the pulmonary inflammatory response that results from chronic aspiration.
      Repetitive aspiration events can initiate an inflammatory response consisting of
      macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL
      1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of
      gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis,
      these findings further support an association between chronic aspiration and
      pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and
      asthma.

PMID- 18042283
TI  - Systematic analysis of mRNA 5' coding sequence incompleteness in Danio rerio: an
      automated EST-based approach.
AB  - BACKGROUND: All standard methods for cDNA cloning are affected by a potential
      inability to effectively clone the 5' region of mRNA. The aim of this work was to
      estimate mRNA open reading frame (ORF) 5' region sequence completeness in the
      model organism Danio rerio (zebrafish). RESULTS: We implemented a novel automated
      approach (5'_ORF_Extender) that systematically compares available expressed
      sequence tags (ESTs) with all the zebrafish experimentally determined mRNA
      sequences, identifies additional sequence stretches at 5' region and scans for
      the presence of all conditions needed to define a new, extended putative ORF. Our
      software was able to identify 285 (3.3%) mRNAs with putatively incomplete ORFs at
      5' region and, in three example cases selected (selt1a, unc119.2, nppa), the
      extended coding region at 5' end was cloned by reverse transcription-polymerase
      chain reaction (RT-PCR). CONCLUSION: The implemented method, which could also be
      useful for the analysis of other genomes, allowed us to describe the relevance of
      the "5' end mRNA artifact" problem for genomic annotation and functional genomic
      experiment design in zebrafish.

PMID- 18042284
TI  - Determinants of sexual activity and its relation to cervical cancer risk among
      South African women.
AB  - BACKGROUND: Invasive cervical cancer is the commonest cause of cancer morbidity
      and mortality in South African women. This study provides information on adult
      women's sexual activity and cervical cancer risk in South Africa. METHODS: The
      data were derived from a case-control study of hormonal contraceptives and
      cervical cancer risk. Information on age of sexual debut and number of lifetime
      sexual partners was collected from 524 incident cases and 1541 hospital controls.
      Prevalence ratios and adjusted prevalence ratios were utilised to estimate risk
      in exposures considered common. Crude and adjusted relative risks were estimated
      where the outcome was uncommon, using multiple logistic regression analysis.
      RESULTS: The median age of sexual debut and number of sexual partners was 17
      years and 2 respectively. Early sexual debut was associated with lower education,
      increased number of life time partners and alcohol use. Having a greater number
      of sexual partners was associated with younger sexual debut, being black, single,
      higher educational levels and alcohol use. The adjusted odds ratio for sexual
      debut < 16 years and >/= 4 life-time sexual partners and cervical cancer risk
      were 1.6 (95% CI 1.2 - 2.2) and 1.7 (95% CI 1.2 - 2.2), respectively. CONCLUSION:
      Lower socio-economic status, alcohol intake, and being single or black, appear to
      be determinants of increased sexual activity in South African women. Education
      had an ambiguous effect. As expected, cervical cancer risk is associated with
      increased sexual activity. Initiatives to encourage later commencement of sex,
      and limiting the number of sexual partners would have a favourable impact on risk
      of cancer of the cervix and other sexually transmitted infections.

PMID- 18042285
TI  - Production of single chain Fab (scFab) fragments in Bacillus megaterium.
AB  - BACKGROUND: The demand on antigen binding reagents in research, diagnostics and
      therapy raises questions for novel antibody formats as well as appropriate
      production systems. Recently, the novel single chain Fab (scFab) antibody format
      combining properties of single chain Fv (scFv) and Fab fragments was produced in
      the Gram-negative bacterium Escherichia coli. In this study we evaluated the Gram
      positive bacterium Bacillus megaterium for the recombinant production of scFab
      and scFvs in comparison to E. coli. RESULTS: The lysozyme specific D1.3 scFab was
      produced in B. megaterium and E. coli. The total yield of the scFab after
      purification obtained from the periplasmic fraction and culture supernatant of E.
      coli was slightly higher than that obtained from culture supernatant of B.
      megaterium. However, the yield of functional scFab determined by analyzing the
      antigen binding activity was equally in both production systems. Furthermore, a
      scFv fragment with specificity for the human C reactive protein was produced in
      B. megaterium. The total yield of the anti-CRP scFv produced in B. megaterium was
      slightly lower compared to E. coli, whereas the specific activity of the purified
      scFvs produced in B. megaterium was higher compared to E. coli. CONCLUSION: B.
      megaterium allows the secretory production of antibody fragments including the
      novel scFab antibody format. The yield and quality of functional antibody
      fragment is comparable to the periplasmic production in E. coli.

PMID- 18042286
TI  - Using protein complexes to predict phenotypic effects of gene mutation.
AB  - BACKGROUND: Predicting the phenotypic effects of mutations is a central goal of
      genetics research; it has important applications in elucidating how genotype
      determines phenotype and in identifying human disease genes. RESULTS: Using a
      wide range of functional genomic data from the yeast Saccharomyces cerevisiae, we
      show that the best predictor of a protein's knockout phenotype is the knockout
      phenotype of other proteins that are present in a protein complex with it. Even
      the addition of multiple datasets does not improve upon the predictions made from
      protein complex membership. Similarly, we find that a proxy for protein complexes
      is a powerful predictor of disease phenotypes in humans. CONCLUSION: We propose
      that identifying human protein complexes containing known disease genes will be
      an efficient method for large-scale disease gene discovery, and that yeast may
      prove to be an informative model system for investigating, and even predicting,
      the genetic basis of both Mendelian and complex disease phenotypes.

PMID- 18042287
TI  - Health inequities: lower socio-economic conditions and higher incidences of
      intestinal parasites.
AB  - BACKGROUND: Intestinal parasitic infections affect child health and development
      and slow down growth, while reducing adults' productivity and work capacity. The
      aim of the present study was to determine and compare the incidences of
      intestinal parasitic infections and the socio-economic status of two near primary
      school children in Manisa, a western city of Turkey. METHODS: A total of 352
      children were involved a questionnaire study from a private school (Ulkem Primary
      School - UPS, 116 children) and a community-based school (Sehzadeler Primary
      School - SPS, 236 children). Of these, stool samples could be obtained from a
      total of 294 students; 97 (83.6%) from UPS, and 197 (83.5%) from SPS. The wet
      mount preparations of the stool samples were examined; samples were also fixed in
      polyvinyl alcohol and examined with modified formalin ethyl acetate sedimentation
      and trichrome staining techniques. Data were analyzed using SPSS for Windows
      version 10.0. The chi-squared test was used for the analytic assessment. RESULTS:
      The percentages of the students found to be infected with intestinal parasites,
      were 78 (39.6%) and 13 (13.4%) in SPS and UPS, respectively. Totally 91 (31.0%)
      of the students from both schools were found to be infected with at least one
      intestinal parasite. Giardia lamblia was found to be the most common pathogenic
      intestinal parasite and Blastocystis hominis was prevalent independently from the
      hygienic conditions. The factors which significantly (p < 0.05) increase the
      incidence of intestinal parasites were uneducated and unemployed mother, lower
      social status of father, living in crowded houses with insufficient indoor
      spaces, using the tap water as drinking water, and living at shanty areas.
      CONCLUSION: Intestinal parasitic infections in school children were found to be a
      public health problem that increased due to lower socio-economic conditions. We
      conclude that organization of education seminars including the topics such as
      prevention of the infectious diseases, improving general hygienic conditions, and
      application of supportive programs for the parents may be suggested not only to
      reduce intestinal parasitic infections, but also to elevate the socio-cultural
      levels.

PMID- 18042288
TI  - Effect of the angiotensin receptor blocker irbesartan on metabolic parameters in
      clinical practice: the DO-IT prospective observational study.
AB  - AIMS: A number of intervention studies have shown that therapy with angiotensin
      receptor blockers, such as irbesartan, can improve metabolic parameters and
      reduce the incidence of diabetes mellitus. It is unknown whether this observation
      also holds true in routine clinical settings. METHODS: We evaluated the effect of
      irbesartan (150 mg or 300 mg/d) together with or without hydrochlorothiazide
      (12.5 mg/d) in 3259 German patients. A total of 750 primary care physicians
      evaluated up to 5 subsequent patients with metabolic syndrome (58.9% diabetic),
      in whom irbesartan therapy was newly initiated (87%) or continued (13%). RESULTS:
      Six months of irbesartan therapy decreased systolic blood pressure by 14% (157.4
      +/- 14.7 vs. 135.0 +/- 10.7 mmHg) and diastolic blood pressure by 13% (92.9 +/-
      9.2 vs. 80.8 +/- 6.8 mmHg). This was associated with a decrease in body weight (
      2.3%), fasting glucose (-9.5%), HbA1c (-4.6%), LDL-cholesterol (-11%),
      triglycerides (-16%) and gamma-GT (-12%) and an increase in HDL-cholesterol
      (+5%). These changes were somewhat more pronounced in male than in female
      patients and in obese than in lean patients. Changes in glucose concentration and
      HbA1c were much more prominent in diabetic patients. CONCLUSION: Irbesartan
      therapy improves metabolic parameters in routine clinical settings. Thus, our
      study confirms previously published results from large intervention trials and
      extends the findings to routine clinical practice.

PMID- 18042289
TI  - Corticomuscular synchronization with small and large dynamic force output.
AB  - BACKGROUND: Over the last few years much research has been devoted to
      investigating the synchronization between cortical motor and muscular activity as
      measured by EEG/MEG-EMG coherence. The main focus so far has been on
      corticomuscular coherence (CMC) during static force condition, for which
      coherence in beta-range has been described. In contrast, we showed in a recent
      study 1 that dynamic force condition is accompanied by gamma-range CMC. The
      modulation of the CMC by various dynamic force amplitudes, however, remained
      uninvestigated. The present study addresses this question. We examined eight
      healthy human subjects. EEG and surface EMG were recorded simultaneously. The
      visuomotor task consisted in isometric compensation for 3 forces (static, small
      and large dynamic) generated by a manipulandum. The CMC, the cortical EEG
      spectral power (SP), the EMG SP and the errors in motor performance (as the
      difference between target and exerted force) were analyzed. RESULTS: For the
      static force condition we found the well-documented, significant beta-range CMC
      (15-30 Hz) over the contralateral sensorimotor cortex. Gamma-band CMC (30-45 Hz)
      occurred in both small and large dynamic force conditions without any significant
      difference between both conditions. Although in some subjects beta-range CMC was
      observed during both dynamic force conditions no significant difference between
      conditions could be detected. With respect to the motor performance, the lowest
      errors were obtained in the static force condition and the highest ones in the
      dynamic condition with large amplitude. However, when we normalized the magnitude
      of the errors to the amplitude of the applied force (relative errors) no
      significant difference between both dynamic conditions was observed. CONCLUSION:
      These findings confirm that during dynamic force output the corticomuscular
      network oscillates at gamma frequencies. Moreover, we show that amplitude
      modulation of dynamic force has no effect on the gamma CMC in the low force range
      investigated. We suggest that gamma CMC is rather associated with the internal
      state of the sensorimotor system as supported by the unchanged relative error
      between both dynamic conditions.

PMID- 18042291
TI  - Acute hepatitis associated with Q fever in a man in Greece: a case report.
AB  - Coxiella burnetii is the causative agent of Q fever. Q fever is a worldwide
      zoonosis that is responsible for various clinical manifestations. However, in
      Greece hepatitis due to Coxiella is rarely encountered. A case of Q fever
      associated with hepatitis is reported here. Diagnosis was made by specific
      serological investigation (enzyme-linked immunosorbent and indirect
      immunofluorescene assays) for Coxiella burnetii.

PMID- 18042290
TI  - A function blocking anti-mouse integrin alpha5beta1 antibody inhibits
      angiogenesis and impedes tumor growth in vivo.
AB  - BACKGROUND: Integrins are important adhesion molecules that regulate tumor and
      endothelial cell survival, proliferation and migration. The integrin alpha5beta1
      has been shown to play a critical role during angiogenesis. An inhibitor of this
      integrin, volociximab (M200), inhibits endothelial cell growth and movement in
      vitro, independent of the growth factor milieu, and inhibits tumor growth in vivo
      in the rabbit VX2 carcinoma model. Although volociximab has already been tested
      in open label, pilot phase II clinical trials in melanoma, pancreatic and renal
      cell cancer, evaluation of the mechanism of action of volociximab has been
      limited because this antibody does not cross-react with murine alpha5beta1,
      precluding its use in standard mouse xenograft models. METHODS: We generated a
      panel of rat-anti-mouse alpha5beta1 antibodies, with the intent of identifying an
      antibody that recapitulated the properties of volociximab. Hybridoma clones were
      screened for analogous function to volociximab, including specificity for
      alpha5beta1 heterodimer and blocking of integrin binding to fibronectin. A subset
      of antibodies that met these criteria were further characterized for their
      capacities to bind to mouse endothelial cells, inhibit cell migration and block
      angiogenesis in vitro. One antibody that encompassed all of these attributes,
      339.1, was selected from this panel and tested in xenograft models. RESULTS: A
      panel of antibodies was characterized for specificity and potency. The affinity
      of antibody 339.1 for mouse integrin alpha5beta1 was determined to be 0.59 nM, as
      measured by BIAcore. This antibody does not significantly cross-react with human
      integrin, however 339.1 inhibits murine endothelial cell migration and tube
      formation and elicits cell death in these cells (EC50 = 5.3 nM). In multiple
      xenograft models, 339.1 inhibited the growth of established tumors by 40-60% (p <
      0.05) and this inhibition correlates with a concomitant decrease in vessel
      density. CONCLUSION: The results herein demonstrate that 339.1, like volociximab,
      exhibits potent anti-alpha5beta1 activity and confirms that inhibition of
      integrin alpha5beta1 impedes angiogenesis and slows tumor growth in vivo.

PMID- 18042292
TI  - Acromioclavicular joint dislocation: a comparative biomechanical study of the
      palmaris-longus tendon graft reconstruction with other augmentative methods in
      cadaveric models.
AB  - BACKGROUND: Acromioclavicular injuries are common in sports medicine. Surgical
      intervention is generally advocated for chronic instability of Rockwood grade III
      and more severe injuries. Various methods of coracoclavicular ligament
      reconstruction and augmentation have been described. The objective of this study
      is to compare the biomechanical properties of a novel palmaris-longus tendon
      reconstruction with those of the native AC+CC ligaments, the modified Weaver-Dunn
      reconstruction, the ACJ capsuloligamentous complex repair, screw and clavicle
      hook plate augmentation. HYPOTHESIS: There is no difference, biomechanically,
      amongst the various reconstruction and augmentative methods. STUDY DESIGN:
      Controlled laboratory cadaveric study. METHODS: 54 cadaveric native
      (acromioclavicular and coracoclavicular) ligaments were tested using the Instron
      machine. Superior loading was performed in the 6 groups: 1) in the intact states,
      2) after modified Weaver-Dunn reconstruction (WD), 3) after modified Weaver-Dunn
      reconstruction with acromioclavicular joint capsuloligamentous repair (WD.ACJ),
      4) after modified Weaver-Dunn reconstruction with clavicular hook plate
      augmentation (WD.CP) or 5) after modified Weaver-Dunn reconstruction with
      coracoclavicular screw augmentation (WD.BS) and 6) after modified Weaver-Dunn
      reconstruction with mersilene tape-palmaris-longus tendon graft reconstruction
      (WD. PLmt). Posterior-anterior (horizontal) loading was similarly performed in
      all groups, except groups 4 and 5. The respective failure loads, stiffnesses,
      displacements at failure and modes of failure were recorded. Data analysis was
      carried out using a one-way ANOVA, with Student's unpaired t-test for unpaired
      data (S-PLUS statistical package 2005). RESULTS: Native ligaments were the
      strongest and stiffest when compared to other modes of reconstruction and
      augmentation except coracoclavicular screw, in both posterior-anterior and
      superior directions (p < 0.005).WD.ACJ provided additional posterior-anterior (P
      = 0. 039) but not superior (p = 0.250) stability when compared to WD
      alone.WD+PLmt, in loads and stiffness at failure superiorly, was similar to WD+CP
      (p = 0.066). WD+PLmt, in loads and stiffness at failure postero-anteriorly, was
      similar to WD+ACJ (p = 0.084).Superiorly, WD+CP had similar strength as WD+BS (p
      = 0.057), but it was less stiff (p < 0.005). CONCLUSIONS AND CLINICAL RELEVANCE:
      Modified Weaver-Dunn procedure must always be supplemented with acromioclavicular
      capsuloligamentous repair to increase posterior-anterior stability. Palmaris
      Longus tendon graft provides both additional superior and posterior-anterior
      stability when used for acromioclavicular capsuloligamentous reconstruction. It
      is a good alternative to clavicle hook plate in acromioclavicular dislocation.

PMID- 18042293
TI  - The association of complex liver disorders with HBV genotypes prevalent in
      Pakistan.
AB  - BACKGROUND: Genotyping of HBV is generally used for determining the
      epidemiological relationship between various virus strains and origin of
      infection mostly in research studies. The utility of genotyping for clinical
      applications is only beginning to gain importance. Whether HBV genotyping will
      constitute part of the clinical evaluation of Hepatitis B patients depends
      largely on the availability of the relevance of the evidence based information.
      Since Pakistan has a HBV genotype distribution which has been considered less
      virulent as investigated by earlier studies from south East Asian countries, a
      study on correlation between HBV genotypes and risk of progression to further
      complex hepatic infection was much needed METHODS: A total of 295 patients with
      HBsAg positive were selected from the Pakistan Medical Research Council's (PMRC)
      out patient clinics. Two hundred and twenty six (77%) were males, sixty nine
      (23%) were females (M to F ratio 3.3:1). RESULTS: Out of 295 patients, 156
      (53.2%) had Acute(CAH), 71 (24.2%) were HBV Carriers, 54 (18.4%) had Chronic
      liver disease (CLD) Hepatitis. 14 (4.7%) were Cirrhosis and HCC patients.
      Genotype D was the most prevalent genotype in all categories of HBV patients,
      Acute (108), Chronic (39), and Carrier (53).Cirrhosis/HCC (7) were HBV/D
      positive. Genotype A was the second most prevalent with 28 (13%) in acute cases,
      12 (22.2%) in chronics, 14 (19.7%) in carriers and 5 (41.7) in Cirrhosis/HCC
      patients. Mixed genotype (A/D) was found in 20 (12.8%) of Acute patients, 3
      (5.6%) of Chronic and 4 (5.6%) of carriers, none in case of severe liver
      conditions. CONCLUSION: Mixed HBV genotypes A, D and A/D combination were present
      in all categories of patients except that no A/D combination was detected in
      severe conditions. Genotype D was the dominant genotype. However, genotype A was
      found to be more strongly associated with severe liver disease. Mixed genotype
      (A/D) did not significantly appear to influence the clinical outcome.

PMID- 18042294
TI  - Fabrication and in vitro deployment of a laser-activated shape memory polymer
      vascular stent.
AB  - BACKGROUND: Vascular stents are small tubular scaffolds used in the treatment of
      arterial stenosis (narrowing of the vessel). Most vascular stents are metallic
      and are deployed either by balloon expansion or by self-expansion. A shape memory
      polymer (SMP) stent may enhance flexibility, compliance, and drug elution
      compared to its current metallic counterparts. The purpose of this study was to
      describe the fabrication of a laser-activated SMP stent and demonstrate
      photothermal expansion of the stent in an in vitro artery model. METHODS: A novel
      SMP stent was fabricated from thermoplastic polyurethane. A solid SMP tube formed
      by dip coating a stainless steel pin was laser-etched to create the mesh pattern
      of the finished stent. The stent was crimped over a fiber-optic cylindrical light
      diffuser coupled to an infrared diode laser. Photothermal actuation of the stent
      was performed in a water-filled mock artery. RESULTS: At a physiological flow
      rate, the stent did not fully expand at the maximum laser power (8.6 W) due to
      convective cooling. However, under zero flow, simulating the technique of
      endovascular flow occlusion, complete laser actuation was achieved in the mock
      artery at a laser power of ~8 W. CONCLUSION: We have shown the design and
      fabrication of an SMP stent and a means of light delivery for photothermal
      actuation. Though further studies are required to optimize the device and assess
      thermal tissue damage, photothermal actuation of the SMP stent was demonstrated.

PMID- 18042295
TI  - The effects of a cyclooxygenase-2 (COX-2) expression and inhibition on human
      uveal melanoma cell proliferation and macrophage nitric oxide production.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) expression has previously been identified in
      uveal melanoma although the biological role of COX-2 in this intraocular
      malignancy has not been elucidated. This study aimed to investigate the effect of
      a COX-2 inhibitor on the proliferation rate of human uveal melanoma cells, as
      well as its effect on the cytotoxic response of macrophages. METHODS: Human uveal
      melanoma cell lines were transfected to constitutively express COX-2 and the
      proliferative rate of these cells using two different methods, with and without
      the addition of Amfenac, was measured. Nitric oxide production by macrophages was
      measured after exposure to melanoma-conditioned medium from both groups of cells
      as well as with and without Amfenac, the active metabolite of Nepafenac. RESULTS:
      Cells transfected to express COX-2 had a higher proliferation rate than those
      that did not. The addition of Amfenac significantly decreased the proliferation
      rate of all cell lines. Nitric oxide production by macrophages was inhibited by
      the addition of melanoma conditioned medium, the addition of Amfenac partially
      overcame this inhibition. CONCLUSION: Amfenac affected both COX-2 transfected and
      non-transfected uveal melanoma cells in terms of their proliferation rates as
      well as their suppressive effects on macrophage cytotoxic activity.

PMID- 18042297
TI  - Vitamin C-induced hyperoxaluria causing reversible tubulointerstitial nephritis
      and chronic renal failure: a case report.
AB  - Vitamin C is a precursor of oxalate and promoter of its absorption, potentially
      causing hyperoxaluria. Malabsorption causes Calcium (Ca) chelation with fatty
      acids, producing enteric hyperoxaluria. CASE: A 73-year-old man with both risk
      factors was hospitalized with serum creatinine of 8.4 mg/dL (versus 1.2 mg/dL
      four months earlier) (normal 0.6-1.3 mg/dL). Given his oxalate-rich diet, chronic
      diarrhea, and daily 680 mg vitamin C and furosemide, we postulated Ca oxalate
      induced nephropathy, a diagnosis confirmed by documenting hyperoxaluria, and
      finding of diffuse intraluminal crystals and extensive interstitial fibrosis on
      biopsy. He was hemodialysed 6 times to remove excess oxalate. Two weeks off
      vitamin C, his creatinine spontaneously fell to 3.1 mg/dL. Three months later, on
      low oxalate diet and 100 mg vitamin B6, urine oxalate to creatinine ratio
      decreased from 0.084 to 0.02 (normal < 0.035), while creatinine fell and stayed
      at 1.8 mg/dL. CONCLUSION: 1) High-dose vitamin C can induce hyperoxaluric
      nephropathy and progressive renal failure, especially if aggravated by diarrhea,
      oxalate-rich diet, metabolic acidosis, and dehydration. 2) The diagnosis should
      be suspected in unexplained renal insufficiency when associated with these risk
      factors. 3) Since prompt treatment could avert end-stage renal disease, we
      recommend monitoring urinary oxalate in patients on high-dose vitamin C and renal
      biopsy if necessary.

PMID- 18042296
TI  - Inhibition of the RAGE products increases survival in experimental models of
      severe sepsis and systemic infection.
AB  - INTRODUCTION: The receptor for advanced glycation end products (RAGE), a multi
      ligand member of the immunoglobulin superfamily, contributes to acute and chronic
      disease processes, including sepsis. METHODS: We studied the possible therapeutic
      role of RAGE inhibition in the cecal ligation and puncture (CLP) model of
      polymicrobial sepsis and a model of systemic listeriosis using mice genetically
      deficient in RAGE expression or mice injected with a rat anti-murine RAGE
      monoclonal antibody. RESULTS: The 7-day survival rates after CLP were 80% for
      RAGE-/- mice (n = 15) (P < 0.01 versus wild-type), 69% for RAGE+/- mice (n = 23),
      and 37% for wild-type mice (n = 27). Survival benefits were evident in BALB/c
      mice given anti-RAGE antibody (n = 15 per group) over serum-treated control
      animals (P < 0.05). Moreover, delayed treatment with anti-RAGE antibody up to 24
      hours after CLP resulted in a significant survival benefit compared with control
      mice. There was no significant increase in tissue colony counts from enteric Gram
      negative or Gram-positive bacteria in animals treated with anti-RAGE antibody.
      RAGE-/-, RAGE+/-, and anti-RAGE antibody-treated animals were resistant to
      lethality from Listeria monocytogenes by almost two orders of magnitude compared
      with wild-type mice. CONCLUSION: Further studies are warranted to determine the
      clinical utility of anti-RAGE antibody as a novel treatment for sepsis.

PMID- 18042298
TI  - Using participatory design to develop (public) health decision support systems
      through GIS.
AB  - BACKGROUND: Organizations that collect substantial data for decision-making
      purposes are often characterized as being 'data rich' but 'information poor'.
      Maps and mapping tools can be very useful for research transfer in converting
      locally collected data into information. Challenges involved in incorporating GIS
      applications into the decision-making process within the non-profit (public)
      health sector include a lack of financial resources for software acquisition and
      training for non-specialists to use such tools. This on-going project has two
      primary phases. This paper critically reflects on Phase 1: the participatory
      design (PD) process of developing a collaborative web-based GIS tool. METHODS: A
      case study design is being used whereby the case is defined as the data analyst
      and manager dyad (a two person team) in selected Ontario Early Year Centres
      (OEYCs). Multiple cases are used to support the reliability of findings. With
      nine producer/user pair participants, the goal in Phase 1 was to identify
      barriers to map production, and through the participatory design process, develop
      a web-based GIS tool suited for data analysts and their managers. This study has
      been guided by the Ottawa Model of Research Use (OMRU) conceptual framework.
      RESULTS: Due to wide variations in OEYC structures, only some data analysts used
      mapping software and there was no consistency or standardization in the software
      being used. Consequently, very little sharing of maps and data occurred among
      data analysts. Using PD, this project developed a web-based mapping tool (EYEMAP)
      that was easy to use, protected proprietary data, and permit limited and
      controlled sharing between participants. By providing data analysts with training
      on its use, the project also ensured that data analysts would not break
      cartographic conventions (e.g. using a chloropleth map for count data).
      Interoperability was built into the web-based solution; that is, EYEMAP can read
      many different standard mapping file formats (e.g. ESRI, MapInfo, CSV).
      DISCUSSION: Based on the evaluation of Phase 1, the PD process has served both as
      a facilitator and a barrier. In terms of successes, the PD process identified two
      key components that are important to users: increased data/map sharing
      functionality and interoperability. Some of the challenges affected developers
      and users; both individually and as a collective. From a development perspective,
      this project experienced difficulties in obtaining personnel skilled in web
      application development and GIS. For users, some data sharing barriers are beyond
      what a technological tool can address (e.g. third party data). Lastly, the PD
      process occurs in real time; both a strength and a limitation. Programmatic
      changes at the provincial level and staff turnover at the organizational level
      made it difficult to maintain buy-in as participants changed over time. The
      impacts of these successes and challenges will be evaluated more concretely at
      the end of Phase 2. CONCLUSION: PD approaches, by their very nature, encourage
      buy-in to the development process, better addresses user-needs, and creates a
      sense of user-investment and ownership.

PMID- 18042299
TI  - Recombination rate and protein evolution in yeast.
AB  - BACKGROUND: Theory and artificial selection experiments show that recombination
      can promote adaptation by enhancing the efficacy of natural selection, but the
      extent to which recombination affects levels of adaptation across the genome is
      still an open question. Because patterns of molecular evolution reflect long-term
      processes of mutation and selection in nature, interactions between recombination
      rate and genetic differentiation between species can be used to test the benefits
      of recombination. However, this approach faces a major difficulty: different
      evolutionary processes (i.e. negative versus positive selection) produce opposing
      relationships between recombination rate and genetic divergence, and obscure
      patterns predicted by individual benefits of recombination. RESULTS: We use a
      combination of polymorphism and genomic data from the yeast Saccharomyces
      cerevisiae to infer the relative importance of nearly-neutral (i.e. slightly
      deleterious) evolution in different gene categories. For genes with high
      opportunities for slightly deleterious substitution, recombination substantially
      reduces the rate of molecular evolution, whereas divergence in genes with little
      opportunity for slightly deleterious substitution is not strongly affected by
      recombination. CONCLUSION: These patterns indicate that adaptation throughout the
      genome can be strongly influenced by each gene's recombinational environment, and
      suggest substantial long-term fitness benefits of enhanced purifying selection
      associated with sexual recombination.

PMID- 18042300
TI  - The Warwick-Edinburgh Mental Well-being Scale (WEMWBS): development and UK
      validation.
AB  - BACKGROUND: There is increasing international interest in the concept of mental
      well-being and its contribution to all aspects of human life. Demand for
      instruments to monitor mental well-being at a population level and evaluate
      mental health promotion initiatives is growing. This article describes the
      development and validation of a new scale, comprised only of positively worded
      items relating to different aspects of positive mental health: the Warwick
      Edinburgh Mental Well-Being Scale (WEMWBS). METHODS: WEMWBS was developed by an
      expert panel drawing on current academic literature, qualitative research with
      focus groups, and psychometric testing of an existing scale. It was validated on
      a student and representative population sample. Content validity was assessed by
      reviewing the frequency of complete responses and the distribution of responses
      to each item. Confirmatory factor analysis was used to test the hypothesis that
      the scale measured a single construct. Internal consistency was assessed using
      Cronbach's alpha. Criterion validity was explored in terms of correlations
      between WEMWBS and other scales and by testing whether the scale discriminated
      between population groups in line with pre-specified hypotheses. Test-retest
      reliability was assessed at one week using intra-class correlation coefficients.
      Susceptibility to bias was measured using the Balanced Inventory of Desired
      Responding. RESULTS: WEMWBS showed good content validity. Confirmatory factor
      analysis supported the single factor hypothesis. A Cronbach's alpha score of 0.89
      (student sample) and 0.91 (population sample) suggests some item redundancy in
      the scale. WEMWBS showed high correlations with other mental health and well
      being scales and lower correlations with scales measuring overall health. Its
      distribution was near normal and the scale did not show ceiling effects in a
      population sample. It discriminated between population groups in a way that is
      largely consistent with the results of other population surveys. Test-retest
      reliability at one week was high (0.83). Social desirability bias was lower or
      similar to that of other comparable scales. CONCLUSION: WEMWBS is a measure of
      mental well-being focusing entirely on positive aspects of mental health. As a
      short and psychometrically robust scale, with no ceiling effects in a population
      sample, it offers promise as a tool for monitoring mental well-being at a
      population level. Whilst WEMWBS should appeal to those evaluating mental health
      promotion initiatives, it is important that the scale's sensitivity to change is
      established before it is recommended in this context.

PMID- 18042301
TI  - Recommended level of physical activity and health-related quality of life among
      Japanese adults.
AB  - BACKGROUND: The benefits of a recommended level of physical activity on
      physiological health indicators such as morbidity and mortality are well
      accepted, but less research has addressed whether or not the association between
      the recommended level of physical activity and a health-related quality of life
      (HRQOL) exists in the Japanese population. Thus, the present study examined
      whether the recommended physical activity would be associated with HRQOL in the
      general Japanese middle-aged population. METHODS: Data were obtained from 1211
      male and female respondents (39.4 +/- 10.9 year, mean +/- SD) from an Internet
      based survey of registrants of an Internet research service. Physical activity
      level was estimated from the short form of the International Physical Activity
      Questionnaire. HRQOL was assessed with the Medical Outcomes Survey Short Form-8
      questionnaire (SF-8). Based on the current national guidelines for exercise in
      Japan, respondents were divided into a recommended group, an insufficient group,
      and an inactive group according to their estimated weekly physical activity
      level. Multivariate analyses of covariance were utilized. RESULTS: Across both
      genders, the recommended group had significantly higher physical functioning (PF)
      scores than the inactive group (p < .05). Additionally, across both genders, the
      recommended group had significantly higher general health perception scores than
      the insufficient and inactive groups (p < .05). The recommended group had
      significantly higher vitality scores than the insufficient and inactive groups in
      males, and higher than only the inactive group in females (p < .05). The
      insufficient group had significantly higher PF scores than the inactive group
      across both genders (p < .05). The recommended group had significantly higher
      physical component scores than the inactive group (p = .001). CONCLUSION:
      Individuals who attained the recommended level of physical activity had better
      scores on some dimensions of HRQOL than those who did not, suggesting that the
      recommended level of physical activity may be applicable not only to the
      physiological objective outcomes but also to some dimensions in both the physical
      and mental aspects of HRQOL.

PMID- 18042302
TI  - The effect of priority setting decisions for new cancer drugs on medical
      oncologists' practice in Ontario: a qualitative study.
AB  - BACKGROUND: Health care policies, including drug-funding policies, influence
      physician practice. Funding policies are especially important in the area of
      cancer care since cancer is a leading cause of death that is responsible for a
      significant level of health care expenditures. Recognizing the rising cost of
      cancer therapies, Cancer Care Ontario (CCO) established a funding process to
      provide access to new, effective agents through a "New Drug Funding Program"
      (NDFP). The purpose of this study is to describe oncologists' perceptions of the
      impact of NDFP priority setting decisions on their practice. METHODS: This is a
      qualitative study involving semi-structured, in-depth interviews with 46 medical
      oncologists in Ontario. Oncologists were asked to describe the impact of CCO's
      NDFP drug funding decisions on their practice. Analysis of interview transcripts
      commenced with data collection. RESULTS: Our key finding is that many of the
      medical oncologists who participated in this study did not accept limits when
      policy decisions limit access to cancer drugs they feel would benefit their
      patients. Moreover, overcoming those limits had a significant impact on
      oncologists' practice in terms of how they spend their time and energy and their
      relationship with patients. CONCLUSION: When priority setting decisions limit
      access to cancer medications, many oncologists' efforts to overcome those limits
      have a significant impact on their practice. Policy makers need to seriously
      consider the implications of their decisions on physicians, who may go to
      considerable effort to circumvent their policies in the name of patient advocacy.

PMID- 18042303
TI  - Characterization of Smoc-1 uncovers two transcript variants showing differential
      tissue and age specific expression in Bubalus bubalis.
AB  - BACKGROUND: Secreted modular calcium binding protein-1 (Smoc-1) belongs to the BM
      40 family which has been implicated with tissue remodeling, angiogenesis and bone
      mineralization. Besides its anticipated role in embryogenesis, Smoc-1 has been
      characterized only in a few mammalian species. We made use of the consensus
      sequence (5' CACCTCTCCACCTGCC 3') of 33.15 repeat loci to explore the buffalo
      transcriptome and uncovered the Smoc-1 transcript tagged with this repeat. The
      main objective of this study was to gain an insight into its structural and
      functional organization, and expressional status of Smoc-1 in water buffalo,
      Bubalus bubalis. RESULTS: We cloned and characterized the buffalo Smoc-1,
      including its copy number status, in-vitro protein expression, tissue & age
      specific transcription/translation, chromosomal mapping and localization to the
      basement membrane zone. Buffalo Smoc-1 was found to encode a secreted
      matricellular glycoprotein containing two EF-hand calcium binding motifs
      homologous to that of BM-40/SPARC family. In buffalo, this single copy gene
      consisted of 12 exons and was mapped onto the acrocentric chromosome 11. Though
      this gene was found to be evolutionarily conserved, the buffalo Smoc-1 showed
      conspicuous nucleotide/amino acid changes altering its secondary structure
      compared to that in other mammals. In silico analysis of the Smoc-1 proposed its
      glycoprotein nature with a calcium dependent conformation. Further, we unveiled
      two transcript variants of this gene, varying in their 3'UTR lengths but both
      coding for identical protein(s). Smoc-1 evinced highest expression of both the
      variants in liver and modest to negligible in other tissues. The relative
      expression of variant-02 was markedly higher compared to that of variant-01 in
      all the tissues examined. Moreover, expression of Smoc-1, though modest during
      the early ages, was conspicuously enhanced after 1 year and remained consistently
      higher during the entire life span of buffalo with gradual increment in
      expression of variant-02. Immunohistochemically, Smoc-1 was localized in the
      basement membrane zones and extracellular matrices of various tissues.
      CONCLUSION: These data added to our understandings about the tissue, age and
      species specific functions of the Smoc-1. It also enabled us to demonstrate
      varying expression of the two transcript variants of Smoc-1 amongst different
      somatic tissues/gonads and ages, in spite of their identical coding frames.
      Pursuance of these variants for their roles in various disease phenotypes such as
      hepatocellular carcinoma and angiogenesis is envisaged to establish broader
      biological significance of this gene.

PMID- 18042304
TI  - Prospective memory or prospective attention: physiological and pharmacological
      support for an attentional model.
AB  - Previous studies have reported that nicotine, a cholinergic agonist, could
      improve prospective memory (PM) - memory for a delayed intention - in healthy
      young adults. In the present study, we asked whether nicotine effects on PM
      performance were attributable to a drug-induced non-specific increase in arousal.
      Therefore, a double-blind, placebo-controlled study compared the effect of
      nicotine to the effect of an arousal manipulation on PM performance. All
      participants were non-smokers; half received 1 mg nicotine via a nasal spray and
      half received a matched placebo. Within these groups, half of the volunteers were
      exposed to hard anagrams and exhibited heightened tense arousal, while half of
      the volunteers were given easy anagrams and showed no change in arousal. These
      manipulations resulted in four conditions, placebo/low-arousal (n=12),
      placebo/high-arousal (n=10), nicotine/low-arousal (n=12), nicotine/high-arousal
      (n=13). All participants completed an ongoing lexical decision task while
      maintaining a PM intention (to make a separate, non-focal, response to certain
      items embedded within the ongoing task). When introduced separately, both
      nicotine and high tense arousal improved PM performance, but when combined, this
      improvement was eliminated. It is argued that both nicotine and high tense
      arousal increase attentional resources, specifically improving monitoring of the
      PM targets, but when combined they no longer produce beneficial effects.
      Additionally, given that nicotine exerted no effect on physiological or
      subjective measures of arousal, we conclude that the observed effects of nicotine
      and of arousal on PM performance are driven by different pharmacological
      mechanisms.

PMID- 18042305
TI  - Urine pH is an indicator of dietary acid-base load, fruit and vegetables and meat
      intakes: results from the European Prospective Investigation into Cancer and
      Nutrition (EPIC)-Norfolk population study.
AB  - Evidence exists that a more acidic diet is detrimental to bone health. Although
      more precise methods exist for measurement of acid-base balance, urine pH
      reflects acid-base balance and is readily measurable but has not been related to
      habitual dietary intake in general populations. The present study investigated
      the relationship between urine pH and dietary acid-base load (potential renal
      acid load; PRAL) and its contributory food groups (fruit and vegetables, meats,
      cereal and dairy foods). There were 22,034 men and women aged 39-78 years living
      in Norfolk (UK) with casual urine samples and dietary intakes from the European
      Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk FFQ. A sub
      study (n 363) compared pH in casual samples and 24 h urine and intakes from a 7 d
      diary and the FFQ. A more alkaline diet (low PRAL), high fruit and vegetable
      intake and lower consumption of meat was significantly associated with a more
      alkaline urine pH before and after adjustment for age, BMI, physical activity and
      smoking habit and also after excluding for urinary protein, glucose, ketones,
      diagnosed high blood pressure and diuretic medication. In the sub-study the
      strongest relationship was found between the 24 h urine and the 7 d diary. In
      conclusion, a more alkaline diet, higher fruit and vegetable and lower meat
      intake were related to more alkaline urine with a magnitude similar to
      intervention studies. As urine pH relates to dietary acid-base load its use to
      monitor change in consumption of fruit and vegetables, in individuals, warrants
      further investigation.

PMID- 18042306
TI  - Weight-loss maintenance 1, 2 and 5 years after successful completion of a weight
      loss programme.
AB  - The objective was to assess weight-loss maintenance in individuals who
      successfully completed a commercial weight-loss programme at multiple sites in
      the United States. A total of 699 lifetime members of Weight Watchers represented
      the national sample and 217 additional lifetime members served as an oversample.
      Lifetime members were asked to self-report their current weight 1, 2, and 5 years
      after they had successfully completed the programme. Additional lifetime members
      served as an oversample whose weights were measured. The discrepancy between
      reported and measured weight in the oversample was used to adjust the self
      reported weights of the national sample. Seventy-one percent of participants were
      middle-aged or older and 95.3 % were female; their mean starting BMI was 27.6 (sd
      3.6) kg/m2. The percentage of Weight Watchers lifetime members who maintained at
      least 5 % of their weight loss 1, 2 and 5 years after successful completion of
      the programme was 79.8, 71.0, and 50.0, respectively. The percentage of
      participants who remained below their goal weight 1, 2 and 5 years after
      completion of the programme was 26.5, 20.5, and 16.2, respectively. Results
      obtained with this group of successful Weight Watchers members are not directly
      comparable to those obtained with clinical samples of obese dieters because the
      current sample comprises only the most successful Weight Watchers participants.
      However, these results provide further evidence that maintenance of weight loss
      in those who successfully lose weight in one commercial weight-loss programme is
      more feasible than data from clinical populations have suggested.

PMID- 18042307
TI  - The development and evaluation of a novel computer program to assess previous-day
      dietary and physical activity behaviours in school children: the Synchronised
      Nutrition and Activity Program (SNAP).
AB  - Self-report recall questionnaires used to measure physical activity and dietary
      intake in children can be labour intensive and monotonous and tend to focus on
      either dietary intake or physical activity. The web-based software, Synchronised
      Nutrition and Activity Program (SNAP), was developed to produce a novel, simple,
      quick and engaging method of assessing energy balance-related behaviours at a
      population level, combining principles from new and existing 24 h recall
      methodologies, set within a user-friendly interface. Dietary intake was measured
      using counts for twenty-one food groups and physical activity levels were
      measured in min of moderate to vigorous physical activity (MVPA). A combination
      of the mean difference between methods, type II regression and non-parametric
      limits of agreement techniques were used to examine the accuracy and precision of
      SNAP. Method comparison analyses demonstrated a good agreement for both dietary
      intake and physical activity behaviours. For dietary variables, accuracy of SNAP
      (mean difference) was within +/- 1 count for the majority of food groups. The
      proportion of the sample with between-method agreement within +/- 1 count ranged
      from 0.40 to 0.99. For min of MVPA, there was no substantial fixed or
      proportional bias, and a mean difference between methods (SNAP - accelerometry)
      of -9 min. SNAP provides a quick, accurate, low-burden, cost-effective and
      engaging method of assessing energy balance behaviours at a population level.
      Tools such as SNAP, which exploit the popularity, privacy and engagement of the
      computer interface, and linkages with other datasets, could make a substantial
      contribution to future public health monitoring and research.

PMID- 18042308
TI  - Addition of oat hulls to an extruded rice-based diet for weaner pigs ameliorates
      the incidence of diarrhoea and reduces indices of protein fermentation in the
      gastrointestinal tract.
AB  - An experiment was conducted to determine whether adding oat hulls to weaner pig
      diets based on extruded rice or unprocessed wheat influenced post-weaning
      diarrhoea (PWD) and protein fermentation in the large intestine. Ninety-six male
      piglets (5.16 (SEM 0.08) kg) were allocated to (i) extruded rice plus animal
      proteins (RAP); (ii) RAP with added oat hulls (20 g/kg); (iii) wheat plus animal
      proteins (WAP); (iv) WAP with added oat hulls (20 g/kg). Blood and faecal samples
      were collected on days 7 and 14 after weaning at about age 21 d. Pigs fed RAP had
      more PWD than pigs fed WAP (P < 0.05). Oat hull supplementation to diet RAP
      decreased the incidence of PWD (P < 0.05). The total-tract digestibility of DM,
      starch and energy was higher in rice-based diets than in wheat-based diets (P <
      0.001); however, oat hulls decreased digestibility of DM and gross energy (P <
      0.001). Pigs fed RAP had higher plasma creatinine concentrations (P < 0.01),
      which were positively correlated to cumulative beta-haemolytic Escherichia coli
      scores after weaning (R2 0.928; P = 0.015). Addition of oat hulls decreased
      plasma urea concentrations only in pigs fed RAP (interaction; P < 0.05). Pigs fed
      RAP had lower faecal total biogenic amine concentrations than pigs fed WAP (P <
      0.001). Oat hull supplementation tended to decrease total biogenic amine
      concentrations (P = 0.103). These data indirectly suggest that a mostly insoluble
      dietary fibre source such as oat hulls can decrease PWD in dietary situations
      where there may be a misbalance of carbohydrate to protein entering the hindgut.

PMID- 18042309
TI  - The mucosal cellular response to infection with Ancylostoma ceylanicum.
AB  - Although hookworms are known to stimulate inflammatory responses in the
      intestinal mucosa of their hosts, there is little quantitative data on this
      aspect of infection. Here we report the results of experiments conducted in
      hamsters infected with Ancylostoma ceylanicum. Infection resulted in a marked
      increase in goblet cells in the intestinal mucosa, which was dependent on the
      number of adult worms present and was sustained as long as worms persisted (over
      63 days) but returned to baseline levels within 7 days of the removal of worms by
      treatment with ivermectin. Increased mast cell responses were also recorded.
      Levels were again dependent on the intensity of worm burdens and lasted as long
      as 63 days after infection. When worms were eliminated, mast cell numbers took
      over 2 weeks to return to normal. Paneth cell numbers fell soon after infection,
      the degree of reduction being dependent on the worm burden. After clearance of
      worms, Paneth cell numbers returned to normal within a week, but then rebounded
      and numbers rose to higher levels than those in control naive animals. The time
      course of the response was similar whether animals experienced a chronic low
      intensity infection without loss of worms or a higher intensity infection during
      the course of which worm burdens were gradually reduced. Clearly, A. ceylanicum
      was able to induce a marked inflammatory response in its host's intestine which
      was sustained for over 9 weeks after infection, and which hamsters appeared able
      to tolerate well. Our data draw attention to the resilience of hookworms which,
      unlike many other nematodes, are able to survive for many weeks in a highly
      inflamed intestinal tract.

PMID- 18042310
TI  - The relativity of bad decisions: social comparison as a means to alleviate
      regret.
AB  - In two studies, we examined the role of social comparisons in regret management.
      In the first study, participants received a (relatively) negative outcome after
      which they were presented with base-rate information about the performance of
      other participants in the experiment. Results showed that experienced regret
      decreased as a result of base-rate information showing that most others made even
      worse decisions than oneself. In the second study, we investigated whether people
      actively seek this kind of consensual information to validate their decision.
      After inducing regret by means of a manipulated outcome in a trivia quiz,
      participants could obtain information about the outcomes of previous participants
      or about the type of items used in the quiz. Participants' preference was
      determined by whether or not they believed that they would be given a second
      chance. In case of a negative and final outcome, participants preferred
      information about the prevalence of others who had an even worse outcome. When
      the outcome was non-final, participants preferred information about the type of
      items used in the test. Both strategies were accompanied with a decrease in
      regret. Implications for research on regret and decision making are discussed.

PMID- 18042311
TI  - Once-monthly oral ibandronate compared with weekly oral alendronate in
      postmenopausal osteoporosis: results from the head-to-head MOTION study.
AB  - OBJECTIVE: Oral ibandronate 150 mg is the first bisphosphonate approved for once
      monthly treatment of postmenopausal osteoporosis. To investigate whether once
      monthly ibandronate 150 mg increases lumbar spine and total hip bone mineral
      density (BMD) to the same degree as weekly alendronate 70 mg. RESEARCH DESIGN AND
      METHODS: This was a 12-month, randomised, multinational, multicentre, double
      blind, double-dummy, parallel-group, non-inferiority trial, conducted in 65
      centres in North America, Latin America, Europe and South Africa. The study
      included postmenopausal women, mean lumbar spine (L2-L4) BMD T-score < -2.5 and >
      or = -5.0. Patients received either ibandronate 150 mg once monthly or
      alendronate 70 mg once weekly. MAIN OUTCOME MEASURES: Co-primary efficacy
      endpoints were 12-month change (%) from baseline in mean lumbar spine and total
      hip BMD. Changes (%) from baseline in trochanter and femoral neck BMD were also
      evaluated. Adverse events were monitored throughout. Once-monthly ibandronate was
      considered non-inferior to weekly alendronate if the lower boundary of the one
      sided 97.5% confidence interval (CI) (or two-sided 95% CI) was > or = -1.41% for
      lumbar spine and > or = -0.87% for total hip. RESULTS: Mean relative 12-month
      changes were 5.1% and 5.8% (95% CI for difference, -1.13, -0.23) in lumbar spine
      and 2.9% and 3.0% (95% CI for difference, -0.38, 0.18) in total hip BMD with once
      monthly ibandronate and weekly alendronate, respectively; meeting the non
      inferiority criteria at both sites. Gains in trochanter and femoral neck BMD were
      similar with both treatments. Both regimens were well tolerated. TRIAL
      REGISTRATION: The MOTION study is registered with the International Federation of
      Pharmaceutical Manufacturers and Associations trial portal, under the ID number
      MM17385. CONCLUSIONS: Once-monthly ibandronate was shown to be clinically
      comparable to weekly alendronate at increasing BMD after 12 months in both the
      lumbar spine and total hip.

PMID- 18042312
TI  - [Multiplex minisequencing applied in detection of human functional CYP21 gene
      mutations].
AB  - We analyzed seven most common mutations within the CYP21B gene, responsible for
      congenital adrenal hyperplasia (CAH), using the minisequencing method. Functional
      CYP21B gene sequences were amplified with the pair of specific primers that
      pevented amplification of pseudogene CYP21P or pseudogene CYP21P/active CYP21
      hybrids. Multiplex minisequencing (SNaPShot PCR) assay was performed with
      fluorescent dideoxynucleotides ([F]ddNTPs) and originally designed primers,
      claiming seven most common mutation sites responsible for the CAH symptoms. Using
      the method we detected five novel substitutions of unknown effect on the CAH
      course in five out of seven analyzed mutation sites. Compared to classic SNPs
      analyzing methods, especially single SNP detection, multiplex minisequencing is
      the same highly specific and sensitive but much faster one. The method is
      recommended for any population screened for known mutations.

PMID- 18042313
TI  - [Insulin glargine improves fasting blood glucose levels in prepubertal children
      with unsatisfactorily controlled type 1 diabetes].
AB  - The aim of this prospective cross-over study was to compare glycemic control on
      NPH insulin (NPH) and on glargine in unsatisfactorily controlled type 1 diabetic
      prepubertal children. MATERIAL AND METHODS: 14 patients, aged 6-12 years, on
      multiple insulin injections regimen were included. The study protocol: (i) a 6
      month therapy with NPH as basal insulin and (ii) a 6-month therapy with glargine
      as basal insulin, in a random order. RESULTS: After 4 and 6 months mean blood
      glucose levels were similar on glargine and on NPH. After 6 months on NPH fasting
      blood glucose levels were similar to baseline (9.3+/-1.5 and 9.8+/-1.6 mmol/l
      respectively), while on glargine they were significantly lower compared to
      baseline (8.0+/-1.4 vs. 9.8+/-1.6 mmol/l, p=0.04) and markedly lower than after 6
      months on NPH (8.0+/-1.4 vs. 9.3+/-1.5 mmol/l, p=0.077). HbA1c was lower on
      glargine compared to NPH, but only after 4 months the difference was
      statistically significant (7.1+/-0.16 vs. 7.74+/-0.25%, p=0.007). No severe
      hypoglycemia or ketoacidosis occurred. CONCLUSION: In preadolescent children with
      unsatisfactorily controlled type 1 diabetes glargine constitutes a useful and
      safe alternative to NPH, providing better early morning and good total glycemic
      control, not increasing the risk of severe hypoglycemia; taking it into account
      the health care systems should participate in its costs for those who can not
      afford or tolerate an insulin pump.

PMID- 18042314
TI  - [Leptin concentration and insulin sensitivity in type 1 diabetic children and
      adolescents].
AB  - THE AIM OF THE STUDY: was to estimate the relationship between serum leptin
      levels and insulin sensitivity and components of metabolic syndrome in type 1
      diabetic children and adolescents. MATERIALS AND METHODS: 158 patients with type
      1 diabetes mellitus (70 girls and 88 boys) aged from 8.2 to 18.4 years (mean:
      14.1+/-3.1 years) were included into the study. The diabetes duration ranged from
      1.6 to 14.7 years (mean: 3.8+/-2.5 years). The height, weight, waist
      circumference (WC), skin folds and blood pressure were measured. Body mass index
      (BMI-SDS), body fat (BF) according to Slaughter formula, and daily dose of
      insulin were calculated. HbA1c (HPLC method) and serum lipids (enzymatic method)
      concentrations were examined. Serum leptin concentration was measured by ELISA
      method. Euglycemic-hyperinsulinemic clamp was performed to estimate insulin
      resistance. Glucose disposal rate (M index) determined during the last 30 min of
      the test was calculated as a surrogate of insulin resistance. RESULTS: Serum
      leptin levels ranged from 1.47 to 57.39 ng/ml (median [quartiles]: 4.60 [3.18
      10.2]). M index was 2.10-15.19 mg/kg/min. (median [quartiles]: 7.04 [5.57-8.69].
      Leptin was positively correlated with BMI-SDS, WC, skin folds and BF. During
      puberty leptin levels increased in girls, but in boys the highest levels were
      observed at Tanner stage 3. Leptin concentrations, normalized for BMI-SDS or BF,
      were significantly higher in females than in males at Tanner stages 4 (pc=0.047)
      and 5 (pc<0.001). Leptin was negatively correlated with M index (r=-0.26; p=0.001
      adjusted for sex and puberty), but after adjusting for BF or BMI-SDS there were
      no significant correlations. Leptin was not significantly associated with HDL
      cholesterol, SBP and DBP. Using the multivariate linear regression models, we
      found that plasma leptin remained significantly associated with TG. CONCLUSION:
      It is likely that the observed relationship between leptin concentration and
      insulin resistance in young patients with type 1 diabetes is due to body fat
      composition rather than represents an independent association in this group.

PMID- 18042315
TI  - [Health school readiness of short-statured rural and urban children against of
      peers' background].
AB  - THE AIM OF THIS WORK: is to estimate the frequency of short-stature phenomena,s
      among 6-7 y.o. rural and urban children and to assess the physical fitness and
      body posture of short-statured girls and boys against of peers, background.
      MATERIAL AND METHODS: The researches were conducted on 436 children: 232 boys and
      204 girls from village and city. The used methods were: anthropometric
      measurements (body height), simple physical fitness tests, the examination of
      body posture, poll technique and basic statistical methods. RESULTS: The analysis
      show that there are differences in the frequency of short-stature phenomena,s
      between girls and boys and between rural and urban children. Taking into
      consideration developmental age, the level of physical fitness of short-statured
      children is in "narrow norm" (between 25% and 75% of population) most often. Body
      posture of short-statured 6-7 y.o. children is characterized by typical features
      in this ontogenesis period: crooked knees, flat-crooked feet, protruding shoulder
      blades, emphasized stomach, asymmetrical shoulders and shoulder blades,
      staggering. CONCLUSIONS: There is a need of systematical monitoring of the
      biological development of short-statured children, particularly taking into
      consideration girls and boys whose physical fitness level is weak and body
      posture is incorrect, and also that kind of children, who grow in families with a
      low social-economic and educational status.

PMID- 18042316
TI  - [Functional and dynamic asymmetry of simple reaction time in female fencers].
AB  - THE AIM OF THE STUDY: was to assess the functional and dynamic components of
      asymmetry in the simple reaction time in female fencers, holders of the master,
      first or second sport class. MATERIAL AND METHODS: A group of 45 female fencers,
      classified into 3 groups according to the sport class were studied. Dynamic
      asymmetry was assessed with the use of the Viennese Test System. The time of
      reaction and of simple movement to visual and acoustic stimuli was determined.
      RESULTS: Master class fencers exhibited a high (40%) left-side domination while
      those from the other two groups had right-side asymmetry (80%), the difference in
      the median reaction time between those groups being significant (p<0.05).
      CONCLUSIONS: The pronounced dynamic asymmetry observed in master class fencers
      was due to a highly specific, one-sided training. It should be emphasised that
      asymmetrical exercises combined with very high training loads applied in the
      contemporary sport may lead to overloads of extremities, spine deformations and
      injuries.

PMID- 18042317
TI  - [Dental and skeletal age in children with growth hormone deficiency treated with
      growth hormone--preliminary report].
AB  - INTRODUCTION: Somatotrophic hypofunction (growth hormone deficiency--GHD) is one
      of the basic indications for treatment with growth hormone. One of
      characteristics of this disease is a delay of bone age in comparison to calendar
      one. AIM OF THE STUDY: The authors refer to the difference between chronological
      age and dental and skeletal age in children with growth hormone deficiency
      depending on the duration of treatment with growth hormone. MATERIALS AND METHOD:
      Twenty five patients with somatotrophic pituitary gland deficiency treated with
      growth hormone constituted research material. The patients were divided into two
      groups depending on substitution therapy period length. Group I consisted of 6
      children with a treatment time shorter than 1 year, while group II--19
      individuals--included children with a therapy duration of over 1 year. All
      children were subject to clinical orthodontic examination--the kind of dental
      occlusion defect was evaluated--and radiological diagnostics was conducted-
      orthopantomogram and cephalogram. Matiegka and Lukasova clinical method was used
      for evaluation of dental age, while for radiological dental age evaluation the
      Demirjian's method. Radiological evaluation, conducted basing on X-rays of palm
      and wrist and radiological atlas of Greulich-Pyle, was used for determination of
      skeletal age. Schwarz and Steiner's analyses were used for cephalogram
      evaluation, considering the following angle parameters: SNA, SNB, ANB and G
      mandible angle. RESULTS: In group I malocclusions represented 66,6%, where of
      most common were class II malocclusion--33.3%, then increased overbite and open
      bites 16.7% of cases. In this group in all subjects dental abnormalities were
      diagnosed. In the group of children treated with growth hormone longer than 1
      year (group II) malocclusion represented 86.6%, class II malocclusion 46.7%,
      scissor-bite and increased overbite 13.3%, furthermore in 66.7% open bite and
      class III malocclusion were diagnosed. In 33.3% teeth discrepancies were found.
      In both examined groups dominated skeletal class II . Furthermore in both
      examined groups an increase of G angle on about 0.3% was stated. CONCLUSIONS: A
      longer substitution therapy period, and thus generally longer hormone influence
      period, intensifies its influence on craniofacial complex. This influence is
      advantageous and leads to a decrease of the disproportion in jaw dimensions, thus
      preventing the occurrence of gnathic and malocclusion.

PMID- 18042318
TI  - [Metabolic control and insulin administration in a girl with Turner syndrome and
      type 1 diabetes during long-term growth hormone therapy].
AB  - Many surveys have indicated that short stature affects at least 95% of all
      patients with Turner syndrome (TS). It is also clear that growth hormone (GH)
      therapy can accelerate the physical development in girls with TS. According to
      some clinical experience diabetes type 1 may be considered as a contraindication
      for GH therapy leading to low efficacy and high risk of late complications due to
      hyperglycaemia and elevated IGF-1 level. We present the results of growth hormone
      therapy on the metabolic control in a girl with TS and type 1 diabetes treated
      with continuous subcutaneous insulin infusion. The parameters of metabolic
      control and insulin doses were compared before and after introducing GH therapy.
      The correct diurnal glycemia profile was obtained after 4-fold increase of basal
      insulin and 2-fold increase of the total daily dose. The acceleration of growth
      was observed during 3.5-year therapy and average linear growth velocity was 7
      cm/year. Growth hormone administration in children with Turner syndrome and type
      1 diabetes can be efficacious and safe.

PMID- 18042319
TI  - Delay of cystectomy: for whom does it really matter?

PMID- 18042320
TI  - Management of a patient with a mass in an ectopic kidney.

PMID- 18042321
TI  - Overactive bladder syndrome presentations at the 31st International
      Urogynecological Association Annual Meeting.
AB  - There were 586 abstracts presented at the 31st Annual Meeting of the
      International Urogynecological Association in Athens, Greece, in September 2006.
      Many of these abstracts focused on the common condition of overactive bladder
      syndrome. The results of large multicenter industry-sponsored trials such as
      MATRIX, STAR, and SUNRISE were presented. Smaller trials of new treatments,
      including pudendal nerve stimulation and botulinum toxin A injection, were
      presented. A pair of studies addressed the importance of anatomic correction of
      pelvic organ prolapse in the treatment of overactive bladder syndrome. Nineteen
      abstracts are reviewed here.

PMID- 18042322
TI  - Antimuscarinics for the treatment of overactive bladder: a review of central
      nervous system effects.
AB  - Antimuscarinic drugs commonly used to treat overactive bladder are often
      associated with central nervous system (CNS) side effects including cognitive
      dysfunction, memory impairment, dizziness, fatigue, and headache. New agents show
      reduced CNS penetrance and better selectivity for the M3 muscarinic receptor.
      However, changes associated with aging may lead to alterations in blood-brain
      barrier permeability. Therefore, use of antimuscarinics in the elderly or in
      patients with Alzheimer's disease presents a significant challenge. This review
      highlights muscarinic receptor distribution and function in the CNS, provides a
      description and incidence of CNS side effects with therapy, offers information
      specific to currently available agents, and describes the use of antimuscarinics
      in special populations including children, the elderly, and patients with
      Alzheimer's disease.

PMID- 18042323
TI  - Current and future techniques of neuromodulation for bladder dysfunction.
AB  - Recent increase in the use of neuromodulation for the treatment of urinary
      urgency and frequency, urge incontinence, and nonobstructive urinary retention
      has coincided with improved knowledge of micturition physiology and concurrent
      technologic advances in nerve stimulation. Currently, the most common technology
      for bladder neuromodulation involves stimulation through the S3 foramen, or
      sacral neuromodulation, although other techniques of neuromodulation continue to
      be explored. Despite many advances in neuromodulation, the exact mechanism of
      action remains uncertain. Additionally, which patients will respond to
      neuromodulation remains unclear, and although there is a standard method for
      testing, this procedure is invasive and expensive. As we continue to improve
      patient selection criteria and better understand the mechanism of action, the
      efficacy and patient satisfaction should continue to increase. Currently, most
      patients considered for implantation with a neuromodulator are those unresponsive
      to other conservative treatments for bladder dysfunction.

PMID- 18042324
TI  - Neuromodulation techniques: a comparison of available and new therapies.
AB  - Neuromodulation has become ever more common in the fields of urology and voiding
      dysfunction. Many therapeutic alternatives have emerged to increase effectiveness
      of these therapies and reduce morbidity and invasiveness. Each new modality needs
      to prove its efficacy in common indications for voiding dysfunction such as
      refractory urgency-frequency, urge incontinence, and perhaps urinary retention,
      as well as in select patient populations and subgroups. We need more information
      to broaden the applicability of neuromodulation to larger numbers of patients and
      conditions.

PMID- 18042325
TI  - The importance of risk factor reduction in erectile dysfunction.
AB  - Erectile dysfunction (ED) is associated with modifiable risk factors. Obesity,
      physical inactivity, and the metabolic syndrome increase the incidence of ED and
      markers of low-grade inflammation, which in turn are associated with endothelial
      dysfunction. Intensive intervention with lifestyle advice focusing on a healthy
      diet, weight loss, and increased physical activity benefits men with ED, reducing
      the markers of inflammation and improving endothelial function. Though
      phosphodiesterase type 5 inhibitors are highly effective in treating ED,
      lifestyle advice and aggressive risk reduction remain fundamental to the overall
      vascular good health of the individual.

PMID- 18042326
TI  - Testosterone, diabetes mellitus, and the metabolic syndrome.
AB  - Metabolic syndrome is characterized by insulin insensitivity, central obesity
      dyslipidemia, and hypertension. It is recognized as a risk factor for
      cardiovascular disease in men; by the time metabolic syndrome is diagnosed,
      however, most men already have entrenched cardiovascular disease. A reliable
      early warning sign is needed to alert physicians to those at risk for metabolic
      syndrome and cardiovascular disease. Low serum testosterone level has emerged as
      a reliable prognosticator of metabolic syndrome in men whose testosterone
      deficiency is genetic (Klinefelter syndrome), iatrogenic following surgery for
      testicular cancer, pharmacologically induced by gonadotropin-releasing hormone
      during prostate cancer treatment, or a natural consequence of aging. One third of
      men with type 2 diabetes mellitus are now recognized as testosterone deficient.
      Emerging evidence suggests that testosterone therapy may be able to reverse some
      aspects of metabolic syndrome.

PMID- 18042327
TI  - Central nervous system-acting agents and the treatment of erectile and sexual
      dysfunction.
AB  - Recent animal studies have resulted in newer central nervous system (CNS)-acting
      agents for the treatment of sexual dysfunction in men and women. CNS stimulation
      and control of sexual function primarily originates in the hypothalamus, medial
      preoptic area, and paraventricular nucleus. Neurotransmitters responsible for
      sexual function, such as serotonin, dopamine, and oxytocin, can be manipulated
      pharmacologically. Early clinical trials and use of apomorphine have shown
      limited success and acceptance among patients, especially after the introduction
      of agents with improved efficacy and tolerability such as phosphodiesterase type
      5 inhibitors. Newer CNS-acting agents such as bremelanotide show significant
      promise in bringing to clinical practice a group of centrally acting agents to
      supplement the treatment of erectile dysfunction. CNS-acting agents also show
      promise in treating female sexual dysfunction. Further, development of selective
      dopamine receptor agonists, melatonin agonists, and other CNS stimulatory or
      inhibitory agents may lead to improved treatment of sexual dysfunction in men and
      women.

PMID- 18042328
TI  - Dual implantation of penile and sphincter implants in the post-prostatectomy
      patient.
AB  - Despite major improvement in surgical techniques for radical pelvic surgery,
      including radical prostatectomy, major quality-of-life issues persist, such as
      postoperative erectile dysfunction and urinary incontinence. These two conditions
      have many common etiologies and often occur in the same patient. Patients with
      either of these conditions fail initial conservative or minimally invasive
      therapy and become candidates for prosthetic implants, such as artificial urinary
      sphincter and penile prosthesis. In the past three decades, there have been
      significant improvements in the mechanical properties of these devices, their
      functional capabilities, and surgical implantation techniques. Studies once
      suggested that implantation of both devices in one patient could lead to failure,
      but recent literature proves that patients benefit from simultaneous dual
      implantation. Specific benefits relate to shorter surgery time, with potentially
      lower infection rates. In this manuscript, we review the indications, techniques,
      merits, and safety of simultaneous dual implantation of the artificial urinary
      sphincter and penile prosthesis in the post-radical prostatectomy patient.

PMID- 18042329
TI  - Phosphodiesterase type 5 inhibitors, visual changes, and nonarteritic anterior
      ischemic optic neuropathy: is there a link?
AB  - Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute
      optic neuropathy and one of the most common causes of sudden vision loss in the
      elderly. Recently, NAION has been associated with the use of phosphodiesterase
      type 5 inhibitors (PDE5i) in men with erectile dysfunction (ED). A causal
      relationship could not be established given the large number of men safely using
      PDE5i and the limited number of NAION cases reported in these men. ED and NAION
      share common risk factors; therefore, some men with ED should be expected to
      develop NAION. However, sudden vision loss or decreased vision in one or both
      eyes demands immediate cessation of PDE5i use and urgent patient assessment. No
      causal relationship between PDE5i and the development of NAION exists for the
      moment, yet physicians should be aware of a possible adverse reaction and inform
      patients accordingly.

PMID- 18042330
TI  - Bicycle riding, perineal trauma, and erectile dysfunction: data and solutions.
AB  - Significant clinical and basic science advances in the field of sexual medicine
      have facilitated investigation of the link between endothelial dysfunction and
      erectile dysfunction. Most sexual medicine practitioners accept the premise that
      in aging men with risk factors such as increased waist circumference, diabetes,
      hypertension, hypogonadism, hypercholesterolemia, and insulin insensitivity, a
      higher prevalence of erectile dysfunction reflects systemic vasculopathy that
      often first presents as abnormal erectile function. Endothelial dysfunction in
      the pudendal, common penile, and cavernosal arterial bed can occur secondary to
      pelvic, perineal, or penile trauma in young men without traditional systemic
      vascular risk factors. Because some younger men with erectile dysfunction may
      have underlying vasculogenic erectile dysfunction, sexual medicine practitioners
      should perform sophisticated testing procedures to evaluate erectile function
      that can be reestablished with penile revascularization surgery.

PMID- 18042331
TI  - Efficacy of imiquimod as an adjunct to cryotherapy for actinic keratoses.
AB  - BACKGROUND: Cryotherapy is the standard of care for clinically apparent (target)
      actinic keratoses (AKs). Topical imiquimod may reduce initially inapparent or
      subclinical AKs. OBJECTIVE: We evaluated the potential of topical imiquimod to
      decrease subclinical AKs after cryotherapy of target AKs. METHODS: A randomized
      trial of imiquimod or vehicle twice weekly for 8 weeks following 3- to 5-second
      cryotherapy of target AKs within a 50 cm(2) field at the face or scalp was
      conducted. Efficacy outcomes included clearance of target, subclinical, and total
      AKs and proportions clear of AKs. Subjects with residual AKs were offered
      cryotherapy and open-label imiquimod twice weekly for 8 weeks. RESULTS: Sixty
      three subjects completed the randomized phase. At 12 weeks, target AK clearance
      was similar for imiquimod and vehicle (79% vs 76%), but fewer total AKs were
      noted for imiquimod (78 vs 116). This was due to a progressive reduction in
      subclinical AKs with imiquimod compared with a progressive increase with vehicle.
      More subjects treated with imiquimod achieved clearance of subclinical (58% vs
      34%; p = .06) and total (23% vs 9%; p = .21) AKs. CONCLUSION: Imiquimod
      postcryotherapy may increase clearance of subclinical and total AKs and
      proportions of subjects clear at 3 months. These findings require confirmation in
      larger controlled trials powered for statistical significance.

PMID- 18042332
TI  - Alefacept is safe and efficacious in the treatment of palmar plantar pustulosis.
AB  - BACKGROUND: Alefacept blocks T-cell activation and induces apoptosis of memory T
      cells. It improves psoriasis vulgaris and may induce prolonged remissions.
      Experience with alefacept in palmar plantar pustulosis (PPP) is limited.
      OBJECTIVE: The objective of the study was to observe the effectiveness and safety
      of alefacept in the treatment of PPP. METHODS: Alefacept was administered weekly
      for 16 weeks by intramuscular (IM) injection of 15 mg to 15 patients with
      moderate to very severe PPP. Patients were followed for an additional 12 weeks.
      RESULTS: Four weeks after 16 weeks of treatment, there was a 49.6% reduction in
      the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) and a
      38.6% and a 64.5% reduction in total and fresh pustules, respectively. Eight
      weeks after dosing, 53.3% achieved PPPASI 50, 26.7% achieved PPPASI 75, and one
      patient was clear. The mean percent reduction in total pustules and fresh
      pustules was 46.1% and 61.2%, respectively; 73% had no pain, 53% had no itching,
      and 80% had no functional impairment. The palms responded better than the soles.
      CONCLUSIONS: This pilot showed that 16 weeks of once-weekly alefacept 15 mg IM
      was safe, led to improvement in PPP in all 15 treated patients, and induced a
      remission in one patient. Larger double-blind studies are warranted.

PMID- 18042333
TI  - Association between proliferative scars and in-stent restenosis.
AB  - BACKGROUND: Keloid and hypertrophic scars are two types of proliferative scars at
      sites of cutaneous injury that form as a result of an abnormal wound-healing
      process. Proliferative scar formation after skin injury and restenosis after
      coronary stenting have common features. The aim of this study was to investigate
      the association of proliferative scars with coronary stent restenosis. METHODS:
      Patients with previous open heart surgery with median sternotomy who had coronary
      stenting after the surgery and were admitted for control angiography were
      included in the study. The patients were divided into two groups according to the
      presence or absence of proliferative scars. The primary end point was the
      incidence of angiographic restenosis in patient groups. RESULTS: The study group
      consisted of 80 patients (64 men; mean age 64 + or - 9 years). Twenty-three
      patients (29%) have a proliferative scar. In general, two groups were comparable
      with regard to baseline lipid profiles, demographics, and cardiovascular risk
      factors. Restenosis was significantly more prevalent in patients with
      proliferative scars than with controls (p = .04). By multivariate logistic
      regression analysis, stent length (odds ratio [OR] 1.12, p = .005), diabetes (OR
      3.3, p = .03), and proliferative scar (OR 4.2, p = .02) independently predicted
      in-stent restenosis. CONCLUSION: The findings of this study suggest that patients
      with proliferative scars may have a higher risk of in-stent restenosis.

PMID- 18042335
TI  - Observations on the procedural aspects and health effects of scarification in sub
      Saharan Africa.
AB  - BACKGROUND: Scarification involves cutting or making an incision into the skin
      and then allowing the wound to heal, leaving a permanent scar. The purpose of
      this article is to examine the origins of scarification and its social and
      medical significance in sub-Saharan Africa. METHODS: We conducted a computerized
      search in the MEDLINE electronic database with combinations of the following
      terms: scarification, tribal marks, keloid, hypertrophic scar, Africa, and sub
      Saharan Africa. Inclusion criteria were studies published in English involving
      human participants. We reviewed the bibliography of each article that met our
      inclusion criteria for additional relevant studies. We abstracted data on the
      historical, social, and medical aspects of scarification from eligible studies.
      RESULTS: This review of scarification in sub-Saharan Africa highlights the
      complex interplay that exists between biology and society. Photographs, artwork,
      and literary descriptions reveal that scarification results in hypertrophic or
      atrophic scars, although these types of scars are often mistakenly referred to as
      keloids. In terms of the procedural aspects of scarification, specific tools and
      substances were consistently used by various ethnic groups. Although much is
      known about the history of scarification as a form of identification in Africa,
      it appears that the practice also had medical applications. Scarification was
      used to treat conditions such as epilepsy, although it was also known to
      exacerbate conditions such as sarcoidosis, lichen planus, and psoriasis. Evolving
      cultural beliefs, in addition to the association of scarification with an
      increased risk of contracting hepatitis B and human immunodeficiency virus (HIV),
      are contemporary threats to this long-standing practice. CONCLUSIONS: Given the
      remarkably consistent appearance of scars that are described in the literature
      and depicted in images, scarification does not appear to be a random or
      accidental occurrence. Instead, it is a deliberate attempt to reproduce a custom
      that has been perfected after many years of practice in sub-Saharan Africa.

PMID- 18042334
TI  - Development and validation of a comprehensive acne severity scale.
AB  - BACKGROUND: Although more than 25 acne grading systems exist, only 2 are
      inclusive of truncal acne. There is neither a gold standard nor a consistently
      used standardized system. PURPOSE: Our purpose was to develop and validate an
      acne grading system incorporating severity at the face, chest, and back. METHODS:
      We developed a comprehensive acne severity scale (CASS) by modifying a
      preexisting facial acne scale, the Investigator Global Assessment, to include
      truncal acne. The validity and responsiveness of CASS grades were correlated with
      Leeds scores at baseline and after 6 months of standard acne treatment. RESULTS:
      Spearman correlations were significant between Leeds and CASS grades for the face
      (0.823), chest (0.854), and back (0.872), respectively (p < .001). After 6 months
      of therapy, changes in these scores were also significantly correlated (p < .001)
      at all three sites. CONCLUSION: Concurrent validity of CASS is demonstrated by a
      very strong correlation with Leeds grading. CASS is simpler to use than the Leeds
      system and more appropriate for translation of research trial results to clinical
      practice.

PMID- 18042336
TI  - Topical tacrolimus in the treatment of erosive pustular dermatosis of the scalp.
AB  - BACKGROUND: Erosive pustular dermatosis of the scalp (EPDS) is a rare condition
      characterized by chronic, sterile, pustular erosions leading to scarring
      alopecia. Although the etiology is unknown, it appears to be associated with
      ultraviolet light exposure and trauma. Histologic findings include nonspecific
      atrophy of the epidermis and chronic inflammation. CASE HISTORY: A 71-year-old
      female presented with a 1-year history of a boggy, erythematous, friable plaque
      on the vertex of her scalp. A diagnosis of EPDS was made based on presentation,
      negative cultures, and histologic findings. Initial therapy with intralesional
      and topical steroids and oral antibiotics resolved the inflamed plaques; however,
      steroid-induced atrophy became prominent after 5 months of use. The treatment was
      discontinued, resulting in recurrence of disease. Topical tacrolimus 0.1%
      ointment was initiated, which has been successfully controlling the lesions with
      reversal of skin atrophy and clinical evidence of hair growth. CONCLUSION: This
      is the fourth reported case of the successful treatment of EPDS with topical
      tacrolimus for the resolution of atrophy and the prevention of relapse of
      inflammation. Although its long-term use warrants close follow-up for side
      effects, tacrolimus may constitute a novel therapeutic option for the treatment
      of EPDS.

PMID- 18042338
TI  - [Mechanism and prevention of the coronary complications for noncardiac surgery].

PMID- 18042339
TI  - [Innovations in emergency management of chest pain with CT angiography].
AB  - Recent technological innovations modify the diagnosis opportunities of multislice
      CT angiography. Emergency chest pain management is therefore optimised and still
      oriented by clinical presentation. Aortic CT angiography allows the diagnosis and
      classification of aortic dissection or intramural haematoma. It also shows the
      extension to aortic thoracoabdominal branches and visceral involvement. Pulmonary
      embolism diagnosis will be completed by scanographic evaluation of its
      seriousness. Chest pain caused by pulmonary or digestive diseases will also be
      documented. A late phase imaging seems useful to diagnose acute myocardial
      pathology.

PMID- 18042340
TI  - [Allergy and refractory asthma: new etiological and treatment pathways].
AB  - Severe asthma is often refractory to standard treatments and presents real
      problems of management. It necessitates rigorous clinical procedures to identify
      the aggravating factors. Allergic factors probably play an important role but are
      often ignored; atopy is more often associated with mild or moderate asthma. The
      prevalence of severe refractory asthma is not known with any precision, in view
      of the lack of a consensus definition. Few studies have examined the role of
      allergic factors. From a pathophysiologic perspective, genetic factors are
      probably responsible for greater severity, and allergic response plays an
      important role in some severe asthma phenotypes. From an environmental
      perspective, some airborne allergens are associated with the refractory character
      of the disease. Molds such as Alternaria are, for example, implicated in the
      onset of asthma attacks, as are some occupational exposure. Better knowledge of
      the pathophysiology of refractory asthma and its allergic dimensions have made it
      possible to use new treatment agents, such as omalizumab. New treatment targets
      are being discovered and evaluated in this domain.

PMID- 18042341
TI  - [Current data on the treatment of chronic hepatitis B].
AB  - Despite the development of new therapeutic options, treatment of chronic
      hepatitis B remains a clinical challenge because of the need for long-term
      treatment in most patients. Treatment with pegylated interferon is the only
      option that allows a defined duration of treatment. Nonetheless, approximately
      70% of the patients treated do not have a prolonged treatment response. A variety
      of nucleoside analog viral polymerase (reverse transcriptase) inhibitors have
      been developed (lamivudine, adefovir dipivoxil, entecavir, telbivudine); they can
      be administered orally and are well tolerated. These antiviral agents effectively
      induce viral suppression, which is accompanied by an improvement in transaminases
      and hepatic histology. Nonetheless, the rates of HBe and HBs seroconversion
      remain low with nucleoside analogs, and the absence of these immunologic events
      necessitates prolonged antiretroviral treatment. Treatment with nucleoside
      analogs leads to selection of resistant mutant viruses. They therefore require
      close clinical and virologic follow-up to enable early screening for resistance
      and adaptation of treatment before the liver disease worsens. The development of
      these different treatment options has made possible very significant improvements
      in the management of patients with chronic hepatitis B, by preventing aggravation
      of liver disease in most of them.

PMID- 18042342
TI  - Inhibition of message for FcepsilonRI alpha chain blocks mast cell IL-4
      production induced by co-culture with Mycoplasma pneumoniae.
AB  - We have previously described the activation of RBL-2H3 mast cells for IL-4
      production by Mycoplasma pneumoniae but the mechanism remains unclear. M.
      pneumoniae binds eukaryotic cells primarily through sialoglycoproteins on the
      target cell surface. This study was undertaken to determine whether the sialated
      FcepsilonRI alpha chain on RBL cells is important for M. pneumoniae-induced IL-4
      production. We found that IgE-mediated IL-4 release by a series of RBL sublines
      correlated with the release induced by M. pneumoniae. Further, aggregation of
      FcgammaRII (CD32) in RBL cells using a monoclonal antibody inhibited both IgE
      mediated and mycoplasma-induced IL-4 production, providing further evidence for
      an Fc receptor-mediated mechanism of activation. To examine the role of
      FcepsilonRI in mycoplasma-induced IL-4 release, we created stably transfected RBL
      sublines using a vector expressing a short hairpin sequence designed to inhibit
      message for the FcepsilonRI alpha chain. IgE-induced IL-4 production by the
      transfected sublines was reduced in similar proportion to the degree of message
      suppression. M. pneumoniae-induced IL-4 production in the four transfected
      sublines was completely blocked in contrast to results with the controls or
      parent RBL cells. We conclude that the heavily glycosylated FcepsilonRI alpha
      chain is required for activation of mast cells for IL-4 production by M.
      pneumoniae.

PMID- 18042343
TI  - Transgenerational epigenetic programming of the embryonic testis transcriptome.
AB  - Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex
      determination appears to promote an epigenetic reprogramming of the male germ
      line that is associated with transgenerational adult-onset disease states.
      Transgenerational effects on the embryonic day 16 (E16) testis demonstrated
      reproducible changes in the testis transcriptome for multiple generations (F1
      F3). The expression of 196 genes was found to be influenced, with the majority of
      gene expression being decreased or silenced. Dramatic changes in the gene
      expression of methyltransferases during gonadal sex determination were observed
      in the F1 and F2 vinclozolin generation (E16) embryonic testis, but the majority
      returned to control-generation levels by the F3 generation. The most dramatic
      effects were on the germ-line-associated Dnmt3A and Dnmt3L isoforms. Observations
      demonstrate that an embryonic exposure to vinclozolin appears to promote an
      epigenetic reprogramming of the male germ line that correlates with
      transgenerational alterations in the testis transcriptome in subsequent
      generations.

PMID- 18042344
TI  - The risky business of ageing.
AB  - This commentary reflects on the work by Chen and colleagues which compares the
      effect of an immune challenge in hippocampus and hippocampal-dependent function
      young and aged mice.

PMID- 18042345
TI  - PCR-based identification of short deletion/insertions and single nucleotide
      substitutions in genotyping of splotch (Pax3sp) and truncate (Nototc) mouse
      mutants.
AB  - Splotch (Pax3(sp)) and truncate (Noto(tc)) are spontaneously arisen mouse mutants
      with disturbed embryo development. Splotch carries a Pax3 mutation and it is
      characterized by the neural tube defect. Corresponding mutation in human causes
      Waardenburg syndrome. Truncate is Noto mutant with disturbed development of the
      caudal notochord. In order to establish easy genotyping procedure of these
      mutations, it was tested whether simple PCRs with single primer pairs could be
      used for this purpose. As it was necessary to differentiate sequence variants on
      the scale of one to several nucleotides, the approach referred to as "3' variable
      primer ends" was applied. The method was based on the presence of discriminating
      nucleotides at the 3' end of the primer sequence. This approach was successfully
      applied in genotyping adult mice and embryos of splotch with a 6 bp
      deletion/insertion and truncate with a single nucleotide substitution. Described
      genotyping approach facilitates recognizing of these mutations and it could be in
      general used for detection of sequence differences in one to several nucleotides.

PMID- 18042347
TI  - GABAA/Benzodiazepine receptor binding in patients with schizophrenia using
      [11C]Ro15-4513, a radioligand with relatively high affinity for alpha5 subunit.
AB  - Dysfunction of the GABA system is considered to play a role in the pathology of
      schizophrenia. Individual subunits of GABA(A)/Benzodiazepine (BZ) receptor
      complex have been revealed to have different functional properties. alpha5
      subunit was reported to be related to learning and memory. Changes of alpha5
      subunit in schizophrenia were reported in postmortem studies, but the results
      were inconsistent. In this study, we examined GABA(A)/BZ receptor using
      [(11)C]Ro15-4513, which has relatively high affinity for alpha5 subunit, and its
      relation to clinical symptoms in patients with schizophrenia. [(11)C]Ro15-4513
      bindings of 11 patients with schizophrenia (6 drug-naive and 5 drug-free) were
      compared with those of 12 age-matched healthy control subjects using positron
      emission tomography. Symptoms were assessed using the Positive and Negative
      Syndrome Scale. [(11)C]Ro15-4513 binding was quantified by binding potential (BP)
      obtained by the reference tissue model. [(11)C]Ro15-4513 binding in the
      prefrontal cortex and hippocampus was negatively correlated with negative symptom
      scores in patients with schizophrenia, although there was no significant
      difference in BP between patients and controls. GABA(A)/BZ receptor including
      alpha5 subunit in the prefrontal cortex and hippocampus might be involved in the
      pathophysiology of negative symptoms of schizophrenia.

PMID- 18042346
TI  - The RGK family of GTP-binding proteins: regulators of voltage-dependent calcium
      channels and cytoskeleton remodeling.
AB  - RGK proteins constitute a novel subfamily of small Ras-related proteins that
      function as potent inhibitors of voltage-dependent (VDCC) Ca(2+) channels and
      regulators of actin cytoskeletal dynamics. Within the larger Ras superfamily, RGK
      proteins have distinct regulatory and structural characteristics, including
      nonconservative amino acid substitutions within regions known to participate in
      nucleotide binding and hydrolysis and a C-terminal extension that contains
      conserved regulatory sites which control both subcellular localization and
      function. RGK GTPases interact with the VDCC beta-subunit (Ca(V)beta) and inhibit
      Rho/Rho kinase signaling to regulate VDCC activity and the cytoskeleton
      respectively. Binding of both calmodulin and 14-3-3 to RGK proteins, and
      regulation by phosphorylation controls cellular trafficking and the downstream
      signaling of RGK proteins, suggesting that a complex interplay between
      interacting protein factors and trafficking contribute to their regulation.

PMID- 18042348
TI  - Increased superior temporal activation associated with external misattributions
      of self-generated speech in schizophrenia.

PMID- 18042349
TI  - Meta-regression analysis using latitude as moderator of paternal age related
      schizophrenia risk: high ambient temperature induced de novo mutations or is it
      related to the cold?
AB  - While the season of birth, latitude and first admission effects suggest higher
      risk of schizophrenia with cold climate, the high ambient temperature induced de
      novo mutation hypothesis suggests the opposite. We conducted a systematic review
      and meta-analysis (4 case-control studies and 5 cohort studies). We used annual
      mean daily temperature and latitude of study sites as direct and indirect
      measures of ambient temperature respectively. Using case-control studies
      conducted in the Northern hemisphere for meta-regression, high latitude and low
      ambient temperature were found to increase paternal age related schizophrenia
      risk significantly. More research is needed to support the de novo mutation
      hypothesis.

PMID- 18042350
TI  - Relationships between white matter metabolite abnormalities, cognitive and social
      functioning in elderly schizophrenic subjects.

PMID- 18042351
TI  - Olfactory identification performance in individuals with psychometrically-defined
      schizotypy.
AB  - While deficits in olfaction have been well documented in individuals with
      schizophrenia, less research has focused on olfactory identification performance
      in psychometrically-defined schizotypy. The Abbreviated Schizotypal Personality
      Questionnaire was used to define two groups of 26 individuals (62% female)
      reporting high and average levels of schizotypy. Overall group differences on the
      Brief Smell Identification Test did not approach statistical significance, and
      this finding did not differ within either sex. The findings may reflect either
      the abbreviated nature of the measures used, or a lack of reliable olfactory
      performance differences in schizotypy.

PMID- 18042352
TI  - pannier encodes two structurally related isoforms that are differentially
      expressed during Drosophila development and display distinct functions during
      thorax patterning.
AB  - Previous studies have shown that the pannier (pnr) gene of Drosophila encodes a
      GATA transcription factor which is involved in various biological processes,
      including heart development, dorsal closure during embryogenesis as well as
      neurogenesis and regulation of wingless (wg) expression during imaginal
      development. We demonstrate here that pnr encodes two highly related isoforms
      that share functional domains but are differentially expressed during
      development. Moreover, we describe two genomic regions of the pnr locus that
      drive expression of a reporter in transgenic flies in patterns that recapitulate
      essential features of the expression of the isoforms, suggesting that these
      regions encompass crucial regulatory elements. These elements contain, in
      particular, sequences mediating regulation of expression by Decapentaplegic (Dpp)
      signaling, during both embryogenesis and imaginal development. Analysis of pnr
      alleles reveals that the isoforms differentially regulate expression of both wg
      and proneural achaete/scute (as/sc) targets during imaginal development. Pnr
      function has been demonstrated to be necessary both for activation of wg and,
      together with U-shaped (Ush), for its repression in the dorsal-most region of the
      presumptive notum. Expression of the isoforms define distinct longitudinal
      domains and, in this regard, we importantly show that the dual function of pnr
      during regulation of wg is achieved by one isoform repressing expression of the
      morphogen in the dorsal-most region of the disc while the other laterally
      promotes activation of the notal wg expression. Our study provides novel insights
      into pnr function during Drosophila development and extends our knowledge of the
      roles of prepattern factors during thorax patterning.

PMID- 18042353
TI  - Activin signaling limits the competence for retinal regeneration from the
      pigmented epithelium.
AB  - Regeneration of the retina in amphibians is initiated by the transdifferentiation
      of the retinal pigmented epithelium (RPE) into neural progenitors. A similar
      process occurs in the early embryonic chick, but the RPE soon loses this ability.
      The factors that limit the competence of RPE cells to regenerate neural retina
      are not understood; however, factors normally involved in the development of the
      eye (i.e. FGF and Pax6) have also been implicated in transdifferentiation.
      Therefore, we tested whether activin, a TGFbeta family signaling protein shown to
      be important in RPE development, contributes to the loss in competence of the RPE
      to regenerate retina. We have found that addition of activin blocks regeneration
      from the RPE, even during stages when the cells are competent. Conversely, a
      small molecule inhibitor of the activin/TGFbeta/nodal receptors can delay, and
      even reverse, the developmental restriction in FGF-stimulated neural retinal
      regeneration.

PMID- 18042354
TI  - New insights offered by a computational model of deep brain stimulation.
AB  - Deep brain stimulation (DBS) is a standard neurosurgical procedure used to treat
      motor symptoms in about 5% of patients with Parkinson's disease (PD). Despite the
      indisputable success of this procedure, the biological mechanisms underlying the
      clinical benefits of DBS have not yet been fully elucidated. The paper starts
      with a brief review on the use of DBS to treat PD symptoms. The second section
      introduces a computational model based on the population density approach and the
      Izhikevich neuron model. We explain why this model is appropriate for
      investigating macroscopic network effects and exploring the physiological
      mechanisms which respond to this treatment strategy (i.e., DBS). Finally, we
      present new insights into the ways this computational model may help to elucidate
      the dynamic network effects produced in a cerebral structure when DBS is applied.

PMID- 18042355
TI  - Coding processes involved in the cortical representation of complex tactile
      stimuli.
AB  - To understand how information is coded in the primary somatosensory cortex (S1)
      we need to decipher the relationship between neural activity and tactile stimuli.
      Such a relationship can be formally measured by mutual information. The present
      study was designed to determine how S1 neuronal populations code for the
      multidimensional kinetic features (i.e. random, time-varying patterns of force)
      of complex tactile stimuli, applied at different locations of the rat forepaw.
      More precisely, the stimulus localization and feature extraction were analyzed as
      two independent processes, using both rate coding and temporal coding strategies.
      To model the process of stimulus kinetic feature extraction, multidimensional
      stimuli were projected onto lower dimensional subspace and then clustered
      according to their similarity. Different combinations of stimuli clustering were
      applied to differentiate each stimulus identification process. Information
      analyses show that both processes are synergistic, this synergy is enhanced
      within the temporal coding framework. The stimulus localization process is faster
      than the stimulus feature extraction process. The latter provides more
      information quantity with rate coding strategy, whereas the localization process
      maximizes the mutual information within the temporal coding framework. Therefore,
      combining mutual information analysis with robust clustering of complex stimuli
      provides a framework to study neural coding mechanisms related to complex stimuli
      discrimination.

PMID- 18042356
TI  - From physiological principles to computational models of the cortex.
AB  - Understanding the brain goes through the assimilation of an increasing amount of
      biological data going from single cell recording to brain imaging studies and
      behavioral analysis. The description of cognition at these three levels provides
      us with a grid of analysis that can be exploited for the design of computational
      models. Beyond data related to specific tasks to be emulated by models, each of
      these levels also lays emphasis on principles of computation that must be obeyed
      to really implement biologically inspired computations. Similarly, the advantages
      of such a joint approach are twofold: computational models are a powerful tool to
      experiment brain theories and assess them on the implementation of realistic
      tasks, such as visual search tasks. They are also a way to explore and exploit an
      original formalism of asynchronous, distributed and adaptive computations with
      such precious properties as self-organization, emergence, robustness and more
      generally abilities to cope with an intelligent interaction with the world. In
      this article, we first discuss three levels at which a cortical circuit might be
      observed to provide a modeler with sufficient information to design a
      computational model and illustrate this principle with an application to the
      control of visual attention.

PMID- 18042357
TI  - Effects of Hebbian learning on the dynamics and structure of random networks with
      inhibitory and excitatory neurons.
AB  - The aim of the present paper is to study the effects of Hebbian learning in
      random recurrent neural networks with biological connectivity, i.e. sparse
      connections and separate populations of excitatory and inhibitory neurons. We
      furthermore consider that the neuron dynamics may occur at a (shorter) time scale
      than synaptic plasticity and consider the possibility of learning rules with
      passive forgetting. We show that the application of such Hebbian learning leads
      to drastic changes in the network dynamics and structure. In particular, the
      learning rule contracts the norm of the weight matrix and yields a rapid decay of
      the dynamics complexity and entropy. In other words, the network is rewired by
      Hebbian learning into a new synaptic structure that emerges with learning on the
      basis of the correlations that progressively build up between neurons. We also
      observe that, within this emerging structure, the strongest synapses organize as
      a small-world network. The second effect of the decay of the weight matrix
      spectral radius consists in a rapid contraction of the spectral radius of the
      Jacobian matrix. This drives the system through the "edge of chaos" where
      sensitivity to the input pattern is maximal. Taken together, this scenario is
      remarkably predicted by theoretical arguments derived from dynamical systems and
      graph theory.

PMID- 18042358
TI  - Modeling spatial integration in the ocular following response using a
      probabilistic framework.
AB  - The machinery behind the visual perception of motion and the subsequent sensori
      motor transformation, such as in ocular following response (OFR), is confronted
      to uncertainties which are efficiently resolved in the primate's visual system.
      We may understand this response as an ideal observer in a probabilistic framework
      by using Bayesian theory [Weiss, Y., Simoncelli, E.P., Adelson, E.H., 2002.
      Motion illusions as optimal percepts. Nature Neuroscience, 5(6), 598-604,
      doi:10.1038/nn858] which we previously proved to be successfully adapted to model
      the OFR for different levels of noise with full field gratings. More recent
      experiments of OFR have used disk gratings and bipartite stimuli which are
      optimized to study the dynamics of center-surround integration. We quantified two
      main characteristics of the spatial integration of motion: (i) a finite optimal
      stimulus size for driving OFR, surrounded by an antagonistic modulation and (ii)
      a direction selective suppressive effect of the surround on the contrast gain
      control of the central stimuli [Barthelemy, F.V., Vanzetta, I., Masson, G.S.,
      2006. Behavioral receptive field for ocular following in humans: dynamics of
      spatial summation and center-surround interactions. Journal of Neurophysiology,
      (95), 3712-3726, doi:10.1152/jn.00112.2006]. Herein, we extended the ideal
      observer model to simulate the spatial integration of the different local motion
      cues within a probabilistic representation. We present analytical results which
      show that the hypothesis of independence of local measures can describe the
      spatial integration of the motion signal. Within this framework, we successfully
      accounted for the contrast gain control mechanisms observed in the behavioral
      data for center-surround stimuli. However, another inhibitory mechanism had to be
      added to account for suppressive effects of the surround.

PMID- 18042359
TI  - Fatty acid profile of the erythrocyte membrane preceding development of Type 2
      diabetes mellitus.
AB  - BACKGROUND AND AIMS: The respective roles of dietary fatty acids in the
      pathogenesis of diabetes are as yet unclear. Erythrocyte membrane fatty acid
      (EMFA) composition may provide an estimate of dietary fatty acid intake. This
      study investigates the relation between EMFA composition and development of Type
      2 diabetes mellitus. METHODS AND RESULTS: In a nested case-referent design we
      studied 159 individuals tested as non-diabetic at baseline who after a mean
      observation time of 5.4+/-2.6years were diagnosed with Type 2 diabetes mellitus
      and 291 sex- and age-matched referents. Higher proportions of pentadecanoic acid
      (15:0) and heptadecanoic acid (17:0) were associated with a lower risk of
      diabetes. In accordance with earlier findings, higher proportions of palmitoleic
      (16:1 n-7), dihomo-gamma-linolenic (20:3 n-6) and adrenic (22:4 n-6) acids were
      associated with increased risk, whereas linoleic (18:2 n-6) and clupanodonic
      (22:5 n-3) acids were inversely associated with diabetes. After adjustment for
      BMI, HbA1c, alcohol intake, smoking and physical activity the only significant
      predictors were 15:0 and 17:0 as protective factors and 22:4 n6 as risk factor.
      CONCLUSION: In accordance with previous studies, our results indicate that EMFA
      patterns predict development of Type 2 diabetes mellitus. The inverse association
      with two saturated fatty acids, previously shown to reflect consumption of dairy
      products, is a new finding.

PMID- 18042360
TI  - Hospital admissions and length of stay for coronary disease in an Aboriginal
      cohort.
AB  - BACKGROUND AND AIMS: Coronary disease (CHD)-related hospital admission is more
      common among indigenous than non-indigenous Australians. We aimed to identify
      predictors of hospital admission potentially useful in planning prevention
      programs. METHODS AND RESULTS: Length of stay (LOS), interval between, and number
      of recurrent admissions were modelled with proportional hazards or negative
      binomial models using lifestyle data recorded in 1988-1989 among Aborigines (256
      women, 258 men, aged 15-88years) linked to hospital records to 2002. Among 106
      Aborigines with CHD, hypertension (hazard ratio (HR) 1.69, 95% CI 1.05-2.73);
      smoking (HR 1.90, 95% CI 1.02-3.53); consuming processed meat >4 times/month (HR
      1.81, 95% CI 1.01-3.24); >6 eggs/week (HR 1.73, 95% CI 1.03-2.94); and lower
      intake of alcohol (HR 0.54, 95% CI 0.35-0.83) predicted LOS. Eating eggs (HR
      1.05, 95% CI 1.01-1.09) and bush meats > or =7 times/month (HR 0.46, 95% CI 0.23
      0.92) predicted interval between recurrent admissions. Hypertension (IRR 4.07;
      95% CI 1.32-12.52), being an ex-drinker (IRR 6.60, 95% CI 2.30-19.00), eating red
      meat >6 times/week (IRR 0.98, 95% CI 0.97-0.99), bush meats >7 times/month (IRR
      0.26, 95% CI 0.10-0.67), and adding salt to meals (IRR 3.16, 95% CI 1.12-8.92)
      predicted number of admissions. CONCLUSION: Hypertension, alcohol drinking,
      smoking, and diet influence hospital admissions for CHD in Aboriginal
      Australians.

PMID- 18042361
TI  - Relationship between von Willebrand factor, cholesterol and triglycerides in non
      diabetic subjects.

PMID- 18042362
TI  - Methoxy poly(ethylene glycol)--low molecular weight linear polyethylenimine
      derived copolymers enable polyplex shielding.
AB  - Targeted gene delivery relies on the development of materials that allow for the
      formation of small neutrally charged particles of sufficient colloidal stability
      preventing non-specific interactions with cells. In order to identify a copolymer
      composition that combines adequate plasmid DNA (pDNA) compaction with an
      efficient charge-shielding effect, we synthesized a series of copolymers by
      covalent linkage of activated 5 or 20 kDa linear methoxy poly(ethylene glycol)
      (mPEG) or 10 kDa two-arm-mPEG to non-toxic low molecular weight (2.6 and 4.6 kDa)
      linear polyethylenimine (lPEI) at different molar ratios (mPEG-lPEI copolymers).
      All of the copolymers condensed pEGFP-N1 pDNA to form nanoparticles with
      hydrodynamic diameters between 150 and 420 nm - sizes that were maintained for
      the entire duration of measurement. PEGylated complexes exhibited a reduced
      particle stability in comparison to the unmodified lPEI-pDNA polyplexes,
      determined by gel retardation assays and DNase I experiments. Copolymer-pDNA
      complexes exhibited a zeta potential between -4 and 6 mV, strongly depending on
      the dispersion medium applied (0.15M NaCl or 5% glucose supplemented with serum
      free cell culture medium). The transfection efficacy, determined in CHO-K1
      (between 0.28+/-0.08% and 1.92+/-0.46%) and HeLa (between 1.02+/-0.19% and 3.53+/
      0.30%) cells, was significantly reduced compared to lPEI-pDNA particles (between
      3.2+/-1.3% and 38.8+/-5.5%). The architecture of the copolymer, the molecular
      weight of the lPEI residue, and the supplementation of endosomolytic agents
      (saccharose, chloroquine) all failed to impact the efficacy of gene transfer.
      Uptake studies, based on Confocal Laser Scanning Microscopy (CLSM) imaging and
      flow cytometry analysis, suggest that the use of mPEG5/3-lPEI2.6, mPEG10/2
      lPEI2.6, and mPEG20-lPEI4.6 lowers unspecific internalization of the
      corresponding transfection complexes. This provides an ideal basis for the
      development of transfection vehicles for targeted gene transfer.

PMID- 18042363
TI  - The anion exchanger Ae2 is required for enamel maturation in mouse teeth.
AB  - One of the mechanisms by which epithelial cells regulate intracellular pH is
      exchanging bicarbonate for Cl(-). We tested the hypothesis that in ameloblasts
      the anion exchanger-2 (Ae2) is involved in pH regulation during maturation stage
      amelogenesis. Quantitative X-ray microprobe mineral content analysis, scanning
      electron microscopy, histology, micro-computed tomography and Ae2 immuno
      localisation analyses were applied to Ae2-deficient and wild-type mouse
      mandibles. Immuno-localisation of Ae2 in wild-type mouse incisors showed a very
      strong expression of Ae2 in the basolateral membranes of the maturation stage
      ameloblasts. Strikingly, zones of contiguous ameloblasts were found within the
      maturation stage in which Ae2 expression was extremely low as opposed to
      neighbouring cells. Maturation stage ameloblasts of the Ae2(a,b)(-/-) mice failed
      to stain for Ae2 and showed progressive disorganisation as enamel development
      advanced. Maturation stage enamel of the Ae2(a,b)(-/-) mice contained
      substantially less mineral and more protein than wild-type enamel as determined
      by quantitative X-ray microanalysis. Incisor enamel was more severely affected
      than molar enamel. Scanning electron microscopy revealed that the rod-inter-rod
      structures of the Ae2(a,b)(-/-) mice incisor enamel were absent. Mineral content
      of dentine and bone of Ae2(a,b)(-/-) mice was not significantly different from
      wild-type mice. The enamel from knockout mouse teeth wore down much faster than
      that from wild-type litter mates. Basolateral bicarbonate secretion via the
      anionic exchanger Ae2 is essential for mineral growth in the maturation stage
      enamel. The observed zonal expression of Ae2 in the maturation stage ameloblasts
      is in line with a model for cyclic proton secretion during maturation stage
      amelogenesis.

PMID- 18042364
TI  - TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin and
      increases fibronectin matrix assembly.
AB  - Human plasma fibronectin binds with high affinity to the inflammation-induced
      secreted protein TSG-6. Fibronectin binds to the CUB_C domain of TSG-6 but not to
      its Link module. TSG-6 can thus act as a bridging molecule to facilitate
      fibronectin association with the TSG-6 Link module ligand thrombospondin-1.
      Fibronectin binding to TSG-6 is divalent cation-independent and is conserved in
      cellular fibronectins. Based on competition binding studies using recombinant and
      proteolytic fragments of fibronectin, TSG-6 binding localizes to type III repeats
      9-14 of fibronectin. This region of fibronectin contains the Arg-Gly-Asp sequence
      recognized by alpha5beta1 integrin, but deletion of that sequence does not
      prevent TSG-6 binding, and TSG-6 does not inhibit cell adhesion on fibronectin
      substrates mediated by this integrin. This region of fibronectin is also involved
      in fibronectin matrix assembly, and addition of TSG-6 enhances exogenous and
      endogenous fibronectin matrix assembly by human fibroblasts. Therefore, TSG-6 is
      a high affinity ligand that can mediate fibronectin interactions with other
      matrix components and modulate some interactions of fibronectin with cells.

PMID- 18042365
TI  - Fat-1 transgenic mice: a new model for omega-3 research.
AB  - An appropriate animal model that can eliminate confounding factors of diet would
      be very helpful for evaluation of the health effects of nutrients such as n-3
      fatty acids. We recently generated a fat-1 transgenic mouse expressing the
      Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase that
      converts n-6 to n-3 fatty acids (which is absent in mammals). The fat-1
      transgenic mice are capable of producing n-3 fatty acids from the n-6 type,
      leading to abundant n-3 fatty acids with reduced levels of n-6 fatty acids in
      their organs and tissues, without the need of a dietary n-3 supply. Feeding an
      identical diet (high in n-6) to the transgenic and wild-type littermates can
      produce different fatty acid profiles in these animals. Thus, this model allows
      well-controlled studies to be performed, without the interference of the
      potential confounding factors of diet. The transgenic mice are now being used
      widely and are emerging as a new tool for studying the benefits of n-3 fatty
      acids and the molecular mechanisms of their action.

PMID- 18042366
TI  - Antimanic therapies target brain arachidonic acid signaling: lessons learned
      about the regulation of brain fatty acid metabolism.
AB  - Bipolar disorder is a major medical, social and economic burden worldwide.
      However, the biochemical basis of the disorder and the mechanisms of action of
      effective antibipolar disorder drugs remain elusive. In this paper, we review how
      combining a kinetic approach to studying the turnover of fatty acids within brain
      phospholipids of unanesthetized rats along with chronic administration of
      antimanic drugs (lithium, valproate and carbamazepine) at therapeutically
      relevant doses, shows that the brain arachidonic acid cascade is a common target
      of these drugs. The overlapping effects of the three drugs are decreased turnover
      of arachidonic acid but not of docosahexaenoic acid in rat brain phospholipids,
      and decreased brain cyclooxygenase-2 and prostaglandin E(2). Whereas lithium and
      carbamazepine target the transcription of the arachidonic acid-selective calcium
      dependent cytosolic phospholipase A(2), valproate is a non-competitive inhibitor
      of an arachidonic acid-selective acyl-CoA synthetase. Two potential models of
      bipolar disorder, chronic N-methyl-d-aspartate and n-3 polyunsaturated fatty acid
      deprivation, opposite to the antimanic drugs, increase the turnover and markers
      of the arachidonic acid cascade in rat brain. These observations support the
      hypothesis proposed by Rapoport and colleagues that the arachidonic acid cascade
      is a common target of mood stabilizers and that by targeting substrate-specific
      enzymes the turnover of individual fatty acids can be regulated within the brain.

PMID- 18042367
TI  - Modulation of T-cell signalling by non-esterified fatty acids.
AB  - Polyunsaturated fatty acids (PUFAs) have been shown to be immunosuppressive. In
      particular, they can decrease important T-cell functions that may have a profound
      impact on the acquired immune response. Several mechanisms may explain the
      immunosuppressive properties of PUFAs. Here we review the mechanisms by which
      they interfere with T-cell activation. PUFAs affect lipid rafts composition and
      function that play an essential role in T-cell signalling. The possible
      physiological and pathological significances of this immunomodulation by PUFAs
      are discussed. Further mechanistic studies and randomized controlled clinical
      trials are needed to assess more accurately their effects in healthy and
      pathological states.

PMID- 18042369
TI  - Multi-objective optimization of solid waste flows: environmentally sustainable
      strategies for municipalities.
AB  - An approach to sustainable municipal solid waste (MSW) management is presented,
      with the aim of supporting the decision on the optimal flows of solid waste sent
      to landfill, recycling and different types of treatment plants, whose sizes are
      also decision variables. This problem is modeled with a non-linear, multi
      objective formulation. Specifically, four objectives to be minimized have been
      taken into account, which are related to economic costs, unrecycled waste,
      sanitary landfill disposal and environmental impact (incinerator emissions). An
      interactive reference point procedure has been developed to support decision
      making; these methods are considered appropriate for multi-objective decision
      problems in environmental applications. In addition, interactive methods are
      generally preferred by decision makers as they can be directly involved in the
      various steps of the decision process. Some results deriving from the application
      of the proposed procedure are presented. The application of the procedure is
      exemplified by considering the interaction with two different decision makers who
      are assumed to be in charge of planning the MSW system in the municipality of
      Genova (Italy).

PMID- 18042368
TI  - n-3 Fatty acids modulate brain glucose transport in endothelial cells of the
      blood-brain barrier.
AB  - We have previously shown that glucose utilization and glucose transport were
      impaired in the brain of rats made deficient in n-3 polyunsaturated fatty acids
      (PUFA). The present study examines whether n-3 PUFA affect the expression of
      glucose transporter GLUT1 and glucose transport activity in the endothelial cells
      of the blood-brain barrier. GLUT1 expression in the cerebral cortex microvessels
      of rats fed different amounts of n-3 PUFA (low vs. adequate vs. high) was
      studied. In parallel, the glucose uptake was measured in primary cultures of rat
      brain endothelial cells (RBEC) exposed to supplemental long chain n-3 PUFA,
      docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, or to arachidonic acid
      (AA). Western immunoblotting analysis showed that endothelial GLUT1 significantly
      decreased (-23%) in the n-3 PUFA-deficient microvessels compared to control ones,
      whereas it increased (+35%) in the microvessels of rats fed the high n-3 PUFA
      diet. In addition, binding of cytochalasin B indicated that the maximum binding
      to GLUT1 (Bmax) was reduced in deficient rats. Incubation of RBEC with 15 microM
      DHA induced the membrane DHA to increase at a level approaching that of cerebral
      microvessels isolated from rats fed the high n-3 diet. Supplementation of RBEC
      with DHA or EPA increased the [(3)H]-3-O-methylglucose uptake (reflecting the
      basal glucose transport) by 35% and 50%, respectively, while AA had no effect. In
      conclusion, we suggest that n-3 PUFA can modulate the brain glucose transport in
      endothelial cells of the blood-brain barrier, possibly via changes in GLUT1
      protein expression and activity.

PMID- 18042370
TI  - Electronic scraps--recovering of valuable materials from parallel wire cables.
AB  - Every year, the number of discarded electro-electronic products is increasing.
      For this reason recycling is needed, to avoid wasting non-renewable natural
      resources. The objective of this work is to study the recycling of materials from
      parallel wire cable through unit operations of mineral processing. Parallel wire
      cables are basically composed of polymer and copper. The following unit
      operations were tested: grinding, size classification, dense medium separation,
      electrostatic separation, scrubbing, panning, and elutriation. It was observed
      that the operations used obtained copper and PVC concentrates with a low degree
      of cross contamination. It was concluded that total liberation of the materials
      was accomplished after grinding to less than 3 mm, using a cage mill. Separation
      using panning and elutriation presented the best results in terms of recovery and
      cross contamination.

PMID- 18042371
TI  - EU strategies and policies on soil and waste management to offset greenhouse gas
      emissions.
AB  - Climate change has become an important political priority in the environmental
      field, and beyond. To revert the increase in the Earth's temperature, developed
      country parties to the Kyoto Protocol committed to limit their greenhouse gas
      emissions. The 15 Member States that made up the European Community in 1997 have
      a combined reduction target of 8% in CO2-equivalent emissions in the period 2008
      2012 compared to 1990. The role of soil, both as a source and a sink for carbon,
      is particularly important. How can soil organic matter be maintained or
      increased? There is no single answer, and a broad range of options need to be
      explored. Among the different measures proposed, the promotion of organic input
      on arable land (crop residues, cover crops, farm yard manure, compost, sewage
      sludge) has been mentioned. The challenge is to ensure that organic wastes of
      good quality are used to increase soil organic matter in carbon depleted soils
      and that appropriate monitoring is established. On the waste management front,
      the European Commission intends to produce guidance for Member States on the
      management of biowaste that will take into account all related environmental
      issues, including soil aspects. As for monitoring, the European Commission has
      put forward legislation according to which Member States would have to identify
      the areas at risk of soil organic matter decline in their national territory.
      Such legislation should be regarded as a major step forward for Europe, as it
      would ensure a high level of soil protection across the Community. This
      development will have the potential to enable the kind of estimation, measurement
      or modelling of crop or grazing land management needed for accounting under
      Article 3.4 of the Kyoto Protocol.

PMID- 18042372
TI  - Assessment of chemical and biochemical stabilization of organic C in soils from
      the long-term experiments at Rothamsted (UK).
AB  - Biological and chemical stabilization of organic C was assessed in soils sampled
      from the long-term experiments at Rothamsted (UK), representing a wide range of
      carbon inputs and managements by extracting labile, non-humified organic matter
      (NH) and humic substances (HS). Four sequentially extracted humic substances
      fractions of soil organic matter (SOM) were extracted and characterized before
      and after a 215-day laboratory incubation at 25 degrees C from two arable soils,
      a woodland soil and an occasionally stubbed soil. The fractions corresponded to
      biochemically stabilised SOM extracted in 0.5M NaOH (free fulvic acids (FA) and
      humic acids (HA)) and chemically plus biochemically stabilised SOM extracted from
      the residue with 0.1M Na4P2O7 plus 0.1M NaOH (bound FA and HA). Our aim was to
      investigate the effects of chemical and biochemical stabilization on carbon
      sequestration. The non-humic to humic (NH/H) C ratio separated the soils into two
      distinct groups: arable soils (unless fertilised with farmyard manure) had an
      NH/H C ratio between 1.05 and 0.71, about twice that of the other soils (0.51
      0.26). During incubation a slow, but detectable, decrease in the NH/H C ratio
      occurred in soils of C input equivalent or lower to 4Mgha(-1)y(-1), whereas the
      ratio remained practically constant in the other soils. Before incubation the
      free to bound humic C ratio increased linearly (R2=0.91) with C inputs in the
      soils from the Broadbalk experiment and decreased during incubation, showing that
      biochemical stabilization is less effective than chemical stabilization in
      preserving humic C. Changes in delta13C and delta15N after incubation were
      confined to the free FA fractions. The delta13C of free FA increased by 1.48 and
      0.80 per thousand, respectively, in the stubbed and woodland soils, indicating a
      progressive biological transformation. On the contrary, a decrease was observed
      for the bound FA of both soils. Concomitantly, a Deltadelta15N of up to +3.52 per
      thousand was measured after incubation in the free FA fraction and a -2.58
      Deltadelta15N in the bound FA. These changes, which occurred during soil
      incubation in the absence of C inputs, indicate that free FA fractions were
      utilised by soil microorganisms, and bound FA were decomposed and replaced, in
      part, by newly synthesized FA. The 13CPMAS-TOSS NMR spectra of free HA extracted
      before and after 215 days of incubation were mostly unchanged. In contrast,
      changes were evident in bound HA and showed an increase in aromatic C after
      incubation.

PMID- 18042373
TI  - Effects of municipal solid waste compost and sewage sludge on chemical and
      spectroscopic properties of humic acids from a sandy Haplic Podzol and a clay
      loam Calcic Vertisol in Portugal.
AB  - The effects of amendment with municipal solid waste compost (MSWC) and
      anaerobically digested sewage sludge (SS) on the compositional and structural
      features of soil humic acids (HAs) were investigated. For this purpose, HAs were
      isolated from MSWC, SS, and two different Portuguese soils, a sandy Haplic Podzol
      and a clay loam Calcic Vertisol, which were either unamended or amended with MSWC
      or SS at a rate of 60 t ha(-1). The isolated HAs were analyzed for elemental and
      acidic functional group composition, and by ultraviolet/visible, Fourier
      transform infrared (FT IR), and fluorescence spectroscopies. The application of
      MSWC and especially SS to soils determined an increase of C, N, H, and S contents
      and E4/E6 ratios (i.e., ratios of absorbances at 465 and 665 nm), and a decrease
      of O, COOH, and phenolic OH contents and C/N, C/H, and O/C ratios of soil HAs.
      The FT IR and fluorescence results showed that the organic amendments, especially
      SS, caused an increase of the aliphatic character and a decrease of the degrees
      of aromatic polycondensation, polymerization, and humification of amended soil
      HAs. Both MSWC and SS affected more markedly the clayey soil HAs than the sandy
      soil HAs, possibly due to less extended mineralization processes and the
      protective action of clay minerals on amended soil HAs.

PMID- 18042374
TI  - Development of a temperature sensor array chip and a chip-based real-time PCR
      machine for DNA amplification efficiency-based quantification.
AB  - A temperature sensor array chip was developed to monitor the thermal cycling
      profiles of a polymerase chain reaction (PCR). DNA amplification efficiency of
      each cycle was estimated through temperature data to fit the stochastic model. A
      fluorescence detector system was constructed to detect the PCR amplifications of
      latter cycles, at which the fluorescence intensity passed the optical detection
      threshold. Through monitoring of both temperature and fluorescence, DNA
      amplification efficiency curve was completed for quantification. The Forster
      resonance energy transfer (FRET) was employed to detect the measurements of the
      PCR product amount at the reaction endpoint. The chip-based, real-time PCR
      machine was constructed to perform the amplification efficiency curve-based
      quantification method. This novel method achieved the absolute quantification of
      the Hepatitis B virus (HBV) DNA using a single sample without the construction of
      the standard curve. The coefficient of variation (CV) of the 15 replicates inter
      assay experiments was less than 5.87%. Compared with the CV values obtained from
      the commercial machine in the range of 4.33-14.56%, it is noted that CV values of
      the prototype with respect to the samples of different initial concentration
      ranging from 10(7) to 10(3)copies/ml are almost equable.

PMID- 18042375
TI  - The alpha1-adrenergic receptor antagonist doxazosin inhibits EGFR and NF-kappaB
      signalling to induce breast cancer cell apoptosis.
AB  - The selective alpha(1)-adrenergic receptor antagonist doxazosin (dox) has been
      reported to inhibit prostate cancer proliferation. We now demonstrate that dox
      treatment inhibits proliferation and induces apoptosis in breast cancer cells in
      vitro by mechanisms that do not wholly involve the alpha1-adrenergic receptor.
      Intriguingly, dox-treatment reduced phosphorylated EGFR expression, decreased
      pERK1/2 levels and decreased NF-kappaB, AP-1, SRE, E2F and CRE-mediated
      transcriptional activity. EGF- and TNFalpha treatment alone failed to block dox
      mediated breast cancer apoptotic effects, but combination of EGF and TNFalpha
      treatments completely abrogated dox-induced breast cancer cell apoptosis,
      indicating doxazosin inhibits both EGFR and NF-kappaB signalling pathways to
      induce breast cancer cell apoptosis. Doxazosin is proposed as a possible novel
      medical therapy for breast cancer.

PMID- 18042376
TI  - Atopic dysfunction and risk of central nervous system tumours in children.
AB  - Risk factors for central nervous system (CNS) tumours in children remain largely
      unknown. Evidence of an inverse relationship between atopy and tumour development
      exists in adults but little is known about childhood tumours. This study aims to
      examine the risk of childhood CNS tumours given a history of eczema and asthma.
      Cases of children diagnosed with CNS tumours (n=575) and controls (n=6292) from
      the UK Childhood Cancer Study (UKCCS) were analysed using conditional logistic
      regression comparing reported histories of allergic disease. Asthma was
      statistically significantly and negatively associated with all CNS tumours (odds
      ratios, OR 0.75, confidence of interval, CI(95%): 0.58-0.97), though this was not
      observed for eczema (OR 0.94, CI(95%): 0.74-1.18). Individuals who had suffered
      both asthma and eczema showed the most significant reduction in risk (OR 0.48,
      CI(95%): 0.28-0.81). Analysis by tumour subtype showed the strongest effect for
      the medulloblastoma/PNET group. These results may have a biological explanation
      with raised immunosurveillance in atopic individuals protecting against the
      development of brain tumours. Alternative explanations might include bias,
      reverse causality or confounding.

PMID- 18042377
TI  - Surgical treatment of rectal cancer after neoadjuvant chemoradiation. Where are
      we going?
AB  - Anterior resection of the rectum and abdominoperineal resection with total
      mesorectal excision represent the standard surgical approach after preoperative
      chemoradiation in rectal cancer. Many clinical trials seem to validate
      laparoscopic approach, even if long-term outcome has not been still reported.
      Some authors recently focused their research on organ-saving surgery, either
      local excision or non-operative treatment. In this paper we present a brief
      revision of what rectal cancer treatment is reaching.

PMID- 18042378
TI  - Laparoscopic total mesorectal excision after neoadjuvant chemoradiotherapy.
AB  - BACKGROUND: Although several authors have demonstrated that laparoscopic total
      mesorectal excision (TME) is feasible, safe, and has short-term benefits over
      open surgery, evidence about oncological outcome is lacking. Preoperative
      chemoradiation has been shown to improve local control in locally advanced rectal
      cancer. Therefore, neoadjuvant treatment followed by laparoscopic TME has become
      widely used. We reviewed our series of laparoscopic TME focusing on comparison
      between preoperative chemoradiation therapy and primary surgery. METHODS: Out of
      59 patients who underwent laparoscopic TME, 20 were submitted to neoadjuvant
      chemoradiation and represent study population. Twenty-six patients with non
      metastatic rectal cancer >T1 on pathologic TNM staging who underwent primary
      laparoscopic surgery were considered for comparison. RESULTS: No significant
      differences were found in operative time, in conversions to open surgery, in
      intra- and postoperative complications, and in anastomotic leakage rate between
      the two groups. No isolated local recurrence nor port-site metastases were
      detected in either group. Cumulative 3-year and 5-year survivals are also
      similar. CONCLUSION: Neoadjuvant treatment does not seem to jeopardize
      perioperative results of laparoscopic TME. The low incidence of local recurrence
      reported in both groups may be attributed to a more precise dissection allowed by
      the endoscopic view. Laparoscopic TME and preoperative chemoradiotherapy may
      significantly improve oncologic results and quality of life in patients with mid
      and low rectal cancer. Results should be validated by randomized trials with
      adequate follow-up.

PMID- 18042379
TI  - Selecting the optimum treatment for colorectal liver metastases.
AB  - There has been much improvement in the management of patients with colorectal
      liver metastases over the last 20 years. Appropriate selection of both treatment
      and patients can result in enhanced outcome. The main modalities of treatment are
      surgery, ablation, and combinations of chemotherapy drugs. Frequently, a
      combination of the above are required. This article summarises the most
      appropriate treatments designed to enhance outcome in these patients.

PMID- 18042380
TI  - New polyphenols active on beta-amyloid aggregation.
AB  - New polyphenol classes have been tested against amyloid-beta peptide aggregation.
      We have identified four novel polyphenols which could be efficient fibril
      inhibitors in Alzheimer's disease: malvidin and its glucoside and curculigosides
      B and D. We suggest that molecules with the particular C(6)-linkers-C(6)
      structure could be potent inhibitors. From the results reported for the flavan-3
      ol family, their anti-amyloidogenic effects against whole peptides (1-40 and 1
      42) could involve several binding sites.

PMID- 18042381
TI  - Amino acid derivatives as histone deacetylase inhibitors.
AB  - Ongoing clinical studies indicate that inhibitors of Class I and Class II histone
      deacetylase (HDAC) enzymes show great promise for the treatment of cancer.
      Zolinza (SAHA, Zolinza) was recently approved by the FDA for the treatment of the
      cutaneous manifestations of cutaneous T-cell lymphoma. As a part of an ongoing
      effort to identify novel small molecules to target these important enzymes, we
      have prepared several classes of amino acid-derived HDAC1 inhibitors. The design
      rationale and in vitro activity against the HDAC1 enzyme and HCT116 cell line are
      described in this letter.

PMID- 18042382
TI  - A very simple synthesis of GlcNAc-alpha-pyrophosphoryl-decanol: a substrate for
      the assay of a bacterial galactosyltransferase.
AB  - Lipid-linked sugar pyrophosphates, such as GlcNAc-pyrophosphoryl undecaprenol,
      are important intermediates in the biosynthesis of cell-surface bacterial
      polysaccharides. It was recently demonstrated that much simpler lipids could
      substitute for undecaprenol while retaining biological activity, thus making
      efficient synthetic access to this class of compounds highly desirable. In order
      to facilitate the synthesis of pure substrates for bacterial
      glycosyltransferases, we have developed a simple 'two-pot' synthesis which we
      demonstrate here for GlcNAc-alpha-pyrophosphoryl-decanol (4). GlcNAc
      pyrophosphate, produced by mild periodate oxidation/beta-elimination of
      commercial UDP-GlcNAc, is alkylated using 1-iododecane to yield the target
      compound 4 in 39% yield. Compound 4 is shown to be an efficient acceptor for a
      bacterial galactosyltransferase.

PMID- 18042383
TI  - Design and synthesis of a fluorescent muscarinic antagonist.
AB  - The design and concise synthesis of a fluorescent tolterodine-BODIPY (boron
      dipyrromethene) conjugate is described which possesses potent antimuscarinic
      activity. This derivative illustrates proof-of-concept for the preparation of
      other useful fluorophoric antimuscarinic agents which have potential utility in
      receptor occupancy studies and high throughput screens.

PMID- 18042384
TI  - Carbonic anhydrase inhibitors: copper(II) complexes of polyamino
      polycarboxylamido aromatic/heterocyclic sulfonamides are very potent inhibitors
      of the tumor-associated isoforms IX and XII.
AB  - Reaction of EDTA/DTPA dianhydride with aromatic/heterocyclic sulfonamides
      afforded a series of derivatives incorporating polyaminopolycarboxylate tails and
      benzenesulfonamide or 1,3,4-thiadiazole-2-sulfonamide heads. These compounds have
      been used as ligands to prepare Cu(II) complexes. Both parent sulfonamides as
      well as their copper complexes behaved as potent inhibitors of four carbonic
      anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, and transmembrane
      CA IX and XII. Some Cu(II) complexes showed subnanomolar affinities and some
      selectivity for the inhibition of the tumor-associated isoforms IX and XII and
      might be used as PET hypoxia markers of tumors.

PMID- 18042385
TI  - Spermicidal bacteriocins: lacticin 3147 and subtilosin A.
AB  - Spermicidal compounds that also exhibit antimicrobial properties would be
      extremely attractive agents as they could be used to not only prevent unwanted
      pregnancy but also to combat the growing prevalence of sexually transmitted
      infections (STI). One class of compounds that are potential candidates for
      development of dual-acting contraceptive products are antimicrobial peptides
      (AMPs). Herein, we report preliminary studies carried out to investigate the
      spermicidal activity of two bacteriocins, lacticin 3147 and subtilosin A, on
      bovine, horse/pony, boar and rat sperm.

PMID- 18042386
TI  - Time-to-progression in breast cancer: a stratification model for clinical trials.
AB  - The development of new anti-tumour drugs without clear cytoreductive activity has
      necessitated changes in the design of clinical trials. Defining the "time"
      parameter has become the essential objective of the majority of these trials.
      However, in breast cancer, this parameter is highly variable and, as such,
      difficult to quantify. We developed a useful tool that takes into account the
      inter-relatedness of all the variables known to have the capacity to predict the
      time-to-progression (TTP) in advanced breast cancer. From the Alamo database
      (GEICAM), we selected 1798 patients diagnosed as having metastatic breast cancer.
      Univariate analysis was performed using the method of Kaplan-Meier. Multivariate
      analysis was with the Cox regression method. The variables that were shown to
      have independent predictive value for the TTP were: non-visceral metastatic
      disease, single metastases, hormonal receptor positive N/T ratio<2 and disease
      free interval (DFI) > or = 24 months. Taking into account the variables that had
      reached an independent predictive value, we constructed a model of scoring in
      which the patients were grouped according to the TTP. Using our new scoring
      model, it is possible to group patients with metastatic breast cancer according
      to the predicted TTP. This can be a useful tool at the time of selecting and
      stratifying patients on entry into new randomised clinical trials.

PMID- 18042387
TI  - Cystic giant prolactinoma in childhood.
AB  - In childhood and adolescence, pituitary adenomas are rare and half are
      prolactinomas. However, cystic giant prolactinoma in prepuberty is extremely
      rare. In this report, we present a 10-year-old boy with a cystic giant
      prolactinoma who was treated with two-stage surgery as the tumor was dumbbell
      shaped. To our knowledge, this is the second reported case of a cystic giant
      prolactinoma in a prepubertal child.

PMID- 18042388
TI  - New 7,8-benzoflavanones as potent aromatase inhibitors: synthesis and biological
      evaluation.
AB  - Some natural compounds such as flavonoids are known to possess a moderate
      inhibitory activity against aromatase, this enzyme being an interesting target
      for hormone-dependent breast cancer treatment. It has been demonstrated that the
      modulation of flavonoid skeleton could increase anti-aromatase effect. Therefore,
      new 7,8-benzoflavanones were synthesized and tested for their activity toward
      aromatase inhibition. It was observed that the introduction of a benzo ring at
      position C-7 and C-8 on flavanone skeleton led to new potent aromatase
      inhibitors, the resulting 7,8-benzoflavanones being until nine times more potent
      than aminogluthetimide (the first aromatase inhibitor used clinically).

PMID- 18042389
TI  - N6-substituted C5'-modified adenosines as A1 adenosine receptor agonists.
AB  - Adenosines bearing 5'-modification in conjunction with an N6-substituent have
      previously been shown to act as partial agonists at the A1 adenosine receptor.
      Our current work investigates the effect of modifying the 5'-position in
      conjunction with efficacious bicyclic and tricyclic N6-substituents. Several
      highly potent agonists for the A1 adenosine receptor were identified; however,
      all of these compounds behaved as full agonists. In keeping with previous
      reports, 5'-halogen and 5'-sulfide derivatives of N6-(endo-norborn-2-yl)adenosine
      were, in general, low nanomolar agonists of the A1 adenosine receptor. The known
      partial agonist, N6-cyclopentyl-5'-deoxy-5'-ethylthioadenosine (2), also behaved
      as a full agonist in our assay.

PMID- 18042390
TI  - Comparison of the electronic structure of a thermoelectric skutterudite before
      and after adding rattlers: an electron energy loss study.
AB  - Skutterudites, with rattler atoms introduced in voids in the crystal unit cell,
      are promising thermoelectric materials. We modify the binary skutterudite with
      atomic content Co(8)P(24) in the cubic crystal unit cell by adding La as rattlers
      in all available voids and replacing Co by Fe to maintain charge balance,
      resulting in La(2)Fe(8)P(24). The intention is to leave the electronic structure
      unaltered while decreasing the thermal conductivity due to the presence of the
      rattlers. We compare the electronic structure of these two compounds by studying
      the L-edges of P and of the transition elements Co and Fe using electron energy
      loss spectroscopy (EELS). Our studies of the transition metal white lines show
      that the 3d electron count is similar for Co and Fe in these compounds. As
      elemental Fe has one electron less than Co, this supports the notion that each La
      atom donates three electrons. The L-edges of P in these two skutterudites are
      quite similar, signalling only minor differences in electronic structure. This is
      in reasonable agreement with density functional theory (DFT) calculations, and
      with our multiple scattering FEFF calculations of the near edge structure.
      However, our experimental plasmon energies and dielectric functions deviate
      considerably from predictions based on DFT calculations.

PMID- 18042391
TI  - Description and interpretation of the bracts epidermis of Gramineae (Poaceae)
      with rotated image with maximum average power spectrum (RIMAPS) technique.
AB  - During the last few years, RIMAPS technique has been used to characterize the
      micro-relief of metallic surfaces and recently also applied to biological
      surfaces. RIMAPS is an image analysis technique which uses the rotation of an
      image and calculates its average power spectrum. Here, it is presented as a tool
      for describing the morphology of the trichodium net found in some grasses, which
      is developed on the epidermal cells of the lemma. Three different species of
      grasses (herbarium samples) are analyzed: Podagrostis aequivalvis (Trin.) Scribn.
      & Merr., Bromidium hygrometricum (Nees) Nees & Meyen and Bromidium ramboi
      (Parodi) Rugolo. Simple schemes representing the real microstructure of the lemma
      are proposed and studied. RIMAPS spectra of both the schemes and the real
      microstructures are compared. These results allow inferring how similar the
      proposed geometrical schemes are to the real microstructures. Each geometrical
      pattern could be used as a reference for classifying other species. Finally, this
      kind of analysis is used to determine the morphology of the trichodium net of
      Agrostis breviculmis Hitchc. As the dried sample had shrunk and the
      microstructure was not clear, two kinds of morphology are proposed for the
      trichodium net of Agrostis L., one elliptical and the other rectilinear, the
      former being the most suitable.

PMID- 18042392
TI  - Nicotinate riboside salvage in plants: presence of nicotinate riboside kinase in
      mungbean seedlings.
AB  - Salvage of nicotinate riboside for NAD synthesis was investigated in mungbean
      seedlings. Nicotinate riboside kinase activity was detected in extracts from
      cotyledons. Exogenously supplied [carboxyl-(14)C]nicotinate riboside was readily
      converted into pyridine nucleotides in cotyledons of mungbean seedlings. This
      conversion was also found in embryonic axes, but the rate was lower than in
      cotyledons. These results suggest that, in addition to the seven-component
      pyridine nucleotide cycle (PNC VII), an eight-component cycle (PNC VIII)
      involving nicotinate riboside kinase operates in plants.

PMID- 18042393
TI  - Transpiration, CO2 assimilation, WUE, and stomatal aperture in leaves of Viscum
      album (L.): Effect of abscisic acid (ABA) in the xylem sap of its host (Populus x
      euamericana).
AB  - Leaves of the mistletoe Viscum album (L.) show a high rate of transpiration, even
      when the host is under severe drought stress. The hypothesis that a strong
      control of ABA influx from the xylem sap of the host into the mistletoe prevents
      stomatal closure in mistletoe leaves was tested under the following conditions:
      sections of poplar twigs carrying a mistletoe were perfused with artificial xylem
      sap that contained different ABA concentrations and both transpiration and ABA
      levels were analysed in mistletoe leaves. Despite variation by a factor of 10(4),
      the ABA content of the host xylem did not affect ABA levels, leaf transpiration,
      CO(2) assimilation, WUE, or the degree of stomatal aperture in mistletoe leaves.
      These observations support the hypothesis of a strong control of ABA influx from
      the host of the xylem into the mistletoe, although degradation of ABA before it
      enters the mistletoe leaves cannot be excluded. This mechanism may ensure a water
      and nutritional status favourable for the mistletoe, even if the water status of
      the host is impaired. Despite the lack of short-term sensitivity of ABA levels in
      mistletoe leaves to even strong changes of ABA levels in the xylem sap of the
      host, ABA levels in mistletoe leaves were relatively high compared to ABA levels
      in the leaves of several tree species including poplar. Since significant
      transpiration of the mistletoe leaves was observed despite high ABA levels, a
      diminished sensitivity of the stomata of mistletoe leaves to ABA has to be
      concluded. The stomatal density of adaxial Viscum leaves of 89+/-23 stomata per
      mm is lower than those reported in a study performed at the end of the 19th
      century.

PMID- 18042395
TI  - Adenosine instead of supranormal potassium in cardioplegic solution preserves
      endothelium-derived hyperpolarization factor-dependent vasodilation.
AB  - OBJECTIVE: We have recently shown that adenosine instead of supranormal potassium
      in cold crystalloid cardioplegia improves cardioprotection. Studies indicate that
      hyperkalemia has unfavorable effects on vascular endothelial function. Three
      pathways have been identified as major vasodilatory pathways: the nitric oxide
      (NO) pathway, the cyclooxygenase (COX) pathway, and the endothelium-derived
      hyperpolarization (EDHF) pathway, where the EDHF pathway, in particular, seems
      susceptible to hyperkalemia. We hypothesized that adenosine cardioplegia improves
      postcardioplegic endothelial function. METHODS: Sixteen pigs were randomized to
      receive either cold (6 degrees C) hyperkalemic cardioplegia (n=8) or cardioplegia
      where hyperkalemia was substituted with 1.2 mM adenosine (n=8). After 1h of cold
      ischemic arrest, coronary blood flow was monitored for the following 2h. The LAD
      artery was then explanted, and cylindrical rings were mounted for isometric
      tension recordings in organ chambers. Vessels were preconstricted with U46610
      (Thromboxane A(2) analog) and then bradykinin-mediated relaxation was
      investigated. To differentiate between the vasodilatory pathways the relaxation
      was assessed in the absence and presence of inhibitors of the COX (indomethacin),
      NO (L-NAME+carboxy-PTIO), and EDHF (apamin+charybdotoxin) pathways. RESULTS:
      Invivo: The adenosine group had, as distinct from the hyperkalemic group, a
      significantly increased coronary blood flow index 1h after cross-clamp release
      (from (ml/min/100 g, mean+/-SD) 50.9+/-13.9 to 72.8+/-21.9, p=0.010). The
      difference was, however, not statistically significant between groups. Invitro:
      Maximal relaxation without blockers was 27.4+/-10.1% of maximal tension in the
      adenosine group and 22.2+/-7.5% in the hyperkalemic group. To investigate EDHF
      dependent vasodilation the vessel rings were simultaneously treated with
      indomethacin, L-NAME, and carboxy-PTIO. Maximal relaxation in the hyperkalemic
      group was then reduced to 47.4+/-17.4% of maximal tension, which was a
      significant reduction compared to the adenosine group with a maximal relaxation
      of 20.6+/-8.7% (p=0.028). CONCLUSION: Adenosine instead of supranormal potassium
      in cold crystalloid cardioplegia increases postcardioplegic myocardial blood flow
      and preserves EDHF-dependent vasodilation.

PMID- 18042394
TI  - The drought response of Theobroma cacao (cacao) and the regulation of genes
      involved in polyamine biosynthesis by drought and other stresses.
AB  - Drought can negatively impact pod production despite the fact that cacao
      production usually occurs in tropical areas having high rainfall. Polyamines
      (PAs) have been associated with the response of plants to drought in addition to
      their roles in responses to many other stresses. The constitutive and drought
      inducible expression patterns of genes encoding enzymes involved in PA
      biosynthesis were determined: an ornithine decarboxylase (TcODC), an arginine
      decarboxylase (TcADC), an S-adenosylmethionine decarboxylase (TcSAMDC), a
      spermidine synthase (TcSPDS), and a spermine synthase (TcSPMS). Expression
      analysis using quantitative real-time reverse transcription-PCR (QPCR) results
      showed that the PA biosynthesis genes were expressed in all plant tissues
      examined. Constitutive expression of PA biosynthesis genes was generally highest
      in mature leaves and open flowers. Expression of TcODC, TcADC, and TcSAMDC was
      induced with the onset of drought and correlated with changes in stomatal
      conductance, photosynthesis, photosystem II efficiency, leaf water potential and
      altered emission of blue-green fluorescence from cacao leaves. Induction of
      TcSAMDC in leaves was most closely correlated with changes in water potential.
      The earliest measured responses to drought were enhanced expression of TcADC and
      TcSAMDC in roots along with decreases in stomatal conductance, photosynthesis,
      and photosystem II efficiency. Elevated levels of putrescine, spermidine, and
      spermine were detected in cacao leaves 13days after the onset of drought.
      Expression of all five PA associated transcripts was enhanced (1.5-3-fold) in
      response to treatment with abscisic acid. TcODC and TcADC, were also responsive
      to mechanical wounding, infection by Phytophthora megakarya (a causal agent of
      black pod disease in cacao), the necrosis- and ethylene-inducing protein (Nep1)
      of Fusarium oxysporum, and flower abscission. TcSAMDC expression was responsive
      to all stresses except flower abscission. TcODC, although constitutively
      expressed at much lower levels than TcADC, TcSAMDC, TcSPDS, and TcSPMS, was
      highly inducible by the fungal protein Nep1 (135-fold) and the cacao pathogen
      Phytophthora megakarya (671-fold). The full length cDNA for ODC was cloned and
      characterized. Among the genes studied, TcODC, TcADC, and TcSAMDC were most
      sensitive to induction by drought in addition to other abiotic and biotic
      stresses. TcODC, TcADC, and TcSAMDC may share signal transduction pathways and/or
      the stress induced signal induction pathways may converge at these three genes
      leading to similar although not identical patterns of expression. It is possible
      altering PA levels in cacao will result in enhanced tolerance to multiple
      stresses including drought and disease as has been demonstrated in other crops.

PMID- 18042396
TI  - Large thrombus on a cardiac defibrillator lead.

PMID- 18042397
TI  - Labrafil--a new adjuvant for peptide-specific oral tolerance in rat experimental
      autoimmune uveitis.
AB  - Application of soluble antigen via the oral route results in systemic antigen
      specific tolerance, a therapeutic approach that has already been used for uveitis
      patients. In the Lewis rat experimental autoimmune uveitis (EAU) can be induced
      by active immunisation with retinal antigens such as retinal soluble antigen (S
      Ag) or interphotoreceptor retinoid-binding protein (IRBP) and peptides thereof.
      These normally pathogenic antigens can also be used to induce oral tolerance. In
      order to optimize oral tolerance induction we analysed the effect of Labrafil M
      2125 CS, an orally administrable composition for pharmaceutical use, consisting
      of fatty acid esters and glycerides and capable of forming micro emulsions.
      Feeding peptide emulsified in Labrafil M 2125 CS/PBS prior to immunisation
      significantly improved oral tolerance compared to feeding peptide in PBS only. We
      observed a delayed onset of disease, reduced intraocular inflammation and less
      retinal destruction. Application of Labrafil M 2125 CS without tolerogen had no
      effect. Combined feeding of peptide with Labrafil M 2125 CS even allowed 10-fold
      reduction of the tolerogenic peptide dose. Furthermore, the effect of Labrafil M
      2125 CS upon oral tolerance was dose-dependent, a peptide emulsion containing 0.5
      2% Labrafil M 2125 CS achieved a maximal enhancement of oral tolerance induction,
      suggesting that Labrafil M 2125 CS might be a useful adjuvant to enhance
      therapeutic use of oral tolerance.

PMID- 18042398
TI  - Plasminogen activator induction facilitates recovery of respiratory function
      following spinal cord injury.
AB  - The possibility that plasminogen activator (PA) plays a role in synaptic
      plasticity was explored in the spinal cord during the crossed phrenic phenomenon
      (CPP), where respiratory functional plasticity develops following spinal cord
      injury. Synaptic remodeling on phrenic motorneurons occurs during the
      characteristic delay period following spinal cord injury before CPP recovery of
      respiratory function. The molecular mechanisms underlying this plasticity are not
      well-defined. During the critical 1-2 h delay period required for this synaptic
      plasticity following a C2 hemisection in mice, uPA and tPA mRNAs are rapidly
      induced in C4-5 ventral spinal cord neurons in the ipsilateral phrenic motor
      nucleus (PMN), as are uPA and tPA protein levels. A role for uPA in CPP spinal
      cord plasticity is confirmed by the impaired ability of uPA knockout mice to
      acquire a good CPP response by 6 h post-hemisection and their lack of structural
      remodeling of PMN synapses that underlies development of the CPP response.

PMID- 18042399
TI  - Rapid and sensitive anthrone-sulfuric acid assay in microplate format to quantify
      carbohydrate in biopharmaceutical products: method development and validation.
AB  - The need for an accurate, fast and reliable analysis of carbohydrate test is
      crucial for numerous biological processes. In that sense, anthrone-sulfuric acid
      assay is one of the most efficient quantification techniques successfully applied
      to carbohydrate determination. In this paper, a sensitive and accurate anthrone
      sulfuric acid microplate assay was developed and validated for the quantitative
      estimation of yeast carbohydrates in the production of hepatitis B virus surface
      antigen, and the main component of the recombinant vaccine HEBERBIOVAC HB. A
      response surface methodology was applied to design and optimize the assay in
      order to maximize the differences on the expected effect and to minimize the
      number of experiments. The proposed method was linear over the concentration
      range from 10 to 120 microg/mL for glucose, with values for the coefficient of
      determination >0.99. Intra- and inter-assay variation coefficient ranged between
      0.45-4.79% and 2.48-8.94%, respectively. The Student t-test used in the
      interference study, revealed good parallelism among curves (T(obs)< or =T(0.05)),
      which indicates the lack of interference in the working range. Yields obtained in
      accuracy test for two concentration levels varied between 90 and 105%, confirming
      the assay's reliability. In conclusion, the validated method, which has
      successfully been used for the process control monitoring of several samples
      generated from the production of hepatitis B vaccine, allows the quality and
      purity of the final product.

PMID- 18042400
TI  - Regulated expression of active biotinylated G-protein coupled receptors in
      mammalian cells.
AB  - We have developed a mammalian expression system suitable for the production of
      enzymatically biotinylated integral membrane proteins. The key feature of this
      system is the doxycycline (dox)-regulated co-expression of a secreted variant of
      Escherichia coli biotin ligase (BirA) and a target protein with a 13-residue
      biotin acceptor peptide (BioTag) appended to its extracellular domain. Here we
      describe the expression and functional analysis of three G-protein coupled
      receptors (GPCRs): protease-activated receptors (PARs) 1 and 2, and the platelet
      ADP receptor, P2Y(12). Clonal Chinese hamster ovary (CHO) Tet-On cell lines that
      express biotinylated GPCRs were rapidly isolated by fluorescence-activated cell
      sorting following streptavidin-FITC staining, thereby circumventing the need for
      manual colony picking. Analysis by Western blotting with streptavidin-HRP
      following endoglycosidase treatment revealed that all three GPCRs undergo N
      linked glycosylation. The expression of biotinylated GPCRs on the cell surface
      was regulated by the concentration of dox in the medium, reaching a maximum at
      approximately 1 microg/mL dox. Similarly, the extent of GPCR biotinylation was
      dependent on biotin concentration, with maximum and complete biotinylation
      achieved upon supplementation with 50 microM biotin. Biotinylated PAR1 and PAR2
      were readily and specifically cleaved on the surface of intact cells by their
      cognate proteases, and were capable of transducing extracellular stimuli,
      resulting in the downstream phosphorylation of extracellular signal-regulated
      kinase (ERK) 1/2. Notably, P2Y(12) mediated agonist-induced ERK phosphorylation
      only when it was expressed at low levels on the cell surface, highlighting the
      utility of regulated expression for the production of functionally active GPCRs
      in mammalian cells.

PMID- 18042401
TI  - Neurobiological regret and rejoice functions for aversive outcomes.
AB  - A decision maker may experience regret when a choice he makes results in a more
      adverse outcome than a different choice would have yielded. Analogously, he may
      experience rejoice when his choice resulted in better outcomes. We used fMRI to
      investigate the neural correlates of regret and rejoice where payoffs are in
      terms of a non-monetary medium. Incentives were created using painful outcomes in
      the form of mild electrical shocks to the foot and the possibility of avoiding
      them. We hypothesized that the neural response to a painful outcome resulting
      from an individual's choice would also reflect the degree of regret as measured
      by the likelihood that alternative choices would have yielded the same adverse
      outcome. Similarly, when an individual avoids a potential shock, he would
      experience a degree of rejoice that correlates with the probability he had of
      receiving the shock. For example, winning a bet when winning was unlikely, even
      if the outcome is the same, evokes more rejoice than winning when it was highly
      probable. Our results suggest that activation of a cortical network, consisting
      of the medial orbitofrontal cortex, left superior frontal cortex, right angular
      gyrus, and left thalamus, correlates with the degree of regret. A different
      network, including the rostral anterior cingulate, left hippocampus, left ventral
      striatum, and brain stem/midbrain correlated with rejoice. The right inferior
      orbitofrontal cortex, pre-supplementary motor area, anterior cingulate, and
      posterior cingulate showed similar patterns of activation with both regret and
      rejoice, suggesting that these regions may be associated with surprise from the
      realization of relatively unlikely events. Our results suggest that distinct, but
      overlapping networks are involved in the experiences of regret and rejoice.

PMID- 18042402
TI  - Effect of anatomical variability, reconstruction algorithms and scattered photons
      on the SPM output of brain PET studies.
AB  - Statistical parametric mapping (SPM) has become the standard technique to
      statistically evaluate differences between functional images. The aim of this
      paper was to assess the effect of anatomical variability of skull, the
      reconstruction algorithm and the scattering of photons in the brain on the output
      of an SPM analysis of brain PET studies. To this end, Monte Carlo simulation was
      used to generate suitable PET sinograms and bootstrap techniques were employed to
      increase the reliability of the conclusions. Activity distribution maps were
      obtained by segmenting thirty nine T1-weighted magnetic resonance images. Foci
      were placed on the posterior cingulate cortex (PCC) and the superior temporal
      cortex (STC) and activation factors ranging between -25% and +25% were simulated.
      Preprocessing of the reconstructed images and statistical analysis were performed
      using SPM2. Our findings show that intersubject anatomical differences can cause
      the minimum sample size to increase between 10 and 42% for posterior cingulate
      Cortex and between 40 and 80% for superior temporal cortex. Ideal scatter
      correction (ISC) allowed us to diminish the sample size up to 18% and fully 3D
      reconstruction reduced the minimum sample size between 8 and 33%. Detection
      sensitivity was higher for hypo-activation than for hyper-activation situations
      and higher for superior temporal cortex than for posterior cingulate cortex.

PMID- 18042403
TI  - Evolutionary relationships within the Neotropical, eusporangiate fern genus
      Danaea (Marattiaceae).
AB  - Genera within the eusporangiate fern family Marattiaceae have long been neglected
      in taxonomic and systematic studies. Here we present the first phylogenetic
      hypothesis of relationships within the exclusively Neotropical genus Danaea based
      on a sampling of 60 specimens representing 31 species from various Neotropical
      sites. We used DNA sequence data from three plastid regions (atpB, rbcL, and trnL
      F), morphological characters from both herbarium specimens and live plants
      observed in the field, and geographical and ecological information to examine
      evolutionary patterns. Eleven representatives of five other marattioid genera
      (Angiopteris, Archangiopteris, Christensenia, Macroglossum, and Marattia) were
      used to root the topology. We identified three well-supported clades within
      Danaea that are consistent with morphological characters: the "leprieurii" clade
      (containing species traditionally associated with the name D. elliptica), the
      "nodosa" clade (containing all species traditionally associated with the name D.
      nodosa), and the "alata" clade (containing all other species). All three clades
      are geographically and ecologically widely distributed, but subclades within them
      show various distribution patterns. Our phylogenetic hypothesis provides a robust
      framework within which broad questions related to the morphology, taxonomy,
      biogeography, evolution, and ecology of these ferns can be addressed.

PMID- 18042404
TI  - The complete mitochondrial genomes of needle corals, Seriatopora spp.
      (Scleractinia: Pocilloporidae): an idiosyncratic atp8, duplicated trnW gene, and
      hypervariable regions used to determine species phylogenies and recently diverged
      populations.
AB  - Complete DNA sequences were determined for the mitochondrial (mt) genomes of the
      needle corals, Seriatopora caliendrum (17,011bp) and S. hystrix (17,060bp). Gene
      arrangement of the Seriatopora mt genomes is similar to the 14 currently
      published scleractinian mitogenomes with three unusual features, including an
      idiosyncratic atp8, a duplicated trnW (tRNA(TRP)), and a putative control region
      located between atp6 and nad4. Atp8, located between duplicate trnW genes, showed
      relatively low amino acid similarity (25.6-34.6%) with those of published
      scleractinian corals. A reverse-transcription polymerase chain reaction confirmed
      the transcription of this novel atp8 gene in Seriatopora. A duplicated trnW was
      detected in the region close to the cox1 gene and shares the highly conserved
      primary and secondary structure of its original counterpart. The intergenic
      spacer between atp6 and nad4, which contains several distinct repeated elements,
      is being designated as the putative control region in the Seriatopora mt genomes.
      Evaluation of the molecular evolution of several protein-coding genes and
      intergenic spacers showed 3- to 4-fold higher divergence rates among populations
      or between species than those published for scleractinian mt genomes. This study
      not only successfully revealed the phylogenies of S. hystrix and S. caliendrum
      from the West Pacific Ocean by mtDNA, but also highlighted the potential
      utilities of mt hypervariable regions in phylogenetic construction below the
      species level for Seriatopora.

PMID- 18042405
TI  - Higher level phylogeny and evolutionary trends in Campanulaceae subfam.
      Lobelioideae: molecular signal overshadows morphology.
AB  - Relationships within the subfamily Lobelioideae in Campanulaceae are inferred
      from DNA sequence variation in the rbcL and ndhF genes, and the trnL-F region
      including the trnL intron and the trnL-F intergenic spacer. Results derived from
      Bayesian and parsimony analyses provide evidence for the long-suspected paraphyly
      of the genus Lobelia, comprising over 400 species as presently circumscribed. The
      perennial dwarf herbs belonging to the Andean genus Lysipomia are sister to a
      group comprising the Neotropical shrubs Burmeistera, Centropogon, and
      Siphocampylus. Giant lobelioids from the Hawaiian Islands, Brazil, Africa, and
      Sri Lanka form a strongly supported group. Character optimizations on the
      phylogenetic tree reveal that shifts in fruit types and lignification have
      occurred much more commonly than generally assumed. The main clades in the
      subfamily are outlined, which largely contradict previous classifications based
      on morphology.

PMID- 18042406
TI  - Phylogenetic relationships of tyrant-flycatchers (Aves: Tyrannidae), with an
      emphasis on the elaeniine assemblage.
AB  - The tyrant-flycatchers (Tyrannidae) are arguably the largest avian family in the
      Western Hemisphere with approximately 100 genera and 430 species. Although the
      composition of the family is largely settled, intergeneric relationships are
      poorly understood. Morphological and behavior-based classifications are in
      disagreement with DNA-DNA hybridization data, and both have recently been
      contradicted by DNA-sequence studies. However, previous DNA-sequence sampling has
      mostly focused on two out of the six traditional tribes. In this study, we have
      sampled mitochondrial and nuclear sequences of additional tyrannid genera from
      across the Tyrannidae, with particularly dense coverage of a third tribe
      (Elaeniini). Our data corroborate previous DNA-sequence studies that demonstrate
      a basal division of Tyrannidae into a pipromorphine group (recruited from two
      morphological tribes) and the core Tyrannidae. Furthermore, we identify a new
      assemblage that includes Platyrinchus and the enigmatic Neopipo, although the
      position of this lineage within the Tyrannidae remains incertae sedis. Within the
      core Tyrannidae, we find strong support for a monophyletic elaeniine assemblage,
      and discuss a number of strongly supported sub-clades and species-level
      arrangements that display varying levels of agreement with previous
      classifications. The elaeniine assemblage may be the sister group to all other
      core Tyrannidae, and it is in virtually complete congruence with a previous
      classificatory scheme based on syringeal morphology.

PMID- 18042407
TI  - The phylogenetic problem of Huia (Amphibia: Ranidae).
AB  - A taxonomic consensus for the diverse and pan-global frog family Ranidae is
      lacking. A recently proposed classification of living amphibians [Frost, D.R.,
      Grant, T., Faivovich, J., Bain, R. H., Haas, A., Haddad, C.F.B., de Sa, R.O.,
      Channing, A., Wilkinson, M., Donnellan, S.C., Raxworthy, C.J., Campbell, J.A.,
      Blotto, B.L., Moler, P., Drewes, R.C., Nussbaum, R.A., Lynch, J.D., Green, D.M.,
      Wheeler, W.C., 2006. The amphibian tree of life. B. Am. Mus. Nat. Hist. 297, 1
      370] included expansion of the Southeast Asian ranid frog genus Huia from seven
      to 47 species, but without having studied the type species of Huia. This study
      tested the monophyly of this concept of Huia by sampling the type species and
      putative members of Huia. Molecular phylogenetic analyses consistently recovered
      the type species H. cavitympanum as the sister taxon to other Bornean-endemic
      species in the genus Meristogenys, rendering all previously published concepts of
      Huia as polyphyletic. Members of Huia sensu [Frost, D.R., Grant, T., Faivovich,
      J., Bain, R. H., Haas, A., Haddad, C.F.B., de Sa, R.O., Channing, A., Wilkinson,
      M., Donnellan, S.C., Raxworthy, C.J., Campbell, J.A., Blotto, B.L., Moler, P.,
      Drewes, R.C., Nussbaum, R.A., Lynch, J.D., Green, D.M., Wheeler, W.C., 2006. The
      amphibian tree of life. B. Am. Mus. Nat. Hist. 297, 1-370.] appear in four places
      within the family Ranidae. A clade containing the type species of Odorrana is
      phylogenetically unrelated to the type species of Huia, and Odorrana is removed
      from synonymy with Huia. These findings underscore the need to include relevant
      type species in phylogenetic studies before proposing sweeping taxonomic changes.
      The molecular phylogenetic analyses revealed a high degree of homoplasy in larval
      and adult morphology of Asian ranid frogs. Detailed studies are needed to
      identify morphological synapomorphies that unite members in these major clades of
      ranid frogs.

PMID- 18042408
TI  - Divergence dates of libelluloid dragonflies (Odonata: Anisoptera) estimated from
      rRNA using paired-site substitution models.

PMID- 18042409
TI  - Evaluation of autologous chondrocyte transplantation via a collagen membrane in
      equine articular defects: results at 12 and 18 months.
AB  - OBJECTIVE: To evaluate a technique of autologous chondrocyte implantation (ACI)
      similar to the other techniques using cell-seeded resorbable collagen membranes
      in large articular defects. METHODS: Autologous cartilage was harvested
      arthroscopically from the lateral trochlear ridge of the femur in fifteen 3-year
      old horses. After culture and expansion of chondrocytes the newly created ACI
      construct (autologous chondrocytes cultured expanded, seeded on a collagen
      membrane, porcine small intestine submucosa) was implanted into 15mm defects on
      the medial trochlear ridge of the femur in the opposite femoropatellar joint.
      Using two defects in each horse, the ACI technique was compared to collagen
      membrane alone (CMA) and empty cartilage defects (ECDs). RESULTS: Arthroscopic
      evaluations at 4, 8, 12 and 18 months demonstrated that CMA was significantly
      worse compared to ACI or ECD treatments, with ACI having the best overall
      subjective grade. Overall raw histological scores demonstrated a significant
      improvement with ACI compared to either CMA or ECD treated defects and ACI
      defects had significantly more immunohistochemical staining for aggrecan than CMA
      or ECD treated defects (with significantly more type II collagen in ACI and ECD
      compared to CMA defects) at 12 and 18 months. CONCLUSIONS: Histologic and
      immunohistochemistry results from this long-term randomized study are
      particularly encouraging and demonstrate superiority with the ACI technique.
      Although there is no comparable study published with the traditional ACI
      technique in the horse (or with such a large defect size in another animal
      model), the use of a solid autologous cell-seeded-constructed implant would
      appear to offer considerable clinical advantages.

PMID- 18042410
TI  - Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis
      (OA) patients: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To evaluate the efficacy of preparations with avocado-soybean
      unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on
      randomized controlled trials (RCTs). METHOD: RCTs from systematic searches were
      included if they explicitly stated that hip and/or knee OA patients were
      randomized to either ASU or placebo. The co-primary outcome was reduction in pain
      and Lequesne index, leading to effect size (ES), calculated as the standardized
      mean difference. As secondary analysis, the number of responders to therapy was
      analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied
      for the meta-analyses, using mixed effects models. RESULTS: Four trials--all
      supported by the manufacturer--were included, with 664 OA patients with either
      hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo
      (328). Average trial duration was 6 months (range: 3-12 months). Though based on
      heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES
      = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne
      index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003).
      Secondarily, the number of responders following ASU compared to placebo (OR =
      2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients.
      CONCLUSIONS: Based on the available evidence, patients may be recommended to give
      ASU a chance for e.g., 3 months. Meta-analysis data support better chances of
      success in patients with knee OA than in those with hip OA.

PMID- 18042411
TI  - Prebiotic effectiveness of inulin extracted from edible burdock.
AB  - To investigate the prebiotic potential of burdock inulin (B-INU), the in vitro
      and in vivo effects of B-INU on bacterial growth were studied. B-INU
      significantly stimulated the growth of bifidobacteria in Man-Rogosa-Sharp (MRS)
      medium, anaerobically. Compared with chicory inulin (C-INU), long-chain inulin (L
      INU) and fructooligosaccharides (FOS), 1% (w/v) B-INU promoted the specific
      growth rate of beneficial bacteria. The decreases of media pH with B-INU were
      almost the same as that with C-INU and FOS. In vivo, B-INU significantly
      increased the number of lactobacilli and bifidobacteria (P<0.05) in cecal
      content. Mice fed with B-INU, C-INU and FOS for 14 days had greater number of
      cecal beneficial bacteria population than those fed with L-INU for 14 days. In
      addition, all fructans did not cause any side effects, such as eructation and
      bloating. Results indicated that inulin extracted from edible burdock showed
      prebiotic properties that could promote health.

PMID- 18042412
TI  - A novel (Leu183Pro-)mutation in the HFE-gene co-inherited with the Cys282Tyr
      mutation in two unrelated Dutch hemochromatosis patients.
AB  - We describe a novel heterozygous mutation in exon 3 of the HFE-gene that was co
      inherited with Cys282Tyr in two unrelated Dutch men both presenting a classical
      form of hereditary hemochromatosis. Heterozygosity for this mutation was also
      found in one out of 100 healthy controls of Dutch descent. This c.548T>C mutation
      converts a leucine to a proline residue at position 183 in the alpha2-helix of
      the HFE-protein (Leu183Pro). Standard bioinformatics analysis shows that the
      mutation is likely to disturb the HFE interaction with TfR1. This disrupting role
      of the mutation in the iron regulatory pathway is further corroborated by the
      familial co-occurrence of the observed compound heterozygosity with increased
      serum iron parameters. Haplotype analysis strongly suggests that this novel
      mutation arose from a common ancestor in the distant past. These findings may
      have implications for HFE-testing of iron overloaded heterozygous Cys282Tyr
      patients of Northern European origin and their relatives.

PMID- 18042413
TI  - Millimetre wave therapy for pain relief after total knee arthroplasty: a
      randomised controlled trial.
AB  - Millimetre wave therapy (MWT) is a promising complementary method for pain
      relief, however rigorous investigations of its effectiveness are needed. The
      purpose of this study was to examine if MWT can reduce opioid requirement
      compared to sham procedure applied for relief of acute pain in patients after
      total knee arthroplasty (TKA). Eighty patients undergoing TKA were randomly
      assigned to receive MWT or sham procedure. Patients and evaluators were blinded
      to the group allocation. MWT consisted of six sessions, each session of 30 min
      duration. During each session the knee wound was exposed to electromagnetic waves
      with frequency 50-75 GHz and power density 4.2 mW/cm(2). Postoperative analgesia
      with piritramide, a weak opioid with 0.7 potency of morphine delivered via
      patient-controlled analgesia pump, was directed to achieve pain intensity of less
      than 40 on a 100 mm visual analogue scale (VAS). The primary outcome measure was
      postoperative piritramide requirement for three days after surgery. Secondary
      outcome measures were: total ibuprofen requirement from the fourth postoperative
      day to discharge; success of patients' blinding; patients' satisfaction with pain
      relief; incidence of analgesia-related side effects; heart rate and blood
      pressure. Piritramide requirement was similar in both groups whereby all patients
      reported adequate pain relief measured on a VAS. Secondary outcome measures were
      also comparable in both groups. The majority of patients in both groups believed
      they had received true MWT and wanted to repeat it in future. Millimetre waves
      applied to surfaces of surgical wounds did not reduce opioid requirement compared
      to the sham procedure after TKA.

PMID- 18042415
TI  - Polarity dependence of EPR parameters for TOAC and MTSSL spin labels: correlation
      with DOXYL spin labels for membrane studies.
AB  - TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) is a
      nitroxyl amino acid that can be incorporated in the backbone of peptides. DOXYL
      (4,4-dimethyl-oxazolidine-1-oxyl) is a nitroxyl ring that can be attached rigidly
      at specific C-atom positions in the acyl chains of phospholipids. Spin-labelled
      phosphatidylcholines of the DOXYL type have been used previously to establish the
      transmembrane polarity profile in biological lipid bilayers [D. Marsh, Polarity
      and permeation profiles in lipid membranes, Proc. Natl. Acad. Sci. USA 87 (2001)
      7777-7782]. Here, we determine the polarity dependence of the isotropic (14)N
      hyperfine couplings, a(o)(N), and g-values, g(o), in a wide range of protic and
      aprotic media, for a TOAC-containing dipeptide (Fmoc-TOAC-Aib-OMe) and for a
      DOXYL-containing fatty acid (12-DOXYL-stearic acid). The correlation between
      datasets for TOAC and DOXYL nitroxides in the various solvents is used to
      establish the polarity profile for isotropic hyperfine couplings of TOAC in a
      transmembrane peptide. This calibration can be used to determine the location of
      TOAC at selected residue positions in a transmembrane or surface-active peptide.
      A similar calibration procedure is also applied to a(o)(N) and g(o) for the
      pyrroline methanethiosulphonate nitroxide (MTSSL) that is used in site-directed
      spin-labelling studies of membrane proteins.

PMID- 18042414
TI  - Evaluation of sub-microsecond recovery resonators for in vivo electron
      paramagnetic resonance imaging.
AB  - Time-domain (TD) electron paramagnetic resonance (EPR) imaging at 300MHz for in
      vivo applications requires resonators with recovery times less than 1 micros
      after pulsed excitation to reliably capture the rapidly decaying free induction
      decay (FID). In this study, we tested the suitability of the Litz foil coil
      resonator (LCR), commonly used in MRI, for in vivo EPR/EPRI applications in the
      TD mode and compared with parallel coil resonator (PCR). In TD mode, the
      sensitivity of LCR was lower than that of the PCR. However, in continuous wave
      (CW) mode, the LCR showed better sensitivity. The RF homogeneity was similar in
      both the resonators. The axis of the RF magnetic field is transverse to the
      cylindrical axis of the LCR, making the resonator and the magnet co-axial.
      Therefore, the loading of animals, and placing of the anesthesia nose cone and
      temperature monitors was more convenient in the LCR compared to the PCR whose
      axis is perpendicular to the magnet axis.

PMID- 18042416
TI  - Feline heartworm disease: a clinical review.
AB  - Feline heartworm disease is caused by the filarial nematode Dirofilaria immitis,
      and is transmitted by mosquitoes in heartworm-endemic areas worldwide. While dogs
      are the definitive hosts for this parasite, cats can also be infected, and the
      overall prevalence in cats is between 5% and 10% of that in dogs in any given
      area. The spectrum of feline presentations varies from asymptomatic infections to
      chronic respiratory signs, sometimes accompanied by chronic vomiting to acute
      death with no premonitory signs. Ante-mortem diagnosis can be challenging and
      relies on a combination of tests, including antigen and antibody serology,
      thoracic radiography and echocardiography. As treatment with heartworm
      adulticidal drugs can be life-threatening and heartworm infection in cats is
      often self-limiting, infected cats are frequently managed with supportive
      treatment (corticosteroids, bronchodilators, and anti-emetics). Surgical removal
      of filariae using extraction devices may be considered in some acute cases where
      immediate curative treatment is necessary, but filarial breakage during the
      procedure may result in an acute fatal shock-like reaction. Necropsy findings are
      mainly pulmonary and include muscular hypertrophy of the pulmonary arteries and
      arterioles on histopathology. A number of safe and effective macrocytic lactone
      drugs are available for prophylaxis in cats. These drugs can kill a range of
      larval and adult life-cycle stage heartworms, which may be advantageous in cases
      of owner compliance failure or when heartworm infection status is undetermined at
      the time prophylaxis is commenced. An index of suspicion for feline heartworm
      disease is warranted in unprotected cats with respiratory signs, and perhaps
      chronic vomiting, in areas where canine heartworm disease is endemic. Many cats,
      once diagnosed and with appropriate supportive care and monitoring, will resolve
      their infection and be free of clinical signs.

PMID- 18042418
TI  - [Recurrence of stress urinary incontinence after tension-free vaginal tape and
      childbirth].
AB  - Retropubic or transobturator insertions of suburethral tapes are the new gold
      standard surgical procedure for female stress urinary incontinence. Some women of
      childbearing age can be treated by a suburethral tape. There are at present no
      sufficient data to recommend a mode of delivery rather than another in these
      patients. We report the case of a young woman, cured of her urinary incontinence
      by a suburethral tape. A recurrence occurred after childbirth by vaginal route. A
      second suburethral tape made it possible to restore the continence. The patient
      became again pregnant. A preventive caesarean section was quite as ineffective to
      preserve the continence.

PMID- 18042419
TI  - Characterization of an alginate-based drug delivery system for neurological
      applications.
AB  - This paper presents a drug delivery system based on alginate gels. The
      biocompatibility, the flexibility in size and shape, and the ability to entrap
      biomolecules make alginate-based systems ideal for in vivo drug delivery.
      Specifically, by considering the target application of neural regeneration and
      neuroprotection, the issue of biocompatibility as well as morphologic
      compatibility (e.g. shape and size of an implant) have to be addressed. The
      authors describe various types of alginate gels; fibers of cylindrical shape
      resulted the best choice in terms of simplicity of realization, insertion and
      release effectiveness, as shown by preliminary in vivo assays. Consequently,
      fibers release is tested in vitro and theoretically modelled, in order to obtain
      mathematical correlations between the release kinetics and key parameters
      affecting the realization procedure.

PMID- 18042420
TI  - Rodent electroretinography: methods for extraction and interpretation of rod and
      cone responses.
AB  - The flash electroretinogram (ERG) represents a serial ensemble of neural
      responses that can be used to objectively evaluate retinal function on a layer-by
      layer basis. In this review, the seminal concepts of Granit are developed within
      the modern context to demonstrate how the ERG waveform can be decomposed to
      isolate the activity of individual neural populations and their circuitry. The
      contribution of rods and cones to the ERG waveform can be precisely defined with
      simple methods that yield the veridical cone response, which allows
      identification of rod-isolated components. This knowledge will afford an enhanced
      capacity to understand retinal development and ageing as well as to interpret the
      effects of insult, genetic manipulation and disease processes on photoreceptor
      and neuron-specific components. This review integrates conclusions drawn from a
      large body of past work and presents new data that enables the provision of
      detailed methodology for ERG assessment in rodents. Emphasis is placed on
      protocols that allow efficient acquisition of useful information for the major
      ERG components with minimal complexity. In particular, specific guidelines for
      the isolation of rod and cone contributions from the full-field ERG in rodents
      are provided. This is complemented with detailed and novel methodology for
      determining parameters that describe individual neuronal generators of rod and
      cone responses. The effect of stimulus energy on the kinetics of ERG response
      recovery and photopigment bleaching and regeneration are also discussed. The
      guidelines presented here are applicable to a wide range of investigations of
      retinal disease in rodent models.

PMID- 18042421
TI  - Nonmotor symptoms of Parkinson's disease: prevalence and awareness of patients
      and families.
AB  - The aim of this study was to explore the prevalence of nonmotor symptoms in
      Parkinson's disease (PD) and the patients' and family members' awareness of these
      symptoms. We evaluated 74 parkinsonian patients and 54 family members. Seventy
      three patients had more than one symptom (12.4+/-5.5 out of 30 symptoms on
      average). Nocturia was the most common in men and feeling sad in women. The
      average number of symptoms which patients knew to be related to PD was 5.2+/-6.8
      and to family members 7.7+/-6.5. Twenty-eight patients and five family members
      were unaware of the relationship between any of these symptoms and PD. For PD to
      be properly managed, nonmotor symptoms should be comprehensively assessed and
      patients and families informed that these are associated with PD.

PMID- 18042422
TI  - Paroxysmal dyskinesia with interictal myoclonus and dystonia: a report of two
      cases.
AB  - Idiopathic paroxysmal dyskinesias (PxD) are characterized by attacks of
      hyperkinetic movement, with no inter-ictal symptoms. We report two cases, one
      with paroxysmal kinesigenic dyskinesia and another with paroxysmal exercise
      induced dystonia, both of whom had myoclonus and dystonia between attacks. This
      previously unreported association highlights the heterogeneity of paroxysmal
      movement disorders.

PMID- 18042423
TI  - Decision making, impulsivity and time perception.
AB  - Time is an important dimension when individuals make decisions. Specifically, the
      time until a beneficial outcome can be received is viewed as a cost and is
      weighed against the benefits of the outcome. We propose that impulsive
      individuals experience time differently, that is with a higher cost. Impulsive
      subjects, therefore, overestimate the duration of time intervals and, as a
      consequence, discount the value of delayed rewards more strongly than do self
      controlled individuals. The literature on time perception and impulsivity,
      however, is not clear cut and needs a better theoretical foundation. Here, we
      develop the theoretical background on concepts of time perception, which could
      lead to an empirically based notion of the association between an altered sense
      of time and impulsivity.

PMID- 18042424
TI  - Diagnostic yield of sequential routine EEG and extended outpatient video-EEG
      monitoring.
AB  - OBJECTIVE: To investigate the diagnostic yield of outpatient video-EEG monitoring
      (OVEM) in patients with suspected but unconfirmed epilepsy. METHODS: OVEM data,
      comprised of 20-min video-EEG (REEG) followed by 4h of video-EEG monitoring
      (EXM), from 179 consecutive patients were retrospectively analyzed. Three
      diagnostic categories were defined: localization-related epilepsy (LRE),
      generalized epilepsy (GE), and nonepileptic seizures (NES). Outcome measures
      were: frequency of events; diagnostic yield of entire OVEM; relative yields of
      REEG alone and EXM after nondiagnostic REEG; EXM diagnostic rate (yield of EXM
      after nondiagnostic REEG/yield of entire OVEM). RESULTS: Habitual events occurred
      in 14 (8%) and 25 (15%) patients during REEG and EXM, respectively. Overall, OVEM
      was diagnostic in 90/179 patients (50%): LRE 21%; GE 15%; NES 15%. REEG alone was
      diagnostic in 49/179 patients (27%): LRE 7%; GE 13%; NES 7%. After nondiagnostic
      REEG, the subsequent EXM was diagnostic in 41/130 patients (32%): LRE (n=24); GE
      (n=2); NES (n=15). The EXM diagnostic rate (95% confidence interval) was 0.65
      (0.47-0.80) for LRE, 0.08 (0.01-0.25) for GE, and 0.56 (0.35-0.75) for NES.
      CONCLUSIONS: OVEM is useful in establishing and classifying epilepsy. Compared to
      REEG, EXM is relatively more beneficial in the diagnosis of LRE and NES rather
      than GE. SIGNIFICANCE: This study outlines the benefits of extended outpatient
      video-EEG monitoring after nondiagnostic routine EEG.

PMID- 18042425
TI  - Long-term event-related potential changes following organophosphorus insecticide
      poisoning.
AB  - OBJECTIVE: To determine prolonged effects of organophosphorus (OP) insecticide
      poisoning on cognitive event-related potentials (ERPs). METHODS: ERPs of a group
      of 32 patients recovered from cholinergic phase of OP insecticide poisoning were
      compared with those of two matched control groups: 32 healthy volunteers and nine
      patients hospitalised with paracetamol overdose. A follow-up assessment was done
      in 21 patients (66% of the initial sample) 6 months after OP intoxication and the
      findings were compared with their initial ERP data. RESULTS: Patients showed
      highly significant prolongation of P300 latency, compared to healthy controls
      (p=0.003) and the controls with paracetamol overdose (p=0.016). Follow-up ERP
      findings of the patients revealed that this impairment remained unchanged even 6
      months after OP poisoning (p=0.790). There was no significant difference in N100,
      P200 and N200 latencies or P300 amplitude either among the groups or between the
      two assessments of the patients with OP poisoning. CONCLUSIONS: Our results
      suggest that acute OP poisoning causes a delay in cognitive processes involved in
      stimulus classification, lasting at least for 6 months. SIGNIFICANCE: These
      findings highlight the possibility of development of long-lasting cognitive
      deficits following OP insecticide poisoning, and warrant longer-term prospective
      studies to determine whether this impairment is permanent.

PMID- 18042426
TI  - Investigation of paroxysmal dystonia in a patient with multiple sclerosis: a
      transcranial magnetic stimulation study.
AB  - OBJECTIVE: To study the pathogenesis of paroxysmal dystonia affecting the right
      body side in a patient with a demyelinating lesion in the descending motor
      pathways, also involving the basal ganglia. METHODS: Single-pulse transcranial
      magnetic stimulation (TMS) was applied to study motor evoked potentials (MEPs)
      and the following silent periods (SPs) in the first dorsal interosseous muscle
      (FDI) of both sides and in the right extensor carpi radialis muscle (ECR) during
      voluntary contractions performed outside the dystonic attacks. During the
      dystonic paroxysms, single-pulse TMS was used to investigate the time course of
      MEPs and SPs in both FDI and ECR of the right side. Furthermore, paired-pulse TMS
      was applied at rest to investigate short-interval intracortical inhibition (SICI)
      and intracortical facilitation (ICF) in both FDI muscles. RESULTS: At rest SICI
      and ICF were normal in both motor cortices. During voluntary contraction the MEP
      was smaller and the SP was longer in the affected FDI than in the contralateral.
      During the paroxysms, the MEPs and SPs were suppressed in comparison with the
      responses elicited during voluntary contraction. CONCLUSIONS: These results fit
      well with the theory of ephaptic excitement of corticospinal axons for the
      pathogenesis of paroxysmal dystonia due to a demyelinating lesion. SIGNIFICANCE:
      Identification of the mechanisms underlying paroxysmal dystonia in demyelinating
      disorders extends our knowledge on the pathophysiology of dystonia.

PMID- 18042427
TI  - Persistent mirror movements for over sixty years: the underlying mechanisms in a
      cerebral palsy patient.
AB  - OBJECTIVE: To determine the mechanisms underlying the mirroring of distal
      movements in both upper and lower limbs present in one individual from birth.
      METHODS: Transcranial magnetic stimulation (TMS), magnetic resonance imaging
      (MRI), functional magnetic resonance imaging (fMRI), voluntary and reflexly
      evoked electromyograms (EMG) and force measurements were used to obtain
      information about the motor pathways responsible for the mirror movements.
      RESULTS: MRI showed a significant loss of brain tissue from one hemisphere and
      fMRI indicated a significant functional reorganization had taken place. An
      obligatory mirroring of voluntary movement on the sound side occurs on the
      affected side, but some independent movement can be produced on the affected
      side, if enabled by weak contractions on the sound side. TMS mapping revealed
      bilateral projections from one hemisphere and virtually absent projections from
      the primary motor cortex of the other hemisphere. Spinal reflexes were restricted
      to the stimulated side. Transcortical reflexes were evoked bilaterally from the
      sound side, but not from the affected side. CONCLUSIONS: The physiological and
      imaging data are consistent with a mirroring from the intact motor cortex via the
      supplementary motor area. SIGNIFICANCE: Mirror movements in this individual
      represent a major cortical reorganization and a partial solution to the neonatal
      loss of substantial amounts of brain tissue.

PMID- 18042428
TI  - A patient with a "Normal" sleep study.

PMID- 18042429
TI  - Global diversity and biogeography of Skeletonema species (bacillariophyta).
AB  - Recent studies have shown that the cosmopolitan diatom Skeletonema costatum sensu
      lato is composed of several morphologically and genetically distinct species. To
      assess whether the separate species have a cosmopolitan distribution, we analysed
      184 strains from marine and estuarine sites worldwide. We identified the strains
      using light and electron microscopy, and we sequenced the hyper-variable region
      of nuclear LSU rDNA. All recently described species were genetically distinct,
      and all but two were morphologically distinct. Variability was found for the only
      ultrastructural character used to distinguish Skeletonema dohrnii and S. marinoi,
      which cannot be identified based on morphology alone. Furthermore, multiple
      genetically distinct taxa, which may represent cryptic species, were found within
      the S. menzelii and S. tropicum clades. We found that all currently recognized
      species of Skeletonema are widespread, however, gaps seem to occur in their
      geographical ranges. For example, some species are found in both the northern and
      southern temperate latitudes whereas other species appear to have only
      subtropical to tropical ranges. Skeletonema pseudocostatum and S. grethae seem to
      have more restricted geographical ranges because the former was not found along
      American coasts and the latter was encountered only in US waters. A taxonomic
      update is provided for Skeletonema strains currently available in several culture
      collections, which could aid reinterpretation of results obtained in comparative
      studies using these strains.

PMID- 18042430
TI  - Use of 70-gene signature to predict prognosis of patients with node-negative
      breast cancer: a prospective community-based feasibility study (RASTER).
AB  - BACKGROUND: A microarray-based 70-gene prognosis signature might improve the
      selection of patients with node-negative breast cancer for adjuvant systemic
      treatment. The main aims of this MicroarRAy PrognoSTics in Breast CancER (RASTER)
      study were to assess prospectively the feasibility of implementation of the 70
      gene prognosis signature in community-based settings and its effect on adjuvant
      systemic treatment decisions when considered with treatment advice formulated
      from the Dutch Institute for Healthcare Improvement (CBO) and other guidelines.
      METHODS: Between January, 2004 and December, 2006, 812 women aged under 61 years
      with primary breast carcinoma (clinical T1-4N0M0) were enrolled. Fresh tumour
      samples were collected in 16 hospitals in the Netherlands within 1 h after
      surgery. Clinicopathological factors were collected and microarray analysis was
      done with a custom-designed array chip that assessed the mRNA expression index of
      the 70 genes previously identified for the prognostic signature. Patients with a
      "good" signature were deemed to have a good prognosis and, therefore, could be
      spared adjuvant systemic treatment with its associated adverse effects, whereas
      patients with a "poor" signature were judged to have a poor prognosis and should
      be considered for adjuvant systemic treatment. Concordance between risk predicted
      by the prognosis signature and risk predicted by commonly used
      clinicopathological guidelines (ie, St Gallen guidelines, Nottingham Prognostic
      Index, and Adjuvant! Online) was assessed. FINDINGS: Of 585 eligible patients,
      158 patients were excluded because of sampling failure (n=128) and incorrect
      procedure (n=30). Prognosis signatures were assessed in 427 patients. The 70-gene
      prognosis signature identified 219 (51%) patients with good prognosis and 208
      (49%) patients with poor prognosis. The Dutch CBO guidelines identified 184
      patients (43%) with poor prognosis, which was discordant with those findings
      obtained with the prognosis signature in 128 (30%) patients. Oncologists
      recommended adjuvant treatment in 203 (48%) patients based on Dutch CBO
      guidelines, in 265 (62%) patients if the guidelines were used with the prognosis
      signature, and in 259 (61%) patients if Dutch CBO guidelines, prognosis
      signature, and patients' preferences for treatment were all taken into account.
      Adjuvant! Online guidelines identified more patients with poor prognosis than did
      the signature alone (294 [69%]), and discordance with the signature occurred in
      160 (37%) patients. St Gallen guidelines identified 353 (83%) patients with poor
      prognosis with the signature and discordance in 168 (39%) patients. Nottingham
      Prognostic Index recorded 179 (42%) patients with poor prognosis with the
      signature and discordance in 117 (27%) patients. INTERPRETATION: Use of the
      prognosis signature is feasible in Dutch community hospitals. Adjuvant systemic
      treatment was advised less often when the more restrictive Dutch CBO guidelines
      were used compared with that finally given after use of the prognosis signature.
      For the other guidelines assessed, less adjuvant chemotherapy would be given when
      the data based on prognosis signature alone are used, which might spare patients
      from adverse effects and confirms previous findings. Future studies should assess
      whether use of the prognosis signature could improve survival or equal survival
      while avoiding unnecessary adjuvant systemic treatment without affecting
      patients' survival, and further assess the factors that physicians use to
      recommend adjuvant systemic treatment.

PMID- 18042432
TI  - A network to monitor antimalarial drug resistance: a plan for moving forward.
AB  - The spread of resistance to antimalarial drugs has required changes in the
      recommended first-line treatment for falciparum malaria in almost all regions.
      Most drugs recommended currently are combinations of a long-acting antimalarial
      and an artemisinin derivative. This article presents the rationale for
      establishing a web-based, open-access database of antimalarial drug resistance
      and efficacy: the World Antimalarial Resistance Network (WARN). The goal of this
      network is to assemble the tools and information that will enable the malaria
      community to collate, analyze and share contemporary information on antimalarial
      drug efficacy in all endemic regions so that decisions on antimalarial-drug use
      are based on solid evidence.

PMID- 18042431
TI  - How does HTLV-I persist despite a strong cell-mediated immune response?
AB  - Human T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that
      infects human CD4(+) T lymphocytes. Despite its presence in T cells, HTLV-1
      causes little overt immunosuppression. This host-virus relationship has therefore
      been exploited as an excellent model system for studying the dynamic interaction
      between a persistent retrovirus and the normal human immune system. We use a
      combination of mathematical and experimental techniques to identify key factors
      on both sides of the in vivo host-virus interaction that significantly determine
      HTLV-I proviral load and disease risk. We develop a model to describe how these
      factors interact to enable viral persistence.

PMID- 18042433
TI  - Nurses' attitudes, beliefs and confidence levels regarding care for those who
      abuse alcohol: impact of educational intervention.
AB  - Alcohol abuse is a worldwide public health concern. Nurses, representing the
      largest body of health care providers, are a potential resource to provide
      screening and brief intervention for patients with alcohol problems. This study
      evaluates the effect of an educational intervention on the attitudes, beliefs,
      and confidence levels of nurses regarding screening and brief intervention for
      alcohol problems. One hundred eighty-one students at Vanderbilt University School
      of Nursing participated in a four-hour educational intervention to train
      providers in brief negotiated intervention (BNI) for screening, early detection
      and brief treatment of alcohol problems. Participants completed questionnaires
      before and after this training. Analysis of the data using paired t-test and one
      way analysis of variance showed statistically significant positive change in the
      nurses' attitudes, beliefs, and confidence levels regarding alcohol abuse and its
      treatment after the educational intervention. For example, the percentage of
      nurses who reported always having confidence in assessing patients' readiness to
      change their behavior increased from 8.3% to 23.5% after training. In conclusion,
      the BNI educational intervention can be effective in promoting positive changes
      among nurses in attitudes, beliefs, and confidence levels regarding alcohol abuse
      and its treatment.

PMID- 18042434
TI  - Lecturers' experiences and perspectives of using an objective structured clinical
      examination.
AB  - The purpose of this paper is to present the findings that emerged from a
      qualitative study which explored nurse educators' experiences and perspectives of
      assessing students' clinical competence using an objective structured clinical
      examination (OSCE), and to address the challenges pertaining to the assessment.
      OSCEs have been researched internationally; however, exploration within an Irish
      context is limited. The current study is timely as the findings are relevant in
      light of the ongoing debate about OSCEs. The data for this study was collected
      using two focus groups in one institution in the Republic of Ireland. Two main
      themes emerged: OSCE preparation and assessment process. It is envisaged that the
      outcome of this study will enable nurse educators to recognise both the potential
      and the contribution of OSCEs to the curriculum and motivate nurse educators to
      increase students' exposure to this assessment strategy. The need to adapt and
      become cognisant of the major changes in the 'real' healthcare world will
      continue to challenge nurse educators.

PMID- 18042436
TI  - Periodic erythroexchange is an effective strategy for high risk paediatric
      patients with sickle-cell disease.
AB  - We performed an 11 year retrospective study on 34 sickle-cell paediatric
      patients, focusing on efficacy, safety and costs of an exchange transfusion
      program in 13 high risk patients. A good clinical control with improvement in
      patients' quality of life, no disease related complications, no significant iron
      overload and no procedure related side effects were observed during periodic
      erythroexchange. Costs of periodic erythroexchange versus chronic transfusion
      regimen were comparable. Periodic erythroexchange appeared a good alternative to
      chronic transfusion regimen for controlling the most severe forms of disease,
      particularly in patients who do not tolerate or do not respond to hydroxyurea.

PMID- 18042438
TI  - An overview of unresolved inherent problems associated with red cell transfusion
      and potential use of artificial oxygen carriers and ECO-RBC: current
      status/future trends.
AB  - This manuscript deals with why we need alternatives to liquid stored RBC
      highlighting some of the unresolved inherent problems related to red cell storage
      lesion and their potential impacts on the clinical outcomes and transfusion
      complications. The promise of several potential alternatives to red cell
      transfusions such as: Perfluorocarbon; Modified Hb-based oxygen carriers and
      newer design of Hb-based oxygen carriers are reviewed. It is noteworthy to say
      that since the first introduction of these oxygen carriers, almost five decades
      ago, the only successful drive has been to prepare safer and more convenient
      oxygen carriers, for enhancing the quality of life of recipients and their usage,
      either as substitutes to red cell transfusion or even as the bridge, remains
      patchy. Moreover, as new products with better characteristics become available
      the older products from the competitors are withdrawn. Finally, the current
      progress on universal RBC, known as ECO-cells is highlighted and, in the future
      perspectives, some of the current efforts in making the red cells transfusion
      safer and more efficacious are briefly addressed.

PMID- 18042439
TI  - LDL apheresis in Italy.

PMID- 18042440
TI  - Dystrobrevin and dystrophin family gene expression in zebrafish.
AB  - Dystrophin/dystrobrevin superfamily proteins play structural and signalling roles
      at the plasma membrane of many cell types. Defects in them or the associated
      multiprotein complex cause a range of neuromuscular disorders. Members of the
      dystrophin branch of the family form heterodimers with members of the
      dystrobrevin branch, mediated by their coiled-coil domains. To determine which
      combinations of these proteins might interact during embryonic development, we
      set out to characterise the gene expression pattern of dystrophin and
      dystrobrevin family members in zebrafish. gamma-dystrobrevin (dtng), a novel
      dystrobrevin recently identified in fish, is the predominant form of dystrobrevin
      in embryonic development. Dtng and dmd (dystrophin) have similar spatial and
      temporal expression patterns in muscle, where transcripts are localized to the
      ends of differentiated fibres at the somite borders. Dtng is expressed in the
      notochord while dmd is expressed in the chordo-neural hinge and then in floor
      plate and hypochord. In addition, dtng is dynamically expressed in rhombomeres 2
      and 4-6 of the hindbrain and in the ventral midbrain. alpha-dystrobrevin (dtna)
      is expressed widely in the brain with particularly strong expression in the
      hypothalamus and the telencephalon; drp2 is also expressed widely in the brain.
      Utrophin expression is found in early pronephros and lateral line development and
      utrophin and dystrophin are both expressed later in the gut. beta-dystrobrevin
      (dtnb) is expressed in the pronephric duct and widely at low levels. In summary,
      we find clear instances of co-expression of dystrophin and dystrobrevin family
      members in muscle, brain and pronephric duct development and many examples of
      strong and specific expression of members of one family but not the other, an
      intriguing finding given the presumed heterodimeric state of these molecules.

PMID- 18042441
TI  - A single centre experience of liver disease in adults with cystic fibrosis 1995
      2006.
AB  - BACKGROUND: Liver disease is an important cause of death in adults with cystic
      fibrosis (CF). Ursodeoxycholic acid (UDCA) may slow progression. Managing varices
      and timely evaluation for liver transplantation are important. METHODS: Adults
      with CF underwent annual review. Abnormalities of liver function tests or
      ultrasound prompted referral to the CF/liver clinic where UDCA was commenced.
      Endoscopic surveillance for varices was undertaken if ultrasound suggested portal
      hypertension. RESULTS: 154 patients were followed for a median 5 years. 43 had
      significant liver disease, 29 had cirrhosis with portal hypertension and 14 had
      ultrasound evidence of cirrhosis without portal hypertension. All started UDCA.
      Only one patient developed chronic liver failure and none required liver
      transplantation. 27 underwent endoscopy; 1 required variceal banding, the others
      had insignificant varices. Ultrasound was normal in 97 patients while five had
      steatosis; nine further patients had splenomegaly but no other evidence of portal
      hypertension. Neither spleen size nor platelet count correlated with portal
      hypertension. CONCLUSIONS: Liver disease was common in adults with CF but disease
      progression was rare. Thus liver disease detected and closely monitored in adults
      appeared to have a milder course than childhood CF. Splenomegaly, unrelated to
      portal hypertension may be a consequence of CF.

PMID- 18042442
TI  - Comparison of ESI-MS interfaces for the analysis of UV-crosslinked peptide
      nucleic acid complexes.
AB  - In this report, the effectiveness of high performance liquid chromatography
      (HPLC) in conjunction with electrospray ionization mass spectrometry (ESI-MS) is
      examined as a tool for identifying the sites of crosslinking in a protein that
      has been photoreacted with a non-photolabeled oligonucleotide. ESI-MS and MALDI
      MS analyses preceded by off-line microflow and nanoflow HPLC, on-line microflow
      HPLC/ESI, and on-line nanoflow HPLC/ESI interfaces were performed in order to
      determine their relative effectiveness in separating mixtures of nucleopeptides
      and identifying sites of crosslinking on the individual components. The
      characteristics of these four techniques as well as possibilities for improving
      the analysis of nucleopeptides by ESI-MS are compared and discussed.

PMID- 18042443
TI  - Chiral bioanalysis of torcetrapib enantiomers in hamster plasma by normal-phase
      liquid chromatography and detection by atmospheric pressure chemical ionization
      tandem mass spectrometry.
AB  - A highly sensitive and enantioselective assay has been developed and validated
      for the estimation of torcetrapib (TTB) enantiomers [(+)-TTB and (-)-TTB] in
      hamster plasma with chiral liquid chromatography coupled to tandem mass
      spectrometry with an atmospheric pressure chemical ionization interface in the
      negative-ion mode. The assay procedure involves liquid-liquid extraction of TTB
      enantiomers and IS (DRL-16126) from 100 microL hamster plasma with acetonitrile.
      TTB enantiomers were separated using n-hexane:propanol (80:20, v/v) at a flow
      rate of 0.7 mL/min on a Chiralpak AD column. The MS/MS ion transitions monitored
      were 599.2-->340.2 for TTB and 623.2-->298.1 for IS. Absolute recovery was found
      to be between 64 and 68% for TTB enantiomers and >100% for IS. The standard
      curves for TTB enantiomers were linear (r(2)>0.995) in the concentration range 5
      2500 ng/mL for each enantiomer with an LLOQ of 5 ng/mL for each enantiomer. The
      inter- and intra-day precisions were in the range of 10.5-12.4 and 9.15-11.5% and
      3.75-12.9 and 5.16-12.5% for (+)-TTB and (-)-TTB, respectively. Accuracy in the
      measurement of quality control (QC) samples was in the range 91.3-105 and 88.6
      111% for (+)-TTB and (-)-TTB, respectively. This novel method has been applied to
      the study of stereoselective oral pharmacokinetics of (-)-TTB.

PMID- 18042444
TI  - The versatility of the free lateral arm flap in head and neck soft tissue
      reconstruction: clinical experience of 210 cases.
AB  - A study of the authors' experience with 210 free lateral arm flaps used to repair
      head and neck oncological defects over an 8-year period. Patients' ages ranged
      from 4 to 83 years (average: 49.7 years). One hundred and forty-one were male and
      66 female. Three patients received two consecutive flaps each. They were used to
      reconstruct: the tongue, 53 cases; retromolar trigone, 42 cases; soft/hard
      palate, 34 cases; skin/facial contour, 19 cases; hypopharynx, 17 cases; buccal
      mucosa, 12 cases; lips, five cases. Flap cutaneous dimensions ranged from 4 x 2
      cm to 17 x 8 cm. Flap was composed of: skin and fascia, 18 cases; sensate
      (neurovascular) skin, six cases; subcutaneous fat tissue, five cases; skin and
      vascularised nerve graft, three cases, skin and partial triceps muscle, three
      cases. Nerve coaptations were performed for all lip reconstructions. All flaps
      survived except for nine (success rate: 95.2%). Severe postoperative clinical
      complications preceded flap failure and death in two cases. All but six donor
      sites were closed primarily. Complications related to the donor site were:
      paresthesia of the forearm, 210 cases; dog ear, 16 cases; hypertropic scar, 14
      cases; weakness, nine cases; haematoma, five cases; seroma, three cases;
      dehiscence, one case. Radial nerve injury was not observed in this series. The
      lateral arm flap can be considered safe and versatile for most soft tissue head
      and neck microsurgical reconstructions. The possibility of sensory recovery
      through neural anastomoses and low donor site morbidity enhances its efficiency.

PMID- 18042445
TI  - Giant phyllodes tumour of the breast.
AB  - Phyllodes tumours are fibroepithelial lesions and count for 0.4% of breast
      tumours. Telling the difference between phyllodes tumours and fibroadenomas is
      sometimes difficult but of importance because wide resection is the mainstay of
      treatment for phyllodes tumours. We present a female patient, 55 years old with a
      giant phyllodes tumour (38 x 31 x 23 cm) of the breast. The breast reconstruction
      was done using a pedicled transverse rectus abdominis myocutaneous (TRAM) flap.

PMID- 18042446
TI  - A quorum on bacterial programmed cell death.
AB  - A recent article in Science (Kolodkin-Gal et al., 2007) reported a novel
      programmed cell death mechanism for Escherichia coli that occurs during cellular
      overcrowding via the release of a fratricidal pentapeptide derived from the
      metabolic enzyme glucose-6-phosphate dehydrogenase.

PMID- 18042447
TI  - Breaking the cycle of translation.
AB  - In a recent issue of Molecular Cell, Trobro and Aqvist (2007) reported
      mechanistic insight into release factor-induced peptide hydrolysis. Now, in this
      issue, the Green research group establishes unexpected complexity in decoding
      translation stop codons (Youngman et al., 2007).

PMID- 18042448
TI  - To kill or to arrest: that is the new question for Apaf-1.
AB  - In this issue of Molecular Cell, Zermati et al. (2007) report that Apaf-1 is
      essential for the DNA damage-induced intra-S phase checkpoint response. This new
      role for Apaf-1 is unrelated to its proapoptotic function but is evolutionarily
      conserved in Ced-4.

PMID- 18042449
TI  - Send in the clamps: control of DNA translesion synthesis in eukaryotes.
AB  - The replication of damaged DNA templates by translesion synthesis (TLS) is
      associated with mutagenesis and carcinogenesis. This perspective discusses the
      different levels at which TLS may be controlled and proposes a model for TLS of
      severely helix-distorting DNA lesions that includes a decisive role for the Rad9
      Hus1-Rad1 DNA-damage-signaling clamp. The dual involvement of this clamp in both
      DNA-damage signaling and TLS may have profound implications in determining
      cellular responses to DNA damage.

PMID- 18042450
TI  - Stop codon recognition by release factors induces structural rearrangement of the
      ribosomal decoding center that is productive for peptide release.
AB  - Peptide release on the ribosome is catalyzed in the large subunit peptidyl
      transferase center by release factors on recognition of stop codons in the small
      subunit decoding center. Here we examine the role of the decoding center in this
      process. Mutation of decoding center nucleotides or removal of 2'OH groups from
      the codon--deleterious in the related process of tRNA selection--has only mild
      effects on peptide release. The miscoding antibiotic paromomycin, which binds the
      decoding center and promotes the critical steps of tRNA selection, instead
      dramatically inhibits peptide release. Differences in the kinetic mechanism of
      paromomycin inhibition on stop and sense codons, paired with correlated
      structural changes monitored by chemical footprinting, suggest that recognition
      of stop codons by release factors induces specific structural rearrangements in
      the small subunit decoding center. We propose that, like other steps in
      translation, the specificity of peptide release is achieved through an induced
      fit mechanism.

PMID- 18042451
TI  - Characterization of an ERAD pathway for nonglycosylated BiP substrates, which
      require Herp.
AB  - To investigate the disposal of nonglycosylated BiP substrates, we used a
      nonsecreted kappa LC, which exists in partially (ox1) and completely (ox2)
      oxidized states. The ox2 form is partially reduced in order to be degraded, and
      only the ox1 form is ubiquitinated and associates with both Herp and Derlin-1.
      Herp is in a complex with ubiquitinated proteins and with the 26S proteasome,
      suggesting that it plays a role in linking substrates with the proteasome.
      Overexpressed Herp also interacts with two other BiP substrates, but not with two
      calnexin substrates. Either expression of p97 or Hrd1 mutants, which are in a
      complex with Herp and Derlin-1, or reduction of Herp levels inhibited the
      degradation of the BiP substrates, whereas the latter had no effect on the
      degradation of the calnexin substrates. This result suggests that there is some
      distinction in the pathways used to dispose of these two types of ERAD
      substrates.

PMID- 18042452
TI  - Analysis of the function of Spire in actin assembly and its synergy with formin
      and profilin.
AB  - The Spire protein, together with the formin Cappuccino and profilin, plays an
      important role in actin-based processes that establish oocyte polarity. Spire
      contains a cluster of four actin-binding WH2 domains. It has been shown to
      nucleate actin filaments and was proposed to remain bound to their pointed ends.
      Here we show that the multifunctional character of the WH2 domains allows Spire
      to sequester four G-actin subunits binding cooperatively in a tight SA(4) complex
      and to nucleate, sever, and cap filaments at their barbed ends. Binding of Spire
      to barbed ends does not affect the thermodynamics of actin assembly at barbed
      ends but blocks barbed end growth from profilin-actin. The resulting Spire
      induced increase in profilin-actin concentration enhances processive filament
      assembly by formin. The synergy between Spire and formin is reconstituted in an
      in vitro motility assay, which provides a functional basis for the genetic
      interplay between Spire, formin, and profilin in oogenesis.

PMID- 18042453
TI  - Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent
      Grp1 family Arf GTPase exchange factors.
AB  - Arf GTPases regulate membrane trafficking and actin dynamics. Grp1, ARNO, and
      Cytohesin-1 comprise a family of phosphoinositide-dependent Arf GTPase exchange
      factors with a Sec7-pleckstrin homology (PH) domain tandem. Here, we report that
      the exchange activity of the Sec7 domain is potently autoinhibited by conserved
      elements proximal to the PH domain. The crystal structure of the Grp1 Sec7-PH
      tandem reveals a pseudosubstrate mechanism of autoinhibition in which the linker
      region between domains and a C-terminal amphipathic helix physically block the
      docking sites for the switch regions of Arf GTPases. Mutations within either
      element result in partial or complete activation. Critical determinants of
      autoinhibition also contribute to insulin-stimulated plasma membrane recruitment.
      Autoinhibition can be largely reversed by binding of active Arf6 to Grp1 and by
      phosphorylation of tandem PKC sites in Cytohesin-1. These observations suggest
      that Grp1 family GEFs are autoregulated by mechanisms that depend on plasma
      membrane recruitment for activation.

PMID- 18042454
TI  - GSK-3-mediated phosphorylation enhances Maf-transforming activity.
AB  - The Maf oncoproteins are b-Zip transcription factors of the AP-1 superfamily.
      They are involved in developmental, metabolic, and tumorigenic processes. Maf
      proteins are overexpressed in about 50% of human multiple myelomas. Here, we show
      that Maf-transforming activity is controlled by GSK-3-dependent phosphorylation
      and that phosphorylation by GSK-3 can increase the oncogenic activity of a
      protein. Using microarray analysis, we identify a gene-expression subprogram
      regulated by GSK-3-mediated Maf phosphorylation involved in extracellular matrix
      remodeling and relevant to cancer progression. We also demonstrate that GSK-3
      triggers MafA sequential phosphorylation on residues S61, T57, T53, and S49,
      inducing its ubiquitination and degradation. Paradoxically, this phosphorylation
      increases MafA-transcriptional activity through the recruitment of the
      coactivator P/CAF. We further demonstrate that P/CAF protects MafA from
      ubiquitination and degradation, suggesting that, upon the release of the
      coactivator complex, MafA becomes polyubiquitinated and degraded to allow the
      response to terminate.

PMID- 18042455
TI  - Systematic identification of C. elegans miRISC proteins, miRNAs, and mRNA targets
      by their interactions with GW182 proteins AIN-1 and AIN-2.
AB  - MicroRNAs (miRNAs) regulate gene expression for diverse functions, but only a
      limited number of mRNA targets have been experimentally identified. We show that
      GW182 family proteins AIN-1 and AIN-2 act redundantly to regulate the expression
      of miRNA targets, but not miRNA biogenesis. Immunoprecipitation (IP) and mass
      spectrometry indicate that AIN-1 and AIN-2 interact only with miRNA-specific
      Argonaute proteins ALG-1 and ALG-2 and with components of the core translational
      initiation complex. Known miRNA targets are enriched in AIN-2 complexes,
      correlating with the expression of corresponding miRNAs. Combining IP with
      pyrosequencing and microarray analysis of RNAs associated with AIN-1/AIN-2, we
      identified 106 previously annotated miRNAs plus nine new candidate miRNAs, but
      nearly no siRNAs, and more than 3500 potential miRNA targets, including nearly
      all known ones. Our results demonstrate an effective biochemical approach to
      systematically identify miRNA targets and provide valuable insights regarding the
      properties of miRNA effector complexes.

PMID- 18042456
TI  - Structure of the Pho85-Pho80 CDK-cyclin complex of the phosphate-responsive
      signal transduction pathway.
AB  - The ability to sense and respond appropriately to environmental changes is a
      primary requirement of all living organisms. In response to phosphate limitation,
      Saccharomyces cerevisiae induces transcription of a set of genes involved in the
      regulation of phosphate acquisition from the ambient environment. A signal
      transduction pathway (the PHO pathway) mediates this response, with Pho85-Pho80
      playing a vital role. Here we report the X-ray structure of Pho85-Pho80, a
      prototypic structure of a CDK-cyclin complex functioning in transcriptional
      regulation in response to environmental changes. The structure revealed a
      specific salt link between a Pho85 arginine and a Pho80 aspartate that makes
      phosphorylation of the Pho85 activation loop dispensable and that maintains a
      Pho80 loop conformation for possible substrate recognition. It further showed two
      sites on the Pho80 cyclin for high-affinity binding of the transcription factor
      substrate (Pho4) and the CDK inhibitor (Pho81) that are markedly distant to each
      other and the active site.

PMID- 18042457
TI  - Nonapoptotic role for Apaf-1 in the DNA damage checkpoint.
AB  - Apaf-1 is an essential factor for cytochrome c-driven caspase activation during
      mitochondrial apoptosis but has also an apoptosis-unrelated function. Knockdown
      of Apaf-1 in human cells, knockout of apaf-1 in mice, and loss-of-function
      mutations in the Caenorhabditis elegans apaf-1 homolog ced-4 reveal the
      implication of Apaf-1/CED-4 in DNA damage-induced cell-cycle arrest. Apaf-1 loss
      compromised the DNA damage checkpoints elicited by ionizing irradiation or
      chemotherapy. Apaf-1 depletion reduced the activation of the checkpoint kinase
      Chk1 provoked by DNA damage, and knockdown of Chk1 abrogated the Apaf-1-mediated
      cell-cycle arrest. Nuclear translocation of Apaf-1, induced in vitro by exogenous
      DNA-damaging agents, correlated in non-small cell lung cancer (NSCLC) with the
      endogenous activation of Chk-1, suggesting that this pathway is clinically
      relevant. Hence, Apaf-1 exerts two distinct, phylogenetically conserved roles in
      response to mitochondrial membrane permeabilization and DNA damage. These data
      point to a role for Apaf-1 as a bona fide tumor suppressor.

PMID- 18042458
TI  - Sae2 is an endonuclease that processes hairpin DNA cooperatively with the
      Mre11/Rad50/Xrs2 complex.
AB  - Mre11/Rad50 complexes in all organisms function in the repair of DNA double
      strand breaks. In budding yeast, genetic evidence suggests that the Sae2 protein
      is essential for the processing of hairpin DNA intermediates and meiotic double
      strand breaks by Mre11/Rad50 complexes, but the biochemical basis of this
      functional relationship is not known. Here we demonstrate that recombinant Sae2
      binds DNA and exhibits endonuclease activity on single-stranded DNA independently
      of Mre11/Rad50 complexes, but hairpin DNA structures are cleaved cooperatively in
      the presence of Mre11/Rad50 or Mre11/Rad50/Xrs2. Hairpin structures are not
      processed at the tip by Sae2 but rather at single-stranded DNA regions adjacent
      to the hairpin. Truncation and missense mutants of Sae2 inactivate this
      endonuclease activity in vitro and fail to complement Deltasae2 strains in vivo
      for meiosis and recombination involving hairpin intermediates, suggesting that
      the catalytic activities of Sae2 are important for its biological functions.

PMID- 18042459
TI  - Structural mechanism of organic hydroperoxide induction of the transcription
      regulator OhrR.
AB  - The Xanthomonas campestris transcription regulator OhrR contains a reactive
      cysteine residue (C22) that upon oxidation by organic hydroperoxides (OHPs) forms
      an intersubunit disulphide bond with residue C127'. Such modification induces the
      expression of a peroxidase that reduces OHPs to their less toxic alcohols. Here,
      we describe the structures of reduced and OHP-oxidized OhrR, visualizing the
      structural mechanism of OHP induction. Reduced OhrR takes a canonical MarR family
      fold with C22 and C127' separated by 15.5 A. OHP oxidation results in the
      disruption of the Y36'-C22-Y47' interaction network and dissection of helix
      alpha5, which then allows the 135 degrees rotation and 8.2 A translation of
      C127', formation of the C22-C127' disulphide bond, and alpha6-alpha6' helix
      swapped reconfiguration of the dimer interface. These changes result in the 28
      degrees rigid body rotations of each winged helix-turn-helix motif and DNA
      dissociation. Similar effector-induced rigid body rotations are expected for most
      MarR family members.

PMID- 18042460
TI  - Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of
      transcription postinitiation factors and pre-mRNA splicing.
AB  - Trimethylation of histone H3 on lysine 4 (H3K4me3) localizes near the 5' region
      of genes and is tightly associated with active loci. Several proteins, such as
      CHD1, BPTF, JMJD2A, and the ING tumor suppressor family, directly recognize this
      lysine methyl mark. However, how H3K4me3 recognition participates in active
      transcription remains poorly characterized. Here we identify specific CHD1
      interacting proteins via H3K4me3 affinity purification, including numerous
      factors mediating postinitiation events. Conventional biochemical purification
      revealed a stable complex between CHD1 and components of the spliceosome.
      Depletion of CHD1 in extracts dramatically reduced splicing efficiency in vitro,
      indicating a functional link between CHD1 and the spliceosome. Knockdown of CHD1
      and H3K4me3 levels by siRNA reduced association of U2 snRNP components with
      chromatin and, more importantly, altered the efficiency of pre-mRNA splicing on
      active genes in vivo. These findings suggest that methylated H3K4 serves to
      facilitate the competency of pre-mRNA maturation through the bridging of
      spliceosomal components to H3K4me3 via CHD1.

PMID- 18042461
TI  - Structural basis for lower lysine methylation state-specific readout by MBT
      repeats of L3MBTL1 and an engineered PHD finger.
AB  - Human L3MBTL1, which contains three malignant brain tumor (MBT) repeats, binds
      monomethylated and dimethylated lysines, but not trimethylated lysines, in
      several histone sequence contexts. In crystal structures of L3MBTL1 complexes,
      the monomethyl- and dimethyllysines insert into a narrow and deep cavity of
      aromatic residue-lined pocket 2, while a proline ring inserts into shallower
      pocket 1. We have also engineered a single Y to E substitution within the
      aromatic cage of the BPTF PHD finger, resulting in a reversal of binding
      preference from trimethyl- to dimethyllysine in an H3K4 sequence context. In both
      the "cavity insertion" (L3MBTL1) and "surface groove" (PHD finger) modes of
      methyllysine recognition, a carboxylate group both hydrogen bonds and ion pairs
      to the methylammonium proton. Our structural and binding studies of these two
      modules provide insights into the molecular principles governing the decoding of
      lysine methylation states, thereby highlighting a methylation state-specific
      layer of histone mark readout impacting on epigenetic regulation.

PMID- 18042462
TI  - A genome-wide RNA interference screen reveals that variant histones are necessary
      for replication-dependent histone pre-mRNA processing.
AB  - Metazoan replication-dependent histone mRNAs are not polyadenylated and instead
      end in a conserved stem loop that is the cis element responsible for coordinate
      posttranscriptional regulation of these mRNAs. Using biochemical approaches, only
      a limited number of factors required for cleavage of histone pre-mRNA have been
      identified. We therefore performed a genome-wide RNA interference screen in
      Drosophila cells using a GFP reporter that is expressed only when histone pre
      mRNA processing is disrupted. Four of the 24 genes identified encode proteins
      also necessary for cleavage/polyadenylation, indicating mechanistic conservation
      in formation of different mRNA 3' ends. We also unexpectedly identified the
      histone variants H2Av and H3.3A/B. In H2Av mutant cells, U7 snRNP remains active
      but fails to accumulate at the histone locus, suggesting there is a regulatory
      pathway that coordinates the production of variant and canonical histones that
      acts via localization of essential histone pre-mRNA processing factors.

PMID- 18042463
TI  - Biochemical characterization of genetic mutations of GPR56 in patients with
      bilateral frontoparietal polymicrogyria (BFPP).
AB  - Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic disease
      characterized by cortical malformation associated with GPR56 mutations of
      frameshift, splicing, and point mutations (Science 303:2033). All the missense
      point mutations are located in the regions predicted to be exposed at the cell
      surface, e.g. the N-terminal extracellular domain (ECD), the proteolytic site
      (GPS), and the extracellular loops of transmembrane domain (TM), implying
      functionally important interaction among these domains. Wild type GPR56 protein
      is cleaved at the GPCR protein cleavage site (GPS) and gives rise to two subunits
      (ECD and TM), which are transported to cell surface. We have shown that GPR56 GPS
      mutant protein is defective in cleavage and surface localization, while non-GPS
      mutant proteins are cleaved normally but still defective in surface localization.
      Furthermore, all the mutant proteins demonstrated different glycosylation pattern
      from that of wild-type protein. PNGase F and Endo H sensitivity assays suggests
      that the mutant proteins are trapped in endoplasmic reticulum (ER), preventing
      them from trafficking to Golgi where further glycosylation modification usually
      occurs before destination to cell surface. Therefore, the loss-of-function of all
      these missense mutations is primarily caused by their failure to localize to cell
      surface.

PMID- 18042464
TI  - Vesicle-associated membrane protein 7 (VAMP-7) is essential for target cell
      killing in a natural killer cell line.
AB  - Natural killer cells recognize and induce apoptosis in foreign, transformed or
      virus-infected cells through the release of perforin and granzymes from secretory
      lysosomes. Clinically, NK-cell mediated killing is a major limitation to
      successful allo- and xenotransplantation. The molecular mechanisms that regulate
      the fusion of granzyme B-containing secretory lysosomes to the plasma membrane in
      activated NK cells, prior to target cell killing, are not fully understood. Using
      the NK cell line YT-Indy as a model, we have investigated the expression of SNAP
      REceptors (SNAREs), both target (t-) and vesicular (v-) SNAREs, and their
      function in granzyme B-mediated target cell killing. Our data showed that YT-Indy
      cells express VAMP-7 and SNAP-23, but not VAMP-2. VAMP-7 was associated with
      granzyme B-containing lysosomal granules. Using VAMP-7 small interfering RNA
      (siRNA), we successfully knocked down the expression of VAMP-7 protein in YT-Indy
      to less than 10% of untreated cells in 24h. VAMP7-deficient YT-Indy cells
      activated via co-culture with Jurkat cells released <1ng/mL of granzyme B,
      compared to 1.5-2.5 microg/mL from controls. Using Jurkat cells as targets, we
      showed a 7-fold reduction in NK cell-mediated killing by VAMP-7 deficient YT-Indy
      cells. Our results show that VAMP-7 is a crucial component of granzyme B release
      and target cell killing in the NK cell line YT-Indy. Thus, targeting VAMP-7
      expression specifically with siRNA, following transplantation, may be a viable
      strategy for preventing NK cell-mediated transplant rejection, in vivo.

PMID- 18042465
TI  - Concurrent expression of heme oxygenase-1 and p53 in human retinal pigment
      epithelial cell line.
AB  - Heme oxygenase-1 (HO-1) is a stress-responsive protein that is known to regulate
      cellular functions such as cell proliferation, inflammation, and apoptosis. Here,
      we investigated the effects of HO activity on the expression of p53 in the human
      retinal pigment epithelium (RPE) cell line ARPE-19. Cobalt protoporphyrin (CoPP)
      induced the expression of both HO-1 and p53 without significant toxicity to the
      cells. In addition, the blockage of HO activity with the iron chelator DFO or
      with HO-1 siRNA inhibited the CoPP-induced expression of p53. Similarly, zinc
      protoporphyrin (ZnPP), an inhibitor of HO, suppressed p53 expression in ARPE-19
      cells, although ZnPP increased the level of HO-1 protein while inhibiting HO
      activity. Also, CoPP-induced p53 expression was not affected by the formation of
      reactive oxygen species (ROS). Based on these results, we conclude that HO
      activity is involved in the regulation of p53 expression in a ROS-independent
      mechanism, and also suggest that the expression of p53 in ARPE-19 cells is
      associated with heme metabolites such as biliverdin/bilirubin, carbon monoxide,
      and iron produced by the activity of HO.

PMID- 18042466
TI  - A redox-silent analogue of tocotrienol inhibits hypoxic adaptation of lung cancer
      cells.
AB  - We have previously reported that a redox-silent analogue of alpha-tocotrienol
      (T3), 6-O-carboxypropyl-alpha-tocotrienol (T3E) shows more potential anti
      carcinogenic property than T3 in a lung cancer cell (A549 cell). However, the
      mechanisms by which T3E exerts its potential anti-carcinogenic effect is still
      unclear. As tumor malignancy is associated with hypoxia adaptation, in this
      study, we examined whether T3E could suppress survival and invasion in A549 cells
      under hypoxia. Hypoxia treatment drastically-induced activation of the protein
      tyrosine kinase, Src, and its regulated signaling required for hypoxia adaptation
      of A549 tumor cells. The survival and invasion capacity of the tumor cells under
      hypoxia was suppressed by T3E via the inactivation of Src. More specifically, T3E
      dependent inhibition of Src-induced Akt activation contributed to suppression of
      cell survival under hypoxia, and the reduction of fibrinolytic factors such as
      plasminogen activator-1(PAI-1) via the decrease of hypoxia-inducible factor
      2alpha by T3E led to inhibition of hypoxic invasion. Overall these results
      suggest that T3E suppresses hypoxia adaptation of A549 cells by the inhibition in
      hypoxia-induced activation of Src signaling.

PMID- 18042467
TI  - Membrane trafficking of AQP5 and cAMP dependent phosphorylation in bronchial
      epithelium.
AB  - Phosphorylation pathway has been identified as an important step in membrane
      trafficking for AQP5. We generated stably transfected BEAS-2B human bronchial
      epithelial cells with various over-expression constructs on permeable support. In
      stable cells with wild-type AQP5 and S156A (AQP5 mutant targeting PKA consensus
      sequence), AQP5 expression was predominantly polarized to the apical membrane,
      whereas stable cells with N185D (AQP5 mutant targeting second NPA motif), mainly
      localized to the cytoplasm. Treatment with H89 and/or chlorophenylthio-cAMP (cpt
      cAMP) did not affect membrane expression of AQP5 in any of three stable cells. In
      cells with wild-type AQP5 and N185D, AQP5s were phosphorylated by PKA, while
      phosphorylation of AQP5 was not detected in cells with S156A. These results
      indicate that, in AQP5, serine156 may be phosphorylated by PKA, but membrane
      expression of AQP5 may not be regulated by PKA phosphorylation. We conclude that
      AQP5 membrane targeting can include more than one mechanism besides cAMP
      dependent phosphorylation.

PMID- 18042468
TI  - Molecular characterization reveals that YMR278w encoded protein is environmental
      stress response homologue of Saccharomyces cerevisiae PGM2.
AB  - The uncharacterized ORF YMR278w of Saccharomyces cerevisiae is a member of D
      phosphohexomutase super family, annotated as phosphoribomutase. In order to
      evaluate its functional role, we cloned, over-expressed and purified YMR278w
      protein. The protein product of YMR278w exhibits phosphoglucomutase activity.
      S158T mutant derivative of YMR278w protein lost phosphoglucomutase activity.
      Purified YMR278w protein has higher K(m) for glucose-1-phosphate compared to
      other known phosphoglucomutases. Trehalose content was reduced in YMR278w
      disruptant as compared to the wild type strain. Based on the above results we
      suggest that YMR278w encodes phosphoglucomutase and not phosphoribomutase.

PMID- 18042469
TI  - The multi-functional role of sphingosylphosphorylcholine.
AB  - The sphingomyelin metabolite, sphingosylphosphorylcholine (SPC) has been the
      subject of much recent interest and controversy. Studies have indicated that SPC
      naturally occurs in plasma and a constituent of lipoproteins. Synthesis is also
      increased in some pathological conditions. Research has demonstrated that SPC is
      a potentially important lipid mediator of cell type specific functions in major
      tissues, such as heart, blood vessels, skin, brain and immune system. These
      effects are regulated via a number of different intracellular signalling
      cascades, also dependent upon cell type. Initial reports identifying high
      affinity SPC receptors at first appeared to reinforce the physiological relevance
      of this sphingolipid. However, these studies have now been retracted. Some SPC
      effects have been shown be occur via plasma membrane receptors for the related
      sphingolipid, sphingosine 1-phosphate (S1P). Despite a lack of well-defined
      receptor signal transduction mechanisms and sparse pharmacological data, several
      key characteristics of SPC are now emerging. SPC can act as a mitogen in several
      different cell types and in certain circumstances, may also be a pro-inflammatory
      mediator. In this review, these actions of SPC are discussed with a view to
      understanding the potential physiological relevance of this sphingolipid.

PMID- 18042470
TI  - Optimizing maintenance therapy for chronic obstructive pulmonary disease:
      strategies for improving patient-centered outcomes.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with
      substantial morbidity and mortality. Published practice guidelines and treatment
      algorithms for COPD are designed to increase awareness of the problem and improve
      patient care; however, <40% of subjects diagnosed with COPD are receiving
      appropriate maintenance therapy. OBJECTIVE: This paper reviews the use of
      maintenance therapy in COPD and examines the optimal timing for initiating such
      therapy based on the available literature. METHODS: Relevant publications were
      identified through a search of MEDLINE (1995-May 2007) using the terms COPD,
      guidelines, treatment, maintenance therapy, bronchodilator, ipratropium,
      tiotropium, beta-agonist, salmeterol, and inhaled corticosteroid. English
      language publications discussing pharmacologic maintenance therapy for COPD,
      including practice statements/guidelines, randomized controlled clinical trials,
      systematic reviews, and meta-analyses, with a focus on agents currently approved
      for use in the United States, were selected for inclusion. RESULTS: Although
      guidelines and algorithms agree on the importance of regularly scheduled
      maintenance therapy to reduce symptoms of COPD, minimize activity limitations,
      and improve health status, the timing of the initiation of such therapy is
      debatable. In most instances, maintenance medications, which include long-acting
      beta(2)-agonists, long-acting anticholinergics, and combination products, are
      prescribed late in the disease process and mainly for patients with severe
      disease. However, there is increasing evidence that the use of maintenance
      therapy early in the disease process may be associated with improvements in such
      outcomes as lung function, symptoms, exercise tolerance, exacerbations of COPD,
      and quality of life. CONCLUSION: The high burden associated with COPD highlights
      the need to initiate maintenance therapy before a substantial decline in lung
      function has occurred.

PMID- 18042471
TI  - Evidence-based pharmacologic management of pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a debilitating chronic
      disorder of the pulmonary vasculature characterized by elevated mean pulmonary
      arterial pressure, right-sided heart failure, and early mortality. OBJECTIVES:
      This paper reviews the available information on PAH, including its
      pathophysiology, classification of its severity, current treatment options, drug
      interactions, pharmacokinetics, and cost considerations. The results of clinical
      trials of the available treatments are summarized, and a suggested treatment
      algorithm is provided as a guide to the medical management of PAH. METHODS:
      Pertinent articles were identified by a search of MEDLINE through May 2007 using
      the terms primary pulmonary hypertension, pulmonary arterial hypertension,
      prostacyclin, pulmonary vasodilators, endothelin-receptor antagonists, and
      phosphodiesterase inhibitors. Trials with prospective, randomized designs were
      given precedence, and prospective studies having nonrandomized, open-label
      designs or using historical controls were included if they contributed useful
      knowledge. Retrospective studies were not included. RESULTS: In two 12-week,
      randomized, open-label trials in patients with moderate to severe PAH (N = 81 and
      N = 111), exercise capacity, measured on the 6-minute walk test (6-MWT), was
      significantly improved with intravenous epoprostenol compared with conventional
      therapy (+31 vs -29 m, respectively, in one study [P = 0.002]; +46 vs -48 m in
      the other [P < 0.001]). In one of these trials, intravenous epoprostenol also was
      associated with a significant survival benefit (P < 0.003). In a 12-week,
      randomized, doubleblind, placebo-controlled trial in 470 patients with moderate
      to severe PAH, subcutaneous treprostinil plus conventional therapy was associated
      with a significant improvement on the 6-MWT compared with conventional therapy
      alone (+10 vs 0 m, respectively; P = 0.006). In a 16-week, randomized, double
      blind, placebo-controlled trial in 213 patients with mild to moderate symptoms,
      the oral endothelin-receptor antagonist bosentan was associated with a
      significant improvement on the 6-MWT compared with placebo (+36 vs -8 m,
      respectively; P </= 0.001) and significantly less clinical worsening at 28 weeks
      (9/144 vs 14/69; P = 0.002). In a 12-week, prospective, randomized, double-blind,
      placebo-controlled trial in 277 patients with PAH, sildenafil 20, 40, and 80 mg
      TID were associated with significant improvements on the 6-MWT compared with
      placebo (all, P < 0.001). In a prospective trial in 76 patients with idiopathic
      PAH, the inhaled prostacyclin iloprost was associated with overall survival rates
      of 93%, 79%, 70%, 59%, 59%, and 49% at 3 months and 1, 2, 3, 4, and 5 years,
      respectively. In an early trial in 64 patients receiving highdose calcium channel
      blockers, those who had responded to initial drug challenge (defined as a > 20%
      decrease in pulmonary arterial pressure and pulmonary vascular resistance
      immediately after challenge) had a survival rate of 94% at 1, 3, and 5 years.
      CONCLUSIONS: Patients who respond to an acute trial of a vasodilator may be
      treated with an oral calcium channel blocker, whereas oral therapies such as
      sildenafil and bosentan have been effective in patients with mild to moderate
      symptoms. Infusions of the prostacyclin analogues epoprostenol and treprostinil
      appear to be the treatment of choice for moderate to severe PAH, and agents with
      alternate routes of delivery such as inhaled iloprost may be advantageous in
      adjunctive roles. Future trials that focus on the long-term effects of currently
      available agents, as well as on combination therapy, are needed.

PMID- 18042472
TI  - Deferasirox for transfusion-related iron overload: a clinical review.
AB  - BACKGROUND: Iron is an essential element involved in energy production,
      mitochondrial respiration, and DNA synthesis in the body. Excess iron forms
      insoluble complexes that are deposited in, and cause damage to, internal organs.
      Diseases such as beta-thalassemia and myelodysplastic syndrome that require
      frequent blood transfusions can result in excess iron in the body. The
      traditional therapy for iron overload is overnight infusion of deferoxamine
      multiple nights per week. Deferasirox is a new once-daily oral agent for iron
      overload that was approved by the US Food and Drug Administration in November
      2005. OBJECTIVE: The objective of this article was to review available data on
      deferasirox in the treatment of iron overload, including its mechanism of action,
      pharmacokinetics, clinical efficacy, and tolerability. METHODS: MEDLINE, Iowa
      Drug Information Service, and International Pharmaceutical Abstracts were
      searched for English-language articles published before February 2007. Terms used
      in the search included deferasirox, Exjade, ICL 670, beta-thalassemia, and iron
      overload. Human clinical trials were included in the review; meeting abstracts
      were excluded from the review of clinical studies. RESULTS: The literature search
      identified 5 Phase I/II studies and 1 Phase III study of deferasirox in pediatric
      and adult populations. In the Phase I/II trials, which focused primarily on
      pharmacokinetics and the safety profile, deferasirox was relatively well
      tolerated. Adverse events were primarily gastrointestinal disruptions and skin
      rash (8%), which usually resolved with continued therapy. The Phase III study was
      a multinational, randomized, open-label noninferiority comparison of the effect
      of deferasirox 5 to 30 mg/kg PO once daily and deferoxamine 20 to 60 mg/kg SC per
      day, 5 days per week, on reducing liver iron concentrations over 1 year in 586
      patients with beta-thalassemia and transfusion-related iron overload. The 2
      agents had similar efficacy, although deferasirox was associated with a higher
      incidence of adverse effects. CONCLUSIONS: Deferasirox is the first oral agent
      for the treatment of iron overload in the United States. It appears to be
      effective and well tolerated. However, its long-term efficacy and safety remain
      to be established.

PMID- 18042473
TI  - Cardiac safety profile of nebulized formoterol in adults with COPD: a 12-week,
      multicenter, randomized, double- blind, double-dummy, placebo- and active
      controlled trial.
AB  - BACKGROUND: Recently, there have been concerns about the tolerability of long
      acting (2)-agonists, including possible adverse cardiovascular effects-a
      particular concern in patients with chronic obstructive pulmonary disease (COPD),
      who are at elevated risk for cardiovascular disease. OBJECTIVE: The aim of this
      study was to assess the cardiac safety profile of nebulized formoterol fumarate
      inhalation solution. METHODS: Cardiac safety was assessed as part of a 12-week,
      randomized, double-blind, double-dummy, placebo- and active-controlled trial that
      was conducted at 38 centers across the United States. Male and female patients
      aged >/=40 years with COPD and without other significant disease were enrolled.
      After a 4- to 14-day, single-blind placebo run-in period, patients with COPD were
      randomly assigned to receive formoterol fumarate inhalation solution 20 microg
      BID via nebulizer (FFIS group), formoterol fumarate 12 microg BID via dry powder
      inhaler (FA group), or placebo. Cardiac effects-measured by changes in heart rate
      (HR) and ventricular premature beats; incidence of proarrhythmic events; change
      in corrected QT (QTc) interval; and incidence of maximum mean change in QTc >/=60
      ms-were assessed using 24-hour Holter monitoring at baseline and 12 weeks; 12
      lead electrocardiography at screening and weeks 4, 8, and 12; and patient diary
      cards. RESULTS: A total of 351 patients with COPD were randomized (mean age, 62.8
      years; 56.1% male; mean postbronchodilator forced expiratory volume in 1 second,
      1.5 L). Holter monitoring found no clinically meaningful effects of FFIS or FA
      treatment on mean or maximum HR, ventricular premature beats, or inci dence of
      arrhythmic events compared with placebo. At week 12, mean (SD) changes from
      baseline in mean HR were -0.6 (10.9), +0.1 (11.6), and -1.4 (9.4) bpm in the
      FFIS, FA, and placebo groups, respectively. The incidence of mean maximum changes
      in QTc >/=60 ms at any time during the 12-week treatment period were 1.6%, 1.8%,
      and 1.8% with FFIS, FA, and placebo, respectively. Treatment-emergent cardiac
      adverse events (AEs) occurred in 4.1%, 3.5%, and 4.4% of patients in the FFIS,
      FA, and placebo groups; withdrawals due to possible cardiac AEs occurred in 1
      patient per treatment group. No deaths or serious cardiac AEs occurred during the
      treatment period. CONCLUSION: In this COPD population, no clinically significant
      cardiac effects were found with twicedaily treatment with nebulized formoterol
      fumarate inhalation solution.

PMID- 18042474
TI  - Buprenorphine transdermal delivery system in adults with persistent noncancer
      related pain syndromes who require opioid therapy: a multicenter, 5-week run-in
      and randomized, double-blind maintenance-of-analgesia study.
AB  - OBJECTIVE: This study compared the efficacy and safety profile of buprenorphine
      transdermal delivery system (BTDS) and placebo in subjects with persistent
      noncancer-related pain who required opioid analgesics. METHODS: This was a
      multicenter, double-blind, parallel-group study in adult subjects (age >/=18
      years) with at least a 2-month history of noncancer-related pain for which they
      received oral opioid combination agents. The study employed a maintenance-of
      analgesia, or randomized-withdrawal, design. During a 7- to 21-day open-label run
      in phase, all subjects received BTDS, titrated as needed. Subjects who achieved
      stable pain control and were able to tolerate BTDS in the run-in phase were
      randomly assigned to continue BTDS at the dose achieved during the run-in phase
      or to receive placebo for up to 14 days. Acetaminophen 500-mg tablets were
      provided as escape (rescue) medication. Subjects completed the study on day 14 or
      when they met predefined criteria for ineffective treatment: requiring >1 g of
      acetaminophen as escape medication on any day of the double-blind evaluation
      phase, requiring a change in study drug dose, having difficulty keeping the patch
      affixed, or discontinuing because of ineffective treatment without meeting any of
      the first 3 criteria. The primary efficacy variable was the proportion of
      subjects with ineffective treatment. Secondary efficacy variables were the time
      to ineffective treatment; the proportion of subjects who reached ineffective
      treatment or discontinued for any reason other than ineffective treatment; and
      the amount of escape medication used. Assessment of the safety profile was based
      on adverse events and changes in vital signs and physical and laboratory
      findings. RESULTS: Five hundred eighty-eight subjects entered the open-label run
      in phase, and 267 (129 BTDS, 138 placebo) were subsequently randomized to
      doubleblind treatment. Demographic characteristics were similar between the
      double-blind BTDS and placebo groups (61.2% and 63.8% female, respectively; 99.2%
      and 98.6% white; mean [SD] age, 56.2 [13.3] and 59.2 [11.5] years). In the
      primary efficacy analysis, the proportion of subjects with ineffective treatment
      was lower with BTDS than with placebo (51.2% vs 65.0%; 95% CI, 1.09-2.95); the
      odds of ineffective treatment were 1.79 times greater for placebo relative to
      BTDS (P = 0.022). In the secondary efficacy analyses, the median time from the
      first dose of double-blind study drug to ineffective treatment was significantly
      longer with BTDS than with placebo (median, 10 vs 3 days; P = 0.011). The
      proportion of subjects who reached ineffective treatment or discontinued for
      reasons other than ineffective treatment was lower in the BTDS group compared
      with the placebo group (55.0% vs 67.9%); the odds of ineffective treatment or
      discontinuation for a reason other than ineffective treatment was 1.76 times
      greater with placebo compared with BTDS (P = 0.028). The mean amount of escape
      medication used was significantly lower in the BTDS group than in the placebo
      group (1.7 vs 2.2 acetaminophen tablets per day; P = 0.015). The most common
      adverse events in the open-label run-in or double-blind phase occurring at a
      higher incidence with BTDS than with placebo were pruritus at the patch
      application site (9.3% vs 5.1%, respectively), headache (3.9% vs 2.2%), and
      somnolence (2.3% vs 0.7%). CONCLUSION: In this population of adult subjects with
      persistent noncancer-related pain who required opioid therapy, BTDS use was
      associated with analgesic efficacy and was generally well tolerated. Results of
      this study were presented in part at the annual meeting of the American Pain
      Society, March 30-April 2, 2005, Boston, Massachusetts.

PMID- 18042475
TI  - Pharmacokinetic properties of rosuvastatin after single-dose, oral administration
      in Chinese volunteers: a randomized, open-label, three-way crossover study.
AB  - BACKGROUND: Rosuvastatin, a 3-hydroxy-3-methyl glutaryl coenzyme A reductase
      inhibitor ("statin"), has been marketed for the treatment of patients with
      dyslipidemia. OBJECTIVES: The objective of this study was to assess the dose
      proportionality and pharmacokinetic (PK) properties of rosuvastatin after single
      dose administration in Chinese volunteers. The effects of food and sex on the PK
      properties of rosuvastatin in these volunteers were also assessed. METHODS: This
      single-dose, randomized, open-label, 3-way crossover trial was conducted at West
      China Second University Hospital, Sichuan University, Chengdu, People's Republic
      of China. Healthy, male and female, adult (aged 20-24 years), Han Chinese
      volunteers were enrolled. Volunteers were allocated to receive, in randomized
      order according to a computer-generated randomization schedule, single doses of
      rosuvastatin (5, 10, and 20 mg) administered in separate trial periods, with a 1
      week washout between periods. PK properties (C(max), T(max), AUC(0-t), apparent
      elimination t(1/2)) and tolerability were assessed immediately before (0 hour)
      and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, and 72 hours after
      study drug administration. The Student-Newman-Keuls test was used to test for
      linearity. The effects of food intake and sex on the PK properties of
      rosuvastatin were also investigated in subanalyses using standardized meals and
      the t test of logarithm-transformed (lg) values to detect differences in C(max)
      and AUC(0-t) between sexes and between the fed (test) and fasted (reference)
      states. All of the results were corrected for dose by weight (mg/kg). RESULTS:
      The study enrolled 12 healthy Chinese volunteers (6 men: mean [SD] age, 22.3
      [1.5] years; mean [SD] weight, 61.8 [2.4] kg [range, 59-64 kg]; 6 women: mean
      [SD] age, 21.6 [1.4] years; mean [SD] weight, 56.4 [6.4] kg [range, 50-64 kg]).
      Geometric mean (SD) C(max) values of 10.22 (8.05), 25.86 (18.77), and 44.99
      (17.99) ng/mL were achieved at a median T(max) of 2.5 hours after administration
      of single doses of 5, 10, and 20 mg of rosuvastatin, respectively; the
      corresponding geometric mean (SD) values of AUC(0-t) were 73.67 (48.78), 210.21
      (178.70), and 303.81 (193.29) ng/mL . h(-1), and the mean (SD) apparent
      elimination t(1/2) values were 13.01 (8.68), 13.33 (5.21), and 15.40 (5.43) hours
      after administration. The Student-Newman-Keuls test results found that C(max) and
      AUC(0-t) were both linearly related to dose. In men, the mean (SD) C(max) values
      were 7.57 (6.49), 20.43 (14.10), and 36.80 (15.64) ng/mL, and the mean (SD) AUC(0
      t) values were 51.74 (33.92), 136.35 (97.18), and 232.25 (101.66) ng/mL x h(-1),
      with the 5-, 10-, and 20-mg doses of rosuvastatin, respectively. In women, the
      corresponding C(max) values were 13.40 (9.27), 32.44 (23.10), and 54.82 (16.78)
      ng/mL, and AUC(0-t) values were 99.99 (54.07), 298.85 (223.66), and 430.21
      (194.61) ng/mL x h-1. Results of the t tests of (lg)C(max) and (lg)AUC(0-t) found
      no significant differences between the male and female groups. However, C(max)
      and AUC(0-t) values of 0.82 ng/mL and 6.87 ng/mL x h-1, respectively, after oral
      administration of 10 mg of rosuvastatin in the fed state were significantly
      different from the corresponding values under fasting conditions (both, P <
      0.05). Two adverse events (pharyngitis and nausea) were reported in 3 subjects (2
      women, 1 man) at the 20-mg fasting state. Two cases of elevated laboratory values
      (bilirubin, from 16.1 micromol/L at baseline to 31.4 micromol/L; phosphocreatine,
      from 141 U/L at baseline to 307 U/L) were found at the poststudy follow-up
      immediately after study completion in 2 volunteers (1 man, 1 woman) at the 10-mg
      fed state; both values had returned to normal 5 days later. CONCLUSIONS: The PK
      properties of rosuvastatin are based on first-order kinetics in the dose range
      tested. In this small, selected group of healthy Chinese volunteers, no
      clinically significant differences in PK properties between doses or sexes were
      found. The absorption of rosuvastatin was significantly decreased in the fed
      state compared with the fasting state, which suggests that rosuvastatin should be
      administered on an empty stomach. All rosuvastatin doses tested were well
      tolerated.

PMID- 18042476
TI  - Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic
      acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's
      disease: a 26-week, randomized, double-blind, placebo-controlled study in
      Taiwanese patients.
AB  - BACKGROUND: Elevated serum homocysteine levels have been associated with the
      development of Alzheimer's dementia (AD). The combined use of a mecobalamin
      capsule preparation, which contains vitamin B12 0.5 mg with an active methyl
      base, and an over-the-counter nutritional supplement that contains folic acid 1
      mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering
      vitamin regimen. OBJECTIVE: The aim of this study was to determine whether oral
      multivitamin supplementation containing vitamins B6 and B12 and folic acid would
      improve cognitive function and reduce serum homocysteine levels in patients with
      mild to moderate AD. METHODS: This randomized, double-blind, placebocontrolled
      trial was conducted at En Chu Kong Hospital, Taipei, Taiwan. Male and female
      patients aged >50 years with mild to moderate AD and normal folic acid and
      vitamin B12 concentrations were enrolled. All patients received treatment with an
      acetylcholinesterase inhibitor and were randomized to receive add-on mecobalamin
      (B12) 500 mg + multivitamin supplement, or placebos, PO QD for 26 weeks. The
      multivitamin contained pyridoxine (B6) 5 mg, folic acid 1 mg, and other vitamins
      and iron. Serum homocysteine level was measured and cognitive tests were
      conducted at baseline and after 26 weeks. The primary efficacy outcome was change
      in cognition, measured as the change in score from baseline to week 26 on the
      Alzheimer's Disease Assessment Scale 11-item Cognition subscale. Secondary
      efficacy outcomes included changes in function in performance of activities of
      daily living (ADLs) and concentrations of homocysteine, B12, and folic acid.
      Tolerability was assessed by comparing the 2 study groups with respect to
      physical examination findings, including changes in vital signs, laboratory test
      abnormalities, concomitant medication use, and compliance of study medication was
      assessed using an interview with the patient's caregiver, as well as the
      monitoring of adverse events (AEs) throughout the study. RESULTS: Eighty-nine
      patients (45 men, 44 women; all Taiwanese; mean [SD] age, 75 [7.3] years) were
      enrolled and randomized. Overall, there were no significant differences in
      cognition or ADL function scores between the 2 groups. At week 26, the mean (SD)
      between-group difference in serum homocysteine concentration versus placebo was 
      2.25 (2.85) micromol/L (P = 0.008), and the mean serum concentrations of vitamin
      B12 and folic acid were significantly higher (but within normal range) in the
      multivitamin group compared with placebo (., +536.9 [694.4] pg/mL [P < 0.001] and
      +13.84 ng/mL [11.17] [P = 0.012] at 26 weeks, respectively). The 2 most common
      AEs were muscle pain (11.1% and 6.8%) and insomnia (8.9% and 9.1%) in the
      multivitamin and placebo groups, respectively. CONCLUSIONS: In this population of
      patients with mild to moderate AD in Taiwan, a multivitamin supplement containing
      vitamins B(6) and B(12) and folic acid for 26 weeks decreased homocysteine
      concentrations. No statistically significant beneficial effects on cognition or
      ADL function were found between multivitamin and placebo at 26 weeks.

PMID- 18042477
TI  - Identification and pretherapy susceptibility of pathogens in patients with
      complicated urinary tract infection or acute pyelonephritis enrolled in a
      clinical study in the United States from November 2004 through April 2006.
AB  - OBJECTIVE: The purpose of this study was to assess the pretherapy microbiology
      and fluoroquinolone susceptibility of pathogens from 650 patients with
      complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) as part
      of a multicenter, randomized, controlled clinical trial. METHODS: In this post
      hoc analysis of a multicenter, randomized, double-blind study, adults with a
      clinical diagnosis of cUTI or AP were recruited from 130 community-based and
      institution-based study centers in the United States from November 2004 through
      April 2006. Urine and blood culture specimens were identified and tested for
      susceptibility according to Clinical and Laboratory Standards Institute methods.
      Presence of a pathogen in the urine culture was confirmed by a colony count of
      =105 colony-forming units per milliliter. Susceptibility to nonstudy drugs
      (trimethoprim/sulfamethoxazole [TMP/SMX] and ampicillin) and to study drugs
      (levofloxacin and ciprofloxacin) was categorized as susceptible, intermediate, or
      resistant. RESULTS: Six hundred fifty patients (417 women, 233 men; age range, 18
      94 years) with a diagnosis of cUTI or AP were recruited. A total of 68.2%
      patients (224 men, 219 women) were diagnosed with cUTI, and 31.8% (198 women, 9
      men), with AP. Most (646/650 [99.4%]) infections were community acquired. The
      most common pathogen was Escherichia coli (65.6%), although 12.2% of patients had
      gram-positive pathogens. Testing for susceptibility to ampicillin and TMP/SMX
      found that 50.1% and 22.1% of gramnegative pathogens were fully resistant to
      ampicillin and TMP/SMX, respectively. However, 91.9% of isolates were susceptible
      to levofloxacin and ciprofloxacin, with 6.5% of isolates resistant or
      intermediately resistant to levofloxacin, and 9.7% of isolates resistant or
      intermediately resistant to ciprofloxacin at study entry (P < 0.001 [Stuart
      Maxwell test]). All isolates resistant to levofloxacin were also resistant to
      ciprofloxacin, whereas 6 isolates that were fully susceptible to levofloxacin
      were fully resistant to ciprofloxacin. CONCLUSION: In this study, the level of
      fluoroquinolone susceptibility of urinary pathogens was high (90.6% in cUTI;
      98.1% in AP).

PMID- 18042478
TI  - Abuse potential of carisoprodol: a retrospective review of Idaho Medicaid
      pharmacy and medical claims data.
AB  - BACKGROUND: Carisoprodol is a muscle relaxant indicated as adjunctive therapy in
      acute, painful musculoskeletal conditions. Case reports of drug-seeking behavior
      and utilization of carisoprodol in combination with opioids have suggested abuse
      potential. OBJECTIVES: We undertook a retrospective review of claims data to
      identify and characterize potential indicators of abuse in long-term users of
      carisoprodol and to determine any continued use of the drug by former long-term
      users following prior authorization implementation. METHODS: The Idaho Medicaid
      pharmacy and medical claims database was queried from January 1 to December 31,
      2005, to identify long-term users of muscle relaxants. Use of concomitant opioids
      and coded diagnoses relating to past drug abuse were analyzed and compared
      between patients who used carisoprodol and patients who used other muscle
      relaxants. Data from 11 of 30 surveys mailed to pharmacies filling prescriptions
      for long-term users of carisoprodol were also collected to determine the
      frequency of self-pay-continued use after Medicaid coverage of the drug was
      discontinued. RESULTS: Long-term users of carisoprodol (n = 340) and other
      skeletal muscle relaxants (SMRs) (n = 453) were identified from among 130,000
      individuals in the Idaho Medicaid pharmacy and medical claims database in
      calendar year 2005. Patients in both groups were similar in terms of mean age
      (~47 years) and sex (71.5% female). Patients using carisoprodol used concomitant
      opioids more frequently (81.5% vs 59.8%; P < 0.01), more commonly had past
      diagnoses indicating other drug abuse (34.1% vs 21.4%; P < 0.01), and in 80% of
      reported cases, continued to pay out of pocket for carisoprodol when third-party
      coverage was discontinued. Taken together, these findings are consistent with
      published case reports suggesting the abuse potential of carisoprodol.
      CONCLUSIONS: The results from this review suggest that, compared with long-term
      users of other SMRs, carisoprodol patients utilized concomitant opioids more
      frequently and concomitant NSAIDs less frequently, more commonly had past
      diagnoses indicating other drug dependence or abuse, and continued to pay out of
      pocket for carisoprodol when third-party coverage was discontinued. While none of
      these issues alone may be direct indicators of abuse, collectively they suggest
      that patients who used carisoprodol long term displayed abuse potential
      characteristics more frequently than long-term users of other agents.

PMID- 18042479
TI  - Prospective evaluation of serum amiodarone concentrations when administered via a
      nasogastric tube into the stomach conduit after transthoracic esophagectomy.
AB  - BACKGROUND: Atrial fibrillation occurs in up to 46% of patients following
      esophagectomy; amiodarone may be used for prophylaxis or treatment in these
      patients. There are few data regarding drug absorption following esophagectomy.
      OBJECTIVE: The aim of this study was to determine serum amiodarone concentrations
      when the drug is administered into the stomach conduit following esophagectomy.
      METHODS: Patients who underwent noncardiac thoracic surgery were enrolled in this
      prospective, controlled study. One group of patients underwent esophagectomy, and
      a second group of patients comprised a control group who underwent pulmonary
      resection (PR). A continuous IV amiodarone infusion (0.73 mg/min) was initiated
      at anesthesia induction and continued for 24 hours (total IV dose 1050 mg),
      followed by 400 mg via a nasogastric tube (in the esophagectomy group) or orally
      (in the PR group) every 12 hours for 6 days. Blood samples for determination of
      serum amiodarone concentrations were obtained at completion of the infusion
      (postoperative day [POD] 1), and before the third (POD 2) and seventh (POD 4)
      enteral doses. RESULTS: A total of 27 patients were enrolled (esophagectomy
      group, 13 patients; PR group, 14 patients). Patients in the 2 groups had
      statistically similar ages (mean [SD], 60 [10] vs 53 [10] years; P = 0.07) and
      proportions of men (12/13 [92%] vs 8/14 [57%]; P = 0.08). Patients in the 2
      groups were statistically similar with respect to race (white, 13/13 [100%] vs
      13/14 [93%]) and preoperative weight (mean [SD], 83.3 [11.5] vs 77.7 [18.6] kg).
      On POD 1, age-adjusted and sex-adjusted serum amiodarone concentrations were not
      significantly different in the esophagectomy group versus the PR group (mean [SD]
      0.65 [0.22] vs 0.84 [0.20] microg/mL). Mean (SD) serum amiodarone concentrations
      were significantly lower in the esophagectomy group on POD 2 (0.35 [0.27] vs 0.60
      [0.18] microg/mL; P = 0.02) and on POD 4 (0.30 [0.34] vs 0.87 [0.16] microg/mL; P
      < 0.001). Serum amiodarone concentrations were undetectable in 33% and 50% of
      patients in the esophagectomy group on PODs 2 and 4, respectively, compared with
      0% in the PR group (both, P = 0.03). CONCLUSIONS: Serum amiodarone concentrations
      were significantly lower (and in some cases undetectable) when the drug was
      administered via a nasogastric tube into the stomach conduit in patients after
      esophagectomy compared with those concentrations after oral administration in a
      PR population. Nasogastric administration of amiodarone should probably be
      avoided for prophylaxis or treatment of postesophagectomy tachyarrhythmias.

PMID- 18042480
TI  - The effects of combination treatment with a long-acting beta2-agonist and a
      corticosteroid on salivary flow rate, secretory immunoglobulin A, and oral health
      in children and adolescents with moderate asthma: a 1-month, single-blind
      clinical study.
AB  - BACKGROUND: Asthma is a common chronic disorder of childhood, and it is
      frequently accompanied by dental and other oral abnormalities. As such, oral and
      dental effects of asthma medications have been investigated in several studies.
      However, the effect of combination therapy with a long-acting beta(2)-agonist and
      a corticosteroid on oral health in children and adolescents has not been reported
      in the literature. OBJECTIVE: The aim of this study was to examine whether
      combination treatment with a long-acting beta(2)-agonist (salmeterol) and a
      corticosteroid (fluticasone propionate) administered by dry powder inhaler (DPI)
      affects oral health in children and adolescents with moderate asthma. METHODS:
      This 1-month, single-blind clinical study was conducted at the Department of
      Periodontology, Ondokuz Mayis University Faculty of Dentistry, Samsun, Turkey.
      Male and female children and adolescents aged 7 to 17 years with moderate
      persistent asthma, as classified by the Global Initiative for Asthma guidelines,
      were studied before and after 1 month of treatment with combination salmeterol 50
      microg and fluticasone propionate 100 mug administered by DPI BID. Salivary flow
      rate and secretory immunoglobulin A (sIgA) level were measured, and periodontal
      health was assessed by gingival and dental plaque indices for buccal surfaces and
      periodontal pocket depth. RESULTS: The study enrolled 15 children and adolescents
      (8 girls, 7 boys; mean [SD] age, 11 years [45 months]; median age, 13 years;
      [range, 7-17 years]). At 1 month, mean sIgA, gingival index, buccal surface
      index, gingival index, dental plaque index, and periodontal pocket depth were not
      changed significantly from baseline, whereas mean (SD) salivary flow rate was
      significantly decreased (from 153.21 [39.29] to 113.16 [46.99] microL/5 s; P =
      0.015) and dental plaque index on the buccal surface was significantly increased
      (from 1.43 [0.63] to 1.61 [0.67]; P = 0.01). CONCLUSIONS: In this small study,
      combination treatment with salmeterol 50 microg and fluticasone propionate 100
      microg inhaled twice daily was associated with changes in oral health among these
      children and adolescents with moderate asthma. Regular follow-up of oral health
      status may be warranted in children and adolescents during long-term use of a
      long-acting beta2-agonist and a corticosteroid.

PMID- 18042481
TI  - The prescribing continuum: between prescription and over-the-counter drugs.

PMID- 18042482
TI  - Oseltamivir and the risk of influenza-related complications and hospitalizations
      in patients with diabetes.
AB  - OBJECTIVE: This subgroup analysis of a retrospective cohort study examined, from
      a managed care perspective, the risk of influenza-related complications and
      hospitalizations in patients with diabetes who were prescribed oseltamivir for
      the treatment of influenza and those who were not prescribed antiviral treatment.
      METHODS: Health insurance claims data from the Thomson Healthcare MarketScan
      Research Database for 6 influenza seasons (October 1-March 31) between 2000 and
      2006 were used to identify patients aged >/=18 years with influenza and diabetes.
      Patients who received a prescription for oseltamivir within 1 day of a diagnosis
      of influenza were compared with those who received no antiviral treatment.
      Outcomes included the frequency of pneumonia, respiratory diagnoses, and otitis
      media and its complications, and rates of hospitalization within 14 days of the
      diagnosis of influenza. Cox proportional hazards regression was used to determine
      the relative risk (RR) of influenza-related complications and hospitalizations.
      RESULTS: A total of 9090 patients with diabetes and a diagnosis of influenza were
      identified who met all study criteria. Of these, 2919 (32%) received a
      prescription for oseltamivir and 6171 (68%) received no antiviral treatment.
      Patients receiving oseltamivir had a significant 17% reduction in the risk of
      respiratory illnesses (RR = 0.83; 95% CI, 0.73-0.93) and a 30% reduction in the
      risk of hospitalization for any reason (RR = 0.70; 95% CI, 0.52-0.94). There were
      no significant differences between the oseltamivir and control groups in terms of
      the risks for pneumonia (RR = 0.87; 95% CI, 0.64-1.18), otitis media and its
      complications (RR = 0.96; 95% CI, 0.48-1.91), or hospitalization for pneumonia
      (RR = 0.81; 95% CI, 0.41-1.58). CONCLUSION: In this retrospective study, the risk
      of influenza-associated respiratory illnesses and the number of hospitalizations
      for any reason were reduced in patients with diabetes who were prescribed
      oseltamivir compared with an unmatched group that was not prescribed antiviral
      therapy.

PMID- 18042483
TI  - Cost-effectiveness analysis of bevacizumab combined with chemotherapy for the
      treatment of metastatic colorectal cancer in Japan.
AB  - BACKGROUND: Rapid progress has been made in the treatment of metastatic
      colorectal cancer (mCRC). New treatment regimens for mCRC include not only
      cytotoxic chemotherapy but also targeted monoclonal antibodies, including
      bevacizumab. However, bevacizumab is an expensive medication, which costs from
      300,000 yen to 400,000 yen (US $2500-$3300) per month. OBJECTIVE: The purpose of
      this cost-effectiveness analysis was to examine the economic efficiency of
      treating mCRC with bevacizumab plus chemotherapy versus chemotherapy alone in
      Japan. METHODS: We searched an electronic database (MEDLINE, UpToDate, and
      American Society of Clinical Oncology [ASCO] Virtual Meeting; key terms:
      bevacizumab limited to randomized controlled trial; years: 2000 to present [June
      29, 2007]) to detect randomized controlled trials (RCTs) that compared
      chemotherapy alone with chemotherapy plus bevacizumab. To analyze the cost
      effectiveness of bevacizumab, we used the Weibull regression model and determined
      an expected treatment duration at each state using reported survival curves of
      RCTs. We included only the direct medical costs (2006) of these medications to
      estimate the expected values of incremental costs; thus, the analysis was
      conducted from the perspective of the health care payer. The incremental cost
      effectiveness ratios (ICERs) were calculated from these expected values of
      incremental life-years and incremental costs. RESULTS: We identified 5 articles
      using MEDLINE and 1 trial found on UpToDate and ASCO Virtual Meeting; these data
      composed the final analysis group. First-line chemotherapy regimens included in
      this analysis were bevacizumab + 5-fluorouracil/leucovorin (FU/LV),
      irinotecan/FU/LV (IFL), infusional FU/LV/ oxaliplatin (FOLFOX6), bolus
      FU/LV/oxaliplatin (bFOL), and capecitabine/oxaliplatin (CAPOX). The only second
      line chemotherapy regimen included was FOLFOX4. The ICERs of additional
      bevacizumab when combined with FU/LV,IFL,FOLFOX6, bFOL, and CAPOX were 17.4
      million yen (US $145,000), 11.9 million yen ($99,000), 13.5 million yen
      ($113,000), 16.9 million yen ($141,000), and 8.5 million yen ($71,000),
      respectively, per life-year gained; the ICER was 14.1 million yen ($118,000) with
      second-line FOLFOX4. CONCLUSIONS: In this cost-effectiveness analysis in Japan,
      the ICERs of bevacizumab + FU/LV combination treatment, IFL, and second-line
      FOLFOX4 were high compared with other chemotherapies for mCRC. It remains
      difficult to assess first-line therapies comprising bevacizumab with oxaliplatin
      based regimens, especially CAPOX. Further information is needed to assess cost
      effectiveness.

PMID- 18042484
TI  - An audit of the NICE self-harm guidelines at a local Accident and Emergency
      department in North Wales.
AB  - This paper reports the findings of a self-harm audit based on data collected at
      an A&E department in North Wales. The National Institute for Clinical Excellence
      (NICE) guidelines on the short term physical and psychological management of self
      harm were published in 2004 and the audit was based on technical criteria
      recommended in the guideline booklet, including standards of psychosocial
      assessment, staff training and patient satisfaction information. The data in this
      study related to fifty consecutive self-harm attendances at the A&E department
      Ysbyty Glan Clwyd in the Spring of 2007. The hospital serves a mixed rural/urban
      population of approximately 250,000. Patient satisfaction questionnaires were
      made available to the group subsequently, whilst the staff training audit was
      distributed more widely to include emergency, medicine and mental health
      divisions of the Conwy & Denbighshire NHS Trust. The results demonstrated
      generally high standards of care on psychosocial assessment, though information
      relating to initial ambulance involvement in treatment was often unclear. The
      response to the staff-training questionnaire was an encouraging 44% and indicated
      wide variations between staff groups and areas of work. The patient satisfaction
      returns demonstrated favourable responses, with several comments added to expand
      on tick box replies. Service developments, as a result of the audit, include the
      proposal to provide mental health and self-harm training to all those staff
      likely to encounter the behaviour--not just to those who work in mental health.
      Patients, from the questionnaire, who express a willingness to become part of a
      mental health planning group are now provided details of the patient
      participation involvement (PPI) group, where their experiences can often inform
      service improvement. Meanwhile the case note audit has reinforced the need for a
      practical self-harm pathway which will ensure consistency.

PMID- 18042485
TI  - Role of health insurance coverage in women's access to prescription medicines.
AB  - OBJECTIVE: To examine the effects of health insurance coverage and other factors
      on access to prescription medicines for non-elderly women ages 18-64. METHODS:
      Based on a nationally representative telephone survey of adult women in the
      United States, this study uses multiple logistic regression to determine the
      factors significantly associated with cost barriers among non-elderly women. The
      sample for the study includes 1,177 women ages 18-64 who use >or=1 prescription
      drug on a regular basis. Cost barriers are defined as not filling a prescription
      or skipping or splitting doses owing to cost. A composite variable of income and
      health insurance was created to examine the role of insurance in mitigating
      barriers for women of different income levels. Descriptive analyses report the
      share of subgroups of women who have faced any of these cost barriers, and
      logistic regression analyses were used to examine the role of health insurance,
      income, and other factors in predicting financial access to prescribed
      medications. KEY FINDINGS: Over half (54%) of non-elderly women reported that
      they were taking a prescription medicine on a regular basis, and nearly one third
      (32%) of these women reported experiencing >or=1 affordability barrier in the
      prior year and had to either forgo or delay a prescription and/or reduce dosages
      to make medicines last longer because of costs. Uninsured women had the highest
      odds of facing a cost barrier, regardless of income level. Low-income, uninsured
      women were nearly 7 times as likely to face a cost barrier to prescription drugs,
      compared with higher income women with insurance. Even uninsured women with
      incomes >or=200% of the federal poverty level had 5 times the odds of facing a
      prescription medicine cost barrier, and low-income, insured women experienced 2
      times the odds of a prescription medicine cost barrier, compared with their
      higher income, insured counterparts. CONCLUSION: Lack of health insurance
      coverage was significantly associated with experiencing cost barriers, regardless
      of income level, underscoring the critical role that insurance coverage plays in
      protecting women from out-of-pocket costs and for accessing prescription
      medicines. Limiting out-of-pocket spending is also important for low-income women
      who have insurance, because even minimal costs can act as barriers for this
      group.

PMID- 18042486
TI  - Where do women veterans get their inpatient care?
AB  - PURPOSE: In this study we explore women veterans' use of Veterans Administration
      (VA) and private sector inpatient services. METHODS: Using a comprehensive
      dataset of VA and private hospital admissions, we identified 1,409 female
      patients who were enrolled in the VA system and had an inpatient admission
      between 1998 and 2000 in either the VA or the private sector. For Major
      Diagnostic Categories (MDCs) with >20 admits in each sector, we compared care
      provided in the private sector with care provided in the VA with respect to
      patient characteristics and resource utilization. In addition, we determined
      payment sources for women who used the private sector for inpatient care.
      FINDINGS: Women who used the VA were younger (mean, 54 vs. 60 years; p < .001)
      and more likely to be service connected (39% vs. 24%; p < .001), African American
      (25% vs. 13%; p < .001), and urban dwelling (81% vs. 75%; p < .01). Women
      veterans were significantly more reliant on the VA system for mental diseases,
      alcohol and drug use, and skin/subcutaneous/breast diseases. For every MDC
      examined, VA hospitals had longer mean lengths of stay. Among VA eligible women
      <65 years old using the private sector, 56% used private insurance, 15% used
      Medicare, 14% used Medicaid, and 9% did not have insurance. CONCLUSIONS: In New
      York, female veterans admitted to VA hospitals differed from women admitted to
      private hospitals by patient characteristics, admission reason, and admission
      resource consumption. Many younger women who used the private sector were reliant
      on other government agencies (Medicaid or Medicare) or out-of-pocket payments for
      their inpatient care.

PMID- 18042487
TI  - Re: Case studies of power and control related to tobacco use during pregnancy.

PMID- 18042489
TI  - Modulation of cardiac troponin C function by the cardiac-specific N-terminus of
      troponin I: influence of PKA phosphorylation and involvement in cardiomyopathies.
AB  - The cardiac-specific N-terminus of cardiac troponin I (cTnI) is known to modulate
      the activity of troponin upon phosphorylation with protein kinase A (PKA) by
      decreasing its Ca(2+) affinity and increasing the relaxation rate of the thin
      filament. The molecular details of this modulation have not been elaborated to
      date. We have established that the N-terminus and the switch region of cTnI bind
      to cNTnC [the N-domain of cardiac troponin C (cTnC)] simultaneously and that the
      PKA signal is transferred via the cTnI N-terminus modulating the cNTnC affinity
      toward cTnI(147-163) but not toward Ca(2+). The K(d) of cNTnC for cTnI(147-163)
      was found to be 600 microM in the presence of cTnI(1-29) and 370 microM in the
      presence of cTn1(1-29)PP, which can explain the difference in muscle relaxation
      rates upon the phosphorylation with PKA in experiments with cardiac fibers. In
      the light of newly found mutations in cNTnC that are associated with
      cardiomyopathies, the important role played by the cTnI N-terminus in the
      development of heart disorders emerges. The mutants studied, L29Q (the N-domain
      of cTnC containing mutation L29Q) and E59D/D75Y (the N-domain of cTnC containing
      mutation E59D/D75Y), demonstrated unchanged Ca(2+) affinity per se and in complex
      with the cTnI N-terminus (cTnI(1-29) and cTnI(1-29)PP). The affinity of L29Q and
      E59D/D75Y toward cTnI(147-163) was significantly perturbed, both alone and in
      complex with cTnI(1-29) and cTnI(1-29)PP, which is likely to be responsible for
      the development of malfunctions.

PMID- 18042491
TI  - Panniculectomy concurrent with anterior pelvic exenteration for recurrent
      cervical cancer.
AB  - BACKGROUND: Panniculectomy concurrent with gynecologic cancer surgery is safe and
      facilitates pelvic exposure in the morbidly obese patient. CASE: A 41-year-old
      morbidly obese female is diagnosed with recurrent adenocarcinoma of the cervix
      and has previously been treated with teletherapy and brachytherapy. She undergoes
      an anterior pelvic exenteration for curative intent. CONCLUSION: Panniculectomy
      at the time of pelvic exenteration is feasible. Morbidly obese patients with
      recurrent cervical cancer after treatment with pelvic radiation should be
      considered candidates for curative surgery.

PMID- 18042490
TI  - Novel inhibitor for prolyl tripeptidyl aminopeptidase from Porphyromonas
      gingivalis and details of substrate-recognition mechanism.
AB  - A new inhibitor, H-Ala-Ile-pyrrolidin-2-yl boronic acid, was developed as an
      inhibitor against prolyl tripeptidyl aminopeptidase with a K(i) value of 88.1 nM.
      The structure of the prolyl tripeptidyl aminopeptidase complexed with the
      inhibitor (enzyme-inhibitor complex) was determined at 2.2 A resolution. The
      inhibitor was bound to the active site through a covalent bond between Ser603 and
      the boron atom of the inhibitor. This structure should closely mimic the
      structure of the reaction intermediate between the enzyme and substrate. We
      previously proposed that two glutamate residues, Glu205 and Glu636, are involved
      in the recognition of substrates. In order to clarify the function of these
      glutamate residues in substrate recognition, three mutant enzymes, E205A, E205Q,
      and E636A were generated by site-directed mutagenesis. The E205A mutant was
      expressed as an inclusion body. The E205Q mutant was expressed in soluble form,
      but no activity was detected. Here, the structures of the E636A mutant and its
      complex with the inhibitor were determined. The inhibitor was located at almost
      the same position as in the wild-type enzyme-inhibitor complex. The amino group
      of the inhibitor interacted with Glu205 and the main-chain carbonyl group of
      Gln203. In addition, a water molecule in the place of Glu636 of the wild-type
      enzyme interacted with the amino group of the inhibitor. This water molecule was
      located near the position of Glu636 in the wild-type and formed a hydrogen bond
      with Gln203. The k(cat)/K(M) values of the E636A mutant toward the two substrates
      used were smaller than those of the wild-type by two orders of magnitude. The
      K(i) value of our inhibitor for the E636A mutant was 48.8 microM, which was 554
      fold higher than that against the wild-type enzyme. Consequently, it was
      concluded that Glu205 and Glu636 are significant residues for the N-terminal
      recognition of a substrate.

PMID- 18042492
TI  - Glutamate in dopamine neurons: synaptic versus diffuse transmission.
AB  - There is solid electron microscopic data demonstrating the existence of dopamine
      (DA) axon terminals (varicosities) with or without synaptic membrane
      specializations (junctional complexes) in many parts of the CNS, and notably in
      neostriatum and nucleus accumbens. The dual morphological character of these DA
      innervations has led to the suggestion that the meso-telencephalic DA system
      operates by diffuse (or volume) as well as by classical synaptic transmission. In
      the last decade, electrophysiological and neurochemical evidence has also
      accumulated indicating that monoamine neurons in various parts of the CNS, and
      particularly the mesencephalic DA neurons, might release glutamate as a co
      transmitter. Following the identification of the vesicular transporters for
      glutamate (VGluT), in situ hybridization and RT-PCR studies carried out on
      isolated neurons or standard tissue cultures, and more recently in vivo, have
      shown that VGluT2 mRNA may be expressed in a significant proportion of
      mesencephalic DA neurons, at least in the ventral tegmental area. A current study
      also suggests that the co-expression of tyrosine hydroxylase (TH) and VGluT2 by
      these neurons is regulated during embryonic development, and may be derepressed
      or reactivated postnatally following their partial destruction by neonatal
      administration of 6-hydroxydopamine (6-OHDA). In both 15 day-old and adult rats
      subjected or not to the neonatal 6-OHDA lesion, concurrent electron microscopic
      examination of the nucleus accumbens after dual immunocytochemical labeling for
      TH and VGluT2 reveals the co-existence of the two proteins in a significant
      proportion of these axon terminals. Moreover, all TH varicosities which co
      localize VGluT2 are synaptic, as if there was a link between the potential of DA
      axon terminals to release glutamate and their establishment of synaptic
      junctions. Together with the RT-PCR and in situ hybridization data demonstrating
      the co-localization of TH and VGluT2 mRNA in mesencephalic neurons of the VTA,
      these observations raise a number of fundamental questions regarding the
      functioning of the meso-telencephalic DA system in healthy or diseased brain.

PMID- 18042493
TI  - Plasticity of interneuronal networks of the functionally isolated human spinal
      cord.
AB  - The loss of walking after human spinal cord injury has been attributed to the
      dominance of supraspinal over spinal mechanisms. The evidence for central pattern
      generation in humans is limited due to the inability to conclusively isolate the
      circuitry from descending and afferent input. However, studying individuals
      following spinal cord injury with no detectable influence on spinal networks from
      supraspinal centers can provide insight to their interaction with afferent input.
      The focus of this article is on the interaction of sensory input with human
      spinal networks in the generation of locomotor patterns. The functionally
      isolated human spinal cord has the capacity to generate locomotor patterns with
      appropriate afferent input. Locomotor Training is a rehabilitative strategy that
      has evolved from animal and humans studies focused on the neural plasticity of
      the spinal cord and has been successful for many people with acute and chronic
      incomplete spinal cord injury. However, even those individuals with clinically
      complete spinal cord injury that generate appropriate locomotor patterns during
      stepping with assistance on a treadmill with body weight support cannot sustain
      overground walking. This suggests that although a significant control of
      locomotion can occur at the level of spinal interneuronal networks the level of
      sustainable excitability of these circuits is still compromised. Future studies
      should focus on approaches to increase the central state of excitability and may
      include neural repair strategies, pharmacological interventions or epidural
      stimulation in combination with Locomotor Training.

PMID- 18042494
TI  - Partial volume corrected image derived input functions for dynamic PET brain
      studies: methodology and validation for [11C]flumazenil.
AB  - Extraction of arterial input functions from dynamic brain scans may obviate the
      need for arterial sampling and would increase the clinical applicability of
      quantitative PET studies. The aim of the present study was to evaluate
      applicability and accuracy of image derived input functions (IDIFs) following
      reconstruction based partial volume correction (PVC). Settings for the PVC
      ordered subset expectation maximization (PVC-OSEM) reconstruction algorithm were
      varied. In addition, different methods for defining arterial regions of interest
      (ROI) in order to extract IDIFs were evaluated. [(11)C]flumazenil data of 10
      subjects were used in the present study. Results obtained with IDIFs were
      compared with those using standard on-line measured arterial input functions.
      These included areas under the curve (AUC) for peak (1-2 min) and tail (2-60
      min), volume of distribution (V(T)) obtained using Logan analysis, and V(T) and
      K(1) obtained with a basis function implementation of a single tissue compartment
      model. Best results were obtained with PVC-OSEM using 4 iterations and 16
      subsets. Based on (11)C point source measurements, a 4.5 mm FWHM (full width at
      half maximum) resolution kernel was used to correct for partial volume effects. A
      ROI consisting of the four hottest pixels per plane (over the carotid arteries)
      was the best method to extract IDIFs. Excellent peak AUC ratios (0.99+/-0.09)
      between IDIF and blood sampler input function (BSIF) were found. Furthermore,
      extracted IDIFs provided V(T) and K(1) values that were very similar to those
      obtained using BSIFs. The proposed method appears to be suitable for analysing
      [(11)C]flumazenil data without the need for online arterial sampling.

PMID- 18042495
TI  - Automatic independent component labeling for artifact removal in fMRI.
AB  - Blood oxygenation level dependent (BOLD) signals in functional magnetic resonance
      imaging (fMRI) are often small compared to the level of noise in the data. The
      sources of noise are numerous including different kinds of motion artifacts and
      physiological noise with complex patterns. This complicates the statistical
      analysis of the fMRI data. In this study, we propose an automatic method to
      reduce fMRI artifacts based on independent component analysis (ICA). We trained a
      supervised classifier to distinguish between independent components relating to a
      potentially task-related signal and independent components clearly relating to
      structured noise. After the components had been classified as either signal or
      noise, a denoised fMR time-series was reconstructed based only on the independent
      components classified as potentially task-related. The classifier was a novel
      global (fixed structure) decision tree trained in a Neyman-Pearson (NP)
      framework, which allowed the shape of the decision regions to be controlled
      effectively. Additionally, the conservativeness of the classifier could be tuned
      by modifying the NP threshold. The classifier was tested against the component
      classifications by an expert with the data from a category learning task. The
      test set as well as the expert were different from the data used for classifier
      training and the expert labeling the training set. The misclassification rate was
      between 0.2 and 0.3 for both the event-related and blocked designs and it was
      consistent among variety of different NP thresholds. The effects of denoising on
      the group-level statistical analyses were as expected: The denoising generally
      decreased Z-scores in the white matter, where extreme Z-values can be expected to
      reflect artifacts. A similar but weaker decrease in Z-scores was observed in the
      gray matter on average. These two observations suggest that denoising was likely
      to reduce artifacts from gray matter and could be useful to improve the detection
      of activations. We conclude that automatic ICA-based denoising offers a
      potentially useful approach to improve the quality of fMRI data and consequently
      increase the accuracy of the statistical analysis of these data.

PMID- 18042496
TI  - Composite voxel-based analysis of volume and T2 relaxometry in temporal lobe
      epilepsy.
AB  - Voxel-based analyses of tissue characteristics such as volume and T2 are usually
      carried out in isolation. However, as the images are analysed in a common voxel
      based framework, it is possible to directly assess the spatial relationships of
      abnormalities detected by each technique. We utilize this approach in well
      characterized patients with unilateral temporal lobe epilepsy (TLE) with
      hippocampal sclerosis (HS). TLE is associated with potentially widespread volume
      and T2 signal abnormalities in MRI images but the relationship between these two
      aspects of tissue abnormality is not well understood. Here we use a novel
      approach of combined univariate and multivariate voxel-wise analysis to
      investigate the spatial relationship of these abnormalities. We studied 19 TLE
      patients and compared them to 115 control subjects. Grey matter (GM) and white
      matter (WM) volume changes were assessed with voxel-based morphometry (VBM), and
      changes in T2 relaxation times were evaluated with voxel-based relaxometry (VBR).
      The volume and T2 changes obtained using the combined univariate approach were
      found in an extensive area, prominently in the ipsilateral hippocampus and
      amygdala (overlap of GM-VBM and VBR), and in the remaining temporal lobe (overlap
      of WM-VBR and VBR). Other cortical and subcortical areas showed isolated volume
      or T2 changes. The multivariate analysis based on the Hotelling T(2) statistic,
      indicated a similar pattern of distributed changes across the brain but with a
      greater degree of statistical significance in certain areas. The composite
      analyses appear to identify a network of affected areas not as easily appreciated
      by the individual analysis of volume or T2 changes.

PMID- 18042497
TI  - Radical surgery for hilar cholangiocarcinoma.
AB  - In the therapy of hilar cholangiocarcinoma, the most favorable survival rates
      over the long-term are achieved by a surgical concept involving a no-touch
      technique, en-bloc-resection and wide tumor-free margins. Currently, these goals
      can be best achieved by our strategy to combine extended right hepatic resections
      and principle portal vein resection. In spite of extending resectability to
      patients with locally advanced tumors, formally curative resections could be
      performed in 80% of the patients. The 5-year survival rate in these patients is
      61%. Liver transplantation had been abandoned by most centers in the 1980s due to
      poor overall results. Recently, a neoadjuvant strategy involving
      radiochemotherapy has been reported to result in excellent survival figures at
      least in a subset of patients suffering from cholangiocellular carcinoma arising
      in a primary sclerosing cholangitis (PSC). This protocol has been mainly proposed
      by the Mayo Clinic group and reached 5-year survival rates of 80% in those
      patients in whom it had been applicable. A substantial drop out rate from this
      neoadjuvant regimen due to tumor progression or treatment related complications
      is still a problem.

PMID- 18042498
TI  - Clear cell sarcoma (melanoma of soft parts): The Royal Marsden Hospital
      experience.
AB  - INTRODUCTION: Clear cell sarcoma (CCS) is a rare tumour with a propensity for
      local recurrence and nodal metastasis. About 300 cases have been reported, thus
      further clarification regarding the course and outcome of the disease is
      required. METHODS: Patients with a histopathologic diagnosis of CCS were
      identified from prospective histopathology and sarcoma databases and supplemented
      with a retrospective analysis of the patients' hospital records. RESULTS: Between
      1990 and 2005, a total of 72 patients with a diagnosis of CCS were identified, 35
      having been referred for management and 37 having been referred for
      histopathologic opinion. The median age was 39 years (range 5-90 years). Of the
      35 patients referred to the Royal Marsden Hospital for management, 23% developed
      local recurrence or in-transit metastases at a median of 9 months (2-79 months)
      after resection of the primary, and nodal or distant metastatic disease was seen
      in 63% after 14 months (range 0-177 months). Five- and 10-year survival were 52%
      and 25%, respectively. CONCLUSIONS: CCS has a number of similarities with
      melanoma, particularly in its peripheral distribution and propensity for nodal
      disease. Wide excision with clear margins offers the best chance of cure. Local
      recurrence and regional metastases are common, and are almost always followed by
      distant metastases and death.

PMID- 18042499
TI  - Image-guided craniotomy for frontal sinus preservation during meningioma surgery.
AB  - OBJECTIVE: Preservation of the frontal sinus (FS) during the frontolateral
      approach to the skull base reduces morbidity, enhances patient comfort, and
      speeds up the surgical procedure. Due to its irregular outline, mental
      reconstruction of the borders of FS from two-dimensional images is challenging
      during surgery. This study was designed to evaluate the impact of neuronavigation
      on identification and preservation of the FS during frontolateral craniotomies.
      METHODS: Forty-five patients with pathologies located in the anterior skull base
      and in the parasellar region were included. A standard computed tomography (CT)
      sequence was obtained from each patient and uploaded onto an image-guidance
      system for volumetric rendering of 3D images. The outline of the FS was
      visualized and the distance between its lateral border and the mid-pupillary line
      (MPL) was measured. The results were used for navigated craniotomies and compared
      to the intra-operative findings. RESULTS: The FS was located medial, on and
      lateral to the MPL in 32, 4 and 9 cases, respectively. The individual outline of
      the FS could be identified with a mean target registration error of 1.4mm (+/-0.7
      mm). The craniotomy could be custom-tailored for each patient according to the
      individualized landmarks while visualizing the lesion and the surgical landmarks
      simultaneously. Unintended opening of the frontal sinus or orbit did not occur in
      any of these cases. CONCLUSION: Image-guided craniotomies based on 3D volumetric
      image rendering allow for fast and reliable demarcation of complex anatomical
      structures hidden from direct view in frontolateral approaches. The outline of
      the frontal sinus and the orbit can be appraised at a glance providing additional
      safety and precision during craniotomy.

PMID- 18042500
TI  - Radiofrequency hepatic ablation with internally cooled electrodes and hybrid
      applicators with distant saline infusion using an in vivo porcine model.
AB  - AIMS: Radiofrequency ablation (RFA) of tumors by means of internally cooled (ICE)
      or multitined expandable electrodes combined with infusion of saline into the
      tissue may improve results. Our aim was to determine the efficacy of a previously
      optimized hybrid ICE system (ICE combined with infusion of saline into the tissue
      at a distance of 2mm) in comparison with a conventional ICE cluster electrode in
      porcine liver in vivo. METHODS: A total of 32 RFA were performed on a total of 10
      farm pigs using two RFA systems: Group A (n=16): Cluster electrode. Group B
      (n=16): Hybrid system (with continuous infusion of 100ml/h of 20% NaCl at 2mm
      distance from the electrode shaft by an independent isolated needle). Livers were
      removed for macroscopic and histological assessment after the procedure.
      Coagulation volume, coagulation diameters, coefficient of variability (CV) of
      coagulation volume, sphericity ratio (SR), deposited power (DP), deposited energy
      (DE), deposited energy per coagulation volume (DEV) and rise of animal
      temperature during the procedure were compared and correlated among groups.
      Additionally, linear regression analysis was modeled to study the relationship
      between deposited energy and either coagulation volume and rise of animal
      temperature during the procedure in both groups. RESULTS: Both coagulation volume
      and short diameter of coagulation were significantly greater (p<0.05) in group B
      compared to group A (22.7+/-11.0 cm(3) and 3.1+/-0.7 cm vs. 13.5+/-7.7 cm(3) and
      2.5+/-0.5 cm, respectively). A similar CV and SR was observed among groups (57.1%
      and 1.4+/-0.3 vs. 48.6% and 1.3+/-0.2 for groups B and A, respectively). In group
      B, DE and DP were more than double group A, but DEV was nearly twice as high
      (9782 J/cm(3) vs. 5342 J/cm(3), for groups B and A, respectively). No significant
      relationship between DE and coagulation volume was encountered. CONCLUSION:
      Efficacy of a single ICE may be improved with continuous infusion of saline at
      around 2 mm from the electrode shaft. Coagulation volume obtained with this
      improved system may be even greater than that obtained with a cluster electrode.

PMID- 18042501
TI  - The Incidence of HIV drug resistance and its impact on progression of HIV disease
      among antiretroviral-naive participants started on three different antiretroviral
      therapy strategies.
AB  - BACKGROUND: Treatment-naive participants were randomized to three antiretroviral
      strategies (all with nucleoside reverse transcriptase inhibitor [NRTI]
      background): protease inhibitor (PI), non-nucleoside reverse transcriptase
      inhibitor (NNRTI), or PI+NNRTI. The strategies were compared for drug resistance
      at first virologic failure (VF; HIV RNA >1000 copies/mL). The impact of
      resistance on AIDS or death was determined. METHOD: Drug resistance was
      determined by genotype. Cox models were used to compare the strategies for VF
      with resistance and to determine the impact of resistance on AIDS or death.
      RESULTS: Of 1,360 participants, 866 experienced VF; 226 experienced AIDS or death
      (median follow-up 5 years). Rates (per 100 personyears) for VF with resistance
      were 14.9 (PI), 10.8 (NNRTI), and 11.5 (PI+NNRTI); hazard ratio (HR) was 0.78
      (95% CI 0.61-0.99) for NNRTI versus PI. Compared to those with no VF, there was a
      significantly increased risk of AIDS or death for participants with solitary
      NNRTI resistance (HR 2.31, 95% CI 1.46-3.66) and for those failing with no known
      resistance (HR 1.78, 95% CI 1.18-2.68). Participants failing with solitary NNRTI
      resistance and with no resistance had the lowest percent of time on
      antiretroviral treatment (ART) and the lowest cumulative mean adherence scores.
      CONCLUSION: For treatment-naive participants, the risk of AIDS or death is
      increased for those who failed virologically with solitary NNRTI resistance and
      those who failed with no known drug resistance compared to those with no
      virologic failure. Both the lack of ART exposure in nonadherent participants and
      the development of NNRTI resistance among those who take and fail their ART
      regimen predict poor clinical outcomes.

PMID- 18042502
TI  - Evaluation of sex differences of fosamprenavir (with and without ritonavir) in
      HIV-infected men and women.
AB  - PURPOSE: Recent studies focusing on HIV-1-infected women have suggested the
      existence of sex-related differences in natural history, antiretroviral
      pharmacokinetics, efficacy, and tolerability. This article analyzes three pivotal
      trials of the protease inhibitor (PI) fosamprenavir (FPV) with a view to
      providing a better understanding of potential sex differences in efficacy and
      safety. METHOD: A post hoc, descriptive analysis was performed on data from 700
      subjects (26% women) in three trials of FPV to evaluate sex differences with
      regard to efficacy, rates of discontinuation, and treatment-related adverse
      events. RESULTS: No major sex differences were found. Men and women had similarly
      good antiviral responses, with greater than 60% of treatment-naive subjects
      achieving virologic suppression (<400 copies/mL) at 48 weeks. PI-experienced
      women in CONTEXT receiving once-daily FPV/r experienced the highest rates of
      discontinuations due to virologic failure (29% in women vs. 8% in men). Women
      generally had slightly lower rates of liver enzyme elevations and fewer
      abnormalities of total cholesterol and triglycerides. CONCLUSION: The absence of
      major sex differences provides reassurance, but the small number of women in
      these trials limited the ability to draw conclusions. Future trials should be
      specifically powered to detect sex differences in safety and efficacy.

PMID- 18042503
TI  - The safety and efficacy of switching stavudine to tenofovir df in combination
      with lamivudine and efavirenz in hiv-1-infected patients: three-year follow-up
      after switching therapy.
AB  - BACKGROUND: Study 903 is a phase 3 trial with a completed 144-week, double-blind
      phase comparing tenofovir DF (TDF) with stavudine (d4T), in combination with
      lamivudine (3TC) and efavirenz (EFV), and an ongoing 336-week open-label
      extension phase. METHOD: Patients in 3 countries completing the d4T treatment
      phase were allowed to switch d4T to TDF and receive once-daily TDF+3TC+EFV in the
      extension phase. RESULTS: At the time of switch, 100% and 99% of patients (n =
      85; 60% male, 64% White; mean age 37 years; mean CD4 = 650 cells/mm3) had HIV RNA
      <400 and <50 copies/mL. At 144 weeks after the switch, 89% (missing = failure)
      had HIV RNA <400 copies/mL and 87% had HIV RNA <50 copies/mL. Mean CD4 cell count
      increased 155 cells/mm3. No patient had virologic failure. Significant decreases
      from switch to week 144 in mean fasting total cholesterol (-22 mg/dL, p < .0001)
      and triglycerides (-78 mg/dL, p < .0001) were observed. Mean limb fat increased
      significantly from 4.5 kg to 5.8 kg, 144 weeks after switch (p < .0001).
      CONCLUSION: In virologically suppressed patients, switching d4T to TDF as part of
      a once-daily regimen with 3TC and EFV resulted in maintenance of virologic
      suppression and continued CD4 cell increases through 144 weeks, with significant
      improvements in metabolic parameters.

PMID- 18042504
TI  - Case-control exploration of relationships between early rash or liver toxicity
      and plasma concentrations of nevirapine and primary metabolites.
AB  - OBJECTIVE: This investigation measured trough nevirapine and five oxidative
      metabolite concentrations in plasma specimens collected from patients who
      exhibited a rash or liver function abnormality during the first 6 weeks of
      treatment. METHOD: Patient selection came from three clinical trials, totaling
      1,357 patients, from which frozen specimens had been stored and were available
      for assay. The control patients were matched according to trial, steroid use, CD4
      cell count, gender, race, and hepatitis B/C status. Observed plasma metabolite
      concentrations were compared using signed rank tests. RESULTS: A total of 49 case
      control pairs were studied. Women had significantly greater exposure than men to
      nevirapine and four of the five metabolites at week 2, but the plasma
      concentrations were comparable by week 4. Steroid (prednisone) co-medication
      produced significantly different plasma nevirapine and metabolite concentrations
      for the majority of case-control comparisons at week 3, a week after cessation of
      steroid treatment, but only occasionally produced a measurable difference at
      other weeks. CONCLUSION: During the first 6 weeks of nevirapine therapy, the
      rashes and liver enzyme elevations that occurred appear to be idiosyncratic.
      There were no strong relationships observed between the plasma concentrations of
      nevirapine or any of its five metabolites to a casedefining event. The systemic
      exposure of the metabolite 12-hydroxynevirapine and its successor 4
      carboxynevirapine, hypothesized in the skin rash female Brown Norway rat model as
      reactive intermediates for idiosyncratic immune-mediated adverse reactions, were
      comparable between case and control samples and were comparable in proportion to
      the precursor nevirapine exposure.

PMID- 18042505
TI  - Effectiveness and tolerability of oral administration of low-dose salmon oil to
      HIV patients with HAART-associated dyslipidemia.
AB  - PURPOSE: To assess the effectiveness of low-dose salmon oil for the treatment of
      highly active antiretroviral therapy (HAART)-induced dyslipidemia in HIV-infected
      patients. METHOD: Randomized, open-label, parallel and crossover, multicenter
      study. Patients received 1 g salmon oil tid for 24 weeks (SO-24) or no additional
      treatment for 12 weeks and salmon oil for weeks 12 to 24 (CT-SO). The primary
      outcome measure was the change in triglyceride (TG) levels. RESULTS: Fifty-eight
      patients completed the study (26 in SO-24; 32 in CT-SO). After 12 weeks, the SO
      24 group experienced a mean TG reduction of 1.1 mmol/L, compared to an increase
      of 0.3 mmol/L for the CT-SO group (p = .040). When CT-SO patients were crossed
      over to salmon oil treatment, mean TG decreased by 0.7 mmol/L (p = .052).
      Concomitant use of fibrates, statins, or both were reported by 16 (27.6%), 10
      (17.2%), and 8 (13.8%), respectively. Multivariate analysis showed that salmon
      oil produced a significant decrease in TG levels independent of other lipid
      lowering medications (p = .022). There were 26 predominately mild treatment
      emergent (antiretroviral or salmon oil) nonserious adverse events reported by 22
      (33.3%) patients. CONCLUSION: Low-dose salmon oil (3 g/day) is effective and well
      tolerated in reducing TG levels in HIV-infected patients receiving HAART.

PMID- 18042506
TI  - Prospective study of topical testosterone gel (AndroGel) versus intramuscular
      testosterone in testosterone-deficient HIV-infected men.
AB  - PURPOSE: Testosterone replacement therapy via deep intramuscular injections
      causes extraphysiologic variations in serum testosterone concentrations. A
      topical transdermal testosterone gel formulation (AndroGel(R)) provides sustained
      physiologic concentrations of serum testosterone. The objective of this open
      label switch study was to compare pharmacokinetics, safety, tolerability, and
      efficacy of delivery of daily testosterone gel versus intramuscular testosterone
      injection every 1 or 2 weeks in hypogonadal human immunodeficiency virus (HIV)
      infected men. METHOD: Patients received intramuscular testosterone (100-200
      mg/wk) for 8 weeks, then switched to daily topical testosterone gel (5-10 g
      gel/day) for 8 weeks. Study endpoints included free serum testosterone
      concentrations and quality-of-life scores. RESULTS: Thirty patients (average age,
      45 years) were recruited; 24 completed the study. Mean peak free testosterone
      concentrations with intramuscular testosterone and testosterone gel were 42 pg/mL
      and 23 pg/mL, respectively, and mean peaktrough fluctuations in free testosterone
      were 26.7 +/- 12.8 pg/mL and 2.7 +/- 10.7 pg/mL, respectively (p < .001). Quality
      of-life scores indicated more improved physical and emotional well-being with gel
      versus intramuscular testosterone. No significant changes in laboratory
      parameters or lean body mass were noted. CONCLUSION: Daily testosterone gel
      produced stable testosterone concentrations and improved quality of life compared
      with intermittent intramuscular testosterone injections.

PMID- 18042507
TI  - Evaluation of Stool frequency and stool form as measures of HIV-related diarrhea.
AB  - PURPOSE: In the highly active antiretroviral therapy (HAART) era, HIV-related
      diarrhea remains common. Our aim was to evaluate stool frequency and form as
      measures of HIV-related diarrhea. METHOD: Forty-eight HIV-infected persons with
      self-reported diarrhea were studied. In Analysis 1, self-reported retrospective
      and 7-day prospective measurement of stool frequency and form were compared using
      Spearman's correlation coefficient. In Analysis 2, diarrhea was measured during
      two 8-hour study periods in a subgroup (n = 20) using stool weight (Wt), diarrhea
      symptom score (Sx Score), stool frequency (SP-freq), and stool form using the
      Bristol Stool Form Scale (SP-BSFS). SP-freq and SP-BSFS were modeled alone and in
      combination to predict Wt and Sx Score. RESULTS: In Analysis 1, correlation
      between measures of stool frequency was rs = 0.62 (p < .0001) but was rs = 0.16
      (p = .26) between measures of stool form. In Analysis 2, the two-predictor model
      best predicted Wt, whereas the model using SP-freq only performed as well as the
      two-predictor model to predict Sx Score. CONCLUSION: Prospective measurement of
      stool frequency performed well; in some situations, it may be used alone to
      measure severity of HIV-related diarrhea. Our findings may be used to design more
      rigorous clinical trials in HIV.

PMID- 18042508
TI  - Effect of antiretroviral therapy and hepatitis c co-infection on changes in lipid
      levels in HIV-Infected patients 48 weeks after initiation of therapy.
AB  - Hepatitis C virus (HCV) commonly co-infects HIV-infected individuals.
      Antiretroviral therapy (ART) is associated with elevated serum lipid levels, and
      HCV infection is associated with low serum lipid levels. Fasting lipid levels
      were investigated in 1,434 ART-naive HIV-infected people participating in the
      AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT)
      protocol who prospectively initiated ART with 3 agents. Subjects with elevated
      liver-associated enzymes (>5 x ULN) were excluded. Demographics, body mass index,
      HCV status, CD4 cell count, HIV RNA, liver enzymes, lipid levels, and glucose
      were assessed before and following 48 weeks of ART. HCV-positive subjects (n =
      160; 11%) were older, more likely to be Black, have a history of intravenous drug
      use (IDU), have higher baseline liver-associated enzyme levels than the HCV
      negative group (p < .001 for each), and to have diabetes at baseline (5% vs. 2%,
      p = .07). Lipid levels rose in both groups following ART, and the differences
      were not significant except that HDL levels increased significantly more in the
      HCV-positive group (p = .006). In summary, HCV infection did not appear to
      provide significant protection against ART-induced hyperlipidemia in this cohort
      of HIV-infected subjects prospectively enrolled in ART trials, although HDL
      levels rose to a greater degree.

PMID- 18042509
TI  - Selegiline transdermal system (STS) for HIV-associated cognitive impairment: open
      label report of ACTG 5090.
AB  - OBJECTIVE: To assess the long-term safety (primary aim) and efficacy (secondary
      aim) of the MAO-B inhibitor Selegiline Transdermal System (STS) for the treatment
      of HIV-associated cognitive impairment. BACKGROUND: HIV infection is associated
      with increased oxidative stress. In vitro and animal studies have shown that
      selegiline can reduce oxidative stress levels while enhancing the synthesis of
      neurotrophic factors. We conducted and reported a 24-week, double-blind, placebo
      controlled study with STS in HIV-infected individuals with cognitive impairment
      (ACTG 5090). We now report the results of the 24-week open-label follow-up.
      METHOD: Subjects received either 3 mg/24 h or 6 mg/24 h STS daily. The primary
      efficacy endpoint was changes in the mean of z scores of six neuropsychological
      tests (NPZ-6). Additional outcomes included NPZ-8 and NPZ scores by cognitive
      domain. RESULTS: 86 subjects were enrolled. There were few severe adverse
      experiences (n = 13). There was no significant change in NPZ-6 score, whereas
      significant changes were observed in NPZ-8 score and several cognitive domains.
      CONCLUSION: Long-term use of selegiline was safe and well tolerated in this HIV
      cohort of HIV with cognitive impairment. Cognitive improvement may be delayed in
      neuroprotective trials, suggesting that trials longer than 6 months may be
      necessary to assess the efficacy of putative neuroprotective agents.

PMID- 18042510
TI  - Temperature-related birth sex ratio bias in historical Sami: warm years bring
      more sons.
AB  - The birth sex ratio of vertebrates with chromosomal sex determination has been
      shown to respond to environmental variability, such as temperature. However, in
      humans the few previous studies on environmental temperature and birth sex ratios
      have produced mixed results. We examined whether reconstructed annual mean
      temperatures were associated with annual offspring sex ratio at birth in the
      eighteenth to nineteenth century Sami from northern Finland. We found that warm
      years correlated with a male-biased sex ratio, whereas a warm previous year
      skewed sex ratio towards females. The net effect of one degree Celsius increase
      in mean temperature during these 2 years corresponded to approximately 1% more
      sons born annually. Although the physiological and ecological mechanisms
      mediating these effects and their evolutionary consequences on parental fitness
      remain unknown, our results show that environmental temperature may affect human
      birth sex ratio.

PMID- 18042511
TI  - Aggressive and non-aggressive personalities differ in oxidative status in
      selected lines of mice (Mus musculus).
AB  - Mice selected for aggression and coping (long attack latency (LAL), reactive
      coping strategy; short attack latency (SAL), pro-active coping strategy) are a
      useful model for studying the physiological background of animal personalities.
      These mice also show a differential stress responsiveness, especially in terms of
      hypothalamic-pituitary-adrenal axis reactivity, to various challenges. Since the
      stress response can increase the production of reactive oxygen species, we
      predicted that the basic oxidative status of the lines could differ. We found
      that LAL showed higher serum antioxidant capacity (OXY) than SAL, while no
      differences emerged for reactive oxygen metabolites (ROMs) or the balance between
      ROMs and OXY, reflecting oxidative stress. Moreover, the lines showed inverse
      relationships between ROMs or OXY and body mass corrected for age. The results
      indicate that variation in oxidative status is heritable and linked to
      personality. This suggests that different animal personalities may be accompanied
      by differences in oxidative status, which may predict differences in longevity.

PMID- 18042512
TI  - Islands in the sea: extreme female natal site fidelity in the Australian sea
      lion, Neophoca cinerea.
AB  - Pinnipeds (seals, fur seals, sea lions and walrus) form large breeding
      aggregations with females often remaining faithful to a natal site or area. In
      these cases, females are philopatric to regional areas on broad geographical
      scales of hundreds to thousands of kilometers. An investigation of variation in a
      control region sequence of mtDNA in the Australian sea lion (Neophoca cinerea)
      has shown a case of extreme female natal site fidelity that has resulted in
      almost fixed population differentiation across its range (PhiST=0.93). This high
      level of population subdivision over short geographical distances (approx. 60 km)
      is unparalleled in any social marine mammal and reflects the unique life-history
      traits of this rare species. The high level of population subdivision and
      exclusive female natal site fidelity has important ramifications for conservation
      management, and poses many interesting questions of both academic and applied
      interest.

PMID- 18042513
TI  - Is Chernobyl radiation really causing negative individual and population-level
      effects on barn swallows?

PMID- 18042515
TI  - X-ray colour imaging.
AB  - A prototype X-ray colour imaging system has been assembled using the principle of
      tomographic energy-dispersive diffraction imaging (TEDDI). The new system has
      been tested using samples of nylon-6, aluminium powder and deer antler bone. Non
      destructive three-dimensional images of the test objects have been reconstructed
      on a 300 microm scale with an associated diffraction pattern at each voxel. In
      addition, the lattice parameters of the polycrystalline material present in the
      sampled voxels have been determined using full pattern refinement methods. The
      use of multiple diffracted parallel colour X-ray beams has allowed simultaneous
      spatially resolved data collection across a plane of the sample. This has
      simplified the sample scan motion and has improved data collection times by a
      factor scaling with the number of detector pixels. The TEDDI method is currently
      limited to thin samples (approx. 1-2mm) with light atoms owing to the very low
      detection efficiency of the silicon detector at X-ray energies above 25 keV. We
      describe how these difficulties can be removed by using semiconductor detectors
      made from heavier atomic material.

PMID- 18042516
TI  - A review of the evidence: nuts and body weight.
AB  - There is currently no single dietary or lifestyle intervention that is effective
      in long-term weight loss. Traditional weight loss diets tend to be low in total
      fat and therefore often restrict nut consumption. However, nuts are an important
      source of many vitamins, minerals, monounsaturated and polyunsaturated fatty
      acids. This paper reviewed all the available evidence from the literature in
      relation to nut consumption and body weight. The findings show that the role of
      nut consumption in body weight management is varied. Nuts, when included as part
      of an energy-controlled diet, were found in some instances to assist with weight
      loss. However, when nuts were added to an existing diet without controlling for
      energy intake, body weight increased, although to a lesser extent than
      theoretically predicted. There is limited evidence on the effect nut consumption
      has on type 2 diabetes, although available evidence indicates that nuts as part
      of a healthy diet do not cause weight gain and can have a positive influence on
      the fatty acid profile of a person with diabetes. This review shows there is a
      lack of evidence to support the restriction of nut consumption in weight
      management, indicating that further research is needed to assess the role of nuts
      in weight management.

PMID- 18042517
TI  - The lactase gene -13910T allele can not predict the lactase-persistence phenotype
      in north China.
AB  - The frequency of lactase persistence varies widely in human populations. Study
      showed that the T allele of a C/T transition 13910bp upstream from exon 1 of
      lactase gene (LCT) was completely associated with lactase persistence in a
      Finnish population. To evaluate if the frequency of -13910T allele was in
      concordance with the lactase persistence in northern Chinese populations, in this
      study, we used Polymerase Chain Reaction-Restriction Fragment Length Polymorphism
      (PCR-RFLP) to detect the lactase -13910T allelic frequency in 5 northern Chinese
      populations for the first time. Results showed that the T allele frequency was
      low in these populations and that it did not match the lactase persistence
      phenotype in these populations. Therefore the -13910T allelic frequency can not
      serve as a predictor of the lactase persistence in these populations and this
      suggests the existence of other possible mechanisms of lactose tolerance in
      Chinese populations.

PMID- 18042518
TI  - Alterations of atherogenic low-density lipoproteins and serum fatty acids after
      12 week moderate exercise training in sedentary Thai women.
AB  - The potential benefit of aerobic exercise upon cardiovascular disease (CVD)
      through an increasing high-density lipoproteins (HDLs) is acknowledged. However,
      its effects on low-density lipoproteins (LDLs) and their subpopulations, are
      unknown in Thailand. Twenty sedentary Thai women undertook a 12-week exercise
      training program (60% heart rate reserve) comprising 25-minute cycling followed
      by 10-minute warm-up/cool-down 3 times a week with a group of 20 matched
      sedentary subjects as control. Triacylglycerols (TGs) and cholesterol (C) of
      plasma lipoproteins including triacylglycerol-rich lipoproteins (TRLs), large,
      buoyant LDL (lb-LDL), small, dense LDL (sd-LDL) and HDLs were analyzed while
      serum fatty acid profiles were also assessed. It was found that plasma TGs, TRL
      TGs, sd-LDL-C and sd-LDL-C/lb-LDL-C (S/L) ratio decreased significantly after 12
      weeks of exercise to -9%, -8%, -17% and -19% respectively from baseline (p <
      0.05). Serum fatty acid profiles remained unchanged. No alteration of any
      parameters was found in the control group without exercise. These findings
      suggest that moderate exercise training, even without a change of HDLs, impedes
      the shift of lb-LDL to more atherogenic sd-LDL, thus possibly preventing
      cardiovascular disease in healthy, sedentary Thai women.

PMID- 18042519
TI  - Effect of purple sweet potato leaves consumption on the modulation of the immune
      response in basketball players during the training period.
AB  - The aim of this study was to evaluate the effect of the consumption of purple
      sweet potato leaves (PSPLs) on the immune response and the modulation of that
      response in 15 basketball players during a training period. They completed the 7
      week study consisted of a run-in period (week 1), a PSPLs diet (200 g PSPLs/d;
      weeks 2, 3), a washout period (weeks 4, 5), and a control diet (low polyphenols
      content and carotenoid content adjusted to the same level as that of PSPLs diet;
      weeks 6 and 7). Blood, urine, and saliva samples were collected for biochemical
      analysis. The results showed that the plasma polyphenols concentration increased
      significantly in the PSPLs period. Compared with the control period, the PSPLs
      consumption produced a significant increase in the proliferation responsiveness
      of peripheral blood mononuclear cells (PBMC), cytotoxic activity of nature killer
      (NK) cells, and secretion of interferon (IFN)-gamma. However, no significant
      increase in the secretion of salivary immunoglobulin A (sIgA), interleukin (IL)
      2, or interleukin-4 was observed after PSPLs consumption. In conclusion,
      consumption of a PSPLs diet for 2 weeks can modulate the immune response of
      basketball players during a training period.

PMID- 18042520
TI  - Fruits and stir-fried vegetables increase plasma carotenoids in young adults.
AB  - We examined the plasma levels of carotenoids in young adults after a dietary
      intervention composed of increased intakes of fruits and stir-fried vegetables
      from a Taiwanese mixed diet. Thirty-four apparently healthy, non-smoking subjects
      who normally ingested less than two and a half servings of fruits and vegetables
      daily were selected for the study. Meals changed were lunch and dinner on
      weekdays for a period of 4 weeks. The test meal consisted of three servings of
      stir-fried vegetables and two servings of fresh fruits. Plasma carotenoid levels
      in subjects significantly increased from 19%-32% for beta-carotene, 15%-47% for
      lycopene and 59%-88% for beta-crytoxanthin (p < 0.05) from week 1 to 4. However,
      these concentrations of beta-carotene and lycopene significantly decreased after
      stopping the consumption of the test meals. This study reveals the importance of
      a continuous consumption of carotenoid rich foods in order to maintain high
      levels of plasma carotenoids for the potential prevention of chronic diseases in
      individuals.

PMID- 18042521
TI  - Dietary plant sterols supplementation does not alter lipoprotein kinetics in men
      with the metabolic syndrome.
AB  - Dietary plant sterols supplementation has been demonstrated in some studies to
      lower plasma total and LDL cholesterol in hypercholesterolemic subjects. The
      cholesterol lowering action of plant sterols remains to be investigated in
      subjects with the metabolic syndrome. In a randomized, crossover study of 2 x 4
      week therapeutic periods with oral supplementation of plant sterols (2 g/day) or
      placebo, and two weeks placebo wash-out between therapeutic periods, we
      investigated the effects of dietary plant sterols on lipoprotein metabolism in
      nine men with the metabolic syndrome. Lipoprotein kinetics were measured using
      [D3]-leucine, gas chromatography-mass spectrometry and compartmental modeling. In
      men with the metabolic syndrome, dietary plant sterols did not have a significant
      effect on plasma concentrations of total cholesterol, triglycerides, LDL
      cholesterol, HDL cholesterol, apolipoprotein (apo) B, apoA-I or apoA-II. There
      were no significant changes to VLDL-, IDL-, LDL-apoB or apoA-I fractional
      catabolic rates and production rates between therapeutic phases. Relative to
      placebo, plasma campesterol, a marker of cholesterol absorption was significantly
      increased (2.53 +/- 0.35 vs. 4.64 +/- 0.59 mug/ml, p < 0.05), but there was no
      change in plasma lathosterol, a marker of endogenous cholesterol synthesis. In
      conclusion, supplementation with plant sterols did not appreciably influence
      plasma lipid or lipoprotein metabolism in men with the metabolic syndrome. Future
      studies with larger sample size, stratification to low and high cholesterol
      absorbers and cholesterol balance studies are warranted.

PMID- 18042522
TI  - Desirable intakes of polyunsaturated fatty acids in Indonesian adults.
AB  - A Indonesian Advisory Group on Fatty Acid Nutrition and Health was established in
      2004 to consider the increasing incidence of nutritionally-related cardiovascular
      disease in Indonesia. Emerging international recommendations, often focused on
      dietary fat and may not have been relevant to the national situation. Traditional
      dietary patterns were apparently protective against ischaemic heart disease often
      with fat derived dominantly from a particular source like coconut, soy, peanut or
      fish. These fats were used in ways which promoted the use of potentially
      cardioprotective foods like legumes, vegetables, fruits and aquatic food. Optimal
      intakes of polyunsaturated fatty acids in Indonesia are likely to reflect both
      absolute intakes and the relationships between n-3 and n-6 fatty acids of longer
      chain lengths. This leaves some issues for active and continuing review, like the
      intakes of trans fatty acids, and the regulatory and food labelling implications.
      Some studies underway and others which need implementation will enable the
      Advisory Group to prepare a second report with more basis in Indonesian evidence.
      In the meantime, the Advisory Group has recommended that the AHA (American Heart
      Association) and ISSFAL (International Society for the Study of Fatty Acids and
      Lipids) recommendations obtain until the end of 2007.

PMID- 18042523
TI  - Comparison of body compositional indices assessed by underwater weighing,
      bioelectrical impedance and anthropometry in Indonesian adolescent girls.
AB  - OBJECTIVE: To investigate the accuracy of bioelectric impedance analysis and
      anthropometry to assess percentage body fat (BF %) against underwater weighing
      (UW). DESIGN AND METHODS: A cross sectional study, 102 girls, aged 11-15, were
      recruited from two Junior High Schools in Jakarta. MEASUREMENTS: Measurements of
      percent-age body fat (BF%) using underwater weighing (UW), bioelectrical
      impedance analysis (BIA), Tanita BIA, body mass index (BMI) and skinfold
      equations. RESULTS: Correlation between different methods was significant (p <
      0.001). The mean difference of BF % from BIA, Tanita, BMI and skinfold compared
      to UW were 1.87 +/- 3.14, -3.46 +/- 3.28, 1.57 +/- 2.90 and -0.360 +/- 3.09,
      respectively. Assessments between UW and other methods were significantly
      different (p < 0.0001) except for skinfolds (p = 0.3031). CONCLUSION: The results
      between UW and other methods was significantly different, except for skinfolds.
      There was overestimation and underestimation of BF%. The agreement between
      skinfold measurement and underwater weighing was also influenced by menarche
      status.

PMID- 18042524
TI  - Percent body fat cutoff values for classifying overweight and obesity recommended
      by the International Obesity Task Force (IOTF) in Korean children.
AB  - OBJECTIVE: To predict the percent body fat (%BF) cutoff values corresponding to
      overweight and obesity recommended by the International Obesity Task Force (IOTF)
      in Korean children and to compare those values with the published cutoff values
      in Caucasian children. RESEARCH METHODS AND PROCEDURES: The sample consisted of
      1083 Korean children and adolescents (555 boys and 528 girls) aged 7-18 years
      from 3 schools. Body mass index (BMI) and %BF using a bioelectrical impedance
      analyzer were measured. The classification of overweight and obesity was based on
      the age- and sex-specific BMI cutoff values of the IOTF guidelines. RESULTS: The
      predicted %BF cutoff values for overweight and obesity varied by age and sex:
      overweight, 17-22% in boys and 24-37% in girls; obesity, 24-30% in boys and 30
      53% in girls. Those %BF cutoff values in older Korean boys tended to be lower
      than the published %BF cutoff values in Caucasian boys. While %BF cutoff values
      for overweight in Korean girls were similar to the values in Caucasian girls, %BF
      cutoff values for obesity in Korean girls aged 13-18 years were higher compared
      to cutoff values in Caucasian girls. CONCLUSION: The %BF values associated with
      the IOTF-recommended BMI cutoff values for overweight and obesity may require age
      and sex-specific cutoff values in Korean children aged 7-18 years.

PMID- 18042525
TI  - Population-specific anthropometric cut-points improve the functionality of the
      Mini Nutritional Assessment (MNA) in elderly Taiwanese.
AB  - The objective of this study was to determine the population-specific cut-points
      of body mass index (BMI), mid-arm circumference (MAC) and calf circumference (CC)
      for identifying subnormal nutritional status in elderly Taiwanese, and to
      evaluate the possibility of improving the functionality of the Mini Nutritional
      Assessment (MNA) by adopting these cut-points. This study analyzed data from 1583
      men and 1307 women, 65 years or older, of a national survey. The survey involved
      in-home, face-to-face, interviews and anthropometric measurements. Results showed
      that based on the cumulative percentile curves, the fifth percentile values were:
      BMI, 17 kg/m2 for both men and women; MAC, 22.5 cm for men and 21 cm for women;
      and CC, 28 cm for men and 25 cm for women. Substitution of these population
      specific cut-points for respective values in the MNA screen resulted in lowered
      proportions of elderly classified malnourished or at risk of malnutrition. The
      prevalence of malnutrition was reduced from 1.7% to 1.4% in men and from 2.4% to
      1.5% in women. The proportions classified at risk of malnutrition were reduced
      from 10.1% to 8.9% for men and 16.8% to 12.8% for women. In conclusion, results
      suggest that the MNA is a valuable tool for geriatric nutritional risk
      assessment. However, in populations where significant differences exist in
      anthropometric measurements from the Caucasian populations, population-specific
      cut-points should be used.

PMID- 18042526
TI  - Body fatness, physical activity, and nutritional behaviours in Asian Indian
      immigrants to New Zealand.
AB  - Body fatness, physical activity, and nutritional behaviours were assessed in 112
      (50 male, 62 female) Asian Indians living in New Zealand. Participants were aged
      44-91 years (mean 67.5 +/- 7.6) and had lived in New Zealand on average 51
      months. Height, weight, and waist circumference were measured to determine body
      mass index (BMI) and central adiposity. Bioelectrical impedance was used to
      derive fat free mass, fat mass, and percentage body fat. Pedometers were worn to
      record daily steps taken over each of seven consecutive days. A lifestyle and
      health questionnaire was administered to collect information on nutrition
      behaviours. Average BMI for the sample was 27.2 +/- 4.7 kg/m2 with females (28.0
      +/- 5.4 kg/m2) significantly higher than males (25.6 +/- 5.4 kg/m2). Using Asian
      Indian specific cut-offs 69% of the sample was obese (BMI>=25 kg/m2) and a
      further 13.7% overweight (23>=BMI<25 kg/m2). Average percentage body fat for the
      sample was 41.1 +/- 9.1 with females significantly higher than males. The
      majority (74%) reported some form of chronic condition, with 35% diagnosed with
      diabetes. Physical activity levels for the sample were low (5,977 +/- 3,560
      steps/day) and significantly different between males (6,982 +/- 4,426) and
      females (5,159 +/- 2,401). Higher pedometer steps were associated with lower
      waist circumference. After adjustment for age, physical activity was lower, but
      nutritional habits better for those who had spent a longer time in New Zealand.
      In summary, Asian Indian immigrants to New Zealand have low physical activity
      levels and high levels of overweight/obesity and lifestyle disease.

PMID- 18042527
TI  - Reduction of abdominal fat and chronic disease factors by lifestyle change in
      migrant Asian Indians older than 50 years.
AB  - The objective of this study was to assess the impact of a group diet and physical
      activity intervention on body composition, blood lipid profile and insulin
      resistance in migrant Asian Indian volunteers. Total body and abdominal fat,
      waist girth, serum glucose, insulin and lipids were measured one month before and
      immediately prior to an intervention designed to encourage increased physical
      activity and improved diet. Measurements were repeated after a 5-month period of
      altered exercise and dietary habits. Over this period monthly group education
      sessions were held on diet and physical activity and the importance of lifestyle
      changes to reduce risk factors for chronic disease. Forty one (21M, 20F)
      volunteers (aged > 50 y) were recruited from Asian Indian community groups in
      urban Auckland, New Zealand. Body weight, total and percentage body fat, waist
      girth and abdominal fat decreased in men following the intervention (p < 0.006)
      while these changes were not statistically significant in women. In both men and
      women high density lipoprotein (HDL) levels increased and LDL and total
      cholesterol/HDL ratio decreased (p < 0.002) without changes in serum glucose,
      insulin and triglycerides. Reduction in systolic and diastolic blood pressure was
      associated with an increase in HDL cholesterol in women (r = 0.63, p = 0.003, r =
      0.48, p = 0.03) but not in men (r = 0.09, p = 0.69, r = 0.04, p = 0.86). Over a
      five month period, an Asian Indian community group diet and physical activity
      intervention resulted in significant reductions in total and abdominal body fat
      and blood lipid risk factors but not in insulin sensitivity or resistance.

PMID- 18042528
TI  - Obesity and changes in body weight related to 10-year diabetes incidence in women
      in Taiwan.
AB  - This study aimed to investigate the relation of obesity and changes in body
      weight through adulthood with risks of type 2 diabetes. This study of 954 middle
      aged women free of diabetes (mean age, 37.1 +/- 9.6 years) was conducted in a
      hospital. The baseline and biannual health check-ups were performed from 1993 to
      2003. The cumulative incidence rate of type 2 diabetes was 3.64 per 1000 person
      years during the mean follow-up period of 10 years. 73.3% of subjects who
      developed type 2 diabetes were overweight (16.6%) or obese (56.7%). Obese
      subjects (body mass index more than 25 kg/m2) had a relative risk of type 2
      diabetes of 10.4 (95% confidence interval 2.95-36.9) compared with subjects with
      an optimal body mass index (18-22.9 kg/m2). Long-term weight gain was strongly
      related to the risk of type 2 diabetes. Each 1 kg of weight gain was associated
      with a 16% increase in risk of developing diabetes. This study indicated that
      obesity at young adult and weight gain appreciably increase risk for type 2
      diabetes. Maintaining a lean weight throughout adulthood seems to be beneficial
      in the primary prevention of type 2 diabetes.

PMID- 18042529
TI  - Body weight and weight loss: are health messages reaching their target?
AB  - OBJECTIVE: To investigate lay peoples' knowledge of health risks of overweight,
      accuracy of self-perception of body weight and perceived benefits of weight loss.
      METHOD: A nine item questionnaire was administered to a cross sectional survey of
      adults in metropolitan shopping centres, height and weight were measured.
      RESULTS: Two hundred and nine (57% female) adults completed the survey. Thirty
      eight percent had a healthy BMI (18.5-24.9), 38% were overweight (BMI 25-29.9)
      and a further 22% were obese (BMI > 30). However only 46% perceived themselves
      'overweight', 50% considered themselves 'just about right' and 4% considered
      themselves 'underweight'. Of those with a BMI of 25 or greater 28% considered
      their weight 'just about right'. Over 80% thought 'being overweight' was 'likely'
      or 'very likely' to be a risk factor for cardiovascular disease, hypertension,
      diabetes and stroke; however 20% of overweight or obese individuals did not think
      their health would improve if they lost weight. CONCLUSION: A significant
      proportion of overweight or obese individuals do not accurately perceive their
      body weight and do not recognise the health advantages of weight loss despite
      recognising excess body weight as a risk factor for chronic diseases.
      IMPLICATIONS: Increasing the awareness of an individual's BMI and promoting the
      benefits of modest weight loss maybe two underutilized strategies for population
      level weight control.

PMID- 18042530
TI  - Assessment of risks of "lifestyle" diseases including cardiovascular disease and
      type 2 diabetes by anthropometry in remote Australian Aborigines.
AB  - OBJECTIVE: To evaluate waist-to-height ratio (WTHR), waist girth and body mass
      index (BMI) as predictors of cardiovascular risk factors in Australian
      Aborigines. DESIGN: Indices were examined as predictors of mean blood pressures
      (BP), blood lipids, glucose, insulin and as predictors of hypertension, decreased
      HDL-cholesterol, elevated glucose and type 2 diabetes. SETTING: Aboriginal
      communities in remote north-west Australia. PARTICIPANTS: Four hundred and one
      adults. RESULTS: More than 80% of participants had WTHR > or = 0.5 or BMI > 22
      kg/m2 and 78% had increased waist girth (> 90 cm men; > 80 cm women). Adverse BP,
      blood lipids, glucose and insulin were associated with classification above the
      cutpoint for each index. For fasting glucose > or = 5.6 mmol/L, sensitivity was
      91% with WTHR, 87% with waist girth and 88% with BMI; respective specificities
      were 29%, 29% and 44%. Area under receiver operating characteristic (AUROC)
      curves gave only "fair" accuracy for any discriminatory variable. With diabetes
      AUROC for BMI (0.59, 95% CI 0.53, 0.65) was significantly lower than with other
      indices (WTHR 0.74, 95% CI 0.69, 0.79; girth 0.72, 95% CI 0.67, 0.78) but did not
      differ significantly for fasting glucose, HDL-cholesterol or hypertension. AUROC
      did not differ significantly between men and women for any outcomes. CONCLUSIONS:
      The indices did not discriminate well for diabetes or cardiovascular risk factors
      in these Aborigines, but waist girth or WTHR appeared more useful than BMI.
      Appropriate cutpoints are needed. WTHR is simple, does not need sex-specific
      cutpoints and could be useful in developing public health strategies.

PMID- 18042531
TI  - Determinants of plasma homocysteine levels and carotid intima-media thickness in
      Japanese.
AB  - Although hyperhomocysteinemia is considered to be a key risk factor for
      atherosclerosis, especially in Western countries, its role in the Asian
      population is still controversial. In this study, we evaluated the determinants
      of homocysteine and carotid intima-media thickness, a clinical marker for the
      detection of atherosclerosis, in Japanese. In 289 Japanese adults (age 37-86
      yrs), we screened plasma total homocysteine by high performance liquid
      chromatography and evaluated maximum carotid intima-media thickness by
      ultrasound. Other blood chemistry values were also measured. Total homocysteine
      levels were higher in men than in women and increased with age. In multiple
      regression analysis, adjusted for age and sex, serum creatinine was a powerful
      determinant of homocysteine (beta = 3.3, p < 0.01). Maximum carotid intima-media
      thickness was higher in men than in women and increased with age. When adjusted
      for age and sex, systolic blood pressure was independently correlated with
      maximum carotid intima-media thickness (beta = 0.001, p < 0.01). Our current
      results support previous findings that in addition to age and sex, serum
      creatinine and systolic blood pressure are independent determinants of
      homocysteine and carotid intima-media thickness, respectively.

PMID- 18042532
TI  - The relationship between maternal physical activity during pregnancy and birth
      weight.
AB  - INTRODUCTION: Earlier studies in India have demonstrated an inverse relationship
      between physical activity and birth weight in rural women who had high levels of
      physical activity related to agricultural and domestic activities. There are no
      data on urban Indian women from a wide range of socio-economic backgrounds with
      varying levels of physical activity. This study assessed the role of different
      domains of physical activity during pregnancy and its relation to birth weight.
      METHODS: Data on maternal anthropometry and maternal physical activity level were
      collected at the 1st trimester (baseline), the 2nd trimester and the 3rd
      trimester of pregnancy. Birth weight for 546 live born babies was measured
      immediately after delivery. RESULTS: The time spent in sedentary activities
      (median "cut-off" of 165 min/d) was significantly associated with maternal body
      weight in the first trimester of pregnancy (51.2 kg vs. 54.1 kg, p < 0.001).
      Women in the highest tertile of physical activity level in the 1st trimester were
      1.58 times (95% CI: 1.02-2.44) more likely of having a baby in the lowest tertile
      of birth weight with reference to the first tertile. This significant association
      continued after adjustment for maternal weight and energy intake. CONCLUSION: The
      present study shows that physical activity in the first trimester is associated
      with low birth weight in Indian babies.

PMID- 18042533
TI  - Comparisons of a chicken-based formula with soy-based formula in infants with cow
      milk allergy.
AB  - OBJECTIVE: To determine whether chicken-based formula can replace soy-based
      formula in infants with cow milk allergy. SUBJECTS AND METHODS: Thirty-eight
      infants with cow's milk allergy, aged between 2-24 months of age were randomized
      to receive either chicken-based formula or soy-based formula for 14 days.
      RESULTS: In the group of soy-based formula, 12 out of 18 infants had evidence of
      intolerance and could not continue with the formula. However, only 4 out of 20
      infants in the chicken-based formula group had evidence of clinical intolerance.
      All other 16 infants were fed the chicken-based formula with success. The number
      of infants who were intolerant to chicken formula was significantly lower than
      the number of those fed soy-based formula (p = 0.009). CONCLUSION: Chicken-based
      formula can be used more effectively than soy-based formula in infants with cow
      milk allergy.

PMID- 18042534
TI  - Anemia and intestinal parasite infection in school children in rural Vietnam.
AB  - OBJECTIVES: This study hypothesized that besides iron deficiency, intestinal
      parasites infection is also a determinant of anemia in schoolchildren in rural
      Vietnam. METHODS: 400 primary schoolchildren from 20 primary schools in Tam Nong
      district, a poor rural area in Vietnam, were randomly selected from enrollment
      lists. Venous blood (5ml) was collected in a cross sectional study and analyzed
      for hemoglobin (Hb), serum ferritin (SF), serum transferrin receptor (TfR), serum
      C-reactive protein (CRP) and total immunoglobulin E (IgE). Stools samples were
      examined for hookworm, Trichuris, and Ascaris infection. Logistic regression was
      used to assess the effect of intestinal parasites on anemia. RESULTS: The
      prevalence of anemia (Hb < 115g/l) was 25%. Iron deficiency (TfR > 8.5mg/L)
      occurred in 2% of the children. The prevalence of intestinal parasites was 92%
      with the highest prevalence for Trichuris (76%) and Ascaris (71%). More than 30%
      and 80% of the children showed an elevated CRP (> or = 8 mg/L) and IgE (> 90
      IU/ml) concentration. Anemia status was borderline significantly associated with
      SF and not associated with TfR and CRP. The prevalence odds ratio for Trichuris
      infection was 1.96 (95% CI 1.07-3.59) and 2.00 (95% CI 1.08-3.65) with iron
      deficiency reflected by TfR and SF, respectively. CONCLUSION: Anemia is highly
      prevalent among schoolchildren in Vietnam but may not be associated with iron
      deficiency. Trichuris infection is associated with a doubled risk of anemia, not
      mediated through iron deficiency. Chronic infection may play a role in anemia,
      but needs further investigation.

PMID- 18042535
TI  - Serum iron status in Orang Asli children living in endemic areas of soil
      transmitted helminths.
AB  - We conducted a cross sectional study to examine the association of intestinal
      parasitic infections and protein energy malnutrition (PEM) with iron-status
      indicators and anaemia among Orang Asli children in Selangor, Malaysia. A total
      of 281 children aged 2 - 15 years were studied. The data were collected using
      structured questionnaires, anthropometric measurements and laboratory analysis
      for blood and faecal samples. All children were infected either by A.
      lumbricoides, T. trichiura or hookworm and almost 19%, 26% and 3% of the children
      had severe infection of ascariasis, trichuriasis and hookworm infection
      respectively. The prevalence of giardiasis among them was 24.9%. Overall, 41.5%
      of the children were anaemic (haemoglobin < 11.0 g/dL). Of these 61.0% of the
      children had iron deficiency and 36.5% had iron deficiency anaemia (IDA), which
      accounted for 88.0% of anaemia in this population. Severe trichuriasis had the
      most significant correlation with anaemia and iron deficiency in this population.
      It contributed to low concentrations of haemoglobin, serum iron and serum
      ferritin and high total iron binding capacity (TIBC). Significant underweight and
      stunting were associated with low concentrations of haemoglobin and serum iron
      while significant wasting was significantly associated with low concentration of
      serum ferritin. Logistic regression analysis confirmed that severe trichuriasis
      was a strong predictor of IDA. It also confirmed that children who were
      significantly underweight and whose mother was working were independent
      predictors of IDA in this population.

PMID- 18042536
TI  - Investigation of intelligence quotient and psychomotor development in
      schoolchildren in areas with different degrees of iodine deficiency.
AB  - This investigation aims to observe the intelligence and psychomotor development
      of the schoolchildren in iodine deficiency (ID) areas after the adoption of
      Universal Salt Iodization (USI), and evaluate the effect of the adoption of USI
      on their intelligence and psychomotor development. 564 schoolchildren (306 males
      and 258 females, age range from 8 to 13 yrs) from areas with severe, moderate,
      and mild ID were investigated. Intelligence quotient (IQ) was measured by
      Combined Raven's test, second edition. Psychomotor development was examined by
      Jinyi Psychomotor Test Battery (JPB). We found that the IQ scores of all subjects
      in the severe and moderate ID areas were 102 +/- 15.6 and 99.5 +/-16.6
      respectively, lower than those in the mild ID areas (108 +/- 12.4, p < 0.01). The
      IQ scores correlated negatively with age (partial r = -0.17; beta = -1.95; p <
      0.0001). The total T scores of JPB of all subjects in the severe and moderate ID
      areas were 316 +/- 42.3 and 330 +/- 47.7 respectively, lower than those in the
      mild ID areas (342 +/- 48.1, p < 0.05). The total T scores of JPB correlated
      negatively with age (partial r = -0.15; beta = -4.94; p = 0.0006). We may
      conclude that after the adoption of USI in the ID areas investigated, USI has
      probably made a contribution to the partial recovery of intelligence and
      psychomotor development injured by ID in schoolchildren, and should be
      strengthened.

PMID- 18042537
TI  - Food intake patterns among Australian adolescents.
AB  - OBJECTIVES: This study aimed to evaluate the food intake patterns of adolescents
      with respect to the Australian Guide to Healthy Eating, and to examine variations
      in food intake patterns by age, gender and region of residence. DESIGN: Cross
      sectional online food survey administered through schools. PARTICIPANTS AND
      SETTING: In 2004-2005, 3841 secondary students in years seven (12-13 years) and
      nine (14-15 years) drawn from 37 secondary schools in Victoria, Australia
      completed an online food intake patterns survey. OUTCOME MEASURES: Food intake
      was measured by a Food Frequency Questionnaire (FFQ), and categorized according
      to the five basic food groups (fruit, vegetables, meat, dairy, cereal) and the
      'extra' food group as defined by the Australian Guide to Healthy Eating (AGHE).
      The foods groups were examined in the study population and compared across age,
      gender and region. RESULTS: Many adolescents in this sample reported food intakes
      that deviated substantially from recommendations of the AGHE. For example, two
      thirds of participants failed to consume foods from the five recommended food
      groups daily; over a third reported eating fruit 'rarely or never'; and 22%
      reported eating fast foods every day. Food intakes were generally more in line
      with dietary guidelines among girls than boys. Regional differences were less
      consistent, and there were few differences by age. CONCLUSION: A significant
      proportion of adolescents have food intakes that fall short of the
      recommendations outlined in the Australian Guide to Healthy Eating. This
      highlights the need for public health initiatives to promote healthier food
      intake patterns among adolescents.

PMID- 18042538
TI  - Adolescent home food environments and socioeconomic position.
AB  - Many adolescents have diets that are less than optimal, particularly adolescents
      of low socioeconomic position (SEP). The determinants of SEP differences in
      adolescent dietary intake are poorly understood. This study examined the home
      food environments of adolescents and specifically investigated whether low SEP
      adolescents have less supportive home meal environments, fewer eating rules and
      poorer home availability of fruit and vegetables than adolescents of high SEP. A
      cross-sectional, self-reported survey was administered to 3,264 adolescents in
      years 7 and 9, from 37 secondary schools in Victoria, Australia. Adolescent
      perceptions of the home meal environment, eating rules and home food availability
      were described and compared across SEP, which was measured using maternal
      education. Maternal education was linked to various aspects of the home meal
      environment, as well as home food availability, but not to eating rules. Low SEP
      adolescents were more likely to report that they were always allowed to watch
      television during meal times, and that unhealthy foods were always or usually
      available at home. In contrast, high SEP adolescents were more likely to report
      that vegetables were always served at dinner, that the evening meal was never an
      unpleasant time and always or usually a time for family connectedness, and that
      fruit was always or usually available at home. This study highlights aspects of
      the home food environment that might explain SEP variation in adolescent diets.
      Feasible ways of increasing home availability of healthy foods, and encouraging
      home meal environments to be supportive of healthy eating should be explored,
      particularly in households of low SEP adolescents.

PMID- 18042539
TI  - Associations between dietary habits and risk factors for cardiovascular diseases
      in a Hong Kong Chinese working population--the "Better Health for Better Hong
      Kong" (BHBHK) health promotion campaign.
AB  - Diet and nutritional status have been shown to play pivotal roles in the
      occurrence of many chronic diseases. In this study, we examined the patterns of
      dietary habits and their relationships with risk factors for cardiovascular and
      chronic diseases in Hong Kong working populations. In April 2000, a 5-year
      territory-wide health promotion campaign supported by the Li Ka Shing Foundation
      was launched in Hong Kong by the Health InfoWorld of Hospital Authority. Between
      July 2000 and March 2002, 4841 Chinese subjects [2375 (49.1%) men and 2466
      (50.9%) women, mean age: 42.4 +/- 8.9 years (median: 43.0 years, range: 17-83
      years)] from the general working class were recruited. Subjects were randomly
      selected using computer generated codes according to the distribution of
      occupational groups. A dietary questionnaire was used to assess 6 core dietary
      habits: daily fruit intake, vegetable intake, fluid intake, sugary drinks,
      regularity of daily meals and number of dining out each day. Overall, men had a
      worse cardiovascular risk profile and less desirable dietary habits than women.
      Those who had more unhealthy dietary habits were more likely to be obese and
      current smokers. Using logistic regression analysis with the dietary habits as
      independent variables, we found that obesity, smoking and constipation were
      independently associated with various unhealthy dietary patterns. In conclusion,
      there were close associations between dietary habits and risk factors for
      cardiovascular diseases in Hong Kong. More effective community education about
      healthy lifestyle is required in Hong Kong.

PMID- 18042540
TI  - Meal distribution, relative validity and reproducibility of a meal-based food
      frequency questionnaire in Taiwan.
AB  - Food frequency questionnaire is an important assessment tool for public health
      nutrition research. We describe the development history and conducted the
      validity and reproducibility studies for a meal-based Chinese food frequency
      questionnaire (Chinese FFQ) by five meal sequences. A total of 51 subjects were
      recruited to collect dietary information twice (6 months apart) with one 24-hr
      recall, 7-day food records and the Chinese FFQ. Combining data from both time
      sets, Chinese FFQ showed strong correlations of macro and micronutrients with 7
      day records (n = 60, r = 0.29-0.50, p < 0.05), but not with 24-hr recalls (n =
      60, r = 0.01-0.23, p > 0.05). The reproducibility of this Chinese FFQ (n = 22)
      was consistently high for most nutrients, with Spearman correction coefficients
      between 0.42 for vitamin A to 0.79 for vitamin B12. From a larger sample of 231
      subjects who completed the Chinese FFQ and one 24-hr recall, we found the energy
      distributions of breakfast, lunch, dinner, afternoon and evening snacks combined
      from Chinese FFQ were 20%, 37%, 37% and 6%, and from 24-hour recalls were 19%,
      36%, 44% and 1%, respectively. These results showed acceptable reproducibility
      and relative validity of this meal-based Chinese FFQ.

PMID- 18042541
TI  - Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival
      by the B55alpha regulatory subunit targeting of the protein phosphatase 2A
      holoenzyme to Akt.
AB  - Akt is a protein serine/threonine kinase that is involved in the regulation of
      diverse cellular processes. Phosphorylation of Akt at regulatory residues Thr-308
      and Ser-473 leads to its full activation. The protein phosphatase 2A (PP2A) has
      long been known to negatively regulate Akt activity. The PP2A holoenzyme consists
      of the structural subunit (A), catalytic subunit (C), and a variable regulatory
      subunit (B). Here we report the identification of the specific B regulatory
      subunit that targets the PP2A holoenzyme to Akt. We found endogenous association
      of PP2A AB55C holoenzymes with Akt by co-immunoprecipitation analyses in pro
      lymphoid FL5.12 cells. Akt was shown to associate with ectopically expressed
      B55alpha subunit in NIH3T3 cells. The direct interaction between B55alpha subunit
      and Akt was confirmed using in vitro pulldown analyses. Intriguingly, we found
      that overexpression of B55alpha subunit significantly impaired phosphorylation at
      Thr-308, but to a lesser extent at Ser-473 of Akt in both FL5.12 and NIH3T3
      cells. Concomitantly, phosphorylation of a subset of Akt substrates, including
      FoxO3a, was substantially decreased by B55alpha overexpression in these cells.
      Silencing of B55alpha expression markedly increased phosphorylation at Thr-308
      but not at Ser-473 in both FL5.12 cells and NIH3T3 cells. Consistently, PP2A
      AB55alphaC holoenzymes preferentially dephosphorylated phospho-Thr-308 rather
      than phospho-Ser-473 in in vitro dephosphorylation assays. Furthermore, B55alpha
      overexpression retarded proliferation of NIH3T3 cells, and knockdown of B55alpha
      expression increased survival of FL5.12 cells upon interleukin-3 deprivation.
      Together, our data demonstrate that B55alpha-dependent targeting of the PP2A
      holoenzyme to Akt selectively regulates Akt phosphorylation at Thr-308 to
      regulate cell proliferation and survival.

PMID- 18042542
TI  - Induction of cell membrane protrusions by the N-terminal glutaredoxin domain of a
      rare splice variant of human thioredoxin reductase 1.
AB  - The human thioredoxin system has a wide range of functions in cells including
      regulation of cell proliferation and differentiation, immune system modulation,
      antioxidant defense, redox control of transcription factor activity, and
      promotion of cancer development. A key component of this enzymatic system is the
      selenoprotein thioredoxin reductase 1 (TrxR1), encoded by the TXNRD1 gene.
      Transcription of TXNRD1 involves alternative splicing, leading to a number of
      transcripts also encoding isoforms of TrxR1 that differ from each other at their
      N-terminal domains. Here we have studied the TXNRD1_v3 isoform containing an
      atypical N-terminal glutaredoxin (Grx) domain. Expression of the transcript of
      this isoform was found predominantly in testis but was also detected in ovary,
      spleen, heart, liver, kidney, and pancreas. By immunohistochemical analysis in
      human testis with antibodies specific for the Grx domain of TXNRD1_v3, the
      protein was found to be predominantly expressed in the Leydig cells. Expression
      of the TXNRD1_v3 transcript was also found in several cancer cell lines (HCC1937,
      H23, A549, U1810, or H157), and in HeLa cells, it was induced by estradiol or
      testosterone treatments. Surprisingly, green fluorescent protein fusions with the
      complete TXNRD1_v3 protein or with only its Grx domain localized to distinct
      cellular sites in proximity to actin, and furthermore, had a potent capacity to
      rapidly induce cell membrane protrusions. Analyses of these structures suggested
      that the Grx domain of TXNRD1_v3 localizes first in the emerging protrusion and
      is then followed into the protrusions by actin and subsequently by tubulin. The
      results presented thus reveal that TXNRD1_v3 has a unique and distinct expression
      pattern in human cells and suggest that the protein can guide actin
      polymerization in relation to cell membrane restructuring.

PMID- 18042543
TI  - The regulatory element in the 3'-untranslated region of human papillomavirus 16
      inhibits expression by binding CUG-binding protein 1.
AB  - The 3'-untranslated regions (UTRs) of human papillomavirus 16 (HPV16) and bovine
      papillomavirus 1 (BPV1) contain a negative regulatory element (NRE) that inhibits
      viral late gene expression. The BPV1 NRE consists of a single 9-nucleotide (nt)
      U1 small nuclear ribonucleoprotein (snRNP) base pairing site (herein called a U1
      binding site) that via U1 snRNP binding leads to inhibition of the late poly(A)
      site. The 79-nt HPV16 NRE is far more complicated, consisting of 4 overlapping
      very weak U1 binding sites followed by a poorly understood GU-rich element (GRE).
      We undertook a molecular dissection of the HPV16 GRE and identify via UV cross
      linking, RNA affinity chromatography, and mass spectrometry that is bound by the
      CUG-binding protein 1 (CUGBP1). Reporter assays coupled with knocking down CUGBP1
      levels by small interfering RNA and Dox-regulated shRNA, demonstrate CUGBP1 is
      inhibitory in vivo. CUGBP1 is the first GRE-binding protein to have RNA
      interfering knockdown evidence in support of its role in vivo. Several fine-scale
      GRE mutations that inactivate GRE activity in vivo and GRE binding to CUGBP1 in
      vitro are identified. The CUGBP1.GRE complex has no activity on its own but
      specifically synergizes with weak U1 binding sites to inhibit expression in vivo.
      No synergy is seen if the U1 binding sites are made weaker by a 1-nt down
      mutation or made stronger by a 1-nt up-mutation, underscoring that the GRE
      operates only on weak sites. Interestingly, inhibition occurs at multiple levels,
      in particular at the level of poly(A) site activity, nuclear-cytoplasmic export,
      and translation of the mRNA. Implications for understanding the HPV16 life cycle
      are discussed.

PMID- 18042544
TI  - The key residue for substrate transport (Glu14) in the EmrE dimer is asymmetric.
AB  - Transport proteins exhibiting broad substrate specificities are major
      determinants for the phenomenon of multidrug resistance. The Escherichia coli
      multidrug transporter EmrE, a 4-transmembrane, helical 12-kDa membrane protein,
      forms a functional dimer to transport a diverse array of aromatic, positively
      charged substrates in a proton/drug antiport fashion. Here, we report (13)C
      chemical shifts of the essential residue Glu(14) within the binding pocket. To
      ensure a native environment, EmrE was reconstituted into E. coli lipids.
      Experiments were carried out using one- and two-dimensional double quantum
      filtered (13)C solid state NMR. For an unambiguous assignment of Glu(14), an E25A
      mutation was introduced to create a single glutamate mutant. Glu(14) was (13)C
      labeled using cell-free expression. Purity, labeling, homogeneity, and
      functionality were probed by mass spectrometry, NMR spectroscopy, freeze fracture
      electron microscopy, and transport assays. For Glu(14), two distinct sets of
      chemical shifts were observed that indicates structural asymmetry in the binding
      pocket of homodimeric EmrE. Upon addition of ethidium bromide, chemical shift
      changes and altered line shapes were observed, demonstrating substrate
      coordination by both Glu(14) in the dimer.

PMID- 18042545
TI  - p38alpha stabilizes interleukin-6 mRNA via multiple AU-rich elements.
AB  - AU-rich elements (AREs) in the 3'-untranslated region (UTR) of unstable mRNA
      dictate their degradation or mediate translational repression. Cell signaling
      through p38alpha MAPK is necessary for post-transcriptional regulation of many
      pro-inflammatory cytokines. Here, the cis-acting elements of interleukin-6 (IL-6)
      3'-UTR mRNA that required p38alpha signaling for mRNA stability and translation
      were identified. Using mouse embryonic fibroblasts (MEFs) derived from
      p38alpha(+/+) and p38alpha(-/-) mice, we observed that p38alpha is obligatory for
      the IL-1-induced IL-6 biosynthesis. IL-6 mRNA stability is promoted by p38alpha
      via 3'-UTR. To understand the mechanism of cis-elements regulated by p38alpha at
      post-transcriptional level, truncation of 3'-UTR and the full-length 3'-UTR with
      individual AUUUA motif mutation placed in gene reporter system was employed.
      Mutation-based screen performed in p38alpha(+/+) and p38alpha(-/-) mouse
      embryonic fibroblast cells revealed that ARE1, ARE2, and ARE5 in IL-6 3'-UTR were
      targeted by p38alpha, and truncation-based screen showed that IL-6 3'-UTR-(56
      173) was targeted by p38alpha to stable mRNA. RNA secondary structure analysis
      indicated that modulated reporter gene expression was consistent with predicted
      secondary structure changes.

PMID- 18042546
TI  - Characterization of zfs1 as an mRNA-binding and -destabilizing protein in
      Schizosaccharomyces pombe.
AB  - Tristetraprolin is a vertebrate CCCH tandem zinc finger protein that can bind to
      and destabilize certain mRNAs containing AU-rich element binding sites. zfs1 is
      the single gene in the fission yeast, Schizosaccharomyces pombe, that encodes a
      protein containing the critical features of the tristetraprolin zinc finger
      domain. zfs1 has been linked to pheromone signal transduction control and to the
      coordination of mitosis, but no biological function has been ascribed to the zfs1
      protein. Through a functional genomics approach we compared transcript levels in
      wild-type and zfs1-deficient S. pombe strains; those elevated in the zfs1
      deficient strain were examined for the presence of potential tristetraprolin-like
      binding sites. One such potential target transcript was encoded by arz1, a gene
      encoding a protein of unknown function that contains armadillo repeats. arz1 mRNA
      decay was inhibited in the zfs1-deficient strain when it was expressed under the
      control of a thiamine-repressible promoter. Mutations within one AU-rich element
      present in the arz1 3'-untranslated region protected this transcript from zfs1
      promoted decay, whereas mutating another potential binding site had no effect.
      Binding assays confirmed a direct interaction between zfs1 and arz1 mRNA-based
      probes; this interaction was eliminated when key residues were mutated in either
      zfs1 zinc finger. zfs1 and its targets in S. pombe represent a useful model
      system for studies of zinc finger protein/AU-rich element interactions that
      result in mRNA decay.

PMID- 18042548
TI  - Deconvoluting the Cu2+ binding modes of full-length prion protein.
AB  - The prion protein (PrP) is a cell-surface Cu(2+)-binding glycoprotein that when
      misfolded is responsible for a number of transmissible spongiform
      encephalopathies. Full-length PrP-(23-231) and constructs in which the octarepeat
      region has been removed, or His(95) and His(110) is replaced by alanine residues,
      have been used to elucidate the order and mode of Cu(2+) coordination to PrP-(23
      231). We have built on our understanding of the appearance of visible CD spectra
      and EPR for various PrP fragments to characterize Cu(2+) coordination to full
      length PrP. At physiological pH, Cu(2+) initially binds to full-length PrP in the
      amyloidogenic region between the octarepeats and the structured domain at His(95)
      and His(110). Only subsequent Cu(2+) ions bind to single histidine residues
      within the octarepeat region. Ni(2+) ions are used to further probe metal binding
      and, like Cu(2+), Ni(2+) will bind individually to His(95) and His(110),
      involving preceding main chain amides. Competitive chelators are used to
      determine the affinity of the first mole equivalent of Cu(2+) bound to full
      length PrP; this approach places the affinity in the nanomolar range. The
      affinity and number of Cu(2+) binding sites support the suggestion that PrP could
      act as a sacrificial quencher of free radicals generated by copper redox cycling.

PMID- 18042547
TI  - Carbohydrate-response element-binding protein deletion alters substrate
      utilization producing an energy-deficient liver.
AB  - Livers from mice lacking the carbohydrate-responsive element-binding protein
      (ChREBP) were compared with wild type (WT) mice to determine the effect of this
      transcription factor on hepatic energy metabolism. The pyruvate dehydrogenase
      complex was considerably more active in ChREBP(-/-) mice because of diminished
      pyruvate dehydrogenase kinase activity. Greater pyruvate dehydrogenase complex
      activity caused a stimulation of lactate and pyruvate oxidation, and it
      significantly impaired fatty acid oxidation in perfused livers from ChREBP(-/-)
      mice. This shift in mitochondrial substrate utilization led to a 3-fold reduction
      of the free cytosolic [NAD(+)]/[NADH] ratio, a 1.7-fold increase in the free
      mitochondrial [NAD(+)]/[NADH] ratio, and a 2-fold decrease in the free cytosolic
      [ATP]/[ADP][P(i)] ratio in the ChREBP(-/-) liver compared with control. Hepatic
      pyruvate carboxylase flux was impaired with ChREBP deletion secondary to
      decreased fatty acid oxidation, increased pyruvate oxidation, and limited
      pyruvate availability because of reduced activity of liver pyruvate kinase and
      malic enzyme, which replenish pyruvate via glycolysis and pyruvate cycling.
      Overall, the shift from fat utilization to pyruvate and lactate utilization
      resulted in a decrease in the energy of ATP hydrolysis and a hypo-energetic state
      in the livers of ChREBP(-/-) mice.

PMID- 18042549
TI  - Prostaglandin E2 regulates angiogenesis via activation of fibroblast growth
      factor receptor-1.
AB  - Prostaglandin E(2) (PGE(2)) behaves as a mitogen in epithelial tumor cells as
      well as in many other cell types. We investigated the actions of PGE(2) on
      microvascular endothelial cells (capillary venular endothelial cells) with the
      purpose of delineating the signaling pathway leading to the acquisition of the
      angiogenic phenotype and to new vessel formation. PGE(2) (100 nM) produced
      activation of the fibroblast growth factor receptor 1 (FGFR-1), as measured by
      its phosphorylation, but not of vascular endothelial growth factor receptor 2.
      PGE(2) stimulated the EP3 subtype receptor, as deduced by abrogation of EP3
      Galpha(i) subunit activity through pertussis toxin. Consistent with this result,
      in human umbilical venular endothelial cells missing the EP3 receptor, PGE(2) did
      not phosphorylate FGFR-1. Upon binding to its receptor, PGE(2) initiated an
      autocrine/paracrine signaling cascade involving the intracellular activation of c
      Src, activation of matrix metalloproteinase (predominantly MMP2), which in turn
      caused the mobilization of membrane-anchored fibroblast growth factor-2 (FGF-2).
      In fact, in cells unable to release FGF-2 the transfection with both FGFR-1 and
      EP3 did not result in FGFR-1 phosphorylation in response to PGE(2). Relevance for
      the FGF2-FGFR-1 system was highlighted by confocal analysis, showing receptor
      internalization after cell exposure to the prostanoid. ERK1/2 appeared to be the
      distal signal involved, its phosphorylation being sensitive to either cSrc
      inhibitor or FGFR-1 blocker. Finally, PGE(2) stimulated cell migration and
      capillary formation in aortic rings, which were severely reduced by inhibitors of
      signaling molecules or by receptor antagonist. In conclusion, this study provides
      evidence for the involvement of FGFR-1 through FGF2 in eliciting PGE(2)
      angiogenic responses. This signaling pattern is similar to the autocrine
      paracrine mechanism which operates in endothelial cells to support neovascular
      growth.

PMID- 18042550
TI  - DJ-1 decreases Bax expression through repressing p53 transcriptional activity.
AB  - DJ-1, originally identified as an oncogene product, is a protein with various
      functions in cellular transformation, oxidative stress response, and
      transcriptional regulation. Although previous studies suggest that DJ-1 is
      cytoprotective, the mechanism by which DJ-1 exerts its survival functions remains
      largely unknown. Here we show that DJ-1 exerts its cytoprotection through
      inhibiting p53-Bax-caspase pathway. DJ-1 interacts with p53 in vitro and in vivo.
      Overexpression of DJ-1 decreases the expression of Bax and inhibits caspase
      activation, whereas knockdown of DJ-1 increases Bax protein levels and
      accelerates caspase-3 activation and cell death induced by UV exposure. Our data
      provide evidence that the protective effects of DJ-1 on apoptosis are associated
      with its ability of decreasing Bax level through inhibiting p53 transcriptional
      activity.

PMID- 18042551
TI  - Bone morphogenetic protein (BMP) type II receptor is required for BMP-mediated
      growth arrest and differentiation in pulmonary artery smooth muscle cells.
AB  - Bone morphogenetic protein (BMP) signals regulate the growth and differentiation
      of diverse lineages. The association of mutations in the BMP type II receptor
      (BMPRII) with idiopathic pulmonary arterial hypertension suggests an important
      role of this receptor in vascular remodeling. Pulmonary artery smooth muscle
      cells lacking BMPRII can transduce BMP signals using ActRIIa (Activin type II
      receptor). We investigated whether or not BMP signaling via the two receptors
      leads to differential effects on vascular smooth muscle cells. BMP4, but not
      BMP7, inhibited platelet-derived growth factor-activated proliferation in wild
      type pulmonary artery smooth muscle cells, whereas neither ligand inhibited the
      growth of BMPRII-deficient cells. Adenoviral gene transfer of BMPRII enabled
      BMP4, as well as BMP7, to inhibit proliferation in BMPRII-deficient cells. BMP
      mediated growth inhibition was also reconstituted by the BMPRII short isoform,
      lacking the C-terminal domain present in the long form. BMP4, but not BMP7,
      induced the expression of osteoblast markers in wild-type cells, whereas neither
      ligand induced these markers in BMPRII-deficient cells. Overexpression of short
      or long forms of BMPRII in BMPRII-deficient cells enabled BMP4 and BMP7 to induce
      osteogenic differentiation. Although signaling via BMPRII or ActRIIa transiently
      activated SMAD1/5/8, only BMPRII signaling led to persistent SMAD1/5/8 activation
      and sustained increases in Id1 mRNA and protein expression. Pharmacologic
      blockade of BMP type I receptor function within 24 h after BMP stimulation
      abrogated differentiation. These data suggest that sustained BMP pathway
      activation, such as that mediated by BMPRII, is necessary for growth and
      differentiation control in vascular smooth muscle.

PMID- 18042552
TI  - Hepatic CTP:phosphocholine cytidylyltransferase-alpha is a critical predictor of
      plasma high density lipoprotein and very low density lipoprotein.
AB  - CTP:phosphocholine cytidylyltransferase (CT) is the key regulatory enzyme in the
      CDP-choline pathway for the biosynthesis of phosphatidylcholine (PC). We
      previously generated a mouse in which the hepatic CTalpha gene was specifically
      inactivated by the cre/loxP procedure. In CTalpha knock-out mice, plasma high
      density lipoprotein (HDL) and very low density lipoprotein (VLDL) levels were
      markedly lower than in wild type mice (Jacobs, R. L., Devlin, C., Tabas, I., and
      Vance, D. E. (2004) J. Biol. Chem. 279, 47402-47410.) To investigate the
      mechanism(s) responsible for the decrease in plasma lipoprotein levels, we
      isolated primary hepatocytes from knock-out and wild type mice. ABCA1 expression
      was reduced in knock-out hepatocytes and apoAI-dependent cholesterol, and PC
      efflux was impaired. When knock-out hepatocytes were infected with an adenovirus
      expressing CTalpha, apoAI-dependent PC efflux returned partially, whereas
      cholesterol efflux and ABCA1 levels were not restored to normal levels.
      Adenoviral expression of CTalpha did not increase VLDL secretion in knock-out
      hepatocytes, even though cellular PC levels returned to normal. However, in vivo
      adenoviral delivery of CTalpha normalized plasma HDL and VLDL levels in knock-out
      mice. The observations demonstrate that hepatic PC biosynthesis is a key player
      in maintaining plasma VLDL and HDL, and further underscores the importance of the
      liver in HDL formation.

PMID- 18042553
TI  - Identification of differentially expressed gene categories in microarray studies
      using nonparametric multivariate analysis.
AB  - MOTIVATION: The field of microarray data analysis is shifting emphasis from
      methods for identifying differentially expressed genes to methods for identifying
      differentially expressed gene categories. The latter approaches utilize a priori
      information about genes to group genes into categories and enhance the
      interpretation of experiments aimed at identifying expression differences across
      treatments. While almost all of the existing approaches for identifying
      differentially expressed gene categories are practically useful, they suffer from
      a variety of drawbacks. Perhaps most notably, many popular tools are based
      exclusively on gene-specific statistics that cannot detect many types of
      multivariate expression change. RESULTS: We have developed a nonparametric
      multivariate method for identifying gene categories whose multivariate expression
      distribution differs across two or more conditions. We illustrate our approach
      and compare its performance to several existing procedures via the analysis of a
      real data set and a unique data-based simulation study designed to capture the
      challenges and complexities of practical data analysis. We show that our method
      has good power for differentiating between differentially expressed and non
      differentially expressed gene categories, and we utilize a resampling based
      strategy for controlling the false discovery rate when testing multiple
      categories. AVAILABILITY: R code (www.r-project.org) for implementing our
      approach is available from the first author by request.

PMID- 18042554
TI  - An assessment of the uses of homologous interactions.
AB  - MOTIVATION: Protein-protein interactions have proved to be a valuable starting
      point for understanding the inner workings of the cell. Computational
      methodologies have been built which both predict interactions and use interaction
      datasets in order to predict other protein features. Such methods require gold
      standard positive (GSP) and negative (GSN) interaction sets. Here we examine and
      demonstrate the usefulness of homologous interactions in predicting good quality
      positive and negative interaction datasets. RESULTS: We generate GSP interaction
      sets as subsets from experimental data using only interaction and sequence
      information. We can therefore produce sets for several species (many of which at
      present have no identified GSPs). Comprehensive error rate testing demonstrates
      the power of the method. We also show how the use of our datasets significantly
      improves the predictive power of algorithms for interaction prediction and
      function prediction. Furthermore, we generate GSN interaction sets for yeast and
      examine the use of homology along with other protein properties such as
      localization, expression and function. Using a novel method to assess the
      accuracy of a negative interaction set, we find that the best single selector for
      negative interactions is a lack of co-function. However, an integrated method
      using all the characteristics shows significant improvement over any current
      method for identifying GSN interactions. The nature of homologous interactions is
      also examined and we demonstrate that interologs are found more commonly within
      species than across species. CONCLUSION: GSP sets built using our homologous
      verification method are demonstrably better than standard sets in terms of
      predictive ability. We can build such GSP sets for several species. When
      generating GSNs we show a combination of protein features and lack of homologous
      interactions gives the highest quality interaction sets. AVAILABILITY: GSP and
      GSN datasets for all the studied species can be downloaded from
      http://www.stats.ox.ac.uk/~deane/HPIV.

PMID- 18042555
TI  - Choosing BLAST options for better detection of orthologs as reciprocal best hits.
AB  - MOTIVATION: The analyses of the increasing number of genome sequences requires
      shortcuts for the detection of orthologs, such as Reciprocal Best Hits (RBH),
      where orthologs are assumed if two genes each in a different genome find each
      other as the best hit in the other genome. Two BLAST options seem to affect
      alignment scores the most, and thus the choice of a best hit: the filtering of
      low information sequence segments and the algorithm used to produce the final
      alignment. Thus, we decided to test whether such options would help better detect
      orthologs. RESULTS: Using Escherichia coli K12 as an example, we compared the
      number and quality of orthologs detected as RBH. We tested four different
      conditions derived from two options: filtering of low-information segments, hard
      (default) versus soft; and alignment algorithm, default (based on matching words)
      versus Smith-Waterman. All options resulted in significant differences in the
      number of orthologs detected, with the highest numbers obtained with the
      combination of soft filtering with Smith-Waterman alignments. We compared these
      results with those of Reciprocal Shortest Distances (RSD), supposed to be
      superior to RBH because it uses an evolutionary measure of distance, rather than
      BLAST statistics, to rank homologs and thus detect orthologs. RSD barely
      increased the number of orthologs detected over those found with RBH. Error
      estimates, based on analyses of conservation of gene order, found small
      differences in the quality of orthologs detected using RBH. However, RSD showed
      the highest error rates. Thus, RSD have no advantages over RBH. AVAILABILITY:
      Orthologs detected as Reciprocal Best Hits using soft masking and Smith-Waterman
      alignments can be downloaded from http://popolvuh.wlu.ca/Orthologs.

PMID- 18042556
TI  - Reconstructing protein networks of epithelial differentiation from histological
      sections.
AB  - MOTIVATION: For systems biology of complex stratified epithelia like human
      epidermis, it will be of particular importance to reconstruct the spatiotemporal
      gene and protein networks regulating keratinocyte differentiation and
      homeostasis. RESULTS: Inside the epidermis, the differentiation state of
      individual keratinocytes is correlated with their respective distance from the
      connective tissue. We here present a novel method to profile this correlation for
      multiple epithelial protein biomarkers in the form of quantitative spatial
      profiles. Profiles were computed by applying image processing algorithms to
      histological sections stained with tri-color indirect immunofluorescence. From
      the quantitative spatial profiles, reflecting the spatiotemporal changes of
      protein expression during cellular differentiation, graphs of protein networks
      were reconstructed. CONCLUSION: Spatiotemporal networks can be used as a means
      for comparing and interpreting quantitative spatial protein expression profiles
      obtained from different tissue samples. In combination with automated
      microscopes, our new method supports the large-scale systems biological analysis
      of stratified epithelial tissues.

PMID- 18042557
TI  - Estimating parameters and hidden variables in non-linear state-space models based
      on ODEs for biological networks inference.
AB  - MOTIVATION: Statistical inference of biological networks such as gene regulatory
      networks, signaling pathways and metabolic networks can contribute to build a
      picture of complex interactions that take place in the cell. However, biological
      systems considered as dynamical, non-linear and generally partially observed
      processes may be difficult to estimate even if the structure of interactions is
      given. RESULTS: Using the same approach as Sitz et al. proposed in another
      context, we derive non-linear state-space models from ODEs describing biological
      networks. In this framework, we apply Unscented Kalman Filtering (UKF) to the
      estimation of both parameters and hidden variables of non-linear state-space
      models. We instantiate the method on a transcriptional regulatory model based on
      Hill kinetics and a signaling pathway model based on mass action kinetics. We
      successfully use synthetic data and experimental data to test our approach.
      CONCLUSION: This approach covers a large set of biological networks models and
      gives rise to simple and fast estimation algorithms. Moreover, the Bayesian tool
      used here directly provides uncertainty estimates on parameters and hidden
      states. Let us also emphasize that it can be coupled with structure inference
      methods used in Graphical Probabilistic Models. AVAILABILITY: Matlab code
      available on demand.

PMID- 18042558
TI  - Epidural anaesthetic effect of the 8% emulsified isoflurane: a study in rabbits.
AB  - BACKGROUND: Studies have shown that local use of volatile anaesthetics produce
      local anaesthetic effects such as local infiltration anaesthesia (in rats and
      humans) and spinal anaesthesia (in dogs). However, there is still no report on
      the epidural anaesthetic effect of volatile anaesthetics. The aim of the present
      study was to evaluate the epidural anaesthetic effect of the 8% emulsified
      isoflurane in rabbits. METHODS: Forty rabbits chronically instrumented with an
      epidural catheter were randomly divided into four groups of 10 rabbits each.
      According to group assignment, rabbits received epidural administration of 8%
      emulsified isoflurane (v/v) 1 ml in the E-isoflurane group, 1% lidocaine 1 ml in
      the Lidocaine group, 30% lipid emulsion 1 ml in the Itralipid group, or normal
      saline 1 ml in the NS group. The sensory and motor functions and the state of
      consciousness were assessed at baseline and at predetermined regular intervals.
      Then, the rabbits were continuously observed for 2 weeks to examine the possible
      long-term neurological complications. RESULTS: The sensory blockade onset time,
      motor blockade onset time, and motor blockade duration in the E-isoflurane group
      [1.4 (0.7), 1.6 (0.7), and 34 (10) min, respectively] were similar to those in
      the Lidocaine group [1.3 (0.5), 1.7 (0.8), and 38 (8), min, respectively]. The
      sensory blockade duration in the E-isoflurane group was longer than that in the
      Lidocaine group [68 (13) vs 49 (13) min, P<0.01]. No epidural anaesthetic effects
      occurred in the NS group and the Intralipid group. None of the rabbits showed an
      abnormal consciousness after the epidural drug administration. None of the
      rabbits showed any long-term neurological deficits during a 2 week observation.
      CONCLUSIONS: The present study demonstrates that epidural administration of the
      8% emulsified isoflurane produces completely a reversible epidural anaesthetic
      effect that does not affect the level of consciousness in rabbits.

PMID- 18042559
TI  - Pre-incisional epidural ropivacaine, sufentanil, clonidine, and (S)+-ketamine
      does not provide pre-emptive analgesia in patients undergoing major pancreatic
      surgery.
AB  - BACKGROUND: The concept of pre-emptive analgesia remains controversial. This
      prospective, randomized, and double-blind study compared epidural administration
      of ropivacaine 2 mg ml(-1), sufentanil 0.5 microg ml(-1), clonidine 3 microg ml(
      1), and S(+)-ketamine 0.25 mg ml(-1) (study solution) given before incision with
      the same combination started at the end of the operation. METHODS: After testing
      the stability of the solution using high performance liquid chromatography (HPLC)
      and examining 12 patients for possible side-effects in comparison with the
      epidural infusion of ropivacaine 2 mg ml(-1) and sufentanil 0.5 microg ml(-1), 30
      patients undergoing major pancreatic surgery were recruited into the study.
      Before induction of anaesthesia, an epidural catheter was inserted (TH6-8).
      Patients in Group 1 received a bolus of 8 ml followed by a continuous infusion (8
      ml h(-1)) of the study solution before induction of anaesthesia. In Group 2,
      patients received the same volume of saline before operation, the study solution
      was started at the end of surgery. After operation, the infusion was maintained
      for at least 96 h using a patient-controlled epidural analgesia (PCEA) pump in
      both groups. Patients were evaluated up to the seventh postoperative day for pain
      and side-effects. RESULTS: Visual analogue scale (VAS) values at rest were as
      follows: G1 vs G2: 24 h, 19 (sd 23) vs 6 (13); 48 h, 4 (10) vs 11 (21); and 72 h,
      12 (22) vs 13 (21). VAS values during coughing and mobilization were also
      comparable. Total volume of epidural infusion was 904 (114) ml in G1 vs 892 (154)
      ml in G2. The incidence of side-effects (nausea, vomiting, and motor block) was
      low and not different between the groups. CONCLUSIONS: Pre-incisional epidural
      analgesic infusion did not provide pre-emptive analgesia compared with
      administration started at the end of surgery, but both groups had low pain
      scores.

PMID- 18042561
TI  - Promoting medical innovation while developing sound social and business policy: a
      conversation with Thomas G. Roberts. Interview by Barbara J. Culliton.
AB  - The development of "targeted biologics" as cancer therapy has made the field ripe
      for investment from the private sector and is changing the face of cancer
      medicine, while also raising important policy concerns about price, profit, and
      continued innovation. In this interview Barbara Culliton talks with Thomas
      Roberts, who sees this world from a unique perspective. Roberts, an oncologist,
      has practiced at the Massachusetts General Hospital and is currently thinking
      about innovation as a hedge fund manager.

PMID- 18042562
TI  - Insurers and 'targeted biologics' for cancer: a conversation with Lee N.
      Newcomer. Interview by Barbara J. Culliton.
AB  - New drugs for cancer, targeted at the specific genetic profile of various tumors,
      are revolutionizing cancer therapy, but at a very high cost. Most carry a price
      tag of $50,000 or more per patient per year. Lee Newcomer examines the medical
      and policy issues from his perspective at United Healthcare and from his
      experience as an oncologist. In this interview, Newcomer suggests that all
      patients receiving the targeted biologics be required to participate in a
      clinical trial or an insurance company registry so that data can be collected to
      assure that the right drugs are prescribed for the right patients.

PMID- 18042563
TI  - The intersection of basic science and health policy: a conversation with Victor
      Velculescu. Interview by Barbara J. Culliton.
AB  - Basic scientists should probably focus their attention on medical innovation,
      according to Victor Velculescu, who is part of a group at Johns Hopkins that
      recently discovered 200 new genes related to cancer. Velculescu believes that
      most research scientists probably do not know enough about health policy to play
      a major role in its development. However, as he notes in this interview,
      scientists have an important part to play--indeed, an obligation to explain their
      work and its relevance to legislators and to the general public--because it is
      scientists who can best alert policymakers to what is on the health care horizon.

PMID- 18042564
TI  - Unusual complication after aortic valve replacement.
AB  - We present a report of a postoperative left ventricular-right atrial (LV-RA)
      communication after aortic valve replacement. Such intracardiac defects are rare
      but encountered occasionally after valve surgery. The diagnosis was made by use
      of transesophageal echocardiography with echo-Doppler and color-flow imaging.
      Complications of LV-RA shunts and differential diagnosis are discussed.

PMID- 18042565
TI  - Unusual late presentation of asymptomatic diaphragmatic hernia following
      ventricular assist device explantation.
AB  - The role of left ventricular assist device (LVAD) in treatment options of
      congestive heart failure is becoming more important and the widespread
      application is imminent. There are, however, some serious complications
      associated with LVAD, which make patient management more challenging. We report a
      rare surgical case of asymptomatic diaphragmatic hernia, which was diagnosed 8.5
      years after heart transplantation and LVAD explantation. A left mini (7 cm),
      muscle- and nerve-sparing thoracotomy was performed, and we found the splenic
      flexure of the colon herniated into the left pleural space through a small,
      circumferential defect of the diaphragm ( approximately 4 cm in diameter) created
      for the inflow cannula of LVAD. The hernia was reduced and the defect was
      repaired.

PMID- 18042566
TI  - Necrotizing pneumonitis caused by postoperative pulmonary torsion.
AB  - Pulmonary torsion is an adverse event with a reported incidence of 0.089-0.4%. It
      may occur spontaneously, after trauma but most often as a rare complication after
      pulmonary surgery. We describe a case of lobar torsion of the left upper lobe
      after lobectomy of the left lower lobe, which resulted in a necrotizing
      pneumonitis with fever, hemoptysis and weight loss. A completion pneumonectomy
      was performed after which the patient recovered well. A review of the literature
      shows that a delay in diagnosis and treatment of this rare complication can have
      catastrophic consequences. Surgery is the treatment of choice since sparing of
      the lobe is hardly ever possible due to the irreversible ischemic changes.
      Detorsion, instead of resection, may lead to fatal complications. Although
      infrequent, one should be aware of lobar torsion and the necessity for immediate
      re-intervention.

PMID- 18042567
TI  - Methotrexate pneumonitis precipitated by switching from oral to parenteral
      administration.

PMID- 18042568
TI  - Information-theory based surrogate marker evaluation from several randomized
      clinical trials with continuous true and binary surrogate endpoints.
AB  - BACKGROUND: Surrogate endpoints potentially reduce the duration and/or increase
      the amount of information available in a study, thereby diminishing patient
      burden and cost. They may also increase the effectiveness and reliability of
      research, through beneficial impact on noncompliance and missingness. PURPOSE: In
      this article, we review the meta-analytic approach of Buyse et al. (2000) and its
      extension to mixed continuous and binary endpoints by Molenberghs Geys, and Buyse
      (2001). METHODS: An information-theoretic alternative, based on Alonso and
      Molenberghs (2007a) is proposed. The method is evaluated using simulations and
      application to data from an ophthalmologic trial, with lines of vision lost at 6
      months as candidate surrogate endpoints for lines of vision lost at 12 months.
      The method is implemented as an R function. RESULTS: The information-theoretic
      approach is based on solid theory, easy to apply, and enjoys elegant properties.
      While the information-theoretic approach appears to be somewhat biased downwards,
      this is due to fact that it operates at explicitly observed outcomes, without the
      need for unobserved, latent scales. This is a desirable property. LIMITATIONS:
      While easy-to-use and implement, the theoretical foundation of the information
      theory approach is more mathematical. It produces some bias for small to moderate
      trial/center sizes, and hence is recommended primarily for sufficiently large
      trials. CONCLUSIONS: Since the meta-analytic framework can be computationally
      extremely expensive, the information-theoretic approach of Alonso and Molenberghs
      (2007a) is a viable alternative. For the ophthalmologic case study, the
      conclusion is that the lines of vision lost at sixth month do have some, but not
      overwhelming promise as a surrogate endpoint.

PMID- 18042569
TI  - Monitoring rare serious adverse events from a new treatment and testing for a
      difference from historical controls.
AB  - BACKGROUND: We detail the design of a study to monitor the safety of including
      albendazole to an existing treatment regimen to eliminate lymphatic filariasis.
      We wish to show that this new regimen does not increase the rate of a rare
      serious adverse event (SAE) compared to the old regimen. Controlled but small
      clinical trials have not detected any increase in the SAE using albendazole, and
      it is known to have added benefits; therefore, it is unethical to randomize
      patients to the old regimen. PURPOSE: A sample size for the new regimen is needed
      to test that the new rate of SAE is noninferior to the historic rate. If the new
      regimen does have an inferior rate of SAE then we wish to stop the study early.
      This setup is different from traditional early stopping for efficacy and
      futility. In that traditional case, the two stopping decisions are relative to
      the same null hypothesis of equality, while in our setup, we have two different
      null hypotheses: the noninferiority null and the equality null. When testing the
      former, we need not stop early if the new regimen appears better because no
      subjects are receiving the old regimen anymore anyway. When testing the equality
      of SAE rates, however, we want to stop early if the new regimen has a
      significantly higher rate of SAE. METHODS: We create a design that uses an exact
      difference in proportions test for testing noninferiority, but calculates maximal
      sample size based on conditional power which treats the historical rates as true
      rates. The design allows for early stopping if the new treatment appears inferior
      with respect to SAE rate but makes no corrections for multiple testing. We
      explore the properties of this naive design without assuming the historical rates
      are known. RESULTS: For our example, we show that our naive design strategy
      bounds the type I error of the noninferiority hypothesis in all cases and bounds
      it for the equality hypothesis at 0.05, as long as the true SAE rate is <0.00015.
      The same design has unconditional power for the noninferiority hypothesis greater
      than the nominal 80% as long as the true SAE rate for both regimens are <0.00025.
      LIMITATIONS: The type I and power results above hold only for our historical
      sample size of 17,877. We expect similar type I and power properties to hold with
      studies with SAE rates similar or less (i.e., < 0.00015) and historical sample
      sizes similar or smaller. CONCLUSIONS: Our design for comparing very rare
      historical SAE rates to SAE rates of a new treatment has large power to conclude
      noninferiority of the new treatment SAE rate when both rates are equal, but
      allows early stopping if the new SAE rates are worse.

PMID- 18042570
TI  - Using causal models to show the effect of untestable assumptions on effect
      estimates in randomized controlled trials.
AB  - BACKGROUND: The methods by which randomized controlled trials (RCTs) are analyzed
      rest on several assumptions, most of which are untestable. PURPOSE: To show how
      estimates of the net effect of treatment on survival can be obtained requiring
      only the assumption that randomization produced equivalent groups. METHODS: The
      assumptions underlying ratio measures of effect, based on disease occurrence
      times (DOT) obtained from survival curves, are identified and cumulatively
      removed. RESULTS: The four assumptions usually made are that (1) the ratio of
      disease incidence rates under treatment and under reference exposure is constant
      over time, (2) the groups being compared are exchangeable (equivalent), (3) a
      subject's DOT under treatment is independent of what his DOT would have been
      under the reference exposure, and (4) the treatment effect, if any, is in the
      same direction in all subjects. Removing Assumption 4 leads to an estimator of
      effect resembling the etiologic fraction, but able to accommodate both causative
      and preventive effects. Removing all assumptions but that of exchangeability
      still permits the estimation, directly from the survival curves, of a range of
      effect magnitudes, causative or preventive, compatible with the observed DOTs.
      The exchangeability assumption is the easiest to meet, by randomizing enough
      subjects. LIMITATIONS: The statistical uncertainty that affects the estimates of
      survival probabilities has been ignored. Taking uncertainty into account further
      widens the range of effects compatible with the observations. CONCLUSIONS:
      Retaining only the exchangeability assumption allows for a range of possible
      treatment effects to be estimated, although it may be wide. Readers of RCT
      reports should understand that the determination of a point estimate of effect
      within this range is entirely a function of unverifiable analytic assumptions.

PMID- 18042571
TI  - A comparison of methods for fixed effects meta-analysis of individual patient
      data with time to event outcomes.
AB  - BACKGROUND: Alternative methods for individual patient data (IPD) meta-analysis
      of time-to-event outcomes have been established and utilized in practice. The
      most common approach is a stratified log-rank analysis. The IPD approach is
      considered to be the gold standard approach for meta-analysis and is becoming
      increasingly more popular but the performance of different methods has not been
      studied previously. PURPOSE: To compare commonly used methods for fixed effects
      meta-analysis of individual patient time-to-event data. METHODS: The stratified
      log-rank analysis, an inverse variance weighted average of Cox model estimates,
      and the stratified Cox regression model are compared. First, a theoretical
      comparison of approaches is undertaken. Second, the bias and coverage are
      assessed for the pooled hazard ratio using simulated data under commonly
      encountered meta-analysis conditions. Finally, a comparison is presented using
      empirical data from four separate systematic reviews of anti-epileptic drug
      trials where IPD are available for two time-to-event outcomes. RESULTS: For
      hazard ratio close to 1 with minimal heterogeneity between trials, theoretical
      results suggest similar results should be expected from all the three methods.
      Results for empirical and simulated data are in keeping with the theoretical
      results and show all the three methods perform well under these conditions. When
      there is no heterogeneity and the proportional hazards assumption holds, the
      stratified Cox model and inverse variance weighted average produce similar
      estimates of the pooled treatment effect and are to be preferred to the
      stratified log-rank analysis when the underlying treatment effect is large.
      Coverage values diminish for all the three methods and are below 95% for low or
      moderate heterogeneity. The low coverage values highlight the need for models
      that appropriately account for or explore the between trial variation.
      LIMITATIONS: Until larger simulations can be undertaken, conclusions based on the
      simulated and empirical data should only be applied to small meta-analyses of
      four or five trials. CONCLUSIONS: These investigations suggest that under normal
      conditions all three methods provide similar results. For moderate heterogeneity
      coverage for all the three fixed effects models depreciates.

PMID- 18042572
TI  - Finding family for prospective consent in emergency research.
AB  - BACKGROUND: Innovative approaches are needed to allow for research in the
      emergency setting while not compromising either the rights or the interests of
      the subjects enrolled in such research. The emergency consent exception was
      developed to meet this need. PURPOSE: The goal was to describe the timing of
      initial contact with relatives and the timing of obtaining informed consent for a
      research study in patients with severe traumatic brain injury. METHODS: The study
      was designed as a prospective, observational study of 129 patients enrolled in an
      emergency study of traumatic brain injury conducted under the emergency consent
      exception. Detailed descriptive information was collected both about the
      availability of relatives of patients enrolled in a study of traumatic brain
      injury to give prospective consent within the time period required for entering
      the study and about the extent to which they did give prospective consent during
      that time period. RESULTS: The number of patients with relatives who could be
      contacted by research staff increased with time after injury, with 3% (95% CI=0
      to 6%), 25% (95% CI=18 to 32%), and 43% (95% CI=35 to 52%) having family at 1, 3,
      and 6 h, respectively postinjury. An additional 15% were available within the
      next 6 h. The median time after injury to the initial family contact by the
      research staff was 2.0 h for patients who had relatives already present at the
      hospital and 5.7 h for patients whose family had already been contacted by the
      hospital. The percentage of family members actually giving prospective research
      consent was much smaller; only 18% actually gave prospective consent within 6 h
      postinjury. The proportion of critically ill patients with family available to
      give prospective consent for enrollment in emergency research studies depends
      primarily on the time period allowed for enrollment in the individual study and
      the length of the transition from initial contact to completed prospective
      consent. LIMITATIONS: The study was performed in a specific patient population
      and may not be generalizable to other settings. CONCLUSIONS: Careful attention
      should be paid by investigators and IRBs as to whether the emergency consent
      exception is really required for a particular study, or whether the study could
      proceed using only prospective consent with a longer recruitment period, more
      research sites, and a higher yield of available family members giving prospective
      consent. Measures that could shorten the time between initial contact and
      obtaining informed consent (for example, allowing consent over the phone rather
      than requiring written consent) might decrease the need for the emergency consent
      exception.

PMID- 18042573
TI  - Quality assurance questionnaire for professionals fails to improve the quality of
      informed consent.
AB  - BACKGROUND: The informed consent process for research warrants improvement but
      approaches designed to enhance informed consent need testing in the context of
      actual clinical research. PURPOSE: Test the cumulative effect of a retrospective
      quality assurance questionnaire intended to enhance awareness in the person
      obtaining informed consent on the quality of the informed consent in clinical
      trials. METHODS: In the Veterans Affairs Cooperative Study 'Enhancing the Quality
      of Informed Consent- Self Monitoring', 30 study sites are randomly assigned from
      five clinical trials to either use a new quality assurance questionnaire after
      each informed consent encounter or the standard process of obtaining informed
      consent. The quality of informed consent is evaluated using independent telephone
      interviews of 836 subjects who had given consent to participate in the clinical
      trials and the authors' study. The main outcome measures are two previously
      validated scores derived from an independent telephone interview, measuring the
      overall quality of consent as well as the degree of 'therapeutic
      misapprehension'. Patients and assessors are blind to the study arm assignment.
      RESULTS: Subjects report complete (93%) or some (6%) satisfaction with the
      consent process of the 'parent' clinical trial, and 91% recognize no consequences
      to non-participation. Concerning the 'primary purpose' of the parent trial, 67%
      indicate understanding of the research purpose, 41% that the research is to
      benefit others, while 14% think the research is directed to their own benefit;
      60% report no risk to participation and 65% report at least one expects direct
      benefit. Interviewers assess 77% of subjects as showing full appreciation of the
      'voluntariness' of participation. The quality assurance questionnaire do not
      provide an appreciable effect on the quality of informed consent. Using mixed
      model methods to account for the group randomization, near zero, non-significant
      effects have been found for the overall assessment score (-0.034 on a 0-10 point
      scale, standard error 0.099, P = 0.73) and for the score measuring 'therapeutic
      misconception' (-0.005 on a 0-5 point scale, standard error 0.137, P = 0.97).
      Permutation methods yield similar results. Confidence intervals are narrow enough
      to exclude any clinically important effect. LIMITATIONS: The intervention may
      work in a more homogeneous patient population, or one that is not sampled. The
      outcome measurement relies on a short, anonymous, telephone interview (to
      minimize burden and eliminate bias), but a longer, face-to-face interview may be
      more sensitive to differences. A 'checklist' tied directly to the outcome
      measures may show an effect. CONCLUSIONS: Despite prior beliefs, a standardized
      quality assurance tool do not enhance informed consent in actual clinical trials.
      Future research is needed to rigorously evaluate proposed methods to enhance
      informed consent prior to widespread introduction.

PMID- 18042574
TI  - The Veterans Affairs Low Vision Intervention Trial (LOVIT): design and
      methodology.
AB  - BACKGROUND: Visual impairment is a major public health problem. Vision
      rehabilitation programs have the potential to restore independence and improve
      quality of life for persons with permanent vision loss, and few have been
      evaluated in randomized controlled trials. PURPOSE: The Veterans Affairs (VA) Low
      Vision Intervention Trial is a multicenter randomized clinical trial to evaluate
      the effectiveness of a new outpatient low vision rehabilitation program. METHODS:
      126 patients with moderate and severe vision loss due to macular diseases are
      randomized to low vision treatment in an outpatient setting or a usual care
      control group at two VA facilities in Hines, Illinois, and Salisbury, North
      Carolina. The primary outcome is the change in visual reading ability from
      baseline to four months measured with the Veterans Affairs Low Vision Visual
      Functioning Questionnaire-48 (VA LV VFQ-48). Secondary outcomes compare the mean
      change in visual ability measured with the VA LV VFQ-48 (overall ability,
      mobility, visual information processing, visual motor skills) for the treatment
      and control groups. Costs and cost effectiveness of outpatient treatment are
      evaluated. RESULTS: The low vision rehabilitation setting, use of a waiting list
      control group to address ethical issues, development of the treatment protocol,
      development of a vision function questionnaire for patients to self-report the
      difficulty they experience performing daily activities, and the use of Rasch
      analysis to develop and estimate this outcome measure are described. LIMITATIONS:
      If the new low vision rehabilitation program is proven effective, studies will be
      needed to determine which of the multiple aspects of the intervention are
      necessary and sufficient. CONCLUSIONS: The challenges of conducting clinical
      trials in a rehabilitation setting and use of a waiting list (deferred treatment)
      control group extend beyond LOVIT. The design and methods of LOVIT may be
      applicable to other trials of rehabilitation services and to outcomes for which
      reliable and valid measurement tools must be developed.

PMID- 18042578
TI  - Precautionary principle for toxic chemicals - no alternative to safeguard
      societal benefits.

PMID- 18042575
TI  - Design of the PEDS-C trial: pegylated interferon +/- ribavirin for children with
      chronic hepatitis C viral infection.
AB  - BACKGROUND: PEDS-C is the first multicenter placebo-controlled trial for the
      treatment of chronic hepatitis C (HCV) in childhood that has ever been conducted
      in the United States (USA). Establishment of the research team, protocol,
      administrative infrastructure, and ancillary contributors for the pediatric trial
      took years of planning. PURPOSE: To study the safety and efficacy of pegylated
      interferon alpha (PEG-2a) plus ribavirin (RV) with PEG-2a monotherapy in children
      aged 5 years through 18 years. To assess the health-related quality of life and
      growth and body composition in children with chronic hepatitis C infection,
      before, during, and after treatment. METHODS: Eleven centers of pediatric
      hepatobiliary clinical research were united in a National Institutes of Diabetes
      and Digestive and Kidney Diseases (NIDDK) funded grant with financial support
      from the Food and Drug Administration (FDA) and a corporate sponsor to conduct
      the treatment trial. LIMITATIONS: The most important initial limitation in the
      design of this complex study was securing the financial support and
      infrastructural organization, a process that took several years. Challenges faced
      by the study group included identifying the optimal study design given the
      limited study population, and determining what ancillary studies could be
      incorporated into the treatment trial. CONCLUSIONS: In this article the process
      taken to design the study and administrative infrastructure, the lessons learned,
      and the controversial issues deliberated during the planning process are
      discussed. The evolution of the study and the considerations taken in the
      development of the protocol are valuable tools which can be applied to pediatric
      clinical trials in general.

PMID- 18042579
TI  - Precaution, institutions, incentives, heuristics, regulation and hormesis:
      comments on 'Hormesis in precautionary regulatory culture: models preferences and
      the advancement of science'.

PMID- 18042580
TI  - Hormesis in precautionary regulatory culture: models preferences and the
      advancement of science.
AB  - The article focuses on flaws in the actual approaches of exposure to a chemical
      of recipient organisms. It demonstrates the excessive use of arguments based on
      adverse effects and underlines the necessity to take adaptive effects seriously.
      Regulators are invited to rethink their inclination to the 'When in doubt, keep
      it out.' precautionary approach, with results in counter-productive and costly
      regulations. The authors are clear about the necessity to include hormesis, in
      the form of a toxicological insignificant exposure (TIE) level, related to the
      concentration, as a regulatory translation of adaptive effects. This inclusion
      might well be the 'brake' for the looming 'collision' with reality of the actual
      linear toxicological models. This analysis includes the advice to EPA, not to
      follow the 'witch hunt of synthetic chemicals' as embodied in the EU REACH
      program.

PMID- 18042582
TI  - Hormesis and precaution: the twain shall meet.
AB  - Regulatory focus on quantifying risk of disease or death from exposure to
      hazardous substances via monotonic dose-response models has downplayed or even
      rejected potential benefits to human health from exposures to low (sub-threshold)
      doses, and thus represented by either U-shaped or J-shaped models. On the other
      hand, most environmental health policy hypothesizes, without firm evidence, that
      cancer risk is proportional to exposure at low doses of current ambient
      exposures. An acceptable exposure is determined by either setting a somewhat
      arbitrary ;acceptable' level of risk, such as one in a million excess individual
      lifetime cancer risk or, in the case of several types of animal toxicological
      test results, applying multiplicative safety factors to a specific concentration,
      generally derived from a benchmark dose or NOAEL. This seemingly precautionary
      approach is questionable in light of much experimental evidence indicating
      protective effects of exposure at low doses - U-shaped or J-shaped models. We
      demonstrate that incorporating the possibility of hormesis into regulatory
      decision-making is precautionary, while use of default results in policy
      conflicts with precaution.

PMID- 18042583
TI  - Lack of a role for creatine phosphate kinase in sulphur mustard-induced
      cytotoxicity.
AB  - Several compounds involved in the creatine phosphate kinase (CPK) pathway were
      evaluated for their protective effects against the chemical warfare (CW) agent
      sulphur mustard (HD), in primary chick embryo neuron and first passage human skin
      keratinocyte cultures. High concentrations of both creatine and creatine
      phosphate were found to be protective under all culture conditions and increased
      the LC(50) of HD in both culture systems up to approximately 250%. Little
      difference was observed in the protective activity of these compounds in
      undifferentiated versus differentiated neuronal culture, or in proliferating
      versus differentiating cultures of keratinocytes. The protective effect of these
      compounds was found to be strictly prophylactic in nature. Although a modest
      decline in HD half-life was measured in buffer containing creatine phosphate,
      this did not account for the protective effects of this compound. In contrast to
      historical literature reporting 90-100% HD-induced CPK inhibition of purified
      enzyme, less than 30% of CPK activity was found to be inhibited by HD in both
      human keratinocytes and in swine blood plasma. Incubation of keratinocyte
      cultures with creatine or creatine phosphate prior to HD exposure did not alter
      CPK activity, compared with HD-only treated cultures. Although high mM
      concentrations of both creatine and creatine phosphate exert significant
      protective effects against HD, these results do not support a role for CPK in its
      toxicity or in the development of medical countermeasures against this CW agent.

PMID- 18042584
TI  - Exploring DNA damage responses in human cells with recombinant adenoviral
      vectors.
AB  - Recombinant adenoviral vectors provide efficient means for gene transduction in
      mammalian cells in vitro and in vivo. We are currently using these vectors to
      transduce DNA repair genes into repair deficient cells, derived from xeroderma
      pigmentosum (XP) patients. XP is an autosomal syndrome characterized by a high
      frequency of skin tumors, especially in areas exposed to sunlight, and,
      occasionally, developmental and neurological abnormalities. XP cells are
      deficient in nucleotide excision repair (affecting one of the seven known XP
      genes, xpa to xpg) or in DNA replication of DNA lesions (affecting DNA polymerase
      eta, xpv). The adenovirus approach allows the investigation of different
      consequences of DNA lesions in cell genomes. Adenoviral vectors carrying several
      xp and photolyases genes have been constructed and successfully tested in cell
      culture systems and in vivo directly in the skin of knockout model mice. This
      review summarizes these recent data and proposes the use of recombinant
      adenoviruses as tools to investigate the mechanisms that provide protection
      against DNA damage in human cells, as well as to better understand the higher
      predisposition of XP patients to cancer.

PMID- 18042585
TI  - Atherosclerosis and lupus: the SLICC Study.

PMID- 18042586
TI  - Distinguished effects of antiphospholipid antibodies and anti-oxidized LDL
      antibodies on oxidized LDL uptake by macrophages.
AB  - Several interpretations have been made regarding the specificity of
      antiphospholipid antibodies and antibodies against oxidized low-density
      lipoprotein (oxLDL), but these are still controversial. In the present study, we
      delineated specificity of these two types of antibodies and analyzed their
      regulatory effect on oxLDL and/or beta( 2)-glycoprotein I (beta(2)GPI) binding to
      macrophages. Scavenger receptor-mediated binding of oxLDL (or its beta(2)GPI
      complexes) to macrophages was observed and the binding was partly prevented by
      beta( 2)GPI. The IgG monoclonal anti-beta(2)GPI antibody (WB-CAL-1), which was
      derived from NZW x BXSB F1 mouse (a model of antiphospholipid syndrome),
      significantly increased the oxLDL/beta(2)GPI binding to macrophages. In contrast,
      IgM anti-oxLDL natural antibody, EO6 (derived from apoe( -/-) mouse), prevented
      the binding. Different antigenic specificity of these antibodies to oxLDL and its
      beta(2)GPI complexes was also confirmed in TLC-ligand blot and ELISA. Thus, IgG
      anti-beta(2) GPI autoantibodies contribute to lipid metabolism (housekeeping of
      oxLDL by macrophages) whereas IgM natural anti-oxLDL antibodies may protect
      against atherogenesis. In addition, in vitro data suggest that relatively high
      dose of intravenous immunoglobulin preparations (mainly contain IgG anti-oxLDL
      antibodies) might also prevent atherogenesis by inhibiting the oxLDL binding to
      macrophages.

PMID- 18042587
TI  - Microarray analysis of microRNA expression in peripheral blood cells of systemic
      lupus erythematosus patients.
AB  - MicroRNAs (miRNAs) are noncoding RNA molecules of 21-24 nt that regulate the
      expression of target genes in a post-transcriptional manner. Evidence indicates
      that miRNAs play essential roles in embryogenesis, cell differentiation and
      pathogenesis of human diseases. This study describes a comparison between the
      miRNA profile of the systemic lupus erythematosus (SLE) patients and the controls
      to develop further understanding of the pathogenesis of SLE. Peripheral blood
      mononuclear cells were isolated from blood samples of 23 SLE patients, 10
      idiopathic thrombocytopenic purpura patients and 10 healthy controls. The miRNA
      microarray chip analysis identified 16 miRNAs differentially expressed in SLE.
      The chip results were confirmed by northern blot analysis. This work indicates
      that miRNAs are potential diagnosis biomarkers and probable factors involved in
      the pathogenesis of SLE.

PMID- 18042588
TI  - Role of distinct immune components in the radiation-induced abrogation of
      systemic lupus erythematosus development in mice.
AB  - The New Zealand Black x New Zealand White F1 [(NZB/NZW) F1] mouse develops an
      autoimmune condition resembling aspects of human systemic lupus erythematosus
      (SLE). We investigated the effects of a novel prophylactic thoraco-abdominal
      gamma irradiation protocol on the onset and evolution of lupus in these animals.
      Survival of irradiated mice was higher when compared with nonirradiated mice.
      Kidney lesions were milder and autoantibody levels were lower in irradiated mice.
      To identify possible mechanisms involved in the radiation-induced improvement of
      disease, distinct components of humoral and cellular immune responses were
      evaluated. Because B-1 cells are known to be involved in various autoimmune
      diseases, we investigated the participation of these cells in SLE progression.
      Unexpectedly, B-1 cells were not depleted in (NZB/NZW) F1, even after several
      rounds of irradiation. No alterations were found in viability and physiology of B
      1 cells in SLE animals with the exception of constitutive overexpression of the
      anti-apoptotic molecule Bcl-2, which may account for the observed
      radioresistance. Thus, a role for B-1 cells in murine SLE cannot be excluded,
      since the irradiation protocol did not effectively eliminate these cells.
      Additionally, we demonstrate a marked delay in the ability of splenocytes to
      repopulate the spleen after irradiation in (NZB/NZW) F1, in contrast to
      leucocytes in other cellular compartments. The implications of these findings for
      the fate of SLE in this model are discussed.

PMID- 18042589
TI  - Telomere length analysis in monocytes and lymphocytes from patients with systemic
      lupus erythematosus using multi-color flow-FISH.
AB  - In order to analyse telomere length in subsets of human peripheral blood
      lymphocytes and monocytes, we modified a recently developed multicolor flow-
      fluorescent in situ hybridization (FISH) methodology that combines flow-FISH and
      antibody staining for cell surface antigens. We analysed telomere length of
      peripheral blood mononuclear cells in a group of 22 patients with systemic lupus
      erythematosus (SLE) and 20 age-matched healthy donors. We found that neither
      CD4+, CD8+, CD19+ cells nor CD14+ monocytes have significantly shorter telomeres
      compared with their healthy counterparts. On the basis of these findings, we then
      used monocyte telomere length as internal reference in order to control for intra
      individual variability in telomere length. By using this approach, we could
      demonstrate significant telomere shortening in all three lymphocyte subsets (in
      all cases P < 0.05) compared with monocytes. However, these differences did not
      vary significantly between SLE patients and controls. In summary, telomere
      lengths in subpopulations of hematopoietic cells can be monitored in patients
      with SLE using multicolor flow-FISH. While confirming data by other groups on
      telomere length in lymphocyte subpopulations, our data argue against an increased
      proliferation rate of peripheral blood monocytes reflected by accelerated
      telomere shortening in patients with SLE.

PMID- 18042590
TI  - Neurometabolic changes in normal white matter may predict appearance of
      hyperintense lesions in systemic lupus erythematosus.
AB  - To determine if neurometabolic changes in the white matter (WM) of systemic lupus
      erythematosus (SLE) patients may predict the appearance of small hyperintense
      lesions on T2-weighted magnetic resonance imaging (MRI) inside the magnetic
      resonance spectroscopy (MRS) region of interest (ROI). We included 30 SLE
      patients and 23 controls. We performed single voxel proton MRS over the superior
      posterior region of the corpus callosum. We measured signals from N-acetyl
      compounds (NAA), choline (Cho) and creatine-phosphocreatin (Cr) and determined
      NAA/Cr and Cho/Cr ratios. After a minimum of 12 months, MRI and MRS were repeated
      in all patients and nine volunteers. Twenty patients had normal MRI and 10
      patients had MRI hyperintense lesions in the MRS ROI at baseline. All patients
      had hyperintense lesions in the MRS ROI in follow-up MRIs. All SLE patients had
      increased Cho/Cr values at both MRS when compared with normal controls (P =
      0.001). In addition, there was an increase in Cho/Cr values when patients'
      baseline and follow-up MRS were compared (P = 0.001). We observed a correlation
      between Cho/Cr ratios and number of WM lesions (r = 0.69; P = 0.001). Increased
      Cho/Cr in normal appearing WM may be indicative of future appearance of
      hyperintense T2-weighted MRI lesions in SLE patients.

PMID- 18042591
TI  - Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis:
      rationale and protocol for the randomized, controlled Aspreva Lupus Management
      Study (ALMS).
AB  - The Phase III Aspreva Lupus Management Study (ALMS) will investigate
      mycophenolate mofetil (MMF) therapy for lupus nephritis (LN). Eligibility
      criteria include: 12-75 years of age; diagnosis of systemic lupus erythematosus
      according to revised American College of Rheumatology criteria; and biopsy
      demonstrated LN (Class III-V). Randomized patients will receive open-label
      induction therapy with MMF or cyclophosphamide in combination with
      corticosteroids for 24 weeks. The primary efficacy endpoint is treatment response
      [decreased proteinuria and stabilized (within 25% of baseline) or improved serum
      creatinine level]. Patients achieving response or complete remission
      (normalization of all parameters) will be rerandomized to double-blind, placebo
      controlled maintenance treatment with MMF or azathioprine, both plus
      corticosteroids. The maintenance phase primary endpoint is time to treatment
      failure. To detect a 15% rate improvement in the MMF group compared with
      cyclophosphamide, and to provide 90% power, a total of 358 patients will be
      required for the induction phase. On the basis of a projected 278 rerandomized
      patients, the maintenance phase will have 90% power to detect a difference
      between treatment groups assuming azathioprine and MMF three-year failure rates
      of 59.5% and 40.7%, respectively. Aspreva Lupus Management Study may provide
      invaluable comparative data on the efficacy and safety of MMF as LN induction and
      maintenance therapy.

PMID- 18042592
TI  - Aspirin therapy and thromboxane biosynthesis in systemic lupus erythematosus.
AB  - Incomplete suppression of thromboxane biosynthesis during aspirin therapy is
      associated with increased cardiovascular risk. Since systemic lupus erythematosus
      (SLE) is associated with platelet activation and increased cardiovascular
      mortality, we compared thromboxane and prostacyclin biosynthesis in patients with
      SLE and control subjects, and measured inhibition of thromboxane excretion in
      aspirin-treated subjects. We measured the urinary excretion of 11-dehydro
      thromboxane B( 2) (TXB(2)) and 2,3-dinor 6-ketoPGF(1alpha) (PGI-M), the stable
      metabolites of thromboxane A(2) and prostacyclin, respectively, in 74 patients
      with SLE and 70 controls. In subjects who were not receiving aspirin, TXB(2)
      excretion was higher in patients with SLE [0.40 ng/mg creatinine (0.26-0.64),
      median (interquartile range)] than controls [0.31 ng/mg creatinine (0.23-0.44)]
      (P = 0.04), and in these patients, TXB(2) excretion correlated with disease
      activity (rho = 0.28, P = 0.03) and tumor necrosis factor alpha (rho = 0.48, P <
      0.001). Aspirin therapy resulted in significantly lower TXB(2) excretion in
      controls (P = 0.01), but not in patients with SLE (P = 0.10), compared with
      subjects not receiving aspirin. Prostacyclin biosynthesis did not differ among
      patients and controls, and was not affected by aspirin (P all >0.35). Thromboxane
      biosynthesis is increased in SLE and is associated with disease activity.
      Additionally, response to aspirin may be attenuated in some patients with SLE.

PMID- 18042593
TI  - Sensorineural dysacusis in patients with systemic lupus erythematosus.
AB  - The objective of this study was to establish the frequency of involvement of the
      auditory apparatus in 45 female patients with systemic lupus erythematosus (SLE)
      submitted to general clinical and laboratory assessments, and tone and vocal
      audiometry accompanied by a questionnaire evaluating auditory symptoms. The
      control group consisted of 45 healthy women, matched by age. Auditory symptoms
      were present in 25 (55.5%) patients, with a diagnosis of sensorineural hearing
      loss in seven (15.6%) patients. A significant correlation with hypoacusis (P <
      0.001), ear fullness (P = 0.012) and tinnitus (P = 0.017) was observed in
      patients with hearing loss. None of the clinical or laboratory parameters showed
      an association with sensorineural hearing loss. In the control group, three women
      (6.7%) presented audiometric alterations, including two with altered tympanometry
      results and one with mild sensorineural hearing loss. In conclusion, an adequate
      investigation of auditory symptoms is important during the follow-up of patients
      with SLE, since manifestations of the auditory apparatus and sensorineural
      hearing loss can affect a significant proportion of patients.

PMID- 18042594
TI  - Rare association of multiple sclerosis and systemic lupus erythematosus.
AB  - Although both multiple sclerosis (MS) and systemic lupus erythematosus (SLE) are
      relatively common autoimmune disorders, especially in young women and often
      coexist in families, they are only rarely reported to coexist in a single
      patient. We here present a case of a young woman with a history of MS from many
      years who diagnosed as suffering as well from SLE.

PMID- 18042595
TI  - Cutaneous alternariosis in a patient with systemic lupus erythematosus.
AB  - Alternaria species are common saprophytic fungi that naturally subsist on
      decaying plant materials, and occasionally may cause diseases in human beings and
      domestic animals. They can be a potential opportunistic pathogen in
      immunocompromized hosts or those with significant underlying disease. However,
      rarely they are also pathogen in otherwise healthy hosts. We report here the
      first case of cutaneous alternariosis in a 30-year-old woman who was on systemic
      steroid therapy for active systemic lupus erythematosus. The patient was referred
      to our department with purple papules and ulcerated nodules on the dorsum of the
      hands, wrists and ankles. Skin biopsy showed granulomatous reaction with fungal
      elements that were subsequently identified as Alternaria species. Individual
      lesions were successfully treated with oral itracanozole 200mg daily for six
      weeks. Besides the patient's own disease, the use of systemic steroid use might
      be a possible predisposing factor for the development of cutaneous alternariosis.

PMID- 18042596
TI  - Disease activity, damage and survival in Mexican patients with acute severe
      systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a clinical syndrome of varying severity.
      Although the survival and prognosis of SLE have steadily improved, there is a
      group of patients who present an acute fatal outcome despite aggressive therapy.
      We designed this study to evaluate the factors associated with mortality in
      patients with acute severe SLE. During 2004-06, 41 Mexican SLE patients that
      could not be managed in the out-patient clinic and with acute severe major organ
      system involvement [nephritis, severe thrombocytopenia (platelet count below 20
      000 per microL) acute neuropsychiatric pulmonary, gastrointestinal or cardiac
      disease and generalized vasculitis] were studied. During the first admission,
      disease activity (SLE Disease Activity Index (SLEDAI), SLE Activity Measured),
      damage [SLE International Collaborating Clinics (SLICC)], and therapy were
      assessed. Survival using Kaplan-Meier curves, odd ratios with 95% confidence
      interval and logistic regression analysis were used to determine risk factors for
      mortality. Ninety percent were female with a mean age of 29 +/- 19 years and mean
      disease duration of 21 +/- 9 months. The principal causes of first admission were
      renal (27%), SNC (22%) and cardiopulmonary (15%). After a mean follow-up of 9.7
      +/- 6 months, 16 (39%) patients died. Deceased patients had significantly higher
      SLEDAI (P = 0.004), and SLICC (P = 0.03) scores. The manifestations associated
      with mortality were renal disease activity (odds ratio, OR 4.6, confidence
      interval, CI 95% 1.0-20.6), infections (OR 3.2 CI 95% 2.0-5.3) and
      thrombocytopenia (OR 4.0, CI 95% 1.0-15.9). The survival at 9.7 months was 72, 62
      and 50% in patients with an SLEDAI score of 3-10, 11-20 and > or =21,
      respectively. The SLEDAI score, the presence of damage and infection were
      associated with death in patients with acute severe SLE.

PMID- 18042597
TI  - Aortic dissection in a case of systemic lupus erythematosus.

PMID- 18042598
TI  - Thrombotic microangiopathy in an adult patient with clinically amyopathic
      dermatomyositis complicated with interstitial lung disease.

PMID- 18042599
TI  - Childhood hermolytic uremic syndrome associated with systemic lupus
      erythematosus.

PMID- 18042600
TI  - Late onset systemic lupus erythematosus: a new approach.

PMID- 18042601
TI  - Challenging assumptions about rehabilitation.

PMID- 18042602
TI  - Tilted seat position for non-ambulant individuals with neurological and
      neuromuscular impairment: a systematic review.
AB  - OBJECTIVE: To determine the effects of tilt-in-space seating on outcomes for
      people with neurological or neuromuscular impairment who cannot walk. DATA
      SOURCES: Search through electronic databases (MEDLINE, Embase, CINAHL, AMED).
      Discussions with researchers who are active in field. REVIEW METHODS: Selection
      criteria included interventional studies that investigated the effects of seat
      tilt on outcome or observational studies that identified outcomes for those who
      had used tilt-in-space seating in populations with neurological or neuromuscular
      impairments. Two reviewers independently selected trials for inclusion, assessed
      quality and extracted data. RESULTS: Nineteen studies were identified which
      fulfilled the selection criteria. Seventeen of these were essentially before
      after studies investigating the immediate effects of tilting the seating. All
      studies looked at populations with neurological impairment, and most were on
      children with cerebral palsy (n=8) or adults with spinal cord injury (n=8).
      REVIEWER'S CONCLUSION: Posterior tilt can reduce pressures at the interface under
      the pelvis.

PMID- 18042603
TI  - Effects of modified constraint-induced movement therapy on reach-to-grasp
      movements and functional performance after chronic stroke: a randomized
      controlled study.
AB  - OBJECTIVE: To evaluate changes in (1) motor control characteristics of the
      hemiparetic hand during the performance of a functional reach-to-grasp task and
      (2) functional performance of daily activities in patients with stroke treated
      with modified constraint-induced movement therapy. DESIGN: Two-group randomized
      controlled trial with pretreatment and posttreatment measures. SETTING:
      Rehabilitation clinics. SUBJECTS: Thirty-two chronic stroke patients (21 men, 11
      women; mean age=57.9 years, range=43-81 years) 13-26 months (mean 16.3 months)
      after onset of a first-ever cerebrovascular accident. INTERVENTION: Thirty-two
      patients were randomized to receive modified constraint-induced movement therapy
      (restraint of the unaffected limb combined with intensive training of the
      affected limb) or traditional rehabilitation for three weeks. MAIN MEASURES:
      Kinematic analysis was used to assess motor control characteristics as patients
      reached to grasp a beverage can. Functional outcomes were evaluated using the
      Motor Activity Log and Functional Independence Measure. RESULTS: There were
      moderate and significant effects of modified constraint-induced movement therapy
      on some aspects of motor control of reach-to-grasp and on functional ability. The
      modified constraint-induced movement therapy group preplanned reaching and
      grasping (P=0.018) more efficiently and depended more on the feedforward control
      of reaching (P=0.046) than did the traditional rehabilitation group. The modified
      constraint-induced movement therapy group also showed significantly improved
      functional performance on the Motor Activity Log (P<0.0001) and the Functional
      Independence Measure (P=0.016). CONCLUSIONS: In addition to improving functional
      use of the affected arm and daily functioning, modified constraint-induced
      movement therapy improved motor control strategy during goal-directed reaching, a
      possible mechanism for the improved movement performance of stroke patients
      undergoing this therapy.

PMID- 18042604
TI  - Patterns of postural deformity in non-ambulant people with cerebral palsy: what
      is the relationship between the direction of scoliosis, direction of pelvic
      obliquity, direction of windswept hip deformity and side of hip dislocation?
AB  - OBJECTIVE: To investigate: (a) associations between the direction of scoliosis,
      direction of pelvic obliquity, direction of windswept deformity and side of hip
      subluxation/ dislocation in non-ambulant people with cerebral palsy; and (b) the
      lateral distribution of these postural asymmetries. DESIGN: Cross-sectional
      observational study. SETTING: Posture management services in three centres in the
      UK. SUBJECTS: Non-ambulant people at level five on the gross motor function
      classification system for cerebral palsy. MAIN MEASURES: Direction of pelvic
      obliquity and lateral spinal curvature determined from physical examination,
      direction of windswept hip deformity derived from range of hip
      abduction/adduction, and presence/side of unilateral hip subluxation defined by
      hip migration percentage. RESULTS: A total of 747 participants were included in
      the study, aged 6-80 years (median 18 years 10 months). Associations between the
      direction of scoliosis and direction of pelvic obliquity, and between the
      direction of windswept hip deformity and side hip subluxation/dislocation were
      confirmed. A significant association was also seen between the direction of
      scoliosis and the direction of the windswept hip deformity (P<0.001) such that
      the convexity of the lateral spinal curve was more likely to be opposite to the
      direction of windsweeping. Furthermore, significantly more windswept deformities
      to the right (P=0.007), hips subluxed on the left (P=0.002) and lateral
      lumbar/lower thoracic spinal curves convex to the left (P=0.03) were observed.
      CONCLUSIONS: The individual asymmetrical postural deformities are not unrelated
      in terms of direction and not equally distributed to the left/right. A pattern of
      postural deformity was observed.

PMID- 18042605
TI  - Including children in family-focused acquired brain injury rehabilitation: a
      national survey of rehabilitation staff practice.
AB  - OBJECTIVE: To establish whether rehabilitation staff work regularly with child
      relatives of adults with acquired brain injury to involve them in their family
      member's rehabilitation. To explore factors influencing rehabilitation staff's
      decisions about involving child relatives. DESIGN: A cross-sectional postal
      survey design was used for the main study. Questionnaire packs were sent to
      rehabilitation staff, followed by a reminder letter one week later. Non
      responders received a follow-up pack after three weeks.A prospective design was
      used with a subsample of participants who re-completed the questionnaire one
      month later. SUBJECTS: Participants were 393 multidisciplinary staff working in
      rehabilitation services for adults with acquired brain injury throughout the UK.
      MAIN MEASURES: A questionnaire based on the theory of planned behaviour was
      designed specially for the purposes of the study. RESULTS: A response rate of 67%
      (n=263) was obtained. Few respondents (19%, n=50) reported carrying out work with
      child relatives. Perceived behavioural control (e.g. access to training,
      resources and support) significantly predicted staff's intention to work with
      child relatives, and whether they carried this out. Staff's attitudes towards
      work with child relatives also significantly predicted intentions. Other
      influential factors were anxiety, training, work setting and perceptions of
      colleagues' attitudes. CONCLUSIONS: Little work is carried out with child
      relatives by acquired brain injury rehabilitation staff, influenced by several
      factors. A priority in addressing this is to provide staff training.

PMID- 18042606
TI  - Relationship between aerobic fitness and quality of life in female fibromyalgia
      patients.
AB  - OBJECTIVE: To determine whether there is a direct link between quality of life
      and aerobic capacity among female fibromyalgia patients. DESIGN: Cross-section
      study. SETTING: University of Leon. SUBJECTS: Twenty-nine women belonging to the
      Leon Fibromyalgia and Chronic Fatigue Association. MAIN MEASUREMENTS: Aerobic
      capacity and quality of life were measured by means of the Six-Minute Walk Test
      and the Fibromyalgia Impact Questionnaire. Outcome measures included heart rate
      and rate of perceived fatigue and dypsnoea. RESULTS: The average distance walked
      was 432.8 (61.2) m and the total average Fibromyalgia Impact Questionnaire score
      was 47.5 (18.9). Only item 1 of the Fibromyalgia Impact Questionnaire, physical
      function, showed any statistically significant link with the distance walked,
      which had no statistically significant relationship with any of the variables
      studied. CONCLUSION: The physical fitness of women with fibromyalgia, as
      determined by the Six-Minute Walk Test and the Fibromyalgia Impact Questionnaire,
      has no direct relation with quality of life as the patients perceive it.

PMID- 18042607
TI  - Usefulness of the Elderly Mobility Scale for classifying residential placements.
AB  - BACKGROUND AND PURPOSE: To investigate the factor structure and cut-off scores of
      the Elderly Mobility Scale for making placement decisions in extended care
      settings. SUBJECTS: Ninety elderly residents of mean ages ranging from 79.0 to
      86.4 years were recruited from homes for the aged (OAH group), and care and
      attention homes with or without supplemental infirmary care (IS and non-IS
      groups, respectively). METHODS: The Elderly Mobility Scale was administered to
      all the residents by five trained practising physiotherapists. RESULTS: Factor
      analysis revealed a two-factor structure, with two items into a bed mobility
      subscale and the other five items into a functional mobility subscale.
      Significant differences were found in the residents' Elderly Mobility Scale
      scores among the OAH, non-IS and IS groups. The accuracy of the three cut-off
      scores based on the five functional mobility items reached 90% for classifying
      the residents into different placements. DISCUSSION AND CONCLUSION: The findings
      suggested that Elderly Mobility Scale scores can be better interpreted with the
      'bed mobility' and 'functional mobility' subscales. The high accuracy of
      classification based on the cut-off scores reflects a good item and construct
      match of the Elderly Mobility Scale. Our findings support the usefulness of the
      Elderly Mobility Scale for residential placement of elderly people, which can be
      generalized to residential settings and post-discharge plans similar to those
      used in this study.

PMID- 18042608
TI  - Rehabilitation of decreased motor performance in patients with chronic fatigue
      syndrome: should we treat low effort capacity or reduced effort tolerance?
AB  - AIM: The aetiology, pathophysiology, diagnostic delineation and treatment of
      chronic fatigue syndrome (CFS) remain a matter of debate. Here some aspects of
      the debate are elucidated, with a particular focus on the patients' decreased
      motor performance. HYPOTHESIS: The pathophysiological basis of decreased motor
      performance in CFS may, theoretically, involve three components: (1) a peripheral
      energetic deficit (impaired oxidative metabolism and/or physical deconditioning);
      (2) a central perceptual disturbance (higher effort sense or increased
      'interoception'); and (3) a fundamental failure of the neurobiological stress
      system, leading to an abnormal 'sickness response'. It is proposed that the first
      two components may lead to low effort capacity, while the third component may
      lead to reduced effort tolerance. Although there is evidence for low effort
      capacity influencing symptoms and functional limitations in CFS, it is assumed
      that reduced effort tolerance might be the primary disturbance in CFS. DIAGNOSTIC
      IMPLICATIONS: Distinguishing low effort capacity and reduced effort tolerance may
      contribute to a refinement of current diagnostic criteria of CFS and the
      identification of subgroups. THERAPEUTIC IMPLICATIONS: The above-mentioned
      distinction may make it possible to formulate a rationale for an effective
      implementation and adequate outcome evaluation of rehabilitation strategies in
      CFS. RESEARCH IMPLICATIONS: This new heuristic framework may inform future
      research aimed at disentangling the complex determination of impaired motor
      performance in CFS, as well as studies aimed at customizing treatment to
      different subtypes of patients.

PMID- 18042609
TI  - Study to establish the usefulness of the one question 'Are you depressed?' in
      screening people with multiple sclerosis for depression.

PMID- 18042612
TI  - Dramatic atherosclerotic vascular burden in a patient with familial lecithin
      cholesterol acyltransferase (LCAT) deficiency.

PMID- 18042613
TI  - Peritoneal thickening is not inevitable in long-term peritoneal dialysis and is
      associated with peritoneal transport characteristics: a two-centre sonographic
      study.
AB  - BACKGROUND: The peritoneum is subject to alterations in the life-long course of
      peritoneal dialysis (PD). Studies of the parietal peritoneum by non-invasive
      ultrasonography in PD patients are limited. We hypothesize that a prolonged PD
      duration is associated with a thicker peritoneum on ultrasonography and
      alterations in Doppler indexes of mesenteric vessels. METHODS: We recruited two
      groups of patients, 18 who had >7 years of PD and 18 who had <12 months of PD. We
      excluded patients with active peritonitis, history of major abdominal surgery,
      cirrhosis or malignancy. We measured the sonographic thickness of the parietal
      peritoneum and Doppler indexes of mesenteric vessels by trans-abdominal
      ultrasonography at two PD units in Taiwan. RESULTS: We found no significant
      difference between two groups of PD patients in peritoneal thickness and in
      Doppler indexes. However, our univariate and multivariate analysis indicated that
      peritoneal thickness is associated with peritoneal transport characteristics
      (dialysate/plasma creatinine) but not with age, duration of dialysis, body
      height, body weight or Doppler index. The peritoneum is significantly thicker in
      rapid transporters than in slow transporters (RUQ: 0.59 +/- 0.40 mm versus 0.27
      +/- 0.29 mm, P = 0.01; LUQ: 0.60 +/- 0.40 mm versus 0.27 +/- 0.32 mm, P = 0.016;
      LQ: 1.07 +/- 0.85 mm versus 0.48 +/- 0.53 mm, P = 0.026). In addition, rapid
      transporters have a marginally lower Doppler resistive index of the superior
      mesenteric artery (0.87 +/- 0.08 versus 0.90 +/- 0.10, P = 0.028). CONCLUSIONS:
      Our data showed that peritoneal thickening is not inevitable in long-term PD
      patients. Sonographic thickness in the parietal peritoneum is associated with
      transport characteristics. Rapid transporters have a significantly thicker
      peritoneum. The Doppler index of mesenteric vessels had no association with PD
      duration or transport characteristics. Trans-abdominal ultrasonography is non
      invasive and useful in evaluating peritoneal characteristics of PD patients.

PMID- 18042614
TI  - Pegylated interferon alfa-2a (40 kD) and ribavirin in haemodialysis patients with
      chronic hepatitis C.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with liver
      dysfunction and hepatocellular carcinoma. In patients with normal kidney
      function, treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV)
      frequently leads to eradication of HCV. Treatment in dialysis patients has long
      been controversial and until recently, the use of RBV was considered to be contra
      indicated. We used plasma trough levels of RBV to promote tolerance, safety and
      efficacy. PEG-IFN alfa-2a (40 kD) was chosen because it is cleared predominantly
      via hepatic metabolism. METHODS: Seven haemodialysis patients with chronic HCV
      infection were eligible and started with 135 microg PEG-IFN alfa-2a (40 kD)
      weekly and 200 mg RBV every other day. Dose adaptations were allowed following
      study guidelines. Genotypes 1 and 4 (five patients) were treated for 48 weeks and
      genotypes 2 and 3 (two patients) for 24 weeks. HCV-RNA was determined after 12,
      24 and 48 weeks (and at 72 weeks for genotypes 1 and 4). RBV trough plasma levels
      were monitored regularly by HPLC-technique. RESULTS: All patients completed the
      treatment. In two patients, the PEG-IFN dose had to be reduced to 90 microg/week
      because of adverse events. To achieve the target range (1.5-2.5 microg/ml) of the
      plasma trough level, the mean RBV dose was increased to a dose between 133 and
      200 mg each day in five patients. Despite an increase of the weekly
      erythropoietin (Epo) dose, two to a max of four red cell transfusions were given
      to four patients. A sustained viral response (SVR) was reached in five patients
      (3/5 with genotype 1/4 and 2/2 with genotype 2/3). CONCLUSION: In our series of
      seven patients, we were able to use RBV monitoring drug levels in combination
      with PEG-IFN alfa-2a (40 kD) and achieve high sustained response rates. However,
      Epo and transfusion requirements may increase. In two patients adverse events
      were observed, but manageable with dose reduction of PEG-IFN.

PMID- 18042615
TI  - Sirolimus ameliorates the enhanced expression of metalloproteinases in a rat
      model of autosomal dominant polycystic kidney disease.
AB  - BACKGROUND: Remodelling of matrix and tubular basement membranes (TBM) is a
      characteristic of polycystic kidney disease. We hypothesized that matrix and TBM
      degradation by metalloproteinases (MMPs) could promote cyst formation. We
      therefore investigated the renal expression of MMPs in the Han:SPRD rat model of
      autosomal dominant polycystic kidney disease (ADPKD) and examined the effect of
      sirolimus treatment on MMPs. METHODS: 5-week-old male heterozygous (Cy/+) and
      wild-type normal (+/+) rats were treated with sirolimus (2 mg/kg/day) through
      drinking water for 3 months. RESULTS: The mRNA and protein levels of MMP-2 and
      MMP-14 were markedly increased in the kidneys of heterozygous Cy/+ animals
      compared to wild-type +/+ as shown by RT-PCR and Western blot analyses for MMP-2
      and MMP-14, and by zymography for MMP-2. Strong MMP-2 expression was detected by
      immunoperoxidase staining in cystic epithelial cells that also displayed an
      altered, thickened TBM. Tissue inhibitor of metalloproteinases-2 (TIMP-2)
      expression was not changed in Cy/+ kidneys. Sirolimus treatment leads to
      decreased protein expression of MMP-2 and MMP-14 in Cy/+, whereas MMP-2 and MMP
      14 mRNA levels and TIMP-2 protein levels were not affected by sirolimus.
      CONCLUSION: In summary, in kidneys of the Han:SPRD rat model of ADPKD, there is a
      marked upregulation of MMP-2 and MMP-14. Sirolimus treatment was associated with
      a marked improvement of MMP-2 and MMP-14 overexpression, and this correlated also
      with less matrix and TBM alterations and milder cystic disease.

PMID- 18042617
TI  - What goes in must come out--the small intestine modulates renal phosphate
      excretion.

PMID- 18042618
TI  - Studying atrial fibrillation: what can we learn from the AFTherapy study?

PMID- 18042619
TI  - Conventional and dedicated atrial overdrive pacing for the prevention of
      paroxysmal atrial fibrillation: the AFTherapy study.
AB  - AIMS: This investigation was conducted to determine the effectiveness of several
      conventional overdrive pacing modalities (single rate and rate responsive pacing
      at various lower rates) and of four dedicated preventive pacing algorithms in the
      suppression of paroxysmal atrial fibrillation (AF). METHOD AND RESULTS: In this
      multi-centre, randomized trial, 372 patients with drug-refractory paroxysmal AF
      were enrolled. Patients received a dual-chamber pacing device capable of
      delivering conventional pacing therapy as well as dedicated AF prevention pacing
      therapies and to record detailed AF-related diagnostics. The primary endpoint was
      AF burden, whereas secondary endpoints were time to first AF episode and averaged
      sinus rhythm duration. During a conventional pacing phase, patients were
      randomized to single rate or rate-responsive pacing with lower rates of either 70
      or 85 min(-1) or to a control group with single rate pacing at 40 min(-1). In the
      subsequent preventive pacing phase, patients underwent pacing at a lower rate of
      70 min(-1) with or without concomitant application of four preventive pacing
      algorithms. A substantial amount of data was excluded from the analysis because
      of atrial-sensing artefacts, identified in the device-captured diagnostics. In
      the conventional pacing phase, no significant differences were found between
      various lower rates and the control group receiving single rate pacing at 40 min(
      1) or between single rate and rate-responsive pacing. Patients receiving
      preventive pacing with all four therapies enabled had a similar AF burden
      compared with patients treated with conventional pacing at 70 min(-1) (P = 0.47).
      CONCLUSIONS: The results do not demonstrate a significant effect of conventional
      atrial overdrive pacing or preventive pacing therapies. However, the observations
      provided important information for further consideration with respect to the
      design and conduct of future studies on the effect of atrial pacing therapies for
      the reduction of AF.

PMID- 18042620
TI  - CLASP localizes in two discrete patterns on cortical microtubules and is required
      for cell morphogenesis and cell division in Arabidopsis.
AB  - In animals and yeast, CLASP proteins are microtubule plus-end tracking proteins
      (+TIPS) involved in the regulation of microtubule plus-end dynamics and
      stabilization. Here we show that mutations in the Arabidopsis CLASP homolog
      result in various plant growth reductions, cell form defects and reduced mitotic
      activity. Analysis of Arabidopsis plants that carry a YFP:AtCLASP fusion
      construct regulated by the AtCLASP native promoter showed similarities to the
      described localization of the animal CLASP proteins, but also prominent
      differences including punctate and preferential localization along cortical
      microtubules. Colocalization studies of YFP:AtCLASP and CFP:EB1b also showed that
      AtCLASP is enriched at the plus ends of microtubules where it localizes behind
      the AtEB1b protein. Moreover, AtCLASP overexpression causes abnormal cortical
      microtubule bundling and array organization. Cortical microtubule arrays have
      evolved to be prominent in plants, and our findings suggest that plant CLASP
      proteins may have adopted specific functions in regulating cortical microtubule
      properties and cell growth.

PMID- 18042621
TI  - Cep68 and Cep215 (Cdk5rap2) are required for centrosome cohesion.
AB  - The centrosome duplicates during the cell cycle but functions as a single
      microtubule-organising centre until shortly before mitosis. This raises the
      question of how centrosome cohesion is maintained throughout interphase. One
      dynamic model proposes that parental centrioles are held together through
      centriole-associated, entangling filaments. Central to this model are C-Nap1, a
      putative centriolar docking protein and rootletin, a fibrous component. Here we
      identify two novel proteins, Cep68 and Cep215, as required for centrosome
      cohesion. Similar to rootletin, Cep68 decorates fibres emanating from the
      proximal ends of centrioles and dissociates from centrosomes during mitosis.
      Furthermore, Cep68 and rootletin depend both on each other and on C-Nap1 for
      centriole association. Unlike rootletin, overexpression of Cep68 does not induce
      extensive fibre formation, but Cep68 is readily recruited to ectopic rootletin
      fibres. These data suggest that Cep68 cooperates with rootletin and C-Nap1 in
      centrosome cohesion. By contrast, Cep215 associates with centrosomes throughout
      the cell cycle and does not appear to interact with Cep68, rootletin or C-Nap1.
      Instead, our data suggest that Cep215 functionally interacts with pericentrin,
      suggesting that both proteins influence centrosome cohesion through an indirect
      mechanism related to cytoskeletal dynamics.

PMID- 18042622
TI  - Cdk5 regulates differentiation of oligodendrocyte precursor cells through the
      direct phosphorylation of paxillin.
AB  - Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs)
      in order to form myelin, which is required for the rapid propagation of action
      potentials in the vertebrate nervous system. In spite of the considerable
      clinical importance of myelination, little is known about the basic molecular
      mechanisms underlying OL differentiation and myelination. Here, we show that
      cyclin-dependent kinase (Cdk) 5 is activated following the induction of
      differentiation, and that the Cdk5 inhibitor roscovitine inhibits OL
      differentiation. The complexity of the OL processes is also diminished after
      knocking down endogenous Cdk5 using RNAi. We also show that the focal adhesion
      protein paxillin is directly phosphorylated at Ser244 by Cdk5. Transfection of a
      paxillin construct harboring a Ser244 to Ala mutation dramatically inhibits its
      morphological effects. Importantly, phosphorylation of paxillin at Ser244 reduces
      its interaction with focal adhesion kinase (FAK). Taken together, these results
      suggest that phosphorylation of paxillin by Cdk5 is a key mechanism in OL
      differentiation and may ultimately regulate myelination.

PMID- 18042623
TI  - Direct interaction of tyrosinase with Tyrp1 to form heterodimeric complexes in
      vivo.
AB  - Mutations of the critical and rate-limiting melanogenic enzyme tyrosinase (Tyr)
      result in hypopigmentation of the hair, skin and eyes. Two other related enzymes,
      Tyrp1 and Dct, catalyze distinct post-Tyr reactions in melanin biosynthesis. Tyr,
      Tyrp1 and Dct have been proposed to interact with and stabilize each other in
      multi-enzyme complexes, and in vitro, Tyr activity is more stable in the presence
      of Tyrp1 and/or Dct. We recently reported that Tyr is degraded more quickly in
      mutant Tyrp1 mouse melanocytes than in wild-type Tyrp1 melanocytes, and that
      decreased stability of Tyr can be partly rescued by infection with wild-type
      Tyrp1. Although interactions between Tyr and Tyrp1 have been demonstrated in
      vitro, there is no direct evidence for Tyr interaction with Tyrp1 in vivo. In
      this study, we use in vivo chemical crosslinking to stabilize the association of
      Tyr with other cellular proteins. Western blot analysis revealed that Tyrp1, but
      not Dct, associates with Tyr in murine melanocytes in vivo, and more
      specifically, in melanosomes. Two-dimensional SDS-PAGE analysis detected
      heterodimeric species of Tyr and Tyrp1. Taken together, these data demonstrate
      that Tyrp1 interacts directly with Tyr in vivo, which may regulate the stability
      and trafficking of melanogenic enzymes and thus pigment synthesis.

PMID- 18042624
TI  - ADF/cofilin family proteins control formation of oriented actin-filament bundles
      in the cell body to trigger fibroblast polarization.
AB  - How formation of the front and rear of a cell are coordinated during cell
      polarization in migrating cells is not well understood. Time-lapse microscopy of
      live primary chick embryo heart fibroblasts expressing GFP-actin show that, prior
      to cell polarization, polymerized actin in the cell body reorganizes to form
      oriented actin-filament bundles spanning the entire cell body. Within an average
      of 5 minutes of oriented actin bundles forming, localized cell-edge retraction
      initiates at either the side or at one end of the newly formed bundles and then
      elaborates around the nearest end of the bundles to form the cell rear, the first
      visual break in cell symmetry. Localized net protrusion occurs at the opposing
      end of the bundles to form the cell front and lags formation of the rear of the
      cell. Consequently, cells acquire full polarity and start to migrate in the
      direction of the long axis of the bundles, as previously documented for already
      migrating cells. When ADF/cofilin family protein activity or actin-filament
      disassembly is specifically blocked during cell polarization, reorganization of
      polymerized actin to form oriented actin-filament bundles in the cell body fails,
      and formation of the cell rear and front is inhibited. We conclude that formation
      of oriented actin-filament bundles in the cell body requires ADF/cofilin family
      proteins, and is an early event needed to coordinate the spatial location of the
      cell rear and front during fibroblast polarization.

PMID- 18042625
TI  - The Ste20-like kinase SvkA of Dictyostelium discoideum is essential for late
      stages of cytokinesis.
AB  - The genome of the social amoeba Dictyostelium discoideum encodes approximately
      285 kinases, which represents approximately 2.6% of the total genome and suggests
      a signaling complexity similar to that of yeasts and humans. The behavior of D.
      discoideum as an amoeba and during development relies heavily on fast
      rearrangements of the actin cytoskeleton. Here, we describe the knockout
      phenotype of the svkA gene encoding severin kinase, a homolog of the human MST3,
      MST4 and YSK1 kinases. SvkA-knockout cells show drastic defects in cytokinesis,
      development and directed slug movement. The defect in cytokinesis is most
      prominent, leading to multinucleated cells sometimes with >30 nuclei. The defect
      arises from the frequent inability of svkA-knockout cells to maintain symmetry
      during formation of the cleavage furrow and to sever the last cytosolic
      connection. We demonstrate that GFP-SvkA is enriched at the centrosome and
      localizes to the midzone during the final stage of cell division. This
      distribution is mediated by the C-terminal half of the kinase, whereas a rescue
      of the phenotypic changes requires the active N-terminal kinase domain as well.
      The data suggest that SvkA is part of a regulatory pathway from the centrosome to
      the midzone, thus regulating the completion of cell division.

PMID- 18042626
TI  - Distinguishing between retention signals and degrons acting in ERAD.
AB  - Endoplasmic reticulum-associated degradation (ERAD) eliminates aberrant proteins
      from the secretory pathway. Such proteins are retained in the endoplasmic
      reticulum and targeted for degradation by the ubiquitin-proteasome system. Cis
      acting motifs can function in ERAD as retention signals, preventing vesicular
      export from the endoplasmic reticulum, or as degrons, targeting proteins for
      degradation. Here, we show that microstp, the C-terminal 20-residue tailpiece of
      the secretory IgM mus heavy chain, functions both as a portable retention signal
      and as an ERAD degron. Retention of microstp fusions of secreted versions of
      thyroid peroxidase and yellow fluorescent protein in the endoplasmic reticulum
      requires the presence of the penultimate cysteine of microstp. In its role as a
      portable degron, the microstp targets the retained proteins for ERAD but does not
      serve as an obligatory ubiquitin-conjugation site. Abolishing microstp
      glycosylation accelerates the degradation of both microstpCys-fused substrates,
      yet absence of the N-glycan eliminates the requirement for the penultimate
      cysteine in the retention and degradation of the unglycosylated yellow
      fluorescent protein. Hence, the dual role played by the microstpCys motif as a
      retention signal and as a degron can be attributed to distinct elements within
      this sequence.

PMID- 18042627
TI  - Neural cell adhesion molecule regulates the cellular response to fibroblast
      growth factor.
AB  - Neural cell adhesion molecule (NCAM) mediates cell-cell adhesion and signaling in
      the nervous system, yet NCAM is also expressed in non-neural tissues, in which
      its function has in most parts remained elusive. We have previously reported that
      NCAM stimulates cell-matrix adhesion and neurite outgrowth by activating
      fibroblast growth factor receptor (FGFR) signaling. Here, we investigated whether
      the interplay between NCAM and FGFR has any impact on the response of FGFR to its
      classical ligands, FGFs. To this end, we employed two fibroblast cell lines, NCAM
      negative L cells and NCAM-positive NIH-3T3 cells, in which the expression of NCAM
      was manipulated by means of transfection or RNAi technologies, respectively. The
      results demonstrate that NCAM expression reduces FGF-stimulated ERK1/2
      activation, cell proliferation and cell-matrix adhesion, in both L and NIH-3T3
      cells. Furthermore, our data show that NCAM inhibits the binding of FGF to its
      high-affinity receptor in a competitive manner, providing the mechanisms for the
      NCAM-mediated suppression of FGF function. In this context, a small peptide that
      mimics the binding of NCAM to FGFR was sufficient to block FGF-dependent cell
      proliferation. These findings point to NCAM as being a major regulator of FGF
      FGFR interaction, thus introducing a novel type of control mechanism for FGFR
      activity and opening new therapeutic perspectives for those diseases
      characterized by aberrant FGFR function.

PMID- 18042628
TI  - Microbiological effects of prior vancomycin use in patients with methicillin
      resistant Staphylococcus aureus bacteraemia.
AB  - BACKGROUND: We sought to determine whether prior vancomycin use (within 30 days)
      in patients who develop methicillin-resistant Staphylococcus aureus (MRSA)
      bacteraemia is associated with isolates of reduced vancomycin susceptibility and
      killing in vitro. METHODS: Thirty-eight MRSA from previously vancomycin-treated
      patients and 43 MRSA from vancomycin-naive patients were evaluated by vancomycin
      and daptomycin CLSI broth microdilution and killing assays. PCR was used to
      determine accessory gene regulator (agr) type and staphylococcal cassette
      chromosome mec (SCCmec) type, and nucleotide sequencing was used to determine spa
      type. RESULTS: Vancomycin MICs were 0.5, 1.0 and 2.0 mg/L for 19, 55 and 7
      isolates, respectively. Daptomycin MICs were 0.25, 0.5, 1.0 and 2.0 mg/L for 4,
      50, 26 and 1 isolate, respectively. The agr-type distribution was agr group II
      (59%), group I (25%) and group III (16%); 90% harboured SCCmec II. The genetic
      background extrapolated by spa-typing showed that 58% of the isolates were of
      clonal complex 5. MRSA bloodstream isolates from patients who had received
      vancomycin within the preceding 30 days had a significantly decreased vancomycin
      killing at 24 h in vitro (median log(10) decrease, 3.1 versus 2.2 cfu/mL; P =
      0.021) and a significantly higher vancomycin MIC than isolates obtained from
      patients without that history (P = 0.002). CONCLUSIONS: MRSA bloodstream isolates
      from patients recently treated with vancomycin may demonstrate reduced
      susceptibility and increased tolerance to vancomycin in vitro. Given that such
      microbiological phenotypes have been associated with reduced vancomycin efficacy,
      consideration may be given to alternative Gram-positive antimicrobial therapy in
      patients who have recently been treated with vancomycin.

PMID- 18042629
TI  - Serine proteases and serine protease inhibitors in testicular physiology: the
      plasminogen activation system.
AB  - The testis is an organ in which a series of radical remodeling events occurs
      during development and in adult life. These events likely rely on a sophisticated
      network of proteases and complementary inhibitors, including the plasminogen
      activation system. This review summarizes our current knowledge on the testicular
      occurrence and expression pattern of members of the plasminogen activation
      system. The various predicted functions for these molecules in the establishment
      and maintenance of the testicular architecture and in the process of
      spermatogenesis are presented.

PMID- 18042630
TI  - Spindle assembly in the absence of chromosomes in mouse oocytes.
AB  - This study was carried out to investigate the contributions of chromosomes to
      spindle assembly in mouse oocytes. We generated two groups of cytoplasts (holo-
      and hemi-cytoplasts) by enucleation of germinal vesicle (GV), metaphase I (MI),
      and metaphase II (MII) oocytes using micromanipulation technology. After in vitro
      culture for 18 h, spindles with different shapes (bi-, mono-, or multipolar)
      formed in most of these cytoplasts except in hemi-GV cytoplasts. Two or more
      spindles were observed in most of holo-GV, holo-MI, and holo-MII cytoplasts
      (76.1, 77.0, and 83.7% respectively). However, the proportions of hemi-MI and
      hemi-MII cytoplasts with multiple sets of spindles decreased to 17.6 and 20.7%
      respectively. A single bipolar spindle was observed in each sham-operated oocyte
      generated by removing different volumes of cytoplasm from the oocytes and keeping
      nuclei intact. Localization of gamma-tubulin showed that microtubule organizing
      centers (MTOCs) were dispersed at each pole of the multiple sets of spindles
      formed in holo-cytoplasts. However, most of the MTOCs aggregated at the two poles
      of the bipolar spindle in sham-operated oocytes. Our results demonstrate that
      chromosomes are not essential for initiating spindle assembly but for directing
      distinct MTOCs to aggregate to form a bipolar spindle. Some factors of
      undetermined nature may pre-exist in an inactive form in GV-stage ooplasm,
      serving as initiators of spindle assembly upon their activation. Moreover, GV
      materials released into the cytoplasm may facilitate spindle assembly in normal
      meiotic maturation.

PMID- 18042631
TI  - Rapid sperm acrosome reaction in the absence of acrosomal CD46 expression in
      promiscuous field mice (Apodemus).
AB  - There is pronounced promiscuity and sperm competition in long-tailed field mice
      (Apodemus sylvaticus). These mice have evolved unusual sperm behaviour favouring
      rapid fertilisation, including dynamic formation of sperm trains and their
      subsequent dissociation. The cell surface complement regulatory (CReg) protein
      CD46 is broadly expressed in eutherian mammals other than rodents, in which it is
      expressed solely on the spermatozoal acrosomal membrane. Ablation of the CD46
      gene has been associated with a faster acrosome reaction (AR) rate in inbred
      laboratory mice. Here, we demonstrate that wild-caught field mice of three
      species, A. sylvaticus, A. flavicollis and A. microps, exhibit a more rapid AR
      than wild-caught house mice Mus musculus or inbred laboratory BALB/c mice. We
      also demonstrate that wild-caught field mice of these three species, unlike house
      mice, produce alternatively spliced transcripts of testicular CD46 mRNA lacking
      exons 5-7 or 6-7, together with an extended 3' - and often truncated 5'-utr,
      leading to failure to express any sperm CD46 protein in both the testis and
      epididymis. Male field mice may therefore have traded expression of this CReg
      protein for acrosomal instability, providing a novel genus-specific strategy to
      favour rapid fertilisation and competitive advantage in the promiscuous
      reproductive behaviour of wild field mice.

PMID- 18042632
TI  - Germ cell-less like-2 protein is a new component of outer dense fibers in rat
      sperm flagella.
AB  - We have analyzed the expression profiles of ten genes in terms of testis
      development and organ specificity in rat, which were selected from 215 round
      spermatid-specific transcripts listed in a database. Out of the ten genes, we
      directed our attention to one gene, a germ cell-less like-2 gene (gcl-2), a
      homolog of Drosophila gcl gene (gcl), which is a component of the germ plasma and
      required for primordial germ cell formation. Rat genome contains duplicate rat
      gcl-2 (rgcl-2) genes, rgcl-2A and rgcl-2B, both of which are located at Xq13. RT
      PCR analysis showed that the expression of the two genes was up-regulated during
      testis development and that they were predominantly expressed in the testis. Both
      rgcl-2A and rgcl-2B encode a protein of 498 amino acid residues, showing 90.56%
      identity at the amino acid level. Confocal laser scanning microscopy revealed
      that rgcl-2 protein was synthesized in the cytoplasm of elongating spermatids and
      at least a part of it was integrated into the middle piece of spermatozoa during
      spermiogenesis. Immunogold electron microscopy uncovered that rgcl-2 was
      localized at the abaxial (convex) surface of outer dense fibers (ODF) of rat
      sperm flagella. Therefore, we concluded that rgcl-2 is a new component of ODF in
      sperm flagella.

PMID- 18042633
TI  - Stem cell factor affects fate determination of human gonocytes in vitro.
AB  - The stem cell factor (SCF), binding its tyrosine kinase receptor c-Kit, has been
      shown to play essential roles in the proliferation, differentiation, and survival
      of germline cells. However, few reports are available about the effect of SCF on
      the development of human gonocytes within the fetal testis. The objective of this
      study was to investigate whether SCF affects the biological behaviors of human
      gonocytes before or after they enter the mitotic arrest stage. Employing an organ
      culture system, we observed that addition of exogenous SCF could influence the
      morphology of human gonocytes in vitro. Moreover, SCF was able to trigger the
      colony formation of round gonocytes, which were characterized positive for
      alkaline phosphatase activity, Oct-4, SSEA-4, and c-Kit as well. We found that
      SCF exerted actions in a dose- and age-dependent manner, although the stimulatory
      effect lasted no more than 14 days. We also showed that SCF played a role in
      suppressing the apoptosis of human gonocytes. Blocking of SCF signaling with
      either phosphatidylinositol 3-kinase or mitogen-activated protein kinase
      inhibitor resulted in similar apoptotic features as well as the SCF-withdrawal
      cultures. Taken together, we report that SCF acts as a potent regulator in the
      fate determination of human gonocytes. Our studies should form the basis for in
      vitro studies and facilitate investigation of the molecular mechanisms underlying
      this unique stage.

PMID- 18042634
TI  - Decontamination of leukemic cells and enrichment of germ cells from testicular
      samples from rats with Roser's T-cell leukemia by flow cytometric sorting.
AB  - Testicular germ cell transplantation is a novel strategy for preservation of
      fertility in prepubertal cancer patients, but the risk of reseeding tumor cells
      into cured patients presently limits clinical application of this approach. To
      date, no systematic evaluation of the limitations of surface marker-based
      decontamination of testicular samples with acute lymphoblastic leukemia has been
      performed. Here, surface markers for leukemic (CD4 and major histocompatibility
      complex class I) and germ cells (epithelia cell adhesion molecule) in testicular
      samples infiltrated with Roser's T-cell leukemia were identified. These markers
      were then used to delete leukemic cells and/or select for germ cells by flow
      cytometry (FACS). The resulting cell populations were analyzed by FACS,
      immunocytochemistry, or evaluation of leukemia transmission in syngeneic piebald
      variegated rats. Simple positive selection of germ cells or deletion of leukemic
      cells using specific surface markers was unable to effectively decontaminate
      testicular samples. The poor specificity of spermatogonial surface markers and
      aggregation of germ and leukemic cells limited the positive selection of germ
      cells, while immunophenotypic variation among lymphoblastic leukemia cells
      prevented adequate deletion of leukemic cells. Enzymatic treatment to disperse
      the testicular cells and feature of the intratesticular environment contributed
      to this immunophenotypic variation. Only germ cell selection in combination with
      leukemic cell deletion prevented leukemia transmission in association with
      intratesticular injection of the sorted cells. However, with such combined
      sorting, only 0.23% of the original testicular cells were recovered. With
      presently available techniques, flow cytometric purification of germ cells from a
      leukemic donor is not sufficiently effective or safe for clinical use.

PMID- 18042635
TI  - Epigenetic alteration of the donor cells does not recapitulate the reprogramming
      of DNA methylation in cloned embryos.
AB  - Epigenetic reprogramming is a prerequisite process during mammalian development
      that is aberrant in cloned embryos. However, mechanisms that evolve abnormal
      epigenetic reprogramming during preimplantation development are unclear. To trace
      the molecular event of an epigenetic mark such as DNA methylation, bovine
      fibroblasts were epigeneticallyaltered by treatment with trichostatin A (TSA) and
      then individually transferred into enucleated bovine oocytes. In the TSA-treated
      cells, expression levels of histone deacetylases and DNA methyltransferases were
      reduced, but the expression level of histone acetyltransferases such as Tip60 and
      histone acetyltransferase 1 (HAT1) did not change compared with normal cells. DNA
      methylation levels of non-treated (normal) and TSA-treated cells were 64.0 and
      48.9% in the satellite I sequence (P < 0.05) respectively, and 71.6 and 61.9% in
      the alpha-satellite sequence respectively. DNA methylation levels of nuclear
      transfer (NT) and TSA-NT blastocysts in the satellite I sequence were 67.2 and
      42.2% (P < 0.05) respectively, which was approximately similar to those of normal
      and TSA-treated cells. In the alpha-satellite sequence, NT and TSA-NT embryos
      were substantially demethylated at the blastocyst stage as IVF-derived embryos
      were demethylated. The in vitro developmental rate (46.6%) of TSA-NT embryos that
      were individually transferred with TSA-treated cells was higher than that (31.7%)
      of NT embryos with non-treated cells (P < 0.05). Our findings suggest that the
      chromatin of a donor cell is unyielding to the reprogramming of DNA methylation
      during preimplantation development, and that alteration of the epigenetic state
      of donor cells may improve in vitro developmental competence of cloned embryos.

PMID- 18042636
TI  - The block to apoptosis in bovine two-cell embryos involves inhibition of caspase
      9 activation and caspase-mediated DNA damage.
AB  - The capacity of the preimplantation embryo to undergo apoptosis in response to
      external stimuli is developmentally regulated. Acquisition of apoptosis does not
      occur in the cow embryo until between the 8- and 16-cell stages. The purpose of
      the present experiments was to determine the mechanism by which apoptosis is
      blocked in the bovine two-cell embryo. Heat shock (41 degrees C for 15 h) did not
      increase activity of caspase-9 or group II caspases (caspase-2, -3, and -7) in
      two-cell embryos but did in day 5 embryos. Exposure of embryos to carbonyl
      cyanide 3-chlorophenylhydrazone (CCCP) to depolarize mitochondria resulted in
      activation of caspase-9 and group II caspases at both stages of development. For
      day 5 embryos, CCCP also increased the proportion of blastomeres that underwent
      DNA fragmentation as determined by the TUNEL assay. In contrast, CCCP did not
      increase TUNEL labeling when applied at the two-cell stage. In conclusion,
      failure of heat shock to increase caspase-9 and group II caspase activity in the
      two-cell embryo indicates that the signaling pathway leading to mitochondrial
      depolarization and caspase activation is inhibited at this stage of development.
      The fact that CCCP treatment of two-cell embryos induced caspase-9 and group II
      caspase activity indicates that caspase activation is possible following
      mitochondrial depolarization. However, since CCCP did not increase TUNEL labeling
      of two-cell embryos, actions of group II-caspases to activate DNases is
      inhibited.

PMID- 18042637
TI  - Evaluation of triploid<-->diploid and trisomy-3<-->diploid mouse chimeras as
      models for investigating how lineage restriction occurs in confined placental
      mosaicism.
AB  - Human confined placental mosaicism (CPM), where the placental trophoblast is
      mosaic for a chromosome abnormality but the fetus is chromosomally normal, can
      cause problems for prenatal diagnosis, but its causes are poorly understood.
      Tetraploid<-->diploid chimeras provide a model for the development of one type of
      CPM, but animal models for other types of restricted mosaicism are needed. The
      objective of the present study was to evaluate triploid<-->diploid and trisomy-3<
      ->diploid chimeric mouse conceptuses as new models for investigating the
      development of restricted mosaicism. Novel stocks of mice were generated to
      produce triploid and trisomy-3 embryos that could be identified by DNA in situ
      hybridisation to a chromosome 3 transgenic marker. Triploid<-->diploid and
      trisomy-3<-->diploid mouse chimeras were produced by embryo aggregation, and the
      contribution of triploid or trisomy-3 cells was analysed in the fetus and
      extraembryonic tissues. Only two trisomy-3<-->diploid chimeras were analysed but
      trisomy-3 cells contributed well to all lineages, so these chimeras did not show
      restricted mosaicism. In contrast, triploid cells usually contributed poorly to
      all lineages in the ten 3n<-->2n chimeras analysed. They contributed more to the
      primitive endoderm derivatives than other lineages and were present in the
      primitive endoderm derivatives of all ten chimeras, but excluded from fetuses and
      trophectoderm derivatives in some cases. This pattern of restricted mosaicism
      differs from that reported for tetraploid cells in tetraploid<-->diploid
      chimeras, and triploid<-->diploid chimeras may provide a useful model for the
      development of some types of restricted mosaicism in human conceptuses.

PMID- 18042638
TI  - Identification of interleukin-1beta regulated genes in uterine smooth muscle
      cells.
AB  - We analyzed the response of uterine smooth muscle cells to interleukin-1beta (IL
      1beta). We first showed that PHM1-31 myometrial cells, our cellular model, are
      contractile. To determine the molecular mechanisms of uterine smooth muscle cell
      activation by proinflammatory cytokines, we performed genechip expression array
      profiling studies of PHM1-31 cells in the absence and the presence of IL-1beta.
      In total, we identified 198 known genes whose mRNA levels are significantly
      modulated (> 2.0-fold change) following IL-1beta exposure. We confirmed the
      expression changes for selected genes by independent mRNA and protein analysis.
      The group of genes induced by IL-1beta includes transcription factors and
      inflammatory response genes such as nuclear factor of kappa light polypeptide
      gene enhancer in B-cells (NFkappaB), pentraxin-related gene (PTX3), and tumor
      necrosis factor alpha-induced protein 3/A20 (TNFAIP3/A20). We also found up
      regulation of chemokines like C-X-C motif ligand 3 (CXCL3) and extracellular
      matrix remodeling signaling molecules like tenascin C (TNC). Our data suggest
      that IL-1beta elicits the rapid activation of a cellular network of genes
      particularly implicated in inflammatory response that may create a cellular
      environment favorable for myometrial cell contraction. Our results provide novel
      insights into the mechanisms of uterine smooth muscle cell regulation and
      possibly infection-induced preterm labor.

PMID- 18042639
TI  - Ontogeny and nutritional programming of mitochondrial proteins in the ovine
      kidney, liver and lung.
AB  - This study investigated the developmental and nutritional programming of two
      important mitochondrial proteins, namely voltage-dependent anion channel (VDAC)
      and cytochrome c, in the sheep kidney, liver and lung. The effect of maternal
      nutrient restriction between early and mid-gestation (i.e. 28- to 80-day
      gestation, the period of maximal placental growth) on the abundance of these
      proteins was also examined in fetal and juvenile offspring. Fetuses were sampled
      at 80 and 140 days of gestation (term approximately 147 days), and postnatal
      animals at 1 and 30 days and 6 months of age. The abundance of VDAC peaked at 140
      days of gestation in the lung, compared with 1 day after birth in the kidney and
      liver, whereas cytochrome c abundance was greatest at 140 days of gestation in
      the liver, 1 day after birth in the kidney and 6 months of age in lungs. This
      differential ontogeny in mitochondrial protein abundance between tissues was
      accompanied with very different tissue-specific responses to changes in maternal
      food intake. In the liver, maternal nutrient restriction only increased
      mitochondrial protein abundance at 80 days of gestation, compared with no effect
      in the kidney. In contrast, in the lung mitochondrial protein, abundance was
      raised near to term, whereas VDAC abundance was decreased by 6 months of age.
      These findings demonstrate the tissue-specific nature of mitochondrial protein
      development that reflects differences in functional adaptation after birth. The
      divergence in mitochondrial response between tissues to maternal nutrient
      restriction early in pregnancy further reflects these differential ontogenies.

PMID- 18042640
TI  - Treatment with an inhibitor of catechol-O-methyltransferase activity reduces
      preterm birth and impedes cervical resistance to stretch in pregnant rats.
AB  - Catechol-O-methyltransferase (COMT) enzyme catalyzes the methylation of the 2- or
      4-hydroxyestrogens to 2- or 4-methoxyestrogens. Both the hydroxyestrogens and
      methoxyestrogens have been shown to block or enhance the effects of estrogen
      respectively. Our objective was to investigate the potential role of COMT in
      parturition and cervical ripening using a rat model. Immunohistochemistry was
      conducted to detect and localize the COMT protein in rat uterine tissues during
      pregnancy. We measured the longitudinal changes in urinary 2-hydroxyestrogen
      before, during, and after pregnancy in rats. Animal studies were conducted to
      determine the effect of treatment with a selective COMT inhibitor on (1)
      mifepristone-induced preterm birth and (2) cervical resistance to stretch in
      pregnant rats. The intensity of staining for the COMT protein differed within the
      luminal epithelium, uterine gland epithelium, endometrium, and myometrium during
      pregnancy. Levels of staining for the COMT protein in rat myometrium were highest
      on day 1 and lowest on days 8 and 13, but high levels returned by days 16 and 19
      of pregnancy. The levels of urinary 2-hydroxyestrogen gradually increased in the
      first 2 weeks of pregnancy, peaked from days 16 to 18 of pregnancy, and then
      gradually returned to pre-pregnancy levels after delivery. The percentage of pups
      retained in the uterus of pregnant rats treated with both mifepristone and COMT
      inhibitor (48 +/- 15%) was significantly higher (P < 0.05) when compared with the
      value of pregnant rats treated with mifepristone alone (12 +/- 4%). The
      resistance to stretch was significantly higher (P < 0.05) in cervical tissues
      from the pregnant rats treated with COMT inhibitor (0.28) when compared with
      cervical tissues taken from rats treated with vehicle control (0.18). Modulation
      of COMT activity may play a role in the regulation of myometrial contractility
      and cervical ripening during pregnancy.

PMID- 18042641
TI  - Early and long-lasting protection from arthritis in tumour necrosis factor alpha
      (TNFalpha) transgenic mice vaccinated against TNFalpha.
AB  - OBJECTIVE: To evaluate the effect in mice with arthritis of active anti-tumour
      necrosis factor (TNF)alpha immunotherapy based on a keyhole limpet haemocyanin
      human TNFalpha heterocomplex (hTNFalpha kinoid or TNFK) adjuvanted in incomplete
      Freund adjuvant. Immunotherapy was evaluated also with methotrexate. METHODS:
      Human TNFalpha-transgenic mice received TNFK with or without methotrexate. Follow
      up ranged from 6 weeks (short term) to 17 weeks (long term). Arthritis was
      evaluated clinically and histologically. Monitoring included titration of anti
      hTNFalpha antibodies by ELISA and neutralisation assay. RESULTS: Vaccination with
      TNFK was associated with rapid-onset, long-lasting protection. Long-term results
      showed significantly milder arthritis in vaccinated animals than in control
      animals at the peak of the disease. Vaccination was followed by resolution of the
      clinical evidence of arthritis, contrasting with severe progressive arthritis in
      the control group. Histological improvements with decreased inflammation and
      destruction were noted in all immunised groups, even after the shortest follow-up
      (6 weeks). High titres of neutralising anti-hTNFalpha antibodies were detected as
      early as the fifth week post immunisation and persisted over time. Methotrexate
      given concomitantly with the vaccine did not influence either the effect on
      arthritis or the anti-hTNFalpha antibody titres. CONCLUSION: Anti-cytokine
      induction of autoimmune protection against chronic hTNFalpha overproduction is an
      efficient alternative to TNFalpha blockade in experimental arthritis and can be
      achieved using a TNFK vaccine.

PMID- 18042642
TI  - Responsiveness to anti-tumour necrosis factor alpha therapy is related to pre
      treatment tissue inflammation levels in rheumatoid arthritis patients.
AB  - OBJECTIVE: The response of rheumatoid arthritis (RA) patients to treatment with
      neutralising antibodies to tumour necrosis factor alpha (TNFalpha) is highly
      variable. The underlying mechanism for therapy responsiveness is currently
      unknown. We therefore evaluated the relationship between baseline molecular
      profiles of synovial tissues from RA patients and the clinical response to
      treatment with infliximab. METHODS: Synovial biopsies were obtained by
      arthroscopy from 18 RA patients with active disease (28 joint count Disease
      Activity Score (DAS28) > or = 3.2) before initiation of treatment with
      infliximab. All patients were on stable methotrexate treatment. Clinical response
      at 16 weeks was defined as a reduction in DAS28 of > or = 1.2, non-response as
      reduction in DAS28 < 1.2. Large-scale gene expression profiling using microarrays
      was performed on synovial tissue samples. To identify biological processes in
      synovial biopsies that could discriminate between responders and non-responders,
      we performed pathway analysis on the expression profiles. RESULTS: A total of 12
      patients responded to therapy, while 6 patients failed to fulfil the response
      criteria. We identified several biological processes, related to inflammation,
      which were up-regulated in patients who responded to therapy, compared to those
      who did not show clinical improvement. CONCLUSION: These results indicate that
      patients with a high level of tissue inflammation are more likely to benefit from
      anti-TNFalpha treatment.

PMID- 18042643
TI  - Flexible, capacity-limited activity of posterior parietal cortex in perceptual as
      well as visual short-term memory tasks.
AB  - It has recently been shown, using functional magnetic resonance imaging with a
      change detection paradigm, that activity in posterior parietal cortex (PPC)
      correlates with the limited number of objects held in visual short-term memory
      (VSTM). We replicate this finding and extend it to tasks that use similar
      stimuli, but without explicit memory requirements. As well as a perceptual task
      used previously (detecting an item at fixation), 2 additional tasks were designed
      to increase attentional demands across space (searching for a red item anywhere
      in the array) and across both space and time (detecting a staggered offset after
      prolonged viewing of the array). During the VSTM task, a capacity-limited set
      size effect was seen in PPC as well as occipital and frontal regions. However,
      the PPC showed similar activity during 2 of the tasks not requiring VSTM. These
      findings cannot easily be explained by behavioral performance measures or memory
      demands alone, suggesting a role of the PPC in processing a limited number of
      discrete object representations, whether in the current perceptual scene or
      working memory. The differential influence of item load across perceptual tasks
      is consistent with task requirements affecting the form of these representations.

PMID- 18042644
TI  - Identification of novel modulators of mitochondrial function by a genome-wide
      RNAi screen in Drosophila melanogaster.
AB  - Mitochondrial dysfunction is associated with many human diseases. There has not
      been a systematic genetic approach for identifying regulators of basal
      mitochondrial biogenesis and function in higher eukaryotes. We performed a genome
      wide RNA interference (RNAi) screen in Drosophila cells using mitochondrial
      Citrate synthase (CS) activity as the primary readout. We screened 13,071 dsRNAs
      and identified 152 genes that modulate CS activity. These modulators are involved
      in a wide range of biological processes and pathways including mitochondrial
      related functions, transcriptional and translational regulation, and signaling
      pathways. Selected hits among the 152 genes were further analyzed for their
      effect on mitochondrial CS activity in transgenic flies or fly mutants. We
      confirmed a number of gene hits including HDAC6, Rpd3(HDAC1), CG3249, vimar,
      Src42A, klumpfuss, barren, and smt3 which exert effects on mitochondrial CS
      activities in vivo, demonstrating the value of Drosophila genome-wide RNAi
      screens for identifying genes and pathways that modulate mitochondrial function.

PMID- 18042646
TI  - Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a
      novel cause of congenital hypothyroidism.
AB  - CONTEXT: Dual oxidase 2 (DUOX2) is the catalytic core of the H(2)O(2) generator
      crucial for the iodination of thyroglobulin in thyroid hormone synthesis. DUOX2
      deficiency produces congenital hypothyroidism (CH) in humans and mice. We
      recently cloned a novel gene, the product of which (dual oxidase maturation
      factor 2; DUOXA2) is required to express DUOX2 enzymatic activity. OBJECTIVE: Our
      objective was to identify DUOXA2 mutations as a novel cause of CH due to
      dyshormonogenesis. PATIENTS: Subjects included 11 CH patients with partial iodine
      organification defect but negative for other known genetic causes of partial
      iodine organification defect. RESULTS: One Chinese patient born to
      nonconsanguineous parents was homozygous for a nonsense mutation (p.Y246X),
      producing a truncated DUOXA2 protein lacking transmembrane helix 5 and the C
      terminal cytoplasmic domain. The mutant protein was inactive in reconstituting
      DUOX2 in vitro. Pedigree analysis demonstrated recessive inheritance, because
      heterozygous carriers had normal thyroid function including negative results in
      neonatal TSH screening. One heterozygous carrier of Y246X was identified in
      unrelated Chinese controls (n = 92) but not in Caucasian or Japanese controls,
      indicating that homozygosity for Y246X could be a frequent cause of CH in
      Chinese. Functional studies suggest that the DUOXA2 paralog (DUOXA1) can
      partially compensate DUOXA2 deficiency, consistent with the proband having a
      milder CH phenotype than patients with biallelic DUOX2 nonsense mutations.
      CONCLUSIONS: We report the first mutation in DUOXA2, identified in a patient with
      CH and dyshormonogenic goiter. Results of our studies provide evidence for the
      critical role of DUOXA2 in thyroid hormonogenesis. Biallelic DUOXA2 mutations are
      a novel genetic event in permanent CH.

PMID- 18042645
TI  - Genome-wide mapping and analysis of active promoters in mouse embryonic stem
      cells and adult organs.
AB  - By integrating genome-wide maps of RNA polymerase II (Polr2a) binding with gene
      expression data and H3ac and H3K4me3 profiles, we characterized promoters with
      enriched activity in mouse embryonic stem cells (mES) as well as adult brain,
      heart, kidney, and liver. We identified approximately 24,000 promoters across
      these samples, including 16,976 annotated mRNA 5' ends and 5153 additional sites
      validating cap-analysis of gene expression (CAGE) 5' end data. We showed that
      promoters with CpG islands are typically non-tissue specific, with the majority
      associated with Polr2a and the active chromatin modifications in nearly all the
      tissues examined. By contrast, the promoters without CpG islands are generally
      associated with Polr2a and the active chromatin marks in a tissue-dependent way.
      We defined 4396 tissue-specific promoters by adapting a quantitative index of
      tissue-specificity based on Polr2a occupancy. While there is a general
      correspondence between Polr2a occupancy and active chromatin modifications at the
      tissue-specific promoters, a subset of them appear to be persistently marked by
      active chromatin modifications in the absence of detectable Polr2a binding,
      highlighting the complexity of the functional relationship between chromatin
      modification and gene expression. Our results provide a resource for exploring
      promoter Polr2a binding and epigenetic states across pluripotent and
      differentiated cell types in mammals.

PMID- 18042647
TI  - Association of a nicotinic receptor mutation with reduced height and blunted
      physostigmine-stimulated growth hormone release.
AB  - BACKGROUND: Pulsatile GH secretion from the anterior pituitary is a key mediator
      of human growth regulation and is affected by a number of genetic and
      environmental factors. Activation of neuronal nicotinic acetylcholine (nACh)
      receptors promotes GH release, but the role of these receptors in growth
      regulation is unknown. AIM: Our aim was to assess the effect of a mutation in the
      alpha4 subunit of the nACh receptor on cholinergic-mediated GH release. METHODS:
      Forty-one healthy volunteers (24 male, age 36.2 +/- 12.2 yr, mean +/- sd) and 13
      subjects with the alpha4-Ser248Phe mutation (four male, age 43.2 +/- 16.8 yr)
      were studied. Serum levels of GH, LH, FSH, prolactin, TSH, free T(4), and
      cortisol were measured at baseline and at regular intervals after infusion of
      physostigmine. Height and weight were recorded in all participants as well as
      from additional family members with (n = 11, four male) and without (n = 16,
      seven male) the mutation. RESULTS: Subjects with the mutation were shorter (1.62
      +/- 0.08 vs. 1.72 +/- 0.09 m, P < 0.05) and had a greater body mass index (31 +/-
      6 vs. 24 +/- 3 kg/m(2), P < 0.05) than healthy volunteers and unaffected members
      of the pedigree. In controls, physostigmine markedly increased the serum levels
      of GH (mean increase, +732%). In contrast, the response to physostigmine was
      markedly blunted in subjects with the mutation (+104%, P > 0.2 vs. control).
      CONCLUSIONS: These findings suggest a role of the nACh receptor in human growth
      regulation.

PMID- 18042648
TI  - L-thyroxine requirement in patients with autoimmune hypothyroidism and parietal
      cell antibodies.
AB  - BACKGROUND: Hypothyroid patients on l-T(4) therapy may require replacement doses
      exceeding the theoretical needs to normalize serum TSH due to low patient
      compliance, drugs interference, and malabsorption. OBJECTIVE: We examined whether
      autoimmune gastritis might cause increased l-T(4) requirement in patients with
      autoimmune thyroiditis receiving l-T(4) replacement. PATIENTS: We studied 391
      patients with clinical or subclinical hypothyroidism from autoimmune thyroiditis
      who had achieved normal serum TSH concentration (0.3-3.0 microU/ml) under l-T(4)
      for at least 6 months. Patients were screened for serum parietal cell antibodies
      (PCA) as a marker of autoimmune gastritis, and the PCA status was correlated with
      the l-T(4) dose. We also studied a group of 60 patients receiving l-T(4)
      replacement after total thyroidectomy. RESULTS: PCA-positive (155 of 391) and PCA
      negative (236 of 391) patients did not differ for pretherapy serum TSH levels and
      thyroid volume. The l-T(4) requirement was significantly (P = 0.002) higher in
      PCA-positive (1.24 +/- 0.40 microg/kg x d) than in PCA-negative patients (1.06 +/
      0.36 microg/kg x d), and a significant positive correlation was found between l
      T(4) requirement and serum PCA levels. Among PCA-positive patients, l-T(4)
      requirement was even higher in those with proven gastritis (1.52 +/- 0.40
      microg/kg x d) compared with those without gastric damage (1.15 +/- 0.33
      microg/kg x d) (P < 0.0001). The increased l-T(4) requirement was confirmed also
      in PCA-positive thyroidectomized patients (1.81 +/- 0.27 microg/kg x d) compared
      with PCA-negative thyroidectomized patients (1.52 +/- 0.24 microg/kg x d).
      Independent variables affecting l-T(4) requirement were PCA and serum TSH at
      diagnosis. CONCLUSIONS: Autoimmune gastritis is an additional factor affecting l
      T(4) requirement in patients with autoimmune thyroiditis. Serum PCA measurement
      should be considered in patients with an unexplained high requirement of l-T(4).

PMID- 18042649
TI  - Fat mass accumulation during childhood determines insulin sensitivity in early
      adulthood.
AB  - BACKGROUND/OBJECTIVES: Low birth weight and postnatal catch-up growth have been
      associated with an increased risk for diabetes mellitus type II (DMII). We
      evaluated the contribution of birth and adult size, body composition, and waist
      to-hip ratio to DMII risk factors in young adulthood. METHODS: In a group of 136
      young adults, aged 18-24 yr, insulin sensitivity and disposition index were
      determined by frequent sampling iv glucose tolerance test. The association of
      clinical parameters with these variables was analyzed with multiple regression
      modeling. In addition, differences in insulin sensitivity and disposition index,
      a measure for beta-cell function, were analyzed in four subgroups, young adults
      either born small for gestational age SGA with short stature (n = 25) or SGA with
      catch-up growth (n = 23) or born appropriate for gestational age with idiopathic
      short stature (n = 23) or with normal stature (controls) (n = 26). RESULTS: Fat
      mass was the only significant predictor of insulin sensitivity, whereas birth
      length and birth weight were not significant. After correction for age, gender,
      and adult body size, insulin sensitivity was significantly lower in subjects born
      SGA with catch-up growth compared with controls. None of the variables had a
      significant influence on disposition index, and there was no significant
      difference in disposition index between the subgroups. CONCLUSIONS: Our data show
      that a higher body fat mass at 21 yr is associated with reduced insulin
      sensitivity, independent of birth size. These findings have important
      implications for public health practice.

PMID- 18042650
TI  - Measurements of islet function and glucose metabolism with the dipeptidyl
      peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes.
AB  - OBJECTIVE: Pharmacological inhibition with the dipeptidyl peptidase 4 (DPP-4)
      inhibitor vildagliptin prolongs the action of endogenously secreted incretin
      hormones leading to improved glycemic control in patients with type 2 diabetes
      mellitus (T2DM). We undertook a double-blinded, randomized-order, crossover study
      to examine the vildagliptin mechanisms of action on islet function and glucose
      utilization. RESEARCH DESIGN AND METHODS: Participants with T2DM (n = 16) who had
      a baseline hemoglobin A(1c) of 7.1 +/- 0.2% completed a crossover study with 6 wk
      of treatment with vildagliptin and 6 wk with placebo. At the completion of each
      arm, participants had a study of postprandial metabolism and a two-step glucose
      clamp performed at 20 and 80 mU/min x m(2) insulin infusions. RESULTS:
      Vildagliptin increased postprandial glucagon-like peptide-1 and glucose-dependent
      insulinotropic polypeptide by 3- and 2-fold, respectively, reduced fasting plasma
      glucose and postprandial plasma glucose by 1.3 +/- 0.3 mmol/liter and 1.6 +/- 0.3
      mmol/liter (both P <0.01), and improved glucose responsiveness of insulin
      secretion by 50% (P < 0.01). Vildagliptin lowered postprandial glucagon by 16% (P
      <0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance
      improved after vildagliptin (P < 0.01). CONCLUSIONS: Vildagliptin improves islet
      function in T2DM and improves glucose metabolism in peripheral tissues.

PMID- 18042651
TI  - Acute effects of ghrelin administration on glucose and lipid metabolism.
AB  - CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids,
      but it is uncertain whether this is secondary to the concomitant release of GH.
      OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate
      metabolism. DESIGN: This was a randomized, single-blind, placebo-controlled two
      period crossover study. SETTING: The study was performed in a university clinical
      research laboratory. PARTICIPANTS: Eight healthy men aged 27.2 +/- 0.9 yr with a
      body mass index of 23.4 +/- 0.5 kg/m(2) were included in the study. INTERVENTION:
      Subjects received infusion of ghrelin (5 pmol x kg(-1) x min(-1)) or placebo for
      5 h together with a pancreatic clamp (somatostatin 330 microg x h(-1), insulin
      0.1 mU x kg(-1) x min(-1), GH 2 ng x kg(-1) x min(-1), and glucagon 0.5 ng.kg(-1)
      x min(-1)). A hyperinsulinemic (0.6 mU x kg(-1) x min(-1)) euglycemic clamp was
      performed during the final 2 h of each infusion. RESULTS: Basal and insulin
      stimulated glucose disposal decreased with ghrelin [basal: 1.9 +/- 0.1 (ghrelin)
      vs. 2.3 +/- 0.1 mg x kg(-1) x min(-1), P = 0.03; clamp: 3.9 +/- 0.6 (ghrelin) vs.
      6.1 +/- 0.5 mg x kg(-1) x min(-1), P = 0.02], whereas endogenous glucose
      production was similar. Glucose infusion rate during the clamp was reduced by
      ghrelin [4.0 +/- 0.7 (ghrelin) vs. 6.9 +/- 0.9 mg.kg(-1) x min(-1); P = 0.007],
      whereas nonesterified fatty acid flux increased [131 +/- 26 (ghrelin) vs. 69 +/-
      5 micromol/min; P = 0.048] in the basal period. Regional lipolysis (skeletal
      muscle, sc fat) increased insignificantly with ghrelin infusion. Energy
      expenditure during the clamp decreased after ghrelin infusion [1539 +/- 28
      (ghrelin) vs. 1608 +/- 32 kcal/24 h; P = 0.048], but the respiratory quotient did
      not differ. Minor but significant elevations in serum levels of GH and cortisol
      were observed after ghrelin infusion. CONCLUSIONS: Administration of exogenous
      ghrelin causes insulin resistance in muscle and stimulates lipolysis; these
      effects are likely to be direct, although a small contribution of GH and cortisol
      cannot be excluded.

PMID- 18042652
TI  - Disturbances of calcium homeostasis consistent with mild primary
      hyperparathyroidism in premenopausal women and associated morbidity.
AB  - CONTEXT: Primary hyperparathyroidism (PHPT) and associated morbidity are
      comprehensively assessed in elderly females; however, less is known of the
      disease in younger women. OBJECTIVES: Our objectives were to estimate the
      prevalence of mild disturbances in calcium homeostasis, which could be analogous
      with early PHPT, in a premenopausal population, and determine the potential
      presence of associated morbidity. DESIGN: Initial results from this longitudinal
      study are from 2002-2004. SETTING: We conducted a population-based screening of
      serum (s)-calcium in conjunction with routine mammography. PARTICIPANTS:
      Participants included premenopausal women, 40-50 yr of age (n = 1900). Cases
      fulfilling previously evaluated biochemical criteria for PHPT (n=214) were
      matched to controls (n = 214). MAIN OUTCOME MEASUREMENTS: All participants
      underwent investigation, including screening of parameters of calcium
      homeostasis, dual x-ray absorptiometry, and body mass index assessment, and
      filled out extensive health and quality of life (SF-36) questionnaires.
      Participants were divided into four groups depending on the relation between s
      calcium/intact PTH. Statistical comparisons between cases and controls as well as
      among the four groups were performed to evaluate morbidity. RESULTS: The
      prevalence of assumed mild PHPT, i.e. inappropriate intact PTH value in relation
      to total s-calcium, was estimated to be 5.1% (n = 96). Women with mild
      disturbances in calcium homeostasis had statistically significant lower bone
      mineral density in the proximal femur and femoral neck, higher body mass index,
      and lower scores for vitality and general health in the analysis of SF-36.
      CONCLUSIONS: Mild disturbances in calcium homeostasis in premenopausal women were
      more prevalent than previously thought and were associated with obesity, lower
      bone mineral density, and decreased quality of life.

PMID- 18042654
TI  - Using routine data to measure ethnic differentials in access to coronary
      revascularization.
AB  - BACKGROUND: Ethnic inequalities in access to health services are difficult to
      monitor and address because of limited data. Within the health service, ethnicity
      data have been poor quality, partly because they are not seen as useful. METHODS:
      The analysis related age- and sex-standardized coronary revascularization
      procedures to defined measures of need, using proportional ratios derived from
      Hospital Episode Statistics records for London residents admitted to any hospital
      nationally in 2002-03 or 2003-04. RESULTS: Although 2001 Ethnicity Categories
      were mandatory for the NHS from April 2001, by 2003-04 >20% of coronary heart
      disease (CHD) records still had no ethnic category coded. Hospital admission for
      CHD and revascularization by ethnicity varied widely, following known patterns of
      CHD incidence and mortality. There is much less variation between ethnic groups
      when comparing revascularization rate relative with CHD admission rates (whether
      all or emergencies). However, Bangladeshi patients had only two-thirds
      [proportional ratio 66.8, 95% confidence interval (CI) 60.7-73.3] and Black
      Caribbean and Black African patients four-fifths (proportional ratios 80.5, 72.0
      89.9 and 80.7, 68.0-95.2, respectively) the revascularization rate in comparison
      with apparent need as the general population. CONCLUSION: Even with imperfect
      data, the analysis of routine data can identify inequalities that warrant further
      investigation.

PMID- 18042655
TI  - Influence of feedback schedule in motor performance and learning of a lumbar
      multifidus muscle task using rehabilitative ultrasound imaging: a randomized
      clinical trial.
AB  - BACKGROUND AND PURPOSE: Low back pain (LBP) may be associated with inadequate
      multifidus muscle function. Varying the frequency and timing of feedback may
      enhance acquisition and retention of multifidus muscle recruitment during
      exercise. SUBJECTS: Subjects without LBP (n=30) were randomly assigned to a
      constant (CON) or variable (VAR) feedback group. Twenty-eight subjects (mean
      age=28 years, SD=8.0; mean body mass index=24 kg/m(2), SD=0.70) completed
      training, and 23 completed retention testing. METHODS: Eight training sessions
      over 4 weeks included multifidus muscle exercise with rehabilitative ultrasound
      imaging (RUSI) feedback. Retention was assessed at 1 week and >or=1 month.
      RESULTS: At the start, both groups had similar performances of multifidus muscle
      recruitment (Fisher exact test, P=.26). Early in training, the CON group had good
      success (mean=80%) that was maintained at session 8 (mean=84%), with no
      difference between sessions 1 and 8 (Wilcoxon signed rank test, P=.19, 95%
      confidence interval [CI]=-9%, 42%). The VAR group gradually increased success
      (Wilcoxon signed rank test, P=.002, 95% CI=17%, 59%) between sessions 1 and 8.
      Both groups sustained their session 8 success when tested for short-term
      retention at 1 week (CON group: Wilcoxon signed rank test, P=.79; VAR group:
      Wilcoxon signed rank test, P=.36). At the long-term retention test, the VAR group
      outperformed the CON group (Wilcoxon score test, P=.04), indicating superior
      motor learning. DISCUSSION AND CONCLUSION: Variable feedback provided by RUSI
      resulted in greater success in lumbar multifidus muscle recruitment up to 3 to 4
      months after training.

PMID- 18042653
TI  - Increased melatonin and delayed offset in menopausal depression: role of years
      past menopause, follicle-stimulating hormone, sleep end time, and body mass
      index.
AB  - CONTEXT: The constellation of endocrine patterns accompanying menopausal
      depression remains incompletely characterized. OBJECTIVE: Our objective was to
      test the hypothesis that the amplitude or phase (timing) of melatonin circadian
      rhythms differs in menopausal depressed patients (DP) vs. normal controls women
      (NC). DESIGN: We measured plasma melatonin every 30 min from 1800-1000 h in dim
      light (<30 lux) or dark, serum gonadotropins and steroids (1800 and 0600 h), and
      mood (Hamilton and Beck depression ratings). SETTING: The study was conducted at
      a university hospital. PARTICIPANTS AND SETTING: Twenty-nine (18 NC, 11 DP) peri-
      or postmenopausal women participated. MAIN OUTCOME MEASURES: We measured plasma
      melatonin (onset, offset, synthesis offset, duration, peak concentration, and
      area under the curve) and mood. RESULTS: Multi- and univariate analyses of
      covariance showed that melatonin offset time was delayed (P = 0.045) and plasma
      melatonin was elevated in DP compared with NC (P = 0.044) across time intervals.
      Multiple regression analyses showed that years past menopause predicted melatonin
      duration and that melatonin duration, body mass index, years past menopause, FSH
      level, and sleep end time were significant predictors of baseline Hamilton (P =
      0.0003) and Beck (P = 0.00004) depression scores. CONCLUSIONS: Increased
      melatonin secretion that is phase delayed into the morning characterized
      menopausal DP vs. NC. Years past menopause, FSH, sleep end time, and body mass
      index may modulate effects of altered melatonin secretion in menopausal
      depression.

PMID- 18042656
TI  - Implementing an integrated electronic outcomes and electronic health record
      process to create a foundation for clinical practice improvement.
AB  - BACKGROUND AND PURPOSE: Improving clinical outcomes requires continuous
      measurement and interpretation in conjunction with treatment process and patient
      characteristics. The purposes of this study were: (1) to describe implementation
      and integration of electronic functional status outcomes into an electronic
      health record (EHR) for the promotion of clinical practice improvement processes
      and (2) to examine the effect of ongoing outcomes data collection in a large
      physical therapy service in relation to patient and clinic burden. SUBJECTS: Data
      were examined from 21,523 adult patients (mean age=50.6 years, SD=16.3, range=18
      99; 58.9% women, 41.1% men) referred for physical therapist management of
      neuromusculoskeletal disorders. METHODS: Process and patient characteristic data
      were entered into the EHR. OUTCOMES: data collected using computerized adaptive
      testing technology in 11 outpatient clinics were integrated into the EHR. The
      effect of data collection was assessed by measuring the participation rate,
      completion rate, and data entry time. Qualitative assessment of the
      implementation process was conducted. RESULTS: After 1 year, the average
      participation rate per clinic was 79.8% (range=52.7%-100%), the average
      completion rate per clinic was 45.1% (range=19.3%-64.7%), and the average data
      entry time per patient (minutes:seconds) was 03:37 (SD=02:19). Maximum estimate
      of average administrative time per patient was 9.6% of overall episode time.
      Barriers to and facilitators of the implementation process were identified.
      DISCUSSION AND CONCLUSION: The results indicate that routine collection of
      outcome data is realistic in a large public physical therapy service and can be
      successfully integrated with EHR data to produce a valuable clinical practice
      improvement platform for service evaluation and outcomes research. Participation
      and completion rate goals of 90% and 65%, respectively, appear to be feasible.

PMID- 18042657
TI  - Effect of focus of attention and age on motor acquisition, retention, and
      transfer: a randomized trial.
AB  - BACKGROUND AND PURPOSE: Adult participants benefit more from external focus than
      internal focus when learning a new motor skill. Because learners from different
      age groups use different learning strategies, the purpose of this study was to
      investigate whether the effect of attention focus varies among children and
      adults. SUBJECTS AND METHODS: Thirty-four children and 32 adults were randomly
      assigned to internal or external focus-of-attention practice groups. Throwing
      darts toward a static target, participants performed 50 acquisition trials, 20
      retention trials, and 20 transfer trials. RESULTS: The results indicate that
      focus of attention varies between children and adults in accuracy and variability
      in the acquisition phase and in accuracy in the transfer phase. No interactions
      were found in the retention phase. DISCUSSION AND CONCLUSION: The findings
      suggest that external focus is more effective than internal focus in adults;
      therefore, physical therapists should instruct adult clients to focus their
      attention externally to facilitate motor learning. Physical therapists working
      with children should perhaps direct the client's attention internally; however,
      further study is needed.

PMID- 18042658
TI  - Chemical basis of glycine riboswitch cooperativity.
AB  - The glycine binding riboswitch forms a unique tandem aptamer structure that binds
      glycine cooperatively. We employed nucleotide analog interference mapping (NAIM)
      and mutagenesis to explore the chemical basis of glycine riboswitch
      cooperativity. Based on the interference pattern, at least two sites appear to
      facilitate cooperative tertiary interactions, namely, the minor groove of the P1
      helix from aptamer 1 and the major groove of the P3a helix from both aptamers.
      Mutation of these residues altered both the cooperativity and binding affinity of
      the riboswitch. The data support a model in which the P1 helix of the first
      aptamer participates in a tertiary interaction important for cooperativity, while
      nucleotides in the P1 helix of the second aptamer interface with the expression
      platform. These data have direct analogy to well-characterized mutations in
      hemoglobin, which provides a framework for considering cooperativity in this RNA
      based system.

PMID- 18042659
TI  - The demise of anti IL-5 for asthma, or not.

PMID- 18042660
TI  - Classification of diffuse lung disease in infants: the reality of groups.

PMID- 18042661
TI  - Lung cancer chemoprevention with inhaled corticosteroids?

PMID- 18042662
TI  - KATP channel-deficient pancreatic beta-cells are streptozotocin resistant because
      of lower GLUT2 activity.
AB  - In wild-type mice, a single injection of streptozotocin (STZ, 200 mg/kg body wt)
      caused within 4 days severe hyperglycemia, hypoinsulinemia, significant glucose
      intolerance, loss of body weight, and the disappearance of pancreatic beta-cells.
      However, in ATP-sensitive K(+) channel (K(ATP) channel)-deficient mice (Kir6.2(-/
      ) mice), STZ had none of these effects. Exposing isolated pancreatic islets to
      STZ caused severe damage in wild-type but not in Kir6.2(-/-) islets. Following a
      single injection, plasma STZ levels were slightly less in Kir6.2(-/-) mice than
      in wild-type mice. Despite the difference in plasma STZ, wild-type and Kir6.2(-/
      ) liver accumulated the same amount of STZ, whereas Kir6.2(-/-) pancreas
      accumulated 4.1-fold less STZ than wild-type pancreas. Kir6.2(-/-) isolated
      pancreatic islets also transported less glucose than wild-type ones.
      Quantification of glucose transporter 2 (GLUT2) protein content by Western blot
      using an antibody with an epitope in the extracellular loop showed no significant
      difference in GLUT2 content between wild-type and Kir6.2(-/-) pancreatic islets.
      However, visualization by immunofluorescence with the same antibody gave rise to
      32% less fluorescence in Kir6.2(-/-) pancreatic islets. The fluorescence
      intensity using another antibody, with an epitope in the COOH terminus, was 5.6
      times less in Kir6.2(-/-) than in wild-type pancreatic islets. We conclude that
      1) Kir6.2(-/-) mice are STZ resistant because of a decrease in STZ transport by
      GLUT2 in pancreatic beta-cells and 2) the decreased transport is due to a
      downregulation of GLUT2 activity involving an effect at the COOH terminus.

PMID- 18042663
TI  - Cannabinoids stimulate prostaglandin production by human gestational tissues
      through a tissue- and CB1-receptor-specific mechanism.
AB  - Endocannabinoids have been implicated in the mechanisms of implantation,
      maintenance of pregnancy, and parturition in women. Intrauterine prostaglandin
      production and actions are also critical in each of these mechanisms. Hence, we
      have evaluated the effects of cannabinoids on prostaglandin biosynthesis by human
      gestational membranes. Explants of term amnion and choriodecidua were established
      and treated with the endogenous endocannabinoids 2-arachidonoyl glycerol and
      anandamide, as well as the synthetic cannabinoid CP55,940, to determine their
      ability to modulate PGE(2) production. The explants were also treated with
      CP55,940 in the presence of either SR141716A (a potent and selective antagonist
      of the cannabinoid receptor CB1) or NS398 [a cyclooxygenase (COX)-2 inhibitor] to
      determine whether any observed stimulation of PGE(2) production was mediated
      through the CB1-receptor and/or COX-2 activity. All three cannabinoids caused a
      significant increase in PGE(2) production in the amnion but not in the
      choriodecidua. However, separated fetal (chorion) explants responded to
      cannabinoid treatment in a similar manner to amnion, whereas maternal (decidual)
      explants did not. The enhanced PGE(2) production caused by CP55,940 was abrogated
      by cotreatment with either SR141716A or NS398, illustrating that the cannabinoid
      action on prostaglandin production in fetal membranes is mediated by CB1 agonism
      and COX-2. Data from Western blotting show that cannabinoid treatment results in
      the upregulation of COX-2 expression. This study demonstrates a potential role
      for endocannabinoids in the modulation of prostaglandin production in late human
      pregnancy, with potentially important implications for the timing and progression
      of term and preterm labor and membrane rupture.

PMID- 18042664
TI  - Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases
      glucose utilization in the heart.
AB  - Stearoyl-CoA desaturase (SCD) is a lipogenic enzyme that catalyzes the synthesis
      of monounsaturated fatty acids (FA). SCD1 deficiency activates metabolic pathways
      that promote FA beta-oxidation and decrease lipogenesis in liver. In the present
      study, we show that FA transport and oxidation are decreased, whereas glucose
      uptake and oxidation are increased in the heart of SCD1(-/-) mice. Protein levels
      of FA transport proteins such as FA translocase/CD36 and FA transport protein as
      well as activity of carnitine palmitoyltransferase 1, the rate-limiting enzyme
      for mitochondrial fat oxidation, were significantly lower in the heart of SCD1(-/
      ) mice compared with SCD1(+/+) mice. Consequently, the rate of palmitoyl-CoA
      oxidation was decreased significantly in the heart of SCD1(-/-) mice. mRNA levels
      of peroxisome proliferator-activated receptor-alpha, a key transcription factor
      controlling genes of FA oxidation, were significantly reduced in SCD1(-/-) mice.
      Phosphorylation of insulin receptor substrate-1 (IRS-1) and the association of
      alphap85 subunit of phosphatidylinositol 3-kinase with IRS-1 were significantly
      higher under both basal and insulin-stimulated conditions in SCD1(-/-) hearts.
      This increased insulin sensitivity translated to a 1.8-fold greater 2
      deoxyglucose uptake and 2-fold higher rate of glucose oxidation in the myocardium
      compared with SCD1(+/+) counterparts. The results suggest that SCD1 deficiency
      causes a shift in cardiac substrate utilization from FA to glucose by
      upregulating insulin signaling, decreasing FA availability, and reducing
      expression of FA oxidation genes in the heart. This increase in cardiac insulin
      sensitivity and glucose utilization due to SCD1 deficiency could prove
      therapeutic in pathological conditions such as obesity that are characterized by
      skewed cardiac substrate utilization.

PMID- 18042665
TI  - Effect of sex differences on human MEF2 regulation during endurance exercise.
AB  - Women exhibit an enhanced capability for lipid metabolism during endurance
      exercise compared with men. The underlying regulatory mechanisms behind this sex
      related difference are not well understood but may comprise signaling through a
      myocyte enhancer factor 2 (MEF2) regulatory pathway. The primary purpose of this
      study, therefore, was to investigate the protein signaling of MEF2 regulatory
      pathway components at rest and during 90 min of bicycling exercise at 60%
      Vo(2peak) in healthy, moderately trained men (n = 8) and women (n = 9) to
      elucidate the potential role of these proteins in substrate utilization during
      exercise. A secondary purpose was to screen for mRNA expression of MEF2 isoforms
      and myogenic regulatory factor (MRF) family members of transcription factors at
      rest and during exercise. Muscle biopsies were obtained before and immediately
      after exercise. Nuclear AMP-activated protein kinase-alpha (alphaAMPK) Thr(172)
      (P < 0.001), histone deacetylase 5 (HDAC5) Ser(498) (P < 0.001), and MEF2 Thr (P
      < 0.01) phosphorylation increased with exercise. No significant sex differences
      were observed at rest or during exercise. At rest, no significant sex differences
      were observed in mRNA expression of the measured transcription factors. mRNA for
      transcription factors MyoD, myogenin, MRF4, MEF2A, MEF2C, MEF2D, and peroxisome
      proliferator-activated receptor-gamma coactivator 1alpha (PGC1alpha) were
      significantly upregulated by exercise. Of these, MEF2A mRNA increased 25%
      specifically in women (P < 0.05), whereas MEF2D mRNA tended to increase in men (P
      = 0.11). Although minor sex differences in mRNA expression were observed, the
      main finding of the present study was the implication of a joint signaling action
      of AMPK, HDAC5, and PGC1alpha on MEF2 in the immediate regulatory response to
      endurance exercise. This signaling response was independent of sex.

PMID- 18042666
TI  - Connexin-32 acts as a downregulator of growth of thyroid gland.
AB  - Thyroid epithelial cells communicate through gap junctions formed from connexin
      (Cx)32, Cx43, and Cx26. We previously reported that reexpression of Cx32 in "gap
      junction-deficient" FRTL-5 and FRT thyroid cell lines induces a reduction of cell
      proliferation rate and an activation of expression of cell differentiation. The
      present study aimed at determining whether Cx32 could exert similar regulatory
      functions in vivo. We investigated morphological and functional characteristics
      of thyroid gland of Cx32-deficient mice (Cx32-KO), mice overexpressing Cx32
      selectively in the thyroid (Cx32-T+), and Cx32-KO mice with a thyroid-selective
      Cx32 complementation obtained by crossing Cx32-KO and Cx32-T+ mice. In basal
      conditions, Cx32-KO mice did not present any detectable thyroid alteration,
      whereas Cx32-T+ mice showed a thyroid hypoplasia (20% reduction) associated with
      a slight increase in thyroid functional activity. Under thyrotropin stimulation
      (following sodium perchlorate treatment), Cx32-KO mice developed a larger goiter
      (< or =65% increase) than wild-type littermates, whereas Cx32-T+ mice exhibited
      the same thyroid hyperplasia as wild-type mice. Restoration of Cx32 expression in
      the thyroid of Cx32-KO mice abrogated the thyroid growth increase related to Cx32
      deficiency. All together, these data show that Cx32 acts as a downregulator of
      growth of thyroid gland; an excess of Cx32 limits growth of thyroid cells in the
      basal state, whereas a lack of Cx32 confers an additional growth potential to TSH
      stimulated thyroid cells.

PMID- 18042667
TI  - Kei on GSK: a contribution by the 2007 recipient of the Young Scientist Award.

PMID- 18042668
TI  - In vivo regulation of phenylalanine hydroxylation to tyrosine, studied using
      enrichment in apoB-100.
AB  - Phenylalanine hydroxylation is necessary for the conversion of phenylalanine to
      tyrosine and disposal of excess phenylalanine. Studies of in vivo regulation of
      phenylalanine hydroxylation suffer from the lack of a method to determine
      intrahepatocyte enrichment of phenylalanine and tyrosine. apoB-100, a hepatic
      export protein, is synthesized from intrahepatocyte amino acids. We designed an
      in vivo multi-isotope study, [(15)N]phenylalanine and [2H2]tyrosine to determine
      rates of phenylalanine hydroxylation from plasma enrichments in free amino acids
      and apoB-100. For independent verification of apoB-100 as a reflection of
      enrichment in the intrahepatocyte pool, [1-(13)C]lysine was used as an indicator
      amino acid (IAA) to measure in vivo changes in protein synthesis in response to
      tyrosine supplementation. Adult men (n = 6) were fed an amino acid-based diet
      with low phenylalanine (9 mg.kg(-1).day(-1), 4.54 mumol.kg(-1).,h(-1)) and seven
      graded intakes of tyrosine from 2.5 (deficient) to 12.5 (excess) mg.kg(-1).day(
      1). Gas chromatography-quadrupole mass spectrometry did not detect any tracer in
      apoB-100 tyrosine. A new and more sensitive method to measure label enrichment in
      proteins using isotope ratio mass spectrometry demonstrated that phenylalanine
      hydroxylation measured in apoB-100 decreased linearly in response to increasing
      tyrosine intake and reached a break point at 6.8 mg.kg(-1).day(-1). IAA oxidation
      decreased with increased tyrosine intake and reached a break point at 6.0 mg.kg(
      1).day(-1). We conclude: apoB-100 is an accurate and useful measure of changes in
      phenylalanine hydroxylation; the synthesis of tyrosine via phenylalanine
      hydroxylation is regulated to meet the needs for protein synthesis; and that
      plasma phenylalanine does not reflect changes in protein synthesis.

PMID- 18042669
TI  - Efficiency of autoregulatory homeostatic responses to imposed caloric excess in
      lean men.
AB  - Obesity implies a failure of autoregulatory homeostatic responses to caloric
      excess. We studied the mechanisms, effectiveness, and limits of such responses in
      six lean (21.9 +/- 1.3 kg/m(2)), healthy men based in a metabolic suite for 17 wk
      of progressive intermittent overfeeding (OF) (3 wk, baseline; 3 wk, 20% OF; 1 wk,
      ad libitum; 3 wk, 40% OF; 1 wk, ad libitum; 3 wk, 60% OF; 3 wk, ad libitum). Body
      composition was assessed by a four-compartment model using dual X-ray
      absorptiometry, deuterium dilution, and plethysmography. Magnetic resonance
      imaging assessed subcutaneous/visceral fat at abdominal level at baseline and at
      the end of 60% OF. Energy intake was assessed throughout, energy expenditure (EE)
      and substrate oxidation rates were measured repeatedly by whole body calorimetry
      (calEE), and free-living EE (TEE) was measured by doubly labeled water at
      baseline and after 60% OF. At the end of 60% OF, calEE and TEE had increased by
      just 11.4% (P = 0.001) and 16.2% (P = 0.001), respectively. Weight and body fat
      (fat mass) had increased by 5.98 kg (8.8%, P = 0.001) and 3.31 kg (22.6%, P =
      0.01), respectively. The relative increase in visceral fat (32.6%, P = 0.02)
      exceeded that of subcutaneous fat (13.3%, P = 0.002) in the abdominal region. The
      computed energy cost of tissue accretion differed from the excess ingested by
      only 13.1% (using calEE) and 11.6% (using TEE), indicating an absence of
      effective dissipative mechanisms. We conclude that elevations in EE provide very
      limited autoregulatory capacity in body weight regulation, and that regulation
      must be dominated by hypothalamic modulation of energy intake. This result
      supports present conclusions from genetic studies in which all known causes of
      human obesity are related to defects in the regulation of appetite.

PMID- 18042670
TI  - The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding
      capacity in human skeletal muscle.
AB  - AS160 is an Akt substrate of 160 kDa implicated in the regulation of both insulin
      and contraction-mediated GLUT4 translocation and glucose uptake. The effects of
      aerobic exercise and subsequent insulin stimulation on AS160 phosphorylation and
      the binding capacity of 14-3-3, a novel protein involved in the dissociation of
      AS160 from GLUT4 vesicles, in human skeletal muscle are unknown. Hyperinsulinemic
      euglycemic clamps were performed on seven men at rest and immediately and 3 h
      after a single bout of cycling exercise. Skeletal muscle biopsies were taken
      before and after the clamps. The insulin sensitivity index calculated during the
      final 30 min of the clamp was 8.0 +/- 0.8, 9.1 +/- 0.5, and 9.2 +/- 0.8 for the
      rest, postexercise, and 3-h postexercise trials, respectively. AS160
      phosphorylation increased immediately after exercise and remained elevated 3 h
      after exercise. In contrast, the 14-3-3 binding capacity of AS160 and
      phosphorylation of Akt and AMP-activated protein kinase were only increased
      immediately after exercise. Insulin increased AS160 phosphorylation and 14-3-3
      binding capacity and insulin receptor substrate-1 and Akt phosphorylation, but
      the response to insulin was not enhanced by prior exercise. In conclusion, the 14
      3-3 binding capacity of AS160 is increased immediately after acute exercise in
      human skeletal muscle, but this is not maintained 3 h after exercise completion
      despite sustained AS160 phosphorylation. Insulin increases AS160 phosphorylation
      and 14-3-3 binding capacity, but prior exercise does not appear to enhance the
      response to insulin.

PMID- 18042671
TI  - Familial aggregation of hypospadias: a cohort study.
AB  - Hypospadias is one of the most common birth defects. However, its etiology
      remains largely unknown. The authors investigated the contribution of genetic and
      environmental factors to familial aggregation of hypospadias. Using Danish health
      registers, they identified 5,380 boys diagnosed with hypospadias in a cohort of
      1,201,790 boys born in 1973-2005. Using binomial log-linear regression, they
      estimated recurrence risk ratios of hypospadias for male twin pairs and first-,
      second-, and third-degree relatives of a hypospadias case, which were 50.8 (95%
      confidence interval [CI]: 34.2, 75.5), 11.6 (95% CI: 9.75, 13.7), 3.27 (95% CI:
      2.47, 4.34), and 1.33 (95% CI: 0.94, 1.88), respectively. Recurrence risk ratios
      did not differ for family members of a hypospadias case related to the same
      degree. In addition, the authors found no difference in the recurrence risk ratio
      for maternal compared with paternal second- and third-degree relatives of a
      hypospadias case. In conclusion, hypospadias was found to have a strong familial
      component and also to aggregate within more-distant relatives. Importantly,
      hypospadias was equally transmitted through the paternal and maternal sides of a
      family, and recurrence risk ratios for brothers and sons of a hypospadias case
      were similar. These findings indicate that genetic rather than intrauterine
      environmental factors have a principal role in causing familial hypospadias.

PMID- 18042672
TI  - Gestational age, birth weight, intrauterine growth, and the risk of epilepsy.
AB  - The authors evaluated the association between gestational age, birth weight,
      intrauterine growth, and epilepsy in a population-based cohort of 1.4 million
      singletons born in Denmark (1979-2002). A total of 14,334 inpatients (1979-2002)
      and outpatients (1995-2002) with epilepsy were registered in the Danish National
      Hospital Register. Children who were potentially growth restricted were
      identified through two methods: 1) sex-, birth-order-, and gestational-age
      specific z score of birth weight; and 2) deviation from the expected birth weight
      estimated based on the birth weight of an older sibling. The incidence rates of
      epilepsy increased consistently with decreasing gestational age and birth weight.
      The incidence rate ratios of epilepsy in the first year of life were more than
      fivefold among children born at 22-32 weeks compared with 39-41 weeks and among
      children whose birth weight was <2,000 g compared with 3,000-3,999 g. The
      association was modified by age but remained into early adulthood. Incidence rate
      ratios of epilepsy were increased among children identified as growth restricted
      according to either of the two methods. In conclusion, short gestational age, low
      birth weight, and intrauterine growth restriction are associated with an
      increased risk of epilepsy.

PMID- 18042673
TI  - Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and
      ADAMTS5.
AB  - Aggrecanases are now believed to be the principal proteinases responsible for
      aggrecan degradation in osteoarthritis. Given their potential as a drug target,
      we solved crystal structures of the two most active human aggrecanase isoforms,
      ADAMTS4 and ADAMTS5, each in complex with bound inhibitor and one wherein the
      enzyme is in apo form. These structures show that the unliganded and inhibitor
      bound enzymes exhibit two essentially different catalytic-site configurations: an
      autoinhibited, nonbinding, closed form and an open, binding form. On this basis,
      we propose that mature aggrecanases exist as an ensemble of at least two isomers,
      only one of which is proteolytically active.

PMID- 18042674
TI  - Energetic rationale for an unexpected and abrupt reversal of guanidinium chloride
      induced unfolding of peptide deformylase.
AB  - Peptide deformylase (PDF) catalyzes the removal of formyl group from the N
      terminal methionine residues of nascent proteins in prokaryotes, and this enzyme
      is a high priority target for antibiotic design. In pursuit of delineating the
      structural-functional features of Escherichia coli PDF (EcPDF), we investigated
      the mechanistic pathway for the guanidinium chloride (GdmCl)-induced unfolding of
      the enzyme by monitoring the secondary structural changes via CD spectroscopy.
      The experimental data revealed that EcPDF is a highly stable enzyme, and it
      undergoes slow denaturation in the presence of varying concentrations of GdmCl.
      The most interesting aspect of these studies has been the abrupt reversal of the
      unfolding pathway at low to moderate concentrations of the denaturant, but not at
      high concentration. An energetic rationale for such an unprecedented feature in
      protein chemistry is offered.

PMID- 18042675
TI  - Crystal structure of Mycobacterium tuberculosis LrpA, a leucine-responsive global
      regulator associated with starvation response.
AB  - The bacterial leucine-responsive regulatory protein (Lrp) is a global
      transcriptional regulator that controls the expression of many genes during
      starvation and the transition to stationary phase. The Mycobacterium tuberculosis
      gene Rv3291c encodes a 150-amino acid protein (designated here as Mtb LrpA) with
      homology with Escherichia coli Lrp. The crystal structure of the native form of
      Mtb LrpA was solved at 2.1 A. The Mtb LrpA structure shows an N-terminal DNA
      binding domain with a helix-turn-helix (HTH) motif, and a C-terminal regulatory
      domain. In comparison to the complex of E. coli AsnC with asparagine, the
      effector-binding pocket (including loop 100-106) in LrpA appears to be largely
      preserved, with hydrophobic substitutions consistent with its specificity for
      leucine. The effector-binding pocket is formed at the interface between adjacent
      dimers, with an opening to the core of the octamer as in AsnC, and an additional
      substrate-access channel opening to the outer surface of the octamer. Using
      electrophoretic mobility shift assays, purified Mtb LrpA protein was shown to
      form a protein-DNA complex with the lat promoter, demonstrating that the lat
      operon is a direct target of LrpA. Using computational analysis, a putative motif
      is identified in this region that is also present upstream of other operons
      differentially regulated under starvation. This study provides insights into the
      potential role of LrpA as a global regulator in the transition of M. tuberculosis
      to a persistent state.

PMID- 18042676
TI  - The hypothetical protein Atu4866 from Agrobacterium tumefaciens adopts a
      streptavidin-like fold.
AB  - Atu4866 is a 79-residue conserved hypothetical protein of unknown function from
      Agrobacterium tumefaciens. Protein sequence alignments show that it shares > or
      =60% sequence identity with 20 other hypothetical proteins of bacterial origin.
      However, the structures and functions of these proteins remain unknown so far. To
      gain insight into the function of this family of proteins, we have determined the
      structure of Atu4866 as a target of a structural genomics project using solution
      NMR spectroscopy. Our results reveal that Atu4866 adopts a streptavidin-like fold
      featuring a beta-barrel/sandwich formed by eight antiparallel beta-strands.
      Further structural analysis identified a continuous patch of conserved residues
      on the surface of Atu4866 that may constitute a potential ligand-binding site.

PMID- 18042677
TI  - The yeast Ski complex is a hetero-tetramer.
AB  - The yeast Ski complex assists the exosome in the degradation of mRNA. The Ski
      complex consists of three components; Ski2, Ski3, and Ski8, believed to be
      present in a 1:1:1 stoichiometry. Measuring the mass of intact isolated
      endogenously expressed Ski complexes by native mass spectrometry we unambiguously
      demonstrate that the Ski complex has a hetero-tetrameric stoichiometry consisting
      of one copy of Ski2 and Ski3 and two copies of Ski8. To validate the
      stoichiometry of the Ski complex, we performed tandem mass spectrometry. In these
      experiments one Ski8 subunit was ejected concomitant with the formation of a
      Ski2/Ski3/Ski8 fragment, confirming the proposed stoichiometry. To probe the
      topology of the Ski complex we disrupted the complex and mass analyzed the thus
      formed subcomplexes, detecting Ski8-Ski8, Ski2-Ski3, Ski8-Ski2, and Ski8-Ski8
      Ski2. Combining all data we construct an improved structural model of the Ski
      complex.

PMID- 18042678
TI  - Robust recognition of zinc binding sites in proteins.
AB  - Metals play a variety of roles in biological processes, and hence their presence
      in a protein structure can yield vital functional information. Because the
      residues that coordinate a metal often undergo conformational changes upon
      binding, detection of binding sites based on simple geometric criteria in
      proteins without bound metal is difficult. However, aspects of the
      physicochemical environment around a metal binding site are often conserved even
      when this structural rearrangement occurs. We have developed a Bayesian
      classifier using known zinc binding sites as positive training examples and
      nonmetal binding regions that nonetheless contain residues frequently observed in
      zinc sites as negative training examples. In order to allow variation in the
      exact positions of atoms, we average a variety of biochemical and biophysical
      properties in six concentric spherical shells around the site of interest. At a
      specificity of 99.8%, this method achieves 75.5% sensitivity in unbound proteins
      at a positive predictive value of 73.6%. We also test its accuracy on predicted
      protein structures obtained by homology modeling using templates with 30%-50%
      sequence identity to the target sequences. At a specificity of 99.8%, we
      correctly identify at least one zinc binding site in 65.5% of modeled proteins.
      Thus, in many cases, our model is accurate enough to identify metal binding sites
      in proteins of unknown structure for which no high sequence identity homologs of
      known structure exist. Both the source code and a Web interface are available to
      the public at http://feature.stanford.edu/metals.

PMID- 18042679
TI  - Characterization of an exosite binding inhibitor of matrix metalloproteinase 13.
AB  - Matrix metalloproteinase 13 (MMP13) is a key enzyme implicated in the degradation
      of the extracellular matrix in osteoarthritis. Clinical administration of broad
      spectrum MMP inhibitors such as marimastat has been implicated in severe musculo
      skeletal side effects. Consequently, research has been focused on designing
      inhibitors that selectively inhibit MMP13, thereby circumventing musculo-skeletal
      toxicities. A series of pyrimidine dicarboxamides were recently shown to be
      highly selective inhibitors of MMP13 with a novel binding mode. We have applied a
      molecular ruler to this exosite by dual inhibition studies involving a potent
      dicarboxamide in the presence of two metal chelators of different sizes. A larger
      hydroxamate mimic overlaps and antagonizes binding of the dicarboxamide to the
      exosite whereas the much smaller acetohydroxamate synergizes with the
      dicarboxamide. These studies elucidate the steric requirement for compounds that
      fit exclusively into the active site, a mandate for generating highly selective
      MMP13 inhibitors.

PMID- 18042680
TI  - Amyloid-a state in many guises: survival of the fittest fibril fold.
AB  - Under appropriate conditions, essentially all proteins are able to aggregate to
      form long, well-ordered and beta-sheet-rich arrays known as amyloid-like fibrils.
      These fibrils consist of varying numbers of intertwined protofibrils and can for
      any given protein exhibit a wealth of different forms at the ultrastructural
      level. Traditionally, this structural variability or polymorphism has been
      attributed to differences in the assembly of a common protofibril structure.
      However, recent work on glucagon, insulin, and the Abeta peptide suggests that
      this polymorphism can occur at the level of secondary structure. Simple
      variations in either solvent conditions such as temperature, protein
      concentration, and ionic strength or external mechanical influences such as
      agitation can lead to formation of fibrils with markedly different
      characteristics. In some cases, these characteristics can be passed on to new
      fibrils in a strain-specific manner, similar to what is known for prions. The
      preferred structure of fibrils formed can be explained in terms of selective
      pressure and survival of the fittest; the most populated types of fibrils we
      observe at the end of an experiment are those that had the fastest overall growth
      rate under the given conditions. Fibrillar polymorphism is probably a consequence
      of the lack of structural restraints on a nonfunctional conformational state.

PMID- 18042681
TI  - Chemical synthesis and 1H-NMR 3D structure determination of AgTx2-MTX chimera, a
      new potential blocker for Kv1.2 channel, derived from MTX and AgTx2 scorpion
      toxins.
AB  - Agitoxin 2 (AgTx2) is a 38-residue scorpion toxin, cross-linked by three
      disulfide bridges, which acts on voltage-gated K(+) (Kv) channels. Maurotoxin
      (MTX) is a 34-residue scorpion toxin with an uncommon four-disulfide bridge
      reticulation, acting on both Ca(2+)-activated and Kv channels. A 39-mer chimeric
      peptide, named AgTx2-MTX, was designed from the sequence of the two toxins and
      chemically synthesized. It encompasses residues 1-5 of AgTx2, followed by the
      complete sequence of MTX. As established by enzyme cleavage, the new AgTx2-MTX
      molecule displays half-cystine pairings of the type C1-C5, C2-C6, C3-C7, and C4
      C8, which is different from that of MTX. The 3D structure of AgTx2-MTX solved by
      (1)H-NMR, revealed both alpha-helical and beta-sheet structures, consistent with
      a common alpha/beta scaffold of scorpion toxins. Pharmacological assays of AgTx2
      MTX revealed that this new molecule is more potent than both original toxins in
      blocking rat Kv1.2 channel. Docking simulations, performed with the 3D structure
      of AgTx2-MTX, confirmed this result and demonstrated the participation of the N
      terminal domain of AgTx2 in its increased affinity for Kv1.2 through additional
      molecular contacts. Altogether, the data indicated that replacement of the N
      terminal domain of MTX by the one of AgTx2 in the AgTx2-MTX chimera results in a
      reorganization of the disulfide bridge arrangement and an increase of affinity to
      the Kv1.2 channel.

PMID- 18042682
TI  - Crystal structure of an archaeal Ski2p-like protein from Pyrococcus horikoshii
      OT3.
AB  - The Ski complex composed of Ski2p, Ski3p, and Ski8p plays an essential role in
      the 3' to 5' cytoplasmic mRNA degradation pathway in yeast. Ski2p is a putative
      RNA helicase, belonging in the DExD/H-box protein families and conserved in
      eukarya as well as in archaea. The gene product (Ph1280p) from the
      hyperthermophilic archaeon Pyrococcus horikoshii OT3 shows sequence homology with
      Ski2p, sharing 22.6% identical amino acids with a central region of Ski2p. In
      order to gain structural information about the Ski2p-like RNA helicase, we
      overproduced Ph1280p in Escherichia coli cells, and purified it to apparent
      homogeneity. Ph1280p exhibits DNA/RNA-dependent ATPase activity with an optimal
      temperature at approximately 90 degrees C. The crystal structure of Ph1280p has
      been solved at a resolution of 3.5 A using single-wavelength anomalous dispersion
      (SAD) and selenomethionyl (Se-Met)-substituted protein. Ph1280p comprises four
      subdomains; the two N-terminal subdomains (N1 and N2) fold into an RecA-like
      architecture with the conserved helicase motifs, while the two C-terminal
      subdomains (C1 and C2) fold into alpha-helical structures containing a winged
      helix (WH)-fold and helix-hairpin-helix (HhH)-fold, respectively. Although the
      structure of each of the Ph1280p subdomains can be individually superimposed on
      the corresponding domains in other helicases, such as the Escherichia coli DNA
      helicase RecQ, the relative orientation of the helicase and C-terminal subdomains
      in Ph1280p is significantly different from that of other helicases. This
      structural feature is implicated in substrate specificity for the Ski2-like
      helicase and would play a critical role in the 3' to 5' cytoplasmic mRNA
      degradation in the Ski complex.

PMID- 18042683
TI  - Solution NMR studies of apo-mSin3A and -mSin3B reveal that the PAH1 and PAH2
      domains are structurally independent.
AB  - The evolutionarily conserved mammalian Sin3 (mSin3) transcriptional corepressor
      interacts with a diverse array of transcription factors mainly through two PAH
      (paired amphipathic helix) domains located near the N terminus. Previous studies
      suggested the possibility of interdomain interactions involving the PAH domains.
      Here, we show that the domains are structurally independent and the properties of
      the individual domains, such as the conformational heterogeneity and the ability
      of mSin3A PAH2 to homodimerize, are preserved in constructs that span both PAH
      domains. Our results thus suggest that the N-terminal segments of the Sin3
      proteins are broadly available for interactions with other proteins and that the
      PAH domains are organized into structurally independent modules. Our data also
      rule out any heterotypic association between the paralogous mSin3A and mSin3B
      proteins via interactions involving the mSin3A PAH2 domain.

PMID- 18042684
TI  - Modeling of protein binary complexes using structural mass spectrometry data.
AB  - In this article, we describe a general approach to modeling the structure of
      binary protein complexes using structural mass spectrometry data combined with
      molecular docking. In the first step, hydroxyl radical mediated oxidative protein
      footprinting is used to identify residues that experience conformational
      reorganization due to binding or participate in the binding interface. In the
      second step, a three-dimensional atomic structure of the complex is derived by
      computational modeling. Homology modeling approaches are used to define the
      structures of the individual proteins if footprinting detects significant
      conformational reorganization as a function of complex formation. A three
      dimensional model of the complex is constructed from these binary partners using
      the ClusPro program, which is composed of docking, energy filtering, and
      clustering steps. Footprinting data are used to incorporate constraints-positive
      and/or negative-in the docking step and are also used to decide the type of
      energy filter-electrostatics or desolvation-in the successive energy-filtering
      step. By using this approach, we examine the structure of a number of binary
      complexes of monomeric actin and compare the results to crystallographic data.
      Based on docking alone, a number of competing models with widely varying
      structures are observed, one of which is likely to agree with crystallographic
      data. When the docking steps are guided by footprinting data, accurate models
      emerge as top scoring. We demonstrate this method with the actin/gelsolin segment
      1 complex. We also provide a structural model for the actin/cofilin complex using
      this approach which does not have a crystal or NMR structure.

PMID- 18042685
TI  - Ixolaris binding to factor X reveals a precursor state of factor Xa heparin
      binding exosite.
AB  - Ixolaris is a two-Kunitz tick salivary gland tissue factor pathway inhibitor
      (TFPI). In contrast to human TFPI, Ixolaris specifically binds to factor Xa (FXa)
      heparin-binding exosite (HBE). In addition, Ixolaris interacts with zymogen FX.
      In the present work we characterized the interaction of Ixolaris with human FX
      quantitatively, and identified a precursor state of the heparin-binding exosite
      (proexosite, HBPE) as the Ixolaris-binding site on the zymogen. Gel-filtration
      chromatography demonstrated 1:1 complex formation between fluorescein-labeled
      Ixolaris and FX. Isothermal titration calorimetry confirmed that the binding of
      Ixolaris to FX occurs at stoichiometric concentrations in a reaction which is
      characteristically exothermic, with a favorable enthalpy (DeltaH) of -10.78
      kcal/mol. ELISA and plasmon resonance experiments also indicate that Ixolaris
      binds to plasma FX and FXa, or to recombinant Gla domain-containing FX/FXa with
      comparable affinities ( approximately 1 nM). Using a series of mutants on the
      HBPE, we identified the most important amino acids involved in zymogen/Ixolaris
      interaction-Arg-93 >>> Arg-165 > or = Lys-169 > Lys-236 > Arg-125-which was
      identical to that observed for FXa/Ixolaris interaction. Remarkably, Ixolaris
      strongly inhibited FX activation by factor IXa in the presence but not in the
      absence of factor VIIIa, suggesting a specific interference in the cofactor
      activity. Further, solid phase assays demonstrated that Ixolaris inhibits FX
      interaction with immobilized FVIIIa. Altogether, Ixolaris is the first inhibitor
      characterized to date that specifically binds to FX HBPE. Ixolaris may be a
      useful tool to study the physiological role of the FX HBPE and to evaluate this
      domain as a target for anticoagulant drugs.

PMID- 18042686
TI  - Functional flexibility of human cyclin-dependent kinase-2 and its evolutionary
      conservation.
AB  - Cyclin-dependent kinase 2 (CDK2) is the most thoroughly studied of the cyclin
      dependent kinases that regulate essential cellular processes, including the cell
      cycle, and it has become a model for studies of regulatory mechanisms at the
      molecular level. This contribution identifies flexible and rigid regions of CDK2
      based on temperature B-factors acquired from both X-ray data and molecular
      dynamics simulations. In addition, the biological relevance of the identified
      flexible regions and their motions is explored using information from the
      essential dynamics analysis related to conformational changes of CDK2 and
      knowledge of its biological function(s). The conserved regions of CMGC protein
      kinases' primary sequences are located in the most rigid regions identified in
      our analyses, with the sole exception of the absolutely conserved G13 in the tip
      of the glycine-rich loop. The conserved rigid regions are important for
      nucleotide binding, catalysis, and substrate recognition. In contrast, the most
      flexible regions correlate with those where large conformational changes occur
      during CDK2 regulation processes. The rigid regions flank and form a rigid
      skeleton for the flexible regions, which appear to provide the plasticity
      required for CDK2 regulation. Unlike the rigid regions (which as mentioned are
      highly conserved) no evidence of evolutionary conservation was found for the
      flexible regions.

PMID- 18042687
TI  - Non-operative breast pathology.

PMID- 18042688
TI  - Non-operative breast pathology: apocrine lesions.
AB  - Apocrine metaplasia is a very common finding in the female breast after the age
      of 25. It is so common that many people regard it as a normal component of the
      breast. This, however, is only really the case in apocrine sweat glands of the
      axilla and in the peri-areolar apocrine glands. The apocrine cell does, however,
      contribute to a number of different breast lesions, some of which are very taxing
      diagnostically; apocrine variants of both in-situ and invasive cancer are
      encountered. This review considers the common apocrine metaplastic lesions seen
      in fibrocystic change as well as apocrine adenoma, apocrine change within
      sclerosing adenosis, atypical apocrine lesions and apocrine malignancies.

PMID- 18042689
TI  - The histological diagnosis of metastases to the breast from extramammary
      malignancies.
AB  - This study aims to review histological and immunohistochemical features that are
      useful in the diagnosis of metastases to the breast. Histological features were
      compared between non-haematological metastases to the breast and 100 consecutive
      core biopsy specimens of primary invasive carcinomas of the breast. 18 non
      haematological metastases to the breast were diagnosed over a 10-year period
      (0.3% of malignant mammary tumours). Elastosis and carcinoma in situ were seen
      only in primary mammary cancers. Two-thirds of tumours had features raising the
      possibility of metastasis, such as clear cell carcinoma suggestive of renal
      origin and small cell carcinoma suggestive of pulmonary origin. The features
      observed in haematological metastases are also described. Immunohistochemical
      panels to distinguish mammary carcinoma (oestrogen receptor, gross cystic fluid
      protein-15) from common metastases to the breast, including carcinoma of the lung
      (thyroid transcription factor-1), malignant melanoma (S100, HMB45, melan-A) and
      ovarian serous papillary carcinoma (Wilms' tumour 1), are discussed. The
      pathologist has a key role in considering the diagnosis of metastasis to the
      breast if the histological features are unusual for a primary mammary tumour. The
      clinical history is vital in some cases. Immunohistochemistry plays a useful
      supplementary role.

PMID- 18042690
TI  - Contribution of the Epstein Barr virus to the molecular pathogenesis of Hodgkin
      lymphoma.
AB  - Although the morphology of the pathognomonic Reed-Sternberg cells of Hodgkin
      lymphoma (HL) was described over a century ago, it was not until recently that
      their origin from B lymphocytes was recognised. The demonstration that a
      proportion of cases of HL harbour the Epstein-Barr virus (EBV) and that its
      genome is monoclonal in these tumours suggests that the virus contributes to the
      development of HL in some cases. This review summarises current knowledge of the
      pathogenesis of HL with particular emphasis on the association with EBV.

PMID- 18042691
TI  - Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 and lymphoproliferative
      disorders.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8
      (HHV8), is a recent addition to the list of human viruses that are directly
      associated with lymphoproliferative disorders. KSHV was first shown to be
      involved in multicentric Castleman disease and primary effusion lymphoma (PEL).
      Subsequently, the virus was identified in solid lymphomas, often of extranodal
      sites, with morphological and immunophenotypic characteristics similar to those
      of PEL, and in other lymphoproliferative disorders with heterogeneous
      clinicopathological presentations. The recent advances in our understanding of
      the histology, immunophenotype and pathogenesis of these KSHV-associated
      lymphoproliferative disorders are reviewed.

PMID- 18042692
TI  - HIV infection and lymphoma.
AB  - The incidence of lymphoma in patients with HIV infection greatly exceeds that of
      the general population. The increased risk for lymphoma appears related to
      multiple factors, including the transforming properties of the retrovirus itself,
      the immunosuppression and cytokine dysregulation that results from the disease,
      and, most importantly, opportunistic infections with other lymphotrophic herpes
      viruses such as Epstein-Barr virus and human herpesvirus 8. Histologically
      lymphomas fall into three groups: (1) those also occurring in immunocompetent
      patients; (2) those occurring more specifically in HIV-positive patients; and (3)
      those also occurring in patients with other forms of immunosuppression.
      Aggressive lymphomas account for the vast majority cases. They frequently present
      with advanced stage, bulky disease with high tumour burden and, typically,
      involve extranodal sites. Clinical outcome appears to be worse than in similar
      aggressive lymphomas in the general population. However, following the
      introduction of highly active antiretroviral therapy, the risk for developing
      lymphoma in the context of HIV infection has decreased and the clinical outcome
      has improved.

PMID- 18042693
TI  - Adult T-cell leukaemia/lymphoma.
AB  - Adult T-cell leukaemia/lymphoma (ATLL) is a mature T-cell neoplasm of post-thymic
      lymphocytes aetiologically linked to the human T-cell lymphotropic virus, HTLV-I,
      and with a distinct geographical distribution. The disease manifests with
      leukaemia in greater than two thirds of patients, while the remaining patients
      have a lymphomatous form. According to the disease manifestations, various forms
      which differ in clinical course and prognosis have been recognised: acute,
      chronic, smouldering and lymphoma. Organomegaly, skin involvement, circulating
      atypical lymphocytes ("flower" cells) with a CD4+ CD25+ phenotype and
      hypercalcaemia are the most common disease features. The diagnosis should be
      based on a constellation of clinical features and laboratory investigations. The
      latter comprise: lymphocyte morphology, immunophenotype, histology of the tissues
      affected in the pure lymphoma forms and serology or DNA analysis for HTLV-I. The
      differential diagnosis of ATLL includes other mature T-cell neoplasms such as T
      cell prolymphocytic leukaemia (T-PLL), Sezary syndrome (SS), peripheral T-cell
      lymphomas and occasionally healthy carriers of the virus or Hodgkin disease. The
      clinical course is aggressive with a median survival of less than 12 months in
      the acute and lymphoma forms. Despite major advances in understanding the
      pathogenesis of the disease, management of these patients remains a challenge for
      clinicians as they do not respond or achieve only transient responses to
      therapies used in high-grade lymphomas. The use of antiretroviral agents such as
      zidovudine in combination with interferon-alpha, with or without concomitant
      chemotherapy, has shown activity in this disease with improvement in survival and
      response rate. Consolidation with high dose therapy and autologous or allogeneic
      stem-cell transplantation should be considered in young patients.

PMID- 18042694
TI  - Hepatitis C virus and lymphoma.
AB  - Hepatitis C virus (HCV) is well known for its aetiological role in chronic non-A,
      non-B viral hepatitis, liver cirrhosis and hepatocellular carcinoma; in addition,
      the virus has also been implicated in a number of extra-hepatic "autoimmune"
      disease manifestations. A causative association between HCV and non-Hodgkin
      lymphoma (NHL) was postulated relatively recently and has been the subject of
      intense investigation, as well as some debate. On the strength of epidemiological
      data, emerging biological investigations and clinical observations, HCV appears
      to be involved in the pathogenesis of at least a proportion of patients with NHL.
      Morphologically, HCV-associated lymphomas represent a variety of histological
      subtypes including marginal zone lymphoma (splenic, nodal and extranodal), small
      lymphocytic lymphoma/chronic lymphocytic leukaemia, lymphoplasmacytic lymphoma
      and diffuse large B-cell lymphoma. Remarkably, some HCV-associated NHL appears to
      be highly responsive to antiviral therapy, providing some clinical evidence for
      this relationship, as well as the prospect for novel therapeutic intervention.

PMID- 18042695
TI  - Molecular aspects of HTLV-I infection and adult T-cell leukaemia/lymphoma.
AB  - Human T-cell lymphotropic virus-I (HTLV-I) is the cause of adult T-cell
      leukaemia/lymphoma. Various viral proteins, especially, but not exclusively, Tax
      have been implicated in oncogenesis, mostly through in vitro studies. Tax
      transactivates a large and apparently ever expanding list of human genes through
      transcriptional factors. Elucidating not only the pathways but also the timing of
      action of HTLV proteins is important for understanding the pathogenesis and
      development of new treatments.

PMID- 18042697
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 18042696
TI  - Epstein-Barr virus and Burkitt lymphoma.
AB  - Burkitt lymphoma (BL) is an aggressive B-cell malignancy with endemic, sporadic
      and immunodeficiency-associated variants. It has been known for many years that
      the fundamental transforming event in BL is the translocation of the MYC gene,
      and the events that bring about this translocation and those that allow cells to
      survive with the constitutive expression of MYC have been the subject of intense
      investigation. Epstein-Barr virus (EBV) infection, malaria, immunodeficiency and
      spontaneous, somatic mutation can all contribute to the origin and maintenance of
      this cancer and their mechanisms are the subject of this review.

PMID- 18042698
TI  - Blocking LIF action in the uterus by using a PEGylated antagonist prevents
      implantation: a nonhormonal contraceptive strategy.
AB  - Blastocyst implantation is a critical stage in the establishment of pregnancy.
      Leukemia inhibitory factor (LIF) is essential for mouse blastocyst implantation
      and also plays a role in human pregnancy. We examined the effect of a potent LIF
      antagonist (LA) on mouse implantation. In mice, LIF expression peaks on day 3.5
      of pregnancy (D3.5) (D0.5 = day of mating plug detection) in the uterine
      glandular epithelium. LA (7 mg/kg per day) administered from D2.5 to D4.5 via
      four hourly i.p. injections plus continuous administration via miniosmotic pump
      resulted in complete implantation failure. To improve its pharmacokinetic
      properties, we conjugated LA to polyethylene glycol (PEG), achieving a
      significant increase in serum levels. PEGylated LA (PEGLA) (37.5 mg/kg per day)
      administered via three i.p. injections between D2.5 and D3.5 also resulted in
      complete implantation failure. PEGLA immunolocalized to the uterine luminal
      epithelium at the time of blastocyst implantation. Both LA and PEGLA reduced
      phosphorylation of the downstream signaling molecule STAT3 in luminal epithelial
      cells on D3.5. The effects of PEGLA were found to be endometrial, with no embryo
      lethal effects observed. These data demonstrate that administration of a
      PEGylated LIF antagonist is an effective method of targeting LIF signaling in the
      endometrium and a promising novel approach in the development of nonhormonal
      contraceptives for women.

PMID- 18042699
TI  - Evolutionary plasticity of developmental gene regulatory network architecture.
AB  - Sea stars and sea urchins evolved from a last common ancestor that lived at the
      end of the Cambrian, approximately half a billion years ago. In a previous
      comparative study of the gene regulatory networks (GRNs) that embody the genomic
      program for embryogenesis in these animals, we discovered an almost perfectly
      conserved five-gene network subcircuit required for endoderm specification. We
      show here that the GRN structure upstream and downstream of the conserved network
      kernel has, by contrast, diverged extensively. Mesoderm specification is
      accomplished quite differently; the Delta-Notch signaling system is used in
      radically distinct ways; and various regulatory genes have been coopted to
      different functions. The conservation of the conserved kernel is thus the more
      remarkable. The results indicate types of network linkage subject to evolutionary
      change. An emergent theme is that subcircuit design may be preserved even while
      the identity of genes performing given roles changes because of alteration in
      their cis-regulatory control systems.

PMID- 18042700
TI  - A biochemical approach to identifying microRNA targets.
AB  - Identifying the downstream targets of microRNAs (miRNAs) is essential to
      understanding cellular regulatory networks. We devised a direct biochemical
      method for miRNA target discovery that combined RNA-induced silencing complex
      (RISC) purification with microarray analysis of bound mRNAs. Because targets of
      miR-124a have been analyzed, we chose it as our model. We honed our approach both
      by examining the determinants of stable binding between RISC and synthetic target
      RNAs in vitro and by determining the dependency of both repression and RISC
      coimmunoprecipitation on miR-124a seed sites in two of its well characterized
      targets in vivo. Examining the complete spectrum of miR-124 targets in 293 cells
      yielded both a set that were down-regulated at the mRNA level, as previously
      observed, and a set whose mRNA levels were unaffected by miR-124a. Reporter
      assays validated both classes, extending the spectrum of mRNA targets that can be
      experimentally linked to the miRNA pathway.

PMID- 18042701
TI  - Cryo-EM study of the spinach chloroplast ribosome reveals the structural and
      functional roles of plastid-specific ribosomal proteins.
AB  - Protein synthesis in the chloroplast is carried out by chloroplast ribosomes
      (chloro-ribosome) and regulated in a light-dependent manner. Chloroplast or
      plastid ribosomal proteins (PRPs) generally are larger than their bacterial
      counterparts, and chloro-ribosomes contain additional plastid-specific ribosomal
      proteins (PSRPs); however, it is unclear to what extent these proteins play
      structural or regulatory roles during translation. We have obtained a three
      dimensional cryo-EM map of the spinach 70S chloro-ribosome, revealing the overall
      structural organization to be similar to bacterial ribosomes. Fitting of the
      conserved portions of the x-ray crystallographic structure of the bacterial 70S
      ribosome into our cryo-EM map of the chloro-ribosome reveals the positions of PRP
      extensions and the locations of the PSRPs. Surprisingly, PSRP1 binds in the
      decoding region of the small (30S) ribosomal subunit, in a manner that would
      preclude the binding of messenger and transfer RNAs to the ribosome, suggesting
      that PSRP1 is a translation factor rather than a ribosomal protein. PSRP2 and
      PSRP3 appear to structurally compensate for missing segments of the 16S rRNA
      within the 30S subunit, whereas PSRP4 occupies a position buried within the head
      of the 30S subunit. One of the two PSRPs in the large (50S) ribosomal subunit
      lies near the tRNA exit site. Furthermore, we find a mass of density
      corresponding to chloro-ribosome recycling factor; domain II of this factor
      appears to interact with the flexible C-terminal domain of PSRP1. Our study
      provides evolutionary insights into the structural and functional roles that the
      PSRPs play during protein synthesis in chloroplasts.

PMID- 18042702
TI  - Specific subgroups of FruM neurons control sexually dimorphic patterns of
      aggression in Drosophila melanogaster.
AB  - A great challenge facing neuroscience is to understand how genes, molecules,
      cells, circuits, and systems interact to generate social behavior. Fruit flies
      (Drosophila melanogaster) offer a powerful model system to address questions of
      this magnitude. These animals display genetically specified, sexually dimorphic
      patterns of fighting behavior via sex-specific splicing of the fruitless gene.
      Here, we show that sexually dimorphic behavioral patterns displayed during
      aggression are controlled by specific subgroups of neurons expressing male forms
      of fruitless proteins (Fru(M)). Using the GAL4/UAS system to manipulate
      transformer expression, we feminized or masculinized different populations of
      neurons in fly nervous systems. With a panneuronal elav-GAL4 driver, male
      patterns of fighting behavior were transferred into females and female patterns
      into males. We screened 60 Gal4 lines that express the yeast transcription factor
      in different patterns in fly central nervous systems and found five that showed
      abnormal same-sex courtship behavior. The sexually dimorphic fighting patterns,
      however, were completely switched only in one and partially switched in a second
      of these lines. In the other three lines, female patterns of aggression were seen
      despite a switch in courtship preference. A tight correspondence was seen between
      Fru(M) expression and how flies fight in several subgroups of neurons usually
      expressing these proteins: Expression is absent when flies fight like females and
      present when flies fight like males, thereby beginning a separation between
      courtship and aggression among these neurons.

PMID- 18042704
TI  - Extensive simple sequence repeat genotyping of potato landraces supports a major
      reevaluation of their gene pool structure and classification.
AB  - Contrasting taxonomic treatments of potato landraces have continued over the last
      century, with the recognition of anywhere from 1 to 21 distinct Linnean species,
      or of Cultivar Groups within the single species Solanum tuberosum. We provide one
      of the largest molecular marker studies of any crop landraces to date, to include
      an extensive study of 742 landraces of all cultivated species (or Cultivar
      Groups) and 8 closely related wild species progenitors, with 50 nuclear simple
      sequence repeat (SSR) (also known as microsatellite) primer pairs and a plastid
      DNA deletion marker that distinguishes most lowland Chilean from upland Andean
      landraces. Neighbor-joining results highlight a tendency to separate three
      groups: (i) putative diploids, (ii) putative tetraploids, and (iii) the hybrid
      cultivated species S. ajanhuiri (diploid), S. juzepczukii (triploid), and S.
      curtilobum (pentaploid). However, there are many exceptions to grouping by
      ploidy. Strong statistical support occurs only for S. ajanhuiri, S. juzepczukii,
      and S. curtilobum. In combination with recent morphological analyses and an
      examination of the identification history of these collections, we support the
      reclassification of the cultivated potatoes into four species: (i) S. tuberosum,
      with two Cultivar Groups (Andigenum Group of upland Andean genotypes containing
      diploids, triploids, and tetraploids, and the Chilotanum Group of lowland
      tetraploid Chilean landraces); (ii) S. ajanhuiri (diploid); (iii) S. juzepczukii
      (triploid); and (iv) S. curtilobum (pentaploid). For other classifications,
      consistent and stable identifications are impossible, and their classification as
      species is artificial and only maintains the confusion of users of the gene banks
      and literature.

PMID- 18042703
TI  - B7-H3 and B7x are highly expressed in human prostate cancer and associated with
      disease spread and poor outcome.
AB  - B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to
      dampen peripheral immune responses via negative costimulation. We evaluated their
      potential expression in human prostate cancer using a large cohort of patients
      with 7 years of follow-up. We identified 823 patients with tissue available
      treated with radical prostatectomy between 1985 and 2003. Immunohistochemistry
      was performed on tissue microarray sections using anti-B7-H3 and -B7x. The
      percentage and intensity of immunoreactivity by tumor cells were blindly
      evaluated by two urological pathologists, and outcome analyses were conducted.
      Both B7-H3 and B7x were highly expressed; 93% and 99% of tumors had aberrant
      expression, respectively. The median percentage of tumor cells staining positive
      was 80% for each molecule. Strong intensity for B7-H3 and B7x was noted in 212
      (26%) and 120 (15%) patients, respectively. Patients with strong intensity for B7
      H3 and B7x were significantly more likely to have disease spread at time of
      surgery (P < 0.001 and P = 0.005, respectively). Additionally, patients with
      strong intensity for B7-H3 and B7x were at significantly increased risk of
      clinical cancer recurrence (P < 0.001 and P = 0.005) and cancer-specific death (P
      = 0.004 and P = 0.04, respectively). To our knowledge, we present the largest
      investigation of B7 family molecules in a human malignancy and a previously
      undescribed evaluation of B7x in prostate cancer. B7-H3 and B7x are abundantly
      expressed in prostate cancer and associated with disease spread and poor outcome.
      Given the proposed immune-inhibitory mechanisms of B7-H3 and B7x, these molecules
      represent attractive targets for therapeutic manipulation in prostate cancer.

PMID- 18042705
TI  - Disulfide bond influence on protein structural dynamics probed with 2D-IR
      vibrational echo spectroscopy.
AB  - Intramolecular disulfide bonds are understood to play a role in regulating
      protein stability and activity. Because disulfide bonds covalently link different
      components of a protein, they influence protein structure. However, the effects
      of disulfide bonds on fast (subpicosecond to approximately 100 ps) protein
      equilibrium structural fluctuations have not been characterized experimentally.
      Here, ultrafast 2D-IR vibrational echo spectroscopy is used to examine the
      constraints an intramolecular disulfide bond places on the structural
      fluctuations of the protein neuroglobin (Ngb). Ngb is a globin family protein
      found in vertebrate brains that binds oxygen reversibly. Like myoglobin (Mb), Ngb
      has the classical globin fold and key residues around the heme are conserved.
      Furthermore, the heme-ligated CO vibrational spectra of Mb (Mb-CO) and Ngb (Ngb
      CO) are virtually identical. However, in contrast to Mb, human Ngb has an
      intramolecular disulfide bond that affects its oxygen affinity and protein
      stability. By using 2D-IR vibrational echo spectroscopy, we investigated the
      equilibrium protein dynamics of Ngb-CO by observing the CO spectral diffusion
      (time dependence of the 2D-IR line shapes) with and without the disulfide bond.
      Despite the similarity of the linear FTIR spectra of Ngb-CO with and without the
      disulfide bond, 2D-IR measurements reveal that the equilibrium sampling of
      different protein configurations is accelerated by disruption of the disulfide
      bond. The observations indicate that the intramolecular disulfide bond in Ngb
      acts as an inhibitor of fast protein dynamics even though eliminating it does not
      produce significant conformational change in the protein's structure.

PMID- 18042707
TI  - The discovery of kelp forests in deep-water habitats of tropical regions.

PMID- 18042706
TI  - Structural differentiation of skeletal muscle fibers in the absence of
      innervation in humans.
AB  - The relative importance of muscle activity versus neurotrophic factors in the
      maintenance of muscle differentiation has been greatly debated. Muscle biopsies
      from spinal cord injury patients, who were trained with an innovative protocol of
      functional electrical stimulation (FES) for prolonged periods (2.4-9.3 years),
      offered the unique opportunity of studying the structural recovery of denervated
      fibers from severe atrophy under the sole influence of muscle activity. FES
      stimulation induced surprising recovery of muscle structure, mass, and force even
      in patients whose muscles had been denervated for prolonged periods before the
      beginning of FES training (up to 2 years) and had almost completely lost muscle
      specific internal organization. Ninety percent (or more) of the fibers analyzed
      by electron microscopy showed a striking recovery of the ultrastructural
      organization of myofibrils and Ca(2+)-handling membrane systems. This
      functional/structural restoration follows a pattern that mimics some aspects of
      normal muscle differentiation. Most importantly, the recovery occurs in the
      complete absence of motor and sensory innervation and of nerve-derived trophic
      factors, that is, solely under the influence of muscle activity induced by
      electrical stimulation.

PMID- 18042708
TI  - The P2 capsid protein of the nonenveloped rice dwarf phytoreovirus induces
      membrane fusion in insect host cells.
AB  - Insect transmission is an essential process of infection for numerous plant and
      animal viruses. How an insect-transmissible plant virus enters an insect cell to
      initiate the infection cycle is poorly understood, especially for nonenveloped
      plant and animal viruses. The capsid protein P2 of rice dwarf virus (RDV), which
      is nonenveloped, is necessary for insect transmission. Here, we present evidence
      that P2 shares structural features with membrane-fusogenic proteins encoded by
      enveloped animal viruses. When RDV P2 was ectopically expressed and displayed on
      the surface of insect Spodoptera frugiperda cells, it induced membrane fusion
      characterized by syncytium formation at low pH. Mutational analyses identified
      the N-terminal and a heptad repeat as being critical for the membrane fusion
      inducing activity. These results are corroborated with results from RDV-infected
      cells of the insect vector leafhopper. We propose that the RDV P2-induced
      membrane fusion plays a critical role in viral entry into insect cells. Our
      report that a plant viral protein can induce membrane fusion has broad
      significance in studying the mechanisms of virus entry into insect cells and
      insect transmission of nonenveloped plant and animal viruses.

PMID- 18042709
TI  - Yeast gain-of-function mutations reveal structure-function relationships
      conserved among different subfamilies of transient receptor potential channels.
AB  - Transient receptor potential (TRP) channels found in animals, protists, and fungi
      are primary chemo-, thermo-, or mechanosensors. Current research emphasizes the
      characteristics of individual channels in each animal TRP subfamily but not the
      mechanisms common across subfamilies. A forward genetic screen of the TrpY1, the
      yeast TRP channel, recovered gain-of-function (GOF) mutations with phenotype in
      vivo and in vitro. Single-channel patch-clamp analyses of these GOF-mutant
      channels show prominent aberrations in open probability and channel kinetics.
      These mutations revealed functionally important aromatic amino acid residues in
      four locations: at the intracellular end of the fifth transmembrane helix (TM5),
      at both ends of TM6, and at the immediate extension of TM6. These aromatics have
      counterparts in most TRP subfamilies. The one in TM5 (F380L) aligns precisely
      with an exceptional Drosophila mutant allele (F550I) that causes constitutive
      activity in the canonical TRP channel, resulting in rapid and severe retinal
      degeneration beyond mere loss of phototaxis. Thus, this phenylalanine maintains
      the balance of various functional states (conformations) of a channel for insect
      phototransduction as well as one for fungal mechanotransduction. This residue is
      among a small cluster of phenylalanines found in all known subfamilies of TRP
      channels. This unique case illustrates that GOF mutations can reveal structure
      function principles that can be generalized across different TRP subfamilies. It
      appears that the conserved aromatics in the four locations have conserved
      functions in most TRP channels. The possible mechanistic roles of these aromatics
      and the further use of yeast genetics to dissect TRP channels are discussed.

PMID- 18042710
TI  - In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence
      lifetimes, and cellular morphology in precancerous epithelia.
AB  - Metabolic imaging of the relative amounts of reduced NADH and FAD and the
      microenvironment of these metabolic electron carriers can be used to
      noninvasively monitor changes in metabolism, which is one of the hallmarks of
      carcinogenesis. This study combines cellular redox ratio, NADH and FAD lifetime,
      and subcellular morphology imaging in three dimensions to identify intrinsic
      sources of metabolic and structural contrast in vivo at the earliest stages of
      cancer development. There was a significant (P < 0.05) increase in the nuclear to
      cytoplasmic ratio (NCR) with depth within the epithelium in normal tissues;
      however, there was no significant change in NCR with depth in precancerous
      tissues. The redox ratio significantly decreased in the less differentiated basal
      epithelial cells compared with the more mature cells in the superficial layer of
      the normal stratified squamous epithelium, indicating an increase in metabolic
      activity in cells with increased NCR. However, the redox ratio was not
      significantly different between the superficial and basal cells in precancerous
      tissues. A significant decrease was observed in the contribution and lifetime of
      protein-bound NADH (averaged over the entire epithelium) in both low- and high
      grade epithelial precancers compared with normal epithelial tissues. In addition,
      a significant increase in the protein-bound FAD lifetime and a decrease in the
      contribution of protein-bound FAD are observed in high-grade precancers only.
      Increased intracellular variability in the redox ratio, NADH, and FAD
      fluorescence lifetimes were observed in precancerous cells compared with normal
      cells.

PMID- 18042711
TI  - Tumor cell-selective regulation of NOXA by c-MYC in response to proteasome
      inhibition.
AB  - The proteasome controls a plethora of survival factors in all mammalian cells
      analyzed to date. Therefore, it is puzzling that proteasome inhibitors such as
      bortezomib can display a preferential toxicity toward malignant cells. In fact,
      proteasome inhibitors have the salient feature of promoting a dramatic induction
      of the proapoptotic protein NOXA in a tumor cell-restricted manner. However, the
      molecular determinants that control this specific regulation of NOXA are unknown.
      Here, we show that the induction of NOXA by bortezomib is directly dependent on
      the oncogene c-MYC. This requirement for c-MYC was found in a variety of tumor
      cell types, in marked contrast with dispensable roles of p53, HIF-1alpha, and E2F
      1 (classical proteasomal targets that can regulate NOXA mRNA under stress).
      Conserved MYC-binding sites identified at the NOXA promoter were validated by
      ChIP and reporter assays. Down-regulation of the endogenous levels of c-MYC
      abrogated the induction of NOXA in proteasome-defective tumor cells. Conversely,
      forced expression of c-MYC enabled normal cells to accumulate NOXA and
      subsequently activate cell death programs in response to proteasome blockage. c
      MYC is itself a proteasomal target whose levels or function are invariably up
      regulated during tumor progression. Our data provide an unexpected function of c
      MYC in the control of the apoptotic machinery, and reveal a long sought-after
      oncogenic event conferring sensitivity to proteasome inhibition.

PMID- 18042712
TI  - Genetic variation in the cysteine biosynthesis pathway causes sensitivity to
      pharmacological compounds.
AB  - Complex traits are the product of multiple genes with effects that depend on both
      the genetic and environmental background. Although this complexity makes a
      comprehensive genetic analysis difficult, identification of even a single gene
      provides insight into the biochemical and/or signaling pathway underlying a
      trait. However, it is unknown whether multiple pathways, and consequently
      multiple genes, must be identified to adequately understand a trait's molecular
      basis. Using crosses between three natural isolates of Saccharomyces cerevisiae,
      we mapped sensitivity to a number of pharmacologically active compounds to a
      single nonsynonymous polymorphism in cystathione-beta-synthase (CYS4), which is
      required for the first committed step in the cysteine biosynthesis pathway. Drug
      sensitivity is mediated by a deficiency in cysteine and consequently glutathione
      production, because drug sensitivity is abrogated by cysteine or glutathione
      supplementation. Within a diverse panel of 60 natural yeast isolates, the drug
      sensitive CYS4 allele is rare, and glutathione supplementation failed to
      alleviate drug-dependent growth defects in two other drug-sensitive strains.
      These results implicate the cysteine/glutathione biosynthesis pathway as a
      significant, but not the sole contributor to pharmacological variation in yeast.

PMID- 18042713
TI  - A dual function for a bacterial small RNA: SgrS performs base pairing-dependent
      regulation and encodes a functional polypeptide.
AB  - SgrS is a 227-nt small RNA that is expressed in Escherichia coli during glucose
      phosphate stress, a condition associated with intracellular accumulation of
      glucose-6-phosphate caused by disruption of glycolytic flux. Under stress
      conditions, SgrS negatively regulates translation and stability of the ptsG mRNA,
      encoding the major glucose transporter, by means of a base pairing-dependent
      mechanism requiring the RNA chaperone Hfq. SgrS activity mitigates the effects of
      glucose-phosphate stress, and the present study has elucidated a function of SgrS
      that is proposed to contribute to the stress response. The 5' end of SgrS,
      upstream of the nucleotides involved in base pairing with the ptsG mRNA, contains
      a 43-aa ORF, sgrT, that is conserved in most species that contain SgrS-like small
      RNAs. The sgrT gene is translated in E. coli under conditions of glucose
      phosphate stress. Analysis of alleles that separate the base pairing function of
      SgrS from the sgrT coding sequence revealed that either of these functions alone
      are sufficient for previously characterized SgrS phenotypes. SgrS-dependent down
      regulation of ptsG mRNA stability does not require SgrT and SgrT by itself has no
      effect on ptsG mRNA stability. Cells expressing sgrT alone had a defect in
      glucose uptake even though they had nearly wild-type levels of PtsG (IICB(Glc)).
      Together, these data suggest that SgrS represents a previously unrecognized
      paradigm for small RNA (sRNA) regulators as a bifunctional RNA that encodes
      physiologically redundant but mechanistically distinct functions contributing to
      the same stress response.

PMID- 18042714
TI  - HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous
      recombination.
AB  - Histone deacetylase (HDAC) inhibitors such as the phenyl hydroxamic acid PCI
      24781 have emerged recently as a class of therapeutic agents for the treatment of
      cancer. Recent data showing synergy of HDAC inhibitors with ionizing radiation
      and other DNA-damaging agents have suggested that HDAC inhibitors may act, in
      part, by inhibiting DNA repair. Here we present evidence that HDAC enzymes are
      important for homologous recombinational repair of DNA double-strand breaks.
      Combination studies of PCI-24781 with the poly(ADP-ribose) polymerase inhibitor
      PJ34, an agent thought to produce lesions repaired by homologous recombination
      (HR), resulted in a synergistic effect on apoptosis. Immunofluorescence analysis
      demonstrated that HDAC inhibition caused a complete inhibition of subnuclear
      repair foci in response to ionizing radiation. Mechanistic investigations
      revealed that inhibition of HDAC enzymes by PCI-24781 led to a significant
      reduction in the transcription of genes specifically associated with HR,
      including RAD51. RAD51 protein levels were significantly decreased after 24 h of
      drug exposure both in vitro and in vivo. Consistent with inhibition of HR,
      treatment with PCI-24781 resulted in a decreased ability to perform homology
      directed repair of I-SceI-induced chromosome breaks in transfected CHO cells. In
      addition, an enhancement of cell killing was observed in Ku mutant cells lacking
      functional nonhomologous end joining compared with WT cells. Together these
      results demonstrate that HDAC enzymes are critically important to enable
      functional HR by controlling the expression of HR-related genes and promoting the
      proper assembly of HR-directed subnuclear foci.

PMID- 18042715
TI  - Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range
      interaction with active genes.
AB  - Mutations in MECP2 cause the autism-spectrum disorder Rett syndrome. MeCP2 is
      predicted to bind to methylated promoters and silence transcription. However, the
      first large-scale mapping of neuronal MeCP2-binding sites on 26.3 Mb of imprinted
      and nonimprinted loci revealed that 59% of MeCP2-binding sites are outside of
      genes and that only 6% are in CpG islands. Integrated genome-wide promoter
      analysis of MeCP2 binding, CpG methylation, and gene expression revealed that 63%
      of MeCP2-bound promoters are actively expressed and that only 6% are highly
      methylated. These results indicate that the primary function of MeCP2 is not the
      silencing of methylated promoters.

PMID- 18042716
TI  - The blinking spotlight of attention.
AB  - Increasing evidence suggests that attention can concurrently select multiple
      locations; yet it is not clear whether this ability relies on continuous
      allocation of attention to the different targets (a "parallel" strategy) or
      whether attention switches rapidly between the targets (a periodic "sampling"
      strategy). Here, we propose a method to distinguish between these two
      alternatives. The human psychometric function for detection of a single target as
      a function of its duration can be used to predict the corresponding function for
      two or more attended targets. Importantly, the predicted curves differ, depending
      on whether a parallel or sampling strategy is assumed. For a challenging
      detection task, we found that human performance was best reflected by a sampling
      model, indicating that multiple items of interest were processed in series at a
      rate of approximately seven items per second. Surprisingly, the data suggested
      that attention operated in this periodic regime, even when it was focused on a
      single target. That is, attention might rely on an intrinsically periodic
      process.

PMID- 18042717
TI  - DNA methylation, insulin resistance, and blood pressure in offspring determined
      by maternal periconceptional B vitamin and methionine status.
AB  - A complex combination of adult health-related disorders can originate from
      developmental events that occur in utero. The periconceptional period may also be
      programmable. We report on the effects of restricting the supply of specific B
      vitamins (i.e., B(12) and folate) and methionine, within normal physiological
      ranges, from the periconceptional diet of mature female sheep. We hypothesized
      this would lead to epigenetic modifications to DNA methylation in the
      preovulatory oocyte and/or preimplantation embryo, with long-term health
      implications for offspring. DNA methylation is a key epigenetic contributor to
      maintenance of gene silencing that relies on a dietary supply of methyl groups.
      We observed no effects on pregnancy establishment or birth weight, but this
      modest early dietary intervention led to adult offspring that were both heavier
      and fatter, elicited altered immune responses to antigenic challenge, were
      insulin-resistant, and had elevated blood pressure-effects that were most obvious
      in males. The altered methylation status of 4% of 1,400 CpG islands examined by
      restriction landmark genome scanning in the fetal liver revealed compelling
      evidence of a widespread epigenetic mechanism associated with this nutritionally
      programmed effect. Intriguingly, more than half of the affected loci were
      specific to males. The data provide the first evidence that clinically relevant
      reductions in specific dietary inputs to the methionine/folate cycles during the
      periconceptional period can lead to widespread epigenetic alterations to DNA
      methylation in offspring, and modify adult health-related phenotypes.

PMID- 18042718
TI  - Protein protein interaction inhibition (2P2I) combining high throughput and
      virtual screening: Application to the HIV-1 Nef protein.
AB  - Protein-protein recognition is the cornerstone of multiple cellular and
      pathological functions. Therefore, protein-protein interaction inhibition (2P2I)
      is endowed with great therapeutic potential despite the initial belief that 2P2I
      was refractory to small-molecule intervention. Improved knowledge of complex
      molecular binding surfaces has recently stimulated renewed interest for 2P2I,
      especially after identification of "hot spots" and first inhibitory compounds.
      However, the combination of target complexity and lack of starting compound has
      thwarted experimental results and created intellectual barriers. Here we combined
      virtual and experimental screening when no previously known inhibitors can be
      used as starting point in a structure-based research program that targets an SH3
      binding surface of the HIV type I Nef protein. High-throughput docking and
      application of a pharmacophoric filter on one hand and search for analogy on the
      other hand identified drug-like compounds that were further confirmed to bind Nef
      in the micromolar range (isothermal titration calorimetry), to target the Nef SH3
      binding surface (NMR experiments), and to efficiently compete for Nef-SH3
      interactions (cell-based assay, GST pull-down). Initial identification of these
      compounds by virtual screening was validated by screening of the very same
      library of compounds in the cell-based assay, demonstrating that a significant
      enrichment factor was attained by the in silico screening. To our knowledge, our
      results identify the first set of drug-like compounds that functionally target
      the HIV-1 Nef SH3 binding surface and provide the basis for a powerful discovery
      process that should help to speed up 2P2I strategies and open avenues for new
      class of antiviral molecules.

PMID- 18042719
TI  - CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human
      monocytes/macrophages.
AB  - CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are potent suppressors of the
      adaptive immune system, but their effects on innate immune cells are less well
      known. Here we demonstrate a previously uncharacterized function of Tregs, namely
      their ability to steer monocyte differentiation toward alternatively activated
      macrophages (AAM). AAM are cells with strong antiinflammatory potential involved
      in immune regulation, tissue remodeling, parasite killing, and tumor promotion.
      We show that, after coculture with Tregs, monocytes/macrophages display typical
      features of AAM, including up-regulated expression of CD206 (macrophage mannose
      receptor) and CD163 (hemoglobin scavenger receptor), an increased production of
      CCL18, and an enhanced phagocytic capacity. In addition, the
      monocytes/macrophages have reduced expression of HLA-DR and a strongly reduced
      capacity to respond to LPS in terms of proinflammatory mediator production (IL
      1beta, IL-6, IL-8, MIP-1alpha, TNF-alpha), NFkappaB activation, and tyrosine
      phosphorylation. Mechanistic studies reveal that CD4(+)CD25(+)CD127(low)Foxp3(+)
      Tregs produce IL-10, IL-4, and IL-13 and that these cytokines are the critical
      factors involved in the suppression of the proinflammatory cytokine response. In
      contrast, the Treg-mediated induction of CD206 is entirely cytokine-independent,
      whereas the up-regulation of CD163, CCL18, and phagocytosis are (partly)
      dependent on IL-10 but not on IL-4/IL-13. Together these data demonstrate a
      previously unrecognized function of CD4(+)CD25(+)Foxp3(+) Tregs, namely their
      ability to induce alternative activation of monocytes/macrophages. Moreover, the
      data suggest that the Treg-mediated induction of AAM partly involves a novel,
      cytokine-independent pathway.

PMID- 18042720
TI  - Silencing of OB-RGRP in mouse hypothalamic arcuate nucleus increases leptin
      receptor signaling and prevents diet-induced obesity.
AB  - Obesity is a major public health problem and is often associated with type 2
      diabetes mellitus, cardiovascular disease, and metabolic syndrome. Leptin is the
      crucial adipostatic hormone that controls food intake and body weight through the
      activation of specific leptin receptors (OB-R) in the hypothalamic arcuate
      nucleus (ARC). However, in most obese patients, high circulating levels of leptin
      fail to bring about weight loss. The prevention of this "leptin resistance" is a
      major goal for obesity research. We report here a successful prevention of diet
      induced obesity (DIO) by silencing a negative regulator of OB-R function, the OB
      R gene-related protein (OB-RGRP), whose transcript is genetically linked to the
      OB-R transcript. We provide in vitro evidence that OB-RGRP controls OB-R function
      by negatively regulating its cell surface expression. In the DIO mouse model,
      obesity was prevented by silencing OB-RGRP through stereotactic injection of a
      lentiviral vector encoding a shRNA directed against OB-RGRP in the ARC. This work
      demonstrates that OB-RGRP is a potential target for obesity treatment. Indeed,
      regulators of the receptor could be more appropriate targets than the receptor
      itself. This finding could serve as the basis for an approach to identifying
      potential new therapeutic targets for a variety of diseases, including obesity.

PMID- 18042721
TI  - Modulation of metabolic brain networks after subthalamic gene therapy for
      Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by elevated expression of an abnormal
      metabolic brain network that is reduced by clinically effective treatment. We
      used fluorodeoxyglucose (FDG) positron emission tomography (PET) to determine the
      basis for motor improvement in 12 PD patients receiving unilateral subthalamic
      nucleus (STN) infusion of an adenoassociated virus vector expressing glutamic
      acid decarboxylase (AAV-GAD). After gene therapy, we observed significant
      reductions in thalamic metabolism on the operated side as well as concurrent
      metabolic increases in ipsilateral motor and premotor cortical regions. Abnormal
      elevations in the activity of metabolic networks associated with motor and
      cognitive functioning in PD patients were evident at baseline. The activity of
      the motor-related network declined after surgery and persisted at 1 year. These
      network changes correlated with improved clinical disability ratings. By
      contrast, the activity of the cognition-related network did not change after gene
      transfer. This suggests that modulation of abnormal network activity underlies
      the clinical outcome observed after unilateral STN AAV-GAD gene therapy. Network
      biomarkers may be used as physiological assays in early-phase trials of
      experimental therapies for PD and other neurodegenerative disease.

PMID- 18042722
TI  - Matrix metalloproteinase 7 controls pancreatic acinar cell transdifferentiation
      by activating the Notch signaling pathway.
AB  - Acinar-to-ductal metaplasia in the pancreas is associated with an increased risk
      for tumorigenesis. Molecular dissection of this process in vitro has shown that
      primary acinar cells, in response to EGF receptor ligands, can transdifferentiate
      into duct-like epithelia, passing through a nestin-positive intermediate, in a
      Notch pathway-dependent manner. Here, we show that in vitro acinar
      transdifferentiation depends on matrix metalloproteinase 7 (MMP-7), a proteinase
      expressed in most metaplastic epithelia in vivo. MMP-7 was found to be required
      for Notch activation, which leads to dedifferentiation of acinar cells to the
      nestin-positive transitional cell. Besides being necessary for acinar
      transdifferentiation, it was found that MMP-7 activity was sufficient to induce
      the process, indicating that molecular signals capable of initiating MMP-7
      expression also have the potential to induce formation of metaplastic epithelia
      in the pancreas.

PMID- 18042723
TI  - Subnetwork analysis reveals dynamic features of complex (bio)chemical networks.
AB  - In analyzing and mathematical modeling of complex (bio)chemical reaction
      networks, formal methods that connect network structure and dynamic behavior are
      needed because often, quantitative knowledge of the networks is very limited.
      This applies to many important processes in cell biology. Chemical reaction
      network theory allows for the classification of the potential network behavior
      for instance, with respect to the existence of multiple steady states-but is
      computationally limited to small systems. Here, we show that by analyzing
      subnetworks termed elementary flux modes, the applicability of the theory can be
      extended to more complex networks. For an example network inspired by cell cycle
      control in budding yeast, the approach allows for model discrimination,
      identification of key mechanisms for multistationarity, and robustness analysis.
      The presented methods will be helpful in modeling and analyzing other complex
      reaction networks.

PMID- 18042724
TI  - CERK1, a LysM receptor kinase, is essential for chitin elicitor signaling in
      Arabidopsis.
AB  - Chitin is a major component of fungal cell walls and serves as a microbe
      associated molecular pattern (MAMP) for the detection of various potential
      pathogens in innate immune systems of both plants and animals. We recently showed
      that chitin elicitor-binding protein (CEBiP), plasma membrane glycoprotein with
      LysM motifs, functions as a cell surface receptor for chitin elicitor in rice.
      The predicted structure of CEBiP does not contain any intracellular domains,
      suggesting that an additional component(s) is required for signaling through the
      plasma membrane into the cytoplasm. Here, we identified a receptor-like kinase,
      designated CERK1, which is essential for chitin elicitor signaling in
      Arabidopsis. The KO mutants for CERK1 completely lost the ability to respond to
      the chitin elicitor, including MAPK activation, reactive oxygen species
      generation, and gene expression. Disease resistance of the KO mutant against an
      incompatible fungus, Alternaria brassicicola, was partly impaired.
      Complementation with the WT CERK1 gene showed cerk1 mutations were responsible
      for the mutant phenotypes. CERK1 is a plasma membrane protein containing three
      LysM motifs in the extracellular domain and an intracellular Ser/Thr kinase
      domain with autophosphorylation/myelin basic protein kinase activity, suggesting
      that CERK1 plays a critical role in fungal MAMP perception in plants.

PMID- 18042725
TI  - Histamine is stored in mast cells of most evolutionarily advanced fish and
      regulates the fish inflammatory response.
AB  - Mast cells are important as initiators and effectors of innate immunity and
      regulate the adaptive immune responses. They have been described in all classes
      of vertebrates and seem to be morphologically and functionally similar. However,
      early studies had shown that fish and amphibian mast cells were devoid of
      histamine. In this study, we take a fresh look at the evolution of histamine and
      find that the mast cells of fish belonging to the Perciformes order, the largest
      and most evolutionarily advanced order of teleosts, are armed with histamine.
      More importantly, histamine is biologically active in these fish where it is able
      to regulate the inflammatory response by acting on professional phagocytes. In
      addition, the actions of histamine in these immune cells seem to be mediated
      through the engagement of H(1) and H(2) receptors, which, together with the H(3)
      receptor, are well conserved in bony fish. We propose that the storage of
      histamine in vertebrate mast cells and its use as an inflammatory messenger was
      established in primitive reptiles (Lepidosauria) approximately 276 million years
      ago. This same feature seems to have developed independently in Perciform fish
      much more recently in the Lower Eocene, between 55 and 45 million years ago, a
      short period during which the great majority of Percomorph families appeared.

PMID- 18042726
TI  - Task-specific change of unconscious neural priming in the cerebral language
      network.
AB  - We explored the impact of task context on subliminal neural priming using
      functional magnetic resonance imaging. The repetition of words during semantic
      categorization produced activation reduction in the left middle temporal gyrus
      previously associated with semantic-level representation and dorsal premotor
      cortex. By contrast, reading aloud produced repetition enhancement in the left
      inferior parietal lobe associated with print-to-sound conversion and ventral
      premotor cortex. Analyses of effective connectivity revealed that the task set
      for reading generated reciprocal excitatory connections between the left inferior
      parietal and superior temporal regions, reflecting the audiovisual integration
      required for vocalization, whereas categorization did not produce such backward
      projection to posterior regions. Thus, masked repetition priming involves two
      distinct components in the task-specific neural streams, one in the
      parietotemporal cortex for task-specific word processing and the other in the
      premotor cortex for behavioral response preparation. The top-down influence of
      task sets further changes the directions of the unconscious priming in the entire
      cerebral circuitry for reading.

PMID- 18042727
TI  - Allograft rejection mediated by memory T cells is resistant to regulation.
AB  - Alloreactive memory T cells may be refractory to many of the tolerance-inducing
      strategies that are effective against naive T cells and thus present a
      significant barrier to long-term allograft survival. Because CD4(+)CD25(+)
      regulatory T cells (Tregs) are critical elements of many approaches to successful
      induction/maintenance of transplantation tolerance, we used MHC class I and II
      alloreactive TCR-transgenic models to explore the ability of antigen-specific
      Tregs to control antigen-specific memory T cell responses. Upon coadoptive
      transfer into RAG-1(-/-) mice, we found that Tregs effectively suppressed the
      ability of naive T cells to reject skin grafts, but neither antigen-unprimed nor
      antigen-primed Tregs suppressed rejection by memory T cells. Interestingly,
      different mechanisms appeared to be active in the ability of Tregs to control
      naive T cell-mediated graft rejection in the class II versus class I alloreactive
      models. In the former case, we observed decreased early expansion of effector
      cells in lymphoid tissue. In contrast, in the class I model, an effect of Tregs
      on early proliferation and expansion was not observed. However, at a late time
      point, significant differences in cell numbers were seen, suggesting effects on
      responding T cell survival. Overall, these data indicate that the relative
      resistance of both CD4(+) and CD8(+) alloreactive memory T cells to regulation
      may mediate resistance to tolerance induction seen in hosts with preexisting
      alloantigen-specific immunity and further indicate the multiplicity of mechanisms
      by which Tregs may control alloimmune responses in vivo.

PMID- 18042728
TI  - Cytoskeletal "jellyfish" structure of Mycoplasma mobile.
AB  - Mycoplasma mobile, a parasitic bacterium lacking a peptidoglycan layer, glides on
      solid surfaces in the direction of a membrane protrusion at a cell pole by a
      unique mechanism. Recently, we proposed a working model in which cells are
      propelled by leg proteins clustering at the protrusion's base. The legs
      repeatedly catch and release sialic acids on the solid surface, a motion that is
      driven by the force generated by ATP hydrolysis. Here, to clarify the subcellular
      structure supporting the gliding force and the cell shape, we stripped the
      membrane by Triton X-100 and identified a unique structure, designated the
      "jellyfish" structure. In this structure, an oval solid "bell" approximately 235
      wide and 155 nm long is filled with a 12-nm hexagonal lattice and connected to
      this structure are dozens of flexible "tentacles" that are covered with particles
      of 20-nm diameter at intervals of approximately 30 nm. The particles appear to
      have 180 degrees rotational symmetry and a dimple at the center. The relation of
      this structure to the gliding mechanism was suggested by its cellular
      localization and by analyses of mutants lacking proteins essential for gliding.
      We identified 10 proteins as the components by mass spectrometry and found that
      these do not show sequence similarities with other proteins of bacterial
      cytoskeletons or the gliding proteins previously identified. Immunofluorescence
      and immunoelectron microscopy revealed that two components are localized at the
      bell and another that has the structure similar to the F(1)-ATPase beta subunit
      is localized at the tentacles.

PMID- 18042729
TI  - Epidermal growth factor receptor juxtamembrane region regulates allosteric
      tyrosine kinase activation.
AB  - Structural studies of the extracellular and tyrosine kinase domains of the
      epidermal growth factor receptor (ErbB-1) provide considerable insight into
      facets of the receptor activation mechanism, but the contributions of other
      regions of ErbB-1 have not been ascertained. This study demonstrates that the
      intracellular juxtamembrane (JM) region plays a vital role in the kinase
      activation mechanism. In the experiments described herein, the entire ErbB-1
      intracellular domain (ICD) has been expressed in mammalian cells to explore the
      significance of the JM region in kinase activity. Deletion of the JM region
      (DeltaJM) results in a severe loss of ICD tyrosine phosphorylation, indicating
      that this region is required for maximal activity of the tyrosine kinase domain.
      Coexpression of DeltaJM and dimerization-deficient kinase domain ICD mutants
      revealed that the JM region is indispensable for allosteric kinase activation and
      productive monomer interactions within a dimer. Studies with the intact receptor
      confirmed the role of the JM region in kinase activation. Within the JM region,
      Thr-654 is a known protein kinase C (PKC) phosphorylation site that modulates
      kinase activity in the context of the intact ErbB-1 receptor; yet, the mechanism
      is not known. Whereas a T654A mutation promotes increased ICD tyrosine
      phosphorylation, the phosphomimetic T654D mutant generates a 50% reduction in ICD
      tyrosine phosphorylation. Similar to the DeltaJM mutants, the T654D mutant ICD
      failed to interact with a wild-type monomer. This study reveals an integral role
      for the intracellular JM region of ErbB-1 in allosteric kinase activation.

PMID- 18042731
TI  - Potent inhibition of human apurinic/apyrimidinic endonuclease 1 by arylstibonic
      acids.
AB  - Human apurinic/apyrimidinic endonuclease (Ape1) plays an important role by
      processing the >10,000 highly toxic abasic sites generated in the genome of each
      cell every day. Ape1 has recently emerged as a target for inhibition, in that its
      overexpression in tumors has been linked with poor response to both radiation and
      chemotherapy and lower overall patient survival. Inhibition of Ape1 using siRNA
      or the expression of a dominant-negative form of the protein has been shown to
      sensitize cells to DNA-damaging agents, including various chemotherapeutic
      agents. However, potent small-molecule inhibitors of Ape1 remain to be found. To
      this end, we screened Ape1 against the NCI Diversity Set of small molecules and
      discovered aromatic nitroso, carboxylate, sulfonamide, and arylstibonic acid
      compounds with micromolar affinities for the protein. A further screen of a 37
      compound arylstibonic acid sublibrary identified ligands with IC(50) values in
      the range of 4 to 300 nM. The negatively charged stibonic acids act by a partial
      mixed mode and probably serve as DNA phosphate mimics. These compounds provide a
      useful scaffold for development of chemotherapeutic agents against Ape1.

PMID- 18042730
TI  - Directed selection of a conformational antibody domain that prevents mature
      amyloid fibril formation by stabilizing Abeta protofibrils.
AB  - The formation of amyloid fibrils is a common biochemical characteristic that
      occurs in Alzheimer's disease and several other amyloidoses. The unifying
      structural feature of amyloid fibrils is their specific type of beta-sheet
      conformation that differentiates these fibrils from the products of normal
      protein folding reactions. Here we describe the generation of an antibody domain,
      termed B10, that recognizes an amyloid-specific and conformationally defined
      epitope. This antibody domain was selected by phage-display from a recombinant
      library of camelid antibody domains. Surface plasmon resonance, immunoblots, and
      immunohistochemistry show that this antibody domain distinguishes Abeta amyloid
      fibrils from disaggregated Abeta peptide as well as from specific Abeta
      oligomers. The antibody domain possesses functional activity in preventing the
      formation of mature amyloid fibrils by stabilizing Abeta protofibrils. These data
      suggest possible applications of B10 in the detection of amyloid fibrils or in
      the modulation of their formation.

PMID- 18042732
TI  - 2-[2-(3,4-dichloro-phenyl)-2,3-dihydro-1H-isoindol-5-ylamino]-nicotinic acid (PD
      307243) causes instantaneous current through human ether-a-go-go-related gene
      potassium channels.
AB  - Long and short QT syndromes associated with loss and gain of human ether-a-go-go
      related gene (hERG) channel activity, respectively, can cause life-threatening
      arrhythmias. As such, modulation of hERG channel activity is an important
      consideration in the development of all new therapeutic agents. In the present
      study, we investigated the mechanisms of action of 2-[2-(3,4-dichloro-phenyl)-2,3
      dihydro-1H-isoindol-5-ylamino]-nicotinic acid (PD-307243), a known hERG channel
      activator, on hERG channels stably expressed in Chinese hamster ovary (CHO) cells
      using the patch-clamp technique. In the whole-cell recordings, the extracellular
      application of PD-307243 concentration-dependently increased the hERG current and
      markedly slowed hERG channel deactivation and inactivation. PD-307243 had no
      effect on the selectivity filter of hERG channels. The activity of PD-307243 was
      use-dependent. PD-307243 (3 and 10 muM) induced instantaneous hERG current with
      little decay at membrane potentials from -120 to -40 mV. At more positive
      voltages, PD-307243 induced an I(to)-like upstroke of hERG current. The actions
      of PD-307243 on the rapid component of delayed rectifier K(+) current (I(Kr)) in
      rabbit ventricular myocytes were similar to those observed in hERG channel
      transfected CHO cells. Inside-out patch experiments revealed that PD-307243
      increased hERG tail currents by 2.1 +/- 0.6 (n = 7) and 3.4 +/- 0.3-fold (n = 4)
      at 3 and 10 muM, respectively, by slowing the channel deactivation but had no
      effect on channel activation. During a voltage-clamp protocol using a prerecorded
      cardiac action potential, 3 muM PD-307243 increased the total potassium ions
      passed through hERG channels by 8.8 +/- 1.0-fold (n = 5). Docking studies suggest
      that PD-307243 interacts with residues in the S5-P region of the channel.

PMID- 18042733
TI  - Progesterone receptor (PR) isoforms PRA and PRB differentially regulate
      expression of the breast cancer resistance protein in human placental
      choriocarcinoma BeWo cells.
AB  - Breast cancer resistance protein (BCRP) plays a significant role in drug
      disposition and in conferring multidrug resistance in cancer cells. Previous
      studies have shown that steroid hormones such as 17beta-estradiol and
      progesterone can affect BCRP expression in cancer cells. In this study, we
      investigated the molecular mechanism by which BCRP expression in human placental
      choriocarcinoma BeWo cells is regulated by progesterone. Transfection of the
      progesterone receptor (PR) isoforms PRA and PRB resulted in a similarly increased
      expression of PRA and PRB, respectively. However, progesterone significantly
      increased BCRP expression and activity only in PRB-transfected cells. This
      stimulatory effect of progesterone was abrogated by the PR antagonist
      mifepristone (RU-486). Consistently, transcriptional activity of the BCRP
      promoter was induced 2- to 6-fold by 10(-8) to 10(-5) M progesterone in PRB
      transfected cells. Progesterone had little effect on BCRP expression and activity
      and transcriptional activity of the BCRP promoter in PRA-transfected cells;
      however, cotransfection of PRA and PRB significantly decreased the progesterone
      response compared with that in cells transfected with only PRB. Mutations in a
      novel progesterone response element (PRE) identified between -243 to -115 bp of
      the BCRP promoter region significantly attenuated the progesterone-response in
      PRB-transfected cells, and deletion of the PRE nearly completely abrogated the
      progesterone effect. Specific binding of both PRA and PRB to the BCRP promoter
      through the identified PRE was confirmed using the electrophoretic mobility shift
      assay. Collectively, progesterone induces BCRP expression in BeWo cells via PRB
      but not PRA. PRA represses the PRB activity. Thus, PRA and PRB differentially
      regulate BCRP expression in BeWo cells.

PMID- 18042734
TI  - Identification and characterization of two amino acids critical for the substrate
      inhibition of human dehydroepiandrosterone sulfotransferase (SULT2A1).
AB  - Substrate inhibition is a characteristic feature of many cytosolic
      sulfotransferases. The differences between the complex structures of SULT2A1/DHEA
      and SULT2A1/PAP or SULT2A1/ADT (Protein Data Bank codes are 1J99, 1EFH, and 1OV4,
      respectively) have enabled us to elucidate the specific amino acids responsible
      for substrate inhibition. Based on the structural analyses, substitution of the
      smaller residue alanine for Tyr-238 (Y238A) significantly increases the K(i)
      value for dehydroepiandrosterone (DHEA) and totally eliminates substrate
      inhibition for androsterone (ADT). In addition, Met-137 was proposed to regulate
      the binding orientations of DHEA and ADT in SULT2A1. Complete elimination or
      regeneration of substrate inhibition for SULT2A1 with DHEA or ADT as substrate,
      respectively, was demonstrated with the mutations of Met-137 on Y238A mutant.
      Analysis of the Met-137 mutants and Met-137/Tyr-238 double mutants uncovered the
      relationship between substrate binding orientations and inhibition in SULT2A1.
      Our data indicate that, in the substrate inhibition mode, Tyr-238 regulates the
      release of bound substrate, and Met-137 controls substrate binding orientation of
      DHEA and ADT in SULT2A1. The proposed substrate inhibition mechanism is further
      confirmed by the crystal structures of SULT2A1 mutants at Met-137. We propose
      that both substrate binding orientations exhibited substrate inhibition. In
      addition, a corresponding residue in other cytosolic sulfotransferases was shown
      to have a function similar to that of Tyr-238 in SULT2A1.

PMID- 18042735
TI  - Activation of the dual-leucine-zipper-bearing kinase and induction of beta-cell
      apoptosis by the immunosuppressive drug cyclosporin A.
AB  - Post-transplant diabetes is an untoward effect often observed under
      immunosuppressive therapy with cyclosporin A. Besides the development of
      peripheral insulin resistance and a decrease in insulin gene transcription, a
      beta-cell toxic effect has been described. However, its molecular mechanism
      remains unknown. In the present study, the effect of cyclosporin A and the dual
      leucine-zipper-bearing kinase (DLK) on beta-cell survival was investigated.
      Cyclosporin A decreased the viability of the insulin-producing pancreatic islet
      cell line HIT in a time- and concentration-dependent manner. Upon exposure to the
      immunosuppressant fragmentation of DNA, the activation of the effector caspase-3
      and a decrease of full-length caspase-3 and Bcl(XL) were observed in HIT cells
      and in primary mature murine islets, respectively. Cyclosporin A and tacrolimus,
      both potent inhibitors of the calcium/calmodulin-dependent phosphatase
      calcineurin, stimulated the enzymatic activity of cellular DLK in an in vitro
      kinase assay. Immunocytochemistry revealed that the overexpression of DLK but not
      its kinase-dead mutant induced apoptosis and enhanced cyclosporin A-induced
      apoptosis to a higher extent than the drug alone. Moreover, in the presence of
      DLK, the effective concentration for cyclosporin A-caused apoptosis was similar
      to its known IC(50) value for the inhibition of calcineurin activity in beta
      cells. These data suggest that cyclosporin A through inhibition of calcineurin
      activates DLK, thereby leading to beta-cell apoptosis. This action may thus be a
      novel mechanism through which cyclosporin A precipitates post-transplant
      diabetes.

PMID- 18042736
TI  - An intracellular allosteric site for a specific class of antagonists of the CC
      chemokine G protein-coupled receptors CCR4 and CCR5.
AB  - A novel mechanism for antagonism of the human chemokine receptors CCR4 and CCR5
      has been discovered with a series of small-molecule compounds that seems to
      interact with an allosteric, intracellular site on the receptor. The existence of
      this site is supported by a series of observations: 1) intracellular access of
      these antagonists is required for their activity; 2) specific, saturable binding
      of a radiolabeled antagonist requires the presence of CCR4; and 3) through
      engineering receptor chimeras by reciprocal transfer of C-terminal domains
      between CCR4 and CCR5, compound binding and the selective structure-activity
      relationships for antagonism of these receptors seem to be associated with the
      integrity of that intracellular region. Published antagonists from other chemical
      series do not seem to bind to the novel site, and their interaction with either
      CCR4 or CCR5 is not affected by alteration of the C-terminal domain. The precise
      location of the proposed binding site remains to be determined, but the known
      close association of the C-terminal domain, including helix 8, as a proposed
      intracellular region that interacts with transduction proteins (e.g., G proteins
      and beta-arrestin) suggests that this could be a generic allosteric site for
      chemokine receptors and perhaps more broadly for class A G protein-coupled
      receptors. The existence of such a site that can be targeted for drug discovery
      has implications for screening assays for receptor antagonists, which would need,
      therefore, to consider compound properties for access to this intracellular site.

PMID- 18042737
TI  - Effects of maternal diabetes on visual evoked potentials and early psychomotor
      development of the offspring.

PMID- 18042738
TI  - Metformin in heart failure.

PMID- 18042739
TI  - Islet autotransplantation restores normal glucose tolerance in a patient with
      chronic pancreatitis.

PMID- 18042740
TI  - Possible relevance of HLA-DRB1*0403 haplotype in insulin autoimmune syndrome
      induced by alpha-lipoic acid, used as a dietary supplement.

PMID- 18042741
TI  - The role of iron in diabetes and its complications: response to Swaminathan et
      al.

PMID- 18042742
TI  - On real-time estimates of blood glucose levels: response to Trevino.

PMID- 18042744
TI  - Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome
      in community-dwelling older adults: response to Reis et al.

PMID- 18042746
TI  - Strong association between time watching television and blood glucose control in
      children and adolescents with type 1 diabetes: response to Margeirsdottir et al.

PMID- 18042747
TI  - Effect of periodontitis on overt nephropathy and end-stage renal disease in type
      2 diabetes: response to Shultis et al.

PMID- 18042749
TI  - Metabolic syndrome in hypertensive patients: correlation between anthropometric
      data and laboratory findings: response to Bulhoes and Araujo.

PMID- 18042750
TI  - Consensus statement on the Worldwide Standardization of the Hemoglobin A1C
      Measurement: the American Diabetes Association, European Association for the
      Study of Diabetes, International Federation of Clinical Chemistry and Laboratory
      Medicine, and the International Diabetes Federation: response to the Consensus
      Committee.

PMID- 18042751
TI  - Corneal sensitivity is reduced and relates to the severity of neuropathy in
      patients with diabetes: response to Tavakoli et al.

PMID- 18042753
TI  - Lessons from the Avandia controversy: a new paradigm for the development of drugs
      to treat type 2 diabetes.

PMID- 18042754
TI  - Diabetes and obesity: part 1.

PMID- 18042755
TI  - Comment on: Cani et al. (2007) Metabolic endotoxemia initiates obesity and
      insulin resistance: Diabetes 56:1761-1772.

PMID- 18042757
TI  - Comment on: Chang et al. (2007) Association study of the genetic polymorphisms of
      the transcription factor 7-like 2 (TCF7L2) gene and type 2 diabetes in the
      Chinese population: Diabetes 56:2631-2637.

PMID- 18042759
TI  - Lost in translation: facing up to translational research.

PMID- 18042760
TI  - Genetic factors in type 2 diabetes: all in the (lipin) family.

PMID- 18042761
TI  - Genome-wide association: which do you want first: the good news, the bad news, or
      the good news?

PMID- 18042762
TI  - Acute fatal post-CABG low dose amiodarone lung toxicity.
AB  - Amiodarone is one of the commonly used anti-arrhythmic agents with well
      recognized chronic pulmonary toxicity. We present our experience of a patient
      with a fatal outcome after coronary artery bypass grafting and a short course of
      amiodarone treatment with a low total cumulative dose for the treatment of
      postoperative atrial fibrillation. Necropsy revealed diffuse pulmonary damage due
      to acute amiodarone lung toxicity.

PMID- 18042763
TI  - Off-pump pericardiectomy using an ultrasonic scalpel and a heart positioner.
AB  - The surgical treatment of constrictive pericarditis often requires extensive
      pericardial dissection under cardiopulmonary bypass. We performed a
      pericardiectomy in a patient with constrictive pericarditis without
      cardiopulmonary bypass, with assistance of a sternal retractor and a suction
      heart positioner. The severely calcified pericardium, which adhered tightly to
      the epicardium, was dissected with an ultrasonic scalpel. The operation was
      completed without blood transfusion. There was no malignant arrhythmia.

PMID- 18042764
TI  - Papillary fibroelastoma of the left ventricle: report of two cases.
AB  - Papillary fibroelastoma is a relatively rare cardiac tumor. We report two cases
      of papillary fibroelastoma. The first case involved a 45-year-old woman who
      presented with rheumatic valves and three tumors developing from the papillary
      muscle and left ventricle. The second case involved a 68-year-old man who was
      asymptomatic and whose tumor was detected incidentally on echocardiogram. Both
      cases were treated surgically. An additional 71 cases of papillary fibroelastoma
      reported in the medical literature in Japan are reviewed.

PMID- 18042766
TI  - The choice of valve prosthesis: are the guidelines for everyone?

PMID- 18042765
TI  - Combined coronary artery re-operation and pulmonary resection for hemoptysis.
AB  - We present a 59-year-old woman who underwent combined pulmonary resection for
      bronchiectasis with massive, recurrent hemoptysis and redo coronary artery
      bypass. She had previously been hospitalized four times for massive hemoptysis.
      She had also undergone coronary artery bypass and had symptomatic severe graft
      disease. We performed simultaneous right middle lobectomy and redo triple bypass.
      At surgery, lobectomy was performed before heparinization, then redo bypass was
      performed using on-pump cardiopulmonary bypass. The postoperative course was
      uneventful.

PMID- 18042767
TI  - Left ventricular hypertrophy and remodeling after aortic valve replacement.
AB  - Left ventricular geometric remodeling and regression of hypertrophy were assessed
      after aortic valve replacement with a mechanical prosthesis in 37 patients with
      aortic stenosis and 39 with aortic insufficiency, aged 54.2 +/- 14.3 and 52.6 +/-
      16.6 years, respectively. The follow-up period was 2 years. In patients with
      aortic insufficiency, ejection fraction increased from 54.4 +/- 3.5
      preoperatively to 59.6 +/- 3.4 after 6 months and 61.7 +/- 2.7 after 2 years. In
      patients with aortic stenosis, ejection fraction increased from 56.6 +/- 5.1
      preoperatively to 63.9 +/- 4.4 after 6 months and 71.7 +/- 4.1 after 2 years.
      Geometric remodeling, regression of hypertrophy, and increased ejection fraction
      of the left ventricle were similar in both groups at 6 months after surgery, but
      after 2 years of follow-up, greater improvement was found in patients who had
      undergone valve replacement for aortic stenosis.

PMID- 18042768
TI  - Glutamine improves myocardial function following ischemia-reperfusion injury.
AB  - Myocardial ischemia-reperfusion injury is common during cardiac procedures.
      Glutamine may protect the myocardium by preserving metabolic substrates.
      Glutamine (0.52 g x kg(-1)) or Ringer's lactate solution (control group) was
      administered intraperitoneally to 63 Sprague-Dawley rats at 4 or 18 hours prior
      to experimental ischemia and reperfusion. The hearts were excised and perfused on
      an isolated working heart model, exposed to global ischemia for 15 min and
      reperfusion for 1 hour. Left atrial pressure, mean aortic pressure, cardiac flow,
      coronary flow, and aortic output were measured 15 min before ischemia and every
      15 min during reperfusion. There was significantly better cardiac output in the
      glutamine pretreated groups. Pretreatment at 4 hours before the experiment was
      superior to pretreatment at 18 hours, with better maintenance of cardiac output
      and coronary flow. The enhanced protective effect of pretreatment at 4 hours
      highlights the importance of timing, and suggests a potential clinical benefit.

PMID- 18042769
TI  - Minimally invasive right posterior minithoracotomy for open-heart procedures.
AB  - A right posterior minithoracotomy was evaluated in 123 selected patients between
      November 2002 and August 2006. Their ages ranged from 1.5 to 32 years (mean, 7.8
      years) and weights ranged from 12.3 to 61.6 kg (mean, 23.3 kg). Pathology
      included atrial septal defect in 81 (66%), ventricular septal defect in 16 (13%),
      and 24 other (mainly valve) defects. All patients had a strictly posterior right
      minithoracotomy through the 4(th) or 5(th) right intercostal space, with a 7-9-cm
      skin incision. There was no mortality or procedure-related morbidity. The mean
      cardiopulmonary bypass time was 68 min, ischemic time was 47 min, and 47 (38%)
      patients were extubated on the operating table. The mean hospital stay was 4.3
      days and it was < 5 days in 108 (88%) patients. A cosmetically fine scar was
      achieved in all patients. The right posterior minithoracotomy is a safe,
      cosmetically superior, and cost-effective approach for selected open-heart
      procedures.

PMID- 18042770
TI  - Minimal vs median sternotomy for aortic valve replacement.
AB  - The aim of this study was to compare postoperative outcomes in patients
      undergoing aortic valve replacement through a ministernotomy or conventional
      sternotomy. Sixty patients were randomized into 2 groups of 30 each: group 1 had
      a full sternotomy and group 2 had a ministernotomy. Pain was evaluated on a daily
      basis, pulmonary function tests were performed perioperatively. The skin incision
      was shorter in group 2 (7.17 vs 24.50 cm in group 1). There was significantly
      less mediastinal drainage in group 2 (233 vs 590 mL in 24 hours in group 1).
      Group 1 patients had more blood transfusions and longer ventilation time. In
      group 1, 96.7% experienced severe pain, whereas 93.3% in group 2 reported minimal
      pain. Hospital stay was 17.7 days in group 1 and 8.0 days in group 2. The
      ministernotomy had a cosmetic advantage, less blood loss and transfusion
      requirement, greater sternal stability, better respiratory function, and earlier
      extubation and hospital discharge.

PMID- 18042771
TI  - Prosthetic valve replacement in adolescents with rheumatic heart disease.
AB  - To assess long-term survival and anticoagulant-related complications after
      mechanical valve replacement in adolescents with rheumatic heart disease, 88
      patients aged <or= 18 years were prospectively followed up for 10 years (404.2
      patient-years). There were 58 (65.9%) boys and 30 (34.1%) girls, with a mean age
      of 15.4 +/- 2.1 years. Mitral regurgitation was detected in 39 (44.3%) patients,
      and both mitral and aortic regurgitation in 15 (17%). Ball valves were inserted
      in 52 (59.1%) patients, bileaflet valves in 31 (35.2%), and single-disc valves in
      5 (5.7%). There were 4 (4.5%) hospital deaths and 11 late deaths. Patient
      survival at 30 days, 3 months, 1, 5, and 10 years was 95.5%, 93.2%, 87.5%, 82.9%,
      and 82.9%, respectively. Mechanical valve thrombosis occurred in 4 patients; it
      was fatal in 3 of them. Three patients died from stroke. Severe hemorrhage
      required hospital admission in 4 (4.5%) patients. Mechanical valve replacement in
      adolescents, with careful follow-up and anticoagulation, has acceptable long-term
      results.

PMID- 18042772
TI  - Surgical experience of coarctation of the aorta in infants and young children.
AB  - We evaluated the effectiveness of surgical treatment for coarctation of the aorta
      in infants and young children, based on our experience over 7 years. From March
      1999 to December 2005, 168 cases of coarctation of the aorta in patients aged 21
      days to 3 years were treated by end-to-end, extended end-to-end, or extended end
      to-side ascending aorta and aortic arch anastomosis. The mortality rate was 0.6%.
      In 138 (82%) patients, the pressure in the lower extremity was higher than in the
      upper extremity. During 6-24 months of follow-up, hoarseness appeared in 6
      patients. Echocardiography revealed stenosis of the end-to-end anastomosis in
      only 2 patients. We suggest that the best option for surgical treatment of
      coarctation of the aorta with associated cardiac malformations is a one-stage
      procedure using a median sternotomy approach. It is better to perform extended
      end-to-end anastomosis or anastomosis between the distal descending aorta and the
      left wall of the ascending aorta, or to extend this anastomosis to the transverse
      arch.

PMID- 18042773
TI  - Age deteriorates palmar microcirculation following radial artery harvesting.
AB  - The effect of age as a risk factor for deterioration of palmar microcirculation
      after radial artery harvesting for coronary revascularization is unknown. In 114
      patients aged 61.7 +/- 6.7 years undergoing radial artery harvesting, superficial
      and deep tissue oxygen saturation, postcapillary venous filling, and capillary
      blood flow were determined using a combined laser Doppler spectrophotometry
      system 25 +/- 5 months after surgery. Superficial and deep oxygen saturation at
      the harvested thenar eminence decreased with age. In the nondonor hand, oxygen
      saturation declined in the first and second digits. Postcapillary venous filling
      pressure in both thenars increased with age. It was concluded that neurological
      complications do not correlate with age. Palmar tissue oxygen saturation, palmar
      capillary blood flow, and blood velocity decrease, while postcapillary venous
      filling pressure significantly increases with age. Radial artery harvesting for
      coronary revascularization does not compromise palmar microcirculation to the
      same extent as age. A cut-off value of <or= 67 years was determined by
      microcirculatory assessment; beyond this, significant deterioration of palmar
      microcirculation is more likely to occur.

PMID- 18042774
TI  - Anticoagulation for prosthetic heart valves in pregnancy. Is there an answer?
AB  - The aim of this retrospective study was to compare the different anticoagulation
      regimens used in pregnant women with prosthetic heart valves. We reviewed 196
      pregnancies in 110 women from 1974 to 2000. The patients were divided into two
      groups: group 1 (142 pregnancies) had warfarin throughout pregnancy; and in group
      2 (54 pregnancies), warfarin was replaced by subcutaneous heparin during the
      first trimester and last two weeks of pregnancy. There were no maternal
      complications in 129 pregnancies in group 1 and 44 in group 2. There were
      significantly fewer normal births in group 1 (56; 39.4%) compared to group 2 (39;
      72.2%). Group 1 had a significantly higher rate of spontaneous abortion (46.5% vs
      14.8%), but group 2 had a higher rate of valve thrombosis. In group 1, women with
      a warfarin requirement < 5 mg had a lower rate of spontaneous abortion. Warfarin
      is an effective anticoagulant in pregnant women with mechanical valves but it
      results in significant fetal loss when the dose is > 5 mg. Heparin is a less
      effective anticoagulant resulting in more maternal complications, but it is more
      protective of the fetus.

PMID- 18042775
TI  - Anticoagulation in pregnancy with mechanical heart valves: 10-year experience.
AB  - Anticoagulation in pregnancy was evaluated in 33 women with a mechanical heart
      valve prosthesis who had 53 pregnancies between 1994 and 2006. Their mean age at
      valve operation was 24.4 +/- 5.4 years, and 22 (67%) had isolated mitral valve
      disease. Of these patients, 22 had a single pregnancy, 5 had 2 pregnancies, 3 had
      3, and 3 had 4. In 43 pregnancies, the patients took warfarin throughout; in the
      other 10, heparin was used in the first trimester followed by warfarin until the
      last 15 days. Mean international normalized ratio and warfarin levels before,
      during, and after pregnancy were similar. Complications occurred in 3 (6%) women
      who had thrombosed valves: 2 (20%) in the heparin group and 1 (2%) who had
      warfarin only. Live births resulted from 37 (70%) pregnancies. There were
      significantly more abortions in the heparin group (6; 60%) than the warfarin
      group (8; 19%). Hemorrhage requiring transfusion occurred in 2 (5%) patients in
      the warfarin group. All live births resulted in healthy babies. It was concluded
      that anticoagulation with warfarin is safe during pregnancy in women with
      mechanical heart valves.

PMID- 18042776
TI  - Cardiac troponin I concentrations during on-pump coronary artery surgery.
AB  - Perioperative myocardial infarction remains a frequent complication after
      coronary artery bypass grafting, and is associated with a poor prognosis. This
      retrospective study compared cardiac troponin I concentrations after on-pump
      bypass grafting in 2 groups of patients: 100 operated on using a single-clamp
      technique to perform anastomoses, and 80 operated on using a double-clamp
      technique. Postoperative cardiac troponin I levels were not significantly
      different between groups. It was concluded that the double-clamp technique did
      not reduce the incidence of myocardial infarction after elective on-pump coronary
      artery bypass grafting, and use of a single clamp is safe with no adverse effect
      on postoperative outcome.

PMID- 18042777
TI  - Learning curve of arch-first technique analyzed by cumulative sum.
AB  - This study was undertaken to verify efficacy of the arch-first technique in the
      light of its learning curve. From April 2002 to September 2005, 10 consecutive
      elective cases of total arch replacement were retrospectively examined. The
      learning curve of the arch-first technique was constructed using cumulative sum
      analysis. There were no operative deaths. The mean deep hypothermic circulatory
      arrest time was 28.4 +/- 13.7 min, the lower body ischemic time was 91.3 +/- 35.1
      min, aortic cross clamp time was 133.2 +/- 18.1 min, cardiopulmonary bypass time
      was 198.8 +/- 21.5 min, and operation time was 383 +/- 24 min. The durations of
      deep hypothermic circulatory arrest, bypass, and operation were under the 90%
      lower alarm line in all 10 cases. The lower body ischemic time and cardiac arrest
      time were between the 80% upper and lower alert lines. Cumulative sum analysis of
      total arch replacement using the arch-first technique showed satisfactory rates
      of improvement in reconstruction of the 3 arch vessels, cardiopulmonary bypass
      time, and overall mortality.

PMID- 18042778
TI  - Novel method of thoracoscopic surgery for giant bulla without residual cavity.
AB  - A giant bulla is generally resected by thoracoscopic surgery. Resection using an
      automated stapling device is popular, however, a number of cartridges may be
      consumed and a cavity is sometimes left remaining, especially when resecting wide
      based lesions. To establish a thoracoscopic surgical procedure that results in no
      residual cavity, we developed a method in which the roof of the bulla is resected
      first, followed by resection of the pulmonary parenchyma, including the base of
      the bulla, using a stapling device. Exposure of the base by first removing the
      roof facilitates determination of the resection line. Between 2003 and 2005, the
      procedure was attempted in 6 patients, which included one bilateral case.
      Conversion to a minithoracotomy was required in one patient because of bulla
      thickening. The operating time ranged from 80 to 150 min (median, 135 min) in the
      other 6 cases. Postoperative chest drainage ranged from 2 to 13 days (median, 3
      days), and postoperative hospital stay was 5 to 18 days (median, 6 days). No
      adverse events occurred. We found this procedure to be simple and useful for
      complete resection of giant bullae.

PMID- 18042779
TI  - Perforation of a substernal interposed ileocolon caused by right thoracic
      herniation.
AB  - Perforation of a retrosternal interposed ileocolon is rare. We present a case of
      perforation of the interposed colon on the ninth postoperative day, which
      subsequently herniated to the right pleural space. We suggest that the dilated
      haustral trapping and the associated "waterfall" effect may have resulted in
      incarceration of the colon. Careful dissection of the pleura in order to create a
      retrosternal tunnel, and the use of a suitable length of an esophageal substitute
      could prevent this complication.

PMID- 18042780
TI  - A rare complication of pneumonectomy: hiatal hernia associated with gastric
      volvulus.
AB  - A rare case of intrathoracic gastric herniation resulting in intermittent gastric
      volvulus was observed in a 69-year-old female patient five months after left
      pneumonectomy for lung cancer. The mechanism of post-pneumonectomy intermittent
      gastric volvulus and the techniques of surgical repair are discussed.

PMID- 18042781
TI  - Aortic root replacement in Behcet disease.
AB  - The patient presented with a history of recurrent aphthous stomatitis, genital
      ulceration, and a family history of positive for collagen disease.
      Echocardiography and retrograde aortography revealed aneurysm formation of the
      sinus of Valsalva, and dilatation of the aortic valve annulus with severe aortic
      regurgitation. On diagnosis of an aneurysm of the sinus of Valsalva and aortic
      regurgitation associated with Behcet's disease, aortic root replacement with the
      modified Bentall technique was successfully performed.

PMID- 18042782
TI  - Tracheomalacia in a patient with unilateral pulmonary and renal agenesis.
AB  - We report the case of an eight-month-old boy with tracheomalacia secondary to
      impingement by the right pulmonary artery, together with congenital agenesis of
      the left lung and the left kidney. Aortopexy and right pulmonary arterypexy were
      successful in improving lung function by more than 100%, and the patient remained
      free of complications in the long term.

PMID- 18042783
TI  - Aortic and mitral valve replacement in a patient with hemophilia B.
AB  - A 25-year-old man with factor IX deficiency had an aortic and mitral valve
      replacement using a 2M Starr Edwards valve in the mitral position and a 22
      Medtronic valve in the aortic position under cover of factor IX concentrate. The
      surgical procedure and the immediate postoperative period were uneventful except
      for a pericardial effusion which required a pericardiostomy. He was
      anticoagulated with heparin in the immediate postoperative period while the
      factor IX concentrate was being administered. Oral anticoagulation with
      acenocoumarol (Acitrom) was started, maintaining the international normalized
      ratio between 1.5 and 2. He was doing well at follow-up 9 months later.

PMID- 18042784
TI  - Safe innominate artery cannulation for cardiopulmonary bypass in neonates.
AB  - To reduce the neurological complications of deep hypothermic circulatory arrest,
      continuous cerebral perfusion was introduced, either by direct innominate artery
      cannulation or by a tubular prosthesis. This second option, used in our clinical
      experience, has been extended to applications other than aortic arch
      reconstruction, to facilitate cardiopulmonary bypass in small neonates (< 3.0 kg)
      with complex congenital heart defects, and to facilitate postoperative
      extracorporeal membrane oxygenation.

PMID- 18042785
TI  - Chordal replacement with temporary Alfieri stitch for anterior leaflet prolapse.
AB  - In mitral valve regurgitation due to anterior leaflet prolapse and other
      complicated lesions, chordal replacement with expanded polytetrafluoroethylene is
      widely practiced. The most troublesome aspects of this procedure are the
      determination of the necessary length of the artificial chorda and the tying of
      the knot. We describe a simple technique for artificial chordal replacement using
      an Alfieri stitch, that has been successfully applied to 10 patients with
      anterior leaflet prolapse.

PMID- 18042786
TI  - Importance of perioperative blood glucose management in cardiac surgical
      patients.
AB  - Tight blood glucose control has become a therapeutic goal for anesthetic
      management of patients undergoing cardiovascular surgery. We discuss the evidence
      for a link between blood glucose levels and rates of morbidity and mortality in
      cardiac surgical patients in the intensive care unit. Hyperglycemia per se has
      been associated with higher rates of deep wound infection, neurologic, renal, and
      cardiac complications following surgery, as well as longer intensive care unit
      stay. We review the specifics of glucose management in patients undergoing
      cardiac surgery and hypothermic cardiopulmonary bypass, including the role that
      insulin may play in regulating blood glucose levels intraoperatively and the
      relationship between insulin and outcome.

PMID- 18042787
TI  - Emergency closed mitral valvotomy with transesophageal echocardiographic
      guidance.

PMID- 18042788
TI  - An iatrogenic bronchial foreign body.

PMID- 18042789
TI  - Feeding artery of giant left atrial myxoma visualized on computed tomography.

PMID- 18042790
TI  - Papaverine hydrodissection of internal thoracic artery.

PMID- 18042791
TI  - Toward extending the educational interpreter performance assessment to cued
      speech.
AB  - The Educational Interpreter Performance Assessment (EIPA) is as an important
      research tool for examining the quality of interpreters who use American Sign
      Language or a sign system in classroom settings, but it is not currently
      applicable to educational interpreters who use Cued Speech (CS). In order to
      determine the feasibility of extending the EIPA to include CS, a pilot EIPA test
      was developed and administered to 24 educational CS interpreters. Fifteen of the
      interpreters' performances were evaluated two to three times in order to assess
      reliability. Results show that the instrument has good construct validity and
      test-retest reliability. Although more interrater reliability data are needed,
      intrarater reliability was quite high (0.9), suggesting that the pilot test can
      be rated as reliably as signing versions of the EIPA. Notably, only 48% of
      interpreters who formally participated in pilot testing performed at a level that
      could be considered minimally acceptable. In light of similar performance levels
      previously reported for interpreters who sign (e.g., Schick, Williams, &
      Kupermintz, 2006), these results suggest that interpreting services for deaf and
      hard-of hearing students, regardless of the communication option used, are often
      inadequate and could seriously hinder access to the classroom environment.

PMID- 18042792
TI  - Hyperlink format, categorization abilities and memory span as contributors to
      deaf users hypertext access.
AB  - Sixty deaf and hearing students were asked to search for goods in a Hypertext
      Supermarket with either graphical or textual links of high typicality, frequency,
      and familiarity. Additionally, they performed a picture and word categorization
      task and two working memory span tasks (spatial and verbal). Results showed that
      deaf students were faster in graphical than in verbal hypertext when the number
      of visited pages per search trial was blocked. Regardless of stimuli format,
      accuracy differences between groups did not appear, although deaf students were
      slower than hearing students in both Web search and categorization tasks
      (graphical or verbal). No relation between the two tasks was found. Correlation
      analyses showed that deaf students with higher spatial span were faster in
      graphical Web search, but no correlations emerged between verbal span and verbal
      Web search. A hypothesis of different strategies used by the two groups for
      searching information in hypertext is formulated. It is suggested that deaf users
      use a visual-matching strategy more than a semantic approach to make navigation
      decisions.

PMID- 18042793
TI  - Eradication of disseminated leukemia in a syngeneic murine leukemia model using
      pretargeted anti-CD45 radioimmunotherapy.
AB  - We describe the use of pretargeted radioimmunotherapy (PRIT) using an anti-murine
      CD45 antibody-streptavidin (SA) conjugate followed by radiobiotin to deliver
      radiation selectively to murine hematolymphoid tissues, which may potentially
      augment the efficacy and decrease the toxicity of radioimmunotherapy for
      disseminated murine leukemia. Biodistribution and therapeutic results
      demonstrated high target organ to nontarget organ ratios of radioactivity and
      significant long-term survival in leukemic mice using PRIT. These data suggest
      that anti-CD45 PRIT using an anti-CD45-SA conjugate in a syngeneic murine model
      of disseminated leukemia may be more effective and less toxic than directly
      labeled monoclonal antibodies.

PMID- 18042795
TI  - Splenic red pulp lymphoma with numerous basophilic villous lymphocytes: a
      distinct clinicopathologic and molecular entity?
AB  - The presence of circulating villous lymphocytes (VLs) in lymphoma patients
      usually points to splenic marginal zone B-cell lymphoma (SMZL), even if the VLs
      can be found occasionally in other small B-cell lymphomas. However, those cells
      are variably described, and detailed cytologic characterization is often lacking.
      We identified lymphoma cases with numerous basophilic VLs among the large group
      of splenic lymphoma with VLs, and for further delineation, 37 cases with this
      particular cytology were analyzed. Patients, predominantly older men, presented
      with moderate lymphocytosis and splenomegaly without pancytopenia. The monoclonal
      B cells expressed IgM + D, IgM + G, IgM or IgG, as well as CD76 and CD11c,
      frequently CD103, and rarely CD123. Spleen sections were peculiar, with atrophic
      white pulp and a monomorphic diffuse lymphoma infiltration in a congested red
      pulp. Bone marrow infiltration was interstitial and intrasinusoidal without
      extensive fibrosis. Cytogenetic analysis showed a frequent absence of clonal
      aberrations (68%). Most cases (79%) were IgH mutated, with an overrepresentation
      of V(H)3 and V(H)4 gene families. These results, as well as the clinical
      evolution, show that those lymphoma cases represent a homogeneous group distinct
      from SMZL and reminiscent of hairy cell leukemia variant, perhaps corresponding
      to a separate lymphoma entity.

PMID- 18042794
TI  - Distinct characteristics of signal transduction events by histamine-releasing
      factor/translationally controlled tumor protein (HRF/TCTP)-induced priming and
      activation of human basophils.
AB  - We previously identified a negative correlation between histamine release to
      histamine releasing factor/translationally controlled tumor protein (HRF/TCTP)
      and protein levels of the Src homology 2 domain-containing inositol 5'
      phosphatase (SHIP) in basophils. We have also demonstrated that HRF/TCTP primes
      basophils to release mediators. The purpose of this study was to begin
      characterization of signal transduction events directly induced by HRF/TCTP and
      to investigate these events when HRF/TCTP is used as a priming agent for human
      basophil histamine release. Highly purified human basophils were examined for
      surface expression of bound HRF/TCTP, changes in calcium, and phosphorylation of
      Akt, mitogen-activated protein kinase kinase (MEK), extracellular signal
      regulated kinase (ERK), Syk, and FcepsilonRIgamma. Results showed that basophils
      from all donors bound HRF/TCTP. There was a biphasic calcium response to
      HRF/TCTP, which corresponded to the magnitude of histamine release. Furthermore,
      those donors who have direct histamine release when exposed to HRF/TCTP (HRF/TCTP
      responder [HRF/TCTP-R] donors) have phosphorylation of Syk, Akt, MEK, and ERK.
      Remarkably, basophils from HRF/TCTP-nonresponder (HRF/TCTP-NR) donors do not show
      phosphorylation of these molecules. This finding is different from IL-3, which
      also primes basophils for histamine release, but does show phosphorylation of
      these events. We conclude that priming induced by HRF/TCTP is distinct from that
      induced by IL-3.

PMID- 18042796
TI  - Long-term imatinib therapy promotes bone formation in CML patients.
AB  - Imatinib inhibits tyrosine kinases important in osteoclast (c-Fms) and osteoblast
      (platelet-derived growth factor receptor [PDGF-R], c-Abl) function, suggesting
      that long-term therapy may alter bone homeostasis. To investigate this question,
      we measured the trabecular bone volume (TBV) in iliac crest bone biopsies taken
      from chronic myeloid leukemia (CML) patients at diagnosis and again after 2 to 4
      years of imatinib therapy. Half the patients (8 of 17) showed a substantive
      increase in TBV (> 2-fold), after imatinib therapy, with the TBV in the
      posttreatment biopsy typically surpassing the normal upper limit for the
      patient's age group. Imatinib-treated patients exhibited reduced serum calcium
      and phosphate levels with hypophosphatemia evident in 53% (9 of 17) of patients.
      In vitro, imatinib suppressed osteoblast proliferation and stimulated osteogenic
      gene expression and mineralized-matrix production by inhibiting PDGF receptor
      function. In PDGF-stimulated cultures, imatinib dose-dependently inhibited
      activation of Akt and Crk-L. Using pharmacologic inhibitors, inhibition of PI3
      kinase/Akt activation promoted mineral formation, suggesting a possible molecular
      mechanism for the imatinib-mediated increase in TBV in vivo. Further
      investigation is required to determine whether the increase in TBV associated
      with imatinib therapy may represent a novel therapeutic avenue for the treatment
      of diseases that are characterized by generalized bone loss.

PMID- 18042797
TI  - Hematopoietic origin of hepatic stellate cells in the adult liver.
AB  - Hepatic stellate cells are believed to play a key role in the development of
      liver fibrosis. Several studies have reported that bone marrow cells can give
      rise to hepatic stellate cells. We hypothesized that hepatic stellate cells are
      derived from hematopoietic stem cells. To test this hypothesis, we generated
      chimeric mice by transplantation of clonal populations of cells derived from
      single enhanced green fluorescent protein (EGFP)-marked Lin(-)Sca-1(+)c
      kit(+)CD34(-) cells and examined the histology of liver tissues obtained from the
      chimeric mice with carbon tetrachloride (CCl(4))-induced injury. After 12 weeks
      of CCl(4) treatment, we detected EGFP(+) cells in the liver, and some cells
      contained intracytoplasmic lipid droplets. Immunofluorescence analysis
      demonstrated that 50% to 60% of the EGFP(+) cells were negative for CD45 and
      positive for vimentin, glial fibrillary acidic protein, ADAMTS13, and alpha
      smooth muscle actin. Moreover, EGFP(+) cells isolated from the liver synthesized
      collagen I in culture. These phenotypes were consistent with those of hepatic
      stellate cells. The hematopoietic stem cell-derived hepatic stellate cells seen
      in male-to-male transplants revealed only one Y chromosome. Our findings suggest
      that hematopoietic stem cells contribute to the generation of hepatic stellate
      cells after liver injury and that the process does not involve cell fusion.

PMID- 18042798
TI  - Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host
      disease.
AB  - Graft-versus-host disease (GVHD) is a principal cause of morbidity following
      allogeneic hematopoietic cell transplantation (HCT). Standard therapy for GVHD,
      high-dose steroids, results in complete responses (CRs) in 35% of patients.
      Because tumor necrosis factor-alpha (TNFalpha) is an important effector of
      experimental GVHD, we treated patients with new-onset GVHD with steroids plus the
      TNFalpha inhibitor etanercept on a previously reported pilot trial (n = 20) and a
      phase 2 trial (n = 41). We compared their outcomes with those of contemporaneous
      patients with GVHD (n = 99) whose initial therapy was steroids alone. Groups were
      similar with respect to age, conditioning, donor, degree of HLA match, and
      severity of GVHD at onset. Patients treated with etanercept were more likely to
      achieve CR than were patients treated with steroids alone (69% vs 33%; P < .001).
      This difference was observed in HCT recipients of both related donors (79% vs
      39%; P = .001) and unrelated donors (53% vs 26%; P < .001). Plasma TNFR1 levels,
      a biomarker for GVHD activity, were elevated at GVHD onset and decreased
      significantly only in patients with CR. We conclude that etanercept plus steroids
      as initial therapy for acute GVHD results in a substantial majority of CRs. This
      trial was referenced at www.clinicaltrials.gov as NCT00141713.

PMID- 18042799
TI  - The LMP1 oncogene of EBV activates PERK and the unfolded protein response to
      drive its own synthesis.
AB  - The oncogene latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) without
      a ligand drives proliferation of EBV-infected B cells. Its levels vary in cells
      of clonal populations by more than 100-fold, which leads to multiple distinct
      activities of the oncogene. At intermediate levels it drives proliferation, and
      at high levels it inhibits general protein synthesis by inducing phosphorylation
      of eukaryotic initiation factor 2alpha (eIF2alpha). We have found that LMP1
      activates PERK to induce phosphorylation of eIF2alpha, which upregulates
      activating transcription factor 4 (ATF4) expression. ATF4, in turn,
      transactivates LMP1's own promoter. LMP1 activates not only PERK but also
      inositol requiring kinase 1 (IRE1) and ATF6, 3 pathways of the unfolded protein
      response (UPR). Increasing expression levels of LMP1 induced a dose-dependent
      increase in IRE1 activity, as measured by its "splicing" of XBP-1. These infected
      B cells secrete immunoglobins independent of the levels of LMP1, indicating that
      only a threshold level of XBP-1 is required for the secretion. These findings
      indicate that LMP1's activation of the UPR is a normal event in a continuum of
      LMP1's expression that leads both to stimulatory and inhibitory functions and
      regulates the physiology of EBV-infected B cells in multiple, unexpected modes.

PMID- 18042800
TI  - alpha2beta1 integrin expression in the tumor microenvironment enhances tumor
      angiogenesis in a tumor cell-specific manner.
AB  - To define the role of the alpha2beta1 integrin in pathologic angiogenesis, we
      investigated tumor-associated growth and angiogenesis in wild-type and alpha2
      null mice. Our findings reveal that the alpha2beta1 integrin plays an important
      role in angiogenesis via regulation of VEGFR1 expression. When challenged with
      B16F10 melanoma cells, mice lacking alpha2beta1 integrin ex-pression exhibit
      increased tumor angiogenesis associated with up-regulated VEGFR1 expression. In
      contrast, there was no alpha2beta1 integrin-dependent difference in the
      angiogenic response to Lewis lung carcinoma (LLC) cells. Interestingly, whereas
      B16F10 cells secrete high levels of placental growth factor (PLGF), LLC cells
      produce high levels of VEGF, but low levels of PLGF. The alpha2beta1 integrin
      dependent difference in angiogenesis was restored to LLC cells by expression of
      PLGF, strongly suggesting that the angiogenic phenotype and tumor growth in the
      alpha2-null host is dependent on specific interactions between the tumor cell and
      the genetically defined integrin repertoire of the host microenvironment. Thus
      integrin alpha2-null mice represent an example of genetic alterations of "the
      soil" determining response to the "seed."

PMID- 18042801
TI  - Complex inheritance pattern of dyskeratosis congenita in two families with 2
      different mutations in the telomerase reverse transcriptase gene.
AB  - Heterozygous mutations in the telomerase components TERT, the reverse
      transcriptase, and TERC, the RNA template, cause autosomal dominant dyskeratosis
      congenita due to telomere shortening. Anticipation, whereby the disease severity
      increases in succeeding generations due to inheritance of shorter telomeres, is a
      feature of this condition. Here we describe 2 families in which 2 TERT mutations
      are segregating. Both families contain compound heterozygotes. In one case the
      proband is homozygous for a novel mutation causing a P704S substitution, while
      his father's second allele encodes an H412Y mutation. The proband in the second
      family has mutant alleles Y846C and H876Q. Transfection studies show codominant
      expression of the mutated alleles with no evidence of a dominant negative effect
      or of intragenic complementation. Thus in these families the expression of both
      TERT alleles and the inherited telomere length contribute to the clinical
      phenotype.

PMID- 18042802
TI  - IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation
      of Akt to support T-cell survival.
AB  - Lymphocyte homeostasis requires coordination of metabolic processes with cellular
      energetic and biosynthetic demands but mechanisms that regulate T-cell metabolism
      are uncertain. We show that interleukin-7 (IL-7) is a key regulator of glucose
      uptake in T lymphocytes. To determine how IL-7 affects glucose uptake, we
      analyzed IL-7 signaling mechanisms and regulation of the glucose transporter,
      Glut1. The IL-7 receptor (IL-7R) stimulated glucose uptake and cell-surface
      localization of Glut1 in a manner that required IL-7R Y449, which promoted rapid
      signal transducer and activator of transcription 5 (STAT5) activation and a
      delayed yet sustained activation of Akt. Each pathway was necessary for IL-7 to
      promote glucose uptake, as Akt1(-/-) T cells or PI3-kinase inhibition and RNAi of
      STAT5 led to defective glucose uptake in response to IL-7. STAT5 and Akt acted in
      a linear pathway, with STAT5-mediated transcription leading to Akt activation,
      which was necessary for STAT5 and IL-7 to promote glucose uptake and prevent cell
      death. Importantly, IL-7 required glucose uptake to promote cell survival. These
      data demonstrate that IL-7 promotes glucose uptake via a novel signaling
      mechanism in which STAT5 transcriptional activity promotes Akt activation to
      regulate Glut1 trafficking and glucose uptake that is critical for IL-7 to
      prevent T-cell death and maintain homeostasis.

PMID- 18042803
TI  - Short-term BMP-4 treatment initiates mesoderm induction in human embryonic stem
      cells.
AB  - Human embryonic stem cells (hES cells) have unlimited self-renewal capacity and
      can differentiate into most, if not all, possible cell types. This unique
      property makes them valuable not only for investigation of early developmental
      processes, but also for regenerative medicine. Mesoderm-derived cardiac cells and
      hematopoietic cells both have the potential for various therapeutic applications.
      However, efficient induction of hES cell differentiation into mesoderm remains a
      challenge. Here, we showed that treatment of hES cells with bone morphogenetic
      protein-4 (BMP-4) exhibited differential effects: long-term treatment results in
      trophoblast and extra-embryonic endoderm differentiation, whereas short-term
      treatment can promote early mesoderm induction. The induction of mesoderm in hES
      cells occurs at a high efficiency as measured using several markers, such as
      Brachyury, WNT3, and MIXL1 expression. Moreover, these mesoderm progenitor cells
      can differentiate into cardiac and hematopoietic lineages in vitro. Further
      analysis showed that the mesoderm-inducing capacity of BMP-4 requires endogenous
      FGF and TGF-beta/Nodal/activin signaling activities. Thus, our results uncover a
      novel role for BMP-4 in regulation of hES cell differentiation and should provide
      insights into the mechanism of mesoderm induction in hES cells.

PMID- 18042804
TI  - Interleukin-27 directly induces differentiation in hematopoietic stem cells.
AB  - Interleukin (IL)-27, one of the most recently discovered IL-6 family cytokines,
      activates both the signal transducer and activator of transcription (STAT)1 and
      STAT3, and plays multiple roles in pro- and anti-inflammatory immune responses.
      IL-27 acts on various types of cells including T, B, and macrophage through the
      common signal-transducing receptor gp130 and its specific receptor WSX-1, but the
      effect of IL-27 on hematopoietic stem cells (HSCs) remains unknown. Here, we show
      that IL-27 together with stem cell factor (SCF) directly acts on HSCs and
      supports their early differentiation in vitro and in vivo. CD34(-/low)c-Kit(+)Sca
      1(+)lineage marker(-) (CD34(-)KSL) cells, a population highly enriched in mouse
      HSCs, were found to express both IL-27 receptor subunits. In vitro cultures of
      CD34(-)KSL cells with IL-27 and SCF resulted in an expansion of progenitors
      including short-term repopulating cells, while some of their long-term
      repopulating activity also was maintained. To examine its in vivo effect,
      transgenic mice expressing IL-27 were generated. These mice exhibited enhanced
      myelopoiesis and impaired B lymphopoiesis in the bone marrow with extramedullary
      hematopoiesis in the spleen. Moreover, IL-27 similarly acted on human CD34(+)
      cells. These results suggest that IL-27 is one of the limited cytokines that play
      a role in HSC regulation.

PMID- 18042805
TI  - Pim-1 and Pim-2 kinases are required for efficient pre-B-cell transformation by v
      Abl oncogene.
AB  - The precise mechanisms by which Abl oncogenes transform hematopoietic cells are
      unknown. We have examined the role of Pim kinases in v-Abl-mediated
      transformation. In v-Abl transformants, expression of Pim-1 and Pim-2, but not
      Pim-3, is dependent on Abl kinase activity. Transformation assays demonstrate
      that v-Abl cannot efficiently transform bone marrow cells derived from Pim-1(-/
      )/Pim-2(-/-) mice. Ectopic expression of either Pim-1 or Pim-2 in Pim-1(-/-)/Pim
      2(-/-) cells restores transformation by v-Abl, strongly suggesting that either
      Pim-1 or Pim-2 is required for v-Abl-mediated tumorigenesis. Interestingly, the
      combined deficiency of Pim-1, Pim-2, and Suppressor of Cytokine Signalling (SOCS)
      1 resulted in partial restoration of v-Abl transformation efficiency. In
      addition, Pim kinases are involved in modification of SOCS-1 and in regulating
      SOCS-1 protein levels in v-Abl-transformed cells. Furthermore, Pim kinases
      regulate the proapoptotic proteins Bcl-XS and BAD. Pim kinases inhibit the
      expression of Bcl-XS. Pim deficiency decreases the phosphorylation levels of BAD,
      whereas ectopic expression of Pim-1 increases the amount of phospho-BAD. This
      correlates with an increased protection from apoptosis in Abl transformants
      expressing Pim kinases. Together, these data suggest that Pim kinases play a key
      role in the v-Abl transformation, possibly via participating in modulation of
      SOCS-1 and via regulating the apoptotic signaling.

PMID- 18042806
TI  - Characterization of Vitis vinifera L. somatic variants exhibiting abnormal flower
      development patterns.
AB  - Mutants have proven to be a key resource for functional genomic studies in model
      annual plant species. In perennial plant species where mutants are difficult to
      generate and to screen, spontaneous somatic variants represent a unique resource
      to understand the genetic control of complex developmental patterns. The
      morphological and histological characterization of six Vitis vinifera L. somatic
      variants that display four different abnormal phenotypes of flower development
      are described here. A phenotype of reiterated reproductive meristems (RRM), with
      both flower and petal reiteration, was observed in a somatic variant of the
      cultivar Carignan. An abnormal development of reproductive organs was displayed
      by the unfused carpels (UFC) somatic variant of cv. Bouchales, while a somatic
      variant of cv. Mourvedre named carpel-less (CLS) developed abnormal ovules in the
      absence of carpels. Finally, three independent somatic variants in cvs Gamay,
      Morrastel, and Pinot displayed a phenotype of multiple perianth whorls (MPW).
      Gene expression studies showed that the expression profiles of VvMADS-box 1, 2,
      and 3 (putative orthologues of Arabidopsis flowering genes AG, SEP, and AGL13),
      were altered during grapevine flower development in the somatic variants, whereas
      the corresponding original cultivars displayed similar VvMADS-box gene expression
      profiles. Phenotypic and molecular characterization of these variants allowed the
      development of hypotheses on genetic functions that might be altered in most of
      the variants in light of the current ABCDE flower model.

PMID- 18042807
TI  - Exponential decay of GC content detected by strand-symmetric substitution rates
      influences the evolution of isochore structure.
AB  - The distribution of guanine and cytosine nucleotides throughout a genome, or the
      GC content, is associated with numerous features in mammals; understanding the
      pattern and evolutionary history of GC content is crucial to our efforts to
      annotate the genome. The local GC content is decaying toward an equilibrium
      point, but the causes and rates of this decay, as well as the value of the
      equilibrium point, remain topics of debate. By comparing the results of 2 methods
      for estimating local substitution rates, we identify 620 Mb of the human genome
      in which the rates of the various types of nucleotide substitutions are the same
      on both strands. These strand-symmetric regions show an exponential decay of
      local GC content at a pace determined by local substitution rates. DNA segments
      subjected to higher rates experience disproportionately accelerated decay and are
      AT rich, whereas segments subjected to lower rates decay more slowly and are GC
      rich. Although we are unable to draw any conclusions about causal factors, the
      results support the hypothesis proposed by Khelifi A, Meunier J, Duret L, and
      Mouchiroud D (2006. GC content evolution of the human and mouse genomes: insights
      from the study of processed pseudogenes in regions of different recombination
      rates. J Mol Evol. 62:745-752.) that the isochore structure has been reshaped
      over time. If rate variation were a determining factor, then the current isochore
      structure of mammalian genomes could result from the local differences in
      substitution rates. We predict that under current conditions strand-symmetric
      portions of the human genome will stabilize at an average GC content of 30%
      (considerably less than the current 42%), thus confirming that the human genome
      has not yet reached equilibrium.

PMID- 18042809
TI  - Publication records among college of pharmacy deans.

PMID- 18042808
TI  - Utilization of pharmacologic treatment in youths with attention
      deficit/hyperactivity disorder in Medicaid database.
AB  - BACKGROUND: Little is known about longitudinal changes in drug utilization in
      attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To describe
      longitudinal trends in ADHD drug utilization and explore demographic differences
      among youths eligible for a large Southern state Medicaid program. METHODS: A
      cross-sectional and longitudinal analysis of 10 years of claims data for all
      Medicaid beneficiaries younger than 20 years of age with 6 months or more of
      continuous insurance (N = 2,131,953) was conducted. Annual prevalence, incidence,
      and persistence in ADHD medication use (stimulants and atomoxetine) were
      estimated based on pharmacy claims and clinician-reported ADHD diagnosis.
      RESULTS: ADHD prevalence increased 1.70-fold (95% CI 1.67 to 1.73) from 3.10%
      (21,904 of 705,573 beneficiaries) in fiscal year 1995-1996 to 5.27% (41,681 of
      790,338) in 2003-2004, paralleled by a 1.84-fold (95% CI 1.81 to 1.87) increase
      in drug use to 4.63%. In 2003-2004, 0.89% of youths were diagnosed and newly
      started on drugs, reflecting a 1.38-fold (95% CI 1.33 to 1.43) increase over 1995
      1996. One in five white males between the ages of 10 and 14 years (19.24%; 95% CI
      18.81 to 19.67) received ADHD medication in 2003-2004. Males continued to be more
      likely diagnosed and treated than females (prevalence ratio [PR] in 2003-2004 =
      2.96; 95% CI 2.90 to 3.03 vs 3.82; 95% CI 3.69 to 3.96 in 1995-1996), as were
      whites when compared with Hispanics (PR in 2003-2004 = 2.65; 95% CI 2.57 to 2.73
      vs 3.78; 95% CI 3.57 to 3.99 in 1995-1996) and blacks (PR in 2003-2004 = 1.81;
      95% CI 1.76 to 1.85 vs 2.00; 95% CI 1.93 to 2.07 in 1995-1996). The most common
      starting age throughout the study period was 5-9 years, with 2.45% (95% CI 2.37
      to 2.52) new ADHD drug users in 2003-2004, but largest increases in prevalence
      were observed in adolescents 15-19 years of age, with 2.47% (95% CI 2.38 to 2.55)
      in 2003-2004 compared with 0.45% (95% CI 0.41 to 0.49) in 1995-1996. Medication
      persistence varied, with only 49.9% (95% CI 49.4 to 50.5) of new users receiving
      drugs after 1 year, with yet another 17.2% (95% CI 16.4 to 18.0) continuing for 5
      years or more. CONCLUSIONS: ADHD drug utilization continues to increase due to
      steady increases in diagnosis and chronic use of the drugs over several years.
      While racial, ethnic, and sex differences persist, the age distribution of drug
      users has shifted toward older children. These findings emphasize the need for
      studies that analyze determinants of treatment as well as outcomes, both benefits
      and risks, associated with long-term medication use.

PMID- 18042810
TI  - Safety of enoxaparin bridge therapy in patients with mechanical heart valves.

PMID- 18042811
TI  - Growth of protein, moisture, lipid, and ash of two genetic lines of barrows and
      gilts from twenty to one hundred twenty-five kilograms of body weight.
AB  - Two genetic lines of barrows and gilts with different lean growth rates were used
      to determine the BW and chemical composition growth from 23 to 125 kg of BW. The
      experiment was a 2 x 2 x 5 factorial arrangement of treatments in a completely
      randomized design conducted in 2 replicates. Six pigs from each sex and genetic
      line were killed at approximately 25-kg intervals from 23 kg to 125 kg of BW. At
      slaughter, tissues were collected and weighed. All components were ground and
      frozen until analyzed for water, protein, lipid, and ash. Serial BW data were
      fitted to alternative functions of day of age. Based on Akaike's information
      criteria values, the random effects model, BW(i, t) = (1 + c(i))(b(0) + b(1)t +
      b(2)t(2)), was the best mixed model equation. The chemical component mass data
      were fitted to alternative functions of BW. The allometric function, chemical
      component mass = aBW(b), provided the best fit to the data. Daily deposition
      rates of each chemical component were predicted by using the derivatives of the 2
      functions. The overall ADG of the 2 genetic lines were not different. Barrows had
      0.052 kg/d greater (P = 0.03) ADG than gilts. Allometric growth coefficients for
      all 4 chemical components were different (P < 0.01) for each genetic line.
      Allometric coefficients and predicted relative growth (g/kg of BW gain) for
      protein and moisture mass were greater (P < 0.01) for the high lean-gain pigs
      than the low lean-gain pigs. Allometric coefficients for lipid mass were smaller
      (P = 0.001) for the high lean-gain pigs than the low lean-gain pigs overall.
      Allometric coefficients and predicted relative growth rates for lipid mass were
      greater (P < 0.01) and for moisture and protein mass were lesser (P < 0.002) than
      the gilts. Compared with low lean-gain pigs, high lean-gain pigs had (1) 32.8%
      lesser predicted daily rates of lipid deposition (200 vs. 305 +/- 80 g/d), with
      the difference increasing from 23 to 37% from 25 to 125 kg of BW; (2) 12.3%
      greater daily rates of protein deposition (118.7 vs. 106.0 +/- 3.3 g/d); and (3)
      18.8% greater predicted daily moisture accretion rates (423 vs. 356 +/- 9 g/d).
      Overall, barrows had 21.3% greater lipid deposition (279 vs. 230 +/- 78.2 g/d)
      than gilts. In this study, barrows and gilts had similar predicted daily
      moisture, protein, and ash accretion rates.

PMID- 18042812
TI  - Board-invited review: Recent advances in biohydrogenation of unsaturated fatty
      acids within the rumen microbial ecosystem.
AB  - Recent advances in chromatographic identification of CLA isomers, combined with
      interest in their possible properties in promoting human health (e.g., cancer
      prevention, decreased atherosclerosis, improved immune response) and animal
      performance (e.g., body composition, regulation of milk fat synthesis, milk
      production), has renewed interest in biohydrogenation and its regulation in the
      rumen. Conventional pathways of biohydrogenation traditionally ignored minor
      fatty acid intermediates, which led to the persistence of oversimplified pathways
      over the decades. Recent work is now being directed toward accounting for all
      possible trans-18:1 and CLA products formed, including the discovery of novel
      bioactive intermediates. Modern microbial genetics and molecular phylogenetic
      techniques for identifying and classifying microorganisms by their small-subunit
      rRNA gene sequences have advanced knowledge of the role and contribution of
      specific microbial species in the process of biohydrogenation. With new insights
      into the pathways of biohydrogenation now available, several attempts have been
      made at modeling the pathway to predict ruminal flows of unsaturated fatty acids
      and biohydrogenation intermediates across a range of ruminal conditions. After a
      brief historical account of major past accomplishments documenting
      biohydrogenation, this review summarizes recent advances in 4 major areas of
      biohydrogenation: the microorganisms involved, identification of intermediates,
      the biochemistry of key enzymes, and the development and testing of mathematical
      models to predict biohydrogenation outcomes.

PMID- 18042813
TI  - Technical note: A novel technique to assess internal body fat of cattle by using
      real-time ultrasound.
AB  - The objectives of this study were to describe a system to assess KPH fat by using
      real-time ultrasound (RTU) and to develop equations to predict total physical
      separable internal fat (IFAT) based on ultrasound measurements. Data for this
      study were obtained from 24 Angus steers fed either hay- or corn-based diets
      during the backgrounding phase. Steers were serially slaughtered in 3 groups: at
      weaning (baseline), then at 4 and 8 mo after weaning. A fourth group was composed
      of 4 steers from the hay-fed group that were slaughtered at approximately 10 mo
      after weaning. The RTU measurements were collected every 2 mo, with a
      preslaughter scan approximately 7 d before the slaughter time. The RTU
      measurements consisted of 12th- to 13th-rib backfat thickness, 12th to 13th
      ribeye area, percentage of intramuscular fat, and kidney fat depth, which was
      measured in a cross-sectional image collected between the first lumbar vertebra
      and the 13th rib. For kidney fat, the ultrasound probe was placed on the flank
      region approximately 15 cm from the midline of the animal. Images were stored in
      the ultrasound console, and measurements were taken between the ventral part of
      the iliocostalis muscle and the end of the KPH fat at the chute side. The
      relationship between carcass and ultrasound measurements in the depths of kidney
      fat (cKFd and uKFd, respectively) had an r(2) of 0.93, with a root mean square
      error (RMSE) of 1.14 cm. An allometric regression between carcass KPH weight
      (cKPHwt) and cKFd was identified, and the untransformed regression had an r(2) of
      0.96. The linear regression between total IFAT and cKPHwt had an r(2) of 0.97,
      with an RMSE of 2.67 kg. Therefore, a system was developed to predict IFAT from
      uKFd measurements by combining these equations. Additionally, a single linear
      regression between IFAT and uKFd measurements was developed (r(2) = 0.89, RMSE =
      5.32 kg). Even though the system of equations had a lower RMSE of prediction and
      greater r(2) compared with the single linear regression (4.80 vs. 5.10 kg and
      0.91 vs. 0.89, respectively), there was no difference between these methods in
      predicting IFAT (P = 0.4936) by using a pairwise mean square error of prediction
      analysis. Our results indicated that uKFd measurements can accurately and
      precisely predict the cKFd of steers consuming either high concentrate or forage
      rations. The results also showed that cKFd is highly correlated with cKPHwt,
      which can be used to estimate total IFAT. More research is needed to further
      evaluate this technique with different feeding strategies, breeds, and sexes.

PMID- 18042814
TI  - Effects of supplementing fish oil in the drinking water of dairy cows on
      production performance and milk fatty acid composition.
AB  - The objective of this study was to determine the effects of supplementing fish
      oil (FO) in the drinking water of dairy cows on production performance and milk
      fatty acid composition. Sixteen multiparous Holstein dairy cows (741 +/- 84 kg of
      BW; 60 +/- 2.3 d in milk, mean +/- SD) housed in a tie-stall facility were used
      in the study. The study was conducted as a completely randomized design with
      repeated measurements. The cows were blocked by days in milk and allocated to 1
      of 2 treatments: 10 g of menhaden FO/kg of DM top-dressed on the total mixed
      ration (FOT), and 2 g of menhaden FO/L delivered in the drinking water (FOW). The
      trial lasted for 5 wk: a 1-wk pretreatment adjustment period and 4 wk of
      treatment. The animals were fed and milked twice daily (feeding at 0830 and 1300;
      milking at 0500 and 1500) and had unlimited access to water. Dry matter intake
      (21.3 kg/d for FOT vs. 22.7 +/- 0.74 kg/d for FOW), milk yield (38.2 kg/d for FOT
      vs. 39.5 +/- 1.9 kg/d for FOW), and water intake (101 L/d for FOT vs. 107 +/- 4.4
      L/d for FOW) were not affected by treatment. The mode of delivery of FO had no
      effect on milk fat percentage, but milk fat percentage declined linearly with
      time. The fatty acid contents of 7:0; 8:0; 9:0; 10:0; 12:0 in the milk of FOT
      cows were lower than for FOW cows, whereas 18:1 trans-12; 18:1 trans-13 and 14;
      18:1 trans-16; and trans-9, trans-11 plus trans-10, trans-12 CLA were greater for
      FOT than for FOW. The contents of 24:1 in the milk of FOW cows were 48% greater
      than for FOT cows, although the concentrations were low in both groups. There was
      a tendency for the contents of 14:0 and 22:5n-6 to be greater in FOW cows than
      FOT cows and for the contents of iso-18:0 to be lower for FOW cows than for FOT
      cows. Although it appears that the amount of FO added in the study did not bypass
      the rumen as hypothesized, these results suggest that drinking water can be an
      alternative for supplementing FO to dairy cows without decreasing feed or water
      intake relative to cows fed FO in the diet.

PMID- 18042815
TI  - Influence of processed grains on fecal pH, starch concentration, and shedding of
      Escherichia coli O157 in feedlot cattle.
AB  - Manipulation of cattle diets has been proposed as a possible preharvest control
      measure for Escherichia coli O157. Altering hindgut fermentation through diet
      changes may be a means to reduce fecal shedding of E. coli O157. In Exp. 1, the
      objective was to determine whether fecal shedding of E. coli O157 was related to
      fecal starch concentration. Beginning on d 20, and every week thereafter until d
      61, steers in 54 pens (6 to 7 steers per pen) were sampled (n = 122) by fecal
      collection and rectoanal mucosal swabs (RAMS) for E. coli O157 and fecal starch
      concentration determinations. Escherichia coli O157 prevalence was 3.3% in fecal
      samples, 4.1% as measured by RAMS, and 4.9% by fecal or RAMS samples. Steers
      positive for E. coli O157 contained 21% more (P < 0.05) fecal starch than steers
      that were negative for E. coli O157. In Exp. 2, we attempted to alter the
      concentration of starch escaping rumen fermentation by feeding finishing diets
      based on steam-flaked corn (SFC) and dry-rolled corn (DRC) to 30 heifers
      prescreened for being culture positive for fecal E. coli O157. Beginning on d 13,
      heifers were sampled (feces and RAMS) weekly to monitor fecal pH and starch
      concentration, and prevalence of E. coli O157. Prevalence of E. coli O157
      remained above 30% for the first 13 d, but declined (P < 0.05) over the entire 7
      wk period. Based on RAMS, the prevalence of E. coli O157 tended to be greater (P
      = 0.08) for heifers fed SFC than for those fed the DRC diet. After d 20, heifers
      fed DRC had greater (P < 0.05) fecal starch and lower (P < 0.05) fecal pH than
      heifers fed SFC. Fecal pH was negatively correlated (r = - 0.34; P < 0.05; n =
      143) with fecal starch concentration. Fecal starch concentration and pH were not
      different (P > 0.05) for heifers that were positive or negative for E. coli O157.
      Our data suggest that fecal shedding of E. coli O157 was not related to fecal pH
      or starch concentration in cattle fed grain-based diets.

PMID- 18042816
TI  - In vitro methane emission and acetate:propionate ratio are decreased when
      artificial stimulation of the rumen wall is combined with increasing grain diets
      in sheep.
AB  - The interaction of retention time in the rumen and concentrate diet on methane
      production in vitro and acetate:propionate ratio was examined. Twenty-four
      fistulated sheep were used in a complete factorial design with the sheep randomly
      divided into 4 groups. The sheep had a 5-wk acclimatization period on an oaten
      chaff diet, followed by two 3-wk diet phases. Two of the 4 groups were maintained
      on the oaten chaff diet for the duration of the experiment, with pot scrubbers
      added to the rumen of 1 of the 2 groups. The remaining 2 groups were offered a
      low-grain diet (35% grain) in the first diet phase followed by a high-grain diet
      (70% grain) in the second diet phase. Pot scrubbers were also added to the rumen
      of 1 of these 2 groups of grain-fed sheep. Pot scrubbers in combination with a
      low-grain diet decreased the amount of methane produced in vitro from 4.25 to
      3.71 mmol/mL of digesta when compared with oaten chaff-fed sheep without pot
      scrubbers (P < 0.05). The acetate:propionate ratio was 1.6 in sheep fed a high
      grain diet with pot scrubbers compared with 2.4 in sheep fed a high-grain diet
      without pot scrubbers in their rumen (P < 0.05). At high levels of grain, when
      employing a multivariate statistical analysis including all data, sheep given the
      combined treatment of grain and pot scrubbers were different from all other sheep
      groups in this experiment (P < 0.05). Furthermore, sheep fed a high-grain diet
      were different from sheep receiving the oaten chaff diets with and without pot
      scrubbers (P < 0.01 and P < 0.05, respectively). In conclusion, pot scrubbers
      combined with grain alter the rumen fermentation, and introducing pot scrubbers
      into the rumens of livestock consuming low levels of grain may be a way to lower
      methane emissions.

PMID- 18042817
TI  - Effects of increasing dose of live cultures of Lactobacillus acidophilus (Strain
      NP 51) combined with a single dose of Propionibacterium freudenreichii (Strain NP
      24) on performance and carcass characteristics of finishing beef steers.
AB  - Two experiments, each with a randomized complete block design, were conducted to
      evaluate the effects of feeding live cultures of Lactobacillus acidophilus plus
      Propionibacterium freudenreichii on performance and carcass characteristics of
      feedlot cattle. British and British x Continental steers (240 steers in each
      experiment; 12 pens/treatment in each study; average initial BW = 370 +/- 6 kg)
      were fed a 92% concentrate diet based primarily on steam-flaked corn. Four
      treatments were evaluated, which included a control diet (lactose carrier only)
      or diets containing 1 x 10(9) cfu/(steer x d) of P. freudenreichii (strain NP 24)
      with 1 x 10(7) (L), 1 x 10(8) (M), or 1 x 10(9) (H) cfu of L. acidophilus strain
      NP 51/(steer x d). Data were pooled for the 2 experiments. No differences (P >
      0.10) were detected among treatments for final BW, final BW based on HCW, or DMI
      during various stages of the feeding period or overall. Likewise, no differences
      among treatments were observed for either ADG or carcass-adjusted ADG (P > 0.10),
      except for the tendency for a quadratic effect of NP 51 dose for the overall
      feeding period (P = 0.10), in which cattle fed M had a lower ADG than those fed L
      and H. Gain efficiency on a live BW basis was improved (P = 0.02) by NP 51
      treatments compared with the control, with G:F responding quadratically to NP 51
      dose for the overall feeding period (P = 0.05). In contrast to G:F based on live
      BW, carcass-adjusted G:F tended (P = 0.14) to decrease linearly with increasing
      NP 51 dose because the dressing percent tended (P = 0.12) to be less for steers
      fed direct-fed microbial compared with control cattle. Within the direct-fed
      microbial treatments, there also was a tendency (P = 0.13) for a linear decrease
      in the dressing percent as the NP 51 dose increased. No differences were observed
      in other carcass characteristics (P > 0.10), except tendencies for a quadratic
      increase in marbling score (P = 0.11) and percentage of USDA Choice cattle (P =
      0.10). These data indicate that live cultures of L. acidophilus strain NP 51 plus
      P. freudenreichii strain NP 24 increased G:F of feedlot cattle fed steam-flaked
      corn-based diets by approximately 2%, but the effects depended on the dose of
      Lactobacillus.

PMID- 18042818
TI  - Combined inhaled diesel exhaust particles and allergen exposure alter methylation
      of T helper genes and IgE production in vivo.
AB  - Changes in methylation of CpG sites at the interleukin (IL)-4 and interferon
      (IFN)-gamma promoters are associated with T helper (Th) 2 polarization in vitro.
      No previous studies have examined whether air pollution or allergen exposure
      alters methylation of these two genes in vivo. We hypothesized that diesel
      exhaust particles (DEP) would induce hypermethylation of the IFN-gamma promoter
      and hypomethylation of IL-4 in CD4+ T cells among mice sensitized to the fungus
      allergen Aspergillus fumigatus. We also hypothesized that DEP-induced methylation
      changes would affect immunoglobulin (Ig) E regulation. BALB/c mice were exposed
      to a 3-week course of inhaled DEP exposure while undergoing intranasal
      sensitization to A. fumigatus. Purified DNA from splenic CD4+ cells underwent
      bisulfite treatment, PCR amplification, and pyrosequencing. Sera IgE levels were
      compared with methylation levels at several CpG sites in the IL-4 and IFN-gamma
      promoter. Total IgE production was increased following intranasal sensitization
      A. fumigatus. IgE production was augmented further following combined exposure to
      A. fumigatus and DEP exposure. Inhaled DEP exposure and intranasal A. fumigatus
      induced hypermethylation at CpG(-45), CpG(-53), CpG(-205) sites of the IFN-gamma
      promoter and hypomethylation at CpG(-408) of the IL-4 promoter. Altered
      methylation of promoters of both genes was correlated significantly with changes
      in IgE levels. This study is the first to demonstrate that inhaled environmental
      exposures influence methylation of Th genes in vivo, supporting a new paradigm in
      asthma pathogenesis.

PMID- 18042819
TI  - Comparative toxicogenomic examination of the hepatic effects of PCB126 and TCDD
      in immature, ovariectomized C57BL/6 mice.
AB  - Polychlorinated biphenyls are persistent environmental pollutants that elicit a
      wide range of effects in humans and wildlife, mediated by the aryl hydrocarbon
      receptor. 3,3',4,4',5-pentachlorobiphenyl (PCB126) is the most potent congener
      with relative effect potencies ranging from 0.0026 to 0.857, and a toxic
      equivalency factor (TEF) of 0.1 set by an expert panel of the World Health
      Organization. In this study, the hepatic effects elicited by 300 microg/kg PCB126
      were compared with 30 microg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in
      immature, ovariectomized female C57BL/6 mice. Comprehensive hepatic gene
      expression analyses with complementary histopathology, high-resolution gas
      chromatograph/high-resolution mass spectrometer tissue analysis, and clinical
      chemistry were examined. For temporal analysis, mice were orally gavaged with
      PCB126 or sesame oil vehicle and sacrificed after 2, 4, 8, 12, 18, 24, 72, 120,
      or 168 h. In the dose-response study, mice were gavaged with 0.3, 1, 3, 10, 30,
      100, 300, 1000 microg/kg PCB126, 30 or 100 microg/kg TCDD and sacrificed after 72
      h. 251 and 367 genes were differentially expressed by PCB126 at one or more time
      points or doses, respectively, significantly less than elicited by TCDD. In
      addition, there was less vacuolization and necrosis, and no immune cell
      infiltration, despite comparable or higher TEF-adjusted hepatic PCB126 levels.
      The functional annotation of differentially expressed genes was consistent with
      the observed histopathology. Collectively, the data indicate that 300 microg/kg
      PCB126 elicited a subset of weaker effects compared with 30 microg/kg TCDD in
      immature, ovariectomized C57BL/6 mice.

PMID- 18042820
TI  - Award winning papers. So what?

PMID- 18042821
TI  - A preliminary report of a new design of cast metal fixed twin-block appliance.
AB  - The present paper describes a cast metal fixed twin-block appliance utilized to
      correct a Class II malocclusion, which is designed for full-time wear. The object
      of the present paper is to achieve rapid functional correction of Class II
      malocclusions by transmitting favourable occlusal forces to inclined planes which
      are cemented to the posterior teeth. In the meantime, pre-adjusted fixed edgewise
      appliances can be placed on the anterior teeth to correct their malpositions.
      This new functional appliance design may shorten the total treatment duration and
      reduce the need for patient compliance.

PMID- 18042822
TI  - Orthodontic treatment of a patient with a renal transplant and drug-induced
      gingival overgrowth: a case report.
AB  - The treatment of transplant patients is becoming an ever-increasing part of
      modern-day orthodontic practice. This report details the successful orthodontic
      management of a paediatric renal transplant patient with significant drug-induced
      gingival overgrowth. The problems that such patients present with are discussed
      before considering the specific orthodontic techniques employed. Recommendations
      are made for practitioners managing such cases.

PMID- 18042823
TI  - The Quatro appliance: a removable aligner with a changeable labial bow.
AB  - Lower labial segment irregularity is a feature that is presenting more frequently
      as greater emphasis is placed on aesthetics than ever before. The authors report
      on a removable appliance that is easy to construct and use and is designed to
      deal with mild labial tooth irregularity. In cases of crowding the aligner can be
      used in conjunction with inter-proximal stripping. The device incorporates a
      removable labial bow attached bilaterally to a sliding lock. This lock permits
      the addition of sectional archwires to the labial part of the appliance. The
      versatility of the aligner allows round and rectangular wires of different
      materials and dimensions to be placed with or without bends.

PMID- 18042824
TI  - Tooth-size discrepancy and Bolton's ratios: the reproducibility and speed of two
      methods of measurement.
AB  - OBJECTIVE: To determine and compare the reproducibility and speed of two methods
      of performing Bolton's tooth-size analysis. DESIGN: Analysis of randomly selected
      clinical sample. SETTING: Bristol Dental Hospital, University of Bristol, United
      Kingdom. MATERIALS AND METHODS: Pre-treatment study casts of 150 patients were
      selected randomly from 1100 consecutively treated Caucasian orthodontic patients.
      Bolton tooth-size discrepancies and ratios were measured using two methods; one
      method employed entirely manual measurement and the Odontorule slide rule, while
      the other employed digital calipers and the HATS analysis software. Twenty study
      casts were measured twice, a week apart with both methods. Another three
      investigators also measured 20 study casts twice with the HATS analysis. RESULTS:
      There were small or no systematic errors within or between these two methods. A
      very significant difference was evident for mean time measurements between the
      two methods (mean time for HATS was 3.5 minutes and for Odontorule was 8.9
      minutes). There was relatively high error variance of both methods of measurement
      as a percentage of the total variance. CONCLUSIONS: On-line electronic
      measurement was found to be more rapid than the manual method used. Both methods
      demonstrate relatively high random error and this has important consequences for
      the clinical use of Bolton's ratios.

PMID- 18042826
TI  - How to ... manage the transition from functional to fixed appliances.
AB  - This paper presents the methods of transfer from functional to fixed appliances.
      The aim of transition should be maintenance of Class II correction in a time
      efficient manner without compromising long-term patient co-operation.

PMID- 18042825
TI  - Long-term clinical evaluation of bracket failure with a self-etching primer: a
      randomized controlled trial.
AB  - OBJECTIVE: A long-term comparison of the failure rates of orthodontic brackets
      bonded with either a self-etching primer (SEP) or conventional etch and primer
      (AE). DESIGN: Prospective randomized controlled clinical trial. SETTING: UK
      district general hospital with one operator, 2003-6. PARTICIPANTS: Hospital
      waiting list patients needing fixed appliances (n=60). METHOD: Experimental (SEP)
      group patients (n=30) received pre-adjusted edgewise brackets (n=438) bonded with
      Transbond Plus following manufacturer's instructions. Control (AE) group patients
      (n=30, brackets n=433) were bonded using a 15-second conventional etch and primer
      (Transbond XT). In both groups brackets were light-cured for 20 seconds. First
      time bond failures were recorded with the time of failure. Bracket bonding time
      was recorded. All patients were followed to the end or discontinuation of
      treatment. RESULTS: Bracket failure rates: SEP=4.8%, AE=3.5%, P=0.793. Mean
      placement time per bracket (seconds): SEP=75.5 (+/-6.7; 95% CI=72.9, 78.0),
      AE=97.7 (+/-9.1; 95% CI=94.3, 101.2) P=0.000. CONCLUSION: There was no difference
      in the failure rates of brackets bonded with either Transbond Plus SEP or
      conventional AE using Transbond XT paste. Bonding with SEP was significantly
      faster than using conventional AE.

PMID- 18042827
TI  - Ceramide: a key signaling molecule in a Guinea pig model of allergic asthmatic
      response and airway inflammation.
AB  - Although mechanisms involved in the pathogenesis of asthma remain unclear, roles
      for oxidative/nitrosative stress, epithelial cell apoptosis, and airway
      inflammation have been documented. Ceramide is a sphingolipid with potent
      proinflammatory and proapoptotic properties. This study aimed at determining
      whether increased formation of ceramide contributes to the development of airway
      inflammation and hyper-responsiveness, using a well characterized in vivo model
      of allergic asthmatic response and airway inflammation in ovalbumin-sensitized
      guinea pigs. Aerosol administration of ovalbumin increased ceramide levels and
      ceramide synthase activity in the airway epithelium associated with respiratory
      abnormalities, such as cough, dyspnea, and severe bronchoconstriction. These
      abnormalities correlated with nitrotyrosine formation in the airway epithelium
      and oxidative/nitrosative stress, epithelial cell apoptosis, and airway
      inflammation evident by the infiltration of neutrophils and eosinophils in lung
      tissues, mast cell degranulation, and release of prostaglandin D(2) and
      proinflammatory cytokines. Inhibition of de novo ceramide synthesis with the
      competitive and reversible inhibitor of ceramide synthase fumonisin B1 (0.25, 0.5
      and 1 mg/kg b.wt.), given i.p. daily for 4 days before allergen challenge,
      attenuated nitrotyrosine formation and oxidative/nitrosative stress, epithelial
      cell apoptosis, and airway inflammation while improving the respiratory and
      histopathological abnormalities. These results implicate ceramide in the
      development of allergic asthmatic response and airway inflammation. Strategies
      aimed at reducing the levels of ceramide and downstream events should yield
      promising novel anti-asthmatic agents.

PMID- 18042828
TI  - Expression and functionality of anti-human immunodeficiency virus and anticancer
      drug uptake transporters in immune cells.
AB  - Almost all drugs used in anti-human immunodeficiency virus (HIV)-1 and anticancer
      therapies require membrane proteins to get into the cell to develop their proper
      activity. Nevertheless, little is known regarding the expression and activity of
      specific carriers involved in the uptake of these drugs in immune cells. Here, we
      assessed the mRNA levels, protein expression profile, and activity of the gene
      families SLC28 (coding for concentrative nucleoside transporters, hCNT1-3), SLC29
      (equilibrative nucleoside transporters, hENT1-2), and SLC22 (organic cation
      transporters, hOCT1-3 and hOCTN1-2). Both hENTs and hCNT2 were abundant in
      primary lymphocytes, with a preferential activity of hENT1. A significant up
      regulation in hENTs expression (100-fold) and activity (30-fold) was seen under
      stimulation of primary T lymphocytes. In contrast, monocytes, monocyte-derived
      macrophages (MDMs), and immature monocyte-derived dendritic cells predominantly
      expressed hCNT3, a functional transporter in MDMs. Finally, in immune cells,
      hOCTs showed a more heterogeneous expression profile and a lower activity than
      human nucleoside transporters (hNTs), although up-regulation of hOCTs also
      occurred upon lymphocyte activation. Overall, the expression and activity of most
      of the studied transporters emphasize their relevance in relation to anti-HIV and
      anticancer therapies. The identification of the transporter involved in each
      specific drug uptake in immune cells could help to optimize pharmacological
      therapeutic responses.

PMID- 18042829
TI  - Anti-inflammatory and cardioprotective activities of synthetic high-density
      lipoprotein containing apolipoprotein A-I mimetic peptides.
AB  - Apolipoprotein A-I (apoA-I) mimetic peptides may represent an alternative to apoA
      I for large-scale production of synthetic high-density lipoproteins (sHDL) as a
      therapeutic agent. In this study, the cardioprotective activity of sHDL made with
      either L37pA peptide or its d-stereoisomer, D37pA, was compared to sHDL made with
      apoA-I. The peptides were reconstituted with palmitoyl-oleoyl
      phosphatidylcholine, which yielded sHDL particles comparable to apoA-I sHDL in
      diameter, molecular weight, and alpha-helical content. Pretreatment of
      endothelial cells with either peptide sHDL reduced tumor necrosis factor alpha
      stimulated vascular cell adhesion molecule-1 expression to the same extent as
      apoA-I sHDL. In an isolated rat heart model of ischemia/reperfusion (I/R) injury,
      L37pA and D37pA sHDL significantly reduced postischemic cardiac contractile
      dysfunction compared to the saline control, as indicated by a 49.7 +/- 6.4%
      (L37pA; P < 0.001) and 53.0 +/- 9.1% (D37pA; P < 0.001) increase of left
      ventricular-developed pressure (LVDP) after reperfusion and by a 45.4 +/- 3.4%
      (L37pA; P < 0.001) and 49.6 +/- 2.6% (D37pA; P < 0.001) decrease of creatine
      kinase (CK) release. These effects were similar to the 51.3 +/- 3.0% (P < 0.001)
      increase of LVDP and 51.3 +/- 3.0 (P < 0.001) reduction of CK release induced by
      apoA-I sHDL. Consistent with their cardioprotective effects, all three types of
      sHDL particles mediated an approximate 20% (P < 0.001) reduction of cardiac tumor
      necrosis factor alpha (TNFalpha) content and stimulated an approximate 35% (P <
      0.05) increase in postischemic release of prostacyclin. In summary, L37pA and
      D37pA peptides can form sHDL particles that retain a similar level of protective
      activity as apoA-I sHDL on the endothelium and the heart; thus, apoA-I mimetic
      peptides may be useful therapeutic agents for the prevention of cardiac I/R
      injury.

PMID- 18042830
TI  - Painful purinergic receptors.
AB  - Multiple P2 receptor-mediated mechanisms exist by which ATP can alter nociceptive
      sensitivity following tissue injury. Evidence from a variety of experimental
      strategies, including genetic disruption studies and the development of selective
      antagonists, has indicated that the activation of P2X receptor subtypes,
      including P2X(3), P2X(2/3), P2X(4) and P2X(7), and P2Y (e.g., P2Y(2)) receptors,
      can modulate pain. For example, administration of a selective P2X(3) antagonist,
      A-317491, has been shown to effectively block both hyperalgesia and allodynia in
      different animal models of pathological pain. Intrathecally delivered antisense
      oligonucleotides targeting P2X(4) receptors decrease tactile allodynia following
      nerve injury. Selective antagonists for the P2X(7) receptor also reduce
      sensitization in animal models of inflammatory and neuropathic pain, providing
      evidence that purinergic glial-neural interactions are important modulators of
      noxious sensory neurotransmission. Furthermore, activation of P2Y(2) receptors
      leads to sensitization of polymodal transient receptor potential-1 receptors.
      Thus, ATP acting at multiple purinergic receptors, either directly on neurons
      (e.g., P2X(3), P2X(2/3), and P2Y receptors) or indirectly through neural-glial
      cell interactions (P2X(4) and P2X(7) receptors), alters nociceptive sensitivity.
      The development of selective antagonists for some of these P2 receptors has
      greatly aided investigations into the nociceptive role of ATP. This perspective
      highlights some of the recent advances to identify selective P2 receptor ligands,
      which has enhanced the investigation of ATP-related modulation of pain
      sensitivity.

PMID- 18042831
TI  - Short-term high fat-feeding results in morphological and metabolic adaptations in
      the skeletal muscle of C57BL/6J mice.
AB  - The prevalence of the metabolic syndrome (MS) is rapidly increasing all over the
      world. Consequently, there is an urgent need for more effective intervention
      strategies. Both animal and human studies indicate that lipid oversupply to
      skeletal muscle can result in insulin resistance, which is one of the
      characteristics of the MS. C57BL/6J mice were fed a low-fat (10 kcal%) palm oil
      diet or a high-fat (45 kcal%; HF) palm oil diet for 3 or 28 days. By combining
      transcriptomics with protein and lipid analyses we aimed to better understand the
      molecular events underlying the early onset of the MS. Short-term HF feeding led
      to altered expression levels of genes involved in a variety of biological
      processes including morphogenesis, energy metabolism, lipogenesis, and immune
      function. Protein analysis showed increased levels of the myosin heavy chain,
      slow fiber type protein, and the complexes I, II, III, IV, and V of the oxidative
      phosphorylation. Furthermore, we observed that the main mitochondrial membrane
      phospholipids, phosphatidylcholine and phosphatidylethanolamine, contained more
      saturated fatty acids. Altogether, these results point to a morphological as well
      as a metabolic adaptation by promoting a more oxidative fiber type. We
      hypothesize that after this early positive adaptation, a continued
      transcriptional downregulation of genes involved in oxidative phosphorylation
      will result in decreased oxidative capacity at a later stage. Together with
      increased saturation of phospholipids of the mitochondrial membrane this can
      result in decreased mitochondrial function, which is a hallmark observed in
      insulin resistance and Type 2 diabetes.

PMID- 18042832
TI  - Dissociation of obesity and insulin resistance in transgenic mice with skeletal
      muscle expression of uncoupling protein 1.
AB  - We evaluated the effect of skeletal muscle mitochondrial uncoupling on energy and
      glucose metabolism under different diets. For 3 mo, transgenic HSA-mUCP1 mice
      with ectopic expression of uncoupling protein 1 in skeletal muscle and wild-type
      littermates were fed semisynthetic diets with varying macronutrient ratios
      (energy % carbohydrate-protein-fat): HCLF (41:42:17), HCHF (41:16:43); LCHF
      (11:45:44). Body composition, energy metabolism, and insulin resistance were
      assessed by NMR, indirect calorimetry, and insulin tolerance test, respectively.
      Gene expression in different organs was determined by real-time PCR. In wild
      type, both high-fat diets led to an increase in body weight and fat. HSA-mUCP1
      mice considerably increased body fat on HCHF but stayed lean on the other diets.
      Irrespective of differences in body fat content, HSA-mUCP1 mice showed higher
      insulin sensitivity and decreased plasma insulin and liver triglycerides.
      Respiratory quotient and gene expression indicated overall increased carbohydrate
      oxidation of HSA-mUCP1 but a preferential channeling of fatty acids into muscle
      rather than liver with high-fat diets. Evidence for increased lipogenesis in
      white fat of HSA-mUCP1 mice suggests increased energy dissipating substrate
      cycling. Retinol binding protein 4 expression in white fat was increased in HSA
      mUCP1 mice despite increased insulin sensitivity, excluding a causal role in the
      development of insulin resistance. We conclude that skeletal muscle mitochondrial
      uncoupling does not protect from the development of obesity in all circumstances.
      Rather it can lead to a "healthy" obese phenotype by preserving insulin
      sensitivity and a high metabolic flexibility, thus protecting from the
      development of obesity associated disturbances of glucose homeostasis.

PMID- 18042833
TI  - Evaluation of LEXF/FXLE rat recombinant inbred strains for genetic dissection of
      complex traits.
AB  - Recombinant inbred (RI) strains are formed from an outcross between two well
      characterized inbred stains followed by at least 20 generations of inbreeding. RI
      strains can be utilized for the analysis of many complex phenotypic traits. The
      LEXF/FXLE RI strain set consists of 34 RI strains derived by reciprocal crossing
      of LE/Stm and F344/Stm. Here we report on genetic dissections of complex traits
      using this RI set and their parental strains. We have developed strain
      distribution patterns for 232 informative simple sequence length polymorphism
      markers. The framework map covers the rat genome except for chromosome Y. Seventy
      six phenotype parameters, which included physiological and behavioral traits,
      were examined for these RI lines. Quantitative trait locus (QTL) analysis of
      these parameters revealed 27 significant and 91 suggestive QTLs, illustrating the
      potential of this RI resource for the detection of underlying gene functions for
      various phenotypes. Although this RI set was originally developed to study
      susceptibility to chemical-induced tumors, it has been shown to be equally
      powerful for a wide spectrum of traits. The LEXF/FXLE RI strains have been
      deposited at the National Bio Resource Project for the Rat in Japan and are
      maintained under specific pathogen-free conditions. They are available at
      http://www.anim.med.kyoto-u.ac.jp/nbr.

PMID- 18042834
TI  - Treatment outcome and survival in participants of phase I oncology trials carried
      out from 2003 to 2006 at Institut Gustave Roussy.
AB  - BACKGROUND: The oncology community usually perceives phase I oncology trials as
      associated with poor or limited benefits and substantial risks. There is scarce
      data concerning outcome and survival of patients enrolled in current phase I
      oncology trials. PATIENTS AND METHODS: We reviewed all phase I oncology trials
      conducted by investigators from the Adult Phase I Unit at Institut Gustave Roussy
      from 2003 to 2006. We report data concerning patient demographics, treatment
      outcome, toxicity, survival and type of care after trial exit. RESULTS: We
      analyzed 10 trials involving 180 participants. The overall response rate was
      7.2%. Disease control (objective response plus stable disease) was achieved in
      48.2% of patients. The rate of toxic death was 0.5%. In all, 38% of patients had
      at least one episode of grade 3 or 4 toxic events. The median progression-free
      survival and the median overall survival (OS) were 2.3 and 8.7 months,
      respectively. On multivariate analysis, a time between diagnosis of disease and
      inclusion in the phase I trial > or =24 months and evidence of disease control
      were statistically significant predictors of improved OS. CONCLUSION: Current
      phase I oncology trials are safe and are associated with clinical benefit in a
      substantial proportion of patients.

PMID- 18042835
TI  - Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and
      CMF in patients with high-risk breast cancer: safety analysis of the Hellenic
      Cooperative Oncology Group randomized phase III trial HE 10/00.
AB  - BACKGROUND: A randomized phase III trial in high-risk breast cancer patients was
      conducted, to further explore the impact of dose-density in the adjuvant
      treatment for breast cancer. The safety analysis is presented. PATIENTS AND
      METHODS: From October 2000 until June 2005, 1121 node-positive patients were
      randomized to sequential dose-dense epirubicin 110 mg/m(2) and paclitaxel (Taxol,
      Bristol Myers-Squibb, Princeton, New Jersey, USA) 250 mg/m(2) (group A), or
      concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both
      followed by three cycles of 'intensified' combination chemotherapy with
      cyclophosphamide, methotrexate and fluorouracil (CMF). Granulocyte colony
      stimulating factor was given prophylactically with the dose-dense treatments.
      RESULTS: Median dose intensity of epirubicin and paclitaxel was double in group
      A, as designed, with significantly less cycles administered at full dose (P <
      0.001). Median cumulative dose of all drugs and total treatment duration,
      however, were identical between groups. Severe taxane-related toxic effects were
      more frequent in group A, while severe thrombocytopenia was low and present only
      in group A. There were no differences in the rates of other hematological toxic
      effects, including febrile neutropenia. The rates of secondary malignancies were
      low. CONCLUSION: Both regimens as used in the present study are well tolerated
      and safe. The rates of severe taxane-related toxic effects and thrombocytopenia,
      although low overall, are significantly increased with the dose-dense sequential
      regimen.

PMID- 18042836
TI  - Proliferation accurately identifies the high-risk patients among small, low
      grade, lymph node-negative invasive breast cancers.
AB  - BACKGROUND: The proliferation factor mitotic activity index (MAI) is the
      strongest prognosticator in lymph node-negative invasive breast cancer patients
      under age 71. The question remains, whether this also holds for 'favourable
      prognosis' subgroups. PATIENTS AND METHODS: The study was a multicentre
      prospective analysis of the MAI for recurrence-free survival and overall cancer
      related survival of grade, MAI, and other prognosticators in 853 long-term follow
      up, T1-3N0M0 breast cancer patients under 71 years. RESULTS: In all tumours
      together (N = 853), in grade 3 (n = 269), in tumours <1 cm all grades (n = 84), 1
      2 cm, grades 1 + 2 (n = 300), and 2-3 cm, grades 1 + 2 (n = 124), the MAI is
      prognostically superior. Other features [grade, estrogen receptor (ER), diameter,
      and age] did not enhance its prognostic value except in grades 1 + 2 tumours 2-3
      cm diameter with MAI <10, where ER has an additional prognostic value.
      CONCLUSIONS: In women <71 years with T1-3N0M0 small or low-grade invasive breast
      cancer usually not receiving systemic treatment, MAI > or =10 accurately
      identifies those at high risk. These high-risk patients should be considered for
      adjuvant systemic therapy.

PMID- 18042837
TI  - Gastric extranodal marginal zone B-cell lymphomas of MALT type exclusively
      express Toll-like receptor 4 in contrast to other lymphomas infiltrating the
      stomach.
AB  - BACKGROUND: Development and growth of extranodal marginal zone B-cell lymphomas
      (eMZBCLs) of mucosa-associated lymphoid tissue (MALT) type are thought to be
      highly dependent on Helicobacter pylori and autoantigens. Receptors mediating
      these effects are not characterised so far. Toll-like receptors (TLRs) recognise
      bacterial proteins and autoantigens, which results in inflammatory reactions and
      influences tumour development and growth. MATERIALS AND METHODS: TLR4, 5 and 9
      expressions were evaluated by immunohistology and confocal microscopy in gastric
      eMZBCL in comparison to other lymphomas infiltrating the stomach. RESULTS: TLR4
      was exclusively expressed on the cell surface in all eMZBCL (n = 19) and not in
      chronic lymphocytic leukaemia (CLL, n = 12) or mantle cell lymphoma (MCL, n =
      10). TLR5 was strongly expressed in CLL and weak in some eMZBCL (15 of 19), but
      not in MCL. TLR4, 5 and 9 were negative in all the three lymphoma entities.
      CONCLUSIONS: Exclusive TLR4 expression may enable eMZBCL to interact with H.
      pylori and autoantigens. Blockade of TLR4 might be a new approach for therapy of
      eMZBCL of MALT type.

PMID- 18042838
TI  - Assessing prognosis and optimizing treatment in patients with postchemotherapy
      viable nonseminomatous germ-cell tumors (NSGCT): results of the sCR2
      international study.
AB  - BACKGROUND: The purpose of this study was to validate a prognostic index
      [surgical complete response 1 (sCR1)] in patients with postchemotherapy viable
      nonseminomatous germ-cell tumors (NSGCT). PATIENTS AND METHODS: Data and
      specimens from 61 patients with normalized tumor markers and postchemotherapy
      viable nonteratomatous NSGCT treated in 13 institutions were collected. RESULTS:
      With a median follow-up of 5.4 years, the 5-year progression-free survival (PFS)
      rate was 65%; the 5-year overall survival (OS) rate was 72%. Favorable PFS was
      predicted by a complete resection, <10% of viable malignant cells, and a good
      International Germ Cell Consensus Classification group at presentation. Patients
      were assigned to one of three risk groups defined in sCR1: no risk factor (good
      risk), one risk factor (intermediate risk) and two to three risk factors (poor
      risk group). The 5-year PFS rate was 92%, 78%, and 42%, respectively (P = 0.002)
      (as compared with 90%, 76%, and 41% in the original sCR1 study). The 5-year OS
      rate was 90%, 86%, and 52%, respectively (P = 0.009) (as compared with 100%, 83%,
      and 51% in the original sCR1 study). Postoperative chemotherapy did not appear to
      improve OS compared with surveillance and treatment only at relapse. CONCLUSION:
      In patients with postchemotherapy viable NSGCT, a complete resection of residual
      masses should be rigorously pursued. These data validate the sCR1 prognostic
      index. Given their excellent outcome, patients in the favorable group may not
      require postoperative chemotherapy.

PMID- 18042839
TI  - General parenting, anti-smoking socialization and smoking onset.
AB  - A theoretical model was tested in which general parenting and parental smoking
      predicted anti-smoking socialization, which in turn predicted adolescent smoking
      onset. Participants were 4351 Dutch adolescents between 13 and 15 years of age.
      In the model, strictness and psychological autonomy granting were related to
      lower likelihood of smoking onset, and parental smoking was positively related to
      smoking onset. Involvement and strictness were positively related to anti-smoking
      socialization, whereas parents who smoke where less likely to be engaged in anti
      smoking socialization. In turn, anti-smoking socialization was negatively related
      to adolescent smoking. To test mediation, an asymptotic resampling method was
      used (bootstrapping); anti-smoking socialization appeared to mediate the links
      between involvement and smoking onset, strictness and smoking onset and parental
      smoking and smoking onset. In addition, parental smoking appeared to moderate the
      link between anti-smoking socialization and smoking onset. Implications for
      prevention were addressed.

PMID- 18042840
TI  - Studies on diagnostic injections and surgery for low back pain: problems,
      advances, and opportunities.

PMID- 18042841
TI  - Will seeing become believing?

PMID- 18042842
TI  - Practice guidelines for the management of postoperative nausea and vomiting:
      past, present, and future.

PMID- 18042843
TI  - The use of compact ultrasound in anesthesia: friend or foe.

PMID- 18042844
TI  - Reactive oxygen species mediate sevoflurane- and desflurane-induced
      preconditioning in isolated human right atria in vitro.
AB  - BACKGROUND: We examined the role of reactive oxygen species (ROS) in sevoflurane-
      and desflurane-induced preconditioning on isolated human right atrial myocardium.
      METHODS: We recorded isometric contraction of human right atrial trabeculae
      suspended in an oxygenated Tyrode's solution (34 degrees C, stimulation frequency
      1 Hz). In all groups, a 30-min hypoxic period was followed by 60 min of
      reoxygenation. Ten minutes before hypoxia reoxygenation, muscles were exposed to
      5 min of sevoflurane 2% or desflurane 6%. In separate groups, the sevoflurane 2%
      (Sevo + N-(2-mercaptopropionyl)-glycine [MPG]) or desflurane 6% (Des + MPG) was
      administered in the presence of 0.1 mM MPG, a ROS scavenger. The effect of 0.1 mM
      MPG alone was tested. Recovery of force after a 60-min reoxygenation period was
      compared between groups (mean +/- sd). RESULTS: Preconditioning with sevoflurane
      2% (85% +/- 4% of baseline) or desflurane 6% (86% +/- 7% of baseline) enhanced
      the recovery of the force of myocardial contraction after 60 min reoxygenation
      compared with the control group (53% +/- 11% of baseline, P < 0.001). This effect
      was abolished in the presence of MPG (56% +/- 12% of baseline for Sevo + MPG, 48%
      +/- 13% of baseline for Des + MPG). The effect of MPG alone on the recovery of
      force was not different from the control group (57% +/- 7% of baseline versus 53%
      +/- 11%; P = NS). CONCLUSIONS: In vitro, sevoflurane and desflurane
      preconditioned human myocardium against hypoxia through a ROS-dependent
      mechanism.

PMID- 18042845
TI  - The safety and efficacy of extended thromboprophylaxis with fondaparinux after
      major orthopedic surgery of the lower limb with or without a neuraxial or deep
      peripheral nerve catheter: the EXPERT Study.
AB  - BACKGROUND: The benefit-risk ratio of extended fondaparinux therapy has not been
      assessed in patients undergoing major lower limb joint arthroplasty. Few data on
      the concomitant use of fondaparinux and continuous neuraxial or deep peripheral
      nerve blockade are available. We performed a prospective intervention study in
      patients undergoing major orthopedic surgery primarily designed to assess the
      efficacy of fondaparinux when drug administration was withheld for 48 h to permit
      removal of a neuraxial or deep peripheral nerve catheter. The safety and efficacy
      of extended fondaparinux therapy for the prevention of venous thromboembolism
      were also evaluated. METHODS: Patients received a daily subcutaneous injection of
      2.5 mg fondaparinux for 3 to 5 wk postoperatively. In patients with a neuraxial
      or deep peripheral nerve catheter, the catheter was removed 36 h after the last
      fondaparinux dose. The next fondaparinux dose was administered 12 h after
      catheter removal. The primary end points were symptomatic venous thromboembolism
      and major bleeding up to 4-6 wk after surgery. RESULTS: We recruited 5704
      patients. A neuraxial or deep peripheral nerve catheter was inserted in 1553
      (27%) patients and 78 (1.4%) patients, respectively. The rate of venous
      thromboembolism was 1.0% (54 of 5387). There was no difference between patients
      without (1.1%) or with (0.8%) a catheter (the upper limit of the 95% confidence
      interval of the odds ratio, 1.49, being below the predetermined noninferiority
      margin of 1.75). The incidence of major bleeding was 0.8% (42 of 5382). No
      neuraxial or perineural hematoma was reported. CONCLUSIONS: Once-daily
      subcutaneous injection of 2.5 mg fondaparinux given for 3 to 5 wk was effective
      and safe for prevention of venous thromboembolism after major orthopedic surgery.
      Temporary discontinuation of fondaparinux for 48 h permitted safe removal of a
      neuraxial or deep peripheral nerve catheter without decreasing thromboprophylatic
      efficacy.

PMID- 18042846
TI  - The role of heart rate variability in risk stratification for adverse
      postoperative cardiac events.
AB  - There is growing evidence of a strong association between the compromised
      autonomic nervous system and sudden cardiac death. Heart rate variability (HRV)
      measures are widely used to measure alterations in the autonomic nervous system.
      Several studies with cardiac patients show that decreased HRV as well as
      baroreceptor dysfunction are more powerful predictors for sudden cardiac death
      than established clinical predictors such as left ventricular ejection fraction.
      One-third of all postoperative complications and more than half of the deaths are
      due to cardiac complications. Several risk indices are useful for immediate
      perioperative short-term, but not for long-term outcome risk stratification of an
      individual patient. Currently, there are no clinically assimilated methods for
      long-term postoperative risk assessment. Recently, few studies have shown that
      preoperatively decreased HRV can independently predict postoperative long-term
      mortality. Further studies with surgical patients are needed to establish a
      possible predictive value of preoperative baroreceptor dysfunction, alone and
      combined with HRV, for short- and long-term postoperative outcome.

PMID- 18042847
TI  - Periorbital ecchymoses during general anesthesia in a patient with primary
      amyloidosis: a harbinger for bleeding?
AB  - Primary amyloidosis is a result of proliferation of a population of plasma cells
      that leads to an increased secretion of monoclonal immunoglobulins (amyloid).
      Amyloid protein infiltrates increase capillary fragility. Such capillaries can
      burst, even after minor stress, resulting in periorbital hemorrhage. We describe
      a 64-yr-old man with primary amyloidosis who underwent general anesthesia. His
      eyes were gently closed with tape. Upon removal of the tape bilateral periorbital
      purpura was noted. All coagulation studies were normal. The periorbital
      hemorrhage was attributed to amyloidosis-induced capillary fragility.

PMID- 18042848
TI  - A hypo-echoic, intramyocardial space: echocardiographic characteristics of an
      intramyocardial dissecting hematoma.

PMID- 18042849
TI  - Thrombotic occlusion of a bileaflet, mechanical mitral valve.

PMID- 18042850
TI  - Aneurysm of the atrioventricular membranous septum appearing as a right atrial
      cystic mass.

PMID- 18042851
TI  - Transesophageal echocardiographic detection of intracardiac BioGlue postmitral
      valve replacement.

PMID- 18042852
TI  - Malpositioned left ventricular assist device cannula: diagnosis and management
      with transesophageal echocardiography guidance.

PMID- 18042853
TI  - Ketamine does not increase pulmonary vascular resistance in children with
      pulmonary hypertension undergoing sevoflurane anesthesia and spontaneous
      ventilation.
AB  - BACKGROUND: The use of ketamine in children with increased pulmonary vascular
      resistance is controversial. In this prospective, open label study, we evaluated
      the hemodynamic responses to ketamine in children with pulmonary hypertension
      (mean pulmonary artery pressure >25 mm Hg). METHODS: Children aged 3 mo to 18 yr
      with pulmonary hypertension, who were scheduled for cardiac catheterization with
      general anesthesia, were studied. Patients were anesthetized with sevoflurane (1
      minimum alveolar anesthetic concentration [MAC]) in air while breathing
      spontaneously via a facemask. After baseline catheterization measurements,
      sevoflurane was reduced (0.5 MAC) and ketamine (2 mg/kg IV over 5 min) was
      administered, followed by a ketamine infusion (10 microg x kg(-1) x min(-1)).
      Catheterization measurements were repeated at 5, 10, and 15 min after completion
      of ketamine load. Data at various time points were compared (ANOVA, P < 0.05).
      RESULTS: Fifteen patients (age 147, 108 mo; median, interquartile range) were
      studied. Diagnoses included idiopathic pulmonary arterial hypertension (5),
      congenital heart disease (9), and diaphragmatic hernia (1). At baseline, median
      (interquartile range) baseline pulmonary vascular resistance index was 11.3 (8.2)
      Wood units; 33% of patients had suprasystemic mean pulmonary artery pressures.
      Heart rate (99, 94 bpm; P = 0.016) and Pao2 (95, 104 mm Hg; P = 007) changed
      after ketamine administration (baseline, 15 min after ketamine; P value). There
      were no significant differences in mean systemic arterial blood pressure, mean
      pulmonary artery pressure, systemic or pulmonary vascular resistance index,
      cardiac index, arterial pH, or Paco2. CONCLUSIONS: In the presence of
      sevoflurane, ketamine did not increase pulmonary vascular resistance in
      spontaneously breathing children with severe pulmonary hypertension.

PMID- 18042854
TI  - Programming pressure support ventilation in pediatric patients in ambulatory
      surgery with a laryngeal mask airway.
AB  - BACKGROUND: Anesthesia workstations with pressure support ventilation (PSV) are
      available, but there are few studies published on how to program flow-triggered
      PSV using a laryngeal mask airway (LMA) under general anesthesia in pediatric
      patients. METHODS: We studied 60 ASA I and II patients, from 2 mo to 14 yr,
      scheduled for ambulatory surgery under combined general and regional anesthesia
      with a LMA. Patients were classified according to their body weight as follows:
      Group A < or =10 kg, Group B 11-20 kg, and Group C >20 kg. All were ventilated in
      PSV using the following settings: positive end-expiratory pressure of 4 cm H2O,
      the minimum flow-trigger without provoking auto-triggering, and the minimum level
      of pressure support to obtain 10 mL/kg of tidal volume. RESULTS: The flow-trigger
      most frequently used in our study was 0.4 L/min, ranging from 0.2 to 0.6 L/min.
      We found no correlation between the flow-trigger setting and the patient's age,
      weight, compliance, resistance, or respiratory rate. There was a good correlation
      between the level of pressure support (Group A = 15 cm H2O, Group B = 10 cm H2O
      and Group C = 9 cm H2O) and age (P < 0.001), weight (P < 0.001), dynamic
      compliance (P < 0.001), and airway resistances (P < 0.001). CONCLUSIONS: PSV with
      a Proseal LMA in outpatient pediatric anesthesia can be programmed simply using
      the common clinical noninvasive variables studied. However, more studies are
      needed to estimate the level of pressure support that may be required in other
      clinical situations (respiratory pathology, endotracheal tubes, or other types of
      surgeries) or with other anesthesia workstations.

PMID- 18042855
TI  - A prospective evaluation of the POVOC score for the prediction of postoperative
      vomiting in children.
AB  - BACKGROUND: A score to predict postoperative vomiting (PV) in children (POVOC
      score) has recently been published but has not yet undergone an external
      validation. METHODS: We studied 673 patients (age 0-16 yr) undergoing a variety
      of surgical procedures (but excluding strabismus surgery, one of the risk factors
      according to the POVOC score) using standardized anesthesia techniques without
      administering antiemetics. The patients were prospectively screened for PV in the
      postoperative period and these incidences were compared with the predicted risk
      for PV according to the POVOC score. The POVOC score was evaluated with respect
      to its ease of use, discrimination, and calibration. RESULTS: Complete data to
      predict the risk for PV could be obtained in 95% of patients. The actual observed
      incidences of PV were 3.4, 11.6, 28.2, and 42.3% for the presence of 0, 1, 2, or
      3 risk factors, resulting in a regression line with a slope of 0.78 and an offset
      of 2.37. The area under the receiver operating characteristic curve was 0.72 (95%
      CI: 0.68-0.76). CONCLUSIONS: Using the POVOC score, PV in pediatric patients can
      be predicted with sufficient accuracy comparable to the results in adult
      patients, even if one of the risk factors is not applicable.

PMID- 18042856
TI  - An experimental and clinical evaluation of a novel central venous catheter with
      integrated oximetry for pediatric patients undergoing cardiac surgery.
AB  - BACKGROUND: Central venous oxygen saturation (ScvO2) accurately reflects
      cardiocirculatory function, but is not always feasible in pediatric patients.
      Using an experimental and clinical approach, we determined the accuracy of a
      novel pediatric central venous catheter with integrated fiberoptic oximetry,
      correlated ScvO2 to periprocedural vital variables, and tested its feasibility in
      pediatric cardiac surgery patients. METHODS: In five anesthetized pigs,
      hemodynamics (cardiac index [CI], heart rate; mean arterial blood [MAP]; mean
      pulmonary artery [MPAP], central venous pressure [CVP]), fiberoptic ScvO2 (ScvO2
      cath), and blood gas oximetry (ScvO2-blood) were measured during stable baseline
      conditions, preload reduction (caval occlusion), and dopamine infusion (5 mcg x
      kg(-1) x min(-1)). In 16 pediatric patients undergoing cardiac surgery (median
      age 8.4 mo; weight 8.0 kg), central venous oximetry catheters were placed
      percutaneously, and ScvO2-cath and hemodynamics recorded at several time-points
      during and until 24 h after surgery. Oximetry and hemodynamic data were compared
      by correlation (Pr) and the Bland-Altman analysis. RESULTS: There were no
      catheter-related complications. ScvO2-cath and ScvO2-blood measurements
      correlated significantly (P < 0.001) in both the experimental (Pr = 0.96) and
      clinical protocol (Pr = 0.94). A similar bias and precision over all time-points
      was detected in both protocols (Exp-bias: +0.03% +/- 4.11%; Clinical-bias: -0.03%
      +/- 4.41%). ScvO2-cath correlated (P < 0.001) with CI (Pr = 0.87), MAP (Pr =
      0.59), MPAP (Pr = 0.44), and CVP (Pr = 0.38) and estimated CI better than MAP (Pr
      = 0.61), MPAP (Pr = 0.38), CVP (Pr = 0.35), or heart rate (Pr = 0.25).
      CONCLUSION: Integrated central venous oximetry catheters provide accurate
      continuous ScvO2 monitoring in pediatric patients undergoing cardiac surgery.
      ScvO2 fiberoptic oximetry correlates better with changes in CI as compared to
      routine hemodynamic variables.

PMID- 18042857
TI  - The relationship between current intensity for nerve stimulation and success of
      peripheral nerve blocks performed in pediatric patients under general anesthesia.
AB  - BACKGROUND: We evaluated the relationship between the lowest current amperage
      used to obtain a motor response, the success rate and the incidence of
      neurological complications with peripheral nerve blocks (PNB) in pediatric
      patients under general anesthesia. METHODS: We reviewed the regional anesthesia
      database at The Children's Hospital of Philadelphia and included all pediatric
      patients who received a single-injection PNB under general anesthesia with the
      aid of a peripheral nerve stimulator between October 2002 and July 2006. Data
      analyzed included age, sex, type of block, stimulation threshold, presence of
      sensory and motor blockade, and neurological complications. RESULTS: Six-hundred
      sixty patients received a PNB during the study period. The average age of the
      patients was 13.8 yr (range = 2-18 yr). All the blocks were performed using a
      current ranging between 0.2 and 1 (median = 0.5 mA, interquartile range: 0.45
      0.55 mA). The overall success rate was 96%. There was no difference in success
      rate between blocks performed using a stimulation threshold of < or =0.5 or >0.5
      mA (96.3% vs 95.9%; P = 0.793). There was no correlation between the success rate
      and sex, type of block performed or intensity of current used. Two patients
      reported prolonged nerve blockade of the great toe and dorsum of the foot after a
      sciatic nerve block, which lasted for 72 h. No long-term sequelae were noted in
      our patients. CONCLUSION: In this study, a similar PNB success rate was observed
      with both a low (*0.5 mA) and a high stimulation threshold (>0.5 mA). Therefore,
      it may not be necessary to perform needle manipulations to achieve a low
      stimulation threshold (< or =0.5 mA), as this may increase the risk of
      intraneural injection.

PMID- 18042858
TI  - Reference values for kaolin-activated thromboelastography in healthy children.
AB  - BACKGROUND: The hemostatic system of children changes with age and differs
      significantly from the hemostatic system of adults. Age-specific reference values
      are therefore required for most hemostatic variables. Thromboelastography (TEG)
      is a point-of-care coagulation test that may provide superior evaluation and
      management of coagulopathies after cardiac surgery, when large-dose
      unfractionated heparin is administered for cardiopulmonary bypass. In this study,
      we established reference values for kaolin-activated TEG in healthy children, to
      facilitate accurate interpretation of pediatric TEG results. METHODS: Kaolin
      activated TEG was performed on 100 healthy children undergoing elective day
      surgery and 25 healthy adult volunteers. The following TEG variables were
      recorded: reaction time, coagulation time, alpha angle, maximum amplitude,
      percentage lysis 30 min after maximum amplitude was reached, and the coagulation
      index. Differences between age-groups were evaluated using analysis of variance.
      RESULTS: Age-specific reference values for kaolin-activated TEG in healthy
      children between 1 mo and 16 yr of age are presented. No significant differences
      between children and adults were observed. CONCLUSIONS: TEG results, from a
      particular clinical setting, must be compared to age-specific, as well as
      analyzer- and activator-specific, reference values to allow for correct
      interpretation of the results. Reference values provided here will be of use in
      acute clinical situations where a practical monitor of hemostasis is required.

PMID- 18042859
TI  - Society for Ambulatory Anesthesia guidelines for the management of postoperative
      nausea and vomiting.
AB  - The present guidelines were compiled by a multidisciplinary international panel
      of individuals with interest and expertise in postoperative nausea and vomiting
      (PONV) under the auspices of The Society of Ambulatory Anesthesia. The panel
      critically evaluated the current medical literature on PONV to provide an
      evidence-based reference tool for the management of adults and children who are
      undergoing surgery and are at increased risk for PONV. In brief, these guidelines
      identify risk factors for PONV in adults and children; recommend approaches for
      reducing baseline risks for PONV; identify the most effective antiemetic
      monotherapy and combination therapy regimens for PONV prophylaxis; recommend
      approaches for treatment of PONV when it occurs; and provide an algorithm for the
      management of individuals at increased risk for PONV.

PMID- 18042860
TI  - Estimation of optimal modeling weights for a Bayesian-based closed-loop system
      for propofol administration using the bispectral index as a controlled variable:
      a simulation study.
AB  - BACKGROUND: Implementing Bayesian methods in a model-based closed-loop system
      requires the integration of a standard response model with a patient-specific
      response model. This process makes use of specific modeling weights, called
      Bayesian variances, which determine how the specific model can deviate from the
      standard model. In this study we applied simulations to select the Bayesian
      variances yielding the optimal controller for a Bayesian-based closed-loop system
      for propofol administration using the Bispectral Index (BIS) as a controlled
      variable. METHODS: The relevant Bayesian variances determining the modeling
      process were identified. Each set of such Bayesian variances represents a
      potential controller. The set, which will result in optimal control, was
      estimated using calculations on a simulated population. We selected 625 candidate
      sets. Similar to our previous closed-loop performance study, we applied a
      simulation protocol to evaluate controller performance. Our population consisted
      of 416 virtual patients, generated using population characteristics from previous
      work. A BIS offset trajectory similar to a surgical case was used. RESULTS: We
      were able to develop, describe, and optimize the parameter setting for a patient
      individualized model-based closed-loop controller using Bayesian optimization.
      Selection of the optimal set yields a controller performing with the following
      median absolute prediction errors at BIS targets 30, 50, and 70: 12.9 +/- 2.87,
      7.59 +/- 0.74, and 5.76 +/- 1.03 respectively. CONCLUSIONS: We believe this
      system can be introduced safely into clinical testing for both induction and
      maintenance of anesthesia under direct observation of an anesthesiologist.

PMID- 18042861
TI  - The influence of hemorrhagic shock on the minimum alveolar anesthetic
      concentration of isoflurane in a swine model.
AB  - BACKGROUND: Although hemorrhagic shock decreases the minimum alveolar
      concentration (MAC) of inhaled anesthetics, it minimally alters the
      electroencephalographic (EEG) effect. Hemorrhagic shock also induces the release
      of endorphins, which are naturally occurring opioids. We tested whether the
      release of such opioids might explain the decrease in MAC. METHODS: Using the dew
      claw-clamp technique in 11 swine, we determined the isoflurane MAC before
      hemorrhage, after removal of 30% of the estimated blood volume (21 mL/kg of blood
      over 30 min), after fluid resuscitation using a volume of hydroxyethylstarch
      equivalent to the blood withdrawn, and after IV administration of 0.1 mg/kg of
      the mu-opioid antagonist naloxone. RESULTS: Hemorrhagic shock decreased the
      isoflurane MAC from 2.05% +/- 0.28% to 1.50% +/- 0.51% (P = 0.0007). Fluid
      resuscitation did not reverse MAC (1.59% +/- 0.53%), but additional
      administration of naloxone restored it to control levels (1.96% +/- 0.26%). The
      MAC values decreased depending on the severity of the shock, but the alterations
      in hemodynamic variables and metabolic changes accompanying fluid resuscitation
      or naloxone administration did not explain the changes in MAC. CONCLUSIONS:
      Consistent with previous reports, we found that hemorrhagic shock decreases MAC.
      In addition, we found that naloxone administration reversed the effect on MAC,
      and we propose that activation of the endogenous opioid system accounts for the
      decrease in MAC during hemorrhagic shock. Such an activation would not be
      expected to materially alter the EEG, an expectation consistent with our previous
      finding that hemorrhagic shock minimally alters the EEG.

PMID- 18042862
TI  - The anesthetic effects of etomidate: species-specific interaction with alpha 2
      adrenoceptors.
AB  - BACKGROUND: The IV anesthetic, etomidate, has structural and clinical
      similarities to specific alpha2-adrenoceptor agonists such as dexmedetomidine. We
      investigated whether the sedative effects of etomidate may be mediated by alpha2
      adrenoceptors. METHODS: The anesthetic potency of etomidate (1-20 microM) was
      determined in Xenopus laevis tadpoles in the absence and presence of the specific
      alpha2-adrenoceptor antagonist atipamezole (10 microM). Anesthesia was defined as
      loss of righting reflex. Nonlinear logistic regression curves were fitted to the
      data and half-maximal effective concentrations and the slopes of the curves were
      calculated. Additionally, sedative/ hypnotic effects of etomidate (8 mg/kg IP)
      were studied by rotarod test in wild-type (WT) mice and mice carrying targeted
      deletions of the alpha2A-adrenoceptor gene (alpha2A-KO). Data are presented as
      mean +/- sem. RESULTS: The fraction of anesthetized tadpoles increased with
      increasing concentrations of etomidate. Atipamezole significantly increased the
      half-maximal effective concentration of etomidate (4.5 +/- 0.2 microM; slope: 2.6
      +/- 0.3) to 8.4 +/- 0.4 microM (slope: 2.3 +/- 0.3). Etomidate resulted in time
      dependent sedative effects in all mice, as assessed by rotarod performance. In WT
      mice, the sedative effects of etomidate were not decreased by atipamezole (2
      mg/kg). Consistently, etomidate-induced sedation was not reduced in alpha2A-KO
      animals compared with WT mice. CONCLUSIONS: The sedative effects of etomidate
      exhibit a species-specific interaction with alpha2-adrenoceptors. Although the
      decrease in potency of etomidate by atipamezole may be caused by an interaction
      with alpha2-adrenoceptors in X. laevis tadpoles, results in mice indicate that
      the hypnotic effect of etomidate does not require alpha2-adrenoceptors.

PMID- 18042863
TI  - Secondary hyperalgesia in the postoperative pain model is dependent on spinal
      calcium/calmodulin-dependent protein kinase II alpha activation.
AB  - BACKGROUND: Spinally administered non-N-methyl-D-aspartate (NMDA), but not NMDA,
      receptor antagonists block primary (1 degree) and secondary (2 degrees)
      mechanical hyperalgesia and spontaneous pain after plantar incision. Hyperalgesia
      after thermal stimulation is also mediated by non-NMDA, but not NMDA, receptors.
      Although previous pain behavior studies in the thermal stimulus model
      demonstrated distinct protein kinase involvement downstream from spinal non-NMDA
      receptor activation, protein kinase signaling mechanisms have not been examined
      in the postoperative pain model. In the present study, we investigated whether
      spinal calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) mediates
      1 degree and/or 2 degrees hyperalgesia and spontaneous pain behavior after
      plantar incision. METHODS: Catheterized rats received a 1 cm incision in the
      hindpaw and were tested over 2 days for responses to mechanical stimulation
      adjacent to or 1 cm away from the incision site. Some rats received intrathecal
      (IT) pretreatment with a CaMKIIalpha inhibitor (14, 34, or 104 nmol KN-93) or
      vehicle (5% dimethyl sulfoxide in sterile saline). Separate groups received IT 34
      nmol or 104 nmol KN-93 and were tested for hindpaw weight bearing. Lumbar spinal
      cords were extracted 1 h after incision or sham treatment to measure
      phosphorylated CaMKIIalpha and alpha-amino-3-hydroxy-5-methylisoxazole-4
      proprionic acid GLUR1-831 in Western immunoblots. RESULTS: Incision increased
      spinal CaMKIIalpha and GLUR1-831 phosphorylation. Although pretreatment with all
      doses of IT KN-93 reduced the development of 2 degrees hyperalgesia, only 34 nmol
      KN-93 appeared to have an effect on 1 degrees hyperalgesia. IT KN-93 did not
      affect nonevoked pain. CONCLUSION: Spinal sensitization underlying incision
      evoked hyperalgesia involves spinal CaMKIIalpha activation and enhanced spinal
      alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor (AMPA)
      function.

PMID- 18042864
TI  - In vitro, lidocaine-induced axonal injury is prevented by peripheral inhibition
      of the p38 mitogen-activated protein kinase, but not by inhibiting caspase
      activity.
AB  - BACKGROUND: All local anesthetics (LAs) are, to some extent, neurotoxic. Toxicity
      studies have been performed in dissociated neuron cultures, immersing both axon
      and soma in LA. This approach, however, does not accurately reflect the in vivo
      situation for peripheral nerve blockade, where LA is applied to the axon alone.
      METHODS: We investigated lidocaine neurotoxicity in compartmental sensory neuron
      cultures, which are composed of one central compartment containing neuronal cell
      bodies and a peripheral compartment containing their axons, allowing for
      selective incubation. We applied lidocaine +/- neuroprotective drugs to neuronal
      somata or axons, and assessed neuron survival and axonal outgrowth. RESULTS:
      Lidocaine applied to the peripheral compartment led to a decreased number of
      axons (to 59% +/- 9%), without affecting survival of cell bodies. During axonal
      incubation with lidocaine, the p38 mitogen-activated protein kinase inhibitor
      SB203580 (10 microM) attenuated axonal injury when applied to the axon
      (insignificant reduction of maximal axonal distance to 93% +/- 9%), but not when
      applied to the cell body (deterioration of maximal axonal length to 48% +/- 6%).
      Axonal co-incubation of lidocaine with the caspase inhibitor z-vad-fmk (20
      microM) was not protective. CONCLUSIONS: Whereas inhibition of either p38 mitogen
      activated protein kinase or caspase activity promote neuronal survival after LA
      treatment of dissociated neuronal cultures, axonal degeneration induced by
      lidocain (40 mM) is prevented by p38 MAP kinase but not by caspase inhibition. We
      conclude that processes leading to LA-induced neurotoxicity in dissociated
      neuronal culture may be different from those observed after purely axonal
      application.

PMID- 18042865
TI  - Temporal and spatial determinants of sacral dorsal horn neuronal windup in
      relation to isoflurane-induced immobility.
AB  - BACKGROUND: Windup is a progressive increase in response of dorsal horn neurons
      to repetitive C-fiber stimulation that may underlie temporal summation of pain.
      We investigated the frequency- and intensity-dependency of windup, and the
      effects of isoflurane and N-methyl-d-aspartate (NMDA) receptor blockade, to
      determine if they parallel the influence of temporal and spatial summation of
      noxious stimuli on anesthetic requirements. METHODS: We recorded responses of rat
      sacral dorsal horn neurons to 20-s trains of electrical tail stimulation at
      different frequencies (0.3-10 Hz) and intensities (0.8-5 x stimulus threshold)
      during delivery of 0.7 to 1.3 minimum alveolar anesthetic concentration
      isoflurane. Summed responses (area under the curve [AUC] windup), initial
      response, absolute windup (AUC minus 20 times the initial response), and slope of
      windup were quantified. RESULTS: Increases in stimulus intensity and frequency
      progressively increased AUC windup (P < 0.01 for both) and correlated with
      isoflurane concentrations required for immobility (R2 = 0.98 and 0.97,
      respectively). Increasing the isoflurane concentration significantly suppressed
      each measure of windup elicited by low-intensity and low-frequency, but not high
      intensity and high-frequency stimulus trains. The initial response magnitude
      significantly correlated with slope of windup across stimulus intensities and
      isoflurane concentrations. The NMDA receptor antagonist MK801 significantly
      reduced windup (to 53%; P < 0.05) at 1 Hz. CONCLUSION: Windup of dorsal horn
      neurons at low stimulus intensities and frequencies increases isoflurane
      requirements for immobility via a NMDA receptor-dependent mechanism. At high
      stimulus intensities and frequencies, windup was resistant to isoflurane
      consistent with larger anesthetic requirements for immobility.

PMID- 18042866
TI  - Concentrations of isoflurane exceeding those used clinically slightly increase
      the affinity of methane, but not toluene, for water.
AB  - BACKGROUND: Inhaled anesthetics may affect proteins at the interface between
      membrane lipids and the surrounding aqueous phase. The underlying solution
      chemistry is not known. Because the hydrophobicity of nonpolar protein components
      importantly influences their conformation, we tested the hypothesis that
      isoflurane affects the solubility of two nonpolar compounds, methane and toluene,
      in saline. METHODS: Using a serial dilution technique, we determined the
      saline:gas partition coefficients (PCs) of methane and toluene at 37 degrees C in
      the absence of isoflurane and in the presence of approximately 1%, 5%, and 15%
      isoflurane. We also measured the effect on the vapor pressure of benzene produced
      by saturating benzene with either cyclopropane or chloroethane, anesthetics used
      in a previous study to demonstrate that their equilibration with benzene
      decreased the solubility of benzene in water. RESULTS: Clinically relevant
      concentrations of isoflurane (1% and 5%) did not affect the saline:gas PC of
      methane and toluene, but 15%-20% isoflurane increased the PC of methane (P <
      0.05) but not toluene. Saturating benzene with cyclopropane or chloroethane,
      decreased the vapor pressure of benzene in proportion to the amount of anesthetic
      dissolved in the benzene. CONCLUSION: Isoflurane has a weak antihydrophobic
      effect at concentrations far above the clinically relevant range, and this effect
      is unlikely to explain how anesthetics act. A previous study, which found that
      cyclopropane and chloroethane decreased the solubility of benzene in water,
      probably erred in its conclusion that these anesthetics interfered with the
      interaction of benzene and water. Instead, the anesthetics simply decreased the
      vapor pressure of benzene, doing so in accordance with Raoult's Law.

PMID- 18042867
TI  - New circulating-water devices warm more quickly than forced-air in volunteers.
AB  - BACKGROUND: Newer circulating-water systems supply more heat than forced-air,
      mainly because the heat capacity of water is much greater than for that of dry
      warm air and, in part, because they provide posterior as well as anterior
      heating. Several heating systems are available, but three major ones have yet to
      be compared directly. We therefore compared two circulating-water systems with a
      forced-air system during simulation of upper abdominal or chest surgery in
      volunteers. METHODS: Seven healthy volunteers participated on three separate
      study days. Each day, they were anesthetized and cooled to a core temperature
      near 34 degrees C, which was maintained for 45-60 min. They were then rewarmed
      with one of three warming systems until distal esophageal core temperature
      reached 36 degrees C or anesthesia had lasted 8 h. The warming systems were 1)
      energy transfer pads (two split torso pads and two universal pads; Kimberly
      Clark, Roswell, GA); 2) circulating-water garment (Allon MTRE 3365 for cardiac
      surgery, Akiva, Israel); and 3) lower body forced-air warming (Bair Hugger #525,
      #750 blower, Eden Prairie, MN). Data are presented as mean +/- sd; P < 0.05 was
      statistically significant. RESULTS: The rate of increase of core temperature from
      34 degrees C to 36 degrees C was 1.2 degrees C +/- 0.2 degrees C/h with the
      Kimberly Clark system, 0.9 degrees C +/- 0.2 degrees C/h with the Allon system,
      and 0.6 degrees C +/- 0.1 degrees C/h with the Bair Hugger (P = 0.002).
      CONCLUSIONS: The warming rate with the Kimberly Clark system was 25% faster than
      with the Allon system and twice as fast as with the Bair Hugger. Both circulating
      water systems thus warmed hypothermic volunteers in significantly less time than
      the forced-air system.

PMID- 18042868
TI  - The usefulness of an earphone-type infrared tympanic thermometer for
      intraoperative core temperature monitoring.
AB  - BACKGROUND: In this study we sought to determine the usefulness of a novel
      earphone-type infrared tympanic thermometer (IRT) for core temperature monitoring
      during surgery. METHODS: Two groups of patients were studied under different
      surgical conditions. The first group consisted of 18 adult patients (ASA I or II)
      who had been scheduled for elective surgery under general anesthesia. Before
      induction of general anesthesia, an earphone-type IRT was inserted into either
      the left or right ear canal. Tympanic temperature was monitored and recorded
      along with both rectal and esophageal temperatures during anesthesia. The second
      group consisted of eight adult patients (ASA II or III) who had been scheduled
      for cardiac surgery with cardiopulmonary bypass. Similar to the first group,
      tympanic temperature was measured by the earphone-type IRT and recorded along
      with the rectal and esophageal temperatures during cooling and rewarming phases
      of cardiopulmonary bypass. RESULTS: Study 1-The average temperature (+/-2 sd)
      measured with the IRT was +0.08 degrees C (+/-0.34 degrees C) above the
      esophageal temperature, and that with the rectal temperature was +0.11 degrees C
      (+/-0.55 degrees C) above the esophageal temperature. Study 2-The average
      temperature (+/-2 sd) measured with the IRT was +0.72 degrees C (+/-2.2 degrees
      C) above the esophageal temperature during cooling and warming phases during
      cardiac surgery with cardiopulmonary bypass. CONCLUSIONS: The earphone-type IRT
      might be used in a clinical setting for reliable and continuous core temperature
      monitoring during an operation.

PMID- 18042869
TI  - The 8-item Short-Form Health Survey and the physical comfort composite score of
      the quality of recovery 40-item scale provide the most responsive assessments of
      pain, physical function, and mental function during the first 4 days after
      ambulatory knee surgery with regional anesthesia.
AB  - BACKGROUND: We evaluated the validity and responsiveness of three instruments:
      the numeric rating scale (NRS) pain score, the 8-item Short-Form Health Survey
      (SF-8), and the 40-item Quality of Recovery from Anesthesia (QoR) Survey in 154
      outpatients undergoing anterior cruciate ligament reconstruction (ACLR). The
      objective was to provide a robust psychometric basis for outcome survey selection
      for surgical outpatients undergoing regional anesthesia without general
      anesthesia. METHODS: Patients undergoing ACLR with a standardized spinal
      anesthesia plan were randomized to receive a perineural catheter with either
      placebo injection-infusion, or injection-infusion with levobupivacaine. Patients
      completed the NRS, SF-8, and QoR instruments for four postoperative days to
      evaluate pain, physical function, and mental function. RESULTS: Regarding pain,
      neither the NRS nor the QoR offered advantages over the SF-8. Regarding physical
      function, the QoR physical independence composite offered no advantage over the
      SF-8 physical component summary. The QoR physical comfort composite assessed
      short-term changes in treatment-related side effects, and thus provided
      information not covered by the SF-8. Regarding mental function, the SF-8 mental
      component summary and QoR emotional state composite showed little change over the
      four days, although the latter measure showed higher responsiveness to change.
      CONCLUSIONS: For ACLR outpatients receiving regional anesthesia, the SF-8 is
      sufficient to assess postoperative pain and physical function. Adding the QoR
      physical comfort composite will help assess short-term side effects.

PMID- 18042870
TI  - Coordination of appointments for anesthesia care outside of operating rooms using
      an enterprise-wide scheduling system.
AB  - BACKGROUND: An anesthesia department implemented scheduling of anesthetics
      outside of operating rooms (non-OR) by clerks and nurses from other departments
      using its hospital's enterprise-wide scheduling system. METHODS: Observational
      studies chronicled the change over 2 yr as non-OR time was allocated by
      specialty, and nonanesthesia clerks and nurses scheduled anesthesia teams.
      Experimental studies investigated how tabular and graphical displays affected the
      scheduling of milestones (e.g., NPO times) and appointments before anesthetics.
      RESULTS: Anesthetics performed in allocated time increased progressively from 0%
      to 75%. Scheduling of anesthetics by nonanesthesia clerks and nurses increased
      progressively from 0% to 77%. Consistency of patient instructions was improved.
      The quality of resulting schedules was good. Implementation was not associated
      with worsening of multiple operational measures of performance such as
      cancellation rates, turnover times, or complaints. However, schedulers struggled
      to understand fasting and arrival times of patients, despite using a web site
      with statistically generated values in tabular formats. Experiments revealed that
      people ignored their knowledge that anesthetics can start earlier than scheduled.
      Participants made good decisions with both tabular and graphical displays when
      scheduling appointments preceding anesthesia. CONCLUSIONS: Enterprise-wide
      scheduling can coordinate anesthetics with other appointments on the same date
      and improve consistency and accuracy of patient instructions customized to the
      probability of an anesthetic starting early. The usefulness of implementation
      depends on the value in having more patient-centered care and/or in having
      patients arrive just in time for non-OR anesthesia, surgery, or regional block
      placement (e.g., at facilities with limited physical space).

PMID- 18042871
TI  - Changes in utilization of intraoperative laboratory testing associated with the
      introduction of point-of-care testing devices in an academic department.
AB  - BACKGROUND: Availability of point-of-care testing (POCT) technology may lead to
      unnecessary testing and expense without improving outcomes. We tested the
      hypothesis that frequency of intraoperative blood testing (IBT) would increase in
      association with installation of POCT devices in our surgical suites. METHODS: We
      performed a retrospective analysis of 38,115 electronic anesthesia records for
      cases performed in the 1 yr before and 1 yr after POCT installation. For each
      case, the frequency of IBT was tabulated and the change in frequency of IBT
      between the study periods was calculated for individual anesthesiologists, for
      the department as a whole, and for clusters of anesthetizing locations. RESULTS:
      For the department as a whole, there was no significant change between the before
      and after study periods in the 13% proportion of cases in which IBT was obtained.
      For cases in which IBT was used, there was no significant increase in the number
      of IBTs per case. CONCLUSIONS: We found no significant increase in the overall
      utilization of IBT associated with POCT presence in noncardiothoracic operating
      rooms.

PMID- 18042872
TI  - The effects of extracellular pH on vasopressin inhibition of ATP-sensitive K+
      channels in vascular smooth muscle cells.
AB  - BACKGROUND: Arginine vasopressin (AVP) inhibits ATP-sensitive potassium (K(ATP))
      channels and may help to restore vascular tone in patients with vasodilatory
      shock. In the present study, we investigated whether extracellular acidification
      modifies the inhibition of vascular K(ATP) channels by AVP. METHODS: We used a
      cell-attached patch-clamp configuration to investigate the effects of
      extracellular pH (pH(o)) on AVP-K(ATP) channel interaction in rat aortic smooth
      muscle cells. RESULTS: Bath application of AVP significantly inhibited
      extracellular acidification (pH(o) = 6.5)-induced K(ATP) channel activity in a
      concentration-dependent manner, with an half-maximal inhibitory concentration
      (IC50) value of 16.8 pM. Furthermore, bath application of AVP significantly
      inhibited pinacidil-induced K(ATP) channel activity at mild (pH(o) = 7.0) and
      severe (pH(o) = 6.5) extracellular acidification, with IC50 values of 266.7 and
      21.4 pM, respectively, but failed to significantly inhibit at normal pH (pH(o) =
      7.4) or under alkalosis (pH(o) = 9.0). Augmentation of AVP inhibition of vascular
      K(ATP) channels during extracellular acidification was eliminated by pretreatment
      with OPC-21268, a specific blocker of the V1 receptor, but not by a V2 blocker,
      OPC-31260. AVP-induced inhibition was also suppressed by pretreatment with a
      protein kinase C inhibitor, calphostin C. CONCLUSIONS: Our results suggest that
      AVP inhibits extracellular acidification-induced vascular K(ATP) channel
      activity, and that the inhibitory effects of AVP on vascular K(ATP) channels are
      enhanced by extracellular acidification via the V1 receptor-protein kinase C cell
      signaling pathway. The potent inhibition of vascular K(ATP) channels by AVP under
      acidic conditions may make it suitable for management of vasodilatory shock.

PMID- 18042873
TI  - Emergent retrograde tracheal intubation with a gum-elastic bougie in a trauma
      patient.
AB  - BACKGROUND: Patients with severe maxillofacial trauma pose a challenge when their
      airways must be secured. Often, emergent surgical airways are established when
      largyngoscopy or fiberoptic intubation are unsuccessful. When an airway cannot be
      surgically established, the anesthesiologist is forced to use novel approaches to
      airway management, but there are few descriptions of such techniques in the
      literature. METHODS: After unsuccessful laryngoscopy and a failed
      cricothyroidotomy and tracheostomy in a patient with deforming maxillofacial
      trauma, a gum-elastic bougie was inserted retrograde through a tracheal defect in
      a cephalad manner and exited the patient's mouth. RESULTS: The patient was
      successfully intubated using a modified retrograde technique through a tracheal
      defect with a gum-elastic bougie. CONCLUSIONS: When an uncontrolled airway cannot
      be secured surgically and a tracheal defect is present, retrograde intubation
      with a gum-elastic bougie may be considered as an emergent management option.

PMID- 18042874
TI  - The effects of centrally administered dexmedetomidine on cardiovascular and
      sympathetic function in conscious rats.
AB  - BACKGROUND: The alpha2-receptor is expressed in the brain, including the
      hypothalamus, where it is implicated in autonomic nervous system control. The
      effects of systemic administration of dexmedetomidine (DEX) on cardiovascular
      responses are well known; however, little is known about the effects of central
      administration of DEX on cardiovascular responses in conscious animals. In this
      study, we explored the effects and the mechanism of intracerebroventricularly
      (icv) administered DEX on cardiovascular responses and sympathetic nerve activity
      in conscious, unrestrained rats. METHODS: We administered DEX (0.5, 1, and 2
      microg/kg) icv and measured the mean arterial blood pressure (MAP), heart rate
      (HR), and plasma catecholamine in conscious rats (n = 58). Rats were also
      administered atropine (n = 8), propranolol (n = 8), or hexamethonium (n = 8) to
      assess the influence of vagal or sympathetic efferent activity in the DEX-induced
      responses. Some of the rats underwent carotid sinus and aortic nerve denervation
      to exclude the effect of the baroreceptor reflex. RESULTS:
      Intracerebroventricular administration of DEX dose-dependently decreased MAP, HR,
      and plasma norepinephrine. Large dose of DEX decreased plasma epinephrine. The
      amplitude of MAP reduction induced by DEX was reduced by hexamethonium or
      propranolol. The amplitude of HR reduction was reduced by atropine or
      propranolol. The amplitude of MAP and HR reduction induced by DEX were smaller in
      hexamethonium-pretreatment rats than in intact ones. The amplitude of MAP and HR
      reduction induced by DEX were larger in sinus and aortic nerve denervation rats
      than in intact ones. CONCLUSIONS: These results indicate that icv administration
      of DEX decreases MAP by sympathetic inhibition and decreases HR by sympathetic
      inhibition and vagal stimulation.

PMID- 18042875
TI  - Mechanisms of morphine enhancement of spontaneous seizure activity.
AB  - BACKGROUND: High-dose opioid therapy can precipitate seizures; however, the
      mechanism of such a dangerous adverse effect remains poorly understood. The aim
      of our study was to determine whether the neuroexcitatory activity of high-dose
      morphine is mediated by selective stimulation of opioid receptors. METHODS: Mice
      hippocampi were resected intact and bathed in low magnesium artificial
      cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1
      neurons. RESULTS: Application of morphine had a biphasic effect on the recorded
      spontaneous seizure-like events. In a low concentration (10 microM), morphine
      depressed electrographic seizure activity. Higher morphine concentrations (30 and
      100 microM) enhanced seizure activity in an apparent dose-dependent manner.
      Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of
      morphine. Selective mu and kappa opiate receptor agonists and antagonists
      enhanced and suppressed the spontaneous seizure activity, respectively. On the
      contrary, delta opioid receptor ligands did not have an effect. CONCLUSIONS: The
      proseizure effect of morphine is mediated through selective stimulation of mu and
      kappa opiate receptors but not the activation of the delta receptor system. The
      observed dose-dependent mechanism of morphine neuroexcitation underscores careful
      adjustment and individualized opioid dosing in the clinical setting.

PMID- 18042876
TI  - The accuracy of blood loss estimation after simulated vaginal delivery.
AB  - BACKGROUND: Visual blood loss estimation often underestimates blood loss. In this
      study we sought to determine the effect of calibrated drape markings on blood
      loss estimation in a simulated vaginal delivery. METHODS: Subjects were
      randomized to estimate simulated blood loss (300, 500, 1000, and 2000 mL) in
      calibrated or noncalibrated vaginal delivery drapes and then crossover. RESULTS:
      Visual blood loss estimation with noncalibrated drapes underestimated blood loss,
      with worsening accuracy at larger volumes (16% error at 300 mL to 41% at 2000
      mL). The calibrated drape error was <15% at all volumes. CONCLUSIONS: Calibrated
      vaginal delivery drapes improve blood loss estimation.

PMID- 18042877
TI  - A bibliometric analysis of global clinical research by anesthesia departments.
AB  - BACKGROUND: Few studies have investigated the diversity in research conducted by
      anesthesia-based researchers. We examined global clinical research attributed to
      anesthesia departments using Medline and Ovid databases. We also investigated the
      impact of economic development on national academic productivity. METHODS: We
      conducted a Medline search for English-language publications from 2000 to 2005.
      The search included only clinical research in which institutional affiliation
      included words relating to anesthesia (e.g., anesthesiology, anesthesia, etc.).
      Population and gross national income data were obtained from publicly available
      databases. Impact factors for journals were obtained from Journal Citation
      Reports (Thomson Scientific). RESULTS: There were 6736 publications from 64
      countries in 551 journals. About 85% of all publications were represented by 46
      journals. Randomized controlled trials constituted 4685 (70%) of publications.
      Turkey had the highest percentage of randomized controlled trials (88%). The
      United States led the field in quantity (20% of total) and mean impact factor
      (3.0) of publications. Finland had the highest productivity when adjusted for
      population (36 publications per million population). Publications from the United
      States declined from 23% in 2000 to 17% in 2005. CONCLUSIONS: Clinical research
      attributable to investigators in our specialty is diverse, and extends beyond the
      traditional field of anesthesia and intensive care. The United States produces
      the most clinical research, but per capita output is higher in European nations.

PMID- 18042878
TI  - Bilateral sciatic and femoral neuropathies, rhabdomyolysis, and acute renal
      failure caused by positioning during radical retropubic prostatectomy.
AB  - In the hyperlordotic position, the patient's hips are above the feet and head. We
      present a case of rhabdomyolysis, acute renal failure, and bilateral femoral and
      sciatic neuropathies caused by this position.

PMID- 18042879
TI  - Flat electroencephalogram caused by carbon dioxide pneumoperitoneum.
AB  - Hypercapnia during laparoscopy with CO2 is predicted in the following situations:
      compromised pulmonary function, retroperitoneal insufflation, and subcutaneous
      emphysema. We present a case of sudden electroencephalogram (EEG) depression in
      response to severe hypercapnia during laparoscopic ureteronephrectomy in a 77-yr
      old patient with chronic pulmonary emphysema. During intraperitoneal and
      retroperitoneal insufflation, subcutaneous emphysema and difficult ventilation
      occurred. Severe hypercapnia ensued, with pH = 6.94, and Paco2 = 137 mm Hg.
      Subsequent EEG activity was markedly depressed with a minimum Bispectral Index of
      4, accompanied by an increase in arterial blood pressure and heart rate.
      Termination of the laparoscopic procedure improved ventilation, EEG, and
      hemodynamics. These EEG changes may result from the narcotic properties of CO2 or
      hypercapnia-induced neurological abnormalities.

PMID- 18042880
TI  - The use of a laryngeal mask airway after a prolonged suspension laryngoscopy to
      preserve a vocal cord fat graft.
AB  - A 62-yr-old man presented for a microdirect laryngoscopy and vocal cord fat
      grafting under jet ventilation. After a prolonged laryngoscopy, the patient
      developed hypercapnea and upper airway obstruction secondary to traumatic
      epiglottitis. The placement of a laryngeal mask airway provided ventilation and
      allowed for direct visualization of the patient's inflamed epiglottis without
      disruption of the patient's fat graft. Because of its placement above the cords
      and its effectiveness in providing adequate ventilation, we propose intermittent
      laryngeal mask airway ventilation as a bridge, in lieu of endotracheal
      intubation, in microdirect laryngoscopy cases in which ventilation during
      emergence may be difficult and the insertion of an endotracheal tube would
      disrupt the surgical procedure.

PMID- 18042881
TI  - The ability of diagnostic spinal injections to predict surgical outcomes.
AB  - BACKGROUND: Since their first description more than 80 yr ago, the use of
      diagnostic spinal injections to predict surgical outcomes has been the subject of
      intense controversy. Because there are no standardized guidelines or substantive
      reviews on this topic, their use has remained inconsistent. METHODS: Diagnostic
      procedures included in this review were lumbar and cervical discography, lumbar
      facet blocks, lumbar and cervical selective nerve root blocks, and sacroiliac
      (SI) joint injections. We garnered materials via MEDLINE and OVID search engines,
      books and book chapters, bibliographic references, and conference proceedings.
      RESULTS: The lack of randomized, comparative studies for all blocks limited the
      conclusions that could be drawn. For the data that do exist, there is limited
      evidence that lumbar discography improves fusion outcomes, and no evidence that
      it influences disk replacement results. Although limited in scope, the current
      literature supports the notion that cervical discography improves surgical
      outcomes. There is strong evidence that lumbar selective nerve root blocks
      improve the identification of a symptomatic nerve root(s), and moderate evidence
      that both lumbar and cervical nerve root blocks improve surgical outcomes. The
      data supporting surgery for facet arthropathy are weak, and the use of screening
      blocks does not appear to improve outcomes. The data supporting SI joint fusion
      for degenerative, nontraumatic injuries are similarly weak. Because the most
      reliable method to diagnose a painful SI joint is with low volume, diagnostic
      injections, one might reasonably conclude that screening blocks improve surgical
      outcomes. However, this conclusion is not supported by indirect evidence.
      CONCLUSIONS: The ability to evaluate the effect of diagnostic blocks on surgical
      outcomes is limited by a lack of randomized studies, methodological flaws, and
      wide-ranging discrepancies with regard to injection variables, surgical
      technique, and outcome measures. More research is needed to optimize injection
      techniques and determine which, if any, diagnostic screening blocks can improve
      surgical outcomes.

PMID- 18042882
TI  - The analgesic effects of opioids and immersive virtual reality distraction:
      evidence from subjective and functional brain imaging assessments.
AB  - BACKGROUND: Immersive virtual reality (VR) is a novel form of distraction
      analgesia, yet its effects on pain-related brain activity when used adjunctively
      with opioid analgesics are unknown. We used subjective pain ratings and
      functional magnetic resonance imaging to measure pain and pain-related brain
      activity in subjects receiving opioid and/or VR distraction. METHODS: Healthy
      subjects (n = 9) received thermal pain stimulation and were exposed to four
      intervention conditions in a within-subjects design: (a) control (no analgesia),
      (b) opioid administration [hydromorphone (4 ng/mL target plasma level)], (c)
      immersive VR distraction, and (d) combined opioid + VR. Outcomes included
      subjective pain reports (0-10 labeled graphic rating scales) and blood oxygen
      level-dependent assessments of brain activity in five specific, pain-related
      regions of interest. RESULTS: Opioid alone significantly reduced subjective pain
      unpleasantness ratings (P < 0.05) and significantly reduced pain-related brain
      activity in the insula (P < 0.05) and thalamus (P < 0.05). VR alone significantly
      reduced both worst pain (P < 0.01) and pain unpleasantness (P < 0.01) and
      significantly reduced pain-related brain activity in the insula (P < 0.05),
      thalamus (P < 0.05), and SS2 (P < 0.05). Combined opioid + VR reduced pain
      reports more effectively than did opioid alone on all subjective pain measures (P
      < 0.01). Patterns of pain-related blood oxygen level-dependent activity were
      consistent with subjective analgesic reports. CONCLUSIONS: These subjective pain
      reports and objective functional magnetic resonance imaging results demonstrate
      converging evidence for the analgesic efficacy of opioid administration alone and
      VR distraction alone. Furthermore, patterns of pain-related brain activity
      support the significant subjective analgesic effects of VR distraction when used
      as an adjunct to opioid analgesia. These results provide preliminary data to
      support the clinical use of multimodal (e.g., combined pharmacologic and
      nonpharmacologic) analgesic techniques.

PMID- 18042883
TI  - The use of brain positron emission tomography to identify sites of postoperative
      pain processing with and without epidural analgesia.
AB  - It is not known how different analgesic regimes affect the brain when reducing
      postoperative pain. We performed positron emission tomography (PET) scans on a 69
      yr-old woman in the presence of moderate postoperative pain and then with
      epidural analgesia producing complete analgesia, during the first 2 days after
      total knee arthroplasty. Day 2 postsurgery PET scan data (no pain with epidural
      analgesia) were subtracted from Day 1 postsurgery PET scan data (time of moderate
      pain without epidural analgesia) to determine the brain regions activated.
      Postsurgical pain was associated with increased activity in the contralateral
      primary somatosensory cortex. Other brain regions showing increased postsurgical
      activity were the contralateral parietal cortex, bilateral pulvinar and
      ipsilateral medial dorsal nucleus of the thalamus, contralateral putamen,
      contralateral superior temporal gyrus, ipsilateral fusiform gyrus, ipsilateral
      posterior lobe, and contralateral anterior cerebellar lobe. This study
      demonstrates the feasibility of evaluating the central processing of acute
      postoperative pain using PET.

PMID- 18042884
TI  - The influence of race and socioeconomic factors on patient acceptance of
      perioperative epidural analgesia.
AB  - BACKGROUND: Ethnic minorities and patients of lower socioeconomic status may be
      more averse to the acceptance of epidural analgesia than nonminority counterparts
      and those of higher socioeconomic status, despite evidence for substantial
      benefit to the patient. METHODS: A scripted telephone survey was developed from
      the 2000 United States Census by a panel of experts. Contact was attempted at
      least twice for all patients listed for surgery at the Hospital of the University
      of Pennsylvania over a 4-mo period. RESULTS: Three thousand seven hundred thirty
      nine patients were called and 1265 subjects were successfully contacted and 1193
      consented, whereas 72 refused to participate. Seven hundred sixty-two subjects
      (64%) would accept an epidural if recommended by an anesthesiologist and 425
      (36%) would refuse. If the epidural was recommended by both the anesthesiologist
      and surgeon acceptance increased to 932 (78.5%). The univariate predictor of
      refusal of perioperative epidural analgesia was African American race. Univariate
      predictors of acceptance include full- or part-time employment, total household
      income >$50,001/yr, college graduate, prior epidural treatment, and knowledge of
      what an epidural is. When the potential confounders of race, total household
      income, employment, and education were included in a multivariate logistic
      regression model, African American race predicted refusal (odds ratio [OR], 0.58;
      P < 0.006; confidence interval [CI], 0.41-0.81) and was the only factor that
      predicted refusal or acceptance of epidural analgesia. CONCLUSIONS: Acceptance of
      perioperative epidural analgesia is strongly affected by race and socioeconomic
      status. Anesthesiologists need to recognize this potential barrier when trying to
      maximize patient comfort and outcome.

PMID- 18042885
TI  - Cardiovascular thromboembolic adverse effects associated with cyclooxygenase-2
      selective inhibitors and nonselective antiinflammatory drugs.
AB  - BACKGROUND: Concerns of increased cardiovascular (CV) thromboembolic adverse
      effects from nonsteroidal antiinflammatory drugs (NSAIDs, both nonselective [NS]
      NSAIDs and cyclooxygenase [COX]-2 selective inhibitors) have prevented their use
      despite numerous benefits. METHODS: In this descriptive review, we critically
      examine the randomized, active- and placebo-controlled studies, observational
      trials, and meta-analyses evaluating the CV adverse effects associated with long
      term and short-term use of COX-2 selective inhibitors and NS-NSAIDs. The
      potential mechanisms for these CV effects are also presented. RESULTS: Although
      the studies evaluating the CV risks have limitations, there appears to be an
      increased CV risk with both COX-2 selective inhibitors and NS-NSAIDs,
      particularly in high-risk patients. Therefore, the United States Food and Drug
      Administration has given a similar "boxed" warning highlighting the potential for
      increased risk of CV events associated with their use. Nevertheless, there are
      differences in the CV risks between COX-2 selective inhibitors (e.g., higher CV
      risk with rofecoxib than celecoxib) as well as differences in the CV risks
      between individual NS-NSAIDs (e.g., higher CV risks with diclofenac than
      naproxen). CONCLUSIONS: Until long-term, prospective, randomized, adequately
      powered, clinical studies in relevant patient populations have been completed,
      the CV risks associated with the use of NSAIDs, especially in high-risk patients,
      will likely continue to be controversial. Nevertheless, the benefits of their
      short-term (e.g., perioperative) use in patients without CV risks probably
      outweigh their potential CV adverse effects. Finally, careful risk/benefit
      assessment should be undertaken and both COX-2 selective inhibitors and NS-NSAIDs
      should be used with caution in patients with CV risk factors.

PMID- 18042886
TI  - Pregabalin: its pharmacology and use in pain management.
AB  - Pregabalin is a new synthetic molecule and a structural derivative of the
      inhibitory neurotransmitter gamma-aminobutyric acid. It is an alpha2-delta
      (alpha2-delta) ligand that has analgesic, anticonvulsant, anxiolytic, and sleep
      modulating activities. Pregabalin binds potently to the alpha2-delta subunit of
      calcium channels, resulting in a reduction in the release of several
      neurotransmitters, including glutamate, noradrenaline, serotonin, dopamine, and
      substance P. In this review, I will discuss the pharmacology of pregabalin and
      available efficacy studies in pain management. This review will focus on the
      advances in pregabalin pharmacology since my previous review in 2005.

PMID- 18042887
TI  - A differential diagnosis of hyperalgesia, toxicity, and withdrawal from
      intrathecal morphine infusion.
AB  - Opioid-induced hyperalgesia, toxicity, and withdrawal are phenomena that may
      occur with intrathecal opioid infusion. We present a case in which a patient
      received intrathecal morphine infusion, and then experienced a clinical course
      that may have involved hyperalgesia, toxicity, and/or withdrawal. The possible
      differential diagnosis of opioid-induced hyperalgesia, toxicity, and withdrawal,
      and its implications in clinical pain management, are discussed. This report
      demonstrates the complexity of treating patients with long-term continuous
      intrathecal opioids when modest adjustment of the intrathecal cocktail results in
      a paradoxical clinical course.

PMID- 18042888
TI  - Needlestick distal nerve injury in rats models symptoms of complex regional pain
      syndrome.
AB  - BACKGROUND: Complex Regional Pain Syndrome (CRPS)-I consists of chronic limb pain
      and dysautonomia triggered by traumas that sometime seem too trivial to be
      causative. Several pathological studies have identified minor distal nerve
      injuries (DNIs) in CRPS-I patients, but retrospective studies cannot establish
      causality. Therefore, we, prospectively investigated whether DNIs are sufficient
      to cause CRPS-like abnormalities in animals. We used needlestick, a cause of
      human CRPS, to evaluate lesion-size effects. METHODS: Left tibial nerves of male
      Sprague-Dawley rats were transfixed once by 30G, 22G, or 18G needles. Unoperated
      and sham-operated rats provided controls. Hindpaw sensory function, edema, and
      posture were measured. RESULTS: At Day-7 postoperatively, thresholds for
      ipsilateral-hindpaw withdrawal from Semmes-Weinstein monofilaments were reduced
      by > or =51% in 0% of sham-operated controls; 67% of rats that received 18G-DNI,
      88% that received 22G-DNI, and 89% that received 30G-DNI. Fifty-seven percent of
      all DNI rats had contralateral hindpaw "mirror" changes. The prevalence and
      severity of allodynia appeared independent of lesion size. Hyperalgesic responses
      to cold and pinprick applied to the plantar hindpaw were less common and were
      ipsilesional only, as was neurogenic hindpaw edema. Ipsilesional-only, tonic,
      dystonic-like hindpaw postures were evident in 42% of 18G-DNI, 6% of 22G-DNI, and
      no 30G-DNI or sham-operated control rats. The prevalence of postural
      abnormalities correlated with needle diameter (P = 0.001). Counting protein gene
      product 9.5-immunolabeled axons in skin biopsies from rats' ipsilesional hindpaws
      demonstrated mean reductions of 0% after 30G-needlestick, 15% after 22G
      needlestick, and 26% after 18G-needlestick, which closely reproduces the 29% mean
      epidermal neurite losses of CRPS-I patients. CONCLUSIONS: Needlestick DNI models
      several clinical and pathological features of human CRPS and provides direct
      prospective evidence that even minor DNI can cause CRPS-like abnormalities in
      rats.

PMID- 18042889
TI  - Inhibition of the cyclic adenosine monophosphate pathway attenuates neuropathic
      pain and reduces phosphorylation of cyclic adenosine monophosphate response
      element-binding in the spinal cord after partial sciatic nerve ligation in rats.
AB  - BACKGROUND: Recent reports have identified a role for cyclic adenosine
      monophosphate (cAMP) transduction in nociceptive processing. Spinal activation of
      the cAMP induced gene transcription through the activation of protein kinase A
      and cAMP response element-binding protein (CREB). Intrathecal injection of
      protein kinase A inhibitor reversed the mechanical hyperalgesia, whereas
      injection of CREB antisense attenuated tactile allodynia caused by partial
      sciatic nerve ligation (PSNL) in rats. In the present study, we aimed to assess
      the effects of spinal cAMP transduction on the nociceptive processing in a
      chronic neuropathic pain model. METHODS: PSNL was performed in male Sprague
      Dawley rats 1 wk after intrathecal catheterization. Nociception to mechanical and
      thermal stimuli was assessed at the hindpaw 2 h, 3, 7, and 14 days after PSNL.
      The effects of adenylate cyclase inhibitor, SQ22536 (0.7 mumol, intrathecal) on
      these nociceptions were evaluated. Changes in the expression and immunoreactivity
      of CREB and its phosphorylated proteins (CREB-IR and pCREB-IR) in the dorsal horn
      of the spinal cord were also measured. RESULTS: The expression of CREB-IR and
      pCREB-IR proteins was shown to increase for 2 wk after PSNL. The increase in
      pCREB was partially reversed by the blockade of the cAMP pathway in the early 3
      days, with a parallel increase in mechanical and thermal withdrawal thresholds.
      CONCLUSION: These results revealed the possible contribution of an increase in
      pCREB to the PSNL-induced tactile allodynia and thermal hyperalgesia. Modulation
      of the cAMP pathway may be clinically relevant if early intervention can be
      achieved in patients with chronic neuropathic pain.

PMID- 18042890
TI  - The influence of p38 mitogen-activated protein kinase inhibitor on synthesis of
      inflammatory cytokine tumor necrosis factor alpha in spinal cord of rats with
      chronic constriction injury.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) could trigger p38 mitogen
      activated protein kinase (MAPK) activation. Conversely phosphorylated p38 (p-p38)
      could induce the upregulation of TNF-alpha. In this study, we examined the
      hypothesis that chronic constrictive injury (CCI) of the sciatic nerve could
      promote spinal cord release of TNF-alpha and produce allodynia via the p38 MAPK
      pathway. METHODS: Sprague-Dawley rats were divided into five groups: 1) naive
      control rats, 2) sham surgery rats, 3) CCI surgery rats without treatment, 4) CCI
      surgery rats with saline (0.9%) treatment, and 5) CCI surgery rats with the p38
      MAPK inhibitor SB203580 treatment. In treatment groups, saline or SB203580 (2
      microg, twice a day) was given intrathecally starting 1 day before or 1 day or 7
      days after CCI. All rats were killed at different times after surgery to examine
      p38 MAPK activity and TNF-alpha levels in the spinal cord by Western blot
      analysis or immunohistochemistry. Mechanical allodynia was tested by a series of
      von Frey hairs 3, 7, and 14 days after surgery. RESULTS: p-p38 MAPK was
      significantly increased at 3, 7, and 14 days after CCI surgery compared with time
      matched shams (P < 0.05). Peripheral nerve injury induced mechanical allodynia
      and enhanced spinal concentrations of TNF-alpha (P < 0.05). Pretreatment or early
      treatment with SB203580 inhibited p38 MAPK activity, resulting in reduction of
      TNF-alpha synthesis and attenuation of mechanical allodynia (P < 0.05).
      CONCLUSION: p38 MAPK activation is one aspect of the signaling cascade that
      culminates in TNF-alpha synthesis and contributes to mechanical allodynia after
      peripheral nerve injury.

PMID- 18042891
TI  - The use of intraoperative ultrasound by anesthesiologists to facilitate the
      surgical management of peripheral nerve tumors of the upper extremity.
AB  - BACKGROUND: Traditional uses of ultrasound by anesthesiologists include
      transesophageal echocardiography, facilitation of vascular access, and guidance
      of peripheral nerve blocks. METHODS: In this case series, we report a novel
      application of ultrasound by anesthesiologists to facilitate the operative
      dissection of upper extremity peripheral nerve tumors. RESULTS: In four cases,
      ultrasound was used to intraoperatively locate the tumor, plan the safest
      surgical approach, and exclude tumor vascularity. CONCLUSIONS: Ultrasound can be
      used by anesthesiologists to facilitate the surgical management of peripheral
      nerve tumors.

PMID- 18042892
TI  - Thoracic paravertebral block for breast cancer surgery: a randomized double-blind
      study.
AB  - BACKGROUND: We examined in this randomized, double-blind study whether a
      multilevel paravertebral block performed before general anesthesia with propofol
      and a laryngeal mask enhances postoperative analgesia after breast cancer
      surgery. METHODS: Eighty-eight patients were randomized to receive paravertebral
      injections with either ropivacaine 0.5% (30 mL) or an equivalent amount of
      isotonic saline. Nine patients were excluded after randomization, thus 79
      patients remained for evaluation (ropivacaine, n = 38; placebo, n = 41).
      Variables of efficacy were the amount of fentanyl delivered by the patient
      controlled analgesia device in the postanesthesia care unit (PACU), postoperative
      pain measured on a numeric rating scale at regular intervals from the day of
      surgery and until the second postoperative day. RESULTS: The median consumption
      of fentanyl in the PACU was less in the ropivacaine group compared with the
      placebo group (0 microg [range: 0-250 microg] versus 100 microg [range: 0-800
      microg], P = 0.001). Also, fewer patients in the ropivacaine group reported pain
      > or =3 on the numbers rating scale in the PACU (13 vs 31, P < 0.0001). No
      statistical difference in pain scores or consumption of analgesics could be
      demonstrated after discharge from the PACU. CONCLUSIONS: A multilevel
      paravertebral block provides good analgesia for breast surgery, but the duration
      of analgesia is briefer than described in previous studies.

PMID- 18042893
TI  - A randomized controlled trial of femoral nerve blockade administered
      preclinically for pain relief in femoral trauma.
AB  - BACKGROUND: Analgesia at the location of the accident and on transport for
      femoral trauma is often delayed or insufficient. In this prospective, randomized,
      controlled study, we evaluated the preclinical use of femoral nerve blockade for
      reducing pain and anxiety compared with IV analgesia using metamizol. METHODS:
      Patients with painful femoral trauma, such as fracture or severe contusion, were
      randomized to receive at the site of the accident a femoral nerve blockade (n =
      31) or IV analgesia with metamizol (n = 31). A visual analog scale (VAS) was used
      to assess pain and anxiety. Variables were assessed at baseline, during transport
      and upon arrival at the hospital. RESULTS: In patients receiving the femoral
      nerve blockade, pain values decreased by half from VAS 86 +/- 6 mm at the site of
      the accident to VAS 41 +/- 15 mm during transport. Anxiety decreased by half from
      VAS 84 +/- 11 mm to VAS 39 +/- 14 mm. Heart rate decreased by 20 +/- 5 bpm. In
      the metamizol group, pain, anxiety, and heart rate did not decrease (P < 0.001).
      Time of treatment was 7.4 +/- 3.5 min longer in the femoral nerve blockade group.
      CONCLUSION: Preclinically administered femoral nerve blockade effectively
      decreases pain, anxiety, and heart rate after femoral trauma. Regional blockade
      is an option for out-of-hospital analgesia administered by a trained physician.

PMID- 18042894
TI  - The paramedian technique: a superior initial approach to continuous spinal
      anesthesia in the elderly.
AB  - BACKGROUND: Spinal anesthesia in elderly patients is frequently associated with
      significant technical difficulties. Thus, we compared the classical midline
      approach to the paramedian approach to perform continuous spinal anesthesia
      (CSA). METHODS: We prospectively studied 40 patients aged >75 yr who underwent
      open surgical repair of a hip fracture. These patients were randomly allocated to
      one of two groups: Group M: midline approach, and Group PM: paramedian approach.
      Patients were positioned in the lateral decubitus to receive CSA at L4-5 level.
      CSA was considered successful if cerebrospinal fluid was obtained through the
      needle. In case of initial failure in either approach, the same approach was
      repeated by the same operator. If two attempts were unsuccessful, the other
      anatomical approach was used by the same operator. If both approaches failed, a
      staff anesthesiologist performed a final attempt. In case of failure or
      insufficient block, the patient received general anesthesia. RESULTS: The success
      rate after the first attempt was 85% (17) for Group PM and 45% (9) for Group M (P
      = 0.02). All catheters were successfully introduced. No patient required general
      anesthesia. Vascular puncture after needle puncture was observed in six patients
      in Group M versus 0 in Group PM (P = 0.03), but none were of clinical
      consequence. No other clinically significant complications were observed.
      CONCLUSION: In summary, after the initial attempt, the paramedian approach is
      associated with an increased success rate, compared with the midline approach,
      during the performance of CSA in elderly patients.

PMID- 18042895
TI  - Piezoelectric vibrating needle and catheter for enhancing ultrasound-guided
      peripheral nerve blocks.
AB  - Ultrasound imaging has been used for performing single-injection peripheral nerve
      blocks and continuous catheters. One limitation with current technology is the
      inability to confirm the location of the needle or catheter tip. We describe a
      new needle and catheter design that permits distal tip visualization using color
      flow Doppler. An 18-gauge 100-mm insulated Tuohy needle and a 20-gauge 50-mm
      polyamide catheter (open tip) with a Teflon-coated steel stylet (B. Braun,
      Bethlehem, PA) were customized by adhering in place two piezoelectric actuators.
      These created 1-8 kHz vibrations when coupled to a function generator (FG502,
      Tektronix, Richardson, TX) and a 100 W audio amplifier (R3000, KLH, Sun Valley,
      CA). Mimicking a lateral popliteal fossa block, the needle and catheter were
      inserted into the leg of an unembalmed cadaver. When activated, the tip of each
      was highlighted in color when scanned in the short axis using the color Doppler
      mode of a two-dimensional ultrasound and a 12 MHz L38 probe (MicroMaxx, Sonosite,
      Bothell, WA). Vibration technology may be a useful adjunct while performing
      ultrasound-guided regional anesthesia. Further study evaluating its usefulness
      and safety in live tissue is warranted.

PMID- 18042896
TI  - The importance of transparency in industry-sponsored multicenter clinical
      studies.

PMID- 18042897
TI  - Spinal anesthesia research: let's not be hasty.

PMID- 18042898
TI  - When lack of addition really does add up.

PMID- 18042899
TI  - Extended release epidural morphine, far from ideal for postcesarean delivery pain
      control.

PMID- 18042900
TI  - The role of opioids in pain management.

PMID- 18042901
TI  - Consumer reports for anesthesia equipment: an idea whose time has come?

PMID- 18042902
TI  - Tracheomalacia due to short term ventilation after total hip arthroplasty in an
      adult with long standing goiter.

PMID- 18042903
TI  - Internet drug access runs rampant.

PMID- 18042904
TI  - Disruption of a laryngeal mask during removal.

PMID- 18042905
TI  - Perioperative complications during use of an obstructive sleep apnea protocol
      following surgery and anesthesia.

PMID- 18042906
TI  - The ever-useful infrared analyzer.

PMID- 18042907
TI  - The cover. Room in New York.

PMID- 18042908
TI  - A piece of my mind. It's simple, really.

PMID- 18042909
TI  - Scientists study "senescence" in cancer: therapies aim to hold cells in a
      nondividing state.

PMID- 18042910
TI  - Rapid diagnosis and treatment of TIAs help reduce recurrent stroke risk.

PMID- 18042911
TI  - Congress queries need for and safety of high-containment research laboratories.

PMID- 18042912
TI  - Diabetes and mortality risk after acute coronary syndromes.

PMID- 18042913
TI  - Diabetes and mortality risk after acute coronary syndromes.

PMID- 18042914
TI  - Risk of diabetes in patients with rheumatoid arthritis taking hydroxychloroquine.

PMID- 18042915
TI  - High-trauma fractures and low bone mineral density in older women and men.
AB  - CONTEXT: It is widely believed that fractures resulting from high trauma are not
      osteoporotic; however, this assumption has not been studied prospectively.
      OBJECTIVE: To examine the association between bone mineral density (BMD) and high
      trauma fracture and between high-trauma fracture and subsequent fracture in older
      women and men. DESIGN, SETTING, AND PARTICIPANTS: Two prospective US cohort
      studies in community-dwelling adults 65 years or older from geographically
      diverse sites. The Study of Osteoporotic Fractures followed up 8022 women for 9.1
      years (1988-2006). The Osteoporotic Fractures in Men Study followed up 5995 men
      for 5.1 years (2000-2007). MAIN OUTCOME MEASURES: Hip and spine BMD were assessed
      by dual-energy x-ray absorptiometry. Incident nonspine fractures were confirmed
      by radiographic report. Fractures were classified, without knowledge of BMD, as
      high trauma (due to motor vehicle crashes and falls from greater than standing
      height) or as low trauma (due to falls from standing height and less severe
      trauma). RESULTS: Overall, 264 women and 94 men sustained an initial high-trauma
      fracture and 3211 women and 346 men sustained an initial low-trauma fracture. For
      women, each 1-SD reduction in total hip BMD was similarly associated with an
      increased risk of high-trauma fracture (multivariate relative hazard [RH], 1.45;
      95% confidence interval [CI], 1.23-1.72) and low-trauma fracture (RH, 1.49; 95%
      CI, 1.42-1.57). Results were consistent in men (high-trauma fracture RH, 1.54;
      95% CI, 1.20-1.96; low-trauma fracture RH, 1.69; 95% CI, 1.49-1.91). Risk of
      subsequent fracture was 34% (95% CI, 7%-67%) greater among women with an initial
      high-trauma fracture and 31% (95% CI, 20%-43%) greater among women with an
      initial low-trauma fracture, compared with women having no high- or low-trauma
      fracture, respectively. Risk of subsequent fracture was not modeled for men.
      CONCLUSIONS: Similar to low-trauma nonspine fractures, high-trauma nonspine
      fractures are associated with low BMD and increased risk of subsequent fracture
      in older adults. High-trauma nonspine fractures should be included as outcomes in
      osteoporosis trials and observational studies.

PMID- 18042916
TI  - Factors associated with 5-year risk of hip fracture in postmenopausal women.
AB  - CONTEXT: The 329,000 hip fractures that annually occur in the United States are
      associated with high morbidity, mortality, and cost. Identification of those at
      high risk is a step toward prevention. OBJECTIVE: To develop an algorithm to
      predict the 5-year risk of hip fracture in postmenopausal women. DESIGN, SETTING,
      AND PARTICIPANTS: A total of 93,676 women who participated in the observational
      component of the Women's Health Initiative (WHI), a multiethnic longitudinal
      study, were used to develop a predictive algorithm based on commonly available
      clinical features. Selected factors that predicted hip fracture were then
      validated by 68,132 women who participated in the clinical trial. The model was
      tested in a subset of 10,750 women who had undergone dual-energy x-ray
      absorptiometry (DXA) scans for bone mass density assessment. MAIN OUTCOME
      MEASURE: The prediction of centrally adjudicated hip fracture, measured by the
      area under the receiver operator characteristic (ROC) curves. RESULTS: During a
      mean (SD) follow-up of 7.6 (1.7) years, 1132 hip fractures were identified among
      women participating in the observational study (annualized rate, 0.16%), whereas
      during a mean follow-up of 8.0 (1.7) years, 791 hip fractures occurred among
      women participating in the clinical trial (annualized rate, 0.14%). Eleven
      factors predicted hip fracture within 5 years: age, self-reported health, weight,
      height, race/ethnicity, self-reported physical activity, history of fracture
      after age 54 years, parental hip fracture, current smoking, current
      corticosteroid use, and treated diabetes. Receiver operating characteristic
      curves showed that the algorithm had an area under the curve of 80% (95%
      confidence interval [CI], 0.77%-0.82%) when tested in the cohort of different
      women who were in the clinical trial. A simplified point score was developed for
      the probability of hip fracture. Receiver operating characteristic curves
      comparing DXA-scan prediction based on a 10% subset of the cohort and the
      algorithm among those who participated the clinical trial were similar, with an
      area under the curve of 79% (95% CI, 73%-85%) vs 71% (95% CI, 66%-76%).
      CONCLUSION: This algorithm, based on 11 clinical factors, may be useful to
      predict the 5-year risk of hip fracture among postmenopausal women of various
      ethnic backgrounds. Further studies are needed to assess the clinical implication
      of the algorithm in general and specifically to identify treatment benefits.

PMID- 18042917
TI  - Glucose-insulin-potassium therapy in patients with ST-segment elevation
      myocardial infarction.
AB  - CONTEXT: The clinical benefit of glucose-insulin-potassium (GIK) infusion in
      patients with ST-segment elevation myocardial infarction (STEMI) is unclear.
      While some smaller trials suggest benefit, in the CREATE-ECLA trial, GIK infusion
      had no effect on 30-day mortality in 20,201 patients. OBJECTIVES: To determine
      the association between GIK infusion therapy and 30-day and 6-month outcomes in
      patients with STEMI. DESIGN, SETTING, AND PARTICIPANTS: Primary analysis of the
      OASIS-6 GIK randomized controlled trial of 2748 patients with acute STEMI;
      prespecified analyses of the combined trial data from the OASIS-6 GIK and CREATE
      ECLA GIK trial populations of 22,943 patients with acute STEMI; subgroup analysis
      on the timing of initiation of GIK infusion therapy and outcomes; and post hoc
      analyses exploring whether GIK infusion may cause early harm by increasing
      glucose and potassium levels and net fluid gain. INTERVENTION: High-dose GIK
      solution consisting of 25% glucose, 50 U/L of regular insulin, and 80 mEq/L of
      potassium infused at 1.5 mL/kg per hour for 24 hours. MAIN OUTCOME MEASURES:
      Mortality rates at 30 days and 6 months in the OASIS-6 GIK trial and rates of
      death, heart failure, and the composite of death or heart failure at 3 and 30
      days in the combined OASIS-6 GIK and CREATE-ECLA GIK trial populations. RESULTS:
      At 6 months, 148 (10.8%) GIK infusion patients and 143 (10.4%) control patients
      died in the OASIS-6 trial (hazard ratio [HR], 1.04; 95% CI, 0.83-1.31; P = .72);
      153 (11.1%) GIK patients and 185 (13.5%) control patients had heart failure (HR,
      0.83; 95% CI, 0.67-1.02; P = .08); and 240 (17.5%) GIK patients and 264 (19.2%)
      control patients had a composite of death or heart failure (HR, 0.91; 95% CI,
      0.76-1.08; P = .27). In the prespecified analyses of the combined trial data,
      there were 712 deaths (6.2%) in the GIK group and 632 deaths (5.5%) in the
      control group at 3 days (HR, 1.13; 95% CI, 1.02-1.26; P = .03). This difference
      disappeared by 30 days, with 1108 deaths (9.7%) in the GIK group and 1068 (9.3%)
      in the control group (HR, 1.04; 95% CI, 0.96-1.13; P = .33). GIK therapy
      increased levels of glucose, potassium, and net fluid gain postinfusion, all 3 of
      which predicted death after adjusting for multiple confounders. Adjusting for
      glucose, potassium, and net fluid gain eliminated the apparent increase in
      mortality at 3 days observed with GIK infusion, suggesting a direct association
      with these factors. Administration of GIK infusion within 4 hours of symptom
      onset yielded no benefit compared with later initiation. CONCLUSIONS: Infusion of
      GIK provided no benefit and may cause early harm following STEMI. Avoidance of
      infusion-related hyperglycemia, hyperkalemia, and net fluid gain may be advisable
      in future studies of metabolic modulation in patients with STEMI. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00064428.

PMID- 18042918
TI  - Dementia screening in primary care: is it time?

PMID- 18042919
TI  - The reemerging HIV/AIDS epidemic in men who have sex with men.

PMID- 18042920
TI  - Asymmetric paternalism to improve health behaviors.

PMID- 18042921
TI  - High-trauma fractures and bone mineral density.

PMID- 18042923
TI  - JAMA patient page. Hip fractures.

PMID- 18042924
TI  - Unreported VA data may affect SEER research, cancer surveillance, and statistics
      gathering.

PMID- 18042925
TI  - New NSCLC staging raises treatment issues.

PMID- 18042926
TI  - Trend toward noninferiority trials may mean more difficult interpretation of
      trial results.

PMID- 18042927
TI  - In Australia, patients and government at odds over mesothelioma treatment costs.

PMID- 18042928
TI  - StatBite: Mesothelioma incidence among U.S. men.

PMID- 18042929
TI  - 18Fluorodeoxyglucose positron emission tomography, a standard diagnostic tool in
      lung cancer.

PMID- 18042930
TI  - Targeting the tumor vasculature to improve the efficacy of oncolytic virus
      therapy.

PMID- 18042931
TI  - Lack of association of alcohol and tobacco with HPV16-associated head and neck
      cancer.
AB  - BACKGROUND: Human papillomavirus type 16 (HPV16) seropositivity and alcohol and
      tobacco use have been associated with risk of head and neck squamous cell
      carcinoma (HNSCC). However, it is less clear whether HPV16 influences HNSCC risk
      associated with alcohol and tobacco use. METHODS: Incident cases of HNSCC
      diagnosed between December 1999 and December 2003 were identified from nine
      medical facilities in Greater Boston, MA. Control subjects were frequency matched
      to case subjects on age, sex, and town of residence. A total of 485 case subjects
      and 549 control subjects reported information on lifetime smoking and alcohol
      consumption and provided sera, which was used to determine presence of HPV16
      antibodies. Unconditional logistic regression was used to estimate odds ratios
      (ORs) and 95% confidence intervals (CIs) of HNSCC risk by alcohol consumption
      (drinks per week: < 3, 3 to < 8, 8 to < 25, > or = 25) and smoking (pack-years:
      none, > 0 to < 20, 20 to < 45, > or = 45), adjusting for age, sex, race,
      education, and HPV16 serology. Polytomous logistic regression was used to
      estimate odds ratios and 95% confidence intervals for the association of HPV16
      serology, alcohol consumption, and tobacco use in site-specific analyses. All
      statistical tests were two-sided. RESULTS: The strongest risk factors by tumor
      site were smoking for laryngeal cancer, alcohol for cancer of the oral cavity,
      and HPV16 for pharyngeal cancer. For pharyngeal cancer, risk increased with
      increasing alcohol consumption (OR(> or = 25 versus < 3 drinks per week) = 5.1,
      95% CI = 2.4 to 11.0) and smoking (OR(> or = 45 pack-years versus never smoker) =
      6.9, 95% CI = 3.1 to 15.1) among HPV16-seronegative subjects but not among HPV16
      seropositive subjects (P(interaction, HPV16 serology and alcohol) = .002;
      P(interaction, HPV16 serology and smoking) = .007). Among light drinkers or never
      smokers, HPV16 seropositivity was associated with a 30-fold increased risk of
      pharyngeal cancer. CONCLUSIONS: Alcohol or tobacco use does not further increase
      risk of HPV16-associated pharyngeal cancer. HNSCC risk associated with smoking,
      alcohol, and HPV16 differs by tumor site.

PMID- 18042932
TI  - 18Fluorodeoxyglucose positron emission tomography in the diagnosis and staging of
      lung cancer: a systematic review.
AB  - Lung cancer is the leading cause of cancer-related death in industrialized
      countries. The overall mortality rate for lung cancer is high, and early
      diagnosis provides the best chance for survival. Diagnostic tests guide lung
      cancer management decisions, and clinicians increasingly use diagnostic imaging
      in an effort to improve the management of patients with lung cancer. This
      systematic review, an expansion of a health technology assessment conducted in
      2001 by the Institute for Clinical and Evaluative Sciences, evaluates the
      accuracy and utility of 18fluorodeoxyglucose positron emission tomography (PET)
      in the diagnosis and staging of lung cancer. Through a systematic search of the
      literature, we identified relevant health technology assessments, randomized
      trials, and meta-analyses published since the earlier review, including 12
      evidence summary reports and 15 prospective studies of the diagnostic accuracy of
      PET. PET appears to have high sensitivity and reasonable specificity for
      differentiating benign from malignant lesions as small as 1 cm. PET appears
      superior to computed tomography imaging for mediastinal staging in non-small cell
      lung cancer (NSCLC). Randomized trials evaluating the utility of PET in
      potentially resectable NSCLC report conflicting results in terms of the relative
      reduction in the number of noncurative thoracotomies. PET has not been studied as
      extensively in patients with small-cell lung cancer, but the available data show
      that it has good accuracy in staging extensive- versus limited-stage disease.
      Although the current evidence is conflicting, PET may improve results of early
      stage lung cancer by identifying patients who have evidence of metastatic disease
      that is beyond the scope of surgical resection and that is not evident by
      standard preoperative staging procedures. Further trials are necessary to
      establish the clinical utility of PET as part of the standard preoperative
      assessment of early-stage lung cancer.

PMID- 18042933
TI  - Association of diet-induced hyperinsulinemia with accelerated growth of prostate
      cancer (LNCaP) xenografts.
AB  - BACKGROUND: Prior research suggested that energy balance and fat intake influence
      prostate cancer progression, but the influence of dietary carbohydrate on
      prostate cancer progression has not been well characterized. We hypothesized that
      hyperinsulinemia resulting from high intake of refined carbohydrates would lead
      to more rapid growth of tumors in the murine LNCaP xenograft model of prostate
      cancer. METHODS: Athymic mice were injected subcutaneously with LNCaP human
      prostate cancer cells and, when tumors were palpable, were randomly assigned (n =
      20 per group) to high carbohydrate-high fat or low carbohydrate-high fat diets.
      Body weight and tumor volume were measured weekly. After 9 weeks, serum levels of
      insulin and insulin-like growth factor 1 (IGF-1) were measured by enzyme
      immunoassay. AKT activation and the levels of the insulin receptor in tumor cells
      were determined by immunoblotting. The in vitro growth response of LNCaP cells to
      serum from mice in the two treatment groups was measured based on tetrazolium
      compound reduction. All statistical tests were two-sided. RESULTS: After 9 weeks
      on the experimental diets, mice on the high carbohydrate-high fat diet were
      heavier (mean body weight of mice on the high carbohydrate-high fat diet = 34 g
      versus 29.1 g on the low carbohydrate-high fat diet, difference = 4.9 g, 95% CI =
      3.8 to 6.0 g; P = .003), experienced increased tumor growth (mean tumor volume in
      mice on high carbohydrate-high fat diet = 1695 versus 980 mm3 on low carbohydrate
      high fat diet, difference = 715 mm3, 95% CI = 608 to 822 mm3; P<.001), and
      experienced a statistically significant increase in serum insulin and IGF-1
      levels. Tumors from mice on the high carbohydrate-high fat diet had higher levels
      of activated AKT and modestly higher insulin receptor levels than tumors from
      mice on the low carbohydrate-high fat diet. Serum from mice on the high
      carbohydrate-high fat diet was more mitogenic for LNCaP cells in vitro than serum
      from mice fed the low carbohydrate-high fat diet. CONCLUSION: A diet high in
      refined carbohydrates is associated with increased tumor growth and with
      activation of signaling pathways distal to the insulin receptor in a murine model
      of prostate cancer.

PMID- 18042934
TI  - Effect of tumor microenvironment modulation on the efficacy of oncolytic virus
      therapy.
AB  - BACKGROUND: The tumor microenvironment is being increasingly recognized as an
      important determinant of tumor progression as well as of therapeutic response. We
      investigated oncolytic virus (OV) therapy-induced changes in tumor blood vessels
      and the impact of modulating tumor vasculature on the efficacy of oncolytic virus
      therapy. METHODS: Rat glioma cells (D74/HveC) were implanted intracranially in
      immune-competent rats. Seven days later, the rats (groups of 3-7 rats) were
      treated with oncolytic virus (hrR3), and, 3 days later, brains were harvested for
      evaluation. Some rats were treated with angiostatic cRGD peptide 4 days before
      oncolytic virus treatment. Some rats were treated with cyclophosphamide (CPA), an
      immunosuppressant, 2 days before oncolytic virus treatment. Changes in tumor
      vascular perfusion were evaluated by magnetic resonance imaging of live rats and
      by fluorescence microscopy of tumor sections from rats perfused with Texas red
      conjugated lectin immediately before euthanasia. Leukocyte infiltration in tumors
      was evaluated by anti-CD45 immunohistochemistry, and the presence of oncolytic
      virus in tumors was evaluated by viral titration. Changes in cytokine gene
      expression in tumors were measured by quantitative real-time polymerase chain
      reaction-based microarrays. Survival was analyzed by the Kaplan-Meier method. All
      statistical tests were two-sided. RESULTS: Oncolytic virus treatment of
      experimental rat gliomas increased tumor vascular permeability, host leukocyte
      infiltration into tumors, and intratumoral expression of inflammatory cytokine
      genes, including interferon gamma (IFN-gamma). The increase in vascular
      permeability was suppressed in rats pretreated with cyclophosphamide. Compared
      with rats treated with hrR3 alone, rats pretreated with a single dose of cRGD
      peptide before hrR3 treatment had reduced tumor vascular permeability, leukocyte
      infiltration, and IFN-gamma protein levels (mean IFN-gamma level for hrR3 versus
      hrR3 + cRGD = 203 versus 65.6 microg/mg, difference = 137 microg/mg, 95%
      confidence interval = 72.7 to 202.9 microg/mg, P = .006); increased viral titers
      in tumor tissue; and longer median survival (21 days versus 17 days, P<.001).
      CONCLUSIONS: A single dose of angiostatic cRGD peptide treatment before oncolytic
      virus treatment enhanced the antitumor efficacy of oncolytic virus.

PMID- 18042935
TI  - Re: Breast cancer incidence, 1980-2006: combined roles of menopausal hormone
      therapy, screening mammography, and estrogen receptor status.

PMID- 18042937
TI  - Re: Declines in invasive breast cancer and use of postmenopausal hormone therapy
      in a screening mammography population.

PMID- 18042936
TI  - Projecting individualized absolute invasive breast cancer risk in African
      American women.
AB  - BACKGROUND: The Breast Cancer Risk Assessment Tool of the National Cancer
      Institute (NCI) is widely used for counseling and determining eligibility for
      breast cancer prevention trials, although its validity for projecting risk in
      African American women is uncertain. We developed a model for projecting absolute
      risk of invasive breast cancer in African American women and compared its
      projections with those from the Breast Cancer Risk Assessment Tool. METHODS: Data
      from 1607 African American women with invasive breast cancer and 1647 African
      American control subjects in the Women's Contraceptive and Reproductive
      Experiences (CARE) Study were used to compute relative and attributable risks
      that were based on age at menarche, number of affected mother or sisters, and
      number of previous benign biopsy examinations. Absolute risks were obtained by
      combining this information with data on invasive breast cancer incidence in
      African American women from the NCI's Surveillance, Epidemiology and End Results
      Program and with national mortality data. Eligibility screening data from the
      Study of Tamoxifen and Raloxifene (STAR) trial were used to determine how the new
      model would affect eligibility, and independent data from the Women's Health
      Initiative (WHI) were used to assess how well numbers of invasive breast cancers
      predicted by the new model agreed with observed cancers. RESULTS: Tables and
      graphs for estimating relative risks and projecting absolute invasive breast
      cancer risk with confidence intervals were developed for African American women.
      Relative risks for family history and number of biopsies and attributable risks
      estimated from the CARE population were lower than those from the Breast Cancer
      Risk Assessment Tool, as was the discriminatory accuracy (i.e., concordance).
      Using eligibility screening data from the STAR trial, we estimated that 30.3% of
      African American women would have had 5-year invasive breast cancer risks of at
      least 1.66% by use of the CARE model, compared with only 14.5% by use of the
      Breast Cancer Risk Assessment Tool. The numbers of cancers predicted by the CARE
      model agreed well with observed numbers of cancers (i.e., it was well calibrated)
      in data from the WHI, except that it underestimated risk in African American
      women with breast biopsy examinations. CONCLUSIONS: The CARE model usually gave
      higher risk estimates for African American women than the Breast Cancer Risk
      Assessment Tool and is recommended for counseling African American women
      regarding their risk of breast cancer.

PMID- 18042938
TI  - Re: Declines in invasive breast cancer and use of postmenopausal hormone therapy
      in a screening mammography population.

PMID- 18042940
TI  - Regeneration in liver and pancreas: time to cut the umbilical cord?
AB  - Organisms that are capable of robust tissue regeneration, including the urodele
      amphibians, use mechanisms that recapitulate embryonic development to regrow
      organs. Although mammals are not so adept at regeneration, several adult tissues
      exhibit partial or complete regrowth after injury. An ability to influence growth
      in mammalian tissues has become more imperative with the emergence of
      "regenerative medicine" as a discipline. For this field to fulfill its promise of
      providing functional tissues for clinical use, a more detailed picture will be
      required of how adult human tissues maintain mass during normal homeostasis and
      after injury. Studies of developing and regenerating liver and pancreas now
      suggest that mammals use distinct programs to regulate tissue growth during
      embryogenesis and adulthood.

PMID- 18042939
TI  - Breast cancer risk among male BRCA1 and BRCA2 mutation carriers.
AB  - Men who carry germline mutations in the BRCA2 gene have a higher risk of
      developing breast carcinoma than men in the general population. Men who carry
      germline mutations in the BRCA1 gene may also be at a higher risk for breast
      carcinoma, but this association is not as well established. We evaluated the
      risks of developing breast carcinoma for male BRCA1 and BRCA2 mutation carriers
      in the US population based on data from 1939 families with 97 male subjects with
      breast carcinoma that were collected from eight centers across the National
      Cancer Institute's Cancer Genetics Network. At all ages, the cumulative risks of
      male breast cancer were higher in both BRCA1 and BRCA2 mutation carriers than in
      noncarriers. The relative risks of developing breast cancer were highest for men
      in their 30s and 40s and decreased with increasing age. Both the relative and
      cumulative risks were higher for BRCA2 mutation carriers than for BRCA1 mutation
      carriers. The estimated cumulative risk of breast carcinoma for male BRCA1
      mutation carriers at age 70 years was 1.2% (95% confidence interval [CI] = 0.22%
      to 2.8%) and for BRCA2 mutation carriers, 6.8% (95% CI = 3.2% to 12%).

PMID- 18042941
TI  - New insights into the mechanisms of SOS activation.
AB  - The activation of the small guanosine triphosphatase Ras is critical for many
      biological events. It is therefore not surprising that the ubiquitously expressed
      Ras guanine nucleotide exchange factor (GEF) SOS (Son of Sevenless), which
      couples protein tyrosine kinases to Ras activation, is under tight autoinhibitory
      control. Several studies have revealed how multiple regulatory domains might
      affect SOS activity. Most notably, a second Ras-binding site on SOS
      allosterically regulates the duration and amplitude of Ras activation. This
      allosteric Ras-GTP is produced by another GEF, Ras guanine nucleotide-releasing
      protein 1 (RasGRP1). SOS and RasGRP1 are both activated downstream of
      phospholipase D(2), and gain-of-function mutants of SOS contribute to inherited
      diseases. These studies not only enable us to better appreciate the complexity of
      the regulation of GEFs but also prompt us to reevaluate our current understanding
      of pathways that lead to Ras activation.

PMID- 18042942
TI  - Substrate-bound protein gradients for cell culture fabricated by microfluidic
      networks and microcontact printing.
AB  - Graded distributions of proteins are pivotal for many signaling processes during
      development, such as morphogenesis, cell migration, and axon guidance. Here, we
      describe a technique to fabricate substrate-bound stepwise protein gradients by
      means of a microfluidic network etched into a silicon wafer with an array of
      parallel 14-micrometer-wide channels, which can be filled with a series of
      arbitrarily chosen protein solutions. In a subsequent microcontact printing step,
      the protein pattern is transferred onto a surface and is used as a substrate for
      cell culture. Cellular responses to a defined microscopic pattern of a protein,
      such as guided axonal outgrowth and directed migration, cell polarization,
      changes in morphology, and signaling, can be thus studied in a controlled in
      vitro environment.

PMID- 18042943
TI  - Hunger in our own backyard: the face of hunger in the United States.

PMID- 18042944
TI  - Minding your Ps and Qs in specialized nutrition support.

PMID- 18042945
TI  - Considerations of study design.
AB  - Research projects attempt to answer specific questions. The particular study
      design that is selected will depend in large measure on the nature of the
      question and the time and resources available. There are 5 common categories of
      clinical questions; they relate to etiology, prognosis, utility of diagnostic
      tests, efficacy of proposed interventions, and cost of treatment in specific
      disease states. A number of study designs can be used. Case reports serve to
      memorialize unusual or novel aspects of diseases. Retrospective case series are
      useful for defining natural history. Case-control studies are used by
      epidemiologists to elucidate potential etiologies of diseases. Prospective cohort
      studies can be used to assess natural history or to assess potential disease
      etiologies. Controlled trials are designed to assess the efficacy of therapeutic
      interventions. Studies that define the sensitivity and specificity of diagnostic
      tests can be used to assess the utility of those tests. Economic analyses
      estimate the costs that particular diseases or therapies will require. Each of
      these study designs has limitations; with the exception of high-quality
      randomized trials, none of these study designs can establish a causative
      relationship between putative etiologic (or therapeutic) factors and disease
      (outcomes).

PMID- 18042946
TI  - Evidence-based medicine for nutrition support: an overview of the process.
AB  - On a daily basis, clinicians make decisions regarding therapies to result in the
      best outcome for their patients. These decisions should be based on the evidence
      in the literature, indicating a therapy will cause the best outcome. To
      facilitate this, many professional societies and scientific journals have
      published technical and scientific reviews, as well as evidence-based standards
      of care focused on many issues of nutrition support practice. This paper provides
      an overview of how these reviews and standards of care are derived to promote
      both the understanding of what they can and cannot do to enhance clinical
      practice.

PMID- 18042947
TI  - Outcomes research in specialized nutrition support.
AB  - Outcomes research can play an important role in the development and evolution of
      the specialty practice of nutrition support. This manuscript discusses the
      current state and future prospect of outcomes research in specialized nutrition
      support. It is concluded that there is an important role in the field for
      research that focuses on "what works, and what does not" in nutrition support
      practice.

PMID- 18042948
TI  - Funding nutrition research: where's the money?
AB  - While a great idea that can be developed into a viable hypothesis is central to
      the development of a meritorious research proposal, without funding, the evidence
      base supporting or reputing a hypothesis cannot be advanced. A wide variety of
      funding sources exist for nutrition research, including governmental,
      organizational, industrial, and intramural-based funding; however, understanding
      the "language" of research funding can be challenging. This review provides an
      overview of funding sources, guidelines for securing funding, and recommendations
      to support a successful application for clinical nutrition research.

PMID- 18042949
TI  - Understanding institutional review boards: practical guidance to the IRB review
      process.
AB  - The purpose of this paper is to provide practical guidance to assist
      investigators in the preparation of materials and obtaining approval for research
      projects that require oversight by an institutional review board (IRB). The
      central requirements for IRB approval and core considerations of IRBs are
      described. Specific suggestions for investigators regarding how to prepare their
      IRB applications to anticipate and address potential IRB concerns and questions
      are proposed. When researchers are familiar with these criteria and how they may
      be interpreted by an IRB, they can avoid deferrals or lengthy requests for
      protocol modifications or clarifications. General tips regarding the preparation
      of IRB submission materials that may allow for a smoother IRB review process are
      also discussed. A brief list of additional resources for investigators is
      appended.

PMID- 18042950
TI  - Biostatistics primer: part I.
AB  - Biostatistics is the application of statistics to biologic data. The field of
      statistics can be broken down into 2 fundamental parts: descriptive and
      inferential. Descriptive statistics are commonly used to categorize, display, and
      summarize data. Inferential statistics can be used to make predictions based on a
      sample obtained from a population or some large body of information. It is these
      inferences that are used to test specific research hypotheses. This 2-part review
      will outline important features of descriptive and inferential statistics as they
      apply to commonly conducted research studies in the biomedical literature. Part 1
      in this issue will discuss fundamental topics of statistics and data analysis.
      Additionally, some of the most commonly used statistical tests found in the
      biomedical literature will be reviewed in Part 2 in the February 2008 issue.

PMID- 18042951
TI  - Writing a scientific paper.
AB  - Scientific papers are written to a rigid format, composed of 4 sections, which
      correspond with the stages of the scientific method. This essay describes the
      relationship of the standard sections of a paper to the stages of the scientific
      method. Also for discussion will be the timing of the preparation of the paper
      and the relationship between the experimental protocol and the eventual paper.

PMID- 18042952
TI  - A "how-to" guide in preparing abstracts and poster presentations.
AB  - The preparation of an abstract or poster to share information from a project or
      case report with colleagues is a professional goal for many nutrition support
      practitioners. This paper provides an approach to help practitioners prepare an
      abstract for submission and subsequently a poster for presentation at a meeting.
      A nutrition support question that required collecting and evaluating information,
      or a unique patient case or case series, can serve as the focus of an abstract
      and subsequent poster. The professional meeting selected should be appropriate
      for the abstract topic, and the authors should closely adhere to the
      organization's abstract submission guidelines. The well-prepared abstract will
      then serve as the outline for the poster content; the visual aspect of the poster
      is also important to effectively communicate the information to colleagues at the
      meeting. Adequate time is required to prepare both the abstract and the poster in
      order to fittingly reflect the value of the information. Efforts in preparing the
      abstract will be worthwhile once the abstract has been accepted by reviewers for
      a poster session at the meeting. Likewise, the effort in preparing the poster in
      advance allows the presenter to enjoy the poster session and discuss the project
      with colleagues.

PMID- 18042953
TI  - The bits and bytes to advanced graduate degree programs.
AB  - Lifelong learning may afford the dietetics professional more opportunities for
      career advancement, a richer self-satisfaction, and a revived confidence
      regarding career choices. The avenue to lifelong learning is a process unique to
      every health professional because of individual differences in interest and work
      arenas. Learning activities may take the form of continuing education conferences
      or certificate programs, advanced or specialty training, or academic degree
      programs. These programs may be in one's local community or may be accessed via
      distance learning. This paper will focus on advanced-degree academic programs
      using the distance education route. Characteristics of technologically savvy
      programs and learners will be addressed.

PMID- 18042954
TI  - Pediatric intestinal failure: nutrition, pharmacologic, and surgical approaches.
AB  - Intestinal failure (IF) is a condition where there is insufficient functional
      bowel to allow for adequate nutrient and fluid absorption to sustain adequate
      growth in children. Several etiologies can predispose to IF, including
      necrotizing enterocolitis, gastroschisis, and intestinal atresias. Intestinal
      rehabilitation can be seen as a 3-pronged strategy merging nutrition,
      pharmacologic, and surgical approaches to achieve the ultimate goal of enteral
      nutrition. Nutrition approaches should seek to facilitate transition from
      parenteral nutrition (PN) to enteral nutrition because prolonged use of PN is
      associated with severe morbidity and mortality. Enteral nutrition, on the other
      hand, promotes and enhances an adaptive response in the intestine. Medications
      used in the treatment of IF may help alleviate symptoms of diarrhea, bacterial
      overgrowth, and gastrointestinal dysmotility. Surgical procedures, such as
      longitudinal intestinal lengthening and tapering (LILT) or serial transverse
      enteroplasty (STEP), can increase mucosal surface area and may enhance intestinal
      adaptation. IF is a difficult disease process with a complex patient population
      and is best guided through this 3-pronged approach by a multidisciplinary team
      featuring surgeons, gastroenterologists, dietitians, pharmacists, and nurses.

PMID- 18042955
TI  - The role of an intravenous fat emulsion composed of fish oil in a parenteral
      nutrition-dependent patient with hypertriglyceridemia.
AB  - Hypertriglyceridemia is a common complication in patients receiving parenteral
      nutrition (PN). Management typically involves withholding the IV fat emulsion
      (IVFE) until serum triglyceride levels normalize. In some instances, this
      practice may predispose patients to the development of essential fatty acid
      deficiency (EFAD) unless alternative therapies such as oral or topical oils are
      used. This is especially true in patients unable to tolerate enteral intake. We
      describe the management of hypertriglyceridemia in a 12-year-old boy dependent on
      PN who developed EFAD due to prolonged use of fat-free PN. His course was further
      complicated by PN-associated liver disease. Treatment involved the use of an IVFE
      derived from fish oils. Within 3 weeks, there was clinical improvement in EFAD
      and hypertriglyceridemia. The patient's triene:tetraene ratio decreased from
      0.207 to 0.044 (normal: 0.013-0.05). Similarly, his serum triglyceride levels
      decreased from 628 mg/dL to 183 mg/dL (normal: <200 mg/dL). After 2 months of
      treatment, he was successfully transitioned to enteral feedings; hepatic function
      normalized, as did the essential fatty acid profile and serum triglycerides
      levels. This suggests that using fish-oil-based IVFE may be an effective
      alternative to conventional IVFE in PN-dependent patients whose clinical course
      is complicated by hypertriglyceridemia.

PMID- 18042956
TI  - Complications after bariatric surgery: survey evaluating impact on the practice
      of specialized nutrition support.
AB  - BACKGROUND: The rapid growth of obesity rates has affected the practice of
      specialized nutrition support in various ways. One area that deserves special
      consideration is the impact that bariatric surgery, in particular complications
      resulting from bariatric surgery, has made on nutrition support practice. A
      descriptive survey was designed to evaluate this impact and to assess the various
      approaches to nutrition assessment and interventions in the postoperative
      bariatric surgery patient. METHODS: A web-based survey consisting of 17 questions
      was administered in April 2006 to American Society for Parenteral and Enteral
      Nutrition (A.S.P.E.N.) members with available e-mail addresses. Participants were
      queried about professional background, primary practice setting, and various
      issues related to their involvement in the care of bariatric surgery patients.
      RESULTS: There were 467 responses returned out of 3400 surveys delivered (14%
      response rate). Sixty percent of responders estimated they were consulted to see
      1-10 patients requiring specialized nutrition support over the previous year as a
      result of complications of bariatric surgery. The most common indications for
      specialized nutrition support in these patients were anastomotic leak/fistula
      (49%) and chronic nausea/vomiting (27%). When estimating calorie goals, 62% used
      an adjusted body weight, 15% used ideal body weight, and 14% used actual weight.
      When estimating protein goals, 56% used an adjusted body weight, 29% used ideal
      body weight, and 8% used actual weight. CONCLUSION: These observations provide
      impetus for guideline development and highlight the priority for further research
      regarding the best practices to ensure that postoperative bariatric surgery
      patients receive safe and appropriate nutrition support.

PMID- 18042957
TI  - Nonvitamin, nonmineral dietary supplementation in HIV-positive people.
AB  - BACKGROUND: Many consumers with chronic diseases attempt to take control of their
      health by using dietary supplements. The objective of this study was to describe
      current nonvitamin, nonmineral (NVNM) supplement use of HIV-infected persons in
      the Nutrition for Healthy Living (NFHL) cohort, the financial burden that buying
      these supplements might pose to this population, and to review current literature
      on potential interactions between NVNM supplements. METHODS: At baseline visit,
      participants were educated by a registered dietitian on keeping a complete 3-day
      food record (including all supplements) for 2 weekdays and 1 weekend day. Seventy
      two subjects reported consumption of NVNM supplements, and their food records
      were reviewed in detail. RESULTS: Each of the 72 subjects in this study used a
      mean of 6 NVNM supplements, which may have been in the form of a pill, powder,
      bar, or liquid. The 6 most common were glutamine (51%), N-acetyl-cysteine (36%),
      fish oil (33%), alpha-lipoic acid (32%), acetyl-l-carnitine (28%), and coenzyme
      Q10 (28%). Participants were also taking an average of 4 vitamin/mineral
      supplements; the 6 most common were multivitamin/multimineral (83%), vitamin E
      (51%), vitamin C (47%), vitamin B complex (43%), calcium (29%), and selenium
      (28%). CONCLUSIONS: With a total of 107 different types of NVNM supplements, our
      estimated cost examples indicated a weekly supplement regimen cost of between $25
      and $40 dollars. According to literature review, taking an NVNM supplement may
      involve some risk because many components have not been studied and these
      products are not tightly regulated.

PMID- 18042958
TI  - Nutrition support for head and neck cancer patients.

PMID- 18042960
TI  - Using physical barriers to reduce the spread of respiratory viruses.

PMID- 18042961
TI  - Physical interventions to interrupt or reduce the spread of respiratory viruses:
      systematic review.
AB  - OBJECTIVE: To systematically review evidence for the effectiveness of physical
      interventions to interrupt or reduce the spread of respiratory viruses. DATA
      EXTRACTION: Search strategy of the Cochrane Library, Medline, OldMedline, Embase,
      and CINAHL, without language restriction, for any intervention to prevent
      transmission of respiratory viruses (isolation, quarantine, social distancing,
      barriers, personal protection, and hygiene). Study designs were randomised
      trials, cohort studies, case-control studies, and controlled before and after
      studies. DATA SYNTHESIS: Of 2300 titles scanned 138 full papers were retrieved,
      including 49 papers of 51 studies. Study quality was poor for the three
      randomised controlled trials and most of the cluster randomised controlled
      trials; the observational studies were of mixed quality. Heterogeneity precluded
      meta-analysis of most data except that from six case-control studies. The highest
      quality cluster randomised trials suggest that the spread of respiratory viruses
      into the community can be prevented by intervening with hygienic measures aimed
      at younger children. Meta-analysis of six case-control studies suggests that
      physical measures are highly effective in preventing the spread of SARS:
      handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval
      0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52);
      wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03); wearing N95 masks (0.09,
      0.03 to 0.30; NNT=3, 2.37 to 4.06); wearing gloves (0.43, 0.29 to 0.65; NNT=5,
      4.15 to 15.41); wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12); and
      handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66
      to 4.97). The incremental effect of adding virucidals or antiseptics to normal
      handwashing to decrease the spread of respiratory disease remains uncertain. The
      lack of proper evaluation of global measures such as screening at entry ports and
      social distancing prevent firm conclusions being drawn. CONCLUSION: Routine long
      term implementation of some physical measures to interrupt or reduce the spread
      of respiratory viruses might be difficult but many simple and low cost
      interventions could be useful in reducing the spread.

PMID- 18042962
TI  - Dying in a nursing home: the role of local bed supply in nursing home discharges.
AB  - OBJECTIVE: The relationship of nursing home (NH) discharges due to death to NH
      bed supply and hospital bed supply was examined. METHOD: Data on discharges came
      from the 1999 National Nursing Home Survey (N = 6,335). County-level bed supply,
      controls for hospice agency supply, and a nursing facility's percentage of area
      NH beds came from the Area Resource File. Multinomial logistic regression was
      used to compare deaths with live discharges. Marginal effects were calculated.
      RESULTS: Discharges due to death increased with increasing NH bed supply and
      decreased in areas with greater hospital bed supply, areas where hospitalizations
      were more likely. Hospice supply and a facility's share of area NH beds also
      affected the probability of discharges due to death. DISCUSSION: Supply factors
      appear related to discharge decisions in a manner affecting the probability of
      discharges due to death, although the magnitude of the relationship may be less
      than expected.

PMID- 18042963
TI  - Effect of chair design on feed-forward postural control in sitting.
AB  - The objective of this study was to determine if a forward-tilted seat and the
      resultant semi-kneeling body position associated with sitting on the Balans Multi
      Chair (BMC) affect postural control in sitting. Nine healthy subjects were seated
      on either the BMC or a regular (REG) chair with their arms extended. They were
      instructed to induce self-initiated body perturbations in four different
      directions by exerting brief pulses of force against a stationary frame
      positioned in front of them. Electromyographic (EMG) activities of trunk and leg
      muscles were recorded before and during the perturbations. The results show that
      sitting on both types of chairs was associated with anticipatory activation of
      trunk and upper leg muscles. In contrast, anticipatory activation of distal
      muscles was observed while sitting only on the REG chair and was absent while
      sitting on the BMC. The outcome of the study suggests that although the forward
      tilting seat and semi-kneeling body position might help in preserving a normal
      lordosis, it is not associated with anticipatory activation of lower leg muscles,
      which might reduce the ability of an individual to counteract self-initiated body
      perturbations. These findings stress the important role of chair designs in the
      control of sitting posture.

PMID- 18042964
TI  - Bipedal locomotion of bonnet macaques after spinal cord injury.
AB  - Experimental studies concerning the analysis of locomotor behavior in spinal cord
      injury research are widely performed in rodent models. The purpose of this study
      was to quantitatively evaluate the degree of functional recovery in reflex
      components and bipedal locomotor behavior of bonnet macaques (Macaca radiata)
      after spinal contusive injury. Six monkeys were tested for various reflex
      components (grasping, righting, hopping, extension withdrawal) and were trained
      preoperatively to walk in bipedal fashion on the simple and complex locomotor
      runways (narrow beam, grid, inclined plane, treadmill) of this investigation. The
      overall performance of the animals'motor behavior and the functional status of
      limb movements during bipedal locomotion were graded by the Combined Behavioral
      Score (CBS) system. Using the simple Allen weight-drop technique, a contusive
      injury was produced by dropping a 13-g weight from a height of 30 cm to the
      exposed spinal cord at the T12-L1 vertebral level of the trained monkeys. All the
      monkeys showed significant impairments in every reflex activity and in walking
      behavior during the early part of the postoperative period. In subsequent
      periods, the animals displayed mild alterations in certain reflex responses, such
      as grasping, extension withdrawal, and placing reflexes, which persisted through
      a 1-year follow-up. The contused animals traversed locomotor runways--narrow
      beam, incline plane, and grid runways--with more steps and few errors, as
      evaluated with the CBS system. Eventually, the behavioral performance of all
      spinal-contused monkeys recovered to near-preoperative level by the fifth
      postoperative month. The findings of this study reveal the recovery time course
      of various reflex components and bipedal locomotor behavior of spinal-contused
      macaques on runways for a postoperative period of up to 1 year. Our spinal cord
      research in primates is advantageous in understanding the characteristics of hind
      limb functions only, which possibly mimic the human motor behavior. This study
      may be also useful in detecting the beneficial effect of various donor tissue
      neuroprotective drugs on the repair of impaired functions in a bipedal primate
      model of spinal injury.

PMID- 18042965
TI  - Synergies in intra- and interpersonal interlimb rhythmic coordination.
AB  - The authors conducted two experiments that served as a test bed for applying the
      recently developed uncontrolled manifold (UCM) approach to rhythmic motor
      coordination, which has been extensively investigated from a coordination
      dynamics perspective. The results of two experiments, one investigating within
      person and one investigating between-persons rhythmic movement coordination,
      identified synergistic behaviors in both of those types of coordination. Stronger
      synergies were identified for in-phase than antiphase coordination, at the
      endpoints of the movement cycles compared with the midpoints, for movement
      frequencies closer to the intrinsic frequency of the coordinated limbs, and for
      within-person coordination. Frequency detuning did not weaken the strength of
      interlimb rhythmic coordination synergies. The results suggest the synergistic
      behavior captured by the UCM analysis may be identifiable with the strength of
      coupling between the coordinated limbs. The UCM analysis appears to distinguish
      coordination parameters that affect coupling strength from parameters that weaken
      coordination attractors.

PMID- 18042966
TI  - Cognitive models of apraxia and motor control: linking theories and methods
      across two complementary research domains.
AB  - Apraxia is a complex movement disorder that frequently occurs following left
      hemisphere stroke. Studies on patients with apraxia constitute an especially
      interesting body of literature for motor control researchers who seek to
      understand the cognitive mechanisms involved in the voluntary control of
      movement. Reciprocally, among apraxia researchers, great interest exists
      concerning the ways in which methods and theory from the field of motor control
      can be brought to bear in the clinical and empirical evaluation of this disorder.
      Here we will review representative evidence on the etiology, frequency, and
      assessment of apraxia, and suggest how research methods and theories from the
      field of motor control can be applied to, and also benefit from, a deeper
      understanding of apraxia. Parallels are proposed between the major cognitive
      models of apraxia and motor control to facilitate translation of terminology and
      concepts, and to enrich the emerging dialogue between these two complementary
      research domains.

PMID- 18042967
TI  - A systematic ecological model for adapting physical activities: theoretical
      foundations and practical examples.
AB  - This article proposes a theory- and practice-based model for adapting physical
      activities. The ecological frame of reference includes Dynamic and Action System
      Theory, World Health Organization International Classification of Function and
      Disability, and Adaptation Theory. A systematic model is presented addressing (a)
      the task objective, (b) task criteria, (c) limitation and enablement criteria,
      (d) performance errors, and (e) adaptation suggestions. Four individual case
      examples are described, referring to the conceptual model and depicting its use
      in various settings of physical activity, including physical education,
      rehabilitation, competition, and recreation.

PMID- 18042968
TI  - A test of self-determination theory with wheelchair basketball players with and
      without disability.
AB  - Guided by Self-Determination Theory (SDT), the present study examined the sport
      motivation and coping skills of male and female wheelchair basketball players
      with and without disability (N = 72). In line with SDT, results showed that
      intrinsic and extrinsic motivation as well as amotivation was found to be present
      in this sample of wheelchair basketball players. Results also demonstrated that
      the participants surveyed in the present study scored higher on self-determined
      types of motivation than non self-determined types of motivation, thus
      replicating past research with athletes without disability. Furthermore,
      wheelchair basketball players with and without disability did not differ
      significantly with respect to sport motivation and coping skills, suggesting that
      they are more alike than dissimilar. Finally, results revealed that self
      determined motivation is associated with enhanced psychological functioning.

PMID- 18042969
TI  - Shot trajectory parameters in gold medal stationary shot-putters during world
      class competition.
AB  - The parameters of the shot's trajectory were reported for male and female gold
      medalists (classes F52, F53, F54, and F55) who competed at the 2000 Paralympic
      Games and the 2002 International Paralympic Committee (IPC) World Championships.
      The specific objective was to determine the magnitude of differences in these
      parameters across classes and genders. The release velocity of the shot increased
      with the performance and the classification for both males (8.30 m/s - 9.96 m/s)
      and females (4.58 m/s - 8.50 m/s). The measured angle of the shot's trajectory at
      release also increased with the performance and the classification for both males
      (27.54 degrees - 32.47 degrees) and females (9.02 degrees - 34.52 degrees). The
      position of the shot from a fixed reference point at release revealed a similar
      trend for both males (2.01 m - 2.68 m) and females (1.16 m - 1.98 m), although it
      was weaker.

PMID- 18042970
TI  - Kinesthetic ability in children with spastic hemiplegia.
AB  - The purpose was to examine the differences in kinesthetic ability, at the elbow
      joint, between children with (n = 15) and without (n= 15) spastic hemiplegia. The
      Kin Com 125 AP isokinetic dynamometer Configuration Chattanooga was used. Results
      revealed significant (p < .05) interaction between participant groups and side
      which was a repeated measures factor (nonaffected side for CP group and dominant
      side for nonCP group vs. affected side for CP and nondominant side for nonCP
      group) with respect to the passive reproduction of movement (PRM) and detection
      of passive movement (DPM). The interaction was attributed to the kinesthetic
      deficits of the hemiplegic participants compared to the control group. A
      significant relationship was found between the level of spasticity and PRM
      scores.

PMID- 18042971
TI  - Older adults demonstrate reduced performance in a Fitts' task involving cervical
      spine movement.
AB  - A discrete aiming head movement task was developed to replicate Fitts'movement
      paradigm. Movement time (MT) differences between young (age range 24-29 years, n
      = 8) and old adults (age range 75-85 years, n = 8) were examined. Cervical spine
      (CS) range of motion (ROM) was recorded.A head mounted motion capture device was
      used to evaluate task performance. Three amplitudes and three target widths
      generated nine indexes of difficulty (IDs). Global ROM was decreased in old
      adults. The ID and MT relationship was maintained with age; however, old adults
      were slower, more variable, and more affected by ID. Variations in target size
      were used as the accuracy variable for both groups. As target size increased, the
      old population overshot their endpoint. These data support the hypothesis that,
      besides musculoskeletal slowing with age, there may be age-related deterioration
      of central processing, planning, or perception mechanisms.

PMID- 18042972
TI  - Adipogenesis in nonadherent and adherent bone marrow stem cells grown in fibrin
      gel and in the presence of adult plasma.
AB  - Bone marrow-derived mesenchymal stem cells (i.e., adherent cells) are known to
      differentiate into fat tissue in the presence of adipogenic supplements in
      cultures. Induction of adipogenesis has not been investigated within the
      nonadherent cell fraction that includes predominantly hematopoietic cells. In the
      present study, murine nonadherent bone marrow-derived stem cells (96% CD45+
      cells) were seeded and then grown in fibrin gel to form cell clusters in which
      most cells were positive to DiI-acetylated low-density lipoprotein uptake.
      Amongst different culture media supplemented either in fetal bovine serum, horse
      serum, murine plasma, human plasma or adipogenic supplements, a subpopulation of
      nonadherent stem cells within clusters differentiated into adipocytes,
      specifically in the presence of adult syngeneic plasma. This was confirmed by the
      observation and quantification of oil red O-positive cells, the measurement of
      glycerol-3-phosphate dehydrogenase activity and peroxisome proliferator-activated
      receptor-gamma mRNA expression. Similarly, adipogenesis was also observed in the
      presence of murine plasma with adherent mesenchymal stem cells and 3T3-L1
      preadipocytes which were grown either in monolayer plastic cultures or in fibrin
      gel. Thus, it is possible that nonadherent cells, once in a 3-dimensional
      environment, can further differentiate towards adipogenesis.

PMID- 18042973
TI  - Diversity of fibroblasts--a review on implications for skin tissue engineering.
AB  - Enormous advances in the development of skin substitutes have occurred in the
      past 3 decades. Major obstacles yet to be overcome in the quest for an optimal
      skin substitute include controlling scar formation, contraction and the loss of
      adnexal structures. Mesenchyme-derived signals are essential for epithelial
      proliferation, skin morphogenesis, homeostasis and differentiation. Having
      previously shown that fibroblasts differentiate along a lineage from highly
      proliferative progenitor fibroblasts with characteristic spindle-shaped
      appearance to differentiated postmitotic polygonal fibrocytes, we have now
      established that the different subsets of fibroblasts exert significantly
      different patterns of cytokine release and that the highest levels of
      keratinocyte growth factor and transforming growth factor-beta1 expression result
      from differentiated fibroblasts. Coculture studies with keratinocytes reveal that
      postmitotic fibroblasts stimulate keratinocyte proliferation to a greater extent
      than progenitor fibroblasts. Acellular and fibroblast-seeded dermal substitutes
      have been shown to improve scarring and contraction in animal studies, the latter
      substitutes yielding the most favorable results. Fibroblasts from different body
      sites display different functional properties which may affect their suitability
      for dermal substitutes. Future in vivo human studies in tissue-engineered dermal
      substitutes will likely focus on fibroblast-seeded lattices and the impact of
      fibroblast subpopulations and bone marrow-derived mesenchymal stem cells on
      dermal regeneration.

PMID- 18042974
TI  - Mouth breathing in obstructive sleep apnea prior to and during nasal continuous
      positive airway pressure.
AB  - BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) often complain
      of dryness of mouth and throat prior to and during nasal continuous positive
      airway pressure (nCPAP). It is believed that this is due to mouth breathing (MB).
      However, the association between mouth breathing and apneas/hypopneas and the
      effect of CPAP on MB has not been studied. OBJECTIVES: The purpose of the present
      study was, therefore, to assess the frequency and duration of episodes of MB
      prior to and during treatment with nCPAP. METHODS: MB was recorded prior to and
      during nCPAP with a closely fitting mouth mask connected to a pneumotachograph
      and nasal flow was measured via nasal prongs. MB episodes were expressed as the
      number of events divided by total sleep time x 60, to give the MB event index per
      hour of sleep. MB time divided by total sleep time x 60 was calculated in minutes
      to get the MB time index per hour of sleep. PATIENTS: Eleven male patients with
      OSAS (mean age 57.9 +/- 8.3 years, body mass index 30.2 +/- 3.8) were recruited
      to the study. RESULTS: Prior to nCPAP, the apnea/hypopnea index was 55.8 +/- 26
      and decreased during nCPAP to 8.0 +/- 3.4. The lowest SaO2 measured was 82.9 +/-
      4.7%, and increased to 87.5 +/- 2.7% under nCPAP. The mean nCPAP was 7.8 +/- 1.6
      cm H2O. MB event index per hour of sleep decreased from 35.2 +/- 19.7 prior to
      treatment to 5.0 +/- 5.2 under nCPAP (p < 0.01). In 52.2 +/- 27.4% of obstructive
      respiratory events, MB started at the end of an apnea/hypopnea episode,
      decreasing to 8.5 +/- 12.5% with nCPAP treatment. MB time index per hour of sleep
      was reduced from 13.5 +/- 10.2 min prior to treatment to 4.6 +/- 5.5 min under
      nCPAP (p < 0.05). CONCLUSIONS: In OSAS patients, MB episodes often appear at the
      termination of an apnea/hypopnea episode. In many cases, MB episodes can be
      markedly reduced by nCPAP treatment. When patients on nCPAP complain of dry
      mouth, appropriate measurements should be performed to verify MB.

PMID- 18042975
TI  - Efficacy of salbutamol and ipratropium bromide in the management of acute
      bronchiolitis--a clinical trial.
AB  - BACKGROUND: A wide range of drugs are commonly used to treat bronchiolitis, but
      evidence of their effectiveness is limited. OBJECTIVES: To investigate the
      efficacy of ipratropium bromide and salbutamol in the treatment of patients with
      moderate-severe bronchiolitis. METHODS: Sixty-nine infants with moderate-severe
      bronchiolitis hospitalized at their first episode of wheezing or crepitations in
      the chest were enrolled in a prospective, double-blind, placebo-controlled trial.
      Patients were randomly assigned to receive nebulized salbutamol, ipratropium
      bromide or placebo. Main outcome measures were changes in oxygen saturation rates
      and clinical scores and duration of hospitalization. RESULTS: In the
      bronchodilator groups, clinical scores were better compared to the placebo group
      at 30 min (8.4 +/- 1.3 vs. 7.5 +/- 0.8, p < 0.05). Bronchodilator groups had also
      significantly lower clinical scores (7.3 +/- 1.2 vs. 5.9 +/- 1.1, p < 0.0001, and
      5.3 +/- 1.4 vs. 4.5 +/- 1.6, p = 0.006, respectively) and higher oxygen
      saturation rates compared to the placebo group at 8 and 24 h (89.6 +/- 2.4 vs.
      94.3 +/- 4.4, and 92.2 +/- 2.6 vs. 95.9 +/-4.4, respectively, p < 0.0001).
      Improvement rates and duration of hospitalization were not statistically
      different among groups. CONCLUSIONS: Clinical scores and oxygen saturation levels
      improved more rapidly in the bronchodilator groups than in the placebo group up
      to 24 h, but these drugs did not have a sufficient effect to change the natural
      course of the disease.

PMID- 18042976
TI  - Chest physiotherapy in cystic fibrosis: short-term effects of autogenic drainage
      preceded by wet inhalation of saline versus autogenic drainage preceded by
      intrapulmonary percussive ventilation with saline.
AB  - BACKGROUND: Chest physiotherapy has been used for many years to assist in the
      removal of abnormal viscid bronchial secretions in cystic fibrosis (CF) patients.
      OBJECTIVES: This study compared the short-term effects of two physiotherapy
      regimens in patients with CF: autogenic drainage (AD) preceded by either saline
      inhalation ('saline(NEB) + AD') or by intrapulmonary percussive ventilation (IPV)
      with saline ('saline(IPV) + AD'). METHODS: In a randomized crossover design, 20
      clinically stable CF patients with similar pulmonary function at baseline
      received either 'saline(NEB) + AD' or 'saline(IPV) + AD' on 2 consecutive days.
      Transcutaneous oxygen saturation, heart rate, Borg dyspnea score and mucus wet
      weight were evaluated after 15 min of either saline(NEB) or saline(IPV), and
      after a subsequent 30 min of AD. RESULTS: There were no significant changes in
      oxygen saturation, heart rate or Borg score at any point of either physiotherapy
      intervention. There was no significant difference in sputum wet weight recovered
      with either saline(NEB) (2.2 +/- 1.8 g, mean +/- SD) or saline(IPV) (1.7 +/- 1.9
      g) alone. Subsequent AD did produce significantly greater amounts of sputum wet
      weight (p < 0.0001 for both) than in the initial saline delivery period, yet the
      amount of wet weight was similar irrespective of whether AD was preceded by
      saline(NEB) (9.7 +/- 6.5 g) or saline(IPV) (11.6 +/- 7.3 g). CONCLUSIONS:
      Recovered sputum weight is similar whether AD is preceded by saline(NEB) or
      saline(IPV). The much greater amount of mucus obtained during the AD period than
      during the saline delivery period warrants further investigation.

PMID- 18042978
TI  - Chronic obstructive pulmonary disease: a chronic systemic inflammatory disease.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by chronic
      inflammation in both the airways causing airway obstruction and the lung tissues
      causing emphysema. The disease is induced by inhalation of noxious gasses and
      particulate matter resulting in a chronic persistent inflammatory response in the
      lung, and the extent of the inflammatory reaction correlates with the severity of
      the disease. This chronic inflammatory response in the lung is also associated
      with a significant systemic inflammatory response with downstream adverse
      clinical health effects. The systemic response in COPD is associated with
      mortality, specifically cardiovascular mortality. This review describes the
      nature of the systemic inflammatory response in COPD and the clinical
      manifestations associated with the systemic response, with a focus on the
      potential mechanisms for these adverse health effects.

PMID- 18042977
TI  - Variability of exhaled breath condensate pH in lung transplant recipients.
AB  - BACKGROUND: Measurement of pH in exhaled breath condensate (EBC) may represent a
      novel method for investigating airway pathology. OBJECTIVES: The aim of this
      longitudinal study was to assess the variability of EBC pH in stable lung
      transplant recipients (LTR). METHODS: During routine clinical visits 74 EBC pH
      measurements were performed in 17 LTR. EBC pH was also measured in 19 healthy
      volunteers on four separate occasions. EBC pH was determined at standard CO2
      partial pressure by a blood gas analyzer. RESULTS: Mean EBC pH in clinically
      stable LTR and in controls was similar (6.38 +/- 0.09 vs. 6.44 +/- 0.16; p =
      nonsignificant). Coefficient of variation for pH in LTR and controls was 2.1 and
      2.3%, respectively. The limits of agreement for between-visit variability
      determined by the Bland-Altman test in LTR and healthy volunteers were also
      comparable (-0.29 and 0.46 vs. -0.53 and 0.44). CONCLUSIONS: Our data suggest
      that the variability of EBC pH in stable LTR is relatively small, and it is
      similar to that in healthy nontransplant subjects.

PMID- 18042979
TI  - Progressive stroke involving bilateral medial medulla expanding to spinal cord
      due to vertebral artery dissection.

PMID- 18042980
TI  - Spontaneous carotid artery dissection in a patient with Turner syndrome.

PMID- 18042981
TI  - USPIO-enhanced MRI of neuroinflammation at the sub-acute stage of ischemic
      stroke: preliminary data.

PMID- 18042982
TI  - The relationship between socioeconomic deprivation, atypical respiratory
      infections and survival outcome in elderly stroke and medical patients.

PMID- 18042983
TI  - Thrombolysis for acute stroke: what about the actual impact on patients older
      than 80 years?

PMID- 18042984
TI  - Effect of fluoride compounds on enamel erosion in vitro: a comparison of amine,
      sodium and stannous fluoride.
AB  - The aim of the study was to evaluate the relevance of cations in different
      fluoride compounds for their effectiveness as anti-erosive agents. Human enamel
      samples underwent a de- and re-mineralisation procedure for 10 days. Erosive
      demineralisation was performed with 0.05 M citric acid (pH 2.3) 6 x 2 min daily
      followed by immersion in the test solution 6 x 2 min each. Test solutions were:
      SnCl2 (815 ppm Sn; pH 2.6), NaF (250 ppm F; pH 3.5), SnF2 (250 ppm F, 809 ppm Sn;
      pH 3.5), amine fluoride (AmF, 250 ppm F; pH 3.5), AmF/NaF (250 ppm F; pH 4.3),
      and AmF/SnF2 (250 ppm F, 390 ppm Sn; pH 4.2). In the control group no
      fluoridation was performed. Mineral content was monitored by longitudinal
      microradiography. Finally, scanning electron microscopy was performed. The
      highest erosive mineral loss was found in the control group (48.0 +/- 17.1
      microm). Mineral loss was nearly completely inhibited by AmF/SnF2 (5.7 +/- 25.1
      microm; p < or = 0.001) and SnF2 (-3.8 +/- 14.4 microm; p < or = 0.001)
      treatments. Groups treated with SnCl2 (17.6 +/- 19.5 microm; p < or = 0.001) and
      NaF (13.2 +/- 21.7 microm; p < or = 0.001) showed a decrease in erosive mineral
      loss, AmF (41.6 +/- 16.0 microm) and AmF/NaF (27.7 +/- 28.4 microm) had no
      significant effect on erosion progression. The results indicate considerable
      differences between the fluoride compounds tested. Treatment with solutions
      containing SnF2 was most effective.

PMID- 18042985
TI  - Dental findings in diabetic adults.
AB  - The dental status of dentate diabetic adults (n = 299) and its associations with
      diabetes-related factors was explored in Tehran, Iran. Presence of diabetes
      related complications made no difference in mean values of DMFT, but was
      associated with a higher number of decayed and missing teeth, and fewer filled
      teeth. Higher level of HbA1c was associated with higher DMFT for men, but not for
      women. In conclusion, the results suggest a possible association between the
      level of metabolic control of diabetes mellitus and cumulative caries experience.

PMID- 18042986
TI  - Effects of amine fluoride on biofilm growth and salivary pellicles.
AB  - The amine fluoride (AmF) N'-octadecyl-trimethylene-diamine-N,N,N'-tris(2-ethanol)
      dihydro-fluoride is a cationic antimicrobial which can have beneficial effects on
      plaque formation. Here, we determine changes in pellicle and bacterial cell
      surface properties of the strains Actinomyces naeslundii HM1, Streptococcus
      mutans NS, S.mutans ATCC 700610, S. sobrinus HG1025 and S. oralis HM1 upon
      adsorption of this AmF and accompanying effects on bacterial adhesion and biofilm
      growth. In vitro pellicles had a zeta potential of -12 mV that became less
      negative upon adsorption of AmF. The chemical functionalities in which carbon and
      oxygen were involved changed after AmF adsorption and AmF-treated pellicles had a
      greater surface roughness than untreated pellicles. Water contact angles in vitro
      decreased from 56 to 45 degrees upon AmF treatment, which corresponded with water
      contact angles (44 degrees ) measured intraorally on the front incisors of
      volunteers immediately after using an AmF-containing toothpaste. All bacterial
      strains were negatively charged and their isoelectric points (IEP) increased upon
      AmF adsorption. Minimal inhibitory concentrations were smallest for strains
      exhibiting the largest increase in IEP. Adhesion to salivary pellicles and
      biofilm growth of the mutans streptococcal strains were significantly reduced
      after AmF treatment, but not of A. naeslundii or S. oralis. However, regardless
      of the strain involved, biofilm viability decreased significantly after AmF
      treatment. The electrostatic interaction between cationic AmF and negatively
      charged bacterial cell surfaces is pivotal in establishing reduced biofilm
      formation by AmF through a combination of effects on initial adhesion and
      killing. The major effect of AmF treatment, however, was a reduction brought
      about in biofilm viability.

PMID- 18042987
TI  - Low-fluoride dentifrice and caries lesion control in children with different
      caries experience: a randomized clinical trial.
AB  - Since there is no consensus on the anticaries effectiveness of low-fluoride (F)
      dentifrice, this randomized clinical trial evaluated its effect in children at
      different caries activity status. One hundred and twenty 2- to 4-year-old
      children, half with and half without active caries lesions, were randomly divided
      into 2 groups which used 500- or 1,100-microg F/g (NaF) dentifrices during 1
      year. Caries progression or regression were evaluated as the number of lesions
      becoming active/cavities or inactive, respectively. The anticaries effect of the
      low-F dentifrice was similar to the conventional F dentifrice when used by caries
      inactive children. However, in children with active caries lesions the low-F
      dentifrice was less effective than the 1,100-microg F/g dentifrice in controlling
      the progression of lesions. The data suggest that the child caries activity may
      be taken into account to recommend a low-F dentifrice.

PMID- 18042989
TI  - Oral hygiene and parent-related factors during early childhood in relation to
      approximal caries at 15 years of age.
AB  - The aim was to investigate whether oral hygiene habits and parent-related
      factors, recorded in early childhood, have a predictive value in relation to
      approximal caries experience (including initial caries lesions) at the age of 15
      years (n = 568). Data were selected from examinations, interviews and
      questionnaires at 1 and 3 years and bitewing radiographs at 15 years. Four levels
      of cut-off points for the statistical analysis were used: DFa = 0, > 0, > or = 4
      and > or = 8. In the final logistic regression analyses, mother's self-estimation
      of her oral health care being less good remained statistically significant and
      predicted a caries experience of DFa > 0 at 15 years. The following four
      variables predicted DFa > or = 4: (1) female gender, (2) plaque on maxillary
      incisors at 1 year, (3) mother's self-estimation of her oral health care being
      less good and (4) father being less satisfied with his social situation. Two
      variables predicted DFa > or = 8: (1) toothbrushing with fluoride toothpaste just
      once a day, and (2) father being less satisfied with his social situation.
      Furthermore, children who failed to attend the examination at 1 year of age had
      6.95 +/- 5.36 (mean +/- SD) DFa at 15 years compared with 3.10 +/- 3.85 for
      children who were examined at 1 year of age (p < 0.01). To conclude, factors
      explaining good dental health at 15 years of age pertained to both children and
      parents. Thus, it seems that good oral hygiene habits, established in early
      childhood, provide a foundation for a low experience of approximal caries in
      adolescents.

PMID- 18042988
TI  - Possible association of amelogenin to high caries experience in a Guatemalan
      Mayan population.
AB  - There is evidence for a genetic component in caries susceptibility, but the
      disease is greatly influenced by environmental factors, which are extremely
      difficult to control in humans. For the present study, we used DNA samples
      collected from 110 unrelated, non-cleft individuals older than 12 years of age
      from Tiquisate, Guatemala: a population with similar cultural, dietary and
      hygiene habits, similar access to the dentist and fluoride exposure. Forty-four
      individuals were designated 'very low caries experience' (DMFT < or = 2), and 66
      were designated 'higher caries experience' (DMFT > or = 3). Single-nucleotide
      polymorphism markers were genotyped in selected candidate genes (ameloblastin,
      amelogenin, enamelin, tuftelin-1, and tuftelin interacting protein 11) that
      influence enamel formation. Having at least one copy of the rare amelogenin
      marker allele was associated with increased age-adjusted caries experience. This
      association was stronger in individuals with higher DMFT (DMFT > or = 20; p =
      0.0000001). Our results suggest that variation in amelogenin may contribute to
      caries susceptibility in the population studied. The approach of comparing
      individuals with extremely distinct caries experiences could be valuable for
      decreasing the potential influence of environmental factors on genetic studies of
      caries.

PMID- 18042990
TI  - Influence of salivary macromolecules and fluoride on enamel lesion
      remineralization in vitro.
AB  - The aim of this study was to investigate the influence of salivary macromolecules
      on enamel lesion remineralization in the presence or absence of fluoride.
      Paraffin-stimulated whole saliva was centrifuged, and the supernatant was
      dialyzed in 1,000 molecular-weight cutoff dialysis tubes, first against a
      phosphate buffer and then against a mineral solution containing Ca and phosphate.
      Artificial subsurface lesions of human enamel, created in pH 4.5 acetate buffer,
      were remineralized for 28 days in 4 remineralizing solutions: group C--mineral
      solution as a control; group S--mineral solution + dialyzed saliva; group F-
      mineral solution + 1 ppm F; group SF--mineral solution + dialyzed saliva + 1 ppm
      F. Changes in relative mineral concentration in the lesions were assessed by
      transverse microradiography. The results showed statistically significant mineral
      gains in the lesion body in groups C (DeltaZ = 3,254 +/- 1,562% x microm) and SF
      (DeltaZ = 2,973 +/- 1,349% x microm), but not in groups S (DeltaZ = 5,192 +/-
      1,863% x microm) and F (DeltaZ = 4,310 +/- 1,138% x microm) compared with the
      baseline group (DeltaZ = 5,414 +/- 461% x microm). It was also found that the
      mineral density at the surface layer in group F (75.0 +/- 15.7%) was greater than
      that in the baseline group (30.1 +/- 12.3%) with statistical significance, but
      not in group SF (39.9 +/- 16.5%). It was concluded that the macromolecules
      inhibited lesion remineralization fundamentally but that these molecules, in the
      presence of fluoride, seemed to play an important role in the continuation of
      remineralization by reducing mineral gains at the surface layer.

PMID- 18042991
TI  - Dentine remineralization by simulated saliva formulations with different Ca and
      Pi contents.
AB  - The understanding of the dentine remineralization process and the ability to
      reproduce it in vitro are essential to the development of preventive and
      therapeutic measures. This study investigated how simulated saliva formulations
      with different Ca and P(i) contents and degrees of saturation with respect to
      biologically relevant calcium phosphates may affect the remineralization of
      eroded dentine, as a function of time. Slabs of bovine root dentine (n = 8 per
      group) were flattened, polished, demineralised by 1% citric acid for 30 and 60
      min and remineralized for 3, 7 and 14 days, by one of the following buffered (pH
      7) solutions [Ca:Pi ratio, Ca/Pi concentrations (mM), ionic strength]: solution
      A: 1.6, 1.5/0.9, 0.115; solution B: 1.6, 2/1.25, 0.117; solution C: 1.6, 3.2/2,
      0.121; solution D: 0.3, 1.11/3.7, 0.118; solution E: 0.3, 1.45/5, 0.122.
      Integrated mineral loss (30 and 60 min) was quantified by transverse
      microradiography after each remineralization period. ANOVA and regression
      analyses (alpha = 0.05) showed, irrespective of the demineralisation time, that
      the solutions C and E were able to remineralize dentine. This effect increased
      throughout the remineralization times and was significantly higher for E.
      Remineralization was successfully shown in vitro, under specific conditions of
      degree of saturation and Ca and Pi contents of the solutions. Optimum
      remineralization was observed for the solution E supersaturated with respect to
      relevant calcium phosphates, with low Ca:Pi ratio and highest Pi concentration.

PMID- 18042992
TI  - Neuroimaging predictors of cognitive impairment in confluent white matter lesion:
      volumetric analyses of 99 brain regions.
AB  - BACKGROUND: Although confluent white matter lesion (WML) is associated with
      cognitive impairment, the mechanism explaining this association is controversial.
      We aimed to investigate comprehensively the MRI predictors of cognitive
      impairment in confluent WML. METHODS: Among 45 lacunar stroke patients who had
      confluent WML, we evaluated the association of executive function [Mattis
      Dementia Rating Scale - Initiation/Perseveration subscale (MDRS I/P)] and global
      cognition [Mini-Mental State Examination (MMSE)] with the volume of WML, measures
      of lacunes and microbleeds, and the volumes of 99 other specific brain regions.
      RESULTS: Regression analyses showed that WML volume predicted performance on the
      MDRS I/P (beta = -0.34, p = 0.016) independent of age. Volumes of cortical gray
      matter (cGM; beta = 0.41, p = 0.003), the lateral fronto-orbital gyrus (beta =
      0.38, p = 0.01), superior frontal gyrus (beta = 0.29, p = 0.04), lateral
      ventricle (beta = -0.30, p = 0.04), and posterior limb of the internal capsule
      (beta = 0.43, p = 0.002) predicted MDRS I/P performance independent of WML
      volume. Volumes of cGM, and the lateral fronto-orbital gyrus predicted MMSE
      performance as well. CONCLUSION: Atrophy along the frontosubcortical pathways and
      cGM predict cognition in confluent WML independent of WML volume.

PMID- 18042993
TI  - Cognitive decline and survival in Alzheimer's disease according to education
      level.
AB  - OBJECTIVE: We tested the hypothesis that a higher education level is associated
      with faster cognitive decline and lower survival in a cohort of 670 Alzheimer's
      disease patients, followed for 3.5 years at the Lille-Bailleul memory centre.
      METHODS: The patients were categorized in 3 groups according to educational
      levels: low (<or=8 years), intermediate (9-12 years) and high (>12 years).
      Cognitive function was measured with the Mini Mental State Examination (MMSE) and
      the Mattis Dementia Rating Scale (DRS). Survival was analyzed with a Cox model.
      Analyses were adjusted for age, sex, cholinesterase inhibitor treatment,
      diabetes, hypertension, visible vascular lesions on MRI, baseline DRS and MMSE.
      RESULTS: The adjusted mixed random model showed that MMSE declined faster for
      patients with high and intermediate educational levels compared with those with a
      low educational level (p < 0.0001). The mean annually adjusted DRS decline was
      highest for the groups with the most education (p = 0.05). The mortality risk was
      not higher in the better-educated groups (high vs. low: RR = 0.84; 95% CI = 0.35
      1.99, intermediate vs. low: RR = 0.82; 95% CI = 0.41-1.63). CONCLUSION: In our
      cohort, highly educated patients had a faster cognitive decline than less
      educated patients but similar mortality rates. Our findings support the cognitive
      reserve hypothesis.

PMID- 18042994
TI  - Relationship between measures of dementia severity and observation of daily life
      functioning as measured with the Assessment of Motor and Process Skills (AMPS).
AB  - BACKGROUND: Cognitive impairment is mostly regarded as the core symptom of
      dementia, but several other domains (such as daily functioning) are equally
      relevant to assess the severity of dementia. The relationship between these
      domains is unclear. The Assessment of Motor and Process Skills (AMPS) is a
      relatively unexplored instrument in people with dementia, measuring severity by
      direct observation. OBJECTIVE: To study the relationship between the AMPS and
      scores on several commonly used outcome measures for the assessment of dementia
      severity, and to examine the possible influence of neuropsychiatric symptoms on
      these relationships in patients with cognitive disorders. METHODS: Cross
      sectional data of 118 patients with cognitive disorders were used; data on
      cognition (Mini-Mental State Examination, MMSE; CAMCOG), global severity (Global
      Deterioration Scale, GDS), daily life functioning (Instrumental Activities of
      Daily Living, IADL), and neuropsychiatric symptoms (Neuropsychiatric Inventory,
      NPI) were collected and analyzed using correlation and regression analyses.
      Different combinations of the severity measures were tested for their ability to
      predict the AMPS process ability scores. RESULTS: Scores on the MMSE, CAMCOG and
      GDS were moderately associated with the AMPS process ability score. These
      measures explained between 27 and 44% of the variance in the AMPS score. The
      presence of apathy influenced the association between the cognitive measures and
      the AMPS score. CONCLUSION: Commonly used measures of dementia severity are only
      moderately associated with observation of performance on daily activities. This
      underlines the need for direct observation of daily activities in dementia
      patients. This relationship between several approaches of assessing dementia
      severity needs further study.

PMID- 18042995
TI  - Pregnancy outcomes following bipolar umbilical cord cauterization for selective
      termination in complicated monochorionic multiple gestations.
AB  - OBJECTIVE: To review pregnancy and childhood outcomes following selective
      termination by ultrasound guided bipolar umbilical cord cauterization (UCC) in
      complicated monochorionic multifetal pregnancies. STUDY DESIGN: Consenting
      patients (27 of 49, 55%) had review of pregnancy history and pediatric
      development in the surviving twin following selective UCC. RESULTS: UCC was
      performed at 21.2 +/- 2.8 weeks gestational age, followed by a liveborn delivery
      (n = 28) at 34.4 +/- 4.7 weeks. Mean birth weight was 2,218 +/- 926 g.
      Complications included preterm labor (25.0%), premature rupture of membranes
      (17.8%), placental abruption (10.7%) and chorioamnionitis (7.1%). Perinatal
      mortality was 10.3% in continuing fetuses. However, 96.2% of pregnancies achieved
      livebirths with 96% of neonates showing apparently normal development between
      ages 1.5 and 5 years. CONCLUSION: Bipolar UCC is a reasonably safe and effective
      treatment for selective termination in complicated monochorionic pregnancies.

PMID- 18042996
TI  - Blood pressure and cognition in the Aberdeen 1936 birth cohort.
AB  - BACKGROUND: The relationship between blood pressure and cognition in old age
      remains unclear. Some data indicate that elevated blood pressure causes cognitive
      deficits whilst others show that lower early life mental ability predicts high
      blood pressure in adulthood. Longitudinal studies in which mental ability earlier
      in life is known are needed to clarify the relationship. OBJECTIVE: To measure
      the effect of blood pressure on cognition in late adulthood after adjusting for
      early life mental ability. METHODS: The sample comprised survivors of the 1947
      Scottish Mental Survey who had validated IQ scores at age 11. Six cognitive tests
      - Mini-Mental State Examination, Raven's Progressive Matrices, Rey Auditory
      Verbal Learning Test, Uses of Common Objects Test, Digit Symbol Test and Block
      Design - were administered at ages 64, 66 and 68 years. Sitting and standing
      blood pressure was also measured at each wave of follow-up. Mixed general linear
      models were constructed with each cognitive test treated as a repeated measure of
      an underlying cognitive trait and with wave of testing also set as a repeated
      measure. Mental ability at age 11 was entered as a covariate. RESULTS: 504
      participants were tested at wave 1 with 368 returning at wave 2 and 300 at wave
      3. Age 11 mental ability did not predict any of the blood pressure measures.
      There were several significant associations between blood pressure variables and
      cognitive test scores in univariate models. After adjusting for significant
      effects of wave of testing, type of cognitive test, the interaction between
      these, age 11 mental ability, age, gender and occupation in a multivariate model,
      the main effect of BP trait was no longer significant (p = 0.44) nor its effect
      over time (p = 0.26), though there was a significant interaction between blood
      pressure trait (BP) and test type with a distinctly negative effect of BP on
      Auditory Verbal Learning Test (p = 0.007, -0.13 points per mm Hg higher, 95% CI 
      0.22 to -0.033). CONCLUSION: The effects of blood pressure on cognition in old
      age are finely nuanced. Multivariate repeated measures models reveal a
      differential effect of blood pressure on verbal recall.

PMID- 18042997
TI  - Neurological disorders in Libya: an overview.
AB  - The aim of this study was to review all publications related to the incidence and
      prevalence of neurological disorders in Libya, and to estimate the burden of
      these disorders in the country. The PubMed and the Libyan Medical Index were
      searched using different combinations of keywords. The references in all relevant
      papers were reviewed for any additional publications. An estimation of the number
      of patients with neurological disorders was made based on the reviewed data and
      adjusted using the Libyan Nationwide Official Census of 2006. Sixteen papers were
      identified. Incidence rate is available for twelve disorders and the prevalence
      rate for nine. Data for some of the most common neurological problems such as
      headaches, or for important disorders such as dementia, are lacking. Therefore,
      the estimate of 6,892 new neurological cases per year and a total of 11,908
      neurological patients in 2006 in Libya is largely underestimating the burden of
      the neurological disorders in this country and should be regarded as the lowest
      possible estimation. Further neuroepidemiological studies in Libya are needed.

PMID- 18042998
TI  - The accuracy of prevalence rates of multiple sclerosis: a critical review.
AB  - Review of the recent medical literature raises doubts about the reliability of
      reported prevalence rates of multiple sclerosis (MS). Many published prevalence
      rates are inflated. Some studies have shown that relying on clinical information
      and MRI interpretation leads to one third of incorrect MS diagnoses. The most
      important error is failing to distinguish between the clinical and MRI
      characteristics of MS and of disseminated encephalomyelitis (DEM) in both their
      acute and relapsing forms. The diagnostic criteria in current usage, including
      those relating to imaging, do not differentiate between MS and other recurrent
      inflammatory demyelinating diseases of the central nervous system. Considering a
      second demyelinating episode following a clinically isolated symptom or acute
      DEM, as confirming MS, is another major source of error. Another is including
      cases with onset before they entered the study group or moved to the geographic
      area. Neuromyelitis optica (NMO) has long been considered an MS variant and in
      Far Eastern countries it is counted as the 'oriental' form of MS, falsely
      inflating prevalence rates of MS in those areas. Recent immunologic and
      radiologic evidence shows that at least some NMO cases represent instances of
      DEM.

PMID- 18042999
TI  - Gait speed predicts decline in attention and psychomotor speed in older adults:
      the health aging and body composition study.
AB  - BACKGROUND/AIMS: Gait speed is cross-sectionally associated with attention and
      psychomotor speed in older community dwellers. It is unclear if gait speed
      predicts decline in these cognitive domains over time. METHODS: Usual gait speed
      (m/s) over 6 m was measured at baseline in 2,776 Health, Aging and Body
      Composition Study participants (mean age +/- SD 73.5 +/- 2.8 years, 53% women,
      37% blacks). The Digit Symbol Substitution Test (DSST) was administered at
      baseline and after 5 years to assess attention and psychomotor speed. We used
      multivariate logistic regression models to calculate the risk of DSST 5-year
      decline [>1 SD from mean change (9 points)] across quartiles of gait speed,
      adjusting for demographics, weight, physical activity, comorbidities, depression
      and Modified Mini-Mental State Examination. RESULTS: After 5 years, 389 (17.1%)
      participants declined in DSST. Compared to those in the highest quartile of gait
      speed (>1.35 m/s), participants in the lowest quartile (<1.05 m/s) were more
      likely to decline in DSST independently of the considered covariates (OR 1.74,
      95% CI 1.21-2.51, adjusted p for trend across quartiles = 0.006). CONCLUSIONS: In
      this cohort of older community dwellers, gait speed independently predicted a
      decline in DSST after 5 years.

PMID- 18043000
TI  - The management approaches to dyskinesia vary from country to country.
AB  - Many Parkinson's disease (PD) patients treated with levodopa develop motor
      fluctuations and/or dyskinesia. This large, retrospective study was conducted to
      compare the prevalence and treatment of dyskinesia in PD patients in seven
      countries. A total of 380 physicians were interviewed and completed patient
      record forms retrospectively for their last 5 patients with dyskinesia (total
      1,900). The overall prevalence of dyskinesia in PD patients was 34%, but the rate
      varied from 24 to 51% according to geographical location. This study showed that
      51.0% of Japanese physicians and 50.6% of UK physicians were dissatisfied with
      current treatment strategies for dyskinesia. Regardless of geographical location,
      physicians were dissatisfied with the current treatment strategies for
      dyskinesia.

PMID- 18043001
TI  - Mediterranean diet and essential tremor. A case-control study.
AB  - BACKGROUND: Higher adherence to the Mediterranean diet (MeDi) has been related to
      lower Alzheimer's disease risk. Some dietary factors have been studied in
      patients with essential tremor (ET), but the MeDi's effect has not been
      investigated. METHODS: Adherence to the MeDi was calculated from a food frequency
      questionnaire administered in a case-control study of environmental epidemiology
      of ET in the New York Tri-State area. Logistic regression models were used to
      examine whether adherence to the MeDi predicted ET (vs. control) outcome. The
      models adjusted for age, gender, ethnicity, education, caloric intake, body mass
      index, smoking, ethanol consumption, coffee intake and blood harmane
      concentrations. RESULTS: 148 ET cases adhered less to MeDi (0-9 scale with higher
      scores indicating higher adherence) than 250 controls (mean 4.3 +/- 1.7 vs. 4.7
      +/- 1.7; p = 0.03). Higher adherence to MeDi was associated with lower odds for
      ET [0.78 (0.61-0.99); p = 0.042]. As compared to subjects at the lowest MeDi
      adherence tertile, those at the middle tertile had lower ET odds [0.41 (0.16
      1.05)], while subjects at the highest tertile had an even lower ET odds [0.29
      (0.10-0.82); p for trend 0.021]. CONCLUSIONS: Compared to controls, ET cases
      adhered less to MeDi. The gradual reduction in ET odds with higher MeDi adherence
      tertiles suggests a possible dose-response effect. The mechanisms that underlie
      this association merit further study.

PMID- 18043002
TI  - Risks of subarachnoid hemorrhage in siblings: a nationwide epidemiological study
      from Sweden.
AB  - This nationwide study aimed to enhance available data by determining sibling
      risks of subarachnoid hemorrhage in a total population. The MigMed database at
      the Karolinska Institute, Stockholm, was used to identify all cases of
      subarachnoid hemorrhage diagnosed in Sweden between 1987 and 2001. Incidence
      ratios standardized for age, region, and socioeconomic status (SIRs) were
      calculated for persons with at least 1 sibling with subarachnoid hemorrhage. The
      reference group consisted of persons whose siblings had no subarachnoid
      hemorrhage. A total of 90 affected siblings were identified; their SIR of
      subarachnoid hemorrhage was 2.75. The risk decreased with increasing age in both
      men and women. Within the limits of the sample size, no sex differences could be
      observed. The relatively high sibling risks are likely to be due to heritable
      causes and shared environmental factors. Genetic causes possibly weigh more in
      early- than late-onset cases. This study shows the feasibility of carrying out
      nationwide family studies on subarachnoid hemorrhage.

PMID- 18043003
TI  - A case-control study of the environmental risk factors for narcolepsy.
AB  - BACKGROUND: Despite the acknowledged importance of environmental risk factors in
      the etiology of narcolepsy, there is little research on this topic. This study
      sought to fill this gap in the literature and assess the risk of stressors and
      infectious diseases using a case-control study. METHODS: Cases (n = 63) were
      recruited through the Stanford Center for Narcolepsy. All were HLA-DQB1*0602
      positive, met conventional Multiple Sleep Latency Test criteria, and reported
      unambiguous cataplexy. Controls (n = 63) were nonrelated family members of cases
      and local community members. A self-administered questionnaire was used to assess
      the frequency and timing of possible risk factors. RESULTS: Of the infectious
      diseases examined, only flu infections and unexplained fevers carried a
      significant risk. Several of the stressors carried a significant risk including a
      major change in sleeping habits. When the timing of all risk factors was
      considered, exposure prior to puberty increased the risk for developing
      narcolepsy. CONCLUSIONS: These findings emphasize the importance of environmental
      risk factors in the etiology of narcolepsy. This highlights the need for further
      research on this aspect of narcolepsy so a complete understanding of a disorder
      that affects 1 in 2,000 individuals can emerge.

PMID- 18043004
TI  - Gait variability is associated with subclinical brain vascular abnormalities in
      high-functioning older adults.
AB  - BACKGROUND: Gait variability is an index of how much gait parameters, such as
      step length, change from one step to the next. Gait variability increases with
      age and in individuals affected by cortical and subcortical neurodegenerative
      conditions, and it is associated with falls and incident mobility disability. The
      brain anatomical correlates of gait variability have not been studied in high
      functioning community-dwelling older adults. METHODS: Gait variability and brain
      MRIs were assessed in a cohort of 331 men and women (mean age = 78.3 years) free
      from stroke, dementia or Parkinson's disease. Gait variability was computed for
      spatial parameters (step length and step width) and for temporal parameters
      (stance time). Subclinical brain vascular abnormalities were measured on brain
      MRIs as infarcts and white matter hyperintensities. RESULTS: Greater variability
      of step length was associated with greater prevalence of infarcts, including
      infarcts in the basal ganglia, and with greater white matter hyperintensities
      severity, independent of age, gender, cognitive function and cardiovascular
      disease. Weaker associations were found between the other variability measures
      and the MRI measures. CONCLUSION: In this group of older adults free from
      neurodegenerative diseases, a greater variability of step length was associated
      with greater burden of subclinical brain vascular abnormalities as defined by
      MRI.

PMID- 18043005
TI  - Lipid-lowering agents and the risk of cognitive impairment that does not meet
      criteria for dementia, in relation to apolipoprotein E status.
AB  - Lipid-lowering agents (LLAs) might lower the risk of dementia, but any impact on
      other forms of cognitive impairment is not clear. We examined LLAs in relation to
      cognitive impairment, no dementia (CIND) and apolipoprotein E4 status. In a case
      control study from the Canadian Study of Health and Aging, cases (n = 347) had
      developed CIND between the first and second study waves and controls (n = 693)
      had no cognitive impairment at either time. LLA use was associated with a lower
      odds of incident CIND in those <80 years of age (OR 0.37; 95% CI 0.15-0.93) but
      not for those aged >or=80 years (OR 0.56; 95% CI 0.15-2.10). The reduced risk was
      significant for statins but not for other LLAs. Adjusting for apolipoprotein E4
      status did not change the point estimates of the ORs. The greatest impact of LLAs
      was seen in the CIND subtype circumscribed memory impairment.

PMID- 18043006
TI  - Does age of onset in essential tremor have a bimodal distribution? Data from a
      tertiary referral setting and a population-based study.
AB  - BACKGROUND/AIMS: The distribution of age of onset of essential tremor (ET) is
      unclear, with discrepancies in the literature. Some data suggest a bimodal
      distribution and other data 1 late-life peak. We studied age of ET onset in 2
      distinct settings: a population-based study and a tertiary referral center.
      METHODS: Age of onset data were collected. RESULTS: In the population, there was
      only a small peak at the age of <or=30 years (14.1% of cases) but a clear peak in
      later life (85.9% of cases). In the tertiary referral center, a bimodal
      distribution was apparent with 1 large peak (42.2% of cases) at the age of <or=40
      years and the second large peak (57.8% of cases) in later life. Familial cases
      accounted for only 52.6% of young-onset cases from the population, yet 82.7% from
      the tertiary center. DISCUSSION: In the population-based study, a peak in later
      life was clearly present but a young-onset peak was barely discernable,
      comprising few cases. By contrast, in a tertiary referral center, age of onset
      was clearly bimodal. While age of ET onset is often said to be bimodal, this may
      be due to the preferential referral to tertiary centers of patients with young
      onset, familial ET.

PMID- 18043007
TI  - The role of angiotensin II receptor-1 blockade in the hypoxic pulmonary
      vasoconstriction response in newborn piglets.
AB  - BACKGROUND: Angiotensin-converting enzyme activity is increased in newborn
      infants with respiratory distress syndrome and in animals with alveolar hypoxia.
      OBJECTIVE: To test whether angiotensin II (Ang II) mediates the pulmonary
      vasoconstriction induced by acute hypoxia in newborn piglets. METHODS: Eight
      unanesthetized chronically instrumented newborn piglets (mean +/- SEM; age 6.6 +/
      0.6 days; weight 2,181 +/- 174 g) were randomly assigned to receive a saline
      solution or the Ang II type 1 receptor (AT(1)) antagonist, losartan, in a
      crossover study design, with an interval of at least 48 h between the first and
      second study. Pulmonary artery (Ppa), wedge, systemic arterial (Psa) and right
      atrial pressures, cardiac output (CO), pulmonary (PVR) and systemic (SVR)
      vascular resistances, and arterial blood gases were obtained in room air, before
      and during the saline or losartan infusion (6 mg/kg followed by 3 mg/kg/h), and
      during 6 h of hypoxia (FiO(2) = 0.11) and saline or losartan infusion. Data were
      analyzed by repeated measures analysis of variance. RESULTS: The pulmonary
      vasoconstriction induced by acute hypoxia was significantly attenuated during
      losartan infusion, while Psa, SVR, CO, pH, PaCO(2), PaO(2) and base excess did
      not differ between groups. During room air, Ppa, PVR, Psa, SVR and CO values were
      not modified by saline or losartan infusion. CONCLUSION: These data suggest that
      the pulmonary vasoconstriction induced by acute hypoxia in newborn piglets is
      partially mediated by Ang II, acting via AT(1).

PMID- 18043008
TI  - New techniques in lacrimal gland research: the magic juice and how to drill for
      it.

PMID- 18043009
TI  - S-ibuprofen effectively inhibits thromboxane B2 levels and platelet function in
      an experimental model of lipopolysaccharide-stimulated and non-stimulated whole
      blood.
AB  - OBJECTIVE: The present study aimed at testing the effect of S- and R-ibuprofen on
      thromboxane B(2) (TXB(2)), collagen-epinephrine closure time (CEPI-CT) and
      collagen-adenosine 5'-diphosphate closure time (CADP-CT) in lipopolysaccharide
      (LPS)-stimulated and non-stimulated human whole blood. MATERIALS AND METHODS:
      Whole blood was incubated with S- or R-ibuprofen with and without prior
      stimulation with LPS. To verify ibuprofen's potential effects on TXB(2), varying
      ratios of concentrations of S- and R-ibuprofen ranging from 0 to 100% were used.
      TXB(2) levels were measured by ELISA. The effects of S- and R-ibuprofen
      enantiomers on platelet aggregability were tested utilizing a PFA-100 apparatus.
      RESULTS: In non-stimulated and LPS-stimulated whole blood, S-ibuprofen markedly
      decreased TXB(2) levels at concentrations ranging from 10 to 200 microg/ml. R
      ibuprofen showed its inhibiting effect at concentrations >100 microg/ml. In
      inflammatory and non-inflammatory conditions, CEPI-CT was prolonged at
      concentrations of 12.5 and 75 microg/ml for S-ibuprofen and at a concentration of
      150 microg/ml of combined R- and S-ibuprofen. S-ibuprofen was significantly more
      effective than R-ibuprofen (p < 0.05). The combined use of S- and R-ibuprofen did
      not additively or synergistically prolong CEPI-CTs. CADP-CTs remained unaffected
      by both enantiomers. CONCLUSIONS: S-ibuprofen was more effective than the R
      ibuprofen enantiomer in inhibiting TXB(2) plasma levels and aggregability of
      thrombocytes in non-inflammatory and inflammatory conditions.

PMID- 18043010
TI  - Repeated administration of histamine improves memory retrieval of inhibitory
      avoidance by lithium in mice.
AB  - The influence of repeated administration of histamine on lithium-induced state
      dependency has been investigated. A single-trial step-down inhibitory avoidance
      task was used to assess memory in adult male NMRI mice. Intraperitoneal (i.p.)
      administration of lithium (10 mg/kg), immediately after training (post-training),
      impaired inhibitory avoidance memory on the test day. Pre-test administration of
      lithium reversed amnesia induced by the drug given after training, with the
      maximum response at a dose of 10 mg/kg. Repeated intracerebroventricular (i.c.v.)
      administration of histamine (20 microg/mouse) for 3 consecutive days followed by
      5 days of no drug treatment improved memory retrieval of inhibitory avoidance by
      a pre-test lower dose (5 mg/kg i.p.) of lithium. In contrast, 3 days of i.c.v.
      injections of both the histamine H1 receptor antagonist pyrilamine (40
      microg/mouse) and the histamine H2 receptor antagonist ranitidine (6.25 and 12.5
      microg/mouse) prevented the improving effect of pre-test lithium (10 mg/kg i.p.)
      on memory retrieval. The results suggest that the repeated administration of
      histaminergic agents may induce a sensitization which affects the memory
      impairment induced by lithium.

PMID- 18043011
TI  - The conversion of coroner systems to medical examiner systems in the United
      States: a lull in the action.
AB  - Coroner and medical examiner systems in the United States conduct death
      investigations for most deaths that are sudden and unexplained, or which involve
      external causes such as injury and poisoning. They play a very important role in
      the criminal justice, public health, public safety, and medical communities, and
      they also contribute a substantial portion of autopsy-based mortality data to the
      state and federal mortality statistics systems. Death investigations often
      involve complex medical issues and necessarily require the involvement of
      appropriately trained physicians. Over the years, there has been a trend to
      replace the elected lay coroner systems with systems run by appointed, physician
      medical examiners. Presently, about 31% of counties in the United States are
      served by a medical examiners at the county, district, or state level. Between
      1960 and 1989, there was considerable conversion to medical examiner systems, but
      this trend slowed in the 1990s. Since 2000, only 6 counties in the United States
      have converted to a medical examiner system, no states have converted since 1996,
      and 1 county has reverted to a sheriff-coroner system. Possible reasons for this
      decline are discussed, including legislative, political, geographical, financial,
      population-based, and physician manpower distribution factors. It is important to
      ensure that all death investigation systems have appropriate access to medically
      educated and trained physicians such as forensic pathologists.

PMID- 18043012
TI  - Hate crimes and the forensic pathologist.
AB  - Hate crimes represent crimes committed against an individual or group on the
      basis of their race, ethnicity, national origin, religion, sexual orientation,
      gender, gender identity, or disability. For the forensic pathologist, a death
      related to a hate crime should be considered a high-profile case, one in which
      the pathologist should expect abundant public interest and scrutiny. In this
      article, an overview of hate crimes is presented, stressing the different types
      of hate crimes and the motives of those who commit such crimes. For death
      investigators and forensic pathologists, an awareness of these details will help
      them to recognize and appropriately anticipate issues that may be important in
      deaths related to hate crimes.

PMID- 18043013
TI  - Suicidal gunshot wounds to the head: a retrospective review of 406 cases.
AB  - A retrospective review of 406 suicidal gunshot wounds to the head, investigated
      at the Medico-Legal Laboratory of Pretoria, between 1997 and 2000 was performed.
      Fifty-seven percent of fatal suicidal firearm injury to the head occurred in the
      21- to 40-year age range in both male and female victims. Eighty-two percent of
      all these victims of suicidal firearm fatalities to the head were male. Of the
      406 cases, 63% were white, 31% were black, and 6% were of mixed ethnic and/or
      Asian decent. There was a slight increase in incidence around spring and autumn.
      Handguns were used in the majority of cases with shoulder weapons being used in
      18 of the 406 cases. Ninety-two percent of the suicidal gunshot wounds to the
      head occurred indoors. A positive blood alcohol concentration was seen in 40% of
      cases. Of those examined, 81% were contact gunshot wounds. The trajectory was
      upward in 51% of cases and horizontal in 24% of cases. The right temple was the
      most common entrance gunshot wound site. Findings are in keeping with previously
      published literature.

PMID- 18043015
TI  - The incidence and characteristic features of fatal hemorrhage due to ruptured
      varicose veins: a 10-year autopsy study.
AB  - Death due to hemorrhage from ruptured peripheral varicose veins is an uncommon
      event. A review of the files of Forensic Science SA (FSSA) in Adelaide, South
      Australia, was undertaken over a 10-year period from January 1996 to December
      2005 for such cases. A total of 8 cases were found out of a total of 10,686,
      representing <0.01% of autopsy cases. The male to female ratio was 1:3, with an
      age range of 58-84 years (mean = 78 years). The victims were all located at their
      home addresses, where they had been alone at the time of their deaths. Scene
      investigations revealed considerable blood loss, with pooling around the victims'
      bodies, and also in other parts of the house, particularly the bathroom/toilet
      areas. Four ulcers were of an acute perforative type and 2 were of a chronic
      ulcerative type. In 2 cases, bleeding followed trauma. Toxicologic evaluation was
      performed in only 3 of the cases, revealing blood alcohol levels of 0.06% and
      0.14% in 2 cases, respectively. A further victim had been prescribed
      anticoagulant drugs for an unrelated condition. Additional findings of
      significance were ischemic heart disease in 3 cases and deep venous thrombosis of
      the calf veins on the side of the fatal hemorrhage in another case (with no
      evidence of pulmonary thromboembolism). One victim had acute gastric erosions,
      suggesting that hypothermia following collapse played a role in the terminal
      event. Autopsy evaluation of such cases should include careful layer dissection
      of the area of hemorrhage to confirm the presence of the ruptured varix and to
      enable directed histologic sampling.

PMID- 18043014
TI  - Nursing home deaths which fall under the jurisdiction of the coroner: an 11-year
      retrospective study.
AB  - Twenty percent of deaths in the United States occur in nursing homes, yet less
      than 1% come to autopsy. The current study analyzed causes and manners of death
      in all nursing homes between 1993 and 2003, investigated by the coroner of
      Allegheny County, PA, which has the second highest elderly population in the
      United States. Two hundred eight decedents were identified, aged 19 to 91 years,
      58% women and 42% men, 88% Caucasian and 22% African-American. Fifty-eight
      percent were accidental and 38.5% were natural manners of death, with 2
      homicides, 2 suicides, and 3 undetermined cases. The manner of death was
      significantly different between Caucasians and African-Americans, with 92.6% of
      accidental deaths occurring in Caucasians and 6.6% in African-Americans (P <
      0.1). Most common natural deaths were arteriosclerotic cardiovascular disease,
      nonarteriosclerotic cardiovascular disease, pneumonia, pulmonary thromboembolism,
      chronic obstructive pulmonary disease (COPD), seizure disorder, and atraumatic
      intracranial hemorrhage. Blunt force trauma was the single most commonly
      identified traumatic accidental death. Accidental deaths were more common in
      Caucasians than African-Americans. Homicides and suicides were rare events (<2%).
      Blunt force trauma is a major autopsy finding in accidental nursing home deaths,
      and a root-cause analysis may be helpful in developing policies and procedures to
      decrease the incidence of blunt force trauma.

PMID- 18043016
TI  - Asphyxial games in children and adolescents.
AB  - Asphyxial games, as played by young adolescents, and going by various names, are
      not new phenomena. What seems to be different at present is an increase in
      lethality introduced by the increasing use of ligatures and "playing" the game
      alone. The authors present a properly certified but insufficiently appreciated
      case followed 2 years later by 2 closely spaced but unrelated deaths in young
      adolescent males that made known this practice in New Hampshire youth. Other
      cases presented to the author from other jurisdictions are reviewed in aggregate.
      Presented are characteristics of victims of this practice that may help
      distinguish these deaths from suicidal asphyxia. A relative paucity of literature
      regarding asphyxial games outside the realm of autoerotic asphyxia gives rise to
      certification difficulties given the high prevalence of youth suicide.

PMID- 18043017
TI  - The application of mitochondrial DNA cytochrome oxidase II gene for the
      identification of forensically important blowflies in Western China.
AB  - Blowflies found on human corpses are important for the estimation of the
      postmortem interval and other questions of forensic relevance. Some of these
      species are difficult to differentiate morphologically, and therefore a molecular
      method was elaborated for species identification. Here, we describe a molecular
      method for rapid identification of these insects. Specific insect DNA fragments
      were amplified using the polymerase chain reaction, followed by direct DNA
      sequencing of the amplification products. Analysis of the cytochrome oxidase II
      sequences revealed abundant phylogenetically informative nucleotide substitutions
      that could identify blowfly species to species group. In contrast, because of the
      low level of sequence divergence of sister species, the data could not
      distinguish among taxa from the same species group, ie, the species within the
      Lucilia sericata and Lucilia cuprina groups. The molecular data support the
      existing species group separation of the taxa within the Calliphora. Because of
      the speed and accuracy of current nucleotide sequencing technology and the
      abundant apomorphic substitutions available from mtDNA sequences, this approach
      enables quick identification of species used for estimation of postmortem
      interval.

PMID- 18043018
TI  - Homicide-suicide (dyadic death), homicide, and firearms use in England and Wales.
AB  - Homicide-suicide forms a distinct form of homicide. An analysis of cases in the
      Yorkshire and Humberside region of England between 1991 and 2005 revealed 37
      episodes with 42 victims. Previous studies have shown a high rate of use of
      firearms. Over the last 2 decades firearms legislation has become more
      restrictive. In this study all assailants were male, mean age 46.8 years. The
      commonest method of homicide was strangulation (36%) with 16% killed by firearms.
      This is a reduction compared with a previous study in the same region. All
      killers who shot their victims killed themselves with firearms. There were no
      multiple killings with firearms in this study and no stranger killings. Hanging
      was the commonest method of suicide. During the same period the use of firearms
      as a method of homicide increased in England and Wales with handguns, the most
      common weapon. Nationally, suicide after homicide has remained at a similar rate
      over the half century and is an uncommon phenomenon. Firearms use remains low in
      both homicide and homicide-suicide episodes in England, and further analysis is
      required to determine changes in patterns of killing.

PMID- 18043019
TI  - Inhalant deaths in South Australia: a 20-year retrospective autopsy study.
AB  - A 20-year retrospective study of inhalant deaths in South Australia, autopsied at
      Forensic Science SA, was undertaken from January 1983 to December 2002. Thirty
      nine cases were identified from an autopsy pool of 18,880 cases, with a male to
      female ratio of 12:1. Sixty-four percent of the victims (N = 25) died during
      voluntary inhalation of volatile substances and 28% (N = 11) committed suicide
      utilizing a volatile substance or gas. The remaining 3 cases involved a workplace
      accident (N = 1) and 2 cases of autoerotic death where inhalants were being used
      to augment solitary sexual activity. The mean age of the 28 victims of accidental
      inhalant death of 21 years (range, 13-45 years) was considerably less than that
      of the 11 suicide victims of 31.5 years (range, 17-48 years). No homicides were
      found. Approximately one quarter of the victims were Aboriginal (N = 11), 10 of
      whom had died as a result of gasoline inhalation ("petrol sniffing"). Other
      common substances of abuse were aliphatic hydrocarbons such as butane. The study
      has shown that those most at risk for accidental or suicidal inhalant deaths were
      young males, with 92% of victims overall being male, and with 77% of victims
      being under 31 years of age. Gasoline inhalation remains a significant problem in
      Aboriginal communities in South Australia.

PMID- 18043020
TI  - Guidelines for postmortem protocol for ocular investigation of sudden unexplained
      infant death and suspected physical child abuse.
AB  - Postmortem examination is a cornerstone in identifying the cause of unexplained
      sudden death in children. Even in cases of suspected or known abuse, an autopsy
      may help characterize the nature of the abuse, which is particularly important in
      the forensic autopsy of children in the first 3 to 4 years of life when inflicted
      neurotrauma is most common. Forensic examinations are vital in cases that might
      otherwise be diagnosed as sudden infant death syndrome. The ocular autopsy in
      particular may demonstrate findings that were not appreciated on antemortem
      clinical examination. This protocol for postmortem examination of the eyes and
      orbits was developed to promote more consistent documentation of findings,
      improved clinical and forensic decision making, and more replicable and coherent
      research outcomes.

PMID- 18043021
TI  - Fatal positional asphyxia associated with rollover crashes.
AB  - Motor vehicle rollover crashes result in complex occupant kinematics with the
      potential for severe injury. Five cases of fatal asphyxia in occupants suspended
      from their safety belt upside down after a rollover crash are presented. These
      fatalities accounted for 13.5% of all motor vehicle related asphyxia deaths in
      San Diego County over a 10-year period. This study supports previous research
      noting that incapacitation due to other injuries, alcohol, or obesity may be
      associated with fatal positional asphyxia due to inversion during rollovers.
      Safety belts are proven to prevent serious injury in motor vehicle crashes and
      should always be worn. However, redesign of the buckle could be considered to
      permit easier release by an occupant. We also suggest that pre-existing heart
      disease may contribute to the possibility of a fatal asphyxia outcome. Although
      this is a rare cause of motor vehicle related death, our results suggest that
      these are potentially preventable deaths.

PMID- 18043022
TI  - DNA extraction: an anthropologic aspect of bone remains from sixth- to seventh
      century ad bone remains.
AB  - In the archeological site of the early Christian Episcopal complex of Saint
      Peter, in Canosa di Puglia (Bari, Italy), during the operations of archaeological
      excavations, tombs were discovered. They were dated between the sixth and seventh
      centuries ad with carbon 14 methodology. Five skeletons were found in the 5
      tombs: 28A: male individual, 43 years old. The height was 170 cm; the biomass was
      65.7 kg. The analysis of the bones indicated several noteworthy pathologies, such
      as a number of hypoplasia lines of the enamel, the presence of Schmorl hernias on
      the first 2 lumbar vertebrae, and the outcome of subacromial impingement
      syndrome. 28E was a male individual, with a biologic age of death of between 44
      and 60 years. The height was 177 cm. He had a posttraumatic fracture callus of
      the medial third of the clavicle, with an oblique fracture rima. 29B was a female
      individual, 44-49 years old. The height was 158.8 cm; the biomass was 64.8 kg.
      There was Wells bursitis on the ischial tuberosity on both sides. 29E was a male
      individual, 45-50 years old. The height was 169.47 cm; the biomass was 70.8 kg.
      The third and the fourth vertebrae showed Baastrup syndrome (compression of the
      vertebral spine). There were radiologic signs of deformity on the higher edge of
      the acetabula and results of frequent sprains of the ankles. 31A was a male
      individual, 47-54 years old. The height was 178.65 cm; the biomass was 81 kg. The
      vertebral index showed a heavy overloading in the thoracic lumbar region. There
      were bony formations under the periosteum on both on the higher and medium facets
      of the first metatarsus and on the higher and lateral facets of the fifth
      metatarsus on both sides. As the topography indicates, these small ossifications
      coincided with the contact points between the back of the foot and parts of the
      upper shoe. From the osseous remains, in particular from the teeth (central
      incisors), the DNA was extracted and typed to identify potential family ties
      among all the subjects. The extraction technique used came from the DNA Promega
      technique, partially modified by the authors. Stay times of the sample in the
      extraction buffer were increased and were increased the polymerase chain reaction
      (PCR) cycles.

PMID- 18043023
TI  - Sudden death due to dissecting pulmonary artery aneurysm: a case report and
      review of the literature.
AB  - Pulmonary artery aneurysm and pulmonary artery dissection are rare antemortem
      diagnoses, most often associated with sudden death. These pathologic entities are
      strongly associated with chronic pulmonary hypertension due to structural cardiac
      defects, either congenital or acquired. We report the case of a 49-year-old woman
      who died suddenly due to dissection and rupture of a large pulmonary trunk
      aneurysm, with subsequent cardiac tamponade. Key historical and physical findings
      are described. Additionally, we present a discussion of the incidence, clinical
      presentation, pathogenesis, and pathologic diagnostic features of pulmonary
      artery dissection.

PMID- 18043024
TI  - Fracture of the hyoid bone associated with atlantoaxial subluxation: a case
      report and review of the literature.
AB  - Hyoid bone fractures secondary to blunt trauma other than strangulation are rare.
      Only 27 cases have been reported in the literature. They have few, if any,
      complications, such as dysphagia, hypoxia, cardiorespiratory collapse, laceration
      of the pharynx, mandibular fracture, thyroid cartilage fracture, and facial
      fracture. No report of hyoid bone fracture associated with spinal column injury
      was reported in the English literature. The authors reported a 46-year-old male
      patient who complained of neck pain and odynophagia after a traffic accident.
      After systemic examination and cervical CT scan, the diagnosis of hyoid bone
      fracture at the right great horn and atlantoaxial subluxation was made. The
      patient was observed in ICU for 48 hours. A nasogastric tube was inserted for
      feeding. Fifteen milligrams of dexamethasone was given once a day for 3 days to
      reduce the swelling and pain. We performed a cutaneous traction for the
      subluxation and carefully watched the hyoid bone and the patient's respiration.
      No lethal complications occurred. Two weeks later, the patient was allowed to
      ambulate with cervical collar protection and to resume oral intake. Three months
      later, he was asymptomatic. This case, with hyoid fracture and atlantoaxial
      subluxation, is the only case reported in the literature. The importance of hyoid
      fracture, however, rests not with the rarity of it, but with the lethal potential
      of missing diagnosis. Nonsurgical management may be effective in most of the
      cases.

PMID- 18043025
TI  - A fatal case of hypothermia associated with hemorrhages of the pectoralis minor,
      intercostal, and iliopsoas muscles.
AB  - In a morning in January, a male in his early sixties was found dead in an outdoor
      parking area. The minimum temperature during the night before he was found dead
      was estimated to be 4.0 degrees C. Autopsy revealed the pinkness of hypostasis,
      slight abrasions and bruises on the face and the extremities, collapse of the
      lungs, and slight gastric submucosal hemorrhage. Histologic examination revealed
      compact arrangement of cardiac muscle fibers and cytoplasmic vacuolation in the
      adenohypophysis. Toxicologic examination demonstrated hyperacetonemia (51.2
      microg/mL). Ubiquitin, one of the stress proteins that are induced by several
      stimuli, including severe cold, was detected in several organs. We concluded that
      the cause of his death was lethal hypothermia. In addition, hemorrhages were
      observed in the subfascial and/or intramuscular parts of the pectoralis minor,
      first intercostal, and iliopsoas muscles. Although it has been reported that
      iliopsoas muscle hemorrhage can result from hypothermia, there have been few
      reports concerning hypothermia-associated hemorrhages of the pectoralis minor
      and/or intercostal muscles. We presumed that intense shivering and/or effort
      ventilation during the course of lethal hypothermia might cause these muscle
      hemorrhages.

PMID- 18043026
TI  - Spontaneous ignition in case of celphos poisoning.
AB  - Celphos (aluminum phosphide) poisoning is the most common cause of poisoning in
      India. The mechanism of action, acute and chronic effect on human body, its
      symptoms and signs, and the line of treatment are well documented and research is
      still going on to find a suitable antidote. "Spontaneous ignition" is a rare but
      interesting finding in case of aluminum phosphide poisoning. We present the
      autopsy findings in this case report along with the probable factors that led to
      occurrence of such finding.

PMID- 18043027
TI  - Pitbull mauling deaths in Detroit.
AB  - Between the years 1987 and 2005, there were 6 deaths reported in Wayne County,
      Michigan, associated with pitbull dog attacks. This article discusses the age
      incidence, scene investigation, nature of the injuries, and discussion relative
      to fatal dog attacks, an unusual accidental type of death.

PMID- 18043028
TI  - Fatal intoxication with a selective serotonin reuptake inhibitor, lorazepam, and
      codeine.
AB  - Selective serotonin reuptake inhibitors were introduced in 1987 as an alternative
      treatment option for patients with depression or certain anxiety disorders.
      Unfortunately, this greater use has prompted a corresponding increase in reports
      of more severe side effects and fatalities, with a majority of fatalities
      occurring due to coingestion of selective serotonin reuptake inhibitors with
      other substances or serotonergic drugs. We report a case which exemplifies one
      such fatality related to sertraline, lorazepam, and codeine coingestion. A brief
      discussion of the presumed mechanism by which death occurred will be offered.

PMID- 18043029
TI  - Asphyxial suicide by inhalation of helium inside a plastic bag.
AB  - Asphyxial suicide by placing a plastic bag over the head, especially in
      combination with inhalation of gases, is a rarely described method of committing
      suicide. This article reports a case of suicidal asphyxiation by inhaling the
      inert gas helium inside a plastic bag. A 64-year-old man probably followed the
      instructions described in an article about committing suicide written by a
      medical practitioner from Zurich. This form of suicide is recommended by right-to
      die groups and in the internet as a certain, fast, and painless suicide method.
      Additionally, it leaves only seldom externally visible marks or
      pathomorphological findings on the body. If the plastic bag and other auxiliary
      means are removed by another person, the forensic death investigation of cause
      and manner of death may be very difficult. Therefore, the death scene
      investigation and the inquiry ordered in the environment of the deceased are very
      important.

PMID- 18043030
TI  - A large fragment of a knife under the edge of an incised wound: is it possible?

PMID- 18043031
TI  - The correlation between rates of unemployment and the suicide rate in Mie
      Prefecture, Japan.

PMID- 18043032
TI  - Squamous cell carcinoma of the bladder: a clinicopathologic analysis of 45 cases.
AB  - Squamous cell carcinoma of the bladder comprises less than 5% of all bladder
      cancers in the United States and its long-term prognosis has remained
      controversial. We examined a large series of patients who underwent radical and
      partial cystectomies for squamous cell carcinoma to identify associated
      histopathologic findings and clinical outcomes associated with these tumors.
      Patient age ranged from 46 to 83 years (average 68.5 y) with a male:female ratio
      of 3:2. Forty-three patients were white and 2 patients were African-American. No
      patient had a history of schistosomal infection and only 1 patient had a history
      of condyloma acuminatum. The majority of patients with reported signs and
      symptoms presented with hematuria (n=29/34), with the remainder presenting with
      lower urinary tract symptoms. Tumor size ranged from 0.8 to 6.4 cm (average 3.8
      cm). Invasion was identified into the lamina propria (pT1, n=1/45), muscularis
      propria (pT2, n=14/45), perivesical fat (pT3, n=27/45), and adjacent structures
      (pT4, n=3/45). Concurrent metastases were identified in 11 of 45 patients (24%)
      to pelvic lymph nodes (n=9), perivesical lymph nodes (n=3), obturator lymph nodes
      (n=1), and bowel wall (n=1). Most tumors were moderately (n=29/45) or poorly
      (n=13/45) differentiated, whereas only 3 tumors were well differentiated
      (n=3/45). Keratinization was present in all cases within the invasive component
      and ranged from 5% to 95% of tumor bulk. Necrosis ranged from 0% to 60% and
      inversely correlated with tumor differentiation. Eighteen cases demonstrated a
      prominent giant cell reaction to keratin, and 30 tumors were associated with a
      desmoplastic reaction. Extensive perineural (n=11/45) and angiolymphatic invasion
      (n=7/45) were identified in a subset of tumors. The majority of cases
      demonstrated associated superficial lesions including keratinizing squamous
      metaplasia (n=28/45), nonkeratinizing squamous metaplasia (n=20/45), squamous
      cell carcinoma in situ (n=16/45), squamous metaplasia with dysplasia (n=4/45),
      verrucous squamous hyperplasia (n=3/45), and extensive condyloma acuminatum
      (n=1/45). Seven cases additionally demonstrated separate small foci of focal flat
      urothelial carcinoma in situ. Three cases demonstrated a markedly atypical
      squamous lining of the prostatic ducts at the prostatic urethra. Clinical follow
      up was available on 35 patients (78%) and ranged from 1 to 175 months (average 33
      mo, median 15 mo). Two patients developed recurrent local disease (n=2/35, 6%)
      and 13 patients developed subsequent metastatic disease (n=13/35, 37%). Ten
      patients were dead of disease (29%), with a time to death for most patients of
      less than 2 years (range 2 to 21 mo, average 10.5 mo). Thirty-seven percent of
      patients (n=13/35) were alive without disease. In conclusion, squamous cell
      carcinoma often presents at an advanced stage; however, radical cystectomy with
      lymph node dissection appears to offer a significant benefit in survival in a
      subset of patients.

PMID- 18043033
TI  - Intrahepatic cholangiocarcinoma metastatic to the ovary: a report of 16 cases of
      an underemphasized form of secondary tumor in the ovary that may mimic primary
      neoplasia.
AB  - The potential for adenocarcinoma metastatic to the ovary to mimic primary
      mucinous neoplasms is a well-known issue to surgical pathologists, most of the
      recent literature emphasizing pancreatic and various other origins for the
      ovarian metastases. Although an origin in the gallbladder or extrahepatic bile
      ducts is acknowledged for some cases little information exists on tumors
      originating within the intrahepatic bile ducts. Sixteen cases of this type were
      retrieved from the surgical pathology files of the Chiang Mai University Hospital
      between January 1992 and December 2006. The patients ranged from 38 to 74 years
      (mean 52). Thirteen presented with nonspecific pelvic symptoms similar to primary
      ovarian neoplasms. The hepatic tumors were radiologically detected before the
      ovarian lesion in 2 cases. Hepatic and ovarian masses were simultaneously
      detected by preoperative radiologic studies or at exploratory laparotomy in 10
      cases. In the remaining 4 cases, the hepatic lesions were detected
      postoperatively. There were a total of 26 metastatic ovarian lesions which
      included 22 clinically recognized ovarian masses (range 3 to 20 cm, mean 11.8
      cm). Bilateral involvement was present in 10 cases (62%) and unilateral
      involvement in 6 (38%). The cut surfaces of the 22 grossly enlarged ovaries were
      predominantly solid in 5, solid-cystic in 10, and multicystic in 7.
      Microscopically, surface implants were observed in 80% of tumors, multinodular
      growth in 48%, and infiltrative stromal invasion (including microinvasionlike
      foci as it would be applied if the tumors were primary) in 86%. The neoplastic
      epithelium typically formed glands that ranged from small to large and cystically
      dilated, but small clusters of cells and individual cells were also seen. The
      epithelium ranged from tall, columnar, and mucinous in appearance to cuboidal or
      flattened and nonspecific. The tumors most closely mimicked primary mucinous
      neoplasms although a resemblance to other mullerian neoplasms was also seen. Foci
      often mimicked mucinous borderline tumors of typical type or with intraepithelial
      carcinoma and benign-appearing mucinous epithelium was seen in 62% of tumors.
      Immunohistochemical studies in 15 cases showed a positive reaction for
      cytokeratin 7 in all and for cytokeratin 20 in 5 cases. Intrahepatic
      cholangiocarcinoma should be included in the list of origins of possible ovarian
      metastatic tumors that mimic primary ovarian mucinous neoplasia, particularly in
      parts of the world where cholangiocarcinoma of the liver is relatively common.

PMID- 18043034
TI  - Gastrointestinal tract pathology in patients with common variable
      immunodeficiency (CVID): a clinicopathologic study and review.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is characterized by a host of
      gastrointestinal (GI) lesions that can mimic other conditions. METHODS: We
      reviewed clinical documentation and samples from 132 separate GI biopsy or
      resection sites on 20 CVID patients obtained over a 26-year period, including
      biopsies from the colon (34), esophagus (19), small intestine (38), and stomach
      (35), a partial gastrectomy, small bowel resection, colectomy, 2
      cholecystectomies, and 1 appendectomy. RESULTS: There were 13 males and 7
      females. Nine patients were children (10 y and younger) and 11 were adults. Age
      at diagnosis ranged from 6 months to 62 years (median, 35.5 y), and age at biopsy
      ranged from 10 months to 67 years (median, 38 y). Esophageal samples often showed
      intraepithelial neutrophils, accompanied by candida. Half of patients' esophageal
      biopsies had prominent intraepithelial lymphocytosis, one of which also had
      prominent apoptosis. The stomachs of 67% of patients lacked plasma cells. Most
      showed lymphoid aggregates. An increase in apoptosis was detected in biopsies
      from a third. About 20% had a lymphocytic gastritis pattern. Intraepithelial
      neutrophils were found in a subset, accompanied by various infections
      [cytomegalovirus (CMV), Helicobacter pylori, and Cryptosporidium]. Granulomas
      were found in 1 patient. Gastric adenocarcinoma was identified in one patient.
      There was a paucity of small bowel plasma cells in the majority of patients
      (68%). The small bowel showed prominent lymphoid aggregates in about half (47%).
      An increase in apoptosis was detected in specimens from about 20%. Increased
      intraepithelial lymphocytes (IELs) were found in samples from over half of
      patients (63%), most of whom (83%) also had villous blunting, mimicking celiac
      disease. Intraepithelial neutrophils were found in a subset (32%) and correlated
      with CMV and Cryptosporidium infections. Granulomas were seen in biopsies from 2
      patients (11%). One patient had a collagenous enteritis pattern (accompanied by a
      collagenous colitis pattern). One patient had autoimmune enteritis; biopsies from
      this patient were initially relatively normal but later displayed prominent crypt
      apoptosis and loss of goblet cells. In colon samples, a paucity of plasma cells
      was seen in 10 patients (63%). The colon showed lymphoid aggregates in most
      patients (81%). Apoptosis was prominent in samples from half of the patients
      (50%). Biopsies from 6 patients had a lymphocytic colitis pattern (38%) and 2
      patients had a collagenous colitis pattern. Intraepithelial neutrophils were
      found in samples from most patients (88%). Crypt distortion was seen in 6 of
      these patients (43%), thereby mimicking ulcerative or Crohn colitis. Granulomas
      were found in 3 patients (19%). CMV was detected in 1 patient. The appendix from
      1 patient showed Cryptosporidium and acute serositis with a paucity of plasma
      cells and an increase in apoptosis. The gallbladder from 1 patient showed acute
      cholecystitis, and another patient's gallbladder lacked plasma cells.
      CONCLUSIONS: GI tract CVID displays a wide spectrum of histologic patterns. Its
      features can mimic lymphocytic colitis, collagenous enterocolitis, celiac
      disease, lymphocytic gastritis, granulomatous disease, acute graft-versus-host
      disease, and inflammatory bowel disease. In fact, in our series, we found
      patients with a prior diagnosis of celiac disease (25%) and inflammatory bowel
      disease (35%), including Crohn disease (15%). The diagnosis of CVID may be
      suspected on the basis of the lack of plasma cells in a GI biopsy, but because
      this feature is only present in about two-thirds of patients, the diagnosis
      cannot always be suggested in isolation of other clinical and laboratory
      findings.

PMID- 18043035
TI  - Myoepithelial carcinoma of soft tissue in children: an aggressive neoplasm
      analyzed in a series of 29 cases.
AB  - Primary myoepithelial tumors of soft tissue are uncommon, and criteria for
      malignancy among these neoplasms have only recently been established. Of 51
      myoepithelial carcinomas of soft tissue in the literature, 11 occurred in
      children, 7 of which were included in a previous series of myoepithelial tumors
      from our group. We have collected an additional 22 cases of myoepithelial
      carcinoma of soft tissue in the pediatric population, and we describe the
      detailed clinicopathologic features of all 29 cases herein. There were 15 girls
      and 14 boys; age at diagnosis ranged from newborn to 17 years (median, 9 y).
      Sites included extremities (14 cases), trunk (6 cases), viscera (5 cases: 3
      mediastinal, 1 retroperitoneal, and 1 intracardiac), and head/neck (4 cases).
      Histologically, the tumors were heterogeneous, with epithelioid, clear, spindle
      and/or plasmacytoid cells forming nests, cords or solid sheets in a myxoid or
      hyalinized stroma. Epithelioid cells predominated in the majority of cases (27 of
      29; 93%) and in 10 cases (34%), tumor cells focally had scant cytoplasm with
      round cell morphology. The mitotic rate ranged from <1 to 68 per 10 high power
      fields (median, 8), and tumor necrosis was present in 14 cases. At least 1 broad
      spectrum cytokeratin was positive in all tumors [CAM5.2 in 17 of 18 (94%),
      AE1/AE3 in 15 of 20 (75%), and PAN-K in 14 of 21 (67%)], and EMA was positive in
      19 of 29 cases (66%). Either S100 or GFAP was positive in all but 4 cases [S100
      in 21 of 29 (72%) and GFAP in 15 of 28 (54%)]. Clinical follow-up in 23 cases
      revealed that 9 patients had local recurrences (53% of the 17 patients who
      underwent complete excision with negative margins); 12 (52%) developed
      metastases; and 10 (43%) have died of disease so far, at a median interval of 9
      months after diagnosis. Despite the relative rarity of carcinomas in the
      pediatric population, myoepithelial carcinoma seems to be disproportionately
      common among children and often has an aggressive clinical course.

PMID- 18043036
TI  - Improved methods of detection of lymphovascular invasion demonstrate that it is
      the predominant method of vascular invasion in breast cancer and has important
      clinical consequences.
AB  - The presence of vascular invasion (VI), encompassing both lymphovascular invasion
      (LVI) and blood vascular invasion (BVI), in breast cancer has been found to be a
      poor prognostic factor. It is not clear, however, which type of VI plays the
      major role in metastasis. The aims of this study were to use an endothelial
      subtype specific immunohistochemical approach to distinguish between LVI and BVI
      by comparing the differential expression of blood vascular (CD34 and CD31) and
      lymphatic markers (podoplanin/D2-40) to determine their prognostic role in a well
      characterized group of breast cancer patients with known long-term follow-up.
      Sections from 177 consecutive paraffin-embedded archival specimens of primary
      invasive breast cancer were stained for expression of podoplanin, D2-40, CD31,
      and CD34. BVI and LVI were identified and results were correlated with
      clinicopathologic criteria and patient survival. VI was detected in 56/177
      specimens (31.6%); 54 (96.4%) were LVI and 2 (3.5%) were BVI. The presence of LVI
      was significantly associated with the presence of lymph node metastasis, larger
      tumor size, development of distant metastasis, regional recurrence and worse
      disease-free interval and overall survival. In multivariate analysis, LVI
      retained significance association with decreased disease-free interval and
      overall survival. In conclusion, VI in breast cancer is predominantly of lymph
      vessels and is a powerful independent prognostic factor, which is associated with
      risk of recurrence and death from the disease. The use of immunohistochemical
      staining with a lymphendothelial specific marker such as podoplanin/D2-40
      increases the accuracy of identification of patients with tumor associated LVI.

PMID- 18043037
TI  - Human papillomavirus (HPV) profiles of vulvar lesions: possible implications for
      the classification of vulvar squamous cell carcinoma precursors and for the
      efficacy of prophylactic HPV vaccination.
AB  - The term vulvar intraepithelial neoplasia (VIN) introduced in 1986 incorporates 3
      grades of usual VIN (u-VIN I-III) and the differentiated VIN (d-VIN). Although u
      VIN is etiologically associated with the human papillomavirus (HPV) infection, d
      VIN represents an alternative HPV negative pathway of vulvar carcinogenesis. In
      2004, the u-VIN I category was abandoned and u-VIN II and III were merged.
      Further, an alternative Bethesda-like terminology scheme presenting the term
      vulvar intraepithelial lesion was proposed recently. To analyze the impact of HPV
      profiles of vulvar precancerous lesions for their classification and to assess
      the presumable efficacy of the prophylactic HPV vaccination, 269 vulvar excisions
      representing lichen sclerosus, lichen simplex chronicus, condylomata acuminata, d
      VIN, all grades of u-VIN and squamous cell carcinomas were subjected to the HPV
      typing by use of GP5+/6+ polymerase chain reaction and reverse line blot
      hybridization. The results showed different HPV profiles, and also differing
      frequency of multiple-type HPV infection and the age structure in patients with u
      VIN II and III. The biologic heterogeneity within the u-VIN II category was also
      demonstrated. u-VIN I was distinguished as a rare disorder associated with high
      risk HPV infection. We conclude that the original VIN terminology proposed in
      1986 seems to be appropriate for the classification of vulvar squamous dysplastic
      lesions. The spectrum of HPV types found in vulvar squamous cell carcinomas
      indicates that the efficacy of HPV vaccination in preventing vulvar cancer might
      be diminished in the studied population, because the recently developed
      prophylactic vaccines are targeted against a limited number of HPV types.

PMID- 18043038
TI  - Pulmonary chondroma: a tumor associated with Carney triad and different from
      pulmonary hamartoma.
AB  - The Carney triad is the clinical association of gastric stromal sarcomas,
      pulmonary cartilaginous tumors, and extra-adrenal paragangliomas. The pulmonary
      tumors are its second commonest component and have been misinterpreted clinically
      and pathologically as metastases from the gastric tumors and pulmonary
      cartilaginous hamartomas, respectively. They have not been previously described
      in detail in the pathology literature or compared with pulmonary cartilaginous
      hamartomas. Forty-two patients with pulmonary cartilaginous tumors as a component
      of Carney triad were identified. Clinical, radiographic, and pathologic findings
      in the cases were tabulated. Hematoxylin and eosin-stained sections of the
      neoplasms were evaluated for a series of histologic features. A subgroup of 41
      tumors from the latter was compared with those in a group of pulmonary
      cartilaginous hamartomas. Patients with Carney triad group were predominantly
      young women. Their pulmonary neoplasm(s) were usually asymptomatic, often
      multiple, well circumscribed, medium-sized (mean diameter=2.8 cm), and composed
      almost exclusively of cartilage and bone surrounded by a fibrous pseudocapsule.
      The cartilage was usually myxoid, less frequently hyaline, and commonly
      calcified, ossified, or both. They showed no fat, smooth muscle or entrapped
      respiratory epithelium, tissues that were common in pulmonary hamartoma
      (P<0.0001). None of the tumors metastasized or was fatal. The pulmonary neoplasms
      in the Carney triad are well-differentiated benign cartilaginous tumors that are
      best designated as chondromas. They differ pathologically from pulmonary
      cartilaginous hamartomas on the basis of the presence of a thin fibrous
      pseudocapsule, frequent bone metaplasia, and calcification, and also the absence
      of entrapped epithelium and fat.

PMID- 18043039
TI  - Longitudinal evaluation of interobserver and intraobserver agreement of cervical
      intraepithelial neoplasia diagnosis among an experienced panel of gynecologic
      pathologists.
AB  - Histologic diagnoses of cervical intraepithelial neoplasia grades 2 and 3 (CIN
      2/3) are the key end points in clinical trials that evaluate the efficacy of a
      prophylactic quadrivalent human papillomavirus vaccine against cervical cancer.
      Adjudication of end points uses a panel of 4 pathologists. Quality control slides
      (n=185) from a nonclinical trial study with preestablished gold standard CIN
      diagnoses were used to characterize the panel's agreement on CIN diagnoses and
      monitor performance longitudinally. At 3-month intervals over 2 years, 1 of 6
      different batches of quality control slides (n=30-31) was included with clinical
      trial slides for independent review by each of the 4 panelists. Unweighted kappas
      (kappa) were estimated within each panelist pair by dichotomizing the diagnoses
      as CIN+ versus non-CIN+ (including normal, unsatisfactory, and atypical immature
      metaplasia) or CIN 2/3+ versus non-CIN 2/3+ (including normal, unsatisfactory,
      atypical immature metaplasia, and CIN 1). Quadratic weighted kappa was calculated
      within each panelist pair using 4 diagnostic categories: normal, CIN 1, CIN 2,
      and CIN 3 or worse. Substantial interobserver agreement was observed (weighted
      kappa=0.765 to 0.865). Agreement with weighted kappa=0.779 to 0.887 was observed
      between the individual panelists and the gold standard, which is almost perfect
      agreement by Landis-defined categories. Intraobserver agreement was very high
      (weighted kappa=0.756 to 0.883). Some fluctuation in intraobserver and
      interobserver agreement was observed over the study period but there was no
      decreasing time trend. These data indicate that the interpretation of histologic
      end points used in the quadrivalent vaccine clinical trial program is highly
      valid and reliable.

PMID- 18043040
TI  - Urothelial carcinoma with an inverted growth pattern can be distinguished from
      inverted papilloma by fluorescence in situ hybridization, immunohistochemistry,
      and morphologic analysis.
AB  - Inverted papilloma of the urinary bladder and urothelial carcinoma with an
      inverted (endophytic) growth pattern may be difficult to distinguish
      histologically, especially in small biopsies. The distinction is important as
      these lesions have very different biologic behaviors and are treated differently.
      We examined histologic features and undertook immunohistochemical staining and
      UroVysion fluorescence in situ hybridization (FISH) to determine whether these
      methods could aid in making this distinction. We examined histologic sections
      from 15 inverted papillomas and 29 urothelial carcinomas with an inverted growth
      pattern. Each tumor was stained with antibodies to Ki-67, p53, and cytokeratin
      20. In addition, each tumor was examined with UroVysion FISH for gains of
      chromosomes 3, 7, and 17 and for loss of chromosome 9p21 signals. None of the
      inverted papillomas stained positively for Ki-67 or for cytokeratin 20. Only 1 of
      15 inverted papillomas stained positively for p53. By contrast, 66%, 59%, and 59%
      of urothelial carcinomas with an inverted growth pattern stained positively for
      Ki-67, p53, and cytokeratin 20, respectively. Only 3 of the urothelial carcinomas
      stained negatively for all 3 immunohistochemical markers. UroVysion FISH produced
      normal results for all cases of inverted papilloma. By contrast, 21 of 29 cases
      (72%) of urothelial carcinoma with an inverted growth pattern demonstrated
      chromosomal abnormalities typical of urothelial cancer and were considered
      positive by UroVysion FISH criteria. Morphologic features, as well as
      immunohistochemical stains (including stains for Ki-67, p53, and cytokeratin 20)
      and/or UroVysion FISH can help to distinguish inverted papilloma from urothelial
      carcinoma with an inverted growth pattern.

PMID- 18043041
TI  - Primary mediastinal liposarcoma: clinicopathologic analysis of 24 cases.
AB  - Liposarcomas are rare in the mediastinum. Here, we report the clinicopathologic
      features of 24 cases of mediastinal liposarcoma. Patients included 13 males and
      11 females, with an age range of 3 to 72 years (median 58). Nine tumors were
      located in the anterior mediastinum, 7 in the posterior mediastinum, 1 in the
      superior mediastinum, and the precise location was not specified in 7 cases. Of
      the anterior mediastinal tumors, 3 appeared to arise from the thymus. Tumors were
      well-circumscribed, multinodular masses and ranged in size from 2.2 to 61 cm in
      greatest dimension (median 16 cm). Histologic examination revealed that most of
      the cases were well-differentiated liposarcomas (10), followed by
      dedifferentiated liposarcomas (8), pleomorphic liposarcomas (4), and myxoid
      liposarcomas (2). Of the pleomorphic liposarcomas, 2 had areas that resembled
      myxofibrosarcoma with atypical hyperchromatic spindle cells in a myxoid stroma,
      but the focal presence of lipoblasts confirmed the diagnoses. Clinical follow-up
      was obtained in 15 cases (range 1 to 59 mo; median 26). Complete surgical
      excision was attempted in 13 patients; however, local recurrence was common (5
      cases), including 1 patient whose tumor recurred twice. Eleven patients were
      alive with no evidence of disease at last follow-up (5 well-differentiated, 5
      dedifferentiated, and 1 myxoid liposarcoma). Two patients developed distant
      metastases (dedifferentiated and pleomorphic liposarcoma). One patient was alive
      with disease (pleomorphic liposarcoma), and 2 died of disease (pleomorphic and
      dedifferentiated liposarcoma). Overall, mediastinal liposarcomas appear to be
      similar, in clinicopathologic terms, to liposarcomas arising in the
      retroperitoneum.

PMID- 18043042
TI  - Nuclear expression of hypoxia-inducible factor-1alpha in clear cell renal cell
      carcinoma is involved in tumor progression.
AB  - OBJECTIVES: The most frequent genomic abnormality in clear cell renal cell
      carcinoma (cc-RCC) is inactivation of Von Hippel-Lindau gene (VHL). pVHL19 is a
      ligase promoting proteosomal degradation of hypoxia-inducible factor-1alpha (HIF
      1alpha); pVHL30 is associated with microtubules. VHL exert its oncogenetic action
      both directly and through HIF-1alpha activation. TNM classification is unable to
      define a correct prognostic evaluation of intracapsular cc-RCC. The nucleo
      cytoplasmic trafficking in VHL/HIF-1alpha pathway could be relevant in
      understanding the molecular pathogenesis of renal carcinogenesis. This study
      analyzes VHL/HIF-1alpha proteins in a large series of intracapsular cc-RCCs,
      correlating their expression and cellular localization with prognosis. MATERIALS
      AND METHODS: Two anti-pVHL (clones Ig32 and Ig33) and 1 anti-HIF-1alpha were used
      on tissue microarrays from 136 intracapsular cc-RCCs (mean follow-up: 74 mo).
      Clone 32 recognizes both pVHLs, whereas clone 33 only pVHL30. Results were
      matched with clinicopathologic variables and tumor-specific survival (TSS).
      RESULTS: A strong cytoplasmic positivity was found for all antibodies in the
      largest part of cases, associated to a strong nuclear localization in the case of
      HIF-1alpha. All pVHL-negative cases were associated with high HIF-1alpha
      expression. pVHL negativity and HIF-1alpha nuclear positivity significantly
      correlated with shorter TSS. In multivariate analysis both pVHL negativity and
      HIF-1alpha nuclear expression were independent predictors of TSS. CONCLUSIONS:
      The localization of the proteins well matches with their role and with the
      supposed tumor molecular pathways. The correlation with prognosis of VHL/HIF
      1alpha alterations confirms the relevance of their molecular pathway and of the
      cellular trafficking of their products in the pathogenesis of renal cancer.

PMID- 18043043
TI  - Poorly differentiated colorectal carcinoma with invasion restricted to lamina
      propria (intramucosal carcinoma): a follow-up study of 15 cases.
AB  - Invasive colorectal carcinomas (CRCs) with invasion confined to the lamina
      propria (LP) [intramucosal carcinoma (IMC)] lack access to lymphatics and
      therefore have no potential for metastases and local intervention (usually
      polypectomy) should be adequate treatment. For this reason, they are classified
      as "Tis" in the TNM system. It is believed that carcinomas invading the submucosa
      with unfavorable histology (tumors at/near the margin, and/or vascular invasion,
      and/or poor differentiation) require additional intervention after polypectomy,
      whereas those with favorable histology can be safely treated endoscopically.
      However, there are few data on poorly differentiated (PD) carcinomas showing
      invasion confined to the LP. Polypectomy is theoretically curative but in
      practice this has not been well demonstrated. Thus, the clinicopathologic
      features of 15 cases of PD CRCs with invasion limited to the LP on initial
      biopsies were studied to determine the best course of management for this rare
      subset of carcinomas. A computer search and histologic review of cases seen at
      Johns Hopkins Hospital was performed. Fifteen cases of PD CRC with invasion
      limited to the LP were identified. The clinicopathologic features of these tumors
      were reviewed. All 15 cases showed PD IMC with single cells infiltrating only the
      LP. Patients were 38 to 79 years (median, 62) of age with a male predominance
      (M:F=4:1). Three cases had signet ring cell differentiation, 1 had focal small
      cell features, and another had focal squamous differentiation. Fourteen of the
      cases were associated with background adenomas or adenomalike lesions including:
      7 involving tubulovillous or villous adenomas, 6 involving tubular adenomas, 1
      involving dysplasia associated with chronic inflammatory bowel disease. Nine of
      the lesions had surrounding high-grade dysplasia. One case showed no background
      dysplasia or adenoma. One patient was lost to follow-up and the remaining 14 were
      followed for 1 to 96 months (mean, 21.3 mo; median, 13 mo). Seven patients had no
      residual disease on follow-up colonoscopy, and no resection was performed. The
      remaining 7 patients were treated with partial colectomy (6) or low anterior
      resection (1), and of these, 5 had no infiltrating carcinoma and negative lymph
      nodes. One patient had a separate large colorectal (T3) carcinoma with 8/10
      positive regional lymph nodes; the IMC seen on biopsy was presumably a metastasis
      as it was unassociated with an in situ component. Finally, the resected rectum
      from which an IMC had been previously detected had no residual invasive
      carcinoma, but the anal skin was involved by Paget disease. Thus, of the 15 cases
      of PD CRCs limited to the LP, 1 was a metastasis from a separate CRC and another
      had associated Paget disease of the anal skin. As such, even in the setting of PD
      carcinomas, no metastatic disease was seen arising from any of the cases that
      were confirmed as early primary lesions. These preliminary findings suggest that
      patients with isolated intramucosal PD CRCs may be managed endoscopically.

PMID- 18043044
TI  - Indolent CD8-positive lymphoid proliferation of the ear: a distinct primary
      cutaneous T-cell lymphoma?
AB  - The authors report 4 cases of cutaneous lymphoproliferation unusual by their
      histology and their clinical presentation. Each presented with a history of a
      slow growing nodule on the ear. Despite the indolent clinical evolution, the
      histology suggested a high-grade lymphoma. All lesions consisted of a dense,
      diffuse proliferation of monomorphous medium-sized T cells throughout the dermis
      and subcutis. There was no epidermotropism and a grenz zone was clearly present
      in each case. The tumor cells displayed irregular blastlike nuclei, with small
      nucleoli and clear chromatin and had a CD3+, CD8+, CD4+, TIA1+, granzyme B(
      )immunophenotype with a loss of other T-cell antigens. The 3 cases with available
      material for polymerase chain reaction studies displayed a monoclonal T-cell
      rearrangement of the T-cell receptor-gamma chain. These cases do not correspond
      to a recognized cutaneous T-cell lymphoma as described in the recent WHO/EORTC
      classification. The apparent striking propensity for the ear suggests that they
      might represent a specific entity. Further cases are needed to confirm this
      hypothesis. It is important for such indolent lesions to be known to avoid over
      treatment.

PMID- 18043045
TI  - Misoprostol associated refractile material in fetal and placental tissues after
      medical termination of pregnancy.
AB  - Misoprostol is a synthetic prostaglandin analog administered vaginally to induce
      labor for intrauterine death or termination of pregnancy for congenital
      abnormalities. We encountered a case of misoprostol induction of labor at 14
      weeks of gestation for fetal acrania associated with amniotic bands. Histology
      demonstrated abundant deposits of refractile material appearing to be of
      vegetable fiber origin on the maternal surface of the fetal membranes.
      Misoprostol tablet scrapings had a similar microscopic appearance. Ten additional
      placentas from cases of misoprostol induction of labor between 16 and 18 weeks of
      gestation were examined and half were found to contain such deposits. No deposits
      were seen in cases between 15 and 18 weeks of gestation where misoprostol was not
      used. We attribute the refractile material to a nonmedicinal ingredient,
      microcrystalline cellulose, in the misoprostol tablet preparation. This study
      demonstrates that vaginal administration of misoprostol tablets can be detected
      microscopically in at least half of cases and may have a florid appearance
      simulating a potential causative factor of fetal malformation. Despite the large
      amounts of microcrystalline cellulose and its apparent embedding in placental
      tissue, the misoprostol in our index case was unlikely to have caused the
      amniotic bands and the resulting cranial abnormality.

PMID- 18043046
TI  - Porokeratoma.
AB  - Cornoid lamellation is a specific disorder of epidermal maturation manifested by
      a vertical "column" of parakeratosis and is the hallmark of porokeratosis. The
      cornoid lamella is characterized by a ridgelike parakeratosis. We present 11
      patients with solitary lesions of a distinct pattern of cornoid lamellation. The
      mean age at presentation clinically was 57 years; there were 9 men and 2 women.
      The duration of the lesions ranged from 3 months to 5 years (mean of 23 mo). All
      lesions were solitary, distributed mainly on the distal upper and lower limbs,
      and were clinically described as hyperkeratotic plaques or nodules; some were
      verrucous. Histologic examination showed a well-defined lesion characterized by
      acanthosis and verrucous hyperplasia with prominent multiple and confluent
      cornoid lamellae. No additional lesions were identified in any patient, with a
      mean follow-up duration of 34 months. No personal or family history of
      porokeratosis was elicited and no immunosuppressive conditions were noted. These
      lesions with multiple and confluent cornoid lamellae represent benign acanthomas
      with features of porokeratosis. As a solitary tumorlike lesion, it is akin to
      warty dyskeratoma and epidermolytic acanthoma, thus we have coined the term
      porokeratoma.

PMID- 18043047
TI  - Subungual melanoma: a study of 124 cases highlighting features of early lesions,
      potential pitfalls in diagnosis, and guidelines for histologic reporting.
AB  - Subungual melanoma (SUM) is an uncommon variant of melanoma that is often
      difficult to diagnose, both clinically and pathologically. In an attempt to
      provide pathologic clues to diagnosis, especially in early lesions or small
      biopsies, and to provide practical advice to pathologists in reporting, the
      clinicopathologic features of 124 cases of SUM were reviewed, the largest series
      reported to date. The features of 28 cases of subungual melanoma in situ (MIS),
      comprising 4 cases of MIS and 24 cases where areas of MIS were present adjacent
      to dermal-invasive SUMs, were compared with those of a similar number of acral
      nevi to identify useful distinguishing features. The median age of the patients
      was 59 years and the most common site was the great toe (24%). Nine percent of
      cases were AJCC stage 0, 14% were stage I, 41% were stage II, 32% were stage III,
      and 4% were stage IV at initial diagnosis. The commonest histogenetic subtype was
      acral lentiginous (66%), followed by nodular (25%) and desmoplastic (7%). The
      majority of tumors were locally advanced at presentation with 79% being Clark
      level IV or V. The median Breslow thickness was 3.2 mm. The median mitotic rate
      was 3 per mm and 33% of cases demonstrated primary tumor ulceration. Seven of 29
      patients (24%) who underwent a sentinel lymph node biopsy had nodal disease.
      Multivariate Cox-regression analysis showed higher disease stage to be the only
      significant predictor of shortened survival. In comparison to acral nevi, MIS
      more frequently showed lack of circumscription, a prominent lentiginous growth
      pattern, predominance of single cells over nests, moderate-to-severe cytologic
      atypia, a dense and haphazard pagetoid intraepidermal spread of melanocytes, and
      the presence of junctional/subjunctional lymphocytes ("tumor infiltrating
      lymphocytes"). Tumor infiltrating lymphocytes have not been highlighted
      previously as a feature of subungual MIS and represent a useful diagnostic clue.
      Guidelines for the reporting of SUMs are also presented. Knowledge and
      recognition of the pathologic features of SUMs and the important features that
      distinguish them from nevi should reduce the frequency of misdiagnosis.

PMID- 18043048
TI  - Growing teratoma syndrome of the ovary: review of literature and first report of
      a carcinoid tumor arising in a growing teratoma of the ovary.
AB  - We report the first case of a secondary tumor arising from a peritoneal nodule of
      mature teratoma in a patient with growing teratoma syndrome (GTS) of the ovary.
      The patient originally presented 19 years ago with an immature teratoma of the
      ovary and positive retroperitoneal lymph nodes. After surgery and chemotherapy,
      mature teratomas recurred as abdominal and pelvic masses after 1, 6, and 19
      years. Upon the last recurrence, a trabecular carcinoid tumor developed in a
      mature teratoma associated with the liver. This case illustrates the importance
      of long-term follow-up for patients with GTS of the ovary, where the recurrent
      masses can appear many years after the primary tumor, compress the abdominal and
      pelvic structures and give rise to secondary neoplasms. In addition, we present a
      literature review of GTS of the ovary and some novel observations about this
      entity. On the basis of our review of ovarian GTS cases in the literature, we
      have found that ovarian GTS nodules tend to appear for the first time within 2
      years of the initial primary. They remain confined almost exclusively to the
      pelvis, abdomen, and the retroperitoneum and do not venture to distant systemic
      sites. This new information may help identify and screen women with germ cell
      tumors of the ovary at risk for GTS.

PMID- 18043049
TI  - Early undifferentiated pancreatic carcinoma with osteoclastlike giant cells:
      direct evidence for ductal evolution.
AB  - Undifferentiated (anaplastic) carcinomas of the pancreas are rare. To a variable
      degree, they may contain osteoclastlike giant cells and are then sometimes
      referred to as osteoclastlike giant cell tumors. The histogenesis of these tumors
      has been discussed with great controversy. Thus, as a result from numerous
      histomorphologic, immunohistochemical, ultrastructural, and molecular
      examinations, frequently performed as single case studies, it has been concluded
      that undifferentiated carcinomas and osteoclastlike giant cell tumors of the
      pancreas originate from epithelial cells, mesenchymal cells, undifferentiated
      precursor cells, or stem cells. However, to date, early stage tumors have not
      been described, most likely because of the fact that at the time of diagnosis the
      tumors have commonly reached advanced stages with large tumor size. In this
      report, we present the case of an undifferentiated pancreatic carcinoma with
      osteoclastlike giant cells, which was incidentally detected at a very early stage
      in a pancreatitis specimen. Our histomorphologic and immunohistochemical findings
      not only provide evidence for a ductal origin, but for the first time document
      initial steps in the evolution of these tumors. Therefore, we suggest that the
      tumor should be considered as an anaplastic variant of pancreatic ductal
      adenocarcinoma.

PMID- 18043051
TI  - Developing and exercising the language of airway management.

PMID- 18043052
TI  - Acute renal failure in a general surgical population: risk profiles, mortality,
      and opportunities for improvement.

PMID- 18043053
TI  - P6 stimulation: a new approach to an ancient technique.

PMID- 18043054
TI  - Forward-deployed anesthesiologists and pain treatment in combat support
      hospitals: making decisions about deployment of anesthesiologists in support of
      the global war on terrorism.

PMID- 18043055
TI  - Dynamic interaction of craniofacial structures during head positioning and direct
      laryngoscopy in anesthetized patients with and without difficult laryngoscopy.
AB  - BACKGROUND: We lack fundamental knowledge of the mechanisms of difficult
      laryngoscopy despite its clinical significance. The aim of this study was to
      examine how head positioning and direct laryngoscopy alter arrangements of
      craniofacial structures. METHODS: Digital photographs of the lateral view of the
      head and neck were taken at each step of head positioning and direct laryngoscopy
      in age- and body mass index-matched patients with (n = 13) and without (n = 13)
      difficult laryngoscopy during general anesthesia with muscle paralysis. The
      images were used for measurements of various craniofacial dimensions. RESULTS:
      Both simple neck extension and the sniffing position produced a caudal shift of
      the mandible and a downward shift of the larynx, resulting in an increase of the
      submandibular space. Direct laryngoscopy during the sniffing position displaced
      the mandible and tongue base upward and caudally, and the larynx downward and
      caudally, increasing the submandibular space and facilitating vertical
      arrangement of the mandible, tongue base, and larynx to the facial line. These
      structural arrangements in response to direct laryngoscopy were not observed in
      patients with difficult laryngoscopy, whereas head positioning produced similar
      structural arrangements in patients with and without difficult laryngoscopy.
      CONCLUSION: Increase in the submandibular space and a vertical arrangement of the
      mandible, tongue base, and larynx to the facial line seem to be important
      mechanisms for improving the laryngeal view during head positioning and direct
      laryngoscopy. Failure of these structural arrangements in response to direct
      laryngoscopy may result in difficult laryngoscopy.

PMID- 18043056
TI  - Craniocervical motion during direct laryngoscopy and orotracheal intubation with
      the Macintosh and Miller blades: an in vivo cinefluoroscopic study.
AB  - BACKGROUND: Previous studies have characterized segmental craniocervical motion
      that occurs during direct laryngoscopy and intubation with a Macintosh
      laryngoscope blade. Comparable studies with the Miller blade have not been
      performed. The aim of this study was to compare maximal segmental craniocervical
      motion occurring during direct laryngoscopy and orotracheal intubation with
      Macintosh and Miller blades. METHODS: Eleven anesthetized and pharmacologically
      paralyzed patients underwent two sequential orotracheal intubations, one with a
      Macintosh blade and another with a Miller in random order. During each
      intubation, segmental craniocervical motion from the occiput to the fifth
      cervical vertebra (C5) was recorded using continuous lateral cinefluoroscopy.
      Single-frame images corresponding to the point of maximal cervical motion for
      both blade types were compared with a preintubation image. Using image analysis
      software, angular change in the sagittal plane at each of five intervertebral
      segments was compared between the Macintosh and Miller blades. RESULTS: Extension
      at occiput-C1 was greater with the Macintosh blade compared with the Miller (12.1
      degrees +/- 4.9 degrees vs. 9.5 degrees +/- 3.8 degrees, respectively; mean
      difference = 2.7 degrees +/- 3.0 degrees; P = 0.012). Total craniocervical
      extension (occiput-C5) was also greater with the Macintosh blade compared with
      the Miller (28.1 degrees +/- 9.5 degrees vs. 23.2 degrees +/- 8.4 degrees,
      respectively; mean difference = 4.8 degrees +/- 4.4 degrees; P = 0.008).
      CONCLUSIONS: Compared with the Macintosh, the Miller blade was associated with a
      statistically significant, but quantitatively small, decrease in cervical
      extension. This difference is likely too small to be important in routine
      practice.

PMID- 18043057
TI  - Predictors of postoperative acute renal failure after noncardiac surgery in
      patients with previously normal renal function.
AB  - BACKGROUND: The authors investigated the incidence and risk factors for
      postoperative acute renal failure after major noncardiac surgery among patients
      with previously normal renal function. METHODS: Adult patients undergoing major
      noncardiac surgery with a preoperative calculated creatinine clearance of 80
      ml/min or greater were included in a prospective, observational study at a single
      tertiary care university hospital. Patients were followed for the development of
      acute renal failure (defined as a calculated creatinine clearance of 50 ml/min or
      less) within the first 7 postoperative days. Patient preoperative characteristics
      and intraoperative anesthetic management were evaluated for associations with
      acute renal failure. Thirty-day, 60-day, and 1-yr all-cause mortality was also
      evaluated. RESULTS: A total of 65,043 cases between 2003 and 2006 were reviewed.
      Of these, 15,102 patients met the inclusion criteria; 121 patients developed
      acute renal failure (0.8%), and 14 required renal replacement therapy (0.1%).
      Seven independent preoperative predictors were identified (P < 0.05): age,
      emergent surgery, liver disease, body mass index, high-risk surgery, peripheral
      vascular occlusive disease, and chronic obstructive pulmonary disease
      necessitating chronic bronchodilator therapy. Several intraoperative management
      variables were independent predictors of acute renal failure: total vasopressor
      dose administered, use of a vasopressor infusion, and diuretic administration.
      Acute renal failure was associated with increased 30-day, 60-day, and 1-yr all
      cause mortality. CONCLUSIONS: Several preoperative predictors previously reported
      to be associated with acute renal failure after cardiac surgery were also found
      to be associated with acute renal failure after noncardiac surgery. The use of
      vasopressor and diuretics is also associated with acute renal failure.

PMID- 18043058
TI  - Monitoring of neuromuscular blockade at the P6 acupuncture point reduces the
      incidence of postoperative nausea and vomiting.
AB  - BACKGROUND: Electrical stimulation of the P6 acupuncture point reduces the
      incidence of postoperative nausea and vomiting (PONV). Neuromuscular blockade
      during general anesthesia can be monitored with electrical peripheral nerve
      stimulation at the wrist. The authors tested the effect of neuromuscular
      monitoring over the P6 acupuncture point on the reduction of PONV. METHODS: In
      this prospective, double-blinded, randomized control trial, the authors
      investigated, with institutional review board approval and informed consent, 220
      women undergoing elective laparoscopic surgery anesthetized with fentanyl,
      sevoflurane, and rocuronium. During anesthesia, neuromuscular blockade was
      monitored by a conventional nerve stimulator at a frequency of 1 Hz over the
      ulnar nerve (n = 110, control group) or over the median nerve (n = 110, P6 group)
      stimulating at the P6 acupuncture point at the same time. The authors evaluated
      the incidence of nausea and vomiting during the first 24 h. RESULTS: No
      differences in demographic and morphometric data were found between both groups.
      The 24-h incidence of PONV was 45% in the P6 acupuncture group versus 61% in the
      control group (P = 0.022). Nausea decreased from 56% in the control group to 40%
      in the P6 group (P = 0.022), but emesis decreased only from 28% to 23% (P =
      0.439). Nausea decreased substantially during the first 6 h of the observation
      period (P = 0.009). Fewer subjects in the acupuncture group required ondansetron
      as rescue therapy (27% vs. 39%; P = 0.086). CONCLUSION: Intraoperative P6
      acupuncture point stimulation with a conventional nerve stimulator during surgery
      significantly reduced the incidence of PONV over 24 h. The efficacy of P6
      stimulation is similar to that of commonly used antiemetic drugs in the
      prevention of PONV.

PMID- 18043059
TI  - A facilitated survey instrument captures significantly more anesthesia events
      than does traditional voluntary event reporting.
AB  - BACKGROUND: This study sought to evaluate the effectiveness of an active survey
      method for detecting anesthesia nonroutine events (NREs). An NRE is any aspect of
      clinical care perceived by clinicians or observers as a deviation from optimal
      care based on the context of the clinical situation. METHODS: A Comprehensive
      Open-ended Nonroutine Event Survey (CONES) was developed to elicit NREs. CONES,
      which consisted of multiple brief open-ended questions, was administered to
      anesthesia providers in the postanesthesia care unit. CONES data were compared
      with those from the same hospital's anesthesia quality assurance (QA) process,
      which relied on self-reporting of predefined adverse events. RESULTS: CONES
      interviews were conducted after 183 cases of varying patient, anesthesia, and
      surgical complexity. Fifty-five cases had at least one NRE (30.4% incidence).
      During the same 30-month period, the QA process captured 159 cases with 96.8%
      containing at least one NRE among the 8,303 anesthetic procedures conducted (1.9%
      overall incidence). The CONES data were more representative of the overall
      surgical population. There were significant differences in NRE incidence (P <
      0.001), patient impact (74.5% vs. 96.2%; P < 0.001), and injury (23.6% vs. 60.3%)
      between CONES and QA data. Outcomes were more severe in the QA group (P < 0.001).
      Extrapolation of the CONES data suggested a significantly higher overall
      incidence of anesthesia-related patient injury (7.7% vs. only 1.0% with the QA
      method). CONCLUSIONS: An active surveillance tool using the NRE construct
      identified a large number of clinical cases with potential patient safety
      concerns. This approach may be a useful complement to more traditional QA methods
      of self-reporting.

PMID- 18043060
TI  - Treatment of iron deficiency anemia in orthopedic surgery with intravenous iron:
      efficacy and limits: a prospective study.
AB  - BACKGROUND: Preoperative anemia is frequent in patients undergoing orthopedic
      surgery. The purpose of this study was to assess the preoperative increase of
      hemoglobin in iron deficiency anemia patients treated with intravenous iron.
      METHODS: After obtaining written informed consent, 20 patients with iron
      deficiency anemia received 900 mg intravenous iron sucrose over 10 days starting
      4 weeks before surgery. Changes of hemoglobin and iron status were measured over
      4 weeks and at discharge. In the last 11 patients, endogenous erythropoietin was
      also measured. Data were analyzed using the Friedman test followed by pairwise
      Wilcoxon signed rank tests with Bonferroni correction. RESULTS: Hemoglobin
      increased significantly (P < 0.0001) after intravenous iron treatment. Overall,
      the mean maximum increase was 1.0 +/- 0.6 g/dl (range, 0.2-2.2 g/dl). Ferritin
      increased from 78 +/- 70 to 428 +/- 191 microg/l (P = 0.0001), ferritin index
      decreased from 2.7 +/- 2.4 to 1.5 +/- 1.0 (P = 0.0001), and soluble transferrin
      receptor decreased from 4.1 +/- 2.3 mg/l to 3.7 +/- 2.3 mg/l (P = 0.049), whereas
      transferrin saturation (20.5 +/- 9.0 to 22.9 +/- 9.0%) and serum iron (13.3 +/-
      4.6 to 13.1 +/- 4.5 microm) did not change significantly after intravenous iron
      treatment. Endogenous erythropoietin decreased from 261 +/- 130 pg/ml to 190 +/-
      49 pg/ml 2 weeks after intravenous iron treatment (P = 0.050, not significant
      after Bonferroni correction). No adverse events related to intravenous iron were
      observed. The maximum increase of hemoglobin was observed 2 weeks after the start
      of intravenous iron treatment, indicating that administration of intravenous iron
      2-3 weeks before surgery may be optimal. CONCLUSION: Treatment with intravenous
      iron allows correcting iron deficiency anemia before elective surgery.

PMID- 18043061
TI  - Quantification of epileptiform electroencephalographic activity during
      sevoflurane mask induction.
AB  - BACKGROUND: Sevoflurane may induce epileptiform electroencephalographic activity
      leading to unstable Bispectral Index numbers, underestimating the hypnotic depth
      of anesthesia. The authors developed a method for the quantification of
      epileptiform electroencephalographic activity during sevoflurane anesthesia.
      METHODS: Electroencephalographic data from 60 patients under sevoflurane mask
      induction were used in the analysis. Electroencephalographic data were visually
      classified. A novel electroencephalogram-derived quantity, wavelet subband
      entropy (WSE), was developed. WSE variables were calculated from different
      frequency bands. Performance of the WSE in detection and quantification of
      epileptiform electroencephalographic activity and the ability of the WSE to
      recognize misleading Bispectral Index readings caused by epileptiform activity
      were evaluated. RESULTS: Two WSE variables were found to be sufficient for the
      quantification of epileptiform activity: WSE from the frequency bands 4-16 and 16
      32 Hz. The lower frequency band was used for monophasic pattern monitoring, and
      the higher frequency band was used for spike activity monitoring. WSE values of
      the lower and higher bands followed the time evolution of epileptiform activity
      with prediction probabilities of 0.809 (SE, 0.007) and 0.804 (SE, 0.007),
      respectively. In deep anesthesia with epileptiform activity, WSE detected
      electroencephalographic patterns causing Bispectral Index readings greater than
      60, with event sensitivity of 97.1%. CONCLUSIONS: The developed method proved
      useful in detection and quantification of epileptiform electroencephalographic
      activity during sevoflurane anesthesia. In the future, it may improve the
      understanding of electroencephalogram-derived information by assisting in
      recognizing misleading readings of depth-of-anesthesia monitors. The method also
      may assist in minimizing the occurrence of epileptiform activity and seizures
      during sevoflurane anesthesia.

PMID- 18043062
TI  - Monitoring of the sublingual microcirculation in cardiac surgery using orthogonal
      polarization spectral imaging: preliminary results.
AB  - BACKGROUND: The recent introduction of orthogonal polarization spectral imaging
      enables the direct visualization of the microcirculation of man without imaging
      enhancing dyes. The authors studied the changes in microvascular perfusion of
      sublingual mucosa during cardiac surgery with the use of cardiopulmonary bypass
      (CPB) using this optical method. METHOD: Orthogonal polarization spectral images
      were recorded in 47 patients after skin incision (T1), after the start of CPB
      (T2), in the late phase of CPB (T3), and 1 h after the discontinuation of CPB
      (T4). The images were analyzed for microvascular diameter, erythrocyte velocity,
      and functional capillary density using an established analysis routine for
      intravital microscopy studies. In a subpopulation (n = 8), the expression of the
      adhesion molecules CD18 on circulation leukocytes was compared with the number of
      visualized rolling leukocytes. RESULTS: Preoperatively, no significant changes of
      the microvascular diameter and erythrocyte velocity were seen. The functional
      capillary density was significantly reduced at T3 to 90% of the values observed
      before CPB but recovered at T4 and showed a weak but significant correlation with
      body temperature (r = 0.38, P < 0.01) and hemoglobin concentration (r = 0.20, P <
      0.05). Expression of CD18 was significantly increased in the late phase of CPB
      (T3) only, whereas the numbers of rolling leukocytes increased during CPB and
      revealed a significant threefold increase 1 h after termination of CPB.
      CONCLUSIONS: Orthogonal polarization spectral imaging revealed no major changes
      of microvascular perfusion during uncomplicated hypothermic CPB. The slightly
      reduced functional capillary density during CPB may be caused by several factors
      all present during CPB, including hypothermia, the artificial extracorporeal
      perfusion, surgical trauma, hemodilution, and inflammatory reaction. The current
      data do not allow differentiation between the effects of those possible causes.

PMID- 18043063
TI  - Comparison of catheter-related infection and tip colonization between internal
      jugular and subclavian central venous catheters in surgical neonates.
AB  - BACKGROUND: The primary aim of this study was to compare catheter-associated
      infections and tip contaminations between percutaneously placed central venous
      catheters in the internal jugular and subclavian veins in surgical neonates
      undergoing major noncardiac surgery. METHODS: The prospectively computerized
      protocols of 295 procedures were analyzed retrospectively. RESULTS: One hundred
      twenty-nine internal jugular venous (group I) and 107 subclavian venous catheters
      (group S) were included. The median postconceptual age was 37 weeks in group I
      and 38 in group S. The weight ranged from 580 g to 4.5 kg in group I and from 820
      g to 4.5 kg in group S at the time of insertion. Significantly more catheter
      associated infections were observed in group I (15.5 vs. 4.7%; chi-square
      analysis: P < 0.01). The internal jugular venous catheters were also associated
      with a significantly increased probability of an earlier onset of a catheter
      associated infection compared with the subclavian venous catheters (log rank
      test: P < 0.01; Cox model: P < 0.01). This probability was only slightly
      increased by a lower weight (Cox model: P = 0.075), and it was not increased by a
      lower age (Cox model: P = 0.93). Significantly more catheter tips were
      contaminated by pathogens in group I (55.8 vs. 33.6%; chi-square analysis: P <
      0.01). CONCLUSION: The internal jugular venous catheters were associated with a
      higher infection rate as well as earlier onset of catheter-associated infection
      compared with the subclavian venous catheters.

PMID- 18043064
TI  - Nitrosative stress and myocardial sarcoplasmic endoreticular calcium adenosine
      triphosphatase subtype 2a activity after lung resection in swine.
AB  - BACKGROUND: Chronic, disease-associated oxidative stress induces myocardial
      peroxynitrite formation that may lead to nitrosative inhibition of the calcium
      cycling protein sarcoplasmic endoreticular calcium adenosine triphosphatase
      subtype 2a (SERCA2a). The current study was designed to test the hypothesis that
      the acute oxidative stress associated with lung resection also induces myocardial
      nitrosative stress and alters SERCA2a activity. METHODS: Ventricular myocardium
      from 16 swine was studied; 11 animals had undergone left upper lobectomy (n = 7)
      or sham thoracotomy (n = 4) 3 days before harvest, and 5 were nonoperated
      controls. Tissue peroxynitrite was assessed by measurement of 3-nitrotyrosine
      incorporation into proteins. SERCA2a activity was determined from indo-1 uptake
      by isolated sarcoplasmic reticular membranes. Expression of SERCA2a and its
      regulatory protein phospholamban were determined by Western blotting, as was the
      phospholamban phosphorylation state (when dephosporylated, phospholamban inhibits
      SERCA2a). Mechanical significance of changes in SERCA2a activity was assessed
      from the force-frequency relation of isometric myocardial trabeculae. RESULTS:
      Relative to both the control and sham groups, lobectomy animals exhibited a
      greater than twofold higher myocardial 3-nitrotyrosine incorporation and an
      approximately 50% lower SERCA2a activity, but no difference in SERCA2a or
      phospholamban expression or phospholamban phosphorylation. Concomitantly, whereas
      the trabecular force-frequency relation of control animals was positive, that of
      lobectomy animals was negative, consistent with impaired calcium cycling.
      CONCLUSIONS: These data indicate that oxidative/nitrosative stress associated
      with lung resection influences SERCA2a activity independent of any influence on
      protein expression or phospholamban phosphorylation. The findings link an acute
      event with a subcellular process primarily described for chronic illness and
      suggest a biochemical basis for perioperative changes in myocardial mechanical
      reserve.

PMID- 18043065
TI  - Isoflurane preconditioning improves long-term neurologic outcome after hypoxic
      ischemic brain injury in neonatal rats.
AB  - BACKGROUND: Preconditioning the brain with relatively safe drugs seems to be a
      viable option to reduce ischemic brain injury. The authors and others have shown
      that the volatile anesthetic isoflurane can precondition the brain against
      ischemia. Here, the authors determine whether isoflurane preconditioning improves
      long-term neurologic outcome after brain ischemia. METHODS: Six-day-old rats were
      exposed to 1.5% isoflurane for 30 min at 24 h before the brain hypoxia-ischemia
      that was induced by left common carotid arterial ligation and then exposure to 8%
      oxygen for 2 h. The neuropathology, motor coordination, and learning and memory
      functions were assayed 1 month after the brain ischemia. Western analysis was
      performed to quantify the expression of the heat shock protein 70, Bcl-2, and
      survivin 24 h after isoflurane exposure. RESULTS: The mortality was 45% after
      brain hypoxia-ischemia. Isoflurane preconditioning did not affect this mortality.
      However, isoflurane preconditioning attenuated ischemia-induced loss of neurons
      and brain tissues, such as cerebral cortex and hippocampus in the survivors.
      Isoflurane also improved the motor coordination of rats at 1 month after
      ischemia. The learning and memory functions as measured by performance of Y-maze
      and social recognition tasks in the survivors were not affected by the brain
      hypoxia-ischemia or isoflurane preconditioning. The expression of Bcl-2, a well
      known antiapoptotic protein, in the hippocampus is increased after isoflurane
      exposure. This increase was reduced by the inhibitors of inducible nitric oxide
      synthase. Inducible nitric oxide synthase inhibition also abolished isoflurane
      preconditioning-induced neuroprotection. CONCLUSIONS: Isoflurane preconditioning
      improved the long-term neurologic outcome after brain ischemia. Inducible nitric
      oxide synthase may be involved in this neuroprotection.

PMID- 18043067
TI  - Burst activation of the cerebral cortex by flash stimuli during isoflurane
      anesthesia in rats.
AB  - BACKGROUND: The degree of suppression of sensory functions during general
      anesthesia is controversial. Here, the authors investigated whether discrete
      flash stimuli induced cortical field potential responses at an isoflurane
      concentration producing burst suppression and compared the spatiotemporal
      properties and frequency spectra of flash-induced burst responses with those
      occurring spontaneously. METHODS: Rats were equipped with multiple epidural and
      intracortical electrodes to record cortical field potentials in the right
      hemisphere at several locations along the anterior-posterior axis. At isoflurane
      concentrations of 1.1, 1.4, and 1.8%, discrete light flashes were delivered to
      the left eye while cortical field potentials were continuously recorded. RESULTS:
      Isoflurane at 1.4-1.8% produced burst suppression. Each flash produced a visual
      evoked potential in the primary visual cortex followed by secondary bursting
      activity in more anterior regions. The average latency and duration of these
      bursts were 220 and 810 ms, respectively. The spontaneous and flash-induced
      bursts were similar in frequency, duration, and spatial distribution. They had
      maximum power in the frontal (primary motor) cortex with a dominant frequency of
      10 Hz. CONCLUSIONS: The results suggest that discrete flash stimuli activate the
      motor regions of the cerebral cortex during isoflurane anesthesia and that these
      activations are analogous with those that occur spontaneously during burst
      suppression. Electrocortical suppression of the cortex during anesthesia does not
      prevent its response to visual stimuli.

PMID- 18043066
TI  - An evolutionarily conserved presynaptic protein is required for isoflurane
      sensitivity in Caenorhabditis elegans.
AB  - BACKGROUND: Volatile general anesthetics inhibit neurotransmitter release by an
      unknown mechanism. A mutation in the presynaptic soluble NSF attachment protein
      receptor (SNARE) protein syntaxin 1A was previously shown to antagonize the
      anesthetic isoflurane in Caenorhabditis elegans. The mechanism underlying this
      antagonism may identify presynaptic anesthetic targets relevant to human
      anesthesia. METHODS: Sensitivity to isoflurane concentrations in the human
      clinical range was measured in locomotion assays on adult C. elegans. Sensitivity
      to the acetylcholinesterase inhibitor aldicarb was used as an assay for the
      global level of C. elegans neurotransmitter release. Comparisons of isoflurane
      sensitivity (measured by the EC50) were made by simultaneous curve fitting and F
      test as described by Waud. RESULTS: Expression of a truncated syntaxin fragment
      (residues 1-106) antagonized isoflurane sensitivity in C. elegans. This portion
      of syntaxin interacts with the presynaptic protein UNC-13, suggesting the
      hypothesis that truncated syntaxin binds to UNC-13 and antagonizes an inhibitory
      effect of isoflurane on UNC-13 function. Consistent with this hypothesis,
      overexpression of UNC-13 suppressed the isoflurane resistance of the truncated
      syntaxins, and unc-13 loss-of-function mutants were highly isoflurane resistant.
      Normal anesthetic sensitivity was restored by full-length UNC-13, by a shortened
      form of UNC-13 lacking a C2 domain, but not by a membrane-targeted UNC-13 that
      might bypass isoflurane inhibition of membrane translocation of UNC-13.
      Isoflurane was found to inhibit synaptic localization of UNC-13. CONCLUSIONS:
      These data show that UNC-13, an evolutionarily conserved protein that promotes
      neurotransmitter release, is necessary for isoflurane sensitivity in C. elegans
      and suggest that its vertebrate homologs may be a component of the general
      anesthetic mechanism.

PMID- 18043068
TI  - Sevoflurane directly excites locus coeruleus neurons of rats.
AB  - BACKGROUND: Sevoflurane, an anesthetic showing high incidence of emergence
      agitation in human patients, especially in children, increases noradrenaline
      release in the preoptic area in the rat brain. The clinically observed frequency
      of emergence agitation with sevoflurane is significantly reduced by drugs
      activating alpha2 adrenoceptors. The locus coeruleus (LC) is a source nucleus of
      widely spreading noradrenergic projections in the central nervous system and is
      also known as one of the principal targets of some alpha2-adrenoceptor agonists,
      such as dexmedetomidine. The authors analyzed the effects of sevoflurane and
      other anesthetics on the membrane current of the LC neurons to study the
      mechanism of the paradoxical "excitatory" effects of the anesthetics. METHODS:
      Effects of volatile and nonvolatile anesthetics on the membrane potential and
      currents of LC neurons in pontine slices of the rat were evaluated. Action
      potential-dependent transmission was suppressed with tetrodotoxin. RESULTS:
      Sevoflurane at 5% (measured concentration in the recording chamber, 0.5 mm)
      induced an early-phase inward current in most of LC neurons in a robust manner,
      which significantly increased the firing frequency in the absence of tetrodotoxin
      under current clamp recording. Preadministration of dexmedetomidine (1-3 nm)
      occluded this increase in firing frequency with sevoflurane. This inward current
      was inhibited by a gap junction inhibitor carbenoxolone and was not observed with
      nonvolatile general anesthetics and in non-LC neurons examined. CONCLUSIONS: The
      excitatory current activated by sevoflurane in LC neurons, likely to be mediated
      by gap junction-related mechanisms, might be one of the potential cellular
      mechanisms underlying paradoxical excitatory effect of sevoflurane.

PMID- 18043069
TI  - Return-to-duty rates among coalition forces treated in a forward-deployed pain
      treatment center: a prospective observational study.
AB  - BACKGROUND: Non-battle-related injuries and the recurrence of chronic pain are
      major causes of medical evacuation in wartime. Because a pain medicine specialist
      may or may not be assigned to a forward-deployed medical unit, the treatment of
      pain from non-battle-related injuries in war zones is a serendipitous endeavor.
      Previous studies have demonstrated that the return-to-unit rate for soldiers
      evacuated to a tertiary care facility for pain management is abysmally low.
      METHODS: This is a prospective, observational study measuring return-to-duty
      rates in the first forward-deployed pain treatment center. RESULTS: Over a 6
      month period, 132 patients were treated, the large majority (n = 113) of whom
      were coalition forces. In descending order, the four most common diagnoses among
      coalition forces were lumbar radiculopathy (n = 63), thoracic pain (n = 13),
      cervical radiculopathy (n = 8), and groin pain (n = 8). Epidural steroid
      injections (n = 125) were by far the most frequently performed procedure,
      followed by trigger point injections (n = 21), lumbar facet blocks (n = 16), and
      groin blocks (n = 9). Nonsteroidal antiinflammatory drugs were prescribed to 70%
      of patients, and 24% were referred to physical therapy. The return-to-duty rate
      for coalition forces was 94.7%. The primary complaint of all 7 patients who
      required medical evacuation outside the theaters of operation was groin pain.
      CONCLUSIONS: These results demonstrate the feasibility of obtaining high return
      to-duty rates when aggressive pain management strategies are used in forward
      deployed areas.

PMID- 18043070
TI  - Neurokinin-1 receptor antagonists inhibit the recruitment of opioid-containing
      leukocytes and impair peripheral antinociception.
AB  - BACKGROUND: Neurokinins (e.g., substance P) contribute to pain transmission in
      the central nervous system, peripheral neurogenic inflammation, and leukocyte
      recruitment in inflammation. Leukocyte recruitment involves (1) up-regulation of
      adhesion molecule expression through neurokinin-1 (NK1) receptors on endothelial
      cells, (2) augmented chemokine production, or (3) chemotaxis through NK1
      receptors on leukocytes. In inflammation, leukocytes can trigger endogenous
      antinociception through release of opioid peptides and activation of opioid
      receptors on peripheral sensory neurons. The authors hypothesized that NK1
      receptor antagonists impair recruitment of opioid-containing leukocytes and
      stress-induced antinociception. METHODS: Rats were treated intraperitoneally and
      intrathecally with peripherally restricted (SR140333) or blood-brain barrier
      penetrating (L-733,060) NK1 receptor antagonists and were evaluated for paw
      pressure thresholds, numbers of infiltrating opioid-containing leukocytes and
      leukocyte subpopulations, expression of adhesion molecules, NK1 receptors, and
      chemokines 24-48 h after complete Freund adjuvant-induced hind paw inflammation.
      RESULTS: Systemic and peripherally selective, but not intrathecal, NK1 receptor
      blockade reduced stress-induced antinociception (control: 177 +/- 9 g, L-733,060:
      117 +/- 8 g, and control: 166 +/- 30 g, SR140333: 89 +/- 3 g; both P < 0.05, t
      test) without affecting baseline hyperalgesia. In parallel, local recruitment of
      opioid-containing leukocytes was decreased (L-733,060 and SR140333: 56.0 +/- 4.3
      and 59.1 +/- 7.9% of control; both P < 0.05, t test). NK1 receptors were
      expressed on peripheral neurons, infiltrating leukocytes and endothelial cells.
      Peripheral NK1 receptor blockade did not alter endothelial expression of
      intercellular adhesion molecule-1 or local chemokine and cytokine production, but
      decreased polymorphonuclear cell and macrophage recruitment. CONCLUSIONS:
      Endogenous inhibition of inflammatory pain is dependent on NK1 receptor-mediated
      recruitment of opioid-containing leukocytes.

PMID- 18043071
TI  - New frontiers in the evaluation of cardiac patients for noncardiac surgery.

PMID- 18043073
TI  - Clarifying equipment specifications and performance characteristics.

PMID- 18043074
TI  - Can 1% sevoflurane with 5 ng/ml remifentanil prevent implicit memory?

PMID- 18043075
TI  - Does combined epidural-general anesthesia increase risk over either technique
      used alone?

PMID- 18043077
TI  - Perioperative central venous cannulation: it is time for action.

PMID- 18043078
TI  - Medication error: a leading cause of anesthesia-related morbidity and mortality.

PMID- 18043081
TI  - Epidural complications across the globe.

PMID- 18043083
TI  - Etomidate unlikely to have induced pacemaker-mediated tachycardia.

PMID- 18043085
TI  - Potential hazard associated with a laryngoscope blade.

PMID- 18043086
TI  - Misleading behavior of Masimo pulse oximeter tone during profound bradycardia.

PMID- 18043091
TI  - Why should young doctors choose to become surgeons?

PMID- 18043092
TI  - Long-term results of intersphincteric resection for low rectal cancer.
AB  - INTRODUCTION: In the treatment of very low rectal cancer, a distal resection
      margin of more than 1 cm can be obtained by partial internal sphincteric
      resection, allowing a sphincter preserving surgery. Thus, intersphincteric
      resection (ISR) has been proposed as an alternative to abdominoperineal resection
      for selected low rectal cancer. OBJECTIVE: The aim of our study was to assess the
      morbidity, mortality, and the long-term oncologic and functional results of ISR.
      METHODS: Charts of patients who had ISR between 1992 and 2004 were reviewed.
      Cancer-related survival and locoregional recurrence rates were calculated using
      the Kaplan-Meier method. Functional outcome was assessed by using a standardized
      gastrointestinal functional questionnaire. Incontinence was assessed by the
      continence score of Wexner. RESULTS: Ninety patients (59 males, 31 females) with
      a tumor at a median distance of 35 mm (range, 22-52) from the anal verge had an
      ISR. Thirty-seven patients (41%) had preoperative radiotherapy. Histologically
      complete remission after neoadjuvant radiotherapy (ypT0) was observed in 7
      patients (8%), 12 patients (13%) were pT1, 35 patients (39%) pT2, 32 patients
      (36%) pT3, and 4 patients (4%) pT4. Five patients (5.5%) had synchronous liver
      metastases. R0 resection was obtained in 85 patients (94.4%). The median distal
      resection margin on the fixed specimen was 12 mm (range, 5-35) and was positive
      in 1 case. The circumferential margin was positive (< or =1 mm) in 4 patients
      (4.4%). There was no mortality. Complication rate was 18.8%: anastomotic leakage
      occurred in 8 patients (8.8%) and 1 patient had an anovaginal fistula. Five
      patients (5.6%) underwent secondary abdominoperineal resection: 1 for positive
      distal margin, 1 for colonic J-pouch necrosis, and 3 for local recurrence.
      ONCOLOGIC RESULTS: After a median follow-up of 56.2 months (range, 13.3-168.4),
      local, distant, and combined recurrence occurred in 6 (6.6%), 8 (8.8%), and 2
      patients, respectively. Thirteen patients (14.4%) died of cancer recurrence. Five
      year overall and disease-free survival was 82% (80-97) and 75% (64-86),
      respectively. In univariate analysis, overall survival was significantly
      influenced by pTNM stage and T stage (pT 1-2 vs. 3-4: P = 0.008 and stage I-II
      vs. III-IV: P = 0.03). In multivariate analysis, we did not find any impact on
      local recurrence-free survival for the investigated prognostic variables.
      FUNCTIONAL RESULTS: For a total of 83 patients the mean stool frequency was 2.3
      +/- 1.3 per 24 hours. Forty-one percent of patients had stool fragmentation, one
      third nocturnal defecation, 19% fecal urgency, and 36% followed low fiber diet.
      Thirty-four patients (41%) were fully continent, 29 patients (35%) had minor
      continence problems, and 20 patients (24%) were incontinent. After adjustment for
      age, gender, tumor level, and pTNM stage, preoperative radiotherapy was the only
      factor associated with a risk of fecal incontinence [OR (IC 95%) = 3.1 (1.0-9.0),
      P = 0.04]. CONCLUSION: In selected patients, ISR is a safe operation with good
      oncologic results. It achieves good functional results in 76% of patients.
      Functional results are significantly altered by preoperative radiotherapy.

PMID- 18043093
TI  - Pancreatic head resection with segmental duodenectomy: safety and long-term
      results.
AB  - OBJECTIVE: To evaluate the usefulness and long-term results with pancreatic head
      resection with segmental duodenectomy (PHRSD; Nakao's technique) in patients with
      branch-duct type intraductal papillary mucinous neoplasms (IPMNs). A prospective
      study from Nagoya (Japan) and Barcelona (Spain). SUMMARY BACKGROUND DATA: Surgery
      should be the first choice of treatment of IPMNs. An aggressive surgery (eg,
      pancreatoduodenectomy) should be questioned in patients with an indolent disease
      or with noninvasive tumors. Recently, organ-preserving pancreatic resections for
      benign and noninvasive IPMN located in the head of the pancreas have been
      described. We have PHRSD in which the pancreatic head can be completely resected
      and the major portion of the duodenum can be preserved by this procedure. There
      have been only 4 reports concerning PHRSD with <8 patients (each one) in the
      English literature. METHODS: Thirty-five patients underwent PHRSD (20 men, 15
      women), mean age 65.1 +/- 9.0 (range, 55-75). Mean maximal diameter of the cystic
      lesion was 26.4 +/- 5.3 mm (range, 20-33 mm) and mean diameter of the main
      pancreatic duct was 3.3 +/- 0.5 mm (range, 3.0-4.0 mm). Alimentary tract
      reconstruction was performed in 20 patients by pancreatogastrostomy,
      duodenoduodenostomy, and choledochoduodenostomy (type A) and 15 patients by
      pancreaticojejunostomy, duodenoduodenostomy and choledochojejunostomy (Roux-en-Y;
      type B). Surgical parameters, postoperative complications, endocrine function,
      exocrine function, and long-term outcomes were evaluated. To compare the
      perioperative factors, a matched-pairs analysis between PHRSD patients and
      patients with pylorus preserving pancreaticoduodenectomy (PPPD) was performed. In
      the latter group were included 32 patients with branch-duct type of IPMN operated
      during the same time period that patients with PHRSD. The mean follow-up period
      was 48.8 months. RESULTS: Mean operative time after PHRSD was 365 +/- 50 and mean
      surgical blood loss was 615 +/- 251 mL. There was no mortality. Pancreatic
      fistula occurred in 10% and 13% with types (alimentary tract reconstruction) A
      and B, respectively. Noninvasive IPMN was found in 31 patients and invasive IPMN
      in 4 patients (11.4%). In the matched-pairs analysis between PHRSD and PPPD, the
      2 procedures were comparable in regard to operation time and intraoperative blood
      loss. The overall incidence of pancreatic fistula was higher after PPPD than
      after PHRSD; the difference was not statistically significant. When fistulas
      occurred after PHRSD they were grade A (biochemical). In contrast, pancreatic
      fistulas after PPPD were grade A in 78% of cases and grade B in 22% (clinically
      relevant fistula). The incidence of delayed gastric emptying was significantly
      higher in the PPPD group compared with the PHRSD group (P < 0.01). Endocrine
      pancreatic function, measured by fasting blood glucose levels and HbA1, levels
      was unchanged in 94.28% of patients, in the PHRSD group, and in 87.87% in the
      PPPD group. Body weight was unchanged in 80% after PHRSD and in 59% after PPPD.
      Postoperative enzyme substitution was needed in 20% of patients after PHRSD and
      in 40% patients after PPPD. The 5-year survival rate was 100% in patients with
      benign IPMN and 42% in patients with invasive IPMN. CONCLUSION: PHRSD is a safe
      and reasonable technique appropriate for selected patients with branch-duct IPMN.
      The major advantages of PHRSD are promising long-term results in terms of
      pancreatic function (exocrine and endocrine) with important consequences in
      elderly patients. Long-term outcome was satisfactory without tumor recurrence in
      noninvasive carcinoma. PHRSD should therefore be considered as an adequate
      operation as an organ-preserving pancreatic resection for branch-duct type of
      IPMN located at the head of the pancreas.

PMID- 18043094
TI  - 18-fluorodeoxyglucose positron emission tomography enhances computed tomography
      diagnosis of malignant intraductal papillary mucinous neoplasms of the pancreas.
AB  - OBJECTIVE: To assess the reliability of 18-fluorodeoxyglucose positron emission
      tomography (18-FDG PET) in distinguishing benign from malignant intraductal
      papillary mucinous neoplasms (IPMNs) of the pancreas and its contribution to
      surgical decision making. SUMMARY BACKGROUND DATA: Pancreatic IPMNs are
      increasingly recognized, often as incidental findings, especially in people over
      age 70 and 80. Computed tomography (CT) and magnetic resonance (MR) are
      unreliable in discriminating a benign from a malignant neoplasm. 18-FDG PET as
      imaging procedure based on the increased glucose uptake by tumor cells has been
      suggested for diagnosis and staging of pancreatic cancer. METHODS: From January
      1998 to December 2005, 64 patients with suspected IPMNs were prospectively
      investigated with 18-FDG PET in addition to conventional imaging techniques
      [helical-CT in all and MR and magnetic resonance cholangiopancreatography (MRCP)
      in 60]. 18-FDG PET was analyzed visually and semiquantitatively using the
      standard uptake value (SUV). The validation of the diagnosis was made by a
      surgical procedure (n = 44), a percutaneous biopsy (n = 2), main duct cytology (n
      = 1), or follow-up (n = 17). Mean and median follow-up times were 25 and 27.5
      months, respectively (range, 12-90 months). RESULTS: Twenty-seven patients (42%)
      were asymptomatic. Forty-two patients underwent pancreatic resection, 2
      palliative surgery, and 20 did not undergo surgery. An adenoma was diagnosed in
      13 patients, a borderline tumor in 8, a carcinoma in situ in 5, and an invasive
      cancer in 21; in 17 patients a tumor sampling was not performed and therefore the
      histology remained undetermined. Positive criteria of increased uptake on 18-FDG
      PET was absent in 13 of 13 adenomas and 7 of 8 borderline IPMNs, but was present
      in 4 of 5 carcinoma in situ (80%) and in 20 of 21 invasive cancers (95%).
      Conventional imaging technique was strongly suggestive of malignancy in 2 of 5
      carcinomas in situ and in 13 of 21 invasive carcinomas (62%). Furthermore,
      conventional imaging had findings that would be considered falsely positive in 1
      of 13 adenomas (8%) and in 3 of 8 borderline neoplasms (37.5%). Therefore,
      positive 18-FDG PET influenced surgical decision making in 10 patients with
      malignant IPMN. Furthermore, negative findings on 18-FDG PET prompted us to use a
      more limited resection in 15 patients, and offered a follow-up strategy in 18
      patients (3 positive at CT scan) for the future development of a malignancy.
      CONCLUSIONS: 18-FDG PET is more accurate than conventional imaging techniques (CT
      and MR) in distinguishing benign from malignant (invasive and noninvasive) IPMNs.
      18-FDG PET seems to be much better than conventional imaging techniques in
      selecting IPMNs patients, especially when old and asymptomatic, for surgical
      treatment or follow-up.

PMID- 18043095
TI  - Use of severely steatotic grafts in liver transplantation: a matched case-control
      study.
AB  - BACKGROUND: Although there is a worldwide need to expand the pool of available
      liver grafts, cadaveric livers with severe steatosis (>60%) are discarded for
      orthotopic liver transplantation (OLT) by most centers. METHODS: We analyzed
      patients receiving liver grafts with severe steatosis between January 2002 and
      September 2006. These patients were matched 1:2 with control patients without
      severe steatosis according to status the waiting list, recipient age, recipient
      body mass index (BMI), and model for end-stage liver disease (MELD) score.
      Primary end points were the incidence of primary graft nonfunction (PNF), and
      graft and patient survival. Secondary end points included primary graft
      dysfunction (PDF), the incidence of postoperative complications, and histologic
      assessment of steatosis in follow-up biopsies. We also conducted a survey on the
      use of grafts with severe steatosis among leading European liver transplant
      centers. RESULTS: During the study period, 62 patients dropped out of the waiting
      list and 45 of them died due to progression of disease. Of 118 patients who
      received transplants 20 (17%) received a graft with severe steatosis during this
      period. The median degree of total liver steatosis was 90% (R = 65%-100%) for the
      steatotic group. The steatotic (n = 20) and matched control group (n = 40) were
      comparable in terms of recipient age, BMI, MELD score, and cold ischemia time.
      The steatotic group had a significantly higher rate of PDF and/or renal failure.
      Although the median intensive care unit (ICU) and hospital stay were not
      significantly different between both groups, the proportion of patients with long
      term ICU (> or =21 days) and hospital (> or =40 days) stay was significantly
      higher for patients with a severely steatotic graft. Sixty-day mortality (5% vs.
      5%) and 3-year patient survival rate (83% vs. 84%) were comparable between the
      control and severe steatosis group. Postoperative histologic assessment
      demonstrated that the median total amount of liver steatosis decreased
      significantly (median: 90% to 15%, P < 0.001). Our survey showed that all but one
      of the European centers currently reject liver grafts with severe steatosis for
      any recipient. CONCLUSION: Due to the urgent need of liver grafts, severely
      steatotic grafts should be no longer discarded for OLT. Maximal effort must be
      spent when dealing with these high-risk organs but the use of severely steatotic
      grafts may save the lives of many patients who would die on the waiting list.

PMID- 18043096
TI  - The place of liver transplantation in the treatment of hepatic epitheloid
      hemangioendothelioma: report of the European liver transplant registry.
AB  - BACKGROUND: Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade
      vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of
      larger clinical experiences with detailed long-term follow-up. MATERIAL AND
      METHODS: Fifty-nine patients, reported to the European Liver Transplant Registry,
      were analyzed to define the role of liver transplantation (LT) in the treatment
      of this disease. Eleven (19%) patients were asymptomatic. Eighteen (30.5%)
      patients had pre-LT surgical [hepatic (7 patients) and extrahepatic (3 patients)]
      and/or systemic or locoregional (10 patients) medical therapy. Ten (16.9%)
      patients had extrahepatic disease localization before or at the time of LT.
      Follow-up was complete for all patients with a median of 92.5 (range, 7-369) from
      moment of diagnosis and a median of 78.5 (range, 1-245) from the moment of LT.
      RESULTS: HEHE was bilobar in 96% of patients; 86% of patients had more than 15
      nodules in the liver specimen. Early (<3 months) and late (>3 months) post-LT
      mortality was 1.7% (1 patient) and 22% (14 patients). Fourteen (23.7%) patients
      developed disease recurrence after a median time of 49 months (range, 6-98). Nine
      (15.3%) patients died of recurrent disease and 5 are surviving with recurrent
      disease. One-, 5-, and 10- year patient survival rates from moment of
      transplantation for the whole series are 93%, 83%, 72%. Pre-LT tumor treatment (n
      = 18) (89%, 89%, and 68% 1-, 5-, and 10-year survival rates from moment of LT vs.
      95%, 80%, and 73% in case of absence of pre-LT treatment), lymph node (LN)
      invasion (n = 18) (96%, 81%, and 71% 1-, 5-, and 10-year survival rates vs. 83%,
      78%, and 67% in node negative patients) and extrahepatic disease localization (n
      = 10) (90%, 80%, and 80% 1-, 5-, and 10-year survival rates vs. 94%, 83%, and 70%
      in case of absence of extrahepatic disease) did not significantly influence
      patient survival whereas microvascular (n = 24) (96%, 75%, 52% 1-, 5-, and 10
      year survival vs. 96%, 92%, 85% in case of absence of microvascular invasion) and
      combined micro- and macrovascular invasion (n = 28) (90%, 72%, and 54% 1-,5-, and
      10-year survival vs. 96%, 92%, and 85% in case of absence of vascular invasion, P
      = 0.03) did. Disease-free survival rates at 1, 5, and 10 years post-LT are 90%,
      82%, and 64%. Disease-free survival is not significantly influenced by pre-LT
      treatment, LN status, extrahepatic disease localization, and vascular invasion.
      CONCLUSIONS: The results of the largest reported transplant series in the
      treatment of HEHE are excellent. Preexisting extrahepatic disease localization as
      well as LN involvement are not contraindications to LT. Microvascular or combined
      macro-microvascular invasion significantly influence survival after LT. LT
      therefore should be offered as a valid therapy earlier in the disease course of
      these, frequently young, patients. Recurrent (allograft) disease should be
      treated aggressively as good long-term survivals can be obtained. Long-term
      prospective follow-up multicenter studies as well as the evaluation of
      antiangiogenic drugs are necessary to further optimize the treatment of this rare
      vascular hepatic disorder.

PMID- 18043097
TI  - Localized hepatic ischemia after liver resection: a prospective evaluation.
AB  - OBJECTIVE: To prospectively assess the frequency, severity, and extension of
      localized ischemia in the remaining liver parenchyma after hepatectomy.
      BACKGROUND: Major blood loss and postoperative ischemia of the remnant liver are
      known factors contributing to morbidity after liver surgery. The segmental
      anatomy of the liver and the techniques of selective hilar or suprahilar clamping
      of the Glissonian sheaths permit identification of ischemia on the surface of the
      corresponding segments for precise section of the parenchyma. Incomplete
      resection of a segment, or compromised blood supply to the remaining liver, may
      result in ischemia of various extension and severity. METHODS: Patients
      undergoing hepatectomy received enhanced computerized tomodensitometry with study
      of the arterial and venous phases within 48 hours after resection. We defined
      hepatic ischemia as reduced or absent contrast enhancement during the venous
      phase. We classified the severity of ischemia as hypoperfusion, nonperfusion, or
      necrosis. The extension of ischemia was identified as marginal, partial, or
      segmental. Factors that may influence postoperative ischemia were analyzed by
      univariate and multivariate analyses. RESULTS: One hundred fifty consecutive
      patients (70 F, 80 M, mean age 62 +/- 12 years) underwent 64 major and 81 minor
      hepatectomies and 5 wedge resections. We observed radiologic signs of ischemia in
      38 patients (25.3%): 33 hypoperfusions (17 marginal, 12 partial, and 4
      segmental), 3 nonperfusions (1 marginal, 1 partial, and 1 segmental), and 2
      necroses (1 partial, 1 segmental). One patient with a segmental necrosis
      underwent an early reoperation. In all other cases, the evolution was
      spontaneously favorable. Postoperative peak levels of serum aspartate
      aminotransferase and alanine aminotransferase were significantly higher in
      patients with ischemia. Patients with ischemia had a significantly higher risk of
      developing a biliary leak (18.4% vs. 2.6%, P < 0.001). There was no correlation
      between liver ischemia and mortality (2%). None of the following factors were
      associated with ischemia after univariate and multivariate analysis: age,
      preoperative bilirubin level, liver fibrosis, malignant tumor, type of
      hepatectomy, surface of transection, weight of resected liver, Pringle maneuver,
      blood loss, and number of transfusions. CONCLUSIONS: Some form of localized
      ischemia after hepatectomy was detected in 1 of 4 of our patients. Its clinical
      expression was discreet in the large majority of cases, even if it might have
      been one of the underlying causes of postoperative biliary fistulas. Clinical
      observation is sufficient to detect the rare patient with suspected postoperative
      liver ischemia that will require active treatment.

PMID- 18043098
TI  - Is there still a role for total pancreatectomy?
AB  - OBJECTIVE: To evaluate the perioperative and long-term results of total
      pancreatectomy (TP), and to assess whether it provides morbidity, mortality, and
      quality of life (QoL) comparable to those of the pylorus-preserving (pp)-Whipple
      procedure in patients with benign and malignant pancreatic disease. SUMMARY
      BACKGROUND DATA: TP was abandoned for decades because of high peri- and
      postoperative morbidity and mortality. Because selected pancreatic diseases are
      best treated by TP, and pancreatic surgery and postoperative management of
      exocrine and endocrine insufficiency have significantly improved, the hesitance
      to perform a TP is disappearing. PATIENTS AND METHODS: In a prospective study
      conducted from October 2001 to November 2006, all patients undergoing a TP (n =
      147; 100 primary elective TP [group A], 24 elective TP after previous pancreatic
      resection [group B], and 23 completion pancreatectomies for complications) were
      included, and perioperative and late follow-up data, including the QoL (EORTC QLQ
      C30 questionnaire), were evaluated. A matched-pairs analysis with patients
      receiving a pp-Whipple operation was performed. RESULTS: Indications for an
      elective TP (group A + B) were pancreatic and periampullary adenocarcinoma (n =
      71), other neoplastic pancreatic tumors (intraductal papillary mucinous
      neoplasms, neuroendocrine tumors, cystic tumors; n = 34), metastatic lesions (n =
      8), and chronic pancreatitis (n = 11). There were 73 men and 51 women with a mean
      age of 60.9 +/- 11.3 years. Median intraoperative blood loss was 1000 mL and
      median operation time was 380 minutes. Postoperative surgical morbidity was 24%,
      medical morbidity was 15%, and mortality was 4.8%. The relaparotomy rate was 12%.
      Median postoperative hospital stay was 11 days. After a median follow-up of 23
      months, global health status of TP patients was comparable to that of pp-Whipple
      patients, although a few single QoL items were reduced. All patients required
      insulin and exocrine pancreatic enzyme replacements. The mean HbA1c value was
      7.3% +/- 0.9%. CONCLUSION: In this cohort study, mortality and morbidity rates
      after elective TP are not significantly different from the pp-Whipple. Because of
      improvements in postoperative management, QoL is acceptable, and is almost
      comparable to that of pp-Whipple patients. Therefore, TP should no longer be
      generally avoided, because it is a viable option in selected patients.

PMID- 18043099
TI  - Unilateral versus bilateral neck exploration for primary hyperparathyroidism:
      five-year follow-up of a randomized controlled trial.
AB  - OBJECTIVE: To compare long-term patient outcome in a prospective randomized
      controlled trial between unilateral and bilateral neck exploration for primary
      hyperparathyroidism (pHPT). SUMMARY BACKGROUND DATA: Minimal invasive and/or
      focused parathyroidectomy has challenged the traditional bilateral neck
      exploration for pHPT. Between 1997 and 2001, we conducted the first unselected
      randomized controlled trial of unilateral versus bilateral neck exploration for
      pHPT. The results showed that unilateral exploration is a surgical strategy with
      distinct advantages in the early postoperative period. However, concerns have
      been raised that limited parathyroid exploration could increase the risk for
      recurrent pHPT during long-term follow-up. METHODS: Ninety-one patients with the
      diagnosis of pHPT were randomized to unilateral or bilateral neck exploration.
      Preoperative scintigraphy and intraoperative parathyroid hormone measurement
      guided the unilateral exploration. Gross morphology and frozen section determined
      the extent of parathyroid tissue resection in the bilateral group. Follow-up was
      performed after 6 weeks, 1 year, and 5 years postoperatively. RESULTS: Seventy
      one patients were available for 5-year follow-up. There were no differences in
      serum ionized calcium and parathyroid hormone, respectively, between patients in
      the unilateral and bilateral group. Overall 6 patients have been found to have
      persistent (n = 3) or recurrent (n = 3) pHPT; 4 patients in the unilateral group
      (3 of these 4 patients were bilaterally explored) and 2 patients in the bilateral
      group. Three of 6 failures were unexpectedly found to have multiple endocrine
      neoplasia mutations. One patient with solitary adenoma in the bilateral group
      still required vitamin D substitution 5 years after surgery. CONCLUSION:
      Unilateral neck exploration with intraoperative parathyroid hormone assessment
      provides the same long-term results as bilateral neck exploration, and is thus a
      valid strategy for the surgical treatment of pHPT.

PMID- 18043100
TI  - Improved kidney graft function after preservation using a novel hypothermic
      machine perfusion device.
AB  - OBJECTIVE: To study graft function and ischemia/reperfusion injury of porcine
      kidneys after preservation with the new Groningen Machine Perfusion (GMP) system
      versus static cold storage (CS). INTRODUCTION: The increasing proportion of
      marginal and nonheart beating donors necessitates better preservation methods to
      maintain adequate graft viability. Hypothermic machine preservation (HMP) is a
      promising alternative to static CS. We have therefore developed and tested an HMP
      device, which is portable and actively oxygenates the perfusate via an
      oxygenator. The aim of the present study was to examine the efficacy of the GMP
      system in a transplantation experiment. MATERIALS AND METHODS: In a porcine
      autotransplantation model, kidneys were retrieved and either cold stored in
      University of Wisconsin CS for 20 hours at 4 degrees C or subjected to HMP using
      University of Wisconsin machine perfusion at 4 degrees C with 2 different
      pressure settings: 30/20 mm Hg or 60/40 mm Hg. RESULTS: HMP at 30/20 mm Hg was
      found to better preserve the viability of kidneys reflected by improved cortical
      microcirculation, less damage to the proximal tubule, less damage mediated by
      reactive oxygen species, less proinflammatory cytokine expression, and better
      functional recovery after transplantation. However, high perfusion pressures
      (60/40 mm Hg) resulted in higher expression of von Willebrand factor and monocyte
      chemotactic peptide-1 in postpreservation biopsies and subsequent graft
      thrombosis in 2 kidneys. CONCLUSIONS: It is concluded that the GMP system
      improves kidney graft viability and perfusion pressures are critically important
      for outcome.

PMID- 18043101
TI  - Extended transthoracic resection compared with limited transhiatal resection for
      adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized
      clinical trial.
AB  - OBJECTIVE: To determine whether extended transthoracic esophagectomy for
      adenocarcinoma of the mid/distal esophagus improves long-term survival.
      BACKGROUND: A randomized trial was performed to compare surgical techniques.
      Complete 5-year survival data are now available. METHODS: A total of 220 patients
      with adenocarcinoma of the distal esophagus (type I) or gastric cardia involving
      the distal esophagus (type II) were randomly assigned to limited transhiatal
      esophagectomy or to extended transthoracic esophagectomy with en bloc
      lymphadenectomy. Patients with peroperatively irresectable/incurable cancer were
      excluded from this analysis (n = 15). A total of 95 patients underwent
      transhiatal esophagectomy and 110 patients underwent transthoracic esophagectomy.
      RESULTS: After transhiatal and transthoracic resection, 5-year survival was 34%
      and 36%, respectively (P = 0.71, per protocol analysis). In a subgroup analysis,
      based on the location of the primary tumor according to the resection specimen,
      no overall survival benefit for either surgical approach was seen in 115 patients
      with a type II tumor (P = 0.81). In 90 patients with a type I tumor, a survival
      benefit of 14% was seen with the transthoracic approach (51% vs. 37%, P = 0.33).
      There was evidence that the treatment effect differed depending on the number of
      positive lymph nodes in the resection specimen (test for interaction P = 0.06).
      In patients (n = 55) without positive nodes locoregional disease-free survival
      after transhiatal esophagectomy was comparable to that after transthoracic
      esophagectomy (86% and 89%, respectively). The same was true for patients (n =
      46) with more than 8 positive nodes (0% in both groups). Patients (n = 104) with
      1 to 8 positive lymph nodes in the resection specimen showed a 5-year
      locoregional disease-free survival advantage if operated via the transthoracic
      route (23% vs. 64%, P = 0.02). CONCLUSION: There is no significant overall
      survival benefit for either approach. However, compared with limited transhiatal
      resection extended transthoracic esophagectomy for type I esophageal
      adenocarcinoma shows an ongoing trend towards better 5-year survival. Moreover,
      patients with a limited number of positive lymph nodes in the resection specimen
      seem to benefit from an extended transthoracic esophagectomy.

PMID- 18043102
TI  - Mortality after bariatric surgery: analysis of 13,871 morbidly obese patients
      from a national registry.
AB  - OBJECTIVE: To define mortality rates and risk factors of different bariatric
      procedures and to identify strategies to reduce the surgical risk in patients
      undergoing bariatric surgery. SUMMARY BACKGROUND DATA: Postoperative mortality is
      a rare event after bariatric surgery. Therefore, comprehensive data on mortality
      are lacking in the literature. METHODS: A retrospective analysis of a large
      prospective database was carried out. The Italian Society of Obesity Surgery runs
      a National Registry on bariatric surgery where all procedures performed by
      members of the Society should be included prospectively. This Registry represents
      at present the largest database on bariatric surgery worldwide. RESULTS: Between
      January 1996 and January 2006, 13,871 bariatric surgical procedures were
      included: 6122 adjustable silicone gastric bandings (ASGB), 4215 vertical banded
      gastroplasties (VBG), 1106 gastric bypasses, 1988 biliopancreatic diversions
      (BPD), 303 biliointestinal bypasses, and 137 various procedures. Sixty day
      mortality was 0.25%. The type of surgical procedure significantly influenced (P <
      0.001) mortality risk: 0.1% ASGB, 0.15% VBG, 0.54% gastric bypasses, 0.8% BPD.
      Pulmonary embolism represented the most common cause of death (38.2%) and was
      significantly higher in the BPD group (0.4% vs. 0.07% VBG and 0.03% ASGB). Other
      causes of mortality were the following: cardiac failure 17.6%, intestinal leak
      17.6%, respiratory failure 11.8%, and 1 case each of acute pancreatitis, cerebral
      ischemia, bleeding gastric ulcer, intestinal ischemia, and internal hernia.
      Therefore, 29.4% of patients died as a result of a direct technical complication
      of the procedure. Additional significant risk factors included open surgery (P <
      0.001), prolonged operative time (P < 0.05), preoperative hypertension (P < 0.01)
      or diabetes (P < 0.05), and case load per Center (P < 0.01). CONCLUSIONS:
      Mortality after bariatric surgery is a rare event. It is influenced by different
      risk factors including type of surgery, open surgery, prolonged operative time,
      comorbidities, and volume of activity. In defining the best bariatric procedure
      for each patient the different mortality risks should be taken into account.
      Choice of the procedure, prevention, early diagnosis, and therapy for
      cardiovascular complications may reduce postoperative mortality.

PMID- 18043103
TI  - Open right colectomy is still effective compared to laparoscopy: results of a
      randomized trial.
AB  - OBJECTIVE: The primary goal of this study was to clarify whether a laparoscopic
      (LPS) approach could be considered the dominant strategy in patients undergoing
      right colectomy. SUMMARY BACKGROUND DATA: Because few nonrandomized or small
      sized studies have been carried out so far, definitive conclusions about the role
      of LPS right colectomy cannot be drawn. METHODS: Two hundred twenty-six patients,
      candidates for right colectomy, were randomly assigned to LPS (n = 113) or open
      (n = 113) resection. The postoperative care protocol was the same for both
      groups. Trained members of the surgical staff who were not involved in the study
      registered postoperative morbidity. Follow-up was carried out for 30 days after
      hospital discharge. The following costs were calculated: surgical instruments,
      operative room occupation, routine care, postoperative morbidity, and
      hospitalization. RESULTS: Conversion rate in the LPS group was 2.6% (3 of 113).
      Operative time (in minutes) was longer in the LPS group (131 vs. 112, P = 0.01).
      Postoperative morbidity rate was 18.6% in the open group and 13.3% in the LPS
      group (P = 0.31). Postoperative stay was one day longer in the open group (P =
      0.002). No difference was found in postoperative quality of life. The additional
      operative charge in the LPS group was euro980 per patient randomized (euro821 for
      surgical instruments and euro159 for longer operative time). The savings in the
      LPS group was euro390 per patient randomized (euro144 for shorter length of
      hospital stay and euro246 for the lower cost of postoperative morbidity). The net
      balance resulted in a euro590 extra charge per patient randomly allocated to the
      LPS group. CONCLUSION: LPS slightly improved postoperative recovery. This
      translated into a savings that covered only 40% of the extra operative charge.
      Therefore, open right colectomy could be still considered an effective procedure.

PMID- 18043104
TI  - Randomized trial of argon plasma coagulation versus endoscopic surveillance for
      barrett esophagus after antireflux surgery: late results.
AB  - OBJECTIVE: To determine the efficacy of endoscopic argon plasma coagulation (APC)
      for ablation of Barrett esophagus. SUMMARY BACKGROUND DATA: APC has been used to
      ablate Barrett esophagus. However, the long-term outcome of this treatment is
      unknown. This study reports 5-year results from a randomized trial of APC versus
      surveillance for Barrett esophagus in patients who had undergone a fundoplication
      for the treatment of gastroesophageal reflux. METHODS: Fifty-eight patients with
      Barrett esophagus were randomized to undergo either ablation using APC or ongoing
      surveillance. At a mean 68 months after treatment, 40 patients underwent
      endoscopy follow-up. The efficacy of treatment, durability of the neosquamous re
      epithelialization, and safety of the procedure were determined. RESULTS:
      Initially, at least 95% ablation of the metaplastic mucosa was achieved in all
      treated patients. At the 5-year follow-up, 14 of 20 APC patients continued to
      have at least 95% of their previous Barrett esophagus replaced by neosquamous
      mucosa, and 8 of these had complete microscopic regression of the Barrett
      esophagus. Five of the 20 surveillance patients had more than 95% regression of
      their Barrett esophagus, and 4 of these had complete microscopic regression (1
      after subsequent APC treatment). The length of Barrett esophagus shortened
      significantly in both study groups, although the extent of regression was greater
      after APC treatment (mean 5.9-0.8 cm vs. 4.6-2.2 cm). Two patients who had
      undergone APC treatment developed a late esophageal stricture, which required
      endoscopic dilation, and 2 patients in the surveillance group developed high
      grade dysplasia during follow-up. CONCLUSIONS: Regression of Barrett esophagus
      after fundoplication is more likely, and greater in extent, in patients who
      undergo ablation with APC. In most patients treated with APC the neosquamous
      mucosa remains stable at up to 5-year follow-up. The development of high-grade
      dysplasia only occurred in patients who were not treated with APC.

PMID- 18043105
TI  - Laparoscopic surgery is associated with a lower incidence of venous
      thromboembolism compared with open surgery.
AB  - BACKGROUND: Although laparoscopy now plays a major role in most general surgical
      procedures, little is known about the relative risk of venous thromboembolism
      (VTE) after laparoscopic compared with open procedures. OBJECTIVE: To compare the
      incidence of VTE after laparoscopic and open surgery over a 5-year period.
      PATIENTS AND INTERVENTIONS: Clinical data of patients who underwent open or
      laparoscopic appendectomy, cholecystectomy, antireflux surgery, and gastric
      bypass between 2002 and 2006 were obtained from the University HealthSystem
      Consortium Clinical Database. The principal outcome measure was the incidence of
      venous thrombosis or pulmonary embolism occurring during the initial
      hospitalization after laparoscopic and open surgery. RESULTS: During the 60-month
      period, a total of 138,595 patients underwent 1 of the 4 selected procedures.
      Overall, the incidence of VTE was significantly higher in open cases (271 of
      46,105, 0.59%) compared with laparoscopic cases (259 of 92,490, 0.28%, P < 0.01).
      Our finding persists even when the groups were stratified according to level of
      severity of illness. The odds ratio (OR) for VTE in open procedures compared with
      laparoscopic procedures was 1.8 [95% confidence interval (CI) 1.3-2.5]. On subset
      analysis of individual procedures, patients with minor/moderate severity of
      illness level who underwent open cholecystectomy, antireflux surgery, and gastric
      bypass had a greater risk for developing perioperative VTE than patients who
      underwent laparoscopic cholecystectomy (OR: 2.0; 95% CI: 1.2-3.3; P < 0.01),
      antireflux surgery (OR: 24.7; 95% CI: 2.6-580.9; P < 0.01), and gastric bypass
      (OR: 3.4; 95% CI: 1.8-6.5; P < 0.01). CONCLUSIONS: Within the context of this
      large administrative clinical data set, the frequency of perioperative VTE is
      lower after laparoscopic compared with open surgery. The findings of this study
      can provide a basis to help surgeons estimate the risk of VTE and implement
      appropriate prophylaxis for patients undergoing laparoscopic surgical procedures.

PMID- 18043106
TI  - Substantial intentional weight loss and mortality in the severely obese.
AB  - OBJECTIVE: To compare all-cause mortality in a surgical weight loss cohort with a
      similarly aged, obese population-based cohort. SUMMARY BACKGROUND DATA:
      Significant weight loss following bariatric surgery improves the comorbidities
      associated with obesity. Improved survival as a result of surgical weight loss
      has yet to be clearly demonstrated using clinical data. METHODS: The surgical
      weight loss cohort was a series of consecutive patients treated with a
      laparoscopic adjustable gastric band in Melbourne between June 1994 and April
      2005. The Melbourne Collaborative Cohort Study (MCCS) provided a community
      control cohort, recruited between 1992 and 1994 and followed to June 2005 to
      determine vital status. Height and weight were recorded at baseline in both
      studies. Subjects between 37 and 70 years and with a body mass index (BMI) of >
      or =35 were included. Vital status was determined by follow-up and searching of
      death registries. Survival time was compared using Kaplan-Meier estimates, and
      hazard of death was determined using Cox regression, adjusting for sex, age at
      baseline, and BMI at baseline. RESULTS: Of 966 weight loss patients (mean age 47
      years, mean BMI 45 kg/m), the median follow-up time was 4 years. Mean weight loss
      after 2 years was 22.8% +/- 9% (58% of excess weight). The MCCS cohort included
      2119 severely obese members (mean age, 55 years; mean BMI, 38 kg/m; median follow
      up time, 12 years). There were 4 deaths in the weight loss cohort and 225 deaths
      in the MCCS cohort. Weight loss patients had 72% lower hazard of death than the
      community control cohort (hazard ratio, 0.28; 95% confidence interval, 0.10
      0.85). CONCLUSIONS: Substantial surgical weight loss in a morbidly obese
      population was associated with a significant survival advantage.

PMID- 18043107
TI  - Predictive factors of outcome after gastric banding: a nationwide survey on the
      role of center activity and patients' behavior.
AB  - BACKGROUND: Systematic studies of postoperative outcome of bariatric surgery
      provide information on the predictors of success. Surgeon's and institution
      experience and patient's behavior after surgery are key determinant of success or
      failure. Data on clinical trials generally reflect the experience of skilled
      obesity surgery centers. Little is known about the current practice at a
      nationwide level. The present study was realized in the frame of a national
      survey on medical and surgical practices conducted by the public health insurance
      system. The objective was to analyze systematically and prospectively the outcome
      of all bariatric surgery procedures consecutively performed in a given period, as
      registered by the French National Medical Insurance Service. This study at a
      nationwide level focused on predictive factors of success and analyzed how the
      experience of the centers relates to the patients' outcomes at 1 and 2 years
      after surgery. METHODS: This study examined prospectively the 2-year predictors
      of success of all consecutive 1236 bariatric operations performed at a nationwide
      level. Most (87.3%) were laparoscopic adjustable gastric banding (LAGB), so that
      the non-LAGB were eliminated from the study. Data were collected independently by
      consultants of the French National Medical Insurance Service: characteristics of
      the patients, evolution of body mass index (BMI), physical activity and
      comorbidities, changes in behavior, complications, reoperations. Information was
      available on the activity of the surgical teams. Excess weight loss (EWL) >50%
      was considered a "success," and EWL <50% "not a success." A backstep logistic
      regression (likelihood ratio test) was used to determine predictive factors.
      RESULTS: Statistical analysis showed significant differences in EWL with the
      following data: age <40 years (P < 0.01), initial BMI <50 kg/m (P < 0.001),
      experience of the surgeon(s) >2 procedures per week (P < 0.01), recovery of
      physical activity (P < 0.001), and change in eating habits (P < 0.001). Compared
      with 15- to 39-year-old patients, 40- to 49-year-old patients have a 1.5 higher
      risk not to have a success after surgery and over 50-year-old patients a 1.8
      higher risk. Morbidly obese patients (40 < BMI < 49) had a 2.6 times higher risk
      not to have a success than patients with severe obesity (35 < BMI < 39).
      Superobese patients (BMI >50) had a 5.4 times higher risk not to succeed than
      patients with severe obesity. Being operated by a team with a surgical activity
      over 15 bariatric procedures/2 months doubles the chance of a successful
      operation when compared with patients operated by surgical teams having only
      performed 1 or 2 bariatric procedures. Patients who had not recovered or
      increased their physical activity after operation had a 2.3 times higher risk not
      to have a success than those who did. Patients who had not changed their eating
      habits had a 2.2 times higher risk not to have a success than those who did.
      CONCLUSIONS: This nationwide survey shows that the best profile for a success
      after gastric banding is a patient <40 years, with an initial BMI <50 kg/m,
      willing to change his eating habits and to recover or increase his physical
      activity after surgery and who has been operated by a team usually performing >2
      bariatric procedures per week. This study emphasizes that obesity surgery
      requires a significant experience of the surgical team and a multidisciplinary
      approach to improve behavioral changes.

PMID- 18043108
TI  - Prognostic significance of multiple molecular markers for patients with stage II
      colorectal cancer undergoing curative resection.
AB  - OBJECTIVE: The aim of this study was to determine whether our constructed high
      sensitivity colorimetric membrane-array method could detect circulating tumor
      cells (CTCs) in the peripheral blood of stage II colorectal cancer (CRC) patients
      and so identify a subgroup of patients who are at high risk for relapse. SUMMARY
      BACKGROUND DATA: Adjuvant chemotherapy is not routinely recommended in patients
      diagnosed with UICC stage II CRC. However, up to 30% of patients with stage II
      disease relapse within 5 years of surgery from recurrent or metastatic disease.
      The identification of reliable prognostic factors for high-risk stage II CRC
      patients is imperative. METHODS: Membrane-arrays consisting of a panel of mRNA
      markers that included human telomerase reverse transcription (hTERT), cytokeratin
      19 (CK-19), cytokeratin-20 (CK-20), and carcinoembryonic antigen (CEA) mRNA were
      used to detect CTCs in the peripheral blood of 194 stage II CRC patients who
      underwent potentially curative (R0) resection between January 2002 and December
      2005. Digoxigenin (DIG)-labeled cDNA were amplified by RT-PCR from the peripheral
      blood samples, which were then hybridized to the membrane-array. All patients
      were followed up regularly, and their outcomes were investigated completely.
      RESULTS: Overall, 53 of 194 (27.3%) stage II patients were detected with the
      expression of all 4 mRNA markers using the membrane-array method. After a median
      follow up of 40 months, 56 of 194 (28.9%) developed recurrence/metastases
      postoperatively. Univariately, postoperative relapse was significantly correlated
      with the depth of invasion (P < 0.001), the presence of vascular invasion (P <
      0.001), the presence of perineural invasion (P = 0.048), the expression of all 4
      mRNA markers (P < 0.001), and the number of examined lymph nodes (P = 0.031).
      Meanwhile, using a multivariate logistic regression analysis, T4 depth of tumor
      invasion (P = 0.013), the presence of vascular invasion (P = 0.032), and the
      expression of all 4 mRNA markers (P < 0.001) were demonstrated to be independent
      predictors for postoperative relapse. Combination of the depth of tumor invasion,
      vascular invasion, and all 4 mRNA markers as predictors of postoperative relapse
      showed that patients with any 1 positive predictor had a hazard ratio of about 27
      fold to develop postoperative relapse (P < 0.001; 95% CI = 11.42-64.40). The
      interval between the detection of all 4 positive molecular markers and
      subsequently developed postoperative relapse ranged from 4 to 10 months (median:
      7 months). Furthermore, the expression of all 4 mRNA markers in all stage II CRC
      patients, or either stage II colon or rectal cancer patients were strongly
      correlated with poorer relapse-free survival rates by survival analyses (all P <
      0.001). CONCLUSIONS: The pilot study suggests that the constructed membrane-array
      method for the detection of CTCs is a potential auxiliary tool to conventional
      clinicopathological variables for the prediction of postoperative relapse in
      stage II CRC patients who have undergone curative resection.

PMID- 18043109
TI  - Inflammation-based prognostic score is a novel predictor of postoperative outcome
      in patients with colorectal cancer.
AB  - OBJECTIVE: To investigate the significance of preoperative Glasgow prognostic
      score (GPS) for postoperative prognostication of patients with colorectal cancer.
      BACKGROUND: Recent studies have revealed that the GPS, an inflammation-based
      prognostic score that includes only C-reactive protein (CRP) and albumin, is a
      useful tool for predicting postoperative outcome in cancer patients. However, few
      studies have investigated the GPS in the field of colorectal surgery. METHODS:
      The GPS was calculated on the basis of admission data as follows: patients with
      an elevated level of both CRP (>10 mg/L) and hypoalbuminemia (Alb <35 g/L) were
      allocated a score of 2, and patients showing 1 or none of these blood chemistry
      abnormalities were allocated a score of 1 or 0, respectively. Prognostic
      significance was analyzed by univariate and multivariate analyses. RESULTS: A
      total of 315 patients were evaluated. Kaplan-Meier analysis and log-rank test
      revealed that a higher GPS predicted a higher risk of postoperative mortality (P
      < 0.01). Univariate analyses revealed that postoperative TNM was the most
      sensitive predictor of postoperative mortality (odds ratio, 0.148; 95% confidence
      interval, 0.072-0.304; P < 0.0001). Multivariate analyses using factors such as
      age, sex, tumor site, serum carcinoembryonic antigen, CA19-9, CA72-4, CRP,
      albumin, and GPS revealed that GPS (odds ratio, 0.165; 95% confidence interval,
      0.037-0.732; P = 0.0177) was associated with postoperative mortality.
      CONCLUSIONS: Preoperative GPS is considered to be a useful predictor of
      postoperative mortality in patients with colorectal cancer.

PMID- 18043110
TI  - Surgical approach to bismuth Type I and II hilar cholangiocarcinomas: audit of 54
      consecutive cases.
AB  - OBJECTIVE: To clarify the optimal surgical strategy for Bismuth type I and II
      hilar cholangiocarcinomas. SUMMARY BACKGROUND DATA: Local or hilar resections is
      often performed for Bismuth type I and II tumors; however, reported outcomes have
      been unsatisfactory with a high recurrence and low survival rate. To improve
      survival, some authors have recommended right hepatectomy. However, the clinical
      value of this approach has not been validated. METHODS: Records of 54 consecutive
      patients who underwent resection of a Bismuth type I or II hilar
      cholangiocarcinoma were analyzed retrospectively. Through 1996, bile duct
      resection or the smallest necessary hepatic segmentectomy was performed.
      Beginning in 1997, choice of resection was based on the cholangiographic tumor
      type. For nodular or infiltrating tumor, right hepatectomy was indicated; for
      papillary tumor, bile duct resection with or without limited hepatectomy was
      chosen. RESULTS: Right hepatectomy was performed in 5 (20.8%) of 24 patients
      through 1996 and was done in 22 (73.3%) of 30 patients from 1997 (P = 0.0003). In
      patients without pM1 disease, R0 resection was achieved more frequently in the
      later period than in the earlier period (23 of 24 = 95.8% vs. 13 of 21 = 61.9%, P
      = 0.0073), which lead to better survival (5-year survival, 44.3% vs. 25.0%, P =
      0.0495). In the 31 patients with nodular or infiltrating tumor, who tolerated
      surgery and did not have pM1 disease, survival was better in the 18 patients who
      underwent right hepatectomy than in those who did not (5-year survival, 62.9% vs.
      23.1%, P = 0.0030). In cases of papillary tumor, bile duct resection with or
      without limited hepatectomy was sufficient to improve long-term survival.
      CONCLUSIONS: The surgical approach to Bismuth type I and II hilar
      cholangiocarcinomas should be determined according to cholangiographic tumor
      type. For nodular and infiltrating tumors, right hepatectomy is essential; for
      papillary tumor, bile duct resection with or without limited hepatectomy is
      adequate.

PMID- 18043111
TI  - Fatty pancreas: a factor in postoperative pancreatic fistula.
AB  - OBJECTIVE: To determine whether patients who develop a pancreatic fistula after
      pancreatoduodenectomy are more likely to have pancreatic fat than matched
      controls. BACKGROUND: Pancreatic fistula continues to be a major cause of
      postoperative morbidity and increased length of stay after pancreatoduodenectomy.
      Factors associated with postoperative pancreatic fistula include a soft pancreas,
      a small pancreatic duct, the underlying pancreatic pathology, the regional blood
      supply, and surgeon's experience. Fatty pancreas previously has not been
      considered as a contributing factor in the development of postoperative
      pancreatic fistula. METHODS: Forty patients with and without a pancreatic fistula
      were identified from an Indiana University database of over 1000 patients
      undergoing pancreatoduodenectomy and matched for multiple parameters including
      age, gender, pancreatic pathology, surgeon, and type of operation. Surgical
      pathology specimens from the pancreatic neck were reviewed blindly for fat,
      fibrosis, vessel density, and inflammation. These parameters were scored (0-4+).
      RESULTS: The pancreatic fistula patients were less likely (P < 0.05) to have
      diabetes but had significantly more intralobular (P < 0.001), interlobular (P <
      0.05), and total pancreatic fat (P < 0.001). Fistula patients were more likely to
      have high pancreatic fat scores (50% vs. 13%, P < 0.001). Pancreatic fibrosis,
      vessel density, and duct size were lower (P < 0.001) in the fistula patients and
      negative correlations (P < 0.001) existed between fat and fibrosis (R = -0.40)
      and blood vessel density (R = -0.15). CONCLUSIONS: These data suggest that
      patients with postoperative pancreatic fistula have (1) increased pancreatic fat
      and (2) decreased pancreatic fibrosis, blood vessel density, and duct size.
      Therefore, we conclude that fatty pancreas is a risk factor for postoperative
      pancreatic fistula.

PMID- 18043112
TI  - Right hepatic trisectionectomy for hepatobiliary diseases: results and an
      appraisal of its current role.
AB  - OBJECTIVE: To assess the results of 275 patients undergoing right hepatic
      trisectionectomy and to clarify its current role. SUMMARY BACKGROUND DATA: Right
      hepatic trisectionectomy is considered one of the most extensive liver
      resections, and few reports have described the long-term results of the
      procedure. METHODS: Short- and long-term outcomes of 275 consecutive patients who
      underwent right hepatic trisectionectomy from January 1993 to January 2006 were
      analyzed. RESULTS: Of the 275 patients, 160 had colorectal metastases, 49 had
      biliary tract cancers, 20 had hepatocellular carcinomas, 20 had other metastatic
      tumors, and 12 had benign diseases. Fourteen of the 275 patients underwent right
      hepatic trisectionectomy as part of auxiliary liver transplantation for acute
      liver failure and were excluded. Concomitant procedures were carried out in 192
      patients: caudate lobectomy in 45 patients, resection of tumors from the liver
      remnant in 57 patients, resection of the extrahepatic biliary tree in 45
      patients, and lymphadenectomy in 45 patients. One-, 3-, 5-, and 10-year survivals
      were 74%, 54%, 43%, and 36%, respectively. Overall hospital morbidity and 30-day
      and in-hospital mortalities were 41%, 7%, and 8%, respectively. Survivals for
      individual tumor types were acceptable, with 5-year survivals for colorectal
      metastasis and cholangiocarcinoma being 38% and 32%, respectively. Multivariate
      analysis disclosed the amount of intraoperative blood transfusion to be the sole
      independent predictor for the development of hospital morbidity. Age over 70
      years, preoperative bilirubin levels, and the development of postoperative renal
      failure were found to be independent predictors of long-term survival.
      CONCLUSION: Right hepatic trisectionectomy remains a challenging procedure. The
      outcome is not influenced by additional concomitant resection of tumors from the
      planned liver remnant. Caution must be taken when considering patients older than
      70 years for such resections.

PMID- 18043113
TI  - Is total parathyroidectomy the treatment of choice for hyperparathyroidism in
      multiple endocrine neoplasia type 1?
AB  - OBJECTIVE: The aim of the present report is to describe the results obtained with
      total parathyroidectomy (TPTX) guided by rapid intraoperative parathyroid hormone
      (PTH) evaluation, followed by immediate parathyroid autograft with fresh tissue.
      SUMMARY BACKGROUND DATA: Surgery for hyperparathyroidism (HPT) in multiple
      endocrine neoplasia type 1 (MEN1) is performed with various surgical approaches.
      METHODS: We report our 16-year experience of surgical treatment of 51 MEN1-HPT
      patients using TPTX and thymectomy. Forty-five patients underwent TPTX as the
      first surgical procedure, whereas for 6 patients, a parathyroid operation was the
      second surgical procedure. PTH intraoperative values less than 10 pg/mL, at the
      end of the surgery, were indicative for reimplantation of a few fragments (
      approximately 7) of fresh parathyroid tissue in the brachioradial muscle of the
      forearm. Parathyroid autograft was performed in all patients, except 3 in whom
      the fourth parathyroid gland was not found. RESULTS: Persistent
      hypoparathyroidism occurred in 13 patients (25%), with higher incidence in
      patients undergoing a second surgical revision for cervical recurrence than in
      patients submitted to the first surgery. At follow-up, 5 recurrences (
      approximately 10%) in the forearm were observed after a mean time of 7 +/- 5 (M
      +/- SD) years. No cervical recurrence was documented. The forearm recurrence was
      treated with removal of 1 or 2 enlarged fragments obtaining the resolution of HPT
      in all but 1 case. CONCLUSIONS: Based on the occurrence of complications in our
      experience, TPTX followed by autograft and guided by intraoperative PTH
      monitoring represents a better surgical option in MEN1-HPT compared with other
      surgical approaches.

PMID- 18043114
TI  - Racial disparities in clinical and economic outcomes from thyroidectomy.
AB  - CONTEXT: Thyroid disease is common, and thyroidectomy is a mainstay of treatment
      for many benign and malignant thyroid conditions. Overall, thyroidectomy is
      associated with favorable outcomes, particularly if experienced surgeons perform
      it. OBJECTIVE: To examine racial differences in clinical and economic outcomes of
      patients undergoing thyroidectomy in the United States. DESIGN, SETTING,
      PATIENTS: The nationwide inpatient sample was used to identify thyroidectomy
      admissions from 1999 to 2004, using ICD-9 procedure codes. Race and other
      clinical and demographic characteristics of patients were collected along with
      surgeon volume and hospital characteristics to predict outcomes. MAIN OUTCOME
      MEASURES: Inpatient mortality, complication rates, length of stay (LOS),
      discharge status, and mean total costs by racial group. RESULTS: In 2003-2004,
      16,878 patients underwent thyroid procedures; 71% were white, 14% black, 9%
      Hispanic, and 6% other. Mean LOS was longer for blacks (2.5 days) than for whites
      (1.8 days, P < 0.001); Hispanics had an intermediate LOS (2.2 days). Although
      rare, in-hospital mortality was higher for blacks (0.4%) compared with that for
      other races (0.1%, P < 0.001). Blacks trended toward higher overall complication
      rates (4.9%) compared with whites (3.8%) and Hispanics (3.6%, P = 0.056). Mean
      total costs were significantly lower for whites ($5447/patient) compared with
      those for blacks ($6587) and Hispanics ($6294). The majority of Hispanics (55%)
      and blacks (52%) had surgery by the lowest-volume surgeons (1-9 cases per year),
      compared with only 44% of whites. Highest-volume surgeons (>100 cases per year)
      performed 5% of thyroidectomies, but 90% of their patients were white (P <
      0.001). Racial disparities in outcomes persist after adjustment for surgeon
      volume group. CONCLUSIONS: These findings suggest that, although thyroidectomy is
      considered safe, significant racial disparities exist in clinical and economic
      outcomes. In part, inequalities result from racial differences in access to
      experienced surgeons; more data are needed with regard to racial differences in
      thyroid biology and surveillance to explain the balance of observed disparities.

PMID- 18043115
TI  - The optimal timing of intestinal transplantation for children with intestinal
      failure: a Markov analysis.
AB  - OBJECTIVE: Identify an optimal approach to the timing of intestinal
      transplantation for children dependent on total parenteral nutrition (PN).
      SUMMARY BACKGROUND DATA: Children with short bowel syndrome are frequently
      dependent on PN for growth and development. Intestinal transplantation is often
      considered after PN-related complications occur, but optimal timing of
      transplantation is controversial. METHODS: A Markov analytic model was used to
      determine life expectancy (LY) and quality-adjusted life years on a theoretical
      cohort of 4-year-old subjects for two treatment strategies: (1) standard care
      consisting of PN and referral to transplantation according to accepted guidelines
      and (2) early listing for isolated small intestine transplantation. RESULTS:
      Early listing for intestinal transplantation was associated with 0.27 additional
      life years (13.16 vs. 12.89) and 0.76 additional quality-adjusted life years
      (10.51 vs. 9.75) as compared with current standard care. The unadjusted analysis
      was sensitive to the development of PN-associated liver disease, at a threshold
      of approximately 11% per year, and its related probability of dying at a
      threshold of 80% 2-year mortality. Early listing for transplantation was the
      dominant strategy until the probability of late bowel rejection reached 35% per
      year. CONCLUSIONS: Children with short bowel syndrome dependent on PN should be
      considered for intestinal transplantation earlier than what is current practice.

PMID- 18043116
TI  - The Michigan surgical quality collaborative: will a statewide quality improvement
      initiative pay for itself?
AB  - OBJECTIVE: In this article, we detail a unique collaboration between hospitals in
      Michigan and a major third party payer, using a "pay for participation model."
      The payer has made a significant investment in this regional surgical quality
      improvement (QI) program and funds each center's participation. RESULTS: Based on
      the documented costs and incidence of surgical complications at our center, we
      estimate that a 1.8% annual reduction in complication rates is required for the
      payer to recoup its investment in this regional QI program. If we achieve our
      goal of a 3% reduction in complications per year over the 3-year program, the
      payer will save $2.5 million in payments. Our findings suggest that only a very
      modest improvement in surgical results, of a magnitude that seems realistically
      achievable based on similar QI initiatives, is necessary to financially justify
      payer involvement in a statewide quality improvement initiative. CONCLUSION: The
      framework of this program should be used by surgeons to attract private payers
      into QI collaboratives, facilitating improved patient outcomes and decreased
      health care expenditures.

PMID- 18043117
TI  - The quality of trials in operative surgery.
AB  - OBJECTIVE: This study aimed to assess the reported quality of trials in operative
      surgery. SUMMARY BACKGROUND DATA: Randomized controlled trials (RCTs) in
      operative surgery have previously been criticized for using weak methodology
      despite no evidence to suggest their quality is any different from nonsurgical
      trials. STUDY DESIGN: All surgical RCTs published in the British Medical Journal,
      the Journal of the American Medical Association, The Lancet, and the New England
      Journal of Medicine between 1998 and 2004 were identified. The adequacy of the
      reported methodology used to perform the randomization, power calculation, and
      recruitment was assessed for each trial using predefined criteria. The results
      from the surgical trials were compared with a randomly selected control group of
      nonsurgical RCTs, which were matched for journal and year of publication.
      RESULTS: Sixty-six surgical RCTs were identified. Adequate reporting of
      randomization sequence generation was seen in 42% (n = 28) of surgical trials and
      30% (n = 20) of nonsurgical trials, and adequate allocation concealment was
      recorded in 46% (n = 30) and 47% (n = 31), respectively. When combining these 2
      interrelated steps of randomization, only 26% (n = 17) of surgical trials and 23%
      (n = 15) of nonsurgical trials reported both adequately. Adequate recruitment was
      recorded in 52% (n = 33 of 63) surgical and 55% (n = 33 of 60) nonsurgical
      trials, with approximately a quarter (n = 17 and n = 16, respectively) of the
      trials in both the surgical and nonsurgical categories reporting an adequate
      power calculation. CONCLUSIONS: There was no evidence that the reported quality
      of surgical trials was different to nonsurgical trials. However, approximately
      half or less of all the trials reviewed reported adequate methodology.

PMID- 18043118
TI  - Little science, big science: strategies for research portfolio selection in
      academic surgery departments.
AB  - OBJECTIVE: To evaluate National Institutes of Health (NIH) funding for academic
      surgery departments and to determine whether optimal portfolio strategies exist
      to maximize this funding. SUMMARY BACKGROUND DATA: The NIH budget is expected to
      be relatively stable in the foreseeable future, with a modest 0.7% increase from
      2005 to 2006. Funding for basic and clinical science research in surgery is also
      not expected to increase. METHODS: NIH funding award data for US surgery
      departments from 2002 to 2004 was collected using publicly available data
      abstracted from the NIH Information for Management, Planning, Analysis, and
      Coordination (IMPAC) II database. Additional information was collected from the
      Computer Retrieval of Information on Scientific Projects (CRISP) database
      regarding research area (basic vs. clinical, animal vs. human, classification of
      clinical and basic sciences). The primary outcome measures were total NIH award
      amount, number of awards, and type of grant. Statistical analysis was based on
      binomial proportional tests and multiple linear regression models. RESULTS: The
      smallest total NIH funding award in 2004 to an individual surgery department was
      a single $26,970 grant, whereas the largest was more than $35 million comprising
      68 grants. From 2002 to 2004, one department experienced a 336% increase
      (greatest increase) in funding, whereas another experienced a 73% decrease
      (greatest decrease). No statistically significant differences were found between
      departments with decreasing or increasing funding and the subspecialty of basic
      science or clinical research funded. Departments (n = 5) experiencing the most
      drastic decrease (total dollars) in funding had a significantly higher proportion
      of type K (P = 0.03) grants compared with departments (n = 5) with the largest
      increases in total funding; the latter group had a significantly increased
      proportion of type U grants (P = 0.01). A linear association between amount of
      decrease/increase was found with the average amount of funding per grant and per
      investigator (P < 0.01), suggesting that departments that increased their total
      funding relied on investigators with large amounts of funding per grant.
      CONCLUSIONS: Although incentives to junior investigators and clinicians with
      secondary participation in research are important, our findings suggest that the
      best strategy for increasing NIH funding for surgery departments is to invest in
      individuals with focused research commitments and established track records of
      garnering large and multiple research grants.

PMID- 18043119
TI  - Does a biologic prosthesis really reduce recurrence after laparoscopic
      paraesophageal hernia repair?

PMID- 18043120
TI  - Prophylactic ilioinguinal neurectomy in open inguinal hernia repair: a double
      blind randomized controlled trial.

PMID- 18043123
TI  - Mental training in surgical education.

PMID- 18043124
TI  - Single-agent treatment with pegylated liposomal doxorubicin for metastatic breast
      cancer.
AB  - Anthracyclines and taxanes are among the most active substances used in the
      treatment of metastatic breast cancer (MBC). Their frequent use in the adjuvant
      setting and in cumulative toxicities including cardiotoxicity, however, often
      limit their use in MBC. The trend towards the use of adjuvant trastuzumab
      containing regimens, which can also produce cardiotoxicity, adds further support
      to the need for effective agents with improved tolerability in the metastatic
      setting. Pegylated liposomal doxorubicin (PLD) can be an effective alternative to
      conventional anthracyclines for certain women with MBC. In phase III clinical
      trials, PLD was as effective as doxorubicin and produced significantly less
      cardiotoxicity in women with MBC. The incidences of myelotoxicity,
      nausea/vomiting, and alopecia were also lower with PLD, whereas hand-foot
      syndrome and stomatitis occurred more frequently. Phase II and III trials
      conducted in women with MBC support the use of PLD monotherapy in patients
      relapsing after adjuvant anthracycline-containing therapy, in heavily pretreated
      patients with taxane-refractory disease, in patients with cardiovascular risk
      factors (e.g. hypertension and mediastinal irradiation), in elderly patients, and
      in patients for whom specific acute doxorubicin toxicities, such as alopecia, are
      particularly worrying.

PMID- 18043125
TI  - SCH66336, inhibitor of protein farnesylation, blocks signal transducer and
      activators of transcription 3 signaling in lung cancer and interacts with a small
      molecule inhibitor of epidermal growth factor receptor/human epidermal growth
      factor receptor 2.
AB  - Signal transducer and activators of transcription 3 (STAT3) is an important
      transcription factor that is essential for lung cancer cell survival. STAT3 is
      activated by diverse upstream receptor and nonreceptor tyrosine kinases, and
      blockade of STAT3 results in tumor growth inhibition. Therefore, a search for
      STAT3 inhibitors is under way. We demonstrate that SCH66336, at 4 mumol/l,
      completely blocks STAT3 phosphorlyation in a variety of nonsmall cell lung
      carcinoma (NSCLC) cell lines, whereas the effect on AKT and extracellular signal
      regulated kinase activation is variable. Furthermore, SCH66336 has
      antiproliferative effects on NSCLC cells. When NSCLC cells are exposed
      sequentially to SCH66336 and a small molecule dual tyrosine kinase inhibitor of
      epidermal growth factor receptor and human epidermal growth factor receptor 2,
      synergistic activity is observed with an increase in the fraction of cells
      undergoing apoptosis. Concurrent exposure to both agents is, however, associated
      with antagonism and decreased apoptosis. We conclude that blockade of STAT3
      phosphorylation might be one of the mechanisms by which SCH66336 exerts its
      antitumor activity, and that this can be synergistic in vitro when administered
      sequentially with epidermal growth factor receptor inhibitors.

PMID- 18043126
TI  - Alterations in vascular architecture and permeability following OXi4503
      treatment.
AB  - OXi4503 retards tumor growth in a dose-dependent manner and improves survival in
      a murine model of colorectal liver metastases. This agent causes extensive
      vascular shutdown by selectively altering the tubulin cytoskeleton within the
      endothelial cells of tumor vessels. The destruction of tumor vessels is
      incomplete, however, and tumor revascularization occurs after the treatment. This
      study evaluates the pattern of microcirculatory changes and alterations to the
      ultrastructural properties of the tumor vasculature that result from OXi4503
      treatment. Male CBA mice were induced with liver metastases via an intrasplenic
      injection of a murine-derived colorectal cell line. After administering a single
      intraperitoneal dose of OXi4503, changes in tumor perfusion, microvascular
      architecture and permeability were assessed at various time points. One hour
      after a 100-mg/kg dose of OXi4503, a significant decrease in the percentage of
      tumor perfusion (63.96+/-1.98 in controls versus 43.77+/-2.71 in treated mice,
      P<0.001) was observed, which was still evident 5 days after the treatment.
      Substantial tumor microvascular damage and minimal normal liver injury were
      observed. Tumor vascular permeability was significantly elevated 45 min after the
      OXi4503 treatment (67.5+/-3.60 in controls versus 80.5+/-2.24 microg/g, P<0.05).
      The findings suggest that OXi4503 selectively targets tumor vessels and causes
      immediate microvascular destruction. Even at the maximum tolerated dose, however,
      residual patent tumor vessels were still present after treatment, implying
      incomplete tumor destruction. A combination of OXi4503 with other
      chemotherapeutic modalities might achieve complete tumor eradication and improve
      long-term survival.

PMID- 18043127
TI  - Synthesis and anticancer activities of 6-amino amonafide derivatives.
AB  - Amonafide is a DNA intercalator and topoisomerase II inhibitor in clinical
      development for the treatment of neoplastic diseases. Amonafide contains a free
      arylamine, which causes it to be metabolized in humans by N-acetyl transferase-2
      (NAT2) into a toxic form. To eliminate the NAT2 acetylation of amonafide while
      retaining the anticancer properties, we have synthesized nine derivatives that
      are structurally similar to amonafide that should not be acetylated. Eight
      derivatives have arylamines at the 6-position (vs. 5-position of amonafide) and
      one derivative completely lacks the arylamine. The derivative with a free amine
      in the 6-position and one with a substituted amine in the 6-position are not
      acetylated, whereas amonafide is extensively acetylated as determined by an NAT2
      assay. The biological activities of these compounds were evaluated to determine
      whether they behaved similarly to amonafide in purified systems and in vitro. We
      found that three compounds had similar cancer cell-selective growth inhibition to
      amonafide, while retaining similar subcellular localization, DNA intercalation
      and topoisomerase II inhibition activities. In addition, these compounds were
      able to eliminate a marker of metastatic potential, the perinucleolar
      compartment. These three compounds (named numonafides) might thus allow for
      better patient management than those treated with amonafide; hence, they should
      be developed further as potential clinical replacements for amonafide or as novel
      anticancer drugs.

PMID- 18043128
TI  - Exposure-response relationships for oxaliplatin-treated colon cancer cells.
AB  - Data are lacking for an optimal infusion length for oxaliplatin administered
      intraperitoneally. Our objectives were to establish the roles of hyperthermia and
      an effective length of oxaliplatin treatment in maximizing antitumor activity.
      SW620 cells were treated for 0.5 vs. 2 h and at 37 vs. 42 degrees C.
      Cytotoxicity, cell cycle analysis, subG1 and survival were assessed with the MTT
      assay, flow cytometry and the clonogenic assay. The IC50 for cells treated at 37
      degrees C was 2.90+/-0.83 microg/ml and at 42 degrees C, 1.99+/-0.66 microg/ml
      (P=0.14). The Emax for 37 degrees C was 93.9+/-2.57% and for 42 degrees C, 97.8+/
      1.59% (P=0.05). The subG1 fraction did not differ between cells treated at 37 and
      42 degrees C (P=0.12). The IC50 for the cells treated for 0.5 h was 10.6+/-0.60
      microg/ml and for 2 h, 2.80+/-1.70 microg/ml (P=0.02). The Emax for 0.5 h was
      87.9+/-5.13% and for 2 h, 96.6+/-3.35% (P=0.09). SubG1 for 0.5 h was 8.24+/-1.33%
      and for 2 h, 15.8+/-2.45% (P=0.02). Clonogenic assays demonstrated diminished
      survival when treated with low concentrations (10 microg/ml) of oxaliplatin
      combined with heat treatment (P=0.017) for 2 h, but not 0.5 h. Similar clonogenic
      assay experiments were performed with the oxaliplatin-resistant WiDr cell line,
      and differences in survival following oxaliplatin and heat treatment were again
      observed for 2 h, but not for 0.5 h (P=0.002). Drug treatment for 2 h of both
      SW620 and WiDr cell lines is superior to treatment for 0.5 h. Cell kill effects
      are reliant on treatment length; hence, the choice of time exposure must be made
      with a view to maintaining a balance between the cell kill effects and the
      clinical feasibility of treating the patient.

PMID- 18043129
TI  - Addition of PTK787/ZK 222584 can lower the dosage of amsacrine to achieve equal
      amounts of acute myeloid leukemia cell death.
AB  - Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been
      demonstrated that AML cells express the vascular endothelial growth factors,
      VEGFA and VEGFC, as well as kinase insert domain-containing receptor (VEGFR2),
      the main receptor for downstream effects, resulting in an autocrine pathway for
      cell survival. This study investigates the role of the VEGFR inhibitor PTK787/ZK
      222584 in leukemic cell death, and the possibility of an additional effect on
      cell death by a chemotherapeutic drug, amsacrine. In three AML cell lines and 33
      pediatric AML patient samples, we performed total cell-kill assays to determine
      the percentages of cell death achieved by PTK787/ZK 222584 and/or amsacrine. Both
      drugs induced AML cell death. Using a response surface analysis, we could show
      that, in cell lines as well as in primary AML blasts, an equal magnitude of
      leukemic cell death could be obtained when lower doses of the more toxic
      amsacrine were combined with low dosages of the less toxic VEGFR inhibitor. This
      study shows that PTK787/ZK 222584 might have more clinical potential in AML when
      combined with a chemotherapeutic drug such as amsacrine. In future, it will be
      interesting to study whether the complications and the long-term effects of
      chemotherapy can be reduced by lowering the dosages of amsacrine, and by
      replacing it with other drugs with lower toxicity profiles, such as PTK787/ZK
      222584.

PMID- 18043130
TI  - Norcantharidin induces anoikis through Jun-N-terminal kinase activation in CT26
      colorectal cancer cells.
AB  - Norcantharidin (NCTD), a chemically modified form of cantharidin, is a potential
      anticancer drug. This study investigated the effect of NCTD on anoikis in CT26
      colorectal adenocarcinoma cells. NCTD treatment of CT26 cells showed a dose
      dependent and time-dependent decrease in viability and cell proliferation. Growth
      inhibition was accompanied by cell cycle arrest in the S and G2/M phases. Mitogen
      activated protein kinase expression, assayed by Western blot, was unchanged
      except for Jun-N-terminal kinase (JNK). At 24 h of treatment with 0-20 micromol/l
      NCTD, JNK expression increased at 24 h, but then decreased at 48 h; in contrast,
      the phosphorylated JNK levels markedly increased. JNK inhibitor (SP600125) in the
      culture effectively blocked NCTD-induced cytotoxicity and detachment of cells.
      CT26 cells treated with NCTD not only displayed inhibited cell adhesion and down
      expression of integrin beta1, but also changed from being shuttle-shaped to
      round, the latter cells being more susceptible to anoikis-mediated apoptosis.
      Flow cytometric assay of the DNA content in NCTD-treated CT26 cells at 24 and 48
      h showed a marked increase in the sub-G1 level, indicating that NCTD induced
      apoptosis. NCTD inhibited the viability of CT26 cancer cells preferentially over
      normal bone marrow and mononuclear cells. NCTD inhibits CT26 cancer cells by
      blocking proliferation and inducing anoikis-mediated apoptosis, a process that
      might be regulated by JNK activation.

PMID- 18043131
TI  - Alkylphospholipids inhibit capillary-like endothelial tube formation in vitro:
      antiangiogenic properties of a new class of antitumor agents.
AB  - Synthetic alkylphospholipids (APLs), such as edelfosine, miltefosine and
      perifosine, constitute a new class of antineoplastic compounds with various
      clinical applications. Here we have evaluated the antiangiogenic properties of
      APLs. The sensitivity of three types of vascular endothelial cells (ECs) (bovine
      aortic ECs, human umbilical vein ECs and human microvascular ECs) to APL-induced
      apoptosis was dependent on the proliferative status of these cells and correlated
      with the cellular drug incorporation. Although confluent, nondividing ECs failed
      to undergo apoptosis, proliferating ECs showed a 3-4-fold higher uptake and
      significant levels of apoptosis after APL treatment. These findings raised the
      question of whether APLs interfere with new blood vessel formation. To test the
      antiangiogenic properties in vitro, we studied the effect of APLs using two
      different experimental models. The first one tested the ability of human
      microvascular ECs to invade a three-dimensional human fibrin matrix and form
      capillary-like tubular networks. In the second model, bovine aortic ECs were
      grown in a collagen gel sandwich to allow tube formation. We found that all three
      APLs interfered with endothelial tube formation in a dose-dependent manner, with
      a more than 50% reduction at 25 micromol/l. Interference with the angiogenic
      process represents a novel mode of action of APLs and might significantly
      contribute to the antitumor effect of these compounds.

PMID- 18043132
TI  - A phase I safety, tolerability, and pharmacokinetic study of enzastaurin combined
      with capecitabine in patients with advanced solid tumors.
AB  - Enzastaurin, an oral inhibitor of protein kinase Cbeta, affects signal
      transduction associated with angiogenesis, proliferation, and survival.
      Capecitabine is converted to 5-fluoruracil by thymidine phosphorylase, a putative
      angiogenic factor. The all-oral combination of the two drugs offers the potential
      for targeting angiogenesis in capecitabine-sensitive tumors with nonoverlapping
      toxicities. Patients with advanced cancer initially received single-agent
      enzastaurin to achieve steady-state concentrations (cycle 1). In subsequent 21
      day cycles, enzastaurin was given orally, once daily, on days 1-21 and
      capecitabine orally, twice daily (b.i.d.), on days 1-14 in three dose-level
      cohorts. Three dose-escalation cohorts were studied: cohort 1 (n=8), 350 mg of
      enzastaurin +capecitabine (750 mg/m2 b.i.d.); cohort 2 (n=7), enzastaurin (350
      mg)+capecitabine (1000 mg/m2 b.i.d.); cohort 3 (n=12), 525-mg capsules or 500-mg
      enzastaurin+capecitabine (1000 mg/m2 b.i.d.). Further dose escalation was not
      pursued because of emerging data that enzastaurin systemic exposure did not
      increase at doses above 525 mg. Although a traditional toxicity-based maximum
      tolerated dose was not achieved, the highest dosing cohort represented a
      biologically relevant dose of enzastaurin, on the basis of preclinical data and
      correlative pharmacodynamic biomarker assays of protein kinase Cbeta inhibition
      in peripheral blood mononucleocytes, in combination with a standard dose of
      capecitabine. For the 500/525-mg dose, ratios of total enzastaurin analyte
      geometric means (i.e. enzastaurin alone versus enzastaurin with capecitabine)
      reflected a trend toward decreased enzastaurin exposure, but did not reach
      statistical significance. The pharmacokinetic parameters of capecitabine with
      enzastaurin were similar to those previously reported for single-agent
      capecitabine. The regimen was well tolerated, without any consistent pattern of
      drug-related grade 3 or grade 4 toxicities being observed. Although no objective
      tumor responses were documented, five patients maintained stable disease for
      >or=6 months (range: 6-9.7 months). The recommended phase II dose of this
      combination, based on the results of this study, is enzastaurin at a daily dose
      of 500 mg (tablet formulation) and capecitabine (1000 mg/m2, b.i.d.) on days 1-14
      every 21 days. Further disease-directed studies are warranted, such as in
      malignancies in the treatment of which both capecitabine and inhibitors of
      angiogenesis have previously been benchmarked as being effective.

PMID- 18043133
TI  - Multi-institutional phase II trial of S-1 in patients with oral squamous cell
      carcinoma.
AB  - The aim of this study was to investigate the efficacy and safety of an oral
      fluoropyrimidine anticancer agent, S-1, in patients with oral squamous cell
      carcinoma. Patients with pathologically confirmed squamous cell carcinoma and at
      least one measurable lesion were enrolled. Oral administration of S-1 (40 mg/m2
      twice daily) for 28 days was followed by a 14-day rest period. A total of 41
      consecutive eligible patients were enrolled in the study between October 2002 and
      August 2004. The sites of the primary tumor were the gingiva (n=18), the tongue
      (n=12), the palate (n=5), the oral floor (n=4), the buccal mucosa (n=1), and the
      labial mucosa (n=1). A median of two cycles of treatment (range, 1-5) was
      administered. A complete response was achieved in nine patients and a partial
      response in eight patients, for an overall response rate of 41.5% (95% confidence
      interval, 26.4-56.5%). The 3-year survival rate was 76.4% (95% confidence
      interval, 62.8-90.0%). Although grade 3 anemia and anorexia occurred in two
      patients each (4.9%), and grade 3 neutropenia, thrombocytopenia, nausea,
      vomiting, stomatitis, and diarrhea in one patient each (2.4%), no grade 4
      toxicities were observed. S-1 exhibits definite antitumor activity in patients
      with oral squamous cell carcinoma and is well tolerated.

PMID- 18043134
TI  - Continuous oral capecitabine at fixed dose in patients older than 75 years with
      metastatic colorectal and gastric cancer: a study of the Multidisciplinary
      Oncology Group on Gastrointestinal Tumors.
AB  - The aim of this study was to investigate the safety profile of continuous oral
      capecitabine at fixed dose in patients older than 75 years, having metastatic
      colorectal and gastric cancer. Capecitabine was administered at a fixed dose of
      2000 mg daily without interruptions. Thirty-four patients were considered
      evaluable for toxicity and efficacy. The median age was 81 years (range 76-85).
      The median duration of treatment was 113 days (range 24-238 days). No grade 4
      toxicity was observed. One patient had grade 3 nausea and vomiting, and one had
      grade 3 diarrhea. Partial responses were observed in six patients with colorectal
      cancer, and in one patient with gastric cancer. This study suggests that
      continuous oral capecitabine at a fixed daily dose of 2000 mg is well tolerated,
      and that it allows for the simplification and ease of dosing in elderly patients
      with metastatic colorectal and gastric cancer.

PMID- 18043135
TI  - Cerebrovascular accident during cisplatin-based combination chemotherapy of
      testicular germ cell tumor: an unusual case report.
AB  - Even though testicular nonseminomatous germ cell tumors (NSGCTs) usually have a
      good prognosis and high curability rates, unpredicted complications owing to
      chemotherapy regimens might complicate the course. Modalities that are commonly
      used to cure NSGCTs have well-known side effects. Thromboembolism, which is
      infrequently associated with germ cell tumors and the vascular toxicity of
      chemotherapeutics, causes morbidity and mortality. We report a young testicular
      NSGCT patient, without any known underlying risk factor, who experienced an
      unpredicted cerebrovascular accident after he received cisplatin-based
      combination chemotherapy.

PMID- 18043136
TI  - Implantation of a Berlin Heart as single ventricle by-pass on Fontan circulation
      in univentricular heart failure.
AB  - The clinical management of ventricular failure after the Fontan operation
      presents a formidable challenge to surgeons. We report our experience with
      successful implantation of a Berlin Heart EXCOR ventricular assist device as a
      bridge to transplantation in a child with Fontan circulation.

PMID- 18043137
TI  - Heart transplantation after Fontan procedure in adults.
AB  - Complex congenital heart disease is the cause for 1.5%-2.4% of heart
      transplantations in adults. Indications for heart transplantation are ventricular
      dysfunction, failed Fontan physiology, and cyanosis. We present a 43-year-old
      man, 20 years after a Fontan operation by an univentricular heart, with a
      tricuspid atresia, L-Transposition of the Great Arteries, and high-grade
      subpulmonary stenosis. Persistent bleeding after successful transplantation
      necessitated major blood transfusions and reoperation. We reconstructed superior
      vena cava and vena brachiocephalica using a pericardial patch, and because of
      postoperative low output syndrome, he was connected to extracorporeal circulation
      through cannulation of femoral artery and explanted after hemodynamic stability.
      Heart transplantation can be successful in patients with end-stage congenital
      heart diseases after Fontan procedure, because of improved surgical and medical
      management. Challenges include limited ability to assess hemodynamics, complex
      anatomy, increased risk of bleeding caused by multiple prior procedures, and
      unique underlying pathologic states. Careful patient selection and surgical
      timing are essential to increase long-term survival.

PMID- 18043138
TI  - Surgical repair of congenital supravalvular aortic stenosis in adult.
AB  - Supravalvular aortic stenosis is a rare congenital cardiac anomaly occurring
      mainly as a part of Williams-Beuren syndrome. Aortic narrowing above the level of
      the aortic valve causes obstruction of the left ventricular outflow tract, and a
      pressure gradient between the left ventricle and the aorta causes left ventricle
      hypertrophy. We report here a case of a 22-year-old man who underwent extended
      patch aortoplasty because of supravalvular aortic stenosis accompanying Williams
      Beuren syndrome. He was in New York Heart Association functional class III with
      localized hourglass type supravalvular aortic stenosis. Related to arterial
      hypertension he was in a cardiac decompensation. Mean pressure gradient was 73 mm
      Hg and maximum gradient 104 mm Hg. Electrocardiography indicated left ventricle
      hypertrophy, which was also seen in x-ray, as heart enlargement. We successfully
      treated this patient with extended patch aortoplasty and immediate postoperative
      echocardiography showed reduction of gradient. Good surgical outcome of
      congenital supravalvular aortic stenosis in adults can be achieved with this
      treatment. This technique provides symmetric reconstruction of the aorta with
      good postoperative results and no gradient across aortic valve and aortic valve
      insufficiency remains, providing excellent long-term relief of localized
      supravalvular gradients and preservation of aortic valve competence.

PMID- 18043139
TI  - Benefits of pulsatile perfusion on vital organ recovery during and after
      pediatric open heart surgery.
AB  - Controversy continues concerning the utilization of pulsatile flow during
      cardiopulmonary bypass (CPB) procedures with regard to improved patient outcomes.
      We evaluated 215 consecutive pediatric patients undergoing open heart surgery for
      repair of congenital heart disease who were prospectively entered into the study
      and randomly assigned to either the pulsatile perfusion group (group P, n = 151)
      or the nonpulsatile perfusion group (group NP, n = 64). All patients received
      identical surgical, perfusional, and postoperative care. Major complications and
      clinical outcome were documented. There were no statistically significant
      differences seen in either preoperative or operative parameters between the two
      groups (age, body surface area, weight, X-clamp and CPB time, base flow, flow
      rates, and hemofiltration). Group P, compared with group NP, had significantly
      less inotropic support (number of agents 1.4 +/- 0.07 vs. 2 +/- 0.12, p = 0.0012;
      dopamine 7.14 +/- 0.28 vs. 9.04 +/- 0.42 microg 32 x kg x min, p = 0.00025;
      dobutamine 4.12 +/- 0.3 vs. 5.3 +/- 0.6 microg 32 x kg x min, p = 0.036),
      adrenalin (0.026 +/- 0.005 vs. 0.046 +/- 0.005 microg 32 x kg x min, p = 0.021),
      shorter intubation period (10.26 +/- 1.04 vs. 18.64 +/- 1.99 hours, p = 0.021),
      shorter duration of intensive care unit (ICU) (1.53 +/- 0.07 vs. 2.75 +/- 1.19
      days, p = 0.012), and hospital stay (6.71 +/- 0.19 vs. 11.16 +/- 0.58 days, p =
      0.002). Although there were no significant differences in either creatinine,
      enzyme levels, and drainage amounts between two groups, lower lactate levels
      16.27 +/- 2.02 vs. 24.66 +/- 3.05 mg/dl, p = 0.00034), higher albumine levels
      (3.15 +/- 0.03 vs. 2.95 +/- 0.06 mg/dl, p = 0.046), and higher urine output
      (602.82 +/- 21.5 vs. 505.55 +/- 34.2 ml/d, p = 0.016) during ICU period was
      observed in group P compared with group NP, respectively. We concluded that the
      use of pulsatile flow resulted in improved patient outcomes in terms of
      preserving better cardiac, renal, and pulmonary functions in the early post-CPB
      period.

PMID- 18043140
TI  - Technique for the Norwood procedure using normothermic selective cerebral
      perfusion.
AB  - The Norwood procedure is commonly performed using either circulatory arrest or
      deep hypothermia with low-flow cardiopulmonary bypass. We describe our technique
      for the Norwood procedure using selective cerebral perfusion with corporeal
      normothermia (> 32 degrees C). A right radial artery catheter was placed and
      cerebral NIRS applied. A C-clamp was placed upon the innominate artery and gortex
      shunt placed. Cardiopulmonary bypass was established through the shunt. A 7.0
      purse-string was placed at the beginning of the arch and a cross-clamp applied
      superior to this and cold cardioplegia was given by hand. The left carotid and
      subclavian were snared and a C-clamp was placed on the distal descending aorta.
      The cross-clamp was then repositioned across the base of the innominate and pump
      flow was reduced. This resulted in arch isolation with a bloodless field.
      Perfusion was then transferred to a neo-artic cannula and the central shunt
      completed. Cardiopulmonary bypass time was approximately 60 minutes and cardiac
      arrest time was approximately 20 minutes; core temperature had not dropped below
      32 degrees C. The Norwood procedure can be successfully performed with
      normothermic selective cerebral perfusion thereby offering the theoretical
      benefit of avoiding deep hypothermia with or without circulatory arrest.

PMID- 18043141
TI  - Usefulness of low prime perfusion pediatric circuit in decreasing blood
      transfusion.
AB  - We tested the efficiency of small prime volume in decreasing the blood
      requirement during pediatric cardiac surgery. This is a retrospective analysis of
      transfusion in 259 consecutive patients weighing <15 kg. We downsized the bypass
      circuit and avoided noncritical components to obtain a cardiopulmonary bypass
      prime volume, including a cardioplegia circuit of 140 ml for patients up to 6 kg,
      and of 170 ml for those weighing 6-15 kg. For intra- and postoperative care,
      transfusions were limited to 1 unit of packed red blood cells and 1 unit of fresh
      frozen plasma in 129 of the 134 patients weighing <6 kg. Seventy-six of 125 (61%)
      patients who were between 6 kg and 15 kg had bloodless surgery. None of the 259
      patients had platelets infusion. In transfused cases, only eight patients (3%)
      needed more than two different donor products. In bloodless cases, hemoglobin
      values were 11.5 +/- 1.8 g/dl before, 9.4 +/- 1.7 g/dl during, and 10.5 +/- 1.8
      g/dl after surgery. No adverse effects of this procedure were encountered. Small
      prime volume is efficient and safe in decreasing blood use in pediatric surgery.

PMID- 18043142
TI  - Impact of miniaturization of cardiopulmonary bypass circuit on blood transfusion
      requirement in neonatal open-heart surgery.
AB  - This study was undertaken to determine the impact of miniaturization of a
      cardiopulmonary bypass (CPB) circuit on blood transfusion and hemodynamics in
      neonatal open-heart surgery. Neonates (n = 102) undergoing open-heart surgery
      between 2002 and 2006 were included and divided into three groups: group 1 (n =
      28), Dideco 902 oxygenator + 5/16" line; group 2 (n = 29), Dideco 901 oxygenator
      + 1/4" line; group3 (n = 45), Dideco 901 oxygenator + 3/16" arterial + 1/4"
      venous line. Amount of priming volume, blood and bicarbonate sodium use during
      CPB, and hemodynamics were compared. Priming volume in the groups 2 and 3 was
      significantly less compared with the group 1 (group 1, 575 +/- 37 ml; group 2,
      328 +/- 12 ml, group 3, 326 +/- 5 ml, p < 0.05). Blood transfusion and
      bicarbonate sodium use during CPB in groups 2 and 3 were significantly less
      compared with group 1. Hemodynamics during CPB was comparable. There were no
      differences between groups 2 and 3 in any parameter. Miniaturization of the CPB
      circuit resulted in decrease in priming volume and subsequent reduction in blood
      and bicarbonate sodium use. Downsizing the lines had minimal impact on any of the
      parameters studied, and further efforts should be made to achieve neonatal open
      heart surgery without blood transfusion.

PMID- 18043143
TI  - Application of modified perfusion technique on one stage repair of interrupted
      aortic arch in infants: a case series and literature review.
AB  - One stage repair of interrupted aortic arch (IAA) associated with cardiac
      anomalies in neonates and infants is challenging for the entire surgical team.
      Deep hypothermic circulatory arrest (DHCA) prolongs myocardial and cerebral
      ischemia and may induce heart, brain, and major organ dysfunction. From May 2004
      to May 2006, 13 infants with IAA underwent one stage repair by median sternotomy
      under DHCA with continuous regional cerebral perfusion (RCP) in Fuwai Children's
      Heart Center. Median age at operation was 10.4 +/- 6.7 months, and mean body
      weight was 6.58 +/- 2.15 kg. Temperature of nasopharynx was decreased to 18
      degrees C-20 degrees C; rectal temperature was controlled at 19 degrees C-22
      degrees C. Flow rate of RCP was maintained with 20-25 ml x kg x min under DHCA
      combined with RCP. Mean artery pressure (MAP) measuring from right radial artery
      was 32.5 +/- 5.8 mm Hg, and MAP from femoral artery was 11.2 +/- 3.5 mm Hg. Mean
      cardiopulmonary bypass (CPB) time was 141.6 +/- 21.7 min, and mean aortic clamp
      time was 52.3 +/- 10.9 min. Mean duration of RCP was 31.5 +/- 12.4 min. Mean
      intubation time in intensive care unit (ICU) was 54.7 +/- 12.6 hours, and mean
      ICU stay was 67.9 +/- 28.4 hours. This report describes our CPB protocol under
      DHCA using continuous RCP in low weight pediatric patients to minimize
      neurological complications during one stage IAA repair and summarizes the various
      CPB managements in recent literature as well.

PMID- 18043144
TI  - The effect of temperature correction of blood gas values on the accuracy of end
      tidal carbon dioxide monitoring in children after cardiac surgery.
AB  - We evaluated accuracy of end-tidal carbon dioxide tension (PETco2) monitoring and
      measured the effect of temperature correction of blood gas values in children
      after cardiac surgery. Data from 49 consecutive mechanically ventilated children
      after cardiac surgery in the cardiac intensive care unit were prospectively
      collected. One patient was excluded from the study. Four arterial-end-tidal CO2
      pairs in each patient were obtained. Both the arterial carbon dioxide tension
      (Paco2) values determined at a temperature of 37 degrees C and values corrected
      to body temperature (Patcco2) were compared with the PETco2 values. After the
      surgical correction 28 patients had biventricular, acyanotic (mean age 2.7 +/-
      4.8 years) and 20 patients had a cyanotic lesion (mean age 1.0 +/- 1.7 years).
      The body temperature ranged from 35.2 degrees C to 38.9 degrees C. The Pa-PETco2
      discrepancy was affected both by the type of cardiac lesion and by the
      temperature correction of Paco2 values. Correlation slopes of the Pa-PETco2 and
      Patc-PETco2 discrepancies were significantly different (p = 0.040) when the body
      temperature was higher or lower than 37 degrees C. In children, after cardiac
      surgery, end-tidal CO2 monitoring provided a clinically acceptable estimate of
      arterial CO2 value, which remained stabile in repeated measurements. End-tidal
      CO2 monitoring more accurately reflects temperature-corrected blood gas values.

PMID- 18043145
TI  - Efficacy of a miniature centrifugal rotary pump (TinyPump) for transfusion-free
      cardiopulmonary bypass in neonatal piglets.
AB  - We have developed a miniaturized semiclosed cardiopulmonary bypass (CPB) circuit
      incorporating a centrifugal blood pump (TinyPump) with a volume of 5 ml. The
      current study was undertaken to evaluate the hemolytic performance of the
      TinyPump in comparison with the BioPump and to investigate the impact of
      different CPB circuit volumes on hemodilution, coagulation, and the inflammatory
      response. Twelve 1-week-old piglets (3.4 +/- 0.2 kg) were used. The circuit
      comprised a centrifugal pump, a membrane oxygenator, and a cardiotomy reservoir.
      Cardiopulmonary bypass was conducted with mild hypothermia at 150 ml/kg/min for 3
      hours. Transfusion was not performed. Priming volume was 68 ml for the circuit
      with the TinyPump and 111 ml for the circuit with the BioPump. Although the
      TinyPump required higher speed, plasma free hemoglobin levels after CPB were not
      different between the groups. After CPB, the TinyPump group had a significantly
      higher hematocrit (27% +/- 3% vs. 23% +/- 3%) and lower platelet reduction rate,
      lower thrombin-antithrombin complex levels, and lower interleukin-6 levels.
      Better lung compliance with less water content was observed in the TinyPump
      group. The TinyPump maintained CPB with acceptable hemolysis and lower
      inflammatory responses. This miniaturized CPB circuit may make transfusion-free
      open heart surgery feasible in neonates and would help to prevent postoperative
      organ dysfunction.

PMID- 18043146
TI  - The effect of preprocessing stored red blood cells on neonates undergoing
      corrective cardiac surgery.
AB  - This study compared the effect of unprocessed and processed packed red blood
      cells (PRBCs) with the continuous autotransfusion system (CATS) during neonate
      heart surgery. Sixteen neonatal patients undergoing cardiac surgery were randomly
      divided into two groups: unprocessed PRBC (C group, n = 8); processed PRBC (P
      group, n = 8). The CATS was employed perioperatively. Series laboratory and
      clinical parameters, including levels of hematocrit, blood potassium, blood
      glucose, blood lactate, acid-base, and total priming volume of PRBC, were used to
      compare the effect between the two groups. Before CPB, the hematocrit of
      processed PRBCs in P group was significantly higher than those in C group (p <
      0.01), and the concentrations of potassium, blood glucose, and lactate of
      processed PRBCs in P group were significantly lower than those in C group (p <
      0.01). At the beginning and the end of CPB, the hematocrit levels in P group were
      all higher than those in C group (p < 0.05); lactate levels in P group were
      significantly lower than those in C group at the beginning of CPB (p < 0.01), and
      lower than that of C group at the end of CPB (p < 0.05). The total priming of
      PRBCs in P group was significantly less than that in C group (p < 0.01).
      Perioperative processing with CATS provided a high-quality RBC concentration,
      decreased the total priming of PRBCs, providing increased high-quality blood
      salvage during neonatal CPB procedure.

PMID- 18043147
TI  - Moderate hypothermia with low flow rate cardiopulmonary bypass used in surgeries
      for congenital heart defects.
AB  - Low flow rate perfusion has been recommended in profound hypothermic
      cardiopulmonary bypass (CPB) in recent years. However, most patients with
      congenital heart defects are still operated on under moderate hypothermic CPB,
      where high flow rate perfusion has been adopted by most perfusionists. Fifty
      patients with congenital heart defects, ranging from 1 to 11 yr of age and 6.5 to
      25 kg of weight, were included in the trial. Once on CPB, a high flow rate of
      2.37 +/- 0.39 L/min/m was used to cool the patient to 27.3 degrees C +/- 0.84
      degrees C rectal temperature, followed by a low flow rate of 1.31 +/- 0.09
      L/min/m until the main intracardiac repair was completed and rewarming started.
      High flow rate was still used in rewarming the patients to a rectal temperature
      of 35 degrees C-36 degrees C. The total CPB, cross-clamp, and low flow rate
      perfusion time were 86.4 +/- 26.6, 46.4 +/- 22.3, and 40.7 +/- 22.4 min,
      respectively. After 24-99 min low flow rate perfusion, venous oxygen saturation
      remained above 80% for all the patients, and lactate concentration did not
      increase. Only three patients showed slight metabolic acidosis during CPB and
      required an extra 6-12 mEq sodium bicarbonate. Average urine output was 199 +/-
      155 (50-600) ml during CPB. All patients recovered well after operation. No
      surgical death or neurologic complications occurred. Low flow rate perfusion
      might be safely used in moderate hypothermic CPB as long as the oxygen saturation
      of returned venous blood was kept above 80%.

PMID- 18043148
TI  - Anatomic fit assessment for the Penn State pediatric ventricular assist device.
AB  - This investigation determined the ages and weights of children that could be
      supported with 12 and 25 ml Penn State pediatric ventricular assist devices
      (PVADs) using 6, 8, and 10 mm outlet cannulas and grafts. Future patients will be
      matched to devices based on cardiac output (CO) and ascending aortic diameter
      (AA). These were calculated for children 0-10 years with regression formulas
      given as clinical standards [<5 kg, CO = 0.2171(kg) + 0.0703], [>5 kg, CO = 3.06
      (m2) + 0.37], [AA = -0.0427 + 14.54 (m2)1/2]. The 12 ml PVAD will be useful for
      patients from approximately birth to 3-8 months, weighing 2-7 kg, and having 0.5
      1.4 L/min CO; the 25 ml PVAD will be for children 2-6 months to 5-9 years old,
      weighing 6-23 kg, and having 1.3-3.0 L/min of CO. The 6 mm outlet graft will fit
      children from 0 to 12 months, weighing 2-8 kg; the 8 mm graft from 0 to 47
      months, weighing 4-14 kg; and the 10 mm graft for children 4 months to 8 years,
      weighing 8-21 kg.

PMID- 18043149
TI  - Absence of rapid deployment extracorporeal membrane oxygenation (ECMO) team does
      not preclude resuscitation ecmo in pediatric cardiac patients with good results.
AB  - We evaluated the results of using extracorporeal membrane oxygenation (ECMO) as
      resuscitation for cardiac patients undergoing cardiopulmonary resuscitation (CPR)
      in our setting where neither perfusionists nor surgeons are always on site, and
      no circuit may be ready. Between 2003 and 2006, we used ECMO for all cardiac
      patients who underwent cardiac arrest in the pediatric intensive care unit (PICU)
      or Cath Laboratory. We reviewed retrospectively 14 consecutive files (15
      episodes). Mean CPR time before ECMO institution was 44 minutes (10-110 minutes).
      The surgeons, perfusionist, and scrub nurse, not on site for three of these
      patients, had to be called in simultaneously with institution of CPR. Two died on
      ECMO, the third one was successfully transplanted after 5 days. Globally, 10
      patients could be weaned (66%). Eight patients (57%) survived to hospital
      discharge, seven without obvious neurological damage. One patient was bridged to
      a left ventricular assist device (LVAD) and was eventually successfully
      transplanted. He had an ischemic brain lesion with good recuperation and no
      sequel. We obtained good results with resuscitation ECMO in our setting where a
      permanently on-site rapid deployment ECMO team is not present at all times.

PMID- 18043150
TI  - The pediatric mechanical circulatory support program in Innsbruck, Austria, and
      the impact of such programs on lack of donor hearts in Europe.
AB  - Strategy and results of the Innsbruck Mechanical Circulatory Support Program are
      presented, and the impact of such programs on pediatric heart transplantation
      (HTX) in Europe is discussed. Venoarterial extracorporeal membrane oxygenation
      (vaECMO) and ventricular assist devices (VADs) were used in 21 pediatric patients
      (median age 3.3 years, 2 days to 17 years) for acute heart failure (AHF)
      following a bridge or bridge-to-bridge strategy. Twelve patients were treated
      with vaECMO: eight were weaned after 2-10 days, two died, and two were switched
      to a VAD. Of the last, one was weaned 47 days later and the other underwent HTX
      168 days later. In nine patients, VAD was implanted without preceding vaECMO. One
      such patient died (cerebral hemorrhage) after 236 days; of the remaining eight
      patients three were weaned and five underwent HTX. Waiting time for HTX (high
      urgency status) varied from 4 to 372 days. Fifteen patients were discharged
      (follow up: 2-74 months); 14 are doing very well (New York Heart Association
      (NYHA) Functional Classification Class I, neurologically normal), whereas one
      suffers from severe neurologic damage, presumably from resuscitation before
      vaECMO. Data from Eurotransplant on pediatric HTX in 2004, 2005, and 2006 (33,
      49, and 34 transplanted hearts, respectively; recipients <16 years of age) are
      discussed. Mechanical circulatory support (MCS) substantially improves survival
      with AHF in pediatric patients. Medium-term support (up to 400 days in our
      patients) is possible and outcome of survivors is excellent. Wide spread use of
      MCS might slightly aggravate the lack of donor organs, which could result in
      longer support times.

PMID- 18043151
TI  - Use of mechanical circulatory support in pediatric patients with acute cardiac
      graft rejection.
AB  - Patients suffering from acute cardiac graft rejection can die because of
      hemodynamic collapse while being treated with vigorous immunosuppressive
      therapies. There is little pediatric data on the use of mechanical circulatory
      support (MCS) in patients with acute cardiac graft rejection accompanied by
      hemodynamic instability. This report reviews our experience using MCS in patients
      with severe acute allograft rejection and cardiogenic shock. Between July 1995
      and December 2006, 7 of 117 heart transplant recipients (6%) had MCS placed in 8
      cases of acute graft rejection with hemodynamic instability. Devices used were
      BioMedicus (five), Thoratec (two), and extracorporeal membrane oxygenation
      machine (one). Mean age was 12 +/- 6.6 years. Median duration of support was 7.5
      days (range, 3-28 days). Medical therapy applied included pulse steroids (eight),
      antithymocyte globulin (five), intravenous immunoglobulins (five), and
      plasmapheresis (five). Eighty-eight percent (seven of eight cases) weaned from
      MCS. Five patients weaned to recovery and two were bridged to retransplant. Five
      of the seven patients weaned (71%) were discharged home, all with normal left
      ventricular function. Median follow-up was 3.0 years (4.5 months to 3.5 years).
      One-year survival is 50% and 3 year survival is 38%. Mechanical circulatory
      support can be applied in patients with acute cardiac graft rejection causing
      hemodynamic instability with acceptable weaning and discharge rates.
      Unfortunately, late survival for this cohort remains poor.

PMID- 18043152
TI  - Pulsatile perfusion during cardiopulmonary bypass procedures in neonates,
      infants, and small children.
AB  - Multiple factors influence the outcome of cardiopulmonary bypass (CPB) procedures
      in pediatric patients with congenital heart defects. The benefit of pulsatile
      over nonpulsatile perfusion is one such factor that continues to be widely
      debated among researchers, perfusionists, and surgeons. However, by accurately
      measuring pulsatile flow in terms of energy equivalent pressure and surplus
      hemodynamic energy, pulsatile perfusion is clearly seen to replicate the
      physiologic heart in a manner unparalleled by nonpulsatile perfusion. Studied
      benefits of pulsatile perfusion in pediatric patients include increased vital
      organ blood flow and improvement in postoperative recovery. Also, the components
      of the extracorporeal circuit used in CPB are directly related to pulsatility and
      have a profound effect on hemodynamics in the circuit and the patient. Therefore,
      pulsatility and surplus hemodynamic energy delivery to the patient can be
      maximized by choosing the best performing heart-pumps, oxygenators, arterial
      filters, and cannulae. Furthermore, in using the most optimal circuit components
      available, the CPB procedure under pulsatile perfusion can proceed efficiently.
      Currently, the outcomes resulting from pulsatile perfusion in pediatric and adult
      patients, as well as animal models, are well documented. However, more
      multilaboratory efforts are necessary to understand and further validate the
      benefits of pulsatile perfusion in pediatric patients.

PMID- 18043153
TI  - A simple solution is "prime" for fetal cardiopulmonary bypass.
AB  - Worsening fetal gas exchange is the hallmark of frequently observed placental
      dysfunction after fetal bypass. Several factors influence this pathophysiology,
      but the optimal prime constituents for fetal bypass have yet to be defined.
      Calcium and sodium bicarbonate are frequently added to prime solutions for
      adjustments toward physiologic values. We examined whether similar manipulations
      are warranted with fetal bypass. Ovine fetuses (n = 10) at 104-110 days'
      gestation were placed on bypass for 30 minutes. Calcium chloride and sodium
      bicarbonate were added to adjust prime ionized calcium and pH. Fetal hemodynamics
      and arterial blood gases were collected immediately before, and 15 and 30 minutes
      on bypass. Statistical significance was determined by Student's t test and best
      fit correlations. Calcium addition negatively correlated with fetal pH (R >or=
      0.63) and po2 (R >or= 0.41), and displayed a robust positive correlation with
      pco2 (R = 0.88) during bypass. Similarly, bicarbonate addition revealed
      correlations for pco2 (R >or= 0.70) and po2 (R >or= 0.57), with a strong negative
      correlation to umbilical blood flow (R >or= 0.75). Calcium addition to the prime
      adversely affects fetal gas exchange worsening acidosis during fetal bypass.
      Bicarbonate addition to the prime is also detrimental to the fetus resulting in
      greater CO2 production and impaired hemodynamics.

PMID- 18043154
TI  - The Cleveland Clinic PediPump: anatomic modeling and virtual fitting studies in a
      lamb model.
AB  - Implantation of ventricular assist devices (VADs) is challenging in small
      patients with limited space in the chest. We created three-dimensional models of
      lambs to facilitate fitting of the PediPump, a pediatric VAD currently under
      development. Serial computed tomography (CT) scans were acquired at multiple time
      points (n = 8) for three lambs. Digital models were created using these CT
      datasets and three-dimensional image processing software (Mimics, Materialise).
      Pixels representing the heart and chest wall were rendered as three-dimensional
      models. Using three-dimensional model manipulation software (Magics RP,
      Materialise), on-screen models of extravascular and intravascular VADs were
      placed in right, left and biventricular support configurations to determine
      optimal placement. A cannulation strategy was established and in some cases three
      dimensional models of the inflow and outflow grafts were created. After the final
      CT study, an open-chest fitting study was performed using rapid prototype models
      of the pediatric VAD and cannulas. The pump location and orientation predictions
      from the virtual fitting studies matched those determined at the time of the open
      chest fitting studies. Using three-dimensional modeling, we have established a
      fitting protocol that facilitates animal implantations; the same modeling
      techniques may be useful for device fitting in humans.

PMID- 18043155
TI  - A novel mechanical lung assist system sustains primary bidirectional
      cavopulmonary shunt circulation in pigs.
AB  - Primary creation of a bidirectional cavopulmonary shunt (BCPS), which provides a
      stable in-series circulation, might improve survival in patients with hypoplastic
      left heart syndrome. However, pulmonary vascular immaturity and high pulmonary
      vascular resistance must be overcome to achieve a successful primary neonatal
      BCPS. This study tested the hypothesis that a novel mechanical lung assist (MLA)
      system would permit a primary BCPS in juvenile pigs. A BCPS (1(1/2) ventricle
      repair physiology) was created in nine 4-5-week-old pigs (mean weight 17.9 kg),
      followed by MLA with a miniature centrifugal pump and a hand-made double-lumen
      cannula for 2 hours. Systemic and cerebral hemodynamic and metabolic data were
      evaluated. A mean BCPS flow of 331 +/- 56 ml/min was obtained with a mean pump
      speed of 3899 +/- 306 rpm at 30 minutes after MLA initiation. Adequate
      oxygenation, ventilation, and hemodynamics were maintained. Transcranial Doppler
      ultrasound demonstrated consistent pre- and postoperative peak systolic and
      diastolic velocities of the middle cerebral artery, indicating sustained cerebral
      perfusion pressure. This study demonstrated that the MLA is able to sustain a
      high-resistance BCPS and provides a strategy or rationale for developing a
      primary neonatal cavopulmonary connection in appropriately selected neonates with
      congenital heart disease.

PMID- 18043156
TI  - Detection and classification of gaseous microemboli during pulsatile and
      nonpulsatile perfusion in a simulated neonatal CPB model.
AB  - We compared the effects of perfusion modes (pulsatile vs. nonpulsatile) on
      gaseous microemboli delivery using the Emboli Detection and Classification (EDAC)
      Quantifier at postpump, postoxygenator, and postarterial filter sites in a
      simulated pediatric cardiopulmonary bypass (CPB) model. The mock loop was
      subjected to five different pump flow rates of equal 100 ml/min intervals,
      ranging from 400 to 800 ml/min. When the target pump flow rate was achieved, 5 cc
      air was introduced into the venous line. The EDAC system recorded gaseous
      microemboli counts simultaneously at three locations in 5-minute intervals.
      Regardless of the type of perfusion mode, when the pump flow rate was increased,
      more gaseous microemboli were generated at postpump site. Compared with
      nonpulsatile flow, pulsatile flow did deliver significantly more gaseous
      microemboli at postpump site, but there was no difference between two groups at
      postoxygenator and postarterial filter sites. Capiox Baby-RX hollow-fiber
      membrane oxygenator significantly reduced the gaseous microemboli counts in both
      groups at all five pump flow rates with either pulsatile flow or nonpulsatile
      flow in this model. Our results suggest that using this novel EDAC system, we
      could detect the size of gaseous microemboli, as small as 10 microm, and the
      percentage of detected gaseous microemboli, <40 microm, was about 90% in total
      gaseous microemboli counts at any flow rate with pulsatile or nonpulsatile flow.

PMID- 18043157
TI  - The PediPump: a versatile, implantable pediatric ventricular assist device-update
      III.
AB  - The PediPump is a passive magnetic bearing, mixed flow, rotary ventricular assist
      device designed to provide support for the entire range of patient sizes
      encountered in pediatrics. Blood enters axially at the inlet and is accelerated
      and turned in the impeller to exit the pump at an intermediate angle. The size of
      the PediPump facilitates standard cannulation strategies with substantially
      downsized components. The program pursues three specific objectives: 1) System
      engineering: Progress within the last year has focused on the assembly and
      testing of PediPump prototypes. Initial in vitro hydraulic performance and
      hemolysis testing were judged satisfactory. 2) Anatomic fitting studies: As part
      of the PediPump program, three-dimensional modeling techniques based on routine,
      clinically obtained computerized tomography (CT) scans have been developed.
      During 2006, the same techniques developed for clinical scans were applied to CT
      scans obtained from sheep to guide the presurgical planning. 3) Animal studies:
      Animal implantation of PediPump prototypes commenced in July 2006. A total of
      four 6 hour acute studies were performed throughout the remainder of the year. In
      vivo performance was satisfactory and compared well with the in vitro results.
      Hemolysis levels were low.

PMID- 18043158
TI  - Mechanical cavopulmonary assist for the univentricular Fontan circulation using a
      novel folding propeller blood pump.
AB  - A blood pump specifically designed to operate in the unique anatomic and
      physiologic conditions of a cavopulmonary connection has never been developed.
      Mechanical augmentation of cavopulmonary blood flow in a univentricular
      circulation would reduce systemic venous pressure, increase preload to the single
      ventricle, and temporarily reproduce a scenario analogous to the normal two
      ventricle circulation. We hypothesize that a folding propeller blood pump would
      function optimally in this cavopulmonary circulation. The hydraulic performance
      of a two-bladed propeller prototype was characterized in an experimental flow
      loop using a blood analog fluid for 0.5-3.5 lpm at rotational speeds of 3,600
      4,000 rpm. We also created five distinctive blood pump designs and evaluated
      their hydraulic performance using computational fluid dynamics (CFD). The two
      bladed prototype performed well over the design range of 0.5-3.5 lpm, producing
      physiologic pressure rises of 5-18 mm Hg. Building upon this proof-of-concept
      testing, the CFD analysis of the five numerical models predicted a physiologic
      pressure range of 5-40 mm Hg over 0.5-4 lpm for rotational speeds of 3,000-7,000
      rpm. These preliminary propeller designs and the two-bladed prototype achieved
      the expected hydraulic performance. Optimization of these configurations will
      reduce fluid stress levels, remove regions of recirculation, and improve the
      hydraulic performance of the folding propeller. This propeller design produces
      the physiologic pressures and flows that are in the ideal range to mechanically
      support the cavopulmonary circulation and represents an exciting new therapeutic
      option for the support of a univentricular Fontan circulation.

PMID- 18043159
TI  - Feasibility of a TinyPump system for pediatric CPB, ECMO, and circulatory
      assistance: hydrodynamic performances of the modified pump housing for
      implantable TinyPump.
AB  - The TinyPump is a miniature centrifugal blood pump with an extremely small
      priming volume of 5 ml, allowing blood transfusion free cardiopulmonary bypass as
      well as extracorporeal membrane oxygenation in pediatric patients. In this study,
      a new pump housing with the angled inlet port (25 degrees toward impeller center
      with respect to the flow axis) was designed to optimize the pump displaced volume
      and to extend the application of the TinyPump to implantable support The fluid
      dynamic performance analysis revealed that the head pressure losses increased
      from 3 to 17 mm Hg in comparison with straight port design as the pump rotational
      speed increased from 2,000 to 4,000 rpm. This was probably caused by perturbed
      flow patterns at the site of the inlet bent port area and streamline hitting the
      off-center of the impeller. No significant effect on pumping efficiency was
      observed because of modification in inlet port design. Modification in the inflow
      and outflow port designs together with the drive mechanism reduces the height of
      the pump system, including the motor, to 27 mm yielding the displaced volume of
      68 ml in comparison with 40 mm of the paracorporeal system with the displaced
      volume of 105 ml. Further analysis in terms of hemolytic as well as
      antithrombogenic performance will be carried out to finalize the housing design
      for the implantable version of the TinyPump.

PMID- 18043160
TI  - In vitro evaluation of the TandemHeart pediatric centrifugal pump.
AB  - The pediatric TandemHeart pump is being developed for short-term circulatory
      support of patients varying in size from 2 to 40 kg. The pump withdraws blood
      from the left atrium via cannula inserted percutaneously, either through the
      right internal jugular vein or transhepatically, and pumps the blood back into
      the arterial system via the carotid or femoral artery. High resolution
      stereolithography (SLA) was used to create an upper housing and impeller design,
      which were assembled into a functional pump prototype. Pressure-flow
      characteristics of the pump were determined in a blood analogue solution and
      compared with the pressure-flow requirements of the intended cannulation. At
      5,500 rpm, the pump was able to generate 0.4 L/min of flow with a pressure rise
      of 325 mm Hg and 2.0 L/min with a pressure rise of 250 mm Hg. The hydraulic
      performance of the pump will enable at least 50% of cardiac output when the
      arterial cannula is placed in the carotid artery. The hemolysis of the
      TandemHeart pediatric pump at 5,500 rpm was compared with the BP-50 pediatric
      centrifugal pump in vitro using bovine blood flowing at 0.4 L/min against 250 mm
      Hg. The TandemHeart pump produced a similar increase in plasma free hemoglobin
      levels during the duration of the 6 hour test.

PMID- 18043161
TI  - Numerical design and experimental hydraulic testing of an axial flow ventricular
      assist device for infants and children.
AB  - Mechanical circulatory support options for infants and children are very limited
      in the United States. Existing circulatory support systems have proven successful
      for short-term pediatric assist, but are not completely successful as a bridge-to
      transplant or bridge-to-recovery. To address this substantial need for
      alternative pediatric mechanical assist, we are developing a novel, magnetically
      levitated, axial flow pediatric ventricular assist device (PVAD) intended for
      longer-term ventricular support. Three major numerical design and optimization
      phases have been completed. A prototype was built based on the latest numerical
      design (PVAD3) and hydraulically tested in a flow loop. The plastic PVAD
      prototype delivered 0.5-4 lpm, generating pressure rises of 50-115 mm Hg for
      operating speeds of 6,000-9,000 rpm. The experimental testing data and the
      numerical predictions correlated well. The error between these sets of data was
      found to be generally 7.8% with a maximum deviation of 24% at higher flow rates.
      The axial fluid forces for the numerical simulations ranged from 0.5 to 1 N and
      deviated from the experimental results by generally 8.5% with a maximum deviation
      of 12% at higher flow rates. These hydraulic results demonstrate the excellent
      performance of the PVAD3 and illustrate the achievement of the design objectives.

PMID- 18043162
TI  - Preconditioning with Na+/H+ exchange inhibitor HOE642 reduces calcium overload
      and exhibits marked protection on immature rabbit hearts.
AB  - Inhibition of Na/H exchanger isoform-1 (NHE1) has shown significant protection in
      adult myocardium during ischemia/reperfusion injury; however, the effect is
      unclear in immature myocardium. We evaluated the effects of HOE642 (a potent,
      highly selective NHE1 inhibitor) preconditioning on immature rabbit hearts.
      Twenty immature (2-3 weeks old) New Zealand white rabbits were randomly divided
      into the control group (n = 10) and the HOE642 preconditioning group (n = 10).
      The immature isolated hearts were subjected to 45 minutes of normothermic global
      ischemia plus 60 minutes of reperfusion after being established on the
      Langendorff apparatus. During reperfusion, the recovery rates of cardiac function
      (LVDP, +dp/dtmax, -dp/dtmax, and coronary flow) were about 90% in the HOE642
      treated group and about 50% in the control group (p < 0.05). HOE642
      preconditioning can significantly decrease the release of cardiac specific
      enzymes CK, CK-MB and LDH (p < 0.05) and the myocardial water content (p < 0.05).
      Meanwhile, HOE642 markedly attenuated intracellular calcium overload (265.8 +/-
      41.1 vs. 500.7 +/- 60.8 mg/kg dry wt) (p < 0.01). The blinded ultrastructural
      assessment under transmission electron microscopy illustrated that
      preconditioning with HOE642 produced evident myocyte salvage. This study
      demonstrates that preconditioning with HOE642 provides a significant protection
      during ischemia/reperfusion injury in immature myocardium, mostly by reducing
      myocardial calcium overload.

PMID- 18043163
TI  - Initial acute in vivo performance of the Cleveland Clinic PediPump left
      ventricular assist device.
AB  - The PediPump is a small ventricular assist device (VAD) with a hydraulic output
      range designed to support children from newborns to adolescents. The present
      report describes our initial evaluation of the PediPump as a left VAD in an acute
      sheep model. The PediPump was implanted in two sheep (50.8 and 62.7 kg). Pump
      speed was adjusted to achieve a flow of 2 L/min with the naturally occurring
      preload and afterload conditions to evaluate pump performance under a steady
      hemodynamic state for 4 hours. Upon completion, pump performance was evaluated
      under various blood pressure and heart rate conditions. During steady-state
      evaluations, the ascending aortic flow and pump speed varied slightly depending
      on systemic arterial pressure variations. During the hemodynamic manipulation
      studies, flows ranged between 0.5 and 3.2 L/min with pump speeds of 5,200-16,200
      rpm and motor current of 0.06-0.75 A. The PediPump demonstrated good initial
      hemodynamic performance for use as an implantable left VAD. However, some
      depositions were detected at the time of explanation, mainly at the rear of the
      pump. We are continuing with further acute studies to evaluate pump performance
      in anticipation of beginning chronic studies to evaluate long-term
      biocompatibility.

PMID- 18043165
TI  - Comparison of four different pediatric 10F aortic cannulae during pulsatile
      versus nonpulsatile perfusion in a simulated neonatal model of cardiopulmonary
      bypass.
AB  - We compared four commercially available 10F pediatric aortic cannulae with
      different geometric designs (DLP-Long tip, DLP-Short tip, RMI-Long tip, and
      Surgimedics-Short tip) during pulsatile versus nonpulsatile perfusion in terms of
      pressure drops and surplus hemodynamic energy (SHE) levels in an in vitro
      neonatal model of cardiopulmonary bypass. The pseudo patient was subjected to
      seven pump flow rates at 100 ml/min increments in the 400-1,000 ml/min range. A
      total of 44 experiments (n = 22, nonpulsatile; n = 22, pulsatile) were performed
      at each of the seven flow rates. Surgimedics had significantly higher pressure
      drops than the other three cannulae at various flow rates during nonpulsatile and
      pulsatile perfusion, respectively. When the perfusion mode was changed from
      nonpulsatile to pulsatile flow, SHE levels at both precannula and postcannula
      sites increased seven to nine times at all flow rates in all four cannulae.
      Surgimedics generated a significant lower SHE level when compared with the other
      three cannulae at all flow rates at both precannula and postcannula sites. The
      results suggest that different geometries of aortic cannulae have a significant
      impact on pressure drops of the cannulae as well as hemodynamic energy generation
      and delivery. Pulsatile perfusion generates more "extra" hemodynamic energy when
      compared with the nonpulsatile perfusion mode with all four cannulae used in this
      study.

PMID- 18043164
TI  - Assessment of hydraulic performance and biocompatibility of a MagLev centrifugal
      pump system designed for pediatric cardiac or cardiopulmonary support.
AB  - The treatment of children with life-threatening cardiac and cardiopulmonary
      failure is a large and underappreciated public health concern. We have previously
      shown that the CentriMag is a magnetically levitated centrifugal pump system,
      having the utility for treating adults and large children (1,500 utilized
      worldwide). We present here the PediVAS, a pump system whose design was modified
      from the CentriMag to meet the physiological requirements of young pediatric and
      neonatal patients. The PediVAS is comprised of a single-use centrifugal blood
      pump, reusable motor, and console, and is suitable for right ventricular assist
      device (RVAD), left ventricular assist device (LVAD), biventricular assist device
      (BVAD), or extracorporeal membrane oxygenator (ECMO) applications. It is designed
      to operate without bearings, seals and valves, and without regions of blood
      stasis, friction, or wear. The PediVAS pump is compatible with the CentriMag
      hardware, although the priming volume was reduced from 31 to 14 ml, and the port
      size reduced from 3/8 to (1/4) in. For the expected range of pediatric flow (0.3
      3.0 L/min), the PediVAS exhibited superior hydraulic efficiency compared with the
      CentriMag. The PediVAS was evaluated in 14 pediatric animals for up to 30 days,
      demonstrating acceptable hydraulic function and hemocompatibility. The current
      results substantiate the performance and biocompatibility of the PediVAS cardiac
      assist system and are likely to support initiation of a US clinical trial in the
      future.

PMID- 18043166
TI  - Pulsatile versus nonpulsatile flow to maintain the equivalent coronary blood flow
      in the fibrillating heart.
AB  - How much flow is required by a nonpulsatile pump to match the coronary blood flow
      equivalent to that of pulsatile pump? A cardiopulmonary bypass circuit from the
      right atrium to the ascending aorta was constructed in a ventricular fibrillation
      model using 13 Yorkshire swine. The animals were randomly divided into two
      groups: CONTROL (pulsatile T-PLS, n = 7) or EXPERIMENTAL (nonpulsatile Biopump, n
      = 6). The hemodynamic data at mid-LAD level was measured with a flow meter at
      baseline and every 20 minutes after pump flow initiation. The pump flow was
      started from 2 L/min in both groups (67 +/- 8 in CONTROL and 70 +/- 9 ml/kg/min
      in EXPERIMENTAL; p = NS), and the pump flow of the EXPERIMENTAL group was
      increased to match the coronary flow of the CONTROL group. To maintain mean
      velocity and flow in the LAD, the EXPERIMENTAL group required significantly
      higher pump flow at 20, 40, and 60 minutes (84 +/- 17 vs. 67 +/- 8, 87 +/- 24 vs.
      67 +/- 8, 85 +/- 18 vs. 67 +/- 8 ml/kg/min, respectively, p < 0.05). The LAD
      diameter was substantially smaller in the CONTROL group and the resistance index
      was significantly lower in the CONTROL group at 80 minutes and 120 minutes after
      bypass (0.56 +/- 0.26 vs. 0.87 +/- 0.20 and 0.61 +/- 0.23 vs. 0.90 +/- 0.06; p <
      0.05). In conclusion, we found that the nonpulsatile pump may require 25%-28%
      higher pump flow than the pulsatile pump to maintain equivalent coronary blood
      flow.

PMID- 18043167
TI  - The effects of dopamine, ephinephrine, and esmolol on the hemodynamic energy in
      terms of the energy equivalent pressure.
AB  - The generation of pulsatile flow depends on the hemodynamic energy gradient
      rather than the pressure gradient. We hypothesized that either positive or
      negative inotropic agents can affect the hemodynamic energy, which can be
      measured using the energy equivalent pressure (EEP) and surplus hemodynamic
      energy (SHE). This study examined the change in hemodynamic energy induced by
      dopamine, epinephrine, and esmolol infusion in terms of the EEP and SHE. Dopamine
      (5, 10 microg/kg/min), epinephrine (0.02, 0.1 microg/kg/min) and esmolol (after
      bolus 1 mg/kg, 0.1, 0.3 mg/kg/min) were infused into six anesthetized dogs. The
      hemodynamic parameters were collected in the descending thoracic aorta. The mean
      arterial pressure, blood flow, EEP, and SHE increased significantly with the
      dopamine infusion. The mean arterial pressure and EEP decreased significantly
      after the esmolol infusion, while it increased after the epinephrine infusion (p
      < 0.05 respectively). There was a correlation between the EEP and flow on the
      descending aorta during the dopamine, esmolol and epinephrine infusions (p < 0.05
      respectively). In conclusion, the change in hemodynamic energy induced by
      dopamine, esmolol, and epinephrine may be expressed in terms of the EEP and SHE.
      In addition, there was a strong correlation between the EEP and flow.

PMID- 18043168
TI  - Impaired corneal wound healing associated with ketorolac 0.5% after uncomplicated
      extracapsular cataract extraction.
AB  - PURPOSE: To describe an apparent association between the use of ketorolac 0.5%
      (Acular; Allergan) for cystoid macular edema (CME) prophylaxis and impaired
      corneal wound healing in patients undergoing extracapsular cataract extraction
      (ECCE) with intraocular lens (IOL) implantation. METHODS: A retrospective case
      series reviewing 7 eyes of 7 patients who underwent uncomplicated ECCE with IOL
      implantation and were treated postoperatively with ketorolac 0.5% 4 times daily
      as a prophylactic measure against CME. RESULTS: Patients were treated with
      ketorolac 0.5% 4 times a day for an average of 30 days (range, 20-44 days) after
      uncomplicated ECCE with IOL implantation. Two eyes developed postoperative
      endophthalmitis necessitating vitreous tap with intravitreal antibiotic
      injection; 1 eye went on to require pars plana vitrectomy with corneal wound
      resuturing. One eye developed corneal wound dehiscence that required wound
      resuturing in the operating room. One eye developed an inadvertent filtering bleb
      despite the lack of postoperative suture lysis. Three others were followed up
      closely postoperatively with slit-lamp evidence of impaired wound healing,
      manifested by wound avascularity and/or wound gape, and did not require surgical
      intervention. CONCLUSIONS: The use of nonsteroidal anti-inflammatory agents for
      prophylaxis of CME after cataract surgery is an evolving trend. This
      retrospective case series showed a possible link between the use of ketorolac
      0.5% and impaired corneal wound healing, and caution is urged in the liberal use
      of this agent postoperatively after ECCE.

PMID- 18043169
TI  - The influence of chronic diabetes mellitus on the thickness and the shape of the
      anterior and posterior surface of the cornea.
AB  - PURPOSE: To determine the influence of diabetes mellitus (DM) type 1 and type 2
      on the thickness, radius of curvature, power, and asphericity of the cornea.
      METHODS: In this observational cross-sectional study, 102 patients with DM type
      1, 101 patients with DM type 2, and 69 healthy subjects were measured by means of
      Scheimpflug imaging to determine central corneal thickness and the radius and
      asphericity of the anterior and posterior corneal surfaces. Corneal power was
      calculated from these parameters. Several systemic parameters (eg, duration of
      diabetes, glycated hemoglobin, blood glucose levels, and type of medication) and
      ocular comorbidity (eg, stage of retinopathy) were recorded. RESULTS: Patients
      with DM type 1 and 2 had significantly smaller posterior corneal radii (P < 0.05)
      than those of healthy subjects (men: 6.49/6.48/6.64 mm; women: 6.36/6.30/6.49
      mm). As a result, the optical power of the posterior corneal surface of the
      patients with diabetes differed from that of the healthy subjects (P < 0.01; men:
      DM, -6.2 D; healthy, -6.0 D; women: DM, -6.3 D; healthy, -6.2 D). However,
      corneal thickness, anterior radius and asphericity, and overall corneal power did
      not differ significantly between the groups. Furthermore, none of the systemic
      factors or ocular comorbidity had any influence on the corneal thickness or
      shape. CONCLUSIONS: DM affects the posterior corneal radius, resulting in a small
      change in posterior corneal power. However, chronic DM does not seem to
      significantly influence the overall corneal power.

PMID- 18043170
TI  - Modified Ruiz procedure for reducing high astigmatism after penetrating
      keratoplasty.
AB  - PURPOSE: To evaluate the refractive, keratometric, and visual outcomes of a
      modified Ruiz procedure in patients with high astigmatism after penetrating
      keratoplasty (PKP). METHODS: Retrospective cohort study with 26 eyes of 24
      patients. A modified Ruiz incision pattern was used. Two paired arcuate
      incisions, centered on the preoperative cylinder axis, were performed over 2
      o'clock hours (60 degrees) within the graft. The median optical zone was 4.5 mm
      (range, 3-5 mm). Subsequently, 4 radial cuts were made. The depth of all cuts was
      90%-95% of the central corneal thickness. The follow-up time was 3 months.
      RESULTS: The mean preoperative subjective cylinder was 8.75 +/- 3.05 D,
      decreasing to 5.31 +/- 3.12 D postoperatively. Three months after the procedure,
      53.8% of the eyes had <5.0 D of refractive astigmatism and 47% of eyes had <5.0 D
      of keratometric astigmatism. For the refractive data, the mean correction index
      was 1.95; the mean index of success was 1.27. The mean reduction in spherical
      equivalent was 1.95 D (60.5%). The mean best-corrected visual acuity (BCVA) was
      0.61 and did not change significantly. Three eyes gained 2 or more lines of BCVA,
      and 1 eye lost 2 or more lines of BCVA. There was no difference in subgroup
      analysis of eyes treated with 4- (13 eyes) or 5-mm (12 eyes) optical zones.
      CONCLUSIONS: The modified Ruiz procedure is an effective method to reduce high
      astigmatism after PKP. However, the results were widely scattered, and the
      patients need to be informed about the unpredictable outcome and its
      consequences.

PMID- 18043171
TI  - Bandage contact lens and topical indomethacin for treating persistent corneal
      epithelial defects after vitreoretinal surgery.
AB  - PURPOSE: Persistent corneal epithelial defect is a complication of vitreoretinal
      surgery. We assessed the efficacy of using bandage contact lenses in conjunction
      with topical indomethacin to facilitate wound healing and control pain safely.
      METHODS: Patients presenting with a persistent corneal epithelial defect after
      vitreoretinal surgery were assigned randomly to 1 of 2 treatment groups. Patients
      in both groups received a therapeutic contact lens and chloramphenicol eyedrops,
      whereas group A received indomethacin eyedrops and group B received placebo
      eyedrops. This study was conducted in a single-masked randomized fashion.
      Patients were evaluated daily to monitor subjective symptoms and to measure the
      maximum and minimum dimensions of the epithelial defects. RESULTS: Sixteen
      patients were analyzed. The subjective evaluation of photophobia, foreign-body
      sensation, and tearing on the day after starting treatment did not differ
      significantly between the 2 groups (P > 0.05), whereas the difference in the mean
      pain decrease between groups A and B at day 1 was significant (P = 0.01). The
      rate of epithelial healing quantified as the days needed to heal the epithelial
      defect did not differ between the 2 groups (P = 0.823). CONCLUSIONS: Our study
      showed that topical indomethacin ophthalmic solution improves comfort in patients
      with a persistent corneal epithelial defect (after vitreoretinal surgery) treated
      with bandage contact lenses.

PMID- 18043172
TI  - Delayed epithelial healing after keratoplasty for lattice corneal dystrophy.
AB  - PURPOSE: To compare the time necessary for complete epithelial healing after
      penetrating keratoplasty carried out for various corneal dystrophies. METHODS: In
      a retrospective single-center study, 679 eyes that underwent nonmechanical
      keratoplasty were evaluated concerning postoperative epithelial healing time. On
      the basis of corneal pathology, the eyes were divided into 5 groups: group 1,
      lattice dystrophy (n = 9); group 2, macular dystrophy (n = 16); group 3, Fuchs
      dystrophy (n = 207); group 4, granular dystrophy (n = 13); group 5, keratoconus
      (n = 434). After keratoplasty, the time necessary for complete healing of the
      epithelial defect was compared among the groups. RESULTS: In lattice dystrophy,
      22% showed delayed healing, in contrast to 0% in granular dystrophy. Mean time
      necessary for healing in group 1 (8.8 +/- 9.4 days) was significantly longer than
      in group 2 (2.5 +/- 2.5 days, P = 0.003), group 3 (4.4 +/- 4.1 days, P = 0.09),
      group 4 (2.2 +/- 1.4 days, P = 0.003), and group 5 (3.1 +/- 2.7 days, P = 0.005).
      CONCLUSIONS: In patients with lattice dystrophy, delayed epithelial healing after
      penetrating keratoplasty may be anticipated. Patients should be counseled
      accordingly.

PMID- 18043173
TI  - Prevalence of and factors associated with pterygium in adult Chinese: the Beijing
      Eye Study.
AB  - PURPOSE: To evaluate the prevalence of pterygia and its associated factors in an
      adult Chinese population of Greater Beijing. METHODS: The Beijing Eye Study, a
      population-based prevalence study, included 4439 (83.4%) of 5324 subjects living
      in a rural area or urban region of Greater Beijing, 40+ years of age, invited to
      participate. The participants underwent a standardized examination protocol
      including corneal photography. RESULTS: A pterygium was detected in 169 (1.9%)
      eyes of 128 (2.9%) subjects. The prevalence of a pterygium was significantly
      associated with rural versus urban region (P < 0.001), age (P > 0.001), and male
      sex (P = 0.04). It was not associated with level of education (P = 0.25) or
      refractive error (P = 0.20). CONCLUSIONS: The prevalence of pterygium in Greater
      Beijing is approximately 3% among Chinese > or =40 years of age. Independent
      associations with living in a rural versus urban region, increasing age, and male
      sex suggested a correlation with outdoor work.

PMID- 18043174
TI  - An outbreak of Fusarium keratitis associated with contact lens use in the
      northeastern United States.
AB  - PURPOSE: To report an outbreak of Fusarium keratitis in contact lens (CL) wearers
      in the northeastern United States. METHODS: Over a 41-month period, all cases
      with culture-proven corneal ulceration secondary to Fusarium at 2 tertiary care
      eye centers were identified through the microbiology departments of each
      institution, and a retrospective review of charts was performed. Statistical
      analyses were performed to evaluate a possible association of Fusarium keratitis
      with specific CL and CL solution brands. RESULTS: Fifteen cases of Fusarium
      keratitis were reported at the 2 tertiary centers between July 2005 and May 2006
      (16.4 cases/yr) compared with 6 cases over the previous 30 months from January
      2003 to June 2005 (2.4 cases/yr). All 15 of the more recent cases were CL users,
      and none had a history of trauma. All 15 patients claimed use of ReNu brand
      contact lens solution when they developed keratitis. Twelve (80.0%) of 15
      patients were Acuvue soft contact lens users. Ten (66.7%) of 15 patients used tap
      water to rinse their contact lens cases. Six (40.0%) of 15 cases have thus far
      required corneal transplantation. CONCLUSIONS: The incidence of corneal
      ulceration secondary to Fusarium has increased sevenfold over the reported 11
      month period at 2 tertiary eye care centers in the northeastern United States
      compared with the previous 30 months. There seems to be an association between
      the recent outbreak of Fusarium keratitis among CL users and the use of ReNu
      contact lens solution. Medical treatment of Fusarium keratitis may be
      ineffective, and emergent penetrating keratoplasty (PKP) may be required in some
      patients. CL users and their physicians should reconsider the risks of CL use and
      discuss proper lens care techniques.

PMID- 18043175
TI  - Boston scleral lens prosthetic device for treatment of severe dry eye in chronic
      graft-versus-host disease.
AB  - PURPOSE: To determine if the Boston Scleral Lens Prosthetic Device (BSLPD)
      reduces symptoms and improves quality of life in patients with severe dry eye
      from chronic graft-versus-host disease (cGvHD). METHODS: This is a noncomparative
      interventional case series reporting 33 consecutive patients with severe dry eye
      from cGvHD, unresponsive to conventional therapy, who were fitted with the BSLPD.
      A patient survey was undertaken after lenses were dispensed and worn regarding
      the effect of scleral lens wear on their symptoms, quality of life, and
      activities of daily living. The patient population was characterized from a
      retrospective chart review. Survey data were tabulated. RESULTS: BSLPD wear
      resulted in improvement in pain, photophobia, and general quality of life in
      nearly all patients, with more than half reporting the highest improvement level
      for pain (52%) and photophobia (63%), and more than two thirds (73%) reporting
      the highest improvement level for quality of life. There was improvement in
      reading and driving in >90% of those who reported previous compromise, with >60%
      reporting the highest improvement level for each of these activities.
      CONCLUSIONS: The BSLPD mitigates symptoms and improves quality of life in
      patients with severe dry eye from cGHvD.

PMID- 18043176
TI  - Long-term outcomes of photorefractive keratectomy in eyes with previous
      epikeratophakia for keratoconus.
AB  - PURPOSE: To determine the long-term safety and effectiveness of photorefractive
      keratectomy (PRK) in the treatment of refractive errors after epikeratophakia
      (EP) for keratoconus. METHODS: Ten patients (14 eyes) who had refractive errors
      after EP for keratoconus received PRK surgery. Uncorrected visual acuity (UCVA),
      best spectacle-corrected visual acuity (BSCVA), refractive error, corneal
      astigmatism, pachymetry, corneal topography, and complications were monitored.
      RESULTS: Mean follow-up after PRK was 63.4 +/- 19.8 months. Mean spherical
      equivalent was -5.5 +/- 3.9 D before PRK, -0.9 +/- 0.5 D at 1 month after PRK,
      and -1.5 +/- 1.0 D at 3 years. Mean astigmatism was 4.2 +/- 2.1 D before PRK, 1.2
      +/- 0.5 D at 1 month after PRK, and 1.5 +/- 0.6 D at 3 years. Thirteen (93%) eyes
      had an UCVA <20/40, and 12 (86%) had a BSCVA of 20/40 or better before PRK. At 1
      year, the UCVA was 20/40 or better in 8 (57%) eyes, and the BSCVA was 20/40 or
      better in all eyes. Mean central corneal thickness was 749 +/- 35 microm before
      PRK and 621 +/- 56 mum at 3 years. During the follow-up period, haze (grade no
      more than 1.0) was observed in 2 eyes. No immune rejection episode or recurrent
      keratoconus was found. CONCLUSIONS: PRK appears to be reliable and safe for the
      correction of residual ametropia after EP for keratoconus, and the visual acuity
      can remain stable after PRK for a long time.

PMID- 18043177
TI  - A case series of contact lens-associated Fusarium keratitis in Hong Kong.
AB  - PURPOSE: To report the clinical features and management outcomes of a cluster of
      Fusarium keratitis in patients that used the Bausch & Lomb ReNu MostureLoc
      contact lens solution. METHODS: Retrospective case series. RESULTS: In a 1-year
      period starting from June 2005, we treated 12 patients with unilateral Fusarium
      keratitis in our tertiary care center. All patients were contact lens users that
      used ReNu MostureLoc contact lens solution and had no other specific predisposing
      conditions. Microbiological examination yielded growth of Fusarium spp. in 7
      patients from corneal scrapings at presentation and from 3 patients in subsequent
      corneal specimens. For 2 other patients, fungi were not detected from corneal
      scrapings, but Fusarium spp. were isolated from their contact lenses. The
      infections were treated with topical natamycin and amphotericin B eye drops and
      with systemic itraconazole in 8 patients. The infection resolved with medical
      treatment in 8 eyes, a conjunctival flap in 1 eye, and a therapeutic corneal
      graft in 1 eye. Two eyes required tectonic corneal grafts for perforation. Two of
      the 3 corneal grafts failed because of graft rejection. Final visual acuities
      ranged from count fingers to 1.0. CONCLUSIONS: This cluster of Fusarium keratitis
      seems to be related to the use of the ReNu MoistureLoc contact lens solution. The
      cure rate with medical therapy was 66%. However, corneal scarring limited visual
      recovery. This episode highlights the need for clinical vigilance when dealing
      with corneal infiltrates in contact lens users.

PMID- 18043178
TI  - Long-term reversibility of epikeratophakia.
AB  - PURPOSE: To assess the long-term reversibility of epikeratophakia. METHODS: Three
      human epikeratophakia lenticules (from 3 patients) were removed 7-14 years after
      refractive keratoplasty for aphakia (n = 1) and myopia (n = 2). Reasons for
      removal were irregular astigmatism (n = 1), opacities in the graft and host
      cornea, and progressive myopia (n = 2). After removal, 2 patients underwent
      cataract extraction and 1 underwent secondary implantation of AC-IOL. Visual
      acuity, refraction, keratometry, and corneal topography were assessed before and
      after removal of the lenticule, as well as after the cataract and IOL
      implantation, and were compared with the initial visual acuity and corneal
      curvature before epikeratoplasty. RESULTS: After removal of the lenticule, the 3
      patients regained the initial curvature of the cornea (pre-epikeratoplasty), and
      remained stable during 6 months of follow-up. Initial best-corrected visual
      acuity and refraction before epikeratoplasty were restored after removal of the
      epikeratoplasty lenticule in the aphakic patient. Original best-corrected visual
      acuity was restored in the 2 myopic cataract patients after cataract extraction
      and IOL implantation. CONCLUSIONS: In a small care series, epikeratophakia was
      found to be a reversible procedure even after 7-14 years.

PMID- 18043179
TI  - Expression of matrix metalloproteinase 2 and 9 in experimentally wounded canine
      corneas and spontaneous chronic corneal epithelial defects.
AB  - PURPOSE: To determine matrix metalloproteinase (MMP) 2 and MMP 9 expression in
      acute and chronic experimentally wounded canine corneas and keratectomy samples
      from canine patients with spontaneous chronic corneal epithelial defects
      (SCCEDs). METHODS: Mechanical debridement was performed unilaterally in 25
      healthy dogs for the acute wound study. Twenty-four hours (n = 8), 48 hours (n =
      5), 72 hours (n = 3), or 1 week (n = 9) after wounding, the dogs were euthanized.
      Debridement was performed once weekly for 8 weeks for the chronic study (n = 8).
      Therapeutic superficial keratectomies (n = 16) were performed on SCCED patients.
      Gelatin zymography and immunohistochemistry were performed. RESULTS: Acute wounds
      showed upregulation of MMP 9 at all time points. At 7 days after wounding, values
      diminished markedly but remained elevated above those of unwounded controls.
      SCCED and chronic wound samples showed a significant increase in MMP 9 compared
      with controls but were less than that of acute wounds. There was no significant
      difference between chronic wounds versus SCCED samples. Fellow control eyes
      showed significant upregulation of MMP 9 in tandem with wounded eyes. There was
      no significant difference in values for MMP 2 in wounded corneas or SCCED
      compared with those of controls. Immunhistochemistry localized MMP 9 to
      predominantly the epithelium with some staining of keratinocytes and stroma.
      CONCLUSIONS: The dog exhibits similar MMP expression during corneal wound healing
      to that of other species. The lack of significant difference in MMP expression
      between SCCED and chronic wounds suggest that MMP 2 and 9 are not involved in the
      pathophysiology of SCCED and are more likely altered secondary to a chronic
      epithelial defect.

PMID- 18043180
TI  - Experimental transplantation of corneal epithelium-like cells induced by Pax6
      gene transfection of mouse embryonic stem cells.
AB  - PURPOSE: Corneal epithelial stem cells are deficient in cases of limbal
      disorders, leading to conjunctival epithelial ingrowth, vascularization, and
      eventually visual disturbance. We introduced the eye development-associated
      transcription factor pax6 to embryonic stem (ES) cells and tested whether pax6
      transfected cells resembling purified corneal epithelial cells were applicable as
      a cell source for corneal transplantation. METHODS: pax6 cDNA with green
      fluorescence protein was electrotransfected to ES cells and the cells were
      cultured with G418 for 14 days. They were characterized by reverse transcription
      polymerase chain reaction and immunohistochemistry. The cells were transplanted
      onto experimentally damaged mouse corneas. Histologic reconstitution of the
      corneal epithelium was assessed. RESULTS: pax6-transfected cells formed a
      monolayer of epithelium-like cells in vitro. They expressed cytokeratin12, a
      specific keratin of corneal epithelial cells, E-cadherin, and CD44, which are
      important adhesion molecules of corneal epithelial cells on the cell membrane.
      They accumulated to make a colony that gave a staining pattern of reticular
      configuration for cytokeratin 12, E-cadherin, and CD44. When the cells were
      transplanted onto damaged cornea, they have been kept alive on the cornea.
      CONCLUSIONS: The purified corneal epithelium-like cells derived from ES cells
      transfected with pax6 gene adapted to the injured cornea and were kept alive on
      it. These results suggested application of ES cell-derived corneal epithelial
      cells for treating corneal injuries.

PMID- 18043181
TI  - Comparison of the bacteriostatic effects, corneal cytotoxicity, and the ability
      to seal corneal incisions among three different tissue adhesives.
AB  - PURPOSE: To compare the bacteriostatic effects, corneal cytotoxicity, and ability
      to seal corneal incisions among fibrin glue and 2 commercially available
      cyanoacrylate derivatives: N-butyl cyanoacrylate and methoxypropyl cyanoacrylate.
      METHODS: The bacteriostatic activities of these tissue glues were verified by
      measuring the zones of bacterial growth inhibition surrounding the adhesive
      droplets on agar plates inoculated with Staphylococcus aureus, Streptococcus
      pneumoniae, Pseudomonas aeruginosa, Escherichia coli, or Mycobacterium chelonae.
      Corneal cytotoxicity was tested by a direct contact method by using cultured
      bovine corneal epithelial cells, keratocytes, and corneal endothelial cells
      challenged with droplets of adhesives. Each of the cells was treated with
      droplets of adhesives. The ability to seal corneal incisions was verified by
      calculating the maximum intraocular pressure resistant to leakage of rabbit
      corneal stab wounds sealed with tissue adhesives. RESULTS: Methoxypropyl
      cyanoacrylate and N-butyl cyanoacrylate showed bacteriostatic effects against S.
      aureus, S. pneumoniae, and M. chelonae but not P. aeruginosa and E. coli. In
      contrast, fibrin glue had no such effects against either Gram-positive or 
      negative bacteria (P < 0.01). Methoxypropyl cyanoacrylate showed the highest
      levels of corneal cytotoxicity, followed by N-butyl cyanoacrylate. Fibrin glue,
      however, showed minimal cytotoxicity (P < 0.01). Methoxypropyl cyanoacrylate and
      N-butyl cyanoacrylate also displayed a greater ability to seal corneal incisions
      than that of fibrin glue (P < 0.01). CONCLUSIONS: The bacteriostatic effects,
      corneal cytotoxicity, and ability to seal corneal incisions differed among the 3
      compounds tested. These different properties should be considered when choosing
      tissue adhesives during corneal surgery.

PMID- 18043182
TI  - Fibrin glue for opposing wound edges in "Top Hat" penetrating keratoplasty: a
      laboratory study.
AB  - PURPOSE: To evaluate the advantages of fibrin glue for opposing wound edges in
      Top Hat penetrating keratoplasty (PKP). METHODS: Twenty human corneoscleral rims
      were mounted on an artificial anterior chamber. Eight corneas underwent
      traditional PKP, 6 underwent Top Hat PKP, and 6 underwent Top Hat PKP by using
      fibrin glue for opposing wound edges. Mechanical stability was evaluated after
      placement of 8 and 16 interrupted sutures. Wound bursting pressure and induced
      astigmatism were evaluated. RESULTS: In the traditional PKP group, wound bursting
      pressure was 25.2 and 59.1 mm Hg after placement of 8 and 16 sutures,
      respectively. In the Top Hat PKP, leakage occurred at 57.6 and 103.8 mm Hg after
      placement of the 8 and 16 sutures, respectively. In the Top Hat PKP + fibrin glue
      group, wound leakage occurred at 144.6 mm Hg after placement of the 8 sutures and
      at >158 mm Hg after placement of 16 sutures. The Top Hat PKP + fibrin glue group
      induced astigmatism of 2.5 D, whereas the traditional PKP group and the Top Hat
      PKP group showed an induced astigmatism of 3.1 D each. CONCLUSIONS: The use of
      fibrin glue in Top Hat PKP was found to be more mechanically stable than
      traditional sutures.

PMID- 18043183
TI  - Reconstructed corneas: effect of three-dimensional culture, epithelium, and
      tetracycline hydrochloride on newly synthesized extracellular matrix.
AB  - PURPOSE: To evaluate the influence of the 3-dimensional collagen-glycosaminogycan
      chitosan (CGC 3D) scaffold, epithelialization, and the addition of tetracycline
      hydrochloride on the ultrastructural organization, measured by the diameter and
      spacing of newly synthesized collagen I fibrils. METHODS: Little is known about
      the role of interactions between epithelial cells and fibroblasts in controlling
      the extracellular matrix of the cornea. We developed a hemicornea from a CGC 3D
      matrix cocultured with keratocytes and human epithelial cells. The keratocytes
      colonized this substrate, proliferated, and synthesized the extracellular matrix,
      reproducing a living stroma equivalent. RESULTS: Without a 3D scaffold, the
      collagen fibrils produced had an average diameter that was 42.7 nm and sigma =
      16.9 nm. In the CGC 3D scaffold, the fibrils had an average diameter of 33.4 nm,
      with little dispersion (sigma = 6.7 nm), suggesting a greater regulation. The
      epithelium permitted a significant reduction in fibril diameter and
      interfibrillar spacing. Tetracycline hydrochloride had no effect on spacing but
      did have a significant effect on fibril diameter. We found positive interactions
      between the epithelium and tetracycline hydrochloride on the regulation of
      collagen fibrils but not on spacing. The presence of epithelium led to the
      increased formation of collagens I and V in the subepithelial area of the newly
      formed matrix. Type VI collagen was localized around the keratocytes throughout
      the matrix. CONCLUSIONS: Epithelialization and the 3D scaffold had a great
      influence on the diameter of collagen I fibrils.

PMID- 18043184
TI  - Differences among strains of the Fusarium oxysporum-F. solani complexes in their
      penetration of hydrogel contact lenses and subsequent susceptibility to
      multipurpose contact lens disinfection solutions.
AB  - PURPOSE: To examine in vitro conditions for attachment and penetration of
      silicone hydrogel (SH) lenses by clinical isolates of the Fusarium oxysporum-F.
      solani complexes and the relative susceptibilities of the fusaria in the lens
      matrices to multipurpose contact lens solutions (MPSs). METHODS: SH soft contact
      lenses were soaked in Sabouraud dextrose broth (SAB) for 2 hours and transferred
      to 3.0 mL of phosphate-buffered saline (PBS). The lenses were inoculated with
      representative isolates of both complexes and incubated on a shaker at ambient
      temperature. Lenses were examined daily by light microscopy before and after
      rinsing and rubbing in MPS. Selected lenses penetrated by fungi were rinsed and
      rubbed with MPS and held in MPS for 6 hours, transferred to PBS with 0.03% SAB,
      and examined daily. RESULTS: The degree and rate of lens penetration of contact
      lenses by isolates of the F. oxysporum-F. solani complexes varied with lens type
      and the strain. Isolates obtained from patients with Fusarium keratitis produced
      on and within lenses chlamydospores that seemed similar to those observed in
      lenses actually worn by patients when they developed Fusarium keratitis. Clinical
      isolates showed greater capacities than those of a standard test strain to
      penetrate lenses and to survive exposures to various MPSs. In general, isolates
      of F. solani were more readily removed from lenses by rubbing than were isolates
      of F. oxysporum. CONCLUSIONS: The ability of Fusarium spp. to attach to and
      penetrate SH lenses in vitro varies with the lens type and strain, and this
      ability may make infectious keratitis more likely. We recommend the incorporation
      of a rubbing step in the MPS disinfection of hydrogel lenses to reduce the risk
      of fungal keratitis.

PMID- 18043185
TI  - Corneal lamellar dissection by using suture threads in porcine eyes.
AB  - PURPOSE: Lamellar dissection is one of the most delicate maneuvers in corneal
      surgery. We describe a new method that uses Ferrara ring instrumentation.
      METHODS: A 360 degrees tunnel is created at half of the stromal depth in porcine
      corneas. A suture (nylon 6-0 or Vicryl 6-0) was passed through the tunnel by
      using the Ferrara spatula. By means of alternate traction on the end of the
      suture thread, complete lamellar dissection was achieved. RESULTS: Light
      microscopy examination of the cornea confirmed that the dissection had a constant
      thickness and dissection depth. Scanning electron microscopy showed a homogeneous
      stromal surface without irregularities. CONCLUSIONS: This technique permits a
      homogeneous and safe lamellar dissection, which may prove useful in specific
      surgical procedures of the cornea.

PMID- 18043186
TI  - Complications of AlphaCor keratoprosthesis: a clinicopathologic report.
AB  - PURPOSE: To describe the clinical and histopathologic features of intractable
      secondary glaucoma induced by AlphaCor keratoprosthesis. METHODS: An elderly
      woman with pseudoexfoliation glaucoma and pseudophakic bullous keratopathy in the
      right eye had graft failures after penetrating keratoplasty. Her best-corrected
      visual acuity at presentation was counting fingers in the right eye and 20/30 in
      the left eye. Examination showed severe corneal neovascularization. Chirila
      keratoprosthesis type II was implanted in 2 stages. Ten months later, the patient
      developed dense retrocorneal membrane, 360 degrees occlusion of angles,
      intractable glaucoma, no light perception, and nasal stromal melting associated
      with partial extrusion of the keratoprosthesis. RESULTS: Histopathology revealed
      invasion of the porous material of the keratoprosthesis by reactive fibroblasts
      and multinucleated foreign-body giant cells. In the area of dehiscence, we noted
      thinning and lysis of the collagen fibers, infiltration of lymphocytes, and
      plasma cells with a sheet of fibroinflammatory tissue extending into the anterior
      chamber. CONCLUSIONS: Corneal stromal melting and retrocorneal prosthetic
      membrane formation after AlphaCor keratoprosthesis implantation led to
      intractable glaucoma and extrusion of the implant.

PMID- 18043187
TI  - Conjunctival intraepithelial neoplasia in a patient treated with tacrolimus after
      liver transplantation.
AB  - PURPOSE: To report a case of conjunctival intraepithelial neoplasia in a patient
      treated with tacrolimus after liver transplantation for hepatic carcinoma.
      METHODS: Description of the initial clinical presentation of a patient, tumor
      management, and 15-month follow-up. RESULTS: A 70-year-old man presented with a
      conjunctival intraepithelial neoplasia that developed on the site of a
      preexisting pterygium. After total surgical removal and additional application of
      mitomycin, local tumor control was achieved. CONCLUSIONS: We describe a case of
      intraepithelial conjunctival neoplasia in a patient treated with systemic
      tacrolimus. Local tumor control was achieved at 15 months after appropriate
      surgical management.

PMID- 18043188
TI  - Histologic evidence of retained fetal layer of the descemet membrane after
      presumed total removal for endothelial keratoplasty: a possible cause for graft
      failure.
AB  - PURPOSE: This is, to our knowledge, the first report of histology after failed
      Descemet-stripping endothelial keratoplasty (DSEK) surgery in a patient. We
      describe the interface histology found in a case of donor nonadherence and
      subsequent graft failure in a patient after DSEK. METHODS: An 83-year-old woman
      with a history of Fuchs dystrophy underwent DSEK surgery and subsequently
      underwent full-thickness penetrating keratoplasty (PKP) because of nonadherence
      of the donor disc and presumed graft failure. Specimens from the initial
      stripping of the Descemet membrane, the failed donor disc, and the full thickness
      of the patient's remaining cornea containing the recipient bed after her DSEK and
      PKP procedures were histologically evaluated by light microscopy. RESULTS:
      Microscopic examination of the initial stripped recipient Descemet membrane
      revealed a "delamination" of the Descemet membrane involving the fetal layer.
      After PKP, histopathologic study of the recipient button revealed residual fetal
      Descemet membrane retained on the recipient DSEK interface. Examination of the
      failed donor disc showed healthy tissue. CONCLUSIONS: In DSEK surgery, there are
      multiple reasons that the donor graft button may fail to adhere to the recipient
      posterior corneal surface. In this instance, histologic study revealed that the
      Descemet membrane was split by the stripping, and the fetal layer of the Descemet
      membrane was retained on the central part of the patient's posterior cornea.
      Despite histologically normal donor endothelial cells, the inability of the donor
      tissue to adhere may have been caused by the coating of the central recipient bed
      with retained fetal Descemet membrane.

PMID- 18043189
TI  - Granular corneal dystrophy manifesting after radial keratotomy.
AB  - PURPOSE: To report a case of granular corneal dystrophy after radial keratotomy
      (RK). METHODS: A 32-year-old man presented with white radial lines in both
      corneas. He had a history of uncomplicated RK in both eyes 8 years ago.
      Preoperative refraction had been OD -3.5-0.75 x 180 and OS -3.0-0.5 x 175. The
      cornea was reported to be clear on postoperative examinations. RESULTS:
      Postoperative uncorrected visual acuity was OD 20/30 and OS 20/40. Best-corrected
      visual acuity was 20/25 in both eyes with OD -0.5-0.5 x 60 and OS -0.75-0.5 x 80.
      Slit-lamp examination revealed discrete well-demarcated whitish lesions with
      clear intervening stroma in the central anterior cornea consistent with granular
      dystrophy. Similar opacities were present within the RK incisions. CONCLUSIONS:
      Production and deposition of such abnormal material could be due to keratocyte
      activation after RK or proliferation and migration of epithelial cells with a
      tendency to express abnormal keratoepithelin.

PMID- 18043190
TI  - Slit-lamp, confocal, and light microscopic findings of corneal siderosis.
AB  - PURPOSE: To report the clinical, histopathologic, and confocal findings of
      corneal siderosis. METHODS: A 35-year-old man presented after a car battery
      explosion with diffuse left corneal anterior stromal pigment deposition and an
      intraocular metallic foreign body of the left iris. The corneal pigment was
      analyzed by confocal microscopy and a lamellar corneal biopsy. RESULTS: Confocal
      microscopy showed the pigment to be highly reflective material in the corneal
      stroma with greatest density anteriorly. Histologic examination revealed the
      pigment to be iron with a diagnosis consistent with corneal siderosis.
      CONCLUSIONS: Corneal biopsy with Prussian blue established siderosis as the
      etiology of corneal pigmentation. A short delay in the removal of the foreign
      body contributed to the development of siderosis. The location of the foreign
      body on the iris may account for the predominant corneal involvement and relative
      sparing of the retina. Confocal microscopy may be useful in the evaluation of
      corneal siderosis.

PMID- 18043191
TI  - Corneal blood staining secondary to hemorrhagic descemet membrane detachment.
AB  - PURPOSE: To present a case of corneal blood staining due to a hemorrhagic
      Descemet membrane detachment and describe a method of surgical intervention.
      METHODS: Observation of clinical features and outcome of surgical intervention.
      RESULTS: A 72-year-old man had an anterior-chamber intraocular lens removed for
      presumed uveitis-glaucoma-hyphema syndrome, and he developed an intraoperative
      hemorrhagic detachment of the Descemet membrane attributed to peripheral corneal
      neovascularization. Corneal blood staining rapidly developed, and a partial
      thickness paracentesis was required to evacuate the lamellar hematoma and allow
      reattachment of the Descemet membrane. CONCLUSIONS: Hemorrhage from posterior
      corneal vessels can result in a hemorrhagic detachment of the Descemet membrane.
      Corneal blood staining can develop rapidly in an intracorneal or retrocorneal
      hemorrhage. The blood can be removed without incising the Descemet membrane by
      making a partial-thickness paracentesis.

PMID- 18043192
TI  - Hypopyon iritis after primary fresh amniotic membrane transplantation.
AB  - PURPOSE: To report the occurrence of hypopyon iritis after primary, fresh
      amniotic membrane transplant (AMT). METHODS: A case report of a 65-year-old man
      who underwent AMT along with placement of hydrophilic contact lens for
      symptomatic relief of pseudophakic bullous keratopathy for the first time. The
      amniotic membrane (AM) transplanted was obtained freshly after an elective
      cesarean section. RESULTS: The patient developed hypopyon on the second
      postoperative day. Culture of remnants of AM and contact lens were negative.
      Hypopyon did not respond to periocular antibiotics but disappeared with
      periocular steroids. Hypopyon was noticed again at 1-week follow-up because of
      poor compliance of the patient. It again responded to periocular steroids. At 1
      year follow-up, the patient is asymptomatic with 20/600 vision. CONCLUSIONS:
      Sterile hypopyon iritis appeared after primary AMT with fresh AM, and it
      disappeared with periocular steroids.

PMID- 18043193
TI  - Corneal bee sting misdiagnosed as viral keratitis.
AB  - PURPOSE: To report a case of chronic keratouveitis caused by a missed bee sting
      injury. METHODS: A 17-year-old boy was referred for management of unresponsive
      viral keratouveitis. Ocular examination revealed corneal edema and scarring,
      atrophic patches on the iris, and anterior polar cataracts. Surprisingly,
      examination also revealed a retained intracorneal bee stinger. A retrospective
      inquiry confirmed a bee sting injury 2 years ago. RESULTS: The patient was
      started on medical treatment and underwent operative removal of the bee stinger.
      Postsurgery, visual acuity improved, and the corneal edema regressed over a 1
      month follow-up. CONCLUSIONS: In cases of chronic keratouveitis, a meticulous
      examination is mandatory to rule out unusual causes like a retained corneal bee
      stinger. A retained intracorneal bee stinger may result in long-term corneal
      inflammation, which may not be controlled adequately with topical steroids. It
      should be removed, irrespective of the duration since the injury.

PMID- 18043194
TI  - Alport syndrome with recurrent herpes simplex virus keratitis.
AB  - PURPOSE: To report a case of Alport syndrome with recurrent herpes simplex virus
      (HSV) keratitis. METHODS: Case report and review of the literature. RESULTS: A 29
      year-old man with Alport syndrome suffered from 4 consecutive episodes of HSV
      keratitis within 2 years. A type IV collagen defect in basement membranes plays
      an important role in the pathogenesis of Alport syndrome. The relationship
      between HSV keratitis and Alport syndrome is discussed. After remission from HSV
      keratitis, the patient underwent bilateral phacoemulsification and posterior
      chamber intraocular lens implantation for anterior lenticonus and an anterior
      polar cataract. After surgery, the uncorrected visual acuity was 20/20 in both
      eyes. CONCLUSIONS: We assume that the underlying basement membrane defects in
      Alport syndrome may account for the recurrent episodes of HSV keratitis in this
      patient. In addition, phacoemulsification and posterior-chamber intraocular lens
      implantation, rather than correction of refractive errors, provide a safe and
      efficient therapeutic choice for the management of anterior lenticonus, with or
      without associated cataract in patients with Alport syndrome.

PMID- 18043195
TI  - Late bacterial keratitis after intracorneal ring segments (Ferrara ring)
      insertion for keratoconus.
AB  - PURPOSE: To report a case of late bacterial keratitis after intrastromal corneal
      ring segments (ICRSs; Ferrara ring; Ferrara Ophthalmics, Belo Horizonte, Brazil).
      METHODS: Review the clinical findings in a 42-year-old woman with bilateral
      keratoconus who underwent implantation of Ferrara ring segments in her left eye
      and 4 months later presented with corneal infiltrates and hypopyon. Bacterial
      staining, culture, and antibiotic sensitivities were done. Medical treatment and
      rings explantation were performed. RESULTS: The cultures revealed growth of
      vancomycin-oxacillin sensible coagulase-positive Staphylococcus aureus. Treatment
      with topical moxifloxacin, topical imipenem, and systemic intravenous and topical
      vancomycin was kept for two weeks. Corneal inflammation and hypopyon resolved,
      leaving a minimal residual leucoma. CONCLUSIONS: Infectious keratitis is an
      uncommon complication of ICRS and it may be late in presentation, even months
      after implantation. Importance of patient education about alarm symptoms and the
      need for long-term close postoperative follow-up cannot be underestimated. If a
      change in surgical technique, i.e., suturing the incision, has an influence in
      this complication's incidence, it will require further studies.

PMID- 18043196
TI  - Focal corneal decompensation after filtering surgery with mitomycin C.
AB  - PURPOSE: To report a case with focal corneal decompensation after filtering
      surgery with inadvertent inadequate irrigation of mitomycin C (MMC). METHODS:
      Case report and review of literature. RESULTS: A 25-year-old man first referred
      with the complaint of photophobia. His ocular examinations revealed diffuse
      keratic precipitates and many iris nodules in both eyes. The primary diagnosis
      was idiopathic bilateral granulomatous anterior uveitis. The intraocular pressure
      (IOP) gradually increased in the left eye and was not controlled with a
      prescription of topical antiglaucoma medications. As the disease progressed, the
      left eye underwent filtering surgery with MMC 0.02%. The postoperative period was
      uneventful, and the anterior chamber was deep after surgery. The IOP was
      controlled without medications; however; the inferior third of the cornea was
      edematous because of severe endothelial dysfunction. CONCLUSIONS: Inadequate
      irrigation of MMC during filtering surgery can cause focal corneal
      decompensation.

PMID- 18043197
TI  - Keratoglobus in association with posterior polymorphous dystrophy.
AB  - PURPOSE: To report a case of a 34-year-old woman presenting with keratoglobus and
      posterior polymorphous corneal dystrophy (PPMD). METHODS: Observational case
      report including ophthalmologic examination, topographic findings, and specular
      microscopy findings. RESULTS: This patient presented with corneal steepening on
      topography consistent with keratoglobus, as well as large areas of irregular
      polymorphous changes of the corneal endothelium on specular microscopy consistent
      with PPMD. CONCLUSIONS: We report the first case with clinical features of both
      keratoglobus and PPMD. This report brings forth the description of keratoglobus
      findings on Orbscan topography.

PMID- 18043198
TI  - Anterior chamber maintenance during descemet stripping.

PMID- 18043199
TI  - Reactivation of recurrent corneal erosion syndrome by continuous positive
      pressure ventilation.

PMID- 18043202
TI  - Mirror, mirror on the wall, which is the fairest meta-analysis of all?

PMID- 18043203
TI  - To use or not to use? Polyclonal intravenous immunoglobulins for the treatment of
      sepsis and septic shock.

PMID- 18043204
TI  - Suppression of monocyte metabolism by septic plasma: revisiting the concept of
      "blood poisoning".

PMID- 18043205
TI  - Sedative effects of Mozart's music in the critically ill: enjoy the hormonal
      symphony.

PMID- 18043206
TI  - The trouble with tubes.

PMID- 18043207
TI  - Constipation: does it increase morbidity and mortality in critically ill
      patients?

PMID- 18043208
TI  - Levosimendan in cardiogenic shock: the magic drug for every patient?

PMID- 18043209
TI  - Clinical use of hydroxyethylstarch: colloidal confusion or clarity?

PMID- 18043210
TI  - Evolving paradigms in acute kidney injury.

PMID- 18043211
TI  - Mechanical vagus nerve stimulation--A new adjunct in sepsis prophylaxis and
      treatment?

PMID- 18043212
TI  - Ultrasound lung comets: a clinically useful sign in acute respiratory distress
      syndrome/acute lung injury.

PMID- 18043213
TI  - How early can we go? Taking hypothermia out of the intensive care unit.

PMID- 18043214
TI  - Sports cars versus freight trains: why infusion performance is in the details.

PMID- 18043215
TI  - A small step forward on a long way to go.

PMID- 18043216
TI  - Gold standard for humidification: heat and moisture exchangers, heated
      humidifiers, or both?

PMID- 18043217
TI  - Separating practice guidelines from pharmaceutical marketing.

PMID- 18043220
TI  - Prolonged mechanical ventilation is even more expensive.

PMID- 18043221
TI  - Agreement with antimicrobial management for pseudomonal ventilator-associated
      pneumonia.

PMID- 18043224
TI  - Gastrointestinal infections, an overview: from pathogens to metagenomes.

PMID- 18043225
TI  - Gastrointestinal microbiology enters the metagenomics era.
AB  - PURPOSE OF REVIEW: Advances in DNA sequence-based technologies now permit genetic
      analysis of complex microbial populations without the need for prior cultivation.
      This review summarizes the molecular methods of culture-independent microbiology
      ('metagenomics') and their recent application to studies of the human
      gastrointestinal tract in both health and disease. RECENT FINDINGS: Culture
      independent metagenomic surveys reveal unprecedented microbial biodiversity in
      the human intestine. Upwards of 40,000 bacterial species are estimated to
      comprise the collective gastrointestinal microbiome, most of which have not been
      characterized by culture. Diverse conditions such as antibiotic-associated
      diarrhea, Crohn's disease, ulcerative colitis, obesity, and pouchitis have been
      correlated with large-scale imbalances in gastrointestinal microbiota, or
      'dysbiosis'. These findings demonstrate the importance of commensal
      microorganisms in maintaining gastrointestinal health. SUMMARY: Through
      technological and conceptual innovations in metagenomics, the complex microbial
      habitat of the human gastrointestinal tract is now amenable to detailed
      ecological analysis. Large-scale shifts in gut commensal populations, rather than
      occurrence of particular microorganisms, are associated with several
      gastroenterological conditions; redress of these imbalances may ameliorate the
      conditions.

PMID- 18043226
TI  - Alterations in intestinal microbial flora and human disease.
AB  - PURPOSE OF REVIEW: To highlight the evidence supporting the role of altered
      commensal gut flora in human disease. While the contribution of the indigenous
      gut microbial community is widely recognized, only recently has there been
      evidence pointing to indigenous flora in disease. RECENT FINDINGS: This review
      discusses recent evidence pointing to the role of altered commensal gut flora in
      such common conditions as irritable bowel syndrome and inflammatory bowel
      disease. Recent studies document the intricate relationship between the vast
      population of microbes that live in our gut and the human host. Since increased
      intestinal permeability and immune activation are consequences of an altered host
      gut microbial relationship, what are the clinical effects of this shift in
      relationship? SUMMARY: We focus on the example of an abnormal expansion of gut
      microbial flora into the small bowel or small intestinal bacterial overgrowth and
      discuss the effects of bacterial overgrowth on the human host in acute
      pancreatitis, bacterial gastroenteritis, irritable bowel syndrome, inflammatory
      bowel disease, hepatic encephalopathy, and fibromyalgia and burn injury. The
      identification of the underlying role of altered commensal gut microbiota in
      these and other human diseases could lead to novel diagnostic and therapeutic
      strategies that would improve clinical outcome.

PMID- 18043227
TI  - The evidence for Mycobacterium paratuberculosis in Crohn's disease.
AB  - PURPOSE OF REVIEW: Though long hypothesized, the putative link between
      Mycobacterium avium paratuberculosis and Crohn's disease remains neither
      confirmed nor refuted. This article reviews published contributions that directly
      or indirectly address this question. RECENT FINDINGS: Epidemiologic studies,
      looking for M. avium paratuberculosis DNA in Crohn's tissue, show a strong
      association between the agent and this disease. Supporting data, however, are
      presently inconclusive on a causal role. Genetic studies provide indirect support
      for a role of mycobacteria in Crohn's disease, by identifying susceptibility
      genes that encode proteins implicated in innate immunity to intracellular
      bacteria. Clinical trial data support at least a short-term benefit for
      antimycobacterial therapy in Crohn's disease, but the microbial specificity of
      this response is presently unknown. SUMMARY: There appears to be a strong
      association between M. avium paratuberculosis and Crohn's disease, but the
      causality of this association is unknown. Consequently, the therapeutic
      implications of this association require further study. A number of critical
      questions about the biology of M. avium paratuberculosis remain unanswered. Data
      from studies of this organism, and its interaction with the immune system, can
      help address proposed reasons for or against a role of M. avium paratuberculosis
      in the etiology of Crohn's disease.

PMID- 18043228
TI  - Pathogenesis of enteric Salmonella infections.
AB  - PURPOSE OF REVIEW: Gastrointestinal disease caused by Salmonella species leads to
      significant morbidity and mortality worldwide. The use of various animal models
      has greatly advanced understanding of Salmonella pathogenesis at intestinal and
      systemic sites. This review will emphasize recent advances in the understanding
      of intestinal Salmonella infections. RECENT FINDINGS: Recent research has focused
      on bacterial products and the host pathogen recognition receptors involved in the
      activation of immune pathways. In particular, activation of Toll-like receptor 5
      and Ipaf by Salmonella flagellin has been a major finding. The discovery of
      cryptopatches as novel lymphoid follicles and the characterization of intestinal
      dendritic cell populations have been examined in the context of Salmonella
      infections. The development and use of the streptomycin pretreated mouse model of
      enterocolitis has allowed researchers to probe the host factors contributing to
      intestinal immunopathology. Furthermore, the analysis of microbiota in Salmonella
      infections has provided new insights regarding the role of inflammation in
      gastrointestinal diseases. In addition, the contributions of specific Salmonella
      type 3-secreted effectors to the establishment and modulation of inflammation
      have been further refined. SUMMARY: New advances in animal models have allowed
      researchers to further define the contribution of specific bacterial and host
      factors involved in Salmonella-induced enterocolitis.

PMID- 18043229
TI  - Pathogenesis of Campylobacter.
AB  - PURPOSE OF REVIEW: Molecular pathogenesis of Campylobacter jejuni has lagged
      behind that of other enteric pathogens. This review summarizes advances in the
      biology and pathogenesis of C. jejuni. RECENT FINDINGS: Multiple genome sequences
      have defined conserved and hypervariable loci in the C. jejuni genome.
      Interaction of C. jejuni with eukaryotic cells results in numerous signal
      transduction changes and release of proinflammatory cytokines. In-vivo models
      based on immune knockout mice have also revealed new information on pathogenesis.
      SUMMARY: New information and new methods are available that should provide
      important tools to further understand pathogenesis of this elusive pathogen.

PMID- 18043230
TI  - Utility of the Citrobacter rodentium infection model in laboratory mice.
AB  - PURPOSE OF REVIEW: There have been considerable advances in our understanding of
      the molecular pathogenesis of enteropathogenic Escherichia coli and
      enterohemorrhagic E. coli infection. Given the difficulty of infecting laboratory
      mice with these diarrhea-causing pathogens, a growing number of studies have
      found the murine bacterial pathogen Citrobacter rodentium to provide a robust,
      relevant in-vivo model system. RECENT FINDINGS: All inbred strains and outbred
      stocks of laboratory mice studied to date have been found to be susceptible to C.
      rodentium infection. The natural course of disease ranges from subclinical
      epithelial hyperplasia in the colon, to clinical diarrhea and colitis, to fatal
      infection, depending on the age, genetic background, and health status of the
      host. Infection is self-limiting, leading to disease resolution and protective
      immunity. Here we review recent discoveries related to bacterial virulence
      determinants, epithelial hyperplasia, innate and adaptive immune responses, and
      mechanisms of diarrhea. SUMMARY: Infection of laboratory mice with C. rodentium
      provides a useful in-vivo model for studying the pathogenesis of infectious
      gastroenteritis and acute diarrheal illness, and for preclinical evaluation of
      candidate preventive and therapeutic agents.

PMID- 18043231
TI  - Pathogenesis and treatment of Shiga toxin-producing Escherichia coli infections.
AB  - PURPOSE OF REVIEW: Shiga toxin-producing Escherichia coli cause hemorrhagic
      colitis and hemolytic uremic syndrome. We will summarize the literature on
      incidence and outcomes of these infections, and then review the pathogenesis to
      explain the current recommendations against antibiotic use and to suggest
      alternative therapies. RECENT FINDINGS: Shiga toxin-producing E. coli continue to
      be prevalent in the industrialized world because of dissemination in food
      products contaminated by ruminant feces. Declines in ground beef-related
      outbreaks have been matched by increased cases related to green vegetables.
      Fifteen percent of patients infected with E. coli O157:H7 progress to hemolytic
      uremic syndrome, but this figure may reach 50% if antibiotics are used.
      Mechanisms for bacteriophage induction causing Shiga toxin production, and for
      Shiga toxin dissemination to endothelium in gut, kidney and brain, may explain
      the negative effects of antibiotics and lead to rational therapies. Shiga toxin
      binders were not effective in clinical trials, but more avid binding agents may
      be. Current treatment recommendations are to maintain hydration to prevent
      thrombotic complications. Human vaccines are unlikely to be utilized. Cattle
      vaccines may prove the most significant approach to this disease. SUMMARY:
      Improved understanding of Shiga toxin-producing Escherichia coli pathophysiology
      and progression to hemolytic uremic syndrome provides the basis for prevention,
      prophylactic and treatment strategies.

PMID- 18043232
TI  - Chemoprevention of colorectal cancer: why all the confusion?
AB  - PURPOSE OF REVIEW: Chemoprevention provides an opportunity to complement
      screening for the prevention of colorectal neoplasia. Findings from prospective
      randomized trials often conflict with those of observational studies. This review
      discusses some of the possible reasons based on recent clinical trials. RECENT
      FINDINGS: A recent prospective randomized trial demonstrates that folic acid
      supplementation in patients with a previous history of colorectal adenomas does
      not reduce future colorectal adenoma risk, and may possibly increase the risk of
      colorectal neoplasia. SUMMARY: The results of prospective randomized human trials
      of chemopreventive agents have in many cases been less impressive or have
      conflicted with the results of observational studies. Issues to be considered are
      the timing of the intervention during multistep carcinogenesis, baseline levels
      in a given individual or population, the complexity of dietary interactions, dose
      response effects, and the duration of study.

PMID- 18043233
TI  - Nutrition and colonic health: the critical role of the microbiota.
AB  - PURPOSE OF REVIEW: To highlight mechanisms whereby diet affects colonic function
      and disease patterns. RECENT FINDINGS: Topical nutrients are preferentially used
      by the gut mucosa to maintain structure and function. With the colon, topical
      nutrients are generated by the colonic microbiota to maintain mucosal health.
      Most importantly, short chain fatty acids control proliferation and
      differentiation, thereby reducing colon cancer risk. In patients with massive
      loss of small intestine, short chain fatty acid production supports survival by
      releasing up to 1000 kcal energy/day. Human studies show that the microbiota
      synthesizes a large pool of utilizable folate which may support survival in
      impoverished populations. Unfortunately, the microbiota may also elaborate toxic
      products from food residues such as genotoxic hydrogen sulfide by sulfur-reducing
      bacteria in response to a high-meat diet. The employment of culture-free
      techniques based on 16S regions of DNA has revealed that our colons harbor over
      800 bacterial species and 7000 different strains. Evidence suggests that the diet
      directly influences the diversity of the microbiota, providing the link between
      diet, colonic disease, and colon cancer. The microbiota, however, can determine
      the efficiency of food absorption and risk of obesity. SUMMARY: Our
      investigations have focused on a small number of bacterial species:
      characterization of microbiota and its metabolism can be expected to provide the
      key to colonic health and disease.

PMID- 18043234
TI  - Stem cells as common ancestors in a colorectal cancer ancestral tree.
AB  - PURPOSE OF REVIEW: Cancer is thought to be an evolutionary process. Modern
      studies of evolution increasingly rely on genome comparisons, and similar
      molecular phylogeny approaches could be translated to somatic cell genomes to
      reconstruct colorectal cancer progression. The purpose of this review is to
      outline how human somatic cell ancestral trees can organize many old and new
      observations. RECENT FINDINGS: A somatic cell tree starts from the zygote and
      ends with present day normal or neoplastic cells. In between are ancestors and
      dead ends, which functionally correspond to stem and nonstem cells. Cancer genome
      projects illustrate that mutations are relatively infrequent, and consistent with
      normal mutation rates, particularly if mutations begin to accumulate from birth.
      Therefore, some mutations eventually found in cancers may first occur in normal
      appearing crypts, which are maintained by niches that allow for stem cell clonal
      evolution and selection. Although mutations occur too infrequently to function as
      somatic cell molecular clocks, potentially more labile epigenetic changes in CpG
      methylation may also record somatic cell ancestry. SUMMARY: Somatic cell
      evolution can occur throughout life, and potentially at least some of this unseen
      past may be reconstructed by 'reading' the lifetime changes that accumulate
      within our genomes.

PMID- 18043235
TI  - Endoscopic imaging: emerging optical techniques for the detection of colorectal
      neoplasia.
AB  - PURPOSE OF REVIEW: Advances in bioengineering have spawned various imaging
      modalities which have revolutionized endoscopy. Some of these technologies
      provide real-time, high-resolution, subcellular imaging. This review provides an
      update on these technologies and their role in the evaluation of colorectal
      neoplasia. RECENT FINDINGS: Narrow band imaging has been shown to visualize
      capillary patterns in early cancer and is complementary to magnification
      endoscopy. Optical coherence tomography has been used to evaluate neoplastic
      progression and distinguish Crohn's from ulcerative colitis. Confocal
      endomicroscopy has been shown to accurately predict neoplastic changes in polyps
      and identify areas of neoplasia in patients with colitis. Among the spectroscopic
      techniques, autofluorescence is best studied in the colon and has been used to
      identify adenomas and dysplasia in inflammatory bowel disease. Endocytoscopy is a
      relatively new technology but shows promise in distinguishing neoplastic lesions.
      SUMMARY: Recently a number of imaging technologies have arisen that have the
      potential to enhance our detection of colorectal neoplasia. Several of these,
      such as autofluorescent imaging and narrow band imaging, are 'red flag'
      techniques which enhance our visualization of mucosal change(s). Complementary
      technologies, such as confocal endomicroscopy and endocytoscopy, provide
      subcellular imaging. Combined with a 'red flag' technique, these may transform
      our approach to colonoscopy, allowing the real-time detection and diagnosis of
      neoplasia.

PMID- 18043236
TI  - Pouch-ouch.
AB  - PURPOSE OF REVIEW: For patients who require colectomy, the ileal pouch anal
      anastomosis operation has alleviated the need for permanent ileostomy and has
      improved associated self-esteem issues. The most common complication of this
      surgery, however, is pouchitis. This review highlights the most recent research
      in the pathophysiology, risk factors, diagnosis and management of pouchitis, and
      pouch surveillance for neoplasia in patients who had ulcerative colitis. RECENT
      FINDINGS: Markers of inflammation, including fecal lactoferrin and mucosal
      cytokines, have been reported as useful in differentiating between irritable
      pouch syndrome and pouchitis. Numerous risk factors for the development of
      pouchitis have been identified. They include the presence of perinuclear
      antinuclear cytoplasmic antibodies, steroid use prior to colectomy, dysplasia as
      the indication for colectomy, the presence of extraintestinal manifestations, and
      an elevated platelet count. Therapy for acute pouchitis remains a short course of
      antibiotics. For chronic pouchitis, studies found success with rifaximin,
      tinidazole, and oral budesonide. Cancer in the residual rectal mucosa, in the
      ileal mucosa, and in pouch polyps occurs frequently enough to warrant
      surveillance. SUMMARY: Risk factors for the development of pouchitis should be
      discussed with patients. Less invasive diagnostic strategies have been proposed
      and antibiotics are still the mainstay of therapy.

PMID- 18043237
TI  - Bibliography. Current world literature. Gastrointestinal infections.

PMID- 18043239
TI  - Severe congenital neutropenia and the unfolded protein response.
AB  - PURPOSE OF REVIEW: Severe congenital neutropenia is an inborn disorder of
      granulopoiesis. Mutations of ELA2, encoding neutrophil elastase, are present in
      approximately 50% of cases of severe congenital neutropenia and nearly all cases
      of cyclic neutropenia, a related disorder of granulopoiesis. Herein, we review
      recent studies of the molecular pathogenesis of severe congenital neutropenia,
      with an emphasis on those cases associated with mutations of ELA2. RECENT
      FINDINGS: Genetic evidence suggests that ELA2 mutations act in a dominant, cell
      intrinsic fashion to disrupt granulopoiesis. A unifying model that accounts for
      the different clinical phenotypes (severe congenital neutropenia versus cyclic
      neutropenia) and the diversity of ELA2 mutations (over 50 have been identified),
      however, is lacking. Recent studies suggest that mutations of ELA2 may cause
      disease through induction of the unfolded protein response. In this model, the
      ELA2 mutations result in the production of misfolded neutrophil elastase protein,
      activation of the unfolded protein response, and ultimately apoptosis of
      granulocytic precursors. The propensity of individual neutrophil elastase mutants
      to misfold may determine the magnitude of unfolded protein response-induced
      apoptosis and ultimately the clinical phenotype. SUMMARY: Recent studies provide
      support for a unfolded protein response model of disease pathogenesis in cases of
      severe congenital neutropenia associated with ELA2 mutations and place severe
      congenital neutropenia in a growing list of human disease caused by misfolded
      proteins.

PMID- 18043240
TI  - Chronic idiopathic neutropenias and severe congenital neutropenia.
AB  - PURPOSE OF REVIEW: Chronic idiopathic and severe congenital neutropenias are rare
      disorders for which recent discoveries have highlighted mechanisms and
      consequences. RECENT FINDINGS: An inflammatory bone marrow milieu has been shown
      to be a major contributor to the pathophysiology of chronic idiopathic
      neutropenia. Activated T-lymphocytes with myelosuppressive properties and pro
      apoptotic mediators, such as IFNgamma, TNFalpha, Fas-ligand and TGFbeta1 result
      in accelerated apoptosis of granulocytic progenitor cells. Decreased levels of
      the anti-inflammatory cytokine IL-10 further disturb the balance between survival
      and pro-apoptotic mediators in chronic idiopathic neutropenia. Mutations in the
      HAX1 gene are associated with most cases of recessive autosomal severe congenital
      neutropenia, while ELA2 mutations are found in most cases of autosomal dominant
      and sporadic cases. The role of HAX-1 protein as a regulatory step in apoptosis
      provides further evidence for severe congenital neutropenia as a disorder of
      programmed cell death. The preleukemic character of severe congenital
      neutropenia, particularly for patients with need for high granulocyte colony
      stimulating factor dosage, was recently emphasized. SUMMARY: Chronic idiopathic
      (or as recent data suggest, immunologic) and severe congenital neutropenias
      provide intriguing models for better understanding of regulation of myelopoiesis.
      Similarities and differences between the two disorders might help to dissect
      these regulatory events.

PMID- 18043241
TI  - Idiosyncratic drug-induced agranulocytosis or acute neutropenia.
AB  - PURPOSE OF REVIEW: Idiosyncratic drug-induced agranulocytosis or acute
      neutropenia is an adverse event resulting in a neutrophil count of under 0.5 x
      10/l. Patients with such severe neutropenia are likely to experience life
      threatening and sometimes fatal infections. RECENT FINDINGS: Over the last 20
      years, the incidence of idiosyncratic drug-induced agranulocytosis or acute
      neutropenia has remained stable at 2.4-15.4 cases per million, despite the
      emergence of new causative drugs: antibiotics (beta-lactam and cotrimoxazole),
      antiplatelet agents (ticlopidine), antithyroid drugs, sulfasalazine, neuroleptics
      (clozapine), antiepileptic agents (carbamazepine), nonsteroidal anti-inflammatory
      agents and dipyrone. Drug-induced agranulocytosis remains a serious adverse event
      due to the occurrence of severe sepsis with severe deep infections (such as
      pneumonia), septicemia and septic shock in around two thirds of patients. In this
      setting, old age (>65 years), septicemia or shock, metabolic disorders such as
      renal failure, and a neutrophil count under 0.1 x 10/l are poor prognostic
      factors. Nevertheless with appropriate management using preestablished
      procedures, with intravenous broad-spectrum antibiotic therapy and hematopoietic
      growth factors, the mortality rate is currently around 5%. SUMMARY: Given the
      increased life expectancy and subsequent longer exposure to drugs, as well as the
      development of new agents, healthcare professionals should be aware of this
      adverse event and its management.

PMID- 18043242
TI  - Chediak-Higashi syndrome.
AB  - PURPOSE OF REVIEW: Chediak-Higashi syndrome, a rare autosomal recessive disorder,
      was described over 50 years ago. Patients show hypopigmentation, recurrent
      infections, mild coagulation defects and varying neurologic problems. Treatment
      is bone marrow transplant, which is effective in treating the hematologic and
      immune defects, however the neurologic problems persist. The CHS1/LYST gene was
      identified over 10 years ago and homologous CHS1/LYST genes are present in all
      eukaryotes. This review will discuss the advances made in understanding the
      clinical aspects of the syndrome and the function of CHS1/LYST/Beige. RECENT
      FINDINGS: Clinical reports of Chediak-Higashi syndrome have identified mutations
      throughout the CHS1/LYST gene. The nature of the mutation can be a predictor of
      the severity of the disease. Over the past decade the CHS1/LYST family of
      proteins has been analyzed using model organisms, two-hybrid analysis,
      overexpression phenotypes and dominant negatives. These studies suggest that the
      CHS1/LYST protein is involved in either vesicle fusion or fission. SUMMARY:
      Although CHS is a rare disease, the Chediak-like family of proteins is providing
      insight into the regulation of vesicle trafficking. Understanding the basic
      mechanisms that govern vesicle trafficking will provide essential information
      regarding how loss of CHS1/LYST affects hematologic, immunologic and neurologic
      processes.

PMID- 18043243
TI  - Wiskott-Aldrich syndrome.
AB  - PURPOSE OF REVIEW: Wiskott-Aldrich syndrome is caused by mutations of the Wiskott
      Aldrich syndrome protein gene, which codes for a cytoplasmic protein with
      multiple functions. This review will focus on recent progress in understanding
      the molecular basis of Wiskott-Aldrich syndrome and its ramifications for the
      cure of this lethal disease. RECENT FINDINGS: The discovery of the causative gene
      has revealed a spectrum of clinical phenotypes demonstrating a strong
      genotype/phenotype correlation. The discovery of unique functional domains of
      Wiskott-Aldrich syndrome protein has been instrumental in defining mechanisms
      that control activation of Wiskott-Aldrich syndrome protein. Long-term follow up
      of patients undergoing hematopoietic stem cell transplantation has led to
      important modifications of the procedure. Studies of Wiskott-Aldrich syndrome
      protein-deficient cell lines and wasp-knockout mice have paved the way for
      possible gene therapy. SUMMARY: Wiskott-Aldrich syndrome protein gene mutations
      result in four clinical phenotypes: classic Wiskott-Aldrich syndrome and X-linked
      thrombocytopenia, intermittent thrombocytopenia and neutropenia. Wiskott-Aldrich
      syndrome protein is a signaling molecule and instrumental for cognate and innate
      immunity, cell motility and protection against autoimmune disease. The success of
      hematopoietic stem cell transplantation is related to the recipient's age, donor
      selection, the conditioning regimen and the extent of reconstitution. Since
      Wiskott-Aldrich syndrome protein is expressed exclusively in hematopoietic stem
      cells, and because Wiskott-Aldrich syndrome protein exerts a strong selective
      pressure, gene therapy is expected to cure the disease.

PMID- 18043244
TI  - Retinoic acid signaling in myelopoiesis.
AB  - PURPOSE OF REVIEW: For decades, retinoic acid has been known to alter the
      proliferation and differentiation of myeloid cells. Currently, retinoic acid is a
      front-line agent in the treatment of certain forms of acute myelogenous leukemia.
      In this review, we focus on recent advances in our understanding of the
      mechanisms by which retinoids affect growth and proliferation of myeloid cells
      and contribute to the pathogenesis of leukemia. We have not attempted to
      summarize the related clinical literature. RECENT FINDINGS: The past 2 years have
      yielded important understanding of the mechanisms by which retinoids and their
      nuclear receptors interact with other signal transduction pathways and
      transcription factors to modify chromatin, alter gene expression, and participate
      in normal myeloid differentiation and leukemogenesis. Important advances
      regarding cell biology, molecular biology, biochemistry, and animal studies of
      retinoids and myeloid differentiation are reviewed. SUMMARY: Greater
      understanding of the role of retinoids and their receptors in myeloid cell growth
      and differentiation provides important insight into normal myelopoiesis. These
      findings have resulted in successful rational approaches to the treatment of
      acute leukemia and provide the promise of improved treatments in the near future.

PMID- 18043245
TI  - Tumor-necrosis-factor-related apoptosis-inducing ligand and the regulation of
      hematopoiesis.
AB  - PURPOSE OF REVIEW: This review will focus on the emerging role of tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL)/TRAIL-receptors in the
      pathophysiology of hematopoiesis and on the potential therapeutic applications of
      either recombinant TRAIL or anti-TRAIL-R1/-R2 agonistic antibodies for the
      treatment of hematological malignancies. RECENT FINDINGS: While CD34
      stem/progenitor cells do not express TRAIL-receptors and are protected from TRAIL
      induced apoptosis, accumulating evidence points to a role for elevated
      expression/release of TRAIL at the bone marrow level in the pathophysiology of
      aplastic anemia, Fanconi anemia, and myelodysplastic syndromes. In-vitro data
      show promising synergistic effects of recombinant TRAIL in association with
      proteasome or histone deacetylase inhibitors, natural compounds or small
      molecules in the therapy of myeloid and lymphoid malignancies. Moreover, although
      both recombinant TRAIL and anti-TRAIL-R1/-R2 antibodies are well tolerated in
      vivo, anti-TRAIL-R1/-R2 agonistic antibodies show the potential advantage of
      avoiding the neutralizing activity of the soluble receptor osteoprotegerin.
      SUMMARY: While a chronic pathological elevation of TRAIL at the bone marrow level
      might contribute to the impairment of normal hematopoiesis, the use of
      recombinant TRAIL and anti-TRAIL-R1/-R2 agonistic antibodies appears particularly
      promising for the treatment of hematological malignancies in particular, of
      multiple myeloma, especially if used in association with innovative therapeutic
      compounds.

PMID- 18043246
TI  - Chemokines in hematopoiesis.
AB  - PURPOSE OF REVIEW: Understanding the regulation of hematopoiesis is important for
      enhanced efficacy of hematopoietic stem and progenitor cell transplantation.
      Chemokines influence migration, survival, and other actions of hematopoietic stem
      and progenitor cells. This article summarizes recent progress in understanding
      the production and actions of chemokines and chemokine receptors, with an
      emphasis on the SDF-1/CXCL12-CXCR4 axis. RECENT FINDINGS: The literature from
      2006 to the present is replete with information on SDF-1/CXCL12 activity,
      including induced intracellular signaling in hematopoietic progenitor cells,
      lymphocytes, other innate immune cells, breast cancer, and other tumor cells, and
      on production of SDF-1/CXCL12, and CXCR4, as well as on actions/production of
      other chemokines. Studies describing these intense research areas are discussed.
      SUMMARY: Chemokine-chemokine receptor interactions are important to hematopoiesis
      and immune cell function, two highly interactive processes. Recent studies have
      clarified the role of chemokines and their receptors in regulating hematopoiesis,
      and agents modulating chemokines are being evaluated in preclinical and clinical
      studies. Examples of such efforts include inhibition of CD26 for enhanced homing
      and engraftment of hematopoietic stem and progenitor cells, and the use of the
      SDF-1/CXCL12-CXCR4 antagonist, AMD3100 for mobilization of hematopoietic stem and
      progenitor cells and their use for stem cell transplantation.

PMID- 18043248
TI  - Bibliography. Current world literature. Myeloid biology.

PMID- 18043247
TI  - Basophils and type 2 immunity.
AB  - PURPOSE OF REVIEW: Mechanisms involved in the development of in-vivo type 2
      immunity are poorly defined. Basophils are potent IL-4-producing cells and may
      contribute to the process of polarizing immune responses. RECENT FINDINGS:
      Although basophils represent fewer than 0.5% of blood leukocytes, their frequency
      dramatically increases under certain circumstances, particularly Th2-related
      responses including parasitic infection and allergic inflammation. Recent studies
      proposed the hypothesis that basophils could contribute to the development of
      type 2 immunity by providing initial IL-4 important in T cell polarization and by
      recruiting other effector cells such as eosinophils or neutrophils. Multiple
      stimuli of IgE-dependent and IgE-independent pathways that lead to release of
      cytokines and mediators from activated basophils have been identified. In
      addition, progenitors that differentiate into mature basophils have recently been
      identified. SUMMARY: The current review revisits basophils with the goal of
      providing insights into understanding unappreciated roles of basophils in vivo.

PMID- 18043250
TI  - Neuroendocrine tumors of the diffuse neuroendocrine system.
AB  - PURPOSE OF REVIEW: Neuroendocrine tumors (previously referred to as carcinoids)
      are ill-understood, enigmatic malignancies that, although slow-growing compared
      with adenocarcinomas, can behave aggressively. In 2004, they comprised 1.25% of
      all malignancies; their incidence is increasing by approximately 6% per year. The
      present review provides an overview on neuroendocrine tumors and focuses on
      general features and current diagnostic and therapeutic options. RECENT FINDINGS:
      Neuroendocrine tumors may present a considerable diagnostic and therapeutic
      challenge as their clinical presentation is nonspecific and usually late, when
      metastases are already evident. Topographic localization is by computed
      tomography, magnetic resonance imaging, somatostatin receptor scintigraphy, whole
      body positron emission tomography or endoscopy/ultrasound. Bronchoscopy is useful
      to verify the diagnosis when lesions are located centrally in the bronchi. No
      curative treatment except for radical surgery (almost never feasible) exists.
      Palliative and symptomatic treatment is based on surgical debulking, tumor
      embolization, and biotherapy with somatostatin analogues. Chemotherapy and
      radiotherapy are usually ineffective, but novel drugs such as tyrosine kinase
      receptor inhibitors show promising results in phase II clinical studies. SUMMARY:
      Tumors of the diffuse neuroendocrine system represent a significant and
      increasing clinical problem, and there is a need to develop both early diagnostic
      tests as well as to establish targeted therapeutic strategies.

PMID- 18043251
TI  - Recent developments in the clinical application of thyroid cancer biomarkers.
AB  - PURPOSE OF REVIEW: The aim of this article is to provide an update on the status
      of the clinical application of thyroid cancer biomarkers. RECENT FINDINGS: Our
      understanding of the tumor cell biology of thyroid cancer of follicular cell
      origin has improved and modern genomic technological tools are providing new data
      that may have clinical ramifications. The common somatic genetic changes in
      thyroid cancer of follicular cell origin (RET/PTC, NTRK, RAS, BRAF, PAX8
      PPARgamma) are generally mutually exclusive, with distinct genotype-histologic
      subtype of thyroid cancer and genotype-phenotype associations observed. Mutation
      analysis in thyroid nodule fine needle aspiration biopsy has been applied to
      improve the diagnostic accuracy of fine needle aspiration biopsy and cytologic
      examination. Gene expression profiling studies have identified numerous
      diagnostic biomarkers of thyroid cancer that are beginning to be applied in fine
      needle aspiration biopsy samples to improve diagnosis. The BRAF mutation has
      recently been shown to be associated with disease aggressiveness, and as an
      independent prognostic biomarker. SUMMARY: There has been significant progress
      toward identifying biomarkers that could improve the accuracy of fine needle
      aspiration biopsy in the evaluation of patients with thyroid nodule and
      predicting disease aggressiveness. Future clinical trials evaluating the accuracy
      and cost-effectiveness of applying these biomarkers in the management of thyroid
      neoplasm should be considered.

PMID- 18043252
TI  - Novel chemotherapy options for advanced thyroid tumors: small molecules offer
      great hope.
AB  - PURPOSE OF REVIEW: Endocrine tumors are often overlooked in medical oncology
      discussions, as many of them are effectively cured by surgery alone or surgery
      plus an ablative radiation therapy. For the rare aggressive endocrine cancers
      that are widely metastatic or rapidly progressive, however, the role of the
      medical oncologist becomes more important. To date, conventional chemotherapy has
      not had a significant impact on the natural history of these malignancies. This
      has led to the evaluation of novel compounds; some of which have already entered
      into randomized clinical trials. This review will focus on the advances made in
      the treatment of advanced thyroid cancer, the commonest of endocrine
      malignancies. RECENT FINDINGS: A growing understanding of molecular oncology has
      allowed the development of targeted agents in different types of thyroid cancer.
      Some agents presently being evaluated in clinical trials include inhibitors of
      angiogenesis (sorafenib, CA4P, axitinib and vandetanib), the epidermal growth
      factor receptor (gefitinib, vandetanib) and RET protein (vandetanib). Preliminary
      results from these studies will be reviewed in this paper. SUMMARY: The recent
      explosion of targeted agents available for study has generated enthusiasm for
      oncologists treating thyroid cancer. Antiangiogenesis strategies in particular
      appear promising. RET inhibition in medullary thyroid cancer is also being
      explored. Further clinical trials will determine which of these will enter the
      clinic in the near future.

PMID- 18043253
TI  - Sporadically occurring functional pancreatic endocrine tumors: review of recent
      literature.
AB  - PURPOSE OF REVIEW: Pancreatic neuroendocrine tumors are rare neoplasms often
      associated with a clinical syndrome. Their rarity makes a comprehensive study
      difficult at any single institution, while their uniqueness makes them desirable
      for investigation. This review summarizes recent information and advancements
      concerning pancreatic neuroendocrine tumor diagnosis, imaging characteristics,
      treatment algorithms, and staging. RECENT FINDINGS: Insulinomas and gastrinomas
      comprise the majority of functional pancreatic neuroendocrine tumors. Advances in
      their identification and diagnostic evaluation, imaging techniques, and treatment
      algorithms are presented. Furthermore, a new staging classification system has
      been proposed which may significantly improve the ability to conduct future multi
      institutional investigations on pancreatic neuroendocrine tumors. SUMMARY:
      Although rare, a thorough understanding of pancreatic neuroendocrine tumors is
      essential for all physicians due to the wide variety of symptoms with which
      patients present. Currently, patients are often misdiagnosed for extended periods
      of time. This review summarizes the recently published literature about
      diagnosis, imaging, treatment, and staging of pancreatic neuroendocrine tumors.

PMID- 18043254
TI  - Current management of adrenal tumors.
AB  - PURPOSE OF REVIEW: Adrenal tumors evoke considerable interest and diagnostic
      challenges. This rare group of tumors includes functional tumors with a gamut of
      clinical presentations, as well as adrenocortical carcinoma, with its advanced
      disease at presentation and dismal prognosis posing additional challenge.
      Increasing detection of incidentalomas adds further interest with the concomitant
      diagnostic and management dilemmas. RECENT FINDINGS: Significant advances have
      been made in diagnostic imaging modalities for identifying malignancy risk in
      adrenal incidentalomas. Considerable progress has occurred in understanding
      adrenocortical carcinoma pathogenesis from the study of genetics at the germline
      level in familial carcinomas, as well as at the somatic level by analyzing
      molecular alterations in sporadic tumors; this research supplies opportunities to
      develop novel therapeutic agents against a tumor with poor prognosis. SUMMARY:
      Laparoscopic adrenalectomy has emerged as standard of care in the treatment of
      functional benign adenomas and nonfunctional tumors larger than 4 cm when
      adrenocortical carcinoma is not suspected. Open adrenalectomy with en-bloc
      excision has been the mainstay for primary and recurrent adrenocortical carcinoma
      due to the lack of effective adjuvant therapy. International consensus
      conferences have attempted to standardize diagnostic and treatment approaches in
      the management of adrenal tumors; further research is necessary.

PMID- 18043255
TI  - Health services research in endocrine surgery.
AB  - PURPOSE OF REVIEW: We review recent health services research studies examining
      clinical and economic outcomes in endocrine surgery. RECENT FINDINGS: Recent
      studies have focused on such important issues as the use of the Internet in
      medicine, patient quality of life, cost-effectiveness of emerging surgical
      technologies, and labor-force modeling. There is a need for accurate and
      informative websites dedicated to thyroid disease, given the large number of
      patients who use the Internet for healthcare information. Debate continues about
      the relative merits of medical and surgical therapy for primary
      hyperparathyroidism; based on measurements of quality of life and cost
      effectiveness, parathyroidectomy appears to be favored. Surgical outcomes studies
      have shown parathyroidectomy to be safe in octogenarian and nonagenarian patients
      with primary hyperparathyroidism. Sophisticated work-force projections suggest
      that the supply of endocrine surgeons will grow over the next 15 years, but will
      be outpaced by the anticipated demand. SUMMARY: Health services research is a
      burgeoning field of investigation in endocrine surgery. It needs to be developed
      to improve the quality of care of patients with thyroid, parathyroid, adrenal and
      endocrine pancreatic diseases.

PMID- 18043256
TI  - Primary hyperparathyroidism.
AB  - PURPOSE OF REVIEW: This article reviews the diagnosis and treatment of primary
      hyperparathyroidism, including recent literature on the subject. RECENT FINDINGS:
      Important recent advancements in the field of parathyroid disease include
      improvements in preoperative localization, the use of intraoperative parathyroid
      hormone monitoring, and the development of minimally invasive and videoscopic
      surgical techniques. Additionally, there has been significant interest in better
      understanding the clinical changes and presentation of sporadic primary
      hyperparathyroidism, including the assessment of neurocognitive symptoms before
      and after surgery. This has led to a change in the definition of the
      'asymptomatic patient' and altered the criteria used to trigger surgical
      intervention. SUMMARY: Although the cause of primary hyperparathyroidism is still
      poorly understood, surgical parathyroidectomy results in long-term cure in
      greater than 95% of cases. Improvements in our understanding of this disease
      continue to make diagnosis and treatment safer and more effective.

PMID- 18043257
TI  - Differentiated thyroid cancer in children: diagnosis and management.
AB  - PURPOSE OF REVIEW: Differentiated thyroid cancer is the most common endocrine
      malignancy in children. In 2006, the American Thyroid Association Guidelines
      Taskforce released detailed management recommendations for differentiated thyroid
      cancer, which primarily addressed the approach for treating adult patients.
      Children with differentiated thyroid cancer present with more advanced disease
      and yet have a more favorable outcome than adults. Thus optimal treatment for
      younger patients with differentiated thyroid cancer may differ from that for
      adults. RECENT FINDINGS: All available data regarding differentiated thyroid
      cancer treatment in children are retrospective. In the past year, several large
      case series have been published that strengthen the argument for total
      thyroidectomy at the time of diagnosis, followed by administration of radioactive
      iodine for remnant ablation. There have also been recent advances in
      understanding the genetic abnormalities associated with pediatric thyroid cancer.
      SUMMARY: The optimal treatment of differentiated thyroid cancer in pediatric
      patients continues to be debated. Recent publications from institutions around
      the world provide useful data regarding current approaches to this unusual
      disease. Further collaborative studies are needed to further refine the surgical
      approach, particularly the extent of lymph-node dissection, radioactive iodine
      dosing, and the role of genetic analysis in diagnosis and clinical approach.

PMID- 18043258
TI  - Systematic analyses of the cancer genome: lessons learned from sequencing most of
      the annotated human protein-coding genes.
AB  - PURPOSE OF REVIEW: The availability of a reference human genome sequence has
      enabled unbiased mutational analyses of tumor genomes to identify the mutated
      genes that cause cancer. This review discusses recent insights from such analyses
      of protein-coding genes in breast and colorectal cancers. RECENT FINDINGS:
      Mutational analyses of approximately 18,000 human protein-coding genes in breast
      and colorectal cancers have identified 280 candidate cancer genes. These include
      known cancer genes, but most had not previously been linked to cancer. There are
      few frequently mutated cancer genes among hundreds of less frequently mutated
      candidate cancer genes, and the compendium of mutated genes differs among tumors
      of the same tissue origin. SUMMARY: Recent work has shown the feasibility of
      coding cancer genome sequencing, and new technologies promise to facilitate these
      mutational analyses. Whereas cancer genetics can identify candidate genes in a
      rapid and scalable fashion, careful functional studies of mutated genes are
      required for ultimate proof of cancer gene status and translation into clinical
      utility. The rapid progress of cancer genetics has yielded novel diagnostic and
      therapeutic modalities, and cancer genome sequencing will accelerate this
      development to the benefit of cancer patients.

PMID- 18043259
TI  - Integrative oncogenomic approaches for accelerated cancer-gene discovery.
AB  - PURPOSE OF REVIEW: The completion of the human genome project has enabled several
      new technologies for studying cancer genetics and cancer genomes. However,
      genomic instability and heterogeneity of human tumors impedes a straightforward
      cataloging of cancer genes and possible therapeutic targets. Strategies enabling
      the distinction of causal genetic alterations from bystander genomic noise are
      needed and should significantly speed up the process of cancer-gene discovery.
      RECENT FINDINGS: A series of recent papers described the development of
      integrative oncogenomic approaches based on innovative cancer mouse models and
      how these can be used to speed up the discovery of new cancer genes. In the
      presented studies, spontaneously acquired genetic alterations in mouse tumors of
      defined genetic origin are used to filter/prioritize relevant lesions from
      complex human cancer genomes. As will be discussed in this review, a great
      advantage of this approach is that pinpointed candidate genes can be functionally
      validated in the right genetic context in vivo, which significantly increases
      confidence for later therapeutic development efforts. SUMMARY: The discussed
      approaches hold great promise to speed up the process of cancer-gene discovery
      and should be considered to complement time-consuming and costly endeavors like
      the Cancer Genome Project.

PMID- 18043260
TI  - Class IA phosphoinositide 3-kinase isoforms and human tumorigenesis: implications
      for cancer drug discovery and development.
AB  - PURPOSE OF REVIEW: The phosphoinositide 3-kinases are lipid kinases that are
      activated in response to external factors. They regulate a number of
      intracellular signaling pathways involved in cell motility, metabolism, survival,
      and growth. This review summarizes the current knowledge about specific
      contributions of Class IA phosphoinositide 3-kinases to tumorigenesis and
      presents a rationale for the development of isoform-specific inhibitors. RECENT
      FINDINGS: In the last decade, the Class IA phosphoinositide 3-kinases have gained
      considerable attention as drug targets for the treatment of cancer. Indeed, pan
      phosphoinositide 3-kinase inhibitors are being evaluated in early phases of
      clinical trials for the treatment of multiple human malignancies. Accumulating
      evidence suggests that selectively targeting individual isoforms is also
      possible. However, the patient population that is most likely to benefit from
      such selective compounds remains to be elucidated. SUMMARY: Given the importance
      of the phosphoinositide 3-kinase pathway in the initiation and maintenance of
      human tumors, drugs that effectively target its constituents will be an
      invaluable addition to the arsenal of anticancer therapeutics. However, to fully
      capitalize on the central role of this pathway in malignancy, we must first fully
      understand the nuances of its multiple players.

PMID- 18043261
TI  - Beyond the hypoxia-inducible factor-centric tumour suppressor model of von Hippel
      Lindau.
AB  - PURPOSE OF REVIEW: To provide an overview of the recent advances in the
      understanding of the molecular mechanisms governing the tumour suppressor
      functions of the von Hippel-Lindau protein. RECENT FINDINGS: von Hippel-Lindau is
      a vital component of an E3 ubiquitin ligase complex involved in the oxygen
      dependent targeting of hypoxia-inducible factor for ubiquitin-mediated
      destruction. Recent reports have linked von Hippel-Lindau to the regulation of
      diverse biological processes including cell adhesion, extracellular matrix
      assembly and ciliogenesis in a manner dependent and/or independent of hypoxia
      inducible factor. SUMMARY: The tumour suppressor function of von Hippel-Lindau
      has remained hypoxia-inducible factor-centric since the discovery of von Hippel
      Lindau as a bona fide negative regulator of the ubiquitous oxygen-sensing
      pathway. Emerging evidence supports this hypothesis with the elucidation of
      fundamental cellular processes deregulated upon the inactivation of the von
      Hippel-Lindau-hypoxia-inducible factor pathway, but has also proved compelling on
      the hypoxia-inducible factor-independent tumour suppressor role of von Hippel
      Lindau. These and continuing studies into the molecular pathways and mechanisms
      governing the tumour suppressor functions of von Hippel-Lindau will ultimately
      afford new avenues for anticancer strategies for the improved treatment of a
      diverse array of cancers.

PMID- 18043262
TI  - Restoration of p53 to limit tumor growth.
AB  - PURPOSE OF REVIEW: p53 mutation occurs in over half of all human tumors. Among
      the remaining tumors, although they may process a wild-type p53, the pathways of
      p53-induced cell-cycle arrest and apoptosis are deficient. Therefore, p53 serves
      as a unique molecular target for cancer therapy. This review focuses on the
      current progress regarding restoration of p53 function in human tumors for
      molecularly targeted therapy. RECENT FINDINGS: Targeting p53 for cancer therapy
      has been intensively pursued. CP-31398 was the first small molecule identified
      with the ability to restore the wild-type conformation to mutant p53.
      Subsequently, PRIMA-1 and ellipticine were found to be able to induce mutant p53
      dependent cell death. Nutlin was developed to rescue wild-type p53 from
      degradation mediated by MDM2. More recently, p53 family members can be activated
      and therefore serve as substitutes of p53 in tumor cells and induce cell death.
      SUMMARY: Loss of p53 function is a characteristic of almost all human tumors.
      Recent advances demonstrate that reconstitution of p53 function is possible and
      practical as a promising antitumor strategy.

PMID- 18043263
TI  - Therapeutic targeting of apoptosis pathways in cancer.
AB  - PURPOSE OF REVIEW: Anti-apoptotic mechanisms contribute to the development of
      cancer and the resistance of cancer cells to antitumor therapies. This review
      focuses on the progress towards clinical application of therapies that directly
      modulate the apoptosis pathways. RECENT FINDINGS: A growing understanding of the
      mechanisms that control apoptosis has generated a number of strategies for
      modulating apoptotic pathways, including activation of death receptors and
      neutralization of anti-apoptotic proteins. Striking antitumor efficacy has been
      achieved in preclinical cancer models. To date, early-phase testing has not yet
      established the clinical utility of these strategies. SUMMARY: There is every
      reason to be optimistic that the wealth of knowledge about the molecular controls
      of apoptosis will eventually be translated into new clinical therapies for
      cancer. It is likely that the optimum utility of these pro-apoptotic therapies
      will be in combination with other treatment modalities, and careful patient
      selection will be necessary.

PMID- 18043264
TI  - Will targeted therapy hold its promise? An evidence-based review.
AB  - (1) Many of the significant advances in cancer management in recent years have
      centered on the development and introduction of molecularly targeted therapies,
      such as monoclonal antibodies and tyrosine kinase inhibitors.(2) Despite targeted
      therapy that has clearly benefited and even cured certain patients (eg, imatinib,
      trastuzumab), the ultimate goal of curing cancer, and the more immediate goal of
      replacing non-targeted chemotherapies with less toxic, targeted agents has yet to
      be achieved for most cancer patients.(3) Based on a systematic review of
      randomized controlled trials, examples of significant benefits in selected
      cancers are provided:(a) Non-Hodgkin's lymphoma (NHL) - A large meta-analysis and
      several individual randomised, controlled trials (RCTs) report that rituximab
      plus chemotherapy has a major survival advantage over chemotherapy alone in
      patients with NHL; an overview of six clinical trials supports the survival
      benefit of rituximab plus chemotherapy.(b) Renal cell carcinoma (RCC) -
      Temsirolimus or sunitinib has a significant survival benefit relative to
      interferon-alpha, and sorafenib carries such a benefit in patients resistant to
      standard therapy.(c) Colorectal cancer (CRC) - An overview of three RCTs in
      metastatic CRC revealed that bevacizumab plus 5-fluorouracil/leucovorin possesses
      a significant survival advantage over 5-fluorouracil/leucovorin and irinotecan/5
      fluorouracil/leucovorin.(d) Non-small-cell lung cancer (NSCLC) - In refractory
      NSCLC, erlotinib significantly prolongs survival, particularly in nonsmokers, and
      gefitinib may have some utility in patients of Asian ethnicity.(e) Head and neck
      squamous-cell carcinoma (HNSCC) - Cetuximab plus radiotherapy (versus
      radiotherapy alone) significantly improves locoregional control and survival
      (hazard ratio [HR] 0.68; p = 0.005) without worsening radiotherapy-related
      toxicity.

PMID- 18043266
TI  - Bibliography. Current world literature. Endocrine tumors and cancer biology.

PMID- 18043265
TI  - State-of-the-art in the treatment of chronic myeloid leukaemia.
AB  - PURPOSE OF REVIEW: To revise the current goals of therapy of chronic myeloid
      leukaemia and to incorporate the influence of the underlying chronic myeloid
      leukaemia biology on directing therapeutic management. RECENT FINDINGS: The
      management of chronic myeloid leukaemia has been revolutionized by targeted
      molecular therapy that inhibits the ABL kinase activity of the BCR-ABL gene. The
      achievement of a major molecular response with the first tyrosine kinase
      inhibitor to be introduced into clinical practice, imatinib, is a focus of
      therapeutic regimens. Second-generation tyrosine kinase inhibitors are available
      that have more potent effects than imatinib, and have activity against imatinib
      resistant subclones. Strategies to overcome the restoration of BCR-ABL signalling
      and subsequent resistance to therapy include imatinib dose escalation, a more
      potent tyrosine kinase inhibitor, as well as non-BCR-ABL-dependent approaches and
      agents in clinical development. SUMMARY: Therapeutic advances in chronic myeloid
      leukaemia continue to circumvent the challenges of drug resistance and the
      minimal residual leukaemic burden providing effective strategies for future
      therapy.

PMID- 18043268
TI  - Back to the future. Asthma.

PMID- 18043269
TI  - Recent evidence for adverse effects of residential proximity to traffic sources
      on asthma.
AB  - PURPOSE OF REVIEW: A growing body of evidence indicates that residential
      proximity to traffic sources increases the risk for asthma and asthma
      exacerbations. In this review we have considered publications from 2006-2007 that
      examined the impact of residential traffic-related exposures on asthma occurrence
      and severity. RECENT FINDINGS: In these studies, exposures were estimated using
      traffic metrics based on residential distances from major roads and freeways,
      traffic densities around homes, and models of traffic exposure. Overall,
      residential proximity to traffic sources was associated with increased asthma
      occurrence and exacerbations in both children and adults. Land-use regression
      models were superior to individual traffic metrics in explaining the variability
      of traffic-related pollutants. Susceptibility may also play a role in variation
      in the effects of traffic on asthma. SUMMARY: There is consistent evidence that
      living near traffic sources is associated with asthma occurrence and
      exacerbations. Future studies have the opportunity to improve exposure estimates
      by measuring traffic-related pollutants near homes and schools and including
      time/activity patterns in prediction models. Further research is also warranted
      to investigate the differential impact of traffic by genetic and other
      susceptibility factors and to identify specific pollutants that underlie the
      adverse effect of traffic on asthma.

PMID- 18043270
TI  - Asthma and food allergy.
AB  - PURPOSE OF REVIEW: Food allergy associated clinical and social burdens have
      increased substantially in prevalence in the past decade. Coexisting asthma is a
      significant problem as food reactions tend to be more severe when they involve
      the lung. Food allergy also increases asthma morbidity in adults and children.
      RECENT FINDINGS: Especially in early infancy, food allergy can be related to the
      development of future asthma. For diagnosis, cut-off values are very important
      for both specific IgE levels and skin-prick test when interpreting food allergy.
      For the treatment, oral immunotherapy is showing promise for refractory patients
      with IgE-mediated food allergies. SUMMARY: Food allergies can be classified as
      IgE-mediated or non-IgE-mediated. Besides foods, some additives and preservatives
      can also trigger asthma in certain people. Asthma may develop in about 5% of
      individuals who suffer from food allergy and current asthma may be triggered by
      foods among 6-8% of children and 2% of adults. Because of the difficulty of
      confirming diagnosis of food allergy, novel approaches are currently being
      investigated and new therapy modalities are being sought. For total asthma
      control and for better quality of life, steps should be taken to avoid foods in
      cases of food allergy.

PMID- 18043271
TI  - Near-fatal asthma: recognition and management.
AB  - PURPOSE OF REVIEW: Near-fatal asthma continues to be a significant problem
      despite the decline in overall asthma mortality. The purpose of this review is to
      discuss recent advances in our understanding of the pathophysiology, diagnosis
      and treatment of near-fatal asthma. RECENT FINDINGS: Two distinctive phenotypes
      of near-fatal asthma have been identified: one with eosinophilic inflammation
      associated with a gradual onset and a slow response to therapy and a second
      phenotype with neutrophilic inflammation that has a rapid onset and rapid
      response to therapy. Patients who develop sudden-onset near-fatal asthma seem to
      have massive allergen exposure and emotional distress. In stable condition, near
      fatal asthma frequently cannot be distinguished from mild asthma. Diminished
      perception of dyspnea plays a relevant role in treatment delay, near-fatal
      events, and death in patients with severe asthma. Reduced compliance with anti
      inflammatory therapy and ingestion of medications or drugs (heroin, cocaine) have
      been associated with fatal or near-fatal asthma. SUMMARY: Near-fatal asthma is a
      subtype of asthma with unique risk factors and variable presentation that
      requires early recognition and aggressive intervention.

PMID- 18043272
TI  - Physiologic similarities and differences between asthma and chronic obstructive
      pulmonary disease.
AB  - PURPOSE OF REVIEW: This review examines the physiologic mechanisms responsible
      for persistent maximum expiratory airflow limitation in nonsmoking patients with
      acute and chronic moderate to severe persistent asthma in comparison to chronic
      obstructive pulmonary disease. RECENT FINDINGS: The phenomenon of acute but
      reversible loss of lung elastic recoil during acute asthma is reviewed, although
      no plausible pathophysiologic explanation has been offered. Nonsmoking adults
      with stable asthma and persistent maximum expiratory airflow limitation, despite
      optimal polytherapy, were shown to have unsuspected and unexplained marked loss
      of lung elastic recoil in the absence of lung computed tomography scored
      emphysema. This condition resulted in up to 50% reduction in maximum expiratory
      airflow. Furthermore, these patients remain at high risk for adverse clinical
      events, including near-fatal asthma. In chronic obstructive pulmonary disease,
      reduction in maximum expiratory airflow is related to variable extent of loss of
      lung elastic recoil secondary to emphysema and concurrent intrinsic airway
      obstruction or obliteration of small airways. There is also an unexplained loss
      of lung elastic recoil in primary intrinsic small airways disease in the absence
      of emphysema. SUMMARY: Nonsmoking patients with moderate-severe persistent asthma
      and patients with smoking-related chronic obstructive pulmonary disease share
      similar physiologic mechanisms of expiratory airflow limitation, but probably
      caused by different anatomic abnormalities.

PMID- 18043273
TI  - Pathologic similarities and differences between asthma and chronic obstructive
      pulmonary disease.
AB  - PURPOSE OF REVIEW: Classically, asthma and chronic obstructive pulmonary disease
      present distinct clinical, physiologic and pathologic features. However, not
      infrequently, patients may present with overlapping clinical symptoms and
      physiological abnormalities: patients with severe asthma may present with fixed
      airway obstruction and patients with chronic obstructive pulmonary disease may
      have hyperresponsiveness and eosinophilia. At pathological level, inflammatory
      and structural similarities also occur and may be related to the phenotypic
      overlaps. RECENT FINDINGS: In patients with asthma overlaps at inflammatory level
      exist with chronic obstructive pulmonary disease, such as increased neutrophilia
      in patients with severe asthma or an association of CD8+ T cells and lung
      function decline. In chronic obstructive pulmonary disease, minimizing
      eosinophilia may be important to reduce exacerbations. Structural alterations
      occur in both diseases, but involving airway compartments differently. Airway
      epithelial changes, extracellular matrix deposition and mucus gland hypertrophy
      occur in both diseases. Asthmatics have thicker reticular basement membrane and
      more prominent smooth-muscle abnormalities, whereas emphysema is a distinct
      feature of chronic obstructive pulmonary disease. SUMMARY: Recognizing the
      differences and similarities at pathological level in both diseases may lead to a
      better understanding of the overlapping clinical and physiological phenotypes,
      thereby helping to better plan specific treatment and long-term management.

PMID- 18043274
TI  - Provocative challenges to help diagnose and monitor asthma: exercise,
      methacholine, adenosine, and mannitol.
AB  - PURPOSE OF REVIEW: To review bronchial provocations tests used in the measurement
      of bronchial hyperresponsiveness to help in the diagnosis of asthma. RECENT
      FINDINGS: The bronchial provocations tests reviewed include exercise,
      methacholine, AMP and mannitol, with reference to methodology and monitoring of
      treatment. SUMMARY: Methacholine is used for identifying bronchial
      hyperresponsiveness and to guide treatment. Exercise is used as a bronchial
      provocation test because demonstrating prevention of exercise-induced asthma is
      an indication for use of a drug. Both of these tests are being used to study
      tolerance to beta2 agonists. There is increasing use of eucapnic voluntary
      hyperpnea as a surrogate bronchial provocation test for exercise to identify
      exercise-induced asthma, particularly in athletes. For methacholine and AMP there
      is concern about the different breathing patterns used to inhale these aerosols
      and the impact they have on the cutoff point for identifying bronchial
      hyperresponsiveness. A new test that uses a kit containing prepacked capsules of
      different doses of mannitol and a delivery device is discussed. There is
      increasing interest in using tests that act indirectly by release of mediators
      because the bronchial hyperresponsiveness itself is an indicator of the presence
      of inflammation. Since treatment of inflammation leads to loss of bronchial
      hyperresponsiveness to indirect stimuli, these tests are well suited to identify
      success of treatment.

PMID- 18043275
TI  - Guidelines management of asthma in a busy urban practice.
AB  - PURPOSE OF REVIEW: The purpose of this article is to review how optimal asthma
      management can be applied in a variety of clinical settings that are used to care
      for high-risk, urban asthma patients, especially those who live in the inner
      city, utilizing the 2007 National Heart, Lung, and Blood Institute/National
      Asthma Education Prevention Program 'Guidelines for the diagnosis and management
      of asthma', and adapting them to be applied in a variety of urban clinical
      settings, independent of practice infrastructure. RECENT FINDINGS: Previous
      asthma guidelines stressed asthma severity classification. A renewed focus on
      asthma control has led to better asthma outcomes. Consequently, it was deemed
      necessary to establish a new asthma paradigm that characterizes both asthma
      severity and control within the context of current impairment and future risk.
      This new paradigm can be effectively applied to high-risk, inner-city asthma
      patients, while allowing for individualization of care within systems of varied
      healthcare delivery infrastructures. SUMMARY: Assessment of asthma severity and
      control, with special emphasis on literacy and ethno-cultural beliefs and
      philosophies, will facilitate appropriate adaptations of long-term asthma
      management to provide optimal outcomes in urban asthmatics. It is essential to
      anticipate the worst-case, while planning for the best-case scenario.

PMID- 18043276
TI  - Role of long-acting beta2-adrenergic agonists in asthma management based on
      updated asthma guidelines.
AB  - PURPOSE OF REVIEW: This review examines the role of long-acting beta2-adrenergic
      agonists in the management of asthma, particularly focusing on recommendations in
      the newly revised Global Initiative for Asthma (GINA) and National Heart, Lung,
      and Blood Institute (NHLBI) asthma guidelines. RECENT FINDINGS: GINA guidelines
      recommend increasing inhaled corticosteroid doses in all children with asthma not
      controlled on low-dose inhaled corticosteroids before adding a long-acting beta2
      adrenergic agonist, whereas NHLBI guidelines have different age-based
      recommendations for children. In patients younger than 5 years, NHLBI guidelines
      recommend increasing the inhaled corticosteroid dose before adding a long-acting
      beta2-adrenergic agonist; in children aged 5-11 years, equal weight is given to
      increasing the inhaled corticosteroid dose or including add-on therapy to low
      dose inhaled corticosteroids. In adults and adolescents aged 12 years and older,
      GINA recommends adding long-acting beta2-adrenergic agonists to low-dose inhaled
      corticosteroids over increasing the inhaled corticosteroid dose. NHLBI guidelines
      give equal weight to these choices, with alternative, although not preferred,
      therapies including the addition of theophylline, zileuton, or leukotriene
      receptor antagonists to low-dose inhaled corticosteroids. SUMMARY: In the
      recently updated GINA and NHLBI asthma guidelines, long-acting beta2-adrenergic
      agonists are an important class of agents for the management of persistent asthma
      in patients whose asthma is not well controlled with inhaled corticosteroid
      monotherapy.

PMID- 18043277
TI  - Safety of long-acting beta-agonists in asthma: a review.
AB  - PURPOSE OF REVIEW: This review highlights a growing literature regarding the
      safety of long-acting beta-2 agonists as add-on therapy to inhaled
      corticosteroids. RECENT FINDINGS: Two studies have demonstrated a mortality
      increase with use of long-acting beta-2 agonists in asthmatic patients. They were
      not well controlled and thus raise the question of whether this mortality
      increase was the result of using long-acting beta-2 agonists as monotherapy or
      whether there is some rare susceptibility to an untoward effect of this class of
      medicine. SUMMARY: When inhaled corticosteroids and long-acting beta-2 agonists
      are used in combination, prospective studies demonstrate improvement in asthma
      control and exacerbation rate. Two studies showed an increase in asthma mortality
      with long-acting beta-2 agonists, but they allowed beta-2 agonists to be used as
      monotherapy and did not address the safety of their appropriate use in
      conjunction with inhaled corticosteroids. Although the majority of asthmatic
      patients appear to benefit from the use of long-acting beta-2 agonists, a small
      subclass may be prone to deleterious effect. It is uncertained whether this is
      some rare susceptibility to these drugs, or, more likely, that this is the
      consequence of monotherapy with long-acting beta-2 agonists controlling the signs
      and symptoms while masking inflammation.

PMID- 18043278
TI  - The role of magnesium sulfate in the acute and chronic management of asthma.
AB  - PURPOSE OF REVIEW: Acute asthma is common and severe exacerbations may result in
      hospitalization, need for endotracheal intubation and, rarely, death. Standard
      emergency care includes systemic corticosteroids and bronchodilators, but
      additional treatments may be required in severe cases. We summarize the
      substantial evidence regarding the role of MgSO4 in acute asthma and comments on
      the potential benefit in chronic asthma. RECENT FINDINGS: Inhaled and intravenous
      MgSO4 agents are used in the treatment of acute asthma, but only the intravenous
      formulation is effective. In severe asthma exacerbations, a single bolus dose of
      intravenous MgSO4 reduces admissions and improves pulmonary functions. Inhaled
      MgSO4 is more effective than placebo as a bronchodilator, but performs no better
      than salbutamol and there is no apparent synergy when the two are combined.
      Whereas intravenous MgSO4 treatments appear to be effective, long-term
      'replacement' therapy with magnesium does not appear to affect chronic asthma.
      SUMMARY: Evidence suggests that intravenous MgSO4 is beneficial in acute asthma,
      while the evidence for inhaled MgSO4 is less convincing. Moreover, the role of
      replacement therapy with oral magnesium remains to be clarified. The use of
      intravenous MgSO4 remains uncommon, with emergency physicians appropriately
      restricting its use to patients with severe exacerbations.

PMID- 18043279
TI  - New interventions in asthma including bronchial thermoplasty.
AB  - PURPOSE OF REVIEW: This article focuses on two novel asthma therapies -
      antibiotics and a procedure, bronchial thermoplasty. The challenges of
      identifying which treatment would best help an individual patient can be
      addressed by use of noninvasive measurements to define their asthma. RECENT
      FINDINGS: Asthma is heterogeneous. Methods can be applied that define different
      phenotypes. We can now obtain a more detailed description of physiological
      changes, for example with bronchial provocation, and inflammatory changes, for
      example with exhaled nitric oxide or sputum cell analysis, in patients with
      airway symptoms. These measurements help define disease mechanisms and are
      especially informative when patients do not respond to standard therapy.
      Furthermore, detailed phenotyping may help identify who is most likely to benefit
      from newly developed, more specific therapies ranging from antagonists of
      individual mediators, for example anti-tumor necrosis factor-alpha or anti
      immunoglobulin E, to interventions that directly address structural determinants
      of asthma, for example bronchial thermoplasty. SUMMARY: Asthma treatment is
      evolving beyond the current cornerstones of bronchodilation, leukotriene
      antagonism and corticosteroids. This change will be propelled by a more detailed
      description of individual patients' disease that will enable customization of
      treatment, and the development of specific interventions that modify disease
      mechanisms, including airway remodelling.

PMID- 18043280
TI  - Bibliography. Current world literature. Asthma.

PMID- 18043281
TI  - Global expression analysis of prostate cancer-associated stroma and epithelia.
AB  - Characterization of gene expression profiles in tumor cells and the tumor
      microenvironment is an important step in understanding neoplastic progression. To
      date, there are limited data available on expression changes that occur in the
      tumor-associated stroma as either a cause or consequence of cancer. In the
      present study, we employed a 54,000 target oligonucleotide microarray to compare
      expression profiles in the 4 major components of the microenvironment: tumor
      epithelium, tumor-associated stroma, normal epithelium, and normal stroma. Cells
      from 5 human, whole-mount prostatectomy specimens were microdissected and the
      extracted and amplified mRNA was hybridized to an Affymetrix Human Genome U133
      Plus 2.0 GeneChip. Using the intersection of 2 analysis methods, we identified
      sets of differentially expressed genes among the 4 components. Forty-four genes
      were found to be consistently differentially expressed in the tumor-associated
      stroma; 35 were found in the tumor epithelium. Interestingly, the tumor
      associated stroma showed a predominant up-regulation of transcripts compared with
      normal stroma, in sharp contrast to the overall down-regulation seen in the tumor
      epithelium relative to normal epithelium. These data provide insight into the
      molecular changes occurring in tumor-associated stromal cells and suggest new
      potential targets for future diagnostic, imaging, or therapeutic intervention.

PMID- 18043282
TI  - Evaluation of whole genome amplification protocols for array and oligonucleotide
      CGH.
AB  - Genome-based technologies such as genomic arrays and next generation sequencing
      are poised to make significant contributions to clinical oncology. However,
      translation of these technologies to the clinic will require that they produce
      high-quality reproducible data from small archived tumor specimens and biopsies.
      Herein, we report on a systematic and comprehensive microarray analysis comparing
      multiple whole genome amplification methods using a variety of difficult clinical
      specimens, including formalin-fixed and paraffin-embedded tissues. Quantitative
      analysis and clustering suggest that Sigma's whole genome amplification protocol
      performed best on all specimens and, moreover, worked well with a formalin-fixed,
      paraffin-embedded biopsy.

PMID- 18043283
TI  - Fluorescence in situ hybridization (FISH) as primary methodology for the
      assessment of HER2 Status in adenocarcinoma of the breast: a single institution
      experience.
AB  - The demand for both reflexed and primary fluorescence in-situ hybridization
      (FISH) testing in the clinical setting is increasing. Relevant literature has
      reported the incidence of HER2 overexpression in 20% to 30% of cases, but some
      reports suggest that HER2 gene amplification rates are substantially lower.
      Published data, however, on primary FISH assessment from a single institution is
      limited, especially information about the frequency of the anomalous genotypes
      defined by FISH. We report our experience with primary FISH testing in 742
      consecutive cases of breast cancer, in the calendar year 2006. Eighty percent
      (595/742) of the breast cancer cases were not amplified for HER2 (HER2/CEP17=0.8
      1.9), whereas 19% (142/742) of cases were HER2 amplified (HER2/CEP17>or=2.0).
      Among the HER2-amplified cases, 3% (19/742) were low-level amplified (HER2/CEP17
      ratio=2.0-2.5). Genotypic heterogeneity, defined as >5% but <50% of the tumor
      cells demonstrating HER2 gene amplification, was observed in 5% (40/7242) of the
      cases. HER2 monoallelic deletion (HER2/CEP17<or=0.7) was demonstrated in 2%
      (12/742) of the cases and CEP17 monosomy (1 CEP17 signal in >80% of tumor cells)
      was observed in 2% (13/742). Polysomy, if defined as CEP17 spot count 3.0 or more
      in at least 80% of tumor cells, was observed in 3% (20/742) of the cases. These
      data may be helpful as benchmarks for other institutions initiating primary FISH
      analysis for HER2 genotyping.

PMID- 18043284
TI  - Molecular and immunohistochemical analysis of ERBB2 expression in correlation
      with proliferation rate in synovial sarcoma.
AB  - The aim of the study was to determine whether or not the tyrosine kinase receptor
      ERBB2 is overexpressed in synovial sarcomas (SSs). We also focused on the cell
      cycle-related nuclear protein-Ki-67. Thirty-two samples were available for
      immunohistochemistry and only 1 case revealed a weak diffuse membrane ERBB-2
      staining. The remaining cases showed either no staining (20 cases) or weak focal
      membrane staining (9 cases). In our 3 highly overexpressed ERBB2 mRNA samples,
      fluorescence in situ hybridization showed no amplification of the ERBB2 gene.
      ERBB2 mRNA expression was present in all samples of SSs at a comparable level to
      that in breast carcinoma control group, with a 2+ or 3+ immunopositivity. The
      high level of ERBB2 mRNA expression correlated with a high level of Ki-67 mRNA.
      The level of Ki-67 mRNA correlated with Ki-67 protein expression. The study shows
      that ERBB2 mRNA expression is very strong in SSs, but the membrane ERBB-2 protein
      expression is practically absent.

PMID- 18043285
TI  - Molecular differentiation of early and late stage laryngeal squamous cell
      carcinoma: an exploratory analysis.
AB  - BACKGROUND: A current shortcoming in cancer prognostication and treatment is a
      lack of methods that adequately address the complexity and diversity of the
      disease. Prognostic marker systems based on single parameters have generally
      proven inadequate. Thus, multiparametric methods, which rely on many pieces of
      information, are ideally suited to the grouping of tumor subtypes and the
      identification of specific patterns of disease progression. DESIGN: This study
      investigated, on an exploratory basis, whether genome wide alterations of loss
      and gain, using a panel of 122 gene probes (112 unique genes), discriminated
      between early stage (stage 1 and 2) and late stage (stage 3 and 4) laryngeal
      squamous cell carcinomas (LSCC). The LSCC cohort comprised 29 patients, 12 early
      and 17 late staged. Formalin-fixed LSCC DNA was interrogated by a genome wide
      candidate gene panel (122 genes) using the multiplex ligation-dependent probe
      amplification assay. RESULTS: Statistical analysis employed the nonparametric
      Wilcoxon 2-sample test. Significant differences between tumor stages of early
      versus late were seen for the following genes: ERBB4, CASP2, RECQL4, and BCL7A.
      Loss of ERBB4 (P=0.045) and BCL7A (P=0.019) significantly discriminated between
      early and late stage LSCC. Gain of RECQL4 copy number (P=0.043) was associated
      with late LSCC. Gain of CASP2 (P=0.043) marked early LSCC, whereas loss was
      associated with late LSCC. CONCLUSIONS: High-throughput genome wide approaches
      have the potential to yield discrete gene repertoires of early and late stage
      LSCC differentiation.

PMID- 18043286
TI  - The E-cadherin repressor snail plays a role in tumor progression of endometrioid
      adenocarcinomas.
AB  - Endometrial cancer is the most common gynecologic cancer in the developed world.
      The cell-adhesion protein E-cadherin acts as a tumor-suppressor protein and is
      down-regulated by the transcription factor Snail, whose expression was shown to
      be associated with estrogen receptor signaling. This study aimed to investigate
      the expression of E-cadherin, Snail, and estrogen-receptor alpha in 87 primary
      tumors and 26 metastases of endometroid endometrial carcinomas. Reduced E
      cadherin immunoreactivity was seen in 44.8% of the primary tumors and 65.4% of
      the metastases with a statistical correlation to higher tumor grade (P=0.003)
      only in metastatic lesions. About 28.7% of primary tumor specimens showed a
      positive Snail immunoreactivity that was correlated with reduced estrogen
      receptor alpha expression (P=0.047). Positive Snail immunoreactivity was also
      seen in 53.8% of the metastases where it was correlated with higher tumor grade
      (P=0.003) and abnormal E-cadherin expression (P=0.003). Interestingly, a Snail
      expressing endometrial carcinoma-cell line showed a higher migration potential
      than a variant of this cell line with low levels of Snail. Taken together, our
      data are in line with a proposed role for Snail in endometrial tumor progression.

PMID- 18043287
TI  - Hedgehog pathway expression in heterogeneous pancreatic adenocarcinoma:
      implications for the molecular analysis of clinically available biopsies.
AB  - Recent studies suggest that hedgehog (HH)-pathway signaling is required for the
      initiation and continued growth of pancreatic adenocarcinoma (PAC). Definitive
      gene expression analysis of PAC remains difficult, owing to the host desmoplastic
      stromal interaction and subsequent tumor heterogeneity. The primary goal of this
      study was to evaluate the effect of heterogeneity within a series (n=5) of
      matched clinical PAC biopsies [snap-frozen, formalin-fixed paraffin-embedded
      (FPE), endoscopic ultrasound-guided fine-needle aspirate (EUS-FNA)]. Differential
      expressions, specific to tumor cells, were evaluated by comparisons of uninvolved
      pancreas (n=9), EUS-FNA (n=14), and macrodissected (tumor-cell-enriched) biopsies
      (n=16). To determine whether treatment modulates gene expression, a unique
      (independent) set of synchronous EUS-FNA samples (n=4) was obtained before, and 2
      weeks after, chemoradiation. mRNA levels were evaluated using real-time
      quantitative polymerase chain reaction formatted in a TaqMan low-density array,
      which was capable of simultaneously quantifying 46 independent genes in the HH
      pathway. Protein levels for Patched, Smoothened, and glioma-associated oncogene 1
      (Gli-1) in FPE tissues were determined, using immunohistochemistry. A significant
      concordance (P<0.0001) was observed in the HH-pathway mRNA levels between matched
      surgically resected (both snap-frozen and FPE) and EUS-FNA biopsies. HH-pathway
      mRNA levels changed (increased) only after macrodissection, suggesting
      localization to tumor cells. Immunohistochemical staining for Patched,
      Smoothened, and Gli-1 confirmed the increased (P<0.001) levels of protein in the
      PAC cells, compared with cells from uninvolved pancreas. EUS-FNA biopsies that
      were obtained before and during chemoradiation demonstrated no significant
      changes in HH-pathway gene expression. Collectively, these studies demonstrate
      presence of HH-pathway expression in all the clinical PAC biopsies examined,
      suggesting that this is a significant tumor-associated target and offering the
      possibility that specific molecular profiling might be attempted from these
      heterogeneous tissues.

PMID- 18043288
TI  - A novel mitochondrial DNA tRNAIle (m.4322dupC) mutation associated with
      idiopathic dilated cardiomyopathy.
AB  - We identified a novel heteroplasmic mitochondrial DNA (mtDNA) (m.4322dupC)
      mutation in tRNA gene associated with isolated dilated cardiomyopathy (DCM) as
      maternal trait. Mutation screening techniques and automated DNA sequencing were
      performed to identify mtDNA mutations and to assess heteroplasmy in family's
      proband and healthy control subjects. All family members tested had heteroplasmic
      mtDNA m.4322dupC mutation. We also screened 350 normal controls for this mutation
      and found no evidence of heteroplasmy. The m.4322dupC mutation was found in the
      skeletal tissue from the proband that exhibited slightly reduced deficiency of
      mitochondrial respiratory chain enzymes (complex III). The present study reports
      the novel m.4322dupC mutation in tRNA gene, which is possibly associated to the
      disease, to isolated DCM. It was localized in a hot-spot region for mutations and
      is possibly pathogenic because of a cosegregation with the matrilineal
      transmission of DCM.

PMID- 18043289
TI  - Malignant ectomesenchymoma: genetic profile reflects rhabdomyosarcomatous
      differentiation.
AB  - Malignant ectomesenchymoma (MEM) represents a heterogeneous group of tumors, most
      likely originating from pluripotent primitive neural crest cells. In this report,
      we present an 8-month-old infant boy with an MEM on the left scrotum.
      Retrospective review of the incision biopsy showed the presence of a few ganglion
      cells in an otherwise classic embryonal rhabdomyosarcoma (RMS), whereas in the
      resection specimen after chemotherapy the combined RMS and ganglioneuroma
      components were very obvious. Cytogenetic analysis of the residual lesion showed
      an abnormal karyotype, 49, XY, +2, -6, +11, +20, +mar, with a hyperploidy in a
      subset of cells. By fluorescence in situ hybridization analysis, the marker
      chromosome was identified as originating from chromosome 6, and the tumor cells
      were negative for PAX3/PAX7 disrupting translocations specific for alveolar RMS.
      Gains of chromosomes 2, 11, and 20, found in the current case, are a common
      finding in embryonal RMS. These gains probably reflect the myogenic
      differentiation of MEM and support the genetic link between these 2 neoplasms. In
      addition to the conventional cytogenetics, array comparative genomic
      hybridization analysis was performed on the primary and residual tumors. The
      genomic profiles of both specimens were basically the same including the presence
      of 2 distinctive chromosome 6p21.32-p21.2 and 6p11.2 amplification regions in the
      primary tumor, which vanished in the postchemotherapy specimen. The pretreatment
      biopsy exhibited strong expression of HMGA1 and HMGA2 proteins in
      immunohistochemistry, with the shift toward the loss of expression of both genes
      in the posttreatment tumoral tissue. This finding supports the oncogenic
      properties of the HMGA family of proteins and their role in the process of
      malignant transformation.

PMID- 18043290
TI  - Future perspectives in cardiac rehabilitation: a new European Association for
      Cardiovascular Prevention and Rehabilitation Position Paper on 'secondary
      prevention through cardiac rehabilitation'.

PMID- 18043291
TI  - Climate change and preventive medicine.
AB  - Thermal stress, food poisoning, infectious diseases, malnutrition, psychiatric
      illness as well as injury and death from floods, storms and fire are all likely
      to become more common as the earth warms and the climate becomes more variable.
      In contrast, obesity, type II diabetes and coronary artery disease do not result
      from climate change, but they do share causes with climate change. Burning fossil
      fuels, for example, is the major source of greenhouse gases, but it also makes
      pervasive physical inactivity possible. Similarly, modern agriculture's enormous
      production of livestock contributes substantially to greenhouse gas emissions,
      and it is the source of many of our most energy-rich foods. Physicians and
      societies of medical professionals have a particular responsibility, therefore,
      to contribute to the public discourse about climate change and what to do about
      it.

PMID- 18043292
TI  - Physical activity and the elderly.
AB  - Functional ageing processes are characterized by a loss of performance
      capabilities regarding coordination, flexibility, strength, speed, and endurance.
      The effects of ageing processes on the cardiovascular system and skeletal muscle
      are the foci of attention. After age 30, the maximum aerobic dynamic performance
      capacity decreases by an average of 8% per decade. The causes are mainly a
      reduction in the maximum cardiac output and decreases in capillarization and in
      the skeletal muscle mass. An improvement in the maximum oxygen uptake by 18% and
      in the aerobic-anaerobic threshold by 22% was achieved in untrained men aged 55
      70 years, in a 12-week-long bicycle ergometer-training programme. The strength of
      the skeletal muscle decreases particularly after 50-60 years of age. The main
      cause is the reduction in the number of motor units and muscle fibres. Further,
      modifications of the endothelial function and the development of sarcopenia are
      of particular importance in ageing processes. General aerobic dynamic training
      can improve the endothelial function in old age and thus help prevent
      cardiovascular diseases. Strength training is most appropriate for the prevention
      of sarcopenia. Imaging techniques over the last 20 years have provided new
      findings on the influence and the significance of physical activity on the brain.
      We call this new interdisciplinary area 'Exercise Neuroscience'. Demands on
      coordination and aerobic dynamic endurance are suitable in counteracting age
      related neuronal cellular loss, synapsis hypotrophy, and in improving
      neurogenesis and capillarization. Adjusted physical activity is thus capable of
      counteracting age-related changes and performance loss not only in the
      cardiovascular system but also in the brain.

PMID- 18043293
TI  - Anthropometric measures and absolute cardiovascular risk estimates in the
      Australian Diabetes, Obesity and Lifestyle (AusDiab) Study.
AB  - BACKGROUND: Framingham risk functions are widely used for prediction of future
      cardiovascular disease events. They do not, however, include anthropometric
      measures of overweight or obesity, now considered a major cardiovascular disease
      risk factor. We aimed to establish the most appropriate anthropometric index and
      its optimal cutoff point for use as an ancillary measure in clinical practice
      when identifying people with increased absolute cardiovascular risk estimates.
      DESIGN: Analysis of a population-based, cross-sectional survey was carried out.
      METHODS: The 1991 Framingham prediction equations were used to compute 5 and 10
      year risks of cardiovascular or coronary heart disease in 7191 participants from
      the Australian Diabetes, Obesity and Lifestyle Study (1999-2000). Receiver
      operating characteristic curve analysis was used to compare measures of body mass
      index (BMI), waist circumference, and waist-to-hip ratio in identifying
      participants estimated to be at 'high', or at 'intermediate or high' absolute
      risk. RESULTS: After adjustment for BMI and age, waist-to-hip ratio showed
      stronger correlation with absolute risk estimates than waist circumference. The
      areas under the receiver operating characteristic curve for waist-to-hip ratio
      (0.67-0.70 in men, 0.64-0.74 in women) were greater than those for waist
      circumference (0.60-0.65, 0.59-0.71) or BMI (0.52-0.59, 0.53-0.66). The optimal
      cutoff points of BMI, waist circumference and waist-to-hip ratio to predict
      people at 'high', or at 'intermediate or high' absolute risk estimates were 26
      kg/m2, 95 cm and 0.90 in men, and 25-26 kg/m2, 80-85 cm and 0.80 in women,
      respectively. CONCLUSIONS: Measurement of waist-to-hip ratio is more useful than
      BMI or waist circumference in the identification of individuals estimated to be
      at increased risk for future primary cardiovascular events.

PMID- 18043294
TI  - Effects of chronic exercise on endothelial dysfunction and insulin signaling of
      cutaneous microvascular in streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Abnormalities of the modulatory roles played by the endothelium
      and/or smooth muscle may be critical and initiating factors in the development of
      diabetic vascular disease. Decreased phosphatidylinositol 3-kinase (PI3-K)/Akt
      pathway activity and impaired nitric oxide production through this pathway may
      play pivotal roles in the diabetes-induced vascular dysfunction. Several findings
      have demonstrated that exercise training has therapeutic and protective effects
      in type 1 diabetes and could correct endothelial dysfunction. The molecular
      mechanisms, however, are only partially understood. METHOD: Male Wistar rats
      (220+/-10 g, N=60) were made diabetic by streptozotocin (60 mg/kg,
      subcutaneously). After 1 week of diabetes induction, animals were submitted to
      exercise training for 10 weeks on a treadmill. To characterize cutaneous
      microvascular responses by laser Doppler flowmetery, animals were deeply
      anesthetized by intraperitoneal injection of pentobarbital sodium (60 mg/kg) and
      placed on a heating pad. A rectal thermometer was inserted and body temperature
      was maintained at 37+/-0.5 degrees C. A tracheotomy was performed to minimize
      respiratory difficulties. Systemic arterial blood pressure and heart rate were
      measured by using a tail-cuff during assessment of cutaneous blood flow. RESULTS:
      (i) Acetylcholine-induced cutaneous perfusion were increased significantly by
      training in the diabetic groups; (ii) Cutaneous microvascular responses to sodium
      nitroprusside did not alter in control and diabetic animals by training; and
      (iii) Local microinjection of insulin increased cutaneous blood flow in trained
      diabetic and trained control rats compared with age-matched sedentary diabetic
      and sedentary control normal rats. The administration of wortmannin (PI3K
      inhibitor) and N-nitro-L-arginine ( nitric oxide synthase inhibitor) before
      insulin, however, attenuated the increase in cutaneous blood flow in trained
      diabetic and normal rats. CONCLUSIONS: Chronic exercise improved endothelium
      dependent dilatation and potentiated insulin vascular function, possibly by PI3
      kinase pathway in diabetic rats.

PMID- 18043295
TI  - Running speed and maximal oxygen uptake in rats and mice: practical implications
      for exercise training.
AB  - Valid and reliable experimental models are essential to gain insight into the
      cellular and molecular mechanisms underlying the beneficial effects of exercise
      in prevention, treatment, and rehabilitation of lifestyle-related diseases.
      Studies with large changes, low variation, and reproducible training outcome
      require individualized training intensity, controlled by direct measurements of
      maximal oxygen uptake or heart rate. As this approach is expensive and time
      consuming, we discuss whether maximal treadmill running speed in a gradually
      increasing ramp protocol might be sufficient to control intensity without losing
      accuracy. Combined data from six studies of rats and mice from our lab
      demonstrated a close correlation between running speed and oxygen uptake. This
      relationship changed towards a steeper linear slope after endurance training,
      indicating improved work economy, that is, less oxygen was consumed at fixed
      submaximal running speeds. Maximal oxygen uptake increased 40-70% after high
      intensity aerobic interval training in mice and rats. The speed at which oxygen
      uptake reached a plateau, increased in parallel with the change in maximal oxygen
      uptake during the training period. Although this suggests that running speed can
      be used to assess training intensity throughout a training program, the problem
      is to determine the exact relative intensity related to maximal oxygen uptake
      from running speed alone. We therefore suggest that directly measured oxygen
      uptake should be used to assess exercise intensity and optimize endurance
      training in rats and mice. Running speed may serve as a supplement to ensure this
      intensity.

PMID- 18043296
TI  - Estimation of 10-year risk of fatal cardiovascular disease and coronary heart
      disease in Iceland with results comparable with those of the Systematic Coronary
      Risk Evaluation project.
AB  - BACKGROUND: No data are available on the comparison between an absolute 10-year
      risk of fatal cardiovascular disease (CVD) and coronary heart disease (CHD)
      morbidity using the risk assessments of the Systematic Coronary Risk Evaluation
      (SCORE) project. DESIGN: Data from the prospective Reykjavik Study of 15,782
      patients were used to estimate the 10-year risk of fatal CVD and CHD morbidity in
      Iceland. METHODS: Survival to fatal CVD event was defined as in the SCORE
      project. Survival to CHD morbidity was defined as having a myocardial infarction,
      coronary artery bypass graft, or angioplasty. The statistical methodology of
      SCORE was used. RESULTS: Relative risk in Iceland was comparable with SCORE
      results but baseline risk was similar to the low-risk version of SCORE, which
      contradicted previous suggestions for the countries of northern Europe.
      Correlation between absolute risk of CHD morbidity and risk for fatal CVD was
      high (r=0.96), resulting in similar ranking of individuals by risk and
      discriminatory capacity. This is the first published comparison between total
      fatal CVD risk and CHD morbidity in a population-based cohort using the current
      risk assessment guidelines of the European Societies on Coronary Prevention.
      CONCLUSIONS: Risk for fatal CVD in Iceland has the same characteristics as those
      in a European nation with results varying in accordance with the SCORE project.
      The risk estimate to be used, CHD morbidity or fatal CVD, is a choice of clinical
      preference. The data, however, suggest that 5% high-risk threshold of fatal CVD
      corresponds to a 12% CHD-morbidity risk, which is a significant change from the
      conventional reference value of 20%.

PMID- 18043297
TI  - Alcohol consumption, alcohol dehydrogenase and risk of coronary heart disease in
      the MONICA/KORA-Augsburg cohort 1994/1995-2002.
AB  - BACKGROUND: Ample evidence exists for a protective effect of moderate alcohol
      consumption on cardiovascular risk. Recently, genotype of alcohol dehydrogenase
      1C (ADH1C) has been reported to modify the impact of alcohol consumption on the
      risk of coronary heart disease (CHD). This study investigates whether ADH1C
      genotype modifies the effect of alcohol consumption on CHD risk and high-density
      lipoprotein (HDL) cholesterol level. DESIGN: Prospective cohort study. METHODS:
      Analyses of the joint effects of alcohol consumption and ADH1C genotype on CHD
      risk and HDL cholesterol level using Cox proportional hazards models and linear
      models. RESULTS: Participants who were homozygous or heterozygous for the slow
      metabolizing gamma2-allele and reported alcohol intake of more than 14 g/day
      showed a 64% [hazard rate ratio (HRR), 0.36; 95% confidence interval (CI), 0.16
      0.80] reduction in CHD risk. This effect was particularly pronounced in men (HRR,
      0.27; 95% CI, 0.11-0.67). Women who reported alcohol intake > or =2 g/day showed
      a nonsignificant risk reduction (HRR, 0.39; 95% CI, 0.07-2.17). No significant
      interactions were found among alcohol consumption, ADH1C genotype, and HDL
      cholesterol levels. CONCLUSIONS: In this study, alcohol dehydrogenase modifies
      the effect of alcohol consumption on coronary risk. The results support the
      protective effect of alcohol consumption on CHD risk and suggest a causal
      association of alcohol intake and lower CHD risk. The impact of ADH1C on the
      relationship between alcohol and HDL cholesterol is less clear.

PMID- 18043298
TI  - Prevalence and determinants of prehypertension among African Surinamese,
      Hindustani Surinamese, and White Dutch in Amsterdam, the Netherlands: the SUNSET
      study.
AB  - BACKGROUND: Evidence suggests that prehypertension is associated with increased
      risk of cardiovascular mortality. Little is known about ethnic differences in
      prehypertension in Europe. We aimed to assess these ethnic differences and to
      determine the factors associated with prehypertension in Amsterdam, the
      Netherlands. DESIGN: Cross-sectional study. METHODS: Prehypertension was defined
      as having a blood pressure 120-139/80-89 mmHg. RESULTS: The overall prevalence of
      prehypertension was 32.8% (men 37.9% and women 29.9%). The prevalence of
      prehypertension did not differ between the ethnic groups in men. African
      Surinamese and Hindustani Surinamese women, however, had a higher prevalence of
      prehypertension than White Dutch women. In multivariate logistic regression
      analysis, the odds ratios [95% confidence interval] for being prehypertensive
      were 2.25 (1.38-3.67; P<0.001) for African Surinamese and 2.06 (1.18-3.60;
      P<0.01) for Hindustani Surinamese women, compared with White Dutch women. BMI was
      strongly associated with prehypertension in both men and women. Total cholesterol
      was positively associated with prehypertension in women, whereas increased
      physical activity was negatively associated. The independent factors associated
      with prehypertension vary by ethnic group. In men, BMI was associated with
      prehypertension in the White Dutch, total cholesterol and low education in the
      African Surinamese, and fasting glucose in the Hindustani Surinamese. In women,
      total cholesterol was associated with prehypertension in the African Surinamese;
      the corresponding factor was the BMI in the Hindustani Surinamese. CONCLUSION:
      Prehypertension is common in minority women. As a large proportion of people with
      prehypertension progress to clinical hypertension, targeting these people early
      with lifestyle-modification interventions aimed at weight loss, increased
      physical activity, and healthy dietary habits can provide important long-term
      benefits. The results indicate that the primary foci of such lifestyle
      interventions should vary between ethnic groups.

PMID- 18043299
TI  - Relation of depression to various markers of coagulation and fibrinolysis in
      patients with and without coronary artery disease.
AB  - BACKGROUND: It has been suggested that changes in blood coagulation and
      fibrinolysis might explain the observed association between depression and
      coronary artery disease (CAD). So far, only a few coagulation factors have been
      investigated in this regard, and the results were not consistent. DESIGN: The aim
      of our study was to analyse a broad range of coagulation and fibrinolytic
      factors, with emphasis on factors directly involved in clot formation and
      degradation or reflecting coagulation activation, in patients with CAD and
      controls without CAD, as assessed by coronary angiography, who also underwent a
      diagnostic procedure for depression. METHODS: We screened 306 patients with CAD
      and controls without CAD for depression using the Hospital Anxiety and Depression
      Scale and Allgemeine Depressions Skala-L questionnaires. In participants with
      positive screening result, diagnosis of major depression was confirmed or
      excluded by a structured interview. We analysed the following coagulation and
      fibrinolytic factors: fibrinogen, prothrombin fragment F1+2, factor XIII A
      subunit, factor XIII B-subunit, tissue plasminogen activator, plasminogen
      activator inhibitor-1, thrombin-activable fibrinolysis inhibitor, and D-dimer.
      RESULTS: We did not observe significant associations between depression and CAD,
      nor between depression and cardiovascular risk factors. Coagulation and
      fibrinolytic factors showed no differences between patients with CAD and
      controls, but they were associated with several cardiovascular risk factors.
      Depression was not associated with coagulation and fibrinolytic factors. No
      associations were found either when both CAD and depression were taken into
      account. CONCLUSION: Our study gives no evidence that there is a significant
      relation among depression, CAD, and blood coagulation and fibrinolysis.

PMID- 18043300
TI  - Association of sports activities in leisure time and incident myocardial
      infarction in middle-aged men and women from the general population: the
      MONICA/KORA Augsburg cohort study.
AB  - BACKGROUND: To examine sex-specific associations between sports activities in
      leisure time and incident myocardial infarction (MI) in a representative
      population sample in Germany. DESIGN: Cohort study. METHODS: The study was based
      on 3501 men and 3475 women (aged 45-74 years) who participated in one of the
      three MONICA Augsburg surveys between 1984 and 1995 and were followed up until
      2002. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from
      Cox proportional hazard models. RESULTS: A total of 295 cases of incident MIs
      among men and 91 among women were registered during a median follow-up period of
      8.6 years. In both sexes, moderate and high level of sports activities in leisure
      time were associated with a reduced risk of incident MI after age and survey
      adjustment; the HRs of MIs associated with a moderate and high level of sports
      activities in leisure time were 0.68 (0.49-0.96), and 0.71 (0.50-0.99) for men
      and 0.42 (0.21-0.84), and 0.18 (0.04-0.74) for women. Further adjustment for
      other major coronary heart disease risk factors attenuated the HRs: in moderately
      and highly active men, the HRs were not significant anymore (HRs 0.78 and 0.84,
      respectively), but the HRs remained significantly reduced in moderately and
      highly active women (HR 0.49; 95% CI, 0.24-1.00 and HR 0.21; 95% CI, 0.05-0.87,
      respectively). CONCLUSION: Moderate or high levels of sports activities in
      leisure time are associated with a significantly reduced risk of MI in women, but
      not men from the general population.

PMID- 18043301
TI  - Stroke mortality and morbidity attributable to passive smoking in Germany.
AB  - BACKGROUND: Passive smoking is an established risk factor for coronary heart
      disease (CHD). Epidemiological studies suggest that passive smoking may also be
      associated with an increased risk of stroke. We estimate the burden of stroke due
      to passive smoking in Germany. METHODS: Frequency of passive smoking was derived
      from the German national health survey. Nonsmokers who reported exposure to
      environmental tobacco smoke (ETS) at home were considered for analyses. The
      relative risk for stroke and passive smoking was derived by means of a meta
      analysis from available cohort studies. We computed attributable risks for
      passive smoking and used data from official statistics to estimate stroke
      mortality due to ETS. Attributable stroke morbidity was calculated using the WHO
      Global-Burden-of-Disease approach. RESULTS: Passive smoking may account for 774
      stroke-related deaths and 1837 incident first ever strokes in Germany every year.
      More strokes owing to passive smoking occur among women (1248) than among men
      (589). The majority of strokes attributable to ETS happen at the age of 65-84
      years. CONCLUSION: ETS is a common exposure and stroke is a frequent disease.
      Though the relative risk of passive smoking on stroke mortality and morbidity is
      small, the impact on population health is substantial.

PMID- 18043302
TI  - Autonomic dysfunction: a link between depression and cardiovascular mortality?
      The FINE Study.
AB  - BACKGROUND: Depression is associated with an increased risk of cardiovascular
      diseases (CVD) in vascular patients as well as in the general population. We
      investigated whether autonomic dysfunction could explain this relationship.
      DESIGN: The Finland, Italy and The Netherlands Elderly (FINE) Study is a
      prospective cohort study. METHODS: Depressive symptoms were measured with the
      Zung Self-rating Depression Scale in 870 men, aged 70-90 years, free of CVD and
      diabetes in 1990. Resting heart rate was determined from a 15-30-s resting
      electrocardiogram in The Netherlands and Italy and as pulse rate in Finland. In
      addition, in The Netherlands, heart-rate variability (HRV) and QTc interval were
      determined. RESULTS: At baseline, depressive symptoms were associated with an
      increase in resting heart rate, and nonsignificantly with low HRV and prolonged
      QTc interval. After 10 years of follow-up, 233 (27%) men died from CVD.
      Prospectively, an increase in resting heart rate with 1 SD was associated with an
      increased risk of cardiovascular mortality [hazard ratio (HR), 1.22; 95%
      confidence interval (CI), 1.08-1.38]. In addition, low HRV (HR, 0.78; 95% CI,
      0.61-1.01) and prolonged QTc interval (HR, 1.28; 95% CI, 1.06-1.53) per SD were
      associated with cardiovascular mortality. The increased risk of depressive
      symptoms for cardiovascular mortality (HR, 1.38; 95% CI, 1.21-1.58) did not
      change after adjustments for several indicators of autonomic dysfunction.
      CONCLUSION: This study suggests that mild depressive symptoms are associated with
      autonomic dysfunction in elderly men. The increased risk of cardiovascular
      mortality with increasing magnitude of depressive symptoms could, however, not be
      explained by autonomic dysfunction.

PMID- 18043303
TI  - The effects of exercise training on insulin resistance in patients with coronary
      artery disease.
AB  - BACKGROUND: It is unclear whether the beneficial effects of habitual exercise on
      insulin resistance are due to concomitant weight loss, changes in diet or whether
      they are simply related to the transient effects of the last bout of exercise.
      Moreover, patients with coronary artery disease (CAD) have not been studied.
      DESIGN: Randomized controlled trial. METHODS: To determine the effects of
      exercise training on insulin resistance (i.e. low insulin sensitivity) in CAD
      patients without diabetes independent of changes in weight, diet or the effect of
      acute exercise, 29 patients were randomized to 12 weeks of supervised exercise
      training and 26 to usual activity. Insulin sensitivity was determined at 72 h
      following their last bout of exercise using the minimal model technique. Weight
      was held constant by adjusting caloric intake. RESULTS: Following the
      intervention, peak oxygen uptake increased by 0.18+/-0.14 l/min in the exercise
      training group, which was significantly higher (P<0.0001) than that in the usual
      activity group (0.02+/-0.14 l/min). Insulin sensitivity did not change
      significantly within or between groups during the study [exercise training 
      0.24+/-1.15 x 10(4)/min and usual activity 0.06+/-0.67 x 10(4)/min/(microU/ml)].
      CONCLUSIONS: Twelve weeks of moderate exercise training in the absence of weight
      loss did not result in significant change in insulin resistance in patients with
      CAD.

PMID- 18043304
TI  - Changes of cardiovascular risk factors and their implications in subsequent birth
      cohorts of older adults in Germany: a life course approach.
AB  - BACKGROUND: To examine lifetime patterns of cardiovascular risk factors and their
      implications in subsequent birth cohorts of older adults in Germany, who
      experienced very different political and socioeconomic conditions at various
      phases of their lives. DESIGN AND METHODS: Participants of the ESTHER study, a
      statewide cohort study conducted in Saarland, Germany, were categorized into four
      birth cohorts: 1925-1934, 1935-1939, 1940-1944, 1945-1952. At baseline, lifetime
      history of body weight, physical activity, smoking and drinking habits, and of
      physician-diagnosed diabetes mellitus were documented. The average BMI, the
      average number of hours of physical activity, prevalence of smoking and alcohol
      consumption between ages 20 and 50 years were assessed. The relative risks of a
      first diagnosis of diabetes mellitus before or at the age of 50 years by birth
      cohorts were assessed by multiple logistic regressions controlling for education
      and BMI at the age of 20. RESULTS: For both men and women, later birth cohorts
      had considerably worse lifestyle profiles. The frequency of diabetes mellitus up
      to the age of 50 years was much higher in the later than in the earlier cohorts.
      The increase was more pronounced among men than among women. CONCLUSION: Women
      and men reaching old age in the forthcoming years have more unfavourable lifetime
      risk factor profiles than earlier birth cohorts. These patterns might have
      substantial implications for the future burden of chronic disease.

PMID- 18043305
TI  - Health economic evaluation of controlled and maintained physical exercise in the
      prevention of cardiovascular and other prosperity diseases.
AB  - OBJECTIVES: Several studies and reports support the health benefits of frequent
      physical exercise, on the condition that this exercise is controlled and
      maintained. Given the scarce resources that can be spent on health and health
      care, the objective of this study was to evaluate the long-term health and
      economic outcomes of controlled and maintained physical exercise in a fitness
      setting. METHODS: A 25-year Markov model with a 12-month cycle-length and states
      representing diabetes, coronary heart disease, stroke, colon cancer and breast
      cancer was developed to predict cumulative costs and QALYs (quality adjusted life
      years) for three defined population cohorts, of different risk levels. Physical
      exercise was thereby compared with no intervention. Reduced risks associated with
      physical exercise, cost of diseases and loss of quality of life in case of
      disease were obtained from published literature. Costs were taken from a societal
      perspective; Belgium was selected as the setting. One way and probabilistic
      sensitivity analyses were carried out. RESULTS: For each of the cohorts, physical
      exercise is predicted to increase the QALYs and to offset a large part of the
      initial investment. The cost per QALY varies from 2000 to 15,000 Euro per QALY
      depending on the risk levels, which is better compared with a majority of
      secondary preventions that are currently publicly financed. CONCLUSION:
      Controlled and maintained physical exercise is projected to be cost-effective,
      which is likely to be explained by its simultaneous effect on several diseases
      and the associated weight loss, which affects quality of life positively.

PMID- 18043306
TI  - Intensity, but not duration, of physical activities is related to cognitive
      function.
AB  - BACKGROUND: Physical activity is thought to facilitate cognitive performance and
      to slow down the rate of age-related cognitive decline. This study aimed to
      investigate the association between the time spent on physical activity as well
      as the average intensity of these activities and cognitive function. DESIGN:
      Cross-sectional analysis. METHODS: Our study population comprised of 1927 healthy
      men and women aged 45-70 years in the Netherlands, examined from 1995 until 2000.
      Physical activity was assessed with an extensive questionnaire, and cognitive
      function by a neuropsychological test battery. RESULTS: Multivariate linear
      regression analysis showed that intensity of weekly physical activities is
      significantly positively associated with processing speed, memory, mental
      flexibility and overall cognitive function. No significant associations were
      observed between the time spent weekly on physical activities and the various
      cognitive domains. At the same time, variation in activities was significantly
      positively associated with speed, memory, mental flexibility and overall
      cognitive function. CONCLUSIONS: Average intensity of weekly physical activities
      and variation in activities are positively and significantly associated with
      cognitive performance on processing speed, memory and mental flexibility as well
      as performance on overall cognitive function.

PMID- 18043307
TI  - Safety and magnitude of changes in blood glucose levels following exercise
      performed in the fasted and the postprandial state in men with type 2 diabetes.
AB  - BACKGROUND: Information on the extent to which acute exercise reduces blood
      glucose levels (BGL) in type 2 diabetes is lacking. For this reason, the effects
      of exercise initiated at different preexercise BGL were assessed in men with type
      2 diabetes both in the fasted (FS) and the postprandial states (PS). DESIGN AND
      METHODS: Forty-three men with type 2 diabetes, 12 on diet alone and 31 on
      hypoglycaemic agents, completed a total of 1555 exercise sessions performed in
      the FS and 0-1, 1-2, 2-3, 3-4, 4-5, and 5-8 h in the PS. Capillary BGL were
      measured before and immediately after a 1h standardized aerobic exercise session
      on an ergocycle at 60% of VO2 peak. RESULTS: In the FS, there was an increase in
      postexercise BGL of 27+/-21% (mean+/-SD; P<0.001) when preexercise BGL was < or
      =6 mmol/l, no change when preexercise BGL were between 6 and 8 mmol/l, and a
      significant decrease of 12+/-13% when preexercise BGL were >8 mmol/l (P<0.001).
      In the PS, most exercise sessions were associated with significant decreases in
      BGL ranging between 18+/-17 and 50+/-12% (P<0.001), depending on the time
      interval between meals and the onset of exercise. Regarding the metabolic PS, the
      decline in BGL was most pronounced with high preexercise BGL. CONCLUSIONS: Our
      observations not only demonstrate that it was safe for middle-aged obese men with
      type 2 diabetes to exercise in the FS, but also show that the decrease in BGL
      during aerobic exercise was largely dependent on preexercise BGL.

PMID- 18043308
TI  - The anti-inflammatory effects of exercise training in patients with type 2
      diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus (DM) and chronic inflammation are strongly related
      to increased cardiovascular risk. The purpose of this study was to evaluate
      whether an aerobic training programme would ameliorate inflammatory and anti
      inflammatory markers in patients with type 2 DM. DESIGN: Interventional study.
      METHODS: A total of 60 overweight individuals with type 2 DM, but without
      vascular complications, were randomly assigned to either a 6-month aerobic
      exercise training programme (four times/week, 45-60 min/session), designated as
      exercise group, or to the control group. All participants were on an oral
      antidiabetic regimen and none was receiving lipid-lowering medications.
      Anthropometric parameters, cardiorespiratory fitness, glycaemic and lipid
      profiles, high sensitivity C-reactive protein (hs CRP), adiponectin, interleukin
      (IL)-10, IL-18, tumour necrosis factor (TNF)-alpha, insulin, reciprocal index of
      homoeostasis model assessment (HOMA-IR), body fat and blood pressure (BP) were
      measured at baseline and at the end of the study. RESULTS: In comparison with
      baseline and control group, exercise-treated patients improved glucose control,
      lipid profile, exercise capacity (VO2 peak) and exhibited decreased insulin
      resistance and systolic BP considerably (P<0.05). Plasma adiponectin, TNF-alpha
      and body weight changed slightly across treatment (P>0.05), whereas diastolic BP
      and fat mass tended to decrease (P=0.071 and 0.061, respectively). Exercise
      training reduced hs CRP (from 0.48+/-0.16 to 0.29+/-0.2 mg/dl; P=0.04) and IL-18
      (from 315.19+/-122.76 to 203.77+/-96.02 pg/ml; P=0.02). Moreover, exercise
      provided anti-inflammatory protection through IL-10 increment (P=0.039) and IL
      18/IL-10 ratio downregulation (P=0.014). In multiple regression analysis,
      alteration in IL-18 was independently correlated with hs CRP and VO2 peak changes
      (P<0.05). CONCLUSION: Aerobic exercise training without significant weight loss
      improves metabolic profile and exerts anti-inflammatory effects in patients with
      type 2 DM.

PMID- 18043309
TI  - Deprivation status and mid-term change in blood pressure, total cholesterol and
      smoking status in middle life: a cohort study.
AB  - BACKGROUND: Individuals of lower socioeconomic status have an adverse
      cardiovascular disease risk factor profile. We examined whether deprivation
      status influences within-individual change over time in blood pressure (BP),
      cholesterol and smoking status during middle life. METHODS: Records of
      participants of a primary care-based cardiovascular disease risk factor screening
      programme who were aged 35-55 years and had a first screening episode between
      1989 and 1993 and a subsequent screening episode, were analysed. Deprivation
      status was defined using quintiles of the Townsend score. Using regression, mean
      annual change in BP, and total cholesterol was calculated for each deprivation
      group; and the effect of deprivation group status was examined. The probability
      of quitting smoking was also examined by deprivation group. RESULTS: Of all
      participants, 13,812 (72.1%) men and 16 932 (77.0%) women had complete follow-up
      (i.e. two screening episodes). Mean annual increase in systolic BP was
      significantly greater with increasing deprivation group [by +0.24 and +0.28
      mmHg/incremental deprivation group in men and women, respectively (95% confidence
      interval: +0.09 to +0.39 men, and +0.13 to +0.42 women)]. Deprivation status did
      not influence change in cholesterol (P=0.620, men, P=0.289, women). The
      probability of quitting smoking was significantly greater with increasing
      deprivation group in women [odds ratio 1.06 (95% confidence interval: 1.01
      1.12)], but no effect was observed in men (P=0.389). DISCUSSION: The results are
      suggestive of a 'mixed' picture of widening (e.g. systolic and diastolic BP) as
      well as narrowing (e.g. smoking in women) socioeconomic inequalities in
      cardiovascular risk factor inequalities.

PMID- 18043312
TI  - Differentiation of monocytes into CD1a- dendritic cells correlates with disease
      progression in HIV-infected patients.
AB  - Monocyte differentiation into dendritic cells (DCs) depends on microenvironmental
      conditions. In this study, the capacity of human monocytes to differentiate into
      mature DCs and their ability to induce an antiviral immune response was
      investigated in HIV-infected patients. In healthy subjects, monocytes
      differentiate into CD1a+ DCs in the presence of granulocyte macrophage colony
      stimulating factor and interleukin (IL)-4 and matured in the presence of
      lipopolysaccharide. Here, we found that in 30% and 45% of HIV-infected white and
      African subjects, respectively, monocytes gave rise to a homogeneous CD1a* DC
      population. In the patients who gave rise only to the CD1a* DCs, this population
      spontaneously produced IL-10 but not IL-12, and induced a T helper 2-like immune
      response when cultured with human T cells isolated from cord blood mononuclear
      cells. In patients with monocytes differentiated into CD1a* DCs, a high
      percentage of HIV-specific CD4 T cells producing IL-4 were seen in the peripheral
      blood. Furthermore, differentiation of monocytes into DCs with CD1a* phenotype
      correlated with low CD4 T-cell counts and high viral loads in HIV-infected
      subjects. These results suggest that the differentiation of monocytes into CD1a*
      DCs may be a phenotypic marker associated with progression of the disease.

PMID- 18043311
TI  - Bystander effects: children who escape infection but not harm.

PMID- 18043313
TI  - Chinese pediatric highly active antiretroviral therapy observational cohort: a 1
      year analysis of clinical, immunologic, and virologic outcomes.
AB  - BACKGROUND: Few data are available on the outcomes of pediatric antiretroviral
      therapy (ART) in the developing world. METHODS: Eighty-three children were
      followed prospectively in China from July 2005 to August 2006 and received
      (zidovudine or stavudine) plus lamivudine plus (nevirapine or efavirenz).
      RESULTS: Fifty-one children were ART naive at enrollment, and 32 were ART
      experienced. After 12 months, median weight increased by 0.3 weight for age z
      score, median CD4 count increased from 116 to 340 cells/mm (P < 0.0001), and
      median viral load decreased from 5.53 to <2.60 log10 copies/mL (P < 0.0001) in
      the previously ART-naive children. In the ART-experienced children, median CD4
      count increased from 193 to 318 cells/mm (P = 0.13), despite little change in
      median viral load (4.85 to 4.58 log10 copies/mL; P = 0.83). The viral load was
      <400 copies/mL in 55% of the previously ART-naive children and in 16% of the ART
      experienced children. CONCLUSIONS: Weight and CD4 cell counts improved, and more
      than half of previously ART-naive patients had undetectable viral loads at 1
      year. Future efforts should focus on improved virologic suppression through
      improved adherence and access to second-line regimens.

PMID- 18043314
TI  - Maternal disease stage and child undernutrition in relation to mortality among
      children born to HIV-infected women in Tanzania.
AB  - OBJECTIVE: To examine whether maternal HIV disease stage during pregnancy and
      child malnutrition are associated with child mortality. DESIGN: Prospective
      cohort study in Tanzania. METHODS: Indicators of disease stage were assessed for
      939 HIV-infected women during pregnancy and at delivery, and children's
      anthropometric status was obtained at scheduled monthly clinic visits after
      delivery. Children were followed up for survival status until 24 months after
      birth. RESULTS: Advanced maternal HIV disease during pregnancy (CD4 count <350
      vs. >or=350 cells/mm) was associated with increased risk of child mortality
      through 24 months of age (hazard ratio [HR] = 1.74, 95% confidence interval [CI]:
      1.32 to 2.30). CD4 count <350 cells/mm was also associated with an increased risk
      of death among children who remained HIV-negative during follow-up (HR = 2.00,
      95% CI: 1.36 to 2.94). Low maternal hemoglobin concentration and child
      undernutrition were related to an increased risk of mortality in this cohort of
      children. CONCLUSIONS: Low maternal CD4 cell count during pregnancy is related to
      increased risk of mortality in children born to HIV-infected women. Care and
      treatment for HIV disease, including highly active antiretroviral therapy to
      pregnant women, could improve child survival. Prevention and treatment of
      undernutrition in children remain critical interventions in settings with high
      HIV prevalence.

PMID- 18043315
TI  - Importance of baseline prognostic factors with increasing time since initiation
      of highly active antiretroviral therapy: collaborative analysis of cohorts of HIV
      1-infected patients.
AB  - BACKGROUND: The extent to which the prognosis for AIDS and death of patients
      initiating highly active antiretroviral therapy (HAART) continues to be affected
      by their characteristics at the time of initiation (baseline) is unclear.
      METHODS: We analyzed data on 20,379 treatment-naive HIV-1-infected adults who
      started HAART in 1 of 12 cohort studies in Europe and North America (61,798
      person-years of follow-up, 1844 AIDS events, and 1005 deaths). RESULTS: Although
      baseline CD4 cell count became less prognostic with time, individuals with a
      baseline CD4 count <25 cells/microL had persistently higher progression rates
      than individuals with a baseline CD4 count >350 cells/microL (hazard ratio for
      AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio =
      2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were
      persistently higher in individuals who had experienced an AIDS event before
      starting HAART. Individuals with presumed transmission by means of injection drug
      use experienced substantially higher rates of AIDS and death than other
      individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0;
      mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting
      HAART). CONCLUSIONS: Compared with other patient groups, injection drug users and
      patients with advanced immunodeficiency at baseline experience substantially
      increased rates of AIDS and death up to 6 years after starting HAART.

PMID- 18043316
TI  - HIV prevalence and incidence in rural Tanzania: results from 10 years of follow
      up in an open-cohort study.
AB  - BACKGROUND: Tanzanian antenatal clinic surveillance data suggest stabilizing HIV
      levels. Data from an open cohort in northern Tanzania provide robust estimates of
      prevalence and incidence. METHODS: Between 1994 and 2004, 19 rounds of household
      based demographic surveillance and 4 rounds of individually linked HIV serologic
      surveys were conducted. Longitudinal knowledge of individuals' testing histories
      is used to allow for effects of selective participation on prevalence estimates;
      multiple imputation procedures allow for interval censoring effects on incidence.
      RESULTS: A total of 16,820 adults donated blood for HIV testing in at least 1 of
      4 serologic surveys. HIV prevalence increased steadily from 6.0% in 1994/1995 to
      8.3% in 2000/2001, leveling out thereafter. HIV incidence increased sharply from
      0.8% in 1994 to 1997 to 1.2% per thousand in 1997 to 2000, remaining high (1.1%)
      in 2000 to 2003. In roadside areas, incidence fell in the last interval,
      especially among women, but in remote rural areas, incidence rose slightly.
      CONCLUSIONS: HIV spread is continuing in rural areas, suggesting a need for more
      intensive HIV prevention efforts and antiretroviral interventions. The leveling
      off in prevalence is attributable to a combination of high mortality among HIV
      infected persons and a slight decrease in incidence in roadside villages.

PMID- 18043317
TI  - HIV-1 infection in patients referred for malaria blood smears at government
      health clinics in Uganda.
AB  - BACKGROUND: HIV is associated with an increased incidence of malaria in adult
      African populations. In children, the relationship between HIV and malaria is
      less clear. We investigated the relationship between malaria and HIV-1 infection
      among adults and children referred for malaria blood smears at government health
      clinics in Uganda. METHODS: This was a cross-sectional study in which 1000
      consecutive patients referred for malaria blood smears over the course of 1 to 2
      months at each of 7 government clinics (N = 7000) were tested for HIV-1 from
      dried blood spots using enzyme-linked immunosorbent assay (ELISA) screening and
      nucleic acid-based confirmatory testing. Risk factors for HIV-1 infection were
      identified using multivariate logistic regression. RESULTS: Among 4467 children
      aged 16 years or younger, 77 (1.7%) were HIV-1 infected. Of 2533 adults, 270
      (10.7%) were HIV-1 infected. In children, having a negative malaria blood smear
      was associated with higher odds of HIV-1 infection (odds ratio [OR] = 1.90, 95%
      confidence interval [CI]: 1.18 to 3.06) after controlling for age and gender. In
      adults, having a positive malaria blood smear was moderately associated with
      higher odds of HIV-1 infection (OR = 1.41, 95% CI: 1.01 to 1.97) after
      controlling for age and gender. CONCLUSIONS: In Ugandans evaluated for suspected
      malaria, associations between malaria smear results and HIV infection differed
      between children and adults. Although further operations research is needed, our
      results suggest that counseling and testing for HIV may be of particular
      importance in children suspected of malaria but with negative malaria smears and
      in adults with positive malaria smears.

PMID- 18043318
TI  - Risk factors for herpes simplex virus type 2 and HIV among women at high risk in
      northwestern Tanzania: preparing for an HSV-2 intervention trial.
AB  - OBJECTIVES: To determine prevalence of and risk factors for herpes simplex virus
      type 2 (HSV-2) and HIV among women being screened for a randomized, controlled
      trial of HSV suppressive therapy in northwestern Tanzania. METHODS: Two thousand
      seven hundred nineteen female facility workers aged 16 to 35 were interviewed and
      underwent serological testing for HIV and HSV-2. Factors associated with HSV-2
      and HIV in women aged 16 to 24 were examined using logistic regression to
      estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: HSV-2
      seroprevalence was 80%, and HIV seroprevalence was 30%. Among women aged 16 to
      24, both infections were significantly and independently associated with older
      age, being a bar worker, working at a truck stop, and having more lifetime sexual
      partners. HSV-2 infection was also associated with lower socioeconomic status,
      increased alcohol intake, younger age at first sex, inconsistent condom use, and
      vaginal douching. There was a strong association between the 2 infections after
      adjustment for other factors (OR = 4.22, 95% CI: 2.6 to 6.9). CONCLUSIONS: Female
      facility workers in northwestern Tanzania are vulnerable to HSV-2 and HIV
      infections. Programs designed to increase safer sexual behavior and reduce
      alcohol use could be effective in reducing HSV-2 incidence and, in turn, HIV
      infection. This is a suitable population for an HSV suppressive therapy trial.

PMID- 18043319
TI  - Circumcision status and HIV infection among Black and Latino men who have sex
      with men in 3 US cities.
AB  - OBJECTIVE: To examine characteristics of circumcised and uncircumcised Latino and
      black men who have sex with men (MSM) in the United States and assess the
      association between circumcision and HIV infection. METHODS: Using respondent
      driven sampling, 1154 black MSM and 1091 Latino MSM were recruited from New York
      City, Philadelphia, and Los Angeles. A 45-minute computer-assisted interview and
      a rapid oral fluid HIV antibody test (OraSure Technologies, Bethlehem, PA) were
      administered to participants. RESULTS: Circumcision prevalence was higher among
      black MSM than among Latino MSM (74% vs. 33%; P < 0.0001). Circumcised MSM in
      both racial/ethnic groups were more likely than uncircumcised MSM to be born in
      the United States or to have a US-born parent. Circumcision status was not
      associated with prevalent HIV infection among Latino MSM, black MSM, black
      bisexual men, or black or Latino men who reported being HIV-negative based on
      their last HIV test. Further, circumcision was not associated with a reduced
      likelihood of HIV infection among men who had engaged in unprotected insertive
      and not unprotected receptive anal sex. CONCLUSIONS: In these cross-sectional
      data, there was no evidence that being circumcised was protective against HIV
      infection among black MSM or Latino MSM.

PMID- 18043320
TI  - Subclinical mastitis, cell-associated HIV-1 shedding in breast milk, and breast
      feeding transmission of HIV-1.
AB  - BACKGROUND: Mastitis has been identified as a risk factor for mother-to-child
      transmission (MTCT) of HIV-1 through breast-feeding. It is unclear whether this
      association is mediated by increased cell-free virus (CFV) versus cell-associated
      virus (CAV) HIV shedding in breast milk. METHODS: We examined the risk of MTCT
      associated with subclinical mastitis and the relation between mastitis and CFV or
      CAV shedding in breast milk. Fifty-nine women who transmitted HIV through breast
      feeding (cases) were individually matched to 59 nontransmitting controls nested
      in a cohort from Tanzania. For each case, we selected a milk specimen obtained
      before the infant's first positive test to quantify sodium (Na) and potassium (K)
      and measure CFV and CAV concentrations. Controls were matched on the child's age
      at the time of sample collection. RESULTS: Women with a breast milk Na/K ratio
      suggestive of mastitis (>1.0) had an 11-fold greater odds of transmission (95%
      confidence interval [CI]: 1.2 to 98.1), compared to women with a Na/K <or=0.6,
      after adjusting for maternal CD4 cell count and vitamin A supplementation.
      Although mastitis was positively related to both CFV and CAV shedding in breast
      milk, only the association with the latter was strong and statistically
      significant. CONCLUSION: Increased cell-associated HIV-1 shedding in breast milk
      could mediate the association between mastitis and MTCT.

PMID- 18043321
TI  - Contribution of HIV to mortality among injection drug users in the era of HAART.

PMID- 18043322
TI  - Response to "Persistence of Neuropsychologic Deficits Despite Long-Term Highly
      Active Antiretroviral Therapy in Patients With HIV-Related Neurocognitive
      Impairment".

PMID- 18043324
TI  - The presence of a caregiving relative implicated in the administration of
      antiretroviral drug administration improves virologic response.

PMID- 18043327
TI  - Conversations in Ethics.

PMID- 18043328
TI  - Development of a standardized medication assistant curriculum.

PMID- 18043329
TI  - The Patient Self-determination Act: has it reached the end of its life?
AB  - The Patient Self-determination Act requires that patients be informed in writing
      of their right to accept or refuse treatment and the right to an advance
      directive. For the past 15 years, hospitals have been providing these written
      materials, yet advance directives are still not adequately directing end-of-life
      care. Barriers and facilitators to implementation of this law are discussed, as
      well as the role of nursing management in meeting its true intent.

PMID- 18043331
TI  - Nurses' perceptions of content and delivery style of bioterrorism education.
AB  - The long-term purpose of this study was to assess the effectiveness of a problem
      solving computerized bioterrorism education and training (CBET) program compared
      with a standard bioterrorism education and training (SBET) program. The content
      and delivery preferences of nurses employed in two major hospitals in Los Angeles
      and San Diego that would be relevant to the design of the SBET and CBET scenarios
      were assessed. During the focus groups, nurses also considered culturally
      sensitive delivery aspects. Notable findings from the focus groups are discussed
      in this study. Recommendations based on these findings are proposed as this
      project moves into subsequent phases.

PMID- 18043333
TI  - Clinical staff development: planning and teaching for desired outcomes.
AB  - Nursing staff development educators facilitate learning activities to promote
      learner retention of knowledge: factual, conceptual, procedural, and meta
      cognitive. The Revised Bloom's Taxonomy provides a modern framework for the
      cognitive process dimension of knowledge and guides the nursing educator in
      planning activities that will assure learner progress along the learning
      continuum.

PMID- 18043335
TI  - Post-diagnostic cardiac catheterization: development and evaluation of an
      evidence-based standard of care.
AB  - The purpose of this article is to describe one process for the development and
      evaluation of an evidence-based standard of care for inpatients undergoing a
      diagnostic cardiac catheterization. As the volume of cardiac catheterizations
      increases, with more high-risk patients and with new methods to achieve
      hemostasis, an evidence-based standard of care for the post-diagnostic cardiac
      catheterization patient needs to be developed to ensure positive clinical
      outcomes. Clinical educators are in a position to affect nursing practice and can
      provide the impetus for implementing evidence-based standards of care.

PMID- 18043336
TI  - Identifying the educational needs of nursing staff: the role of the clinical
      nurse specialist in perinatal nursing.
AB  - One of the priorities of the perinatal clinical nurse specialist is the
      identification of educational needs. This article describes the experience of 2
      perinatal clinical nurse specialists and presents various methods for identifying
      the educational needs of perinatal nursing staff in the hospital setting.

PMID- 18043337
TI  - Staff nurses writing for their peers: development of self-learning modules.
AB  - Self-learning modules (SLMs) provide an educational format that is easily
      portable and can be incorporated into the nurse's day at the nurse's convenience.
      Self-learning modules are a flexible teaching modality than can enhance not only
      nurse's knowledge and skill but also the unit's educational programs.
      Incorporating the bedside nurses in the development of SLMs has provided an
      opportunity for staff to work on writing skills, produce a professional product,
      and receive contact hours. The use of author guidelines, content expert and peer
      review is described in detail.

PMID- 18043338
TI  - A mock trial approach: nursing competency program.
AB  - The purpose of developing a mock trial was to promote an innovative, engaging,
      and stimulating program where the learner experiences and demonstrates knowledge
      related to predetermined objectives for a yearly nursing competency program.

PMID- 18043339
TI  - The moved to evidenced-based practice from a clinical nursing question.
AB  - Registered nurses on a medical unit questioned whether current practice
      adequately met the emotional needs of patients with chronic obstructive pulmonary
      disease hospitalized for acute dyspnea. The unit's education committee surveyed
      nursing staff regarding priority nursing activities during dyspneic episodes.
      After discussion with staff development educators, several registered nurses met
      with the center's nurse researcher, formed a research team, and designed a
      descriptive study. Findings of the study gave evidence for clinical practice
      change and revision of care guidelines.

PMID- 18043340
TI  - Sail training: an innovative approach to graduate nurse preceptor development.
AB  - A 1-day sail-training program that aims to increase graduate nurse preceptor
      skills was evaluated. Preliminary results suggest that this experiential learning
      is an effective way to develop graduate nurse preceptors. Awareness of graduate
      nurses' needs has been heightened, and skills in clinical teaching have been
      developed. It is indicated from the limited results that the outcomes are
      sustained over time, but further evaluation is needed.

PMID- 18043341
TI  - Staff development story.

PMID- 18043342
TI  - Instant teaching tools.

PMID- 18043343
TI  - National Nursing Staff Development Organization.

PMID- 18043344
TI  - Preoperative evaluation of local invasion and metastatic lymph nodes of
      colorectal cancer and mesenteric vascular variations using multidetector-row
      computed tomography before laparoscopic surgery.
AB  - OBJECTIVE: To evaluate local invasion and lymph nodes metastasis of colorectal
      cancer and mesenteric vascular variations using multidetector-row computed
      tomography (MDCT) before laparoscopic colorectal surgery. METHODS: Fifty-one
      patients with colorectal cancer underwent MDCT. The evaluation items were as
      follows: (1) local invasion; (2) detected lymph nodes evaluated by short-axis
      diameter, long-axis diameter, short/long axis diameter ratio, and computed
      tomography (CT) attenuation; and (3) visualization of mesenteric artery and vein
      by 3-dimensional-CT angiography. RESULTS: First, in the evaluation of local
      invasion, overall accuracy was 94.1%. Second, the point of 0.8 or greater in
      short/long-axis diameter ratio was best index for the diagnosis of metastatic
      lymph nodes. Using this index, the accuracy of the diagnosis per node was 80.5%.
      Third, 3-dimensional-CT angiography correctly demonstrated variations of the
      mesenteric artery and vein. CONCLUSIONS: The MDCT was effective for evaluation of
      local invasion and lymph nodes metastasis of colorectal cancer and mesenteric
      vascular variations before laparoscopic surgery.

PMID- 18043345
TI  - Comparison of 2 contrast materials with different iodine concentrations in 3
      dimensional computed tomography angiography of the hepatic artery at multi
      detector-row computed tomography: a randomized study.
AB  - OBJECTIVE: To investigate differences in visual evaluation of the hepatic
      arteries and contrast enhancement of the vessels and liver at 3-dimensional (3D)
      computed tomography (CT) angiography by 2 different concentrations of contrast
      materials. METHODS: Eighty patients were randomly assigned into groups A and B
      receiving contrast materials with iodine concentrations of 300 and 370 mg/mL,
      respectively. The total iodine load (600 mg/kg), iodine injection time (25
      seconds), and saline flush time (10 seconds) were identical. RESULTS: Seventy-two
      patients were evaluable. There were no differences between the 2 groups in visual
      evaluation of the hepatic arteries at 3D CT angiography. Contrast enhancement of
      the aorta at the late arterial phase and the liver at the portal phase was
      significantly higher in group B than in group A, but otherwise, there were no
      differences. Enhancement of the aorta and portal vein was higher in women than in
      men at some phases. CONCLUSIONS: With the same iodine dose and injection time,
      the concentration of contrast materials did not seem to be important in obtaining
      optimal images at 3D CT angiography of the hepatic artery.

PMID- 18043346
TI  - Comparison between 3-T magnetic resonance imaging and multi-detector row computed
      tomography for the preoperative evaluation of rectal cancer.
AB  - OBJECTIVE: To compare prospectively between 3-T magnetic resonance imaging (MRI)
      and multidetector row computed tomography (MDCT) for the local staging of rectal
      cancer. MATERIALS AND METHODS: During a recent 8-month period, both 3-T MRI with
      a phased array coil and MDCT scanner were used to preoperatively examine 31
      consecutive patients. Preoperatively, the 3 experienced reviewers independently
      assessed the MRI and MDCT findings for the depth of tumor invasion into the
      rectal wall (T). Regional lymph node metastasis (N) was assessed by the 3
      reviewers working in consensus. For T staging, we used a modified T staging
      (<or=T2, T3, and T4 staging). The results of the MRI and MDCT findings were
      compared based on the diagnosis of the resected specimens. RESULTS: At
      histopathology, T1 was identified in 8 patients, T2 in 6, and T3 in 17 patients.
      The sensitivity, specificity, and accuracy for T2 staging or less between MRI and
      MDCT were 93% and 79%, 88% and 76%, and 91% and 77%, respectively. The
      sensitivity, specificity, and accuracy for T3 between MRI and MDCT were 92% and
      73%, 93% and 83%, and 92% and 78%, respectively; there was a statistically
      significant difference for the T2 and T3 staging or less (P < 0.01). For N
      staging, MRI and CT can predict accurately in 88% and 77%, respectively (P >
      0.05). CONCLUSIONS: For local staging of rectal cancer, 3-T MRI is more accurate
      than MDCT for determining the depth of tumor invasion and the extent of lymph
      node metastasis.

PMID- 18043347
TI  - Pancreatic cystic lesions: discrimination accuracy based on clinical data and
      high resolution CT features.
AB  - OBJECTIVE: To determine the accuracy of high-resolution computed tomography in
      discriminating among pancreatic cystic lesions with and without clinical history.
      METHODS: Multiphasic high-resolution computed tomographic scans of 100 proven
      cystic pancreatic lesions were retrospectively reviewed by 2 blinded imagers.
      Before and after a history of pancreatitis was revealed, readers classified
      lesions as either nontumor-related or tumor-related. Reviewers also classified
      lesions as benign or malignant and finally categorized each lesion as serous,
      mucinous, or other lesion. Diagnostic performance parameters for classification
      were calculated for each reader with and without history. RESULTS: Sixty-two
      lesions were tumor-related and 38 were not. Accuracy for classifying tumor
      related from unrelated cysts for both reviewers increased (83%-92%, 85%-91%) when
      unblinded to pancreatitis history. Specificity also significantly increased (66%
      88% and 84%) for both reviewers. CONCLUSIONS: Pancreatic-phase computed
      tomography enabled more than 80% accuracy in discriminating between tumor-related
      and unrelated lesions and increased with information of pancreatitis history.

PMID- 18043348
TI  - Detection of recurrent ovarian cancer at MRI: comparison with integrated PET/CT.
AB  - OBJECTIVE: To compare the diagnostic performances of magnetic resonance imaging
      (MRI) and positron emission tomography/computed tomography (PET/CT) for the
      detection of recurrent ovarian tumor. METHODS: Thirty-six patients who underwent
      primary cytoreductive surgery for ovarian carcinoma received both MRI and PET/CT
      for the evaluation of ovarian tumor recurrence. Recurrent ovarian tumors in
      abdomen and pelvis were classified based on site as follows: (1) local pelvic
      recurrence, (2) peritoneal lesion, (3) lymph nodal metastasis, and (4) distant
      metastasis. Patient-based and lesion-based analyses were retrospectively
      performed with the aim of detecting tumor recurrence. For the detection of
      recurrent ovarian tumors, we compared patient-based and lesion-based diagnostic
      accuracies of these 2 modalities using the McNemar test. RESULTS:
      Histopathologic, clinical, and radiological follow-up findings revealed recurrent
      ovarian tumors in 35 sites of 22 patients. These 35 sites consisted of local
      pelvic recurrence (n = 15), peritoneal lesions (n = 14), lymph nodal metastasis
      (n = 4), and abdominal wall metastasis (n = 2). In detecting recurrent ovarian
      tumor, patient-based sensitivity and the accuracy of PET/CT and MRI were 73% and
      91% (P < 0.05), and 81% and 89% (P > 0.05), respectively. In addition, overall
      lesion-based sensitivity of PET/CT and MRI were 66% and 86%, respectively (P <
      0.05). In detecting peritoneal lesions, overall lesion-based sensitivity and
      accuracy of PET/CT and MRI for peritoneal lesions were 43% and 86%, and 75% and
      94%, respectively (P < 0.05). CONCLUSIONS: Magnetic resonance imaging is more
      sensitive than PET/CT for detecting local pelvic recurrence and peritoneal
      lesions of recurrent ovarian tumors.

PMID- 18043349
TI  - Cine magnetic resonance imaging evaluation of peristalsis of small bowel with
      longitudinal ulcer in Crohn disease: preliminary results.
AB  - OBJECTIVE: To evaluate peristalsis of the small bowel with a longitudinal ulcer
      in Crohn disease using cine magnetic resonance imaging (MRI). METHODS: Fifteen
      patients with suspected or diagnosed Crohn disease were examined by cine MRI
      using a multislice and multiphase method. Inclusion criteria were pathological
      evidence of Crohn disease and confirmation of longitudinal ulceration in the
      small bowel by ileocolonoscopy, single- or double-contrast radiography of the
      small bowel, or surgery. Six of these patients were included in this study. Cine
      MRI findings of the small bowels were retrospectively reviewed by 2 radiologists.
      RESULTS: Asymmetric involvement or mesenteric rigidity with antimesenteric
      flexibility was seen in all patients by cine MRI. This finding was not seen in
      normal small bowel segments. A combination of ileocolonoscopy and contrast
      radiography detected longitudinal ulcers in 5 of the 6 patients, and surgery
      revealed ulceration in the remaining patient. CONCLUSIONS: Cine MRI was a
      feasible approach for detecting a longitudinal ulcer in small-bowel Crohn
      disease.

PMID- 18043350
TI  - Reduced perfusion reserve in Leukoaraiosis demonstrated using acetazolamide
      challenge 123I-IMP SPECT.
AB  - OBJECTIVE: We examined the relationship between the perfusion reserve as measured
      by acetazolamide (ACZ)-challenge N-isopropyl-I-123-p-iodoamphetamine (IMP)-single
      photon emission computed tomography (SPECT) and the degree of leukoaraiosis (LA)
      as estimated using magnetic resonance imaging. METHODS: In 51 patients receiving
      IMP-SPECT with the resting state and ACZ challenge, the unaffected cerebral
      hemispheres were included in the present study. Mean cerebral blood flow (CBF) in
      the resting state and ACZ reactivity were acquired. Absolute CBF value and ACZ
      reactivity were compared among patients with LA grades 0, 1, and 2. The
      relationship between mean age and LA grade was also assessed. RESULTS: No
      significant difference in the absolute CBF value in the resting state was
      observed among the 3 LA groups. Although vasoreactivity in LA grade 0 did not
      differ from that in grade 1, vasoreactivity in LA grade 2 was significantly lower
      (P < 0.05) than that in grades 0 or 1. CONCLUSIONS: The perfusion reserve is
      impaired in advanced LA.

PMID- 18043351
TI  - Clinical implications of increased fractional anisotropy in meningitis associated
      with brain abscess.
AB  - AIM: To look for the clinical implications of increased cortical fractional
      anisotropy (FA) in meningitis patients associated with brain abscess. MATERIAL
      AND METHODS: Diffusion tensor imaging was performed in 10 patients of meningitis
      associated with brain abscess and 10 controls. The region of interest analysis
      was performed to calculate FA and mean diffusivity values from the abscess cavity
      and cortical regions of patients (enhancing and nonenhancing meninges on
      postcontrast T1-weighted images) and controls. RESULTS: Significantly increased
      FA values with no change in mean diffusivity values were found in enhancing (FA =
      0.113 +/- 0.023, P = 0.000) as well as nonenhancing (FA = 0.085 +/- 0.009, P =
      0.000) cortical region of patients compared with controls (FA = 0.067 +/- 0.010).
      CONCLUSIONS: Increased FA values in the enhancing as well as nonenhancing
      cortical regions suggest diffuse inflammatory activity in the pia-arachnoid in
      meningitis patients. It also suggests that FA may be a better indicator of active
      and diffuse meningeal inflammation than postcontrast T1-weighted images.

PMID- 18043352
TI  - Magnetic resonance imaging of individual cerebral perfusion territories improves
      the diagnosis of embolic stroke.
AB  - This case study demonstrates the feasibility and diagnostic value of the oblique
      plane arterial spin labeling method to visualize individual perfusion territories
      in a patient with embolic stroke. The perfusion territories obtained with this
      technique differed significantly from the standard anatomical situation. Imaging
      findings suggested that all acute embolic lesions in both hemispheres had arisen
      from one symptomatic internal carotid artery stenosis.

PMID- 18043353
TI  - Discrepancy between the dynamic computed tomography and T2 magnetic resonance
      perfusion imaging in brain tumors: a report of 2 cases.
AB  - In this report, we separately performed dynamic computed tomographic perfusion
      and dynamic susceptibility contrast-T2 magnetic resonance perfusion imaging on 2
      cases of brain tumors (one was a glioblastoma, and the other was a central
      neurocytoma). Between the 2 methods, we saw the discrepancy in values of cerebral
      blood volume and cerebral blood flow, differences in location of the maximal
      cerebral blood volume, and regions with abnormal increased cerebral blood flow
      besides the solid part of the tumors. Both differences and similarities of the 2
      techniques with their advantages and pitfalls were analyzed in detail. The
      developing trends in the near future were also discussed.

PMID- 18043354
TI  - Corticospinal tract restoration: combined study of diffusion tensor tractography,
      functional MRI, and transcranial magnetic stimulation.
AB  - We tried to demonstrate the restoration of corticospinal tract in a patient with
      intracerebral hemorrhage, using diffusion tensor tractography and functional
      magnetic resonance imaging, and transcranial magnetic stimulation. Transcranial
      magnetic stimulation demonstrated the corticospinal tract had been spared since
      subacute stage. Diffusion tensor tractography and functional magnetic resonance
      imaging showed that the corticospinal tract that was displaced by a hematoma had
      been restored. These combined modalities would be helpful in elucidating the
      state and change of corticospinal tract.

PMID- 18043355
TI  - Multidetector computed tomography for the detection of left atrial appendage
      thrombus: a comparative study with transesophageal echocardiography.
AB  - OBJECTIVE: To determine the diagnostic performance of multidetector computed
      tomography (MDCT) for the detection of left atrial appendage (LAA) thrombus as
      compared with transesophageal echocardiography. METHODS: Multidetector computed
      tomography was evaluated in 43 patients qualitatively for the presence or absence
      of a filling defect in the LAA and compared with transesophageal
      echocardiography. Additionally, a ratio of the mean computed tomographic
      attenuation in the LAA apex to the mean computed tomographic attenuation in the
      aortic root was used for quantitative evaluation. RESULTS: A filling defect
      visualized in the LAA by MDCT corresponded to a sensitivity of 70% (7/10), a
      specificity of 82% (27/33), and a negative predictive value of 90% (27/30) for
      detection of LAA thrombus. When using quantitative parameters, MDCT demonstrated
      a sensitivity of 80% (8/10), a specificity of 73% (24/33), and a negative
      predictive value of 92% (24/26). Multidetector computed tomography was not able
      to differentiate LAA thrombus from spontaneous echo contrast by either visual
      evaluation or by quantitative parameters. CONCLUSIONS: Multidetector computed
      tomography remains limited for the detection of LAA thrombus. However, a subgroup
      of patients at very high risk for LAA thrombus may benefit from the high negative
      predictive value of cardiac MDCT.

PMID- 18043356
TI  - Assessment of coronary stents using 40-detector row CT: comparison with 16
      detector row CT in vitro.
AB  - OBJECTIVE: To evaluate the performance of 40-detector row computed tomography
      (CT) in the assessment of coronary stents in comparison with 16-detector row CT.
      METHODS: A total of 6 vascular models (3 models without stenosis and 3 with
      stenosis) using 3 types of stent (Bx-Velocity, Express2, and Driver) with an
      approximately 3.5-mm inner diameter filled with contrast material (450 Hounsfield
      units) were scanned with 2 computed tomographic scanners (collimation, 16 x 0.75
      and 40 x 0.625 mm). We evaluated the in-stent stenosis visually for the 6
      vascular models in 4 orientations (0, 30, 60, and 90 degrees) to the z-axis of
      the scanner. We evaluated attenuation values of the stent lumen of the 3 patent
      models in the 4 orientations. The average and standard deviation of the luminal
      attenuation values were assessed to evaluate the degree of blooming and streak
      artifacts. RESULTS: The visualization of the stent lumen of the vascular models
      at 90 degrees was improved using 40-detector row CT. For all the 3 stents, the
      average luminal attenuations values using 40-detector row CT were significantly
      lower than those using 16-detector row CT in all orientations. For all the 3
      stents, the standard deviations of the luminal computed tomographic attenuation
      using 40-detector row CT were significantly smaller than those using 16-detector
      row CT in the 4 orientations to the z-axis except for Express 2 at 0 degrees.
      CONCLUSIONS: The visualization of coronary stents is improved by the use of 40
      detector row CT with reduced blooming and streak artifacts.

PMID- 18043357
TI  - Enhancement performance of a 64-slice triple rule-out protocol vs 16-slice and 10
      slice multidetector CT-angiography protocols for evaluation of aortic and
      pulmonary vasculature.
AB  - OBJECTIVE: To compare the enhancement of the pulmonary and aortic vasculature
      between a biphasic injection 64-slice, a single-phase injection 16-slice, and a
      single-phase injection 10-slice multidetector computed tomographic (CT)
      angiography (CTA) protocols. METHODS: With institutional review board approval
      and Health Insurance Portability and Accountability Act compliance, 50 patients
      (16 men, 34 women; mean age, 51.5 years; range, 30-75 years) with atypical chest
      pain from the emergency department were scanned using a triple rule-out protocol
      on a 64-slice CT scanner. Pulmonary enhancement was compared with 50 patients (21
      men, 29 women; mean age, 65.6 years; range, 38-90 years) imaged with a single
      phase 16-slice pulmonary angiography protocol. Aortic enhancement was compared
      with 24 patients (12 men, 12 women; mean age, 66.1; range, 34-92 years) who were
      imaged with a 16-slice aortic dissection CTA protocol and to 25 patients (15 men,
      10 women; mean age, 50.8 years; range, 20-83 years) imaged with a 10-slice aortic
      dissection CTA protocol. A 2-tailed Student t test or sign test was used to
      assess significant differences from a vascular attenuation cutoff value of 250
      Hounsfield units (HU). RESULTS: Individual mean pulmonary arterial and aortic
      attenuation values were statistically significantly less than 250 HU for the 16-
      and 10-slice protocols and statistically significantly more than 250 HU for the
      64-slice protocols (P < 0.05). Mean pooled pulmonary attenuation values were more
      than 250 HU in 18% (9/50) of the 16-slice and in 93% (39/42) of the 64-slice
      protocols. Mean pooled aortic attenuation values were more than 250 HU in 18.4%
      (9/49) of the 10- and 16- and in 100% (42/42) of the 64-slice protocols.
      CONCLUSIONS: The triple rule-out 64-slice biphasic injection breath hold CTA
      protocol provides significantly higher attenuation of aortic and pulmonary
      vasculature compared with our current 10- and 16-slice protocols.

PMID- 18043358
TI  - Diagnosis of metastatic melanoma to the heart with an intrinsic contrast approach
      using melanin inversion recovery imaging.
AB  - Melanoma not infrequently metastasizes to the heart where it either remains
      occult or produces a very variable clinical picture. Recognition of metastatic
      lesions can be difficult on echocardiography because they are frequently
      intramural rather than intracavity. Magnetic resonance imaging with gadolinium
      contrast enhancement has previously been reported as the optimum method for
      identification of cardiac melanoma. This article presents an alternative approach
      that exploits the intrinsic paramagnetic properties of melanin to provide
      inherent contrast without the need for intravenous gadolinium injection. This
      approach is reported here in 3 patients with cardiac melanoma, and its accuracy
      is compared with a traditional gadolinium-enhanced method. We demonstrated that
      there were no significant differences among number, location, and volume of
      detected lesions using an inversion recovery sequence with or without intravenous
      gadolinium contrast.

PMID- 18043359
TI  - Computed tomography features of acute thrombosis of central veins with perivenous
      inflammatory changes.
AB  - OBJECTIVE: Our purpose was to examine the computed tomographic findings in 13
      patients with acute deep venous thrombosis (DVT) of central veins of the neck,
      chest, and abdomen in whom major perivenous inflammatory changes were noted.
      METHODS: During a 10-year period, 13 patients with acute DVT of 21 central veins
      and marked perivenous inflammatory changes on computed tomography were
      identified. Computed tomography images were assessed for location of DVT and
      pattern of perivenous changes. RESULTS: The perivenous changes took the form of a
      rounded or lobulated perivenous bulky mass (massive pattern or tumorlike) in 5
      patients and of infiltrative changes in the other 8 patients. Direct
      visualization of the thrombotic vein was possible in 8 patients. Follow-up
      examinations (range, 6-36 months; mean, 15 months) demonstrated resolution of
      perivenous inflammatory changes with anticoagulation therapy in all cases.
      CONCLUSION: Perivenous inflammatory changes around the thrombotic vein presented
      as a rounded or lobulated perivenous bulky mass that may mimic a tumor or as
      infiltrative perivenous changes.

PMID- 18043360
TI  - Volume histogram analysis for lung thin-section computed tomography:
      differentiation between usual interstitial pneumonia and nonspecific interstitial
      pneumonia.
AB  - OBJECTIVE: The aim of this study was to evaluate volume histogram analysis
      between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia
      (NSIP). METHODS: Sixty cases (UIP, n = 22; NSIP, n = 38) were evaluated
      retrospectively. Three parameters (contrast, variance, and entropy) were
      calculated in 3 types of regions of interest (ROIs): (a) whole lung, (b) right
      lower lobe, and (c) cubic ROIs. To evaluate the influence of extent of abnormal
      findings, the numbers of voxels with low or high density in whole lung were
      compared with the 3 parameters. RESULT: No significant differences were observed
      between the ROIs of whole lung and the right lower lobe. In all cubic ROIs,
      entropy in UIP was larger than that in NSIP (P < 0.001). The numbers of voxels
      with low-density areas significantly correlated with the values of contrast and
      entropy, whereas those with high-density areas significantly correlated with all
      3 parameters. CONCLUSION: Volume histogram analysis for cubic ROIs may be
      feasible for differentiating between UIP and NSIP.

PMID- 18043361
TI  - Pulmonary cavitary nodules on computed tomography: differentiation of malignancy
      and benignancy.
AB  - OBJECTIVE: To establish computed tomographic findings that enable accurate
      differentiation between malignant and benign cavitary lung nodules. METHODS:
      Computed tomographic scans from 39 patients with malignant cavitary nodules and
      from 39 patients with benign cavitary nodules were independently assessed by 2
      observers. They recorded the computed tomographic findings of both types of
      cavitary nodules and surrounding pulmonary parenchyma. The computed tomographic
      findings were then compared using chi test. RESULTS: The notch was found in 29%
      of benign cavitary nodule cases and in 54% of malignant cavitary nodule cases (P
      < 0.01). An irregular internal wall was found in 26% of benign nodules and in 49%
      of malignant nodule cases (P < 0.01). A linear margin (P < 0.01), satellite
      nodule presence (P < 0.01), bronchial wall thickening (P < 0.05), consolidation
      (P < 0.05), and ground-glass attenuation (P < 0.01) were significantly more
      frequent in benign cavitary nodules than in malignant ones. CONCLUSIONS: Although
      the computed tomographic findings of benign and malignant cavitary nodules
      overlap, some computed tomographic findings are useful for differentiating
      cavitary nodules.

PMID- 18043363
TI  - Evaluation of pulmonary lobe variations using multidetector row computed
      tomography.
AB  - PURPOSE: To examine incomplete pulmonary lobes and their variations using
      multiplanar reformation (MPR) techniques of isotropic voxel data produced by
      multidetector row computed tomography (CT). MATERIALS AND METHODS: The subjects
      were 1000 patients who underwent thoracic CT. All examinations were performed
      using 16-row multidetector CT with a slice thickness of 1 mm. Interlobar fissures
      were observed by scrolling MPR techniques for various directions. RESULTS:
      Incomplete interlobar fissure was observed in 42.2% of subjects. Incomplete
      interlobar fissures between the right upper and middle lobes were observed in
      20.4% of subjects, right major fissure was recorded in 17.4%, and left major
      fissure in 19.2%. Excessive fissure formation was observed in 8% of subjects (4
      lobes on the right in 5.7%, 3 lobes on the left in 2.3%). Approximately half of
      the subjects with incomplete interlobar fissures had coexisting abnormalities in
      other lobes, whereas approximately one third of those with excessive fissures had
      coexisting abnormalities in other lobes. CONCLUSIONS: The incidence of incomplete
      lobulation observed by multidetector CT in this study is remarkably lower than
      that reported in previous CT studies but is comparable with that reported from
      autopsy results. It is important to perform multidirectional observation using
      MPR.

PMID- 18043362
TI  - Chest computed tomographic findings and clinical features of legionella
      pneumonia.
AB  - OBJECTIVE: To describe the chest radiographic and computed tomographic (CT)
      findings of legionella pneumonia. METHODS: Serial chest radiographs and CT scans
      obtained in 12 patients with serologically proven Legionella pneumophila
      pneumonia were retrospectively reviewed. Chest CT findings were analyzed with
      regard to patterns and distributions of pulmonary abnormalities. RESULTS: Nine of
      the 12 patients were in an immunocompromised state, that is, steroid therapy (n =
      8) and myelodysplastic syndrome (n = 1), and 6 of the 8 steroid users were on
      high-dose steroid. All patients showed multilobar or multisegmental pulmonary
      infiltrates on CT scans. The CT findings were categorizable as; predominantly
      airspace consolidations (n = 6), mixed lesions with lobular consolidation and
      ground-glass opacity (GGO) (n = 3), and pure GGO lesions (n = 2). Five of the 6
      patients on high-dose steroid therapy had lobar consolidations with (n = 4) or
      without a cavity (n = 1), and 1 patient had a mixed lesion. CONCLUSIONS: The most
      common CT findings in legionella pneumonia were multilobar or multisegmental
      consolidation and GGO. Cavitary lobar consolidation occurred commonly in patients
      on high-dose steroid therapy.

PMID- 18043364
TI  - CT of the foot: selected inflammatory arthridites.
AB  - Although the primary imaging modality for the evaluation of inflammatory
      arthritis of the foot and ankle is currently magnetic resonance imaging, computed
      tomography may be performed in some patients and can aid in diagnosis. This
      article reviews a number of inflammatory arthritic conditions that involve the
      feet. Computed tomographic findings and the role of computed tomography in
      diagnosing infection, gout, and rheumatoid arthritis of the foot are discussed.

PMID- 18043365
TI  - Magnetic resonance imaging of the rotator interval in patients on long-term
      hemodialysis: correlation with the range of shoulder motions.
AB  - OBJECTIVE: To assess the rotator interval of patients on long-term hemodialysis
      with magnetic resonance imaging (MRI) for the presence of adhesive capsulitis and
      to correlate these findings with shoulder motions. METHODS: Seventeen shoulders
      in 16 patients (mean age, 53.8 years) on hemodialysis (range of duration, 4-28
      years) who had pain and limited range of shoulder motion underwent MRI. Rotator
      interval was inspected in 3 regions (subcoracoid area, above the subscapularis
      muscle, and around the biceps tendon) on sagittal magnetic resonance images with
      regard to increased nonfatty soft tissue intensity as none, mild, moderate, and
      marked. Magnetic resonance images were evaluated by 2 musculoskeletal
      radiologists with consensus. Ranges of motion for external and internal rotation
      and abduction and forward flexion were assessed either normal or mildly,
      moderately, and severely limited. RESULTS: Increased nonfatty soft tissue
      intensity within the rotator interval fat was observed in 11 shoulders (65%).
      Very strong positive correlation was found between the limitation of external
      rotation and the presence of nonfatty soft tissue infiltrating all 3 areas of the
      rotator interval fat (rs, between 0.81 and 0.96; P < 0.001). Strong positive
      correlation was found between the hemodialysis duration and the presence of
      nonfatty soft tissue infiltrating all 3 areas of the rotator interval fat (rs,
      between 0.68 and 0.71; P <or= 0.002). CONCLUSIONS: Long-term hemodialysis results
      in adhesive capsulitis-like MRI findings in the shoulder joint with nonfatty soft
      tissue infiltration in the rotator interval that is related to hemodialysis
      duration. The degree of MRI obliteration of the rotator interval fat strongly
      correlates with the range limitation of some shoulder motions.

PMID- 18043366
TI  - Digital tomosynthesis aided by low-resolution exact computed tomography.
AB  - Tomosynthesis reconstructs 3-dimensional images of an object from a significantly
      fewer number of projections as compared with that required by computed tomography
      (CT). A major problem with tomosynthesis is image artifacts associated with the
      data incompleteness. In this article, we propose a hybrid tomosynthesis approach
      to achieve higher image quality as compared with competing methods. In this
      approach, a low-resolution CT scan is followed by a high-resolution tomosynthesis
      scan. Then, both scans are combined to reconstruct images. To evaluate the image
      quality of the proposed method, we design a new breast phantom for numerical
      simulation and physical experiments. The results show that images obtained by our
      approach are clearly better than those obtained without such a CT scan.

PMID- 18043367
TI  - A method for calibrating diffusion gradients in diffusion tensor imaging.
AB  - OBJECTIVE: To calibrate and correct the gradient errors including gradient
      amplitude scaling errors, background/imaging gradients, and residual gradients in
      diffusion tensor imaging (DTI). METHODS: A calibration protocol using an
      isotropic phantom was proposed. Gradient errors were estimated by using linear
      regression analyses on quadratic functions of diffusion gradients along 3
      orthogonal directions. A 6-element total effective scaling vector is generated
      from the calibration protocol to retrospectively correct gradient errors in DTI
      experiments. RESULTS: The accuracy of the calibration protocol was within 1% or
      less in estimating gradient scaling errors. On both the brain study and the
      computer simulations, the retrospective correction minimized undesirable estimate
      biases of DTI measurements due to gradient errors. CONCLUSION: The protocol and
      retrospective correction are shown to be effective. The method may be used for
      prospective correction if actual diffusion-gradient waveforms are available. The
      methodology is expandable to general diffusion imaging schemes.

PMID- 18043368
TI  - Hepatoid adenocarcinoma: computed tomographic imaging findings with
      histopathologic correlation in 6 cases.
AB  - OBJECTIVE: Hepatoid adenocarcinoma (HAC) is a special type of primary tumor with
      aberrant hepatocellular differentiation occurring in extrahepatic organs. Our
      objective was to review the computed tomographic findings of HAC and to correlate
      the imaging features with histopathologic findings. Institutional review board
      approval was obtained for this study. METHODS: The computed tomographic findings
      images in 6 consecutive patients with pathologically proven HAC were reviewed
      retrospectively. Five patients were men and 1 was a woman (mean age, 56 years;
      age range, 36-68 years). All patients underwent contrast-enhanced computed
      tomography (CT) performed on a 4-slice multidetector row CT scanner. The mean
      time interval between CT and surgery was 5 days. Two radiologists who were
      unaware of the final histological diagnosis reviewed all computed tomographic
      images retrospectively. Lesion characteristic (ie, number, location, size,
      density, enhancement, heterogeneity, margin, distribution, presence of necrosis,
      lymphadenopathy, and distant metastasis) were evaluated. The correlation between
      the imaging and the pathological findings was analyzed. RESULTS: Most patients
      had elevated serum alpha-fetoprotein levels (n = 4). The HAC appeared as large
      tumors (mean size, 4.2 x 3.4 x 3.9 cm), isodense at unenhanced CT (n = 4),
      moderately enhanced (n= 5), with necrotic areas (n = 6), regional lymphadenopathy
      (n = 5), and distant metastases (n = 4). The heterogeneity on computed
      tomographic images correlated well with the presence of hemorrhage and necrosis.
      CONCLUSIONS: In an old patient with a large necrotic and moderately vascular
      tumor, the presence of distant metastases, regional lymphadenopathy, and
      characteristic increased serum alpha-fetoprotein level may suggest a diagnosis of
      HAC.

PMID- 18043369
TI  - Management of open fractures in pediatric patients: current teaching in
      Accreditation Council for Graduate Medical Education (ACGME) accredited residency
      programs.
AB  - The purpose of this study was to determine the method of treatment for open
      fractures in pediatric patients that is used and taught at academic orthopedic
      residency programs. A web-based survey was constructed and emailed to program
      directors of orthopedic residencies. Seventy programs out of a total of 140
      surveyed programs responded. Data were tabulated and charts created in an Excel
      spreadsheet. Type I fractures were treated by most with a cephalosporin alone
      (97%) for less than 48 h (87%). Type II were treated by most programs with a
      cephalosporin alone with no aminoglycoside (84%) for less than 48 h (80%). Type
      IIIa were treated by most programs with a cephalosporin and an aminoglycoside
      (50%) for less than 48 h (60%). Type IIIb were treated by most programs with a
      cephalosporin and aminoglycoside (54%) for less than 48 h (53%). Type IIIc were
      also treated by most with a cephalosporin and an aminoglycoside (53%) for less
      than 48 h (51%). Wounds were closed by most responders for type I (90%), type II
      (86%) and type IIIa (50%) but not type IIIb (10%), and type IIIc (16%). For the
      programs responding to the pediatric section of the survey over half (53%)
      reported using a trauma room and 58% reported allowing residents to irrigate and
      debride wounds in the emergency room. In conclusion, for pediatric patients most
      orthopedic residencies use a cephalosporin alone for type I and type II open
      fractures with an aminoglycoside added for type III fractures. Treatment is
      typically for 48 h or less. Delay of 6 h seems to be accepted for type I and type
      II fractures but not type III fractures.

PMID- 18043370
TI  - Treatment of complicated pediatric femoral fractures with titanium elastic nail.
AB  - Nonunion and major complications are not very common in pediatric fractures. No
      commonly accepted methods exist for the treatment of these fractures. In this
      study, treatment of complicated pediatric femoral fractures with titanium elastic
      nails was evaluated. Five girls and four boys with nine femoral fractures
      constituted the group. The mean age of the patients was 8.7 (5-11) years and the
      mean follow-up was 46.6 (24-84) months. Five of them had implant failure and
      nonunion, two of them had loss of position in the external fixator, one of them
      had incomplete union and loss of position in the external fixator and the other
      had femoral fracture in the lengthening segment of the femur and had loss of
      position and incomplete union in the spica cast. All the patients were treated
      with a closed or open reduction of the fracture, debridement if treated with open
      method and fixation of the fracture with titanium elastic nails. Complete union
      was achieved in all the patients within the 6-9 months. No neurovascular injury
      or infection was reported in the group. The result of the treatment showed that
      fixation of complicated pediatric femoral fractures with intramedullary titanium
      elastic nails is a good option.

PMID- 18043371
TI  - Calcaneal apophyseal fractures in young athletes: two case reports.
AB  - Calcaneal apophyseal fracture is especially rare in young children. Furthermore,
      this type of fracture is sometimes overlooked in children because of subtle
      radiographic findings. The studies reported on this fracture are rare. We report
      two calcaneal apophyseal fractures that were present in the proximal half of
      calcaneal apophysis and were treated with fixation of the avulsed bony fragment
      using nonabsorbable suture.

PMID- 18043372
TI  - Ulnar styloid fracture in children: a retrospective study of 46 cases.
AB  - Ulnar styloid fractures are frequently ignored in the treatment of wrist
      fractures in children. Forty-six untreated ulnar styloid fractures (40 tip and
      six base fractures) associated with radial injuries (45 patients) were
      retrospectively analysed. At the removal of the cast, we recorded that 80% had a
      nonunion of the styloid fracture. Thirty-five patients were reviewed at an
      average of 19 months after treatment. Thirty tip fractures and five base
      avulsions were found. We recorded 28 patients with a good clinical result despite
      21 cases of nonunion, whereas seven patients (all nonunions) had a fair result.
      All the fair results suffered from intermittent pain during sports and movement,
      radioulnar joint instability and tears of the triangular fibrocartilage complex.
      It can be concluded that both distal radius and ulnar styloid fractures should be
      taken into account in the initial treatment and pain associated with a nonunion
      of the ulnar styloid in a child may be due to a tear of the triangular
      fibrocartilage complex.

PMID- 18043373
TI  - Bilateral valgus-extension osteotomy of hip using hybrid external fixator in
      spondyloepiphyseal dysplasia: early results of a salvage procedure.
AB  - The treatment of spondyloepiphyseal dysplasia (SED) congenita patients with
      severe bilateral hip involvement is difficult because it involves deformities of
      multiple joints and of the spine. The purpose of this study was to evaluate the
      results of the procedure described below as a method of treatment for bilateral
      hip involvement in SED congenita patients. We performed proximal femoral valgus
      extension osteotomy with distal femoral varus osteotomy using a hybrid external
      fixator in eight patients (seven male patients and one female patient) or 16
      hips. The patients had a mean age of 16.37 years (range, 9-25 years) at the time
      of surgery. The mean valgus angle at the proximal osteotomy site was 53.4 degrees
      on the right side and 52.5 degrees on the left side, and the mean varus angle at
      the distal osteotomy site was 22 degrees . Mean fixator time was 19.8 weeks
      (range, 10-42 weeks). After an average follow-up of 25.9 months, the mean
      modified Harris hip score had improved from 67.9 points to 79.1 points, which was
      statistically significant (P=0.012). Preoperative knee range of motion was
      achieved at the last follow-up in all patients. Waddling gait was absent in three
      patients, reduced in four patients, and was the same in one at the last follow
      up. Mean limb length gain was 3.5 cm (range, 0-5 cm), mean limb length
      discrepancy less than 0.5 cm, and the mechanical axis was realigned in all. In
      conclusion, our early results suggest that proximal valgus-extension osteotomy
      with distal femoral varusization can be a useful treatment option in young
      patients with bilateral hip involvement in SED congenita.

PMID- 18043374
TI  - Proximal femoral resection and articulated hip distraction with an external
      fixator for the treatment of painful spastic hip dislocations in pediatric
      patients with spastic quadriplegia.
AB  - We describe the results obtained with an alternative method of treatment for
      spastic painful hip dislocations in nonambulatory patients, which consists of a
      proximal femoral resection with capsular interposition arthroplasty, and the
      addition of a hinged external fixator for postoperative articulated hip
      distraction to allow for an immediate upright position and the ability to sit in
      a wheelchair. We performed this technique in three patients (four hips) with a
      mean age at the time of surgery of 15 years. Postoperatively, clinical
      improvement was observed in all four hips, with respect to pain relief, sitting
      tolerance, perineal care and functional range of motion.

PMID- 18043375
TI  - Posterior vertebrectomy in kyphosis, scoliosis and kyphoscoliosis due to
      hemivertebra.
AB  - Vertebrectomy and instrumentation only via the posterior approach has been
      increasingly used in sagittal, frontal plane and combined deformities. The aim of
      this retrospective study is to evaluate the clinical and radiological results of
      hemivertebrectomy and instrumentation only via the posterior approach in
      congenital spinal deformities. Between 1998 and 2003, we performed
      hemivertebrectomy and interbody fusion using posterior instrumentation with
      titanium mesh cage via the posterior approach in 19 patients (three scoliosis,
      five kyphosis and 11 kyphoscoliosis). The age of the patients ranged from 2 to 22
      years and they all underwent hemivertebrectomy (at thoracic level in six
      patients, at thoracolumbar level in eight patients and at lumbar level in five
      patients). A titanium mesh cage was used for anterior column support and
      interbody fusion in patients who had residual anterior gap preventing bone-to
      bone contact. Correction and stabilization were achieved by posterior polyaxial
      pedicle screws. Follow-up was an average of 4.6 years (range: 2-7 years). We did
      not confront any loss of correction, pseudoarthrosis, and titanium mesh cage
      collapse or implant failure. Hemivertebrectomy and instrumentation via the
      posterior approach is a good one-stage surgical treatment option that can be used
      to avoid the surgical trauma and morbidity related to anterior surgery. It is a
      technically demanding surgical procedure, however, requiring extreme care and
      experience in spine surgery.

PMID- 18043376
TI  - Discitis and isthmic spondylolisthesis: a case report.
AB  - Spondylolysis and spondylolisthesis are common causes of low back pain in
      children and adolescents. Disc space infection is less common, but is another
      cause of severe back pain in this population. The combination of both processes
      in the same segment is rare. This case report is of a 13-year-old patient with
      isthmic lumbosacral spondylolisthesis and disc space infection at the same level.
      A patient who presented with severe low back pain and a radiological picture of
      isthmic slip with end plate irregularities and anterior bridging osteophyte was
      diagnosed with disc space infection at the slip level. He was managed with
      intravenous antibiotics for 6 weeks, followed by oral medication for an
      additional 2 weeks. At follow-up 28 weeks later, a spontaneous radiological
      fusion at the slip level was noted with complete relief of his symptoms. The
      patient was able to resume sports activities. In conclusion, isthmic
      spondylolisthesis and disc space height infection might coexist. Nonoperative
      treatment will usually result in spontaneous fusion and the complete relief of
      symptoms.

PMID- 18043377
TI  - The correction of leg-length discrepancy after treatment in developmental
      dysplasia of the hip by using a percutaneous epiphysiodesis.
AB  - The aims of this study were to determine factors that cause a leg-length
      discrepancy (LLD) to the extent that correction is indicated after treatment in
      developmental dysplasia of the hip and determine whether the LLD may be treated
      with a percutaneous epiphysiodesis. Twelve children were included in this study.
      The factors which caused LLD were avascular necrosis, femoral shortening and
      varus at reduction, and septic arthritis. Percutaneous epiphysiodesis of the
      contralateral limb reduced the mean predicted LLD from 3.8 to 1.2 cm at maturity.
      We concluded that LLD (>2.5 cm) might result from complications of developmental
      dysplasia of the hip and these patients can be treated with a percutaneous
      epiphysiodesis.

PMID- 18043378
TI  - Patellar dislocation in achondroplasia.
AB  - The knee was assessed by normal plain radiographs in 20 achondroplasia patients
      (40 lower extremities), whose age ranged from 10.5 to 23 years. Five patients
      (seven knees) had permanent patellar dislocation. There was a significant
      difference between the achondroplasia group and control group (50 knees without
      skeletal dysplasia) for femoral sulcus angle but not for femorotibial angle,
      Insall-Salvati index and Q angle. Patellar dislocation for achondroplasia may be
      caused not only by the abnormalities of soft tissue but also a small groove of
      patellofemoral joint as a bony malformation.

PMID- 18043379
TI  - Correspondence: nailing of children's diaphyseal fractures using stainless steel
      Kirschner wires.

PMID- 18043382
TI  - Correspondence: late presenting dislocation of sonographically stable hips.

PMID- 18043383
TI  - Correspondence: treatment of severe late onset Perthes disease with soft tissue
      release and articulated hip distraction (Reply).

PMID- 18043384
TI  - Computer-assisted detection for pulmonary embolism on MDCT: can CAD help Rad?

PMID- 18043385
TI  - Pulmonary embolism: computer-aided detection at multidetector row spiral computed
      tomography.
AB  - BACKGROUND: We aimed to evaluate the feasibility and performance of a computer
      aided detection (CAD) tool for automated detection of segmental and subsegmental
      pulmonary emboli. METHODS: A CAD tool (ImageChecker CT, R2 Technology, Inc) for
      automated detection of pulmonary emboli was evaluated on multidetector-row CT
      studies of varying diagnostic quality in 23 patients (13 female, mean age 52 y)
      with pulmonary embolism (PE) and of 13 patients (all female, mean age 49 y)
      without PE. A collimation of 16 x 1 mm and a reconstructed section width of 1.25
      mm had been used in each patient. The performance of the CAD tool for the
      detection of emboli in the segmental and subsegmental pulmonary arterial tree was
      assessed. Consensus reading of the same studies by 2 radiologists, with a third
      for adjudication, for the identification of segmental and subsegmental pulmonary
      emboli was used as the standard of reference. RESULTS: Consensus reading revealed
      130 segmental pulmonary emboli and 107 subsegmental pulmonary emboli in the 23
      patients with PE. All 23 patients with PE were correctly identified as having PE
      by the CAD system. In a vessel-by-vessel analysis, the sensitivity of the CAD
      algorithm was 92% (119/130) for the detection of segmental pulmonary emboli and
      90% (92/107) for subsegmental pulmonary emboli. The overall specificity, positive
      predictive value (95% confidence interval) and negative predictive value (95%
      confidence interval) of the algorithm were 89.9%, 63.2% (57.9%-68.2%) and 97.7%
      (96.7%-98.4%), respectively. The average false positive rate of the CAD algorithm
      was 4.8 (range 1 to 9) false positive detection marks per case. CONCLUSION: CAD
      of segmental and subsegmental pulmonary emboli based on 1-mm multidetector-row CT
      studies is feasible. Application of CAD tools may improve the diagnostic accuracy
      and decrease the interpretation time of computed tomographic angiography for the
      detection of pulmonary emboli in the peripheral arterial tree and further enhance
      the acceptance of this test as the first line diagnostic modality for suspected
      PE.

PMID- 18043386
TI  - Computer-aided detection of pulmonary embolism on CT angiography: initial
      experience.
AB  - OBJECTIVE: To evaluate the performance of a computer-aided detection (CAD) system
      for diagnosis of pulmonary embolism on computed tomography (CT) pulmonary
      angiography. MATERIALS AND METHODS: One hundred and four pulmonary CT angiograms
      for pulmonary emboli (PE) were reviewed both by radiologists and a CAD detection
      system (ImageChecker CT V2.0, R2 Technology Inc, Sunnyvale, CA). CT scans, read
      and reported by radiologists in a routine daily clinical setting, were later
      processed by the CAD system. The performance of the CAD system was analyzed.
      RESULTS: Forty-five PE were identified by the radiologists in 15 patients. The
      CAD system revealed 123 findings, interpreted by the system as PE. Twenty-six of
      them, detected in 8 patients, represented true-positive results. Ninety-seven
      (78.9%) CAD findings were not true PE and were defined as false-positive.
      Nineteen true PE in 7 patients were missed by the CAD system constituting 42%
      false-negative rate. Sensitivity of the CAD system was 53.3% and the specificity
      was 77.5%. The positive predictive value of CAD system was 28.5% and the negative
      predictive value was 90.7%. CONCLUSIONS: With the evaluated CAD system, it is
      relatively simple and fast to check all detected findings and decide if they
      represent true PE. However, high false-negative results demand technologic
      improvement, to increase the sensitivity of the system. It is anticipated to
      become a promising supplement to the work and eyes of the radiologist in
      detecting PE on pulmonary CT angiography.

PMID- 18043387
TI  - Prevalence and significance of incidental extracardiac findings at 64
      multidetector coronary CTA.
AB  - INTRODUCTION: Computed tomography (CT) angiography of the coronaries has the
      ability to depict extracardiac lesions in the visualized thorax and upper
      abdomen. These incidental lesions can often present a challenge to physicians.
      METHODS: We performed a retrospective review of 100 consecutive patients referred
      for 64-multidetector CT coronary CT angiography performed on a 64-slice CT
      scanner. Two fellowship trained cardiac radiologists reviewed each study by
      consensus on a CT postprocessing workstation using commercially available
      software. Extracardiac CT findings (ECF) were classified as benign,
      indeterminate, or of clinical significance at the time of image evaluation.
      Benign findings were those considered to be of little clinical significance with
      no follow-up needed. Indeterminate findings were those deemed of potential
      clinical importance, requiring correlation of the patient history or a follow-up
      study. Clinically significant findings were those felt to be of definite clinical
      importance requiring immediate evaluation or intervention. RESULTS: The study
      cohort consisted of 68 males (68%) and 32 females (32%) with a mean (+/-standard
      deviation) age of 63.4+/-14.5 years and a range of 23 to 87 years. A total of 145
      ECF were found in 67 patients (67%), 50 males and 17 females, with a mean age of
      68.0+/-11.8 years and a range of 23 to 87 years. Of those, 107 (73.8%) were
      considered benign, 22 (15.2%) indeterminate, and 16 clinically significant
      findings (11.0%). By significance, a total of 107 benign ECF were found in 61
      patients, 46 males and 15 females, with a mean age of 67.7+/-12.2 years and a
      range of 23 to 87 years. Only 22 ECF indeterminate findings were present,
      distributed in 21 patients, of which there were 17 males and 5 females, with a
      mean age of 68.5+/-13.9 and a range of 23 to 82 years. The 16 clinically
      significant ECF were distributed in 11 patients, all males, with a mean age of
      68.0+/-8.8 and a range of 55 to 87 years. CONCLUSIONS: The presence of ECF in our
      daily practice is frequent, and not limited to the identification of pulmonary
      nodules, and reinforces the notion that all the organs in the scan should be
      thoroughly and methodically evaluated.

PMID- 18043388
TI  - Air-leak syndromes in hematopoietic stem cell transplant recipients with chronic
      GVHD: high-resolution CT findings.
AB  - OBJECTIVES: The purpose of this study was to determine the incidence and the high
      resolution computed tomography findings of air-leak syndromes in a large group of
      hematopoietic stem cell (HSC) transplant recipients with proved chronic graft
      versus host disease (cGVHD). MATERIALS AND METHODS: High-resolution computed
      tomography scans of 9 allogeneic HSC transplant recipients (8 men, 1 woman; 19 to
      45 years of age; median 28 y), with a proven diagnosis of cGVHD-related
      bronchiolitis obliterans syndrome (BOS) were reviewed for the presence,
      appearance, and distribution of abnormalities. RESULTS: Nine patients with cGVHD
      developed 10 episodes of spontaneous air-leak syndromes secondary to cGVHD
      related BOS during the study period analyzed; for a 2-year estimated cumulative
      incidence of 2.1% (95% confidence interval 0.2% to 3.8%) its prevalence was 5.7%
      (95%CI: 2.6% to 10.5%). All cases were allogeneic HSC transplant recipients with
      cGVHD who acquired new respiratory symptoms and/or radiologic abnormalities.
      Pneumomediastinum and pneumothorax were present in 6 patients. Subcutaneous
      emphysema was identified in 3 patients and pulmonary interstitial emphysema in 2
      patients. A combination of different air-leak syndromes was observed in 6
      patients. CONCLUSION: Air-leak syndromes represent an uncommon late complication
      in HSC transplant recipients with cGVHD-related BOS.

PMID- 18043389
TI  - A variant of Poland syndrome associated with dextroposition.
AB  - Poland syndrome is characterized by partial or complete absence of pectoralis
      muscles, ipsilateral syndactyly, and occasionally other malformations of the
      anterior chest wall and breast. Other associated anomalies, including
      dextrocardia, renal malformations, and vertebral anomalies, have been reported in
      rare cases. The condition is more frequent among males, and usually occurs on the
      right hemithorax in the unilateral form. The syndrome is believed to be caused by
      a genetic disorder that reduces the embryonal circulation in the subclavian and
      vertebral arteries. We report a 20-year-old man with Poland syndrome on the left
      hemithorax, which is rarely associated with dextroposition.

PMID- 18043390
TI  - Diffuse left ventricular myocardial calcification in the setting of sepsis on CT
      imaging.
AB  - We describe a 58-year-old man with acute lymphoblastic leukemia who developed
      diffuse left ventricular myocardial calcification during an episode of sepsis
      seen at computed tomographic imaging.

PMID- 18043391
TI  - MDCT and 3D evaluation of type 2 hypoplastic pulmonary artery sling associated
      with right lung agenesis, hypoplastic aortic arch, and long segment tracheal
      stenosis.
AB  - The early diagnosis and complete anatomic evaluation of pulmonary artery sling, a
      congenital vascular anomaly in which left pulmonary artery arises from the right
      pulmonary artery, is paramount for proper patient management, because patients
      with this disorder frequently have other congenital anomalies resulting in high
      morbidity and mortality. Until recently, pulmonary artery sling in the neonate
      has been established with standard radiologic imaging studies such as plain
      radiographs, barium swallow studies, fluoroscopy-guided airway studies, and
      echocardiograms. However, with the development and widespread availability of
      multidetector computed tomography, pulmonary artery sling is increasingly
      evaluated with this newer technology. This case report presents a rare incidence
      of type 2 hypoplastic pulmonary artery sling in a neonate associated with right
      lung agenesis, hypoplastic aortic arch, and long segment tracheal stenosis.
      Multidetector computed tomography combined with 3-dimensional evaluation was
      particularly helpful in making a correct diagnosis of the complicated anatomic
      anomalies found in this case.

PMID- 18043392
TI  - Hypogenetic lung syndrome with anomalous venous return to the left inferior
      pulmonary vein: multidetector row CT findings.
AB  - A unique case of hypogenetic lung syndrome is demonstrated with contrast-enhanced
      multidetector row computed tomography images. This is the first report of
      hypogenetic lung syndrome with anomalous venous return to the left inferior
      pulmonary vein.

PMID- 18043393
TI  - Spindle cell lipoma of the mediastinum: a differential consideration for
      liposarcoma.
AB  - Spindle cell lipoma is a benign lesion most commonly found on the posterior neck
      and shoulders. It shares many imaging characteristics with liposarcoma, including
      the presence of adipose and soft tissue elements. Although its benign nature
      precludes the necessity of surgical resection for treatment, surgery is often
      required for tissue diagnosis. We report a case of spindle cell lipoma arising in
      the anterior mediastinum.

PMID- 18043394
TI  - Pulmonary hemorrhage resulting from bungee jumping.
AB  - Pulmonary hemorrhage is a relatively common complication of blunt chest trauma.
      Occasionally, it may result from pulmonary barotrauma after scuba diving or from
      sports activities not associated with barotrauma such as long breath-hold diving.
      We report a case of symmetric diffuse upper lobe hemorrhage resulting from a
      bungee jump in a previously healthy man. Bungee jumping is an increasingly
      popular sport with relatively few reported injuries. To our knowledge pulmonary
      hemorrhage in this setting has not yet been described.

PMID- 18043395
TI  - IgG4-positive pulmonary disease.
AB  - We report herein high-resolution computed tomography findings from a patient with
      IgG4-related pulmonary disease for the first time. The 61-year-old male patient
      complained of low-grade fever, dry mouth, and night sweats. He was diagnosed as
      having autoimmune pancreatitis, Sjogren syndrome, and elevated serum IgG4. High
      resolution computed tomography of the lungs showed dense alveolar consolidation
      and air bronchograms in bilateral perihilar regions. IgG4-positive
      lymphoplasmacytes were detected in pulmonary lesions by immunostaining of biopsy
      samples. IgG4-related pulmonary disease can be associated with various radiologic
      findings.

PMID- 18043396
TI  - Posterior mediastinal angioleiomyoma: report of a case.
AB  - We describe a case of mediastinal angioleiomyoma in an asymptomatic 72-year-old
      man, who was admitted to our hospital for a mediastinal tumor discovered during
      an annual medical examination. The tumor was evaluated by computed tomography
      (CT) and magnetic resonance imaging (MRI). Unenhanced CT scans demonstrated a
      tumor that was adjacent to the descending aorta. The tumor was partially enhanced
      in the early phase of contrast-enhanced CT, and in the late phase there was
      additional tumor enhancement. With MRI, the tumor displayed a homogeneous low
      signal intensity on the T1-weighted image and a homogeneous very high signal
      intensity on the T2-weighted image. Contrast-enhanced MRI demonstrated the same
      enhancement pattern as CT. The examination results led to a preoperative
      diagnosis of posterior mediastinal hemangioma, and the patient underwent surgery.
      The tumor originated from the supreme intercostal vein, and was diagnosed as an
      angioleiomyoma by histopathologic examination. Because mediastinal
      angioleiomyomas are very rare, they are difficult to diagnose preoperatively.
      However, we believe that CT and MRI can be of significant help in the
      differential diagnosis.

PMID- 18043397
TI  - High-resolution computed tomography findings of diffuse pulmonary involvement by
      mycosis fungoides.
AB  - The authors describe a case of diffuse pulmonary involvement by mycosis fungoides
      in a 55-year-old man who presented with progressive exertional dyspnea. Although
      he had a long history of skin lesions, mycosis fungoides remained undiagnosed at
      initial presentation. High-resolution computed tomography revealed hazy ground
      glass opacities along the thickened bronchovascular bundles and interlobular
      septa, particularly in the mid and upper lung fields, and traction bronchiectasis
      in the central regions. Skin biopsy confirmed the diagnosis of mycosis fungoides
      in the plaque stage. Transbronchial lung biopsy revealed diffuse infiltration of
      the atypical lymphoid cells in the peribronchial and perivascular regions. In
      this case, high-resolution computed tomography played an important role for
      suggesting the lymphoproliferative disease in this patient with undiagnosed
      mycosis fungoides.

PMID- 18043398
TI  - Mediastinal lung herniation associated with pulmonary sequestration.
AB  - Mediastinal lung herniation is a rare condition characterized by protrusion of 1
      lower lung through behind the heart into the opposite side of the chest, usually
      from right to left. We present a case of mediastinal lung herniation associated
      with pulmonary sequestration, which was confirmed both surgically and
      pathologically in a 13-year-old girl initially admitted with a diagnosis of
      pneumonia. Contrast-enhanced computed tomographic images using a multidetector
      row computed tomography clearly demonstrated the right lung herniation toward the
      left and 2 aberrant systemic arteries supplying the sequestered lung mass. These
      arteries run through the herniated lung from right to left. Additionally, on the
      basis of pleural anatomy, we discuss herein the difference between a mediastinal
      lung herniation and horseshoe lung.

PMID- 18043399
TI  - High-resolution CT findings in pulmonary hyalinizing granuloma.
AB  - A 47-year-old man with pulmonary hyalinizing granuloma is herein presented. The
      patient, whose chief complaint was a mild cough, was found by chest radiograph to
      have multiple bilateral nodules. Subsequent high-resolution computed tomography
      demonstrated multiple slightly irregular nodules, perinodular ground-glass
      opacity, peribronchovascular interstitial thickening, and cysts. A mild
      enlargement of systemic lymph nodes was also noted. Laboratory tests disclosed a
      slight elevation in the C-reactive protein, gamma-globulin, interleukin-6, and
      soluble interleukin-2 receptor levels. A histopathologic examination of the
      specimen yielded from a thoracoscopic lung biopsy resulted in a definite
      diagnosis of pulmonary hyalinizing granuloma.

PMID- 18043400
TI  - Notes from the 2006 annual meeting of the Korean Society of Thoracic Radiology.

PMID- 18043401
TI  - Quality healthcare is everyone's right.

PMID- 18043402
TI  - Andropause in the aging male patient.

PMID- 18043403
TI  - Management of intraocular inflammation.

PMID- 18043404
TI  - Reclast approved for osteoporosis treatment in postmenopausal women.

PMID- 18043405
TI  - Alternative dispute resolution: an overview.

PMID- 18043406
TI  - Bleeding disorders: patient history key to diagnosis.

PMID- 18043408
TI  - Life with Lou Gehrig's disease: managing ALS symptoms.

PMID- 18043410
TI  - Radioimmunotherapy in the treatment of non-Hodgkin's lymphoma.

PMID- 18043411
TI  - Informed consent for patients with cognitive impairment.

PMID- 18043419
TI  - Merton C. Flom, OD, PhD--a paradigm of optometric leadership.
AB  - Dr. Merton Flom serves as the quintessential model for demonstrating what it
      takes to be an outstanding scientist, clinician, and educator. Professor Flom's
      career as a clinician, vision scientist, and visionary in optometry is well known
      to most faculty in optometric institutions, but many in the profession may not be
      aware of his enormous contributions. This profile captures Dr. Flom's
      professional and personal views about optometry, vision research, and education.

PMID- 18043420
TI  - Oscillopsia in "inverse latent" infantile nystagmus syndrome.
AB  - PURPOSE: A possibly unique individual with infantile nystagmus syndrome presented
      with incessant oscillopsia but good stereopsis when viewing binocularly; her
      nystagmus was greatly reduced with left eye occlusion. We have attempted to
      explain this and to identify an intervention that preserves binocular vision
      while maximizing perceptual stability. CASE REPORT AND METHODS: Eye movements
      were recorded and analyzed for duration of foveation (% time when the target was
      on or near the fovea and the eye was moving at < or = 4 degrees /sec) under
      different viewing conditions. Changes in foveation were compared with the
      patient's reports of her perceptual stability. RESULTS: In her right gaze null
      with her right eye fixating, foveation was 52.9%. This fell to 32.3% for the same
      eye in primary position and to 0.8% when viewing binocularly in primary position.
      When viewing binocularly oscillopsia was incessant; when viewing with her right
      eye vision was stable except in left gaze. Prism correction of her phoria greatly
      reduced her oscillopsia when viewing binocularly while preserving stereopsis;
      foveation went up to 33.7%. CONCLUSION: The patient's ability to maintain good
      foveation only when viewing with her right eye forces her to choose between
      stereopsis and stable vision. This may result from the rare combination of (1)
      requiring good foveation for oscillopsia suppression and (2) nystagmus
      deteriorating under the stress of maintaining binocularity. There may be many
      other infantile nystagmus syndrome patients who do not develop oscillopsia but
      may suffer sufficient asthenopia from a phoria to exacerbate their nystagmus.

PMID- 18043421
TI  - Depression in older people: visual impairment and subjective ratings of health.
AB  - PURPOSE: The aim of this study was to establish the prevalence of depression in a
      sample of older adults with impaired vision and investigate associations between
      physical and visual disability and depression. METHODS: We analyzed cross
      sectional baseline data from 391 participants aged >or=75 years with visual
      acuity of 6/24 (20/80) or less, recruited for a randomized controlled trial of
      interventions to prevent falls (the VIP trial). Measures included the geriatric
      depression scale (GDS-15), the state-trait anxiety index, activities of daily
      living (Nottingham extended ADL scale), physical activity (human activity
      profile), an index of visual functioning (VF-14), health-related quality of life
      (SF-36), objective measures of physical ability, and a measure of visual acuity.
      Regression models were developed to investigate the association between
      depression scores and physical, psychological, and visual disability. RESULTS:
      About 29.4% (115 of 391) of participants were identified as potentially depressed
      (GDS-15 score >4). Physical function, physical activity, physical ability, visual
      function, anxiety, and self-reported physical and mental health were
      significantly worse for those with depressive symptomatology. Physical, visual,
      and psychological factors collectively explained 41% of the variance in the
      depression score in a linear regression model (R=0.421, adjusted R=0.410, F
      (7,382)=39.680, p<0.001). Depression was not related to age, gender, living
      situation, ethnicity, or number of prescription or antidepressant medications
      taken. CONCLUSIONS: Depression was common in this population of older adults with
      severe visual impairment. Impaired visual and physical functions were associated
      with symptoms of depression. The effect of visual disability was independent of
      the effect of physical disability. The strength of this relationship, and the
      results of the regression analyses, indicate that a person who is visually or
      physically disabled is more likely to suffer from depression.

PMID- 18043422
TI  - Hyperopia and emergent literacy of young children: pilot study.
AB  - PURPOSE: To compare emergent literacy skills in uncorrected hyperopic and
      emmetropic children. METHODS: "Hyperopes" (>or=2.00 D sphere along the most
      hyperopic meridian; n=13; aged 67+/-13 mo) and "emmetropes" (<or=1.50 D sphere
      along the most hyperopic meridian; n=19; aged 58+/-12 mo) were tested for visual
      acuity (VA) and assessed for their emergent literacy skills [three standard tests
      (letter/word reading skills, receptive vocabulary and phonological awareness) and
      an experimental test of emergent orthography]. Parents completed a survey of
      family demographics, health/developmental concerns and home literacy experiences.
      Visual motor and visual perceptual skills tests were used to assess any visual
      cognitive differences. RESULTS: There were no differences in single letter VA for
      hyperopes and emmetropes and crowded letters for the right eye. Crowding effects
      were significantly greater in the left eye for hyperopes (t (30)=-2.74, p=0.01),
      with two of the hyperopes showing abnormal crowding. Hyperopes lagged behind
      emmetropes in letter and word recognition ability (Mann-Whitney U=72, p=0.049),
      receptive vocabulary (F(1,30)=9.64, p=0.004), and emergent orthography
      (F(1,29)=5.43, p=0.03). The groups did not differ in phonological awareness
      skills (F(1,29)=0.39, p=0.54). No statistically significant differences between
      the two groups were found for visual motor or visual perceptual skills, age, and
      some family variables known to contribute to emergent literacy skills.
      CONCLUSIONS: In this pilot study, uncorrected hyperopic children, ages 4 to 7
      years, show reduced performance on tests of letter and word recognition,
      receptive vocabulary, and emergent orthography and crowded VA, despite no
      difference in phonological awareness skills, visual cognitive skills, and other
      family variables known to affect the acquisition of literacy skills. The
      relationship between hyperopia and the poorer progress in emergent literacy is
      complex, and it is not clear if the relationship is causal, and whether the
      hyperopes will catch up to the emmetropes with time.

PMID- 18043423
TI  - Rotational stability of toric soft contact lenses during natural viewing
      conditions.
AB  - PURPOSE: To compare objectively the rotational stability of two differently
      designed toric soft contact lenses over a range of natural viewing conditions
      using a novel infrared, video-based technique. METHODS: Two contact lenses using
      different methods of stabilization were assessed: Accelerated Stabilization
      Design (ACUVUE ADVANCE for ASTIGMATISM) and Lo-Torque Design (B&L SofLens Toric).
      Four tasks involving saccades were performed: settling time with free viewing,
      reading, visual search, and execution of large versional tasks. Lens position
      (degrees of rotation) was continuously recorded with a head mounted, infrared,
      video-based system and a digital photo slit-lamp in 20 adult subjects. All
      measurements were obtained from the left eye under binocular viewing conditions
      with contact lenses on both eyes. RESULTS: The ACUVUE lens was significantly more
      stable during the settling time and large saccadic versional tasks than the
      SofLens. For the two other tasks (reading, visual search), performance was
      similar. CONCLUSION: The ACUVUE design was superior in stability for two of the
      four conditions tested. This resulted in a more stable lens immediately after
      insertion as well as during some visual tasks involving either naturally
      occurring or programmed large versional eye movements. Both lens designs provided
      acceptable performance in terms of induced astigmatism produced by off-axis
      rotation.

PMID- 18043424
TI  - Vision evaluation of eccentric refractive correction.
AB  - PURPOSE: This study investigates the benefits of eccentric refractive correction
      to resolution and detection thresholds in different contrasts for seven subjects
      with central visual field loss (CFL) and for four healthy control subjects with
      normal vision. METHODS: Refractive correction in eccentric viewing angles, i.e.,
      the preferred retinal location for the CFL subjects and 20 degrees off-axis for
      the control subjects, was assessed by photorefraction with the PowerRefractor
      instrument and by wavefront analysis using the Hartmann-Shack principle. The
      visual function with both eccentric and central corrections was evaluated using
      number identification and grating detection. RESULTS: For the CFL subjects, the
      resolution and detection thresholds varied between individuals because of
      different preferred retinal locations and cause of visual field loss. However,
      all seven CFL subjects showed improved visual function for resolution and
      detection tasks with eccentric correction compared with central correction. No
      improvements in high-contrast resolution were found for the control subjects.
      CONCLUSIONS: These results imply that optical eccentric correction can improve
      the resolution acuity for subjects with CFL in situations where healthy eyes do
      not show any improvements.

PMID- 18043425
TI  - Tolerance to prism induced by readymade spectacles: setting and using a standard.
AB  - PURPOSE: To determine first how much induced horizontal and vertical prism could
      be comfortably tolerated with readymade spectacle wear. Ultimately, the purpose
      is to develop a guide for dispensing decisions for blindness prevention programs
      in low-resource countries. METHODS: Nine participants each wore plano spectacles
      with differing prism power for 8 h (plano control). If visual discomfort could
      not be tolerated, participants removed the spectacles, noting duration of wear
      and reason for discontinuation. Distance and near visual comfort were rated, and
      participants asked if they would be able to adapt to wearing the spectacles.
      RESULTS: On average, half of the wearing time was spent on concentrated near
      viewing tasks. The highest prism powers (1 Delta BU, 2 Delta BO, 2 Delta BI)
      could not be worn for 8 h by the majority of participants. Comfort ratings at
      near (similar to those at distance) were statistically significantly different
      when the highest prism power was compared with each of the lower powers (vertical
      prism: both the control and 0.5 Delta differed from 1 Delta; horizontal prism:
      the control, 0.5 Delta and 1 Delta all differed from 2 Delta). CONCLUSIONS: Most
      spectacle wearers would likely comfortably tolerate <or=0.5 Delta vertical,
      <or=1.0 Delta base out, or <or=1.0 Delta base in induced prism. A guide to the
      maximum interpupillary distance/optical center distance disparities likely to be
      comfortably tolerated with varying spectacle powers was formulated. Powers up to
      +/-1.50 DS are unlikely to have sufficient lens decentration to cause discomfort.
      This small study supports the feasibility of using readymade spectacles in low
      resource settings even though optical center distance may be different to the
      interpupillary distance of the wearer. It would seem that fear of visual
      discomfort because of induced prism need not preclude the use of readymade
      spectacles, potentially correcting about 75% of refractive error and presbyopia,
      mostly with powers +3.00 to -3.00 DS. Further study is needed to more fully
      address these issues.

PMID- 18043426
TI  - Power vectors versus power matrices, and the mathematical nature of dioptric
      power.
AB  - Representation of astigmatic dioptric power as a power vector is satisfactory for
      basic operations such as summing and averaging powers. However, power vectors do
      not fully characterize the nature of dioptric power and are, therefore,
      unsatisfactory for representing power in general. The purpose of this note is to
      make the case that it is the power matrix instead that is proper for the
      representation of power in general. The mathematical nature of dioptric power is
      examined.

PMID- 18043427
TI  - Reliability of microdrill stapedotomy: comparison with pick stapedotomy.
AB  - OBJECTIVE: To assess the hearing outcomes and complications of the microdrill and
      pick stapedotomy techniques. PATIENTS: We assessed 123 primary otosclerosis
      operation in 103 patients who had more than 1 year follow-up (71 microdrill; 52
      pick stapedotomies). There were 87 women and 36 men in the study group (mean age,
      44 +/- 11.2 years) at surgery. INTERVENTION: Stapedotomy for otosclerosis. MAIN
      OUTCOME MEASURES: Pure tone hearing thresholds and clinical evaluation for
      complications. RESULTS: In the microdrill group, preoperative mean air conduction
      was 61 dB, and mean bone conduction was 27 dB, postoperatively, these values
      improved to 31 dB and 16 dB, respectively. In the pick group, mean air conduction
      was 61 dB, and mean bone conduction was 27 dB, which improved postoperatively to
      33 dB and 18 dB, respectively. Postoperative hearing gains were similar in both
      groups (p > 0.005). The mean postoperative gain in bone conduction was
      significant (p < 0.001) in each group: 11 dB in the microdrill group and 9 dB in
      the pick group, with no significant difference between the two groups. The
      preoperative air-bone gap was 34 dB in both groups, and improved to 15 dB in
      both. Complication rates were similar. CONCLUSION: The microdrill and pick
      stapedotomy techniques produced similar hearing results and complication rates.
      Within the limitations of the present study, we found no evidence of microdrill
      induced acoustic trauma. The microdrill can be a useful technique in performing a
      stapedotomy and seems to produce similar results to those associated with pick
      stapedotomy.

PMID- 18043428
TI  - Feasibility of auditory cortical stimulation for the treatment of tinnitus.
AB  - OBJECTIVES: To investigate the feasibility and safety of an implantable epidural
      cortical stimulator for the treatment of severe tinnitus. STUDY DESIGN:
      Prospective, controlled, single-blinded study of cortical stimulation for 4
      weeks, and then an open-label stimulation period. SETTING: Tertiary care referral
      center. PATIENTS: Adults (n = 8) with constant tinnitus of at least 1 year with a
      tinnitus reaction questionnaire score greater than 33. Tinnitus was predominantly
      unilateral with a frequency less than 8,000 Hz. INTERVENTIONS: Surgical
      implantation of an investigational epidural electrode over the posterior superior
      temporal gyrus using functional magnetic resonance imaging targeting. A 2-week
      stimulation period alternated with a 2-week sham period in random order to which
      subjects were blinded. This was followed by continuous stimulation with parameter
      adjustments to maximize tinnitus suppression. MAIN OUTCOME MEASURE: Subjective
      rating of tinnitus severity, loudness, and device efficacy. Objective measures of
      hearing thresholds, tinnitus frequency, loudness, and minimum masking levels.
      Outcome measures using the Tinnitus Handicap Questionnaire, Tinnitus Reaction
      Questionnaire, and Beck Depression Inventory. RESULTS: There were no effects of
      stimulation during the 4-week blinded period. With continuous chronic
      stimulation, 2 patients had persistent reduction of pure-tone tinnitus, and 6
      patients had short periods of total tinnitus suppression. Significant
      improvements in the Beck Depression Inventory and tinnitus questionnaires were
      found, although objective measures of tinnitus loudness remained fairly stable.
      No surgical or stimulation-related complications were noted. CONCLUSION: Chronic
      electrical stimulation of the secondary auditory cortex seems safe and warrants
      further investigation as a potential therapeutic intervention for the suppression
      of tinnitus.

PMID- 18043429
TI  - Assessment of changes in cochlear function with pneumolabyrinth after middle ear
      trauma.
AB  - OBJECTIVE: To describe a case of pneumolabyrinth secondary to tympanic
      membrane/ossicular trauma and the subsequent recovery of sensorineural hearing
      loss managed with conservative measures. PATIENTS: A 15-year-old boy presented to
      an outside hospital with signs and symptoms of acute hearing loss, vertigo, and
      tinnitus after penetrating injury to his right tympanic membrane. In addition,
      computed tomography demonstrated air density within the vestibule. INTERVENTIONS:
      The patient was managed conservatively with bed rest, avoidance of straining,
      corticosteroids, and antibiotics. MAIN OUTCOME MEASURES: Computed tomography,
      audiologic testing. RESULTS: Patient recovered near-normal hearing subjectively.
      There was closure of the air-bone gap (<or=20 dB) along with resolution of air
      within vestibule. CONCLUSION: We presented a case of a patient with
      pneumolabyrinth secondary to penetrating trauma to his tympanic membrane. With
      supportive treatment, air within the labyrinth resorbed, and the patient
      recovered sensorineural function. Comparing with the mixed successes of surgical
      repairs, we propose that initial management for traumatic pneumolabyrinth should
      be first treated conservatively in the absence of worsening symptoms.

PMID- 18043430
TI  - Hearing results for ossicular reconstruction using a cartilage-connecting
      hydroxyapatite prosthesis with a spearhead.
AB  - OBJECTIVE: Assessment of the efficacy of ossicular reconstruction using a
      cartilage-connecting hydroxyapatite prosthesis designed with a spearhead to
      reduce extrusion and dislocation of the implant. PATIENTS: All patients
      undergoing ossicular reconstruction after chronic ear surgery, connecting the
      cartilage to the prosthesis, with a minimum of 1 year of postoperative follow-up.
      MAIN OUTCOME MEASURES: Postoperative change in pure-tone averages. Air-bone gap
      closures, and implant extrusion rates. RESULTS: Overall mean pure-tone averages
      improved by 12.2 dB (ranged between -40 and 60 dB). In total, 68.4% of the
      patients achieved an air-bone gap less than 20 dB. Gains in the mean air
      conduction thresholds were 9.5 dB in cases of partial ossicular reconstruction
      and 14.9 dB in cases with total ossicular reconstruction (p < 0.05). The overall
      extrusion rate was 4.21%. CONCLUSION: The cartilage-connecting hydroxyapatite
      prosthesis with a spearhead was found to restore hearing to a satisfactory level.
      The extrusion rate was relatively low. The cartilage-connecting hydroxyapatite
      prosthesis with a spearhead is an effective ossicular implant and offers an
      attractive alternative for ossicular reconstruction, particularly for total
      ossicular reconstructions.

PMID- 18043431
TI  - Auditory midbrain implant: histomorphologic effects of long-term implantation and
      electric stimulation of a new deep brain stimulation array.
AB  - HYPOTHESIS: Chronic implantation and electric stimulation with a human prototype
      auditory midbrain implant (AMI) array within the inferior colliculus achieves
      minimal neuronal damage and does not cause any severe complications. BACKGROUND:
      An AMI array has been developed for patients with neural deafness and, based on
      animal studies, has shown to possess potential as an auditory prosthesis in
      humans. To investigate the safety of the AMI for clinical use, we characterized
      the histomorphologic effects of chronic implantation and stimulation within its
      target structure, the inferior colliculus. METHODS: Eight cats were chronically
      implanted for 3 months, and histologic sections were analyzed to assess long-term
      tissue effects. Four of the 8 cats were additionally stimulated for 60 days (4
      h/d) starting 4 weeks after implantation to assess if clinically relevant stimuli
      further affected the tissue response. RESULTS: In general, both neurons and
      neuropil surrounding the implant track were apparently unaffected, whereas a
      fibrillary sheath (approximately 50 microm thick) developed around the array.
      There was a significant decrease in neuron density 50 to 100 microm away from the
      track with a significantly elevated number of glial cells out to approximately
      250 to 350 microm. Chronic stimulation seemed to improve the tissue response and
      neuronal survival around the implant, although further studies are needed to
      confirm this finding. CONCLUSION: The histomorphologic effects and extent of
      neuronal damage observed for our AMI array are similar to those of other neural
      implants currently and safely used in humans. The minimal tissue damage
      surrounding the implanted array is encouraging with regard to the safety of the
      array for human use.

PMID- 18043432
TI  - Histopathologic changes of contralateral human temporal bone in unilateral
      Meniere's disease.
AB  - HYPOTHESIS: To disclose the histopathologic findings in the contralateral
      temporal bone in unilateral Meniere's disease. BACKGROUND: Several functional
      studies reported abnormal findings in the contralateral ears in patients with
      unilateral Meniere's disease. METHODS: This study involved quantitative analysis,
      including the number of spiral ganglion cells, the loss of cochlear hair cells,
      the area of stria vascularis, and the density of fibrocytes in the spiral
      ligament. It included 14 temporal bones from 7 subjects with bilateral Meniere's
      disease, 30 temporal bones from 15 subjects with unilateral Meniere's disease,
      and 17 age-matched normal control temporal bones from 12 subjects. RESULTS: The
      mean number of spiral ganglion cells in the contralateral temporal bones in
      patients with unilateral Meniere's disease was 17,376.0 and was significantly
      lower than that in normal controls. The mean loss of inner and outer hair cells
      in the contralateral temporal bones in patients with unilateral Meniere's disease
      was significantly greater than that in normal controls in all turns. The stria
      vascularis was severely atrophic and degenerated in patients with Meniere's
      disease. The mean area of stria vascularis in contralateral temporal bones in
      patients with unilateral Meniere's disease was significantly smaller than normal
      controls. There was no significant difference in the density of fibrocytes in the
      spiral ligament between the diseased side and the contralateral side in patients
      with unilateral Meniere's disease and between normal control and contralateral
      side. CONCLUSION: The contralateral inner ear in patients with unilateral
      Meniere's disease has significantly more damage compared with inner ears of
      normal controls.

PMID- 18043433
TI  - Revision surgery for residual or recurrent vestibular schwannoma.
AB  - OBJECTIVE: Assess the requirement for and describe the complication rates of
      revision surgery for vestibular schwannoma. STUDY DESIGN: Retrospective case
      review. SETTING: Tertiary referral center. PATIENTS: Patients undergoing surgery
      for vestibular schwannoma by the Manchester Neurotology Service between 1978 and
      2004. INTERVENTION: Surgery. MAIN OUTCOME MEASURE(S): The presence of recurrent
      or residual tumor; necessity for further treatment; complications from revision
      surgery. RESULTS: Primary surgery was undertaken on 1,037 tumors, with 866 total
      (19 recurred), 128 near-total, and 43 subtotal removals. Further treatment was
      performed for 4 recurrent, 2 near-total, and 11 subtotal excised tumors. Thirty
      five revision operations resulted in 14 total (1 recurred), 8 near-total, and 13
      subtotal removals. Further treatment was required for 3 near-total and 6 subtotal
      excisions. Poor preoperative facial function (House-Brackmann Grades 4-6) was
      present in 9 of the 35 patients. A further 10 deteriorated by at least 3 grades
      by 1 year postoperatively. Other complications of revision surgery included 3
      patients with cerebrospinal fluid leaks, a postoperative hematoma requiring
      evacuation, 2 cerebrovascular accidents, and 2 patients with new cranial nerve
      deficits. CONCLUSION: Most residual tumors after primary surgery are successfully
      managed with watch and rescan. Tumor fragment size is the greatest determinant of
      revision treatment. After revision surgery, tumor regrowth is much less
      predictable. Revision surgery is usually considerably more difficult than primary
      surgery, with a higher complication rate, particularly with regard to the facial
      nerve. Changing the approach for revision surgery may confer an advantage to
      facial nerve function.

PMID- 18043434
TI  - Distribution of nonvestibular cranial nerve schwannomas in neurofibromatosis 2.
AB  - OBJECTIVE: To describe the prevalence and location of cranial nerve schwannomas,
      other than bilateral vestibular schwannoma, in patients with neurofibromatosis 2
      (NF2). The NF2 Natural History Consortium prospectively gathered cranial magnetic
      resonance imaging for 83 patients across 3 annual evaluations. The time between
      the first and last evaluation was approximately 3 years. RESULTS: Forty-two
      patients (51%) had nonvestibular cranial nerve schwannomas (NVSs). Of these, 25
      (60%) also had cranial meningiomas. Twenty-one of those without NVS (25% of 83)
      had at least 1 meningioma. The average size of the NVS was 0.4 cubic centimeters.
      Overall, there was no significant change in NVS size from Year 1 to Year 3 or
      from Year 1 to Year 2. The most common locations of the NVS were occulomotor and
      trigeminal. A family history of NF2 did not predict NVS location or growth.
      CONCLUSION: Nonvestibular cranial nerve schwannoma usually affect cranial nerves
      III and V, as was the case in our NF2 sample. Fortunately, neuropathies
      associated with these tumors are rare. In contrast, lower cranial nerve
      schwannomas, although also rare, are associated with swallowing difficulty,
      aspiration, and other sequelae.

PMID- 18043435
TI  - Helper-dependent adenovirus-mediated gene transfer into the adult mouse cochlea.
AB  - BACKGROUND: Gene therapy may provide a way to restore cochlear function to deaf
      patients. The most successful techniques for cochlear gene therapy have been
      injection of early-generation adenoviral vectors into scala media in guinea pigs.
      However, it is important to be able to perform gene therapy research in mice
      because there is wide availability of transgenic strains with hereditary hearing
      loss. PURPOSE: We demonstrate our technique for delivery of a third-generation
      adenoviral vector, helper-dependent adenovirus (HDAd), to the adult mouse
      cochlea. METHODS: Mice were injected with an HDAd that contained a reporter gene
      for either beta-galactosidase or green fluorescent protein into scala media.
      After 4 days, the cochleae were harvested for analyses. Auditory brainstem
      response monitoring of cochlear function was performed before making a
      cochleostomy, after making a cochleostomy, and before killing the animal.
      RESULTS: Beta-galactosidase was identified in the spiral ligament, the organ of
      Corti, and spiral ganglion cells by light microscopy. Green fluorescent protein
      epifluorescence was assessed in whole-mount organ of Corti preparations using
      confocal microscopy. This demonstrated transduction of inner hair cells, outer
      hair cells, and supporting cells. Paraffin-embedded cross sections similarly
      revealed gene transduction within the organ of Corti. Threshold shifts of 39.8 +/
      5.4 and 37.7 +/- 5.5 dB were observed in mice injected with HDAd or control
      buffer, respectively. CONCLUSION: The technique of scala media HDAd injection
      reliably infects the adult mouse cochlea, including cells within the organ of
      Corti, although the procedure itself adversely affects hearing.

PMID- 18043436
TI  - Neural network and "ganglion" formations in vitro: a video microscopy and
      scanning electron microscopy study on adult cultured spiral ganglion cells.
AB  - HYPOTHESIS: To analyze if adult-dissociated spiral ganglion cells may be
      propagated in vitro for later use in transplantation models to form integrated
      neural networks. BACKGROUND: Hearing loss is often associated with primary or
      secondary spiral ganglion cell degeneration. New strategies for cell repair and
      tissue engineering warrants further elucidation of the regenerative capacity of
      the auditory nerve. METHODS: We used in vitro/in video microscopy in combination
      with immunocytochemistry and field emission scanning electron microscopy to
      analyze neural development and network formation from dissociated adult guinea
      pig spiral ganglion cells. Cells were cultured in serum-free medium and in the
      presence of brain-derived neurotrophic factor, neurotrophin 3, and glia cell line
      derived neurotrophic factor for up to 8 weeks. RESULTS: Time-lapse video
      microscopy and scanning electron microscopy exposed the propagation of auditory
      neurons and the role of neural growth cones in axon locomotion, fasciculation,
      and nuclear migration, often ensuing in cell congregation (ganglion-like
      formations) during network formation. Axons were sometimes ensheathed by
      adjoining S-100/glia fibrillary acidic protein-expressing cells. A few expanding
      neurons were nestin positive and sometimes incorporated the markers of
      proliferating cells Ki67 and 5'-bromo-2-deoxyuridine. Neurons expressed the
      markers and transcription factors for neural development neurogenin 1, neurogenic
      differentiation factor 1, Brn3a, and GATA binding protein 3, as well as the
      neural markers beta-III tubulin, NeuN, and neurofilament 160 during this process.
      CONCLUSION: This method of culturing and expanding spiral ganglion neurons in
      vitro may be useful in further studies of cell transplantation models aiming to
      restore the injured inner ear.

PMID- 18043437
TI  - Localization of congenital tegmen tympani defects.
AB  - OBJECTIVE: This study sets out to demonstrate the normal developmental steps of
      the tegmen tympani and thus explains the typical localization of congenital
      tegmental defects. SPECIMENS: For this study, 79 macerated and formalin-fixed
      human temporal bones from 14th fetal week to adults were observed and prepared.
      INTERVENTION: Macroscopic and microscopic examination of the prenatal and
      postnatal changes of the tegmen tympani during its development. MAIN OUTCOME
      MEASURE: Temporal bones from 14th fetal week to adults underwent descriptive
      anatomic studies to understand the normal development of the tegmen tympani and
      to find a possible cause of its congenital defects. RESULTS: The medial part of
      the tegmen tympani develops from the otic capsule during chondral ossification,
      thus forming the tegmental process of the petrous part. The lateral part shows
      membranous ossification. The tegmental process cases a temporary bony dehiscence
      lateral to the geniculate ganglion between the 23rd and 25th fetal week.
      CONCLUSION: Congenital defects develop near the geniculate ganglion and seem to
      be due to an incomplete development of tegmental process of otic capsule. Because
      of that, congenital lesion of the tegmen tympani can be defined as an inner ear
      defect.

PMID- 18043438
TI  - Intratympanic versus intravenous delivery of methylprednisolone to cochlear
      perilymph.
AB  - OBJECTIVE: To compare methylprednisolone concentrations in the perilymph of the
      human ear and in plasma after intratympanic (IT) or intravenous (IV)
      administration. METHODS: Methylprednisolone concentrations in the perilymph of
      patients during cochlear implantation were compared after 3 dosing strategies of
      methylprednisolone solution for injection (40 mg/ml): 1) IT administration of up
      to 40 mg was injected into the middle ear through the external auditory canal via
      a 27-gauge needle passed through a small anterosuperior myringotomy; 2) IV
      administration of 1 mg/kg was given as a single injection over 30 seconds; 3) IV
      administration of 10 mg/kg was infused over 30 minutes. Perilymph (single sample,
      approximately 20 microL) was sampled using a needle passed through the round
      window membrane, from 0.5 to 3 hours after dosing. In most patients, simultaneous
      blood sampling was performed. Methylprednisolone concentrations were measured by
      high-performance liquid chromatography with a limit of quantification of 0.001
      mg/L. RESULTS: In 39 patients studied, 33 perilymph samples were suitable for
      measurement, along with 26 plasma samples. Median perilymph concentrations were
      6.7 mg/L (n = 18; range, 0.2-89.4 mg/L) after IT administration, 0.053 mg/L (n =
      8; range, 0-0.47 mg/L) after IV injection of 1 mg/kg, and 0.2 mg/L (n = 7; range,
      0.067-3.1 mg/L) after IV infusion of 10 mg/kg. The median perilymph
      concentrations were 126-fold higher after the IT administration than after 1
      mg/kg IV (p = 0.0003) and 33-fold higher than after 10 mg/kg IV infusion (p =
      0.0045). Plasma concentrations after IT administration were 16-fold lower than
      after IV administration of 1 mg/kg (p = 0.0006), and 136-fold lower than after IV
      infusion of 10 mg/kg (p = 0.0006). CONCLUSION: IT administration of
      methylprednisolone in humans results in much higher perilymph concentrations and
      much lower systemic concentrations than IV administration.

PMID- 18043439
TI  - An arachnoid cyst of the fallopian canal.

PMID- 18043440
TI  - Re: "Silicone allergy: a new cause for cochlear implant extrusion and its
      management".

PMID- 18043442
TI  - Severe bronchiolitis and respiratory syncytial virus among young children in
      Hawaii.
AB  - BACKGROUND: Lower respiratory tract infections are a leading cause of
      hospitalization and mortality among children worldwide. Our objective was to
      describe the incidence and epidemiology of severe bronchiolitis, respiratory
      syncytial virus (RSV), and pneumonia among children in Hawaii. METHODS:
      Retrospective analysis of the patient-linked hospital discharge data associated
      with bronchiolitis, RSV, and pneumonia among Hawaii residents younger than 5
      years of age during 1997 through 2004 using the Hawaii State Inpatient Database.
      RESULTS: During 1997 through 2004, the average annual incidence rates for
      bronchiolitis, RSV, and pneumonia were 3.8, 2.7, and 6.8 per 1000 children
      younger than 5 years, respectively. The incidence of each condition was higher
      for infants younger than 1 year (15.1, 9.8, and 15.9 per 1000 infants,
      respectively) than the incidence for children 1-4 years of age, and higher for
      boys compared with girls. The incidence of each condition was highest among
      Native Hawaiian and other Pacific Islander children compared with children of
      other race groups living in Hawaii. Most hospitalizations occurred during the
      months of October through February. Estimated median hospital charges were $4806
      (bronchiolitis), $5465 (RSV) and $5240 (pneumonia), with overall average annual
      charges of $11.5 million. CONCLUSION: The incidence and hospitalization rates for
      bronchiolitis, RSV, and pneumonia among children younger than 5 years of age in
      Hawaii were low; the corresponding hospitalization rates were lower than those
      for the general U.S. population. However, the hospitalization rates for each
      condition among Hawaiian and other Pacific Islander children were much higher
      than those for other race groups or for the U.S. population.

PMID- 18043443
TI  - Intravenous palivizumab and ribavirin combination for respiratory syncytial virus
      disease in high-risk pediatric patients.
AB  - BACKGROUND: Risk factors for severe respiratory syncytial virus (RSV) disease
      include prematurity, congenital heart disease, chronic lung disease, and
      immunocompromised states. There is no consensus concerning the most effective
      therapy for severe RSV infection in high-risk patients. Palivizumab is approved
      for prevention of RSV disease, and ribavirin is approved for treatment of RSV
      infections but its efficacy in high-risk patients has not been conclusively
      established. METHODS: Retrospective chart review of RSV infected children treated
      with intravenous palivizumab and ribavirin in a pediatric hospital from 2001 to
      2005. RESULTS: : Twenty male and 11 female patients with a median age of 23.4
      months, hospitalized for RSV infection were treated with intravenous palivizumab
      from October 2001 through July 2005. Mean dose was 14.93 (SD = 0.68) mg/kg.
      Twenty-five patients (80%) also received ribavirin, 22 of whom by aerosolization.
      Common baseline diagnoses were malignancy (n = 15), congenital heart disease (n =
      5), and prematurity (n = 5). Included above are 1 cardiac and 6 hematopoietic
      stem cell transplant recipients. Eighteen (58%) patients had signs of lower
      respiratory tract infection, 17 were hypoxemic, 10 required intensive care unit
      (ICU) admission, and 5 were intubated. Twenty-nine (93.6%) patients survived and
      2 died. No adverse events attributed to intravenous palivizumab or ribavirin
      administration were observed. CONCLUSIONS: Treatment of RSV-infected high-risk
      children with intravenous palivizumab alone or in combination with ribavirin was
      well tolerated and associated with decreased mortality compared with previous
      reports.

PMID- 18043444
TI  - Interleukin (IL)-18 polymorphism 133C/G is associated with severe respiratory
      syncytial virus infection.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of bronchiolitis
      in infants. During the course of RSV infection, predominant T helper cell (TH) 2
      response is associated with disease progression, whereas predominant TH1 reaction
      provides convalescence. Interleukin (IL)-18 plays an important role in adjusting
      the TH1/TH2 immune response to viral infections. Thus, we tested the hypothesis
      that polymorphisms in IL-18 were associated with severe RSV-associated diseases.
      METHODS: We chose to study the promotor polymorphisms -607A/C (rs1946518) and 
      137G/C (rs187238), the 2 exon polymorphisms 113T/G (rs360718) and 127C/T
      (rs360717), and 2 intron polymorphisms 5304A/G (rs795467) and 133G/C (rs360721)
      within the IL-18 gene. Genotyping was performed on 154 children with severe RSV
      infection as defined by strict clinical criteria and on 270 controls. Statistical
      analyses of single polymorphisms made use of the Armitage's trend test,
      haplotypes were calculated with FASTEHPLUS and FAMHAP. RESULTS: -133G/C showed
      association with severe RSV infection (P = 0.043). The association was further
      supported by haplotype analyses with all 6 polymorphisms (P < 0.00001 for
      association with RSV). CONCLUSIONS: This study indicates possible involvement of
      IL-18 in the determination of severe RSV-associated diseases. Defining the
      genetic basis of RSV bronchiolitis might help us in identifying new drug targets
      for a more specific therapy. In addition, it might enable an early identification
      of children at risk for RSV bronchiolitis and thus make a selective prevention
      feasible.

PMID- 18043445
TI  - Safety and efficacy of the pentavalent human-bovine (WC3) reassortant rotavirus
      vaccine in healthy premature infants.
AB  - BACKGROUND: Premature infants seem to be at greater risk of hospitalization from
      rotavirus gastroenteritis than term infants. Safety and efficacy of the
      pentavalent human-bovine (WC3) reassortant rotavirus vaccine were assessed in
      premature infants enrolled in the large-scale, blinded, placebo-controlled
      rotavirus efficacy and safety trial (REST). METHODS: Healthy infants 6-12 weeks
      of chronologic age at study entry were randomized to receive 3 oral doses of
      pentavalent rotavirus vaccine or placebo at 4- to 10-week intervals. Infants born
      at < or =36 weeks of gestational age were eligible if thriving at the time of
      enrollment. Safety and efficacy were retrospectively assessed in these premature
      infants comparing vaccine with placebo recipients. Cases of rotavirus
      gastroenteritis were defined as forceful vomiting and/or > or =3 watery or looser
      than-normal stools within a 24-hour period, accompanied by detection of rotavirus
      antigen in the stool. RESULTS: A total of 2070 infants between 25 and 36
      gestational weeks received at least 1 dose of vaccine or placebo; 1005 vaccine
      recipients and 1061 placebo recipients were evaluable for safety. Serious adverse
      events occurred in 55 vaccine recipients (5.5%) and 62 placebo recipients (5.8%).
      In a nested substudy of 308 premature infants evaluable for detailed safety (154
      in each group), the frequencies of fever, diarrhea, vomiting, and irritability
      were comparable between vaccine and placebo recipients. Overall, 3 doses of the
      pentavalent vaccine reduced the rate of hospitalizations and emergency department
      visits in premature infants due to rotavirus gastroenteritis by 100% (95% CI:
      82.2-100) compared with placebo. The vaccine also prevented 73.0% (95% CI: -2.2
      95.2) of rotavirus gastroenteritis cases of any severity. CONCLUSIONS: In this
      post hoc analysis of healthy premature infants, the pentavalent rotavirus vaccine
      was generally well-tolerated and substantially reduced rotavirus-attributable
      hospitalizations and emergency department visits compared with placebo. Overall,
      vaccine safety and efficacy seemed to be generally comparable to the results in
      the REST study population as a whole. These results support vaccinating healthy
      premature infants on the same schedule as term infants.

PMID- 18043446
TI  - Immunogenicity and safety of a pneumococcal conjugate 7-valent vaccine in infants
      with sickle cell disease.
AB  - OBJECTIVES: To evaluate safety and immunogenicity of the pneumococcal 7-valent
      conjugate vaccine (PCV7) when administered to infants with sickle cell disease
      (SCD) at 2, 3, and 4 months of age with a booster dose of a 23-valent
      pneumococcal polysaccharide vaccine (PS-23) at 15 to 18 months of age. METHODS:
      This open-label multicenter study in France enrolled 2-month-old infants with
      SCD. Blood samples for the determination of antibody concentrations to vaccine
      serotypes were obtained immediately before and 1 month after the primary
      immunization, and before and 1 month after the PS-23 booster. Local and systemic
      reactions were recorded on diary cards. RESULTS: Of the 51 infants enrolled, 49
      received primary immunization and 46 received the booster dose. After primary
      immunization > or =95% of the subjects had antibody titers > or =0.35 microg/mL
      for the 7 serotypes. After boosting, geometric mean concentrations were high for
      all serotypes, ranging from 6.32 microg/mL (serotype 18C) to 29.49 microg/mL
      (serotype 4). Except for 1 case after administration of the booster dose, all
      fevers reported were less than 39 degrees C. No vaccine-related serious adverse
      events were reported. CONCLUSIONS: PCV7 administered at 2, 3, and 4 months of age
      in infants with SCD was well-tolerated, highly immunogenic, and primed for immune
      memory as indicated by the dramatic response to the PS-23 dose administered at 15
      18 months in this study. However, the current recommended schedule is to boost
      with the PCV7 at 12-15 months of age and for these high-risk children, to enlarge
      the protection with a subsequent PS-23 dose at 2 years of age.

PMID- 18043447
TI  - Unexpected individual clinical site variation in eradication rates of group a
      streptococci by penicillin in multisite clinical trials.
AB  - BACKGROUND: Previously, we reported an unexpectedly large percentage of failures
      by penicillin to eradicate group A streptococci (GAS) from the upper respiratory
      tract. Because penicillin has been the recommended therapy for the treatment of
      GAS pharyngitis, our report prompted controversy. Data from clinical trials in
      which our laboratory has participated demonstrated marked variation in GAS
      eradication rates among clinical sites. The reasons for such variation have never
      been adequately examined. We performed statistical analyses of site variation in
      eradication rates to assess the potential effect on reported reduced penicillin
      efficacy. METHODS: Penicillin GAS eradication rates were compared using data from
      4 large multisite pharyngitis treatment trials (75 clinical sites; 1158
      subjects). Variation in eradication rates among clinical sites was statistically
      evaluated [chi(2) tests and generalized estimating equation (GEE) regression
      models]. RESULTS: There was significant site-to-site variation in GAS eradication
      rates in each of the trials (range, 17-100%; P < 0.005) as well as between
      separate trials (mean range, 58-69%; P < 0.033). GEE modeling indicated that GAS
      eradication rates were significantly higher for clinical sites participating in
      more than one clinical trial. CONCLUSIONS: The statistically significant site-to
      site variation in penicillin eradication rates was related to factors
      (dependencies) at individual sites. Such factors may affect assessment of
      therapeutic efficacy and indicate a necessity for considering clinical site
      variation before reporting pooled efficacy data from multiple sites; combined
      data may result in misleading clinical implications. This is the first report
      documenting significant variation resulting from individual clinical site-related
      factors and offers a possible explanation for reduced penicillin eradication.

PMID- 18043448
TI  - Incidence of tonsillectomy in Denmark, 1980 to 2001.
AB  - BACKGROUND: Tonsillectomy is one of the most frequent operations performed on
      children and young adults, but little is known regarding its distribution by age,
      sex, and calendar period. METHODS: We designed a population-based cohort study
      including all Danish residents from 1980 to 2001 to describe national incidence
      figures for tonsillectomy. Persons undergoing tonsillectomy were identified in
      the Danish National Patient Registry and from the Danish Health Security System.
      Overall, the cohort consisted of 6.3 million persons, who were followed up for
      106.9 million person-years. RESULTS: During the study period 153,212 patients had
      tonsillectomies, comprising 84,831 females and 68,381 males. The age-specific
      incidence of tonsillectomy peaked at 4 years of age for both boys and girls, with
      9.7 and 6.9 tonsillectomies per 1000 person-years, respectively. A second peak
      emerged during teenage years in both sexes, being highest among girls with 8.6
      tonsillectomies per 1000 person-years at 16 years of age and 3.1 tonsillectomies
      per 1000 person-years among 17-year-old boys. The cumulative risk of
      tonsillectomy during the first 20 years of life increased from 7.9% among females
      and 6.0% among males in 1980 to 9.2% and 7.7%, respectively, in 2001. Over 90% of
      the patients less than 20 years of age registered at hospital with chronic
      disease of the tonsils had tonsillectomies within a year. CONCLUSIONS: The
      incidence of tonsillectomy revealed significant gender differences. Furthermore,
      2 incidence peaks emerged at age 4 years and age 16-17 years. The second peak in
      adolescence was particularly pronounced for females and is unexplained.

PMID- 18043449
TI  - Increase of the USA300 clone among community-acquired methicillin-susceptible
      Staphylococcus aureus causing invasive infections.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is a
      predominant cause of community-acquired (CA) infection in the United States. We
      compared clinical characteristics of children with USA300 versus non-USA300 CA
      methicillin-susceptible S. aureus (CA-MSSA) invasive infections at Texas
      Children's Hospital (TCH). METHODS: Medical records were reviewed from children
      with invasive CA-MSSA infections at TCH between August 1, 2001 and September 30,
      2006. Isolates were characterized by pulsed-field gel electrophoresis and
      polymerase chain reaction for Panton-Valentine leukocidin genes (pvl). RESULTS:
      Invasive CA-MSSA infections increased from 14 in year 1 to 36 in year 5 (5-year
      total = 122 patients). Among the CA-MSSA isolates available for typing in the 5
      year period, USA300 MSSA strains increased from 14% (2 of 14) to 35% (11 of 31)
      (P = 0.03). USA300 MSSA strains were more likely than non-USA300 MSSA strains to
      be nonsusceptible to erythromycin [66% (19 of 29) versus 28% (25 of 88); P <
      0.01]. Osteomyelitis cases increased from 43% (6 of 14) in year 1 to 67% (24 of
      36) in year 5. The majority of pvl(+) MSSA isolates were USA300 (71% (25 of 35);
      only 5% (4 of 82) of pvl(-) MSSA isolates were USA300. Patients with
      osteomyelitis caused by pvl isolates had significantly higher mean values for
      erythrocyte sedimentation rate at admission (P = 0.005) and erythrocyte
      sedimentation rate maximum value (P = 0.002), maximum C-reactive protein (P =
      0.04), and absolute neutrophil count at presentation (P = 0.04) compared with
      patients whose isolates were pvl(-). CONCLUSIONS: USA300 accounted for a growing
      proportion of CA-MSSA isolates among children and was associated with increased
      numbers of invasive CA-MSSA infections at TCH, especially osteomyelitis.
      Associations were found in CA-MSSA osteomyelitis between pvl and increased
      concentrations of systemic inflammatory markers in patients.

PMID- 18043450
TI  - Daptomycin therapy for invasive Gram-positive bacterial infections in children.
AB  - BACKGROUND: Clinical improvement is often delayed among children with invasive
      infections caused by multidrug resistant Gram-positive bacteria such as
      methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
      enterococci (VRE) despite use of standard antimicrobial therapy. Daptomycin, a
      bactericidal lipopeptide antibiotic, may prove useful for treatment of these
      infections in children, but clinical experience is lacking. METHODS:
      Retrospective review of medical records of hospitalized children who received
      daptomycin for treatment of invasive Gram-positive bacterial infections at
      Children's Medical Center Dallas from December 2003 to March 2007. Bacterial
      isolates were tested for susceptibility to daptomycin and characterized by pulsed
      field gel electrophoresis and polymerase chain reaction for staphylococcal
      cassette chromosome mec A. RESULTS: Sixteen children (10 male; median age, 6.5
      years) received daptomycin. Fifteen (94%) children had invasive staphylococcal
      disease (14, MRSA, of which 13 were community-associated; 1, methicillin
      susceptible S. aureus), and 1 had urinary tract infection caused by VRE. Twelve
      children with disseminated staphylococcal disease had bacteremia for 2-10 days
      despite therapy with 2 or more of the following: vancomycin, clindamycin,
      rifampin, aminoglycoside, or linezolid. The addition of daptomycin resulted in
      bacteriologic cure in 6 of 7 evaluable patients with persistent bacteremia. No
      adverse events were attributed to daptomycin. Overall, 14 patients improved and
      were discharged home, and 2 died of complications of their underlying medical
      conditions. CONCLUSIONS: The majority of patients demonstrated clinical
      improvement after addition of daptomycin to conventional antimicrobial therapy.
      Further studies are needed to assess the pharmacokinetics, pharmacodynamics,
      safety, and effectiveness of daptomycin in infants and children.

PMID- 18043451
TI  - Mixed bacterial-viral infections in septic children with leukemia.
AB  - BACKGROUND: Febrile infections in children with leukemia are common. The
      occurrence of possible mixed bacterial-viral infections is unknown. METHODS: We
      searched for viruses in leukemic children with blood culture-positive bacterial
      infections. The prospective multicenter survey included 156 febrile episodes in
      51 children with acute leukemia. The mean follow-up time was 1.5 years per
      patient (27,743 patient-days at risk). Sixteen viruses were searched for from
      nasal swab and stool samples using virus culture, virus antigen detection, and
      polymerase chain reaction tests. RESULTS: Bacterial blood cultures were positive
      in 19 (11%) febrile episodes among 17 children. In half of the septic episodes
      (11 of 19), a virus was also found. Rhinovirus and respiratory syncytial virus
      were the most common viruses detected. CONCLUSIONS: Our findings suggest that
      invasive bacterial infections are commonly associated with viral infections in
      children with leukemia.

PMID- 18043453
TI  - Failure of chemoprophylaxis with standard antituberculosis agents in child
      contacts of multidrug-resistant tuberculosis cases.
AB  - BACKGROUND: There is little published information on optimal chemoprophylaxis for
      children with multidrug-resistant tuberculosis (MDR-TB) contacts. Current
      guidelines of World Health Organization suggest that isoniazid (INH), the
      standard first-line chemoprophylaxis, be used for those exposed to MDR-TB.
      METHODS: This is a retrospective review of medical records of 5 children residing
      in the Western Cape Province, South Africa, who developed MDR-TB while receiving
      conventional chemoprophylaxis with either INH or a combination of INH, rifampin,
      and pyrazinamide. RESULTS: Adult MDR-TB source cases were identified for all
      children and resistance patterns of patient and source case isolates matched in
      all cases. The median age of the patients was 0.4 years. One patient participated
      in a trial of INH chemoprophylaxis for HIV-infected children. Four HIV-uninfected
      infants presented with TB-related symptoms several months after being given
      chemoprophylaxis because of a known source case. Stigmata of TB were cough >3
      weeks in 4, weight loss or a history of failing to thrive in 3, fever in 2
      infants, and reported night sweats in 1. Chest radiographs at diagnosis revealed
      lymphadenopathy, lobar opacification, and airway narrowing. All patients were
      treated for varying time periods at a TB referral institution in the Western
      Cape. CONCLUSIONS: Standard, first-line anti-TB agents were inadequate to prevent
      MDR-TB in children exposed to MDR-TB contacts. Second-line chemoprophylaxis,
      reflecting the susceptibility profile of the source case's isolate, with at least
      2 drugs with activity against the drug-resistant isolate for 6-12 months should
      be considered.

PMID- 18043452
TI  - Progress in measles and rubella elimination in Iran.
AB  - BACKGROUND: Measles is a leading cause of death worldwide because of vaccine
      preventable diseases. Prevention and control of measles and rubella is a high
      priority for the Islamic Republic of Iran. In 2002, the Ministry of Health and
      Medical Education in Iran developed a comprehensive strategy to eliminate measles
      and rubella. This strategy included recommendations for a mass immunization
      campaign for all persons between the ages of 5-25 years with measles-rubella (MR)
      vaccine. This report reviews the results of this campaign and progress in the
      elimination of measles and rubella in Iran. METHODS: Measles vaccination
      coverage, supplemental immunization activities, surveillance data, and results
      from a nationwide serosurvey were reviewed. RESULTS: Between 1980 and 2005,
      vaccination coverage ranged from 38%-99% with sustained high coverage (> or =94
      99%) for the past decade. Despite high coverage with the first dose of measles
      vaccine (MCV1) and the introduction of a second dose of measles in 1984, case
      counts remained high between 1980 and 2005 with a median case count of 4414. In
      December 2003, a nationwide immunization campaign was conducted targeting
      33,579,082 people between the ages of 5 and 25 years with a combined measles and
      rubella vaccine; 98% of the target population was vaccinated. A postcampaign
      serosurvey conducted in 2004 revealed >97.4% of the population aged between 5 and
      40 years had immunity to measles and rubella. Case-based surveillance for measles
      identified 3 children with laboratory confirmed disease in 2004, 35 in 2005, and
      42 children in 2006. Most confirmed disease occurred in immigrant communities or
      communities with migrant populations from neighboring counties with ongoing
      measles outbreaks. Surveillance for rubella was established after the campaign
      and identified 37 patients with confirmed disease in the follow-up period.
      CONCLUSIONS: Implementation of a comprehensive strategy for measles elimination
      in Iran has remarkably reduced the incidence of measles and rubella to <1 case
      per 1,000,000. Sporadic transmission continues to occur, particularly in areas
      with immigrant and nomadic populations.

PMID- 18043454
TI  - Hepatitis E.

PMID- 18043455
TI  - New combination vaccines: integration into pediatric practice.

PMID- 18043456
TI  - Bacterial characteristics as predictors of posttherapy recurrent bacteriuria
      among children with acute uncomplicated cystitis caused by Escherichia coli.
AB  - Multiple characteristics of pretherapy Escherichia coli urine isolates from 39
      children with acute, uncomplicated cystitis (including specific virulence genes
      and phylogenetic groups) identified an increased risk for recurrent bacteriuria
      after 3-day (but not 10-day) therapy with amoxicillin-clavulanate. Rapid testing
      conceivably could facilitate rational selection of treatment duration for
      pediatric cystitis. Certain traits might represent good targets for preventive
      interventions.

PMID- 18043457
TI  - The gastrointestinal tract serves as the reservoir for Gram-negative pathogens in
      very low birth weight infants.
AB  - We report a pilot study testing the hypothesis that Gram-negative bacilli
      colonizing the gastrointestinal tracts of infants with birth weights <1500 g are
      the source of subsequent bloodstream infections. Ninety-five percent (18 of 19)
      of paired bloodstream infection or antecedent rectal cultures were genotypically
      concordant. The gastrointestinal tract is the reservoir for most cases of Gram
      negative sepsis in this population.

PMID- 18043458
TI  - Factors influencing the decision to test young infants for herpes simplex virus
      infection.
AB  - In a nested case-control study of 478 infants < or =90 days of age, one-third of
      infants undergoing cerebrospinal fluid herpes simplex virus (HSV) testing by
      polymerase chain reaction were >28 days of age. Recognized factors, such as mode
      of delivery, were not associated with HSV testing. The factors currently used by
      physicians in the decision to order this test do not best reflect the likelihood
      of HSV infection.

PMID- 18043459
TI  - Acute rheumatic fever in American Samoa.
AB  - Acute rheumatic fever is common among Samoans in Hawaii. During 2 visits to
      evaluate the magnitude of rheumatic fever problem among Samoans in American
      Samoa, we identified 148 patients with rheumatic fever on penicillin prophylaxis.
      Retrospective chart reviews were done showing possible delays in diagnosis of
      acute rheumatic fever.

PMID- 18043460
TI  - Mortality and neurodevelopmental outcome after Staphylococcus aureus bacteremia
      in infants.
AB  - We compared outcomes in infants with methicillin-resistant and methicillin
      sensitive Staphylococcus aureus bacteremia. Infants with methicillin-resistant S.
      aureus infection had a longer median duration of bacteremia (4.5 versus 1 day, P
      = 0.01), but no difference in length of hospital stay, mortality, or
      neurodevelopmental impairment.

PMID- 18043461
TI  - Methicillin-resistant Staphylococcus aureus as a cause of extensive
      retropharyngeal abscess in two infants.
AB  - We report 2 cases of extensive methicillin-resistant Staphylococcus aureus (MRSA)
      retropharyngeal abscesses in young infants. In 1 case, the abscess was associated
      with a reactive thrombosis of the jugular vein. Based on the existing literature
      and the rapid emergence of MRSA skin and soft tissue infections, it is possible
      that similar severe infections will occur with increasing frequency in young
      infants.

PMID- 18043462
TI  - Pustular rash in Kawasaki syndrome.
AB  - The skin rash of Kawasaki syndrome is usually erythematous. A 23-month-old Costa
      Rican boy was admitted with a clinical picture compatible with Kawasaki syndrome,
      except for his skin lesions. He had diffuse, confluent, multiple sterile whitish
      pustular lesions on his chest, abdomen, neck, genitals, and thighs.

PMID- 18043463
TI  - Diagnosis and treatment of cutaneous zygomycosis.
AB  - Cutaneous zygomycosis is a rare but severe fungal infection with high risk of
      dissemination. Early recognition, deep surgical biopsy for diagnosis, aggressive
      treatment with repeated surgical debridement, and targeted pharmacotherapy are
      essential and can prevent dissemination and fatal outcome. We present case
      reports of 2 patients.

PMID- 18043464
TI  - Absidia corymbifera in a patient with chronic granulomatous disease.

PMID- 18043466
TI  - Initial antiretroviral drugs.

PMID- 18043467
TI  - Drug interactions with herbal medicines.
AB  - The use of herbal medicines (HM) is on the rise among the global population.
      Although the safety profile of many herbal medicines is promising, accumulated
      data show evidence of significant interactions with medications, which can place
      individual patients at great risk. A range of electronic databases have been
      reviewed for articles published in this field: Medline, Allied and Complementary
      Medicine Database, HealthSTAR, AMBASE, CINHAL, Cochrane Library, as well as
      Internet documents and manually searched references in medical journals. In this
      review, we examined the literature from 1966 to 2006 and focused on the
      importance of the risk of drug interactions and potential side effects when HM
      are involved. We discuss these in light of the documented findings. A review of
      the problematic issues is given and recommendations are made in order to
      encourage the setting up of clinical trials on HM and herb-drug interactions.

PMID- 18043468
TI  - Clinically important drug interactions potentially involving mechanism-based
      inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring.
AB  - Cytochrome P450 (CYP) 3A4 is the most abundant enzyme of CYPs in the liver and
      gut that metabolizes approximately 50% currently available drugs. A number of
      important drugs have been identified as substrates, inducers, and/or inhibitors
      of CYP3A4. The substrates of CYP3A4 considerably overlap with those of P
      glycoprotein. Both CYP3A4 and P-glycoprotein are subject to inhibition and
      induction by a number of factors. Mechanism-based inhibition of CYP3A4 is
      characterized by NADPH-, time-, and concentration-dependent enzyme inactivation
      occurring when some xenobiotics or drugs are converted by CYPs to reactive
      metabolites. Such an inhibition of CYP3A4 is caused by chemical modification of
      the heme, the protein, or both as a result of covalent binding of modified heme
      to the protein. To date, the identified clinically important mechanism-based
      CYP3A4 inhibitors mainly include macrolide antibiotics (eg, clarithromycin and
      erythromycin), anti-HIV agents (eg, ritonavir and delavirdine), antidepressants
      (eg, fluoxetine and fluvoxamine), calcium channel blockers (eg, verapamil and
      diltiazem), steroids and their modulators (eg, gestodene and mifepristone), and
      several herbal and dietary components. The inactivation of CYP3A4 by drugs often
      causes unfavorable and long-lasting drug-drug interactions and probably fatal
      toxicity, depending on many factors associated with the enzyme, drugs, and the
      patients. Clinicians are encouraged to have a sound knowledge of drug-induced,
      mechanism-based CYP3A4 inhibition; take proper cautions, and perform close
      monitoring for possible drug interactions when using drugs that are mechanism
      based CYP3A4 inhibitors. To minimize drug-drug interactions involving mechanism
      based CYP3A4 inhibition, it is necessary to choose safe drug combination
      regimens, adjust drug dosages appropriately, and conduct therapeutic drug
      monitoring for drugs with narrow therapeutic indices.

PMID- 18043469
TI  - Biological matrices for the evaluation of in utero exposure to drugs of abuse.
AB  - In recent years, the evaluation of in utero exposure to drugs of abuse has been
      achieved by testing biological matrices coming from the fetus or newborn (eg,
      meconium, fetal hair, cord blood, neonatal urine), the pregnant or nursing mother
      (eg, hair, blood, oral fluid, sweat, urine, breast milk), or from both the fetus
      and the mother (placenta, amniotic fluid). Overall, these matrices have the
      advantage of noninvasive collection (with the exception of amniotic fluid) and
      early detection of exposure from different gestational periods. Matrices such as
      amniotic fluid, meconium, fetal hair, and maternal hair provide a long historical
      record of prenatal exposure to certain drugs and can account for different
      periods of gestation: amniotic fluid from the early pregnancy, meconium for the
      second and third trimester of gestation, fetal hair for the third, and finally
      maternal hair (when long enough) for the whole pregnancy. Placenta may reveal the
      passage of a substance from the mother to the fetus. Cord blood and neonatal
      urine are useful for determining acute exposure to drugs of abuse in the period
      immediately previous to delivery. Drug detection in maternal blood, oral fluid,
      and sweat accounts only for acute consumption that occurred in the hours previous
      to collection and gives poor information concerning fetal exposure. Different
      immunoassays were used as screening methods for drug testing in the above
      reported matrices or as unique analytical investigation tools when
      chromatographic techniques coupled to mass spectrometry were not commonly
      available. However, in the last decade, both liquid and gas chromatography-mass
      spectrometric methodologies have been routinely applied after appropriate
      extraction of drugs and their metabolites from these biological matrices.

PMID- 18043470
TI  - Effect of diabetes mellitus on mycophenolate sodium pharmacokinetics and inosine
      monophosphate dehydrogenase activity in stable kidney transplant recipients.
AB  - Effect of diabetes mellitus on mycophenolic acid (MPA) pharmacokinetics and
      catalytic activity of inosine monophosphate dehydrogenase (IMPDH) was
      investigated in maintenance kidney transplant recipients. Demographically matched
      diabetic (n=9) and nondiabetic (n=9) patients were included in a 12-hour open
      label, steady-state study after oral administration of enteric-coated
      mycophenolate sodium. Concentrations of total MPA and free MPA, MPA-glucuronide,
      and acyl-MPA-glucuronide were measured and oral acetaminophen absorption was used
      as a marker for gastric-emptying rate. Median (range) of MPA area under the
      curve(0-12) was 36.7 (range, 16.4-116.4) mg*h/L in diabetic and 48.2 (range, 34.9
      80.1) mg*h/L in nondiabetic patients (P=0.49). All other primary pharmacokinetic
      parameters, including time to maximum concentration, for total or unbound MPA as
      well as MPA metabolites were comparable. In contrast, IMPDH activity was 17.5+/
      2.8 versus 46.6+/-2.5 nmol XMP/h/microg protein in diabetics and nondiabetics,
      respectively (P<0.0001) and was significantly lower in the diabetics irrespective
      of concomitant therapy with cyclosporine or tacrolimus. This study demonstrated
      that diabetes does not alter MPA pharmacokinetics when administered as enteric
      coated mycophenolate sodium; however, IMPDH activity appeared to be significantly
      lower in patients with diabetes independent of the unbound or total
      concentrations of MPA. Further investigations are warranted to investigate the
      regulation of IMPDH enzyme in patients with diabetes.

PMID- 18043471
TI  - Crossreactivity of isolated everolimus metabolites with the Innofluor Certican
      immunoassay for therapeutic drug monitoring of everolimus.
AB  - Everolimus is an immunosuppressant used as rejection prophylaxis in patients
      undergoing transplants. It requires blood concentration-guided dosing and is
      extensively metabolized. It was the goal to assess the crossreactivity of the
      major everolimus metabolites in the blood of patients undergoing kidney graft
      with the Innofluor Certican Assay (Seradyn, Inc., Indianapolis, IN), a clinical
      assay used to quantify the concentrations of everolimus in patients' blood
      samples. The three main hydroxy metabolites of everolimus (46-, 24-, and 25
      hydroxy everolimus) and all other minor hydroxylated and demethylated metabolites
      were generated using pooled human liver microsomes and purified using
      semipreparative high-performance liquid chromatography with ultraviolet
      detection. Structures were confirmed using liquid chromatography-mass
      spectrometry/ion trap mass spectrometry and analysis of the fragmentation
      patterns. Blank blood samples were spiked with the isolated metabolites to
      determine the specific crossreactivity with the immunoassay. Crossreactivity
      testing with the immunoassay showed 1% or less for 46-hydroxy and 24-hydroxy
      everolimus and 6% or less crossreactivity for 25-hydroxy everolimus at
      therapeutically relevant concentrations. Crossreactivity testing of the minor
      metabolites showed crossreactivities of 16.3% for 45-hydroxy, 33.0% for 12
      hydroxy, 18.3% for 11-hydroxy, 15.3% for 14-hydroxy, 38.7% for OH-piperidine I,
      46.3% for OH-piperidine II, 43% for 39-O-desmethyl, 142% for 27-O-desmethyl, and
      68% for 40-O-desethylhydroxy everolimus (sirolimus).

PMID- 18043472
TI  - Achievement of target cyclosporine concentrations as a predictor of severe acute
      graft versus host disease in children undergoing hematopoietic stem cell
      transplantation and receiving cyclosporine and methotrexate prophylaxis.
AB  - This study evaluates our institution's target trough cyclosporine (CSA)
      concentrations as predictors of severe acute graft versus host disease (aGvHD) in
      children receiving either matched related or unrelated hematopoietic stem cell
      transplantation (HSCT). The outcomes of 87 consecutive children who underwent
      allogeneic HSCT and received CSA and methotrexate as prophylaxis against aGvHD
      between October 1, 1999 and September 30, 2002 were retrospectively evaluated.
      The proportion of time that each patient maintained a whole blood CSA
      concentration within or above the initial target range (105-155 ng/mL or 155-210
      ng/mL) was calculated for each of the following time periods: in each week after
      HSCT from day 0 to +28; in the week preceding engraftment; and in the week
      preceding the onset of aGvHD. Patients were prospectively evaluated twice weekly
      for the presence and severity of aGvHD by senior attending physicians. The
      relationship between potential predictors and the development of severe aGvHD was
      examined using univariate logistic regression. The main variables of interest
      were the proportion of time that therapeutic or supratherapeutic CSA
      concentrations were maintained; median CSA concentrations; the number of
      methotrexate doses received; and the use of folinic acid rescue. Mean follow-up
      time was 3.0+/-1.9 years among children who survived beyond day +100. Three
      variables were significantly associated with the development of severe aGvHD on
      univariate analysis: initial CSA target concentration [odds ratio (OR), 0.24;
      P=0.03], proportion of time the target CSA concentration was achieved during the
      second week after transplant (OR, 0.16; P=0.02), and proportion of time the
      target CSA concentration was achieved during the week before engraftment (OR,
      0.22; P=0.0489). Multivariable analysis demonstrated an inverse relationship
      between the median CSA concentration during the week before engraftment and the
      development of severe aGvHD (OR, 0.99; P=0.045). These results suggest that
      achievement of our CSA target concentrations is important to aGvHD outcomes.

PMID- 18043474
TI  - Measurement of duloxetine in blood using high-performance liquid chromatography
      with spectrophotometric detection and column switching.
AB  - A method using high-performance liquid chromatography (HPLC) with column
      switching and ultraviolet (UV) spectroscopy was developed for the determination
      of duloxetine in human plasma. After centrifugation and addition of venlafaxine
      as internal standard, plasma samples were injected into the HPLC system and
      precleaned on a column (10 x 4.0 mm) filled with cyanopropyl (CN)-modified silica
      of 20 microm particle size, with use of 8% (vol/vol) acetonitrile in deionized
      water as eluent. Duloxetine was eluted and separated on a LiChrospher 100 CN (5
      microm particle size; column size, 250 x 4.6 mm I.D.) using acetonitrile-water
      potassium dihydrogenphosphate trihydrate buffer (pH, 6.4; 50:50 vol/vol) and
      detected at 218 nm. Duloxetine could be analyzed within 30 minutes. The limit of
      quantification was 5 ng/mL. At duloxetine concentrations up to 138 ng/mL that
      resulted from therapeutic doses of 30 to 120 mg per day, the interassay
      reproducibility of quality control samples was better than 12%. The method was
      found to be robust and stable. With the exception of chlorprothixene and
      desmethylclomipramine, other drugs that may be used as comedication were not
      found to exhibit retention times similar to duloxetine. In serum samples from 37
      patients treated with 30 to 120 mg per day for at least 7 days, the mean steady
      state serum concentration of duloxetine was 40 ng/mL, the median was 37 ng/mL,
      and the 25th and 75th percentiles were 22 and 55 ng/mL, respectively. At 60, 90,
      and 120 mg/day, the mean +/- SD serum concentrations were 33+/-22.0, 43+/-22.2,
      and 48+/-17.0 ng/mL, respectively. There was a statistically significant
      correlation (P<0.05, r2=0.26) between prescribed daily doses and serum
      concentrations of duloxetine. In patients without or with comedication with other
      drugs, such as inhibitors of cytochrome P450 2D6 (eg, metoprolol or propranolol),
      serum concentrations of duloxetine were not significantly different. HPLC with
      column switching and ultraviolet detection as described here is suitable for
      pharmacokinetic studies and therapeutic drug monitoring of duloxetine.

PMID- 18043473
TI  - Therapeutic drug monitoring of escitalopram in an outpatient setting.
AB  - The main objectives of this study were to outline the inter- and intraindividual
      and overall pharmacokinetic variability of S-citalopram, S-desmethylcitalopram,
      and S-didesmethylcitalopram in serum by means of therapeutic drug monitoring; and
      to investigate potential correlations between the serum concentration and
      simultaneously collected clinical data. The study was conducted on outpatients in
      Sweden in 2002 to 2005. Included in the pharmacokinetic evaluation were 155
      patients (68% women and 32% men) aged 17 to 95 years (average, 51 years). One
      serum sample per patient, taken as a trough value in steady state, was assessed.
      For the inter- and intraindividual variation calculation, 16 patients were
      included with two eligible samples each. The median daily dose was 20 mg/day
      (range, 5-40 mg). Extensive overall serum concentration variability was seen for
      all dose levels. The interindividual coefficient of variation for dose-normalized
      concentrations was 71% for S-citalopram, 36% for S-desmethylcitalopram, and 50%
      for S-didesmethylcitalopram. The intraindividual variations over time for the
      same parameters were approximately 30%, except for the ratio S
      desmethylcitalopram/S-citalopram, which was 23%. The median S-desmethylcitalopram
      level was approximately 60% of the parent substance and the S
      didesmethylcitalopram level approximately 9%. Higher age was correlated with
      higher serum concentrations, but no gender-related concentration differences were
      found. A majority (76%) of the patients took one or more drugs in addition to
      escitalopram, but concomitant medication did not seem to interact with
      escitalopram. However, women taking oral contraceptives showed a lower metabolic
      ratio compared with age-matched women. As a result of the wide range of the ratio
      in this population, these findings are not considered of clinical relevance.

PMID- 18043475
TI  - Simultaneous high-performance liquid chromatographic determination of olanzapine
      and lamotrigine in plasma of bipolar patients.
AB  - An original method based on the use of high-performance liquid chromatography
      with both coulometric and diode array detection has been developed for the
      therapeutic drug monitoring of patients with bipolar disorders being treated with
      olanzapine and lamotrigine. Chromatographic separation was achieved on a reversed
      phase C8 column (150 x 4.6 mm internal diameter, 5 microm) using a mobile phase
      composed of methanol (27%) and a 50.0 mmol/L, pH 3.5 phosphate buffer (73%). For
      the analysis of olanzapine and its main metabolite, N-desmethylolanzapine, a
      coulometric detector was used, with electrode 1 set at -200 mV and electrode 2 at
      +500 mV. Lamotrigine was determined using a diode array detection at 220 nm. The
      two detectors were connected in series. For the analysis of biological samples, a
      clean-up procedure was implemented by means of solid-phase extraction using
      phenyl cartridges and eluting the analytes with methanol; only a small volume of
      plasma (150 microL) was needed to analyze both olanzapine and lamotrigine. Linear
      responses were obtained between 0.1 and 50.0 ng mL(-1) for olanzapine, 0.1 and
      25.0 ng mL(-1) for N-desmethylolanzapine, and between 0.25 and 10.0 microg mL(-1)
      for lamotrigine. The extraction yield values were always higher than 90% for all
      the analytes, with precision (expressed as relative standard deviation values)
      lower than 3.4%. The method was applied successfully to some human plasma samples
      drawn from bipolar patients undergoing combined therapy with the two drugs.
      Satisfactory values for accuracy were obtained, with mean recovery higher than
      91%. Thus, the method appears suitable for the investigation of the chemical
      clinical correlations in patients receiving therapy with olanzapine and
      lamotrigine.

PMID- 18043476
TI  - Population pharmacokinetic model of carbamazepine derived from routine
      therapeutic drug monitoring data.
AB  - The aim of the present study was to develop a population pharmacokinetic model of
      carbamazepine from routine therapeutic drug monitoring data. Steady-state
      carbamazepine plasma concentrations determined by homogenous enzyme immunoassay
      technique, dosing history including cotherapy, schedule of blood sampling, and
      patients' demographic characteristics were collected retrospectively from
      patients' chart histories. A one-compartment model was fitted to the data using
      nonlinear mixed effects modeling. The influence of weight, age, gender, smoking,
      allergy, carbamazepine daily dose, and cotherapy on clearance (CL/F) was
      evaluated. Additionally, bioavailability of controlled-release relative to
      immediate-release tablets was assessed. Two hundred sixty-five patients (423
      concentrations) were used to develop a population pharmacokinetic model. The
      population estimate of CL/F from the base model was 5.14 L/h with interindividual
      variability of 50.20%. Patients' gender, age, smoking, allergy, cotherapy with
      lamotrigine and benzodiazepines had no effect on CL/F. Patient weight (WT), daily
      carbamazepine dose (DCBZ), daily dose of phenobarbitone (DPB) and valproic acid
      (VPA), when its daily dose exceeded 750 mg, significantly influenced CL/F and
      were included in the final model:[equation: see text] where VPA is 1 if dose is
      greater than 750 mg or 0 otherwise. No difference in bioavailability of
      carbamazepine between controlled- and immediate-release tablets was detected. The
      model predictions in the validation set had no bias and satisfactory precision.
      The model can be used for estimation of carbamazepine CL/F in individual patients
      in the postautoinduction phase and for selection of optimum dosing regimen in
      routine patient care.

PMID- 18043477
TI  - Serum concentrations of pregabalin in patients with epilepsy: the influence of
      dose, age, and comedication.
AB  - Pregabalin (PGB) is a new antiepileptic drug (AED) approved for adjunctive
      therapy for partial seizures with and without generalized tonic-clonic seizures
      and for the treatment of peripheral neuropathic pain in adults. PGB does not bind
      to plasma proteins and is excreted predominantly unchanged by the kidneys.
      Previous studies indicated that PGB shows no relevant interactions with other
      AEDs. The aim of this study was to investigate the influence of PGB dose, patient
      age, and comedication on the serum concentration of PGB. In total, 198 samples of
      167 (adult) inpatients who fulfilled the inclusion criteria (eg, trough
      concentration, body weight available) were investigated. A patient was considered
      twice only if the comedication had been changed. The PGB serum concentration
      (mg/L) in relation to PGB dose/body weight (mg/kg) per day (level-to-dose ratio,
      LDR, [(mg/L)/(mg/kg)=kg/L]) was calculated and compared for the most frequent
      drug combinations (n=97). Analysis of covariance (using age as covariate) carried
      out on the log-transformed data showed that comedication had a slight but
      significant (P = 0.02) effect on PGB serum concentrations. The median LDR of PGB
      was 0.29 for PGB + oxcarbazepine (n=16), 0.31 for PGB + carbamazepine (n=20),
      0.35 for PGB + levetiracetam (n=11), 0.35 for PGB + lamotrigine (n=15), and 0.39
      for PGB + valproic acid + lamotrigine (n=35). Regression analysis including all
      198 samples indicated (in accordance with analysis of covariance) that PGB
      concentrations were lower in combination with enzyme-inducing AEDs (phenytoin,
      carbamazepine, oxcarbazepine) and were age-dependent (higher in older patients).
      The PGB dose-concentration relationship was nearly linear (r=0.68, P<0.0001).
      However, patients on the same PGB dosage per body weight had rather different PGB
      trough concentrations, which could be explained only in part by age and
      comedication. The increase of PGB serum concentrations in older patients is in
      accordance with expectations for drugs that are predominantly renally excreted.
      Unexpectedly and in contrast to other studies, our data indicate that
      comedication with enzyme-inducing antiepileptic drugs (eg, carbamazepine) can
      moderately decrease PGB serum concentrations (about 20% to 30%). Further studies
      should clarify the effect of age and interactions on PGB concentrations.

PMID- 18043478
TI  - Pharmacokinetic interaction between darunavir and saquinavir in HIV-negative
      volunteers.
AB  - This was an open-label, crossover study to investigate the pharmacokinetic
      interaction between darunavir (TMC114), coadministered with low-dose ritonavir
      (darunavir/ritonavir), and the protease inhibitor saquinavir in HIV-negative
      healthy volunteers. Thirty-two volunteers were randomized into two cohorts (panel
      1 and panel 2). In two separate sessions, panel 1 received 400/100 mg
      darunavir/ritonavir twice a day and 400/1000/100 mg
      darunavir/saquinavir/ritonavir twice a day; panel 2 received 1000/100 mg
      saquinavir/ritonavir twice a day and 400/1000/100 mg
      darunavir/saquinavir/ritonavir twice a day. All treatments were administered
      orally under fed conditions for 13 days with an additional single morning dose on
      day 14. Treatment sessions were separated by a washout period of at least 14
      days. Twenty-six volunteers completed the study (n=14, panel 1; n=12, panel 2),
      whereas six discontinued as a result of adverse events. Coadministration of
      saquinavir with darunavir/ritonavir resulted in decreases of darunavir area under
      the curve and maximum and minimum plasma concentrations of 26%, 17%, and 42%,
      respectively, compared with administration of darunavir/ritonavir alone. Relative
      to treatment with saquinavir/ritonavir alone, saquinavir exposure was not
      significantly different with the addition of darunavir. Ritonavir area under the
      curve12h increased by 34% when saquinavir was added to treatment with
      darunavir/ritonavir. The coadministration of darunavir/saquinavir/ritonavir was
      generally well tolerated. Similar findings are expected with the approved 600/100
      mg darunavir/ritonavir twice-a-day dose. The combination of saquinavir and
      darunavir/ritonavir is currently not recommended.

PMID- 18043479
TI  - Measurement of ribavirin plasma concentrations by high-performance liquid
      chromatography using a novel solid-phase extraction method in patients treated
      for chronic hepatitis C.
AB  - Ribavirin (RBV) in combination with pegylated interferon is the current standard
      treatment for chronic hepatitis C. Exposure to RBV seems crucial for achieving
      the best virologic response. However, RBV may cause anemia in a dose-dependent
      manner. Therefore, monitoring RBV plasma levels could be useful for individual
      tailoring of RBV dosing. A rapid assay was developed to quantify RBV using high
      performance liquid chromatography and ultraviolet detection. Extraction of RBV
      from plasma was performed using a novel method based on ultrafiltration in one
      step that allows direct injection into the high-performance liquid chromatography
      without any prior steps of dryness or reconstitution. The method was validated
      over the range of 0.05 to 5.0 microg/mL following the EMEA Validation of
      Analytical Procedures (CPMP/ICH/281/95) recommendations. The clinical interest of
      this assay was evaluated in a subset of patients under RBV therapy. Mean RBV
      plasma concentrations at steady state were higher in responders compared with
      nonresponders (3-3.2 mug/mL versus 2.2-2.3 microg/mL).

PMID- 18043480
TI  - Orogastric and intravenous indomethacin administration to very premature neonates
      with patent ductus arteriosus: population pharmacokinetics, absolute
      bioavailability, and treatment outcome.
AB  - A population pharmacokinetic model was developed after administration of
      orogastric and/or intravenous indomethacin for the treatment of patent ductus
      arteriosus in preterm infants. Plasma indomethacin concentrations (n=227) were
      obtained from 90 preterm infants of median gestational age 27 weeks, mean
      postnatal age of 12 days, and a mean current weight (WT) of 1010 g. Infants
      received one to three courses of indomethacin (0.1 mg/kg per day for 6 days). A
      one-compartment model was fitted to the data to obtain estimates of clearance
      (CL), volume of distribution (V), absorption rate constant (Ka) and orogastric
      bioavailability (F), using NONMEM. Model robustness was assessed by bootstrapping
      with replacement (500 samples). The structural model was: CL (L/h)=0.0166 (WT /
      0.936)1.54; V (L)=0.484 (WT / 0.936)1.41; F=0.986; Ka (h(-1))=0.786. The
      interindividual variability for CL and V was 57.7% and 45.6%, respectively. There
      remained considerable residual unexplained variability (45.4%). Mean (range)
      conditional estimates from individual infants for CL, V, and elimination half
      life were 18.9 (4.7-45.5) mL/h/kg, 509 (191-1120) mL/kg, and 20.0 (12.0-37.3)
      hours, respectively. Complete ductus closure occurred in 67% of patients. Infants
      of lower gestational age or birth weight had less chance of successful ductal
      closure. There was no obvious dose-response relationship between systemic
      exposure to varying plasma indomethacin concentrations and ductus closure, which
      does not support individualized indomethacin dosing based on monitoring to a
      target plasma concentration.

PMID- 18043481
TI  - Excretion of ketoprofen and nalbuphine in human milk during treatment of maternal
      pain after delivery.
AB  - Analgesics are required to prevent and treat postpartum pain, but breast-feeding
      may be contraindicated, because data on milk transfer are very limited. The
      present study was undertaken to quantify the transfer of ketoprofen and
      nalbuphine in milk. Eighteen patients gave their informed consent to participate
      and completed the study. Following delivery, they received ketoprofen (100 mg/12
      hours) and nalbuphine (0.2 mg/kg/4 hours) as an intravenous bolus over 2 to 3
      days for postpartum pain. Milk samples were collected during the 12 hours between
      the third and fourth ketoprofen administrations. Ketoprofen and nalbuphine
      concentrations were determined with high-performance liquid chromatography. The
      mean and maximum ketoprofen milk concentrations were 57+/-37 and 91+/-51 ng/mL,
      respectively. Assuming a milk volume of 150 mL/kg/day, the mean and maximum doses
      that a breast-fed neonate would ingest during one day are 8.5+/-5.5 and 13.6+/
      7.6 microg/kg/day, respectively, and the relative infant dose is 0.31+/-0.17% of
      the weight-adjusted maternal daily dose. The mean and maximum nalbuphine milk
      concentrations were 42+/-26 and 61+/-26 ng/mL, respectively. Assuming a milk
      volume of 150 mL/kg/day, the mean and maximum doses that a breast-fed neonate
      would ingest during one day is 7.0+/-3.2 and 9.0+/-3.8 microg/kg/day, and the
      relative infant dose is 0.59+/-0.27% of the weight-adjusted maternal daily dose.
      Therefore, breast-feeding is permissible when ketoprofen and/or nalbuphine are
      administered to the mother to treat postpartum pain.

PMID- 18043482
TI  - The association between acetaminophen concentrations in the cerebrospinal fluid
      and temperature decline in febrile infants.
AB  - The objective of this study consisting of a prospective cohort of febrile infants
      was to describe the correlation between cerebrospinal fluid (CSF) acetaminophen
      (paracetamol) concentrations and changes in body temperature in febrile infants.
      Infants, one week to one year of age, with rectal temperature >or=38.0 degrees C,
      treated with acetaminophen were studied if they underwent a lumbar puncture (LP).
      Patients received 15 mg/kg of acetaminophen 30 minutes to 4 hours before lumbar
      puncture was performed. Rectal temperature was documented before acetaminophen
      administration and at the time of lumbar puncture. Plasma and CSF acetaminophen
      levels were determined using high-pressure liquid chromatography. Thirty-one
      infants were studied. In a nonlinear regression, the relationship among
      acetaminophen concentrations in the CSF, time, and temperature differences is
      best described by a Lorentzian distribution. The model suggests that a peak
      effect on temperature is achieved at CSF concentration of 11.9 microg/mL and 182
      minutes after acetaminophen administration (P<0.001 and P<0.001, respectively
      r=0.9 adjusted r square=0.78). Temperature decrement in young febrile infants,
      treated with acetaminophen, correlates with time and acetaminophen concentrations
      in the CSF. High concentrations of acetaminophen in the CSF, exceeding a certain
      level, are not associated with greater temperature decrement.

PMID- 18043483
TI  - Validated quantitation of angiotensin II receptor antagonists (ARA-II) in human
      plasma by liquid-chromatography-tandem mass spectrometry using minimum sample
      clean-up and investigation of ion suppression.
AB  - For the quantitation of angiotensin II receptor antagonists (ARA-II) in human
      plasma, a method using liquid-chromatography (LC)-electrospray ionization tandem
      mass spectrometry (MS/MS) has been developed with respect to simple sample clean
      up and investigation of ion suppression effects. For sample preparation, protein
      precipitation using zinc sulphate and methanol showed advantages in speed,
      recovery, and reproducibility over solid-phase extraction. A triple quadrupole
      mass spectrometer (Sciex API 365) with turbo ionspray source was used for
      detection of compounds with multireaction monitoring (MRM) of two transitions per
      compound. Suppression effects caused by endogenous matrix compounds were
      investigated by post-column infusion of analytes and LC analysis of precipitates
      of blank plasma samples and could be excluded. A validation was performed for the
      ARA-II drugs (valsartan, irbesartan, losartan and its active metabolite EXP 3174,
      eprosartan, candesartan, and telmisartan). The developed method showed good intra
      and interday precision (<12% relative standard deviation) and accuracy (<11.5%
      bias) at different concentrations for all the studied compounds. The calculated
      lower limits of quantitation were between 7 and 13 ng/mL, and the compounds were
      stable during the analytical process. These rather expensive drugs against
      hypertension are prescribed with increasing numbers in Europe and the
      industrialized nations. Complications might arise from overdosage or metabolic
      disorders. However, drug monitoring is not usually performed. Because the
      therapeutic concentrations range from a few nanograms to hundreds of nanograms
      per milliliter for the different drugs, and they are not amenable to gas
      chromatography/MS analysis because of their high molecular weight and polarity,
      the LC-MS/MS method is the golden standard for therapeutic drug monitoring and
      for clinical and forensic toxicology of ARA-II drugs.

PMID- 18043484
TI  - Limited sampling strategies to estimate exposure to the green tea polyphenol,
      epigallocatechin gallate, in fasting and fed conditions.
AB  - The objective of this study was to develop an efficient sampling strategy to
      predict epigallocatechin gallate (EGCG) pharmacokinetics after green tea
      administration. Ten healthy subjects received a single 800-mg oral dose of EGCG
      administered as Polyphenon E under both fasting and fed conditions. Plasma
      samples were serially collected over 24 hours and EGCG concentrations were
      determined. A one-compartment model with a lag time for absorption best fit the
      concentration-time data. Maximum A Posteriori Bayesian (MAPB) priors were
      developed by simultaneously fitting pharmacokinetic parameters from both study
      phases. The D-optimal sampling designs were determined and Monte Carlo
      simulations were performed. The original model with the estimators was used to
      fit the simulated data with the optimized sampling schemes. Two and three optimal
      sampling strategies (OSS-2 and OSS-3, respectively) were developed. The median
      two sampling times for OSS-2 were 1.3 and 6.9 hours (fasting conditions) and 3.4
      and 8.7 hours (fed conditions). The median three sampling times for OSS-3 were
      0.7, 1.4, and 7.0 hours (fasting conditions) and 1.4, 3.6, and 8.7 hours (fed
      conditions). The predictive power of OSS-3 was greater than that of OSS-2, under
      both fasted and fed conditions, and both strategies had greater predictive
      performance under fasting conditions. The sampling schemes were accurate and
      precise in predicting EGCG oral clearance (or area under the curve with known
      doses), and hence exposure, under both fasting and fed conditions. The increased
      predictive performance for estimating pharmacokinetic parameters under fasting
      conditions appeared to be the result of a decreased variability in absorption.

PMID- 18043485
TI  - Seizures and altered mental status after lamotrigine overdose.
AB  - Lamotrigine is a commonly prescribed anticonvulsant medication. It is an
      infrequently reported agent of intentional acute ingestion to poison centers. The
      spectra of clinical effects of lamotrigine in acute overdose are not well
      established. We report a case of acute ingestion of lamotrigine and ethanol that
      resulted in coma requiring ventilatory support, paradoxic seizure activity, and
      mild rhabdomyolysis.

PMID- 18043486
TI  - The role of xanthine oxidase in thiopurine metabolism: a case report.
AB  - Azathioprine (AZA) is widely used in the treatment of autoimmune inflammatory
      diseases. AZA is normally rapidly and almost completely converted to 6
      mercaptopurine (6-MP) in the liver, which is further metabolized into a variety
      of pharmacologic active thiopurine metabolites. 6-MP is catabolized by xanthine
      oxidase (XO) to the inactive metabolite 6-thiouric acid. The authors report the
      case of a woman with chronic autoimmune pancreatitis unable to form active
      thiopurine metabolites. The 55-year-old woman presented with weight loss,
      progressive elevation of liver transaminases, and serum amylase. She was treated
      with prednisolone 30 mg/day (1 mg/kg) and AZA was increased to 75 mg/day (2.5
      mg/kg); this was later increased to 150 mg/day (5 mg/kg). Despite good patient
      compliance, the active metabolites of AZA, 6-thioguanine nucleotides (6-TGN), and
      6-methylmercaptopurine ribonucleotides (6-MMPR) could not be detected in the
      erythrocytes (RBC). Subsequently, AZA was switched to high-dose 6-MP (2.5 mg/kg)
      and the XO inhibitor allopurinol was added. After 1 week, this combination led to
      a high 6-TGN level of 616 pmol/8 x 10(8) RBC and a 6-MMPR level of 1319 pmol/8 x
      10(8) RBC. Three weeks after starting treatment, 6-TGN and 6-MMPR even reached
      toxic levels (1163 pmol/8 x 10(8) RBC and 10015 pmol/8 x 10(8) RBC, respectively)
      so that 6-MP treatment was discontinued. To elucidate this finding, 6-MP (1.7
      mg/kg) was prescribed for 3 days without allopurinol. The woman was not able to
      form active thiopurine metabolites. According to the authors, this is the first
      report of a patient unable to form detectable active thiopurine metabolites on
      AZA and 6-MP therapy despite good patient compliance. High XO activity led to an
      inability to form detectable levels of active thiopurine metabolites 6-TGN and 6
      MMPR. This finding emphasizes the important role of XO in the biotransformation
      of thiopurines.

PMID- 18043487
TI  - Need for intensive histopathologic analysis to determine lymph node metastases
      when using sentinel node biopsy in oral cancer.
AB  - OBJECTIVE: To determine the predictive value of sentinel node biopsy (SNB)
      assisted neck dissection in patients with oral squamous cell carcinoma (SCC)
      stage T1 to 2N0M0 and to determine the incidence of subclinical metastases. STUDY
      DESIGN: Prospective cohort study. METHODS: Fifty-one patients with clinically N0
      neck underwent SNB-assisted neck dissection. The localization of the sentinel
      node (SN) was determined using dynamic and planar lymphoscintigraphy and single
      photon emission computed tomography-computed tomography. Histopathologic
      examination of the harvested SN was performed using step-serial sectioning with
      hematoxylin-eosin (H&E) and immunohistochemistry on formalin-fixed, paraffin
      embedded tissue. RESULTS: A total of 181 SNs were excised with a median of 3
      (range 1-7) SNs per patient. Four percent (2 of 51) of patients with subclinical
      (occult) lymph node metastasis would have been identified using routine H&E
      staining, whereas the 18% (9 of 49) were upstaged as a result of additional
      histopathology when the H&E evaluation was negative. Overall, the incidence of
      subclinical metastases was 22% (11 of 51). CONCLUSION: In this study, SNB
      assisted neck dissection proved to be technically feasible in identifying
      subclinical metastasis, thus accurately staging the neck with a high degree of
      sensitivity in patients with oral SCC T1 to 2N0M0 when additional histopathology
      was performed. The vast majority of patients in this study would have been spared
      selective neck dissection had reliance on SNB been used and selective neck
      dissection performed only in the case of a positive SN. Future studies should
      focus on determining whether SNB alone reduces patient morbidity and whether this
      is as equally effective in the treatment of cervical nodal metastases as compared
      with selective neck dissection in patients with oral SCC.

PMID- 18043488
TI  - Effects of depression on quality of life improvement after endoscopic sinus
      surgery.
AB  - OBJECTIVES/HYPOTHESIS: To determine whether self- reported depression predicts
      lesser postoperative improvement in health-related quality of life (HRQoL) after
      endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). STUDY DESIGN:
      Prospective open cohort. METHODS: An adult (> or =18 yr) cohort of 23 patients
      with depression and 79 patients without depression undergoing ESS were followed
      for 12 +/- 2 months. Patient characteristics and computed tomography scores were
      examined preoperatively. Endoscopy scores and two HRQoL measures, the
      Rhinosinusitis Disability Index (RSDI) and Chronic Sinusitis Survey, were
      analyzed pre- and postoperatively. Univariate and multivariate analyses were used
      to evaluate outcome differences for patients with depression. RESULTS: There was
      a significantly higher prevalence of women (P = .002) and longer duration of
      follow-up (P = .004) for the depressed subgroup. Depressed patients reported
      significantly lower pre- and postoperative HRQoL scores on all RSDI subscales (P
      < .05). Without baseline adjustment, depression was not associated with
      significant differences in postoperative change for disease-specific HRQoL scores
      (P > .10) in multivariate analysis. CONCLUSIONS: Depressed patients with CRS
      present similarly but have worse pre- and postoperative HRQoL scores and
      experience similar disease-specific QoL improvements from sinus surgery compared
      with other CRS patients. Sinus surgery is not effective in alleviating the effect
      of depression on disease-specific HRQoL, and it is likely that comorbid
      depression and CRS are operating on independent disease pathways. Additional
      research and hypothesis testing using continuous, objective measures is
      warranted.

PMID- 18043489
TI  - Tonsil T cell immunity to human papillomavirus in the absence of detectable virus
      in healthy adults.
AB  - BACKGROUND: Human papillomavirus (HPV) is known to infect the epithelium of the
      upper aerodigestive tract; however, major questions regarding prevalence and
      persistence of infection, and their relation to local immune response, remain
      unanswered. OBJECTIVES: To evaluate the tonsil T cell immune response to HPV and
      compare this to the frequency of detectable virus at this site. STUDY DESIGN: A
      cross-sectional study of cancer-free adults undergoing routine tonsillectomy.
      METHODS: Mucosal immune responses to recombinant HPV16 L2E6E7 and HPV6 L2E7
      antigens were measured by tonsillar T-lymphocyte proliferation assay in 13
      subjects. HPV deoxyribonucleic acid (DNA) was assessed by PCR and reverse line
      blot hybridization in an expanded population of 44 subjects. RESULTS:
      Proliferative T-cell responses to HPV16 and HPV6 were identified in all patients.
      The presence of a CD45RO+ T cell population responsive to HPV6 L2E7 was confirmed
      in three of six subjects tested. There were no CD45RO+ responses to HPV16 L2E6E7
      and no evidence of current or latent HPV infection of the tonsil. CONCLUSIONS: T
      cell memory to human papillomavirus can be identified in tonsil tissue from an
      adult population in the absence of concurrent HPV infection. How novel HPV
      vaccines might augment this preexisting cell-mediated immunity is an essential
      area for investigation.

PMID- 18043490
TI  - Regional metastases in well-differentiated thyroid carcinoma: pattern of spread.
AB  - OBJECTIVES/HYPOTHESIS: To determine the pattern of spread of WDTC to regional
      lymph nodes, in patients who presented with clinically positive nodes. STUDY
      DESIGN: Retrospective chart review. MATERIALS AND METHODS: Between October 2001
      and December 2006, a total of 27 consecutive patients (12 males, 15 females) with
      clinical evidence of cervical metastasis of well-differentiated thyroid carcinoma
      (WDTC) underwent 28 neck dissections (ND) with a mean follow-up 33.7 months.
      Papillary carcinoma was found in 24 patients and follicular carcinoma in 3. All
      neck dissection specimens were separated during surgery into levels, and analysis
      was done with respect to the levels of the neck. Clinical and demographic
      parameters were correlated to the pathologic parameters, including number of
      pathologic nodes, size of tumor, and the patient's age, with univariate and
      multivariate analysis. RESULTS: The mean number of pathologic nodes in ND
      specimen was 6.7. The predominant site of metastasis was level VI (95%), followed
      by level III (68%), level IV (57%), and level II (54%). Metastases above the XI
      nerve were found in 7% of the patients. Level V showed 20% of nodal metastasis. A
      correlation was found between size of primary tumor and number of positive
      pathologic lymph nodes (P = .02) and an inverse correlation between the age of
      the patient and the number of pathologic nodes (P = .043). CONCLUSIONS: The high
      incidence of metastatic disease in levels II through VI supports the
      recommendation for posterolateral and anterior ND in patients with WDTC and
      clinically positive nodes. The correlation between tumor size, the age of the
      patient, and the number of positive nodes is an interesting finding that warrants
      further study.

PMID- 18043491
TI  - Patient compliance to radiation for advanced head and neck cancer at a tertiary
      care county hospital.
AB  - BACKGROUND: Combined chemotherapy and radiotherapy are routinely used to treat
      advanced-stage head and neck squamous cell carcinoma (HNSCC). Patient compliance
      is often difficult given increased toxicities. Medically underserved or uninsured
      patients may lack the necessary support to complete such treatment. OBJECTIVE: To
      evaluate compliance to radiation therapy for patients with advanced stage HNSCC
      at an urban tertiary-care county hospital. STUDY DESIGN: Retrospective review.
      METHODS: Data were extracted from the charts of 136 consecutive patients who had
      been advised to undergo chemoradiotherapy for newly diagnosed HNSCC from 2004 to
      2006. Demographic and tumor-related information was collected, as was patient
      compliance with radiation treatment. Total dose, length of treatment, and
      theoretical "loss of loco-regional control" was calculated. Benchmark compliance
      data were obtained from select publications. RESULTS: Of 136 patients, 55 did not
      begin treatment or transferred care elsewhere, leaving 81 study patients. Twenty
      eight patients (35%) had unacceptable overall treatment courses. Forty-eight
      patients (59%) received less than the effective dose of 65 Gy after accounting
      for missed treatment days. Fifty-one patients (63%) had a greater than 10%
      calculated loss in loco-regional control. Univariate and multivariate analysis
      yielded no predictive value for gender, ethnicity, node status, stage, or primary
      site on compliance. CONCLUSION: Compared with other institutions, HNSCC patients
      in this setting are less likely to complete a prescribed therapeutic regimen.
      Patient and tumor characteristics measured in this study do not predict
      compliance. Organ preservation protocols require further evaluation in
      populations where compliance is suspect. Future research must examine
      interventions to improve compliance and assessment of its impact on survival.

PMID- 18043492
TI  - The use of dexamethasone to reduce pain after tonsillectomy in adults: a double
      blind prospective randomized trial.
AB  - OBJECTIVES/HYPOTHESIS: To determine the effectiveness of dexamethasone to reduce
      pain after tonsillectomy in adults by at least 13 mm on the visual analogue
      scale. The secondary objective was to reduce the use of narcotics by at least
      20%. STUDY DESIGN: This multicentric study is a prospective double-blind
      randomized controlled trial. METHODS: A total of 102 patients were enrolled and
      received a 4-day trial either of dexamethasone in decreasing doses or placebo.
      The patients were asked to note the level of pain on the visual analogue scale
      daily for 7 days. They also had to record their consumption of analgesic and any
      eventual side effects. RESULTS: There were no statistically or clinically
      significant differences between the two groups for the level of pain noted on the
      visual analogue scale for the first 4 and 7 days. There were no statistical
      differences for the consumption of hydromorphone between the two groups.
      CONCLUSION: We cannot recommend the use of dexamethasone on a routine basis
      following tonsillectomy in adults for the reduction of pain or narcotics
      consumption.

PMID- 18043493
TI  - Computational modeling of upper airway before and after adenotonsillectomy for
      obstructive sleep apnea.
AB  - Adenotonsillectomy, the first-line surgical treatment for obstructive sleep apnea
      (OSA) in children, is successful in only 50% of obese children. Computational
      fluid dynamics tools, which have been applied to differentiate OSA patients from
      those without OSA based on the airway flow characteristics, can be potentially
      used to identify patients likely to benefit from surgical intervention. We
      present computational modeling of the upper airway before and after
      adenotonsillectomy in an obese female adolescent with OSA. The subject underwent
      upper airway imaging on a 1.5 Tesla magnetic resonance imaging (MRI) scanner, and
      three-dimensional airway models were constructed using airway boundary
      coordinates from cross-sectional MRI scans. Our results using computational
      simulations indicate that, in an obese child, the resolution of OSA after
      adenotonsillectomy is associated with changes in flow characteristics that result
      in decreased pressure differentials across the airway walls and thus lower
      compressive forces that predispose to airway collapse. Application of such
      findings to an obese child seeking surgical treatment for OSA can potentially
      lead to selection of the surgical procedure most likely to result in OSA
      resolution. Effective intervention for OSA in this high-risk group will result in
      reduction in morbidity and the public health concerns associated with OSA.

PMID- 18043494
TI  - Combined VSV oncolytic virus and chemotherapy for squamous cell carcinoma.
AB  - OBJECTIVES: Vesicular stomatitis virus (VSV) is a negative-strand ribonucleic
      acid (RNA) virus that replicates specifically in tumor cells and has oncolytic
      effects in a variety of malignant tumors. We previously demonstrated recombinant
      VSV vectors incorporating viral fusion protein (rVSV-F) and interleukin 12 (rVSV
      IL12) to have significant antitumor effects against squamous cell carcinoma (SCC)
      in a murine model. Here we evaluate the potential to combine a potent
      chemotherapeutic agent for SCC (cisplatin) with rVSV-F and rVSV-IL12 to improve
      efficacy. STUDY DESIGN: In vitro, three SCC cell lines were tested using rVSV-F
      and rVSV-IL12 with cisplatin, monitoring viral replication and cell survival. In
      an orthotopic floor of mouth murine SCC model, intratumoral injections of virus
      combined with systemic cisplatin were tested for tumor control and animal
      survival. RESULTS: In vitro, virus and cisplatin combination demonstrated rapid
      replication and enhanced tumor cell kill. Human keratinocytes were unaffected by
      virus and cisplatin. In vivo, combined rVSV-F with cisplatin reduced tumor burden
      and improved survival (P = .2 for both), while rVSV-IL12 monotherapy had better
      tumor control (P = .06) and survival (P = .024) than combination therapy.
      CONCLUSIONS: Addition of cisplatin did not affect the ability of either virus to
      replicate in or kill murine SCC cells in vitro. In vivo, combination therapy
      enhancedrVSV-F antitumor activity, but diminished rVSV-IL12 antitumor activity.
      Combination therapy may provide useful treatment for SCC with the development of
      more efficient viral vectors in combination with different chemotherapy agents or
      immunostimulatory agents.

PMID- 18043495
TI  - Active noise reduction audiometry: a prospective analysis of a new approach to
      noise management in audiometric testing.
AB  - OBJECTIVES: To develop a new method of screening audiometry that reduces the
      adverse effects of low frequency background noise by using active noise reduction
      (ANR) headphone technology. DESIGN: Prospective testing within an anechoic
      chamber evaluated the physical properties of ANR headphones. A prospective
      clinical crossover study compared standard audiometry with ANR headphone
      audiometry. METHODS: Bose Aviation X circum-aural ANR headphones were tested for
      both active and passive attenuation properties in a hemi-anechoic chamber using a
      head and torso simulator. Thirty-seven otology clinic patients then underwent
      standard audiometry and ANR audiometry, which was performed in a 30- and/or 40-dB
      sound field. RESULTS: Objective ANR headphone attenuation levels of up to 12 dB
      were achieved at frequencies below 2,000 Hz. In standard audiometric testing, 40
      dB of narrow-band background noise decreased patient pure tone thresholds by 24
      dB at 250 Hz. The use of ANR technology provided 12 dB of additional attenuation.
      This resulted in a significant improvement in test results despite the 40 dB of
      background noise (P = <0.001). In a 30-dB sound field, standard audiometric
      thresholds were shifted down by an average of 12 dB. The use of ANR technology
      completely attenuated this effect and resulted in a significant improvement in
      results (P = <0.01). These results were identical to those obtained in a quiet
      sound booth. CONCLUSIONS: Despite a 30-dB sound field, ANR audiometry can produce
      an audiogram identical to that obtained in a double-walled sound booth. ANR
      headphone audiometry improves the sensitivity of audiometric screening for mild
      low-frequency hearing loss. This technology may have important applications for
      screening in schools, industry, and community practices.

PMID- 18043496
TI  - The effect of surface electrical stimulation on vocal fold position.
AB  - OBJECTIVES/HYPOTHESIS: Closure of the true and false vocal folds is a normal part
      of airway protection during swallowing. Individuals with reduced or delayed true
      vocal fold closure can be at risk for aspiration and may benefit from
      intervention to ameliorate the problem. Surface electrical stimulation is
      currently used during therapy for dysphagia, despite limited knowledge of its
      physiological effects. DESIGN: Prospective single effects study. METHODS: The
      immediate physiological effect of surface stimulation on true vocal fold angle
      was examined at rest in 27 healthy adults using 10 different electrode placements
      on the submental and neck regions. Fiberoptic nasolaryngoscopic recordings during
      passive inspiration were used to measure change in true vocal fold angle with
      stimulation. RESULTS: Vocal fold angles changed only to a small extent during two
      electrode placements (P < or = .05). When two sets of electrodes were placed
      vertically on the neck, the mean true vocal fold abduction was 2.4 degrees; while
      horizontal placements of electrodes in the submental region produced a mean
      adduction of 2.8 degrees (P = .03). CONCLUSIONS: Surface electrical stimulation
      to the submental and neck regions does not produce immediate true vocal fold
      adduction adequate for airway protection during swallowing, and one position may
      produce a slight increase in true vocal fold opening.

PMID- 18043497
TI  - Differential capture of serum proteins for expression profiling and biomarker
      discovery in pre- and posttreatment head and neck cancer samples.
AB  - INTRODUCTION: A long-term goal of our group is to develop proteomic-based
      approaches to the detection and use of protein biomarkers for improvement in
      diagnosis, prognosis, and tailoring of treatment for head and neck squamous cell
      cancer (HNSCC). We have previously demonstrated that protein expression profiling
      of serum can identify multiple protein biomarker events that can serve as
      molecular fingerprints for the assessment of HNSCC disease state and prognosis.
      METHODS: An automated Bruker Daltonics (Billerica, MA) ClinProt matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer was
      used. Magnetic chemical affinity beads were used to differentially capture serum
      proteins prior to MALDI-TOF analysis. The resulting spectra were analyzed using
      postprocessing software and a pattern recognition genetic algorithm (ClinProt
      2.0). An HNSCC cohort of 48 sera samples from 24 patients consisting of matched
      pretreatment and 6 to 12 month posttreatment samples was used for further
      analysis. Low-mass differentially expressed peptides were identified using MALDI
      TOF/TOF. RESULTS: In the working mass range of 1,000 to 10,000 m/z, approximately
      200 peaks were resolved for ionic bead capture approaches. For spectra generated
      from weak cation bead capture, a k-nearest neighbor genetic algorithm was able to
      correctly classify 94% normal from pretreatment HNSCC samples, 80% of
      pretreatment from posttreatment samples, and 87% of normal from posttreatment
      samples. These peptides were then analyzed by MALDI-TOF/TOF mass spectometry for
      sequence identification directly from serum processed with the same magnetic bead
      chemistry or alternatively after gel electrophoresis separation of the captured
      proteins. We were able to compare this with similar studies using surface
      enhanced laser desorption ionization (SELDI)-TOF to show this method as a valid
      tool for this process with some improvement in the identification of our groups.
      CONCLUSIONS: This initial study using new high-resolution MALDI-TOF mass
      spectrometry coupled with bead fractionation is suitable for automated protein
      profiling and has the capability to simultaneously identify potential biomarker
      proteins for HNSCC. In addition, we were able to show improvement with the MALDI
      TOF in identifying groups with HNSCC when compared with our prior data using
      SELDI-TOF. Using this MALDI-TOF technology as a discovery platform, we anticipate
      generating biomarker panels for use in more accurate prediction of prognosis and
      treatment efficacies for HNSCC.

PMID- 18043498
TI  - Will increasing folic acid in fortified grain products further reduce neural tube
      defects without causing harm?: consideration of the evidence.
AB  - To reduce neural tube defects (NTDs), the U.S. Food and Drug Administration (FDA)
      mandated that by January 1998 all enriched grain products should contain 140
      microg of folic acid (FA)/100 g of flour. Groups concerned with optimal
      prevention of NTDs had argued that the level should be 350 microg/100 g. However,
      when it appeared that the debate might delay implementation of any fortification,
      these groups petitioned the FDA to implement fortification at the originally
      proposed level of 140 microg/100 g, anticipating that the FDA might consider
      increasing the level at a later time. Mandated FA fortification (FAF) has now
      been in place in the United States for 9 y. The impact of this important public
      health intervention on NTD rates, the possible benefit to other disease
      conditions, and potential harms have been evaluated. As background for a possible
      request that the FDA consider increasing FAF, evidence bearing on the question of
      whether an increase can further reduce NTD births without causing harm is
      reviewed here. The published data indicate that it is appropriate that the FDA
      conduct or commission a balanced analysis of the evidence by scientists who will
      act on that evidence to decide this important question.

PMID- 18043499
TI  - Effect of cerebral hypothermia on cortisol and adrenocorticotropic hormone
      responses after umbilical cord occlusion in preterm fetal sheep.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is essential for adaptation to
      stress. In the present study, we examined the hypothesis that head cooling with
      mild systemic hypothermia would adversely affect fetal adrenocorticotropic
      hormone (ACTH) and cortisol responses to an asphyxial insult. Chronically
      instrumented preterm fetal sheep (104 d of gestation, term is 147 d) were
      allocated to sham occlusion (n = 7), 25 min of complete umbilical cord occlusion
      (n = 7), or occlusion and head cooling with mild systemic hypothermia (n = 7,
      mean +/- SEM esophageal temperature 37.6 +/- 0.3 degrees C vs 39.0 +/- 0.2
      degrees C; p < 0.05) from 90 min to 70 h after occlusion, followed by spontaneous
      rewarming. During umbilical cord occlusion, there was a rapid rise in ACTH and
      cortisol levels, with further increases after release of cord occlusion. ACTH
      levels returned to sham control values after 10 h in both occlusion groups. In
      contrast, plasma cortisol levels remained elevated after 48 h in both occlusion
      groups and were still significantly elevated in the hypothermia-occlusion group 2
      h after rewarming, at 72 h, compared with the normothermia-occlusion and sham
      groups. In conclusion, hypothermia does not affect the overall HPA responses to
      severe asphyxia in the preterm fetus but does prolong the cortisol response.

PMID- 18043501
TI  - Factors predicting ante- and postnatal growth.
AB  - Human growth is a continuous process. Studies defining factors influencing growth
      focus on discrete time points (e.g., birth), overlooking the conditional nature
      of the process. One thousand six hundred fifty Caucasian mothers who gave birth
      at term after an uncomplicated singleton pregnancy were studied using conditional
      analysis. Infant height, weight, and head circumference were obtained at birth
      and 6 mo of age. Data analysis, conditional upon birth size, was conducted as a
      stepped consideration of factors influencing phases of fetal and infant growth
      beginning with determinants of placental size. Placental weight was related to
      birth size. Seven percent of the variance in placental weight was explained by a
      combination of gestation at delivery, maternal size at first prenatal visit,
      paternal height (all positive), and increasing parity (negative). When centered
      on birth weight, 41% of the variance in placental weight was explained by birth
      weight, length of gestation, smoking during pregnancy (all positive), and a
      female baby (negative). Maternal and paternal stature equally influenced newborn
      and infant size. Conditional analysis reveals a series of modifiable (parity,
      length of gestation, and smoking) and nonmodifiable factors at different stages
      of the growth process.

PMID- 18043500
TI  - Diminished phagocytosis-induced cell death (PICD) in neonatal monocytes upon
      infection with Escherichia coli.
AB  - An imbalance in apoptosis or survival of immune cells plays an essential role in
      the pathophysiology of sepsis. Phagocytosis-induced cell death (PICD) is a common
      result of the pathogen-host cell interaction mediated by reactive oxygen species
      (ROS). Neonatal sepsis is frequently characterized by hyperinflammation. Cord
      blood monocytes (CBMO) are equivalent to monocytes of adults [peripheral blood
      monocytes (PBMO)], both in terms of phagocytosis and killing of Escherichia coli.
      We investigated whether CBMO are less sensitive toward PICD compared with PBMO.
      Monocytes were infected with green fluorescent protein (GFP)-labeled E. coli.
      Phagocytic activity, cell-count, Annexin V staining, hypoploid DNA content, CD95
      and CD95L expression, and caspase-8 and -9 activities were analyzed by flow
      cytometry, ROS production by chemiluminescence, and CD95L mRNA expression by
      reverse-transcriptase polymerase chain reaction. With equal phagocytic activity
      and ROS production, PBMO cell count was decreased by 82 +/- 6% versus 28 +/- 8%
      for CBMO after infection. Annexin V binding was enhanced fivefold on PBMO; 56 +/-
      15% of PBMO showed a hypodiploid DNA content compared with 9 +/- 6% of CBMO.
      Caspases CD95L and CD95L mRNA were up-regulated in PBMO. Our results indicate
      that CBMO are less sensitive toward E. coli-mediated PICD than PBMO. Modifying
      monocyte apoptosis may be a target for future interventions in sepsis.

PMID- 18043502
TI  - (TA)n UDP-glucuronosyltransferase 1A1 promoter polymorphism in Nigerian neonates.
AB  - Nigerian neonates have a high incidence of bilirubin encephalopathy. Glucose-6
      phosphate dehydrogenase (G-6-PD) deficiency is prevalent in this population.
      (TA)7 promoter polymorphism in the gene encoding the bilirubin conjugating enzyme
      UDP-glucuronosyltransferase 1A1 (UGT1A1) potentiates hyperbilirubinemia in G-6-PD
      deficient neonates. We studied (TA)n allele frequency to determine, at least in
      part, its contribution to the frequency and severity of hyperbilirubinemia. DNA
      was extracted from umbilical cord blood of sequentially born Nigerian neonates
      and the (TA)n UGT1A1 promoter sequence determined. The (TA)n allele distribution
      was compared with reported adults of varying African ancestry and Sephardic
      Jewish neonates. Among 88 Nigerian neonates, (TA)6 and (TA)7 alleles were almost
      equally distributed (0.46 and 0.43, respectively). Some individuals with (TA)5
      and (TA)8 sequences were encountered. Allele distribution was similar to that of
      the African ancestry population but differed from the Sephardic Jewish newborns,
      in whom the (TA)6/(TA)7 distribution was 0.65/0.35. Whereas 45% of Nigerian
      alleles and 50% of African ancestry alleles, respectively, included a (TA)7 or
      (TA)8 sequence, only 35% of Jewish alleles were (TA)7 (p < 0.001), and no (TA)8
      alleles were encountered. The high frequency of (TA)n promoter polymorphism,
      coupled with G-6-PD deficiency, may contribute to the pathogenesis of extreme
      neonatal hyperbilirubinemia in Nigeria.

PMID- 18043503
TI  - Effects of dietary isoflavones on proliferation and DNA integrity of myoblasts
      derived from newborn piglets.
AB  - Soy-based formulas are consumed by growing numbers of infants and used as regular
      food supplements in livestock production. Moreover, constituent dietary
      phytoestrogens may compete with endogenous estrogens and affect individual
      growth. This study aimed to investigate the in vitro effects of isoflavones in
      comparison with estrogens on the proliferation of porcine satellite cells derived
      from neonatal muscle. After 7 h of exposure in serum-free medium, 17beta
      estradiol (1 nM, 1 microM), estrone (1 microM), and daidzein (1, 100 microM)
      slightly decreased whereas 100 microM genistein substantially lowered DNA
      synthesis. Declines in DNA amount were observed with genistein (1, 100 microM)
      and daidzein (100 microM). After 26 h of exposure, 100 microM genistein reduced
      DNA synthesis, whereas it was increased by 10 microM genistein and 10 and 100
      microM daidzein. In the case of 10 microM genistein and 100 microM daidzein,
      these increases apparently resulted from the repair of damaged DNA. Genistein and
      daidzein (100 microM) reduced protein synthesis, caused a G2/M phase block, and
      decreased DNA amount in association with higher rates of cell death partially
      resulting from apoptosis. Conclusively, isoflavones at concentrations of greater
      than 1 muM act as inhibitors of porcine skeletal muscle cell proliferation.

PMID- 18043504
TI  - Abnormal motor cortex excitability in congenital stroke.
AB  - The aim of the present study was to investigate corticospinal and intracortical
      excitability in patients with congenital stroke. In adults, stroke sequelae
      reduce corticospinal excitability, as indicated by an elevated threshold for
      motor evoked potentials (MEP), and increase intracortical excitability, as
      indicated by reduced intracortical inhibition. Ten patients with pre- or
      perinatally acquired, unilateral cortico-subcortical infarctions in the middle
      cerebral artery territory were studied with single pulse transcranial magnetic
      stimulation (TMS) to measure motor threshold (MT) and with paired pulse TMS to
      study short interval intracortical inhibition (SICI) and intracortical
      facilitation (ICF). Eight healthy, age-matched subjects served as controls. MT
      over the affected hemisphere of patients compared with the dominant hemisphere of
      controls was significantly elevated, reflecting reduced corticospinal
      excitability, and SICI was significantly reduced, reflecting increased
      intracortical excitability. No such differences were found for ICF. Findings in
      patients with congenital stroke were comparable with adulthood stroke. Thus,
      similar assumptions can be made: reduced corticospinal excitability is probably a
      consequence of neuronal damage. Reduced intracortical inhibition might represent
      deficient inhibitory cortical properties or might reflect a compensational
      mechanism, dispositioning for use-dependent plasticity.

PMID- 18043505
TI  - Mouse model of heterotaxy with single ventricle spectrum of cardiac anomalies.
AB  - Heterotaxy arises from a failure of the embryo to establish normal left-right
      asymmetry and is known to affect 3% of infants with congenital heart disease. A
      recessive mutation causing heterotaxy was recovered in a mouse mutagenesis screen
      focused on congenital heart defects. Homozygote mutants exhibit abnormal situs in
      the thoracic and abdominal cavities. Dextrocardia, levocardia, or mesocardia was
      seen together with right pulmonary isomerism and complex structural heart defects
      in the single ventricle spectrum. A dominant chamber of left ventricular
      morphology positioned on the left or right is seen together with transposition of
      the great arteries. Right atrial isomerism with or without total anomalous
      pulmonary venous connection was observed in half of the mutants. Because ciliary
      motion at the embryonic node is required for the specification of laterality, we
      examined the tracheal epithelia of newborn mice as a proxy for the nodal cilia.
      However, videomicroscopy showed no defect in ciliary motion. Genome scanning
      using polymorphic microsatellite markers mapped the mutation to a 3.3 Mb interval
      on mouse chromosome 7. None of the genes previously described for familial
      heterotaxy were found in this interval, indicating a novel mutation in this mouse
      model of heterotaxy.

PMID- 18043506
TI  - Role of matrix metalloproteinase-2 in newborn mouse lungs under hypoxic
      conditions.
AB  - Hypoxia impairs normal neonatal pulmonary artery remodeling and alveolar
      development. Matrix metalloproteinase-2 (MMP-2), which regulates collagen
      breakdown, is important during development. Our objective was to test the
      hypothesis that hypoxia attenuates the normal postnatal increase in MMP-2 and
      evaluate alveolar development and pulmonary arterial remodeling in Mmp2 mice.
      C57BL/6 wild-type (WT), Mmp2, Mmp2, and MMP-inhibited (with doxycycline) mice
      were exposed to hypoxia (12% O2) or air from birth to 2 wk of age. Pulmonary
      arterial remodeling, alveolar development, and vascular collagen and elastin were
      evaluated. MMP-2 was estimated by quantitative real-time polymerase chain
      reaction, enzyme-linked immunosorbent assay, immunohistochemistry, and
      zymography. We observed that 1) in WT mice, hypoxia led to thicker-walled
      pulmonary arteries and impaired alveolarization, accompanied by decreased MMP-2
      and increased tissue inhibitor of metalloproteinases-2 (TIMP-2); 2) Mmp2 mice in
      air had thicker-walled arteries, impaired alveolarization, and increased
      perivascular collagen and elastin compared with WT; 3) hypoxia further inhibited
      alveolarization but did not alter arterial thickening in Mmp2 mice. Mmp2 and MMP
      inhibited mice also had thicker-walled arteries than WT in air, but
      alveolarization was not different. We conclude that hypoxia reduces the postnatal
      MMP-2 increase in the lung, which may contribute to abnormal pulmonary arterial
      remodeling and impaired alveolarization.

PMID- 18043508
TI  - Rectal potential difference and the functional expression of CFTR in the
      gastrointestinal epithelia in cystic fibrosis mouse models.
AB  - Cystic fibrosis (CF) is an autosomal recessive disease that results from
      mutations in the CF transmembrane conductance regulator (CFTR) gene. The effect
      of interventions aimed at correcting the CF electrophysiologic phenotype has been
      primarily measured using in vitro methods in gastrointestinal and respiratory
      epithelia. A reliable in vivo assay of CFTR function would be of great value in
      the investigation of pharmacologic interventions for CF mouse models. We
      performed the in vivo rectal potential difference (RPD) assay on three different
      mouse models. We then compared the in vivo data with the results obtained using
      the in vitro Ussing chamber method. The results from the in vitro method
      correlated closely with the results acquired using the in vivo method and were
      reproducible. The data suggest that the in vivo RPD assay is a reliable assay of
      functional CFTR expression in CF mouse models.

PMID- 18043507
TI  - Acute effectors of GLUT1 glucose transporter subcellular targeting in CIT3 mouse
      mammary epithelial cells.
AB  - Lactogenic hormones cause intracellular targeting of glucose transporter 1
      (GLUT1) for transport of glucose to the site of lactose synthesis in mammary
      glands. Our aim was to study the intracellular trafficking mechanisms involved in
      GLUT1 targeting and recycling in CIT3 mouse mammary epithelial cells. Fusion
      proteins of GLUT1 and enhanced green fluorescent protein (EGFP) were expressed in
      CIT3 cells maintained in growth medium (GM), or exposed to secretion medium (SM),
      containing prolactin. Agents acting on Golgi and related subcellular compartments
      and on GLUT1 and GLUT4 targeting in muscle and fat cells were studied. Wortmannin
      and staurosporine effects on internalization of GLUT1 were not specific,
      supporting a basal constitutive GLUT1 membrane-recycling pathway between an
      intracellular pool and the cell surface in CIT3 cells, which targets most GLUT1
      to the plasma membrane in GM. Upon exposure to prolactin in SM, GLUT1 was
      specifically targeted intracellularly to a brefeldin A-sensitive compartment.
      Arrest of endosomal acidification by bafilomycin A1 disrupted this prolactin
      induced GLUT1 intracellular trafficking with central coalescence of GLUT1-EGFP
      signal, suggesting that it is via endosomal pathways. This machinery offers
      another level of regulation of lactose synthesis by altering GLUT1 targeting
      within minutes to hours.

PMID- 18043509
TI  - Mosaic pattern of sucrase isomaltase deficiency in two brothers.
AB  - The pathophysiology of mucosal changes observed in infants with chronic
      protracted diarrhea is poorly understood. We report on two brothers suffering
      from a special form of sucrase isomaltase (SI) deficiency. The children presented
      with weight loss and dyspepsia after sucrose exposition. We performed an H
      respiration test, which showed a pathologic result in the younger brother.
      Analysis of the brush border enzyme activities showed low expression of lactase
      and SI. Immunoelectron microscopy of duodenal biopsies showed an isolated SI
      deficiency in a mosaic pattern [e.g., 42% (14%) crypt enterocytes and 64% (59%)
      villus enterocytes with decreased amounts of SI on microvilli], whereas lactase
      and aminopeptidase n (ApN) were present at the apical membrane of all cells in a
      normal range. The SI mosaic pattern of these patients shows that the enterocytes
      contain low amounts of SI on the apical membrane but express normal quantities of
      other disaccharidases. These findings suggest the existence of different clonal
      expressions or specific (posttranslational) mechanisms of postGolgi
      transportation for individual brush border enzymes. It remains unresolved whether
      the mosaic distribution is part of a normal maturation process or caused by a
      lack of an overall control mechanism in the expression of brush border
      hydrolases.

PMID- 18043510
TI  - VEGF attenuates hyperoxic injury through decreased apoptosis in explanted rat
      embryonic lung.
AB  - Ambient oxygen concentration and vascular endothelial growth factor (VEGF)-A are
      vital in lung development. Since hypoxia stimulates VEGF-A production and
      hyperoxia reduces it, we hypothesized that VEGF-A down-regulation by exposure of
      airways to hyperoxia may result in abnormal lung development. An established
      model of in vitro rat lung development was used to examine the effects of
      hyperoxia on embryonic lung morphogenesis and VEGF-A expression. Under
      physiologic conditions, lung explant growth and branching is similar to that seen
      in vivo. However, in hyperoxia (50% O2) the number of terminal buds and branch
      length was significantly reduced after 4 d of culture. This effect correlated
      with a significant increase in cellular apoptosis and decrease in proliferation
      compared with culture under physiologic conditions. mRNA for Vegf164 and Vegf188
      was reduced during hyperoxia and addition of VEGF165, but not VEGF121, to
      explants grown in 50% O2 resulted in partial reversal of the decrease in lung
      branching, correlating with a decrease in cell apoptosis. Thus, hyperoxia
      suppresses VEGF-A expression and inhibits airway growth and branching. The
      ability of exogenous VEGF165 to partially reverse apoptotic effects suggests this
      may be a potential approach for the prevention of hyperoxic injury.

PMID- 18043511
TI  - Ventricle-specific metabolic differences in the newborn piglet myocardium in vivo
      and during arrested global ischemia.
AB  - Ventricular dysfunction is reported greater in the left (LV) versus right
      ventricle (RV) in infants following surgically induced ischemia. Ventricle
      specific differences in baseline metabolism may alter response to ischemia thus
      affecting postischemic functional recovery. This study identifies ventricle
      specific metabolic differences in the newborn (piglet) heart at baseline
      (working) and during ischemia (arrested). Baseline LV citrate synthase (CS) and
      hydroxyacyl-CoA dehydrogenase (HAD) activities were 15% and 18% lower (p < 0.02),
      whereas creatine kinase (CK) and phosphofructokinase (PFK) activities were 40%
      and 23% higher (p < 0.04) than the RV. Baseline LV glycogen reserves were also
      55% higher (p = 0.004). By 15 min of ischemia, LV ATP was 20% lower (p < 0.05),
      lactate was 51% higher (p = 0.001), and hydrogen ions (H) were 43% higher (p =
      0.03) compared with the RV. These differences persisted for the entire ischemic
      period (p < 0.02). After 45 min of ischemia, the LV used 58% less (p < 0.05)
      glycogen than the RV. These findings demonstrate that the enhanced glycolytic
      capacity of the newborn LV was accompanied by greater anaerobic end-product
      accumulation and lower energy levels during ischemia. This profile may offer one
      explanation for greater LV-dysfunction relative to the RV in children following
      ischemia.

PMID- 18043512
TI  - Does retrograde diastolic flow in the descending aorta signify impaired systemic
      perfusion in preterm infants?
AB  - High-volume systemic-to-pulmonary ductal shunting occurs frequently in preterm
      infants and is indicated by diastolic flow reversal in the descending aorta
      (DAo). We studied the relationship between ductal diameter, diastolic DAo
      reversal, and left ventricular output (LVO); and superior vena caval (SVC) flow
      (upper body perfusion) and DAo flow (lower body perfusion) in preterm (<31 wk)
      infants. Echocardiographic assessments were performed at 5, 12, 24, and 48 h
      postnatal age (80 infants, median gestation 28 wk, 1060 g). Incidence of ductal
      patency fell from 100% at 5 h to 72% at 48 h; incidence of pure systemic-to
      pulmonary shunting increased from 66% to 95% of infants with patent ducts. In
      infants with duct diameter greater than the median, 35-48% of infants had DAo
      flow reversal. In infants with duct diameter greater than median, DAo reversal
      was associated with 23-29% increases in LVO at 5-48 h, and 35% decreases in DAo
      flow volume at 24-48 h, but no differences in SVC flow. In conclusion, a large
      duct with left-to-right shunting is common in preterm infants. Retrograde DAo
      flow is a marker of high-volume shunt, evidenced by increased LVO. Preterm
      infants with high-volume ductal shunt may have preserved upper body perfusion but
      reduced lower body perfusion.

PMID- 18043513
TI  - Injury mechanism dictates contribution of bone marrow-derived cells to murine
      hepatic vascular regeneration.
AB  - Stem and progenitor cells derived from adult marrow have been shown to regenerate
      vascular cells in response to injury. However, it is unclear whether the type of
      injury dictates the contribution of such cells to neovascularization and which
      subpopulations of cells contribute to vascular regeneration. To address these
      questions, we determined the extent that hematopoietic stem cells (HSC)
      contributed to blood vessel formation in response to two types of liver injury,
      partial hepatectomy (PH) and toxin-induced injury. Lac-Z-labeled HSC were
      engrafted into lethally irradiated, genetically matched recipients. After 14 d,
      we identified transplanted cells engrafted within the vascular endothelium of
      toxin-damaged liver, but not in the vasculature of liver regenerated in response
      to PH. Engraftment of HSC-derived cells occurred in a gradient fashion with the
      highest activity in the severely injured areas. Although HSC-derived cells
      contributed to both microvessels and large vessels, the large caliber vessels
      trended toward higher engraftment levels. Thus, the contribution of marrow
      derived cells to hepatic neovascularization is dependent upon the type of injury
      sustained. Furthermore, following toxin-induced liver injury, engraftment rates
      trended higher in large vessels compared with capillaries, suggesting that
      remodeling of existing vessels is a predominant mechanism of repair, relative to
      the formation of new microvasculature.

PMID- 18043514
TI  - Pulse wave velocity in end-stage renal disease: influence of age and body
      dimensions.
AB  - Arterial stiffness increases with age. This process is accelerated by end-stage
      renal disease (ESRD). Pulse wave velocity (PWV) increases with arterial
      stiffness. In this study, PWV of 133 healthy individuals (6-23 y of age) and 11
      patients on dialysis was measured to establish the normal values of PWV and to
      compare them with those in ESRD. Age-matched (A-C) and height- and weight-matched
      (H/W-C) control groups were used. Thereafter, PWV was indexed to height and the
      data were reevaluated. The role of the risk factors including serum calcium,
      phosphate, parathyroid hormone (PTH), and the time on dialysis was analyzed using
      a score system. PWV correlated with age, weight, height, blood pressure, and
      heart rate. ESRD patients were smaller than A-C and older than H/W-C. PWV of
      patients with ESRD did not differ from A-C; however, it was elevated in
      comparison to H/W-C. In both healthy and ESRD patients, the PWV/height ratio was
      independent of age. PWV/height was increased in ESRD. There was a correlation
      between PWV/height and the risk factor score. Controls matched for height and
      weight or PWV/height should be used in cases of growth failure. A number of risk
      factors responsible for increased arterial stiffness are present in ESRD.

PMID- 18043515
TI  - Maternal anthropometrics in pregnancy are associated with left ventricular mass
      in infancy. The generation R study.
AB  - Pregnancy and early life factors may permanently affect left ventricular growth
      and development in the offspring. The aim of this study was to examine the
      associations of maternal anthropometrics during pregnancy with left ventricular
      mass (LVM) in infancy. This study was embedded in the Generation R Study, a
      population-based prospective cohort study from fetal life onwards. Maternal
      anthropometrics were obtained in early (gestational age <18 wk), mid-
      (gestational age 18-25 wk), and late (gestational age >25 wk) pregnancy.
      Echocardiographic follow-up measurements were performed in 791 infants aged 6 wk
      and 6 mo. We found no associations of maternal height, weight, or body mass index
      (BMI) measured in early, mid-, and late pregnancy with longitudinally measured
      left ventricular mass (LVM) from 6 wk to 6 mo. Maternal weight gain until late
      pregnancy was associated with an increased growth of LVM from 6 wk to 6 mo
      [difference 0.46 g per week for the highest tertile of weight gain compared with
      the lowest tertile (p value <0.05)]. We concluded that maternal weight gain until
      late pregnancy is associated with larger LVM at the age of 6 mo, suggesting that
      maternal health status during pregnancy may have permanent consequences for LVM
      in their children. Further studies are needed to identify the underlying causal
      mechanisms and the long-term consequences.

PMID- 18043516
TI  - Corpus callosum size in relation to motor performance in 9- to 10-year-old
      children with neonatal encephalopathy.
AB  - Magnetic resonance imaging studies have contributed to recognize the patterns of
      cerebral injury related to neonatal encephalopathy (NE). We assessed whether a
      smaller corpus callosum (CC) explained the difference in motor performance
      between school-age children with NE and controls. Frontal, middle, and posterior
      areas of the CC were measured in 61 9-10-y-old children with NE and in 47
      controls. Motor performance was determined using the Movement Assessment Battery
      for Children (M-ABC). Linear regression was used to assess whether differences in
      M-ABC between NE children and controls could be explained by CC size. The CC of
      11/30 children with NE type I according to Sarnat (NE I) and 19/36 children with
      NE type II according to Sarnat (NE II) showed generalized or focal thinning,
      compared with 8/49 controls. Children with NE II had significantly smaller middle
      and posterior parts and total areas of the CC. Children with NE scored
      significantly worse on the M-ABC than controls. The reduction in size of the
      posterior part of the CC partly explained the mean differences on the M-ABC.
      Children with NE have poorer motor skills than controls, which is partly
      explained by a smaller size of the CC.

PMID- 18043517
TI  - Brainstem amino acid neurotransmitters and ventilatory response to hypoxia in
      piglets.
AB  - The ventilatory response to hypoxia is influenced by the balance between
      inhibitory (GABA, glycine, and taurine) and excitatory (glutamate and aspartate)
      brainstem amino acid (AA) neurotransmitters. To assess the effects of AA in the
      nucleus tractus solitarius (NTS) on the ventilatory response to hypoxia at 1 and
      2 wk of age, inhibitory and excitatory AA were sampled by microdialysis in
      unanesthetized and chronically instrumented piglets. Microdialysis samples from
      the NTS area were collected at 5-min intervals and minute ventilation (VE),
      arterial blood pressure (ABP), and arterial blood gases (ABG) were measured while
      the animals were in quiet sleep. A biphasic ventilatory response to hypoxia was
      observed in wk 1 and 2, but the decrease in VE at 10 and 15 min was more marked
      in wk 1. This was associated with an increase in inhibitory AA during hypoxia in
      wk 1. Excitatory AA levels were elevated during hypoxia in wk 1 and 2. Changes in
      ABP, pH, and ABG during hypoxia were not different between weeks. These data
      suggest that the larger depression in the ventilatory response to hypoxia
      observed in younger piglets is mediated by predominance of the inhibitory AA
      neurotransmitters, GABA, glycine, and taurine, in the NTS.

PMID- 18043518
TI  - Betamethasone attenuates oxidant stress in endothelial cells from fetal lambs
      with persistent pulmonary hypertension.
AB  - We investigated the effects of betamethasone on oxidative stress and impaired
      vasodilation in a lamb model of persistent pulmonary hypertension (PPHN). We
      treated pregnant ewes following fetal ductal ligation with betamethasone or
      saline for 48 h before delivery. Response of fetal pulmonary arteries to nitric
      oxide synthase (NOS) agonist adenosine triphosphate (ATP) and nitric oxide (NO)
      donor, s-nitroso-n-acetyl-penicillamine (SNAP) was determined in tissue bath.
      Pulmonary artery endothelial cells (PAEC) from fetal lambs with ductal ligation
      or sham ligation were treated with betamethasone or its vehicle for 48 h.
      Expression of endothelial NOS (eNOS), endothelin, endothelin-B (ET-B) receptor,
      and CuZn- and Mn-superoxide dismutase (SOD) in PAEC was studied. Intracellular
      cGMP and superoxide levels and interaction of eNOS with heat shock protein 90
      (Hsp90) were determined in PAEC. Antenatal betamethasone improved the relaxation
      response of pulmonary arteries to ATP and SNAP in PPHN. PPHN was associated with
      decreases in eNOS and ET-B receptor and increase in prepro-endothelin mRNA
      levels. Betamethasone decreased prepro-endothelin mRNA and ET-1 pro-peptide
      levels and increased eNOS and MnSOD protein levels in PPHN. Betamethasone
      reversed the increased superoxide/decreased cGMP levels and restored Hsp90-eNOS
      interactions in PPHN. Betamethasone reduces oxidative stress and improves
      response of pulmonary arteries to vasodilators in lambs with PPHN.

PMID- 18043519
TI  - Child abuse and health-related quality of life in adulthood.
AB  - Past research has indicated that child abuse is related to mental and physical
      health conditions and that mental and physical health conditions are related to
      decreased health-related quality of life (HRQOL). However, little is known about
      the independent relationship between child abuse and HRQOL. For the current
      analysis, data were from the nationally representative Netherlands Mental Health
      Survey and Incidence Study. Multiple linear regression analyses tested the
      relationships between child abuse and current HRQOL (SF-36) after adjusting for
      the effects of sociodemographic variables and numerous psychiatric disorders and
      physical health conditions. Neglect, psychological abuse, physical abuse, severe
      sexual abuse, and number of types of child abuse experienced were associated with
      reduced mental HRQOL. Psychological abuse, physical abuse, and number of types of
      child abuse experienced were associated with reduced physical HRQOL. Child abuse
      is an important determinant of HRQOL. The ability to successfully reduce the
      occurrence of child abuse or provide early intervention after child abuse occurs
      may help to improve HRQOL in the general population.

PMID- 18043520
TI  - Factors linked to distress in mothers of children disclosing sexual abuse.
AB  - The aim of the present study is to investigate the variability in clinical level
      of psychological distress experienced by mothers of sexually abused children by
      exploring the role of (a) abuse-related variables (length, severity, and identity
      of perpetrator), (b) a history of childhood sexual abuse and partner violence
      experienced in the past year, and (c) mothers' coping and feelings of
      empowerment. Data were collected through self-report measures completed by 149
      French-speaking mothers of girls aged 4 to 12 years disclosing sexual abuse.
      Results revealed that more than half of the mothers reported clinical levels of
      psychological distress and experienced child sexual abuse, and 1 of 4 mothers
      experienced physical partner violence. Logistic regression analysis revealed that
      mother's sexual abuse and partner violence as well as avoidance coping and
      empowerment contributed to scores reaching clinical levels of psychological
      distress. In addition, mothers of child victims of intrafamilial sexual abuse are
      more likely to report clinical levels of distress. Results underscore the
      importance of evaluating for trauma history and taking coping strategies and
      empowerment into account in treatment interventions.

PMID- 18043521
TI  - Why dissociation and schizotypy overlap: the joint influence of fantasy
      proneness, cognitive failures, and childhood trauma.
AB  - A number of studies have noted that dissociative symptoms (e.g., feelings of
      derealization, depersonalization, memory complaints, absorption) overlap with the
      tendency to report psychotic-like experiences (i.e., schizotypy). The question
      arises as to what may account for the shared variance between dissociation and
      schizotypy. The present study investigated whether fantasy proneness, cognitive
      failures, and childhood trauma may jointly explain the dissociation-schizotypy
      link. To this end, we administered the Dissociative Experiences Scale, the
      Schizotypal Personality Scale, the Creative Experiences Questionnaire, the
      Cognitive Failures Questionnaire, and the Childhood Trauma Questionnaire to a
      sample of undergraduates (N = 185). Fantasy proneness, cognitive failures, and
      childhood trauma together explained substantial part (58%) of the dissociation
      schizotypy link. The present study succeeded in explaining a considerate part of
      the shared variance between dissociation and schizotypy.

PMID- 18043522
TI  - Personality organization, five-factor model, and mental health.
AB  - Otto Kernberg has developed a model of personality and psychological functioning
      centered on the concept of personality organization. The purpose of this study is
      to empirically examine the relationships between this model, the five-factor
      model, and mental health. The Personality Organization Diagnostic Form (Diguer et
      al., The Personality Organization Diagnostic Form-II (PODF-II), 2001), the NEO
      Five-Factor Inventory (Costa and McCrae, Revised NEO Personality Inventory (NEO
      PI-R) and NEO Five-Factor Inventory (NEO-FFI) Professional Manual. 1992a), and
      the Health-Sickness Rating Scale (Luborsky, Arch Gen Psychiatry. 1962;7:407-417)
      were used to assess these constructs. Results show that personality organization
      and personality factors are distinct but interrelated constructs and that both
      contribute in similar proportion to mental health. Results also suggest that the
      integration of personality organization and factors can provide clinicians and
      researchers with an enriched understanding of psychological functioning.

PMID- 18043523
TI  - The development and psychometric evaluation of the emotional reactivity and
      numbing scale.
AB  - Recent research has highlighted the role of hyperresponsivity and numbing of
      emotions in posttraumatic stress disorder. Preliminary research suggests that
      emotional numbing symptoms impact the development, maintenance, and treatment of
      posttraumatic stress disorder. However, research in this area has been hindered,
      in part, due to the absence of a psychometrically sound, conceptually based
      measure of emotional numbing. The present study examined the psychometric
      properties of the Emotional Reactivity and Numbing Scale in a sample of 92 trauma
      exposed men and women veterans. Results provide preliminary support for the
      internal consistency, test-retest reliability, convergent, and discriminant
      validity of the measure. Implications for future research are discussed.

PMID- 18043524
TI  - Creativity and psychopathology: higher rates of psychosis proneness and nonright
      handedness among creative artists compared to same age and gender peers.
AB  - Creative people have been found to score higher on psychopathologic scales in
      standardized tests, particularly on the scales that measure traits of
      psychoticism, and to be more likely to report an excess of nonright handedness
      compared with controls. However, results are inconsistent across surveys and
      methodologies, and the contribution of substance abuse has rarely been measured.
      In this study, 80 creative artists were compared with 80 matched noncreative
      controls on the Annett Hand Preference Questionnaire (HPQ), the Peters et al.
      Delusions Inventory, and the General Health Questionnaire. Creative artists were
      statistically more likely to admit the use of the left hand on the HPQ, with more
      widespread left hand use reported by artists involved in the creative activities
      traditionally associated with the right hemisphere (music and painting). They
      also scored higher on the Peters et al. Delusions Inventory independently from
      the level of psychopathology (measured with the General Health Questionnaire),
      from their laterality score (measured with the HPQ), and from their higher use of
      both licit and illicit drugs.

PMID- 18043525
TI  - The significance of family history in first-episode schizophrenia spectrum
      disorder.
AB  - There have been inconsistent findings regarding the significance of family
      history of schizophrenia spectrum disorders in relation to presentation and
      course of illness. There has been little research relevant to this issue from
      first-episode patients. We examined the differences in premorbid adjustment,
      symptoms, and intellectual functioning between 28 first-episode schizophrenia
      spectrum patients with a history of such illness in first degree relatives and 28
      matched patients without such a family history. The results indicate that whereas
      the 2 groups did not differ in presenting symptoms, those with a positive family
      history showed poorer intellectual functioning and less reduction in symptoms at
      2 and 3 year follow-up and greater likelihood of abnormal electroencephalogram
      findings. The findings provide evidence that presence of a positive family
      history in first-episode patients is associated with a more pernicious form of
      illness.

PMID- 18043526
TI  - Impact of sociodemographic and clinical factors on subjective quality of life in
      schizophrenia patients in Beijing, China.
AB  - The impact of sociodemographic and clinical factors on subjective quality of life
      (SQOL) in Chinese schizophrenia outpatients was explored. Randomly selected
      subjects with schizophrenia (N = 273) were assessed with respect to their
      sociodemographic, clinical characteristics, and SQOL. Compared with the Chinese
      general population, patients had significantly lower scores in the physical and
      social SQOL domains. Multiple regression analyses revealed that depressive
      symptoms inversely predicted all SQOL domains; positive symptoms negatively
      predicted psychological, social, and environmental SQOL domains whereas
      educational level, extrapyramidal side effects, anxiety, history of suicide
      attempts, employment status, monthly income, number of hospitalization, and
      length of illness all significantly contributed to 1 or 2 SQOL domains.

PMID- 18043527
TI  - Thought disorder in euthymic bipolar patients: a possible endophenotype of
      bipolar affective disorder?
AB  - The search for psychological markers or for psychological endophenotypes for
      bipolar affective disorder has been frustrating, and the study of
      neuropsychological and neurocognitive functioning may be useful in this search.
      This article presents the results of a study comparing Rorschach protocols from a
      sample of adult euthymic bipolar patients (N = 18) and matched healthy controls
      (N = 8). Bipolar patients showed a higher proportion of immature responses and
      more instances of thought disorder; patients also showed significantly more
      severe thought disorder. These findings are discussed in the context of 2 related
      previous studies. We suggest that our modest series of studies using the
      Rorschach Inkblot Test provides preliminary evidence that certain variables
      especially the measures of thought disorder but possibly also the lack of
      emotional responses under cognitive "control" and the excessive proportion of
      immature content responses-may represent a possible endophenotype of bipolar
      disorder.

PMID- 18043528
TI  - A randomized controlled clinical treatment trial for World Trade Center attack
      related PTSD in disaster workers.
AB  - This article describes a controlled clinical trial of cognitive-behavioral
      treatment (CBT) for disaster workers. Despite high rates of PTSD in disaster
      workers worldwide, there have been no randomized trials of PTSD treatment.
      Participants were randomly assigned to a 12-week cognitive-behavioral exposure
      treatment (CBT, N = 15) or a treatment-as-usual (N = 16) condition. Eight CBT and
      14 treatment-as-usual participants completed treatment. An ANOVA examining
      changes in Clinician-Administered PTSD Scale scores found significant main
      effects of Time, Group, and a Time x Group interaction (p's < 0.010) with a
      significantly greater decline in symptom scores in the CBT group. Between-group
      effect sizes were large. Dropout was associated with lower income, less
      education, and higher alcohol consumption. This project demonstrates the
      feasibility of recruitment in the aftermath of a catastrophic event, the
      relevance of a brief focused intervention comprised of CBT and exposure, and the
      need to eliminate barriers to treatment retention associated with income and
      education.

PMID- 18043529
TI  - Symptoms of ecstasy dependence and correlation with psychopathology in Taiwanese
      adolescents.
AB  - This study aimed at examining the spectrum and frequency of symptoms of ecstasy
      dependence and their correlation with psychopathology by controlling
      polysubstance use in Taiwanese adolescents. Two hundred adolescents who had used
      ecstasy were recruited into this study. Symptoms of ecstasy dependence that had
      occurred in the preceding year were determined by an interview using the Kiddie
      epidemiologic version of the Schedule for Affective Disorders and Schizophrenia.
      The adolescents' psychopathology was examined using the Symptom Checklist-90
      Revised Scale. The proportion of participants who had symptoms of ecstasy
      dependence was calculated. The association between the number of symptoms of
      ecstasy dependence and psychopathology was examined by using stepwise multiple
      regression analysis. The results indicated that "continuing ecstasy use despite
      knowledge of having a problem related to ecstasy use," "spending a great deal of
      time in activities related to ecstasy use or to recover from its effects," and
      "ecstasy use tolerance" were the 3 most prevalent symptoms of dependence, and
      "withdrawal" was the symptom least reported. Heavy ecstasy use led to more
      symptoms of ecstasy dependence than light use. Symptoms of ecstasy dependence
      independently increased the risk of severe psychopathology after controlling the
      effects of polysubstance use. The results of this study indicated that
      adolescents were aware of the adverse effects of ecstasy use and that repeated
      ecstasy use would result in dependence on it. Screening the dependence symptoms
      of adolescent ecstasy users may help clinicians more thoroughly understand their
      psychopathology.

PMID- 18043530
TI  - Impact of defense style on brief psychotherapy of postpartum depression.
AB  - In this study, we evaluated the impact of defense style (DS) on outcome and its
      relation to the therapeutic alliance. Women with postpartum depression were
      allocated to a brief psychotherapeutic intervention. To evaluate DS and the
      therapeutic alliance, the Defense Style Questionnaire and the Working Alliance
      Inventory were employed. The main outcome was the Edinburgh Postnatal Depression
      Scale score at end point; anxiety and retention in treatment were also evaluated.
      Fifty-nine patients were included; 46 completed the therapy and 65.4% responded
      (Edinburgh Postnatal Depression Scale score <10). Intense use of immature
      defenses was related to persistence of depression and anxiety symptoms at end
      point, even when controlled for potential confounders. Results tended to confirm
      a hierarchy of DSs independently of the alliance. Clinicians should be aware of
      possible differential responses to brief psychotherapies related to DS.

PMID- 18043531
TI  - Pseudohysterical hemiparesis.
AB  - Four patients with the diagnosis of hysterical hemiparesis and normal magnetic
      resonance imagings were referred to us for further evaluation. All were being
      treated with antidepressant or antianxiety drugs or both, with no benefit. In all
      4 cases single photon emission computed tomography revealed decreased regional
      cerebral blood flow in frontal regions in cortical areas corresponding to their
      neurologic deficits. In all 4 cases improvement followed neurologic treatment. We
      suspect that reduced blood flow in frontal regions may have produced the
      neurologic deficits. We call these conditions "pseudohysterical hemiparesis."

PMID- 18043535
TI  - Report on the Fifth International Symposium on Radiohalogens (Whistler, BC,
      Canada, September 11-15th, 2004).

PMID- 18043536
TI  - Cross-bridged macrocyclic chelators for stable complexation of copper
      radionuclides for PET imaging.
AB  - Copper-64 (t(1/2)=12.7 h; beta+: 17.4%; E(beta+max)=656 keV; beta-: 39%; E(beta
      max)=573 keV) has emerged as an important non-standard positron-emitting
      radionuclide for positron emission tomography imaging of diseased tissues. A
      significant challenge of working with copper radionuclides is that they must be
      delivered to the living system as a stable complex that is attached to a
      biological targeting molecule for effective imaging and therapy. Significant
      research has been devoted to the development of ligands that can stably chelate
      (64)Cu, in particular, the cross-bridged (CB) macrocyclic chelators. This review
      describes the coordination chemistry and biological behavior of (64)Cu-labeled CB
      complexes.

PMID- 18043537
TI  - Bifunctional chelates for metal nuclides.
AB  - The use of ''non-standard'' metallic radionuclides continues to be an expanding
      field of investigation. Radiolabeling small molecules, peptides, proteins, and up
      to nano-particles are all areas of active investigation for both diagnostic and
      therapeutic applications. All require a common variableaethe need for appropriate
      chelation chemistry for adequate sequestration of the metallic radionuclide that
      is equal to the intended application. A brief overview of the array of the
      chelation chemistry options available to researchers and the means for their
      selection is provided.

PMID- 18043538
TI  - PET imaging problems with the non-standard positron emitters Yttrium-86 and
      Iodine-124.
AB  - AIM: Positron emission tomography (PET) imaging of non-standard positron emitters
      is influenced by gamma-coincidences, i.e. false coincidences produced by the
      coincident detection of an annihilation photon and a gamma-ray simultaneously
      emitted with the positron. The extent to which the PET study is disturbed by this
      effect is dependent on the kind of the positron emitter used, the kind and
      position of the object, the acquisition mode, i.e. the optional use of septa, and
      the reconstruction program. In order to demonstrate and study imaging problems
      with non-standard positron emitters, a phantom was scanned containing non
      radioactive rods with different absorption materials and filled with either
      (124)I or (86)Y in the bidimensional (2D) as well as tridimensional (3D)
      acquisition mode. METHODS: For reconstruction, the PET manufacturer's standard
      software without any modification was used. To reduce errors caused by the gamma
      coincidences, a simple linear background subtraction, estimated from the counts
      at the scanner's external radius, was applied. RESULTS: Without background
      subtraction, apparent positive and negative ''radioactivity concentrations'' were
      found in regions of interest positioned over the non-radioactive rods with values
      higher for (86)Y compared to (124)I and also higher for 3D compared to 2D. A
      complete subtraction of the background led to erroneous RESULTS: The errors in
      the phantom's non-radioactive rods and the difference between measured and true
      radioactivity became minimum, when about 75% of the background was subtracted.
      This refers to both the 2D and 3D mode. CONCLUSION: Quantitation problems with
      the non-standard positron emitters (124)I and (86)Y could be minimized in the
      phantom study examined here by using a simple background subtraction together
      with the manufacturer's standard correction and reconstruction procedures.

PMID- 18043539
TI  - Image quality with non-standard nuclides in PET.
AB  - Non-standard positron emission tomography (PET) nuclides bring with them the
      prospect of new chemistry leading the way to novel approaches for targeted
      imaging and therapy. In particular, the kinetic energy of the positron of some of
      these nuclides is high (as much as 4 MeV) and, thus, a highly specific PET probe
      can be very lethal to cancerous cells. However, the high positron energy will
      degrade the spatial resolution, and this degradation will be more important in
      high-resolution, small animal PET imaging, where most of the novel tracers are
      developed. This paper discusses the image quality in small animal PET imaging
      obtained with such nuclides. The nuclides of (60)Cu, (61)Cu and (64)Cu, (76)Br,
      (94)mTc, and (89)Zr will be particularly analyzed. The spatial resolution will be
      seen to degrade with nuclides with higher positron end-point energy, going from
      1.7 mm for (18)F to 2.2 mm for (76)Br, for example. Many of these novel PET
      nuclides decay by the emission of cascades gamma rays that are detected in
      coincidence with the positron annihilation photons which create additional noise
      on the images. However, the use of an image reconstruction algorithm, which
      includes a model of the statistical nature of nuclear decay and the modeling of
      the tomograph response, contributes to both improve the spatial resolution and at
      the same time reduce the image noise.

PMID- 18043540
TI  - Non-standard radionuclide production for PET in Japan.
AB  - There is a limited number of non-standard positron emission tomography (PET)
      radionuclides available in Japan. At the present time, non-standard PET nuclides
      ((64)Cu and (62)Zn/(62)Cu generator) are available from a medium energy cyclotron
      at the National Institute for Radiological Sciences in Chiba, Japan. Targetry for
      a small cyclotron has been installed on the cyclotrons of the University of
      Fukui. The production and distribution of these radionuclides from these
      cyclotrons will be described.

PMID- 18043541
TI  - Sustainable production of orphan radionuclides at Wisconsin.
AB  - Over a hundred proton-induced reactions have been studied at the University of
      Wisconsin Medical Physics department since the installation of the first CTI RDS
      112 in 1985. The focus has been to measure thick target yields at 11 MeV, in an
      effort to concentrate on the practical production of positron emitting
      radionuclides that have favorable decay characteristics, high yields and the
      potential for labeling pivotal biological tracers. This review covers our recent
      advances to scale-up the production of the heavy halogens and transition metals
      as feed-stock for non-conventional PET tracers that are currently attracting
      increased attention in oncology.

PMID- 18043542
TI  - Radionuclide production and yields at Washington University School of Medicine.
AB  - Washington University School of Medicine has carried out the production of ''non
      standard'' nuclides for the positron emission tomography (PET) community since
      1999 under the Radionuclide Resource for Cancer Applications grant R24 CA 86307
      funded by the National Cancer Institute. With the support from the grant, we have
      successfully developed procedures for the high yield production of a wide range
      of radionuclides and made them available to the research community. The following
      non-standard PET nuclides, (60)Cu, (61)Cu, (64)Cu, (76)Br, (77)Br, (124)I,
      (94m)Tc, and (86)Y are routinely produced on Washington University on-site
      Cyclotron Corporation CS-15 or Japan Steel Works 16/8 cyclotrons. Additionally, a
      technique to produce (45)Ti has been developed and lately, (89)Zr is being
      investigated. This paper describes the production techniques and presents the
      performance results in terms of yields and radionuclidic purity. Sufficient
      yields for distribution are achieved and high radionuclide purity is also
      achieved yielding high quality product for medical research.

PMID- 18043543
TI  - NCI Cancer Imaging Program efforts and their application to non-conventional
      radionuclides.
AB  - The US National Institute of Health (NIH) National Cancer Institute's Cancer
      Imaging Program funds research in cancer imaging. The article describes funding
      initiatives, such as Requests for Application and Program Announcement, funding
      mechanisms such as the R01 and R21, the Institutes of the NIH that fund imaging
      research, the application process, the application review process, and on-line
      resources to assist applicants for research funding for non-conventional
      radionuclides for imaging and therapy.

PMID- 18043544
TI  - Workshop on the production, application and clinical translation of ''non
      standard'' PET nuclides: a meeting report.
AB  - A one-day satellite workshop was organized to coincide with the 17(th)
      International Symposium on Radiopharmaceutical Sciences held in Aachen, Germany,
      April 30-May 4, 2007. The workshop, ''Production and application of non-standard'
      PET nuclides'', was held on Sunday April 29, 2007 at the Eurogress Aachen and was
      organized by J. Lewis, PhD, L. Tang, and M. Welch, PhD. The workshop was designed
      for the radiopharmaceutical community discussing the production, use and
      dissemination of the ''non-standard'' PET nuclides. The definition of ''non
      standard'' positron emission tomography (PET) nuclides included (45)Ti, (60)Cu,
      (61)Cu, (64)Cu, (66)Ga, (72)As, (74)As, (76)Br, (86)Y, (89)Zr, (94)mTc and
      (124)I. The workshop was supported by the grant Research Resource for Cancer
      Applications (R24 CA86307) funded by the National Cancer Institute at the
      National Institutes of Health. The workshop was attended by over 110 scientists
      and engineers from over 20 countries from all over the world and was designed
      with an open forum style to allow for discussions and interactions by all
      participants. All of the invited speakers were asked to make a contribution to
      this edition of the Quarterly Journal of Nuclear Medicine. The individual
      articles following this introduction are reviews of their area of expertise and
      the current state-of-the-art. This introduction briefly describes the role of the
      workshop, the aims and the general outcome. Also, the translation of these
      nuclides to the clinic, perhaps the most important goal of this work is discussed
      in this introductory article.

PMID- 18043545
TI  - The need of appropriate brain SPECT templates for SPM comparisons.
AB  - AIM: Statistical parametric mapping (SPM) is used worldwide to compare brain
      perfusion single photon emission computed tomography (SPECT) data. The default
      template within the SPM package used for SPECT image normalization includes
      images of a group of healthy subjects studied with [(99m)Tc]HMPAO. Since
      [(99m)Tc]HMPAO and [(99m)Tc]ECD have shown to distribute differently in SPECT
      studies, we formulated the hypothesis that comparing set of [(99m)Tc]ECD data
      normalized by means of a [(99m)Tc]HMPAO template may lead to incorrect results.
      METHODS: A customized [(99m)Tc]ECD template was built with SPECT and magnetic
      resonance imaging (MRI) images of 22 neurologically healthy women. Then, two sets
      of subjects, i.e. a group of patients with very early Alzheimer's disease (eAD)
      and a matched control group, studied by means of [(99m)Tc]ECD SPECT, were chosen
      for comparisons. The same statistical approach (t-test between eAD patients and
      controls and correlation analysis between brain SPECT and a cognitive score) was
      applied twice, i.e. after normalization with either the default [(99m)Tc]HMPAO
      template or the customized [(99m)Tc]ECD template. RESULTS: In the comparison
      between eAD and controls, a cluster of difference in the posterior cingulate
      gyrus of both hemispheres was only highlighted when using the customized
      [(99m)Tc]ECD template, but was missed when using the default [(99m)Tc]HMPAO
      template. In the correlation between brain perfusion and a cognitive score, the
      significant cluster was more significant and far more extended, also including
      the right superior temporal gyrus, using the customized [(99m)Tc]ECD template
      than using the default [(99m)Tc]HMPAO template. CONCLUSION: These data suggest
      the need of customized, radiopharmaceutical-matched SPECT templates to be used
      within the SPM package. The present customized [(99m)Tc]ECD template is now
      freely available on the web.

PMID- 18043548
TI  - Meaning of elevated CA 19-9 serum levels in chronic hepatitis and HCV-related
      cirrhosis.
AB  - AIM: Carbohydrate 19-9 antigen (CA 19-9) has been used in the diagnosis and
      follow-up of gastrointestinal tumors. However, a remarkable reduction of
      specificity has been described in subjects with chronic diseases. Elevated CA 19
      9 serum levels have been described in non neoplastic liver diseases, such as
      hepatic cirrhosis, where they correlate with the fibrosis grade and the disease
      severity. The aim of the study is to evaluate CA 19-9 levels in chronic hepatitis
      patients (CH) and hepatic cirrhosis patients, Hepatitis C Virus (HCV)-correlated.
      Our goal was to establish whether elevated CA 19-9 levels can be considered a non
      casual event in chronic liver disease and whether a correlation can be found
      between CA 19-9 levels and the severity of the disease. METHODS: 116 patients
      have been recruited (76 m, 40 f, average 54 years); 56 patients were affected by
      CH and 60 by hepatic cirrhosis (Child A). All patients were HCV+, genotype 1b.
      Patients positive to CA 19-9 high levels were subjected to abdominal echography,
      EGDS, colonscopy, abdominal CT. RESULTS: Fifty two percent presented high levels
      of CA 19-9. None was affected by intestinal or pancreatic neoplasia, or
      colestatic icterus. CA 19-9 levels were elevated in 46% of patients with chronic
      hepatitis, and in 54% in patients with hepatic cirrhosis. Furthermore, CA 19-9
      levels in hepatic cirrhosis compared to CA 19-9 levels in chronic hepatitis was
      statistically significant (P>0.007). CONCLUSION: Increased serum levels of CA 19
      9 are frequent in chronic viral hepatitis; this often does not indicate a
      contemporary neoplastic disease and correlates in a statistically significant way
      (P>0.007) with the severity of the disease.

PMID- 18043550
TI  - DLCO correlates with intestinal inflammation in ulcerative colitis, but
      albuminuria does not.
AB  - AIM: The aim of this study was to evaluate the frequency of carbon monoxide
      diffusing capacity (DLCO) impairment and microalbuminuria in patients with active
      ulcerative colitis (UC) and to assess whether these nonexpensive and noninvasive
      tests correlate with intestinal inflammation. METHODS: A prospective
      observational study was set up at the Fiorenzuola Hospital and performed during a
      4-year period. We enrolled 30 consecutive subjects with clinical and histological
      diagnosis of active UC and 20 healthy subjects matched for age and sex. After
      full colonscopic assessment with multiple mucosal biopsies, the clinical disease
      activity of each patient was quantified. A global spirometry and 24-h urine
      collection at rest to measure microalbuminuria were performed. Each biopsy
      specimen was assessed blindly by a histopathologist, who assigned a score
      according to the severity of enterocyte damage, cryptitis and acute and chronic
      inflammation of the lamina propria. RESULTS: A latent pulmonary involvement with
      a reduction in DLCO was present in 20 patients (67%). A subclinical renal
      involvement with microalbuminuria was detected in 19 subjects (63%). The mean
      DLCO was 78.2+/-15.2 in Group 1 vs 94.7+/-13.1 in Group 2 (P<0.001).
      Microalbuminuria was 103.6+/-90.8 in Group 1 vs 57+/-31.7 in the control group
      (P=0.062). DLCO reduction correlated significantly with intestinal
      histopathological grading in Group 1 (r = -0.742, P< 0.001), although there was
      no correlation between microalbuminuria and histological grading (r = -0.273, P=
      0.143). CONCLUSION: Our data confirm that latent pulmonary involvement (DLCO
      impairment) and microalbuminuria are frequent in UC. The DLCO may provide a
      useful noninvasive indicator of colonic inflammation in subjects with UC and
      concomitant subclinical lung involvement.

PMID- 18043549
TI  - Prognostic factors of survival in complicated viral and alcoholic cirrhosis
      without hepatocellular carcinoma. A retrospective study.
AB  - AIM: In several studies, attention is needed to one specific complication, in
      particularly to hepatocellular carcinoma, which modifies the natural history of
      liver cirrhosis. Thus, we performed a retrospective cohort analysis to clarify
      which complications, alone or in combination, are predictive factors of mortality
      in patients with viral or alcoholic cirrhosis without hepatocellular carcinoma.
      METHODS: Case records of 255 patients with decompensated viral or alcoholic
      cirrhosis between January 1990 and December 2000 were retrospectively analyzed.
      Relevant clinical and laboratory parameters, and their relationship to mortality,
      were studied. RESULTS: The mean duration of follow-up period was 29 months in
      which 178 patients (69.8%) died and 77 (31.8%) survived. None of the patients
      underwent liver transplantation. The cumulative mortality rate of patients with
      complicated cirrhosis was 38.8% after 1 year, 51.7% after 2 years, 61.1% after 3
      years and 65.1% after 8 years. A multivariate Cox's model identified the
      following variables as significant: age (P=0.001), gastrointestinal bleeding (GB)
      ascites combination (P=0.000), encephalopathy-GB-ascites (P=0.028), hepatorenal
      syndrome (HRS) (P=0.000), GB-spontaneous bacterial peritonitis (SBP) (P=0.001),
      alkaline phosphatase (ALP) (P=0.004) and the Child-Pugh score (P=0.000).
      CONCLUSION: The mortality in a group of patients with alcoholic cirrhosis is
      longer than in those with viral cirrhosis . Moreover, ascites in combination with
      other complications, HRS and hemorrage-SBP association are independent predictors
      of mortality in patients with complicated liver cirrhosis.

PMID- 18043551
TI  - Trace element levels in adult patients with proteinuria.
AB  - AIM: Trace elements are involved in many metabolic processes. They circulate
      prevalently bound to protein. In literature few studies deal with metal
      metabolism in adult patients with proteinuria, so we decided to further
      investigate metal metabolism in proteinuric patients. METHODS: We studied 27
      patients (14 male, 13 female), mean age 61.6+/-17 years with different degrees of
      renal function, serum albumin and proteinuria. Metal concentrations of copper
      (Cu), zinc (Zn) and aluminum (Al) were measured in serum and urine. No patient
      had environmental exposure to these metals. RESULTS: The serum Zn level was below
      the normal range in 11 patients. The serum Cu level was reduced in 5 patients.
      The Al serum level was elevated in 4 patients. Six patients had reduced and 6
      patients had elevated Zn excretion. The urinary Cu excretion was elevated in 6
      patients. The urinary Al excretion was elevated in 1 patient. Trace metal
      concentrations were related neither to renal function nor to total serum protein
      or albumin levels. Serum zinc was directly correlated with proteinuria and
      urinary zinc and negatively correlated with testosterone levels in both sexes.
      CONCLUSION: Adult patients with proteinuria have several modification of trace
      metal concentration in serum and urine. Serum concentration of metals did not
      depend on renal function or serum protein levels. Urinary Zn excretion was
      directly related to proteinuria and serum Zn levels. A negative correlation
      between serum Zn levels and testosterone was found in both sexes. Renal failure
      reduced urinary excretion of Cu and Al.

PMID- 18043552
TI  - Viral hepatitis after liver transplantation. Which immunosuppressive drugs should
      be recommended?
AB  - Treatment of hepatitis C after liver transplantation can be challenging as graft
      rejection and graft hepatitis caused by hepatitis C virus (HCV) may be difficult
      to distinguish. Immunosuppressive medications may significantly alter the course
      of hepatitis C in liver transplant recipients. Moreover, single substances have
      been shown to display antiviral effects in vitro while others are believed to
      have antifibrotic properties. This review summarizes the modes of action of
      different classes of immunosuppressive drugs used after liver transplantation and
      discusses pros and cons of individual drugs in the setting of HCV infection. No
      definite recommendation for an optimal immunosuppressive regimen can be given at
      this stage. The most important lesson learned during the last two decades is that
      acute rejection episodes have to be avoided in particular in hepatitis C since
      these are associated with reduced graft and patient survival. Further trials are
      urgently needed to clarify the role of different immunosuppressive compounds in
      hepatitis C after transplantation.

PMID- 18043553
TI  - From colonic polyps to colon cancer: pathophysiology, clinical presentation,
      screening and colonoscopic therapy.
AB  - Colon cancer is the most common nondermatologic cancer in Italy and throughout
      Europe, with about 250,000 cases annually in Europe, about half of whom die. Yet,
      colon cancer is largely preventable through intensive, mass screening programs to
      remove premalignant colonic polyps. The persistently high incidence and mortality
      is largely due to ineffective implementation of established screening protocols
      due to patient fears about screening tests, physician under-referral for
      screening, and test costs. Colon cancer mostly arises from adenomas, recognized
      as colonic polyps, but may occasionally arise from the sessile serrated adenoma.
      Adenomatous polyposis coli (APC) gene mutation is the key molecular step in
      adenoma formation. Mismatch repair gene mutation is a less common alternative
      pathway. Progression from adenomas to colon cancer is a multistep process,
      involving mutations of the DCC, k-ras, and p53 genes; loss of heterozygosity in
      which cells loose one allele of some genes from chromosomal loss; and DNA
      methylation which can silence DNA expression. Numerous environmental factors can
      increase the risk of colon cancer, presumably by modulating these molecular
      pathways. While colon cancer in an advanced and incurable stage often produces
      clinical findings, premalignant adenomatous polyps and early, highly curable,
      colon cancer are often asymptomatic. This phenomenon renders adenomas or early
      cancers difficult to detect by clinical presentation and provides the rationale
      for mass screening of asymptomatic adults over 50 years old for early detection
      and prevention of colon cancer. Colonoscopy is the primary screening test. All
      polyps identified at colonoscopy are removed by colonoscopic polypectomy.
      Endoscopic mucosal resection is required for deeply penetrating noncancerous
      polyps. Colonoscopy is repeated every ten years if the index colonoscopy revealed
      no lesions, but is repeated more frequently if adenomatous polyps were identified
      at this colonoscopy due to an increased risk of subsequent polyps or colon
      cancer. Flexible sigmoidoscopy every few years with annual fecal occult blood
      testing is a significantly less sensitive screening protocol. Virtual colonoscopy
      is controversial as a screening test due to widely variable reported RESULTS:
      Computerized tomography is standardly used to preoperatively detect distant colon
      cancer metastases, while endosonography is being increasingly used for
      locoregional staging of rectal cancer. Stool genetic markers and videocapsule
      endoscopy are promising, but currently experimental, screening tests.

PMID- 18043554
TI  - Nutrition and fertility.
AB  - The first studies about fertility and nutrition date back to the 70ies and
      already showed a strict relation among female fertility, weight and body
      composition. However, the mechanisms of this connection started to be explained
      only after leptin's discovery. According to some authors' opinion, leptin could
      interact with reproductive axis at multiple sites with stimulatory effects at the
      hypothalamus and pituitary and stimulatory or inhibitory actions at the gonads.
      Leptin could play a role in other physiologic processes such as menstruation and
      pregnancy, and could initiate the complex process of puberty. It has been showed
      that conditions in which nutritional status is suboptimal, such as eating
      disorders, exercise induced amenhorrea, functional hypothalamic amenhorrea and
      polycystic ovarian syndrome, are associated with abnormal leptin levels. These
      conditions, are characterized by severe changes in body composition and dietary
      habits. Since leptin is regulated by body composition and dietary factors, (such
      as energy intake and macronutrient composition), a strict connection between
      nutritional intake and fertility regulated by leptin is confirmed. This review
      focuses on the current knowledge about nutritional factors that influence leptin
      levels. Since clinical and subclinical nutritional imbalance can determine the
      development and the maintenance of neuroendocrine and metabolic aberrations,
      studies on fertility need a deeper attention about dietary habits and nutritional
      status.

PMID- 18043555
TI  - Clostridium difficile-associated disease with lethal outcome in a 77-year-old
      woman. A case report.
AB  - Clostridium difficile-associated disease (CDAD) ranges in severity from mild
      diarrhoea to fulminant colitis and death. Antimicrobial use is the primary risk
      factor for development of CDAD. C. difficile typically affects older or severely
      ill patients, hospitalized or residents in long-term-care facilities. We report a
      case of CDAD in a 77-year-old woman operated on for cholecystitis calculosa and
      treated with cephalosporins and aminoglycosides. Symptoms and signs of CDAD were
      watery diarrhoea, mucus stool, high fever and, weakness. Sigmoidoscopy was
      provided on the second day after hospitalization. It revealed diffuse
      pseudomembranes throughout the distal colon, confirming C. difficile infection.
      Antimicrobial agents administered at the admission were stopped and treatment
      with oral vancomycin, metronidazole and famotidine was initiated. Despite this
      the patient's status worsened and she died because of cardiogenic shock.

PMID- 18043556
TI  - Is a gluten-free diet necessary in patients with potential celiac disease?
AB  - Potential celiac disease is characterized by a normal duodenal mucosa despite
      high intraepithelial lymphocytes count and/or positive endomysial antibodies
      while on a gluten-containing diet. An agreement about the management of this
      condition is still lacking. A 68-year-old lady complaining of weight loss and
      epigastric pain was found to be affected by potential celiac disease. Although
      she maintained a gluten-containing diet, epigastric pain and weight loss
      disappeared. If she had started a gluten-free diet, the improvement would have
      been considered a demonstration of the beneficial effect of the diet. Potential
      celiac patients can be maintained on a gluten-containing diet providing they are
      closely followed up.

PMID- 18043557
TI  - Coronary heart disease in women: battle is won, but the war remains.
AB  - According to the most recent report of the US National Heart, Lung, and Blood
      Institute, mortality from coronary heart disease has declined in women from one
      in three to one in four. Due to massive campaigning efforts in educating the
      medical community and the general public, coronary heart disease has become
      increasingly recognized as a woman's disease. Indeed, it is the number one killer
      in women, exceeding cancer and infectious diseases. Numerous observational
      studies, clinical trials, and reports have indicated that there are gender
      specific differences in the presentation, diagnosis, treatment, and outcomes of
      coronary heart disease. One common theme, not only in United States, but world
      wide is the underutilization of known and validated medical and interventional
      therapies in women compared to men. Even though previously conducted large,
      randomized controlled trials had limited numbers of women, recent large scale
      cardiac trials in women have enabled the development of evidence-based guidelines
      for coronary heart disease diagnosis and management in women. Importantly,
      menopausal hormone therapy and antioxidant vitamin therapy do not protect post
      menopausal women from coronary heart disease. Aggressive life-style and
      pharmacologic management of known coronary risk factors in women should be a top
      priority to improve coronary heart disease morbidity and mortality. Research data
      continue to emerge to fill the gaps of how gender affects atherosclerosis; in the
      meantime, continued patient and physician education to increase awareness of
      coronary heart disease may help to eliminate some of the gender-based disparities
      in the delivery of coronary care to women.

PMID- 18043558
TI  - [Mechanical reperfusion in patients with acute myocardial infarction].
AB  - Natural history of patients with acute myocardial infarction has significantly
      improved in the last 20 years. The main reason for this progress was the
      introduction of effective reperfusion strategies. It has been clearly documented
      that the speed, extension, and duration of reperfusion are key prognostic
      factors. Mechanical reperfusion during primary percutaneous coronary
      interventions has been shown to be superior to fibrinolysis in order to achieve
      these RESULTS: All the techniques able to positively interact with the ischemia
      reperfusion process and that have been evaluated so far (stent, adjunctive
      pharmacological therapy, anti-embolic devices, etc.) will be discussed.

PMID- 18043559
TI  - Electrical storm: clinical manifestations and management.
AB  - Electrical storm is the clustering of hemodynamically destabilizing ventricular
      tachycardia or ventricular fibrillation that typically requires multiple
      electrical cardioversions or defibrillations within a 24-hour period. Electrical
      storm is frequently seen in the acute phase of myocardial infarction, in patients
      with the genetic arrhythmia syndromes, and in patients with implanted
      cardioverters-defibrillators. The evaluation and management should focus on the
      immediate suppression of the arrhythmia, a search for possible reversible causes,
      and attempts to prevent recurrences. In this review we present the most common
      conditions associated with electrical storm, therapeutic options for suppression
      of electrical storm, and new investigational techniques emerging for the
      treatment of electrical storm in refractory cases. The management of this life
      threatening arrhythmia typically requires the coordinated efforts of emergency
      medicine, critical care, cardiology, cardiac electrophysiology, and pacemaker
      experts.

PMID- 18043560
TI  - Update in the treatment of neurally-mediated syncope.
AB  - Syncope is a transient, self-limited loss of consciousness, usually leading to
      falling. The underlying mechanism is a transient global cerebral hypoperfusion.
      Since there are many causes of syncope, a specific treatment cannot be
      administered without knowing of the exact mechanism responsible of loss of
      consciousness. Drugs are ineffective. The main therapeutic innovations of the
      most recent years are isometric counter-pressure maneuvres, lower limb
      compression bandage and therapy guided by implantable loop recorder in patients
      with recurrent suspected neurally-mediated syncope.

PMID- 18043561
TI  - Management of urological hemorrhage and the role of transarterial
      angioembolization.
AB  - Urological hemorrhage is an important problem in contemporary urological practice
      with significant associated morbidity and mortality. Furthermore, these
      emergencies present a number of challenges to clinicians as current practice has
      evolved due to the increased availability of new imaging techniques and
      transarterial embolisation (TAE). In this review we have explored the
      epidemiology, etiology and management of both renal and bladder hemorrhage. Renal
      bleeding secondary to accidental or iatrogenic trauma and neoplastic disease
      requires careful but expeditious assessment and treatment. We have described
      current conservative, surgical and radiological approaches to the management of
      this challenging problem. Moreover, bladder hemorrhage due to hemorrhagic
      cystitis, boadder cancer and infection represents a significant problem in
      current practice. Advances in technology have changed the management options and
      again we have explored the literature in order to determine the optimum treatment
      approaches.

PMID- 18043562
TI  - Emergency psychiatry.
AB  - Up to 15% of people that are visited in the Emergency Department of a Hospital
      have a mental disorder and/or a psychiatric symptom: often this is not recognized
      or not properly treated. The reasons for this are more than one and involve: the
      emergency physicians that are not always prepared and sensible to face this kind
      of disorders; the psychiatrists that are not always well tuned with the language
      and the clinic of the emergency; and the patients, that can ignore or deny the
      psychiatric nature of their problems. After an initial definitions of the most
      important terms and concepts (Psychiatric Emergency and Urgency, Behavioral
      Emergency, Acute Presentations of Mental Disorders, and Crisis) the Medical and
      Psychiatric Assessment are discussed with different Clinical Presentations and
      Classifications, Psychosocial Evaluation and Risk Assessment. Finally the
      Clinical Management and the Pharmacological Treatment are presented with special
      attention to the underlying medical causes and to the use of new drugs,
      especially second generation antipsychotics, alone or combined with
      benzodiazepines.

PMID- 18043563
TI  - The evaluation and management of acute poisoning emergencies.
AB  - Emergency physicians will regularly be called upon to care for poisoned patients.
      The purpose of this article is to review the general approach to the poisoned
      patient. Specific signs and symptoms will be identified that may clue the
      clinician into a specific toxin class as a diagnosis. Necessary testing in
      poisonings will be highlighted. This article will also introduce the basics of
      gastrointestinal decontamination and antidotes against select poisons.

PMID- 18043564
TI  - Current approach to burn critical care.
AB  - Burn trauma is a frequent cause of morbidity and mortality all over the world.
      Advancements in resuscitation, surgical tecniques, infection control and
      nutritional/metaolic support decreased mortality and morbidity. This article
      intends to review current outlines for initial treatment and resuscitation
      nutritional/metabolic support and wound management peculiar to burn patients.

PMID- 18043565
TI  - Meningococcal disease: a review on available vaccines and vaccines in
      development.
AB  - Meningococcal disease continue to have a major public health impact in many
      countries. Five major groups of Neisseria meningitidis (A, B, C, Y and W135) are
      responsible for most meningococcal diseases. Plain polysaccharides vaccines for
      Neisseria meningitidis groups A, C, Y and W-135 have been in use for
      approximately 20 years, both to prevent invasive disease in high-risk population
      and to control disease outbreaks. However, these conventional meningococcal
      vaccines induce a relatively short-lasting T-cell independent immune response,
      are not effective in children under two years of age and can induce
      hyporesponsiveness. New meningococcal group C conjugate vaccines have since been
      developed, which offer solid advantages over the currently licensed plain
      polysaccharide vaccines. Tetravalent serogroup A, C, Y and W135 meningococcal
      vaccines are under development and one has already been licensed. There is still
      no universal vaccine available against the serogroup B, which is a major cause of
      invasive disease. This report summarises the different approaches to the
      development of vaccines against the pathogenic meningococci.

PMID- 18043566
TI  - [The role of natriuretic peptides in heart failure].
AB  - Over the last decades, there has been a significant increase in incidence and
      prevalence of heart failure, a major cause of cardiac morbidity and mortality.
      Measurements of neurohormones, in particular B-type natriuretic peptide (BNP),
      can significantly improve diagnostic accuracy, and also correlate with long-term
      morbidity and mortality in patients with chronic heart failure presenting to the
      emergency department. BNP is secreted by cardiac ventricles mainly in response to
      wall stress and neurohormonal factors like the sympathetic nervous system,
      endothelins, and the rennin-angiotensin-aldosterone system. BNP increases
      myocardial relaxation and oppose the vasoconstrictive, sodium retaining, and
      natriuretic effects caused by vasoconstrictive factors. BNP is the first
      biomarker to prove its clinical value for the diagnosis of left ventricular
      systolic and diastolic dysfunction but also for the right ventricular
      dysfunction, guiding prognosis and therapy management. Emerging clinical data
      will help further refine biomarker-guided therapeutic and monitoring strategies
      involving BNP.

PMID- 18043567
TI  - Targeted therapies in solid tumours: results and promises.
AB  - In these last few years novel approaches to the treatment of solid tumours have
      been proposed. Therapeutic agents addressed to specific functions of the
      neoplastic cells seems to be very promising tools, with a low grade of
      toxicities. These agents are the basis of the so called targeted therapies. Small
      molecules inhibiting the proliferative cascade of the cancer cells and monoclonal
      specific antibodies against growth factor or vascular endothelial growth factor
      have been claimed as the promise in cancer therapy. Unfortunately, the very good
      results obtained in preclinical experiments have not been completely confirmed in
      the clinical practice. A selection of patients who could have beneficial effects
      from the novel agents is mandatory to avoid inappropriate therapies and also
      unjustified expenses.

PMID- 18043568
TI  - Mini-invasive techniques for the treatment of female stress urinary incontinence.
AB  - AIM: The aim of this study was to review recent literature on mini-invasive
      surgical technique for the treatment of female stress urinary incontinence (SUI).
      Surgical aspects, intraoperative and perioperative complications and objective
      and subjective outcomes were analyzed and compared. METHODS: The PubMed databank
      from 2000 to February 2007 was searched for original prospective and randomized
      studies in English, on surgical treatment of female SUI, which avoided a
      laparotomic access to the female pelvis. Studies had to investigate at least 40
      women with a minimum follow-up of 12 months. RESULTS: A total of 38 prospective
      studies were found: 27 of them were on mid-urethral slings; 8 assessed urethral
      injections; and 3 radiofrequency treatment. Fifteen studies were randomized.
      Follow-ups ranged from 12 to 60 months, except for sexual function which had a 6
      month follow-up. Ten out of 38 studies assessed patients who did not refer pelvic
      organ prolapse or detrusor overactivity and had not undergone any previous anti
      incontinence procedure. CONCLUSION: Mid-urethral slings showed good outcomes and
      are safe and brief to perform and have a relatively short learning curve.
      Urethral injections showed discouraging results, as they have poor outcomes and
      repetitive treatments are frequently necessary. Injections can be used in women
      with contraindications to major surgical procedures, with intrinsic sphincter
      deficiency as the main cause of incontinence. Radiofrequency showed worse results
      than mid-urethral slings and is a valuable choice in women who refuse more
      invasive procedures. The development of studies with longer follow-ups on mini
      invasive surgical techniques are encouraged.

PMID- 18043569
TI  - Twin pregnancy: not only a medical event.
AB  - AIM: Twin pregnancies are at greater risk of obstetrical and perinatal adverse
      outcome compared to singletons. In addition, expecting twins can have particular
      psychological consequences on both parents. The aim of our study was to interview
      women with a twin pregnancy and their partners in order to assess their feelings
      and emotions related to the twins and to evaluate the opportunity to activate an
      information group about the theme of twin pregnancy, and a development of twins
      and family management. METHODS: Twenty patients with an uncomplicated twin
      pregnancy and their partners answered 9 questions in a semistructured interview,
      set on the basis of the psychological and social issues reported in the
      literature on couples expecting twins. Emerging themes and key words were
      extracted from the interviews and analysed. RESULTS: Quantitative analysis showed
      that women were, in most cases, shocked at the time of the diagnosis of twinning,
      while men tried to minimize the worries of their partners. Women reported some
      fears related to the practical management of the future life, but they declared
      to feel not different from women expecting singleton, confirming the data
      reported in the literature. Seventy percent of the women were interested in
      meeting other parents with twins. Qualitative analysis frequently indicated the
      defence mechanism of rationalisation and negation of the worries concerning the
      pregnancy risks and the future care of their babies. Their answers seem to hide
      fears and doubts that are confessed with difficulty. CONCLUSION: Our study
      suggests the importance for hospital staff to create an atmosphere of calm and to
      demonstrate empathy and understanding, with the aim to help and allow the mothers
      to express their fears.

PMID- 18043570
TI  - Relationship between Helicobacter pylori seropositivity and hyperemesis
      gravidarum with the use of questionnaire.
AB  - AIM: The aim of the present study was to investigate the relationship between
      Helicobacter pylori (HP) infection and Hyperemesis gravidarum (HG) by using a
      questionnaire. METHODS: Twenty-five pregnant women with HG and 85 asymptomatic
      pregnant women (aged 14-40) of matching gestational age were enrolled between
      October 2004 and January 2006. Anti-HP immunoglobin G (IgG) serum antibody was
      tested to establish seropositivity. In our study we used a multi variable
      questionnaire (name, age, gravida, number of vomits daily etc.). The results were
      analyzed using chi squared and Mann-Whitney U- test. RESULTS: The prevalence of
      HP infection was 56% (14 of 25) among patients with Hyperemesis gravidarum and
      48.2% (41 of 85) among control subjects (P>0.05, chi squared test). In the same
      study the HP seropositivity is not related to age of the woman (50%, 55 of 110
      were HP positive, P>0.05 chi squared test) but there was a significantly
      association between number of deliveries and HP seropositivity (primigravida [+]
      34.2% versus 65.8%, multigravida [+] 6.1% versus 38.9%, P<0.05 chi squared test).
      The history for gastrointestinal problems of the tested women and their husbands
      is not related to HP seropositivity(38.1% positive for HP and with
      gastrointestinal disorders she/he or both versus 61.8% positive and without
      problems both, P>0.05, Mann-Whitney U- test). Finally there was no relativity
      between the number of vomits daily and the HP seropositivity (48.2% with HP [+]
      and 0-3 vomits daily versus 56% with HP [+] and 4-8 vomits daily, P>0.05 chi
      squared). CONCLUSIONS: Our findings do not support any direct correlation between
      HP seropositivity and Hyperemesis gravidarum, number of vomits daily, age of
      woman, history for gastrointestinal problems but only with the number of
      deliveries.

PMID- 18043571
TI  - [Comparison between lymphocytic infiltration in early spontaneous abortions and
      in elective abortions with signs of disruption at the chorio-decidual interface].
AB  - AIM: The aim of the study was to compare lymphocytic infiltrations in early
      spontaneous abortions with those with signs of disruption at the chorio-decidual
      interface in elective abortions. Determinations were performed on preparations
      received at the Anatomy-Pathology Services of Ospedale San Paolo, Savona (Italy)
      in 2005. METHODS: Immunohistochemistry studies were performed using antisera CD3,
      CD4 and CD14 with a DAB detection kit on a Ventana BenchMark automated slide
      staining system. The material was grouped into three classes: early spontaneous
      abortions (class 1); elective abortions with signs of disruption at the chorio
      decidual interface (class 2); elective abortions without such signs (class 3).
      RESULTS: Preparations from classes 1 and 2 shared a similar picture of
      lymphocytic activation and the presence of macrophagic elements. The test results
      demonstrated that the proportion of the T cell population increased with the rise
      in CD8+ lymphocytes in both class 1 and class 2 preparations. CONCLUSION: The
      results indicate that T-cell-mediated immune activation may the cause or one of
      the causes of spontaneous abortion and that the effects of disruption at the
      chorio-decidual interface observed in elective abortion provide a clue to initial
      signs of loss of pregnancy. From the discovery of a population without evident
      signs of active abortion (elective abortion with a disturbed chorio-decidual
      interface) but with evidence of initial lymphocytic activation compared with that
      devoid of such signs (elective abortion) one can conjecture that lymphocytic
      activation is a major factor in the process leading to early spontaneous
      abortion.

PMID- 18043572
TI  - Fertility after non-surgical management of the symptomatic first-trimester
      spontaneous abortion.
AB  - AIM: The aim of this study was to assess clinical outcome after a non-surgical
      management of the symptomatic spontaneous abortion in the first-trimester of
      pregnancy in a level III maternity hospital and to assess the subsequent
      fertility of the study population. METHODS: A prospective study in which 70 women
      with a symptomatic early pregnancy loss undergone an expectant management of
      miscarriage was performed. If resolution was not obtained after 4 days, medical
      treatment with misoprostol was administered. The patients were followed-up after
      the first menstrual cycle with a medical examination and an ultrasound scan.
      After 12 months, the patients were interviewed by phone to investigate on
      possible complications of abortion and on the occurrence of new pregnancies.
      RESULTS: The non-surgical management of miscarriage was successful in 68 out of
      70 women (97%). Surgical intervention was necessary in 2 of 70 women (3%).
      Bleeding and pain were described as slightly more than a normal menstrual cycle.
      Among the 60 patients that answered at the 12-month follow-up (85.7%), none
      reported gynecological troubles and the subsequent pregnancy rate of the women
      was 81%. CONCLUSION: Expectant management of selected cases of spontaneous
      abortion, associated to medical treatment in indicated cases, could offer a valid
      alternative to dilatation and curettage.

PMID- 18043573
TI  - [Cesarean section, techniques and skin suture materials].
AB  - AIM: The aim of the study was to compare the outcome, complications and costs of
      three skin suture techniques after Caesarean section. METHODS: The study sample
      was 310 women who underwent caesarean section between 2003 and 2007. The sample
      was divided into three groups: an intradermal suture with non-reabsorbable thread
      was applied in 98; metallic clips were placed in 90; 2-octyl-cyanoacrylate (2
      OCA) glue was used for wound closure in 112. The sutures were checked at 4 days
      and 2 months after the operation to determine cosmetic outcome, patient
      compliance, strength of incision closure, allergic reactions, suture infection,
      and total cost of each technique. RESULTS: No substantial differences in strength
      of incision closure or cosmetic outcome between the techniques were found.
      Compliance was better in the group that received 2-OCA, while the total cost of
      suture alone was lower in the group that received the non-reabsorbable
      intradermal suture. CONCLUSION: The results suggests that following Caesarean
      section according to Stark, skin suture with 2-OCA glue has the advantage of
      greater patient compliance, while intradermal thread suture is less costly with a
      cosmetic outcome comparable to that of the other two techniques.

PMID- 18043574
TI  - Pelvic organ prolapse: a review of the current literature.
AB  - Pelvic organ prolapse has afflicted women since the beginning of mankind. Even
      though we have been faced with this problem for so many centuries, we still have
      not found a way to overcome gravity and prevent prolapse. We continue to make
      efforts to manage prolapse, modifying our techniques based on burgeoning
      research. This knowledge helps us to avoid repetitive complications from surgery
      and to improve techniques to prevent recurrent prolapse. In addition, we are
      constantly adapting our methods depending on available technology. With an aging
      population, the demand for physicians and surgeons trained in management of
      pelvic organ prolapse will increase. The rapidly evolving literature on pelvic
      organ prolapse makes a comprehensive review difficult. However, based on the
      current literature, randomized controlled trials are needed to compare new
      prolapse repair techniques to traditional techniques. Physicians specializing in
      surgical management of pelvic organ prolapse will need to work together to
      complete quality clinical trials. The primary focus of this review will be on the
      recent research concerning the epidemiology, etiology, presenting symptoms, and
      diagnosis of pelvic organ prolapse. We will also discuss the different types of
      prolapse by compartments of the vagina in which they occur and how each of these
      types of prolapse can be managed. Finally, we will review recent literature
      evaluating surgical repairs using transvaginal mesh kits.

PMID- 18043575
TI  - Doctors and the chronic pelvic pain patient.
AB  - Many women with chronic pelvic pain (CPP) turn out not to have any identifiable
      pathology despite having undergone multiple investigations. There is no consensus
      as to the best management for women in this group. Although a multidisciplinary
      approach to diagnosis and care has been advocated as best practice, it is costly
      and not practical in most units in the United Kingdom, and many other countries.
      Clinicians need to be aware of the importance of attitude and medical
      consultation as factors influencing patients' outcome from investigation and
      treatment. While consulting styles reflect the individual personality of the
      doctor, we need to be aware of our own underlying attitudes and how these might
      enter into the dynamics of the consultation. Some patients may want to have open,
      non-directive consultations, some more directive consultation styles. It is,
      therefore, essential for the physicians to identify patients' expectations or
      preferences and then try to meet them, in order to attain "concordance" in
      communication. In this chapter, we will examine some studies that relate to the
      doctor-patient relationship in women with CPP.

PMID- 18043576
TI  - Surgical options in the treatment of stress urinary incontinence in women.
AB  - The aim of this review is to provide an update on the surgical options for
      treatment of stress incontinence in women. The efficiency of different procedures
      and the safety associated with each procedure are evaluated, mainly by reviewing
      the randomised controlled trials. The open retropubic colposuspension and the
      sling procedures are the most efficacious for treatment stress urinary
      incontinence especially in the long term. The laparoscopic colposuspension may be
      as good as the open colposuspension, but the long-term performance remains
      uncertain. The newer minimal access vaginal sling procedures appear to offer
      benefits of minimal access surgery with success rate similar to the
      colposuspension and the traditional slings and minor morbidity in the short and
      median-term. However long term data is still awaited. The transobturator
      technique does not seem to provide advantages compared to the classical TVT
      procedure. Urethral injection therapy does not seem to have the same efficacy as
      conventional surgery and long term data is still scanty. However, because of low
      operative morbidity it represents a favourable alternative to standard surgery in
      patients who prefer less invasive treatment, the frail elderly and other selected
      women where conventional surgery is problematic.

PMID- 18043577
TI  - Umbilical Richter's hernia after minimally invasive laparoscopy. A case report.
AB  - A case of Richter's hernia in the umbilical trocar site following laparoscopic
      radiofrequency thermal ablation of uterine myomas is presented. A 10-mm trocar
      was inserted through the umbilical site and the radiofrequency needle was
      introduced percutaneously into the uterine fibroid. Trocar was extracted under
      direct visual control after carbonic gas deflation. The fascial layer of
      umbilical port was not sutured. The umbilical Richter's hernia presented 13 days
      later required bowel resection. This case stresses the importance of suturing the
      fascial defects of 5-mm larger ports also in diagnostic and in minimally invasive
      laparoscopic procedures.

PMID- 18043578
TI  - Immunohistochemical categorisation of ductal carcinoma in situ of the breast.
AB  - The aim of this study is to analyse whether immunohistochemistry (IHC) applying a
      broad set of markers could be used to categorise ductal carcinoma in situ (DCIS)
      of the breast in distinct subgroups corresponding to the recently defined
      molecular categories of invasive carcinoma. Immunohistochemistry of pure DCIS
      cases constructed in tissue arrays was performed with 16 markers (oestrogen
      receptor (ER), progesterone receptor (PR), androgen receptor (AR), Bcl-2, p53,
      Her2, insulin-like growth factor receptor, E-cadherin, epithelial membrane
      antigen (EMA), CA125, keratins 5/6, 14, 19, epidermal growth factor receptor,
      S100, and CD31). Results in 163 cases were analysed by unsupervised hierarchical
      clustering. Histological classification was performed by review of whole tissue
      sections and identified 36 well-, 55 intermediately, and 72 poorly differentiated
      DCISs. Unsupervised hierarchical cluster analysis categorised DCIS into two major
      groups that could be further subdivided into subgroups based on the expression of
      six markers (ER, PR, AR, Bcl-2, p53, and Her2). In the major predominantly ER/Bcl
      2-positive (luminal) group, three subgroups (AR-positive (n=33), AR-negative
      (n=40), and mixed (n=34)) could be identified and included 34 well-differentiated
      DCISs. Within the major predominantly ER/Bcl-2-negative (nonluminal) group, a
      Her2-positive subgroup (n=34) was characterised by 31 poorly differentiated
      lesions. Eight triple-negative lesions, including one positive for keratin 5/6
      and two positive for p53, were encountered. Intermediately differentiated DCIS
      shared a comparable IHC staining pattern with well-differentiated DCIS that was
      distinct from poorly differentiated DCIS (P<0.001). Ductal carcinoma in situ
      could be categorised by IHC into two major groups and five subgroups using six
      markers. Morphologically, intermediately differentiated DCIS seems to have more
      biological similarities with well-differentiated lesions as compared to poorly
      differentiated lesions.

PMID- 18043579
TI  - Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving
      dose-intensive or standard dose chemotherapy for high-risk primary breast cancer.
AB  - Quality of life (QL) is an important consideration when comparing adjuvant
      therapies for early breast cancer, especially if they differ substantially in
      toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose
      intensive epirubicin and cyclophosphamide administered with filgrastim and
      progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy
      (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without
      disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients
      scored QL indicators. Mean durations for the three transition times were weighted
      with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC
      reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but
      a faster recovery 3 months following chemotherapy than patients receiving SD-CT,
      for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer
      for patients receiving DI-EC (95% CI, -2.5 to 6.1). Q-TWiST favoured DI-EC for
      most values of utilities attached to TOX and REL. Despite greater initial
      toxicity, quality-adjusted survival was similar or better with dose-intensive
      treatment as compared to standard treatment. Thus, QL considerations should not
      be prohibitive if future intensive therapies show superior efficacy.

PMID- 18043581
TI  - Keeping protests within the law.

PMID- 18043580
TI  - Identification of Lck-derived peptides applicable to anti-cancer vaccine for
      patients with human leukocyte antigen-A3 supertype alleles.
AB  - The identification of peptide vaccine candidates to date has been focused on
      human leukocyte antigen (HLA)-A2 and -A24 alleles. In this study, we attempted to
      identify cytotoxic T lymphocyte (CTL)-directed Lck-derived peptides applicable to
      HLA-A11(+), -A31(+), or -A33(+) cancer patients, because these HLA-A alleles
      share binding motifs, designated HLA-A3 supertype alleles, and because the Lck is
      preferentially expressed in metastatic cancer. Twenty-one Lck-derived peptides
      were prepared based on the binding motif to the HLA-A3 supertype alleles. They
      were first screened for their recognisability by immunoglobulin G (IgG) in the
      plasma of prostate cancer patients, and the selected candidates were subsequently
      tested for their potential to induce peptide-specific CTLs from peripheral blood
      mononuclear cells of HLA-A3 supertype(+) cancer patients. As a result, four Lck
      peptides were frequently recognised by IgGs, and three of them - Lck(90-99),
      Lck(449-458), and Lck(450-458) - efficiently induced peptide-specific and cancer
      reactive CTLs. Their cytotoxicity towards cancer cells was mainly ascribed to HLA
      class I-restricted and peptide-specific CD8(+) T cells. These results indicate
      that these three Lck peptides are applicable to HLA-A3 supertype(+) cancer
      patients, especially those with metastasis. This information could facilitate the
      development of peptide-based anti-cancer vaccine for patients with alleles other
      than HLA-A2 and -A24.

PMID- 18043583
TI  - Dopamine: at the intersection of reward and action.

PMID- 18043584
TI  - Microgliosis: the questions shape the answers.

PMID- 18043585
TI  - A sharper view from the top.

PMID- 18043586
TI  - The main olfactory bulb and innate behavior: different perspectives on an
      olfactory scene.

PMID- 18043590
TI  - Is duodenal biopsy required in all patients with suspected celiac disease?

PMID- 18043591
TI  - Should clinicians integrate medical and psychological interventions for the
      treatment of functional dyspepsia?

PMID- 18043592
TI  - Screening for chronic kidney disease in patients with diabetes: are we missing
      the point?

PMID- 18043593
TI  - Urine neutrophil gelatinase-associated lipocalin as a marker of acute kidney
      injury in critically ill children.

PMID- 18043594
TI  - Outcome in childhood cerebral venous thrombosis--new insights.

PMID- 18043595
TI  - Long-term left-ventricular-assist-device therapy is here to stay.

PMID- 18043596
TI  - Pediatric rheumatic heart disease in the developing world: echocardiographic
      versus clinical screening.

PMID- 18043597
TI  - New percutaneous mechanical left ventricular support for acute MI: the AMC MACH
      program.

PMID- 18043598
TI  - Should aspirin be used as a preventive therapy for thrombosis in patients with
      antiphospholipid antibodies?

PMID- 18043599
TI  - Emerging viral infections and arthritis: the role of the rheumatologist.

PMID- 18043600
TI  - Should patients with RA be aggressively monitored for hypertension?

PMID- 18043601
TI  - Low-risk prostate cancer can and should often be managed with active surveillance
      and selective delayed intervention.

PMID- 18043602
TI  - Are metastatic testicular tumors curable with high-dose chemotherapy and stem
      cell rescue?

PMID- 18043603
TI  - Cisplatin alone or in combination versus hydroxyurea during pelvic irradiation
      for cervical cancer.

PMID- 18043604
TI  - Adjuvant use of interferon alpha 2b is not justified in patients with stage
      IIb/III melanoma.

PMID- 18043605
TI  - Physical fitness in childhood and adolescence: a powerful marker of health.
AB  - This review aims to summarize the latest developments with regard to physical
      fitness and several health outcomes in young people. The literature reviewed
      suggests that (1) cardiorespiratory fitness levels are associated with total and
      abdominal adiposity; (2) both cardiorespiratory and muscular fitness are shown to
      be associated with established and emerging cardiovascular disease risk factors;
      (3) improvements in muscular fitness and speed/agility, rather than
      cardiorespiratory fitness, seem to have a positive effect on skeletal health; (4)
      both cardiorespiratory and muscular fitness enhancements are recommended in
      pediatric cancer patients/survivors in order to attenuate fatigue and improve
      their quality of life; and (5) improvements in cardiorespiratory fitness have
      positive effects on depression, anxiety, mood status and self-esteem, and seem
      also to be associated with a higher academic performance. In conclusion, health
      promotion policies and physical activity programs should be designed to improve
      cardiorespiratory fitness, but also two other physical fitness components such us
      muscular fitness and speed/agility. Schools may play an important role by
      identifying children with low physical fitness and by promoting positive health
      behaviors such as encouraging children to be active, with special emphasis on the
      intensity of the activity.

PMID- 18043606
TI  - The ISME journal: multidisciplinary journal of microbial ecology.

PMID- 18043607
TI  - The ISME journal: a major milestone for the International Society for Microbial
      Ecology and the microbial ecology community.

PMID- 18043608
TI  - Microbial ecology and environmental biotechnology.

PMID- 18043609
TI  - Microbial ecology meets electrochemistry: electricity-driven and driving
      communities.
AB  - Bio-electrochemical systems (BESs) have recently emerged as an exciting
      technology. In a BES, bacteria interact with electrodes using electrons, which
      are either removed or supplied through an electrical circuit. The most-described
      type of BES is microbial fuel cells (MFCs), in which useful power is generated
      from electron donors as, for example, present in wastewater. This form of charge
      transport, known as extracellular electron transfer, was previously extensively
      described with respect to metals such as iron and manganese. The importance of
      these interactions in global biogeochemical cycles is essentially undisputed. A
      wide variety of bacteria can participate in extracellular electron transfer, and
      this phenomenon is far more widespread than previously thought. The use of BESs
      in diverse research projects is helping elucidate the mechanism by which bacteria
      shuttle electrons externally. New forms of interactions between bacteria have
      been discovered demonstrating how multiple populations within microbial
      communities can co-operate to achieve energy generation. New environmental
      processes that were difficult to observe or study previously can now be simulated
      and improved via BESs. Whereas pure culture studies make up the majority of the
      studies performed thus far, even greater contributions of BESs are expected to
      occur in natural environments and with mixed microbial communities. Owing to
      their versatility, unmatched level of control and capacity to sustain novel
      processes, BESs might well serve as the foundation of a new environmental
      biotechnology. While highlighting some of the major breakthroughs and addressing
      only recently obtained data, this review points out that despite rapid progress,
      many questions remain unanswered.

PMID- 18043610
TI  - New processes and players in the nitrogen cycle: the microbial ecology of
      anaerobic and archaeal ammonia oxidation.
AB  - Microbial activities drive the global nitrogen cycle, and in the past few years,
      our understanding of nitrogen cycling processes and the micro-organisms that
      mediate them has changed dramatically. During this time, the processes of
      anaerobic ammonium oxidation (anammox), and ammonia oxidation within the domain
      Archaea, have been recognized as two new links in the global nitrogen cycle. All
      available evidence indicates that these processes and organisms are critically
      important in the environment, and particularly in the ocean. Here we review what
      is currently known about the microbial ecology of anaerobic and archaeal ammonia
      oxidation, highlight relevant unknowns and discuss the implications of these
      discoveries for the global nitrogen and carbon cycles.

PMID- 18043611
TI  - Microbial ecology of biological invasions.
AB  - Invasive microbes, plants and animals are a major threat to the composition and
      functioning of ecosystems; however, the mechanistic basis of why exotic species
      can be so abundant and disruptive is not well understood. Most studies have
      focused on invasive plants and animals, although few have considered the effects
      of invasive microbes, or interactions of invasive plant and animal species with
      microbial communities. Here, we review effects of invasive plants on soil
      microbial communities and discuss consequences for plant performance, plant
      community structure and ecosystem processes. In addition, we briefly discuss
      effects of invasive soil microbes on plant communities, which has been less well
      studied, and effects of invasive animals on soil decomposers and ecosystem
      functioning. We do this by considering each of three important functional groups
      of microbes, namely soil microbial parasites and pathogens, mutualistic symbionts
      and decomposers. We conclude that invasive plants, pathogenic and symbiotic soil
      microbes will have strongest effects on the abundance of individual species,
      community diversity and ecosystem functioning. Invasive decomposer microbes
      probably have little impact, because of limited specificity and great functional
      redundancy. However, invasive plants and animals can have major effects on
      microbial decomposition in soil. We propose that understanding, predicting and
      counteracting consequences of enhanced global homogenization of natural
      communities through introducing exotic plants, animals and microbes will require
      future studies on how pathogenic, symbiotic and decomposer soil microbes
      interact, how they are influenced by higher trophic level organisms and how their
      combined effects are influencing the composition and functioning of ecosystems.

PMID- 18043612
TI  - Synchrony in aquatic microbial community dynamics.
AB  - Population dynamics are influenced by drivers acting from outside and from within
      an ecosystem. Extrinsic forces operating over broad spatial scales can impart
      synchronous behavior to separate populations, while internal, system-specific
      drivers often lead to idiosyncratic behavior. Here, we demonstrate synchrony in
      community-level dynamics among phytoplankton and bacteria in six north temperate
      humic lakes. The influence of regional meteorological factors explained much of
      the temporal variability in the phytoplankton community, and resulted in
      synchronous patterns of community change among lakes. Bacterial dynamics, in
      contrast, were driven by system-specific interactions with phytoplankton. Despite
      the importance of intrinsic factors for determining bacterial community
      composition and dynamics, we demonstrated that biological interactions
      transmitted the signal of the regional extrinsic drivers to the bacterial
      communities, ultimately resulting in synchronous community phenologies for
      bacterioplankton communities as well. This demonstrates how linkages between the
      components of a complex biological system can work to simplify the dynamics of
      the system and implies that it may be possible to predict the behavior of
      microbial communities responsible for important biogeochemical services in the
      landscape.

PMID- 18043613
TI  - Adaptation and spectral tuning in divergent marine proteorhodopsins from the
      eastern Mediterranean and the Sargasso Seas.
AB  - Proteorhodopsins (PRs) phototrophy was recently discovered in oceanic surface
      waters. PRs have been observed in different marine environments and in diverse
      taxa, including the ubiquitous marine alphaproteobacterial SAR11 group and the
      uncultured gammaproteobacterial SAR86 group. Previously, two SAR86 PR subgroups,
      discovered in the Pacific Ocean, were shown to absorb light with different
      maxima, lambda max 527 nm (green) and lambda max 490 nm (blue) and their
      distribution was explained by prevailing light conditions - green pigments at the
      surface and blue in deeper waters. Here, we show that PRs display high diversity
      in geographically distinct patterns despite similar physical water column
      properties such as mixing and light penetration. We compared summer and winter
      samples representing stratified and mixed conditions from both the Mediterranean
      and Sargasso Sea. As expected, in the Mediterranean Sea, green pigments were
      mainly confined to the surface and the percentage of blue pigments increased
      toward deeper samples; in the Sargasso Sea, unexpectedly, all PRs were of the
      blue type. As an additional result, both locations show seasonal dependence in
      the distribution of different PR families. Finally, spectral tuning was not
      restricted to a single PR family as previously reported but occurs across the
      sampled PR families from various microbial taxa. The distribution of tunable PRs
      across the PR tree suggests that ready adaptability has been distributed widely
      among microorganisms, and may be a reason that PRs are abundant and taxonomically
      widely dispersed.

PMID- 18043614
TI  - Long-term ecological impacts of antibiotic administration on the human intestinal
      microbiota.
AB  - Antibiotic administration is known to cause short-term disturbances in the
      microbiota of the human gastrointestinal tract, but the potential long-term
      consequences have not been well studied. The aims of this study were to analyse
      the long-term impact of a 7-day clindamycin treatment on the faecal microbiota
      and to simultaneously monitor the ecological stability of the microbiota in a
      control group as a baseline for reference. Faecal samples from four clindamycin
      exposed and four control subjects were collected at nine different time points
      over 2 years. Using a polyphasic approach, we observed highly significant
      disturbances in the bacterial community that persisted throughout the sampling
      period. In particular, a sharp decline in the clonal diversity of Bacteroides
      isolates, as assessed by repetitive sequence-based PCR (rep-PCR) and long-term
      persistence of highly resistant clones were found as a direct response to the
      antibiotic exposure. The Bacteroides community never returned to its original
      composition during the study period as assessed using the molecular
      fingerprinting technique, terminal restriction fragment length polymorphism (T
      RFLP). Furthermore, using real-time PCR we found a dramatic and persistent
      increase in levels of specific resistance genes in DNA extracted from the faeces
      after clindamycin administration. The temporal variations in the microbiota of
      the control group were minor compared to the large and persistent shift seen in
      the exposed group. These results demonstrate that long after the selection
      pressure from a short antibiotic exposure has been removed, there are still
      persistent long term impacts on the human intestinal microbiota that remain for
      up to 2 years post-treatment.

PMID- 18043615
TI  - GeoChip: a comprehensive microarray for investigating biogeochemical, ecological
      and environmental processes.
AB  - Owing to their vast diversity and as-yet uncultivated status, detection,
      characterization and quantification of microorganisms in natural settings are
      very challenging, and linking microbial diversity to ecosystem processes and
      functions is even more difficult. Microarray-based genomic technology for
      detecting functional genes and processes has a great promise of overcoming such
      obstacles. Here, a novel comprehensive microarray, termed GeoChip, has been
      developed, containing 24,243 oligonucleotide (50 mer) probes and covering >10,000
      genes in >150 functional groups involved in nitrogen, carbon, sulfur and
      phosphorus cycling, metal reduction and resistance, and organic contaminant
      degradation. The developed GeoChip was successfully used for tracking the
      dynamics of metal-reducing bacteria and associated communities for an in situ
      bioremediation study. This is the first comprehensive microarray currently
      available for studying biogeochemical processes and functional activities of
      microbial communities important to human health, agriculture, energy, global
      climate change, ecosystem management, and environmental cleanup and restoration.
      It is particularly useful for providing direct linkages of microbial
      genes/populations to ecosystem processes and functions.

PMID- 18043616
TI  - Diazotrophic bacterioplankton in a coral reef lagoon: phylogeny, diel nitrogenase
      expression and response to phosphate enrichment.
AB  - We investigated diazotrophic bacterioplankton assemblage composition in the Heron
      Reef lagoon (Great Barrier Reef, Australia) using culture-independent techniques
      targeting the nifH fragment of the nitrogenase gene. Seawater was collected at 3
      h intervals over a period of 72 h (i.e. over diel as well as tidal cycles). An
      incubation experiment was also conducted to assess the impact of phosphate
      (PO(4)3*) availability on nifH expression patterns. DNA-based nifH libraries
      contained primarily sequences that were most similar to nifH from sediment,
      microbial mat and surface-associated microorganisms, with a few sequences that
      clustered with typical open ocean phylotypes. In contrast to genomic DNA
      sequences, libraries prepared from gene transcripts (mRNA amplified by reverse
      transcription-polymerase chain reaction) were entirely cyanobacterial and
      contained phylotypes similar to those observed in open ocean plankton. The
      abundance of Trichodesmium and two uncultured cyanobacterial phylotypes from
      previous studies (group A and group B) were studied by quantitative-polymerase
      chain reaction in the lagoon samples. These were detected as transcripts, but
      were not detected in genomic DNA. The gene transcript abundance of these
      phylotypes demonstrated variability over several diel cycles. The PO(4)3*
      enrichment experiment had a clearer pattern of gene expression over diel cycles
      than the lagoon sampling, however PO(4)3* additions did not result in enhanced
      transcript abundance relative to control incubations. The results suggest that a
      number of diazotrophs in bacterioplankton of the reef lagoon may originate from
      sediment, coral or beachrock surfaces, sloughing into plankton with the flooding
      tide. The presence of typical open ocean phylotype transcripts in lagoon
      bacterioplankton may indicate that they are an important component of the N cycle
      of the coral reef.

PMID- 18043617
TI  - Frequency-dependent advantages of plasmid carriage by Pseudomonas in homogeneous
      and spatially structured environments.
AB  - The conditions promoting the persistence of a plasmid carrying a trait that may
      be mutually beneficial to other cells in its vicinity were studied in structured
      and unstructured environments. A large plasmid encoding mercury resistance in
      Pseudomonas fluorescens was used, and the mercury concentration allowing invasion
      from rare for both plasmid-bearing and plasmid-free cells was determined for
      different initial inoculum densities in batch-culture structured (filter surface)
      and unstructured (mixed broth) environments. A range of mercury concentrations
      were found where both cell types could coexist, the regions being relatively
      similar in the two types of environment although density-dependent in the
      unstructured environment. The coexistence is explained in terms of frequency
      dependent selection of the mutually beneficial mercury resistance trait, and the
      dynamics of bacterial growth under batch culture conditions. However, the region
      of coexistence was complicated by conjugation which increased plasmid spread in
      the mixed broth culture but not the structured environment.

PMID- 18043618
TI  - Culture clash: challenging the dogma of microbial diversity.

PMID- 18043619
TI  - What's the 'meta' with metagenomics?

PMID- 18043620
TI  - Who eats what, where and when? Isotope-labelling experiments are coming of age.
AB  - Isotope-labelling experiments have changed the way microbial ecologists
      investigate the ecophysiology of microbial populations and cells in the
      environment. Insight into the 'uncultivated majority' accompanies methodology
      that involves the incorporation of stable isotopes or radioisotopes into sub
      populations of environmental samples. Subsequent analysis of labelled biomarkers
      of sub-populations with stable-isotope probing (DNA-SIP, RNA-SIP, phospholipid
      derived fatty acid-SIP) or individual cells with a combination of fluorescence in
      situ hybridization and microautoradiography reveals linked phylogenetic and
      functional information about the organisms that assimilated these compounds.
      Here, we review some of the most recent literature, with an emphasis on
      methodological improvements to the sensitivity and utility of these methods. We
      also highlight related isotope techniques that are in continued development and
      hold promise to transform the way we link phylogeny and function in complex
      microbial communities.

PMID- 18043621
TI  - Recovery in culture of viable but nonculturable Vibrio parahaemolyticus: regrowth
      or resuscitation?
AB  - The objective of this study was to explore the recovery of culturability of
      viable but nonculturable (VBNC) Vibrio parahaemolyticus after temperature upshift
      and to determine whether regrowth or resuscitation occurred. A clinical strain of
      V. parahaemolyticus Vp5 was rendered VBNC by exposure to artificial seawater
      (ASW) at 4 degrees C. Aliquots of the ASW suspension of cells (0.1, 1 and 10 ml)
      were subjected to increased temperatures of 20 degrees C and 37 degrees C.
      Culturability of the cells in the aliquots was monitored for colony formation on
      a rich medium and changes in morphology were measured by scanning (SEM) and
      transmission (TEM) electron microscopy. Samples of VBNC cells were fixed and
      examined by SEM, revealing a heterogeneous population comprising small cells and
      larger, flattened cells. Forty-eight hours after temperature upshift to 20
      degrees C or 37 degrees C, both elongation and division by binary fission of the
      cells were observed, employing SEM and TEM, but only in the 10-ml aliquots. The
      results suggest that a portion of VBNC cells is able to undergo cell division. It
      is concluded that a portion of VBNC cells of V. parahaemolyticus subjected to
      cold temperatures remain viable. After temperature upshift, regrowth of those
      cells, rather than resuscitation of all bacteria of the initial inoculum, appears
      to be responsible for recovery of culturability of VBNC cells of V.
      parahaemolyticus. Nutrient in filtrates of VBNC cells is hypothesized to allow
      growth of the temperature-responsive cells, with cell division occurring via
      binary fission, but also including an atypical, asymmetric cell division.

PMID- 18043622
TI  - Differences in the composition of vaginal microbial communities found in healthy
      Caucasian and black women.
AB  - The maintenance of a low pH in the vagina through the microbial production of
      lactic acid is known to be an important defense against infectious disease in
      reproductive age women. Previous studies have shown that this is largely
      accomplished through the metabolism of lactic acid bacteria, primarily species of
      Lactobacillus. Despite the importance of this defense mechanism to women's
      health, differences in the species composition of vaginal bacterial communities
      among women have not been well defined, nor is it known if and how these
      differences might be linked to differences in the risk of infection. In this
      study, we defined and compared the species composition of vaginal bacterial
      communities in 144 Caucasian and black women in North America. This was carried
      out based on the profiles of terminal restriction fragments of 16S rRNA genes,
      and phylogenetic analysis of 16S rRNA gene sequences of the numerically dominant
      microbial populations. Among all the women sampled, there were eight major kinds
      of vaginal communities ('supergroups') that occurred in the general populace at a
      frequency of at least 0.05 (P=0.99). From the distribution of these supergroups
      among women, it was possible to draw several conclusions. First, there were
      striking, statistically significant differences (P=0.0) in the rank abundance of
      community types among women in these racial groups. Second, the incidence of
      vaginal communities in which lactobacilli were not dominant was higher in black
      women (33%) as compared to Caucasian women (7%). Communities not dominated by
      lactobacilli had Atopobium and a diverse array of phylotypes from the order
      Clostridiales. Third, communities dominated by roughly equal numbers of more than
      one species of Lactobacillus were rare in black women, but common in Caucasian
      women. We postulate that because of these differences in composition, not all
      vaginal communities are equally resilient, and that differences in the vaginal
      microbiota of Caucasian and black women may at least partly account for known
      disparities in the susceptibility of women in these racial groups to bacterial
      vaginosis and sexually transmitted diseases.

PMID- 18043624
TI  - Honey and royal jelly, like human milk, abrogate lectin-dependent infection
      preceding Pseudomonas aeruginosa adhesion.
AB  - Pseudomonas aeruginosa antibiotic resistance has led to the search of natural
      compounds, which would competitively block its fucose>fructose/mannose-binding
      lectin (PA-IIL) that mediates its biofilm formation and adhesion to animal cells.
      Such compounds were found in human milk (HM) and avian egg whites. The present
      research has revealed that honey and royal jelly (RJ), which are assigned to
      protect beehive progeny and are applied for human infection therapy, match HM in
      PA-IIL blocking. The function of their fructose (higher in honey) and
      mannosylated glycoproteins (higher in RJ) as powerful decoys in PA-IIL
      neutralization is of ecological/biological importance and implementability for
      the antibacterial adhesion therapeutic strategy.

PMID- 18043623
TI  - Biphenyl-utilizing bacteria and their functional genes in a pine root zone
      contaminated with polychlorinated biphenyls (PCBs).
AB  - Bacteria and functional genes associated with biphenyl (BP) degradation in the
      root zone of an Austrian pine (Pinus nigra L.) growing naturally in
      polychlorinated-BP (PCB)-contaminated soil were identified using stable isotope
      probing (SIP) integrated with comprehensive functional gene analyses. SIP
      revealed 75 different genera that derived carbon from 13C-BP, with
      Pseudonocardia, Kribella, Nocardiodes and Sphingomonas predominating carbon
      acquisition. Rhodococcus spp. were not detected with SIP, despite being the most
      abundant BP utilizers isolated from agar plates. Only one organism, an
      Arthrobacter spp., was detected as a BP utilizer by both cultivation and SIP
      methods. Time-course SIP analyses indicated that secondary carbon flow from BP
      utilizing bacteria into other soil organisms may have occurred largely between 4
      and 14 days incubation. Functional gene contents of the BP-utilizing metagenome
      (13C-DNA) were explored using the GeoChip, a functional gene array containing
      6465 probes targeting aromatic degradative genes. The GeoChip detected 27 genes,
      including several associated with catabolism of BP, benzoate and a variety of
      aromatic ring hydroxylating dioygenase (ARHD) subunits. Genes associated with the
      beta-ketoadipate pathway were also detected, suggesting a potential role for this
      plant aromatic catabolic pathway in PCB degradation. Further ARHD analyses using
      targeted polymerase chain reaction primers and sequence analyses revealed novel
      dioxygenase sequences in 13C-DNA, including several sequences that clustered
      distantly from all known ARHDs and others that resembled known Rhodococcus ARHDs.
      The findings improve our understanding of BP degradation and carbon flow in soil,
      reveal the extent of culture bias, and may benefit bioremediation research by
      facilitating the development of molecular tools to detect, quantify and monitor
      populations involved in degradative processes.

PMID- 18043625
TI  - Inter-species transplantation of gut microbiota from human to pigs.
AB  - Direct research on gut microbiota for understanding its role as 'an important
      organ' in human individuals is difficult owing to its vast diversity and host
      specificity as well as ethical concerns. Transplantation of human gut microbiota
      into surrogate hosts can significantly facilitate the research of human gut
      ecology, metabolism and immunity but rodents-based model provides results with
      low relevance to humans. A new human flora-associated (HFA) piglet model was
      hereby established taking advantage of the high similarity between pigs and
      humans with respect to the anatomy, physiology and metabolism of the digestive
      system. Piglets were delivered via cesarean section into a SPF-level barrier
      system and were inoculated orally with a whole fecal suspension from one healthy
      10-year-old boy. The establishment and composition of the intestinal microbiota
      of the HFA piglets were analyzed and compared with that of the human donor using
      enterobacterial repetitive intergenic consensus sequence-PCR fingerprinting-based
      community DNA hybridization, group-specific PCR-temperature gradient gel
      electrophoresis and real-time PCR. Molecular profiling demonstrated that
      transplantation of gut microbiota from a human to germfree piglets produced a
      donor-like microbial community with minimal individual variation. And the
      microbial succession with aging of those ex-germfree piglets was also similar to
      that observed in humans. This HFA model provides a significantly improved system
      for research on gut ecology in human metabolism, nutrition and drug discovery.

PMID- 18043626
TI  - Functional microarray analysis of nitrogen and carbon cycling genes across an
      Antarctic latitudinal transect.
AB  - Soil-borne microbial communities were examined via a functional gene microarray
      approach across a southern polar latitudinal gradient to gain insight into the
      environmental factors steering soil N- and C-cycling in terrestrial Antarctic
      ecosystems. The abundance and diversity of functional gene families were studied
      for soil-borne microbial communities inhabiting a range of environments from 51
      degrees S (cool temperate-Falkland Islands) to 72 degrees S (cold rock desert
      Coal Nunatak). The recently designed functional gene array used contains 24,243
      oligonucleotide probes and covers >10,000 genes in >150 functional groups
      involved in nitrogen, carbon, sulfur and phosphorus cycling, metal reduction and
      resistance and organic contaminant degradation (He et al. 2007). The detected N-
      and C-cycle genes were significantly different across different sampling
      locations and vegetation types. A number of significant trends were observed
      regarding the distribution of key gene families across the environments examined.
      For example, the relative detection of cellulose degradation genes was correlated
      with temperature, and microbial C-fixation genes were more present in plots
      principally lacking vegetation. With respect to the N-cycle, denitrification
      genes were linked to higher soil temperatures, and N2-fixation genes were linked
      to plots mainly vegetated by lichens. These microarray-based results were
      confirmed for a number of gene families using specific real-time PCR, enzymatic
      assays and process rate measurements. The results presented demonstrate the
      utility of an integrated functional gene microarray approach in detecting shifts
      in functional community properties in environmental samples and provide insight
      into the forces driving important processes of terrestrial Antarctic nutrient
      cycling.

PMID- 18043627
TI  - Parenteral long-acting amoxicillin reduces intestinal bacterial community
      diversity in piglets even 5 weeks after the administration.
AB  - We investigated the long-term effects of a single intramuscular administration of
      amoxicillin (15 mg kg(-1)) 1 day after birth, on piglet intestinal microbiota.
      Animals received no creep feed before weaning on day 28 of age. For the next 11
      days, the piglets received a wheat-barley-based diet. Colon digesta samples were
      collected on day 39 and subjected to denaturing gradient gel electrophoresis
      (DGGE) of PCR-amplified 16S rRNA gene fragments. DGGE fingerprint diversity
      indices differed between the group treated with amoxicillin and the untreated
      group (0.8+/-0.19 and 1.03+/-0.17, respectively, P=0.012). Reamplification and
      sequencing of two bands present in all samples revealed that a Roseburia faecalis
      related population was strongly reduced in relative abundance (98% identity) in
      the treated group, while an enterobacterial population with 100% identity to
      Shigella spp., Escherichia coli and Salmonella enterica serovar Typhi was
      enriched. A band corresponding to Lactobacillus sobrius was present only in the
      control group. The protective effect of prophylactic antibiotic administration
      may be outweighed by the long-lasting disturbance of the gut ecosystem.

PMID- 18043628
TI  - Metagenomics and the global ocean survey: what's in it for us, and why should we
      care?

PMID- 18043629
TI  - Soaking it up: the complex lives of marine sponges and their microbial
      associates.

PMID- 18043630
TI  - The effects of subtherapeutic antibiotic use in farm animals on the proliferation
      and persistence of antibiotic resistance among soil bacteria.
AB  - The use of antibiotics at subtherapeutic concentrations for agricultural
      applications is believed to be an important factor in the proliferation of
      antibiotic-resistant bacteria. The goal of this study was to determine if the
      application of manure onto agricultural land would result in the proliferation of
      antibiotic resistance among soil bacteria. Chlortetracycline-resistant bacteria
      were enumerated and characterized from soils exposed to the manure of animals fed
      subtherapeutic concentrations of antibiotics and compared to the
      chlortetracycline-resistant bacteria from soils at farms with restricted
      antibiotic use (dairy farms) and from non-agricultural soils. No significant
      differences were observed at nine different study sites with respect to the
      numbers and types of cultivated chlortetracycline-resistant bacteria. Genes
      encoding for tetracycline resistance were rarely detected in the resistant
      bacteria from these sites. In contrast, soils collected from a tenth farm, which
      allowed manure to indiscriminately accumulate outside the animal pen, had
      significantly higher chlortetracycline-resistance levels. These resistant
      bacteria frequently harbored one of 14 different genes encoding for tetracycline
      resistance, many of which (especially tet(A) and tet(L)) were detected in
      numerous different bacterial species. Subsequent bacterial enumerations at this
      site, following the cessation of farming activity, suggested that this farm
      remained a hotspot for antibiotic resistance. In conclusion, we speculate that
      excessive application of animal manure leads to the spread of resistance to soil
      bacteria (potentially by lateral gene transfer), which then serve as persistent
      reservoir of antibiotic resistance.

PMID- 18043631
TI  - Survival of genetically marked Escherichia coli O157:H7 in soil as affected by
      soil microbial community shifts.
AB  - A loamy sand soil sampled from a species-rich permanent grassland at a long-term
      experimental site (Wildekamp, Bennekom, The Netherlands) was used to construct
      soil microcosms in which the microbial community compositions had been modified
      by fumigation at different intensities (depths). As expected, increasing depth of
      fumigation was shown to result in progressively increasing effects on the
      microbiological soil parameters, as determined by cultivation-based as well as
      cultivation-independent (PCR-DGGE, PLFA) methods. Both at 7 and at 60 days after
      fumigation, shifts in the bacterial, fungal and protozoan communities were noted,
      indicating that altered community compositions had emerged following a transition
      phase. At the level of bacteria culturable on plates, an increase of the
      prevalence of bacterial r-strategists was noted at 7 days followed by a decline
      at 60 days, which also hinted at the effectiveness of the fumigation treatments.
      The survival of a non-toxigenic Escherichia coli O157:H7 derivative, strain T,
      was then assessed over 60 days in these microcosms, using detection via colony
      forming units counts as well as via PCR-DGGE. Both data sets were consistent with
      each other. Thus, a clear effect of fumigation depth on the survival of the
      invading strain T was noted, as a progressive increase of depth coincided with a
      progressively enhanced inoculant survival rate. As fumigation depth was
      presumably inversely related to community complexity, this was consistent with
      the hypothesis that soil systems with reduced biological complexity offer
      enhanced opportunities for invading microbial species to establish and persist.
      The significance of this finding is discussed in the light of the ongoing
      discussion about the complexity-invasiveness relationship within microbial
      communities, in particular regarding the opportunities of pathogens to persist.

PMID- 18043632
TI  - The introduction of genetically modified microorganisms designed for
      rhizoremediation induces changes on native bacteria in the rhizosphere but not in
      the surrounding soil.
AB  - A 168-day microcosms experiment was used to assess the possible functional and
      structural shifts occurring in the bacterial community of a site with a
      historical record of polychlorinated biphenyl (PCB) contamination, after the
      introduction of plants whose roots have been inoculated with genetically modified
      (GM) microorganisms, designed for rhizoremediation. Salix sp. plants were
      inoculated with two different GM Pseudomonas fluorescens strains or with their
      parental wild-type strain. Both bulk soil and rhizosphere samples were analyzed.
      Physiological profiles based on 31 ecologically relevant carbon sources were used
      to detect differences in bacterial community functions. The community structure
      of eubacteria, alpha and beta-proteobacteria, actinobacteria and acidobacteria
      communities were analyzed via a polymerase chain reaction-thermal gradient gel
      electrophoresis (TGGE) approach. The introduced transgenes had no effect on the
      function and structure of the bacterial community in bulk soil, although they
      enhanced biodegradation of PCBs as determined by chemical analysis. However, the
      transgenes effected the development of functionally and genetically distinct
      bacterial communities in the rhizosphere. Moreover, structural and functional
      differences were detected between planted and unplanted soils and between soil
      and rhizosphere samples. In the case of the different group-specific structures
      studied, differences were observed between groups because of time-dependant
      shifts, rhizosphere effect and bacterial strain introduced.

PMID- 18043633
TI  - Functional metaproteome analysis of protein extracts from contaminated soil and
      groundwater.
AB  - Using proteins from soil or groundwater as functional biomarkers requires
      efficient extraction. We developed an extraction method in which the separation
      of proteins from the inorganic and organic constituents of the soil matrix was
      achieved by a combination of 0.1 M NaOH treatment and phenol extraction.
      Incubation with NaOH released humic acids and proteins from soil minerals, and
      simultaneously, disrupted microorganisms. The subsequent phenol extraction
      separated the proteins from the humic organic matter. Protein extracts were
      applied to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      and 2D-electrophoresis (2-DE). Spots and bands were excised and individual
      proteins identified by liquid chromatography online linked to mass spectrometry
      (MS) via electrospray ionization source (LC-ESI-MS). To assess the suitability of
      the method for the functional analysis of environmental metaproteomes, it was
      applied to soil that had been enriched in chlorophenoxy acid-degrading bacteria
      by incubation with 2,4-dichlorophenoxy acetic acid (2,4-D) for 22 days. The
      method was also used to analyze groundwater from the aquifer of a chlorobenzene
      contaminated site. The identification of enzymes such as chlorocatechol
      dioxygenases was consistent with bacterial metabolic pathways expected to be
      expressed in these samples. The protocol enabled thus the analysis of the
      metaproteome of soil and groundwater samples. It thereby provides a means to
      study the diversity of environmental microbial communities while addressing
      functional aspects more directly than metagenome or even metatranscriptome
      analysis.

PMID- 18043634
TI  - Genomic plasticity in prokaryotes: the case of the square haloarchaeon.
AB  - The variability in genome content among closely related strains of prokaryotes
      has been one of the most remarkable discoveries of genomics. One way to approach
      the description of this so-called pan-genome is to compare one reference strain
      genome with metagenomic sequences from the environment. We have applied this
      approach to one extreme aquatic habitat, saturated brines in a solar saltern. The
      genome of Haloquadratum walsbyi strain DSM 16790 was compared to an environmental
      metagenome obtained from the exact site of its isolation. This approach revealed
      that some regions of the strain genome were scarcely represented in the
      metagenome. Here we have analyzed these genomic islands (GI) in the genome of DSM
      16790 and compared them with the complete sequence of some fosmids from the
      environmental library. Two of the islands, GI 2 and GI 4, overlapped with two
      large guanine and cytosine (GC)-rich regions that showed evidence of high
      variability through mobile elements. GI 3 seemed to be a phage or phage-remnant
      acquired by the reference genome, but not present in most environmental lineages.
      Most differential gene content was related to small molecule transport and
      detection, probably reflecting adaptation to different pools of organic
      nutrients. GI 1 did not possess traces of mobile elements and had normal GC
      content. This island contained the main cluster of cell envelope glycoproteins
      and the variability found was different from the other GIs. Rather than
      containing different genes it consisted of homologs with low similarity. This
      variation might reflect a phage evasion strategy.

PMID- 18043635
TI  - Characterization of filamentous bacteria, belonging to candidate phylum KSB3,
      that are associated with bulking in methanogenic granular sludges.
AB  - A fatal bulking phenomenon was found to occur occasionally in the methanogenic
      granular sludge of a mesophilic (35-40 degrees C), full-scale upflow anaerobic
      sludge blanket (UASB) reactor treating organic wastewater discharged from a sugar
      manufacturing factory. A vast number of filamentous cells were observed in the
      bulking sludge that were morphologically distinct from the previously recognized
      anaerobic bulking agent Anaerolinea thermophila. 16S rRNA gene-based analyses of
      the microbial populations in the bulking sludge revealed that the dominant
      filamentous organisms were members of proposed candidate bacterial phylum, KSB3.
      Fluorescence in situ hybridization (FISH) analysis of the healthy sludge granules
      showed that the KSB3 filaments were the dominant granule surface population
      suggesting that they are fundamental constituents of the sludge granules and that
      they occasionally overgrow in the reactor, possibly triggering the filamentous
      bulking. We surveyed 10 additional mesophilic and thermophilic anaerobic sludges
      for the presence and diversity of KSB3 populations. Bacteria closely related to
      the characterized KSB3 filaments were present in two types of mesophilically
      grown UASB sludge granules treating actual wastewater discharged from sugar
      processing industries.

PMID- 18043636
TI  - Public computer surfaces are reservoirs for methicillin-resistant staphylococci.
AB  - The role of computer keyboards used by students of a metropolitan university as
      reservoirs of antibiotic-resistant staphylococci was determined. Putative
      methicillin (oxacillin)-resistant staphylococci isolates were identified from
      keyboard swabs following a combination of biochemical and genetic analyses. Of 24
      keyboards surveyed, 17 were contaminated with staphylococci that grew in the
      presence of oxacillin (2 mg l(-1)). Methicillin (oxacillin)-resistant
      Staphylococcus aureus (MRSA), -S. epidermidis (MRSE) and -S. hominis (MRSH) were
      present on two, five and two keyboards, respectively, while all three
      staphylococci co-contaminated one keyboard. Furthermore, these were found to be
      part of a greater community of oxacillin-resistant bacteria. Combined with the
      broad user base common to public computers, the presence of antibiotic-resistant
      staphylococci on keyboard surfaces might impact the transmission and prevalence
      of pathogens throughout the community.

PMID- 18043637
TI  - Witnessing the last supper of uncultivated microbial cells with Raman-FISH.

PMID- 18043638
TI  - Colorful niches of phototrophic microorganisms shaped by vibrations of the water
      molecule.
AB  - The photosynthetic pigments of phototrophic microorganisms cover different
      regions of the solar light spectrum. Utilization of the light spectrum can be
      interpreted in terms of classical niche theory, as the light spectrum offers
      opportunities for niche differentiation and allows coexistence of species
      absorbing different colors of light. However, which spectral niches are available
      for phototrophic microorganisms? Here, we show that the answer is hidden in the
      vibrations of the water molecule. Water molecules absorb light at specific
      wavebands that match the energy required for their stretching and bending
      vibrations. Although light absorption at these specific wavelengths appears only
      as subtle shoulders in the absorption spectrum of pure water, these subtle
      shoulders create large gaps in the underwater light spectrum due to the
      exponential nature of light attenuation. Model calculations show that the
      wavebands between these gaps define a series of distinct niches in the underwater
      light spectrum. Strikingly, these distinct spectral niches match the light
      absorption spectra of the major photosynthetic pigments on our planet. This
      suggests that vibrations of the water molecule have played a major role in the
      ecology and evolution of phototrophic microorganisms.

PMID- 18043639
TI  - Pyrosequencing enumerates and contrasts soil microbial diversity.
AB  - Estimates of the number of species of bacteria per gram of soil vary between 2000
      and 8.3 million (Gans et al., 2005; Schloss and Handelsman, 2006). The highest
      estimate suggests that the number may be so large as to be impractical to test by
      amplification and sequencing of the highly conserved 16S rRNA gene from soil DNA
      (Gans et al., 2005). Here we present the use of high throughput DNA
      pyrosequencing and statistical inference to assess bacterial diversity in four
      soils across a large transect of the western hemisphere. The number of bacterial
      16S rRNA sequences obtained from each site varied from 26,140 to 53,533. The most
      abundant bacterial groups in all four soils were the Bacteroidetes,
      Betaproteobacteria and Alphaproteobacteria. Using three estimators of diversity,
      the maximum number of unique sequences (operational taxonomic units roughly
      corresponding to the species level) never exceeded 52,000 in these soils at the
      lowest level of dissimilarity. Furthermore, the bacterial diversity of the forest
      soil was phylum rich compared to the agricultural soils, which are species rich
      but phylum poor. The forest site also showed far less diversity of the Archaea
      with only 0.009% of all sequences from that site being from this group as opposed
      to 4%-12% of the sequences from the three agricultural sites. This work is the
      most comprehensive examination to date of bacterial diversity in soil and
      suggests that agricultural management of soil may significantly influence the
      diversity of bacteria and archaea.

PMID- 18043640
TI  - Contrasting patterns of seed and root colonization by bacteria from the genus
      Chryseobacterium and from the family Oxalobacteraceae.
AB  - Microbial colonization of plant seeds and roots is a highly complex process in
      which soil and plant type can influence the composition of the root-associated
      and rhizosphere microbial communities. Amendment of compost, a common
      agricultural technique, introduces exogenous nutrients and microorganisms to the
      soil-plant environment, and can further influence microbial community composition
      in the plant environment. Although compost amendments can strongly influence soil
      and rhizosphere microbial communities, there is evidence that with increasing
      proximity to the root, plant influences predominate over soil effects. We
      hypothesized that the 'rhizosphere effect' observed with proximity to plant
      surfaces does not act equally on all microorganisms. To explore this issue, we
      examined two bacterial taxa that reproducibly colonized seed and root surfaces in
      an experiment examining the influence of compost amendment on plant-associated
      bacterial communities. Population-specific analyses revealed striking differences
      in the ecology of bacteria from the genus Chryseobacterium and the family
      Oxalobacteraceae in potting mix and plant-associated environments. Seed- and root
      colonizing Oxalobacteraceae populations were highly sensitive to plant effects,
      and phylogenetic analyses of root-colonizing Oxalobacteraceae revealed the
      presence of root-associated populations that were highly similar, regardless of
      treatment, and differed from the potting mix populations detected at the same
      sampling points. Conversely, Chryseobacterium community composition was found to
      be essentially invariant within treatments, but was strongly influenced by
      compost amendment. This persistence and stable nature of the Chryseobacterium
      community composition demonstrates that rhizosphere selection is not the
      exclusive factor involved in determining the composition of the cucumber
      spermosphere and rhizosphere communities.

PMID- 18043641
TI  - Is there a cost of virus resistance in marine cyanobacteria?
AB  - Owing to their abundance and diversity, it is generally perceived that viruses
      are important for structuring microbial communities and regulating biogeochemical
      cycles. The ecological impact of viruses on microbial food webs, however, may be
      influenced by evolutionary processes, including the ability of bacteria to evolve
      resistance to viruses and the theoretical prediction that this resistance should
      be accompanied by a fitness cost. We conducted experiments using phylogenetically
      distinct strains of marine Synechococcus (Cyanobacteria) to test for a cost of
      resistance (COR) to viral isolates collected from Mount Hope Bay, Rhode Island.
      In addition, we examined whether fitness costs (1) increased proportionally with
      'total resistance', the number of viruses for which a strain had evolved
      resistance, or (2) were determined more by 'compositional resistance', the
      identity of the viruses to which it evolved resistance. A COR was only found in
      half of our experiments, which may be attributed to compensatory mutations or the
      inability to detect a small COR. When detected, the COR resulted in a
      approximately 20% reduction in relative fitness compared to ancestral strains.
      The COR was unaffected by total resistance, suggesting a pleiotropic fitness
      response. Under competitive conditions, however, the COR was dependent on
      compositional resistance, suggesting that fitness costs were associated with the
      identity of a few particular viruses. Our study provides the first evidence for a
      COR in marine bacteria, and suggests that Synechococcus production may be
      influenced by the composition of co-occurring viruses.

PMID- 18043642
TI  - Symbiont recognition of mutualistic bacteria by Acromyrmex leaf-cutting ants.
AB  - Symbiont choice has been proposed to play an important role in shaping many
      symbiotic relationships, including the fungus-growing ant-microbe mutualism. Over
      millions of years, fungus-growing ants have defended their fungus gardens from
      specialized parasites with antibiotics produced by an actinomycete bacterial
      mutualist (genus Pseudonocardia). Despite the potential of being infected by
      phylogenetically diverse strains of parasites, each ant colony maintains only a
      single Pseudonocardia symbiont strain, which is primarily vertically transmitted
      between colonies by the founding queens. In this study, we show that Acromyrmex
      leaf-cutter ants are able to differentiate between their native actinomycete
      strain and a variety of foreign strains isolated from sympatric and allopatric
      Acromyrmex species, in addition to strains originating from other fungus-growing
      ant genera. The recognition mechanism is sufficiently sensitive for the ants to
      discriminate between closely related symbiont strains. Our findings suggest that
      symbiont recognition may play a crucial role in the fungus-growing ant-bacterium
      mutualism, likely allowing the ants to retain ecological flexibility necessary
      for defending their garden from diverse parasites and, at the same time, resolve
      potential conflict that can arise from rearing competing symbiont strains.

PMID- 18043643
TI  - Distribution and diversity of phytate-mineralizing bacteria.
AB  - Phytate, the most abundant organic phosphorus compound in soil, dominates the
      biotic phosphorus input from terrestrial runoffs into aquatic systems. Microbial
      mineralization of phytate by phytases is a key process for recycling phosphorus
      in the biosphere. Bioinformatic studies were carried out on microbial genomes and
      environmental metagenomes in the NCBI and the CAMERA databases to determine the
      distribution of the four known classes of phytase in the microbial world. The
      beta-propeller phytase is the only phytase family that can be found in aquatic
      environments and it is also distributed in soil and plant bacteria. The beta
      propeller phytase-like genes can be classified into several subgroups based on
      their domain structure and the positions of their conserved cysteine residues.
      Analysis of the genetic contexts of these subgroups showed that beta-propeller
      phytase genes exist either as an independent gene or are closely associated with
      a TonB-dependent receptor-like gene in operons, suggesting that these two genes
      are functionally linked and thus may play an important role in the cycles of
      phosphorus and iron. Our work suggests that beta-propeller phytases play a major
      role in phytate-phosphorus cycling in both soil and aquatic microbial
      communities.

PMID- 18043644
TI  - Sequence-based analysis of pQBR103; a representative of a unique, transfer
      proficient mega plasmid resident in the microbial community of sugar beet.
AB  - The plasmid pQBR103 was found within Pseudomonas populations colonizing the leaf
      and root surfaces of sugar beet plants growing at Wytham, Oxfordshire, UK. At 425
      kb it is the largest self-transmissible plasmid yet sequenced from the
      phytosphere. It is known to enhance the competitive fitness of its host, and
      parts of the plasmid are known to be actively transcribed in the plant
      environment. Analysis of the complete sequence of this plasmid predicts a coding
      sequence (CDS)-rich genome containing 478 CDSs and an exceptional degree of
      genetic novelty; 80% of predicted coding sequences cannot be ascribed a function
      and 60% are orphans. Of those to which function could be assigned, 40% bore
      greatest similarity to sequences from Pseudomonas spp, and the majority of the
      remainder showed similarity to other gamma-proteobacterial genera and plasmids.
      pQBR103 has identifiable regions presumed responsible for replication and
      partitioning, but despite being tra+ lacks the full complement of any previously
      described conjugal transfer functions. The DNA sequence provided few insights
      into the functional significance of plant-induced transcriptional regions, but
      suggests that 14% of CDSs may be expressed (11 CDSs with functional annotation
      and 54 without), further highlighting the ecological importance of these novel
      CDSs. Comparative analysis indicates that pQBR103 shares significant regions of
      sequence with other plasmids isolated from sugar beet plants grown at the same
      geographic location. These plasmid sequences indicate there is more novelty in
      the mobile DNA pool accessible to phytosphere pseudomonas than is currently
      appreciated or understood.

PMID- 18043645
TI  - Biological and chemical sulfide oxidation in a Beggiatoa inhabited marine
      sediment.
AB  - The ecological niche of nitrate-storing Beggiatoa, and their contribution to the
      removal of sulfide were investigated in coastal sediment. With microsensors a
      clear suboxic zone of 2-10 cm thick was identified, where neither oxygen nor free
      sulfide was detectable. In this zone most of the Beggiatoa were found, where they
      oxidize sulfide with internally stored nitrate. The sulfide input into the
      suboxic zone was dominated by an upward sulfide flux from deeper sediment,
      whereas the local production in the suboxic zone was much smaller. Despite their
      abundance, the calculated sulfide-oxidizing capacity of the Beggiatoa could
      account for only a small fraction of the total sulfide removal in the sediment.
      Consequently, most of the sulfide flux into the suboxic layer must have been
      removed by chemical processes, mainly by precipitation with Fe2+ and oxidation by
      Fe(III), which was coupled with a pH increase. The free Fe2+ diffusing upwards
      was oxidized by Mn(IV), resulting in a strong pH decrease. The nitrate storage
      capacity allows Beggiatoa to migrate randomly up and down in anoxic sediments
      with an accumulated gliding distance of 4 m before running out of nitrate. We
      propose that the steep sulfide gradient and corresponding high sulfide flux, a
      typical characteristic of Beggiatoa habitats, is not needed for their metabolic
      performance, but rather used as a chemotactic cue by the highly motile filaments
      to avoid getting lost at depth in the sediment. Indeed sulfide is a repellent for
      Beggiatoa.

PMID- 18043646
TI  - Carbon and nitrogen fixation and metabolite exchange in and between individual
      cells of Anabaena oscillarioides.
AB  - Filamentous nitrogen fixing cyanobacteria are key players in global nutrient
      cycling, but the relationship between CO2- and N2-fixation and intercellular
      exchange of these elements remains poorly understood in many genera. Using high
      resolution nanometer-scale secondary ion mass spectrometry (NanoSIMS) in
      conjunction with enriched H13CO3- and 15N2 incubations of Anabaena
      oscillarioides, we imaged the cellular distributions of C, N and P and 13C and
      15N enrichments at multiple time points during a diurnal cycle as proxies for C
      and N assimilation. The temporal and spatial distributions of the newly fixed C
      and N were highly heterogeneous at both the intra- and inter-cellular scale, and
      indicative of regions performing active assimilation and biosynthesis.
      Subcellular components such as the neck region of heterocycts, cell division
      septae and putative cyanophycin granules were clearly identifiable by their
      elemental composition. Newly fixed nitrogen was rapidly exported from heterocysts
      and was evenly allocated among vegetative cells, with the exception of the most
      remote vegetative cells between heterocysts, which were N limited based on lower
      15N enrichment. Preexisting functional heterocysts had the lowest levels of 13C
      and 15N enrichment, while heterocysts that were inferred to have differentiated
      during the experiment had higher levels of enrichment. This innovative approach,
      combining stable isotope labeling and NanoSIMS elemental and isotopic imaging,
      allows characterization of cellular development (division, heterocyst
      differentiation), changes in individual cell composition and cellular roles in
      metabolite exchange.

PMID- 18043648
TI  - The marine microbial world: a voyage of discovery.

PMID- 18043647
TI  - Improvements of high-throughput culturing yielded novel SAR11 strains and other
      abundant marine bacteria from the Oregon coast and the Bermuda Atlantic Time
      Series study site.
AB  - The introduction of high-throughput dilution-to-extinction culturing (HTC) of
      marine bacterioplankton using sterilized natural sea water as media yielded
      isolates of many abundant but previously uncultured marine bacterial clades. In
      early experiments, bacteria from the SAR11 cluster (class Alphaproteobacteria),
      which are presumed to be the most abundant prokaryotes on earth, were cultured.
      Although many additional attempts were made, no further strains of the SAR11
      clade were obtained. Here, we describe improvements to the HTC technique, which
      led to the isolation of 17 new SAR11 strains from the Oregon coast and the
      Sargasso Sea, accounting for 28% and 31% of all isolates in these experiments.
      Phylogenetic analysis of the internal transcribed spacer (ITS) region showed that
      the isolates from the Oregon coast represent three different subclusters of
      SAR11, while isolates from the Sargasso Sea were more uniform and represented a
      single ITS cluster. A PCR assay proved the presence of proteorhodopsin (PR) in
      nearly all SAR11 isolates. Analysis of PR amino-acid sequences indicated that
      isolates from the Oregon coast were tuned to either green or blue light, while
      PRs from strains obtained from the Sargasso Sea were exclusively tuned to maximum
      absorbance in the blue. Interestingly, phylogenies based on PR and ITS did not
      correlate, suggesting lateral gene transfer. In addition to the new SAR11
      strains, many novel strains belonging to clusters of previously uncultured or
      undescribed species of different bacterial phyla, including the first strain of
      the highly abundant alphaproteobacterial SAR116 clade, were isolated using the
      modified methods.

PMID- 18043649
TI  - Reductive dechlorination of chloroethenes by Dehalococcoides-containing cultures
      enriched from a polychlorinated-dioxin-contaminated microcosm.
AB  - The reductive dechlorinating abilities for chloroethenes of seven enrichment
      cultures from polychlorinated-dioxin-dechlorinating microcosm were investigated
      using culture-independent and -dependent methods. These cultures were constructed
      and maintained with 1,2,3-trichlorobenzene (1,2,3-TCB) or fthalide as an electron
      acceptor and hydrogen as an electron donor. Denaturing gradient gel
      electrophoresis (DGGE) analysis of the amplified fragments targeting the 16S rRNA
      gene showed one or two major bands, whose nucleotide sequences were then analyzed
      and were found to suggest that Dehalococcoides was one of the dominant bacteria
      in all enrichment cultures. The nucleotide sequence data revealed that the
      identity of the major band was 100% identical to the 16S rRNA gene sequence of
      the Pinellas subgroup of the Dehalococcoides clusters, that is, strains CBDB1 and
      FL2. Genetic diagnosis targeting the pceA, tceA, bvcA, vcrA and reductive
      dehalogenase homologous (rdh) gene was performed to investigate the potential for
      reductive chloroethene dechlorination of cultures. The required length of PCR
      amplified fragments was not observed, suggesting that these cultures are not
      capable of reductively dechlorinating chloroethenes. However, a culture-dependent
      test indicated that two cultures, TUT1903 and TUT1952, reductively dechlorinated
      tetrachloroethene (PCE) to trichloroethene (TCE), although not completely. While,
      TUT2260 and TUT2264 completely converted PCE to TCE and dichloroethenes, but not
      further. These results suggest that these TUT cultures might include a novel type
      of bacteria belonging to the Dehalococcoides group and that currently available
      information on both the 16S rRNA gene and rdh gene sequences is insufficient to
      definitively evaluate the potential abilities for reductive dechlorination.

PMID- 18043650
TI  - Stable-isotope probing implicates Methylophaga spp and novel Gammaproteobacteria
      in marine methanol and methylamine metabolism.
AB  - The metabolism of one-carbon (C(1)) compounds in the marine environment affects
      global warming, seawater ecology and atmospheric chemistry. Despite their global
      significance, marine microorganisms that consume C(1) compounds in situ remain
      poorly characterized. Stable-isotope probing (SIP) is an ideal tool for linking
      the function and phylogeny of methylotrophic organisms by the metabolism and
      incorporation of stable-isotope-labelled substrates into nucleic acids. By
      combining DNA-SIP and time-series sampling, we characterized the organisms
      involved in the assimilation of methanol and methylamine in coastal sea water
      (Plymouth, UK). Labelled nucleic acids were analysed by denaturing gradient gel
      electrophoresis (DGGE) and clone libraries of 16S rRNA genes. In addition, we
      characterized the functional gene complement of labelled nucleic acids with an
      improved primer set targeting methanol dehydrogenase (mxaF) and newly designed
      primers for methylamine dehydrogenase (mauA). Predominant DGGE phylotypes, 16S
      rRNA, methanol and methylamine dehydrogenase gene sequences, and cultured
      isolates all implicated Methylophaga spp, moderately halophilic marine
      methylotrophs, in the consumption of both methanol and methylamine. Additionally,
      an mxaF sequence obtained from DNA extracted from sea water clustered with those
      detected in (13)C-DNA, suggesting a predominance of Methylophaga spp among marine
      methylotrophs. Unexpectedly, most predominant 16S rRNA and functional gene
      sequences from (13)C-DNA were clustered in distinct substrate-specific clades,
      with 16S rRNA genes clustering with sequences from the Gammaproteobacteria. These
      clades have no cultured representatives and reveal an ecological adaptation of
      particular uncultured methylotrophs to specific C(1) compounds in the coastal
      marine environment.

PMID- 18043651
TI  - Viral photosynthetic reaction center genes and transcripts in the marine
      environment.
AB  - Cyanobacteria of the genera Synechococcus and Prochlorococcus are important
      contributors to photosynthetic productivity in the open ocean. The discovery of
      genes (psbA, psbD) that encode key photosystem II proteins (D1, D2) in the
      genomes of phages that infect these cyanobacteria suggests new paradigms for the
      regulation, function and evolution of photosynthesis in the vast pelagic
      ecosystem. Reports on the prevalence and expression of phage photosynthesis
      genes, and evolutionary data showing a potential recombination of phage and host
      genes, suggest a model in which phage photosynthesis genes help support
      photosynthetic activity in their hosts during the infection process. Here, using
      metagenomic data in natural ocean samples, we show that about 60% of the psbA
      genes in surface water along the global ocean sampling transect are of phage
      origin, and that the phage genes are undergoing an independent selection for
      distinct D1 proteins. Furthermore, we show that different viral psbA genes are
      expressed in the environment.

PMID- 18043652
TI  - High specificity but contrasting biodiversity of Sphagnum-associated bacterial
      and plant communities in bog ecosystems independent of the geographical region.
AB  - Mosses represent ecological niches that harbor a hitherto largely uncharacterized
      microbial diversity. To investigate which factors affect the biodiversity of
      bryophyte-associated bacteria, we analyzed the bacterial communities associated
      with two moss species, which exhibit different ecological behaviors and
      importance in bog ecosystems, Sphagnum magellanicum and Sphagnum fallax, from six
      temperate and boreal bogs in Germany and Norway. Furthermore, their surrounding
      plant communities were studied. Molecular analysis of bacterial communities was
      determined by single-strand conformation polymorphism (SSCP) analysis using
      eubacterial and genus-specific primers for the dominant genera Burkholderia and
      Serratia as well as by sequence analysis of a Burkholderia 16S rRNA gene clone
      library. Plant communities were analyzed by monitoring the abundance and
      composition of bryophyte and vascular plant species, and by determining
      ecological indicator values. Interestingly, we found a high degree of host
      specificity for associated bacterial and plant communities of both Sphagnum
      species independent of the geographical region. Calculation of diversity indices
      on the basis of SSCP gels showed that the S. fallax-associated communities
      displayed a statistically significant higher degree of diversity than those
      associated with S. magellanicum. In contrast, analyses of plant communities of
      Sphagnum-specific habitats resulted in a higher diversity of S. magellanicum
      specific habitats for all six sites. The higher content of nutrients in the S.
      fallax-associated ecosystems can explain higher diversity of microorganisms.

PMID- 18043653
TI  - Phytoplankton carbon fixation gene (RuBisCO) transcripts and air-sea CO(2) flux
      in the Mississippi River plume.
AB  - River plumes deliver large quantities of nutrients to oligotrophic oceans, often
      resulting in significant CO(2) drawdown. To determine the relationship between
      expression of the major gene in carbon fixation (large subunit of ribulose-1,5
      bisphosphate carboxylase/oxygenase, RuBisCO) and CO(2) dynamics, we evaluated
      rbcL mRNA abundance using novel quantitative PCR assays, phytoplankton cell
      analyses, photophysiological parameters, and pCO(2) in and around the Mississippi
      River plume (MRP) in the Gulf of Mexico. Lower salinity (30-32) stations were
      dominated by rbcL mRNA concentrations from heterokonts, such as diatoms and
      pelagophytes, which were at least an order of magnitude greater than haptophytes,
      alpha-Synechococcus or high-light Prochlorococcus. However, rbcL transcript
      abundances were similar among these groups at oligotrophic stations (salinity 34
      36). Diatom cell counts and heterokont rbcL RNA showed a strong negative
      correlation to seawater pCO(2). While Prochlorococcus cells did not exhibit a
      large difference between low and high pCO(2) water, Prochlorococcus rbcL RNA
      concentrations had a strong positive correlation to pCO(2), suggesting a very low
      level of RuBisCO RNA transcription among Prochlorococcus in the plume waters,
      possibly due to their relatively poor carbon concentrating mechanisms (CCMs).
      These results provide molecular evidence that diatom/pelagophyte productivity is
      largely responsible for the large CO(2) drawdown occurring in the MRP, based on
      the co-occurrence of elevated RuBisCO gene transcript concentrations from this
      group and reduced seawater pCO(2) levels. This may partly be due to efficient
      CCMs that enable heterokont eukaryotes such as diatoms to continue fixing CO(2)
      in the face of strong CO(2) drawdown. Our work represents the first attempt to
      relate in situ microbial gene expression to contemporaneous CO(2) flux
      measurements in the ocean.

PMID- 18043654
TI  - Links between bacterial production, amino-acid utilization and community
      composition in productive lakes.
AB  - Influence of distribution and abundance of bacterial taxa on ecosystem function
      are poorly understood for natural microbial communities. We related 16S rRNA
      based terminal restriction fragment length polymorphism to bacterial production
      and arginine uptake kinetics to test if functional features of bacterioplankton
      in four lakes could be predicted from community composition. Maximum arginine
      uptake rate (arginine V(max)) ranged from 10% to 100% of bacterial production.
      Owing to high growth efficiencies on arginine (63-77%), the bacterial community
      could potentially saturate its carbon demand using this single organic substrate,
      for example, during sudden surges of free amino acids. However, due to low in
      situ concentrations of arginine in these lakes (<0.9 microg l(-1)), actual uptake
      rates at ambient concentrations rarely exceeded 10% of V(max). Bacterial
      production and arginine V(max) could be predicted from a subset of bacterial
      ribotypes, tentatively affiliated with several bacterial divisions
      (Cyanobacteria, Actinobacteria, Bacteroidetes and Proteobacteria). Multivariate
      statistical analysis indicates that there were both highly important and less
      important ribotypes for the prediction of bacterial production and arginine
      V(max). These populations were either negatively or positively related to the
      respective functional feature, indicating contrasting ecological roles. Our study
      provides a statistically robust demonstration that, apart from environmental
      conditions, patterns in bacterial community composition can also be used to
      predict lake ecosystem function.

PMID- 18043655
TI  - Effect of organic forms of phosphorus and variable concentrations of sulfide on
      the metabolic generation of soluble-reactive phosphate by sulfur
      chemolithoautotrophs: a laboratory study.
AB  - In aquatic systems, recycling of phosphorus (P) is strongly influenced by
      microbial metabolic responses. This study was designed to look at the generation
      of P (as soluble-reactive phosphate (SRP)) from organic P-enriched sediments by
      benthic sulfur chemolithoautotrophs. The study revealed that microbial density
      was greater in organic P-enriched sediments when compared to sediments without
      added organic P and the presence of organic P significantly influenced
      mobilization of SRP from sediment. Generation of SRP by sediment microbes was
      cumulative, dependent on time. The results indicated dissolved sulfide (S(2-)) to
      be necessary for initiation of the metabolism-related mobilization of P: there
      was no statistically significant effect of variations in ambient concentrations
      of sulfide (S(2-)). The results elucidate possible outcomes of addition of
      organic P in aquatic ecosystems.

PMID- 18043656
TI  - Hydrogen is the central free intermediate during lignocellulose degradation by
      termite gut symbionts.
AB  - The key role of free hydrogen in the digestion of lignocellulose by wood-feeding
      lower termites and their symbiotic gut microbiota has been conceptually outlined
      in the past decades but remains to be quantitatively analyzed in situ. Using
      Reticulitermes santonensis, Zootermopsis nevadensis and Cryptotermes secundus, we
      determined metabolite fluxes involved in hydrogen turnover and the resulting
      distribution of H(2) in the microliter-sized gut. High-resolution hydrogen
      microsensor profiles revealed pronounced differences in hydrogen accumulation
      among the species (from <1 kPa to the saturation level). However, flux
      measurements indicated that the hydrogen pool was rapidly turned over in all
      termites, irrespective of the degree of accumulation. Microinjection of
      radiotracers into intact guts confirmed that reductive acetogenesis from CO(2)
      dominated hydrogen consumption, whereas methanogenesis played only a minor role.
      Only negligible amounts of H(2) were lost by emission, documenting an overall
      equilibrium between hydrogen production and consumption within the gut.
      Mathematical modeling revealed that production dominates in the gut lumen and
      consumption in the gut periphery for R. santonensis and Z. nevadensis, explaining
      the large accumulation of H(2) in these termites, whereas the moderate hydrogen
      accumulation in C. secundus indicated a more balanced radial distribution of the
      two processes. Daily hydrogen turnover rates were 9-33 m(3) H(2) per m(3) hindgut
      volume, corresponding to 22-26% of the respiratory activity of the termites. This
      makes H(2) the central free intermediate during lignocellulose degradation and
      the termite gut-with its high rates of reductive acetogenesis-the smallest and
      most efficient natural bioreactor currently known.

PMID- 18043657
TI  - Labile associations between fungus-growing ant cultivars and their garden
      pathogens.
AB  - The distribution of genetic and phenotypic variation in both hosts and parasites
      over their geographic ranges shapes coevolutionary dynamics. Specifically,
      concordant host and parasite distributions facilitate localized adaptation and
      further specialization of parasite genotypes on particular host genotypes. We
      here compare genetic population structure of the cultivated fungi of the fungus
      growing ant Apterostigma dentigerum and of the cultivar-attacking fungus,
      Escovopsis, to determine whether these microbial associations have evolved or are
      likely to evolve genotype-genotype specialization. Analyses based on amplified
      fragment length polymorphism (AFLP) genotyping of host cultivars and pathogenic
      Escovopsis from 77 A. dentigerum colonies reveal that populations of hosts and
      pathogens are not similarly diverged and that host and pathogen genetic distances
      are uncorrelated, indicating that genetically similar parasites are not infecting
      genetically similar hosts. Microbial bioassays between pathogens and cultivars of
      different genotypes and from different populations show little pairwise
      specificity; most Escovopsis strains tested can successfully infect all cultivar
      strains with which they are paired. These molecular and experimental data suggest
      that Escovopsis genotypes are not tightly tracking cultivar genotypes within the
      A. dentigerum system. The diffuse nature of this host-pathogen association, in
      which pathogen genotypes are not interacting with a single host genotype but
      instead with many different hosts, will influence evolutionary and ecological
      disease dynamics of the fungus-growing ant-microbe symbiosis.

PMID- 18043658
TI  - Experimental demonstration of chaotic instability in biological nitrification.
AB  - Biological nitrification (that is, NH(3) --> NO(2)(-) --> NO(3)(-)) is a key
      reaction in the global nitrogen cycle (N-cycle); however, it is also known
      anecdotally to be unpredictable and sometimes fails inexplicably. Understanding
      the basis of unpredictability in nitrification is critical because the loss or
      impairment of this function might influence the balance of nitrogen in the
      environment and also has biotechnological implications. One explanation for
      unpredictability is the presence of chaotic behavior; however, proving such
      behavior from experimental data is not trivial, especially in a complex microbial
      community. Here, we show that chaotic behavior is central to stability in
      nitrification because of a fragile mutualistic relationship between ammonia
      oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB), the two major
      guilds in nitrification. Three parallel chemostats containing mixed microbial
      communities were fed complex media for 207 days, and nitrification performance,
      and abundances of AOB, NOB, total bacteria and protozoa were quantified over
      time. Lyapunov exponent calculations, supported by surrogate data and other
      tests, showed that all guilds were sensitive to initial conditions, suggesting
      broad chaotic behavior. However, NOB were most unstable among guilds and
      displayed a different general pattern of instability. Further, NOB variability
      was maximized when AOB were most unstable, which resulted in erratic
      nitrification including significant NO(2)(-) accumulation. We conclude that
      nitrification is prone to chaotic behavior because of a fragile AOB-NOB
      mutualism, which must be considered in all systems that depend on this critical
      reaction.

PMID- 18043659
TI  - Comparative microbiota of Rickettsia felis-uninfected and -infected colonized cat
      fleas, Ctenocephalides felis.
AB  - Fleas serve as arthropod vectors for several emerging and re-emerging infectious
      disease causing agents including, Rickettsia felis. Although the prevalence of R.
      felis infection in colonies of fleas has been examined, the influence of the R.
      felis infection on flea microbiota has not been investigated. We identified three
      colonies of cat fleas, Ctenocephalides felis, with varying prevalence of R. felis
      infection (Louisiana State University (LSU), 93.8%; Professional Laboratory and
      Research Services Inc. (PLRS), 16.4%; Elward II (EL), 0%) and subsequently
      utilized polymerase chain reaction amplification, restriction fragment length
      polymorphism analysis and sequencing of the 1.4-kb portions of 16S rRNA genes to
      examine the diversity of bacteria in the flea populations. A total of 17
      different bacterial 16S rRNA gene sequences were identified among the C. felis
      colonies. The prevalence of two Wolbachia species that were identified in each
      flea colony differed between colonies and R. felis-uninfected and -infected
      fleas. Species richness was unchanged among the R. felis-uninfected (LSU, PLRS
      and EL colonies) and -infected (LSU and PLRS colonies) fleas; however, between R.
      felis-uninfected and -infected fleas within both the LSU and PLRS colonies, R.
      felis-uninfected fleas have greater species richness. Diversity indices did not
      identify a difference in diversity between any of the flea samples. The
      interaction of endosymbionts within arthropods can widely impact the
      dissemination of vertically transmitted pathogenic bacteria; and the reciprocal
      may be true. These results suggest that carriage of R. felis has an impact on the
      richness of flea microbiota.

PMID- 18043661
TI  - Fosmids of novel marine Planctomycetes from the Namibian and Oregon coast
      upwelling systems and their cross-comparison with planctomycete genomes.
AB  - Planctomycetes are widely distributed in marine environments, where they
      supposedly play a role in carbon recycling. To deepen our understanding about the
      ecology of this sparsely studied phylum six planctomycete fosmids from two marine
      upwelling systems were investigated and compared with all available planctomycete
      genomic sequences including the as yet unpublished near-complete genomes of
      Blastopirellula marina DSM 3645(T) and Planctomyces maris DSM 8797(T). High
      numbers of sulfatase genes (41-109) were found on all marine planctomycete
      genomes and on two fosmids (2). Furthermore, C1 metabolism genes otherwise only
      known from methanogenic Archaea and methylotrophic Proteobacteria were found on
      two fosmids and all planctomycete genomes, except for 'Candidatus Kuenenia
      stuttgartiensis'. Codon usage analysis indicated high expression levels for some
      of these genes. In addition, novel large families of planctomycete-specific
      paralogs with as yet unknown functions were identified, which are notably absent
      from the genome of 'Candidatus Kuenenia stuttgartiensis'. The high numbers of
      sulfatases in marine planctomycetes characterizes them as specialists for the
      initial breakdown of sulfatated heteropolysaccharides and indicate their
      importance for recycling carbon from these compounds. The almost ubiquitous
      presence of C1 metabolism genes among Planctomycetes together with codon usage
      analysis and information from the genomes suggest a general importance of these
      genes for Planctomycetes other than formaldehyde detoxification. The notable
      absence of these genes in Candidatus K. stuttgartiensis plus the surprising lack
      of almost any planctomycete-specific gene within this organism reveals an
      unexpected distinctiveness of anammox bacteria from all other Planctomycetes.

PMID- 18043662
TI  - Anaerobic phenanthrene mineralization by a carboxylating sulfate-reducing
      bacterial enrichment.
AB  - Information on the susceptibility of higher molecular weight polynuclear aromatic
      hydrocarbons to anaerobic biodegradation is relatively rare. We obtained a
      sulfate-reducing bacterial enrichment capable of phenanthrene metabolism from a
      hydrocarbon-contaminated marine sediment. Phenanthrene degradation was in
      stoichiometric agreement with the theoretically expected amount of sulfate
      reduction and inhibited by molybdate. Mineralization of (14)C-phenanthrene by the
      enrichment was confirmed by the recovery of the expected amount of (14)CO(2).
      Stable isotope studies with protonated or deuterated phenanthrene resulted in the
      detection of the correspondingly labeled phenanthrene carboxylic acid by gas
      chromatography-mass spectrometry. Comparison of the metabolite profile with a
      synthesized standard confirmed that the parent molecule was carboxylated at the C
      2 position. Incorporation of (13)C-bicarbonate into the carboxyl group implicated
      a direct carboxylation of phenanthrene as a likely key initial reaction.
      Denaturing gradient gel electrophoresis analysis of the enrichment showed only
      two major bands and 16S rRNA sequences obtained by cloning clustered with known
      hydrocarbon-degrading sulfate-reducing delta-proteobacteria, indicating their
      possible involvement in the anaerobic oxidation of phenanthrene via carboxylation
      as the initial activation reaction.

PMID- 18043663
TI  - Effects of cattle husbandry on abundance and activity of methanogenic archaea in
      upland soils.
AB  - In the present study, we tested the hypothesis that animal treading associated
      with a high input of organic matter would favour methanogenesis in soils used as
      overwintering pasture. Hence, methane emissions and methanogen populations were
      examined at sections with different degree of cattle impact in a Farm in South
      Bohemia, Czech Republic. In spring, methane emission positively corresponded to
      the gradient of animal impact. Applying phospholipid etherlipid analysis, the
      highest archaeal biomass was found in section severe impact (SI), followed by
      moderate impact (MI) and no impact. The same trend was observed for the
      methanogens as showed by real-time quantitative PCR analyses of methyl coenzyme M
      reductase (mcrA) genes. The detection of monounsaturated isoprenoid side chain
      hydrocarbons (i20:1) indicated the presence of acetoclastic methanogens in the
      cattle-impacted sites. This result was corroborated by the phylogenetic analysis
      of mcrA gene sequences obtained from section SI, which showed that 33% of the
      analysed clones belonged to the genus Methanosarcina. The majority of the
      sequenced clones (41%) showed close affiliations with uncultured rumen archaeons.
      This leads to the assumption that a substantial part of the methanogenic
      community in plot SI derived from the grazing cattle itself. Compared to the
      spring sampling, in autumn, a significant reduction in archaeal biomass and
      number of copies of mcrA genes was observed mainly for section MI. It can be
      concluded that after 5 months without cattle impact, the severely impact section
      maintained its methane production potential, whereas the methane production
      potential under moderate impact returned to background values.

PMID- 18043660
TI  - Culture independent analysis of ileal mucosa reveals a selective increase in
      invasive Escherichia coli of novel phylogeny relative to depletion of
      Clostridiales in Crohn's disease involving the ileum.
AB  - Intestinal bacteria are implicated increasingly as a pivotal factor in the
      development of Crohn's disease, but the specific components of the complex
      polymicrobial enteric environment driving the inflammatory response are
      unresolved. This study addresses the role of the ileal mucosa-associated
      microflora in Crohn's disease. A combination of culture-independent analysis of
      bacterial diversity (16S rDNA library analysis, quantitative PCR and fluorescence
      in situ hybridization) and molecular characterization of cultured bacteria was
      used to examine the ileal mucosa-associated flora of patients with Crohn's
      disease involving the ileum (13), Crohn's disease restricted to the colon (CCD)
      (8) and healthy individuals (7). Analysis of 16S rDNA libraries constructed from
      ileal mucosa yielded nine clades that segregated according to their origin
      (P<0.0001). 16S rDNA libraries of ileitis mucosa were enriched in sequences for
      Escherichia coli (P<0.001), but relatively depleted in a subset of Clostridiales
      (P<0.05). PCR of mucosal DNA was negative for Mycobacterium avium subspecies
      paratuberculosis, Shigella and Listeria. The number of E. coli in situ correlated
      with the severity of ileal disease (rho 0.621, P<0.001) and invasive E. coli was
      restricted to inflamed mucosa. E. coli strains isolated from the ileum were
      predominantly novel in phylogeny, displayed pathogen-like behavior in vitro and
      harbored chromosomal and episomal elements similar to those described in
      extraintestinal pathogenic E. coli and pathogenic Enterobacteriaceae. These data
      establish that dysbiosis of the ileal mucosa-associated flora correlates with an
      ileal Crohn's disease (ICD) phenotype, and raise the possibility that a selective
      increase in a novel group of invasive E. coli is involved in the etiopathogenesis
      to Crohn's disease involving the ileum.

PMID- 18043664
TI  - High diversity of bacterial mercuric reductase genes from surface and sub-surface
      floodplain soil (Oak Ridge, USA).
AB  - DNA was extracted from different depth soils (0-5, 45-55 and 90-100 cm below
      surface) sampled at Lower East Fork Poplar Creek floodplain (LEFPCF), Oak Ridge
      (TN, USA). The presence of merA genes, encoding the mercuric reductase, the key
      enzyme in detoxification of mercury in bacteria, was examined by PCR targeting
      Actinobacteria, Firmicutes or beta/gamma-Proteobacteria. beta/gamma
      Proteobacteria merA genes were successfully amplified from all soils, whereas
      Actinobacteria were amplified only from surface soil. merA clone libraries were
      constructed and sequenced. beta/gamma-Proteobacteria sequences revealed high
      diversity in all soils, but limited vertical similarity. Less than 20% of the
      operational taxonomic units (OTU) (DNA sequences > or = 95% identical) were
      shared between the different soils. Only one of the 62 OTU was > or = 95%
      identical to a GenBank sequence, highlighting that cultivated bacteria are not
      representative of what is found in nature. Fewer merA sequences were obtained
      from the Actinobacteria, but these were also diverse, and all were different from
      GenBank sequences. A single clone was most closely related to merA of alpha
      Proteobacteria. An alignment of putative merA genes of genome sequenced mainly
      marine alpha-Proteobacteria was used for design of merA primers. PCR
      amplification of soil alpha-Proteobacteria isolates and sequencing revealed that
      they were very different from the genome-sequenced bacteria (only 62%-66%
      identical at the amino-acid level), although internally similar. In light of the
      high functional diversity of mercury resistance genes and the limited vertical
      distribution of shared OTU, we discuss the role of horizontal gene transfer as a
      mechanism of bacterial adaptation to mercury.

PMID- 18043665
TI  - The geomicrobiology of gold.
AB  - Microorganisms capable of actively solubilizing and precipitating gold appear to
      play a larger role in the biogeochemical cycling of gold than previously
      believed. Recent research suggests that bacteria and archaea are involved in
      every step of the biogeochemical cycle of gold, from the formation of primary
      mineralization in hydrothermal and deep subsurface systems to its solubilization,
      dispersion and re-concentration as secondary gold under surface conditions.
      Enzymatically catalysed precipitation of gold has been observed in thermophilic
      and hyperthermophilic bacteria and archaea (for example, Thermotoga maritime,
      Pyrobaculum islandicum), and their activity led to the formation of gold- and
      silver-bearing sinters in New Zealand's hot spring systems. Sulphate-reducing
      bacteria (SRB), for example, Desulfovibrio sp., may be involved in the formation
      of gold-bearing sulphide minerals in deep subsurface environments; over
      geological timescales this may contribute to the formation of economic deposits.
      Iron- and sulphur-oxidizing bacteria (for example, Acidothiobacillus
      ferrooxidans, A. thiooxidans) are known to breakdown gold-hosting sulphide
      minerals in zones of primary mineralization, and release associated gold in the
      process. These and other bacteria (for example, actinobacteria) produce
      thiosulphate, which is known to oxidize gold and form stable, transportable
      complexes. Other microbial processes, for example, excretion of amino acids and
      cyanide, may control gold solubilization in auriferous top- and rhizosphere
      soils. A number of bacteria and archaea are capable of actively catalysing the
      precipitation of toxic gold(I/III) complexes. Reductive precipitation of these
      complexes may improve survival rates of bacterial populations that are capable of
      (1) detoxifying the immediate cell environment by detecting, excreting and
      reducing gold complexes, possibly using P-type ATPase efflux pumps as well as
      membrane vesicles (for example, Salmonella enterica, Cupriavidus (Ralstonia)
      metallidurans, Plectonema boryanum); (2) gaining metabolic energy by utilizing
      gold-complexing ligands (for example, thiosulphate by A. ferrooxidans) or (3)
      using gold as metal centre in enzymes (Micrococcus luteus). C. metallidurans
      containing biofilms were detected on gold grains from two Australian sites,
      indicating that gold bioaccumulation may lead to gold biomineralization by
      forming secondary 'bacterioform' gold. Formation of secondary octahedral gold
      crystals from gold(III) chloride solution, was promoted by a cyanobacterium (P.
      boryanum) via an amorphous gold(I) sulphide intermediate. 'Bacterioform' gold and
      secondary gold crystals are common in quartz pebble conglomerates (QPC), where
      they are often associated with bituminous organic matter possibly derived from
      cyanobacteria. This may suggest that cyanobacteria have played a role in the
      formation of the Witwatersrand QPC, the world's largest gold deposit.

PMID- 18043666
TI  - Effects of ciprofloxacin on salt marsh sediment microbial communities.
AB  - Fluoroquinolones, a widely used class of antibiotics, are frequently detected in
      sediments and surface waters. Given their antimicrobial properties, the presence
      of these compounds may alter the composition of microbial communities and promote
      antibiotic resistance in the environment. The purpose of this study was to
      measure sorption, and effects of ciprofloxacin on microbial community
      composition, in sediment samples from three California salt marshes. Sediments
      were exposed to a ciprofloxacin concentration gradient (0-200 microg ml(-1)
      ciprofloxacin) and microbial community composition characterized using
      phospholipid fatty acid (PLFA) analysis. Sorption coefficients, expressed as log
      K(d), were calculated from fits using the Freundlich isotherm model.
      Ciprofloxacin strongly sorbed to all sediments and had log K(d) values, ranging
      from 2.9 to 4.3. Clay content was positively (r(2)=0.98) and pH negatively
      (r(2)=0.99) correlated to K(d) values. Biomass, PLFA richness, sulfate reducer
      and Gram-negative bacteria markers increased with ciprofloxacin concentrations,
      while the 17 cy/precursor and saturated/unsaturated biomarker ratios, indicators
      of starvation stress, decreased. The magnitude of the effect of ciprofloxacin on
      microbial communities was inversely correlated to the degree of sorption to the
      sediments. Despite the fact that ciprofloxacin is a wide-spectrum antibiotic, its
      impact on sediment microbial communities was selective and appeared to favor
      sulfate-reducing bacteria and Gram-negative bacteria.

PMID- 18043667
TI  - The biogeographical distribution of closely related freshwater sediment bacteria
      is determined by environmental selection.
AB  - The role of environmental selection in governing the structure of communities of
      freshwater sulfur bacteria (Achromatium spp) was experimentally tested by mixing
      sediments from two geographically separated lakes (Rydal Water (RY) and Hell
      Kettles (HK)) that harboured Achromatium spp. Community profiles of Achromatium
      spp in sediment microcosms at day 0 and after 60 days were compared to determine
      whether initial Achromatium community composition or subsequent selection by the
      sediment environment had greater influence in dictating the final Achromatium
      community structure. It was found that Achromatium spp from the HK community
      became established in mixed sediments at the expense of members of the RY
      community. This selection for the HK Achromatium community was more pronounced
      when sediment composition was manipulated to resemble HK sediments. Our findings
      definitively demonstrate that environmental selection is the primary determinant
      of Achromatium community structure in these sediments.

PMID- 18043668
TI  - Modeled contributions of three types of diazotrophs to nitrogen fixation at
      Station ALOHA.
AB  - A diagnostic model based on biomass and growth was used to assess the relative
      contributions of filamentous nonheterocystous Trichodesmium and unicellular
      cyanobacteria, termed Groups A and B, to nitrogen fixation at the North Pacific
      Station ALOHA over a 2-year period. Average (and 95% confidence interval, CI)
      annual rates of modeled monthly values for Trichodesmium, Group B and Group A
      were 92 (52), 14 (4) and 12 (8) mmol N per m(2) per year, respectively. The
      fractional contribution to modeled instantaneous nitrogen fixation by each
      diazotroph fluctuated on interannual, seasonal and shorter time scales.
      Trichodesmium fixed substantially more nitrogen in year 1 (162) than year 2 (12).
      Group B fixed almost two times more nitrogen in year 1 (17) than year 2 (9). In
      contrast, Group A fixed two times more nitrogen in year 2 (16) than year 1 (8).
      When including uncertainties in our estimates using the bootstrap approach, the
      range of unicellular nitrogen fixation extended from 10% to 68% of the total
      annual rate of nitrogen fixation for all three diazotrophs. Furthermore, on a
      seasonal basis, the model demonstrated that unicellular diazotrophs fixed the
      majority (51%-97%) of nitrogen during winter and spring, whereas Trichodesmium
      dominated nitrogen fixation during summer and autumn (60%-96%). Sensitivity of
      the modeled rates to some parameters suggests that this unique attempt to
      quantify relative rates of nitrogen fixation by different diazotrophs may need to
      be reevaluated as additional information on cell size, variability in biomass and
      C:N, and growth characteristics of the different cyanobacterial diazotrophs
      become available.

PMID- 18043669
TI  - Differential interaction of Salmonella enterica serovars with lettuce cultivars
      and plant-microbe factors influencing the colonization efficiency.
AB  - The availability of knowledge of the route of infection and critical plant and
      microbe factors influencing the colonization efficiency of plants by human
      pathogenic bacteria is essential for the design of preventive strategies to
      maintain safe food. This research describes the differential interaction of human
      pathogenic Salmonella enterica with commercially available lettuce cultivars. The
      prevalence and degree of endophytic colonization of axenically grown lettuce by
      the S. enterica serovars revealed a significant serovar-cultivar interaction for
      the degree of colonization (S. enterica CFUs per g leaf), but not for the
      prevalence. The evaluated S. enterica serovars were each able to colonize soil
      grown lettuce epiphytically, but only S. enterica serovar Dublin was able to
      colonize the plants also endophytically. The number of S. enterica CFU per g of
      lettuce was negatively correlated to the species richness of the surface
      sterilized lettuce cultivars. A negative trend was observed for cultivars Cancan
      and Nelly, but not for cultivar Tamburo. Chemotaxis experiments revealed that S.
      enterica serovars actively move toward root exudates of lettuce cultivar Tamburo.
      Subsequent micro-array analysis identified genes of S. enterica serovar
      Typhimurium that were activated by the root exudates of cultivar Tamburo. A sugar
      like carbon source was correlated with chemotaxis, while also pathogenicity
      related genes were induced in presence of the root exudates. The latter revealed
      that S. enterica is conditioned for host cell attachment during chemotaxis by
      these root exudates. Finally, a tentative route of infection is described that
      includes plant-microbe factors, herewith enabling further design of preventive
      strategies.

PMID- 18043670
TI  - Soil eukaryotic functional diversity, a metatranscriptomic approach.
AB  - To appreciate the functional diversity of communities of soil eukaryotic micro
      organisms we evaluated an experimental approach based on the construction and
      screening of a cDNA library using polyadenylated mRNA extracted from a forest
      soil. Such a library contains genes that are expressed by each of the different
      organisms forming the community and represents its metatranscriptome. The
      diversity of the organisms that contributed to this library was evaluated by
      sequencing a portion of the 18S rDNA gene amplified from either soil DNA or
      reverse-transcribed RNA. More than 70% of the sequences were from fungi and
      unicellular eukaryotes (protists) while the other most represented group was the
      metazoa. Calculation of richness estimators suggested that more than 180 species
      could be present in the soil samples studied. Sequencing of 119 cDNA identified
      genes with no homologues in databases (32%) and genes coding proteins involved in
      different biochemical and cellular processes. Surprisingly, the taxonomic
      distribution of the cDNA and of the 18S rDNA genes did not coincide, with a
      marked under-representation of the protists among the cDNA. Specific genes from
      such an environmental cDNA library could be isolated by expression in a
      heterologous microbial host, Saccharomyces cerevisiae. This is illustrated by the
      functional complementation of a histidine auxotrophic yeast mutant by two cDNA
      originating possibly from an ascomycete and a basidiomycete fungal species. Study
      of the metatranscriptome has the potential to uncover adaptations of whole
      microbial communities to local environmental conditions. It also gives access to
      an abundant source of genes of biotechnological interest.

PMID- 18043671
TI  - The use of stable isotope probing to identify key iron-reducing microorganisms
      involved in anaerobic benzene degradation.
AB  - Here, we present a detailed functional and phylogenetic characterization of an
      iron-reducing enrichment culture maintained in our lab with benzene as sole
      carbon and energy source. We used DNA-stable isotope probing to identify microbes
      within the enrichment most active in the assimilation of (13)C-label. When
      (12)C(6)- and (13)C(6)-benzene were added as comparative substrates, marked
      differences in the quantitative buoyant density distribution became apparent
      especially for uncultured microbes within the Gram-positive Peptococcaceae,
      closely related to environmental clones retrieved from contaminated aquifers
      world wide and only distantly related to cultured representatives of the genus
      Thermincola. Prominent among the other constituents of the enrichment were
      uncultured Deltaproteobacteria, as well as members of the Actinobacteria.
      Although their presence within the enrichment seems to be stable they did not
      assimilate (13)C-label as significantly as the Clostridia within the time course
      of our experiment. We hypothesize that benzene degradation in our enrichment
      involves an unusual syntrophy, where members of the Clostridia primarily oxidize
      benzene. Electrons from the contaminant are both directly transferred to ferric
      iron by the primary oxidizers, but also partially shared with the
      Desulfobulbaceae as syntrophic partners. Alternatively, electrons may also be
      quantitatively transferred to the partners, which then reduce the ferric iron.
      Thus our results provide evidence for the importance of a novel clade of Gram
      positive iron-reducers in anaerobic benzene degradation, and a role of syntrophic
      interactions in this process. These findings shed a totally new light on the
      factors controlling benzene degradation in anaerobic contaminated environments.

PMID- 18043672
TI  - The diversity of the bacterial communities associated with the azooxanthellate
      hexacoral Cirrhipathes lutkeni.
AB  - This study examined the symbiotic microbiota of the hexacoral Cirrhipathes
      lutkeni using traditional plate culture, fluorescence in situ hybridization
      (FISH) and 16S rDNA characterization. FISH counts for the whole coral (holobiont)
      showed a major presence of gamma-Proteobacteria (22%) and Actinobacteria (19%),
      followed by alpha-Proteobacteria (14%), Firmicutes (9%), Cytophaga-Flavobacterium
      (7%), beta-Proteobacteria (6%) and Chloroflexi (2%). In contrast to the diversity
      observed by FISH, plate cultures were found to be selective for gamma
      Proteobacteria (22 cultures) with the exception of an Actinobacterium. The
      methods employed in this study detected 76% of all microbes estimated by DAPI
      staining of C. lutkeni homogenates. The absence of zooxanthellae in this
      particular hexacoral was confirmed by PCR and spectrophotometry using fresh
      tissue isolated from the holobiont. This is the first study describing the
      microbial associations of shallow-water hexacorallia, which opens further insight
      into coral microbial ecology and may enhance the search for novel natural
      products in the near future.

PMID- 18043674
TI  - My favorite topic...health.

PMID- 18043673
TI  - Ammonia oxidation and ammonia-oxidizing bacteria and archaea from estuaries with
      differing histories of hypoxia.
AB  - Nitrification, the oxidation of NH(4)(+) to NO(2)(-) and subsequently to NO(3)(
      ), plays a central role in the nitrogen cycle and is often a critical first step
      in nitrogen removal from estuarine and coastal environments. The first and rate
      limiting step in nitrification is catalyzed by the enzyme ammonia monooxygenase
      (AmoA). We evaluate the relationships between the abundance of ammonia-oxidizing
      archaea (AOA) and ammonia-oxidizing bacteria (AOB) amoA genes; potential
      nitrification rates and environmental variables to identify factors influencing
      AOA abundance and nitrifier activity in estuarine sediments. Our results showed
      that potential nitrification rates increased as abundance of AOA amoA increased.
      In contrast, there was no relationship between potential nitrification rates and
      AOB amoA abundance. This suggests that AOA are significant in estuarine nitrogen
      cycling. Surprisingly, more of the variability in potential nitrification rates
      was predicted by salinity and pore water sulfide than by dissolved oxygen
      history.

PMID- 18043675
TI  - How to manage refractory GERD.
AB  - Patients who are unresponsive to 4-8 weeks' treatment with PPIs twice daily might
      have so-called refractory GERD. The first investigation these patients should
      undergo is upper endoscopy to exclude a diagnosis of peptic ulcer disease or
      cancer and identify the presence of esophagitis. The presence of esophagitis in
      these patients is suggestive of a pill-induced injury, an autoimmune skin disease
      involving the esophagus, eosinophilic esophagitis or, less likely, a
      hypersecretory syndrome or a genotype that confers altered metabolism of PPIs.
      Refractory reflux syndromes associated with normal endoscopy findings are more
      problematic to diagnose and further testing may be required, including prolonged
      48 h pH testing, impedance measurements (for nonacid reflux), esophageal
      manometry and gastric function tests. For patients with refractory GERD who do
      not have esophagitis, possible etiologies include nocturnal gastric acid
      breakthrough, nonacid GER, missed GER or other diseases such as achalasia,
      gastroparesis or functional heartburn.

PMID- 18043676
TI  - Imaging and management of rectal cancer.
AB  - Local staging and management of rectal cancer has evolved during the past decade.
      Imaging modalities used for staging rectal cancer include CT, endoscopic
      ultrasound, pelvic phased-array coil MRI, endorectal MRI, and PET. Each modality
      has its strengths and limitations. Evidence supports the use of both endoscopic
      ultrasound and CT in staging rectal cancer. MRI is the only reliable tool for
      determining the status of the circumferential resection margin, which is
      important for the assessment of the risk of local recurrence.

PMID- 18043677
TI  - Minimal hepatic encephalopathy.
AB  - Minimal hepatic encephalopathy (MHE), formerly known as subclinical hepatic
      encephalopathy, is the mild cognitive impairment commonly seen in patients who
      have cirrhosis. Current understanding suggests that MHE forms part of the
      spectrum of hepatic encephalopathy, although this remains to be proven. Although
      traditionally viewed as having negligible clinical significance, MHE has a
      significant impact on quality of life. MHE often goes undiagnosed because in many
      patients there is no evidence of clinically overt signs of impaired cognition. In
      addition, the diagnostic criteria for MHE have not been standardized, which means
      that the exact characteristics of MHE remain in question. This Review focuses on
      the pathogenesis and neuropsychological findings (incorporating neuroimaging) of
      MHE, as well as the effect of MHE on quality of life and survival, and
      developments in treatment.

PMID- 18043678
TI  - Drug Insight: pharmacology and toxicity of thiopurine therapy in patients with
      IBD.
AB  - Thiopurines are frequently used for the treatment of IBD. The complex
      pharmacology, metabolism, mechanism of action and toxicity profile of these
      immunosuppressive drugs have now been partly elucidated. The activity of
      thiopurines is partly mediated by the metabolite 6-thioguanosine 5'-triphosphate,
      which inhibits the function of the small GTPase Rac1, leading to apoptosis of
      activated T cells, and influences the conjugation of T cells with antigen
      presenting cells. The activity of the enzyme thiopurine S-methyltransferase has a
      major influence on the bioavailability and toxicity of thiopurines, and several
      thiopurine metabolites might have adverse effects in patients. Myelotoxicity can
      be caused by grossly elevated levels of 6-thioguanine nucleotides, and elevated
      levels of 6-methylmercaptopurine ribonucleotides have been associated with
      hepatotoxicity. The sensitivity and specificity of these methylated metabolites
      for predicting thiopurine-induced liver enzyme abnormalities are, however, poor.
      6-Thioguanine has been suggested as an alternative to the classical thiopurines
      azathioprine and 6-mercaptopurine for the treatment of IBD, but there are
      concerns about its toxicity profile, especially with regard to the induction of
      nodular regenerative hyperplasia of the liver. Data now suggest that the
      induction of nodular regenerative hyperplasia of the liver during 6-thioguanine
      therapy might be dose-dependent or dependent on the level of 6-thioguanine
      nucleotides.

PMID- 18043679
TI  - A case of acute loss of vision as the presenting symptom of Crohn's disease.
AB  - BACKGROUND: An adolescent boy aged 17 years presented with sudden onset of visual
      impairment, which was rapidly diagnosed as bilateral anterior uveitis by an
      ophthalmologist. A systemic review noted episodes of nonbloody diarrhea, weight
      loss of 3 kg and a diminished appetite during the previous 10 months. The
      patient's family history revealed an older brother with Crohn's disease.
      INVESTIGATIONS: Visual acuity test, slit-lamp examination, ophthalmologic
      fundoscopy and endoscopic evaluation of the upper and lower gastrointestinal
      tract with biopsy. DIAGNOSIS: Multifocal Crohn's disease, involving the terminal
      ileum and cecum, in addition to the stomach and duodenum. MANAGEMENT: Treatment
      with topical corticosteroids, in the form of ophthalmic drops and oral budesonide
      ileal-release capsules. Once remission was achieved, it was maintained with
      mercaptopurine.

PMID- 18043680
TI  - Coronary heart disease in women: update 2008.
AB  - Coronary heart disease (CHD) remains the leading cause of mortality for US women,
      responsible for almost 250,000 deaths annually. Preventive heart-health
      behavioral changes by women and aggressive coronary risk reduction can decrease
      the number of women disabled and killed by CHD. Angina is the predominant initial
      and subsequent presentation of CHD in women; categorization of chest pain and
      risk stratification of women assume pivotal roles. A robust evidence-based
      algorithm can guide cardiovascular imaging techniques to evaluate women with
      suspected myocardial ischemia to detect those with worsened survival. Restricted
      functional capacity (<5 METs) is a consistent marker of worsened prognosis.
      Younger women have substantially higher mortality rates than men following
      myocardial infarction and coronary bypass surgery. Although these women have more
      comorbidity and risk factors, other issues including biological differences,
      treatment differences, and psychosocial factors require management strategies
      tailored to the unique needs of women.

PMID- 18043681
TI  - Emergency contraception update: a Canadian perspective.
AB  - Barriers to hormonal emergency contraceptive (EC) access in Canada and the United
      States led professional and lay groups to lobby for levonorgestrel (LNG) (PLAN B,
      Barr Pharmaceuticals, Pomona, New York) to be made available over-the-counter. In
      December 2000, British Columbia, Canada, granted EC prescriptive authority to
      pharmacists, followed by Quebec in December 2001 and Saskatchewan in September
      2003. In April 2005, Health Canada placed LNG on non-prescription, behind-the
      pharmacy-counter status with no age restriction. After much controversy, in
      August 2006, the Food and Drug Administration (FDA) approved over-the-counter
      access to LNG by adults in the United States. Results of our experience in Canada
      and recent information regarding mechanisms of action, effectiveness, adverse
      effects, and the effect of increased availability on reproductive health outcomes
      are presented here to help inform clinical practice.

PMID- 18043682
TI  - Post-marketing strategies for medicines.

PMID- 18043684
TI  - The polymorphisms Asn130Asp and Val174Ala in OATP1B1 and the CYP2C9 allele *3
      independently affect torsemide pharmacokinetics and pharmacodynamics.

PMID- 18043688
TI  - Blunting of the cardiovascular effect of aspirin by ibuprofen: what is the
      evidence?

PMID- 18043689
TI  - Methadone-induced QTc prolongation: is it due to stereoselective block of hERG or
      to inappropriate QT interval correction?

PMID- 18043690
TI  - Thorough QT study with recommended and supratherapeutic doses of tolterodine.

PMID- 18043691
TI  - Development of CYP2D6 and CYP3A4 in the first year of life.

PMID- 18043692
TI  - The implications of population admixture in race-based drug prescription.

PMID- 18043693
TI  - No influence of ABCB1 haplotypes on methadone dosage requirement.

PMID- 18043696
TI  - Design of the "Thorough QT Study".

PMID- 18043697
TI  - Upregulation of multidrug resistance-associated protein 3 by acetaminophen may
      help to increase its own clearance.

PMID- 18043698
TI  - Processed EEG (bispectral index) is not appropriate for characterizing opioid
      sedation.

PMID- 18043699
TI  - Neuropeptide Y polymorphism significantly magnifies diabetes and cardiovascular
      disease risk in obesity: the Hoorn Study.
AB  - The leucine7 to proline7 (Leu7Pro) polymorphism in preproneuropeptide Y
      (preproNPY) has been associated with accelerated atherosclerosis and type II
      diabetes, both of which are obesity-related diseases. The current study evaluated
      the impact of obesity on the disease risk linked to the Leu7Pro polymorphism of
      preproNPY in 393 elderly subjects. In 6 years follow-up, the polymorphism alone
      did not change the risk for abnormal glucose regulation, while obesity was
      associated with a significant 3-fold risk (odds ratio (OR) 2.95; 95% confidence
      interval (CI) 1.81-4.81, P<0.001) and the Leu7Pro polymorphism-obesity
      interaction, with a remarkable 12-fold risk (OR 12.33; 95% CI 1.18-128.35,
      P<0.05). The Leu7Pro polymorphism modified significantly the 10-year incidence of
      cardiovascular events, causing a 7.6-fold increase in the hazard ratio (HR 7.58;
      95% CI 2.87-20.03, P<0.001) in the obese but not in the nonobese subjects. The
      results indicate that obesity may be a pivotal factor in multiplying the disease
      risk associated with the Leu7Pro polymorphism in preproNPY.

PMID- 18043700
TI  - Multivitamin supplementation improves nutritional status and bone quality in aged
      care residents.
AB  - OBJECTIVES: To assess the effectiveness of a multivitamin (MV) tablet on
      nutritional status, quantitative heel ultrasound (QUS), mobility, muscle strength
      and falls. The design comprised two groups matched on mobility levels, randomized
      to receive a daily MV or placebo (P) tablet for 6 months. The setting was an
      Australian residential care facility. SUBJECTS: A total of 92 aged care
      residents. Serum micronutrients, body weight, QUS, rate of falls, hand grip
      strength, and the timed up and go test were assessed at baseline and 6 months.
      RESULTS: A total of 49 participants consumed a MV and 43, a matched P for 6
      months. There was a greater increase in the MV vs P group for serum 25(OH)D (mean
      difference+/-standard error, 33.4+/-2.6 nmol l(-1)), folate (13.4+/-2.8 nmol l(
      1)), and vitamin B12 (178.0+/-40.3 pmol l(-1)) (all P<0.001). Adequate 25(OH)D
      concentrations (> or =50 nmol l(-1)) were found among 77% of participants in the
      MV group vs 10% taking P (P<0.001). Adjusting for baseline levels, the increase
      in QUS was greater in the MV vs P group (3.0+/-2.0 dB MHz(-1) vs -2.9+/-2.1 dB
      MHz(-1), respectively, P=0.041). There was a trend towards a 63% lower mean
      number of falls in the MV vs P group (0.3+/-0.1 falls vs 0.8+/-0.3 falls,
      P=0.078). CONCLUSIONS: MV supplementation raised serum vitamin B12 and folate
      concentrations and increased serum 25(OH)D, which was accompanied by an apparent
      positive effect on bone density. We also found a trend towards a reduction in
      falls and this could contribute to a reduction in fractures.

PMID- 18043701
TI  - Vitamin A deficiency among Brazilian school-aged children in a healthy child
      service.
AB  - BACKGROUND/OBJECTIVES: Vitamin A deficiency (VAD) is a world public health
      problem contributing to the increase in childhood morbidity and mortality in
      developing countries and severe deficiency of vitamin A may lead to xerophthalmia
      and blindness. The objective of this study was to determine the prevalence of VAD
      among Brazilian school-aged children attended at a primary health unit and to
      verify if some considered risk factor was associated with VAD in this group.
      SUBJECTS/METHODS: A descriptive prospective transverse study was conducted on 103
      randomly selected children. A total of 54 boys and 49 girls aged 5.5-11 years had
      the relative dose-response (RDR) test performed on. Possible ocular alterations
      related to vitamin A and the status of anemia, serum zinc, some acute-phase
      proteins, and anthropometric situation were determinate by an analytic design.
      RESULTS: No child presented xerophthalmia. Serum retinol values lower than 1.05
      and 0.7 micromol l(-1), respectively were found in 26.2 and 5.8% of the children.
      The prevalence of hypovitaminosis detected by RDR test was 20.4%. The following
      variables and their relationship with VAD were evaluated: sex (P=0.33; 95%
      confidence interval 0.61-4.34), weight and height (P> or =0.5), hemoglobin
      (P=0.15), C-reactive protein (P=0.56; 95% confidence interval 0.75-18.26), alpha
      1-acid-glycoprotein (P=0.56; 95% confidence interval 0.15-15.42) and serum zinc
      (P=0.31). None of these variables was related to VAD. CONCLUSIONS: In this
      population, the prevalence of VAD detected could be considered a public health
      problem. School-aged children can be considered at risk for VAD mainly of a
      subclinical level, even without some associated risk factors.

PMID- 18043702
TI  - Does early enteral feeding of very low birth weight infants increase the risk of
      necrotizing enterocolitis?
AB  - BACKGROUND/OBJECTIVE: In this retrospective study, we intended to test whether
      early enteral feeding (EEF) of very low birth weight (VLBW) preterm babies
      increases the risk of necrotizing enterocolitis (NEC) or not. SUBJECTS AND
      METHODS: Overall, 297 VLBW preterm babies admitted to the neonatal intensive care
      unit (NICU) between April 2003 and April 2006 were included. The study consisted
      of two periods: the first period was between April 2003 and October 2004, when
      babies were not fed enterally until they were extubated (167 preterm VLBWs). The
      second period was between November 2004 and April 2006, when babies were fed even
      when they were intubated, starting preferably on the first day of life (130
      preterm VLBWs). Criteria for withholding enteral feeding in both periods were
      hypotension necessitating vasopressor agent use, abdominal distention, abdominal
      tenderness and suspected or proven NEC. Possible risk factors for NEC were also
      recorded. RESULTS: The overall incidence of NEC in VLBW preterm babies was 6.7%
      and did not differ between the two study periods: 7.2% in the late and 6.2% in
      the EEF regimens. On logistic regression analysis, the most important risk
      factors associated with NEC were sepsis (P<0.001) and blood culture positivity
      (P<0.001). The average daily weight gain was significantly higher in the early
      fed babies (P=0.011). CONCLUSIONS: The EEF of VLBW preterm babies does not
      increase the risk of NEC. Increased daily weight gain is an important reason to
      feed these babies earlier.

PMID- 18043703
TI  - Skipping breakfast, alcohol consumption and physical inactivity as risk factors
      for overweight and obesity in adolescents: results of the E-MOVO project.
AB  - OBJECTIVE/BACKGROUND: To investigate the association between skipping breakfast,
      alcohol consumption and physical inactivity with overweight and obesity in
      adolescents. The design comprises cross-sectional electronic health survey (E
      MOVO). SUBJECTS/METHODS: Over 35 000 Dutch adolescents in grade 2 (13-14 years of
      age) and grade 4 (15-16 years of age) of secondary educational schools were
      recruited by seven community health services. Analyses were performed on 25 176
      adolescents. Body mass index was calculated from self-reported body weight and
      height. Frequency of skipping breakfast per week, amount of alcoholic drinks
      consumed per occasion, and numbers of physical active days per week were
      considered as determinants for overweight and obesity. RESULTS: In grade 2,
      adjusted odds ratios for the association with overweight were 2.17 (95% CI: 1.66
      2.85) for skipping breakfast, 1.86 (1.36-2.55) for alcohol consumption and 1.73
      (1.19-2.51) for physical inactivity. Statistically significant associations with
      overweight were also found in grade 4. In grade 2, dose-response relations (P for
      trend <0.05) were present between all risk factors and overweight. In a
      multivariate model containing all risk factors, breakfast skipping showed the
      strongest relation with overweight (OR 1.68, 95% CI 1.43-1.97 for grade 2, OR
      1.32 95% CI 1.14-1.54 for grade 4) and obesity. CONCLUSIONS: Skipping breakfast,
      alcohol consumption and physical inactivity were associated with overweight in
      second and fourth grade adolescents. The associations were strongest for younger
      adolescents. The most important risk factor for overweight and obesity was
      skipping breakfast.

PMID- 18043707
TI  - Heterotrimeric G protein activation by G-protein-coupled receptors.
AB  - Heterotrimeric G proteins have a crucial role as molecular switches in signal
      transduction pathways mediated by G-protein-coupled receptors. Extracellular
      stimuli activate these receptors, which then catalyse GTP-GDP exchange on the G
      protein alpha-subunit. The complex series of interactions and conformational
      changes that connect agonist binding to G protein activation raise various
      interesting questions about the structure, biomechanics, kinetics and specificity
      of signal transduction across the plasma membrane.

PMID- 18043709
TI  - Multiple variants of the DRD3, but not BDNF gene, influence age-at-onset of
      schizophrenia.

PMID- 18043710
TI  - KATP channels confer survival advantage in cocaine overdose.

PMID- 18043711
TI  - Variants in PDE11A and PDE1A are not associated with citalopram response.

PMID- 18043712
TI  - No evidence of association between a functional polymorphism in the MTHFR gene
      and childhood-onset mood disorders.

PMID- 18043713
TI  - Dissecting the molecular mechanisms in craniofrontonasal syndrome: differential
      mRNA expression of mutant EFNB1 and the cellular mosaic.
AB  - Craniofrontonasal syndrome (CFNS) is an X-linked malformation syndrome with
      variable phenotype that is caused by mutations in the ephrin-B1 gene (EFNB1).
      Over 50% of EFNB1 mutations result in premature termination codons that may
      elicit mRNA degradation by the nonsense-mediated decay pathway. To assess the
      effects of various mutations at the transcript level, expression of EFNB1 mRNA
      was studied by RT-PCR in fibroblast cultures established from CFNS female
      patients. Compared to the wild-type and two missense mutation alleles, severe
      depletion of transcripts was observed for mutant alleles harbouring either splice
      site mutation c.407-2A>T at the exon 2/3 boundary or frameshift mutation
      c.377_384delTCAAGAAG in exon 2. In contrast, escape from mRNA decay was observed
      for mutation c.614_615delCT, which generates a premature termination codon close
      to the 3'-end of the penultimate exon 4 disobeying the '50-55 bp' rule. These
      results suggest differential degradation of mutant EFNB1 transcripts by the
      nonsense-mediated mRNA decay pathway. Although the clinical phenotypes of the
      patients were not highly suggestive of a phenotype-genotype correlation, the two
      female patients were diagnosed with diaphragmatic hernia harbouring putative
      ephrin-B1 truncating mutations. Previously, disease manifestation in heterozygous
      females had been attributed mainly to cellular interference of divergent cell
      populations expressing wild-type or mutant EFNB1, depending on the pattern of X
      inactivation. Upon clonal expansion of patient cells with either the wild-type or
      mutant EFNB1 on the active X-chromosome, we were able to separate mutant and wild
      type EFNB1-expressing cells in vitro, further supporting the concept of cellular
      interference in CFNS.

PMID- 18043714
TI  - Identification of a nonsense mutation in the very low-density lipoprotein
      receptor gene (VLDLR) in an Iranian family with dysequilibrium syndrome.
AB  - We have investigated a consanguineous Iranian family with eight patients who
      suffer from mental retardation, disturbed equilibrium, walking disability,
      strabismus and short stature. By autozygosity mapping we identified one region
      with a significant LOD score on chromosome 9(p24.2-24.3). The interval contains
      the VLDLR gene, which codes for the very low-density lipoprotein receptor. This
      protein is part of the reelin signalling pathway, which is involved in neuroblast
      migration in the cerebral cortex and cerebellum. A homozygous deletion
      encompassing VLDLR has previously been found to cause a syndrome of cerebellar
      ataxia and mental retardation associated with cerebellar hypoplasia in the
      Hutterite population known as dysequilibrium syndrome (DES). The reported
      deletion however, contains an additional brain expressed gene of unknown
      function, whose involvement in the aetiology of the phenotype could so far not be
      excluded. We screened the coding region of VLDLR for mutations in our patients
      and found a homozygous c.1342C>T nucleotide substitution, which leads to a
      premature stop codon in exon 10. This is the first report of a mutation in
      patients with DES that affects VLDLR exclusively, confirming the central role of
      the very low-density lipoprotein receptor in the aetiology of this condition.

PMID- 18043715
TI  - Low prevalence of APP duplications in Swedish and Finnish patients with early
      onset Alzheimer's disease.
AB  - Familial early-onset Alzheimer's disease with cerebral amyloid angiopathy
      (EOAD/CAA) was recently associated with duplications of the gene for the amyloid
      beta precursor protein (APP). In this study, we have screened for duplications of
      APP in patients with EOAD from Sweden and Finland. Seventy-five individuals from
      families with EOAD and 66 individuals with EOAD without known familial
      inheritance were screened by quantitative PCR. On the basis of the initial
      results, a portion of the samples was also investigated with quantitative
      multiplex PCR. No duplications of APP were identified, whereby we conclude that
      this is not a common cause of EOAD in the Swedish and Finnish populations, at
      least not in our collection of families and cases.

PMID- 18043716
TI  - The ACTN3 R577X nonsense allele is under-represented in elite-level strength
      athletes.
AB  - Previous reports have shown a lower proportion of the ACTN3 X/X genotype (R577X
      nonsense polymorphism) in sprint-related athletes compared to the general
      population, possibly attributed to impairment of muscle function related to alpha
      actinin-3 deficiency. In the present study, we examined the frequency of the X/X
      genotype in both Black and White elite-level bodybuilders and strength athletes
      in comparison to the general population. A reference population of 668 Whites
      (363 men and 305 women) and 208 Blacks (98 men and 110 women) was genotyped for
      the ACTN3 R577X polymorphism. Strength athletes (52 white and 23 black; 4 women)
      consisting predominantly of world class and locally competitive bodybuilders, and
      elite powerlifters were recruited and similarly genotyped. Significantly lower
      X/X genotype frequencies were observed in the athletes (6.7%) vs controls (16.3%;
      P=0.005). The X/X genotype was significantly lower in White athletes (9.7%) vs
      controls (19.9%; P=0.018). No black athletes (0%) were observed with the X/X
      genotype, though this finding only approached statistical significance vs
      controls (4.8%; P=0.10). The results indicate that the ACTN3 R577X nonsense
      allele (X) is under-represented in elite strength athletes, consistent with
      previous reports indicating that alpha-actinin-3 deficiency appears to impair
      muscle performance.

PMID- 18043717
TI  - Population genetic diversity of the NAT2 gene supports a role of acetylation in
      human adaptation to farming in Central Asia.
AB  - The arylamine N-acetyltransferase 2 (NAT2) enzyme detoxifies a wide spectrum of
      naturally occurring xenobiotics including carcinogens and drugs. Variation at the
      NAT2 gene has been linked to the human acetylation capacity, either 'slow' or
      'fast', which modifies susceptibility to cancer and adverse drug reactions. We
      investigated the possible influence of natural selection in shaping the
      acetylation phenotype and the NAT2 gene variability in six Central Asian
      populations, who are either long-term sedentary agriculturalists (two Tajik
      populations), recent sedentary agriculturalists (Kazakhs, Uzbeks) or nomad
      pastoralists (two Kirghiz populations). To this end, we sequenced the entire NAT2
      coding exon, as well as genotyping nine intergenic SNPs covering a 200-kb region.
      Our results revealed that the two Tajik populations exhibited significantly
      higher proportions of slow acetylators than the nomadic populations. In addition,
      sequence-based neutrality tests yielded significantly positive values in Central
      Asian populations following an agriculturalist lifestyle, due to an excess of
      haplotypes at intermediate frequencies. Taken together, our data suggest that
      balancing selection, and/or directional selection on standing low-frequency
      alleles, have shaped NAT2 genetic diversity and the human acetylation phenotype
      in Central Asian agriculturalists. These results further support the hypothesis
      that a major transition in human lifestyle, such as the emergence of farming has
      dramatically changed human chemical environments and the selective pressures they
      imposed.

PMID- 18043718
TI  - ALS predisposition modifiers: knock NOX, who's there? SOD1 mice still are.

PMID- 18043719
TI  - Look before you leap. Carrier screening for type 1 Gaucher disease: difficult
      questions.

PMID- 18043720
TI  - The novel hyperekplexia allele GLRA1(S267N) affects the ethanol site of the
      glycine receptor.
AB  - Mutations in the GLRA1 gene, which encodes the alpha1-subunit of the inhibitory
      glycine receptor (GlyR), are the underlying causes in the majority of cases of
      hereditary startle disease (OMIM no. 149400). GlyRs are modulated by alcohols and
      volatile anesthetics, where a specific amino acid at position 267 has been
      implicated in receptor modulation. We describe a hyperekplexia family carrying
      the novel dominant missense allele GLRA1(S267N), that affects agonist responses
      and ethanol modulation of the mutant receptor. This study implies that a disease
      related receptor allele carries the potential to alter drug responses in affected
      patients.

PMID- 18043721
TI  - Instability of expanded CAG/CAA repeats in spinocerebellar ataxia type 17.
AB  - Trinucleotide repeat expansions are dynamic mutations causing many neurological
      disorders, and their instability is influenced by multiple factors. Repeat
      configuration seems particularly important, and pure repeats are thought to be
      more unstable than interrupted repeats. But direct evidence is still lacking.
      Here, we presented strong support for this hypothesis from our studies on
      spinocerebellar ataxia type 17 (SCA17). SCA17 is a typical polyglutamine disease
      caused by CAG repeat expansion in TBP (TATA binding protein), and is unique in
      that the pure expanded polyglutamine tract is coded by either a simple
      configuration with long stretches of pure CAGs or a complex configuration
      containing CAA interruptions. By small pool PCR (SP-PCR) analysis of blood DNA
      from SCA17 patients of distinct racial backgrounds, we quantitatively assessed
      the instability of these two types of expanded alleles coding similar length of
      polyglutamine expansion. Mutation frequency in patients harboring pure CAG
      repeats is 2-3 folds of those with CAA interruptions. Interestingly, the pure CAG
      repeats showed both expansion and deletion while the interrupted repeats
      exhibited mostly deletion at a significantly lower frequency. These data strongly
      suggest that repeat configuration is a critical determinant for instability, and
      CAA interruptions might serve as a limiting element for further expansion of CAG
      repeats in SCA17 locus, suggesting a molecular basis for lack of anticipation in
      SCA17 families with interrupted CAG expansion.

PMID- 18043722
TI  - Treating substance abuse in primary care: a demonstration project.
AB  - PURPOSE: The purpose of this project was to implement the delivery of a full
      range of substance abuse services in a primary care setting. Implementation and
      logistical issues including confidentiality and communication are discussed. The
      delivery of services, types of patients, and contextual and policy factors that
      influenced project implementation are described. CONTEXT: Substance use disorders
      are associated with significant morbidity and mortality worldwide. Patients with
      alcohol/drug problems frequently present in primary care. Effective and brief
      treatments are available and recommended for primary care but infrequently
      implemented. Institutional and provider barriers to implementation have been
      identified. DATA SOURCE: Project documentation, data from the patient tracking
      system, and clinical case notes were used for description and analyses.
      CONCLUSION: Addressing substance abuse problems in primary care is important.
      Behavioral health professionals with training in substance abuse can provide a
      range of services that are likely to enhance the quality and quantity of care
      available to patients. Although contextual factors needed to be addressed,
      integration of services was manageable and seemed acceptable to both providers
      and patients in this project.

PMID- 18043723
TI  - The challenges of joint working: lessons from the Supporting People Health Pilot
      evaluation.
AB  - PURPOSE: This paper reports the findings of the evaluation of the Supporting
      People Health Pilots programme, which was established to demonstrate the policy
      links between housing support services and health and social care services by
      encouraging the development of integrated services. The paper highlights the
      challenges of working across housing, health and social care boundaries. METHOD:
      THE EVALUATION OF THE SIX HEALTH PILOTS RESTED ON TWO MAIN SOURCES OF DATA
      COLLECTION: Quarterly Project Evaluation Reports collected process data as well
      as reporting progress against aims and objectives. Semi-structured interviews
      conducted across all key professional stakeholder groups and agencies and with
      people who used services-explored their experiences of these new services.
      RESULTS: THE ABILITY OF PILOTS TO WORK ACROSS ORGANISATIONAL BOUNDARIES TO
      ACHIEVE THEIR AIMS AND OBJECTIVES WAS ASSOCIATED NOT ONLY WITH AGENCIES SHARING
      AN UNDERSTANDING OF THE PURPOSE OF THE JOINT VENTURE, A HISTORY OF JOINT WORKING
      AND CLEAR AND EFFICIENT GOVERNANCE ARRANGEMENTS BUT ON TWO OTHER CHARACTERISTICS:
      the extent and nature of statutory sector participation and, whether or not the
      service is defined by a history of voluntary sector involvement. In particular
      the pilots demonstrated how voluntary sector agencies appeared to be less
      constrained by organisational priorities and professional agenda and more able to
      respond flexibly to meet the complex needs of individuals. CONCLUSION AND
      DISCUSSION: The pilots demonstrate that integrating services to support people
      with complex needs works best when the service is determined by the
      characteristics of those who use the service rather than pre-existing
      organisational structures.

PMID- 18043724
TI  - Integrated inspection of services for people with learning disabilities in
      Scotland: the way forward?
AB  - PURPOSE: The article summarises the process and the results of the first,
      integrated inspection of managed care services for people with learning
      disabilities in Scotland. The multi-agency model used was developed to be
      congruent with the existing performance inspection models, used by single agency
      inspection. The inspection activities and main outcomes are described, and
      suggestions are made for improvements. CONTEXT OF CASE: In 2006 an inspection
      model was devised to assess the quality of health, social services and education
      services for people with learning disabilities in one geographical area of
      Scotland, as a precursor to a programme of inspections nationally. The first
      joint, integrated inspection of all services for people with learning
      disabilities in Scotland took place in June 2006, and the report was published in
      March 2007. This was the first multi-agency inspection of its kind in the UK, and
      the first to involve carers and people with learning disabilities on the
      inspection team. DATA SOURCES: A number of data sources were used to check
      existing practice against agreed Quality Outcome indicators. Primary sources of
      data were social work records, health records, education records, staff surveys,
      carer surveys, interviews with staff, family carers and people with learning
      disabilities, and self evaluations completed by the services being inspected.
      Eleven different domains, each with sub-indicators were investigated. CASE
      DESCRIPTION: This paper summarises the process of an integrated, multi-agency
      inspection, how the inspection activities were conducted and the main findings of
      this inspection. Practical improvements to the process are suggested, and these
      may be of use to other services and inspectorates. CONCLUSIONS AND DISCUSSION:
      The integrated inspection was a qualified success. Most major objectives were
      achieved. The sharing of data amongst inspection agencies, establishing the level
      of commitment to integrated inspection and conducting multiple, integrated
      inspections nationally in a reasonable timescale are the main barriers remaining.
      The data were collected in an innovative way during this inspection, to make the
      analysis directly relevant to services, by providing domain specific and area
      specific details about how well local needs are being met. The lessons from this
      integrated inspection may be of interest to other practitioners in the UK and
      beyond, both in terms of process and outcomes.

PMID- 18043725
TI  - Attending unintended transformations of health care infrastructure.
AB  - INTRODUCTION: Western health care is under pressure from growing demands on
      quality and efficiency. The development and implementation of information
      technology, IT is a key mean of health care authorities to improve on health care
      infrastructure. THEORY AND METHODS: Against a background of theories on human
      computer interaction and IT-mediated communication, different empirical studies
      of IT implementation in health care are analyzed. The outcome is an analytical
      discernment between different relations of communication and levels of
      interaction with IT in health care infrastructure. These relations and levels are
      synthesized into a framework for identifying tensions and potential problems in
      the mediation of health care with the IT system. These problems are also known as
      unexpected adverse consequences, UACs, from IT implementation into clinical
      health care practices. RESULTS: This paper develops a conceptual framework for
      addressing transformations of communication and workflow in health care as a
      result of implementing IT. CONCLUSION AND DISCUSSION: The purpose of the
      conceptual framework is to support the attention to and continuous screening for
      errors and unintended consequences of IT implementation into health care
      practices and outcomes.

PMID- 18043726
TI  - Telehomecare technology across sectors: claims of jurisdiction and emerging
      controversies.
AB  - PURPOSE: The purpose of this study was to explore and identify inter
      organisational and inter-professional controversies that emerge when telehomecare
      technology is implemented across healthcare sectors. THEORY: A combined inter
      organisational and inter-professional perspective constitutes the conceptual
      framework for this study. METHODS: The case study approach was applied as the
      overall methodology of the study. A triangulation of data collection techniques
      was used in order to provide multiple sources of evidence for exploring and
      identifying controversies (documents, participant observation, qualitative
      interviews, focus group interviews). FINDINGS: During the design and
      implementation phases of a telehomecare system, several types of controversies
      emerged as part of the inter-organisational and inter-professional agenda. These
      controversies involved competing claims of jurisdiction, controversies over
      knowledge technologies, or differences in network visions and network
      architecture. DISCUSSION AND CONCLUSIONS: The identification of such
      controversies and differences in the design and implementation process of the
      concept of home hospitalisation for heart patients by means of telehomecare
      technology can contribute to the uncovering of new knowledge. These issues should
      be taken into account when initiating a telehomecare project and implementing
      telehomecare technology. Technology in a network and across inter-professional
      relations poses a challenge to this new field. There is a particular need to
      precisely define the claims of jurisdiction, and the accompanying controversies
      that can arise related to knowledge technologies, network visions and network
      architecture.

PMID- 18043727
TI  - Changing Mad2 levels affects chromosome segregation and spindle assembly
      checkpoint control in female mouse meiosis I.
AB  - The spindle assembly checkpoint (SAC) ensures correct separation of sister
      chromatids in somatic cells and provokes a cell cycle arrest in metaphase if one
      chromatid is not correctly attached to the bipolar spindle. Prolonged metaphase
      arrest due to overexpression of Mad2 has been shown to be deleterious to the
      ensuing anaphase, leading to the generation of aneuploidies and tumorigenesis.
      Additionally, some SAC components are essential for correct timing of
      prometaphase. In meiosis, we and others have shown previously that the Mad2
      dependent SAC is functional during the first meiotic division in mouse oocytes.
      Expression of a dominant-negative form of Mad2 interferes with the SAC in
      metaphase I, and a knock-down approach using RNA interference accelerates
      anaphase onset in meiosis I. To prove unambigiously the importance of SAC control
      for mammalian female meiosis I we analyzed oocyte maturation in Mad2 heterozygote
      mice, and in oocytes overexpressing a GFP-tagged version of Mad2. In this study
      we show for the first time that loss of one Mad2 allele, as well as
      overexpression of Mad2 lead to chromosome missegregation events in meiosis I, and
      therefore the generation of aneuploid metaphase II oocytes. Furthermore, SAC
      control is impaired in mad2+/- oocytes, also leading to the generation of
      aneuploidies in meiosis I.

PMID- 18043728
TI  - Haplotypes in the complement factor H (CFH) gene: associations with drusen and
      advanced age-related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration (AMD), the leading cause of
      blindness in the Western world, is a complex disease that affects people over 50
      years old. The complement factor H (CFH) gene has been repeatedly shown to be a
      major factor in determining susceptibility to the advanced form of the condition.
      We aimed to better understand the functional role of this gene in the AMD disease
      process and assess whether it is associated with earlier forms of the disease.
      METHODOLOGY/PRINCIPAL FINDINGS: WE genotyped SNPS at the cfh gene locus in three
      independent populations with AMD: (a) extended families where at least 3 family
      members had AMD; (b) sporadic cases of advanced AMD and (c) cases from the Age
      Related Eye Disease Study (AREDS). We investigated polymorphisms and haplotypes
      in and around the CFH gene to assess their role in AMD. CFH is associated with
      early/intermediate and advanced AMD in both familial and sporadic cases. In our
      populations, the CFH SNP, rs2274700, is most strongly associated with AMD and
      when incorporated into a haplotype with the Y402H SNP and rs1061147, the
      strongest association is observed (p<10(-9)). CONCLUSIONS/SIGNIFICANCE: Our
      results, reproduced in three populations that represent the spectrum of AMD
      cases, provide evidence that the CFH gene is associated with drusen as well as
      with advanced AMD. We also identified novel susceptibility and protective
      haplotypes in the AMD populations.

PMID- 18043729
TI  - Epigenetic regulation of histone H3 serine 10 phosphorylation status by HCF-1
      proteins in C. elegans and mammalian cells.
AB  - BACKGROUND: The human herpes simplex virus (HSV) host cell factor HCF-1 is a
      transcriptional coregulator that associates with both histone methyl- and
      acetyltransferases, and a histone deacetylase and regulates cell proliferation
      and division. In HSV-infected cells, HCF-1 associates with the viral protein VP16
      to promote formation of a multiprotein-DNA transcriptional activator complex. The
      ability of HCF proteins to stabilize this VP16-induced complex has been conserved
      in diverse animal species including Drosophila melanogaster and Caenorhabditis
      elegans suggesting that VP16 targets a conserved cellular function of HCF-1.
      METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of HCF proteins in animal
      development, we have characterized the effects of loss of the HCF-1 homolog in C.
      elegans, called Ce HCF-1. Two large hcf-1 deletion mutants (pk924 and ok559) are
      viable but display reduced fertility. Loss of Ce HCF-1 protein at reduced
      temperatures (e.g., 12 degrees C), however, leads to a high incidence of
      embryonic lethality and early embryonic mitotic and cytokinetic defects
      reminiscent of mammalian cell-division defects upon loss of HCF-1 function. Even
      when viable, however, at normal temperature, mutant embryos display reduced
      levels of phospho-histone H3 serine 10 (H3S10P), a modification implicated in
      both transcriptional and mitotic regulation. Mammalian cells with defective HCF-1
      also display defects in mitotic H3S10P status. CONCLUSIONS/SIGNIFICANCE: These
      results suggest that HCF-1 proteins possess conserved roles in the regulation of
      cell division and mitotic histone phosphorylation.

PMID- 18043730
TI  - Induction of human immunodeficiency virus (HIV-1) envelope specific cell-mediated
      immunity by a non-homologous synthetic peptide.
AB  - BACKGROUND: Cell mediated immunity, including efficient CTL response, is required
      to prevent HIV-1 from cell-to-cell transmission. In previous investigations, we
      have shown that B1 peptide derived by Fourier transformation of HIV-1 primary
      structures and sharing no sequence homology with the parent proteins was able to
      generate antiserum which recognizes envelope and Tat proteins. Here we have
      investigated cellular immune response towards a novel non-homologous peptide,
      referred to as cA1 peptide. METHODOLOGY/PRINCIPAL FINDINGS: The 20 amino acid
      sequence of cA1 peptide was predicted using the notion of peptide hydropathic
      properties; the peptide is encoded by the complementary anti-sense DNA strand to
      the sense strand of previously described non-homologous A1 peptide. In this
      report we demonstrate that the cA1 peptide can be a target for major
      histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes in
      HIV-1-infected or envelope-immunized individuals. The cA1 peptide is recognized
      in association with different MHC class I allotypes and could prime in vitro
      CTLs, derived from gp160-immunized individuals capable to recognize virus
      variants. CONCLUSIONS/SIGNIFICANCE: For the first time a theoretically designed
      immunogen involved in broad-based cell-immune memory activation is described. Our
      findings may thus contribute to the advance in vaccine research by describing a
      novel strategy to develop a synthetic AIDS vaccine.

PMID- 18043731
TI  - Individual assessment of arteriosclerosis by empiric clinical profiling.
AB  - BACKGROUND: Arteriosclerosis is a common cause of chronic morbidity and
      mortality. Myocardial infarction, stroke or other cardiovascular events identify
      vulnerable patients who suffer from symptomatic arteriosclerosis. Biomarkers to
      identify vulnerable patients before cardiovascular events occur are warranted to
      improve care for affected individuals. We tested how accurately basic clinical
      data can describe and assess the activity of arteriosclerosis in the individual
      patient. METHODOLOGY/PRINCIPAL FINDINGS: 269 in-patients who were treated for
      various conditions at the department of general medicine of an academic tertiary
      care center were included in a cross-sectional study. Personal history and
      clinical examination were obtained. When paraclinical tests were performed, the
      results were added to the dataset. The numerical variables in the clinical
      examination were statistically compared between patients with proven symptomatic
      arteriosclerosis (n = 100) and patients who had never experienced cardiovascular
      events in the past (n = 110). 25 variables were different between these two
      patient groups and contributed to the disease activity score. The percentile
      distribution of these variables defined the empiric clinical profile.
      Anthropometric data, signs of arterial, cardiac and renal disease, systemic
      inflammation and health economics formed the major categories of the empiric
      clinical profile that described an individual patient's disease activity. The
      area under the curve of the receiver operating curve for symptomatic
      arteriosclerosis was 0.891 (95% CI 0.799-0.983) for the novel disease activity
      score compared to 0.684 (95% CI 0.600-0.769) for the 10-year risk calculated
      according to the Framingham score. In patients suffering from symptomatic
      arteriosclerosis, the disease activity score deteriorated more rapidly after two
      years of follow-up (from 1.25 to 1.48, P = 0.005) compared to age- and sex
      matched individuals free of cardiovascular events (from 1.09 to 1.19, P = 0.125).
      CONCLUSIONS/SIGNIFICANCE: Empiric clinical profiling and the disease activity
      score that are based on accessible, available and affordable clinical data are
      valid markers for symptomatic arteriosclerosis.

PMID- 18043732
TI  - Proteomic shifts in embryonic stem cells with gene dose modifications suggest the
      presence of balancer proteins in protein regulatory networks.
AB  - Large numbers of protein expression changes are usually observed in mouse models
      for neurodegenerative diseases, even when only a single gene was mutated in each
      case. To study the effect of gene dose alterations on the cellular proteome, we
      carried out a proteomic investigation on murine embryonic stem cells that either
      overexpressed individual genes or displayed aneuploidy over a genomic region
      encompassing 14 genes. The number of variant proteins detected per cell line
      ranged between 70 and 110, and did not correlate with the number of modified
      genes. In cell lines with single gene mutations, up and down-regulated proteins
      were always in balance in comparison to parental cell lines regarding number as
      well as concentration of differentially expressed proteins. In contrast, dose
      alteration of 14 genes resulted in an unequal number of up and down-regulated
      proteins, though the balance was kept at the level of protein concentration. We
      propose that the observed protein changes might partially be explained by a
      proteomic network response. Hence, we hypothesize the existence of a class of
      "balancer" proteins within the proteomic network, defined as proteins that buffer
      or cushion a system, and thus oppose multiple system disturbances. Through
      database queries and resilience analysis of the protein interaction network, we
      found that potential balancer proteins are of high cellular abundance, possess a
      low number of direct interaction partners, and show great allelic variation.
      Moreover, balancer proteins contribute more heavily to the network entropy, and
      thus are of high importance in terms of system resilience. We propose that the
      "elasticity" of the proteomic regulatory network mediated by balancer proteins
      may compensate for changes that occur under diseased conditions.

PMID- 18043733
TI  - A biological model for influenza transmission: pandemic planning implications of
      asymptomatic infection and immunity.
AB  - BACKGROUND: The clinical attack rate of influenza is influenced by prior immunity
      and mixing patterns in the host population, and also by the proportion of
      infections that are asymptomatic. This complexity makes it difficult to directly
      estimate R(0) from the attack rate, contributing to uncertainty in
      epidemiological models to guide pandemic planning. We have modelled multiple wave
      outbreaks of influenza from different populations to allow for changing immunity
      and asymptomatic infection and to make inferences about R(0). DATA AND METHODS:
      On the island of Tristan da Cunha (TdC), 96% of residents reported illness during
      an H3N2 outbreak in 1971, compared with only 25% of RAF personnel in military
      camps during the 1918 H1N1 pandemic. Monte Carlo Markov Chain (MCMC) methods were
      used to estimate model parameter distributions. FINDINGS: We estimated that most
      islanders on TdC were non-immune (susceptible) before the first wave, and that
      almost all exposures of susceptible persons caused symptoms. The median R(0) of
      6.4 (95% credibility interval 3.7-10.7) implied that most islanders were exposed
      twice, although only a minority became ill in the second wave because of
      temporary protection following the first wave. In contrast, only 51% of RAF
      personnel were susceptible before the first wave, and only 38% of exposed
      susceptibles reported symptoms. R(0) in this population was also lower [2.9 (2.3
      4.3)], suggesting reduced viral transmission in a partially immune population.
      INTERPRETATION: Our model implies that the RAF population was partially protected
      before the summer pandemic wave of 1918, arguably because of prior exposure to
      interpandemic influenza. Without such protection, each symptomatic case of
      influenza would transmit to between 2 and 10 new cases, with incidence initially
      doubling every 1-2 days. Containment of a novel virus could be more difficult
      than hitherto supposed.

PMID- 18043734
TI  - An obligatory role of mind bomb-1 in notch signaling of mammalian development.
AB  - BACKGROUND: The Notch signaling pathway is an evolutionarily conserved
      intercellular signaling module essential for cell fate specification that
      requires endocytosis of Notch ligands. Structurally distinct E3 ubiquitin
      ligases, Neuralized (Neur) and Mind bomb (Mib), cooperatively regulate the
      endocytosis of Notch ligands in Drosophila. However, the respective roles of the
      mammalian E3 ubiquitin ligases, Neur1, Neur2, Mib1, and Mib2, in mammalian
      development are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Through
      extensive use of mammalian genetics, here we show that Neur1 and Neur2 double
      mutants and Mib2(-/-) mice were viable and grossly normal. In contrast,
      conditional inactivation of Mib1 in various tissues revealed the representative
      Notch phenotypes: defects of arterial specification as deltalike4 mutants,
      abnormal cerebellum and skin development as jagged1 conditional mutants, and
      syndactylism as jagged2 mutants. CONCLUSIONS/SIGNIFICANCE: Our data provide the
      first evidence that Mib1 is essential for Jagged as well as Deltalike ligand
      mediated Notch signaling in mammalian development, while Neur1, Neur2, and Mib2
      are dispensable.

PMID- 18043735
TI  - Transforming growth factor: beta signaling is essential for limb regeneration in
      axolotls.
AB  - Axolotls (urodele amphibians) have the unique ability, among vertebrates, to
      perfectly regenerate many parts of their body including limbs, tail, jaw and
      spinal cord following injury or amputation. The axolotl limb is the most widely
      used structure as an experimental model to study tissue regeneration. The process
      is well characterized, requiring multiple cellular and molecular mechanisms. The
      preparation phase represents the first part of the regeneration process which
      includes wound healing, cellular migration, dedifferentiation and proliferation.
      The redevelopment phase represents the second part when dedifferentiated cells
      stop proliferating and redifferentiate to give rise to all missing structures. In
      the axolotl, when a limb is amputated, the missing or wounded part is regenerated
      perfectly without scar formation between the stump and the regenerated structure.
      Multiple authors have recently highlighted the similarities between the early
      phases of mammalian wound healing and urodele limb regeneration. In mammals, one
      very important family of growth factors implicated in the control of almost all
      aspects of wound healing is the transforming growth factor-beta family (TGF
      beta). In the present study, the full length sequence of the axolotl TGF-beta1
      cDNA was isolated. The spatio-temporal expression pattern of TGF-beta1 in
      regenerating limbs shows that this gene is up-regulated during the preparation
      phase of regeneration. Our results also demonstrate the presence of multiple
      components of the TGF-beta signaling machinery in axolotl cells. By using a
      specific pharmacological inhibitor of TGF-beta type I receptor, SB-431542, we
      show that TGF-beta signaling is required for axolotl limb regeneration. Treatment
      of regenerating limbs with SB-431542 reveals that cellular proliferation during
      limb regeneration as well as the expression of genes directly dependent on TGF
      beta signaling are down-regulated. These data directly implicate TGF-beta
      signaling in the initiation and control of the regeneration process in axolotls.

PMID- 18043736
TI  - On hemangioblasts in chicken.
AB  - Hemangioblasts are bi-potential precursors for blood and endothelial cells (BCs
      and ECs). Existence of the hemangioblast in vivo by its strict definition, i.e. a
      clonal precursor giving rise to these two cell types after division, is still
      debated. Using a combination of mitotic figure analysis, cell labeling and long
      term cell tracing, we show that, in chicken, cell division does not play a major
      role during the entire ventral mesoderm differentiation process after
      gastrulation. One eighth of cells do undergo at least one round of division, but
      mainly give rise to daughter cells contributing to the same lineage.
      Approximately 7% of the dividing cells that contribute to either the BC or EC
      lineage meet the criteria of true hemangioblasts, with one daughter cell becoming
      a BC and the other an EC. Our data suggest that hemangioblast-type generation of
      BC/EC occurs, but is not used as a major mechanism during early chicken
      development. It remains unclear, however, whether hemangioblast-like progenitor
      cells play a more prominent role in later development.

PMID- 18043738
TI  - Beyond the gene.
AB  - This paper is a response to the increasing difficulty biologists find in agreeing
      upon a definition of the gene, and indeed, the increasing disarray in which that
      concept finds itself. After briefly reviewing these problems, we propose an
      alternative to both the concept and the word gene-an alternative that, like the
      gene, is intended to capture the essence of inheritance, but which is both richer
      and more expressive. It is also clearer in its separation of what the organism
      statically is (what it tangibly inherits) and what it dynamically does (its
      functionality and behavior). Our proposal of a genetic functor, or genitor, is a
      sweeping extension of the classical genotype/phenotype paradigm, yet it appears
      to be faithful to the findings of contemporary biology, encompassing many of the
      recently emerging-and surprisingly complex-links between structure and
      functionality.

PMID- 18043737
TI  - A novel multi-antigen virally vectored vaccine against Mycobacterium avium
      subspecies paratuberculosis.
AB  - BACKGROUND: Mycobacterium avium subspecies paratuberculosis causes systemic
      infection and chronic intestinal inflammation in many species including primates.
      Humans are exposed through milk and from sources of environmental contamination.
      Hitherto, the only vaccines available against Mycobacterium avium subspecies
      paratuberculosis have been limited to veterinary use and comprised attenuated or
      killed organisms. METHODS: We developed a vaccine comprising a fusion construct
      designated HAV, containing components of two secreted and two cell surface
      Mycobacterium avium subspecies paratuberculosis proteins. HAV was transformed
      into DNA, human Adenovirus 5 (Ad5) and Modified Vaccinia Ankara (MVA) delivery
      vectors. Full length expression of the predicted 95 kDa fusion protein was
      confirmed. PRINCIPAL FINDINGS: Vaccination of naive and Mycobacterium avium
      subspecies paratuberculosis infected C57BL/6 mice using DNA-prime/MVA-boost or
      Ad5-prime/MVA-boost protocols was highly immunogenic resulting in significant IFN
      gamma ELISPOT responses by splenocytes against recombinant vaccine antigens and a
      range of HAV specific peptides. This included strong recognition of a T-cell
      epitope GFAEINPIA located near the C-terminus of the fusion protein. Antibody
      responses to recombinant vaccine antigens and HAV specific peptides but not
      GFAEINPIA, also occurred. No immune recognition of vaccine antigens occurred in
      any sham vaccinated Mycobacterium avium subspecies paratuberculosis infected
      mice. Vaccination using either protocol significantly attenuated pre-existing
      Mycobacterium avium subspecies paratuberculosis infection measured by qPCR in
      spleen and liver and the Ad5-prime/MVA-boost protocol also conferred some
      protection against subsequent challenge. No adverse effects of vaccination
      occurred in any of the mice. CONCLUSIONS/SIGNIFICANCE: A range of modern
      veterinary and clinical vaccines for the treatment and prevention of disease
      caused by Mycobacterium avium subspecies paratuberculosis are needed. The present
      vaccine proved to be highly immunogenic without adverse effect in mice and both
      attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection
      and conferred protection against subsequent challenge. Further studies of the
      present vaccine in naturally infected animals and humans are indicated.

PMID- 18043739
TI  - Correlation index-based responsible-enzyme gene screening (CIRES), a novel DNA
      microarray-based method for enzyme gene involved in glycan biosynthesis.
AB  - BACKGROUND: Glycan biosynthesis occurs though a multi-step process that requires
      a variety of enzymes ranging from glycosyltransferases to those involved in
      cytosolic sugar metabolism. In many cases, glycan biosynthesis follows a glycan
      specific, linear pathway. As glycosyltransferases are generally regulated at the
      level of transcription, assessing the overall transcriptional profile for glycan
      biosynthesis genes seems warranted. However, a systematic approach for assessing
      the correlation between glycan expression and glycan-related gene expression has
      not been reported previously. METHODOLOGY: To facilitate genetic analysis of
      glycan biosynthesis, we sought to correlate the expression of genes involved in
      cell-surface glycan formation with the expression of the glycans, as detected by
      glycan-recognizing probes. We performed cross-sample comparisons of gene
      expression profiles using a newly developed, glycan-focused cDNA microarray. Cell
      surface glycan expression profiles were obtained using flow cytometry of cells
      stained with plant lectins. Pearson's correlation coefficients were calculated
      for these profiles and were used to identify enzyme genes correlated with glycan
      biosynthesis. CONCLUSIONS: This method, designated correlation index-based
      responsible-enzyme gene screening (CIRES), successfully identified genes already
      known to be involved in the biosynthesis of certain glycans. Our evaluation of
      CIRES indicates that it is useful for identifying genes involved in the
      biosynthesis of glycan chains that can be probed with lectins using flow
      cytometry.

PMID- 18043740
TI  - Acute sleep deprivation and circadian misalignment associated with transition
      onto the first night of work impairs visual selective attention.
AB  - BACKGROUND: Overnight operations pose a challenge because our circadian biology
      promotes sleepiness and dissipates wakefulness at night. Since the circadian
      effect on cognitive functions magnifies with increasing sleep pressure, cognitive
      deficits associated with night work are likely to be most acute with extended
      wakefulness, such as during the transition from a day shift to night shift.
      METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis we measured selective
      attention (with visual search), vigilance (with Psychomotor Vigilance Task [PVT])
      and alertness (with a visual analog scale) in a shift work simulation protocol,
      which included four day shifts followed by three night shifts. There was a
      nocturnal decline in cognitive processes, some of which were most pronounced on
      the first night shift. The nighttime decrease in visual search sensitivity was
      most pronounced on the first night compared with subsequent nights (p = .04), and
      this was accompanied by a trend towards selective attention becoming 'fast and
      sloppy'. The nighttime increase in attentional lapses on the PVT was
      significantly greater on the first night compared to subsequent nights (p<.05)
      indicating an impaired ability to sustain focus. The nighttime decrease in
      subjective alertness was also greatest on the first night compared with
      subsequent nights (p<.05). CONCLUSIONS/SIGNIFICANCE: These nocturnal deficits in
      attention and alertness offer some insight into why occupational errors,
      accidents, and injuries are pronounced during night work compared to day work.
      Examination of the nighttime vulnerabilities underlying the deployment of
      attention can be informative for the design of optimal work schedules and the
      implementation of effective countermeasures for performance deficits during night
      work.

PMID- 18043741
TI  - Nogo Receptor 1 (RTN4R) as a candidate gene for schizophrenia: analysis using
      human and mouse genetic approaches.
AB  - BACKGROUND: NOGO Receptor 1 (RTN4R) regulates axonal growth, as well as axon
      regeneration after injury. The gene maps to the 22q11.2 schizophrenia
      susceptibility locus and is thus a strong functional and positional candidate
      gene. METHODOLOGY/PRINCIPAL FINDINGS: We evaluate evidence for genetic
      association between common RTN4R polymorphisms and schizophrenia in a large
      family sample of Afrikaner origin and screen the exonic sequence of RTN4R for
      rare variants in an independent sample from the U.S. We also employ animal model
      studies to assay a panel of schizophrenia-related behavioral tasks in an Rtn4r
      deficient mouse model. We found weak sex-specific evidence for association
      between common RTN4R polymorphisms and schizophrenia in the Afrikaner patients.
      In the U.S. sample, we identified two novel non-conservative RTN4R coding
      variants in two patients with schizophrenia that were absent in 600 control
      chromosomes. In our complementary mouse model studies, we identified a
      haploinsufficient effect of Rtn4r on locomotor activity, but normal performance
      in schizophrenia-related behavioral tasks. We also provide evidence that Rtn4r
      deficiency can modulate the long-term behavioral effects of transient postnatal N
      methyl-D-aspartate (NMDA) receptor hypofunction. CONCLUSIONS: Our results do not
      support a major role of RTN4R in susceptibility to schizophrenia or the cognitive
      and behavioral deficits observed in individuals with 22q11 microdeletions.
      However, they suggest that RTN4R may modulate the genetic risk or clinical
      expression of schizophrenia in a subset of patients and identify additional
      studies that will be necessary to clarify the role of RTN4R in psychiatric
      phenotypes. In addition, our results raise interesting issues about evaluating
      the significance of rare genetic variants in disease and their role in causation.

PMID- 18043742
TI  - Gene organization in rice revealed by full-length cDNA mapping and gene
      expression analysis through microarray.
AB  - Rice (Oryza sativa L.) is a model organism for the functional genomics of
      monocotyledonous plants since the genome size is considerably smaller than those
      of other monocotyledonous plants. Although highly accurate genome sequences of
      indica and japonica rice are available, additional resources such as full-length
      complementary DNA (FL-cDNA) sequences are also indispensable for comprehensive
      analyses of gene structure and function. We cross-referenced 28.5K individual
      loci in the rice genome defined by mapping of 578K FL-cDNA clones with the 56K
      loci predicted in the TIGR genome assembly. Based on the annotation status and
      the presence of corresponding cDNA clones, genes were classified into 23K
      annotated expressed (AE) genes, 33K annotated non-expressed (ANE) genes, and 5.5K
      non-annotated expressed (NAE) genes. We developed a 60mer oligo-array for
      analysis of gene expression from each locus. Analysis of gene structures and
      expression levels revealed that the general features of gene structure and
      expression of NAE and ANE genes were considerably different from those of AE
      genes. The results also suggested that the cloning efficiency of rice FL-cDNA is
      associated with the transcription activity of the corresponding genetic locus,
      although other factors may also have an effect. Comparison of the coverage of FL
      cDNA among gene families suggested that FL-cDNA from genes encoding rice- or
      eukaryote-specific domains, and those involved in regulatory functions were
      difficult to produce in bacterial cells. Collectively, these results indicate
      that rice genes can be divided into distinct groups based on transcription
      activity and gene structure, and that the coverage bias of FL-cDNA clones exists
      due to the incompatibility of certain eukaryotic genes in bacteria.

PMID- 18043743
TI  - Lambs with scrapie susceptible genotypes have higher postnatal survival.
AB  - BACKGROUND: Prion protein (PrP) alleles associated with scrapie susceptibility
      persist in many sheep populations even with high frequencies despite centuries of
      selection against them. This suggests that scrapie susceptibility alleles have a
      pleiotropic effect or are associated with fitness or other traits that have been
      subject to selection. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped all lambs in
      two scrapie-free Scottish Blackface sheep flocks for polymorphisms at codons 136,
      154 and 171 of the PrP gene. We tested potential associations of the PrP genotype
      with lamb viability at birth and postnatal survival using a complementary log-log
      link function and a Weibull proportional hazard model, respectively. Here we show
      there is an association between PrP genotype, as defined by polymorphisms at
      codons 154 ad 171, and postnatal lamb survival in the absence of scrapie. Sheep
      carrying the wild-type ARQ allele have higher postnatal survival rates than sheep
      carrying the more scrapie-resistant alleles (ARR or AHQ). CONCLUSION: The PrP
      genotypes associated with higher susceptibility to scrapie are associated with
      improved postnatal survival in the absence of the disease. This association helps
      to explain the existence, and in many instances the high frequency, of the ARQ
      allele in sheep populations.

PMID- 18043744
TI  - Tumor spectrum, tumor latency and tumor incidence of the Pten-deficient mice.
AB  - BACKGROUND: Pten functionally acts as a tumor suppressor gene. Lately, tissue
      specific ablation of Pten gene in mice has elucidated the role of Pten in
      different tumor progression models. However, a temporally controlled Pten loss in
      all adult tissues to examine susceptibility of various tissues to Pten-deficient
      tumorigenesis has not been addressed yet. Our goal was to explore the genesis of
      Pten-deficient malignancies in multiple tissue lineages of the adult mouse.
      METHODS AND FINDINGS: We utilized an inducible Cre/loxP system to delete Pten
      exon 5 in the systemic organs of ROSA26 (R26)-CreER(T);Pten(fx/fx) mice. On
      reaching 45 weeks 4OHT-induced Pten loss, we found that the R26
      CreER(T);Pten(fx/fx) mice developed a variety of malignancies. Overall tumor mean
      latency was 17 weeks in the Pten-deficient mice. Interestingly, mutant females
      developed malignancies more quickly at 10 approximately 11 weeks compared with a
      tumor latency of 21 weeks for mutant males. Lymphoma incidence (76.9% in females;
      40.0% in males) was higher than the other malignancies found in the mutant mice.
      Mutant males developed prostate (20.0%), intestinal cancer (35.0%) and squamous
      cell carcinoma (10.0%), whereas the mutant females developed squamous cell
      carcinoma (15.4%) and endometrial cancer (46.1%) in addition to lymphomas.
      Furthermore, we tested the pharmacological inhibition of the PTEN downstream
      effectors using LY294002 on Pten-deficient prostate hyperplasia. Our data
      revealed that, indeed, the prostate hyperplasia resulting from the induced Pten
      loss was significantly suppressed by LY294002 (p = 0.007). CONCLUSIONS: Through
      monitoring a variety of Pten-deficient tumor formation, our results revealed that
      the lymphoid lineages and the epithelium of the prostate, endometrium, intestine
      and epidermis are highly susceptible to tumorigenesis after the Pten gene is
      excised. Therefore, this R26-CreER(T); Pten(fx/fx) mouse model may provide an
      entry point for understanding the role of Pten in the tumorigenesis of different
      organs and extend the search for potential therapeutic approaches to prevent Pten
      deficient malignancies.

PMID- 18043745
TI  - High CO2 levels impair alveolar epithelial function independently of pH.
AB  - BACKGROUND: In patients with acute respiratory failure, gas exchange is impaired
      due to the accumulation of fluid in the lung airspaces. This life-threatening
      syndrome is treated with mechanical ventilation, which is adjusted to maintain
      gas exchange, but can be associated with the accumulation of carbon dioxide in
      the lung. Carbon dioxide (CO2) is a by-product of cellular energy utilization and
      its elimination is affected via alveolar epithelial cells. Signaling pathways
      sensitive to changes in CO2 levels were described in plants and neuronal
      mammalian cells. However, it has not been fully elucidated whether non-neuronal
      cells sense and respond to CO2. The Na,K-ATPase consumes approximately 40% of the
      cellular metabolism to maintain cell homeostasis. Our study examines the effects
      of increased pCO2 on the epithelial Na,K-ATPase a major contributor to alveolar
      fluid reabsorption which is a marker of alveolar epithelial function. PRINCIPAL
      FINDINGS: We found that short-term increases in pCO2 impaired alveolar fluid
      reabsorption in rats. Also, we provide evidence that non-excitable, alveolar
      epithelial cells sense and respond to high levels of CO2, independently of
      extracellular and intracellular pH, by inhibiting Na,K-ATPase function, via
      activation of PKCzeta which phosphorylates the Na,K-ATPase, causing it to
      endocytose from the plasma membrane into intracellular pools. CONCLUSIONS: Our
      data suggest that alveolar epithelial cells, through which CO2 is eliminated in
      mammals, are highly sensitive to hypercapnia. Elevated CO2 levels impair alveolar
      epithelial function, independently of pH, which is relevant in patients with lung
      diseases and altered alveolar gas exchange.

PMID- 18043746
TI  - The gene transformer of anastrepha fruit flies (Diptera, tephritidae) and its
      evolution in insects.
AB  - In the tephritids Ceratitis capitata and Bactrocera oleae, the gene transformer
      acts as the memory device for sex determination, via an auto-regulatory function;
      and functional Tra protein is produced only in females. This paper investigates
      the evolution of the gene tra, which was characterised in twelve tephritid
      species belonging to the less extensively analysed genus Anastrepha. Our study
      provided the following major conclusions. Firstly, the memory device mechanism
      used by this gene in sex determination in tephritids likely existed in the common
      ancestor of the Ceratitis, Bactrocera and Anastrepha phylogenetic lineages. This
      mechanism would represent the ancestral state with respect to the extant cascade
      seen in the more evolved Drosophila lineage. Secondly, Transformer2-specific
      binding intronic splicing silencer sites were found in the splicing regulatory
      region of transformer but not in doublesex pre-mRNAs in these tephritids. Thus,
      these sites probably provide the discriminating feature for the putative dual
      splicing activity of the Tra-Tra2 complex in tephritids. It acts as a splicing
      activator in dsx pre-mRNA splicing (its binding to the female-specific exon
      promotes the inclusion of this exon into the mature mRNA), and as a splicing
      inhibitor in tra pre-mRNA splicing (its binding to the male-specific exons
      prevents the inclusion of these exons into the mature mRNA). Further, a highly
      conserved region was found in the specific amino-terminal region of the tephritid
      Tra protein that might be involved in Tra auto-regulatory function and hence in
      its repressive splicing behaviour. Finally, the Tra proteins conserved the SR
      dipeptides, which are essential for Tra functionality.

PMID- 18043747
TI  - DAF-2/insulin-like signaling in C. elegans modifies effects of dietary
      restriction and nutrient stress on aging, stress and growth.
AB  - BACKGROUND: Dietary restriction (DR) and reduced insulin/IGF-I-like signaling
      (IIS) are two regimens that promote longevity in a variety of organisms. Genetic
      analysis in C. elegans nematodes has shown that DR and IIS couple to distinct
      cellular signaling pathways. However, it is not known whether these pathways
      ultimately converge on overlapping or distinct targets to extend lifespan.
      PRINCIPAL FINDINGS: We investigated this question by examining additional effects
      of DR in wildtype animals and in daf-2 mutants with either moderate or severe IIS
      deficits. Surprisingly, DR and IIS had opposing effects on these physiological
      processes. First, DR induced a stress-related change in intestinal vesicle
      trafficking, termed the FIRE response, which was suppressed in daf-2 mutants.
      Second, DR did not strongly affect expression of a daf-2- and stress-responsive
      transcriptional reporter. Finally, DR-related growth impairment was suppressed in
      daf-2 mutants. CONCLUSIONS: These findings reveal that an important biological
      function of DAF-2/IIS is to enhance growth and survival under nutrient-limited
      conditions. However, we also discovered that levels of DAF-2 pathway activity
      modified the effects of DR on longevity. Thus, while DR and IIS clearly affect
      lifespan through independent targets, there may also be some prolongevity targets
      that are convergently regulated by these pathways.

PMID- 18043748
TI  - Subcellular distribution of mitochondrial ribosomal RNA in the mouse oocyte and
      zygote.
AB  - Mitochondrial ribosomal RNAs (mtrRNAs) have been reported to translocate extra
      mitochondrially and localize to the germ cell determinant of oocytes and zygotes
      in some metazoa except mammals. To address whether the mtrRNAs also localize in
      the mammals, expression and distribution of mitochondrion-encoded RNAs in the
      mouse oocytes and zygotes was examined by whole-mount in situ hybridization
      (ISH). Both 12S and 16S rRNAs were predominantly distributed in the animal
      hemisphere of the mature oocyte. This distribution pattern was rearranged toward
      the second polar body in zygotes after fertilization. The amount of mtrRNAs
      decreased around first cleavage, remained low during second cleavage and
      increased after third cleavage. Staining intensity of the 12S rRNA was weaker
      than that of the 16S rRNA throughout the examined stages. Similar distribution
      dynamics of the 16S rRNA was observed in strontium-activated haploid parthenotes,
      suggesting the distribution rearrangement does not require a component from
      sperm. The distribution of 16S rRNAs did not coincide with that of mitochondrion
      specific heat shock protein 70, suggesting that the mtrRNA is translocated from
      mitochondria. The ISH-scanning electron microscopy confirms the extra
      mitochondrial mtrRNA in the mouse oocyte. Chloramphenicol (CP) treatment of late
      pronuclear stage zygotes perturbed first cleavage as judged by the greater than
      normal disparity in size of blastomeres of 2-cell conceptuses. Two-third of the
      CP-treated zygotes arrested at either 2-cell or 3-cell stage even after the CP
      was washed out. These findings indicate that the extra-mitochondrial mtrRNAs are
      localized in the mouse oocyte and implicated in correct cytoplasmic segregation
      into blastomeres through cleavages of the zygote.

PMID- 18043749
TI  - Physical analyses of E. coli heteroduplex recombination products in vivo: on the
      prevalence of 5' and 3' patches.
AB  - BACKGROUND: Homologous recombination in Escherichia coli creates patches (non
      crossovers) or splices (half crossovers), each of which may have associated
      heteroduplex DNA. Heteroduplex patches have recombinant DNA in one strand of the
      duplex, with parental flanking markers. Which DNA strand is exchanged in
      heteroduplex patches reflects the molecular mechanism of recombination. Several
      models for the mechanism of E. coli RecBCD-mediated recombinational double-strand
      end (DSE) repair specify that only the 3'-ending strand invades the homologous
      DNA, forming heteroduplex in that strand. There is, however, in vivo evidence
      that patches are found in both strands. METHODOLOGY/PRINCIPLE FINDINGS: This
      paper re-examines heteroduplex-patch-strand polarity using phage lambda and the
      lambdadv plasmid as DNA substrates recombined via the E. coli RecBCD system in
      vivo. These DNAs are mutant for lambda recombination functions, including orf and
      rap, which were functional in previous studies. Heteroduplexes are isolated,
      separated on polyacrylamide gels, and quantified using Southern blots for
      heteroduplex analysis. This method reveals that heteroduplexes are still found in
      either 5' or 3' DNA strands in approximately equal amounts, even in the absence
      of orf and rap. Also observed is an independence of the RuvC Holliday-junction
      endonuclease on patch formation, and a slight but statistically significant
      alteration of patch polarity by recD mutation. CONCLUSIONS/SIGNIFICANCE: These
      results indicate that orf and rap did not contribute to the presence of patches,
      and imply that patches occurring in both DNA strands reflects the molecular
      mechanism of recombination in E. coli. Most importantly, the lack of a
      requirement for RuvC implies that endonucleolytic resolution of Holliday
      junctions is not necessary for heteroduplex-patch formation, contrary to
      predictions of all of the major previous models. This implies that patches are
      not an alternative resolution of the same intermediate that produces splices, and
      do not bear on models for splice formation. We consider two mechanisms that use
      DNA replication instead of endonucleolytic resolution for formation of
      heteroduplex patches in either DNA strand: synthesis-dependent-strand annealing
      and a strand-assimilation mechanism.

PMID- 18043750
TI  - Multiple origins of knockdown resistance mutations in the Afrotropical mosquito
      vector Anopheles gambiae.
AB  - How often insecticide resistance mutations arise in natural insect populations is
      a fundamental question for understanding the evolution of resistance and also for
      modeling its spread. Moreover, the development of resistance is regarded as a
      favored model to study the molecular evolution of adaptive traits. In the malaria
      vector Anopheles gambiae two point mutations (L1014F and L1014S) in the voltage
      gated sodium channel gene, that confer knockdown resistance (kdr) to DDT and
      pyrethroid insecticides, have been described. In order to determine whether
      resistance alleles result from single or multiple mutation events, genotyping of
      the kdr locus and partial sequencing of the upstream intron-1 was performed on a
      total of 288 A. gambiae S-form collected from 28 localities in 15 countries.
      Knockdown resistance alleles were found to be widespread in West Africa with co
      occurrence of both 1014S and 1014F in West-Central localities. Differences in
      intron-1 haplotype composition suggest that kdr alleles may have arisen from at
      least four independent mutation events. Neutrality tests provided evidence for a
      selective sweep acting on this genomic region, particularly in West Africa. The
      frequency and distribution of these kdr haplotypes varied geographically, being
      influenced by an interplay between different mutational occurrences, gene flow
      and local selection. This has important practical implications for the management
      and sustainability of malaria vector control programs.

PMID- 18043751
TI  - Admixture mapping provides evidence of association of the VNN1 gene with
      hypertension.
AB  - Migration patterns in modern societies have created the opportunity to use
      population admixture as a strategy to identify susceptibility genes. To implement
      this strategy, we genotyped a highly informative ancestry marker panel of 2270
      single nucleotide polymorphisms in a random population sample of African
      Americans (N = 1743), European Americans (N = 1000) and Mexican Americans (N =
      581). We then examined the evidence for over-transmission of specific loci to
      cases from one of the two ancestral populations. Hypertension cases and controls
      were defined based on standard clinical criteria. Both case-only and case-control
      analyses were performed among African Americans. With the genome-wide markers we
      replicated the findings identified in our previous admixture mapping study on
      chromosomes 6 and 21 [1]. For case-control analysis we then genotyped 51 missense
      SNPs in 36 genes spaced across an 18.3 Mb region. Further analyses demonstrated
      that the missense SNP rs2272996 (or N131S) in the VNN1 gene was significantly
      associated with hypertension in African Americans and the association was
      replicated in Mexican Americans; a non-significant opposite association was
      observed in European Americans. This SNP also accounted for most of the evidence
      observed in the admixture analysis on chromosome 6. Despite these encouraging
      results, susceptibility loci for hypertension have been exceptionally difficult
      to localize and confirmation by independent studies will be necessary to
      establish these findings.

PMID- 18043752
TI  - A conceptual framework for mapping quantitative trait Loci regulating ontogenetic
      allometry.
AB  - Although ontogenetic changes in body shape and its associated allometry has been
      studied for over a century, essentially nothing is known about their underlying
      genetic and developmental mechanisms. One of the reasons for this ignorance is
      the unavailability of a conceptual framework to formulate the experimental design
      for data collection and statistical models for data analyses. We developed a
      framework model for unraveling the genetic machinery for ontogenetic changes of
      allometry. The model incorporates the mathematical aspects of ontogenetic growth
      and allometry into a maximum likelihood framework for quantitative trait locus
      (QTL) mapping. As a quantitative platform, the model allows for the testing of a
      number of biologically meaningful hypotheses to explore the pleiotropic basis of
      the QTL that regulate ontogeny and allometry. Simulation studies and real data
      analysis of a live example in soybean have been performed to investigate the
      statistical behavior of the model and validate its practical utilization. The
      statistical model proposed will help to study the genetic architecture of complex
      phenotypes and, therefore, gain better insights into the mechanistic regulation
      for developmental patterns and processes in organisms.

PMID- 18043753
TI  - An intronic signal for alternative splicing in the human genome.
AB  - An important level at which the expression of programmed cell death (PCD) genes
      is regulated is alternative splicing. Our previous work identified an intronic
      splicing regulatory element in caspase-2 (casp-2) gene. This 100-nucleotide
      intronic element, In100, consists of an upstream region containing a decoy 3'
      splice site and a downstream region containing binding sites for splicing
      repressor PTB. Based on the signal of In100 element in casp-2, we have detected
      the In100-like sequences as a family of sequence elements associated with
      alternative splicing in the human genome by using computational and experimental
      approaches. A survey of human genome reveals the presence of more than four
      thousand In100-like elements in 2757 genes. These In100-like elements tend to
      locate more frequent in intronic regions than exonic regions. EST analyses
      indicate that the presence of In100-like elements correlates with the skipping of
      their immediate upstream exons, with 526 genes showing exon skipping in such a
      manner. In addition, In100-like elements are found in several human caspase genes
      near exons encoding the caspase active domain. RT-PCR experiments show that these
      caspase genes indeed undergo alternative splicing in a pattern predicted to
      affect their functional activity. Together, these results suggest that the In100
      like elements represent a family of intronic signals for alternative splicing in
      the human genome.

PMID- 18043754
TI  - Brain responses to violet, blue, and green monochromatic light exposures in
      humans: prominent role of blue light and the brainstem.
AB  - BACKGROUND: Relatively long duration retinal light exposure elicits nonvisual
      responses in humans, including modulation of alertness and cognition. These
      responses are thought to be mediated in part by melanopsin-expressing retinal
      ganglion cells which are more sensitive to blue light than violet or green light.
      The contribution of the melanopsin system and the brain mechanisms involved in
      the establishment of such responses to light remain to be established.
      METHODOLOGY/PRINCIPAL FINDINGS: We exposed 15 participants to short duration (50
      s) monochromatic violet (430 nm), blue (473 nm), and green (527 nm) light
      exposures of equal photon flux (10(13)ph/cm(2)/s) while they were performing a
      working memory task in fMRI. At light onset, blue light, as compared to green
      light, increased activity in the left hippocampus, left thalamus, and right
      amygdala. During the task, blue light, as compared to violet light, increased
      activity in the left middle frontal gyrus, left thalamus and a bilateral area of
      the brainstem consistent with activation of the locus coeruleus.
      CONCLUSION/SIGNIFICANCE: These results support a prominent contribution of
      melanopsin-expressing retinal ganglion cells to brain responses to light within
      the very first seconds of an exposure. The results also demonstrate the
      implication of the brainstem in mediating these responses in humans and speak for
      a broad involvement of light in the regulation of brain function.

PMID- 18043755
TI  - A tale of four stories: soil ecology, theory, evolution and the publication
      system.
AB  - BACKGROUND: Soil ecology has produced a huge corpus of results on relations
      between soil organisms, ecosystem processes controlled by these organisms and
      links between belowground and aboveground processes. However, some soil
      scientists think that soil ecology is short of modelling and evolutionary
      approaches and has developed too independently from general ecology. We have
      tested quantitatively these hypotheses through a bibliographic study (about 23000
      articles) comparing soil ecology journals, generalist ecology journals,
      evolutionary ecology journals and theoretical ecology journals. FINDINGS: We have
      shown that soil ecology is not well represented in generalist ecology journals
      and that soil ecologists poorly use modelling and evolutionary approaches.
      Moreover, the articles published by a typical soil ecology journal (Soil Biology
      and Biochemistry) are cited by and cite low percentages of articles published in
      generalist ecology journals, evolutionary ecology journals and theoretical
      ecology journals. CONCLUSION: This confirms our hypotheses and suggests that soil
      ecology would benefit from an effort towards modelling and evolutionary
      approaches. This effort should promote the building of a general conceptual
      framework for soil ecology and bridges between soil ecology and general ecology.
      We give some historical reasons for the parsimonious use of modelling and
      evolutionary approaches by soil ecologists. We finally suggest that a publication
      system that classifies journals according to their Impact Factors and their level
      of generality is probably inadequate to integrate "particularity" (empirical
      observations) and "generality" (general theories), which is the goal of all
      natural sciences. Such a system might also be particularly detrimental to the
      development of a science such as ecology that is intrinsically multidisciplinary.

PMID- 18043756
TI  - Mosaic genome architecture of the Anopheles gambiae species complex.
AB  - BACKGROUND: Attempts over the last three decades to reconstruct the phylogenetic
      history of the Anopheles gambiae species complex have been important for
      developing better strategies to control malaria transmission. METHODOLOGY: We
      used fingerprint genotyping data from 414 field-collected female mosquitoes at 42
      microsatellite loci to infer the evolutionary relationships of four species in
      the A. gambiae complex, the two major malaria vectors A. gambiae sensu stricto
      (A. gambiae s.s.) and A. arabiensis, as well as two minor vectors, A. merus and
      A. melas. PRINCIPAL FINDINGS: We identify six taxonomic units, including a clear
      separation of West and East Africa A. gambiae s.s. S molecular forms. We show
      that the phylogenetic relationships vary widely between different genomic
      regions, thus demonstrating the mosaic nature of the genome of these species. The
      two major malaria vectors are closely related and closer to A. merus than to A.
      melas at the genome-wide level, which is also true if only autosomes are
      considered. However, within the Xag inversion region of the X chromosome, the M
      and two S molecular forms are most similar to A. merus. Near the X centromere,
      outside the Xag region, the two S forms are highly dissimilar to the other taxa.
      Furthermore, our data suggest that the centromeric region of chromosome 3 is a
      strong discriminator between the major and minor malaria vectors. CONCLUSIONS:
      Although further studies are needed to elucidate the basis of the phylogenetic
      variation among the different regions of the genome, the preponderance of
      sympatric admixtures among taxa strongly favor introgression of different genomic
      regions between species, rather than lineage sorting of ancestral polymorphism,
      as a possible mechanism.

PMID- 18043757
TI  - Active hippocampal networks undergo spontaneous synaptic modification.
AB  - The brain is self-writable; as the brain voluntarily adapts itself to a changing
      environment, the neural circuitry rearranges its functional connectivity by
      referring to its own activity. How the internal activity modifies synaptic
      weights is largely unknown, however. Here we report that spontaneous activity
      causes complex reorganization of synaptic connectivity without any external (or
      artificial) stimuli. Under physiologically relevant ionic conditions, CA3
      pyramidal cells in hippocampal slices displayed spontaneous spikes with bistable
      slow oscillations of membrane potential, alternating between the so-called UP and
      DOWN states. The generation of slow oscillations did not require fast synaptic
      transmission, but their patterns were coordinated by local circuit activity. In
      the course of generating spontaneous activity, individual neurons acquired
      bidirectional long-lasting synaptic modification. The spontaneous synaptic
      plasticity depended on a rise in intracellular calcium concentrations of
      postsynaptic cells, but not on NMDA receptor activity. The direction and amount
      of the plasticity varied depending on slow oscillation patterns and synapse
      locations, and thus, they were diverse in a network. Once this global synaptic
      refinement occurred, the same neurons now displayed different patterns of
      spontaneous activity, which in turn exhibited different levels of synaptic
      plasticity. Thus, active networks continuously update their internal states
      through ongoing synaptic plasticity. With computational simulations, we suggest
      that with this slow oscillation-induced plasticity, a recurrent network converges
      on a more specific state, compared to that with spike timing-dependent plasticity
      alone.

PMID- 18043758
TI  - Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv
      mice.
AB  - BACKGROUND: The HIV-1 maturation inhibitor, 3-O-(3',3'-dimethylsuccinyl)
      betulinic acid (bevirimat, PA-457) is a promising drug candidate with 10 nM in
      vitro antiviral activity against multiple wild-type (WT) and drug-resistant HIV-1
      isolates. Bevirimat has a novel mechanism of action, specifically inhibiting
      cleavage of spacer peptide 1 (SP1) from the C-terminus of capsid which results in
      defective core condensation. METHODS AND FINDINGS: Oral administration of
      bevirimat to HIV-1-infected SCID-hu Thy/Liv mice reduced viral RNA by >2 log(10)
      and protected immature and mature T cells from virus-mediated depletion. This
      activity was observed at plasma concentrations that are achievable in humans
      after oral dosing, and bevirimat was active up to 3 days after inoculation with
      both WT HIV-1 and an AZT-resistant HIV-1 clinical isolate. Consistent with its
      mechanism of action, bevirimat caused a dose-dependent inhibition of capsid-SP1
      cleavage in HIV-1-infected human thymocytes obtained from these mice. HIV-1 NL4-3
      with an alanine-to-valine substitution at the N-terminus of SP1 (SP1/A1V), which
      is resistant to bevirimat in vitro, was also resistant to bevirimat treatment in
      the mice, and SP1/AIV had replication and thymocyte kinetics similar to that of
      WT NL4-3 with no evidence of fitness impairment in in vivo competition assays.
      Interestingly, protease inhibitor-resistant HIV-1 with impaired capsid-SP1
      cleavage was hypersensitive to bevirimat in vitro with a 50% inhibitory
      concentration 140 times lower than for WT HIV-1. CONCLUSIONS: These results
      support further clinical development of this first-in-class maturation inhibitor
      and confirm the usefulness of the SCID-hu Thy/Liv model for evaluation of in vivo
      antiretroviral efficacy, drug resistance, and viral fitness.

PMID- 18043759
TI  - Transcriptional networks in S. cerevisiae linked to an accumulation of base
      excision repair intermediates.
AB  - Upon exposure to DNA damaging agents, Saccharomyces cerevisiae respond by
      activating a massive transcriptional program that reflects the fact that "DNA
      damaging" agents also damage other cellular macromolecules. To identify the
      transcriptional response that is specific to DNA damage, we have modulated the
      first two enzymes in the base excision repair (BER) pathway generating yeast
      strains with varied levels of the repair intermediates, abasic sites or strand
      breaks. We show that the number of abasic sites is significantly increased when
      the 3-methyladenine DNA glycosylase (Mag): AP endonuclease (Apn1) ratio is
      increased and that spontaneous frame shift mutation is considerably elevated when
      either Mag, or Mag plus Apn1, expression is elevated. Expression profiling
      identified 633 ORFs with differential expression associated with BER modulation.
      Analysis of transcriptional networks associated with the accumulation of DNA
      repair intermediates identifies an enrichment for numerous biological processes.
      Moreover, most of the BER-activated transcriptional response was independent of
      the classical yeast environmental stress response (ESR). This study highlights
      that DNA damage in the form of abasic sites or strand breaks resulting from BER
      modulation is a trigger for substantial genome-wide change and that this response
      is largely ESR-independent. Taken together, these results suggest that a branch
      point exists in the current model for DNA damage-signaled transcription in S.
      cerevisiae.

PMID- 18043760
TI  - The effect of predictability on subjective duration.
AB  - Events can sometimes appear longer or shorter in duration than other events of
      equal length. For example, in a repeated presentation of auditory or visual
      stimuli, an unexpected object of equivalent duration appears to last longer.
      Illusions of duration distortion beg an important question of time
      representation: when durations dilate or contract, does time in general slow down
      or speed up during that moment? In other words, what entailments do duration
      distortions have with respect to other timing judgments? We here show that when a
      sound or visual flicker is presented in conjunction with an unexpected visual
      stimulus, neither the pitch of the sound nor the frequency of the flicker is
      affected by the apparent duration dilation. This demonstrates that subjective
      time in general is not slowed; instead, duration judgments can be manipulated
      with no concurrent impact on other temporal judgments. Like spatial vision, time
      perception appears to be underpinned by a collaboration of separate neural
      mechanisms that usually work in concert but are separable. We further show that
      the duration dilation of an unexpected stimulus is not enhanced by increasing its
      saliency, suggesting that the effect is more closely related to prediction
      violation than enhanced attention. Finally, duration distortions induced by
      violations of progressive number sequences implicate the involvement of high
      level predictability, suggesting the involvement of areas higher than primary
      visual cortex. We suggest that duration distortions can be understood in terms of
      repetition suppression, in which neural responses to repeated stimuli are
      diminished.

PMID- 18043761
TI  - Identification of novel Drosophila melanogaster microRNAs.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs with important regulatory roles in
      post-transcriptional regulation of metazoan development, homeostasis and disease.
      The full set of miRNAs is not known for any species and it is believed that many
      await discovery. The recent assembly of 15 insect genomes has provided the
      opportunity to identify novel miRNAs in the fruit fly, Drosophila melanogaster.
      We have performed a computational screen for novel microRNAs in Drosophila
      melanogaster by searching for phylogenetically conserved putative pre-miRNA
      structures. The ability of predicted novel miRNA precursors to be processed to
      produce miRNAs was experimentally verified in S2 cells and in several cases their
      endogenous expression at was validated by Northern blots. After experimental
      validation, the predictions were cross-checked with reference to a newly released
      set of small RNA sequences. Combining both datasets allowed us to identify 53
      novel miRNA loci in the fruit fly genome 22 of which we had predicted
      computationally. This significantly expands the set of known miRNAs in Drosophila
      melanogaster. Most novel miRNAs contain unique seed sequences not found in other
      Drosophila miRNAs and are therefore expected to regulate novel sets of target
      genes. This data provides the basis for future genetic analysis of miRNA function
      and will aid the discovery of orthologous sequences in other species.

PMID- 18043762
TI  - How to increase serotonin in the human brain without drugs.

PMID- 18043763
TI  - Dopaminergic regulation of limbic-striatal interplay.
AB  - Neurochemical, electrophysiological and behavioural evidence indicates that
      certain forms of goal-directed behaviours are mediated by complex and reciprocal
      interactions between limbic and dopamine (DA) inputs in the nucleus accumbens
      (NAc). Mesoaccumbens DA transmission appears to be compartmentalized; synaptic DA
      transmission is mediated by phasic burst firing of DA neurons, whereas
      extrasynaptic tonic DA levels are regulated by DA neuron population activity and
      limbic glutamatergic inputs to the NAc. DA release facilitated by limbic inputs
      and acting on D1 receptors can either potentiate or suppress neural activity
      driven by separate limbic inputs converging on the same postsynaptic NAc neurons.
      In turn, D1 receptors in the NAc mediate accuracy of search behaviour regulated
      by hippocampal-ventral striatal circuitries; D2 receptors appear to mediate
      motivational aspects of task performance. These findings suggest that
      dopaminergic modulation of limbic afferents to the NAc may be a cellular
      mechanism for input selection that governs the smooth coordination of behaviour
      by permitting information processed by one limbic region to temporarily exert
      control over the type and intensity of adaptive behavioural responses.

PMID- 18043764
TI  - Association of alpha4beta2 nicotinic receptor and heavy smoking in schizophrenia.
AB  - INTRODUCTION: Previously we suggested that the CHRNA7 polymorphism in nicotinic
      receptor genes, in particular the D15S1360 in CHRNA7, is associated with smoking
      in schizophrenia. Schizophrenia patients are usually heavy smokers. In this study
      we hypothesized that high-affinity nicotinic receptors are associated with
      smoking in such patients. OBJECTIVE: To investigate the role of alpha4 (Ch 20)
      and beta2 (Ch 1) genes in conferring a risk for smoking and for smoking a large
      number of cigarettes daily in subjects with schizophrenia. METHODS: Our study
      sample consisted of 241 white European schizophrenia patients (157 smokers and 84
      nonsmokers) from the Toronto area. Current smoking status was assessed by the
      medical history. We investigated 4 markers located in the CHRNA4 gene and 3
      markers located in the CHRNB2 gene. RESULTS: There was no difference in age or
      ethnicity between the 2 groups and the population was not stratified
      (lambda=0.4527). We found a significant association between the CHRNA4 rs3746372
      allele 1 and a large number of cigarettes smoked daily (p=0.0203). The intragenic
      interaction between rs3787116 and rs3746372 (p = 0.0050) in CHRNA4 showed a
      significant interaction for the number of cigarettes smoked. CONCLUSION: Although
      our findings suggest an association between rs3746372 allele 1 and heavy smoking,
      further study is warranted to investigate the relation between smoking and high
      affinity nicotinic receptor genes in schizophrenia.

PMID- 18043765
TI  - Corpus callosum abnormalities in women with borderline personality disorder and
      comorbid attention-deficit hyperactivity disorder.
AB  - OBJECTIVE: Decreased brain volumes in prefrontal, limbic and parietal areas have
      been found in women with borderline personality disorder (BPD). Recent models
      suggest impaired structural and functional connectivity in this condition. To
      investigate this, we studied the thickness of the corpus callosum, the largest
      connecting fibre bundle in the human brain. METHODS: We acquired magnetic
      resonance imaging scans from 20 healthy women and 20 women with BPD and comorbid
      attention-deficit hyperactivity disorder. A novel computational mesh-based method
      was applied to measure callosal thickness at high spatial resolution. RESULTS:
      Women with BPD had a thinner isthmus of the corpus callosum, compared with
      healthy women. In the patient group, a history of childhood sexual abuse was
      associated with a thinner posterior body of the corpus callosum. CONCLUSION:
      Interhemispheric structural connectivity involving parietal and temporal areas
      may be impaired in women with BPD and comorbid attention-deficit hyperactivity
      disorder.

PMID- 18043766
TI  - Amygdala reactivity to masked negative faces is associated with automatic
      judgmental bias in major depression: a 3 T fMRI study.
AB  - OBJECTIVE: In a previous study, we demonstrated that amygdala reactivity to
      masked negative facial emotions predicts negative judgmental bias in healthy
      subjects. In the present study, we extended the paradigm to a sample of 35
      inpatients suffering from depression to investigate the effect of amygdala
      reactivity on automatic negative judgmental bias and clinical characteristics in
      depression. METHODS: Amygdala activity was recorded in response to masked
      displays of angry, sad and happy facial expressions by means of functional
      magnetic resonance imaging at 3 T. In a subsequent experiment, the patients
      performed an affective priming task that characterizes automatic emotion
      processing by investigating the biasing effect of subliminally presented
      emotional faces on evaluative ratings to subsequently presented neutral stimuli.
      RESULTS: Significant associations between (right) amygdala reactivity and
      automatic negative judgmental bias were replicated in our patient sample (r=
      0.59, p<0.001). Further, negatively biased evaluative processing was associated
      with severity and longer course of illness (r=-0.57, p=0.001). CONCLUSION:
      Amygdala hyperactivity is a neural substrate of negatively biased automatic
      emotion processing that could be a determinant for a more severe disease course.

PMID- 18043767
TI  - In vivo measurements of brain trapping of C-labelled alpha-methyl-L-tryptophan
      during acute changes in mood states.
AB  - BACKGROUND: Little is known about the specific contribution of serotonin (5-HT)
      to the neurobiology of emotion and mood in healthy people. In an exploratory
      study, we sought to investigate the effect of rapid and sustained changes of
      emotional state on the trapping of 11C-labelled alpha-methyl-L-tryptophan (11C
      alphaMtrp) used as a proxy of 5-HT synthesis, using positron emission tomography
      (PET). METHOD: In a within-subject repeated-measure design, participants recalled
      autobiographical memories to self-induce sadness, happiness and a neutral
      emotional state during scanning to measure brain trapping of 11C-alphaMtrp. Three
      separate scan acquisitions, counterbalanced for order across subjects, took place
      at the McConnell Brain Imaging Center, Montreal. RESULTS: Whole brain analysis
      revealed positive and negative correlations between experienced levels of
      emotions and 11C-alphaMtrp trapping in the right anterior cingulate cortex.
      CONCLUSION: These findings point to a mechanism whereby state-related changes in
      a proxy of 5-HT synthesis underscore aspects of the self-regulation of normal
      mood.

PMID- 18043770
TI  - Sitting on the edge: when to treat symptoms of inattention without the full DSM
      IV criteria of ADHD.

PMID- 18043768
TI  - Malondialdehyde levels in adult attention-deficit hyperactivity disorder.
AB  - OBJECTIVE: To evaluate the biochemical basis of adult attention-deficit
      hyperactivity disorder (A-ADHD), we compared lipid peroxidation status in the
      plasma of A-ADHD patients, and that of control subjects without A-ADHD by
      quantifying the levels of malondialdehyde (MDA), an end product of fatty acid
      oxidation. We aimed to examine the association between MDA and A-ADHD. METHOD:
      The study comprised 20 A-ADHD patients from Gaziantep University Sahinbey
      Research Hospital Psychiatry Clinic, diagnosed by 2 psychiatrists (H.A.S. and
      S.S.) according to the Turkish version of the adult ADD/ADHD DSM-IV-Based
      Diagnostic Screening and Rating Scale, and 21 healthy volunteers. Malondialdehyde
      levels were measured in plasma samples of both study groups. RESULTS: The mean
      (standard deviation [SD]) MDA levels in patients (2.44 [0.84] nmol/mL) were
      significantly higher than those of control subjects (0.36 [0.20] nmol/mL)
      (t=11.013, df=39, p<0.01). MDA levels were correlated with overall number of
      criteria met (n=20, p=0.01, Ro=0.56) and total hyperactivity/impulsivity score
      (n=20, p=0.02, Ro=0.51). CONCLUSION: The fact that MDA levels were increased in A
      ADHD could be an indication of increased oxidative stress in this disease. We
      suggest that such changes may have a pathological role in A-ADHD. This is the
      first study evaluating the MDA levels in A-ADHD, and our findings may provide a
      scientific guide for the further clinical enzymologic and biochemical studies on
      this disorder.

PMID- 18043771
TI  - Reducing the impact of stroke.

PMID- 18043772
TI  - Management of stroke in general practice.
AB  - Between April 2002 and March 2007, there were 1171 consultations where stroke was
      managed, occurring at over 2 per 1000 encounters. This suggests that general
      practitioners manage stroke on about 237 000 occasions nationally each year.

PMID- 18043773
TI  - Time is brain--acute stroke management.
AB  - BACKGROUND: In recent years, four specific strategies have emerged which have
      proven clinical benefit in treating acute stroke. These are the administration of
      tissue plasminogen activator (tPA), aspirin, management in a stroke care unit
      (SCU) and the use of hemicraniectomy in patients with severe cerebral oedema.
      OBJECTIVE: This article discusses current management strategies and evidence with
      emphasis on the role of the general practitioner in initial diagnosis and
      hospitalisation. DISCUSSION: Although tPA has been shown to be remarkably
      clinically effective, less than 5% of eligible stroke patients receive this
      therapy. The main obstacle is its very narrow therapeutic time window of 3 hours.
      This necessitates the immediate recognition of stroke and rapid transfer to
      hospital. Computerised tomography is mandatory to rule out cerebral haemorrhage.
      Starting aspirin within 48 hours of stroke onset in patients with ischaemic
      stroke results in a significant reduction in mortality and morbidity. Management
      in a SCU is the most useful intervention with significant reductions in mortality
      and morbidity for all stroke subtypes. The management of stroke is changing, and
      the role of the GP is crucial in facilitating the rapid transfer of patients to a
      SCU together with subsequent risk factor control and community support.

PMID- 18043774
TI  - Stroke in children.
AB  - BACKGROUND: Stroke is a major cause of disability and death in children. It can
      have devastating consequences for families and enormous costs to society.
      Although considered rare, stroke is more common in children than brain tumours.
      Ten percent of children suffering stroke will die as a result, and at least 50%
      of survivors are left with significant neurological disabilities, learning
      difficulties or seizures. OBJECTIVE: This article discusses risk factors,
      investigation, management and outcomes of ischaemic and haemorrhagic stroke in
      neonates and children. DISCUSSION: Arteriopathies and cardiac disease are the
      commonest risk factors for childhood arterial ischaemic stroke (AIS). The cause
      of perinatal AIS is poorly understood, despite affecting 1 in 4000 newborns.
      Sinovenous thrombosis is commonly associated with head and neck infections, and
      haemorrhagic stroke with arterio-venous malformations. Magnetic resonance imaging
      is the diagnostic investigation of choice. Treatment recommendations are
      extrapolated from adults due to a lack of prospective interventional studies.

PMID- 18043775
TI  - Acute stroke patients--early hospital management.
AB  - BACKGROUND: Patients with acute stroke have improved outcomes when managed in a
      stroke unit providing multidisciplinary care, including early rehabilitation.
      OBJECTIVE: This article provides an overview of early hospital management and
      rehabilitation for stroke patients. DISCUSSION: Stroke and transient ischaemic
      attack are medical emergencies. Both have time dependent therapy and the risk of
      a recurrent event is highest in the hours to days after the initial event.
      Important aspects of early hospital management include: rapid confirmation of the
      stroke diagnosis with computerised tomography or magnetic resonance imaging,
      urgent investigations for the cause of stroke, acute therapy, early institution
      of specific secondary prevention strategies, comprehensive risk factor management
      including antihypertensive therapy, early rehabilitation, and discharge planning.
      Investigation and management needs to be tailored to the individual patient,
      taking into account presentation and comorbidities.

PMID- 18043776
TI  - Community care after stroke.
AB  - BACKGROUND: The key to life after stroke is to harness the best secondary
      preventive strategies and maximise functional outcome. OBJECTIVE: This article
      discusses key assessment and secondary prevention strategies for the initial, and
      subsequent, general practitioner visits by patients poststroke. DISCUSSION: Key
      to successful community medical treatment is an accurate diagnosis of the index
      event, as secondary preventive strategies differ depending on the pathology of
      stroke. There are hundreds of evidence based rehabilitation strategies to help
      improve aspects of stroke disability, and there is now good evidence to be more
      optimistic about brain recovery. Rehabilitation strategies can be effective after
      hospital discharge, and can help improve function should this deteriorate long
      after the initial stroke. Sadly, some people are left very disabled after stroke.
      When there is no prospect of further functional recovery, priorities should
      switch to overseeing complex care plans and providing appropriate comfort
      measures.

PMID- 18043777
TI  - Stroke resources for GPs.

PMID- 18043778
TI  - Complementary therapies for cerebrovascular disease.
AB  - Cardiovascular disease (CVD) is still the major cause of death in Australia,
      although it is slowly being overtaken by cancer with regard to mortality, and
      depression with regard to total burden of disease. There are many well known
      medical and surgical options for managing CVD but, as with other chronic
      conditions, an increasing number of people are exploring complementary therapies
      as an adjunct to medical treatment. This article explores some of the issues and
      therapies relating to cerebrovascular disease.

PMID- 18043779
TI  - The prescribing dilemma of benzodiazepines.
AB  - BACKGROUND: Benzodiazepines are the most commonly prescribed psychoactive drug in
      western societies. While associated with risk and harm, they have a legitimate
      place in therapeutics. Prescribing practice does not reflect guidelines and
      guidelines rarely provide the practical strategies required to manage the complex
      clinical management of conditions such as anxiety, insomnia and drug dependence.
      OBJECTIVE: This article proposes a model for rational prescribing of
      benzodiazepines that may be transferable to other therapeutic situations
      requiring the consideration of complex health, social and system factors.
      DISCUSSION: Benzodiazepines, like all psychoactive drugs, have their 'good',
      'bad' and 'ugly' side. Prescribing decisions are complex along the spectrum of
      use. Many subtle factors influence how each of us prescribe such as our knowledge
      of our patients, their medical histories, their personal situations and the
      individual doctor-patient relationship.

PMID- 18043780
TI  - Oral corticosteroids--their place in the management of adhesive capsulitis.
AB  - The incidence of intrinsic disorders of the shoulder presenting in general
      practice has been estimated to be 14.7/1000 per year with adhesive capsulitis
      (also termed frozen shoulder, stiff painful shoulder or periarthritis) accounting
      for around 20% of cases (incidence 2.4/1000 per year), but occurring more
      frequently in the middle aged and those with diabetes. The aetiology of
      pathological findings of intra-articular inflammation and fibrosis is not known.
      Adhesive capsulitis is diagnosed clinically based on characteristic symptoms and
      signs: spontaneous onset of severe shoulder pain that interferes with activities
      of daily living and sleep, and progressive stiffness or restriction of both
      active and passive movements, especially elevation and external rotation.

PMID- 18043781
TI  - Diagnostic dilemmas in unusual presentations of gout.
AB  - BACKGROUND: Gout is known to mimic conditions as diverse as joint and soft tissue
      infections, skin malignancies, nerve compression syndromes and soft tissue
      tumours. Upper limb involvement is unusual. OBJECTIVE: We discuss four cases of
      gout in the hand and wrist masquerading as a soft tissue tumour, nodular extensor
      tenosynovitis, septic arthritis of the wrist and acute and chronic median nerve
      compression. These cases illustrate that gout in the hand and wrist can resemble
      more sinister conditions, often posing a diagnostic challenge even to the
      experienced clinician. DISCUSSION: In the management of hand and wrist pain,
      swelling and neuropathy, emphasis must be placed on actively excluding limb and
      life threatening conditions such as septic arthritis and neoplasia. Laboratory
      and radiological investigations cannot accurately distinguish these pathologies
      from gout. Invasive surgical exploration or tissue sampling is often needed to
      establish the correct diagnosis.

PMID- 18043782
TI  - Impacts of alcohol use in pregnancy--the role of the GP.
AB  - BACKGROUND: Fetal alcohol syndrome (FAS) is a preventable cause of developmental
      delay and growth failure. OBJECTIVE: This article discusses the clinical features
      of fetal alcohol spectrum disorders (FASD) and the role of the general
      practitioner in prevention and management. DISCUSSION: Early diagnosis of and
      intervention for problems associated with FAS reduce adverse long term outcomes.
      Most health professionals have limited knowledge of FASD and lack confidence in
      the diagnosis and management of children with FASD. General practitioners have an
      important role in identifying women and children at risk of harm from alcohol and
      arranging referral for assessment and management when necessary. Educational
      materials for health professionals are currently under development.

PMID- 18043783
TI  - Failure to follow up CT reports.
AB  - Case histories are based on actual medical negligence claims or medicolegal
      referrals, however certain facts have been omitted or changed by the author to
      ensure the anonymity of the parties involved. A failure to follow up test results
      is a common underlying cause of medical negligence claims and complaints
      involving general practitioners. This article examines a case in which an
      incidental finding of an aneurysm on cerebral computerised tomography scan was
      not followed up with disastrous consequences for the patient.

PMID- 18043784
TI  - One family's stroke experience.
AB  - Eilish Rose Jukes was a healthy 3 1/2 year old. She contracted chicken pox mid
      April 2005 and recovered unremarkably, although her attention span and behaviour
      were out of character afterward.

PMID- 18043785
TI  - Occupational violence in general practice.
AB  - The risk of occupational violence is a cause for considerable concern in
      Australian general practice. Emerging evidence from Australian general practice
      is consistent with evidence from the United Kingdom that occupational violence is
      common and has important effects on practitioner welfare and delivery of care.
      This article provides an overview of the evidence of prevalence and impact of
      violence directed against GPs as a context for measures to increase the safety of
      GPs and their staff.

PMID- 18043786
TI  - An audit of INR control in the Australian indigenous setting.
AB  - BACKGROUND: Warfarin management can be difficult; many factors can impact on INR
      control with some factors being unique to the Australian indigenous setting.
      METHODS: An audit at an urban Aboriginal community controlled health service
      calculated the time all patients on warfarin were in the target INR therapeutic
      range. Those patients with the best and the worst values for time in therapeutic
      range (TTR) were then compared. RESULTS: The 26 identified patients on warfarin
      were in the target INR therapeutic range 44.9% of the time. Patients with better
      INR control were older than those with the worst control. There appeared to be no
      difference between the two groups when comparing other factors. DISCUSSION: INR
      control was below the cited benchmark for TTR of 60%. However, this may be better
      than expected in this clinical setting. The small number of patients included in
      the audit means that any discussion of the causes of better and poorer control
      must be treated with caution.

PMID- 18043787
TI  - Promoting patient centred palliative care through case conferencing.
AB  - BACKGROUND: What are the characteristics of case conferences between general
      practitioners and specialised palliative care services (SPCS)? METHODS: Study
      participants were adults (N=461) with pain in the preceding 3 months who were
      referred to a SPCS and their GPs (N=230). Patients were randomised to case
      conferences or routine care by SPCS. RESULTS: One hundred and sixty-seven
      conferences were held; 46 patients withdrew and 142 died before the conference
      could be conducted. Medicare payment was requested for 72 (43%) conferences.
      Median time from randomisation to case conference was 52 days (SD: 55), and from
      case conference to death/end of study was 79 days (SD: 166). Twenty-five percent
      of conferences had over three health professionals participant; patients and/or
      their caregivers participated in 91%. Average conference duration was 39 minutes
      (SD: 13). Mean conference length did not increase when more health professionals
      were present (3 vs. >3, 39 [SD: 14] vs. 42 [SD 11] minutes, p=0.274), nor when
      patients/caregivers were present (present vs. absent, 39 [SD: 13] vs. 44 [SD: 14]
      minutes, p=0.159). DISCUSSION: Case conferencing involving SPCS, the GP, other
      health professionals and the patient can be an efficient part of routine care.

PMID- 18043788
TI  - The psychosocial experience of women with PCOS--a case control study.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5-10%
      of women. It is characterised by androgenisation and anovulation, with sufferers
      being at increased risk of metabolic problems such as noninsulin dependent
      diabetes mellitus and dyslipidaemia. An increased risk of cardiovascular disease
      is speculated. Clinically, sufferers may experience acne, obesity, hirsutism
      and/or male pattern baldness.

PMID- 18043789
TI  - A risk score to diagnose depression in general practice.
AB  - BACKGROUND: Depression is a common mental health problem often seen in primary
      care. This study sought to determine the accuracy of five screening questions for
      diagnosing common mental disorders in a general practice clinic and to develop a
      risk score. METHODS: Three hundred and fifty patients not taking psychotropic
      drugs were evaluated using a combination of screening and confirmatory questions,
      a total symptom score, and a points system (employing multivariate statistical
      models) to quantify the ability of each question to detect a common mental
      disorder. RESULTS: Different screening and confirmatory strategies resulted in
      different sensitivities and specificities. There was good agreement between the
      risk estimate produced by the point system and that produced directly by the
      multivariate models. DISCUSSION: The point system developed to diagnose
      depression in the primary care setting is an alternative approach to currently
      available screening methods. It is easy to use but requires changes to the
      physician's approach to diagnostic certainty. The study needs to be replicated
      and the approach refined.

PMID- 18043790
TI  - Cancer education and training in primary health care--a national audit of
      training providers.
AB  - BACKGROUND: Primary care professionals play a critical role in cancer care but
      relatively little is known about their education and training. This article
      presents the results of a national audit of education and training providers in
      relation to primary care and cancer. METHOD: A semistructured telephone
      questionnaire. RESULTS: The response rate was very high (96%) with 210
      organisations participating. Forty-two percent provided cancer education and
      training. Evidence of good adult education practice was demonstrated, and 95% of
      organisations ran accredited programs. Although pharmaceutical industry support
      was not favoured, the majority (78%) described this as their main source of
      funding. DISCUSSION: There is optimism and strong commitment among primary care
      cancer education and training providers. Their content seems appropriate and
      their approach is consistent with good adult learning principles and
      multidisciplinary care, but this could be enhanced with increased funding and
      improved collaboration and communication between organisations.

PMID- 18043791
TI  - Generation, basic chemistry, and detection of N-nitrosotryptophan derivatives.
AB  - N-Terminal blocked tryptophan derivatives like melatonin or tryptophan residues
      in peptides are easily nitrosated at the nitrogen atom of the indole ring to give
      the corresponding N-nitrosotryptophan derivatives. This article provides a
      comprehensive view of the synthesis, chemical properties, and detection methods
      of this class of N-nitroso compounds of potential importance in biological
      systems.

PMID- 18043793
TI  - Nucleophilic activity of a linked bis{guanidine} leading to formation of a
      dicationic C4N4-heterocycle.
AB  - The methylene-linked bis{guanidine}, H(2)C{hpp}(2) (hppH = 1,3,4,6,7,8-hexahydro
      2H-pyrimido[1,2-a]pyrimidine), displays nucleophilic activity towards organic
      halides, including the activation of dichloromethane under ambient conditions
      affording the cyclic dication, [H(2)C{hpp}(2)CH(2)](2+)[Cl](2).

PMID- 18043792
TI  - Alpha-substituted organic peroxides: synthetic strategies for a biologically
      important class of gem-dihydroperoxide and perketal derivatives.
AB  - In this paper we review the recent developments in the synthesis of alpha
      substituted hydroperoxides. Alpha-substituted hydroperoxides are interesting
      compounds due to their chemistry and bioactivity and as intermediates for the
      synthesis of other peroxides, of which cyclic peroxides are of major importance.
      Although the emphasis of this report will be on the derivatives of gem
      dihydroperoxides, perketals, as well as the less studied nitrogen and sulfur
      derivatives, will also be covered.

PMID- 18043794
TI  - Chemical properties of fatty acid derivatives as inhibitors of DNA polymerases.
AB  - In this study, the chemical properties of organic acids as DNA polymerase
      inhibitors were examined. In total, we assayed the inhibitory activities of 23
      compounds. We found that the DNA synthesis activity of DNA polymerase was usually
      reduced to less than 50% in the presence of 100 microM monoprotic acids, which
      have a Clog P value greater than 7.0 and a pK(a) value less than 5.4. With a
      minor modification these chemical properties applied to several organic fatty
      acids previously reported as DNA polymerase inhibitors. Moreover, we also
      examined the inhibitory activities of perfluorooctadecanoic acid (PFOdA) and
      perfluorooctanesulfonic acid (PFOS) against DNA polymerase beta in detail. These
      compounds inhibited the polymerase activity of pol beta competitively with
      template-primer DNA, and non-competitively with dNTPs. In addition, the 8 kDa
      domain-defective pol beta was also sensitive to these compounds. Our results
      suggest that the inhibitory mode of action of PFOdA and PFOS is different from
      that mediated by the classic fatty acid inhibitors against DNA polymerase beta.

PMID- 18043795
TI  - Asymmetric synthesis of beta-amino-gamma-substituted-gamma-butyrolactones: double
      diastereoselective conjugate addition of homochiral lithium amides to homochiral
      alpha,beta-unsaturated esters.
AB  - Chiral alpha,beta-unsaturated esters, containing a single, gamma-stereogenic
      centre, show modest levels of substrate control upon conjugate addition of
      lithium dibenzylamide. Double diastereoselective conjugate additions of
      homochiral lithium N-benzyl-N-(alpha-methylbenzyl)amide to the homochiral
      alpha,beta-unsaturated esters display "matching" and "mismatching" effects. In
      each case, however, these additions proceed under the dominant stereocontrol of
      the lithium amide to give the corresponding beta-amino esters in high de. A
      remarkable reversal in stereoselectivity is noted by changing the ester
      functionality to an oxazolidinone. Subsequent O-deprotection and cyclisation of
      the resultant beta-amino adducts gives access to the corresponding beta-amino
      gamma-substituted-gamma-butyrolactones in good yield and high de.

PMID- 18043796
TI  - Enantioselective Henry reaction catalyzed by a C2-symmetric bis(oxazoline)
      Cu(OAc)2.H2O complex.
AB  - A C(2)-symmetric diethyl (i)Pr-bis(oxazoline)-Cu(OAc)(2).H(2)O was found to be an
      efficient catalyst for catalyzing an enantioselective Henry reaction between
      nitromethane and various aldehydes to provide beta-hydroxy nitroalkanes with high
      chemical yields (up to 95%) and enantiomeric excesses (up to 97%).

PMID- 18043797
TI  - Multi-component orbital interactions during oxyacyl radical addition reactions
      involving imines and electron-rich olefins.
AB  - Ab initio and DFT calculations reveal that oxyacyl radicals add to imines and
      electron-rich olefins through simultaneous SOMO-pi*, SOMO-pi and pi*-HOMO
      interactions between the radical and the radicalophile. At the BHandHLYP/aug-cc
      pVDZ level, energy barriers of 20.3 and 22.0 kJ mol(-1) are calculated for the
      attack of methoxycarbonyl radical at the carbon and nitrogen ends of methanimine,
      respectively. In comparison, barriers of 22.0 and 8.6 kJ mol(-1) are calculated
      at BHandHLYP/aug-cc-pVDZ for reaction of methoxycarbonyl radical at the 1- and 2
      positions in aminoethylene, respectively. Natural bond orbital (NBO) analysis at
      the BHandHLYP/6-311G** level of theory reveals that SOMO-pi*, SOMO-pi and pi*-LP
      interactions are worth 111, 394 and 55 kJ mol(-1) respectively in the transition
      state (8) for reaction of oxyacyl radical at the nitrogen end of methanimine;
      similar interactions are observed for the chemistry involving aminoethylene.
      These multi-component interactions are responsible for the unusual motion vectors
      associated with the transition states involved in these reactions.

PMID- 18043798
TI  - Kinetics and mechanism of the aminolysis of aryl ethyl chloro and chlorothio
      phosphates with anilines.
AB  - The reactions of ethyl Y-phenyl chloro (1) and chlorothio (2) phosphates with X
      anilines in acetonitrile at 55.0 degrees C are studied kinetically and
      theoretically. Kinetic results yield the primary kinetic isotope effects
      (k(H)/k(D) = 1.07-1.80 and 1.06-1.27 for 1 and 2, respectively) with deuterated
      aniline (XC(6)H(4)ND(2)) nucleophiles, and the cross-interaction constants
      rho(XY) = -0.60 and -0.28 for and , respectively. A concerted mechanism involving
      a partial frontside attack through a hydrogen-bonded, four-center-type transition
      state is proposed. The large rho(X) (rho(nuc) = -3.1 to -3.4) and beta(X)
      (beta(nuc) = 1.1-1.2) values seem to be characteristic of the anilinolysis of
      phosphates and thiophosphates with the Cl leaving group. Because of the
      relatively large size of the aniline nucleophile, the degree of steric hindrance
      could be the decisive factor that determines the direction of the nucleophilic
      attack to the phosphate and thiophosphate substrates with the relatively small
      sized Cl leaving group.

PMID- 18043799
TI  - Nitroxyl radicals: electrochemical redox behaviour and structure-activity
      relationships.
AB  - Comparative study of electrochemical redox behaviour of five different nitroxyl
      radicals leads to the direct correlation between one-electron redox potentials
      and group electronegativity of the beta-substituent on the ring. Beta
      substituents with an electron-donating effect caused a negative shift in the one
      electron oxidation and one-electron reduction potentials of the nitroxyl
      radicals. In a similar aspect, beta-substituents with an electron-withdrawing
      effect behaved oppositely.

PMID- 18043800
TI  - Intramolecular cyclization of beta,beta-difluorostyrenes bearing an iminomethyl
      or a diazenyl group at the ortho position: synthesis of 3-fluorinated
      isoquinoline and cinnoline derivatives.
AB  - o-Formyl-substituted beta,beta-difluorostyrenes readily react with NH(2)OH.HCl or
      NH(4)OAc to afford 3-fluoroisoquinoline derivatives in good yield via (i) the
      formation of the corresponding oximes or imines and (ii) subsequent
      intramolecular replacement of a vinylic fluorine by the sp(2) nitrogen of the
      iminomethyl group (HON=CH- or HN=CH-). Beta,beta-Difluorostyrenes bearing an o
      diazenyl group (HN=N-), generated by reduction of the corresponding diazonium
      ions, undergo a similar substitution to afford 3-fluorinated cinnolines.

PMID- 18043801
TI  - Pyrazole carboxamides and carboxylic acids as protein kinase inhibitors in
      aberrant eukaryotic signal transduction: induction of growth arrest in MCF-7
      cancer cells.
AB  - Densely functionalised pyrazole carboxamides and carboxylic acids were
      synthesised in an expedient manner through saponification and transamidation,
      respectively, of ester-functionalised pyrazoles. This synthetic protocol allowed
      for three diversifying steps in which appendages on the pyrazole scaffold were
      adjusted to optimise inhibition of protein kinases. Thirty-five analogues were
      tested in CK2, AKT1, PKA, PKCalpha, and SAPK2a (p38) kinase inhibition bioassays.
      Blocking of these kinases may lead to effective therapies for treating
      inflammatory diseases and cancer. In order to investigate potential biological
      activity, MCF-7 human breast cancer cells were incubated with the most promising
      derivatives. Two analogues caused changes in MCF-7 cell growth, one of them
      through cell cycle arrest demonstrated by cell cycle analysis.

PMID- 18043802
TI  - Glycosynthase activity of hybrid aspen xyloglucan endo-transglycosylase PttXET16
      34 nucleophile mutants.
AB  - Glycosynthases are active-site mutants of glycoside hydrolases that catalyse
      glycosyl transfer using suitable activated donor substrates without competing
      product hydrolysis (S. M. Hancock, M. D. Vaughan and S. G. Withers, Curr. Opin.
      Chem. Biol., 2006, 10, 509-519). Site-directed mutagenesis of the catalytic
      nucleophile, Glu-85, of a Populus tremula x tremuloides xyloglucan endo
      transglycosylase (PttXET16-34, EC 2.4.1.207) into alanine, glycine, and serine
      yielded enzymes with glycosynthase activity. Product analysis indicated that
      PttXET16-34 E85A in particular was able to catalyse regio- and stereospecific
      homo- and hetero-condensations of alpha-xylogluco-oligosaccharyl fluoride donors
      XXXGalphaF and XLLGalphaF to produce xyloglucans with regular sidechain
      substitution patterns. This substrate promiscuity contrasts that of the Humicola
      insolens Cel7B E197A glycosynthase, which was not able to polymerise the di
      galactosylated substrate XLLGalphaF. The production of the PttXET16-34 E85A
      xyloglucosynthase thus expands the repertoire of glycosynthases to include those
      capable of synthesising structurally homogenenous xyloglucans for applications.

PMID- 18043803
TI  - Pericosines, antitumour metabolites from the sea hare-derived fungus Periconia
      byssoides. Structures and biological activities.
AB  - Pericosines A-E 1-5 have been isolated from a strain of Periconia byssoides
      originally separated from the sea hare Aplysia kurodai. Among them, pericosines C
      3 and E 5 were separated as enantiomeric mixtures. Their stereostructures, except
      for compound 1, have been elucidated or identified on the basis of spectroscopic
      analyses, including 1D and 2D NMR techniques, and X-ray analysis. In addition,
      conformation for all the compounds has been discussed. Compounds 1-3 exhibited
      significant growth inhibition against tumour cell lines. Pericosine A 1 also
      showed significant in vivo tumour inhibitory activity. In addition, compound
      inhibited the protein kinase EGFR and topoisomerase II.

PMID- 18043804
TI  - Synthesis, photophysical properties and in vitro photodynamic activity of axially
      substituted subphthalocyanines.
AB  - A new series of subphthalocyanines substituted axially with an oligoethylene
      glycol chain [SPcB(OCH(2)CH(2))(n)OH, n = 3 (2) or 4 (3)] or a p-phenoxy
      oligoethylene glycol methyl ether chain [SPcBOC(6)H(4)(OCH(2)CH(2))(n)OCH(3), n =
      2 (4) or 3 (5)] have been synthesised by substitution reactions of boron
      subphthalocyanine chloride SPcBCl (1) with the corresponding oligoethylene
      glycols, and characterised with various spectroscopic methods and elemental
      analysis. The molecular structure of one of these compounds (subphthalocyanine 4)
      has also been determined. As revealed by absorption spectroscopy, these compounds
      are essentially non-aggregated in DMF. The low aggregation tendency of these
      compounds results in a strong fluorescence emission and high efficiency to
      generate singlet oxygen. All these subphthalocyanines, being formulated with
      Cremophor EL, function as efficient photosensitisers and exhibit a high
      photocytotoxicity against HepG2 human hepatocarcinoma and HT29 human colon
      adenocarcinoma cells. The phenoxy analogues 4 and 5 show a relatively high
      photostability and are particularly potent towards these cell lines, with IC(50)
      values down to 0.02 microM.

PMID- 18043805
TI  - Reactivity and selectivity in the inhibition of elastase by 3-oxo-beta-sultams
      and in their hydrolysis.
AB  - 3-oxo-beta-sultams are both beta-sultams and beta-lactams and are a novel class
      of time-dependent inhibitors of elastase. The inhibition involves formation of a
      covalent enzyme-inhibitor adduct with transient stability by acylation of the
      active-site serine resulting from substitution at the carbonyl centre of the 3
      oxo-beta-sultam, C-N fission, and expulsion of the sulfonamide. The lead
      compound, N-benzyl-4,4-dimethyl-3-oxo-beta-sultam 1 is a reasonably potent
      inhibitor against porcine pancreatic elastase with a second-order rate constant
      of 768 M(-1) s(-1) at pH 6, but also possesses high chemical reactivity with a
      half-life for hydrolysis of only 6 mins at the same pH in water. Interestingly,
      the hydrolysis of 3-oxo-beta-sultams occurs at the sulfonyl centre with S-N
      fission and expulsion of the amide leaving group, whereas the enzyme reaction
      occurs at the acyl centre. Increasing selectivity between these two reactive
      centres was explored by examining the effect of substituents on the reactivity of
      3-oxo-beta-sultam towards hydrolysis and enzyme inhibition. The inhibition
      activity against porcine pancreatic elastase has a much higher sensitivity to
      substituent variation than does the rate of alkaline hydrolysis. A difference of
      2000-fold is observed in the second-order rate constants, k(i), for inhibition
      whereas there is only a 100-fold difference in the second-order rate constants,
      k(OH), for alkaline hydrolysis within the series. The higher sensitivity of
      enzyme inhibition to substituents than that of simple chemical reactivity
      indicates a significant degree of molecular recognition of the 3-oxo-beta-sultams
      by the enzyme.

PMID- 18043807
TI  - Iodine assisted palladium catalyzed ring opening of bicyclic hydrazines with
      organoboronic acids: stereoselective synthesis of functionalized cyclopentenes
      and alkylidene cyclopentenes.
AB  - A novel reactivity of organoboronic acids with bicyclic hydrazines leading to the
      stereoselective formation of trans-vicinal disubstituted cyclopentenes in good to
      excellent yield is discussed. The reaction of cyclopentadiene and fulvene derived
      azabicyclic alkenes with organoboronic acids afforded the trans-3,4-disubstituted
      cyclopentenes and alkylidene cyclopentenes in good to excellent yields. The
      products, having a broad range of substituents, are important intermediates in
      the synthesis of a number of pharmaceutically important molecules.

PMID- 18043806
TI  - Experimental and computational evidence for alpha-lactone intermediates in the
      addition of aqueous bromine to disodium dimethyl-maleate and -fumarate.
AB  - Structural analysis of the bromo-beta-lactones obtained by addition of bromine to
      aqueous solutions of disodium 2,3-dimethylmaleate and 2,3-dimethylfumarate
      reveals stereochemistries opposite to those originally assigned in 1937: cis
      alkene yields erythro lactone, and trans alkene yields threo lactone. B3LYP/6
      31+G(d) calculations using a PCM description of aqueous solvation confirm the
      validity of our proposed mechanism, in which the first-formed intermediate in
      each case is an alpha-lactone. The cyclic bromonium species is not an
      intermediate. An alternative pathway leading directly from cis alkene to cis
      lactone, via an unusual frontside displacement mechanism, is over 20 kJ mol(-1)
      higher in free energy. Hydrolysis of the bromo-beta-lactones yields bromohydrins
      whose stereochemistries as determined by X-ray crystallography indicate
      stereospecific formation by acyl-oxygen cleavage of the lactone ring, again
      contrary to the original view.

PMID- 18043809
TI  - Novel enzyme/DNA/inorganic nanomaterials: a new generation of biocatalysts.
AB  - The design, synthesis and properties of a new class of enzyme/DNA/inorganic
      nanobiomaterials are described here. DNA has been used to stabilize the enzymes
      intercalated in the galleries of the inorganic solid, alpha-Zr(iv) phosphate
      (alpha-Zr(HPO(4))(2).H(2)O, abbreviated as alpha-ZrP). Interestingly, the
      presence of DNA improved the activity and stability of the bound enzymes. Key
      studies leading to the current strategy are presented initially, and these are
      followed by more recent developments. Several enzymes and proteins, including
      horseradish peroxidase, lysozyme, glucose oxidase, chymotrypsin, bovine serum
      albumin, cytochrome c, met-hemoglobin and met-myoglobin are successfully
      intercalated in the galleries of alpha-ZrP, under benign ambient conditions
      (aqueous buffered solutions, at room temperature and neutral pH). These novel
      materials are characterized by XRD, SEM and TEM as well as by biochemical,
      calorimetric and spectroscopic methods. Spectroscopic studies (circular
      dichroism, CD), for example, indicated that co-intercalation of DNA improved the
      retention of bound enzyme structure. The activity was enhanced markedly (five
      fold) when DNA is co-intercalated, when compared to the activity in the absence
      of DNA. Addition of DNA to the sample, after enzyme intercalation, did not make
      any improvements. Our hypothesis is that enzyme-DNA supramolecular complex binds
      to the solid and the unfavorable interactions between the enzyme and the solid
      are minimized. These novel nanobiocomposite materials provide a simple method for
      packaging DNA and aid in engineering more effective synthetic materials for
      gene/RNA-delivery and drug delivery applications.

PMID- 18043810
TI  - Design and understanding of heterogeneous alkene metathesis catalysts.
AB  - This review outlines the molecular insights provided by surface organometallic
      chemistry in the area of alkene metathesis, and particularly in the development
      and the understanding of heterogeneous catalysts.

PMID- 18043811
TI  - Phosphinines as ligands in homogeneous catalysis: recent developments, concepts
      and perspectives.
AB  - Phosphinines belong to an intriguing class of phosphorus-containing heterocycles
      with interesting steric, electronic and coordinating properties. This article
      focuses on recent developments, concepts and perspectives in the field of
      phosphinines and phosphinine-based ligands and their application as ligands in
      homogeneous catalytic reactions.

PMID- 18043812
TI  - Pd-catalysed methoxycarbonylation of vinylarenes using chiral monodentate
      phosphetanes and phospholane as ligands. Effect of substrate substituents on
      enantioselectivity.
AB  - Palladium complexes bearing phospholane 1 and phosphetane 2-4 ligands have been
      synthesised to be used as catalyst precursors in the asymmetric
      methoxycarbonylation of vinyl arenes. Single crystals of the complex [PdCl2(2)2]
      II were obtained from a toluene solution and analysed by X-ray crystallography.
      Using these complexes, excellent regioselectivity (up to 99%) to the branched
      esters was obtained. Phosphetane ligands provide higher enantioselectivity than
      the phospholane under the same reaction conditions and an important influence of
      the substrate was observed. Enantioselectivity up to 50% was obtained using 4
      methoxystyrene.

PMID- 18043813
TI  - "Solventless" continuous flow homogeneous hydroformylation of 1-octene.
AB  - The hydroformylation of 1-octene under continuous flow conditions is described.
      The system involves dissolving the catalyst, made in situ from [Rh(acac)(CO)(2)]
      (acacH=2,4-pentanedione) and [RMIM][TPPMS] (RMIM=1-propyl (Pr), 1-pentyl (Pn) or
      1-octyl (O) -3-methyl imidazolium, TPPMS=Ph(2)P(3-C(6)H(4)SO(3))), in a mixture
      of nonanal and 1-octene and passing the substrate, 1-octene, together with CO and
      H(2) through the system dissolved in supercritical CO(2) (scCO(2)).
      [PrMIM][TPPMS] is poorly soluble in the medium so heavy rhodium leaching (as
      complexes not containing phosphine) occurs in the early part of the reaction.
      [PnMIM][TPPMS] affords good rates at relatively low catalyst loadings and
      relatively low overall pressure (125 bar) with rhodium losses <1 ppm, but the
      catalyst precipitates at higher catalyst loadings, leading to lower reaction
      rates. [OMIM][TPPMS] is the most soluble ligand and promotes high reaction rates,
      although preliminary experiments suggested that rhodium leaching was high at 5-10
      ppm. Optimisation aimed at balancing flows so that the level within the reactor
      remained constant involved a reactor set up based around a reactor fitted with a
      sight glass and sparging stirrer with the CO(2) being fed by a cooled head HPLC
      pump, 1-octene by a standard HPLC pump and CO/H(2) through a mass flow
      controller. The pressure was controlled by a back pressure regulator. Using this
      set up, [OMIM][TPPMS] as the ligand and a total pressure of 140 bar, it was
      possible to control the level within the reactor and obtain a turnover frequency
      of ca. 180 h(-1). Rhodium losses in the optimised system were 100 ppb. Transport
      studies showed that 1-octene is preferentially transported over the aldehydes at
      all pressures, although the difference in mol fraction in the mobile phase was
      less at lower pressures. Nonanal in the mobile phase suppresses the extraction of
      1-octene to some extent, so it is better to operate at high conversion and low
      pressure to optimise the extraction of the products relative to the substrate. CO
      and H(2) in the mobile phase also suppress the extraction efficiency by as much
      as 80%.

PMID- 18043814
TI  - Chiral manganese complexes with pinene appended tetradentate ligands as
      stereoselective epoxidation catalysts.
AB  - A novel family of chiral manganese complexes Lambda-1(CF(3)SO(3)) and Delta
      2(CF(3)SO(3)), have been stereoselectively prepared, characterized and studied as
      epoxidation catalysts. The complexes are structurally related to
      [Mn(II)(CF(3)SO(3))(2)(alpha-MCP)] (MCP=N,N'-dimethyl-N,N'-bis(2
      pyridylmethyl)cyclohexane-trans-1,2-diamine), recently reported as a very
      efficient epoxidation catalyst in combination with peracetic acid. Pinene rings
      have been fused to the 4 and 5 positions of the two pyridine groups of the
      ligand, giving rise to complexes where the two labile binding sites of the
      manganese ion are confined in a better-defined chiral pocket than in the parent
      [Mn(II)(CF(3)SO(3))(2)(alpha-MCP)]. Chirality in these complexes arises from the
      stereochemistry of the trans-diaminocyclohexane ring, from the pinene ring and
      also from the topological chirality adopted by the ligand upon binding to the
      manganese ion. While previous studies have demonstrated that small modifications
      in the structure of the MCP ligand result in a dramatic loss of efficiency,
      Lambda-1(CF(3)SO(3)) and Delta-2(CF(3)SO(3)) exhibit comparable catalytic
      activity to [Mn(II)(CF(3)SO(3))(2)(alpha-MCP)]. In addition, the complexes
      exhibit a remarkable stereoselectivity (up to 46% ee) in the epoxidation of
      selected substrates. The results reported in this work point towards modification
      of the 4 and 5 positions of the pyridine groups as a new strategy towards the
      design of stereoselective versions of this family of highly active and
      environmentally benign epoxidation catalysts.

PMID- 18043815
TI  - Access to well-defined isolated Fe(II) centers on silica and their use in
      oxidation.
AB  - Well-defined Fe(II) isolated sites are obtained by reaction of diaryl-N,N'
      diazadiene bis(neosilyl) iron (1) with an aerosil silica, SiO(2-(700)). This
      system can be used as a precursor for the catalytic oxidation of cyclohexene into
      cyclohexene oxide, cyclohexenol and cyclohexenone in the presence of H(2)O(2).

PMID- 18043816
TI  - Supported ionic liquid phase rhodium nanoparticle hydrogenation catalysts.
AB  - Rh(0) nanoparticles (ca. 4 nm) dispersed in an ionic liquid (1-n-butyl-3
      methylimidazolium tetrafluoroborate) were immobilized within a silica network,
      prepared by the sol-gel method. The effect of the sol-gel catalyst (acid or base)
      on the encapsulated ionic liquid and Rh(0) content, on the silica morphology and
      texture, and on the catalyst alkene hydrogenation activity was investigated. The
      Rh(0) content in the resulting xerogels (ca. 0.1 wt% Rh/SiO(2)) was shown to be
      independent of the sol-gel process. However, acidic conditions afforded higher
      contents of encapsulated ionic liquid and xerogels with larger pore diameters,
      which in turn might be responsible for the higher catalyst activity in
      hydrogenation of the alkenes.

PMID- 18043817
TI  - On the involvement of NHC carbenes in catalytic reactions by iridium complexes,
      nanoparticle and bulk metal dispersed in imidazolium ionic liquids.
AB  - D/H exchange reactions at C2, C4 and C5 of the imidazolium cation were observed
      in catalytic hydrogenation reactions promoted by classical Ir(I) colloid
      precursors and [Ir(0)](n) nanoparticles dispersed in deuterated imidazolium ionic
      liquids indicating the participation of carbene species in this media. However,
      no D/H exchange reaction was observed in cyclohexene hydrogenation promoted by
      iridium bulk metal dispersed in the ionic liquid [BMI]-d(3).NTf(2). The D/H
      labeling experiments suggest that the ionic liquids interact with the metal
      centers preferentially as aggregates rather than isolated ions.

PMID- 18043818
TI  - Lithium complexes supported by amine bis-phenolate ligands as efficient catalysts
      for ring-opening polymerization of L-lactide.
AB  - Lithium complexes bearing dianionic amine bis(phenolate) ligands are described.
      Reactions of ligand precursors H(2)O(2)NN(Me), H(2)O(2)NN(Py) or H(2)O(2)NO(Me)
      [H(2)O(2)NN(Me)=Me(2)NCH(2)CH(2)N-(CH(2)-2-HO-3,5-C(6)H(2)((t)Bu)(2))(2);
      H(2)O(2)NN(Py)=(2-C(5)H(4)N)CH(2)N-(CH(2)-2-HO-3,5-C(6)H(2)((t)Bu)(2))(2);
      H(2)O(2)NO(Me)=MeOCH(2)CH(2)N-(CH(2)-2-HO-3,5-C(6)H(2)((t)Bu)(2))(2)] with 2.2
      molar equivalents of (n)BuLi in diethylether afford (Li(2)O(2)NN(Me))(2) (1),
      (Li(2)O(2)NN(Py))(2) (2) and (Li(2)O(2)NO(Me))(2) (3) as tetra-nuclear lithium
      complexes. The crystalline solids of partially hydrolyzed product,
      (LiO(HO)NN(Py)) (4), were obtained from recrystallization of 2 in diethylether
      solution for three months. The synthesis of (LiO(HO)NO(Me))(2) (5) was carried
      out at ambient temperature by carefully layering a solution of water in hexane on
      top of a solution of 3 in Et(2)O. Crystalline solids of were obtained after two
      months. Molecular structures are reported for compounds 1, 3, 4 and 5. Compounds
      1-3 show excellent catalytic activities toward the ring-opening polymerization of
      L-lactide in the presence of benzyl alcohol.

PMID- 18043819
TI  - Ansa-bridged eta5-cyclopentadienyl molybdenum and tungsten complexes: synthesis,
      structure and application in olefin epoxidation.
AB  - Ansa-bridged eta(5)-cyclopentadienyl molybdenum and tungsten tricarbonyl
      complexes of formula [M(eta(5)-C(5)H(4)(CH(2))(3)-eta(1)-CH(2))(CO)(3)] (M=Mo or
      W) were synthesized and the X-ray crystal structure of the tungsten complex is
      reported. In the epoxidation of cyclooctene the molybdenum compound shows a high
      catalytic activity, approaching the observed activities for the most reactive
      unbridged complexes of composition CpMo(CO)(3)X (X=Cl, CH(3)). The activity of
      the tungsten complex is also amongst the highest catalytic activities for the
      olefinic epoxidation of complexes with the composition CpW(CO)(3)X and
      WO(2)X(2)L(2), reported so far. The low ring strain of the ansa-bridged system
      improves the stability of the complexes under oxidative conditions considerably
      in comparison to derivatives with a shorter bridge and therefore paves the way to
      introduction of chirality in these systems.

PMID- 18043820
TI  - Palladium catalyzed Suzuki C-C couplings in an ionic liquid: nanoparticles
      responsible for the catalytic activity.
AB  - A new family of functionalized ligands derived from norborn-5-ene-2,3
      dicarboxylic anhydride has been used in Suzuki C-C cross-couplings between aryl
      boronic acids and aryl bromide derivatives in [BMI][PF(6)] (BMI=1-n-butyl-3
      methyl-imidazolium), using palladium acetate as catalytic precursor. High
      conversions and yields are obtained when amine ligands containing hydroxy groups
      are involved. TEM analyses after catalysis show the formation of small
      nanoparticles, in contrast to the agglomerates observed when nanoparticles are
      intentionally preformed, with a consequent decrease in the catalytic activity in
      the latter case. Some tests, including the correlation effect between solvent and
      ligand, are carried out to try to identify the true nature of the catalyst. All
      the results obtained suggest that formation of nanoparticles is required to lead
      to a catalytically active system.

PMID- 18043821
TI  - Evaluation of C4 diphosphine ligands in rhodium catalysed methanol carbonylation
      under a syngas atmosphere: synthesis, structure, stability and reactivity of
      rhodium(I) carbonyl and rhodium(III) acetyl intermediates.
AB  - The carbonylation of methanol to acetic acid is a hugely important catalytic
      process, and there are considerable cost and environmental advantages if a
      process could be designed that was tolerant of hydrogen impurities in the CO feed
      gas, while eliminating by-products such as propionic acid and acetaldehyde
      altogether. This paper reports on an investigation into the application of
      rhodium complexes of several C(4) bridged diphosphines, namely BINAP, 1,4
      bis(diphenylphosphino)butane (dppb), bis(diphenylphosphino)xylene (dppx) and 1,4
      bis(dicyclohexylphosphino)butane (dcpb) as catalysts for hydrogen tolerant
      methanol carbonylation. An investigation into the structure, reactivity and
      stability of pre-catalysts and catalyst resting states of these complexes has
      also been carried out in order to understand the observations in catalysis. Rh(I)
      carbonyl halide complexes of each of the ligands have been prepared from both
      [Rh(2)(CO)(4)Cl(2)] and dimeric mu-Cl-[Rh(L)Cl](2) complexes. These Rh(I)
      carbonyl complexes are either dimeric with bridging phosphine ligands (dppb,
      dcpb, dppx) or monomeric chelate complexes. The reaction of the complexes with
      methyl iodide at 140 degrees C has been studied, which has revealed clear
      differences in the stability of the corresponding Rh(III) complexes.
      Surprisingly, the dimeric Rh(I) carbonyls react cleanly with MeI with
      rearrangement of the diphosphine to a chelate co-ordination mode to give stable
      Rh(III) acetyl complexes. The Rh acetyls for L=dppb and dppx have been fully
      characterised by X-ray crystallography. During the catalytic studies, the more
      rigid dppx and BINAP ligands were found to be nearly 5 times more hydrogen
      tolerant than [Rh(CO)(2)I(2)](-), as revealed by by-product analysis. The origin
      of this hydrogen tolerance is explained based on the differing reactivities of
      the Rh acetyls with hydrogen gas, and by considering the structure of the
      complexes.

PMID- 18043822
TI  - Ligand effects in the non-alternating CO-ethylene copolymerization by
      palladium(II) catalysis.
AB  - In this paper we report on a comparative study of the non-alternating CO-C(2)H(4)
      copolymerization catalyzed by neutral Pd(II) complexes with the phosphine
      sulfonate ligands bis(o-methoxyphenyl)phosphinophenylenesulfonate and bis(o
      methoxyphenyl)phosphino-ethylenesulfonate. The former ligand, featuring a lower
      skeletal flexibility, has been found to form more active catalysts as well as
      produce polyketones with higher molecular weight and higher extra-ethylene
      incorporation. Operando high-pressure NMR studies have allowed us to intercept,
      for the first time, Pd(II)(phosphine-sulfonate) beta-chelates in the non
      alternating copolymerization cycle, while model organometallic reactions have
      contributed to demonstrate that Pd(II) (phosphine-sulfonate) fragments do not
      form stable carbonyl complexes. The opening of the beta-chelates has been found
      to be a viable process by either comonomer, which contrasts with the behaviour of
      Pd(II) (chelating diphosphine) catalysts for the perfectly alternating
      copolymerization.

PMID- 18043823
TI  - Development of pinene-derived N,P ligands and their utility in catalytic
      asymmetric hydrogenation.
AB  - New diastereomeric N,P-ligands, derived from the natural product (+)-alpha
      pinene, have been synthesized and evaluated in iridium-catalyzed asymmetric
      hydrogenation. The ligands are tetrahydroquinoline derivatives synthesized
      directly from commercially available alpha-pinene utilizing resolution or
      recrystallization to separate diastereomers. In reduction of a range of different
      trisubstituted alkenes the catalysts express very different activities ranging
      from no activity to high activity. One of the catalysts gives good ee values for
      some substrates.

PMID- 18043824
TI  - Primary umbilical adenocarcinoma.
AB  - Primary umbilical tumours are extremely rare. We report primary serous
      adenocarcinoma arising from the coelomic mesothelium of the hernial sac. A 60
      year-old woman presented with an umbilical swelling of six months duration that
      became painful in the last three days. Examination revealed a tender umbilical
      swelling diagnosed as obstructive hernia that needed surgery. When dissecting the
      sac during surgery, a small subcutaneous abscess was encountered. The sac
      contained an omentum with a hard nodule at the surface which was excised.
      Umbilical hernia repair was performed. Histology of the omental nodule revealed
      serous papillary adenocarcinoma. Chest and abdomen computed tomography, pelvic
      magnetic resonance imaging, gastroscopy, colonoscopy and laparotomy did not
      reveal the primary site of the tumour.

PMID- 18043825
TI  - Adenocarcinoma of the rete testis with uncommon presentation as haematocele.
AB  - Adenocarcinoma of the rete testis was encountered in a 62-year-old man. The
      tumour was localised in the region of the testicular hilum as a greyish-white
      nodule that showed no involvement of the adjacent testicular parenchyma or the
      epididymis. On microscopical examination, there was a well-differentiated
      adenocarcinoma separated by fibrovascular stroma, entirely confined to the
      testicular hilum. This primary carcinoma of the rete testis presented as a
      haematocele.

PMID- 18043826
TI  - The patella as an unusual site of renal cell carcinoma metastasis.
AB  - We report a rare case of renal cell carcinoma with metastasis to the patella in a
      49-year-old man, who presented with seven months of left knee pain after a fall.
      Only two similar cases have been reported. Patellar metastasis is rare because it
      has a relatively poor blood supply and microemboli would have been sieved out by
      the pulmonary circulation. Patellectomy is the usual treatment for such cases. We
      suspect that the preferential metastasis in our patient is a result of tropism.
      Our treatment for this patient is unique. We opted for a patella-preserving
      operation involving the use of cryotherapy, as this treatment modality preserved
      the quality of life. An opportunistic biopsy one year later confirmed the absence
      of active disease within the patella. This case uniquely provides human in vivo
      histological confirmation that an intralesional procedure with local and systemic
      adjuvant therapy effectively controls local disease.

PMID- 18043827
TI  - Malignant pancreatic carcinoid tumour.
AB  - Pancreatic carcinoid tumours are rare, particularly within the paediatric
      population. The clinical presentation is largely dependent on the functionality
      of the tumour. Although the tumour is generally slow-growing, surgical resection
      is still the mainstay of curative treatment. Morbidity is, however, significantly
      contributed by secretion of excess hormones; in view of this, biotherapy is an
      important treatment strategy. Octreotide, a somatostatin analogue, has been shown
      to be successful in both symptomatic control and stability of tumour progression.
      We report a 12-year-old girl, who presented with hypertensive crisis, and showed
      good response to a combination of chemotherapy and octreotide.

PMID- 18043828
TI  - Management of extensive subcutaneous emphysema and pneumomediastinum by micro
      drainage: time for a re-think?
AB  - Extensive subcutaneous emphysema (ESE) is not only disfiguring, uncomfortable and
      alarming for the patient, but can rarely be associated with airway compromise,
      respiratory failure and death. Traditionally considered a cosmetic nuisance, few
      reports on interventions to relieve ESE exist. Most interventions are too
      invasive and have not been widely used. Fenestrated catheters have been reported
      to be effective in ESE. We report our experience on microdrainage with a
      fenestrated catheter and compressive massage in a 50-year-old man with ESE
      following pigtail insertion for drainage of lung abscess. The apparatus is easily
      constructed and the procedure is simple, painless, minimally invasive, highly ef
      fective and cosmetically aesthetic. Placement of an underwater trap and
      visualisation of bubbling can be used as end-points for adequate compressive
      massage. Routine management with this catheter can be considered as the procedure
      of choice for ESE.

PMID- 18043829
TI  - Pulmonary infections mimicking cancer: report of four cases.
AB  - Lung infections infrequently simulate cancer, and their differentiation, based on
      imaging findings, can sometimes be difficult. The infections may be fungal,
      mycobacterial, parasitic or, rarely, viral. A biopsy is required to prove the
      infectious nature of the lesions. A specific diagnosis is necessary for
      initiation of appropriate therapy. We report four cases of chronic pulmonary
      infections, which were wrongly diagnosed as bronchogenic carcinoma based on
      radiological features. We also reviewed the existing literature.

PMID- 18043830
TI  - Arched left gonadal artery over the left renal vein associated with double left
      renal artery.
AB  - Variations in the anatomical relationship of the gonadal arteries to the renal
      vessels are frequently reported. We present, on a male cadaver, an unusual origin
      and course of a left testicular artery arching over the left renal vein along
      with double renal arteries. The development of this anomaly is discussed in
      detail. Compression of the left renal vein between the abdominal aorta and the
      superior mesenteric artery usually induces left renal vein hypertension,
      resulting in varicocele. We propose that the arching of left testicular artery
      over the left renal vein could be an additional possible cause of the left renal
      vein compression. Therefore, knowledge of the possible existence of arching
      gonadal vessels in relation to the renal vein could be of paramount importance to
      vascular surgeons and urologists during surgery in the retroperitoneal region.

PMID- 18043831
TI  - Twin reverse arterial perfusion sequence.
AB  - Twin reverse arterial perfusion sequence occurs in approximately one percent of
      monochorionic twins. This condition is always fatal for the recipient twin and
      carries a high mortality rate for the pump twin. Various treatment options are
      described, but management is continually evolving with the publication of new
      data. We report an acardiac acephalic monochorionic twin who was diagnosed at 31
      weeks gestation. Serial ultrasonographical examinations of the normal pump twin
      showed intrauterine growth restriction but with no evidence of heart failure. A
      healthy pump twin was delivered by caesarean section at 34 weeks.

PMID- 18043832
TI  - Duplicate publication: a joint statement from the Singapore Medical Journal and
      the Medical Journal of Malaysia.

PMID- 18043833
TI  - Physician leadership.
AB  - Doctors, because of the nature of their training and their profession, have to be
      leaders. Subsequently, when they specialise, leadership qualities are even more
      important if they are to be effective in leading the specialty team. It is common
      knowledge that doctors have become leaders in various sectors of society. One of
      the fundamental advantages a doctor has over others in leadership positions is
      his basic training in studying and understanding human nature. With years of
      practice and experience, the doctor, a student of human nature, has a good grasp
      of human behaviour which enables him to become a better leader. The six universal
      and timeless characteristics of great leaders are: ability to share a vision,
      surrounding oneself with great people, ability to coach other team members,
      ability to focus on perfection, developing emotional intelligence and ability to
      train effective leaders. I would like to see three essential qualities in a
      strong leader: ability to secure an "envisioned future", ability to sacrifice in
      order to cultivate loyalty, and courage to do the right thing and protect his
      people. An effective leader positions himself in a situation to ensure survival.
      Having secured the leadership position, one must take certain steps to strengthen
      one's leadership so that it will survive. Six strategies from the Art of War by
      Sun Tzu which are of great practical value are: walk the ground, have trusted
      lieutenants, information gathering, confuse the enemy, win most while doing
      nothing, and that which is too good will not last forever. Sometimes we have to
      change in order to survive. We need to get rid of outmoded practices and shed old
      burdens to take advantage of the present. The task of exiting from leadership is
      facilitated if one has groomed a successor. The longer one is in a leadership
      position, the more difficult it is for one to step down. Some organisations
      retain old leaders as advisors or mentors. They should be just seen and not heard
      and go about their work quietly, contributing to the department. A retired leader
      should be able to command respect from his peers and preserve his dignity.

PMID- 18043834
TI  - Non-surgical interventions for threatened and recurrent miscarriages.
AB  - Many surgical and non-surgical interventions are used in the management of
      threatened and recurrent miscarriages. Evidence-based management of recurrent
      miscarriages requires investigations into the underlying aetiology. When a
      specific cause is identified, directed treatment may reduce miscarriage rates.
      Combined aspirin and heparin for antiphospholipid syndrome, and screening and
      treatment of bacterial vaginosis between ten and 22 weeks of pregnancy with
      clindamycin, are the only interventions proven to be useful in randomised
      controlled trials (RCTs). The use of periconceptional metformin for polycystic
      ovarian (PCO) syndrome is promising, though data from RCTs are still required.
      The use of heparin in inherited thrombophilias, bromocriptine in
      hyperprolactinaemia and luteinising hormone suppression in fertile patients with
      PCO syndrome are more controversial. In threatened miscarriages, or when no cause
      is found, treatment becomes empirical. Supportive care may reduce miscarriage
      rates. Dydrogesterone, a progesterone derivative, may further reduce miscarriage
      rates. Bed rest and avoidance of sexual intercourse, though commonly advised, are
      of no proven benefit. Use of uterine relaxing agents, human chorionic
      gonadotrophin, immunotherapy and vitamins remain controversial in idiopathic
      recurrent miscarriages.

PMID- 18043835
TI  - Educational inequalities associated with health-related behaviours in the adult
      population of Singapore.
AB  - INTRODUCTION: Socioeconomic differences in health-related behaviours have been
      widely studied in the Western populations, but are seldom considered in Asian
      populations. We examined the effect of education attainment on health-related
      behaviours (physical activity, cigarette smoking and alcohol consumption) among
      non-institutionalised Singaporeans aged 18-69 years. METHODS: We used data from
      the Singapore National Health Survey 2004. Information on physical activity,
      cigarette smoking, alcohol consumption and sociodemographic characteristics was
      collected from 4,084 adults. Age-adjusted prevalence of the three health-related
      behaviours by educational attainment was calculated by the direct method.
      Logistic regression models, adjusted for age, gender, ethnic group and employment
      status, were used to estimate the odds ratio and 95% confidence interval, in
      order to study the prevalence of health-related behaviours according to
      educational attainment. RESULTS: The prevalence of physical inactivity, daily
      smoking and regular alcohol consumption was found to be consistently highest
      among men and women with the least education. Prevalence of physical inactivity
      and smoking was inversely related to educational attainment for both genders.
      However, no clear gradient was found between education and alcohol consumption
      for men and women. CONCLUSION: Less-educated Singaporeans were more likely to
      smoke daily, drink alcohol regularly or not to exercise regularly. Health
      promotion policies or programmes aimed at encouraging healthy lifestyles in the
      Singapore population should take into account the educational inequalities in
      these health-related behaviours.

PMID- 18043836
TI  - Emotional and behavioural problems in Singaporean children based on parent,
      teacher and child reports.
AB  - INTRODUCTION: This study aims to determine the prevalence of emotional and
      behavioural problems in a community sample of Singaporean children aged 6-12
      years, and its agreement according to parent, teacher and child reports. METHODS:
      The Child Behaviour Checklist (CBCL), Teacher Rating Form (TRF) and child report
      questionnaires for depression and anxiety were administered to a community sample
      of primary school children. 60 percent of the children sampled (n = 2,139) agreed
      to participate. Parents of a sub-sample of 203 children underwent a structured
      clinical interview. RESULTS: Higher prevalence of emotional and behavioural
      problems was identified by CBCL (12.5 percent) than by TRF (2.5 percent).
      According to parent reports, higher rates of internalising problems (12.2
      percent) compared to externalising problems (4.9 percent), were found. Parent
      teacher agreement was higher for externalising problems than for internalising
      problems. Correlations between child-reported depression and anxiety, and parent
      and teacher reports were low to moderate, but were better for parent reports than
      for teacher reports. CONCLUSION: The prevalence rates of emotional and
      behavioural problems in Singaporean children based on CBCL ratings are comparable
      to those in the West, but the low response rate and exclusion of children with
      special needs limit the generalisability of our findings. Singaporean children
      have higher rates of internalising problems compared to externalising problems,
      while Western children have higher rates of externalising problems compared to
      internalising problems.

PMID- 18043837
TI  - Recall of discharge advice given to patients with minor head injury presenting to
      a Singapore emergency department.
AB  - INTRODUCTION: Most patients presenting to the emergency department (ED) with
      minor head injury (HI) can be discharged, provided a caregiver is present and
      careful discharge instructions are given. The study ED uses an advice leaflet
      with verbal reinforcement to patients and caregivers detailing post-discharge
      instructions and warning symptoms of worsening HI. We aim to evaluate local
      patients' and caregivers' compliance to discharge instructions and their ability
      to recall HI advice. METHODS: A prospective study was conducted in an adult ED
      between April 10, 2006 and May 1, 2006. All patients with minor HI discharged
      from the ED or its 24-hour observation ward were included in the study. A
      telephone survey was conducted within 48 hours of discharge using a standardised
      questionnaire. RESULTS: During the study period, 292 patients had HI, of which
      182 were eligible for the study. 71 were uncontactable and one refused to
      participate, leaving 110 patients in the study. Patients' age ranged between 7
      and 109 years (median 41 years). 100 confirmed receiving HI advice (57 percent
      received by patients, 26 percent caregivers, 16 percent both patients and
      caregivers). 29 percent of respondents reported non-compliance to discharge
      advice. Mean HI-symptom recall score was 1.9 (SD 1.6) (total 9 symptoms). 30
      percent cited other symptoms not part of the HI advice, which they believed
      necessitated a return to the ED. Recall scores were not statistically different,
      regardless of mode of instruction (verbal or printed) or the recipient (patient,
      caregiver or both). CONCLUSION: Our study raises concerns about the reliability
      of discharge advice for minor HI patients.

PMID- 18043838
TI  - Metabolic syndrome in the Hong Kong community: the United Christian Nethersole
      Community Health Service primary healthcare programme 2001-2002.
AB  - INTRODUCTION: With recognition of the important role of central obesity in
      metabolic syndrome (MES), the International Diabetes Federation (IDF) has
      proposed a revised definition for MES in early 2005. Information of MES in
      Chinese by IDF criteria is limited. METHODS: This was a cross-sectional
      observation survey. A sample of 7,473 subjects (2,660 men and 4,813 women) was
      examined. They presented voluntarily in the period between August 2001 and
      September 2002 for health assessment at the three health centres of the United
      Christian Nethersole Community Health Service. RESULTS: The mean age and standard
      deviation was 50.4 +/- 10.6 years (range 19-93 years, median 48.0 years). Among
      them, 30 percent had central obesity, 34 percent had low high-density lipoprotein
      cholesterol, 20 percent had hypertriglyceridaemia, 47 percent had high blood
      pressure, and 23 percent had dysglycaemia. The age-standardised percentages of
      MES by National Cholesterol Education Programme and IDF criteria were 18.3 and
      13.9 percent, respectively. CONCLUSION: MES is not uncommon among the Hong Kong
      Chinese community. Further studies on the management and prevention of MES are
      indicated.

PMID- 18043839
TI  - Inadequate dietary calcium intake in elderly patients with hip fractures.
AB  - INTRODUCTION: Calcium supplementation and pharmacotherapy are recommended in the
      preventive management of osteoporosis. Many previous studies report of
      underdiagnosis and undertreatment of osteoporosis among elderly patients with hip
      fractures. We undertook this study to determine the dietary calcium levels in our
      local elderly population who were admitted with hip fractures. METHODS: 77
      patients, between the ages of 60 and 98 years of age, and admitted to our
      department between January 2001 and September 2001 for hip fractures, were
      studied. The dietary calcium intakes of these patients were determined by a food
      frequency questionnaire and a detailed diet history. Bone mineral density (BMD)
      studies were performed on 55 of these patients to confirm the diagnosis of
      osteoporosis. RESULTS: The mean daily calcium intake was found to be 650 mg. Only
      six of our hip fracture patients (7.8 percent) had a daily calcium intake above
      the recommended levels of 1,000 mg per day. For the 55 patients who had BMD
      performed, only one patient had a BMD within the normal range. 34 patients (64.2
      percent) had hip T-scores in the osteoporotic range and 18 patients (33.9
      percent) had hip T-scores in the osteopenic range. We found that the patients
      with BMD in the osteoporotic and osteopenic ranges had no significant difference
      in the dietary calcium intake. CONCLUSION: The dietary calcium intake of our
      elderly patients with hip fractures is insufficient. They would benefit from
      dietary education and calcium supplements to prevent deterioration in bone
      density and subsequent osteoporotic fractures.

PMID- 18043840
TI  - Clinical features and outcome of emergency percutaneous intervention of left main
      coronary artery occlusion in acute myocardial infarction.
AB  - INTRODUCTION: Acute myocardial infarction (AMI) due to left main coronary artery
      (LMCA) occlusion carries a grave prognosis. Large series reporting on the outcome
      of emergency revascularisation (percutaneous or surgical) of acute LMCA occlusion
      have been scarce. We seek to identify, in our local population, the clinical
      presentation and outcome of this group of patients. METHODS: From January 2000 to
      December 2005, a total of 1,539 patients underwent primary percutaneous coronary
      angioplasty for AMI in our institution. 11 patients (0.8 percent) underwent
      percutaneous intervention to the LMCA. These patients became the subjects of our
      study. Data on demography, clinical features and outcome was collected from all
      in-hospital and clinical notes. One sub-investigator, who was blinded to the
      study outcome, assessed the angiographical features. RESULTS: The overall
      inpatient mortality was 82 percent (9 out of 11). Nine out of 11 patients
      presented with cardiogenic shock. All patients presented with shock died during
      the hospital stay. All patients required intra-aortic balloon counter pulsation
      insertion. Of the two patients who survived till discharge, one had angioplasty
      followed by bypass surgery. The remaining one had angioplasty and stenting to the
      left main artery. Both survivors have been doing well without further major
      adverse cardiac event after an average of 64 months of follow-up. CONCLUSION:
      Percutaneous revascularisation of acute LMCA occlusion is feasible and the best
      outcome is seen in stable patients. Prognosis is still poor in patients with
      unfavourable clinical features.

PMID- 18043841
TI  - Clinical usefulness of per-rectal portal scintigraphy by Tc-99m pertechnetate in
      evaluation of the severity of portal hypertension in cirrhotic patients.
AB  - INTRODUCTION: Variceal haemorrhage is a potentially life-threatening complication
      in cirrhotic patients. Identification of patients at high risk for bleeding is
      particularly important. The aim of this study was to determine the clinical
      usefulness of per-rectal portal scintigraphy (PPS) in the evaluation of the
      severity of portal hypertension in cirrhotic patients, in terms of correlation
      between cirrhosis and the parameters of hepatic functional reserve, and
      identifying the difference of the portal shunt index (PSI) of the bleeding
      oesophageal variceal (BEV) patients and non-BEV patients. METHODS: Portal
      circulations in 67 patients with cirrhosis and oesophageal varices were evaluated
      by Tc-99m pertechnetate PPS. Tc-99m pertechnetate (550 MBq) was instilled into
      the upper rectum, and dynamic images of upper abdomen were taken. Radioactivity
      curves for the liver and the heart were generated sequentially. Through the
      analysis of these curves, the PSI was determined. RESULTS: The results, expressed
      as PSI, were: 11.4 +/- 98.4 percent (mean 66.8) in all 67 cirrhotic patients,
      56.4 +/- 27.1 percent in cirrhotic patients without history of BEV, and 74.9 +/-
      13.6 percent in cirrhotic patients with history of BEV. The PSI was significantly
      lower in cirrhotic patients without BEV than those with BEV (p-value equals
      0.001). The PSI calculated with this method was correlated with the serum
      albumin, the serum bilirubin, the prothrombin time, and the Child-Turcotte-Pugh
      score. CONCLUSION: Tc-99m pertechnetate PPS has clinical usefulness as a
      noninvasive method of choice for quantitatively evaluating the severity of portal
      hypertension in cirrhotic patients.

PMID- 18043842
TI  - Comparison of the results of open carpal tunnel release and KnifeLight carpal
      tunnel release.
AB  - INTRODUCTION: The study compares the results of open release of carpal tunnel
      syndrome with a release done with a proprietary instrument, the KnifeLight, which
      uses a minimal access approach. METHODS: A retrospective study was conducted on
      two groups of patients operated on by the same surgeon between January 1998 and
      August 2002. All cases presented with numbness of six months duration or more,
      and a positive Phalen's test. Open carpal tunnel release was done in the first
      group of 26 consecutive patients before the KnifeLight was introduced in January
      2000. The KnifeLight technique was used in a second consecutive group of 49
      patients. In two patients, the KnifeLight procedure was abandoned because the
      median nerve could not be safely separated from the transverse carpal ligament.
      RESULTS: The two groups were shown to be comparable with respect to clinical
      presentation and nerve conduction studies. There was no complication in both
      groups. However, no advantage could be demonstrated in the use of the KnifeLight
      procedure as compared to the open procedure in respect to improvement in pain,
      numbness or patient satisfaction. The study also showed that the severity of
      nerve conduction changes is not related to the severity of numbness. It is also
      not a good guide to the improvement of numbness and patient satisfaction after
      the operation. CONCLUSION: The method was found to be acceptable to patients as
      an office procedure. The cost of doing either procedure is reduced when done as
      an office procedure, but there is a cost incurred in the use of the KnifeLight
      instrument.

PMID- 18043843
TI  - Cryoglobulinaemia in hepatitis C-positive patients in Iran.
AB  - INTRODUCTION: Cryoglobulins are found in a wide spectrum of disorders but are
      often transient and without clinical implications. The so-called essential mixed
      cryoglobulinaemia shows a striking association with hepatitis C virus (HCV)
      infection (greater than 90 percent). Type II cryoglobulinaemia is the major
      extrahepatic manifestation of HCV infection. This study aims to investigate the
      frequency of cryoglobulinaemia in HCV-positive patients in central Iran. METHODS:
      50 HCV-positive patients referred to the Shaheed Sadoughi Hospital in Yazd, Iran
      from May 2004 to December 2005, were included in the study. Their sera were
      assessed for cryoglobulins. The sera were separated by centrifugation at 37
      degrees Celsius and placed in a four degrees Celsius refrigerator in two tubes,
      one simple and the other, a Wintrobe tube, to see if precipitation occurs during
      a 48-hour up to a seven-day period. RESULTS: In this study, 50 HCV positive
      patients were evaluated. Only two patients were female. Mean age was 32 years
      (ranging from 17 to 52 years). In eight patients, the cryoglobulin test was
      positive. In seven patients, the test became positive less than 72 hours after
      sampling. Only one patient who was positive for cryoglobulinaemia, had clinical
      manifestation of frank vasculitis. CONCLUSION: The prevalence of
      cryoglobulinaemia in Iran may be lower than other areas, and it may be due to a
      higher prevalence of cryoglobulinaemia in females and lower prevalence of
      cryoglobulinaemia in HCV genotype-1a. Most of the cases in our study were male
      and the more prevalent genotype in Iran is genotype-1a.

PMID- 18043844
TI  - Male infertility: polymerase chain reaction-based deletion mapping of genes on
      the human chromosome.
AB  - INTRODUCTION: Y chromosome microdeletions are common in about 10-15 percent of
      men with azoospermia or severe oligospermia. These microdeletions are too small
      to be detected by karyotyping. They can be easily identified using polymerase
      chain reaction (PCR). Most of the microdeletions that cause azoospermia or
      oligospermia occur in the non-overlapping regions of the long arm of the Y
      chromosome. These regions, also called azoospermia factor regions (AZF), are
      responsible for spermatogenesis. The loci are termed AZFa, AZFb and AZFc from
      proximal to distal Yq. Several genes located in AZF regions for spermatogenesis
      is viewed as "AZF candidate genes". This study aims at PCR-based rapid analysis
      of Y chromosome microdeletion, which is a cause for male infertility. METHODS:
      PCR amplification using Y-specific STS (sequence tagged sites) of AZF regions for
      AZFa: DBY and sY84, AZFb: RBM1 and sY127, and AZFc: BPY2 and sY254, were
      conducted. RESULTS: Of the 30 infertile men, 17 were azoospermic and 13 were
      severely oligospermic. Severe oligospermia was diagnosed in those patients who
      produced only one-third the concentrations of the sperm of that found in fertile
      men. Four patients showed a deletion of one or more STS. Two patients had
      complete deletion of AZFc loci, three patients had complete deletion of AZFa loci
      and two patients had complete deletion of AZFb loci. CONCLUSION: The frequency
      involving the microdeletion in the AZF region was found in four out of 30
      azoospermic and severely oligospermic infertile men, i.e. 13.3 percent of the
      total deletions.

PMID- 18043845
TI  - The relative position of the greater palatine foramen in dry Indian skulls.
AB  - INTRODUCTION: We evaluated the relative position of the greater palatine foramen
      (GPF) for precise injection of local anaesthetics, for optimal pain control in
      maxillofacial and dental surgeries. METHODS: The study was conducted in 132 adult
      dried unsexed skulls of the west coast region of Southern India. All the skulls
      studied were normal with fully erupted third molars and free from any
      pathological changes. RESULTS: The statistical analysis indicated there was no
      significant difference in the measurement between the right and left sides with
      regard to the distance of GPF to the midline, GPF to the incisive fossa, GPF to
      the posterior border of the hard palate. The angle made by the line joining the
      GPF to the incisive foramen with the palatal midline (GIM angle) on two sides
      showed statistical significance. The mean angle on the left side was 21.2 +/- 4.2
      degrees and 20.1 +/- 4.2 degrees on the right side. In 74.6 percent of skulls,
      the GPF was located opposite the third maxillary molars, whereas 24.2 percent
      showed the GPF between the second and third molars. In 0.4 percent of skulls, the
      GPF was opposite to the second molar and in 0.8 percent of skulls, the GPF was
      situated beyond the third molar. 46.2 percent of the GPF was directed forward and
      medially, whereas 41.3 percent was directed forward, and 12.5 percent as directed
      forward and laterally. CONCLUSION: The perpendicular distance of the GPF in
      Indian skulls was about 15 mm, the distance of GPF to incisive fossa was
      approximately 37 mm, and the GIM angle was 21 degrees.

PMID- 18043846
TI  - A case of scurvy in Singapore in the year 2006.
AB  - Scurvy is an ancient disease. Over the years, with advances in the understanding
      of the disease, general improvement in health standards and nutrition, scurvy is
      now rarely encountered. The few cases of scurvy reported in the 21st century
      mainly occurred in the neglected elderly, alcoholics and food faddist. We
      describe scurvy due to food selection in a 37-year-old woman with underlying
      eating and obsessive-compulsive disorders. With vitamin C replacement,
      psychiatric medication and cognitive behavioural therapy, there was a dramatic
      improvement in her condition. This case serves as a reminder to the clinician
      that, even though rare in today's practice, ascorbic acid deficiency is still
      encountered, and when recognised, is an easily treatable disease.

PMID- 18043847
TI  - A variation of the phrenic nerve: case report and review.
AB  - During routine dissection in the department of anatomy, the following anatomical
      variations of the phrenic nerve were observed on the right side of the neck of a
      30-year-old male cadaver. The phrenic nerve, in its early course close to its
      origin, gave a communicating branch to the C5 root of the brachial plexus. At the
      level of the root of neck just before entering the thorax, the phrenic nerve was
      located anterior to the subclavian vein. This unique case of phrenic nerve
      variation gains tremendous importance in the context of subclavian vein
      cannulation, implanted venous access portals, and supraclavicular nerve block for
      regional anaesthesia.

PMID- 18043848
TI  - Management of pyogenic liver abscesses - percutaneous or open drainage?
AB  - This pictorial essay aims to review the literature on the management of pyogenic
      liver abscess, focusing on the choice of drainage. Articles on the treatment of
      pyogenic liver abscess, accessed through a MEDLINE search using PubMed, were
      reviewed. A case series of the authors' experience with clinicopathological
      correlation is presented to highlight the indication and outcome of each modality
      of drainage. Intravenous antibiotic is the first line, and mainstay, of
      treatment. Drainage is necessary for large abscesses, equal to or larger than 5
      cm in size, to facilitate resolution. While percutaneous drainage is appropriate
      as first-line surgical treatment in most cases, open surgical drainage is prudent
      in cases of rupture, multiloculation, associated biliary or intra-abdominal
      pathology. Percutaneous drainage may help to optimise clinical condition prior to
      surgery. Laparoscopic drainage is a feasible surgical option with promising
      results in the future. Liver resection is reserved for concomitant localised
      intrahepatic disease and tumour, after control of sepsis. The final verdict on
      the outcome of percutaneous versus open surgical drainage of pyogenic liver
      abscesses requires further studies in a controlled trial setting. Nevertheless,
      in current good clinical practices, the choice of therapy needs to be
      individualised according to patient's clinical status and abscess factors. They
      are complementary in the management of liver abscesses.

PMID- 18043854
TI  - Skeletal differences in bone mineral area and content before and after cure of
      endogenous Cushing's syndrome.
AB  - We examined bone densitometric data in a four-year follow-up period before and
      after the cure of CS. Plasma cortisol concentrations were similar, but the
      duration of estimated glucocorticoid excess was longer in patients with prevalent
      bone fractures compared to those without fractures. After therapy of CS, bone
      area, BMC and BMD increased significantly at the LS and femur during follow-up,
      but they decreased at the forearm, suggesting redistribution of bone minerals
      from the peripheral to the axial skeleton. INTRODUCTION: Only a few studies
      report the changes in bone mineral density (BMD) after the cure of Cushing's
      syndrome (CS). METHODS: Forty-one patients with Cushing's disease, 21 patients
      with adrenal CS and 6 patients with ectopic CS were prospectively enrolled. BMD,
      bone mineral content (BMC) and bone area were measured by DXA. RESULTS: No
      significant correlations were found between serum cortisol concentrations and
      baseline bone densitometric data. After successful therapy of CS, bone area and
      BMD increased significantly at the lumbar spine (LS) and femur during follow-up,
      but they decreased at the forearm. The progressive increase in BMC at the LS had
      a significant negative correlation with the change of the BMC of radius in the
      first and second follow-up years. The change in the body mass index was an
      independent predictor for changes in BMC both at the LS and at the forearm at the
      second year of remission. CONCLUSIONS: The regional differences and the time
      dependent changes of BMC suggest that the source of marked increase in axial BMC
      after the cure of CS is, at least partly, due to the redistribution of bone
      minerals from the peripheral to the axial skeleton.

PMID- 18043855
TI  - Evolutionary analysis of the TPP-dependent enzyme family.
AB  - The evolutionary relationships of the thiamine pyrophosphate (TPP)-dependent
      family of enzymes was investigated by generation of a neighbor joining
      phylogenetic tree using sequences from the conserved pyrophosphate (PP) and
      pyrimidine (Pyr) binding domains of 17 TPP-dependent enzymes. This represents the
      most comprehensive analysis of TPP-dependent enzyme evolution to date. The
      phylogeny was shown to be robust by comparison with maximum likelihood trees
      generated for each individual enzyme and also broadly confirms the evolutionary
      history proposed recently from structural comparisons alone (Duggleby 2006). The
      phylogeny is most parsimonious with the TPP enzymes having arisen from a
      homotetramer which subsequently diverged into an alpha(2)beta(2) heterotetramer.
      The relationship between the PP- and Pyr-domains and the recruitment of
      additional protein domains was examined using the transketolase C-terminal (TKC)
      domain as an example. This domain has been recruited by several members of the
      family and yet forms no part of the active site and has unknown function. Removal
      of the TKC-domain was found to increase activity toward beta-hydroxypyruvate and
      glycolaldehyde. Further truncations of the Pyr-domain yielded several variants
      with retained activity. This suggests that the influence of TKC-domain
      recruitment on the evolution of the mechanism and specificity of transketolase
      (TK) has been minor, and that the smallest functioning unit of TK comprises the
      PP- and Pyr-domains, whose evolutionary histories extend to all TPP-dependent
      enzymes.

PMID- 18043856
TI  - Morphological studies of pulmonary arteriovenous shunting in a lamb model of
      superior cavopulmonary anastomosis.
AB  - We sought to identify and characterize the abnormal vascular structures
      responsible for pulmonary arteriovenous shunting following the Glenn
      cavopulmonary shunt. Superior cavopulmonary shunt is commonly performed as part
      of the staged pathway to total cavopulmonary shunt to treat univentricular forms
      of congenital heart disease, however, clinically significant pulmonary
      arteriovenous malformations develop in some patients after the procedure. The
      causes of pulmonary arteriovenous malformations and other pulmonary vascular
      changes that occur after cavopulmonary shunt are not known. Using a juvenile lamb
      model of superior cavopulmonary anastomosis that reliably produces pulmonary
      arteriovenous malformations, we performed echocardiography and morphological
      analyses to determine the anatomic site of shunting and to identify the vascular
      structures involved. Pulmonary arteriovenous shunting was identified by contrast
      echocardiography in all surviving animals (n = 40) following superior
      cavopulmonary anastomosis. Pulmonary vascular corrosion casts revealed abnormal
      tortuous vessels joining pulmonary arteries and veins in cavopulmonary shunt
      animals but not control animals. In conclusion, unusual channels that bridged
      pulmonary arteries and veins were identified. These may represent the vascular
      structures responsible for arteriovenous shunting following the classic Glenn
      cavopulmonary shunt. Detailed analysis of these structures may elucidate factors
      responsible for their development.

PMID- 18043857
TI  - Magnetic resonance imaging for endomyocardial fibrosis.
AB  - Magnetic resonance images (MRI) of a pediatric patient with endomyocardial
      fibrosis secondary to idiopathic hypereosinophilic syndrome are presented.
      Previously reported in adults, MRI findings of endomyocardial fibrosis in this
      case include right ventricular diastolic dysfunction, mild systolic dysfunction
      and extensive subendocardial delayed contrast enhancement. Right atrial
      enlargement and organized right ventricular thrombus are also demonstrated.

PMID- 18043858
TI  - D-transposition of the great arteries in a case of microduplication 22q11.2.
AB  - The 22q11.2 deletion syndrome is one of the most frequent genetic syndromes,
      mainly characterized by cleft palate, facial dysmorphism, conotruncal heart
      malformations and immune deficiencies. Microduplication of the 22q11.2 region is
      a quite recently characterized genetic entity comprising a variable phenotype
      including some overlapping features with the 22q11.2 deletion syndrome. So far
      only few reports of patients with this microduplication and heart defects have
      been published. To our knowledge this is the first description of a patient with
      genetically confirmed duplication of the 22q11.2 region and d-transposition of
      the great arteries (d-TGA) as well as Ebstein's anomaly.

PMID- 18043859
TI  - Acute coronary artery dilation due to Kawasaki disease and subsequent late
      calcification as detected by electron beam computed tomography.
AB  - We wanted to clarify the relationships between the degree of acute coronary
      artery dilation caused by Kawasaki disease and subsequent late calcification.
      Electron beam computed tomography (EBCT) was used to study 79 patients who had
      previously undergone selective coronary angiograms less than 100 days after the
      onset of Kawasaki disease. The EBCT was performed using an Imatron C-150 with a
      100-ms exposure time and consecutive images at 6-mm intervals. The interval from
      the onset of Kawasaki disease to EBCT ranged from 2 to 242 months (median, 103
      months). The maximum diameters of the right coronary, the left anterior
      descending, and the left circumflex arteries, as well as the bifurcation of the
      left coronary artery were measured in the initial coronary angiograms. A total of
      250 branches, including 53 left coronary arteries, were measured, and the
      relationship between the degree of the initial coronary artery dilation and
      subsequent calcification in the branches and left coronary artery was analyzed.
      The coronary arterial diameter of all branches that eventually calcified was 6 mm
      or greater. The incidence of calcification in branches measuring 6 mm or greater
      on the initial coronary angiogram was 12% at 5 years, 44% at 10 years, and 94% at
      20 years (n = 141). Dilation greater than 6 mm is associated with a high
      probability of late calcification.

PMID- 18043861
TI  - A new selective pre-column ninhydrin-based derivatization for a RP-HPLC
      determination of plasma asymmetric dimethyl-L-arginine (ADMA) by fluorescence
      detection.
AB  - We report a new selective and direct pre-column ninhydrin-based derivatization
      reaction for determination of plasma ADMA levels. This original derivatization
      procedure matched to a validated and rapid RP-HPLC method can be a useful
      alternative to other assays in which time consuming and expensive extraction
      and/or purification steps are required.

PMID- 18043860
TI  - Balloon angioplasty for native aortic coarctation in different anatomic variants.
AB  - Balloon angioplasty for native coarctation of the aorta in infants and children
      is gaining acceptance as an alternative to surgery in discrete membranous
      obstruction. The aim of this study was to assess the immediate and intermediate
      term effectiveness and safety of balloon angioplasty in infants and children with
      discrete membranous obstruction and mild complex arch anomalies. We performed a
      retrospective study evaluating the immediate and intermediate-term results of
      balloon angioplasty in 46 consecutive patients with native coarctation of the
      aorta done between March 1998 and June 2003. Isolated discrete fibromembranous
      obstruction occurred in 32 patients, and 14 patients had mild complex arch
      anomalies. Follow-up was obtained in 40 patients. There was no early mortality.
      The procedure was initially successful in 43 patients (93%). There were three
      immediate failures. Of the 40 patients who were followed, 32 (80%) had maintained
      a cuff pressure gradient of 20 mmHg across the dilated area. Four patients
      developed restenosis, which was successfully treated by repeated balloon
      angioplasty. The other four patients continued to have mild gradient (20-22 mmHg)
      with systolic hypertension and without angiographic evidence of restenosis but
      with isthmus hypoplasia; they received atenolol and captopril. Serial
      echocardiographic measurement of left ventricular dimension and function revealed
      significant improvement after balloon angioplasty of aortic coarctation in
      patients with the echocardiographic picture of hypertensive cardiomyopathy.
      Balloon angioplasty may be considered as a tool in the armamentarium of
      management of aortic coarctation in different anatomic variants, taking into
      consideration the clinical presentation and patient age.

PMID- 18043862
TI  - CHROMSCAN: genome-wide association using a linkage disequilibrium map.
AB  - CHROMSCAN implements a composite likelihood model for the analysis of association
      data. Disease-gene localisation is on a linkage disequilibrium unit (LDU) map,
      and locations and standard errors, for putatively causal polymorphisms, are
      determined by the programme. Distortions of the probability distribution created
      by auto-correlation are avoided by implementation of a permutation test. We
      evaluated the relative efficiency of the LDU map by simulating pseudo-phenotypes
      in real genotype samples. We observed that multi-locus mapping on an underlying
      LDU map reduces location error by approximately 46%. Furthermore, there is a
      small, but significant, increase in power of approximately 5%. Effective meta
      analysis across multiple samples, increasingly important to combine evidence from
      genome-wide and other association data, is achieved through the weighted
      combination of location evidence provided by the programme.

PMID- 18043863
TI  - A novel R198H mutation in the glucose-6-phosphate dehydrogenase gene in the
      tribal groups of the Nilgiris in Southern India.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common red cell
      enzymopathy among humans. In India, G6PD Mediterranean, G6PD Orissa, and G6PD
      Kerala-Kalyan are the three common mutations which account almost 90% of G6PD
      deficiency. Here we describe G6PD Coimbra, an unreported variant from India, and
      a novel 593 G --> A mutation in exon 6 with an amino acid change of Arg 198 His,
      among the tribal groups of the Nilgiris in Southern India. Further, this novel
      mutation was structurally characterized and it was found that the mutation is
      located at the end of the coenzyme domain, which may cause enzyme instability.

PMID- 18043864
TI  - HapMap coverage for SNPs in the Japanese population.
AB  - The coverage of human genomic variations is known to substantially affect the
      success of genome-wide association studies. We therefore assessed the SNP
      coverage in the HapMap database for a total of 1,304 subjects from the Japanese
      population by combining resequencing and high-density genotyping approaches.
      First, we resequenced 48 Japanese subjects in 86 genes (572 kb in total), and we
      then genotyped the subset of tag SNPs and also imputed genotypes for all of the
      detected SNPs in an additional panel of 1,256 subjects. Subsequently, we
      genotyped 555,352 tag SNPs selected from the HapMap in 72 Japanese subjects (from
      the panel of 1,256 subjects) and further imputed genotypes for all SNPs currently
      included in the HapMap. Of 738 common genic SNPs (1.3 per kb) that we detected by
      resequencing, 58% had already been genotyped in the HapMap, and 31% were not
      genotyped but had a proxy SNP in the HapMap with a linkage disequilibrium
      coefficient r (2) > or = 0.8, whereas 11% were not represented in the current
      HapMap database. Thus, the HapMap coverage appears to be high although not
      thorough for SNPs in the Japanese population as compared to its coverage reported
      in Caucasians, and this needs to be considered when we interpret association
      results.

PMID- 18043865
TI  - Evaluation of resequencing on number of tag SNPs of 13 atherosclerosis-related
      genes in Thai population.
AB  - In the candidate gene approach, information about the distribution of single
      nucleotide polymorphisms (SNPs) is a crucial requirement for choosing efficient
      markers necessary for a case-control association study. To obtain such
      information, we discovered SNPs in 13 genes related to atherosclerosis by
      resequencing exon-flanking regions of 32 healthy Thai individuals. In total, 194
      polymorphisms were identified, 184 of them SNPs, four insertions, and the rest
      deletions. Fifty-nine of the SNPs were characterized as novel polymorphisms, and
      these accounted for 30% of the identified SNPs. Comparing allele frequency
      distributions of the Thai population with other Asian populations shows similar
      patterns. In contrast, a low correlation pattern (r = 0.521) was found when
      comparing with either Caucasian or African populations. However, some rare
      alleles (rs11574541 and rs10874913) are found in the Thai population but not in
      other Asian populations. Most of the novel SNPs found were located outside the
      haplotype blocks generated by known SNPs in the Thai population. Only 5.77% of
      the novel SNPs lies in these defined haplotype blocks. The selection of haplotype
      tagging SNPs shows that 8 of 13 genes benefited from the ethnic-specific genotype
      information. That is, when at least one novel SNP was present, the tagging SNPs
      chosen were altered. Functional prediction of 16 nonsynonymous SNPs (nsSNPs) by
      three different algorithm tools demonstrated that five nsSNPs possibly alter
      their corresponding protein functions. These results provide necessary
      information for conducting further genetic association studies involving the Thai
      population and demonstrate that resequencing of candidate genes provides more
      complete information for full genetic studies.

PMID- 18043866
TI  - Sympathetic nerve activity restrains reflex vasodilatation in heart failure.
AB  - BACKGROUND: Blunted reflex muscle vasodilatory response during exercise in heart
      failure (HF) patients may be secondary to augmented vasoconstriction. We tested
      the hypothesis that the exaggerated sympathetic nerve activity restrains the
      reflex muscle vasodilatation during exercise in HF patients. METHODS: We studied
      the reflex vasodilatory response (plethysmography) during 3 min static handgrip
      exercise at 30% maximal voluntary contraction in 10 advanced HF patients (45 +/-
      3 year, NYHA Functional Class III/IV) and 10 age-matched normal controls (NC, 40
      +/- 3 year, P = 0.23) during intra-arterial infusion of: (1) saline control; and
      (2) alpha-adrenergic blocker (phentolamine). RESULTS: Baseline forearm vascular
      conductance (FVC) was lower in HF patients than in NC (2.07 +/- 0.2 vs. 4.26 +/-
      0.6 units, respectively; P = 0.002). FVC responses during exercise increased
      significantly in NC, but not in HF patients (delta changes: 1.05 +/- 0.4 vs. 0.05
      +/- 0.2 units, respectively). Phentolamine significantly increased resting FVC in
      HF patients (from 2.07 +/- 0.2 to 5.74 +/- 0.7 units, P = 0.00004) and restored
      reflex vasodilatory responses during exercise (delta changes: from 0.05 +/- 0.2
      to 1.82 +/- 0.9 units) eliminating the difference in FVC between both groups.
      CONCLUSIONS: The blunted reflex muscle vasodilatory response during exercise in
      advanced HF patients is, at least in part, due to the increase in sympathetic
      nerve activity.

PMID- 18043868
TI  - Efficient expression in E. coli of an enantioselective nitrile hydratase from
      Rhodococcus erythropolis.
AB  - The genes encoding an enantioselective nitrile hydratase (NHase) from Rhodococcus
      erythropolis AJ270 have been cloned and an active NHase has been produced in
      Escherichia coli. Maximal activity was found when the genes encoding the alpha-
      and beta-subunits were transcribed as one unit and the gene encoding the P44k
      activator protein as a separate ORF on a single replicon. Addition of n-butyric
      acid and FeSO(4 )could improve NHase activity. Coexpression of the GroEL-GroES
      chaperone proteins increased activity in the absence of P44k protein but had no
      effect in the presence of P44k. The recombinant enzyme was highly
      enantioselective in the synthesis of S-(+)-3-benzoyloxy- 4-cyanobutyramide from
      the prochiral substrate 3-benzoyloxyglutaronitrile.

PMID- 18043867
TI  - Post-transcriptional gene regulation: from genome-wide studies to principles.
AB  - Post-transcriptional regulation of gene expression plays important roles in
      diverse cellular processes such as development, metabolism and cancer
      progression. Whereas many classical studies explored the mechanistics and
      physiological impact on specific mRNA substrates, the recent development of
      genome-wide analysis tools enables the study of post-transcriptional gene
      regulation on a global scale. Importantly, these studies revealed distinct
      programs of RNA regulation, suggesting a complex and versatile post
      transcriptional regulatory network. This network is controlled by specific RNA
      binding proteins and/or non-coding RNAs, which bind to specific sequence or
      structural elements in the RNAs and thereby regulate subsets of mRNAs that partly
      encode functionally related proteins. It will be a future challenge to link the
      spectra of targets for RNA-binding proteins to post-transcriptional regulatory
      programs and to reveal its physiological implications.

PMID- 18043869
TI  - Characterization of secreted recombinant Toxoplasma gondii surface antigen 2
      (SAG2) heterologously expressed by the yeast Pichia pastoris.
AB  - The surface antigen 2 (SAG2) gene of the protozoan parasite, Toxoplasma gondii,
      was cloned and extracellularly expressed in the yeast Pichia pastoris. The
      effectiveness of the secreted recombinant SAG2 (rSAG2-S) as a serodiagnosis
      reagent was assessed by western blots and ELISA. In the western blot assay, rSAG2
      S reacted with all Toxoplasma-antibody positive human serum samples but not with
      Toxoplasma-negative samples. In the ELISA, rSAG2-S yielded sensitivity rates
      ranging from 80% (IgG negative, IgM positive) to 100% (IgG positive, IgM
      negative). In vivo experiments showed that serum from mice immunized with rSAG2-S
      reacted specifically with the native SAG2 of T. gondii. These mice were protected
      when challenged with live cells of T. gondii.

PMID- 18043870
TI  - Entrapment of beta-galactosidase in polyvinylalcohol hydrogel.
AB  - beta-Galactosidase isolated from Aspergillus oryzae was immobilized in lens
      shaped polyvinylalcohol capsules (with activity 25 U g(-1)) giving 32% of its
      original activity. Immobilization did not change the pH optimum (4.5) of lactose
      hydrolysis. The relative enzyme activity during product inhibition testing was,
      in average, 10% higher for immobilized enzyme. No decrease of activity was
      observed after 35 repeated batch runs and during 530 h of continuous hydrolysis
      of lactose (10%, w/v) at 45 degrees C. The immobilized enzyme was stable for 14
      months without any change of activity during the storage at 4 degrees C and pH
      4.5.

PMID- 18043871
TI  - Structure discrimination for the C-terminal domain of Escherichia coli trigger
      factor in solution.
AB  - NMR measurements can give important information on solution structure, without
      the necessity for a full-scale solution structure determination. The C-terminal
      protein binding domain of the ribosome-associated chaperone protein trigger
      factor is composed of non-contiguous parts of the polypeptide chain, with an
      interpolated prolyl isomerase domain. A construct of the C-terminal domain of
      Escherichia coli trigger factor containing residues 113-149 and 247-432, joined
      by a Gly-Ser-Gly-Ser linker, is well folded and gives excellent NMR spectra in
      solution. We have used NMR measurements on this construct, and on a longer
      construct that includes the prolyl isomerase domain, to distinguish between two
      possible structures for the C-terminal domain of trigger factor, and to assess
      the behavior of the trigger factor C-terminal domain in solution. Two X-ray
      crystal structures, of intact trigger factor from E. coli (Ferbitz et al., Nature
      431:590-596, 2004), and of a truncated trigger factor from Vibrio cholerae
      (Ludlam et al., Proc Natl Acad Sci USA 101:13436-13441, 2004) showed significant
      differences in the structure of the C-terminal domain, such that the two
      structures could not be superimposed. We show using NMR chemical shifts and long
      range nuclear Overhauser effects that the secondary and tertiary structure of the
      E. coli C-terminal domain in solution is consistent with the crystal structure of
      the E. coli trigger factor and not with the V. cholerae protein. Given the
      similarity of the amino acid sequences of the E. coli and V. cholerae proteins,
      it appears likely that the structure of the V. cholerae protein has been
      distorted as a result of truncation of a 44-amino acid segment at the C-terminus.
      Analysis of residual dipolar coupling measurements shows that the overall
      topology of the solution structure is completely inconsistent with both
      structures. Dynamics analysis of the C-terminal domain using T1, T2 and
      heteronuclear NOE parameters show that the protein is overall rather flexible.
      These results indicate that the structure of this domain in solution resembles
      the X-ray crystal structure of the E. coli protein in secondary structure and at
      least some tertiary contacts, but that the overall topology differs in solution,
      probably due to structural fluctuation.

PMID- 18043872
TI  - Tumor microenvironment, a dangerous society leading to cancer metastasis. From
      mechanisms to therapy and prevention.
AB  - Cancer is no longer considered by scientists just a jumble of mutated cells. To
      grow, invade and metastasize, a treacherous society between cancer and host cells
      must be formed, and this association provides novel and effective clinical
      targets for cancer control and prevention. This collection of reviews at the
      front-edge of scientific knowledge focuses on host-tumor cell interactions, the
      disastrous consequences they can produce and approaches the ways to break up
      these cellular conspiracies, to leave the tumor cells unattended and vulnerable.

PMID- 18043873
TI  - Recent applications of Kirkwood-Buff theory to biological systems.
AB  - The effect of cosolvents on biomolecular equilibria has traditionally been
      rationalized using simple binding models. More recently, a renewed interest in
      the use of Kirkwood-Buff (KB) theory to analyze solution mixtures has provided
      new information on the effects of osmolytes and denaturants and their
      interactions with biomolecules. Here we review the status of KB theory as applied
      to biological systems. In particular, the existing models of denaturation are
      analyzed in terms of KB theory, and the use of KB theory to interpret computer
      simulation data for these systems is discussed.

PMID- 18043874
TI  - The elderly in the emergency department: a critical review of problems and
      solutions.
AB  - The elderly are an ever increasing population in overcrowded emergency
      departments (EDs) in many countries. They have multiple health problems and
      consume more time and resources than younger patients. They are more frequently
      admitted and experience adverse outcomes after they are discharged from the ED.
      These frail patients could require specific skills, instruments and
      organisational models of emergency care in order to look after their complex
      needs. As such, several approaches have been tried and tested to improve
      emergency care for them. This article analyses the epidemiological load and
      problems faced when confronted with elder ED patients. We critically review
      organisational models, clinical approaches and methodologies in order to reduce
      ED physicians' difficulties and to improve quality of care and outcomes for elder
      patients. Triage, clinical assessment and discharge are identified as critical
      moments during an emergency care process, and interesting and useful instruments
      are proposed as possible solutions.

PMID- 18043875
TI  - Please, sir, pull down your socks!

PMID- 18043879
TI  - [Epidemiologic "paradox"--Why do 'obese' patients have a better prognosis?].

PMID- 18043876
TI  - CD40/CD40L system and vascular disease.
AB  - Several distinct lines of investigation in the context of atherosclerosis dealing
      with low-grade inflammation, oxidative stress and platelet activation are now
      emerging, with CD40/CD40L system as the missing link. CD40 ligand is a
      transmembrane glycoprotein structurally related to tumour necrosis factor-alpha
      and more than 95% of the circulating CD40L derives from platelets. CD40L appears
      as a multiplayer of several cell types in the inflammatory network. The
      peculiarity of CD40L as an inflammatory mediator derived from platelets expands
      the functional repertoire of platelets from players of haemostasis and thrombosis
      to powerful amplifiers of inflammation by promoting the release of cytokines and
      chemokines, cell activation and cell-cell interactions. The multifunctional role
      of CD40L, as a simultaneous activator of all these systems, further blurs the
      intricate relationship between such events both in the physiological systems and
      the pathological derangement occurring in atherothrombosis.

PMID- 18043880
TI  - [Why do obese dialysis patients live longer--a hypothesis].

PMID- 18043881
TI  - Lethal midline granuloma: a case of T-cell lymphoma.

PMID- 18043882
TI  - Prediction of clinical outcome in patients with non-ST-elevation acute coronary
      syndrome (NSTE-ACS) using the TIMI risk score extended by N-terminal pro-brain
      natriuretic peptide levels.
AB  - BACKGROUND: N-terminal pro-brain natriuretic peptide (Nt-proBNP) is a strong
      independent predictor of death in acute coronary syndromes. In order to improve
      risk assessment in patients with unstable coronary artery disease we investigated
      the role of the additional determination of Nt-proBNP levels in patients sub
      grouped into high-, medium- and low-risk groups according to the TIMI risk score.
      METHODS: Nt-proBNP was determined in 145 consecutive patients admitted to our
      clinic with typical anginal pain in the past 24 hours and normal left ventricular
      function. Using classification and regression tree analysis, we investigated
      whether Nt-proBNP levels provide clinically relevant prognostic information in
      addition to the TIMI risk score. Nt-proBNP concentrations were determined using a
      commercially available assay from Biomedica, Austria. The normal range of this
      assay is <2827 pg/ml. RESULTS: Multivariate logistic regression analysis revealed
      that TIMI scores and Nt-proBNP levels are independent predictors of mortality (P
      = 0.001 and P < 0.001, respectively). Patients with Nt-proBNP levels >5225 pg/ml
      had the highest mortality rate, independent of their TIMI risk classification. In
      the subset of patients with Nt-proBNP < or =5225 pg/ml, patients at TIMI medium
      risk but with Nt-proBNP above 2827 pg/ml had significantly higher mortality than
      patients with lower levels of Nt-proBNP (P = 0.03). Accordingly, we developed a
      combined risk score consisting of four risk groups: very high (Nt-proBNP > or
      =5225 pg/ml), high (TIMI high-risk group or TIMI medium-risk group and Nt-proBNP
      >2827 pg/ml), medium (TIMI medium-risk group and Nt-proBNP < or =2827 pg/ml) and
      low (TIMI low-risk group). The area under the receiver operating characteristic
      curve was 0.772 for the TIMI score alone and 0.863 for the combined risk score (P
      < 0.001). CONCLUSION: Determination of plasma Nt-proBNP levels and incorporation
      of these into TIMI risk classification by creating a combined risk score
      significantly improves risk assessment of patients with unstable coronary artery
      disease.

PMID- 18043883
TI  - Abdominal wall pain--classification, diagnosis and treatment suggestions.
AB  - BACKGROUND AND OBJECTIVE: Abdominal pain is generally believed to be a symptom of
      intra-abdominal disease. When no pathological findings are evident, abdominal
      pain is considered functional. Abdominal pain, however, may also originate in the
      abdominal wall. METHODS: Consecutive patients with unexplained abdominal pain
      were enrolled in a prospective observational study in a gastroenterologic clinic
      during a period of three years. The following criteria were tested: Can abdominal
      pain be elicited by physical movement? Is the source of pain localized to a
      circumscribed site in the abdominal wall? Can pain be provoked by digital
      palpation in this area and does pain increase when the abdominal muscles are
      tensed? RESULTS: Clinical examination of 55 patients revealed small painful pits
      in the abdominal wall with varying intensity of pain when the abdominal muscles
      were contracted: in 39 patients the painful area was located in the semilunar
      line, in seven patients the pain originated in the linea alba between xiphoid and
      umbilicus, in five cases the painful spots were situated within the rectus
      muscle, and in four patients the pain was localized along the costal arch. Of the
      39 patients with pain in the semilunar line, 16 had a BMI > 30, 12 presented with
      anxiety and depression, and 10 reported bloating and straining during defecation.
      Pain in the rectus muscle was associated with exercise. The patients with pain in
      the linea alba and at the costal arch suffered from obesity, anxiety or
      depression. CONCLUSIONS: These findings suggest that repeated forceful
      contractions of the abdominal wall muscles during exercise and straining, as well
      as chronic inflation of the abdominal wall by fat pads and by bloating, may cause
      strain and pain in the abdominal wall at sites predestined by anatomy. Symptom
      specific anxiety may be a consequence of chronic unexplained abdominal pain. A
      novel classification of abdominal wall pain is proposed. The correct diagnosis
      will avoid repeated and costly investigations and relieve the patient's anxiety.

PMID- 18043884
TI  - Prevalence and risk factors for osteopenia/osteoporosis in an HIV-infected male
      population.
AB  - The objective of our investigation was to estimate the prevalence of
      osteopenia/osteoporosis in men with HIV/AIDS and evaluate the role of
      antiretroviral treatment (ART), HIV and other risk factors in reducing bone
      mineral density (BMD). All known Slovenian HIV-infected ART-naive and treated
      males (infected or treated > 12 months) were invited to participate in a cross
      sectional study. Data were collected on age, BMI, waist-hip ratio, family history
      of hip fracture, duration of infection, duration of ART, smoking, alcohol,
      exercise, viral load and CD4+ cells. BMD was measured using dual X-ray
      absorptiometry. A total of 96 patients (out of 133 who fulfilled the inclusion
      criteria) were assessed and allocated into three groups: group A (n = 24), ART
      naive; group B1 (n = 37), treated with non-protease-inhibitor (PI) containing
      ART; and group B2 (n = 35), treated with PI-containing ART. The prevalence of
      osteopenia/osteoporosis was 57/96 (59%): osteopenia 45/96 (47%) and osteoporosis
      12/96 (12%). Significantly lower BMD was detected in group A (P = 0.020).
      Multiple logistic regression analysis showed ART to be an independent negative
      predictor for reduced BMD (P = 0.037; OR = 0.29, 95%CI 0.09-0.93). Vitamin D(3)
      deficiency was detected in 79 (82%) of the patients. The study group represented
      72% of the national HIV-infected male population; this proportion being higher
      than in any other study reported to date. The prevalence of reduced BMD was
      notably higher than the national prevalence among men of comparable age. There
      was no association between reduced BMD and any specific ART. According to our
      results, absence of ART was confirmed as an independent predictor of
      osteopenia/osteoporosis. Targeted screening and early treatment present a
      reasonable strategy for preventing reduced BMD in HIV-infected patients, but
      correcting vitamin D(3) levels could also be an important component.

PMID- 18043885
TI  - [Permanent interstitial brachytherapy (seeds) for patients with primary localized
      prostate cancer: analysis of 100 patients].
AB  - INTRODUCTION: The aim of this retrospective study was to evaluate late toxicity
      and biochemical disease-free survival of patients with primary localised prostate
      cancer, who had been treated with permanent seed implantation at the radiotherapy
      department of the Medical University of Vienna. METHODS AND MATERIALS: Between
      08/1999 and 11/2006 100 patients were treated with ultrasound guided
      transperineal seed implantation (94 patients with Iodine and 6 patients with
      Palladium). 53 patients received additional hormone therapy. According to T
      stage, Gleason Score and PSA, patients were divided into three risk groups (low,
      intermediate and high risk). Late gastrointestinal and genitourinary side effects
      and biochemical disease-free survival were evaluated. RESULTS: The patients were
      followed up at a median time of 28 months (3-88 months). The median patient age
      was 67.5 years (47-79 years). The distribution of low, intermediate and high risk
      group patients was 63%, 35% and 2%. The 2-year actuarial rates of late Grade > or
      =2 gastrointestinal and genitourinary side effects were 5% and 65%. The 2-year
      biochemical disease-free survival rate was 88% (all patients), 90% (low risk) and
      88% (intermediate risk), respectively. Multivariate analysis demonstrated T-stage
      (p = 0.03), PSA (p = 0.02) and patient age (p = 0.02) to be significant factors
      influencing biochemical disease-free survival. CONCLUSION: Ultrasound guided
      transperineal seed implantation in patients with low-risk prostate cancer is an
      additional treatment option showing promising results.

PMID- 18043886
TI  - [Evaluation of therapy outcome on a psychiatric admission ward. Background,
      methods and first results of a project on quality management].
AB  - BACKGROUND: Quality management is an important management tool in modern health
      care systems. This applies also to the mental health care system, where in the
      past decade many concepts have been developed on how to implement quality
      management appropriately and successfully. However, for the German speaking
      countries there are only very few studies on the evaluation of therapy outcome in
      psychiatric inpatient populations available, furthermore they deal primarily with
      diagnostic subgroups. The aim of this study was to develop a method to assess the
      quality of therapy on regular psychiatric admission wards. An important aspect
      was to include all diagnostic subgroups of a psychiatric inpatient population.
      METHODS: In an explorative field study and by means of a specially designed
      evaluation method, therapy courses of a psychiatric inpatient population were
      assessed. Indicators of therapy outcome were: psychopathology, level of
      psychosocial functioning, motivation of the patient for therapy, suicide
      attempts, legal status of the patient, patient violence and coercive treatment of
      the patient. The following assessment and rating scales were used: Brief
      Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HAMD), Global
      Assessment of Function (GAF), Social and Occupational Functioning Assessment
      Scale (SOFAS) and the Symptom-Checklist SCL-9. RESULTS: Changes in the courses of
      therapy of a psychiatric inpatient population in all diagnostic subgroups in the
      dimensions psychopathology and level of social functioning could be reproduced
      significantly using BPRS, HAMD and GAF scales. Difference values T(1)-T(2) were
      6.6 +/- 6.9 (p = 0.019) in BPRS, 5.1 +/- 8.1 (p = 0.029) in HAMD and -5.5 +/-
      10.1 (p = 0.028) in GAF. The entire battery of rating scales was successfully
      applied in 32% of all patients (drop out rate: 68%). In the subgroup of immigrant
      patients the entire battery of rating scales could be applied only in 17.4%,
      which accounts for a significantly higher drop out rate (82.6%; p = 0.067).
      DISCUSSION: Using the presented evaluation system therapy outcome and quality of
      therapy are easy to assess. The results of the quality assessment can be used in
      further therapeutic processes.

PMID- 18043887
TI  - [Dr. Rosa Maria Rossler (Wien 1901 - Istanbul 1954): her work in Istanbul and her
      contribution to Turkish medicine].
AB  - During the Turkish University Reform in 1933 the Turkish Government invited many
      foreign scientists in order to assign them to Istanbul University. Almost all of
      them were scientists who had escaped from Hitler's Germany. In 1938, also some
      Austrian scientists who had to leave their country were included into the staff
      of Istanbul University. Dr. Rosa Maria Rossler, born in Vienna in 1901, came to
      Turkey in 1934, earlier than the other Austrians did. She worked in the Institute
      of Pathologic Anatomy of the Medical Faculty of Istanbul University permanently
      from 1937 under Prof. Dr. Philipp Schwartz; after ten years she moved to the
      2(nd) Clinic for Internal Diseases under Prof. Dr. Erich Frank, in the same
      faculty. She participated in training sessions in both departments and translated
      books of both her superiors from German into Turkish. One of the most important
      reform goals of Turkish University was to provide students with modern textbooks.
      Rossler died in 1954, at a young age, in Turkey, where she had lived alone for
      twenty years. The article illustrates the impression she left in Turkish
      medicine.

PMID- 18043888
TI  - Contralateral stroke during carotid endarterectomy due to abnormalities in the
      circle of Willis.
AB  - Approximately 10-20% of patients will not tolerate cross-clamping of the common
      carotid artery for carotid endarterectomy procedures. The most frequent causes of
      neurological deficits are either embolization of particulate matter or cerebral
      hypoperfusion. Insufficient blood flow through primary collaterals of the circle
      of Willis is the main reason for hypoperfusion that requires immediate shunt
      placement. Although excessive preoperative imaging is not indicated in many
      patients undergoing disobliteration of a stenosed internal carotid artery, there
      are some patients with particular anatomic constellations who would benefit from
      a more detailed preoperative work-up. In these cases, the specific risk should be
      evaluated prior to surgery in order to make plans for appropriate intraoperative
      management regarding neurologic monitoring and shunt insertion. As regional
      anesthesia permits early detection of ischemic symptoms, it is advantageous in
      these patients. We report a case where regional anesthesia allowed early
      detection of rapidly progressing signs of bi-hemispheric brain ischemia in a
      patient with diabetes and with at that time unknown severe abnormalities of the
      circle of Willis. Lack of adequate collateralization was detected only after
      surgery, in a combined perfusion-magnetic resonance imaging study. In symptomatic
      diabetics with low-grade stenosis of the internal carotid artery, preoperative
      assessment of the function of the circle of Willis may therefore be helpful in
      predicting any increased risk for intraoperative cerebral ischemia.

PMID- 18043889
TI  - Catheter-related Leuconostoc bacteremia secondary to pulmonary Mycobacterium
      xenopi infection.
AB  - Infection caused by Leuconostoc spp. is very rare. We report a case of
      Leuconostoc bacteremia in a patient receiving antimycobacterial chemotherapy for
      pulmonary Mycobacterium xenopi infection. In addition, the patient presented
      several known characteristic predisposing factors associated with Leuconostoc
      infection, such as severe underlying disease, previous long-term antibiotic
      treatment, indwelling intravascular catheter, prolonged parenteral feeding,
      previous methicillin-resistant Staphylococcus epidermidis (MRSE) bacteremia with
      subsequent vancomycin treatment, and prolonged hospitalization. Leuconostoc spp.
      were isolated from several blood cultures and from a retracted intravascular
      catheter. After removal of the intravascular catheter the patient's condition
      improved without additional antibiotic treatment. To our knowledge, this is the
      first report of a patient with Leuconostoc spp. infection secondary to pulmonary
      non-tuberculous mycobacteriosis.

PMID- 18043890
TI  - Is women scientists' approach to science more interdisciplinary?

PMID- 18043891
TI  - Headspace volatile markers for sensitivity of cocoa (Theobroma cacao L.) somatic
      embryos to cryopreservation.
AB  - The mechanisms that reduce the viability of plant somatic embryos following
      cryopreservation are not known. The objective of the present study was to
      evaluate the sensitivity of cocoa (Theobroma cacao L.) somatic embryos at
      different stages of an encapsulation-dehydration protocol using stress-related
      volatile hydrocarbons as markers of injury and recovery. The plant stress hormone
      ethylene and volatile hydrocarbons derived from hydroxyl radicals (methane) and
      lipid peroxidation (ethane) were determined using gas chromatography headspace
      analysis. Ethylene and methane were the only volatiles detected, with both being
      produced after each step of the cryogenic protocol. Ethylene production was
      significantly reduced following exposure to liquid nitrogen, but then increased
      in parallel with embryo recovery. In contrast, the production of methane was
      cyclic during recovery, with the first cycle occurring earlier for embryos
      recovered from liquid nitrogen and desiccation than those recovered from earlier
      steps in the protocol. These results suggest that loss of somatic embryo
      viability during cryopreservation may be related to the oxidative status of the
      tissue, and its capacity to produce ethylene. This study has demonstrated that
      headspace volatile analysis provides a robust non-destructive analytical approach
      for assessing the survival and recovery of plant somatic embryos following
      cryopreservation.

PMID- 18043892
TI  - Quantitative plaque characterization with coronary CT angiography (CTA): current
      challenges and future application in atherosclerosis trials and clinical risk
      assessment.

PMID- 18043893
TI  - MRI of great vessel morphology and function in Ehlers-Danlos syndrome type IV.
AB  - The purpose of this study was to investigate whether large arteries in subjects
      with Ehlers-Danlos Syndrome Type IV (EDS IV) exhibit altered morphological and
      functional characteristics that might indicate the risk of complications.
      Subjects with EDS IV, an inherited disorder of type III collagen, have a
      significant lifetime risk of arterial rupture. Magnetic Resonance Imaging (MRI)
      of the aorta and carotid artery was used to measure diameter, wall thickness,
      pulse propagation velocity, and spin-spin relaxation time constant (T(2)) of the
      artery walls. These measurements were made and compared by a two-sided t-test in
      17 subjects with EDS IV and in eight age and gender matched sibling controls.
      Additionally, Spearman correlation was computed between measurements and the
      average longevity of affected relatives. Comparing controls to 15 subjects with
      no known prior aortic complications, we found no differences in the diameters of
      the descending thoracic and abdominal aortas, but did find ascending aorta
      dilatation in two subjects (13%). We also found a trend in EDS IV subjects toward
      higher wall thicknesses after normalizing by body surface area for both the
      abdominal aorta (P=0.05) and the common carotid artery (P=0.07). Finally, we
      found a significant negative correlation (R= -0.82, P=0.02) between age-adjusted
      pulse propagation velocity and familial longevity. In conclusion, preliminary
      evidence suggests that elevated pulse propagation velocity, which indicates
      reduced vessel distensibility, may be a risk factor for complications of EDS IV.
      Ascending aorta dilatation and increased vessel wall thickness were also found in
      subjects with EDS IV and represent potential risk factors for future study.

PMID- 18043895
TI  - TGFbeta2 and TbetaRII are valid molecular biomarkers for the antiproliferative
      effects of tamoxifen and tamoxifen metabolites in breast cancer cells.
AB  - Response to treatment with the antiestrogen tamoxifen is variable and at least
      partially due to its highly complex metabolism. Tamoxifen is transformed by
      polymorphic and inducible cytochrome P450 enzymes to a large number of
      metabolites with varying biological activities. The estrogen receptor dependent
      growth inhibitory effect of antiestrogens is mediated by activation of
      antiproliferative Transforming Growth Factor beta (TGFbeta) signal transduction
      pathways. The aim of the present study was to establish if TGFbeta2 or TGFbeta
      receptor II (TbetaRII), could be used as markers to assess the pharmacological
      potency of tamoxifen and its metabolites. Consequently, we analyzed the growth
      inhibitory effect of tamoxifen and its major metabolites and explored whether it
      correlated with their capacity to induce TGFbeta2 and TbetaRII expression. Human
      breast cancer cells (MCF-7 and T47D) were treated with tamoxifen and tamoxifen
      metabolites and mRNA expression of TGFbeta2 and TbetaRII was analyzed by
      quantitative RT-PCR. Only two metabolites 4-hydroxytamoxifen and N-desmethyl-4
      hydroxytamoxifen had significant antiproliferative activity and were able to
      induce TGFbeta2 and TbetaRII. Plasma concentrations of these metabolites are
      usually very low in patients. However, even minor growth inhibitory effects at
      concentrations which are below the limit of quantification in plasma samples
      resulted in clearly discernible effects on expression of TGFbeta2 and TbetaRII.
      Taken together, our data demonstrate that TGFbeta2 and TbetaRII are very specific
      and sensitive biomarkers for the antiestrogenic activity of tamoxifen metabolites
      in breast cancer.

PMID- 18043894
TI  - MRI compared to conventional diagnostic work-up in the detection and evaluation
      of invasive lobular carcinoma of the breast: a review of existing literature.
AB  - PURPOSE: The clinical diagnosis and management of invasive lobular carcinoma
      (ILC) of the breast presents difficulties. Magnetic resonance imaging (MRI) has
      been proposed as the imaging modality of choice for the evaluation of ILC. Small
      studies addressing different aspects of MRI in ILC have been presented but no
      large series to date. To address the usefulness of MRI in the work-up of ILC, we
      performed a review of the currently published literature. MATERIALS AND METHODS:
      We performed a literature search using the query "lobular AND (MRI OR MR OR MRT
      OR magnetic)" in the Cochrane library, PubMed and scholar.google.com, to retrieve
      all articles that dealt with the use of MRI in patients with ILC. We addressed
      sensitivity, morphologic appearance, correlation with pathology, detection of
      additional lesions, and impact of MRI on surgery as different endpoints. Whenever
      possible we performed meta-analysis of the pooled data. RESULTS: Sensitivity is
      93.3% and equal to overall sensitivity of MRI for malignancy in the breast.
      Morphologic appearance is highly heterogeneous and probably heavily influenced by
      interreader variability. Correlation with pathology ranges from 0.81 to 0.97;
      overestimation of lesion size occurs but is rare. In 32% of patients, additional
      ipsilateral lesions are detected and in 7% contralateral lesions are only
      detected by MRI. Consequently, MRI induces change in surgical management in 28.3%
      of cases. CONCLUSION: This analysis indicates MRI to be valuable in the work-up
      of ILC. It provides additional knowledge that cannot be obtained by conventional
      imaging modalities which can be helpful in patient treatment.

PMID- 18043896
TI  - Long-term pattern of disease recurrence among patients with early-stage breast
      cancer according to estrogen receptor status and use of adjuvant tamoxifen.
AB  - PURPOSE: Recent studies on the pattern of gene expression in estrogen receptor
      positive and negative tumours have revealed profound differences according to
      receptor status. However, it remains unclear if these differences reflect
      phenotypic traits in addition to sensitivity to endocrine therapy. This paper
      describes the long-term pattern of disease recurrence among ca. 2,600 pre- and
      post-menopausal patients with primary breast cancer according to estrogen
      receptor status. MATERIAL AND METHODS: The study was based on patients with an
      operable, invasive breast cancer entered in one of three controlled clinical
      trials conducted by the Stockholm Breast Cancer Group. We selected those 2,562
      patients who had been randomly allocated between adjuvant tamoxifen and no
      adjuvant systemic therapy. These patients had a known estrogen receptor status.
      RESULT: Tamoxifen reduced locoregional (8.8% vs. 12.4%, hazard ratio (HR), 0.66;
      95% CI, 0.52-0.83; P = 0.001, distant recurrences (17.2% vs. 20.2%, HR, 0.81; CI,
      0.68-0.97; P = 0.018, as well as breast cancer death (18.7% vs. 23.7%, HR, 0.78;
      CI, 0.67-0.92; P = 0.002). Among patients not allocated to tamoxifen there was no
      significant differences in term of neither locoregional (12.4% vs. 12.4%, HR, 1;
      CI, 0.72-1.41; P = 0.98), nor distant metastases (18.5% vs. 20.7%, HR, 1.11;CI,
      0.85-1.45; P = 0.46) according to ER status. The pattern of metastases was not
      different in ER positive comparison with ER negative. CONCLUSION: The results
      showed that the mentioned substantial differences in terms of gene expression
      appeared mainly to be related to endocrine sensitivity and not to metastatic
      potential. However, a slight advantage during the first five years for the ER
      positive versus ER negative patients in terms of cumulative incidence of events,
      suggested that ER negativity in some cases is correlated with an increased tumour
      growth rate.

PMID- 18043897
TI  - Multicenter phase II trial of neoadjuvant exemestane for postmenopausal patients
      with hormone receptor-positive, operable breast cancer: Saitama Breast Cancer
      Clinical Study Group (SBCCSG-03).
AB  - This multicenter phase II trial evaluated the efficacy and tolerability of 4
      months of neoadjuvant exemestane in 44 postmenopausal patients with estrogen
      receptor (ER)-positive and/or progesterone receptor-positive, stage II to IIIB
      breast cancer measuring >or=3 cm. Pathological response was assessed by a central
      review board using response criteria proposed by the Japanese Breast Cancer
      Society. Clinical response [complete or partial response (PR)] was assessed by
      caliper, mammography, or ultrasound. Rates of breast-conserving surgery (BCS) and
      adverse events were also evaluated. A pathological response was observed in 13
      (43%) of 30 patients who underwent surgery at 4 months. Fourteen patients were
      excluded from the pathological analysis: eight continued exemestane because of PR
      or stable disease (SD) at 4 months, three underwent chemotherapy because of
      progressive disease, and three underwent surgery within 2 months because of
      adverse events. A clinical response was seen in 27 (66%) of 41 evaluable
      patients. BCS was performed in 27 (90%) of 30 patients who underwent surgery at 4
      months. Of the ten patients eligible for mastectomy at baseline, six chose to
      continue exemestane treatment without surgery because of a PR or SD at 4 months.
      Adverse events, most of which were grade 1, occurred in <or=10% of patients.
      These results suggest that neoadjuvant exemestane treatment is effective and well
      tolerated in postmenopausal women with ER-positive breast cancer. Further studies
      are required to determine the optimal duration of neoadjuvant treatment and to
      identify response criteria that can more accurately predict long-term outcomes.

PMID- 18043898
TI  - Tumor susceptibility and prognosis of breast cancer associated with the G870A
      polymorphism of CCND1.
AB  - We aimed to investigate the role of CCND1 G870A polymorphism genetic and
      transcriptomic effects susceptibility in association with breast cancer
      carcinogenesis and clinical prognosis. A case-control study was conducted with
      the enrollment of 992 sporadic breast cancer patients and the corresponding 960
      normal controls from routine mammographic or sonographic screening for breast
      cancer between 1995 and 2003 in Taiwan. The 167 fragment spanning the G870A
      polymorphism in exon 4-intron 4 boundary was amplified to identify genotype of
      CCND1 (G870A) polymorphism. Competitive RT-PCR were further performed to
      investigate alternative transcript in four different specimens in association
      with immunohistochemistry markers. The results showed that AG and AA subgroup
      were at increased risk for developing breast cancer compared with the GG genotype
      by 19% (OR 1.19 (0.85-1.67)) and by 34% (OR 1.34 (0.04-1.74)), respectively. A870
      allele revealed a recessive tendency while GG and AA/AG subgroup was compared (OR
      1.35 (1.07-1.70)). AA genotype also had a higher risk in premenopausal women than
      postmenopausal ones. The recurrence-free survival was longer in patients with
      GG+AG than that in patients with AA (P = 0.034). A870 allele produced more
      transcript b both in malignant. There were significant correlations between
      several immunohistochemistry markers (such as Ki-67) and cyclin D1 or CDk4. We
      concluded CCND1 G870A polymorphism make significant contribution to breast cancer
      in the country with the preponderance of breast cancer in young women. The role
      of G870A polymorphism in alternative transcript was not only implicated in CCND1
      alternative splicing but also correlated with immunohistochemistry markers.

PMID- 18043899
TI  - Circulating endothelial progenitor cells correlate to stage in patients with
      invasive breast cancer.
AB  - Tumor growth and metastasis is dependent on the formation and assembly of new
      blood vessels, a process known as neo-angiogenesis. Both pre-existing and
      circulating vascular cells have been shown to contribute to the assembly of tumor
      neo-vessels in specific tumors. Mobilization of endothelial progenitor cells
      (EPCs) from the bone marrow constitutes a crucial step in the formation of de
      novo blood vessels, and levels of peripheral blood EPCs have been shown to be
      increased in certain malignant states. However, the role of circulating EPCs in
      breast cancer is largely unknown. We recruited twenty-five patients with biopsy
      proven invasive breast cancer at Weill Cornell Breast Center to participate in a
      pilot study investigating the correlation of circulating EPCs to extent of
      disease and initiation of chemotherapy. For each patient, a baseline sample was
      drawn before systemic treatment, and for seventeen of those patients, a second
      sample was taken after the first round of chemotherapy. Levels of peripheral
      blood EPCs, as defined by co-expression of CD133 and VEGFR2, were quantified by
      flow cytometry. Breast cancer patients with stage III & IV disease had
      statistically higher levels of circulating EPCs than did patients with stage I &
      II disease (median = 165,000 EPCs/5 x 10(6)MNCs vs. median = 6,920 EPCs/5 x
      10(6)MNCs, respectively, P < 0.0001). In addition, in late-stage patients, levels
      of EPCs demonstrated a statistically significant drop after initiation of
      chemotherapy (median = 162,500 EPCs/5 x 10(6)MNCs [pre] vs. median = 117,500
      EPCs/5 x 10(6)MNCs [post], P = 0.01). These results suggest that circulating EPCs
      may serve as a potential tumor biomarker in breast cancer and that EPCs may
      represent a plausible target for future therapeutic intervention.

PMID- 18043900
TI  - No association between BRCA mutations and sex ratio in offspring of Pakistani
      BRCA mutation carriers.

PMID- 18043902
TI  - [SIRS and ARDS as a result of drug injection in the shoulder region].
AB  - Bacterial infections with local inflammation or hematogenous spreading may occur
      after joint punctures and intra- or periarticular injections. The risk of severe
      infections increases in patients with diseases accompanied by low immunity, e.g.,
      gout, alcoholism, rheumatoid arthritis, and diabetes mellitus. Cases of septic
      omarthritis after intra-articular injection with fatal outcome after delayed
      onset of therapy are known. In our clinic we treated a female patient who
      previously received an injection in the shoulder region in a different facility.
      On admission she was suffering from an abscess of the surrounding soft tissues,
      systemic inflammatory response syndrome (SIRS), and adult respiratory distress
      syndrome (ARDS). Because the clinical picture was recognized early, we were able
      to prevent severe progression with organ failure. Another female patient
      developed a postinjection bacterial acromioclavicular arthritis followed by
      septic inflammatory response syndrome (SIRS) and eventually multiple organ
      failure (MOF). With inconspicuous clinical findings in the initial shoulder
      examination the bacterial arthritis was detected as the cause of sepsis only
      after intensive investigations.

PMID- 18043901
TI  - Harnessing hypoxic adaptation to prevent, treat, and repair stroke.
AB  - The brain demands oxygen and glucose to fulfill its roles as the master regulator
      of body functions as diverse as bladder control and creative thinking. Chemical
      and electrical transmission in the nervous system is rapidly disrupted in stroke
      as a result of hypoxia and hypoglycemia. Despite being highly evolved in its
      architecture, the human brain appears to utilize phylogenetically conserved
      homeostatic strategies to combat hypoxia and ischemia. Specifically, several
      converging lines of inquiry have demonstrated that the transcription factor
      hypoxia-inducible factor-1 (HIF1-1) mediates the activation of a large cassette
      of genes involved in adaptation to hypoxia in surviving neurons after stroke.
      Accordingly, pharmacological or molecular approaches that engage hypoxic
      adaptation at the point of one of its sensors (e.g., inhibition of HIF prolyl 4
      hydroxylases) leads to profound sparing of brain tissue and enhanced recovery of
      function. In this review, we discuss the potential mechanisms that could subserve
      protective and restorative effects of augmenting hypoxic adaptation in the brain.
      The strategy appears to involve HIF-dependent and HIF-independent pathways and
      more than 70 genes and proteins activated transcriptionally and post
      transcriptionally that can act at cellular, local, and system levels to
      compensate for oxygen insufficiency. The breadth and depth of this homeostatic
      program offers a hopeful alternative to the current pessimism towards stroke
      therapeutics.

PMID- 18043903
TI  - [Are contrast agents containing gadolinium only counter-indicated for dialysis
      patients?].

PMID- 18043904
TI  - [Costs due to urinary tract infections in Germany. An estimation based on the
      data from the German National Nosocomial Infections Surveillance System].
AB  - BACKGROUND: We estimated the avoidable costs due to nosocomial urinary tract
      infections (UTI) based on the data of the German National Nosocomial Infections
      Surveillance System (KISS). METHODS: The incidence of nosocomial UTI derived from
      KISS reference data. The overall number of patient days was obtained from the
      "Statistische Bundesamt" (German Federal Office of Statistics). Expected costs
      for a single UTI were estimated according to data published in the medical
      literature. RESULTS: On average, there were 1.87 UTI on intensive care units
      (ICU) and 0.81 UTI on peripheral wards per 1,000 patient days; 4.5% of the annual
      146.1 million patient days in German hospitals were contributed by ICUs. In
      total, there are approximately 155,000 nosocomial UTI every year. Each UTI leads
      to costs of about 1,000 euros; 20% of all nosocomial infections are preventable.
      CONCLUSIONS: Just for nosocomial UTI, appropriate infection control measures may
      reduce the annual health care costs by 14,500 euros for every German hospital.

PMID- 18043905
TI  - HbA1c measured in stored erythrocytes and mortality rate among middle-aged and
      older women.
AB  - AIMS/HYPOTHESIS: Diabetes is known to increase mortality rate, but the degree to
      which mild hyperglycaemia may be associated with the risk of death is uncertain.
      We examined the association between HbA1c measured in stored erythrocytes and
      mortality rate in women with and without diabetes. METHODS: We conducted a cohort
      study of 27,210 women>or=45 years old with no history of cardiovascular disease
      or cancer who participated in the Women's Health Study, a randomised trial of
      vitamin E and aspirin. RESULTS: Over a median of 10 years of follow-up, 706 women
      died. Proportional hazards models adjusted for age, smoking, hypertension, blood
      lipids, exercise, postmenopausal hormone use, multivitamin use and C-reactive
      protein were used to estimate the relative risk of mortality. Among women without
      a diagnosis of diabetes and HbA1c<5.60%, those in the top quintile (HbA1c 5.19
      5.59%) had a relative risk of mortality of 1.28 (95% CI 0.98-1.69, p value for
      linear trend=0.14) compared with those with HbA1c 2.27-4.79%. Women with HbA1c
      5.60-5.99% and no diagnosis of diabetes had a 54% increased risk of mortality
      (95% CI 1-136%) compared with those with HbA1c 2.27-4.79%. HbA1c was
      significantly associated with mortality across the range 4.50-7.00% (p value for
      linear trend=0.02); a test of deviation from linearity was not statistically
      significant (p=0.67). Diabetic women had more than twice the mortality risk of
      non-diabetic women. CONCLUSIONS/INTERPRETATION: This study provides further
      evidence that chronic mild hyperglycaemia, even in the absence of diagnosed
      diabetes, is associated with increased risk of mortality. ClinicalTrials.gov ID
      no.: NCT00000479.

PMID- 18043906
TI  - A technique for arthroscopic fasciotomy for the chronic exertional tibialis
      anterior compartment syndrome.
AB  - Chronic exertional anterior compartment syndrome (CECS) is a condition that
      causes pain over the front of the shin bone that usually occurs in physically
      active people, especially runners. It may require sometimes an immediate
      fasciotomy. A longitudinal incision just over the fibula has used as surgical
      treatment bad cosmetic appearance. Although nowadays mini surgical incisions are
      preferred. The aim of this study to evaluate a simple fasciotomy technique with a
      minimal incision by using arthroscope. Nine legs of six patients that diagnosed
      as CECS has underwent fasciotomy operation with a 1 cm incision. Complaints had
      disappeared after operation. The mean follow-up time is 2 years. The results were
      good all of the patients and they never experienced exertional pain episodes. The
      arthroscopic assisted mini incisional fasciotomy technique has advantage such as
      early rehabilitation and good cosmetic appearance.

PMID- 18043907
TI  - Transcriptional activity of Pseudomonas aeruginosa fhp promoter is dependent on
      two regulators in addition to FhpR.
AB  - The regulation of flavohemoglobin expression is complex and depending on its host
      organism requires a wide variety of different transcriptional regulators. In
      Pseudomonas aeruginosa, the flavohemoglobin (Fhp) and its cognate regulator FhpR
      form an NO-sensing and detoxifying system regulated by their common bidirectional
      promoter Pfhp/PfhpR. The intergenic fhp-fhpR region of P. aeruginosa PAO1 was
      used as a bait to isolate proteins affecting the transcription of fhp and fhpR.
      In addition to the FhpR, we identified two previously uncharacterized P.
      aeruginosa proteins, PA0779 and PA3697. Both PA0779 and PA3697 were found to be
      essential for NO3(-) and NO2(-) induced Pfhp activity under aerobic and low
      oxygen conditions, and needed for the full function of Pfhp/PfhpR as NO
      responsive regulatory circuit under aerobic conditions. In addition, we show that
      the transcriptional activity of PfhpR is highly inducible upon addition of SNP
      under aerobic conditions, but not by NO3(-), NO2(-) or under low-oxygen
      conditions, supporting the findings that FhpR is not the only factor affecting
      flavohemoglobin expression in P. aeruginosa.

PMID- 18043908
TI  - Effects of intranasal methamphetamine on metacognition of agency.
AB  - BACKGROUND: Although methamphetamine abuse has been associated with cognitive
      deficits, few studies have investigated the acute effects of the drug on complex
      cognitive performance. This study evaluated the acute effects of intranasal
      methamphetamine on a computerized task measuring metacognition of agency.
      PROCEDURE: Ten nontreatment seeking methamphetamine abusers (2F, 8M) completed
      this four-session, within-participant, double-blind laboratory study; during each
      session, participants received one of four doses (0, 12, 25, or 50 mg/70 kg) and
      completed the metacognition of agency task. In this task, participants were
      instructed to "catch" falling targets with a mouse and then provide metacognitive
      judgments about their feelings of control. RESULTS: Following placebo, judgments
      of agency were greater under optimal task conditions compared with less than
      optimal task conditions. Relative to placebo, the 12-mg dose improved task
      performance, increased judgments of agency under the optimal condition, and
      decreased judgments of agency under the less than optimal condition. By contrast,
      the larger doses (25 and 50 mg) increased judgments of agency only under the
      optimal condition but disrupted performance under the less than optimal
      condition. CONCLUSION: These data show that a low intranasal methamphetamine dose
      enhanced judgments of agency and performance, while larger doses produced limited
      effects.

PMID- 18043909
TI  - Studies on the analytical performance of a non-covalent coating with N,N
      didodecyl-N,N-dimethylammonium bromide for separation of basic proteins by
      capillary electrophoresis in acidic buffers in 25- and 50-microm capillaries.
AB  - Capillaries (25- and 50-microm inner diameter) coated with a double-alkyl-chain
      cationic surfactant N,N-didodecyl-N,N-dimethylammonium bromide (DDAB) were used
      for the separation of four basic standard proteins in buffers of pH 4 at various
      ionic strengths. The choice of buffer is critical for the analytical performance.
      Ammonium ions must be avoided in the buffer used in the non-covalent coating
      procedure owing to competition with the surfactant. Phosphate buffer gave a
      better separation performance than some volatile buffers; the reason seems to be
      a complex formation between the proteins and dihydrogenphosphate ions, which
      decreases tendencies for adsorption to the capillary surface. The DDAB coating
      was easy to produce and stable enough to permit, without recoating, consecutive
      separations of the proteins for up to 100 min with good precision in migration
      times and peak areas. A strong electroosmotic flow gives rapid separations, which
      is of special importance when commercial instruments are used, since the choice
      of the length of the capillary is restricted.

PMID- 18043910
TI  - Attenuation of N2 amplitude of laser-evoked potentials by theta burst stimulation
      of primary somatosensory cortex.
AB  - Theta burst stimulation (TBS) is a special repetitive transcranial magnetic
      stimulation (rTMS) paradigm, where bursts of low-intensity stimuli are applied in
      the theta frequency. The aim of this study was to investigate the effect of
      neuronavigated TBS over primary somatosensory cortex (SI) on laser-evoked
      potentials (LEPs) and acute pain perception induced with Tm : YAG laser
      stimulation. The amplitude changes of the N1, N2, and P2 components of LEPs and
      related subjective pain rating scores of 12 healthy subjects were analyzed prior
      to and following continuous TBS (cTBS), intermittent TBS (iTBS), intermediate TBS
      (imTBS), and sham stimulation. Our results demonstrate that all active TBS
      paradigms significantly diminished the amplitude of the N2 component, when the
      hand contralateral to the site of TBS was laser-stimulated. Sham stimulation
      condition had no significant effect. The subjective pain perception also
      decreased during the experimental sessions, but did not differ significantly from
      the sham stimulation condition. The main finding of our study is that TBS over SI
      diminished the amplitude of the N2 component evoked from the contralateral side
      without any significant analgesic effects. Furthermore, imTBS produced responses
      similar to those observed by other forms of TBS induced excitability changes in
      the SI.

PMID- 18043912
TI  - Haemodynamic simulation of aneurysm coiling in an anatomically accurate
      computational fluid dynamics model: technical note.
AB  - INTRODUCTION: Computational fluid dynamics (CFD) is a numerical technique that is
      used for studying haemodynamic parameters in cerebral aneurysms. As it is now
      possible to represent an anatomically accurate intracranial aneurysm in a
      computational model, we have attempted to simulate its endosaccular occlusion
      with coils and demonstrate the haemodynamic changes induced. This is the first
      attempt to use this particular porous medium-based method for coiling simulation
      in a CFD model, to our knowledge. METHODS: Datasets from a rotational 3-D digital
      subtraction angiogram of a recently ruptured anterior communicating aneurysm were
      converted into a 3-D geometric model and the discretized data were processed
      using the computational technique developed. Coiling embolisation simulation was
      achieved by impediment of flow through a porous medium with characteristics
      following a series of embolisation coils. Haemodynamic parameters studied were:
      pressure distribution on the vessel wall, blood velocity and blood flow patterns.
      RESULTS: Significant haemodynamic changes were detected after deployment of the
      first coil. Similar, but less dramatic changes occurred during subsequent stages
      of coiling. The blood flow patterns became less vortical in the aneurysm sac as
      velocity decreased to stagnation and the wall pressure at the fundus was
      gradually reduced. Furthermore, the haemodynamic characteristics developed at the
      area of the neck remnant could form the basis for assessing the likelihood of
      delayed coil compaction and aneurysm regrowth. CONCLUSION: Appropriate
      computational techniques show great promise in simulating the haemodynamic
      behaviour of the various stages in coil embolisation and may be a potentially
      valuable tool in interventional planning and procedural decision-making.

PMID- 18043913
TI  - Metals and membranes in neuroscience.

PMID- 18043911
TI  - Inhibition of metoprolol metabolism and potentiation of its effects by paroxetine
      in routinely treated patients with acute myocardial infarction (AMI).
AB  - OBJECTIVE: To investigate the influence of paroxetine on metoprolol
      concentrations and its effect in patients treated for acute myocardial infarction
      (AMI) who are routinely given paroxetine as a co-treatment of depression.
      METHODS: We recruited 17 depressed AMI patients who received metoprolol as a
      routine part of their therapy (mean dose 75 +/- 39 mg/day). Patients were
      genotyped for CYP2D6 3, 4 and gene duplication. Metoprolol and alpha-hydroxy
      metoprolol were analyzed in plasma 0, 2, 6 and 12 h post-dose. Heart rates (HR)
      at rest were registered after each sampling. Paroxetine 20 mg daily was then
      administered, and all measurements were repeated on day 8. RESULTS: All patients
      were genotypically extensive metabolizers (EMs) (nine with 1/1 and eight with 1/3
      or 4). Following the administration of paroxetine, mean metoprolol areas under
      the concentration-time curve (AUC) increased (1064 +/- 1213 to 4476 +/- 2821 nM x
      h/mg per kg, P = 0.0001), while metabolite AUCs decreased (1492 +/- 872 to 348 +/
      279 n M x h/mg per kg, P < 0.0001), with an increase of metabolic ratios (MR)
      (0.9 +/- 1.3 to 26 +/- 29; P < 0.0001). Mean HRs were significantly lower after
      the study week at each time point. Mean area under the HR versus time curve
      (AUEC) decreased (835 +/- 88 to 728 +/- 84 beats x h/min; P = 0.0007). Metoprolol
      AUCs correlated with patients' AUECs at the baseline (Spearman r = -0.64, P <
      0.01), but not on the eighth day of the study. A reduction of metoprolol dose was
      required in two patients due to excessive bradycardia and severe orthostatic
      hypotension. No other adverse effects of the drugs were identified. CONCLUSION: A
      pronounced inhibition of metoprolol metabolism by paroxetine was observed in AMI
      patients, but without serious adverse effects. We suggest, however, that the
      metoprolol dose is controlled upon initiation and withdrawal of paroxetine.

PMID- 18043914
TI  - Studies of distribution, location and dynamic properties of EGFR on the cell
      surface measured by image correlation spectroscopy.
AB  - In this work, we have studied the distribution and dynamic properties of
      Epidermal Growth Factor (EGF) receptors in the plasma membrane of fixed and live
      cells as well as the extent of co-localization of this transmembrane protein with
      proteins specific for three-membrane microdomains: membrane rafts, caveolae and
      clathrin-coated pits. This was achieved using a family of image-processing tools
      called image correlation spectroscopy (ICS), image cross-correlation spectroscopy
      (ICCS) and dynamic image correlation spectroscopy (DICS). Our results indicate
      that EGFR is diffusely distributed on the cell surface at 37 degrees C and
      aggregates as the temperature is lowered to 4 degrees C. This aggregation takes
      place within 15 min and is reversible. Changes in temperature also affect the
      diffusion of EGFR by two orders of magnitude. The dynamic properties of EGFR are
      similar to the dynamic properties of a GPI-anchored protein known to be present
      in membrane rafts, which motivated us to explore the extent of co-localization of
      EGFR with this membrane raft protein using ICCS. Our results indicate that more
      than half of the EGFR population is present in membrane rafts and smaller
      percentages are present in caveolae and clathrin-coated pits.

PMID- 18043915
TI  - Marine lysozyme from a marine bacterium that inhibits angiogenesis and tumor
      growth.
AB  - Recent studies suggest that lysozyme, rich in hen egg, has an antitumor function.
      In the present study, we investigated the antitumor and antiangiogenesis effects
      of a newly isolated marine lysozyme both in vitro and in vivo. First, we showed
      that this marine-derived lysozyme specifically inhibits the proliferation of
      endothelial cells (ECV304) in a dose-dependent manner with no cytotoxicity
      (IC(50) = 3.64 microM). Second, we showed that this marine lysozyme directly
      suppresses neovascularization in chicken embryos using chorioallantoic membrane
      assay. Third, we demonstrated that this marine lysozyme markedly inhibits tumor
      growth in mice bearing either sarcoma 180 or hepatoma 22. Unexpectedly, hen egg
      lysozyme has no effects on the proliferation of endothelial cells in vitro or
      neovascularization in chicken embryos or tumor growth in nude mice at the same
      dosage range. Taken together, our studies clearly show that the newly identified
      marine lysozyme is a potent antitumor molecule, which may inhibit tumor growth
      and inhibit angiogenesis. We believe that this marine lysozyme may have a
      therapeutic value in antitumor drug development.

PMID- 18043916
TI  - Pathway, inhibition and regulation of methyl tertiary butyl ether oxidation in a
      filamentous fungus, Graphium sp.
AB  - The filamentous fungus Graphium sp. (ATCC 58400) co-metabolically oxidizes the
      gasoline oxygenate methyl tertiary butyl ether (MTBE) after growth on gaseous n
      alkanes. In this study, the enzymology and regulation of MTBE oxidation by
      propane-grown mycelia of Graphium sp. were further investigated and defined. The
      trends observed during MTBE oxidation closely resembled those described for
      propane-grown cells of the bacterium Mycobacterium vaccae JOB5. Propane-grown
      mycelia initially oxidized the majority ( approximately 95%) of MTBE to tertiary
      butyl formate (TBF), and this ester was biotically hydrolyzed to tertiary butyl
      alcohol (TBA). However, unlike M. vaccae JOB5, our results collectively suggest
      that propane-grown mycelia only have a limited capacity to degrade TBA. None of
      the products of MTBE exerted a physiologically relevant regulatory effect on the
      rate of MTBE or propane oxidation, and no significant effect of TBA was observed
      on the rate of TBF hydrolysis. Together, these results suggest that the
      regulatory effects of MTBE oxidation intermediates proposed for MTBE-degrading
      organisms such as Mycobacterium austroafricanum are not universally relevant
      mechanisms for MTBE-degrading organisms. The results of this study are discussed
      in terms of their impact on our understanding of the diversity of aerobic MTBE
      degrading organisms and pathways and enzymes involved in these processes.

PMID- 18043917
TI  - Heterologous expression of heterodimeric laccase from Pleurotus ostreatus in
      Kluyveromyces lactis.
AB  - Among the laccases produced by the white-rot fungus Pleurotus ostreatus, there
      are two closely related atypical isoenzymes, POXA3a and POXA3b. These isoenzymes
      are endowed with quaternary structure, consisting of two subunits very different
      in size. The POXA3 large subunit is clearly homologous to other known laccases,
      while the small subunit does not show significant homology with any protein in
      data banks. To investigate on the singular structure of the POXA3 complex, a new
      system for recombinant expression of heterodimer proteins in the yeast
      Kluyveromyces lactis has been set up. A unique expression vector has been used
      and the cDNAs encoding the two subunits have been cloned under the control of the
      same bi-directionally acting promoter. Expression of the large subunit alone and
      co-expression of both subunits in the same host have been demonstrated and the
      properties of the recombinant proteins have been compared. Clones expressing the
      large subunit alone exhibited always notably lower activity than those expressing
      both subunits. In addition to the activity increase, the presence of the small
      subunit led to a significant increase of laccase stability. Therefore, a role of
      the small subunit in POXA3 stabilisation is suggested.

PMID- 18043918
TI  - Radioguided occult lesion localisation in breast cancer using an intraoperative
      portable gamma camera: first results.
AB  - PURPOSE: The role of the radioguided occult lesion localisation (ROLL) technique
      in breast cancer has been increasing in recent years. One of the important
      drawbacks of such a technique is radiotracer spillage within the mammary gland
      that makes the precise lesion resection difficult, and this requires the use of a
      hook-wire collocation to reach the lesion. The possibility of obtaining an
      intraoperative image of the specimen could help to confirm whether the lesion is
      correctly removed. Some types of portable gamma cameras have been designed, but
      up to now, intraoperative use has been confined to surgery of parathyroid
      adenomas and sentinel lymph node location. The aim of the study was to value the
      usefulness of an intraoperative gamma camera to assess the resection of non
      palpable breast lesions. MATERIALS AND METHODS: The study involved 42 women
      diagnosed with non-palpable early breast cancer. Lymphoscintigraphy was performed
      on the day before surgery by injection of (99m)Tc-labelled nanocolloid. During
      surgery a gamma probe was used to guide the surgeon, and afterwards images of the
      surgical bed and the tumoral specimen were acquired by means of a portable gamma
      camera, fitted with a pinhole collimator. A (99m)Tc pointer was used to draw an
      outline image around the specimen. RESULTS: On lymphoscintigraphy, radiotracer
      was concentrated in 31 cases. During surgery, all lesions were removed. In the
      images acquired by the portable gamma camera, the lesion was centred inside the
      surgical specimen in 23 of 42 cases, non-centred in 15 and in contact in 4 cases.
      Congruence of 60% was found between the intraoperative images and the
      histopathological results. The posterior margin was the most frequently involved.
      The whole acquisition time for the tumoral specimen with its margins was 5 min at
      most. CONCLUSION: The use of portable gamma cameras in theatre is in an early
      phase. The short period of time required during the surgical procedure will allow
      the surgical team to improve this technique until it can replace hand-held
      probes. The intraoperative acquisition of such images can predict the involvement
      of surgical margins, avoiding future surgical procedures.

PMID- 18043919
TI  - I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in
      heart failure patients: insights from a retrospective European multicenter study.
AB  - PURPOSE: Single-center experiences have shown that myocardial meta
      iodobenzylguanidine (mIBG) uptake has prognostic value in heart failure (HF)
      patients. To verify these observations using a rigorous clinical trial
      methodology, a retrospective review and prospective quantitative reanalysis was
      performed on a series of cardiac (123)I-mIBG scans acquired during a 10-year
      period at six centers in Europe. METHODS: (123)I-mIBG scans obtained on 290 HF
      patients [(262 with left ventricular ejection fraction (LVEF) < 50%)] from 1993
      to 2002 were reanalyzed using a standardized methodology to determine the heart
      to-mediastinum ratio (H/M) on delayed planar images. All image results were
      verified by three independent reviewers. Major cardiac events [MCEs; cardiac
      death, cardiac transplant, potentially fatal arrhythmia (including implantable
      cardioverter-defibrillator discharge)] during 24-month follow-up were confirmed
      by an adjudication committee. RESULTS: MCEs occurred in 67 patients (26%): mean
      H/M ratio was 1.51 +/- 0.30 for the MCE group and 1.97 +/- 0.54 for the non-MCE
      group (p < 0.001). Two-year event-free survival using an optimum H/M ratio
      threshold of 1.75 was 62% for H/M ratio less than 1.75, 95% for H/M ratio greater
      than or equal to 1.75 (p < 0.0001). Logistic regression showed H/M ratio and LVEF
      as the only significant predictors of MCE. Using the lower and upper H/M
      quartiles of 1.45 and 2.17 as high- and very low-risk thresholds, 2-year event
      free survival rates were 52% and 98%, respectively. Among patients with LVEF < or
      = 35% and H/M > or = 1.75 (n = 73), there were nine MCEs because of progressive
      HF and only one because of an arrhythmia. CONCLUSION: Application of a clinical
      trial methodology via the retrospective reanalysis of (123)I-mIBG images confirms
      the previously reported prognostic value of this method in HF patients, including
      potential identification of a quantitative threshold for low risk for cardiac
      mortality and potentially fatal ventricular arrhythmias.

PMID- 18043920
TI  - Emergence of the alumina matrix composite in total hip arthroplasty.
AB  - Pure alumina ceramic has been in clinical use in orthopaedics since 1971 and,
      currently, up to 5 million components have been implanted. Alumina offers
      advantages like stability, biocompatibility and low wear; however, it has limited
      strength. Applications are limited by design considerations. Engineers in
      biomaterials have worked on improving the performance of the material by
      optimising the manufacturing process. To fulfil surgeons' and patients'
      increasingly exacting requirements, ceramists have also developed a new ceramic
      composite, the alumina matrix composite (AMC). This material combines the great
      principles of the reinforcement of ceramics with its tribological qualities and
      presents a better mechanical resistance than alumina. The examination of the
      tribological situation of AMC, especially under the challenging conditions of
      hydrothermal ageing, shows the aptitude of this material in wear applications.
      The US Food and Drug Administration (FDA) has approved ceramic ball heads
      articulating against polyethylene inserts. Since its introduction, more than
      65,000 ball heads and 40,000 inserts of AMC have been implanted. With a 6-year
      follow up, no complication has been reported to the manufacturer. Improved
      toughness and the excellent wear of AMC makes it a potentially more flexible
      alternative to the more traditional alumina for hip prostheses.

PMID- 18043921
TI  - Isokinetic evaluation of knee extensor/flexor muscle strength in patients with
      hypermobility syndrome.
AB  - Benign joint hypermobility syndrome (BJHS) is a syndrome with musculoskeletal
      pain originating from the increased laxity of the joints and the ligaments. The
      study was to compare the isokinetic strength of knee extensor/flexor muscles of
      BJHS patients with healthy controls. Forty patients diagnosed as having BJHS with
      Brighton criteria and 45 years of age, height and weight-matched healthy controls
      were recruited for the study. Isokinetic testing was performed with isokinetic
      dynamometry of Biodex System 3Pro and measurements were recorded at knee
      extension/flexion pattern concentrically at 60, 180, and 240 degrees/s angular
      velocities. The study group was also evaluated for functional impairment and pain
      by HAQ and VAS respectively. Knee extensor muscle strength was significantly
      lower in the patient group compared with the controls. It was hypothesized that
      the muscle weakness in the study group was related to lengthening of the
      quadriceps muscle and pain-related inactivity as well as joint instability and
      proprioception defect.

PMID- 18043922
TI  - The role of frequency, phase and time for processing of amplitude modulated
      signals by grasshoppers.
AB  - Acoustic signals consist of pressure changes over time and can thus be analyzed
      in the frequency- or in the time-domain. With behavioural experiments we
      investigated which frequency components (FC) are necessary for the recognition of
      the periodic envelope of the conspecific song by females of the grasshopper
      Chorthippus biguttulus. Further, we determined up to which frequency component
      phase information is required which would indicate processing in the time domain.
      Responses of females revealed that signals composed of FC between 10 and 50 Hz
      are sufficient for recognition of the song envelope. A systematic reduction in
      the number of FC showed that no single frequency component was required; signals
      without the fundamental frequency were still highly attractive and only three FC
      may be sufficient for song recognition. Phase changes for frequencies up to 40 Hz
      strongly changed the attractiveness of song signals but only little at 50 Hz.
      Females were also tested with rectangular signals in which pause duration was
      varied. Evidently, and despite the high attractiveness of song signals with a
      "missing fundamental", females evaluated the attractiveness of signals in the
      time-domain, since the selectivity for pause duration predicted the responses to
      signals composed from FC well.

PMID- 18043923
TI  - Adult tethered cord syndrome mimicking lumbar disc disease.
AB  - OBJECT: This paper reports four tethered cord cases who initially applied with
      lumbar disk disease symptoms. MATERIALS AND METHODS: All of them were
      investigated by magnetic resonance imaging (MRI) and somatosensory evoked
      potential (SSPE). In two patients, MRI revealed thick and fatty filum terminale,
      while in remaining two, the filum terminale appeared as normal in thickness. SSEP
      revealed pathological conduction values in all, and it was the main indicator for
      surgical sectioning in patients especially with normal MRI investigations. All
      patients had benefit from the surgical sectioning of the fila terminalia with
      either thick and fatty or normal appearance. CONCLUSION: A particular patient
      with lumbar disc disease symptoms having normal MRI should also be investigated
      for tight filum terminale. If there is no pathological appearance in MRI
      investigation (both in regard to disc herniation and thick and fatty filum
      terminale), SSEP investigation should be done to check whether a conduction block
      or delay is present, indicating cord tethering.

PMID- 18043924
TI  - Multiple short-segment laminoplasties in children: a novel technique to avoid
      postoperative spinal deformity.
AB  - INTRODUCTION: Spinal deformity is a recognized important complication after
      laminectomies, especially in children. Even with laminoplasties, spinal deformity
      is a concern, especially when laminoplasties involve multiple levels. The author
      reports a novel technique to avoid postoperative spinal deformity using multiple
      short-segment replacement laminoplasties to access pathology over a long segment
      of the intraspinal space. REPORT: The technique was used to evacuate an organized
      extradural hematoma from C4 to T9 in a 9-month-old infant with incomplete
      quadriplegia. Three separate, short-segment, and superiorly reflected
      laminoplasties (C5-C7; T2-T4; T6-T8) were performed, leaving intact the laminae
      (T1; T5) between each laminoplasty flap. At 1 year postoperatively, there was
      complete neurological recovery and no spinal deformity. The laminae re-fused
      anatomically. CONCLUSIONS: Multiple short-segment laminoplasties allow good
      access to a long intraspinal segment, may preserve the stability of the spine,
      prevent spinal deformity, allow good reconstitution of the laminar anatomy, and
      facilitate surgical stabilization should that be required in the future. This
      technique may be applicable to other intraspinal lesions, such as tumors.

PMID- 18043925
TI  - Recurrent nephrogenic adenoma in a 10-year-old boy with prune belly syndrome : a
      case presentation.
AB  - Nephrogenic adenoma is a rare benign lesion of the urinary tract that is
      associated with a history of irritation or injury of the urothelium. Predisposing
      factors include infection, calculi, surgery, trauma, and renal transplantation.
      Nephrogenic adenoma commonly presents with lower urinary tract symptoms or
      hematuria. We present the case of recurrent nephrogenic adenoma in a 10-year-old
      boy with a history of prune belly syndrome and discuss management of this disease
      in the pediatric population. To our knowledge this represents the first reported
      case of recurrent nephrogenic adenoma associated with prune belly syndrome.

PMID- 18043926
TI  - Life-threatening rectal necrosis after injection sclerotherapy for haemorrhoids.

PMID- 18043927
TI  - Doxycycline-coated sutures improve mechanical strength of intestinal anastomoses.
AB  - BACKGROUND AND AIMS: After resection and repair of the intestines, tissue
      degradation leads to weakening of the repair site and risk of postoperative
      leakage. Matrix metalloproteinases (MMPs) are thought to be responsible for
      collagenolysis in the direct vicinity of surgical sutures in many tissues.
      Several experimental studies show that MMP inhibitors administered systemically
      alleviate postoperative weakening of intestinal anastomoses. We hypothesised that
      local delivery of MMP inhibitors would achieve a similar effect. MATERIALS AND
      METHODS: Implementing a novel method for the coating of biomaterials, we coated
      sutures with a cross-linked fibrinogen film and bound the MMP inhibitor
      doxycycline into this film. The sutures were then used in a standard rat model
      for evaluating mechanical properties of colonic anastomoses 3 days after surgery.
      RESULTS: The breaking strength of the anastomoses on the critical third day after
      operation was 17% higher with doxycycline-coated sutures compared to controls (P
      = 0.026). Energy uptake at failure was enhanced by 20% (P = 0.047). CONCLUSION:
      Drug delivery by means of MMP-inhibitor-coated sutures appears to improve tissue
      integrity during anastomotic repair and may reduce postoperative complications.

PMID- 18043928
TI  - Lack of thrombospondin-1 increases angiogenesis in a model of chronic
      inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Vascular abnormalities and expression of pro-angiogenic
      factors are observed in inflammatory bowel diseases (IBD). In this study, the
      role of thrombospondin-1 (TSP-1), an antiangiogenic protein, was analyzed using
      the dextran sulfate sodium (DSS) model for IBD. MATERIALS AND METHODS: Wild-type
      (WT) and thrombospondin-1-deficient (TSP-1(-/-)) mice were subjected to four
      cycles (7 days) of DSS. Basic fibroblast growth factor (bFGF), vascular
      endothelial growth factor (VEGF), transforming growth factor beta 1 (TGFbeta-1),
      and pro-apoptotic proteins such as Fas and its ligand (FasL) were determined by
      enzyme-linked immunosorbent assay. Double immunohistochemistry for cluster of
      differential 31 (CD31) and panendothelial cell antigen-32 antibodies was
      performed for detecting blood vessels. The terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling assay was also performed for identifying
      apoptotic cells. Inflammation, dysplasia, microvascular density (MVD), apoptotic
      indices (AI), protein 53 (p53), and beta-catenin expression were determined.
      RESULTS: VEGF and bFGF protein levels and MVD were higher in the TSP-1(-/-) mice
      (p = 0.0312, p = 0.0246, and p = 0.0085, respectively). AI in the endothelial
      cells (EC) and FasL levels were significantly lower in TSP-1(-/-) compared to WT
      mice (p = 0.0042 and p = 0.0362, respectively). Dysplasia was detected in 66% of
      TSP-1(-/-) mice compared to 14% in WT mice. Hscores of ss-catenin and areas
      overexpressing p53 were higher in TSP-1(-/-) mice (p = 0.0002 and p = 0.0339,
      respectively). CONCLUSION: TSP-1 may decrease angiogenesis by reducing the levels
      of pro-angiogenic factors and inducing apoptosis in EC through the Fas or FasL
      pathway. These findings, along with the increased overexpression of p53 and beta
      catenin in TSP-1(-/-) mice, underline its role in carcinogenesis.

PMID- 18043929
TI  - Time and rate of sinus formation in pilonidal sinus disease.
AB  - BACKGROUND: and aims To elicit mechanisms and timing of sinus development, the
      role of age at onset of symptoms, symptomatic disease duration, and consecutive
      number of sinuses were investigated. MATERIALS AND METHODS: Analysis of 1,962
      medical records of patients admitted for primary surgical pilonidal sinus
      treatment. RESULTS: Sinus number ranged from 1 to 16 (median 2), with chronic
      pilonidal disease showing more sinuses than acute disease (mean 2.6 vs 2.1
      sinuses; p < 0.0001; Kolmogorov-Smirnov). Disease duration in chronic pilonidal
      disease was not linked to sinus formation (p = 0.98; Spearman). In acute
      pilonidal disease, duration was linked to the development of six sinuses per
      1,000 symptomatic disease years (p = 0.0001; Spearman). A larger sinus number
      correlated with earlier onset of symptoms (p = 0.009; Spearman). CONCLUSION: Long
      standing chronic disease does not produce sinus per se. As sinus does not
      substantially arise during the course of symptomatic disease, there must be a
      time before the start of symptomatic disease when the sinus originates. These
      findings suggest that sinus can only be acquired up to a certain age, even if
      occupational exposure continues.

PMID- 18043930
TI  - Sagittal alignment of the lower extremity while standing in Japanese male.
AB  - There is little information available regarding the sagittal mechanical axis of
      the lower extremity of normal subjects under weight-bearing conditions. The
      purpose of this study was to determine the sagittal alignment of the lower
      extremity under such conditions. Anteroposterior and lateral radiographs were
      taken of the 20 lower extremities of 10 healthy male Japanese volunteers (mean
      age, 27 years) while standing. The coronal mechanical axis passed through 33.9%
      medial to the proximal tibial articulating surface. The sagittal mechanical axis
      passed through 38.0% anterior to the distal femoral condyle and 27.9% anterior to
      the proximal tibial articulating surface, and also passed 5.2 mm anterior to the
      intercondylar notch. Our study therefore showed that the coronal and sagittal
      mechanical axes of the lower extremity do not always pass through the center of
      the knee. This has important implications for alignment in surgery of lower
      extremities such as total knee arthroplasty and osteotomy.

PMID- 18043931
TI  - Recordings of the optical intrinsic signal from the middle turbinate in response
      to olfactory and trigeminal stimulation: a pilot study.
AB  - Responses from the middle turbinate elicited by olfactory and trigeminal stimuli
      were studied using the intrinsic optical signal (IOS) recording technique. Nasal
      cavity was illuminated by 617 nm light. Olfactory (H2S) or trigeminal (CO2)
      stimuli of 5-s duration were presented using a computer-controlled olfactometer;
      IOS responses were captured by a special camera. Averages across five individual
      IOS recordings were analyzed. When the nasal cavity was exposed to H2S, a
      significant change of the IOS was found; responses to CO2 were even more
      pronounced. The present results argue for the idea that the IOS is an indicator
      of intranasal chemosensory activation.

PMID- 18043932
TI  - Clinical subgroups and antifungal susceptibilities in fungal culture-positive
      patients with chronic rhinosinusitis.
AB  - The goal of this study was to investigate clinical characteristics of chronic
      rhinosinusitis (CRS) in patients with positive fungal cultures. Fungal cultures
      were taken from 55 CRS patients and 20 healthy volunteers. Susceptibilities of
      isolated fungi to fluconazole, amphotericin B, itraconazole, voriconazole, and
      caspofungin were determined in CRS patients. Fungi grew in the cultures from 44
      (80%) CRS patients and 17 (85%) healthy volunteers. Of the patients with positive
      fungal cultures, 5 (11.3%) had fungal hypersensitivity (FH), and 21 (47.7%) had
      eosinophilic mucin (EM). Fungal culture-positive patients with EM were more
      likely to be associated with presence of polyps and higher CT scores than those
      without EM (P < 0.05). All the patients with FH had EM and polyps, and CT scores
      of those patients were highest. The sensitivity rates of fungal isolates were
      97.8% for amphotericin B, caspofungin, and voriconazole; 74.4% for itraconazole;
      and 6.4% for fluconazole. The presence of EM with or without FH leaded to more
      extended CRS, but a part of positive fungal cultures were together with EM in
      patients with CRS. Sensitivity to antifungal agents, except fluconazole, was
      high. Because many factors can contribute to the pathogenesis of CRS, medical
      treatment should be considered on a case-by-case basis.

PMID- 18043933
TI  - Short-term effects of normobaric hypoxia on the human spleen.
AB  - Spleen contraction resulting in an increase in circulating erythrocytes has been
      shown to occur during apnea. This effect, however, has not previously been
      studied during normobaric hypoxia whilst breathing. After 20 min of horizontal
      rest and normoxic breathing, five subjects underwent 20-min of normobaric hypoxic
      breathing (12.8% oxygen) followed by 10 min of normoxic breathing. Ultrasound
      measurements of spleen volume and samples for venous hemoglobin concentration
      (Hb) and hematocrit (Hct) were taken simultaneously at short intervals from 20
      min before until 10 min after the hypoxic period. Heart rate, arterial oxygen
      saturation (SaO(2)) and respiration rate were recorded continuously. During
      hypoxia, a reduction in SaO(2) by 34% (P < 0.01) was accompanied by an 18%
      reduction in spleen volume and a 2.1% increase in both Hb and Hct (P < 0.05).
      Heart rate increased 28% above baseline (P < 0.05). Within 3 min after hypoxia
      SaO(2) had returned to pre-hypoxic levels, and spleen volume, Hb and Hct had all
      returned to pre-hypoxic levels within 10 min. Respiratory rate remained stable
      throughout the protocol. This study of short-term exposure to eupneic normobaric
      hypoxia suggests that hypoxia plays a key role in triggering spleen contraction
      and subsequent release of stored erythrocytes in humans. This response could be
      beneficial during early altitude acclimatization.

PMID- 18043934
TI  - Effects of anabolic androgenic steroids on sleep patterns of individuals
      practicing resistance exercise.
AB  - Anabolic androgenic steroid (AAS) abuse has become a public health problem in
      many countries, and is associated with many psychiatric disorders.
      Epidemiological studies have also found increasing numbers of sleep disorders
      reported by individuals using AASs. The purpose of this study was to evaluate
      sleep patterns and disorders in anabolic androgenic users who practice resistance
      exercise. The sample comprised 58 males divided into three groups: (1) 20 current
      AAS users aged 26 +/- 1.2, (2) 21 controls with no history of AAS use, aged 26 +/
      1 and (3) 17 sedentary men with no sleep disorders aged 27.2 +/- 0.34. The
      volunteers spent a night in the sleep laboratory for polysomnography. Comparing
      the three groups, the user group showed reduced sleep efficiency and more wakings
      after sleep onset than the sedentary group (P = 0.001). The sedentary group
      showed a higher percentage of stage 4 than the non-users group. We suggest that
      using of anabolic steroids reduced sleep efficiency and alters sleep
      architecture.

PMID- 18043936
TI  - Evaluation of a cycling pre-load time trial protocol in recreationally active
      humans.
AB  - The need for greater sensitivity in exercise performance measures is of
      particular importance in nutritional intervention studies and such measures have
      been investigated in trained cyclists, but not in those who have no experience of
      laboratory testing and/or the need to pace their effort. The aim of the present
      study was to evaluate a mixed design approach (constant load then time-trial)
      endurance type cycle ergometer protocol using recreationally active participants
      not well accustomed to cycling. Seven participants including one female (age 25
      +/- 5 years; body mass 74.4 +/- 9.3 kg; peak VO(2) 3.91 +/- 0.96 l) completed
      four repeat cycle tests. The test consisted of a "pre-load" (60 min at 65% of
      peak VO(2)) followed by a 20 min time trial (performance measure). Reliability
      for the performance measure was assessed by calculating the individual
      participant coefficient of variation (CV) and a mean CV for the group. Excluding
      a familiarisation trial, mean CV for the group was 3.4% (95% confidence interval
      between 2.0 and 10.1%). It is concluded that the performance test described can
      be used in recreationally active young adults with lower variation after one
      familiarisation trial. The protocol might be used to evaluate an intervention if
      changes in performance are expected to be greater than 3.4%, or greater than
      around 7% if a signal to noise ratio of 2: 1 was to be considered appropriate.

PMID- 18043935
TI  - Changes in the haemostatic system after thermoneutral and hyperthermic water
      immersion.
AB  - Warm water bathing is a popular recreational activity and is frequently used in
      rehabilitation medicine. Although well tolerated in most cases, there are reports
      indicating an increased risk of thrombotic events after hot tub bathing. The
      effects of a 45 min thermoneutral bath followed by a 50 min bath with increasing
      water temperature (maximum 41 degrees C) until reaching a body core temperature
      of 39 degrees C on factors of blood coagulation and fibrinolysis were studied in
      eight healthy male volunteers. Blood was obtained after a 45-min resting period
      as control and after the thermoneutral and hyperthermic bath as well as after
      another 45 min recovery period at the end of the study. Hyperthermic immersion
      (HI) lead to a shortening of activated partial thromboplastin time (aPTT) (P <
      0.05). Fibrinogen concentration decreased immediately after HI (P < 0.05) but
      increased during recovery (P < 0.05). Plasminogen activator inhibitor (PAI)
      activity decreased during HI (P < 0.05), D-dimer concentration was not found to
      change. Thrombocyte count increased (P < 0.05) during HI. The increases in tissue
      type plasminogen activator concentration as well as leucocyte count during HI
      were due to haemoconcentration. Prothrombin time, PAI-activity and granulocyte
      count decreased during thermoneutral immersion (P < 0.05). Warm water bathing
      leads to haemoconcentration and minimal activation of coagulation. The PAI-1
      activity is decreased. A marked risk for thrombotic or bleeding complications
      during warm water bathing in healthy males could not be ascertained.

PMID- 18043937
TI  - Liver transplantation as curative approach for advanced hepatocellular carcinoma:
      is it justified?
AB  - BACKGROUND: Liver transplantation is considered as one of therapeutic approaches
      to hepatocellular carcinoma (HCC). The present study aims to evaluate the
      efficacy of various therapeutic options for HCC. MATERIALS AND METHODS: One
      hundred twenty patients with known HCC in various tumour stages were evaluated in
      the present study. Patients were treated either with primary tumour resection,
      transarterial chemoembolisation (TACE) or liver transplantation (LTx) by an
      interdisciplinary team. RESULTS: The overall 1-year and 5-year survivals of
      patients in LTx group were 95 and 57%, respectively, which were significantly
      higher than those in primary tumour resection group (65 and 33%, P < 0.01) and
      those in TACE group (44 and 4%, P < 0.01). In parallel, 1-year and 5-year tumour
      free survivals of patients in LTx group (75 and 62%) were significantly higher
      than those in primary tumour resection group (50 and 11%, P < 0.01). There were
      no significant differences in 1- and 5-year survivals of patients with early
      tumour stage received LTx or primary tumour resection, whereas patients in
      advanced tumour stage based on pathological findings of explanted liver
      significantly benefited from LTx as compared to primary resection. CONCLUSIONS:
      LTx can be a curative approach for patients with advanced HCC without
      extrahepatic metastasis. However, organ shortage is a major limiting factor in
      the selection of HCC patients for LTx.

PMID- 18043938
TI  - Hepatobiliary resection with inferior vena cava resection and reconstruction
      using an autologous patch graft for intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: In patients with advanced cholangiocarcinoma involving the inferior
      vena cava (IVC), an extended hepatobiliary resection with combined resection and
      reconstruction of the IVC is often prerequisite to obtain a clear resection
      margin. MATERIALS AND METHODS: We present our approach to repair of approximately
      half of a cross-sectional wall defect of the IVC using an autologous external
      iliac venous patch graft during extended hepatobiliary resection with a total
      hepatic vascular exclusion technique. The harvested external iliac vein graft was
      incised longitudinally and trimmed to fit the IVC defect. After multiple stay
      sutures, a continuous running suture using 4-0 prolene was made. RESULTS: Two
      patients who underwent this complex surgery survive 20 and 27 months after
      surgery, respectively. Morbidity of transient edema of the ipsilateral lower leg
      potentially related to graft harvesting was noted in one patient after surgery.
      CONCLUSIONS: The external iliac vein patch graft for IVC resection and
      reconstruction during hepatobiliary resection is technically simple, produces no
      stenosis or caliber change in the reconstructed IVC, and is applicable for at
      least half or less of a cross-sectional defect of the IVC wall to be
      reconstructed.

PMID- 18043940
TI  - Organization of the mycobacterial cell wall: a nanoscale view.
AB  - The biosynthesis of the Mycobacterium tuberculosis cell wall is targeted by some
      of the most powerful antituberculous drugs. To date, the molecular mechanisms by
      which these antibiotics affect the cell wall characteristics are not well
      understood. Here, we used atomic force microscopy - in three different modes - to
      probe the nanoscale surface properties of live mycobacteria and their
      modifications upon incubation with four antimycobacterial drugs: isoniazid,
      ethionamide, ethambutol, and streptomycine. Topographic imaging, combined with
      quantitative surface roughness analysis, demonstrated that all drugs induce a
      substantial increase of surface roughness to an extent that correlates with the
      localization of the target (i.e., synthesis of mycolic acids, arabinogalactans,
      or proteins). Chemical force microscopy with hydrophobic tips revealed that the
      structural alterations induced by isoniazid and ethambutol were correlated with a
      dramatic decrease of cell surface hydrophobicity, reflecting the removal of the
      outermost mycolic acid layer. Consistent with this finding, tapping mode imaging,
      combined with immunogold labeling, showed that the two drugs lead to the massive
      exposure of hydrophilic lipoarabinomannans at the surface. Taken together, these
      structural, chemical, and immunological data provide novel insight into the
      action mode of antimycobacterial drugs, as well as into the spatial organization
      of the mycobacterial cell wall.

PMID- 18043939
TI  - Test of blockers of AQP1 water permeability by a high-resolution method: no
      effects of tetraethylammonium ions or acetazolamide.
AB  - The effects of putative water channel blockers were tested on AQP1-expressing
      Xenopus laevis oocytes by a fast optical method with a time resolution of 1 s and
      a volume resolution of 20 pl. The oocytes were exposed to external hyposmolarity
      and the osmotic water permeability (Lp) derived from the initial 10 s of volume
      change. For longer durations, the effective osmotic gradient across the membrane
      was reduced significantly because of dilution of the intracellular contents and
      of ion transport across the membrane. The latter was monitored by voltage clamp
      of the oocytes. In contrast to previous reports based on slower and less
      sensitive assays, we found no effects of tetraethylammonium ions (TEA+) and
      acetazolamide on Lp. We have no single explanation for this, but several factors
      are considered: (a) If the osmotic gradient is assumed to be constant for periods
      longer than 10 s, the Lp will be underestimated. (b) Hyposmotic gradients
      implemented by dilution with water will entail changes in the ionic strength as
      well; this may enhance loss of salt from the oocyte. (c) By voltage clamping the
      AQP1-expressing oocytes during hyposmotic challenges, we found that TEA+-treated
      oocytes were more electrically leaky than untreated ones. This may obscure
      comparisons between the Lp of treated and untreated oocytes. (d) The nature of
      the ion transport mechanisms in the plasma membrane depends on how oocytes have
      been prepared for experiments and on their viability as indicated by the membrane
      potential. These parameters may vary between laboratories.

PMID- 18043942
TI  - A yeast-based phenotypic screen for aquaporin inhibitors.
AB  - Aquaporins mediate transport of water or small, uncharged solutes across cellular
      membranes according to the prevailing osmotic and chemical gradients. Because of
      their implication in human diseases and pathophysiological states, aquaporins are
      considered as potential drug targets. Yet, specific aquaporin inhibitors for in
      vivo studies are not available. Common functional aquaporin assays that monitor
      biophysical parameters related to volume changes, such as light scattering or
      fluorescence quenching, are time consuming and require costly equipment. Hence,
      they are not well geared for screening large numbers of compounds. In this paper,
      we describe a less demanding phenotypic yeast-based assay on 96-well microplates.
      The assay uses a methylamine-sensitive yeast strain in which a methylamine
      permeable test aquaporin is expressed to rescue proliferation on selection
      plates. Specific inhibition of the aquaporin directly correlates to reduced cell
      proliferation.

PMID- 18043941
TI  - H2O 2-stimulated Ca2+ influx via TRPM2 is not the sole determinant of subsequent
      cell death.
AB  - Activation of transient receptor potential melastatin 2 (TRPM2), a non-selective,
      Ca(2+)-permeable cation channel, is implicated in cell death. Channel opening is
      stimulated by oxidative stress, a feature of numerous disease states. The wide
      expression profile of TRPM2 renders it a potentially significant therapeutic
      target in a variety of pathological settings including cardiovascular and
      neurodegenerative diseases. HEK293 cells transfected with human TRPM2
      (HEK293/hTRPM2) were more vulnerable to H(2)O(2)-mediated cell death than
      untransfected controls in which H(2)O(2)-stimulated Ca(2+) influx was absent.
      Flufenamic acid partially reduced Ca(2+) influx in response to H(2)O(2) but had
      no effect on viability. N-(p-Amylcinnamoyl) anthranilic acid substantially
      attenuated Ca(2+) influx but did not alter viability. Poly(adenosine diphosphate
      ribose) polymerase inhibitors (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N
      dimethylacetamide, 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone
      and nicotinamide) reduced Ca(2+) influx and provided a degree of protection but
      also had some protective effects in untransfected controls. These data suggest
      H(2)O(2) triggers cell death in HEK293/hTRPM2 cells by a mechanism that is in
      part Ca(2+) independent, as blockade of channel opening (evidenced by suppression
      of Ca(2+) influx) did not correlate well with protection from cell death.
      Determining the underlying mechanisms of TRPM2 activation is pertinent in
      elucidating the relevance of this channel as a therapeutic target in
      neurodegenerative diseases and other pathologies associated with Ca(2+)
      dysregulation and oxidative stress.

PMID- 18043943
TI  - Gating of the shaker potassium channel is modulated differentially by N
      glycosylation and sialic acids.
AB  - N-linked glycans, including sialic acids, are integral components of ion channel
      complexes. To determine if N-linked sugars can modulate a rapidly inactivating K+
      channel, the glycosylated Drosophila melanogaster Shaker K+ channel (ShB) and the
      N-glycosylation-deficient mutant (ShNQ), were studied under conditions of full
      and reduced sialylation. Through an apparent electrostatic mechanism, full
      sialylation induced uniform and significant hyperpolarizing shifts in all
      measured voltage-dependent ShB gating parameters compared to those measured under
      conditions of reduced sialylation. Steady-state gating of ShNQ was unaffected by
      changes in sialylation and was nearly identical to that observed for ShB under
      conditions of reduced sialylation, indicating that N-linked sialic acids were
      wholly responsible for the observed effects of sialic acid on ShB gating.
      Interestingly, the rates of transition among channel states and the voltage
      independent rates of activation and inactivation were significantly slower for
      ShNQ compared to ShB. Both effects were independent of sialylation, indicating
      that N-linked sugars other than sialic acids alter ShB gating kinetics but have
      little to no effect on the steady-state distribution of channels among states.
      The effect of sialic acids on channel gating, particularly inactivation gating,
      and the impact of other N-linked sugars on channel gating kinetics are unique to
      the ShB isoform. Thus, ShB gating is modulated by two complementary but distinct
      sugar-dependent mechanisms, (1) an N-linked sialic acid-dependent surface charge
      effect and (2) a sialic acid-independent effect that is consistent with N-linked
      sugars affecting the stability of ShB among its functional states.

PMID- 18043944
TI  - First report of two Balantidium species from the Chinese giant salamander,
      Andrias davidianus: Balantidium sinensis Nie 1935 and Balantidium andianusis n.
      sp.
AB  - Two ciliated protozoa, Balantidium sinensis Nie 1935 and Balantidium andianusi n.
      sp., were isolated from the feces of a wild Chinese giant salamander (Andrias
      davidianus) captured from the mountainous area of Shiyan, Hubei Province, Central
      China in October 2006. It is the first report of Balantidium species inhabiting
      Cryptobranchoidea amphibians. The occurrence of B. sinensis in A. davidianus
      should be a new record because the type specimens were first discovered and named
      by Nie in 1935 from Rana nigromaculata and Rana plancyi. For the lack of enough
      descriptions of taxonomic features in the previous report, it was re-described in
      detail and compared with Nie's type specimens and B. giganteum to complete the
      morphological descriptions in the present work. B. andianusi n. sp. was
      considered to be a new species based on its unique morphological characteristics,
      especially the high length/width ratio of the vestibulum (8:1). Comparisons were
      also made among Balantidium species that were found from urodele amphibians.

PMID- 18043945
TI  - Trichomonas adhere and phagocytose sperm cells: adhesion seems to be a prominent
      stage during interaction.
AB  - Tritrichomonas foetus and Trichomonas vaginalis are extracellular parasites of
      the urogenital tract of cattle and humans, respectively. They cause infertility
      and abortion, but there is no documented information on the susceptibility of
      bovine sperm cells to this cattle parasite. The aim of this present work was to
      study the effects provoked by T. foetus and T. vaginalis when in interaction with
      bovine and human sperm cells. The bovine and human spermatozoa were obtained from
      uninfected bulls and men, respectively, and were exposed to living trichomonads
      over different periods of time. Light microscopy, video microscopy, scanning, and
      transmission electron microscopy first revealed a tropism, then a close proximity
      followed by a tight adhesion between these two different cells. A decrease in the
      spermatozoa motility was observed as well intense semen agglutination. The
      adhesion between trichomonads to the sperm cell occurred either by the flagella
      or sperm head. Motile parasites were observed during the next 12 h, whereas sperm
      cells in contact with the parasites rapidly became immotile. The parasites were
      able to maintain the sperm cells attached to their cell surface, followed by
      phagocytosis. This process began with a tight membrane-membrane adhesion and the
      incorporation of the sperm cell within an intracellular vacuole. Afterwards, the
      sperm cell was gradually digested in lysosomes. Many trichomonads were injured
      and/or died on making contact with the spermatozoa possibly due to necrosis.
      Results from this study demonstrated that both T. foetus and T. vaginalis
      interact with sperm cells provoking damage and death of these reproductive cells.
      Differences in the behavior of both trichomonads were evident, showing that T.
      vaginalis was much more virulent than T. foetus. The possible role of
      trichomonads in reproductive failure is discussed.

PMID- 18043946
TI  - Does attraction to frugivores or defense against pathogens shape fruit pulp
      composition?
AB  - Fruit traits evolve in response to an evolutionary triad between plants, seed
      dispersers, and antagonists that consume fruits but do not disperse seeds. The
      defense trade-off hypothesis predicts that the composition of nutrients and of
      secondary compounds in fruit pulp is shaped by a trade-off between defense
      against antagonists and attraction to seed dispersers. The removal rate model of
      this hypothesis predicts a negative relationship between nutrients and secondary
      compounds, whereas the toxin-titration model predicts a positive relationship. To
      test these alternative models, we evaluated whether the contents of nutrients and
      secondary compounds can be used to predict fruit removal by mutualists and
      pathogens in 14 bird-dispersed plants on a subtropical island in Sao Paulo state,
      southeastern Brazil. We selected eight to ten individuals of each species and
      prevented fruit removal by covering four branches with a net and left fruits on
      four other branches available to both, vertebrate fruit consumers and pathogens.
      The persistence of ripe fruits was drastically different among species for bagged
      and open fruits, and all fruit species persisted longer when protected against
      seed dispersers. We found that those fruits that are quickly removed by
      vertebrates are nutrient-rich, but although the attack rate of pathogens is also
      high, these fruits have low contents of quantitative defenses such as tannins and
      phenols. Thus, we suggest that the fruit removal rate by seed dispersers is the
      primary factor selecting the levels of fruit defense. Likewise, nutrient-poor
      fruits have low removal of seed dispersers and low probability of attack by
      pathogens. These species retain ripe fruits in an intact condition for a
      prolonged period because they are highly defended by secondary compounds, which
      reduce overall attractiveness. However, this strategy might be advantageous for
      plants that depend on rare or unreliable dispersers.

PMID- 18043947
TI  - What parathyroid hormone levels should we aim for in children with stage 5
      chronic kidney disease; what is the evidence?
AB  - The bone disease that occurs as a result of chronic kidney disease (CKD) is not
      only debilitating but also linked to poor growth and cardiovascular disease. It
      is suspected that abnormal bone turnover is the main culprit for these poor
      outcomes. Plasma parathyroid hormone (PTH) levels are used as a surrogate marker
      of bone turnover, and there is a small number of studies in children that have
      attempted to identify the range of PTH levels that correlates with normal bone
      histology. It is clear that high PTH levels are associated with high bone
      turnover, although the range is wide. However, the ability of PTH levels to
      distinguish between low and normal bone turnover is less clear. This is an
      important issue, because current guidelines for calcium and phosphate management
      are based upon there being an "optimum" range for PTH. This editorial takes a
      critical look at the evidence upon which these recommendations are based.

PMID- 18043948
TI  - Exploring the differential experience of breast cancer treatment-related
      symptoms: a cluster analytic approach.
AB  - INTRODUCTION: Cancer patients experience multiple concurrent symptoms. This
      exploratory analysis assessed symptom burden among patients undergoing
      chemotherapy for breast cancer to identify distinct subgroups of patients who
      experience differential symptom burden and assessed whether the patient subgroups
      were associated with deleterious quality of life (QOL) outcomes. MATERIALS AND
      METHODS: Women (N = 133) with stage I and II breast cancer undergoing adjuvant
      chemotherapy after primary surgery were evaluated at baseline and at the end of
      chemotherapy using the Memorial Symptom Assessment Scale (MSAS) and the SF-36 QOL
      questionnaire. Post treatment MSAS symptoms were included in hierarchical cluster
      analysis. Two patient subgroups were identified that corresponded to a high
      symptom prevalence group and a low-symptom group. RESULTS AND DISCUSSION: No
      marked, statistically significant differences were found between groups on
      demographic, symptoms, QOL, or treatment variables at baseline. Patients in the
      high-symptom cluster were more likely to have stage I disease (p < 0.05). The two
      groups of patients showed significant differences in end-of-treatment symptoms
      and QOL scores (p < 0.05). The high-symptom burden group was more likely to
      report greater symptom prevalence and poorer QOL. CONCLUSIONS: Future research
      needs to examine why these differences occur despite similarities in treatment
      and how symptom burden can be reduced for the high-symptom prevalence group.

PMID- 18043950
TI  - Family physicians' perceptions, beliefs, and attitudes regarding information
      sharing with prostate cancer patients throughout the course of the disease.
AB  - OBJECTIVES: This study aimed to describe family physicians' perceptions regarding
      the concerns of men with prostate cancer as well as their beliefs and attitudes
      toward information sharing and decision making with prostate cancer patients
      throughout the course of their disease. MATERIALS AND METHODS: A questionnaire
      (44 items) was mailed to 780 board-certified family physicians registered in the
      2003 computerized database of Clalit Health Services, Israel's largest health
      maintenance organization. RESULTS: Three hundred eighty-two (50%) physicians
      completed the questionnaires. Overall, respondents believed that patients have
      substantial concerns throughout the cancer trajectory and that the most troubling
      issue is the fear of disease progression. There were no significant differences
      in the amount of information physicians were willing to share with patients
      throughout the course of the disease. Sixty-four percent of respondents stated
      that they would tailor the information to the patients' wishes and
      characteristics. Seventy percent felt competent at breaking bad news and 74%
      would discuss emotions with patients. Fifty-five percent of respondents preferred
      that patients be autonomous in their decision making. CONCLUSIONS: Family
      physicians in Israel are aware of patients' concerns and recognize the importance
      of sharing information with prostate cancer patients. Further studies are needed
      to examine the practice of these attitudes and to verify whether they are
      compatible with patients' expectations in the relevant cultural and ethnic
      context.

PMID- 18043951
TI  - Synthesis, in vitro and in vivo characterization of (64)Cu(I) complexes derived
      from hydrophilic tris(hydroxymethyl)phosphane and 1,3,5-triaza-7
      phosphaadamantane ligands.
AB  - Four novel (64)Cu complexes ([(64)Cu(thp)(4)](+) (1), [(64)Cu(TPA)(4)](+) (2),
      [HC(CO(2))(pz(Me2))(2) (64)Cu(thp)(2)] (3) and [HC(CO(2))(tz)(2) (64)Cu(thp)(2)]
      (4), [where thp is tris(hydroxymethyl)phosphine, TPA is 1,3,5-triaza-7
      phosphaadamantane, pz(Me2) is 3,5-dimethylpyrazole and tz is 1,2,4-triazole] were
      successfully synthesized and characterized. The complexes were produced in high
      radiochemical purity and yield (more than 98%) without the need for further
      purification. Their logP values and serum stabilities were measured and in vitro
      behavior was observed in cultured EMT-6 cells. The logP values (+/- standard
      deviation) obtained were -2.26 +/- 0.04 (1), 0.01 +/- 0.01 (2), -1.24 +/- 0.03
      (3) and -2.06 +/- 0.03 (4). Complex 3 demonstrated the highest serum stability,
      with approximately 33% of the complex still intact after 1-h incubation. Complex
      2 showed a rapid cell-association with EMT-6 cells, with more than 8.5%
      association at 2 h. This association was significantly higher (P < 0.001) than
      for the other three compounds after a 2-h incubation (1, 1.21%; 3, 0.63%; 4,
      2.75%). Biodistribution and small-animal positron emission tomography/computed
      tomography was undertaken with 1 in mice bearing EMT-6 tumors. EMT-6 tumor uptake
      was high at 1 h (7.71 +/- 2.17 %ID/g) and decreased slowly over 24 h (4 h, 4.90
      +/- 0.78 %ID/g; 24 h, 3.74 +/- 0.73 %ID/g). The PET/CT images show that the EMT-6
      tumors can be visualized at all time points. In this proof-of-concept study, we
      have successfully synthesized and characterized a novel series of versatile water
      soluble Cu(I) complexes containing monophosphine ligands. We also report the use
      of 1 as a building block for new radiopharmaceuticals, perhaps the first time
      such a method has been used in the production of copper radiopharmaceuticals.

PMID- 18043953
TI  - The societal cost of alcohol consumption: an estimation of the economic and human
      cost including health effects in Sweden, 2002.
AB  - This article estimates the societal cost of alcohol consumption in Sweden in
      2002, as well as the effects on health and quality of life. The estimation
      includes direct costs, indirect costs and intangible costs. Relevant cost-of
      illness methods are applied using the human capital method and prevalence-based
      estimates, as suggested in existing international guidelines, allowing cautious
      comparison with prior studies. The results show that the net cost (i.e. including
      protective effects of alcohol consumption) is 20.3 billion Swedish kronor (SEK)
      and the gross cost (counting only detrimental effects) is 29.4 billion (0.9 and
      1.3% of GDP). Alcohol consumption is estimated to cause a net loss of 121,800
      QALYs. The results are within the range found in prior studies, although at the
      low end. A large number of sensitivity analyses are performed, indicating a
      sensitivity range of 50%.

PMID- 18043952
TI  - Identification of differentially expressed genes associated with cotton fiber
      development in a chromosomal substitution line (CS-B22sh).
AB  - One of the impediments in the genetic improvement of cotton fiber is the paucity
      of information about genes associated with fiber development. Availability of
      chromosome arm substitution line CS-B22sh (chromosome 22 short arm substitution
      from 3-79 (Gossypium barbadense) into a TM-1 (Gossypium hirsutum) background)
      provides a novel opportunity to study fiber-associated genes because previous
      studies revealed this line was associated with some superior fiber quality traits
      compared to TM-1. We used an integrated approach of suppression subtractive
      hybridization (SSH), microarray, and real-time reverse transcription-polymerase
      chain reaction (RT-PCR) technologies to identify the potential genes associated
      with fiber development. Utilizing mRNAs from 15 days post-anthesis (dpa) fibers,
      we constructed a SSH cDNA library with chromosome substitution line CS-B22sh as
      the tester and TM-1 as the driver. The SSH cDNA library was screened using
      microarrays. Microarray analysis showed that 36 genes were differentially
      expressed in CS-B22sh 15-dpa fiber compared to TM-1 as confirmed by real time RT
      PCR. These genes include two beta-tubulins, an actin, a putative kinesin light
      chain, a cellulose synthase, glycosyl hydrolase family 3 protein, pyruvate
      decarboxylase, glycoside hydrolase family 5, GDP-mannose pyrophosphorylase,
      dynamin-like protein, annexin, and a number of genes involved in signal
      transduction, and protein, nucleic acid, and lipid metabolisms. To our knowledge,
      this is the first report on identification of differentially expressed fiber
      associated genes in a cotton chromosomal substitution line.

PMID- 18043954
TI  - Evidence for the role of zinc on the performance of dibenzothiophene
      desulfurization by Gordonia alkanivorans strain 1B.
AB  - Gordonia alkanivorans strain 1B is able to desulfurize dibenzothiophene (DBT) to
      2-hydroxybiphenyl (2-HBP), the final product of the 4S pathway. However, both the
      cell growth and the rate of desulfurization can be largely affected by the
      nutrient composition of the growth medium due to cofactor requirements of many
      enzymes involved in the biochemical pathways. In this work, the effect of several
      metal ions on the growth and DBT desulfurization by G. alkanivorans was studied.
      From all the metal ions tested, only the absence of zinc significantly affected
      the cell growth and the desulfurization rate. By increasing the concentration of
      Zn from 1 to 10 mg L(-1), 2-HBP productivity was improved by 26%. The absence of
      Zn(2+), when sulfate was also used as the only sulfur source, did not cause any
      difference in the bacterial growth. Resting cells grown in the presence of Zn(2+)
      exhibited a 2-HBP specific productivity of 2.29 micromol g(-1) (DCW) h(-1), 7.6
      fold higher than the specific productivity obtained by resting cells grown in the
      absence of Zn(2+) (0.30 micromol g(-1) (DCW) h(-1)). These data suggests that
      zinc might have a key physiological role in the metabolism of DBT
      desulfurization.

PMID- 18043956
TI  - [Erosion of the PSYCH-PV and the future financing of hospitals for psychiatry and
      psychotherapy].

PMID- 18043955
TI  - Autotitration positive airway pressure therapy in patients with obstructive sleep
      apnea who are intolerant of fixed continuous positive airway pressure.
AB  - Compliance with continuous positive airway pressure (CPAP) therapy is one of the
      most difficult management problems for patients with obstructive sleep apnea
      (OSA). We postulated that autotitration positive airway pressure (APAP) may be
      effective in some patients who have an intolerance of fixed CPAP. The study was
      done to estimate how often patients who cannot tolerate fixed CPAP can tolerate
      APAP. We identified 25 patients seen in the Sleep Disorders Center who had been
      treated with fixed CPAP for OSA and were intolerant of CPAP therapy despite
      multiple efforts to improve tolerance. We substituted APAP therapy and measured
      subjective and objective compliance with treatment 1 month later. The primary end
      point was the number of patients who successfully tolerated the use of APAP at
      the end of 30 days, measured objectively by the device's compliance monitor. A
      positive outcome was defined as an average use of APAP that was greater than 3 h
      per night on more than 70% of possible nights. Of the 25 patients (mean age, 68
      years; mean apnea-hypopnea index, 35), 11 were able to tolerate APAP therapy. The
      mean number of hours of use in these responders was 6.2; the mean percentage of
      nights of use among responders was 89%. Determinants of successful APAP use were
      an apnea-hypopnea index (AHI) less than 18, male sex, OSA related to rapid eye
      movement, and a high body mass index. APAP therapy may be an effective option in
      patients who do not tolerate fixed-CPAP therapy.

PMID- 18043957
TI  - Variational study of the constituents of cholesterol stones by laser-induced
      breakdown spectroscopy.
AB  - The major and minor constituents of cholesterol gallstones were investigated by
      Laser-induced breakdown spectroscopy. The elements detected in the center and in
      the shell part were calcium (Ca), carbon (C), copper (Cu), hydrogen (H),
      magnesium (Mg), nitrogen (N), sodium (Na), oxygen (O) and potassium (K), but Cu
      was absent from the surface of the cholesterol gallstones. Our experimental
      results revealed that calcium was a major constituent of cholesterol gallstones.
      Our results also showed that the concentration of Ca, Cu and Mg were large in the
      center in comparison with the shell. Laser-induced breakdown (LIB) spectra of
      both portions of the surface (colored part and discolored part) of the
      cholesterol gallstones were recorded. The concentrations of sodium and potassium
      were higher in the non-pigmented (colored) part than in the pigmented part
      (discolored/pigment), which showed that the deficiency of sodium and potassium
      was playing a key role in the formation of discoloration at the different
      locations on the outer surfaces of the cholesterol gallstones. Thus, laser
      induced breakdown spectroscopy (LIBS) is a suitable technique for the analysis of
      cholesterol gallstones without any sample preparation.

PMID- 18043958
TI  - The age distribution, rates, and types of surgery for stress urinary incontinence
      in the USA.
AB  - The objective of this study was to describe the distribution of stress urinary
      incontinence (SUI) surgery across age groups in the USA in 2003. Patients were
      grouped into four age categories: reproductive, perimenopausal, postmenopausal,
      and elderly. Data from the 2003 National Hospital Discharge Survey and National
      Census were used to estimate surgical rates by age group. In 2003, 129,778 women
      underwent 165,776 surgical procedures for SUI. Of these women, 12.2, 53.0, 30.4,
      and 4.5% belonged to reproductive, perimenopausal, postmenopausal, and elderly
      age groups, respectively. Surgical rates (per 10,000 women) were 4, 17, 19, and 9
      in these age groups, respectively. Complications occurred most frequently in
      reproductive age women. Overall, SUI surgical rates were similar for
      perimenopausal and postmenopausal women and exceeded that in the elderly
      population. The greatest percentage of surgical procedures occurred in
      perimenopausal women. Women at all stages of reproductive life may seek surgical
      treatment for SUI.

PMID- 18043959
TI  - Royal Academy of Medicine in Ireland, Radiology Section Meeting. Abstracts.

PMID- 18043961
TI  - Brachial plexus impingement: an unusual complication of bilateral breast
      augmentation.
AB  - Breast augmentation is one of the most commonly performed aesthetic procedures,
      with many studies documenting the early and long-term complications that might be
      expected. This report describes the case of an active young woman who experienced
      severe pain, particularly with movement. Surgical exploration showed the cause of
      this pain to be impingement of the patient's lower brachial plexus by the mammary
      prosthesis. Such a complication has not, to the authors' knowledge, been reported
      previously.

PMID- 18043962
TI  - Striae distensae after subfascial breast augmentation.
AB  - Striae distensae or stretch marks after breast augmentation are a rare
      complication. To date, 10 cases have been published. In seven of these cases, the
      implant was placed in a subglandular position and in the other three cases,
      placement was submuscular. Two cases of stretch marks in two young nulliparous
      women who underwent subfacial breast augmentation are presented. To the best of
      the authors' knowledge, this is the first report of striae distensae after
      subfascial breast augmentation.

PMID- 18043963
TI  - Fish assemblage responses to forest cover.
AB  - We investigated whether fish assemblage structure in southern Appalachian streams
      differed with historical and contemporary forest cover. We compared fish
      assemblages in 2(nd)-4(th) order streams draining watersheds that had increased
      forest cover between 1950 and 1993 (i.e., reforesting watersheds). We sampled
      fish in 50 m reaches during August 2001 and calculated catch-per-unit-effort
      (CPUE) by taxonomic, distributional, trophic, reproductive, and thermal metrics.
      We assigned streams to reforestation categories based on cluster analysis of
      years 1950 and 1993 near-stream forest cover. The relationship between forest
      cover and assemblage structure was assessed using analysis of variance to
      identify differences in fish CPUE in five forest cover categories. Streams
      contained 23 fish species representing six families, and taxa richness ranged
      from 1 to 13 at 30 stream sites. Streams with relatively low near-stream forest
      cover were different from streams having moderate to high near-stream forest
      cover in 1950 and 1993. Fish assemblages in streams having the lowest amount of
      forest cover (53-75%) were characterized by higher cosmopolitan, brood hider,
      detritivore/herbivore, intermediate habitat breadths, run-pool dweller, and warm
      water tolerant fish CPUE compared to streams with higher riparian forest cover.
      Our results suggest that fish assemblage's structural and functional diversity
      and/or richness may be lower in streams having lower recent or past riparian
      forest cover compared to assemblages in streams having a high degree of near
      stream forest cover.

PMID- 18043964
TI  - Analyzing the impacts of dams on riparian ecosystems: a review of research
      strategies and their relevance to the Snake River through Hells Canyon.
AB  - River damming provides a dominant human impact on river environments worldwide,
      and while local impacts of reservoir flooding are immediate, subsequent
      ecological impacts downstream can be extensive. In this article, we assess seven
      research strategies for analyzing the impacts of dams and river flow regulation
      on riparian ecosystems. These include spatial comparisons of (1) upstream versus
      downstream reaches, (2) progressive downstream patterns, or (3) the dammed river
      versus an adjacent free-flowing or differently regulated river(s). Temporal
      comparisons consider (4) pre- versus post-dam, or (5) sequential post-dam
      conditions. However, spatial comparisons are complicated by the fact that dams
      are not randomly located, and temporal comparisons are commonly limited by sparse
      historic information. As a result, comparative approaches are often correlative
      and vulnerable to confounding factors. To complement these analyses, (6) flow or
      sediment modifications can be implemented to test causal associations. Finally,
      (7) process-based modeling represents a predictive approach incorporating
      hydrogeomorphic processes and their biological consequences. In a case study of
      Hells Canyon, the upstream versus downstream comparison is confounded by a
      dramatic geomorphic transition. Comparison of the multiple reaches below the dams
      should be useful, and the comparison of Snake River with the adjacent free
      flowing Salmon River may provide the strongest spatial comparison. A pre- versus
      post-dam comparison would provide the most direct study approach, but pre-dam
      information is limited to historic reports and archival photographs. We conclude
      that multiple study approaches are essential to provide confident interpretations
      of ecological impacts downstream from dams, and propose a comprehensive study for
      Hells Canyon that integrates multiple research strategies.

PMID- 18043966
TI  - Artificial neural networks: useful aid in diagnosing acute appendicitis.
AB  - BACKGROUND: [corrected] The purpose of the study was to assess the role of
      artificial neural networks (ANNs) in the diagnosis of appendicitis in patients
      presenting with acute right iliac fossa (RIF) pain and comparing its performance
      with the assessment made by experienced clinicians and the Alvarado score.
      METHODS: After training and testing an ANN, data from 60 patients presenting with
      suspected appendicitis over a 6-month period to a teaching hospital was collected
      prospectively. Accuracy of diagnosing appendicitis by the clinician, the Alvarado
      score, and the ANN was compared. RESULTS: The sensitivity, specificity, and
      positive and negative predictive values of the ANN were 100%, 97.2%, 96.0%, and
      100% respectively. The ability of the ANN to exclude accurately the diagnosis of
      appendicitis in patients without true appendicitis was statistically significant
      compared to the clinical performance (p=0.031) and Alvarado score of >or=6
      (p=0.004) and nearly significant compared to the Alvarado score of >or=7
      (p=0.063). CONCLUSIONS: ANNs can be an effective tool for accurately diagnosing
      appendicitis and may reduce unnecessary appendectomies.

PMID- 18043968
TI  - Complete clinical response after preoperative chemoradiation in rectal cancer: is
      a "wait and see" policy justified?
AB  - PURPOSE: A proportion of patients, who receive preoperative chemoradiation for
      locally advanced (T3, T4, NX) rectal cancer achieve a complete clinical response
      and a pathologic complete response in the region of 15 to 30 percent. Support is
      growing in the United Kingdom for the concept of "waiting to see" and not
      proceeding to radical surgery when a complete clinical response is observed. The
      purpose of this review was to use a literature search to assess how often
      complete clinical response is achieved after neoadjuvant chemoradiation, the
      concordance of this finding with pathologic complete response, and to determine
      whether it is feasible to observe patients who achieve complete clinical response
      rather than proceed to surgery. RESULTS: In total, 218 Phase I/II or
      retrospective studies and 28 Phase III trials of preoperative radiotherapy or
      chemoradiation were identified: 96 percent of trials documented the pathologic
      complete response, but only 38 trials presented data on the achievement of a
      complete clinical response/partial clinical response. Only five studies were
      found in which patients with clinically staged T2/T3 tumors were treated with
      radiotherapy/chemoradiation and did not routinely proceed to surgery and also
      reported on the long-term outcome of a "wait and see" policy. DISCUSSION: It
      remains uncertain whether the degree of response to chemoradiation in terms of
      complete clinical response or pathologic complete response is a useful clinical
      end point. Studies that include T3 rectal cancer are associated with high local
      recurrence rates after nonsurgical treatment. Few studies report long-term
      outcome after achievement of a complete clinical response. CONCLUSIONS: The end
      point of complete clinical response is inconsistently defined and seems
      insufficiently robust with only partial concordance with pathologic complete
      response. The rationale of a "wait and see" policy when complete clinical
      response status is achieved relies on retrospective observations, which are
      currently insufficient to support this policy except in patients who are
      recognized to be unfit for or refuse radical surgery.

PMID- 18043969
TI  - The gap in laparoscopic colorectal experience between colon and rectal and
      general surgery residency training programs.
AB  - PURPOSE: In this article, we review the laparoscopic experience of general
      surgery and colorectal residency training programs in the United States during
      the past 5 and 12 years, respectively. The purpose of this study was to determine
      whether an adequate experience was being provided, and at what level of training,
      to safely and effectively perform advanced laparoscopy. METHODS: General Surgery
      Operative Reports from the training years 2000 to 2004 were obtained from the
      Accreditation Council for Graduate Medical Education. Similarly, colorectal
      operative performance logs from the training years 1994 to 2005 were obtained
      from the American Board of Colon and Rectal Surgery. RESULTS: From 2000 to 2004,
      basic and advanced laparoscopic cases (as designated by the Accreditation Council
      for Graduate Medical Education) have increased from 10.1 to 12.2 percent and 2.1
      to 3.7 percent, respectively. Within this period, the number of laparoscopic
      colon cases/resident/career has increased from 1.8 to 4.6. The percentage of
      cases performed laparoscopically increased from 3.9 to 22.5 percent from 1993
      1994 to 2004-2005 training years. From 1993 to 2001, the average number of
      laparoscopic cases/resident increased from 6.3 to 16.1. In 2004, the average
      number of cases/resident increased to 45.3. Of this number, 30 were colon, 9.4
      were rectal, and the remaining 5.9 were miscellaneous colorectal procedures.
      CONCLUSIONS: Learning curves for laparoscopic colectomy are reported in the range
      of 20 to 60 cases. Based on the most recent data reviewed, colon and rectal
      resident experience is tending toward this threshold. Recent general surgery
      graduates may be lacking the appropriate volume to reach proficiency in
      laparoscopic colorectal surgery.

PMID- 18043970
TI  - The lymphatic anatomy of the breast and its implications for sentinel lymph node
      biopsy: a human cadaver study.
AB  - BACKGROUND: Current understanding of the lymphatic system of the breast is
      derived mainly from the work of the anatomist Sappey in the 1850s, with many
      observations made during the development and introduction of breast lymphatic
      mapping and sentinel node biopsy contributing to our knowledge. METHODS: Twenty
      four breasts in 14 fresh human cadavers (5 male, 9 female) were studied. Lymph
      vessels were identified with hydrogen peroxide and injected with a lead oxide
      mixture and radiographed. The specimens were cross sectioned and radiographed to
      provide three dimensional images. Lymph (collecting) vessels were traced from the
      periphery to the first-tier lymph node. RESULTS: Lymph collecting vessels were
      found evenly spaced at the periphery of the anterior upper torso draining
      radially into the axillary lymph nodes. As they reached the breast some passed
      over and some through the breast parenchyma, as revealed in the cross-section
      studies. The pathways showed no significant difference between male and female
      specimens. We found also perforating lymph vessels that coursed beside the
      branches of the internal mammary vessels, draining into the ipsilateral internal
      mammary lymphatics. In some studies one sentinel node in the axilla drained
      almost the entire breast. In most more than one sentinel node was represented.
      CONCLUSION: These anatomical findings are discordant with our current knowledge
      based on previous studies and demand closer examination by clinicians. These
      anatomical studies may help explain the percentage of false-negative sentinel
      node biopsy studies and suggest the peritumoral injection site for accurate
      sentinel lymph node detection.

PMID- 18043971
TI  - Risk factors for lymph node metastasis in undifferentiated early gastric cancer.
AB  - BACKGROUND: Endoscopic surgery has not been accepted as a curative treatment for
      intramucosal undifferentiated early gastric cancer (EGC). The purpose of this
      study was to evaluate the predictive factors of lymph node metastasis and explore
      the possibility of using endoscopic surgery for undifferentiated EGC. METHODS: We
      retrospectively analyzed 646 patients with undifferentiated EGC who had undergone
      gastrectomy with D2 lymphadenectomy from January 2000 to March 2005. We used
      univariate and multivariate analysis to identify clinicopathological features
      that were predictive factors for lymph node metastasis. RESULTS: The incidence of
      lymph node metastasis was 4.2% in intramucosal and 15.9% in submucosal
      undifferentiated EGC. Multivariate analysis revealed that submucosal invasion,
      larger tumor size (greater than 2 cm), and presence of lymphovascular invasion
      (LVI), were significantly associated with lymph node metastasis in patients with
      undifferentiated EGC. Tumor size and LVI were independent risk factors for lymph
      node metastasis in cases of intramucosal EGC. Lymph node metastasis was found in
      only one patient (0.5%) who had neither of the two risk factors for intramucosal
      EGC. CONCLUSION: Complete endoscopic resection may be acceptable as a curative
      treatment for intramucosal undifferentiated EGC when the tumor size is less than
      or equal to 2 cm, and when LVI is absent in the postoperative histological
      examination. Radical gastrectomy should be recommended if LVI or unexpected
      submucosal invasion is present.

PMID- 18043972
TI  - A novel use of botulinum toxin to ameliorate bone cancer pain.

PMID- 18043973
TI  - VEGF expression predicts survival in patients with peritoneal surface metastases
      from mucinous adenocarcinoma of the appendix and colon.
AB  - BACKGROUND: High levels of vascular endothelial growth factor (VEGF) in ovarian
      cancer metastases are associated with a worse prognosis in patients treated with
      chemotherapy. VEGF-directed therapy improves survival for those with metastatic
      colorectal cancer. Patients with mucinous adenocarcinomas metastatic to the
      peritoneal surfaces can be treated with cytoreductive surgery, and both tumor
      grade and cytoreduction status are prognostic. We hypothesized that angiogenic
      indices may be prognostic in patients undergoing cytoreductive surgery for
      mucinous adenocarcinoma of the appendix and colon. METHODS: Cytoreductive cases
      from a 5-year period from the University of Cincinnati peritoneal malignancy
      database were reviewed. CD 34 counts (blood vessels) and VEGF expression was
      evaluated by means of immunohistochemistry on specimens from patients undergoing
      cytoreductive surgery and intraperitoneal hyperthermic perfusion (IPHP) for
      mucinous adenocarcinoma. RESULTS: A total of 26 males and 9 females, with a mean
      age of 50 years, underwent cytoreductive surgery and IPHP for mucinous
      adenocarcinoma of appendiceal (n = 32) or colonic (n = 3) origin. With a mean
      follow-up of 18 months (range 1-63 months), 23 had disease recurrence and 12 were
      alive without recurrence. The mean survival was 19 months (range 1-63 months).
      CD34 counts did not correlate with recurrence or survival; however, average VEGF
      counts correlated with survival (P = 0.017), and, for patients with recurrence,
      this correlation was stronger (P = 0.002). CONCLUSIONS: These results suggest
      that markers of tumor angiogenesis may predict survival in patients with
      peritoneal surface metastases from mucinous adenocarcinoma. These findings
      provoke the hypothesis that antiangiogenic therapies may be effective in patients
      with this devastating disease.

PMID- 18043974
TI  - Origin of cancer stem cells: the role of self-renewal and differentiation.
AB  - BACKGROUND: Self-renewal and differentiation potential is the feature of stem
      cells. Differentiation is usually considered to be a one-way process of
      specialization as cells develop the functions of their ultimate fate and lose
      their immature characteristics, such as self-renewal. Progenitor cells, the
      products of stem cells losing the activity of self-renewal, could differentiate
      to mature cells, which have the feature of differentiation and lose the activity
      of self-renewal. The roles for cancer stem cells have been demonstrated for some
      cancers. However, the origin of the cancer stem cells remains elusive. METHODS:
      This review focuses on current scientific controversies related to the
      establishment of the cancer stem cells--in particular, how self-renewal and
      differentiation block might contribute to the evolution of cancer. RESULTS:
      Cancer stem cells may be caused by transforming mutations occurring in multi
      potential stem cells, tissue-specific stem cells, progenitor cells, mature cells
      and cancer cells. Progenitor cells obtain the self-renewal activity by activating
      the self-renewal-associated genes rather than dedifferentiate to tissue special
      stem cells. The transform multi-potential stem cells gain the differentiation
      feature of special tissue by differentiating to cancer cells. Mature cells and
      cancer cells may dedifferentiate or reprogram to cancer stem cells by genetic and
      / or epigenetic events to gain the self-renewal activity and lose some features
      of differentiation. The cancer-derived stem cells are not the "cause", but the
      "consequence" of carcinogenesis. The genetic program controlling self-renewal and
      differentiation is a key unresolved issue. CONCLUSION: Cancer stem cells may be
      caused by disturbance of self-renewal and differentiation occurring in multi
      potential stem cells, tissue-specific stem cells, progenitor cells, mature cells
      and cancer cells.

PMID- 18043975
TI  - S-classification of sentinel lymph node predicts axillary nonsentinel lymph node
      status in patients with breast cancer.
AB  - BACKGROUND: One-half of breast cancer patients with positive sentinel lymph node
      (SN) have no further metastases in the axillary lymph node basin. The aim of the
      present study was to identify patients with positive SN who are unlikely to have
      further metastases in the axillary lymph node basin, using a new classification
      of SN, namely the S-classification. METHODS: Specimens of positive SN were
      subjected to a pathological review according to the previously published S
      classification. S-stages of positive SN were correlated with the status of
      further metastases in the axillary lymph node basin after axillary lymph node
      dissection (ALND). RESULTS: Of 117 patients who underwent sentinel lymph node
      biopsy, 36 (30.8%) had a positive SN and were subjected to level I and II ALND.
      The occurrence of positive nonsentinel nodes was significantly related to the S
      stage of SN. No patient with stage SI had additional metastases in the
      nonsentinel lymph nodes, while 14.3% of patients with SII stage disease and 60.9%
      of patients with SIII disease had other non-SN that were metastatic. CONCLUSION:
      S-stages of positive SN are highly predictive for axillary nonsentinel node
      status. Especially patients with SI sentinel node metastases appear to be at low
      risk for further nonsentinel node metastases.

PMID- 18043976
TI  - Pseudomyxoma peritonei: clinical pathological and biological prognostic factors
      in patients treated with cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy (HIPEC).
AB  - BACKGROUND: Surgical cytoreduction combined with hyperthermic intraperitoneal
      chemotherapy (HIPEC) has been recently advocated as the standard of care for
      pseudomyxoma peritonei (PMP). We reviewed our 10-year monoinstitutional case
      series to identify selection factors predicting postoperative outcome. METHODS:
      One hundred and four patients with PMP were operated on with the aim of
      performing adequate cytoreduction (residual tumor nodules < or =2.5 mm) and
      closed-abdomen HIPEC with mytomicin-C and cisplatin. Previously, 26 patients had
      systemic chemotherapy. PMP was histologically classified into disseminated
      peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and
      intermediate/discordant group (ID). Immunohistochemical stains were performed for
      cytokeratin (CK)-7, CK-20, CDX-2, MUC-2, MUC-5AC, CD-44s. The significance of 22
      potential clinical, pathological, and biological prognostic variables was
      assessed by multivariate analysis. RESULTS: Adequate cytoreduction was performed
      in 89 patients, suboptimal cytoreduction in six, palliative surgery in nine.
      Operative mortality was 1%. Seventy-eight patients were diagnosed with DPAM, 26
      with PMCA, and none with ID. Median follow-up was 37 months (range, 1-110) for
      the overall series. Five-year overall survival (OS) and progression-free survival
      (PFS) were 78.3% and 31.1%, respectively. At multivariate analysis, adequate
      cytoreduction, no previous systemic chemotherapy, and DPAM correlated to better
      OS and PFS, elevated serum CA19.9 correlated only to better PFS. In most cases,
      CK20, CDX-2, and MUC-2 were diffusely positive, while CK-7, MUC-5AC, and CD44s
      were variably expressed. CK20 expression correlated to prognosis at univariate
      analysis. CONCLUSIONS: Favorable outcome after comprehensive treatment can be
      expected in patients with DPAM, not treated with preoperative systemic
      chemotherapy and amenable to adequate cytoreduction. MUC-2, CK-20, and CD44s
      expression may be related to PMP unique biologic behavior.

PMID- 18043977
TI  - Ductal carcinoma in situ: through a glass, darkly.

PMID- 18043978
TI  - Development of new cancers in patients with DCIS: the M.D. Anderson experience.
AB  - BACKGROUND: The purpose of this study was to describe clinical characteristics
      and outcome of mammographically and clinically detected new cancers in patients
      with previously diagnosed ductal carcinoma in situ (DCIS). METHOD: Our database
      was searched to identify patients with a primary diagnosis of DCIS. Those with
      prior evidence of invasive carcinoma were excluded from the analysis. Cumulative
      incidence of new cancers was estimated according to the method of Gray. Survival
      times were estimated using the Kaplan Meier product limit method. RESULTS: A
      total of 799 patients diagnosed and treated for DCIS were included in the
      analysis. Median age at diagnosis was 54 years (range 22-88 years) and median
      tumor size was 1.4 cm (range 0.2-15 cm). After a median follow-up of 2.9 years,
      45 patients (5.6%) had a second event: 14 (31%) with in-situ and 31 (69%) with
      invasive disease. Median disease-free interval was 3.5 years (range 0.5-20.8
      years). The majority of second events (63%) occurred in the opposite breast (P =
      0.048) and the cumulative incidence at 5 years was 6.6%. Overall survival at 5
      years was 97.4%; that for the second event was 76.1%. For mammography and self
      palpation, respectively, the 5-year survival by method of detection of the second
      event was 63.2% and 100% (P = 0.08 with a 33% power to detect a difference).
      CONCLUSION: Second events following DCIS occurs primarily in the opposite breast
      and have a negative impact on survival.

PMID- 18043979
TI  - Perimembrane Aurora-A expression is a significant prognostic factor in
      correlation with proliferative activity in non-small-cell lung cancer (NSCLC).
AB  - PURPOSE: Aurora-A, also known as STK15/BTAK, is a member of the protein
      serine/threonine kinase family, and experimental studies have revealed that
      Aurora-A plays critical roles in cell mitosis and in carcinogenesis. However, no
      clinical studies on Aurora-A expression in non-small-cell lung cancer (NSCLC)
      have been reported. Thus, the present study was conducted to assess the clinical
      significance of Aurora-A status. EXPERIMENTAL DESIGN: A total of 189 consecutive
      patients with resected pathologic (p-)stage I-IIIA, NSCLC were retrospectively
      reviewed, and immunohistochemical staining was used to detect Aurora-A
      expression. RESULTS: Aurora-A expression was negative in 31 patients (16.4%);
      among Aurora-A positive patients, 124 patients showed pure diffuse cytoplasmic
      Aurora-A expression and the other 34 patients showed perimembrane Aurora-A
      expression. Perimembrane Aurora-A tumors showed the highest proliferative index
      (PI) (mean PIs for negative, diffuse cytoplasmic, and perimembrane tumors: 49.2,
      41.7, and 63.5, respectively; P < .001). Five-year survival rates of Aurora-A
      negative, diffuse cytoplasmic, and perimembrane patients were 67.8%, 66.7%, and
      47.6%, respectively, showing the poorest postoperative survival in perimembrane
      patients (P = .033). Subset analyses revealed that perimembrane Aurora-A
      expression was a significant factor to predict a poor prognosis in squamous cell
      carcinoma patients, not in adenocarcinoma patients. A multivariate analysis
      confirmed that perimembrane Aurora-A expression was an independent and
      significant factor to predict a poor prognosis. CONCLUSIONS: Perimembrane Aurora
      A status was a significant factor to predict a poor prognosis in correlation with
      enhanced proliferative activity in NSCLC.

PMID- 18043980
TI  - The accuracy of clinician perceptions of "usual" blood pressure control.
AB  - BACKGROUND: The term "clinical inertia" is used to describe the failure to manage
      a chronic condition aggressively enough to bring it under control. The underlying
      mechanisms for clinical inertia remain poorly understood. OBJECTIVE: To describe
      one potential mechanism for clinical inertia, seen through the lens of clinician
      responses to a computerized hypertension reminder. DESIGN: Cohort study.
      PARTICIPANTS: A total of 509 hypertensive patients from 2 primary care clinics in
      urban Veterans Health Administration (VA) Medical Centers. All patients had
      elevated blood pressure (BP) values that triggered a computerized reminder. Given
      a set of possible responses to the reminder, clinicians asserted at least once
      for each patient that medication adjustments were unnecessary because the BP was
      "usually well controlled". MEASUREMENTS: Using recent BP values from the
      electronic medical record, we assessed the accuracy of this assertion. RESULTS:
      In most instances (57%), recent BP values were not well controlled, with the
      systolic BP (56%) much more likely to be elevated than the diastolic BP (13%).
      Eighteen percent of recent systolic BP values were 160 mmHg or greater.
      CONCLUSIONS: When clinicians asserted that the BP was "usually well controlled",
      objective evidence frequently suggested otherwise. This observation provides
      insight into one potential mechanism underlying clinical inertia.

PMID- 18043981
TI  - Intimate partner violence exposure and change in women's physical symptoms over
      time.
AB  - OBJECTIVE: To examine the change in women's self-reported physical symptoms over
      2 time points in relation to intimate partner violence (IPV) exposure. DESIGN:
      Prospective interview study of 267 women recruited from 8 health care settings
      and surrounding communities in Metropolitan Boston. METHODS: We created sums of
      somatic symptoms at 2 separate time points (a mean of 9.5 months apart) using
      items from a modified PHQ-15. A measure of symptom change was computed to measure
      the net change in symptoms over time. A negative score indicated reduction in
      total symptoms, or improvement. Exposure to IPV was measured at both time points.
      RESULTS: Women who reported ongoing IPV across both time points experienced an
      increase in their overall physical symptoms compared to women with past abuse (p
      = .0054) and no abuse (p = .0006). In multivariate regression analysis, ongoing
      IPV at both time points was a statistically significant predictor of symptom
      change. This relationship persisted even after controlling for age, race,
      education, depression, self-report of co-morbid illness, and history of child
      abuse and prior sexual assault (p = .0076). CONCLUSIONS: Women exposed to ongoing
      IPV report increased physical symptoms over time. Clinicians should consider the
      possibility of IPV in patients who remain persistently symptomatic over time in
      addition to employing more traditional means of detecting IPV.

PMID- 18043982
TI  - Does physicians' case volume impact inpatient care costs for pneumonia cases?
AB  - BACKGROUND: Increasing physician case volumes are documented to reduce costs and
      improve outcomes for many surgical procedures but not for medical conditions such
      as pneumonia that consume significant health care resources. OBJECTIVE: This
      study explored the association between physicians' inpatient pneumonia case
      volume and cost per discharge. DESIGN: The design was a retrospective, population
      based, cross-sectional study, using National Health Insurance administrative
      claims data. SETTING: The setting was Taiwan. PARTICIPANTS: The participants were
      a universal sample of 270,002 adult, acute pneumonia hospitalizations, during
      2002-2004, excluding transferred cases and readmissions. MEASUREMENTS:
      Hierarchical linear regression modeling was used to examine the association of
      physician's volume (three volume groups, designed to classify patients into
      approximately equal sized groups) with cost, adjusting for hospital random
      effects, case severity, physician demographics and specialty, hospital
      characteristics, and geographic location. RESULTS: Mean cost was NT$2,255 (US$1 =
      NT$33 in 2004) for low-volume physicians (< or =100 cases) and NT$1,707 for high
      volume physicians (> or =316 cases). The adjusted patient costs for low-volume
      physicians were higher (US$264 and US$235 than high- and medium-volume
      physicians, respectively; both P < .001), with no difference between high- and
      medium-volume physicians. High-volume physicians had lower in-hospital mortality
      and 14-day readmission rates than low-volume physicians. CONCLUSIONS: Data
      support an inverse volume-cost relationship for pneumonia care. Decision
      processes and clinical care of high-volume physicians versus low-volume
      physicians should be studied to develop effective care algorithms to improve
      pneumonia outcomes and reduce costs.

PMID- 18043983
TI  - The dilemma of disclosure: patient perspectives on gay and lesbian providers.
AB  - BACKGROUND: Discrimination toward gay and lesbian patients by health care
      providers has been documented. No study has determined if patient behavior would
      change when seeing a gay/lesbian provider. OBJECTIVE: The objective of the study
      was to examine whether a provider's sexual orientation would affect the choice of
      provider, practice, or preference for a chaperone during genital exams. DESIGN:
      The design of the study was an anonymous, cross-sectional survey. PARTICIPANTS:
      The participants were a random national sample of persons 18 years or older
      residing in the USA able to read English. MEASUREMENTS: The measurements were
      self-reported perceptions and chaperone preference based on provider gender and
      sexual orientation. RESULTS: The response rate was 32% (n = 502). Many
      respondents indicated they would change providers upon finding out their provider
      was gay/lesbian (30.4%) or change practices if gay/lesbian providers were
      employed there (35.4%). Female respondents preferred chaperones most with
      heterosexual male providers (adjusted odds ratio [OR] 1.50, 95% confidence
      interval [CI] = 1.15 to 1.95) followed by homosexual male (OR 1.17, 95% CI = 0.93
      to 1.47), lesbian (reference), and heterosexual female providers (OR 0.63, 95% CI
      = 0.51 to 0.77). Male respondents showed an increased preference for chaperones
      with gay/lesbian providers of either gender (OR 1.52, 95%, CI = 1.22 to 1.90, for
      gay male provider, [reference] for lesbian provider) than with either
      heterosexual male (OR 0.36, 95% CI = 0.26 to 0.52) or heterosexual female
      providers (OR 0.39, 95% CI = 0.29 to 0.54). CONCLUSIONS: Patients may change
      providers, practices, or desire for chaperone based on a provider's gender and
      sexual orientation. Although the low response rate may limit generalizability,
      these findings have the potential to impact aspects of practice structure
      including chaperone use and provider-patient relationships.

PMID- 18043984
TI  - Acute myocardial infarction length of stay and hospital mortality are not
      associated with language preference.
AB  - BACKGROUND: Language barriers between patients and providers may influence the
      process and quality of care. OBJECTIVE: To examine the association of language
      preference with length of stay (LOS) and in-hospital mortality for patients
      admitted for acute myocardial infarction (AMI). DESIGN, SETTING, AND
      PARTICIPANTS: Electronic administrative hospital discharge data for all non
      disabled Medicaid beneficiaries age 35 years and older admitted to all acute care
      California hospitals with a diagnosis of AMI between 1994 and 1998. METHODS: We
      used multivariate regression to explore whether observed differences in the
      hospital LOS and in-hospital mortality between non-English preference (NEP) and
      English preference (EP) individuals could be explained by individual and/or
      hospital level factors. We adjusted for patient level characteristics using 24
      covariates from a previously validated prediction model of mortality after
      hospitalization for AMI. RESULTS: Of 12,609 Medicaid patients across 401
      California hospitals, 2,757 (22%) had NEP. NEP was associated with a 3.9%
      increased LOS (95% CI 0.7, 7.1; p = 0.02) in unadjusted analysis and a 3.8%
      increased LOS (95% CI 0.3, 7.3; p = 0.03) after controlling for patient level
      characteristics. Differences in LOS were no longer significant after adjusting
      receipt of cardiac procedure/ surgery (2.8%; 95% CI -0.6, 6.2; p = 0.1) or after
      adjusting for hospital (0.9%; 95% CI -2.5, 4.3; p = 0.6). Non-English language
      preference was associated with lower in-hospital mortality in unadjusted analysis
      (odds ratio [OR] = 0.80; 95% CI 0.69, 0.94; p = 0.005), but was not significant
      after adjusting for patient level characteristics (adjusted OR [AOR] 0.95; 95% CI
      0.78, 1.27; p = 0.6). Adjusting for receipt of cardiac procedure/ surgery (AOR
      0.97; 95% CI 0.79, 1.18; p = 0.7) and hospital (AOR 0.97; 95% CI 0.78; 1.21; p =
      0.8) did not alter this finding. CONCLUSIONS: Language preference is not
      associated with AMI mortality, and the small increase in length of stay
      associated with non-English preference is accounted for by hospital level
      factors. Our results suggest that system level differences are important to
      consider in studies of the effect of language barriers in the health care
      setting.

PMID- 18043985
TI  - Resident perceptions of work hour limitations: has the 80-hour work week doomed
      the 3-year Internal Medicine residency?

PMID- 18043986
TI  - Re: Preoperative nutritional status of patients undergoing Roux-en-Y gastric
      bypass for morbid obesity.

PMID- 18043987
TI  - Surrogate markers of resectability in patients undergoing exploration of
      potentially resectable pancreatic adenocarcinoma.
AB  - Despite extensive preoperative staging, a significant number of pancreatic
      cancers are unresectable at surgical exploration. Patients undergoing pancreatic
      exploration with a view to resection were studied and comparisons are then made
      between those undergoing resection and a bypass procedure to identify surrogate
      markers of unresectability. One hundred thirteen consecutive patients underwent
      pancreatic exploration for head-of-pancreas (HOP) adenocarcinoma with curative
      intent. Fifty-five underwent pancreaticoduodenectomy and 58 underwent a bypass
      procedure. Student's t test, receiver operator characteristics (ROC) and logistic
      regression were used to compare the predictive value of preoperative patient
      variables collected retrospectively. The bypass group had a significantly higher
      median CA19.9 than the resection group (P = 0.003). Platelet count and neutrophil
      lymphocyte ratio (NLR) were also significantly different (P = 0.013 and P =
      0.026, respectively). ROC analysis indicated that age < or =65, platelet count
      >297 x 10(9)/l, CA19.9 < or =473 Ku/l, and CA19.9-bilirubin ratio were predictive
      variables for resectable disease. NLR and CA19.9-bilirubin ratio had specificity
      values of 92.9 and 97.0%, respectively. From logistic regression, a raised CA19.9
      was found to be an independent risk factor for unresectable disease (P = 0.031).
      A significant proportion of patients with HOP adenocarcinoma are understaged
      preoperatively. Preoperative serology including platelet count, NLR, CA19.9, and
      CA19.9-bilirubin ratio may be used as additional discriminators of resectability
      particularly for high-risk patients.

PMID- 18043988
TI  - Acute gastric dilatation, necrosis and perforation complicating restrictive-type
      anorexia nervosa.

PMID- 18043990
TI  - Intussusception after laparoscopic Roux-en-Y gastric bypass.
AB  - Intussusception after open Roux-en-Y gastric bypass procedure (RYGBP) is a rare
      complication. We present a retrospective review of three cases of antegrade
      intussusception occurring after laparoscopic RYGBP. To our knowledge, these are
      the first documented cases of intussusception after laparoscopic RYGBP. We
      describe the clinical presentation and our management of these three cases.
      Furthermore, we believe that the initial clinical presentation, radiographic
      findings, and management of these patients may be different than those patients
      who have undergone an open RYGBP. With increasing popularity of laparoscopic
      RYGBP, we are likely to see more of this entity.

PMID- 18043989
TI  - Postoperative complications have little influence on long-term quality of life in
      Crohn's patients.
AB  - PURPOSE: The purpose of the study was to determine the influence of postoperative
      complications on long-term quality of life in patients after abdominal operations
      for Crohn's disease. MATERIALS AND METHODS: From 1996 to 2002, 305 Crohn's
      patients underwent abdominal surgery, and 66 patients developed postoperative
      complications. Quality of life was studied using a standardized questionnaire and
      four quality of life instruments. Sixty-six Crohn's patients with uneventful
      postoperative course matched for age, and follow-up time served as controls.
      RESULTS: Forty-eight patients (81%) in the complication group (32 major and 16
      minor) and 43 patients (75%) in the control group answered the questionnaire.
      Postoperative follow-up time was 42 (10-94) and 41 months (13-94; median
      (range)). Quality of life was comparable between groups, except on the subscale
      "physical functioning" of the Short-form 36 on which patients with minor and
      major complications showed impaired quality of life compared to controls (67+/-6,
      69+/-4, and 84+/-2%; mean+/-standard error of the mean; both p<0.05 vs controls).
      The incidence of Crohn's disease-related symptoms at follow-up was unaffected by
      complications (minor 63%, major 56% vs controls 70%; both not significant).
      CONCLUSION: Postoperative complications after abdominal operations for Crohn's
      disease do not impair long-term quality of life in general but may affect
      specific dimensions of quality of life like patients' physical function.

PMID- 18043991
TI  - DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary
      artery disease risks and micronucleus frequency.
AB  - Coronary artery disease (CAD) is a multifactorial process that appears to be
      caused by the interaction of environmental risk factors with multiple
      predisposing genes. In this study, we investigated the effects of the XPD
      Lys751Gln and XRCC1 Arg399Gln polymorphisms on the presence and the severity of
      CAD. We also investigated the presence of DNA damage in the peripheral
      lymphocytes of patients with CAD by using the micronucleus (MN) test and the
      effect of XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on this damage. The
      study population consisted of 147 patients with angiographically documented CAD
      and 48 healthy controls. No association between XPD Lys751Gln or XRCC1 Arg399Gln
      polymorphisms and the presence or the severity of CAD was observed. On the other
      hand, a significantly higher frequency of MN was observed in CAD patients
      compared with controls (5.7 +/- 1.9 vs 5.0 +/- 2.1, respectively, P = 0.018). We
      found an elevated frequency of MN in CAD patients with the XPD 751Gln allele
      (Gln/Gln genotype) or the XRCC1 399Gln (Arg/Gln or Gln/Gln genotypes) allele
      compared with the XPD 751Lys (Lys/Lys genotype) allele or XRCC1 399 Arg (Arg /Arg
      genotype) allele, respectively. These preliminary results suggest that XPD
      Lys751Gln and XRCC1 Arg399Gln polymorphisms may not be a significant risk factor
      for developing CAD. In addition, our results indicate that the MN frequency is
      associated with presence, but not severity, of CAD and is related to the XRCC1
      Arg399Gln and XPD Lys751Gln polymorphisms, suggesting an elevated frequency of MN
      in CAD patients with the XPD 751Gln or XRCC1 399Gln alleles.

PMID- 18043992
TI  - Comparison between metalloproteinases-2 and -9 in healthy subjects, diabetics,
      and subjects with acute coronary syndrome.
AB  - We hypothesized that matrix metalloproteinase (MMP)-2, -9, and tissue inhibitor
      metalloproteinase-1, -2 (TIMP-1, -2) would be abnormal in diabetes and in acute
      coronary syndromes (ACS). We measured MMP-2, -9, and TIMP-1, -2 plasma levels in
      healthy subjects (controls), in type 2 diabetic patients, in nondiabetic patients
      with ACS (ACS) and in diabetic patients with ACS (DACS). We enrolled 165
      controls, 181 diabetic patients, 78 ACS, and 46 DACS. We measured also BMI (body
      mass index), HbA(1c) (glycated hemoglobin) FPG (fasting plasma glucosa), FPI
      (fasting plasma insulin), HOMA index (homeostasis model assessment index), SBP
      (systolic blood pressure), DBP (diastolic blood pressure), TC (total
      cholesterol), LDL-C (low density lipoprotein cholesterol), HDL-C (high-density
      lipoprotein cholesterol), Tg (triglycerides), Lp(a) (lipoprotein(a)) PAI-1
      (plasminogen activator inhibitor-1), Hct (homocysteine), Fg (fibrinogen), and hs
      CRP (high-sensitivity C-reactive protein). A significant increase of BMI was
      observed in the diabetic group, in ACS and DACS patients compared to controls. A
      significant increase of SBP and DBP resulted in the diabetic and DACS groups,
      while only SBP improvement was present in ACS patients with respect to controls.
      A decrease in SBP and DBP was observed in the ACS group, while SBP variation was
      present in DACS patients compared to diabetics, and DBP increase was obtained in
      the DACS group with respect to ACS patients. TC, LDL-C, Tg, and Lp(a) increase
      was present in diabetics, while TC, Tg, and Lp(a) improvement was present in ACS
      and DACS patients with a significant decrease of HDL-C levels in diabetic, ACS,
      and DACS groups compared to controls. A decrease in LDL-C was obtained in ACS and
      DACS groups, while HDL-C increase was observed in these patients with respect to
      diabetics. Tg levels were higher in the DACS group compared to diabetics and ACS
      patients, respectively. Increases in PAI-1, Hct, Fg, and hs-CRP were present in
      diabetic and DACS groups, while PAI-1, Hct, and hs-CRP improvement was obtained
      in ACS patients with respect to controls. Higher PAI-1 levels came about in ACS
      and DACS groups, while HCT and Fg levels were lower in ACS patients compared to
      diabetics. An increase in Fg was present in the DACS group with respect to ACS
      patients. A decrease in Hs-CRP was observed in DACS patients compared to
      diabetics and the ACS group, respectively. Higher MMP-2, MMP-9, TIMP-1, and TIMP
      2 levels were present in diabetic, ACS, and DACS patients compared to controls.
      Significant MMP-2, TIMP-1, and TIMP-2 increases were observed in ACS and DACS
      groups, while MMP-9 decreased in these patients compared to diabetics. In
      conclusion, MMP-2, MMP-9, TIMP-1, and TIMP-2 plasma levels were higher in
      diabetic, ACS, and DACS patients, which may reflect abnormal extracellular matrix
      metabolism in diabetes and in acute coronary syndrome.

PMID- 18043993
TI  - Interleukin-18: a strong predictor of the extent of coronary artery disease in
      patients with unstable angina.
AB  - The aim of this study was to confirm that plasma interleukin (IL)-18 level is
      associated with the extent of coronary artery disease in unstable angina
      patients. Previous studies have shown that patients with unstable angina have
      significantly higher plasma IL-18 levels than healthy volunteers. However, the
      association between IL-18 and the extent of coronary artery atherosclerosis in
      patients with unstable angina remains unclear. Plasma concentrations of IL-18 and
      high-sensitivity C-reactive protein (hs-CRP) were measured in 166 consecutive
      patients admitted for coronary arteriography. One hundred and eighteen patients
      with unstable angina had coronary artery disease (coronary artery disease group;
      severity score: 2.32 +/- 1.47; Gensini score: 31.3 +/- 25.9), and 48 patients
      with coronary risk factors and without coronary artery lesions served as the risk
      control group. Plasma levels of IL-18 were higher in the coronary artery disease
      group than in the risk control group (P = 0.062). Additionally, plasma levels of
      IL-18 were significantly higher in 77 coronary artery disease patients with
      severity score > or =2 than in the risk control group (242.3 +/- 110.6 vs 209.8
      +/- 120.3 pg/ml, P = 0.016). By univariate analysis, log-transformed plasma IL-18
      concentration was positively correlated with coronary artery disease severity
      score (r = 0.244, P = 0.009). By multiple regression analyses, the association
      between coronary artery disease severity score and IL-18 remained significant
      (beta = 0.733, P = 0.017) when controlling for age, diabetes mellitus and left
      ventricular ejection fraction. Additionally, coronary artery disease severity
      score was greater in the highest tertile (>246 pg/ml) of plasma IL-18 levels than
      in the middle (176-246 pg/ml) and the lowest (<176 pg/ml) tertiles (2.79 +/- 1.52
      vs 2.05 +/- 1.08 vs 2.13 +/- 1.66, P = 0.028). Of note, plasma hs-CRP level had
      no significant correlation with coronary artery severity. Plasma IL-18 level is
      associated with the extent of coronary artery disease in unstable angina
      patients, suggesting the link between IL-18 and coronary artery atherosclerosis
      in these patients.

PMID- 18043994
TI  - Circulating platelet and neutrophil activation correlates with the clinical
      course of unstable angina.
AB  - Recent studies have suggested important roles of inflammation in the
      pathophysiology of unstable angina (UA). We investigated whether activation of
      the circulating platelets and neutrophils were implicated in inflammatory
      reactions associated with unstable angina Expressions of platelet P-selectin and
      neutrophil CD11b, and neutrophil-platelet aggregates were evaluated by flow
      cytometry in anticoagulated peripheral venous blood from 71 patients with UA and
      22 patients with stable angina (SA). Expressions of platelet P-selectin and
      neutrophil CD11b, and neutrophil-platelet aggregates on the admission day were
      all significantly higher in 71 patients with UA than 22 with SA (median, mean
      fluorescence intensity [MFI]: 7.00 vs 4.51, P < 0.01, 64.68 vs 47.75, P = 0.0007;
      and % of 10 000 neutrophils: 7.84 vs 3.40, P = 0.0001, respectively). These three
      parameters in 43 patients with UA were significantly decreased (MFI: 4.23, P =
      0.003, 50.82, P = 0.0003; and % of 10 000 neutrophils: 5.04, P = 0.0001,
      respectively) 7 days after the first measurement. These results indicate that
      circulating activated platelets and neutrophils are more strongly implicated in
      the acute phase of UA. These findings also suggest that thrombus formation after
      rupture of atherosclerotic plaques as well as plaque formation involves
      inflammatory reactions.

PMID- 18043995
TI  - Impact of anemia on nonfatal coronary events after percutaneous coronary
      interventions.
AB  - Anemia is associated with higher rates of cardiovascular events in patients with
      heart failure, acute myocardial infarction, and in patients undergoing coronary
      artery bypass graft surgery. Although studies have focused on fatal coronary
      events in anemic patients following percutaneous coronary intervention (PCI),
      data is lacking regarding nonfatal coronary events. The aim of our study was to
      analyze the incidence of anemia in patients who developed nonfatal events after
      successful PCI, and to make a comparison with event-free patients. Forty-nine
      consecutive patients with and 51 without nonfatal coronary events (nonfatal
      myocardial infarction, coronary artery bypass grafting, or repeat PCI) during the
      1-year follow-up after the index PCI procedure were included in the study. Anemia
      was defined using World Health Organization (WHO) criteria as a hematocrit value
      at initial presentation <39% for men and <36% for women. Baseline hematocrit
      levels were measured before the procedure. Baseline clinical, lesion, and
      procedural characteristics were comparable in both groups. Anemia was present in
      33.8% of men and 30.4% of women. The incidence of anemia in patients with
      nonfatal coronary events was 46.9% and 15.7% in the event-free group, which was
      significantly different (P = 0.001). Anemia was found to be an independent risk
      factor for nonfatal coronary events in PCI patients (odds ratio: 2.24, 95%
      confidence interval: 1.05-4.79; P = 0.036). In conclusion, anemia is an important
      risk factor for predicting nonfatal coronary events after PCI. Although previous
      studies have shown its impact on fatal events, this study has demonstrated that
      anemia also has a role in nonfatal thrombotic coronary events and restenosis.

PMID- 18043996
TI  - Sinus arrest caused by occlusion of the sinus node artery during percutaneous
      coronary intervention for lesions of the proximal right coronary artery.
AB  - We examined the frequency of side-branch occlusion of the sinus node (SN) artery
      and of the subsequent sinus arrest in 80 consecutive patients who underwent
      percutaneous coronary intervention (PCI) for proximal right coronary artery (RCA)
      lesions. Side-branch occlusion of the SN artery occurred during PCI in 14 (17.5%)
      patients. Sinus arrest with junctional escape rhythm developed in 4 (28.6%) of
      these 14 patients. Temporary ventricular pacing was performed for one patient.
      The junctional escape rhythm disappeared in all of the patients within 3 days of
      the SN artery occlusion. The frequency of a single blood supply to the SN by the
      SN artery originating from the RCA did not differ significantly between the
      patients with and without sinus arrest (4/4 [100%]) vs 9/10 [90%]). In
      conclusion, although side-branch occlusion of the SN artery often occurs during
      PCI for proximal RCA lesions, where the SN artery originated, it does not always
      produce sinus arrest even in cases of a single blood supply to the SN by the SN
      artery originating from the RCA. Even though sinus arrest is caused by the
      occlusion of the SN artery, this bradyarrhythmia seems to disappear in the short
      term.

PMID- 18043997
TI  - The echocardiographic Tei-index reflects early myocardial damage induced by
      anthracyclines in patients with hematological malignancies.
AB  - Anthracyclines are antineoplastic agents that are effective against solid tumors
      and hematological malignancies. However, drug-induced cardiotoxicity imposes dose
      limitations. Myocardial damage due to anthracyclines has been assessed by
      measuring left ventricular ejection fraction (LVEF) or fraction shortening (FS)
      by echocardiography and criteria for discontinuing treatment have been
      established based on these indexes. However, cardiotoxicity is already
      irreversible when either LVEF or FS fulfills these criteria. The Tei-index has
      recently been established to assess combined systolic and diastolic myocardial
      function during echocardiography. It can also detect small changes in cardiac
      function. We therefore surmised that the Tei-index would reflect early myocardial
      damage induced by anthracyclines. We treated 23 patients with the anthracycline,
      doxorubicin (DXR), and examined them at least twice during the treatment. An
      additional dose of DXR significantly correlated with a change in the Tei-index
      (DeltaTei-index). In contrast, a change in LVEF did not correlate with increased
      doses of DXR. The DeltaTei-index did not correlate with either LVEF or the Tei
      index before treatment. These results suggested that the DeltaTei-index is a more
      sensitive indicator of early cardiotoxicity induced by anthracyclines than LVEF
      regardless of its value before treatment.

PMID- 18043998
TI  - Plasma brain natriuretic peptide and systemic ventricular function in
      asymptomatic patients late after the Fontan procedure.
AB  - While increased plasma brain natriuretic peptide (BNP) levels have been
      documented late after the Fontan procedure, its significance remains unclear. We
      sought to test the hypothesis that plasma BNP levels reflect systemic ventricular
      function after the Fontan procedure by interrogating the relationship between
      plasma BNP level and indices of ventricular function. The plasma BNP levels and
      systemic ventricular function, as determined by conventional and tissue Doppler
      assessments, acoustic quantification (AQ), and myocardial performance index
      (MPI), of 35 asymptomatic Fontan patients were compared to those of 34 control
      subjects who had previous repair of ventricular septal defect. When compared with
      controls, Fontan patients had significantly higher plasma BNP levels (median 21
      pg/ml, range 5-397 vs median 15 pg/ml, range 5-62, P = 0.04). Their systolic and
      diastolic ventricular function was impaired as evidenced by reduced systemic
      ventricular early diastolic (E) inflow velocity, early to late (A) diastolic
      inflow velocity ratio, left and right annular early diastolic (e), late diastolic
      (a), and systolic (s) velocities, AQ-derived ventricular fractional area change,
      peak emptying rate, and peak filling rate, and increased AQ-derived atrial
      filling fraction and MPI (all P < 0.05). Plasma BNP levels correlated negatively
      with E and A velocities, left-sided annular a velocity, and right-sided annular
      e, a, and s velocities, and positively with AQ-derived atrial filling fraction
      (all P < 0.05). In conclusion, our findings suggest that plasma BNP levels
      reflect primarily the diastolic function of the systemic ventricle in
      asymptomatic Fontan patients.

PMID- 18043999
TI  - Influence of cilnidipine or nisoldipine on sympathetic activity in healthy male
      subjects.
AB  - The aim of this study was to investigate whether cilnidipine, an N- and L-type
      calcium channel blocker, and nisoldipine, an L-type calcium channel blocker, have
      different effects on sympathetic activity, using an identical group of healthy
      male subjects. Eight healthy men (22-28 years) were given 10 mg of cilnidipine or
      10 mg of nisoldipine in a randomized crossover design. In each trial, in subjects
      without medication on day 1 (control) and with medication on day 2, we measured
      heart rate (HR), low frequency (LF)/high frequency (HF) of HR variability, and
      plasma noradrenaline (NA) in a resting supine position and during head-up tilt,
      and palmar sweating during a mental arithmetic test, before and at 1, 2, 4, 6,
      and 8 h after administration. Time-plasma concentration profiles of the two drugs
      were similar. Measurements in controls on the two days showed no significant
      difference in any of these parameters. Nisoldipine, but not cilnidipine, slightly
      increased HR and LF/HF at rest. Head-up tilt increased HR, LF/HF, and plasma NA.
      As evaluated with repeated-measures analysis of variance, head-up tilt induced a
      significant increase in LF/HF, but not HR or plasma NA, and the effect of
      cilnidipine was significantly less than that of nisoldipine (P = 0.017). Postural
      hypotension was not observed. There was no difference in mental arithmetic
      induced sweating between the two drugs. Cilnidipine, but not nisoldipine, might
      have a weak inhibitory effect on reflex sympathetic activity.

PMID- 18044000
TI  - Relationship between blood pressure obtained from the upper arm with a cuff-type
      sphygmomanometer and central blood pressure measured with a catheter-tipped
      micromanometer.
AB  - Recently, the importance of central blood pressure for cardiovascular risk
      stratification has been emphasized. Accordingly, the differences in peak systolic
      and bottom diastolic pressures between the ascending aorta and the brachial
      artery should be clarified. Study subjects consisted of 82 consecutive patients
      with suspected coronary artery disease who underwent cardiac catheterization, and
      in whom ascending aortic pressure waveform was obtained using a catheter-tipped
      micromanometer, and at the same time systolic and diastolic pressures were
      measured (single measurement) from the right upper arm with a cuff-type
      sphygmomanometer based on the oscillometric technique. No significant systematic
      difference (bias) was found between the peak pressure obtained in the ascending
      aorta and the systolic pressure from the right upper arm (133.6 +/- 25.1 vs 131.8
      +/- 21.5 mmHg, not significant). Bland-Altman analysis showed only a small bias
      of +1.8 mmHg, and the limits of agreement were 25.4 mmHg and -21.8 mmHg. In
      contrast, the bottom pressure in the ascending aorta was significantly lower
      compared with the diastolic pressure from the upper arm (68.5 +/- 10.7 vs 73.0 +/
      12.4 mmHg, P < 0.0001). Bland-Altman analysis showed a small but significant
      bias of -4.5 mmHg, and the limits of agreement were 14.1 mmHg and -23.1 mmHg. The
      observed biases seemed to remain within practical range. However, random
      variation in the two measurements was rather large. This is considered to be
      caused by the random error in the single measurement with the cuff-type
      sphygmomanometer.

PMID- 18044001
TI  - Enhanced expression of TLR4 in smooth muscle cells in human atherosclerotic
      coronary arteries.
AB  - Toll-like receptors (TLRs) play an essential role in innate immunity as
      components of the primary defense system against microbial infections. It has
      become evident that TLRs are also involved in the pathogenesis of various
      cardiovascular diseases. However, the expression patterns of TLRs in the human
      coronary arteries of coronary artery disease (CAD) patients and the regulatory
      mechanisms of their expression remain unknown. The TLR4 expression patterns were
      invstigated by immunohistochemical analysis of coronary specimens obtained from
      autopsy cases or CAD patients by using directional coronary atherectomy. In
      atherosclerotic coronary arteries (n = 8), TLR4 immunoreactivity was colocalized
      with infiltrating inflammatory cells. Interestingly, vascular smooth muscle cells
      of atherosclerotic coronary arteries intensely expressed TLR4 even in the regions
      that had few inflammatory cells. In contrast, TLR4 expression was barely detected
      in the vascular smooth muscle cells of nonatherosclerotic coronary arteries (n =
      4). Furthermore, intense expression of smooth muscle TLR4 was observed in the
      coronary arteries of CAD patients (n = 52). Stimulation with tumor necrosis
      factor alpha and angiotensin II increased the expression of TLR4 mRNA in cultured
      human vascular smooth muscle cells. Candesartan, an antagonist of the angiotensin
      II type 1 receptor (AT1), and N-acetylcystine inhibited angiotensin II-induced
      TLR4 mRNA expression in these cells. These findings suggest that the vascular
      smooth muscle cells of atherosclerotic coronary arteries may be activated to
      express TLR4. Furthermore, proinflammatory cytokines and oxidative stress in the
      inflammatory lesions might contribute to the enhanced expression of TLR4 in
      vascular smooth muscle cells of atherosclerotic arteries.

PMID- 18044003
TI  - Cardiac imaging in a symptomatic patient with multiple coronary artery-left
      ventricular microfistulae.
AB  - We present the case of a 44-year-old woman with acute coronary syndrome and
      multiple coronary artery-left ventricular microfistulae at angiography. To
      evaluate the clinical significance of this observation and to obtain further
      insights into this rare disease, the patient was further examined with
      echocardiography and both magnetic resonance imaging and single-photon emission
      computed tomography, which showed considerable abnormalities.

PMID- 18044002
TI  - Shear stress inhibition of H(2)O(2) induced p66(Shc) phosphorylation by ASK1-JNK
      inactivation in endothelium.
AB  - Shear stress protects endothelium from a variety of risk factors for vascular
      disease. Here, we demonstrate a novel mechanism whereby shear stress inhibited
      reactive oxygen species (ROS)-triggered signaling cascades in endothelial cells.
      Stimulation of bovine aortic endothelial cells (BAECs) with H(2)O(2) induced a
      3.07-fold increase in p66(Shc) phosphorylation. This response was fully blocked
      by pretreatment of cells with specific JNK but not p38 or ERK MAP kinase
      inhibitor. Further study showed that knocking down of apoptosis signal-regulating
      kinase 1 (ASK1) by siRNA transfection in cells dramatically inhibited
      phosphorylation of JNK and p66(Shc) elicited by H(2)O(2). Pre-perfusion of BAECs
      cultured in silastic tubes with laminar flow generated by a servo-pump system for
      30 min also significantly suppressed H(2)O(2)-induced phosphorylation of
      p66(Shc). This was accompanied by quantitatively similar inhibition of ASK1 and
      JNK phosphorylation and activation. These results suggested that shear stress
      protects endothelium against oxidant stress by suppression of ASK1-JNK-mediated
      p66(Shc) phosphorylation.

PMID- 18044004
TI  - Cattle ticks of the genera Rhipicephalus and Amblyomma of economic importance in
      Tanzania: distribution assessed with GIS based on an extensive field survey.
AB  - In order to implement a robust integrated tick and tick-borne disease control
      programme in Tanzania, based on ecological and epidemiological knowledge of ticks
      and their associated diseases, a national tick and sero-surveillance study was
      carried out in all 21 regions of the mainland, as well as on Mafia Island,
      between 1998 and 2001. The current distributions of Rhipicephalus appendiculatus,
      R. pravus, Amblyomma variegatum, A. gemma, and A. lepidum are illustrated and
      discussed. Tick distribution maps were assessed using the Weights-of-Evidence
      method (WofE), and employing temperature, humidity, NDVI, rainfall, and land
      cover predictive data. Ground-truthing was done to check correspondence both of
      the data employed in prediction with land-cover characteristics discerned in the
      field as well as of the surveyed and predicted tick distributions. Statistical
      methods were used to analyse associations of the tick species with their
      environment, cattle density, and other ticks. Except for R. appendiculatus, no
      appreciable changes were demonstrated in the predicted and observed tick
      distributions compared to the existing maps that originated in the 1950-1960s.
      Cattle density influenced the distribution of A. variegatum and, to a certain
      extent, of A. lepidum, but had no appreciable influence on the distribution of
      any of the other ticks discussed in this paper, neither did livestock movement.
      Distinct differences for environmental requirements where observed between
      different tick species within the same genus. The predictive maps of R.
      appendiculatus and R. pravus suggest their mutually exclusive distribution in
      Tanzania, and simultaneous statistical analysis showed R. pravus as a greater
      specialist. Of the three Amblyomma species, A. variegatum is the most catholic
      tick species in Tanzania, while both A. gemma and A. lepidum belong to the more
      specialized species. Despite dissimilar habitat preferences, all three Amblyomma
      spp. co-exist in central Tanzania, where very heterogeneous habitats may
      simultaneously satisfy the environmental requirements of all three species. The
      current study, conducted about 4 decades after the last major survey activities,
      has shown that changing livestock policies, unrestricted livestock movement and a
      continuous change in climatic/environmental conditions in Tanzania have brought
      about only limited changes in the distribution patterns of R. appendiculatus, R.
      pravus and the three Amblyomma species investigated. Whether this observation
      indicates a relative indifference of these ticks to environmental and/or climate
      changes allows room for speculation.

PMID- 18044006
TI  - Vertical characterization of soil contamination using multi-way modeling--a case
      study.
AB  - This study describes application of chemometric multi-way modeling approach to
      analyze the dataset pertaining to soils of industrial area with a view to assess
      the soil/sub-soil contamination, accumulation pathways and mobility of
      contaminants in the soil profiles. The three-way (sampling depths, chemical
      variables, sampling sites) dataset on heavy metals in soil samples collected from
      three different sites in an industrial area, up to a depth of 60 m each was
      analyzed using three-way Tucker3 model validated for stability and goodness of
      fit. A two component Tucker3 model, explaining 66.6% of data variance, allowed
      interpretation of the data information in all the three modes. The interpretation
      of core elements revealing interactions among the components of different modes
      (depth, variables, sites) allowed inferring more realistic information about the
      contamination pattern of soils both along the horizontal and vertical
      coordinates, contamination pathways, and mobility of contaminants through soil
      profiles, as compared to the traditional data analysis techniques. It concluded
      that soils at site-1 and site-2 are relatively more contaminated with heavy
      metals of both the natural as well as anthropogenic origins, as compared to the
      soil of site-3. Moreover, the accumulation pathways of metals for upper shallow
      layers and deeper layers of soils in the area were differentiated. The
      information generated would be helpful in developing strategies for remediation
      of the contaminated soils for reducing the subsequent risk of ground-water
      contamination in the study region.

PMID- 18044005
TI  - Pesticide residues in river Yamuna and its canals in Haryana and Delhi, India.
AB  - Yamuna, a prominent river of India covers an extensive area of 345,843 km(2) from
      Yamunotri glacier through six Indian states. Residues of organochlorine
      pesticides (OCPs) namely, isomers of HCH and endosulfan, DDT and its metabolites,
      aldrin, dieldrin, were analysed in water of river Yamuna along its 346 km stretch
      passing through Haryana-Delhi-Haryana and the canals originating from it. beta
      HCH, p.p'-DDT, p.p'-DDE and p.p'-DDD had maximum traceability in test samples (95
      100%) followed by gamma-HCH, alpha-HCH and o.p'-DDD (60-84%) and o.p'-DDT, delta
      HCH and o.p'-DDE (7-30%) while aldrin, dieldrin, alpha and beta endosulfan
      remained below detection limits (BDL). The concentration of SigmaHCH and SigmaDDT
      at different sites of the river ranged between 12.76-593.49 ng/l (with a mean of
      310.25 ng/l) and 66.17-722.94 ng/l (with a mean of 387.9 ng/l), respectively. In
      canals the values were found between 12.38-571.98 ng/l and 109.12-1572.22 ng/l
      for SigmaHCH and SigmaDDT, respectively. Water of Gurgaon canal and Western
      Yamuna canal contained maximum and minimum concentration, respectively both of
      SigmaHCH and SigmaDDT residues. Sources of these pesticides and suggested
      measures to check pesticide pollution of this major Indian river, keeping in view
      its vital link with life, are discussed in this paper.

PMID- 18044007
TI  - Quality assessment of treated tannery wastewater with special emphasis on
      pathogenic E. coli detection through serotyping.
AB  - The present study was undertaken to assess the quality of treated tannery
      effluent discharged from Common Effluent Treatment Plant (CETP), Unnao, India, to
      various water bodies and agricultural lands. The physico-chemical analyses
      revealed that the effluent was yellowish-brown in colour, having alkaline pH,
      high BOD, COD values and contained large quantities of organic and inorganic
      constituents well above the prescribed standards. The bacteriological quality was
      assessed in terms of the presence of heterotrophs and total as well as faecal
      coliforms. All faecal coliforms were identified as Escherichia coli, of which 50%
      were found pathogenic after serotyping. Most of the serotypes were uropathogenic
      Escherichia coli (UPEC) 04. The potential risks of the contamination of different
      ecosystems situated to the vicinity of such sites are obvious. The observations
      of this investigation indicate that the treated tannery effluent released for
      various purposes is not satisfactory, and is far from optimal in attaining the
      safe limits of disposal.

PMID- 18044008
TI  - Changes in health-related quality of life in patients of self-care vs. in-center
      dialysis during the first year.
AB  - OBJECTIVE: In the Lorraine area (France), dialysis centers propose an educational
      program to improve patient's ability to perform dialysis by themselves. The
      objective was to assess changes in health-related quality of life (HRQoL) during
      the first year of dialysis, comparing independent patients with patients on in
      center dialysis. METHOD: All patients aged between 18 and 70 and having started
      their first dialysis between June 1997 and June 1999 in the Lorraine area were
      included. Socio-demographic, medical data and HRQoL (KDQoL) were assessed for
      each patient at enrollment, at 6 and 12 months. RESULTS: At 12 months, 195
      patients were in dialysis, 147 were non-autonomous, and 48 were autonomous.
      Independent patients were younger, were more often in occupational activity, had
      a lower body mass index and had fewer comorbidities. Several dimensions of the
      HRQoL were significantly higher in autonomous patients at baseline: physical
      functioning (60.4 vs. 50.7) and work status (30.9 vs. 18.4); and at 12 months:
      less burden of kidney disease (51.7 vs. 37.3), fewer effects of kidney disease
      (65.9 vs. 54.0), cognitive function (72.0 vs. 62.7) and role-emotional (53.0 vs.
      34.5). CONCLUSION: These results show improved HRQoL among independent patients.
      Our regional care network may be a particularly useful model for undertaking
      actions motivating the healthcare teams and for enhancing the human resources
      devoted to patient education.

PMID- 18044009
TI  - Collective openness and other recommendations for the promotion of research
      integrity.

PMID- 18044010
TI  - The anti-secretory and anti-ulcer activities of esomeprazole in comparison with
      omeprazole in the stomach of rats and rabbits.
AB  - Proton pump inhibitors (PPIs) are widely used to treat hyperacid secretion and
      stomach ulcers. The study investigated the anti-secretory and anti-ulcer effects
      of esomeprazole, the S-isomer of omeprazole on dimaprit, histamine and dibutyryl
      adenosine 3, 5 cyclic monophosphate (dbcAMP)-evoked gastric acid secretion,
      acidified ethanol (AE) and indomethacin (INDO)-induced haemorrhagic lesions and
      on prostaglandin E2 (PGE2) level in the rat in vivo and rabbit in vitro
      preparations. The effect of omeprazole was also investigated for comparison.
      Dimaprit-induced acid secretion was significantly (P < 0.05) inhibited by both
      PPIs in a dose-dependent manner. In the isolated rabbit gastric glands, both PPIs
      elicited marked reductions in histamine- and dbcAMP-evoked acid secretion with
      similar potency. The lesions induced by either AE or INDO were significantly (P <
      0.05) reduced in the presence of either esomeprazole or omeprazole compared to
      control values. Increasing doses of esomeprazole before AE treatment resulted in
      a marked degree of cytoprotection and an elevation in the concentration of bound
      PGE2 in the stomach tissue homogenate. The results show that esomeprazole and
      omeprazole were equally effective against gastric haemorrhagic lesions induced by
      either AE or INDO and in inhibiting dimaprit-, dbcAMP- and histamine-induced
      gastric acid secretion in the rat and rabbit stomach both in vivo and in vitro.
      The gastro-protective effect of esomeprazole was found to be proportional to the
      bound PGE2 levels in the glandular area of the stomach.

PMID- 18044011
TI  - Competitive protein adsorption to polymer surfaces from human serum.
AB  - Surface modification by "soft" plasma polymerisation to obtain a hydrophilic and
      non-fouling polymer surface has been validated using radioactive labelling.
      Adsorption to unmodified and modified polymer surfaces, from both single protein
      and human serum solutions, has been investigated. By using different
      radioisotopes, albumin and Immunoglobulin G (IgG) adsorption has been monitored
      simultaneously during competitive adsorption processes, which to our knowledge
      has not been reported in the literature before. Results show that albumin and IgG
      adsorption is dependent on adsorption time and on the presence and concentration
      of other proteins in bulk solutions during adsorption. Generally, lower albumin
      and IgG adsorption was observed on the modified and more hydrophilic polymer
      surfaces, but otherwise the modified and unmodified polymer surfaces showed the
      same adsorption characteristics.

PMID- 18044012
TI  - Modeling and simulation of hepatic drug disposition using a physiologically
      based, multi-agent in silico liver.
AB  - PURPOSE: Validate a physiologically based, mechanistic, in silico liver (ISL) for
      studying the hepatic disposition and metabolism of antipyrine, atenolol,
      labetalol, diltiazem, and sucrose administered alone or in combination. MATERIALS
      AND METHODS: Autonomous software objects representing hepatic components such as
      metabolic enzymes, cells, and microarchitectural details were plugged together to
      form a functioning liver analogue. Microarchitecture features were represented
      separately from drug metabolizing functions. Each ISL component interacts
      uniquely with mobile objects. Outflow profiles were recorded and compared to wet
      lab data. A single ISL structure was selected, parameterized, and held constant
      for all compounds. Parameters sensitive to drug-specific physicochemical
      properties were tuned so that ISL outflow profiles matched in situ outflow
      profiles. RESULTS: ISL simulations were validated separately and together against
      in situ data and prior physiologically based pharmacokinetic (PBPK) predictions.
      The consequences of ISL parameter changes on outflow profiles were explored.
      Selected changes altered outflow profiles in ways consistent with knowledge of
      hepatic anatomy and physiology and drug physicochemical properties. CONCLUSIONS:
      A synthetic, agent-oriented in silico liver has been developed and successfully
      validated, enabling us to posit that static and dynamic ISL mechanistic details,
      although abstract, map realistically to hepatic mechanistic details in PBPK
      simulations.

PMID- 18044013
TI  - Na,K-ATPase and the role of alpha isoforms in behavior.
AB  - The Na,K-ATPase is composed of multiple isoforms and the isoform distribution
      varies with the tissue and during development. The alpha1 isoform for example, is
      the major isoform in the kidney and many other tissues, while the alpha2 isoform
      is the predominate one in skeletal muscle. All three isoforms are found in the
      brain although in adult rodent brain, the alpha 3 isoform is located essentially
      in neurons while the alpha2 isoform is found in astrocytes and some limited
      neuronal populations. Interestingly the alpha 4 isoform is found exclusively in
      the mid region of the sperm tail. The distribution of the isoforms of the Na,K
      ATPase has been extensively studied in many tissues and during development. The
      examples cited above provide some indication to the diversity of Na,K-ATPase
      isoform expression. In order to understand the significance of this distribution,
      we have developed animals which lack the alpha1, alpha2, and alpha 3 isoforms. It
      is anticipated that these studies will provide insight into the role that these
      isoforms play in driving various biological processes in specific tissues. Here
      we describe some of our studies which deal with the behavioral aspects of the
      alpha1, alpha2, and alpha 3 deficient mice, particularly those that are
      haploinsufficient in one isoform i.e. lacking one functional gene for the alpha1,
      alpha2, or alpha 3 isoforms. Such studies are important as two human diseases are
      associated with deficiency in the alpha2 and alpha 3 isoforms. These are Familial
      Hemiplegic Migraine type 2 and Rapid-Onset Dystonia Parkinsonism, these diseases
      result from alpha2 and alpha 3 isoform haploinsufficiency, respectively. We find
      that the haploinsufficiency of both alpha2 and alpha 3 isoforms result in
      behavioral defects.

PMID- 18044014
TI  - Mechanism of recurrence after radiofrequency catheter ablation of atrial
      fibrillation guided by complex fractionated atrial electrograms.
AB  - BACKGROUND: A better understanding of the mechanisms of recurrent atrial
      fibrillation (AF) after radiofrequency ablation of complex, fractionated atrial
      electrograms (CFAEs) may be helpful for refining AF ablation strategies. METHODS
      AND RESULTS: Electrogram-guided ablation (EGA) was repeated in 30 consecutive
      patients (mean age = 59 +/- 8 years) for recurrent paroxysmal AF, 10 +/- 4 months
      after the first ablation. During the first procedure, CFAEs were targeted without
      isolating all pulmonary veins (PVs). During repeat ablation, all PVs and the
      superior vena cava (SVC) were mapped with a circular catheter and the left atrium
      was mapped for CFAEs. EGA was performed until AF was rendered noninducible or all
      identified CFAEs were eliminated. During repeat ablation, > or =1 PV tachycardia
      was found in 83 PVs in 29 of the 30 patients (97%). Among these 83 PVs, 63 (76%)
      had not been completely isolated previously. During repeat ablation, drivers
      originating in a PV or PV antrum were identified only after infusion of
      isoproterenol (20 mug/min) in 12 patients (40%). At 9 +/- 4 months of follow-up
      after the repeat ablation procedure, 21 of the 30 patients (70%) were free from
      recurrent AF and flutter without antiarrhythmic drugs. CONCLUSIONS: Recurrence of
      AF after EGA is usually due to PV tachycardias. Therefore, it may be preferable
      to systematically map and isolate all PVs during the first procedure. High-dose
      isoproterenol may be helpful to identify AF drivers.

PMID- 18044015
TI  - The Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure
      (COMPANION) trial in perspective.
AB  - The Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure
      (COMPANION) trial is one of several randomized trials that has demonstrated an
      improvement in morbidity and mortality with biventricular pacemakers and/or
      implantable defibrillators. Although the results of the COMPANION trial overlap
      with other trials investigating cardiac resynchronization therapy (CRT) and
      implantable cardioverter-defibrillators (ICDs), there are several unique aspects
      of the trial that warrant special attention. This review focuses on COMPANION in
      light of other CRT trials, and includes a discussion on the patient population
      enrolled, design challenges of the trial, the cost-effectiveness of CRT and CRT
      D, and results of subanalyses using data collected during the trial.

PMID- 18044016
TI  - Inferring connection proximity in networks of electrically coupled cells by
      subthreshold frequency response analysis.
AB  - Electrical synapses continuously transfer signals bi-directionally from one cell
      to another, directly or indirectly via intermediate cells. Electrical synapses
      are common in many brain structures such as the inferior olive, the subcoeruleus
      nucleus and the neocortex, between neurons and between glial cells. In the
      cortex, interneurons have been shown to be electrically coupled and proposed to
      participate in large, continuous cortical syncytia, as opposed to smaller spatial
      domains of electrically coupled cells. However, to explore the significance of
      these findings it is imperative to map the electrical synaptic microcircuits, in
      analogy with in vitro studies on monosynaptic and disynaptic chemical coupling.
      Since "walking" from cell to cell over large distances with a glass pipette is
      challenging, microinjection of (fluorescent) dyes diffusing through gap-junctions
      remains so far the only method available to decipher such microcircuits even
      though technical limitations exist. Based on circuit theory, we derive analytical
      descriptions of the AC electrical coupling in networks of isopotential cells. We
      then suggest an operative electrophysiological protocol to distinguish between
      direct electrical connections and connections involving one or more intermediate
      cells. This method allows inferring the number of intermediate cells,
      generalizing the conventional coupling coefficient, which provides limited
      information. We validate our method through computer simulations, theoretical and
      numerical methods and electrophysiological paired recordings.

PMID- 18044018
TI  - Brain storm.

PMID- 18044020
TI  - A quest for fun.

PMID- 18044019
TI  - Proceedings of the Inaugural ASTRO/ASCO/AHNS Multidisciplinary Head and Neck
      Cancer Symposium. January 18-20, 2007. Rancho Mirage, California, USA.

PMID- 18044017
TI  - Cytokines: Important for implantation?
AB  - PROBLEM: Cytokines are obviously very important in an established pregnancy, but
      what about human embryo implantation? METHODS: Literature review. RESULTS: We
      first discuss the necessity and limits of animal models, and then review the few
      cytokines which have been demonstrated by knock-out methods to be absolutely
      necessary for embryo implantation using in animal models. We then review what is
      known or discussed about the role of other cytokines as deduced from quantitative
      and/or qualitative dysregulation in animals and in humans. CONCLUSIONS: Cytokines
      are indeed involved in implantation as they are in ongoing pregnancy and
      delivery. Relevance to infertility and recurrent pregnancy loss is discussed.

PMID- 18044022
TI  - Liquid NMR probes: Oh so many choices.

PMID- 18044021
TI  - Electron tomography: a 3D view of the subcellular world.

PMID- 18044023
TI  - Proceedings of the LX Annual Meeting of the Italian Society for Veterinary
      Sciences (SISVET), Palermo, Italy, 2006.

PMID- 18044024
TI  - In response to Point:Counterpoint: "Satellite cell addition is/is not obligatory
      for skeletal muscle hypertrophy".

PMID- 18044025
TI  - Small and thin: the controversy over the fetal origins of adult health.
AB  - Examines the Barker hypothesis that fetal environment and low birth weight are
      related to heart disease later in life.

PMID- 18044026
TI  - [X-ray neurodiagnosis of thalamic tumors].

PMID- 18044027
TI  - Re. From my perspective. The practice of surgery--of medicine in general--seems
      more a business enterprise than a service-dedicated profession.

PMID- 18044028
TI  - Patient education Web site.

PMID- 18044029
TI  - Economics of managed care.

PMID- 18044030
TI  - Economics of medicine.

PMID- 18044031
TI  - Macular degeneration.

PMID- 18044032
TI  - Medicare program; revisions to payment policies under the physician fee schedule,
      and other Part B payment policies for CY 2008; revisions to the payment policies
      of ambulance services under the ambulance fee schedule for CY 2008; and the
      amendment of the e-prescribing exemption for computer generated facsimile
      transmissions. Final rule with comment period.
AB  - This final rule with comment period addresses certain provisions of the Tax
      Relief and Health Care Act of 2006, as well as making other proposed changes to
      Medicare Part B payment policy. We are making these changes to ensure that our
      payment systems are updated to reflect changes in medical practice and the
      relative value of services. This final rule with comment period also discusses
      refinements to resource-based practice expense (PE) relative value units (RVUs);
      geographic practice cost indices (GPCI) changes; malpractice RVUs; requests for
      additions to the list of telehealth services; several coding issues including
      additional codes from the 5-Year Review; payment for covered outpatient drugs and
      biologicals; the competitive acquisition program (CAP); clinical lab fee schedule
      issues; payment for renal dialysis services; performance standards for
      independent diagnostic testing facilities; expiration of the physician scarcity
      area (PSA) bonus payment; conforming and clarifying changes for comprehensive
      outpatient rehabilitation facilities (CORFs); a process for updating the drug
      compendia; physician self referral issues; beneficiary signature for ambulance
      transport services; durable medical equipment (DME) update; the chiropractic
      services demonstration; a Medicare economic index (MEI) data change; technical
      corrections; standards and requirements related to therapy services under
      Medicare Parts A and B; revisions to the ambulance fee schedule; the ambulance
      inflation factor for CY 2008; and amending the e-prescribing exemption for
      computer-generated facsimile transmissions. We are also finalizing the calendar
      year (CY) 2007 interim RVUs and are issuing interim RVUs for new and revised
      procedure codes for CY 2008. As required by the statute, we are announcing that
      the physician fee schedule update for CY 2008 is -10.1 percent, the initial
      estimate for the sustainable growth rate for CY 2008 is -0.1 percent, and the
      conversion factor (CF) for CY 2008 is $34.0682.

PMID- 18044033
TI  - Medicare program: changes to the hospital outpatient prospective payment system
      and CY 2008 payment rates, the ambulatory surgical center payment system and CY
      2008 payment rates, the hospital inpatient prospective payment system and FY 2008
      payment rates; and payments for graduate medical education for affiliated
      teaching hospitals in certain emergency situations Medicare and Medicaid
      programs: hospital conditions of participation; necessary provider designations
      of critical access hospitals. Interim and final rule with comment period.
AB  - This final rule with comment period revises the Medicare hospital outpatient
      prospective payment system to implement applicable statutory requirements and
      changes arising from our continuing experience with this system. We describe the
      changes to the amounts and factors used to determine the payment rates for
      Medicare hospital outpatient services paid under the prospective payment system.
      These changes are applicable to services furnished on or after January 1, 2008.
      In addition, the rule sets forth the applicable relative payment weights and
      amounts for services furnished in ASCs, specific HCPCS codes to which the final
      policies of the ASC payment system apply, and other pertinent rate setting
      information for the CY 2008 ASC payment system. Furthermore, this final rule with
      comment period will make changes to the policies relating to the necessary
      provider designations of critical access hospitals and changes to several of the
      current conditions of participation requirements. The attached document also
      incorporates the changes to the FY 2008 hospital inpatient prospective payment
      system (IPPS) payment rates made as a result of the enactment of the TMA,
      Abstinence Education, and QI Programs Extension Act of 2007, Public Law 110-90.
      In addition, we are changing the provisions in our previously issued FY 2008 IPPS
      final rule and are establishing a new policy, retroactive to October 1, 2007, of
      not applying the documentation and coding adjustment to the FY 2008 hospital
      specific rates for Medicare-dependent, small rural hospitals (MDHs) and sole
      community hospitals (SCHs). In the interim final rule with comment period in this
      document, we are modifying our regulations relating to graduate medical education
      (GME) payments made to teaching hospitals that have Medicare affiliation
      agreements for certain emergency situations.

PMID- 18044034
TI  - Effect of increased body mass index on oocyte and embryo quality in IVF patients.
AB  - Obesity may have an adverse effect on the outcome of IVF/intracytoplasmic sperm
      injection (ICSI) treatment. In this study, the effects of increased body mass
      index (BMI) on oocyte and embryo quality during IVF cycles were studied. A
      retrospective analysis of 426 IVF/ICSI cycles was performed. Cycles were
      classified according to the BMI: normal BMI (19-24.9 kg/m(2)), overweight (25
      29.9 kg/m(2)) and obese (> or = 30 kg/m(2)). Cycles were further stratified based
      on age (group 1, < 35 years; group 2, > or = 35 years). Markers of oocyte quality
      (number of oocytes inseminated and fertilization rate) and embryo quality
      (utilization rate, number of embryos discarded and cryopreserved, and mean embryo
      grade) were examined. In group 1, obesity had a significant adverse effect on the
      mean embryo grade (P = 0.02), the embryo utilization rate (P = 0.01), number of
      embryos discarded (P = 0.007) and cryopreserved (P < 0.05). In group 2, there was
      no difference in markers of embryo quality between the three BMI ranks. Obesity
      did not have any significant effect on markers of oocyte quality or clinical
      pregnancy rates. In conclusion, obesity may adversely affect embryo quality in
      young women (<35 years) undergoing IVF/ICSI, while the oocyte quality is not
      affected.

PMID- 18044035
TI  - [108th French Congress of Surgery, Paris 2-4 October, 2006. Primary
      retroperitoneal sarcoma].

PMID- 18044036
TI  - Tomorrow's professor: objectives as guides to learning.

PMID- 18044037
TI  - Can it work? Three New England states have made bold reforms in how we provide
      health care in America. What can we learn from their lead?

PMID- 18044038
TI  - GAO: improve pandemic prep.

PMID- 18044039
TI  - Detecting epidemic malaria, Uganda.

PMID- 18044040
TI  - Extensively drug-resistant tuberculosis, Italy and Germany.

PMID- 18044041
TI  - Buruli ulcer, Nigeria.

PMID- 18044042
TI  - Acetobacter cibinongensis bacteremia in human.

PMID- 18044043
TI  - Risk for epidemics after natural disasters.

PMID- 18044044
TI  - Recombinant sapovirus gastroenteritis, Japan.

PMID- 18044045
TI  - Salmonella typhimurium in Hihi, New Zealand.

PMID- 18044046
TI  - Travel-related Salmonella agama, Gabon.

PMID- 18044047
TI  - Small anellovirus infections in Korean children.

PMID- 18044048
TI  - Antibodies against Leptospira spp. in captive collared peccaries, Peru.

PMID- 18044049
TI  - High tuberculosis and HIV coinfection rate, Johannesburg.

PMID- 18044050
TI  - Tuberculosis trends, Vietnam.

PMID- 18044051
TI  - Vancomycin-resistant enterococci, Mexico City.

PMID- 18044052
TI  - Disseminated bacillus Calmette-Guerin infection and immunodeficiency.

PMID- 18044053
TI  - Clindamycin-resistant Streptococcus pneumoniae.

PMID- 18044054
TI  - Expanded-spectrum beta-lactamase and plasmid-mediated quinolone resistance.

PMID- 18044055
TI  - Viral load and Crimean-Congo hemorrhagic fever.

PMID- 18044056
TI  - Inactivated whole virus influenza A (H5N1) vaccine.

PMID- 18044057
TI  - Resistance to dihydroartemisinin.

PMID- 18044058
TI  - Reproducibility of exhaled biomarkers in COPD--the road less traveled.

PMID- 18044059
TI  - Active smoking among asthmatic youth--how concerned we need to be.

PMID- 18044060
TI  - Occasional review: influenza in COPD: pathogenesis, prevention, and treatment.
AB  - Influenza viruses cause respiratory tract infections that in patients with
      underlying lung diseases such as chronic obstructive pulmonary disease (COPD) are
      associated with exacerbations and excess morbidity and mortality. Typically,
      influenza B is associated with relatively mild, local outbreaks, whereas
      influenza A is the cause of world-wide pandemics. Upon infection, two antigens
      present on the viral surface, hemagglutinin and neuraminidase result in human
      immunity, but since many subtypes of these antigens exist that vary over time,
      immunity in the population is blunted. Vaccination is advocated in high-risk
      groups including patients with underlying (lung) diseases and in the elderly, and
      needs to be repeated annually with vaccines expected to cover the expected change
      in viral antigenicity. When started early, antiviral drugs, especially
      neuraminidase-inhibitors can be prescribed in adjunct to nonspecific
      interventions in an attempt to shorten disease duration and to prevent
      complications in case of an influenza infection. Currently, the effectiveness of
      antiviral drugs specifically in patients with COPD has not been proven.

PMID- 18044061
TI  - Bronchodilators in COPD: impact of beta-agonists and anticholinergics on severe
      exacerbations and mortality.
AB  - This review summarizes the long-term clinical outcomes associated with beta
      agonist and anticholinergic bronchodilator use in patients with chronic
      obstructive pulmonary disease (COPD). Pooled data from randomized placebo
      controlled trials of at least three months duration were used to evaluate the
      risk for COPD hospitalizations, respiratory mortality, and total mortality. The
      results show that anticholinergic use is associated with a 30% reduction in COPD
      hospitalizations, a 70% reduction in respiratory mortality, and without a
      significant effect on total mortality. In contrast, beta-agonist use had no
      effect on COPD hospitalizations and was associated with a two-fold increased risk
      for respiratory death compared with placebo. When the two bronchodilators were
      directly compared with each other, beta-agonists were associated with a two-fold
      increased risk for COPD hospitalization and a five-fold increased risk for total
      mortality compared with anticholinergics. When beta-agonists were added to either
      anticholinergic use or inhaled corticosteroid use alone, there was no significant
      improvement in any long-term clinical outcome. These results indicate that
      anticholinergics should be the bronchodilator of choice in COPD, while beta
      agonists may be associated with poorer disease control.

PMID- 18044062
TI  - Respiratory muscles training in COPD patients.
AB  - It is known that respiratory muscles undergo adaptation in response to overload
      stimuli during exercise training in stable COPD patients, thus resulting in
      significant increase of respiratory muscle function as well as the individual's
      improvements. The present article reviews the most updated evidence with regard
      to the use of respiratory muscle training (RMT) methods in COPD patients.
      Basically, three types of RMT (resistive training, pressure threshold loading,
      and normocapnic hyperpnea) have been reported. Frequency, duration, and intensity
      of exercise must be carefully considered for a training effect. In contrast with
      the plentitude of existing data inherent to inspiratory muscle training (IMT),
      literature is still lacking in showing clinical and physiological studies related
      to expiratory muscle training (EMT). In particular, while it seems that IMT is
      slightly superior to EMT in providing additional benefits other than respiratory
      muscle function such as a reduction in dyspnea, both the effects and the safety
      of EMT is still to be definitively elucidated in patients with COPD.

PMID- 18044063
TI  - Prulifloxacin: a brief review of its potential in the treatment of acute
      exacerbation of chronic bronchitis.
AB  - Exacerbations of chronic bronchitis (AECB) are a major cause of morbidity and
      mortality in patients with chronic obstructive pulmonary disease (COPD), and
      their impact on public health is increasing. The new fluoroquinolones have an
      excellent spectrum providing cover for the most important respiratory pathogens,
      including atypical and "typical" pathogens. Not surprisingly, different
      guidelines have inserted these agents among the drugs of choice in the empirical
      therapy of AECB. The pharmacokinetic and dynamic properties of the new
      fluoroquinolones have a significant impact on their clinical and bacteriological
      efficacy. They cause a concentration-dependent killing with a sustained post
      antibiotic effect. This review discusses the most recent data on the new
      fluoroquinolone prulifloxacin and critically analyses its activity and safety in
      the management of AECB.

PMID- 18044064
TI  - The development of anticholinergics in the management of COPD.
AB  - Anticholinergics have been used to treat obstructive respiratory disease for many
      years from historical preparations of the deadly nightshade genus, to the more
      recent developments ofipratropium, oxitropium, and tiotropium. The medical
      treatment of airways obstruction has focused on achieving maximal airway function
      through bronchodilators. Of the two main bronchodilators, beta2-agonists are
      often the first treatment choice although there is evidence of equivalence and
      some suggestions of the superiority of anticholinergics in chronic obstructive
      pulmonary disease (COPD). The following review looks at the background of
      anticholinergics, their pharmacological properties, and the evidence for use with
      suggestions for their place in the treatment of COPD.

PMID- 18044065
TI  - Prevention and control of influenza in persons with chronic obstructive pulmonary
      disease.
AB  - Despite recommendations for annual vaccination against influenza, more than half
      of patients with chronic obstructive pulmonary disease (COPD) in developed
      countries do not receive this vaccine. Influenza is characterized by its
      potentially of causing epidemics and by excess morbidity and mortality in
      patients with COPD and other chronic medical conditions. Good evidence of the
      efficacy, effectiveness, and cost-effectiveness of influenza vaccination
      underlines the recommendation of use in patients with COPD. Influenza vaccination
      could reduce influenza-related complications and exacerbations in patients with
      COPD, therefore reducing hospitalizations and deaths. Each year, all persons with
      COPD should be vaccinated with the inactivated trivalent influenza vaccine
      containing the most frequent two influenza A viral strains and one influenza B
      viral strain detected in the influenza season of the previous year. To achieve a
      100% vaccination rate in patients with COPD, all patients with COPD registered in
      health insurance companies and attended in health centers and specialized clinics
      should be vaccinated during the immunization period (October-December). Antiviral
      therapies could be used as an adjunct to vaccination and to reduce influenza
      transmission in outbreaks. Antiviral therapies could reduce the duration and
      complications of influenza when administered within two days of the onset of
      illness. Research is necessary for new antiviral therapies that could prevent
      influenza with cost-effectiveness similar to the influenza vaccine.

PMID- 18044066
TI  - Influenza infection and COPD.
AB  - Influenza is a disease with global impact that causes enormous morbidity and
      mortality on an annual basis. It primarily infects the respiratory tract and
      causes a broad range of illness ranging from symptomless infection to fulminant
      primary viral and secondary bacterial pneumonia. The severity of infection
      depends on both the virus strain and a number of host factors, primarily age and
      the presence of comorbid conditions such as cardiopulmonary disease. The
      mortality and utilization of healthcare resources associated with influenza is
      concentrated in the elderly and those with coexisting disease such as chronic
      obstructive pulmonary disease (COPD). Increasing use of vaccination and the
      development of new antiviral drugs hold out hope that the burden of disease
      associated with influenza can be reduced. However the constant emergence of new
      influenza strains and the current risk of avian influenza pandemic serve as
      warnings that influenza will remain a serious pathogen for the foreseeable
      future.

PMID- 18044067
TI  - Effects of active tobacco smoking on the prevalence of asthma-like symptoms in
      adolescents.
AB  - The prevalence of asthma in adolescents markedly varies between different
      localities as found by the International Study of Asthma and Allergies in
      Childhood (ISAAC) and this may be due to environmental factors. Although tobacco
      smoke exposure is related to an increase in the prevalence of asthma, there is
      lack of information on that respect in children from developing countries, where
      active tobacco smoking usually starts early in adolescence. This study was
      undertaken to assess the effect of tobacco smoking on the prevalence of asthma
      symptoms in a random sample of 4738 adolescents aged 13.4 +/- 1.05 years who
      responded the ISAAC video questionnaires plus questions on tobacco smoking. The
      prevalence of tobacco smoking in the last 12 months was 16.2%, with significant
      female predominance. The persistent smokers had a significantly higher prevalence
      of asthma-like symptoms ever and in the last 12 months (wheezing, wheezing with
      exercise, nocturnal wheezing, severe wheezing, and dry nocturnal cough) than ex
      smokers and nonsmokers. More than 27% of asthma symptoms in our adolescents are
      attributable to active tobacco consumption (population attributable risk). This
      study strongly suggests that potent and more effective campaigns against tobacco
      smoking should be implemented in developing countries, where active tobacco
      smoking is dramatically increasing in children.

PMID- 18044068
TI  - Variability of exhaled breath condensate leukotriene B4 and 8-isoprostane in COPD
      patients.
AB  - The reproducibility of exhaled breath condensate (EBC) mediators is not well
      documented in chronic obstructive pulmonary disease (COPD). This study assessed
      within assay (WA), within (WD) and between day (BD) reproducibility of EBC
      leukotriene B4 (LTB4) and 8-isoprostane. Three EBC samples were collected from 24
      COPD patients separated by 1 h and 1 wk, to assess WD and BD reproducibility. WA
      reproducibility was assessed by sample analysis by enzyme immunoassay in
      triplicate. WA coefficient of variation for LTB4 and 8-isoprostane (18.2% and
      29.2%, respectively) was lower than corresponding values for WD (47.7% and 65.3%,
      respectively) and BD (75.7% and 79.1%, respectively). Repeatability coefficient
      for 8-isoprostane and LTB4 assays were 18.6 pg/ml and 13.2 pg/ml, respectively.
      Group mean differences for WD and BD were small and statistically nonsignificant.
      Using the Bland Altman method, there were wide limits of agreement for WD (-51.6
      to 47.2 for 8-isoprostane and -31.8 to 31.4 for LTB4) and BD reproducibility (
      61.4 to 75.7 for 8-isoprostane and -29.3 to 38.6 for LTB4). This is the first
      study to fully report the variability of EBC 8-isoprostane and LTB4 in COPD. WA
      variability and group mean changes were small. However, we observed considerable
      WD and BD variability for these biomarkers.

PMID- 18044069
TI  - Effects of acute hypoxia on left and right ventricular contractility in chronic
      obstructive pulmonary disease.
AB  - The purpose of this investigation was to assess the effects of acute hypoxia on
      left (LV) and right ventricular (RV) contractility in clinically stable chronic
      obstructive pulmonary disease (COPD) patients. Eleven male patients (mean age
      52.4 +/- 12.6 years) who were diagnosed to have COPD were included into the
      study. All of the patients underwent left and right heart catheterization. RV
      contractility was measured according to the method of Ferlinz and LV
      contractility according to the method of Kennedy and colleagues using indirect
      digital substraction angiography. Mean pulmonary artery pressures (Mean PPA) and
      oxygen saturation of the pulmonary artery (SaO2) were measured before and at each
      stage of graded hypoxic exposure 14%, 12%, and 10% of O2. Right atrial pressures
      (PRA,syst, PRA,diast, PRA,mean), RV pressures (PRV,syst, PRV,diast, PRV,mean,
      PRV,end-diast), RV and LV end-diastolic volume index (EDVI), end-systolic volume
      index (ESVI), stroke volume index (SVI), cardiac index (CI), ejection fraction
      (EF), and heart rate (HR) were calculated before and after breathing a hypoxic
      mixture of 10% of O2 for 30 minutes. Acute hypoxia induced significant elevation
      of mean PPA, PRA,syst, PRA,diast, PRA,mean, PRV,syst, PRV,mean, PRV,end-diast, RV
      EDVI, RV ESVI, LV EDVI, LV ESVI, confidence interval, and HR (p < 0.05). Whereas
      SaO2 decreased significantly after acute hypoxia (p < 0.05). These findings
      suggest that the systolic performance of the right and left ventricles were well
      maintained during acute hypoxia in patients with COPD.

PMID- 18044071
TI  - What's in a name?

PMID- 18044070
TI  - Stress distribution in a three dimensional, geometric alveolar sac under normal
      and emphysematous conditions.
AB  - Pulmonary emphysema is usually the result of chronic exposure to cigarette smoke
      in at risk individuals. To investigate the hypothesis that lung damage in
      emphysema results from coincident weakening in the structural properties of the
      tissue and increased mechanical forces--as one explanation of the continued
      development of pulmonary emphysema after smoking cessation--we developed a three
      dimensional, geometric dodecahedron-based acinar model. Using the model numerical
      analysis of the stress distribution in normal conditions could be compared with
      those resulting in emphysematous conditions. Finite element analysis was used to
      evaluate the model at a number of lung inflation levels, using quasi-static
      loading of the alveolar pressure. When internal alveolar pressure was increased
      along with the adjustment of the material properties to represent a weakening of
      one wall in the acinus, increased stress resulted at the perimeters of the
      weakened area. In particular this increased stress was localized at the junction
      points of the internal alveolar septa. It was also found that under the proposed
      simulated emphysematous conditions, a significant disruption in the stress
      distribution within the acinus model occurred at low, rather than high, lung
      volumes. This is supportive of the physiological observation that destruction of
      the diseased tissue can occur under less stress than those existing in the normal
      state.

PMID- 18044072
TI  - Immunological outcomes of exercise in older adults.
AB  - Aging is associated with a dysregulation of the immune system known as
      immunosenescence. Immunosenescence involves cellular and molecular alterations
      that impact both innate and adaptive immunity, leading to increased incidences of
      infectious disease morbidity and mortality as well as heightened rates of other
      immune disorders such as autoimmunity, cancer, and inflammatory conditions. While
      current data suggests physical activity may be an effective and logistically easy
      strategy for counteracting immunosenescence, it is currently underutilized in
      clinical settings. Long-term, moderate physical activity interventions in
      geriatric populations appear to be associated with several benefits including
      reduction in infectious disease risk, increased rates of vaccine efficacy, and
      improvements in both physical and psychosocial aspects of daily living. Exercise
      may also represent a viable therapy in patients for whom pharmacological
      treatment is unavailable, ineffective, or inappropriate. The effects of exercise
      impact multiple aspects of immune response including T cell phenotype and
      proliferation, antibody response to vaccination, and cytokine production.
      However, an underlying mechanism by which exercise affects numerous cell types
      and responses remains to be identified. Given this evidence, an increase in the
      use of physical activity programs by the healthcare community may result in
      improved health of geriatric populations.

PMID- 18044073
TI  - Rivastigmine in the treatment of Alzheimer's disease: an update.
AB  - Alzheimer's disease is the most common form of dementia in industrialized
      countries. In the European Union, about 54% of dementia cases are believed to be
      due to Alzheimer's disease. The condition is an age-related neurodegenerative
      disorder characterized by multiple cognitive deficiencies, including loss of
      memory, judgment, and comprehension. These manifestations are accompanied by
      behavioral and mood disturbances. Although no cure has yet been discovered for
      Alzheimer's disease, symptomatic therapies are now widely available and offer
      significant relief to patients and benefits to caregivers in terms of reduced
      care burden. At the start of the 21st century, health technology assessments
      recommended three agents for the symptomatic treatment of mild to moderate
      Alzheimer disease: rivastigmine, donepezil, and galantamine. Rivastigmine
      (Exelon, Novartis Basel-Switzerland) is a slowly reversible inhibitor of
      acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), while donepezil
      (Aricept, Pfizer, New York, USA) and galantamine (Reminyl, Janssen, New Jersey,
      USA) show no functional inhibition of BuChE, and are considered AChE-selective,
      rapidly-reversible inhibitors. The efficacy of all three agents has been
      evaluated in large, double-blind, placebo-controlled clinical trials of up to 6
      months' duration. Rivastigmine treatment in mild to moderate Alzheimer's disease
      improves cognition, activities of daily living, and global function.

PMID- 18044076
TI  - Quarterly intravenous injection of ibandronate to treat osteoporosis in
      postmenopausal women.
AB  - Osteoporosis is a chronic condition that generally requires long-term therapy for
      fracture risk reduction to become apparent. Although the bisphosphonates have
      made a major contribution to how clinicians manage osteoporosis, compliance with
      therapy has generally been less in the real-world setting than seen in clinical
      trials. Less-frequently administered dosage regimens or nonoral routes may
      enhance compliance and so maximize the therapeutic benefit of bisphosphonates.
      Ibandronate is a nitrogen-containing bisphosphonate, whose high potency allows it
      to be administered orally or intravenously with extended dosing intervals. This
      paper will review the role of intravenous ibandronate in the treatment of
      postmenopausal osteoporosis.

PMID- 18044075
TI  - The differential effects of bisphosphonates, SERMS (selective estrogen receptor
      modulators), and parathyroid hormone on bone remodeling in osteoporosis.
AB  - Osteoporosis is a skeletal metabolic disease characterized by a compromised bone
      fragility, leading to an increased risk of developing spontaneous and traumatic
      fractures. Osteoporosis is considered a multifactorial disease and fractures are
      the results of several different risk factors both extra- and intraskeletal. Thus
      bone fragility can be the end point of several different causes: a) failure to
      reach an optimal peak bone mass during growth; b) excessive bone resorption
      resulting in decreased bone mass and microarchitectural deterioration; c)
      inadequate formation upon an increased resorption during the process of bone
      remodeling. The pharmacological therapeutical options, available to date, are
      directed on prevention of fractures. The aim of this paper is to describe the
      activities and the mechanisms of action, as known at present, of the most used
      therapies for osteoporosis and their clinical implications. Improvement of
      knowledge in this field will allow us to further improve therapeutical choices
      and pharmacological interventions.

PMID- 18044077
TI  - Activity and potential role of licofelone in the management of osteoarthritis.
AB  - Osteoarthritis is the most common form of arthritis. It is a progressive joint
      disease associated with aging. It may be found in the knees, hips, or other
      joints. It is estimated that costs associated with osteoarthritis exceed 2% of
      the gross national product in developed countries. Nonsteroidal anti-inflammatory
      drugs (NSAIDs) are a mainstay in the treatment of inflammatory disease and are
      among the most widely used drugs worldwide. The main limitation in using NSAIDs
      consists in their side-effects, including gastrointestinal ulcerogenic activity
      and bronchospasm. The mechanism of action of these drugs is attributed to the
      inhibition of cyclooxygenase (COX), and, consequently, the conversion of
      arachidonic acid into prostaglandins. It is hypothesized that the undesirable
      side-effects of NSAIDs are due to the inhibition of COX-1 (constitutive isoform),
      whereas the beneficial effects are related to the inhibition of COX-2 (inducible
      isoform). Arachidonic acid can also be converted to leukotrienes (LTs) by the
      action of 5-lipoxygenase (5-LOX). Licofelone, a LOX/COX competitive inhibitor,
      decreases the production ofproinflammatory leukotrienes and prostaglandins (which
      are involved in the pathophysiology of osteoarthritis and in gastrointestinal
      (GI) damage induced by NSAIDs) and has the potential to combine good analgesic
      and anti-inflammatory effects with excellent GI tolerability. Preliminary data
      with this drug seem promising, but further well-designed clinical trials of this
      agent in the elderly will be necessary before a final evaluation is possible.

PMID- 18044078
TI  - Cosmetic use of botulinum toxin type A in the elderly.
AB  - Botulinum toxin type A injections are one of the most popular cosmetic procedures
      for diminishing the appearance of facial lines caused by habitual facial muscle
      contractions. Although the manufacturer's labeling recommends botulinum toxin
      only for the treatment of glabellar lines among adults younger than 65 years of
      age, there is widespread use of the toxin for other cosmetic purposes and for
      patients who may be older than 65. Evidence-based safety and efficacy data on
      botulinum toxin use in elderly patients is limited. However, given the age
      related skin changes and multifactorial causes of wrinkles in the elderly, as
      well as the higher risk for potential side effects due to concomitant diseases
      and medications, a careful risk-benefit assessment should precede the decision to
      use botulinum toxin in the elderly patient.

PMID- 18044074
TI  - Immunosupportive therapies in aging.
AB  - The primary role of the immune system is to protect the organism against
      pathogens, but age-associated alterations to immunity increase the susceptibility
      of the elderly to infectious disease. The exact nature of these changes is still
      controversial, but the use of screening procedures, such as the SENIEUR protocol
      to exclude underlying illness, helped to better characterize the changes actually
      related to physiological aging rather than pathology. It is generally agreed that
      the most marked changes occur in the cellular immune response reflecting profound
      alterations in T cells. Much of this is due to thymic involution as well as
      changes in the proportions of T cell subpopulations resulting from antigen
      exposure, and altered T cell activation pathways. However, a body of data
      indicates that innate immune responses, including the critical bridge between
      innate and adaptive immunity, and antigen presenting capacity are not completely
      resistant to senescence processes. The consequences of all these alterations are
      an increased incidence of infections, as well as possibly cancers, autoimmune
      disorders, and chronic inflammatory diseases. The leading question is what, if
      anything, can we do to prevent these deleterious changes without dangerously
      dysregulating the precarious balance of productive immunity versus
      immunopathology? There are many potential new therapeutic means now available to
      modulate immunosenescence and many others are expected to be available shortly.
      One main problem in applying these experimental therapies is ethical: there is a
      common feeling that as ageing is not a disease; the elderly are not sick and
      therefore do not require adventurous therapies with unpredictable side-effects in
      mostly frail individuals. Animal models are not helpful in this context. In this
      chapter we will first briefly review what we think we know about human
      immunosenescence and its consequences for the health status of elderly
      individuals. We will then discuss possible interventions that might one day
      become applicable in an appropriate ethical environment.

PMID- 18044079
TI  - Long-term management of GERD in the elderly with pantoprazole.
AB  - The prevalence of gastroesophageal reflux disease (GERD) increases with age and
      elderly are more likely to develop severe disease. Older patients often complain
      of less severe or frequent heartburn than younger patients and they may present
      with atypical symptoms such as dysphagia, weight loss, or extraesophageal
      symptoms. Proton pump inhibitors (PPIs) are central in the management of GERD and
      are unchallenged with regards to their efficacy. They are considered safe and
      more effective than histamine receptor antagonists for healing esophagitis and
      for preventing its recurrence using a long term maintenance treatment. PPI have
      minimal side effects and few slight drug interactions and are considered safe for
      long term treatment. Pantoprazole is significantly effective both for acute and
      long-term treatment with excellent control of relapse and symptoms. It is well
      tolerated even for long-term therapy and its tolerability is optimal.
      Pantoprazole shows to have minimal interactions with other drugs because of a
      lower affinity for cytocrome P450 than older PPIs. Although the majority of
      elderly has concomitant illnesses and receive other drugs, this does not
      adversely effect the efficacy of pantoprazole because of its pharmacokinetics,
      which are independent of patient age. Clinical practice suggests that a low dose
      maintenance of PPIs should be used in older patients with GERD.

PMID- 18044080
TI  - A review of a bi-layered living cell treatment (Apligraf) in the treatment of
      venous leg ulcers and diabetic foot ulcers.
AB  - Apligraf (Organogenesis, Canton, MA) is a bi-layered bioengineered skin
      substitute and was the first engineered skin US Food and Drug Administration
      (FDA)-approved to promote the healing of ulcers that have failed standard wound
      care. Constructed by culturing human foreskin-derived neonatal fibroblasts in a
      bovine type I collagen matrix over which human foreskin-derived neonatal
      epidermal keratinocytes are then cultured and allowed to stratify, Apligraf
      provides both cells and matrix for the nonhealing wound. Its exact mechanism of
      action is not known, but it is known to produce cytokines and growth factors
      similar to healthy human skin. Initially approved by the FDA in 1998 for the
      treatment of venous ulcers greater than one-month duration that have not
      adequately responded to conventional therapy, Apligraf later received approval in
      2000 for treatment of diabetic foot ulcers of greater than three weeks duration.
      Herein, we review the use of Apligraf in the treatment of chronic venous leg
      ulcers and diabetic foot ulcers. Our goal is to provide a working understanding
      of appropriate patient selection and proper use of the product for any physician
      treating this segment of the aging population.

PMID- 18044081
TI  - Update on the use of dutasteride in the management of benign prostatic
      hypertrophy.
AB  - Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary symptoms,
      with a prevalence of 50% by the sixth decade of life. Hyperplasia of stromal and
      epithelial prostatic elements that surround the urethra cause lower urinary tract
      symptoms (LUTS), urinary tract infection, and acute urinary retention. Medical
      treatments of symptomatic BPH include; 1) the 5alpha-reductase inhibitors, 2) the
      alpha1-adrenergic antagonists, and 3) the combination of a 5alpha-reductase
      inhibitor and a alpha1-adrenergic antagonist. Selective alpha1-adrenergic
      antagonists relax the smooth muscle of the prostate and bladder neck without
      affecting the detrussor muscle of the bladder wall, thus decreasing the
      resistance to urine flow without compromising bladder contractility. Clinical
      trials have shown that alpha1-adrenergic antagonists decrease LUTS and increase
      urinary flow rates in men with symptomatic BPH, but do not reduce the long-term
      risk of urinary retention or need for surgical intervention. Inhibitors of 5alpha
      reductase decrease production of dihydrotestosterone within the prostate
      resulting in decreased prostate volumes, increased peak urinary flow rates,
      improvement of symptoms, and decreased risk of acute urinary retention and need
      for surgical intervention. The combination of a 5alpha-reductase inhibitor and a
      alpha1-adrenergic antagonist reduces the clinical progression of BPH over either
      class of drug alone.

PMID- 18044082
TI  - Cataract surgery and quality of life implications.
AB  - Cataract surgery in the developed world has undergone a revolution over the last
      20 years. An operation which used to require a stay in hospital and long visual
      rehabilitation is now a quick day-case procedure with immediate benefits. As with
      any surgery there is an associated morbidity, but there is now the potential to
      provide cataract surgery at an earlier stage of cataract maturation and save
      patients from a period of severe visual impairment. This article reviews the new
      techniques available to measure the impact that cataracts have not only on a
      patient's visual acuity but also their general physical health, function,
      cognition, and emotional well-being. New research is described that takes into
      account these more holistic tests and how they can be used to judge the best time
      to refer and operate on a patient with cataracts.

PMID- 18044083
TI  - Mediterranean diet and prevention of coronary heart disease in the elderly.
AB  - There are now several scientific studies that relate this traditional dietary
      pattern with the incidence of coronary heart disease, various types of cancer,
      and other diseases. The past years have several observational and clinical
      studies suggested the mechanisms by which this traditional diet may affect
      coronary risk. This review underlines the importance of the Mediterranean dietary
      patterns in the prevention of coronary heart disease.

PMID- 18044084
TI  - Can health promotion programs save Medicare money?
AB  - The impact of an aging population on escalating US healthcare costs is influenced
      largely by the prevalence of chronic disease in this population. Consequently,
      preventing or postponing disease onset among the elderly has become a crucial
      public health issue. Fortunately, much of the total burden of disease is
      attributable to conditions that are preventable. In this paper, we address
      whether well-designed health promotion programs can prevent illness, reduce
      disability, and improve the quality of life. Furthermore, we assess evidence that
      these programs have the potential to reduce healthcare utilization and related
      expenditures for the Medicare program. We hypothesize that seniors who reduce
      their modifiable health risks can forestall disability, reduce healthcare
      utilization, and save Medicare money. We end with a discussion of a new Senior
      Risk Reduction Demonstration, which will be initiated by the Centers for Medicare
      and Medicaid Services in 2007, to test whether risk reduction programs developed
      in the private sector can achieve health improvements among seniors and a
      positive return on investment for the Medicare program.

PMID- 18044085
TI  - Walker use, but not falls, is associated with lower physical functioning and
      health of residents in an assisted-living environment.
AB  - The relationship between perceived health and walker use has seldom been
      addressed. Concerns over falls and falls risk are precursors to walker use. We
      compared the SF-36 scores of 26 women and 14 men, mean age 86.8 +/- 6.0 years
      based on walker use and faller status. An analysis of covariance (ANCOVA) with
      age as the covariate, compared groups for the SF-36 constructs and totals score.
      Significant differences were noted between walker users and nonusers in physical
      functioning, role limitations due to physical problems, general health, and the
      total SF-36 score. Pairwise comparisons favored nonusers, while no differences
      were seen due to faller status. Walker use is associated with lower self
      perceptions of physical functioning, role limitations due to physical problems,
      and general health in assisted-living residents. Faller status is not associated
      with self-perceived health status. Although walker use aids mobility and lowers
      the probability of falls, further research is needed to determine if the
      prescription of assistive devices has a more negative impact on self-perceived
      health than does falling. This possibility could be explained, in part, by the
      greater activity levels of those individuals who do not depend on walkers.

PMID- 18044086
TI  - Factors contributing to fecal incontinence in older people and outcome of routine
      management in home, hospital and nursing home settings.
AB  - OBJECTIVE: Fecal loading, cognitive impairment, loose stools, functional
      disability, comorbidity and anorectal incontinence are recognized as factors
      contributing to loss of fecal continence in older adults. The objective of this
      project was to assess the relative distribution of these factors in a variety of
      settings along with the outcome of usual management. METHODS: One hundred and
      twenty adults aged 65 years and over with fecal incontinence recruited by
      convenience sampling from four different settings were studied. They were either
      living at home or in a nursing home or receiving care on an acute or
      rehabilitation elderly care ward. A structured questionnaire was used to elicit
      which factors associated with fecal incontinence were present from subjects who
      had given written informed consent or for whom assent for inclusion in the study
      had been obtained. RESULTS: Fecal loading (Homes 6 [20%]; Acute care wards 17
      [57%]; Rehabilitation wards 19 [63%]; Nursing homes 21 [70%]) and functional
      disability (Homes 5 [17%]; Acute care wards 25 [83%]; Rehabilitation wards 25
      [83%]; Nursing homes 20 [67%]) were significantly more prevalent in the hospital
      and nursing home settings than in those living at home (P < 0.01). Loose stools
      were more prevalent in the hospital setting than in the other settings (Homes 11
      [37%]; Acute care wards 20 [67%]; Rehabilitation wards 17 [57%]; Nursing homes 6
      [20%]) (P < 0.01). Cognitive impairment was significantly more common in the
      nursing home than in the other settings (Nursing homes 26 [87%], Homes 5 [17%],
      Acute care wards 13 [43%], Rehabilitation wards 14 [47%]) (P < 0.01). Loose
      stools were the most prevalent factor present at baseline in 13 of the 19 (68%)
      subjects whose fecal incontinence had resolved at 3 months. CONCLUSION: The
      distribution of the factors contributing to fecal incontinence in older people
      living at home differs from those cared for in nursing home and hospital wards
      settings. These differences need to be borne in mind when assessing people in
      different settings. Management appears to result in a cure for those who are not
      significantly disabled with loose stools as a cause for their fecal incontinence,
      but this would need to be confirmed by further research.

PMID- 18044087
TI  - Effect of vitamin C supplementation on stroke recovery: a case-control study.
AB  - BACKGROUND AND PURPOSE: Epidemiological studies have associated increased dietary
      intake of antioxidants (vitamin C, E, and beta-carotene) in preventing and
      decreasing the extent of ischemic brain injury. The effect of vitamin C
      supplementation on functional recovery after stroke has not been studied. METHOD:
      In this retrospective, case-control study of 23 patients with ischemic stroke
      taking vitamin C were identified and matched for age, sex, onset to admission,
      and admission total functional independence measure (TFIM) with 23 patients with
      ischemic stroke not taking Vitamin C supplementation. Vitamin C 1000 mg daily was
      prescribed on admission to our unit mainly to patients who were undernourished
      (defined as significant weight loss and/or 90% or less ideal body weight for age
      and sex) and those with pressure sores. The outcome measures were: change in the
      TFIM, FIM-Cognition (FIM-Cog), and FIM-Motor sub-scores, discharge disposition,
      and length of stay (LOS). RESULTS: The change in TFIM (20 +/- 13 standard
      deviation [SD] vs. 26 +/- 6, p = 0.20), FIM-Cog (3 +/- 3 SD vs. 4 +/- 5, p =
      0.41), FIM-Motor (15 +/- 11 SD vs. 20 +/- 13, p = 0.21) sub-scores were less in
      the vitamin C treated group, but these differences did not reach statistical
      significance. Similarly, no significant differences were found in LOS (21 +/- 9
      SD vs. 23 +/- 9, p = 0.59), and discharge disposition (home/institution) (9/10
      vs. 13/9, p = 0.60) between the vitamin C and the control groups. CONCLUSION:
      This study suggests vitamin C supplementation did not enhance functional recovery
      in undernourished ischemic stroke patients.

PMID- 18044088
TI  - Is it necessary to cure prostate cancer when it is possible? (Understanding the
      role of prostate inflammation resolution to prostate cancer evolution).
AB  - OBJECTIVE: Definitive therapy with radical prostatectomy, cryotherapy, or
      radiation therapy generally follows the initial diagnosis of prostate cancer,
      particularly when men have at least 10 additional years of life expectancy. There
      is growing concern regarding the optimal conservative treatment for patients who
      decline or do not otherwise qualify for such definitive curative treatment. For
      those patients who choose a watchful waiting approach, it would be beneficial to
      know what specific dietary and nutritional methods could potentially slow the
      progression of their disease. In this prospective study, it was our goal to
      analyze the efficacy and safety of treating prostate cancer conservatively using
      the principles of a Mediterranean diet in association with a specific prostate
      nutritional supplement. METHOD: Twenty-three men aged 43-74 (median age: 64) with
      biopsy proven, organ-confined prostate cancer who had already declined immediate
      hormonal therapy and attempts at a curative cancer treatment agreed to
      participate in a Chronic Disease Management (CDM) protocol highlighted by diet
      with a specific prostate nutritional supplement. The diet recommended was a
      modified Mediterranean diet while a patented nutritional prostatitis formula
      (Peenuts) was the supplement common to all patients. Prostate specific antigen
      (PSA), a recognized marker of prostate disease and prostate cancer activity, was
      the primary indicator to validate exacerbation or suppression of disease. All men
      were followed with serial PSA testing, a digital rectal exam, an International
      Prostate Symptom Score index (IPSS-Index) and an expressed prostatic secretion
      (EPS) examination. The primary Gleason sum/score represented in this study was 6
      (n = 11), while Gleason sum patterns 5, 5/6, 6/7, and 7 were also evaluated.
      Referencing the Partin Tables, organ confinement was predicted to be 66%.
      RESULTS: Eighty-seven percent of men (n = 20) noted a 58% reduction (range of
      improvement: 13%-90%) in PSA over an average of 38.5 months (range: 13-84
      months). The remaining 13% of men included three men who experienced a mild
      elevation in PSA of 0.3 ng/ml, 0.7 ng/ml, and 0.9 ng/ml over 14 months, 42
      months, and 34 months, respectively. Fifteen men had completed an initial and
      secondary IPSS-Index while 14 men had undergone an initial and secondary EPS. The
      mean percentage reduction in IPSS-Index was 61% (range: 20%-100% with a median of
      55%), while men evaluated with EPS examinations noted a mean percentage reduction
      in white blood cells of 77.5% (range: 33%-99% with a median of 82%). These
      results were evaluated using the t-test, Wilcoxon Analysis and the Null
      Hypothesis and found to be statistically significant. CONCLUSION: Clearly there
      is a need to develop effective alternative conservative therapies for the
      increasing numbers of prostate cancer patients who will not tolerate definitive
      curative measures or simply choose a conservative approach. Although this
      prospective study had no control arm, was of limited duration and included only
      23 participants, it did appear to show significant benefit to the majority of
      prostate cancer patients treated with selective nutritional and dietary therapy
      alone. Such treatments may provide a safe and effective long-term treatment
      alternative for some patients. Further study is encouraged.

PMID- 18044089
TI  - Full length parathyroid hormone (1-84) in the treatment of osteoporosis in
      postmenopausal women.
AB  - OBJECTIVE: To review the pharmacological properties and the available clinical
      data of full length parathyroid hormone (PTH) in post-menopausal osteoporosis.
      SOURCES: A MEDLINE search was completed, together with a review of information
      obtained from the manufacturer and from the medicine regulatory agencies. STUDY
      AND DATA SELECTION: Studies were selected according to relevance and
      availability. Relevant information (design, objectives, patients'
      characteristics, outcomes, adverse events, dosing, etc) was analyzed. RESULTS:
      Different studies have shown that, when administered intermittently as a
      subcutaneous injection in the abdomen, PTH increases bone mineral density (BMD)
      and prevents vertebral fractures. On completion of PTH therapy (up to 24 months),
      there is evidence that sequential treatment with alendronate is associated with a
      therapeutic benefit in terms of increase in BMD. Further trials are necessary to
      determine long-term safety and the role of PTH in combination with other
      treatments for osteoporosis and the effect of repeated cycles of PTH followed by
      an anti-catabolic agent. There are currently no completed comparative trials with
      other osteoporosis treatments. CONCLUSIONS: Full length PTH, given intermittently
      as an abdominal subcutaneous injection, appears to be a safe and efficacious
      treatment option for high risk osteoporosis. More data are needed to determine
      its specific role in osteoporosis treatment.

PMID- 18044090
TI  - Diagnosing COPD.

PMID- 18044091
TI  - The role of combination therapy with corticosteroids and long-acting beta2
      agonists in the prevention of exacerbations in COPD.
AB  - Acute exacerbations of COPD can complicate the course of the disease in patients
      with severe airway obstruction. Reduction of exacerbations is an important
      clinical outcome in evaluating new therapies in COPD. Combination therapies with
      long-acting beta-agonists and inhaled corticosteroids have now been approved for
      use. Three 1-year randomized clinical trials, which studied the effect of
      combining a long-acting beta2-agonist with an inhaled corticosteroid in COPD,
      documented that exacerbation frequency was lower with therapy than placebo.
      Combination therapy had a similar effect to its monocomponents in the trial
      evaluating salmeterol/fluticasone combination. However, when patients with more
      severe COPD were studied using a combination of budesonide and formoterol, a
      clear improvement was seen in the overall exacerbation rates compared with the
      use of a long-acting beta2-agonist alone.

PMID- 18044092
TI  - Is there any treatment other than drugs to alleviate dyspnea in COPD patients?
AB  - Patients with chronic obstructive pulmonary disease (COPD) are often limited in
      their activities by breathlessness. In these patients, exercise training may
      result in significant improvements in dyspnea, exercise tolerance, and health
      related quality of life (HRQoL). Further possibilities are to reduce ventilatory
      demand by decreasing the central respiratory drive or to lessen the perceived
      breathing effort by increasing respiratory muscle strength through specific
      respiratory muscle training. Upper limb training may also improve exercise
      capacity and symptoms in these patients through the modulation of dynamic
      hyperinflation. Ventilatory assistance during exercise reduces dyspnea and work
      of breathing and enhances exercise tolerance, although further studies should be
      required to define their applicability in the routine pulmonary rehabilitation
      programs. Lung volume resection surgery and lung transplantation in selected
      patients may control symptoms and improve HRQoL.

PMID- 18044093
TI  - Respiratory disorders during sleep in chronic obstructive pulmonary disease.
AB  - Patients with COPD may show slow, progressive deteriorations in arterial blood
      gases during the night, particularly during rapid eye movement (REM) sleep. This
      is mainly due to hypoventilation, while a deterioration of ventilation/perfusion
      mismatch plays a minor role. The severity of gas exchanges alterations is
      proportional to the degree of impairment of diurnal pulmonary function tests,
      particularly of partial pressure of oxygen (PaO2) and of carbon dioxide (PaCO2)
      in arterial blood, but correlations between diurnal and nocturnal blood gas
      levels are rather loose. Subjects with diurnal PaO2 of 60-70 mmHg are
      distinguished in "desaturators" and "nondesaturators" according to nocturnal
      oxyhemoglobin saturation behavior. The role of nocturnal hypoxemia as a
      determinant of alterations in sleep structure observed in COPD is dubious.
      Effects of the "desaturator" condition on pulmonary hemodynamics, evolution of
      diurnal blood gases, and life expectancy are also controversial. Conversely, it
      is generally accepted that occurrence of sleep apneas in COPD is associated with
      a worse evolution of the disease. Nocturnal polysomnographic monitoring in COPD
      is usually performed when coexistence of sleep apnea ("overlap syndrome") is
      suspected, while in most other cases nocturnal oximetry may be enough. Nocturnal
      oxygen attenuates sleep desaturations among stable patients, without increases in
      PaCO2 of clinical concern. Nocturnal treatment with positive pressure ventilators
      may give benefit to some stable hypercapnic subjects and patients with the
      overlap syndrome.

PMID- 18044094
TI  - Evaluation of PDE4 inhibition for COPD.
AB  - Targeting type 4 phosphodiesterase (PDE4) for treatment of COPD has multilevel
      benefits to patients by reducing inflammation, relieving bronchoconstriction, and
      improving pulmonary circulation. The isoenzyme-specific narrow spectrum PDE4
      inhibitors such as cilomilast and roflumilast may have limited clinical efficacy
      in managing severe and very severe COPD. Development of dual therapy by combining
      PDE4 inhibition with Ca2+ channel antagonism may introduce an effective novel
      armory for physicians to manage patients with severe COPD.

PMID- 18044096
TI  - Immediate and early discharge for patients with exacerbations of chronic
      obstructive pulmonary disease: is there a role in "real life"?
AB  - An exacerbation of chronic obstructive pulmonary disease (COPD) is the most
      common respiratory condition necessitating admission to hospital. Many of these
      are relatively mild in nature and as a consequence, there is increasing interest
      in immediate and early discharge of patients with nonsevere exacerbations.
      Following initial assessment, "hospital at home" or "assisted discharge" schemes
      enable suitable patients with COPD to be discharged into the community earlier
      than normally anticipated. The putative implication is that substantial financial
      savings can be made in addition to increasing the availability of in-patient
      beds, without compromising patient care or satisfaction. We highlight the current
      literature which has evaluated the role of hospital at home and assisted
      discharge schemes and discuss our own "real life" service operating in a large
      teaching hospital in Scotland.

PMID- 18044095
TI  - Hyperinflation and its management in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by poorly
      reversible airflow limitation. The pathological hallmarks of COPD are
      inflammation of the peripheral airways and destruction of lung parenchyma or
      emphysema. The functional consequences of these abnormalities are expiratory
      airflow limitation and dynamic hyperinflation, which then increase the elastic
      load of the respiratory system and decrease the performance of the respiratory
      muscles. These pathophysiologic features contribute significantly to the
      development of dyspnea, exercise intolerance and ventilatory failure. Several
      treatments may palliate flow limitation, including interventions that modify the
      respiratory pattern (deeper, slower) such as pursed lip breathing, exercise
      training, oxygen, and some drugs. Other therapies are aimed at its amelioration,
      such as bronchodilators, lung volume reduction surgery or breathing mixtures of
      helium and oxygen. Finally some interventions, such as inspiratory pressure
      support, alleviate the threshold load associated to flow limitation. The degree
      of flow limitation can be assessed by certain spirometry indexes, such as vital
      capacity and inspiratory capacity, or by other more complexes indexes such as
      residual volume/total lung capacity or functional residual capacity/total lung
      capacity. Two of the best methods to measure flow limitation are to superimpose a
      flow-volume loop of a tidal breath within a maximum flow-volume curve, or to use
      negative expiratory pressure technique. Likely this method is more accurate and
      can be used during spontaneous breathing. A definitive definition of dynamic
      hyperinflation is lacking in the literature, but serial measurements of
      inspiratory capacity during exercise will document the trend of end-expiratory
      lung volume and allow establishing relationships with other measurements such as
      dyspnea, respiratory pattern, exercise tolerance, and gas exchange.

PMID- 18044097
TI  - Pharmacological treatment of chronic obstructive pulmonary disease.
AB  - None of the drugs currently available for chronic obstructive pulmonary disease
      (COPD) are able to reduce the progressive decline in lung function which is the
      hallmark of this disease. Smoking cessation is the only intervention that has
      proved effective. The current pharmacological treatment of COPD is symptomatic
      and is mainly based on bronchodilators, such as selective beta2-adrenergic
      agonists (short- and long-acting), anticholinergics, theophylline, or a
      combination of these drugs. Glucocorticoids are not generally recommended for
      patients with stable mild to moderate COPD due to their lack of efficacy, side
      effects, and high costs. However, glucocorticoids are recommended for severe COPD
      and frequent exacerbations of COPD. New pharmacological strategies for COPD need
      to be developed because the current treatment is inadequate.

PMID- 18044099
TI  - Diagnosis of airway obstruction in primary care in the UK: the CADRE (COPD and
      Asthma Diagnostic/management REassessment) programme 1997-2001.
AB  - OBJECTIVE: Asthma and COPD require different management strategies, but
      differentiation in primary care is difficult. This primary care support
      initiative observed the impact of spirometry and clinical assessment on the
      diagnosis of airway disease. MATERIALS AND METHODS: Of 61,191 patients aged > or
      =40 years being treated for respiratory conditions within 1003 UK primary care
      practices, 43,203 underwent a diagnostic review including standardized
      spirometric assessment. The proportion of patients in whom the diagnosis was
      changed by the additional information was determined. The relationship of various
      patient characteristics was compared with the baseline and review diagnoses and
      with any change in diagnosis. RESULTS: Asthma was initially diagnosed in 43% of
      patients, COPD in 35%, mixed disease in 9%, and other respiratory condition in
      13%. Patients initially diagnosed with asthma, mixed disease, or another
      condition were more likely to have their diagnosis changed at review (54%, 46%,
      and 63%, respectively) than those initially diagnosed with COPD (14%). A change
      from asthma to COPD was associated with male gender, smoking, older age, and
      reduced lung function, the opposite being associated with a change from COPD to
      asthma. CONCLUSION: In this study, a clinical review supplemented by additional
      information including spirometry highlights apparent mislabeling of significant
      numbers of patients with chronic obstructive disease in general practice with
      significant implications for individual treatment and healthcare provision. This
      study shows that the addition of more clinical information can have a major
      effect on diagnostic tendency in patients with airway disease. An initial
      diagnosis of COPD seems less likely to change following review than an asthma
      diagnosis. While it is likely that greater information leads to a more accurate
      diagnosis, the differential effect of new information on diagnostic labeling
      highlights the insecurity of the diagnostic process in primary care in the UK.

PMID- 18044098
TI  - Role of N-acetylcysteine in the management of COPD.
AB  - The importance of the underlying local and systemic oxidative stress and
      inflammation in chronic obstructive pulmonary disease (COPD) has long been
      established. In view of the lack of therapy that might inhibit the progress of
      the disease, there is an urgent need for a successful therapeutic approach that,
      through affecting the pathological processes, will influence the subsequent
      issues in COPD management such as lung function, airway clearance, dyspnoea,
      exacerbation, and quality of life. N-acetylcysteine (NAC) is a mucolytic and
      antioxidant drug that may also influence several inflammatory pathways. It
      provides the sulfhydryl groups and acts both as a precursor of reduced
      glutathione and as a direct reactive oxygen species (ROS) scavenger, hence
      regulating the redox status in the cells. The changed redox status may, in turn,
      influence the inflammation-controlling pathways. Moreover, as a mucolytic drug,
      it may, by means of decreasing viscosity of the sputum, clean the bronchi leading
      to a decrease in dyspnoea and improved lung function. Nevertheless, as successful
      as it is in the in vitro studies and in vivo studies with high dosage, its
      actions at the dosages used in COPD management are debatable. It seems to
      influence exacerbation rate and limit the number of hospitalization days,
      however, with little or no influence on the lung function parameters. Despite
      these considerations and in view of the present lack of effective therapies to
      inhibit disease progression in COPD, NAC and its derivatives with their multiple
      molecular modes of action remain promising medication once doses and route of
      administration are optimized.

PMID- 18044100
TI  - Creatine supplementation and physical training in patients with COPD: a double
      blind, placebo-controlled study.
AB  - STUDY OBJECTIVES: Patients with chronic obstructive pulmonary disease (COPD) have
      low exercise capacity and low content of high energetic phosphates in their
      skeletal muscles. The aim of the present study was to investigate whether
      creatine supplementation together with exercise training may increase physical
      performance compared with exercise training in patients with COPD. DESIGN: In a
      randomized, double-blind, placebo-controlled study, 23 patients with COPD (forced
      expiratory volume in one second [FEV1] < 70% of predicted) were randomized to
      oral creatine (n = 13) or placebo (n = 10) supplementation during an 8-week
      rehabilitation programme including exercise training. Physical performance was
      assessed by Endurance Shuttle Walking Test (ESWT), dyspnea and leg fatigue with
      Borg CR- 10, quality of life with St George's Respiratory Questionnaire (SGRQ).
      In addition, lung function test, artery blood gases, grip strength test, muscle
      strength and fatigue in knee extensors were measured. RESULTS: COPD patients
      receiving creatine supplementation increased their average walking time by 61%
      (ESWT) (p < 0.05) after the training period compared with 48% (p = 0.07) in the
      placebo group. Rated dyspnea directly after the ESWT decreased significantly from
      7 to 5 (p < 0.05) in the creatine group. However, the difference between the
      groups was not statistically significant neither in walking time nor in rated
      dyspnea. Creatine supplementation did not increase the health related quality of
      life, lung function, artery blood gases, grip strength and knee extensor
      strength/fatigue. CONCLUSIONS: Oral creatine supplementation in combination with
      exercise training showed no significant improvement in physical performance,
      measured as ESWT, in patients with COPD compared with exercise training alone.

PMID- 18044101
TI  - Use of accelerometers to characterize physical activity patterns with COPD
      exacerbations.
AB  - PURPOSE: To determine the feasibility of using an accelerometer to characterize
      physical activity patterns (PA) surrounding chronic obstructive pulmonary disease
      (COPD) exacerbations (AECOPD) in patients with COPD for 16 weeks. METHODS:
      Patients with COPD (n = 8) wore the RT3, a triaxial accelerometer (Stayhealthy,
      Monrovia, CA) during waking hours and kept daily symptom diaries. The mean vector
      magnitude unit (VMU) per minute was calculated by dividing the total VMU for the
      day by the number of minutes the device was worn. Descriptive statistics were
      used and plots were made showing PA for each subject with AECOPD markers based on
      symptom diaries and health resource utilization. RESULTS: Sample characteristics
      were: age 71 +/- 4; 5 Females; forced expiratory volume in one second (FEV1)%
      predicted: 40% +/- 16%; FEV1/forced vital capacity: 45 +/- 7; and Medical
      Research Council dyspnea scale: 2.3 +/- 0.9. Overall adherence to the monitoring
      protocol was 97.6% (Range 92%-100%) while adherence to wearing the device for at
      least 10 hours per day was 91.5% (Range 75%-99%). Mean vector magnitude units per
      minute was 117.8 +/- 47 (Range 61.4-184.1). Seven exacerbations were captured
      over a total of 896 person-days of monitoring. There were substantial intra
      individual fluctuations in daily PA during both the stable state and with
      outpatient treated exacerbations. CONCLUSIONS: Patients with COPD were able to
      adhere to a 16-week activity monitoring protocol and reported a willingness to
      wear such a device for an extended period of time if the data yield important and
      useful information for themselves and their health provider. Future work will
      need to focus first, on validating other promising devices that produce higher
      quality PA data and second, replicate this monitoring protocol with a larger
      sample of COPD patients over a longer period.

PMID- 18044103
TI  - Comparison of oxygenation in peripheral muscle during submaximal aerobic
      exercise, in persons with COPD and healthy, matched-control persons.
AB  - OBJECTIVE: The purpose of this study was to compare peripheral muscle oxygenation
      in persons with chronic obstructive pulmonary disease (COPD) to healthy control
      persons, during submaximal exercise. METHODS: Eight persons with COPD (forced
      expiratory volume in one second [FEV1] = 1.00 +/- 0.27 L) and eight healthy
      control persons (FEV, = 1.88 +/- 0.55L) performed a submaximal graded exercise
      test (GXT), and completed 4 min of constant load exercise (CON) at 50% of peak
      GXT. Measurements included oxygen uptake, heart rate, arterial oxygen saturation
      and peripheral muscle oxygenation (%StO2) at rest, during exercise, and recovery.
      RESULTS: Significantly greater workloads were attained for controls compared with
      COPD for peak GXT and CON. No significant differences in %StO2 were observed
      between groups at: rest (GXT: 29.5 +/- 22.8 vs 30.4 +/- 17.3%; CON: 33.3 +/- 15.4
      vs 35.1 +/- 17.2%); peak GXT (29.4 +/- 19.4 vs 26.5 +/- 15.9%); 4 min of CON
      (25.9 +/- 13.5 vs 34.5 +/- 21.8%); and recovery (GXT: 46.6 +/- 29.1 vs 44.3 +/-
      21.7%; CON: 40.9 +/- 21.5 vs 44.5 +/- 23.2%). CONCLUSION: These results suggest
      that peripheral skeletal muscle oxygenation is not compromised in COPD during
      submaximal exercise, and limitations in exercise capacity are most likely a
      result of muscle disuse and poor lung function.

PMID- 18044102
TI  - Randomized placebo controlled assessment of airway inflammation due to racemic
      albuterol and levalbuterol via exhaled nitric oxide testing.
AB  - STUDY OBJECTIVES: The S-stereoisomer found in racemic albuterol may have
      associated proinflammatory properties. We tested the hypothesis that airway
      inflammation as assessed by exhaled nitric oxide is no different in patients with
      COPD when using racemic albuterol relative to levalbuterol or placebo.
      MEASUREMENTS: Twelve mild to moderate COPD patients were assigned to five days
      each of nebulized racemic albuterol, levalbuterol, and saline placebo. Before and
      after each course of treatment, airway inflammation was assessed via exhaled
      nitric oxide breath testing. Secondary functional outcomes that were measured
      included spirometry, a functional assessment utilizing a six-minute walk, and
      symptoms score using the University of California, San Diego Shortness of Breath
      Questionnaire. RESULTS: There was no statistically significant difference in pre
      and post FeNO levels within and between treatment groups (p = 0.121). There were
      also no significant differences within or between treatment groups for the
      secondary outcome measurements of FEV1 (p = 0.913), functional assessment
      utilizing a six-minute walk (p = 0.838) and the symptom scores using Shortness of
      Breath Questionnaire (p = 0.500). CONCLUSION: We found no difference in mild to
      moderate COPD patients treated with racemic albuterol, levalbuterol or placebo
      for measurement of exhaled nitric oxide or the secondary outcomes that were
      measured.

PMID- 18044104
TI  - Effect of bronchodilatation on single breath pulmonary uptake of carbon monoxide
      in chronic obstructive pulmonary disease.
AB  - We studied 21 COPD patients in stable clinical conditions to evaluate whether
      changes in lung function induced by cumulative doses of salbutamol alter
      diffusing capacity for carbon monoxide (DL(CO)), and whether this relates to the
      extent of emphysema as assessed by high resolution computed tomography (HRCT)
      quantitative analysis. Spirometry and DL(CO) were measured before and after
      cumulative doses of inhaled salbutamol (from 200 microg to 1000 microg).
      Salbutamol caused significant increments of forced vital capacity (FVC), forced
      expiratory volume in one second (FEV1), and flows at 30% of control FVC taken
      from both partial and maximal forced expiratory maneuvers. Functional residual
      capacity and residual volume were reduced, while total lung capacity did not
      change significantly. DL(CO) increased progressively with the incremental doses
      of salbutamol, but this became significant only at the highest dose (1000 microg)
      and was independent of the extent of emphysema, as assessed by radiological
      parameters. No significant changes were observed in CO transfer factor (DLCO/VA)
      and alveolar volume (VA). The results suggest that changes in lung function
      induced by cumulative doses of inhaled salbutamol are associated with a slight
      but significant increase in DL(CO) irrespective of the presence and extent of
      emphysema.

PMID- 18044105
TI  - Risk factors for symptom onset in PI*Z alpha-1 antitrypsin deficiency.
AB  - BACKGROUND: In an early study of highly symptomatic patients with PI*Z alpha-1
      antitrypsin deficiency (AAT), tobacco smoking was identified as a risk factor by
      comparing the age of symptom onset in smokers and nonsmokers. Age of symptom
      onset has not been well studied in relationship to other environmental exposures.
      METHODS: Environmental exposures were assessed in 313 PI*Z adults through
      retrospective self-administered questionnaire. Age of onset of symptoms with and
      without these exposures were analyzed through survival analysis. RESULTS:
      Personal smoking was the most important risk factor, associated with earlier
      onset of cough and wheeze, and showed a dose-dependent relationship with the
      onset of dyspnea. Childhood environmental tobacco smoke (ETS) exposure was
      independently associated with younger age of onset of cough. Earlier onset of
      wheeze was also associated with childhood respiratory infections and family
      history of emphysema. The report of childhood respiratory infections was
      associated with childhood ETS exposure, but no statistically significant
      interactions were noted. CONCLUSIONS: We conclude that both personal and
      secondhand exposure to tobacco smoke in childhood are likely to accelerate the
      onset of symptoms in AAT deficient patients. Respiratory infections in childhood
      may also contribute to this risk.

PMID- 18044106
TI  - Transdermal oxybutynin in the treatment of overactive bladder.
AB  - Overactive bladder is a dreadful syndrome that affects a considerable number of
      patients. Antimuscarinics are the mainstay of pharmacotherapy for this condition.
      Transdermal (TD) oxybutynin (OXY) bypasses the first-pass metabolism and reduces
      the formation of N-desethyloxybutynin, a compound believed to be associated with
      anticholinergic side effects. The 3.9 mg matrix TD system is applied twice weekly
      and transports OXY directly into the systemic circulation. The patch can be
      applied to abdomen, buttock, and hip, and provides continuous OXY delivery that
      minimizes peak and trough fluctuations in plasma levels. In clinical trials, TD
      and oral OXY produced a significant reduction in incontinence episodes, with no
      difference between oral and TD treatments. In addition, TDOXY was similar to
      tolterodine, and it produced a significant improvement in the number of urinary
      incontinence episodes, complete continence, and urodynamic and quality of life
      parameters compared with placebo. The incidence of anticholinergic adverse events
      with TDOXY was similar to placebo. Most common adverse events were mild-moderate
      skin reactions. Treatment satisfaction survey suggested patients' preference to
      use the TD system in the future. Counseling on healthy skin care and appropriate
      product use can enhance patients' knowledge about TDOXY for overactive bladder
      treatment.

PMID- 18044107
TI  - Insulin use in elderly diabetic patients.
AB  - The prevalence of type 2 diabetes is increasing among older adults as is their
      diabetes-related mortality rate. Studies suggest that tighter glucose control
      reduces complications in elderly patients. However, too low a glycosylated
      hemoglobin (HbA1c) value is associated with increased hypoglycemia. Moreover, the
      appropriateness of most clinical trial data and standards of care related to
      diabetes management in elderly patients is questionable given their
      heterogeneity. Having guidelines to safely achieve glycemic control in elderly
      patients is crucial. One of the biggest challenges in achieving tighter control
      is predicting when peak insulin action will occur. The clinician's options have
      increased with new insulin analogs that physiologically match the insulin peaks
      of the normal glycemic state, enabling patients to achieve the tighter diabetes
      control in a potentially safer way. We discuss the function of insulin in
      managing diabetes and how the new insulin analogs modify that state. We offer
      some practical considerations for individualizing treatment for elderly patients
      with diabetes, including how to incorporate these agents into current regimens
      using several methods to help match carbohydrate intake with insulin
      requirements. Summarizing guidelines that focus on elderly patients hopefully
      will help reduce crises and complications in this growing segment of the
      population.

PMID- 18044108
TI  - Aging and cosmetic enhancement.
AB  - Obsession with a youthful appearance has become commonplace in modern society and
      has resulted in an upswing in cosmetic procedures trying to reverse the aging
      process. We selectively review the literature on aging and cosmetic surgery, with
      particular regard for the aging face. We pay attention to psychosocial aspects of
      response to such cosmetic procedures, both in terms of outcome and with respect
      to risk factors for a poor outcome.

PMID- 18044109
TI  - Pharmacologic interventions in aging hair.
AB  - The appearance of hair plays an important role in people's overall physical
      appearance and self-perception. With today's increasing life-expectations, the
      desire to look youthful plays a bigger role than ever. The hair care industry has
      become aware of this and is delivering active products directed towards meeting
      this consumer demand. The discovery of pharmacological targets and the
      development of safe and effective drugs also indicate strategies of the drug
      industry for maintenance of healthy and beautiful hair. Hair aging comprises
      weathering of the hair shaft, decrease of melanocyte function, and decrease in
      hair production. The scalp is subject to intrinsic and extrinsic aging. Intrinsic
      factors are related to individual genetic and epigenetic mechanisms with
      interindividual variation: prototypes are familial premature graying, and
      androgenetic alopecia. Currently available pharmacologic treatment modalities
      with proven efficacy for treatment of androgenetic alopecia are topical minoxidil
      and oral finasteride. Extrinsic factors include ultraviolet radiation and air
      pollution. Experimental evidence supports the hypothesis that oxidative stress
      also plays a role in hair aging. Topical anti-aging compounds include
      photoprotectors and antioxidants. In the absence of another way to reverse hair
      graying, hair colorants remain the mainstay of recovering lost hair color.
      Topical liposome targeting for melanins, genes, and proteins selectively to hair
      follicles are currently under investigation.

PMID- 18044110
TI  - Treatment of Alzheimer's disease across the spectrum of severity.
AB  - Alzheimer's disease (AD) is the most common cause of dementia affecting nearly 18
      million people around the world and 4.5 million in the US. It is a progressive
      neurodegenerative condition that is estimated to dramatically increase in
      prevalence as the elderly population continues to grow. As the cognitive and
      neuropsychiatric signs and symptoms of AD progresses in severity over time,
      affected individuals become increasingly dependent on others for assistance in
      performing all activities of daily living. The burden of caring for someone
      affected by the disorder is great and has substantial impact on a family's
      emotional, social and financial well-being. In the US, the currently approved
      medications for the treatment of mild to moderate stages of AD are the
      cholinesterase inhibitors (ChEIs). Cholinesterase inhibitors have shown modest
      efficacy in terms of symptomatic improvement and stabilization for periods
      generally ranging from 6 to 12 months. There are additional data that have
      emerged, which suggest longer-term benefits. For the moderate to severe stages of
      AD, memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist is in
      widespread use and has shown modest benefit as monotherapy and in combination
      with ChEIs. The cost effectiveness of the currently available therapeutic agents
      for AD has undergone great scrutiny and remains controversial, especially outside
      the US. Neuropsychiatric symptoms such as agitation and psychosis are common in
      AD. Unfortunately, in the US there are no Food and Drug Administration (FDA)
      approved agents for the treatment of these symptoms, although atypical
      antipsychotics have shown some efficacy and have been widely used. However, the
      use of these agents has recently warranted special caution due to reports of
      associated adverse effects such as weight gain, hyperlipidemia, glucose
      intolerance, cerebrovascular events, and an increased risk for death. Alternative
      agents used to treat neuropsychiatric symptoms include serotonergic
      antidepressants, benzodiazepines, and anticonvulsant medications.

PMID- 18044111
TI  - Economic considerations in the management of Alzheimer's disease.
AB  - Alzheimer's disease is a devastating chronic disease that significantly increases
      healthcare costs and affects the quality of life (QoL) of the afflicted patients
      and their caregivers. Population aging and other demographic changes may further
      increase the already staggering costs of this devastating disease. While few
      pharmacoeconomic studies have used a prospective health economics design to
      assess resource utilization, most studies showed beneficial treatment effects and
      suggested potential savings in healthcare costs and reductions in caregiver
      burden. Various degrees of cost savings have been reported depending on the type
      of economic model, treatment evaluated, and region used in the studies. Direct
      comparisons of the results are difficult because different methods have been used
      in these evaluations. The preference of patients and families for home care for
      as long as possible suggests that promoting noninstitutional care for these
      patients should become a priority. Continued home care for patients under
      pharmacological treatment may reduce caregiver burden, healthcare costs, and
      ultimately improve patients' and caregivers' QoL.

PMID- 18044112
TI  - Telomerase confers resistance to caspase-mediated apoptosis.
AB  - There is growing evidence that accelerated telomeric attrition and/or aberrant
      telomerase activity contributes to pathogenesis in a number of diseases.
      Likewise, there is increasing interest to develop new therapies to restore or
      replace dysfunctional cells characterized by short telomeric length using
      telomerase-positive counterparts or stem cells. While telomerase adds telomeric
      repeats de novo contributing to enhanced proliferative capacity and lifespan, it
      may also increase cellular survival by conferring resistance to apoptosis.
      Consequently, we sought to determine the involvement of telomerase for reduced
      apoptosis using ovarian surface epithelial cells. We found that expression of
      hTERT, the catalytic component of telomerase, was sufficient and specific to
      reduce caspase-mediated cellular apoptosis. Further, hTERT expression reduced
      activation of caspases 3, 8, and 9, reduced expression of pro-apoptotic
      mitochondrial proteins t-BID, BAD, and BAX and increased expression of the anti
      apoptotic mitochondrial protein, Bcl-2. The ability of telomerase to suppress
      caspase-mediated apoptosis was p-jnk dependent since abrogation of jnk expression
      with jip abolished resistance to apoptosis. Consequently, these findings indicate
      that telomerase may promote cellular survival in epithelial cells by suppressing
      jnk-dependent caspase-mediated apoptosis.

PMID- 18044113
TI  - Veterans' fall risk profile: a prevalence study.
AB  - The Veterans Health Administration (VHA) serves the health care needs of an
      adult, predominantly male, and aging population. The aging profile of VHA
      patients is 25% greater than the civilian sector (DVA 2001). Aged patients are at
      higher risk for falls. In February 2002, 6 VHA medical centers profiled their
      inpatients' fall risk profile as one aspect of program initiatives targeted at
      reducing veterans' fall risk and fall-related injuries, participating in a one
      day collection of fall risk measurement using the Morse Fall Scale (MFS) for all
      inpatients (n = 1819), acute and long-term care units. Data results are reported
      for age, MFS score, and the relationship between age and score, and by type of
      ward/unit, ie, predominately acute and critical care or long-term care. The
      results of this prevalence study documented that the veteran inpatient population
      are at high-risk for anticipated physiological falls. This Veteran Integrated
      Services Network-wide Deployment of an Evidence-based Program to Prevent Patient
      Falls study was completed as part of a nationally funded clinical initiative,
      National Program Initiative 20-006-1.

PMID- 18044114
TI  - Hypothesized predictors of patient-physician trust and distrust in the elderly:
      implications for health and disease management.
AB  - This study notes the differences between trust and distrust perceptions by the
      elderly as compared with younger populations. Given the importance of trust and
      distrust in compliance, changing behaviors, and forming partnerships for both
      health and disease management, it is necessary to be able to measure patient
      doctor trust and distrust (PDTD). Following recent conceptualizations on trust
      and distrust as coexistent states, this study hypothesizes predictors of PDTD. We
      are proposing that these predictors form the basis for designing, developing and
      validating a PDTD scale (PDTDS). It is important to capture the trust-distrust
      perceptions of older patients as they confront the complexities and
      vulnerabilities of the modem healthcare delivery system. This is necessary if we
      are to design interventions to change behaviors of both the healthcare provider
      and the older patient.

PMID- 18044115
TI  - Comparison of health and effective functioning in Russia and the United States.
AB  - BACKGROUND: Global aging may increase the societal burden of providing more
      resources to augment elders' disabilities. The implications of functional
      disabilities can vary depending on the society in which they occur. OBJECTIVE: To
      determine differences in US and Russian elder citizens' function. RESEARCH
      DESIGN: Convenience sample of persons 60 years and older were surveyed and
      evaluated. SUBJECTS: One hundred community dwelling residents, half from
      Galesburg, Illinois and half from Moscow, Russia. MEASUREMENTS: An interviewer
      administered questionnaire and functional assessment examination. RESULTS: The
      Russian sample was younger than the American sample with a mean age of 67 years
      versus 78 years, and less likely to be widowed or living alone. Sixty percent of
      Russians took no medications compared with 14% of Americans, but Russians
      reported more cardiovascular disease, angina, and hypertension. Forty-four
      percent of Russians screened as being depressed and only 4% of the Americans.
      Self-assessed health was good for 77% of Americans and only 6% of Russians. The
      Medical Outcomes Study SF-36 Health Survey (MOS) eight health concepts showed
      favorable results for the Americans except for physical functioning, which
      indicated no difference. CONCLUSIONS: Marked health and functional differences
      exist between our samples. Russians had more cardiovascular disease, took less
      medication, drank and smoked more and were much more likely to be depressed than
      the US subjects.

PMID- 18044116
TI  - Creativity and the exceptional aging artist.
AB  - Creativity in the aging visual artist is reviewed and modifying factors are
      identified. A program of support for the artist is described with the goal of
      regeneration of career with enhanced creativity and increased productivity.

PMID- 18044117
TI  - Still practicing dentistry at 97.

PMID- 18044118
TI  - 25th anniversary retrospective: experts assess important advances in dentistry.

PMID- 18044119
TI  - Creating hygiene heaven: transform your practice with world-class, patient
      focused service.

PMID- 18044120
TI  - Ensuring optimal success with the Lava system, Part 2: Techno-clinical
      perspectives from authorized Lava Milling Centers.

PMID- 18044121
TI  - Using of bite-wings in the diagnosis of referred pain.

PMID- 18044122
TI  - Audition: a better way to treat and communicate.

PMID- 18044123
TI  - The standard of care for nonsurgical periodontal treatment for reducing the
      dental risk for cardiac disease.

PMID- 18044124
TI  - Achieving form and function for Class II restorations: a simplified technique.

PMID- 18044125
TI  - A new technique for holding indirect restorations.

PMID- 18044126
TI  - Creative uses for a creative curing light.

PMID- 18044127
TI  - Radio microsurgery update: troughing and impression taking.

PMID- 18044129
TI  - High-strength, aesthetic provisional restorations using a bis-acryl composite.

PMID- 18044128
TI  - Dentistry's role in the diagnosis and treatment of obstructive sleep apnea.

PMID- 18044130
TI  - Utilization review and P4P: what dentists need to know.

PMID- 18044131
TI  - Demonstration models: a valuable tool in patient education.

PMID- 18044132
TI  - A six-step plan to a paperless practice.

PMID- 18044133
TI  - Challenges facing age-management/longevity medicine.

PMID- 18044134
TI  - A brief review of moxifloxacin in the treatment of elderly patients with
      community-acquired pneumonia (CAP).
AB  - Community-acquired pneumonia (CAP) remains a common cause of morbidity and a
      potentially life-threatening illness throughout the world mainly in elderly
      patients. Initial antibacterial treatment, usually empirical, should be as
      effective as possible in order to assure rapid clinical resolution and reduce
      high rates of hospitalization and mortality especially affecting aged patients.
      New fluoroquinolones with potent activity against the most important respiratory
      pathogens including Streptococcus pneumoniae, a key pathogen mainly in old
      patients with CAP, have been recently suggested by several international
      guidelines as monotherapy for the treatment of most CAP patient categories. Among
      newer derivatives, moxifloxacin, an advanced generation 8-methoxy quinolone, has
      demonstrated good clinical and bacteriological efficacy in large, well designed
      clinical trials both in adults and old patients with CAP, achieving also in aged
      people efficacy comparable with that of standard treatments. Good pharmacokinetic
      characteristics such as excellent penetration into respiratory tract tissues and
      fluids, optimal bioavailability, simplicity of once-daily dosing, and good
      tolerability, represent potential advantages of moxifloxacin over other
      therapies. In addition, primarily due to a shorter length of hospital stay,
      moxifloxacin has been shown to save costs compared with standard therapy.

PMID- 18044135
TI  - Female pattern hair loss: current treatment concepts.
AB  - Fewer than 45% of women go through life with a full head of hair. Female pattern
      hair loss is the commonest cause of hair loss in women and prevalence increases
      with advancing age. Affected women may experience psychological distress and
      impaired social functioning. In most cases the diagnosis can be made clinically
      and the condition treated medically. While many women using oral antiandrogens
      and topical minoxidil will regrow some hair, early diagnosis and initiation of
      treatment is desirable as these treatments are more effective at arresting
      progression of hair loss than stimulating regrowth. Adjunctive nonpharmacological
      treatment modalities such as counseling, cosmetic camouflage and hair
      transplantation are important measures for some patients. The histology of female
      pattern hair loss is identical to that of male androgenetic alopecia. While the
      clinical pattern of the hair loss differs between men, the response to oral
      antiandrogens suggests that female pattern hair loss is an androgen dependant
      condition, at least in the majority of cases. Female pattern hair loss is a
      chronic progressive condition. All treatments need to be continued to maintain
      the effect. An initial therapeutic response often takes 12 or even 24 months.
      Given this delay, monitoring for treatment effect through clinical photography or
      standardized clinical severity scales is helpful.

PMID- 18044136
TI  - Treating senile dementia with traditional Chinese medicine.
AB  - Senile dementia is a syndrome in the elderly involving deficits in memory and
      cognition. There has been a long history of research and medical practice in
      dementia in China, during which the ancient Chinese people have formed a whole
      theory and accumulated abundant experience in the treatment of dementia. During
      recent decades, with new theories and technologies being digested and integrated,
      progress has been made in the medical and pharmacy research on senile dementia in
      China. In this review, we will focus on the traditional opinion, clinical
      practice, and recent progress in pharmacological research in China towards the
      treatment of dementia. We also discuss the potential trends of global
      convergence.

PMID- 18044137
TI  - Heart failure and cognitive impairment: challenges and opportunities.
AB  - As populations age, heart failure (HF) is becoming increasingly common, and in
      addition to a high burden of morbidity and mortality, HF has an enormous
      financial impact. Though disproportionately affected by HF, the elderly are less
      likely to receive recommended therapies, in part because clinical trials of HF
      therapy have ignored outcomes of importance to this population, including
      impaired cognitive function (ICF). HF is associated with ICF, manifested
      primarily as delirium in hospitalized patients, or as mild cognitive impairment
      or dementia in otherwise stable outpatients. This association is likely the
      result of shared risk factors, as well as perfusion and rheological abnormalities
      that occur in patients with HF. Evidence suggests that these abnormalities may be
      partially reversible with standard HF therapy. The clinical consequences of ICF
      in HF patients are significant. Clinicians should consider becoming familiar with
      screening instruments for ICF, including delirium and dementia, in order to
      identify patients at risk of nonadherence to HF therapy and related adverse
      consequences. Preliminary evidence suggests that optimal HF therapy in elderly
      patients may preserve or even improve cognitive function, though the impact on
      related outcomes remains to be determined.

PMID- 18044139
TI  - Prevention and treatment of venous thromboembolism in the elderly patient.
AB  - Venous thromboembolism (VTE) is a common complication among hospitalized
      patients. Pharmacological thromboprophylaxis has emerged as the cornerstone for
      VTE prevention. As trials on thromboprophylaxis in medical patients have proven
      the efficacy of both low-molecular-weight heparins (LMWHs) and unfractionated
      heparin (UFH), all acutely medical ill patients should be considered for
      pharmacological thromboprophylaxis. Unlike in the surgical setting where the risk
      of associated VTE attributable to surgery is well recognized, and where
      widespread use of pharmacological thromboprophylaxis and early mobilization has
      resulted in significant reductions in the risk of VTE, appropriate VTE
      prophylaxis is under-used in medical patients. Many reasons for this under-use
      have been identified, including low perceived risk of VTE in medical patients,
      absence of optimal tools for risk assessment, heterogeneity of patients and their
      diseases, and fear of bleeding complications. A consistent group among
      hospitalized medical patients is composed of elderly patients with impaired renal
      function, a condition potentially associated with bleeding. How these patients
      should be managed is discussed in this review. Particular attention is devoted to
      LMWHs and fondaparinux and to measures to improve the safety and the efficacy of
      their use.

PMID- 18044140
TI  - A gero-informatics tool to enhance the care of hospitalized older adults with
      cognitive impairment.
AB  - Approximately 50% of hospitalized elders have cognitive impairment (CI) that
      increases their vulnerability to hospital-acquired complications. Matching
      geriatric evaluation and recommendations to the true pace of hospital care may
      improve the care of elders in general, in particular those with CI. Integrating
      information technology into geriatric services (gero-informatics) might allow
      reduction of the time to implementation of geriatric recommendations and prevent
      the initiation of potentially harmful medications and procedures during the
      critical first 48 hours of hospitalization. This paper reviews our local gero
      informatics early experience of developing a computerized decision support system
      (CDSS) to enhance hospital care for elders with CI by reducing inappropriate use
      of anticholinergic medications, urinary catheters, and physical restraints.

PMID- 18044141
TI  - Bone mineral density scans in veterans.
AB  - GOALS: Recent findings suggest the prevalence of osteoporosis among men is under
      recognized. The patient population of the Veterans Health Administration (VA) is
      predominantly male and many elderly veterans may be at risk of osteoporosis.
      Given the lack of data on male osteoporosis, we provide initial insight into
      diagnostic procedures for patients at one VA medical center. PROCEDURES: A review
      and descriptive analysis of patients undergoing radiological evaluation for
      osteoporosis at one VA medical center. RESULTS: We identified 4,919 patients who
      had bone mineral density scans from 2001-2004. VA patients receiving bone mineral
      density scans were commonly white, male, over age 70 and taking medications with
      potential bone-loss side effects. CONCLUSIONS: While further research is needed,
      preliminary evidence suggests that the VA screens the most vulnerable age groups
      in both genders. Heightened awareness among primary care providers of elderly
      male patients at risk of osteoporosis can lead to early intervention and improved
      management of this age-related condition.

PMID- 18044138
TI  - Studies on free radicals, antioxidants, and co-factors.
AB  - The interplay between free radicals, antioxidants, and co-factors is important in
      maintaining health, aging and age-related diseases. Free radicals induce
      oxidative stress, which is balanced by the body's endogenous antioxidant systems
      with an input from co-factors, and by the ingestion of exogenous antioxidants. If
      the generation of free radicals exceeds the protective effects of antioxidants,
      and some co-factors, this can cause oxidative damage which accumulates during the
      life cycle, and has been implicated in aging, and age dependent diseases such as
      cardiovascular disease, cancer, neurodegenerative disorders, and other chronic
      conditions. The life expectancy of the world population is increasing, and it is
      estimated that by 2025, 29% of the world population will be aged > or = 60 years,
      and this will lead to an increase in the number of older people acquiring age
      related chronic diseases. This will place greater financial burden on health
      services and high social cost for individuals and society. In order to acheive
      healthy aging the older people should be encouraged to acquire healthy life
      styles which should include diets rich in antioxidants. The aim of this review is
      to highlight the main themes from studies on free radicals, antioxidants and co
      factors, and to propose an evidence-based strategy for healthy aging.

PMID- 18044142
TI  - Nonpharmacological prevention of osteoporotic fractures.
AB  - Osteoporosis is a systemic, metabolic disease that can result in debilitating
      fractures. The lasting effects of vertebral and hip fractures can cause acute and
      chronic pain, deformity, and emotional distress. Research evidence and clinical
      experience have determined that weight bearing and strength training exercise,
      fall prevention efforts, hip protectors, and some alternative therapies may
      assist patients in avoiding the pervasive and lasting effects of osteoporotic
      fractures. Clinicians should consider the recommendations ofnonpharmacological
      measures to assist patients at risk for experiencing the culminating event of
      this destructive disease.

PMID- 18044143
TI  - Reducing the distance in distance-caregiving by technology innovation.
AB  - Family caregivers are responsible for the home care of over 34 million older
      adults in the United States. For many, the elder family member lives more than an
      hour's distance away. Distance caregiving is a growing alternative to more
      familiar models where: 1) the elder and the family caregiver(s) may reside in the
      same household; or 2) the family caregiver may live nearby but not in the same
      household as the elder. The distance caregiving model involves elders and their
      family caregivers who live at some distance, defined as more than a 60-minute
      commute, from one another. Evidence suggests that distance caregiving is a
      distinct phenomenon, differs substantially from on-site family caregiving, and
      requires additional assistance to support the physical, social, and contextual
      dimensions of the caregiving process. Technology-based assists could virtually
      connect the caregiver and elder and provide strong support that addresses the
      elder's physical, social, cognitive, and/or sensory impairments. Therefore, in
      today's era of high technology, it is surprising that so few affordable
      innovations are being marketed for distance caregiving. This article addresses
      distance caregiving, proposes the use of technology innovation to support
      caregiving, and suggests a research agenda to better inform policy decisions
      related to the unique needs of this situation.

PMID- 18044145
TI  - [Clinical significance of anti-nuclear antibodies in diagnosis of collagen
      diseases].

PMID- 18044144
TI  - [Recent topics on diagnosis and therapy for collagen diseases].

PMID- 18044146
TI  - [Clinical significance of anti-CCP antibody in diagnosis of collagen diseases].

PMID- 18044147
TI  - [Clinical significance of antiphospholipid antibody in diagnosis of collagen
      diseases].

PMID- 18044148
TI  - [Clinical significance of KL-6 and SP-D in diagnosis of collagen diseases].

PMID- 18044149
TI  - [Clinical significance of biomarkers in diagnosis of metabolic bone diseases].

PMID- 18044150
TI  - [Diagnosis and therapy for systemic lupus erythematosus].

PMID- 18044151
TI  - [Diagnosis and therapy for systemic sclerosis].

PMID- 18044152
TI  - [Diagnosis and therapy for polymyositis and dermatomyositis].

PMID- 18044153
TI  - [Diagnosis and therapy for vasculitis].

PMID- 18044154
TI  - [Diagnosis and therapy for rheumatoid arthritis].

PMID- 18044155
TI  - [Diagnosis and therapy for mixed connective tissue diseases].

PMID- 18044157
TI  - [Diagnosis and therapy for adult Still's disease].

PMID- 18044156
TI  - [Diagnosis and therapy for Sjogren syndrome].

PMID- 18044158
TI  - [Diagnosis and therapy for polymyalgia rheumatica].

PMID- 18044160
TI  - [Recent topics on rheumatism and collagen diseases in childhood].

PMID- 18044159
TI  - [Diagnosis and therapy for Behcet disease].

PMID- 18044161
TI  - [Present condition and problems in fibromyalgia].

PMID- 18044162
TI  - [New concept on diagnosis and therapy for rheumatoid and collagen diseases
      (discussion)].

PMID- 18044163
TI  - [Pseudo-thrombocytopenia with uncountable platelets complicated by
      retroperitoneal fibrosis and bleeding symptoms].

PMID- 18044164
TI  - [Temporal arteritis demonstrating a utility of abdominal CT scan in
      identification of aortic involvement].

PMID- 18044165
TI  - [Congenital generalized lipodystrophy with diabetic triopathy].

PMID- 18044166
TI  - [Marked hypoalbuminemia caused by Capillaria philippinensis].

PMID- 18044167
TI  - [Lymphocytic hypophysitis associated with consciousness disturbance due to
      hypernatremia and hypercalcemia].

PMID- 18044168
TI  - [BOOP-like pulmonary lesions preceding polyarteritis nodosa].

PMID- 18044169
TI  - [Complete recovery of central pontine myelinolysis by high dose pulse therapy
      with methylprednisolone].

PMID- 18044170
TI  - [Postpartum acquired hemophilia].

PMID- 18044171
TI  - [Fulminant myocarditis: Cytokines and assisted circulation].

PMID- 18044172
TI  - [Kidney diseases and bone morphogenetic protein].

PMID- 18044173
TI  - [Diagnosis and therapy for multiple myeloma: Practice guidelines].

PMID- 18044174
TI  - [Pitfalls in radiological diagnosis of pulmonary tuberculosis].

PMID- 18044175
TI  - [Clinical path].

PMID- 18044176
TI  - [Application of the Number Needed to Treat to evaluate therapeutic efficacy in
      each patient].

PMID- 18044177
TI  - Developing better therapies through collegial interaction.

PMID- 18044178
TI  - Review of the safety and efficacy of risedronate for the treatment of male
      osteoporosis.
AB  - Osteoporosis in men is an increasingly recognized problem with associated
      fracture morbidity and mortality. Treatment is limited, with the bisphosphonates
      being the mainstay of therapy. Risedronate has demonstrated fracture efficacy in
      women and efficacy has been recently been investigated in men. In men,
      risedronate either maintains or increases bone mineral density. In placebo
      controlled trials it has been shown to be safe and effective in preventing
      fractures.

PMID- 18044180
TI  - Update on bazedoxifene: a novel selective estrogen receptor modulator.
AB  - In the elderly population, osteoporosis is a significant clinical problem leading
      to disability and even death. Many patients remain untreated, despite effective
      therapies, because of patients' unwillingness to take current therapies or
      inability to tolerate the therapies. For this reason, ongoing research continues
      to search for more effective and tolerable osteoporosis agents. Bazedoxifene is a
      selective estrogen receptor modulator (SERM) currently in development for
      osteoporosis prevention and treatment. A new drug application (NDA) for
      postmenopausal osteoporosis prevention was recently submitted to the FDA.
      Preclinical and clinical studies with bazedoxifene demonstrate more tissue
      selectivity than other SERMs. In particular, bazedoxifene has minimal if any
      agonist activity in the uterus and is able to antagonize effects of estrogen on
      the uterus. Animal studies and early clinical studies suggest effects in the bone
      similar to other SERMs with prevention of postmenopausal bone loss. Until more
      data on efficacy and safety are published, however, its role in osteoporosis is
      unknown.

PMID- 18044179
TI  - Effect of estrogens on skin aging and the potential role of SERMs.
AB  - In humans, structural and functional changes attributable to aging are more
      visibly evident in the skin than in any other organ. Estrogens have significant
      effects on skin physiology and modulate epidermal keratinocytes, dermal
      fibroblasts and melanocytes, in addition to skin appendages including the hair
      follicle and the sebaceous gland. Importantly, skin aging can be significantly
      delayed by the administration of estrogen. This paper reviews the effects of
      estrogens on skin and the mechanisms by which estrogens can alleviate the changes
      due to aging that occur in human skin. The relevance of estrogen replacement
      therapy (HRT) in postmenopausal women and the potential value of selective
      estrogen receptor modulators (SERMs) as a therapy for diminishing skin aging are
      also highlighted.

PMID- 18044181
TI  - The osteoporotic male: overlooked and undermanaged?
AB  - Age-related bone loss in men is a poorly understood phenomenon, although
      increasing data on the pathophysiology of bone in men is becoming available. Most
      of what we know on bone pathophysiology derives from studies on women. The well
      known association between menopause and osteoporosis is far from been disproven.
      However, male osteoporosis is a relatively new phenomenon. Its novelty is in part
      compensated for by the number of studies on female osteoporosis and bone
      pathophysiology. On the other hand, the deeper understanding of female
      osteoporosis could lead to an underestimation of this condition in the male
      counterpart. The longer life-span exposes a number of men to the risk of mild-to
      severe hypogonadism which in turn we know to be one of the pathogenetic steps
      toward the loss of bone mineral content in men and in women. Hypogonadism might
      therefore be one among many corrigible risk factors such as cigarette smoking and
      alcohol abuse against which clinicians should act in order to prevent
      osteoporosis and its complications. Treatments with calcium plus vitamin D and
      bisphophonates are widely used in men, when osteoporosis is documented and
      hypogonadism has been excluded. The poor knowledge on male osteoporosis accounts
      for the lack of well shared protocols for the clinical management of the disease.
      This review focuses on the clinical approach and treatment strategy for
      osteoporosis in men with particular attention to its relationship with male
      hypogonadism.

PMID- 18044182
TI  - Eszopiclone for late-life insomnia.
AB  - Insomnia, the most common sleep disturbance in later life, affects 20%-50% of
      older adults. Eszopiclone, a short-acting nonbenzodiazepine hypnotic agent
      developed for the treatment of insomnia, has been available in Europe since 1992
      and in the US since 2005. Although not yet evaluated for transient insomnia in
      older adults, eszopiclone has been shown to be safe and efficacious for short
      term treatment (2 weeks) of chronic, primary insomnia in older adults (64-91
      years). Clinical studies in younger adults (mean = 44 years) have shown
      eszopiclone can be used for 6-12 months without evidence of problems. Because the
      oldest participant in these longer-term trials was 69, it not known whether
      eszopiclone is effective for older adults [particularly the old old (75-84 years)
      and oldest old (85+)] when used over longer periods. This is unfortunate, because
      older individuals frequently suffer from chronic insomnia. Cognitive-behavioral
      therapy for insomnia, which effectively targets the behavioral factors that
      maintain chronic insomnia, represents an attractive treatment alternative or
      adjuvant to eszopiclone for older adults. To date, no studies have compared
      eszopiclone to other hypnotic medications or to nonpharmacological interventions,
      such as cognitive-behavioral therapy for insomnia, in older adults. All of the
      clinical trials reported herein were funded by Sepracor. This paper provides an
      overview of the literature on eszopiclone with special emphasis on its use for
      the treatment of late-life insomnia. Specific topics covered include
      pharmacology, pharmacodynamics, pharmacokinetics, clinical trial data, adverse
      events, drug interactions, tolerance/dependence, and economics/cost
      considerations for older adults.

PMID- 18044183
TI  - Vascular dementia: pharmacological treatment approaches and perspectives.
AB  - Vascular dementia is a common condition for which there are no effective approved
      pharmacological treatments available. Absence of effective treatments creates a
      difficult situation for those suffering from the disease, their caregivers, and
      healthcare providers. This review will address our current understanding of the
      mechanisms of nerve cell damage due to ischemia and summarize available clinical
      trial data on several commonly used compounds including memantine, donepezil,
      galantamine, rivastigmine, nimodipine, hydergine, nicergoline, CDP-choline, folic
      acid, as well as such nonpharmacological approaches as validation therapy.

PMID- 18044184
TI  - Pharmacologic management of overactive bladder.
AB  - Overactive bladder (OAB) is a prevalent and costly condition that can affect any
      age group. Typical symptoms include urinary urgency, frequency, incontinence and
      nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor
      muscle caused by the stimulation of certain muscarinic receptors. Therefore,
      antimuscarinic agents have long been considered the mainstay of pharmacologic
      treatment for OAB. Currently, there are five such agents approved for the
      management of OAB in the United States: oxybutynin, tolterodine, trospium,
      solifenacin and darifenacin. This article summarizes the efficacy,
      contraindications, precautions, dosing and common side effects of these agents.
      All available clinical trials on trospium, solifenacin and darifenacin were
      reviewed to determine its place in therapy.

PMID- 18044186
TI  - The management of hemophilia in elderly patients.
AB  - After the increasing rate of deaths observed during the 1980s due to human
      immunodeficiency virus (HIV) infection, the health-related quality of life and
      life expectancy of persons with hemophilia have improved, mainly due to the
      progresses of replacement therapy and antiviral drugs and to the improvement of
      the global comprehensive care provided by specialized centers. As a consequence,
      an increasing number of hemophiliacs have reached an older age and nowadays
      physicians in hemophilia centers find that they must handle age-related clinical
      problems never previously observed in this population. The management of elderly
      persons with congenital hemophilia is discussed in the first part of this review.
      The second part describes the general aspects of acquired hemophilia due to anti
      factor VIII autoantibodies, focusing on the clinical management of elderly
      patients, one of the groups most frequently affected by this acquired bleeding
      disorder.

PMID- 18044185
TI  - Pathogenesis of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is incredibly common. Increasing longevity ensures its
      prevalence will rise even further. Ongoing efforts to understand AD pathogenesis
      reveal numerous tantalizing leads. Formulating a comprehensive AD pathogenesis
      theory capable of incorporating these disparate leads, though, has proven
      difficult. This review discusses current attempts to formulate a comprehensive AD
      pathogenesis theory. In doing so, it focuses on clinical and molecular
      relationships between AD and aging. A better understanding of these relationships
      could inform and impact future development of AD-directed treatment strategies.

PMID- 18044187
TI  - Use of hyaluronic acid fillers for the treatment of the aging face.
AB  - Hyaluronic acid fillers have become popular soft tissue filler augmentation
      agents over the past several years. They have helped revolutionize the filler
      market with a number of new products available for use for our patients. The
      purpose of this manuscript is to review the characteristics of the HA fillers and
      to review each of the current products currently available for use in the US.

PMID- 18044189
TI  - Osteoporosis screening and risk management.
AB  - Osteoporosis is common among older adults and results in costly osteoporotic
      fractures. Screening for this metabolic bone disorder is warranted in most older
      adults and clinicians must be diligent in identifying persons at risk. The
      evaluation should include an assessment of risk factors for falls, a bone density
      test, and consideration of possible secondary causes of osteoporosis. Several
      medications are available to improve bone density and decrease fractures.
      Adequate calcium and vitamin D intake (and treatment of vitamin D deficiency) are
      paramount in the management of osteoporosis.

PMID- 18044188
TI  - Effects of antioxidant supplementation on the aging process.
AB  - The free radical theory of aging hypothesizes that oxygen-derived free radicals
      are responsible for the age-related damage at the cellular and tissue levels. In
      a normal situation, a balanced-equilibrium exists among oxidants, antioxidants
      and biomolecules. Excess generation of free radicals may overwhelm natural
      cellular antioxidant defences leading to oxidation and further contributing to
      cellular functional impairment. The identification of free radical reactions as
      promoters of the aging process implies that interventions aimed at limiting or
      inhibiting them should be able to reduce the rate of formation of aging changes
      with a consequent reduction of the aging rate and disease pathogenesis. Even if
      antioxidant supplementation is receiving growing attention and is increasingly
      adopted in Western countries, supporting evidence is still scarce and equivocal.
      Major limitations in literature are still needed to be addressed to better
      evaluate the potential benefits from antioxidant supplementation: 1) an improved
      understanding of oxidation mechanisms possibly at the basis of the aging process,
      2) the determination of reliable markers of oxidative damage and antioxidant
      status, 3) the identification of a therapeutic window in which an eventual
      antioxidant supplementation may be beneficial, 4) a deeper knowledge of the
      antioxidant molecules which in several conditions act as pro-oxidants. In the
      present paper, after a preliminary introduction to the free radical theory of
      aging and the rationale of antioxidant supplementation as an anti-aging
      intervention, we will present an overview of evidence relating antioxidant
      supplementations with clinical conditions typical of older age (ie,
      cardiovascular disease, Alzheimer's disease, cancer). We will also discuss
      studies that have evaluated whether antioxidant supplementation might improve
      major outcomes of interest in older persons (ie, physical performance, muscle
      strength, longevity). Given the large amount of data available on the antioxidant
      supplementation topic, this overview is not intended to be exhaustive. The aim of
      this paper is to provide the main basis from which future studies should start
      and indicate which the main limitations that need to be addressed are.

PMID- 18044190
TI  - Discharge destination from an acute care for the elderly (ACE) unit.
AB  - Older adults age 65 and over account for a disproportional number of hospital
      stays and discharges compared to other age groups. The objective of this paper is
      to describe placement and characteristics of older patients discharged from an
      acute care for the elderly (ACE) unit. The study sample consists of 1,351 men and
      women aged 65 years or older that were discharged from the ACE Unit during a 12
      month period. The mean number of discharges per month was 109.2 +/- 28.4. Most of
      the subjects were discharged home or home with home health 841, 62.3%. The oldest
      elderly and patients who had been admitted from long-term care institutions or
      from skilled nursing facilities to the ACE unit were less likely to return to
      home.

PMID- 18044191
TI  - The aging process and potential interventions to extend life expectancy.
AB  - Aging is commonly defined as the accumulation of diverse deleterious changes
      occurring in cells and tissues with advancing age that are responsible for the
      increased risk of disease and death. The major theories of aging are all specific
      of a particular cause of aging, providing useful and important insights for the
      understanding of age-related physiological changes. However, a global view of
      them is needed when debating of a process which is still obscure in some of its
      aspects. In this context, the search for a single cause of aging has recently
      been replaced by the view of aging as an extremely complex, multifactorial
      process. Therefore, the different theories of aging should not be considered as
      mutually exclusive, but complementary of others in the explanation of some or all
      the features of the normal aging process. To date, no convincing evidence showing
      the administration of existing "anti-aging" remedies can slow aging or increase
      longevity in humans is available. Nevertheless, several studies on animal models
      have shown that aging rates and life expectancy can be modified. The present
      review provides an overlook of the most commonly accepted theories of aging,
      providing current evidence of those interventions aimed at modifying the aging
      process.

PMID- 18044193
TI  - Health benefits of Tai Chi for older patients with type 2 diabetes: the "Move It
      For Diabetes study"--a randomized controlled trial.
AB  - Older adults with type 2 diabetes have mobility impairment and reduced fitness.
      This study aimed to test the efficacy of the "Tai Chi for Diabetes" form,
      developed to address health-related problems in diabetes, including mobility and
      physical function. Thirty-eight older adults with stable type 2 diabetes were
      randomized to Tai Chi or sham exercise, twice a week for 16 weeks. Outcomes
      included gait, balance, musculoskeletal and cardiovascular fitness, self-reported
      activity and quality of life. Static and dynamic balance index (-5.8 +/- 14.2; p
      = 0.03) and maximal gait speed (6.2 +/- 11.6%; p = 0.005) improved over time,
      with no significant group effects. There were no changes in other measures. Non
      specific effects of exercise testing and/or study participation such as outcome
      expectation, socialization, the Hawthorne effect, or unmeasured changes in health
      status or compliance with medical treatment may underlie the modest improvements
      in gait and balance observed in this sham-exercise-controlled trial. This Tai Chi
      form, although developed specifically for diabetes, may not have been of
      sufficient intensity, frequency, or duration to effect positive changes in many
      aspects of physiology or health status relevant to older people with diabetes.

PMID- 18044192
TI  - Factors that influence exercise activity among women post hip fracture
      participating in the Exercise Plus Program.
AB  - Using a social ecological model, this paper describes selected intra- and
      interpersonal factors that influence exercise behavior in women post hip fracture
      who participated in the Exercise Plus Program. Model testing of factors that
      influence exercise behavior at 2, 6 and 12 months post hip fracture was done. The
      full model hypothesized that demographic variables; cognitive, affective,
      physical and functional status; pain; fear of falling; social support for
      exercise, and exposure to the Exercise Plus Program would influence self
      efficacy, outcome expectations, and stage of change both directly and indirectly
      influencing total time spent exercising. Two hundred and nine female hip fracture
      patients (age 81.0 +/- 6.9), the majority of whom were Caucasian (97%),
      participated in this study. The three predictive models tested across the 12
      month recovery trajectory suggest that somewhat different factors may influence
      exercise over the recovery period and the models explained 8 to 21% of the
      variance in time spent exercising. To optimize exercise activity post hip
      fracture, older adults should be helped to realistically assess their self
      efficacy and outcome expectations related to exercise, health care providers and
      friends/peers should be encouraged to reinforce the positive benefits of exercise
      post hip fracture, and fear of falling should be addressed throughout the entire
      hip fracture recovery trajectory.

PMID- 18044194
TI  - Patterns of intimate partner homicide suicide in later life: strategies for
      prevention.
AB  - Intimate partner homicide suicide (IPHS) constitutes the most violent domestic
      abuse outcome, devastating individuals, families, neighborhoods and communities.
      This research used content analysis to analyze 225 murder suicide events (444
      deaths) among dyads with at least one member 60 or older. Data were collected
      from newspaper articles, television news transcripts, police reports and
      obituaries published between 1999 and 2005. Findings suggest the most dangerous
      setting was the home and the majority of perpetrators were men. Firearms were
      most often employed in the violence. Relationship strife was present in some
      cases, but only slightly higher than the divorce rate for that age group. Illness
      was cited in just over half of the cases, but 30% of sick elderly couples had
      only a perpetrator who was ill. Evidence of suicide pacts and mercy killings were
      very rare and practitioners are encouraged to properly investigate these events.
      Suicidal men in this age range must be recognized as a potential threat to
      others, primarily their partner. Homicide was sometimes the primary motive, and
      the perpetrators in those cases resembled the "intimate terrorist." Victims in
      those cases were often terrorized before the murder. Clinicians are educated
      about the patterns of fatal violence in later life dyads and provided with
      strategies for prevention.

PMID- 18044196
TI  - Treatment of specific phobia in older adults.
AB  - Phobias are common in later life, yet treatment research in this population
      remains scant. The efficacy of exposure therapy, in combination with other
      Cognitive-Behavioral Therapy (CBT) components, in the treatment of specific
      phobia with a middle and older aged sample was examined. Sixteen adults aged 45
      68 with DSM-IV diagnosis of a specific phobia received a manualized intervention
      over ten weeks, and were compared with a control group. Results indicated
      significant time effects in the treatment group for the primary outcome variables
      of phobic severity and avoidance as well as secondary outcome variables including
      depression and anxiety. Symptom presence and severity also significantly declined
      in the treatment group. No significant changes in state anxiety were noted across
      the treatment period. Such results provide support for the efficacy of exposure
      combined with CBT treatment for specific phobia in middle to older aged adults.

PMID- 18044197
TI  - Effects of intergenerational Montessori-based activities programming on
      engagement of nursing home residents with dementia.
AB  - Fourteen nursing home residents on a dementia special care unit at a skilled
      nursing facility took part in one-to-one intergenerational programming (IGP) with
      15 preschool children from the facility's on-site child care center. Montessori
      based activities served as the interface for interactions between dyads. The
      amount of time residents demonstrated positive and negative forms of engagement
      during IGP and standard activities programming was assessed through direct
      observation using a tool developed for this purpose--the Myers Research Institute
      Engagement Scale (MRI-ES). These residents with dementia displayed the ability to
      successfully take part in IGP. Most successfully presented "lessons" to the
      children in their dyads, similar to the way that Montessori teachers present
      lessons to children, while persons with more severe cognitive impairment took
      part in IGP through other methods such as parallel play. Taking part in IGP was
      consistently related with higher levels of positive engagement and lower levels
      of negative forms of engagement in these residents with dementia than levels seen
      in standard activities programming on the unit. Implications of using this form
      of IGP, and directions for future research, are discussed.

PMID- 18044195
TI  - The therapeutic effects of the physician-older patient relationship: effective
      communication with vulnerable older patients.
AB  - There is growing evidence that the outcomes of health care for seniors are
      dependent not only upon patients' physical health status and the administration
      of care for their biomedical needs, but also upon care for patients' psychosocial
      needs and attention to their social, economic, cultural, and psychological
      vulnerabilities. Even when older patients have appropriate access to medical
      services, they also need effective and empathic communication as an essential
      part of their treatment. Older patients who are socially isolated, emotionally
      vulnerable, and economically disadvantaged are particularly in need of the
      social, emotional, and practical support that sensitive provider-patient
      communication can provide. In this review paper, we examine the complexities of
      communication between physicians and their older patients, and consider some of
      the particular challenges that manifest in providers' interactions with their
      older patients, particularly those who are socially isolated, suffering from
      depression, or of minority status or low income. This review offers guidelines
      for improved physician-older patient communication in medical practice, and
      examines interventions to coordinate care for older patients on multiple
      dimensions of a biopsychosocial model of health care.

PMID- 18044199
TI  - [Clinical and electrophysiological findings in carpal tunnel syndrome].
AB  - Carpal tunnel syndrome (CTS) is the most common nerve entrapment disorder. The
      clinical features of CTS are variable, but usually include pain and paresthesia
      in the thumb, first two fingers, and the radial-half of the ring finger.
      Paresthesia and sensory deficits might involve the entire palm area in some
      cases. Pain frequently radiate proximally into the forearm, and occasionally to
      the shoulder. Many patients experience pain at night and are awakened by abnormal
      sensations. Shaking hand relief the symptom. The two classic tests for nerve
      compression at the wrist are the Tinel test and the Phalen maneuver, which
      diagnostic value is limited. Golden standard for the diagnosis is the combination
      of the clinical findings and the electrophysiological study. Routine median nerve
      conduction study is valuable. Prolonged terminal latency of motor or sensory
      nerve would be found in most CTS hands. If the routine study showed equivocal,
      more sensitive methods are needed. Those include segmental sensory conduction
      study across the carpal tunnel by median stimulation at midpalm, a comparison of
      median and ulnar sensory nerve latencies at ring finger and a comparison of
      median and radial sensory nerve latencies at thumb. A difference between the
      median motor latency to the second lumbrical and the ulnar motor latency to the
      interossei muscles has also diagnostic value in some cases. In addition, inching
      method can localized the compression site. Using these techniques, the diagnosis
      of CTS would become more reliable.

PMID- 18044198
TI  - Predictors of adherence to physical activity in the Lifestyle Interventions and
      Independence for Elders pilot study (LIFE-P).
AB  - OBJECTIVES: A prospective design was used to examine predictors of adherence to a
      physical activity intervention in older adults with compromised function.
      METHODS: The sample included 213 men (31.1%) and women (68.9%) with an average
      age of 76.53 years. RESULTS: The predictor variables accounted for 10% of the
      variance in percent attendance during adoption and transition, respectively.
      Adding percent attendance during adoption to the prediction of percent attendance
      during transition increased the explained variance in this phase to 21%. During
      maintenance, the predictors accounted for 13% of the variance in frequency of
      physical activity; this estimate increased to 46% when adding in percent
      attendance from the transition phase. DISCUSSION: These results are encouraging
      in that the physical activity intervention appears to have been well tolerated by
      diverse subgroups of older adults. The role of prior behavior in predicting
      downstream adherence underscores the importance of developing proactive
      interventions for treating nonadherence in older adult populations.

PMID- 18044200
TI  - [Operative treatment for carpal tunnel syndrome].
AB  - Carpal tunnel syndrome is an entrapment neuropathy where the median nerve is
      compressed inside of the carpal canal. Causes of this syndrome include repetitive
      strain, wrist fracture, rheumatoid arthritis, space-occupying lesion, dialysis
      related amyloidosis, diabetes mellitus, and in addition, cases with no apparent
      cause. Similar symptoms such as numbness, sensory disturbance of the median nerve
      distribution area and weakness of thenar muscles also occur in patients who
      suffer from cervical diseases. In cases where the patient suffers from both
      carpal tunnel syndrome and cervical disease, the patient's complaints may not
      disappear if treatment is only performed for one of them. Therefore, accurate
      diagnosis of the cause of the symptoms, using electrophysiological test results
      and/or carpal canal pressure measurement results is essential to the successful
      treatment of such patients. The purpose of operative treatments for carpal tunnel
      syndrome is to decompress the median nerve. A variety of operative treatment
      techniques, i.e., standard open procedure, minimum incision open procedure, one
      portal or two-portal endoscopic procedures, etc., are used. Every procedure has
      different conditions such as equipment used, operative hand positions, location
      and size of skin incisions, blind ways or no blind ways, approaches to target
      tissues, tourniquet usage and others. I developed the world's first endoscopic
      operative procedure for carpal tunnel syndrome using the Universal Subcutaneous
      Endoscope (USE) system in 1986 and I have operated on over 7,300 hands during
      these last 20 years. My technique has been proven by pre- and postoperative
      carpal canal pressure and intraneural median nerve pressure measurement results
      as an evidence-based medicine. Before an operative method is chosen, the most
      important thing to consider is whether or not it will safely and completely
      achieve the purpose as evidence-based medicine with minimal invasion of the
      patient.

PMID- 18044201
TI  - [Occupation and carpal tunnel syndrome].
AB  - Carpal tunnel syndrome (CTS), compression of the median nerve at the carpal
      tunnel of the wrist, is the most common of all entrapment syndromes. Diabetes,
      Rheumatoid arthritis, hypothyroidism and pregnancy are known to cause CTS. And
      certain occupations were been reported the risk factor of CTS. We report two
      patients with occupationally induced CTS, and discuss the relation between the
      development of CTS and occupation with reference to previous papers. Occupations
      that appear to promote CTS were classified in to three groups: jobs entailing the
      use of vibratory tools, assembly work and food processing and packing. These
      occupations involved repeated flexion and extension of the wrist. The prevalence
      of CTS was related to not only repetitive work but also forceful work involving
      the wrist. Both occupational and non-occupational factors (gender, age, body mass
      index, thyroid function and diabetes mellitus) were considered risk factors for
      CTS. The prevalence of CTS in Visual Display Terminal (VDT) workers was not high
      compared to that in control groups. If the cause of CTS is considered to be due
      to an occupational factor, the patient would be eligible workmen's compensation,
      and should be suspended from work as soon as possible. It has been reported that
      assembly line workers showed resolution of symptoms and normal nerve conduction
      studies after 2 years of a reduced work schedule. Treatment for CTS should begin
      early. When these workers return to work, the environment and the condition of
      work should be improved to prevent recurrence.

PMID- 18044202
TI  - [Management of carpal tunnel syndrome--"bread and butter" in the United States].
AB  - In the United States, carpal tunnel syndrome (CTS) is one of the most common
      diseases and is well recognized by the general population. The number and amount
      of workers' compensation claims in the U.S. are enormous and the news has been
      received high degree of attention. Similar to Japan, the initial treatment is non
      surgical, but the failure to non-surgical treatment usually leads to surgical
      intervention without delay.

PMID- 18044203
TI  - [DARPP-32 in the patients with endogenous psychosis].
AB  - Dopamine- and cyclic AMP-regulated phosphoprotein with a relative molecular
      weight of 32 kDa (DARPP-32) plays an important role in integrating information of
      about several neurotransmitters arriving at dopaminoceptive neurons. DARPP-32 is
      phosphorylated by dopamine D1 receptor at threonine 34 and converted to an
      inhibitor of protein phosphatase I. It facilitates the phosphorylation of several
      neurotransmitter receptors, including N-methyl-D-aspartic acid (NMDA)- and alpha
      amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA)-type glutamate receptors
      and gamma-aminobutyric acid (GABA)A receptors. In contrast, D2 receptor
      stimulation induces dephosphorylation of DARPP-32, which results in
      dephosphorylation of the glutamate and GABAA receptors. Thus, phosphorylation and
      dephosphorylation of DARPP-32 regulates the functions of neurotransmitter
      systems. Recent studies from our laboratory and elsewhere have demonstrated that
      the amount of DARPP-32 in the dorsolateral prefrontal cortex (DLPFC) of subjects
      with schizophrenia is lower than that in the DLPFC of control subjects. Thus, it
      is plausible that DARPP-32 is associated with the concurrent alterations in
      dopamine, glutamate, and GABA neurotransmitter systems in subjects with
      schizophrenia. We have also found reduced levels of DARPP-32 in the DLPFC of
      subjects with bipolar disorder. Thus, it is important to elucidate the role of
      DARPP-32 in the pathophysiology of schizophrenia and bipolar disorder.

PMID- 18044204
TI  - [Demographic characteristics of RBD patients at a sleep center--with special
      emphasis on neurodegenerative diseases as the background condition].
AB  - REM sleep behavior disorder (RBD) is characterized by loss of normal REM sleep
      skeletal muscle atonia, resulting in complex motor behaviors associated with
      dream mentation. Reports have been accumulated showing an association of RBD and
      neurodegenerative diseases. However, in Japan, no data has been available about
      demographic features of RBD in a large patient population. We describe
      demographic characteristics of RBD patients presenting to our sleep center with
      special emphasis on association of RBD and neurodegenerative diseases. METHODS:
      The subjects were consecutive 10,745 patients who presented with sleep and/or
      wake problems at our sleep center from April 1998 to March 2006. Diagnosis of RBD
      was made based on ICSD-2 criteria. Medical and sleep histories with complementary
      information from family members, and findings of neurological examination were
      assessed retrospectively from the notes of RBD patients. RESULTS: Sixty-seven
      patients (0.6%) were diagnosed as having RBD. There was strong male predominancy
      (85.1%). The onset of RBD symptoms was at 61.4+/-8.8 years of age. Neurological
      symptoms and signs were present in twelve (17.9 % of RBD patients) when they
      firstly came to our sleep center: 4 patients with Parkinson disease, 4 with
      multiple system atrophy and 1 with probable dementia with Lewy body. Thirteen
      patients (43.3%) were aware of olfactory impairment when inquired (out of 30
      patients). Clonazepam was administered in 29 patients, and 21 (72.4%) responded
      well. CONCLUSION: Our study showed the similar demographic characteristics of RBD
      to what was shown in the previous large case series. Although the association
      between RBD and neurodegenerative diseases was not so strong in our cases, it may
      be mainly because our sleep center was not run in the domain of neurology
      department and we could not vigorously detect the possible coexistence of
      neurodegenerative disease. The pathogenesis of RBD is still unclear; therefore,
      neurologists and sleep specialists need to collaborate in following up RBD
      patients to confirm whether they are at higher risk for developing a
      neurodegenerative disease.

PMID- 18044205
TI  - [A case of brainstem encephalitis following multiple cranial neuropathy in a
      hepatocellular carcinoma patient--association with cytomegalovirus and varicella
      zoster virus infection].
AB  - A 72-year-old male with liver cirrhosis and hepatocellular carcinoma experienced
      general fatigue. Four days later he was admitted to our hospital because of
      dizziness, dysbasia and left facial palsy (day 1). On day 6, a neurological
      examination revealed left trigeminal neuralgia, left medial longitudinal
      fasciculus (MLF) syndrome, skew deviation, hypacusia, tongue deviation and left
      limb ataxia. Magnetic resonance imaging of the brain including diffusion-weighted
      imaging showed previous lacunar infarctions at the left thalamus and pons. The
      immunological investigation for viral infection in his serum samples showed high
      titers of IgM antibody against cytomegalovirus (CMV). Cerebrospinal fluid (CSF)
      investigation revealed mononuclear pleocytosis, elevated protein levels and high
      titers of IgG antibody against the varicella-zoster virus (VZV). Anti-CMV
      antibody measurement and CMV-DNA detection by the polymerase chain reaction in
      CSF revealed that the central nervous system (CNS) was not infected by CMV. We
      diagnosed this case as brainstem encephalitis following multiple cranial
      neuropathy associated with CMV and VZV infections. The neurological symptoms
      gradually improved with aciclovir and prednisolone therapy. The titers of
      antibody for CMV in his serum samples normalized 4 months later after onset.
      Although there was no evidence of CMV infection in the CNS was obtained,
      parainfection or autoimmune mediated responses followed by viral infections might
      have led to brainstem encephalitis with multiple cranial nerve involvements in
      our patient.

PMID- 18044206
TI  - [A case of acute mountain sickness followed by globus pallidus syndrome].
AB  - A 71-year-old female was suffered from acute mountain sickness at an altitude of
      about 3,700 m. and became comatose. Although the patient recovered from the
      symptom after coming down from the mountain, family members and friends began to
      notice her personality changes in daily life. She became apathetic,
      uncommunicative, expressionless, less interested in hobbies and less sociable and
      was pointed it out by them. In neurological images, MRI revealed localized
      lesions at the globus pallidus, bilaterally. It was conjectured that pallidal
      lesions caused by hypobaric hypoxia at high elevation in the case induced
      neurobehavioral syndrome (globus pallidus syndrome) similar to the frontal lobe
      syndrome by way of the frontal-subcortical circuits. As, in recent years, the
      transportation to high ground has become relatively easy for the elderly, it is
      feared that the incidence of acute mountain sickness may increase. In acute
      mountain sickness, while neurological symptoms at the acute phase, such as
      headache, consciousness disturbances and ataxia, are emphasized, it is necessary,
      in examination of patients who recovered from acute symptoms, to recognize the
      presence of executive dysfunction as aftereffect, as seen in the present case.

PMID- 18044207
TI  - [Acute urinary retention secondary to aseptic meningoencephalitis in an infant-
      case report].
AB  - We report the case of a 21-month-old boy with urinary retention secondary to
      aseptic meningitis. After high fever for 10 days, appetite loss, somnolence,
      acute transient urinary retention, constipation and mild dysesthesia in bilateral
      lower limbs developed. Brisk reflexes were present in the lower extremities along
      with a positive Babinski reflex. Cerebrospinal fluid (CSF) examination revealed
      mild mononuclear cell-dominant pleocytosis. Human herpes virus (HHV)-6 was not
      detected in the CSF by polymerase chain reaction (PCR) analysis; however, it was
      detected in the throat, plasma, and mononuclear cells of the peripheral blood.
      Virus-specific immunoglobulin M antibodies against HHV-6 were not detected by
      enzyme immunoassay. Brain magnetic resonance imaging (MRI) yielded normal
      results; however, T1-weighted MRI of the conus terminalis with contrast
      enhancement showed region of high intensity from the lower thoracic to lumbar
      meninges. In T2-weighted imaging, slight hyperintensity was observed in the
      lumbar spinal cord without enhancement effect. The catheter was removed 1 week
      after high-dose intravenous methyl-prednisolone treatment and the patient was
      able to walk 3 weeks later without any sequelae. Vesicorectal disturbance and the
      neurological symptoms observed in aseptic meningitis were similar to those of HSV
      type 2-induced lumbosacral meningo-radiculitis, designated as Elsberg syndrome or
      meningitis-retention syndrome in adults. The recurrence of HHV-6 might be
      immunologically related to this meningitis-retention syndrome based on the
      results of PCR analysis and enzyme immunoassay for virus-specific antibodies.
      Several reports have described lumbosacral meningo-radiculitis in adults and
      older children, but this appears to be particularly rare in infants.

PMID- 18044208
TI  - [Growing skullbase fracture--a case report with special reference to its
      pathogenesis].
AB  - This report describes a growing skullbase fracture in a six-year-old girl. She
      had a history of anterior skullbase fracture three years previously and
      meningitis two years later. She was referred to our hospital because of bacterial
      meningoencephalitis. Neuroimaging disclosed a bone defect and meningocele at the
      same site as the previous fracture. Although a growing skull fracture of the
      anterior cranial base is extremely rare, the reported cases include not only
      pediatric patients but also adults. Furthermore, posttraumatic pseudo-meningocele
      or encephalocele can be considered to be part of the same entity as growing
      skullbase fracture. Therefore, "weakness of surrounding tissue" seems to be
      another important factor as well as "the expanding force of the growing brain"
      and "dural tear", which are well-known to be essential in the growth of a
      fracture. Since a growing fracture at the anterior skullbase is difficult to
      identify from the outside, it is very important to follow-up changes in the
      fracture line from the acute stage of injury.

PMID- 18044209
TI  - [An autopsied case of adult T-cell leukemia/lymphoma (ATLL) presenting with
      specific MRI findings in the cerebral cortex].

PMID- 18044210
TI  - [One hundred books which built up neurology (11)].

PMID- 18044211
TI  - [Problem of illegal drugs in Japan].

PMID- 18044212
TI  - [Standardized treatment of acute intoxication--present state in Japan].

PMID- 18044213
TI  - [Survey on the initial management of acute poisoning in Japan].

PMID- 18044214
TI  - [Gastric lavage].

PMID- 18044215
TI  - [Whole bowel irrigation].

PMID- 18044216
TI  - [Do you know the Practice Guideline of Japanese Society for Clinical Toxicology?
      Do you seek consent from patients?].

PMID- 18044217
TI  - [Activated charcoal].

PMID- 18044218
TI  - [Forced diuresis].

PMID- 18044219
TI  - [Clinical analysis of 104 cases of overdose in suicide attempts].
AB  - Patients who have attempted suicide by taking medicines are frequently admitted
      to emergency and critical care medical centers. These patients usually have both
      physical and mental problems. Some try repeatedly to commit suicide. In this
      study, to ascertain how to prevent repeated attempts of suicide, we investigated
      the clinical characteristics of patients attempting suicide by taking overdoses
      of medicine. One hundred and four cases of suicide attempted by taking an
      overdose of medicine, seen at The Emergency and Critical Care Medical Center,
      Tottori University Hospital, Tottori from April 2005 to March 2006, were
      investigated in this retrospective study. Patients were 25 males (24%), and 79
      females (76%). Eighty one patients (77.9%) had regularly been receiving
      psychiatric care, with neurotic disorders being the most common psychiatric
      condition. Thirty eight patients (36.5%) had repeated suicide attempts by taking
      an overdose of medicine. In 2005, there were 9 patients (9.4%) who had repeatedly
      consulted our critical care medical center. Most of these patients were females
      who had previously consulted a psychiatric clinic and had diagnoses of stress
      related or personality disorders. In this study, we demonstrated that it is
      important to build a good relationship between psychiatrists and emergency
      doctors. As well, to prevent repeated incidents of taking an overdose of
      medicines in a suicide attempt, it is important to ensure that medical and
      psychosocial support are positively applied to patients with such tendencies.

PMID- 18044220
TI  - [Autopsy case of aspirin intoxication: distribution of salicylic acid and
      salicyluric acid in body fluid and organs].
AB  - A 52 year-old woman ingested approximately 300 tablets (325 mg) of aspirin in a
      suicide attempt. We analyzed the concentrations of salicylic acid (SA) and
      salicyluric acid (SUA) in body fluids and organs using a modified previous high
      performance liquid chromatographic method. The concentrations of SA in heart and
      femoral blood were 1.1 mg/mL and 1.3 mg/mL, respectively; the results were far
      higher than the lethal level. The concentration of SA was 0.3-0.4 mg/g in brain,
      0.9-1.4 mg/g in lung, 0.6-0.8 mg/g in liver and 0.9 mg/mL in kidney.

PMID- 18044221
TI  - [Delayed neuropsychologic sequelae of carbon monoxide poisoning].

PMID- 18044222
TI  - [Worry of health damage by lead in metal accessories and analogous products].

PMID- 18044223
TI  - [Epilepsy surgery and focus detection utilizing imaging of preoperative multi
      modal examinations].

PMID- 18044224
TI  - [Minimally invasive anterior interhemispheric lamina terminalis approach for
      craniopharyngiomas. Anatomical, hormonal, and neuropsychological considerations].

PMID- 18044225
TI  - [Management of chiasmatic-hypothalamic gliomas in children: report of nine
      pediatric cases].
AB  - Radical resection of chiasmatic-hypothalamic glioma (CHG) carries a significant
      risk of morbidity and the optimum treatment remains undecided. The authors
      reported 9 children with CHG, who were treated with surgical resection with or
      without postoperative chemotherapy. Age at the time of diagnosis ranged from 4
      months to 7.7 years (mean 3.1 years), and no patient had evidence of
      neurofibromatosis type 1. Surgical resections of the tumors were performed in all
      patients because of severe visual impairment or intracranial hypertension caused
      by large tumors. All of the surgical interventions resulted in partial
      resections. Pathological examination revealed pilocytic astrocytomas in 7
      patients, low grade astrocytoma in 1 and anaplastic astrocytoma in 1. Seven
      patients with residual tumors received postoperative chemotherapy consisting of
      cisplatin, cyclophosphamide, etoposide and vincristine. Reduction in tumor size
      was noticed in 5 patients, although 2 patients had no response and switched to
      local radiotherapy. Although minor complications of chemotherapy were noticed in
      5 patients, severe sequelae such as neuropsychological deficits or
      endocrinopathies did not occur, and all patients completed chemotherapy programs.
      Additional treatments are recommended in case of incomplete tumor resections,
      because our experience demonstrates that the majority of the residual tumors have
      potential to progress. Our present data suggests that the chemotherapy of the
      aforementioned regimen is effective in controlling CHGs after partial resections
      and is relatively well tolerated even in young children who are vulnerable to
      radiotherapy.

PMID- 18044227
TI  - [Intracranial internal carotid artery aneurysm associated with extracranial
      occlusion of the ipsilateral internal carotid artery in a patient with polycystic
      kidney disease].
AB  - We report a rare case with polycystic kidney disease (PKD) having an intracranial
      internal carotid artery aneurysm associated with extracranial occlusion of the
      ipsilateral internal carotid artery. A 55-year-old man with chronic renal failure
      due to PKD presented with headache. CT scan and MRI showed no abnormal findings.
      MRA showed cervical occlusion of the right internal carotid artery and an
      ipsilateral intracranial carotid aneurysm. At surgery, the saccular aneurysm
      protruded anterolaterally at the C2 portion of the right internal carotid and was
      clipped. Hemodynamic stress of the blood flow through the posterior communicating
      artery and the fragility of arteries because of PKD were considered to be two
      main causes of aneurysmal formation in this case.

PMID- 18044226
TI  - [The utility of presurgical simulation of microvascular decompression by MR
      virtual endoscopy].
AB  - OBJECTIVE: We conducted the present study to assess the utility of virtual
      endoscopy (VE) created by volume rendering of MR images in presurgical simulation
      for trigeminal neuralgia (TN) and hemifacial spasm (HFS). METHODS: In 12 patients
      (six with TN and six with HFS), we presurgically evaluated the anatomy of the
      cerebellopontine angle (CPA) region and simulated an appropriate surgical
      approach by VE of heavy T2-weighted imaging and MR angiography. RESULTS: The
      three-dimensional (3-D) relations of neurovascular structures in the CPA region
      were compatible between on-VE and on-the-intraoperative view in all patients. The
      compression sites and the major offending vessels were correctly depicted, except
      for two small branches as the offending vessel. The other important structures
      affecting the surgical procedure were identified as major petrosal veins in all
      patients with TN, a vertebral artery in three with HFS, and a large cerebellar
      flocculus in three with HFS. Transposition of the offending vessels was performed
      as simulated in all patients with TN and in three patients with HFS. All patients
      had an excellent surgical outcome. CONCLUSIONS: Presurgical simulation by VE in
      patients with TN and HFS is a novel method that provides excellent visualization
      of the 3-D relations of neurovascular structures in the CPA region and allows us
      to accomplish successful and safe surgery.

PMID- 18044228
TI  - [A case report of arteriovenous malformation of the tongue: vascular anatomy and
      note for transarterial embolization].
AB  - Arteriovenous malformation (AVM) of the tongue is a rare lesion of the cranio
      facial vascular anomaly. Decision making concerning the vascular anomaly is not
      established because there are complex classifications of diagnosis and many
      treatment options. We report a case of AVM of the tongue, and review vascular
      anatomy and knowledge for treating this lesion. A 50-year-old man presented with
      dysarthria, sleep apnea and snoring because of a mass lesion of his sublingual
      region that had become larger over a two-year period. Neuroradiological
      examination revealed lingual arteriovenous fistula (AVF) associated with AVM of
      the tongue base. We performed transfemoral transarterial embolization via both
      lingual arteries using Polyvinyl alcohol particles and Eudragit-E as non-adhesive
      glue material. Final angiograms after embolization revealed a small residual
      nidus fed by the right facial artery mental branch, but shunt flow was markedly
      reduced. This vascular malformation was removed after a day of TAE (transarterial
      embolization). The patients symptom was improved and relapse has not been
      confirmed though 18 months have passed since the surgery. Using classification
      proposed by Mulliken and Glowacki, vascular anomalies are divided into two
      groups: hemangiomas and vascular malformations (AVM/F, arterial, venous,
      capillary, lymphatic and combined). AVM/F is classified into high flow
      malformation. TAE is useful for high flow malformation and can be used as the
      sole treatment or as an adjunct. Treatment should be to eradicate nidus or
      fistula completely, which is the fundamental abnormality because even the
      smallest residual nidus will expand to cause recurrence. The treatment of Cranio
      facial AVM's requires rigorous differential diagnosis and appropriate management.
      Inadequate treatment is thought to contribute to collateral flow and disease
      progression in advanced AVM, making further management difficult.

PMID- 18044229
TI  - [A case of spontaneous fusiform aneurysm in a middle cerebral artery branch which
      causes rapidly thrombosed formation in a short period].
AB  - A 61-year-old man presented with the complaint of headache. Investigations
      revealed a fusiform middle cerebral artery aneurysm at the M2 part. The formation
      of the aneurysm rapidly developed to a partially thrombosed aneurysm in the
      course of four months. As regards the treatment of the aneurysm, at first we
      tried surgery with a superficial temporal artery middle cerebral artery bypass
      (STA-MCA bypass) and trapping of the aneurysm. However, during the procedure, it
      was difficult to control bleeding from the temporal muscle, bone flap, and
      subdural space. Because of this, we finished the STA-MCA bypass without trapping
      of the aneurysm and then, four days later, we confirmed bypass patency and
      treated the aneurysm using endovascular coil embolization. Based on both surgical
      and interventional investigations in this case and a review of the reported
      literature, the authors propose that there are two mechanisms causing the middle
      cerebral artery fusiform aneurysm to develop thrombosed formation rapidly: (i)
      Peripheral middle cerebral artery branches demand less blood flow than other
      major trunk arteries. (ii) Bypass flow maintains perfusion to the distal
      branches. On the other hand, this flow alteration caused by surgical vascular
      bypass may promote the development of the aneurysm to thrombosed formation. The
      treatment of a fusiform middle cerebral artery aneurysm at the M2 part is also
      discussed.

PMID- 18044230
TI  - [A case of lymphocytic hypophysitis successfully treated with steroid pulse
      therapy].
AB  - Lymphocytic hypophysitis is an autoimmune disorder of the pituitary gland. We
      report a case of lymphocytic hypophysitis managed by high dose methylprednisolone
      pulse therapy and review the literature. A 61-year-old woman presented with
      severe headache. Magnetic resonance imaging (MRI) revealed a contrast enhancing
      pituitary mass. The patient underwent endonasal-transsphenoidal surgery of the
      pituitary lesion under the diagnosis of a non-secreting pituitary adenoma.
      Intraoperative histological findings suggested an inflammatory lesion and we
      performed subtotal resection of the mass. Histopathological examination confirmed
      the diagnosis of lymphocytic hypophysitis. Postoperatively, she received
      methylprednisolone pulse therapy and her severe headache resolved. This case
      report suggests that methylprednisolone pulse therapy may improve the clinical
      symptoms of lymphocytic hypophysitis.

PMID- 18044231
TI  - New Zealand women living with HIV/AIDS: a feminist perspective.
AB  - This paper draws on current and earlier literature, together with observational
      and anecdotal data to reveal the situation of HIV positive women in New Zealand.
      The present picture is examined in relation to data from a previously unpublished
      qualitative study undertaken by the author in 2001 using a feminist perspective.
      It would seem that dominant concerns of the women today are much the same as
      those surfacing in the earlier study. These include stigma and the associated
      problem of whether to conceal or reveal. Additionally these women are concerned
      that health professionals do not always take their problems seriously. Their
      distress is aggravated by fact of them being women suffering from what is
      generally seen as a male disease. The feminist perspective highlights the
      relative powerlessness of many women in the context of sexual relations whereby
      much of the prophylactic advice--such as insistence on condom use--becomes
      irrelevant. New women oriented education programmes are needed. It is argued that
      nurses are well placed to make a positive contribution in this area of care, and
      in fact are obligated to do so if their practice is to be consistent with the
      profession's declared aims with respect to cultural safety. However it is noted
      that there is still a degree of prejudice and ignorance to be overcome before the
      desired results will be achieved.

PMID- 18044232
TI  - New Zealand nurses' reports on hospital care: an international comparison.
AB  - Despite the differences in health care systems, nursing shortages and their
      contributing factors and consequences no longer seem to be solely country
      specific. The present study replicated a cross-national study of nurses'
      perceptions of staffing, work organisation and outcomes conducted in more than
      700 hospitals in the United States, Canada, England, Scotland, and Germany. This
      paper compares the 2001 New Zealand findings with the findings of the five
      country study. New Zealand nurses report similar shortcomings in their work
      environment as do the nurses in countries with distinctly different health care
      systems. While they report similar high levels of competence and good relations
      between doctors and nurses as the respondents in the other five countries, higher
      numbers of New Zealand nurses 30 years of age or younger report their intention
      to leave their current jobs. New Zealand nurses also report the highest levels of
      job related stress, high levels of job dissatisfaction, and more than half report
      receiving inadequate organisational support. The implications of these findings
      are discussed in light of recent changes in the hospital environment.

PMID- 18044233
TI  - Personal autonomy for older people living in residential care: an overview.
AB  - Autonomy has significance for everyone, including those in long-term residential
      care. This article looks at the concept of autonomy particularly in relation to
      the population of older persons living in residential care settings. It examines
      the values underpinning the exercise of personal autonomy and notes how an
      individual's autonomy may be enhanced or restricted. The implications for
      gerontological nursing practice are outlined and suggestions offered as to how
      personal autonomy for older persons living in residential care may be preserved
      and promoted.

PMID- 18044234
TI  - From experience to definition: addressing the question 'what is qualitative
      research?'.
AB  - Most health professionals today have heard of 'qualitative research' but many
      remain confused as to what it is and how to go about doing it. In this paper, two
      experienced qualitative researchers become engaged in conversation exploring the
      question 'what is qualitative research?' Lynne Giddings and Liz Smythe are
      Associate Professors in the Faculty of Health & Environmental Sciences at the
      Auckland University of Technology. They engage a reader in exploring issues such
      as: What might draw you to qualitative research? How does qualitative research
      make a difference to practice? How can reading a qualitative research article
      inform practice? From a qualitative perspective, what is 'truth'? How many
      participants? What happens to the data? What about the bias of the researcher?
      Can qualitative findings be trusted? Stories and exemplars are used to highlight
      the processes and issues involved in undertaking a qualitative research study.

PMID- 18044236
TI  - Making an evidence based decision involves a process of inquiry.

PMID- 18044237
TI  - Health care: for private profit or public good?

PMID- 18044238
TI  - Access to cancer screening for women with long-term mental health problems.

PMID- 18044239
TI  - Working life.

PMID- 18044240
TI  - Effectiveness of interventions for under nourished older inpatients in the
      hospital setting.

PMID- 18044241
TI  - Study asks why alcohol and drug nurses smoke.

PMID- 18044242
TI  - Not "just" a drug and alcohol nurse.

PMID- 18044243
TI  - Reducing harm in the community.

PMID- 18044244
TI  - Supporting people in recovery.

PMID- 18044245
TI  - Building the alcohol and other drug workforce in New Zealand.

PMID- 18044247
TI  - Education and workforce development issues associated with invisibility.

PMID- 18044246
TI  - Pain: the new co-morbidity.

PMID- 18044248
TI  - Inorganic: the other mercury.
AB  - There is a broad array of mercury species to which humans may be exposed. While
      exposure to methylmercury through fish consumption is widely recognized, the
      public is less aware of the sources and potential toxicity of inorganic forms of
      mercury. Some oral and laboratory thermometers, barometers, small batteries,
      thermostats, gas pressure regulators, light switches, dental amalgam fillings,
      cosmetic products, medications, cultural/religious practices, and gold mining all
      represent potential sources of exposure to inorganic forms of mercury. The route
      of exposure, the extent of absorption, the pharmacokinetics, and the effects all
      vary with the specific form of mercury and the magnitude and duration of
      exposure. If exposure is suspected, a number of tissue analyses can be conducted
      to confirm exposure or to determine whether an exposure might reasonably be
      expected to be biologically significant. By contrast with determination of
      exposure to methylmercury, for which hair and blood are credible indicators,
      urine is the preferred biological medium for the determination of exposure to
      inorganic mercury, including elemental mercury, with blood normally being of
      value only if exposure is ongoing. Although treatments are available to help rid
      the body of mercury in cases of extreme exposure, prevention of exposure will
      make such treatments unnecessary. Knowing the sources of mercury and avoiding
      unnecessary exposure are the prudent ways of preventing mercury intoxication.
      When exposure occurs, it should be kept in mind that not all unwanted exposures
      will result in adverse health consequences. In all cases, elimination of the
      source of exposure should be the first priority of public health officials.

PMID- 18044250
TI  - A baseline assessment of U.S. Naval food facilities using the Food Code's new
      risk-based inspection program.
AB  - The Food and Drug Administration (FDA) has developed a new method for assessing
      food safety in retail establishments using a risk factor-based approach for
      prevention of foodborne illness. The study reported here surveyed facilities in
      the Navy's San Diego jurisdiction (11 fast-food and 22 full-service facilities)
      to establish a baseline rate of compliance with FDA risk factor categories. The
      Navy facility baseline-data compliance rate was compared with FDA baseline data
      from 1998. Fast-food facilities were less in compliance than they were in the FDA
      baseline data (59 percent versus 74 percent were in compliance), while full
      service establishments were more in compliance than they were in the FDA baseline
      (73 percent versus 60 percent). The fact that compliance was greater among Navy
      facility full-service establishments than in the FDA national baseline may be
      partly due to staffing by military active-duty employees who receive incentives
      that may encourage compliance. The establishment of this Navy baseline allows
      comparison with the FDA baseline. Interventions can now be quantified.

PMID- 18044249
TI  - Acute hazardous substance releases resulting in adverse health consequences in
      children: Hazardous Substances Emergency Events Surveillance system, 1996-2003.
AB  - Because of their small size and ongoing organ development, children may be more
      susceptible than adults to the harmful effects of toxic chemicals. The objective
      of the study reported here was to identify frequent locations, released
      substances, and factors contributing to short-term chemical exposures associated
      with adverse health consequences experienced by children. The study examined the
      Hazardous Substances Emergency Events Surveillance (HSEES) system data from 1996
      2003. Eligible events involved the acute release of a hazardous substance
      associated with at least one child being injured. The study found that injured
      children were predominantly at school, home, or a recreational center when events
      took place. School-related events were associated with the accidental release of
      acids and the release of pepper spray by pranksters. Carbon monoxide poisonings
      occurring in the home, retail stores, entertainment facilities, and hotels were
      responsible for about 10 percent of events involving child victims. Chlorine was
      one of the top chemicals harmful to children, particularly at public swimming
      pools. Although human error contributed to the majority of releases involving
      child victims, equipment failure was responsible for most chlorine and ammonia
      releases. The authors conclude that chemical releases resulting in injury to
      children occur mostly in schools, homes, and recreational areas. Surveillance of
      acute hazardous chemical releases helped identify contributing causes and can
      guide the development of prevention outreach activities. Chemical accidents
      cannot be entirely prevented, but efforts can be taken to provide safer
      environments in which children can live, learn, and play. Wide dissemination of
      safety recommendations and education programs is required to protect children
      from needless environmental dangers.

PMID- 18044251
TI  - The personal and general hygiene practices of food handlers in the delicatessen
      sections of retail outlets in South Africa.
AB  - This paper presents data on personal- and general-hygiene knowledge and practices
      among food handlers in the delicatessens of a major retail group in the Western
      Cape in South Africa. Food handlers were interviewed by means of a structured
      questionnaire. Although the majority of food handlers adhered to basic hygiene
      principles, there is definitely a need for proper and continuous training in
      personal and general hygiene, not only for food handlers, but also for
      management. The study reported here is of importance particularly in view of new
      local regulations governing the application of the hazard analysis and critical
      control point (HACCP) system. Management is responsible for the implementation of
      this system, and where supervision is not adequate, the manager of the outlet
      should intervene to ensure that staff conform to the requirements.

PMID- 18044252
TI  - Mr. Blake's message.

PMID- 18044253
TI  - Environmental data assessment for use in public health surveillance.
AB  - Public health surveillance is the ongoing systematic collection, analysis,
      interpretation, and dissemination of data on health-related events for use in
      public health action to reduce morbidity and mortality and to improve health.
      Total trihalomethanes are an example of a chemical in drinking water that is
      regulated by the U.S. Environmental Protection Agency (U.S. EPA) but is not under
      public health surveillance. The U.S. EPA database that stores this environmental
      information is called the Safe Drinking Water Information System (SDWIS). Its
      purpose is to collect data on noncompliance events in drinking-water utilities in
      each state. For this discussion, the SDWIS data on TTHMs, which are an example of
      environmental data, were assessed for public health surveillance system
      attributes as defined by the Centers for Disease Control and Prevention:
      simplicity, flexibility, data quality, acceptability, sensitivity, predictive
      value positive, representativeness, timeliness, and stability.

PMID- 18044254
TI  - Time to embrace smoke-free trend.

PMID- 18044255
TI  - Revitalization: are we there yet?

PMID- 18044256
TI  - It's not just Montezuma's revenge anymore...

PMID- 18044257
TI  - Preparing for our profession's future.

PMID- 18044258
TI  - Biomarkers of acute kidney injury: can we replace serum creatinine?
AB  - Acute kidney injury (AKI) is frequent in hospitalized critically ill patients and
      mortality associated with AKI is largely unchanged over many decades. The new
      nomenclature, AKI, reflects the entire spectrum of acute renal failure,
      recognizing that an acute decline in kidney function can be secondary to an
      injury that causes functional or structural changes in the kidneys [Mehta et al.
      2007]. An abrupt change in serum creatinine level has been the primary method for
      diagnosing AKI for nearly 60 years despite its well recognized limitations [Addis
      et al. 1947, Barrett and Addis 1947, Fisher and Wilhelmi 1937, Star 1998]. These
      limitations are mainly related to the delayed diagnosis of AKI associated with
      delayed rise in serum creatinine and the lack of specificity and sensitivity
      associated with small changes in serum creatinine. It is believed that these
      limitations associated with diagnosis of AKI have prevented progress by
      interfering with the design of clinical trials for newer therapies. It is now
      widely believed that the availability of accurate and objective early biomarkers
      of AKI will stimulate progress in the development of early interventions in AKI.
      Recognition of this concept has led to a surge in preclinical, translational and
      clinical research for discovery and validation of biomarkers in AKI. In this
      review we will discuss the role of biomarkers in AKI and the promising biomarkers
      on the horizon.

PMID- 18044259
TI  - Failure of ascorbic acid to prevent contrast-media induced nephropathy in
      patients with renal dysfunction.
AB  - AIMS: Contrast-media induced nephropathy (CIN) remains a common complication
      after contrast dye exposure especially in patients with chronic renal impairment
      (CRI). We sought to evaluate the efficacy of the antioxidant ascorbic acid as an
      adjunct to hydration in limiting the incidence of contrast induced nephrotoxicity
      after coronary procedures. MATERIALS AND METHODS: In a randomized, double-blind,
      prospective, single center-study, 143 consecutive patients with CRI (creatinine
      level > 120 micromol/l) referred to coronary angiography/intervention were
      randomly assigned to receive 1 g ascorbic acid or placebo in adjunct to saline
      hydration prior to and after angiography. Creatinine and urea nitrogen levels
      were measured prior to and up to 6 days after exposure to contrast agent.
      RESULTS: The development of CIN occurred totally in 8/143 (5.6%) patients.
      Between the two groups no significant difference was detected (Vitamin C 5/74
      (6.8%) patients; placebo 3/69 (4.3%) patients). After adjusting for the amount of
      contrast dye, drug treatment, cardiovascular risk factors, ejection fraction, or
      sex, again no differences were detected. No patient required dialysis. More
      patients with diabetes had development of CIN (7/85; 8.2%) compared with
      nondiabetic patients (1/58; 1.7%), although not significant (p = 0.14). The
      incidence of CIN was elevated in patients with high amounts (> 140 ml) of
      contrast volume used (6/8). CONCLUSIONS: Our study does not support the
      prophylactic use of ascorbic acid in patients with renal dysfunction exposed to
      contrast dye.

PMID- 18044260
TI  - Combination therapy of pioglitazone with voglibose improves glycemic control
      safely and rapidly in Japanese type 2-diabetic patients on hemodialysis.
AB  - AIMS: Unfortunately, clinicians are diagnosing a growing number of patients on
      hemodialysis (HD) with insulin-resistant, Type 2 diabetes in Japan. While alpha
      glucosidase inhibitors (alpha-GI) such as oral antidiabetic agents are indicated
      for Japanese diabetics on HD, pioglitazone and other PPARgamma agonists are now
      contraindicated. No prospective study has evaluated the use of thiazolidinediones
      in diabetics with end-stage renal disease (ESRD) in combination with alpha-GI. In
      this study we evaluated the efficacy and safety of pioglitazone in Japanese
      diabetics on HD. METHODS: An open-label randomized study was performed on 31 Type
      2 diabetics on HD with unstable glycemic control receiving constant doses of
      voglibose. The patients were randomly assigned to two groups: a combination
      therapy group (pioglitazone group) administered pioglitazone (fixed dose 30 mg)
      plus voglibose, and a monotherapy group (control group) administered voglibose
      alone. The efficacy of the treatments was determined by monitoring glycemic
      control (plasma glucose and HbA1c) and insulin resistance. Insulin resistance was
      assessed using the homeostasis model assessment for insulin resistance (HOMA-R).
      Safety and tolerance were determined by monitoring clinical and laboratory
      parameters. RESULTS: The pioglitazone was effective in reducing plasma glucose
      and HbA1c from the baseline levels from Week 4 onward. It was also effective in
      reducing triglycerides. HOMA-R decreased significantly at 4 weeks in the
      pioglitazone group, and the decrease continued up to the last measurement at Week
      12. Systolic and diastolic blood pressures at 4 weeks were statistically lower in
      the pioglitazone group than in the control group. No serious adverse effects such
      as hypoglycemia, liver impairment or rhabdomyolysis were observed in any of the
      patients. CONCLUSIONS: Pioglitazone was safe and effective as a treatment for
      diabetics on dialysis therapy. The 30 mg daily dose of pioglitazone was
      sufficient for Japanese HD patients, obese and nonobese alike. The combination
      therapy of pioglitazone with voglibose will add to the list of first-line drug
      treatments for glycemic control in uremic Type 2 diabetes.

PMID- 18044261
TI  - A combination of a PPAR-gamma agonist and an angiotensin II receptor blocker
      attenuates proinflammatory signaling and stimulates expression of Smad7 in human
      peritoneal mesothelial cells.
AB  - BACKGROUND: Human peritoneal mesothelial cells (HPMCs) have been shown to
      regulate the inflammatory response and the subsequent peritoneal extracellular
      matrix accumulation (ECM) induced by bio-incompatible peritoneal dialysis
      solutions. Recently, attention has been given to the possible antiinflammatory
      effect exhibited by angiotensin receptor blockers (ARB) or PPAR-gamma agonists in
      several tissues including glomerular. As no data on the potential role of these
      commonly used drugs in reducing peritoneal fibrosis exist, we examined the in
      vitro effects of an ARB (losartan) and a PPAR-gamma agonist (rosiglitazone) on
      inflammatory and profibrotic pathways in cultured HPMCs subjected to high
      glucose. METHODS: HPMCs were incubated for 48 hours with 3 different
      concentrations of glucose: 5 mM (G5), 50 mM (G50) and 100 mM (G100), as well as
      G50 with either losartan (5 or 10 microM) and/or rosiglitazone (1 or 10 microM).
      IL-6, IL-8, VEGF and TGF-beta1 in the supernatants were measured by cytokine
      multiplex assays or ELISA. Smad7, the inhibitor of the TGF/Smad signaling
      pathway, was measured using immunocytochemistry. RESULTS: All the measured
      cytokines increased in proportion to increased concentration of glucose.
      Unexpectedly, this effect was not inhibited, but rather further enhanced, by
      rosiglitazone and losartan separately. However, only the combination of the two
      drugs had an inhibitory effect on TGF- beta1 and IL-6, while the expression of
      inhibitory Smad7 was increased. CONCLUSION: We conclude that high glucose
      exposure stimulates an inflammatory response in HPMCs in a dose-dependent manner.
      Rosiglitazone and losartan appear to have synergetic effects which could decrease
      fibrosis by inhibiting inflammation and regulating the TGF/Smad signaling
      pathway, but further studies are needed to elucidate the complex pathways
      modulated by these drugs.

PMID- 18044262
TI  - Efficacy and safety of intermittent hemodialysis using citrate as anticoagulant:
      a prospective study.
AB  - BACKGROUND: The use of trisodium-citrate for regional anticoagulation of the
      extracorporal circuit during renal replacement therapy (RRT) has received
      increased interest, particularly in critically ill patients with increased risk
      of bleeding. Continuous renal replacement therapies are the most extensively
      investigated and used procedures in this regard. However, when patients recover
      from critical illness, RRT is often switched to intermittent procedures. In this
      prospective study, we investigated the efficacy and safety of citrate
      anticoagulation during intermittent hemodialysis (IHD) performed with a standard
      roller blood pump device. METHODS: We treated 11 critically ill patients with
      acute renal failure. These patients received a total of 31 intermittent IHD
      treatments. The targeted IHD treatment time was 6 h (4.5 l/h treatment dose). For
      anticoagulation, a 4% trisodium-citrate solution was continuously infused into
      the arterial line of the extracorporeal circuit. A calcium-free, lactate-based
      dialysis solution was used in all treatment procedures. Calcium was continuously
      substituted via a separate central line. Electrolyte and acid-base changes as
      well as the cardiovascular hemodynamics were analyzed. RESULTS: All patients
      achieved the targeted filter life time. Filter clotting did not occur.
      Electrolytes and acid base values were well-maintained throughout the study
      period. Particularly metabolic derangements were not observed. All treatments
      were hemodynamically well-tolerated. CONCLUSIONS: Intermittent hemodialysis with
      citrate anticoagulation can be safely applied in critically ill patients at high
      risk of bleeding.

PMID- 18044263
TI  - Endocapillary proliferative glomerulonephritis with crescent formation and
      concurrent tubulointerstitial nephritis complicating retroperitoneal fibrosis
      with a high serum level of IgG4.
AB  - Renal lesions of IgG4-related disease have been reported recently. Most of them
      are tubulointerstitial nephritis, and a definite glomerulonephritis complicating
      IgG4-related disease is very rare. We report here a case of definite
      glomerulonephritis and concurrent tubulointerstitial nephritis complicating
      retroperitoneal fibrosis with a high serum level of IgG4. A 68-year-old Japanese
      woman was referred to our hospital for investigation of anasarca. We diagnosed
      her disease as a nephrotic syndrome and left hydroureteronephrosis due to
      retroperitoneal fibrosis. Her laboratory data revealed a high serum level of
      IgG4, renal injury, hypoproteinemia, hypocomplementemia, a positive finding of
      circulating immunocomplex (CIC), and negative findings ofautologous antibodies
      suggesting systemic lupus erythematosus (SLE) or Sjogren's syndrome (SS). A
      diagnosis of SLE or SS could not be made clinically. Right renal biopsy revealed
      endocapillary proliferative glomerulonephritis with crescent formation and
      concurrent tubulointerstitial nephritis. Infiltration of plasma cells in
      interstitium was more conspicuous than seen with ordinary tubulointerstitial
      nephritis, and in most of them IgG4 was positive. We placed a percutaneous
      nephrostomy catheter in her left kidney, and prescribed prednisolone and
      cyclosporine. The responses to prednisolone and cyclosporine therapies were very
      good. Further studies are needed to clarify the relationship between
      glomerulonephritis and IgG4-related disease. However, when considering renal
      lesions of IgG4-related disease, we think that hypocomplementemia, a positive
      finding of CIC, negative findings of autologous antibodies suggesting SLE or SS,
      conspicuous interstitial infiltration of IgG4-positive plasma cells, and a good
      response to steroid or immunosuppressant therapy are key points.

PMID- 18044264
TI  - Analysis of MPO-ANCA subtypes in a patient with propylthiouracil-induced
      vasculitis with multiple complications.
AB  - BACKGROUND: We report a 16 year-old girl with propylthiouracil (PTU)-induced
      antineutrophil cytoplasmic antibody (ANCA)-positive glomerulonephritis combined
      with Henoch-Schonlein purpura nephritis (HSPN) and antiphospholipid syndrome
      (APS). CASE AND METHODS: The patient had Graves' disease and had been treated
      with PTU for about 6 years. She complained of arthralgia, epigastralgia, purpura
      of the lower extremities, anemia, and abnormal urinalysis. Lupus anticoagulant
      was positive. Additionally, a high level of anti-myeloperoxidase (MPO) antibodies
      (IgG) and a low level of coagulation factor XIII were recognized. She had several
      complications including lung bleeding, lacuna infarctions of the right frontal
      and parietal brain lobes, and deep vein thrombosis of the left lower extremity.
      We studied tissue histology and carried out MPO-ANCA subtype analysis by
      immunofluorescence and flow cytometry and MPO-ANCA epitope analysis. RESULTS:
      Histologically, purpura showed leukocytoclastic vasculitis with perivascular
      depositions of IgA and complement C3. Renal biopsy showed necrotizing
      glomerulonephritis with crescents and mesangial IgA deposits. Notably, IgG, IgM,
      and IgA ANCA were detected in the patient's serum by flow cytometry and
      immunofluorescence. We diagnosed an overlap syndrome of ANCA-positive vasculitis,
      HSPN, and APS. A change in the reactivity of MPO-ANCA from recognition of only
      the Hg epitope in the C-terminal region to recognition of multiple MPO epitopes
      was accompanied by a remission of symptoms. CONCLUSIONS: This report may provide
      a very rare description of an overlap syndrome of PTU-induced ANCA vasculitis,
      HSPN, and APS in which not only IgG ANCA but also IgA and IgM ANCA were found.
      Epitope analysis may be a useful marker for disease-monitoring of PTU-induced
      ANCA-positive vasculitis. This case may provide insight into the pathological
      mechanism underlying each of these diseases.

PMID- 18044265
TI  - Successful therapeutic use of rituximab in refractory Wegener's granulomatosis
      after renal transplantation.
AB  - Wegener's granulomatosis is a significant cause of end-stage renal disease
      requiring renal replacement therapy. Treatment of relapses is often difficult as
      immunosuppressive therapy can be limited by various factors including graft
      survival in renal transplantation. Rituximab is a novel therapeutic approach in
      those conditions. We present the case of a 42 year-old Caucasian woman who had
      been diagnosed with Wegener's granulomatosis 15 years ago. Predominantly affected
      organs were kidneys and pituitary gland. Five years later she reached end-stage
      renal failure and received a renal transplant soon after. She suffered from
      continuous relapses involving pulmonary hemorrhage and treatment became
      increasingly difficult. Symptoms resolved soon after single administration of low
      dose rituximab.

PMID- 18044266
TI  - Linezolid-induced interstitial nephritis in a kidney-transplant patient.
AB  - Linezolid is a recent oral antibiotic used in drug-resistant Gram-positive cocci
      infections. Herein, we report on the first case of linezolid-related acute renal
      failure in a kidney-transplant patient. A 60-year-old male having autosomic
      polycystic kidney disease with liver involvement, on cyclosporin A, mycophenolate
      mofetil and very low dose prednisolone, presented with an Enterococcus faecium
      abscess of a huge liver cyst, which was treated by percutaneous drainage and
      linezolid therapy. Eight days after starting linezolid, he presented with acute
      renal failure, i.e. serum creatinine increased from 136- 221 micromol/l,
      associated with mild hypereosinophilia, anemia and thrombocytopenia. There was no
      skin rash, arthralgia, eosinophiluria or proteinuria. The transplant kidney
      biopsy, performed 15 days after the beginning of linezolid therapy, showed
      interstitial nephritis and focal tubular atrophy. After linezolid withdrawal and
      increasing prednisolone daily dose to 20 mg/d, within a few days, serum
      creatinine had decreased; after 2 and 4 weeks post linezolid withdrawal, his
      serum creatinine was 166 and 159 micromol/l, respectively. Because of the
      potential side effects of linezolid, i.e. myelosuppression and possibly
      nephrotoxicity, we recommend close monitoring of these parameters when linezolid
      therapy is attempted in kidney transplant patients.

PMID- 18044267
TI  - Proteinuria disappears promptly after simultaneous kidney-pancreas
      transplantation in nephrotic diabetic patients with near-normal GFR.
AB  - Preemptive simultaneous kidney-pancreas transplantation (SKPT) was performed in
      two patients with Type 1 diabetes and nephrotic syndrome due to diabetic
      nephropathy, although the native kidneys exhibited near-normal function. Before
      and 3 months as well as 12 months after SKPT S-creatinine, creatinine clearance
      (Cr-Cl) and urinary protein excretion were measured. Additionally, 99mTC
      scintigraphic examinations of the kidneys were performed 3 and 12 months after
      SKPT. Thereby, the injected 99mTC activities were assessed in the kidney graft as
      well as in the patient's native kidneys. Aim of the study was to find out the
      impact of successful SKPT on proteinuria and further functioning of the patient's
      own kidneys after transplantation. Indication for pancreas transplantation was
      severe diabetic autonomic neuropathy and Brittle diabetes, respectively. In
      Patient 1, we registered 3 months after SKPT a near-normal protein excretion of
      mean 0.20 g/24-h urine at a Cr-Cl of 82 ml/ min. The scintigraphic examinations
      showed 60% of the radioactivity in the kidney graft and 40% in the patient's own
      kidneys (22% right and 18% left). Data 1 year after SKPT were: mean protein
      excretion 0.28 g/24-h urine, Cr-Cl 78 ml/min and in the scan, furthermore, 30% of
      the activity in the patient's native kidneys (16% right and 14% left). In Patient
      2 after 3 months we obtained a mean protein excretion of 0.18 g/24-h urine at a
      Cr-Cl of 80 ml/min. Scintigram of the kidneys: 58% of the injected activity were
      measured in the kidney graft and 42% in the patient's own kidneys (22% right and
      20% left). After 12 months of SKPT we measured a mean protein of 0.26 g/24-h
      urine and Cr-Cl 78 ml/min. Scintigram of the kidneys: 36% of the activity was in
      the patient's native kidneys (18% right and left). We conclude that in diabetic
      patients with nephrotic syndrome and near-normal function of the native kidneys
      SKPT leads to rapid and nearly complete diminution of proteinuria although the
      residual function of the patient's native kidneys was about 40% at 3 months after
      transplantation and slightly lower at 12 months after SKPT.

PMID- 18044268
TI  - Prognosis of mesangial glomerulonephritis in patients with rheumatoid arthritis.

PMID- 18044269
TI  - Minimal change variants with mesangial IgA deposits.

PMID- 18044270
TI  - Gross hematuria as a manifestation of membranous nephropathy.

PMID- 18044271
TI  - Optimism, stress, life satisfaction, and job burnout in restaurant managers.
AB  - Researchers have suggested that dispositional optimism is related to both stress
      and stress outcomes. However, the nature of this relationship has not fully been
      explained. The authors contributed to a better understanding of this relationship
      by evaluating dispositional optimism, stress, overall life satisfaction, and job
      burnout in a sample of restaurant managers. Results indicated that stress and job
      burnout were significantly related; however, their relationship was not moderated
      by dispositional optimism, as would be suggested by the results of past research.
      The diminished personal accomplishment dimension of job burnout mediated the
      relationship between optimism and life satisfaction. Also, stress significantly
      impacted perceptions of diminished personal accomplishment and life satisfaction.

PMID- 18044272
TI  - Values most extolled in Nobel Peace Prize speeches.
AB  - The authors randomly selected 50 Nobel Peace Prize speeches and content analyzed
      them to determine which values the speakers extolled most frequently. The 10 most
      frequently mentioned values were peace (in 100% of the speeches), hope (92%),
      security (86%), justice (85%), responsibility (81%), liberty (80%), tolerance
      (79%), altruism (75%), God (49%), and truth (38%). The authors discuss the
      interplay of these values in the modern world and implications regarding the
      search for universal moral values.

PMID- 18044273
TI  - The dynamic change of self-efficacy in information searching on the Internet:
      influence of valence of experience and prior self-efficacy.
AB  - The authors investigated the dynamic change of specific self-efficacy in
      information searching on the Internet. In Study 1, the valence of experience was
      manipulated by task difficulty to obtain the developmental curve of self-efficacy
      change in consecutive information-searching trials. The results indicated that
      positive task experiences in information searching elicited a linear increase in
      self-efficacy. In contrast, negative task experiences elicited a more rapid
      decrease in self-efficacy. Self-efficacy of participants decreased to a lower
      level after the first negative experience and displayed a quadratic trend toward
      a floor effect. In Study 2, the authors examined the moderating effect of initial
      self-efficacy on the valence of experience. The enhancement effect of positive
      task experience on self-efficacy was more pronounced for individuals with lower
      levels of self-efficacy, whereas the deteriorating effect of negative experience
      was more prominent for individuals with higher levels of self-efficacy.

PMID- 18044274
TI  - Cognitive motivation correlates of coping style in decisional conflict.
AB  - Can personality traits account for the handling of internal conflicts? The
      authors explored how individual differences in information-processing style
      affect coping patterns displayed before making important decisions. Need for
      cognition and need for cognitive closure were linked to the major tendencies
      identified in the conflict theory of decision making: vigilance, hypervigilance,
      and defensive avoidance (buck passing and procrastination). A sample of 1,119
      Belgian human resource professionals completed the Melbourne Decision Making
      Questionnaire, the 18-item short-form Need for Cognition Scale, and the Need for
      Closure Inventory. Ordinary least squares regression analysis indicated that
      significant relationships existed between need for cognition, need for closure,
      and conflict decision-making styles. The authors also found significant effects
      of gender and age.

PMID- 18044275
TI  - Predicting the decision to pursue mediation in civil disputes: a hierarchical
      classes analysis.
AB  - Clients (N = 185) involved in civil court cases completed the CPR Institute's
      Mediation Screen, which is designed to assist in making a decision about pursuing
      mediation. The authors modeled data using hierarchical classes analysis (HICLAS),
      a clustering algorithm that places clients into 1 set of classes and CPRMS items
      into another set of classes. HICLAS then links the sets of classes so that any
      class of clients can be identified in terms of the classes of items they
      endorsed. HICLAS-derived item classes reflected 2 underlying themes: (a)
      suitability of the dispute for a problem-solving process and (b) potential
      benefits of mediation. All clients who perceived that mediation would be
      beneficial also believed that the context of their conflict was favorable to
      mediation; however, not all clients who saw a favorable context believed they
      would benefit from mediation. The majority of clients who agreed to pursue
      mediation endorsed items reflecting both contextual suitability and perceived
      benefits of mediation.

PMID- 18044276
TI  - Perceptions of ambiguously unpleasant interracial interactions: a structural
      equation modeling approach.
AB  - Despite a general consensus in the United States that overtly racist acts are
      unacceptable, many ambiguous situations in everyday life raise questions of
      whether racism has influenced a person's behavior in an interracial encounter.
      The authors of the present study sought to (a) examine simultaneously an array of
      variables thought to be related to perceived racism and (b) investigate how the
      contribution of these variables may differ with respect to the asymmetry
      hypothesis, which suggests that acts of discrimination from a dominant person
      toward a subordinate person will be viewed as more biased than if the situation
      were reversed. The authors used a dual structural equation modeling approach.
      Results indicated that ethnic identity significantly predicted perceived racism.
      In addition, the extent to which cognitive interpretation style significantly
      predicted perceived racism depended on the ethnicity of participants involved in
      the interaction.

PMID- 18044277
TI  - Cecil Gray the man who revolutionized anesthesia practice.

PMID- 18044278
TI  - The accuracy of non-invasive nasal capnography in morbidly obese patients after
      bariatric surgery.
AB  - STUDY OBJECTIVE: to assess the accuracy of nasal capnography for the monitoring
      of ventilation in extubated morbidly obese patients, following bariatric surgery.
      DESIGN: prospective descriptive study. SETTING: Post-anesthesia care unit.
      PATIENTS: 25 consecutive morbidly obese patients admitted to the PACU after open
      bariatric surgery. INTERVENTION: Patients had a nasal cannula designed to
      administer oxygen (3 L/min) and to sample expired CO2 by a coaxial catheter.
      MEASUREMENTS: Capnographic waveform, end-tidal CO2 (ETCO2) and respiratory rate
      (RRd) were displayed by a capnometer (Datex-Ohmeda). Arterial CO2 pressure
      (PaCO2) was measured by blood gas analysis. Respiratory rate was measured by
      visual inspection of chest breathing motions (RRm). Differences between PaCO2 and
      ETCO2 and between RRd and RRm were calculated for every simultaneous set of
      measurements. RESULTS: Bias, precision, limits of agreement (bias +/- 2
      precisions) between PetCO2 and PaCO2 were respectively as follows: 3.1, 1.4, 0.3
      to 5.9 mmHg with a Pearson correlation coefficient of 0.6 and a P value of 0.001.
      As for RRd v/s RRm the values were: 2, 0.5, 1 to 3 breaths per minute and 0.8
      with the same P value for the Pearson coefficient. CONCLUSION: Limits of
      agreement between PaCO2 and ETCO2 pressure and between RRd and RRm are clinically
      acceptable. Nasal capnography is accurate for the monitoring of ventilation in
      extubated morbidly obese patients, following bariatric surgery.

PMID- 18044279
TI  - Management of the patient reporting an allergy to penicillin.
AB  - Recent emphasis on the prevention of surgical wound infection has highlighted the
      role of the anesthesiologist as the physician responsible for administering
      appropriate antibiotic prophylaxis. Patients often report a distant or unclear
      history of penicillin allergy. Administering an antibiotic to which the patient
      has a true allergy can provoke a life threatening reaction. The anesthesiologist
      should be aware of the prevalence, severity, and manifestations of allergies to
      antibiotics, as well as the available alternatives. Unnecessary administration of
      more powerful broad-spectrum antibiotics leads to the development of
      antimicrobial resistance and should be avoided. It is the anesthesiologists' duty
      to balance these issues when selecting appropriate antibiosis.

PMID- 18044280
TI  - Early graft function and carboxyhemoglobin level in liver transplanted patients.
AB  - INTRODUCTION: Heme-Oxygenase-1 catalyzes hemoglobin into bilirubin, iron, and
      carbon monoxide, a well known vasodilator. Heme-Oxygenase-1 expression and carbon
      monoxide production as measured by blood carboxyhemoglobin levels, increase in
      end stage liver disease patients. We hypothesized that there may be a correlation
      between carboxyhemoglobin level and early graft function in patients undergoing
      liver transplant surgeries. METHODS: In a descriptive retrospective study, 39
      patients who underwent liver transplantation between the year 2005 and 2006 at
      KFSH&RC, are included in the study. All patients received general anesthesia with
      isoflurane in 50% oxygen and air. Levels of oxyhemoglobin, carboxyhemoglobin and
      methemoglobin concentration in percentage were recorded at preoperative time,
      anhepatic phase, end of surgery, ICU admission and 24 hr after surgery. The level
      of lactic acid, prothrombin time (PT), partial thrombin time (PTT), serum total
      bilirubin and ammonia were also recorded at ICU admission and 24 hr after
      surgery. The numbers of blood units transfused were recorded. RESULTS: 39
      patients were included in the study with 13/39 for living donor liver transplant
      (LDLT) compared to 26/39 patients scheduled for deceased donor liver transplant
      (DDLT). The mean age was 35.9 +/- 16.9 years while the mean body weight was 60.3
      +/- 20.9 Kg. Female to male ratio was 21/18. The median packed red blood cell
      (PRBC) units was 4 (Rang 0-40). There was a significant increase in
      carboxyhemoglobin level during the anhepatic phase, end of surgery and on ICU
      admission compared with preoperative value (p<0.005). However, there was
      insignificant changes in methemoglobin level and significant decrease in
      oxyhemoglobin levels throughout the study period compared to the preoperative
      value (p<0.005). The changes in carboxyhemoglobin level on ICU admission and 24
      hrs postoperatively were positively correlated with the changes in serum total
      bilirubin and prothrombin time (R = 0.35, 0.382, 0.325 and 0.31) respectively
      p<0.05) but not with the changes in serum lactic acid. The same strong
      correlation was found when analysing LDLT and DDLT patients separately between
      carboxyhemoglobin concentration and PT and total bilirubin while still the
      correlation with lactic acid was weak. There was no correlation between average
      perioperative carboxyhemoglobin concentration during different timing of
      measurements and average units of transfused blood (R = -0.02) p>0.05.
      CONCLUSION: The changes in carboxyhemoglobin level significantly correlate with
      the Changes in graft functions particularly prothrombin time and serum total
      bilirubin and may be used as an early, rapid and simple test for early evaluation
      of graft function.

PMID- 18044281
TI  - Progressive hypoxemia, hypercarbia and hyperthermia associated with prolonged
      anesthesia--a case report.
AB  - The authors report a case of 66-year-old female patient, 55 kg, ASA I who, under
      general anesthesia in supine position, developed gradual hypoxemia (from a
      baseline PaO2 of 250 to 91 mmHg), carbon dioxide build up (from a baseline PaCO2
      31 to 41 mmHg) associated with gradual hyperthermia up to 38.3 degrees C over
      seven hours, intraoperatively. These observations were noted while using a semi
      closed carbon dioxide absorption circuit in conjunction with the Hygroster filter
      at a fresh gas flow of 4 1/min of 50% nitrous oxide in oxygen. While the
      ventilation pattern was unchanged throughout the procedure, there was a change in
      exhaled tidal and minute ventilation volume with a net decrease of 28 ml and 0.4
      l/min respectively. Findings are probably the result of pulmonary atelecatasis
      under general anesthesia due to the use of a relatively high-inspired oxygen
      concentration (50%). In addition, the use of a high humidity and temperature heat
      moisture exchanger (HME) filter (Hygroster) in conjunction with the circle
      absorber system may have resulted in over humidification and aggravated the
      pulmonary atelecatasis over the long operative time.

PMID- 18044282
TI  - Effects of dexmedetomidine in morbidly obese patients undergoing laparoscopic
      gastric bypass.
AB  - BACKGROUND: Obese patients may be sensitive to the respiratory depressant effect
      of opioid analgesics. Alternative methods for analgesia may be beneficial for
      management of bariatric surgery. We evaluated the effect of dexmedetomidine on
      anesthetic requirements during surgery, hemodynamic, recovery profile and
      morphine use in the postoperative period. METHODS: Eighty adult patients
      scheduled for elective laparoscopic Roux-en-Y gastric bypass surgery were
      randomly assigned to one of two study groups; Group D (40 patients) received
      dexmedetomidine (0.8-microg/kg bolus, 0,4 microg kg(-1) h) and Group P (40
      patients) received normal saline (placebo) in the same volume and rate.
      Intraoperative and postoperative mean blood pressure and heart rate were
      recorded. The total amount of intraoperative fentanyl and propofol required to
      maintain anesthesia were measured. Recovery profile, pain score and total amount
      of morphine used via patient controlled analgesia (PCA) were assessed. RESULTS:
      During surgery, dexmedetomidine decreased the total amount of intraoperative
      fentanyl and propofol required for maintenance of anesthesia compared to placebo.
      Patients who received dexmedetomidine showed significant decrease of
      intraoperative and postoperative mean blood pressure, heart rate. In the
      postoperative period, dexmedetomidine decreased pain scores and PCA morphine use
      significantly and showed better recovery profile as compared to the placebo
      Group. There was no difference in the incidence of postoperative nausea and
      vomiting (PONV) between both groups. CONCLUSION: The intraoperative infusion of
      dexmedetomidine decreased the total amount of propofol and fentanyl required to
      maintain anesthesia, offered better control of intraoperative and postoperative
      hemodynamics, decreased postoperative pain level, decreased the total amount of
      morphine used and showed better recovery profile compared with placebo.

PMID- 18044283
TI  - Anesthesia for laparoscopic cholecystectomy: comparative evaluation-
      desflurane/sevoflurane vs. propofol.
AB  - Laparoscopic techniques, have rapidly increased in popularity because of its
      various benefits. They are widely used in day-case surgical operations and are
      extensively published. However, postoperative nausea vomiting (PONV) is a
      commonly observed phenomenon after laparoscopic procedures. Its occurrence may
      increase depending on the anesthetic techniques used. Despite the fact that the
      use of propofol and the new low solubility inhalation anesthetics, lead to faster
      induction and recovery, their effects on PONV is not sufficiently known.
      Therefore, the aim of this study is to compare the effects of various anesthetic
      drugs on recovery characteristics and PONV. Following informed consent, 300 ASA I
      III patients scheduled for laparoscopic cholecystectomy were investigated.
      Anesthesia was induced by 1.5 microgkg(-1) fentanyl, 0.03 mgkg(-1) midazolam, 1.5
      mgkg(-1) propofol and 0.01 mgkg(-1) vecuronium for all patients. Anesthesia was
      maintained with desflurane in group D (n = 100), sevoflurane in group S (n = 100)
      and propofol infusion in group P (n = 100), beside 50% N20/O2 ventilation. All
      patients were given 4 mg ondansetron and 8 mg dexamethazone iv for preventing
      PONV, ten minutes before the end of surgery. At the end of the operation, times
      for extubation, eye opening, orientation, sitting and walking, and the need of
      ondansetrone in post anesthetic care unit, were recorded. Also, PONV was observed
      and recorded as early period (first 4 hours) and late period (4-24 hours).
      Extubation and eye opening times were meaningfully lower in group D. However, no
      significant differences were observed in orientation, sitting and walking times
      and PONV among the three groups. All patients who had PONV were women. A
      correlation was found between PONV and body weight. Even though there were no
      statistically significant differences among the groups regarding PONV, the number
      of patients who had PONV in group P was lower. Early recovery time was shortest
      in group D, while delayed recovery time had no differences. It may be said that
      these anesthetic drugs have no statistically significant difference for PONV and
      delayed recovery.

PMID- 18044284
TI  - Cisatracurium in cardiac surgery--continuous infusion vs. bolus administration.
AB  - The aim of this study was the comparison of infusion vs. intermittent bolus
      administration of cisatracurium (CA) following cardiac surgery with regard to
      total intraoperative dose and time of recovery from neuromuscular blockade. From
      June 2005 to April 2006 sixty ASA II-III patients who were undergoing coronary
      bypass graft and valve replacement surgery, were equally divided and randomized
      to receive either intermittent bolus (Group A, n = 30) or continuous infusion
      (Group B, n = 30) of CA in Madani Heart Center in the Tabriz (Iran). Total
      intraoperative dose of CA and time to TOF ratio = 0.8 after operation were
      measured. Anesthesia technique in two groups was the same. All of the patients
      underwent cardiopulmonary bypass. Intensity of neuromuscular blockade maintained
      on one train-of-four (TOF) twitch response of adductor pollicis during operation.
      Mean received dose of CA was 32.8 +/- 20.6 micro/kg/hr in Group A and 89.7 +/-
      39.4 micro/kg/hr in Group B (p = 0.003). Total intraoperative dose of CA was 23.6
      +/- 4.9 mg in Group A and 39.2 +/- 10.1 mg in Group B (p = 0.001). Spontaneous
      recovery from neuromuscular blockade in ICU (TOF ratio = 0.8) was reached in 43.8
      +/- 9.2 min in Group A, and 64.2 +/- 15.1 min in Group B (p = 0.0001). Intubation
      time in ICU was not significantly different (Group A = 8.3 +/- 5.1 hrs vs. Group
      B = 10.2 +/- 6.2 hrs, p = 0.256). These results support the intermittent bolus
      administration of cisatracurium in cardiac surgery following cardiopulmonary
      bypass.

PMID- 18044285
TI  - The impact of music on postoperative pain and anxiety following cesarean section.
AB  - BACKGROUND: The relief of post-cesarean delivery pain is important. Good pain
      relief improves mobility and reduces the risk of thromboembolic disease, which
      may have been increased during pregnancy. Pain may impair the mother's ability to
      optimally care for her infant in the immediate postpartum period and may
      adversely affect early interactions between mother and infant. It is necessary,
      therefore that pain relief be safe and effective and results in no adverse
      neonatal effects during breast-feeding. Music may be considered as a potential
      method of post cesarean pain therapy due to its noninvasiveness and lack of side
      effects. In this study we evaluated the effect of intraoperative music under
      general anesthesia for reducing the postoperative morphine requirements after
      cesarean section. METHODS: In a double blind placebo-controlled trial, 100 women
      (ASA I) scheduled for elective cesarean section under general anesthesia, were
      randomly allocated into two groups of fifty. After standardization of anesthesia,
      patients in the music group were exposed to a compact disk of Spanish guitar
      after induction of anesthesia up to the time of wound dressing. In the control
      group patients were exposed to white music. Post operative pain and anxiety were
      evaluated by visual analog scale (VAS) up to six hours after discharge from PACU.
      Morphine was given intravenously for reducing pain to VAS < or = 3
      postoperatively. RESULTS: There was not statistically significant difference in
      VAS for pain between two groups up to six hours postoperatively (P>0.05). In
      addition, morphine requirements were not different between two groups at
      different time intervals up to six hours postoperatively (P>0.05). There were not
      statistically significant difference between two groups regarding postoperative
      anxiety score and vomiting frequency (P>0.05). CONCLUSION: As per conditions of
      this study, intraoperative Spanish music was not effective in reducing
      postoperative pain after cesarean section. In addition postoperative morphine
      requirement, anxiety, and vomiting were not affected by the music during general
      anesthesia.

PMID- 18044286
TI  - Intraoperative awareness--a three year prospective study using bispectral index
      monitor (BIS).
AB  - Patients who experience awareness under surgery may suffer from the post
      traumatic stress disorder (PTSD) with its long-lasting psychological damage. In
      addition, there are also media attention and legal consequences. In spite of
      understanding its causes, it is still occurring worldwide. This prospective study
      was conducted to determine the incidence of awareness using the bispectral index
      monitor (BIS) when its causes are eliminated. There were 2328 patients admitted
      to the study. Their ages ranged from 14-104 yr (mean 38.6 yr). All patients were
      interviewed in the postoperative period. There was no report of awareness during
      the course of surgery. Pre-and intraoperative anesthetic attention to patients
      presented for surgery, together with the use of modern anesthetic delivery units
      possessing facilities for monitoring BIS, and anesthetic gases, and the provision
      of good analgesia, are the most important combination in eliminating awareness
      during surgery.

PMID- 18044287
TI  - Analgesia for retrobulbar block--comparison of remifentanil, alfentanil and
      fentanyl.
AB  - BACKGROUND: The injection of retrobulbar block is associated with significant
      pain and discomfort. Therefore a short-acting IV analgesic before retrobulbar
      injection has been advocated. OBJECTIVE: To compare remifentanil, alfentanil and
      fentanyl in providing analgesia for retrobulbar block injection. METHODS: 69
      patients were enrolled randomly into three groups of 23 each to receive either
      Remifentanil 1 microg/kg, Alfentanil 20 microg/kg or Fentanyl 2 microg/kg as an
      IV bolus dose prior to retrobulbar injection. Mean arterial pressure (MAP) and
      heart rate (HR) were recorded and Numerical Pain Score (NPS) were assessed by a
      blinded observer. RESULTS: Remifentanil prevented increase in MAP and HR while
      alfentanil and fentanyl were ineffective in this purpose (p < 0.05). NPS was
      significantly lower in remifentanil group (p < 0.05). CONCLUSION: Remifentanil 1
      microg/kg prior to retrobulbar injection provide excellent hemodynamic stability
      and ensure analgesia.

PMID- 18044288
TI  - Hemodynamic variation following induction and tracheal intubation--thiopental vs
      propofol.
AB  - BACKGROUND/AIM: Hemodynamic variations are inevitable during induction of
      anesthetic drugs. The present study, investigates the hemodynamic variations of
      two different drugs used for induction; Thiopental vs. Propofol. MATERIALS AND
      METHODS: In a prospective randomized double-blind study, from June 2003 to
      November 2004, 120 (ASA I and II) patients scheduled for elective surgery, were
      randomly divided into two equal groups. Patients were premedicated with midazolam
      (0.05 mg/kg) and fentanyl (1 microg/kg). Anesthesia was induced with either
      thiopental 5 mg/kg (group T) or propofol 2 mg/kg (group P). Neuromuscular
      blockade was achieved with atracurium (0.5 mg/kg) and anesthesia was maintained
      with halothane 1%, nitrous oxide (67%) in O2. Hemodynamic variable (systolic and
      diastolic blood pressure, mean arterial pressure and heart rate) were measured
      non-invasively in three periods: before drug administration, immediately after
      injection, prior to intubation, and finally immediately after intubation.
      RESULTS: the incidence of hemodynamic changes in systolic, diastolic, mean
      arterial blood pressures and heart rate were significantly higher in group T
      compared to group P. CONCLUSION: We conclude that Propofol causes less
      hemodynamic changes compared to Thiopental. Therefore, we recommend Propofol
      especially when dealing with hemodynamically compromised patients.

PMID- 18044289
TI  - Laryngeal mask insertion--effect of age on hemodynamic responses.

PMID- 18044290
TI  - Reverse LMA insertion in a neonate with Klippel-Feil syndrome--case report.

PMID- 18044291
TI  - Painless injection of propofol: pretreatment with ketamine vs thiopental,
      meperidine, and lidocaine.
AB  - Propofol, a commonly used anesthetic, often causes pain on injection. Several
      methods have been described to reduce this pain, however, complete inhibition has
      not been achieved. Our randomized, placebo controlled, double blind study has
      been conducted to compare the analgesic efficacy of iv pretreatment of ketamine,
      meperidine, thiopental, lidocaine to minimize the injection pain of propofol. 125
      patients ASA I and II were randomly allocated into 5 groups and received. Group
      K, ketamine 0.4 mg/kg; Group T, thiopental 0.5 mg/kg; Group M, meperidine 0.5
      [corrected] mg/kg; Group L, lidocaine 1 mg/kg; Group S, saline 3 ml. All
      pretreatment drugs were made into 4 ml solutions and were accompanied by manual
      venous occlusion for 1 min, followed by tourniquet release and slowly IV
      administration of propofol. Pain was assessed with a four point scale. All
      treatment groups had a significantly lower incidence of pain than placebo group
      (p <0.05). However, it has been observed that pretreatment with ketamine was the
      most effective in attenuating pain associated with propofol injection (p <0.05).
      For painless injection of propofol, routine pretreatment with ketamine 0.4 mg/kg
      along with venous occlusion is recommended.

PMID- 18044292
TI  - Admission hypomagnesemia--impact on mortality or morbidity in critically ill
      patients.
AB  - BACKGROUND/OBJECTIVE: No previous study exists to evaluate admission serum
      magnesium level as a predictor of morbidity or mortality. The aim of this study
      was to define the prevalence of admission hypomagnesemia in critically ill
      patients and to evaluate its relationship with organ dysfunction, length of stay,
      and mortality. METHODS: A retrospective study was done on 100 patients > or =16
      years old, admitted to the medical-surgical intensive care unit (ICU) at the
      University Hospital over 2 years period. Observations were made on admission
      total serum magnesium level, a variety of lab tests related to magnesium, need
      for ventilator, duration of mechanical ventilation, hospital/ICU lengths of stay,
      and general patient demographics. RESULTS: The serum magnesium level (normal
      value, 1.3-2.1 mEq/L) was measured at admission. At admission, 51% of patients
      had hypomagnesemia, 49% had normal magnesium levels. There was significant
      difference in mortality rate (55% vs 35%), the length of hospital (15.29 +/- 0.66
      vs 12.81 +/- 0.91), or ICU (9.16 +/- 0.53 vs 5.71 +/- 0.55) stay between these
      two groups of patients (p < 0.05 for all). Hypomagnesemic patients more
      frequently had total hypocalcemia, hypokalemia, and hyponatremia. A total of 51
      patients developed hypomagnesemia during their ICU stay; these patients had
      higher Acute Physiology And Chronic Health Evaluation II (APACHE II) (14.16 +/-
      1.03 vs 10.80 +/- 0.94) and Sequential Organ Failure Assessment (SOFA; 10.89 +/-
      0.90 vs 7.58 +/- 5.01) scores at admission (p < 0.01 for both), a higher maximum
      SOFA score during their ICU stay (14.75 +/- 0.73 vs 8.08 +/- 0.52, p < 0.01), a
      more need to ventilator (58.6% vs 41.4%, p < 0.05), and longer duration of
      mechanical ventilation (7.2 vs 4.7 day, p < 0.01) than the other patients. The
      ROC curve of SOFA score in the hypomagnesemia yields significantly better results
      than APACHE II. An increase of 5 units in the APACHE II or SOFA measured on
      admission increase relative probability of hypomagnesemia by a factor of 0.12 and
      0.16 respectively. CONCLUSION: Development of hypomagnesemia during an ICU stay
      is associated with guarded prognosis. Monitoring of serum magnesium levels may
      have prognostic, and perhaps therapeutic, implications.

PMID- 18044293
TI  - Relationship between serum magnesium level and arrythmias following post-coronary
      artery bypass grafting.
AB  - INTRODUCTION: Atrial and ventricular arrhythmias are among the most common
      complications after coronary artery bypass graft (CABG) surgery. It is known that
      cardiopulmonary bypass reduces serum magnesium level. In this study, we evaluated
      the relationship between total blood magnesium level (TMG) and the incidence of
      perioperative arrhythmias. METHODS: TMG was measured in patients who were
      scheduled for CABG on three occasions: just before anesthesia, on intensive care
      unit (ICU) arrival and on the first morning after operation. Patients were
      evaluated for primary cardiac rhythm, serum creatinine, urine output in operating
      room and diuretic therapy. Supplemental magnesium (SMG) was also recorded in
      operating room and ICU. Patients were then evaluated for the rate and kind of
      arrhythmia occurring during the next 3 days. RESULTS: Mean TMG level in 170 cases
      was 2.2 (0.5), 2.6 (0.6) and 2.4 (0.6) mg/dl on three occasions respectively. 53
      patients developed post-operative arrhythmia (31%) [Atrial Fibrillation (AF)
      (7.1%), Non-AF Supraventricular arrhythmia (14.7%) and Ventricular arrhythmia
      (16.5%)]. Although there was a significant difference between TMG on three
      occasions (P <0.001), all values were within normal range. Although TMG was
      higher in arrhythmic patients compared to non- arrhythmics (2.26 vs. 2.14), both
      values were in normal range and there was no significant difference between two
      groups. DISCUSSION: This study shows that routine magnesium administration has no
      significant effect on serum magnesium level. We conclude that though routine
      regimen of magnesium administration has no effect on incidence of perioperative
      arrhythmia, it is probably necessary for maintaining normal magnesium level.

PMID- 18044294
TI  - Prolonged muscle weakness following general anesthesia in a parturient on
      combined antiretroviral therapy--a case report.
AB  - We report a case of an otherwise healthy; ambulatory 32 year old parturient on
      combined antiretroviral therapy that developed prolonged muscle weakness needing
      postoperative artificial ventilation. Despite no preoperative indication of
      muscle weakness, she developed respiratory insufficiency following general
      anesthesia with drugs that are deemed safe for her condition. After ruling out
      all the likely causes for her respiratory insufficiency that needed 12 hrs of
      artificial ventilation, we address the issue of undiagnosed preoperative muscle
      weakness as a likely cause for her problem. The role of a preoperative
      neurological evaluation to caution the anesthesiologist of the likelihood of a
      possible need for prolonged artificial ventilation following general anesthesia
      in this subgroup of patients, emphasized.

PMID- 18044295
TI  - Pheumocephalus in an infant with Ohtahara syndrome--a case report.

PMID- 18044296
TI  - Intervertebral disc a source of pain? Low back pain: problems and future
      directions--case reports.
AB  - OBJECTIVE: The objective of this article is to provide evidence supporting the
      idea that intervertebral disc is a source of low back pain. SUMMARY OF BACKGROUND
      DATA: Diagnostic tests currently available for diagnosis of a painful disc are
      inadequate. Treatment protocols for low back pain generally ignore the presence
      of a painful disc. Pathological processes that may be responsible for discogenic
      pain are incompletely understood. Without diagnosis and treatment, disc
      disruption evolves to advanced stages of spinal dysfunction. New treatment
      modalities are becoming available which if applied early may stop disc
      disruption. CASE REPORTS: We describe here two case reports where discogenic
      nature of patients' symptoms was suspected based on patients' history, MRI
      findings and discography. We highlight the inadequacies of spinal imaging and
      discography in detecting at painful disc. A treatment (Intradiscal electrothermal
      therapy) was then directed exclusively to the intervertebral discs. We provide
      arguments that link discal therapy to resolution of patients' symptoms.
      Resolution of patients' symptoms after the discal treatment raised our suspicion
      that pain emanated from the intervertebral discs. CONCLUSIONS: Intervertebral
      disc is a source of low back pain that is often ignored. No diagnostic test
      currently exists that can reliably confirm presence of a painful disc. Early
      diagnosis and treatment of a painful disc may reduce enormous pain and suffering
      from low back pain.

PMID- 18044298
TI  - Radiology physics--where to now?

PMID- 18044297
TI  - Does epidural increase the incidence of cesarean delivery or instrumental labor
      in Saudi populations?
AB  - BACKGROUND: This is a retrospective review of the medical records of 861 patients
      admitted for vaginal delivery. Patients were randomized to either epidural
      analgesia or other analgesic methods of pain relief for labor pains. The primary
      purpose of this study was to evaluate the effect of epidural analgesia on the
      rate of cesarean section delivery. METHODS: 861 patients were admitted to Saad
      Specialist Hospital for vaginal delivery between May 1, to September 30, 2006.
      Patients were divided into Nulliparous (334 patients) and Multiparous (527
      patients) populations. Each population was then divided into two groups, epidural
      and non-epidural group. Epidural analgesia was initiated by a bolus of
      bupivacaine 0.25% (6 to 10 ml) plus fentanyl (50 to 100 microg), followed by
      bupivacaine 0.125% plus fentanyl (1 to 2 microg/ml) at the rate of (6 to 12
      ml/h). Non-epidural analgesia was initiated by one or mixture of I.M meperidine
      50 to 100 mg I.M, promethazine hydrochloride 25 mg, or Ontonox inhalers. RESULTS:
      In the Nulliparous population a total of 57 patients requested epidural (the
      epidural gp), while 277 patients received other analgesic methods (the non
      epidural gp). There was no difference in the rate of cesarean section deliveries
      between the two analgesia groups (12 patients of 57 in the epidural group
      (21.1%), versus 61 patients of 277 (22%) in the non-epidural gp). In the
      Multiparous population, a total of 49 patients requested epidural analgesia
      (epidural gp), while 478 patients received other analgesic methods (the non
      epidural gp). There was no difference in the rate of cesarean section deliveries
      between the two analgesia groups (5 of 49 patients (10.2%) in the epidural group
      compared to 39 of 478 patients (8.2%) in the non-epidural gp). Significantly,
      more patients in the epidural group had forceps or vacuum assisted deliveries
      compared to the other analgesia group (the non-epidural gp). This was evident in
      both the Nulliparous population (7 of 57 patients in the epidural gp (12.3%)
      compared to 13 of 277 patients (4.7%) in the non-epidural gp, p<0.05), and in the
      Multiparous population (4 of 49 patients (8.2%) in the epidural gp versus only 6
      of 478 patients (1.3%) in the non-epidural gp, p<0.005). Patients in the epidural
      gp had significantly lower pain scores compared to the other analgesia gp.
      Nulliparous reported lower pain scores during the first stage (epidural 2 +/- 2
      vs non-epidural 5 +/- 4, p<0.0001) and second stage of labor (epidural 3 +/- 3 vs
      non-epidural 6 +/- 3, p<0.0001). Multiparous scores were (epidural 2 +/- 2 vs non
      epidural 4 +/- 3, p<0.0001) in the first stage and (epidural 3 +/- 3 vs non
      epidural 5 +/- 4, p = 0.0007) in the second stage. Higher satisfaction rates were
      reported in epidural groups versus the non-epidural groups. 80% of Nulliparous
      women who received epidural rated their satisfaction as excellent or good versus
      45% in the non-epidural group p<0.001. In the Multiparous population 77% in the
      epidural versus 43% in the non-epidural groups p<0.001 reported excellent to good
      satisfaction rates. CONCLUSION: Epidural analgesia is an effective method of pain
      relief during labor compared to the other analgesic methods of labor pain relief,
      and it does not increase the incidence of cesarean section deliveries.

PMID- 18044299
TI  - Radiation protection in Australia: a thirty year perspective.
AB  - This review charts the changes in radiation protection philosophy, regulation and
      practice over the thirty year period 1977-2007. During this time there have been
      substantial changes both internationally and in Australia. Medical physicists
      have been involved, and continue to be involved, in all aspects of radiation
      protection in medicine at a national, State and hospital level.

PMID- 18044300
TI  - Technical developments in radiology in Australasia dating from 1977.
AB  - This article outlines the enormous technological advances that have taken place
      in the practice of radiology in Australasia in the 30 years since approximately
      1977. These developments have led to significant improvements in image quality
      across all modalities, including even general radiography, which had as its
      genesis Roentgen's ground-breaking discovery of X-rays in 1895. However, nowhere
      has the development been more dramatic than in magnetic resonance imaging (MRI).
      This may be brought into stark reality by noting that the first MRI image of a
      human finger was produced in 1976 followed one year later by that of a human
      chest and the first MRI units were not installed in Australia and New Zealand
      until 1986 and 1991, respectively. The quality of these early images would be
      judged as laughable by today's standards where the impressive isotropic imaging
      that can be achieved at sub-millimetre level by both MRI and CT could not have
      been dreamed of 30 years ago. The review also highlights some challenges for the
      future of the medical physics profession.

PMID- 18044301
TI  - Thermoluminescence dosimetry for in-vivo verification of high dose rate
      brachytherapy for prostate cancer.
AB  - It was the aim of the study to verify dose delivered in urethra and rectum during
      High Dose Rate brachytherapy boost (HDRBB) of prostate cancer patients. During
      the first fraction of HDRBB measurement catheters were placed in the urethra and
      rectum of prostate cancer patients. These contained LiF:Mg,Ti Thermoluminescence
      Dosimetry (TLD) rods of 1 mm diameter, with up to 11 detectors positioned every
      16 mm separated by radio-opaque markers. A Lorentzian peak function was used to
      fit the data. Measurements from 50 patients were evaluated and measured doses
      were compared with predictions from the treatment planning system (Plato Vs 13.5
      to 14.1). Prospective urinary and rectal toxicity scores were collected following
      treatment. In more than 90% of cases, the Lorentzian peak function provided a
      good fit to both experimental and planning urethral data (r2 > 0.9). In general
      there was good agreement between measured and predicted doses with the average
      difference between measured and planned maximum dose being 0.1 Gy. No significant
      association between dose and any clinical endpoints was observed in 43 patients
      available for clinical evaluation. An average inferior shift of 2 mm between the
      plan and the measurement performed approximately 1 hour after the planning CT
      scan was found for the dose distribution in the cohort of patients for the
      urethra measurements. Rectal measurements proved to be more difficult to
      interpret as there is more variability of TLD position between planning and
      treatment. TLD in-vivo measurements are easily performed in urethra and rectum
      during HDR brachytherapy of prostate patients. They verify the delivery and
      provide information about the dose delivered to critical structures. The latter
      may be of particular interest if higher doses are to be given per fraction such
      as in HDR monotherapy.

PMID- 18044302
TI  - Peristaltic transport of small particles--power law fluid suspension in a
      channel.
AB  - Peristaltic motion of a non-Newtonian, incompressible power law fluid with
      suspension of small particles in a two-dimensional channel is analyzed. A
      perturbation method has been employed to obtain the solution of the problem under
      the long wavelength approximation. The formation and growth of trapping zone are
      explained for variations in amplitude ratio and volume flow rate. The phenomenon
      of reflux has been studied. The behaviour of the axial velocity of fluid and
      solid particles has been discussed. The speed of the suspended particles is
      observed to be less than that of the fluid particles.

PMID- 18044303
TI  - Computed tomography phantom for radiochromic film dosimetry.
AB  - To evaluate in detail the dose distribution during computed tomography (CT), a
      sheet roll CT dosimetry phantom (SRCT-P) with a radiochromic film (RF) was
      experimentally developed. The SRCT-P was made by rolling up a vinyl chloride
      sheet in a cylindrical shape to arbitrarily select the SRCT-P diameter, dose
      measurement position, and depth. The SRCT-P centre core consisted of a plastic
      hose in which a 10 mm acrylic bar with a RF was inserted. To determine the
      availability of the SRCT-P, the surface and centre doses (at a 5 mm radius) at
      each SRCT-P diameter (6-16 cm; every 2 cm) were measured. The ratios of the
      centre-to-surface doses (D(centre)/D(surface)) systematically increased, from 80
      to 111%, for decreasing SRCT-P diameters, between 16 and 6 cm, respectively. The
      centre dose approached the surface dose as the SRCT-P diameter decreased. To use
      a RF for a CT dose measurement, further detailed research and analysis is
      necessary. However, this study has shown that a SRCT-P is useful and beneficial
      for the measurement of the dose distribution during a CT examination.

PMID- 18044304
TI  - A cortical-bone structural geometry phantom: dental plaster as a convenient and
      radiologically similar fabrication material.
AB  - Areal bone mineral density (aBMD), derived from dual-energy X-ray absorptiometry
      (DXA) scanners is used routinely to infer bone strength. With DXA hip scans there
      is growing acceptance of the advantages of also measuring bone structural
      geometric variables, that complement conventional aBMD to improve understanding
      of bone modelling, remodelling and processes of metabolic bone disease. However,
      phantoms for assessing structural geometric variables from DXA scans are not
      widely available, unlike those for aBMD. This study describes the development of
      such a phantom, simulating the cortical shell of the human femoral neck, using
      dental plaster as a material radiologically similar to cortical bone. The mass
      attenuation coefficient of the dental plaster differed by < 1% from cortical
      bone, over the relevant energy range. Performance testing was carried out with
      DXA, to determine accuracy and precision of the phantom structural geometry,
      using its dimensions and composition as 'gold standards'. Accuracy and precision
      of cortical structural geometry were poor when measured in a simulated 1 mm-thick
      osteoporotic cortex (5.5% precision and 50% accuracy errors), but improved with
      increasing cortical thickness. This study demonstrates the limitations of DXA
      based Hip Structure Analysis when applied to femora with thin cortices, and
      indicates improvements in the design of a phantom to better simulate such
      cortical structures.

PMID- 18044305
TI  - Respiratory regularity gated 4D CT acquisition: concepts and proof of principle.
AB  - Four-dimensional CT images are generally sorted through a post-acquisition
      procedure correlating images with a time-synchronized external respiration
      signal. The patient's ability to maintain reproducible respiration is the
      limiting factor during 4D CT, where artifacts occur in approximately 85% of scans
      with current technology. To reduce these artifacts and their subsequent effects
      during radiotherapy planning, a method for improved 4D CT image acquisition that
      relies on gating 4D CT acquisition based on the real time monitoring of the
      respiration signal has been proposed. The respiration signal and CT data
      acquisition are linked, such that data from irregular breathing cycles, which
      cause artifacts, are not acquired by gating CT acquisition by the respiratory
      signal. A proof-of-principle application of the respiratory regularity gated 4D
      CT method using patient respiratory signals demonstrates the potential of this
      method to reduce artifacts currently found in 4D CT scans. Numerical simulations
      indicate a potential reduction in motion within a respiratory phase bin by 20-40%
      depending on tolerances chosen. Additional advantages of the proposed method are
      dose reduction by eliminating unnecessary oversampling and obviating the need for
      post-processing to create the 4D CT data set.

PMID- 18044306
TI  - On the use of Kodak CR film for quality assurance of needle loading in I-125 seed
      prostate brachytherapy.
AB  - Low dose rate brachytherapy using implanted I-125 seeds as a monotherapy for
      prostate cancer is now in use in many hospitals. In contrast to fractionated
      brachytherapy treatments, where the effect of incorrect positioning of the source
      in one treatment fraction can be diminished by correcting the position in
      subsequent fractions, the I-125 seed implant is permanent, making correct
      positioning of the seeds in the prostate essential. The seeds are inserted into
      the prostate using needles. Correct configuration of seeds in the needles is
      essential in order to deliver the planned treatment. A comparison of an
      autoradiograph obtained by exposing film to the seed-loaded needles with the
      patient treatment plan is a valuable quality assurance tool. However, the time
      required to sufficiently expose Kodak XOMAT V film, currently used in this
      department is significant. This technical note presents the use of Kodak CR film
      for acquisition of the radiograph. The digital radiograph can be acquired
      significantly faster, has superior signal-to-noise ratio and contrast and has the
      usual benefits of digital film, e.g. a processing time which is shorter than that
      required for non-digital film, the possibility of image manipulation, possibility
      of paper printing and electronic storage.

PMID- 18044307
TI  - Continuing professional development needs of Australian radiation oncology
      medical physicists--an analysis of applications for CPD funding.
AB  - In November 2004, the Australian federal government allocated $775,000 to
      individual Australian radiation oncology medical physicists (ROMPs) to access
      continuing professional development (CPD) activities. The funding was
      administered by the Australasian College of Physical Scientists and Engineers in
      Medicine (ACPSEM). In order to receive funding, individuals had to submit an
      application to ACPSEM, which assessed each application and distributed funds to
      successful applicants. 248 separate applications were received from 143
      individuals in two rounds of applications. Information from the applications was
      collated and analysed, with the aim of identifying patterns that will be of use
      in future planning for CPD. This paper presents a summary of the information
      extracted from the analysis.

PMID- 18044308
TI  - [Doppler hemodynamic study in evaluation of liver metastases].
AB  - The color Doppler spectral analyses can be usefully in description of the liver
      circulation as one from non-invasive methods. Using color Doppler B mod
      ultrasound (Toshiba Core Vision) with duplex ultrasound we founded difference in
      liver circulation between patients with colon cancer and liver metastasis in
      comparison with those without metastases. We suggested this non invasive method
      for early detection of occult liver metastasis presence.

PMID- 18044309
TI  - [Lead point as a poor prognostic factor in the therapy of invagination in
      children].
AB  - Invagination is specific form of bowel opstruction that is seen in 1-4 children
      per 1000 births, usually in the period from 3 to 12 months of age. In 90-95 %
      reason for invagination in unknown so we called this forms idiopathic. In 5-10%
      invagination is caused by specific leading point. THE AIM of this retrospective
      study was to determinate prognostic valye of used biochemical tests (hemograms,
      glucosa, electrolites ( levels of Na+, K+, Ca+ and Cl-) and to prove bad
      influence of existing "leading point" in therapy of invagination (weather it will
      be surgical or hydrostatic desinvagination). METHODS: We analised 65 patients
      with invagination. We devided all our patients into 2 groups: first group
      consisted patients with idiopathic forms of invagination, and the other one were
      patients with invagination coused by specific leading point. RESULTS proved that
      leading point in invagination has great implications on clinical presentation,
      laboratory results, diagnostic and therapeutic procedure, and finaly in
      prognosis.

PMID- 18044310
TI  - [Comparison of granisetron and metoclopramide for prevention of nausea and
      vomiting following total cystectomy and ileal conduit].
AB  - The objective of this study was to examine the use of granisetron in actual
      clinical practice and to compare effect of dose of 1 mg granisetron after total
      cystectomy plus ileal conduit with group of patients which received
      metoclopramide. Granisetron established total contol of PONV in 93,33% patients.
      Granisetron is 40% more effective in PONV control than metoclopramide. Only
      minimal nausea epizodes were observed in early postoperative period in patients
      who had received low dose of granisetron (1 mg i.v.).

PMID- 18044311
TI  - [Relation of surgical results and proposed skull base meningioma grading system:
      analysis of clinical series with 42 patients].
AB  - Anatomical localisation of skull base meningioma link, their growth and relations
      with neurovascular structures reduce possibility for radical operation, and
      offten request additional preoperative or postoperative radiotherapy. We compared
      personal results of extent surgical resection and skull base meningioma treating
      outcome with predispose factors scale for surgical radicality and postoperative
      outcome. We present 42 patients, who were operated in Institute of neurosurgery
      CCS during the period from 2004 to 2006. RESULTS: Radical resection was possible
      in 29 cases, and in 13 cases reduction of tumor mass has been performed.
      Statistical significant predispose factor for radical resection were: absance of
      preoperative radiotherapy, intact functions of n.III, n.VI, tumor borders inside
      one skull base fossa and outside of magistral blood vessels. Karnofsky index at
      the end of following period statistical significant higher in patients with
      radical resection of skull base meningeioma. Preoperative radiological finding is
      singificant guide in planning of therapeutic protocol for skull base meningioma.
      Growth of tumor and relation with neurovascular structures restrict extent of
      resection and often request additional postoperative radiotherapy or reoperation.

PMID- 18044312
TI  - [Reconstruction of the alae nasi by folded nasolabial flap].
AB  - Reconstruction of the nose is very old surgical procedure and, in fact,
      represents the beginnings of plastic surgery. In reconstruction, an effort has to
      be made in order to achieve a normal look. A surgeon must choose carefully the
      method of reconstruction, taking into consideration the skin color, texture and
      nasal topography. Full-thickness nasal defects in alar region are very difficult
      for reconstruction due to anatomic characteristics and structures, which are very
      important for normal breathing and cosmetic result. Our study analyzed 16
      patients with full-thickness defect of alae nasi. Folded nasolabial flaps were
      used for reconstruction of these defects. Good results were achieved in all
      cases. The flap was vital. No flap necrosis was reported in any of these
      patients. The lining of the nose was good. Postoperatively, the alar edge was
      thickened, but it became thinned after six months. The incision in donor's region
      was well placed in the natural line of nasolabial fold. It was concluded that
      folded nasolabial flap was extremely good one-step procedure for reconstruction
      of full-thickness defects of alar region.

PMID- 18044314
TI  - [Therapeutically effect of the physical procedures on the elbow contractures in
      children with supracondylar humerus fractures].
AB  - Supracondylar humerus fractures are the most common fracture around the elbow in
      the pediatric population. These fractures in children may lead to functional
      disturbance with loss or reduction of range of motion in the elbow joint. The aim
      of this study was to investigate the effect of the physical therapy on the range
      of the motion of the elbow joint in the post-traumatic elbow contractures in the
      childhood after supracondylar fractures. We analyzed in this research 34 children
      (average age 8.57+/-2.94 years) with elbow contractures that were treated by
      physical therapy after orthopedic treatment. Functional outcome was presented in
      degree from 1 to 3 (Flynn). The difference in the grade at the beginning and the
      end of the therapy is statistically significant (t=16.38, p<0.001). 91.18 %, of
      the children had excellent result. Complex of various therapeutically physical
      procedures can significant improve range of motion of the elbow joint.

PMID- 18044313
TI  - [Treatment of femoral shaft fractures in polytrauma patients using Mitkovic type
      internal fixator].
AB  - Polytrauma remains a major social, economic and medicine affliction. Successful
      surgical treatment of polytrauma patient's requires an approach predicated on
      prioritizing injuries. An isoleted fractures rarely poses any threat but in
      association with multiple injuries, a fractures assumes greater significance.
      Proper management of femur fractures in po-lytrauma can gretly reduce the
      mortality and morbidity. In this work the results of the operative treatments of
      the femoral shaft fractures in polytrauma patients using Mitkovic type internal
      fixator (14 patients) and Kuntscher nail (9 patients) are compared. The average
      patients age was 28.43 years (range 16 to 61). Internal fixation using Mitkovic
      type internal fixator can be method of choose in treatment of femur fractures in
      polytrauma patient's. Its application is relatively simple. It doesn't damage the
      periosteal and meduullary bone vascularization, which favors osteosynthesis and
      provides considerable contribution in osteogensis.

PMID- 18044316
TI  - Compliance and capacity of the normal human rectum--physical considerations and
      measurement pitfalls.
AB  - The assessment of parameters which adequately represent rectal and neorectal
      compliance is complex. Biological properties of the rectum during distension and
      relaxation show significant departures from in vitro physical compliance
      measurements; as much dependent upon the viscoelastic charateristics of hollow
      organ deformation as upon the technique of compliance calculation. This review
      discusses the pressure/volume characteristics of importance in the rectum during
      distension from a bioengineering perspective and outlines the disparities of such
      measurements in living biological systems. Techniques and pitfalls of newer
      methods to assess rectal wall stiffness (impedance planimetry and barostat
      measurement) are discussed.

PMID- 18044315
TI  - Retroperitoneal endoscopic adrenalectomy vs. conventional adrenalectomy in
      treatment of benign adrenal lesions--comparative analysis.
AB  - Minimally invasive adrenalectomy is considered to be the standard of care for the
      surgical treatment of the adrenal gland' s pathology. Since the initial report of
      laparoscopic adrenalectomy in 1992 and of retroperitoneal endoscopic
      adrenalectomy in 1994, it has evolved into a feasible and safe minimally invasive
      procedure for benign adrenal tumors. Clinical characteristics and outcomes of 63
      retroperitoneal endoscopic adrenalectomies (REAs) and 45 conventional
      adrenalectomies (CAs) from 1996 to 2004 were evaluated. 61 patients underwent 63
      REAs. Tumor size varied from 2 to 8 cm. Median age was 48.6 years. Median
      operative time was 135 min (45-240), median intraoperative blood loss - 85 ml (30
      550). The complication rate was 17.77%. Median postoperative hospital stay was 5
      days (2-10). 44 patients underwent 45 conventional adenalectomies. Median age was
      44.5 years (16-71). Intraoperative complication rate was 17.77%, postoperative 
      22.22 %, Median operative time was 120 min (75-240). Median postoperative
      hospital stay was 10 days (6-21). No statistically significant difference was
      established between median operative times of REA- and CA-groups (p=0.91).
      Conventional adrenalectomy was associated with a significantly increased
      complication rate (p= 0.009). Hospitalization was also longer after the open
      tecnique (d). Introduced in 1994 and displaying all advantages of minimal access
      surgery REA has become the standard of care for benign adrenal tumors.

PMID- 18044317
TI  - Olfactory groove meningiomas.
AB  - Meningiomas, usually histologically benign tumors, are originating from the
      arachnoidal cap cells normally present intracranially in varying sites. Olfactory
      groove meningeomas arise from the medline of the anterior fossa between the
      crista galli and the tuberculum sellae. The most common presenting symptoms are
      the visual field defects, epilepsy, and psychological change. They are often
      large before they are detected because of slowly asymptomatic growing in the
      interhemispheric space of the frontal lobes. This series is consisted of 29
      patients suffering from olfactory groove meningiomas treated surgicaly between
      May 1992 and November 2003. The surgical results and complications are presented
      and analized, comparing them by the other reported series.

PMID- 18044318
TI  - Congenital anomalies of the mesonephric duct and fertility.
AB  - Agenesia of deferential duct and the others congenital malformations of
      mesonephronical duct are often encountering condition in andrological practice.
      This study presents the possibilities of reproductive medicine to restore the
      male fertility and concentrates on biological and clinical aspects of
      malformations of mesonephronic duct like factors for excretory male infertility.
      The investigations including 104 patients (mean age 30.25+/-1.91 years old) with
      congenital anomalies of mesonephronical duct with: Agenesia of mesonephronical
      derivates - case with unilateral agenesia of the deferent duct, kidney and left
      urether (n=1); Dysgenesia of the epididymis (n=5); Cysts of the epididymis
      (n=47); Agenesia of the deferential duct (n=48); Aplasia of the eja-culatorial
      duct (n=3). The following methods were used: open testicular biopsy by Vilar;
      objective findings in situ operation; bilateral epididymo - and
      deferentovesiculography; morphological specimens of the testicular and epididymal
      tissues; enzymohistochemical analysis of testicular specimens; the ejaculates and
      morphological analysis of spermatozoa were assessed for quality parameters by the
      standard protocol; enzymocytological research of spermatozoa in seminal fluid;
      biochemical analysis of seminal fluid fructose and citric acid concentrations;
      radioimmunoassay for measurements of blood FSH and testosterone concentration.
      RESULTS: Most often observed localization of the malformations of mesonephronic
      canal is bilateral at 54.81%. The testicular specimens proved preserved
      testicular architecture and spermatogenesis, and the epididymal slides showed
      dilatation of the epididymal tubules, which were overfilled with a lot of
      spermatozoa. The strongest expression of the enzymichistochemical NADH-TR
      reactions is in the Sertoli cells. We observed spermatozoa with disrup-ted
      configuration among which the abnormalities in sperm head and acrosome were
      predominated. The biochemical analysis of seminal fluid proves normal citric acid
      and low or lack of fructose concentration in seminal fluid. There were no
      breaches in endocrine regulation of the reproductive process. Patients with
      congenital anomalies of mesonephronic canal have preserving fertility in 31.73%.
      There are morpho-functional disorders of the testes, epididymis and seminal ducts
      in 68.27%. CONCLUSION: There are normal spermatogenesis but definite sterility.
      These results necessitate an application of plastic reconstructive operation for
      recovery of fertilizing ability of the patients, or their involvement in ICSI
      programme.

PMID- 18044319
TI  - [The role of functional sinus surgery for treatment of antrochoanal polyp].
AB  - Antrochoanal polyp (ACP) is a benign lesion which arises from the mucosa of
      maxillary sinus, fills it and expands through natural ostium towards choana
      protruding in the epipharynx. OBJECTIVE: to present our experience in endoscopic
      surgery of ACP. MATERIAL AND METHODS: prospective study included 24 patients
      operated at the Institute of Otorinolaryngology and Maxillofacial surgery,
      Clinical Center of Serbia, Belgrade, in the period 2002-2004. Subjective
      symptoms, endoscopic and CT findings were evaluated postoperatively, following up
      the patients in the period 12-20 months. Subjective difficulties of patients were
      tested by 100mm-analogue scale, while endoscopic and CT findings were
      demonstrated by three-stage scale from 0 to 2. Applying the technique of ACP
      extraction in Trendelenburg's position and approaching the part which protrudes
      in the epipharynx, we successfully removed the endonasal part by means of curved
      forceps for epipharyngeal biopsy. By endoscopic middle meatotomy, the natural
      ostium of maxillary sinus was expanded and pathological process from the very
      sinus was successfully removed. RESULTS: only one female patient had the majority
      of symptoms after the operation, while all others had no complaints. Endoscopic
      and CT findings were normal in all patients at the latest control, without any
      signs of ACP recurrence. There were no intraoperative or postoperative
      complications. CONCLUSION: minimal damage to sinus mucosa due to forceps is
      lesser problem than complications developed upon creating even the miniature
      opening in the canine fossa. Using this technique, a dexterous surgeon may
      successfully extract patho-logical process with minimal incidence of recurrence,
      and, more important, with no complications and maximally fast recovery of
      patients.

PMID- 18044320
TI  - [Amputation of the lower eyelid in the therapy of eyelid tumors].
AB  - In carefully selected cases of tumors of the lower eyelid (tumors which destroy
      more than 40% of the eyelid margin and are not higher then 3 mm, in old patients
      in bad general condition and in the cases of multiple microrecurrences of a
      tumor) authors suggest simple excision of a tumor without reconstruction of a
      eyelid. It is an effective method of treatment of the tumor with good functional
      effects and acceptable cosmetic results.

PMID- 18044321
TI  - [Endometriosis in cesarean section surgical scar].
AB  - INTRODUCTION: Endometriosis is the presence of endometrial glands and stroma
      outside of uterine cavity. It may occur in the abdominal wall scar after the
      operation in which uterus was opened. In cesarean section scar it occurs in 0.4%.
      It is in 2/3 patients characterised with triad of: tumor, periodic pain
      associated with menses and history of cesarean section. The mechanism of
      endometriosis occuring in the cesarean scar is felt to be secondary to iatrogenic
      transplantation of endometrium or extrauterine decidual tissue into the incision
      during the cesarean section. CASE OUTLINE: Forty years old patient with tumor
      4,5x4 cm that appeared in abdominal wall scar one year after second cesarean
      section, followed by periodic pain and macroscopic changes associated with
      menses. First diagnosis was granuloma in the surgical scar, but as she had
      periodic simptoms, diferential diagnosis was endometriosis. Hormonal therapy with
      contraceptiv drugs was ordered. As it was no improvement she was operated. The
      surgical excision of the tumor including fascia and muscle tissue was done.
      Sample revealed endometrium after histopathologic examination. Patient was
      complitely recoverd and without relepse of simptoms during followup to date.
      CONCLUSION: When there is a tumor in the cesarean section scar or scar after the
      operation in which uterus or ovarial tube was opened, followed with periodical
      pain and macroscopic changes associated with menses, endometriosis should be
      considered. Surgical excision of the tumor is sufficient and patohistological
      examination confirms diagnosis.

PMID- 18044322
TI  - [Treatment of unstable closed tibial shaft fractures by external fixation].
AB  - The fracture of tibia shaft is one of the most common fracture of long bones. The
      authors bring out the results of the treatment of 90 patients with unstable
      closed tibial shaft fractures treated by the use of Mitkovic external fixation
      systems. Within the analayzed group there were 66 (73%) male and 24 (27%) female.
      The average patients age was 43.9 years (range 15 to 82). Excellent result in
      treatment of unstable closed tibial shaft fractures with external fixation were
      achieved in 15 (16,7%) patients, very good in 38 (42,2%) patients, good in 24
      (26,7%), poor in 9 (10%) and bad in 4 (4,4%) patients. With 4 (4,4%) patients
      pseudoarthrosis was formed. Additional treatment of patients with pseudoarthrosis
      (spongioplastic and placing of CD device) led to pseudoarthrosis healing. Within
      the analyzed group in all patients treated with extenal fixation there were no
      registered cases of postoperative osteitis. External fixation by the use of
      Mitkovic external fixation is one of the method of choose in the treatment of
      unstable closed tibial fractures, providing dynamic and balanced biomehanical
      conditions for fracture healing.

PMID- 18044323
TI  - Treatment of emergency surgical complications of kidney transplantations.
AB  - Surgical complications subsequent to the kidney transplantation are not
      infrequent and they are characterized by the high percentage of graft loss (596
      18% in standard surgical procedures and up to 37% in atypically performed
      transplantations). The study included 311 transplanted patients (206 (66.2%)
      living donors and 105 (33.8%) cadaver donors). Surgical complications developing
      during the immediate posttransplantation period as well as during the late period
      (after a year and a half) were classified as: I urinary complications; II
      vascular complications; III other complications. In majority of the cases urinary
      complications (urinary fistulas, ureteral obstructions, vesico-ureteral reflux)
      as well as other complications (cholecystopancreatitis and lymphocele) did not
      necessitate urgent treatment, unlike most of the vascular complications. All the
      vascular complications (29/311) developed during the immediate postoperative
      period, except for occurrence of arterial stenoses which ensued later on, while
      the development of symptoms was rapid. Severity of both symptoms and clinical
      picture necessitated urgent surgical re-intervention in order to preserve the
      graft and patient's life. Vascular complications were classified as: true
      vascular complications, hemorrhages and kidney ruptures in order to distinguish
      technical and other factors contributing to development of the complications.
      Onset of the true vascular complications related to the graft and recipient blood
      vessel changes was evidenced in 20 patients (69%/29 patients) while the incidence
      of hemorrhages and ruptures was considerably lower (14%/29 patients and 17%/29
      patients). As for the true vascular complications, vascular stem thrombosis
      subsequent to cadaveric transplantations was the most frequent, and
      transplantectomy was performed in all the cases in absence of any lethal
      outcomes. Two cases with iliac artery rupture resulted in graft loss subsequent
      to urgen exploration. In all cases with hemorrhages the applied therapy resulted
      in positive responses, except in one case in which massive gastrointestinal
      hemorrhage led to lethal outcome. The response to the urgent surgical treatment
      of spontaneous kidney graft ruptures was positive in 60% of the cases, while in
      the remaining 40% transplantectomy was necessitated due to the extensiveness of
      the lesion in order to preserve patient's life.

PMID- 18044324
TI  - ["I am sorry, I have bad news... "- principles in informing patients on the
      gravity of a disease and the treatment].
AB  - The discovery of the appearance of a serious disease, and the necessity for
      diagnostics, treatment and rehabilitation, particularly when malignity is
      involved, represents exceptionally stressful news for the patient and his family.
      Most often this is a task for the physician. In this paper the authors consider
      the meaning of bad news in unexpected life events which significantly disturb the
      individual psycho-social ballance of the patient, as well as the familly dynamics
      and structure. It presents a review of available literature on the subject of the
      definition of so-called "bad news", the development of approaches in
      announcement, and current practical approaches and models which assist physicians
      in helping suffering patients in professional and humane ways. It points out
      inadequacies in the education of phisicians for this kind of task, and the
      variety of approaches. With the aim of improving the education of phisicians, and
      especially clinicians in surgical fields, the authors recommend a number of
      educational programs: education in the area od psychological and psychiatric
      aspects of learning of a serious disease, including acute reactions such as
      depressive states, reactive psychotic states, consumption of alcohol, etc.;
      education in the area of the family life cycle, and the effect of the disease as
      an unexpected life crisis on the family dinamic; education in the area of
      fundamental principles of psycho-and pharmaco-therapy, as well as the provision
      of support to the patient and his familly; training in the skills of announcing
      bad news to the patient and his familly through the explanatory presentation of
      the case and supervised simulation of sessions.

PMID- 18044325
TI  - [Medicolegal aspects in gastroenterology].
AB  - INTRODUCTION: Medical practice is under continual public scrutiny. There are
      increasing concerns on medical malpractice and its consequences - further
      deterioration of health and death. Public criticism of medical practice very
      often outrageous, but sometimes medical negligence is obvious. AIM OF THE STUDY:
      We are presenting basic medicolegal analysis of causation in cases of medical
      malpractice with subsequent fatal outcome. CASE STUDY: We are reporting on two
      cases from archives of Institute of Forensic Medicine. The selected cases
      (biliary ileus and pseudomembranous colitis subsequent to elective
      cholecistectomy) may reflect common gastroenterological pathology. The analysis
      of medical practice and its consequences, i.e. analyse of causation has been
      presented and commented in regard to the pertinent legislation. CONCLUSION:
      Doctors ought to be familiar with medicolegal aspects of their practice. This
      might affect them to improve the quality of health care, and to increase
      protection, both of health care personal and patients.

PMID- 18044326
TI  - [Current opinion in epidural analgesia influence on incidence of complications
      after major abdominal surgery].
AB  - Review article summarizes current knowledge of general and epidural anaesthesia
      combination for major abdominal surgery and incidence of postoperative
      complications. Continuous epidural local anaesthetics especially through thoracic
      placed epidural catheter decrease opioids use and as part of "acute
      rehabilitation" plays important role in postoperative recovery. Most of the
      studies showed tion is not dependent on kind of anaesthesia and analgesia.
      Successfully treated postoperative pain prevents chronic postoperative pain,
      which is best achieved in abdominal surgery with thoracic epidural use.

PMID- 18044327
TI  - [Perspective of mechanical ventilation of lungs].
AB  - Mechanical ventilation of lungs during the long history has gone through
      different phases, which have been associated with technological and scientific
      development of its time. This is the most complex process and in spite of many
      progress it does not solve all problems, maintained of respiratory homeostasis,
      especially in patients with difficult lungs damage. Therefore, there is an
      existing need for further development of mechanical ventilation of lungs. Over
      the past time, a number of innovative approaches or adjuncts to mechanical
      ventilation have been actively researched. Many of these have shown some promise
      in improving our ability to provide ventilatory support. Which of these
      innovations will outlast the future? Based on actual development at innovations
      of mechanical ventilation, it can be assumed that it will be: protective lung
      ventilation, special form of gas exchange, weaning from mechanical ventilation,
      noninvasive and home use ventilators, development in fallowing patient's
      condition and pharmacotherapy development.

PMID- 18044328
TI  - Primary adrenal hydatid cyst: a case report.
AB  - A rare case of primary adrenal hydatid cyst is reported in a 56-year-old male.
      The cyst was discovered incidentally. The only symptom was hypertension. Partial
      excision of the gland and pericystectomy were performed. Surgical treatment was
      also therapeutic for the hypertension.

PMID- 18044329
TI  - Allantoic remnants presenting as a giant retroperitoneal cyst.
AB  - Urachal anomalies are usually found in early childhood or just after birth. These
      usually involve patent ductus urachus, urachal cyst, umbilical-urachal sinus or
      vesicourachal diverticulum. Very rarely are urachal anomalies found in adults,
      usully as an infected urachal cyst. We are presenting a case of surgically
      removed giant urachal retroperitoneal cyst that was found by chance during the
      abdominal ultrasound examination of a 22 year old man who was initially treated
      for idiopathic hypertension.

PMID- 18044330
TI  - A case of transitional cell bladder carcinoma prolapsed from the external
      urethral orifice: a 6-year follow-up after percutaneous suprapubic bladder.
AB  - A 30-year-old female was admitted in emergency with acute urinary retention due
      to bladder tumour prolapsed from the external urethral orifice. The patient
      underwent immediate endoscopic surgery via suprapubic percutaneous approach. The
      histological examination confirmed a superficial highly differentiated
      transitional cell bladder carcinoma. During the 6-year follow-up no evidence of
      local recurrence or metastatic tumour spread was revealed. The comprehensive
      Medline search confirmed that this is the fourth case of bladder tumour prolapsed
      from the external urethral orifice, reported so far. The case deserves the
      interest of practising urologists because of the exceptional rarity of the entity
      and the unconventional treatment approach which involves using a percutaneous
      suprapubic endoscopic technique. Based on the results achieved, we can recommend
      this unconventional endoscopic approach as specifically indicated in certain
      situations.

PMID- 18044331
TI  - [Massive GIST of the stomach--case report].
AB  - Gastrointestinal stromal tumors (GIST) are rare mesenchimal neoplasmas of the
      gastrointestinal tract. The diagnosis of this tumors are oftenly very difficult.
      Patients with this tumor are ussualy addmited to the hospital cause of the
      gastrointestinal bleeding, abdominal pain, abdominal distension, disphagia,
      obstructive jaundice and bowel obsstruction. In this case report, we present a 86
      year old patient with massive GIST of the stomach which was not preoperatively
      diagnosed.

PMID- 18044332
TI  - Evaluation and management of traumatic rupture of the corpus cavrnosum.
AB  - Fracture of the penis, or rupture of the corpus c avernosum is an uncommon
      injury, but probably under-reported entity. Only approximately 180 cases have
      been reported in the literature. Penile fracture with urethral injury is even
      more uncommon, accounting for approximately 10 to 20% of the cases reported.
      Early reports on this injury suggest conservative therapy as the choice of
      treatment. Recent reports emphasize immediate surgical repair to prevent late
      sequelae of injury, especially those associated with urethral rupture. We review
      5 cases with evaluation, treatment and followup. Delays in treatment lead to long
      term complications.

PMID- 18044333
TI  - [The role of the magnetic resonance in diagnosis of multiple myeloma].
AB  - Multiple myeloma comprises syndromes and specific laboratory findings associated
      with monoclonal proliferation of plasmocytes usually secreting monoclonal
      protein, ultimately leading to the bone destruction. One of the main diagnostic
      methods is conventional X-ray of the skeleton. Assessment of bone destruction is
      mandatory to order a patient to Salmon and Durie clinical staging system.
      Magnetic resonance (MR), especially sequences surveying the whole skeleton, is
      the most precise diagnostic tool in imaging of bone marrow and pathologies
      within. It is a more sensitive, specific and safer method than conventional
      radiography, which is particularly suitable for detection of secondary osteolytic
      changes Pattern and intensity of infiltrations in MR is an independent prognostic
      factor and has been implemented in the modernized clinical staging of multiple
      myeloma. Similarily, resolution of infiltration in MR due to the treatment is
      considered as independent prognostic factor. Due to its multiple advantages MR
      should be a settled diagnostic standard in multiple myeloma.

PMID- 18044334
TI  - [Influence of the radiofrequency current on the left ventricular systolic
      function].
AB  - Radio frequency catheter ablation (RFCA)--induced myocardial injury is caused by
      the thermal, electrical and biological effects of RF current. AIM OF THE STUDY:
      To assess the changes in the left ventricular systolic function following RFCA.
      MATERIAL AND METHODS: Ejection fraction (EF) and shortening fraction (FS) were
      assessed in 24 pacing patients (10 females in age 44-79 years, mean age 64.8 +/-
      11 years) before and 24 hours after successful RFCA of an atrio-ventricular node
      area due to medical refractory chronic atrial fibrillation. RESULTS: The mean
      number of RFCA applications was 5.5 +/- 5.0, total application time--237.5 +/-
      188 sec, cumulative energy--8916.7 +/- 6886.2 J and temperature measured at the
      tip of electrode--59.6 +/- 4.90 degrees C. We did not find the changes in EF and
      FS after the ablation. In addition, a non-significant correlation between the
      left ventricular systolic function and the cumulative RFCA energy was documented.
      CONCLUSIONS: Non-significant correlation between the left ventricular
      contractility and the cumulative RFCA energy was observed.

PMID- 18044335
TI  - [Laparoscopic cholecystectomy for acute cholecystitis].
AB  - Laparoscopic cholecystectomy is considered the "gold standard" for the planned
      treatment of symptomatic cholecystolithiasis. Currently this method is used in
      88% of cholecystectomy according to world database. There are evidences that
      laparoscopic cholecystectomy for acute cholecystitis is a quite safe method which
      is not connected with many complications. AIM OF THE STUDY: Assessment of the
      post-operative complication risk and hospitalization time in cases of acute
      cholecystitis had undergone laparoscopic cholecystectomy in comparison with
      classic cholecystectomy. Evaluation of non-specific inflammation process based on
      C-reactive protein (CRP) levels in patients' serum analysis. MATERIAL AND
      METHODS: Eighty patients (58 women and 22 men) aged 22-74 (mean 53.6) were
      included to the study. They were undergone cholecystectomy in the Department of
      Gastroenterological, Oncological and General Surgery because of acute
      cholecystitis. There were two groups of patients: 38 patients who underwent
      laparoscopic cholecystectomy (group I) and 42 patients who underwent "classic"
      cholecystectomy (group II). No statistical differences of clinical and
      demographic characteristics were found in the studied groups. There was also the
      third group of patients distinguished in the study - the control group of 42
      patients who underwent "planned" laparoscopic cholecystectomy because of chronic
      cholecystolithiasis. The patients were qualified for the groups I and II in
      accordance with randomization rule. The CRP-level of the patients' serum was
      evaluated in the group I and II twice: before and in the 2nd day after
      cholecystectomy. RESULTS: The mean operating time was significantly shorter in
      the group I (laparoscopic cholecystectomy) compared with the group II ("open"
      cholecystectomy) 63.24 and 86.31 minutes respectively (p < 0.05) and 58 minutes
      in the control group. The mean period of hospital stay was also significantly
      shorter in the group I (4.12 day) compared with the group II (7.19), (p < 0.05),
      however there was no statistically significant difference between group I and the
      control group (3.1 day). The level of serum CRP measured before surgery was not
      significantly different in groups I and II although in the 2nd day after the
      operation statistically significant difference between studied groups was
      obtained: patients who were undergone laparoscopy (group I) had a lower level of
      serum CRP. CONCLUSIONS: Laparoscopic cholecystectomy is a safe method of
      treatment both acute cholecystitis and chronic cholecystolithiasis.

PMID- 18044336
TI  - [Comparison of test with antigen VlsE (C6) with tests with recombinant antigens
      in patients with Lyme borreliosis].
AB  - In diagnosis of Lyme borreliosis classic, recombinant antigens are used.
      Introduced recombinant antigen VlsE increases hope to improve sensibility of the
      tests. AIM OF THE STUDY: Serological results detecting antibodies against
      Borrelia burgdorferi, recombinant antigens in both classes and test with VlsE
      were compared. MATERIAL AND METHODS: Quick ELISA C6 Borrelia Assay Kit (U.S.A.)
      for both classes simultaneusly were compared with two tests composed of
      recombinant antigens Borrelia IgG recombinant, Borrelia IgM recombinant
      (Biomedica, Austria)separate for IgM i IgG antibodies. Patients with borreliosis
      as eryhtema migrans were evaluated (n=36) and group with chronic Lyme arthritis
      (n=68). RESULTS: Statistical coincidence between results of test ELISA C6 and
      presence of antibodies IgM (p < 0.0001) and IgG (p < 0.0001) obtained in tests
      based on recombinant antigens in group erytema migrans. In group Lyme arthritis
      coincidence (p < 0.0002), with IgM antibodies was stated. CONCLUSIONS: Test ELISA
      C6 (with protein VlsE-C6) in group of patients with Lyme borreliosis had
      statistically essential predictive values of presence antibodies in IgM i IgG
      class, stated in tests performed separately for IgM and IgG classes with
      recombinant antigens. Tests based on conservative part of protein VlsE (C6),
      detecting antibodies in both classes are very promising in diagnosis of early
      stages Lyme borreliosis.

PMID- 18044337
TI  - [Cilliary neurotrophic factor in tick-borne encephalitis].
AB  - THE PURPOSE OF THIS STUDY: To evaluate concentrations of cilliary neutrophic
      factor (CNTF) in serum and cerebrospinal fluid of patients with tick-borne
      encephalitis (TBE) and bacterial meningitis. MATERIAL AND METHODS: 49 patients
      (14 females and 35 males), aged 19 to 62 were examined. Patients were divided
      into three groups: group I--23 patients (47%) with diagnosed TBE, group II--16
      patients (33%) with bacterial meningitis and 10 (20%) healthy individuals as
      control group. The examination was performed twice before and after 4-weeks
      treatment. In achieved results CNTF concentration in serum from group I and II in
      both examinations was significantly higher compared to control group. RESULTS:
      Patients with TBE showed higher serum CNTF concentration compared to group with
      bacterial meningitis in both examinations as well. In examination 1 cerebrospinal
      fluid CNTF concentration of both groups was significantly higher in comparison to
      control group. Examined cytokine CSF concentration was higher in group with
      bacterial meningitis. After treatment CNTF concentration decreased significantly
      in group I and II. In group I CNTF concentration was comparable to control group.
      CONCLUSION: Concentration of CNTF in csf could be used as a marker of the
      inflammatory process in the central nervous system.

PMID- 18044338
TI  - [Clinical forms of neuroborreliosis among hospitalized patients in the years 2000
      2005].
AB  - THE AIM OF THE STUDY: To evaluate the frequency of clinical forms as well as
      laboratory and neuroimaging results of patients with diagnosed neuroborreliosis
      in the years 2000-2005 due to neuroborreliosis. MATERIAL AND METHODS: The records
      of 125 patients at the age of 21-83 (mean 49 years) treated in the years 2000
      2005 in the Department of Infectious Diseases and Neuroinfections, Medical
      University, Bialystok were subject to retrospective analysis. Diagnosis was based
      on case history along with a clinical picture and presence of antibodies against
      Borrelia burgdorferi, using ELISA test (Borrelia IgM and Borrelia IgG recombinant
      Biomedica). The subject of the detailed analysis was demographic data, clinical
      symptoms as well as subjective complaints, results of neurological examinations,
      the results of cerebrospinal fluid (CSF) parameters and results of serologic
      tests. RESULTS: The most frequent clinical symptoms observed were: headaches 71%,
      vertigo 44%, meningeal symptoms 22% and neurological paresis 27% (including
      facial palsy--23%). Inflammatory changes in CSF in the form of increased proteins
      concentration and pleocytosis were present among 34% of patients. In all cases
      the antibodies against B. burgdorferi were present in CSF in diagnostically
      significant titer. Serum presence of antibodies antiborrelia IgM was found with
      55% of patients and anibodies antiborrelia IgG with 76% of patients. 17% of
      patients suffering from neuroborreliosis were also coinfected with tick-borne
      encephalitis virus. Along with the neurological symptoms, which were crucial to
      diagnosis, general symptoms coexisted, such as: weakness 35%, arthralgia 54% and
      nausea 17%. In the analyzed period of time neuroborreliosis was diagnosed in a
      13% of hospitalized patient suffering from borreliosis. CONCLUSIONS: Absence of
      erythema migrans does not exclude existence of neuroborreliosis. Symptoms that
      may suggest presence of neuroborreliosis are not only neurological symptoms such
      as facial palsy, but also memory and concentration disorders and general
      symptoms.

PMID- 18044339
TI  - [Polymorphism Lys751Gln of XPD gene and breast cancer risk in women].
AB  - Polymorphisms in DNA repair genes resulting in variation of DNA repair efficiency
      may therefore be associated with cancer risk. AIM OF THE STUDY: In the present
      work the distribution of genotypes and frequency of alleles of the Lys751Gln
      polymorphism of XPD gene in subjects with breast cancer were investigated.
      MATERIAL AND METHODS: Genomic DNA isolated from 92 breast cancer patients and
      control (n=110) was used to genotype XPD Lys751Gln by means of polymerase chain
      reaction and restriction fragment length polymorphism (PCR-RFLP) analysis.
      RESULTS: The distribution of the genotypes of the Lys751Gln polymorphism of XPD
      in both control and patients did not differ significantly (p > 0.05) from those
      predicted by the Hardy-Weinberg distribution. There were no significant
      differences (p > 0.05) in genotype distributions and allele frequencies between
      subgroups assigned to histological stage. CONCLUSIONS: The results suggest that
      the Lys751Gln polymorphism of XPD gene may not be linked with appearance and
      development of breast cancer.

PMID- 18044340
TI  - [The influence of delivery and perinatal risk factors on the concentration of
      cystatine C in umbilical cord blood].
AB  - Cystatin C--a low molecular protein, recognized as a sensitive marker of
      glomerular filtration rate and inhibitor of the lisosomal proteolitic enzymes in
      the organism. It is produced continuously and released to biological fluids. The
      concentration of cystatin C in the cord blood is higher and more diverse than in
      the peripheral blood with children and adults. THE AIM OF THIS STUDY: To
      determinate the range of the concentrations cystatin C in the umbilical cord
      blood and to research the influence of delivery and perinatal risk factors on
      concentration of cystatin C in cord blood. MATERIAL AND METHODS: The study
      included 444 newborns born by spontaneous deliveries and cesarean sections. In
      both subgroups, term neonates, preterm and some amount of newborns with
      additional perinatal risk factors (hipotrofia, infection, asphyxia) were found.
      Clinical evaluation, blood tests and USG examination were performed. Blood cord
      samples were analyzed entirely in the neonates with normal USG image of urinary
      tract was normal. RESULTS: The mean cystatine C concentration in umbilical cord
      blood were 1.65 +/- 0.44 mg/l. There were not differences in the mean cystatin C
      concentration between term and preterm newborns without additional risk factors.
      The most important factor influencing cystatin C concentration appeared to be the
      kind of delivery In neonates born by spontaneous delivery mean cystatin C
      concentration was significantly higher (1.82 mg/l) than in neonates born by
      cesarean sections (1.48 mg/l). Mean cystatin C concentration was strongly
      correlated with a lactic acid concentration and a length of delivery.
      CONCLUSIONS: Statistically higher concentrations of cystatine C were found in
      neonates born by spontaneous delivery. Laktacidemia is probably one of the
      factors responsible for elevation of cystatin C concentration in the cord blood.
      Higher cystatine C level can be recognized as a mechanism protecting the neonate
      from local or/and systemic proteolytic activity.

PMID- 18044341
TI  - [Effect of anthocyanins from Aronia melanocarpa on blood pressure, concentration
      of endothelin-1 and lipids in patients with metabolic syndrome].
AB  - THE AIM OF THE STUDY: To estimate the influence of anthocyanins from Aronia
      melanocarpa on blood pressure, concentration of endothelin-1 (ET-1), serum
      lipids, fasting glucose, uric acid and membrane cholesterol in erythrocytes of
      patients (pts) with metabolic syndrome (MS). MATERIAL AND METHODS: The study
      comprised 22 healthy volunteers and 25 pts with MS treated with anthocyanins (3 x
      100 mg/d) for 2 months. Waist circumference (> or = 80 cm for women and > or =94
      cm for men), triglicerydes (TG) level >150 mg/dl (1.7 mmol/l), cholesterol-HDL
      (HDL-C) level < 40 mg/dl (1.0 mmol/l) for men and <50 mg/dl (1.3 mmol/l) for
      women, systolic blood pressure (SBP) >130 mmHg and/or diastolic blood pressure
      (DBP) >85 mmHg were inclusion criteria for patients with MS. Before and after 2
      months of treatment the following parameters were determined: SBP, DBP, serum
      lipids (total cholesterol--TC, cholesterol LDL--LDL-C, cholesterol HDL--HDL-C, TG
      -by enzymatic method), membrane cholesterol in erythrocytes (method of IIcy), ET
      1 (immunoenzymatic method), fasting glucose level was (colorimetric method), uric
      acid (enzymatic--colorimetric method). RESULTS: After two months therapy of
      anthocyanins from Aronia melanocarpa in comparison with baseline it was observed
      a significant decrease of: SBP (144.20 +/- 9.97 vs. 131.83 +/- 12.24 mmHg, p <
      0.001) and DBP (87.20 +/- 9.9 vs. 82.13 +/- 10.33 mmHg, p < 0.05), TC (242.80 +/-
      34.48 vs. 227.96 +/- 33.07 mg/dl, p < 0.001), LDL-C (158.71 +/- 35.78 vs. 146.21
      +/- 34.63 mg/dl, p < 0.01), TG (215.92 +/- 63.61 vs. 187.58 +/- 90 mg/dl, p <
      0.05), ET-1 (2.44 +/- 0.51 vs. 1.74 +/- 0.42 pg/ml, p < 0.001) and membrane
      cholesterol (4.85 +/- 0.65 vs. 2.81 +/- 0.54 mmol/Lpc, p < 0.001), uric acid and
      fasting blood glucose levels did not change significantly after study cessation.
      CONCLUSIONS: The results of our study show that anthocyanins from Aronia
      melanocarpa may be of benefit to patients with MS as for as atherosclerosis
      prevention is concerned. It seems to result from anthocyanins influence on blood
      pressure, serum lipid and endothelin-1 level.

PMID- 18044342
TI  - [Concomitant myeloid sarcoma and plasma cell myeloma--case report of a hitherto
      undescribed association of two neoplasms].
AB  - A 65-year-old male patient initially presented with a penile tumour, identified
      as myeloid sarcoma. Subsequent bone marrow investigation revealed the presence of
      a synchronous plasma cell myeloma, without any evidence of a bone marrow-based
      myeloproliferative disorder. Although the course of both neoplasms was
      progressive, with increasing bone marrow involvement by the plasma cell myeloma
      and cutaneous dissemination of the myeloid sarcoma, both neoplasms remained
      confined to their original tissue compartments. Different biology of both
      tumours, including markedly divergent response to therapies, contributed to a
      significant clinical dilemma and finally to the patient demise 16 months after
      the presentation. While the association of plasma cell myeloma and various
      myeloid leukaemias is well documented, this is a first report of simultaneous
      occurrence of a myeloma and a myeloid sarcoma.

PMID- 18044343
TI  - [Melatonin in the treatment of atherosclerosis].
AB  - Atherosclerosis is currently concerned as a chronic inflammatory process, which
      is response to an endothelial damage. Therapy of atherosclerosis should influence
      on various mechanisms. Substances which can prevent and treat this disorder are
      still being investigated. Melatonin exerts anti-inflammatory and antioxidative
      properties, which implies that it can be useful in the treatment of
      atherosclerosis. Melatonin neutralizes ROS (reactive oxygen species), increases
      antioxidative enzymes activities and glutathione levels, prevents electron
      leakage from mitochondrial respiratory chain, acts synergistically with vitamins
      C, E, and glutathione. Melatonin reduces levels of proinflammatory cytokines: IL
      6, IL-12, TNF-alpha, IFN-gamma. In vivo studies and experiments on animals
      melatonin exerts beneficial effect on serum lipids, prevents LDL oxidation,
      decreases TBARS levels, increases total antioxidant capacity. However, some
      studies suggest that melatonin can exert atherogenic effects in animals. Clinical
      studies on patients who are in risk of atherosclerosis development are required.

PMID- 18044344
TI  - [The influence of melatonin on human reproduction].
AB  - This paper reviews the possible participation of melatonin in the process of
      human reproduction. The results of several studies have shown the clear
      correlation between melatonin and gonadotropins and/or sexual steroids, which
      suggest that melatonin may be involved in the sexual maturation, ovulation or
      menopause. Decreased secretion of melatonin which coexists with increased
      fertility in the summer is specific for women living on the north hemisphere.
      Moreover, abnormal levels of melatonin in the blood are associated with several
      disorders of the hypothalamus-pituitary-gonads axis activity, i.e., precocious or
      delayed pubertas, hypogonadotrophic or hypergonadotrophic hypogonadism or
      amenorrhoea. Melatonin binding sites have been demonstrated in the central
      nervous system (mainly in the pars dystalis of the pituitary and hypothalamic
      suprachiasmatic nucleus) as well as in the reproductive organs, e.g., human
      granulosa cells, prostate and spermatozoa. Melatonin can, therefore, influence
      the gonadal function indirectly--via its effect on gonadotropin-releasing hormone
      and/or gonadotropins secretion. It may also act directly; several data show that
      melatonin can be synthesized in gonads.

PMID- 18044345
TI  - [Reactive oxygen and nitrogen species in inflammatory process].
AB  - Reactive oxygen species (ROS) are generated in every cell during normal
      oxidation. The most important ROS include: superoxide anion (O2*-), hydroxyl
      radical (OH*), hydroperoxyl radical (HO2*), hydrogen peroxide (H2O2) and singlet
      oxygen ((1)O2*-). Reactive oxygen species can react with key cellular structures
      and molecules altering their biological function. Similarly reactive nitrogen
      species (RNS) such as nitric oxide (NO) or peroxinitrite anion (ONOO-) have
      physiological activity or reacts with different types of molecules to form toxic
      products. ROS and RNS are important in process of energy generation, lipids
      peroxidation, protein and DNA oxidation, nitration, nitrosation or nitrosylation
      and catecholamine response. Reactive oxygen/nitrogen species are neutralized by
      enzymatic activity or natural antioxidants that stop the initial formation of
      radicals. Overproduction of ROS or RNS results in "oxidative" or "nitrosative"
      stress which contributes to variety of pathological processes typical for
      different cancer, neurodegenerative, viral, toxic or inflammatory diseases.

PMID- 18044346
TI  - [CFQoL questionnaire as an assessment tool of quality of life in patients with
      cystic fibrosis].
AB  - The number of studies assessing quality of life, QOL, in patients with cystic
      fibrosis is quite small in world's and Polish literature, when compared with
      explosion of research concerning that topic in other disorders of the respiratory
      system. It is due to the fact that usage of general questionnaires or measures
      specific for other respiratory diseases turns out to be insufficient in the case
      of cystic fibrosis. Therefore, studies aimed at development and utilization of
      specific quality of life measures in cystic fibrosis are recommended. In this
      paper, quality of life measurement tools in cystic fibrosis and rules of their
      application are presented. Attention was paid to CFQoL, English questionnaire by
      Gee et al., which was validated as a quality of life measurement tool in cystic
      fibrosis (adults and adolescents). CFQoL, which Polish research proved to be a
      reliable tool as far as its psychometric parameters were concerned, was
      characterized here.

PMID- 18044347
TI  - [Immunopathology of Lyme arthritis].
AB  - Lyme borreliosis (Lyme disease) is the most prevalent tick-borne disease caused
      by spirochaetes of the Borrelia species complex. Arthritis is one of the common
      manifestations of B. burgdorferi infection. The pathomechanism of articular
      changes in Lyme arthritis has not yet been elucidated. Histopathological studies
      of synovia and immunological changes are similar to rheumatoid arthritis. In the
      early stage of inflammation B. burgdorferi interact with polynuclear granulocytes
      and epithelial cells, triggering production of reactive oxygen species, lipid
      peroxidation products and other inflammatory mediators. The imbalance between
      anabolic and catabolic processes in inflamed joints results in the progressive
      destruction of articular cartilage and disintegration of extracellular matrix.
      Molecular mimicry between OspA (outer surface protein A) and adhesion molecule
      LFA-1alpha seems to be responsible for chronic arthritis.

PMID- 18044348
TI  - [Parathyroid carcinoma].
AB  - Parathyroid carcinoma is a rare endocrine tumour accounting for only about one of
      every hundred cases of primary hyperparathyroidism. The aetiology of this cancer
      remains obscure but the recent studies have identified that some gene mutations
      may be involved in its pathogenesis. Most patients with parathyroid carcinoma
      suffer from symptoms related to marked hypercalcemia; the incidence of associated
      renal, bone, gastrointestinal, neuromuscular and psychological symptoms is much
      more frequent than in those with benign parathyroid adenomas. The course of
      patients with parathyroid carcinoma is variable. However, in more than 50% cases,
      patients experience persistent or recurrent disease due to regional or distant
      disease. The treatment of parathyroid malignancy is predominantly surgical,
      comprising an initial en bloc resection of the tumour and adjacent neck
      structures. Several studies have suggested the usefulness of pharmacotherapy in
      the palliative treatment of the debilitating symptoms of hypercalcemia. The aim
      of this paper is to summarise the present state of knowledge on the aetiology,
      clinical presentation, diagnosis and treatment of parathyroid carcinoma.

PMID- 18044349
TI  - [Problems connected with sexual activity in patients with heart disease].
AB  - The paper presents some basic data on sexual activity in patients with heart
      disease. The most typical problems of people with stable angina or after
      myocardial infarction connected with sexual intercourse have been presented.
      Modulation of risk of heart attack during sexual activity and main problems of
      sexual dysfunction after acute coronary syndromes have been described.

PMID- 18044350
TI  - [Developmental toxicity of naproxen].
AB  - Naproxen is a nonsteroidal antiinflammatory drug (NSAID) with an
      antiinflammatory, analgesic, antipyretic and tocolytic activity. Due to high
      therapeutical potency and good adult toxicological profile it is available as
      over-the-counter (OTC) drug. Experimental studies indicated that naproxen
      inhibited ovulation and readily passed the placental barrier. However, its
      developmental toxicity is not fully defined. Similar to other NSAIDs, naproxen
      causes constriction of the ductus arteriosus and fetal anuria or oliguria that
      could let to pulmonary arterial hypertension and oligohydramnion, respectively.
      It may also induce lip and/or palate clefts and cardiac malformations, especially
      the ventricular septal defect.

PMID- 18044351
TI  - [Changes in bones in the aging males].
AB  - The report contains a summary of results on bone changes in aging male, presented
      during the 2nd CSSAM/ISAM North American Congress on the Aging Male. It was shown
      that age-related osteoporosis can be slowed in men by substitutive treatment with
      testosterone. Taking into account such therapy, one should remember about its
      adverse effects.

PMID- 18044352
TI  - Sustainability--will it remain a dream?

PMID- 18044353
TI  - Wastewater disinfection alternatives: chlorine, ozone, peracetic acid, and UV
      light.
AB  - Disinfection tests were carried out at pilot scale to compare the disinfection
      efficiency of ozone, sodium hypochlorite (NaOCl), peracetic acid (PAA), and UV
      irradiation. Total coliforms, fecal coliforms, and Escherichia coli were
      monitored as reference microorganisms. Total heterotrophic bacteria (THB) were
      also enumerated by cytometry. At similar doses, NaOCl was more effective than
      PAA, and its action was less affected by contact time. The results obtained by
      ozonation were comparable for total coliforms, fecal coliforms, and E. coli. On
      the contrary, some differences among the three indicators were observed for
      NaOCl, PAA, and UV. Differences increased with increasing values of the
      disinfectant concentration times contact time (C x t) and were probably the
      result of different initial counts, as total coliforms include fecal coliforms,
      which include E. coli. The UV irradiation lead to complete E. coli removals, even
      at low doses (10 to 20 mJ/cm2). Total heterotrophic bacteria appeared to be too
      wide a group to be a good disinfection indicator; no correlation was found among
      THB inactivation, dose, and contact time.

PMID- 18044354
TI  - Biological solids reduction using the Cannibal process.
AB  - A laboratory study of the Cannibal process was undertaken to determine if the
      Cannibal system would generate less sludge compared with a conventional activated
      sludge system. Side-by-side sequencing batch reactors were operated--one using
      the Cannibal configuration and the other as conventional activated sludge. It was
      found that the Cannibal process generated 60% less solids than the conventional
      activated sludge system, without any negative effect on the effluent quality or
      the settling characteristics of the activated sludge. The oxygen uptake rate for
      the centrate from the Cannibal bioreactor showed that readily biodegradable
      organic matter was released from the recycled biomass in the Cannibal bioreactor.
      It is proposed that the mechanism for reduced solids from the Cannibal system is
      that, in the Cannibal bioreactor, iron is reduced, releasing iron-bound organic
      material into solution. When the Cannibal biomass is recirculated back to the
      aeration basin, the released organic material is rapidly degraded.

PMID- 18044355
TI  - The effect of wastewater treatment on antibiotic resistance in Escherichia coli
      and Enterococcus sp.
AB  - The effects of wastewater treatment on the proportion of Escherichia coli and
      Enterococcus sp. resistant to specific antibiotics were investigated at two
      facilities in Davis County, Utah, one of which received hospital waste. Samples
      were taken from the influent, effluent before disinfection, and secondary
      anaerobic sludge digester effluent. There was very little difference in
      antibiotic resistance among E. coli in the inflow waters of the plants but the
      plant receiving hospital waste had a significantly higher proportion of
      antibiotic resistant Enterococcus. The effect of wastewater treatment on
      antibiotic resistance was more pronounced on enterococci than E. coli. Although
      some increases in antibiotic resistance were observed, the general trend seemed
      to be a decrease in resistance, especially in the proportion of multidrug
      resistant Enterococcus sp.

PMID- 18044356
TI  - Synthesis of polyhydroxyalkanoates in municipal wastewater treatment.
AB  - Biologically derived polyesters known as polyhydroxyalkanoates (PHAs) represent a
      potentially "sustainable" replacement to fossil-fuel-based thermoplastics.
      However, current commercial practices that produce PHA with pure microbial
      cultures grown on renewable, but refined, feedstocks (i.e., glucose) under
      sterile conditions do not represent a sustainable commodity. Here, we report on
      PHA production with a mixed microbial consortium indigenous to an activated
      sludge process on carbon present in municipal wastewaters. Reactors operated
      under anaerobic/aerobic and aerobic-only mode and fed primary solids fermenter
      liquor maintained a mixed microbial consortium capable of synthesizing PHA at 10
      to 25% (w/w), while reducing soluble COD by approximately 62 to 71%. More
      critically, an aerobic batch reactor seeded from the anaerobic/aerobic reactor
      and fed fermenter liquor achieved approximately 53% PHA (w/w). Results presented
      suggest that environmentally benign production of biodegradable polymers is
      feasible. We further used PHA-rich biomass to produce a natural fiber-reinforced
      thermoplastic composite that can be used to offset advanced wastewater treatment
      costs.

PMID- 18044357
TI  - Nitrogen removal from urban stormwater runoff through layered bioretention
      columns.
AB  - Bioretention is a low-impact technology used for the treatment of stormwater
      runoff in developed areas. The fates of mineral nitrogen compounds in two
      bioretention columns (RP1 and RP2) with different media-layering characteristics
      were investigated under multiple loadings of simulated urban runoff. The
      immediate capture of nitrogen was evaluated, with nitrogen transformation
      reactions that occurred during the drying periods between rainfall events. A
      greater proportion of ammonium was removed from runoff in RP2 (68 +/- 16%), which
      had a high permeability layer over a lower permeability layer, than in RP1 (12 +/
      6%), which had the inverse configuration. Both column systems demonstrated
      nitrate export (9 +/- 32% and 54 +/- 22% greater than input for RP1 and RP2,
      respectively), attributed to washout of nitrate resulting from nitrification
      processes between runoff loading events. Bioretention media with a less permeable
      bottom soil layer could form an anoxic/anaerobic zone for promoting
      nitrification/denitrification processes.

PMID- 18044358
TI  - Effects of sludge properties on the thickening and dewatering of waste activated
      sludge.
AB  - The thickening and dewatering of waste activated sludge, from a pilot-scale
      submerged membrane bioreactor and two bench-scale, complete-mix activated sludge
      reactors (high-shear and low-shear aeration) treating the same municipal primary
      effluent, were investigated. Solids settling and compaction were measured using
      the diluted sludge volume index (DSVI) analysis and a batch centrifugation
      analysis, respectively. Elevated levels of filamentous microorganisms resulted in
      higher DSVI values and lower centrifuged pellet concentration. Elevated levels of
      nocardioform bacteria resulted in lower solids float concentrations, and higher
      colloidal material reduced solids recovery in batch flotation experiments. Sludge
      filterability, measured as time-to-filter, was shown to be a function of
      extracelluar polymeric substances and colloidal material, where higher levels of
      either reduced sludge filterability. Additional research is necessary to confirm
      these results using full- or demonstration-scale thickening and dewatering units.

PMID- 18044359
TI  - Enhanced removal of lead(II) and cadmium(II) from water in alum coagulation by
      ferrate(VI) pretreatment.
AB  - A laboratory study demonstrated that ferrate pretreatment significantly enhanced
      lead and cadmium removal in alum coagulation, under the conditions of natural
      surface water. The enhancement of lead removal was approximately 21 to 37% by
      ferrate pretreatment at a dosage of 1 to 5 mg/L. The enhanced removal of cadmium
      by ferrate pretreatment at a dosage of 1 to 5 mg/L exceeded the removal by alum
      coagulation alone 2-to 12-fold. Cadmium is much more difficult to remove than
      lead in alum coagulation. The performance of ferrate in enhancing the removal of
      lead and cadmium in alum coagulation was better than that of ferric chloride. The
      removal of lead and cadmium was highly pH-dependent, following the general trend
      of higher pH being related to higher removal. Satisfactory removal of cadmium
      could be expected by ferrate pretreatment combined with adjusting the pH of the
      water.

PMID- 18044360
TI  - Degradation of X-ray contrast media compounds by combined ozone and ultrasound.
AB  - The aqueous degradation of iodinated X-ray contrast media (ICM) by the
      combination of ozone and ultrasound has been studied. Experiments were conducted
      at a constant ultrasound frequency of 20 kHz, at five power densities up to 0.235
      W/mL, and various ozone centrations. In experiments involving dissolved ozone in
      solution, the addition of ultrasound significantly decreased the oxidation
      performance of the dissolved ozone, while the combination of dissolved oxygen and
      ultrasound gave a greater oxidation performance than ultrasound alone. However,
      the combination of gaseous ozone and ultrasound was found to give a higher degree
      of compound degradation than either ozone or ultrasound alone. In the experiments
      with final effluent, the degradation of ICM compounds by gaseous ozone and
      ultrasound was found to depend on the ozone dose applied. The degradation of ICM
      compounds in final effluent was modeled, which was found to moderately
      overestimate the observed compound degradation.

PMID- 18044361
TI  - Determination of growth rate and yield of nitrifying bacteria by measuring carbon
      dioxide uptake rate.
AB  - Nitrifier growth parameters--the maximum growth rate (microAmax) and yield (YA)-
      were estimated by measuring the rate of carbon dioxide uptake and additional
      rates of oxygen uptake and ammonia (or nitrite) use. Batch tests in a combined
      titrimetric and offgas analyzer with enriched Nitrobacter and Nitrosomonas
      cultures and an activated sludge sample were performed. The measured microAmax
      values for the Nitrobacter and Nitrosomonas cultures were 0.67 +/- 0.03 day(-1)
      and 0.54 +/- 0.09 day(-1), while the YA values were 0.072 +/- 0.01 g volatile
      suspended solids (VSS) x g nitrogen (N)(-1) and 0.14 +/- 0.02 gVSS x gN(-1),
      respectively. For the activated sludge sample, microAmax was observed to increase
      with pH (microAmax = 0.72 x 3.3(pH-7.1)) over the range 6.8 to 7.1. All microAmax
      and YA values determined by this method were similar to those previously
      reported. Compared with other microAmax and YA estimation methods, this method
      allows for unique microAmax and YA estimations for given conditions from a single
      experiment.

PMID- 18044362
TI  - Biodecolorization of the azo dye Reactive Red 2 by a halotolerant enrichment
      culture.
AB  - The decolorization of the azo dye Reactive Red 2 (RR2) under anoxic conditions
      was investigated using a mesophilic (35 degrees C) halotolerant enrichment
      culture capable of growth at 100 g/L sodium chloride (NaCl). Batch decolorization
      assays were conducted with the unacclimated halotolerant culture, and dye
      decolorization kinetics were determined as a function of the initial dye,
      biomass, carbon source, and an externally added oxidation-reduction mediator
      (anthraquinone-2,6-disulphonic acid) concentrations. The maximum biomass
      normalized RR2 decolorization rate by the halotolerant enrichment culture under
      batch, anoxic incubation conditions was 26.8 mg dye/mg VSSxd. Although RR2
      decolorization was inhibited at RR2 concentrations equal to and higher than 300
      mg/L, the halotolerant culture achieved a 156-fold higher RR2 decolorization rate
      compared with a previously reported, biomass-normalized RR2 decolorization rate
      by a mixed mesophilic (35 degrees C) methanogenic culture in the absence of NaCl.
      Decolorization kinetics at inhibitory RR2 levels were described based on the
      Haldane model (Haldane, 1965). Five repetitive dyeing/decolorization cycles
      performed using the halotolerant culture and the same RR2 dyebath solution
      demonstrated the feasibility of biological renovation and reuse of commercial
      strength spent reactive azo dyebaths.

PMID- 18044363
TI  - Screening for mercury in aqueous environmental samples and urine samples using
      thin layer chromatography.
AB  - A method for screening based on thin layer chromatography (TLC) comprising silica
      gel 'G' as a stationary phase and benzene as a mobile phase was found to be most
      suitable for the detection of mercury in aqueous samples and spiked human urine,
      without digesting the samples. A broad range for the detection of mercury, from
      20 microg/L (20 ppb) to 1000 mg/L (1000 ppm), was established, by optimizing the
      experimental conditions. In urine samples, mercury could be detected also, at
      levels as low as 50 microg/L (50 ppb) or above. Mercury was detected by
      complexation with dithizone followed by TLC, also in the presence of other heavy
      metals, including arsenic, cadmium, lead, copper, iron, zinc, and nickel. The
      method is simple, cheap, and has no interference of the matrix present in the
      natural water and aqueous industrial effluent samples obtained from the field.
      Further, no sophisticated instrument is needed for the detection of mercury.

PMID- 18044364
TI  - Winning the battle for accurate, updated surgeon preference lists.

PMID- 18044365
TI  - Implant makers make deal with prosecutors.

PMID- 18044366
TI  - Making the break from 5 x 7 pref cards.

PMID- 18044367
TI  - OR logistics: learning from FEDEX.

PMID- 18044368
TI  - VHA project improves OR processes.

PMID- 18044369
TI  - Knowing when to stop: DNR in the OR.

PMID- 18044370
TI  - Benchmarking GI endoscope data.

PMID- 18044371
TI  - Spine surgery migrates to outpatient setting.

PMID- 18044372
TI  - An advanced spine surgery center.

PMID- 18044373
TI  - Health illiteracy.

PMID- 18044374
TI  - Kudos for the new AHA endocarditis prevention guidelines.

PMID- 18044375
TI  - Possible connection periodontal bacteria has with systemic conditions.

PMID- 18044376
TI  - Curing the silent epidemic: caries management in the 21st century and beyond.
AB  - Caries is the most prevalent disease of children and is epidemic in some
      populations. A risk-based approach to managing caries targets those in greatest
      jeopardy for contracting the disease, as well as provides evidence-based
      decisions to treat current disease and control it in the future. This paper
      outlines key concepts necessary to effectively manage and reduce caries based on
      the most current science to date. Subsequent articles will outline a roadmap to
      success in curing dental caries.

PMID- 18044377
TI  - Caries risk assessment appropriate for the age 1 visit (infants and toddlers).
AB  - This article discusses caries management by risk assessment for children age 0-5.
      Risk assessment is the first step in a comprehensive protocol for infant oral
      care. The program includes opportunities to establish a "dental home" and provide
      guidance for improved health outcomes. Risk assessment forms, instructions for
      use, and guidance-related education points have been included. Collaboration
      among all health professionals regarding early and timely intervention to promote
      children's oral health and disease prevention is emphasized.

PMID- 18044378
TI  - Caries risk assessment in practice for age 6 through adult.
AB  - The aim of this article is to present a practical caries risk assessment
      procedure and form for patients who are age 6 through adult. The content of the
      form and the procedures have been validated by outcomes research after several
      years of experience using the factors and indicators that are included.

PMID- 18044379
TI  - Clinical protocols for caries management by risk assessment.
AB  - This article seeks to provide a practical, everyday clinical guide for managing
      dental caries based upon risk group assessment. It is based upon the best
      evidence at this time and can be used in planning effective caries management for
      any patient. In addition to a comprehensive restorative treatment plan, each
      patient should have a comprehensive caries management treatment plan. Some sample
      treatment plans are included.

PMID- 18044381
TI  - Dental Spa-ahhhhh.

PMID- 18044380
TI  - Products--old, new, and emerging.
AB  - The paradigm shift in understanding the etiology, prevention, and treatment of
      dental caries requires an understanding of the dental products that are currently
      available to assist the clinician in prudent recommendations for patient
      interventions. The purpose of this review is to present the evidence base for
      current products and those that have recently appeared on the market.

PMID- 18044382
TI  - The ICP: infection prevention and control practitioner or infection prevention
      and control professional?

PMID- 18044383
TI  - Single-use device reuse risks.
AB  - Efforts to reduce both costs and medical waste have led many health systems to
      start reusing single-use medical devices (SUDs) after cleaning and sterilizing
      (i.e. reprocessing). There is a currently a wide range of SUD types being reused
      in many health systems. The objective of this paper is to provide a brief summary
      of risk issues associated with critical SUDs, based on a rapid review of the
      available literature. The specific focus is on risk issues, but includes
      discussion of economic and legal/ethical issues as well. The evidence in the
      literature regarding the safety of reuse of SUDs indicates that for certain
      devices (e.g. heart catheters) reuse can be safe (in terms of patient infection)
      and cost-effective as long as stringent reprocessing protocols are followed.
      However, potential risks associated with reusing SUDs are not just limited to
      infection of patients. There are staff and environmental risks, plus important
      legal, ethical, and financial issues to consider in a reuse policy. There are
      currently no Canadian guidelines on reuse or reprocessing SUDs, although a
      national Scientific Advisory Panel on Reprocessing of Medical Devices has made
      recommendations. Additionally, reuse of SUDs is interwoven with the issue of
      infection control and reprocessing procedures in general and as applied to
      multiple-use devices. With limited healthcare resources, there will always be a
      trade-off between the human resources and costs required to clean and sterilize
      reused devices with costs associated with purchasing and disposing of non-reused
      SUDs. Evaluation of complete operational pathways, especially for more expensive
      and commonly used SUDs, will be useful to properly determine the balance of
      benefits, risks, and costs under a reuse policy.

PMID- 18044384
TI  - Acinetobacter baumannii in casualties returning from Afghanistan.
AB  - Military personnel returning from Afghanistan and entering Canadian hospitals may
      be infected with multidrug resistant Acinetobacter baumannii. The Public Health
      Agency of Canada, in conjunction with the Canadian Forces, have developed an
      alert to inform hospitals of the potential for importation of Acinetobacter
      baumannii, and the appropriate precautionary measures that should be taken to
      prevent secondary spread within hospitals.

PMID- 18044385
TI  - Paramedic services workplace program improves influenza immunization rates among
      paramedics.

PMID- 18044386
TI  - Identification badges: a potential fomite?
AB  - BACKGROUND: Staff identification badges are mandatory in all hospitals. The
      purpose of this study was to assess microbial contamination of identification
      badges at a Canadian tertiary centre. Risk factors for badge contamination were
      also investigated. METHODS: Badges were cultured from 118 subjects including
      secretaries, physicians, nurses, and allied health workers. Subjects also
      completed a demographic questionnaire. Badge contamination was analyzed according
      to profession, workplace, duration of badge use, presence of a plastic cover, how
      the badge was worn, and cleaning frequency. RESULTS: 13.6% of the badges were
      contaminated with significant pathogens. S. aureus was isolated in 6.8% of the
      badges, gram-negative bacilli in 5.9%. Contamination was highest in nurses (21.4%
      versus 9.4-14.3% in other professions) and in the ICU (22.6% versus 8.3%-14.3% at
      other locations). Neither association was statistically significant. Covered and
      non-covered badges had similar contamination rates (12% and 17.1%) as did badges
      worn around the neck compared with those worn clipped to clothing (13.0% versus
      14.6%). Contamination of recently cleaned badges was not statistically different
      from those that had not. CONCLUSION: Identification badges do not appear to be a
      major reservoir for pathogenic organisms. Badges can, however, harbour disease
      causing organisms and should be cleaned regularly.

PMID- 18044387
TI  - Drama: a venue for staff education.

PMID- 18044388
TI  - Interference. Worst part of the best job in the world.

PMID- 18044389
TI  - The power of polite. How something so simple can have a far-reaching impact.

PMID- 18044390
TI  - Overseas delivery. Severe symptoms signal possible danger on an arriving
      international flight.

PMID- 18044391
TI  - Situational syncope. Why people faint, and what to do about it.

PMID- 18044392
TI  - Managing a major incident. Essential elements of a successful outcome.

PMID- 18044393
TI  - Bug patrol. Basic principles of cleaning, decontamination and disinfection for
      EMS.

PMID- 18044394
TI  - NHTSA releases EMS pandemic influenza guidelines.

PMID- 18044395
TI  - Do you have an exposure control plan?

PMID- 18044396
TI  - Should we fear the pandemic? New technology may make quick work of pandemic
      influenza.

PMID- 18044397
TI  - Prehospital pharmacology: anti-emetics.
AB  - Although there is a paucity of literature on anti-emetic administration in the
      prehospital setting, paramedic delivery of an appropriate agent according to
      protocol can decrease the time to treatment for hundreds of thousands of
      emergency department patients annually who access 9-1-1 and present with nausea
      and vomiting.

PMID- 18044398
TI  - The meth lab menace. What responders should know about these dangerous
      environments.

PMID- 18044399
TI  - Beyond the basics: endocrine emergencies. Part 2: hypothyroidism and myxedema
      coma.

PMID- 18044400
TI  - Straight to the heart. By understanding the heart's anatomy, you can understand
      cardiac disorders and terminology.

PMID- 18044401
TI  - Smooth handoffs. How to put the team focus back into ALS/BLS interactions.

PMID- 18044402
TI  - [Pathogenesis of irritable bowel syndrome: current understanding].
AB  - Irritable bowel syndrome is one of the most frequent functional bowel disorders.
      The pathogenesis of the condition is not completely understood, but an alteration
      of the neural circuits that regulate the sensory-motor homeostatic reflex
      responses to visceral stimuli is involved. The causes of this alteration are
      unknown and include both genetic and environmental factors, such as a previous
      gastrointestinal infection. A more precise definition of the pathogenesis of the
      condition might help to develop more effective treatments to correct the altered
      sensitive and motor reflex responses in the patients.

PMID- 18044403
TI  - [Immigration and hepatitis B virus in Italy. Current state and perspectives].
AB  - This work underlines as many people arrive in our country by migratory phenomena
      and as many of them come by areas, particularly Sub-Sahara Africa, endemic for
      HBV infection. This could determine a higher prevalence of this infection in our
      area. The most part of subjects could be infected by a non-D genotype (genotype D
      is prevalent in Italy) characterized by a different natural history and response
      to antiviral therapies with the necessity of a different clinical and therapeutic
      approach.

PMID- 18044404
TI  - [Acute and prolonged infectious diarrheas, of microbial and viral etiology:
      methods of clinical and microbiological diagnosis].
AB  - The Authors relate clinical-microbiological criteria for a rational diagnosis of
      acute and prolonged enteritis, distinguishing between home and imported
      diarrheas. During 2005, 381 subjects (192 children and 189 adults) with acute
      diarrhea and 110 subjects (16 children and 94 adults) with prolonged diarrhea
      were examined. In the first group Salmonella prevailed in 11.1% of cases (10.9%
      among children and 11.1% among adults); Campylobacter in 9.2% (respectively 8.9%
      and 9.5%); other bacteria were identified in 3.2% of cases (1.0% and 3.8%
      respectively). Rotavirus were observed in 29.5% of children and Adenovirus in
      6.2% of pediatric population. Pathogenic protozoa were observed in 1.6% of people
      (0.5% in children and 2.7% in adults). Among second group pathogenic protozoa
      prevailed in 6.4% (6.3% in children and 6.4% in adults); toxin A of C. difficile
      were detected in 8.5% of total cases. The Authors emphasize the importance to
      investigate always for Salmonella, Shigella and Campylobacter; in children with
      vomiting (with acute non invasive enteritis) is necessary to investigate for
      Rotavirus too; if the diarrhea is prolonged could be important investigate for
      toxin A/B of C. difficile and for protozoa with specific stains. Based on
      clinical and epidemiological findings other pathogens could be researched, if
      possible for own resources.

PMID- 18044405
TI  - [Infliximab in moderate to severe steroid-dependent or steroid-refractory
      ulcerative colitis].
AB  - Tumor Necrosis Factor alpha plays a main role in ulcerative colitis. Thirteen
      male and 8 female affected by moderate to severe steroid-dependent or refractory
      severe ulcerative colitis were treated with 5 mg/kg of infliximab (Remicade). At
      12 week efficacy, steroid-sparing, colectomy and side effects were evaluated. In
      steroid-dependent group (13 patients): 8 patients had a clinical benefit (7
      obtained a clinical remission, 54%), 8 (61.5%) discontinued steroids, 1 patient
      underwent surgery. In steroid-severe refractory group (8 patients): 3 patients
      (37.5%) had a clinical remission, 2 (25%) had a clinical response and 3 (37.5%)
      underwent colectomy. One mild infusion reaction and one adverse event (itch) were
      observed. Infliximab is an effective and safe therapy in patients with moderate
      to severe steroid dependent and refractory ulcerative colitis.

PMID- 18044406
TI  - [Lipomatosis of interatrial septum and supraventricular arrhythmias].
AB  - Lipomatosis of interatrial septum is a rare benign disorder characterized by fat
      accumulation into interatrial septum. It may cause atrial arrhythmias and
      hemodynamic complications. For this reason, it should be considered in
      differential diagnosis of other cardiac masses. We report the typical case of
      lipomatosis of interatrial septum and atrial flutter.

PMID- 18044407
TI  - [Physicians working in internal medicine's ward: a survey on their role in the
      management of the gastrointestinal endoscopy services in Emilia Romagna].
AB  - We carried out a survey on the role played by the Wards of Internal Medicine in
      the management of the Gastrointestinal Endoscopy (G.E.) Services operating in
      Emilia Romagna. 45 G.E. Services were censored, for a total of 225 endoscopists:
      105 out of them (46.7%) were gastroenterologists and 84 (37.3%) were surgeons,
      whereas just 35 (15.6%) were working in Internal Medicine's Ward and 1 (0.4%) was
      working in a Division of Geriatrics. A significant difference was observed
      analyzing the composition of the G.E. staffs on the basis of the size and
      activity of G.E. Services (p < 0.001). Physicians working in Wards of Internal
      Medicine represented 9.2% and 24.5% of the endoscopists in the hospitals with or
      without a Gastroenterology Unit, respectively (p = 0.003). Based on these
      results, the physicians working in Internal Medicine's Ward seem to play a
      secondary role in G.E. Services. Their role is greater in small hospitals, but
      they are often compelled to operate under suboptimal circumstances.

PMID- 18044408
TI  - [Familial intrahepatic cholestasis. Novel advances].
AB  - In the last years hepatology has known remarkable improvement to understanding
      the mechanisms involved in familial intrahepatic cholestasis. The role of genetic
      anomalies is very important. Identification of genes involved in familial
      intrahepatic cholestasis has proven to be an important strategy to unravel the
      processes of bile acid synthesis and bile salt transport. The complexity of the
      mechanisms of bile flow clearly suggests that many more genetic abnormalities
      have yet to be identified.

PMID- 18044409
TI  - [Treatment for Helicobacter pylori: current criteria].
AB  - H. pylori eradication following standard triple therapies is decreasing
      worldwide, mainly due to an increased prevalence of bacterial resistance against
      antibiotics. Therefore, to cure such an infection remains a challenge for
      clinicians. This paper aimed to review the currently available therapeutic
      approaches, for which large and consistent data exist in literature, in order to
      update H. pylori management in the clinical practice. According to the updated
      European Guidelines, the first-line therapy should be chosen based on the
      prevalence of clarithromycin resistance. A 7-day triple therapy should be
      employed if clarithromycin resistance is lower than 15-20%, whilst this regimen
      should be prolonged to 14 days where resistance is higher. A 7-day quadruple
      therapy is suggested as second-line treatment. However, quadruple therapy is no
      more available in Italy. According to the forthcoming Italian Guidelines, a new
      "therapeutic package" could be used, including a 10-day sequential regimen as
      first-line therapy and a 10-day levofloxacin-based regimen as re-treatment. The
      sequential regimen (5-day dual plus 5-day triple therapy) achieved an eradication
      rate constantly >90% in several Italian studies, being more effective than
      standard triple therapy, even in patients with clarithromycin resistant strains.

PMID- 18044410
TI  - [Pathophysiology of cholangiocytes: recent advances].
AB  - A bulk of researches performed in the last decade highlighted the extraordinary
      biological properties of cholangiocytes involved in a number of important
      processes such as bile formation, proliferation, injury repair, fibrosis,
      angiogenesis and regulation of blood flow. Cholangiocytes proliferation is a key
      mechanism capable of conditioning the evolution of liver damage. Proliferating
      cholangiocytes, in fact, acquire the phenotype of neuroendocrine cells and
      secrete different substances which represent the tools of cross-talk with other
      hepatic cells. Recent advances on the molecular and cell biology of
      cholangiocytes are opening new potential therapeutic perspectives for the human
      chronic liver diseases.

PMID- 18044411
TI  - Upright and whole: an approach to suffering in the face of death.

PMID- 18044412
TI  - Unexpectedly high prevalence of akathisia in cancer patients.
AB  - OBJECTIVES: Complications of neuropsychiatric disorders are often detected in
      cancer patients. Adjustment disorders, depression, or delirium are common
      psychiatric disorders in these patients, and drug-induced neuropsychiatric
      problems are sometimes referred for psychiatric consultation. Prochlorperazine
      and other antiemetic drugs that are phenothiazine derivates are also reported to
      cause akathisia due to the blockade of the dopamine receptor in the central
      nervous system, but the, prevalence of akathisia in patients undergoing cancer
      treatment has not been reported. This study seeks to explore the prevalence of
      such drug-induced syndromes (e.g., akathisia) in this population. METHODS: This
      present study was a prospective study. The subjects of this study were 483
      consecutive patients with cancer who had been referred to the Department of
      Psychiatry in Kanagawa Prefecture Cancer Center from February 1, 2004, to
      November 30, 2005. Trained psychiatrists conducted a nonstructured psychiatric
      interview and neurologic examination to establish psychiatric diagnoses according
      to DSM-IV and the presence or absence of drug-induced extra pyramidal symptoms.
      The past and current medications used in their cancer treatment were also
      examined in detail for an accurate evaluation. RESULTS: A psychiatric diagnosis
      was made in 420 (87.0%) of the 483 cancer patients examined, and akathisia, a
      drug-induced movement disorder, was unexpectedly prevalent among the patients; 20
      of 420 (4.8%) patients had developed akathisia from an antiemetic drug,
      prochlorperazine. SIGNIFICANCE OF RESULTS: Diagnosing such adverse drug reactions
      may be difficult due to complicating factors in cancer treatment, and the inner
      restlessness observed in akathisia is likely to be regarded as a symptom of a
      primary psychiatric disorder. The authors suggest that oncologists should
      optimize the use of antiemetic drugs and be aware of akathisia as a possible
      complication of cancer treatment.

PMID- 18044414
TI  - Facing uncertainty: the lived experience of palliative care.
AB  - OBJECTIVE: This qualitative research study listens to the narratives of people
      experiencing the dying process who attended the Otago Community Hospice, Dunedin,
      New Zealand. METHODS: Ten people, aged between 51 and 65, were approached; two
      declined and one died sooner than expected. All were women (although this was not
      part of the original design) and all had carcinoma. Data for the study was sought
      through qualitative research interviews, considering the development of each
      participant's illness in relation to her perception of her embodiment in the
      palliative care setting, and concluding with questions about what she wants the
      people who care for and about her to learn from her experience. Consistent with
      this phenomenological approach, the method of analysis was thematic and
      interpretive. RESULTS: The main theme was the uncertainty that all participants
      felt throughout the diagnostic process and during treatment. Uncertainty, too,
      was a factor in how they managed their day, whether they would be able to sustain
      an outing or an activity or not and whether they would be pain free. None were
      afraid of dying but hoped that when they did die, they would do so comfortably.
      The relationship with their general practitioners varied. Where fatigue or the
      effects of medication were not an issue, they could think clearly, but their
      bodies were experienced as letting them down and limiting their activities. The
      ideal of "living until you die" was not able to be fulfilled. The increasing
      approach of social death as they withdrew from their employment and social
      responsibilities affected them. SIGNIFICANCE OF RESULTS: Whether one has a "good
      death" or not is determined not only by the progression and management of the
      disease process by health professionals, but also by the way in which one is
      perceived, by self and others. There are no guidelines for the dying role;
      everybody dies differently and individually.

PMID- 18044413
TI  - Parent and child perspectives on physician communication in pediatric palliative
      care.
AB  - OBJECTIVE: Despite growing recognition of the importance of communication with
      children with life-limiting illnesses and their families, there has been limited
      research that includes the child's perspective. The purpose of the current study
      was to identify the aspects of physician communication that children with life
      limiting illnesses and their parents perceived to be facilitative or obstructive
      in pediatric palliative care. METHODS: This qualitative study reports on the
      first 20 parent and child pairs of pediatric oncology and cardiology patients
      (mean age 14.25 years, range 9-21 years) with a poor prognosis (physician
      reported likely < 20% chance of survival beyond 3 years) from two children's
      hospitals and one pediatric hospice in Los Angeles, California. Perspectives on
      physician communication were elicited from children's and parents' individual
      narratives, recorded, coded, and analyzed using qualitative grounded theory
      methodology. RESULTS: Both children and parents identified five domains of
      physician communication deemed to be highly salient and influential in quality of
      care. These included relationship building, demonstration of effort and
      competence, information exchange, availability, and appropriate level of child
      and parent involvement. Parents identified coordination of care as another
      important communication domain. The characteristics of physicians that were
      deemed most harmful to satisfying communication included having a disrespectful
      or arrogant attitude, not establishing a relationship with the family, breaking
      bad news in an insensitive manner, withholding information from parents and
      losing their trust, and changing a treatment course without preparing the patient
      and family. SIGNIFICANCE OF RESULTS: The six positive communication domains are
      areas for clinicians to recognize and monitor in communicating with children and
      families in the pediatric palliative care setting. Knowledge of the qualities of
      communication that are satisfying to and valued by children and their parents
      have the potential to lead to more effective communication around the difficult
      decisions faced by physicians, parents, and children with life-threatening
      conditions.

PMID- 18044415
TI  - To what extent does meaning mediate adaptation to cancer? The relationship
      between physical suffering, meaning in life, and connection to others in
      adjustment to cancer.
AB  - OBJECTIVES: This study builds on previous work that explored the lived experience
      of meaning in advanced cancer. The aims were to explore the associations of
      suffering (physical and existential distress) and coping (via social support)
      with psychological distress and global meaning using a battery of instruments
      among adults attending an Australian metropolitan cancer service (n=100).
      METHODS: The contribution of suffering and coping via social support to
      psychological distress and meaning were examined using a variety of statistical
      methods. Multiple regression analyses were conducted to further examine relative
      contributions to both psychological distress and global meaning. RESULTS:
      Physical and existential distress were found to be positively associated with
      psychological distress whereas high social support and personal meaning are
      related to lower levels of psychological distress. Social support was the
      strongest correlate of global meaning whereas high levels of existential distress
      were related to lower levels of global meaning. On the basis of this study, it is
      concluded that the factors related to suffering clearly promote psychological
      distress, and the reverse is true for global meaning for those living with
      cancer. SIGNIFICANCE OF RESULTS: This study speaks to the clinical complexity of
      the dynamic experience of suffering and meaning in cancer. We need to better
      understand the impact of physical suffering and meaning in the lives of this
      population and to actively work toward the enhancement of social support and
      connection with others for this group. Optimal palliative and family-centered
      care blended with therapies that promote a sense of meaning of life lived appear
      crucial to ameliorate suffering.

PMID- 18044416
TI  - Family caregiver's experiences in caring for a patient with terminal cancer at
      home in Japan.
AB  - OBJECTIVES: The aim of the study was to clarify the care experience of primary
      caregivers when caring for a terminal cancer patient in the home with the
      assistance of a home palliative care service. Participants were asked to provide
      background data and to evaluate their experience of caregiving and of the
      patient's response throughout the period of home palliative care, up to the time
      of death. METHODS: One hundred twelve primary family caregivers were a mailed
      self-report questionnaire, and 74 valid questionnaires were returned (response
      rate 66%). RESULTS: Ninety percent felt that the patient's condition of mind and
      body was reasonably stable, and 75% felt that the death was peaceful. About 90%
      reported a deepening of their bond with the patient and that the bond of other
      family members deepened also. Sixty percent reported that the burden of
      caregiving was not too great or not felt at all. Approximately 90% judged that
      the patient retained his or her own personal qualities to the end. Ninety percent
      also felt that they had done their best in their caregiving and judged that home
      care had been beneficial for the deceased, for the primary caregiver him/herself,
      and for other family members. These primary caregivers' evaluations of caring for
      a terminally ill patient at home in conjunction with a home palliative care
      service were both high and positive. SIGNIFICANCE OF RESULTS: Our findings
      suggest that it is important to maintain the patient's personal qualities up to
      the time of death through appropriate symptom management, to respect the family
      bond of the household, and to provide professional support in order to reduce the
      load on the family. If appropriate care is provided, peaceful home death will be
      possible, resulting in significant benefits for patients and their families in
      Japan.

PMID- 18044417
TI  - Bereaved spouses' adjustment after the patients' death in palliative care.
AB  - OBJECTIVES: To improve the support to bereaved spouses during the year after the
      patient's death, a project was started consisting of three visits by a nurse
      (after 1, 3, and 13 months) with conversations about the patient's death and the
      spouse's life situation. The aim of this study was to describe the bereaved
      spouse's situation and adaptation during the first year after the loss. METHODS:
      Spouses of patients cared for by The Advanced Home Care Team (APHCT) in Uppsala,
      Sweden, were invited to participate in the project. Each participant was
      encouraged to talk freely about his or her situation, but enough direction was
      given to ensure that all items listed on a standardized questionnaire were
      covered. RESULTS: Fifty-one spouses met the inclusion criteria and were invited
      to participate and 45 accepted. The subjects felt quite healthy but were tired
      and suffered from sleep disturbance. The grief reactions had initially been high
      but showed a significant decline from 1 to 13 months (p < .01). Forty-nine
      percent had experienced postbereavement hallucinations. SIGNIFICANCE OF RESULTS:
      This study showed that the bereaved spouses felt quite healthy and adjusted quite
      well to their new life situation, after the patient's death in a palliative care
      setting. The grief reactions had initially been high but showed a significant
      decline during the year.

PMID- 18044418
TI  - Determinants of trust in the patient-oncologist relationship.
AB  - OBJECTIVE: The relationship between the patient and physician is at the heart of
      good medical care, and trust is an essential component of this relationship. To
      enable the oncologist to better form a trusting relationship with the patient,
      this article describes four factors that influence patient trust. METHODS:
      Thematic literature review and a clinical vignette. RESULTS: The authors discuss
      four factors that influence patient trust. These factors are whether and how the
      oncologist (1) minimizes the potential for shame and humiliation during the
      medical encounter, (2) manages the power imbalance between doctor and patient
      without abuse or misuse, (3) demonstrates to the patient an appreciation of how
      he or she is suffering from experience of cancer, and (4) demonstrates to the
      patient how he or she is suffering from the treatment provided by the oncologist.
      The authors illustrate these factors with a clinical vignette. SIGNIFICANCE OF
      RESULTS: The cancer patient is best cared for by an oncologist who can not only
      understand disease and treat medical problems, but also accompany the patient
      through the illness experience. This requires an appreciation of the challenges
      to trust that are inherent in the special characteristics of the patient
      physician interaction.

PMID- 18044419
TI  - Detection and treatment of akathisia in advanced cancer patients during adjuvant
      analgesic therapy with tricyclic antidepressants: case reports and review of the
      literature.
AB  - OBJECTIVE: There is substantial evidence that tricyclic antidepressants are
      effective in the management of chronic pain, including cancer pain. In
      oncological settings, these agents are used as adjuvant analgesic drugs. However,
      cases of akathisia due to tricyclic antidepressants used as adjuvant analgesic
      therapy have not previously been reported. CASE REPORTS: Two cancer patients
      experiencing chronic pain who were refractory to nonsteroidal anti-inflammatory
      drugs and opioids were prescribed amoxapine as an adjuvant analgesic therapy for
      neuropathic pain. These patients developed inner restlessness and restless
      physical movements after amoxapine was prescribed. Although symptoms were
      atypical, akathisia was suspected and discontinuation of amoxapine resolved the
      symptoms. RESULTS AND SIGNIFICANCE OF RESULTS: Akathisia should be considered in
      patients receiving adjuvant analgesic therapy with tricyclic antidepressants.
      Early detection and appropriate treatment will relieve this distressing symptom.
      Restless movements involving parts of the body other than the legs may be the
      clue to the diagnosis.

PMID- 18044420
TI  - Reflections on leukemia and adult stem-cell transplantation: some personal
      psychological factors.

PMID- 18044421
TI  - Microflora assessments using PCR-denaturing gradient gel electrophoresis of ozone
      treated and modified-atmosphere-packaged farmed cod fillets.
AB  - Denaturing gradient gel electrophoresis (DGGE) of a PCR-amplified 16S rDNA
      sequence was used to characterize changes in the microbial flora caused by ozone
      (O3) treatment of farmed cod (Gadus morhua). Portions of cod were produced under
      controlled conditions, bathed in fresh water supplemented with 2 ppm of O3 for 30
      min, and packaged in modified atmosphere (MA: 60% CO2 and 40% N2) before 4
      degrees C storage. Control samples were packaged in MA or air, without prior O3
      treatment. Samples were analyzed by PCR-DGGE to determine the predominant
      bacterial flora and to examine possible differences in the microbial community
      due to O3 treatment. The DGGE analysis during the storage period showed that the
      O3 treatment produced no significant difference in the microbial flora compared
      with the controls. Sequencing of 16S rDNA detected the specific spoilage bacteria
      Photobacterium phosphoreum, Pseudomonas spp., Shewanella baltica, and Shewanella
      putrefaciens as the predominant bacteria in all samples. PCR-DGGE results were
      supported by culture and sensory analyses used in predicting product shelf life.
      Aerobic plate count, H2S-producing bacteria, and psychrotrophic bacterial counts
      demonstrated no significant extension of the shelf life of MA-packaged, O3
      treated cod fillets.

PMID- 18044422
TI  - Prevalence and antimicrobial resistance of Salmonella recovered from processed
      poultry.
AB  - This study was conducted to determine the prevalence and antimicrobial resistance
      of Salmonella isolates recovered from processed poultry. Four hundred eighty pre-
      and postchill whole broiler chicken carcasses were collected from a poultry
      processing plant between July 2004 and June 2005. Water samples also were
      collected at the entrance and exit of the chiller. After preenrichment, carcass
      and water samples were analyzed for the presence of Salmonella using the
      automated BAX system followed by traditional culture methods. The proportions of
      pre- and postchill carcasses that were positive for Salmonella were 88.4 and
      84.1%, respectively. Ninety-two percent of water samples collected at the
      entrance of the chiller were positive for Salmonella, but all exit samples were
      negative. There was no significant difference in the prevalence of Salmonella
      between pre- and postchill carcasses (P > 0.05). Salmonella isolates recovered
      were serotyped and tested for susceptibility to antimicrobials. Thirteen
      serotypes were identified; the most common were Salmonella Kentucky (59.5%) and
      Salmonella Typhimurium (17.8%). Three hundred thirty-nine (79.8%) of the isolates
      were resistant to at least one antimicrobial, and 53.4% were resistant to three
      or more antimicrobials. Resistance was most often observed to tetracycline (73.4%
      of isolates), ampicillin (52.9%), amoxicillin-clavulanic acid (52%), ceftiofur
      (51.7%), streptomycin (35.2%), and sulfisoxazole (21.8%). These results indicate
      the high prevalence of Salmonella contamination in whole broiler carcasses, and a
      large number of these Salmonella isolates were resistant to commonly used
      antimicrobials.

PMID- 18044423
TI  - Attachment and biofilm formation by various serotypes of Salmonella as influenced
      by cellulose production and thin aggregative fimbriae biosynthesis.
AB  - This study was undertaken to quantify thin aggregative fimbriae and cellulose
      produced by Salmonella and to evaluate their roles in attachment and biofilm
      formation on polystyrene and glass surfaces. Thin aggregative fimbriae and
      cellulose produced by four wild-type and two pairs of Salmonella, representing
      four different colony morphotypes (rdar: red, dry, and rough; pdar: pink, dry,
      and rough; bdar: brown, dry, and rough; and saw: smooth and white), were
      quantified. The ability of the Salmonella cells to attach and form biofilms on
      the selected surfaces was evaluated in Luria-Bertani (LB) broth with or without
      salt (0.5%) or glucose (2%) at 28 degrees C during a 7-day period. The cells
      expressing the rdar or pdar colony morphotypes produced significantly greater
      amounts of thin aggregative fimbriae and cellulose on LB no salt agar,
      respectively. The cells expressing the rdar colony morphotype attached in higher
      numbers and formed more biofilm than did the cells expressing the pdar colony
      morphotype. The members of the pairs expressing the bdar colony morphotype
      attached more efficiently and formed more biofilm on the tested surfaces than did
      their counterparts expressing the saw colony morphotype. These results indicated
      that thin aggregative fimbriae impart attachment ability to Salmonella and, upon
      coexpression with cellulose, enhance biofilm formation on certain abiotic
      surfaces. The knowledge acquired in the study may help develop better cleaning
      strategies for food processing equipment.

PMID- 18044424
TI  - Effect of biofilm dryness on the transfer of Listeria monocytogenes biofilms
      grown on stainless steel to bologna and hard salami.
AB  - Listeria monocytogenes continues to be a major cause of class I food recalls in
      the United States. Very little is known about its transfer and cross
      contamination in processing scenarios. The objective of this study was to
      evaluate the effect of hydration level on L. monocytogenes biofilms grown on
      stainless steel and its effect on the biofilm transfer to foods. Biofilms were
      grown on stainless steel in diluted tryptic soy broth 1:20 for 48 h at 32 degrees
      C. After this, biofilms were equilibrated over saturated salt solutions at 20
      degrees C for 24 h (94, 75, 58, and 33% relative humidity; % RH) prior to
      transferring. Transfer experiments were conducted from inoculated stainless steel
      to bologna and hard salami at a constant pressure (45 kPa) and time (30 s) with a
      universal testing machine. The experiment was designed with a factorial design 4
      x 2 (biofilms equilibrated at 4% RH and two foods) and duplicated every day, and
      the whole experiment was repeated nine times. The results were analyzed with an
      analysis of variance by SAS Statistical Analysis Software. Our results showed
      that more bacteria were transferred to bologna (mean efficiency of transfer [EOT]
      = 3.0) than to hard salami (mean EOT = 0.35, P < 0.01). As biofilms became drier,
      the transfer of Listeria from stainless steel to both foods increased (P < 0.05).
      The EOT increased from 2 to 3.8 and from 0.2 to 0.51 upon transfer when drying
      the biofilm for bologna and hard salami, respectively. This study may be an
      indication that as biofilms were dried, the cell-cell and cell-surface
      interactions became weaker, and bacterial transfer increased. This phenomenon was
      enhanced in foods containing higher water activity levels. We hypothesize that
      this increased in transfer was due to the presence of capillary forces in the
      food.

PMID- 18044425
TI  - Modeling and predicting the growth of lactic acid bacteria in lightly preserved
      seafood and their inhibiting effect on Listeria monocytogenes.
AB  - A cardinal parameter model was developed to predict the effect of diacetate,
      lactate, CO2, smoke components (phenol), pH, NaCl, temperature, and the
      interactions between all parameters on the growth of lactic acid bacteria (LAB)
      in lightly preserved seafood. A product-oriented approach based on careful
      chemical characterization and growth of bacteria in ready-to-eat seafoods was
      used to develop this new LAB growth model. Initially, cardinal parameter values
      for the inhibiting effect of diacetate, lactate, CO2, pH, and NaCl-water activity
      were determined experimentally for a mixture of LAB isolates or were obtained
      from the literature. Next, these values and a cardinal parameter model were used
      to model the effect of temperature (T(min)) and smoke components (P(max)). The
      cardinal parameter model was fitted to data for growth of LAB (mu(max) values) in
      lightly preserved seafood including cold-smoked and marinated products with
      different concentrations of naturally occurring and added organic acids. Separate
      product validation studies of the LAB model resulted in average bias and accuracy
      factor values of 1.2 and 1.5, respectively, for growth of LAB (mu(max) values) in
      lightly preserved seafood. Interaction between LAB and Listeria monocytogenes was
      predicted by combining the developed LAB model and an existing growth and growth
      boundary model for the pathogen (O. Mejlholm and P. Dalgaard, J. Food Prot. 70:70
      84). The performance of the existing L. monocytogenes model was improved by
      taking into account the effect of microbial interaction with LAB. The observed
      and predicted maximum population densities of L. monocytogenes in inoculated
      lightly preserved seafoods were 4.7 and 4.1 log CFU g(-1), respectively, whereas
      for naturally contaminated vacuum-packed cold-smoked salmon the corresponding
      values were 0.7 and 0.6 log CFU g(-1) when a relative lag time of 4.5 was used
      for the pathogen.

PMID- 18044426
TI  - Inhibition of Listeria monocytogenes in cooked ham through active packaging with
      natural antimicrobials and high-pressure processing.
AB  - Enterocins A and B and sakacin K at 200 and 2,000 activity units (AU)/cm2, nisin
      at 200 AU/cm2, 1.8% potassium lactate, and a combination of 200 AU/cm2 of nisin
      and 1.8% lactate were incorporated into interleavers, and their effectiveness
      against Listeria monocytogenes spiked in sliced, cooked ham was evaluated.
      Antimicrobial-packaged cooked ham was then subjected to high-pressure processing
      (HPP) at 400 MPa. In nonpressurized samples, nisin plus lactate-containing
      interleavers were the most effective, inhibiting L. monocytogenes growth for 30
      days at 6 degrees C, with counts that were 1.9 log CFU/g lower than in the
      control after 3 months. In the other antimicrobial-containing interleavers, L.
      monocytogenes did not exhibit a lag phase and progressively grew to levels of
      about 8 log CFU/g. HPP of actively packaged ham slices reduced Listeria
      populations about 4 log CFU/g in all batches containing bacteriocins (i.e.,
      nisin, sakacin, and enterocins). At the end of storage, L. monocytogenes levels
      in the bacteriocin-containing batches were the lowest, with counts below 1.51 log
      CFU/g. In contrast, HPP moderately reduced L. monocytogenes counts in the control
      and lactate batches, with populations gradually increasing to about 6.5 log CFU/g
      at the end of storage.

PMID- 18044427
TI  - Effect of combining nisin and/or lysozyme with in-package pasteurization on
      thermal inactivation of Listeria monocytogenes in ready-to-eat turkey bologna.
AB  - Achieving a targeted lethality with minimum exposure to heat and preservation of
      product quality during pasteurization is a challenge. The objective of this study
      was to evaluate the effect of nisin and/or lysozyme in combination with in
      package pasteurization of a ready-to-eat low-fat turkey bologna on the
      inactivation of Listeria monocytogenes. Sterile bologna samples were initially
      treated with solutions of nisin (2 mg/ml = 5,000 AU/ml = 31.25 AU/cm2), lysozyme
      (10 mg/ml = 80 AU/ml = 0.5 AU/cm2), and a mixture of nisin and lysozyme (2 mg/ml
      nisin + 10 mg/ml lysozyme = 31.75 AU/cm2). Bologna surfaces were uniformly
      inoculated with a Listeria suspension resulting in a population of approximately
      0.5 log CFU/cm2. Samples were vacuum packaged and subjected to heat treatment
      (60, 62.5, or 65 degrees C). Two nonlinear models (Weibull and log logistic) were
      used to analyze the data. From the model parameters, the time needed to achieve a
      4-log reduction was calculated. The nisin-lysozyme combination and nisin
      treatments were effective in reducing the time required for 4-log reductions at
      62.5 and 65 degrees C but not at 60 degrees C. At 62.5 degrees C, nisin-lysozyme
      treated samples required 23% less time than did the control sample to achieve a 4
      log reduction and 31% less time at 65 degrees C. Lysozyme alone did not enhance
      antilisterial activity with heat. Results from this study can be useful to the
      industry for developing an efficient intervention strategy against contamination
      of ready-to-eat meat products by L. monocytogenes.

PMID- 18044429
TI  - Inactivation kinetics and factors of variability in the pulsed light treatment of
      Listeria innocua cells.
AB  - Pulsed light (PL) treatment can effectively reduce microbial populations in clear
      substrates and on surfaces, but its effectiveness varies as a function of
      substrate or treatment-related factors. For PL to be successfully adopted by the
      food industry, all factors of influence, as well as the inactivation kinetics for
      the microorganisms of concern, must be elucidated. In this study, the
      inactivation kinetics of Listeria innocua and the effect of inoculum size on PL
      inactivation were investigated. Stainless steel coupons (50.8 by 101.6 mm) of
      defined surface properties and transparent glass chamber slides (25.4 by 50.8 by
      10 mm) were each inoculated with 1 ml of aqueous suspensions of L. innocua
      containing inoculum populations of up to 10(9) CFU. The thickness of the liquid
      layer in the glass slides was 1.16 mm. The inoculated substrates were exposed to
      PL treatment of up to 17 J/cm2 in a static PL chamber equipped with a pulsed
      Xenon lamp. Survivors were recovered and enumerated by both standard plate
      counting and most-probable-number procedures. The data indicated that in clear
      liquids, PL resulted in more than a 6-log reduction of L. innocua after a 12
      J/cm2 treatment, regardless of the initial inoculum size. For the stainless steel
      surfaces, less than a 4-log reduction after a 12-J/cm2 treatment and a noticeable
      effect of substrate characteristics and inoculum size on inactivation were
      observed. The survivor curves showed pronounced tailing for all substrates used
      in the study. The Weibull model accurately predicted the survivor ratios for the
      PL treatment of L. innocua in clear liquids, with a shape and scale parameter of
      0.33 and 3.01, respectively. The Weibull model resulted in significant
      overestimation of PL effectiveness for the stainless steel substrates, where the
      influence of various substrate properties and inoculum level on inactivation was
      significant.

PMID- 18044428
TI  - A food-grade system for production of pediocin PA-1 in nisin-producing and non
      nisin-producing Lactococcus lactis strains: application to inhibit Listeria
      growth in a cheese model system.
AB  - Food-grade heterologous production of pediocin PA-1 in nisin-producing and non
      nisin-producing Lactococcus lactis strains, previously selected because of their
      technological properties for cheese making, was achieved. Plasmid pGA1, which
      contains the complete pediocin operon under the control of the strong P32
      promoter and is devoid of any antibiotic marker, was introduced into L. lactis
      ESI 153 and L. lactis ESI 515 (Nis+). Transformation of L. lactis ESI 515 with
      pGA1 did not affect its ability to produce nisin. The antimicrobial activity of
      the pediocin-producing transformants on the survival of Listeria innocua SA1
      during cheese ripening was also investigated. Cheeses were manufactured from milk
      inoculated with 1% of the lactic culture and with or without approximately 4 log
      CFU/ml of the Listeria strain. L. lactis ESI 153, L. lactis ESI 515, and their
      transformants (L. lactis GA1 and GA2, respectively) were used as starter
      cultures. At the end of the ripening period, counts of L. innocua in cheeses made
      with the bacteriocin-producing lactococcal strains were below 50 CFU/g in the L.
      lactis GA1 cheeses and below 25 CFU/g in the L. lactis GA2 ones, compared with
      3.7 million CFU/g for the controls without nisin or pediocin production.

PMID- 18044430
TI  - Relative efficacy of sodium hypochlorite wash versus irradiation to inactivate
      Escherichia coli O157:H7 internalized in leaves of Romaine lettuce and baby
      spinach.
AB  - Pathogenic bacteria that become internalized in leaf tissues are protected from
      the antimicrobial effects of surface treatments. Ionizing radiation is known to
      penetrate food tissues, but the efficacy of the process against internalized
      bacteria is unknown. Leaves of Romaine lettuce and baby spinach were cut into
      pieces, submerged in a cocktail mixture of three isolates of Escherichia coli
      O157:H7, and subjected to a vacuum perfusion process to force the bacterial cells
      into the intercellular spaces in the leaves. Scanning electron microscopy was
      used to evaluate the efficacy of the perfusion process. The inoculated leaves
      were then treated with a 3-min water wash, a 3-min wash with a sodium
      hypochlorite sanitizing solution (300 or 600 ppm), or various doses of ionizing
      radiation (0.25 to 1.5 kGy). Leaves were stomached to recover the internalized
      pathogen cells, which were enumerated. The vacuum perfusion effectively forced
      bacteria into the leaf vasculature and apoplast, as confirmed by scanning
      electron microscopy. For spinach leaf pieces, neither the water nor the sodium
      hypochlorite washes resulted in significant reductions of E. coli O157:H7 cells
      relative to the untreated control. For Romaine lettuce leaf pieces, 300 and 600
      ppm sodium hypochlorite each resulted in less than 1-log reduction; water wash
      was ineffective. Ionizing radiation, in contrast, significantly reduced the
      pathogen population, with 4-log (Romaine lettuce) or 3-log (spinach) reductions
      at the highest dose tested. In Romaine leaves, the reduction was dose dependent
      across the range of doses tested, with a D10-value (the amount of irradiation
      necessary to reduce the population by 1 log unit) of 0.39 kGy. In spinach leaves,
      the pathogen had a biphasic response, with a D10-value of 0.27 kGy in the range
      of 0 to 0.75 kGy but only slight additional reductions from 0.75 to 1.5 kGy. In
      this study, ionizing radiation but not chemical sanitizers effectively reduced
      viable E. coli O157:H7 cells internalized in leafy green vegetables, but the
      response of the pathogen to irradiation was more complex in spinach leaves than
      in Romaine lettuce leaves.

PMID- 18044431
TI  - Modeling of the effect of washing solution flow conditions on Escherichia coli
      O157:H7 population reduction on fruit surfaces.
AB  - Washing produce with sanitizing solutions is an important step in reducing
      microbial populations during postharvest handling. Little information exists
      regarding the effects of washing solution flow conditions on the efficacy of
      pathogen reduction during washing. This study was undertaken to investigate the
      effects of washing conditions such as flow velocity, agitation rate, and contact
      time on the reduction of Escherichia coli O157:H7 populations from the surfaces
      of cantaloupe rind and cut apples. Top surfaces of cylindrical samples were spot
      inoculated with E. coli O157:H7 and treated with peroxyacetic acid (POAA; 80
      mg/liter) solution under different flow velocities and agitation rates and with
      different washing modes. Test results indicate that the reduction rate of E. coli
      O157:H7 increased with the increase in flow velocity and agitation rate under the
      testing conditions. In a 3-min treatment in the flow-through chamber, the E. coli
      O157:H7 count reduction on cantaloupe rind and cup apples reached 2.5 and 2.3 log
      CFU/cm2, respectively, when the flow velocity increased from 0.0 to 0.8 m/min.
      Agitation conducted at the bottom of the treatment chamber reduced the E. coli
      O157:H7 population on cut apples by 1.2 log CFU/cm2 in 3 min, whereas in the
      treatment with the agitation over the top of the chamber, the survival count of
      E. coli O157:H7 was reduced by only 0.8 log CFU/cm2. The experimental data were
      used to fit four microbial reduction kinetic models. It was found that E. coli
      O157:H7 reduction from the fruit surfaces was best described by the Weibull
      model. These findings may be useful in designing produce wash systems for
      achieving enhanced pathogen reduction and improved produce quality and safety.

PMID- 18044432
TI  - Comparison of antibiogram, staphylococcal enterotoxin productivity, and coagulase
      genotypes among Staphylococcus aureus isolated from animal and vegetable sources
      in Korea.
AB  - Staphylococcal food poisoning is caused by enterotoxin-producing Staphylococcus
      aureus. We investigated the prevalence of such organisms in samples of bovine
      mastitic milk (n = 714), raw meat (n = 139), and vegetables (n = 616). We
      determined the degrees of relatedness of isolates as indicated by antibiogram,
      staphylococcal enterotoxin (SE) productivity, and coagulase gene restriction
      fragment length polymorphism analysis. We examined 297 S. aureus isolates and
      found SE production in 57 (31.8%), 4 (7.8%), and 49 (73.1%) isolates from raw
      milk, raw meat, and vegetables, respectively. A high proportion of the isolates
      obtained from milk produced more than two types of toxins (mainly SEA, SEB,
      and/or SEC), whereas isolates from raw meat and vegetables primarily produced SEA
      alone. Most isolates were sensitive to cephalothin (97.6%), gentamicin (80.8%),
      erythromycin (79.5%), and tetracycline (72.7%), but were resistant to penicillin
      (90.2%) and ampicillin (88.9%). The proportion of antibiotic-resistant isolates
      differed according the source of the bacteria; the milk and vegetable isolates
      were more resistant to penicillin and ampicillin than were the meat isolates (P <
      0.05), whereas tetracycline resistance was limited to the milk and vegetables
      isolates. The coagulase genotypes (I to XII) varied with the source of the
      organism, and only a few genotypes prevailed in each source: II (42.4%) and IV
      (24%) types in isolates from milk, IX (35.3%) and XI (45%) from raw meat, and III
      (40.3%) and XII (32.8%) from vegetables. These findings suggest that remarkable
      differences exist in antibiogram, SE productivity, and coagulase genotypes,
      resulting in limited clonal transmission of S. aureus into various food sources.
      As enterotoxin production only occurs when S. aureus grows to high numbers,
      staphylococcal food poisoning can be prevented by proper refrigeration.

PMID- 18044433
TI  - Evaluation of logistic processing to reduce cross-contamination of commercial
      broiler carcasses with Campylobacter spp.
AB  - Cross-contamination of broiler carcasses with Campylobacter is a large problem in
      food production. Here, we investigated whether the contamination of broilers
      carcasses from Campylobacter-negative flocks can be avoided by logistic
      scheduling during processing. For this purpose, fecal samples were collected from
      several commercial broiler flocks and enumerated for Campylobacter spp. Based on
      enumeration results, flocks were categorized as Campylobacter negative or
      Campylobacter positive. The schedule of processing included the testing of
      Campylobacter-positive flocks before or after the testing of Campylobacter
      negative flocks. During processing, flocks were also sampled for Campylobacter
      spp. before and after chilling. Campylobacter strains were identified with
      multiplex PCR and analyzed for relatedness with pulsed-field gel electrophoresis.
      Our results show that Campylobacter-negative flocks were indeed contaminated with
      Campylobacter strains originating from previously processed Campylobacter
      positive flocks. Campylobacter isolates collected from carcasses originating from
      different farms processed on the same day showed similar pulsed-field gel
      electrophoresis patterns, confirming cross-contamination. These findings suggest
      that a simple logistic processing schedule can preserve the Campylobacter
      negative status of broiler carcasses and result in products with enhanced food
      safety.

PMID- 18044434
TI  - Prevalence of Escherichia coli O157:H7 in the American bison (Bison bison).
AB  - Bison is becoming a popular meat source for consumers, but very little is known
      about the bison's status with respect to Escherichia coli O157:H7. We conducted a
      study to determine the prevalence and identify virulence genes and pulsed-field
      genetic types of E. coli O157:H7 in bison. Rectal contents and rectoanal mucosal
      swab (RAMS) samples were collected from a total of 342 bison at slaughter on
      seven different dates. Isolation of E. coli O157:H7 was by enrichment,
      immunomagnetic separation, and plating on selective medium, and identification
      was based on sorbitol fermentation reaction, indole production, and O157
      agglutination test. An overall E. coli O157:H7 prevalence of 47.4% was observed.
      Fecal prevalence across sampling days ranged from 17 to 83%, with an average of
      42.1%. The prevalence in the rectoanal mucosal region ranged from 2.2 to 50%,
      with an average of 19.9%. All E. coli O157:H7 isolates (n = 212) possessed eae,
      hlyA, fliC, and stx2 genes. The antiterminator Q gene, Q933, was present in 50.7%
      of fecal and 38% of RAMS isolates, and Q21 was present in 52.1% of fecal and
      61.5% of RAMS isolates. The pulsed-field gel electrophoresis analysis of isolates
      revealed 11 types (> 95% Dice similarity) and 19 subtypes (100% Dice similarity).
      Two pulsed-field genetic types accounted for 76.4% of total isolates. Our study
      suggests that the prevalence of E. coli O157:H7 in rectal contents or on rectal
      mucosa of bison is variable, but relatively high overall and bison could serve as
      an important reservoir for human infection.

PMID- 18044435
TI  - Efficacy of dose regimen and observation of herd immunity from a vaccine against
      Escherichia coli O157:H7 for feedlot cattle.
AB  - A clinical trial was conducted to test the effect of a vaccine product containing
      type III secreted proteins of Escherichia coli O157:H7 on the probability that
      feedlot steers shed E. coli O157:H7 in feces. Six hundred eight same-source
      steers were utilized. Of these, 480 steers were assigned randomly to 60 pens
      (eight head per pen) and to one of four vaccination treatments (120 cattle per
      treatment, two head per treatment per pen). The four treatments were (i) no
      vaccination; (ii) one dose, vaccinated once at reimplant (day 42); (iii) two
      doses, vaccinated on arrival (day 0) and again at reimplant (day 42); and (iv)
      three doses, vaccinated on arrival (day 0), on day 21, and again at reimplant
      (day 42). The remaining 128 steers were assigned randomly to 12 pens within the
      same feedlot to serve as unvaccinated external controls. The probability of
      detecting E. coli O157:H7 among cattle receiving different doses of vaccine was
      compared with that of unvaccinated external control cattle, accounting for
      clustering by repeated measures, block, and pen and fixed effects of vaccine,
      corn product, and test period. Vaccine efficacy of receiving one, two, and three
      doses of vaccine was 68, 66, and 73%, respectively, compared with cattle in pens
      not receiving vaccine. Cattle receiving three doses of vaccine were significantly
      less likely to shed E. coli O157:H7 than unvaccinated cattle within the same pen.
      Unvaccinated cattle housed with vaccinated cattle were 59% less likely to shed E.
      coli O157:H7 than cattle in pens not receiving vaccine, likely because they
      benefited from herd immunity. This study supports the hypothesis that vaccination
      with this vaccine product effectively reduces the probability for cattle to shed
      E. coli O157:H7. There was no indication that the vaccine affected performance or
      carcass quality. In addition, we found that vaccinating a majority of cattle
      within a pen offered a significant protective effect (herd immunity) to
      unvaccinated cattle within the same pen.

PMID- 18044436
TI  - Effect of a vaccine product containing type III secreted proteins on the
      probability of Escherichia coli O157:H7 fecal shedding and mucosal colonization
      in feedlot cattle.
AB  - Preharvest intervention strategies to reduce Escherichia coli O157:H7 in cattle
      have been sought as a means to reduce human foodborne illness. A blinded clinical
      trial was conducted to test the effect of a vaccine product on the probability
      that feedlot steers, under conditions of natural exposure, shed E. coli O157:H7
      in feces, are colonized by this organism in the terminal rectum, or develop a
      humoral response to the respective antigens. Steers (n = 288) were assigned
      randomly to 36 pens (eight head per pen), and pens were randomized to vaccination
      treatment in a balanced fashion within six dietary treatments of an unrelated
      nutrition study. Treatments included vaccination or placebo (three doses at 3
      week intervals). Fecal samples for culture (n = 1,410) were collected from the
      rectum of each steer on pretreatment day 0 and posttreatment days 14, 28, 42, and
      56. Terminal rectum mucosal (TRM) cells were aseptically collected for culture at
      harvest (day 57 posttreatment) by scraping the mucosa 3.0 to 5.5 cm proximal to
      the rectoanal junction. E. coli O157:H7 was isolated and identified with
      selective enrichment, immunomagnetic separation, and PCR confirmation. Vaccinated
      cattle were 98.3% less likely to be colonized by E. coli O157:H7 in TRM cells
      (odds ratio = 0.014, P < 0.0001). Diet was also associated with the probability
      of cattle being colonized (P = 0.04). Vaccinated cattle demonstrated significant
      humoral responses to Tir and O157 lipopolysaccharide. These results provide
      evidence that this vaccine product reduces E. coli O157:H7 colonization of the
      terminal rectum of feedlot beef cattle under conditions of natural exposure, a
      first step in its evaluation as an effective intervention for food and
      environmental safety.

PMID- 18044437
TI  - Listeria prevalence and Listeria monocytogenes serovar diversity at cull cow and
      bull processing plants in the United States.
AB  - Listeria monocytogenes, the causative agent of epidemic and sporadic listeriosis,
      is routinely isolated from many sources, including cattle, yet information on the
      prevalence of Listeria in beef processing plants in the United States is minimal.
      From July 2005 through April 2006, four commercial cow and bull processing plants
      were sampled in the United States to determine the prevalence of Listeria and the
      serovar diversity of L. monocytogenes. Samples were collected during the summer,
      fall, winter, and spring. Listeria prevalence on hides was consistently higher
      during cooler weather (28 to 92% of samples) than during warmer weather (6 and
      77% of samples). The Listeria prevalence data collected from preevisceration
      carcass ranged from undetectable in some warm season samples to as high as 71%
      during cooler weather. Listeria on postintervention carcasses in the chill cooler
      was normally undetectable, with the exception of summer and spring samples from
      one plant where > 19% of the carcasses were positive for Listeria. On hides, L.
      monocytogenes serovar 1/2a was the predominant serovar observed, with serovars
      1/2b and 4b present 2.5 times less often and serovar 1/2c not detected on any
      hides sampled. L. monocytogenes serovars 1/2a, 1/2c, and 4b were found on
      postintervention carcasses. This prevalence study demonstrates that Listeria
      species are more prevalent on hides during the winter and spring and that
      interventions being used in cow and bull processing plants appear to be effective
      in reducing or eliminating Listeria contamination on carcasses.

PMID- 18044438
TI  - Variable number of tandem repeats and pulsed-field gel electrophoresis cluster
      analysis of enterohemorrhagic Escherichia coli serovar O157 strains.
AB  - Ninety-five enterohemorrhagic Escherichia coli serovar O157 strains, including 30
      strains isolated from 13 intrafamily outbreaks and 14 strains isolated from 3
      mass outbreaks, were studied by pulsed-field gel electrophoresis (PFGE) and
      variable number of tandem repeats (VNTR) typing, and the resulting data were
      subjected to cluster analysis. Cluster analysis of the VNTR typing data revealed
      that 57 (60.0%) of 95 strains, including all epidemiologically linked strains,
      formed clusters with at least 95% similarity. Cluster analysis of the PFGE
      patterns revealed that 67 (70.5%) of 95 strains, including all but 1 of the
      epidemiologically linked strains, formed clusters with 90% similarity. The number
      of epidemiologically unlinked strains forming clusters was significantly less by
      VNTR cluster analysis than by PFGE cluster analysis. The congruence value between
      PFGE and VNTR cluster analysis was low and did not show an obvious correlation.
      With two-step cluster analysis, the number of clustered epidemiologically
      unlinked strains by PFGE cluster analysis that were divided by subsequent VNTR
      cluster analysis was significantly higher than the number by VNTR cluster
      analysis that were divided by subsequent PFGE cluster analysis. These results
      indicate that VNTR cluster analysis is more efficient than PFGE cluster analysis
      as an epidemiological tool to trace the transmission of enterohemorrhagic E. coli
      O157.

PMID- 18044439
TI  - Resistance of Listeria monocytogenes F2365 cells to synthetic gastric fluid is
      greater following growth on ready-to-eat deli turkey meat than in brain heart
      infusion broth.
AB  - Ready-to-eat (RTE) deli meats have been categorized as high-risk foods for
      contraction of foodborne listeriosis. Several recent listeriosis outbreaks have
      been associated with the consumption of RTE deli turkey meat. In this study, we
      examined whether the growth of Listeria monocytogenes F2365 on commercially
      prepared RTE deli turkey meat causes listerial cells to become more resistant to
      inactivation by synthetic gastric fluid (SGF). Listerial cells grown on turkey
      meat to late logarithmic-early stationary phase were significantly more resistant
      to SGF at pH 7.0, 5.0, or 3.5 than listerial cells grown in brain heart infusion
      (BHI) broth. The pH was lower in the fluid in packages of turkey meat than in BHI
      broth (6.5 versus 7.5). However, listerial cells grown in BHI broth adjusted to a
      lower pH (6.0) did not exhibit enhanced resistance to SGF. The lesser resistance
      to SGF of listerial cells grown in BHI broth may be due, in part, to the presence
      of glucose (0.2%). This study indicates the environment presented by the growth
      of L. monocytogenes on deli turkey meat affects its ability to survive conditions
      it encounters in the gastrointestinal tract.

PMID- 18044440
TI  - Prevalence, types, and geographical distribution of Listeria monocytogenes from a
      survey of retail Queso Fresco and associated cheese processing plants and dairy
      farms in Sonora, Mexico.
AB  - In the first part of this study, samples were collected from farms, cheese
      processing plants (CPPs), and retail markets located in various geographical
      areas of Sonora, Mexico, over a 12-month period during the summer of 2004 and
      winter of 2005. Four (all Queso Fresco [QF] from retail markets) of 349 total
      samples tested positive for Listeria monocytogenes (Lm). Of these four positive
      samples, three were collected in the northern region and one in the southern
      region of Sonora. Additionally, two were collected during the winter months, and
      two were collected during the summer months. For the second part of the study, a
      total of 39 samples from a farm, a CPP, and retail markets were collected and
      processed according to a combination of the Norma Oficial Mexicana NOM-143-SSA1
      1995.10 method (NOM) and the U.S. Food and Drug Administration (FDA)
      Bacteriological Analytical Manual method, and 27 samples from these same
      locations were collected and processed according to the U.S. Department of
      Agriculture Food Safety and Inspection Service method (USDA-FSIS). The NOM-FDA
      method recovered the pathogen from 6 (15%) of 39 samples (one cheese and five
      product contact surfaces), while the USDA-FSIS method recovered the pathogen from
      5 (18.5%) of 27 samples (all product contact surfaces). In addition, the 40
      isolates recovered from the 15 total samples that tested positive for Lm grouped
      into five distinct pulsotypes that were ca. 60% related, as determined by pulsed
      field gel electrophoresis analysis. The results of this study confirmed a 3.4%
      prevalence of Lm in QF collected from retail markets located in Sonora and no
      appreciable difference in the effectiveness of either the NOM-FDA or USDA-FSIS
      method to recover the pathogen from cheese or environmental samples.

PMID- 18044441
TI  - Mathematical modeling and assessment of microbial migration during the sprouting
      of alfalfa in trays in a nonuniformly contaminated seed batch using Enterobacter
      aerogenes as a surrogate for Salmonella Stanley.
AB  - Raw seed sprouts have been implicated in several food poisoning outbreaks in the
      past 10 years. The U.S. Food and Drug Administration recommends that sprout
      growers use interventions (such as testing of spent irrigation water) to control
      the presence of pathogens in the finished product. During the sprouting process,
      initially low concentrations of pathogen may increase, and contamination may
      spread within a batch of sprouting seeds. A model of pathogen growth as a
      function of time and distance from the contamination spot during the sprouting of
      alfalfa in trays has been developed with Enterobacter aerogenes. The probability
      of detecting contamination was assessed by logistic regression at various time
      points and distances by sampling from sprouts or irrigation water. Our results
      demonstrate that microbial populations and possibility of detection were greatly
      reduced at distances of > or = 20 cm from the point of contamination in a seed
      batch during tray sprouting; however, the probability of detecting microbial
      contamination at distances less than 10 cm from the point of inoculation was
      almost 100% at the end of the sprouting process. Our results also show that
      sampling irrigation water, especially large volumes of water, is highly effective
      at detecting contamination: by collecting 100 ml of irrigation water for membrane
      filtration, the probability of detection was increased by three to four times
      during the first 6 h of seed germination. Our findings have quantified the degree
      to which a small level of contamination will spread throughout a tray of
      sprouting alfalfa seeds and subsequently be detected by either sprout or
      irrigation water sampling.

PMID- 18044443
TI  - Inhibition of Bacillus cereus in milk fermented with kefir grains.
AB  - The effects of kefir-fermented milk were tested against a toxigenic strain of
      Bacillus cereus. The incubation of milk with B. cereus spores plus 5% kefir
      grains prevented spore germination and growth of vegetative forms. In contrast,
      when 1% kefir grains was used, no effects were observed. The presence of
      metabolically active kefir grains diminished titers of nonhemolytic enterotoxin
      A, as assessed by enzyme-linked immunosorbent assay. During fermentation, kefir
      microorganisms produce extracellular metabolites such as organic acids, which
      could play a role in the inhibition of spore germination and growth of B. cereus,
      although the effect of other factors cannot be ruled out. Results of the present
      study show that kefir-fermented milk is able to antagonize key mechanisms
      involved in the growth of B. cereus as well as interfere with the biological
      activity of this microorganism.

PMID- 18044442
TI  - Identification and antimicrobial susceptibility of lactic acid bacteria from
      retail fermented foods.
AB  - One important safety criterion of using lactic acid bacteria (LAB) in food
      applications is to ensure that they do not carry transferable antimicrobial
      resistance (AR) determinants. In this study, 63 LAB belonging to six genera,
      Streptococcus, Lactobacillus, Lactococcus, Enterococcus, Leuconostoc, and
      Pediococcus, were recovered from 28 retail fermented food products in Maryland,
      identified to species with 16S-23S rRNA spacer PCRs, and characterized for
      antimicrobial susceptibility against eight antimicrobials. Besides intrinsic
      resistance to ciprofloxacin or vancomycin in some lactobacilli, tetracycline
      resistance was observed in two Streptococcus thermophilus isolates from one
      cheese and one sour cream sample and was associated with the presence of a
      nonconjugative tet(S) gene. The results indicated a low level of AR among
      naturally occurring and starter LAB cultures in fermented dairy and meat products
      in the United States; therefore, the probability for foodborne LAB to serve as
      reservoirs of AR is low. Further studies involving a larger sample size are
      needed to assess the potential risk of AR gene transfer from LAB in fermented
      food products.

PMID- 18044444
TI  - Association of prophage antiterminator Q alleles and susceptibility to food
      processing treatments applied to Escherichia coli O157 in laboratory media.
AB  - Resistance of Escherichia coli O157 to inactivation by high-pressure processing,
      heat, and UV and gamma radiation was associated with the allele of the prophage
      encoded antiterminator Q gene present upstream of the Shiga toxin gene stx2.
      Increased processing may be required to kill certain strains of E. coli O157, and
      the choice of strains used as surrogate markers for processing efficiency is
      critical.

PMID- 18044445
TI  - Survival and growth of Listeria monocytogenes in broth as a function of
      temperature, pH, and potassium lactate and sodium diacetate concentrations.
AB  - The objective of this study was to determine the antimicrobial effect of a
      combination of potassium lactate and sodium diacetate (0, 1.8, 3, and 4.5%;
      PURASAL P Opti. Form 4, 60% solution) on the survival and growth of Listeria
      monocytogenes Scott A in pH-adjusted broth (5.5, 6.0, 6.5, and 7.0) stored at 4,
      10, 17, 24, 30, and 37 degrees C. Appropriate dilutions of broth were enumerated
      by spiral plating on tryptose agar and counted with an automated colony counter.
      Growth data were iteratively fit, using nonlinear regression analysis to a three
      phase linear model, using GraphPad PRISM. At pH 5.5, the combination of lactate
      diacetate fully inhibited (P < 0.001) the growth of L. monocytogenes at all four
      levels and six temperatures. At pH 6.0, addition of 1.8% lactate-diacetate
      reduced (P < 0.001) the specific growth rate of L. monocytogenes and increased
      lag time; however, 3 and 4.5% completely inhibited the growth at the six
      temperatures studied. Efficacy of the lactate-diacetate mixture was decreased as
      pH increased and incubation temperature increased. Thus, at pH 6.5, at least 3%
      was required to retard (P < 0.001) the growth of L. monocytogenes in broth. There
      was a limited effect of the lactate-diacetate level on the specific growth rate
      of the pathogen at pH 7.0. However, 1.8 and 3% significantly lengthened the lag
      time at 4 and 10 degrees C. These results suggest that 1.8% of lactate-diacetate
      mixture can be used as a substantial hurdle to the growth of L. monocytogenes
      when refrigerated temperatures are maintained for products with pH less than 6.5.

PMID- 18044446
TI  - Effects of essential oils of oregano and nutmeg on growth and survival of
      Yersinia enterocolitica and Listeria monocytogenes in barbecued chicken.
AB  - The in vitro effects of plant essential oils (EOs) against pathogenic bacteria
      are well known, yet few studies have addressed the effects of these compounds
      against pathogens associated with ready-to-cook foods. Experiments were conducted
      to determine the effectiveness of oregano and nutmeg EOs on the growth and
      survival of Yersinia enterocolitica and Listeria monocytogenes in broth culture
      and in Iranian barbecued chicken. Ready-to-cook Iranian barbecued chicken was
      prepared according to the common practice with 1, 2, and 3 microl/g of oregano
      and nutmeg EOs. The test and control (without EOs) samples were inoculated with
      Y. enterocolitica and L. monocytogenes to a final concentration of 6 to 7 log
      CFU/g and stored at 3, 8, and 20 degrees C. Microorganisms were counted just
      before and at 24, 48, and 72 h after storage based on growth on Yersinia
      selective agar supplemented with cefsulodine, igrasan, and novobiocin and on
      Listeria selective agar supplemented with nalidixic acid and acriflavin. In the
      broth culture system, the nutmeg EO had a greater effect on L. monocytogenes (MIC
      = 0.20 nicrol/ml) than did the oregano EO (MIC = 0.26 microl/ml). However, the
      oregano EO had a greater effect on Y. enterocolitica (MIC = 0.16 microl/ml) than
      did the nutmeg EO (MIC = 0.25 microl/ml). In ready-to-cook Iranian barbecued
      chicken, the log CFU per gram of both bacteria after up to 72 h of incubation was
      not decreased significantly by various combinations of oregano and nutmeg EOs (1,
      2, and 3 microl/g) and storage temperatures (3, 8, and 20 degrees C) when
      compared with control samples (without EOs). Although examination of spices in
      culture media can yield accurate microbiological data, without complementary
      tests in foods these data are of limited value for assessing food safety.

PMID- 18044447
TI  - Antimicrobial efficacy of eugenol microemulsions in milk against Listeria
      monocytogenes and Escherichia coli O157:H7.
AB  - The antimicrobial activity of eugenol microemulsions (eugenol encapsulated in
      surfactant micelles) in ultrahigh-temperature pasteurized milk containing
      different percentages of milk fat (0, 2, and 4%) was investigated. Antimicrobial
      microemulsions were prepared from a 5% (wt) aqueous surfactant solution (Surfynol
      485W) with 0.5% (wt) eugenol. Two strains each of Listeria monocytogenes and
      Escherichia coli O157:H7 previously shown to be the least and most resistant to
      the microemulsion in microbiological media were used to inoculate sterile milk
      (10(4) CFU/ml). Samples were withdrawn and plated at 0, 1, 3, 6, 12, and 24 h for
      enumeration. Microemulsions completely prevented growth of L. monocytogenes for
      up to 48 h in skim milk and reduced both strains of E. coli O157:H7 to less than
      detectable levels in less than 1 h. Similarly, in 2% fat milk, eugenol-Surfynol
      combinations reduced both strains of E. coli O157:H7 to less than detectable
      levels in less than 1 h but only increased the lag phase of both strains of L.
      monocytogenes. In full-fat milk (4% fat), microemulsions inhibited growth of the
      least resistant strains of L. monocytogenes and E. coli but were ineffective
      against the two resistant strains. Unencapsulated eugenol was slightly more or as
      inhibitory as microemulsions against target pathogens. Results were attributed to
      diffusional mass transport of antimicrobials from microemulsions to the
      macroemulsion (milk). Results suggest that food composition, especially fat
      level, may affect the efficiency of targeting of foodborne pathogens with
      surfactant-encapsulated antimicrobials.

PMID- 18044448
TI  - Determination of 5-log reduction times for food pathogens in acidified cucumbers
      during storage at 10 and 25 degrees C.
AB  - Outbreaks of acid-resistant foodborne pathogens in acid foods with pH values
      below 4.0, including apple cider and orange juice, have raised concerns about the
      safety of acidified vegetable products. For acidified vegetable products with pH
      values between 3.3 and 4.6, previous research has demonstrated that thermal
      treatments are needed to achieve a 5-log reduction in the numbers of Escherichia
      coli O157:H7, Listeria monocytogenes, or Salmonella enterica. For some acidified
      vegetable products with a pH of 3.3 or below, heat processing can result in
      unacceptable product quality. The purpose of this study was to determine the
      holding times needed to achieve a 5-log reduction in E. coli O157:H7, L.
      monocytogenes, and S. enterica strains in acidified vegetable products with
      acetic acid as the primary acidulant, a pH of 3.3 or below, and a minimum
      equilibrated temperature of 10 degrees C. We found E. coli O157:H7 to be the most
      acid-resistant microorganism for the conditions tested, with a predicted time to
      achieve a 5-log reduction in cell numbers at 10 degrees C of 5.7 days, compared
      with 2.1 days (51 h) for Salmonella or 0.5 days (11.2 h) for Listeria. At 25
      degrees C, the E. coli O157:H7 population achieved a 5-log reduction in 1.4 days
      (34.3 h).

PMID- 18044449
TI  - Occurrence of mycotoxin patulin in apple-based products marketed in Tunisia.
AB  - An investigation on the presence of mycotoxin patulin was performed on 71 apple
      juices and concentrates and 21 infant fruit purees purchased from retail outlets
      or producers in Tunisia, by reversed-phase high-performance liquid chromatography
      using a C18 column with UV detection at 276 nm, keeping the recovery higher than
      96% for spiking levels ranging between 30 and 100 ppb. The detection limit of the
      method was found to be 5 ppb. The findings showed that 12% of the samples locally
      produced in Tunisia were contaminated by patulin, with a maximum level of 6 ppb,
      and 5% of the samples imported and marketed in Tunisia were contaminated at a
      mean level less than 6 ppb. No detectable patulin contaminations for apple cider
      and infant fruit puree samples were found.

PMID- 18044450
TI  - Species-specific identification of penicillium linked to patulin contamination.
AB  - Certain species of Penicillium have been reported to produce the mycotoxin
      patulin, and research was undertaken to identify these with the use of
      oligonucleotide primer pairs. Species examined were found in food, plants, and
      soil and were reported to produce patulin. Penicillium expansum is the most
      commonly detected species linked to the presence of patulin in apple juice. At
      least 10 different enzymes are involved in the patulin biosynthetic pathway,
      including the isoepoxydon dehydrogenase (idh) gene. Based on nucleotide sequences
      previously determined for the idh gene in Penicillium species, PCR primers were
      designed for the species-specific detection of patulin-producing species. The 5'
      primers were based on differences in the second intron of the idh gene. To ensure
      that the primer pairs produced a PCR product restricted to the species for which
      it was designed, and not to unrelated species, all of the primer pairs were
      tested against all of the Penicillium species. With one exception, it was
      possible to detect a reaction only with the organism of interest. The primer pair
      for Penicillium griseofulvum also amplified DNA from Penicillium dipodomyicola, a
      closely related species; however, it was possible to distinguish between these
      two species by doing a second amplification, with a different primer pair
      specific only for P. dipodomyicola. Consequently, with different primer sets, it
      was possible to identify individual patulin-producing species of Penicillium.

PMID- 18044451
TI  - Preparation-free method for detecting Escherichia coli O157:H7 in the presence of
      spinach, spring lettuce mix, and ground beef particulates.
AB  - We show the detection of 100 cells per ml of Escherichia coli O157:H7 in the
      presence of spinach, spring lettuce mix, and ground beef washes and particulate
      matter with piezoelectric-excited millimeter-sized cantilever (PEMC) sensors. The
      PEMC sensors (sensing area, 2 mm2) were immobilized with polyclonal antibody
      specific to E. coli O157:H7 (EC) and were exposed to 10 aqueous washes of locally
      purchased spinach, spring lettuce mix, and ground beef for testing if EC was
      present. Absence of resonance frequency shift indicated that EC was not present
      in the 30 samples tested. Following the last sample in each food matrix, 1,000
      cells per ml of EC were spiked into the sample container, and resonance frequency
      change was monitored. The total resonance frequency change was 880 +/- 5, 1,875
      +/- 8, and 1,417 +/- 4 Hz for spinach, spring lettuce mix, and ground beef,
      respectively. A mixture of the three food matrices spiked with 100 cells per ml
      of EC gave a sensor response of 260 +/- 15 Hz. The resonance frequency changes
      are approximately 40% lower than our previously reported study on ground beef. It
      is suggested that the reduction in sensitivity is due to differences in pathogen
      adherence to food matrices, which affects target binding to the sensor surface.
      We conclude that detection selectivity is conserved in the three food matrices
      examined and that the magnitude of sensor response is a function of the food
      matrix.

PMID- 18044452
TI  - Impact of dilution ratios on Listeria monocytogenes growth during University of
      Vermont medium enrichment of deli meats.
AB  - In the U.S. Department of Agriculture (USDA) method for Listeria detection, a 25
      g composite food sample is enriched in 225 ml of University of Vermont medium
      (UVM), giving a detection limit of 0.04 CFU/g. However, in a recent large-scale
      four-state deli meat survey for L. monocytogenes, 125-g samples enriched in 1,125
      ml of UVM were requested to increase the detection limit to 0.008 CFU/g. To
      circumvent problems associated with large volumes of UVM, the impact on L.
      monocytogenes growth of lower dilution ratios used for enrichment and most
      probable-number (MPN) detection was compared with the results obtained using the
      conventional 1:10 dilution. In this study, 125-g samples of cured turkey, uncured
      turkey, ham, and roast beef were inoculated with a six-strain L. monocytogenes
      cocktail to contain approximately 1 x 10(3) CFU/g. This cocktail was then diluted
      1:3, 1:5, or 1:10 in UVM, homogenized, enriched at 30 degrees C, and periodically
      plated on modified Oxford agar to determine generation times during 24 h of
      incubation. The same enrichment protocol was also assessed in a three-tube MPN
      assay using 125-g samples inoculated with L. monocytogenes to contain
      approximately 1 CFU/g. The effects of two homogenization methods, stomaching and
      pulsifying, on Listeria growth were compared using oven-roasted turkey breast
      diluted 1:3, 1:5, and 1:10 in UVM. Overall, the growth rates, generation times,
      and MPN values for each of the four selected deli meats were similar (P > 0.05)
      using UVM enrichment ratios of 1:3, 1:5, and 1:10, with no significant (P > 0.05)
      differences in L. monocytogenes growth rate or generation time between
      experiments using pulsifying and stomaching. These findings indicate that lower
      volumes of UVM can be used in the USDA procedure when examining deli meats
      without compromising Listeria recovery.

PMID- 18044453
TI  - Comparison of dry sheet media and conventional agar media methods for enumerating
      yeasts and molds in food.
AB  - A study was done to compare Nissui Compact Dry Yeast and Mold plates (CDYM), 3M
      Petrifilm Yeast and Mold count plates (PYM), dichloran-rose bengal
      chloramphenicol (DRBC) agar, and dichloran 18% glycerol (DG18) agar for
      enumerating yeasts and molds naturally occurring in 97 foods (grains, legumes,
      raw fruits and vegetables, nuts, dairy products, meats, and miscellaneous
      processed foods and dry mixes). Correlation coefficients for plates incubated for
      5 days were DG18 versus DRBC (0.93), PYM versus DRBC (0.81), CDYM versus DG18
      (0.81), PYM versus DG18 (0.80), CDYM versus DRBC (0.79), and CDYM versus PYM
      (0.75). The number of yeasts and molds recovered from a group of foods (n = 32)
      analyzed on a weight basis (CFU per gram) was not significantly different (alpha
      = 0.05) when samples were plated on DRBC, DG18, PYM, or CDYM. However, the order
      of recovery from foods (n = 65) in a group analyzed on a unit or piece basis, or
      a composite of both groups (n = 97), was DRBC > DG18 = CDYM > PYM. Compared with
      PYM, CDYM recovered equivalent, significantly higher (alpha = 0.05) or
      significantly lower (alpha = 0.05) numbers of yeasts and molds in 51.5, 27.8, and
      20.6%, respectively, of the 97 foods tested; respective values were 68.8, 15.6,
      and 15.6% in the small group (n = 32) and 43.1, 33.8, and 23.1% in the large
      group (n = 65) of foods. The two groups contained different types of foods, the
      latter consisting largely (73.8%) of raw fruits (n = 16) and vegetables (n = 32).
      Differences in efficacy of the four methods in recovering yeasts and molds from
      foods in the two groups are attributed in part to differences in genera and
      predominant mycoflora. While DG18 agar, CDYM, and PYM appear to be acceptable for
      enumerating yeasts and molds in the foods analyzed in this study, overall, DRBC
      agar recovered higher numbers from the 97 test foods, thereby supporting its
      recommended use as a general purpose medium for mycological analysis.

PMID- 18044454
TI  - Preliminary analysis of the lipase gene (gehM) expression of Staphylococcus
      xylosus in vitro and during fermentation of naturally fermented sausages (in
      situ.
AB  - Coagulase-negative catalase-positive cocci (CNCPC) play a very important role
      during the fermentation of sausages. In particular, they are involved in the
      aroma formation of the final product, because they release lipases that are able
      to free short-chain fatty acids that are contributing to the sensory
      characteristics of the fermented sausage. Few studies have been undertaken to
      elucidate the regulation of lipase gene expression in Staphylococcus xylosus by
      substrate molecules or products of lipolysis. The aim of this study was to
      analyze the gehM gene expression of S. xylosus DSMZ 6179 in vitro with growth
      media containing different concentrations of lipids and in situ during the
      maturation of fermented sausages. The results obtained suggest that a
      concentration that increases in triglycerides in the growth medium suppresses the
      expression of the lipase gene.

PMID- 18044455
TI  - High-added-value antioxidants obtained from the degradation of wine phenolics by
      Lactobacillus plantarum.
AB  - Disposal of the waste from wine production has long been a problem for wineries,
      mainly because of the presence of phenolic compounds. In this study, we analyzed
      the antimicrobial activities of 10 wine phenolic compounds against Lactobacillus
      plantarum strains. Inhibition increased in this order: catechin = gallic acid <
      epicatechin = salicylic acid < methyl gallate = caffeic acid < ferulic acid =
      tryptophol < p-coumaric acid. The obtained results indicated that L. plantarum is
      able to grow in the presence of high concentrations of some wine phenolic
      compounds. Of the 10 compounds analyzed, only the hydroxycinnamic acids, gallic
      acid, and methyl gallate were metabolized by the four L. plantarum strains
      studied. Results also revealed that 4-vinylphenol and 4-vinylguaiacol are
      originated from p-coumaric and ferulic acids. These phenolic compounds are
      valuable intermediates in the biotechnological production of new fragrances. In
      addition, gallic acid and its ester, methyl gallate, are metabolized to produce
      the powerful antioxidant pyrogallol. Therefore, it might be possible to use L.
      plantarum strains to obtain high-added-value antioxidants from the degradation of
      phenolic compounds found in wine wastes.

PMID- 18044456
TI  - Approaches for reducing Salmonella in pork production.
AB  - Salmonellosis is an important disease in humans and is associated with
      contaminated food, including pork products. Salmonella infection is invasive in
      humans, but it usually remains latent within the swine population, creating
      reservoirs for carcass contamination. Although abattoirs implement stringent
      procedures during carcass processing, some raw pork products still have
      Salmonella contamination. To reduce the presence of Salmonella, a dynamic picture
      of the pork production chain is needed that includes management practices aimed
      at health and welfare of swine and practices within swine operations that affect
      the environment and community health. Swine practices indirectly influence the
      spread of zoonotic enteric pathogens. Pathogens in food animals can escape
      detection, and critical control points often are missed. Preharvest growth of
      swine by enhancement of normal gut flora and targeting intestinal pathogens
      through nonantibiotic approaches might improve food safety and reduce antibiotic
      residues. In light of the threat posed by multidrug-resistant pathogens, old
      dogma is being revisited with optimism for potential utility in promoting pre-
      and postharvest pork safety. This review includes possible approaches that can be
      implemented in swine operations and postslaughter during pork processing with
      simultaneous omission of subtherapeutic antibiotics to control Salmonella. We
      emphasize the vital roles of the veterinarians, pig producers, industry, food
      research scientists, and government guidelines for the strategic implementation
      of approaches to Salmonella control across the pork production and processing
      chains.

PMID- 18044457
TI  - Clinical significance of inter-arm pressure difference and ankle-brachial
      pressure index in patients with suspected coronary artery disease.
AB  - BACKGROUND: Although measuring blood pressure at the bilateral brachia is common
      in medical practice, its clinical significance in patients with suspected
      coronary artery disease (CAD) has not been fully clarified. METHODS: To define
      the significance of inter-arm systolic blood pressure difference in patients with
      suspected CAD, and to assess the relationship between inter-arm pressure
      difference and CAD, simultaneous brachial and ankle blood pressure measurements
      and stress myocardial single-photon emission computed tomography (SPECT) were
      performed in 386 consecutive patients with suspected CAD, excluding those with
      previous myocardial infarction or coronary revascularization. RESULTS: Subclavian
      artery stenosis, defined as > or = 15 mmHg inter-arm systolic blood pressure
      difference, was found in 27 patients (7%). Age (65 +/- 12 vs 65 +/- 11 years),
      male sex (21/27 vs 244/359), prevalence of hypertension(63% vs 56%),
      hypercholesterolemia (63% vs 62%), diabetes mellitus(33% vs 38%), cigarette
      smoking (44% vs 41%) and family history of CAD (15% vs 12%) were similar between
      patients with subclavian artery stenosis and those without. The incidence of
      decreased ankle-brachial pressure index (ABI) was higher (37% vs 12%, p = 0.001),
      and percentage ischemic myocardium as assessed by SPECT was greater (9.0 +/- 8.5%
      vs 5.6 +/- 6.6%, p < 0.05) in patients with subclavian artery stenosis than in
      those without. Furthermore, significant correlations were observed between inter
      arm pressure difference and percentage ischemic myocardium (r = 0.13; p = 0.01),
      and ABI (r = -0.26, p < 0.0001). Among 386 patients, 283 underwent coronary
      angiography, and 63% of those who had inter-arm blood pressure difference had
      CAD. Furthermore, 83% of those CAD patients had multi-vessel CAD, which is
      regarded as a high-risk subset for subsequent cardiac events. CONCLUSIONS: Inter
      arm pressure difference is often found in patients with suspected CAD, and is
      associated with significant CAD and peripheral artery disease. Thus, inter-arm
      pressure difference may be regarded as a simple marker for coronary and
      peripheral artery diseases.

PMID- 18044458
TI  - Positive correlation between chymase-like angiotensin II-forming activity in
      mononuclear cells and serum cholesterol level.
AB  - OBJECTIVES: The local renin-angiotensin system is important in cardiovascular
      diseases. The present study examined the association between angiotensin (Ang) II
      forming activity in fractionated peripheral leukocytes and atherosclerotic risks
      such as blood pressure, smoking, age and serum cholesterol level, and used a new
      analytical approach for the measurement of chymase-like activity in peripheral
      blood to assess the relationship between the chymase-like activities in
      leukocytes and atherosclerotic risks. METHODS: Peripheral blood samples were
      obtained from normal and high blood pressure patients in the presence or absence
      of ischemic heart disease. Mononuclear cell or polymorphonuclear cell fraction of
      leukocyte was isolated by centrifugation with either Lymphoprep or Polymorphprep,
      respectively. Chymase-like, angiotensin converting enzyme, and cathepsin G
      dependent Ang II-forming activities in the homogenates of mononuclear cell or
      polymorphonuclear cell fraction were measured using Ang I as a substrate.
      RESULTS: The chymase-like Ang II-forming activity in the mononuclear cell
      fraction slightly or significantly increased in non-smoker patients with high
      blood pressure (systolic and diastolic blood pressure, p = 0.11; mean blood
      pressure, p < 0.05). Chymase-like Ang II-forming activity in the mononuclear cell
      fraction positively correlated with serum total cholesterol (p < 0.05) level.
      CONCLUSIONS: Our data indicates that chymase in mononuclear cells from peripheral
      blood is activated by high blood pressure or hypercholesterolemia.

PMID- 18044459
TI  - Prospective follow-up cardiac evaluation of children with Kawasaki disease in
      Northern India using the Japanese echocardiography criteria.
AB  - OBJECTIVES: There is no information available on the follow-up of children with
      Kawasaki disease (KD) in developing countries. This prospective study was
      undertaken to evaluate the cardiac abnormalities in a cohort of children with KD
      from a tertiary care centre in Northern India. METHODS: Twenty children with
      diagnoses of KD and followed-up for at least 3 months in the Pediatric
      Rheumatology and Immunology Clinic of the Advanced Pediatric Centre, Post
      Graduate Institute of Medical Education and Research (PGIMER), Chandigarh were
      evaluated between July 2002 to January 2006. Age of onset of disease ranged from
      12 months to 10 years. The male: female ratio was 4:1. All patients had received
      intravenous immunoglobulin (IVIG) administration in the acute stage. Chest
      radiography showed no abnormalities in the 15 patients in whom it was done.
      Electrocardiographic abnormalities were seen in 3 patients in the form of T wave
      inversion in 3, ST segment changes in 2, and prolonged PR interval in 1 patient
      which normalized on follow-up. The mean time interval between the diagnosis of KD
      and first follow-up echocardiography was 7.9 +/- 3.5 months (range 4.4-11.4
      months), which was repeated at 1 year and 2 years follow-up in patients who had
      abnormal findings. When we analyzed coronary artery diameters using Japanese
      Ministry of Health criteria, none of our patients could qualify for a diagnosis
      of coronary aneurysm. However, 3 had coronary artery diameters more than + 2 SD
      when the body surface area adjusted coronary dimensions were used. RESULTS: One
      of our patients also had increased left ventricular dimensions but also had
      normal ejection fraction and shortening fraction, and there were no regional wall
      motion abnormalities. Mitral valve was thickened in 2 patients and trivial mitral
      regurgitation was noticed in 1 patient. Repeat echocardiography done 1 year and 2
      years later on follow-up, showed persistence of thickening of the mitral valve
      leaflet in one of these but there was no regurgitation. None of our patients had
      evidence of cardiac failure, arrhythmia or myocardial infarction. There was no
      mortality in this series. Thallium scans were carried out during follow-up on 14
      patients in this cohort and 2 patients showed perfusion defects in anterior wall,
      septum and posterior wall of lateral ventricle. CONCLUSIONS: We conclude that
      significant myocardial dysfunction and coronary artery changes due to KD were
      uncommon in our cohort. We speculate that this can be attributed to the IVIG
      given to the patients during the acute phase of the illness. To the best of our
      knowledge, this is the first study on detailed cardiac follow-up of children with
      KD from a developing country.

PMID- 18044460
TI  - [Effects on proliferation ability of vascular smooth muscle cells by static
      and/or dynamic cell culture: utility of pre-seeding technique for dynamic cell
      culture].
AB  - OBJECTIVES: Conventional biomaterials are not viable, do not grow, and do not
      provide contractile effects in cardiac tissue. Foreign synthetic material may
      become thrombogenic or infected. The most recent cardiac constructs consist of
      biodegradable material which has the potential to solve these problems. However,
      dynamic three-dimensional cell culture is necessary because conventional culture
      is limited to construct tough biografts. METHODS: Vascular smooth muscle cells
      derived from rat aorta were seeded to poly-L-lactide-epsilon-capro-lactone
      copolymer in three groups; static culture group (static cell seeding + static
      cell culture), dynamic culture group (dynamic cell seeding + dynamic cell
      culture), and pre-seeding group [static cell seeding and culture for 1 week (pre
      seeding) + dynamic cell culture]. The dynamic cell culture system used an
      original spinner flask. The pre-seeding technique used static cell seeding and
      culture before dynamic culture. The three groups were evaluated by cell
      proliferation and histologic studies. RESULTS: Vascular smooth muscle cells could
      be proliferated in/on the biodegradable materials. The pre-seeding group cells
      grew much more efficiently than the other groups. Very few cells were found in
      the biodegradable materials with the dynamic groups. However, there were many
      cells in the materials with the static culture group and pre-seeding group,
      especially the pre-seeding group. CONCLUSIONS: Dynamic culture is useful for
      constructing tough biografts by the pre-seeding technique.

PMID- 18044461
TI  - Usefulness of ultrasonography in carotid arteries and combined positron emission
      tomography/ computed tomography for diagnosis of Takayasu arteritis with unusual
      presentation as acute myocardial infarction: a case report.
AB  - This unusual case of Takayasu arteritis presenting as acute myocardial infarction
      could be defined by ultrasonography and 18-fluorodeoxyglucose positron emission
      tomography (18F-FDG PET) coregistered with computed tomography (CT). A 55-year
      old male was admitted to our hospital with continuous chest pain and left-side
      neck pain. After primary percutaneous coronary intervention, elevation of
      inflammatory markers persisted and dull pain in the left side of the neck
      continued. Ultrasonography revealed characteristic wall thickening of the left
      common carotid artery and subsequent 18F-FDG PET with CT depicted positive uptake
      in the left common carotid artery and the vessel wall of the ascending aorta,
      confirming the diagnosis of Takayasu arteritis. Three months after angioplasty,
      follow-up cardiac catheterization was performed. Coronary angiography showed no
      restenosis. During the catheterization, angiography confirmed the mild stenosis
      in the long segment of the left common carotid artery and the left subclavian
      artery as well as the focal narrowing and the dilation of the abdominal aorta.
      This case shows that ultrasonography in the cervical region and combined 18F-FDG
      PET with CT may be useful in the diagnosis and evaluation of Takayasu arteritis.
      In addition, we should pay attention to underlying disease even in middle-aged or
      older male patients with acute myocardial infarction.

PMID- 18044462
TI  - [Right ventricular perforation by screw-in lead after permanent pacemaker
      implantation: a case report].
AB  - A 93-year-old man received a permanent implanted pacemaker(VVI mode) to treat
      completed atrioventricular block in our hospital. However, pacing failure
      appeared 4 days later. Computed tomography showed right ventricular perforation
      by the screw-in lead. There was no evidence of cardiac tamponade or symptoms, so
      we inserted another lead into the right ventricular outflow tract without
      removing the first lead. This patient still has the pacing lead that perforated
      the right ventricle, so careful observation will be needed even after discharge.

PMID- 18044463
TI  - [Percutaneous transluminal angioplasty using Filtrap to capture thrombus for
      chronic total occlusion of superficial femoral artery: a case report].
AB  - A 75-year-old female was admitted for cerebral infarction and arteriosclerosis
      obliterans. Computed tomography with contrast medium revealed occlusion of the
      superficial femoral artery (SFA). Percutaneous transluminal angioplasty (PTA)was
      performed for the SFA (length 30 cm), but massive thrombus was seen in the SFA.
      PTA was continued using a Filtrap deployed at the popliteal artery to prevent
      distal embolism and the thrombus was captured by the Filtrap. Finally antegrade
      blood flow was observed. However, the following day, acute stent thrombosis
      occurred and emergent PTA was performed. Suboptimal stent expansion and
      dissection were found. Balloon angioplasty was performed using a Filtrap and
      another stent was deployed. Final angiography revealed good blood flow in the
      SFA. Filtrap may reduce the risk of distal embolism during PTA for the lower
      limb.

PMID- 18044464
TI  - [A 38-year-old man with complaints of fever and lumbago].

PMID- 18044465
TI  - [Guidelines for diagnosis and treatment of aortic aneurysm and aortic dissection
      (JCS 2006)].

PMID- 18044466
TI  - [Medical informatics--today and tomorrow].
AB  - The status of medical informatics, a comparatively new biomedical discipline
      beginning to develop in the second half of the 20th century, is described at the
      transition into the 21st century. The appearance of new information and
      communication technologies, among which Internet nas special importance, was a
      major impulse to the development of medical informatics in its different fields.
      Health information systems are integrating, while at the same time, by
      distribution of their parts, they become available to the individual healthcare
      user. These processes put the problems of interoperability and standardization
      into the focus of contemporary medical informatics. The electronic health record
      is recognized as a key instrument of modern healthcare systems, and its
      development and implementation are being planned at many places. Whereas the
      research and application of medical decision support systems are stagnating, new
      disciplines have emerged such as telemedicine, cybermedicine and bioinformatics.
      The perspectives of the future development of medical informatics are described.
      In the appendix, a chronology of the development of medical informatics from its
      beginning to the present time is given.

PMID- 18044467
TI  - [Human leptospirosis in Slavonski Brod, 1995-2005].
AB  - Leptospirosis is a worlwide spread zoonosis. During the 1995-2005 period, 54
      patients with leptospirosis were recorded at the Institute of Public Health, Brod
      Posavina County, yielding an incidence rate of 1.6-8.8 per 100,000 per year. One
      (1.85 %) patient died. There were 41 (76%) males. The age of leptospirosis
      patients ranged from 15 to 77 (mean 44) years. Forty-three (79.6 %) patients were
      from rural areas, and 17%. were farmers. The most frequent serotypes were:
      australis (20%), pomona (15%), saxkoebing (10%) and grippotyphosa (7%). Thirty
      six (68.5%) leptospirosis cases were notified between July and October. A
      significant correlation (r = 0.77; P < 0.01; r2 = 59.3%) was found betwen the
      number of leptospirosis cases and average rainfall recorded one month prior to
      the diagnosis.

PMID- 18044468
TI  - [Study of quality of life in patients with multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis (MS) is a neurological impairment mostly
      affecting younger adults substantially decreasing their working and living
      abilities. Different rating scales to determine disabilities are being used:
      EDSS, NRS, and CAMBS. The objective of this study was to assess the quality of
      life in MS patients, with reference to the disease itself and its treatment,
      comparing patients with MS and a matching healthy control group. METHODS AND
      SUBJECTS: Subjects were divided into two groups, a group of patients with MS and
      a control group of healthy subjects. There were 37 MS patients, 25 women and 12
      men. Control group consisted of 51 subjects, 39 women and 12 men. There was no
      statistically significant sex difference. The mean age of the MS patients was
      45.9 +/- 12.4 years, and of control group 42.4 +/- 10.3 years; yielding no
      statistically significant difference. The severity of impairment in MS patients
      according to EDSS scale was 3 to 3.5. The quality of life determined by the
      prediction and criterion variables was studied in both MS patients groups and
      control group. All variables were graded on a 1 to 5 scale. On statistical data
      processing chi2 test and t-test were used. RESULTS AND DISCUSSION: Predictors
      referring to family history, sexual life, social life, satisfaction with
      education, job, social environment, religious life, housing status, financial
      status and present family life did not differ between the MS and control group.
      MS patients were less satisfied with their place in society, their state of
      health and ways of spending their free time. The decrease of satisfaction
      correlated with the areas generally known to be directly or indirectly affected
      by MS. As to the criterion variable of 'satisfaction with former way of life' no
      significant differences were found, since the disease did not affect previous
      life achievements. MS patients were less satisfied with their status in society,
      their state of health and ways of spending their free time. Changes occurred as a
      consequence of substantial life changes caused by the disease, results of
      treatments and circumstances in which the patients lives. Results obtained
      indicated that patients were aware of their disease, lower quality of life that
      limited their daily activities and future plans. Answers referring to the state
      of health, social status, and sexual activities did not show any statistically
      significant difference between the groups of MS patients and healthy controls,
      although it could have been expected according to the experience and customary
      expectations in such cases. CONCLUSION: MS patients are mainly satisfied with
      what they have achieved previously as young people; they become dissatisfied in
      relation to the possible economic and social prospects, and they are aware of
      their disabilities and weaknesses, inability for professional development,
      working and workplace relationships, more difficult money acquisition, etc.

PMID- 18044469
TI  - [Clinical and histopathological characteristics of biopsy-proven renal diseases
      in Croatia].
AB  - There is little data on the spectrum of renal diseases in children in Croatia.
      The Croatian Society for Pediatric Nephrology has established the Registry of
      Biopsy-Proven Renal Diseases in an attempt to address this issue nationwide. Here
      we report preliminary results of a retrospective analysis of clinical and
      histopathological data of 565 children aged < or =17 years presenting to 9
      hospitals in Croatia from 1991 to 2004, in whom kidney biopsy was performed. The
      most common indication for renal biopsy was nephrotic syndrome (39.1%), followed
      by asymptomatic proteinuria/hematuria (22.0%) and acute nephritic syndrome
      (17.0%). All biopsies were analysed by light-, immunofluorescent and electron
      microscopy. The majority of children, 552 out of 565 (92.4%), had
      glomerulonephritis (GN). Tubulointerstitial nephritis was found in 16 (2.8%),
      congenital renal parenchyma anomalies in 14 (2.5%) and vascular disease in 11
      (1.9%) cases. One (0.2%) child had sarcoidosis with nephrocalcinosis. The sample
      was non-diagnostic in 1 (0.2%) case. Among children with GN, primary GN accounted
      for 70.9%, secondary GN for 16.1% and hereditary GN for 13.0% cases. The most
      frequent primary GN forms were focal segmental glomerulosclerosis (FSGS) (24.6%),
      mesangial proliferative glomerulonephritis (MEPGN) (19.2%) and IgA nephropathy
      (18.1%). Acute GN in resolution was found in 11.1% and minimal changes GN in 6.8%
      of cases. Most children with secondary GN had nephritis of Henoch-Schonlein
      purpura (HSP) (54.7%) and nephritis of systemic lupus erythematosus (SLE)
      (40.5%), while among hereditary GN Alport syndrome was most common (80.9%). In
      the group of children with primary GN who presented with nephrotic syndrome, most
      common forms were FSGS (38.5%) and MEPGN (24.0%). Minimal changes GN accounted
      for only 10.9% of cases. IgA nephropathy, primary or related to HSP (20.0%), FSGS
      (16.1%), MEPGN (12.6%) and Alport syndrome (9.7%) were the most common biopsy
      proven renal diseases in Croatian children. The analysis provided data on the
      frequency of histological renal lesions in children in Croatia. The higher
      frequency of FSGS and MEPGN among Croatian children in comparison with other
      countries deserves further evaluation.

PMID- 18044470
TI  - [Is there any connection between angiotensin converting enzyme activity and liver
      cirrhosis of alcoholic genesis?].
AB  - The objective of this study was to assess the serum angiotensin converting enzyme
      (ACE) activity in patients with liver cirrhosis caused by chronic alcohol
      consumption, in order to get better insight into the function of the renin
      angiotensin system. PATIENTS AND METHODS: Serum level of ACE activity was
      measured by Neels spectrophotometry in 35 alcoholic liver cirrhosis patients
      classified according to Child-Pugh-Turcotte criteria and 35 dyspeptic patients
      with any liver disease excluded (control group). RESULTS: Serum values of ACE
      were statistically significantly higher (p < 0.00001) in the group of liver
      cirrhosis patients (x = 250.16 +/- 85.5 nmol) than in the control group (x =
      115.88 +/- 58.19 nmol). The highest levels of ACE were measured in class B group
      of liver cirrhosis patients vs. class A and class B groups (p < 0.013).
      CONCLUSION: It is concluded that liver cirrhosis patients have elevated ACE
      levels, which coud be useful in the diagnosis and follow up of these patients.

PMID- 18044471
TI  - [The relationship of periodontitis and diabetes mellitus].
AB  - Periodontitis is a chronic, dental-plaque induced inflammatory disease of the
      tooth-supporting tissues, resulting in a gradual loss of connective tissue
      attachment and alveolar bone. The interrelationship between diabetes mellitus and
      periodontitis has been studied for many years. At,present, there is strong
      evidence to suggest that the incidence and severity of periodontitis is
      influenced by the presence or absence of diabetes mellitus as well as by the
      degree of diabetes control by patients. Elevated blood glucose levels in poorly
      controlled diabetics result in an increase of protein glycosylation leading to
      amplified formation of so-called Advanced Glycation End products (AGE). AGEs are
      glucose products that have the ability to attract and stimulate inflammatory
      cells to produce inflammatory cytokines, elevating the risk of periodontal
      attachment and/or alveolar bone loss. Gram-negative periodontal infection
      significantly decreases glucose tolerance and can lead, like other types of
      inflammation, to an increase in the severity of diabetes. Thus, diabetes and
      periodontal disease form a system in which periodontitis is aggravated and
      metabolic control of blood glucose levels becomes more difficult. This in turn
      leads to mutual aggravation that results in a self-enforcing catabolic process, a
      vicious circle of inflammation, tissue destruction and insulin resistance.

PMID- 18044472
TI  - [Topical corticosteroids and corticosteroid sparing therapy in psoriasis
      management].
AB  - Psoriasis is a chronic, recurrent, genetically determined, inflammatory
      dermatosis that affects the skin, scalp and joints. Psoriasis is caused by
      various triggers (infections, drugs, physical and emotional factors). It ranges
      in severity from mild to severe, and patients with moderate to severe disease
      suffer significant deterioration in the quality of life. Clinical types of
      psoriasis are psoriasis guttata, nummular psoriasis, plaque, generalized and
      erythrodermic psoriasis. Skin changes affect intertriginous regions (inverse
      psoriasis), and there also are special forms of pustular psoriasis and
      arthropathic psoriasis. The goals of psoriasis treatment are to gain initial and
      rapid control of the disease; to decrease plaque lesions and percentage of body
      surface area involved, to achieve long-term remission; and to minimize adverse
      events. Topical treatment for mild psoriasis includes topical corticosteroids,
      calcipotriene, tazarotene, topical tars, anthralin and keratolytics, and
      immunomodulators (pimecrolimus, tacrolimus). The treatment of moderate to severe
      psoriasis includes systemic therapies such as methotrexate, acitretin,
      cyclosporine, hydroxurea and biologicals. Topical treatment can be effective
      using combination, rotational or sequential regimens for patients with more
      severe disease. The aim of successful treatment of psoriasis is fast control of
      the disease and regression of lesions in a short period, prolonged remission and
      minimal adverse reaction. Local therapy with various topicals is administered for
      mild and localized forms of the disease, with or without phototherapy (UVB).
      Topical corticosteroids are used in a variety of formulations, with a potential
      ranging from superpotent to least potent (class 1-7), which decrease symptoms in
      tne first two weeks of treatment with improvement in subsequent weeks; D3 vitamin
      analog (effective in 6-8 weeks), retinoids (effective in 1-2 weeks), tars (2-4
      weeks), anthralin (2-4 weeks), and keratolytics (most effective in combination
      with corticosteroids. Topical corticosteroids have been the first choice in the
      treatment of and inflammatory dermatoses since 1952 to the present.
      Corticosteroids are effective as monotherapy or in combination for sequential or
      rotational treatment. They are effective in short time, simple for use and
      inexpensive. Psoriasis is a chronic skin disease that requires long-term therapy.
      For patients with mild to moderate form, intermittent corticosteroid therapy is
      the most effective treatment. Every-other-day or weekend-only application may be
      effective in chronic stage. Calcipotriene and tazarotene are more effective in
      combination with corticosteroids in the initial weeks of therapy. Tar
      preparations, anthralin and keratolytics may be used with ultraviolet light and
      corticosteroids. Topical immunomodulators are effective on the face and
      intertriginous psoriatic lesions.

PMID- 18044474
TI  - [Subtenonial application of triamcinolone in neovascular form of senile macular
      degeneration].
AB  - The aim of this prospective study was to investigate the effectiveness of sub
      tenon application of triamcinolone for neovascular age-related macular
      degeneration. The study included 38 eyes (26 patients; 14 women and 12 men, aged
      63 to 82 years) with newly diagnosed subfoveal neovascular age-related macular
      degeneration. Each eye received sub-tenon injection of 0.5 mL suspension of
      triamcinolone-acetonide (20 mg of active substance). Follow up period was 12
      months. After initial application, the injections were repeated on individual
      case, none to five times. Elevated intraocular pressure occurred in five patients
      (seven eyes) and was treated with topical antiglaucomatous therapy. Transient
      ptosis of upper eyelid occurred in one case and completely recovered in two days.
      The mean visual acuity was 0.13 +/- 0.17 on the beginning of the study and 0.22
      +/- 0.22 at the end of the study. Visual acuity improved in 15/38 (39%) eyes,
      remained unchanged in 10/38 (26%) eyes, and worsened in 13/38 (35%) eyes.
      Improvement by three or more lines on Snellen optotype occurred in two cases.
      Comparing our results to those from other authors, sub-tenon application of
      triamcinolone did not prove as effective as when applied intravitreally, but is
      substantially less expensive and easier to perform.

PMID- 18044473
TI  - [Influence of psychoneuroimmunologic factors on patients with malignant skin
      diseases].
AB  - It has been confirmed in research that immune system plays an important role in
      the development of some tumors, for example skin tumors. Different immune
      factors, such as NK cells, T cells, various interleukins and interferon-gamma
      (IFN-gamma), have a significant influence on the process of tumor development and
      appearance of metastasis. On the other hand, many studies have confirmed the
      influence of psychological factors on different aspects of the immune system,
      including the immune cells important in the process of tumor development, and it
      is supposed that psychological factors in this way subsequently influence tumour
      development. It is assumed that endocrine system also has important role in
      process of growth and development of skin tumor. Some studies indicate the
      importance of cortisol, ACTH, and female sex hormones in the occurrence of skin
      tumors, especially malignant melanoma. It has been confirmed in research that
      there is a significant influence of psychological factors on the secretion of
      some hormones, mainly cortisol. Finally, some studies have shown that
      psychological distress may have an impact on two important aspects of
      carcinogenesis: repair of damaged cellular DNA and apoptosis. Many carcinogens
      stimulate tumor development just through destruction of cell DNA, which leads to
      an increased number of abnormal cells, therefore DNA repair acts as one of the
      key mechanisms in the fight against carcinogens. Apoptosis as a process of
      autodestruction of damaged cells also represents an important mechanism of
      antitumor actions. Correlation studies have given important contributions to the
      confirmation of connections between the psychological, immune and endocrine
      factors in tumor development, but intervention studies can give a more detailed
      insight into these connections. Although it was supposed that psychological
      factors could influence the process of tumor development, only lately, with
      improvement in the area of psychoneuroimmunology, new methods and study designs
      have appeared that allow for examination of the process underlying this
      influence.

PMID- 18044475
TI  - [Painful ophthalmoplegia--Tolosa-Hunt syndrome].
AB  - Tolosa Hunt syndrome is a rare disorder caused by nonspecific inflammation in the
      cavernous sinus/superior orbital fissure and/or orbital apex. It is clinically
      characterized by alternating remissions and exacerbations, and manifested as
      diplopia associated with unilateral periorbital hemicranial headache. The
      symptoms include blepharoptosis, which is usually mild if present, bulbomotor
      paresis involving the pupil, and loss of sensation in the area supplied by the
      first division of the trigeminal nerve. Therapy for Tolosa-Hunt syndrome are
      systemic steroids. The course of disease in a 25-year-old man hospitalized for
      painful ophthalmoplegia and diplopia is presented. The history included severe
      pain on rightward eye movement and parabulbarly on the right, considerable defect
      in the area supplied by the first division of the trigeminal nerve, right
      hemicrania, and diplopia on looking to the left, right, upward and downward that
      developed after four days. A month before, the patient was observed at neurology
      department for severe right hemicrania. Current status included severe pain
      parabulbarly on the right, discrete proptosis with mild ptosis on the right eye,
      restricted right eye bulbar motoricity on looking nasally, nasally upward and
      downward, and loss of sensation in the area supplied by the first division of the
      trigeminal nerve. Pupilar motoricity was normal. Upon admission, neuroradiologic
      examination (orbit CT) and brain MR were performed, and therapy with systemic
      corticosteroids was initiated ex iuvantibus, in consultation with a neurologist.
      At 24 hours of corticosteroid therapy, the pain subsided, whereas diplopia
      disappeared almost completely after 5 days, now being only occasionally recorded
      on looking to the left and upward.

PMID- 18044476
TI  - [Value of ultrasound-guided percutaneous renal biopsy in diagnosis of the renal
      diseases].
AB  - Percutaneous renal biopsy (PRB) is an integral part of the clinical practice of
      nephrology. It is a safe and effective tool in the diagnosis of glomerular,
      vascular and tubulointerstitial diseases of the kidney, providing information
      that is invaluable in prognosis and patient management. PRB of native kidneys was
      performed by nephrologists in 249 patients consecutively from May 1997 through
      May 2005 at the Department of Nephrology, Dubrava University Hospital, Zagreb,
      Croatia. The biopsy was done using continuous ultrasound guidance and a 16-gauge
      biopsy needle (Tru-Cut) in an automated gun (Biopty Bard). All biopsies were
      processed for light, immunofluorescence and electron microscopy. We analyzed
      yield of diagnostically useful material and frequency of postbiopsy complication.
      Adequate tissue for histologic diagnosis was obtained in 95% of the procedures.
      The mean glomerular yield was 11.9 glomeruli. The main indications for renal
      biopsy were nephrotic syndrome (33%) hematuria and/or non-nephrotic proteinuria
      (13%) and renal failure (12%). The dominant types of primary glomerulonephritis
      (GN) were focal segmental glomerulosclerosis (FSGS) in 27%, mesangioproliferative
      in 13%, IgA nephropathy in 11%, membranous GN in 11%, membranoproliferative GN in
      5%, crescentic GN--5%, and minimal change disease (MCD) in 3% of cases. The most
      frequent complications were perirenal hematoma (clinically asymptomatic) in 3.6%,
      macrohematuria in 1.2%; bleeding complications requiring blood transfusion and/or
      therapeutic radiologic intervention were not seen, and surgical procedure was
      indicated in one (0.4%) patient. We conclude that real-time ultrasound is a safe,
      accurate method in localizing the kidney for percutaneous renal biopsy and a very
      effective approach for early detection of perirenal hematoma and other potential
      postbiopsy complications. The present data are an important contribution to the
      epidemiology of renal disease, highlighting significant epidemiological
      differences in European countries, particularly a higher incidence of FSGS as a
      proportion of primary GN in our population. This report represents a basis for
      the future Croatian Registry of Renal Biopsies and is intended to serve as a
      source of information for further studies.

PMID- 18044477
TI  - [Combined surgical-orthodontic therapy for compound odontoma].
AB  - Odontogenic tumor is a rare condition in dental medicine that mostly proceeds
      unrecognized until the occurrence of clinical symptoms such as delayed eruption,
      or is incidentally detected on routine x-ray examination. The exact cause is not
      known, however, previous dental trauma and infection have been postulated as the
      potential factors in the development of odontogenic tumor. The earliest possible
      operative extirpation of the tumorous growth is recommended to eliminate
      permanent tooth impaction and to enable normal growth of the teeth. In some
      cases, corticotomy, including complete removal of the bony coat of the tooth, may
      be needed to additionally facilitate and precipitate its eruption. Orthodontic
      therapy is also of great importance in correct alignment of the teeth 'n the
      dental arch as well as in the management of other anomalies that may be
      associated with odontogenic tumor. A patient with compound odontoma is presented,
      along with the course of combined surgical-orthodontic therapy. The patient
      reported previous intrusion trauma that had occurred at the age of 4 years, which
      may have been the potential factor in the development of odontoma. In this case,
      there was a massive odontogenic tumor which had compromised the growth of
      permanent teeth, and the growth impulse was almost at the end since the patient
      was 11 years old and the apexes of the upper incisors were partially closed. The
      first operation included complete removal of the tumorous mass that had
      interrupted spontaneous eruption of the upper permanent incisors. It did not
      result in immediate spontaneous tooth eruption, so an additional operation was
      needed. The objective of the second operative procedure was complete removal of
      the covering bone over the unerupted upper permanent incisors in order to
      eliminate the physical barrier to tooth growth and eruption. The objective of
      fixed orthodontic therapy was full eruption of the partially erupted upper
      incisors. After 16 months, the upper incisors were regularly located in the
      dental arch. In this case, orthodontic therapy had another objective, i.e. to
      ensure rotation of the first upper premolar, to provide space for the upper
      permanent canine eruption and to establish regular intercuspidation after upper
      second premolar hypodontia. In colclusion, combined operative and orthodontic
      therapy can be recommended irrespective of the stage of the impacted tooth
      development because any treatment to precipitate tooth eruption has favorable
      effects. Impacted teeth should always be provided all treatment options for
      faster eruption, as demonstrated in our case where a good clinical result was
      achieved within 2.5 years. The role of regular clinical and x-ray controls for
      assessment of the impacted tooth eruption should also be emphasized.

PMID- 18044478
TI  - [Lipomatosis pelvis].
AB  - The article is a discussion of three cases of lipomatosis in the pelvis and of
      the surgical treatment undertaken in each case. In the first two cases, fatty
      tissue compressed the lower uriunary tract, and in the third, the rectosigmoid
      intestine. In the third case, the patient was also diagnosed as having a
      malignant rectum polyp. In all three cases, the diagnosis by ultrasound,
      intravenous urography and rectoscopy was confirmed by CT. All three patients
      underwent surgery. The first patient was erroneously surgicaly treated in another
      clinic. The operation involved resection of the terminal part of ureters and, on
      the antireflux principle, the reimplantation of ureters into the bladder. The
      patient's condition seriously deteriorated in a short time. In the second case,
      we removed some fatty tissue from the patient's pelvis and performed
      ureteroileocutaneostomy. At present, 14 years since the operation, the patient's
      condition is good. The third patient had malignant rectum polyp, so we removed a
      large part of fatty tissue and performed resection of the anorectum and the
      distal part of the sigmoid colon, together with "anus praeter naturalis
      unipolaris sigmoidalis". The patient's condition, 10 years since the operation,
      is good.

PMID- 18044480
TI  - [Asbestosis--physical examination and symptoms].
AB  - The study included 318 asbestos exposed workers. The aim was to investigate the
      symptomatology and clinical findings over an average period of ten years. We took
      in cosideration quantitative data and analyzed them by statistical methodology of
      univariate and multivariate data analysis and chi2-test. Chest radiography,
      clinical and functional findings were used as a diagnostic tool. The most common
      finding was dyspnea, then cough and chest pain. Clinical symptoms were more
      common in workers exposed to crysotile asbestos than in those exposed to
      crocidolite asbestos. There is strong evidence for association between the
      symptoms and the duration of asbestos exposure. The symptoms were not specific
      for asbestosis. A significant positive correlation was found between physical
      examination and duration of asbestos exposure. Basal rales and pleural rub were
      recorded in 72% of exposed workers.

PMID- 18044479
TI  - [Additive therapy with carboanhydrase inhibitors for open angle glaucoma
      previously treated with timolol 0.5% drops].
AB  - Inhibitors of carboanhydrase (ICA) in the form of dorzolamide 2% drops and
      brinzolamide 1% drops are in use for 8-10 years, with a significant intraocular
      pressure (IOP) lowering effect. The goal of the present study was to obtain
      precise data on the efficacy of local ICA in conjunction with timolol 0.5% drops,
      and to evaluate the incidence of side effects. This was a prospective study that
      lasted 2 years and included 110 patients. Initial IOP values, before therapy with
      ICA, amounted to 19 +/- 8.4 mm Hg in group A and 20.5 +/- mm Hg in group B.
      Although the results obtained demonstrated statistically significant lowering of
      IOP (in group A by 4.5 +/- 2.4 mm Hg, and in group B by 4.6 +/- 2.1 mm Hg) after
      therapy with ICA, the difference between the groups was not found. Dorzolamide
      more frequently caused local side effects like aching, itching and pain in the
      eye. Aditional lowering of lOP in our patients was somewhat greater than reported
      before (4.6:4.3). Side effects (itching, aching, pain) were three times more
      frequent in the group treated with dorzolamide than reported by other authors;
      this difference could be due to patient age, as our patients were mostly elderly
      people and the data are subjective. The results of this study suggested the
      effectiveness of additional local therapy with ICA in patients with open angle
      glaucoma.

PMID- 18044481
TI  - [The disappearance of CD20 positive lymphocytes in the pleural effusion after
      intrapleural application of rituximab].
AB  - A 63 year old woman with non-Hodgkin lymphoma presented with unilateral pleural
      effusion, which when aspirated revealed CD19 and CD20 positive malignant cells.
      Prior to this, the patient had received several lines of chemotherapy (CHOP, VAD,
      FED) with no effect on pleural effusion. Repeated percutaneous drainage
      procedures were unable to control the effusion either. Rituximab was therefore
      instilled in a dose escalating manner via repeated pleurocenteses. Fifty days
      after the application of rituximab, pleural effusion was still present but
      reduced in size. Flow cytometry and immunocytochemistry performed on the same day
      showed CD19 positive cells which were lacking CD20 epitope, which could be
      explained by either engagement or destruction of the CD20 epitope upon
      interaction with rituximab making the detection of the CD20 molecule impossible
      by routine flow cytometry. What is especially interesting is the fact that even
      50 days after the application of rituximab intrapleurally no new CD20 positive
      cells could be found in the pleural effusion by immunochemistry or flow
      cytometry, opening an interesting issue concerning the length of rituximab's
      activity when applied locally. Although our patient had no adverse effects,
      further analysis of rituximab's activity and safety when applied intrapleurally
      is warranted.

PMID- 18044482
TI  - [Mediterranean spotted fever in north Dalmatia: is there a problem?].
AB  - We analyzed clinical and therapeutic characteristics of Mediterranean spotted
      fever (MSF) in north Dalmatia. Analysis was conducted in 93 patients hospitalized
      with MSF at Zadar General Hospital during the 1988-2000 period. The most
      frequently found signs of the disease were high fever (91; 97.8%), maculopapular
      rash (89; 95.7%), headaches (84; 90.3%), arthralgia (75; 80.6%), exhaustion (75;
      80.6%) and nausea (65; 69.9%). Tache noire, as a pathognomonic sign of MSF, was
      found in 22 (23.7%) patients. The most frequently indicated diagnoses were febris
      cum exanthemate (43; 46.2), rickettsiosis suspecta (21; 22.6%) and exanthema
      maculopapulosum (15; 16.1%). Early therapeutic efficiency was achieved by
      doxycycline in 34/43 (79.1%), and by ciprofloxacin in 10/14 (71.4%) treated adult
      patients, and by azithromycin in 7/9 (77.8%) children. The identification of MSF
      endemic rickettsiosis in north Dalmatia, serious clinical forms of the disease
      and the success of early and adequate anti-rickettsial antibiotic therapy are a
      clear warning that our physicians must be very familiar with this disease and
      include this rickettsial disease in differential diagnosis of acute febrile
      diseases accompanied by rash.

PMID- 18044483
TI  - [Gastrointestinal tuberculosis--case report].
AB  - Isolated tuberculosis of gastrointestinal tract is a very rare disease most
      commonly localized in the ileo-cecal region (over 85% of the cases). The main
      object of surgical therapy is intraperitoneal tuberculosis (IP-TB), which leads
      to complications such as bowel obstruction, perforation, fistulation and
      bleeding. Since gastrointestinal tuberculosis can mimic symptoms found in Crohns'
      disease and ileocecal cancer, definitive diagnosis can only be obtained by the
      finding of Mycobacterium tuberculosis in tissue and stool sample as well as by
      positive microbacterial cultivation. A 35 year old female patient was admitted to
      surgical ward with clinical and radiological signs of ileus. From personal
      medical history as well as previous medical documentation we learned that the
      patient had been treated in 1995 for lung and larynx tuberculosis at Jordanovac
      Hospital in Zagreb. After preoperative preparation, the patient underwent surgery
      during which we found numerous stenoses in the region of terminal ileum and
      cecum. Due to the patient's general condition, surgical treatment was performed
      in two acts. In the first we established an L-L ileotransverse anastomosis, and
      in the second we made the resection. The diagnosis was confirmed by histological
      findings of Mycobaterium tuberculosis in stool and tissue samples as well as in
      resection material during operation. The early postoperative period proceeded
      free from complications and after surgical treatment the patient was referred to
      the Klenovnik Special Hospital for Pulmonary Diseases. On follow up 18 months
      after the surgery, there were no signs of gastrointestinal involvement.

PMID- 18044484
TI  - Peak oil or peak emissions?

PMID- 18044485
TI  - The CO2 sponge.

PMID- 18044486
TI  - The fate of fluorotelomer firefighting foams.

PMID- 18044487
TI  - Wind energy on demand.

PMID- 18044488
TI  - Formulating green flame retardants.

PMID- 18044489
TI  - Nonpersuasive communication about matters of greatest urgency: climate change.

PMID- 18044490
TI  - Assessing the relationship between extensive use of organochlorine pesticides and
      cooling trend during the mid-20th century in the southeastern United States.
AB  - In contrast to global warming, temperatures in the southeastern United States
      have exhibited a decreasing trend of up to 1-2 degrees C over the last century.
      We investigated the relationship between this cooling trend and the extensive use
      of organochlorine pesticides--particularly dichloro-diphenyl-trichloroethane
      (DDT) and toxaphene--in the southeastern U.S. from the mid-1940s through the
      1970s. Based on annual use and soil residue estimates, it is shown that
      enthalpies associated with the endothermic evaporation of pesticides from soil
      resulted in surface temperature decreases of up to -0.2 degrees C. This is the
      first study to show the inverse correlation between surface air temperature and
      pesticide use. These findings highlight the potential contribution of the
      extensive use of organochlorine pesticides to changes in the surface air
      temperature, especially in regions of intensive agriculture and pesticide use.

PMID- 18044491
TI  - Allocation of routinely monitored mixing ratios of nitrogen oxides to their
      sources.
AB  - In many urban areas throughout the world, the rising mean and peak levels of
      nitrogen oxides (NOx) are a concern. Road traffic and local industry are usually
      the major NOx sources in urban environments, buttheir relative contributions to
      the spatial distribution of the NOx volumetric mixing ratio is normally unknown.
      This missing piece of information is required for designing effective abatement
      measures to reduce ambient NOx levels. A new method for estimating the shares of
      which traffic and industry contribute to the mean ambient NOx mixing ratios
      observed in urban environments is proposed in this paper. The estimation is based
      on data obtained by routine air pollution monitoring, using a few assumptions
      aboutthe temporal emission patterns of NOx and SO2 in the area of study. A set of
      equations is formulated for the unknown industry and traffic contributions to the
      NOx mixing ratios at each monitoring site. These equations are solved using the
      gradient projection optimization method. The bootstrap technique is used to
      estimate the errors in the process. Spatial maps of the separate shares of
      industry and traffic in the total ambient NOx levels can be obtained where a
      sufficient aerial coverage of stations is available. An application of the method
      to the allocation of NOx mixing ratios to traffic and industrial sources in the
      Haifa Bay area, Israel, is demonstrated. The results are expected to be useful
      for future planning of traffic thoroughfares and industrial development in the
      area.

PMID- 18044492
TI  - Fine-scale spatial variation of persistent organic pollutants in bottlenose
      dolphins (Tursiops truncatus) in Biscayne Bay, Florida.
AB  - Bottlenose dolphins (Tursiops truncatus) are long-term residents and apex
      predators in southeast U.S. estuaries and are vulnerable to bioaccumulation of
      persistent organic pollutants (POPs). Dart biopsy samples were collected from 45
      dolphins in Biscayne Bay (Miami, FL), 34 of which were matched using fin markings
      to a photo identification catalogue. Blubber samples were analyzed for 73
      polychlorinated biphenyl (PCB) congeners, six polybrominated diphenyl ether
      (PBDE) congeners, and organochlorine pesticides including dichloro-diphenyl
      trichloroethane (DDT) and metabolites, chlordanes, and dieldrin. Total PCBs
      (sigma 73PCBs) were present in the highest concentrations and were 5 times higher
      in males with sighting histories in the northern, metropolitan area of Biscayne
      Bay than males with sighting histories in the southern, more rural area
      [geometric mean: 43.3 (95% confidence interval: 28.0-66.9) vs 8.6 (6.3-11.9)
      microg/g wet mass, respectively]. All compound classes had higher concentrations
      in northern animals than southern. The differences in POP concentrations found on
      this small geographic scale demonstrate that differential habitat use can
      strongly influence pollutant concentrations and should be considered when
      interpreting bottlenose dolphin POP data. The PCB concentrations in northern Bay
      dolphins are high as compared to other studies of estuarine dolphins and may
      place these animals at risk of reproductive failure and decreased immune
      function.

PMID- 18044493
TI  - Assessment of the impact of nutrient management practices on nitrate
      contamination in the Abbotsford-Sumas aquifer.
AB  - The impact of recent changes to nutrient management practices in raspberry fields
      on the loading and subsequent transport of nitrate through the vadose zone of the
      Abbotsford-Sumas aquifer is investigated numerically. Previous studies have shown
      that nitrate concentrations in the aquifer have remained relatively stable
      despite a shift in nutrient management practices. Using an estimate of net annual
      available nitrogen in fields that are fertilized using synthetic fertilizer,
      nitrate concentrations as a function of time and depth through the vadose zone
      are simulated from spring to late fall. Results indicate rapid leaching of
      nitrate owing to the permeable nature of the aquifer and suggest that nitrate
      loading to the water table may occur earlier than previously thought, possibly
      due to spring rains. For an average fertilizer application rate of 90 kg of N/ha,
      the simulated nitrate concentration on Oct 1 within the top 1 m of soil is 33 mg
      of N/kg, while the residual soil nitrate measured in late September was 37 mg of
      N/kg. Taking into account the effects of dilution within the saturated zone, the
      simulated peak nitrate concentration is similar to average observed peak
      concentrations in a shallow monitoring well. A solution is offered for estimating
      nitrate concentration at the water table as a function of the rate of synthetic
      fertilizer applied to raspberry fields.

PMID- 18044494
TI  - Current and historical deposition of PBDEs, pesticides, PCBs, and PAHs to Rocky
      Mountain National Park.
AB  - An analytical method was developed for the trace analysis of 98 semivolatile
      organic compounds (SOCs) in remote, high-elevation lake sediment. Sediment cores
      from Lone Pine Lake (west of the Continental Divide) and Mills Lake (east of the
      Continental Divide) in Rocky Mountain National Park, CO, were dated using 210Pb
      and 137Cs and analyzed for polybrominated diphenyl ethers (PBDEs), organochlorine
      pesticides, phosphorothioate pesticides, thiocarbamate pesticides, amide
      herbicides, triazine herbicides, polychlorinated biphenyls (PCBs), and polycyclic
      aromatic hydrocarbons (PAHs) using this method. SOC deposition profiles were
      reconstructed, and deposition half-lives and doubling times were calculated, for
      U.S. historic-use pesticides (HUPs) and current-use pesticides (CUPs) as well as
      PBDEs, PCBs, and PAHs. Sediment records indicate that the deposition of CUPs has
      increased in recent years, while the deposition of HUPs has decreased since U.S.
      restriction, but has not been eliminated. This is likely due to the
      revolatilization of HUPs from regional soils, atmospheric transport, and
      deposition. Differences in the magnitude of SOC sediment fluxes, flux profiles,
      time trends within those profiles, and isomeric ratios suggest that SOC
      deposition in high-elevation ecosystems is dependent on regional upslope wind
      directions and site location with respect to regional sources and topographic
      barriers.

PMID- 18044495
TI  - Use of chemical fingerprinting to establish the presence of spilled crude oil in
      a residential area following Hurricane Katrina, St. Bernard Parish, Louisiana.
AB  - Hurricane Katrina's storm surge displaced and damaged a 250,000 barrel storage
      tank causing a Nigerian crude oil blend (API 36.4 degrees) to be released and
      dispersed into the adjacent evacuated residential area by the retreating
      floodwaters. The subsequent environmental assessment involved sampling and
      chemical fingerprinting of nearly 15,000 wipe and soil samples collected both
      inside and outside of buildings to determine which properties were impacted by
      the spilled crude oil. Tier 1 qualitative analysis of gas chromatograms and Tier
      2 quantitative (revised Nordtest-type) and qualitative (ASTM D5739-type) analysis
      of petroleum biomarkers revealed the extent of crude oil contamination-as well as
      the widespread occurrence of hydrocarbons derived from (i) lubricating,
      hydraulic, and transmission oils, most likely from vehicles in the flooded area,
      and (ii) allochthonous natural organic matter (NOM) from the surrounding bayous.
      Conventional oil spill fingerprinting protocols and two-component mixing models
      (crude oil/lube oil and crude oil/NOM) were used to confirm the presence of the
      spilled crude oil-even when mixed at low concentrations with other hydrocarbon
      sources-as a means to develop and govern a settlement and remedial program with
      the affected property owners.

PMID- 18044496
TI  - Snapping turtles (Chelydra serpentina) as bioindicators in Canadian areas of
      concern in the Great Lakes Basin. 1. Polybrominated diphenyl ethers,
      polychlorinated biphenyls, and organochlorine pesticides in eggs.
AB  - We examined the concentrations and spatial patterns of congeners of PBDEs, PCBs,
      and organochlorine pesticides in snapping turtle (Chelydra serpentina) eggs from
      Areas of Concern (AOCs) on the Canadian shores of Lake Ontario, St. Lawrence
      River, and connecting channels. Eggs from Lyons Creek (Niagara River AOC)
      reflected a local PCB source over a range of 7.5 km (3.2-10.8) from the Welland
      Canal. PCB contamination in eggs declined with increasing distance from the
      Welland Canal, whereas the relative contribution of congeners associated with
      Aroclor 1248/1254 increased with sigma PCB concentrations. Compared to turtle
      eggs from other sites in Lake Erie and Lake Ontario, eggs from Lyons Creek and
      Snye Marsh had PCB congener patterns that reflected a strong contribution from
      Aroclor 1254. PCBs in the eggs were associated with industrial sources and
      reflected the composition of different Aroclor technical mixtures. Organochlorine
      pesticides in eggs tended to be highest at Hamilton Harbour and Bay of Quinte
      AOCs, and were dominated by DDE, sigma chlordane, and mirex. In contrast, PBDE
      congener patterns in turtle eggs resembled PentaBDE technical formulations
      regardless of absolute concentrations or location, and were largely associated
      with urban environments.

PMID- 18044497
TI  - Riverine discharge of perfluorinated carboxylates from the European continent.
AB  - The discharge of C6-C9 perfluorinated carboxylates (PFCAs) from major European
      rivers was studied and employed to assess European emissions of these compounds.
      Water samples were collected close to the mouths of 14 major rivers including the
      Rhine, Danube, Elbe, Oder, Seine, Loire, and Po. PFCA concentrations were
      determined using LC-MS/MS and used together with the mean annual water flow to
      estimate the riverine discharge of the PFCAs. The highest concentration measured
      was 200 ng/L for perfluorooctanoate (PFOA) in the Po River. The Po accounted for
      two-thirds of the total PFOA discharge of all the rivers studied, suggesting a
      major industrial source of PFOA in the Po watershed. All other nonremote rivers
      showed PFOA concentrations in the lower ng/L range, which indicates that widely
      distributed sources are also significant contributors to PFOA emissions in
      Europe. The total discharge of PFOA from the European rivers was estimated to be
      14 tonnes/year, which is in reasonable agreement with reported emissions
      estimates. However, the total riverine discharge of perfluorohexanoate (PFHxA) of
      2.8 tonnes/year estimated in this study was three times greater than the reported
      global emissions estimate, suggesting that there are significant, as yet
      unidentified sources of this compound.

PMID- 18044498
TI  - Deposition and cycling of sulfur controls mercury accumulation in Isle Royale
      fish.
AB  - Mercury contamination of fish is a global problem. Consumption of contaminated
      fish is the primary route of methylmercury exposure in humans and is detrimental
      to health. Newly mandated reductions in anthropogenic mercury emissions aim to
      reduce atmospheric mercury deposition and thus mercury concentrations in fish.
      However, factors other than mercury deposition are important for mercury
      bioaccumulation in fish. In the lakes of Isle Royale, U.S.A., reduced rates of
      sulfate deposition since the Clean Air Act of 1970 have caused mercury
      concentrations in fish to decline to levels that are safe for human consumption,
      even without a discernible decrease in mercury deposition. Therefore, reductions
      in anthropogenic sulfur emissions may provide a synergistic solution to the
      mercury problem in sulfate-limited freshwaters.

PMID- 18044499
TI  - Characteristics of dissolved organic matter in Baltic coastal sea ice:
      allochthonous or autochthonous origins?
AB  - The origin of dissolved organic matter (DOM) within sea ice in coastal waters of
      the Baltic Sea was investigated using parallel factor (PARAFAC) analysis of DOM
      fluorescence. Sea ice DOM had distinctly different fluorescence characteristics
      than that of the underlying humic-rich waters and was dominated by protein-like
      fluorescence signals. PARAFAC analysis identified five fluorescent components,
      all of which were present in both sea ice and water. Three humic components were
      negatively correlated to salinity and concluded to be terrestrially derived
      material. Baltic Sea ice DOM was found to be a mixture of humic material from the
      underlying water column incorporated during ice formation and autochthonous
      material produced by organisms within the ice. Dissolved organic carbon (DOC) and
      nitrogen (DON) concentrations were correlated to the humic fluorescence,
      indicating that the majority of the organic carbon and nitrogen in Baltic Sea ice
      is bound in terrestrial humic material trapped within the ice. This has
      implications for our understanding of sea ice carbon cycling in regions
      influenced by riverine input (e.g., Baltic and Arctic coastal waters), as the
      susceptibility of DOM to degradation and remineralization is largely determined
      by its source.

PMID- 18044500
TI  - Mercury depletion events in the troposphere in mid-latitudes at the Dead Sea,
      Israel.
AB  - The occurrence of mercury depletion events (MDE) in the Polar Regions during the
      spring periods has raised global concern due to the biomagnifications of the
      deposited mercury into the aquatic food chain. However, it now appears that MDE
      is not limited to the Polar Regions and can also occur at mid-latitudes. Diurnal
      cycles of mercury, ozone, and BrO behavior based on short-time resolution
      measurements are presented for the Dead Sea, Israel, for Summer 2006. The results
      show that mercury depletion events occur almost daily, accompanied always by the
      presence of BrO and concurrent ozone destruction. The intensity of the MDE
      corresponded to increasing BrO levels. Mercury depletions of more than 40% were
      observed when BrO levels rose above 60-70 ppt. Based on the present measurements
      and supported bytheoretical considerations, it appears that BrOx (BrO + Br) is
      the primary species responsible for the mercury depletion at the Dead Sea. The
      present study also suggests, especially at low ozone levels, that the Br atom may
      play a major role in conversion of the gaseous elemental mercury to the reactive
      species, HgBr2. The implications of the present study are that even at low BrO
      levels (<10 ppt), mercury depletion may well occur at other mid-latitude sites
      and thus needs to be taken into consideration in the global mercury cycle.

PMID- 18044501
TI  - Relative congener scaling of Polychlorinated dibenzo-p-dioxins and dibenzofurans
      to estimate building fire contributions in air, surface wipes, and dust samples.
AB  - The United States Environmental Protection Agency collected ambient air samples
      in lower Manhattan for about 9 months following the September 11, 2001 World
      Trade Center (WTC) attacks. Measurements were made of a host of airborne
      contaminants including volatile organic compounds, polycyclic aromatic
      hydrocarbons, asbestos, lead, and other contaminants of concern. The present
      study focuses on the broad class of polychlorinated dibenzo-p-dioxins (CDDs) and
      dibenzofurans (CDFs) with specific emphasis on the 17 CDD/CDF congeners that
      exhibit mammalian toxicity. This work is a statistical study comparing the
      internal patterns of CDD/CDFs using data from an unambiguous fire event (WTC) and
      other data sets to help identify their sources. A subset of 29 samples all taken
      between September 16 and October 31, 2001 were treated as a basis set known to be
      heavily impacted by the WTC building fire source. A second basis set was created
      using data from Los Angeles and Oakland, CA as published by the California Air
      Resources Board (CARB) and treated as the archetypical background pattern for
      CDD/CDFs. The CARB data had a congener profile appearing similar to background
      air samples from different locations in America and around the world and in
      different matrices, such as background soils. Such disparate data would normally
      be interpreted with a qualitative pattern recognition based on congener bar
      graphs or other forms of factor or cluster analysis that group similar samples
      together graphically. The procedure developed here employs aspects of those
      statistical methods to develop a single continuous output variable per sample.
      Specifically, a form of variance structure-based cluster analysis is used to
      group congeners within samples to reduce collinearity in the basis sets, new
      variables are created based on these groups, and multivariate regression is
      applied to the reduced variable set to determine a predictive equation. This
      equation predicts a value for an output variable, OPT: the predicted value of OPT
      is near zero (0.00) for a background congener profile and near one (1.00) forthe
      profile characterized by the WTC air profile. Although this empirical method is
      calibrated with relatively small sets of airborne samples, it is shown to be
      generalizable to other WTC, fire source, and background air samples as well as
      other sample matrices including soils, window films and other dust wipes, and
      bulk dusts. However, given the limited data set examined, the method does not
      allow further discrimination between the WTC data and the other fire sources.
      This type of analysis is demonstrated to be useful for complex trace-level data
      sets with limited data and some below-detection entries.

PMID- 18044502
TI  - Phenols and hydroxy-PAHs (arylphenols) as tracers for coal smoke particulate
      matter: source tests and ambient aerosol assessments.
AB  - Source tests were conducted to analyze and characterize diagnostic key tracers
      for emissions from burning of coals with various ranks. Ambient aerosol
      particulate matter was also collected in three areas of China and a background
      area in Corvallis, OR (U.S.) to confirm the presence of tracers specific for coal
      smoke. The results showed a series of aliphatic and aromatic hydrocarbons and
      phenolic compounds, including PAHs and hydroxy-PAHs as the major tracers, as well
      as a significant unresolved complex mixture (UCM) of compounds. The tracers that
      were found characteristic of coal combustion processes included hydroxy-PAHs and
      PAHs. Atmospheric ambient samples from Beijing and Taiyuan, cities where coal is
      burned in northern China, revealed that the hydroxy-PAH tracers were present
      during the wintertime, but not in cities where coal is not commonly used (e.g.,
      Guangzhou, South China). Thus, the mass of hydroxy-PAHs can be apportioned to
      coal smoke and the source strength modeled by summing the proportional contents
      of EC (elemental carbon), PAHs, UCM and alkanes with the hydroxy-PAHs.

PMID- 18044503
TI  - Solubility of hematite revisited: effects of hydration.
AB  - Measured pH and dissolved ferric iron concentration ([Fe(III)diss]) in contact
      with well-characterized hematite indicated an equilibrium with hematite
      immediately after synthesis, but [Fe(III)diss] increased with hydration time to
      be consistent with the predicted solubility of goethite or hydrous ferric oxide
      (HFO), hydrated analogues of hematite. X-ray diffraction did not detect
      structural modification of hematite after 190 days of hydration, but Mossbauer
      spectroscopy detected hydration that penetrated several crystalline layers. When
      the hematite suspension was diluted with water, solids were invariably identified
      as hematite, but [Fe(III)diss] and pH indicated an equilibrium with goethite or
      HFO. This is the first experimental confirmation that the interfacial hydration
      of anhydrous hematite results in higher solubility than predicted by bulk
      thermodynamic properties of hematite. Correspondence of the results with
      previously published measurements and implications for environmental chemistry of
      ferric oxides are also discussed.

PMID- 18044504
TI  - Ternary nucleation as a mechanism for the production of diesel nanoparticles:
      experimental analysis of the volatile and hygroscopic properties of diesel
      exhaust using the volatilization and humidification tandem differential mobility
      analyzer.
AB  - The volatile and hygroscopic properties of diesel nanoparticles were
      simultaneously determined under a range of engine loads using the volatilization
      and humidification tandem differential mobility analyzer (VH-TDMA). Additionally,
      the VH-TDMA was used to measure changes in the hygroscopic behavior of the
      heterogeneously nucleated diesel nanoparticles as one or more semivolatile
      species were removed via thermal evaporation or decomposition. Particles produced
      at high loads exhibited high, dual-step volatility, while those particles
      produced at low loads were less volatile and exhibited continuous volatilization
      curves. The hygroscopic growth factor of the particles was shown to be load
      dependent with high-load particles exhibiting growth factors similar to that of
      ammonium sulfate. At 85% relative humidity, particles produced at moderate loads
      exhibited growth factors of approximately 1.1 while low-load particles were shown
      to be hydrophobic. Growth factors and volatilization temperatures measured for
      high-load particles clearly indicate that ternary nucleation is involved in
      particle formation.

PMID- 18044505
TI  - How does infiltration behavior modify the composition of ambient PM2.5 in indoor
      spaces? An analysis of RIOPA data.
AB  - The indoor environment is an important venue for exposure to fine particulate
      matter (PM2.5) of ambient (outdoor) origin. In this work, paired indoor and
      outdoor PM2.5 species concentrations from three geographically distinct cities
      (Houston, TX, Los Angeles County, CA, and Elizabeth, NJ) were analyzed using
      positive matrix factorization (PMF) and demonstrate that the composition and
      source contributions of ambient PM2.5 are substantially modified by outdoor-to
      indoor transport. Our results suggest that predictions of "indoor PM2.5 of
      ambient origin" are improved when ambient PM2.5 is treated as a combination of
      four distinct particle types with differing infiltration behavior (primary
      combustion, secondary sulfate and organics, secondary nitrate, and mechanically
      generated PM) rather than as a "single internally mixed entity". Study-wide
      average infiltration factors (i.e., fraction of ambient PM2.5 found indoors) for
      Relationship of Indoor, Outdoor, and Personal Air (RIOPA) study homes were 0.51,
      0.78, and 0.04 (consistent with P = 0.6, 0.9, and 0.09; k = 0.2, 0.1, and 0.6 h(
      1)) for PM2.5 associated with primary combustion, secondary formation (excluding
      nitrate), and mechanical generation, respectively. Modification of the
      composition, properties, and source contributions of ambient PM2.5 in indoor
      environments has important implications for exposure mitigation strategies,
      development of health hypotheses, and evaluation of exposure error in
      epidemiological studies that use ambient central-site PM2.5 as a surrogate for
      PM2.5 exposure.

PMID- 18044507
TI  - Identification of the intermediates of in vivo oxidation of 1 ,4-dioxane by
      monooxygenase-containing bacteria.
AB  - 1,4-dioxane is a probable human carcinogen and an emerging water contaminant.
      Monooxygenase-expressing bacteria have been shown to degrade dioxane via growth
      supporting as well as cometabolic mechanisms. In this study, the intermediates of
      dioxane degradation by monooxygenase-expressing bacteria were determined by
      triple quadrupole-mass spectrometry and Fourier transform ion cyclotron resonance
      mass spectrometry. The major intermediates were identified as 2
      hydroxyethoxyacetic acid (HEAA), ethylene glycol, glycolate, and oxalate. Studies
      with uniformly labeled 14C dioxane showed that over 50% of the dioxane was
      mineralized to CO2 by CB1190, while 5% became biomass-associated after 48 h.
      Volatile organic acids and non-volatiles, respectively, accounted for 20 and 11%
      of the radiolabeled carbon. Although strains cometabolizing dioxane exhibited
      limited transformation capacities, nearly half of the initial dioxane was
      recovered as CO2. On the basis of these analytical results, we propose a pathway
      for dioxane oxidation by monooxygenase-expressing cells in which dioxane is first
      converted to 2-hydroxy-1,4-dioxane, which is spontaneously oxidized to HEAA.
      During a second monooxygenation step, HEAA is further hydroxylated, resulting in
      a mixture of dihydroxyethoxyacetic acids with a hydroxyl group at the ortho or
      para position. After cleavage of the second ether bond, small organic molecules
      such as ethylene glycol, glycolate, glyoxalate, and oxalate are progressively
      formed, which are then mineralized to CO2 via common cellular metabolic pathways.
      Bioremediation of dioxane via this pathway is not expected to cause an
      accumulation of toxic compounds in the environment.

PMID- 18044506
TI  - Simulation of the chemical fate and bioavailability of liquid elemental mercury
      drops from gold mining in Amazonian freshwater systems.
AB  - Elemental mercury (Hg(o)) for gold amalgamation is the main process applied by
      artisanal gold miners in South America, leading to important discharges into
      freshwater ecosystems. Through a 28-day experimental approach based on indoor
      microcosms, we simulated the chemical fate and bioavailability of Hg(o) droplets
      in the presence or absence of sediment collected from a typical forest creek that
      is unaffected by gold mining activities. Our results clearly showed significant
      mercury transfers in the water column in both the dissolved gaseous Hg(o) and
      oxidized (Hg(II)) forms, with a marked effect of the presence of sediment. After
      28 days, Hg total (HgT) concentration in the water column was 25 times higher in
      sediment-free units (108 +/- 17 vs. 4 +/- 0.4 nM). Methylmercury (MeHg)
      determinations in the dissolved fraction showed a significant increase only in
      the presence of sediment after 7 and 14 days. Zebrafish (Danio rerio) were used
      as indicators for mercury bioavailability. The HgT determinations in four organs
      revealed significant accumulation levels as early as 7 days exposure, with marked
      differences in favor of fish collected from the sediment-free units. Significant
      MeHg increases were observed in the four organs only when sediment was present.
      Genomic tools applied to estimate sulfate-reducing bacteria communities showed
      mercury impacts on their diversity and distribution in the different compartments
      (water, sediment, biofilm, fish gut).

PMID- 18044508
TI  - Influence of dissolved organic matter and Fe(II) on the abiotic reduction of
      pentachloronitrobenzene.
AB  - Nitroaromatic pesticides (NAPs) are hydrophobic contaminants that can accumulate
      in sediments by the deposition of suspended solids from surface waters. Fe(II)
      and dissolved organic matter (DOM), present in suboxic and anoxic zones of
      freshwater sediments, can transform NAPs in natural systems. We studied the
      reduction of pentachloronitrobenzene (PCNB) to pentachloroaniline (PCA) in
      controlled studies using Fe(II) and surface water DOM isolates from Pony Lake,
      Antarctica, and Suwannee River, GA, in unfiltered and 0.45 microm filtered
      solutions. We observed rapid reduction of PCNB to PCA in the presence of Fe(II)
      and DOM (t(1/2) approximately = 30 min to 4 h) and very limited reduction in DOM
      only systems. DOM in unfiltered systems inhibited iron colloid formation and
      potentially limited the formation of reactive Fe(ll)-iron colloid surface
      complexes, causing reductive transformation in Fe(II)-DOM media to be slower in
      some cases relative to Fe(ll)-only controls. Conversely, in 0.45 microm filtered
      solutions, PCNB reduction in Fe(III)-DOM media was faster than the Fe(II)-only
      controls, suggesting that DOM enhances the reductive capacity of Fe(ll) in the
      absence of iron colloids. This work shows that DOM may significantly affect the
      reactivity of Fe(ll) toward NAPs under suboxic and anoxic conditions in natural
      wetland sediments.

PMID- 18044509
TI  - Speciation-dependent microbial reduction of uranium within iron-coated sands.
AB  - Transport of uranium within surface and subsurface environments is predicated
      largely on its redox state. Uranyl reduction may transpire through either biotic
      (enzymatic) or abiotic pathways; in either case, reduction of U(VI) to U(IV)
      results in the formation of sparingly soluble UO2 precipitates. Biological
      reduction of U(VI), while demonstrated as prolific under both laboratory and
      field conditions, is influenced by competing electron acceptors (such as nitrate,
      manganese oxides, or iron oxides) and uranyl speciation. Formation of Ca-UO2-CO3
      ternary complexes, often the predominate uranyl species in carbonate-bearing
      soils and sediments, decreases the rate of dissimilatory U(VI) reduction. The
      combined influence of uranyl speciation within a mineralogical matrix comparable
      to natural environments and under hydrodynamic conditions, however, remains
      unresolved. We therefore examined uranyl reduction by Shewanella putrefaciens
      within packed mineral columns of ferrihydrite-coated quartz sand under conditions
      conducive or nonconducive to Ca-UO2-CO3 species formation. The results are
      dramatic. In the absence of Ca, where uranyl carbonato complexes dominate, U(VI)
      reduction transpires and consumes all of the U(VI) within the influent solution
      (0.166 mM) over the first 2.5 cm of the flow field for the entirety of the 54 d
      experiment. Over 2 g of U is deposited during this reaction period, and despite
      ferrihydrite being a competitive electron acceptor, uranium reduction appears
      unabated for the duration of our experiments. By contrast, in columns with 4 mM
      Ca in the influent solution (0.166 mM uranyl), reduction (enzymatic or surface
      bound Fe(III) mediated) appears absent and breakthrough occurs within 18 d (at a
      flow rate of 3 pore volumes per day). Uranyl speciation, and in particular the
      formation of ternary Ca-UO2-CO3 complexes, has a profound impact on U(VI)
      reduction and thus transport within anaerobic systems.

PMID- 18044510
TI  - Dissipation and transport of veterinary sulfonamide antibiotics after manure
      application to grassland in a small catchment.
AB  - The heavy use of veterinary antibiotics in modern animal production causes
      concern about risks of spreading antibiotic resistance after manure applications
      to agricultural fields. We report on a field study aiming at elucidating the fate
      of sulfonamide (SA) antibiotics in grassland soils and their transport to surface
      water. Two controlled manure applications were carried out under different
      weather conditions. After both applications, the SA concentrations in pore water
      and the total soil content declined rapidly. This stage of fast decline was
      followed by a second one during which the SA were rather persistent. More than
      15% of the SAs applied were still present in the soil 3 months after application,
      always exceeding 100 microg/kg topsoil. The apparent SA sorption increased
      strongly with time. Accordingly, the risk for SA losses to water bodies decreased
      within 2 weeks to very low values. In contrast to SA concentrations in the soil,
      losses to the brook were strongly influenced by the weather conditions after the
      two manure applications. The overall losses were 15 times larger (about 0.5% of
      applied SA) during the wet conditions of May 2003 compared to the dry conditions
      following the first application (March 2003).

PMID- 18044511
TI  - Mercury emission to the atmosphere from experimental manipulation of DOC and UVR
      in mesoscale field chambers in a freshwater lake.
AB  - Mesocosm experiments in an optically transparent lake allow the manipulation of
      both dissolved organic carbon (DOC) and incident ultraviolet radiation (UVR) in
      order to study mercury reduction and emission processes. In the absence of UVR
      and the presence of visible light, mercury emission is very low (approximately0.3
      ng/m2/h). When UVR is permitted in the mesocosm chambers, mercury emission
      increases, with emission rates ranging from 0.3 to 2.5 ng/m2/h. At concentrations
      between 1.5 and 2.5 mg/L DOC, mercury emission does not appear to depend on
      either the concentration or the optical properties of the DOC. In particular, the
      addition of 1.0 mg/L DOC from a nearby wetland to a photobleached mesocosm did
      not increase the emission of mercury. The similarities between mercury emission
      from highly photobleached 1.5 mg/L DOC and from terrestrially enriched 2.5 mg/L
      DOC suggest that the moieties responsible for mercury reduction are far in excess
      of that needed for mercury reduction. Using the measured flux rate of mercury
      from the water surface, we calculated a dissolved gaseous mercury (DGM)
      concentration thatwould need to be present to drive the emissive flux. The
      buildup of DGM was used to approximate a kinetic rate constant for the net
      mercury reduction in this system of approximately 0.17 h(-1), which is consistent
      with existing published values.

PMID- 18044512
TI  - Bioconcentration factor hydrophobicity cutoff: an artificial phenomenon
      reconstructed.
AB  - The debate on whether highly hydrophobic organic chemicals (with log Kow > 5-6)
      bioconcentrate less than may be expected from their hydrophobicity is still not
      settled. The often-observed hydrophobicity "cutoff" might either be explained by
      artifacts occurring during bioconcentration factor (BCF) measurements or by a
      true mechanism, i.e., reduced uptake of larger molecules due to decreased
      membrane permeation. In this paper, we advocate there is no hydrophobicity
      cutoff, at least not for compounds with log Kow of up to 7.5. Data are presented
      on the uptake of polycyclic aromatic hydrocarbons (PAHs) in the aquatic worm
      Lumbriculus variegatus. For this combination of chemicals/organism, BCFs were
      measured using several approaches, including traditional batch uptake kinetics
      measurements and alternative ones, involving solid-phase microextraction (SPME),
      polyoxymethylene solid-phase extraction (POM-SPE), field exposures, and the
      substitution of living worms by dead worm material or liposomes. A hydrophobicity
      cutoff was observed at two levels during the traditional approach only, whereas
      for the other approaches it was absent. The data were used to demonstrate the
      presence and impact of artifacts due to so-called "third phase effects" and
      nonequilibrium conditions that can obscure "true uptake". The experiments suggest
      that previously observed cutoff effects can be ascribed to artifacts, and that
      current risk assessment (often incorporating a BCF cutoff) as well as BCF
      measurement techniques of very hydrophobic chemicals should be revised.

PMID- 18044514
TI  - Evidence for elevated production of methylmercury in salt marshes.
AB  - Depth variations of total mercury (Hg) and methylmercury (MeHg) concentrations
      were obtained in cores from nonvegetated sediments, sediments colonized by
      Sarcocornia fruticosa, Halimione portulacoides, and Spartina maritima and below
      ground biomass in three Portuguese estuaries. Similar analyses were also
      performed on the above-ground plant tissues. Concentrations in below-ground
      biomass exceeded up to 9 (Hg) and 44 (MeHg) times the levels in sediments.
      Mercury and MeHg in below-ground biomass were up to 400 (Hg) and 4700 (MeHg)
      times higher than those found in above-ground parts, indicating a weak upward
      translocation. Methylmercury in colonized sediments reached 18% of the total Hg,
      which was 70 times above the maximum values found in nonvegetated sediments.
      Concentrations of MeHg in vegetated sediments were not related to plant type but
      were linearly proportional to the total mercury levels. The analysis of below
      ground biomass at high depth resolution (2 cm) provided evidence that Hg and MeHg
      were elevated. The higher enrichment factors were found where the shifting of
      redox conditions suggested high microbial activity. Mercury and MeHg in below
      ground tissues were a function of total levels in sediments and again were not
      plant-specific. These results suggest that the bioremediation of mercury
      contaminated sediments is likely to increase the formation of methylmercury.

PMID- 18044513
TI  - Evidence for a radical mechanism of the dechlorination of chlorinated propenes
      mediated by the tetrachloroethene reductive dehalogenase of Sulfurospirillum
      muftivorans.
AB  - The reductive dehalogenation of chlorinated propenes was studied with the
      tetrachloroethene reductive dehalogenase purified from Sulfurospirillum
      multivorans to obtain indications for a radical mechanism of this reaction. When
      reduced methyl viologen (MV), which is a radical cation, was applied as electron
      donor for the reduction of different chloropropenes, a significant part of MV
      could not be rereduced with Ti(III) citrate, indicating that a part of the MV was
      consumed in a side reaction. Mass spectrometric analysis of assays with MV as
      electron donor revealed the formation of side products, the masses of which might
      account for the formation of adducts from a chloropropenyl radical and reduced
      methyl viologen. With Ti(III) citrate as sole electron donor, 2,3-dichloropropene
      was reduced and as a side product, 2,5-dichloro-1,5-hexadiene was formed
      demonstrating that the reductive dechlorination of 2,3-dichloropropene proceeds
      via a radical reaction mechanism. The results support different dehalogenation
      mechanisms forthe reductive dechlorination of chloropropenes and halogenated
      ethenes.

PMID- 18044515
TI  - Prevalence of multi-antimicrobial-agent resistant, shiga toxin and enterotoxin
      producing Escherichia coli in surface waters of river Ganga.
AB  - The consumption of polluted surface water for domestic and recreational purposes
      by large populations in developing nations is a major cause of diarrheal disease
      related mortality. The river Ganga and its tributaries meet 40% of the water
      requirement for drinking and irrigation in India. In this study, Escherichia coli
      isolates (n=75) of the river Ganga water were investigated for resistance to
      antimicrobial agents (n=15) and virulence genes specific to shiga toxin (STEC)
      and enterotoxin producing E. coli (ETEC). E. coli isolates from the river Ganga
      water exhibit resistance to multiple antimicrobial agents. The distribution of
      antimicrobial agent resistance in E. colivaries significantly (chi2: 81.28 at df
      = 24, p < 0.001) between the sites. Both stx1 and stx2 genes were present in
      82.3% of STEC (n=17) while remaining isolates possess either stxl (11.8%) or stx2
      (5.9%). The presence of eaeA, hlyA, and chuA genes was observed in 70.6, 88.2,
      and 58.8% of STEC, respectively. Both LT1 and ST1 genes were positive in 66.7% of
      ETEC (n=15) while 33.3% of isolates harbor only LT1 gene. The prevalence of multi
      antimicrobial-agent resistant E. coli in the river Ganga water poses increased
      risk of infections in the human population.

PMID- 18044516
TI  - Atmospheric chemistry of 2-ethoxy-3,3,4,4,5-pentafluorotetrahydro-2,5-bis[1,2,2,2
      tetrafluoro-1-(trifluoromethyl)ethyl]-furan: kinetics, mechanisms, and products
      of Cl atom and OH radical initiated oxidation.
AB  - Smog chamber/FTIR techniques were used to study the atmospheric chemistry of the
      title compound which we refer to as RfOC2H5. Rate constants of k(Cl + RfOC2H5) =
      (2.70 +/- 0.36) x 10(-12), k(OH + RfOC2H5) = (5.93 +/- 0.85) x 10(-14), and k(Cl
      + RfOCHO) = (1.34 +/- 0.20) x 10(-14) cm3 molecule(-1') s(-1) were measured in
      700 Torr of N2, or air, diluent at 294 +/- 1 K. From the value of k(OH + RfOC2H5)
      the atmospheric lifetime of RfOC2H5 was estimated to be 1 year. Two competing
      loss mechanisms for RfOCH(O*)CH3 radicals were identified in 700 Torr of N2/O2
      diluent at 294 +/- 1 K; decomposition via C-C bond scission giving a formate
      (RfOCHO), or reaction with 02 giving an acetate (RfOC(O)CH3). In 700 Torr of
      N2/O2 diluent at 294 +/- 1 K the rate constant ratio k(O2)/k(diss) = (1.26 +/-
      0.74) x 10(-19) cm3 molecule(-1). The OH radical initiated atmospheric oxidation
      of RfOC2H5 gives Rf0CHO and RfOC(O)CH3 as major products. RfOC2H5 has a global
      warming potential of approximately 55 for a 100 year horizon. The results are
      discussed with respect to the atmospheric chemistry and environmental impact of
      RfOC2H5.

PMID- 18044517
TI  - Transport and retention of colloidal aggregates of C60 in porous media: effects
      of organic macromolecules, ionic composition, and preparation method.
AB  - The physical-chemical behavior of the fullerene C60 in environmental and
      physiological media is of interest for understanding the potential transport,
      exposure, and impacts of these materials on organisms and ecosystems. We
      considerthe role of electrolyte composition and concentration, the effect of
      organic macromolecules, and the mode of preparation of colloidal aggregates of
      C60 (nC60) on the deposition of these colloids in a porous medium such as a
      groundwater aquifer or a water treatment filter. Results for nC60 deposition are
      qualitatively consistent with trends anticipated by theory. Deposition was found
      to increase with increasing ionic strength, the presence of polysaccharide-type
      organic matter, and lower Darcy velocities. Factors that will tend to decrease
      the retention of these materials in porous media include a low ionic strength and
      the presence of humic-like substances, while the ionic strengths typical of many
      natural waters and the presence polysaccharide-based natural organic matter, as
      may be produced by algae or bacteria, will tend to favor deposition and reduced
      potential for exposure. Variability in the method of preparing colloidal
      aggregates of fullerenes was observed to yield significant differences in nC60
      properties and transport behavior.

PMID- 18044518
TI  - Secondary organic aerosol formation from the photooxidation of p- and o-xylene.
AB  - The formation of secondary organic aerosol (SOA) from the photooxidation of
      xylene isomers (m-, p-, and o-xylenes) has been extensively investigated. The
      dependence of SOA aerosol formation on the structure of xylene isomers in the
      presence of NO was confirmed. Generally, SOA formation of p-xylene was less than
      that of m- and o-xylenes. This discrepancy varies significantly with initial NOx
      levels. In a NOx-free environment, the difference of aerosol formation between o-
      and p-xylenes becomes insignificant. Several chemical pathways for the SOA
      dependence on structure and NOx are explored, with the experimental findings
      indicating that organic peroxides may be a major key to explaining SOA formation
      from aromatic hydrocarbons.

PMID- 18044519
TI  - Secondary organic aerosol formation from m-xylene in the absence of NOx.
AB  - Formation of secondary organic aerosol (SOA) from m-xylene photoxidation in the
      absence of NOx was investigated in a series of smog chamber experiments.
      Experiments were performed in dry air and in the absence of seed aerosol with
      H2O2 photolysis providing a stable hydroxyl radical (OH radical) source. SOA
      formation from this study is exceptionally higher than experiments with existence
      of NOx. The experiments with elevated HO2 levels indicate that organic
      hydroperoxide compounds should contribute to SOA formation. Nitrogen oxide (NO)
      is shown to reduce aerosol formation; the constant aerosol formation rate
      obtained before addition of NO and after consumption of NO strongly suggests that
      aerosol formation is mainlythrough reactions with OH and HO2 radicals. In
      addition, a density of 1.40 +/- 0.1 g cm(-3) for the SOA from the photooxidation
      of m-xylene in the absence of NOx has been measured, which is significantly
      higherthan the currently used unit density.

PMID- 18044520
TI  - Influence of sources on plutonium mobility and oxidation state transformations in
      vadose zone sediments.
AB  - Well-defined solid sources of Pu(III) (PuCl3), Pu(IV) (Pu (NO3)4 and Pu (C2O4)2),
      and Pu(VI) (Pu02(NO3)2) were placed in lysimeters containing vadose zone
      sediments and exposed to natural weather conditions for 2 or 11 years. The
      objective of this study was to measure the release rate of Pu and the changes in
      the Pu oxidation states from these Pu sources with the intent to develop a
      reactive transport model source-term. Pu(III) and Pu(IV) sources had identical Pu
      concentration depth profiles and similar Pu release rates. Source release data
      indicate that PuIV(C2O4)2 was the least mobile, whereas Pu(VI)O2(NO3)2 was the
      most mobile. Synchrotron X-ray fluorescence (SXRF) revealed that Pu was very
      unevenly distributed on the sediment and Mn concentrations were too low (630 mg
      kg(-1)) and perhaps of the wrong mineralogy to influence Pu distribution. The
      high stability of sorbed Pu(IV) is proposed to be due to the formation of a
      stable hydrolyzed Pu(IV) surface species. Plutonium X-ray absorption near-edge
      spectroscopy (XANES) analysis conducted on sediment recovered at the end of the
      studyfrom the Pu(IV)(NO3)4- and Pu(III)(III)Cl3-amended lysimeters contained
      essentially identical Pu distributions: approximately 37% Pu(III), 67% Pu(IV), 0%
      Pu(V), and 0% Pu(VI). These results were similar to those using a wet chemistry
      Pu oxidation state assay, except the latter method did not detect any Pu(III)
      present on the sediment but instead indicated that 93-98% of the Pu existed as
      Pu(IV). This discrepancy was likely attributable to incomplete extraction of
      sediment Pu(III) by the wet chemistry method. Although Pu has been known to exist
      in the +3 oxidation state under microbially induced reducing conditions for
      decades, to our knowledge, this is the first observation of steady-state Pu(III)
      in association with natural sediments. On the basis of thermodynamic
      considerations, Pu(III) has a wide potential distribution, especially in acidic
      environments, and as such may warrant further investigation.

PMID- 18044521
TI  - Unexpected response of high Alpine Lake waters to climate warming.
AB  - Over the past two decades, we have observed a substantial rise in solute
      concentration at two remote high mountain lakes in catchments of metamorphic
      rocks in the European Alps. At Rasass See, the electrical conductivity increased
      18-fold. Unexpectedly high nickel concentrations at Rasass See, which exceeded
      the limit in drinking water by more than 1 order of magnitude, cannot be related
      to catchment geology. We attribute these changes in lake water quality to solute
      release from the ice of an active rock glacier in the catchment as a response to
      climate warming. Similar processes occurred at the higher elevation lake
      Schwarzsee ob Solden, where electrical conductivity has risen 3-fold during the
      past two decades.

PMID- 18044522
TI  - Enhanced copper release from pipes by alternating stagnation and flow events.
AB  - Traditional studies of copper release in plumbing systems assume that the water
      extracted from a pipe follows a plug-type flow and that the pipe surface does not
      interact with the bulk water under flow conditions. We characterized actual
      stagnation-flushing cycles in a household pipe undergoing corrosion in the
      presence of a microbial biofilm. The mass of copper released in 10 experiments
      was on average 8 times the value estimated by using the plug-flow assumption. The
      experimental copper release pattern was explained by an advection-diffusion model
      only if a high copper concentration occurs near the pipe surface after
      stagnation. Microscopic examination of the pipe surface showed a complex
      assemblage of biotic and abiotic features. X-ray diffraction analyses identified
      only malachite, while X-ray absorption spectroscopy also revealed cupric
      hydroxide and cuprite. These results indicate that the surface serves as a
      storage compartment of labile copper that may be released under flow conditions.
      Thus, the diffusive transport from the pipe surface to the bulk during stagnation
      is not the only control of the flux of copper to the tap water when porous
      reactive microstructures cover the pipe. Our results highlight the need for
      models that consider the interaction between the hydrodynamics, chemistry, and
      structure at the solid-water interface to predict the release of corrosion
      byproducts into drinking water.

PMID- 18044523
TI  - Effect of surface chemistry of Fe-Ni nanoparticles on mechanistic pathways of azo
      dye degradation.
AB  - The degradation of Orange G, a monoazo dye, in aqueous solutions was investigated
      using as-synthesized and stored Fe-Ni bimetallic nanoparticles. Batch experiments
      with a nanocatalyst loading of 3 g/L showed complete dye degradation (150 mg/L)
      after 10 min of reaction time. HPLC-MS analysis of the degradation products
      showed that as-synthesized nanoparticles reductively cleaved the azo linkage to
      produce aniline as the major degradation product. However, 1-year-stored
      nanoparticles showed an oxidative degradation of Orange G through a hydroxyl
      radical induced coupling of parent and/or product molecules. XPS analysis in
      corroboration with HPLC-MS data showed that the surface chemistry between Fe and
      Ni in as-synthesized and stored nanoparticles play a crucial role in directing
      the mode of degradation. Reductive dye degradation using as-synthesized
      nanoparticles proceeded through hydride transfer from nickel, whereas formation
      of a Fe2+ -Ni(0) galvanic cell in stored nanoparticles generated hydroxyl
      radicals from water in a nonFenton type reaction. The latter were responsible for
      the generation of radical centers on the dye molecule, which led to a coupling
      mediated oxidative degradation of Orange G. The generation of hydroxyl radicals
      is further substantiated with radical quenching experiments using ascorbic acid
      indicating that stored nanoparticles degrade Orange G through a predominantly
      oxidative mechanism. HPLC-MS and XPS analysis of dye degradation using as
      synthesized nanoparticles exposed to air and water confirmed that the reductive
      or oxidative degradation capability of Fe-Ni nanoparticles is decided by the time
      and type of catalyst aging process.

PMID- 18044524
TI  - Including spatial variability in Monte Carlo simulations of pesticide leaching.
AB  - A methodology is developed to quantify the uncertainty in a pesticide leaching
      assessment arising from the spatial variability of non-georeferenced parameters.
      A Monte Carlo analysis of atrazine leaching is performed in the Dyle river
      catchment (Belgium) with pesticide half-life (DT50) and topsoil organic matter
      (OM) content as uncertain input parameters. Atrazine DT50 is taken as a non
      georeferenced parameter, so that DT50 values sampled from the input distribution
      are randomly allocated in the study area for every simulation. Organic matter
      content is a georeferenced parameter, so that a fixed uncertainty distribution is
      given at each location. Spatially variable DT50 values are found to have a
      significant influence on the amount of simulated leaching. In the stochastic
      simulation, concentrations exist above the regulatory level of 0.1 microg L(-1),
      but virtually no leaching occurs in the deterministic simulation. It is axiomatic
      that substance parameters (DT50, sorption coefficient, etc.) are spatially
      variable, but pesticide registration procedures currently ignore this fact.
      Including this spatial variability in future registration policies would have
      significant consequences on the amount and pattern of leaching simulated,
      especially if risk assessments are implemented in a spatially distributed way.

PMID- 18044525
TI  - Cost effectiveness of regulation-compliant filtration to control sediment and
      metal pollution in urban runoff.
AB  - The implementation of Total Maximum Daily Load (TMDL) to control urban runoff
      presents major structural and managerial challenges for cities. We developed a
      decision support system (DSS) for TMDL compliance at the city level to solve for
      a phased, least-cost strategy toward meeting four TMDLs using stormwater
      filtration. Based on a case-study city, we modeled wet weather flows and
      associated discharge of Total Suspended Sediment (TSS), cadmium, copper, and zinc
      to receiving waters by coupling U.S. EPA's Storm Water Management Model (SWMM v.
      5.0) with the geographic dataset of the urban drainage network. We linked a mixed
      integer linear programming algorithm to the watershed model for deriving cost
      effective selection and placement of curb inlet filters to meet mass- and
      concentration-based TMDL requirements. The least cost solution for meeting the
      city's TMDL waste load allocations for TSS (73.9% reduction), Cd (50.6%
      reduction), Cu (30.0% reduction), and Zn (55.7% reduction) would require 1071
      filter inserts at a cost of $1.7 million. In contrast, random placement of 1071
      filters or uniform placement of 1266 filters is effective only for TSS and would
      cost $4.0 million and $4.8 million, respectively. Our results demonstrate the
      increases in cost-effectiveness of using an optimization-based DSS for urban
      watershed management.

PMID- 18044526
TI  - Synthesis of octabrominated diphenyl ethers from aminodiphenyl ethers.
AB  - Polybrominated diphenyl ethers (PBDEs) are additive brominated flame retardants
      (BFRs), which have become widespread pollutants in abiotic and biotic
      environments including man. Tetra- to hexaBDEs and decaBDE are the most common
      environmental PBDE contaminants. Congeners of octabromodiphenyl ethers (octaBDEs)
      originate from used industrial OctaBDE mixtures and from transformation products
      of the high-volume industrial BFR mixture "DecaBDE", which most exclusively
      consists of perbrominated diphenyl ether (BDE-209). The objective of the present
      work was to develop methods for the synthesis of authentic octaBDE congeners in
      order to make them available as standards for analytical, toxicological, and
      stability studies, as well as studies concerning physical-chemical properties.
      The syntheses of six octaBDEs, 2,2',3,3',4,4',5,5'-octabromodiphenyl ether (BDE
      194), 2,2',3,3',4,4',5,6'-octabromodiphenyl ether (BDE-196), 2,2',3,3',4,5,5',6
      octabromodiphenyl ether (BDE-198), 2,2',3,3',4,5',6,6'-octabromodiphenyl ether
      (BDE-201), 2,2',3,3',5,5',6,6'-octabromodiphenyl ether (BDE-202), and
      2,2',3,4,4',5,6,6'-octabromdipheny ether (BDE-204), are described, of which BDE
      204 was prepared via two different pathways. Syntheses of BDE-198, BDE-201, BDE
      202, and BDE-204 are based on octabromination of mono- or diaminodiphenyl ethers
      followed by diazotization and reduction of the amino group(s). BDE-194 and BDE
      196 were prepared by bromination of 3,3',4,4',5,5'-hexabromodiphenyl ether (BDE
      169) and 2,3,3',4,4',5',6-heptabromodiphenyl ether (BDE-191), respectively, and
      BDE-169 and BDE-191 were prepared from 4,4'-diaminodiphenyl ether and 3,4'
      diamiodiphenyl ether, respectively. The synthesized PBDE congeners are described
      by 1H NMR, 13C NMR, electron ionization mass spectra, and their melting points.

PMID- 18044527
TI  - Size distribution of trace organic species emitted from light-duty gasoline
      vehicles.
AB  - Size distributions for particulate hopanes+steranes and nonvolatile polycyclic
      aromatic hydrocarbons (PAHs) emitted from five classes of light-duty gasoline
      powered vehicles were measured using the federal test procedure (FTP), unified
      cycle (UC), and correction cycle (CC) driving cycles. 17alpha(H)-21beta(H)-29
      norhopane, 17alpha(H)-21beta(H)-hopane, alpha beta beta-20R-stigmastane, and
      alpha beta beta-20S-stigmastane were highly correlated and behaved consistently
      across sampling methods. Coronene and benzo[ghi]perylene were the most ubiquitous
      heavy PAHs detected in the vehicle exhaust. The emission rates of hopanes,
      steranes, and PAHs contained in particles with aerodynamic diameters of less than
      1.8 ,m varied by 2 orders of magnitude between the lowest- and highest-emitting
      vehicle classes. Hopane+sterane size distributions emitted from vehicles without
      an operating catalyst (including "cold-start" emissions from catalyst-equipped
      vehicles) were bimodal with one mode between 0.10 and 0.18 microm and the second
      mode >0.32 microm particle diameter. Hopane+sterane emissions released from
      vehicles with a catalyst at operating temperature had a single mode between 0.1
      and 0.18 microm diameter. Hopane+sterane emissions from visibly smoking vehicles
      had a single mode between 0.18 and 0.32 microm diameter. Heavy PAH size
      distributions for all vehicle classes consistently had a single mode between 0.10
      and 0.18 microm particle diameter (0.1-0.32 microm diameter for smoking
      vehicles). The geometric standard deviations for PAH size distributions were
      generally smaller than the corresponding hopane+sterane distributions. These
      trends suggest that hopanes+steranes and heavy PAHs act as tracers for separate
      processes of particulate organic carbon formation. PAH and hopane+sterane
      emissions shifted to smaller sizes during the more aggressive UC and CC driving
      cycles relative to the FTP. The fraction of PAH and hopane+sterane emissions in
      the ultrafine (Dp < 0.1 microm) range more than doubled during "warm-start" UC
      and CC cycles vs the FTP cycle. The enhancement of ultrafine PAHs during "cold
      start" UC driving cycles was less pronounced.

PMID- 18044528
TI  - Predicting PAH bioaccumulation and toxicity in earthworms exposed to manufactured
      gas plant soils with solid-phase microextraction.
AB  - Soils from former manufactured gas plant (MGP) sites are often heavily
      contaminated with polycyclic aromatic hydrocarbons (PAHs). Current risk
      assessment methods that rely on total PAH concentrations likely overstate adverse
      effects of such soils since bioavailability is ignored. In this study, solid
      phase microextraction (SPME) was applied to estimate bioavailable PAH
      concentrations and toxicity in earthworms exposed to 15 MGP soils. In addition,
      PAH sorption to all soils (K0o values) was determined. The results showed a
      several orders of magnitude variation in Koc values, demonstrating that generic
      organic carbon-normalized sorption coefficients will typically be
      overconservative at MGP sites. SPME-predicted bioaccumulation generally was
      within a factor of 10 of measured bioaccumulation (in earthworm bioassays), in
      contrast to current risk assessment model estimates that overpredicted
      bioaccumulation 10-10 000 times. Furthermore, on the basis of estimated total
      body residues of narcotic PAHs, SPME correctly predicted worm mortality observed
      during bioassays in the majority of cases. For MGP sites where current risk
      assessment procedures indicate concerns, SPME thus provides a useful tool for
      performing a refined, site-specific assessment.

PMID- 18044529
TI  - A protocol to assess the enzymatic release of dissolved organic phosphorus
      species in waters under environmentally relevant conditions.
AB  - A protocol to assess the potential release of dissolved reactive phosphorus (DRP)
      by enzymatic hydrolysis of dissolved organic phosphorus (DOP) in waters (sediment
      porewater and sewage liquors in this study) under environmental conditions is
      presented. This protocol enables the quantification of different classes of DOP
      compounds using a variety of phosphatase enzymes, i.e., alkaline phosphatase,
      phosphodiesterase, and phytase. All experiments were carried out within the pH
      range of most natural waters, i.e., at neutral (pH 7) or slightly alkaline pH (pH
      9). Tri-sodium citrate and sodium dodecyl sulfate (SDS) were used in the assays
      to prevent interferences due to adsorption processes in the presence of
      multivalent metallic cations and to minimize protein binding. Applying this
      protocol revealed that labile phosphate monoesters always represented the largest
      fraction of enzymatically hydrolyzed P in sewage liquors and sediment porewater.
      Total enzymatically hydrolyzable P (EHP) represented only 16% of the TDP in the
      sediment porewater but up to 43% in sewage liquors. Because most of the enzymes
      used in this study are likely to exist in aquatic ecosystems, the EHP fraction
      might represent a source of potentially bioavailable P of similar magnitude to
      DRP.

PMID- 18044530
TI  - Photolysis of aqueous H2O2: quantum yield and applications for polychromatic UV
      actinometry in photoreactors.
AB  - Methanol is used to measure the yield of *OH radicals produced in the photolysis
      of H2O2 in aqueous solutions. The UV photolysis of H202 generates *OH radicals,
      which in the presence of methanol, oxygen, and phosphate buffer form
      formaldehyde, namely, phi(HCHO) = phi(*OH). The quantum yield of *OH has been
      redetermined in view of literature inconsistencies resulting in phi(*OH) = 1.11
      +/- 0.07 in the excitation range of 205-280 nm. The constancy of phi(*OH) and the
      ease and sensitivity of the formaldehyde product analysis makes the H2O2/CH3OH
      system suitable for polychromatic UV actinometry. In addition, the relatively low
      cost of the main components and the possibility of destroying the methanol before
      disposal qualify the system for both monochromatic and polychromatic actinometry
      in a large volume of water. The H2O2/CH3OH system was applied in different
      commercial UV photoreactors.

PMID- 18044531
TI  - Characteristics of CuO-MoO3-P2O5 catalyst and its catalytic wet oxidation (CWO)
      of dye wastewater under extremely mild conditions.
AB  - In order to develop a catalyst with high activity for catalytic wet oxidation
      (CWO) processing at lower temperatures (35 degrees C) and atmospheric pressure, a
      new CuO-MoO3-P2O5 catalystwas synthesized by a solid-state reaction method and
      was characterized by X-ray diffraction (XRD), Fourier transformation infrared
      spectrometer (FTIR), X-ray photoelectron spectroscopy (XPS), selected area
      electronic diffraction (SAED), scanning electron microscopy (SEM) and energy
      dispersive X-ray spectroscopy (EDXS) for elemental mapping. Methylene blue (MB)
      was adopted to investigate the catalytic activity of CuO-MoO3-P2O5 in CWO
      processing. The results show that this new catalyst has a high catalytic activity
      to decolorize MB under mild condition. The color removal of MB (the initial
      concentration was 0.3 g L(-1) and initial pH was 5) can reach to 99.26% within 10
      min at 35 degrees C and atmospheric pressure. Catalyst lifespan and selectivity
      were also tested, and the results show that after the catalyst was used three
      times, catalyst activity still remains. Selectivity testing shows that CuO-MoO3
      P2O5 has high catalytic activity on degradation of MB, whereas this catalyst has
      less impact on methyl orange (the color removal was 99.65% for MB and 55% for
      methyl orange under the same conditions). According to the experimental results,
      a possible mechanism of catalytic degradation of MB was proposed.

PMID- 18044532
TI  - Reaction of water-stable C60 aggregates with ozone.
AB  - While the reactivity of C60 has been described in a variety of organic solvents,
      little information is available regarding aqueous-based reactions due to
      solubility limitations. In this study, a reaction between C60, as a nanoscale
      suspension, and dissolved ozone in the aqueous phase was investigated. Findings
      indicate a facile reaction occurs, resulting in aggregate dissolution concurrent
      with formation of water-soluble fullerene oxide species. Product analyses,
      including 13C NMR, MS (LDI), FTIR, UV-Vis, and XPS, indicate highly oxidized
      fullerene with an average of approximately 29 oxygen additions per molecule,
      arranged in repeating hydroxyl and hemiketal functionalities. These findings are
      significant in that they (1) demonstrate the feasibility of other aqueous-based
      fullerene chemistries, including those for alternative synthesis routes, which
      might otherwise be considered prohibitive on the basis of solubility limitations,
      and (2) imply that the aqueous reactivity of fullerene-based materials must be
      considered appropriately for accurate assessment of their transport, fate, and
      potential risk(s) in environmental systems.

PMID- 18044534
TI  - Municipal solid waste fueled power generation in China: a case study of waste-to
      energy in Changchun City.
AB  - With rapid economic growth and massive urbanization in China, many cities face
      the problem of municipal solid waste (MSW) disposal. With the lack of space for
      new landfills, waste-to-energy incineration is playing an increasingly important
      role in waste management. Incineration of MSW from Chinese cities presents some
      unique challenges because of its low calorific value (3000-6700 kJ/kg) and high
      water content (approximately 50%). This study reports a novel waste-to-energy
      incineration technology based on co-firing of MSW with coal in a grate
      circulating fluidized bed (CFB) incinerator, which was implemented in the
      Changchun MSW power plant. In 2006, two 260 ton/day incinerators incinerated
      137,325 tons, or approximately one/sixth of the MSW generated in Changchun,
      saving more than 0.2 million m3 landfill space. A total of 46.2 million kWh
      electricity was generated (38,473 tons lignite was also burned as supplementary
      fuel), with an overall fuel-to-electricity efficiency of 14.6%. Emission of air
      pollutants including particulate matters, acidic gases, heavy metals, and dioxins
      was low and met the emission standards for incinerators. As compared to imported
      incineration systems, this new technology has much lower capital and operating
      costs and is expected to play a role in meeting China's demands for MSW disposal
      and alternative energy.

PMID- 18044533
TI  - Electrocatalytic hydrodechlorination of 2,4,5-trichlorobiphenyl on a palladium
      modified nickel foam cathode.
AB  - Palladium-modified materials have been found to be effective electrodes for the
      reductive degradation of chlorinated compounds in aqueous solution. This study
      investigated the electrocatalytic hydrodechlorination (ECH) of polychlorinated
      biphenyls (PCBs) in solvent/surfactant-aided solutions in a palladium-modified
      nickel foam electrode using a divided flow-through cell. The reaction pathways of
      2,4,5-PCB hydrodechlorination were proposed due to the analysis of intermediates
      by GC/MS. The mechanism of electrocatalytic reaction on the Pd/Ni foam cathode
      was examined by studying the effect of surfactant type, sorption behavior of PCBs
      on the electrode, and current densities on the ECH efficiency of PCBs. The
      conversion of PCBs was controlled by the micelle structures of the surfactants
      instead of the charged species. According to the analysis of hydrogen
      transformation processes on the electrode surface, we propose that the ECH
      process was initiated by the transfer of highly active hydrogen atoms [H] from
      the prior polarized Pd particles to the less polarized Pd particles by spillover
      on the Pd/Ni foam cathode. Therefore, the total available surface was larger than
      the originally polarized surface, and [H] could smoothly react with PCBs that
      were adsorbed on the surface. As a result, a high ECH efficiency can be achieved
      with the Pd/Ni foam electrode.

PMID- 18044535
TI  - Reactive adsorption of NO2 at dry conditions on sewage sludge-derived materials.
AB  - Composite inorganic-carbonaceous adsorbents were obtained by pyrolysis of sewage
      sludge at 500, 650, and 950 degrees C for various periods of time. They were used
      as media for reactive adsorption of NO2. The surface structure and chemistry of
      the initial and exhausted materials were analyzed using adsorption of nitrogen,
      XRD, FTIR, and thermal analysis. The results indicate the high level of
      conversion of NO2 to NO with the retention of both species on the surface
      depending on its chemistry. At 650 degrees C as the pyrolysis temperature, the
      most efficient adsorbents were obtained owing to a high reactivity of their
      oxides toward the formation of nitrites and nitrates. When the pyrolysis
      temperature is low, NO2 is reduced to NO on surface sulfides and reacts with
      surface oxides, forming nitrites and nitrates. When adsorbents are obtained at
      950 degrees C, the chemically stable surface prevents the formation of nitrites
      and nitrates, and the majority of NO2 is reduced to NO in the highly carbonized
      carbonaceous phase.

PMID- 18044536
TI  - Catalytic reduction of chlorobenzenes with Pd/Fe nanoparticles: reactive sites,
      catalyst stability, particle aging, and regeneration.
AB  - Monochlorobenzene (MCB), dichlorobenzenes (DCBs), and 1,2,4-trichlorobenzene
      (124TCB) dechlorination experiments in water were carried out with freshly
      synthesized Pd/Fe particles. The pre- and postreacted Pd/Fe samples were
      characterized by applying various analytical techniques (XRD, SEM, TEM, and XPS).
      Chlorinated benzenes could be completely reduced by the Pd/Fe to benzene and the
      reaction followed the pseudo-first-order kinetics. The reaction rates followed
      the order TCB < DCBs < MCB, while among the DCBs the order was 1,4
      dichlorobenzene >1,3-dichlorobenzene > or = 1,2-dichlorobenzene. Insignificant
      reactions were observed with the unpalladized iron, suggesting that Pd was the
      only reactive site in the Pd/Fe particles. The aged Pd/Fe particles exhibited
      significant decrease in its dechlorination reactivity. The loss of Pd/Fe
      reactivity could be due to Pd dislodgment from the aged Pd/Fe particles and Pd
      islets encapsulation by the iron oxides film developed over aging period.
      Reactivity of the aged Pd/Fe could be only partially restored after HCI
      treatment, while regeneration with the NaBH4 reduction method could not restore
      its activity, although zerovalent state of the iron was reinstated.

PMID- 18044537
TI  - Mesoporous nitrogen-doped TiO2 for the photocatalytic destruction of the
      cyanobacterial toxin microcystin-LR under visible light irradiation.
AB  - The presence of the harmful cyanobacterial toxins in water resources worldwide
      drives the development of an innovative and practical water treatment technology
      with great urgency. This study deals with two important aspects: the fabrication
      of mesoporous nitrogen-doped TiO2 (N-TiO2) photocatalysts and their environmental
      application for the destruction of microcystin-LR (MC-LR) under visible light. In
      a nanotechnological sol-gel synthesis method, a nitrogen-containing surfactant
      (dodecylammonium chloride) was introduced as a pore templating material for
      tailor-designing the structural properties of TiO2 and as a nitrogen dopant for
      its visible light response. The resulting N-TiO2 exhibited significantly enhanced
      structural properties including 2-8 nm mesoporous structure (porosity 44%) and
      high surface area of 150 m2/g. Red shift in light absorbance up to 468 nm, 0.9 eV
      lower binding energy of electrons in Ti 2p state, and reduced interplanar
      distance of crystal lattices proved nitrogen doping in the TiO2 lattice. Due to
      its narrow band gap at 2.65 eV, N-TiO2 efficiently degraded MC-LR under visible
      spectrum above 420 nm. Acidic condition (pH 3.5) was more favorable for the
      adsorption and photocatalytic degradation of MC-LR on N-TiO2 due to electrostatic
      attraction forces between negatively charged MC-LR and +6.5 mV charged N-TiO2.
      Even under UV light, MC-LR was decomposed 3-4 times faster using N-TiO2 than
      control TiO2. The degradation pathways and reaction intermediates of MC-LR were
      not directly related to the energy source for TiO2 activation (UV and visible)
      and nature of TiO2 (neat and nitrogen-doped). This study implies a strong
      possibility for the in situ photocatalytic remediation of contaminated water with
      cyanobacterial toxins and other toxic compounds using solar light, a sustainable
      source of energy.

PMID- 18044538
TI  - Characteristics of solidified products containing radioactive molten salt waste.
AB  - The molten salt waste from a pyroprocess to recover uranium and transuranic
      elements is one of the problematic radioactive wastes to be solidified into a
      durable wasteform for its final disposal. By using a novel method, named as the
      GRSS (gel-route stabilization/solidification) method, a molten salt waste was
      treated to produce a unique wasteform. A borosilicate glass as a chemical binder
      dissolves the silicate compounds in the gel products to produce one amorphous
      phase while most of the phosphates are encapsulated by the vitrified phase. Also,
      Cs in the gel product is preferentially situated in the silicate phase, and it is
      vitrified into a glassy phase after a heat treatment. The Sr-containing phase is
      mainly phosphate compounds and encapsulated by the glassy phase. These phenomena
      could be identified by the static and dynamic leaching test that revealed a high
      leach resistance of radionuclides. The leach rates were about 10(-3) - 10(-2)
      g/m2 x day for Cs and 10(-4) - 10(-3) g/m2 x day for Sr, and the leached
      fractions of them were predicted to be 0.89% and 0.39% at 900 days, respectively.
      This paper describes the characteristics of a unique wasteform containing a
      molten salt waste and provides important information on a newly developed
      immobilization technology for salt wastes, the GRSS method.

PMID- 18044539
TI  - What gets recycled: an information theory based model for product recycling.
AB  - This work focuses on developing a concise representation of the material
      recycling potential for products at end-of life. To do this we propose a model
      similar to the "Sherwood Plot", but for products rather than for dilute mixtures.
      The difference is reflected in the material composition and the processing
      systems used for the two different applications. Cost estimates for product
      recycling systems are developed using Shannon's information theory. The resulting
      model is able to resolve the material recycling potential for a wide range of end
      of-life products with vastly different material compositions and recycling rates
      in the U.S. Preliminary data on historical trends in product design suggest a
      significant shift toward less recyclable products.

PMID- 18044540
TI  - Life cycle impact assessment weights to support environmentally preferable
      purchasing in the United States.
AB  - LCA is a quantitative method for understanding the environmental impacts of a
      product, yet all product purchasing decisions are ultimately subjective. Weights
      are the nexus between the quantitative results of LCA and the values-based,
      subjective choices of decision makers. In May 2007, NIST introduced a new
      optional weight set in Version 4.0 of the BEES software. Three key points about
      this new optional weight set are the basis for discussion in this paper: The new
      weight set was created specifically in the context of BEES. It is intended to
      support a practical method to assist environmentally preferable purchasing in the
      United States based on LCIA results. This is in contrast to the weight sets
      currently in BEES, which are based on generalist perspectives. The new weight set
      was created by a multi-stakeholder panel via the AHP method, and is a synthesis
      of panelists' perspectives on the relative importance of each environmental
      impact category in BEES. The weight set draws on each panelist's personal and
      professional understanding of, and value attributed to, each impact category.
      While the synthesized weight set may not equally satisfy each panelist's view of
      impact importance, it does reflect contemporary values in applying LCAto real
      world decisions, and represents one approach others can learn from in producing
      weight sets. The new weight set offers BEES users an additional option for
      synthesizing and comparing the environmental performance of building products and
      making purchasing decisions. In so doing, it strengthens the decision-making
      process, which is important when making product comparisons in the public domain.
      The Weight Set: Across all panelists and with explicit consideration of all time
      horizons, anthropogenic contributions to global warming, weighted at 29%, was
      judged most important, yet not so important that decisions can be made solely on
      the basis of this impact. A strong tail of other concerns include fossil fuel
      depletion (10%), criteria air pollutants (9%), water intake/use (8%), human
      health cancerous effects (8%), ecological toxicity (7%), eutrophication of water
      bodies (6%), land use (6%), and human health noncancerous effects (5%). Also of
      interest are the identified impact areas of concern assigned the lowest weights:
      smog formation (4%), indoor air quality (3%), acidification (3%), and ozone
      depletion (2%). Their low weights may indicate that there is not as much
      immediate concern or that the remedial actions associated with the impact for the
      most part are underway.

PMID- 18044541
TI  - Energy and material balance of CO2 capture from ambient air.
AB  - Current Carbon Capture and Storage (CCS) technologies focus on large, stationary
      sources that produce approximately 50% of global CO2 emissions. We propose an
      industrial technology that captures CO2 directly from ambient air to target the
      remaining emissions. First, a wet scrubbing technique absorbs CO2 into a sodium
      hydroxide solution. The resultant carbonate is transferred from sodium ions to
      calcium ions via causticization. The captured CO2 is released from the calcium
      carbonate through thermal calcination in a modified kiln. The energy consumption
      is calculated as 350 kJ/mol of CO2 captured. It is dominated by the thermal
      energy demand of the kiln and the mechanical power required for air movement. The
      low concentration of CO2 in air requires a throughput of 3 million cubic meters
      of air per ton of CO2 removed, which could result in significant water losses.
      Electricity consumption in the process results in CO2 emissions and the use of
      coal power would significantly reduce to net amount captured. The thermodynamic
      efficiency of this process is low but comparable to other "end of pipe" capture
      technologies. As another carbon mitigation technology, air capture could allow
      for the continued use of liquid hydrocarbon fuels in the transportation sector.

PMID- 18044542
TI  - Open air biocathode enables effective electricity generation with microbial fuel
      cells.
AB  - The reduction of oxygen at the cathode is one of the major bottlenecks of
      microbial fuel cells (MFCs). While research so far has mainly focused on chemical
      catalysis of this oxygen reduction, here we present a continuously wetted cathode
      with microorganisms that act as biocatalysts for oxygen reduction. We combined
      the anode of an acetate oxidizing tubular microbial fuel cell with an open air
      biocathode for electricity production. The maximum power production was 83 +/- 11
      W m(-3) MFC (0.183 L MFC) for batch-fed systems (20-40% Coulombic yield) and 65
      +/- 5 W m(-3) MFC for a continuous system with an acetate loading rate of 1.5 kg
      COD m(-3) day(-1) (90 +/- 3% Coulombic yield). Electrochemical precipitation of
      manganese oxides on the cathodic graphite felt decreased the start-up period with
      approximately 30% versus a non-treated graphite felt. After the start-up period,
      the cell performance was similar for the pretreated and non-treated cathodic
      electrodes. Several reactor designs were tested, and it was found that
      enlargement of the 0.183 L MFC reactor by a factor 2.9-3.8 reduced the volumetric
      power output by 60-67%. Biocathodes alleviate the need to use noble or non-noble
      catalysts for the reduction of oxygen, which increases substantially the
      viability and sustainability of MFCs.

PMID- 18044543
TI  - Toxicogenomic response to chlorination includes induction of major virulence
      genes in Staphylococcus aureus.
AB  - Despite the widespread use of chlorination for microbial control in aqueous
      environments, cellular response mechanisms of human pathogens, such as
      Staphylococcus aureus, against chlorination remain unknown. In this work, genome
      wide transcriptional analysis was performed to elucidate cellular response of S.
      aureusto hypochlorous acid, an active antimicrobial product of chlorination in
      aqueous solution. Our results suggest that hypochlorous acid repressed
      transcription of genes involved in cell wall synthesis, membrane transport,
      protein synthesis, and primary metabolism, while amino acid synthesis genes were
      induced. Furthermore, hypochlorous acid induced transcription of genes encoding
      major virulence factors of S. aureus, such as exotoxins, hemolysins, leukocidins,
      coagulases, and surface adhesion proteins, which all play essential roles in
      staphylococcal virulence. This work implies that chlorination may stimulate
      production of virulence factors, which provides new insight into host-pathogen
      interactions and effects of chlorine application for microbial control.

PMID- 18044544
TI  - Metabolite profiles of di-n-butyl phthalate in humans and rats.
AB  - Di-n-butyl phthalate (DBP) is widely used in consumer products. In humans and in
      rats, DBP is metabolized to mono-n-butyl phthalate (MBP). MBP may also further
      oxidize to other metabolites of DBP. We studied the metabolic profiles of DBP in
      rats and humans to evaluate the similarities between the two species and between
      different exposure scenarios. In rats administered DBP by oral gavage, we
      identified MBP and three urinary oxidative metabolites of DBP: mono-3-oxo-n-butyl
      phthalate, mono-3-hydroxy-n-butyl phthalate (MHBP), and mono-3-carboxypropyl
      phthalate (MCPP). MBP, MHBP, and MCPP were also present in serum, albeit at lower
      levels than in urine. Statistically significant correlations (p < 0.01) existed
      between the concentrations of MBP and the concentrations of MHBP (Pearson
      correlation coefficient r = 0.82 [urine] and r = 0.96 [serum]) and MCPP (r = 0.77
      [urine] and r = 0.97 [serum]). However, the concentrations of these metabolites
      in urine collected 6 h after dosing and in serum 24 h after dosing were not
      correlated, suggesting continuous metabolism of DBP and/or individual differences
      among rats. Serum DBP metabolite concentrations increased with the dose, whereas
      urinary concentrations did not. We also identified MBP, MHBP, and MCPP in the
      urine of four men exposed to DBP bytaking a prescription medication containing
      DBP, and MBP and MCPP in 94 adults with no documented exposure to DBP. In the
      human samples, we observed statistically significant correlations (p < 0.01)
      among the urinary concentrations of MBP and MCPP, although the correlation was
      stronger for the four exposed men (r = 0.99) than for the adults without a
      documented exposure to DBP (r = 0.70). Our results suggest that regardless of
      species and exposure scenario, MBP, the major DBP metabolite, is an optimal
      biomarker of exposure to DBP. In addition to MBP, MCPP and MHBP may be adequate
      biomarkers of exposure to DBP in occupational settings orin potential high
      exposure scenarios.

PMID- 18044545
TI  - Uptake, elimination, and relative distribution of perchlorate in various tissues
      of channel catfish.
AB  - This study was undertaken to determine the kinetics of uptake and elimination of
      perchlorate in channel catfish, Ictalurus punctatus. Perchlorate--an oxidizer
      used in solid fuel rockets, fireworks, and illuminating munitions--has been shown
      to effect thyroid function, causing hormone disruption and potential
      perturbations of metabolic activities. For the uptake study, catfish were exposed
      to 100 mg/L sodium perchlorate for 12 h to 5 d in the laboratory. Perchlorate in
      tissues was analyzed using ion chromatography. The highest perchlorate
      concentrations were found in the head and fillet, indicating that these tissues
      are the most important tissues to analyze when determining perchlorate uptake
      into large fish. To calculate uptake and elimination rate constants for fillet,
      gills, G-I tract, liver, and head, fish were exposed to 100 ppm sodium
      perchlorate for 5 days, and allowed to depurate in clean water for up to 20 days.
      The animals rapidly eliminated the perchlorate accumulated showing the highest
      elimination in fillet (Ke = 1.67 day(-1)) and lowest elimination in liver (Ke =
      0.79 day(-1)).

PMID- 18044546
TI  - Real-time tissue tracking with B-mode ultrasound using speckle and visual
      servoing.
AB  - We present a method for real-time tracking of moving soft tissue with B-mode
      ultrasound (US). The method makes use of the speckle information contained in the
      US images to estimate the in-plane and out-of-plane motion of a fixed target
      relative to the ultrasound scan plane. The motion information is then used as
      closed-loop feedback to a robot which corrects for the target motion. The concept
      is demonstrated for translation motions in an experimental setup consisting of an
      ultrasound speckle phantom, a robot for simulating tissue motion, and a robot
      that performs motion stabilization from US images. This concept shows promise for
      US-guided procedures that require real-time motion tracking and compensation.

PMID- 18044547
TI  - Intra-operative 3D guidance in prostate brachytherapy using a non-isocentric C
      arm.
AB  - Intra-operative guidance in Transrectal Ultrasound (TRUS) guided prostate
      brachytherapy requires localization of inserted radioactive seeds relative to the
      prostate. Seeds were reconstructed using a typical C-arm, and exported to a
      commercial brachytherapy system for dosimetry analysis. Technical obstacles for
      3D reconstruction on a non-isocentric C-arm included pose-dependent C-arm
      calibration; distortion correction; pose estimation of C-arm images; seed
      reconstruction; and C-arm to TRUS registration. In precision-machined hard
      phantoms with 40-100 seeds, we correctly reconstructed 99.8% seeds with a mean 3D
      accuracy of 0.68 mm. In soft tissue phantoms with 45-87 seeds and clinically
      realistic 15 degrees C-arm motion, we correctly reconstructed 100% seeds with an
      accuracy of 1.3 mm. The reconstructed 3D seed positions were then registered to
      the prostate segmented from TRUS. In a Phase-1 clinical trial, so far on 4
      patients with 66-84 seeds, we achieved intra-operative monitoring of seed
      distribution and dosimetry. We optimized the 100% prescribed iso-dose contour by
      inserting an average of 3.75 additional seeds, making intra-operative dosimetry
      possible on a typical C-arm, at negligible additional cost to the existing
      clinical installation.

PMID- 18044548
TI  - A multi-view Opto-Xray imaging system: development and first application in
      trauma surgery.
AB  - The success of minimally invasive trauma and orthopedic surgery procedures has
      resulted in an increase of the use of fluoroscopic imaging. A system aiming to
      reduce the amount of radiation has been introduced by Navab et al. It uses an
      optical imaging system rigidly attached to the gantry such that the optical and X
      ray imaging geometry is identical. As an extension to their solution, we
      developed a multi-view system which offers 3D navigation during trauma surgery
      and orthopedic procedures. We use an additional video camera in an orthogonal
      arrangement to the first video camera and a minimum of two X-ray images.
      Furthermore, tools such as a surgical drill are extended by optical markers and
      tracked with the same optical cameras. Exploiting that the cross ratio is
      invariant in projective geometry, we can estimate the tip of the instrument in
      the X-ray image without external tracking systems. This paper thus introduces the
      first multi-view Opto- Xray system for computer aided surgery. First tests have
      proven the accuracy of the calibration and the instrument tracking. Phantom and
      cadaver experiments were conducted for pedicle screw placement in spinal surgery.
      Using a postoperative CT, we evaluate the quality of the placement of the pedicle
      screws in 3D.

PMID- 18044549
TI  - Towards 3D ultrasound image based soft tissue tracking: a transrectal ultrasound
      prostate image alignment system.
AB  - The emergence of real-time 3D ultrasound (US) makes it possible to consider image
      based tracking of subcutaneous soft tissue targets for computer guided diagnosis
      and therapy. We propose a 3D transrectal US based tracking system for precise
      prostate biopsy sample localisation. The aim is to improve sample distribution,
      to enable targeting of unsampled regions for repeated biopsies, and to make post
      interventional quality controls possible. Since the patient is not immobilized,
      since the prostate is mobile and due to the fact that probe movements are only
      constrained by the rectum during biopsy acquisition, the tracking system must be
      able to estimate rigid transformations that are beyond the capture range of
      common image similarity measures. We propose a fast and robust multi-resolution
      attribute-vector registration approach that combines global and local
      optimization methods to solve this problem. Global optimization is performed on a
      probe movement model that reduces the dimensionality of the search space and thus
      renders optimization efficient. The method was tested on 237 prostate volumes
      acquired from 14 different patients for 3D to 3D and 3D to orthogonal 2D slices
      registration. The 3D-3D version of the algorithm converged correctly in 96.7% of
      all cases in 6.5s with an accuracy of 1.41mm (r.m.s.) and 3.84mm (max). The 3D to
      slices method yielded a success rate of 88.9% in 2.3s with an accuracy of 1.37mm
      (r.m.s.) and 4.3mm (max).

PMID- 18044550
TI  - A probabilistic framework for tracking deformable soft tissue in minimally
      invasive surgery.
AB  - The use of vision based algorithms in minimally invasive surgery has attracted
      significant attention in recent years due to its potential in providing in situ
      3D tissue deformation recovery for intra-operative surgical guidance and robotic
      navigation. Thus far, a large number of feature descriptors have been proposed in
      computer vision but direct application of these techniques to minimally invasive
      surgery has shown significant problems due to free-form tissue deformation and
      varying visual appearances of surgical scenes. This paper evaluates the current
      state-of-the-art feature descriptors in computer vision and outlines their
      respective performance issues when used for deformation tracking. A novel
      probabilistic framework for selecting the most discriminative descriptors is
      presented and a Bayesian fusion method is used to boost the accuracy and temporal
      persistency of soft-tissue deformation tracking. The performance of the proposed
      method is evaluated with both simulated data with known ground truth, as well as
      in vivo video sequences recorded from robotic assisted MIS procedures.

PMID- 18044551
TI  - Precision targeting of liver lesions with a needle-based soft tissue navigation
      system.
AB  - In this study, we assessed the targeting precision of a previously reported
      needle-based soft tissue navigation system. For this purpose, we implanted 10 2
      ml agar nodules into three pig livers as tumor models, and two of the authors
      used the navigation system to target the center of gravity of each nodule. In
      order to obtain a realistic setting, we mounted the livers onto a respiratory
      liver motion simulator that models the human body. For each targeting procedure,
      we simulated the liver biopsy workflow, consisting of four steps: preparation,
      trajectory planning, registration, and navigation. The lesions were successfully
      hit in all 20 trials. The final distance between the applicator tip and the
      center of gravity of the lesion was determined from control computed tomography
      (CT) scans and was 3.5 +/- 1.1 mm on average. Robust targeting precision of this
      order of magnitude would significantly improve the clinical treatment standard
      for various CT-guided minimally invasive interventions in the liver.

PMID- 18044552
TI  - Dynamic MRI scan plane control for passive tracking of instruments and devices.
AB  - This paper describes a novel image-based method for tracking robotic mechanisms
      and interventional devices during Magnetic Resonance Image (MRI)-guided
      procedures. It takes advantage of the multi-planar imaging capabilities of MRI to
      optimally image a set of localizing fiducials for passive motion tracking in the
      image coordinate frame. The imaging system is servoed to adaptively position the
      scan plane based on automatic detection and localization of fiducial artifacts
      directly from the acquired image stream. This closed-loop control system has been
      implemented using an open-source software framework and currently operates with
      GE MRI scanners. Accuracy and performance were evaluated in experiments, the
      results of which are presented here.

PMID- 18044553
TI  - Design and preliminary accuracy studies of an MRI-guided transrectal prostate
      intervention system.
AB  - This paper reports a novel system for magnetic resonance imaging (MRI) guided
      transrectal prostate interventions, such as needle biopsy, fiducial marker
      placement, and therapy delivery. The system utilizes a hybrid tracking method,
      comprised of passive fiducial tracking for initial registration and subsequent
      incremental motion measurement along the degrees of freedom using fiber-optical
      encoders and mechanical scales. Targeting accuracy of the system is evaluated in
      prostate phantom experiments. Achieved targeting accuracy and procedure times
      were found to compare favorably with existing systems using passive and active
      tracking methods. Moreover, the portable design of the system using only standard
      MRI image sequences and minimal custom scanner interfacing allows the system to
      be easily used on different MRI scanners.

PMID- 18044554
TI  - Thoracoscopic surgical navigation system for cancer localization in collapsed
      lung based on estimation of lung deformation.
AB  - We have developed a thoracoscopic surgical navigation system for lung cancer
      localization. In our system, the thoracic cage and mediastinum are localized
      using rigid registration between the intraoperatively digitized surface points
      and the preoperative CT surface model, and then the lung deformation field is
      estimated using nonrigid registration between the registered and digitized point
      datasets on the collapsed lung surface and the preoperative CT lung surface model
      to predict cancer locations. In this paper, improved methods on key components of
      the system are investigated to realize clinically acceptable usability and
      accuracy. Firstly, we implement a non-contact surface digitizer under
      thoracoscopic control using an optically tracked laser pointer. Secondly, we
      establish a rigid registration protocol which minimizes the influence of the
      deformation in different patient's positions by analyzing MR images of
      volunteers. These techniques were evaluated by in vitro and clinical experiments.

PMID- 18044555
TI  - Clinical evaluation of a respiratory gated guidance system for liver punctures.
AB  - We have previously proposed a computer guidance system for liver punctures
      designed for intubated (free breathing) patients. The lack of accuracy reported
      (1 cm) was mostly due to the breathing motion that was not taken into account. In
      this paper we modify our system to synchronise the guidance information on the
      expiratory phases of the patient and present an evaluation on 6 patients of our
      respiratory gated system. Firstly, we show how a specific choice of patient
      allows us to rigorously and passively evaluate the system accuracy. Secondly, we
      demonstrate that our system can provide a guidance information with an error
      below 5 mm during expiratory phases.

PMID- 18044556
TI  - Rapid voxel classification methodology for interactive 3D medical image
      visualization.
AB  - In many medical imaging scenarios, real-time high-quality anatomical data
      visualization and interaction is important to the physician for meaningful
      diagnosis 3D medical data and get timely feedback. Unfortunately, it is still
      difficult to achieve an optimized balance between real-time artifact-free medical
      image volume rendering and interactive data classification. In this paper, we
      present a new segment-based post color-attenuated classification algorithm to
      address this problem. In addition, we apply an efficient numerical integration
      computation technique and take advantage of the symmetric storage format of the
      color lookup table generation matrix. When implemented within our GPU-based
      volume raycasting system, the new classification technique is about 100 times
      faster than the unaccelerated pre-integrated classification approach, while
      achieving the similar or even superior quality volume rendered image. In
      addition, we propose an objective measure of artifacts in rendered medical image
      based on high-frequency spatial image content.

PMID- 18044557
TI  - Towards subject-specific models of the dynamic heart for image-guided mitral
      valve surgery.
AB  - Surgeons need a robust interventional system capable of providing reliable, real
      time information regarding the position and orientation of the surgical targets
      and tools to compensate for the lack of direct vision and to enhance manipulation
      of intracardiac targets during minimally-invasive, off-pump cardiac
      interventions. In this paper, we describe a novel method for creating dynamic,
      pre-operative, subject-specific cardiac models containing the surgical targets
      and surrounding anatomy, and how they are used to augment the intra-operative
      virtual environment for guidance of valvular interventions. The accuracy of these
      pre-operative models was established by comparing the target registration error
      between the mitral valve annulus characterized in the pre-operative images and
      their equivalent structures manually extracted from 3D US data. On average, the
      mitral valve annulus was extracted with a 3.1 mm error across all cardiac phases.
      In addition, we also propose a method for registering the pre-operative models
      into the intra-operative virtual environment.

PMID- 18044558
TI  - Pq-space based non-photorealistic rendering for augmented reality.
AB  - The increasing use of robotic assisted minimally invasive surgery (MIS) provides
      an ideal environment for using Augmented Reality (AR) for performing image guided
      surgery. Seamless synthesis of AR depends on a number of factors relating to the
      way in which virtual objects appear and visually interact with a real
      environment. Traditional overlaid AR approaches generally suffer from a loss of
      depth perception. This paper presents a new AR method for robotic assisted MIS,
      which uses a novel pq-space based non-photorealistic rendering technique for
      providing see-through vision of the embedded virtual object whilst maintaining
      salient anatomical details of the exposed anatomical surface. Experimental
      results with both phantom and in vivo lung lobectomy data demonstrate the visual
      realism achieved for the proposed method and its accuracy in providing high
      fidelity AR depth perception.

PMID- 18044559
TI  - Eye-gaze driven surgical workflow segmentation.
AB  - In today's climate of clinical governance there is growing pressure on surgeons
      to demonstrate their competence, improve standards and reduce surgical errors.
      This paper presents a study on developing a novel eye-gaze driven technique for
      surgical assessment and workflow recovery. The proposed technique investigates
      the use of a Parallel Layer Perceptor (PLP) to automate the recognition of a key
      surgical step in a porcine laparoscopic cholecystectomy model. The classifier is
      eye-gaze contingent but combined with image based visual feature detection for
      improved system performance. Experimental results show that by fusing image
      instrument likelihood measures, an overall classification accuracy of 75% is
      achieved.

PMID- 18044560
TI  - Prior knowledge driven multiscale segmentation of brain MRI.
AB  - We present a novel automatic multiscale algorithm applied to segmentation of
      anatomical structures in brain MRI. The algorithm which is derived from algebraic
      multigrid, uses a graph representation of the image and performs a coarsening
      process that produces a full hierarchy of segments. Our main contribution is the
      incorporation of prior knowledge information into the multiscale framework
      through a Bayesian formulation. The probabilistic information is based on an
      atlas prior and on a likelihood function estimated from a manually labeled
      training set. The significance of our new approach is that the constructed
      pyramid, reflects the prior knowledge formulated. This leads to an accurate and
      efficient methodology for detection of various anatomical structures
      simultaneously. Quantitative validation results on gold standard MRI show the
      benefit of our approach.

PMID- 18044561
TI  - Longitudinal cortical registration for developing neonates.
AB  - Understanding the rapid evolution of cerebral cortical surfaces in developing
      neonates is essential in order to understand normal human brain development and
      to study anatomical abnormalities in preterm infants. Several methods to model
      and align cortical surfaces for cross-sectional studies have been developed.
      However, the registration of cortical surfaces extracted from neonates across
      different gestational ages for longitudinal studies remains difficult because of
      significant cerebral growth. In this paper, we present an automatic cortex
      registration algorithm, based on surface relaxation followed by non-rigid surface
      registration. This technique aims to establish the longitudinal spatial
      correspondence of cerebral cortices for the developing brain in neonates. The
      algorithm has been tested on 5 neonates. Each infant has been scanned at three
      different time points. Quantitative results are obtained by propagating sulci
      across multiple gestational ages and computing the overlap ratios with manually
      established ground-truth.

PMID- 18044562
TI  - Regional homogeneity and anatomical parcellation for fMRI image classification:
      application to schizophrenia and normal controls.
AB  - This paper presents a discriminative model of multivariate pattern
      classification, based on functional magnetic resonance imaging (fMRI) and
      anatomical template. As a measure of brain function, Regional homogeneity (ReHo)
      is calculated voxel by voxel, and then a widely used anatomical template is
      applied on ReHo map to parcelate it into 116 brain regions. The mean and standard
      deviation of ReHo values in each region are extracted as features. Pseudo-Fisher
      Linear Discriminant Analysis (PFLDA) is performed for training samples to
      generate discriminative model. Classification experiments have been carried out
      in 48 schizophrenia patients and 35 normal controls. Under a full leave-one-out
      (LOO) cross-validation, correct prediction rate of 80% is achieved. Anatomical
      parcellation process is proved useful to improve classification rate by a control
      experiment. The discriminative model shows its ability to reveal abnormal brain
      functional activities and identify people with schizophrenia.

PMID- 18044563
TI  - Probabilistic fiber tracking using particle filtering.
AB  - This paper presents a novel and fast probabilistic method for white matter fiber
      tracking from diffusion weighted MRI (DWI). We formulate fiber tracking on a
      nonlinear state space model which is able to capture both smoothness regularity
      of fibers and uncertainties of the local fiber orientations due to noise and
      partial volume effects. The global tracking model is implemented using particle
      filtering, which allows us to recursively compute the posterior distribution of
      the potential fibers. The fiber orientation distribution is theoretically
      formulated for prolate and oblate tensors separately. Fast and efficient sampling
      is realised using the von Mises-Fisher distribution on unit spheres. Given a seed
      point, the method is able to rapidly locate the global optimal fiber and also
      provide a connectivity map. The proposed method is demonstrated on a brain
      dataset.

PMID- 18044564
TI  - SMT: Split and Merge tractography for DT-MRI.
AB  - Diffusion tensor magnetic resonance imaging (DT-MRI) based fiber tractography
      aims at reconstruction of the fiber network of brain. Most commonly employed
      techniques for fiber tractography are based on the numerical integration of the
      principal diffusion directions. Although these approaches generate intuitive and
      easy to interpret results, they are prone to cumulative errors and mostly discard
      the stochastic nature of DT-MRI data. The proposed Split & Merge Tractography
      (SMT) technique aims at overcoming the drawbacks of fiber tractography by
      incorporating it with Markov Chain Monte Carlo techniques. SMT is based on
      clustering diversely distributed short fiber tracts based on their inter
      connectivity. SMT also provides real-time interaction to adjust a user defined
      confidence level for clustering.

PMID- 18044565
TI  - Tract-based morphometry.
AB  - Multisubject statistical analyses of diffusion tensor images in regions of
      specific white matter tracts have commonly measured only the mean value of a
      scalar invariant such as the fractional anisotropy (FA), ignoring the spatial
      variation of FA along the length of fiber tracts. We propose to instead perform
      tract-based morphometry (TBM), or the statistical analysis of diffusion MRI data
      in an anatomical tract-based coordinate system. We present a method for automatic
      generation of white matter tract arc length parameterizations, based on learning
      a fiber bundle model from tractography from multiple subjects. Our tract-based
      coordinate system enables TBM for the detection of white matter differences in
      groups of subjects. We present example TBM results from a study of
      interhemispheric differences in FA.

PMID- 18044566
TI  - Towards whole brain segmentation by a hybrid model.
AB  - Segmenting cortical and sub-cortical structures from 3D brain images is of
      significant practical importance. However, various anatomical structures have
      similar intensity patterns in MRI, and the automatic segmentation of them is a
      challenging task. In this paper, we present a new brain segmentation algorithm
      using a hybrid model. (1) A multi-class classifier, PBT.M2, is proposed for
      learning/computing multi-class discriminative models. The PBT.M2 handles multi
      class patterns more easily than the original probabilistic boosting tree (PBT),
      and it facilitates the process, eventually, toward whole brain segmentation. (2)
      We use an edge field, by learning, to constraint the region boundaries. We show
      the improvements due to the two new aspects both numerically and visually, and
      also compare the results with those by FreeSurfer. Our algorithm is general and
      easy to use, and the results obtained are encouraging.

PMID- 18044567
TI  - A family of principal component analyses for dealing with outliers.
AB  - Principal Component Analysis (PCA) has been widely used for dimensionality
      reduction in shape and appearance modeling. There have been several attempts of
      making PCA robust against outliers. However, there are cases in which a small
      subset of samples may appear as outliers and still correspond to plausible data.
      The example of shapes corresponding to fractures when building a vertebra shape
      model is addressed in this study. In this case, the modeling of "outliers" is
      important, and it might be desirable not only not to disregard them, but even to
      enhance their importance. A variation on PCA that deals naturally with the
      importance of outliers is presented in this paper. The technique is utilized for
      building a shape model of a vertebra, aiming at segmenting the spine out of
      lateral X-ray images. The results show that the algorithm can implement both an
      outlier-enhancing and a robust PCA. The former improves the segmentation
      performance in fractured vertebrae, while the latter does so in the unfractured
      ones.

PMID- 18044568
TI  - Automatic segmentation of articular cartilage in magnetic resonance images of the
      knee.
AB  - To perform cartilage quantitative analysis requires the accurate segmentation of
      each individual cartilage. In this paper we present a model based scheme that can
      automatically and accurately segment each individual cartilage in healthy knees
      from a clinical MR sequence (fat suppressed spoiled gradient recall). This scheme
      consists of three stages; the automatic segmentation of the bones, the extraction
      of the bone-cartilage interfaces (BCI) and segmentation of the cartilages. The
      bone segmentation is performed using three-dimensional active shape models. The
      BCI is extracted using image information and prior knowledge about the likelihood
      of each point belonging to the interface. A cartilage thickness model then
      provides constraints and regularizes the cartilage segmentation performed from
      the BCI. The accuracy and robustness of the approach was experimentally
      validated, with (patellar, tibial and femoral) cartilage segmentations having a
      median DSC of (0.870, 0.855, 0.870), performing significantly better than non
      rigid registration (0.787, 0.814, 0.795). The total cartilage segmentation had an
      average DSC of (0.891), close to the (0.896) obtained using a semi-automatic
      watershed algorithm. The error in quantitative volume and thickness measures was
      (8.29, 4.94, 5.56)% and (0.19, 0.33, 0.10) mm respectively.

PMID- 18044569
TI  - Automated model-based rib cage segmentation and labeling in CT images.
AB  - We present a new model-based approach for an automated labeling and segmentation
      of the rib cage in chest CT scans. A mean rib cage model including a complete
      vertebral column is created out of 29 data sets. We developed a ray search based
      procedure for rib cage detection and initial model pose. After positioning the
      model, it was adapted to 18 unseen CT data. In 16 out of 18 data sets, detection,
      labeling, and segmentation succeeded with a mean segmentation error of less than
      1.3 mm between true and detected object surface. In one case the rib cage
      detection failed, in another case the automated labeling.

PMID- 18044570
TI  - Efficient selection of the most similar image in a database for critical
      structures segmentation.
AB  - Radiotherapy planning needs accurate delineations of the critical structures.
      Atlas-based segmentation has been shown to be very efficient to delineate brain
      structures. However, the construction of an atlas from a dataset of images,
      particularly for the head and neck region, is very difficult due to the high
      variability of the images and can generate over-segmented structures in the
      atlas. To overcome this drawback, we present in this paper an alternative method
      to select as a template the image in a database that is the most similar to the
      patient to be segmented. This similarity is based on a distance between
      transformations. A major contribution is that we do not compute every patient-to
      sample registration to find the most similar template, but only the registration
      of the patient towards an average image. This method has therefore the advantage
      of being computationally very efficient. We present a qualitative and
      quantitative comparison between the proposed method and a classical atlas-based
      segmentation method. This evaluation is performed on a subset of 45 patients
      using a Leave-One-Out method and shows a great improvement of the specificity of
      the results.

PMID- 18044571
TI  - Unbiased white matter atlas construction using diffusion tensor images.
AB  - This paper describes an algorithm for unbiased construction of white matter (WM)
      atlases using full information available to diffusion tensor (DT) images. The key
      component of the proposed algorithm is a novel DT image registration method that
      leverages metrics comparing tensors as a whole and optimizes tensor orientation
      explicitly. The problem of unbiased atlas construction is formulated using the
      approach proposed by Joshi et al., i.e., the unbiased WM atlas is determined by
      finding the mappings that best match the atlas to the images in the population
      and have the least amount of deformation. We show how the proposed registration
      algorithm can be adapted to approximately find the optimal atlas. The utility of
      the proposed approach is demonstrated by constructing a WM atlas of 13 subjects.
      The presented DT registration method is also compared to the approach of matching
      DT images by aligning their fractional anisotropy images using large-deformation
      image registration methods. Our results suggest that using full tensor
      information can better align the orientations of WM fiber bundles.

PMID- 18044572
TI  - Real-time SPECT and 2D ultrasound image registration.
AB  - In this paper we present a technique for fully automatic, real-time 3D SPECT
      (Single Photon Emitting Computed Tomography) and 2D ultrasound image
      registration. We use this technique in the context of kidney lesion diagnosis.
      Our registration algorithm allows a physician to perform an ultrasound exam after
      a SPECT image has been acquired and see in real time the registration of both
      modalities. An automatic segmentation algorithm has been implemented in order to
      display in 3D the positions of the acquired US images with respect to the organs.

PMID- 18044573
TI  - A multiphysics simulation of a healthy and a diseased abdominal aorta.
AB  - Abdominal Aortic Aneurysm is a potentially life-threatening disease if not
      treated adequately. Its pathogenesis is complex and multifactorial and is still
      not fully understood. Many biochemical and biomechanical mechanisms have been
      identified as playing a role in the formation of aneurysms but it is as yet
      unclear what triggers the process. We investigated the role of the relevant
      biomechanical factors, in particular the wall shear stress and the intramural
      wall stress by simulating fluid structure interaction between the blood flow and
      the deforming arterial wall in a healthy abdominal aortic bifurcation, the
      preferred location of the disease. We then extended this study by introducing a
      hypothetical weakening of the aortic wall. Intramural wall stress was
      considerably higher and wall shear stress considerably lower in this
      configuration, supporting the hypothesis that biomechanical aneurysmal growth
      factors are self-sustaining.

PMID- 18044574
TI  - New motion correction models for automatic identification of renal transplant
      rejection.
AB  - Acute rejection is the most common reason of graft failure after kidney
      transplantation and early detection is crucial to survive the transplanted kidney
      function. In this paper, we introduce a new approach for the automatic
      classification of normal and acute rejection transplants from Dynamic Contrast
      Enhanced Magnetic Resonance Imaging (DCE-MRI). The proposed algorithm consists of
      three main steps; the first step isolates the kidney from the surrounding
      anatomical structures. In the second step, new motion correction models are
      employed to account for both the global and local motion of the kidney due to
      patient moving and breathing. Finally, the perfusion curves that show the
      transportation of the contrast agent into the tissue are obtained from the kidney
      and used in the classification of normal and acute rejection transplants.

PMID- 18044575
TI  - Detecting mechanical abnormalities in prostate tissue using FE-based image
      registration.
AB  - An image registration-based elastography algorithm is presented for assessing the
      stiffness of tissue regions inside the prostate for the purpose of detecting
      tumors. A 3D finite-element model of the prostate is built from ultrasound images
      and used to simulate the deformation of the prostate induced by a TRUS probe. To
      reconstruct the stiffness of tissues, their Young's moduli are varied using
      Powell's method so that the mutual information between a simulated and deformed
      image volume is maximized. The algorithm was validated using a gelatin prostate
      phantom embedded with a cylindrical inclusion that simulated a tumor. Results
      from the phantom study showed that the technique could detect the increased
      stiffness of the simulated tumor with a reasonable accuracy.

PMID- 18044576
TI  - Real-time fusion of ultrasound and gamma probe for navigated localization of
      liver metastases.
AB  - Liver metastases are an advanced stage of several types of cancer, usually
      treated with surgery. Intra-operative localization of these lesions is currently
      facilitated by intra-operative ultrasound (IOUS) and palpation, yielding a high
      rate of false positives due to benign abnormal regions. In this paper we present
      the integration of functional nuclear information from a gamma probe with IOUS,
      to provide a synchronized, real-time visualization that facilitates the detection
      of active metastases intra-operatively. We evaluate the system in an ex-vivo
      setup employing a group of physicians and medical technicians and show that the
      addition of functional imaging improves the accuracy of localizing and
      identifying malignant and benign lesions significantly. Furthermore we are able
      to demonstrate that the inclusion of an advanced, augmented visualization
      provides more reliability and confidence on classifying these lesions in the
      presented evaluation setup.

PMID- 18044577
TI  - Fast and robust analysis of dynamic contrast enhanced MRI datasets.
AB  - A fully automated method for quantitative analysis of dynamic contrast-enhanced
      MRI data acquired with low and high field scanners, using spin echo and gradient
      echo sequences, depicting various joints is presented. The method incorporates
      efficient pre-processing techniques and a robust algorithm for quantitative
      assessment of dynamic signal intensity vs. time curves. It provides
      differentiated information to the reader regarding areas with the most active
      perfusion and permits depiction of different disease activity in separate
      compartments of a joint. Additionally, it provides information on the speed of
      contrast agent uptake by various tissues. The method delivers objective and
      easily reproducible results, which have been favourably viewed by a number of
      medical experts.

PMID- 18044578
TI  - Functional near infrared spectroscopy in novice and expert surgeons--a manifold
      embedding approach.
AB  - Monitoring expertise development in surgery is likely to benefit from evaluations
      of cortical brain function. Brain behaviour is dynamic and nonlinear. The aim of
      this paper is to evaluate the application of a nonlinear dimensionality reduction
      technique to enhance visualisation of multidimensional functional Near Infrared
      Spectroscopy (fNIRS) data. Manifold embedding is applied to prefrontal
      haemodynamic signals obtained during a surgical knot tying task from a group of
      62 healthy subjects with varying surgical expertise. The proposed method makes no
      assumption about the functionality of the data set and is shown to be capable of
      recovering the intrinsic low dimensional structure of in vivo brain data. After
      manifold embedding, Earth Mover's Distance (EMD) is used to quantify different
      patterns of cortical behaviour associated with surgical expertise and analyse the
      degree of inter-hemispheric channel pair symmetry.

PMID- 18044579
TI  - A hierarchical unsupervised spectral clustering scheme for detection of prostate
      cancer from magnetic resonance spectroscopy (MRS).
AB  - Magnetic Resonance Spectroscopy (MRS) along with MRI has emerged as a promising
      tool in diagnosis and potentially screening for prostate cancer. Surprisingly
      little work, however, has been done in the area of automated quantitative
      analysis of MRS data for identifying likely cancerous areas in the prostate. In
      this paper we present a novel approach that integrates a manifold learning scheme
      (spectral clustering) with an unsupervised hierarchical clustering algorithm to
      identify spectra corresponding to cancer on prostate MRS. Ground truth location
      for cancer on prostate was determined from the sextant location and maximum size
      of cancer available from the ACRIN database, from where a total of 14 MRS studies
      were obtained. The high dimensional information in the MR spectra is non linearly
      transformed to a low dimensional embedding space and via repeated clustering of
      the voxels in this space, non informative spectra are eliminated and only
      informative spectra retained. Our scheme successfully identified MRS cancer
      voxels with sensitivity of 77.8%, false positive rate of 28.92%, and false
      negative rate of 20.88% on a total of 14 prostate MRS studies. Qualitative
      results seem to suggest that our method has higher specificity compared to a
      popular scheme, z-score, routinely used for analysis of MRS data.

PMID- 18044580
TI  - A clinically motivated 2-fold framework for quantifying and classifying
      immunohistochemically stained specimens.
AB  - Motivated by the current limitations of automated quantitative image analysis in
      discriminating among intracellular immunohistochemical (IHC) staining patterns,
      this paper presents a two-fold approach for IHC characterization that utilizes
      both the protein stain information and the surrounding tissue architecture.
      Through the use of a color unmixing algorithm, stained tissue sections are
      automatically decomposed into the IHC stain, which visualizes the target protein,
      and the counterstain which provides an objective indication of the underlying
      histologic architecture. Feature measures are subsequently extracted from both
      staining planes. In order to characterize the IHC expression pattern, this
      approach exploits the use of a non-traditional feature based on textons. Novel
      biologically motivated filter banks are introduced in order to derive texture
      signatures for different IHC staining patterns. Systematic experiments using this
      approach were used to classify breast cancer tissue microarrays which had been
      previously prepared using immuno-targeted nuclear, cytoplasmic, and membrane
      stains.

PMID- 18044581
TI  - Cell population tracking and lineage construction with spatiotemporal context.
AB  - Automated visual-tracking of cell populations in vitro using phase contrast time
      lapse microscopy is vital for quantitative, systematic and high-throughput
      measurements of cell behaviors. These measurements include the spatiotemporal
      quantification of migration, mitosis, apoptosis, and cell lineage. This paper
      presents an automated cell tracking system that can simultaneously track and
      analyze thousands of cells. The system performs tracking by cycling through frame
      by-frame track compilation and spatiotemporal track linking, combining the power
      of two tracking paradigms. We applied the system to a range of cell populations
      including adult stem cells. The system achieved tracking accuracies in the range
      of 83.8%-92.5%, outperforming previous work by up to 8%.

PMID- 18044582
TI  - Spatiotemporal normalization for longitudinal analysis of gray matter atrophy in
      frontotemporal dementia.
AB  - We present a unified method, based on symmetric diffeomorphisms, for studying
      longitudinal neurodegeneration. Our method first uses symmetric diffeomorphic
      normalization to find a spatiotemporal parameterization of an individual's image
      time series. The second step involves mapping a representative image or set of
      images from the time series into an optimal template space. The template mapping
      is then combined with the intrasubject spatiotemporal map to enable pairwise
      statistical tests to be performed on a population of normalized time series
      images. Here, we apply this longitudinal analysis protocol to study the gray
      matter atrophy patterns induced by frontotemporal dementia (FTD). We sample our
      normalized spatiotemporal maps at baseline (time zero) and time one year to
      generate an annualized atrophy map (AAM) that estimates the annual effect of FTD.
      This spatiotemporal normalization enables us to locate neuroanatomical regions
      that consistently undergo significant annual gray matter atrophy across the
      population. We found the majority of annual atrophy to occur in the frontal and
      temporal lobes in our population of 20 subjects. We also found significant
      effects in the hippocampus, insula and cingulate gyrus. Our novel results,
      significant at p < 0.05 after false discovery rate correction, are represented in
      local template space but also assigned Talairach coordinates and Brodmann and
      Anatomical Automatic Labeling (AAL) labels. This paper shows the statistical
      power of symmetric diffeomorphic normalization for performing deformation-based
      studies of longitudinal atrophy.

PMID- 18044583
TI  - Population based analysis of directional information in serial deformation tensor
      morphometry.
AB  - Deformation morphometry provides a sensitive approach to detecting and mapping
      subtle volume changes in the brain. Population based analyses of this data have
      been used successfully to detect characteristic changes in different
      neurodegenerative conditions. However, most studies have been limited to
      statistical mapping of the scalar volume change at each point in the brain, by
      evaluating the determinant of the Jacobian of the deformation field. In this
      paper we describe an approach to spatial normalisation and analysis of the full
      deformation tensor. The approach employs a spatial relocation and reorientation
      of tensors of each subject. Using the assumption of small changes, we use a
      linear modeling of effects of clinical variables on each deformation tensor
      component across a population. We illustrate the use of this approach by
      examining the pattern of significance and orientation of the volume change
      effects in recovery from alcohol abuse. Results show new local structure which
      was not apparent in the analysis of scalar volume changes.

PMID- 18044584
TI  - Non-parametric diffeomorphic image registration with the demons algorithm.
AB  - We propose a non-parametric diffeomorphic image registration algorithm based on
      Thirion's demons algorithm. The demons algorithm can be seen as an optimization
      procedure on the entire space of displacement fields. The main idea of our
      algorithm is to adapt this procedure to a space of diffeomorphic transformations.
      In contrast to many diffeomorphic registration algorithms, our solution is
      computationally efficient since in practice it only replaces an addition of free
      form deformations by a few compositions. Our experiments show that in addition to
      being diffeomorphic, our algorithm provides results that are similar to the ones
      from the demons algorithm but with transformations that are much smoother and
      closer to the true ones in terms of Jacobians.

PMID- 18044585
TI  - Three-dimensional ultrasound mosaicing.
AB  - The creation of 2D ultrasound mosaics is becoming a common clinical practice with
      a high clinical value. The next step coming along with the increasing
      availability of 2D array transducers is the creation of 3D mosaics. In the
      literature of ultrasound registration, the alignment of multiple images has not
      yet been addressed. Therefore, we propose registration strategies, which are able
      to cope with problems arising by multiple image alignment. Among others, we use
      simultaneous registration which urges the usage of multivariate similarity
      measures. In this paper, we propose alternative multivariate extensions based on
      a maximum likelihood framework. Experimental results show the good performance of
      the proposed registration strategies and similarity measures.

PMID- 18044586
TI  - Automated extraction of lymph nodes from 3-D abdominal CT images using 3-D
      minimum directional difference filter.
AB  - This paper presents a method for extracting lymph node regions from 3-D abdominal
      CT images using 3-D minimum directional difference filter. In the case of surgery
      of colonic cancer, resection of metastasis lesions is performed with resection of
      a primary lesion. Lymph nodes are main route of metastasis and are quite
      important for deciding resection area. Diagnosis of enlarged lymph nodes is quite
      important process for surgical planning. However, manual detection of enlarged
      lymph nodes on CT images is quite burden task. Thus, development of lymph node
      detection process is very helpful for assisting such surgical planning task.
      Although there are several report that present lymph node detection, these
      methods detect lymph nodes primary from PET images or detect in 2-D image
      processing way. There is no method that detects lymph nodes directly from 3-D
      images. The purpose of this paper is to show an automated method for detecting
      lymph nodes from 3-D abdominal CT images. This method employs a 3-D minimum
      directional difference filter for enhancing blob structures with suppressing line
      structures. After that, false positive regions caused by residua and vein are
      eliminated using several kinds of information such as size, blood vessels, air in
      the colon. We applied the proposed method to three cases of 3-D abdominal CT
      images. The experimental results showed that the proposed method could detect
      57.0% of enlarged lymph nodes with 58 FPs per case.

PMID- 18044587
TI  - Non-local means variants for denoising of diffusion-weighted and diffusion tensor
      MRI.
AB  - Diffusion tensor imaging (DT-MRI) is very sensitive to corrupting noise due to
      the non linear relationship between the diffusion-weighted image intensities (DW
      MRI) and the resulting diffusion tensor. Denoising is a crucial step to increase
      the quality of the estimated tensor field. This enhanced quality allows for a
      better quantification and a better image interpretation. The methods proposed in
      this paper are based on the Non-Local (NL) means algorithm. This approach uses
      the natural redundancy of information in images to remove the noise. We introduce
      three variations of the NL-means algorithms adapted to DW-MRI and to DT-MRI.
      Experiments were carried out on a set of 12 diffusion-weighted images (DW-MRI) of
      the same subject. The results show that the intensity based NL-means approaches
      give better results in the context of DT-MRI than other classical denoising
      methods, such as Gaussian Smoothing, Anisotropic Diffusion and Total Variation.

PMID- 18044588
TI  - Quantifying calcification in the lumbar aorta on X-ray images.
AB  - In this paper we propose to use inpainting to estimate the severity of
      atherosclerotic plaques from X-ray projections. Inpainting allows to "remove" the
      plaque and estimate what the background image for an uncalcified aorta would have
      looked like. A measure of plaque severity can then be derived by subtracting the
      inpainting from the original image. In contrast to the current standard of
      categorical calcification scoring from X-rays, our method estimates both the size
      and the density of calcified areas and provides a continuous severity score, thus
      allowing for measurement of more subtle differences. We discuss a class of smooth
      inpainting methods, compare their ability to reconstruct the original images, and
      compare the inpainting based calcification score to the conventional categorical
      score in a longitudinal study on 49 patients addressing correlations of the
      calcification scores with hypertension, a known cardiovascular risk factor.

PMID- 18044589
TI  - Physically motivated enhancement of color images for fiber endoscopy.
AB  - Fiber optics are widely used in flexible endoscopes which are indispensable for
      many applications in diagnosis and therapy. Computer-aided use of fiberscopes
      requires a digital sensor mounted at the proximal end. Most commercially
      available cameras for endoscopy provide the images by means of a regular grid of
      color filters what is known as the Bayer Pattern. Hence, the images suffer from
      false colored spatial moire, which is further stressed by the downgrading fiber
      optic transmission yielding a honey comb pattern. To solve this problem we
      propose a new approach that extends the interpolation between known intensities
      of registered fibers to multi channel color applications. The inventive idea
      takes into account both the Gaussian intensity distribution of each fiber and the
      physical color distribution of the Bayer pattern. Individual color factors for
      interpolation of each fiber area make it possible to simultaneously remove both
      the comb structure from the fiber bundle as well as the Bayer pattern mosaicking
      from the sensor while preserving depicted structures and textures in the scene.

PMID- 18044590
TI  - Signal LMMSE estimation from multiple samples in MRI and DT-MRI.
AB  - A method to estimate the magnitude MR data from several noisy samples is
      presented. It is based on the Linear Minimum Mean Squared Error (LMMSE) estimator
      for the Rician noise model when several scanning repetitions are available. This
      method gives a closed-form analytical solution that takes into account the
      probability distribution of the data as well as the existing level of noise,
      showing a better performance than methods such as the average or the median.

PMID- 18044592
TI  - Improving temporal fidelity in k-t BLAST MRI reconstruction.
AB  - Studies of myocardial motion using magnetic resonance imaging usually require
      multiple breath holds and several methods have been proposed in order to reduce
      the scan time. Rapid imaging using k-t BLAST has gained much attention with its
      high reduction factors and image quality. Temporal smoothing, however, may reduce
      the accuracy when assessing cardiac function. In the present work, a modified
      reconstruction filter is proposed, that preserves more of the high temporal
      frequencies. Artificial decimation of a fully sampled data set was used to
      evaluate the reconstruction filter. Compared to the conventional k-t BLAST
      reconstruction, the modified filter produced images with sharper temporal
      delineation of the myocardial walls. Quantitative analysis by means of regional
      velocity estimation showed that the modified reconstruction filter produced more
      accurate velocity estimations.

PMID- 18044591
TI  - Quantifying heterogeneity in dynamic contrast-enhanced MRI parameter maps.
AB  - Simple summary statistics of Dynamic Contrast-Enhanced MRI (DCE-MRI) parameter
      maps (e.g. the median) neglect the spatial arrangement of parameters, which
      appears to carry important diagnostic and prognostic information. This paper
      describes novel statistics that are sensitive to both parameter values and their
      spatial arrangement. Binary objects are created from 3-D DCE-MRI parameter maps
      by "extruding" each voxel into a fourth dimension; the extrusion distance is
      proportional to the voxel's value. The following statistics are then computed on
      these 4-D binary objects: surface area, volume, surface area to volume ratio, and
      box counting (fractal) dimension. An experiment using 4 low and 5 high grade
      gliomas showed significant differences between the two grades for box counting
      dimension computed for extruded v(e) maps, surface area of extruded K(trans) and
      v(e) maps and the volume of extruded v(e) maps (all p < 0.05). An experiment
      using 18 liver metastases imaged before and after treatment with a vascular
      endothelial growth factor (VEGF) inhibitor showed significant differences for
      surface area to volume ratio computed for extruded K(trans) and v(e) maps (p =
      0.0013 and p = 0.045 respectively).

PMID- 18044593
TI  - Segmentation and classification of breast tumor using dynamic contrast-enhanced
      MR images.
AB  - Accuracy of automatic cancer diagnosis is largely determined by two factors,
      namely, the precision of tumor segmentation, and the suitability of extracted
      features for discrimination between malignancy and benignancy. In this paper, we
      propose a new framework for accurate characterization of tumors in contrast
      enhanced MR images. First, a new graph cut based segmentation algorithm is
      developed for refining coarse manual segmentation, which allows precise
      identification of tumor regions. Second, by considering serial contrast-enhanced
      images as a single spatio-temporal image, a spatio-temporal model of segmented
      tumor is constructed to extract Spatio-Temporal Enhancement Patterns (STEPs).
      STEPs are designed to capture not only dynamic enhancement and architectural
      features, but also spatial variations of pixel-wise temporal enhancement of the
      tumor. While temporal enhancement features are extracted through Fourier
      transform, the resulting STEP framework captures spatial patterns of temporal
      enhancement features via moment invariants and rotation invariant Gabor textures.
      High accuracy of the proposed framework is a direct consequence of this two
      pronged approach, which is validated through experiments yielding, for instance,
      an area of 0.97 under the ROC curve.

PMID- 18044594
TI  - Automatic whole heart segmentation in static magnetic resonance image volumes.
AB  - We present a fully automatic segmentation algorithm for the whole heart (four
      chambers, left ventricular myocardium and trunks of the aorta, the pulmonary
      artery and the pulmonary veins) in cardiac MR image volumes with nearly isotropic
      voxel resolution, based on shape-constrained deformable models. After automatic
      model initialization and reorientation to the cardiac axes, we apply a multi
      stage adaptation scheme with progressively increasing degrees of freedom.
      Particular attention is paid to the calibration of the MR image intensities.
      Detailed evaluation results for the various anatomical heart regions are
      presented on a database of 42 patients. On calibrated images, we obtain an
      average segmentation error of 0.76mm.

PMID- 18044595
TI  - PCA-based magnetic field modeling: application for on-line MR temperature
      monitoring.
AB  - Magnetic Resonance (MR) temperature mapping can be used to monitor temperature
      changes during minimally invasive thermal therapies. However, MR-thermometry
      contains artefacts caused by phase errors induced by organ motion in
      inhomogeneous magnetic fields. This paper proposes a novel correction strategy
      based on a Principal Component Analysis (PCA) to estimate magnetic field
      perturbation assuming a linear magnetic field variation with organ displacement.
      The correction method described in this paper consists of two steps: a magnetic
      field perturbation model is computed in a learning step; subsequently, during the
      intervention, this model is used to reconstruct the magnetic field perturbation
      corresponding to the actual organ position which in turns allow computation of
      motion corrected thermal maps.

PMID- 18044596
TI  - A probabilistic model for haustral curvatures with applications to colon CAD.
AB  - Among the many features used for classification in computer-aided detection (CAD)
      systems targeting colonic polyps, those based on differences between the shapes
      of polyps and folds are most common. We introduce here an explicit parametric
      model for the haustra or colon wall. The proposed model captures the overall
      shape of the haustra and we use it to derive the probability distribution of
      features relevant to polyp detection. The usefulness of the model is demonstrated
      through its application to a colon CAD algorithm.

PMID- 18044597
TI  - LV motion tracking from 3D echocardiography using textural and structural
      information.
AB  - Automated motion reconstruction of the left ventricle (LV) from 3D
      echocardiography provides insight into myocardium architecture and function. Low
      image quality and artifacts make 3D ultrasound image processing a challenging
      problem. We introduce a LV tracking method, which combines textural and
      structural information to overcome the image quality limitations. Our method
      automatically reconstructs the motion of the LV contour (endocardium and
      epicardium) from a sequence of 3D ultrasound images.

PMID- 18044598
TI  - A novel 3D multi-scale lineness filter for vessel detection.
AB  - The branching pattern and geometry of coronary microvessels are of high interest
      to understand and model the blood flow distribution and the processes of contrast
      invasion, ischemic changes and repair in the heart in detail. Analysis is
      performed on high resolution, 3D volumes of the arterial microvasculature of
      entire goat hearts, which are acquired with an imaging cryomicrotome. Multi-scale
      vessel detection is an important step required for a detailed quantitative
      analysis of the coronary microvasculature. Based on visual inspection, the
      derived lineness filter shows promising results on real data and digital
      phantoms, on the way towards accurate computerized reconstructions of entire
      coronary trees. The novel lineness filter exploits the local first and second
      order multi-scale derivatives in order to give an intensity-independent response
      to line centers and to suppress unwanted responses to steep edges.

PMID- 18044599
TI  - Live-vessel: extending livewire for simultaneous extraction of optimal medial and
      boundary paths in vascular images.
AB  - This paper incorporates multiscale vesselness filtering into the Livewire
      framework to simultaneously compute optimal medial axes and boundaries in
      vascular images. To this end, we extend the existing 2D graph search to 3D space
      to optimize not only for spatial variables (x, y), but also for radius values r
      at each node. In addition, we minimize change for both scale and the smallest
      principle curvature and incorporate vessel boundary evidence in our optimization.
      When compared to two sets of DRIVE expert manual tracings, our proposed technique
      reduced the overall segmentation task time by 68.2%, had a similarity ratio of
      0.772 (0.775 between manual), and was 98.2% reproducible.

PMID- 18044600
TI  - A point-wise quantification of asymmetry using deformation fields: application to
      the study of the Crouzon mouse model.
AB  - This paper introduces a novel approach to quantify asymmetry in each point of a
      surface. The measure is based on analysing displacement vectors resulting from
      nonrigid image registration. A symmetric atlas, generated from control subjects
      is registered to a given subject image. A comparison of the resulting
      displacement vectors on the left and right side of the symmetry plane, gives a
      point-wise measure of asymmetry. The asymmetry measure was applied to the study
      of Crouzon syndrome using Micro CT scans of genetically modified mice. Crouzon
      syndrome is characterised by the premature fusion of cranial sutures, which gives
      rise to a highly asymmetric growth. Quantification and localisation of this
      asymmetry is of high value with respect to surgery planning and treatment
      evaluation. Using the proposed method, asymmetry was calculated in each point of
      the surface of Crouzon mice and wild-type mice (controls). Asymmetry appeared in
      similar regions for the two groups but the Crouzon mice were found significantly
      more asymmetric. The localisation ability of the method was in good agreement
      with ratings from a clinical expert. Validating the quantification ability is a
      less trivial task due to the lack of a gold standard. Nevertheless, a comparison
      with a different, but less accurate measure of asymmetry revealed good
      correlation.

PMID- 18044601
TI  - Object localization based on Markov random fields and symmetry interest points.
AB  - We present an approach to detect anatomical structures by configurations of
      interest points, from a single example image. The representation of the
      configuration is based on Markov Random Fields, and the detection is performed in
      a single iteration by the MAX-SUM algorithm. Instead of sequentially matching
      pairs of interest points, the method takes the entire set of points, their local
      descriptors and the spatial configuration into account to find an optimal mapping
      of modeled object to target image. The image information is captured by symmetry
      based interest points and local descriptors derived from Gradient Vector Flow.
      Experimental results are reported for two data-sets showing the applicability to
      complex medical data.

PMID- 18044602
TI  - 2D motion analysis of long axis cardiac tagged MRI.
AB  - The tracking and reconstruction of myocardial motion is critical to the diagnosis
      and treatment of heart disease. Currently, little has been done for the analysis
      of motion in long axis (LA) cardiac images. We propose a new fully automated
      motion reconstruction method for grid- tagged MRI that combines Gabor filters and
      deformable models. First, we use a Gabor filter bank to generate the
      corresponding phase map in the myocardium and estimate the location of grid tag
      intersections. Second, we use a non-rigid registration module driven by thin
      plate splines (TPS) to generate a transformation function between tag
      intersections in two consecutive images. Third, deformable spline models are
      initialized using Fourier domain analysis and tracked during the cardiac cycle
      using the TPS generated transformation function. The splines will then locally
      deform under the influence of gradient flow and image phase information. The
      final motion is decomposed into tangential and normal components corresponding to
      the local orientation of the heart wall. The new method has been tested on LA
      phantoms and in vivo heart data, and its performance has been quantitatively
      validated. The results show that our method can reconstruct the motion field in
      LA cardiac tagged MR images accurately and efficiently.

PMID- 18044603
TI  - MCMC curve sampling for image segmentation.
AB  - We present an algorithm to generate samples from probability distributions on the
      space of curves. We view a traditional curve evolution energy functional as a
      negative log probability distribution and sample from it using a Markov chain
      Monte Carlo (MCMC) algorithm. We define a proposal distribution by generating
      smooth perturbations to the normal of the curve and show how to compute the
      transition probabilities to ensure that the samples come from the posterior
      distribution. We demonstrate some advantages of sampling methods such as
      robustness to local minima, better characterization of multi-modal distributions,
      access to some measures of estimation error, and ability to easily incorporate
      constraints on the curve.

PMID- 18044604
TI  - Automatic centerline extraction of irregular tubular structures using probability
      volumes from multiphoton imaging.
AB  - In this paper, we present a general framework for extracting 3D centerlines from
      volumetric datasets. Unlike the majority of previous approaches, we do not
      require a prior segmentation of the volume nor we do assume any particular
      tubular shape. Centerline extraction is performed using a morphology-guided level
      set model. Our approach consists of: i) learning the structural patterns of a
      tubular-like object, and ii) estimating the centerline of a tubular object as the
      path with minimal cost with respect to outward flux in gray level images. Such
      shortest path is found by solving the Eikonal equation. We compare the
      performance of our method with existing approaches in synthetic, CT, and
      multiphoton 3D images, obtaining substantial improvements, especially in the case
      of irregular tubular objects.

PMID- 18044605
TI  - Gamma-convergence approximation to piecewise smooth medical image segmentation.
AB  - Despite many research efforts, accurate extraction of structures of interest
      still remains a difficult issue in many medical imaging applications. This is
      particularly the case for magnetic resonance (MR) images where image quality
      depends highly on the acquisition protocol. In this paper, we propose a
      variational region based algorithm that is able to deal with spatial
      perturbations of the image intensity directly. Image segmentation is obtained by
      using a gamma-Convergence approximation for a multi-scale piecewise smooth model.
      This model overcomes the limitations of global region models while avoiding the
      high sensitivity of local approaches. The proposed model is implemented
      efficiently using recursive Gaussian convolutions. Numerical experiments on 2
      dimensional human liver MR images show that our model compares favorably to
      existing methods.

PMID- 18044606
TI  - Is a single energy functional sufficient? Adaptive energy functionals and
      automatic initialization.
AB  - Energy functional minimization is an increasingly popular technique for image
      segmentation. However, it is far too commonly applied with hand-tuned parameters
      and initializations that have only been validated for a few images. Fixing these
      parameters over a set of images assumes the same parameters are ideal for each
      image. We highlight the effects of varying the parameters and initialization on
      segmentation accuracy and propose a framework for attaining improved results
      using image adaptive parameters and initializations. We provide an analytical
      definition of optimal weights for functional terms through an examination of
      segmentation in the context of image manifolds, where nearby images on the
      manifold require similar parameters and similar initializations. Our results
      validate that fixed parameters are insufficient in addressing the variability in
      real clinical data, that similar images require similar parameters, and
      demonstrate how these parameters correlate with the image manifold. We present
      significantly improved segmentations for synthetic images and a set of 470
      clinical examples.

PMID- 18044607
TI  - A duality based algorithm for TV-L1-optical-flow image registration.
AB  - Nonlinear image registration is a challenging task in the field of medical image
      analysis. In many applications discontinuities may be present in the displacement
      field, and intensity variations may occur. In this work we therefore utilize an
      energy functional which is based on Total Variation regularization and a robust
      data term. We propose a novel, fast and stable numerical scheme to find the
      minimizer of this energy. Our approach combines a fixed-point procedure derived
      from duality principles combined with a fast thresholding step. We show
      experimental results on synthetic and clinical CT lung data sets at different
      breathing states as well as registration results on inter-subject brain MRIs.

PMID- 18044608
TI  - Deformable 2D-3D registration of the pelvis with a limited field of view, using
      shape statistics.
AB  - Our paper summarizes experiments for measuring the accuracy of deformable 2D-3D
      registration between sets of simulated x-ray images (DRR's) and a statistical
      shape model of the pelvis bones, which includes x-ray attenuation information
      ("density"). In many surgical scenarios, the images contain a truncated view of
      the pelvis anatomy. Our work specifically addresses this problem by examining
      different selections of truncated views as target images. Our atlas is derived by
      applying principal component analysis to a population of up to 110 instance
      shapes. The experiments measure the registration error with a large and truncated
      FOV. A typical accuracy of about 2 mm is achieved in the 2D-3D registration,
      compared with about 1.4 mm of an "optimal" 3D-3D registration.

PMID- 18044609
TI  - Segmentation-driven 2D-3D registration for abdominal catheter interventions.
AB  - 2D-3D registration of abdominal angiographic data is a difficult problem due to
      hard time constraints during the intervention, different vessel contrast in
      volume and image, and motion blur caused by breathing. We propose a novel method
      for aligning 2D Digitally Subtracted Angiograms (DSA) to Computed Tomography
      Angiography (CTA) volumes, which requires no user interaction
      intrainterventionally. In an iterative process, we link 2D segmentation and 2D-3D
      registration using a probability map, which creates a common feature space where
      outliers in 2D and 3D are discarded consequently. Unlike other approaches, we
      keep user interaction low while high capture range and robustness against vessel
      variability and deformation are maintained. Tests on five patient data sets and a
      comparison to two recently proposed methods show the good performance of our
      method.

PMID- 18044610
TI  - Primal/dual linear programming and statistical atlases for cartilage
      segmentation.
AB  - In this paper we propose a novel approach for automatic segmentation of cartilage
      using a statistical atlas and efficient primal/dual linear programming. To this
      end, a novel statistical atlas construction is considered from registered
      training examples. Segmentation is then solved through registration which aims at
      deforming the atlas such that the conditional posterior of the learned (atlas)
      density is maximized with respect to the image. Such a task is reformulated using
      a discrete set of deformations and segmentation becomes equivalent to finding the
      set of local deformations which optimally match the model to the image. We
      evaluate our method on 56 MRI data sets (28 used for the model and 28 used for
      evaluation) and obtain a fully automatic segmentation of patella cartilage volume
      with an overlap ratio of 0.84 with a sensitivity and specificity of 94.06% and
      99.92%, respectively.

PMID- 18044611
TI  - Similarity metrics for groupwise non-rigid registration.
AB  - The use of groupwise registration techniques for average atlas construction has
      been a growing area of research in recent years. One particularly challenging
      component of groupwise registration is finding scalable and effective groupwise
      similarity metrics; these do not always extend easily from pairwise metrics. This
      paper investigates possible choices of similarity metrics and additionally
      proposes a novel metric based on Normalised Mutual Information. The described
      groupwise metrics are quantitatively evaluated on simulated and 3D MR datasets,
      and their performance compared to equivalent pairwise registration.

PMID- 18044612
TI  - A comprehensive system for intraoperative 3D brain deformation recovery.
AB  - During neurosurgery, brain deformation renders preoperative images unreliable for
      localizing pathologic structures. In order to visualize the current brain
      anatomy, it is necessary to nonrigidly warp these preoperative images to reflect
      the intraoperative brain. This can be accomplished using a biomechanical model
      driven by sparse intraoperative information. In this paper, a linear elastic
      model of the brain is developed which can infer volumetric brain deformation
      given the cortical surface displacement. This model was tested on both a
      realistic brain phantom and in vivo, proving its ability to account for large
      brain deformations. Also, an efficient semiautomatic strategy for preoperative
      cortical feature detection is outlined, since accurate segmentation of cortical
      features can aid intraoperative cortical surface tracking.

PMID- 18044613
TI  - Bayesian tracking of tubular structures and its application to carotid arteries
      in CTA.
AB  - This paper presents a Bayesian framework for tracking of tubular structures such
      as vessels. Compared to conventional tracking schemes, its main advantage is its
      non-deterministic character, which strongly increases the robustness of the
      method. A key element of our approach is a dedicated observation model for
      tubular structures in regions with varying intensities. Furthermore, we show how
      the tracking method can be used to obtain a probabilistic segmentation of the
      tracked tubular structure. The method has been applied to track the internal
      carotid artery from CT angiography data of 14 patients (28 carotids) through the
      skull base. This is a challenging problem, owing to the close proximity of bone,
      overlap in intensity values of lumen voxels and (partial volume) bone voxels, and
      the tortuous path of the vessels. The tracking was successful in 25 cases, and
      the extracted path were found to be close (< 1.0mm) to manually traced paths by
      two observers.

PMID- 18044614
TI  - Automatic fetal measurements in ultrasound using constrained probabilistic
      boosting tree.
AB  - Automatic delineation and robust measurement of fetal anat-omical structures in
      2D ultrasound images is a challenging task due to the complexity of the object
      appearance, noise, shadows, and quantity of information to be processed. Previous
      solutions rely on explicit encoding of prior knowledge and formulate the problem
      as a perceptual grouping task solved through clustering or variational
      approaches. These methods are known to be limited by the validity of the
      underlying assumptions and cannot capture complex structure appearances. We
      propose a novel system for fast automatic obstetric measurements by directly
      exploiting a large database of expert annotated fetal anatomical structures in
      ultrasound images. Our method learns to distinguish between the appearance of the
      object of interest and background by training a discriminative constrained
      probabilistic boosting tree classifier. This system is able to handle previously
      unsolved problems in this domain, such as the effective segmentation of fetal
      abdomens. We show results on fully automatic measurement of head circumference,
      biparietal diameter, abdominal circumference and femur length. Unparalleled
      extensive experiments show that our system is, on average, close to the accuracy
      of experts in terms of segmentation and obstetric measurements. Finally, this
      system runs under half second on a standard dual-core PC computer.

PMID- 18044615
TI  - Quantifying effect-specific mammographic density.
AB  - A methodology is introduced for the automated assessment of structural changes of
      breast tissue in mammograms. It employs a generic machine learning framework and
      provides objective breast density measures quantifying the specific biological
      effects of interest. In several illustrative experiments on data from a clinical
      trial, it is shown that the proposed method can quantify effects caused by
      hormone replacement therapy (HRT) at least as good as standard methods. Most
      interestingly, the separation of subpopulations using our approach is
      considerably better than the best alternative, which is interactive. Moreover,
      the automated method is capable of detecting age effects where standard
      methodologies completely fail.

PMID- 18044616
TI  - Revisiting the evaluation of segmentation results: introducing confidence maps.
AB  - We introduce a novel framework, called Confidence Maps Estimating True
      Segmentations (Comets), to store segmentation references for medical images,
      combine multiple references, and measure the discrepancy between a segmented
      object and a reference. The core feature is the use of efficiently encoded
      confidence maps, which reflect the local variations of blur and the presence of
      nearby objects. Local confidence values are defined from expert user input, and
      used to define a new discrepancy error measure, aimed to be directly interpreted
      quantitatively and qualitatively. We illustrate the use of this framework to
      compare different segmentation methods and tune a method's parameters.

PMID- 18044617
TI  - Error analysis of calibration materials on dual-energy mammography.
AB  - Dual-energy mammography can suppress the contrast between adipose and glandular
      tissues and improve the detectability of microcalcifications (MCs). In clinical
      dual-energy mammography, imaging object is human breast, while in calibration
      measurements, only phantoms of breast-tissue-equivalent material can be used. The
      composition and density differences between calibration materials and human
      breast bring the differences of linear attenuation coefficient which lead to the
      calculation errors in dual-energy imaging. In this paper, the magnitude of MC
      thickness error from calibration materials has been analyzed using a first-order
      propagation of error analysis. This analysis shows that the thickness error from
      calibration materials ranges from dozens to thousands of microns which can not be
      ignored when carrying out dual-energy calculations. The evaluation of several
      popular phantoms shows that it is of great importance to adopt the phantom
      materials approaching human breast most.

PMID- 18044619
TI  - Variational guidewire tracking using phase congruency.
AB  - We present a novel method to track a guidewire in cardiac x-ray video. Using
      variational calculus, we derive differential equations that deform a spline,
      subject to intrinsic and extrinsic forces, so that it matches the image data,
      remains smooth, and preserves an a priori length. We analytically derive these
      equations from first principles, and show how they include tangential terms,
      which we include in our model. To address the poor contrast often observed in x
      ray video, we propose using phase congruency as an image-based feature.
      Experimental results demonstrate the success of the method in tracking guidewires
      in low contrast x-ray video.

PMID- 18044618
TI  - A MR compatible mechatronic system to facilitate magic angle experiments in vivo.
AB  - When imaging tendons and cartilage in a MRI scanner, an increase in signal
      intensity is observed when they are oriented at 55 degrees with respect to Bo
      (the "magic angle"). There is a clear clinical importance for considering this
      effect as part of the diagnosis of orthopaedic and other injury. Experimental
      studies of this phenomenon have been made harder by practical difficulties of
      tissue positioning and orientation in the confined environment of cylindrical
      scanners. An MRI compatible mechatronic system has been developed to position a
      variety of limbs inside the field of view of the scanner, to be used as a
      diagnostic and research tool. It is actuated with a novel pneumatic motor
      comprised of a heavily geared down air turbine, and is controlled in a closed
      loop using standard optical encoders. MR compatibility is demonstrated as well as
      the results of preliminary trials used to image the Achilles tendon of human
      volunteers at different orientations. A 4 to 13 fold increase in signal at the
      tendon is observed at the magic angle.

PMID- 18044620
TI  - Endoscopic navigation for minimally invasive suturing.
AB  - Manipulating small objects such as needles, screws or plates inside the human
      body during minimally invasive surgery can be very difficult for less experienced
      surgeons, due to the loss of 3D depth perception. This paper presents an approach
      for tracking a suturing needle using a standard endoscope. The resulting pose
      information of the needle is then used to generate artificial 3D cues on the 2D
      screen to optimally support surgeons during tissue suturing. Additionally, if an
      external tracking device is provided to report the endoscope's position, the
      suturing needle can be tracked in a hybrid fashion with sub-millimeter accuracy.
      Finally, a visual navigation aid can be incorporated, if a 3D surface is
      intraoperatively reconstructed from video or registered from preoperative
      imaging.

PMID- 18044621
TI  - On fiducial target registration error in the presence of anisotropic noise.
AB  - We study the effect of anisotropic noise on target registration error (TRE) by
      using a tracked and calibrated stylus tip as the fiducial registration
      application. We present a simple, efficient unscented Kalman filter algorithm
      that is suitable for fiducial registration even with a small number of fiducials.
      We also derive an equation that predicts TRE under anisotropic noise. The
      predicted TRE values are shown to closely match the simulated TRE values achieved
      using our UKF-based algorithm.

PMID- 18044622
TI  - Rotational roadmapping: a new image-based navigation technique for the
      interventional room.
AB  - For decades, conventional 2D-roadmaping has been the method of choice for image
      based guidewire navigation during endovascular procedures. Only recently have 3D
      roadmapping techniques become available that are based on the acquisition and
      reconstruction of a 3D image of the vascular tree. In this paper, we present a
      new image-based navigation technique called RoRo (Rotational Roadmapping) that
      eliminates the guess-work inherent to the conventional 2D method, but does not
      require a 3D image. Our preliminary clinical results show that there are
      situations in which RoRo is preferred over the existing two methods, thus
      demonstrating potential for filling a clinical niche and complementing the
      spectrum of available navigation tools.

PMID- 18044623
TI  - Bronchoscope tracking without fiducial markers using ultra-tiny electromagnetic
      tracking system and its evaluation in different environments.
AB  - This paper presents a method for bronchoscope tracking without any fiducial
      markers using an ultra-tiny electromagnetic tracker (UEMT) for a bronchoscopy
      guidance system. The proposed method calculates the transformation matrix, which
      shows the relationship between the coordinates systems of the pre-operative CT
      images and the UEMT, by registering bronchial branches segmented from CT images
      and points measured by the UEMT attached at the tip of a bronchoscope. We
      dynamically compute the transformation matrix for every pre-defined number of
      measurements. We applied the proposed method to a bronchial phantom in several
      experimental environments. The experimental results showed the proposed method
      can track a bronchoscope camera with about 3.3mm of target registration error
      (TRE) for wood table environment and 4.0mm of TRE for examination table
      environment.

PMID- 18044624
TI  - Online estimation of the target registration error for n-ocular optical tracking
      systems.
AB  - For current surgical navigation systems optical tracking is state of the art. The
      accuracy of these tracking systems is currently determined statically for the
      case of full visibility of all tracking targets. We propose a dynamic
      determination of the accuracy based on the visibility and geometry of the
      tracking setup. This real time estimation of accuracy has a multitude of
      applications. For multiple camera systems it allows reducing line of sight
      problems and guaranteeing a certain accuracy. The visualization of these
      accuracies allows surgeons to perform the procedures taking to the tracking
      accuracy into account. It also allows engineers to design tracking setups
      interactively guaranteeing a certain accuracy. Our model is an extension to the
      state of the art models of Fitzpatrick et al. and Hoff et al. We model the error
      in the camera sensor plane. The error is propagated using the internal camera
      parameter, camera poses, tracking target poses, target geometry and marker
      visibility, in order to estimate the final accuracy of the tracked instrument.

PMID- 18044625
TI  - Assessment of perceptual quality for gaze-contingent motion stabilization in
      robotic assisted minimally invasive surgery.
AB  - With the increasing sophistication of surgical robots, the use of motion
      stabilisation for enhancing the performance of micro-surgical tasks is an
      actively pursued research topic. The use of mechanical stabilisation devices has
      certain advantages, in terms of both simplicity and consistency. The technique,
      however, can complicate the existing surgical workflow and interfere with an
      already crowded MIS operated cavity. With the advent of reliable vision-based
      real-time and in situ in vivo techniques on 3D-deformation recovery, current
      effort is being directed towards the use of optical based techniques for
      achieving adaptive motion stabilisation. The purpose of this paper is to assess
      the effect of virtual stabilization on foveal/parafoveal vision during robotic
      assisted MIS. Detailed psychovisual experiments have been performed. Results show
      that stabilisation of the whole visual field is not necessary and it is
      sufficient to perform accurate motion tracking and deformation compensation
      within a relatively small area that is directly under foveal vision. The results
      have also confirmed that under the current motion stabilisation regime, the
      deformation of the periphery does not affect the visual acuity and there is no
      indication of the deformation velocity of the periphery affecting foveal
      sensitivity. These findings are expected to have a direct implication on the
      future design of visual stabilisation methods for robotic assisted MIS.

PMID- 18044626
TI  - Prediction of respiratory motion with wavelet-based multiscale autoregression.
AB  - In robotic radiosurgery, a photon beam source, moved by a robot arm, is used to
      ablate tumors. The accuracy of the treatment can be improved by predicting
      respiratory motion to compensate for system delay. We consider a wavelet-based
      multiscale autoregressive prediction method. The algorithm is extended by
      introducing a new exponential averaging parameter and the use of the Moore
      Penrose pseudo inverse to cope with long-term signal dependencies and system
      matrix irregularity, respectively. In test cases, this new algorithm outperforms
      normalized LMS predictors by as much as 50%. With real patient data, we achieve
      an improvement of around 5 to 10%.

PMID- 18044627
TI  - Multi-criteria trajectory planning for hepatic radiofrequency ablation.
AB  - In this paper, we propose a method based on multiple criteria to assist
      physicians in planning percutaneous RFA on liver. We explain how we extracted
      information from literature and interviews with radiologists, and formalized them
      into geometric constraints. We expose then our method to compute the most
      suitable needle insertion in two steps: computation of authorized insertion zones
      and multi-criteria optimization of the trajectory within this zones. We focus on
      the combination of the criteria to optimize and on the optimization step.

PMID- 18044628
TI  - A Bayesian 3D volume reconstruction for confocal micro-rotation cell imaging.
AB  - Recently, micro-rotation confocal microscopy has enabled the acquisition of a
      sequence of slices for a non-adherent living cells where the slices' positions
      are roughly controlled by a dielectric-field biological cage. The high resolution
      volume reconstruction requires then the integration of precise alignment of slice
      positions. We propose in the Bayesian context, a new method combining both slice
      positioning and 3D volume reconstruction simultaneously, which leads naturally to
      an energy minimization procedure of a variational problem. An automatic
      calibration paradigm via Maximum Likelihood estimation (MLE) principle is used
      for the relative hyper-parameter determination. We provide finally experimental
      comparison results on both conventional z-stack confocal images and 3D volume
      reconstruction from micro-rotation slices of the same non-adherent living cell to
      show its potential biomedical application.

PMID- 18044629
TI  - Bias image correction via stationarity maximization.
AB  - Automated acquisitions in microscopy may come along with strong illumination
      artifacts due to poor physical imaging conditions. Such artifacts obviously have
      direct consequences on the efficiency of an image analysis algorithm and on the
      quantitative measures. In this paper, we propose a method to correct illumination
      artifacts on biological images. This correction is based on orthogonal polynomial
      modeling, combined with stationary maximization criteria. To validate the
      proposed method we show that we improve particle detection algorithm.

PMID- 18044630
TI  - Toward optimal matching for 3D reconstruction of brachytherapy seeds.
AB  - X-ray C-arm fluoroscopy is a natural choice for intra-operative seed localization
      in prostate brachytherapy. Resolving the correspondence of seeds in the
      projection images can be modeled as an assignment problem that is NP-hard. Our
      approach rests on the practical observation that the optimal solution has almost
      zero cost if the pose of the C-arm is known accurately. This allowed us to to
      derive an equivalent problem of reduced dimensionality that, with linear
      programming, can be solved efficiently in polynomial time. Additionally, our
      method demonstrates significantly increased robustness to C-arm pose errors when
      compared to the prior art. Because under actual clinical circumstances it is
      exceedingly difficult to track the C-arm, easing on this constraint has
      additional practical utility.

PMID- 18044631
TI  - Alignment of large image series using cubic B-splines tessellation: application
      to transmission electron microscopy data.
AB  - 3D reconstruction from serial 2D microscopy images depends on non-linear
      alignment of serial sections. For some structures, such as the neuronal circuitry
      of the brain, very large images at very high resolution are necessary to permit
      reconstruction. These very large images prevent the direct use of classical
      registration methods. We propose in this work a method to deal with the non
      linear alignment of arbitrarily large 2D images using the finite support
      properties of cubic B-splines. After initial affine alignment, each large image
      is split into a grid of smaller overlapping sub-images, which are individually
      registered using cubic B-splines transformations. Inside the overlapping regions
      between neighboring sub-images, the coefficients of the knots controlling the B
      splines deformations are blended, to create a virtual large grid of knots for the
      whole image. The sub-images are resampled individually, using the new
      coefficients, and assembled together into a final large aligned image. We
      evaluated the method on a series of large transmission electron microscopy images
      and our results indicate significant improvements compared to both manual and
      affine alignment.

PMID- 18044632
TI  - Quality-based registration and reconstruction of optical tomography volumes.
AB  - Ultramicroscopy, a novel optical tomographic imaging modality related to
      fluorescence microscopy, allows to acquire cross-sectional slices of small
      specially prepared biological samples with astounding quality and resolution.
      However, scattering of the fluorescence light causes the quality to decrease
      proportional to the depth of the currently imaged plane. Scattering and beam
      thickness of the excitation laser light cause additional image degradation. We
      perform a physical simulation of the light scattering in order to define a
      quantitative function of image quality with respect to depth. This allows us to
      establish 3D-volumes of quality information in addition to the image data.
      Volumes are acquired at different orientations of the sample, hence providing
      complementary regions of high quality. We propose an algorithm for rigid 3D-3D
      registration of these volumes incorporating voxel quality information, based on
      maximizing an adapted linear correlation term. The quality ratio of the images is
      then used, along with the registration result, to create improved volumes of the
      imaged object. The methods are applied on acquisitions of a mouse brain and mouse
      embryo to create outstanding three-dimensional reconstructions.

PMID- 18044633
TI  - Simultaneous segmentation, kinetic parameter estimation, and uncertainty
      visualization of dynamic PET images.
AB  - We develop a segmentation technique for dynamic PET incorporating the
      physiological parameters for different regions via kinetic modeling. We
      demonstrate the usefulness of our technique on fifteen [11C]Raclopride simulated
      PET images. We show qualitatively and quantitatively that the physiologically
      based algorithm outperforms two classical segmentation techniques. Further, we
      derive a formula to compute and visualize the uncertainty encountered during the
      segmentation.

PMID- 18044634
TI  - Nonlinear analysis of BOLD signal: biophysical modeling, physiological states,
      and functional activation.
AB  - There is an increasing interest in exploiting the biophysical plausible models to
      investigate the physiological mechanisms that underlie observed BOLD response.
      However, most existing studies do not produce reliable model parameter estimates,
      are not robust due to the linearization of the nonlinear model, and do not
      perform statistics test to detect functional activation. To overcome these
      limitations, we developed a general framework for the analysis of fMRI data based
      on nonlinear physiological models. It performs system dynamics analysis to gain
      meaningful insight, followed by global sensitivity analysis for model reduction
      which leads to better system identifiability. Subsequently, a nonlinear filter is
      used to simultaneously estimate the state and parameter of the dynamic system,
      and statistics test is performed to derive activation maps based on such model.
      Furthermore, we investigate the change of the activation maps of these hidden
      physiological variables with experimental paradigm through time as well.

PMID- 18044635
TI  - Effectiveness of the finite impulse response model in content-based fMRI image
      retrieval.
AB  - The thresholded t-map produced by the General Linear Model (GLM) gives an
      effective summary of activation patterns in functional brain images and is widely
      used for feature selection in fMRI related classification tasks. As part of a
      project to build content-based retrieval systems for fMRI images, we have
      investigated ways to make GLM more adaptive and more robust in dealing with fMRI
      data from widely differing experiments. In this paper we report on exploration of
      the Finite Impulse Response model, combined with multiple linear regression, to
      identify the "locally best Hemodynamic Response Function (HRF) for each voxel"
      and to simultaneously estimate activation levels corresponding to several
      stimulus conditions. The goal is to develop a procedure for processing datasets
      of varying natures. Our experiments show that Finite Impulse Response (FIR)
      models with a smoothing factor produce better retrieval performance than does the
      canonical double gamma HRF in terms of retrieval accuracy.

PMID- 18044637
TI  - Customised cytoarchitectonic probability maps using deformable registration:
      primary auditory cortex.
AB  - A novel method is presented for creating a probability map from histologically
      defined cytoarchitectonic data, customised for the anatomy of individual fMRI
      volunteers. Postmortem structural and cytoarchitectonic information from a
      published dataset is combined with high resolution structural MR images using
      deformable registration of a region of interest. In this paper, we have targeted
      the three sub-areas of the primary auditory cortex (located on Heschl's gyrus);
      however, the method could be applied to any other cytoarchitectonic region. The
      resulting probability maps show a significantly higher overlap than previously
      generated maps using the same cytoarchitectonic data, and more accurately span
      the macroanatomical structure of the auditory cortex. This improvement indicates
      a high potential for spatially accurate fMRI analysis, allowing more reliable
      correlation between anatomical structure and function. We validate the approach
      using fMRI data from nine individuals, taken from a published dataset. We compare
      activation for stimuli evoking a pitch percept to activation for acoustically
      matched noise, and demonstrate that the primary auditory cortex (Te1.0) and the
      lateral region Te1.2 are sensitive to pitch, whereas Te1.1 is not.

PMID- 18044636
TI  - Sources of variability in MEG.
AB  - This paper investigates and characterizes sources of variability in MEG signals
      in multi-site, multi-subject studies. Understanding these sources will help to
      develop efficient strategies for comparing and pooling data across repetitions of
      an experiment, across subjects, and across sites. In this work, we investigated
      somatosensory MEG data collected at three different sites and applied variance
      component analysis and nonparametric KL divergence analysis in order to
      characterize the sources of variability. Our analysis showed that inter-subject
      differences are the biggest factor in the signal variability. We demonstrated
      that the timing of the deflections is very consistent in the early somatosensory
      response, which justifies a direct comparison of deflection peak times acquired
      from different visits, subjects, and systems. Compared with deflection peak
      times, deflection magnitudes have larger variation across sites; modeling of this
      variability is necessary for data pooling.

PMID- 18044638
TI  - Segmentation of Q-Ball images using statistical surface evolution.
AB  - In this article, we develop a new method to segment Q-Ball imaging (QBI) data. We
      first estimate the orientation distribution function (ODF) using a fast and
      robust spherical harmonic (SH) method. Then, we use a region-based statistical
      surface evolution on this image of ODFs to efficiently find coherent white matter
      fiber bundles. We show that our method is appropriate to propagate through
      regions of fiber crossings and we show that our results outperform state-of-the
      art diffusion tensor (DT) imaging segmentation methods, inherently limited by the
      DT model. Results obtained on synthetic data, on a biological phantom, on real
      datasets and on all 13 subjects of a public QBI database show that our method is
      reproducible, automatic and brings a strong added value to diffusion MRI
      segmentation.

PMID- 18044639
TI  - Evaluation of shape-based normalization in the corpus callosum for white matter
      connectivity analysis.
AB  - Recently, concerns have been raised that the correspondences computed by
      volumetric registration within homogeneous structures are primarily driven by
      regularization priors that differ among algorithms. This paper explores the
      correspondence based on geometric models for one of those structures, midsagittal
      section of the corpus callosum (MSCC), and compared the result with registration
      paradigms. We use geometric model called continuous medial representation (cm
      rep) to normalize anatomical structures on the basis of medial geometry, and use
      features derived from diffusion tensor tractography for validation. We show that
      shape-based normalization aligns subregions of the MSCC, defined by connectivity,
      more accurately than normalization based on volumetric registration. Furthermore,
      shape-based normalization helps increase the statistical power of group analysis
      in an experiment where features derived from diffusion tensor tractography are
      compared between two cohorts. These results suggest that cm-rep is an appropriate
      tool for normalizing the MSCC in white matter studies.

PMID- 18044640
TI  - Accuracy assessment of global and local atrophy measurement techniques with
      realistic simulated longitudinal data.
AB  - The main goal of this work was to assess the accuracy of several well-known
      methods which provide global (BSI and SIENA) or local (Jacobian integration)
      estimates of longitudinal atrophy in brain structures using Magnetic Resonance
      images. For that purpose, we have generated realistic simulated images which
      mimic the patterns of change obtained from a cohort of 19 real controls and 27
      probable Alzheimer's disease patients. SIENA and BSI results correlate very well
      with gold standard data (BSI mean absolute error < 0.29%; SIENA < 0.44%).
      Jacobian integration was guided by both fluid and FFD-based registration
      techniques and resulting deformation fields and associated Jacobians were
      compared, region by region, with gold standard ones. The FFD registration
      technique provided more satisfactory results than the fluid one. Mean absolute
      error differences between volume changes given by the FFD-based technique and the
      gold standard were: sulcal CSF < 2.49%; lateral ventricles < 2.25%; brain <
      0.36%; hippocampi < 1.42%.

PMID- 18044641
TI  - Combinatorial optimization for electrode labeling of EEG caps.
AB  - An important issue in electroencephalographiy (EEG) experiments is to measure
      accurately the three dimensional (3D) positions of the electrodes. We propose a
      system where these positions are automatically estimated from several images
      using computer vision techniques. Yet, only a set of undifferentiated points are
      recovered this way and remains the problem of labeling them, i.e. of finding
      which electrode corresponds to each point. This paper proposes a fast and robust
      solution to this latter problem based on combinatorial optimization. We design a
      specific energy that we minimize with a modified version of the Loopy Belief
      Propagation algorithm. Experiments on real data show that, with our method, a
      manual labeling of two or three electrodes only is sufficient to get the complete
      labeling of a 64 electrodes cap in less than 10 seconds.

PMID- 18044642
TI  - Analysis of deformation of the human ear and canal caused by mandibular movement.
AB  - Many hearing aid users experience physical discomfort when wearing their device.
      The main contributor to this problem is believed to be deformation of the ear and
      ear canal caused by movement of the mandible. Physical discomfort results from
      added pressure on soft tissue areas in the ear. Identifying features that can
      predict potential deformation is therefore important for identifying problematic
      cases in advance. A study on the physical deformation of the human ear and canal
      due to movement of the mandible is presented. The study is based on laser
      scannings of 30 pairs of ear impressions from 9 female and 21 male subjects. Two
      impressions have been taken from each subject, one with open mouth, and one with
      the mouth closed. All impressions are registered using non-rigid surface
      registration and a shape model is built. From each pair of impressions a
      deformation field is generated and propagated to the shape model, enabling the
      building of a deformation model in the reference frame of the shape model. A
      relationship between the two models is established, showing that the shape
      variation can explain approximately 50% of the variation in the deformation
      model. An hypothesis test for significance of the deformations for each
      deformation field reveals that all subjects have significant deformation at
      Tragus and in the canal. Furthermore, a relation between the magnitude of the
      deformation and the gender of the subject is demonstrated. The results are
      successfully validated by comparing the outcome to the anatomy by using a single
      set of high resolution histological sectionings of the region of interest.

PMID- 18044643
TI  - Shape registration by simultaneously optimizing representation and
      transformation.
AB  - This paper proposes a novel approach that achieves shape registration by
      optimizing shape representation and transformation simultaneously, which are
      modeled by a constrained Gaussian Mixture Model (GMM) and a regularized thin
      plate spline respectively. The problem is formulated within a Bayesian framework
      and solved by an expectation-maximum (EM) algorithm. Compared with the popular
      methods based on landmarks-sliding, its advantages include: (1) It can naturally
      deal with shapes of complex topologies and 3D dimension; (2) It is more robust
      against data noise; (3) The registration performance is better in terms of the
      generalization error of the resultant statistical shape model. These are
      demonstrated on both synthetic and biomedical shapes.

PMID- 18044644
TI  - Landmark correspondence optimization for coupled surfaces.
AB  - Volumetric layers are often encountered in medical images. Unlike solid
      structures, volumetric layers are characterized by double and nested bounding
      surfaces. It is expected that better statistical models can be built by utilizing
      the surface coupleness rather than simply applying the landmarking method on each
      of them separately. We propose an approach to optimizing the landmark
      correspondence on the coupled surfaces by minimizing the description length that
      incorporates local thickness gradient. The evaluations are performed on a set of
      2-D synthetic close coupled contours and a set of real-world open surfaces, the
      skull vaults. Compared with performing landmarking separately on the coupled
      surfaces, the proposed method constructs models that have better generalization
      ability and specificity.

PMID- 18044645
TI  - Mean template for tensor-based morphometry using deformation tensors.
AB  - Tensor-based morphometry (TBM) studies anatomical differences between brain
      images statistically, to identify regions that differ between groups, over time,
      or correlate with cognitive or clinical measures. Using a nonlinear registration
      algorithm, all images are mapped to a common space, and statistics are most
      commonly performed on the Jacobian determinant (local expansion factor) of the
      deformation fields. In, it was shown that the detection sensitivity of the
      standard TBM approach could be increased by using the full deformation tensors in
      a multivariate statistical analysis. Here we set out to improve the common space
      itself, by choosing the shape that minimizes a natural metric on the deformation
      tensors from that space to the population of control subjects. This method avoids
      statistical bias and should ease nonlinear registration of new subjects data to a
      template that is 'closest' to all subjects' anatomies. As deformation tensors are
      symmetric positive-definite matrices and do not form a vector space, all
      computations are performed in the log-Euclidean framework. The control brain B
      that is already the closest to 'average' is found. A gradient descent algorithm
      is then used to perform the minimization that iteratively deforms this template
      and obtains the mean shape. We apply our method to map the profile of anatomical
      differences in a dataset of 26 HIV/AIDS patients and 14 controls, via a log
      Euclidean Hotelling's T2 test on the deformation tensors. These results are
      compared to the ones found using the 'best' control, B. Statistics on both shapes
      are evaluated using cumulative distribution functions of the p-values in maps of
      inter-group differences.

PMID- 18044646
TI  - Shape-based myocardial contractility analysis using multivariate outlier
      detection.
AB  - This paper presents a new approach to regional myocardial contractility analysis
      based on inter-landmark motion (ILM) vectors and multivariate outlier detection.
      The proposed spatio-temporal representation is used to describe the coupled
      changes occurring at pairs of regions of the left ventricle, thus enabling the
      detection of geometrical and dynamic inconsistencies. Multivariate tolerance
      regions are derived from training samples to describe the variability within the
      normal population using the ILM vectors. For new left ventricular datasets,
      outlier detection enables the localization of extreme ILM observations and the
      corresponding myocardial abnormalities. The framework is validated on a
      relatively large sample of 50 subjects and the results show promise in
      localization and visualization of regional left ventricular dysfunctions.

PMID- 18044647
TI  - Orthopedics surgery trainer with PPU-accelerated blood and tissue simulation.
AB  - This paper presents a novel orthopedics surgery training system with both the
      components for modeling as well as simulating the deformation and visualization
      in an efficient way. By employing techniques such as optimization, segmentation
      and center line extraction, the modeling of deformable model can be completed
      with minimal manual involvement. The novel trainer can simulate rigid body, soft
      tissue and blood with state-of-the-art techniques, so that convincing deformation
      and realistic bleeding can be achieved. More important, newly released Physics
      Processing Unit (PPU) is adopted to tackle the high requirement for physics
      related computations. Experiment shows that the acceleration gain from PPU is
      significant for maintaining interactive frame rate under a complex surgical
      environments of orthopedics surgery.

PMID- 18044648
TI  - Interactive contacts resolution using smooth surface representation.
AB  - Accurately describing interactions between medical devices and anatomical
      structures, or between anatomical structures themselves, is an essential step
      towards the adoption of computer-based medical simulation as an alternative to
      traditional training methods. However, while substantial work has been done in
      the area of real-time soft tissue modeling, little has been done to study the
      problem of contacts occurring during tissue manipulation. In this paper we
      introduce a new method for correctly handling complex contacts between various
      combination of rigid and deformable objects. Our approach verifies Signorini's
      law by combining Lagrange multipliers and the status method to solve unilateral
      constraints. Our method handles both concave and convex surfaces by using a
      displacement subdivision strategy, and the proposed algorithm allows interactive
      computation times even in very constrained situations. We demonstrate the
      efficiency of our approach in the context of interventional radiology, with the
      navigation of catheters and guidewires in tortuous vessels and with the
      deployment of coils to treat aneurysms.

PMID- 18044649
TI  - Using statistical shape analysis for the determination of uterine deformation
      states during hydrometra.
AB  - A fundamental prerequisite of hysteroscopy is the proper distension of the
      uterine cavity with a fluid, also known as hydrometra. For a virtual reality
      based simulation of hysteroscopy, the uterus deformation process due to different
      pressure settings has to be modeled. In previous work we have introduced a hybrid
      method, which relies on precomputed deformation states to derive the hydrometra
      changes during runtime. However, new offline computations were necessary for
      every newly introduced organ mesh. This is not viable if a new surgical scene is
      to be generated for every training session. Therefore, we include the deformation
      states during hydrometra into our previously developed statistical shape model
      for undeformed organ instances. This allows deriving the hydrometra steps
      together with new undeformed uterus meshes. These can then be used during the
      interactive simulation for predicting uterus deformation without time-intensive
      precomputation steps.

PMID- 18044650
TI  - Predictive K-PLSR myocardial contractility modeling with phase contrast MR
      velocity mapping.
AB  - With the increasing versatility of CMR, further understanding of intrinsic
      contractility of the myocardium can be achieved by performing subject-specific
      modeling by integrating structural and functional information available. The
      recent introduction of the virtual tagging framework allows for visualization of
      the localized deformation of the myocardium based on phase contrast myocardial
      velocity mapping. The purpose of this study is to examine the use of a non
      linear, Kernel-Partial Least Squares Regression (K-PLSR) predictive motion
      modeling scheme for the virtual tagging framework. The method allows for the
      derivation of a compact non-linear deformation model such that the entire
      deformation field can be predicted by a limited number of control points. When
      applied to virtual tagging, the technique can be used to predictively guide the
      mesh refinement based on the motion of the coarse grid, thus greatly reducing the
      search space and increasing the convergence speed of the algorithm. The
      effectiveness and numerical accuracy of the proposed technique are assessed with
      both numerically simulated data sets and in vivo phase contrast CMR velocity
      mapping from a group of 7 subjects. The technique presented has a distinct
      advantage over the conventional mesh refinement scheme and brings CMR myocardial
      contractility analysis closer to routine clinical practice.

PMID- 18044651
TI  - A coupled finite element model of tumor growth and vascularization.
AB  - We present a model of solid tumor growth which can account for several stages of
      tumorigenesis, from the early avascular phase to the angiogenesis driven
      proliferation. The model combines several previously identified components in a
      consistent framework, including neoplastic tissue growth, blood and oxygen
      transport, and angiogenic sprouting. First experiments with the framework and
      comparisons with observations made on solid tumors in vivo illustrate the
      plausibility of the approach. Explanations of several experimental observations
      are naturally provided by the model. To the best of our knowledge this is the
      first report of a model coupling tumor growth and angiogenesis.

PMID- 18044652
TI  - Autism diagnostics by 3D texture analysis of cerebral white matter gyrifications.
AB  - The importance of accurate early diagnostics of autism that severely affects
      personal behavior and communication skills cannot be overstated.
      Neuropathological studies have revealed an abnormal anatomy of the cerebral white
      matter (CWM) in autistic brains. We explore a possibility of distinguishing
      between autistic and normal brains by a quantitative shape analysis of CWM
      gyrifications on 3D proton density MRI (PD-MRI) images. Our approach consists of
      (i) segmentation of the CWM on a 3D brain image using a deformable 3D boundary;
      (ii) extraction of gyrifications from the segmented CWM, and (iii) shape analysis
      to quantify thickness of the extracted gyrifications and classify autistic and
      normal subjects. The boundary evolution is controlled by two probabilistic models
      of visual appearance of 3D CWM: the learned prior and the current appearance
      model. Initial experimental results suggest that the proposed 3D texture analysis
      is a promising supplement to the current techniques for diagnosing autism.

PMID- 18044654
TI  - Tissue characterization using fractal dimension of high frequency ultrasound RF
      time series.
AB  - This paper is the first report on the analysis of ultrasound RF echo time series
      acquired using high frequency ultrasound. We show that variations in the
      intensity of one sample of RF echo over time is correlated with tissue
      microstructure. To form the RF time series, a high frequency probe and a tissue
      sample were fixed in position and RF signals backscattered from the tissue were
      continuously recorded. The fractal dimension of RF time series was used as a
      feature for tissue classification. Feature values acquired from different areas
      of one tissue type were statistically similar. For animal tissues with different
      cellular microstructure, we successfully used the fractal dimension of RF time
      series to distinguish segments as small as 20 microns with accuracies as high as
      98%. The results of this study demonstrate that the analysis of RF time series is
      a promising approach for distinguishing tissue types with different cellular
      microstructure.

PMID- 18044653
TI  - 3-D analysis of cortical morphometry in differential diagnosis of Parkinson's
      plus syndromes: mapping frontal lobe cortical atrophy in progressive supranuclear
      palsy patients.
AB  - With the ability to study brain anatomy in vivo using magnetic resonance imaging,
      studies on regional brain atrophy suggest possible improvements for differential
      diagnosis of movement disorders with parkinsonian symptoms. In this study, we
      investigate effects of different parkinsonian syndromes on the cortical gray
      matter thickness and the geometric shape of the cerebral cortex. The study
      consists of a total of 24 patients with a diagnosis of probable progressive
      supranuclear palsy (PSP), multiple systems atrophy (MSA) or idiopathic
      Parkinson's disease (IPD). We examine dense estimates of cortical gray matter
      thickness, sulcal depth, and measures of the curvature in a surface-based
      cortical morphometry analysis framework. Group difference results indicate higher
      cortical atrophy rate in the frontal lobe in PSP patients when compared to either
      MSA or IPD. These findings are indicative of the potential use of routine MRI and
      cortical morphometry in performing differential diagnosis in PSP, MSA and IPD.

PMID- 18044655
TI  - Towards intra-operative 3D nuclear imaging: reconstruction of 3D radioactive
      distributions using tracked gamma probes.
AB  - Nuclear medicine imaging modalities assist commonly in surgical guidance given
      their functional nature. However, when used in the operating room they present
      limitations. Pre-operative tomographic 3D imaging can only serve as a vague
      guidance intra-operatively, due to movement, deformation and changes in anatomy
      since the time of imaging, while standard intra-operative nuclear measurements
      are limited to 1D or (in some cases) 2D images with no depth information. To
      resolve this problem we propose the synchronized acquisition of position,
      orientation and readings of gamma probes intra-operatively to reconstruct a 3D
      activity volume. In contrast to conventional emission tomography, here, in a
      first proof-of-concept, the reconstruction succeeds without requiring symmetry in
      the positions and angles of acquisition, which allows greater flexibility. We
      present our results in phantom experiments for sentinel node lymph node
      localization. The results indicate that 3D intra-operative nuclear images can be
      generated in such a setup up to an accuracy equivalent to conventional SPECT
      systems. This technology has the potential to advance standard procedures towards
      intra-operative 3D nuclear imaging and offers a novel approach for robust and
      precise localization of functional information to facilitate less invasive, image
      guided surgery.

PMID- 18044656
TI  - Instrumentation for epidural anesthesia.
AB  - A low-cost, sterilizable and unobtrusive instrumentation device was developed to
      quantify and study the loss-of-resistance technique in epidural anesthesia. In
      the porcine study, the rapid fall of the applied force, plunger displacement and
      fluid pressure, and the oral indication of the anesthesiologists were shown to be
      consistent with the loss-of-resistance. A model based on fluid leakage was
      developed to estimate the pressure from the force and displacement measurements,
      so that the pressure sensor could be omitted in human studies. In both human (in
      vivo) and porcine (in vitro) subjects, we observed that the ligamentum flavum is
      less amenable to saline injection than the interspinous ligament.

PMID- 18044657
TI  - Small animal radiation research platform: imaging, mechanics, control and
      calibration.
AB  - In cancer research, well characterized small animal models of human cancer, such
      as transgenic mice, have greatly accelerated the pace of development of cancer
      treatments. The goal of the Small Animal Radiation Research Platform (SARRP) is
      to make those same models available for the development and evaluation of novel
      radiation therapies. In combination with advanced imaging methods, small animal
      research allows detailed study of biological processes, disease progression, and
      response to therapy, with the potential to provide a natural bridge to the
      clinical environment. The SARRP will realistically model human radiation
      treatment methods in standard animal models. In this paper, we describe the
      mechanical and control structure of the system. This system requires accurate
      calibration of the x-ray beam for both imaging and radiation treatment, which is
      presented in detail in the paper.

PMID- 18044658
TI  - Proof of concept of a simple computer-assisted technique for correcting bone
      deformities.
AB  - We propose a computer-assisted technique for correcting bone deformities using
      the Ilizarov method. Our technique is an improvement over prior art in that it
      does not require a tracking system, navigation hardware and software, or
      intraoperative registration. Instead, we rely on a postoperative CT scan to
      obtain all of the information necessary to plan the correction and compute a
      correction schedule for the patient. Our laboratory experiments using plastic
      phantoms produced deformity corrections accurate to within 3.0 degrees of
      rotation and 1 mm of lengthening.

PMID- 18044659
TI  - Global registration of multiple point sets: feasibility and applications in multi
      fragment fracture fixation.
AB  - An algorithm to globally register multiple 3D data sets (point sets) within a
      general reference frame is proposed. The algorithm uses the Unscented Kalman
      Filter algorithm to simultaneously compute the registration transformations that
      map the data sets together, and to calculate the variances of the registration
      parameters. The data sets are either randomly generated, or collected from a set
      of fractured bone phantoms using Computed Tomography (CT) images. The algorithm
      robustly converges for isotropic Gaussian noise that could have perturbed the
      point coordinates in the data sets. It is also computationally efficient, and
      enables real-time global registration of multiple data sets, with applications in
      computer-assisted orthopaedic trauma surgery.

PMID- 18044660
TI  - Precise estimation of postoperative cup alignment from single standard X-ray
      radiograph with gonadal shielding.
AB  - This paper addresses the problem of estimating postoperative cup alignment from
      single standard X-ray radiograph with gonadal shielding. The widely used
      procedure of evaluation of cup orientation following total hip arthroplasty using
      single standard anteroposterior radiograph is known inaccurate, largely due to
      the wide variability in individual pelvic position relative to X-ray plate. 2D-3D
      image registration methods have been introduced to estimate the rigid
      transformation between a preoperative CT volume and postoperative radiograph(s)
      for an accurate estimation of the postoperative cup alignment relative to an
      anatomical reference extracted from the CT data. However, these methods require
      either multiple radiographs or a radiograph-specific calibration, both of which
      are not avaiable for most retrospective studies. Furthermore, these methods were
      only evaluated on X-ray radiograph(s) without gonadal shielding. In this paper,
      we propose to use a hybrid 2D-3D registration scheme combining an iterative
      landmark-to-ray registration with a 2D-3D intensity-based registration to
      estimate the rigid transfromation for a precise estimation of cup alignment.
      Quantitative and qualitative results evaluated on clinical and cadaveric datasets
      are given which indicate the validity of our approach.

PMID- 18044661
TI  - Fully automated and adaptive detection of amyloid plaques in stained brain
      sections of Alzheimer transgenic mice.
AB  - Automated detection of amyloid plaques (AP) in post mortem brain sections of
      patients with Alzheimer disease (AD) or in mouse models of the disease is a major
      issue to improve quantitative, standardized and accurate assessment of
      neuropathological lesions as well as of their modulation by treatment. We propose
      a new segmentation method to automatically detect amyloid plaques in Congo Red
      stained sections based on adaptive thresholds and a dedicated amyloid
      plaque/tissue modelling. A set of histological sections focusing on anatomical
      structures was used to validate the method in comparison to expert segmentation.
      Original information concerning global amyloid load have been derived from 6
      mouse brains which opens new perspectives for the extensive analysis of such a
      data in 3-D and the possibility to integrate in vivo-post mortem information for
      diagnosis purposes.

PMID- 18044662
TI  - Non-rigid registration of pre-procedural MR images with intra-procedural
      unenhanced CT images for improved targeting of tumors during liver radiofrequency
      ablations.
AB  - In the United States, unenhanced CT is currently the most common imaging modality
      used to guide percutaneous biopsy and tumor ablation. The majority of liver
      tumors such as hepatocellular carcinomas are visible on contrast-enhanced CT or
      MRI obtained prior to the procedure. Yet, these tumors may not be visible or may
      have poor margin conspicuity on unenhanced CT images acquired during the
      procedure. Non-rigid registration has been used to align images accurately, even
      in the presence of organ motion. However, to date, it has not been used
      clinically for radiofrequency ablation (RFA), since it requires significant
      computational infrastructure and often these methods are not sufficient robust.
      We have already introduced a novel finite element based method (FEM) that is
      demonstrated to achieve good accuracy and robustness for the problem of brain
      shift in neurosurgery. In this current study, we adapt it to fuse pre-procedural
      MRI with intra-procedural CT of liver. We also compare its performance with
      conventional rigid registration and two non-rigid registration methods: b-spline
      and demons on 13 retrospective datasets from patients that underwent RFA at our
      institution. FEM non-rigid registration technique was significantly better than
      rigid (p < 10-5), non-rigid b-spline (p < 10-4) and demons (p < 10-4)
      registration techniques. The results of our study indicate that this novel
      technology may be used to optimize placement of RF applicator during CT-guided
      ablations.

PMID- 18044663
TI  - Antonio Berti, Giovanni Brugnoli and the first studies on aphasia in Italy.

PMID- 18044664
TI  - An investigation of attentional contributions to visual errors in right "neglect
      dyslexia".
AB  - One type of error that is sometimes produced by patients with acquired dyslexia
      is the substitution of an orthographically similar word with letters that overlap
      the target either in early or late letter positions. When such errors affect the
      left sides of words, they are usually produced by patients with focal right
      hemisphere lesions who typically show evidence of left neglect in non-reading
      tasks. This pattern has thus been termed "neglect dyslexia". When the right sides
      of words are affected, however, patients frequently fail to show any signs of
      neglect in tasks other than reading. This study presents results from a patient
      with left hemisphere damage, and a very clear pattern of right "neglect" errors
      in reading, on a series of tasks testing attentional and imagery processes. Given
      the magnitude and consistency of the patient's reading errors, there was little
      evidence that these errors resulted from inattention to the right side of space
      or to the right side of an internally generated visual image. It is argued that
      the positional errors result from an impairment to an abstract ordinal code with
      graded activation of letter positions from first to last, and that this code is
      specific to tasks involving orthographic representations.

PMID- 18044665
TI  - Assessment of working memory performance in self-ordered selection tests.
AB  - Several well-known neuropsychological tests of working memory performance,
      hitherto thought to be unrelated, in fact share a common structure termed here
      the self-ordered selection paradigm. Examples include the subject-ordered
      pointing task, variants of the Corsi blocks test, the multiple-location search
      task, and the letter-recitation task. The defining features of the paradigm are
      outlined. A statistical framework for assessing and testing hypotheses about
      working memory capacity in the self-ordered selection paradigm is described. To
      enable neuropsychologists to conduct a rapid statistical analysis of working
      memory performance, a computer program is presented along with detailed practical
      examples of three useful statistical procedures for both single-case and group
      based analysis. The program may be accessed and executed online over the
      Internet.

PMID- 18044666
TI  - The semantic organisation of mass nouns: evidence from semantic refractory access
      dysphasia.
AB  - The conceptual properties and organisation of mass noun concepts are examined in
      a patient (A.Z.) with a semantic refractory access disorder. A cardinal feature
      of this class of disorder is the build up of interference (refractoriness)
      between semantically similar concepts. In a series of written word identification
      tasks, a gradient of semantic relatedness is demonstrated within the broad domain
      of mass noun concepts but not between different word classes. More detailed
      examinations of semantic similarity effects within subcategories of mass concepts
      reveal a variable degree of fine-grain organisation, which may reflect the
      influence of premorbid personal knowledge and experience. Furthermore, it is
      demonstrated that common mass or count noun status did not lead to an enhancement
      of the refractory effects of semantic similarity.

PMID- 18044667
TI  - Self-awareness and the left hemisphere: the dark side of selectively reviewing
      the literature.

PMID- 18044668
TI  - Awareness, desire, and false beliefs: Freud in the light of modern
      neuropsychology.

PMID- 18044669
TI  - Freud and neuropsychology: comments related to anosognosia.

PMID- 18044670
TI  - False beliefs and motivated abnormal emotional behaviour in right brain-damaged
      patients.

PMID- 18044671
TI  - From neurosciences to philosophy of mind.

PMID- 18044672
TI  - "[H]E is no more a person now but a whole climate of opinion" (Auden, 1940).

PMID- 18044673
TI  - The "hard problem" of anosognosia: delusional confabulation and anosognosia.

PMID- 18044674
TI  - Reconciling psychodynamic and neurological perspectives on denial.

PMID- 18044675
TI  - Motivations and emotions contribute to a-rational unconscious dynamics: evidence
      and conceptual clarification.

PMID- 18044676
TI  - Neuro-psychoanalysis may enliven the mindbrain sciences.

PMID- 18044677
TI  - Freud through the centuries.

PMID- 18044678
TI  - Anosognosia, confabulation, and dreaming: a neuropsychological perspective.

PMID- 18044679
TI  - Wake up or dream on? Six questions for Turnbull and Solms.

PMID- 18044680
TI  - What are neuropsychologists up to?

PMID- 18044681
TI  - Role of tiotropium in the treatment of COPD.
AB  - Tiotropium is a potent, long-acting, selective anticholinergic bronchodilator.
      Treatment with tiotropium produces sustained improvements in lung function,
      particularly FEV1 (peak, trough, average, and area under the curve) compared with
      either placebo or ipratropium in patients with moderate to severe COPD.
      Preliminary evidence suggests that treatment with tiotropium may slow the rate of
      decline in FEV1, but this finding awaits confirmation. Tiotropium reduces lung
      hyperinflation, with associated improvements in exercise capacity. Tiotropium,
      compared with either placebo or ipratropium, improves a variety of patient
      centered outcomes, including subjective dyspnea ratings and HRQL scores.
      Tiotropium reduces the frequency of COPD exacerbations and of hospitalizations
      due to exacerbations, but has not been shown to reduce all-cause mortality.
      Compared with the long-acting bronchodilators, tiotropium provides incrementally
      better bronchodilation, but it is not clearly superior in terms of patient
      centered outcomes. Tiotropium has a good safety profile; however patients with
      severe cardiac disease, bladder outlet obstruction, or narrow angle glaucoma were
      excluded from all studies. Medico economic analyses suggest that treatment with
      tiotropium may also be cost-effective, primarily by reducing costs associated
      with hospitalizations.

PMID- 18044682
TI  - Comparison and optimal use of fixed combinations in the management of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and
      mortality worldwide. Indications for the use of long-acting beta-agonists (LABAs)
      and inhaled corticosteroids (ICS) in patients with COPD are described in the
      various international guidelines, but no special recommendations are made
      concerning the use of combination inhalers containing a LABA as well as an ICS.
      To determine the place of combination inhalers in the treatment of COPD we
      reviewed recent literature concerning this subject. On molecular level ICS/LABA
      combination therapy has anti-inflammatory properties which cannot be attributed
      to ICS alone. All clinical studies indicate that the two available combinations
      (salmeterol/fluticasone and formoterol/budesonide) significantly reduce
      exacerbation rate of moderate/severe exacerbations when compared with placebo.
      Some studies also showed a significant reduction in exacerbation rate compared
      with LABA monotherapy, but not compared with ICS monotherapy. From the patient's
      perspective, ICS/LABA combination inhalers are the first choice when both need to
      be prescribed, possibly improving patient compliance for ICS. Currently little
      evidence is available to predict if flexible treatment with LABA/ICS combination
      inhalers will improve disease control in COPD. Further studies are needed to
      elucidate the clinical benefit of combination inhalers versus the individual
      components in different inhalers, and to investigate the clinical benefit of
      flexible dosing of combination inhalers in patients with COPD.

PMID- 18044683
TI  - Genetic predisposition to accelerated decline of lung function in COPD.
AB  - Environmental exposures and genetic susceptibility can contribute to lung
      function decline in chronic obstructive pulmonary disease (COPD). The
      environmental factors are better known than the genetic factors. One of the
      commonest reasons of accelerated forced expiratory volume in one second (FEV1)
      decline in COPD is the continuation of the smoking habit. In addition, COPD
      patients have frequent acute respiratory infections which can also accelerate the
      decline of FEV1. All of the gene variants that have been reported in association
      with accelerated decline of lung function in COPD represent advancement because
      the findings generate plausible hypotheses about the possible mechanisms by which
      gene products could accelerate or avert FEV1 decline. Unfortunately, the results
      have not been consistently replicated and, animal models required to functionally
      assess the genetic findings, have not yet yielded sufficient data. Genome-wide
      association studies should provide more definitive results in COPD and other
      multigenic conditions. Until these studies are reported, the data to date suggest
      that products encoded by the alpha-1 antitrypsin, some matrix metalloproteinases,
      and a number of antioxidant genes are associated with accelerated FEV1 decline in
      COPD. Data on gene variants associated with acute exacerbations of COPD are now
      emerging.

PMID- 18044684
TI  - PDE4 inhibitors as potential therapeutic agents in the treatment of COPD-focus on
      roflumilast.
AB  - Chronic obstructive pulmonary disease is characterized by a rapid decline in lung
      function due to small airway fibrosis, mucus hypersecretion and emphysema. The
      major causative factor for COPD is cigarette smoking that drives an inflammatory
      process that gives rise to leukocyte recruitment, imbalance in protease levels
      and consequently matrix remodeling resulting in small airway fibrosis and loss of
      alveolar tissue. Current drug treatment improves symptoms but do not alter the
      underlying progression of this disease. The failure of antiinflammatory drugs
      like glucocorticosteroids to have a major impact in this disease has hastened the
      need to develop novel therapeutic strategies. Phosphodiesterase (PDE) 4
      inhibitors are novel anti-inflammatory drugs that have recently been show to
      document clinical efficacy in this disease, although their utility is hampered by
      class related side-effects of nausea, emesis and diarrhea. Whilst it is not yet
      clear whether such drugs will prevent emphysema, this is a distinct possibility
      provided experimental observations from preclinical studies translate to man.
      This review will discuss the current standing of PDE4 inhibitors like roflumilast
      as novel treatments for COPD and the potential for developing nonemetic anti
      inflammatory drugs.

PMID- 18044685
TI  - Pulmonary stem cells and the induction of tissue regeneration in the treatment of
      emphysema.
AB  - A common feature of lung disorders with poor treatment options, including
      emphysema, is a failure to initiate a repair process of the alveolar epithelium.
      Several putative stem cell niches in the lung thought to be involved in lung
      homeostasis have been described. Apparently, under pathophysiological conditions
      these resident progenitor cells are unable to recover damaged alveolar
      epithelium, in particular in emphysema. The potential therapeutic effect of
      retinoic acid receptor agonists on various resident lung progenitor cells is
      reviewed.

PMID- 18044687
TI  - COPD heterogeneity: gender differences in the multidimensional BODE index.
AB  - BACKGROUND: The BODE index was recently validated as a multidimensional tool for
      the evaluation of patients with COPD. The influence of gender on the BODE index
      has not been studied. HYPOTHESIS: The contribution of each component of the
      disease to the BODE index may differ according to gender. METHODS: We evaluated
      age, forced expiratory volume in one second (FEV1), Modified Medical Research
      Council (MMRC) score, 6-min walk distance (6MWD), and body mass index (BMI) in 52
      men and 52 women with COPD and the same BODE index. We compared the studied
      parameters between men and women and then performed a multiple regression
      analysis by gender. RESULTS: We found statistically significant differences
      between men and women in all parameters: FEV1 % (55 +/- 17 vs 63 +/- 18, p <
      0.001), MMRC [1 (0-2) vs 1 (1-2) p = 0.03], BMI [28 (26-30) vs 25 (22-30), p =
      0.05], and 6MWD [546 (451-592) vs 462 (419-520), p = 0.001]. Multiple regression
      analysis revealed that each component of the BODE index had different weight
      (beta standardized coefficient) in men and women respectively: FEV1% (0.74 vs
      0.62), MMRC (0.31 vs 0.48), BMI (-0.09 vs -0.17), and 6MWD (0.13 vs 0.10).
      CONCLUSIONS: The contribution of each component to the BODE index differs by
      gender in subjects with similar BODE scores. Long term longitudinal studies will
      help determine the significance of our findings.

PMID- 18044686
TI  - Chronic airflow limitation in developing countries: burden and priorities.
AB  - Respiratory disease has never received priority in relation to its impact on
      health. Estimated DALYs lost in 2002 were 12% globally (similar for
      industrialized and developing countries). Chronic airflow limitation (due mainly
      to asthma and COPD) alone affects more than 100 million persons in the world and
      the majority of them live in developing countries. International guidelines for
      management of asthma (GINA) and COPD (GOLD) have been adopted and their cost
      effectiveness demonstrated in industrialized countries. As resources are scarce
      in developing countries, adaptation of these guidelines using only essential
      drugs is required. It remains for governments to set priorities. To make these
      choices, a set of criteria have been proposed. It is vital that the results of
      scientific investigations are presented in these terms to facilitate their use by
      decision-makers. To respond to this emerging public health problem in developing
      countries, WHO has developed 2 initiatives: "Practical Approach to Lung Health
      (PAL)" and the Global Alliance Against Chronic Respiratory Diseases (GARD)", and
      the International Union Against Tuberculosis and Lung Diseases (The Union) has
      launched a new initiative to increase affordability of essential asthma drugs for
      patients in developing countries termed the "Asthma Drug Facility" (ADF), which
      could facilitate the care of patients living in these parts of the world.

PMID- 18044689
TI  - Cost-effectiveness and healthcare budget impact in Italy of inhaled
      corticosteroids and bronchodilators for severe and very severe COPD patients.
AB  - Current practice guidelines for the treatment of COPD recommend the use of
      combined inhaled corticosteroids and long-acting bronchodilators in severe and
      very severe patients (GOLD stages III and IV). The aim of this study was to
      evaluate, through a simulation model, the economic consequences of this
      recommendation in Italy. We developed a cost-effectiveness analysis (CEA) on five
      alternative therapeutic strategies (salmeterol/fluticasone, SF; formoterol!
      budesonide, FB; salmeterol alone, S; fluticasone alone, F; control, C). Published
      data on the Italian COPD population and efficacy data from international
      reference trials were fitted in a disease progression model based on a Markov
      chain representing severity stages and death. The yearly total direct costs of
      treating COPD patients in Italy was estimated at approximately Euro 7 billion,
      with a mean cost per patient per year of around Euro 2450. Mean survival of the
      cohort is 11.5 years. The C and F strategies were dominated (ie, are associated
      with worse outcomes and higher costs) by all alternatives. SF and FB were the
      most effective strategies, with a slight clinical superiority of SF, but they
      were also marginally more expensive than S. Incremental cost-effectiveness of SF
      vs S was Euro 679.5 per avoided exacerbation and Euro 3.3 per symptom-free day.
      Compared with current practice, the recommended use of combined inhaled
      corticosteroids and long-acting bronchodilators for severe and very severe COPD
      patients has the potential for improving clinical outcomes without increasing
      healthcare costs.

PMID- 18044688
TI  - Outcomes in COPD patients receiving tiotropium or salmeterol plus treatment with
      inhaled corticosteroids.
AB  - Patients with COPD are frequently prescribed inhaled corticosteroids (ICS);
      however, it is unclear whether the treatment with ICS might modify responses to
      inhaled bronchodilators. Two 6-month, randomized, placebo-controlled, double
      blind, double-dummy, parallel-group studies of tiotropium 18 microg once daily,
      compared with salmeterol, 50 microg bid, had been conducted in patients with
      moderate-to-severe COPD. Efficacy was assessed by spirometry, transition dyspnea
      index (TDI), St. George's Respiratory Questionnaire (SGRQ), and exacerbations.
      Data from both studies were combined to form subgroups with regard to concurrent
      use of ICS. 796 patients receiving ICS were separately analyzed from 390 patients
      not receiving ICS. Mean age was 64 years, and pre-bronchodilator FEV1 was 1.06 L
      (ICS group) and 1.13 L (non-ICS group). Both bronchodilators increased morning
      mean +/- SE pre-dose FEV1 compared with placebo (ICS groups: tiotropium 110 +/-
      20 mL, salmeterol 80 +/- 20 mL; non-ICS groups: tiotropium 150 +/- 30 mL,
      salmeterol 110 +/- 30 mL; p > 0.05 for tiotropium vs salmeterol). Improvements in
      TDI and SGRQ and frequency of exacerbations also tended to be more profound for
      tiotropium. Treatment with tiotropium in patients with moderate-to-severe COPD
      was superior to salmeterol in lung function, irrespective of concurrent use of
      ICS.

PMID- 18044691
TI  - Orbital emphysema in COPD with bronchopleural fistula.
AB  - Orbital emphysema is usually a benign, self-limited condition. Intraorbital
      extension of the entrapped air in the absence of an orbital fracture is extremely
      rare. Although benign, a careful periodic monitoring of intraocular pressure,
      optic nerve examinations, and prompt management are warranted in order to prevent
      tension pneumoobitus secondary to increasing intraorbital pressure by the orbital
      air.

PMID- 18044690
TI  - Tobacco consumption in relation to causes of death in an urban population of
      north India.
AB  - BACKGROUND: Noncommunicable diseases have become a public heath problem in India
      concomitant with economic development, leading to increases in tobacco
      consumption, obesity, and changes in diet and lifestyle. Although observation
      suggests that tobacco consumption is a major risk factor for deaths due to
      circulatory, pulmonary, and malignant diseases, such studies are not available
      from most populations in developing countries. SUBJECTS AND METHODS: For the
      period 1999-2001, we studied the randomly selected records of death of 2222 (1385
      men and 837 women) decedents, aged 25-64 years, out of 3034 death records overall
      from the records at Municipal Corporation, Moradabad. All the families of these
      deceased could be contacted individually to find out the causes of death, by
      scientist/doctor administered, informed consented, verbal autopsy questionnaire,
      completed with the help of the spouse and local treating doctor practicing in the
      appropriate healthcare region. Social classes and tobacco intakes were assessed
      by a questionnaire. RESULTS: The prevalence of tobacco consumption, including
      chewing + smoking, were 45% (n = 623) among men and 15% (n = 125) among women
      decedents. However, smoking was observed in 20% and tobacco chewing in 30% of
      male decedents, while only 6% of female decedents smoked and 10% chewed tobacco.
      Social class had no impact on tobacco consumption in men but did influence one
      subgroup >55 years among women, ie, among those who had the highest tobacco
      consumption. Tobacco intakes were significantly more common among decedents dying
      due to circulatory, malignant, and pulmonary diseases, compared with other causes
      (men 61.1%, 76.6%, pulmonary 77.3% vs 31%, P < 0.001; women 27.5%, 75.9%,
      pulmonary 24.6% vs 0.42%, P < 0.001) of mortality, respectively. Pulmonary causes
      included chronic bronchitis and asthma. Circulatory diseases (29.1%, n = 646)
      including heart attacks (10.0%), stroke (7.8%), valvular heart disease (7.2%, n =
      160), sudden cardiac death and inflammatory cardiac disease, each (2.0%, n = 44)
      were the second most common causes of deaths, after infections (41.1%, n = 915).
      Malignant neoplasm (5.8%, n = 131), injury (14.0%, n = 313), and miscellaneous
      causes of deaths, including diabetes mellitus (2.2%, n = 49) were noted in 9.1%,
      (n = 202) of death records. Cancers of the lung (1.6%), oral cavity (1.5%), liver
      (1.1%), stomach (0.9%), breast (0.31%), uterus, cervix, and ovary (0.27%) were
      relatively common causes for deaths due to malignancy. CONCLUSIONS: This study
      shows that tobacco consumption appears to be a major contributor to deaths due to
      circulatory diseases and malignant diseases in India. Social class status had
      little impact on tobacco consumption in male decedents. Rapid changes in diet and
      lifestyle, increases in tobacco consumption, and possibly aging of the
      population, appear to be strongly associated with mortality due to cardiovascular
      diseases and cancer in this middle-income country.

PMID- 18044692
TI  - Influence of male morphology on male mating status and behavior during interunit
      encounters in western lowland gorillas.
AB  - The western lowland gorilla (Gorilla gorilla gorilla) is one of the most sexually
      dimorphic primate species. Mature males are twice the size of females and have
      grey fur on their backs and a fibrous, adipose crest on their heads. Such traits
      are likely to have evolved by sexual selection, either because they confer
      advantages during male-male fights or because females prefer males with more
      dimorphic traits. We developed photogrammetric methods for distance collection of
      morphological data from silverback males frequenting the Lokoue forest clearing
      in Odzala-Kokoua National Park, Republic of the Congo. Body length, head-crest
      size, musculature development, and extent of the grey color on the back were
      assessed in 87 nonbreeding and breeding mature males. Behavioral data were also
      collected during 312 male-male encounters involving 67 mature males in order to
      estimate their level of aggressiveness. The number of females belonging to a
      mature male positively correlated with the male crest size, body length, and
      musculature. Whereas morphological variables did not significantly affect the
      intensity of male-male encounters, the number of females attending male-male
      encounters strongly affected the number of agonistic displays by the two males.
      We discuss the mechanisms through which males with more exaggerated traits could
      obtain a mating advantage, namely male-male fights or female mate choice.

PMID- 18044693
TI  - Strong postcranial size dimorphism in Australopithecus afarensis: results from
      two new resampling methods for multivariate data sets with missing data.
AB  - There is considerable debate over the level of size dimorphism and inferred
      social behavior of Australopithecus afarensis. Most previous studies have
      analyzed size variation in single variables or multiple variables drawn from
      single elements. These approaches suffer from small sample sizes, underscoring
      the need for new techniques that incorporate measurements from multiple
      unassociated elements, reducing the influence of random sampling on size
      variation in fossil samples. One such technique, the template method, has
      recently been proposed but is limited to samples with a template specimen and is
      sensitive to a number of assumptions. Here we present two new resampling methods
      that do not require a template specimen, allow measurements from multiple
      unassociated elements to be included in a single analysis, and allow for
      significance tests between comparative and fossil multivariate data sets with
      missing data. Using these new methods, multivariate postcranial size dimorphism
      is measured using eight measurements of the femur, tibia, humerus, and radius in
      samples of A. afarensis, modern humans, chimpanzees, gorillas, and orangutans.
      Postcranial dimorphism in A. afarensis is similar to that of gorillas and
      orangutans, and significantly greater than in modern humans and chimpanzees.
      Because studies in living primates have examined the association of behavior with
      dimorphism in body mass and craniodental measurements, not postcrania,
      relationships between postcranial dimorphism and social behavior must be
      established to make robust behavioral inferences for A. afarensis. However, the
      results of this and past studies strongly suggest behavioral and mating
      strategies differed between A. afarensis and modern humans.

PMID- 18044694
TI  - Epiphyseal union at the innominate and lower limb in a modern Portuguese skeletal
      sample, and age estimation in adolescent and young adult male and female
      skeletons.
AB  - This study documents the timing of epiphyseal union at the innominate, femur,
      tibia, and fibula in a sample of modern Portuguese skeletons. The sample was
      taken from the Lisbon documented skeletal collection and it is comprised of 57
      females and 49 males between the ages of 9 and 25. Individuals are mostly
      representative of the middle-to-low socioeconomic segment of the early 20th
      century Lisbon population. A total of 18 anatomical locations were examined for
      epiphyseal union using a three-stage scheme: 1) no union; 2) partial union; and
      3) completed union, all traces of fusion having disappeared. Results show that
      females are ahead of males by 1-2 years and provide similar age ranges for the
      stages of union than previous studies. Some variations between studies can be
      explained by methodological differences between dry bone and radiographic
      observations. However, a review of the literature indicates that socioeconomic
      status of a given population seems to be of decisive importance to the rate of
      ossification and most of the differences in skeletal maturation across studies
      and populations can probably be ascribed to different levels of social and
      economic development of the societies in which the individuals lived. Although
      the effects of socioeconomic status in skeletal maturation are greater during
      childhood than in adolescence, as to make the timing of epiphyseal union a
      reliable estimate of age at death, they are not negligible and age estimates
      should take into account the likely socioeconomic status of the individual, whose
      remains are under examination.

PMID- 18044695
TI  - Glial reactions in Parkinson's disease.
AB  - Dopaminergic neurons of the substantia nigra are particularly vulnerable to
      oxidative and inflammatory attack. Such processes may play a crucial role in the
      etiology of Parkinson disease (PD). Since glia are the main generators of these
      processes, the possibility that PD may be caused by glial dysfunction needs to be
      considered. This review concentrates on glial reactions in PD. Reactive
      astrocytes and reactive microglia are abundant in the substantia nigra (SN) of PD
      cases indicating a robust inflammatory state. Glia normally serve neuroprotective
      roles but, given adverse stimulation, they may contribute to damaging chronic
      inflammation. Microglia, the phagocytes of brain, may be the main contributors
      since they can produce large numbers of superoxide anions and other neurotoxins.
      Their toxicity towards dopaminergic neurons has been demonstrated in tissue
      culture and various animal models of PD. The MPTP and alpha-synuclein models are
      of particular interest. Years after exposure to MPTP, inflammation has been
      observed in the SN. This has established that an acute insult to the SN can
      result in a sustained local inflammation. The alpha-synuclein model indicates
      that an endogenous protein can induce inflammation, and, when overexpressed, can
      lead to autosomal dominant PD. Less is known about the role of astrocytes than
      microglia, but they are known to secrete both inflammatory and anti-inflammatory
      molecules and may play a role in modulating microglial activity. Oligodendrocytes
      do not seem to play a role in promoting inflammation although, like neurons, they
      may be damaged by inflammatory processes. Further research concerning glial
      reactions in PD may lead to disease-modifying therapeutic approaches.

PMID- 18044696
TI  - Anger in Parkinson's disease: a case-control study.
AB  - Cognitive-psychiatric features of Parkinson's disease (PD) are common and they
      may be as disabling as the motor features of the disease. PD has been associated
      with stoic and inflexible personality traits. While many features of personality
      have been studied in PD, a systematic study of anger trait and anger expression
      in PD has not been performed. We used the Spanish adapted version of the state
      trait anger Expression Inventory-2 (STAXI-2), comprised of six scales and an
      anger expression index, to measure anger trait and anger expression. There were
      126 PD patients with depressive symptoms and 126 age- and gender-matched
      controls. PD patients had lower levels of state anger (15.8 +/- 3.1 vs. 17.9 +/-
      5.3, P < 0.001), trait anger (19.2 +/- 5.3 vs. 20.7 +/- 6.0, P < 0.05), anger
      expression-out (9.0 +/- 2.5 vs. 10.5 +/- 3.0, P < 0.001), and anger expression
      index (26.1 +/- 8.8 vs. 29.6 +/- 9.4, P = 0.002); and higher levels in anger
      expression-in (14.0 +/- 3.4 vs. 12.2 +/- 3.2, P < 0.001), anger control-out (18.6
      +/- 5.0 vs. 16.1 +/- 5.0, P < 0.001), and anger control-in (14.3 +/- 4.7 vs. 13.0
      +/- 4.5, P < 0.05) than controls. These differences persisted in analyses
      adjusting for age, gender, and depressive symptoms. CONCLUSIONS: PD patients
      showed lower levels of external expression of anger and higher levels of control
      of anger. Our results demonstrate another dimension to the stoic personality
      trait seen in PD.

PMID- 18044697
TI  - A comparison of the mini mental state exam to the Montreal cognitive assessment
      in identifying cognitive deficits in Parkinson's disease.
AB  - Dementia is an important and increasingly recognized problem in Parkinson's
      disease (PD). The mini-mental state examination (MMSE) often fails to detect
      early cognitive decline. The Montreal cognitive assessment (MoCA) is a brief tool
      developed to detect mild cognitive impairment that assesses a broader range of
      domains frequently affected in PD. The scores on the MMSE and the MoCA were
      compared in 88 patients with PD. A pronounced ceiling effect was observed with
      the MMSE but not with the MoCA. The range and standard deviation of scores was
      larger with the MoCA(7-30, 4.26) than with the MMSE(16-30, 2.55). The percentage
      of subjects scoring below a cutoff of 26/30 (used by others to detect mild
      cognitive impairment) was higher on the MoCA (32%) than on the MMSE (11%) (P <
      0.000002). Compared to the MMSE, the MoCA may be a more sensitive tool to
      identify early cognitive impairment in PD.

PMID- 18044698
TI  - Cortical evoked potentials from pallidal stimulation in patients with primary
      generalized dystonia.
AB  - Deep brain stimulation (DBS) of globus pallidus internus (GPi) has emerged as an
      effective treatment for primary generalized dystonia. However, the physiological
      mechanisms of improvement are not fully understood. Cortical activity in response
      to pallidal stimulation was recorded in 6 patients with primary generalized
      dystonia >6 months after bilateral GPi DBS. Scalp electroencephalogram was
      recorded using 60 surface electrodes during 10 Hz bipolar pallidal DBS at each
      electrode contact pair. Anatomical position of the electrode contacts in relation
      to the GPi, medial medullary lamina and globus pallidus externus (GPe) was
      determined from the postoperative stereotactic MRI. In all six patients an evoked
      potential (EP) was observed with average onset latency of 10.9 ms +/- 0.77, peak
      latency 26.6 ms +/- 1.6, distributed mainly over the ipsilateral hemisphere,
      maximal centrally. The mean amplitude of this potential was larger with
      stimulation in posteroventral GPi than in GPe (3.36 microV vs. 0.50 microV, P <
      0.0001). The EP was absent in one patient-side, ipsilateral to a previous
      thalamotomy. Low frequency GPi stimulation produces an EP distributed centrally
      over the ipsilateral hemisphere. The latency and distribution of the EP are
      consistent with stimulation of pallidothalamic neurons projecting to the
      sensorimotor cortex. Because the EP is larger and more consistently present with
      stimulation of posteroventral GPi than GPe, it may provide a physiological tool
      to identify contacts within the optimal surgical target.

PMID- 18044699
TI  - A Bayesian reconstruction method for micro-rotation imaging in light microscopy.
AB  - The authors present a three-dimensional (3D) reconstruction algorithm and
      reconstruction-based deblurring method for light microscopy using a micro
      rotation device. In contrast to conventional 3D optical imaging where the focal
      plane is shifted along the optical axis, micro-rotation imaging employs
      dielectric fields to rotate the object inside a fixed optical set-up. To address
      this entirely new 3D-imaging modality, the authors present a reconstruction
      algorithm based on Bayesian inversion theory and use the total variation function
      as a structure prior. The spectral properties of the reconstruction by
      simulations that illustrate the strengths and the weaknesses of the micro
      rotation approach, compared with conventional 3D optical imaging, were studied.
      The reconstruction from real data sets shows that this method is promising for 3D
      reconstruction and offers itself as a deblurring method using a reconstruction
      based procedure for removing out-of-focus light from the micro-rotation image
      series.

PMID- 18044700
TI  - The hardness kernel as the basis for global and local reactivity indices.
AB  - In a very recent article (Torrent-Sucarrat et al., J Comput Chem 2007, 28, 574),
      we have shown how to evaluate the global hardness for polyatomic molecules using
      a hardness kernel approximation. We present here an extension of this previous
      work by improving the model used to evaluate the hardness kernel and the Fukui
      function. In addition, the concept of the local hardness is analyzed in detail,
      and for the first time, profiles of local hardness with kinetic and exchange
      correlation contributions for polyatomic molecules are reported. Finally, the
      concept of condensed atomic hardness is introduced and its usefulness as chemical
      reactivity descriptor is examined.

PMID- 18044701
TI  - Relaxation of the mouse pubic symphysis during late pregnancy is not accompanied
      by the influx of granulocytes.
AB  - In some animals, such as mice and guinea pigs, a hormonally controlled mechanism
      increases the flexibility of the pubic symphysis and enhances the cervical
      remodeling necessary for safe delivery. Cervical ripening during pregnancy is
      associated with a paradoxical influx of leukocytes. However, the changes in cell
      metabolism during relaxation of the mouse pubic symphysis for delivery have not
      been extensively studied. In this work, we used light microscopy and transmission
      and scanning electron microcopy, as well as immunohistochemistry and Western
      blotting for MMP-8, to investigate the involvement of granulocytes or resident
      stromal cells in the relaxation of the virgin pubic symphysis during late
      pregnancy (days 18 and 19, before delivery) in vivo and in explanted joints. MMP
      8 was studied because this collagenase is a hallmark for cervical ripening
      associated with the influx of granulocytes during late pregnancy. Extensive
      dissolution and disorganization of the extracellular matrix was seen around
      fibroblastic-like cells in late pregnancy. In contrast to the cervix (positive
      control), morphological and immunohistochemical analyses revealed that there was
      no characteristic cellular inflammatory response in the interpubic tissue.
      Staining for MMP-8 was observed in chondroid and fibroblastic-like cells of
      virgin and relaxed interpubic ligament, respectively. However, no granulocytes
      were seen during the extensive remodeling of the pubic joint in late pregnancy.
      These results indicate that constitutive stromal cells may have an important role
      in tissue relaxation during remodeling of the pubic symphysis in pregnancy.

PMID- 18044702
TI  - Transcriptional regulation of mesencephalic dopaminergic neurons: the full circle
      of life and death.
AB  - Since mesencephalic dopaminergic neurons are associated to one of the most
      prominent human neurodegenerative ailments, Parkinson's disease, the molecular
      mechanism underlying their development and adult cellular properties has been the
      subject of intense investigations. Throughout life, transcription factors
      determine the fate of this neuronal population and control essential processes
      such as localization in the ventral midbrain, their neurotransmitter phenotype,
      their target innervations and synapse formation. Studies of transcription
      factors, such as Nurr1, Pitx3, Engrailed-1/2, and Lmx1a/b, have not only revealed
      importance of these genes during development, but also roles in the long-term
      survival and maintenance of these neurons. In this review, we will discuss the
      function of these transcription factors throughout the life of mesencephalic
      dopaminergic neurons and their value in the study of the disease mechanism.

PMID- 18044703
TI  - The arginine growth hormone stimulation test in bradykinetic-rigid parkinsonisms.
AB  - The arginine growth hormone (GH) stimulation test differentiates the Parkinsonian
      variant of multiple system atrophy (MSA-P) from idiopathic Parkinson's disease
      (PD). Our aim was to evaluate the accuracy of the arginine GH stimulation test in
      distinguishing between PSP, MSA-P, and PD. We measured the GH response to
      arginine in serum samples of 26 MSA-P, 23 PSP, and 26 PD patients, and in 80
      healthy controls. We used ANOVA followed by the Bonferroni test to compare GH
      values and peaks among groups. We used receiver operating characteristic curve
      analysis to establish the arginine cut-off level that best differentiated between
      MSA-P, PSP, and PD. The GH peak was significantly lower (P < 0.01) in MSA-P (1.46
      +/- 0.29 microg/L) than in both PD (8.74 +/- 0.98 microg/L) and PSP (6.64 +/-
      0.82 microg/L) patients, and controls (8.59 +/- 0.44 microg/L). Growth hormone
      peaked later in PSP patients than in PD patients and controls. At a cut-off level
      of 4 microg/L, arginine test distinguished MSA-P from PD with a sensitivity of
      92% and a specificity of 96%, and MSA-P from PSP with a sensitivity of 78% and a
      specificity of 96%. The GH response to arginine differentiates MSA-P from PD and
      PSP with a good diagnostic accuracy. The neuroendocrine response to arginine of
      PSP patients differed from that of MSA-P patients, but was not identical to that
      of normal controls and PD patients. Our results suggest that the impairment of
      the central mechanisms modulating GH release differs between PSP and MSA-P.

PMID- 18044704
TI  - The video images of sleep attacks in Parkinson's disease.
AB  - We describe a sleep attack, which was induced by taking excessive levodopa and
      pergolide, in a 73-year-old woman with Parkinson's disease. At the onset of the
      sleep attack, her head suddenly sagged and sometimes hit the table, but she did
      not notice these symptoms. Her family noticed that this sleep attack occurred
      when she began to speak slowly. Her family recorded this attack with a video
      camera. This sleep attack resolved with control of her medication. This is the
      first report of video images of a sleep attack due to excessive levodopa and a
      dopamine agonist.

PMID- 18044705
TI  - Ataxia and cerebellar atrophy--a novel manifestation of neuro-Behcet disease?

PMID- 18044707
TI  - Is basic research a good investment?

PMID- 18044706
TI  - Differential effects of levodopa and subthalamic nucleus deep brain stimulation
      on bradykinesia in Parkinson's disease.
AB  - Cardinal symptoms of Parkinson's disease (PD) respond well to treatment with
      levodopa and deep brain stimulation (DBS) of the subthalamic nucleus (STN).
      However, it has remained unclear whether levodopa and STN-DBS have differential
      effects on bradykinesia. We investigated 8 PD-patients with STN-electrodes in
      four conditions: STN-DBS and levodopa (ON(MED)/ON(STIM)), STN-DBS only
      (OFF(MED)/ON(STIM)), levodopa only (ON(MED)/OFF(STIM)), without STN-DBS/levodopa
      (OFF(MED)/OFF(STIM)). Fourteen volunteers served as controls. Subjects performed
      fastest possible (1) pronation/supination of the forearm (diadochokinesia) and
      (2) flexion and extension of the index finger (finger movements). Movements were
      recorded using a 3D-ultrasound-system. Maximum frequency, amplitude, and
      smoothness of movements were determined. During OFF(MED)/OFF(STIM), all
      parameters were worser than in all other conditions. In proximal diadochokinesia,
      OFF(MED)/ON(STIM) significantly improved the amplitude and frequency, whereas
      ON(MED)/OFF(STIM) had no significant effect. In contrast, we found a stronger
      effect of levodopa (ON(MED)/OFF(STIM)) on amplitudes of distal finger movement
      than on amplitudes of diadochokinesia. Combination of treatments during
      ON(MED)/ON(STIM) further improved both movements. However, maximum frequency
      remained lower in PD-patients during ON(MED)/ON(STIM) compared with controls.
      This study demonstrates a better effect of levodopa on distal finger movements
      and STN-DBS on proximal diadochokinesia. Furthermore, a complementary effect of
      both therapies on brain areas involved in bradykinesia can be assumed.

PMID- 18044708
TI  - Set-shifting and behavioral dysfunction in primary focal dystonia.
AB  - The occurrence of cognitive and behavioral symptoms in patients with primary
      dystonia remains a matter of debate. We compared 45 patients with primary
      dystonia with 27 control subjects for performance on neuropsychological tasks
      with a load on executive-Wisconsin Card Sorting Test (WCST) and Stroop test, and
      visuospatial-Benton's visual retention test (BVRT) and Block assembly test from
      Wechsler Adult Intelligence Scale BAT-functions, as well as for intensity of
      obsessive-compulsive symptoms (Yale Brown Obsessive Compulsive Scale, Y-BOCS).
      Correlation analysis was performed between neuropsychological performance,
      dystonia characteristics (duration, age of onset) and severity (Unified Dystonia
      Rating Scale, UDRS), and Y-BOCS. Patients made more perseverative errors on the
      WCST (P = 0.042) and had a higher mean Y-BOCS (P = 0.003) score than controls.
      Timed tests (BVRT, BAT, Stroop test) correlated with UDRS. Y-BOCS, WCST, and UDRS
      scores were not significantly correlated with one another.These results suggest
      that patients with primary dystonia may have set-shifting deficits and a higher
      intensity of obsessive compulsive symptoms when compared to healthy subjects.
      This may reflect a pattern of complex neurophysiological dysfunction involving
      dorsolateral, orbitofrontal, and motor frontostriatal circuits.

PMID- 18044709
TI  - Nonlinear imaging study of extracellular matrix in chemical-induced,
      developmental dissecting aortic aneurysm: evidence for defective collagen type
      III.
AB  - BACKGROUND: Using a recent model of dissecting aortic aneurysm (DAA) caused by in
      utero exposure to semicarbazide, we examined the elastin and collagen using
      standard methods and two nonlinear imaging techniques, multiphoton fluorescence
      (MPF) and second harmonic generation (SHG) microscopy. METHODS: Sprague-Dawley
      rat dams were given semicarbazide (6.13 mg/kg/day i.p.) from gestational days 14
      to 20 (GD14-20). Fetuses were harvested on GD20 and pups on postnatal day 1
      (PND1), PND7, and PND28; matched controls were from dams treated with saline.
      Aortic immunohistopathology and collagen/elastin signal intensity via MPF and SHG
      microscopy at an excitation wavelength of 800 nm were studied. RESULTS: Massive
      DAA of the aortic arch occurred in nearly 100% of pups at birth (i.e., no GD20
      fetuses showed lesions). MPF and SHG demonstrated that collagen was significantly
      degraded at GD20 and in newborns, but normalized by PND28. GD20 fetuses and
      newborn pups showed a decreased content of medial and adventitial collagen type
      III in pooled aortas by Western blot and immunohistochemistry. In 7- and 28-day
      old pups resolution of DAA blood in vascular media and a recovery of stainable
      collagen type III was found. Elastin in healed DAA (PND28 pups) was focally
      disorganized. CONCLUSION: MPF and SHG microscopy provide sensitive and high
      resolution information on aortic elastin and collagen. In this model of DAA,
      collagen displays aberrant imaging quality likely linked to a marked decrease in
      collagen type III in the developing extracellular matrix. Birth Defects Research
      (Part A) 2008.

PMID- 18044711
TI  - The use of a colon cancer associated nuclear antigen CCSA-2 for the blood based
      detection of colon cancer.
AB  - The early diagnosis of colorectal cancer (CRC) is central for effective
      treatment, as prognosis is directly related to the stage of the disease.
      Development of tumor markers found in the blood from patients, which can detect
      CRC at an early stage, should have a major impact in morbidity and mortality of
      this disease. The nuclear matrix is the structural scaffolding of the nucleus and
      specific nuclear matrix proteins (NMPs) have been identified as an "fingerprint"
      for various cancer types. Previous studies from our laboratory have identified
      four colon cancer associated NMPs termed colon cancer-specific antigen (CCSA)-2
      to (CCSA)-5. The objective of the present study was to analyze the expression of
      one of these proteins, CCSA-2 in serum from various patient populations and to
      determine whether CCSA-2 antibodies could be used in a clinically applicable
      serum-based immunoassay specifically to detect colon cancer. Using an indirect
      ELISA, which detects CCSA-2, the protein was measured in the serum from 174
      individuals, including healthy individuals, patients with colon cancer, patients
      with diverticulosis, colon polyps, inflammatory bowel disease (IBD) as well as
      other cancer types. With a predetermined cutoff absorbance of 0.6 OD we have
      successfully utilized this approach to develop an immunoassay that detected colon
      cancer. The immunoassay showed a sensitivity of 88.8% (24/27) and an overall
      specificity of 84.2% (106/127). This initial study showed the potential of CCSA-2
      to serve as a highly specific blood based marker for colon cancer. Although
      potentially promising, the results of this study must be confirmed in larger
      independent validation studies.

PMID- 18044710
TI  - ESE-1 is a potent repressor of type II collagen gene (COL2A1) transcription in
      human chondrocytes.
AB  - The epithelium-specific ETS (ESE)-1 transcription factor is induced in
      chondrocytes by interleukin-1beta (IL-1beta). We reported previously that early
      activation of EGR-1 by IL-1beta results in suppression of the proximal COL2A1
      promoter activity by displacement of Sp1 from GC boxes. Here we report that ESE-1
      is a potent transcriptional suppressor of COL2A1 promoter activity in
      chondrocytes and accounts for the sustained, NF-kappaB-dependent inhibition by IL
      1beta. Of the ETS factors tested, this response was specific to ESE-1, since ESE
      3, which was also induced by IL-1beta, suppressed COL2A1 promoter activity only
      weakly. In contrast, overexpression of ETS-1 increased COL2A1 promoter activity
      and blocked the inhibition by IL-1beta. These responses to ESE-1 and ETS-1 were
      confirmed using siRNA-ESE1 and siRNA-ETS1. In transient cotransfections, the
      inhibitory responses to ESE-1 and IL-1beta colocalized in the -577/-132 bp
      promoter region, ESE-1 bound specifically to tandem ETS sites at -403/-381 bp,
      and IL-1-induced binding of ESE-1 to the COL2A1 promoter was confirmed in vivo by
      ChIP. Our results indicate that ESE-1 serves a potent repressor function by
      interacting with at least two sites in the COL2A1 promoter. However, the
      endogenous response may depend upon the balance of other ETS factors such as ETS
      1, and other IL-1-induced factors, including EGR-1 at any given time.
      Intracellular ESE-1 staining in chondrocytes in cartilage from patients with
      osteoarthritis (OA), but not in normal cartilage, further suggests a fundamental
      role for ESE-1 in cartilage degeneration and suppression of repair.

PMID- 18044712
TI  - S100A8/A9, a key mediator for positive feedback growth stimulation of normal
      human keratinocytes.
AB  - S100A8 and S100A9 are known to be up-regulated in hyperproliferative and
      psoriatic epidermis, but their function in epidermal keratinocytes remains
      largely unknown. Here we show that (1) S100A8 and S100A9 are secreted by cultured
      normal human keratinocytes (NHK) in a cytokine-dependent manner, (2) when applied
      to NHK, recombinant S100A8/A9 (a 1:1 mixture of S100A8 and S100A9) induced
      expression of a number of cytokine genes such as IL-8/CXCL8, CXCL1, CXCL2, CXCL3,
      CCL20, IL-6, and TNFalpha that are known to be up-regulated in psoriatic
      epidermis, (3) the S100A8/A9-induced cytokines in turn enhanced production and
      secretion of S100A8 and S100A9 by NHK, and (4) S100A8 and S100A8/A9 stimulated
      the growth of NHK at a concentration as low as 1 ng/ml. These results indicate
      the presence of a positive feedback loop for growth stimulation involving
      S100A8/A9 and cytokines in human epidermal keratinocytes, implicating the
      relevance of the positive feedback loop to the etiology of hyperproliferative
      skin diseases, including psoriasis.

PMID- 18044713
TI  - Telomerase targeted oligonucleotide thio-phosphoramidates in T24-luc bladder
      cancer cells.
AB  - Bladder carcinoma is the second most common genitourinary malignancy. Treatment
      options for bladder cancer include surgery, combined with chemotherapy,
      radiation, and/or immunotherapy. The adjuvant chemotherapy and immunotherapy
      regimen have been widely used in locally invasive as well as metastatic disease.
      The evaluation of new active agents with improved tolerability has been the focus
      of investigations over the past decade with minimal overall improvements in
      outcomes. Telomerase activity has been found in approximately 85-90% of all human
      tumors, but not in the majority of adjacent normal tissues. This suggests that
      telomerase may be an attractive target for the development of novel anticancer
      therapeutic agents. GRN163L is a lipid conjugated oligonucleotide N3' --> P5'
      thio-phosphoramidate, and is a potent telomerase RNA (hTR) template antagonist.
      In the present study, we show that the telomerase activity of T24-luc bladder
      cancer cells is inhibited by 1 microM GRN163L within 24 h of incubation. After
      two weeks of exposure to GRN163L, T24-luc cells became "clustered" whereas non
      cancerous normal human uroepithelial cells were not morphologically affected.
      Moreover, in vitro GRN163L treated T24-luc bladder cancer cells entered G(0)/G(1)
      arrest following 2 weeks of continuous exposure and stopped dividing. Mismatch
      control compound had no effect on normal bladder epithelial cells or T24-luc
      cells. Additionally, a new generation of thio-phosphoramidate oligonucleotides
      were designed and tested in T24-luc cells and compared with GRN163L. The obtained
      results warrant further in vivo evaluation of GRN163L as a potential treatment
      for bladder cancer.

PMID- 18044714
TI  - Birth defects in uncles and aunts from Irish families with neural tube defects.
AB  - BACKGROUND: Previous studies suggested an excess of matrilineal cases of neural
      tube defects among distant relatives in NTD families. There is little information
      on patterns of heredity of other birth defects among distant relatives. METHODS:
      Between 1995 and 2003, 78 nuclear families and 373 uncles and aunts were
      interviewed about birth defects among uncles and aunts in Irish families with an
      NTD. RESULTS: Among 783 total uncles and aunts, those related through the mother
      had more birth defects overall than those related through the father (8.4 vs.
      4.0%, p = 0.01). The excess persisted after controlling with logistic regression
      models for maternal and paternal age, gender of uncle/aunt, proband's NTD
      diagnosis, and year of birth (OR 2.52; 95% CI: 1.29, 4.91; p = 0.007). Among
      individual birth defects, significant excesses over expected rates were seen for
      spina bifida, congenital heart defects, and syndactyly. CONCLUSIONS: This study
      of reported birth defects suggests that maternal uncles and aunts in Irish
      families have significantly more birth defects than paternal uncles and aunts.
      These results, if confirmed, support the hypothesis that NTD relatives carry a
      susceptibility to other birth defects, preferentially on the mother's side of the
      family, suggesting opportunities for prevention. Birth Defects Research (Part A)
      2008.

PMID- 18044715
TI  - Abnormal vibration-induced illusion of movement in idiopathic focal dystonia: an
      endophenotypic marker?
AB  - The frequency of symptomatic dystonia in relatives of patients with idiopathic
      focal dystonia (IFD) is higher than expected from epidemiologic studies implying
      that genetic factors may be involved. Perception of the vibration-induced
      illusion of movement (VIIM) is subnormal in patients with IFD compared with
      healthy volunteers and the abnormality corrects with volitional fatigue of the
      vibrated arm. The aim of the study was to establish the heritability of the
      abnormality of VIIM. The perception of illusion of movement elicited by vibration
      of the biceps brachii tendon before and after fatigue of the muscles was
      investigated in 30 patients with torticollis, 57 of their first degree relatives,
      and 19 healthy volunteers. VIIM did not change after fatigue in healthy controls.
      Before fatiguing the muscles, patients' perception of VIIM was less than healthy
      controls, (P < 0.01, unpaired t-test). After fatigue, the illusion of movement
      perceived by patients increased, so that it did not differ any more from that of
      the healthy control subjects (P < 0.05, repeated measures ANOVA). First degree
      relatives' response to vibration varied; 45% of parents, 60.7% of siblings, and
      63.6% of children had an "abnormal" response to vibration compared with 21% of
      healthy volunteers. In contrast to patients' response, the "abnormality" did not
      correct after volitional fatigue of the vibrated arm. The results suggest that
      abnormal VIIM may represent an endophenotypic marker for IFD, which interacts
      with other factors including central motor learning and compensation mechanisms
      in the expression of the dystonic phenotype.

PMID- 18044716
TI  - Calcium- and pH-dependent localization of annexin A6 isoforms in Balb/3T3
      fibroblasts reflecting their potential participation in vesicular transport.
AB  - Annexin A6 (AnxA6), calcium- and membrane-binding protein, is involved in
      membrane dynamics. It exists in the cell in two isoforms, AnxA6-1 and AnxA6-2,
      varying only by the VAAEIL sequence. In most cells, AnxA6-1 predominates. A
      limited number of observations suggests that both isoforms differ from each other
      functionally. The EGF-dependent Ca(2+) influx in A431 cells is inhibited only by
      AnxA6-1. Moreover, AnxA6-2 was found to exhibit higher affinity for Ca(2+). In
      this report we addressed the potential significance of the VAAEIL deletion in
      AnxA6-2. For this purpose, we expressed AnxA6 isoform cDNAs in bacteria or mouse
      Balb/3T3 fibroblasts. The recombinant AnxA6-2 was characterized by a less
      extended molecular shape than that of AnxA6-1 and required a narrower [Ca(2+)]
      range to bind liposomes. Upon lowering pH in the presence of EGTA recombinant
      AnxA6-2 became less hydrophobic than AnxA6-1 as revealed by the Triton X-114
      partition. Furthermore, AnxA6-2 revealed stronger F-actin binding than that of
      AnxA6-1. Immunofluorescence microscopy showed that the EGFP-tagged AnxA6 isoforms
      expressed in Balb/3T3 fibroblasts relocate in a Ca(2+)- and H(+)-sensitive manner
      to the vesicular structures in a perinuclear region or in cytosol. Cell
      fractionation showed that in resting conditions AnxA6-1 is associated with early
      endosomes and AnxA6-2 with late endosomes, and an increase in [Ca(2+)] and/or
      [H(+)] induced their opposite distribution. These findings suggest a potentially
      independent regulation, localization, and function of AnxA6 isoforms in Balb/3T3
      fibroblasts. More generally, our findings suggest distinct functions of AnxA6
      isoforms in membrane dynamics.

PMID- 18044717
TI  - Delayed-onset primary cytomegalovirus disease after liver transplantation.
AB  - Clinical practice guidelines recommend antiviral prophylaxis to cytomegalovirus
      (CMV) donor-positive/recipient-negative (D+/R-) liver transplant recipients. We
      assessed the outcome of this strategy by determining the incidence, clinical
      features, and risk factors of CMV disease among CMV D+/R- liver transplant
      recipients who received antiviral prophylaxis. Sixty-seven CMV D+/R- liver
      transplant recipients (mean age+/-standard deviation: 49.5+/-11.4 years; 75%
      male) received oral ganciclovir [n=9 (13%)] or valganciclovir [n=58 (87%)]
      prophylaxis for a median duration of 92 days (interquartile range: 91-100). No
      breakthrough CMV disease was observed during antiviral prophylaxis. However,
      primary CMV disease was observed in 2%, 25%, 27%, 27%, and 29% of patients at 1,
      3, 6, 12, and 24 months, respectively, after antiviral prophylaxis was stopped.
      The incidence of delayed-onset primary CMV disease was similar between those who
      received oral ganciclovir and valganciclovir. Nine (47%) patients had CMV
      syndrome, 8 (42%) had gastrointestinal CMV disease, and 2 (11%) had CMV
      hepatitis. Female patients (P=0.01) and younger age at transplant (P=0.03) were
      associated with an increased risk, whereas diabetes mellitus (P<0.001) was
      significantly associated with a lower risk of delayed-onset primary CMV disease.
      Allograft loss or mortality occurred in 8 (12%) patients during the median follow
      up period of 3.31 (range: 0.8-5.9) years. No significant association was observed
      between CMV disease and patient and allograft survival. In conclusion, CMV
      disease remains a common complication in CMV D+/R- liver transplant patients
      during the contemporary era of antiviral prophylaxis. Female patients and younger
      patients are at increased risk of delayed-onset primary CMV disease.

PMID- 18044718
TI  - Opposite effects of overexpressed myosin Va or heavy meromyosin Va on vesicle
      distribution, cytoskeleton organization, and cell motility in nonmuscle cells.
AB  - Myosin Va, an actin-based motor protein that transports intracellular cargos, can
      bundle actin in vitro. Whether myosin Va regulates cellular actin dynamics or
      cell migration remains unclear. To address this, we compared Chinese Hamster
      Ovary (CHO) cells that stably express GFP fused to either full length mouse
      myosin Va (GFP-M5) or heavy meromyosin Va (GFP-M5Delta). GFP-M5 and GFP-M5Delta
      co-immunoprecipitate with CHO myosin Va and serve as overexpression of wild-type
      and dominant negative mutants of myosin Va. Compared to non-expressing control
      cells, GFP-M5-overexpressing cells have peripheral endocytic vesicles, spread
      slowly after plating, as well as produce robust interior actin stress fibers,
      myosin II bundles, and focal adhesions. However, these cells display normal cell
      migration and lamellipodial dynamics. In contrast, GFP-M5Delta-expressing cells
      have perinuclear endocytic vesicles, produce thin interior actin and myosin
      bundles and contain no interior focal adhesions. In addition, these cells spread
      rapidly, migrate slowly and display reduced lamellipodial dynamics. Similarly,
      neurite outgrowth is compromised in neurons cultured from transgenic Drosophila
      that express M5Delta-dsRed and in neurons cultured from Drosophila that produce a
      tailless version of endogenous myosin V. Together, these data suggest that myosin
      Va overexpression induces actin bundles in vivo whereas the tailless version
      fails to bundle actin and disrupts cell motility.

PMID- 18044719
TI  - SIRT2, tubulin deacetylation, and oligodendroglia differentiation.
AB  - The mammalian silent information regulator 2 (SIRT2) is an NAD-dependent histone
      deacetylase with known roles in the regulation of the cell cycle. SIRT2 is also a
      tubulin deacetylase functioning as an early mitotic checkpoint, but its roles in
      regulating cytoplasmic microtubule dynamics were unknown. Novel findings now
      indicate that SIRT2 is specifically enriched in brain oligodendroglia, where it
      functions specifically in modulating the oligodendrocyte cytoskeleton during its
      differentiation and maturation.

PMID- 18044720
TI  - Flow cytometry measurement of the labile iron pool in human hematopoietic cells.
AB  - Iron is important for many biological processes, and its deficiency or excess is
      involved in pathological conditions. Although most iron is firmly bound (e.g., in
      hemoglobin), some, the labile iron pool (LIP), is bound to low-affinity ligands.
      The level of LIP is regulated to meet the cell's requirements for iron but
      prevent excess. We describe herein a multiparameter flow cytometry procedure for
      measuring LIP in various human hematopoietic cells. Peripheral blood and bone
      marrow (BM) cells were loaded with calcein-AM, washed, and then incubated with or
      without the high-affinity iron-chelator Deferiprone (L1). Specific cell
      subpopulations were identified based on side-light scattering and expression of
      surface antigens. LIP was determined based on the ability of L1 to bind and
      remove iron from calcein and thereby increase the fluorescence emitted by the
      cells. Blood cells differ in their LIP content in the order monocytes > PMN > RBC
      > lymphocytes. Analysis of BM cells indicated a similar tendency among precursors
      of the different lineages. The results also showed that among myeloid precursors,
      LIP increases along cell maturation. Flow cytometry might be useful for
      evaluating LIP in various diseases and for studying the efficacy of iron
      chelators.

PMID- 18044721
TI  - Rapid, high throughput determination of cervical cytology specimen adequacy using
      a capillary-based cytometer.
AB  - Despite the fact that compact instruments dedicated to counting cells are readily
      available especially in hematology, liquid-based cervical cytology specimen
      adequacy is still determined by pathologist review following the preparation of
      slides. More than 100 liquid-based cervical cytology specimens collected in
      ThinPrep vials were processed into slides for diagnosis and assessment of
      specimen adequacy using the Bethesda 2001 criteria. Residual liquid (100 muL) was
      transferred to a single well of a 96-well plate and run in a capillary cytometer
      (Guava Technologies, Hayward, CA) with forward scatter and side scatter
      detectors. We determined that the sensitivity and specificity of this assay for
      unsatisfactory samples was 100% and 97%, respectively, compared with
      cytopathologic examination. The difference in the concentration of ectocervical
      cells/muL (EPU) between samples determined to be unsatisfactory by virtue of less
      than an estimated 5,000 cells per slide and satisfactory samples were
      statistically significant (P< 0.001). Here, we report the use of this rapid
      specimen adequacy assay on a small, capillary based, personal cytometer. Use of
      this instrument reduced the amount of sample required by >90% and reduced the
      average per sample assay time from 120 s to 10 s compared with flow cytometry.

PMID- 18044722
TI  - Nuclear protein contents in peripheral blood mononuclear cells of trisomy 21
      infants.
AB  - OBJECTIVE: The trisomy 21 (Ts21) or Down's syndrome (DS) phenotype is assumed to
      occur primarily by the expression/overexpression of some genes encoded by the
      extra chromosome 21. It has recently been shown by AgNOR staining that babies
      with Ts21 have more AgNOR area (more NOR proteins) and more RNA content in their
      peripheral blood mononuclear cells (PBMCs) than those of controls. The aim of
      this study was to test whether or not the nuclear proteins content of PBMCs from
      trisomy 21 babies/infants is higher than that of the controls. METHOD: For this
      purpose, flow cytometric measurement of the stained PBMC nuclei was used. Nuclei
      from PBMCs was isolated and stained with propidium iodide and fluorescein
      isothiocyanate (PI/FITC) for DNA and protein estimation, respectively. RESULTS:
      Mean nuclear protein content of Ts21's (N = 30, mean age = 3.46 +/- 3.05 years
      old) PBMCs was found statistically higher than that of the controls (N = 33, mean
      age = 3.79 +/- 1.93 years old) (P = 0.005, nonparametric Mann-Whitney U test for
      two independent variables). This means that the average nuclear protein content
      of PBMC from Ts21 infants is higher than that of the controls. Furthermore, there
      is a moderate negative correlation between the ages of the studied DS patients
      and the protein content in the nuclei of their PBMCs (Linear regression analysis:
      P = 0.002, r = -0.55). This correlation is not found with controls (P = 0.186, r
      = -0.24). CONCLUSION: We have concluded that average protein content of PBMCs'
      nuclei from DS infants is higher than that of the controls, decreasing
      significantly with age.

PMID- 18044723
TI  - DNA ploidy and cell cycle analyses in the bone marrow cells of patients with
      megaloblastic anemia using laser scanning cytometry.
AB  - BACKGROUND: Megaloblastic anemias are characterized by several hematopoietic
      cells with dysplastic nuclear morphology. The analyses of DNA ploidy and cell
      cycle of these cells are important to understand the property of such diseases.
      METHODS: As laser scanning cytometry (LSC) is a useful tool to evaluate the
      morphology of the cells fixed on the slide glass together with the quantitative
      analysis of the fluorescence information of each cell by rapid scanning of the
      specimens, the authors examined the DNA ploidy and cell cycle of six cases with
      megaloblastic anemia using LSC. RESULTS: Giant neutrophilic series such as giant
      metamyelocytes and giant band cells were found to have extraordinarily higher DNA
      ploidy, while hypersegmented neutrophils represented the normal diploid pattern
      like normal neutrophils. As to megaloblasts, cell cycle analysis showed that the
      proportion of the cells in S phase was increased as compared with the case of
      normal erythroblasts. CONCLUSIONS: The present study clearly demonstrates the
      abnormal aspects of the hematopoietic cells with megaloblastic anemia from the
      viewpoint of the DNA ploidy and cell cycle analyzed by the use of LSC.

PMID- 18044724
TI  - Selection for resistance to methoxyfenozide and 20-hydroxyecdysone in cells of
      the beet armyworm, Spodoptera exigua.
AB  - In this report with an ecdysteroid-responsive cell line of the beet armyworm,
      Spodoptera exigua (Se4) selection for resistance against methoxyfenozide and the
      insect moulting hormone (20-hydroxyecdysone, 20E) was carried out to analyze the
      resulting resistant cells in order to elucidate possible mechanisms of resistance
      towards these compounds. From these cultures, five methoxyfenozide- and four 20E
      resistant subclones were selected starting from 0.1 nM methoxyfenozide up to 100
      microM and from 10 nM 20E up to 100 microM, respectively. To date, the selected
      cells kept their loss of susceptibility for 100 microM. Here we evaluated two
      processes known to be important in insecticide resistance, namely metabolism and
      pharmacokinetics, in the selected methoxyfenozide- and 20E-resistant subclones.
      Synergism experiments with piperonyl butoxide, S,S,S-tributyl
      phosphorotrithioate, and diethyl maleate, which are respective inhibitors of
      monooxygenases, esterases, and gluthation-S-transferases, did not affect the
      level of the resistance. To check the possible existence of active transport in
      the resistant cells, we used ouabain, an inhibitor of active membrane transport.
      In parallel, the absorption profile was studied in resistant and susceptible
      cells with use of 14C-methoxyfenozide. Interestingly, resistant subclones showed
      cross-resistance towards methoxyfenozide and 20E. The resistance was irreversible
      even after the compounds were removed from the medium.

PMID- 18044725
TI  - Novel GCH1 mutation in a Brazilian family with dopa-responsive dystonia.
AB  - Dopa responsive Dystonia (DRD) was first described in 1971 and typically begins
      at childhood with gait dysfunction caused by foot dystonia progressing to affect
      other extremities. There is marked diurnal fluctuation and sustained improvement
      of symptoms with low dose levodopa therapy. Heterozygous mutation of the gene
      GCH1 has been shown to cause DRD. We studied GCH1 in nine patients with DRD from
      six families of Federal University of Minas Gerais Movement Disorders Clinic. We
      identified three mutations; two affected siblings carried a novel T209P mutation
      and two siblings from another family were compound heterozygous carriers of
      Met211Val and Lys224Arg mutations. To our knowledge this is the first report of
      GCH1 mutations underlying DRD in patients from Brazil.

PMID- 18044726
TI  - Discordance between measured postural instability and absence of clinical
      symptoms in Parkinson's disease patients in the early stages of the disease.
AB  - We compared postural performances in early stage Parkinson's disease (PD)
      patients and healthy subjects, and to determine if PD patients have infraclinical
      postural instability. Nine PD patients and 18 age- and sex-matched control
      subjects were recorded with open eyes (OE) and closed eyes (CE) using a force
      platform in static and dynamic conditions with a mobile platform allowing antero
      posterior and medio lateral oscillations. Oscillations of the mobile platform and
      balance strategy were quantified using both a force platform and the Vicon
      system. Under static conditions with both OE and CE, PD patients had a larger
      center foot pressure sway area than the control subjects (P = 0.007 and P = 0.04,
      respectively). Under dynamic conditions, the PD patients' sway area was greater
      than that of the control subjects in the CE antero posterior position (P = 0.04).
      Oscillations of the mobile platform were not different between the two groups.
      Lastly, all subjects used an ankle strategy, but PD patients had larger head
      oscillations than the control subjects. Early stage PD patients have an
      infraclinical postural instability which is compensated when it is more difficult
      to maintain good balance, suggesting that the neurological mechanisms of balance
      are partially still operating at this stage of the disease.

PMID- 18044727
TI  - Survival in multiple system atrophy.
AB  - We here report survival in patients with multiple system atrophy (MSA) in a
      large, prospectively studied group of patients with MSA. Eighty-five of 100
      patients were known to have died. Three patients were rediagnosed as having PD.
      Twenty-four patients came to autopsy, which showed MSA in 22 and idiopathic
      Parkinson's disease in 2. The median survival time was 8.6 and 7.3 years for men
      and women, respectively (hazard ratio for women was 1.49, 95% CI 0.97-2.31, P =
      0.07). Except for rediagnosis as PD, no predictive factors for better survival
      could be identified. These data confirm the relatively poor prognosis of MSA of
      less than 9 years on average.

PMID- 18044728
TI  - A randomized controlled trial of late conversion from calcineurin inhibitor (CNI)
      based to sirolimus-based immunosuppression in liver transplant recipients with
      impaired renal function.
AB  - Renal impairment is common in patients after liver transplantation and is
      attributable in large part to the use of calcineurin inhibitor (CNI)-based
      immunosuppression. We sought to determine whether conversion to sirolimus-based
      immunosuppression was associated with improved renal function. In a single
      center, randomized, controlled trial, 30 patients at least 6 months post liver
      transplantation were randomized to remain on CNI-based immunosuppression or to
      switch to sirolimus-based immunosuppression. The primary outcome measure was
      change in measured glomerular filtration rate (GFR) between baseline and 12
      months. Of 30 patients randomized, 3 were withdrawn at randomization, leaving 14
      patients on CNI and 13 on sirolimus. There was a significant improvement in delta
      GFR following conversion to sirolimus at 3 months (7.7 mL/minute/1.73 m2; 95%
      confidence interval, 3.5-11.9) and 1 yr (6.1 mL/minute/1.73 m2; 95% confidence
      interval, 0.9-11.4). The difference in absolute GFR between the 2 study groups
      was significant at 3 months (P=0.02), but not at 12 months (P=0.07). The
      principal adverse events following conversion were the development of skin rash
      (9 of 13 patients, 69%) and mouth ulcers (5 of 13 patients, 38%). Two patients
      developed acute rejection at 2 and 3 months following conversion, 1 in
      association with low sirolimus levels and 1 having stopped the drug
      inadvertently. In conclusion, overall, this study suggests that conversion to
      sirolimus immunosuppression is associated with a modest improvement in renal
      function. Side effects were common, but tolerable in most patients and controlled
      with dose reduction.

PMID- 18044729
TI  - Prostate-specific antigen levels in relation to cadmium exposure and zinc intake:
      results from the 2001-2002 National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Cadmium exposure has been suggested as a risk factor for prostate
      cancer, and experimental literature suggests that the carcinogenic effect of
      cadmium is modified by the presence of zinc. We evaluated total prostate-specific
      antigen (PSA) levels in relation to urinary cadmium concentrations and dietary
      zinc intake. METHODS: PSA levels were determined in 1,320 men over the age of 40
      in the 2001-2002 National Health and Nutrition Examination Survey (NHANES).
      Urinary cadmium concentrations were measured in about one-third of the sample
      population, whereas dietary zinc intake was based on participants' 24-hr recall.
      Information on all three variables was available for 422 men in the 2001-2002
      NHANES survey. We performed linear regressions to evaluate the relationships
      these factors after accounting for age and other covariates. RESULTS: Little
      evidence for an association between cadmium and elevated PSA level was observed.
      However, the data provide suggestive evidence for an interaction between zinc
      intake and cadmium exposure (P for interaction=0.09). Among men with zinc intake
      less than the median level of 12.67 mg/day, an increase in 1 microg/g creatinine
      cadmium exposure was associated with a 35% increase in PSA level. In contrast,
      among men with greater than median zinc intake, little evidence for an
      association between cadmium and PSA was found. CONCLUSIONS: These findings
      suggest a protective effect of zinc intake on cadmium-induced prostatic injury,
      and may provide further rationale for investigating the impact of these factors
      individually and jointly on the etiology of prostate cancer.

PMID- 18044730
TI  - Deletion of PSCA increases metastasis of TRAMP-induced prostate tumors without
      altering primary tumor formation.
AB  - BACKGROUND: Prostate stem cell antigen (PSCA) is expressed in normal epithelium
      of various tissues, in embryos and adult animals. PSCA expression is upregulated
      in up to 70% of prostate tumors and metastases, and a subset of bladder and
      pancreatic cancers. However, its function is unknown. We studied the effect of
      targeted gene deletion of PSCA on normal organ development and prostate
      carcinogenesis. METHODS: PSCA +/+, PSCA +/-, and PSCA -/- mice were bred and aged
      to 22 months. A cohort of animals was treated with gamma-irradiation at 2 and 6
      months of age. PSCA knockout mice were crossed to TRAMP mice and TRAMP+ PSCA +/+,
      TRAMP+ PSCA +/-, and TRAMP+ PSCA -/- mice and offspring aged to 10 months of age.
      Tissues were analyzed by RT-PCR, histology, and immunohistochemistry for markers
      of proliferation, apoptosis, angiogenesis, and tumor progression. RESULTS: PSCA
      knockout animals were viable, fertile and indistinguishable from wild-type
      littermates. Spontaneous or radiation-induced primary epithelial tumor formation
      was also similar in wild-type and PSCA knockout mice. We observed an increased
      frequency of metastasis in TRAMP+ PSCA heterozygous and knockout mice, compared
      to TRAMP+ wild-type mice. Metastases were largely negative for PSCA and androgen
      receptor. Cleaved-caspase 3 and CD31 staining was similar in all genotypes.
      Aurora-A and Aurora-B kinases were detected in the cytoplasm of PSCA heterozygous
      and knockout tumors, suggesting aberrant kinase function. CONCLUSION: These data
      suggest that PSCA may play a role in limiting tumor progression in certain
      contexts, and deletion of PSCA may promote tumor migration and metastasis.

PMID- 18044731
TI  - Anti-PSMA immunotoxin as novel treatment for prostate cancer? High and specific
      antitumor activity on human prostate xenograft tumors in SCID mice.
AB  - BACKGROUND: Expression of the prostate specific membrane antigen (PSMA) is highly
      restricted to prostate epithelial cells. Therefore, toxin-based immunotherapy
      against this antigen may represent an alternative therapeutic option for prostate
      cancer. For these purposes, the effects of the recombinant anti-PSMA immunotoxin
      A5-PE40 on prostate tumor growth were investigated in vitro and in vivo. METHODS:
      The in vitro binding and cytotoxicity of A5-PE40 were tested on the PSMA
      expressing prostate cancer cell line C4-2 and on the PSMA-negative cell line
      DU145 by flow cytometry and WST assays. The binding of the immunotoxin to SCID
      mouse xenografts and to various mouse organs was examined by Western blot
      analysis. In vivo, the antitumor activity of the immunotoxin was tested by
      injecting A5-PE40 in mice bearing C4-2 or DU145 xenografts. RESULTS: In vitro, a
      specific binding of A5-PE40 to C4-2 cells could be shown with a concentration
      dependent cytotoxicity (IC(50) value=220 pM). In the next step, a specific
      binding of the immunotoxin to C4-2 xenografts could be demonstrated. In contrast,
      no binding on mouse organs expressing high homologous mouse PSMA was found. The
      treatment of mice with C4-2 tumors caused a significant inhibition of tumor
      growth in vivo, whereas DU145 xenografts remained totally unaffected.
      CONCLUSIONS: A5-PE40 represents a recombinant anti-PSMA immunotoxin with potent
      antitumor activity in mice bearing human prostate cancer xenograft tumors.
      Therefore, A5-PE40 could be a promising candidate for therapeutic applications in
      patients with prostate cancer.

PMID- 18044732
TI  - Hox genes and the regulation of movement in Drosophila.
AB  - Many animals show regionally specialized patterns of movement along the body
      axis. In vertebrates, spinal networks regulate locomotion, while the brainstem
      controls movements of respiration and feeding. Similarly, amongst invertebrates
      diversification of appendages along the body axis is tied to the performance of
      characteristically different movements such as those required for feeding,
      locomotion, and respiration. Such movements require locally specialized networks
      of nerves and muscles. Here we use the regionally differentiated movements of
      larval crawling in Drosophila to investigate how the formation of a locally
      specialized locomotor network is genetically determined. By loss and gain of
      function experiments we show that particular Hox gene functions are necessary and
      sufficient to dictate the formation of a neuromuscular network that orchestrates
      the movements of peristaltic locomotion.

PMID- 18044733
TI  - Ultrastructural analysis of chemical synapses and gap junctions between
      Drosophila brain neurons in culture.
AB  - Dissociated cultures from many species have been important tools for exploring
      factors that regulate structure and function of central neuronal synapses. We
      have previously shown that cells harvested from brains of late stage Drosophila
      pupae can regenerate their processes in vitro. Electrophysiological recordings
      demonstrate the formation of functional synaptic connections as early as 3 days
      in vitro (DIV), but no information about synapse structure is available. Here, we
      report that antibodies against pre-synaptic proteins Synapsin and Bruchpilot
      result in punctate staining of regenerating neurites. Puncta density increases as
      neuritic plexuses develop over the first 4 DIV. Electron microscopy reveals that
      closely apposed neurites can form chemical synapses with both pre- and
      postsynaptic specializations characteristic of many inter-neuronal synapses in
      the adult brain. Chemical synapses in culture are restricted to neuritic
      processes and some neurite pairs form reciprocal synapses. GABAergic synapses
      have a significantly higher percentage of clear core versus granular vesicles
      than non-GABA synapses. Gap junction profiles, some adjacent to chemical
      synapses, suggest that neurons in culture can form purely electrical as well as
      mixed synapses, as they do in the brain. However, unlike adult brain, gap
      junctions in culture form between neuronal somata as well as neurites, suggesting
      soma ensheathing glia, largely absent in culture, regulate gap junction location
      in vivo. Thus pupal brain cultures, which support formation of interneuronal
      synapses with structural features similar to synapses in adult brain, are a
      useful model system for identifying intrinsic and extrinsic regulators of central
      synapse structure as well as function.

PMID- 18044734
TI  - Cooperative activity of multiple upper layer proteins for thalamocortical axon
      growth.
AB  - During development, sensory thalamocortical (TC) axons grow into the neocortex
      and terminate primarily in layer 4. To study the molecular mechanism that
      underlies lamina-specific TC axon termination, we investigated the responsiveness
      of TC axons to ephrin-A5, semaphorin-7A (Sema7A) and kit ligand (KL), which are
      expressed in the upper layers of the developing cortex. Dissociated cells of the
      dorsal thalamus from embryonic rat brain were cultured on dishes that were coated
      with preclustered Fc-tagged extracellular domains of these molecules. Each
      protein was found to promote TC axon growth in a dose-dependent fashion of a bell
      shaped curve. Any combination of the three proteins showed a cooperative effect
      in lower concentrations but not in higher concentrations, suggesting that their
      growth-promoting activities act in a common pathway. The effect of spatial
      distributions of these proteins was further tested on a filter membrane, in which
      these proteins were printed at a size that recapitulates the scale of laminar
      thickness in vivo, using a novel protein-printing technique, Simple-To-mAke
      Micropore Protein-Printing (STAMP2) method. The results demonstrated that TC
      axons grew massively on the laminin-coated region but were prevented from
      invading the adjacent ephrin-A5-printed region, suggesting that TC axons detect
      relative differences in the growth effect between these regions. Moreover, the
      inhibitory action of ephrin-A5 was enhanced by copresence with KL and Sema7A.
      Together, these results suggest that the lamina-specific TC axon targeting
      mechanism involves growth-inhibitory activity by multiple molecules in the upper
      layers and detection in the molecular environments between the upper and deep
      layers.

PMID- 18044735
TI  - Nitric oxide regulates axonal regeneration in an insect embryonic CNS.
AB  - In higher vertebrates, the central nervous system (CNS) is unable to regenerate
      after injury, at least partially because of growth-inhibiting factors.
      Invertebrates lack many of these negative regulators, allowing us to study the
      positive factors in isolation. One possible molecular player in neuronal
      regeneration is the nitric oxide (NO)-cyclic guanosine-monophosphate (cGMP)
      transduction pathway which is known to regulate axonal growth and neural
      migration. Here, we present an experimental model in which we study the effect of
      NO on CNS regeneration in flat-fillet locust embryo preparations in culture after
      crushing the connectives between abdominal ganglia. Using whole-mount
      immunofluorescence, we examine the morphology of identified serotonergic neurons,
      which send a total of four axons through these connectives. After injury, these
      axons grow out again and reach the neighboring ganglion within 4 days in culture.
      We quantify the number of regenerating axons within this period and test the
      effect of drugs that interfere with NO action. Application of exogenous NO or
      cGMP promotes axonal regeneration, whereas scavenging NO or inhibition of soluble
      guanylyl cyclase delays regeneration, an effect that can be rescued by
      application of external cGMP. NO-induced cGMP immunostaining confirms the
      serotonergic neurons as direct targets for NO. Putative sources of NO are
      resolved using the NADPH-diaphorase technique. We conclude that NO/cGMP promotes
      outgrowth of regenerating axons in an insect embryo, and that such embryo-culture
      systems are useful tools for studying CNS regeneration.

PMID- 18044736
TI  - Patent foramen ovale and unexplained ischemic cerebrovascular events in children.
AB  - OBJECTIVES: To consider the role of patent foramen ovale (PFO) in ischemic
      cerebrovascular event of unknown cause in children. BACKGROUND: Data regarding
      the possibility of paradoxical embolism in unexplained ischemic cerebrovascular
      event in children are lacking. METHODS: Between January 2005 and March 2007, all
      consecutive children evaluated due to ischemic cerebrovascular event were
      included in the retrospective study. In addition to the standard diagnostic
      protocol, a contrast transcranial Doppler (TCD) with Valsalva maneuver (VM) was
      performed in patients with unexplained events. Percutaneous PFO closure was
      offered to all patients with ischemic cerebrovascular event of unknown cause and
      presumed paradoxical embolism. RESULTS: Eighteen patients aged between 2 and 17
      years (median 11.5 years) were included in the study: 12 patients suffered
      ischemic stroke and six with transient ischemic attack (TIA). In six patients,
      ischemic stroke was of unknown cause and contrast TCD with VM was positive in
      four of them. In addition, TCD study was positive in five patients evaluated
      because of TIA. Nine patients with presumed paradoxical embolism underwent an
      attempt at the percutaneous PFO closure. CONCLUSIONS: It appears that the role of
      PFO in ischemic cerebrovascular event of unknown cause in children may be
      underestimated. Contrast TCD with VM is a sensitive, noninvasive method for PFO
      detection, proved in our experience particularly suitable for children. In
      children with unexplained ischemic cerebrovascular event and presumed paradoxical
      embolism, percutaneous PFO closure should be considered.

PMID- 18044737
TI  - Cognitive impairment in rats after long-term exposure to GSM-900 mobile phone
      radiation.
AB  - Considering the frequent use of mobile phones, we have directed attention to
      possible implications on cognitive functions. In this study we investigated in a
      rat model the long-term effects of protracted exposure to Global System for
      Mobile Communication-900 MHz (GSM-900) radiation. Out of a total of 56 rats, 32
      were exposed for 2 h each week for 55 weeks to radio-frequency electromagnetic
      radiation at different SAR levels (0.6 and 60 mW/kg at the initiation of the
      experimental period) emitted by a (GSM-900) test phone. Sixteen animals were sham
      exposed and eight animals were cage controls, which never left the animal house.
      After this protracted exposure, GSM-900 exposed rats were compared to sham
      exposed controls. Effects on exploratory behaviour were evaluated in the open
      field test, in which no difference was seen. Effects on cognitive functions were
      evaluated in the episodic-like memory test. In our study, GSM exposed rats had
      impaired memory for objects and their temporal order of presentation, compared to
      sham exposed controls (P = 0.02). Detecting the place in which an object was
      presented was not affected by GSM exposure. Our results suggest significantly
      reduced memory functions in rats after GSM microwave exposure (P = 0.02).

PMID- 18044738
TI  - Anti-inflammatory effects of low-intensity extremely high-frequency
      electromagnetic radiation: frequency and power dependence.
AB  - Using a model of acute zymosan-induced footpad edema in NMRI mice, the frequency
      and power dependence of anti-inflammatory effect of low-intensity extremely high
      frequency electromagnetic radiation (EHF EMR) was found. Single whole-body
      exposure of animals to EHF EMR at the intensity of 0.1 mW/cm(2) for 20 min at 1 h
      after zymosan injection reduced both the footpad edema and local hyperthermia on
      average by 20% at the frequencies of 42.2, 51.8, and 65 GHz. Some other
      frequencies from the frequency range of 37.5-70 GHz were less effective or not
      effective at all. At fixed frequency of 42.2 GHz and intensity of 0.1 mW/cm(2),
      the effect had bell-shaped dependence on exposure duration with a maximum at 20
      40 min. Reduction of intensity to 0.01 mW/cm(2) resulted in a change of the
      effect dependence on exposure duration to a linear one. Combined action of
      cyclooxygenase inhibitor sodium diclofenac and EHF EMR exposure caused a partial
      additive effect of decrease in footpad edema. Combined action of antihistamine
      clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti
      inflammatory effect of EHF EMR. The results obtained suggest that arachidonic
      acid metabolites and histamine are involved in realization of anti-inflammatory
      effects of low-intensity EHF EMR.

PMID- 18044739
TI  - Setup and dosimetry for exposure of human skin in vivo to RF-EMF at 900 MHz.
AB  - The aim of this study was a dosimetrical analysis of an experimental setup used
      in the exposure of 10 female volunteers to GSM 900 radiation. The exposure was
      carried out by irradiating a small region of the right forearms of the volunteers
      for 1 h, after which biopsies were taken from the exposed skin for protein
      analysis. The source of irradiation was a half-wave dipole fed with a computer
      controlled GSM phone. The specific absorption rate (SAR) induced in the skin
      biopsy was assessed by computer simulations. The numerical model of the arm
      consisted of a muscle tissue simulating cylinder covered with thin skin (1 mm)
      and fat (3 mm) layers. The simulation models were validated by measurements with
      a homogeneous cylindrical liquid phantom. The average SAR value in the biopsy was
      1.3 W/kg and the estimated uncertainty +/-20% (K = 2). The main source of error
      was found to be variations in the distance of the forearm from the dipole (10 +/-
      1 mm). Other significant sources of uncertainty are individual variations of the
      fat layer and arm thicknesses, and the uncertainty of radio frequency (RF) power
      measurement.

PMID- 18044740
TI  - The effects of 884 MHz GSM wireless communication signals on headache and other
      symptoms: an experimental provocation study.
AB  - Findings from prior studies of possible health and physiological effects from
      mobile phone use have been inconsistent. Exposure periods in provocation studies
      have been rather short and personal characteristics of the participants poorly
      defined. We studied the effect of radiofrequency field (RF) on self-reported
      symptoms and detection of fields after a prolonged exposure time and with a well
      defined study group including subjects reporting symptoms attributed to mobile
      phone use. The design was a double blind, cross-over provocation study testing a
      3-h long GSM handset exposure versus sham. The study group was 71 subjects age 18
      45, including 38 subjects reporting headache or vertigo in relation to mobile
      phone use (symptom group) and 33 non-symptomatic subjects. Symptoms were scored
      on a 7-point Likert scale before, after 1(1/2) and 2(3/4) h of exposure. Subjects
      reported their belief of actual exposure status. The results showed that headache
      was more commonly reported after RF exposure than sham, mainly due to an increase
      in the non-symptom group. Neither group could detect RF exposure better than by
      chance. A belief that the RF exposure had been active was associated with skin
      symptoms. The higher prevalence of headache in the non-symptom group towards the
      end of RF exposure justifies further investigation of possible physiological
      correlates. The current study indicates a need to better characterize study
      participants in mobile phone exposure studies and differences between symptom and
      non-symptom groups.

PMID- 18044741
TI  - Indoor transformer stations as predictors of residential ELF magnetic field
      exposure.
AB  - Transformer stations in apartment buildings may offer a possibility to conduct
      epidemiological studies that involve high exposure to extremely low frequency
      magnetic fields (MF), avoid selection bias and minimize confounding factors. To
      validate exposure assessment based on transformer stations, measurements were
      performed in thirty buildings in three Finnish cities. In each building, spot
      measurements in all rooms and a 24-h recording in a bedroom were performed in one
      apartment above a transformer station (AAT), in one first floor (FF) reference
      apartment, and one reference apartment on upper floors (UF). The apartment mean
      of spot measurements was 0.62 microT in the AATs, 0.21 microT in the FF and 0.11
      microT in the UF reference apartments The 24-h apartment mean (estimated from the
      spot measurements and the bedroom 24-h recording) was 0.2 microT or higher in 29
      (97%) AATs, in 7 (25%) FF and in 3 (10 %) UF reference apartments. The
      corresponding numbers for the 0.4 microT cut-off point were 19 (63%), 4 (14%),
      and 1 (3.3%). The higher MF level in the FF reference apartments indicates that
      they should not be considered "unexposed" in epidemiological studies. If such
      apartments are excluded, a transformer station under the floor predicts 24-h
      apartment mean MF with a sensitivity of 0.41 (or 0.58) and a specificity of 0.997
      (or 0.97), depending on the MF cut-off point (0.2 or 0.4 microT). The results
      indicate that apartments can be reliably classified as high and low MF field
      categories based on the known location of transformer stations.

PMID- 18044742
TI  - Visualization of shell matrix proteins in hemocytes and tissues of the Eastern
      oyster, Crassostrea virginica.
AB  - The tissues of the oyster were examined for the presence of shell matrix proteins
      (SMPs) using a combination of Western, proteomic, and epi-fluorescent microscopy
      techniques. SMP, including 48 and 55 kDa phosphoproteins, was detected in the
      epithelial cells of mantle, gill, heart, and adductor muscle and linings of
      arteries and veins. The 48 kDa SMP circulates continuously within the hemolymph,
      and is present in the immune system hemocytes. It appears to be secreted from
      hemocytes on induction of shell repair. We suggest that the 48 and 55 kDa
      proteins are multifunctional and bridge the process of soft tissue repair and
      shell formation by mediating cellular activities during immune response as well
      as interacting with the mineral phase during deposition.

PMID- 18044743
TI  - Intravenous interferon during the anhepatic phase of liver retransplantation and
      prevention of recurrence of cholestatic hepatitis C virus.
AB  - Cholestatic hepatitis C virus (HCV) infection post orthotopic liver
      transplantation is associated with a poor prognosis. We describe 2 patients who
      received interferon and ribavirin for cholestatic HCV infection with clearance of
      HCV RNA from the serum. Both developed signs of graft failure necessitating
      repeat orthotopic liver transplantation, and at surgery, interferon was
      administered during the anhepatic phase to prevent graft reinfection. Both
      patients are doing well with no evidence of recurrent viremia at 36 and 24 months
      of follow-up after repeat transplantation, respectively. Our results suggest that
      in those with cholestatic HCV infection, repeat transplantation after viral
      clearance is feasible and can occur without reinfection of the graft, challenging
      the current practice of denying retransplantation for patients with cholestatic
      HCV. The role of anhepatic administration of interferon deserves further
      examination, and this combination may provide a solution in a subset of patients
      with an otherwise poor prognosis.

PMID- 18044745
TI  - Which lesions cause myocardial infarctions? Lambs versus lions.

PMID- 18044744
TI  - Rab6 family proteins interact with the dynein light chain protein DYNLRB1.
AB  - The small GTPase Rab6 is a key regulator in the retrograde transfer from
      endosomes via the Golgi to the ER. Three isoforms of Rab6 have been identified,
      the ubiquitously expressed Rab6A and Rab6A', and the brain specific Rab6B. Recent
      studies have shown that Rab6A' is the major isoform regulating this retrograde
      transport. Cytoplasmic dynein is the main motor protein complex for this
      transport. Dynein consists of two heavy chains, two intermediate chains, four
      light intermediate chains and several light chains, called roadblock/LC7 proteins
      or DYNLRB proteins. In mammalian cells two light chain isoforms have been
      identified, DYNLRB1 and DYNLRB2. We here show with yeast-two-hybrid, co
      immunoprecipitation and pull down studies that DYNLRB1 specifically interacts
      with all three Rab6 isoforms and co-localises at the Golgi. This is the first
      example of a direct interaction between Rab6 isoforms and the dynein complex.
      Pull down experiments showed further preferred association of DYNLRB1 with GTP
      bound Rab6A and interestingly GDP-bound Rab6A' and Rab6B. In addition DYNLRB1 was
      found in the Golgi apparatus where it co-localises with EYFP-Rab6 isoforms.
      DYNLRB is a putative modulator of the intrinsic GTPase activity of GTP-binding
      proteins. In vitro we were not able to reproduce this effect on Rab6 GTPase
      activity.

PMID- 18044746
TI  - Presentation of an acquired urea cycle disorder post liver transplantation.
AB  - The liver's role as the largest organ of metabolism and the unique and often
      critical function of liver-specific enzyme pathways imply a greater risk to the
      recipient of acquiring a donor metabolic disease with liver transplants versus
      other solid organ transplants. With clinical consequences rarely reported, the
      frequency of solid organ transplant transfer of metabolic disease is not known.
      Ornithine transcarbamylase deficiency (OTCD), although rare, is the most common
      of the urea cycle disorders (UCDs). Because of phenotypic heterogeneity, OTCD may
      go undiagnosed into adulthood. With over 5000 liver transplant procedures
      annually in the United States, the likelihood of unknowingly transmitting OTCD
      through liver transplantation is very low. We describe the clinical course of a
      liver transplant recipient presenting with acute hyperammonemia and
      encephalopathy after receiving a liver graft form a donor with unrecognized OTCD.

PMID- 18044747
TI  - Three-dimensional and quantitative analysis of atherosclerotic plaque composition
      by automated differential echogenicity.
AB  - OBJECTIVE: To validate automated and quantitative three-dimensional analysis of
      coronary plaque composition using intracoronary ultrasound (ICUS). BACKGROUND:
      ICUS displays different tissue components based on their acoustic properties in
      256 grey-levels. We hypothesised that computer-assisted image analysis
      (differential echogenicity) would permit automated quantification of several
      tissue components in atherosclerotic plaques. METHODS AND RESULTS: Ten 40-mm-long
      left anterior descending specimens were excised during autopsy of which eight
      could be successfully imaged by ICUS. Histological sections were taken at 5 mm
      intervals and analyzed. Since most of the plaques were calcified and having a
      homogeneous appearance, one specimen with a more heterogeneous composition was
      further examined: at each interval of 5 mm, 15 additional sections (every 100
      microm) were evaluated. Plaques were scored for echogenicity against the
      adventitia: brighter (hyperechogenic) or less bright (hypoechogenic). Areas of
      hypoechogenicity correlated with the presence of smooth muscle cells. Areas of
      hyperechogenicity correlated with presence of collagen, and areas of
      hyperechogenicity with acoustic shadowing correlated with calcium. None of these
      comparisons showed statistical significant differences. CONCLUSION: This ex vivo
      feasibility study shows that automated three-dimensional differential
      echogenicity analysis of ICUS images allows identification of different tissue
      types within atherosclerotic plaques. This technology may play a role as an
      additional tool in longitudinal studies to trace possible changes in plaque
      composition.

PMID- 18044748
TI  - Coaxial double catheter technique followed by buddy wire placement for ostial
      lesion of right coronary artery with anterior take-off.
AB  - This report describes a technique for percutaneous coronary intervention in an
      ostial lesion with difficult take-off utilising an 8F guiding catheter and a 5F
      125 cm-long diagnostic catheter followed by buddy wire placement.

PMID- 18044749
TI  - Endothelial progenitor cell therapy for the treatment of coronary disease, acute
      MI, and pulmonary arterial hypertension: current perspectives.
AB  - Since their identification in 1997, bone marrow derived endothelial progenitor
      cells (EPCs) have been studied for their role in the endogenous maintenance and
      repair of endothelium and their potential regenerative capacity beyond the
      endothelium. In particular, EPCs have been tested in cell therapy approaches with
      the aim of developing novel therapies for conditions currently lacking effective
      treatment options. In this review, we discuss the scientific background and
      clinical experience using EPC delivery or mobilization for the treatment of post
      angioplasty restenosis, acute myocardial infarction and pulmonary arterial
      hypertension. Although these approaches are safe, efficacy has yet to be proven
      in large randomized clinical trials. Unfortunately, the biology of EPCs is still
      poorly understood. The success of future clinical trials depends on a better
      understanding of EPC biology and intelligent design.

PMID- 18044750
TI  - Liver retransplantation of patients with hepatitis C infection is associated with
      acceptable patient and graft survival.
AB  - Infection with hepatitis C virus (HCV) is the leading cause of liver
      transplantation (LT), while liver retransplantation (RT) for HCV is controversial
      as a result of concerns over poor outcomes. We sought to compare patient and
      graft survival after RT in patients with and without HCV. We performed a
      retrospective chart review of all patients undergoing RT at our center between
      February 1998 and April 2004. Indications for RT, HCV status, patient, and donor
      characteristics, laboratory values, and hospitalization status at RT were
      collected. A total of 108 patients (48 HCV and 60 non-HCV) underwent RT during
      the study period, with mean post-RT follow-up of 1,096 days (range, 0-2,888
      days). Grafts from donors aged>60 years were used less frequently in HCV patients
      at RT (6%) compared with LT (47%), P<0.001. There was no difference between HCV
      vs. non-HCV patients in 1- and 3-year patient survival (respectively, 79% vs.
      63%, and 71% vs. 63%) and graft survival (respectively, 67% vs. 66%, and 59% vs.
      56%). Post-RT mortality and graft failure in HCV patients occurred within the
      first year in 89% of patients, and 83% were unrelated to HCV recurrence. We
      conclude that patients should not be excluded from consideration for
      retransplantation solely on the basis of a diagnosis of HCV.

PMID- 18044751
TI  - Two-sided fluorescence resonance energy transfer for assessing molecular
      interactions of up to three distinct species in confocal microscopy.
AB  - The role of the expression patterns of proteins involved in oncogenesis can be
      understood after characterizing their multimolecular interactions. Conventional
      FRET methods permit the analysis of interaction between two molecular species at
      the most, which necessitates the introduction of new approaches for studying
      multicomponent signaling complexes. Flow cytometric as well as microscopic donor
      (dbFRET) and acceptor (abFRET) photobleaching FRET measurements were performed to
      determine the association states of ErbB2, beta1-integrin, and CD44 receptors.
      Based on consecutively applied abFRET and dbFRET methods (two-sided FRET), the
      relationship of beta1-integrin-ErbB2 heteroassociation to ErbB2 homoassociation
      and of beta1-integrin-ErbB2 heteroassociation to ErbB2-CD44 heteroassociation was
      studied by correlating pixel-by-pixel FRET values of the corresponding abFRET and
      dbFRET images in contour plots. Anticorrelation was observed between beta1
      integrin-ErbB2 heteroassociation and ErbB2 homoassociation on trastuzumab
      sensitive N87 and SK-BR-3 cells, while modest positive correlation was found
      between beta1-integrin-ErbB2 and ErbB2-CD44 heteroassociation on trastuzumab
      resistant MKN-7 cells. The FRET efficiency values of beta1-integrin-ErbB2
      heteroassociation were markedly higher at the focal adhesion regions on attached
      cells than those measured by flow cytometry on detached cells. In conclusion, we
      implemented an experimental set-up termed two-sided FRET for correlating two
      pairwise interactions of three arbitrarily chosen molecular species. On the basis
      of our results, we assume that the homoassociation state of ErbB2 is dynamically
      modulated by its interaction with beta1-integrins.

PMID- 18044752
TI  - Surgical stress and tumor behavior: impact of ischemia-reperfusion and hepatic
      resection on tumor progression.

PMID- 18044753
TI  - Morbid obesity with one or more other serious comorbidities should be a
      contraindication for liver transplantation.

PMID- 18044754
TI  - Transfusion guidelines and liver transplantation: time for consensus.

PMID- 18044755
TI  - The shorter the better?

PMID- 18044756
TI  - Patent foramen ovale - "back door" to the brain, even in kids.

PMID- 18044757
TI  - The impact of acute alcoholic hepatitis in the explanted recipient liver on
      outcome after liver transplantation.
AB  - Patients with clinical acute alcoholic hepatitis (AAH) are not considered
      suitable candidates for orthotopic liver transplantation (OLT). The histological
      correlates of AAH are often seen in the explanted liver at the time of
      transplantation. The importance of these findings remains inconclusive regarding
      their role as a prognostic marker for patient or allograft health. Our aim was to
      examine the explanted liver of patients with purely alcoholic liver disease (ALD)
      for findings of histologic AAH and to correlate these to patient and graft
      outcomes. We compared patients with and without histological AAH with patients
      transplanted for non-ALD. Of 1,097 liver transplant recipients, 148 had ALD and
      125 were non-ALD control patients with similar demographics. Thirty-two of 148
      ALD patients had histologic AAH, and 116 had bland alcoholic cirrhosis (BAC).
      Twenty-eight percent of the ALD patients reported <6 months abstinence, and 54%
      reported <12 months abstinence. There was a statistically significant
      relationship between the presence of histologic AAH and abstinence durations<12
      months (P=0.009), but not <6 months. Overall, posttransplantation patient and
      graft survival between the ALD and non-ALD groups was not significantly different
      (P=0.53). Furthermore, patient and graft survival between ALD patients with
      histologic AAH and BAC were similar (P=0.13 and P=0.11, respectively). The rate
      of posttransplantation relapse among ALD patients was 16%; however, there was no
      increase in graft loss, nor was there decreased survival compared with controls.
      The patients with histologic AAH and those with BAC had no differences in
      posttransplantation relapse (P=0.13). In multivariate analysis, patient and graft
      survival was not influenced by pretransplantation abstinence or
      posttransplantation relapse. In conclusion, histological alcoholic hepatitis in
      the explant did not predict worse outcome regarding relapse, and allograft or
      patient survival for liver transplant recipients. Caution should be exercised
      when liver histology is used to discriminate among suitable candidates for OLT
      concerning alcoholic patients.

PMID- 18044758
TI  - The CAPTURE registry: predictors of outcomes in carotid artery stenting with
      embolic protection for high surgical risk patients in the early post-approval
      setting.
AB  - BACKGROUND: The use of carotid artery stenting with embolic protection has been
      practiced for over a decade in the United States, and increasingly so since
      carotid stenting received FDA approval in 2004. While there have been attempts at
      establishing predictors of outcomes in carotid artery stenting, they have
      generally been limited to single center experiences and/or multicenter
      retrospective surveys. This report examines predictors of outcomes in carotid
      stenting in the earliest and largest prospective multicenter neurologist
      adjudicated experience in the United States post device approval. METHODS: The
      Carotid Acculink/Accunet Post-Approval Trial to Uncover Unanticipated or Rare
      Events (CAPTURE) is a prospective, multi-center registry conducted to assess
      outcomes of carotid artery stenting (CAS) in the noninvestigational setting
      following device approval for high surgical risk patients (symptomatic with > or
      =50% stenosis; asymptomatic > or =80% stenosis). A neurologist examined the
      patients before the procedure, at 24 hr and 30-days post-procedure. The primary
      endpoint was a composite of death, any stroke, or myocardial infarction within 30
      days post-procedure. Strokes and neurological events suspected to be strokes were
      adjudicated by an independent Clinical Events Adjudication Committee (CEAC) using
      prespecified definitions. Logistic regression analysis was performed to determine
      clinical, procedural, and anatomic predictors of endpoint outcomes. RESULTS:
      Three thousand five hundred patients were enrolled at 144 sites by 353 physicians
      of varying specialty backgrounds and CAS experience. The 30-day primary endpoint
      event rate of death, stroke and MI was 6.3% [95% CI: 5.5-7.1%], and the rate of
      major stroke and death 2.9% [95% CI: 2.4-3.5]. Predictors of adverse outcomes
      included age, symptomatic patients, predilation prior to embolic protection
      device placement, time from symptoms to CAS procedure, and the use of multiple
      stents. CONCLUSIONS: In general, carotid stenting is performed safely in patients
      with severe stenosis at high surgical risk, with best outcomes in younger
      asymptomatic patients. However, there are certain patient and procedural
      characteristics that are associated with poorer outcomes. In these patients, the
      risk of stenting should be considered vis-a-vis both the anticipated benefit as
      well as the alternative surgical and medical options.

PMID- 18044759
TI  - Results of the multicenter first-in-man study of a novel scoring balloon catheter
      for the treatment of infra-popliteal peripheral arterial disease.
AB  - OBJECTIVE: To evaluate the AngioSculpt (ASC), a novel scoring balloon catheter
      designed to treat complex diffuse fibro-calcific atherosclerotic lesions and
      avoid device slippage during deployment, in patients with infra-popliteal
      disease. METHODS: The ASC incorporates a flexible nitinol scoring element
      containing three or more spiral struts which encircle a minimally compliant
      balloon to create focal concentration of the dilating force. Patients scheduled
      for percutaneous intervention of infra-popliteal arteries or planned amputation
      and with a reference vessel diameter of 1.5-3.5 mm were included in the study.
      RESULTS: A total of 42 patients and 56 lesions were treated at five sites. Of
      these, 38 patients (90.5%) presented with critical limb ischemia (Rutherford
      Class > or = 4). The ASC was successfully deployed in 98.2% (55/56) of lesions
      attempted and was used as primary therapy without stenting in 89.3% (50/56).
      Lesion morphology was complex, including moderate/severe calcification in 73%,
      lesion length 33.9 +/- 42.2 mm, bifurcation in 26.8%, and ostial in 12.5%. There
      was no significant device slippage and no perforations. Post-ASC dissections
      occurred in only six (10.7%) lesions and were minor or resolved with stenting. In
      13 patients initially referred for amputation, ASC treatment resulted in limb
      salvage. CONCLUSIONS: The ASC is highly effective in a broad range of complex
      lesion morphologies, in most cases as stand-alone therapy, is associated with a
      very low complication rate and avoids device slippage during deployment.
      Additional studies are planned to assess the long term efficacy of this promising
      new technology.

PMID- 18044760
TI  - Telomere length and risk of Parkinson's disease.
AB  - We investigated whether telomere length was associated with the risk of
      Parkinson's disease (PD) in a case-control study (96 cases and 172 age-matched
      controls) nested within the Health Professionals Follow-up Study. Relative ratio
      of telomere repeat copy number to single-gene copy number in peripheral blood
      leukocytes was determined by quantitative real time PCR. Men with shorter
      telomeres had a lower PD risk (multivariate adjusted relative risk for the lowest
      vs. the highest quartile 0.33; 95% confidence interval: 0.12-0.90). Our results
      suggest that, contrary to telomere attrition observed in several aging-related
      diseases, shorter telomeres are not associated with an increased risk of PD.

PMID- 18044761
TI  - Classification and prognosis of intrahepatic biliary stricture after liver
      transplantation.
AB  - Intrahepatic biliary stricture (IHBS) after liver transplantation (LT) may
      develop in patients with hepatic artery thrombosis, chronic rejection, or ABO
      incompatibility, as well as in patients with prolonged warm ischemia in non-heart
      beating donor (NHBD) LT. However, the clinical course and methods of management
      have not been well defined for IHBSs to date. Thus, the purpose of this study was
      to provide a classification of post-LT IHBS and to investigate patient prognosis.
      Forty-four patients who developed IHBS after NHBD LT were enrolled. On the basis
      of the cholangiographic appearance, patients were classified into 4 groups:
      unilateral focal (UF, n=8), confluence (CO, n=10), bilateral multifocal (BM,
      n=21), and diffuse necrosis (DN, n=5). The UF type was defined as cases with
      stricture only in the segmental branch of the unilateral hemiliver; the CO type
      in cases with several strictures at confluence level; and the BM type in cases
      with multiple strictures bilaterally. Cases with diffuse obliteration of
      peripheral ducts or destruction of the central architectural integrity, over a
      long segment, were classified as the DN type. Five patients with the CO type
      required several interventions requiring biliary dilatation, yet all patients
      with the UF or CO type had a good prognosis. Among the patients with the BM type,
      3 patients (14.3%) died or underwent retransplantation due to biliary
      complications, and 7 (33.3%) required repeated interventions for >1 year without
      improvement. Moreover, among 5 patients classified as the DN type, 1 (20%) died
      of biliary sepsis, 2 (40%) underwent retransplantation, and the remaining 2 (40%)
      did not recover from persistent jaundice and life-threatening cholangitis despite
      multiple interventions. In conclusion, all patients classified as UF or CO had a
      good outcome with or without additional interventions. However, all patients with
      the DN type and about half the patients with the BM type did not recover from
      life-threatening complications, despite repeated aggressive interventions; early
      retransplantation was therefore the only treatment option for these patients.

PMID- 18044762
TI  - Reduced expression of MAb6B4 epitopes on chondroitin sulfate proteoglycan
      aggrecan in perineuronal nets from cerebral cortices of SAMP10 mice: a model for
      age-dependent neurodegeneration.
AB  - The accelerated senescence-prone SAMP10 mouse strain is a model for age-dependent
      neurodegeneration and is characterized by brain atrophy and deficits in learning
      and memory. Because perineuronal nets play an important role in the synaptic
      plasticity of adult brains, we examined the distributions of molecules that
      constitute perineuronal nets in SAMP10 mouse brain samples and compared them with
      those in control SAMR1 mouse samples. Proteoglycan-related monoclonal antibody
      6B4 (MAb6B4) clearly immunostained perineuronal nets in SAMR1 mice cortices, but
      the corresponding immunostaining in SAMP10 mice was very faint. MAb6B4 recognizes
      phosphacan/PTPzeta in immature brains. However, this antibody recognized several
      protein bands, including a 400-kDa core glycoprotein from chondroitin sulfate
      proteoglycan in homogenates of mature cortices from SAMR1 mice. The 400-kDa band
      was also recognized by antiaggrecan antibodies. The aggrecan core glycoprotein
      band was also detectable in samples from SAMP10 mice, but this glycoprotein was
      faintly immunostained by MAb6B4. Because MAb6B4 recognized the same set of
      protein bands that the monoclonal antibody Cat-315 recognized in mature cerebral
      cortices of SAMR1 mice, the MAb6B4 epitope appears to be closely related to that
      of Cat-315 and presumably represents a novel type of oligosaccharide that
      attaches to aggrecans. The Cat-315 epitope colocalized with aggrecan in
      perineuronal nets from SAMR1 mouse brain samples, whereas its expression was
      prominently reduced in SAMP10 mouse brain samples. The biological significance of
      the MAb6B4/Cat-315 epitope in brain function and its relationship to the
      neurodegeneration and learning disabilities observed in SAMP10 mice remain to be
      elucidated.

PMID- 18044763
TI  - An evaluation of octogenarians undergoing percutaneous coronary intervention from
      the Melbourne Interventional Group registry.
AB  - OBJECTIVES: The objective of this study was to evaluate the clinical
      characteristics and outcomes of octogenarians (> or =80 years of age) in a
      contemporary, multi-centre percutaneous coronary intervention (PCI) registry.
      BACKGROUND: Octogenarians are increasingly referred for PCI. This patient
      population frequently has significant comorbidities, which result in major
      therapeutic challenges. METHODS: The study population consisted of consecutive
      patients undergoing PCI in seven major Australian hospitals, who were treated
      over a 2-year period (2004-2005). RESULTS: Of 4,360 PCI's, 11.3% (n = 491) were
      performed in octogenarians and 88.7% (n = 3,869) in patients <80 years.
      Octogenarians (compared with patients <80 years of age) were more likely female
      and have greater comorbidities such as cerebrovascular disease, renal impairment,
      congestive heart failure, and chronic airway disease. Octogenarians more
      frequently presented with acute coronary syndromes and cardiogenic shock.
      Octogenarians had significantly increased 30-day (6.0 vs. 1.4%, P < 0.01) and 12
      month mortality (8.4% vs. 2.5%, P < 0.01), and major adverse cardiac event rates
      [(MACE), 30 days 11.3% vs. 5.4%, P < 0.01 and 12-months 18.7% vs. 12.9%, P =
      0.04]. Cardiogenic shock, ST-segment elevation myocardial infarction, chronic
      renal failure, and age > or =80 years were independent predictors of 12-month
      mortality. CONCLUSIONS: Octogenarians comprise a significant cohort of patients
      undergoing PCI. Octogenarians have more comorbidities, and higher rates of
      mortality and MACE, mandating thorough clinical evaluation before acceptance for
      PCI.

PMID- 18044764
TI  - Using livers from donation after cardiac death donors--a proposal to protect the
      true Achilles heel.

PMID- 18044765
TI  - Be careful: they are getting older and so are those around them.

PMID- 18044767
TI  - Coupling between limb tremor and postural sway in Parkinson's disease.
AB  - Increased tremor and postural instability are motor problems commonly associated
      with Parkinson's disease (PD). Despite the similarity between these oscillatory
      forms, little is known about the relation between them, especially for
      individuals with enhanced tremor. This study was designed to examine the nature
      of any relation between center of pressure (COP) excursions and postural/resting
      limb tremor of young, older individuals, and Parkinsonian participants in their
      different medication states. The resting and postural tremor for the PD
      participants was characterized by a single, prominent peak frequency between 4
      and 7 Hz. The postural tremor for young/older participants contained smaller
      peaks between 1 to 4 and 7 to 12 Hz although no prominent peak was seen in their
      resting tremor. The AP and ML COP dynamics of all participants was characterized
      by a major peak between 0.1 and 0.5 Hz. An additional peak was observed in the
      COP output of the PD participants between 4 and 7 Hz. While no tremor-COP
      coupling was observed for the young/old groups, coherence analysis revealed a
      significant degree of coupling between COP motion and tremor between 4 and 7 Hz
      for PD participants. These results highlight that the amplified tremor in PD can
      manifest itself in COP dynamics. This finding may have implications for postural
      stability for this patient group.

PMID- 18044766
TI  - Expansion of selection criteria for patients with hepatocellular carcinoma in
      living donor liver transplantation.
AB  - In the present study, the results of living donor liver transplantation (LDLT)
      for 125 hepatocellular carcinoma (HCC) patients were analyzed to determine
      optimal criteria exceeding the Milan criteria (MC) but still with predictably
      good outcomes. On the basis of pretransplant imaging studies, 70 patients met the
      MC, and 55 patients did not. Patients who exceeded the MC but presented with
      <or=10 tumors all<or=5 cm in diameter (n=30) displayed 5-year recurrence rates
      (7.3%) similar to those of patients within the MC (9.7%, P=0.8787). According to
      the results of multivariate analysis of risk factors for recurrence among
      preoperative tumor variables, we have defined the new criteria, namely <or=10
      tumors all<or=5 cm in diameter and protein induced by vitamin K absence or
      antagonist-II (PIVKA-II)<or=400 mAU/mL. The 78 patients who met the new criteria
      showed significantly lower 5-year recurrence rates (4.9%) than the 40 patients
      who exceeded them (60.5%, P<0.0001). Similarly, 5-year survival rates
      significantly differed between these groups (86.7% versus 34.4%, respectively;
      P<0.0001). In conclusion, selection criteria for patients with HCC undergoing
      LDLT may be safely extended to <or=10 tumors all<or=5 cm in diameter and PIVKA
      II<or=400 mAU/mL with acceptable outcomes.

PMID- 18044768
TI  - Benign tremulous parkinsonism: a clinicopathological study.

PMID- 18044769
TI  - Effect of prophylaxis on fungal infection and costs for high-risk liver
      transplant recipients.
AB  - We sought to determine whether the prophylactic use of amphotericin B products
      (conventional amphotericin B and liposomal amphotericin B) reduces the incidence
      of fungal infections in high-risk liver transplant recipients, and if so, whether
      this lowers the cost of care. The study sample comprised 232 adult orthotopic
      liver transplants performed from 1994 to 2005 at a single center for patients
      classified as being at high risk for fungal infections. High-risk patients who
      received transplants with a prophylaxis regimen of amphotericin B (n=58
      transplants) were compared with high-risk patients who received no prophylaxis
      (n=174 transplants). Fungal infections occurred in 3 transplants (5.17%) of those
      who received amphotericin B and 28 transplants (16.09%) in those without
      prophylaxis (P=0.0432). Regression models were used to analyze fungal infection
      and costs for the 232 high-risk transplants. Failure to offer prophylaxis
      conferred a 4-fold greater risk of fungal infection (P=0.046) compared with those
      who received amphotericin B. A fungal infection in a high-risk recipient
      increased mean costs by 46.48%. The indirect effect of prophylaxis (operating
      through infection reduction) is estimated to reduce overall costs in high-risk
      patients by 8.73%.

PMID- 18044770
TI  - Fregoli syndrome associated with levodopa treatment.

PMID- 18044771
TI  - Venous outflow obstruction in liver transplantation is associated with the
      anastomotic technique.

PMID- 18044772
TI  - Comparison of the efficacy and safety of miconazole 50-mg mucoadhesive buccal
      tablets with miconazole 500-mg gel in the treatment of oropharyngeal candidiasis:
      a prospective, randomized, single-blind, multicenter, comparative, phase III
      trial in patients treated with radiotherapy for head and neck cancer.
AB  - BACKGROUND: Topical antifungal treatments are recommended but rarely used as
      first-line therapy for oropharyngeal candidiasis (OPC) in patients with cancer.
      Miconazole Lauriad 50-mg mucoadhesive buccal tablet (MBT) Loramyc reportedly
      delivered rapid and prolonged, effective concentrations of miconazole in the
      mouth. The objective of the current study was to compare MBT with miconazole 500
      mg oral gel (MOG) in patients with head and neck cancer. METHODS: Two hundred
      eighty-two patients with head and neck cancer received a 14-day treatment of
      either single-dose MBT or MOG administered in 4 divided doses. The primary
      endpoint was clinical success at Day 14, and secondary endpoints included
      clinical success at Day 7, clinical cure, improvement in clinical symptoms,
      mycologic cure, recurrence rate, and safety. RESULTS: The success rate was
      statistically not inferior (P < .0001) in the MBT population to the rate observed
      in the MOG group (56% vs 49%, respectively; P < .0001). After adjustment for the
      extent of lesions and salivary secretions, a trend toward superiority was
      observed in favor of MBT (P = .13), particularly among patients with multiple
      lesions (P = .013). Results for secondary endpoints were comparable to those
      observed for the primary endpoint. Compliance with MBT was excellent, and >80% of
      patients completed treatment. Both treatments were safe. CONCLUSIONS: The success
      rate of MBT Loramyc was significantly not inferior to that of MOG in the
      treatment of cancer patients with OPC; and, after adjusting for prognostic
      variables, it was more effective than MOG. MBT was well tolerated and, thus, may
      be recommended as first-line treatment in cancer patients who have OPC as an
      alternative to systemic antifungal agents. Society.

PMID- 18044773
TI  - Tibial intervention; no fear!

PMID- 18044774
TI  - Thoracic aneurysm repair: managing severe tortuosity with brachiofemoral
      traction.
AB  - Challenging anatomy of the thoracic aorta is often encountered, and aortic
      tortuosity may be a major impediment to the propulsion of the stent-graft.
      Traction on both ends of a guidewire, with one end exiting the right upper
      extremity and the other end exiting the lower extremity, is an excellent option
      to manage thoracic aorta tortuosity. Careful application of simple guidelines may
      lessen associated risks and improve safety.

PMID- 18044775
TI  - Catheter-directed thrombolysis of acute lower extremity arterial thrombosis in a
      patient with heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is an underdiagnosed problem, and the
      optimal treatment of arterial thrombosis in patients with HIT remains
      controversial. There are many angiographic procedures which require heparin as an
      adjunctive agent; however, some of the heparin-related complications and their
      management remains unclear. We are presenting a 77-year-old male patient with
      HIT, who developed acute lower extremity limb threatening ischemia due to
      arterial thrombosis. In our case, the patient has been successfully treated with
      percutaneous catheter-directed thrombolysis with tissue plasminogen activator and
      a direct thrombin inhibitor argatroban.

PMID- 18044777
TI  - Analysis of bifurcation lesions treated with novel drug-eluting dedicated
      bifurcation stent system: intravascular ultrasound results of the AXXESS PLUS
      trial.
AB  - OBJECTIVE: The aim of this intravascular ultrasound (IVUS) study was to assess
      the efficacy of the AXXESS Plus stent system for the treatment of bifurcation
      coronary lesions. BACKGROUND: The AXXESS Plus is a novel bifurcation drug-eluting
      stent, comprised of a self-expanding flare-shaped stent platform and
      bioabsorbable polymer coating that releases Biolimus A9. METHODS: Data were
      obtained from the AXXESS PLUS trial, a prospective, multicenter, nonrandomized,
      single-arm study to evaluate safety and efficacy. Six-month follow-up IVUS
      analysis was available in 49 cases. Volumetric analysis using Simpson's method
      within the AXXESS stent, and cross-sectional analysis at the ostium of main
      branch and/or side branch was performed. Impact of bifurcation angle on stent
      expansion at the carina was also evaluated. RESULTS: Within the AXXESS stent,
      neointimal volume obstruction percentage was 2.3% +/- 2.2%, with a minimum lumen
      area of 7.9 +/- 2.6 mm(2). Lumen area was 5.2 +/- 1.7 mm(2) at main branch
      ostium, and 4.0 +/- 1.5 mm(2) at side branch ostium. In two cases, incomplete
      stent apposition was observed at the proximal edge of the AXXESS stent. In one
      case, a gap between the AXXESS stent and an additional stent was observed.
      Greater bifurcation angle inversely correlated with smaller stent area at side
      branch ostium (r = -0.54, P = 0.03) but not at main branch ostium (r = -0.2, P =
      0.29). CONCLUSIONS: This novel self-expanding, drug-eluting bifurcation stent
      demonstrated effective lesion coverage along with significant neointimal
      suppression equivalent to current generation balloon-expandable drug-eluting
      stent technology.

PMID- 18044778
TI  - Biliary complications and outcomes of liver transplantation from donors after
      cardiac death.
AB  - Biliary complications after liver transplantation (LT) using organs retrieved
      from donors after cardiac death are not well characterized. The aim of this study
      was to evaluate the severity of biliary complications and outcomes after donation
      after cardiac death liver transplantation (DCD-LT). A retrospective evaluation of
      20 DCD-LTs from 1997-2006 was performed. The recipient age was 53+/-8.7, and the
      donor age was 35+/-11 years. The warm ischemia time, cold ischemia time, peak
      alanine aminotransferase level, and peak aspartate aminotransferase level were
      33+/-12 minutes, 8.7+/-2.7 hours, 1757+/-1477 U/L, and 4020+/-3693 U/L,
      respectively. The bilirubin and alkaline phosphatase levels at hospital discharge
      after LT were 3.2+/-5.4 mg/dL and 248+/-200 U/L, respectively. During a median
      follow-up of 7.5 months (range: 1-73), 5 patients (25%; 1 death after re-LT) died
      (3 from sepsis, 1 from recurrent hepatocellular carcinoma at 4 months, and 1 from
      a cardiac event at 46 months), and additionally, 4 patients (20%) required re-LT
      (1 because of hepatic artery thrombosis, 1 because of primary graft nonfunction,
      and 2 because of biliary strictures). Twelve (60%) developed biliary
      complications, and of these, 11 (55%) had serious biliary complications. The
      biliary complications were as follows: a major bile leak for 2 patients (10%;
      both eventually underwent retransplantation), anastomotic strictures for 5
      patients (25%), hilar strictures for 7 patients (35%), extrahepatic donor duct
      strictures for 9 patients (45%), intrahepatic strictures for 10 patients (50%),
      stones for 1 patients (5%), casts for 7 patients (35%), and debris for 2 patients
      (10%). More than 1 biliary complication was seen in most patients, and these were
      unpredictable and required multiple diagnostic or therapeutic procedures. Serious
      biliary complications are common after DCD-LT, and research should focus on
      identifying donor and recipient factors that predict and prevent serious biliary
      complications.

PMID- 18044779
TI  - Modified outflow reconstruction with a venous patch in domino liver
      transplantation.

PMID- 18044780
TI  - Liver and partial atrium transplantation for chronic Budd-Chiari syndrome.

PMID- 18044781
TI  - Reply: geographic disparities and deceased donor liver transplantation within a
      single UNOS region.

PMID- 18044782
TI  - Time to review the selection criteria for transplantation in paracetamol-induced
      fulminant hepatic failure?

PMID- 18044783
TI  - Alloimmunization to red blood cell antigens affects clinical outcomes in liver
      transplant patients.
AB  - Transfusion therapy of liver transplant patients remains a challenge. High
      volumes of intraoperative blood transfusion have been shown to increase the risk
      of poor graft or patient survival. We conducted a retrospective study of 209
      consecutive liver transplant cases at our institution. Only patients receiving
      their first liver transplant, with no other simultaneous organ transplants, were
      included. Cox proportional hazard modeling was used to identify clinical
      variables correlated with postoperative patient mortality. Statistically
      significant variables for poor patient survival were the number of red blood cell
      and plasma units transfused, a history of red blood cell alloantibodies, and the
      immunosuppressive regimen used. History of pregnancy also approached statistical
      significance but was less robust than the other 3 variables. Our findings suggest
      that blood transfusion and immune modulation greatly affect the survival of
      patients after liver transplantation.

PMID- 18044785
TI  - Warning regarding gadolinium and nephrogenic systemic fibrosis.

PMID- 18044784
TI  - Resolution of hepatopulmonary syndrome after auxiliary partial orthotopic liver
      transplantation in Abernethy malformation. A case report.
AB  - Congenital absence of portal vein and extrahepatic portocaval shunt, also
      referred to as an Abernethy type 1, is a rare malformation of the mesenteric
      vasculature. A 9-year-old girl presented with dyspnea on exertion and
      orthodeoxia. A diagnosis of an Abernethy malformation type 1b and hepatopulmonary
      syndrome (HPS) was made, and she underwent auxiliary partial orthotopic liver
      transplantation (APOLT). Symptoms and signs of HPS resolved 2 months after the
      operation. HPS in Abernethy syndrome is a manifestation of normal portal blood
      flow bypassing the liver and can be ameliorated by redirecting blood flow to a
      segment of liver with normal portal anatomy. APOLT is a feasible and successful
      surgical procedure for patients with Abernethy malformation and HPS.

PMID- 18044786
TI  - Ischemia-reperfusion of small liver remnant promotes liver tumor growth and
      metastases--activation of cell invasion and migration pathways.
AB  - Elucidating the mechanism of liver tumor growth and metastasis after hepatic
      ischemia-reperfusion (I/R) injury of a small liver remnant will lay the
      foundation for the development of therapeutic strategies to target small liver
      remnant injury, and will reduce the likelihood of tumor recurrence after major
      hepatectomy or liver transplantation for liver cancer patients. In the current
      study, we aimed to investigate the effect of hepatic I/R injury of a small liver
      remnant on liver tumor development and metastases, and to explore the precise
      molecular mechanisms. A rat liver tumor model that underwent partial hepatic I/R
      injury with or without major hepatectomy was investigated. Liver tumor growth and
      metastases were compared among the groups with different surgical stress. An
      orthotopic liver tumor nude mice model was used to further confirm the
      invasiveness of the tumor cells from the above rat liver tumor model. Significant
      tumor growth and intrahepatic metastasis (5 of 6 vs. 0 of 6, P=0.015), and lung
      metastasis (5 of 6 vs. 0 of 6, P=0.015) were found in rats undergoing I/R and
      major hepatectomy compared with the control group, and was accompanied by
      upregulation of mRNA levels for Cdc42, ROCK (Rho kinase), and vascular
      endothelial growth factor, as well as activation of hepatic stellate cells. Most
      of the nude mice implanted with liver tumor from rats under I/R injury and major
      hepatectomy developed intrahepatic and lung metastases. In conclusion, hepatic
      I/R injury of a small liver remnant exacerbated liver tumor growth and metastasis
      by marked activation of cell adhesion, invasion, and angiogenesis pathways.

PMID- 18044787
TI  - Effect of body mass index on the survival benefit of liver transplantation.
AB  - Obese patients are at higher risk for morbidity and mortality after liver
      transplantation (LT) than nonobese recipients. However, there are no reports
      assessing the survival benefit of LT according to recipient body mass index
      (BMI). A retrospective cohort of liver transplant candidates who were initially
      wait-listed between September 2001 and December 2004 was identified in the
      Scientific Registry of Transplant Recipients database. Adjusted Cox regression
      models were fitted to assess the association between BMI and liver transplant
      survival benefit (posttransplantation vs. waiting list mortality). During the
      study period, 25,647 patients were placed on the waiting list. Of these, 4,488
      (17%) underwent LT by December 31, 2004. At wait-listing and transplantation,
      similar proportions were morbidly obese (BMI>or=40; 3.8% vs. 3.4%, respectively)
      and underweight (BMI<20; 4.5% vs. 4.0%, respectively). Underweight patients
      experienced a significantly higher covariate-adjusted risk of death on the
      waiting list (hazard ratio [HR]=1.61; P<0.0001) compared to normal weight
      candidates (BMI 20 to <25), but underweight recipients had a similar risk of
      posttransplantation death (HR=1.28; P=0.15) compared to recipients of normal
      weight. In conclusion, compared to patients on the waiting list with a similar
      BMI, all subgroups of liver transplant recipients demonstrated a significant
      (P<0.0001) survival benefit, including morbidly obese and underweight recipients.
      Our results suggest that high or low recipient BMI should not be a
      contraindication for LT.

PMID- 18044788
TI  - Validation of limited sampling strategy for the estimation of mycophenolic acid
      exposure in Chinese adult liver transplant recipients.
AB  - Mycophenolate mofetil (MMF) is indicated as immunosuppressive therapy in liver
      transplantation. The abbreviated models for the estimation of mycophenolic acid
      (MPA) area under the concentration-time curve (AUC) have been established by
      limited sampling strategies (LSSs) in adult liver transplant recipients. In the
      current study, the performance of the abbreviated models to predict MPA exposure
      was validated in an independent group of patients. A total of 30 MPA
      pharmacokinetic profiles from 30 liver transplant recipients receiving MMF in
      combination with tacrolimus were used to compare 8 models' performance with a
      full 10 time-point MPA-AUC. Linear regression analysis and Bland-Altman analysis
      were used to compare the estimated MPA-AUC0-12h from each model against the
      measured MPA-AUC0-12h. A wide range of agreement was shown when estimated MPA
      AUC0-12h was compared with measured MPA-AUC0-12h, and the range of coefficient of
      determination (r2) was from 0.479 to 0.936. The model based on MPA
      pharmacokinetic parameters C1h, C2h, C6h, and C8h had the best ability to predict
      measured MPA-AUC0-12h, with the best coefficient of determination (r2=0.936), the
      excellent prediction bias (2.18%), the best prediction precision (5.11%), and the
      best prediction variation (2SD=+/-7.88 mg.h/L). However, the model based on MPA
      pharmacokinetic sampling time points C1h, C2h, and C4h was more suitable when
      concerned with clinical convenience, which had shorter sampling interval, an
      excellent coefficient of determination (r2=0.795), an excellent prediction bias
      (3.48%), an acceptable prediction precision (14.37%), and a good prediction
      variation (2SD=+/-13.23 mg.h/L). Measured MPA-AUC0-12h could be best predicted by
      using MPA pharmacokinetic parameters C1h, C2h, C6h, and C8h. The model based on
      MPA pharmacokinetic parameters C1h, C2h, and C4h was more feasible in clinical
      application.

PMID- 18044789
TI  - Long term safety: not only a drug eluting stents issue.

PMID- 18044791
TI  - Clinical and angiographic results of percutaneous coronary revascularization
      using a trilayer stainless steel-tantalum-stainless steel phosphorylcholine
      coated stent: the TriMaxx trial.
AB  - BACKGROUND: The TriMaxx coronary stent system includes a novel trilayer metal
      stent having two outer layers of 316L stainless steel and with an inner 0.0007
      inches layer of tantalum. This enables creation of a maximally flexible and thin
      device (0.0029 inches) while still maintaining the requisite strength and
      radiopacity for effective implantation. OBJECTIVES: The objective of this multi
      center, single-arm prospective clinical trial was to assess the safety and
      performance of the TriMaxx stent for the treatment of single de novo coronary
      artery lesions. METHODS: One hundred patients with ischemic coronary occlusive
      disease because of single de novo obstructive lesions of native coronary arteries
      were treated with 3 x 15 or 3 x 18 mm TriMaxx stents in four hospitals in Brazil
      and Germany between May of 2004 and September of 2005. An independent core
      laboratory analyzed the quantitative coronary angiography (QCA) results
      immediately after stent implantation, and after six months. RESULTS: The lesion,
      procedure, and device-deployment success rates were 100, 99, and 100%,
      respectively. Eighty-eight patients underwent follow-up angiography at 6 +/- 1
      months. After six months, 13 (13%) of patients had sustained major adverse
      cardiac events, including 9.0% that required target lesion revascularization
      (TLR). The follow-up angiographic studies revealed a binary in-stent restenosis
      rate of 25% with in-stent late lumen loss of 0.94 +/- 0.57 mm. CONCLUSIONS: These
      results demonstrate that the TriMaxx stent can be safely deployed for the
      treatment of single de novo coronary occlusive lesions with six-month clinical
      and angiographic results rates comparable to historical results using other bare
      metal stents.

PMID- 18044792
TI  - Transgene expression of human PON1 Q in mice protected the liver against CCl4
      induced injury.
AB  - BACKGROUND: Oxidative stress, often in association with decreased antioxidant
      defenses, plays a pathogenetic role in both initiation and progression of liver
      injuries, leading to almost all clinical and experimental conditions of chronic
      liver diseases. Human paraoxonase 1 (hPON1) is a liver-synthesized enzyme
      possessing antioxidant properties. Here, we investigate the effects of transgene
      expressed hPON1 Q on alleviating lipid peroxidation and preventing liver injury
      in a mouse model. METHODS: The hPON1 Q gene was cloned into pcDNA3.0 plasmid and
      electro-transferred into mouse skeletal muscle. After CCl4 had been administrated
      to induce liver injury, mice were monitored for serum levels of alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and malonyldialdehyde
      (MDA). The extent of CCl4-induced liver injury was also analyzed through
      histopathological observations. RESULTS: After gene delivery, hPON1 mRNA
      expression was detected in mouse muscle and serum PON1 activity was 1.5 times
      higher than that of the control counterpart. In the PON1 Q gene transferred mice,
      protection against CCl4-induced liver injury was reflected by significantly
      decreased serum ALT, AST and MDA levels compared to those in control mice (P <
      0.01). Histological observations also revealed that hepatocyte necrosis,
      hemorrhage, vacuolar change and hydropic degeneration were apparent in control
      mice after CCl4 administration. In contrast, the damage was significantly
      prevented (P < 0.01) in the hPON1 Q transferred mice. CONCLUSIONS: Intramuscular
      electro-transfer of the hPON1 Q gene led to efficient expression of hPON1 in
      mice. Elevated levels of PON1, by virtue of its potency to alleviate oxidative
      stress, could protect mice from suffering CCl4-induced liver damage.

PMID- 18044793
TI  - AAV serotype 1 mediates more efficient gene transfer to pig myocardium than AAV
      serotype 2 and plasmid.
AB  - Adeno-associated virus (AAV) has many properties of an ideal vector for delivery
      of therapeutic genes into the myocardium. Previous studies in a mouse model of
      myocardial infarction showed that AAV serotype 1 (AAV1) is superior to AAV
      serotypes 2-5 to transfer genes into the myocardium by direct injection. Since
      vectors may behave differently in humans and because the human and the pig hearts
      resemble each other closely, we tested whether AAV1 is also superior to AAV2 in
      transferring genes into the pig myocardium. We also compared gene transduction
      efficiency between AAV vectors and plasmid. We injected CMVLacZ and CMVVEGF
      (vectors with the cytomegalovirus (CMV) promoter driving LacZ and VEGF gene
      expression) unpackaged or packaged in AAV serotypes 1 or 2 capsids into pig
      myocardium. Hearts were collected 3, 14 and 28 days after the injection. Gene
      expression was analyzed by real-time reverse-transcription polymerase chain
      reaction (RT-PCR) and histological staining. Capillaries and smooth muscle alpha
      actin (SMA)-positive vessels were quantified. Potential lymphocyte infiltration
      at the injection sites was analyzed by immunostaining using specific antibodies.
      As in the mouse, AAV1 mediated better gene transduction than AAV2. Plasmid
      mediated minimal gene expression only. More capillaries and SMA-positive vessels
      were detected at AAV1CMVVEGF- and AAV2CMVVEGF-injected than AAV1CMVLacZ-injected
      sites. We did not detect inflammatory cell infiltration at the injection sites.
      In conclusion, by direct injection, AAV1 is more efficient than AAV2, and plasmid
      is inefficient in mediating gene transfer into the pig myocardium. AAV-mediated
      VEGF gene transfer can also induce neovascular formation in the pig myocardium.

PMID- 18044794
TI  - Impact of late-life self-reported emotional problems on Disability-Free Life
      Expectancy: results from the MRC Cognitive Function and Ageing Study.
AB  - OBJECTIVES: Depression in old age is a major public health problem though its
      relationship to onset of disability and death is not well understood. We aim to
      quantify the impact of late-life self-reported depression and emotional problems
      on both the length and quality of remaining life. METHODS: Longitudinal analysis
      of 11,022 individuals from the MRC Cognitive Function and Ageing Study (MRC
      CFAS), multi-centre longitudinal study on ageing in individuals age 65 years and
      older living in England and Wales. Individuals have been followed at intermittent
      time intervals over 10 years. Subjects reporting at baseline that they had
      consulted about emotional problems for the first time since the age of 60 years
      were considered, along with a subgroup where a GP suggested depression.
      Disability was defined as an IADL or ADL disability that required help at least
      once a week. Total and Disability-Free Life Expectancy (TLE and DFLE) were
      calculated using multi-state models, separately by gender, and with presence of
      emotional problems/depression and multimorbidity as covariates. RESULTS:
      Emotional problems had a greater impact on DFLE than TLE, reducing DFLE by 1.8
      years, but TLE by only 0.5 years at age 65 with the effect increasing with age.
      The effect was most marked in older people reporting other co-morbidities where
      emotional problems in addition resulted in a reduction of 0.9 years in total and
      2.6 years disability-free. CONCLUSIONS: Although emotional problems were only
      self-reported, these results highlight the burden of late-life depression on the
      quality of remaining years of life.

PMID- 18044795
TI  - Low molecular weight hyaluronan shielding of DNA/PEI polyplexes facilitates CD44
      receptor mediated uptake in human corneal epithelial cells.
AB  - AIM: It was the aim of this study to prepare purified DNA/PEI polyplexes, which
      are coated with hyaluronan to facilitate CD44 receptor mediated uptake of the
      DNA/PEI polyplex and to reduce unspecific interactions of the complex with
      negatively charged extracellular matrix components on the ocular surface.
      METHODS: Hyaluronans of different molecular weights (<10 kDa, 10-30 kDa and 30-50
      kDa) were isolated after enzymatic degradation of high molecular weight
      hyaluronan via ultrafiltration by centrifugation. The influence of the different
      hyaluronans used for coating on the stability and transfection efficiency of the
      complexes was evaluated in vitro. Transfection and uptake studies were performed
      in human corneal epithelial (HCE) cells. CD44 receptor expression of this cell
      model was evaluated by immunohistochemistry. RESULTS: Coating of purified DNA/PEI
      polyplexes with low molecular weight hyaluronan (<10 kDa) facilitated receptor
      mediated uptake via the CD44 receptor in HCE cells, increased complex stability
      in vitro, and effectively shielded the positive surface charges of the polyplex
      without decreasing its transfection efficiency. Higher molecular weights and
      larger amounts of hyaluronan in the complexes resulted in lesser improvements in
      the stability and transfection efficacy of the complexes. CONCLUSIONS: Coating of
      polyplexes with low molecular weight hyaluronan is a promising strategy for gene
      delivery to the ocular surface, where CD44 receptor mediated uptake decreased
      cytotoxicity and reduced non-specific interactions with the negatively charged
      extracellular matrix components are considered beneficial for increased
      transfection efficiency of non-viral vectors.

PMID- 18044796
TI  - Developing multidisciplinary guidelines for the management of early rheumatoid
      arthritis.
AB  - OBJECTIVE: To develop an evidence based guideline, for the multidisciplinary
      management of early rheumatoid arthritis (RA). METHODS: Recommendations were
      developed using both an evidence-based approach and expert opinion. The
      scientific committee, composed of key members of the rheumatology
      multidisciplinary team used a Delphi approach to evaluate topics and standard
      statements, which formed the basis for developing recommendations for management
      of RA in the first 2 years of disease. Evidence taken from literature was used to
      support these recommendations. RESULTS: 24 evidence based recommendations for the
      management of early RA, with a grade of recommendation from A to C, were
      developed. In addition an algorithm of care was designed to promote a clear
      multidisciplinary management pathway. A mechanism for audit was also identified.
      CONCLUSION: Involvement of the multidisciplinary rheumatology team has enabled a
      holistic guideline to be developed for the management of patients presenting with
      early RA. This guideline is based around best practice that is supported by
      published literature. Whilst most statements in the guideline are based on strong
      evidence, others have been formulated by expert consensus in the absence of data
      and should serve as an opportunity to improve current practice through future
      research and audit. The development and implementation of such a guideline should
      improve the care of patients with early RA.

PMID- 18044798
TI  - Three-dimensional sonographic assessment of fetal urine production before and
      after laser surgery in twin-to-twin transfusion syndrome.
AB  - OBJECTIVE: Fetal urine production in twin-to-twin transfusion syndrome (TTTS)
      reflects the hemodynamic imbalance between the donor and recipient twins but it
      has not been measured in this particular condition. The aim of this study was to
      measure fetal urine production using three-dimensional (3D) ultrasound in donor
      and recipient twins before and after laser treatment for TTTS and to correlate
      this with umbilical venous volume flow (UVVF). METHODS: Urine production rate
      (UPR) was measured using 3D ultrasound with Virtual Organ Computer-aided AnaLysis
      (VOCAL) in 106 cases of severe TTTS. The rotation angle was set at 30 degrees .
      The bladder volume was measured twice in each fetus (V(1) and V(2)), with an
      interval of 5-30 min between measurements, in order to calculate the UPR. When
      V(2) > V(1), UPR was calculated using the formula: V(2) - V(1) /time interval.
      Together with UPR, UVVF was measured before and after treatment. Both parameters
      were corrected for fetal weight. Inter- and intraobserver variability were
      calculated in 16 cases using the intraclass correlation coefficient. RESULTS:
      Before laser treatment, UPR was significantly higher in recipients compared with
      donors (median, 14.8 and 0 mL/h/kg, mean 23.8 and 2.3 mL/h/kg, respectively, P <
      0.001), and UPR was positively correlated with UVVF in both twins. Following
      laser treatment (48 h later), UPR decreased to 9 mL/h/kg (P < 0.001) in
      recipients, while there was no change in donors. UVVF increased significantly
      from a median value of 92 to 132 mL/min/kg (P < 0.01) in donors and decreased
      significantly from 150 to 99 mL/min/kg (P < 0.001) in recipients. CONCLUSIONS: In
      TTTS UPR is correlated to UVVF and reflects the hemodynamic imbalance between
      donor and recipient twins. Following laser treatment, UPR decreases in recipients
      but is unaffected in donors. However, changes in UVVF occur in both twins. This
      suggests that although fetal renal function is driven by fetal hemodynamics,
      there may be a lag in the recovery of renal function in the donor twin.

PMID- 18044799
TI  - Chemometric analysis of disubstituent effects on the 13C chemical shifts of the
      carboxyl carbons (deltaCO) of benzoic acids. A comparative study of the
      substituent effects on the strength of benzoic acids in apolar aprotic media.
AB  - The results of measurements of substituent induced chemical shifts of carboxyl
      carbons (deltaCO) of dichloro- and difluorobenzoic acids, including the
      monosubstituted ones with substituents at meta- and/or ortho- positions, in
      chloroform-d and strengths of these acids (log K) in chlorobenzene show an
      anomalous reverse trend between deltaCO and log K, while the electron density at
      carboxyl carbons should influence similarly both deltaCO and log K. A detailed
      chemometric analysis of comparison of disubstituent effects between deltaCO and
      log K on the basis of Fujita-Nishioka's multiparameter approach and assumption of
      additivity of substituent effects shows a dominance of the localized pi
      polarization mechanism relative to simple electrostatic effects upon deltaCO.
      Further, steric factors play a significant role in determining deltaCO whereas
      with respect to log K they were insignificant. The overall anomaly has been
      rationalized keeping in mind that, while log K is a gross measure of energy
      differences between the ionized and unionized forms of the acids, deltaCO is a
      very sensitive probe for determining changes in electron density at the carboxyl
      carbon of the unionized acid.

PMID- 18044797
TI  - Mood, cognition and in vivo protein imaging: the emerging nexus in clinical
      neuroscience.
AB  - INTRODUCTION: Disorders of mood and cognition overlap in the elderly and there is
      an emerging consensus that both groups of disorders share neurobiological
      substrates. METHODS: Salient peer reviewed articles focusing on late-life
      depression, structural neuroimaging and recent developments in positron emission
      tomography based in vivo protein imaging. RESULTS: Epidemiological and clinical
      evidence indicates that mood and cognition in the elderly are clinically inter
      related and common neurobiological mechanisms may underlie both groups of
      disorders. Degenerative, vascular and related mechanisms like genetically
      programmed abnormal protein deposition may provide the underlying neurobiological
      links between these disorders. CONCLUSIONS: Modern neuroimaging approaches such
      as positron emission tomography (PET) based in vivo protein binding may help
      further elucidate common pathophysiological mechanisms and assist in the early
      identification of patients at risk for developing dementia over time. These
      developments have important mechanistic and public health significance in the
      elderly.

PMID- 18044800
TI  - Disorder in condensed matter systems: proton spin lattice relaxation study of the
      mixed systems of betaine phosphate and glycine phosphite, BPxGPI(1-x).
AB  - Proton NMR relaxation measurements have been carried out in the mixed system of
      antiferroelectric (AFE) betaine phosphate (BP) and ferroelectric (FE) glycine
      phosphite (GPI), BPxGPI(1-x), at 11.4 and 23.3 MHz from 300 to 100 K for x=0.3,
      0.4, 0.5, 0.6, 0.7 and 0.8. The temperature dependence of spin lattice relaxation
      (SLR) time follows the BPP model in the parent compounds, while the Larmor
      frequency dependence of T1 in the mixed system is rather unusual. The T1 curve
      exhibits different slopes for the low-temperature wings at the two frequencies,
      which is a clear experimental evidence of the presence of different methyl groups
      with different activation energies (Ea), indicating disorder. For x=0.3 and 0.4,
      biexponential recovery of magnetization has been observed below 190 K, showing
      that the degree of disorder varies with the concentration. The temperature
      dependence of relaxation time data has been interpreted in terms of NH3,
      trimethyl ammonium and methyl group reorientations.

PMID- 18044801
TI  - 17O NMR investigation of phosphite hydrolysis mechanisms.
AB  - The use of solution 17O NMR spectroscopy in verifying the mechanism of trialkyl
      phosphite hydrolysis is presented. Trimethyl phosphite was reacted with 17O
      labeled H2O at different temperatures and two reactant concentrations, with the
      reaction being monitored by 17O NMR. Kinetic details elucidated from the NMR
      spectra are also discussed.

PMID- 18044802
TI  - Co-acquisition of hyperpolarised 13C and 15N NMR spectra.
AB  - Recent developments in dynamic nuclear polarisation now allow significant
      enhancements to be generated in the cryo solid state and transferred to the
      liquid state for detection at high resolution. We demonstrate that the Ardenkjaer
      Larsen method can be extended by taking advantage of the properties of the trityl
      radicals used. It is possible to hyperpolarise 13C and 15N simultaneously in the
      solid state, and to maintain these hyperpolarisations through rapid dissolution
      into the liquid state. We demonstrate the almost simultaneous measurement of
      hyperpolarised 13C and hyperpolarised 15N NMR spectra. The prospects for further
      improvement of the method using contemporary technology are also discussed.

PMID- 18044803
TI  - ESR/DFT study of bis-iminophosphorane cation radicals.
AB  - Bis-iminophosphoranes containing various types of linkers between two R3P==N
      moieties were electrochemically oxidized at controlled potential in situ in the
      electron spin resonance (ESR) cavity. For linkers constituted of phenylenes,
      conjugated phenylenes or merely a dicyanoethylenic bond, this oxidation led to
      well-resolved ESR spectra which were characterized by their g values and by their
      1H, 14N and 31P isotropic hyperfine constants. These coupling constants agree
      with those calculated by DFT for the corresponding cation radicals. Experimental
      and theoretical results clearly indicate that in these species the unpaired
      electron is mostly delocalized on the bridge and on the nitrogen atoms while the
      spin density on the phosphorus atoms is particularly small. Cyclic voltammetry
      and ESR spectra show that the nature of the bridge between the two
      iminophosphoranes considerably influences the oxidation potential of the compound
      as well as the stability of the radical cation. Information about the
      conformation of the precursor containing two Ph3P==N moieties separated by a -
      C(CN)==C(CN)--group was obtained from its crystal structure.

PMID- 18044804
TI  - Experimental and quantum-chemical studies of 1H, 13C and 15N NMR coordination
      shifts in Pd(II) and Pt(II) chloride complexes with methyl and phenyl derivatives
      of 2,2'-bipyridine and 1,10-phenanthroline.
AB  - 1H, 13C and 15N NMR studies of platinide(II) (M=Pd, Pt) chloride complexes with
      methyl and phenyl derivatives of 2,2'-bipyridine and 1,10-phenanthroline [LL=4,4'
      dimethyl-2,2'-bipyridine (dmbpy); 4,4'-diphenyl-2,2'-bipyridine (dpbpy); 4,7
      dimethyl-1,10-phenanthroline (dmphen); 4,7-diphenyl-1,10-phenanthroline (dpphen)]
      having a general [M(LL)Cl2] formula were performed and the respective chemical
      shifts (delta1H, delta13C, delta15N) reported. 1H high-frequency coordination
      shifts (Delta1Hcoord=delta1Hcomplex-delta1Hligand) were discussed in relation to
      the changes of diamagnetic contribution in the relevant 1H shielding constants.
      The comparison to literature data for similar [M(LL)(XX)], [M(LL)X2] and
      [M(LL)XY] coordination or organometallic compounds containing various auxiliary
      ligands revealed a large dependence of delta1H parameters on inductive and
      anisotropic effects. 15N low-frequency coordination shifts (Delta15Ncoord=delta
      15Ncomplex-delta15Nligand) of ca 88-96 ppm for M=Pd and ca 103-111 ppm for M=Pt
      were attributed to both the decrease of the absolute value of paramagnetic
      contribution and the increase of the diamagnetic term in the expression for 15N
      shielding constants. The absolute magnitude of Delta15Ncoord parameter increased
      by ca 15 ppm upon Pd(II)-->Pt(II) transition and by ca 6-7 ppm following dmbpy-
      >dmphen or dpbpy-->dpphen ligand replacement; variations between analogous
      complexes containing methyl and phenyl ligands (dmbpy vs dpbpy; dmphen vs dpphen)
      did not exceed+/-1.5 ppm. Experimental 1H, 13C, 15N NMR chemical shifts were
      compared to those quantum-chemically calculated by B3LYP/LanL2DZ+6
      31G**//B3LYP/LanL2DZ+6-31G*, both in vacuo and in DMSO or DMF solution.

PMID- 18044805
TI  - Experimental and quantum-chemical studies of 1H, 13C and 15N NMR coordination
      shifts in Pd(II) and Pt(II) chloride complexes with quinoline, isoquinoline, and
      2,2'-biquinoline.
AB  - 1H, 13C, and 15N NMR studies of platinide(II) (M=Pd, Pt) chloride complexes with
      quinolines (L=quinoline-quin, or isoquinoline-isoquin; LL=2,2'-biquinoline
      bquin), having the general formulae trans-/cis-[ML2Cl2] and [M(LL)Cl2], were
      performed and the respective chemical shifts (delta1H, delta13C, delta15N)
      reported. 1H coordination shifts of various signs and magnitudes
      (Delta1Hcoord=delta1Hcomplex-delta1Hligand) are discussed in relation to the
      changes of diamagnetic contribution to the relevant 1H shielding constants. The
      comparison to the literature data for similar complexes containing auxiliary
      ligands other than chlorides exhibited a large dependence of delta1H parameters
      on electron density variations and ring-current effects (inductive and
      anisotropic phenomena). The influence of deviations from planarity, concerning
      either MN2Cl2 chromophores or azine ring systems, revealed by the known X-ray
      structures of [Pd(bquin)Cl2] and [Pt(bquin)Cl2], is discussed in respect to 1H
      NMR spectra. 15N coordination shifts (Delta15Ncoord=delta15Ncomplex
      delta15Nligand) of ca. 78-100 ppm (to lower frequency) are attributed mainly to
      the decrease of the absolute value of paramagnetic contribution in the relevant
      15N shielding constants, this phenomenon being noticeably dependent on the type
      of a platinide metal and coordination sphere geometry. The absolute magnitude of
      Delta15Ncoord parameter increased by ca 15 ppm upon Pd(II)-->Pt(II) replacement
      but decreased by ca. 15 ppm following trans-->cis transition. Experimental 1H,
      13C, 15N NMR chemical shifts are compared to those quantum-chemically calculated
      by B3LYP/LanL2DZ+6-31G**//B3LYP/LanL2DZ+6-31G*, both in vacuo and in CHCl3 or DMF
      solution.

PMID- 18044806
TI  - J(F,H), J(C,H) and J(H,H) couplings involving the individual methyl group protons
      in 1,2,3,4-tetrachloro-5,6,7,8-tetrafluoro-9-methyltriptycene. Evidence of blue
      shifting hydrogen bond.
AB  - 1,2,3,4-tetrachloro-5,6,7,8-tetrafluoro-9-methyltriptycene was studied in NMR
      spectra at low temperatures where the methyl group dynamics is frozen. Values of
      5J(19F,1H), 1J(13C,1H), and 2J(1H,1H) for the individual methyl protons were
      measured. They are in a fair agreement with the corresponding theoretical values
      calculated at a density functional theory (DFT) level. The 5J(19F,1H) couplings
      involve the peri-F nucleus and occur via the 'through space' mechanism. Both the
      natural bond orbital analysis (at a HF level) and the observed pattern of
      1J(13C,1H) coupling values corroborate occurrence in this molecule of
      intramolecular, blue-shifting hydrogen bonds engaging the methyl hydrogens. The
      'through space' 5J(19F,1H) couplings may indicate the routes of electron density
      transfers that escape detection by the natural bond analysis. A consideration of
      these effects can enrich the chemical intuition involving this specific sort of H
      bonds.

PMID- 18044808
TI  - Complete 1H and 13C NMR assignments of three new polyhydroxylated sterols from
      the South China Sea gorgonian Subergorgia suberosa.
AB  - Three new polyhydroxylated sterols, 3beta,6alpha,11,20beta,24-pentahydroxy- 9,11
      seco-5alpha-24-ethylcholest-7,28-diene-9-one (1), 3-(1',2'-ethandiol)-24-
      methylcholest-8(9),22E-diene-3beta,5alpha,6alpha,7alpha,11alpha-pentaol (2), 24
      methylcholest-7,22 E-diene-3beta,5alpha,6beta,25-tetraol (3) together with five
      known sterols, were isolated from the EtOH/CH2Cl2 extract of the South China Sea
      gorgonian Subergorgia suberosa. The complete assignments of the 1H and 13C NMR
      chemical shifts for these new compounds were achieved by means of 1D and 2D NMR
      techniques, including HSQC, HMBC, 1H--1H COSY, and NOESY spectra.

PMID- 18044809
TI  - Complete assignments of 1H and 13C NMR data for trypanocidal eremantholide C
      oxide derivatives.
AB  - The chemical transformations of eremantholide C (1), a trypanocidal sesquiterpene
      lactone isolated from Lychnophora trichocarpha Spreng., gave five new oxide
      derivatives: 3'-hydroxyeremantholide C (2), 1'-formyleremantholide C (3), 1'
      carboxyeremantholide C (4), 1'-carbomethoxyeremantholide C (5) and sodium 1'
      carboxylate of eremantholide C (6). The (1)H and (13)C NMR data of all these
      derivatives were assigned based on 1D and 2D techniques. The derivatives were
      evaluated against Y and CL strains of Trypanosoma cruzi. All of them were
      inactive against the Y strain. Compounds 2 and 5 displayed 100% activity on the
      CL strain while compounds 4 and 6 were partially active on the CL strain.

PMID- 18044810
TI  - 1H and 13C NMR assignments for the sesquiterpene aldehydes, lepidozenal and
      isobicyclogermacrenal, from Eucalyptus dawsonii.
AB  - Lepidozenal and isobicyclogermacrenal were isolated from the leaves of Eucalyptus
      dawsonii and a complete assignment of their 1H and 13C NMR spectra was carried
      out using 2D NMR methods.

PMID- 18044811
TI  - NMR study of hydroxy protons of di- and trimannosides, substructures of Man-9.
AB  - The chemical shifts, temperature coefficients and inter-residual rotating-frame
      Overhauser effect (ROE)s for the hydroxy protons of some alpha-(1,2)-, alpha
      (1,3)- and alpha-(1,6)-linked di- and trimannosides have been measured for
      samples in 85% H2O/15% acetone-d6 solution. These mannosides, Manalpha(1-
      >2)ManalphaOMe (1) Manalpha(1-->3)ManalphaOMe (2), Manalpha(1-->6)ManalphaOMe
      (3), Manalpha(1-->2)Manalpha(1-->2)ManalphaOMe (4), Manalpha(1-->2)Manalpha(1-
      >3)ManalphaOMe (5), Manalpha(1-->2)Manalpha(1-->6)ManalphaOMe (6) and Manalpha(1-
      >3)[Manalpha1-->6]ManalphaOMe (7), are substructures of the N-glycan Man-9. The
      NMR data show that the hydration of each individual hydroxyl group in the di- and
      trisaccharides is very similar to the hydration of the corresponding hydroxyl in
      the monomeric methyl alpha-D-mannoside. No hydrogen-bond interactions were found
      to stabilize the conformations of the alpha-(1,2)- and alpha-(1,6)-linkages and
      the chemical shifts for the hydroxy proton resonances of the alpha-(1,6)-linkage
      indicated high-conformational flexibility. For the alpha-(1,3)-linkage, however,
      the downfield shift for the signal of O(2)H of the 3-substituted residue together
      with the ROE between this proton and H5' on the next residue suggest some weak
      inter-residue interactions.

PMID- 18044812
TI  - Structure-based design of a bicyclic peptide antagonist of the vascular
      endothelial growth factor receptors.
AB  - Dysregulated angiogenesis is implicated in several pathologies, including cancer
      and age-related macular degeneration. A potential antiangiogenic strategy
      consists in developing VEGF receptor ligands capable of preventing VEGF binding
      and the subsequent activation of these receptors. Herein, we describe the
      structure-based design of a VEGF-mimicking peptide, VG3F. This 25-mer peptide was
      doubly cyclized, on-resin, by formation of both a disulfide bridge and an
      intramolecular amide bond to constrain it to adopt a bioactive conformation.
      Tested on in vitro assays, VG3F was able to prevent VEGF binding to VEGF receptor
      1 and inhibit both VEGF-induced signal transduction and cell migration.

PMID- 18044813
TI  - Fertility outcomes following expectant management of tubal ectopic pregnancy.
AB  - OBJECTIVES: To evaluate fertility outcome after the expectant management of tubal
      ectopic pregnancy. METHODS: Our dedicated early pregnancy database was searched
      for all women diagnosed with a tubal ectopic pregnancy between January 1999 and
      June 2003 who were either managed expectantly or underwent a salpingectomy. They
      were contacted to enquire about their ability to conceive following the ectopic
      pregnancy and about the outcomes of any subsequent pregnancies. RESULTS: Four
      hundred and forty-four women had a diagnosis of tubal ectopic pregnancy, and 173
      (39%) were successfully contacted. A total of 146/173 (84.4%; 95% CI, 79-89.8%)
      tried for another pregnancy: 49/59 (83.1%; 95% CI, 73.4-92.6%) in the expectant
      management and 97/114 (85.1%; 95% CI, 78.4-91.6%) in the salpingectomy group (P >
      0.05). Spontaneous intrauterine pregnancy occurred in 41/49 (83.7%; 95% CI, 73.3
      94.2%) women managed expectantly and in 62/97 (63.9%; 95% CI, 54.4-73.5%) women
      managed surgically (odds ratio 2.89; 95% CI, 1.22-6.86%). The risk of recurrent
      ectopic pregnancy was not significantly different between the two management
      groups. CONCLUSIONS: Fertility outcomes following the expectant management of
      tubal ectopic pregnancy are comparable to those following salpingectomy.

PMID- 18044815
TI  - Factors related to institutionalization among disabled older people; a two-year
      longitudinal study.

PMID- 18044814
TI  - The association between activity participation and time to discharge in the
      assisted living setting.
AB  - OBJECTIVES: Given recent evidence that activity participation may reduce
      functional decline, the effect of activity on resident ability to remain in
      assisted living (AL) is of interest. This study examines the relationship between
      participation in activities and the length of time residents remain in AL.
      METHODS: The data reported here were gathered in the initial phase of the
      Maryland Assisted Living Study (MDAL), an epidemiologic study of psychiatric
      disorders in AL. A stratified, random sample of 198 residents of 22 AL facilities
      in central Maryland was evaluated using a number of cognitive, behavioral,
      general health, and functional assessments. The total amount of time each
      resident spent in group and solitary activity in the prior month was quantified.
      The dependent variable, time to discharge (TTD), was the number of days between
      the date of initial assessment by the study team and the date of death in AL,
      discharge, or administrative censoring. RESULTS: Greater levels of activity
      participation at baseline are associated with longer TTD in an univariate Cox
      proportional hazards model. After adjustment for global cognitive functioning,
      general medical health, and mobility, greater activity participation remained
      associated with longer TTD in AL (p=0.017). CONCLUSIONS: Higher levels of
      activity are associated with longer retention in the AL setting. This effect
      appeared to be independent of other potentially confounding factors such as
      general health, cognitive impairment, and mobility. This finding is consistent
      with the hypothesis that engagement in activities delays functional decline, but
      further longitudinal research is needed to understand this finding.

PMID- 18044816
TI  - Microwave-assisted Boc-solid phase peptide synthesis of cyclic cysteine-rich
      peptides.
AB  - In this study we describe the first protocols for the synthesis of cystine-rich
      peptides in the presence of microwave radiation with Boc-solid phase peptide
      synthesis (SPPS). This method is exemplified for macrocyclic peptides known as
      cyclotides, which comprise approximately 30 amino acids and incorporate a cystine
      knot arrangement of their three disulfide bonds. However, the method is broadly
      applicable for a wide range of peptides using Boc-SPPS, especially for SPPS of
      large peptides via native chemical ligation. Microwave radiation produces
      peptides in high yield and with high purity, and we were able to reduce the time
      for the assembly of approximately 30 mer peptide chains to an overnight reaction
      in the automated microwave-assisted synthesis.

PMID- 18044817
TI  - Cartilage tissue engineering using resorbable scaffolds.
AB  - Cartilage tissue engineering holds considerable promise for orthopaedic and
      reconstructive head and neck surgery. With an increasingly ageing population, the
      number of patients affected by arthritis and recurrent joint pain is constantly
      growing, along with the associated socio-economic costs. In head and neck surgery
      reconstructive procedures gain increasing importance in multimodal tumour
      therapies. These procedures require the harvesting of large amounts of donor
      tissue, which causes significant donor site morbidity. Therefore, in vitro
      engineered cartilage may provide for a cost-effective and clinically valuable
      medical need. This article presents an overview of the clinical background as
      well as considerations for engineered cartilage in the head and neck, and
      provides examples of cartilage tissue engineering based on various scaffolds.

PMID- 18044818
TI  - Measure of quality of life for Taiwanese persons with early to moderate dementia
      and related factors.
AB  - BACKGROUND: This study validates the Chinese Dementia-Quality of Life instrument
      (DQoL) in patients with early to moderate stages of Alzheimer's disease (AD)
      (Clinical Dementia Rating Scale, CDR=0.5, 1, and 2; MMSE >or= 12). METHODS: A
      cross-sectional design was used involving 98 participants (27 controls, 35
      patients with questionable dementia (QD), and 36 patients with mild to moderate
      AD) and 51 paired family caregivers (FCs) (20 FCs of QD patients, 31 FCs of AD
      patients). FCs were recruited to evaluate patients' DQoL using the parallel form.
      Internal consistency, construct validity and concurrent validity of the DQoL were
      examined. RESULTS: The findings indicated that the Chinese DQoL instrument has
      stable internal consistency but only moderate validity when used in early to
      moderate AD participants with MMSE greater than, or equal to 12. The DQoL and
      Self-esteem subscales were significantly different across the three dementia
      severity groups. The values of internal consistency of the DQoL and its five
      subscales were high for the ratings of both the patients and the FCs. The
      interscale correlations for the DQoL were almost all significant for patients'
      and FCs' ratings. Agreement of the DQoL and its subscales for patients and FCs
      was significant. However, two inconsistencies were found in the results of the
      factor analysis and the prior conceptualization of patients' DQoL, the subscales
      of Self-esteem and Negative Affect. Global cognitive impairment and self-care
      problems significantly correlated with the patients' DQoL, while the patients'
      depressive symptoms and self-care problems significantly correlated with the FCs'
      DQoL. CONCLUSIONS: The Chinese DQoL reported by early to moderate AD patients has
      good reliability, but moderate validity because the patients' depressive symptoms
      did not correlate with their DQoL and the major subscales. Both patients' and
      FCs' ratings on DQoL are important in research and treatment decision making.

PMID- 18044819
TI  - Mapping the peptide and protein immune response in the larvae of the fleshfly
      Sarcophaga bullata.
AB  - We chose the larvae of fleshfly Sarcophaga bullata to map the peptide and protein
      immune response. The hemolymph of the third-instar larvae of S. bullata was used
      for isolation. The larvae were injected with bacterial suspension to induce an
      antimicrobial response. The hemolymph was separated into crude fractions, which
      were subdivided by RP-HPLC, gel electrophoresis, and free-flow electrophoresis.
      In several fractions, we determined significant antimicrobial activities against
      the pathogenic bacteria Escherichia coli, Staphylococcus aureus, or Pseudomonas
      aeruginosa. Among antimicrobially active compounds we identified dipeptide beta
      alanyl-L-tyrosine, protein transferrin, and two variants of peptide sapecin. We
      also partially characterized two novel antimicrobially active polypeptides;
      odorant-binding protein 99b, and a peptide which remains unidentified.

PMID- 18044820
TI  - Controlled disassembly of peptide amphiphile fibres.
AB  - In this paper, the introduction of both a methionine residue and a nitrobenzyl
      derivative as a labile linker between the peptide part and the hydrophobic alkyl
      chain of a peptide amphiphile are presented. These modifications are shown not to
      inhibit the formation of structured assemblies that analogous peptide amphiphiles
      lacking the linkers are able to form. Moreover, the introduction of either labile
      linker allows removal of the peptide amphiphile's stabilizing hydrophobic
      moieties to initiate a controlled disassembly of fibre aggregates. This is
      achieved by either treatment with CNBr or UV irradiation, respectively. These
      disassembly mechanisms could be the starting point for methodology that allows
      further manipulation of self-assembled peptide amphiphile architectures.

PMID- 18044823
TI  - Automated follicle tracking facilitates standardization and may improve work
      flow.

PMID- 18044824
TI  - Twin-to-twin transfusion syndrome: time to forget the Quintero staging system?

PMID- 18044825
TI  - What understanding of decision-making in prenatal screening could decision
      analysis provide?

PMID- 18044826
TI  - Early manifestations and spectrum of recipient twin cardiomyopathy in twin-twin
      transfusion syndrome: relation to Quintero stage.
AB  - OBJECTIVES: To examine cardiac structural and functional changes in twin-twin
      transfusion syndrome (TTTS), relative to Quintero stage, as a means of evaluating
      the spectrum of cardiomyopathy in TTTS. METHODS: This was a cross-sectional,
      retrospective study of 42 consecutive cases of TTTS referred to a single fetal
      therapy center. Quintero stages were assigned by standard criteria. Presence of
      ventricular hypertrophy, cardiomegaly, atrioventricular valve regurgitation
      (AVVR), ventricular systolic dysfunction and right ventricular outflow tract
      obstruction on fetal echocardiography were noted. The Doppler myocardial
      performance index (MPI), an index of global ventricular function, was calculated
      for both ventricles in subjects with adequate Doppler data. We compared cardiac
      changes across Quintero stages. RESULTS: There was no cardiomyopathy observed in
      donor twins. The majority of subjects presented at Quintero Stage I (n = 14), II
      (n = 14) or III (n = 11), with fewer at Stages IV (n = 2) or V (n = 1). As early
      as Quintero Stages I and II, a significant proportion of recipient twins had
      ventricular hypertrophy (17/28, 61%), AVVR (6/28, 21%) or quantitative
      abnormalities in either right (12/24, 50%) or left (14/24, 58%) ventricular
      function. Increasing prevalence of biventricular systolic dysfunction and
      cardiomegaly accompanied advancing Quintero stage. CONCLUSIONS: Changes in
      cardiac structure and function not reflected in Quintero staging occur in
      recipient twins early in the evolution of TTTS. Incorporation of cardiac findings
      into assessment of TTTS severity may prove useful in stratification of risk and
      treatment selection.

PMID- 18044827
TI  - Extracellular matrix signature identifies breast cancer subgroups with different
      clinical outcome.
AB  - Prediction of the clinical outcome of breast cancer is multi-faceted and
      challenging. There is growing evidence that the complexity of the tumour micro
      environment, consisting of several cell types and a complex mixture of proteins,
      plays an important role in development, progression, and response to therapy. In
      the current study, we investigated whether invasive breast tumours can be
      classified on the basis of the expression of extracellular matrix (ECM)
      components and whether such classification is representative of different
      clinical outcomes. We first examined the matrix composition of 28 primary breast
      carcinomas by morphology and gene expression profiling using 22K oligonucleotide
      Agilent microarrays. Hierarchical clustering of the gene expression profile of
      278 ECM-related genes derived from the literature divided the tumours into four
      main groups (ECM1-4). A set of selected differentially expressed genes was
      validated by immunohistochemistry. The robustness of the ECM classification was
      confirmed by studying the four ECM groups in a previously published gene
      expression data set of 114 early-stage primary breast carcinomas profiled using
      cDNA arrays. Univariate survival analysis showed significant differences in
      clinical outcome among the various ECM subclasses. One set of tumours, designated
      ECM4, had a favourable outcome and was defined by the overexpression of a set of
      protease inhibitors belonging to the serpin family, while tumours with an ECM1
      signature had a poorer prognosis and showed high expression of integrins and
      metallopeptidases, and low expression of several laminin chains. Furthermore, we
      identified three surrogate markers of ECM1 tumours: MARCO, PUNC, and SPARC, whose
      expression levels were associated with breast cancer survival and risk of
      recurrence. Our findings suggest that primary breast tumours can be classified
      based upon ECM composition and that this classification provides relevant
      information on the biology of breast carcinomas, further supporting the
      hypothesis that clinical outcome is strongly related to stromal characteristics.

PMID- 18044828
TI  - Fatty acid, triacylglycerol, and phytosterol composition in six Tunisian olive
      varieties.
AB  - The physicochemical and stability properties as well as the fatty acid,
      triacylglycerol, sterol, and triterpenic dialcohol compositions of Tunisian olive
      oil varieties were analyzed. On the basis of our results, we classified all of
      the monovarietal oils into the extra virgin category. Oleic and linoleic acids
      were the most useful fatty acids to discriminate three cultivars, Neb Jmel,
      Chetoui, and Ain Jarboua, from the others. Of the six monovarietal virgin olive
      oils analyzed, the main triacylglycerols were OOO, POO, PLO plus SLL, and OLO,
      which was expected given the high oleic acid and low linoleic and linolenic acids
      content observed in total fatty acids. In total, these accounted for more than
      80% of the total HPLC chromatogram peak area. The main sterols found were beta
      sitosterol, Delta5-avenasterol, and campesterol. The statistical analysis showed
      significant differences between oil samples, and the obtained results showed a
      great variability in the oil composition between cultivars, which is influenced
      exclusively by genetic factors.

PMID- 18044829
TI  - Changes in structures of milk proteins upon photo-oxidation.
AB  - Changes in protein structures as a result of riboflavin-induced photo-oxidation
      were studied for six milk proteins: alpha-casein, beta-casein, kappa-casein,
      lactoferrin, alpha-lactalbumin, and beta-lactoglobulin. The milk proteins showed
      significant variability in sensitivity to photo-oxidation. After photo-oxidation,
      an increase in carbonyl content because of oxidation of tryptophan, histidine,
      and methionine, as well as formation of dityrosine, was observed for all proteins
      studied, although at very different levels. Generally, the increment was highest
      for alpha- and beta-casein and was lowest for lactoferrin. Loss of tryptophan
      because of photo-oxidation was well-correlated with the formation of the
      tryptophan oxidation products, N-formylkynurenine and kynurenine. Changes at the
      tertiary protein structure level were observed after photo-oxidation of the
      globular proteins, where tryptophan fluorescence emission indicated unfolding of
      alpha-lactalbumin and beta-lactoglobulin, whereas lactoferrin achieved a more
      compact tertiary structure. Changes in secondary structure were observed for
      alpha-lactalbumin and beta-lactoglobulin, whereas the secondary structure of
      lactoferrin did not change. Polymerization of alpha- and beta-casein and of
      lactoferrin was observed, whereas kappa-casein, alpha-lactalbumin, and beta
      lactoglobulin showed little tendency to polymerize after photo-oxidation.
      Lability toward photo-oxidation is discussed according to the structural
      stabilities of the globular proteins.

PMID- 18044830
TI  - Inhibition of ice crystal growth in ice cream mix by gelatin hydrolysate.
AB  - The inhibition of ice crystal growth in ice cream mix by gelatin hydrolysate
      produced by papain action was studied. The ice crystal growth was monitored by
      thermal cycling between -14 and -12 degrees C at a rate of one cycle per 3 min.
      It is shown that the hydrolysate fraction containing peptides in the molecular
      weight range of about 2000-5000 Da exhibited the highest inhibitory activity on
      ice crystal growth in ice cream mix, whereas fractions containing peptides
      greater than 7000 Da did not inhibit ice crystal growth. The size distribution of
      gelatin peptides formed in the hydrolysate was influenced by the pH of
      hydrolysis. The optimum hydrolysis conditions for producing peptides with maximum
      ice crystal growth inhibitory activity was pH 7 at 37 degrees C for 10 min at a
      papain to gelatin ratio of 1:100. However, this may depend on the type and source
      of gelatin. The possible mechanism of ice crystal growth inhibition by peptides
      from gelatin is discussed. Molecular modeling of model gelatin peptides revealed
      that they form an oxygen triad plane at the C-terminus with oxygen-oxygen
      distances similar to those found in ice nuclei. Binding of this oxygen triad
      plane to the prism face of ice nuclei via hydrogen bonding appears to be the
      mechanism by which gelatin hydrolysate might be inhibiting ice crystal growth in
      ice cream mix.

PMID- 18044831
TI  - Antioxidant profiling of native Andean potato tubers (Solanum tuberosum L.)
      reveals cultivars with high levels of beta-carotene, alpha-tocopherol,
      chlorogenic acid, and petanin.
AB  - The antioxidant profile of 23 native Andean potato cultivars has been
      investigated from a human nutrition perspective. The main carotenoid and
      tocopherol compounds were studied using high-performance liquid chromatography
      coupled with a diode array detector (HPLC-DAD) and a fluorescence detector,
      respectively, whereas polyphenols (including anthocyanins in colored tubers) were
      identified by means of both HPLC-mass spectrometry and HPLC-DAD. Antioxidant
      profiling revealed significant genotypic variations as well as cultivars of
      particular interest from a nutritional point of view. Concentrations of the
      health-promoting carotenoids, lutein and zeaxanthin, ranged from 1.12 to 17.69
      microg g(-1) of dry weight (DW) and from 0 to 17.7 microg g(-1) of DW, with
      cultivars 704353 and 702472 showing the highest levels in lutein and zeaxanthin,
      respectively. Whereas beta-carotene is rarely reported in potato tubers,
      remarkable levels of this dietary provitamin A carotenoid were detected in 16
      native varieties, ranging from 0.42 to 2.19 microg g(-1) of DW. The amounts of
      alpha-tocopherol found in Andean potato tubers, extending from 2.73 to 20.80
      microg g(-1) of DW, were clearly above the quantities generally reported for
      commercial varieties. Chlorogenic acid and its isomers dominated the polyphenolic
      profile of each cultivar. Dark purple-fleshed tubers from the cultivar 704429
      contained exceptionally high levels of total anthocyanins (16.33 mg g(-1) of DW).
      The main anthocyanin was identified as petanin (petunidin-3-p-coumaroyl
      rutinoside-5-glucoside). The results suggest that Andean potato cultivars should
      be exploited in screening and breeding programs for the development of potato
      varieties with enhanced health and nutritional benefits.

PMID- 18044832
TI  - Phytotoxic Eremophilanes from Ligularia macrophylla.
AB  - Systematic bioassay-guided fractionation of the methylene chloride extract of the
      roots from Ligularia macrophylla was performed to identify both phytotoxic and
      antifungal compounds. Four phytotoxic eremophilanes (furanoeremophilan
      14beta,6alpha-olide, 6beta-angeloyloxy-10beta-hydroxyfuranoeremophilane,
      eremophil-7(11)-ene-12,8alpha;14beta,6alpha-diolide, and 3alpha
      angeloyloxybakkenolide A) and two antifungal fatty acids (linoleic acid and alpha
      linolenic acid) were isolated. The X-ray crystal structure determination of 6beta
      angeloyloxy-10beta-hydroxyfuranoeremophilane is reported here for the first time.
      All four eremophilanes substantially inhibited growth of the monocot Agrostis
      stolonifera (bentgrass) while demonstrating little activity against the dicot
      Lactuca sativa (lettuce) at 1000 microM. In a dose-response screening of all
      compounds for growth inhibitory activity against Lemna paucicostata, 6beta
      angeloyloxy-10beta-hydroxyfuranoeremophilane was the most active with an IC50 of
      2.94+/-0.16 microM. This compound also caused the greatest reduction of
      photosynthetic electron flow; however, its mode of action remains to be
      determined. Evaluation of isolated compounds for activity against the Formosan
      subterranean termite, Coptotermes formosanus, is also reported. At a
      concentration of 0.5% (wt/wt), 6beta-angeloyloxy-10beta-hydroxyfuranoeremophilane
      significantly reduced the consumption of filter paper by C. formosanus.

PMID- 18044833
TI  - Protective effect of selenium in Broccoli (Brassica oleracea) plants subjected to
      cadmium exposure.
AB  - The protective effect of selenium against the cadmium-induced oxidative effect in
      broccoli ( Brassica oleracea) plants was studied. Plants grown in hydroponic
      culture were supplied with selenium [as Se(IV)] and cadmium [as Cd(II)],
      individually or simultaneously. Cadmium accumulation in roots was noticeably
      higher than in the aerial parts of the plants, and this effect was even more
      acute when selenium was simultaneously added. Cadmium phytotoxicity was evidenced
      by an increase in the malondialdehyde (MDA) concentration in the roots and a
      decrease of photosynthetic pigment and tocopherol concentration in the aerial
      parts of the plant. The simultaneous addition of selenium alleviated cadmium
      induced stress in the roots after 40 days of exposition. In the leaves, a more
      remarkable decrease of tocopherol and chlorophyll concentration was observed in
      the cadmium-enriched plants after 10 days of exposure. The results provided
      evidence that selenium supplementation helps the plant to minimize the cadmium
      oxidant effect. Tocopherol concentration in broccoli fruit of cadmium-supplied
      plants was not affected in comparison to control. However, the proportion of
      alpha-tocopherol increases with the addition of selenium. This response is
      important not only for the protective effect against oxidative damage in the
      plant but also in terms of human nutrition.

PMID- 18044834
TI  - Free and conjugated phytosterols in cured tobacco leaves: influence of genotype,
      growing region, and stalk position.
AB  - Although phytosterols in tobacco leaves have specific effects on tobacco quality,
      there is little research on the distribution of free and conjugated phytosterols
      in various tobacco leaves. In this paper, we explored the content and composition
      of phytosterols in representative cured tobacco leaves by gas chromatography of
      TMS-ether derivatives. We found that phytosterol contents in tobacco leaves
      ranged from 1.0 to 2.5 mg/g of dried leaf tissue, depending on different types of
      tobacco leaves. The majority of phytosterols (75-85%) were conjugated as ester
      and glycosides, with only about 15-25% existing in the free form. Furthermore,
      the genetic variability gives rise to the significant differences among different
      tobacco types with phytosterol levels: the contents of phytosterols in tobacco
      leaves decreased in the order of flue-cured tobacco, Oriental tobacco, Burley
      tobacco, cigar tobacco, and Maryland tobacco. At the same time, the tobacco
      curing process leads to a difference in phytosterol existing-form distribution in
      some variation laws.

PMID- 18044835
TI  - NMR signal analysis to characterize solid, aqueous, and lipid phases in baked
      cakes.
AB  - Proton mobility was studied in molecular fractions of some model systems and of
      cake using a 1H nuclear magnetic resonance (NMR) relaxation technique. For cake,
      five spin-spin relaxation times (T2) were obtained from transverse relaxation
      curves: T2 (1) approximately 20 micros, T2 (2) approximately 0.2 ms, T2 (3)
      approximately 3 ms, T2 (4) approximately 50 ms, and T2 (2) approximately 165 ms.
      The faster component was attributed to the solid phase, components 2 and 3 were
      associated with the aqueous phase, and the two slowest components were linked to
      the lipid phase. After cooking, the crust contained more fat but less water than
      the center part of the cake. The amount of gelatinized starch was lower in the
      crust, and water was more mobile due to less interaction with macromolecules.
      This preliminary study revealed different effects of storage on the center and
      crust.

PMID- 18044836
TI  - Alpha-chaconine-reduced metastasis involves a PI3K/Akt signaling pathway with
      downregulation of NF-kappaB in human lung adenocarcinoma A549 cells.
AB  - Alpha-chaconine, isolated from Solanum tuberosum Linn., is a naturally occurring
      steroidal glycoalkaloid in potato sprouts. Some reports demonstrated that alpha
      chaconine had various anticarcinogenic properties. The aim of this study is to
      investigate the inhibitory effect of alpha-chaconine on lung adenocarcinoma cell
      metastasis in vitro. We chose the highly metastatic A549 cells, which were
      treated with various concentrations of alpha-chaconine to clarify the potential
      of inhibiting A549 cells invasion and migration. Data showed that alpha-chaconine
      inhibited A549 cell invasion/migration according to wound healing assay and
      Boyden chamber assay. Our results also showed that alpha-chaconine could inhibit
      phosphorylation of c-Jun N-terminal kinase (JNK) and Akt, whereas it did not
      affected phosphorylation of extracellular signal regulating kinase (ERK) and p38.
      In addition, alpha-chaconine significantly decreased the nuclear level of nuclear
      factor kappa B (NF-kappaB) and the binding ability of NF-kappaB. These results
      suggested that alpha-chaconine inhibited A549 cell metastasis by a reduction of
      matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9)
      activities involving suppression of phosphoinositide 3-kinase/Akt/NF-kappaB
      (PI3K/Akt/NF-kappaB) signaling pathway. Inhibiting metastasis by alpha-chaconine
      might offer a pivotal mechanism for its effective chemotherapeutic action.

PMID- 18044837
TI  - Strong increase of foliar inulin occurs in transgenic lettuce plants (Lactuca
      sativa L.) overexpressing the Asparagine Synthetase A gene from Escherichia coli.
AB  - Transgenic lettuce (Lactuca sativa L. cv. 'Cortina') lines expressing the
      asparagine synthetase A gene from Escherichia coli were produced to alter the
      plant nitrogen status and eventually enhance growth. The relative molecular
      abundance of water-soluble metabolites was measured by 1H NMR in transgenic and
      conventional plants at early developmental stages and grown under the same
      conditions. NMR metabolic profiles assessed that a transgenic line and the wild
      type counterpart shared the same compounds, but it also revealed side effects on
      the carbon metabolism following genetic modification. Concerning the nitrogen
      status, the amino acid content did not vary significantly, except for glutamic
      acid and gamma-aminobutyric acid, which diminished in the transgenics. As for the
      carbon metabolism, in transgenic leaves the contents of sucrose, glucose, and
      fructose decreased, whereas that of inulin increased up to 30 times, accompanied
      by the alteration of most Krebs's cycle organic acids and the rise of tartaric
      acid compared to nontransformed controls. Lettuce leaf inulins consisted of short
      oligomeric chains made of one glucose unit bound to two/four fructose units.
      Inulins are beneficial for human health, and they are extracted from plants and
      commercialized as long-chain types, whereas the short forms are synthesized
      chemically. Hence, lettuce genotypes with high content of foliar short-chain
      inulin represent useful materials for breeding strategies and a potential source
      for low molecular weight inulin.

PMID- 18044838
TI  - Changes and roles of secondary structures of whey protein for the formation of
      protein membrane at soy oil/water interface under high-pressure homogenization.
AB  - The conformational changes of whey proteins upon adsorption at the soy oil/water
      interface were investigated using Fourier transform infrared (FT-IR)
      spectroscopy. Significant changes were observed in the bands assigned to beta
      sheets and alpha-helix structures following the adsorption of proteins at the
      oil/water interface. The remaining interfacial proteins after Tween 20 desorption
      revealed small changes in beta-sheet and alpha-helical structures, whereas in the
      desorbed whey proteins the unordered structures largely increased, and beta-sheet
      structures almost disappeared. These FT-IR results provide important knowledge
      about the conformational modifications in whey proteins occurring upon adsorption
      at the oil/water interface. Finally, specific conformational changes are
      necessary to stabilize emulsions: adsorption-induced unfolding, increase in alpha
      helical structures to establish interactions with the oil phase, and aggregation
      between adsorbed whey proteins to form protein membranes. Moreover, the
      structural changes in whey protein adsorbed at the oil/water interface under high
      pressure homogenization are irreversible.

PMID- 18044839
TI  - Mono- and Di-sesquiterpenoids from Chloranthus spicatus.
AB  - Three new dimeric sesquiterpenoids, chloramultilides B-D ( 1- 3), along with 10
      known sesquiterpenoids, were isolated from the whole plant of Chloranthus
      spicatus. Their structures were established by physical data (1D and 2D NMR, MS).
      The structure and absolute configuration of 1 was confirmed by X-ray
      crystallography. Compound 1 exhibited moderate in vitro antifungal activity.

PMID- 18044840
TI  - Tauramamide, a lipopeptide antibiotic produced in culture by Brevibacillus
      laterosporus isolated from a marine habitat: structure elucidation and synthesis.
AB  - Tauramamide (1), a new lipopeptide antibiotic, is produced by cultures of the
      marine bacterial isolate Brevibacillus laterosporus PNG276 obtained from Papua
      New Guinea. Tauramamide was isolated as its methyl and ethyl esters 2 and 3,
      whose structures were elucidated by analysis of NMR, MS, and chemical degradation
      data. A total synthesis of tauramamide (1) and tauramamide ethyl ester (3)
      confirmed the structure proposed from spectroscopic analysis and provided the
      natural product for antimicrobial testing. Tauramamide (1) and ethyl ester 3 show
      potent and relatively selective inhibition of pathogenic Enterococcus sp.

PMID- 18044841
TI  - Chlorocyclinones A-D, chlorinated angucyclinones from Streptomyces sp. strongly
      antagonizing rosiglitazone-induced PPAR-gamma activation.
AB  - In the course of our screening to identify novel PPAR-gamma modulators for the
      potential treatment of type 2 diabetes, four new chlorinated angucyclinones,
      chlorocyclinones A-D ( 1- 4), were isolated from the mycelium of Streptomyces sp.
      strain DSM 17045. Their structures were established by spectroscopic methods.
      Chlorocyclinones antagonize rosiglitazone-induced peroxisome proliferator
      activated receptor gamma (PPAR-gamma) activation with IC 50's < 0.4 microM in
      vitro using an AlphaScreen assay and are able to displace rosiglitazone from the
      PPAR-gamma ligand-binding domain (LBD) in a scintillation proximity assay (SPA).
      The compounds proved to be active in a cell-based reporter gene assay as well,
      antagonizing rosiglitazone-induced PPAR-gamma activity with IC 50 values between
      0.60 and 7.0 microM. Chlorocyclinone C ( 3) exhibited the most potent activity in
      all assays.

PMID- 18044842
TI  - Serinocyclins A and B, cyclic heptapeptides from Metarhizium anisopliae.
AB  - Two new cyclic heptapeptides, serinocyclins A (1) and B (2), were isolated from
      conidia of the entomopathogenic fungus Metarhizium anisopliae. Structures were
      elucidated by a combination of mass spectrometric, NMR, and X-ray diffraction
      techniques. Serinocyclin A (1) contains three serine units, a hydroxyproline
      (Hyp), a beta-alanine (beta-Ala), and two uncommon nonproteinogenic amino acids,
      1-aminocyclopropane-1-carboxylic acid (Acc) and gamma-hydroxylysine (HyLys). The
      peptide sequence established for 1 by NMR is cyclo-(Acc-Hyp-Ser1-HyLys-beta-Ala
      Ser2-Ser3). Serinocyclin B (2) has Lys in place of the HyLys unit found in 1.
      Chiral amino acid analysis indicated the presence in both compounds of one (2 S,4
      R)-Hyp, two L-Ser, and one D-Ser residue. A Lys found in the hydrolyzate of 2 was
      established as D-configured. A crystal structure of 1 established the position of
      the D-Ser (Ser2) and the absolute configuration of the HyLys unit (2 R,4 S). The
      absence of methyl groups is unusual among fungal peptides and, along with the
      charged lysyl side chain and multiple hydroxyl groups, contributes to the polar
      nature of the compounds. Serinocyclin A produced a sublethal locomotory defect in
      mosquito larvae at an EC 50 of 59 ppm.

PMID- 18044843
TI  - Inhibitory effects of diterpenoid alkaloids on the growth of A172 human malignant
      cells.
AB  - The cytotoxicity against A172 human malignant glioma cells was examined for 14
      alkaloids from the roots of Aconitum yesoense var. macroyesoense and of Aconitum
      japonicum and from the seeds of Delphinium elatum as well as for 25 semisynthetic
      derivatives. The major alkaloid constituents of A. yesoense var. macroyesoense,
      kobusine (2) and pseudokobusine (3), a minor alkaloid constituent of A.
      japonicum, aljesaconitine A (5), and six alkaloid derivatives, N-deethyldelcosine
      (10), N-deethyldelsoline (11), 12-benzoylluciculine (18), 12-anisoylluciculine
      (19), 6,11-dibenzoylpseudokobusine (28), and 6-veratroylpseudokobusine (29), had
      only very weak activity. Four acylated alkaloid derivatives, 12-acetylluciculine
      (23), 11-veratroylpseudokobusine (30), 11-(m
      trifluoromethylbenzoyl)pseudokobusine (32), and 11-(m
      trifluoromethylbenzoyl)kobusine (39), exhibited more potent activity, while
      pseudokobusine 11-cinnamoate (31), 11-anisoate (33), and 11-p-nitrobenzoate (34)
      were found to be the most potent cytotoxic agents.

PMID- 18044844
TI  - (13)C-(15)N correlation via unsymmetrical indirect covariance NMR: application to
      vinblastine.
AB  - Unsymmetrical indirect covariance processing methods allow the derivation of
      hyphenated 2D NMR data from the component 2D spectra, potentially circumventing
      the acquisition of the much lower sensitivity hyphenated 2D NMR experimental
      data. Calculation of HSQC-COSY and HSQC-NOESY spectra from GHSQC, COSY, and NOESY
      spectra, respectively, has been reported. The use of unsymmetrical indirect
      covariance processing has also been applied to the combination of (1)H- (13)C
      GHSQC and (1)H- (15)N long-range correlation data (GHMBC, IMPEACH, or CIGAR
      HMBC). The application of unsymmetrical indirect covariance processing to spectra
      of vinblastine is now reported, specifically the algorithmic extraction of (13)C-
      (15)N correlations via the unsymmetrical indirect covariance processing of the
      combination of (1)H- (13)C GHSQC and long-range (1)H- (15)N GHMBC to produce the
      equivalent of a (13)C- (15)N HSQC-HMBC correlation spectrum. The elimination of
      artifact responses with aromatic solvent-induced shifts (ASIS) is shown in
      addition to a method of forecasting potential artifact responses through the
      indirect covariance processing of the GHSQC spectrum used in the unsymmetrical
      indirect covariance processing.

PMID- 18044846
TI  - Analysis and optimization of nonequilibrium capillary electrophoresis of alpha
      fetoprotein isoforms.
AB  - The L3 isoform of alpha-fetoprotein (AFP) is a specific marker for hepatocellular
      carcinoma. The separation and quantitation of L3 isoform from the L1 isoform is
      facilitated by Lens culinaris agglutin (LCA) affinity of the L3 isoform. The
      affinity-based separation is characterized by nonequilibrium conditions since
      electrophoresis perturbs the species concentrations away from equilibrium. The
      design of such separations requires careful consideration of the interplay
      between the reaction, diffusion, and separation time scales. We performed
      experiments to investigate the effect of separation parameters such as LCA
      concentration and CE voltage on the L1-L3 separation dynamics. We also describe a
      comprehensive mathematical model to predict electropherograms for affinity-based
      separations. The model includes the effects of molecular diffusion,
      electromigration, nonequilibrium reaction, and detection process. Together, the
      results demonstrate a process by which to optimize the affinity-based separations
      of AFP isoforms. We also obtained the kinetic rate constants for LCA affinity
      (kon=1.6x10(3) mol(-1) s(-1) L, koff=1x10(-3) s(-1)) by comparing the model
      predictions with experimental data. This study provides insight into the physics
      of affinity-based separations and can be extended to describe and optimize other
      nonequilibrium CE systems.

PMID- 18044847
TI  - TOF-SIMS analysis of a 576 micropatterned copolymer array to reveal surface
      moieties that control wettability.
AB  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used in a high
      throughput fashion to obtain mass spectra from the surfaces of 576 novel acrylate
      based polymers, synthesized using a combinatorial approach and in a
      micropatterned format. To identify variations in surface chemistry within the
      library, principal component analysis (PCA) was used. PCA clearly identified
      surface chemical commonality and differences within the library. The TOF-SIMS
      spectra were also used to determine the relationship between water contact angle
      (WCA) and the surface chemistry of the polymer library using partial least
      squares regression (PLS). A good correlation between the TOF-SIMS data from the
      novel polymers and water contact angle was obtained. Examination of the PLS
      regression vector allowed surface moieties that correlate with high and low WCA
      to be identified. This in turn provided an insight into molecular structures that
      significantly influence wettability. This study demonstrates that multivariate
      analysis can be successfully applied to TOF-SIMS data from a large library of
      samples and highlights the potential of these techniques for building complex
      surface property/chemistry models.

PMID- 18044848
TI  - Mechanism of thiol oxidation by the superoxide radical.
AB  - In spite of the large quantity of experimental work that deals with the oxidation
      of thiols by superoxide, the mechanism of this reaction is still controversial.
      The ab initio molecular orbital calculations reported here predict that the main
      reaction pathway includes the formation of a three-electron-bonded adduct
      followed by the elimination of the hydroxide anion, giving the sulfinyl radical
      as the reaction product. The alternative reaction pathway consisting of hydrogen
      atom transfer from the thiol to the protonated superoxide radical involves a
      reaction energy barrier that is significantly higher. The difference between the
      two reaction energy barriers is clearly beyond the expected computational
      uncertainty. The systematic scanning of the potential energy surface reveals no
      other competitive reaction pathways. The present results provide a useful basis
      for the interpretation of the complex experimental data related to thiol
      oxidation by superoxide radical in a biological environment.

PMID- 18044849
TI  - Computational study of the enthalpies of formation, DeltafH degrees, and mean
      bond enthalpies, mBEs, of H4-nEXn0/- and H3-nEXn+/0 (E=C, B; X=F-I).
AB  - To compensate for lacking experimental standard enthalpies of formation DeltafH
      degrees of haloboranes/-boranates as well as the isoelectronic halocarbenium ions
      and halomethanes, high-level quantum chemical calculations up to the ccsd(t)/(SDB
      )aug-cc-pVQZ level have been performed to establish these values. Very reliable
      experimental data (e.g., DeltafH degrees of HCl, F, and CH4) or at the G3 level
      established values (e.g., DeltafH degrees of CF3+=410 kJ mol(-1)) were used as
      anchor points to obtain accurate absolute DeltafH degrees and mean bond enthalpy
      (mBE) values. To further minimize systematic errors of the protocol, all derived
      quantities were assessed in isodesmic reactions at the G3 and ccsd(t) level using
      the (SDB-)aug-cc-PVTZ basis set. The obtained DeltafH degrees values are in very
      good agreement to (scarcely available) accurate experimental and computational
      data. Almost all B-containing compounds have been assessed for the first time. We
      derived "best" DeltafH degrees values and used them to determine the mean E-X
      bond enthalpies in H4-nEXn-/0 and H3-nEXn0/+ (with n=1-3, E=B, C, and X=F-I). In
      each of the series, the DeltafH degrees values increase from fluorine to iodine,
      and except for the iodine-containing carbenium ions and the bromo- and
      iodomethanes, the DeltafH degrees values become lower with the more halogen atoms
      that are present in the particle. The boron containing species always have a
      lower DeltafH degrees than the isoelectronic carbenium ions and methanes, and the
      H4-nEXn-/0 are lower in energy than the parent H3-nEXn+/0. This reflects the
      greater average B-X bond strengths.

PMID- 18044850
TI  - Adipic and malonic acid aqueous solutions: surface tensions and saturation vapor
      pressures.
AB  - The surface tension of adipic aqueous solutions was measured as a function of
      temperature (T=278-313 K) and adipic acid mole fraction (X=0.000-0.003) using the
      Wilhelmy plate method. A parametrization fitted to these data is presented. The
      evaporation rates of binary water-malonic and water-adipic acid droplets were
      measured with a TDMA technique at different temperatures (T=293-300 K) and
      relative humidities (58-80%), and the saturation vapor pressures of subcooled
      liquid malonic and adipic acids were derived from the data using a binary
      evaporation model. The temperature dependence of the vapor pressures was obtained
      as least-squares fits to the derived vapor pressures: ln(Psat,l) (Pa)=220.2389
      22634.96/T (K)-26.66767 ln T (K) for malonic acid and ln(Psat,l) (Pa)=140.6704
      18230.97/T (K)-15.48011 ln T (K) for adipic acid.

PMID- 18044851
TI  - Scaling in nonstationary voltammetry representations.
AB  - Despite the widespread use of voltammetry for a range of chemical, biological,
      environmental, and industrial applications, there is still a lack of
      understanding regarding the functionality between the applied voltage and the
      resulting patterns in the current response. This is due to the highly nonlinear
      relation between the applied voltage and the nonstationary current response,
      which casts a direct association nonintuitive. In this Article, we focus on large
      amplitude/high-frequency ac voltammetry, a technique that has shown to offer
      increased voltammetric detail compared to alternative methods, to study
      heterogeneous electrochemical reaction-diffusion cases using a nonstationary time
      series analysis, the Hilbert transform, and symmetry considerations. We show that
      application of this signal processing technique minimizes the significant
      capacitance contribution associated with rapid voltammetric measurements. From a
      series of numerical simulations conducted for different voltage excitation
      parameters as well as kinetic, thermodynamic, and mass transport parameters, a
      number of scaling laws arise that are related to the underlying
      parameters/dynamics of the process. Under certain conditions, these observations
      allow the determination of all underlying parameters very rapidly, experiment
      duration typically<or=1 s, using standard electrode geometries and without any a
      priori assumptions regarding their value. The theoretical results derived from
      this analysis are compared to experiments with an outer-sphere electron-transfer
      species, Ru(NH3)6(2+/3+), on different electrode materials, and the determined
      parameters are in excellent agreement with published values.

PMID- 18044852
TI  - Theoretical study of reaction mechanisms of OH radical with toluene 1,2-epoxide/2
      methyloxepin.
AB  - In this study, the reaction mechanism of toluene 1,2-epoxide/2-methyloxepin with
      OH radical was studied by means of quantum chemical computations performed using
      B3LYP/6-31G(d,p), B3LYP/6-311G(2df,2p), and BHandHLYP/6-31G(d,p) methods. Ground
      state, intermediate, and transition states were determined. The results indicated
      that the 2-methyloxepin, A, isomer is more stable, by 2.4 kcal/mol, than toluene
      1,2-epoxide, B. Two reaction pathways were studied, RP-A and RP-B, corresponding
      to the reaction of OH with toluene 1,2-epoxide and 2-methyloxepin, respectively.
      The localization of a pre-reactive complex for RP-A is crucial for the accurate
      estimation of the rate constant, k=1.0x10(-10) cm3 molecule(-1) s(-1), which is
      in good agreement with that determined experimentally, whereas for RP-B the rate
      constant is 1.3x10(-14) cm3 molecule(-1) s(-1). Under atmospheric conditions,
      both pathways yield 6-oxohepta-2,4-dienal as a main product, and from the
      energetic and kinetic results it was found that RP-A is the preferred pathway.
      The study of the oxide/oxepin mechanism is relevant because, aside from its
      relatively high concentration in the troposphere, this compound has carcinogenic
      and mutagenic properties.

PMID- 18044853
TI  - A Monte Carlo study of isomers and structural evolution in benzene-cyclohexane
      clusters: (C6H6)(C6H12)n, n=3-7, 12.
AB  - Monte Carlo simulated annealing strategies, carried out on four different
      potential energy surfaces, are applied to benzene-cyclohexane clusters, BCn, n=3
      7, 12, to identify low-energy isomers and to trace the evolution of structures as
      a function of cluster size. Initial structures are first heated to ensure
      randomization, and subsequent annealing yields optimized rigid, low-energy
      clusters. Five major structural isomers are identified for BC3: one assumes the
      form of a symmetric, modified sandwich; the remaining four lack general symmetry,
      assuming distorted tetrahedral arrangements. For BC4 and larger clusters, the
      number of low-temperature isomers is large. It is, nevertheless, feasible to
      classify isomers into groups based on structural similarities. The evolution of
      BCn structures as a function of cluster size is observed to follow one of two
      primary paths: The first maximizes benzene-cyclohexane interactions and places
      benzene in or near the BCn cluster center; the competing path maximizes
      cyclohexane-cyclohexane interactions and distances benzene from the cluster's
      center of mass. Results for BC3 and BC4 are discussed with reference to
      experimental results and models previously applied to interpret benzene-argon
      cluster spectra.

PMID- 18044854
TI  - Optical energy transport and interactions between the excitations in a coumarin
      perylene bisimide dendrimer.
AB  - Energy transfer properties of novel coumarin-perylene bisimide dendrimer are
      studied by means of steady state and time-resolved UV/vis spectroscopy. At low
      donor excitation density fast (transfer rate approximately 10 ps(-1)) and
      efficient (quantum yield approximately 99.5%) donor-acceptor energy transfer is
      observed. The random distributions of donor-acceptor orientations and distances
      result in nonexponential energy transfer kinetics. The energy transfer remains
      independent of excitation density up to densities corresponding to one absorbed
      photon per 10 dendrimer molecules. At higher excitation densities the transfer
      rate is found to increase due to excitation of multiple donors per dendrimer.
      Control of the donor-acceptor energy transfer rate is achieved by pre-excitation
      of the acceptor and monitored by prepump-pump-probe experiments, which show that
      the energy transfer rate can be decreased by a factor of 2. The relative
      orientations of transition dipole moments in the donor and acceptor molecules are
      found to be one of the key factors determining the energy transfer dynamics at
      high excitation densities.

PMID- 18044855
TI  - Use of virtual screening, flexible docking, and molecular interaction fields to
      design novel HMG-CoA reductase inhibitors for the treatment of
      hypercholesterolemia.
AB  - Dietary changes associated with drug therapy can reduce high serum cholesterol
      levels and dramatically decrease the risk of coronary artery disease, stroke, and
      overall mortality. Statins are hypolipemic drugs that are effective in the
      reduction of cholesterol serum levels, attenuating cholesterol synthesis in liver
      by competitive inhibition regarding the substrate or molecular target HMG-CoA
      reductase. We have herewith used computer-aided molecular design tools, i.e.,
      flexible docking, virtual screening in large data bases, molecular interaction
      fields to propose novel potential HMG-CoA reductase inhibitors that are promising
      for the treatment of hypercholesterolemia.

PMID- 18044856
TI  - Oligothiophene dendrimers as new building blocks for optical applications.
AB  - Thiophene branched structures have been proposed as candidates for photon
      harvesting and electron-hole transporting materials in novel organic light
      emitting diodes and solar energy conversion devices. To understand the
      photoinduced processes in a novel thiophene dendrimer system, the excited state
      dynamics and nonlinear optical properties of 3D oligothiophene dendrimers have
      been investigated. The key point of this contribution is that we have found that
      with these thiophene dendrimer systems, the excitation is delocalized over a
      large number of thiophene units in the dendrimer and there is an ultrafast energy
      transfer (200-300 fs) to the longest branch of dendrimer, which can be utilized
      for future optical devices. In terms of nonlinear optics, it was found that a
      super-linear increase of two-photon absorption cross-section is observed with an
      increase in thiophene dendrimer generation that can be explained by the increased
      excitation delocalization. Generation dependent torsional energy redistribution
      has also been observed, which planarizes the final emissive state on a picosecond
      time scale.

PMID- 18044857
TI  - Conductance of a cobalt(II) terpyridine complex based molecular transistor: a
      computational analysis.
AB  - A recent experiment, in which a molecular transistor based on the coordination
      chemistry of cobalt(II) and organic self-assembled monolayers is formed by means
      of self-aligned lithography,2 is analyzed with a computational approach. The
      calculations reveal that a complex involving two cobalt(II) ions bridged by
      acetate ions can effectively span the nanogap. This bridged complex is shown to
      be both more flexible and more conductive than the alternative structure
      involving a single cobalt(II) ion. The single cobalt(II) ion complex is the more
      stable structure in a nonconfined environment (i.e., in solution) but is found to
      be less effective at connecting the leads of the fabricated gap and is less
      likely to result in a conductive device.

PMID- 18044858
TI  - Manipulation and characterization of aqueous sodium dodecyl sulfate/sodium
      chloride aerosol particles.
AB  - Aerosol optical tweezers coupled with Raman spectroscopy can allow the detailed
      investigation of aerosol dynamics. We describe here measurements of the evolving
      size, composition, and phase of single aqueous aerosol droplets containing the
      surfactant sodium dodecyl sulfate and the inorganic salt sodium chloride. Not
      only can the evolving wet particle size be probed with nanometer accuracy, but we
      show that the transition to a metastable microgel particle can be followed,
      demonstrating that optical tweezers can be used to manipulate both spherical and
      non-spherical aerosol particles. Further, through the simultaneous manipulation
      and characterization of two aerosol droplets of different composition in two
      parallel optical traps, the phase behavior of a surfactant-doped particle and a
      surfactant-free droplet can be compared directly in situ. We also illustrate that
      the manipulation of two microgel particles can allow studies of the coagulation
      and interaction of two solid particles. Finally, we demonstrate that such
      parallel measurements can permit highly accurate comparative measurements of the
      evolving wet particle size of a surfactant-doped droplet with a surfactant-free
      droplet.

PMID- 18044859
TI  - Adiabatic capture theory applied to N+NH-->N2+H at low temperature.
AB  - The adiabatic capture centrifugal sudden approximation (ACCSA) has been applied
      to the ground state reaction N+NH-->N2+H over the temperature range 2-300 K using
      an existent potential energy surface. The resultant thermal rate constants are in
      agreement with available rate constants from quasi-classical trajectory
      calculations but are significantly larger than the available experimentally
      derived rate. The calculated rate constants monotonically increase with
      increasing temperature but could only be approximately described with a simple
      Arrhenius-like form. Subtle quantum effects are evident in the initial rotational
      state resolved cross sections and rate constants.

PMID- 18044860
TI  - Mesoscopic simulation on phase behavior of pluronic P123 aqueous solution.
AB  - As a new dynamic density functional method, the mesoscopic dynamics (MesoDyn) is
      used to simulate the microphase separation of the binary mixture of tri-block
      copolymer P123 ((EO)20(PO)70(EO)20) and water. With a simple copolymer model,
      various aggregate structures of P123 in water including the micelle, hexagonal,
      and lamellar phases are produced, which can partly reproduce most experimental
      phase regions. The simulated phase ranges are more or less different from those
      established from experiment, especially at high polymer concentrations. This can
      be attributed to different phase mapping situations, that is, the constant shear
      used in simulation versus the varied external forces in experiment. The
      calculated trend for micelle size change in diluted region is co-incident well
      with previous observations in other Pluronic systems. The poly(propylene oxide)
      (PO) block amount is found to influence not only the aggregate morphology but
      also its formation rate in solution. Obtained results indicate that the
      mesoscopic simulation is a valuable tool to supplement the experimental study on
      aggregates formation.

PMID- 18044861
TI  - Phase transition of individually addressable microstructured membranes visualized
      by imaging ellipsometry.
AB  - The phase transition of individually addressable microstructured lipid bilayers
      was investigated by means of imaging ellipsometry. Microstructured bilayers were
      created on silicon substrates by micromolding in capillaries, and the
      thermotropic behavior of various saturated diacyl phosphatidylcholine (1,2
      dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipentadecoyl-sn-glycero-3
      phosphocholine, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)) bilayers
      as well as DMPC/cholesterol membranes was determined by measuring the area
      expansion and thickness of the bilayer as a function of temperature. We found an
      increase in the main phase transition temperature T(M) of 2-6 degrees C and a
      substantially reduced cooperativity compared to multilamellar vesicles.
      Measurements of lateral diffusion constants D employing fluorescence recovery
      after photobleaching revealed, however, only a marginal decrease in D compared to
      those found for vesicles and multibilayers. The known dependencies of T(M) both
      on the chain length of diacyl PC membranes and on the cholesterol content were
      reproduced on a solid support. Microstructured bilayers offer the unique
      advantage of integrating an internal standard of known thermotropic properties,
      which turned out to be important for reducing the measurement error and for
      ruling out the slightly changing impact of the surface on the phase transition
      behavior due to the surface pretreatment.

PMID- 18044862
TI  - Influence of the roughness, topography, and physicochemical properties of
      chemically modified surfaces on the heterogeneous nucleation of protein crystals.
AB  - In this study, the influence of some factors on the heterogeneous nucleation of
      hen egg-white lysozyme (E.C. 3.2.1.17) on a series of chemically modified
      surfaces has been investigated. Microbatch crystallization experiments were
      conducted on the microscope glass slides that were treated with poly-L-glutamic
      acid (PLG), poly(2-hydroxyethyl methacrylate) (P2HEMA), poly(methyl methacrylate)
      (PMMA), poly(4-vinyl pyridine) (P4VP), and (3-aminopropyl)triethoxysilane
      (APTES). An optical microscope with a heating/cooling stage was employed to
      measure the induction time of heterogeneous nucleation. The surface topography
      and roughness were characterized by atomic force microscopy. Contact angles for
      crystallization solution on the investigated surfaces were measured by a contact
      angle meter. From the theoretical analysis, the energetic barrier to
      heterogeneous nucleation was found to increase at higher contact angles and to
      decrease at higher roughness. Experimentally, a qualitative increase of the
      induction time of the heterogeneous nucleation on P2HEMA, APTES, and PMMA
      surfaces with the contact angle was observed. Such surfaces as P2HEMA, PLG, and
      APTES, which were of higher roughness, were shown to promote the heterogeneous
      nucleation. In addition, the surface with specific topography is expected to
      increase the possibility of the formation of a critical nucleus. Finally, the
      P4VP surface appeared to suppress the heterogeneous nucleation as a result of the
      electrostatic interaction between the lysozyme and P4VP molecules.

PMID- 18044863
TI  - Passive water-lipid peptide translocators with conformational switches: from
      single-molecule probe to cellular assay.
AB  - Peptide design for unassisted passive water-lipid translocation remains a
      challenge, notwithstanding its importance for drug delivery. We introduce a
      design paradigm based on conformational switches operating as passive
      translocation vehicles. The interfacial behavior of the molecular prototype,
      probed in single-molecule AFM experiments, reveals a near-barrierless
      translocation. The associated free-energy agrees with mesoscopic measurements,
      and the in vitro behavior is quantitatively reproduced in cellular assays. The
      prototypes herald the advent of novel nanobiomaterials for passive translocation.

PMID- 18044864
TI  - Adsorption of water in finite length carbon slit pore: comparison between
      computer simulation and experiment.
AB  - The effects of surface dimensions and topology on the adsorption of water on a
      graphite surface at 298 K were investigated using the grand canonical Monte Carlo
      (GCMC) simulation. Regarding the surface topology, we specifically considered the
      functional group and its position on the surface. The hydroxyl group (OH) is used
      as a model for the functional group. For describing the interaction of water, we
      used the potential model proposed by Muller et al., and the simulated isotherms
      of water in slit pores are found to depend on the position and concentration of
      the functional group. The onset of adsorption shifts to lower pressure when the
      concentration of functional group increases or when the functional group is
      positioned at the center of the graphene surface. The configuration of a group of
      functional groups also affects the adsorption isotherm. In all cases
      investigated, we have found that the hysteresis loop always exists, and the loop
      size depends on the concentration of the functional group and its position.
      Finally, we tested the molecular model of water adsorption on a functional
      graphite pore against the experimental data of a commercial activated carbon. The
      agreement is found to be satisfactory when the model porous solid is composed of
      pores having width in the range between 10 and 20 A and functional groups
      positioned at the center of the graphitic wall.

PMID- 18044865
TI  - Free volume in C60 modified PPO polymer membranes by positron annihilation
      lifetime spectroscopy.
AB  - PPO (poly(2,6-dimethyl-1,4-phenylene oxide)) is a well-known membrane material
      showing good gas separation properties. The incorporation of nanoparticles can
      enhance or deteriorate the performance of composite membranes, sometimes
      depending only on the way of the composite preparation. We have modified the PPO
      polymer with C60 fullerenes up to a content of 2 wt %. Previous investigations
      showed a strong dependence of permeability on whether the C60 is simply dispersed
      in the polymer or chemically bonded to the polymer chains. Free volume effects
      were suggested as an explanation but not experimentally confirmed. Here, we
      present free volume studies by positron annihilation lifetime spectroscopy. An
      additional long positron lifetime shows the increased free volume of composite
      samples, while the high electron affinity of C60 helps to indicate the
      homogeneity of the samples. Combining the presented results with permeability
      measurements refines the understanding of this promising membrane material.

PMID- 18044867
TI  - Revealing the way of self-complementary dimerization for a shape-persistent
      macrocycle using density functional theory calculations.
AB  - A preferred geometry of a planar shape-persistent dimeric macrocycle with
      diacetylene-linked alternating hexylbenzene and perfluorobenzene rings is
      revealed by resolving its three-dimensional spatial energy profile using density
      functional theory calculations. The resulting dimer exhibits a face-to-face
      geometry with about 51.5 degrees rotational off-set around the principal axis and
      an intermolecular distance of about 3.91 A. The calculated intermolecular
      interaction energy and the 1H NMR chemical shifts of the exo- and endo-annular
      protons of the predicted dimer agree very well with the recent experimental data.
      More importantly, the current study resolves the ambiguity observed in the
      experiment pertaining to how the dimer would form, and provides insight for
      predicting the geometry of similar dimeric macrocycles or other pi-pi interacting
      systems.

PMID- 18044866
TI  - Reversible stiffening transition in beta-hairpin hydrogels induced by ion
      complexation.
AB  - We have previously shown that properly designed lysine and valine-rich peptides
      undergo a random coil to beta-hairpin transition followed by intermolecular self
      assembly into a fibrillar hydrogel network only after the peptide solutions are
      heated above the intramolecular folding transition temperature. Here we report
      that these hydrogels also undergo a stiffening transition as they are cooled
      below a critical temperature only when boric acid is used to buffer the peptide
      solution. This stiffening transition is characterized by rheology, dynamic light
      scattering, and small angle neutron scattering. Rheological measurements show
      that the stiffening transition causes an increase in the hydrogel storage modulus
      (G') by as much as 1 order of magnitude and is completely reversible on
      subsequently raising the temperature. Although this reversible transition
      exhibits rheological properties that are similar to polyol/borax solutions, the
      underlying mechanism does not involve hydroxyl-borate complexation. The
      stiffening transition is mainly caused by the interactions between lysine and
      boric acid/borate anion and is not driven by the changes in the secondary
      structure of the beta-hairpin peptide. Addition of glucose to boric acid and
      peptide solution disrupts the stiffening transition due to competitive glucose
      borate complexation.

PMID- 18044869
TI  - Vibrational energy relaxation of the bend fundamental of dilute water in liquid
      chloroform and d-chloroform.
AB  - The population lifetimes of the bend fundamental of dilute water in liquid
      chloroform (8.5 ps) and d-chloroform (28.5 ps) display an interesting solvent
      isotope effect. As the lowest excited vibrational state of the molecule, the
      water bend fundamental relaxes directly to the ground state with about 1600 cm-1
      of energy released to the other degrees of freedom. The strong solvent isotope
      effect along with the large energy gap indicates the participation of solvent
      vibrational modes in this vibrational energy relaxation process. We calculate the
      vibrational energy relaxation rates of the water bend in chloroform and d
      chloroform using the Landau-Teller formula with a new potential model developed
      and parametrized self-consistently to describe the chloroform-water interaction.
      The computed values are in reasonable agreement with the experimental results,
      and the trend for the isotope effect is correct. It is found that energy transfer
      to the solvent vibrations does indeed play an important role. Nevertheless, no
      single dominant solvent accepting mode can be identified; the relaxation appears
      to involve both the bend and the C-Cl stretches, and frequency changes of all of
      these modes upon deuteration contribute to the observed solvent isotope effect.

PMID- 18044868
TI  - Electronic excitations of green fluorescent proteins: modeling solvatochromatic
      shifts of red fluorescent protein chromophore model compound in aqueous
      solutions.
AB  - While green fluorescent proteins (GFPs) have been widely used as tools in
      biochemistry, cell biology, and molecular genetics, novel red fluorescent
      proteins (RFPs) with red fluorescence emission have also been identified, as
      complements to the existing GFP technology. The unusual spectrophotometric and
      fluorescence properties of GFPs and RFPs are controlled by the protonation states
      and possibly cis/trans isomerization within their chromophores. In this work, we
      have investigated the electronic structures, liquid structures, and solvent
      shifts of the possible neutral and anionic protonated states and the cis/trans
      isomerization of a RFP chromophore model compound HBMPI in aqueous solutions. The
      calculations reproduced the experimental absorption solvatochromatic shifts of
      dilute HBMPI in water under neutral and anionic conditions. Unlike the GFP
      chromophore, the RFP chromophore model compound HBMPI in basic solution can only
      adopt a conformation where the C=C bond between the bridge group and the
      imidazolinone ring and the C-C bond between the imidazolinone and ethylene groups
      exist in cis and trans conformations, respectively. Moreover, the solvent-solute
      hydrogen-bonding interactions are found to contribute significantly to the total
      solvent shifts of pi-pi* excitations of aqueous HBMPI solutions, signifying the
      importance of protein environment in the determination of the conformation of the
      chromophores in red fluorescent proteins.

PMID- 18044870
TI  - Enthalpy-entropy compensation: a phantom or something useful?
AB  - In various chemical systems enthalpy-entropy compensation (EEC) is a well-known
      rule of behavior, although the physical roots of it are still not completely
      understood. It has been frequently questioned whether EEC is a truly physical
      phenomenon or a coincidence due to trivial mathematical connections between
      statistical-mechanical parameters or even simpler, a phantom effect resulting
      from the misinterpretation of experimental data. Here, we review EEC from a new
      standpoint and conclude that it may be rationalized in terms of hidden but
      physically real factors implying a Carnot-cycle model in which a micro-phase
      transition (MPT) plays a crucial role. Examples of such MPTs underlying
      physically valid EEC should be typically cooperative processes in supramolecular
      aggregates, like changes of structured water at hydrophobic surfaces,
      conformational transitions upon ligand-biopolymer binding, and so forth. The MPT
      notion could help rationalize the occurrence of EEC in connection with hydration
      and folding of proteins, functioning of molecular motors, and similar phenomena.

PMID- 18044872
TI  - A novel composite: layered double hydroxides encapsulated in vesicles.
AB  - We report a novel composite: layered double hydroxides (LDHs) encapsulated in
      vesicles. It was found that positively charged Mg3Al-LDH nanoparticles can induce
      the spontaneous formation of vesicles in a mixture of a zwitterionic surfactant,
      dodecyl betaine (C12BE), and an anionic surfactant, sodium bis(2-ethylhexyl)
      sulfosuccinate (AOT), and importantly, we obtain simultaneously a novel composite
      of Mg3Al-LDH encapsulated in vesicles. The obtained composite is very stable and
      expected to be potentially used in drug delivery and gene therapy.

PMID- 18044871
TI  - Evaluation of enzymatic activity on nanoscale polystyrene-block
      polymethylmethacrylate diblock copolymer domains.
AB  - Understanding structural and functional changes of polymeric surface-bound
      proteins is extremely important as polymers play an increasingly significant role
      as arrays and substrates in proteomics applications. We carried out, for the
      first time, quantitative activity measurements of horseradish peroxidase (HRP)
      enzymes immobilized selectively on the polystyrene domains of microphase
      separated polystyrene-block-polymethylmethacrylate ultrathin films. The specific
      enzymatic activity of HRP adsorbed on the diblock copolymer surface was evaluated
      and compared to that of HRP in free solution. We demonstrate that the polymeric
      surface-bound HRP molecules maintain approximately 85% of their activity in free
      solution. The unique advantages of diblock copolymer templates, involving
      nanoscale self-assembly and largely retained protein functionality, make the
      spontaneously constructed enzyme nanoarrays highly suitable as proteomics
      substrates. Our novel assembly method of providing functional enzymes on diblock
      copolymer thin films can be greatly beneficial for high-throughput and high
      density protein assays.

PMID- 18044873
TI  - Correlation of the vibrations of the aqueous azide ion with the O-H modes of
      bound water molecules.
AB  - Dual frequency two-dimensional infrared spectroscopy (2D-IR) has been used to
      investigate the dynamics of the azide-water solvation shell. The memory of the
      azide transition frequencies is detected in the echo emitted by the OH stretching
      mode of the ion-bound water molecules. There is a significant positive
      correlation of the two frequency distributions that decays on a 140 fs time
      scale. The result confirms that the O-H bond of water molecules in the solvent
      shell have frequency fluctuations that are considerably slowed from those that
      are known in bulk water. The positive correlation is attributed to cooperative
      interactions of coordinated water molecules with an azide ion.

PMID- 18044874
TI  - Mixed valence compounds as probes to determine the polarity of 1-butyl-3
      methylimadazolium ionic liquids.
AB  - Radical cations and dications of three bishydrazines belonging to the Class II
      mixed valence compounds have been generated, either spontaneously or by oxidation
      with AgSbF6, in two 1-butyl-3-methylimidazolium (4+) ionic liquids having BF4(-)
      and PF6(-) as counterions. The optical spectra of these intermediates have
      allowed evaluation of Marcus' reorganization energy lambda(s), a parameter that
      is directly proportional to the solvent polarity. Remarkable differences in
      lambda(s), as large as 600 cm(-1), have been observed as a function of the
      counterion, with these data providing support for the observed differences
      between both ionic liquids (4(+)BF4(-) and 4(+)PF6(-)) in catalysis. However, in
      terms of polarity, the lambda(s) values rank the hydrophilic 4(+)BF4(-) as being
      similar to dimethyl sulfoxide and dimethylformamide, while the polarity of
      hydrophobic 4(+)PF6(-) is analogous to acetonitrile. Overall, our results
      indicate that ionic liquids are not exceptional liquids in terms of polarity.

PMID- 18044875
TI  - Magnetic alignment study of rare-earth-containing liquid crystals.
AB  - The liquid-crystalline rare-earth complexes of the type [Ln(LH)3(DOS)3]-where Ln
      is Tb, Dy, Ho, Er, Tm, or Yb; LH is the Schiff base N-octadecyl-4
      tetradecyloxysalicylaldimine; and DOS is dodecylsulfate-exhibit a smectic A
      phase. Because of the presence of rare-earth ions with a large magnetic
      anisotropy, the smectic A phase of these liquid crystals can be easier aligned in
      an external magnetic field than smectic A phases of conventional liquid crystals.
      The magnetic anisotropy of the [Ln(LH)3(DOS)3] complexes was determined by
      measurement of the temperature-dependence of the magnetic susceptibility using a
      Faraday balance. The highest value for the magnetic anisotropy was found for the
      dysprosium(III) complex. The magnetic alignment of these liquid crystals was
      studied by time-resolved synchrotron small-angle X-ray scattering experiments.
      Depending on the sign of the magnetic anisotropy, the director of the liquid
      crystalline molecules was aligned parallel or perpendicular to the magnetic field
      lines. A positive value of the magnetic anisotropy (and parallel alignment) was
      found for the thulium(III) and the ytterbium(III) complexes, whereas a negative
      value of the magnetic anisotropy (and perpendicular alignment) was observed for
      the terbium(III) and dysprosium(III) complexes.

PMID- 18044876
TI  - The catalytic activity of proline racemase: a quantum mechanical/molecular
      mechanical study.
AB  - The enzyme proline racemase from the eukaryotic parasite Trypanosoma cruzi
      (responsible for endemic Chagas disease) catalyzes the reversible stereoinversion
      of chiral Calpha in proline. We employed a new combined quantum mechanical and
      molecular mechanical (QM/MM) potential to study the reaction mechanism of the
      enzyme. Three critical points were found: two almost isoenergetic minima (M1a and
      M2a), in which the enzyme is bound to L- and D-Pro, respectively, and a
      transition state (TSCa), unveiling a highly asynchronous concerted process. A
      systematic analysis was performed on the optimized geometries to point out the
      key role played by some residues in stabilizing the transition state.

PMID- 18044877
TI  - New insights into the visible-light-induced DNA cleavage activity of
      dipyridoquinoxaline complexes of bivalent 3d-metal ions.
AB  - Dipyridoquinoxaline (dpq) complexes of bivalent 3d-metal ions, viz.,
      [FeII(dpq)3](PF6)2 (1), [CoII(dpq)3](ClO4)2 (2), [NiII(dpq)3](ClO4)2 (3),
      [CuII(dpq)2(H2O)](ClO4)2 (4), [ZnII(dpq)3](ClO4)2 (5), and
      [ZnII(dpq)2(DMF)2](ClO4)2 (5a) (DMF = N,N-dimethylformamide), are prepared and
      their photoinduced DNA cleavage activity studied. Structural characterization for
      the complexes 1 and 5a is done by single-crystal X-ray crystallography. All the
      complexes show efficient binding propensity to calf thymus DNA with a binding
      constant (K) value of approximately 10(5) M(-1). Complexes 1, 2, and 4 show metal
      based cyclic voltammetric responses at 1.2, 0.4, and 0.09 V (vs SCE) in DMF 0.1 M
      [Bun4N](ClO4) assignable to the respective FeIII/FeII, CoIII/CoII, and CuII/CuI
      couples. The NiII and ZnII complexes do not show any metal-based redox process.
      The dpq-based reductions are observed in the potential range of -1.0 to -1.7 V vs
      SCE. DNA melting and viscosity data indicate the groove-binding nature of the
      complexes. Control experiments using distamycin-A suggest a minor groove-binding
      propensity of the complexes. The complexes exhibit photoinduced cleavage of
      supercoiled pUC19 DNA in UV light of 365 nm. The diamagnetic d6-FeII and d10-ZnII
      complexes are cleavage-inactive on irradiation with visible light. The
      paramagnetic d7-CoII and d9-CuII complexes exhibit efficient DNA cleavage
      activity on photoirradiation at their respective d-d band. The paramagnetic d8
      NiII complex displays only minor DNA cleavage activity on irradiation at its d-d
      band. The DNA cleavage reactions at visible light under aerobic conditions
      involve the formation of hydroxyl radical. The CoII complex shows photocleavage
      of DNA under an argon atmosphere. Theoretical calculations on the complexes
      suggest a photoredox pathway in preference to a type-2 process forming singlet
      oxygen for the visible-light-induced DNA cleavage activity of the 3d-metal
      complexes. The theoretical data also predict that the photoredox pathway is
      favorable for the 3d7-CoII and 3d9-CuII complexes to exhibit DNA cleavage
      activity, while the analogous 3d6-FeII and 3d8-NiII complexes are energetically
      unfavorable for the exhibition of such activity under visible light. The CoII and
      CuII complexes are better suited for designing and developing new metal-based PDT
      agents than their cleavage-inactive FeII, NiII, and ZnII analogues.

PMID- 18044878
TI  - Rates of proton transfer to Fe-S-based clusters: comparison of clusters
      containing {MFe(mu(2)-S)(2)}n+ and {MFe(3)(mu(3)-S)(4)}n+ (M = Fe, Mo, or W)
      cores.
AB  - The rates of proton transfer from [pyrH]+ (pyr = pyrrolidine) to the binuclear
      complexes [Fe2S2Cl4]2- and [S2MS2FeCl2]2- (M = Mo or W) are reported. The
      reactions were studied using stopped-flow spectrophotometry, and the rate
      constants for proton transfer were determined from analysis of the kinetics of
      the substitution reactions of these clusters with the nucleophiles Br- or PhS- in
      the presence of [pyrH]+. In general, Br- is a poor nucleophile for these
      clusters, and proton transfer occurs before Br- binds, allowing direct measure of
      the rate of proton transfer from [pyrH]+ to the cluster. In contrast, PhS- is a
      better nucleophile, and a pathway in which PhS- binds preferentially to the
      cluster prior to proton transfer from [pyrH]+ usually operates. For the reaction
      of [Fe2S2Cl4]2- with PhS- in the presence of [pyrH]+ both pathways are observed.
      Comparison of the results presented in this paper with analogous studies reported
      earlier on cuboidal Fe-S-based clusters allows discussion of the factors which
      affect the rates of proton transfer in synthetic clusters including the
      nuclearity of the cluster core, the metal composition, and the nature of the
      terminal ligands. The possible relevance of these findings to the protonation
      sites of natural Fe-S-based clusters, including FeMo-cofactor from nitrogenase,
      are presented.

PMID- 18044879
TI  - Magnetic circular dichroism evidence for a weakly coupled heme-radical pair at
      the active site of cytochrome cd1, a nitrite reductase.
AB  - In nitrite-treated cytochrome cd1 nitrite reductase, heme d1 is electron
      paramagnetic resonance silent but paramagnetic. Analysis of the unusual
      temperature dependence of the magnetic circular dichroism spectra unambiguously
      demonstrates that the heme d1 is not in the oxoferryl (FeIV=O) state but is low
      spin FeIII weakly coupled to a radical species. This species could be either a
      protein-bound radical generated by a nitrite ion reacting with a heme group
      resulting in a one-electron oxidation of an amino acid residue, possibly tyrosine
      or tryptophan, adjacent to heme d1, or a heme d1 FeIIINO complex.

PMID- 18044880
TI  - fac-[Re(CO)(3)L](+) complexes with N-CH(2)-CH(2)-X-CH(2)-CH(2)-N tridentate
      ligands. synthetic, X-ray crystallographic, and NMR spectroscopic investigations.
AB  - Polyamine ligands (L) have excellent binding characteristics for the formation of
      fac-99mTc(CO)3-based radiopharmaceuticals. Normally, these L are elaborated so as
      to leave pendant groups designed to impart useful biodistribution characteristics
      to the fac-[99mTc(CO)3L] imaging agent. Our goal is to lay a foundation for
      understanding the features of the bound elaborated ligands by using the fac
      [Re(CO)3L]-analogue approach with the minimal prototypical ligands,
      diethylenetriamine (dien) or simple dien-related derivatives. Treatment of the
      fac-[Re(CO)3(H2O)3]+ cation with such triamine (NNN) ligands afforded fac
      [Re(CO)3L]+ complexes. Ligand variations included having a central amine
      thioether donor, thus allowing X-ray crystallographic and NMR spectroscopic
      comparisons of fac-[Re(CO)3L]+ complexes with NNN and NSN ligands. fac
      [Re(CO)3L]+ complexes with two terminal exo-NH groups exhibit unusually far
      upfield exo-NH NMR signals in DMSO-d6. Upon the addition of Cl-, these exo-NH
      signals move downfield, while the signals of any endo-NH or central NH groups
      move very little. This behavior is attributed to the formation of 1:1 ion pairs
      having selective Cl- hydrogen bonding to both exo-NH groups. Base addition to a
      DMSO-d6 solution of meso-exo-[Re(CO)3(N,N',N''-Me3dien)]PF6 led to isomerization
      of only one NHMe group, producing the chiral isomer. The meso isomer did not
      form. The [Re(CO)3(N,N,N',N'',N''
      pentamethyldiethylenetriamine)]triflate.[Re(CO)3(mu3-OH)]4.3.35H2O crystal, the
      first structure with a fac-[Re(CO)3L] complex cocrystallized with this well-known
      cluster, provided parameters for a bulky NNN ligand and also reveals CO-CO
      interlocking intermolecular interactions that could stabilize the crystal.

PMID- 18044881
TI  - Determination of the intrinsic affinities of multiple site-specific Mg(2+) ions
      coordinated to domain 6 of a group II intron ribozyme.
AB  - Group II introns are large metallo-ribozymes that use divalent metal ions in
      folding and catalysis. The 3'-terminal domain 6 (D6) contains a conserved
      adenosine whose 2'-OH group acts as the nucleophile in the first splicing step.
      In the hierarchy of folding, D6 binds last into the active site. In order to
      investigate and understand the folding process to the catalytically active intron
      structure, it is important to know the individual binding affinities of Mg2+ ions
      to D6. We recently studied the solution structure of a 27 nucleotide long D6 (D6
      27) from the mitochondrial yeast group II intron Sc.ai5gamma, also identifying
      five Mg2+ binding sites including the one at the 5'-terminal phosphate residues.
      Mg2+ coordination to the 5'-terminal di- and triphosphate groups is strongest
      (e.g., log KA,TP = 4.55 +/- 0.10) and is evaluated here in detail for the first
      time. The other four binding sites within D6-27 are filled simultaneously (e.g.,
      log KA,BR = 2.38 +/- 0.06) and thus compete for the free Mg2+ ions in solution,
      having a distinct influence on the individual affinities of the various sites.
      For the first time, we take this competition into account to obtain the intrinsic
      binding constants, describing a method that is generally applicable. Our data
      illustrates that any RNA molecule undergoing tertiary contacts to a second RNA
      molecule first needs to be loaded evenly and specifically with metal ions to
      compensate for the repulsion between the negatively charged RNA molecules.

PMID- 18044882
TI  - Kinetics of dissociation of molecular oxygen from a superoxorhodium(III) complex
      and reactivity of a macrocyclic rhodium(II) ion.
AB  - The kinetics of disappearance of the superoxorhodium complex L2(H2O)RhOO2+ (L2 =
      meso-hexamethylcyclam) were determined in the presence of several oxidants (H2O2,
      (NH3)5CoBr2+, and IrCl62-) in both air-free and air-saturated aqueous solutions.
      Under air-free conditions, the reaction obeyed first-order kinetics. After the
      correction for the appropriate stoichiometric factors, the value of the rate
      constant kh was the same irrespective of the oxidant, kh = 2.18 (+/-0.37) x 10(
      4) s(-1) at 25.0 degrees C in acidic solutions. The disappearance of
      L2(H2O)RhOO2+ was slower in the presence of O2. All the data suggest a sequence
      of reactions beginning with homolytic dissociation of O2 from L2(H2O)RhOO2+,
      followed by capture of the newly generated L2(H2O)Rh2+ by added oxidants in
      competition with O2. The equilibrium constant for O2 binding by L2(H2O)Rh2+ is
      109-fold greater than that for the cobalt analogue. This difference is attributed
      to the lower reduction potential of the rhodium complex.

PMID- 18044883
TI  - Speciation of uranyl complexes in ionic liquids by optical spectroscopy.
AB  - Uranyl complexes dissolved in room-temperature ionic liquids have diagnostic
      absorption and emission spectra which reflect the molecular symmetry and
      geometry. In particular, the characteristic vibrational fine structure of the
      absorption spectra allows identification of the molecular symmetry of a uranyl
      complex. The concept of speciation of uranyl complexes is illustrated for the
      hydrated uranyl ion, the tetrachloro complex [UO2Cl4]2-, the trinitrato complex
      [UO2(NO3)3]-, the triacetato complex [UO2(CH3COO)3]-, and the crown ether complex
      [UO2(18-crown-6)]2+ in imidazolium and pyrrolidinium
      bis(trifluoromethylsulfonyl)imide ionic liquids. The competition between 18-crown
      6 and small inorganic ligands for coordination to the uranyl ion was
      investigated. The crystal structures of the hydrolysis product [(UO2)2(mu2
      OH)2(H2O)6] [UO2Br4](18-crown-6)4 and imidazolium salt [C6mim]2[UO2Br4] are
      described.

PMID- 18044884
TI  - Reactivity and catalytic activity of a robust ruthenium(II)-triphos complex.
AB  - The ruthenium(II)-triphos acetato complex [RuCl(OAc)(kappa3-triphos)] (triphos =
      (PPh2CH2)3CMe) has been found to be an active catalyst precursor for the
      hydrogenation of 1-alkenes under relatively mild conditions (5-50 bar H2, 50
      degrees C). In contrast to related triphenylphosphine complexes,
      [RuCl(OAc)(kappa3-triphos)] is much less air sensitive and high catalytic
      activities were achieved when catalyst samples were prepared without exclusion of
      air or moisture. Substitution of the acetato ligand can be effected by treatment
      of acid, affording [Ru2(mu-Cl)3(kappa3-triphos)2]Cl and [RuCl(kappa3
      triphos)]2(BF4)2 with aqueous HCl and [Et2OH]BF4, respectively, or by heating
      with dmpm in the presence of [NH4]PF6, resulting in formation of [RuCl(kappa2
      dmpm)(kappa3-triphos)]PF6 (dmpm = PMe2CH2PMe2). A hydride complex, [RuHCl(kappa3
      triphos)], formed by acetato-mediated heterolytic cleavage of dihydrogen is
      proposed as the active catalytic species. An inner-sphere, monohydride mechanism
      is suggested for the catalytic cycle, with chloro and triphos ligands playing a
      spectator role. These mechanistic proposals are consistent with reactivity
      studies carried out on [RuCl(OAc)(kappa3-triphos)] and [RuH(OAc)(kappa3-triphos)]
      and supported by a computational analysis. The solid-state structures of
      [RuCl(OAc)(kappa3-triphos)], [RuCl(kappa3-triphos)]2(BF4)2, and [RuCl(kappa2
      dmpm)(kappa3-triphos)]PF6 have been established by X-ray diffraction.

PMID- 18044885
TI  - Development of a series of P(CH(2)N=CHR)(3) and trisubstituted 1,3,5-Triaza-7
      phosphaadamantane ligands.
AB  - The synthesis and structure of a series of novel phosphine ligands derived from
      the condensation of P(CH2NH2) with aldehydes are described. Depending on the
      reaction conditions, either substituted tris(iminomethyl)phosphine, P(CH2N=CHR)3,
      or 1,3,5-triaza-7-phosphaadamantane structures substituted at the "lower rim",
      PTAR3, are obtained.

PMID- 18044886
TI  - Substituent effects in formally quintuple-bonded ArCrCrAr compounds (Ar =
      terphenyl) and related species.
AB  - The effects of different terphenyl ligand substituents on the quintuple Cr-Cr
      bonding in arylchromium(I) dimers stabilized by bulky terphenyl ligands (Ar) were
      investigated. A series of complexes, ArCrCrAr (1-4; Ar = C6H2-2,6-(C6H3-2,6
      iPr2)2-4-X, where X = H, SiMe3, OMe, and F), was synthesized and structurally
      characterized. Their X-ray crystal structures display similar trans-bent
      C(ipso)CrCrC(ipso) cores with short Cr-Cr distances that range from 1.8077(7) to
      1.8351(4) A. There also weaker Cr-C interactions [2.294(1)-2.322(2) A] involving
      an C(ipso) of one of the flanking aryl rings. The data show that the changes
      induced in the Cr-Cr bond length by the different substituents X in the para
      positions of the central aryl ring of the terphenyl ligand are probably a result
      of packing rather than electronic effects. This is in agreement with density
      functional theory (DFT) calculations, which predict that the model compounds (4
      XC6H4)CrCr(C6H4-4-X) (X = H, SiMe3, OMe, and F) have similar geometries in the
      gas phase. Magnetic measurements in the temperature range of 2-300 K revealed
      temperature-independent paramagnetism in 1-4. UV-visible and NMR spectroscopic
      data indicated that the metal-metal-bonded solid-state structures of 1-4 are
      retained in solution. Reduction of (4-F3CAr')CrCl (4-F3CAr' = C6H2-2,6-(C6H3-2,6
      iPr2)2-4-CF3) with KC8 gave non-Cr-Cr-bonded fluorine-bridged dimer {(4
      F3CAr')Cr(mu-F)(THF)}2 (5) as a result of activation of the CF3 moiety. The
      monomeric, two-coordinate complexes [(3,5-iPr2Ar*)Cr(L)] (6, L = THF; 7, L =
      PMe3; 3,5-iPr2Ar* = C6H1-2,6-(C6H-2,4,6-iPr3)2-3,5-iPr2) were obtained with use
      of the larger 3,5-Pri2-Ar* ligand, which prevents Cr-Cr bond formation. Their
      structures contain almost linearly coordinated CrI atoms, with high-spin 3d5
      configurations. The addition of toluene to a mixture of (3,5-iPr2Ar*)CrCl and KC8
      gave the unusual dinuclear benzyl complex [(3,5-iPr2Ar*)Cr(eta3:eta6-CH2Ph)Cr(Ar*
      1-H-3,5-iPr2)] (8), in which a C-H bond from a toluene methyl group was
      activated. The electronic structures of 5-8 have been analyzed with the aid of
      DFT calculations.

PMID- 18044887
TI  - Secondary nucleation and growth of ZnO.
AB  - Recently we discovered that under certain conditions new crystal growth (branch)
      can be induced on specific crystalline planes of the same material. This is a new
      phenomenon and is in sharp contrast to typical nucleation and growth in which a
      crystal will simply grow larger in preferred directions depending on the surface
      energy of the specific crystalline planes. Based on our observation, we developed
      a sequential nucleation and growth technique offering the power to assemble
      complex hierarchical crystals step-by-step. However, the key questions of when
      and how the secondary nucleation takes place have not been answered. Here we
      systematically study secondary ZnO crystal growth using organic diamine additives
      with a range of chain lengths and concentration. We found that ZnO branches form
      for a narrow diamine concentration range with a critical lower and upper critical
      nucleation concentration limit, which increases by about a factor of 5 for each
      additional carbon in the diaminoalkane chain. Our results suggest that the narrow
      window for secondary growth is dictated by the solubility of the ZnO crystals,
      where the low critical nucleation concentration is determined by slight etching
      of the surface to produce new nucleation sites, and the upper critical
      concentration is determined by the supersaturation concentration. Kinetic
      measurements show that the induction time and growth rate increase with
      increasing diamine concentration and follow classical nucleation and growth
      theory. Observations of branch morphological evolution reveal the mechanisms
      guiding the tunable crystal size and morphology.

PMID- 18044888
TI  - Residue-specific pKa determination of lysine and arginine side chains by indirect
      15N and 13C NMR spectroscopy: application to apo calmodulin.
AB  - Electrostatic interactions in proteins can be probed experimentally through
      determination of residue-specific acidity constants. We describe here triple
      resonance NMR techniques for direct determination of lysine and arginine side
      chain protonation states in proteins. The experiments are based on detection of
      nonexchangeable protons over the full range of pH and temperature and therefore
      are well suited for pKa determination of individual amino acid side chains. The
      experiments follow the side-chain 15Nzeta (lysine) and 15Nepsilon or 13Czeta
      (arginine) chemical shift, which changes due to sizable changes in the
      heteronuclear electron distribution upon (de)protonation. Since heteronuclear
      chemical shifts are overwhelmed by the charge state of the amino acid side chain
      itself, these methods supersede 1H-based NMR in terms of accuracy, sensitivity,
      and selectivity. Moreover, the 15Nzeta and 15Nepsilon nuclei may be used to probe
      changes in the local electrostatic environment. Applications to three proteins
      are described: apo calmodulin, calbindin D9k, and FKBP12. For apo calmodulin,
      residue-specific pKa values of lysine side chains were determined to fall between
      10.7 and 11.2 as a result of the high net negative charge on the protein surface.
      Ideal two-state titration behavior observed for all lysines indicates the absence
      of significant direct charge interactions between the basic residues. These
      results are compared with earlier studies based on chemical modification.

PMID- 18044890
TI  - Watching electrons move in real time: ultrafast infrared spectroscopy of a
      polymer blend photovoltaic material.
AB  - The dynamics of photoinduced charge separation and the motion of the resulting
      electrons are examined in an organic photovoltaic material with a combination of
      ultrafast two-dimensional infrared (2D IR) and visible pump-infrared probe (Vis
      IR) spectroscopy. The carbonyl (C=O) stretch of the butyric acid methyl ester
      group of a functionalized fullerene, PCBM, is probed as a local vibrational
      reporter of the dynamics in a blend of the fullerene with a conjugated polymer,
      CN-MEH-PPV. Charge transfer occurs preferentially at the interfaces between the
      roughly spherical domains of fullerene molecules and the polymer. Comparison of
      the Vis-IR and 2D IR spectra reveals that the fullerene molecules at the
      interfaces of the domains possess higher frequency carbonyl vibrational modes,
      while molecules in the centers of the domains have lower frequency modes relative
      to the center of the transition. The correlation between the frequency of a
      carbonyl mode and the spatial position of its host fullerene molecule provides a
      means to observe the motion of electrons within individual domains through the
      spectral evolution of the carbonyl bleach. From the spectral evolution, we find
      that the average radial velocity of electrons is 1-2 m/s, which suggests an
      intrinsic mobility that is at least one order of magnitude greater than the
      mobility in the polymer blend. The results indicate that organic solar cells with
      higher mobility and thus efficiency may be realized by controlling the morphology
      of the polymer and fullerene materials.

PMID- 18044889
TI  - Sphingomyelin/phosphatidylcholine and cholesterol interactions studied by imaging
      mass spectrometry.
AB  - Label-free imaging mass spectrometry is utilized the first time to study lipid
      lipid interactions in a model membrane system. Ternary lipid mixtures of
      cholesterol (CH), sphingomyelin (SM), and phosphatidylcholine (PC) on supported
      Langmuir-Blodgett films are investigated as a mimic of the cellular membrane. The
      unique chemical specificity and imaging capability allow identification and
      localization of each lipid molecule in the membranes. The SM and PC in each
      ternary mixture vary in their acyl chain saturation with both, either, or neither
      one double bonded at the same position of their acyl chain. For the ternary
      mixtures with SM and PC both saturated or unsaturated, all the lipids are evenly
      distributed in the molecule-specific images. However, domain structures were
      observed for the two mixtures with either SM or PC unsaturated. In both films,
      the saturated lipid, whether it is SM or PC, colocalized with CH while the
      unsaturated lipid was excluded from the CH domains. These results strongly
      suggest that acyl chain saturation, rather than the specific interactions between
      SM and CH, is the dominating factor for SM colocalization with CH in the raft
      areas of the cellular membranes.

PMID- 18044891
TI  - Chemosensory performance of molecularly imprinted fluorescent conjugated polymer
      materials.
AB  - Fluorescent conjugated polymers are an attractive basis for the design of low
      detection limit sensing devices owing to their intrinsic signal amplification
      capability. A simple and universal method to rationally control or fine-tune the
      chemodetection selectivity of conjugated polymer materials toward a desired
      analytical target would further benefit their applications. In a quest of such a
      method we investigated a general approach to cross-linked molecularly imprinted
      fluorescent conjugated polymer (MICP) materials that possess an intrinsic
      capability for signal transduction and have potential to enhance selectivity and
      sensitivity of sensor devices based on conjugated polymers. To study these
      capabilities, we prepared an MICP material for the detection of 2,4,6
      trinitrotoluene and related nitroaromatic compounds. We found the imprinting
      effect in this material to be based on analyte shape/size recognition being
      substantial and generally overcoming other competing thermodynamically determined
      trends. The described molecularly imprinted fluorescent conjugated polymers show
      remarkable air stability and photostability, high fluorescence quantum yield, and
      reversible analyte binding and therefore are advantageous for sensing
      applications due to the ability to "preprogram" their detection selectivity
      through a choice of an imprinted template.

PMID- 18044892
TI  - Highly soluble [1]benzothieno[3,2-b]benzothiophene (BTBT) derivatives for high
      performance, solution-processed organic field-effect transistors.
AB  - 2,7-Dialkyl[1]benzothieno[3,2-b]benzothiophenes were tested as solution
      processible molecular semiconductors. Thin films of the organic semiconductors
      deposited on Si/SiO2 substrates by spin coating have well-ordered structures as
      confirmed by XRD analysis. Evaluations of the devices under ambient conditions
      showed typical p-channel FET responses with the field-effect mobility higher than
      1.0 cm2 V-1 s-1 and Ion/Ioff of approximately 10(7).

PMID- 18044893
TI  - Single crystal-to-single crystal transformation from ferromagnetic discrete
      molecules to a spin-canting antiferromagnetic layer.
AB  - A unique single crystal-to-single crystal transformation from 0D discrete
      molecules to a 2D coordination polymer exhibits magnetic property changes from a
      short-range ferromagnetic coupling to a long-range canting antiferromagnetic
      ordering.

PMID- 18044894
TI  - Single-label kinase and phosphatase assays for tyrosine phosphorylation using
      nanosecond time-resolved fluorescence detection.
AB  - The collision-induced fluorescence quenching of a 2,3-diazabicyclo[2.2.2]oct-2
      ene-labeled asparagine (Dbo) by hydrogen atom abstraction from the tyrosine
      residue in peptide substrates was introduced as a single-labeling strategy to
      assay the activity of tyrosine kinases and phosphatases. The assays were tested
      for 12 different combinations of Dbo-labeled substrates and with the enzymes p60c
      Src Src kinase, EGFR kinase, YOP protein tyrosine phosphatase, as well as acid
      and alkaline phosphatases, thereby demonstrating a broad application potential.
      The steady-state fluorescence changed by a factor of up to 7 in the course of the
      enzymatic reaction, which allowed for a sufficient sensitivity of continuous
      monitoring in steady-state experiments. The fluorescence lifetimes (and
      intensities) were found to be rather constant for the phosphotyrosine peptides
      (ca. 300 ns in aerated water), while those of the unphosphorylated peptides were
      as short as 40 ns (at pH 7) and 7 ns (at pH 13) as a result of intramolecular
      quenching. Owing to the exceptionally long fluorescence lifetime of Dbo, the
      assays were alternatively performed by using nanosecond time-resolved
      fluorescence (Nano-TRF) detection, which leads to an improved discrimination of
      background fluorescence and an increased sensitivity. The potential for inhibitor
      screening was demonstrated through the inhibition of acid and alkaline
      phosphatases by molybdate.

PMID- 18044895
TI  - Characterization of pore structure in metal-organic framework by small-angle X
      ray scattering.
AB  - MOF-5-like crystals were studied by small-angle X-ray scattering (SAXS) to
      reveal, both quantitatively and qualitatively, their real structural details,
      including pore surface characteristics, pore shape, size distribution, specific
      surface area (SSA), spatial distribution, and pore-network structure. A combined
      SAXS and wide-angle X-ray scattering (WAXS) experiment was conducted to
      investigate the variation of the pore structure with the MOF-5 crystalline phase
      produced at different cooling rates. The SSA of the MOF-5 crystals synthesized
      herein spanned a broad range from approximately 3100 to 800 m2/g. The real pore
      structures were divided into two regimes. In regime I the material consisted
      mainly of micropores of radius approximately 8 A as well as mesopores of radius
      120 approximately 80 A. The structure in regime II was a fractal network of
      aggregated mesopores with radius >or=32 A as the monomer, reducing SSA and
      hydrogen uptake capacity at room temperature. The two regimes can be manipulated
      by controlling the synthesis parameters. The concurrent evolution of pore
      structure and crystalline phase during heating for solvent removal was also
      revealed by the in-situ SAXS/WAXS measurement. The understanding of the impact of
      the real pore structure on the properties is important to establish a favorable
      synthetic approach for markedly improving the hydrogen storage capacity of MOF-5.

PMID- 18044896
TI  - Stable aqueous dispersion of ZnO quantum dots with strong blue emission via
      simple solution route.
AB  - The aqueous dispersion of ZnO quantum dots (QDs) with strong blue emission
      (quantum yield of 76%) was synthesized through a simple solution route. The water
      stability of such QDs is provided by the hydroxyl groups on their surface, and
      the strong blue emission is suggested to arise from the formation of surface
      ZnO/oleic acid complexes. Under irradiation, these complexes are thought to
      absorb the excitation light with 3.54 eV and then generate the blue emission with
      2.82 eV.

PMID- 18044897
TI  - Factors controlling adsorption equilibria from solution onto solid surfaces: the
      uptake of cinchona alkaloids on platinum surfaces.
AB  - The room-temperature adsorption of four closely related cinchona alkaloids and
      three reference quinoline-based compounds from CCl4 solutions onto a
      polycrystalline platinum surface was characterized by in situ reflection
      absorption infrared spectroscopy (RAIRS). The adsorption equilibrium constants
      (Kads) were found to follow the sequence cinchonine > quinidine > cinchonidine >
      quinine > 6-methoxyquinoline > lepidine > quinoline. Some of this ordering can be
      explained by differences in solubility, but quinidine displays a much larger Kads
      than expected on the basis of its large relative solubility; bonding to the
      surface must also play a role in determining its behavior. It was determined that
      each alkaloid binds differently on Pt at saturation coverages. While the
      quinoline ring of cinchonidine tilts along its long axis to optimize pi-pi
      intermolecular interactions, in cinchonine it tilts along the short axis and
      bonds through the lone electron pair of the nitrogen atom instead, and both
      quinine and quinidine exhibit additional bonding via the methoxy oxygen atom at
      intermediate concentrations. Perhaps a more surprising result from this work is
      the fact that cinchonine displays a higher Kads than cinchonidine, quinine, or
      quinidine even though, according to previous work, it can be easily displaced
      from the surface by any of those other cinchona alkaloids. A full explanation of
      these observations requires consideration of the solvent above the adsorbed
      species.

PMID- 18044898
TI  - Characterization of the covalently bound anionic flavin radical in monoamine
      oxidase a by electron paramagnetic resonance.
AB  - It was recently suggested that partially reduced monoamine oxidase (MAO) A
      contains an equilibrium mixture of an anionic flavin radical and a tyrosyl
      radical (Rigby, S. E.; et al. J. Biol. Chem. 2005, 280, 4627-4632). These
      observations formed the basis for a revised radical mechanism for MAO. In
      contrast, an earlier study of MAO B only found evidence for an anionic flavin
      radical (DeRose, V. J.; et al. Biochemistry 1996, 35, 11085-11091). To resolve
      the discrepancy, we have performed continuous-wave electron paramagnetic
      resonance at 94 GHz (W-band) on the radical form of MAO A. A comparison with d
      amino acid oxidase (DAAO) demonstrates that both enzymes only contain anionic
      flavin radicals. Pulsed electron-nuclear double resonance spectra of the two
      enzymes recorded at 9 GHz (X-band) reveal distinct hyperfine coupling patterns
      for the two flavins. Density functional theory calculations show that these
      differences can be understood in terms of the difference at C8alpha of the
      isoalloxazine ring. DAAO contains a noncovalently bound flavin whereas MAO A
      contains a flavin covalently bound to a cysteinyl residue at C8alpha. The similar
      electronic structures and hydrophobic environments of MAO and DAAO, and the
      similar structural motifs of their substrates suggest that a direct hydride
      transfer catalytic mechanism established for DAAO (Umhau, S.; et al. Proc. Natl.
      Acad. Sci. U.S.A. 2000, 97, 12463-12468) should be considered for MAO.

PMID- 18044900
TI  - Star-shaped oligo(p-phenylenevinylene) substituted hexaarylbenzene: purity,
      stability, and chiral self-assembly.
AB  - An oligo(p-phenylenevinylene) (OPV)-substituted hexaarylbenzene has been
      synthesized and fully characterized. Recycling gel permeation chromatography
      appeared to be a powerful technique to obtain the OPV molecules in a very pure
      form. X-ray analysis and polarization optical microscopy revealed that the OPV
      molecule is plastic crystalline at room temperature with an ordered columnar
      superstructure. In apolar solvents, the molecules self-assemble via a highly
      cooperative fashion into right-handed chiral superstructures, which are stable
      even at high temperatures and low concentration. Atomic force microscopy revealed
      right-handed fibers with a diameter of 6 nm, indicating pi-stacked aggregates; on
      a silicon oxide substrate, supercoiled chiral structures were observed. STM
      studies on a liquid-solid interface showed that the star-shaped OPV molecule
      forms an organized monolayer having a chiral hexagonal lattice.

PMID- 18044899
TI  - Routes to covalent catalysis by reactive selection for nascent protein
      nucleophiles.
AB  - Reactivity-based selection strategies have been used to enrich combinatorial
      libraries for encoded biocatalysts having revised substrate specificity or
      altered catalytic activity. This approach can also assist in artificial evolution
      of enzyme catalysis from protein templates without bias for predefined catalytic
      sites. The prevalence of covalent intermediates in enzymatic mechanisms suggests
      the universal utility of the covalent complex as the basis for selection.
      Covalent selection by phosphonate ester exchange was applied to a phage display
      library of antibody variable fragments (scFv) to sample the scope and mechanism
      of chemical reactivity in a naive molecular library. Selected scFv segregated
      into structurally related covalent and noncovalent binders. Clones that reacted
      covalently utilized tyrosine residues exclusively as the nucleophile. Two motifs
      were identified by structural analysis, recruiting distinct Tyr residues of the
      light chain. Most clones employed Tyr32 in CDR-L1, whereas a unique clone (A.17)
      reacted at Tyr36 in FR-L2. Enhanced phosphonylation kinetics and modest amidase
      activity of A.17 suggested a primitive catalytic site. Covalent selection may
      thus provide access to protein molecules that approximate an early apparatus for
      covalent catalysis.

PMID- 18044901
TI  - Crucial role of fluorescence in the solid-state thermochromism of
      salicylideneanilines.
AB  - The thermochromism of salicylideneanilines in the solid state has been so far
      explained only in terms of the temperature-induced change of light absorption,
      which is caused by the shift of the tautomeric equilibrium between the enol and
      cis-keto forms. In this study, we measured variable temperature diffuse
      reflectance and fluorescence spectra of the crystalline powders of
      salicylideneanilines. We also determined their fluorescence quantum yields. The
      chromaticity coordinates at each temperature were calculated from these data and
      compared to the perceived colors of the powders. We found that the temperature
      induced shift of the tautomeric equilibrium is not the main cause of the
      thermochromic color change of the thermochromic crystals and that the
      thermochromism can be explained only by taking account of the temperature-induced
      change of fluorescence.

PMID- 18044902
TI  - The lyngbyatoxin biosynthetic assembly line: chain release by four-electron
      reduction of a dipeptidyl thioester to the corresponding alcohol.
AB  - In comparison with the large number of nonribosomal peptide synthetases (NRPSs)
      that release their peptide products by hydrolytic cleavage of the peptide carrier
      protein (PCP) bound thioester, there are relatively few NRPSs that have been
      shown to use a nicotinamide cofactor to reduce this PCP-peptidyl thioester to an
      aldehyde or imine moiety. This work describes the first example of a reductase
      domain within a NRPS scaffold shown to reduce a PCP-peptidyl thioester to the
      corresponding primary alcohol, via an aldehyde intermediate, using two
      equivalents of reduced nicotinamide adenine dinucleotide phosphate (NADPH). By
      employing a ketone mimic of the aldehyde intermediate, as well as a specifically
      deuterated NADPH, it was further demonstrated that the pro-S hydride of the
      cofactor is transferred to the re face of the carbonyl group.

PMID- 18044904
TI  - Base-promoted reactions of dichlorocarbene adducts of cyclic enamines: a new
      route to annulated pyrroles.
AB  - Treatment of the gem-dihalogenocyclopropanes 1-5 with potassium tert-butoxide or
      LDA results in the formation of the corresponding and annulated pyrroles 13-17,
      respectively.

PMID- 18044905
TI  - A convenient and general iron-catalyzed hydrosilylation of aldehydes.
AB  - A general and highly chemoselective hydrosilylation of aldehydes using iron
      catalysts is reported. Fe(OAc)2 in the presence of tricyclohexylphosphine as
      ligand and polymethylhydrosiloxane (PMHS) as an economical hydride source forms
      an efficient catalyst system for the hydrosilylation of a variety of aldehydes.
      Aryl, heteroaryl, alkyl and alpha,beta-unsaturated aldehydes are successfully
      reduced to the corresponding primary alcohols. Broad substrate scope and high
      tolerance against several functional groups make the process synthetically
      useful.

PMID- 18044906
TI  - Open-shell singlet character of cyclacenes and short zigzag nanotubes.
AB  - The electronic ground states of [n]cyclacenes, as well as short-zigzag nanotubes,
      computed at unrestricted broken spin-symmetry density functional theory (UBS
      DFT), were found to be open-shell singlets, rather than triplets. Computations
      for [6]cyclacene at complete active space self-consistent field (CASSCF) and
      multireference perturbation theory (MRMP2) levels support this conclusion. Along
      with strain, the radical character of the open-shell singlet with
      antiferromagnetically coupled electron spins may contribute to the difficulties
      in synthesizing [n]cyclacenes.

PMID- 18044907
TI  - Copper(II) carboxylate-promoted intramolecular carboamination of alkenes for the
      synthesis of polycyclic lactams.
AB  - The copper(II) carboxylate-promoted intramolecular carboamination reactions of
      variously substituted gamma-alkenyl amides have been investigated. These
      oxidative cyclization reactions efficiently provide polycyclic lactams, useful
      intermediates in nitrogen heterocycle synthesis, in good to excellent yields. The
      efficiency of the carboamination process is dependent upon the structure of the
      amide backbone as well as the nitrogen substituent.

PMID- 18044908
TI  - Allocolchicines via intramolecular Nicholas reactions: the synthesis of NSC
      51046.
AB  - Biaryl propargyl acetate hexacarbonyldicobalt complexes (4) undergo Lewis acid
      mediated Nicholas reactions with a remote arene function to afford
      dibenzocycloheptyne complexes (9). Reductive decomplexation based on a
      hydrosilylation-protodesilylation protocol is facile, and the 1,2,3,9
      tetramethoxy case can be converted to NSC 51046 ((S)-N-acetylcolchicinol methyl
      ether, 3).

PMID- 18044909
TI  - Facile synthesis of naphthoquinone spiroketals by diastereoselective oxidative [3
      + 2] cycloaddition.
AB  - A highly selective oxidative [3 + 2] cycloaddition of chiral enol ethers and
      hydroxynaphthoquinone is described. This convergent strategy is amenable to an
      enantioselective synthesis of beta-rubromycin and related naphthoquinone
      spiroketals. Several compounds were found to inhibit DNA-polymerase and
      telomerase in a manner resembling alpha-rubromycin and beta-rubromycin.

PMID- 18044910
TI  - Chemoenzymatic synthesis of (S)-hexafluoroleucine and (S)-tetrafluoroleucine.
AB  - We have developed a short chemoenzymatic synthesis for both (S)-5,5,5,5',5',5'
      hexafluoroleucine (Hfl) and (S)-5,5,5',5'-tetrafluoroleucine (Qfl) on gram scale.
      Qfl was incorporated into a peptide using standard solid-phase peptide synthesis
      protocols to measure its helix propensity. The helix propensity for Qfl is 0.68
      kcal.mol-1 more favorable compared to Hfl.

PMID- 18044911
TI  - Remarkable effect of N-substituent on enantioselective ruthenium-catalyzed
      propargylation of indoles with propargylic alcohols.
AB  - Ruthenium-catalyzed enantioselective propargylation of indoles with propargylic
      alcohols affords the corresponding beta-propargylated indoles in good yields with
      a high enantioselectivity (up to 95% ee). A remarkable effect of the nature of
      the N-substituent of indoles is observed for the enantioselectivity of the
      propargylated indoles. The preparative method described in this paper may provide
      a novel protocol for asymmetric Friedel-Crafts alkylation of indoles using
      propargylic alcohols as a new type of electrophiles.

PMID- 18044912
TI  - Model studies of beta-scission ring-opening reactions of cyclohexyloxy radicals:
      application to thermal rearrangements of dispiro-1,2,4-trioxanes.
AB  - A DFT study of model cyclohexyloxy radicals (8a-c, 9) show that (a) the presence
      of an adjacent oxygen atom, and (b) alpha-substituents on the cyclohexyl ring,
      particularly methoxy, accelerate the rate of beta-scission ring-opening
      reactions. Consistent with theoretical results, thermolysis of the methoxy
      substituted dispiro-1,2,4-trioxane 10 afforded the structurally novel, 14
      membered macrocyclic keto lactone 11 as the major isolable product.

PMID- 18044913
TI  - A novel catechol-based universal support for oligonucleotide synthesis.
AB  - A novel universal support for deoxyribo- and ribonucleic acid synthesis has been
      developed. The support, constructed from 1,4-dimethoxycatechol, represents an
      improvement over existing universal supports because of its ability to cleave and
      deprotect under mild conditions in standard reagents. Because no nonvolatile
      additives are required for cleavage and deprotection, the synthesized
      oligonucleotides do not require purification prior to use in biochemical assays.
      Using reverse phase HPLC and electrospray mass spectroscopy, it was determined
      that oligonucleotides synthesized on the universal support (UL1) 3'
      dephosphorylate quickly (9 h in 28-30% ammonium hydroxide (NH4OH) at 55 degrees
      C, 2 h in 28-30% NH4OH at 80 degrees C, or <1 h in ammonium hydroxide/methylamine
      (1:1) (AMA) at 80 degrees C). Oligonucleotides used as primers for the polymerase
      chain reaction (PCR) assay were found to perform identically to control primers,
      demonstrating full biological compatibility. In addition, a method was developed
      for sintering the universal support directly into a filter plug which can be
      pressure fit into the synthesis column of a commercial synthesizer. The universal
      support plugs allow the synthesis of high-quality oligonucleotides at least 120
      nucleotides in length, with purity comparable to non-universal commercial
      supports and approximately 50% lower reagent consumption. The universal support
      plugs are routinely used to synthesize deoxyribo-, ribo-, 3'-modified, 5'
      modified, and thioated oligonucleotides. The flexibility of the universal support
      and the efficiency of 3'-dephosphorylation are expected to increase the use of
      universal supports in oligonucleotide synthesis.

PMID- 18044914
TI  - Semisynthesis of long-chain alkyl ether derivatives of sulfated oligosaccharides
      via dibutylstannylene acetal intermediates.
AB  - Long-chain alkyl ether derivatives of sulfated oligosaccharides were
      semisynthesized as follows: two naturally occurring red seaweed galactans
      (neutral agarose and kappa-carrageenan) were submitted to partial reductive
      hydrolysis to give neutral and sulfated oligosaccharide alditols. The neutral
      disaccharide alditol (1) and its trityl ether (5) were sulfated and/or alkylated
      through formation of their dibutylstannylene or (bis)dibutylstannylene acetals.
      In these reactions, the dibutylstannylene acetals of the terminal 1,2-diols in
      the alditol units were more reactive than those formed on the cis-diols of the
      galactopyranosidic units. This property allowed the regioselective monoalkylation
      of a neutral tetrasaccharide alditol (2), which contained eleven free hydroxyl
      groups, the highest selectivity ever observed with dibutylstannylene acetals. An
      alkylated/sulfated derivative (11) was also obtained through the regioselective
      alkylation of a naturally sulfated disaccharide alditol (10, a kappa-carrageenan
      derivative).

PMID- 18044915
TI  - On the mechanism and kinetics of radical reactions of epoxyketones and
      epoxynitriles induced by titanocene chloride.
AB  - The reactions of a series of epoxynitriles and epoxyketones induced by titanocene
      chloride have been studied. The kinetics of the decyanogenation of beta,gamma
      epoxynitriles with Ti(III) corresponds to a radical reaction (k25 approximately
      106 s-1), as demonstrated by competition experiments with H-transfer from 1,4
      cyclohexadiene (1,4-CHD) or PhSH or conjugate addition to acrylonitrile. The 5
      exo cyclization onto nitrile induced by Ti(III) is a radical reaction (k25
      approximately 107 s-1) as seen in competition experiments with H-transfer from
      PhSH or the titanocene-water complex. The iminyl or alkoxyl radicals generated by
      5-exo cyclization onto nitriles or ketones only undergo a reduction with Ti(III).
      This reaction overwhelms any alternative process, such as tandem cyclization onto
      alkenes or beta-scission. Iminyl radicals generated by 4-exo cyclizations onto
      nitriles undergo reduction with Ti(III) and beta-scission reaction in a ratio of
      96:4 when the alpha-substituent is CN. Alkoxyl radicals from 4-exo cyclizations
      onto ketone carbonyls undergo reduction with Ti(III) and beta-scission in a ratio
      of 60:40 when the alpha-substituent is COOR. In nearly all the reactions studied,
      the role of Ti(III) is triple: a radical initiator (homolytic cleavage of
      oxirane), a Lewis acid (coordination to CN or C=O), and a terminator (reduction
      of iminyl or alkoxyl radicals).

PMID- 18044916
TI  - Difluoromethyltrialkylammonium salts--their expeditious synthesis from
      chlorodifluoromethane and tertiary amines in the presence of concentrated aqueous
      sodium hydroxide. The catalytic process.
AB  - We found that difluorocarbene generated from chlorodifluoromethane with 50%
      aqueous sodium hydroxide reacts with lipophilic tertiary amines 1a-g giving
      difluoromethyltrialkylammonium chlorides 2a-g in high yields. Similarly,
      difluoromethyltrialkylammonium iodides 3h-l, nitrates 4h-k, or isothiocyanates
      5i,j were synthesized from hydrophilic tertiary amines 1h-l and the corresponding
      sodium or potassium salts. The process is catalytic with respect to the base
      used.

PMID- 18044917
TI  - Enantioselective pinacol coupling of aryl aldehydes catalyzed by chiral Salan
      Mo(IV) complexes.
AB  - Reported herein is the asymmetric pinacol coupling of aromatic aldehydes with
      chiral Salan-Mo(VI) dioxo complex as an effective precatalyst. Chiral diols were
      obtained with high diastereoselectivity and enantioselectivity up to 92/8 and
      95%, respectively. The possible mechanism of the pinacol coupling reaction with
      the catalytic system was investigated. The X-ray crystal structure of the
      precatalyst Mo(L3)O2 was determined and the oxidation state of the intermediate C
      was confirmed as +4 with X-ray photoelectron spectroscopy study. The proposed
      mechanism speculated the stereochemical outcome of the reaction, and a working
      model for the radical coupling of E was proposed, which explained the absolute
      configuration of the favored (S,S)-enantiomer of the dl isomer.

PMID- 18044918
TI  - IPy2BF4/HF-pyridine: a new combination of reagents for the transformation of
      partially unprotected thioglycosides and n-pentenyl glycosides to glycosyl
      fluorides.
AB  - The combination of bis(pyridinium)iodonium (I) tetrafluoroborate (IPy2BF4), and
      hydrogen fluoride pyridine (HF-py) forms an iodine monofluoride (IF) synthetic
      equivalent that can be used in the preparation of partially unprotected glycosyl
      fluorides from partially unprotected n-pentenyl glycosides and thioglycosides,
      thus avoiding the need for the protection/deprotection steps normally required in
      that transformation.

PMID- 18044919
TI  - Diastereoselective production of homoallylic alcohols bearing quaternary centers
      from gamma-substituted allylic indiums and ketones.
AB  - Highly stereoselective In-employed addition of gamma-substituted allylic halides
      (cyclohexenyl halides, cinnamyl halides, and ethyl 4-bromocrotonate) to ketones
      is established to produce homoallyl alcohols bearing quaternary centers. The
      reactivity patterns and relative stability of allylic indiums were studied. The
      addition of water characteristically affected the reactions. Cyclohexenyl indium
      addition was completely disturbed, but a clear reaction was observed in the
      cinnamyl and crotonate-indium addition. In the case of ethyl 4-bromocrotonate, an
      interesting conversion of a gamma-adduct into an alpha-adduct was observed in
      anhydrous conditions.

PMID- 18044920
TI  - Unprecedented detection of enantiomerization pi-barriers due to restricted aryl
      torsion: case of 1,8-di-arylbiphenylenes.
AB  - Dynamic NMR spectroscopy allowed, for the first time, the determination of the pi
      barriers responsible for the enantiomerization processes in derivatives bearing
      two aryl substituents bonded to a planar framework: this could be achieved in the
      case of 1,8-di-m-tolylbiphenylene (1) and 1,8-di-m-xylylbiphenylene (2). In
      derivative 1, the three possible conformers predicted by DFT computations (anti
      in, syn, and anti-out) were detected, and in addition, the steric barrier
      responsible for their interconversion could be measured. The barriers predicted
      by DFT calculations were found in satisfactory agreement with experimental data.

PMID- 18044921
TI  - Synthesis of S-acetyl oligoarylenedithiols via Suzuki-Miyaura cross-coupling.
AB  - Oligoarylenes with three or four aromatic rings, bearing two S-acetylated
      mercaptomethyl groups in 1,3 position on one end of the polyaromatic system and
      presenting various functionalities on the other terminal ring, have been
      synthesized by the Suzuki-Miyaura cross-coupling reaction. The use of palladium
      complexes with a Buchwald's phosphine as ligand allowed us to perform this
      coupling reaction also in the presence of benzylic S-acetyl-protected
      functionalities on the aromatic halide. The obtained oligoarylenes are potential
      novel candidates for the generation of self-assembling monolayers on metal
      substrates.

PMID- 18044922
TI  - Nitrone [2+3]-cycloadditions in stereocontrolled synthesis of a potent proteasome
      inhibitor: (-)-omuralide.
AB  - A new stereocontrolled synthetic route to omuralide has been developed from
      methyl pyroglutamate. This route involves regio- and stereoselective N
      methylnitrone 1,3-dipolar cycloadditions to appropriate pyrrolinones, beta
      eliminations, and highly selective hydrogenations as the main steps.

PMID- 18044923
TI  - A rational protocol for the synthesis of arylated bipyridine ligands via a
      cycloaddition pathway.
AB  - A generic design principle for the preparation of a variety of substituted phenyl
      polypyridine ligands is described. These ligands are readily prepared by a
      regioselective [4+2] cycloaddition between electron-deficient dienes, such as 2,6
      disubstituted-1,3,4-triazines, and ethynyl-arenes or ethynyl-alkanes. Exceptional
      reactivity is found with electron-rich dienophiles bearing ethynylgallate or
      ethynylphenyldibutylamino groups. Two regioisomers are formed, the meta being
      preferred due to favorable pi-pi interactions in the transition state, while the
      para isomers are formed in low yields in most cases. The use of tert
      butylacetylene or N,N-dimethylamino-2-propyne, however, drives the reaction
      exclusively to the para isomer. Di-N,N-dibutylaminophenyl or isoquinoline ligands
      can also be produced in a single step by reverse Diels-Alder reactions. Cross
      coupling reactions of iodo-substituted ligands or their platinum(II) complexes
      under Pd(0) catalysis gives branched ligands and complexes bearing paraffin
      chains, electron-donor or electron-acceptor groups. The use of a chloro-Pt(II)
      complex of an iodo-functionalized ligand allows both halogens to be replaced by
      ethynyl groups by using different catalysts. This methodology readily
      accommodates various functional groups and has been successfully extended to
      systems containing a variety of donor/acceptor frameworks. All ligands strongly
      absorb in the near-UV and luminesce in solution at rt with quantum yields ranging
      from 0 to 66%. Excited state lifetimes are in the nanosecond range and the
      solvent effects are in keeping with singlet excited states mixed with charge
      transfer character. As deduced from spectroscopic and electrochemical studies,
      the di-n-butylamino derivatives are strong reductants in the excited state.

PMID- 18044924
TI  - Total syntheses of (-)-alpha-kainic acid and (+)-alpha-allokainic acid via
      stereoselective C-H insertion and efficient 3,4-stereocontrol.
AB  - Reported herein is a novel approach to the total syntheses of (-)-alpha-kainic
      acid and (+)-alpha-allokainic acid, where the stereochemistries on C(2), C(3),
      and C(4) of the pyrrolidine core were introduced efficiently and selectively. A
      regio- and stereoselective C-H insertion reaction was utilized to prepare the
      gamma-lactam as an intermediate. A Michael-type cyclization of phenylsulfone with
      a conjugated acetylenic ketone was developed to prepare the tricyclic ketone as a
      key intermediate for (-)-alpha-kainic acid. Subsequently, a stereoselective
      dephenylsulfonylation was carried out successfully to secure the cis relationship
      at C(3) and C(4) centers. An unprecedented acetylation on the phenylsulfone,
      followed by a stereoselective dephenylsulfonylation, secured the trans
      relationship at C(3) and C(4) centers in (+)-alpha-allokainic acid.

PMID- 18044925
TI  - Nitration versus nitrosation chemistry of menthofuran: remarkable fragmentation
      and dimerization pathways and expeditious entry into dehydromenthofurolactone.
AB  - The reaction chemistry of menthofuran (1), a toxic furan terpenoid from various
      mint oils, with nitric acid and nitrous acid has been investigated. Treatment of
      1 with nitric acid afforded a 1:1 mixture of the bisfuran derivatives 5 and 6,
      resulting from the unexpected cleavage of the furan into two carbonyl fragments
      (3-methylcyclohexanone and hydroxyacetone) and their subsequent trapping by
      unreacted 1. Under conditions of high dilution, the nitrofuran derivative 7 was
      formed instead as the major reaction product. During investigation of this
      chemistry, it was found that oxidation of 1 with DDQ led to the important
      fragrant monoterpenoid 4 [dehydromenthofurolactone (anhydro Woodward-Eastman
      lactone)] in 44% yield. Exposure of 1 to nitrite ions at pH 3 afforded a
      completely different type of products, encompassing the known lactone 14, the
      lactam 15, and the remarkable dimer 16, bearing a N-hydroxy-2-pyrrolinone moiety
      linked to a nitrooximinofuran unit by an oxygen bridge. By using a combined
      spectroscopic and DFT approach, the constitution and configuration of 16 could be
      determined. These results fill a gap in the chemistry of furan compounds and
      describe routes to menthofuran-derived scaffolds of potential synthetic and
      biomedical relevance.

PMID- 18044926
TI  - Highly efficient synthesis of optically pure 5,5',6,6',7,7',8,8'-octahydro-1,1'
      bi-2-naphthol and -naphthylamine derivatives by partial hydrogenation of 1,1'
      binaphthyls with carbon nanofiber supported ruthenium nanoparticles.
AB  - Use of Ru/CNF-P, nanoruthenium particles dispersed on a nanocarbon fiber support,
      realizes highly efficient catalytic partial hydrogenation of 1,1'-bi-2-naphthol
      and -naphthyl-amine derivatives. The reactions proceed in high turnover numbers
      without racemization of the axial chirality, offering a practical procedure for
      the production of optically pure 5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyls
      in good to high yields.

PMID- 18044927
TI  - An efficient synthesis of quaterrylenedicarboximide NIR dyes.
AB  - Quaterrylenedicarboximides were prepared from 9-bromoperylene-3,4-dicarboximides
      by palladium-catalyzed coupling with 3-perylene boronic ester, followed by
      oxidative cyclodehydrogenation of the resulting perylene-perylenedicarboximide
      dyads with iron(III) chloride. The quaterrylenedicarboximides, described here,
      are highly photochemically and thermally stable dyes, which may be useful as
      green NIR dyes (lambdamax = 735 nm) and as building blocks for the synthesis of
      higher rylene dyes.

PMID- 18044928
TI  - An improved Cu-based catalyst system for the reactions of alcohols with aryl
      halides.
AB  - The use of 3,4,7,8-tetramethyl-1,10-phenanthroline (Me(4)Phen) as a ligand
      improves the Cu-catalyzed cross-coupling reactions of aryl iodides and bromides
      with primary and secondary aliphatic, benzylic, allylic, and propargylic
      alcohols. Most importantly, by employing this catalyst system, the need to use an
      excessive quantity of the alcohol coupling partner is alleviated. The relatively
      mild conditions, short reaction times, and moderately low catalyst loading allow
      for a wide array of functional groups to be tolerated on both the electrophilic
      and nucleophilic coupling partners.

PMID- 18044929
TI  - Cu(I)-catalyzed intramolecular cyclization of alkynoic acids in aqueous media: a
      "click side reaction".
AB  - Alkynoic acids, in particular, 4-pentynoic acid derivatives, undergo
      intramolecular cyclizations to enol lactones under reaction conditions typically
      applied for the Cu(I)-catalyzed cycloaddition of terminal alkynes and azides
      (click chemistry). Starting from appropriate alkynoic acid derivatives, either
      enol lactones or 1,2,3-triazole click products can be obtained selectively by
      Cu(I) catalysis in aqueous media.

PMID- 18044930
TI  - The scope and mechanism of phosphonium-mediated S(N)Ar reactions in heterocyclic
      amides and ureas.
AB  - An efficient "one-step" synthesis of cyclic amidines and guanidines has been
      developed. Treatment of cyclic amides and ureas with benzotriazol-1
      yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP), base, and nitrogen
      nucleophiles leads to the formation of the corresponding cyclic amidines and
      guanidines, typically in good to excellent yields. This method has also been used
      to prepare heteroaryl ethers and thioethers using phenol and thiophenol
      nucleophiles. Time course NMR and HPLC-MS studies have facilitated explicit
      characterization of the proposed intermediates (the phosphonium salt and HOBt
      adduct); the data reveal a stepwise reaction pathway.

PMID- 18044931
TI  - Lewis acid-mediated rearrangement of activated cyclic amines: a facile synthetic
      protocol for the preparation of amino carbonyl compounds.
AB  - Ring opening of activated cyclic amines to produce amino carbonyl compounds has
      been studied in the presence of Lewis acids. Whereas five- and six-membered rings
      cleave and rearrange via a 1,2-hydride shift, reaction in three- and four
      membered rings takes place via a C-C bond migration. In the case of a three
      membered ring, a wide variety of Lewis acids proved to be effective for the
      reaction. Base-induced ring opening of activated alpha,alpha-disubstituted
      azetidinemethanol and its mechanistic aspects have been studied.

PMID- 18044932
TI  - Stereoselective total syntheses of three Lycopodium alkaloids, (-)-magellanine,
      (+)-magellaninone, and (+)-paniculatine, based on two Pauson-Khand reactions.
AB  - The total syntheses of (-)-magellanine, (+)-magellaninone, and (+)-paniculatine
      were completed from diethyl l-tartrate via the common intermediate in a
      stereoselective manner. The crucial steps in these syntheses involved two
      intramolecular Pauson-Khand reactions of enynes: the first Pauson-Khand reaction
      constructed the bicyclo[4.3.0] carbon framework, the corresponding A and B rings
      of these alkaloids in a highly stereoselective manner, whereas the second Pauson
      Khand reaction stereoselectively produced the bicyclo[3.3.0]skeleton, which could
      be converted into the C and D rings of the target natural products.

PMID- 18044933
TI  - Highly enantioselective aza-Henry reaction of N-tosyl imines catalyzed by N,N'
      dioxide-Cu(I) complexes.
AB  - The N,N'-dioxide-Cu(I) complexes have been developed to catalyze the addition of
      nitromethane to N-tosyl aldimines. The aza-Henry reaction proceeds smoothly
      affording the corresponding nitro amines in good yields with high
      enantioselectivities. A catalytic cycle is proposed to explain the origin of
      reactivity.

PMID- 18044934
TI  - Interfacial oil droplets.
AB  - Very small, discrete oil droplets can form at the solid-liquid interface. We
      demonstrate this effect through formation of decane droplets at the interface
      between an aqueous ethanol solution and silicon wafers that have been made
      hydrophobic through self-assembly of octadecyltrichlorosilane (OTS). The droplets
      have a lens-like shape; the shape is approximately a spherical cap with a contact
      angle < 25 degrees. The heights of the droplets are about 2-50 nm, and diameters
      at the three-phase boundary are about 100-600 nm in 25% ethanol solution. The
      size and contact angle can be varied by changing the ethanol concentration. The
      contact angle of the very small droplets (height < 20 nm) is similar to the
      contact angle of macroscopic droplets (height approximately equal to 1 mm), so
      the line tension is very small. The droplets are only stable for a few hours:
      they gradually lose mass, presumably through Ostwald ripening. The drop perimeter
      is not pinned during ripening but retreats across the solid. We form the droplets
      by direct adsorption from an emulsion; evidence for adsorption is obtained by
      comparing the drop volumes in bulk to the volumes at the interface. The droplet
      sizes are obtained by dynamic light scattering and atomic force microscopy.

PMID- 18044935
TI  - Self-assembly of fatty acids and hydroxyl derivative salts.
AB  - We report the dispersions of a fatty acid and hydroxyl derivative salts in
      aqueous solutions that were further used to produce foams and emulsions. The
      tetrabutyl-ammonium salts of palmitic acid, 12-hydroxy stearic acid, and omega
      hydroxy palmitic acid formed isotropic solutions of micelles, whereas the
      ethanolamine salts of the same acids formed turbid birefringent lamellar
      solutions. The structure and dimension of those phases were confirmed by small
      angle neutron scattering and NMR. Micelles exhibited a surprisingly small radius
      of about 20 A, even for hydroxyl fatty acids, suggesting the formation of
      hydrogen bonds between lipids in the core of the micelles. In the case of
      ethanolamine salts of palmitic and 12-hydroxy stearic acids, the lipids were
      arranged in bilayers, with a phase transition from gel to fluid upon heating,
      whereas for omega-hydroxy palmitic acid, monolayers formed in accordance with the
      bola shape of this lipid. Foams and emulsions produced from ethanolamine salt
      solutions were more stable than those obtained from tetrabutyl-ammonium salt
      solutions. We discuss these results in terms of counterion size, lipid molecular
      shape, and membrane curvature.

PMID- 18044936
TI  - Adhesion and stable low friction provided by a subnanometer-thick monolayer of a
      natural polysaccharide.
AB  - Using a surface forces apparatus, we have investigated the adhesive and
      lubrication forces of mica surfaces separated by a molecularly thin, subnanometer
      film of a high-molecular-weight (2.3 MDa) anionic polysaccharide from the algae
      Porphyridium sp. adsorbed from aqueous solution. The adhesion and friction forces
      of the confined biopolymer were monitored as a function of time, shearing
      distance, and driving velocity under a large range of compressive loads
      (pressures). Although the thickness of the dilute polysaccharide was <1 nm, the
      friction was low (coefficient of friction = 0.015), and no wear was ever observed
      even at a pressure of 110 atm over 3 decades of velocity, so long as the shearing
      distances were less than twice the contact diameter. Atomic force microscopy in
      solution shows that the biopolymer is able to adsorb to the mica surface but
      remains mobile and easily dragged upon shearing. The adhesion (adsorption) of
      this polysaccharide even to negatively charged surfaces, its stable low friction,
      its robustness (high-load carrying capacity and good wear protection), and the
      weak (logarithmic) dependence of the friction force on the sliding velocity make
      this class of polyelectrolytes excellent candidates for use in water-based
      lubricant fluids and as potential additives to synovial fluid in joints and other
      biolubricating fluids. The physical reasons for the remarkable tribological
      properties of the ultrathin polysaccharide monolayer are discussed and appear to
      be quite different from those of other polyelectrolytes and proteins that act as
      thick "polymer brush" layers.

PMID- 18044937
TI  - Fluorescence study of the solvation of fluorescent probes prodan and laurdan in
      poly(epsilon-caprolactone)-block-poly(ethylene oxide) vesicles in aqueous
      solutions with tetrahydrofurane.
AB  - Steady-state and time-resolved fluorescence measurements were used to study the
      relaxation of the microenvironment of hydrophobic probes 6-propionyl-2
      (dimethylamino)naphthalene (prodan) and 6-dodecanoyl-2-(dimethylamino)naphthalene
      (laurdan) in systems containing vesicles formed by the amphiphilic diblock
      copolymer poly(epsilon-caprolactone)-block-poly(ethylene oxide) (PCL-PEO) and
      water/tetrahydrofurane (THF) solvent mixtures. It was found that in case of
      prodan, both steady-state and time-resolved emission spectra were composed of two
      subspectra corresponding to the emission of prodan molecules located (i) in
      fairly rigid (effectively viscous) and hydrophobic domains of the vesicles close
      to the PCL/PEO interface and (ii) in a more polar and less viscous medium (in the
      bulk solution). The fraction of the emission from the more polar microenvironment
      increases with increasing content of THF in the system. Laurdan, in contrast to
      prodan, appeared to be solubilized preferentially in the hydrophobic domains up
      to 30 vol % of THF content, and its emission spectra changed only due to swelling
      of hydrophobic PCL domains by added THF. The study shows that the analysis of the
      time-resolved emission from a probe distributed in two media is, in principle,
      possible, but it is quite complex and appreciably less accurate, and the
      relaxation times are ill-defined averages of several processes. The bimodal or
      shoulder-containing time-resolved spectra have to be decomposed in pertinent time
      resolved subspectra and treated separately. Another important result of the study
      is a piece of knowledge concerning the motion of the probe with respect to the
      vesicle. In the studied complex system, not only the relaxation of the solvent
      and reorganization of polymer segments around the fluorescent headgroup of the
      probe affect the emission but also a lateral motion of the probe with respect to
      the nanoparticle within the lifetime of the excited state contributes
      significantly to the relaxation and to the relatively slow time-resolved Stokes
      shift.

PMID- 18044938
TI  - Chemical template directed iodine patterns on the octadecyltrichlorosilane
      surface.
AB  - A carboxylic-terminated nanometer-scale chemical pattern on an
      octadecyltrichlorosilane (OTS) surface can guide the deposition and
      crystallization of iodine, forming an iodine pattern on the chemical pattern. The
      iodine in the pattern is gel-like when fabricated by the solution-deposit method.
      In contrast, a dendritic, snowflake-shaped polycrystalline iodine sheet is formed
      by the vapor-phase condensation method. The data demonstrate that iodine is a
      good tracing and visualizing agent for studying liquid behavior at the nano
      scale. The topography of the iodine stain reveals that the "coffee ring" effect
      can be suppressed by reducing the pattern size and increasing the evaporation
      rate. The chemical template-bound iodine pattern has an unusually low vapor
      pressure and it can withstand prolonged baking at elevated temperature, which
      differs significantly from bulk iodine crystals.

PMID- 18044939
TI  - Absence of ethanol-induced interdigitation in supported phospholipid bilayers on
      silica surfaces.
AB  - Membranes prepared by the adsorption of phospholipid vesicles on solid supports
      are much-used model systems in biomedical research. However, there is
      accumulating evidence that such membranes may not always be equivalent to the
      free-standing cellular membranes that they are modeling. In the present study,
      sonicated DOPC/DOPS (80/20 mol %) vesicles were adsorbed on hydrophilic silica
      surfaces, a system that has been demonstrated to produce confluent bilayers. In
      addition, pure DOPC and DLPC membranes were studied. It is demonstrated that
      ethanol-induced membrane interdigitation, as demonstrated for free-standing
      bilayers, does not occur in these supported membranes.

PMID- 18044940
TI  - Surface dilatational elasticity of poly(oxy ethylene)-based surfactants by
      oscillation and relaxation measurements of sessile bubbles.
AB  - Surface dilatational elasticities and viscosities have been measured by means of
      the axisymmetric bubble shape method. Two different techniques using sinusoidal
      oscillations and step relaxations have been used, and the results are treated by
      means of the bulk/surface diffusional exchange model. Three different nonionic
      surfactants based on poly(oxy ethylene) as the hydrophilic group have been used:
      one simple surfactant, Brij 35, and two block copolymers, Pluronic F68 and P9400.
      Step relaxation and oscillation give mostly the same limiting surface
      dilatational elasticities, but step relaxation is a more model-dependent method.
      In the cases where the bulk/surface diffusion model is correct, the two methods
      give the same results, but otherwise step relaxation gives average values of the
      limiting elasticity E0 and the typical relaxation frequency omega0. Limiting
      elasticities up to ca. 25 mN m(-1)have been found for these substances. The
      surface/bulk diffusion model describes quite well the two relatively hydrophilic
      substances Brij 35 and F68, especially at low concentrations, but less so for the
      more hydrophobic P9400. The surface dilatational elasticity as a function of the
      surface pressure of the surface-active polymers goes through at least one maximum
      as a result of surface conformational changes.

PMID- 18044941
TI  - Kinetic restriction of simple gases in porous carbons: transition-state theory
      study.
AB  - The separation of simple gases such as N2, Ar, CO2, and CH4 is an industrially
      important problem, particularly for the mitigation of greenhouse emissions.
      Furthermore, these gases are widely accepted as standard probing gases for the
      characterization of the microstructure of porous solids. However, a consistent
      set of microstructural parameters of a microporous solid determined from the use
      of adsorption measurements of these different gases is not always achieved
      because of differences in their pore accessibility. This is a long-standing and
      poorly understood problem. Here, we present the calculated results of the
      crossing time of N2, Ar, CO2, and CH4 between two neighboring cages through a
      constricted window in a realistic structural model of saccharose char, generated
      from hybrid reverse Monte Carlo (HRMC) simulation (Nguyen, T. X.; Bhatia, S. K.;
      Jain, S. K.; Gubbins, K. E. Mol. Simul. 2006, 32, 567-577) using transition state
      theory (TST), as described in our recent work (Nguyen, T. X.; Bhatia, S. K. J.
      Phys. Chem. 2007, 111, 2212-2222). The striking feature in these results is that
      whereas very fast diffusion of carbon dioxide within the temperature range of 273
      343 K, with crossing time on the molecular dynamics scale (10-4-10-6 s), leads to
      instantaneous equilibrium and no hysteresis on the experimental time scale,
      slower diffusion of Ar and N2 at the low temperature of analysis indicates an
      accessibility problem. These results rationalize the experimental results of
      hysteresis for N2 at 77 K and Ar at 87 K but not for CO2 at 273 K in Takeda 3 A
      carbon molecular sieves. Furthermore, it is shown that CH4 diffusion through
      narrow pore mouths can be hindered even at ambient temperature. Finally, we show
      that the use of pore size and wall thickness distributions extracted from the
      adsorption of Ar at 87 K using the finite wall thickness (FWT) model (Nguyen, T.
      X.; Bhatia, S. K. Langmuir 2004, 20, 3532-3535 and Nguyen, T. X.; Bhatia, S. K.
      J. Phys. Chem. B 2004, 108, 14032-14042) provides the correct prediction of
      experimental CO2 adsorption in BPL and PCB carbons whereas that from N2 at 77 K
      gives a significant underprediction for both CO2 and CH4 in the BPL carbon. These
      trends are in excellent agreement with those predicted using the calculated
      crossing times.

PMID- 18044942
TI  - Temperature-dependent solvation dynamics of water in sodium bis(2
      ethylhexyl)sulfosuccinate/isooctane reverse micelles.
AB  - In this paper, for the first time, we report a detailed study of the temperature
      dependent solvation dynamics of a probe fluorophore, coumarin-500, in
      AOT/isooctane reverse micelles (RMs) with varying degrees of hydration (w0) of 5,
      10, and 20 at four different temperatures, 293, 313, 328, and 343 K. The average
      solvation time constant becomes faster with the increase in w0 values at a
      particular temperature. The solvation dynamics of a RM with a fixed w0 value also
      becomes faster with the increase in temperature. The observed temperature-induced
      faster solvation dynamics is associated with a transition of bound- to free-type
      water molecules, and the corresponding activation energy value for the w0 = 5
      system has been found to be 3.4 kcal mol-1, whereas for the latter two systems,
      it is approximately 5 kcal mol-1. Dynamic light scattering measurements indicate
      an insignificant change in size with temperature for RMs with w0 = 5 and 10,
      whereas for a w0 = 20 system, the hydrodynamic diameter increases with
      temperature. Time-resolved fluorescence anisotropy studies reveal a decrease in
      the rotational restriction on the probe with increasing temperature for all
      systems. Wobbling-in-cone analysis of the anisotropy data also supports this
      finding.

PMID- 18044943
TI  - Macro- to nanoscale wear prevention via molecular adsorption.
AB  - As the size of mechanical systems shrinks from macro- to nanoscales, surface
      phenomena such as adhesion, friction, and wear become increasingly significant.
      This paper demonstrates the use of alcohol adsorption as a means of continuously
      replenishing the lubricating layer on the working device surfaces and elucidates
      the tribochemical reaction products formed in the sliding contact region.
      Friction and wear of native silicon oxide were studied over a wide range of
      length scales from macro- to nanoscales using a ball-on-flat tribometer
      (millimeter scale), sidewall microelectromechanical system (MEMS) tribometer
      (micrometer scale), and atomic force microscopy (nanometer scale). In all cases,
      the alcohol vapor adsorption successfully lubricated and prevented wear. Imaging
      time-of-flight secondary ion mass spectrometry analysis of the sliding contact
      region revealed that high molecular weight oligomeric species were formed via
      tribochemical reactions of the adsorbed linear alcohol molecules. These
      tribochemical products seemed to enhance the lubrication and wear prevention. In
      the case of sidewall MEMS tests, the lifetime of the MEMS device was radically
      increased via vapor-phase lubrication with alcohol.

PMID- 18044944
TI  - Polysugar-stabilized Pd nanoparticles exhibiting high catalytic activities for
      hydrodechlorination of environmentally deleterious trichloroethylene.
AB  - In this paper, we present a straightforward and environmentally friendly aqueous
      phase synthesis of small Pd nanoparticles (approximately 2.4 nm under the best
      stabilization) by employing a "green", inexpensive, and
      biodegradable/biocompatible polysugar, sodium carboxymethylcellulose (CMC), as a
      capping agent. The Pd nanoparticles exhibited rather high catalytic activity
      (observed pseudo-first-order reaction kinetic rate constant, k(obs), is up to 828
      L g(-1) min(-1)) for the hydrodechlorination of environmentally deleterious
      trichloroethene (TCE) in water. Fourier transform IR (FT-IR) spectra indicate
      that CMC molecules interact with the Pd nanoparticles via both carboxyl (-COO-)
      and hydroxyl (-OH) groups, thereby functioning to passivate the surface and
      suppress the growth of the Pd nanoparticles. Hydrodechlorination of TCE using
      differently sized CMC-capped Pd nanoparticles as catalyst was systematically
      investigated in this work. Both the catalytic activity (k(obs)) and the surface
      catalytic activity (turnover frequency, TOF) of these CMC-capped Pd nanoparticles
      for TCE degradation are highly size-dependent. This point was further verified by
      a comparison of the catalytic activities and surface catalytic activities of CMC
      capped Pd nanoparticles with those of beta-D-glucose-capped Pd and neat Pd
      nanoparticles for TCE degradation.

PMID- 18044945
TI  - Composite block copolymer stabilized nanoparticles: simultaneous encapsulation of
      organic actives and inorganic nanostructures.
AB  - We describe the preparation and characterization of hybrid block copolymer
      nanoparticles (NPs) for use as multimodal carriers for drugs and imaging agents.
      Stable, water-soluble, biocompatible poly(ethylene glycol)-block-poly(epsilon
      caprolactone) NPs simultaneously co-encapsulating hydrophobic organic actives
      (beta-carotene) and inorganic imaging nanostructures (Au) are prepared using the
      flash nanoprecipitation process in a multi-inlet vortex mixer. These composite
      nanoparticles (CNPs) are produced with tunable sizes between 75 nm and 275 nm,
      narrow particle size distributions, high encapsulation efficiencies, specified
      component compositions, and long-term stability. The process is tunable and
      flexible because it relies on the control of mixing and aggregation timescales.
      It is anticipated that the technique can be applied to a variety of hydrophobic
      active compounds, fluorescent dyes, and inorganic nanostructures, yielding CNPs
      for combined therapy and multimodal imaging applications.

PMID- 18044946
TI  - DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells.
AB  - Carbon nanotubes (CNTs) have shown promise as an important new class of
      multifunctional building blocks and innovative tools in a large variety of
      applications, ranging from nanocomposite materials through nanoelectronics to
      biomedical devices. Because of their unusual one-dimensional hollow nanostructure
      and unique physicochemical properties, CNTs are particularly useful as novel drug
      delivery tools and imaging agents. However, such biomedical applications will not
      be realized if there is no proper assessment of the potential hazards of CNTs to
      humans and other biological systems. Although a few reports on the cytotoxicity
      of CNTs have been published, very little is known about the toxicity at the
      molecular level, or genotoxicity, of CNTs in mammalian cells. We have for the
      first time assessed the DNA damage response to multiwalled carbon nanotubes
      (MWNTs) in mouse embryonic stem (ES) cells. We found that MWNTs can accumulate
      and induce apoptosis in mouse ES cells and activate the tumor suppressor protein
      p53 within 2 h of exposure. Furthermore, we also observed increased expression of
      two isoforms of base excision repair protein 8-oxoguanine-DNA glycosylase 1
      (OGG1), double strand break repair protein Rad 51, phosphorylation of H2AX
      histone at serine 139, and SUMO modification of XRCC4 following the treatment
      with MWNTs. A mutagenesis study using an endogenous molecular marker, adenine
      phosphoribosyltransferase (Aprt), showed that MWNTs increased the mutation
      frequency by 2-fold compared with the spontaneous mutation frequency in mouse ES
      cells. These results suggest that careful scrutiny of the genotoxicity of
      nanomaterials is needed even for those materials, like multiwalled carbon
      nanotubes, that have been previously demonstrated to have limited or no toxicity
      at the cellular level.

PMID- 18044947
TI  - DNA nanopositioning and alignment by electron-beam-induced surface chemical
      patterning.
AB  - Nanopositioning and alignment of arrays of DNA molecules on a surface by
      combination of high-resolution prepatterning and standard macroscopic deposition
      is presented. Direct electron beam exposure of a graphite substrate activated by
      amino groups neutralizes locally the surface charge, preventing the DNA adhesion
      during the consequent deposition. Because of the high resolution of the electron
      beam writing process, precise active patches can be created directly on the
      functionalized surface. Narrow (50 nm) stripe patterns produce both positioning
      and alignment acting as electrostatic traps for the DNA molecules. The approach
      is demonstrated using triple- and double-stranded DNA of medium length (350 nm).
      High yield of alignment and regular arrangement of the deposited molecules are
      achieved in a simple way within large areas.

PMID- 18044948
TI  - Theoretical study of radical and neutral intermediates of artemisinin
      decomposition.
AB  - Four artemisinin reductive decomposition routes A, B1, B2, and B3 with 13 species
      (QHS, 1/2, 3, 4, 5, 5a, 6, 7, 18, 18a, 19, 20, and 21) were studied at the
      B3LYP/6-31G** level. Structures of the species were analyzed in terms of
      geometrical parameters, Lowdin bond orders, partial atomic charges and spin
      densities, electronic and free energies, and entropy. Searches in the Cambridge
      Structural Database for high-level quality artemisinin-related structures were
      also performed. Principal Component and Hierarchical Cluster analyses were
      performed on selected electronic and structural variables to rationalize
      relationships between the routes. The A and B1 routes are possibly
      interconnected. Structural and electronic features of all species show that there
      are two clusters: A-B1 and B2-B3. The latter cluster is thermodynamically more
      favorable (DeltaDeltaG is -64 to -88 kcal mol(-1)) than the former (DeltaDeltaG
      is -58 to -59 kcal mol(-1)), but kinetical preference may be the opposite. Along
      the artemisinin decomposition routes, especially B2 and B3, larger structural
      changes including formation of branched structures and CO2 release are related to
      increased exothermicity of the conversions, weakened attractive oxygen-oxygen
      interactions, and increased entropy of the formed species. The intermediate 4
      definitely belongs to some minor artemisinin decomposition route.

PMID- 18044949
TI  - Similarity based docking.
AB  - We have recently introduced GMA, a highly efficient method for flexible molecular
      alignment. Here we show how this approach can be used to improve docking accuracy
      and efficiency, in cases where a complex structure of a ligand with the target
      protein is known. In cases where a known ligand exists, yet the complex structure
      is unknown it is possible to make use of the advantages offered by this approach,
      by combining it with standard ligand docking.

PMID- 18044950
TI  - New serotonin 5-HT(6) ligands from common feature pharmacophore hypotheses.
AB  - Serotonin 5-HT6 receptor antagonists are thought to play an important role in the
      treatment of psychiatry, Alzheimer's disease, and probably obesity. To find novel
      and potent 5-HT6 antagonists and to provide a new idea for drug design, we used a
      ligand-based pharmacophore to perform the virtual screening of a commercially
      available database. A three-dimensional common feature pharmacophore model was
      developed by using the HipHop program provided in Catalyst software and was used
      as a query for screening the database. A recursive partitioning (RP) model which
      can separate active and inactive compounds was used as a filtering system.
      Finally a sequential virtual screening procedure (SQSP) was conducted, wherein
      both the common feature pharmacophore and the RP model were used in succession to
      improve the results. Some of the hits were selected based on druglikeness, ADME
      properties, structural diversity, and synthetic accessibility for real biological
      evaluation. The best hit compound showed a significant IC50 value of 9.6 nM and
      can be used as a lead for further drug development.

PMID- 18044951
TI  - A pyrazolate-supported Fe(3)(mu(3)-O) core: structural, spectroscopic,
      electrochemical, and magnetic study.
AB  - A comparison is made between the structural, spectroscopic, electrochemical, and
      magnetic properties of pyrazolate versus carboxylate complexes [Fe3(mu3(mu3O)(mu
      LL)6Cl3]2- containing the Fe3(mu3-O)-motif. While the Fe3(mu3-O)-cores are
      structurally indistinguishable in the two types of complexes, their magnetic
      properties deviate from the expected values as a result of a through-pyrazole
      contribution to the overall antiferromagnetic exchange with J1/hc = -80.1 cm(-1)
      and J2/hc = -72.4 cm(-1), or J1/hc = 70.6 cm(-1) and J2/hc = -80.8 cm(-1), (Hex =
      -J1(S1S2 + S2S3) - J2S1S3). The magnetic properties of the pyrazolate complexes
      are further tuned by an antisymmetric exchange interaction term.

PMID- 18044952
TI  - Synthesis of pendant-type anthraquinone-bridged cofacial dinuclear platinum(II)
      complexes and their emission properties.
AB  - Anthraquinone-bridged mononuclear and dinuclear complexes, [PtCl(AQ-amide
      tpy)](PF6) (1), [Pt2Cl2(AQ-amide-tpy2)](PF6)2 (2), and [Pt2Cl2(AQ-eth
      tpy2)](PF6)2 (3), were synthesized and their photochemical properties were
      investigated. Amide-bound mononuclear complex 1 exhibited only metal-to-ligand
      charge transfer (MLCT) absorption and emission, whereas dinuclear complex 2
      exhibited a low-energy emission around 700 nm at room temperature. Emission
      lifetime analysis indicated that this emission was originated from the metal
      metal-to-ligand charge transfer (MMLCT) excited state, implying the existence of
      an intramolecular Pt-Pt interaction at the photoexcited state. 3 with rigid
      ethynylene linkers showed a low-energy absorption around 520 nm (epsilon =
      approximately 1100 M(-1) cm(-1)) in addition to an 1MLCT absorption, which was
      ascribed to a 3MLCT absorption from the consideration of the Pt-Pt distance on a
      geometry-optimized structure. The emission of 3 appeared at 600 nm, which is
      higher in energy compared with the emission of 2. It is postulated that the
      restriction of the Pt-Pt distance flexibility in the rigid structure of 3
      prevents the significant increase of the Pt-Pt interaction at the excited state.

PMID- 18044953
TI  - Synthesis, crystal structures, and photophysical properties of homodinuclear
      lanthanide xanthene-9-carboxylates.
AB  - Three new homodinuclear lanthanide(III) complexes of xanthene-9-carboxylic acid,
      [Ln2(XA)6(DMSO)2(H2O)2](Ln = Eu (1), Tb (2) and Gd (3); HXA = xanthene-9
      carboxylic acid; DMSO = dimethylsulfoxide), have been synthesized, of which 1 and
      2 were structurally characterized by single-crystal X-ray diffraction. These
      compounds crystallize in the monoclinic space group P21/n with a =17.849(4) A, b
      = 9.6537(19) A, c = 23.127(5) A, beta = 109.06(3) degrees , and V = 3766.5(13) A3
      for 1 and a =17.809(4) A, b = 9.6548(19) A, c = 23.075(5) A, beta = 108.97(3)
      degrees , and V = 3752.1(13) A3 for 2. The crystal structures of 1 and 2 consist
      of homodinuclear species that are bridged by two oxygen atoms from two
      carboxylate ligands. The two lanthanide ions are related by a center of
      inversion. Each lanthanide ion is coordinated by eight oxygen atoms in an overall
      distorted square-prismatic geometry. Six of the oxygen atoms are furnished by the
      carboxylate moieties, and the remaining two oxygen atoms are provided by water
      and DMSO molecules. The photophysical properties of these complexes in the solid
      state at room temperature have been investigated. The quantum yields were found
      to be 0.06 +/- 0.01 and 7.30 +/- 0.73% for 1 and 2, respectively.

PMID- 18044954
TI  - Selective phosphorescence chemosensor for homocysteine based on an iridium(III)
      complex.
AB  - A new homocysteine-selective sensor based on the iridium(III) complex
      Ir(pba)2(acac) (Hpba = 4-(2-pyridyl)benzaldehyde; acac = acetylacetone) was
      synthesized, and its' photophysical properties were studied. Upon the addition of
      homocysteine (Hcy) to a semi-aqueous solution of Ir(pba)2(acac), a color change
      from orange to yellow and a luminescent variation from deep red to green were
      evident to the naked eye. The blue-shift of the absorption spectrum and
      enhancement of the phosphorescence emission upon the addition of Hcy can be
      attributed to the formation of a thiazinane group by selective reaction of the
      aldehyde group of Ir(pba)2(acac) with Hcy, which was confirmed by 1H NMR studies.
      Importantly, Ir(pba)2(acac) shows uniquely luminescent recognition of Hcy over
      other amino acids (including cysteine) and thiol-related peptides (reduced
      glutathione), in agreement with the higher luminescent quantum yield of the
      adduct of Ir(pba)2(acac) with Hcy (0.038) compared with that of the adduct with
      Cys (~0.002). Both surface charge analysis and the electrochemical measurement
      indicated that a photoinduced electron-transfer process for Ir(pba)2(acac)-Cys
      might be responsible for the high specificity of Ir(pba)2(acac) toward Hcy over
      Cys.

PMID- 18044955
TI  - Silylation, sulfidation, and benzene-1,2-dithiolate complexation reactions of oxo
      and oxosulfidomolybdates(VI) and -tungstates(VI).
AB  - The synthesis and structures of two types of molecules are presented: [MVIO3 -
      nSn(OSiR2R')]1- (M = Mo, n = 0-3; M = W, n = 3) and [MVIO2(OSiR2R')(bdt)]1- (M =
      Mo, W; bdt = benzene-1,2-dithiolate). For both types, R2R' are Me3, Pri3, Ph3,
      Me2But and Ph2But. The complete series of oxo/sulfido/silyloxo molybdenum
      complexes has been prepared. Complexes with n = 0 are readily prepared by the
      silylation of Ag2MoO4 and sustain mono- or disulfidation with Ph3SiSH to form a
      species with n = 1 and n = 2, respectively. Complexes with n = 3 are accessible
      by the silylation of [MOS3]2-. Structures of the representative series members
      [MoO3(OSiPh2But)]1-, [MoO2S(OSiPh3)]1-, [MoOS2(OSiPri3)]1-, [MoS3(OSiPh2But)]1-,
      and also [WS3(OSiMe2But)]1-, all with tetrahedral stereochemistry, are presented.
      Benzene-1,2-dithiolate complexes are prepared by the reaction of [MoO3(OSiR2R')]1
      with the dithiol or by the silylation of previously reported [MO3(bdt)]2-. The
      structures of [MoO2(OSiPh2But)(bdt)]1- and [WO2(OSiPri3)(bdt)]1- conform to
      square-pyramidal stereochemistry with an oxo ligand in the apical position. The
      role of these complexes in the preparation of site analogues of the xanthine
      oxidoreductase enzyme family is noted. The sulfidation reactions reported here
      point to the utility of Ph3SiSH and Pri3SiSH as reagents for MoVI-based oxo-for
      sulfido conversions.

PMID- 18044956
TI  - Valence bond approach of metal-ligand bonding in the Dewar-Chatt-Duncanson model.
AB  - Metal-ligand bonding, as considered in the Dewar-Chatt-Duncanson model, is
      described via an ab initio Valence Bond (VB) approach and applied to typical Pd-L
      complexes (L = NH3, PH3, CH2, SiH2). A progressive construction of the VB wave
      function is followed and leads to a very compact, though accurate, description of
      metal-ligand bonds. A description with the donation interaction only (ligand
      metal) is first constructed and enriched so the back-donation interactions (metal
      ligand) are also introduced. This latter VB wave function, although being
      extremely compact, provides bonding energies in agreement with standard
      (correlated) methods. A comparison between the two VB levels allows a
      quantification of adiabatic back-bonding energies and reveals very different
      trends between the ligands considered. A very faint back-donation in Pd-NH3 is
      found, which contrasts with a significant effect in Pd-PH3. Back-donation is,
      however, more important in Pd-XH2 complexes. In Pd-CH2, it is such that it even
      represents the major source of bonding. For Pd-SiH2, back-donation is slightly
      weaker than donation. The nature of the interaction in these metal-ligand
      complexes is revealed by the VB wave function analysis. Results are as well
      rationalized using the simple molecular orbital picture and compared to previous
      studies.

PMID- 18044957
TI  - Validation and application of a method for the determination of buprenorphine,
      norbuprenorphine, and their glucuronide conjugates in human meconium.
AB  - A novel liquid chromatography tandem mass spectrometry method for quantification
      of buprenorphine, norbuprenorphine, and glucuronidated conjugates was developed
      and validated. Analytes were extracted from meconium using buffer, concentrated
      by solid-phase extraction and quantified within 13.5 min. In order to determine
      free and total concentrations, specimens were analyzed with and without enzyme
      hydrolysis. Calibration was achieved by linear regression with a 1/x weighting
      factor and deuterated internal standards. All analytes were linear from 20 to
      2000 ng/g with a correlation of determination of >0.98. Accuracy was >or=85.7%
      with intra-assay and interassay imprecision<or=13.9 and 12.4%, respectively.
      There was no interference from 70 licit and illicit drugs and metabolites. Buffer
      extraction followed by SPE yielded recoveries of >or=85.0%. There was suppression
      of ionization by the polar matrix; however, this did not interfere with
      sensitivity or analyte quantification due to inclusion of deuterated internal
      standards. Analytes were stable on the autosampler, at room temperature, at 4
      degrees C, and when exposed to three freeze/thaw cycles. This sensitive and
      specific method can be used to monitor in utero buprenorphine exposure and to
      evaluate correlations, if any, between buprenorphine exposure and neonatal
      outcomes.

PMID- 18044958
TI  - Capillary-based multi nanoelectrospray emitters: improvements in ion transmission
      efficiency and implementation with capillary reversed-phase LC-ESI-MS.
AB  - We describe the coupling of liquid chromatography (LC) separations with mass
      spectrometry (MS) using nanoelectrospray ionization (nano-ESI) multiemitters. The
      array of 19 emitters reduced the flow rate delivered to each emitter, allowing
      the enhanced sensitivity that is characteristic of nano-ESI to be extended to
      higher flow rate separations. The signal for tryptic fragments from proteins
      spiked into a human plasma sample increased 11-fold on average when the
      multiemitters were employed, due to increased ionization efficiency and improved
      ion transfer efficiency through a newly designed heated multicapillary MS inlet.
      Additionally, the LC peak signal-to-noise ratio increased approximately 7-fold
      when the multiemitter configuration was used. The low dead volume of the emitter
      arrays preserved peak shape and resolution for robust capillary LC separations
      using total flow rates of 2 microL/min.

PMID- 18044959
TI  - Conjugated polyelectrolyte based real-time fluorescence assay for phospholipase
      C.
AB  - A fluorescence turnoff assay for phospholipase C (PLC) from Clostridium
      perfringens is developed based on the reversible interaction between the natural
      substrate, phosphatidylcholine, and a fluorescent, water-soluble conjugated
      polyelectrolyte (CPE). The fluorescence intensity of the CPE in water is
      increased substantially by the addition of the phospholipid due to the formation
      of a CPE-lipid complex. Incubation of the CPE-lipid complex with the enzyme PLC
      causes the fluorescence intensity to decrease (turnoff sensor); the response
      arises due to PLC-catalyzed hydrolysis of the phosphatidylcholine, which
      effectively disrupts the CPE-lipid complex. The PLC assay operates with
      phospholipid substrate concentrations in the micromolar range, and the analytical
      detection limit for PLC is <1 nM. The optimized assay provides a convenient,
      rapid, and real-time sensor for PLC activity. The real-time fluorescence
      intensity from the CPE can be converted to substrate concentration by using an ex
      situ calibration curve, allowing PLC-catalyzed reaction rates and kinetic
      parameters to be determined. PLC activation by Ca2+ and inhibition by EDTA and
      fluoride ion are demonstrated using the optimized sensor.

PMID- 18044961
TI  - Analysis and quantitation of fructooligosaccharides using matrix-assisted laser
      desorption/ionization Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - Inulin is a class of fructooligosaccharide (FOS) derived from plants, which is
      often used as a natural food ingredient. Inulin is currently used as an additive
      in baked goods, dairy products, infant formula, and dietary supplements as a
      result of its purported health-promoting properties. The growth of health
      promoting lactobacilli and bifidobacteria is supported by FOS, giving it the
      classification of a prebiotic; however, its ability to selectivity stimulate only
      beneficial bacteria has not been demonstrated. In order to better understand the
      role of inulin and FOS as prebiotics, matrix-assisted laser desorption/ionization
      Fourier transform ion cyclotron resonance mass spectrometry has been used for
      qualitative and quantitative analysis on bacterial growth. A method using an
      internal standard has been developed to quantify the consumption of FOS by
      Bifidobacterium longum bv. infantis using a calibration curve. Due to the
      differential consumption of FOS, the calibration curve was modified to include
      intensity components for each polymer unit in order to achieve more accurate
      quantitation. The method described was designed to be more rapid, precise, and
      robust for quantitative analysis when compared to existing methods.

PMID- 18044960
TI  - Fully automated four-column capillary LC-MS system for maximizing throughput in
      proteomic analyses.
AB  - We describe a four-column, high-pressure capillary liquid chromatography (LC)
      system for robust, high-throughput liquid chromatography-mass spectrometry (LC
      MS(/MS)) analyses. This system performs multiple LC separations in parallel, but
      staggers each of them such that the data-rich region of each separation is
      sampled sequentially. By allowing nearly continuous data acquisition, this design
      maximizes the use of the mass spectrometer. Each analytical column is connected
      to a corresponding ESI emitter in order to avoid the use of postcolumn switching
      and associated dead volume issues. Encoding translation stages are employed to
      sequentially position the emitters at the MS inlet. The high reproducibility of
      this system is demonstrated using consecutive analyses of global tryptic digest
      of the microbe Shewanella oneidensis.

PMID- 18044962
TI  - Counterflow rejection of adsorbing proteins for characterization of biomolecular
      interactions by temperature gradient focusing.
AB  - A new technique is described for the analysis of small molecules in samples
      containing serum proteins and for the measurement of the binding of small
      molecules to serum proteins. The new technique is based on temperature gradient
      focusing (TGF) and takes advantage of the counterflow used with TGF to exclude
      serum proteins from the analysis channel while small molecules are focused for
      detection. The technique is demonstrated for the measurement of the binding
      constant between a small molecule and serum albumin using both a direct
      measurement of the free fraction of the small molecule as well as using a
      competitive binding assay.

PMID- 18044963
TI  - Characterization of the aggregation-prevention activity of p97/valosin-containing
      protein.
AB  - The 97 kDa valosin-containing protein (VCP) belongs to a highly conserved AAA
      (ATPases associated with a variety of activities) family and contains two ATPase
      domains, D1 and D2. VCP participates in numerous cellular activities, such as
      membrane fusion, postmitotic Golgi reassembly, endoplasmic reticulum-associated
      degradation, ubiquitin-proteasome-mediated proteolysis, and many others. In
      performing these activities, VCP presumably acts as a molecular chaperone that
      prevents protein aggregation and modifies protein conformation. In this study, we
      characterized the aggregation-prevention activity of VCP and identified the
      structural requirement for this activity. We used multiple methods to treat
      aggregation-prone luciferase (Luc) and showed that VCP prevents the aggregation
      of Luc in vitro. These results are in agreement; in vivo RNA interference
      analyses showed that a reduction of VCP level results in more aggregation of Luc
      in cells. Structural and functional analyses further demonstrated that the D1
      domain of VCP is sufficient to mediate the aggregation-prevention activity, which
      does not require ATP binding, ATP hydrolysis, or a hexameric structure of VCP.
      Together, these results indicate that (1) VCP prevents protein aggregation in
      vitro and in vivo, (2) this aggregation-prevention activity is mediated mainly
      through the D1 domain of VCP, and (3) this activity does not require ATPase
      activity or a hexameric structure of VCP.

PMID- 18044964
TI  - Functional implications for a prototypical K-turn binding protein from structural
      and dynamical studies of 15.5K.
AB  - The kink-turn (K-turn) motif is recognized and bound by a family of proteins that
      act as nucleation factors for ribonucleoparticle assembly. The binding of various
      proteins to a conserved RNA structural motif known as the K-turn has been shown
      to be an important component of regulation in the ribosome, in the spliceosome,
      and in RNA modification. 15.5K is a prototypical example of a K-turn binding
      protein, which has been shown to bind the 5'-U4 stem-loop of the spliceosome and
      the box C/D motif. We describe the solution NMR structure of free 15.5K, as well
      as studies of conformational flexibility from 15N NMR relaxation and H/D exchange
      experiments. The protein appears well-structured aside from conformational
      fluctuation in alpha3. Flexibility in fast time scale motions and the observation
      of limited intermediate and slow motions further characterize the free protein
      and may suggest local contributions to recognition and binding.

PMID- 18044965
TI  - Myristoyl-based transport of peptides into living cells.
AB  - Translocation of membrane-impermeant molecules to the interior of living cells is
      a necessity for many biochemical investigations. Myristoylation was studied as a
      means to introduce peptides into living cells. Uptake of a myristoylated,
      fluorescent peptide was efficient in the B lymphocyte cell line BA/F3. In
      contrast, this cell line was resistant to uptake of a cell-penetrating peptide
      derived from the TAT protein. In BA/F3 cells, membrane association was shown to
      be rapid, reaching a maximum within 30 min. Cellular uptake of the peptide lagged
      the membrane association but occurred within a similar time frame. Experiments
      performed at 37 versus 4 degrees C demonstrated profound temperature dependence
      in the cellular uptake of myristoylated cargo. Myristoylated peptides with either
      positive or negative charge were shown to load efficiently. In contrast to TAT
      conjugated cargo, pyrenebutyrate did not enhance cellular uptake of the
      myristoylated peptide. The myristoylated peptide did not adversely affect cell
      viability at concentrations up to 100 muM. This assessment of myristoyl-based
      transport provides fundamental data needed in understanding the intracellular
      delivery of myristoylated peptide cargoes for cell-based biochemical studies.

PMID- 18044966
TI  - CGFS-type monothiol glutaredoxins from the cyanobacterium Synechocystis PCC6803
      and other evolutionary distant model organisms possess a glutathione-ligated [2Fe
      2S] cluster.
AB  - When produced in Escherichia coli, the CGFS-type monothiol Grxs from this
      organism (EcGrx4p) and the model cyanobacterium Synechocystis (SyGrx3p) exist as
      a dimeric iron-sulfur containing holoprotein or as a monomeric apoprotein in
      solution. Spectroscopic and site-directed mutagenesis analyses show that the
      SyGrx3 holoprotein contains a subunit-bridging [2Fe-2S] cluster that is ligated
      by the catalytic cysteine located in the CGFS motif of each monomer and the
      cysteines of two molecules of glutathione. The biochemical characterization of
      several monothiol Grxs from the cyanobacteria Gloeobacter violaceus (GvGrx3p) and
      Thermosynechococcus elongatus (TeGrx3p), the yeast Saccharomyces cerevisiae
      (ScGrx3p, ScGrx4p, and ScGrx5p), the plant Arabidopsis thaliana (AtGrx5p), and
      human (HsGrx5p) indicate that the incorporation of a GSH-ligated [2Fe-2S] center
      is a common feature of prokaryotic and eukaryotic CGFS-active site monothiol
      Grxs. In light of these results, the involvement of these enzymes in the sensing
      of iron and/or the biogenesis and transfer of Fe-S cluster is discussed.

PMID- 18044967
TI  - Laminin-induced activation of Rac1 and JNKp46 is initiated by Src family kinases
      and mimics the effects of skeletal muscle contraction.
AB  - Binding of laminin to dystroglycan in the dystrophin glycoprotein complex causes
      signaling through dystroglycan-syntrophin-grb2-SOS1-Rac1-PAK1-JNK. Laminin
      binding also causes syntrophin tyrosine phosphorylation to initiate signaling.
      The kinase responsible was investigated here. PP2 and SU6656, specific inhibitors
      of Src family kinases, decreased the amount of phosphotyrosine syntrophin and
      decreased the level of active Rac1 in laminin-treated myoblasts, myotubes, or
      skeletal muscle microsomes. c-Src and c-Fyn both phosphorylate syntrophin, and
      inhibition of either with specific siRNAs diminishes the level of syntrophin
      phosphorylation. When the rat gastrocnemius was contracted, the level of Rac1
      activation increased compared to that of the relaxed control muscle and Rac1
      colocalized with beta-dystroglycan. Similar results were obtained when the muscle
      was stretched. Contracted muscle also contained more activated c-Jun N-terminal
      kinase, JNKp46. E3, an expressed protein containing only laminin domains LG4 and
      LG5, increased the rate of proliferation of myoblasts, and PP2 prevented cell
      proliferation. In addition, Src family kinases colocalized with activated Rac1
      and with laminin-Sepharose in solid-phase binding assays. Thus, contraction,
      stretching, or laminin binding causes recruitment of Src family kinase to the
      dystrophin glycoprotein complex, activating Rac1 and inducing downstream
      signaling. The DGC likely represents a mechanoreceptor in skeletal muscle
      regulating muscle growth in response to muscle activity. Src family kinases play
      an initiating and critical role.

PMID- 18044968
TI  - Structural and kinetic study of differences between human and Escherichia coli
      manganese superoxide dismutases.
AB  - Human manganese superoxide dismutase (MnSOD) is characterized by a product
      inhibition stronger than that observed in bacterial forms of MnSOD. Previous
      studies show that the conserved, active-site residue Tyr34 mediates product
      inhibition; however, the protein environment of Tyr34 is different in human and
      Escherichia coli MnSOD. We have prepared two site-specific mutants of human MnSOD
      with replacements of Phe66 with Ala and Leu (F66A and F66L, respectively),
      altering the surroundings of Tyr34. Pulse radiolysis was used to generate
      superoxide, and measurements of catalysis were taken in single-turnover
      experiments by observing the visible absorbance of species of MnSOD and under
      catalytic conditions observing the absorbance of superoxide. The mutation of
      Phe66 to Leu resulted in a mutant of human MnSOD with weakened product inhibition
      resembling that of E. coli MnSOD. Moreover, the mechanism of this weakened
      product inhibition was similar to that in E. coli MnSOD, specifically a decrease
      in the rate constant for the oxidative addition of superoxide to Mn2+MnSOD
      leading to the formation of the peroxide-inhibited enzyme. In addition, the
      crystal structures of both mutants have been determined and compared to those of
      wild-type human and E. coli MnSOD. The crystallographic data suggest that the
      solvent structure and its mobility as well as side chain conformations may affect
      the extent of product inhibition. These data emphasize the role of residue 66 in
      catalysis and inhibition and provide a structural explanation for differences in
      catalytic properties between human and certain bacterial forms of MnSOD.

PMID- 18044969
TI  - Histone lysine methyltransferase SET7/9: formation of a water channel precedes
      each methyl transfer.
AB  - Molecular dynamics (MD) simulations and hybrid quantum mechanics/molecular
      mechanics (QM/MM) calculations have been carried out in an investigation of
      histone lysine methyltransferase (SET7/9). Proton dissociation (SET7/9.Lys4
      NH3+.AdoMet --> SET7/9.Lys4-NH2.AdoMet + H+) must be prior to the methylation by
      S-adenosylmethionine (AdoMet). We find that a water channel is formed to allow
      escape of the proton to solvent. The water channel appears in the presence of
      AdoMet, but is not present in the species SET7/9.Lys4-NH3+ or SET7/9.Lys4
      N(Me)H2+.AdoHcy. A water channel is not formed in the ground state of SET7/9.Lys4
      N(Me)H2+.AdoMet, and the second methyl transfer does not occur. The structure of
      SET7/9.Lys4-N(Me)H2+.AdoMet includes a greater distance (6.1 +/- 0.3 A) between
      Cgamma(AdoMet) and N(MeLys4) than is present in SET7/9.Lys4-NH3+.AdoMet (5.7 +/-
      0.2 A). The electrostatic interactions between the positive charges on AdoMet and
      SET7/9.Lys4-NH3+ decrease the pKa of the latter from 10.9 +/- 0.4 to 8.2 +/- 0.6,
      and this is not seen in the SET7/9.Lys4-N(Me)H2+.AdoMet species. The formation,
      or not, of a water channel, the distance between Sdelta(AdoMet) and N(Lys4), and
      the angle Sdelta(AdoMet)-Cgamma(AdoMet)-N(Lys4) determine whether methyl transfer
      can occur. By QM/MM, the calculated free energy barrier of the methyl transfer
      reaction in the SET7/9 [Lys4-NH2 + AdoMet --> Lys4-N(Me)H2+ + AdoHcy] complex is
      DeltaG++ = 19.0 +/- 1.6 kcal/mol. This DeltaG++ is in agreement with the value of
      20.9 kcal/mol calculated from the experimental rate constant (0.24 min(-1)).

PMID- 18044970
TI  - Heme synthase (ferrochelatase) catalyzes the removal of iron from heme and
      demetalation of metalloporphyrins.
AB  - The red pigments in meat products, including cooked cured ham, arise from the
      reaction of myoglobin with nitric oxide generated from exogenous nitrite. Since
      carcinogenic nitrosoamines may be generated by the treatment of meats with
      nitrite, the production of nitrite-free meat products is an attractive
      alternative. Raw dry-cured (Parma) hams are produced by the treatment of meats
      with salts other than nitrite. Analysis of pigments in raw dry-cured hams reveals
      that the main pigment is zinc protoporphyrin, suggesting that the conversion of
      heme to zinc protoporphyrin occurs via an iron-removal reaction from myoglobin
      heme during the processing of raw hams. Purification of the iron-removal enzyme
      showed that it was identical to ferrochelatase. Recombinant ferrochelatase in
      combination with NADH-cytochrome b5 reductase catalyzed NADH-dependent iron
      removal reaction from hemin and hemoproteins. Metal ions such as zinc and cobalt
      were also removed from the corresponding metalloporphyrins. The addition of zinc
      ions led to the formation of zinc protoporphyrin. In cultured cells, the
      conversion of zinc mesoporphyrin to mesoheme was observed to be dependent on
      ferrochelatase and could be markedly induced during erythroid differentiation.
      This is the first demonstration of a new enzyme reaction, the reverse reaction of
      ferrochelatase, which may contribute to a new route of the recycling of
      protoporphyrin and heme in cells.

PMID- 18044972
TI  - DNA conformational effects on the interaction of netropsin with A-tract
      sequences.
AB  - The influence of cosolutes and DNA sequence on the interaction of netropsin with
      three duplexes has been studied by isothermal titration calorimetry. In buffer,
      netropsin forms two complexes with a net stoichiometry of 1:1 in the minor groove
      of the oligonucleotide (GCGCGAATTCGCGC)2. One complex has a weaker affinity and
      is more enthalpically favored relative to the other one, consistent with previous
      studies [Freyer, M. W., et al. (2006) Biophys. Chem. 126, 186-196]. With the
      cosolutes betaine and 2-methyl-2,4-pentanediol, the enthalpy and heat capacity
      changes indicate that the complex with weaker affinity is disfavored relative to
      the complex with higher affinity. With (CGCGCAATTGCGCG)2, netropsin has one
      binding mode in buffer, and complex formation is not influenced by the cosolutes.
      The similarities of the enthalpy and heat capacity changes suggest that netropsin
      interacts similarly with these two oligonucleotides in the presence of cosolutes.
      The oligonucleotide (GCGCAAATTTGCGC)2 also forms two complexes with netropsin,
      and the complex with weaker affinity is again disfavored by the cosolutes. Thus,
      the interaction of netropsin with these A/T binding sites is influenced both by
      the bases adjacent to the binding site and by cosolutes. We suggest that these
      two factors influence the conformation of the minor-groove binding site of DNA.

PMID- 18044971
TI  - Dioxygen activation at non-heme diiron centers: oxidation of a proximal residue
      in the I100W variant of toluene/o-xylene monooxygenase hydroxylase.
AB  - At its carboxylate-bridged diiron active site, the hydroxylase component of
      toluene/o-xylene monooxygenase activates dioxygen for subsequent arene
      hydroxylation. In an I100W variant of this enzyme, we characterized the formation
      and decay of two species formed by addition of dioxygen to the reduced,
      diiron(II) state by rapid-freeze quench (RFQ) EPR, Mossbauer, and ENDOR
      spectroscopy. The dependence of the formation and decay rates of this mixed
      valent transient on pH and the presence of phenol, propylene, or acetylene was
      investigated by double-mixing stopped-flow optical spectroscopy. Modification of
      the alpha-subunit of the hydroxylase after reaction of the reduced protein with
      dioxygen-saturated buffer was investigated by tryptic digestion coupled mass
      spectrometry. From these investigations, we conclude that (i) a diiron(III,IV)-W*
      transient, kinetically linked to a preceding diiron(III) intermediate, arises
      from the one-electron oxidation of W100, (ii) the tryptophan radical is
      deprotonated, (iii) rapid exchange of either a terminal water or hydroxide ion
      with water occurs at the ferric ion in the diiron(III,IV) cluster, and (iv) the
      diiron(III,IV) core and W* decay to the diiron(III) product by a common
      mechanism. No transient radical was observed by stopped-flow optical spectroscopy
      for reactions of the reduced hydroxylase variants I100Y, L208F, and F205W with
      dioxygen. The absence of such species, and the deprotonated state of the
      tryptophanyl radical in the diiron(III,IV)-W* transient, allow for a conservative
      estimate of the reduction potential of the diiron(III) intermediate as lying
      between 1.1 and 1.3 V. We also describe the X-ray crystal structure of the I100W
      variant of ToMOH.

PMID- 18044973
TI  - Effect of 2-fluorohistidine labeling of the anthrax protective antigen on
      stability, pore formation, and translocation.
AB  - The action of anthrax toxin relies in part upon the ability of the protective
      antigen (PA) moiety to form a heptameric pore in the endosomal membrane,
      providing a portal for entry of the enzymic moieties of the toxin into the
      cytosol. Pore formation is dependent on a conformational change in the heptameric
      prepore that occurs in the neutral to mildly acidic pH range, and it has been
      hypothesized that protonation of one or more histidine residues triggers this
      transition. To test this hypothesis, we used biosynthetic methods to incorporate
      the unnatural amino acid analogue 2-fluorohistidine (2-FHis) into PA. 2-FHis is
      isosteric with histidine but resists protonation at physiological pH values due
      to a dramatically reduced side-chain pKa ( approximately 1). We found that 2-FHis
      labeled PA was biologically inactive, as judged by its inability to deliver a
      model intracellular effector, LFN-DTA, to the cytosol of CHO-K1 cells. However,
      whereas 2-FHis blocked a conformational transition in the full-length PA83
      protein in the pH 5-6 range, the pH dependence of prepore-to-pore conversion of
      (PA63)7 was unchanged from the wild-type protein, implying that this conversion
      is not dependent on His protonation. Consistent with this result, the labeled,
      trypsin-activated PA was able to permeabilize liposomes to K+ and retained pore
      forming activity in planar phospholipid bilayers. The pores in planar bilayers
      were incapable, however, of translocating a model ligand in response to a
      transmembrane pH gradient or elevated voltage. The results indicate that
      protonation of residues other than His, presumably Glu and/or Asp side chains,
      triggers pore formation in vitro, but His residues are nonetheless important for
      PA functioning in vivo.

PMID- 18044974
TI  - Ligand binding and inhibition of an oxygen-sensitive soluble guanylate cyclase,
      Gyc-88E, from Drosophila.
AB  - Soluble guanylate cyclase (sGC) uses a ferrous heme cofactor as a receptor for NO
      and once bound activates the enzyme for the conversion of GTP to cGMP. The heme
      cofactor in sGC does not bind oxygen, thereby allowing it to selectively bind NO
      despite a cellular concentration of oxygen (microM) that is much higher than
      signaling concentrations of nitric oxide (nM). The molecular details of this
      ligand discrimination against oxygen have emerged and allowed for predictions
      regarding ligand specificity in the sGC family. The results reported here show
      that Gyc-88E from Drosophila is a hemoprotein that binds oxygen, as well as NO
      and CO. All three ligands form 6-coordinate complexes. Gyc-88E is active as a
      homodimer (5600 +/- 243 nmol min(-1) mg(-1)) and is inhibited by O2, CO, and NO
      (3.2-, 2.9-, and 2-fold, respectively). The Km for GTP was 0.66 +/- 0.15 mM in
      air (273 microM oxygen) and 0.82 +/- 0.15 mM under anaerobic conditions. The Ki
      for oxygen was calculated to be 51 +/- 28 microM. The biochemical properties of
      Gyc-88E are unique for guanylate cyclases and suggest a possible function as an
      oxygen sensor.

PMID- 18044975
TI  - Chromatographically distinguishable heme insertion isoforms of human hemopexin.
AB  - Two spectroscopically distinct, non-interconverting forms of human hemopexin have
      been isolated by immobilized metal ion affinity chromatography and characterized
      spectroscopically. Form alpha (characterized by a bisignate Soret CD spectrum)
      and form beta (Soret CD characterized by a positive Cotton effect) exhibit
      different spectroscopic responses to addition of Zn2+ or Cu2+, yet both forms
      exhibit the same metal ion-induced decrease in Tm for the thermally induced
      release of the heme prosthetic group. Far UV-CD spectra indicate that the two
      isoforms possess essentially identical secondary structures, but their
      differential retention during metal ion affinity chromatography indicates slight
      differences in exposure of His residues on the protein surface. We propose that
      these observations result from the binding of heme in form beta with an
      orientation that differs from the crystallographically observed binding
      orientation for rabbit hemopexin by rotation of the heme prosthetic group by 180
      degrees about the alpha-gamma meso-carbon axis and from interaction of metal ions
      at two separate binding sites.

PMID- 18044976
TI  - Visualization and classification of amyloid beta supramolecular assemblies.
AB  - Deposition of amyloid beta (Abeta) fibrils has been suggested to play a central
      role in Alzheimer's disease. In clarifying the mechanism by which fibrils form
      and moreover in developing new treatments for amyloidosis, direct observation is
      important. Focusing on the interactions with surfaces at the early stages, we
      studied the spontaneous formation of Abeta(1-40) fibrils on quartz slides,
      monitored by total internal reflection fluorescence microscopy combined with
      thioflavin T, an amyloid-specific fluorescence dye. Self-assembly of Abeta(1-40),
      accelerated by a low concentration of sodium dodecyl sulfate, produced various
      remarkable amyloid assemblies. Densely packed spherulitic structures with radial
      fibril growth were typically observed. When the packing of fibrils was coarse,
      extremely long fibrils often protruded from the spherulitic cores. In other
      cases, a large number of wormlike fibrils were formed. Transmission electron
      microscopy and atomic force microscopy revealed relatively short and straight
      fibrillar blocks associated laterally without tight interaction, leading to
      random-walk-like fibril growth. These results suggest that, during spontaneous
      fibrillation, the nucleation occurring in contact with surfaces is easily
      affected by environmental factors, creating various types of nuclei, and hence
      variations in amyloid morphology. A taxonomy of amyloid supramolecular assemblies
      will be useful in clarifying the structure-function relationship of amyloid
      fibrils.

PMID- 18044977
TI  - High throughput screening reveals several new classes of glutamate dehydrogenase
      inhibitors.
AB  - Glutamate dehydrogenase (GDH) has been shown to play a regulatory role in insulin
      secretion by pancreatic beta-cells. The most compelling evidence of this comes
      from features of the hyperinsulism/hyperammonemia (HI/HA) syndrome where a
      dominant mutation causes the loss of inhibition by GTP, and from studies that
      link leucine (and its analogue BCH) activation of GDH to stimulation of insulin
      secretion. This suggests that GDH may represent a new and novel drug target to
      control a variety of insulin disorders. Recently we demonstrated that a subset of
      green tea polyphenols are potent inhibitors of glutamate dehydrogenase in vitro
      and can efficaciously block BCH stimulation of insulin secretion. In these
      current studies, we extend our search for GDH inhibitors using high throughput
      methods to pan through more than 27,000 compounds. A number of known and new
      inhibitors were identified with IC50s in the low micromolar range. These new
      inhibitors were found to act via apparently different mechanisms with some
      inhibiting the reaction in a positively cooperative manner, the inhibition by
      only some of the compounds was reversed by ADP, and one compound was found to
      stabilize the enzyme against thermal denaturation. Therefore, these new compounds
      not only are new leads in the treatment of hyperactive GDH but also are useful in
      dissecting the complex allosteric nature of the enzyme.

PMID- 18044978
TI  - Sulfur X-ray absorption spectroscopy of living mammalian cells: an enabling tool
      for sulfur metabolomics. In situ observation of uptake of taurine into MDCK
      cells.
AB  - Sulfur is essential for life, with important roles in biological structure and
      function. However, because of a lack of suitable biophysical techniques, in situ
      information about sulfur biochemistry is generally difficult to obtain. Here, we
      present an in situ sulfur X-ray absorption spectroscopy (S-XAS) study of living
      cell cultures of the mammalian renal epithelial MDCK cell line. A great deal of
      information is retrieved from a characteristic sulfonate feature in the X-ray
      absorption spectrum of the cell cultures, which can be related to the amino acid
      taurine. We followed the time and dose dependence of uptake of taurine into MDCK
      cell monolayers. The corresponding uptake curves showed a typical saturation
      behavior with considerable levels of taurine accumulation inside the cells (as
      much as 40% of total cellular sulfur). We also investigated the polarity of
      uptake of taurine into MDCK cells, and our results confirmed that uptake in situ
      is predominantly a function of the basolateral cell surface.

PMID- 18044979
TI  - What are the benefits and risks of fitting patients with radiofrequency
      identification devices.
AB  - BACKGROUND TO THE DEBATE: In 2004, the United States Food and Drug Administration
      approved a radiofrequency identification (RFID) device that is implanted under
      the skin of the upper arm of patients and that stores the patient's medical
      identifier. When a scanner is passed over the device, the identifier is displayed
      on the screen of an RFID reader. An authorized health professional can then use
      the identifier to access the patient's clinical information, which is stored in a
      separate, secure database. Such RFID devices may have many medical benefits--such
      as expediting identification of patients and retrieval of their medical records.
      But critics of the technology have raised several concerns, including the risk of
      the patient's identifying information being used for nonmedical purposes.

PMID- 18044980
TI  - Clinical trials and medical care: defining the therapeutic misconception.

PMID- 18044982
TI  - Vaccines for cholera control: does herd immunity play a role.

PMID- 18044981
TI  - An LRP5 receptor with internal deletion in hyperparathyroid tumors with
      implications for deregulated WNT/beta-catenin signaling.
AB  - BACKGROUND: Hyperparathyroidism (HPT) is a common endocrine disorder with
      incompletely understood etiology, characterized by enlarged hyperactive
      parathyroid glands and increased serum concentrations of parathyroid hormone and
      ionized calcium. We have recently reported activation of the Wnt signaling
      pathway by accumulation of beta-catenin in all analyzed parathyroid tumors from
      patients with primary HPT (pHPT) and in hyperplastic parathyroid glands from
      patients with uremia secondary to HPT (sHPT). Mechanisms that may account for
      this activation have not been identified, except for a few cases of beta-catenin
      (CTNNB1) stabilizing mutation in pHPT tumors. METHODS AND FINDINGS: Reverse
      transcription PCR and Western blot analysis showed expression of an aberrantly
      spliced internally truncated WNT coreceptor low-density lipoprotein receptor
      related protein 5 (LRP5) in 32 out of 37 pHPT tumors (86%) and 20 out of 20 sHPT
      tumors (100%). Stabilizing mutation of CTNNB1 and expression of the internally
      truncated LRP5 receptor was mutually exclusive. Expression of the truncated LRP5
      receptor was required to maintain the nonphosphorylated active beta-catenin
      level, transcription activity of beta-catenin, MYC expression, parathyroid cell
      growth in vitro, and parathyroid tumor growth in a xenograft severe combined
      immunodeficiency (SCID) mouse model. WNT3 ligand and the internally truncated
      LRP5 receptor strongly activated transcription, and the internally truncated LRP5
      receptor was insensitive to inhibition by DKK1. CONCLUSIONS: The internally
      truncated LRP5 receptor is strongly implicated in deregulated activation of the
      WNT/beta-catenin signaling pathway in hyperparathyroid tumors, and presents a
      potential target for therapeutic intervention.

PMID- 18044983
TI  - Controlling endemic cholera with oral vaccines.
AB  - BACKGROUND: Although advances in rehydration therapy have made cholera a
      treatable disease with low case-fatality in settings with appropriate medical
      care, cholera continues to impose considerable mortality in the world's most
      impoverished populations. Internationally licensed, killed whole-cell based oral
      cholera vaccines (OCVs) have been available for over a decade, but have not been
      used for the control of cholera. Recently, these vaccines were shown to confer
      significant levels of herd protection, suggesting that the protective potential
      of these vaccines has been underestimated and that these vaccines may be highly
      effective in cholera control when deployed in mass immunization programs. We used
      a large-scale stochastic simulation model to investigate the possibility of
      controlling endemic cholera with OCVs. METHODS AND FINDINGS: We construct a large
      scale, stochastic cholera transmission model of Matlab, Bangladesh. We find that
      cholera transmission could be controlled in endemic areas with 50% coverage with
      OCVs. At this level of coverage, the model predicts that there would be an 89%
      (95% confidence interval [CI] 72%-98%) reduction in cholera cases among the
      unvaccinated, and a 93% (95% CI 82%-99%) reduction overall in the entire
      population. Even a more modest coverage of 30% would result in a 76% (95% CI 44%
      95%) reduction in cholera incidence for the population area covered. For
      populations that have less natural immunity than the population of Matlab, 70%
      coverage would probably be necessary for cholera control, i.e., an annual
      incidence rate of < or = 1 case per 1,000 people in the population. CONCLUSIONS:
      Endemic cholera could be reduced to an annual incidence rate of < or = 1 case per
      1,000 people in endemic areas with biennial vaccination with OCVs if coverage
      could reach 50%-70% depending on the level of prior immunity in the population.
      These vaccination efforts could be targeted with careful use of ecological data.

PMID- 18044984
TI  - Cholinesterase inhibitors in mild cognitive impairment: a systematic review of
      randomised trials.
AB  - BACKGROUND: Mild cognitive impairment (MCI) refers to a transitional zone between
      normal ageing and dementia. Despite the uncertainty regarding the definition of
      MCI as a clinical entity, clinical trials have been conducted in the attempt to
      study the role of cholinesterase inhibitors (ChEIs) currently approved for
      symptomatic treatment of mild to moderate Alzheimer disease (AD), in preventing
      progression from MCI to AD. The objective of this review is to assess the effects
      of ChEIs (donepezil, rivastigmine, and galantamine) in delaying the conversion
      from MCI to Alzheimer disease or dementia. METHODS AND FINDINGS: The terms
      "donepezil", "rivastigmine", "galantamine", and "mild cognitive impairment" and
      their variants, synonyms, and acronyms were used as search terms in four
      electronic databases (MEDLINE, EMBASE, Cochrane, PsycINFO) and three registers:
      the Cochrane Collaboration Trial Register, Current Controlled Trials, and
      ClinicalTrials.gov. Published and unpublished studies were included if they were
      randomized clinical trials published (or described) in English and conducted
      among persons who had received a diagnosis of MCI and/or abnormal memory function
      documented by a neuropsychological assessment. A standardized data extraction
      form was used. The reporting quality was assessed using the Jadad scale. Three
      published and five unpublished trials met the inclusion criteria (three on
      donepezil, two on rivastigmine, and three on galantamine). Enrolment criteria
      differed among the trials, so the study populations were not homogeneous. The
      duration of the trials ranged from 24 wk to 3 y. No significant differences
      emerged in the probability of conversion from MCI to AD or dementia between the
      treated groups and the placebo groups. The rate of conversion ranged from 13%
      (over 2 y) to 25% (over 3 y) among treated patients, and from 18% (over 2 y) to
      28% (over 3 y) among those in the placebo groups. Only for two studies was it
      possible to derive point estimates of the relative risk of conversion: 0.85 (95%
      confidence interval 0.64-1.12), and 0.84 (0.57-1.25). Statistically significant
      differences emerged for three secondary end points. However, when adjusting for
      multiple comparisons, only one difference remained significant (i.e., the rate of
      atrophy in the whole brain). CONCLUSIONS: The use of ChEIs in MCI was not
      associated with any delay in the onset of AD or dementia. Moreover, the safety
      profile showed that the risks associated with ChEIs are not negligible. The
      uncertainty regarding MCI as a clinical entity raises the question as to the
      scientific validity of these trials.

PMID- 18044985
TI  - How can we draw the line between clinical care and medical research.

PMID- 18044986
TI  - Self-organization in high-density bacterial colonies: efficient crowd control.
AB  - Colonies of bacterial cells can display complex collective dynamics, frequently
      culminating in the formation of biofilms and other ordered super-structures.
      Recent studies suggest that to cope with local environmental challenges,
      bacterial cells can actively seek out small chambers or cavities and assemble
      there, engaging in quorum sensing behavior. By using a novel microfluidic device,
      we showed that within chambers of distinct shapes and sizes allowing continuous
      cell escape, bacterial colonies can gradually self-organize. The directions of
      orientation of cells, their growth, and collective motion are mutually correlated
      and dictated by the chamber walls and locations of chamber exits. The ultimate
      highly organized steady state is conducive to a more-organized escape of cells
      from the chambers and increased access of nutrients into and evacuation of waste
      out of the colonies. Using a computational model, we suggest that the lengths of
      the cells might be optimized to maximize self-organization while minimizing the
      potential for stampede-like exit blockage. The self-organization described here
      may be crucial for the early stage of the organization of high-density bacterial
      colonies populating small, physically confined growth niches. It suggests that
      this phenomenon can play a critical role in bacterial biofilm initiation and
      development of other complex multicellular bacterial super-structures, including
      those implicated in infectious diseases.

PMID- 18044987
TI  - Resolving the fast kinetics of cooperative binding: Ca2+ buffering by calretinin.
AB  - Cooperativity is one of the most important properties of molecular interactions
      in biological systems. It is the ability to influence ligand binding at one site
      of a macromolecule by previous ligand binding at another site of the same
      molecule. As a consequence, the affinity of the macromolecule for the ligand is
      either decreased (negative cooperativity) or increased (positive cooperativity).
      Over the last 100 years, O2 binding to hemoglobin has served as the paradigm for
      cooperative ligand binding and allosteric modulation, and four practical models
      were developed to quantitatively describe the mechanism: the Hill, the Adair
      Klotz, the Monod-Wyman-Changeux, and the Koshland-Nemethy-Filmer models. The
      predictions of these models apply under static conditions when the binding
      reactions are at equilibrium. However, in a physiological setting, e.g., inside a
      cell, the timing and dynamics of the binding events are essential. Hence, it is
      necessary to determine the dynamic properties of cooperative binding to fully
      understand the physiological implications of cooperativity. To date, the Monod
      Wyman-Changeux model was applied to determine the kinetics of cooperative binding
      to biologically active molecules. In this model, cooperativity is established by
      postulating two allosteric isoforms with different binding properties. However,
      these studies were limited to special cases, where transition rates between
      allosteric isoforms are much slower than the binding rates or where binding and
      unbinding rates could be measured independently. For all other cases, the complex
      mathematical description precludes straightforward interpretations. Here, we
      report on calculating for the first time the fast dynamics of a cooperative
      binding process, the binding of Ca2+ to calretinin. Calretinin is a Ca2+-binding
      protein with four cooperative binding sites and one independent binding site. The
      Ca2+ binding to calretinin was assessed by measuring the decay of free Ca2+ using
      a fast fluorescent Ca2+ indicator following rapid (<50-mus rise time) Ca2+
      concentration jumps induced by uncaging Ca2+ from DM-nitrophen. To unravel the
      kinetics of cooperative binding, we devised several approaches based on known
      cooperative binding models, resulting in a novel and relatively simple model.
      This model revealed unexpected and highly specific nonlinear properties of
      cellular Ca2+ regulation by calretinin. The association rate of Ca2+ with
      calretinin speeds up as the free Ca2+ concentration increases from cytoplasmic
      resting conditions ( approximately 100 nM) to approximately 1 muM. As a
      consequence, the Ca2+ buffering speed of calretinin highly depends on the
      prevailing Ca2+ concentration prior to a perturbation. In addition to providing a
      novel mode of action of cellular Ca2+ buffering, our model extends the analysis
      of cooperativity beyond the static steady-state condition, providing a powerful
      tool for the investigation of the dynamics and functional significance of
      cooperative binding in general.

PMID- 18044988
TI  - Mutation of RNA Pol III subunit rpc2/polr3b Leads to Deficiency of Subunit Rpc11
      and disrupts zebrafish digestive development.
AB  - The role of RNA polymerase III (Pol III) in developing vertebrates has not been
      examined. Here, we identify a causative mutation of the second largest Pol III
      subunit, polr3b, that disrupts digestive organ development in zebrafish slim jim
      (slj) mutants. The slj mutation is a splice-site substitution that causes
      deletion of a conserved tract of 41 amino acids in the Polr3b protein. Structural
      considerations predict that the slj Pol3rb deletion might impair its interaction
      with Polr3k, the ortholog of an essential yeast Pol III subunit, Rpc11, which
      promotes RNA cleavage and Pol III recycling. We engineered Schizosaccharomyces
      pombe to carry an Rpc2 deletion comparable to the slj mutation and found that the
      Pol III recovered from this rpc2-delta yeast had markedly reduced levels of
      Rpc11p. Remarkably, overexpression of cDNA encoding the zebrafish rpc11 ortholog,
      polr3k, rescued the exocrine defects in slj mutants, indicating that the slj
      phenotype is due to deficiency of Rpc11. These data show that functional
      interactions between Pol III subunits have been conserved during eukaryotic
      evolution and support the utility of zebrafish as a model vertebrate for analysis
      of Pol III function.

PMID- 18044989
TI  - Light activates output from evening neurons and inhibits output from morning
      neurons in the Drosophila circadian clock.
AB  - Animal circadian clocks are based on multiple oscillators whose interactions
      allow the daily control of complex behaviors. The Drosophila brain contains a
      circadian clock that controls rest-activity rhythms and relies upon different
      groups of PERIOD (PER)-expressing neurons. Two distinct oscillators have been
      functionally characterized under light-dark cycles. Lateral neurons (LNs) that
      express the pigment-dispersing factor (PDF) drive morning activity, whereas PDF
      negative LNs are required for the evening activity. In constant darkness, several
      lines of evidence indicate that the LN morning oscillator (LN-MO) drives the
      activity rhythms, whereas the LN evening oscillator (LN-EO) does not. Since
      mutants devoid of functional CRYPTOCHROME (CRY), as opposed to wild-type flies,
      are rhythmic in constant light, we analyzed transgenic flies expressing PER or
      CRY in the LN-MO or LN-EO. We show that, under constant light conditions and
      reduced CRY function, the LN evening oscillator drives robust activity rhythms,
      whereas the LN morning oscillator does not. Remarkably, light acts by inhibiting
      the LN-MO behavioral output and activating the LN-EO behavioral output. Finally,
      we show that PDF signaling is not required for robust activity rhythms in
      constant light as opposed to its requirement in constant darkness, further
      supporting the minor contribution of the morning cells to the behavior in the
      presence of light. We therefore propose that day-night cycles alternatively
      activate behavioral outputs of the Drosophila evening and morning lateral
      neurons.

PMID- 18044990
TI  - Disruption of state estimation in the human lateral cerebellum.
AB  - The cerebellum has been proposed to be a crucial component in the state
      estimation process that combines information from motor efferent and sensory
      afferent signals to produce a representation of the current state of the motor
      system. Such a state estimate of the moving human arm would be expected to be
      used when the arm is rapidly and skillfully reaching to a target. We now report
      the effects of transcranial magnetic stimulation (TMS) over the ipsilateral
      cerebellum as healthy humans were made to interrupt a slow voluntary movement to
      rapidly reach towards a visually defined target. Errors in the initial direction
      and in the final finger position of this reach-to-target movement were
      significantly higher for cerebellar stimulation than they were in control
      conditions. The average directional errors in the cerebellar TMS condition were
      consistent with the reaching movements being planned and initiated from an
      estimated hand position that was 138 ms out of date. We suggest that these
      results demonstrate that the cerebellum is responsible for estimating the hand
      position over this time interval and that TMS disrupts this state estimate.

PMID- 18044991
TI  - Novel roles of formin mDia2 in lamellipodia and filopodia formation in motile
      cells.
AB  - Actin polymerization-driven protrusion of the leading edge is a key element of
      cell motility. The important actin nucleators formins and the Arp2/3 complex are
      believed to have nonoverlapping functions in inducing actin filament bundles in
      filopodia and dendritic networks in lamellipodia, respectively. We tested this
      idea by investigating the role of mDia2 formin in leading-edge protrusion by loss
      of-function and gain-of-function approaches. Unexpectedly, mDia2 depletion by
      short interfering RNA (siRNA) severely inhibited lamellipodia. Structural
      analysis of the actin network in the few remaining lamellipodia suggested an
      mDia2 role in generation of long filaments. Consistently, constitutively active
      mDia2 (DeltaGBD-mDia2) induced accumulation of long actin filaments in
      lamellipodia and increased persistence of lamellipodial protrusion. Depletion of
      mDia2 also inhibited filopodia, whereas expression of DeltaGBD-mDia2 promoted
      their formation. Correlative light and electron microscopy showed that DeltaGBD
      mDia2-induced filopodia were formed from lamellipodial network through gradual
      convergence of long lamellipodial filaments into bundles. Efficient filopodia
      induction required mDia2 targeting to the membrane, likely through a scaffolding
      protein Abi1. Furthermore, mDia2 and Abi1 interacted through the N-terminal
      regulatory sequences of mDia2 and the SH3-containing Abi1 sequences. We propose
      that mDia2 plays an important role in formation of lamellipodia by nucleating
      and/or protecting from capping lamellipodial actin filaments, which subsequently
      exhibit high tendency to converge into filopodia.

PMID- 18044992
TI  - Draft crystal structure of the vault shell at 9-A resolution.
AB  - Vaults are the largest known cytoplasmic ribonucleoprotein structures and may
      function in innate immunity. The vault shell self-assembles from 96 copies of
      major vault protein and encapsulates two other proteins and a small RNA. We
      crystallized rat liver vaults and several recombinant vaults, all among the
      largest non-icosahedral particles to have been crystallized. The best crystals
      thus far were formed from empty vaults built from a cysteine-tag construct of
      major vault protein (termed cpMVP vaults), diffracting to about 9-A resolution.
      The asymmetric unit contains a half vault of molecular mass 4.65 MDa. X-ray
      phasing was initiated by molecular replacement, using density from cryo-electron
      microscopy (cryo-EM). Phases were improved by density modification, including
      concentric 24- and 48-fold rotational symmetry averaging. From this, the
      continuous cryo-EM electron density separated into domain-like blocks. A draft
      atomic model of cpMVP was fit to this improved density from 15 domain models.
      Three domains were adapted from a nuclear magnetic resonance substructure. Nine
      domain models originated in ab initio tertiary structure prediction. Three C
      terminal domains were built by fitting poly-alanine to the electron density.
      Locations of loops in this model provide sites to test vault functions and to
      exploit vaults as nanocapsules.

PMID- 18044993
TI  - Detection of Hurthle cell carcinoma using sestamibi.

PMID- 18044994
TI  - Application of paclitaxel-eluting metal stents in renal artery of pig model.
AB  - BACKGROUND AND PURPOSE: Recent reports concerning coronary, carotid, and femoral
      vasculature have proposed the use of drug-eluting metal stents (MS) to improve
      clinical and angiographic outcomes. Based on these reports, we used paclitaxel
      eluting MS within an animal renal artery lumen and compared the results with
      those using a bare-metal stent. MATERIALS AND METHODS: The experimental model in
      this study was the female pig renal artery. Ten pigs with weights ranging from 25
      to 30 kg were used. Twenty stents were placed, two in each animal. The MS
      placement was randomly performed in either the right or left renal artery of each
      animal. In 10 arteries, a 3.5 x 18 mm R-stent (group A) was placed; in the
      remaining 10 arteries, a 3 x 32 mm paclitaxel-eluting coronary stent (T-stent,
      group B) was inserted. Patency was estimated with the use of digital subtraction
      angiography, CT angiography, and virtual endoscopy at 24 hours and 1 month
      poststent placement. RESULTS: The positioning of the MS was successful in all
      cases. The initial angiographic result was maintained 24 hours after the
      intervention. No stent migration was seen, except for one paclitaxel stent that
      was acutely occluded. The one-month patency rate, as demonstrated by angiography,
      CT angiography, and virtual endoscopy, was 70% (8 arteries) in group A and 90% (9
      arteries) in group B. The thickness of the endothelium and of the muscular coat
      was statistically significantly less in group B compared with group A (P = 0.0352
      and P = 0.0046, respectively). CONCLUSION: These preliminary experimental study
      results suggest that the paclitaxel-eluting MS is more efficient than the bare
      metal stent when used within the pig renal artery. Further experimental and
      clinical studies are necessary to validate our preliminary encouraging results.

PMID- 18044995
TI  - Case report: hand-assisted laparoscopic radical heminephrectomy for renal-cell
      carcinoma in a horseshoe kidney.
AB  - A 63-year-old woman with an incidentally detected 10-cm enhancing renal mass in
      the left moiety of a horseshoe kidney was treated with a transperitoneal hand
      assisted laparoscopic (HAL) radical heminephrectomy. The operative time was 273
      minutes, and estimated blood loss was 250 mL. To our knowledge, this is the
      initial case of HAL radical heminephrectomy for renal-cell carcinoma in a
      horseshoe kidney. Appropriate pre-operative imaging and surgical technique for
      the isthmusectomy are highlighted.

PMID- 18044996
TI  - Comparison of conventional and step-wise shockwave lithotripsy in management of
      urinary calculi.
AB  - PURPOSE: In this clinical study, our aim was to evaluate the results of
      conventional and step-wise shockwave lithotripsy (SWL) in the management of
      urinary calculi. PATIENTS AND METHODS: Fifty consecutive patients seen in our
      outpatient urology clinic were included and randomized in the clinical study. SWL
      was performed using a Dornier Compact Delta instrument. Treatment energy was set
      on 13 kV in the conventional group. In the step-wise SWL group, the patients were
      subjected to gradually increased (with every 500 shocks) output voltage as 11,
      12, and 13 kV, respectively. The SWL session was completed with 13 kV thereafter.
      The maximum number of shocks in both groups was limited to 3,000. RESULTS: Twenty
      five patients in the conventional group and 25 patients in the step-wise SWL were
      included. The mean ages in the step-wise SWL group and the conventional group
      were 39.9 and 41.4 years (P > 0.05), respectively. The mean stone size was 0.83
      +/- 0.51 cm in the step-wise SWL group and 0.70 +/- 0.41 cm in the conventional
      group (P > 0.05). There was no difference between the two groups as to the
      localization of stones in the ureter or kidney. Also, no statistical difference
      was observed in the number of lithotripsy treatments between the two groups. When
      we compared the results of two treatment procedures 8 weeks after the initial
      treatment, the success rate was significantly higher in the step-wise SWL group
      than in the conventional group (stone-free rate 96% (24/25) v 72% (18/25), P <
      0.05)). CONCLUSIONS: Step-wise SWL yielded better outcomes than conventional SWL
      without increased morbidity. Stepwise SWL can be considered as a management
      option for urinary calculi.

PMID- 18044997
TI  - Broadcast of live endoscopic surgery from Korea to Japan using the digital video
      transport system.
AB  - PURPOSE: To assess the quality of sound and uncompressed images during an
      international broadcast of live surgery using the newly developed digital video
      transport system (DVTS). METHODS: Three networks connected hospitals in Seoul,
      Korea, and Fukuoka, Japan. A teleconference system with bidirectional
      transmission over the network was set up. DVTS was used to send and receive
      visual and audio signals during a live broadcast of a laparoscopic partial
      nephrectomy to viewers at the 94th annual meeting of the Japanese Urological
      Association. A questionnaire was used to assess the quality of images and sound.
      RESULTS: Of 713 questionnaires distributed, 418 were collected. The quality of
      image and voice was ranked very good or good by 95% and 92% of the audience,
      respectively. The quality of live surgery was considered high by 94% of the
      audience. CONCLUSION: Digital video images can be transformed directly to an
      Internet protocol without compression of the motion images using DVTS. Live
      surgery via teleconference using DVTS can help surgeons learn the skills of
      endoscopic surgery.

PMID- 18044998
TI  - Sural nerve grafting in robotic laparoscopic radical prostatectomy: interim
      report.
AB  - BACKGROUND AND PURPOSE: Sural nerve grafting for patients undergoing
      prostatectomy has been previously reported using open and minimally invasive
      methods. We report our experience with sural nerve grafting during robot-assisted
      laparoscopic radical prostatectomy (RLRP). MATERIALS AND METHODS: Patients with
      preoperative potency and a minimum of 6 months follow-up were included in this
      prospective review. A total of 333 patients were identified between February 2003
      and January 2006 who met these criteria including 22 of the 25 patients who
      underwent sural nerve grafting. Patients were divided into 5 groups to compare
      unilateral and bilateral sural nerve cohorts with non-nerve-sparing and
      unilateral and bilateral nerve-sparing groups. Patients were followed
      prospectively using health-related quality-of-life questionnaires. RESULTS:
      Twenty-two patients underwent sural nerve grafting that included three bilateral
      grafts. Mean follow-up was 14 months. There was no statistical difference in
      patients' ages, body mass index, preoperative prostate-specific antigen level,
      blood loss, complications, and positive margin rate. Operative time was
      statistically longer for both sural graft cohorts when compared with unilateral
      (without graft) and bilateral nerve sparing cohorts. No significant differences
      in subjective or objective sexual function, sexual bother, or urinary function
      were seen with 6 and 12 months follow-up, possibly related to smaller sural
      cohorts. Graft-related complications include leg pain in one patient. CONCLUSION:
      Sural nerve grafting during RLRP is technically feasible and safe and offers
      improved dexterity and visualization deep within the pelvis. However, a larger
      randomized cohort of patients will be required to validate any improved benefits
      afforded by the robot system.

PMID- 18044999
TI  - The high-conductance state of cortical networks.
AB  - We studied the dynamics of large networks of spiking neurons with conductance
      based (nonlinear) synapses and compared them to networks with current-based
      (linear) synapses. For systems with sparse and inhibition-dominated recurrent
      connectivity, weak external inputs induced asynchronous irregular firing at low
      rates. Membrane potentials fluctuated a few millivolts below threshold, and
      membrane conductances were increased by a factor 2 to 5 with respect to the
      resting state. This combination of parameters characterizes the ongoing spiking
      activity typically recorded in the cortex in vivo. Many aspects of the
      asynchronous irregular state in conductance-based networks could be sufficiently
      well characterized with a simple numerical mean field approach. In particular, it
      correctly predicted an intriguing property of conductance-based networks that
      does not appear to be shared by current-based models: they exhibit states of low
      rate asynchronous irregular activity that persist for some period of time even in
      the absence of external inputs and without cortical pacemakers. Simulations of
      larger networks (up to 350,000 neurons) demonstrated that the survival time of
      self-sustained activity increases exponentially with network size.

PMID- 18045000
TI  - Irregular firing of isolated cortical interneurons in vitro driven by intrinsic
      stochastic mechanisms.
AB  - Pharmacologically isolated GABAergic irregular spiking and stuttering
      interneurons in the mouse visual cortex display highly irregular spike times,
      with high coefficients of variation approximately 0.9-3, in response to a
      depolarizing, constant current input. This is in marked contrast to cortical
      pyramidal cells, which spike quite regularly in response to the same current
      injection. We applied time-series analysis methods to show that the irregular
      behavior of the interneurons was not a consequence of low-dimensional,
      deterministic processes. These methods were also applied to the Hindmarsh and
      Rose neuronal model to confirm that the methods are adequate for the types of
      data under investigation. This result has important consequences for the origin
      of fluctuations observed in the cortex in vivo.

PMID- 18045001
TI  - A very simple spiking neuron model that allows for modeling of large, complex
      systems.
AB  - This letter introduces a biologically inspired very simple spiking neuron model.
      The model retains only crucial aspects of biological neurons: a network of time
      delayed weighted connections to other neurons, a threshold-based generation of
      action potentials, action potential frequency proportional to stimulus intensity,
      and interneuron communication that occurs with time-varying potentials that last
      longer than the associated action potentials. The key difference between this
      model and existing spiking neuron models is its great simplicity: it is basically
      a collection of linear and discontinuous functions with no differential equations
      to solve. The model's ability to operate in a complex network was tested by using
      it as a basis of a network implementing a hypothetical echolocation system. The
      system consists of an emitter and two receivers. The outputs of the receivers are
      connected to a network of spiking neurons (using the proposed model) to form a
      detection grid that acts as a map of object locations in space. The network uses
      differences in the arrival times of the signals to determine the azimuthal angle
      of the source and time of flight to calculate the distance. The activation
      patterns observed indicate that for a network of spiking neurons, which uses only
      time delays to determine source locations, the spatial discrimination varies with
      the number and relative spacing of objects. These results are similar to those
      observed in animals that use echolocation.

PMID- 18045002
TI  - Bayesian spiking neurons I: inference.
AB  - We show that the dynamics of spiking neurons can be interpreted as a form of
      Bayesian inference in time. Neurons that optimally integrate evidence about
      events in the external world exhibit properties similar to leaky integrate-and
      fire neurons with spike-dependent adaptation and maximally respond to
      fluctuations of their input. Spikes signal the occurrence of new information-what
      cannot be predicted from the past activity. As a result, firing statistics are
      close to Poisson, albeit providing a deterministic representation of
      probabilities.

PMID- 18045003
TI  - Bayesian spiking neurons II: learning.
AB  - In the companion letter in this issue ("Bayesian Spiking Neurons I: Inference"),
      we showed that the dynamics of spiking neurons can be interpreted as a form of
      Bayesian integration, accumulating evidence over time about events in the
      external world or the body. We proceed to develop a theory of Bayesian learning
      in spiking neural networks, where the neurons learn to recognize temporal
      dynamics of their synaptic inputs. Meanwhile, successive layers of neurons learn
      hierarchical causal models for the sensory input. The corresponding learning rule
      is local, spike-time dependent, and highly nonlinear. This approach provides a
      principled description of spiking and plasticity rules maximizing information
      transfer, while limiting the number of costly spikes, between successive layers
      of neurons.

PMID- 18045004
TI  - Population coding with motion energy filters: the impact of correlations.
AB  - The codes obtained from the responses of large populations of neurons are known
      as population codes. Several studies have shown that the amount of information
      conveyed by such codes, and the format of this information, is highly dependent
      on the pattern of correlations. However, very little is known about the impact of
      response correlations (as found in actual cortical circuits) on neural coding. To
      address this problem, we investigated the properties of population codes obtained
      from motion energy filters, which provide one of the best models for motion
      selectivity in early visual areas. It is therefore likely that the correlations
      that arise among energy filters also arise among motion-selective neurons. We
      adopted an ideal observer approach to analyze filter responses to three sets of
      images: noisy sine gratings, random dots kinematograms, and images of natural
      scenes. We report that in our model, the structure of the population code varies
      with the type of image. We also show that for all sets of images, correlations
      convey a large fraction of the information: 40% to 90% of the total information.
      Moreover, ignoring those correlations when decoding leads to considerable
      information loss-from 50% to 93%, depending on the image type. Finally we show
      that it is important to consider a large population of motion energy filters in
      order to see the impact of correlations. Study of pairs of neurons, as is often
      done experimentally, can underestimate the effect of correlations.

PMID- 18045005
TI  - Feedback decoding of spatially structured population activity in cortical maps.
AB  - A mechanism is proposed by which feedback pathways model spatial patterns of
      feedforward activity in cortical maps. The mechanism can be viewed equivalently
      as readout of a content-addressable memory or as decoding of a population code.
      The model is based on the evidence that cortical receptive fields can often be
      described as a separable product of functions along several dimensions, each
      represented in a spatially ordered map. Given this, it is shown that for an N
      dimensional map, accurate modeling and decoding of x(N) feedforward activity
      patterns can be done with Nx fibers, N of which must be active at any one time.
      The proposed mechanism explains several known properties of the cortex and
      pyramidal neurons: (1) the integration of signals by dendrites with a narrow
      tangential distribution, that is, apical dendrites; (2) the presence of fast
      conducting feedback projections with broad tangential distributions; (3) the
      multiplicative effects of attention on receptive field profiles; and (4) the
      existence of multiplicative interactions between subthreshold feedforward inputs
      to basal dendrites and inputs to apical dendrites.

PMID- 18045006
TI  - Chaotic frequency scaling in a coupled oscillator model for free rhythmic
      actions.
AB  - The question of how best to model rhythmic movements at self-selected amplitude
      frequency combinations, and their variability, is a long-standing issue. This
      study presents a systematic analysis of a coupled oscillator system that has
      successfully accounted for the experimental result that humans' preferred
      oscillation frequencies closely correspond to the linear resonance frequencies of
      the biomechanical limb systems, a phenomenon known as resonance tuning or
      frequency scaling. The dynamics of the coupled oscillator model is explored by
      numerical integration in different areas of its parameter space, where a period
      doubling route to chaotic dynamics is discovered. It is shown that even in the
      regions of the parameter space with chaotic solutions, the model still
      effectively scales to the biomechanical oscillator's natural frequency. Hence,
      there is a solution providing for frequency scaling in the presence of chaotic
      variability. The implications of these results for interpreting variability as
      fundamentally stochastic or chaotic are discussed.

PMID- 18045007
TI  - The actor-critic learning is behind the matching law: matching versus optimal
      behaviors.
AB  - The ability to make a correct choice of behavior from various options is crucial
      for animals' survival. The neural basis for the choice of behavior has been
      attracting growing attention in research on biological and artificial neural
      systems. Alternative choice tasks with variable ratio (VR) and variable interval
      (VI) schedules of reinforcement have often been employed in studying decision
      making by animals and humans. In the VR schedule task, alternative choices are
      reinforced with different probabilities, and subjects learn to select the
      behavioral response rewarded more frequently. In the VI schedule task,
      alternative choices are reinforced at different average intervals independent of
      the choice frequencies, and the choice behavior follows the so-called matching
      law. The two policies appear robustly in subjects' choice of behavior, but the
      underlying neural mechanisms remain unknown. Here, we show that these seemingly
      different policies can appear from a common computational algorithm known as
      actor-critic learning. We present experimentally testable variations of the VI
      schedule in which the matching behavior gives only a suboptimal solution to
      decision making and show that the actor-critic system exhibits the matching
      behavior in the steady state of the learning even when the matching behavior is
      suboptimal. However, it is found that the matching behavior can earn
      approximately the same reward as the optimal one in many practical situations.

PMID- 18045008
TI  - Minimization of error functionals over perceptron networks.
AB  - Supervised learning of perceptron networks is investigated as an optimization
      problem. It is shown that both the theoretical and the empirical error
      functionals achieve minima over sets of functions computable by networks with a
      given number n of perceptrons. Upper bounds on rates of convergence of these
      minima with n increasing are derived. The bounds depend on a certain regularity
      of training data expressed in terms of variational norms of functions
      interpolating the data (in the case of the empirical error) and the regression
      function (in the case of the expected error). Dependence of this type of
      regularity on dimensionality and on magnitudes of partial derivatives is
      investigated. Conditions on the data, which guarantee that a good approximation
      of global minima of error functionals can be achieved using networks with a
      limited complexity, are derived. The conditions are in terms of oscillatory
      behavior of the data measured by the product of a function of the number of
      variables d, which is decreasing exponentially fast, and the maximum of the
      magnitudes of the squares of the L(1)-norms of the iterated partial derivatives
      of the order d of the regression function or some function, which interpolates
      the sample of the data. The results are illustrated by examples of data with
      small and high regularity constructed using Boolean functions and the gaussian
      function.

PMID- 18045009
TI  - An SMO algorithm for the potential support vector machine.
AB  - We describe a fast sequential minimal optimization (SMO) procedure for solving
      the dual optimization problem of the recently proposed potential support vector
      machine (P-SVM). The new SMO consists of a sequence of iteration steps in which
      the Lagrangian is optimized with respect to either one (single SMO) or two (dual
      SMO) of the Lagrange multipliers while keeping the other variables fixed. An
      efficient selection procedure for Lagrange multipliers is given, and two
      heuristics for improving the SMO procedure are described: block optimization and
      annealing of the regularization parameter epsilon. A comparison of the variants
      shows that the dual SMO, including block optimization and annealing, performs
      efficiently in terms of computation time. In contrast to standard support vector
      machines (SVMs), the P-SVM is applicable to arbitrary dyadic data sets, but
      benchmarks are provided against libSVM's epsilon-SVR and C-SVC implementations
      for problems that are also solvable by standard SVM methods. For those problems,
      computation time of the P-SVM is comparable to or somewhat higher than the
      standard SVM. The number of support vectors found by the P-SVM is usually much
      smaller for the same generalization performance.

PMID- 18045010
TI  - On the classification capability of sign-constrained perceptrons.
AB  - The perceptron (also referred to as McCulloch-Pitts neuron, or linear threshold
      gate) is commonly used as a simplified model for the discrimination and learning
      capability of a biological neuron. Criteria that tell us when a perceptron can
      implement (or learn to implement) all possible dichotomies over a given set of
      input patterns are well known, but only for the idealized case, where one assumes
      that the sign of a synaptic weight can be switched during learning. We present in
      this letter an analysis of the classification capability of the biologically more
      realistic model of a sign-constrained perceptron, where the signs of synaptic
      weights remain fixed during learning (which is the case for most types of
      biological synapses). In particular, the VC-dimension of sign-constrained
      perceptrons is determined, and a necessary and sufficient criterion is provided
      that tells us when all 2(m) dichotomies over a given set of m patterns can be
      learned by a sign-constrained perceptron. We also show that uniformity of L(1)
      norms of input patterns is a sufficient condition for full representation power
      in the case where all weights are required to be nonnegative. Finally, we exhibit
      cases where the sign constraint of a perceptron drastically reduces its
      classification capability. Our theoretical analysis is complemented by computer
      simulations, which demonstrate in particular that sparse input patterns improve
      the classification capability of sign-constrained perceptrons.

PMID- 18045011
TI  - STDP provides the substrate for igniting synfire chains by spatiotemporal input
      patterns.
AB  - Spike-timing-dependent synaptic plasticity (STDP), which depends on the temporal
      difference between pre- and postsynaptic action potentials, is observed in the
      cortices and hippocampus. Although several theoretical and experimental studies
      have revealed its fundamental aspects, its functional role remains unclear. To
      examine how an input spatiotemporal spike pattern is altered by STDP, we observed
      the output spike patterns of a spiking neural network model with an asymmetrical
      STDP rule when the input spatiotemporal pattern is repeatedly applied. The
      spiking neural network comprises excitatory and inhibitory neurons that exhibit
      local interactions. Numerical experiments show that the spiking neural network
      generates a single global synchrony whose relative timing depends on the input
      spatiotemporal pattern and the neural network structure. This result implies that
      the spiking neural network learns the transformation from spatiotemporal to
      temporal information. In the literature, the origin of the synfire chain has not
      been sufficiently focused on. Our results indicate that spiking neural networks
      with STDP can ignite synfire chains in the cortices.

PMID- 18045012
TI  - Second-order SMO improves SVM online and active learning.
AB  - Iterative learning algorithms that approximate the solution of support vector
      machines (SVMs) have two potential advantages. First, they allow online and
      active learning. Second, for large data sets, computing the exact SVM solution
      may be too time-consuming, and an efficient approximation can be preferable. The
      powerful LASVM iteratively approaches the exact SVM solution using sequential
      minimal optimization (SMO). It allows efficient online and active learning. Here,
      this algorithm is considerably improved in speed and accuracy by replacing the
      working set selection in the SMO steps. A second-order working set selection
      strategy, which greedily aims at maximizing the progress in each single step, is
      incorporated.

PMID- 18045013
TI  - Bayesian model comparison in nonlinear BOLD fMRI hemodynamics.
AB  - Nonlinear hemodynamic models express the BOLD (blood oxygenation level dependent)
      signal as a nonlinear, parametric functional of the temporal sequence of local
      neural activity. Several models have been proposed for both the neural activity
      and the hemodynamics. We compare two such combined models: the original balloon
      model with a square-pulse neural model (Friston, Mechelli, Turner, & Price, 2000)
      and an extended balloon model with a more sophisticated neural model (Buxton,
      Uludag, Dubowitz, & Liu, 2004). We learn the parameters of both models using a
      Bayesian approach, where the distribution of the parameters conditioned on the
      data is estimated using Markov chain Monte Carlo techniques. Using a split-half
      resampling procedure (Strother, Anderson, & Hansen, 2002), we compare the
      generalization abilities of the models as well as their reproducibility, for both
      synthetic and real data, recorded from two different visual stimulation
      paradigms. The results show that the simple model is the better one for these
      data.

PMID- 18045014
TI  - Implications of noise and neural heterogeneity for vestibulo-ocular reflex
      fidelity.
AB  - The vestibulo-ocular reflex (VOR) is characterized by a short-latency, high
      fidelity eye movement response to head rotations at frequencies up to 20 Hz.
      Electrophysiological studies of medial vestibular nucleus (MVN) neurons, however,
      show that their response to sinusoidal currents above 10 to 12 Hz is highly
      nonlinear and distorted by aliasing for all but very small current amplitudes.
      How can this system function in vivo when single cell response cannot explain its
      operation? Here we show that the necessary wide VOR frequency response may be
      achieved not by firing rate encoding of head velocity in single neurons, but in
      the integrated population response of asynchronously firing, intrinsically active
      neurons. Diffusive synaptic noise and the pacemaker-driven, intrinsic firing of
      MVN cells synergistically maintain asynchronous, spontaneous spiking in a
      population of model MVN neurons over a wide range of input signal amplitudes and
      frequencies. Response fidelity is further improved by a reciprocal inhibitory
      link between two MVN populations, mimicking the vestibular commissural system in
      vivo, but only if asynchrony is maintained by noise and pacemaker inputs. These
      results provide a previously missing explanation for the full range of VOR
      function and a novel account of the role of the intrinsic pacemaker conductances
      in MVN cells. The values of diffusive noise and pacemaker currents that give
      optimal response fidelity yield firing statistics similar to those in vivo,
      suggesting that the in vivo network is tuned to optimal performance. While
      theoretical studies have argued that noise and population heterogeneity can
      improve coding, to our knowledge this is the first evidence indicating that these
      parameters are indeed tuned to optimize coding fidelity in a neural control
      system in vivo.

PMID- 18045015
TI  - Robust L1 principal component analysis and its Bayesian variational inference.
AB  - We introduce a robust probabilistic L1-PCA model in which the conventional
      gaussian distribution for the noise in the observed data was replaced by the
      Laplacian distribution (or L1 distribution). Due to the heavy tail
      characteristics of the L1 distribution, the proposed model is supposed to be more
      robust against data outliers. In this letter, we demonstrate how a variational
      approximation scheme enables effective inference of key parameters in the
      probabilistic L1-PCA model. As the L1 density can be expanded as a superposition
      of infinite number of gaussian densities, we express the L1-PCA model as a
      marginalized model over the superpositions. By doing so, a tractable Bayesian
      inference can be achieved based on the variational expectation-maximization-type
      algorithm.

PMID- 18045016
TI  - A principle for learning egocentric-allocentric transformation.
AB  - Numerous single-unit recording studies have found mammalian hippocampal neurons
      that fire selectively for the animal's location in space, independent of its
      orientation. The population of such neurons, commonly known as place cells, is
      thought to maintain an allocentric, or orientation-independent, internal
      representation of the animal's location in space, as well as mediating long-term
      storage of spatial memories. The fact that spatial information from the
      environment must reach the brain via sensory receptors in an inherently
      egocentric, or viewpoint-dependent, fashion leads to the question of how the
      brain learns to transform egocentric sensory representations into allocentric
      ones for long-term memory storage. Additionally, if these long-term memory
      representations of space are to be useful in guiding motor behavior, then the
      reverse transformation, from allocentric to egocentric coordinates, must also be
      learned. We propose that orientation-invariant representations can be learned by
      neural circuits that follow two learning principles: minimization of
      reconstruction error and maximization of representational temporal inertia. Two
      different neural network models are presented that adhere to these learning
      principles, the first by direct optimization through gradient descent and the
      second using a more biologically realistic circuit based on the restricted
      Boltzmann machine (Hinton, 2002; Smolensky, 1986). Both models lead to
      orientation-invariant representations, with the latter demonstrating place-cell
      like responses when trained on a linear track environment.

PMID- 18045017
TI  - Minimum acceleration criterion with constraints implies bang-bang control as an
      underlying principle for optimal trajectories of arm reaching movements.
AB  - Rapid arm-reaching movements serve as an excellent test bed for any theory about
      trajectory formation. How are these movements planned? A minimum acceleration
      criterion has been examined in the past, and the solution obtained, based on the
      Euler-Poisson equation, failed to predict that the hand would begin and end the
      movement at rest (i.e., with zero acceleration). Therefore, this criterion was
      rejected in favor of the minimum jerk, which was proved to be successful in
      describing many features of human movements. This letter follows an alternative
      approach and solves the minimum acceleration problem with constraints using
      Pontryagin's minimum principle. We use the minimum principle to obtain minimum
      acceleration trajectories and use the jerk as a control signal. In order to find
      a solution that does not include nonphysiological impulse functions, constraints
      on the maximum and minimum jerk values are assumed. The analytical solution
      provides a three-phase piecewise constant jerk signal (bang-bang control) where
      the magnitude of the jerk and the two switching times depend on the magnitude of
      the maximum and minimum available jerk values. This result fits the observed
      trajectories of reaching movements and takes into account both the extrinsic
      coordinates and the muscle limitations in a single framework. The minimum
      acceleration with constraints principle is discussed as a unifying approach for
      many observations about the neural control of movements.

PMID- 18045018
TI  - A sensorimotor approach to sound localization.
AB  - Sound localization is known to be a complex phenomenon, combining multisensory
      information processing, experience-dependent plasticity, and movement. Here we
      present a sensorimotor model that addresses the question of how an organism could
      learn to localize sound sources without any a priori neural representation of its
      head-related transfer function or prior experience with auditory spatial
      information. We demonstrate quantitatively that the experience of the sensory
      consequences of its voluntary motor actions allows an organism to learn the
      spatial location of any sound source. Using examples from humans and echolocating
      bats, our model shows that a naive organism can learn the auditory space based
      solely on acoustic inputs and their relation to motor states.

PMID- 18045019
TI  - How optimal stimuli for sensory neurons are constrained by network architecture.
AB  - Identifying the optimal stimuli for a sensory neuron is often a difficult process
      involving trial and error. By analyzing the relationship between stimuli and
      responses in feedforward and stable recurrent neural network models, we find that
      the stimulus yielding the maximum firing rate response always lies on the
      topological boundary of the collection of all allowable stimuli, provided that
      individual neurons have increasing input-output relations or gain functions and
      that the synaptic connections are convergent between layers with nondegenerate
      weight matrices. This result suggests that in neurophysiological experiments
      under these conditions, only stimuli on the boundary need to be tested in order
      to maximize the response, thereby potentially reducing the number of trials
      needed for finding the most effective stimuli. Even when the gain functions allow
      firing rate cutoff or saturation, a peak still cannot exist in the stimulus
      response relation in the sense that moving away from the optimum stimulus always
      reduces the response. We further demonstrate that the condition for nondegenerate
      synaptic connections also implies that proper stimuli can independently perturb
      the activities of all neurons in the same layer. One example of this type of
      manipulation is changing the activity of a single neuron in a given processing
      layer while keeping that of all others constant. Such stimulus perturbations
      might help experimentally isolate the interactions of selected neurons within a
      network.

PMID- 18045020
TI  - Dynamics of learning near singularities in layered networks.
AB  - We explicitly analyze the trajectories of learning near singularities in
      hierarchical networks, such as multilayer perceptrons and radial basis function
      networks, which include permutation symmetry of hidden nodes, and show their
      general properties. Such symmetry induces singularities in their parameter space,
      where the Fisher information matrix degenerates and odd learning behaviors,
      especially the existence of plateaus in gradient descent learning, arise due to
      the geometric structure of singularity. We plot dynamic vector fields to
      demonstrate the universal trajectories of learning near singularities. The
      singularity induces two types of plateaus, the on-singularity plateau and the
      near-singularity plateau, depending on the stability of the singularity and the
      initial parameters of learning. The results presented in this letter are
      universally applicable to a wide class of hierarchical models. Detailed stability
      analysis of the dynamics of learning in radial basis function networks and
      multilayer perceptrons will be presented in separate work.

PMID- 18045022
TI  - A neural network model of the Eriksen task: reduction, analysis, and data
      fitting.
AB  - We analyze a neural network model of the Eriksen task: a two-alternative forced
      choice task in which subjects must correctly identify a central stimulus and
      disregard flankers that may or may not be compatible with it. We linearize and
      decouple the model, deriving a reduced drift-diffusion process with variable
      drift rate that describes the accumulation of net evidence in favor of either
      alternative, and we use this to analytically describe how accuracy and response
      time data depend on model parameters. Such analyses both assist parameter tuning
      in network models and suggest explanations of changing drift rates in terms of
      attention. We compare our results with numerical simulations of the full
      nonlinear model and with empirical data and show good fits to both with fewer
      parameters.

PMID- 18045023
TI  - Neural network models for conditional distribution under bayesian analysis.
AB  - We use neural networks (NN) as a tool for a nonlinear autoregression to predict
      the second moment of the conditional density of return series. The NN models are
      compared to the popular econometric GARCH(1,1) model. We estimate the models in a
      Bayesian framework using Markov chain Monte Carlo posterior simulations. The
      interlinked aspects of the proposed Bayesian methodology are identification of NN
      hidden units and treatment of NN complexity based on model evidence. The
      empirical study includes the application of the designed strategy to market data,
      where we found a strong support for a nonlinear multilayer perceptron model with
      two hidden units.

PMID- 18045024
TI  - Generation of optimal artificial neural networks using a pattern search
      algorithm: application to approximation of chemical systems.
AB  - A pattern search optimization method is applied to the generation of optimal
      artificial neural networks (ANNs). Optimization is performed using a mixed
      variable extension to the generalized pattern search method. This method offers
      the advantage that categorical variables, such as neural transfer functions and
      nodal connectivities, can be used as parameters in optimization. When used
      together with a surrogate, the resulting algorithm is highly efficient for
      expensive objective functions. Results demonstrate the effectiveness of this
      method in optimizing an ANN for the number of neurons, the type of transfer
      function, and the connectivity among neurons. The optimization method is applied
      to a chemistry approximation of practical relevance. In this application,
      temperature and a chemical source term are approximated as functions of two
      independent parameters using optimal ANNs. Comparison of the performance of
      optimal ANNs with conventional tabulation methods demonstrates equivalent
      accuracy by considerable savings in memory storage. The architecture of the
      optimal ANN for the approximation of the chemical source term consists of a fully
      connected feedforward network having four nonlinear hidden layers and 117
      synaptic weights. An equivalent representation of the chemical source term using
      tabulation techniques would require a 500 x 500 grid point discretization of the
      parameter space.

PMID- 18045025
TI  - Valuations for spike train prediction.
AB  - The ultimate product of an electrophysiology experiment is often a decision on
      which biological hypothesis or model best explains the observed data. We outline
      a paradigm designed for comparison of different models, which we refer to as
      spike train prediction. A key ingredient of this paradigm is a prediction quality
      valuation that estimates how close a predicted conditional intensity function is
      to an actual observed spike train. Although a valuation based on log likelihood
      (L) is most natural, it has various complications in this context. We propose
      that a quadratic valuation (Q) can be used as an alternative to L. Q shares some
      important theoretical properties with L, including consistency, and the two
      valuations perform similarly on simulated and experimental data. Moreover, Q is
      more robust than L, and optimization with Q can dramatically improve
      computational efficiency. We illustrate the utility of Q for comparing models of
      peer prediction, where it can be computed directly from cross-correlograms.
      Although Q does not have a straightforward probabilistic interpretation, Q is
      essentially given by Euclidean distance.

PMID- 18045026
TI  - Migration of dendritic cell subsets and their precursors.
AB  - The ability of dendritic cells (DCs) to initiate and orchestrate immune responses
      is a consequence of their localization within tissues and their specialized
      capacity for mobilization. The migration of a given DC subset is typified by a
      restricted capacity for recirculation, contrasting markedly with T cells. Routes
      of DC migration into lymph nodes differ notably for distinct DC subsets. Here, we
      compare the distinct migratory patterns of plasmacytoid DCs (pDCs), CD8alpha(+)
      DCs, Langerhans cells, and conventional myeloid DCs and discuss how the highly
      regulated patterns of DC migration in vivo may affect their roles in immunity.
      Finally, to gain a more molecular appreciation of the specialized migratory
      properties of DCs, we review the signaling cascades that govern the process of DC
      migration.

PMID- 18045027
TI  - [From renal osteodistrophy to bone and mineral metabolism lesions associated to
      renal chronic disease].

PMID- 18045028
TI  - [Are IL2 receptor antagonist useful in high risk acute tubular necrosis kidney
      recipients?].
AB  - The questions are if old recipients from old donor have more incidence of delayed
      graft function and if antagonists of Il-2 receptors use decreased the incidence
      of NTA post-transplant. To answer the first question we have come to information
      from registry and uni or multicenter studies. We have used the Irish normograme
      that included 16 clinical questions from donors, recipients and kidney
      transplant. We concluded that age of donors increases likelihood of delayed graft
      function. The second question is answered in the literature with information of a
      meta-analysis with 38 clinical studies. Of them 9 (1.380 patients) studied
      delayed graft function and are against placebo. The odds ratio for delayed graft
      function was 0.87(IC 95% 0,72 a 1,06). Therefore, at the moment, we can conclude
      that the utilization of antagonists of Il-2 receptors does not have protective
      effect to NTA.

PMID- 18045029
TI  - [Notes for the critical lecture of a prognostic article].

PMID- 18045030
TI  - [Developing a Clinical Performance Measures System for hemodialysis, Quality
      Group, Spanish Society of Nephrology].

PMID- 18045031
TI  - [Antiphospholipid syndrome and lupus nephritis treated with rituximab].

PMID- 18045032
TI  - [Cyclosporin A causes oxidative stress and mitochondrial dysfunction in renal
      tubular cells].
AB  - Reactive oxygen species (ROS) have been implicated in cyclosporin A (CsA)
      nephrotoxicity. As mitochondria are one of the main sources of ROS in cells, we
      evaluated the role of CsA in mitochondrial structure and function in LLC-PK1
      cells. We incubated cells with CsA 1 microM for 24 hours and studies were
      performed with flow citometry and confocal microscopy. We studied mitochondrial
      NAD(P)H content, superoxide anion (O2.-) production (MitoSOX Red), oxidation of
      cardiolipin of inner mitochondrial membrane (NAO) and mitochondrial membrane
      potential (DIOC2(3)). Also we analyzed the intracellular ROS synthesis (H2DCF-DA)
      and reduced glutation (GSH) of cells. Our results showed that CsA decreased
      NAD(P)H and membrane potential, and increased O2.- in mitochondria. CsA also
      provoked oxidation of cardiolipin. Furthermore, CsA increased intracellular ROS
      production and decreased GSH content. These results suggest that CsA has crucial
      effects in mitochondria. CsA modified mitochondrial physiology through the
      decrease of antioxidant mitochondrial compounds as NAD(P)H and the dissipation of
      mitochondrial membrane potential and increase of oxidants as O2.-. Also, CsA
      alters lipidic structure of inner mitochondrial membrane through the oxidation of
      cardiolipin. These effects trigger a chain of events that favour intracellular
      synthesis of ROS and depletion of GSH that can compromise cellular viability.
      Nephrotoxic cellular effects of CsA can be explained, at least in part, through
      its influence on mitochondrial functionalism.

PMID- 18045033
TI  - [Choosing not to dialysis in chronic renal failure in stage V (Renal Failure).
      Evolution of the characteristics of patients between 1992-1995 and 2000-2003].
AB  - BACKGROUND: The incidence of chronic renal failure increase with the age. The
      selection of patient to dialysis has been increasing in spite of the high
      comorbidity. Moreover, in our clinical practice the aged patient is not
      contraindicated to dialysis. However, in the nephrology clinical practice not all
      the patients start the treatment with dialysis. OBJECTIVE The aim of our study
      has been to compare the characteristics of the patients who had not been dialyzed
      between the periods 1992-1995 and 2000-2003 to analyze the trend of the
      nephrology clinical practice. MATERIAL AND METHODS: Comparative study of the
      characteristics and the evolution of patients with chronic renal failure in stage
      V, (renal failure) not incorporated to dialysis in one hospital during four years
      between the periods the 1992-1995 ( period A) and 2000-2003 (period B). RESULTS:
      Start dialysis (period A versus period B): 116 patients, age 59.9+15.5 years vs.
      229 patients, age 64.0+15.8 years (p<0.05). Non-dialysis (period A versus period
      B): 38 patients, age 77.5+9.3 years vs. 37 patients, age 81.7+6.2 years (p<0.01).
      Renal function: serum creatinina 7.4+2.4 mg/dl vs. 5.3+1.2 mg/dl (p<0.001), MDRD
      estimate glomerular filtration 6.9+2.4 mg/dl ml/min/1.73 m2 vs. 10.0+2.3
      ml/min/1.73 m2 (p<0.001). Primary renal disease: unknown etiology 31.5 % vs. 24.3
      %, nephroangiosclerosis 23.6 % vs. 32.4 %, diabetes 28.9 % vs. 21.6 %. Functional
      status: dependent patients 34.2 % vs 83.8 % (p<0.001). The principal reason for
      non-dialysis were: personal decision: 26.3 % vs. 35.1 %, dementia 15.8 % vs. 29.7
      %, brief life expectancy because of serious co-existing diseases 13.1 % vs. 21.7
      % and serious chronic illness with inability for themselves care 44.7 % vs. 13.1
      %. Comorbid conditions: 2.3+1.0 vs. 3.0+1.5 (p<0.05). Survival: 55+168 days vs.
      168+236 days (p<0.001). CONCLUSION: Most of the patients that don't begin
      dialysis are elderly together with a poor functional capacity and with more
      autonomy in their decisions. The identification of patients with renal failure
      (stage V) was detected early in the last period than in the following one. The
      conservative management of non-dialyzed uremic patients is a significative
      nephrology clinical practice due to more survival of those persons.

PMID- 18045034
TI  - [Advance directives in chronic dialysis patients].
AB  - BACKGROUND AND OBJECTIVE: Knowledge of the life-sustaining treatment preferences
      of the dialysis patients would be extremely helpful to substitute decision-makers
      and nephrologists in deciding whether to continue or stop a treatment. The
      population of the Mediterranean countries show this opinion with less frequency.
      The objective of this study is: 1) the knowledge of the patient's view for the
      advance directives; it may increase the likelihood to get the correct decisions
      of the staff when complications break the normal course of chronic dialysis, and
      2) the statement of the advance directives. MATERIAL AND METHOD: We distributed
      135 questionnaires to patients with chronic renal failure in dialysis treatment
      of the Sabadell's Hospital to explore demographic information about responders
      and not-responders and explore the rate of questionnaires was completed about the
      cardiopulmonary resuscitation, respirator, tube feeding and dialysis in case of
      coma, persistent vegetative state, severe dementia and terminal illness. We
      explore about the representative of patients and in case of not-responders about
      the cause to not answer. RESULTS: Sixty-four of 135 patients (47,8%) did not want
      cardiopulmonary resuscitation, respirator, tube feeding or dialysis in case of
      coma, persistent vegetative state, severe dementia or terminal illness. Compared
      with patients who wanted the treatments, those who did not were older (71,2
      versus 62,2 years; p = 0.002). There was no difference in the other demographic
      questions, including sex (p=0.674), cause of kidney failure (p=0.815), comorbid
      conditions (p=0.824), and social status (language of questionnaire -0.155- and
      standard of education -0.288-). Advance care planning does not occur solely
      within the context of the physician-patient relationship; the respondents
      reported the representative in the family, essentially. The patients not
      responders doesn t want to think in those situations and also they show doubt
      about the interpretation of their answers. CONCLUSIONS: near 50% patients in
      chronic dialysis want to stop certain treatments in case of resuscitation
      cardiopulmonary, coma, persistent vegetative state, severe dementia or terminal
      illness. The older patients want the limitation of treatments more frequently.

PMID- 18045035
TI  - [Kinetic of calcium, phosphate, magnesium and PTH variations during
      hemodiafiltration].
AB  - Hemodiafiltration (HDF) is a technique resulting from coupling of diffusive and
      convective transport and thereby increase the elimination of small and middle
      molecules. However, may induce a convective loss from others substances such as
      calcium and magnesium. The aim of this study was to evaluate the effects of
      Ultrafiltration on the kinetics of calcium, phosphate, magnesium and parathyroid
      hormone. A total of thirteen patients (7 males and 6 females) on hemodialysis,
      were studied. Each patient was randomly dialyzed with the same dialysate calcium
      concentration and three different ultrafiltration rate. Schedule A: High flux
      hemodialysis, schedule B: HDF with 10% of weight body and schedule C: HDF with
      20% of weight body. The others parameters were kept identical. Total
      Ultrafiltration was 2,6+/-0,9 L (9,78+/-3,78 ml/min) in A, 9,3+/-1,7 L (34,54+/
      6,22 ml/min) in B and 16,3+/-3,3 L (60,94+/-12,63 ml/min) in C. Replacement fluid
      during dialysis was 6,85+/-1,42 and 13,65+/-2,9 L. in C and C respectively.
      Postdialysis total,ionized calcium and magnesium were significantly lower in
      schedules B and C versus A. PTH levels did not differ significantly. However, PTH
      changes during dialysis was -36.6+/-38.6%, 6.3+/-69.8% and 32.2+/-63.2% in A, B
      and C, respectively (p<0.05 A vs. C). A significant inverse correlation was found
      between total Ultrafiltration and postdialysis levels of total calcium (r:-0.56,
      p<0.001), ionized calcium (r:-0.65, p<0.001) and magnesium (r:-0.47, p<0.01). No
      differences were observed in pre and postdialysis phosphate levels, neither mass
      transfer and clearance of phosphate. We concluded that high ultrafiltration flow
      rates and substitution fluid without divalent cations induces a negative calcium
      and magnesium balance. These changes may stimulate PTH secretion during HDF. This
      technique did not resulted in a higher clearance or phosphate removal.

PMID- 18045036
TI  - [Calcific uraemic arteriolopathy (calciphylaxis): incidence, clinical features
      and long term outcomes].
AB  - Calcific uraemic arteriolopathy, also named calciphylaxis, is a rare but serious
      disorder characterized by medial mural calcification of small vessel leading to
      tissue ischaemia. It most commonly occurs in end stage renal disease patients on
      dialysis or recently received renal transplant with chronic nephropathy
      allograft. The pathogenesis of calciphylaxis is poorly understood. Abnormalities
      in mineral metabolism are clearly involved, but the specific factors that induces
      this disorder are not completely known. OBJECTIVES: Describe the main clinical
      features, outcomes and follow up of all calciphylaxis cases recorded in our
      dialysis unit in order to analyse the incidence, the main biologic parameters and
      the therapeutic background in which calciphylaxis appeared. MATERIAL AND METHODS:
      We performed a descriptive study about all the calciphylaxis cases diagnosed at
      our dialysis unit between the years 1991 and 2005. RESULTS: 8 cases, 6 women.
      Mean age: 65.3 years. All the patients were on haemodialysis treatment (one
      previous renal transplant). Mean time on dialysis was 76.6 months. Cumulative
      incidence was 1.17%. The principal end stage renal disease aethiology was
      neprhoangioeslerosis in four patients. Secondary hiperparatyrhoidism was present
      in 4 patients and 2 of them had been paratyrhoidectomized previously. A second
      cutaneous biopsy was needed for correct diagnosis in 3 patients. Calciphylaxis
      distal lesions were present in 7 patients. Two cases required urgent
      paratyrhoidectomy in order to control calciphylaxis. Only in 2 cases a Ca x P
      product > 60 mg/dL was present and 3 cases had PTHi values higher than 300 pg/mL.
      Calcium phosphate binders and vitamin D were present in 2 and 4 cases,
      respectively. One patient with proximal calciphylaxis died due to skin injury
      infection. CONCLUSIONS: Calciphylaxis is a rare disorder but not exceptional,
      related to end stage renal disease patients. The diagnosis requires a high
      clinical suspicion, being sometimes difficult to distinguish from other entities
      in spite of pathological study. Proximal distribution of calciphylaxis had worst
      prognostic. Metabolic disorders and therapeutics background were not different
      from other patients included in dialysis treatment.

PMID- 18045037
TI  - [Peritoneal dialyisis role in heart failure treatment, experience in our center].
AB  - Peritoneal dialysis is a renal replacement therapy indicated in patients with an
      unstable hemodynamic status. It has been used, by ultrafiltration, preferably in
      those patients with congestive heart failure refractory to conventional medical
      therapy. We present the experience of our center with five patients who were
      affected by severe congestive heart failure [Class IV on the New York Heart
      Association (NYHA) scale] and diverse stages of chronic renal failure, who
      received this therapy. Icodextrin has been used as an osmotic agent to induce
      ultrafiltration. The follow-up period ranged between 5 and 14 months (9.8 +/- 3.7
      months). The results that we have found are similar to those of other studies: we
      observed a significant improvement in quality of life and a reduction in
      morbidity and hospitalization rates in all our patients. But it seems to be
      necessary to make a prospective randomized controlled trial with more number of
      individuals to confirm these promising facts, to clarify the impact on the
      survival, and to analyze the cost-benefit for treating patients suffering from
      refractory, end stage congestive heart failure.

PMID- 18045038
TI  - [Oxidative stress analysis in patients on hemodiafiltration on-line].
AB  - Patients with chronic renal disease have a very high mortality due to
      cardiovascular disease. However, the traditional risk factors are not the only
      one explanation. Nowadays, there are new risk factors becoming, and one of these
      is the oxidative stress. Besides today we know that when these patients receive
      haemodialysis are being exposed to an additional oxidative stress. The aim of
      this study was to measure and to compare the degree of oxidative stress in two
      groups of patients on different dialysis techniques: a) On-Line
      Haemodiafiltration three times / week (OL-HDF). b) Daily Om-Line
      haemodiafiltration ( six times / week ) ( dOL-HDF) We studied 9 patients with
      chronic renal disease stage 5 on hemodialysis. They all were men, with a medium
      age of 72,5 +/- 6 years. Five patients were on dOL-HDFand four on tOL-HDF.
      Glutathione (GSH) concentration of patients on dOL-HDF before dialysis was 742+/-
      153 nmol/ml and post-dialysis de 878+/- 223. Blood GSSG concentration before and
      after dialysis was 34+/- 14 nmol/ml y 137+/- 74 nmol/ml (p< 0,03). GSSG/GSH ratio
      pre-dialysis was 58+/-10 and post-dialysis 169+/-65 ( p < 0,03). In OL-HDF group
      GSSG concentration and the ratio GSSG/GSH also increased in a significative way
      from 99+/-45 nmol/ml to 179+/-66 nmol/ml, and from 161+/- 99 to 337+/-143 (
      p<0,05). We also found differences in pCR concentrations between both groups; 3+/
      1,4 g/l in dOL-HDF and 8,75+/-5,8 g/l in HDF OL. (p< 0,05). We did not find
      differences between xatine-oxidase activity before and after hemodialysis and
      between groups. In conclusion, patient with terminal chronic renal disease on OL
      HDF receive an additional load of oxidative stress, as the increase in GSSG/GSH
      ratio in both groups shows. However patients on dHDF-OL shows low ratios GSSG/GSH
      post-hemodialysis and low pCR concentrations, and maybe this could be explained
      because daily on line haemodiafiltration improves purification of inflammatory
      mediators. Clue words: Hemodialysis, oxidative stress, glutathione, gssg/gsh
      ratio, xantine oxidasa.

PMID- 18045039
TI  - [Health related quality of life evolution in kidney transplanted patients].
AB  - OBJECTIVE: We analyzed the evolution in the Health Related Quality of Life
      (HRQOL) during the first year following renal transplant. METHODS: Prospective
      and longitudinal study carried out with 28 patients who received a primary
      cadaveric renal transplant. The tests applied were a structured interview and SF
      36, Euroqol- 5D (EQ-5D) Health Questionnaires and End-Stage Renal Disease Symptom
      Checklist- Transplantation Module (ESRD-SCL). RESULTS: With the course of time,
      the renal patients improve in four areas: physical (<<physical functioning>> and
      <<cardiac and renal malfunction>>), psychological (<<vitality>> and <<mental
      health>>), execution of daily tasks (<<limitations in role in order to physical
      problems>> and <<daily tasks>>) and subjective perception of own state of health
      (<<current health>>). CONCLUSIONS: The HRQOL in renal transplant patients
      improves with the course of time.

PMID- 18045040
TI  - [Evolutive prediction indicators in primary immunoglobulin A nephropathy. Cuban
      Cooperative Study].

PMID- 18045041
TI  - [Renal involvement by AA amyloidosis in inclusion body myositis].
AB  - Inclusion body myositis is currently considered a variant of adult inflammatory
      myopathies. Clinical course is insidious and besides typical proximal muscles
      disorder, extension to distal ones is found in up to 95% of cases. Mean survival
      ranges from 3 to 5 years. Infections are the first death cause, secondary to
      existing disability a few years after diagnosis. Chronic rheumatic diseases
      related amyloidosis has became the most frequent kind of reactive amyloidosis or
      AA amyloidosis. Clinical manifestations of AA amyloidosis mainly affect the
      kidney. We present the case of a woman with Inclusion body myositis and renal
      involvement by AA amyloidosis. In our review of literature we haven t found any
      article relating AA amyloidosis with idiopathic inflammatory myopathies of the
      adult, what would turn this case into the first ever reported. We can probably
      find the reason in the bad prognosis of this entity. So we propose making a renal
      biopsy to all those patients with a long lasting rheumatologic disease and
      unexpected impaired renal function.

PMID- 18045042
TI  - [Secondary amyloidosis (AA-type) due to localized cutaneous vasculitis].
AB  - We report a case of a 49 year old man, diagnosed soon after the outcome of casual
      proteinuria, of AA-type amyloidosis in relation to small and medium vessel
      cutaneous vasculitis without systemic involvement. This combination is a rare
      entity and only two cases of cutaneous hypersensibility vasculitis complicated
      with AA-type amyloidosis had been reported. We describe the results of the use of
      several immunosuppressive drugs during four years follow up with temporally total
      remission of the disease.

PMID- 18045043
TI  - [Adverse reactions to polysulphone membrane dialyzers durind hemodialysis].
AB  - The majority of severe hypersensitivity reactions in hemodialysis (HD) patients
      has been due to sensitization to ethylene oxide or to non-biocompatible membrane
      dialyzers like cupramonium membrane. However could be the possibility of adverse
      reactions with other hemodialysis substances. Adverse reactions with
      biocompatible polisulphone membranes are not frequent, but some authors described
      anaphilactoid reactions related to them. Any severe clinical syndrome of
      broncoespasm during hemodialysis with several biocompatible polysulphone
      membranes made by different manufacturers and with a variety of sterilization
      methods is presented here. The following day he was dialyzed on an cellulose
      triacetate dialyzer and the hemodialysis treatment was uneventful. This cas
      report demonstrates the complex nature involving a hypersensitivity reaction to
      HD.

PMID- 18045044
TI  - [Unknown origin fever and acute renal failure].

PMID- 18045045
TI  - [The recurrence of vasculitis in the renal transplant treatment with Rituximab].

PMID- 18045046
TI  - [Membranous nephropathy presenting as microscopic hematuria].

PMID- 18045047
TI  - [Norfloxacin-induced acute interstitial nephritis].

PMID- 18045048
TI  - [Posterior reversible encephalopathy syndrome (PRES) and chronic kidney disease].
AB  - Posterior reversible encephalopathy (PRES) is a recently described syndrome,
      defined by clinical and neuroimaging features. Chronic kidney disease patients
      may be especially vulnerable to this syndrome because they are frequently exposed
      to several of its possible causes, including uremia and hypertension. In its most
      severe form, PRES can manifest clinically as seizures, coma or death. However, if
      properly diagnosed and treated, this syndrome can be completely reversible.
      Therefore, neuroimaging methods, especially brain magnetic resonance is
      fundamental for its diagnosis because it shows brain edema in characteristic
      pattern, and excludes causes of seizures or coma. An important example is the
      case of a young hypertensive chronic kidney disease patient on peritoneal
      dialysis, brought to the emergency room comatous with generalized tonic-clonic
      seizures; the cerebral magnetic resonance imaging features were impressive. Anti
      hypertensive therapy and hemodialysis allowed complete recovery. The
      reversibility of this syndrome depends on timely diagnosis and therapy and
      therefore it should be kept in mind in the differential diagnosis of seizures. or
      coma in chronic kidney disease patients.

PMID- 18045049
TI  - [Prostatic carcinoma as acute renal failure of unknown etiology].

PMID- 18045050
TI  - [Segmental and focal hyalinosis secondary to gastric adenocarcinoma].

PMID- 18045051
TI  - [Pancytopenia as adverse event due to enalapril and glipizide on renal failure].

PMID- 18045052
TI  - [HTA and peritoneal dialysis].

PMID- 18045053
TI  - [Adaptative disorder with dermatozoic hallucinations in a patient on
      hemodialysis].

PMID- 18045054
TI  - Non-receptor tyrosine kinases as molecular targets for patient tailored cancer
      therapy.

PMID- 18045055
TI  - Oncogenic fusion tyrosine kinases as molecular targets for anti-cancer therapy.
AB  - Deregulated activation of protein tyrosine kinases (PTKs) is a frequent event
      underlying malignant transformation in many types of cancer. The formation of
      oncogenic fusion tyrosine kinases (FTKs) resulting from genomic rearrangements,
      represents a common mechanism by which kinases escape the strict controls that
      normally regulate their expression and activation. FTKs are typically composed of
      an N-terminal dimerisation domain, provided by the fusion partner protein, fused
      to the kinase domain of receptor or non-receptor tyrosine kinases (non-RTKs).
      Since FTKs do not contain extracellular domains, they share many characteristics
      with non-RTKs in terms of their properties and approaches for therapeutic
      targeting. FTKs are cytoplasmic or sometimes nuclear proteins, depending on the
      normal distribution of their fusion partner. FTKs no longer respond to ligand and
      are instead constitutively activated by dimerisation induced by the fusion
      partner. Unlike RTKs, FTKs cannot be targeted by therapeutic antibodies, instead
      they require agents that can cross the cell membrane as with non-RTKs. Here we
      review the PTKs known to be expressed as FTKs in cancer and the strategies for
      molecularly targeting these FTKs in anti-cancer therapy.

PMID- 18045056
TI  - Targeting JAK3 tyrosine kinase-linked signal transduction pathways with
      rationally-designed inhibitors.
AB  - Inhibitors of Janus Kinase 3 (JAK3) show potential as a new class of apoptosis
      inducing anti-cancer drugs. In addition, JAK3 inhibitors may also be useful as
      immunosuppressive agents. Rationally designed selective inhibitors of JAK3 such
      as JANEX-1, that do not inhibit other Janus kinases have recently undergone
      extensive preclinical testing that revealed a favorable pharmacodynamic profile.
      Here we discuss the clinical potential of targeting JAK3-linked signal
      transduction pathways with small molecule inhibitors such as JANEX-1.

PMID- 18045057
TI  - Bruton's tyrosine kinase as a new therapeutic target.
AB  - Targeting Bruton's tyrosine kinase (BTK) with a small molecule inhibitor may be
      useful in treatment of BTK-expressing malignancies because of the anti-apoptotic
      function of BTK in cancer cells. Furthermore, BTK inhibitors also exhibit anti
      thrombotic properties that may be desirable in the context of the increased risk
      of thromboembolic complications in cancer patients. This review will focus on the
      role of BTK in drug resistance in cancer, thromboembolism, and various pathologic
      immune responses, such as graft versus host disease. The therapeutic potential of
      targeting BTK is illustrated by discussion of the biologic activity profile of
      the rationally designed BTK inhibitor LFM-A13.

PMID- 18045058
TI  - Non-receptor tyrosine kinase inhibitors in lung cancer.
AB  - Lung cancer is a leading cause of cancer death. Systemic therapies with cytotoxic
      chemotherapies remain ineffective. Current research efforts in lung cancer have
      focused on developing novel agents to target cellular pathways that are altered
      in lung cancer. Protein tyrosine kinases are a family of oncogenes that regulate
      important cellular processes such as differentiation, proliferation, cell cycle,
      motility, and apoptosis. In this article, we review non receptor tyrosine
      kinases' role in lung cancer and the development of agents that target these
      proteins.

PMID- 18045059
TI  - Jak2 tyrosine kinase and cancer: how good cells get HiJAKed.
AB  - Cloned in 1992, Jak2 tyrosine kinase has emerged as a critical molecule in
      mammalian development, physiology, and disease. Here, we will review the early
      history of Jak2 as it pertains to its role in classical cellular signaling. We
      also review how specific structural determinants within Jak2 dictate its overall
      function. Finally, we will review relatively recent literature as it pertains to
      the role of Jak2 in neoplastic growth as well as the identification of novel Jak2
      inhibitors. It is our hope that by reviewing these specific areas, we will have a
      better understanding of the role of Jak2 in cancer, and in turn, we may have a
      better idea as to how to block aberrant Jak2 function.

PMID- 18045060
TI  - SRC family nonreceptor tyrosine kinases as molecular targets for cancer therapy.
AB  - The Src family of kinases has nine known members, all of which are nonreceptor
      tyrosine kinases involved in signal transduction in both normal and cancer cells.
      Interest in these kinases has increased recently because of the development,
      initial clinical success, and low toxicity of pharmacologic inhibitors. c-Src is
      the best-studied member of the Src family and the one most often implicated in
      cancer progression. c-Src has multiple substrates that lead to diverse biologic
      effects, including changes in proliferation, motility, invasion, survival, and
      angiogenesis. c-Src has been most extensively studied in colon cancer where
      correlative and direct experimental evidence has shown that it mediates several
      aspects of cancer cell progression. c-Src has a similar role in multiple tumor
      types, including pancreatic cancer, breast cancer, lung cancer, head and neck
      squamous cell carcinoma, and prostate cancer. Several inhibitors of the Src
      family kinases are in clinical development; three are currently being studied in
      clinical trials. Initial data from these trials suggest that these agents are
      well tolerated. Future clinical development of these inhibitors will include
      trials in patients with solid tumors and of combination therapy.

PMID- 18045061
TI  - Synthetic SRC-kinase domain inhibitors and their structural requirements.
AB  - Protein tyrosine kinases catalyze the transfer of phosphoryl groups from ATP to
      amino acids on proteins and play a fundamental role in signal transduction
      pathways in mammalian cells. In particular, Src and Src-family are non-receptor
      tyrosine kinases that regulate cell growth, differentiation, migration, adhesion
      and apoptosis. Src-family members share common features, with well defined
      domains. The activation of these enzymes in response to a variety of stimuli
      leads from a close and inactive conformation to an open and active one, through a
      balance of phosphorylation and dephosphorylation of the enzyme structure,
      characterized in different cases by x-ray crystallography. Overexpression,
      deregulation or mutations of these enzymes have been observed and studied in many
      diseases, first of all in many human malignancies, such as colon, breast,
      pancreatic and other cancers. Src-family is also involved in other pathologic
      situations, such as osteoporosis, cardiovascular diseases, immune system
      disorders, and, recently, it has been also demonstrated the involvement of Src in
      prion diseases. Therefore, Src-family is an attractive and fundamental target for
      the design of new therapeutic agents against different pathologies, in particular
      cancer and bone diseases. Currently, there is no approved drug acting as Src
      kinase inhibitor, but new molecules, very potent and selective toward this family
      of kinases and also in vivo, are continuously synthesized, as demonstrated by the
      high number of publications and patents in this field. Here, we report several
      examples of Src kinase domain inhibitors, focusing our attention on chemical
      structures, structure-activity relationships and mechanism of action.

PMID- 18045062
TI  - Role of focal adhesion kinase in human cancer: a potential target for drug
      discovery.
AB  - The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes
      to the points of cell contact with the extracellular matrix, called focal
      adhesions. FAK is involved in several cellular processes including invasion,
      motility, proliferation and apoptosis. In in vivo animal studies, FAK has been
      shown to contribute to tumor development and malignancy. Furthermore, FAK
      expression was shown to be elevated in a number of human cancers. Increased FAK
      expression and activity are correlated with malignant phenotype and poor
      prognosis in patients. Taken together, these studies suggest that FAK is a
      potentially good target for drug discovery. In this review, FAK and its
      relationship to cancer, as well as approaches to therapeutic intervention of FAK
      will be discussed.

PMID- 18045063
TI  - Synthesis and structure-activity relationships of potent antitumor active
      quinoline and naphthyridine derivatives.
AB  - The disease of cancer has been ranked second after cardiovascular diseases and
      plant-derived molecules have played an important role for the treatment of
      cancer. Nine cytotoxic plant-derived molecules such as vinblastine, vincristine,
      navelbine, etoposide, teniposide, taxol, taxotere, topotecan and irinotecan have
      been approved as anticancer drugs. Recently, epothilones are being emerging as
      future potential anti-tumor agents. However, targeted cancer therapy has now been
      rapidly expanding and small organic molecules are being exploited for this
      purpose. Amongst target specific small organic molecules, quinazoline was found
      as one of the most successful chemical class in cancer chemotherapy as three
      drugs namely Gefitinib, Erlotinib and Canertinib belong to this series. Now,
      quinazoline related chemical classes such as quinolines and naphthyridines are
      being exploited in cancer chemotherapy and a number of molecules such as
      compounds EKB-569 (52), HKI-272 (78) and SNS-595 (127a) are in different phases
      of clinical trials. This review presents the synthesis of quinolines and
      naphthyridines derivatives, screened for anticancer activity since year 2000. The
      synthesis of most potent derivatives in each prototype has been delineated. A
      brief structure activity relationship for each prototype has also been discussed.
      It has been observed that aniline group at C-4, aminoacrylamide substituents at C
      6, cyano group at C-3 and alkoxy groups at C-7 in the quinoline ring play an
      important role for optimal activity. While aminopyrrolidine functionality at C-7,
      2'-thiazolyl at N-1 and carboxy group at C-3 in 1,8-naphthyridine ring are
      essential for eliciting the cytotoxicity. This review would help the medicinal
      chemist to design and synthesize molecules for targeted cancer chemotherapy.

PMID- 18045065
TI  - Pathobiology of head and neck squamous tumorigenesis.
AB  - Head and neck squamous epithelial carcinogenesis is a complex multistep process
      that entails a progressive acquisition of alterations in diverse vital cellular
      pathways. The nature of these alterations and the order of their occurrence have
      remained unresolved. In the past 15 years, the thrust of research in this field
      has centered on the epithelial genetic and/or epigenetic changes attendant to
      their development and progression. Little efforts, however, have been expended on
      changes in structural or host microenvironment and their role in these tumors.
      Only recently has the latter topic become the focus of attention. This review
      will address recent advances in both cellular and structural findings in head and
      neck squamous carcinoma development and progression. Targeting these events for
      biological and therapeutic approaches is a desirable goal for future effective
      treatment of patients with this cancer.

PMID- 18045066
TI  - Exploration of metastasis-related proteins as biomarkers and therapeutic targets
      in the treatment of head and neck cancer.
AB  - Head and neck (HN) cancer is a significant health-care problem worldwide. One of
      the major prognostic factors for squamous cell carcinomas of the head and neck
      (HNSCC) is metastasis. Early detection of lymph node metastasis and the
      identification of key protein targets for the treatment of metastatic HNSCC
      remain a challenge in current cancer research. Recent developments in molecular
      analysis technologies, such as DNA microarray and proteomic analyses, have
      provided powerful tools for the detection of metastatic signatures in primary
      tumors, opening new avenues toward the molecular diagnosis and prognosis of HN
      cancers. Evaluation of gene expression profiling identified in metastatic
      signatures has further facilitated the understanding of HNSCC metastasis at the
      molecular level. This review will focus on current exploration of metastatic
      proteins in HNSCC with an emphasis on molecular signatures of metastatic HNSCC in
      order to understand the functions of metastasis-related proteins involved in
      adhesion, invasion, dissemination, and survival, and to define appropriate
      biomarkers and targets for the treatment of this disease.

PMID- 18045067
TI  - Current status and future perspectives of chemoprevention in head and neck
      cancer.
AB  - The incidence of SCCHN is expected to be approximately 42,800 new cases in the
      United States with more than 12,000 deaths from this disease for the year 2006.
      The five-year survival rate for patients with SCCHN in the United States and
      other developed countries is still poor, approximately 40%, and even those
      patients who do not experience recurrence of the original cancer, have a high
      risk of developing a second primary malignancy. Thus, a preventative approach
      before the development of invasive cancer is highly desirable and novel
      strategies to reduce cancer incidence in SCCHN and other tobacco-carcinogen
      related malignancies are being pursued. Ever since the last two decades have seen
      the rise and fall of the results of clinical trials using carotinoids and
      retinoids as chemopreventive agents, new treatment strategies are needed.
      Selective and nonselective COX-1/2 inhibitors and EGFR tyrosine kinase inhibitors
      have shown promising results in cancer therapy and are currently evaluated in
      chemoprevention trials. However, associated high costs and side effects make
      these less attractive to patients with premalignant lesions. Phytochemical
      containing foods like green tea, pomegranate juice and other natural compounds
      are attractive since they are less costly, nontoxic and widely available. While
      small trials have shown promising results using these agents, larger trials have
      yet to be conducted to establish chemopreventive effects. Since premalignant
      lesions of the oral cavity are easily accessible for topical treatments, it
      remains to be seen if there is a role for topical treatments. Current clinical
      trials using these novel agents for prevention of second primary tumors or
      treatment of premalignant lesions will further elucidate which agents should be
      used but also will help to establish the role of chemoprevention in head and neck
      cancer.

PMID- 18045068
TI  - Anti-tumor vaccines in head and neck cancer: targeting immune responses to the
      tumor.
AB  - Immune therapies aiming at the destruction of a residual tumor and inducing tumor
      specific memory responses are gaining acceptance among clinicians treating head
      and neck squamous cell carcinoma (HNSCC). This solid tumor lends itself
      remarkably well to currently popular vaccination strategies. Immune suppression
      is a hallmark of HNSCC, and its reversal accompanied by the vaccine-mediated
      restoration of antitumor immunity might be a promising approach to achieving
      improved survival of HNSCC patients. To date, few antitumor vaccines for HNSCC
      have been clinically evaluated. The reasons for this slow start are discussed,
      and the ongoing phase I clinical vaccination trials for HNSCC patients are
      briefly described. The emphasis is on dendritic cell (DC)-based vaccines, largely
      because of enhanced immunogenicity of epitopes presented by adoptively
      transferred DC to responder T cells in vivo. Delivery of such antitumor vaccines
      in combination with conventional therapies and in the setting of a minimal
      residual disease to HNSCC patients takes advantage of exquisite specificity of
      the immune system at the time when tumor-induced suppression is reduced. Vaccine
      driven generation, long-term survival and maintenance of tumor-specific immune
      cells are the objectives that antitumor vaccines have to realize to be clinically
      beneficial in HNSCC.

PMID- 18045069
TI  - Targeting angiogenesis in head and neck cancer.
AB  - In the early 1970s, the hypothesis that tumor growth is dependent on angiogenesis
      was first established [1]. Since then, the role played by blood vessels in tumor
      growth and progression has been extensively studied and debated. Preclinical
      evidence strongly suggests that VEGF plays a role in promoting the growth and
      progression of disease in various tumor types including squamous cell carcinoma
      of the head and neck (SCCHN), of which close to 38,500 new cases are diagnosed
      each year. In SCCHN, the role of anti-angiogenic therapy has yet to be defined.
      Traditional therapy of SCCHN has involved a multimodality approach with
      radiotherapy, surgery as well as chemotherapy. More recently, novel therapeutic
      agents have been subject to preclinical and clinical development, among which
      anti-angiogenic therapy has gained much recent interest. In this critical review,
      we give an overview of angiogenesis and its potential therapeutic targets, and we
      focus on its preclinical and clinical applications in SCCHN.

PMID- 18045070
TI  - EGFR-targeting monoclonal antibodies in head and neck cancer.
AB  - The epidermal growth factor (EGFR) and its receptor were discovered nearly 40
      years ago. Over the past decade interruption of this pathway has been exploited
      in the treatment of various solid tumors. Antibodies that interfere with ligand
      binding to and dimerization of the EGFR (and small molecules that inhibit the
      EGFR tyrosine kinase) are anti-proliferative, profoundly radiosensitizing, and
      synergistic with DNA-damaging cytotoxic agents. Proposed mechanisms of radio- and
      chemosensitization include enhanced apoptosis, interference with DNA repair and
      angiogenesis, receptor depletion from the cell surface and antibody-dependent
      cell-mediated cytotoxicity. This article provides a reader with a comprehensive
      review of EGFR-targeting antibodies under development for the treatment of head
      and neck squamous cell cancer (HNSCC) and also summarizes relevant clinical data
      in this disease with small molecule EGFR inhibitors. One of the monoclonal
      antibodies, cetuximab, recently received full FDA approval for the treatment of
      patients with locally advanced (with radiation) or metastatic HNSCC (as a single
      agent). Regulatory approval followed reporting of a large international study in
      which the addition of cetuximab to definitive radiation therapy in HNSCC resulted
      in statistically significant improvements in locoregional control and overall
      survival. Results of the pivotal trial, other clinical data supporting the
      regulatory approval, and a preview of the next generation of clinical trials are
      presented. Considerable work remains to be done, particularly to enhance our
      understanding of factors that may predict for favorable response to EGFR
      inhibitor therapy and to evaluate the impact of integrating anti-EGFR therapies
      into complex chemoradiation programs delivered with curative intent.

PMID- 18045071
TI  - Treatment of squamous cell carcinoma of the head and neck in the metastatic and
      refractory settings: advances in chemotherapy and the emergence of small molecule
      epidermal growth factor receptor kinase inhibitors.
AB  - Approximately 475,000 cases of squamous cell carcinoma (SCCHN) of the head and
      neck occur worldwide. Whereas significant advances have been made in the
      treatment of early and locally advanced disease, the prognosis for recurrent and
      metastatic (R/M) disease remains poor. Compounds with demonstrated activity
      include cisplatin and carboplatin, antimicrotubular compounds such as taxanes and
      vinorelbine, and fluoropyrimidines. In refractory and metastatic disease,
      regimens combining platinum agents with taxanes or fluorouracil based agents
      produce a 30% response rate and a median overall survival of six to eight months.
      Newer three agent chemotherapy regimens have produced response rates in the range
      of 40-50%, without significant improvements in overall survival noted. Recently,
      a new class of medications targeting signal transduction pathways has come into
      focus in the treatment of various malignancies. In SCCHN, given the high
      prevalence of expression of the epidermal growth factor receptor (EGFR) and its
      role in promoting cellular growth and proliferation, molecules targeting the
      receptor's intracellular kinase domain are a logical strategy. The agents
      gefitinib and erlotinib have yielded response rates in the 5-15% range when used
      as single agents. In addition, newer agents with broad activity against the EGFR
      and other related erbB receptor family members are being developed in clinical
      trials. Strategies to enhance the activity of EGFR tyrosine kinase inhibitors
      (TKIs) in treating SCCHN are being investigated, as well as strategies to select
      individuals with tumors more likely to respond to these drugs. This article
      reviews the advances that have made in treating refractory and metastatic
      disease, with particular focus on the challenges that are faced in successfully
      translating EGFR inhibition as a paradigm of tumor treatment in SCCHN.

PMID- 18045072
TI  - Recent advances in combined modality therapy for locally advanced head and neck
      cancer.
AB  - Half of all patients with squamous cell carcinoma of the head and neck (SCCHN)
      present with locally advanced disease. Despite the development of new treatment
      strategies, mortality rates have only improved over the last decade by 2.6% per
      year, and prognosis remains poor. Combined modality therapy offers the potential
      for organ preservation, particularly for tumors arising in the larynx,
      hypopharynx and oropharynx. Organ preservation with concurrent chemoradiotherapy
      (CRT) was first established in laryngeal carcinoma. Recent results of the
      laryngeal study, RTOG 9111, indicate that even though larynx preservation is
      improved with CRT compared to induction chemotherapy followed by radiotherapy
      alone, laryngectomy-free survival is the same. Future attentions should be
      focused not only on improving treatment efficacy, but also on efforts to minimize
      the long term toxicities of therapy for SCCHN, particularly because long term
      toxicities not only diminish quality of life, but seem to impact on survival. In
      the future, targeted therapies may be incorporated into combined modality therapy
      for SCCHN, offering the chance to enhance the anticancer effects of treatment
      without increasing toxicity. Improvements in radiotherapy techniques may also
      move the field forward. Finally, there is renewed interest in the role of
      induction chemotherapy as part of a sequential treatment approach for advanced
      SCCHN. If the current generation of studies evaluating sequential therapy is
      favorable, future studies incorporating targeted therapies into this platform
      will offer further potential for advancing the treatment of SCCHN.

PMID- 18045073
TI  - Recent approaches in chemoprevention of prostate cancer.
AB  - In highly developed countries like USA, approximately one out of 6 in the male
      population will expect to have prostate cancer in their life time.
      Chemoprevention is presumably one of most effective means to combat many types of
      cancer including prostate cancer (PCa). Because clinically significant PCa
      usually requires more than a decade to develop, therefore, it would be an ideal
      target for chemoprevention. This review will focus on recent findings of the most
      studied, naturally occurring, synthetic or semi-synthetic chemicals for potential
      use in preventing PCa. Newly discovered chemicals which show potential in
      preventative or therapeutic effects will be included. Molecular mechanisms and
      gene/pathway targets by which the above agents act on target cells will be
      briefly discussed. The recent findings on the chemicals possessing anti-androgen
      receptor, anti-DNA methyltransferase, or anti-histone deacetyltransferase
      activity will also be presented. It will further present some important issues
      regarding how the interactions of chemopreventing agents with genetic
      polymorphisms or epigenetic factors might affect anti-cancer effects of the
      agents. Related large trials, if appropriate, will also be discussed.

PMID- 18045074
TI  - Targeting MDM2 and MDMX in retinoblastoma.
AB  - Retinoblastoma is the third most common form of cancer in infants, and metastatic
      retinoblastoma is lethal in approximately 90% of cases. Early detection and
      aggressive therapy has resulted in a 95% probability of survival for
      retinoblastoma patients in the United States. However, the United States only
      represents 3-4% of the retinoblastoma cases worldwide. The majority of children
      diagnosed with retinoblastoma each year live in developing countries where the
      probability of survival is closer to 50%. This difference in survival rates
      reflects poor early detection rates and limited resources for the aggressive
      therapy necessary to treat retinoblastoma and manage the side effects associated
      with broad-spectrum systemic chemotherapy in young children. In order to have the
      most significant impact on retinoblastoma treatment in the United States and
      worldwide, current efforts have focused on local delivery of targeted
      chemotherapy. In this review, we summarize recent data showing that the p53
      pathway is inactivated in 75% of retinoblastoma patients due to extra copies of
      the MDM2 and MDMX genes. A small molecule inhibitor of MDM2 called nutlin-3 can
      induce p53-mediated cell death in retinoblastoma cells. Subconjunctival delivery
      of nutlin-3 in preclinical models of retinoblastoma confirmed the efficacy of
      this approach in vivo. The advantage of local application of targeted
      chemotherapeutic agents such as nutlin-3 is that greater intraocular drug
      concentrations can be achieved without the side effects associated with systemic
      broad-spectrum chemotherapy. We propose that subconjunctival administration of
      targeted chemotherapy may be the best treatment option for children with
      retinoblastoma in the United States and throughout the developing world because
      it provides greater tumor response without the costs and complications associated
      with current treatment protocols.

PMID- 18045076
TI  - Yeast genomics and drug target identification.
AB  - The budding yeast Saccharomyces cerevisiae is well recognized as a preferred
      eukaryote for the development of genomic technologies and approaches.
      Accordingly, a sizeable complement of genomic resources has been developed in
      yeast, and this genomic foundation is now informing a wide variety of
      disciplines. In particular, yeast genomic methodologies are gaining an expanding
      foothold in drug development studies, most notably as a preliminary tool towards
      drug target identification. In this review, we highlight many applications of
      yeast genomics in the identification of targeted genes and pathways of small
      molecules or therapeutic drugs. The applicability of genome-wide resources of
      yeast disruption and deletion mutants for drug-sensitivity/resistance screening
      is presented here, along with a summary of microarray technologies for drug-based
      transcriptional profiling and synthetic interaction mapping. Applications of
      protein-interaction traps for potential drug target identification are also
      considered. Collectively, this overview of yeast genomics emphasizes the growing
      intersection between high-throughput model organism biology and medicinal
      chemistry an intersection promising tangible advances for both academic and
      pharmaceutical fields alike.

PMID- 18045077
TI  - Stem cells and combinatorial science.
AB  - Stem cell-based technologies have the potential to help cure a number of cell
      degenerative diseases. Combinatorial and high throughput screening techniques
      could provide tools to control and manipulate the self-renewal and
      differentiation of stem cells. This review chronicles historic and recent
      progress in the stem cell field involving both pluripotent and multipotent cells,
      and it highlights relevant cellular signal transduction pathways. This review
      further describes screens using libraries of soluble, small-molecule ligands, and
      arrays of molecules immobilized onto surfaces while proposing future trends in
      similar studies. It is hoped that by reviewing both the stem cell and the
      relevant high throughput screening literature, this paper can act as a resource
      to the combinatorial science community.

PMID- 18045078
TI  - Chemical genomic and proteomic methods for determining kinase inhibitor
      selectivity.
AB  - The clinical success of the Bcr-Abl tyrosine kinase inhibitor Gleevec((R)) and
      the recent clinical approval of a number of small molecule drugs that target
      protein kinases have intensified the search for novel protein kinase inhibitors.
      Since most small molecule kinase inhibitors target the highly conserved ATP
      binding pocket of this enzyme family, the target selectivity of these molecules
      is a major concern. Due to the large size of the human kinome, it is a formidable
      challenge to determine the absolute specificity of a given protein kinase
      inhibitor, but recent technological developments have made substantial progress
      in achieving this goal. This review summarizes some of the most recent
      experimental techniques that have been developed for the determination of protein
      kinase inhibitor selectivity. Special emphasis is placed on the results of these
      screens and the general insights that they provide into kinase inhibitor target
      selectivity.

PMID- 18045079
TI  - Chemical control over protein-protein interactions: beyond inhibitors.
AB  - Protein-protein interactions have become attractive drug targets and recent
      studies suggest that these interfaces may be amenable to inhibition by small
      molecules. However, blocking specific interactions may not be the only way of
      manipulating the extensive network of interacting proteins. Recently, several
      approaches have emerged for promoting these interactions rather than inhibiting
      them. Typically, these strategies employ a bifunctional ligand to simultaneously
      bind two targets, forcing their juxtaposition. Chemically "riveting" specific
      protein contacts can reveal important aspects of regulation, such as the
      consequences of stable dimerization or the effects of prolonged dwell time.
      Moreover, in some cases, entirely new functions arise when two proteins, which
      normally do not interact, are brought into close proximity with one another.
      Together with inhibitors, bifunctional molecules are part of a growing toolbox of
      chemical probes that can be used to reversibly and selectively control the
      interact-ome. Using these reagents, new insights into the dynamics of protein
      protein interactions and their importance in biology are beginning to emerge.
      Future hurdles in this area lie in the development of robust synthetic platforms
      for rapidly generating compounds to meet the challenges of diverse protein
      protein interfaces.

PMID- 18045080
TI  - Functional genomics and NMR spectroscopy.
AB  - The recent success of the human genome project and the continued accomplishment
      in obtaining DNA sequences for a vast array of organisms is providing an
      unprecedented wealth of information. Nevertheless, an abundance of the proteome
      contains hypothetical proteins or proteins of unknown function, where high
      throughput approaches for genome-wide functional annotation (functional genomics)
      has evolved as the necessary next step. Nuclear magnetic resonance spectroscopy
      is playing an important role in functional genomics by providing information on
      the structure of protein and protein-ligand complexes, from metabolite
      fingerprinting and profiling, from the analysis of the metabolome, and from
      ligand affinity screens to identify chemical probes.

PMID- 18045081
TI  - Functional nucleic acids in high throughput screening and drug discovery.
AB  - In vitro selection can be used to generate functional nucleic acids such as
      aptamers and ribozymes that can recognize a variety of molecules with high
      affinity and specificity. Most often these recognition events are associated with
      structural alterations that can be converted into detectable signals. Several
      signaling aptamers and ribozymes constructed by both design and selection have
      been successfully utilized as sensitive detection reagents. Here we summarize the
      development of different types of signaling nucleic acids, and approaches that
      have been implemented in the screening format.

PMID- 18045082
TI  - Applications of protein microarray technology.
AB  - Protein microarrays, an emerging class of proteomic technologies, are quickly
      becoming essential tools for large-scale and high throughput biochemistry and
      molecular biology. Recent progress has been made in all the key steps of protein
      microarray fabrication and application, such as the large-scale cloning of
      expression-ready prokaryotic and eukaryotic ORFs, high throughput protein
      purification, surface chemistry, protein delivery systems, and detection methods.
      Two classes of protein microarrays are currently available: analytical and
      functional protein microarrays. In the case of analytical protein microarrays,
      well-characterized molecules with specific activity, such as antibodies, peptide
      MHC complexes, or lectins, are used as immobilized probes. These arrays have
      become one of the most powerful multiplexed detection platforms. Functional
      protein microarrays are being increasingly applied to many areas of biological
      discovery, including drug target identification/validation and studies of protein
      interaction, biochemical activity, and immune responses. Great progress has been
      achieved in both classes of protein microarrays in terms of sensitivity and
      specificity, and new protein microarray technologies are continuing to emerge.
      Finally, protein microarrays have found novel applications in both scientific
      research and clinical diagnostics.

PMID- 18045083
TI  - Chemogenomic data analysis: prediction of small-molecule targets and the advent
      of biological fingerprint.
AB  - Chemogenomics comprises a systematic relationship between targets and ligands
      that are used as target modulators in living systems such as cells or organisms.
      In recent years, data on small molecule-bioactivity relationships have become
      increasingly available, and consequently so have the number of approaches used to
      translate bioactivity data into knowledge. This review will focus on two aspects
      of chemogenomics. Firstly, in cases such as cell-based screens, the question of
      which target(s) a compound is modulating in order to cause the observed phenotype
      is crucial. In silico target prediction tools can suggest likely biological
      targets of small molecules via data mining in target-annotated chemical
      databases. This review presents some of the current tools available for this task
      and shows some sample applications relevant to a pharmaceutical industry setting.
      These applications are the prediction of false-positives in cell-based reporter
      gene assays, the prediction of targets by linking bioassay data with protein
      domain annotations, and the direct prediction of adverse reactions. Secondly, in
      recent years a shift from structure-derived chemical descriptors to biological
      descriptors has occurred. Here, the effect of a compound on a number of
      biological endpoints is used to make predictions about other properties, such as
      putative targets, associated adverse reactions, and pathways modulated by the
      compound. This review further summarizes these "performance" descriptors and
      their applications, focusing on gene expression profiles and high-content
      screening data. The advent of such biological fingerprints suggests that the
      field of drug discovery is currently at a crossroads, where single target
      bioassay results are supplanted by multidimensional biological fingerprints that
      reflect a new awareness of biological networks and polypharmacology.

PMID- 18045085
TI  - Recognition of lysine residues on protein surfaces using calixarenes and its
      application.
AB  - A macrocyclic calix[6]arene carboxylic acid derivative is found to extract lysine
      rich protein cytochrome c from aqueous media into organic media through the
      complexation between the calixarene molecules and lysine residues on the surface
      of the protein. This article summarizes both the mechanism of protein extraction
      by the calixarene as well as the potential applications of the extraction
      process. The extraction process can be used for the purification of proteins
      through selective extraction and back-extraction under optimized conditions. On
      the other hand, the extracted protein exhibits enzymatic activity in organic
      media. The formation of a supramolecular complex by recognizing the residues on a
      protein surface can be construed as a novel recognition and/or modification
      method for biomacromolecules.

PMID- 18045086
TI  - Surface photochemistry: organic molecules within nanocavities of calixarenes.
AB  - In order to gain more information regarding photochemical processes in
      heterogeneous environments (opaque or powdered samples) laser induced time
      resolved luminescence and diffuse reflectance transient absorption spectroscopies
      were used for the study of benzophenone (and other neutral organic molecules) as
      guests and p-tert-butylcalix[n]arenes with n = 4, 6 and 8 (H(n)CLX[n]) and
      partially or totally O-propylated p-tert-butylcalix[4]arenes (H(n)Pr(m)CLX[4], n
      = 2, 1 and 0; m = 2, 3 and 4, respectively) were used as hosts. One of the main
      conclusions was that the solid support can deeply affect or even control the
      photochemistry of an adsorbed probe. A simple new methodology for lifetime
      distribution analysis of the decay of the probes included into calixarenes and
      other nanocavities was applied with success for decay data obtained with the use
      of intensified charge couple devices, i.e. intensified charge couple devices,
      ICCDs. Diffuse reflectance laser flash photolysis and gas chromatography - mass
      spectrometry techniques also provided complementary information, the former about
      transient species and the latter regarding the final products formed after light
      absorption.

PMID- 18045087
TI  - Design, synthesis and potent pharmaceutical applications of glycodendrimers: a
      mini review.
AB  - Dendrimers are a new class of artifical macromolecules with well-defined
      hyperbranched structures which endue these promising materials with a wide
      variety of applications. They are useful tools in drug discovery and allow bio
      active molecules to be presented in a highly multi-valent fashion on the surface.
      Recently, the use of dendrimers as scaffolds of carbohydrates to synthesize
      glycodendrimers with high and specific affinities to various receptors has made
      it possible for these dendritic materials to participate in extracellular and
      intracellular biochemical processes. References on synthesis and biological
      applications of glycodendrimers in the literatures demonstrate that dendrimers
      are suitable candidates as scaffolds of these bioactive carbohydrates. In this
      mini-review, different approaches to construct glycodendrimers as well as their
      promising applications in biological systems are fully discussed.

PMID- 18045088
TI  - Supramolecular systems-based HPLC for chiral separation of beta-adrenergics and
      beta-adrenolytics in drug discovery schemes.
AB  - Increasing amount of data considering polymorphism, splice variants and various
      affinity states of beta-adrenoceptors has resulted in a new range of
      opportunities for enantiopure beta-adrenergic and beta-adrenolytic drug discovery
      and continuous development of reliable high-throughput screening procedures
      enabling tissue specific pharmacological evaluation of these drugs. Design and
      fast pharmacological profiling of single enantiomeric molecules combining beta
      adrenoceptor affinity with other pharmacophores is also still challenging
      ability. As the use of chiral stationary phases in HPLC has particularly
      benefited from results of supramolecular chemistry, this review summarises recent
      achievements provided by this technique in deciphering of enatiorecognition
      phenomena affecting pharmacological selectivity of beta-adrenergics and beta
      adrenolytics and modifying the efficiency of currently proposed beta-adrenoceptor
      targeted therapies. Detailed characteristic of chiral separation performance of
      these drugs in the range of available supramolecular HPLC systems has also been
      presented.

PMID- 18045089
TI  - Thermal properties and microstructures of methylated polyrotaxane solutions.
AB  - Aqueous solutions of polyrotaxanes consisting of poly(ethylene glycol) and
      methylated alpha-cyclodextrins (alpha-CD) were studied by means of differential
      scanning calorimetry (DSC), dynamic light scattering, and X-ray diffraction in
      order to investigate the effect of the degree of methylation on thermoresponsive
      behavior. Polyrotaxanes with a degree of methylation higher than 50% had a lower
      critical solution temperature (LCST) and showed reversible associations and
      dissociations in water. In the transmittance measurements, the cloud point of
      methylated polyrotaxanes (MePR) shifted to a lower temperature with an increase
      in the degree of methylation. The heating curve obtained by DSC for the nearly
      permethylated polyrotaxane showed one broad endothermic peak that was associated
      with the microcrystallization of methylated CDs by hydrophobic interactions. On
      the other hand, the DSC profiles for partially methylated polyrotaxanes had
      several endothermic peaks, indicating multiple phase transitions of the MePR
      solutions. The results imply that the thermal properties of the MePR-water system
      are significantly affected by not only the methyl groups on alpha-CDs but also by
      the remaining hydroxyl groups.

PMID- 18045090
TI  - Cyclodextrin complexes: chiral recognition and complexation behaviour.
AB  - Cyclodextrins are well known in supramolecular chemistry as host molecules
      capable of engulfing molecules in their hydrophobic cavity via noncovalent
      interactions. Although cyclodextrins are frequently used for chiral separation of
      racemates, the mechanism of chiral recognition has not yet been fully
      characterised. The current investigation was aimed at examining chiral
      recognition mechanism in order to construct an in silico method for prediction of
      chiral recognition. Amino acids were selected as model guest, whereas alphaCD was
      used as model host. The results of molecular docking and molecular dynamic
      calculations were compared to results of stability constant determination and
      capillary electrophoresis measurements of enantioseparations. Positive
      correlation between binding strength and chiral separation ability was found.
      However, the small energy differences between interaction energy of each
      enantiomer with alphaCD fell into the range of standard error of molecular
      docking calculations limiting its applicability for in silico prediction.
      Examining the stability of complex geometry during molecular dynamics simulation
      revealed that stable complex geometry is likely to be a prerequisite for chiral
      recognition. This hypothesis was tested on methylderivatized tryptophan. Indeed,
      chiral separation of beta-methyl-tryptophans by alphaCD could be successfully
      predicted by examining the complex geometries during molecular dynamic
      simulation.

PMID- 18045091
TI  - 1H NMR investigations of inclusion complexes between beta-cyclodextrin and 1
      hexadecanol.
AB  - The inclusion complex between beta-CD and 1-hexadecanol is synthesized and
      identified via (1)H NMR spectrum. The possible conformation of the inclusion
      complex is figured out. Via MM2 calculations, the possibility of complexation is
      verified.

PMID- 18045092
TI  - Overview of murine atherosclerosis series.
AB  - This volume recognizes the critical and central role of the mouse in experimental
      atherosclerosis pathology. Atherosclerosis is a complex and chronic inflammation
      in which multiple modulating factors may play a role. Its chronicity and
      complexity make it very difficult to study the detailed mechanisms of
      atherogenesis in unregulated human populations. The search for atherogenic
      mechanisms requires a model in which these mechanisms simulate those inferred in
      humans, and in which controlled experiments may be conducted in a reasonable
      timeframe and at manageable expense. The mouse recommends itself as a small
      animal model with a short life span in which atherosclerosis similar in character
      to human atherosclerosis may be induced under controlled conditions. With the
      development of genetic models of atherosclerosis the mouse has become a very
      accessible model, especially with the very large genetic data base about this
      species in relation to human biology that has become available.

PMID- 18045093
TI  - Diet effects on atherosclerosis in mice.
AB  - The development of atherosclerosis in mice can be dramatically affected by the
      composition of the diet. The nutrients that seem to have the greatest impact on
      the atherosclerotic process in not only mice but also humans are fat and
      cholesterol. For this reason, many murine diets have been created that contain
      different levels of cholesterol and numerous types of fat. Typically, these diets
      cause the accumulation of atherogenic, apoB-containing lipoproteins in plasma and
      depending upon the severity of the hypercholesterolemia stimulate the formation
      of aortic atherosclerosis that often progresses from fatty streak lesions to
      advanced, fibrous plaques. In this review, we compare the abilities of diets
      enriched with various amounts of cholesterol and different types of saturated,
      monounsaturated, and polyunsaturated fats to promote atherosclerosis in an
      assortment of mouse models. In addition, we make recommendations concerning the
      utilization of these diets to promote atherosclerotic lesion formation in mice.

PMID- 18045094
TI  - Genetics of atherosclerosis in murine models.
AB  - The pathology of atherosclerotic lesions that develop in mouse models of
      atherosclerosis, such as those lacking apolipoprotein E or lacking the low
      density lipoprotein receptor, is very similar to that seen in human patients.
      Consequently, genetic approaches to studying atherosclerosis in these mouse
      models have produced a wealth of information relevant to the genetic factors and
      pathways that modify the early stages of atherosclerosis in humans. Despite these
      advances, the later stages of atherosclerosis in humans, including spontaneous
      plaque rupture and hemorrhage, have not been observed reliably in current mouse
      models. Increasing sophistication and use of genetic manipulations, however, has
      produced significant advances in modeling these processes. The use of genetic
      tools to examine the physiology, pathology, and cell biology of atherosclerosis
      will enhance elucidation of the pathogenesis of the disease and lead to the
      development of novel therapeutic strategies.

PMID- 18045095
TI  - Gender as a regulator of atherosclerosis in murine models.
AB  - The risk of development and progression of atherosclerosis is different between
      males and females. Premenopausal women have a lower risk of developing
      atherosclerosis and cardiovascular disease than men. However, after the onset of
      menopause the protection associated with gender is lost and the risk of women
      developing atherosclerosis gradually approaches that of men. In an effort to
      treat the elevated risk of cardiovascular disease in postmenopausal women,
      hormone replacement therapy has been used. However, the results of the randomized
      trials of the Women's Health Initiative indicated that hormone replacement
      therapy may not be cardioprotective. The use of mouse models have aided in the
      understanding of atherosclerosis for many years. These models along with the
      gender effects attributed to sex hormones are being used to generate a more
      complete understanding of the development of atherosclerosis. Mice lacking one or
      both of the genes for estrogen receptors have highlighted the role of estrogen in
      atherosclerosis. In addition to estrogen, the effects of testosterone have been
      researched in many animal models and several mechanisms incorporating its role in
      cholesterol homeostasis have emerged. Our understanding of the pathways involved
      in gender effects on cardiovascular disease is incomplete, however, a plethora of
      animal models offer the opportunity to dissect the molecular mechanisms involved.

PMID- 18045096
TI  - Atherosclerosis and arterial blood pressure in mice.
AB  - Increased blood pressure is a consistent risk factor for the development of
      atherosclerotic diseases in humans, although the basis for this relationship is
      unknown. Genetically engineered mice are now commonly used to study mechanisms of
      atherosclerosis. More recently, blood pressure can be reliably measured in
      conscious mice using either tail cuff or telemetric techniques. Thus, mouse
      models permit the investigation of the complex interactions of blood pressure and
      atherogenesis. Most mouse models exhibiting hypertension have increased
      atherosclerotic lesion size, although there have been exceptions to these
      findings. Also, there are several reports that have used methods to decrease
      blood pressure and demonstrated reduced atherosclerosis. In contrast, there are
      many studies in which atherosclerosis has been altered without changes in blood
      pressure, and conversely, studies in which blood pressure changes did not alter
      atherosclerosis. Studies that have specifically defined the role of elevated
      systolic blood pressure on the development of atherosclerosis have uniformly
      demonstrated that pressure per se is not responsible for changes in lesion
      development. Thus, while increased systolic blood pressure is frequently
      associated with atherosclerosis, the stimulus for the hypertension appears to be
      the major determinant of atherogenesis rather than pressure per se. A consistent
      theme in the literature has been that perturbations of the renin angiotensin
      system display the strongest correlations between blood pressure and
      atherosclerosis.

PMID- 18045097
TI  - Adipose tissue and the vessel wall.
AB  - The prevalence of obesity is rising dramatically in developed and developing
      countries. Obesity contributes to increased mortality from numerous causes, but
      the most important of these is cardiovascular death. The relationship between
      obesity and atherogenesis is multifactorial, including alterations in the
      composition and level of lipoproteins, changes in blood pressure, and changes in
      circulating coagulation and inflammatory factors. Mouse models can be useful for
      dissecting selected aspects of this complex relationship. One area in which these
      models can be of particular value is in investigating the effect of secretory
      products of adipose tissue on the vessel wall. Adipocytes and adipose tissue
      secrete numerous factors and their level of expression is altered in obese
      states. Adipose tissue and adipocytes produce adiponectin, resistin, leptin, and
      apolipoproteins (serum amyloid A and apoE); all of which can directly impact
      vessel wall homeostasis. Mouse models utilizing deletion or overexpression of
      many of these factors have demonstrated an important impact of these on vessel
      wall homeostasis. Subsequent to the development of obesity, factors secreted from
      adipose tissue have also been shown to have direct effect on liver production of
      systemic inflammatory factors. Mouse models have validated the importance of
      angiotensin II, TNFalpha, and MCP-1 for impacting vessel wall health in obese
      states. In summary, excess adipose tissue produces myriad changes in organismal
      homeostasis with potential impact on the vessel wall. The power of mouse genetics
      permits targeted mechanistic investigation for understanding how obesity
      accelerates atherosclerosis in a complex in vivo milieu.

PMID- 18045098
TI  - Effects of diabetes on murine lipoproteins and vascular disease.
AB  - The creation of mouse models that recapitulate human diabetic cardiovascular
      disease remains a significant challenge. Part of the problem relates to the lack
      of a clear understanding of the human phenotype. Although improved insulin-treat
      of hyperglycemia reduces cardiovascular events in patients with type 1 diabetes,
      similar data are not available in type 2 diabetes. Moreover, whether human
      vascular disease is increased by hyperglycemia, defective insulin actions, or
      other factors is not known. Significant progress has been made in developing
      models of both type 1 and type 2 diabetes in mouse that can be used to study the
      relationship between hyperglycemia and atherosclerosis. This review describes
      mouse models that recapitulate specific aspects of diabetic dyslipidemia,
      hyperglycemia/insulin resistance, and diabetic vascular disease. Overall, the
      studies have clearly demonstrated that hyperlipidemia is a major driver of
      atherosclerotic vascular disease in the mouse. The effects of hyperglycemia and
      insulin resistance on murine atherosclerosis remain uncertain.

PMID- 18045099
TI  - The influence of acute phase proteins on murine atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory reaction that is initiated in response
      to hyperlipidemia and the retention and modification of lipids within the
      vascular wall. Chronic inflammatory states lead to steady low-level induction of
      the acute phase reaction and chronic inflammation is associated with elevated
      cardiovascular disease and atherosclerosis. The acute phase reaction is mediated
      by cytokines and results in significant changes in the plasma level of several
      proteins referred to as acute phase proteins. The liver is a major source of
      these proteins. Several recent studies in humans have shown that levels of acute
      phase proteins are modified in patients with established cardiovascular disease
      or are predictors of future disease. Whether these acute phase proteins are a
      biomarker of inflammation or have a direct role in the development of
      atherosclerosis is not clear. Murine models of atherosclerosis have been used to
      address the role of acute phase proteins in atherosclerosis. Modification of the
      expression level of these proteins has shown that the individual acute phase
      proteins are either pro-atherogenic or anti-atherogenic. The absence of an
      overall trend is perhaps not surprising given the complex nature of the acute
      phase response.

PMID- 18045100
TI  - Metabolic syndrome as a modifier of atherosclerosis in murine models.
AB  - The Metabolic Syndrome is a common metabolic disease associated with an increased
      risk for atherosclerotic cardiovascular disease and mortality. In contrast to
      "traditional" risk factors for atherosclerosis, such as low-density lipoprotein
      cholesterol, the Metabolic Syndrome represents a network of interacting risk
      factors stemming from the metabolic complexity of this disease. For this reason,
      dissection of the cellular and molecular pathways underlying atherosclerosis
      susceptibility in the Metabolic Syndrome has been difficult. To facilitate this
      endeavor, several murine models have been recently developed. Despite their
      imperfect representation of the Metabolic Syndrome and atherosclerosis in humans,
      these models have provided important mechanistic insights and revealed novel
      molecular pathways. Furthermore, murine models are invaluable for the evaluation
      of therapeutic approaches and will no doubt facilitate the genetic dissection of
      atherosclerosis-susceptibility in the Metabolic Syndrome.

PMID- 18045101
TI  - Gene therapy for the induction of chimerism and transplant tolerance.
AB  - Technical advances in transplant surgery and the development of powerful and
      effective immunosuppressive drugs have contributed to the success of organ
      transplantation as a medical treatment for patients with end-stage diseases.
      Associated with this procedure, however, is a dependence on life-long
      immunosuppressive drugs, which are required to prevent graft rejection. These
      agents render the patient susceptible to infections, tumors and various side
      affects. The ability to achieve tolerance to organ grafts would free transplant
      patients from lifelong dependency on pharmacological agents with harmful side
      effects. Several laboratories have shown that tolerance can be achieved by the
      induction of mixed cell chimerism and/or by molecular chimerism achieved by gene
      transfer techniques prior to graft placement. Molecular chimerism, induced by
      transplantation of autologous bone marrow expressing either allo- or xenoantigens
      has the potential to induce tolerance without the development of graft vs. host
      disease. The application of gene transfer techniques to induce chimerism has been
      shown to reshape the immune repertoire by mechanisms that include clonal
      deletion, the induction of central tolerance or generation of regulatory T cells
      that would eliminate the need for immunosuppressive drugs. Optimization of this
      methodology for clinical use could therefore revolutionize the field of
      transplantation. This review summarizes the recent studies which have compared
      the efficacy of different vectors, conditioning regimens, and transduction
      conditions leading to new and improved techniques for the application of gene
      therapy to induce chimerism and transplant tolerance to both allografts and
      xenografts.

PMID- 18045102
TI  - Gene therapy in cerebrovascular diseases.
AB  - Several studies utilize gene therapy technology to study the molecular mechanisms
      and therapeutic approaches to a variety of neurological diseases. Although gene
      therapy for neuro-oncology and neurodegenerative diseases has advanced to the
      clinical arena, those of cerebrovascular nature have remained in the experimental
      stage and demonstrate promising results. Before gene therapy in cerebrovascular
      disorders can be successful, various obstacles need to be addressed. In this
      review, we focus on the fundamentals of gene therapy adapted to cerebrovascular
      diseases, which include cerebral ischemia, post-subarachnoid hemorrhagic
      vasospasm, arteriovenous malformations, etc. We discuss: 1) the utilization of
      gene delivery vehicle, through viral, non-viral, or cellular vectors; 2) the
      routes and specific delivery of the vector to its target cells or tissue in the
      central nervous system; 3) the studies that have utilized in vivo and ex vivo
      gene delivery approaches and their success in the attenuation of cerebrovascular
      injuries; and finally 4) the future of gene therapy in this field.

PMID- 18045103
TI  - Neuroprotective gene therapy for the treatment of inherited retinal degeneration.
AB  - Inherited retinal degeneration (IRD) affects around 1/3000 of the population in
      Europe and the United States. It is a diverse group of conditions that results
      from mutations in any one of over 100 different genes. Many of the genes have now
      been identified and their functions elucidated, providing a major impetus to
      develop gene-based treatments. Whilst gene replacement and gene silencing
      strategies offer prospects for the treatment of specific inherited retinal
      disorders, other disorders may be less amenable to these corrective approaches.
      These conditions include, in particular, those associated with abnormal retinal
      development and those in which retinal degeneration is advanced at birth.
      Furthermore, the development of individualized corrective gene therapy strategies
      for patients with disorders due to very rare mutations may be unfeasible.
      However, generic gene therapy strategies that aim not to correct the gene defect
      but to ameliorate its consequences offer the possibility of therapies that are
      widely applicable across a range of conditions. One potential strategy in these
      cases is to halt or delay the process of cell death, so that useful visual
      function can be maintained throughout the lifetime of an affected individual. It
      has been shown in variety of experimental models over the last three decades,
      that neurotrophic factors have the potential to delay neuronal apoptosis.
      Neurotrophic factors are small proteins which have relatively short half lives
      and a requirement for repeated administration has limited their clinical
      application. Since these proteins do not ordinarily cross the blood-brain
      barrier, previous approaches have relied upon intrathecal infusion pumps or
      similar complex devices to sustain elevated neurotrophin levels within the
      central nervous system (CNS). However, sustained delivery through viral vector
      mediated expression of genes encoding neurotrophic factors may circumvent the
      potential side effects of repeated administration. In this review we shall
      explore some of the concepts of neurotrophic gene therapy and how this might be
      applicable to preserving vision in inherited retinal degenerations.

PMID- 18045104
TI  - Clinical applications of gene therapy in head and neck cancer.
AB  - Despite advances in surgery, radiotherapy, and the incorporation of novel
      systemic agents into treatment, long-term outcomes of patients with head and neck
      cancer remain unsatisfactory. The growing understanding of head and neck cancer
      biology suggests that targeting molecular events governing carcinogenesis or
      tumor progression may provide novel therapeutic approaches for head and neck
      cancer. Squamous cell carcinoma of the head and neck (SCCHN) is characterized by
      locoregional spread and is clinically accessible, making it an attractive target
      for intratumoral gene therapy, a potentially efficacious experimental treatment.
      Systemic delivery of gene therapy may be also possible, albeit with several
      limitations. In this review we will discuss the rationale, delivery methods, and
      accumulated clinical data with cancer gene therapy in SCCHN.

PMID- 18045105
TI  - Gene therapy in the transplantation of allogeneic organs and stem cells.
AB  - Most of the current hematopoietic stem cell (HSC) -directed gene therapy
      applications have focused on the replacement of defective or deficient genes in
      an autologous setting. More recently HSC gene therapy applications have also
      included the enhancement or improvement of HSC features. Allogeneic HSCs have
      been used to facilitate and improve allogeneic transplantation and to achieve
      tolerance to transplanted cells, tissues or organs. Different gene transfer
      approaches addressing a variety of immunomodulatory mediators contributing to
      graft tolerance or immunological ignorance may have a critical role in improving
      long-term graft survival. Allogeneic tissues are frequently recognized by
      allospecific T cells as foreign and are rapidly rejected in the absence of
      immunosuppression. The higher susceptibility to cancer and infectious diseases of
      immunosuppressed patients led to investigation of new therapies to induce graft
      specific tolerance. Peripheral tolerance to allogeneic grafts can be achieved by
      a variety of mechanisms including clonal deletion, suppression caused by
      regulatory T cells and anergy induction associated with microchimerism effect. In
      the last decades, potential candidates to confer allograft protection were
      identified. In this review, we summarize ongoing strategies and developments in
      genetic manipulation of cells, tissues and organs for allogeneic transplantation
      including modulating the effector arm of the immune response.

PMID- 18045106
TI  - Lung cancer vaccines.
AB  - Cytotoxic chemotherapy is associated with modest survival advantage as initial
      treatment of advanced lung cancer. However, toxicity and minimal benefit to use
      second line treatment justifies exploration of alternative approaches. Recent
      understanding of mechanisms by which tumor antigen recognition can be enhanced
      has justified development of a recent flurry of vaccine trials in lung cancer.
      Preliminary results suggest a remarkably high safety profile and significant
      activity with respect to improvement in time to progression and survival in
      comparison to historical controls or lower dose treated cohorts, particularly in
      non small cell lung cancer. This review summarizes current results of vaccine
      trial development in non small cell and small cell lung cancer.

PMID- 18045107
TI  - Antibody neutralization.

PMID- 18045108
TI  - Prospects of HIV Env modification as an approach to HIV vaccine design.
AB  - So far, all efforts to engineer immunogens that would elicit broadly reactive
      anti-HIV neutralizing antibody responses have not been successful. In the past
      few years, however, key information on the structure of the epitopes recognized
      by several broadly reactive anti-HIV neutralizing antibodies (NAbs), the
      structures of these NAbs themselves and the molecular interaction between these
      NAbs and their epitopes has emerged, that promises to guide the design of better
      immunogens. In order to enhance the immunogenicity of conserved neutralization
      epitopes on Env, certain modifications such as variable loop-deletion,
      elimination of glycosylation sites, or epitope-repositioning, are being
      investigated. So far, however, all available data from immunization studies
      indicate that the effect such structural modifications have on Env immunogenicity
      is unpredictable. This implies that despite the significant progress made in
      elucidating the interaction of NAbs with their targets at the molecular level, a
      significant iterative effort is required to identify immunogens that would elicit
      the much anticipated broad anti-HIV neutralizing antibody responses.

PMID- 18045109
TI  - Designing immunogens to elicit broadly neutralizing antibodies to the HIV-1
      envelope glycoprotein.
AB  - To date HIV-1 vaccines have not been able to elicit potent, long lasting, and
      broadly neutralizing antibodies to the virus. Our knowledge of HIV envelope
      glycoprotein (Env) structure/function and the existence of a handful of broadly
      neutralizing antibodies is guiding rational immunogen design. We review here the
      potential targets on the HIV Env (the glycan shield, the CD4 binding site, the
      coreceptor binding site, Env fusion intermediates, and the membrane proximal
      region) and their associated rational immunogen design strategies. Moreover, we
      discuss immune dampening and immune refocusing strategies designed to counter
      immunodominant, decoy responses generated by the virus. In this regard, an
      immunogen design strategy of "in vitro de-evolution" is presented, which begins
      to distill the HIV Env to its most critical, core functional domains. While we
      are beginning to have some understanding as to where we would like out immune
      system to go, we find that our immune repertoire may actually have limits that
      preclude successful completion of the task at hand. The repertoire limits appear
      to be a byproduct of autoantibody tolerance mechanisms and the complex structural
      requirements for effective, potent broadly neutralizing antibodies. Nevertheless,
      the hope is that through novel insights and creative solutions that we will be
      able to design immunogens capable of eliciting broadly neutralizing antibodies to
      the HIV envelope glycoprotein.

PMID- 18045111
TI  - Clade specific neutralising vaccines for HIV: an appropriate target?
AB  - The enormous diversity of the human immunodeficiency virus (HIV) has led to the
      idea that designing vaccines to specific geographic regions, or clades, could
      simplify the complexity of the task. Yet, despite the sequence diversity, all HIV
      viruses known to date interact with the same cellular receptors (CD4 and/or a
      coreceptor, CCR5 or CXCR4). In this review we examine the existing evidence to
      support a clade-specific vaccine strategy for induction of neutralising
      antibodies. We concentrate on lessons learnt from natural infection of humans. In
      short, the vast majority of studies to date indicate that neutralisation of HIV-1
      is not clade specific. Potent sera tend to neutralise a range of heterologous
      viruses with no apparent clade preference, and none of the human neutralising
      monoclonal antibodies so far generated demonstrate significant clade preference.
      All but one of the most broadly neutralising antibodies are to functional regions
      involved in receptor interactions and plasma membrane fusion. Given these facts,
      we suggest that vaccine approaches that focus on 'clade-specific' and 'clade
      generic' vaccines will logically converge on the same functionally conserved
      envelope structures. It still remains to be determined whether or not the task of
      designing a 'clade-generic' vaccine could be simplified by focusing on the viral
      envelopes with 'transmitting phenotypes'.

PMID- 18045110
TI  - Roles of HIV-1 Env variable regions in viral neutralization and vaccine
      development.
AB  - A major focus of HIV-1 vaccine development has been directed towards a limited
      number of broadly conserved epitopes in the Envelope (Env) proteins that are
      sensitive neutralization targets in many primary isolates. However, evidence
      suggests that these epitopes are poorly immunogenic; similar antibodies are
      rarely produced by infected subjects, nor are they induced by various immunogens
      designed to express these epitopes. On the other hand, the major variable domains
      of Env are highly immunogenic; antibodies against these regions are common in
      sera of infected patients and easily generated upon immunization. Although these
      epitopes are extremely sensitive neutralization targets in some laboratory
      strains and primary isolates, the neutralization range of antibodies against
      these sites is limited. This review describes potent neutralization epitopes
      located in the variable regions of Env and discusses the bases for the limited
      neutralization breadth of antibodies against these targets. Strategies are
      discussed for using available information to design immunogens capable of
      exploiting the potential of these regions as vaccine targets.

PMID- 18045112
TI  - CD4-induced epitopes in the HIV envelope glycoprotein, gp120.
AB  - The HIV surface glycoprotein, gp120, contains conserved and functional domains
      that exist within a viral envelope spike that is otherwise highly variable with
      respect to conformation, sequence and structure. Termed CD4-induced epitopes,
      these domains are stabilized on transition state gp120 structures as a
      consequence of CD4 receptor engagement. These nuggets of conservation naturally
      attract the attention of those seeking to develop vaccine and therapeutic
      strategies to fight infection by diverse HIV strains. However, an appreciation
      for the immunological relevance and practical value of CD4-induced epitopes is
      still evolving. This review covers the current findings related to the
      accessibility, antigenicity and immunogenicity of CD4-induced epitopes on gp120.

PMID- 18045113
TI  - Centralized HIV-1 envelope immunogens and neutralizing antibodies.
AB  - Centralized HIV-1 genes (consensus, most recent common ancestor and center of the
      tree) have recently been explored for induction of broadly reactive immune
      responses to overcome the extraordinary genetic diversity among HIV-1 strains.
      Although all of these strategies are based on artificial sequences predicted by
      computer programs, they retain biological function, and use the CCR5 co-receptor
      for entry into target cells as transmitted HIV-1 Envs. Results from laboratory
      animals indicate that centralized immunogens are superior to many wild-type
      immunogens for inducing cross-subtype T and B cell immune responses. Structural
      modifications have improved the ability of consensus Envs to elicit antibody
      responses that neutralize a spectrum of HIV-1 Env pseudoviruses. However, the
      more difficult to neutralize tier 2 Env pseudoviruses are generally not
      neutralized well by anti-consensus Env antibodies, indicating the need for
      further modifications, new formulations, or additional strategies to generate
      antibodies that neutralize a full spectrum of transmitted HIV-1 strains.

PMID- 18045114
TI  - Transmission of HIV-1 in the face of neutralizing antibodies.
AB  - In most cases of HIV-1 transmission, only a subset of variants is transmitted
      from the index case to the newly infected individual. Understanding the
      characteristics of these transmitted variants may aid in developing new methods
      to halt the spread of HIV-1. Studies evaluating the genotypic and antigenic
      properties of transmitted variants have provided insights into how the selective
      pressures applied during different modes of transmission uniquely imprint the
      infecting viruses. In the setting of sexual transmission, variants with increased
      neutralization sensitivity appeared to be selected during transmission in
      discordant subtype C-infected couples, although transmitted variants from
      different risk groups and HIV-1 subtypes did not demonstrate increased
      neutralization sensitivity, suggesting this may not be a consistent feature of
      transmitted variants. Studies of both mother to child transmission (MTCT) and
      superinfection, where preexisting NAbs are present at the time of exposure,
      provide opportunities to analyze whether the breadth and potency of the NAb
      response influence the incidence of new infections. MTCT resulted in selection
      for variants that were resistant to maternal antibodies, suggesting that maternal
      antibodies can protect the baby from those variants that are susceptible to the
      antibodies present. There are some data to suggest that poor neutralizing
      antibody (NAb) responses are present in cases of superinfection, although these
      data are preliminary. Defining the characteristics of the viruses transmitted in
      the presence and absence of NAbs as well as defining the NAb responses that fail
      to protect from infection during MTCT and superinfection may provide critical
      insights into the antibody responses that are needed for effective vaccines and
      other prophylactic therapeutics.

PMID- 18045115
TI  - Neutralizing antibodies in mucosal secretions: IgG or IgA?
AB  - The mucosal immune response to HIV weighs in heavily on the battle against it, as
      the majority of infections occur via the mucosal route. The antibody response in
      the mucosae, specifically the genital tract, is characterized by binding and, in
      some studies, neutralizing HIV-specific IgG and IgA antibodies. Ample evidence,
      however, points to discrepancies and difficulties in the detection of HIV
      specific IgA in HIV-positive subjects, and an even more pronounced divide
      surfaces in studies done with individuals exposed to HIV, but uninfected. Reports
      in the literature detail HIV-specific (in some cases, neutralizing) IgA
      antibodies, in the absence of specific IgG, in the serum and mucosal secretions
      of virus-exposed, seronegative subjects; this has given rise to speculation that
      HIV-specific IgA provides a protective immune response to the virus in high-risk
      individuals who remain seronegative. Contradictory results, however, describe the
      absence of both IgA and IgG HIV antibodies in the mucosal secretions of similar
      cohorts. Considering the importance of the antibody response to ascertaining the
      correlates of HIV immunity, as well as on vaccine research and development, this
      review addresses the relevant studies and their implications.

PMID- 18045116
TI  - Antibody-mediated neutralization and simian immunodeficiency virus models of
      HIV/AIDS.
AB  - Over the last two decades, use of SIV for experimental infection of Asian
      macaques has provided important leads in the quest for an AIDS vaccine, served as
      the genesis of recombinant SIV/HIV viruses (SHIV), and perhaps most importantly,
      helped establish or confirm biological relevance for a variety of hypotheses
      related to the host immune response to infection and the corresponding viral
      strategies for evading that response. The env genes of HIV-1 and SIV encode
      proteins bearing a high degree of structural similarity and sharing an identical
      suite of essential functions. The Env complexes formed by these proteins are
      present on the surface of virus-producing cells and virions, where they are the
      primary targets of the host neutralizing antibody response. In this review, we
      briefly describe the similarities between HIV-1 infection and SIV experimental
      models, then focus specifically on the use of the SIV/macaque model as a tool for
      understanding the humoral immune response to infection and resistance to antibody
      mediated neutralization in HIV infection and AIDS.

PMID- 18045117
TI  - HIV-1 neutralization: mechanisms and relevance to vaccine design.
AB  - Antibody (Ab) mediated neutralization is a crucial means of host resistance to
      many pathogens and will most likely be required in the development of a vaccine
      to protect against HIV-1. Here we examine mechanistic aspects of HIV-1
      neutralization with attention to recent studies on the stoichiometric, kinetic
      and thermodynamic parameters involved. Neutralization of HIV-1, as with any
      microbe, minimally requires an initial molecular encounter with Ab. Ab occupancy
      of functional heterotrimers of the envelope glycoproteins, gp120 and gp41 (Env),
      indeed appears to be the dominant mechanism of neutralization for HIV-1. However,
      the Ab-binding site, the parameters mentioned above, as well as the stages and
      duration of vulnerability to Ab recognition, prior to and leading up to viral
      entry, each have a distinct impact on the mechanism of neutralization for any
      given Ab specificity. With HIV-1, the problems of mutational variation and
      neutralization resistance, coupled with the lability and conformational
      heterogeneity in Env, have stimulated the search for rational approaches to Env
      immunogen design that are unprecedented in vaccinology.

PMID- 18045118
TI  - Broadening our view of protective antibody responses against HIV.
AB  - Upon viral exposure, antibodies serve as a first line of defense and can act by
      preventing infection or reducing the viral burden. The ability of antibodies to
      confer protection against HIV has been demonstrated by several studies using the
      passive transfer of neutralizing antibodies in the non-human primate challenge
      model. Therefore, efforts have been made to induce a similarly protective humoral
      immune response by vaccination with antigens derived from HIV. Thus far, the
      results have been disappointing. Humoral immune responses elicited via
      vaccination display activities that are generally much less potent and broad as
      compared to those induced during natural infection. However, recently there have
      been increased efforts to systematically identify and compare the epitopes
      potentially critical to the generation of protective antibody responses in the
      hope that this will lead to improved strategies and superior immunogen design. As
      a critical part of this process, novel methods to monitor protective antibody
      responses will also need to be vigorously explored and improved, then validated
      in both preclinical and clinical settings.

PMID- 18045119
TI  - Passive immunization as tool to identify protective HIV-1 Env epitopes.
AB  - The HIV-1/AIDS epidemic continues to escalate, and a protective vaccine remains
      elusive. The first vaccine candidate, gp120, did not induce broadly neutralizing
      antibodies (nAbs) against primary HIV-1 isolates and was ineffective in phase III
      clinical trials. Attention then focused on generating cytotoxic lymphocyte (CTL)
      based vaccines. Interest in anti-HIV-1 nAbs was renewed when passive immunization
      with human neutralizing monoclonal antibodies (nmAbs) completely protected
      macaques after intravenous and mucosal challenges with simian-human
      immunodeficiency viruses (SHIVs) encoding HIV-1 env. These nmAbs targeted
      conserved, functionally important epitopes on gp120 and gp41. Protection in
      primate/SHIV models was observed when nmAbs were used singly (nmAbs 2G12, b12)
      and in various combination regimens (nmAbs b12, F105, 2G12, 2F5, 4E10). Passive
      immunization, a well-established tool to determine the correlates of protective
      immunity, thus identified protective epitopes. The three-dimensional structures
      of some of the latter were recently elucidated, generating important information
      to design nAb-response-base immunogens. However, several of the protective nmAbs
      were found to exhibit autoreactivity, raising the possibility that B-cell
      responses against the cognate epitopes may be difficult to induce by active
      immunization. It will be important to explore whether broad neutralization can be
      dissociated from autoreactivity. Future experiments will reveal whether other
      conserved HIV-1 Env epitopes exist, antibodies against which will be broadly
      neutralizing in vitro, protective as passive immunization in SHIV-challenged
      macaques, but lacking autoreactivity. Since all protective epitopes identified to
      date are located on HIV-1 clade B Env, future studies should include analysis of
      nmAbs against non-clade B strains.

PMID- 18045120
TI  - Inhibitors of HIV-1 protease: current state of the art 10 years after their
      introduction. From antiretroviral drugs to antifungal, antibacterial and
      antitumor agents based on aspartic protease inhibitors.
AB  - The introduction of highly active antiretroviral therapy (HAART) in 1996
      dramatically changed the course of HIV infection. This therapy involves the use
      of at least three agents from two distinct classes of antivirals: a protease
      inhibitor (PI) in combination with two nucleoside/nucleotide reverse
      transcriptase inhibitors (N(t)RTIs), or a non-nucleoside reverse transcriptase
      inhibitor (NNRTI) in combination with NRTIs. Nine drugs containing PIs are
      clinically available: the first generation ones, saquinavir, ritonavir,
      indinavir, nelfinavir, and amprenavir, and the second generation ones,
      fosamprenavir (the amprenavir prodrug), lopinavir, atazanavir, and tipranavir.
      Many other compounds are in advanced clinical evaluation, such as among others
      TMC-114, whereas a lot of different other effective HIV protease inhibitors were
      reported, mainly by using amprenavir and TMC-114 as lead molecules. The main
      goals of research in this field are: (i) the design of better pharmacological
      agents, devoid of severe side effects, resistance problems and with simple
      administration schedules (preferably once daily), and (ii) achieving eradication
      of the virus, and possibly, a definitive cure of the disease. A review on the
      pharmacology and interactions of these agents with other drugs is presented here,
      with emphasis on how these pharmacological interferences may improve the clinical
      use of antivirals, or how side effects due to PI drugs may be managed better by
      taking them into account (such as for example ritonavir boosting of other PIs
      which reduces dosages and administration schedules of these drugs). Except for
      being highly effective in the treatment of HIV infection, recent reports showed
      this class of drugs to be effective as antitumor agents, as antibacterials (for
      example against Mycobacterium tuberculosis infection), antifungals (against
      Candida albicans), antimalarials, antiSARS and anti-influenza agents.

PMID- 18045121
TI  - Renin-angiotensin system inhibitors as therapeutic alternatives in the treatment
      of chronic liver diseases.
AB  - The renin-angiotensin system (RAS) is frequently activated in the patients with
      chronic liver diseases, and recent studies have shown that RAS plays a pivotal
      role in the progression of chronic liver diseases, i.e., liver fibrosis and
      hepatocellular carcinoma (HCC). Angiotensin-II (AT-II) reportedly stimulates
      contractility and proliferation of the activated hepatic stellate cells, and
      increases the transforming growth factor-beta (TGF-betabeta expression through
      angiotensin type-I receptors (AT1-R). Many studies have demonstrated that the
      clinically used angiotensin-converting enzyme inhibitors (ACE-I) and AT1-R
      blockers (ARB) significantly attenuated the liver fibrosis development in the
      experimental studies and clinical practice. AT-II also strongly promotes
      neovascularization, which plays a pivotal role in tumor development. AT-II
      induces a potent angiogenic factor; namely, the vascular endothelial growth
      factor (VEGF). It has been reported that ACE-I significantly attenuated the
      experimental HCC growth and hepatocarcinogenesis along with suppression of
      neovascularization. The VEGF expression in the tumor was suppressed by ACE-I,
      too. The combined treatment of ACE-I with other clinically used agents, such as
      interferon, imatinib mesylate, and vitamin K, shows more potent inhibitory
      effects on the development of liver fibrosis and HCC. Since RAS inhibitors are
      widely used in the clinical practice without serious side effects, they may
      represent a potential new therapeutic strategy against the progression of chronic
      liver diseases.

PMID- 18045122
TI  - An updated unified pharmacophore model of the benzodiazepine binding site on
      gamma-aminobutyric acid(a) receptors: correlation with comparative models.
AB  - A successful unified pharmacophore/receptor model which has guided the synthesis
      of subtype selective compounds is reviewed in light of recent developments both
      in ligand synthesis and structural studies of the binding site itself. The
      evaluation of experimental data in combination with a comparative model of the
      alpha1beta2gamma2 GABA(A) receptor leads to an orientation of the pharmacophore
      model within the Bz BS. Results not only are important for the rational design of
      selective ligands, but also for the identification and evaluation of possible
      roles which specific residues may have within the benzodiazepine binding pocket.

PMID- 18045123
TI  - Therapeutic targets in respiratory viral infections.
AB  - Respiratory viral infections account for a substantial proportion of morbidity
      world wide and contribute notably to the socio-economic burden of diseases.
      Amongst the most important viruses identified so far are Rhinoviruses, Influenza
      A and Respiratory Syncytial Virus. The knowledge base has broadened at the
      clinical and experimental level in recent years. However, therapeutic options are
      still limited. This may be partly due to the multiplicity of infectious
      mechanisms and the complex underlying host/virus interactions. The aim of this
      article is to give an overview of the different respiratory viruses involved,
      their major principles of infection and the associated therapeutic targets and to
      review up-to-date virus-specific clinical trials.

PMID- 18045124
TI  - Interactions between growth hormone and the thyroid gland -- with special
      reference to biochemical diagnosis.
AB  - The diagnosis of pituitary disorders is difficult because several hormone systems
      are involved. The clinical presentation is often vague and slowly progressing,
      and clinicians therefore have to rely very much on correct biochemical
      measurements. This is also associated with difficulties since the pituitary
      hormones interact, the binding proteins are influenced by the other axes and a
      variety of other effects, and finally the hormone measurements in serum are not
      totally adequate Several studies have investigated the interaction between the
      thyroid and growth hormone axes with very variable results. The present review is
      focussing on the aspects related to clinical decision making based on biochemical
      assessments. Because of the strong and sometimes unpredictable interrelations
      between the hypothalamo-pituitary thyroid and the hypothalamo-GH-IGF axes, and
      the many pitfalls in the measurement of peripheral hormones and interpretation of
      stimulation tests, clinicians and clinical biochemists should collaborate
      closely. Only then can the diagnostic accuracy and the management of patients
      with both growth hormone and thyroid disorders be improved.

PMID- 18045125
TI  - Computer simulation of antimicrobial peptides.
AB  - Naturally occurring and synthetic peptides may be a novel class of clinically
      useful antibiotics. A large body of experimental data on structure function
      relationships for such peptides is available, but the molecular mechanism of
      their action remains elusive in most cases. Computer simulations can give
      detailed insights into the interactions between peptides and lipid bilayers, at
      least one crucial step in the antimicrobial mechanism. Here we review recent
      simulations of antimicrobial peptides and discuss potential future contributions
      of computer simulations in understanding and ultimately designing antimicrobial
      peptides.

PMID- 18045126
TI  - Valproate and neuroendocrine changes in relation to women treated for epilepsy
      and bipolar disorder: a review.
AB  - Valproic acid (2-n-propylpentanoic acid, VPA) is well-established as a mood
      stabilizer for bipolar disorder, in addition to its application as a treatment in
      neurological disorders such as epilepsy, migraine headaches, and chronic
      neuropathic pain. Its mechanisms of actions in any of the disorders have not yet
      been fully elucidated but currently include GABA-ergic inhibitory effects, the
      suppression of NMDA-mediated excitatory neurotransmission, and possibly effects
      on monoamines and cerebral glucose metabolism. Given the rising use of VPA by
      women of reproductive age for various conditions it is increasingly important to
      understand how VPA affects reproductive and metabolic function in women, yet a
      number of key issues regarding VPA use in women of reproductive age remain
      unclear. These include the question of whether VPA use is associated with the
      development of polycystic ovary syndrome (PCOS)-like features (such as elevated
      androgen concentrations and/or chronic anovulation). The metabolic effects of VPA
      use, particularly on insulin sensitivity and weight gain, are also important to
      understand. Lastly, questions of VPA use during pregnancy and lactation require
      continued attention. This article reviews the current understanding of VPA's
      mechanisms of action, effects on the reproductive and metabolic system, and
      teratogenic qualities, highlighting important future areas of study.

PMID- 18045127
TI  - Application of the O-N intramolecular acyl migration reaction in medicinal
      chemistry.
AB  - The O-N intramolecular acyl migration, also named as an acyl shift or acyl
      transfer reaction, is well-known in organic and peptide chemistry as a simple
      rearrangement which proceeds under very mild aqueous conditions. Despite a long
      history with this reaction, its application in medicinal chemistry has only
      lately been proposed. In the last decade, this reaction has been intensively
      studied and several applications of this rearrangement in medicinal chemistry
      have appeared. O-N Intramolecular acyl migration has been employed in "no
      auxiliary, no byproduct" prodrug strategies (prodrugs of paclitaxel and other
      taxoids, prodrugs of HIV protease inhibitors), for the synthesis of peptides
      containing difficult sequences via "O-acyl isopeptide method", including
      Alzheimer's disease related amyloid beta peptide (Abeta) 1-42, and in the design
      of pH-, photo- or enzyme-triggered click peptides, as a potential powerful tool
      for identifying the pathological functions of amyloid beta peptides in
      Alzheimer's disease. This review summarized recent advances in the application of
      O-N intramolecular acyl migration with special focus on medicinal chemistry.

PMID- 18045128
TI  - Isoflavones, equol and cardiovascular disease: pharmacological and therapeutic
      insights.
AB  - Isoflavones are an important class of phytoestrogens that are found at extrememly
      high levels in soy. Up until recently, daidzein and genistein were considered to
      be the most important and hence most studied isoflavones, however more recently
      attention has shifted to isoflavone metabolies. Equol represents the main active
      product of daidzein metabolism, produced via specific microflora in the gut. It
      has a longer half life and greater biological activity, including superior
      antioxidant activity. Yet, whilst the majority of animals produce equol following
      soy consumption, as much as 30-50 % of the adult human population cannot. This
      inability to produce equol in as much as half the population is thought to
      provide some explanation for the failure of soy to reveal any substantial health
      benefits in clinical studies. This article will comprehensively review literature
      investigating the potential cardiovascular benefits of daidzein and its
      metabolites, paying particular attention to equol. It will focus on the relative
      vasorelaxant activity, effects on nitric oxide synthase (NOS), antioxidant
      activity and potential for the treatment and prevention of hypertension and
      stroke. Findings obtained in both animal and human studies will be reviewed with
      the hope of gaining an insight into the experimental and clinical importance of
      equol to the cardiovascular benefits of soy.

PMID- 18045129
TI  - Synthetic peptides: the future of patient management in systemic rheumatic
      diseases?
AB  - Since the first description of self-reactive antibodies in systemic autoimmune
      rheumatic diseases, many autoantigens have been identified as useful diagnostic
      biomarkers in clinical immunology. Among the autoantigens, double-stranded
      desoxoribonucleic acid (dsDNA), the Smith antigen (Sm), topoisomerase-I (topo-I),
      proliferating cell nuclear antigen (PCNA), and others were described as hallmark
      targets of systemic autoimmune diseases. The detection of the corresponding
      autoantibodies can be performed with a variety of immunoassays based on native
      antigens, recombinant proteins or synthetic peptides. As discussed in this
      review, synthetic peptides often represent highly accurate antigenic ligands for
      autoantibody assays that can be easily produced in high quality and quantity and
      with remarkable reproducibility. Furthermore, the use of peptides that focus on
      abrogation or neutralization of pathogenic autoantibodies provides a possible new
      therapeutic approach to the management of autoimmune disorders. There is an
      increasing number of interesting examples for the application of synthetic
      peptides in diagnostic approaches. Today's sophisticated epitope mapping methods
      will potentate the identification of further peptides that can be possibly used
      as specific targets in diagnostic and therapeutic approaches to improve the
      patients treatment. This may lead to a new scientific research area with high
      impact on the development of diagnostic and therapeutic products, to the area of
      peptide engineering and "theranostics".

PMID- 18045130
TI  - Anti-cancer therapeutic approaches based on intracellular and extracellular heat
      shock proteins.
AB  - Stress or heat shock proteins (Hsps) Hsp90, Hsp70 and Hsp27 are chaperones that
      assist the proteins in their folding, stability, assembly into multi-protein
      complexes and transport across cellular membranes. The expression of some of them
      is highly induced in response to a wide variety of physiological and
      environmental insults. Hsps have a dual function depending on their intracellular
      or extracellular location. Intracellular Hsps have a protective function. They
      allow the cells to survive to lethal conditions. The cytoprotective functions of
      Hsps can largely explain by their anti-apoptotic properties. Hsp90, Hsp70 and
      Hsp27 can directly interact with different proteins of the tightly regulated
      programmed cell death machinery and thereby block the apoptotic process at
      distinct key points. In cancer cells, where the expression of Hsp27, Hsp70 and/or
      Hsp90 is frequently abnormally high, they participate in oncogenesis and in
      resistance to chemotherapy. Therefore, the inhibition of Hsps has become an
      interesting strategy in cancer therapy. In contrast to intracellular Hsps,
      extracellular located or membrane-bound Hsps mediate immunological functions.
      They can elicit an immune response modulated either by the adaptive or innate
      immune system. In cancer, most immunotherapeutical approaches based on
      extracellular Hsps exploit their carrier function for immunogenic peptides. This
      review will discuss this different and often paradoxical approaches in cancer
      therapy based on the dual role of Hsps, protective/tumorigenic versus
      immunogenic.

PMID- 18045131
TI  - Role of the APP non-amyloidogenic signaling pathway and targeting alpha-secretase
      as an alternative drug target for treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia, and its
      effective disease modifying therapies are desperately needed. Promotion of non
      amyloidogenic alpha-secretase cleavage of amyloid precursor protein (APP) to
      release soluble sAPPalpha, based on the most widely accepted "amyloid model" as a
      plausible mechanism for AD treatment, is the focus of this review. Modulation of
      alpha-secretase or "a disintegrin and metalloprotease (ADAM)"s activity via
      protein kinase C (PKC), calcium ion (Ca(2+)), tyrosine kinase (TK), MAP kinase
      (MAPK), and hormonal signaling, which regulate catabolic processing of APP, are
      discussed. The inhibition of amyloidogenic processing of APP by the beta- and
      gamma-secretase has been considered till now a promising strategy to treat AD.
      But beta- and gamma-secretase inhibitors, along with the available therapeutic
      tools for AD, have side effects. These challenges can be circumvented to certain
      extent; but activation of sAPPalpha release appears to be a potential alternative
      strategy to reduce cerebral amyloidosis. Drug screens have been performed to
      identify therapeutics for AD, but an effective screening strategy to isolate
      activators of alpha-secretase has been rarely reported. Novel reporter-based
      screens targeted toward APP mRNA 5' untranslated region (UTR), followed by
      counter-screens to detect alpha-secretase stimulators, could be important in
      detecting compounds to promote sAPPalpha release and reduce amyloid beta (Abeta)
      buildup. The primary inflammatory cytokine interleukin-1, which stimulates APP
      5'UTR-directed translation of cell-associated APP, enhances processing to
      sAPPalpha in astrocytes and co-activates ADAM-10/ADAM-17 through MAPK signaling;
      thus illustrating a novel pathway that could serve as therapeutic model for AD.

PMID- 18045132
TI  - Manipulation of microglial activation as a therapeutic strategy in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is the leading cause of dementia. Although the etiology
      of AD remains controversial, the amyloid hypothesis suggests that beta-amyloid
      (Abeta) peptides may contribute to brain dysfunction, and microglial activation
      has become increasingly regarded as a potential contributor to disease
      pathogenesis. Microglial activation is characterized by morphological changes and
      by production of various effectors, and activated neuroinflammation concurrent
      with increased oxidative stress may contribute to damage to neurons. However,
      recently there has been a recognition that microglia may also play a
      neuroprotective role through their release of neurotrophic factors and through
      phagocytosis of Abeta. Thus, there is growing consensus that a favorable
      combination of diminished microglia-mediated neuroinflammation and enhanced Abeta
      clearance may be critical in AD therapy. In this review, we will discuss the role
      of microglial activation in AD and how pharmacologic manipulation of microglia
      might bear upon the treatment of AD.

PMID- 18045133
TI  - Recent progress in rational drug design of neuraminidase inhibitors.
AB  - Neuraminidase is a major glycoprotein of influenza virus which is essential for
      viral infection and offers a potential target for antiviral drug development.
      Rational drug design of NA inhibitors is now in the clinic and these molecules
      are effective and safe for the treatment of influenza. Recently, research of
      structure-based NA inhibitors is becoming an interesting field, leading to a
      breakthrough in the control of influenza. Here we review the progress in the
      rational drug design of NA inhibitors in recent years.

PMID- 18045134
TI  - Apoptotic cell clearance and autoimmune disorder.
AB  - In multicellular organisms, unnecessary or harmful cells, such as those that are
      cancerous or infected with a virus, are eliminated by apoptosis. After apoptosis,
      cell corpses are rapidly recognized and phagocytosed by professional phagocytes,
      such as macrophages and dendritic cells. The rapid removal of cell corpses by
      phagocytes prevents the release of potentially toxic or immunogenic materials
      from dying cells. Although a number of molecules on phagocytes have been found to
      be involved in apoptotic cell clearance in vitro, only a few have been proved to
      be involved in apoptotic cell clearance in vivo by analyses of knockout animals.
      These knockout mice commonly suffer from autoimmunity, indicating that the
      complete removal of apoptotic cells is essential for the maintenance of self
      tolerance. In this review, we present an overview of the molecular mechanisms of
      apoptotic cell clearance by phagocytes and the pathological relevance of the
      failure of apoptotic cell clearance to autoimmune disorder.

PMID- 18045135
TI  - A needle-free approach for topical immunization: antigen delivery via vesicular
      carrier system(s).
AB  - Topical immunization (TI) is novel and needle free strategy involving vaccine
      delivery through topical application of antigen and adjuvant(s) directly or via a
      suitable carrier system on intact skin. Anatomy and physiology of skin attracts
      scientists in developing topical carrier system(s) for enhanced delivery of
      bioactive(s). Numerous techniques i.e. physical, chemical and vesicular carrier
      systems have been exploited for topical immunization. The present review discuss
      various vesicular systems i.e. liposomes, niosomes, transfersomes, vesosomes etc.
      for the efficient topical delivery of various immunogens along with comparative
      points of their merit(s) in TI. The mechanism of permeation of bioactive(s)
      through skin route via these carriers to the immune system for development of
      both cellular and humeral immunity has also been discussed. Moreover, the effect
      of composition and type of carrier system on type of immunity induced has also
      been focused to develop new effective carrier system(s) for topical immunization.

PMID- 18045136
TI  - Interaction of proteins with lipid rafts through glycolipid-binding domains:
      biochemical background and potential therapeutic applications.
AB  - The wide biochemical diversity of glycolipids in membranes explains why these
      molecules are often selected by pathogens (viruses, bacteria, prions) as primary
      sites of interactions with the cell surface. Moreover, glycolipids concentrate
      into cholesterol/glycolipid-rich microdomains where they can reach high local
      concentrations consistent with the multivalent attachment of pathogens on the
      cell surface. Finally, recent studies have shown that glycolipids could also
      modulate protein conformation. This chaperone activity of glycolipids has been
      associated with various pathogenic processes including HIV infection, prion
      propagation, and amyloid aggregation in Alzheimer's and Creutzfeldt-Jakob's
      diseases. Despite the potential interest for drugs mimicking glycolipid structure
      and function, the physicochemical properties of authentic glycolipids suggested
      that it might be difficult to obtain synthetic glycolipid analogues able to
      neutralise those pathogens before they could reach the cell surface. Recent data
      obtained with mono-, di-, and tri-hexosylceramide (GalCer, LacCer and Gb(3)) have
      proven that this was absolutely not the case and that highly active inhibitors
      could be designed through slight modifications of glycolipid structure.
      Biochemical studies of glycolipid-protein interactions have highlighted the
      importance of CH-pi stacking interactions between galactosyl head groups of the
      glycolipid and aromatic amino acids of the protein. The discovery of this unique
      mechanism of interaction may allow a rational strategy for the design and
      synthesis of glycolipid-based molecules as new anti-infectious and/or anti
      amyloidogenesis compounds. This strategy, which takes into account the
      hierarchical organisation of glycolipids into discrete membrane microdomains as
      well as their association with cholesterol, is discussed in the present review.

PMID- 18045137
TI  - Estrogens and glucocorticoid hormones in adipose tissue metabolism.
AB  - Women have a higher percentage of body fat than men, and there is a gender
      specific difference in fat distribution: Females tend to accumulate fat around
      the hips, buttocks, and thighs while men have a larger intra-abdominal (visceral)
      fat mass. After menopause, there is a redistribution of fat depots, and post
      menopausal women develop increased amounts of visceral fat. The risk of
      developing obesity-related diseases is significantly lower in pre-menopausal
      women compared to men, a difference that is abolished after menopause, suggesting
      that the female sex steroid estrogen influences adipogenesis and adipose
      metabolism. Experimentally, estrogen increases the size and number of
      subcutaneous adipocytes and attenuates lipolysis. Post-menopausal women also
      develop a more atherogenic lipid pattern and decreased levels of the
      prothrombotic protein plasminogen activator inhibitor-1, which attenuates
      fibrinolysis. Pathologically increased circulating cortisol concentration is
      associated with dysmetabolic features e.g., central obesity, elevated blood
      pressure, insulin resistance, and dyslipidemia. In "simple obesity,"
      glucocorticoid production is elevated. Peak levels of circulating cortisol are
      however low or normal, possibly because of increased clearance and/or tissue
      specific changes in cortisol production. In addition to the adrenal production of
      cortisol, cortisol is also generated in adipose tissue by the enzyme 11beta
      hydroxysteroid dehydrogenase type 1 (11betaHSD1) which converts inactive
      cortisone to active cortisol. The enzyme activity in subcutaneous fat increases
      with increasing body weight. Estrogen seems to have a tissue-specific influence
      on 11betaHSD1 enzyme activity, attenuating it in liver, kidney, and testis but
      upregulating 11betaHSD1 mRNA expression in preadipocytes from women. In the
      present review, we summarize and discuss the interaction between glucocorticoids
      and sex steroids and their influence on adipocyte metabolism.

PMID- 18045138
TI  - Fibrinogen signal transduction as a mediator and therapeutic target in
      inflammation: lessons from multiple sclerosis.
AB  - The blood protein fibrinogen as a ligand for integrin and non-integrin receptors
      functions as the molecular nexus of coagulation, inflammation and immunity.
      Studies in animal models and in human disease have demonstrated that
      extravascular fibrinogen that is deposited in tissues upon vascular rupture is
      not merely a marker, but a mediator of diseases with an inflammatory component,
      such as rheumatoid arthritis, multiple sclerosis, sepsis, myocardial infarction
      and bacterial infection. The present article focuses on the recent discoveries of
      specific cellular targets and receptors for fibrinogen within tissues that have
      extended the role of fibrinogen from a coagulation factor to a regulator of
      inflammation and immunity. Fibrinogen has the potential for selective drug
      targeting that would target its proinflammatory properties without affecting its
      beneficial effects in hemostasis, since it interacts with different receptors to
      mediate blood coagulation and inflammation. Strategies to target receptors for
      fibrinogen and fibrin within the tissue microenvironment could reveal selective
      and disease-specific agents for therapeutic intervention in a variety of human
      diseases associated with fibrin deposition.

PMID- 18045139
TI  - Cochlear stem cells/progenitors and degenerative hearing disorders.
AB  - Hearing loss (deafness) affects approximately 250 million people globally. The
      major cause of deafness is loss of hair cells and spiral ganglion neurons due to
      aging, antibiotic use, noise exposure, and genetic defects. At the present time,
      there is no effective method for restoration of hearing biologically. Cochlear
      stem cells/progenitors (CSCs), quiescent in the organ of Corti, are excellent
      candidates for restoration of cell types in the organ of Corti biologically.
      However, little is known about the biology of CSCs and developmental cues for
      CSCs to differentiate into hair cells and neurons at the present time. In this
      article, we briefly reviewed the isolation of CSCs from the postnatal organ of
      Corti in mice and their capability to differentiate into hair cells and neurons
      in vitro under the guidance of a group of growth factors: sonic hedgehog (SHH),
      epidermal growth factor (EGF), retinoic acid (RA), and brain-derived neurotrophic
      factor (BDNF), herein termed SERB. The identification of CSCs and their
      differentiation signals is potentially of clinical importance.

PMID- 18045140
TI  - Nanotechnology as an adjunct tool for transplanting engineered cells and tissues.
AB  - Laboratory and clinical studies have provided evidence of feasibility, safety and
      efficacy of cell transplantation to treat a wide variety of diseases
      characterized by tissue and cell dysfunction ranging from diabetes to spinal cord
      injury. However, major hurdles remain and limit pursuing large clinical trials,
      including the availability of a universal cell source that can be differentiated
      into specific cellular phenotypes, methods to protect the transplanted allogeneic
      or xenogeneic cells from rejection by the host immune system, techniques to
      enhance cellular integration of the transplant within the host tissue, strategies
      for in vivo detection and monitoring of the cellular implants, and new techniques
      to deliver genes to cells without eliciting a host immune response. Finding ways
      to circumvent these obstacles will benefit considerably from being able to
      understand, visualize, and control cellular interactions at a sub-micron level.
      Cutting-edge discoveries in the multidisciplinary field of nanotechnology have
      provided us a platform to manipulate materials, tissues, cells, and DNA at the
      level of and within the individual cell. Clearly, the scientific innovations
      achieved with nanotechnology are a welcome strategy for enhancing the generally
      encouraging results already achieved in cell transplantation. This review article
      discusses recent progress in the field of nanotechnology as a tool for tissue
      engineering, gene therapy, cell immunoisolation, and cell imaging, highlighting
      its direct applications in cell transplantation therapy.

PMID- 18045141
TI  - Nuclear factor-kappa B: from clone to clinic.
AB  - Nuclear transcription factor kappaB (NF-kappaB) was first discovered in 1986 in
      the nucleus of the B cell as an enhancer in the kappa immunoglobulin chain.
      However, this factor has identified in the cytoplasm in the resting state. When
      activated in response to inflammatory stimuli, carcinogens, stress, ionizing
      radiation, and growth factors; NF-kappaB translocates to the nucleus where it
      upregulates the expression of over 400 different gene products linked with
      inflammation, cell survival, proliferation, invasion, and angiogenesis. The
      activation of NF-kappaB has now been linked with a variety of inflammatory
      diseases, including cancer and pulmonary, autoimmune, skin, neurodegenerative,
      and cardiovascular disorders. Indeed, constitutive NF-kappaB activation
      frequently correlates with the proliferation, survival, chemoresistance,
      radioresistance, and progression of various cancers. Hence, NF-kappaB has both
      diagnostic and prognostic applications. In addition, pharmaceutical companies are
      aggressively pursuing development of inhibitors of NF-kappaB with therapeutic
      potential. Thus within last decades this transcription factor, discovered
      serendipitously, has moved from "clone to clinic".

PMID- 18045142
TI  - The ability of melatonin to counteract lipid peroxidation in biological
      membranes.
AB  - This paper reviews recent data relevant to the antioxidant effects of melatonin
      with special emphasis on the changes produced in polyunsaturated fatty acids
      located in the phospholipids of biological membranes. The onset of lipid
      peroxidation within cellular membranes is associated with changes in their
      physicochemical properties and with the impairment of protein functions located
      in the membrane environment. All cellular membranes are especially vulnerable to
      oxidation due to their high concentration of polyunsaturated fatty acids. These
      processes combine to produce changes in the biophysical properties of membranes
      that can have profound effects on the activity of membrane-bound proteins. This
      review deals with aspects for lipid peroxidation of biological membranes in
      general, but with some emphasis on changes of polyunsaturated fatty acids, which
      arise most prominently in membranes and have been studied extensively in our
      laboratory. The article provides current information on the effect of melatonin
      on biological membranes, changes in fluidity, fatty acid composition and lipid
      protein modifications during the lipid peroxidation process of photoreceptor
      membranes and modulation of gene expression by the hormone and its preventive
      effects on adriamycin-induced lipid peroxidation in rat liver. Simple model
      systems have often been employed to measure the activity of antioxidants.
      Although such studies are important and essential to understand the mechanisms
      and kinetics of antioxidant action, it should be noted that the results of simple
      in vitro model experiments cannot be directly extrapolated to in vivo systems.
      For example, the antioxidant capacity of melatonin, one of the important
      physiological lipophilic antioxidants, in solution of pure triglycerides enriched
      in omega-3 polyunsaturated fatty acids is considerably different from that in
      subcellular membranes.

PMID- 18045143
TI  - DJ-1: a newcomer in Parkinson's disease pathology.
AB  - Parkinson's disease (PD) is a movement disorder of high prevalence in the
      elderly. It is characterized by a loss of dopaminergic neurons and the presence
      of intracytoplasmic inclusions named Lewy bodies. To date six familial PD
      associated proteins have been identified so far. Some of them are implicated in
      the development of either autosomal dominant (alpha-synuclein and LRRK2 (leucine
      rich repeat kinase 2/dardarin) or early-onset recessive (parkin, DJ-1, PINK1
      (PTEN-induced kinase-1) and ATP13A2) PD forms. A number of genetic studies have
      shown that 50% of the recessive forms are linked to mutations on parkin gene,
      followed by PINK1 (8-15%) and DJ-1 (1%). The purpose of this review is to provide
      an overview of the emerging data on the cellular and molecular biology of DJ-1.
      DJ-1 is a ubiquitous protein that was first described as an oncogene.
      Nevertheless, after its association to monogenic PD a number considerable data
      aiming at understanding its implication in the physiopathology of PD was
      produced. This review will describe the main advances concerning the function of
      DJ-1. A considerable progress that was only possible due to a better
      understanding of DJ-1 structure, genetics, distribution and development of in
      vivo models. All these points along with the description of recent data showing
      the interaction of DJ-1 with other PD-associated proteins will be given.

PMID- 18045144
TI  - Gamma delta T cells and dendritic cells: close partners and biological adjuvants
      for new therapies.
AB  - The knowledge of several signals influencing Dendritic Cell (DC) functions is
      crucial to manipulate the immune system for new vaccination therapies. Our recent
      findings provide a new model of intervention on DC system suggesting novel
      therapeutic implications. T, NK, and gammadelta T cell stimuli may enhance DC
      maturation, Th polarization and trigger the adaptive immune response. Regulatory
      effects of gammadelta T cells on inflammation and immune responses may be
      mediated by their interaction with DCs and they are analyzed in the last years in
      humans and mice. In humans, Vgamma9Vdelta2 T cells represent the most part of
      circulating gammadelta T cells and are activated by non-peptidic molecules
      derived from different microorganisms or abnormal metabolic routes. They share
      both NK-like and effector/memory T cell features, and among these the possibility
      to interact with DCs. Co-culture of immature DCs with activated Vgamma9Vdelta2 T
      cells allows DCs to acquire features of mature DCs complementing the migratory
      activity, up-regulating the chemokine receptors, and antigen presentation.
      Similarly to the NK-derived signals, DC activation is mostly mediated by soluble
      factors secreted by gammadelta T cells. Many non-peptidic molecules including
      nitrogen-containing bisphosphonates and pyrophosphomonoester drugs stimulate the
      activity of Vgamma9Vdelta2 T cells in vitro and in vivo. The relatively low in
      vivo toxicity of many of these drugs makes possible novel vaccine and immune
      based strategies, through DCs, for infectious and neoplastic diseases.

PMID- 18045145
TI  - Oxidative stress and the JNK pathway are involved in the development of type 1
      and type 2 diabetes.
AB  - Failure of pancreatic beta-cells is the common characteristic of type 1 and type
      2 diabetes. Type 1 diabetes mellitus is induced by destruction of pancreatic beta
      cells which is mediated by an autoimmune mechanism and consequent inflammatory
      process. Various inflammatory cytokines and oxidative stress are produced during
      this process, which has been proposed to play an important role in mediating beta
      cell destruction. The JNK pathway is also activated by such cytokines and
      oxidative stress, and is involved in beta-cell destruction. Type 2 diabetes is
      the most prevalent and serious metabolic disease, and beta-cell dysfunction and
      insulin resistance are the hallmark of type 2 diabetes. Under diabetic
      conditions, chronic hyperglycemia gradually deteriorates beta-cell function and
      aggravates insulin resistance. This process is called "glucose toxicity". Under
      such conditions, oxidative stress is provoked and the JNK pathway is activated,
      which is likely involved in pancreatic beta-cells dysfunction and insulin
      resistance. In addition, oxidative stress and activation of the JNK pathway are
      also involved in the progression of atherosclerosis which is often observed under
      diabetic conditions. Taken together, it is likely that oxidative stress and
      subsequent activation of the JNK pathway are involved in the pathogenesis of type
      1 and type 2 diabetes.

PMID- 18045146
TI  - Molecular and cellular mechanisms for Alzheimer's disease: understanding APP
      metabolism.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease associated
      with aging. One important pathologic feature of AD is the formation of
      extracellular senile plaques in the brain, whose major components are small
      peptides called beta-amyloid (Abeta) that are derived from beta-amyloid precursor
      protein (APP) through sequential cleavages by beta-secretase and gamma-secretase.
      Because of the critical role of Abeta in the pathogenesis of AD, unraveling the
      cellular and molecular events underlying APP/Abeta metabolism has been and
      remains, of paramount importance to AD research. In this article we will focus on
      the regulation of APP metabolism leading to Abeta generation. We will review
      current knowledge of the secretases (alpha-, beta-, and gamma-secretases)
      involved in APP processing and various molecular and cellular mechanisms
      underlying intracellular trafficking of APP, which is a highly regulated process
      and whose disturbance has direct impacts on the production of Abeta.

PMID- 18045147
TI  - Advanced glycation end products, oxidative stress and metalloproteinases are
      altered in the cerebral microvasculature during aging.
AB  - Biological aging is associated with an increased incidence of cerebrovascular
      disease. Recent findings indicate that oxidative stress promoting age-related
      changes of cerebral circulation are involved in neurodegenerative disorders such
      as Alzheimer's disease (AD) and Parkinson's disease. The aim of this study was to
      evaluate the contribution of cerebral microvessels to the oxidative stress during
      brain aging, by: (i) assessment of precursors for advanced glycation end products
      (AGE) formation, (ii) activities of antioxidant enzymes, namely superoxide
      dismutase (SOD), glutathione peroxidase (GPx) and glutathione disulfide reductase
      (GR), and (iii) the activities of metalloproteinases (MMPs), MMP-2 and MMP-9,
      involved in synaptogenesis and memory consolidation. The experiments were
      performed on two groups of male Wistar rats: 15 young (3-6 months old) and 15
      aged (18-24 months old) animals. The cerebral microvessels were isolated by
      mechanical homogenization, the concentration of protein carbonyls and the
      activity of antioxidant enzymes were evaluated by spectrophotometry, and gelatin
      SDS-PAGE zymography was employed to evaluate MMP-2 and MMP-9 activities. The
      results showed that, by comparison with young rats, aged brain microvessels
      contain: (i) approximately 106 % increase of protein carbonyls production; (ii)
      approximately 68% higher GPx activity, unmodified activities of SOD and GR; (iii)
      approximately 30% diminishment in MMP-2 activity, and the specific occurrence of
      MMP-9 enzyme. The data suggest that the age-related changes of microvessels could
      increase the propensity for cerebral diseases and might represent, at least in
      part, a prerequisite for the deterioration of mental and physical status in the
      elderly.

PMID- 18045148
TI  - Clozapine and olanzapine but not risperidone impair the pre-frontal striatal
      system in relation to egocentric spatial orientation in a Y-maze.
AB  - Many studies indicate a dissociation between two forms of orientation:
      allocentric orientation, in which an organism orients on the basis of cues
      external to the organism, and egocentric spatial orientation (ESO) by which an
      organism orients on the basis of proprioceptive information. While allocentric
      orientation is mediated primarily by the hippocampus and its afferent and
      efferent connections, ESO is mediated by the prefronto-striatal system. Striatal
      lesions as well as classical neuroleptics, which block dopamine receptors, act
      through the prefronto-striatal system and impair ESO. The purpose of the present
      study was to determine the effects of the atypical antipsychotics clozapine,
      olanzapine and risperidone which are believed to exert its antipsychotic effects
      mainly by dopaminergic, cholinergic and serotonergic mechanisms. A delayed-two
      alternative-choice-task, under conditions that required ESO and at the same time
      excluded allocentric spatial orientation was used. Clozapine and olanzapine
      treated rats made more errors than risperidone treated rats in the delayed
      alternation in comparison with the controls. Motor abilities were not impaired by
      any of the drugs. Thus, with regard to the delayed alternation requiring ESO,
      clozapine and olanzapine but not risperidone affects the prefronto-striatal
      system in a similar way as classical neuroleptics does.

PMID- 18045149
TI  - Clearance of amyloid-beta peptide by neuronal and non-neuronal cells: proteolytic
      degradation by secreted and membrane associated proteases.
AB  - Deposition of amyloid-beta peptide (Abeta) in the brain is an early and invariant
      feature of all forms of Alzheimer's disease (AD). As for all proteins or
      peptides, the steady-state level of Abeta peptide is determined not only by its
      production, but also by its degradation. So, overactive proteases involved in
      generating Abeta from amyloid precursor protein or underactive Abeta-degrading
      enzymes could lead to abnormal Abeta deposition in the brain. Since in the
      sporadic forms of AD (90% of all AD cases) an impaired clearance of Abeta appears
      to be at the origin of its aggregation and tissue deposition, we have
      investigated its proteolytic degradation by several neuronal and non-neuronal
      cells. In this report, we show that these cell types exhibit a similar profile of
      Abeta-degradation by cell-surface and secreted proteases which were respectively
      characterized as metallo- and serine proteases. By using a combination of the
      liquid chromatography/on-line mass spectrometry, we demonstrate that: (i)-the
      membrane associated protease(s) hydrolizes Abeta40 essentially at Lys(28)
      Gly(29), Phe(19) Phe(20) and Val(18) Phe(19) bonds; and (ii)-the secreted
      protease(s) cleaves the generating fragments Abeta (1-28), Abeta (1-19), Abeta (1
      18) at His(14) Gln(15) bond and also Abeta (1-28) at Phe(20) Ala(21) and Asp(23)
      Val(24) sites. This is the first time our results define a proteolytic
      degradation process of Abeta40 that appears to be independent of the cell type
      and may represent a general pattern of its enzymatic clearance.

PMID- 18045150
TI  - Intracranial venous haemodynamics in multiple sclerosis.
AB  - In multiple sclerosis (MS) plaques are known to be venocentric; in addition, MS
      lesions and peripheral venous disorders share a number of key features. To date,
      however, despite the anatomical relationship between MS lesions and the venous
      system, no information on the intracranial venous haemodynamics of MS is
      available. Eighty-nine consecutive MS patients (58 relapsing-remitting, 31
      secondary progressive) matched with 60 controls underwent transcranial color
      coded duplex sonography (TCCS). We assessed, in supine as well as in sitting
      positions, the direction of flow at the activation of the thoracic pump in the
      deep middle cerebral veins (dMCVs), and in the transverse sinus (TS). In the
      dMCVs, we also measured peak systolic velocity (PSV), peak diastolic velocity
      (PDV), as well as the resistance index (RI). Reflux/bidirectional flow rate was
      significantly higher in the MS population determining also significant
      differences in PDV, characterized by negative values (16.2+/-1 cm/sec in controls
      vs. -1.3 +/-2.6 cm/sec in MS, respectively, p<0.0001). Consequently, RI was
      dramatically increased in the MS group, affecting impedance of cerebral venous
      drainage (0.48+/-0.04 in controls vs. 1.1 +/-0.08 in MS, respectively p<0.0001).
      Therefore, the detection of reflux directed toward the subcortical grey matter
      was significantly associated to highest disability scores (p < 0.0001). Our study
      of MS patients demonstrated significant haemodynamic alterations detected in
      veins anatomically related to plaque disposition. Our findings should contribute
      towards understanding the role of altered venous flow and tissue drainage in the
      MS inflammatory chain, as well as in the neurodegenerative process.

PMID- 18045151
TI  - Effects of an acute treatment with L-thyroxine on memory, habituation, danger
      avoidance, and on Na+, K+ -ATPase activity in rat brain.
AB  - Thyroid hormones (THs) have a relevant action on brain development and
      maintenance. By using an acute treatment to induce a hyperthyroid animal model,
      we aimed at investigating the effect of an altered THs levels on learning and
      memory and on the activity of Na(+), K(+)-ATPase in the rat brain. Our results
      have shown that the acute treatment with L-T4 did not alter the retrieval of the
      inhibitory avoidance task, but had a significant effect on the elevated plus maze
      and on open-field performance in rats. We suggest that animals subjected to L-T4
      administration improved the habituation to a novel environment as well as a
      better evaluation of a dangerous environment, respectively. Na(+), K(+)-ATPase
      activity is increased in parietal cortex (30%), but it is not altered in
      hippocampus in L-T4 treated group. These both brain structures are involved in
      memory processing and it was previously demonstrated that there is a double
      dissociation between them for spatial location information, perceptual and
      episodic memory. We propose the hypothesis that this increase of Na(+), K(+)
      ATPase activity in parietal cortex may be correlated to our results in behavior
      tests, which suggest a role of THs as well as of the Na(+), K(+)-ATPase in the
      cognitive process.

PMID- 18045152
TI  - Macrophage infiltration, lectin-like oxidized-LDL receptor-1, and monocyte
      chemoattractant protein-1 are reduced by chronic HMG-CoA reductase inhibition.
AB  - Statin reduces cerebrovascular events independent of its cholesterol lowering
      effect. We hypothesized that statin inhibits early atherosclerotic change in
      common carotid artery (CCA), and investigated its effect on lectin-like oxidized
      LDL receptor-1 (LOX-1) and monocyte chemoattractant protein-1 (MCP-1) expression,
      both of which are early atherosclerotic markers. Stroke-prone spontaneous
      hypertensive rats (SHR-SP) of 8 weeks old were orally treated with vehicle or
      simvastatin (20mg/kg) daily. After 4 weeks of simvastatin or vehicle treatment,
      or 2 weeks of vehicle and 2 weeks of simvastatin treatment, CCA was removed. LOX
      1 and MCP-1 expression as well as macrophage infiltration were histologically
      investigated. Lipid deposition was also investigated by Sudan III staining.
      Simvastatin groups showed significantly smaller amount of lipid deposition and
      LOX-1 and MCP-1 expression, independent of serum lipid levels. Macrophage
      infiltration was also decreased. Reduction of cerebrovascular events by statins
      may be brought by the direct inhibition of atherosclerotic change.

PMID- 18045153
TI  - Increased neuronal injury in transgenic mice with neuronal overexpression of
      human cyclooxygenase-2 is reversed by hypothermia and rofecoxib treatment.
AB  - Cyclooxygenase-2 (COX-2) is up-regulated during ischemia. However, the role of
      COX-2 in neuronal injury is still unclear. In this study we tested whether
      neuronal overexpression of human COX-2 in a transgenic mouse model potentiates
      neuronal injury after global ischemic insult. Further, we tested whether the
      neuronal injury could be ameliorated by intra-ischemic mild hypothermia (33-34
      degrees C) alone or in combination with diet treatment of rofecoxib, a COX-2
      specific inhibitor. Global ischemia with intra-ischemic normothermia (36-37
      degrees C) resulted in significantly higher neuronal damage in the CA1 region of
      hippocampus of transgenic mice than in wild type controls, confirming a
      deleterious role of COX-2 in ischemic neuronal damage. Hypothermia significantly
      reduced neuronal damage in both transgenic mice and wild type controls to the
      same extent, suggesting that the aggravating effect of COX-2 could be largely
      eliminated by hypothermia. When hypothermia was combined with rofecoxib
      treatment, neuronal damage was further reduced in response to global ischemia.
      The results suggest that COX-2 inhibition by prophylactic treatment with
      rofecoxib coupled with hypothermia at the time of acute stroke insult could be an
      effective therapeutic approach in early stages of stroke treatment in high risk
      patients.

PMID- 18045154
TI  - Alterations in cerebral metabolomics and proteomic expression during sepsis.
AB  - The cause of brain dysfunction during sepsis and septic encephalopathy is still
      under ongoing research. Sepsis induced changes in cerebral protein expression may
      play a significant role in the understanding of septic encephalopathy. The aim of
      the present study was to explore cerebral proteome alterations in septic rats.
      Fifty-six male Wistar rats were randomly assigned to a sepsis group (coecal
      ligature and puncture, CLP) or a control group (sham). Surviving rats were killed
      24 or 48 hours after surgery and whole-brain lysates were used for two
      dimensional gel electrophoresis and subsequent protein identification.
      Differentially expressed proteins were identified by mass spectrometry. Using the
      Ingenuity Pathways Analysis (IPA) tool, the relationship and interaction between
      the identified proteins was analyzed. Mortality was 53 % in septic rats. No rat
      of the control group was lost. More than 1,100 spots per gel were discriminated
      of which 29 different proteins were significantly (2-fold, P<0.01) changed: 24
      proteins down-regulated after 24 hours; two proteins up-regulated and three down
      regulated after 48 hours. IPA identified 11 of 35 differentially regulated
      proteins allocating them to an existing inflammatory pathway. In the analysis of
      septic rat brains, multiple differentially expressed proteins associated with
      metabolism, signaling, and cell stress can be identified via proteome analysis,
      that may help to understand the development of septic encephalopathy.

PMID- 18045155
TI  - Cardiac dys-synchronization and arrhythmia in hyperhomocysteinemia.
AB  - Although cardiac synchronization is important in maintaining myocardial
      performance, the mechanism of dys-synchronization in ailing to failing myocardium
      is unclear. It is known that the cardiac myocyte contracts and relaxes
      individually; however, it synchronizes only when connected to one another by low
      resistance communications called gap junction protein (connexins) and extra
      cellular matrix (ECM). Therefore, the remodeling of connexins and ECM in heart
      failure plays an important role in cardiac conduction, synchronization and
      arrhythmias. This review for the first time addresses the role of systemic
      accumulation of homocysteine (Hcy) in vasospasm, pressure and volume overload
      heart failure, hypertension and cardiac arrhythmias. The attenuation of calcium
      dependent mitochondrial (mt), endothelial and neuronal nitric oxide synthase
      (mtNOS, eNOS and nNOS) by Hcy plays a significant role in cardiac arrhythmias.
      The signal transduction mechanisms in Hcy-induced matrix metalloproteinase (MMP)
      activation in cardiac connexin remodeling are discussed.

PMID- 18045158
TI  - Neurogenesis in the adult brain: implications for Alzheimer's disease.
AB  - The function of neurogenesis in the adult brain is still unknown. Interventions
      such as environmental enrichment and exercise impinge on neurogenesis, suggesting
      that the process is regulated by experience. Conversely, a role for neurogenesis
      in learning has been proposed through 'cellular plasticity', a process akin to
      synaptic plasticity but operating at the network level. Although neurogenesis is
      stimulated by acute injury, and possibly by neurodegenerative processes such as
      Alzheimer's disease (AD), it does not suffice to restore function. While the role
      and direction of change in the neurogenic response at different stages of AD is
      still a matter of debate, it is possible that a deficit in neurogenesis may
      contribute to AD pathogenesis since at least one of the two regions ostensibly
      neurogenic in the adult human brain (the subgranular zone of the dentage gyrus
      and the ventriculo-olfactory neurogenic system) support high-level functions
      affected in early AD (associative memory and olfaction respectively). The age of
      onset and the rate of progression of sporadic forms of AD are highly variable.
      Sporadic AD may have a component of insufficient neurogenic replacement or
      insufficient neurogenic stimulation that is correlated with traits of personal
      history; the rate of neurogenesis and the survival of replicating progenitors is
      strongly modified by behavioral interventions known to impinge on the rate of
      neurogenesis and the probability of survival of newly born neurons--exercise,
      enriched experience, and learning. This view is consistent with epidemiological
      data suggesting that higher education and increased participation in
      intellectual, social and physical aspects of daily life are associated with
      slower cognitive decline in healthy elderly ("cognitive reserve") and may reduce
      the risk of AD. Although neurogenesis can be modulated exogenously by growth
      factors, stimulation of neurogenesis as a mean to treat neurodegeneration is
      still for the most part speculative. Moreover, it is possible that different
      roles of neurogenesis during the course of AD are dictated by the degree of
      permissibility of the environment in which the process is taking place. A unique
      opportunity may exist in which the therapeutic stimulation of neurogenesis might
      contribute to functional 'repair' of the adult diseased brain, before damage to
      whole neuronal networks has ensued. In spite of the considerable gaps in our
      knowledge of neurogenesis, and of the considerable limitations that will need to
      be overcome before we can intervene in the process, that new neurons are added
      continuously to the adult mammalian brain is a discovery that has already changed
      the way we think about neurobiology, and may soon change the way we understand
      and approach neurodegenerative diseases such as AD.

PMID- 18045159
TI  - Regulation of neurogenesis and gliogenesis by stress and antidepressant
      treatment.
AB  - Structural and morphological changes in limbic brain regions are associated with
      depression, chronic stress and antidepressant treatment, and increasing evidence
      supports the hypothesis that dysregulation of cell proliferation contributes to
      these effects. We review the morphological alterations observed in two brain
      regions implicated in mood disorders, the prefrontal cortex and hippocampus, and
      discuss the similarities and differences of the cellular consequences of chronic
      stress. We briefly discuss the proposed mechanisms implicated in neuroplasticity
      impairments that result from stress and that contribute to mood disorders, with a
      particular interest in adult neurogenesis and gliogenesis. This information has
      contributed to novel antidepressant medication development that utilizes adult
      neurogenesis and gliogenesis as preclinical cellular markers for predicting
      antidepressant properties of novel compounds.

PMID- 18045156
TI  - "Sly as a FOXO": new paths with Forkhead signaling in the brain.
AB  - The Forkhead transcription factor FOXO3a has emerged as a versatile target for
      diseases that impact upon neuronal survival, vascular integrity, immune function,
      and cellular metabolism. Enthusiasm is high to fill a critical treatment void
      through FOXO3a signaling for several neurodegenerative disorders that include
      aging, neuromuscular disease, systemic lupus erythematosus, stroke, and diabetic
      complications. Here we discuss the influence of FOXO3a upon cell survival and
      longevity, the intricate signal transduction pathways of FOXO3a, insights into
      present disease models, and the potential clinical translation of FOXO3a
      signaling into novel therapeutic strategies.

PMID- 18045160
TI  - Neurogenesis and stroke.
AB  - Stroke stimulates neurogenesis in select regions of the adult brain, and the
      newborn neurons that result can migrate to areas of ischemic injury, where they
      may have the capacity to enhance brain recovery. These observations suggest that
      stroke-induced neurogenesis may contribute to endogenous brain repair after
      stroke, and that the mechanisms that underlie neurogenesis may represent
      potential therapeutic targets. Alternatively, transplantation of exogenously
      derived neural cells might also be an approach to the treatment of stroke.

PMID- 18045161
TI  - Adult neurogenesis and Parkinson's disease.
AB  - Parkinson's disease is a neurodegenerative disorder characterized by a
      progressive neuronal loss affecting preferentially the dopaminergic neurons of
      the nigrostriatal projection. Transplantation of fetal dopaminergic precursor
      cells has provided the proof of principle that a cell replacement therapy can
      ameliorate clinical symptoms in affected patients. Recent years have provided
      evidence for the existence of neural stem cells with the potential to produce new
      neurons, particularly of a dopaminergic phenotype, in the adult mammalian brain.
      Such stem cells have been identified in so called neurogenic brain areas, where
      neurogenesis is constitutively ongoing, but also in primarily non-neurogenic
      areas, such as the midbrain and the striatum, where neurogenesis does not occur
      under normal physiological conditions. We review here presently published
      evidence to evaluate the concept that endogenous neural stem cells may have the
      potential to be instrumentalized for a non-invasive cell replacement therapy with
      autologous neurons to repair the damaged nigrostriatal dopaminergic projection in
      Parkinson's disease.

PMID- 18045162
TI  - Cellular niches for endogenous neural stem cells in the adult brain.
AB  - Neural stem cells are present throughout life and continuously give rise to new
      neurons and glia cells in the mammalian central nervous system. Accumulating
      evidence suggests essential roles of micro-environments, or niches, in supporting
      active neurogenesis from endogenous neural stem cells within restricted regions
      of the adult brain. These neurogenic niches also regulate different steps of
      adult neurogenesis in response to physiological and pathological stimulations.
      Recent studies have identified several cellular niche components, including
      endothelial cells, astroglia, ependymal cells, immature progeny of NSCs and
      mature neurons. In this review, we discuss identified niche signals from these
      cellular components in regulating different steps of adult neurogenesis. We also
      highlight some of the potential therapeutic targets to be manipulated within
      neurogenic niche for repair of the adult central nervous system.

PMID- 18045163
TI  - Could hippocampal neurogenesis be a future drug target for treating temporal lobe
      epilepsy?
AB  - The dentate gyrus, a region of the hippocampal formation, displays the highest
      level of plasticity in the brain and exhibits neurogenesis all through life.
      Dentate neurogenesis, believed to be essential for learning and memory function,
      responds to physiological stimuli as well as pathological situations. The role of
      dentate neurogenesis in the pathophysiology of temporal lobe epilepsy (TLE) has
      received increased attention lately because of its disparate response in the
      early and chronic stages of the disease. Acute seizures or status epilepticus
      immensely enhance dentate neurogenesis and lead to an aberrant migration of newly
      born neurons into the dentate hilus and the formation of epileptogenic circuitry
      in the injured hippocampus. Conversely, spontaneous recurrent seizures that arise
      during chronic TLE are associated with dramatically reduced dentate neurogenesis.
      In this review, we discuss the potential significance of enhanced but abnormal
      neurogenesis taking place shortly after brain injury or the status epilepticus
      towards the development of chronic epilepsy, and prospective implications of
      dramatically waned dentate neurogenesis occurring during chronic epilepsy for
      learning and memory function and depression in TLE. Furthermore, we confer
      whether hippocampal neurogenesis is a possible drug target for preventing TLE
      after brain injury or the status epilepticus, and for easing learning and memory
      impairments during chronic epileptic conditions. Additionally, we discuss some
      possible drugs and approaches that need to be evaluated in future in animal
      models of TLE to further understand the role of neurogenesis in the pathogenesis
      of TLE and whether modulation of neurogenesis is useful for treating TLE.

PMID- 18045164
TI  - Neurotransmitter regulation of adult neurogenesis: putative therapeutic targets.
AB  - The evidence that new neuron addition takes place in the mammalian brain
      throughout adult life has dramatically altered our perspective of the potential
      for plasticity in the adult CNS. Although several recent reports suggest a latent
      neurogenic capacity in multiple brain regions, the two major neurogenic niches
      that retain the ability to generate substantial numbers of new neurons in adult
      life are the subventricular zone (SVZ) lining the lateral ventricles and the
      subgranular zone (SGZ) in the hippocampal formation. The discovery of adult
      neurogenesis has also unveiled a novel therapeutic target for the repair of
      damaged neuronal circuits. In this regard, understanding the endogenous
      mechanisms that regulate adult neurogenesis holds promise both for a deeper
      understanding of this form of structural plasticity, as well as the
      identification of pathways that can serve as therapeutic targets to manipulate
      adult neurogenesis. The purpose of the present review is to discuss the
      regulation of adult neurogenesis by neurotransmitters and to highlight the
      relevance of these endogenous regulators as targets to modulate adult
      neurogenesis in a clinical context.

PMID- 18045165
TI  - Ion channels as a target for drug design.

PMID- 18045166
TI  - The impact of sub-cellular location and intracellular neuronal proteins on
      properties of GABA(A) receptors.
AB  - Most studies of GABA(A) receptor accessory proteins have focused on trafficking,
      clustering and phosphorylation state of the channel-forming subunits and as a
      result a number of proteins and mechanisms have been identified that can
      influence the GABA(A) channel expression and function in the cell plasma
      membrane. In the light of a growing list of intracellular and transmembrane
      neuronal proteins shown to affect the fate, function and pharmacology of the
      GABA(A) receptors in neurons, the concept of what constitutes the native GABA(A)
      receptor complex may need to be re-examined. It is perhaps more appropriate to
      consider the associated proteins or some of them to be parts of the receptor
      channel complex in the capacity of ancillary proteins. Here we highlight some of
      the effects the intracellular environment has on the GABA-activated channel
      function and pharmacology. The studies demonstrate the need for co-expression of
      accessory proteins with the GABA(A) channel-forming subunits in heterologous
      expression systems in order to obtain the full repertoire of GABA(A) receptors
      characteristics recorded in the native neuronal environment. Further studies e.g.
      on gene-modified animal models are needed for most of the accessory proteins to
      establish their significance in normal physiology and in pathophysiology of
      neurological and psychiatric diseases. The challenge remains to elucidate the
      effects that the accessory proteins and processes (e.g. phosphorylation) plus the
      sub-cellular location have on the "fine-tuning" of the functional and
      pharmacological properties of the GABA(A) receptor channels.

PMID- 18045167
TI  - Multiple modes of a-type potassium current regulation.
AB  - Voltage-dependent potassium (K+) channels (Kv) regulate cell excitability by
      controlling the movement of K+ ions across the membrane in response to changes in
      the cell voltage. The Kv family, which includes A-type channels, constitute the
      largest group of K+ channel genes within the superfamily of Na+, Ca2+ and K+
      voltage-gated channels. The name "A-type" stems from the typical profile of these
      currents that results form the opposing effects of fast activation and
      inactivation. In neuronal cells, A-type currents (I(A)), determine the interval
      between two consecutive action potentials during repetitive firing. In cardiac
      muscle, A-type currents (I(to)), control the initial repolarization of the
      myocardium. Structurally, A-type channels are tetramers of alpha-subunits each
      containing six putative transmembrane domains including a voltage-sensor. A-type
      channels can be modulated by means of protein-protein interactions with so-called
      beta-subunits that control inactivation voltage sensitivity and other properties,
      and by post-transcriptional modifications such as phosphorylation or oxidation.
      Recently a new mode of A-type regulation has been discovered in the form of a
      class of hybrid beta-subunits that posses their own enzymatic activity. Here, we
      review the biophysical and physiological properties of these multiple modes of A
      type channel regulation.

PMID- 18045168
TI  - The NMDA receptor/ion channel complex: a drug target for modulating synaptic
      plasticity and excitotoxicity.
AB  - A recent search on PubMed for the phrase NMDA receptor results in 2,190 hits on
      this topic for review articles and 20,100 hits for experimental papers. This is a
      direct reflection of the intensiveness, significance, and complexity associated
      with the research on this key receptor protein over the last several decades. In
      this review, we briefly describe the NMDA receptor structure, discuss the role of
      NMDA receptors in modulating synaptic plasticity and excitotoxicity, explore age
      dependent changes in NMDA receptor functioning, and survey interesting NMDA
      receptor blockers. Given the huge existing literature on the subject, an
      exhaustive review has not been endeavored. Instead, an attempt was made to point
      out those studies that have been instrumental in the field or that are of special
      interest.

PMID- 18045169
TI  - Developing new anti-arrhythmics: clues from the molecular basis of cardiac
      ryanodine receptor (RyR2) Ca2+-release channel dysfunction.
AB  - Sudden cardiac death (SCD) remains a major cause of mortality, and despite our
      knowledge of the causative genetic, molecular and biochemical cellular mechanisms
      involved, effective therapeutic strategies are lacking. Perturbations in cardiac
      Ca2+ handling promote arrhythmias and there is enormous interest in developing
      new anti-arrhythmics aimed at correcting Ca2+ release dysfunction. In particular,
      abnormal Ca2+ release arising as a result of acquired or genetic defects in
      cardiac ryanodine receptors (RyR2) has emerged as an important arrhythmogenic
      trigger in heart failure, and in a devastating genetic arrhythmia syndrome termed
      catecholaminergic polymorphic ventricular tachycardia (CPVT). Here, we evaluate
      how experimental insights into RyR2 structure-function are unravelling the
      precise molecular basis of channel dysfunction and are advancing the development
      of new therapeutic strategies. We also discuss the functional role of RyR2 in the
      context of the exquisite synergism existing between numerous cellular components
      involved in cardiac Ca2+ signalling, and how these complex interactions may be
      used to design new anti-arrhythmic approaches that target multiple facets of RyR2
      regulation.

PMID- 18045170
TI  - Functional domains of aquaporin-1: keys to physiology, and targets for drug
      discovery.
AB  - Aquaporins (AQPs) are expressed in physiologically essential tissues and organs
      in which edema and fluid imbalances are of major concern. Potential roles in
      brain water homeostasis and edema, angiogenesis, cell migration, development,
      neuropathological diseases, and cancer suggest that this family of membrane
      proteins is an attractive set of novel drug targets. A problem in pursuing
      therapeutic and basic research strategies for dissecting contributions of AQPs to
      cell and tissue functions is that little is known regarding the pharmacology of
      AQP channels; currently defined agents such as tetraethylammonium and phloretin
      as blockers for aquaporins suffer from a lack of specificity and potency.
      Subtypes of AQPs modulated by signaling pathways could enable discrete localized
      control of fluid homeostasis, volume and morphology in cells and intracellular
      organelles, and might be found to participate in many different aspects of
      physiology, such as the control of paracellular permeability, process extension,
      growth, migration, and other responses involving changes in cell shape or surface
      to volume ratios. Recognizing that AQP1 is a water channel and, under permissive
      conditions, also a cGMP-gated cation channel, evidence in various tissues for a
      coupling of the cGMP signaling cascade to a physiological outcome that might
      involve AQP1 dual ion-and-water channel functions is of interest. Groundbreaking
      advances in defining aquaporin gating mechanisms suggest conformational changes
      are important elements in regulation and gating across classes of aquaporins.
      With a rapidly expanding knowledge of aquaporin structure and functional
      regulation, new avenues for manipulation of aquaporin channels are likely to be
      discovered. In parallel, a discovery for novel compounds with specificity and
      potency for aquaporins is a compelling goal. The need for pharmacological agents
      to dissect the roles of aquaporins in physiological and pathological processes is
      a clear call for further research in the field.

PMID- 18045171
TI  - Involvement of potassium and chloride channels and other transporters in volume
      regulation by spermatozoa.
AB  - Spermatozoa produced in the testis undergo maturation in the epididymis which
      secretes an osmolyte-rich fluid that bathes the sperm cells. These cells need to
      maintain their volume after ejaculation when they first encounter hypo-osmolal
      environments of accessory gland fluids and later within the female tract. If they
      do not, they experience swelling that is manifested in flagellar angulation that
      prevents their passage through cervical mucus or the uterotubal junction and they
      never reach the oocytes. This is a cause of male infertility in domestic species
      and certain infertile transgenic mice in which flagellar angulation has been
      shown to indicate cell swelling as a consequence of reduced epididymal provision
      of osmolytes. The reduced volume regulating ability of spermatozoa from
      subfertile boars and bulls has prompted study of volume regulation of spermatozoa
      as a possible cause of human male infertility. Understanding this process may
      make its manipulation possible and could suggest better sperm handling and
      storage techniques and thus provide therapy for infertile patients. On the other
      hand, volume regulation is a potential target for contraception if mimicking the
      conditions expressed by the "sterile studs" were possible. The evidence for the
      presence of ion channels probably responsible for regulatory volume decreases in
      spermatozoa is reviewed here that implicate voltage-gated potassium channels
      (especially Kv1.5 (KCNA5), minK (KCNE1) and TASK2 (KCNK5)) and the chloride
      channels CLCN3 and CLNS1A. The involvement of ion co-transporters in volume
      regulation of spermatozoa is also discussed.

PMID- 18045172
TI  - M2 protein-a proton channel of influenza A virus.
AB  - Recent outbreaks of highly pathogenic avian influenza A virus infections (H5 and
      H7 subtypes) in poultry and humans have raised concerns that a new influenza
      pandemic will occur in near future. Currently, four antivirals have proven
      efficacy in the treatment and prophylaxis of influenza A infections: two M2
      inhibitors (amantadine and rimantadine) and two neuraminidase inhibitors
      (zanamivir and oseltamivir). Early treatment with antivirals reduces the duration
      of symptoms and the time to recovery by one to two days. However, when antivirals
      are used for the treatment the antiviral resistance develops rapidly, limiting
      their use. There is an urgent need for research on newer antiviral agents and
      "universal" vaccine against influenza virus. The M2 protein from the influenza A
      virus forms a proton channel in the virion and is essential for infection. As a
      relatively conserved protein, the M2 protein seems to be a suitable candidate for
      development of a new generation of vaccine or antiviral agents. This review
      describes the role of the M2 ion channel in virus replication and the structure
      function relationship of the channel.

PMID- 18045173
TI  - Purinergic (P2) receptor control of lower genitourinary tract function and new
      avenues for drug action: an overview.
AB  - Micturition, penile erection, contraction of prostatic smooth muscle, peristalsis
      of the male excurrent duct system and lumbosacral spinal cord neurotransmission
      all require adenosine 5'-triphosphate (ATP) activity and this likely involves
      purinergic (P2) receptors. P2 receptors are categorized as either ligand-gated
      ionotropic P2X or metabotropic G-protein-coupled P2Y subtypes. In the urinary
      bladder, purinergic receptor mechanisms are involved in both motor and sensory
      function. In the prostate, P2X1-receptors, which mediate contraction, are present
      in the fibromuscular stroma while G protein-coupled P2Y purinoceptors have a wide
      range of actions in prostate cancer. In the excretory ducts of the testis (ductus
      epididymidis, vas deferens and its associated seminal vesicles), heavy
      immunostaining for P2X1 and P2X2 subtypes is detected in the membranes of smooth
      muscle, suggesting their role in sperm transport and ejaculation. In the penis,
      intense P2X1 and weak P2X2 immunoreactivity are observed in smooth muscle of
      blood vessels and the corpus cavernosum, implying their participation in
      detumescence. Human corporal cavernosum stimulation induces relaxation of P2Y
      purinoceptors. Targeting of extracellular or intracellular P2X and/or P2Y
      receptor signaling pathways holds promise in affecting the lower genitourinary
      tract system. Our advancing knowledge about purine agonists and their
      pharmacologic benefits in erectile, ejaculatory, urinary bladder and prostatic
      hyperplasia may service clinical problems in the near future.

PMID- 18045174
TI  - Therapeutic approaches in vascular repair induced by adult bone marrow cells and
      circulating progenitor endothelial cells.
AB  - Strong evidence indicates that bone marrow cells (BMCs) can contribute to the
      healing process of injured vascular system via CXCR4/Thymosin beta4/Integrin
      alpha4beta1/SDF-1 molecular pathways. We discuss the therapeutic approaches of
      BMCs and circulating endothelial progenitor cells (EPCs) to restore
      vascularization. Today some clinical trials employing BMCs in the treatment of
      peripheral vascular diseases have been completed with encouraging results. When
      large clinical controlled studies will be completed, the scientific community
      will evaluate this novel and promising therapeutic approach. Although some basic
      studies suggest the potential use of adult/somatic stem cell for vascular repair,
      other stringent data suggest that this potential is dependent also on growth
      factor synthesis rather than the formation of new arterial vessels. Considering
      the limitations of adult stem cells especially in elderly subjects, our point of
      view is that BMCs or exogenous BMC/EPC are candidate for adjunct cell-therapy
      applications in vascular repair.

PMID- 18045175
TI  - Novel pharmaceutical approaches for treating patients with cystic fibrosis.
AB  - Before the cloning of the CFTR gene in 1989, there were relatively few treatment
      options for the many phenotypes associated with cystic fibrosis (CF). The
      advancement of research in areas such as immunology, molecular biology and
      pharmacology have provided new insights into the mechanism and evolution of CF.
      More than 40 systematic clinical trials evaluating new therapies for CF are
      presently registered with the NIH. A great deal of effort is focused on the main
      cause of mortality: chronic and persistent lung infections. Intestinal
      malabsorption, pancreatic insufficiency, reduced bone mineral density and
      reproductive abnormalities are other manifestations of this disease that have
      been targeted by innovated treatments which are giving renewed hope to CF
      patients and their families. The following review is a summary of the novel
      pharmaceutical approaches for the treatment of cystic fibrosis aimed at improving
      both the quality and the longevity of the lives of patients afflicted with this
      devastating disease.

PMID- 18045177
TI  - Liver transplantation for hepatocellular carcinoma: current role and future
      opportunities.
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignancy of the
      liver. It represents the fifth most common cancer worldwide, and one whose
      incidence is on the rise. Liver cancer is the third most common cause of cancer
      mortality globally and thus a major health concern worldwide. Therapeutic options
      for this tumor include surgical resection, local ablative therapies, and systemic
      treatment. Liver transplantation has emerged as a highly effective treatment for
      patients with HCC, particularly in the setting of significant underlying liver
      disease. Current protocols in transplantation for this tumor utilize strict size
      criteria and staging (TNM classification) to select patients for this therapy.
      Selection criteria for liver transplantation for HCC that are accepted in the
      U.S. include: 1 tumor < 5cm, no greater than three tumor nodules, each less than
      3cm in diameter 3) no macroscopic invasion of blood vessels or lymph nodes, and
      no extra-hepatic spread of tumor. Eligibility criteria and immunosuppression
      strategies are continuing to evolve in this field. Nonetheless, in appropriately
      selected patients, liver transplantation may provide a cure for HCC with survival
      rates equal to that of liver transplantation for end-stage liver disease (ESLD)
      from other causes. Liver transplantation has been established as one of the
      principal treatment modalities for this difficult disease.

PMID- 18045178
TI  - Transcutaneous treatments of hepatocellular carcinoma in patients with cirrhosis:
      present status and future developments.
AB  - Hepatocellular carcinoma is in 90% of cases associated with cirrhosis and to
      preserve liver function while destroying the tumor is a main issue in these
      patients justifying the development of local percutaneous ablative therapies.
      Alcoholization and radiofrequency ablation are the most widely used techniques of
      percutaneous ablation. Both have in common limitations linked to the size of the
      tumor and its situation and contra indications such has advanced liver disease
      and unpaired hemostasis. Radiofrequency ablation despite specific contra
      indications such as a close vicinity of the colon has shown better results in
      term of tumor necrosis local recurrence and even survival. For tumors less than
      3cm in diameter results are comparable to those of surgical resection with a
      lesser morbidity. Due to this equivalence and the multiple contra indications of
      surgical resection in patients with cirrhosis radiofrequency ablation is becoming
      an increasingly popular technique for treating small hepatocellular carcinoma
      detected by screening.

PMID- 18045179
TI  - Molecular pathways and related target therapies in liver carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a frequent neoplasia which still misses a
      therapeutical gold standard. Recently, new acquisitions in cancerogenesis process
      evidenced the genetic and epigenetic alterations of genes involved in the
      different metabolic pathways of liver cancer suggesting that antibodies, small
      molecules, demethylating agents, etc. specifically acting against molecular
      target can be utilized alone or in combination in clinical practice. The main
      altered targets are: cell membrane receptors, in particular tyrosine kinase
      receptors, factors involved in cell signalling, specifically Wnt/beta-catenin,
      Ras/Raf/MEK/ERK and PI3K/Akt/mTOR pathways, proteins linked to cell cycle
      regulation pathway (i.e. p53, p16/INK4, cyclin/cdk complex) or in invasiveness
      (EMT, TGFbeta) and proteins involved in DNA metabolism. Genetic or epigenetic
      changes in these molecules have been used in preclinical settings and, some of
      them also in clinical trials of phase II and III. This scenario opens new avenues
      for the prevention and the treatment of HCC. In the present review the main
      metabolic pathways and molecular alterations have been described together with
      recent advances in molecular and gene therapy.

PMID- 18045180
TI  - Rationale for new drugs targeting the tissue microenvironment in patients with
      HCC.
AB  - A better knowledge of the mechanisms underlying hepatocellular carcinoma (HCC)
      growth and spread is essential to improve the available treatment options. So
      far, the only therapies available for HCC are mainly based on tumor-destructive
      approaches, whereas no therapies are available to consolidate these invasive
      therapies or to cure the tumor. The fact that HCC develops on cirrhotic liver
      strongly limits the use of common anti-cancer drugs, but the need to find new
      therapies is strongly felt by clinicians. A large body of evidence suggests that
      the tissue microenvironment represents a potential target for therapies.
      Consistently, biological therapies such as inhibitors of the epithelial growth
      factor receptor (EGFR), are currently under investigation. Unfortunately, there
      is a discrepancy between the very promising experimental data and the results
      obtained in patients, although limited sample sizes and advanced stage of the
      disease could be important factors hampering a reliable judgment of the efficacy
      of such drugs. Nevertheless, a better identification of the molecular pathways
      involved in drug effectiveness as well as in HCC tumor progression indicates that
      the tissue microenvironment likely harbors the solution to the problem. In this
      review the role and the rationale of using biological drugs to target the
      microenvironment is discussed, taking into consideration new experimental
      advances in the field.

PMID- 18045181
TI  - The development of targeted therapies for hepatocellular cancer.
AB  - Present treatment options for hepatocellular cancer (HCC) are limited to those
      individuals with good liver function and early stage disease. Unfortunately this
      includes only a minority of patients, few of which are actually cured of their
      cancer. Over the last 15-20 years biotechnology has made a very significant
      impact on medical research, to the extent that we know very much more about the
      regulation of normal cell growth and death, as well as the mechanisms underlying
      its disruption in disease processes. This knowledge has and is being rapidly
      exploited by academic and pharmaceutical organisations, often in collaboration.
      The result is the development, testing and steady introduction of therapies that
      target specific abnormalities in cancer cells. Although the safety and
      effectiveness of the majority of these agents has yet to be established in
      cirrhotic patients with HCC, we are hopeful that we will shortly see an increase
      in effective treatment options available for clinical use this disease. This
      review focuses on aberrant cancer proteins and pathways relevant to HCC, as well
      as the novel therapies or strategies targeting them, that are currently in the
      development or testing stages.

PMID- 18045182
TI  - Tyrosine kinase inhibitors: a potential approach to the treatment of
      hepatocellular carcinoma.
AB  - The increasing number of patients with hepatocellular carcinoma (HCC) and the
      highly unfavourable prognosis of the disease are two important reasons why more
      effort needs to be devoted to investigating other therapies able to block or
      reduce tumor progression and cancer metastasis. The underlying cirrhosis on which
      HCC develops limits the use of common chemotherapies, mainly because of their
      toxicity. Recently, great attention has been paid to a family of molecules that
      inhibits the tyrosine kinase (TK) receptors, because of their relevant role in
      activating intracellular pathways responsible for several biological activities
      of the HCC cells. In particular, proliferation, invasion, survival, apoptosis,
      are regulated by Erk1/2 and Akt pathways, that can be considered for this reason
      as potential therapeutic targets. Therefore, the idea is to fight HCC by blocking
      the molecular mechanisms exploited by the cancer to develop and to metastasize.
      The epithelial growth factor and the vascular endothelial growth factor receptors
      (EGFR and VEGFR, respectively) have been identified as the major targets for
      these new therapies. In this review the biological role of both growth factors in
      HCC will be discussed, together with the use of anti-EGFR and anti-VEGFR. The
      preliminary results obtained in vitro or in "in vivo" experimental models have
      been very promising, whereas the few studies conducted in patients have been not
      comparably satisfactory. This could be because of the limited number of patients
      and of their advanced stage of HCC, nevertheless the possibilities of using this
      family of drugs should be further explored, together with aspects contributing to
      a better understanding of the molecular mechanisms driving HCC progression.

PMID- 18045183
TI  - Cyclooxygenase-2 (COX-2)--a therapeutic target in liver cancer?
AB  - Targeting COX-2, a key-enzyme of the prostaglandin metabolism, for the treatment
      of cancer has been in the focus of researchers for about a decade. However, only
      recently has this topic been related to hepatocellular carcinoma (HCC). HCC is
      one of the most common cancers and a growing health problem worldwide. At
      present, only few promising treatment options are available, accentuating the
      urgent need for novel therapeutic approaches. Since the first report of COX-2
      overexpression in HCC, several findings support the notion that selective COX-2
      inhibition proves to be beneficial in this malignancy. This review focuses on
      recent discoveries regarding the pro-tumorigenic potential of COX-2 in HCC and
      the functional effects of COX-2 inhibition on molecular mechanisms of this
      malignancy. Of clinical interest, promising data from in vivo experiments and
      case studies suggest a beneficial effect of COX-2 inhibitors for HCC- therapy.
      Detailed analysis of COX-2- activated pathways and related mechanisms may enable
      the evaluation and design of even more specific and combinatorial treatment
      approaches in the future.

PMID- 18045185
TI  - New developments in MALDI imaging for pathology proteomic studies.
AB  - With new emerging mass spectrometry technologies, it can now be demonstrated that
      direct tissue analysis is feasible using matrix-assisted laser
      desorption/ionization (MALDI) sources. A major advantage of direct MALDI analysis
      is to avoid time-consuming extraction, purification or separation steps, which
      have the potential for producing artifacts. Direct MALDI analysis of tissue
      sections enables the acquisition of cellular expression profiles while
      maintaining the cellular and molecular integrity. With automation and the ability
      to reconstruct complex spectral data using imaging software, it is now possible
      to produce multiplex imaging maps of selected bio-molecules within tissue
      sections. Thus, direct MALDI spectral data obtained from tissue sections can be
      converted into imaging maps, a method now known as MALDI-imaging. MALDI-imaging
      combines the power of mass spectrometry, namely exquisite sensitivity and
      unequivocal structural information, within an intact and unaltered morphological
      context. Critical improvements to increase image resolution are presented in this
      manuscript e.g., solvent treatment, new solid ionic matrices, gold sputtering,
      nickel support or laser focalization. One of the most important developments is
      the ability to carry out either direct MALDI analysis or MALDI imaging on
      paraffin tissue sections, thus opening the path to an archival "gold-mine" of
      existing pathology samples to proteomic analysis. These developments provide new
      avenues for biomarker hunting and diagnostic follow-up in the clinical setting.
      Further developments in MALDI-imaging of specific targets provide an added
      dimension, as validated disease-marker-gene RNA transcripts can be analyzed along
      with their translation by targeting their specific protein products or
      metabolites. Disease/health states will thus be closely molecularly monitored at
      protein and nucleic acids levels, with a single technique. Taken together, MALDI
      imaging will become a key tool for pathology proteomic studies.

PMID- 18045186
TI  - Mass spectrometric imaging of the nervous system.
AB  - Mass spectrometric imaging (MSI) integrates multiple fields of analytical and
      biomedical research with the goal of generating chemical maps that present the
      identity and location of the elements, molecules, and molecular complexes that
      comprise biological structures. Rapid advances in the development of MSI, which
      include a broad range of sampling and mass spectrometry strategies, allow the
      increasingly information-rich creation of chemical images of structurally complex
      tissues, individual cells, and even single chromosomes. Here we describe a
      variety of MSI techniques available to investigate the nervous system, with
      particular focus on the capability of MSI to examine both normal and diseased
      brain function. An important investigative tool, MSI offers tremendous potential
      in fundamental studies of brain chemistry, localization of pharmaceutical
      compounds, and the discovery of biomarkers for different neuropathologies.

PMID- 18045187
TI  - Recent advances in biological tissue imaging with Time-of-flight Secondary Ion
      Mass Spectrometry: polyatomic ion sources, sample preparation, and applications.
AB  - Recent technological and methodological improvements have greatly enhanced the
      sensitivity of the Time-of-flight Secondary Ion Mass Spectrometry (TOF-SIMS),
      thus making this technique now very attractive in the field of molecular imaging
      of biological samples such as tissue sections or cells. This paper reviews the
      most recent advances in this field. After a short reminder of the basic physics
      involved, the instruments are described, as well as the primary ion sources,
      including the different cluster ion sources. The sample preparation methods are
      also described and compared, such as the matrix coating and the metal coating.
      The capabilities of the technique are finally illustrated with the most recent
      applications published in the last years.

PMID- 18045188
TI  - A snapshot of tissue glycerolipids.
AB  - The lipid membrane is the portal to the cell and its first line of defense
      against the outside world. Its plasticity, diversity and powers of accommodation
      in a myriad of environments, mirrored by the varied make up of the cells it
      protects, are unparalleled. Glycerophospholipids are one of its major components.
      In cell membranes the extracellular layer is mainly made up of positively charged
      glycolipids, while the intracellular one's main components are negatively
      charged. Advances in mass spectrometry have allowed the direct probing of
      tissues, and thus a direct approach to probing membranes make up was developed.
      Until recently most studies have focused on proteins. An overview of the use of
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS) for the direct analysis of phospholipids in various tissue is
      presented. Molecular ions corresponding to phosphatidylcholines, sphingomyelin,
      phosphatidylethanolamines, phosphatidylserines, phosphatidylinositols and
      sulfatides were mapped.

PMID- 18045190
TI  - Rational combination of targeted therapies as a strategy to overcome the
      mechanisms of resistance to inhibitors of EGFR signaling.
AB  - The epidermal growth factor receptor (EGFR) has been widely used as a target for
      novel anticancer agents, such as blocking antibodies and small molecular weight
      tyrosine kinase compounds. In spite of recent advances in cancer cell biology,
      leading to the introduction of clinically active new drugs, such as cetuximab,
      panitumumab and erlotinib, unfortunately disease control remains unsuccessful due
      to the presence of constitutive resistance to EGFR inhibitors in most patients
      and the development of acquired resistance in the responders. A large number of
      molecular abnormalities in tumor cells seem to partly contribute to their
      resistance to anti-EGFR therapy: increased angiogenesis, constitutive activation
      of downstream mediators, overexpression of other tyrosine kinase receptors.
      Moreover, some mutations in the EGFR receptor kinase domain seem to play a
      crucial role in determining the sensitivity of cancer cells to specific
      inhibitors by altering the conformation of the receptor and its activity. The
      development of rational combinations of anticancer agents and EGFR inhibitors,
      able to exert synergistic cytotoxic interactions, has been widely accepted and
      used in both preclinical and clinical studies. Although the failure of large
      clinical trial based on empirical combination of anti-EGFR and classic
      chemotherapeutic agents, several preclinical data seems to support the hypothesis
      that combining EGFR inhibitors and other novel agents could efficiently inhibit
      tumor growth and overcome intrinsic resistance to a single-agent based therapy.
      This review focuses on the role of complementary signalling pathways in the
      development of resistance to EGFR targeting agents and the rationale to combine
      novel inhibitors as anticancer therapy.

PMID- 18045191
TI  - Thioredoxin and thioredoxin reductase as redox-sensitive molecular targets for
      cancer therapy.
AB  - Tumor cell proliferation, de-differentiation, and progression depend on a complex
      combination of altered intracellular processes including cell cycle regulation,
      excessive growth factor pathway activation, and decreased apoptosis. Metabolites
      from these processes result in significant cellular oxidative stress that must be
      buffered to prevent permanent cell damage and cell death. Tumor cells depend on a
      complex set of respiratory pathways to generate the necessary energy as well as
      redox-sensitive pro-survival signaling pathways and factors to cope with and
      defend against the detrimental effects of oxidative stress. It has been
      hypothesized that redox-sensitive signaling factors such as thioredoxin reductase
      1 (TR) and thioredoxin (TRX) may represent central pro-survival factors that
      would allow tumor cells to evade the damaging and potentially cytotoxic effects
      of endogenous and exogenous agents that induce oxidative stress. The overarching
      theme of this review is an extension of the hypothesis that tumor cells use these
      redox sensitive pro-survival signaling pathways/factors, which are up-regulated
      due to increased tumor cell respiration, to evade the cytotoxic effects of
      anticancer agents. These observations suggest that redox-sensitive signaling
      factors may be potential novel molecular targets for drug discovery.

PMID- 18045192
TI  - Valproic acid as anti-cancer drug.
AB  - The short chain fatty acid valproic acid (VPA, 2-propylpetanoic acid) is approved
      for the treatment of epilepsia, bipolar disorders and migraine and clinically
      used for schizophrenia. In 1999, the first clinical anti-cancer trial using VPA
      was initiated. Currently, VPA is examined in numerous clinical trials for
      different leukaemias and solid tumour entities. In addition to clinical
      assessment, the experimental examination of VPA as anti-cancer drug is ongoing
      and many questions remain unanswered. Although other mechanisms may also
      contribute to VPA-induced anti-cancer effects, inhibition of histone deacetylases
      appears to play a central role. This review focuses on recent developments
      regarding the anti-cancer activity of VPA.

PMID- 18045193
TI  - Cancer control by phytochemicals.
AB  - Chemoprevention is one of the most important strategy in the field of cancer
      control. Molecular mechanism-based cancer chemoprevention by phytochemicals seems
      to be very attractive method. In this review, possible molecular targets for
      cancer prevention are overviewed, and some examples of cancer preventive
      phytochemicals, such as carotenoids, are presented.

PMID- 18045194
TI  - Anticancer drugs designed by mother nature: ancient drugs but modern targets.
AB  - Nuclear factor-kappaBeta (NF-kappaBeta) is a transcription factor that is
      activated in response to various inflammatory stimuli such as cytokines, growth
      factors, hormones, mitogens, carcinogens, chemotherapeutic agents, viral
      products, eukaryotic parasites, endotoxin, fatty acids, metals, radiation,
      hypoxia, and psychological, physical, oxidative, and chemical stresses. In
      addition, constitutively active NF-kappaBeta is frequently encountered in a wide
      variety of tumors. Furthermore, NF-kappaBeta activation has been shown to
      regulate the expression of over 400 genes involved in cellular transformation,
      proliferation, inflammation, viral replication, antiapoptosis, angiogenesis,
      invasion and metastasis, oxidative stress, and osteoclastogenesis. Therefore,
      because of the critical role NF-kappaBeta plays in the pathogenesis of cancer,
      specific inhibitors of this factor are being sought. Agents that prevent cancer
      or inflammation have been found to suppress NF-kappaBeta activation. Numerous
      reports indicate that ancient plants and their components are potent as NF-kappaB
      inibitors. However, ancient medicine such as traditional Chinese medicine, Kampo,
      Ayurveda requires rediscovery in light of our current knowledge of allopathic
      (modern) medicine for the therapeutic and preventive purpose. In this review, we
      present evidence that numerous agents identified from fruits and vegetables can
      interfere with NF-kappaBeta pathway. The structure of drugs and their
      relationship with NF-kappaBeta inhibitory activity is discussed.

PMID- 18045195
TI  - Novel marine-derived anti-cancer agents.
AB  - There is an immense diversity of marine plants and animals from which an
      estimated 14,000 pharmacologically active compounds have been isolated. However,
      in terms of clinically useful anti-cancer agents, the oceans remain as a largely
      untapped resource. Indeed, there are currently only two compounds used in the
      clinic that are derived from marine sources. These are cytarabine, which is a
      deoxycitidine analogue and aplidine, which has both growth inhibitory and anti
      angiogenic effects. This situation is likely to change rather dramatically in the
      near future, as attention has focused on the vast diversity of available agents
      from marine organisms. The increased pace of activity in this area has resulted
      in a several clinical trials of promising compounds with the probability that
      these will be followed by other drugs currently under preclinical development.

PMID- 18045196
TI  - Aplidine: a paradigm of how to handle the activity and toxicity of a novel marine
      anticancer poison.
AB  - The marine ecosystem that has contributed to the discovery of cytarabine and its
      fluorinated derivative gemcitabine is now considered the most productive toll to
      acquire new natural derived anticancer entities. Few marine anticancer agents
      have entered clinical development, including bryostatin-1, dolastatin 10,
      LU103793, ET-743, kahalalide F, didemnin B and aplidine. The marine plitidepsin
      aplidine derived from the mediterranean tunicate Aplidium albicans is a
      synthetically produced anticancer agent that is structurally related to
      didemnins. Aplidine's mechanism of action involves several pathways, including
      cell cycle arrest, inhibition of protein synthesis and antiangiogenic activity.
      Phase I studies have been reported for a number of several schedules including 1
      hour, 3-hour and 24-hour infusion. Evidences of antitumor activity and clinical
      benefit of aplidine in several tumor types were noted across phase I trials,
      particularly in advanced medullar thyroid carcinoma. Phase II studies are
      underway. Within the entire phase I program, dose-limiting toxicities of aplidine
      were neuromuscular toxicity, asthenia, skin toxicity, and diarrhea.
      Interestingly, no hematological toxicity was observed. Aplidine displayed a very
      peculiar delayed neuromuscular toxicity that was found to be closely related to
      the symptoms described in the adult form of carnitine palmitoyl transferase
      deficiency type 2, which is a genetic disease treated with L-carnitine.
      Consistently, concomitant administration of L-carnitine allowed to improve
      aplidine-induce neuromuscular toxicity. In summary, aplidine is a novel marine
      anticancer agent with a very particular delayed neuromuscular toxicity that
      requires careful follow-up with promising antitumor activity.

PMID- 18045197
TI  - Connecting a tumor to the environment.
AB  - Tumor cells are not only susceptible to signals from the environment, but they
      likewise release signal substances. It is well known that tumor cells secrete
      angiogenic factors--most prominently the vascular endothelial growth factor-
      which initiate the vascularization of the tumor for its nourishment. This process
      has been termed neoangiogenesis. Besides this, two further processes have
      recently been discovered that facilitate the interaction of the tumor with the
      lymphatic system and the nervous system, named lymphangiogenesis and
      neoneurogenesis. These three "geneses" have a cognate, in part common regulation
      and conjointly promote metastasis development. Neoangiogenesis and
      lymphangiogenesis provide the structures for the two routes of tumor cell
      dissemination, i.e. either hematogenous or lymphatic. Neoneurogenesis
      accomplishes the innervation of the tumor by the ingrowth of nerve endings into
      the tumor and alternatively or additionally by the protection of existing nerve
      cells from destruction. These tumor-innervating nerve cells may release
      neurotransmitters which are proliferative or promigratory signals for the tumor
      cells. Furthermore, nerve fibers are used as routes for tumor cell dissemination,
      too, which is known as perineural invasion.

PMID- 18045198
TI  - Structural factors influencing potency of currently used acetylcholinesterase
      reactivators for treatment of cyclosarin intoxications.
AB  - Cyclosarin is one member of nerve agent family. Recent treatment of intoxications
      by organophosphorus compounds, such as nerve agents or pesticides, consists of
      rapid administration of anticholinergics and AChE reactivators. Owing to the
      threat of terroristic use of these compounds during last years, improvement of
      antidotal therapy still continues. As the part of the development of new
      antidotes, many new AChE reactivators were synthesized and currently some of them
      are under consideration for introducing them to the medical practice. Their
      biological activity depends, as in the case of other drugs, on their chemical
      structure, which affects their pharmacokinetics (adsorption, distribution,
      metabolism and excretion) and pharmacodynamics. In this review, we would like to
      discuss relationship between structure of currently available AChE reactivators
      and their potency to reactivate cyclosarin-inhibited AChE. All outlined
      structural factors presented in this work should be helpful for the design of new
      generation of reactivators of cyclosarin-inhibited AChE.

PMID- 18045199
TI  - Synthesis and biological evaluation of 2-amino-3-(3', 4', 5'-trimethoxy
      phenylsulfonyl)-5-aryl thiophenes as a new class of antitubulin agents.
AB  - Bioisosterism represents one approach used by the medicinal chemist for the
      rational modification of lead compounds into safer and more clinically effective
      agents. Bioisosteres are substituents or groups that have chemical or physical
      similarities and that produce broadly similar biological effects. The sulfone
      moiety is recognized as a nonclassical bioisostere for replacement of the
      carbonyl group. When sulfonyl derivatives 5a-e were compared with carbonyl
      compounds 4a-e, the sulfone substitution dramatically decreased the
      antiproliferative activity of the series.

PMID- 18045200
TI  - Design, synthesis and biological evaluation of a series of thioamides as non
      nucleoside reverse transcriptase inhibitors.
AB  - A series of thioamides were designed as bio-isosteres to the non-nucleoside
      reverse transcriptase inhibitor trovirdine by replacement of the thiourea NH
      groups with methylene groups. Eight thioamides were synthesized and in vitro
      tested for inhibitory effects on the activity of HIV-1 reverse transcriptase wild
      and mutant types. Three of the 8-thioamides exhibited enzyme inhibitory
      activities with IC(50) values below 100 microM. While compound (2) exhibited
      activity against the mutant strain L100I with IC(50) of 70.1 microM, compound (4)
      showed activity against the mutant strain K103N with IC(50) of 92.7 microM, and
      compound (8) with activity against the wild type enzyme with IC(50) of 8.9
      microM. Each of the three thioamides could serve as a lead compound for further
      activity optimization.

PMID- 18045201
TI  - Synthesis and anti-picornaviridae in vitro activity of a new class of helicase
      inhibitors the N,N'-bis[4-(1H(2H)-benzotriazol-1(2)-yl)phenyl]
      alkyldicarboxamides.
AB  - A series N,N'-bis[4-(1H(2H)-benzotriazol-1(2)-yl)phenyl]alkyldicarboxamides (3a-f
      and 5a-j) were prepared starting from their already known (1a-d) and (4a-c) or
      new (4d) amine parents. Because of the antiviral activity of several N-[4-(1H(2H)
      benzotriazol-1(2)-yl)phenyl]alkylcarboxamides previously reported, title
      compounds were evaluated in vitro for cytotoxicity and antiviral activity against
      viruses representative of Picornaviridae, [i.e. Enterovirus Coxsackie B2 (CVB-2)
      and Polio (Sb-1)] and of two of the three genera of the Flaviviridae [Bovine
      Viral Diarrhea Virus (BVDV) and Yellow Fever Virus (YFV)]. Furthermore, because
      of the in silico activity against the RNA-dependent RNA-helicase of Polio 1
      previously reported, title compounds were evaluated against the 3D model of the
      Sb-1 helicase and against the 2D model of the CVB-2 helicase. As a reference we
      used the antiviral and in silico activities of an imidazo counterpart of the
      title compounds, N,N'-bis[4-(2-benzimidazolyl)phenyl]alkyldicarboxamides (III)
      that other authors reported to be able to inhibit the corresponding enzyme of
      Hepatitis C Virus (HCV). In cell-based antiviral assays, N,N'-bis[4-(1H
      benzotriazol-1-yl)phenyl]alkyldicarboxamides (3a-f) resulted completely inactive
      whereas the bis-5,6-dimethyl-benzotriazol-2-yl derivatives (5d-f) exhibited good
      activity against the Enteroviruses, (EC(50)s ranged between 7 and 11 microM
      against CVB-2 and 19-52 against Sb-1). Interestingly, bis-5,6-dichloro
      benzotriazol-2-yl derivatives (5h-j) showed very selective activity against CVB-2
      (EC(50)s = 4-11 microM) whereas they resulted completely inactive against all the
      other viruses screened. In general, all title compounds showed a good
      cytotoxicity profile in MT-4 cells. Molecular modeling investigations showed that
      active compounds may interact with the binding site of the Sb-1 helicase and that
      their free binding energy values are in agreement with their EC(50)s values.

PMID- 18045202
TI  - Design, synthesis and pharmacological evaluation of HIV-1 reverse transcriptase
      inhibition of new indolin-2-ones.
AB  - The design, synthesis and anti HIV-1 replication inhibition of 3
      (cyclopropylethynyl)-3-hydroxy-indolin-2-ones, analogues of efavirenz
      (Sustivatrade mark), are described. Different substituted isatins were used to
      generate final products that contain pharmacophoric features for RT inhibition,
      such as the oxoindole and cyclopropylethynyl groups. The suitability of the
      indolin-2-one ring in the planned compounds in replacement to the benzoxazinone
      ring of efavirenz was proven, since compound 15 presented a greater activity than
      efavirenz against HIV-1 replication and was not significantly cytotoxic.

PMID- 18045203
TI  - The preparation and human muscarinic receptor profiling of oxybutynin and N
      desethyloxybutynin enantiomers.
AB  - Oxybutynin (1) is a non-selective muscarinic receptor antagonist that is used
      clinically for the treatment of urinary incontinence. The major metabolite of
      oxybutynin in humans is desethyloxybutynin (2). We have prepared the enantiomers
      of 1 and 2 and evaluated their ability to displace N-CT(3)-scopolamine chloride
      ((3)H-NMS) binding on human cloned muscarinic m1-5 receptors. Compounds 1 and 2
      potently displaced (3)H-NMS binding at m1, m3 and m4 receptors, but were less
      potent at the m2 and m5 subtypes. However, metabolite 2 was more potent than the
      parent compound 1 in the binding assay. In general the R enantiomers were more
      potent than their respective S enantiomers. Therefore, we suggest that the
      cholinergic side effects associated with 2 may be due to its greater apparent
      potency with m1 and m3 receptors, especially of its R-enantiomer, when compared
      with parent drug 1.

PMID- 18045204
TI  - A salicylic acid-based analogue discovered from virtual screening as a potent
      inhibitor of human 20alpha-hydroxysteroid dehydrogenase.
AB  - 20alpha-hydroxysteroid dehydrogenase (AKR1C1) plays a key role in the metabolism
      of progesterone and other steroid hormones, thereby regulating their action at
      the pre-receptor level. AKR1C1 is implicated in neurological and psychiatric
      conditions such as catamenial epilepsy and depressive disorders. Increased
      activity of AKR1C1 is associated with termination of pregnancy and the
      development of breast cancer, endometriosis and endometrial cancer. Inhibition of
      the undesired activity of AKR1C1 will help reduce risks of premature birth,
      neurological disorders and the development of cancer. In order to identify
      potential leads for new inhibitors of AKR1C1 we adopted a virtual screening-based
      approach using the automated DOCK program. Approximately 250,000 compounds from
      the NCI database were screened for potential ligands based on their chemical
      complementarity and steric fit within the active site of AKR1C1. Kinetic analysis
      revealed 3,5-diiodosalicylic acid, an analogue of salicylic acid, as a potent
      competitive inhibitor with respect to the substrate 5beta-pregnane-3alpha,20alpha
      diol with a K(i) of 9 nM. Aspirin, which is a well known salicylic acid-based
      drug, was also found to inhibit AKR1C1 activity. This is the first report to show
      aspirin (IC(50)=21 microM) and its metabolite salicylic acid (IC(50)=7.8 microM)
      as inhibitors of AKR1C1.

PMID- 18045205
TI  - Synthesis of 1,2,4-triazole derivatives: binding properties on endothelin
      receptors.
AB  - In the present study we describe the synthesis of a new series of 1,2,4
      triazoles: [3-(arylmethyl)thio-5-aryl-4H-[1,2,4]triazol-4-yl]acetic acids 5a-g,
      [5-(arylmethyl)thio-3-aryl-1H-[1,2,4]triazol-1-yl]acetic acids 8a-d, and [3-(aryl
      methyl)thio-5-aryl-1H-[1,2,4]triazol-1-yl] acetic acids 9a-d. These compounds
      were tested in binding assays to evaluate their ability as ligands for human
      ET(A) and ET(B) receptors stably expressed in CHO cells; some of the tested
      compounds showed affinity in the micromolar range.

PMID- 18045206
TI  - Design and synthesis of new N-OMe fluoro-indole melatoninergics.
AB  - The synthesis of a series of new N-OMe fluoro-indoles with melatoninergic
      activity in the Xenopus melanophore assay is described. All of the 4-F
      substituted compounds, 22a-e and 25a,b, were antagonists on the clonal Xenopus
      melanophore line. Conversely, the 5-F substituted analogs (15a-e) did not share
      the same pharmacological profile, as two of them, compounds 15d (R=c-C(3)H(5))
      and 15e (R=c-C(4)H(7)), exhibited a weak agonistic and partial agonistic
      activity, respectively, whilst the other three (15a-c) were all agonists. It
      seems that in this case the nature of the response (agonist or antagonist
      activity) is solely dependent on the shape of the R group.

PMID- 18045207
TI  - New steroidal anti-inflammatory antedrugs: 21-thioalkylether derivatives of
      methyl 16-prednisolone carboxylates.
AB  - Antedrug approach of the corticosteroids has been described as a fundamentally
      sound approach for the development of safer anti-inflammatory steroids devoid of
      systemic side effects. In our continued efforts under the antedrug paradigm, we
      have recently extended this effort to synthesize the 21-thioalkylether
      derivatives of methyl 16-prednisolonecarboxylates. The 21-mesylate of the methyl
      16-perdnisolonecarboxylates and 9-fluoro-17-dehydro methyl 16
      prednisolonecarboxylate were reacted with Na-thioalkoxides to furnish the desired
      thioalkylethers in 60-75% yields. These newly synthesized thioalkylether steroid
      series were tested for their in vitro metabolism and corticosteroid receptor
      binding affinity. They were metabolized in predictable manner to inactive 16
      carboxylic acids. All the newly synthesized antedrugs showed lowered
      glucocorticoid receptor binding affinity than prednisolone indicating that the
      replacement of the 21-OH function with thioalkylether of the 16-prednisolone
      carboxylate esters decreases their receptor binding affinity.

PMID- 18045208
TI  - Computational approach to drug design for oxazolidinones as antibacterial agents.
AB  - A three dimensional Quantitative Structure Activity Relationship (3D-QSAR) model
      for a series of (S)-3-Aryl-5-substituted oxazolidinones was developed to gain
      insights into the design for potential new antibacterial agents. It was found
      that the Comparative Molecular Field Analysis (CoMFA) method yielded good results
      while the Comparative Molecular Similarity Indices Analysis (CoMSIA) was less
      satisfactory. The CoMFA method yielded a cross-validated correlation coefficient
      q(2) = 0.681, non-cross-validated R(2) = 0.991, SE (Standard Error ) = 0.054, and
      the value of statistical significance measure F = 266.98. The relative steric and
      electrostatic contributions are 0.542 and 0.458, respectively. These results
      indicate that the model possesses a high predictivity. Guided by this model,
      three new compounds were synthesized. All these compounds exhibit inhibitory
      activity; two of them were shown having high activity (MIC = 1.0 microg/ml). The
      activity observed by experiments was in good agreement with the theoretical one.
      It is anticipated that the present model would be of value in facilitating design
      of new potent antibacterial agents.

PMID- 18045209
TI  - Synthesis of opioidmimetics, 3-[H-Dmt-NH(CH(2))(m)]-6-[H-Dmt-NH(CH(2))(n)]-2(1H)
      pyrazinones, and studies on structure-activity relationships.
AB  - Opioidmimetics containing 3-[H-Dmt-NH-(CH(2))(m)]-6-[H-Dmt-NH-(CH(2))(n)]-2(1H)
      pyrazinone symmetric (m = n, 1-4) (1 - 4) and asymmetric (m, n = 1 - 4) aliphatic
      chains (5 - 16) were synthesized using dipeptidyl chloromethylketone
      intermediates. They had high mu-affinity (K(i)mu = 0.021 - 2.94 nM), delta
      affinity (K(i)delta = 1.06 - 152.6 nM), and mu selectivity (K(i)delta/K(i)mu = 14
      - 3,126). The opioidmimetics (1 - 16) exhibited mu agonism in proportion to their
      mu-receptor affinity. delta-Agonism was essentially lacking in the compounds
      except (4) and (16), and (1) and (2) indicated weak delta antagonism (pA(2) =
      6.47 and 6.56, respectively). The data verify that a specific length of aliphatic
      linker is required between the Dmt pharmacophore and the pyrazinone ring to
      produce unique mu-opioid receptor ligands.

PMID- 18045210
TI  - In vitro binding receptors study by Valeriana adscendens, Iresine herbstii and
      Brugmansia arborea extracts.
AB  - In this work we examined the affinity and the selectivity of V. adscendens,
      Iresine herbstii Hook. (Amaranthaceae) and Brugmansia arborea (L.) Lagerheim
      (Solanaceae) towards 5-HT(1A), 5-HT(2A), 5-HT(2C) serotononergic, D(1) and D(2)
      dopaminergic, alpha (1) and alpha (2) adrenergic receptors by radioligand assays.
      The results show weak affinity to 5-HT(1A) only for the aqueous extract of V.
      adscendens and no affinity for 5-HT(2A), 5-HT(2C) serotononergic receptors, alpha
      (1) and alpha(2) adrenergic receptors and D(2) receptors. As it regards D(1)
      receptors, only for the methanolic extract the IC(50) value was determinable. The
      data obtained for I. herbstii extracts have shown a low affinity for the 5-HT(1A)
      receptor (22.44%) and no affinity for 5-HT(2A) receptor. Otherwise these extracts
      showed affinity for 5-HT(2C) receptor but only for the methanolic extract the
      IC(50) value (inhibitory concentration 50%) was: 34.8 microg/ml. The B. arborea
      aqueous extract displayed weak affinity for all receptors tested, the highest
      levels of inhibition at the maximum concentration tested (125 microg/ml) were 38%
      for the 5-HT(1A), 16% for the 5-HT(2A) and 39% for the 5-HT(2C) receptor. The
      results of our experiments indicate that V. adscendens, Iresine herbstii and
      Brugmansia arborea were able to interact with the central 5-HT receptors thus
      confirming their ritual use.

PMID- 18045211
TI  - Peptide-based soft materials as potential drug delivery vehicles.
AB  - Emerging concepts in the construction of nanostructures hold immense potential in
      the areas of drug delivery and targeting. Such nanoscopic assemblies/structures,
      similar to natural proteins and self-associating systems, may lead to the
      formation of programmable soft structures with expanded drug delivery options and
      the capability to circumvent first-pass metabolism. This article aims to
      illustrate key recent developments and innovative bioinspired design paradigms
      pertaining to peptide-containing self-assembled tubular and vesicular soft
      structures. Soft structures are composed of components that self-assemble to
      reveal diverse morphologies stabilized by weak, noncovalent interactions.
      Morphological properties of such structures and their ability to encapsulate
      drugs, biologicals and bioactive small molecules, with the promise of targeted
      delivery, are discussed.

PMID- 18045212
TI  - Targeting of Th1-associated chemokine receptors CXCR3 and CCR5 as therapeutic
      strategy for inflammatory diseases.
AB  - CXCR3 and CCR5 are chemokine receptor that are predominantly expressed on the
      surface of Th1 polarized T cells. In a variety of human and experimental
      autoimmune diseases the enhanced expression of CXCR3 and CCR5 binding chemokine
      ligands is followed by the recruitment of CXCR3- and CCR5-positive T cells,
      indicating an important role for these chemokine receptors in T cell-mediated
      tissue damage. In this review, we summarize a number of in vivo studies available
      on the neutralization of CXCR3 and CCR5 in inflammatory disease, and specifically
      focus on the potential therapeutic effects of CXCR3 and CCR5 blockade in human
      autoimmune disease and organ transplantation.

PMID- 18045213
TI  - Regression methods for developing QSAR and QSPR models to predict compounds of
      specific pharmacodynamic, pharmacokinetic and toxicological properties.
AB  - Quantitative structure-activity relationship (QSAR) and quantitative structure
      property relationship (QSPR) models have been extensively used for predicting
      compounds of specific pharmacodynamic, pharmacokinetic, or toxicological property
      from structure-derived physicochemical and structural features. These models can
      be developed by using various regression methods including conventional
      approaches (multiple linear regression and partial least squares) and more
      recently explored genetic (genetic function approximation) and machine learning
      (k-nearest neighbour, neural networks, and support vector regression) approaches.
      This article describes the algorithms of these methods, evaluates their
      advantages and disadvantages, and discusses the application potential of the
      recently explored methods. Freely available online and commercial software for
      these regression methods and the areas of their applications are also presented.

PMID- 18045214
TI  - Privileged structures: a useful concept for the rational design of new lead drug
      candidates.
AB  - Privileged structures are defined as molecular frameworks which are able of
      providing useful ligands for more than one type of receptor or enzyme target by
      judicious structural modifications. In the present work, we describe some
      examples and applications of the usefulness of the privileged structure concept
      for the structural design of new drug candidates, by discussing the eligibility
      of such motifs, including the identification of the N-acylhydrazone template as
      privileged structures.

PMID- 18045215
TI  - Beneficial or detrimental effects of carotenoids contained in food: cell culture
      models.
AB  - Epidemiological studies have suggested a correlation between consumption of
      carotenoid-rich food and incidence of chronic diseases. In this review chemical
      structure, bioavailability and mechanisms of action of carotenoids most
      represented in human diet, mainly beta-carotene and lycopene, are reported, with
      focus on results obtained with cells in culture.

PMID- 18045216
TI  - Peroxisome proliferator-activated receptor agonists as potential therapeutic
      agents in multiple sclerosis.
AB  - Peroxisome proliferator-activated receptors (PPARs) have been extensively studied
      for gene regulation in glucose and lipid metabolism. It has been recently
      implicated that PPARs regulate cellular proliferation and inflammatory responses;
      some agonists for PPARs ameliorate experimental autoimmune encephalomyelitis, a
      model of multiple sclerosis (MS) in humans. This article will outline current
      experimental evidence suggesting potential clinical benefits for patients with
      MS.

PMID- 18045217
TI  - Molecular targets of FoxP3+ regulatory T cells.
AB  - The important roles of FoxP3+ T cells in many immunological or cancerous diseases
      are now well established. The research field is now moving in the direction to
      fine-control the generation, migration, expansion, and function of FoxP3+ cells
      in an effort to prevent and cure specific types of diseases. Potential molecular
      targets to regulate FoxP3+ T cells are reviewed in this article.

PMID- 18045218
TI  - Histidine kinases as antimicrobial targets: prospects and pitfalls.
AB  - Histidine kinases are ubiquitous molecular sensors that are used by bacteria to
      detect and respond to a myriad of environmental signals. They are attractive
      antimicrobial targets because of their roles in mediating the virulence of
      pathogenic organisms, as well as the ability of bacteria to resist host defenses
      and develop resistance to antibiotics. In this review, we discuss the challenges
      involved in developing specific inhibitors of this highly diverse group of
      kinases.

PMID- 18045219
TI  - Viral elements sense tumorigenic processes: approaching selective cancer therapy.
AB  - Viruses can produce viral oncoproteins that drive multiple genetic alterations as
      the consequence of neoplastic transformation. Viral proteins encoded by onco
      related viruses such as polyomavirus SV40 or Epstein-Barr virus are involved in
      cellular processes resulting in imbalance between proliferation and cell death,
      knowledge of which continues to be crucial for combating cancer. On the other
      hand, viruses also generate viral components that, from a cold viral protein, can
      become a tumor-selective killer by sensing cellular tumorigenic hallmarks. For
      instance, the avian virus derived apoptin protein has been proven to induce tumor
      regression in various pre-clinical animal models without showing detectable side
      effects. In particular, apoptin-interacting protein partners such as components
      of the anaphase promoting complex were identified as potential anticancer drug
      targets. The adenovirus-derived protein E4orf4, another viral protein with tumor
      specific apoptosis characteristics, has been proven to interact with the tumor
      suppressor protein phosphatase 2A. This review aims to describe recent studies
      with representative viral elements that have contributed to our understanding of
      critical tumorigenic processes and have conferred an impact on the development of
      novel anti-cancer therapies.

PMID- 18045220
TI  - RNA interference as a tool for Alzheimer's disease therapy.
AB  - RNA interference is a biological process that controls gene silencing in all
      living cells. Targeting the RNA interference system represents a novel
      therapeutic strategy able to intercede with multiple disease-related genes and to
      target many neurodegenerative diseases. Recently, the design of small interfering
      RNA-selective compounds has become more straightforward because of the
      significant progress made in predictive modeling for new therapeutic approaches.
      Although in vivo delivery of RNA interference remains a significant obstacle, new
      data show that RNAi blocks gene function in vivo, suggesting a potential
      therapeutic approach for humans. Some groups have demonstrated the efficacy of
      RNAi therapy in Alzheimer's disease. Results, based on animal models, show a down
      regulation of the amyloid precursor protein and a consequent reduction of the
      amyloid-beta peptide accumulation in the brain or the inactivation of beta
      secretase (BACE1). Indeed, lentiviral vectors expressing siRNAs targeting BACE1
      reduce amyloid production and the neurodegenerative and behavioural deficit in
      APP transgenic mice. This review highlights recent advances in RNA research and
      focuses on strengths and weaknesses of RNAi compounds in Alzheimer's disease.

PMID- 18045221
TI  - Overview of anti-tuberculosis (TB) drugs and their resistance mechanisms.
AB  - One-third of the world's population is infected with Mycobacterium (M.)
      tuberculosis. Tuberculosis continues to be the most common infectious cause of
      death and still has a serious impact, medically, socially and financially.
      Multidrug-resistant tuberculosis (MDR-TB), caused by tubercle bacilli that are
      resistant to at least isoniazid and rifampin, is among the most worrisome
      elements of the pandemic of antibiotic resistance because TB patients for whom
      treatment has failed have a high risk of death. Drugs used to treat tuberculosis
      are classified into first-line and second-line agents. First-line essential anti
      tuberculosis agents are the most effective, and are a necessary component of any
      short-course therapeutic regimen. The drugs in this category are isoniazid,
      rifampin, ethambutol, pyrazinamide and streptomycin. Second-line anti
      tuberculosis drugs are clinically much less effective than first-line agents and
      elicit severe reactions much more frequently. These drugs include para
      aminosalicylic acid (PAS), ethionamide, cycloserine, amikacin and capreomycin.
      New drugs, which are yet to be assigned to the above categories, include
      rifapentine, levofloxacin, gatifloxacin and moxifloxacin. Recently there has been
      much development in the molecular pharmacology of anti-tuberculosis drugs. This
      review summarizes information for isoniazid, rifampicin, ethambutol,
      pyrazinamide, and fluoroquinolones, and describes their resistance mechanisms.

PMID- 18045222
TI  - The molecular nature and consequences of lipoprotein (a)'s association with
      platelets.
AB  - Lipoprotein (a) (Lp (a)) may be pro-thrombotic in humans due to its
      apolipoprotein (a) (apo(a))-mediated decreases in fibrinolysis. Such decreased
      fibrinolysis arises putatively from interference with plasminogen conversion to
      plasmin due to the considerable homology between apolipoprotein (a) and
      plasminogen. However, in vitro, most studies have shown that human Lp (a)
      decreases agonist-stimulated platelet aggregation while in vivo it appears to
      decrease aggregation as implied by increased bleeding times with higher blood
      serum concentrations of Lp(a). Lp (a) binding to platelets mediated by apo (a)
      increases platelet intracellular c-AMP levels in resting platelets, and decreases
      platelet production of thromboxane A2 and fibrinogen binding to platelets all of
      which reduce platelet aggregation. One, though not the only, explanation of these
      conflicting data may be that Lp(a) self-regulates its interference with
      fibrinolysis by reducing platelet aggregation and platelet binding of fibrinogen
      and hence the degree of requirement for fibrinolysis. However, it is concluded
      more in vivo work needs to be done to fully understand whether, if at all, Lp(a)
      in varying concentrations and isoforms, favours reduced platelet aggregation or
      fibrinolysis.

PMID- 18045223
TI  - Conservation of average hydrophobicity of apolar aminoacids in polypeptides
      constituting same glycosyl hydrolase sub-family enzymes.
AB  - Polypeptides constituting the same functional enzyme in cells of different
      origins have small sequence similarities among themselves. Amino acid analysis
      reveals that each glycosyl hydrolase sub-family polypeptides conserves an average
      hydrophobicity value for total constituent apolar amino acids. The value may be a
      measure of the driving force present in the polypeptide for designed primary
      collapse for three-dimensional active site formation.

PMID- 18045224
TI  - Biologically active peptides interacting with the G protein-coupled formylpeptide
      receptor.
AB  - Leucocytes accumulate at sites of inflammation and microbial infection in
      response to locally produced chemotactic factors. N-formylpeptides produced by
      Gram negative bacteria were among the first chemotactic factors structurally
      defined which signal through G protein-coupled formylpeptide receptor (FPR) and
      FPR-like 1 (FPRL1) expressed by phagocytic leukocytes in human and in mouse
      homogogues mFPR and mFPR2. During the past few years, a number of pathogen- and
      host-derived agonists/antagonists for FPR, FPRL1 and another FPR variant FPR-like
      2 (FPRL2) have been identified. Activation of formylpeptide receptors (FPRs) in
      phagocytic leukocytes by agonists results in increased cell chemotaxis,
      phagocytosis, and release of pro-inflammatory mediators. Peptide agonists for
      FPRs have also been shown to possess immune adjuvant activity when injected in
      mice. In addition, FPR aberrantly expressed on highly malignant human
      glioblastoma cells promotes tumor cell migration, proliferation and production of
      vascular endothelial growth factor in response to agonists released by necrotic
      tumor cells. Therefore, formylpeptide receptor ligands, by interacting with FPRs,
      play important roles in host defense and in the rapid progression of human
      glioblastoma.

PMID- 18045225
TI  - Freezing effect on chirality generation of DL-alanine-N-carboxy-anhydride
      oligomerization in aqueous solution.
AB  - This article is concerned with a study of the role of ice in the synthesis of
      oligopeptides containing L- or D-enantiomeric excess (ee) from racemic alanine.
      With this aim, the oligomerization of DL-alanine-N-carboxyanhydride was
      investigated by keeping this activated derivative in liquid (+22 degrees C) or
      frozen (-20 degrees C) aqueous solutions for 30 days. The aqueous solution of the
      peptide mixtures were gel-filtered and the aliquots of the fractions were
      completely hydrolyzed to alanine monomers. These monomers were then derivatized
      with 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (Marfey's reagent) and analyzed
      by RP-HPLC to reveal the occasional enantiomeric excess of L- or D-Ala. The mass
      spectrometry of the gel-filtered fractions pointed to open-chain peptide mixtures
      together with a slight amount of cyclic ones, where the residue numbers ranged
      between 5-8. Our studies indicated that an enantiomeric excess of L- or D-Ala
      appeared in some oligopeptide fractions. Their excesses were significantly larger
      in the frozen than liquid solution. Speculations are made as concerns the
      implications of our findings in the events of prebiotic chemistry.

PMID- 18045226
TI  - Isolation and characterization of a trypsin-chymotrypsin inhibitor from the seeds
      of green lentil (Lens culinaris).
AB  - A Bowman-Birk type trypsin-chymotrypsin inhibitor was isolated from seeds of the
      legume green lentil (Lens culinaris) by means of affinity chromatography on Affi
      gel blue gel, ion exchange chromatography on Q-Sepharose, ion exchange
      chromatography by fast protein liquid chromatography (FPLC) on Mono Q and Mono S,
      and gel filtration by FPLC on Superdex 75. The trypsin-chymotrypsin inhibitor was
      bound on the first three types of chromatographic media. It appeared as a single
      16-kDa peak in gel filtration and a single 16-kDa band in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The trypsin inhibitory activity of the
      inhibitor was sensitive to the reducing agent dithiothreitol. It was completely
      abrogated after treatment with 10 mM dithiothreitol for 20 minutes. The protease
      inhibitor did not exert any inhibitory effect on hepatoma (Hep G2) and breast
      cancer (MCF 7) cell lines. There was no suppressive action on several fungal
      species including Botrytis cinerea, Fusarium oxysporum and Mycosphaerella
      arachidicola. It slightly inhibited the activity of HIV-1 reverse transcriptase,
      with an IC50 of 30 mM.

PMID- 18045227
TI  - Application of a chimeric synthetic peptide in the development of a serologic
      method for the diagnosis of hepatitis G virus infection.
AB  - New putative antigenic peptides corresponding to the N- and C-terminal of the E2
      envelope protein of GBV-C/HGV were synthesized using solid-phase chemistry. The
      antigens were obtained in linear and chimeric forms with the main aim of
      improving the sensitivity of the enzyme immunoassays. Furthermore, CD and FTIR
      have been used in conjunction to characterize their conformational changes
      showing that the chimeric peptide presents a more ordered secondary structure
      than its parent peptides.

PMID- 18045228
TI  - Digital coding of amino acids based on hydrophobic index.
AB  - Analysis of amino acid sequences can provide useful insights into the tertiary
      structures of proteins and their biological functions. One of the critical
      problems in amino acid analysis is how to establish a digital coding system to
      better reflect the properties of amino acids and their degeneracy. Based on the
      hydrophobic index, a one-to-one relationship has been established between the
      amino acid sequence and the digital signal process. Such a "bridge" will make it
      possible to apply all the existing powerful methods in the signal processing area
      to analysis of the amino acid sequences.

PMID- 18045229
TI  - Co-expression and purification of recombinant human insulin-like growth factor II
      and insulin-like growth factor binding protein-6 in Pichia pastoris yeast.
AB  - For the preparation of the complex of IGF-II and IGFBP-6, a co-expression vector
      containing two copies of human IGF-II and IGFBP-6 expression cassette was
      constructed with alcohol oxidase (AOX1) promoter and secretion signal sequence of
      alpha-factor, and transformed to Pichia pastoris yeast. Through a purification
      procedure involving anion-exchange chromatography and gel filtration, a complex
      of IGF-II with IGFBP-6 was obtained. An additional C-terminal sequence of IGFBP-6
      (CS-BP6) was found to be bound to this complex. Dynamic light scattering showed
      that this complex was very stable and homogenous in solution. Western blotting
      based on non-reducing Tricine-SDS-PAGE indicated that IGF-II expression coupled
      with IGFBP-6 might significantly avoid the mispairing of disulfide bonds compared
      with the IGF-II expressed alone.

PMID- 18045230
TI  - Expression, purification, and immunological characterization of Cr PI.
AB  - An efficient preparation of Periplaneta americana nymphae allergen, Cr PI (54
      kDa) is described. It was expressed as a GST-tag fusion protein in Escherichia
      coli, strain BL21 (DE3). Expression of recombinant Cr PI (rCr PI),
      denaturation/renaturation of the inclusion bodies and the effects of protein and
      L-arginine concentration on inclusion body aggregation were optimized. The fusion
      protein was purified by affinity chromatography and size exclusion
      chromatography, and Cr PI fusion protein was purified to >95%. rCr PI bound
      strongly to IgE in the sera of individuals with cockroach allergies as shown by
      western blot and ELISA. Highly refolded and purified recombinant protein was
      obtained, providing a basis for the large-scale preparation of Cr PI allergen.

PMID- 18045231
TI  - Inhibition of sea urchin fertilization by plant lectins.
AB  - Effects of plant lectins on sea urchin (Lytechinus variegatus) fertilization and
      a partial characterization of lectin-binding involved in the process were
      evaluated. IC50 doses for inhibition of fertilization varied from 4.1 to 135.5
      microg/ml when the lectins were pre-incubated with sperms and from 0.7 to 33.4
      microg/ml when pre-incubated with eggs. Such effects were reversed when the
      lectins were heat inactivated. FITC-labeled lectins bound egg surfaces while
      their denatured forms did not. Glucose/mannose specific lectins bound weaker to
      eggs when pre-incubated with the glycoprotein bovine lactotransferrin. None of
      the glycoproteins assayed diminished FITC patterns of the Gal/GalNAc binding
      lectins. Pre-incubation of Glucose/mannose binding lectins with eggs did not
      alter binding of Gal/GalNAc lectins. Lectins with distinct competencies for
      binding monosaccharide and glycoconjugates were able to inhibit sea urchin
      fertilization.

PMID- 18045232
TI  - Protein-protein and protein-ligand interactions studied by electrospray
      ionization mass spectrometry.
AB  - Preservation of non-covalent interactions in biopolymer mass spectrometry offers
      new approaches to binding analysis. Recent work from our laboratory is reviewed
      here and discussed with reference to recent literature in the field. Three issues
      are considered in particular: hydrophobically stabilized complexes, pH-dependent
      transitions, and linked protein-ligand and protein-protein binding equilibria.

PMID- 18045233
TI  - Robust quantitative modeling of peptide binding affinities for MHC molecules
      using physical-chemical descriptors.
AB  - Major histocompatibility complex (MHC) molecules bind short peptides resulting
      from intracellular processing of foreign and self proteins, and present them on
      the cell surface for recognition by T-cell receptors. We propose a new robust
      approach to quantitatively model the binding affinities of MHC molecules by
      quantitative structure-activity relationships (QSAR) that use the physical
      chemical amino acid descriptors E1-E5. These QSAR models are robust, sequence
      based, and can be used as a fast and reliable filter to predict the MHC binding
      affinity for large protein databases.

PMID- 18045234
TI  - Design, synthesis and biological evaluation of antipicornaviral pyrrole
      containing peptidomimetics.
AB  - A series of new peptidomimetics based on the tripeptide sequence Z-Leu-Phe-Gln-OH
      were synthesized, with ten of these including the alpha-nitrogen atom of the N
      terminal amino acid incorporated into the pyrrole cycle. The synthesized
      compounds were tested for antiviral activity by agar-diffusion plaque inhibition
      test against Coxsackievirus B1 replication in FL cell. Four of the products were
      observed to possess an antiviral activity, which was proven to be significant for
      one product. N-terminal pyrrole moiety and C-terminal free carboxyl function are
      available in all active compounds. On the other hand, their corresponding -OBzl
      and -Obu t esters are inactive.

PMID- 18045235
TI  - Crystallization and preliminary x-ray studies of the unliganded wild-type bovine
      thrombin.
AB  - Wild type of bovine thrombin has been crystallized in a ligand-free form by the
      hanging drop vapor diffusion method with polyethylene glycol 4000 and 2-propanol.
      The crystals belong to space group P4 3 2 12 with unit cell parameters of a = b =
      87.7 A, c = 195.9 A. X-ray diffraction data were collected to 2.8 A resolution.

PMID- 18045236
TI  - Cloning, expression, purification, characterization, crystallization and x-ray
      diffraction of bifunctional pyrimidine deaminase/reductase from Shigella flexneri
      2a.
AB  - Bifunctional pyrimidine deaminase/reductase (RibD) plays an important role during
      riboflavin biosynthesis in many microorganisms. The 40.4 kDa RibD from Shigella
      flexneri 2a has been cloned, expressed, purified and characterized. Three
      Crystals of RibD have been obtained by the hanging-drop technique at 291 K using
      PEG 20k or NaCl as precipitant. The RibD crystal using PEG 20k as precipitant
      diffracted to 2.5A.

PMID- 18045237
TI  - Expression, purification, crystallization and preliminary x-ray analysis of Cyan
      fluorescent protein CyPet.
AB  - The technique of fluorescence (or Forster) resonance energy transfer (FRET) is
      widely used to observe bimolecular interaction in living cells. Cyan and yellow
      fluorescent proteins are the most widely used pair in FRET analysis. CyPet and
      YPet are two newly optimized fluorescent proteins that have much better dynamic
      range and sensitivity than CFP/YFP pair, although the crystallographic structure
      and the mechanism of better fluorescent characteristics of CyPet are still
      unknown. We have expressed the cyan fluorescent protein CyPet using pT7
      prokaryocyte expression system in Escherichia coli strain Rosetta (DE3) pLysS by
      auto-induction. After purification, the recombinant CyPet protein was
      crystallized by hanging drop vapor diffusion technique and could diffract to
      2.55A resolution. The data showed that the orthorhombic CyPet crystal was in
      space group P212121 with unit cell parameters (51.55, 61.53, 63.36) and contained
      one molecule in one asymmetric unit.

PMID- 18045239
TI  - The association between protein S levels and anticoagulant activity of tissue
      factor pathway inhibitor type 1.

PMID- 18045238
TI  - EGF and amphiregulin differentially regulate Cbl recruitment to endosomes and EGF
      receptor fate.
AB  - EGF-R [EGF (epidermal growth factor) receptor] ligands can promote or inhibit
      cell growth. The biological outcome of receptor activation is dictated, at least
      in part, by ligand-specified patterns of endocytic trafficking. EGF-R trafficking
      downstream of the ligands EGF and TGF-alpha (transforming growth factor-alpha)
      has been investigated extensively. However, less is known about EGF-R fates
      induced by the ligands BTC (betacellulin) and AR (amphiregulin). We undertook
      comparative analyses to identify ligand-specific molecular events that regulate
      EGF-R trafficking and degradation. EGF (17 nM) and BTC (8.5 nM) induced
      significant EGF-R degradation, with or without ectopic expression of the
      ubiquitin ligase Cbl. Human recombinant AR (17 nM) failed to affect receptor
      degradation in either case. Notably, levels of ligand-induced EGF-R
      ubiquitination did not correlate strictly with receptor degradation. Dose
      response experiments revealed that AR at a saturating concentration was a partial
      agonist at the EGF-R, with approx. 40% efficacy (relative to EGF) at inducing
      receptor tyrosine phosphorylation, ubiquitination and association with Cbl. EGF-R
      down-regulation and degradation also were compromised upon cell stimulation with
      AR (136 nM). These outcomes correlated with decreased degradation of the Cbl
      substrate and internalization inhibitor hSprouty2. Downstream of the hSprouty2
      checkpoint in AR-stimulated cells, Cbl-free EGF-R was incorporated into endosomes
      from which Cbl-EGF-R complexes were excluded. Our results suggest that the AR
      specific EGF-R fate results from decreased hSprouty2 degradation and reduced Cbl
      recruitment to underphosphorylated EGF-R, two effects that impair EGF-R
      trafficking to lysosomes.

PMID- 18045240
TI  - Immunologic and structural analysis of eight novel domain-deletion beta3 integrin
      peptides designed for detection of HPA-1 antibodies.
AB  - BACKGROUND: The single-nucleotide polymorphism (SNP) rs5918 in the ITGB3 gene
      defines the human platelet antigen-1 (HPA-1) system encoding a Leu (HPA-1a) or
      Pro (HPA-1b) at position 33. HPA-1 antibodies are clinically the most relevant in
      the Caucasoid population, but detection currently requires alpha(IIb)beta3
      integrin from the platelets of HPA-genotyped donors. OBJECTIVES: We set out to
      define the beta3 integrin domains required for HPA-1a antibody binding and
      produce recombinant soluble beta3 peptides for HPA-1 antibody detection. METHODS:
      We designed two sets (1a and 1b) of four soluble beta3 domain-deletion peptides
      (deltaSDL, deltabetaA, PSIHybrid, PSI), informed by crystallography studies and
      computer modeling. The footprints of three human HPA-1a-specific phage antibodies
      were defined by analyzing binding patterns to the beta3 peptides and canine
      platelets, and models of antibody-antigen interfaces were derived. Specificity
      and sensitivity for HPA-1a detection were assessed using sera from 140 cases of
      fetomaternal alloimmune thrombocytopenia (FMAIT). RESULTS: Fusion of recombinant
      proteins to calmodulin resulted in high-level expression in Drosophila S2 cells
      of all eight beta3 peptides. Testing of FMAIT samples indicated that deltabetaA
      Leu33 is the superior peptide for HPA-1a antibody detection, with 96% sensitivity
      and 95% specificity. The existence of type I and II categories of HPA-1a
      antibodies was confirmed by the study of HPA-1a phage antibody footprints and the
      reactivity pattern of clinical samples with the four beta3-Leu33 peptides, but
      there was no correlation between antibody category and clinical severity of
      FMAIT. CONCLUSIONS: Soluble recombinant beta3 peptides can be used for detection
      of clinical HPA-1a antibodies.

PMID- 18045241
TI  - Psychosocial factors and venous thromboembolism: a long-term follow-up study of
      Swedish men.
AB  - BACKGROUND: The link between psychosocial factors and coronary heart disease is
      well established, but although effects on coagulation and fibrinolysis variables
      may be implicated, no population-based study has sought to determine whether
      venous thromboembolism is similarly related to psychosocial factors. OBJECTIVE:
      To determine whether venous thromboembolism (deep vein thrombosis or pulmonary
      embolism) is related to psychosocial factors. PATIENTS/METHODS: A stress
      questionnaire was filled in by 6958 men at baseline from 1970 to 1973,
      participants in a cardiovascular intervention trial. Their occupation was used to
      determine socio-economic status. RESULTS: After a maximum follow-up of 28.8
      years, 358 cases of deep vein thrombosis and/or pulmonary embolism were
      identified through the Swedish hospital discharge and cause-specific death
      registries. In comparison with men who, at baseline, had no or moderate stress,
      men with persistent stress had increased risk of pulmonary embolism [hazard ratio
      (HR)=1.80, 95% CI: 1.21-2.67]. After multivariable adjustment, the HR decreased
      slightly to 1.66 (95% CI: 1.12-2.48). When compared with manual workers, men with
      white-collar jobs at intermediate or high level and professionals showed an
      inverse relationship between occupational class and pulmonary embolism (multiple
      adjusted HR=0.57, 95% CI: 0.39-0.83). Deep vein thrombosis was not significantly
      related to either stress or occupational class. CONCLUSION: Both persistent
      stress and low occupational class were independently related to future pulmonary
      embolism. The mechanisms are unknown, but effects on coagulation and fibrinolytic
      factors are likely.

PMID- 18045242
TI  - SYNCRIP, a component of dendritically localized mRNPs, binds to the translation
      regulator BC200 RNA.
AB  - Dendritic transport of (m)RNA molecules and localized translation at post
      synaptic sites is connected to synaptic plasticity and memory formation. Brain
      cytoplasmic RNA, 200nt (BC200 RNA) is a brain-specific, small non-messenger RNA
      with a somatodendritic distribution in primate neurons. The transcript is a
      component of a ribonucleoprotein particle that is thought to act as a regulator
      of decentralized translation in dendrites. To elucidate the cellular function of
      the BC200 ribonucleoprotein particle, we purified BC200 RNA-binding proteins from
      human brain. Here, we describe the interaction of human Synaptotagmin-binding
      cytoplasmic RNA interacting protein (SYNCRIP) with BC200 RNA. SYNCRIP was
      recently characterized as a component of large mRNA transport granules in neurons
      and is probably involved in local protein synthesis at post-synaptic sites. Our
      in vitro binding studies demonstrate that SYNCRIP interacts specifically with
      BC200 RNA and that binding is mediated through its N-terminal RNA recognition
      motifs and the internal A-rich region of BC200 RNA, respectively. Furthermore,
      immunoprecipitation experiments indicate an in vivo association of SYNCRIP and
      BC200 RNA in human brain. Thus, SYNCRIP may recruit BC200 RNA into mRNA transport
      complexes involved in the regulation of localized translation in dendrites.

PMID- 18045243
TI  - Genetic influences on behavioral inhibition and anxiety in juvenile rhesus
      macaques.
AB  - In humans and other animals, behavioral responses to threatening stimuli are an
      important component of temperament. Among children, extreme behavioral inhibition
      elicited by novel situations or strangers predicts the subsequent development of
      anxiety disorders and depression. Genetic differences among children are known to
      affect risk of developing behavioral inhibition and anxiety, but a more detailed
      understanding of genetic influences on susceptibility is needed. Nonhuman
      primates provide valuable models for studying the mechanisms underlying human
      behavior. Individual differences in threat-induced behavioral inhibition
      (freezing behavior) in young rhesus monkeys are stable over time and reflect
      individual levels of anxiety. This study used the well-established human intruder
      paradigm to elicit threat-induced freezing behavior and other behavioral
      responses in 285 young pedigreed rhesus monkeys. We examined the overall
      influence of quantitative genetic variation and tested the specific effect of the
      serotonin transporter promoter repeat polymorphism. Quantitative genetic analyses
      indicated that the residual heritability of freezing duration (behavioral
      inhibition) is h(2) = 0.384 (P = 0.012) and of 'orienting to the intruder'
      (vigilance) is h(2) = 0.908 (P = 0.00001). Duration of locomotion and hostility
      and frequency of cooing were not significantly heritable. The serotonin
      transporter polymorphism showed no significant effect on either freezing or
      orienting to the intruder. Our results suggest that this species could be used
      for detailed studies of genetic mechanisms influencing extreme behavioral
      inhibition, including the identification of specific genes that are involved in
      predisposing individuals to such behavior.

PMID- 18045244
TI  - Systematic review: nutritional therapy in paediatric Crohn's disease.
AB  - BACKGROUND: At least 25% of individuals diagnosed with Crohn's disease (CD) have
      onset of disease in childhood. Almost all children with CD have nutritional
      impairments, such as weight loss or stunting, at diagnosis or subsequently.
      Nutritional therapy (exclusive enteral nutrition) is established as a valid and
      effective treatment in paediatric CD. The advantages of this approach are
      induction of remission and control of inflammatory changes, mucosal healing,
      positive benefits to growth and overall nutritional status, and avoidance of
      other medical therapies. AIM: To provide a comprehensive up-to-date review of the
      roles of nutritional therapy in CD and of the data supporting this therapy.
      METHODS: A search of PubMed was performed with search terms 'enteral nutrition',
      'nutritional therapy', 'Crohn disease' and 'children'. Relevant articles were
      selected from this search. In addition, the reference lists of available articles
      were reviewed for further relevant articles. RESULTS: Nutritional therapy offers
      numerous benefits in the management of CD. Recent work has begun to elucidate the
      likely mechanisms of this therapy. These include direct mucosal anti-inflammatory
      effects and alteration of intestinal microflora. CONCLUSION: Further studies are
      required to define longer-term effects of nutritional therapy in patients with
      CD.

PMID- 18045245
TI  - Mouse models of human arrhythmia syndromes.
AB  - Sudden cardiac death stemming from ventricular arrhythmogenesis is one of the
      major causes of mortality in the developed world. Congenital and acquired forms
      of long QT syndrome (LQTS) are in turn associated with life threatening
      arrhythmias. Over the past decade our understanding of arrhythmogenic mechanisms
      in the setting of these diseases has increased greatly due to the creation of a
      number of animal models. Of these, the genetically amenable mouse has proved to
      be a particularly powerful tool. This review summarizes the congenital and
      acquired LQTS and describes the various mouse models that have been created to
      further probe arrhythmogenic mechanisms.

PMID- 18045248
TI  - A review of current approaches to identifying human genes involved in myopia.
AB  - The prevalence of myopia is high in many parts of the world, particularly among
      the Orientals such as Chinese and Japanese. Like other complex diseases such as
      diabetes and hypertension, myopia is likely to be caused by both genetic and
      environmental factors, and possibly their interactions. Owing to multiple genes
      with small effects, genetic heterogeneity and phenotypic complexity, the study of
      the genetics of myopia poses a complex challenge. This paper reviews the current
      approaches to the genetic analysis of complex diseases and how these can be
      applied to the identification of genes that predispose humans to myopia. These
      approaches include parametric linkage analysis, non-parametric linkage analysis
      like allele-sharing methods and genetic association studies. Basic concepts,
      advantages and disadvantages of these approaches are discussed and explained
      using examples from the literature on myopia. Microsatellites and single
      nucleotide polymorphisms are common genetic markers in the human genome and are
      indispensable tools for gene mapping. High throughput genotyping of millions of
      such markers has become feasible and efficient with recent technological
      advances. In turn, this makes the identification of myopia susceptibility genes a
      reality.

PMID- 18045249
TI  - Application of proteomic technology in eye research: a mini review.
AB  - Proteomics is a rapidly growing research area for the study of the protein
      cognate of genomic data. This review gives a brief overview of the modern
      proteomic technology. In addition to general applications of proteomics, we
      highlight its contribution to studying the physiology of different ocular
      tissues. We also summarise the published proteomic literature in the broad
      context of ophthalmic diseases, such as cataract, age-related maculopathy,
      diabetic retinopathy, glaucoma and myopia. The proteomic technology is a useful
      research tool and it will continue to advance our understanding of a variety of
      molecular processes in ocular tissues and diseases.

PMID- 18045250
TI  - New perspectives on keratoconus as revealed by corneal confocal microscopy.
AB  - Confocal microscopy (CM) of keratoconus is reviewed. In the Manchester
      Keratoconus Study (MKS), slit scanning CM was used to evaluate 29 keratoconic
      patients and light microscopy (LM) was performed on two of the keratoconic
      corneas post-keratoplasty. The findings of the MKS are compared with other CM
      studies. Consideration of the differences between studies of cell counts is
      confounded by the use of different experimental controls. A consensus exists
      among studies with respect to qualitative observations. The epithelium appears
      more abnormal with increasing severity of keratoconus. In severe disease, the
      superficial epithelial cells are elongated and spindle shaped, epithelial wing
      cell nuclei are larger and more irregularly spaced and basal epithelial cells are
      flattened. Bowman's layer is disrupted and split in the region of the cone and
      intermixed with epithelial cells and stromal keratocytes. Stromal haze and hyper
      reflectivity observed with CM correspond with apical scarring seen with the
      slitlamp biomicroscope (SLB). Hyper-reflective keratocyte nuclei are thought to
      indicate the presence of fibroblastic cells. Increased haze detected with CM is
      found with LM to be due to fibroblastic accumulation and irregular collagen
      fibres. Dark stromal bands observed with CM correlate with the appearance of
      Vogt's striae with SLB. Descemet's membrane appears normal with both CM and LM.
      Some evidence of endothelial cell elongation is observed with CM. The application
      of CM to ophthalmic practice has facilitated a greater understanding of medical
      and surgical approaches that are used to treat keratoconus. This review offers
      new perspectives on keratoconus and provides a framework, against which tissue
      changes in this visually debilitating condition can be studied in a clinical
      context in vivo using CM.

PMID- 18045251
TI  - Synthetic corneal inlays.
AB  - This review is based on the activities of the Vision Cooperative Research Centre
      (previously Cooperative Research Centre for Eye Research and Technology) Corneal
      Implant team from 1991 to 2007. The development of a synthetic polymer of
      perfluoropolyether (PFPE), meeting essential physical and biological
      requirements, for use as a corneal inlay is presented. Each inlay was placed in a
      corneal flap created with a microkeratome and monitored over a two-year period in
      a rabbit model. The results indicate that the PFPE implant shows excellent
      biocompatibility and biostability. As a result, a Phase 1 clinical trial is being
      conducted. Three years post-implantation, the PFPE inlays are exhibiting
      continued excellent biocompatibility. Corneal inlays made from PFPE are
      biocompatible with corneal tissue in the long term and offer a safe and
      biologically-acceptable alternative to other forms of refractive surgery.

PMID- 18045252
TI  - A review of the role of glial cells in understanding retinal disease.
AB  - Retinal vascular diseases such as diabetic retinopathy and retinopathy of
      prematurity are major causes of visual loss. Although the focus of a great deal
      of research has been on the aetiology of vascular growth, it is now emerging that
      anomalies in other retinal cell types, especially glial cells, occur very early
      in the course of the disease. Glial cells have major roles in every stage of
      disease, from the earliest subtle variations in neural function, to the
      development of epi-retinal membranes and tractional detachment. Therefore, having
      a firm understanding of the function of retinal glia is important in our
      understanding of retinal disease and is crucial for the development of new
      treatment strategies.

PMID- 18045253
TI  - A review of the potential to restore vision with stem cells.
AB  - Vision research involving stem cells is a rapidly evolving field. Animal
      experiments have shown that in response to environmental cues, stem cells can
      repopulate damaged retinas, regrow neuronal axons, repair higher cortical
      pathways, and restore pupil reflexes, light responses and basic pattern
      recognition. Viable corneas have been grown from stem cells and transplanted into
      humans. Similarly, human trials to repair damaged retinas in retinitis pigmentosa
      and age-related macular degeneration patients have produced preliminary
      successes. This review attempts to place the collective contributions toward stem
      cell/vision research into a broader clinical model of how stem cells might
      ultimately be used to restore the entire visual pathway.

PMID- 18045254
TI  - A web-based archive for topographic maps of retinal cell distribution in
      vertebrates.
AB  - Clinical and Experimental Optometry, in conjunction with Optometrists Association
      Australia and Professor Shaun P Collin of the University of Queensland, announce
      the launch of a web-based archive of previously published topographic maps of
      retinal cell distribution in vertebrates. At present, the archive boasts more
      than 770 different maps of the distribution of retinal neurons (for example,
      photoreceptors, bipolar cells, amacrine cells, horizontal cells and ganglion
      cells) in nearly 200 species within all vertebrate classes (Cephalospidomorpha,
      Actinopterygii, Sarcopterygii, Amphibia, Reptilia, Aves and Mammalia). The
      distribution of retinal neurons has been studied for more than 100 years and has
      become a powerful means of predicting the spatial resolving power of the eye and
      the retinal regions containing specialisations, such as areae centrales,
      horizontal streaks and foveae, where increased densities of neurons define the
      way in which a species visually samples its environment. The location of these
      retinal specialisations thereby identifies the part(s) of the visual field of
      critical importance for localising food and mates and for predator surveillance.
      The distribution of sampling elements even reflects the symmetry of a species'
      ecological habitat. The archive is a unique collection of most of the currently
      available retinal maps, which also presents relevant information, where known,
      about eye size, retinal cell density, retinal orientation, cell number, spatial
      resolving power and the type of specialisation, in addition to basic physical
      parameters of each species (body size, weight, sex and developmental stage). The
      archive is accessible at http://www.optometrists.asn.au/ceo/retinalsearch and
      will be updated regularly. The powerful database is interactive and freely
      available, providing the opportunity to upload both published and unpublished
      topographic maps. Following a review process, previously unpublished maps will be
      'published' and available online worldwide. It is hoped that this comprehensive
      new resource will provide not only an up-to-date method of accessing maps of the
      distribution of retinal neurons in individual species but also allow broader
      evolutionary comparisons of the visual capabilities, ecology, development and the
      type(s) of retinal specialisations found in vertebrates.

PMID- 18045255
TI  - The mobility of optometrists practising in Australia in 2005: do optometry
      graduates move to states without schools of optometry?
AB  - BACKGROUND: Three schools of optometry in the eastern states of Australia provide
      optometrists for the entire country. Concerns have been expressed about
      attracting optometrists to practise in the other states. This paper analyses the
      source of optometric qualification of optometrists practising in each state, to
      assess the proportion who have chosen to practise in a state different from that
      in which they qualified and to determine whether there are gender differences in
      preparedness to move to a different state. METHOD: Data on year and school of
      qualification, primary professional activity and current state or territory of
      practice were extracted from the Optometrists Association Australia database to
      determine a profile of place of qualification of optometrists in each state or
      territory of Australia in 2005. RESULTS: More than 77 per cent of practising
      optometrists from Australian schools practised in the state where they graduated.
      The majority of optometrists for the Australian Capital Territory (ACT), South
      Australia (SA) and Western Australia (WA) were New South Wales graduates; the
      majority of Tasmanian optometrists were Victorian graduates. Optometrists from
      overseas accounted for 17.3, 24.6 and 19.9 per cent of optometrists in practice
      in SA, Tasmania and WA, respectively, but less than 7.5 per cent elsewhere. The
      highest number of optometrists who had qualified outside Australia practised in
      NSW. Female graduates from 2000 and later were more likely to move interstate
      than their male counterparts. DISCUSSION: Approximately 14 per cent of practising
      optometry graduates practised in states without schools, where 21 per cent of the
      population resided. This indicates some degree of mobility but the market needs
      to work further to match supply of optometric services to demand at state level.
      Further analysis is necessary to determine patterns of graduate movement in the
      years following graduation, to determine whether movement to different states is
      short- or long-term.

PMID- 18045256
TI  - Could the coefficient of variation (COV) of the corneal endothelium be
      overestimated when a centre-dot method is used?
AB  - BACKGROUND: Little has been published on the reliability of estimates of the
      coefficient of variation (COV) in cell area for human corneal endothelia. The
      present study compares two methods. METHODS: A non-contact specular micrograph
      (Topcon SP-2000P) was obtained from the central region of the corneal endothelium
      of 20 healthy myopic white European subjects, aged from 32 to 53 years, half of
      whom were successful long-term soft contact lens wearers. The captured image file
      was either assessed using a machine-based algorithm, in which 25 cells in the
      middle of the image were marked and their areas reported (designated as 'centre
      dot' method) or by a manual method, by which all the cells in the image were
      outlined on very high magnification prints of the endothelia and the cell areas
      measured by a manual digitiser in stream mode. The average cell area was used to
      calculate the endothelial cell density (ECD), while the COV was calculated from
      the standard deviation (SD) of the cell area measures. RESULTS: Identical mean
      cell area values were found (392 microm(2)) with the two methods, a marginally
      higher ECD estimate (2,594 versus 2,569) with the centre-dot method (p = NS) but
      a much higher COV with the centre-dot method (43.8 versus 29.0 per cent). This
      highly statistically significant difference in COV (p < 0.001) was seen in both
      contact lens wearers and non-contact lens wearers. A Bland-Altman analysis
      reveals a bias in the centre-dot method, especially for the COV estimates, that
      appears to be linked to erroneous definition of a single large cell domain on any
      individual image. CONCLUSIONS: A centre-dot method can be reliably used to
      generate useful data on cell area and ECD but it should be used cautiously for
      estimates of polymegethism (COV).

PMID- 18045257
TI  - Combined therapy for vernal shield ulcer.
AB  - A 22-year-old male patient presented with complaints of pain and redness in the
      right eye. Slitlamp examination revealed giant papillae on both tarsal
      conjunctivae, bilateral punctate corneal epitheliopathy and a 2.9 x 2.9 mm
      epithelial defect in the right eye. The diagnosis was bilateral vernal
      keratoconjunctivitis with shield ulcer in the right eye. Treatment was commenced
      with prednisolone (1%) eye drops four times daily and sodium hyaluronate (0.1%)
      eye drops eight times daily. After one week, the patient had improved
      symptomatically but the epithelial defect remained unchanged. Topical
      cyclosporine (0.05%) applied eight times per day was added to the regimen of
      topical corticosteroid and artificial tears. Three weeks after commencing
      combined therapy, the shield ulcer had healed completely, leaving a corneal
      opacity that negatively stained with fluorescein. The patient was followed for
      five months and no recurrence of ulcer was noted, despite the discontinuation of
      topical cyclosporine and prednisolone. Simultaneous institution of topical
      corticosteroid, artificial tears and topical cyclosporine seems to augment the
      therapeutic efficacy of each other and may be a promising regime in the
      management of shield ulcer.

PMID- 18045258
TI  - Is herpes simplex virus keratitis a different disease in children?
AB  - Ocular infections resulting from herpes simplex viral infection can result in
      significant ocular morbidity. Crucial in preventing this complication is the need
      for appropriate diagnosis and initiation of treatment. In addition, most of the
      studies on herpes simplex viral infections involve adult populations. It is
      important to consider that children have a different progression of the disease
      process and may require an altered treatment regimen.

PMID- 18045259
TI  - Editorial: contribution of health systems to disease control.

PMID- 18045260
TI  - Short communication: patterns of chronic and acute diseases after natural
      disasters - a study from the International Committee of the Red Cross field
      hospital in Banda Aceh after the 2004 Indian Ocean tsunami.
AB  - OBJECTIVE: To assess the pattern of diseases in a natural disaster, which are not
      necessarily a direct consequence of the event but can impact on the way health
      assistance is to be provided. METHODS: Cross-sectional, record-based study in the
      International Committee of the Red Cross field hospital in Aceh, Indonesia,
      established immediately after the tsunami in 2004. Patients who presented to
      hospital from January 15 to 31, and whose diagnoses were available, were included
      in the study. RESULTS: One thousand one hundred and eighty-eight residents of
      Aceh participated. 43.5% of the diagnoses was chronic diseases. The odds of
      chronic vs. acute diseases increased by 16.4% per day up to January 23 [95%
      confidence interval (CI): 7.8-25.6%] and decreased thereafter by 13.1% (95% CI:
      6.6-19.1%) per day. The odds of acute diseases were 34% lower among females than
      males (95% CI: 16-49%) and 4.3 times higher among children than the rest of the
      population (95% CI: 2.4-7.6). There were relatively few trauma cases among
      females and children. CONCLUSIONS: Medical teams providing relief after acute
      disasters should be prepared to provide healthcare for chronic diseases too. A
      delay in the presentation of many acute conditions has implications for long-term
      health consequences of disasters, such as disability.

PMID- 18045261
TI  - Taxonomy and inventory of the cytospecies and cytotypes of the Simulium damnosum
      complex (Diptera: Simuliidae) in relation to onchocerciasis.
AB  - We provide an inventory of all named cytoforms of the Simulium damnosum complex
      (including those which are now considered invalid), along with all inversions
      that have been recorded (including synonyms and homonyms). There are 55 valid and
      distinct cytoforms known from the S. damnosum complex making it the largest
      sibling species complex of any vectors, and probably of any insect or other
      animal. All cytoforms are listed along with their fixed and diagnostic inversions
      and country distribution. There are 183 inversions known from the complex as a
      whole, of which 49% are fixed and/or diagnostic between cytoforms, and the
      fixed/diagnostic inversions seem to occur disproportionately on chromosome arm
      2L.

PMID- 18045262
TI  - Influence of larval density or food variation on the geometry of the wing of
      Aedes (Stegomyia) aegypti.
AB  - BACKGROUND AND METHOD: Variation in wing length among natural populations of
      Aedes (Stegomyia) aegypti (L.) (Diptera: Culicidae) is associated with different
      vectorial capacities. Geometric morphometrics allowed us to use a more powerful
      estimator of wing size ('centroid size'), as well as to visualize the variation
      of wing shape, to describe the effects of density or food variation at larval
      stage on 20 anatomical landmarks of the wing of A. aegypti. RESULTS: Almost
      perfect correlations between (centroid) size and larval density or size and
      larval food were observed in both sexes: a negative correlation with increasing
      density and a positive one with increasing amount of food. The allometric
      component of shape change was always highly significant, with stronger
      contribution of size to shape under food effects. Within each experiment, either
      food or density effects, and excluding extreme conditions, allometric trends were
      similar among replicates and sexes. However, they differed between the two
      experiments, suggesting different axes of wing growth. CONCLUSION: Aedes aegypti
      size is highly sensible to food concentration or population density acting at
      larval stages. As larger individuals could be better vectors, and because of the
      stronger effect of food concentration on size, vector control activities should
      pay more attention in eliminating containers with rich organic matter.
      Furthermore, as a simple reduction in larval density could significantly increase
      the size of the survivors, turning them into potentially better vectors, the
      control activities should try to obtain a complete elimination of the domestic
      populations.

PMID- 18045263
TI  - Detection of mutant P2 adenosine transporter (TbAT1) gene in Trypanosoma brucei
      gambiense isolates from northwest Uganda using allele-specific polymerase chain
      reaction.
AB  - OBJECTIVE: To assess the application of allele-specific PCR (AS-PCR) as a fast,
      cheap and reliable method for detecting mutant TbAT1 associated with melarsoprol
      relapse in Trypanosoma brucei gambiense isolates from northwest Uganda. METHODS:
      A total of 105 trypanosome isolates were analysed using SfaN1 restriction
      fragment length polymorphism (RFLP) and AS-PCR, the former used as the gold
      standard. Sensitivity, specificity, positive and negative predictive values of AS
      PCR as well as agreement between the tests were determined. RESULTS: Eleven
      trypanosome isolates had mutant TbAT1 while 94 exhibited the wild-type TbAT1
      genes. There was a highly significant agreement between SfaN1 RFLP and AS-PCR
      with kappa and intra-class correlation values of 1.0. The sensitivity and
      specificity of AS-PCR were both 100%, while the positive and negative predictive
      values were found to be equal to 1.0. Cost and time analyses were performed and
      AS-PCR was 4.3 times cheaper than SfaN1 RFLP, in addition to the less time
      required for its execution. CONCLUSION: AS-PCR should be the test of choice for
      screening for mutant TbAT1 in the ever-increasing numbers of field trypanosome
      isolates.

PMID- 18045264
TI  - Epidemiology and clinical features of pneumonia according to radiographic
      findings in Gambian children.
AB  - OBJECTIVE: To assess the effect of vaccines against pneumonia in Gambian
      children. METHODS: Data from a randomized, controlled trial of a 9-valent
      pneumococcal conjugate vaccine (PCV) were used. Radiographic findings,
      interpreted using WHO definitions, were classified as primary end point
      pneumonia, 'other infiltrates/abnormalities' pneumonia and pneumonia with no
      abnormality. We calculated the incidence of the different types of radiological
      pneumonia, and compared clinical and laboratory features between these groups.
      RESULTS: Among children who did not receive PCV, the incidence of pneumonia with
      no radiographic abnormality was about twice that of 'other infiltrates' pneumonia
      and three times that of primary endpoint pneumonia. Most respiratory symptoms,
      reduced feeding and vomiting occurred most frequently in children with primary
      endpoint pneumonia. These children were more likely to be malnourished, to have
      bronchial breath sounds or invasive bacterial diseases, and to die within 28 days
      of consultation than children in the other groups. Conversely, a history of
      convulsion, diarrhoea or fast breathing, malaria parasitaemia and isolation of
      salmonellae were commoner in children with pneumonia with no radiographic
      abnormality. Lower chest wall indrawing and rhonchi on auscultation were seen
      most frequently in children with 'other infiltrates/abnormalities' pneumonia.
      CONCLUSION: Primary endpoint pneumonia is strongly associated with bacterial
      aetiology and severe pneumonia. Since this category of pneumonia is significantly
      reduced after vaccination with Hib and pneumococcal vaccines, the risk-benefit of
      antimicrobial prescription for clinical pneumonia for children with increased
      respiratory rate may warrant re-examination once these vaccines are in widespread
      use.

PMID- 18045265
TI  - Healthcare-seeking behaviour and use of traditional healers after snakebite in
      Hlabisa sub-district, KwaZulu Natal.
AB  - OBJECTIVE: To quantify snakebite incidence in Hlabisa sub-district and examine
      healthcare seeking behaviour, focussing on the use of traditional healers and
      medications. METHODS: Snakebite incidence was calculated by retrospective
      register review at Hlabisa Hospital for the period 2000-2005 and at associated
      primary health care clinics for 2005. Fifty consecutive in-patient snakebite
      victims were interviewed. Treatment-seeking pathways, bite-to-admission times and
      factors associated with delay or use of traditional therapy were analysed.
      RESULTS: The annual hospital snakebite incidence was 53 bites per 100,000
      population. In 2005, combined hospital and community incidence was 58 per
      100,000. Eighty per cent of admitted snakebite victims used traditional medicine
      and 62.5% of these consulted a traditional health practitioner (THP). The median
      time until admission was 7 h 15 min (interquartile range: 4-14.25 h). The median
      time until THP consultation was 15 min (interquartile range 5-50 min). THP
      consultation was associated with bite-to-hospital admission delays of more than 6
      h [relative risk: 1.82, 95% confidence interval (CI): 1.09-3.03, P = 0.0016). Non
      statistically significant trends towards THP use were observed if hospital access
      was poor or if patients were younger than 9 years.

PMID- 18045266
TI  - Editorial.

PMID- 18045267
TI  - Inverse modeling methods for indoor airborne pollutant tracking: literature
      review and fundamentals.
AB  - Reduction in indoor environment quality calls for effective control and
      improvement measures. Accurate and prompt identification of contaminant sources
      ensures that they can be quickly removed and contaminated spaces isolated and
      cleaned. This paper discusses the use of inverse modeling to identify potential
      indoor pollutant sources with limited pollutant sensor data. The study reviews
      various inverse modeling methods for advection-dispersion problems and summarizes
      the methods into three major categories: forward, backward, and probability
      inverse modeling methods. The adjoint probability inverse modeling method is
      indicated as an appropriate model for indoor air pollutant tracking because it
      can quickly find source location, strength and release time without prior
      information. The paper introduces the principles of the adjoint probability
      method and establishes the corresponding adjoint equations for both multi-zone
      airflow models and computational fluid dynamics (CFD) models. The study proposes
      a two-stage inverse modeling approach integrating both multi-zone and CFD models,
      which can provide a rapid estimate of indoor pollution status and history for a
      whole building. Preliminary case study results indicate that the adjoint
      probability method is feasible for indoor pollutant inverse modeling. PRACTICAL
      IMPLICATIONS: The proposed method can help identify contaminant source
      characteristics (location and release time) with limited sensor outputs. This
      will ensure an effective and prompt execution of building management strategies
      and thus achieve a healthy and safe indoor environment. The method can also help
      design optimal sensor networks.

PMID- 18045268
TI  - Identification of contaminant sources in enclosed spaces by a single sensor.
AB  - To protect occupants from infectious diseases or possible chemical/biological
      agents released by a terrorist in an enclosed space, such as an airliner cabin,
      it is critical to identify gaseous contaminant source locations and strengths.
      This paper identified the source locations and strengths by solving inverse
      contaminant transport with the quasi-reversibility (QR) and pseudo-reversibility
      (PR) methods. The QR method replaces the second-order diffusion term in the
      contaminant transport equation with a fourth-order stabilization term. By using
      the airflow pattern calculated by computational fluid dynamics (CFD) and the time
      when the peak contaminant concentration was measured by a sensor in downstream,
      the QR method solves the backward probability density function (PDF) of
      contaminant source location. The PR method reverses the airflow calculated by CFD
      and solves the PDF in the same manner as the QR method. The position with the
      highest PDF is the location of the contaminant source. The source strength can be
      further determined by scaling the nominal contaminant concentration computed by
      CFD with the concentration measured by the sensor. By using a two-dimensional and
      a three-dimensional aircraft cabin as examples of enclosed spaces, the two
      methods can identify contaminant source locations and strengths in the cabins if
      the sensors are placed in the downstream location of the sources. The QR method
      performed slightly better than the PR method but with a longer computing time.
      PRACTICAL IMPLICATIONS: The paper presents a method that can be used to find a
      gaseous contaminant source location and determine its strength in enclosed spaces
      with the data of contaminant concentration measured by one sensor. The method can
      be a very useful tool to find where, what, and how the contamination has
      happened. The method is also useful for optimally placing sensors in enclosed
      spaces. The results can be applied to develop appropriate measures to protect
      occupants in enclosed environments from infectious diseases or
      chemical/biological warfare agents released by a terrorist.

PMID- 18045269
TI  - An experimental parametric study of VOC from flooring systems exposed to alkaline
      solutions.
AB  - This study outlined the influence of a number of parameters affecting the
      emission rate from one of the largest sources of VOC in the building stock in the
      Nordic countries. This source is flooring systems of polyvinyl chloride or
      linoleum attached to a substrate of moisture damaged or insufficiently dried
      concrete. The secondary emission rate of degradation products was measured, with
      the Field and Laboratory Emission Cell, on different flooring systems consisting
      of three different floorings and three adhesives, exposed to three different
      aqueous solutions in the range of 11-13.1 pH. The conclusion drawn in this study
      is that the great majority of the secondary emission originates from the floor
      adhesive. The occurrence of adhesive and the amount of adhesive used have a
      significant influence on the emission rate. A critical pH value for degradation
      of the adhesive seems to lie somewhere between 11 and 13 pH. PRACTICAL
      IMPLICATIONS: When designing a floor system or a renovation of a damaged flooring
      system, it is important to bear in mind the influence of parameters that may
      drastically shorten the service life. Flooring adhesive may decompose in a moist
      alkaline environment and give rise to unacceptable secondary emission rates.

PMID- 18045270
TI  - Building-related symptoms and inflammatory potency of dust from office buildings.
AB  - The aim was to investigate the association between building-related symptoms
      (BRS) in office buildings and the inflammatory potency of dust (PD). Furthermore,
      the association between dust potency and various building characteristics was
      investigated. Occupants of 22 office buildings received a retrospective
      questionnaire about BRS (2301 respondents). Dust was collected from groups of
      offices and building characteristics were recorded. The potency of a dust sample
      to induce interleukin-8 (IL-8) secretion from the lung epithelial cell line A549
      was measured as the slope of the initial linear part of the concentration
      response curve. Symptoms of the central nervous system (CNS) were associated with
      the potency of surface dust (OR = 1.4). This association may be due to an
      association between an index of CNS symptoms and dust potency in offices of 1-6
      occupants (OR = 1.5). No single symptoms correlated with the potency of surface
      dust. The PD was not related to single building factors. The inflammatory PD may
      be used as an integrated proxy measure of biologically active compounds in dust,
      reflecting health relevant properties of the dust. PRACTICAL IMPLICATIONS: The
      potency of surface dust may be used as a crude measurement of the chemical and
      biological exposures present in the building, and being associated with the
      development of central nervous system symptoms. However, additional research is
      needed to establish the predictive value of the potency of surface dust.

PMID- 18045271
TI  - Indoor air pollution from biomass combustion and respiratory symptoms of women
      and children in a Zimbabwean village.
AB  - Rural areas of developing countries are particularly reliant on biomass for
      cooking and heating. Women and children in these areas are often exposed to high
      levels of pollutants from biomass combustion that is associated with a range of
      respiratory symptoms. Domestic exposure to carbon monoxide (CO) and respirable
      particles (RSPs) in association with respiratory symptoms among women and
      children in Zimbabwe was investigated in 48 households. Health status and
      household characteristics were also recorded. In this study, indoor levels of CO
      and RSPs exceeded World Health Organization (WHO) air quality guidelines in over
      95% of kitchens. The level of indoor air pollutants was associated with the area
      of kitchen windows and the length of cooking time combined with the level of fire
      combustion. Prevalence of respiratory symptoms was 94% for women and 77% for
      children. In addition, women reporting respiratory symptoms were exposed to
      higher levels of RSPs when compared with those reporting no respiratory symptoms.
      The study results indicated that levels of indoor air pollutants in rural
      Zimbabwe may contribute to respiratory symptoms in both women and children.
      PRACTICAL IMPLICATIONS: Levels of respirable particles and carbon monoxide in
      kitchens in rural Zimbabwe are unacceptably high and measures to reduce levels
      should be undertaken. Based on the study findings, recommendations for increasing
      the area of kitchen windows may be considered as a practical method of reducing
      indoor air pollutants in rural Zimbabwe.

PMID- 18045272
TI  - Effects of environmental tobacco smoke on respiratory health of boys and girls
      from kindergarten: results from 15 districts of northern China.
AB  - The effects of childhood environmental tobacco smoke (ETS) exposure on
      respiratory symptoms were investigated in 6053 kindergarten-aged children
      residing in 15 districts of northern China. Responses to a self-administered
      questionnaire completed by parents of children from 30 kindergartens were used to
      ascertain children with persistent cough, persistent phlegm, asthma symptom,
      current asthma, wheeze and wheeze without asthma. In first 2 years ETS exposure
      and current ETS exposure were associated with increased prevalence of persistent
      cough, persistent phlegm, wheeze and wheeze without asthma. Among boys, ETS
      exposure was associated with more respiratory symptoms and diseases than in
      girls. ETS exposure during pregnancy was associated with asthma symptom [odds
      ratio (OR), 3.00; 95% confidence interval (CI): 1.28-7.03], current asthma (OR,
      3.38; 95% CI: 1.25-9.14), persistent cough (OR, 1.64; 95% CI: 1.13-2.37),
      persistent phlegm (OR, 1.74; 95% CI: 1.01-3.01), wheeze (OR, 1.75; 95% CI: 1.15
      2.68), and wheeze without asthma (OR, 1.46; 95% CI: 1.01-2.37) only among boys.
      In boys, the adjusted ORs for increased risk of asthma symptom and current asthma
      for household exposures (> or =10 cigarettes smoked per day vs. none smoked)
      during workday were 2.04 (95% CI: 1.01-3.89) and 2.76 (95% CI: 1.06-9.58),
      respectively. We conclude that ETS exposure increases the occurrence of
      respiratory symptoms and diseases during childhood. Boys may be more susceptible
      to ETS than girls. PRACTICAL IMPLICATIONS: Environmental tobacco smoke (ETS) is a
      highly prevalent respiratory irritant. In agreement with previous cross-sectional
      studies, our study indicates that exposure to ETS may increase the occurrence of
      respiratory symptoms and diseases in children, and the association of ETS
      exposure and respiratory health of children increased in strength with number of
      cigarettes smoked inside the house per day during workday and day-off. Boys may
      be more susceptible to ETS than girls. These findings support the view that
      measures should be taken to reduce ETS exposure for children.

PMID- 18045274
TI  - Stem cell transplantation in primary immunodeficiency disease patients.
AB  - BACKGROUND: Primary immunodeficiency diseases (PID) are rare but have a high
      associated risk of death from overwhelming infection in early childhood. Stem
      cell transplantation (SCT) can be curative for PID, but standardized protocols
      for each disease have not yet been established. METHODS: Between May 1995 and May
      2005, nine patients diagnosed with a PID received SCT at the Department of
      Pediatrics, Hokkaido University Hospital. The median age of the patients (eight
      boys and one girl) was 1.0 year (range: 6 months-4 years). Five patients had
      Wiskott-Aldrich syndrome (WAS), three had severe combined immunodeficiency
      (SCID), and one had X-linked hyper-IgM syndrome (X-HIGM). Four patients received
      bone marrow transplantation (BMT), and five received cord blood stem cell
      transplantation (CBSCT). All patients, including those with SCID, received a
      conditioning regimen: six (WAS and X-HIGM) received a myeloablative conditioning
      regimen, and three (SCID) received a reduced-intensity conditioning regimen.
      RESULTS: All the patients are alive and have stable, complete chimerism, based on
      a median follow-up period of 4 years. Moreover, all patients have good immune
      reconstitution, and none required immunoglobulin replacement therapy. Two
      patients had significant acute graft-versus-host disease (GVHD), and three
      patients had chronic GVHD. Four of the nine patients developed cytomegalovirus
      (CMV) infection after SCT. CONCLUSION: The transplantation procedures appear to
      have provided a permanent cure in nine PID patients. Early diagnosis and prompt
      performance of SCT with an optimal donor and conditioning regimen contributed to
      the favorable outcomes.

PMID- 18045275
TI  - Home mechanical ventilation in children: retrospective survey of a pediatric
      population.
AB  - BACKGROUND: Home care support is beneficial for children needing mechanical
      ventilation, when clinically stable. METHODS: A retrospective analysis was
      carried out of the long-term home ventilation management of a pediatric
      population with chronic respiratory failure composed of 20 ventilator-dependent
      children categorized according to age, diagnosis and ventilation support. Age
      groups consisted of 10% under 1 year, 30% between 2 and 5 years, 30% between 6
      and 12 years, and 30% older than 12 years. Diagnostic categories included
      myopathic disorder, n = 5; congenital central hypoventilation syndrome, n = 6;
      chest wall disorder, n = 5; cystic fibrosis, n = 1; pulmonary hypertension, n =
      1; and diaphragmatic paralysis, n = 2. RESULTS: Sixty-five percent were
      ventilated using non-invasive mode (NIMV): eight with nasal mask, five with full
      face mask, and two children in NIMV also used negative pressure mode; 35% were
      ventilated using tracheostomy, one of them also used a diaphragmatic pacer.
      Seventy percent needed nocturnal ventilatory support, (20% 12-18 h, 10% full
      day). A total of 18 children were included in the home care and follow-up
      program. Two children died: one because of worsening of his chronic disease and
      one because of septic shock. CONCLUSION: Although home care ventilation is not
      yet widely diffused, it represents a valid alternative to long hospitalization
      for children with stable chronic respiratory failure.

PMID- 18045276
TI  - Predictive factors for organic central precocious puberty and utility of
      simplified gonadotropin-releasing hormone tests.
AB  - BACKGROUND: The aim of the present study was to determine whether the clinical
      presentation of patients with central precocious puberty (CPP) permits
      differentiation between idiopathic and organic forms, and to examine whether
      luteinizing hormone (LH) determination in single blood sample after gonadotropin
      releasing hormone (GnRH) administration is sufficient to diagnose CPP. METHODS:
      Potential clinical and laboratory predictors for the presence of central nervous
      system (CNS) abnormalities were assessed. Sensitivities and specificities of LH
      and follicle-stimulating hormone (FSH) levels at 0, 15, 30, 60, 90 and 120 min
      were compared after GnRH stimulation. RESULTS: In 45 girls with signs of breast
      development, 26 were diagnosed as having CPP. The age of onset in patients with
      organic CPP was 4.75 +/- 2.01 years (range 1.2-7.1 years, median 5.0 years),
      whereas the age in patients with idiopathic CPP was 7.09 +/- 0.87 years (range
      5.0-7.9 years, median 7.0 years). This parameter is the only one showing
      statistical significance. In addition, the specimen at 30 min after GnRH
      stimulation yielded highest sensitivity for the diagnosis of CPP. CONCLUSIONS:
      The earlier the onset of disease, the higher the possibility of presence of CNS
      lesion. According to the mean GnRH-stimulated LH levels and sensitivity at each
      time, a single blood sample obtained for LH determined after GnRH administration
      at 30 min can be used to diagnose CPP.

PMID- 18045277
TI  - Epidemiological study of sleep characteristics in Chinese children 1-23 months of
      age.
AB  - BACKGROUND: Sleep plays a critical role in normal development and the effects of
      culture upon sleep are especially important in young children. The purpose of the
      present paper was to determine the sleep times and the prevalence of sleep
      problems and co-sleeping in children from Shanghai. METHODS: A cross-sectional
      design incorporating parental self-report was used to investigate the sleep
      related habits of 1129 children, 1-23 months of age, randomly selected from the
      five districts of Shanghai, China. RESULTS: The total sleep time (TST) of Chinese
      young children was less than that reported in Western populations, and the
      prevalence of sleep problems (65.97%) was higher than that for Western children.
      The sleep problems of children were significantly related to perinatal factors
      and certain behavior problems. The rate of bed sharing did not differ between
      boys and girls but significantly increased with age from 44.07% in 1-month-olds
      to 71.51% in 23-month-olds. CONCLUSIONS: Sleep problems that cross cultures
      result from a variety of behavioral and health problems. Nevertheless, it is
      speculated that reduced TST in Chinese children may be related to factors unique
      to China, such as co-sleeping and child-rearing practices.

PMID- 18045278
TI  - Immunoadsorbent apheresis eliminates pathogenic IgG in childhood lupus nephritis.
AB  - BACKGROUND: It is suggested that the highly cation-charged fraction of the IgG
      and IgG3 subclasses may play a pathogenic role in lupus nephritis. In contrast,
      immunoadsorbent therapy using a sodium dextransulfate fixed cellulose gel column
      low invasive selective immunoadsorbent apheresis therapy (SDSC-IAT) has been
      applied to lupus nephritis with favorable results. However, elimination using
      pathogenic IgG by SDSC-IAT has never been investigated. METHOD: Two patients with
      diffuse proliferative lupus nephritis were treated using SDSC-IAT concomitant
      with immunosuppressive therapy. The eluates from the SDSC, and the patients'
      serum obtained before and just after SDSC-IAT were subjected to an IgG charge
      analysis using isoelectric focusing and immunoblotting, and also to laser
      nephelometry assay, which is used for measuring IgG subclass concentration.
      Indirect immunofluorescence staining was performed to detect IgG subclass
      deposition in the glomerulus. RESULTS: Both of the patients had an immediate
      decrease in anti-double-strand DNA antibody and in the circulating immune complex
      with a following clinical improvement. Repeated biopsies demonstrated improvement
      of glomerular lesions with a marked reduction of IgG and C3 deposition. The IgG
      of the SDSC eluates consisted of highly cation charged (isoelectric points: 9-10)
      fractions. In addition, IgG3 was specifically removed from the patients' serum
      using an SDSC among the IgG subclasses. The subclass of deposited IgG in the
      glomeruli showed IgG3 predominance. CONCLUSION: SDSC-IAT specifically removed the
      highly cation charged fractions of IgG and IgG3 from the patients' serum and the
      elimination of these fractions may have resulted in clinical improvement.

PMID- 18045279
TI  - Thyroid function and volume in epileptic children using carbamazepine,
      oxcarbazepine and valproate.
AB  - BACKGROUND: The aim of the present study was to investigate the effects of
      carbamazepine (CBZ), oxcarbazepine (OXC), and valproic acid (VPA) on thyroid
      function and volume in epileptic children. METHODS: Fifty-three epileptic
      children (age, 3-17 years) treated with OXC (n = 10), CBZ (n = 12), or VPA (n =
      31) at least for 1 year were evaluated in terms of thyroid hormones, thyroid
      stimulating hormone (TSH) levels, response to thyrotropin-releasing hormone (TRH)
      stimulation test, and thyroid volumes. RESULTS: The patients in the OXC and CBZ
      groups had similar total thyroxin (TT4) and free T4 (fT4) median levels that were
      significantly lower than those of the VPA group (P < 0.016). Total tri
      iodothyrosin median levels were lower in the CBZ group compared to the VPA group
      (P < 0.016). Basal TSH levels and thyroid volumes were similar in all groups (P >
      0.016). One child from the OXC group (10%), one from the CBZ group (%8.3), and
      six from the VPA group (19.3%) had hypothyroidic status according to the TRH
      stimulation test. No statistically significant correlations were found between
      thyroid gland volume and thyroid function variables and between anti-epileptic
      drug receiving time and thyroid function or thyroid volume, respectively, in any
      of the groups (P > 0.05). CONCLUSIONS: Thyroid function should be evaluated
      periodically in children using CBZ, OXC or VPA. The children taking VPA seems to
      be at greater risk compared to children onr CBZ or OXC therapy. Except for the
      basal TSH values in the VPA group, the parameters predictive for the subclinical
      hypothyroid status remain to be evaluated in further studies.

PMID- 18045280
TI  - Correlation between white blood cell count and metabolic syndrome in adolescence.
AB  - BACKGROUND: Metabolic syndrome (MetS) is associated with increased risk for
      diabetes and coronary heart disease. Data suggest that MetS starts even in
      children. Thus, it is important to understand the role of MetS and the risks
      related to it. Furthermore, white blood cell count (WBCC) is available in routine
      examination and it has been proved to be related to risks of MetS. METHODS: A
      total of 1657 subjects aged 14-19 years were enrolled, with normal WBCC (< or =10
      x 10(9) cells/L). The subjects were divided into four quartiles according to WBCC
      (WBCC1-4, from the lowest to highest WBCC) in both genders. RESULTS: The female
      subjects had significantly lower systolic blood pressure, fasting plasma glucose
      (FPG), triglyceride (TG), body mass index (BMI) and higher high-density
      lipoprotein-cholesterol (HDL-C) than the male subjects. When comparing the risks
      of the quartiles of WBCC, WBCC4 had significant higher BMI than WBCC1 and WBCC2
      in both genders; and lower HDL-C than WBCC3 in male subjects. On multiple
      regression WBCC was positively related with BMI and TG and negatively related to
      HDL-C in male subjects. In female subjects only BMI was positively correlated
      with WBCC. Subjects with MetS did not have significant higher WBCC than those
      without MetS. CONCLUSIONS: In adolescents with normal WBCC, BMI is significantly
      related to the levels of WBCC and is the earliest component of MetS to be noted
      in adolescents. Elevated TG and decreased HDL-C could also be important markers
      for future risk factors only in male subjects.

PMID- 18045281
TI  - Are laboratory tests necessary in making the diagnosis of limb pains typical for
      growing pains in children?
AB  - BACKGROUND: The present study was conducted to determine if performing laboratory
      tests are necessary to exclude other possible diagnoses in a child with limb
      pains typical for growing pains according to history and physical examination.
      METHODS: A matched case-control study was carried out on children with limb pains
      who attended the Motahary clinic, Shiraz, Iran, in a 2 year period. The inclusion
      criteria were limb pains, which were recurrent and lasted for more than 3 months.
      The exclusion criteria were any abnormal systemic symptoms and signs, localizing
      signs, joint involvement; and limp or limitation of activity. The controls were
      clinically normal children matched for age and sex. Laboratory tests including
      complete blood count, erythrocyte sedimentation rate, serum calcium, phosphorus,
      alkaline phosphatase and rheumatoid factor were done for all patients and
      controls. RESULTS: In total, 100 patients and 150 controls were included in the
      study. There were no significant differences between the patients and controls
      with regard to all of the measured laboratory tests. CONCLUSION: Growing pain is
      a clinical diagnosis and if precise inclusion and exclusion criteria in history
      and physical examination are considered, there will be no need for laboratory
      tests in order to make a diagnosis.

PMID- 18045282
TI  - (13)C-phenylalanine breath test correlates with liver fibrosis in postoperative
      biliary atresia.
AB  - BACKGROUND: Values derived from the (13)C-phenylalanine breath test (PBT) may
      serve as an index for liver fibrosis and clinically predictive readings for liver
      diseases in adults. In the present study the PBT was conducted in postoperative
      biliary atresia (BA) children to evaluate phenylalanine metabolism in the liver,
      and the results based on biochemical data, especially the index on liver
      fibrosis, were compared with PBT findings. METHODS: Hepatofunctional evaluations
      were conducted in 10 postoperative BA children with moderate (group B; n = 4) and
      severe (group A; n = 6) liver dysfunction, and the PBT results were compared with
      those of 13 normal healthy children (group C). Subjects were orally given single
      bolus (13)C-phenylalanine at 3.5 mg/kg (maximum dosing: 100 mg) in the morning.
      Time-related exhaled gas was periodically collected until 120 min after dosing.
      The (13)CO(2) levels were monitored with gas chromatography-mass spectrometry
      before and after administration, and the (13)C excretion rate, (13)C cumulative
      excretion and time of maximum (13)C excretion rate were monitored accordingly.
      RESULTS: Total bile acid, hyaluronic acid, type IV collagen 7S, total bilirubin
      or albumin and the PBT findings were significantly correlated. The PBT findings
      in group A were significantly lower those of group B, indicating that
      phenylalanine metabolism was markedly attenuated in the former. CONCLUSION: The
      PBT values correlated well with liver fibrosis in postoperative BA children.
      Because PBT is a non-invasive approach, results from this method may serve as a
      useful and reliable index for post-surgical monitoring of children operated on
      for liver fibrosis.

PMID- 18045283
TI  - Effect of zinc sulfate on common cold in children: randomized, double blind
      study.
AB  - BACKGROUND: The aim of the present randomized, double-blind, placebo-controlled
      study was to determine the efficacy of zinc sulfate on the duration and severity
      of common cold in children. METHODS: Children presenting at least two of 10
      symptoms of common cold within the 24-48 h of the onset of illness were eligible
      for the study. Children were randomized to receive either oral zinc containing
      zinc sulfate or placebo. A diary was completed to record symptoms and adverse
      effects. Symptoms were scored as absent (0), mild (1), moderate (2), or severe
      (3). RESULTS: One hundred and fifty children participated in the study, and 120
      children were included in the final analysis. The median duration of all cold
      symptoms was 6 days (P = 0.20), and the median duration of nasal symptoms was 5
      days in both groups (P = 0.09). However, total symptom severity scores were
      significantly lower in the zinc group, starting from the second day of the study.
      The lower scores in the zinc group were largely due to improvement of nasal
      symptom scores. Adverse effects were similar in both groups. CONCLUSION: Zinc
      sulfate had no effect on the duration of cold symptoms. However, it appears to be
      effective in reducing the severity of the cold symptoms in healthy children.

PMID- 18045284
TI  - Therapeutic efficacy of sequential and simultaneous treatments with interferon
      alpha and lamivudine in children with chronic hepatitis B.
AB  - BACKGROUND: Interferon (IFN)-alpha and lamivudine (LAM), a nucleoside analog, are
      frequently used drugs for the treatment of chronic hepatitis B (CHB), and their
      combined therapy has been shown to be effective. The purpose of the present study
      was to examine the therapeutic efficacy of sequential and simultaneous
      combination therapies of IFN-alpha and LAM in children with CHB. METHODS: A total
      of 45 children with CHB, whose antibody status was positive for hepatitis B
      surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), and HBV-DNA at
      least for 6 months; who had alanine aminotransferase (ALT) levels 1.5-fold higher
      than normal and hepatic activity index scores higher than 6, were allocated to
      two groups. The first group included 24 children who were given standard dose IFN
      alpha (5 MU/m(2) s.c., thrice weekly) for 6 months, followed by LAM (4 mg/kg per
      day per oral, maximum 100 mg/day) for an additional 6 months (sequential therapy
      group). The second group included 21 children who were given IFN-alpha and LAM
      therapy simultaneously for 6 months and who continued with LAM alone for another
      6 months (simultaneous therapy group). Partial response was defined as
      normalization of ALT and eradication of HBV-DNA. Complete response was defined as
      normalization of ALT, eradication of HBV-DNA and e seroconversion. Non-responders
      were defined as having positive HBV-DNA and abnormal ALT levels. Sustained
      response was defined as absence of HBsAg and presence of hepatitis B surface
      antibody (anti-HBs). RESULTS: The mean age of the sequential therapy group was
      12.7 +/- 4.1 years, and 16 (66.7%) of the patients were male. The mean age of the
      simultaneous therapy group was 14.8 +/- 4.6 years, and 15 (71.4%) were male. In
      the first group, 13 patients (54.2%) were non-responders; partial response was
      observed in five patients (20.8%), and complete response was seen in six patients
      (25%). Despite the occurrence of e seroconversion, normalization of ALT was not
      achieved in one case. In the second group, which consisted of 21 patients, 11
      subjects (52.4%) were non-responders; partial response was observed in one case
      (4.8%), and complete response was seen in seven (33.3%). Sustained response was
      found in two patients (9.5%). There were no significant differences between the
      groups (P > 0.05). CONCLUSION: When the therapeutic efficiency of two different
      treatment regimens applied for 1 year was evaluated in childhood CHB therapy, it
      was remarkable that there was a sustained response and a higher complete response
      in group 2, although there was no considerable difference between the therapy
      results of both groups.

PMID- 18045285
TI  - Factors affecting oral health habits among children with cerebral palsy: pilot
      study.
AB  - BACKGROUND: The aim of the present study was to investigate the factors affecting
      the oral health habits of children with spastic-type cerebral palsy (CP).
      METHODS: A total of 35 children with CP and their mothers were randomly selected
      for this cross-sectional study. Data regarding their sociodemographic
      characteristics and their oral health habits were collected during face-to-face
      interviews. RESULTS: Logistic regression analysis indicated that mothers'
      irregular brushing habits were a risk factor for their children's lack of regular
      brushing habits (odds ratio: 6.4, P = 0.048). Additionally, a significant
      association was observed between the mother's length of time between dental
      visits and the length of time between children's dental visits (R(2)= 0.11, P =
      0.046). CONCLUSIONS: Mothers' oral health habits, including brushing habits and
      frequency of dental visits, are important factors in promoting healthy and
      beneficial oral health habits in children with CP in Turkey.

PMID- 18045286
TI  - Association of Helicobacter pylori infection with gastroduodenal disease,
      epidemiologic factors and iron-deficiency anemia in Turkish children undergoing
      endoscopy, and impact on growth.
AB  - BACKGROUND: The purpose of the present paper was to investigate the relationship
      between Helicobacter pylori infection and clinical symptomatology, breast-feeding
      and socioeconomic level. The relationship between H. pylori and iron-deficiency
      anemia (IDA) and the effect of H. pylori infection on growth were also
      investigated. METHODS: The subjects consisted of 70 patients aged 4-16 years who
      underwent upper gastrointestinal endoscopy for recurrent abdominal pain, nausea,
      vomiting, and dyspeptic complaints during a 2 year period. Patients were divided
      into two groups according to presence of histological evidence of H. pylori
      infection (group 1, H. pylori positive; group 2, H. pylori negative) and groups
      were compared with respect to epidemiologic characteristics, gastrointestinal
      complaints, height and weight SD scores and IDA. RESULTS: Thirty-five (50%) of
      the 70 patients participating in the study were H. pylori positive. The mean age
      of group 1 was significantly higher than that of group 2. There were similar
      characteristics and symptomatology between groups. The majority of the patients
      in group 1 belonged to low socioeconomic class (class I and II; P < 0.05). The
      number of the patients exclusively breast-fed for > or =4 months was
      significantly higher in group 2 than in group 1. Gastritis was significantly more
      frequent in group 1. Mean hemoglobin, serum Fe and ferritin levels were 11.6 +/-
      1.7 g/dL, 45.0 +/- 23.2 microg/dL and 11.9 +/- 8.4 microg/dL, respectively, for
      group 1 and 12.2 +/- 0.7 g/dL, 79.3 +/- 26.4 microg/dL and 42.1 +/- 31.8
      microg/dL, respectively, for group 2. The mean serum Fe and ferritin levels of
      group 2 were significantly higher than those of group 1. IDA was observed in 20
      (57.1%) and six (17.1%) patients in groups 1 and 2, respectively. IDA was
      significantly more frequent in group 1. Helicobacter pylori infection was found
      to be the only variable that had significant effect on IDA. Mean SD height and
      weight for group 1 were lower than those of the group 2. When the patients were
      evaluated in four groups according to H. pylori and IDA status, mean height SD
      score of patients with both H. pylori infection and IDA was significantly lower
      than that of the patients negative for H. pylori and IDA concomitantly.
      CONCLUSION: Low socioeconomic status seems to be an important risk factor for H.
      pylori infection. Exclusive breast-feeding at least for 4 months can have a
      protective role against H. pylori infection. Increased frequency of growth
      retardation and IDA in H. pylori-infected patients in the present study supports
      similar findings in the literature, although there is still need for detailed
      studies to clarify the causative mechanisms.

PMID- 18045287
TI  - Quantitative measurements of Hemophilus influenzae type b capsular polysaccharide
      antibodies in Japanese children.
AB  - BACKGROUND: Hemophilus influenzae type b (Hib) infection has a high morbidity and
      mortality rate in children. The frequency of natural immunity against Hib in
      Japanese children is not known, and Hib vaccine has not yet been introduced in
      Japan. METHODS: Anti-capsular polysaccharide-specific IgG (anti-CP) antibody
      titers were examined in serum samples from 100 children and 107 young adults who
      were not vaccinated against Hib, in serum samples from eight patients with Hib
      systemic infection and in 10 commercially available human immune globulin
      preparations on enzyme-linked immunosorbent assay. RESULTS: A total of 44%
      (44/100) of Japanese children and all patients with Hib systemic infection in the
      acute phase did not have the minimum protective level of anti-CP antibodies
      (>0.15 microg/mL). The rate of natural Hib immunity was lowest in children under
      1 year of age and gradually increased with age. Only 3.74% (4/107) of Japanese
      young adults did not have the minimum protective level of anti-CP antibodies.
      Analysis of 10 commercially available human immune globulin preparations
      indicated an average level of 28.25 microg anti-CP antibody/mL immune globulin
      (range 14.96-44.17 microg/mL). CONCLUSIONS: Approximately half of Japanese
      children are not protected against Hib infection. Therefore, Hib vaccine should
      immediately be included as part of the routine immunization program in Japan. It
      was also found that all tested commercially available immune globulin
      preparations had high anti-CP titers. Well-controlled clinical trials of i.v.
      immune globulin administration for prevention and treatment of Hib systemic
      infection are needed in Japan.

PMID- 18045288
TI  - Utility of diagnostic tests for detection of Helicobacter pylori in children in
      northeastern Mexico.
AB  - BACKGROUND: The presence of Helicobacter pylori in pediatric population has been
      associated with recurrent abdominal pain (RAP), although this association is
      unclear. One of the major problems in studying the role of H. pylori in RAP is
      that methods used to detect the bacteria in children have poor sensitivity and
      specificity. The aims of the present study were to determine the prevalence of H.
      pylori in pediatric patients with RAP in northeastern Mexico and to assess the
      diagnostic utility of invasive tests and serology in this population. METHODS: A
      total of 40 patients (mean age, 7.9 years; range 2-16 years; F: M, 0.81), who
      underwent an endoscopy procedure for RAP, were studied. The presence of H. pylori
      was assessed using invasive diagnostic tests (culture, rapid urease test,
      polymerase chain reaction and histology) and one non-invasive test: determination
      of IgG antibodies. The prevalence of H. pylori in the present group and the
      diagnostic utility for each test were evaluated. RESULTS: The prevalence of H.
      pylori in the present pediatric group with RAP was 12.5-42.5% depending on the
      criteria of positivity used. The non-invasive methods (serology) had acceptable
      values in sensitivity and specificity in comparison with invasive tests.
      CONCLUSIONS: This is the first report on prevalence of H. pylori in pediatric
      patients with RAP from the northeastern region of Mexico. The prevalence of H.
      pylori was low compared with the adult population in the same geographic region.
      Serology had the best diagnostic utility.

PMID- 18045289
TI  - Nosocomial Gram-positive bacterial infections in children: results of a 7 year
      study.
AB  - BACKGROUND: The aim of the present paper was to determine the rate of culture
      proven nosocomial infections and evaluate the episodes of nosocomial Gram
      positive (GP) bacterial infections in pediatric patients. METHODS: The data of
      children with positive culture, who were diagnosed as having nosocomial infection
      on the Centers for Disease Control and Prevention criteria, were examined and
      only the patients with nosocomial GP bacterial infections were included in the
      study. RESULTS: Between January 1997 and January 2004 a total of 836 episodes of
      nosocomial GP bacterial infections were observed. The most frequently seen
      nosocomial GP bacterial infections were primary bloodstream infections (BSI;
      43%), ventriculoperitoneal shunt infections (18%), and nosocomial pneumonias
      (11%). Coagulase-negative staphylococci (CONS; 46%) were the most common
      nosocomial GP bacteria isolated, followed by Staphylococcus aureus (33%).
      Methicillin resistance rates for CONS and S. aureus were 85% and 25.2%;
      respectively. The mortality rate was 4% of all children with nosocomial GP
      bacterial infections in the present study. CONCLUSION: In the present patients
      primary BSI were the most common nosocomial GP bacterial infections and CONS were
      the most frequent GP pathogen isolated. Antimicrobial resistance in GP isolates
      is an increasing problem.

PMID- 18045290
TI  - Post-mortem analysis for two prevalent beta-oxidation mutations in sudden infant
      death.
AB  - BACKGROUND: Fatty acid oxidation disorders may cause sudden and unexpected infant
      death and are associated with the histological hallmark of hepatic steatosis. The
      goal of the present study was to assess the value of post-mortem molecular
      analysis for medium-chain acyl-coenzyme A dehydrogenase (MCAD) and mitochondrial
      trifunctional protein (MTP) defects in unexplained sudden infant death (SID)
      associated with fatty infiltration of the liver. MCAD catalyzes the first step of
      medium-chain fatty acid oxidation while MTP catalyzes the last three steps of
      long-chain fatty acid oxidation. METHODS: In a retrospective study, 220
      consecutive cases of sudden and unexplained infant death certified by medical
      examiners at Wake Forest University Medical Center were assessed for hepatic
      steatosis. Subjects with evidence of hepatic steatosis were screened for
      mutations in MCAD and MTPalpha-subunit using DNA isolated from paraffin-embedded
      liver tissue, single-strand conformation variance, and nucleotide sequence
      analyses. RESULTS: Sixteen cases (7.3%) were associated with diffuse micro
      vesicular or mixed micro- and macro-vesicular hepatic steatosis. Two of these 16
      cases (12.5%) had disease-causing mutations. One was homozygous for the prevalent
      MCAD A985G mutation. The second was a compound heterozygous for the prevalent MTP
      G1528C mutation and a novel 1 bp deletion in exon 18 of the MTPalpha-subunit
      gene. CONCLUSIONS: A significant proportion (7.3%) of SID is associated with
      hepatic steatosis. The present data support post-mortem molecular analysis for
      the MCAD A985G and MTP G1528C prevalent mutations in cases of sudden and
      unexplained infant death associated with hepatic steatosis.

PMID- 18045291
TI  - Elevation of serum stem-cell factor in postoperative biliary atresia.
AB  - BACKGROUND: Biliary atresia (BA) is one of the most common causes of neonatal
      cholestasis. Stem-cell factor (SCF) has been implicated in the development of
      fibrosis in various diseases. The objective of the present study was to examine
      the significant role of SCF in BA. METHODS: Fifty-seven pediatric patients with
      BA after Kasai operation and 30 healthy children were recruited. The mean ages of
      BA patients and controls were 6.1 +/- 0.6 years and 6.1 +/- 0.7 years,
      respectively. The patients were categorized into two groups according to their
      serum levels of total bilirubin (TBil < 2 mg/dL, no jaundice vs TBil > or = 2
      mg/dL, persistent jaundice) and alanine aminotransferase (ALT < 100 vs ALT > or =
      100 U/L). The serum SCF levels were determined on commercially available enzyme
      linked immunosorbent assay. RESULTS: The mean serum SCF level of the BA children
      was higher than that of normal controls (748.3 +/- 17.9 pg/mL vs 582.2 +/- 17.3
      pg/mL; P < 0.001). Subsequent analysis demonstrated that the BA patients with
      serum ALT > or = 100 U/L had significantly greater levels of serum SCF compared
      to those with serum ALT < 100 U/L (796.5 +/- 22.6 pg/mL vs 694.7 +/- 25.0 pg/mL,
      respectively; P = 0.002). In addition, serum SCF levels were significantly
      elevated in the patients with portal hypertension (PH) compared with those
      without PH (810.0 +/- 18.8 pg/mL vs 634.1 +/- 20.1 pg/mL, P < 0.001). CONCLUSION:
      The current study showed that BA patients had higher serum SCF levels compared
      with controls. The significant elevation in SCF levels is associated with the
      presence of PH and the degree of hepatic injury. These findings suggest that SCF
      may play a part in the pathogenesis of hepatic fibrosis in BA patients after
      Kasai procedure.

PMID- 18045292
TI  - Human milk reduces the risk of retinal detachment in extremely low-birthweight
      infants.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is a major cause of blindness in
      children. Because the use of oxygen is a known risk factor for development of
      ROP, supplemental oxygen is used carefully. However, it does not necessarily
      reduce the morbidity of ROP-induced blindness. The aim of the present study was
      to identify the possible risk factors for progression to retinal detachment, a
      most relevant cause of visual impairment, in extremely low-birthweight infants
      (ELBWI). METHODS: The medical records of the 42 ELBWI who were admitted to the
      neonatal intensive care unit in Asahikawa Kosei Hospital from April 1999 to March
      2004 were retrospectively reviewed. Seven infants (16.7% of the ELBWI) developed
      retinal detachment and two of them became blind. Perinatal and postnatal
      variables in these infants with retinal detachment were compared with those in
      infants without retinal detachment. RESULTS: A striking difference in the daily
      intake of human milk was found between the infants with or without retinal
      detachment when their gestational ages at birth were matched. The infants without
      retinal detachment were fed more human milk (67-83% volume of total nutritional
      intake) as compared to those with retinal detachment (24-38% volume of total
      nutritional intake) at a specific postnatal period, 5-7 weeks postnatal age.
      CONCLUSIONS: Human milk may contain some beneficial factors to reduce the
      severity of ROP. Identifying these factors in human milk may contribute to
      development of a strategy to rescue premature infants from blindness.

PMID- 18045293
TI  - Impaired transient elevation of blood hemoglobin in response to acute hypoxia in
      neonates with asplenia.
AB  - BACKGROUND: It has been shown that acute hypoxia induces the transient elevation
      of blood hemoglobin concentration ([Hb]) as a consequence of sympathetic-mediated
      splenic contraction to maintain the supply of oxygen, and splenectomy abolishes
      this phenomenon. The purpose of the present paper was to determine,
      retrospectively, whether the ability of transient elevation of [Hb] against acute
      hypoxia would be impaired in neonates with asplenia. METHOD: Eleven neonates who
      underwent surgery from 1998 to 2003 were enrolled in this retrospective study.
      They were divided into two groups: (i) five patients with asplenia syndrome with
      cyanotic congenital heart disease (asplenia group); and (ii) six patients with
      hypoplastic left heart syndrome who needed nitrogen gas inhalation therapy (HLHS
      group). In the asplenia group simultaneous data of arterial oxygen saturation
      (Sao(2)) and [Hb] were obtained before and after the temporary unexpected
      decrease of percutaneous arterial oxygen saturation. In the HLHS group they were
      obtained before and after nitrogen gas administration therapy. The arterial
      oxygen content (Cao(2)) changes and the ratio of Cao(2) change (Cao(2) after
      hypoxia divided by Cao(2) before hypoxia) were also calculated. RESULTS: In the
      asplenia group [Hb] was unchanged (12.9 +/- 1.6 g/dL to 12.8 +/- 1.4, n.s.) and
      Cao(2) was decreased (14.5 +/- 1.6 mL/dL to 11.9 +/- 1.1, P = 0.018). In the HLHS
      group [Hb] was increased (14.6 +/- 1.3 g/dL to 15.4 +/- 1.5, P = 0.028), but
      Cao(2) was changed (18.2 +/- 2.2 mL/dL to 16.7 +/- 3.0, P = 0.043). The ratio of
      Cao(2) change for the HLHS group was significantly different from that of the
      asplenia group (0.92 +/- 0.10, 0.83 +/- 0.10, respectively, P = 0.02).
      CONCLUSIONS: Patients with asplenia syndrome have some disadvantage regarding
      this protective mechanism against acute hypoxia.

PMID- 18045294
TI  - Neonatal subgaleal hemorrhage: clinical presentation, treatment, and predictors
      of poor prognosis.
AB  - BACKGROUND: Neonatal subgaleal hemorrhage (SGH) is a rare but potentially lethal
      medical emergency. The objective of the present retrospective study was to
      clarify the clinical presentation, management, and factors associated with
      morbidity and mortality. METHODS: The records of all newborns from January 1995
      to December 2004 were reviewed for evidence of SGH, based on the presence of a
      fluctuating hemorrhagic mass that crossed suture lines and extended toward the
      neck. Characteristics were compared between those with a poor or a good outcome.
      RESULTS: Forty-two newborns with SGH were identified, 77% having had an
      instrumental delivery. The incidence was 0.6/1000 deliveries and 4.6/1000 vacuum
      assisted deliveries. Thirteen patients (31%) had a poor outcome (five died, four
      had epilepsy, three with severe auditory dysfunction, two with cerebral palsy,
      and one with renal vein thrombosis). The group with the poor outcome had
      significantly more patients who had been transferred from other hospitals (P <
      0.001). Those with a poor outcome had significantly more hypotension (P < 0.001)
      and seizures (P < 0.05). Laboratory findings associated with a poor outcome
      included anemia, coagulopathy, metabolic acidosis, and renal impairment. Other
      predictors of a poor prognosis included skull bone fracture, the need for
      pressors, blood transfusion, ventilator support, intensive care unit admission,
      and a longer hospital stay. CONCLUSIONS: SGH may be associated with serious
      complications and death. The condition must be recognized promptly and monitored
      closely. Those with poor prognostic factors should be referred for intensive
      care, treated aggressively, and followed in the long term.

PMID- 18045295
TI  - Hemodynamic features of congenital aortic valve stenosis with patent ductus
      arteriosus in children.
AB  - BACKGROUND: The aim of the present paper was to investigate the hemodynamic
      features of congenital aortic valvar stenosis (AS) associated with patent ductus
      arteriosus (PDA), and to develop information to guide management of AS with
      coexistent PDA. METHODS: Hemodynamic measurements were performed in eight of 11
      patients with AS before and following transcatheter closure of a PDA. Doppler
      cardiac ultrasound and chest X-rays were performed during follow up. RESULTS: In
      each of the 11 patients, aortic valve gradient was markedly reduced following
      transcatheter ductal closure. In only one of them was balloon aortic
      valvuloplasty necessary. CONCLUSION: Aortic valve gradient was markedly
      overestimated before closure of PDA. The significance of this finding has focused
      on selecting appropriate management so that a PDA is not overlooked when
      intervention for AS is performed.

PMID- 18045296
TI  - Tissue Doppler echocardiographic assessment of cardiac function in children with
      bronchial asthma.
AB  - BACKGROUND: The aim of the present study was to evaluate the role of tissue
      Doppler echocardiography in assessment of ventricular function in pediatric
      patients with bronchial asthma (BA). PATIENTS AND METHODS: Fifty-one pediatric
      patients with BA and 30 age- and sex-matched healthy subjects were studied. BA
      patients were divided into two groups: mild BA (n = 33) and moderate to severe BA
      (n = 18). All subjects were examined on conventional and tissue Doppler
      echocardiography, and 44 patients had pulmonary function tests on spirometry
      within 1 week of echocardiographic examination. RESULTS: Conventional
      echocardiographic parameters were all similar in mild asthmatic patients and
      control subjects. Tricuspid E velocity, E/A ratio and isovolumetric relaxation
      time (IVRT) in moderate and severe cases differed significantly from mild cases
      and control subjects. E', A', E'/A' ratio and IVRT of the lateral tricuspid
      annulus, and IVRT of the medial and lateral mitral annuli were different between
      mild cases and control subjects. E' velocity and IVRT of the lateral tricuspid
      annulus and IVRT of the medial and lateral mitral annuli were also different
      between mild cases and moderate to severe cases. Pulmonary function tests
      correlated well with E', E'/A' and IVRT of lateral tricuspid annulus. CONCLUSION:
      Patients with BA have subclinical right ventricular diastolic dysfunction even in
      the early stages. The severity of the functional impairment is parallel with the
      severity of the disease. Tissue Doppler echocardiography has a greater predictive
      value than conventional imaging, and is useful for evaluating ventricular
      function in patients with BA.

PMID- 18045297
TI  - Suppression of plasma matrix metalloproteinase-9 following montelukast treatment
      in childhood asthma.
AB  - BACKGROUND: Montelukast and ketotifen are commonly prescribed anti-inflammatory
      medications used in the treatment of childhood asthma. METHODS: To investigate
      the modulation effect of montelukast and ketotifen, the levels of exhaled nitric
      oxide (eNO) and plasma matrix metalloproteinase-9 (MMP-9) were analyzed in a
      group of 30 children with mild persistent asthma. RESULTS: Patients on
      montelukast therapy for 8 weeks had significantly decreased levels of eNO and
      plasma MMP-9, which were associated with improved symptoms and enhanced peak
      expiratory flow but not significantly associated with increased level of tissue
      inhibitor metalloproteinase-1 (TIMP-1). In contrast, treatment with ketotifen
      produced no significant changes in these parameters until 4-6 weeks into the
      therapy and no effect on plasma MMP-9. CONCLUSION: Leukotriene antagonists, such
      as montelukast, may be better non-steroidal anti-inflammatory drugs for
      preventing airway inflammation in mild childhood asthma.

PMID- 18045298
TI  - Epidural air associated with spontaneous pneumomediastinum in children: uncommon
      complication?
AB  - BACKGROUND: The purpose of the present study was to evaluate the incidence of
      epidural air associated with spontaneous pneumomediastinum in children. METHODS:
      The subjects consisted of 25 boys and 17 girls with an age range of 3-14 years
      (mean age: 8.5 years) who underwent chest computed tomography (CT) for evaluation
      of spontaneous pneumomediastinum. The CT scans and medical records were reviewed
      retrospectively. RESULTS: Of the 42 patients, four (9.5%) had intraspinal air on
      CT. The air was interpreted as epidural in every patient. The small number of
      patients with epidural air meant that there was no significant difference in age,
      gender, or clinical manifestations between groups with and without epidural air.
      Subcutaneous emphysema was identified in all four patients with epidural air
      versus 18 out of 38 patients (47%) without epidural air. The patients with
      epidural air did not have any neurologic symptoms. Irrespective of the presence
      or absence of epidural air, every patient had a favorable outcome without any
      serious complications. CONCLUSION: In patients with spontaneous
      pneumomediastinum, epidural air may be more common than was previously realized.
      It is suggested that an air leak may spread from the mediastinum into the
      epidural space via the cervical fascial planes and neural foramina.

PMID- 18045299
TI  - Addition of sufentanil to bupivacaine in caudal block effect on stress responses
      in children.
AB  - BACKGROUND: The aim of the present randomized study was to determine the effect
      of adding sufentanil to bupivacaine, compared with bupivacaine alone in caudal
      block, on the surgical stress response in children. METHODS: The children were
      premedicated with midazolam 0.5 mg/kg. All children received induction with
      nitrous oxide and sevoflurane. Anesthesia was maintained with the same volatile
      agents in the both groups. The children were randomly allocated to two groups.
      Group I received bupivacaine alone (n = 17) and group II received bupivacaine +
      sufentanil (n = 16). Caudal block was performed with 0.25% bupivacaine 2 mg/kg
      (group I) or 0.25% bupivacaine 2 mg/kg with sufentanil 0.5 microg/kg (group II)
      after induction of anesthesia. Blood samples were obtained after induction of
      anesthesia (T(0)) to measure baseline concentrations of cortisol, prolactin,
      glucose and insulin. Additional samples were obtained 30 min after the start of
      surgery (T(1)), and 60 min after the end of surgery (T(2)). RESULTS: All of the
      basal values (T(0)) were within the normal ranges of the authors' laboratory for
      children of this age group and there were no differences between the groups (P >
      0.05). In both groups, glucose concentration increased at T(1), compared with
      T(0) and T(2) (P < 0.05). The glucose concentration was unchanged at T(2)
      compared with T(0) in both group (P > 0.05). In both groups, prolactin
      concentration increased at T(1), compared with T(0) and decreased at T(2),
      compared with T(1) (P < 0.05). Cortisol decreased at T(1) and T(2), compared with
      T(0) in both groups. (P < 0.05). Insulin concentration remained unchanged at T(0)
      and T(2), but increased slightly at T(1) in both groups (P > 0.05). There were no
      significant differences in plasma prolactin, cortisol, glucose and insulin levels
      between the two groups at T(1) and T(2) (P > 0.05). CONCLUSION: There is no
      advantage in adding 0.5 microg/kg sufentanil to bupivacaine over bupivacaine
      alone in the caudal block, with regard to the surgical stress response in
      children.

PMID- 18045300
TI  - Mycophenolate mofetil therapy for children with intractable nephrotic syndrome.
AB  - BACKGROUND: Cyclosporin A (CyA) can suppress relapses and reduce proteinuria in
      frequent-relapse nephrotic syndrome (FRNS) and steroid-resistant nephrotic
      syndrome (SRNS). However, some patients remain resistant to CyA therapy. The
      purpose of the present paper was to evaluate mycophenolate mofetil (MMF)
      treatment in pediatric patients with CyA-resistant intractable nephrotic
      syndrome. METHODS: MMF therapy was given to 11 patients with FRNS who had relapse
      despite CyA therapy, and one patient with SRNS who had been receiving combined
      therapy using steroid and CyA until immediately before the start of MMF. MMF was
      administered at a daily dose of 750-1000 mg/m(2) in two divided doses. RESULTS:
      Ten of the 11 patients with FRNS were able to maintain remission. Among them,
      seven patients remained relapse free for 1 year, and two patients had a decrease
      in the frequency of relapse after initiation of MMF therapy. One patient,
      however, had repeated cycles of remission and relapse, and was considered
      resistant to MMF therapy. The total prednisolone dose during the period from
      month 6 to month 12 after the start of MMF therapy was significantly lower than
      that during the 6 month period before the start of MMF therapy. The patient with
      SRNS, who had not achieved remission despite CyA administration, had complete
      remission on MMF. No serious adverse effects were seen in any of the present
      patients. CONCLUSION: MMF could be useful in CyA-treatment-refractory FRNS and
      CyA-resistant SRNS.

PMID- 18045301
TI  - Menstrual pattern and common menstrual disorders among university students in
      Turkey.
AB  - BACKGROUND: Menstrual disorders may affect the life of adolescents and young
      adult women, and may sometimes cause serious problems. The patterns of menstrual
      cycles were analyzed for association with age of menarche, prevalence of
      menstrual irregularity, dysmenorrhea, prolonged menstrual bleeding, and effect of
      menstrual disorders, especially dysmenorrhea, on social activities and school
      attendance among the female students. METHODS: A total of 480 students were
      randomly selected and asked to complete an the anonymous questionnaire of 25
      items. RESULTS: The mean age of the subjects at menarche was 12.8 +/- 1.3 years
      with a range of 9-17 years. The duration between two periods and the menstrual
      flow were 27.7 +/- 2.5 days and 5.8 +/- 1.4 days, respectively. The prevalence of
      menstrual irregularity, prolonged menstrual bleeding and dysmenorrhea were 31.2%,
      5.3% and 89.5%, respectively. Approximately 10% of dysmenorrheic subjects had
      severe dysmenorrhea; and school absenteeism and need to consult a physician were
      more common in those subjects. The first source of their knowledge about menarche
      and menstruation was their mothers in 211 subjects (54%); only 18 subjects (4.6%)
      were given a lecture about menstruation and menarche at school. CONCLUSION: The
      prevalence of dysmenorrhea and menstrual irregularity was high, and most
      adolescents have inappropriate and insufficient information about menstrual
      problems. Hence, an education program is needed at the end of primary school
      about menarche and menstrual problems.

PMID- 18045302
TI  - Prevalence and clinical findings of migraine and tension-type headache in
      adolescents.
AB  - BACKGROUND: The majority of previous studies on headache in children and
      adolescents have focused mainly on migraine. There is a paucity of population
      based studies investigating the prevalence of tension-type headache (TTH). The
      objectives of the present study were to estimate the prevalence of migraine and
      TTH in adolescents using the 2004 International Headache Society (IHS) criteria
      and to determine the sociodemographic and clinical differences between the
      migraine and TTH. METHODS: Stratified group sampling was used in the present
      analytic, school-based, cross-sectional study. From the city of Izmir, 2384
      students aged 14-18 years were invited to complete a questionnaire. RESULTS:
      Migraine was found to be more common than TTH (21.3% vs 5.1%). The prevalence
      increased considerably to 29.9 and 15%, respectively, when the criteria defining
      the number and duration of headaches were excluded. All types of headaches were
      more frequent in female subjects but no significant difference was found in
      gender between the headache groups (P= 0.073). Headache in temples, number of
      siblings (more than one sibling), mother's and father's education (at least high
      school graduation) were more commonly seen in students with TTH. Absenteeism rate
      due to the headache was found to be higher in the migraine group than in the TTH
      group (P= 0.000). CONCLUSIONS: Migraine and TTH were found to be common types of
      headaches in adolescents. It was thought that, with the use of modified IHS
      criteria, the number of undiagnosed patients with headache will decrease.

PMID- 18045303
TI  - Preliminary early intervention study using Nursing Child Assessment Teaching
      Scale in Japan.
AB  - BACKGROUND: Mother-infant interactions have been acknowledged as one of the most
      important elements in measuring outcomes of parent support and infant mental
      health interventions. The present study was conducted to measure early
      intervention outcomes using the Nursing Child Assessment Teaching Scale (NCATS),
      and to identify factors that affected Japanese mother-infant interactions.
      METHODS: Healthy Japanese mother-infant dyads who had lower scores on the NCATS,
      indicating potential problems, were assigned to an intervention group, and
      compared with a control group who had higher scores on NCATS. Health-care
      professionals visited the intervention group dyads in their homes, and gave them
      positive feedback on their interactions, consultations on parenting, and health
      advice. The control group dyads had home visitation once every 6 months for
      assessment only. RESULTS: The home visitations started at 3 months of age and
      continued until 18 months. NCATS scores in both groups were significantly
      different at baseline but differences faded by the end, which suggests that the
      intervention promoted improved interactions in the intervention group. Two of
      five factors were identified as influencing mother-infant interactions: maternal
      age; and personal networks, and together they significantly explained 27-30% of
      NCATS variance. CONCLUSION: The results appear to support the validity of
      measuring Japanese mother-infant interactions with NCATS. This study is the first
      to measure the outcomes of early intervention on Japanese dyads' interactions
      using NCATS. Additional replication studies should be conducted elsewhere in
      Japan, and clinical practices for promoting mother-infant interactions should
      begin to assess their effectiveness with NCATS as an outcome measure.

PMID- 18045304
TI  - Roles of specific cytokines in bone remodeling and hematopoiesis in Gaucher
      disease.
AB  - BACKGROUND: Gaucher disease type 1 and type 3 are characterized by bone disease
      and hematological symptoms. It is known that monocyte/macrophage lineage is
      activated in Gaucher disease, and accordingly certain cytokines are elevated in
      blood. The aim of the present study was to explore the possible relationships
      between cytokines and bone remodeling and hematological abnormalities in this
      disease. METHODS: The concentrations of seven cytokines and two related proteins
      were measured in patients with Gaucher disease type 1 and type 3 (n= 8; age
      range, 2-50 years) who had received enzyme replacement therapy. RESULTS:
      Concentrations of interleukin-18 and transforming growth factor-beta1 were
      elevated in patients of all clinical types. Elevation of these cytokines in
      Gaucher disease has not been previously reported. Analysis of correlation among
      cytokines and bone-turnover markers showed that interleukin-18 concentration was
      correlated with each of two bone formation markers of bone-specific alkaline
      phosphatase activity and osteocalcin concentration, whereas macrophage colony
      stimulating factor concentration correlated with the bone absorption marker of N
      telopeptide to helix in urine. Concentrations of macrophage colony-stimulating
      factor and tumor necrosis factor-alpha were inversely correlated with hemoglobin
      concentration. CONCLUSIONS: Interleukin-18 and monocyte macrophage colony
      stimulating factor are cytokines mainly involved in the mechanism of bone
      disease, while macrophage colony-stimulating factor and tumor necrosis factor
      alpha may play a role in the development of hematological abnormalities in
      Gaucher disease.

PMID- 18045305
TI  - Stromal cell-derived factor-1alpha improves infarcted heart function through
      angiogenesis in mice.
AB  - BACKGROUND: Local delivery of stromal cell-derived factor-1alpha (SDF-1) has been
      demonstrated to improve hind limb ischemia through enhanced neovascularization in
      animals. It was hypothesized that local administration of SDF-1 also contributes
      to neovascularization of ischemic heart. METHOD: Acute myocardial infarction was
      created by left coronary artery ligation in C57BL/6J mice. Immediately after
      infarction induction, mice were treated by injection directly into the center of
      ischemic myocardium either with saline (control group) or SDF-1 (SDF-1 group).
      Cardiac function was measured on echocardiogram 2 and 4 weeks after infarction.
      On week 4 mice were killed to evaluate infarction size and capillary vessel
      density. To determine the contribution of bone marrow cells to angiogenesis, the
      same procedures were performed on C57BL/6J chimeric mice reconstituted with green
      fluorescent protein-positive bone marrow cells. RESULTS: Fractional shortening
      was greater in the SDF-1 group at 4 weeks (0.31 +/- 0.06% vs 0.23 +/- 0.03%, P =
      0.037). The infarct area was smaller in the SDF-1 group compared to the control
      group (9.31 +/- 2.76% vs 18.07 +/- 5.69%, P = 0.028). Green fluorescent protein
      positive cells accumulated predominantly at the peri-infarction site, and were
      located with the capillary vessels. Capillary vessel density was significantly
      increased in the SDF-1 group (13.08 +/- 4.11 vessels/mm(2) vs 34.50 +/- 7.59
      vessels/mm(2), P = 0.014). CONCLUSIONS: SDF-1 protects against deterioration of
      cardiac function after acute myocardial infarction by promoting angiogenesis. The
      safety and long-term prognosis of this treatment remains to be determined.

PMID- 18045307
TI  - Study of Japanese encephalitis and other viral encephalitis in Nepali children.
AB  - BACKGROUND: A hospital-based prospective cross-sectional study was conducted in
      children aged 1 month-14 years to identify the proportion of viral encephalitis
      due to Japanese encephalitis (JE) and compare the clinico-laboratory profile and
      outcome of JE with that of other viral encephalitis (non-JE). METHODS: All
      probable cases of viral encephalitis on clinical and laboratory evaluation were
      confirmed as JE on anti-JE IgM in cerebrospinal fluid (CSF) and/or serum.
      Patients not having anti-JE IgM in CSF and/or serum were diagnosed as having non
      JE. RESULTS: Of 94 cases, 58 were JE and 36 non-JE. Although practice of rearing
      pigs at home was associated with JE (P = 0.0001), significantly higher serum
      creatinine, protein, aspartate aminotransferase and CSF protein levels were
      observed in non-JE. Longer duration of fever was associated with complete
      recovery in JE whereas shorter duration of fever was associated with recovery in
      non-JE. Risk of neurological sequelae (P = 0.01), especially hemiparesis (P =
      0.03) was significantly more in JE. Sequelae were observed at 6 weeks follow up
      in 18.8% of JE and 13.9% of non-JE. CONCLUSION: JE was the most common cause of
      viral encephalitis in eastern Nepal and should be suspected in encephalitic
      patients having pig rearing at home and neurological sequelae. Although duration
      of hospitalization and complication were higher in JE, final outcome was similar
      to non-JE. Longer duration of fever in JE and shorter duration of fever in non-JE
      correlated with recovery, while altered sensorium and focal neurological deficit
      were independent predictors of sequelae at 6 weeks only in JE and not in non-JE.

PMID- 18045306
TI  - Randomized controlled trial of short-term withdrawal of i.v. immunoglobulin
      therapy for selected children with human immunodeficiency virus infection.
AB  - BACKGROUND: The aim of the present paper was to determine whether monthly i.v.
      immunoglobulin (IVIG) could be safely discontinued in antiretroviral-treated
      human immunodeficiency virus (HIV)-infected children. METHODS: In a double-blind
      cross-over trial, children < or =18 years with HIV infection, well controlled on
      antiretroviral therapy, were randomized to alternating courses of 3 consecutive
      months of IVIG (400 mg/kg once a month) and 3 consecutive months of placebo for 1
      year. The primary outcome was days of fever per month. Secondary outcomes were
      frequency of serious infections, changes in HIV viral load (VL), CD4+ counts and
      IgG levels. RESULTS: Fifteen children were enrolled. Using the revised pediatric
      HIV clinical classification system of the Centers for Disease Control and
      Prevention, eight were severely symptomatic (C), four were moderately symptomatic
      (B) and three were mildly symptomatic (A). There were no statistically
      significant outcome measures. The mean number of days of fever per month with
      IVIG versus placebo was 0.55 days versus 1.48 days (P = 0.11). The difference was
      0.9 days (95% confidence interval: +2.05 to -0.25). There were no serious
      infections in either period. For the IVIG versus placebo periods, mean CD4 counts
      were 970 cells/microL versus 906 cells/microL (P = 0.12), VL 2.90 log(10)
      copies/mL versus 2.82 log(10) copies/mL (P = 0.70) and IgG levels were 17.41 g/L
      versus 16.6 g/L (P = 0.13). CONCLUSION: In antiretroviral-treated HIV-infected
      children short-term withdrawal of monthly IVIG was not associated with a
      significant increase in incidence of infections or a decline in immunologic
      function (CD4 count, viral load and IgG levels). These results suggest that
      monthly IVIG can be safely discontinued in HIV-infected children who are
      clinically stable and receiving combination antiretroviral therapy.

PMID- 18045308
TI  - Risk factors for small for gestational age.
AB  - BACKGROUND: The purpose of the paper was to determine the risk factors for small
      for-gestational-age (SGA) infants at full term, in Japan. METHODS: The study was
      conducted at four hospitals and clinics in the Tokyo metropolitan area. A
      retrospective review of 2972 mothers and their infants born from singleton
      pregnancies at any time during the years 2002 and 2003 was conducted. RESULTS: Of
      these women, 8.4% gave birth to SGA infants. The proportion of SGA infants was
      significantly higher among heavy smokers (>10 cigarettes/day; 13.7%, P < 0.01).
      The odds ratio (OR) for SGA decreased significantly in proportion to the
      pregnancy body mass index (OR, 0.89; 95% confidence interval [CI]: 0.84-0.94, P <
      0.001). The OR of SGA for stratified maternal weight gain was 1.79 (95%CI: 1.24
      2.58, P </= 0.01) for weight gain < 8.0 kg; 1.16 (95%CI: 0.79-1.71, P = 0.45) for
      weight gain 8.0-10.0 kg; and 0.49 (95%CI: 0.3-0.78, P < 0.01) for weight gain >12
      kg. CONCLUSION: The present study clearly confirms the detrimental effect of a
      low prepregnancy body mass index, low maternal weight gain and maternal smoking
      during pregnancy on the incidence of SGA infants.

PMID- 18045309
TI  - Are foot posture and functional health different in children with growing pains?
AB  - BACKGROUND: The aim of the present paper was to investigate and compare findings
      of foot posture and functional health between groups of children aged 4-6 years
      with and without leg pain (described as "growing pains"). The null hypothesis:
      that there is no difference in measures of either foot posture or functional
      health between groups of children with and without leg pain. METHODS: A
      stratified random sample of children was obtained. The children were identified
      with and without leg pain using a validated questionnaire for parents. The
      examiner was blind to the children's pain status. The schools and child care
      centers were from each geographical quadrant of metropolitan Adelaide and a
      northern rural region of South Australia. One hundred and eighty children (94
      boys, 86 girls) entered and completed the study. Children whose parents returned
      a completed questionnaire and consent form were entered into the study. All
      participants were assessed by the one examiner. The foot posture measures used
      were those found to be most reliable in previous studies and for which the intra
      rater reliability of the examiner was ascertained. RESULTS: Initial analysis of
      foot posture measures between the leg pain and no leg pains groups indicated a
      statistically significant result for the measure of navicular height, but only on
      the left side (P = 0.033). Logistic regression modeling showed that navicular
      height (left foot only) was positively yet weakly related to growing pains (odds
      ratio, 1.072; 95% confidence interval: 0.991-1.160) and the effect was not
      significant (P = 0.08). Measures of functional health returned many statistically
      significant yet weakly correlated relationships. CONCLUSIONS: The null hypothesis
      of the present study was supported in terms of clinical significance. While the
      foot posture measure of navicular height on the left foot was statistically
      significant it was not predictive for growing pains nor clinically significant as
      a measure between groups. The present study does not support the anatomical
      theory for growing pains and does not find a meaningful relationship between foot
      posture or functional health measures and leg pain in young children.

PMID- 18045310
TI  - Hemophagocytic lymphohistiocytosis in a human immunodeficiency virus-positive
      homosexual high school student.
AB  - The spread of human immunodeficiency virus (HIV) infection has exploded over the
      past two decades and such infections in young people are no longer uncommon.
      However, the major infection route of pediatric patients remains vertical
      transmission, and sexual, especially homosexual transmission, is highly unusual.
      We herein describe the case of a 17-year-old boy who developed hemophagocytic
      lymphohistiocytosis (HLH). Although HLH was remitted soon with dexamethasone
      therapy, an HIV infection caused by homosexual transmission was detected.

PMID- 18045311
TI  - Severe, widespread vasculopathy in late-onset group B streptococcal meningitis.
AB  - Although improvements in antimicrobial therapy during the last few decades have
      decreased mortality in childhood bacterial meningitis, some patients are left
      with neurologic sequelae. Cerebrovascular complications are often associated with
      unfavorable clinical outcome of the disease. We report a 36-day-old infant with
      severe, widespread cerebrovascular complications due to group B streptococcal
      meningitis. Magnetic resonance imaging (MRI) and magnetic resonance angiography
      (MRA) contributed to a non-invasive demonstration of meningeal inflammatory
      changes and vascular lesions with the meningitis in this patient.

PMID- 18045312
TI  - Acute pancreatitis complicating typhoid fever in a 4-year-old girl.
AB  - Pancreatitis represents an extremely rare complication of typhoid fever. Herein
      we report the case of a 4-year-old Bangladeshi girl with acute pancreatitis
      caused by Salmonella typhi.

PMID- 18045313
TI  - Juvenile form of myasthenia gravis presenting as recurrent pulmonary infection
      with atelectasis.
AB  - Myasthenia gravis (MG), a chronic disease characterized by unusual fatigability
      of voluntary muscles, was first described by Willis. Three forms of MG are seen
      in childhood: juvenile MG, congenital MG and transient neonatal MG. Aside from
      age of onset, there is no difference in terms of pathology and pathogenesis
      between juvenile MG and adult-onset MG. Juvenile MG, like adult MG, appears to
      result from T-cell-initiated antibodies directed against end-plate Ach receptor
      protein. The onset of juvenile myasthenia can be insidious, although at times it
      is rapid, often a sequel to an acute febrile illness. Generally, muscles
      innervated by the cranial nerves are affected first, with bilateral ptosis being
      the most common presenting sign. Generalized weakness and dysphagia are less
      common presenting symptoms, while the clinical course is highly variable.

PMID- 18045314
TI  - Nephrotic syndrome in mesangial proliferative lupus nephritis.
AB  - Renal involvement is a major complication of systemic lupus erythematosus (SLE)
      and occurs in 30-70% of patients with SLE. Lupus nephritis is classified into six
      classes (I-VI) by the International Society of Nephrology and Renal Pathology
      Society (ISN/RPS). Although nephrotic syndrome is commonly associated with
      diffuse (ISN/RPS class IV) or membranous (ISN/RPS class V) lupus nephritis,
      several reports have described nephrotic syndrome in adult patients with minimal
      mesangial lupus nephritis (ISN/RPS class I) or mesangial proliferative lupus
      nephritis (ISN/RPS class II). However, nephrotic syndrome in mesangial
      proliferative lupus nephritis has rarely been reported in children. Although the
      pathogenesis of nephrotic syndrome with mesangial lupus nephritis is incompletely
      understood, three potential mechanisms have been postulated including lupus
      nephritis itself, non-steroidal anti inflammatory drug (NSAID)-induced minimal
      change nephrotic syndrome (MCNS) and coincidental occurrence of MCNS. We describe
      here a child with mesangial proliferative lupus nephritis who developed MCNS.

PMID- 18045315
TI  - Inspiratory stridor in a 12-month-old girl.
AB  - Congenital tracheal stenosis is a rare disorder, characterized by the presence of
      focal or diffuse complete tracheal cartilage rings, resulting in a fixed tracheal
      narrowing. The entity may be seen in isolation or in conjunction with other
      malformations that include an anomalous right upper lobe bronchus. We here report
      the case of a 12-month-old girl who had severe bi-segmental congenital tracheal
      stenosis with the interposition of a tracheal bronchus between the two stenotic
      segments.

PMID- 18045316
TI  - Massive periosteal reaction a presenting feature of acute megakaryocytic
      leukemia.
AB  - Acute megakaryoblastic leukemia (AML M7) is a biologically heterogeneous form of
      acute myeloid leukemia accounting for 14.6% of cases. In many instances in the
      past, AML M7 has been classified as undifferentiated leukemia, myelodysplasia,
      myelofibrosis or some other disease because of its complex clinical presentation
      or the difficulty of obtaining and interpreting bone marrow samples. However,
      with currently available morphological, cytochemical, cytogenetic and
      immunophenotypic methods, AML M7 can now be reliably diagnosed. Although the
      radiographic spectrum of bony changes in leukemia have been well characterized,
      skeletal X-ray abnormalities in the setting of AML M7 in pediatric patients have
      been described in few reports that were associated with bone marrow fibrosis.
      Here we report on a 14-month-old girl who presented with a massive periosteal
      reaction of the extremities and clavicles associated with myelofibrosis, a
      presenting feature of AML M7. The bone changes were very unusual in this case.

PMID- 18045317
TI  - Successful high-dose methotrexate chemotherapy in a patient with acute
      lymphocytic leukemia who developed acute renal failure during the initial
      treatment.
AB  - Methotrexate (MTX) is a key drug in the chemotherapy for childhood acute
      lymphocytic leukemia (ALL). It is essential in the treatment of such areas as the
      central nervous system (CNS) and reproductive organs. High-dose chemotherapy is
      applied for this purpose to obtain an effective plasma concentration in the
      target organs. There are three major mechanisms of nephrotoxicity related with
      MTX. One is that induced by allergic reaction, which usually appears as
      interstitial nephritis. In this case MTX is contraindicated. Another is direct
      pharmacological toxicity against renal tubules. The third is precipitation of
      MTX, which plugs the renal tubules. The latter two are consequently dose
      dependent, and are usually associated with high-dose chemotherapy. To prevent
      these nephrotoxicities, hydration and alkalinization of the urine are performed
      to accelerate the urinary excretion and avoid the precipitation of MTX.

PMID- 18045318
TI  - Langerhans cell histiocytosis manifesting as recurrent simultaneous bilateral
      spontaneous pneumothorax in early infancy.
AB  - Langerhans cell histiocytosis (LCH) is a rare disorder characterized by
      infiltration of either single or multiple organs by a distinct cell type that is
      S-100 and CD1a positive and contains ultrastructural Birbeck granules on electron
      microscopy. Historically, LCH included four main clinical forms: Letter-Siwe
      disease, Hand-Schuller-Christian disease, eosinophilic granuloma (together
      grouped as histiocytosis) and Hashimoto-Pritzker disease. The writing group of
      the Histiocytotic Society in 1987 proposed the uniform term of 'Langerhans cell
      histiocytosis' to encompass all the aforementioned eponymous forms. Lung
      involvement occurs in up to half of all children with multisystem disease and
      usually parallels overall disease activity. Spontaneous pneumothorax (SP) occurs
      in approximately 10% of children with pulmonary disease and may be a fatal
      complication. Patients with pulmonary LCH are likely predisposed to the
      development of pneumothorax based on destructive changes in the lung parenchyma.
      Here, we report a case of multisystem LCH in which the patient presented at 2
      months of age because of simultaneous bilateral pneumothorax.

PMID- 18045319
TI  - New Japanese pediatric guidelines for the treatment and management of bronchial
      asthma.
AB  - There have been a number of guidelines for asthma treatment published throughout
      the world. However, childhood asthma guidelines must be developed in
      consideration of the background of the individual countries. The second version
      of the Japanese Pediatric Guideline for the Treatment and Management of Bronchial
      Asthma 2002 (JPGL 2002) was published by the Japanese Society of Pediatric
      Allergy and Clinical Immunology (JSPACI) in November 2002, and was popular among
      Japanese physicians. After the publication of the JPGL, the incidence of
      pediatric asthma deaths decreased in Japan. In JPGL 2005 the recommendations were
      re-edited based on Global Initiative for Asthma (GINA) and the JPGL 2002. In
      comparison to the GINA guidelines, the JPGL 2005 include a classification system
      of asthma severity, recommendations for long-term management organized by age, a
      special mention of infantile asthma, and an emphasis on prevention and early
      intervention.

PMID- 18045320
TI  - Software image alignment for X-ray microtomography with submicrometre resolution
      using a SEM-based X-ray microscope.
AB  - Improved X-ray sources and optics now enable X-ray imaging resolution down to
      approximately 50 nm for laboratory-based X-ray microscopy systems. This offers
      the potential for submicrometre resolution in tomography; however, achieving this
      resolution presents challenges due to system stability. We describe the use of
      software methods to enable submicrometre resolution of approximately 560 nm. This
      is a very high resolution for a modest laboratory-based point-projection X-ray
      tomography system. The hardware is based on a scanning electron microscope, and
      benefits from inline X-ray phase contrast to improve visibility of fine features.
      Improving the resolution achievable with the system enables it to be used to
      address a greater range of samples.

PMID- 18045321
TI  - A highly reliable and budget-friendly Peltier-cooled camera for biological
      fluorescence imaging microscopy.
AB  - The SAC8.5, a low-cost Peltier-cooled black and white 8-bit CCD camera for
      astronomy, was evaluated for its use in imaging microscopy. Two camera-microscope
      configurations were used: an epifluorescence microscope (Nikon Eclipse TE2000-U)
      and a bottom port laser scanning confocal microscope system (Zeiss LSCM 510
      META). Main advantages of the CCD camera over the currently used photomultiplier
      detection in the scanning setup are fast image capturing, stable background, an
      improved signal-to-noise ratio and good linearity. Based on DAPI-labelled Chinese
      Hamster Ovarian cells, the signal-to-noise ratio was estimated to be 4 times
      higher with respect to the currently used confocal photomultiplier detector. A
      linear relationship between the fluorescence signal and the FITC-inulin
      concentrations ranging from 0.05 to 1.8 mg mL(-1) could be established. With the
      SAC8.5 CCD camera and using DAPI, calcein-AM and propidium iodide we could also
      distinguish between viable, apoptotic and necrotic cells: exposure to CdCl(2)
      caused necrosis in A6 cells. Additional examples include the observation of wire
      like mitochondrial networks in Mito Tracker Green-loaded Madin-Darby canine
      kidney cells. Furthermore, it is straightforward to interface the SAC8.5 with
      automated shutters to prevent rapid fluorophore photobleaching via easy to use
      astrovideo software. In this study, we demonstrate that the SAC8.5 black and
      white CCD camera is an easy-to-implement and cost-conscious addition to
      quantitative fluorescence microfluorimetry on living tissues and is suitable for
      teaching laboratories.

PMID- 18045322
TI  - Statistical modelling of the geometry of planar sections of prostatic capillaries
      on the basis of stationary Strauss hard-core processes.
AB  - In a recent study, the capillarization of normal prostatic tissue and prostatic
      carcinoma tissue was characterized by means of explorative methods of spatial
      statistics. In the present paper, an attempt was made to go beyond the
      explorative approach and to characterize the observed point patterns of the
      capillary profiles on sections by means of a parametric model. For this purpose,
      the flexible class of Gibbs processes was considered. Specifically, stationary
      Strauss hard-core processes were fitted to the observed point patterns. The
      goodness of fit achieved by the model was checked by simulations with the Markov
      chain Monte Carlo method using the Metropolis-Hastings algorithm. Model fitting
      and simulations were performed with the help of the spatstat package under R. The
      observed point patterns were in some cases compatible with realizations of
      stationary Strauss hard-core processes for all ranges of spatial interaction.
      However, deviations from the model were found for one or more domains of ranges
      in other cases. In the tumour tissue, a highly significant decrease of the
      interaction parameter of the Strauss hard-core process could be found as compared
      to the normal prostatic tissue. This finding is discussed in terms of a loss of
      the normal lobular architecture of the glands in the tumour tissue.

PMID- 18045323
TI  - Analytic solutions to modelling exponential and harmonic functions using
      Chebyshev polynomials: fitting frequency-domain lifetime images with
      photobleaching.
AB  - A novel approach is introduced for modelling linear dynamic systems composed of
      exponentials and harmonics. The method improves the speed of current numerical
      techniques up to 1000-fold for problems that have solutions of multiple
      exponentials plus harmonics and decaying components. Such signals are common in
      fluorescence microscopy experiments. Selective constraints of the parameters
      being fitted are allowed. This method, using discrete Chebyshev transforms, will
      correctly fit large volumes of data using a noniterative, single-pass routine
      that is fast enough to analyse images in real time. The method is applied to
      fluorescence lifetime imaging data in the frequency domain with varying degrees
      of photobleaching over the time of total data acquisition. The accuracy of the
      Chebyshev method is compared to a simple rapid discrete Fourier transform
      (equivalent to least-squares fitting) that does not take the photobleaching into
      account. The method can be extended to other linear systems composed of different
      functions. Simulations are performed and applications are described showing the
      utility of the method, in particular in the area of fluorescence microscopy.

PMID- 18045324
TI  - The large-scale digital cell analysis system: an open system for nonperturbing
      live cell imaging.
AB  - The Large-Scale Digital Cell Analysis System (LSDCAS) was designed to provide a
      highly extensible open source live cell imaging system. Analysis of cell growth
      data has demonstrated a lack of perturbation in cells imaged using LSDCAS,
      through reference to cell growth data from cells growing in CO(2) incubators.
      LSDCAS consists of data acquisition, data management and data analysis software,
      and is currently a Core research facility at the Holden Comprehensive Cancer
      Center at the University of Iowa. Using LSDCAS analysis software, this report and
      others show that although phase-contrast imaging has no apparent effect on cell
      growth kinetics and viability, fluorescent image acquisition in the cell lines
      tested caused a measurable level of growth perturbation using LSDCAS. This report
      describes the current design of the system, reasons for the implemented design,
      and details its basic functionality. The LSDCAS software runs on the GNU/Linux
      operating system, and provides easy to use, graphical programs for data
      acquisition and quantitative analysis of cells imaged with phase-contrast or
      fluorescence microscopy (alone or in combination), and complete source code is
      freely available under the terms of the GNU Public Software License at the
      project website (http://lsdcas.engineering.uiowa.edu).

PMID- 18045325
TI  - In situ fluorescence microscopy of bacteriophage aggregates.
AB  - Virus aggregation is analyzed because of its potential use for both classifying
      viruses and understanding virus ecology and evolution. Virus aggregation is,
      however, problematic because aggregation causes loss of virions during processing
      for microscopy of any type. Thus, here we detect virus aggregation by
      fluorescence microscopy of wet-mounted dissections of dilute gel-supported
      plaques (in situ fluorescence microscopy) of a test virus, the long-tail
      aggregating Bacillus thuringiensis bacteriophage, 0305phi8-36. Background
      fluorescence is reduced to nonproblematic levels by using the dye, DAPI (4',6
      diamidino-2-phenylindole), to stain viral nucleic acid. In situ fluorescence
      microscopy reveals two in situ phases, one weakly fluorescent. Most
      bacteriophages partition to the weakly fluorescent phase. Aggregates of
      bacteriophage 0305phi8-36 are detected during fluorescence microscopy via the
      following. (1) Coordinated motion is found for visibly separate particles in
      solution; the motion is either thermally generated, fluid drift-induced or
      mechanical pressure-induced. (2) Aggregate dissociation is observed. Some of the
      larger aggregates are elastic and entangled with material of the weakly
      fluorescent phase. The larger aggregates sometimes sink at 1-g within specimens.
      In situ fluorescence microscopy rapidly distinguishes 0305phi8-36 from
      nonaggregating bacteriophages.

PMID- 18045326
TI  - Can scanning near-field optical microscopy be compared with confocal laser
      scanning microscopy? A preliminary study on alpha-sarcoglycan and beta1D-integrin
      in human skeletal muscle.
AB  - The dystrophin-glycoprotein complex and the vinculin-talin-integrin system
      constitute, together a protein machinery, called costameres. The dystrophin
      glycoprotein complex contains, among other proteins, also dystrophin and the
      sarcoglycans subcomplex, proteins playing a key role in the pathogenesis of many
      muscular dystrophies and linking the cytoplasmic myofibrillar contractile
      elements to the signal transducing molecules of the extracellular matrix, also
      providing structural support to the sarcolemma. The vinculin-talin-integrin
      system connects some components of the extracellular matrix with intermediate
      filaments of desmin, forming transverse bridges between Z and M lines. In our
      previous reports we always studied these systems by confocal laser scanning
      microscopy (CLSM). In this paper we report on the first applications of optical
      near-field fluorescence microscopy to the spatial localization of alpha
      sarcoglycan and beta1D-integrin in human skeletal muscle fibres in order to
      better compare and test the images obtained with conventional CLSM and with
      scanning near-field optical microscopy (SNOM). In addition, the analysis of the
      surface morphology, and the comparison with the fluorescence map is put forward
      and analyzed for the first time on human muscle fibres. In aperture-SNOM the
      sample is excited through the nanometre-scale aperture produced at the apex of an
      optical fibre after tapering and subsequent metal coating. The acquisition of the
      topography map, simultaneously to the optical signal, by SNOM, permits to exactly
      overlap the fluorescence images obtained from the two consecutive scans needed
      for the double localization. Besides, the differences between the topography and
      the optical spatial patterns permit to assess the absence of artefacts in the
      fluorescence maps. Although the SNOM represented a good method of analysis, this
      technique remains a complementary method to the CLSM and it can be accepted in
      order to confirm the hypothesis advanced by CLSM.

PMID- 18045327
TI  - Optimization of multiphoton excitation microscopy by total emission detection
      using a parabolic light reflector.
AB  - We have constructed a device that maximizes the probability of collecting all of
      the scattered and ballistic light isotropically generated at the focal spot of
      multiphoton excited emissions (MPE) to optimize the signal-to-noise ratio (SNR)
      for micro-imaging. This was accomplished by optically coupling a parabolic
      reflector (that surrounds the sample and top of the objective) to a pair of
      collimating lenses (above the sample) that redirects emitted light to a separate
      detector. These additional optics, combined with the objective, allow the total
      emission detection (TED) condition to be approached. Numerical simulations
      suggest an approximately 10-fold improvement in SNR with TED. Comparisons between
      the objective detection and TED reveal an enhancement of 8.9 in SNR (77% of
      predicted) for GFP-labelled brain slices and similar results for fluorescent
      beads. This increase in SNR can be used to improve time resolution, reduce laser
      power requirements/photodynamic damage, and, in certain cases, detection depth,
      for MPE imaging techniques.

PMID- 18045328
TI  - Analytical TEM study of annealed nanocrystalline cobalt-phosphorous
      electrodeposits.
AB  - Investigation of thermal stability of two nanocrystalline Co-P alloys shows that
      P atoms segregate to the grain boundaries upon annealing until precipitation of
      Co(2)P and CoP precipitates takes place. The P-rich precipitates formed have been
      investigated by analytical transmission electron microscopy to obtain statistical
      results of precipitate size, volume fraction and spatial distribution. Electron
      spectroscopic imaging maps show that the P-rich precipitates are 33 +/- 9 nm in
      Co-1.1at.%P and 33 +/- 12 nm in Co-3.2at.%P. The main differences between the
      alloys are the precipitate size distribution (Co-3.2at.%P having broader
      distribution) and precipitate volume number density (Co-3.2at.%P has 1.8 times
      more precipitates than Co-1.1at.%P). The volume fraction of precipitates is 3.0%
      in Co-1.1at.%P and 4.4% in Co-1.1at.%P. Most of the precipitates are of nearly
      spherical or slightly elongated shape, and only a few have a platelet-like shape
      as expected from previous tomographic atom probe measurements. Due to the
      truncation and projection effects, the composition of the precipitates could not
      be determined.

PMID- 18045329
TI  - The morphology of the inner ear from the domestic pig (Sus scrofa).
AB  - The morphology of the hair cells of the inner ear end organs from the domestic
      pig (Sus scrofa) have been studied using a combination of Scanning and
      Transmission Electron Microscopy (SEM and TEM), revealing hair cells from the
      cochlea and vestibule using a novel surgical and technical approach. This is the
      first time that the inner ear hair cells from S. scrofa have been studied, thus
      providing useful anatomical information on the morphology of the hair cells from
      the cochlea, saccule and utricle from a large mammal. Anatomical information in
      relation to the morphology of the inner ear is of considerable importance, both
      in the pathological diagnosis of trauma and in the development of cochlea
      implants and other biotechnological systems associated with the enhancement of
      hearing. Standard fixation protocols using cardiac perfusion was not employed in
      this study as this method cannot always be applied, such as the pathological
      examination of the human ear, or the study of animals protected by endangered
      species legislation. With the exception of a very few countries, cetaceans cannot
      be killed for research purposes, yet physiological information on the inner ear
      from these species is urgently required for ecological assessment reasons.
      Supporting the use of S. scrofa as a model for cetacean hearing research is that
      this animal is a member of the order Artiodactyla, which includes both the
      hippopotamus and cetaceans. Being of a similar size, the pig is an ideal subject
      for developing protocols and surgical techniques required to investigate both the
      human and small cetacean auditory systems.

PMID- 18045330
TI  - Morphological analyses of minute crystals by using stereo-photogrammetric
      scanning electron microscopy and electron back-scattered diffraction.
AB  - We present a new method for the morphological analyses of minute faceted crystals
      by combining stereo-photogrammetric analysis of scanning electron microscope
      images and electron back-scattered diffraction. Two scanning electron microscope
      images of the same crystal, recorded at different tilt angles of the specimen
      stage, are used to determine the orientations of crystal edges in a specimen
      fixed coordinate system. The edge orientations are converted to the indices [uvw]
      in the crystal system using the crystal orientation determined by electron back
      scattered diffraction analysis. The Miller indices of crystal facets are derived
      from the indices of the edges surrounding the facets. The method is applicable to
      very small crystal facets. The angular error, as derived from tests using a
      calcite crystal of known morphology, is a few degrees. To demonstrate the
      applicability of the method, the morphology of boehmite (gamma-AlOOH)
      precipitated from solution during the dissolution of anorthite was analyzed. The
      micrometre-sized boehmite crystals are surrounded by two {010} basal facets and
      eight equivalent side facets that can be indexed equally well as {323}, {434} or
      {545}. We suggest that these side facets are in fact {111}, the morphology having
      been modified slightly (by a few degrees) by a small extension associated with
      opening along (010) microcleavage planes. Tiny {140} facets are also commonly
      observed.

PMID- 18045331
TI  - Near-field photothermal microspectroscopy for adult stem-cell identification and
      characterization.
AB  - The identification of stem cells in adult tissue is a challenging problem in
      biomedicine. Currently, stem cells are identified by individual epitopes, which
      are generally tissue specific. The discovery of a stem-cell marker common to
      other adult tissue types could open avenues in the development of therapeutic
      stem-cell strategies. We report the use of the novel technique of Fourier
      transform infrared near-field photothermal microspectroscopy (FTIR-PTMS) for the
      characterization of stem cells, transit amplifying (TA) cells and terminally
      differentiated (TD) cells in the corneal epithelium. Principal component analysis
      (PCA) data demonstrate excellent discrimination of cell type by spectra. PCA in
      combination with linear discriminant analysis (PCA-LDA) shows that FTIR-PTMS very
      effectively discriminates between the three cell populations. Statistically
      significant differences above the 99% confidence level between IR spectra from
      stem cells and TA cells suggest that nucleic acid conformational changes are an
      important component of the differences between spectral data from the two cell
      types. FTIR-PTMS is a new addition to existing spectroscopy methods based on the
      concept of interfacing a conventional FTIR spectrometer with an atomic force
      microscope equipped with a near-field thermal sensing probe. FTIR-PTMS
      spectroscopy currently has spatial resolution that is similar to that of
      diffraction-limited optical detection FTIR spectroscopy techniques, but as a near
      field probing technique has considerable potential for further improvement. Our
      work also suggests that FTIR-PTMS is potentially more sensitive than synchrotron
      radiation FTIR spectroscopy for some applications. Microspectroscopy techniques
      like FTIR-PTMS provide information about the entire molecular composition of
      cells, in contrast to epitope recognition that only considers the presence or
      absence of individual molecules. Our results with FTIR-PTMS on corneal stem cells
      are promising for the potential development of an IR spectral fingerprint for
      stem cells.

PMID- 18045332
TI  - Evaluation of intragranular misorientation parameters measured by EBSD in a hot
      worked austenitic stainless steel.
AB  - An extensive characterization of hot deformed austenitic stainless steel was
      carried out using the electron backscatter diffraction technique. Special
      emphasis was given to the misorientation parameters related to different length
      scales. These parameters show a behaviour that is sensitive to the amount of
      applied strain and also lead to increasing values for both the strain and the
      scale length. At the same time, the use of different thresholds and scan steps in
      the evaluation of the parameters were analyzed in order to assess the validity of
      the results.

PMID- 18045333
TI  - Modular software platform for low-dose electron microscopy and tomography.
AB  - Transmission electron microscopy imaging protocols required by structural
      scientists vary widely and can be laborious without tailor-made applications. We
      present here the jeol automated microscopy expert system (james) api integrator,
      a programming library for computer control of transmission electron microscopy
      operations and equipment. james has been implemented on JEOL microscopes with
      Gatan CCDs but is designed to be modular so it can be adapted to run on different
      microscopes and detectors. We have used the james api integrator to develop two
      applications for low-dose digital imaging: james imaging application and the mr t
      tomographic imaging application. Both applications have been widely used within
      our NCRR-supported Center for routine data collection and are now made available
      for public download.

PMID- 18045335
TI  - Automated electron tomography with scanning transmission electron microscopy.
AB  - We report the successful implementation of a fully automated tomographic data
      collection system in scanning transmission electron microscopy (STEM) mode.
      Autotracking is carried out by combining mechanical and electronic corrections
      for specimen movement. Autofocusing is based on contrast difference of a focus
      series of a small sample area. The focus gradient that exists in normal images
      due to specimen tilt is effectively removed by using dynamic focusing. An
      advantage of STEM tomography with dynamic focusing over TEM tomography is its
      ability to reconstruct large objects with a potentially higher resolution.

PMID- 18045334
TI  - Evaluating performance in three-dimensional fluorescence microscopy.
AB  - In biological fluorescence microscopy, image contrast is often degraded by a high
      background arising from out of focus regions of the specimen. This background can
      be greatly reduced or eliminated by several modes of thick specimen microscopy,
      including techniques such as 3-D deconvolution and confocal. There has been a
      great deal of interest and some confusion about which of these methods is
      'better', in principle or in practice. The motivation for the experiments
      reported here is to establish some rough guidelines for choosing the most
      appropriate method of microscopy for a given biological specimen. The approach is
      to compare the efficiency of photon collection, the image contrast and the signal
      to-noise ratio achieved by the different methods at equivalent illumination,
      using a specimen in which the amount of out of focus background is adjustable
      over the range encountered with biological samples. We compared spot scanning
      confocal, spinning disk confocal and wide-field/deconvolution (WFD) microscopes
      and find that the ratio of out of focus background to in-focus signal can be used
      to predict which method of microscopy will provide the most useful image. We also
      find that the precision of measurements of net fluorescence yield is very much
      lower than expected for all modes of microscopy. Our analysis enabled a clear,
      quantitative delineation of the appropriate use of different imaging modes
      relative to the ratio of out-of-focus background to in-focus signal, and defines
      an upper limit to the useful range of the three most common modes of imaging.

PMID- 18045336
TI  - Circadian variation of the Ca2+ -PTH curve during hypercalcaemia in dogs.
AB  - To test the hypothesis that the parathyroid hormone (PTH) response to
      hypercalcaemia is influenced by circadian rhythms, the Ca2+ -PTH curve was
      studied in six dogs after infusion of CaCl2 (0.66 mEq/kg/h) at daytime (09:00 h)
      and at night-time (21:00 h). Plasma Ca2+ and PTH values measured before or after
      CaCl2 infusion were not different at day and at night. However, in the recovery
      from hypercalcaemia, PTH concentrations were significantly lower (P < 0.05) at
      21:00 h (23 +/- 7.5 pg/ml at Ca2+ = 1.30 mm) than at 09:00 h (38.8 +/- 6.9 pg/ml
      at Ca2+ = 1.30 mm). In addition, the Ca2+ -PTH curve showed hysteresis at daytime
      (for the same Ca2+ concentration, PTH values were higher during recovery than
      during induction of hypercalcaemia) but not at night-time (PTH values were lower
      during recovery than during induction of hypercalcaemia). In conclusion, a
      circadian variation in the PTH secretory pattern during recovery from
      hypercalcaemia has been identified in dogs.

PMID- 18045337
TI  - Development-related expression of KGF and FGF-10 mRNA in the canine prostate
      gland.
AB  - Keratinocyte growth factor (KGF) and fibroblast growth factor 10 (FGF-10) are
      stromal-derived growth factors that interact with their epithelial FGFR2
      receptors to mediate stromal--epithelial cell interaction within the prostate
      gland. This study was conducted to compare the development-related mRNA
      expression of KGF, FGF-10 and their receptor FGFR2 in immature and mature canine
      prostate glands. In addition, their expression levels were correlated with the
      differentiation of stromal cells using vimentin as a mesenchymal cell marker.
      Quantitative mRNA expression was assessed by real-time polymerase chain reaction
      (PCR) and the results were expressed as relative mRNA expression of the target
      gene, which was normalized to the GAPDH reference gene. mRNA analysis revealed a
      differential expression of KGF, FGF-10 and FGFR2 receptor by the prostate glands
      of immature and mature dogs. The results showed a 7.3- and 9-fold decrease in
      mRNA expression of KGF and FGF-10 by mature and immature prostate glands
      respectively. However, there was no significant change in FGFR2 receptor mRNA
      expression by mature or immature prostate glands. This downregulation of KGF and
      FGF-10 expression was associated with a 15-fold decrease in vimentin expression.
      These results indicate that KGF and FGF-10 expression varied according to the
      differentiation status of stromal cells and might reflect differential
      developmental requirements of immature and mature canine prostate glands.

PMID- 18045338
TI  - Detection and localization of naturally transmitted avian leukosis subgroup J
      virus in egg-type chickens by in situ PCR hybridization.
AB  - Avian leukosis virus (ALV) subgroup J (ALV-J) is an exogenous ALV and causes
      myeloid leukosis in meat-type chickens. We have previously reported the isolation
      and identification of ALV-J in commercial layer flocks from 12 farms in northern
      China. In this report, we further characterized this virus by in situ polymerase
      chain reaction (PCR) hybridization in various affected organs of chickens from
      six of the 12 farms. A routine method for hybridization of nucleic acid uses
      radioactive probe, such as a P32-labelled probe. We found that the non
      radioactive digoxigenin (DIG) probe is sensitive enough to detect the nucleic
      acid of virus in chicken tissues. We used a pair of published primers (H5/H7)
      specific to the gp85 envelope gene and 3' region of pol gene of prototype ALV-J
      strain HPRS-103. The total RNA extracted from tumour, bone marrow, oviduct, liver
      and spleen of the diseased chickens from six commercial flocks, and cDNA was
      successfully amplified. Using the primers and cDNA, we obtained an ALV-J-specific
      cDNA probe of 545 bp in length by PCR. In situ PCR with H5/H7 primers was carried
      out in the paraffin sections from tissues of the diseased chickens, followed by
      in situ hybridization using the DIG-labelled cDNA probe. Positive hybridization
      signals were detected in the cytoplasm of paraffin sections of tumours and other
      organ tissues. The intensity of the signals was documented using an image
      analysis system measuring integral optical density (IOD). The IOD values for
      tissue sections treated by in situ PCR hybridization are significantly higher
      than that by in situ hybridization alone (P < 0.01). These data taken together
      suggest that in situ PCR hybridization is a more sensitive technique for
      detection of ALV-J in tissue sections.

PMID- 18045339
TI  - Identification and antimicrobial susceptibility of bacteria and yeasts isolated
      from healthy dogs and dogs with otitis externa.
AB  - The bacterial and fungal flora of the external ear canal of dogs with otitis
      externa and of healthy dogs were studied. The most frequently isolated
      microorganism from otitic ears was Staphylococcus intermedius (58.8%), followed
      by Malassezia pachydermatis (30.9%), Streptococcus canis (29.9%), Proteus spp.
      (14.4%) and Escherichia coli (10.3%). A statistical analysis of our results
      showed that the prevalence of these microorganisms is significant in dogs with
      otitis externa. Furthermore, the antimicrobial susceptibility patterns of
      isolated strains were determined. Majority of all bacterial isolates were most
      susceptible to gentamicin. Malassezia pachydermatis, the most prevalent yeast in
      this study, showed an excellent level of susceptibility to all antifungal agents
      tested.

PMID- 18045340
TI  - Proliferation of pulmonary artery smooth muscle cells in the development of
      ascites syndrome in broilers induced by low ambient temperature.
AB  - Pulmonary vascular remodelling, mainly characterized by arterial medial
      thickening, is an important pathological feature of broiler ascites syndrome
      (AS). Since vascular smooth muscle cells (VSMC) form the major cellular component
      of arterial medial layer, we speculate that VSMC proliferation is one of the
      causes of pulmonary arterial medial thickening in ascitic broilers. Hence, the
      present study was designed to investigate the role of VSMC proliferation in
      pulmonary vascular remodelling in development of AS induced by low ambient
      temperature. Broilers in control group (22 +/- 1.5 degrees C) and low temperature
      group (11 +/- 2 degrees C) were sampled every week at 15-50 days of age.
      Proliferative indexes of VSMC in pulmonary arteries were assessed with
      proliferating cell nuclear antigen, and the relative medial thickness (RMT) and
      relative wall area (RWA), as indexes of pulmonary vascular remodelling, were
      examined by computer-image analysing system. The results showed that the high
      incidence (18.75%) of AS was induced by low temperature, and a significantly
      increased VSMC proliferation was observed in pulmonary arteries in the low
      temperature group at 22-50 days of age (P < 0.05). In addition, RMT and RWA in
      pulmonary arteries were significantly elevated in the low temperature group from
      36 days of age (P < 0.05), indicating that pulmonary vascular remodelling
      occurred following VSMC proliferation in AS. Our data suggest that proliferation
      of VSMC may facilitate pulmonary vascular remodelling and have a pivotal role in
      AS induced by low ambient temperature.

PMID- 18045341
TI  - Immunohistochemical detection of porcine teschovirus antigen in the formalin
      fixed paraffin-embedded specimens from pigs experimentally infected with porcine
      teschovirus.
AB  - Porcine teschovirus (PTV) antigens were detected by a streptavidin-biotin complex
      method in formalin-fixed paraffin-embedded tissues of 3-week-old pigs that had
      been inoculated intravenously with PTV Talfan strain. PTV antigens were detected
      in cytoplasm of nerve cells, glial cells and endothelial cells in the cerebellar
      nuclei, the grey matter of the midbrain, pons and medulla oblongata and the
      ventral horn of the spinal cord and of ganglion cells in the spinal ganglion
      corresponding to those lesions characterized as non-suppurative encephalomyelitis
      and ganglionitis. The results of this study suggest that nerve cells of the brain
      stem and spinal cord and ganglion cells of the spinal ganglion permit PTV
      replication and represent the main target cell population of PTV. This is the
      first study to demonstrate PTV antigen by immunohistochemistry in formalin-fixed
      paraffin-embedded tissue specimens from pigs infected with PTV.

PMID- 18045342
TI  - A case of intravascular lymphoma with mixed lineage antigen expression in a cat.
AB  - A 3-year-old neutered male British shorthair cat was presented to the Clinic for
      Small Animal Medicine, Internal Medicine and Clinical Pathology, at the Justus
      Liebig-University Giessen with a short history of lethargy, severe dyspnoea,
      fever, anaemia, thrombocytopenia and hyperbilirubinaemia. In blood smears and
      lymph node aspirates, large pleomorphic lymphatic blasts were detected. On
      necropsy splenic infarcts and moderate hydrothorax as well as moderate ascites
      could be observed. Histological examination revealed large numbers of lymphoid
      blasts within the lumen of the vessels of the lung, lymph nodes, the liver, the
      chorioid coat of the eyes, in meningeal vessels, arteries and veins of the brain,
      and within the larger splenic vessels. Neoplastic cells immunohistochemically
      stained positive for CD45R and CD3. Based on these findings, an intravascular
      lymphoma was diagnosed.

PMID- 18045343
TI  - Kinematic gait analysis of the hind limb after tibial plateau levelling osteotomy
      and cranial tibial wedge osteotomy in ten dogs.
AB  - This study identifies and compares the kinematic gait changes occurring in tibial
      plateau levelling osteotomy (TPLO) and cranial tibial wedge osteotomy (CTWO)
      limbs after transection of the cranial cruciate ligament (CrCL). Ten, healthy,
      adult beagle dogs were assigned to TPLO (five dogs) and CTWO (five dogs) groups.
      Hind limb kinematics were assessed, while dogs were trotted at speeds ranging
      from 2.0 to 2.3 m/s. The animals were evaluated preoperatively (prior to TPLO and
      CTWO surgery) and at both 8 and 12 weeks after surgery. Two-dimensional
      evaluation was synchronized to obtain the three-dimensional coordinates using the
      APAS motion analysis software. Gait patterns were assessed by measuring stifle,
      tibiotarsal joint angles and stifle joints angular velocity. Stifle and
      tibiotarsal joint functions were not affected by TPLO surgery, but stifle and
      tibiotarsal joint angles were changed, following CTWO surgery, compared with
      their preoperative values. The angular velocity patterns of CTWO were
      characterized by increased stifle joint extension velocity from the middle to end
      swing phase and decrease in the peak velocities (flexion) during swing phase.
      None of these changes was observed in the stance phase after the CTWO surgery.
      These kinematic results showed that dogs that underwent a CTWO procedure were
      more likely to have significantly hyperextended gait patterns of the swing phase
      postoperatively than the dogs that had a TPLO procedure for repair of a ruptured
      CrCL.

PMID- 18045344
TI  - Effects of 4-chloro-2,6-bis-(2-hydroxyl-benzyl)-phenol on healing of skin wounds
      and growth of bacteria.
AB  - In this investigation, the effects of synthesized 4-chloro-2,6-bis-(2-hydroxyl
      benzyl)-phenol (CBHBP) on cutaneous wound healing and growth of some of the wound
      contaminating microorganisms were studied. The antibacterial effects of this
      compound were then evaluated on Staphylococcus aureus (S. aureus), Pseudomonas
      aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Klebsiella spp., using
      solid dilution method. It was demonstrated that CBHBP has a significant
      antimicrobial activity against S. aureus but it is not effective in the case of
      other microorganisms studied in this experiment. The effect of local
      administration of CBHBP on healing of a standard full-thickness 2 cm skin
      incision of skeletally mature rats was evaluated. Histological changes together
      with mechanical properties and dry weight content of the healing tissues at the
      site of the lesions were assessed in treated and untreated animals. It was
      observed that the injured area of the treated animals was more organized and
      showed more fibroblasts and less inflammatory cells. Much better maturation
      criteria in treated tissues were observed in comparison with those of the
      untreated ones which contained numerous polymorphonuclear inflammatory cells
      after 14 days post-injury. Many infiltrated macrophages and lymphocytes were
      present even 28 days after injury induction in the haphazardly organized dermis
      and also in subcutaneous tissues of the untreated animals. The percentage dry
      weight content of the treated lesions at 14 days post-injury was remarkably
      higher than those of the untreated animals. The results of biomechanical tensile
      testing showed that the ultimate tensile strength and stress of the injured skin
      of the treated animals were higher than those of the untreated ones. From these
      results, it could be concluded that CBHBP can be effective on wound healing and
      may be considered as a treatment regimen after evaluating its mechanism of action
      as well as testing its contraindications.

PMID- 18045345
TI  - Effect of hydroxyethyl starch solution in normal horses and horses with colic or
      acute colitis.
AB  - Hydroxyethyl starch (HES) solution is an effective colloidal infusion solution in
      humans for treatment of hypovolaemic shock, but it has not been compared with
      fluids currently available for use in horses. On the basis of plasma-expanding
      effect of HES in normal horses, a 10% medium-molecular 200/0.5 solution of HES
      was subsequently tested in hypovolaemic horses. Six normal horses were given five
      protocols of a single infusion of HES at varying dosage rates (5, 10, 15 ml
      HES/kg), as well as isotonic saline (15 ml/kg) and hypertonic saline (4 ml/kg
      b.w.). Dehydrated horses suffering from acute colitis or those which had been
      treated surgically for ileus of the small or large intestine were given an i.v.
      infusion of 10 ml HES/kg in combination with 10 ml saline/kg. Clinical data and
      blood samples for testing were taken before the infusion, and then 10 min, 1 h,
      2, 4, 6, 8, 10, 12 and 24 h after infusion (a.i.). A significant decrease in
      haematocrit was observed in protocol 1-5 for a period of up to 4, 4, 10 h, 10 min
      and up to 10 min; in group of colitis, during the entire 24-h testing period, and
      in groups of ileus of small intestine and of large intestine, up to 4 and 10 h
      a.i. HES decreases better and longer-lasting haematocrit and total protein than
      either isotonic or hypertonic saline. Half-life of HES increases due to higher
      dosage (5.83, 7.63 and 11.48 h) and distribution is exclusively intravascular. In
      normal horses of protocol 1-3 using HES aPTT, sodium and potassium were within
      the physiological range. Serum amylase activity is increased in horses using HES.
      On the basis of this clinical study, the decreasing effect of urea and creatinine
      in colic patients after surgery and fewer instances of postoperative ileus a
      dosage of 10 ml HES/kg could be recommended.

PMID- 18045346
TI  - Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using
      magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a
      phase-I study.
AB  - Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a
      high relapse rate. In this study, a new treatment option based on immune
      stimulation by intra-tumoral delivery of three feline cytokine genes was
      performed. The objective of this phase-I dose-escalation study was to determine a
      safe dose for further evaluation in a subsequent phase-II trial. Twenty-five
      client-owned cats with clinical diagnosis of fibrosarcoma - primary tumours as
      well as recurrences - entered the study. Four increasing doses of plasmids coding
      for feIL-2, feIFN-gamma or feGM-CSF, respectively, were previously defined. In
      groups I, II, III and IV these doses were 15, 50, 150 and 450 microg per plasmid
      and a corresponding amount of magnetic nanoparticles. Two preoperative intra
      tumoral injections of the magnetic DNA solution were followed by magnetofection.
      A group of four control cats received only surgical treatment. Side effects were
      registered and graded according to the VCOG-CTCAE scale and correlated to
      treatment. Statistical analyses included one-way anova, post hoc and Kruskal
      Wallis tests. ELISA tests detecting plasma feIFN-gamma and plasma feGM-CSF were
      performed. One cat out of group IV (450 microg per plasmid) showed adverse events
      probably related to gene delivery. As these side effects were self-limiting and
      occurred only in one of eight cats in group IV, this dose was determined to be
      well tolerable. Altogether six cats developed local recurrences during a 1-year
      observation period. Four of these cats had been treated with dose IV. Regarding
      these observations, a subsequent phase-II trial including a representative amount
      of cats should be tested for the efficacy of dose IV as well as dose III.

PMID- 18045347
TI  - Pharmacokinetics and mammary residual depletion of erythromycin in healthy
      lactating ewes.
AB  - The aim of this investigation was to examine the pharmacokinetics and mammary
      excretion of erythromycin administered to lactating ewes (n = 6) by the
      intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes at a
      dosage of 10 mg/kg. Blood and milk samples were collected at pre-determined
      times, and a microbiological assay method was used to measure erythromycin
      concentrations in serum and milk. The concentration-time data were analysed by
      compartmental and non-compartmental kinetic methods. The serum concentration-time
      data of erythromycin were fit to a two-compartment model after i.v.
      administration and a one-compartment model with first-order absorption after i.m.
      and s.c. administration. The elimination half-life (t(1/2beta)) was 4.502 +/-
      1.487 h after i.v. administration, 4.874 +/- 0.296 h after i.m. administration
      and 6.536 +/- 0.151 h after s.c. administration. The clearance value (Cl tot)
      after i.v. dosing was 1.292 +/- 0.121 l/h/kg. After i.m. and s.c. administration,
      observed peak erthyromycin concentrations (Cmax) of 0.918 +/- 0.092 microg/ml and
      0.787 +/- 0.010 microg/ml were achieved at 0.75 and 1.0 h (Tmax) respectively.
      The bioavailability obtained after i.m. and s.c. administration was 91.178 +/-
      10.232% and 104.573 +/- 9.028% respectively. Erythromycin penetration from blood
      to milk was quick for all the routes of administration, and the high AUC milk/AUC
      serum (1.186, 1.057 and 1.108) and Cmax-milk/Cmax-serum ratios reached following
      i.v., i.m. and s.c. administration, respectively, indicated an extensive
      penetration of erythromycin into the milk.

PMID- 18045348
TI  - Insulin-like growth factor I concentration in dogs with inflammatory and
      neoplastic liver diseases.
AB  - Liver diseases are known to influence the serum concentration of insulin-like
      growth factor I (IGF-I) in humans, but such an effect has rarely been
      investigated in dogs. The aim of this study was to investigate serum IGF-I
      concentrations in dogs with primary liver diseases, in comparison with levels in
      healthy dogs and dogs with non-hepatic diseases. For this purpose, IGF-I serum
      concentrations were measured (DSL-5600 kit) in 36 dogs with various liver
      diseases and compared with 22 healthy controls and 20 dogs with non-hepatic
      diseases. The results showed that dogs with liver diseases had significantly
      lower IGF-I serum concentrations (P < 0.001) than clinical healthy dogs or dogs
      with non-hepatic diseases. But the results also indicate that the aetiology of
      liver disease has no influence on IGF-I serum concentration.

PMID- 18045349
TI  - Third degree atrioventricular block and accelerated idioventricular rhythm
      associated with a heart base chemodectoma in a syncopal Rottweiler.
AB  - A 7-year-old male intact Rottweiler was presented with a 1-week history of
      lethargy, anorexia, vomiting and multiple syncopal events. The results of the
      clinical examination and electrocardiography were consistent with a third degree
      atrioventricular block and an intermittent accelerated idioventricular rhythm.
      Haematology, serum biochemistry, serology for Borrelia burgdorferi, blood
      culture, total T4, thoracic radiography and echocardiography did not reveal the
      cause of the arrhythmia. Response to medical treatment with isoproterenol was
      poor. Pacemaker placement was declined by the owners and the dog was euthanized
      at their request. Histopathological examination of the heart revealed a
      chemodectoma at the base of the heart. There was no neoplastic infiltration of
      the conduction tissue. Potential mechanisms explaining the association of the
      arrhythmias and the tumour, such as vagal stimulation and neuroendocrine factors
      are discussed.

PMID- 18045350
TI  - Prolonged gestation in two Holstein cows: transabdominal ultrasonographic
      findings in late pregnancy and pathologic findings in the fetuses.
AB  - Prolonged pregnancy in cattle is a rare condition that is commonly accompanied
      with fetal adenohypophyseal hypoplasia. The final diagnosis is often challenging
      as breeding date error remains possible in virtually all situations. In this
      report, fetal wellbeing assessment is depicted in two Holstein cows suffered from
      prolonged pregnancy. Transabdominal ultrasonographic findings were compatible
      with healthy non-stressed fetuses. The clinical and pathologic findings
      encountered in both fetuses expelled after corticosteroid induction of
      parturition consisted of adenohypophyseal aplasia and hydronephrosis. Other
      nervous system anomalies (hydrocephaly or holocephaly) were observed. Tetralogy
      of Fallot was also found in one calf.

PMID- 18045351
TI  - Skeletal morphology and development of the olfactory region of Spea (Anura:
      Scaphiopodidae).
AB  - The nasal capsules of anurans are formed by an intricate set of sac-like cavities
      that house the olfactory organ and constitute the beginning of the respiratory
      system. In tadpoles, nasal capsules do not have a respiratory function, but each
      is composed of a single soft tissue cavity lined with olfactory epithelium. Our
      study has revealed that in Spea the nasal cartilages and septomaxillae are de
      novo adult structures that form dorsal to the larval skeleton of the ethmoid
      region. The only element of the adult nasal capsule that is partially derived
      from the larval skeleton is the solum nasi. Development of the nasal skeleton
      begins at about Gosner Stage 31, with chondrification of the septum nasi and
      lamina orbitonasalis. The alary cartilage and superior prenasal cartilage are the
      first of the anterior nasal cartilages to chondrify at Gosner Stage 37. By Gosner
      Stages 40/41, the ethmoid region is composed of the larval structures ventrally
      and the adult structures dorsally. By Stage 44, the larval structures have
      eroded. The adult nasal capsule is characterized by: (1) a septum nasi that
      projects ventrally beyond the plane of the nasal floor; (2) a paranasal
      commissure that forms the ventral margin of the fenestra nasolateralis; and (3) a
      large skeletal support for the eminentia olfactoria formed by the nasal floor and
      vomer. The timing of chondrification of the anterior nasal cartilages and the
      development of the postnasal wall, inferior prenasal cartilage, fenestra
      nasolateralis, and paranasal commissure are discussed and compared with those of
      other anuran species. This study also includes a discussion of the morphology of
      the skeletal support for the eminentia olfactoria, a structure best developed in
      distinctly ground-dwelling frogs such as spadefoot toads. Finally, we propose a
      more precise restriction of the terminology that is used to designate the
      posterior structures of the olfactory region of anurans.

PMID- 18045352
TI  - Micro-magnetic resonance imaging of avian embryos.
AB  - Chick embryos are useful models for probing developmental mechanisms including
      those involved in organogenesis. In addition to classic embryological
      manipulations, it is possible to test the function of molecules and genes while
      the embryo remains within the egg. Here we define conditions for imaging chick
      embryo anatomy and for visualising living quail embryos. We focus on the
      developing limb and describe how different tissues can be imaged using micro
      magnetic resonance imaging and this information then synthesised, using a three
      dimensional visualisation package, into detailed anatomy. We illustrate the
      potential for micro-magnetic resonance imaging to analyse phenotypic changes
      following chick limb manipulation. The work with the living quail embryos lays
      the foundations for using micro-magnetic resonance imaging as an experimental
      tool to follow the consequences of such manipulations over time.

PMID- 18045353
TI  - Estimation of dose requirements for sustained in vivo activity of a therapeutic
      human anti-CD20 antibody.
AB  - We evaluated the dose requirements for sustained in vivo activity of ofatumumab,
      a human anti-CD20 antibody under development for the treatment of B cell-mediated
      diseases. In a mouse xenograft model, a single dose, resulting in an initial
      plasma antibody concentration of 5 microg/ml, which was expected to result in
      full target saturation, effectively inhibited human B-cell tumour development.
      Tumour growth resumed when plasma concentrations dropped below levels that are
      expected to result in half-maximal saturation. Notably, tumour load significantly
      impacted antibody pharmacokinetics. In monkeys, initial depletion of circulating
      and tissue residing B cells required relatively high-dose levels. Re-population
      of B-cell compartments, however, only became detectable when ofatumumab levels
      dropped below 10 microg/ml. We conclude that, once saturation of CD20 throughout
      the body has been reached by high initial dosing, plasma concentrations that
      maintain target saturation on circulating cells (5-10 microg/ml) are probably
      sufficient for sustained biological activity. These observations may provide a
      rationale for establishing dosing schedules for maintenance immunotherapy
      following initial depletion of CD20 positive (tumour) cells.

PMID- 18045355
TI  - Skin lightening preparations and the hydroquinone controversy.
AB  - Skin lightening preparations are widely used in dermatology by persons of all
      Fitzpatrick skin types. Fitzpatrick skin types I-III require local pigment
      lightening for the treatment of hormonally induced melasma and postinflammatory
      hyperpigmentation caused by acne and trauma. Fitzpatrick skin types IV and darker
      have an even greater need for skin lightening for social reasons, as well as
      pigmentary changes that occur around the eyes, in the intertriginous areas,
      following dermatitis, or with acne and trauma. The gold standard dermatologic
      agent for skin lightening was hydroquinone, until regulatory agencies in Japan,
      Europe, and most recently in the United States questioned the safety of this
      substance. This has encouraged research into alternative agents to inhibit skin
      pigmentation such as retinoids, mequinol, azelaic acid, arbutin, kojic acid,
      aleosin, licorice extract, ascorbic acid, soy proteins, and N-acetyl glucosamine.
      The efficacy and safety of each of these ingredients is examined as possible
      topical alternatives to hydroquinone.

PMID- 18045356
TI  - Interaction of vitamins C and E as better cosmeceuticals.
AB  - Although many cosmeceutical formulations contain vitamin C and/or vitamin E, very
      few are actually effective in topical application. First because there is only a
      low concentration, second because the stability is compromised as soon as the
      product is opened and exposed to air and light, and third because the form of the
      molecule (an ester or a mixture of isomers) is not absorbed or metabolized
      effectively by the skin. However, when a stable formulation delivers a high
      concentration of the nonesterified, optimal isomer of the antioxidant, vitamins C
      and E do indeed inhibit the acute ultraviolet (UV) damage of erythema, sunburn,
      and tanning as well as chronic UV photoaging and skin cancer. Both are highly
      effective depigmenting agents. Topical vitamin C also increases collagen
      synthesis in both young and old fibroblasts. Because vitamin C regenerates
      oxidized vitamin E, the combination in a cosmeceutical formulation is synergistic
      - particularly in UV protection.

PMID- 18045357
TI  - Idebenone, green tea, and Coffeeberry extract: new and innovative antioxidants.
AB  - The use of topical antioxidants is gaining favor among dermatologists because of
      their broad biologic activity. Many are not only antioxidants but also have
      antiinflammatory and anticarcinogenic activities. Thus for dermatologists these
      cosmeceuticals have many potential applications. In general, topical antioxidants
      exert their effects by down-regulating free radical mediated pathways that damage
      skin. The present study will describe the science behind some of the newest
      topical antioxidants and outline how they can be used as part of a comprehensive
      skin care regimen.

PMID- 18045358
TI  - Less-known botanical cosmeceuticals.
AB  - Complementary and alternative medicine (CAM) has become increasingly popular in
      the United States during the last 10-15 years. The use of oral and topical
      supplements falls within this framework. Most oral and topical supplements are
      based on or include several botanical ingredients, many of which have long
      histories of traditional or folk medicine usage. Several of the available
      products derived from botanical sources are touted for their dermatologic
      benefits. The focus in this discussion will be on a select group of botanical
      compounds that have been used for dermatologic purposes or show promise for such
      applications, including: rosemary, polypodium leucotomos, propolis, oatmeal,
      olive oil, grape seed extract, lavender, mushrooms, and coffeeberry. Other more
      commonly used products of botanical origin, such as arnica, bromelain, caffeine,
      chamomile, ferulic acid, feverfew, green tea, licorice, pomegranate, and
      resveratrol, are also briefly considered.

PMID- 18045359
TI  - Cosmeceutical peptides.
AB  - Peptide cosmeceuticals are one of the new, popular options to treat aging skin.
      There are three main categories of cosmeceutical peptides: signal peptides,
      neurotransmitter-affecting peptides and carrier peptides. Although their benefits
      currently may not be as rigorously tested as most FDA-regulated drugs, the
      evidence to support their use is growing. This article attempts to review the
      various current popular cosmeceutical peptides, the published studies on their
      theoretical effects, and their practical use in dermatology.

PMID- 18045360
TI  - Endogenous growth factors as cosmeceuticals.
AB  - Growth factors play an important role in reversing the effects of skin aging
      mediated by chronological and environmental factors. Excessive oxidation of intra
      and extracellular components result in breakdown of collagen and elastin network
      in the dermis and produce the effect of facial aging. Topical application of
      human growth factors in multiple clinical studies has been shown to reduce the
      signs and symptoms of skin aging, including statically significant reduction in
      fine lines and wrinkles and increase in dermal collagen synthesis. More double
      blind and controlled studies are needed to confirm the preliminary clinical
      effects of growth factor products, and more controls on product quality and
      stability need to be established.

PMID- 18045362
TI  - Clinical expertise research: a history lesson from those who wrote it.

PMID- 18045361
TI  - Update on photoprotection.
AB  - Photoprotection is an effective method for preventing damaging effects from
      ultraviolet radiation (UVR). Photoprotection is accomplished through the use of
      sunscreens, protective clothing, and safe sun practices. Sunscreens are composed
      of various UV filters, including inorganic/physical blockers and organic/chemical
      sunscreen agents. New technologies are emerging in sunscreen development and may
      soon be available to U.S. consumers. General guidelines for sunscreen use should
      be reinforced to improve patient compliance and sunscreen efficacy. Habitual use
      of sunscreen is recommended with UV exposure, and concerns for vitamin D
      deficiency with sunscreen use should not supersede proper photoprotective
      behavior.

PMID- 18045363
TI  - Prototypes and semantic qualifiers: from past to present.

PMID- 18045364
TI  - Assessment: do we need to broaden our methodological horizons?

PMID- 18045365
TI  - An expert-performance perspective of research on medical expertise: the study of
      clinical performance.
AB  - CONTEXT: Three decades ago Elstein et al. published their classic book on medical
      expertise, in which they described their failure to identify superior performance
      by peer-nominated diagnosticians using high- and low-fidelity simulations of the
      everyday practice of doctors. OBJECTIVE: This paper reviews the results of
      subsequent research, with a particular emphasis on the progress toward Elstein et
      al.'s goal of capturing the essence of superior clinical performance in
      standardised settings in order to improve clinical practice. RESULTS: Research
      following publication of Elstein et al.'s book was influenced by laboratory
      research in cognitive psychology, which resulted in a redirection of its original
      focus on capturing clinical performance in practice to studies of changes in
      cognitive processes as functions of extended clinical experience. There is
      currently renewed interest in linking laboratory research with studies of the
      acquisition of superior (expert) performance in the clinic. CONCLUSIONS: Research
      on medical expertise and simulation training in technical procedures and
      diagnosis provide exciting opportunities for establishing translational research
      on the acquisition of superior (expert) performance in the clinic by capturing it
      with representative tasks in the laboratory, reproducing it for experimental
      analysis, and developing training activities, such as deliberate practice, that
      can induce measurable improvements in performance in the clinic.

PMID- 18045366
TI  - Found in translation: the impact of familiar symptom descriptions on diagnosis in
      novices.
AB  - CONTEXT: The language that patients use to communicate with doctors is quite
      different from the language of diagnosis. Patients may describe tiredness and
      swelling; doctors, fatigue and oedema. This paper addresses the process by which
      novices, who have learned standard medical terms for symptoms, use lay
      descriptions of symptoms to reach a diagnosis. Data in this paper indicate that
      the familiarity of the language used to describe symptoms influences diagnosis in
      novices and diagnosis does not, therefore, involve a simple translation into
      standard terms that are the basis of diagnostic decision. METHODS: A total of 24
      undergraduate students were trained to diagnose 4 pseudo-psychiatric disorders
      presented in written vignettes. Participants were tested on cases that contained
      2 equally probable diagnoses, in 1 of which the symptoms were expressed using
      previously seen descriptions. A deviation from 50:50 in reported diagnostic
      probabilities was expected if the familiar symptom descriptions biased diagnostic
      decisions. Twelve participants were tested immediately after training and 12
      after a 24-hour delay. RESULTS: Participants assigned greater diagnostic
      probability to the diagnosis supported by the familiar feature descriptions
      (F[1.242] = 19.35, P < 0.001, effect size = 0.40) on both immediate (52% versus
      41%) and delayed (51% versus 38%) testing. DISCUSSION: The findings indicate that
      diagnosis is not simply based on a process of translating patient descriptions of
      symptoms to standard medical labels for those symptoms, which are then used to
      make a diagnosis. Familiarity of symptom description has an effect on diagnosis
      and therefore has implications for medical education, and for electronic decision
      support systems.

PMID- 18045367
TI  - Teaching from the clinical reasoning literature: combined reasoning strategies
      help novice diagnosticians overcome misleading information.
AB  - OBJECTIVE: Previous research has revealed a pedagogical benefit of instructing
      novice diagnosticians to utilise a combined approach to clinical reasoning
      (familiarity-driven pattern recognition combined with a careful consideration of
      the presenting features) when diagnosing electrocardiograms (ECGs). This paper
      reports 2 studies demonstrating that the combined instructions are especially
      valuable in helping students overcome biasing influences. METHODS: Undergraduate
      psychology students were trained to diagnose 10 cardiac conditions via ECG
      presentation. Half of all participants were instructed to reason in a combined
      manner and half were given no explicit instruction regarding the diagnostic task.
      In Study 1 (n = 60), half of each group was biased towards an incorrect diagnosis
      through presentation of counter-indicative features. In Study 2 (n = 48), a third
      of the test ECGs were presented with a correct diagnostic suggestion, a third
      with an incorrect suggestion, and a third without a suggestion. RESULTS: Overall,
      the instruction to utilise a combined reasoning approach resulted in greater
      diagnostic accuracy relative to leaving students to their own intuitions
      regarding how best to approach new cases. The effect was particularly pronounced
      when cases were made challenging by biasing participants towards an incorrect
      diagnosis, either through mention of a specific feature or by making an
      inaccurate diagnostic suggestion. DISCUSSION: These studies advance a growing
      body of evidence suggesting that various diagnostic strategies identified in the
      literature on clinical reasoning are not mutually exclusive and that trainees can
      benefit from explicit guidance regarding the value of both analytic and non
      analytic reasoning tendencies.

PMID- 18045368
TI  - Clinical case processing: a diagnostic versus a management focus.
AB  - CONTEXT: Most studies on medical expertise research have focused on diagnostic
      performance, whereas patient management has been largely ignored. According to
      knowledge encapsulation theory, applying encapsulated knowledge is a
      characteristic of expert doctors' diagnostic reasoning, but it is unclear whether
      or not encapsulated knowledge also plays a prominent role when processing a
      clinical case with a management focus. METHODS: The participants were 40 medical
      students (20 in Year 4 and 20 in Year 6) and 20 expert doctors (internists).
      Participants were asked to study the cases with either a diagnostic (Dx) or a
      management (Mx) focus. Subsequently, participants were asked to write down what
      they remembered from the case. RESULTS: In both conditions, experts recalled
      fewer propositions and used more high-level inferences than medical students.
      Furthermore, they processed the cases faster and more accurately than medical
      students, but no significant difference between Mx and Dx conditions was found.
      Year 4 students also showed no significant differences in recall and processing
      speed between conditions. By contrast, Year 6 students recalled more in a Dx than
      in an Mx condition, but there was no significant difference in processing speed
      between conditions. CONCLUSIONS: In both conditions, findings indicate that the
      experts' and Year 4 students' performance was not affected by processing focus.
      The fact that only Year 6 students were affected by processing focus might be
      explained by the assumption that their diagnostic knowledge and management
      knowledge are not fully integrated yet, a process that has already taken place in
      the expert's knowledge structure.

PMID- 18045369
TI  - Science is fundamental: the role of biomedical knowledge in clinical reasoning.
AB  - CONTEXT: Although training in basic science is generally considered a critical
      aspect of medical education, there is little consensus regarding its precise role
      in clinical reasoning. Whereas some reports suggest that biomedical knowledge is
      rarely used in routine diagnosis, other research has found that biomedical
      knowledge can become an integral part of the expert knowledge base. OBJECTIVE:
      The purpose of the current paper is to present evidence in support of different
      views regarding the role of biomedical knowledge, including the two-world
      hypothesis, encapsulation theory and recent work on the role of biomedical
      knowledge in novice diagnosticians. The implications of these models for clinical
      teaching will be examined. DISCUSSION: Recent work suggests that biomedical
      knowledge can help novices develop a coherent and stable mental representation of
      disease categories. As a result, learners are able to retain clinical knowledge
      over time and maintain diagnostic accuracy when faced with clinical challenges.
      This suggests that clinical teachers should attempt to make explicit connections
      between biomedical knowledge and clinical facts during training.

PMID- 18045370
TI  - Scripts and clinical reasoning.
AB  - CONTEXT: Each clinical encounter represents an amazing series of psychological
      events: perceiving the features of the situation; quickly accessing relevant
      hypotheses; checking for signs and symptoms that confirm or rule out competing
      hypotheses, and using related knowledge to guide appropriate investigations and
      treatment. OBJECTIVE: Script theory, issued from cognitive psychology, provides
      explanations of how these events are mentally processed. This essay is aimed at
      clinical teachers who are interested in basic sciences of education. It describes
      the script concept and how it applies in medicine via the concept of the 'illness
      script'. METHODS: Script theory asserts that, to give meaning to a new situation
      in our environment, we use goal-directed knowledge structures adapted to perform
      tasks efficiently. These integrated networks of prior knowledge lead to
      expectations, as well as to inferences and actions. Expectations and actions
      embedded in scripts allow subjects to make predictions about features that may or
      may not be encountered in a situation, to check these features in order to
      adequately interpret (classify) the situation, and to act appropriately.
      CONCLUSIONS: Theory raises questions about how illness scripts develop and are
      refined with clinical experience. It also provides a framework to assist their
      acquisition.

PMID- 18045371
TI  - Breaking down automaticity: case ambiguity and the shift to reflective approaches
      in clinical reasoning.
AB  - CONTEXT: Two modes of case processing have been shown to underlie diagnostic
      judgements: analytical and non-analytical reasoning. An optimal form of clinical
      reasoning is suggested to combine both modes. Conditions leading doctors to shift
      from the usual mode of non-analytical reasoning to reflective reasoning have not
      been identified. This paper reports a study aimed at exploring these conditions
      by investigating the effects of ambiguity of clinical cases on clinical
      reasoning. METHODS: Participants were 16 internal medicine residents in the
      Brazilian state of Ceara. They were asked to diagnose 20 clinical cases and
      recall case information. The independent variable was the degree of ambiguity of
      clinical cases, with 2 levels: straightforward (i.e. non-ambiguous) and
      ambiguous. Dependent variables were processing time, diagnostic accuracy and
      proposition per category recalled. Data were analysed using a repeated measures
      design. RESULTS: Participants processed straightforward cases faster and more
      accurately than ambiguous ones. The proportion of text propositions recalled was
      significantly lower (t[15] = 2.29, P = 0.037) in ambiguous cases, and an
      interaction effect between case version and proposition category was also found
      (F[5, 75] = 4.52, P = 0.001, d = 0.232, observed power = 0.962). Furthermore,
      participants recalled significantly more literal propositions from the ambiguous
      cases than from the straightforward cases (t[15] = 2.28, P = 0.037). CONCLUSIONS:
      Ambiguity of clinical cases was shown to lead residents to switch from automatic
      to reflective reasoning, as indicated by longer processing time, and more literal
      propositions recalled in ambiguous cases.

PMID- 18045372
TI  - Postmortem intubation training: patient and family opinion.
AB  - OBJECTIVE: Endotracheal intubation is a life-saving skill which requires training
      to master. Learning opportunities for endotracheal intubation must be balanced
      with patient rights and intentions. This study was conducted to explore patient
      and family opinions about postmortem endotracheal intubation training. METHODS:
      We carried out an observational, cross-sectional survey study in an urban,
      teaching hospital, on the day of hospital discharge. Subjects were neurologically
      unimpaired neurosurgical patients discharged from hospital in 2004-2005, and
      their relatives. We carried out interviews using a standardised script to
      determine whether subjects would permit postmortem intubation training on
      themselves or relatives, and whether permission should be granted by relatives
      before training. RESULTS: A total of 85% of patient and family respondents would
      allow intubation training after death on themselves, 76% would allow endotracheal
      intubation to be practised on a relative, and 81% felt the deceased's next-of-kin
      should be asked for permission prior to endotracheal intubation training.
      Subjects responded consistently as to what they would allow on self and family.
      Knowledge that the deceased person would have agreed to his or her body being
      used in endotracheal intubation training increased their likelihood of granting
      permission for training (P = 0.008). White subjects were 4.6 times more likely
      than non-Whites to allow intubation training on themselves (P = 0.01).
      CONCLUSIONS: Patients and families are agreeable to postmortem intubation
      training; however, most expect to be asked for permission. Utilising existing
      mechanisms which communicate desired treatment, such as advance directives,
      hospital admissions documents, donor registries or community health fairs may
      facilitate training opportunities and altruistic patient intentions.

PMID- 18045373
TI  - Portfolios in medical education: why do they meet with mixed success? A
      systematic review.
AB  - CONTEXT: The move towards competence-based medical education has created a need
      for instruments that support and assess competence development. Portfolios seem
      suitable but mixed reports of their success are emerging. METHODS: To examine the
      effectiveness of portfolios, we searched PubMed and EMBASE using the keyword
      'portfol*', PsychInfo and ERIC using the keywords 'portfol*' and 'medical
      education' and references of retrieved papers for empirical studies on portfolios
      in all phases of medical education. Thirty of 1939 retrieved papers met the
      inclusion criteria and were analysed. Data were collated against the research
      question, number of subjects, design, setting, findings and limitations, purpose
      and content, mentoring and assessment. We analysed impact using a modified
      version of Kirkpatrick's hierarchy. RESULTS: Because differences across studies
      precluded statistical meta-analysis, the data were analysed by context, goals and
      procedure. Positive effects were strongest in undergraduate education. Important
      factors for success were: clearly communicated goals and procedures; integration
      with curriculum and assessment; flexible structure; support through mentoring,
      and measures to heighten feasibility and reduce required time. Moderately good
      inter-rater reliability was reported and global criteria and discussions among
      raters were beneficial. Formative and summative assessment could be combined.
      Without assessment, portfolios were vulnerable to competition from other
      summative assessment instruments. CONCLUSIONS: For portfolios to be effective in
      supporting and assessing competence development, robust integration into the
      curriculum and tutor support are essential. Further studies should focus on the
      effectiveness and user-friendliness of portfolios, the merits of holistic
      assessment procedures, and the competences of an effective portfolio mentor.

PMID- 18045374
TI  - Is there a relationship between where students sit in lectures and their
      performance in examinations?

PMID- 18045375
TI  - Surgical e-learning: validation of multi-media, web-based lectures.

PMID- 18045377
TI  - The need to improve the teaching of assessment of psychiatric symptoms at
      undergraduate level.

PMID- 18045379
TI  - Indications, outcomes and complications following lateral thoracotomy in dogs and
      cats.
AB  - OBJECTIVES: Lateral thoracotomy is widely used for surgical management of
      thoracic diseases in small animals. The purpose of this paper is to describe the
      indications for lateral thoracotomy in dogs and cats and the associated outcomes
      and complications. METHODS: Medical records of animals undergoing lateral
      thoracotomy were reviewed and owners contacted regarding complications and
      survival. Relationships between signalment and treatment variables and outcome
      variables were investigated. RESULTS: Seventy dogs and 13 cats underwent lateral
      thoracotomy. Sixty-two per cent of cats and 91 per cent of dogs survived to
      discharge. Survival to discharge was significantly lower in cats than dogs, for
      neoplastic than non-neoplastic disease and in older animals. Survival to
      discharge was higher in animals undergoing patent ductus arteriosus ligation than
      in those undergoing lung lobectomy or oesophageal surgery. Survival to discharge
      was not related to surgeon experience. The incidence of complications was not
      related to species, age, disease, duration of surgery, surgeon experience or
      duration of thoracostomy tube placement. A low complication rate (5 per cent) was
      associated with thoracostomy tubes. CLINICAL SIGNIFICANCE: The approach of
      lateral thoracotomy has a minimal complication rate and animals with a disease
      requiring this approach have a high survival rate.

PMID- 18045381
TI  - What is your diagnosis? Emphysematous pyometra with a large amount of gas.

PMID- 18045382
TI  - Novel mitochondrion-related organelles in the anaerobic amoeba Mastigamoeba
      balamuthi.
AB  - Unicellular eukaryotes that lack mitochondria typically contain related
      organelles such as hydrogenosomes or mitosomes. To characterize the evolutionary
      diversity of these organelles, we conducted an expressed sequence tag (EST)
      survey on the free-living amoeba Mastigamoeba balamuthi, a relative of the human
      parasite Entamoeba histolytica. From 19 182 ESTs, we identified 21 putative
      mitochondrial proteins implicated in protein import, amino acid interconversion
      and carbohydrate metabolism, two components of the iron-sulphur cluster (Fe-S)
      assembly apparatus as well as two enzymes characteristic of hydrogenosomes. By
      immunofluorescence microscopy and subcellular fractionation, we show that
      mitochondrial chaperonin 60 is targeted to small abundant organelles within
      Mastigamoeba. In transmission electron micrographs, we identified double
      membraned compartments that likely correspond to these mitochondrion-derived
      organelles, The predicted organellar proteome of the Mastigamoeba organelle
      indicates a unique spectrum of functions that collectively have never been
      observed in mitochondrion-related organelles. However, like Entamoeba, the Fe-S
      cluster assembly proteins in Mastigamoeba were acquired by lateral gene transfer
      from epsilon-proteobacteria and do not possess obvious organellar targeting
      peptides. These data indicate that the loss of classical aerobic mitochondrial
      functions and acquisition of anaerobic enzymes and Fe-S cluster assembly proteins
      occurred in a free-living member of the eukaryote super-kingdom Amoebozoa.

PMID- 18045383
TI  - The crystal structure of staphylococcal superantigen-like protein 11 in complex
      with sialyl Lewis X reveals the mechanism for cell binding and immune inhibition.
AB  - Staphylococcus aureus is a major pathogen that produces a family of 14
      staphylococcal superantigen-like (SSL) proteins, which are structurally similar
      to superantigens but do not stimulate T cells. SSL11 is one member of the family
      that is found in all staphylococcal strains. Recombinant SSL11 bound to
      granulocytes and monocytes through a sialic acid-dependent mechanism and was
      rapidly internalized. SSL11 also bound to sialic acid-containing glycoproteins,
      such as the Fc receptor for IgA (FcalphaRI) and P-selectin glycoprotein ligand-1
      (PSGL-1), and inhibited neutrophil attachment to a P-selectin-coated surface.
      Biosensor analysis of two SSL11 alleles binding to sialyl Lewis X [sLe(x)-
      Neu5Acalpha2-3Galbeta1-4(Fuc1-3)GlcNAc] coupled to bovine serum albumin gave
      dissociation constants of 0.7 and 7 mum respectively. Binding of SSL11 to a
      glycan array revealed specificity for glycans containing the trisaccharide
      sialyllactosamine (sLacNac - Neu5Acalpha2-3Galbeta1-4GlcNAc). A 1.6 A resolution
      crystal structure of SSL11 complexed with sLe(x) revealed a discrete binding site
      in the C-terminal beta-grasp domain, with predominant interactions with the
      sialic acid and galactose residues. A single amino acid mutation in the
      carbohydrate binding site abolished all SSL11 binding. Thus, SSL11 is a
      staphylococcal protein that targets myeloid cells by binding sialyllactosamine
      containing glycoproteins.

PMID- 18045384
TI  - A gene cluster that regulates both heterocyst differentiation and pattern
      formation in Anabaena sp. strain PCC 7120.
AB  - Wild-type Anabaena sp. strain PCC 7120, a filamentous nitrogen-fixing
      cyanobacterium, produces single heterocysts at semi-regular intervals. asr0100
      (patU5) and alr0101 (patU3) are homologous to the 5' and 3' portions of patU of
      Nostoc punctiforme. alr0099 (hetZ) overlaps the 5' end of patU5. hetZ, patU5 and
      patU3 were all upregulated, or expressed specifically, in proheterocysts and
      heterocysts. Mutants of hetZ showed delayed or no heterocyst differentiation. In
      contrast, a patU3 mutation produced a multiple contiguous heterocyst (Mch)
      phenotype and restored the formation of otherwise lost intercalary heterocysts in
      a patA background. Decreasing the expression of patU3 greatly increased the
      frequency of heterocysts in a mini-patS strain. Two promoter regions and two
      principal, corresponding transcripts were detected in the hetZ-patU5-patU3
      region. Transcription of hetZ was upregulated in a hetZ mutant and downregulated
      in a patU3 mutant. When mutants hetZ::C.K2 and hetZ::Tn5-1087b were nitrogen
      deprived, P(hetC)-gfp was very weakly expressed, and in hetZ::Tn5-1087b, P(hetR)
      gfp was relatively strongly expressed in cells that had neither a regular pattern
      nor altered morphology. We conclude that the hetZ-patU5-patU3 cluster plays an
      important role in co-ordination of heterocyst differentiation and pattern
      formation. The presence of homologous clusters in filamentous genera without
      heterocysts is suggestive of a more general role.

PMID- 18045385
TI  - RsaL provides quorum sensing homeostasis and functions as a global regulator of
      gene expression in Pseudomonas aeruginosa.
AB  - The quorum sensing (QS) signalling system of Pseudomonas aeruginosa controls many
      important functions, including virulence. Although the production of the QS
      signal molecule N-3-oxo-dodecanoyl-homoserine lactone (3OC(12)-HSL) is positively
      autoregulated, its concentration reaches a steady level long before stationary
      phase. The RsaL protein represses transcription of the lasI signal synthase gene,
      and thus reduces QS signal production. We show that RsaL binds simultaneously
      with LasR to the rsaL-lasI bidirectional promoter thereby preventing the LasR
      dependent activation of both genes. In an rsaL mutant, 3OC(12)-HSL production
      continues to increase throughout growth. Thus RsaL provides homeostasis by
      functioning in opposition to LasR and limiting 3OC(12)-HSL production to a
      physiological concentration. Furthermore, transcription profiling revealed that
      RsaL regulates 130 genes independent of its effect on QS signal molecule
      production, including genes involved in virulence. We show that RsaL can repress
      pyocyanin and hydrogen cyanide virulence genes in two ways: directly, by binding
      to their promoters, and indirectly, by decreasing levels of the signals for their
      QS signal-dependent transcription. These investigations highlight the importance
      of RsaL as a global regulator of P. aeruginosa physiology that provides a
      counterbalance to 3OC(12)-HSL-dependent gene activation via multiple mechanisms.

PMID- 18045386
TI  - Haloferax volcanii twin-arginine translocation substates include secreted
      soluble, C-terminally anchored and lipoproteins.
AB  - Recent in silico and in vivo studies have suggested that the majority of proteins
      destined for secretion in the haloarchaea are trafficked through the twin
      arginine translocation (Tat) pathway. The presence of lipobox motifs in most
      haloarchaeal Tat signal sequences is intriguing as: (i) bioinformatic searches of
      archaeal genomes have not identified lipoprotein biogenesis enzymes and (ii)
      there are no known Tat substrates containing both a twin-arginine and a bona fide
      lipobox. We have examined six computationally designated Tat substrates in the
      haloarchaeon Haloferax volcanii to verify previous computational predictions and
      to initiate studies of lipoprotein biogenesis via the Tat pathway. Our results
      confirmed that the six candidate proteins were not only Tat substrates, but also
      belonged to diverse classes of secretory proteins. Analysis of predicted
      lipoprotein Tat substrates revealed that they are anchored to the archaeal
      membrane in a cysteine-dependent manner. Interestingly, despite the absence of an
      archaeal lipoprotein signal peptidase II (SPase II) homologue, the SPase II
      inhibitor globomycin impeded cell growth and specifically prevented maturation of
      lipoproteins. Together, this work not only represents the first experimental
      demonstration of a lipoprotein Tat substrate, but also indicates the presence of
      an unidentified lipoprotein biogenesis pathway in archaea.

PMID- 18045387
TI  - The prion/lipid hypothesis--further evidence to support the molecular basis for
      transmissible spongiform encephalopathy risk assessment.
AB  - Defining the molecular structure of the transmissible spongiform encephalopathy
      (TSE) agent is important both for underpinning risk assessments and for
      developing and understanding decontamination strategies. Recent studies have
      shown that oligomeric particles comprising 14-28 prion protein (PrP) molecules
      are much more infectious than larger fibrils (prion rods) or indeed smaller
      oligomers (trimers) and PrP monomers. Here, results from deactivation studies
      (with alkali, heat, hexane or formaldehyde) are interpreted in terms of the
      infectious nucleation seed comprising 14-28 PrP molecules held together by
      interactions with amphipathic phospholipid (PL) or more probably sphingolipid
      (SL) from the host. According to the PrP/lipid hypothesis, the strength of the
      protein/lipid interactions accounts for the high thermostability of TSE
      infectivity and for differences in thermostability between strains. The
      implications of the molecular biophysics data for environmental TSE risk
      assessments are discussed with respect to behaviour in soil. While formaldehyde
      appears to cause inactivation of scrapie infectivity by increasing the ID(50),
      the dose-response is complicated by apparent heterogeneity between hamster
      subpopulations in susceptibility. The process of inactivation by formaldehyde may
      be due to cross-linking the highly infectious 14-28 PrP oligomers into larger,
      but less infectious aggregates. This process appears more reversible in some
      hamster subpopulations than others.

PMID- 18045388
TI  - The application of chromogenic media in clinical microbiology.
AB  - Since 1990, a wide range of chromogenic culture media has been made commercially
      available providing useful tools for diagnostic clinical microbiology. By the
      inclusion of chromogenic enzyme substrates targeting microbial enzymes, such
      media are able to target pathogens with high specificity. Examples of target
      pathogens include Staphylococcus aureus, Streptococcus agalactiae, Salmonella
      spp. and Candida spp. The inclusion of multiple chromogenic substrates into
      culture media facilitates the differentiation of polymicrobial cultures, thus
      allowing for the development of improved media for diagnosis of urinary tract
      infections and media for the enhanced discrimination of yeasts. The purpose of
      this review is to provide some insight into how such media work and appraise
      their utility in routine clinical diagnostics, in comparison with conventional
      media.

PMID- 18045389
TI  - Antimicrobial activity of flavonoids extracted from bergamot (Citrus bergamia
      Risso) peel, a byproduct of the essential oil industry.
AB  - AIMS: To evaluate the antimicrobial properties of flavonoid-rich fractions
      derived from bergamot peel, a byproduct from the Citrus fruit processing industry
      and the influence of enzymatic deglycosylation on their activity against
      different bacteria and yeast. METHODS AND RESULTS: Bergamot ethanolic fractions
      were tested against Gram-negative bacteria (Escherichia coli, Pseudomonas putida,
      Salmonella enterica), Gram-positive bacteria (Listeria innocua, Bacillus
      subtilis, Staphylococcus aureus, Lactococcus lactis) and the yeast Saccharomyces
      cerevisiae. Bergamot fractions were found to be active against all the Gram
      negative bacteria tested, and their antimicrobial potency increased after
      enzymatic deglycosylation. The minimum inhibitory concentrations of the fractions
      and the pure flavonoids, neohesperidin, hesperetin (aglycone), neoeriocitrin,
      eriodictyol (aglycone), naringin and naringenin (aglycone), were found to be in
      the range 200 to 800 microg ml(-1). The interactions between three bergamot
      flavonoids were also evaluated. CONCLUSION: The enzyme preparation Pectinase 62L
      efficiently converted common glycosides into their aglycones from bergamot
      extracts, and this deglycosylation increased the antimicrobial potency of Citrus
      flavonoids. Pairwise combinations of eriodictyol, naringenin and hesperetin
      showed both synergistic and indifferent interactions that were dependent on the
      test indicator organism. SIGNIFICANCE AND IMPACT OF THE STUDY: Bergamot peel is a
      potential source of natural antimicrobials that are active against Gram-negative
      bacteria.

PMID- 18045390
TI  - Ruminococcus bromii, identification and isolation as a dominant community member
      in the rumen of cattle fed a barley diet.
AB  - AIMS: To identify dominant bacteria in grain (barley)-fed cattle for isolation
      and future use to increase the efficiency of starch utilization in these cattle.
      METHODS AND RESULTS: Total DNA was extracted from samples of the rumen contents
      from eight steers fed a barley diet for 9 and 14 days. Bacterial profiles were
      obtained using denaturing gradient gel electrophoresis (DGGE) of the PCR
      amplified V2/V3 region of the 16S rRNA genes from total bacterial DNA. Apparently
      dominant bands were excised and cloned, and the clone insert sequence was
      determined. One of the most common and dominant bacteria present was identified
      as Ruminococcus bromii. This species was subsequently isolated using traditional
      culture-based techniques and its dominance in the grain-fed cattle was confirmed
      using a real-time Taq nuclease assay (TNA) designed for this purpose. In some
      animals, the population of R. bromii reached densities above 10(10)R. bromii cell
      equivalents per ml or approximately 10% of the total bacterial population.
      CONCLUSIONS: Ruminococcus bromii is a dominant bacterial population in the rumen
      of cattle fed a barley-based diet. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Ruminococcus bromii YE282 may be useful as a probiotic inoculant to increase the
      efficiency of starch utilization in barley-fed cattle. The combination of DGGE
      and real-time TNA has been an effective process for identifying and targeting for
      isolation, dominant bacteria in a complex ecosystem.

PMID- 18045391
TI  - Effect of insertional mutations in the pueA and pueB genes encoding two
      polyurethanases in Pseudomonas chlororaphis contained within a gene cluster.
AB  - AIMS: To better understand the role of PueA and PueB from Pseudomonas
      chlororaphis in polyurethane degradation, the present study was conducted to
      create insertional mutants in their respective genes. METHODS AND RESULTS: Growth
      kinetic studies showed that the pueA knockout mutant had a greater effect than
      the pueB knockout mutant. The pueA mutant had an 80% decrease in cell density
      from that of the wild type, while the pueB mutant had an 18% decrease in cell
      density. Polyurethane utilization followed Michaelis-Menten kinetics. The pueA
      and pueB mutants exhibited a 17% and 10% decrease respectively in growth rate
      using polyurethane when compared with the wild type. CONCLUSIONS: In this present
      study, pueA and pueB, are shown to be part of an ABC transporter gene cluster
      that consists of seven open reading frames. Mutational analysis results suggest
      that PueA may play a more major role in polyurethane degradation than PueB based
      on cell density and growth rates. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      results from this study provide a starting point for the eventual enhancement and
      bioremediation of polyurethane waste. Understanding the role of polyurethane
      degrading enzymes is useful for the creation of strains for this purpose.

PMID- 18045392
TI  - Production of recombinant human erythropoietin from Pichia pastoris and its
      structural analysis.
AB  - AIMS: To design and investigate a recombinant expression system producing a
      therapeutically important glycoprotein, human erythropoietin (rHuEPO), by Pichia
      pastoris. METHODS AND RESULTS: EPO cDNA was cloned into pPICZalphaA for
      expression under control of AOX1 promoter and fused, on the amino-terminal end,
      with a polyhistidine tag for rapid purification. A target site for factor Xa
      protease was also introduced, such that cleavage in vitro produced a mature form
      of rHuEPO having the native N- and C-termini. RHuEPO was characterized as to the
      extent and nature of N-linked glycosylation using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and western blotting. The
      rHuEPO produced was approximately 30 kDa. All three N-linked glycosylation sites
      were occupied dominantly by Man(17)(GlcNAc)(2). N-glycanase-treated rHuEPO
      purified but not digested with factor-Xa-protease, showed a spectral peak
      centered about m/z 20400 Da. CONCLUSIONS: The native polypeptide form of human
      EPO (c. 18 kDa) was obtained for the first time in P. pastoris expression system,
      after affinity purification, deglycosylation and factor-Xa-protease digestion.
      The amount of sodium dodecyl sulfate used prior to deglycosylation was found to
      be crucial in determining the dominant form of glycan in glycoproteins.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The novel approaches to protein expression
      and purification system and structural analysis presented, would be important
      especially for therapeutic proteins expressed in P. pastoris.

PMID- 18045393
TI  - Orthogonal array design in optimizing ERIC-PCR system for fingerprinting rat's
      intestinal microflora.
AB  - AIMS: The aim of the present study was to rapidly optimize enterobacterial
      repetitive intergenic consensus (ERIC)-PCR amplification systems for
      fingerprinting rat's intestinal microflora. METHODS AND RESULTS: Orthogonal array
      design and statistic analysis methods were attempted to rapidly optimize ERIC-PCR
      reaction system for fingerprinting intestinal microflora. The results showed that
      variations of the four factors (Mg(2+), dNTP, primer and HotstarTaq polymerase
      concentrations) changed the fingerprinting patterns significantly. The order of
      effects of those factors on fingerprinting patterns was primers (F = 274.000, P =
      0.000), Hotstar Taq polymerase (F = 197.000, P = 0.001), Mg(2+) (F = 181.000, P =
      0.001) and dNTP (F = 27.000, P = 0.011). The optimal ERIC-PCR condition was
      containing 200 micromol l(-1) dNTP, 2.5 mmol l(-1) Mg(2+), 0.4 micromol l(-1)
      primer, 1 U HotstarTaq DNA polymerase namely 25 microl reaction system, which is
      proved to be a simple, fast and reliable method suitable for fingerprinting rat's
      intestinal microflora. CONCLUSIONS: The results suggest that Mg(2+), dNTP, primer
      and HotstarTaq polymerase concentrations play important roles on ERIC-PCR
      fingerprinting patterns. Orthogonal array design is a considerable method to
      optimize ERIC-PCR reaction system for its rapidness, simplicity, potential to
      investigate mutual effects of parameters. SIGNIFICANCE AND IMPACT OF THE STUDY:
      It is the first report on optimization of ERIC-PCR amplification systems for
      fingerprinting intestinal microflora using orthogonal array design or statistic
      analysis methods and systematically observing the effects of variables of
      reaction conditions.

PMID- 18045394
TI  - A rapid monitoring assay for the detection of Salmonella spp. and Salmonella
      Senftenberg strain W775 in composts.
AB  - AIMS: The composting process needs to be validated for its hygienic status in
      order to ensure that it is free of pathogens. Generally, this is evaluated
      through temperature monitoring, or additionally through active inoculation and
      monitoring of indicator organisms. We aimed to develop a monitoring method for
      the heat-resistant indicator organism Salmonella enterica ssp. enterica serovar
      Senftenberg strain W775 for detection in composting biowastes. METHODS AND
      RESULTS: The method development is comprised of: (i) optimization of molecular
      detection of bacteria belonging to the genus Salmonella; (ii) identification of a
      DNA marker for Salmonella strain W775; and (iii) development of a multiplex
      polymerase chain reaction (PCR)-based on both DNA markers. Subsequently,
      Salmonella strain W775 was inoculated and monitored during composting of
      biowastes in an industrial composting facility. CONCLUSIONS: A highly sensitive
      and specific detection of viable cells was obtained by enriching the compost
      sample prior to multiplex PCR analysis. Complete inactivation of Salmonella
      strain W775 was obtained within 4 days in an industrial composting facility at
      temperatures ranging between 41 and 57 degrees C. SIGNIFICANCE AND IMPACT OF THE
      STUDY: We describe a monitoring method for the simultaneous detection of
      naturally occurring Salmonella strains and artificially introduced Salmonella
      strain W775 in composting biowastes that can be applied in routine analysis.

PMID- 18045395
TI  - Statistical comparison of Campylobacter jejuni subtypes from human cases and
      environmental sources.
AB  - AIM: To analyse Campylobacter jejuni typing data to define statistically which
      potential reservoirs and transmission sources contain isolates that are most
      similar to one another and to isolates from human infections. METHODS AND
      RESULTS: Serotyping and SmaI macrorestriction profiling data for C. jejuni
      isolates from human campylobacteriosis cases, chicken carcass rinses, duck,
      sheep, dairy and beef cattle faeces, river water, and sheep, beef and pork offal
      obtained from a defined rural area of New Zealand were compared using the
      Czekanowski proportional similarity index. Subtypes of isolates from ruminant
      animals, whether derived from their faeces or offals, were generally similar to
      one another. The spectrum of isolate subtypes from human cases was more similar
      to that from ruminant faeces than the other matrices considered. Isolate subtypes
      from chicken rinses, pork offal, water and duck faeces were not highly similar to
      those from other matrices. CONCLUSIONS: Results from a combination of phenotypic
      and genotypic approaches suggest that, for this rural population, exposures
      associated with a rural lifestyle may be significant sources of human
      campylobacteriosis. SIGNIFICANCE AND IMPACT OF THE STUDY: The Czekanowski index
      was applied to subtyping data and supported the greater importance of contact
      with livestock in campylobacteriosis cases associated with a rural setting, in
      comparison with urban studies that have identified poultry-related factors.

PMID- 18045396
TI  - Effect of a blend of essential oil compounds on the colonization of starch-rich
      substrates by bacteria in the rumen.
AB  - AIMS: To investigate the mode of action of a blend of essential oil compounds on
      the colonization of starch-rich substrates by rumen bacteria. METHODS AND
      RESULTS: Starch-rich substrates were incubated, in nylon bags, in the rumen of
      sheep organized in a 4 x 4 latin square design and receiving a 60:40 silage :
      concentrate diet. The concentrate was either high or low in crude protein, and
      the diet was supplemented or not with a commercial blend of essential oil
      compounds (110 mg per day). The total genomic DNA was extracted from the residues
      in the bags. The total eubacterial DNA was quantified by real-time PCR and the
      proportion of Ruminobacter amylophilus, Streptococcus bovis and Prevotella
      bryantii was determined. Neither the supplementation with essential oil compounds
      nor the amount of crude protein affected the colonization of the substrates by
      the bacteria quantified. However, colonization was significantly affected by the
      substrate colonized. CONCLUSIONS: The effect of essential oils on the
      colonization of starch-rich substrates is not mediated through the selective
      inhibition of R. amylophilus. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      enhances our understanding of the colonization of starch-rich substrates, as well
      as of the mode of action of the essential oils as rumen manipulating agents.

PMID- 18045397
TI  - Preliminary characterization of lactic acid bacteria isolated from Zlatar cheese.
AB  - AIMS: Isolation, characterization and identification of lactic acid bacteria
      (LAB) from artisanal Zlatar cheese during the ripening process and selection of
      strains with good technological characteristics. METHODS AND RESULTS:
      Characterization of LAB was performed based on morphological, physiological and
      biochemical assays, as well as, by determining proteolytic activity and plasmid
      profile. rep-polymerase chain reaction (PCR) analysis and 16S rDNA sequencing
      were used for the identification of LAB. PCR analysis was performed with specific
      primers for detection of the gene encoding nisin production. Strains
      Lactobacillus paracasei subsp. paracasei, Lactobacillus plantarum, Lactobacillus
      brevis, Lactococcus lactis subsp. lactis, Enterococcus faecium and Enterococcus
      faecalis were the main groups present in the Zlatar cheese during ripening.
      CONCLUSIONS: Temporal changes in the species were observed during the Zlatar
      cheese ripening. Mesophilic lactobacilli are predominant microflora in Zlatar
      cheese. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study we determined that
      Zlatar cheese up to 30 days old could be used as a source of strains for the
      preparation of potential starter cultures in the process of industrial cheese
      production. As the Serbian food market is adjusting to European Union
      regulations, the standardization of Zlatar cheese production by using starter
      culture(s) based on autochtonous well-characterized LAB will enable the
      industrial production of this popular cheese in the future.

PMID- 18045398
TI  - Quantitative analysis of human enteric adenoviruses in aquatic environments.
AB  - AIMS: The aim of this study was to determine human adenoviruses (HuAdVs) in
      aquatic environments by real-time polymerase chain reaction (PCR). METHODS AND
      RESULTS: In order to describe the ratio of enteric serotypes to the total HuAdVs,
      the primer set specific for the enteric serotypes 40 and 41 was used in parallel
      with the universal primer set for all 51 serotypes of HuAdVs. The enteric
      serotypes of HuAdVs were detected at the concentration of 7.3-1500 PCR-detection
      units (PDU) per ml in raw sewage (n = 17), 0.00060-4.1 PDU ml(-1) in secondary
      treated sewage before chlorination (n = 17), 0.0018-7.0 PDU ml(-1) in river water
      (n = 36), and 0.032-6.1 PDU ml(-1) in seawater (n = 18). The concentration of
      HuAdVs, determined by the universal primer set, was equivalent to that of enteric
      serotypes in almost all the samples tested. CONCLUSIONS: Enteric serotypes were
      predominant among all serotypes of HuAdVs in the aquatic environments.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The abundance of enteric serotypes of
      HuAdVs should be more emphasized than other serotypes in order to assess the risk
      of their infection via water.

PMID- 18045399
TI  - Characterization of dehydromonacolin-MV2 from Monascus purpureus mutant.
AB  - AIM: Characterization of dehydromonacolin-MV2, a bioactive metabolite isolated
      from Monascus purpureus mutant (CFR 410-11). METHODS AND RESULTS: Chloroform
      extract of rice, fermented with a hyperpigment-producing mutant of M. purpureus
      (CFR 410-11) was found to contain metabolites that inhibited the growth of
      Bacillus, Pseudomonas and Streptococcus in agar gel diffusion assays. The extract
      inhibited lipid peroxidation and scavenged 2,2-diphenyl-1-pycrylhydrazyl and
      hydroxyl radicals. The active compound purified by silica gel column
      chromatography was characterized by NMR. The carbon, proton and 2D HSQCT
      assignments identified dehydromonacolin-MV2 as the bioactive metabolite.
      CONCLUSIONS: Dehydromonacolin-MV2 apparently originated in the mutant by
      hydroxylation and oxidation of monacolin-J, an intermediate of monacolin
      biosynthetic pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: Identification of the
      production of dehydromonacolin-MV2 by M. purpureus mutant (CFR 410-11) is new to
      literature. Bioactive properties of the compound suggested its pharmaceutical
      applications.

PMID- 18045400
TI  - Regulation of alkaline metalloprotease promoter by N-acyl homoserine lactone
      quorum sensing in Pseudomonas fluorescens.
AB  - AIMS: To examine the involvement of N-acyl homoserine lactone (AHL) quorum
      sensing in alkaline metalloprotease (aprX) promoter regulation in a Pseudomonas
      fluorescens milk isolate. METHODS AND RESULTS: N-acyl homoserine lactone signals
      from P. fluorescens strain 395 were separated and detected by thin layer
      chromatography (TLC). Further analysis of the AHL signals using liquid
      chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) indicated
      the presence of C4-HSL and 3OC8-HSL. The expression of aprX in P. fluorescens 395
      was investigated, using a transcriptional fusion between the aprX promoter and a
      mutated gfp variant gene (gfp[mut3]). The results demonstrated that the activity
      of the aprX promoter increased dramatically in the late exponential phase of
      growth, indicating growth phase-dependent regulation. The activity was repressed
      in an AHL-deficient environment, in which the signal molecules were hydrolysed by
      the enzyme AHL lactonase. CONCLUSIONS: N-acyl homoserine lactones produced by P.
      fluorescens 395 were identified to be C4-HSL and 3OC8-HSL. The protease gene in
      P. fluorescens is regulated by the AHL-based quorum sensing system at a
      transcriptional level during the late exponential growth phase. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study contributes to our understanding of the genetic
      regulation and ecology of P. fluorescens in the economically important system of
      food spoilage.

PMID- 18045402
TI  - Production of cellulases and hemicellulases by Penicillium echinulatum grown on
      pretreated sugar cane bagasse and wheat bran in solid-state fermentation.
AB  - AIM: To evaluate the solid-state fermentation (SSF) production of cellulase and
      hemicellulases (xylanases), by Penicillium echinulatum 9A02S1, in experiments
      carried out with different concentrations of the pretreated sugar cane bagasse
      (PSCB) and wheat bran (WB). METHODS AND RESULTS: This study reports the
      production of xylanolytic and cellulolytic enzymes by P. echinulatum 9A02S1 using
      a cheap medium containing PSCB and WB under SSF. The highest amounts of filter
      paper activity (FPA) could be measured on mixtures of PSCB and WB (32.89 +/- 1.90
      U gdm(-1)). The highest beta-glucosidase activity was 58.95 +/- 2.58 U gdm(-1) on
      the fourth day. The highest activity for endoglucanases was 282.36 +/- 1.23 U
      gdm(-1) on the fourth day, and for xylanases the activity was around 10 U gdm(-1)
      from the second to the fourth day. CONCLUSIONS: The present work has established
      the potential of P. echinulatum for FPA, endoglucanase, beta-glucosidase and
      xylanase productions in SSF, indicating that WB may be partially substituted by
      PSCB. SIGNIFICANCE AND IMPACT OF THE STUDY: The incorporation of cheap sources,
      such as sugar cane bagasse, into media for the production of lignocellulose
      enzymes should help decrease the production costs of enzymatic complexes that can
      hydrolyse lignocellulose residues for the formation of fermented syrups, thus
      contributing to the economic production of bioethanol.

PMID- 18045401
TI  - High degree of correlation between molecular polymorphism and geographic origin
      of wine yeast strains.
AB  - AIMS: To guarantee the endemic genetic background of the isolates obtained in
      yeast isolation programs, it is necessary to differentiate between endemic and
      commercial strains because the progressive use of commercial yeast in wine areas
      around the world would affect the autochthonous yeast populations. METHODS AND
      RESULTS: Mitochondrial DNA restriction analysis, electrophoretic karyotyping and
      random amplification of polymorphic DNA (RAPD) were evaluated as experimental
      approaches to correlate genomic polymorphism and geographic origin of native wine
      yeast strains. The three molecular methods were capable of detecting a European
      commercial strain among native Chilean strains; however, RAPD proved to have the
      best performance. CONCLUSIONS: The molecular polymorphism analysis is useful to
      evaluate the geographical origin of native yeast isolates and confirms or refutes
      the genetic background of currently marketed strains. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This study permits a genetic characterization of native yeast
      populations and confirms its utility as a tool for evaluating if a native isolate
      derives from the region where it was collected, permitting, furthermore, to
      develop studies on the evolution of native yeast populations and to evaluate the
      effect of introduced yeasts on these populations.

PMID- 18045403
TI  - Purification and characterization of a milk-clotting protease from Bacillus
      licheniformis strain USC13.
AB  - AIM: The study of a milk-clotting protease secreted by Bacillus licheniformis
      strain USC13. METHODS AND RESULTS: Growth of B. licheniformis USC13 in LB medium
      resulted in the production of a serine protease with a molecular weight of 62 kDa
      processed to its mature form of 34 kDa, both forms were found in the
      extracellular medium. The enzyme exhibited typical milk-clotting kinetics.
      CONCLUSIONS: The capacity of this protease to produce milk curds could make it
      useful as a new source of milk coagulants. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Cheese-making industry seeks for novel enzyme sources, and microbial coagulants
      have several advantages over animal and plant counterparts. The protease from B.
      licheniformis has the ability to produce milk curds although more studies about
      quality of both the enzyme and the milk curds formed should be carried out in the
      future to confirm its usefulness in the dairy industry.

PMID- 18045404
TI  - Characterization and functional analysis of a novel gene cluster involved in
      biphenyl degradation in Rhodococcus sp. strain R04.
AB  - AIMS: Isolation of the genes relative to PCB biodegradation and identification of
      the bph gene function in Rhodococcus sp. R04. METHODS AND RESULTS: A 8.7-kb
      fragment carrying the biphenyl catabolic genes bphABCD was isolated from the gene
      library in Rhodococcus sp. R04. Based on the deduced amino acid sequence
      homology, seven bph genes, bphA1A2A3A4, bphB, bphC and bphD, were thought to be
      responsible for the initial four steps of biphenyl degradation. In Escherichia
      coli, BphA exhibited poor activity for biphenyl transformation, and BphB, BphC
      and BphD were found to be catalytically active towards 2,3-dihydro-2,3
      dihydroxybiphenyl, 2,3-dihydroxybiphenyl and 2-hydroxy-6-oxo-6-phenylhexa-2,4
      dienoate, respectively (activities of 50, 8.1 and 2.4 micromol l(-1) min(-1) mg(
      1)). SDS-PAGE analysis indicated that the sizes of bphA1A2A3A4, bphB, bphC and
      bphD gene products were 49, 19, 14, 47, 32, 30 and 31 kDa, respectively. After
      disruption of bph genes, the bphA1 mutants lost the ability to grow on biphenyl,
      the bphB and bphD mutants were able to transform a little of biphenyl, but hardly
      grew on biphenyl. CONCLUSION: The cloned bph genes indeed play an important role
      in the biphenyl catabolism in this strain. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This bph gene organization in Rhodococcus sp. R04 differs from that of other
      biphenyl degraders reported previously, indicating it is a novel type of bph gene
      cluster. Analysis of the phylogenetic tree suggested that BphA1 and BphA2 in
      Rhodococcus sp. R04 had a different evolutionary relationship with those in the
      other PCB degraders.

PMID- 18045405
TI  - Inactivation of hepatitis A HM-175/18f, reovirus T1 Lang and MS2 during alkaline
      stabilization of human biosolids.
AB  - AIM: To compare the inactivation rates of male-specific bacteriophage-2 (MS2),
      hepatitis A HM-175/18f (HM-175) and reovirus T1 Lang (T1 L) during alkaline
      stabilization of wastewater residues. METHODS AND RESULTS: A bench scale alkaline
      stabilization model was used to evaluate the inactivation of MS2 seeded into raw
      sludge simultaneously with HM-175 or T1 L. Stabilization was performed in
      triplicate at 28 and 4 degrees C for both viral combinations. During
      stabilization at 28 and 4 degrees C, MS2 and T1 L concentrations were similar at
      each time point (t = 0.1, 2, 12 and 24 h). MS2 and HM-175 concentrations were
      also similar at each time point during stabilization at 28 degrees C. At 4
      degrees C, MS2 and HM-175 concentrations were not similar at the first two time
      points (t = 0.1 and 2 h), but were similar at later time points (t = 12 and 24
      h). CONCLUSIONS: The inactivation rates of T1 L at 4 degrees C and both T1 L and
      HM-175 at 28 degrees C were similar to the inactivation rate of MS2 at all time
      points. At 4 degrees C, MS2 was inactivated at a faster rate during the first two
      time points (t = 0.1 and 2 h) than HM-175, but was inactivated similarly at later
      time points (t = 12 and 24 h). SIGNIFICANCE AND IMPACT OF THE STUDY: Phages, such
      as MS2, would be ideal indicators for the presence of enteric viruses in
      wastewater residues because of their ubiquity, nonpathogenic nature, low cost and
      time associated with their detection. The findings of this study suggest that MS2
      could serve as an indicator for monitoring the persistence of enteric viruses,
      such as HM-175 and T1 L, during alkaline stabilization performed at moderate
      temperatures (28 degrees C), but may not serve as an indicator for HM-175 at
      reduced temperature (4 degrees C). The utility of MS2 as an indicator of viral
      persistence during biosolids treatment should be further evaluated, as the
      increased efficiency and frequency of pathogen monitoring associated with their
      use may reduce the potential public health risk associated with biosolids,
      facilitating a greater acceptance for their land application.

PMID- 18045406
TI  - Efficacy of natamycin for control of growth and ochratoxin A production by
      Aspergillus carbonarius strains under different environmental conditions.
AB  - AIMS: To examine the efficacy of natamycin produced by Streptomyces natalensis
      against strains of Aspergillus carbonarius growth and ochratoxin A (OTA)
      production under different environmental factors on a grape juice-based medium.
      METHODS AND RESULTS: Detailed studies in the range 0-20 ng ml(-1) for control of
      growth and ochratoxin production by strains of A. carbonarius at 0.98, 0.96 and
      0.94 water availabilities (a(w)) and 15-25 degrees C on a fresh red grape extract
      medium were examined. Inhibition of growth was depending on temperature and a(w)
      level. At 15 degrees C, 5-10 ng ml(-1) natamycin was effective in reducing growth
      almost completely. However, at 20-25 degrees C and all the three a(w) levels,
      growth was only slightly inhibited by 5-10 ng ml(-1) natamycin. There were strain
      differences with regard to inhibition of OTA production. At 15 degrees C and 0.98
      a(w), 10 ng ml(-1) was required to inhibit production by >90%. However, at 0.96
      and 0.94 a(w), almost complete inhibition occurred. At 20 degrees C, OTA
      production was only significantly inhibited by 10 ng ml(-1) natamycin at 0.94
      a(w). At 0.96 and 0.98 a(w), some inhibition occurred with 5-10 ng ml(-1), but
      greater concentrations would be required for effective inhibition. At 25 degrees
      C, 5 ng ml(-1) was effective at all a(w) levels. However, at 15 degrees C and 25
      degrees C and a wide range of a(w) levels, natamycin effectively controlled OTA
      production. CONCLUSIONS: Natamycin appears to be a very effective for controlling
      growth and OTA production by strains of A. carbonarius over a range of a(w) and
      temperature conditions on grape-based media. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This is the first detailed study to demonstrate the impact of natamycin
      against A. carbonarius. This study suggests that use of natamycin at 50-100 ng
      ml(-1) can give complete inhibition of growth of A. carbonarius and OTA
      production over a range of environmental conditions. Natamycin could be an
      important component of a system to prevent OTA contamination of wine as well
      during the drying and production of vine fruits.

PMID- 18045407
TI  - Desorption of zinc by extracellularly produced metabolites of Trichoderma
      harzianum, Trichoderma reesei and Coriolus versicolor.
AB  - AIMS: To determine the role of fungal metabolites in the desorption of metals.
      METHODS AND RESULTS: Desorption of Zn from charcoal by three different fungi was
      compared against metal desorption with reverse osmosis water, a 0.1% Tween 80
      solution and a 0.1 mol l(-1) CaCl(2) solution. All three fungal filtrates
      desorbed three times more Zn than either 0.1% Tween 80 or 0.1 mol l(-1) CaCl(2).
      Metal chelator production in Trichoderma harzianum and Coriolus versicolor was
      constitutively expressed while chelator production in Trichoderma reesei was
      induced by Zn. The presence of Zn inhibited the production of metal chelators by
      C. versicolor. Only C. versicolor was found to produce oxalic acid (a strong
      metal chelator). All fungi caused a marked decrease in pH, although this was not
      enough to explain the increased desorption of the metals by the different fungal
      filtrates. CONCLUSIONS: Metal chelation via organic acids and proteins are the
      main mechanisms by which the fungal filtrates increase zinc desorption.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study explain why
      plants inoculated with T. harzianum T22 take up more metal from soil, than
      noninoculated plants while metabolites produced by fungi could be used for metal
      leaching from contaminated soils.

PMID- 18045408
TI  - The heterologous expression of polysaccharidase-encoding genes with oenological
      relevance in Saccharomyces cerevisiae.
AB  - AIMS: The main objective of this study was to develop polysaccharide-degrading
      wine strains of Saccharomyces cerevisiae, which are able to improve aspects of
      wine processing and clarification, as well as colour extraction and stabilization
      during winemaking. METHODS AND RESULTS: Two yeast expression/secretion gene
      cassettes were constructed, namely (i) a pectinase gene cassette (pPPK)
      consisting of the endo-polygalacturonase gene (pelE) from Erwinia chrysanthemi
      and the pectate lyase gene (peh1) from Erwinia carotovora and (ii) a
      glucanase/xylanase gene cassette (pEXS) containing the endo-beta-1,4-glucanase
      gene (end1) from Butyrivibrio fibrisolvens and the endo-beta-1,4-xylanase gene
      (xynC) from Aspergillus niger. The commercial wine yeast strain, VIN13, was
      transformed separately with these two gene cassettes and checked for the
      production of pectinase, glucanase and xylanase activities. Pinot Noir, Cinsaut
      and Muscat d'Alexandria grape juices were fermented using the VIN13[pPPK]
      pectinase- and the VIN13[pEXS] glucanase/xylanase-producing transformants.
      Chemical analyses of the resultant wines indicated that (i) the pectinase
      producing strain caused a decrease in the concentration of phenolic compounds in
      Pinot Noir whereas the glucanase/xylanase-producing strain caused an increase in
      phenolic compounds presumably because of the degradation of the grape skins; (ii)
      the glucanase/xylanase-producing strain caused a decrease in wine turbidity,
      especially in Pinot Noir wine, as well as a clear increase in colour intensity
      and (iii) in the Muscat d'Alexandria and Cinsaut wines, the differences between
      the control wines (fermented with the untransformed VIN3 strain) and the wines
      produced by the two transformed strains were less prominent showing that the
      effect of these polysaccharide-degrading enzymes is cultivar-dependent.
      CONCLUSIONS: The recombinant wine yeasts producing pectinase, glucanase and
      xylanase activities during the fermentation of Pinot Noir, Cinsaut and Muscat
      d'Alexandria grape juice altered the chemical composition of the resultant wines
      in a way that such yeasts could potentially be used to improve the clarity,
      colour intensity and stability and aroma of wine. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Aspects of commercial-scale wine processing and clarification, colour
      extraction and stabilization, and aroma enhancement could potentially be improved
      by the use of polysaccharide-degrading wine yeasts without the addition of
      expensive commercial enzyme preparations. This offers the potential to further
      improve the price:quality ratio of wine according to consumer expectations.

PMID- 18045409
TI  - Characterization of the cellulolytic and hydrogen-producing activities of six
      mesophilic Clostridium species.
AB  - AIMS: To characterize cellulolytic, hydrogen-producing clostridia on a comparable
      basis. METHODS AND RESULTS: H(2) production from cellulose by six mesophilic
      clostridia was characterized in standardized batch experiments using MN301
      cellulose, Avicel and cellobiose. Daily H(2) production, substrate degradation,
      biomass production and the end-point distribution of soluble fermentation
      products varied with species and substrates. All species produced a significant
      amount of H(2) from cellobiose, with Clostridium acetobutylicum achieving the
      highest H(2) yield of 2.3 mol H(2) mol(-1) hexose, but it did not degrade
      cellulose. Clostridium cellulolyticum and Clostridium populeti catalysed the
      highest H(2) production from cellulose, with yields of 1.7 and 1.6 mol H(2 )mol(
      1) hexose from MN301 and 1.6 and 1.4 mol H(2) mol(-1) hexose from Avicel,
      respectively. These species also achieved 25-100% higher H(2) production rates
      from cellulose than the other species. CONCLUSIONS: These cellulolytic, hydrogen
      producing clostridia varied in H(2) production, with Cl. cellulolyticum and Cl.
      populeti achieving the highest H(2) yields and cellulose degradation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The fermentation of cellulosic materials
      presents a means of H(2) production from renewable resources. This standardized
      comparison provides a quantitative baseline for improving H(2) production from
      cellulose through medium and process optimization and metabolic engineering.

PMID- 18045410
TI  - Modelling the effect of temperature and water activity on the growth of two
      ochratoxigenic strains of Aspergillus carbonarius from Greek wine grapes.
AB  - AIMS: To develop descriptive models for the combined effect of temperature (10-40
      degrees C) and water activity (0.850-0.980) on the growth of two ochratoxin A
      producing strains of Aspergillus carbonarius from Greek wine grapes on a
      synthetic grape juice medium. METHODS AND RESULTS: Fungal growth was measured as
      changes in colony diameter on a daily basis. The maximum specific colony growth
      rates (mu(max)) were determined by fitting the primary model of Baranyi
      describing the change in colony diameter (mm) with respect to time (days).
      Secondary models, relating mu(max) with temperature and a(w) were developed and
      comparatively evaluated based on polynomial, Parra, Miles, Davey and Rosso
      equations. No growth was observed at 0.850 a(w) (water activity) regardless of
      temperature, as well as at marginal temperature levels assayed (10 and 40 degrees
      C) regardless of water activity. The data set was fitted successfully in all
      models as indicated by the values of regression coefficients and root mean square
      error. Models with biological interpretable parameters were highly rated compared
      with the polynomial model, providing realistic cardinal values for temperature
      and a(w). The optimum values for growth were found in the range 0.960-0.970 a(w)
      and 34-35 degrees C respectively for both strains. The developed models were
      validated on independently derived data from the literature and presented
      reasonably good predictions as inferred by graphical plots and statistical
      indices (bias and accuracy factors). CONCLUSIONS: The effect of temperature and
      a(w) on the growth of A. carbonarius strains could be satisfactorily predicted
      under the current experimental conditions, and the proposed models could serve as
      a tool for this purpose. SIGNIFICANCE AND IMPACT OF THE STUDY: The results could
      be successfully employed as an empirical approach in the development and
      prediction of risk models of contamination of grapes and grape products by A.
      carbonarius.

PMID- 18045411
TI  - Cloning of a gene encoding thermostable glucoamylase from Chaetomium thermophilum
      and its expression in Pichia pastoris.
AB  - AIMS: Chaetomium thermophilum is a soil-borne thermophilic fungus whose molecular
      biology is poorly understood. Only a few genes have been cloned from the
      Chaetomium genus. This study attempted to clone, to sequence and to express a
      thermostable glucoamylase gene of C. thermophilum. METHODS AND RESULTS: First
      strand cDNA was prepared from total RNA isolated from C. thermophilum and the
      glucoamylase gene amplified by using PCR. Degenerate primers based on the N
      terminal sequences of the purified glucoamylase according to our previous works
      and a cDNA fragment encoding the glucoamylase gene was obtained through RT-PCR.
      Using RACE-PCR, full-length cDNA of glucoamylase gene was cloned from C.
      thermophilum. The full-length cDNA of the glucoamylase was 2016 bp and contained
      a 1797-bp open reading frame encoding a protein glucoamylase precursor of 599
      amino acid residues. The amino-acid sequence from 31 to 45 corresponded to the N
      terminal sequence of the purified protein. The first 30 amino acids were presumed
      to be a signal peptide. The alignment results of the putative amino acid sequence
      showed the catalytic domain of the glucoamylase was high homology with the
      catalytic domains of the other glucoamylases. The C. thermophilum glucoamylase
      gene was expressed in Pichia pastoris, and the glucoamylase was secreted into the
      culture medium by the yeast in a functionally active form. The recombinant
      glucoamylase purified was a glycoprotein with a size of about 66 kDa, and
      exhibited optimum catalytic activity at pH 4.5-5.0 and 65 degrees C. The enzyme
      was stable at 60 degrees C, the enzyme activity kept 80% after 60 min incubation
      at 70 degrees C. The half-life was 40 and 10 min under incubation at 80 and 90
      degrees C respectively. CONCLUSIONS: A new thermostable glucoamylase gene of C.
      thermophilum was cloned, sequenced, overexpressed successfully in P. pastoris.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Because of its thermostability and
      overexpression, this glucoamylase enzyme offers an interesting potential in
      saccharification steps in both starch enzymatic conversion and in alcohol
      production.

PMID- 18045412
TI  - Comparison of the inactivation of Bacillus subtilis spores and MS2 bacteriophage
      by MIOX, ClorTec and hypochlorite.
AB  - AIMS: To compare the disinfection ability of two widely used electrolytic
      generation systems (ClorTec and MIOX) and the conventional chlorine disinfectant
      (sodium hypochlorite) using three strains of Bacillus subtilis spores and MS2
      bacteriophage. METHODS AND RESULTS: Three B. subtilis aerobic spore strains
      (ATCC1A1, 35021 and 35946) and the bacteriophage MS2 (ATCC 15597-B1) were
      propagated and sporulated. Four indicator organisms were exposed to four
      disinfectant treatments for comparing the effectiveness of inactivation:
      hypochlorite, ClorTec, MIOX and MIOX-anode. The results indicated that the two
      electrolytic generation systems were as effective as the conventional
      chlorination for the inactivation of micro-organisms used. Some data points
      showed the variation using anova analysis, in which the inactivation of MIOX and
      ClorTec was higher than that of hypochlorite. CONCLUSIONS: The ClorTec and MIOX
      systems are quite similar to hypochlorite in the inactivation-effectiveness for
      aerobic spores and bacteriophage in drinking water. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Laboratory-scale investigation proved that gaseous chlorine could be
      replaced by either ClorTec or MIOX systems for the drinking water treatment
      utilities, which still could maintain the same disinfection efficiency.

PMID- 18045413
TI  - New water disinfection system using UVA light-emitting diodes.
AB  - AIM: To evaluate the ability of high-energy ultraviolet A (UVA) light-emitting
      diode (LED) to inactivate bacteria in water and investigate the inactivating
      mechanism of UVA irradiation. METHODS AND RESULTS: We developed a new
      disinfection device equipped with high-energy UVA-LED. Inactivation of bacteria
      was determined by colony-forming assay. Vibrio parahaemolyticus, enteropathogenic
      Escherichia coli, Staphylococcus aureus and Escherichia coli DH5alpha were
      reduced by greater than 5-log(10) stages within 75 min at 315 J cm(-2) of UVA.
      Salmonella enteritidis was reduced greater than 4-log(10) stages within 160 min
      at 672 J cm(-2) of UVA. The formation of 8-hydroxy-2'-deoxyguanosine in UVA-LED
      irradiated bacteria was 2.6-fold higher than that of UVC-irradiated bacteria at
      the same inactivation level. Addition of mannitol, a scavenger of hydroxyl
      radicals (OH(*)), or catalase, an enzyme scavenging hydrogen peroxide (H(2)O(2))
      to bacterial suspensions significantly suppressed disinfection effect of UVA-LED.
      CONCLUSION: This disinfection system has enough ability to inactivate bacteria
      and OH(*) and H(2)O(2) participates in the disinfection mechanism of UVA
      irradiation. SIGNIFICANCE AND IMPACT OF THE STUDY: We newly developed UVA
      irradiation system and found that UVA alone was able to disinfect the water
      efficiently. This will become a useful disinfection system.

PMID- 18045414
TI  - Arsenic-resistant bacteria isolated from contaminated sediments of the Orbetello
      Lagoon, Italy, and their characterization.
AB  - AIMS: The aim of this study was to isolate arsenic-resistant bacteria from
      contaminated sediment of the Orbetello Lagoon, Italy, to characterize isolates
      for As(III), As(V), heavy metals resistance, and from the phylogenetic point of
      view. METHODS AND RESULTS: Enrichment cultures were carried out in the presence
      of 6.75 mmol l(-1) of As(III), allowing isolation of ten bacterial strains. Four
      isolates, ORAs1, ORAs2, ORAs5 and ORAs6, showed minimum inhibitory concentration
      values equal or superior to 16.68 mmol l(-1) and 133.47 mmol l(-1) in the
      presence of As(III) and As(V), respectively. Isolate ORAs2 showed values of 1.8
      mmol l(-1) in the presence of Cd(II) and 7.7 mmol l(-1) of Zn(II), and isolate
      ORAs1 pointed out a value of 8.0 mmol l(-1) in the presence of Cu(II). Analysis
      of 16S rRNA gene sequences revealed that they can be grouped in the three genera
      Aeromonas, Bacillus and Pseudomonas. Phylogenetic analysis of the four more
      arsenic-resistant strains was also performed. CONCLUSION: Isolates are highly
      resistant to both As(III) and As(V) and they could represent good candidates for
      bioremediation processes of native polluted sediments. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This study provides original results on levels of resistance to
      arsenic and to assigning genera of bacterial strains isolated from arsenic
      polluted sediments.

PMID- 18045415
TI  - Diagnosis of Xanthomonas axonopodis pv. citri, causal agent of citrus canker, in
      commercial fruits by isolation and PCR-based methods.
AB  - AIMS: To show the results of the detection of an EU quarantine organism,
      Xanthomonas axonopodis pv. citri (Xac), in citrus fruits imported from countries
      where this bacterium is present, using an integrated approach that includes
      isolation, pathogenicity assays and molecular techniques. METHODS AND RESULTS:
      Citrus fruits with canker-like symptoms, exported to Spain from South American
      countries were analysed by several methods. Bacterial isolation, three
      conventional polymerase chain reaction (PCR) protocols, and real-time PCR with
      SYBR Green or a TaqMan probe, were compared. Canker-like lesions were disrupted
      in PBS buffer, and the extract used for bacterial isolation and DNA extraction
      followed by PCR amplification. Canker lesions, identified by PCR, showed viable
      bacteria in eleven of fifteen fruit samples. In 16 out of 130 lesions analysed
      from these samples, Xac was isolated, and pathogenicity on grapefruit leaves
      confirmed. By real-time PCR, using SYBR green or a Taqman probe, Xac was detected
      in 58 and 80 lesions respectively. By conventional PCR the bacterium was detected
      in 39-52 lesions depending on the protocol employed. CONCLUSIONS: An integrated
      approach for reliable detection of Xac in lesions of fruit samples, employing
      several techniques and with real-time PCR using a TaqMan probe as the fastest and
      most sensitive screening method, has been established and validated and is
      proposed as a useful tool for the analysis of Xac on fresh fruits. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This work faces up to the real threat of the importation
      of citrus fruits that can harbour quarantine bacteria and will be useful in
      diagnostic laboratories for the analysis of commercial fresh fruits from
      countries where citrus canker is present.

PMID- 18045416
TI  - The glutamate decarboxylase acid resistance mechanism affects survival of
      Listeria monocytogenes LO28 in modified atmosphere-packaged foods.
AB  - AIMS: The contribution of the glutamate decarboxylase (GAD) acid resistance
      system to survival and growth of Listeria monocytogenes LO28 in modified
      atmosphere-packaged foods was examined. METHODS AND RESULTS: The survival and
      growth of the wild-type LO28 and four GAD deletion mutants (DeltagadA, DeltagadB,
      DeltagadC, DeltagadAB) in packaged foods (minced beef, lettuce, dry coleslaw mix)
      during storage at 4, 8 and 15 degrees C were studied. Survival and growth
      patterns varied with strain, product type, gas atmosphere and storage
      temperature. In minced beef, the wild-type LO28 survived better (P < 0.05) than
      the GAD mutant strains at 8 and 15 degrees C. In both packaged vegetables at all
      storage temperatures, the wild-type strain survived better (P < 0.05) than the
      double mutant DeltagadAB. The requirement for the individual gad genes varied
      depending on the packaged food. In the case of lettuce, gadA played the most
      important role, while the gadB and gadC genes played the greatest role in
      packaged coleslaw (at 15 degrees C). CONCLUSIONS: This work demonstrates that
      elements of the GAD system play significant roles in survival of L. monocytogenes
      LO28 during storage in modified atmosphere-packaged foods. SIGNIFICANCE AND
      IMPACT OF THE STUDY: A better understanding of how L. monocytogenes behaves in
      modified atmosphere-packaged foods, and how it responds to elevated carbon
      dioxide atmospheres.

PMID- 18045417
TI  - Grapevine yellows in Northern Italy: molecular identification of Flavescence
      doree phytoplasma strains and of Bois Noir phytoplasmas.
AB  - AIMS: Verify the presence and the molecular identity of phytoplasmas in Northern
      and Central Italy vineyards where yellows diseases are widespread. METHODS AND
      RESULTS: Phytoplasma presence and identity were determined by PCR/RFLP analyses
      on 16S ribosomal gene testing 1424 symptomatic samples. The 65% of samples
      resulted phytoplasma infected; in particular 256 samples were found positive to
      phytoplasmas belonging to group 16SrV (mainly Flavescence doree associated), and
      the remaining 37% was infected by phytoplasmas belonging to ribosomal subgroup
      16SrXII-A (Stolbur or Bois Noir associated). 16SrV ribosomal group representative
      strains were further typed for variability in SecY and rpS3 genes. The results
      showed the presence of phytoplasmas belonging to 16SrV-C, 16SrV-D and to a lesser
      extent, 16SrV-A subgroup. CONCLUSIONS: Possible relationships between genetic
      polymorphisms of phytoplasma strains belonging to subgroup 16SrV-C and their
      geographic distribution and/or epidemic situations were detected. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Bois Noir and Flavescence doree phytoplasmas are present
      in significant percentages in the areas under investigation. Molecular tools
      allowed to identify phytoplasma-infected plants and the genes employed as
      polymorphism markers resulted useful in distinguishing and monitoring the
      spreading of the diseases associated with diverse phytoplasmas belonging to 16SrV
      subgroup in vineyards.

PMID- 18045418
TI  - Isolation, purification and characterization of an antifungal molecule produced
      by Bacillus licheniformis BC98, and its effect on phytopathogen Magnaporthe
      grisea.
AB  - AIMS: Isolation of bacterial antagonist for use in the biological control of
      phytopathogenic fungi like rice blast fungus, Magnaporthe grisea, and to further
      purify and characterize the antifungal molecule produced by the antagonist.
      METHODS AND RESULTS: Bacterial antagonist exhibiting highest antifungal activity
      against the rice blast fungus M. grisea was isolated from soil and identified as
      Bacillus licheniformis BC98. Besides M. grisea, the isolate also inhibited the
      growth of other phytopathogens such as Curvularia lunata and Rhizoctonia
      bataticola. Biologically active fractions were isolated from the culture filtrate
      and further fractionated by reverse-phase high-performance liquid chromatography
      (HPLC) enabling detailed structural characterization of a component of molecular
      mass 1035 Da. The active peptide was identified as surfactin after 500 MHz (1)H
      NMR analysis. Microscopic analysis of the effect of the antagonist on M. grisea
      revealed bulbous hyphae showing patchy and vacuolated cytoplasm when observed
      under the electron microscope. CONCLUSIONS: The antagonistic lipopeptide secreted
      by B. licheniformis BC98 and identified as surfactin, induced morphological
      changes in M. grisea, inhibiting its further growth, and thus exhibiting
      fungicidal activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The antagonist
      inhibits germination of M. grisea, a potent rice phytopathogen, and therefore
      appears to be a potential candidate for control of rice blast disease.

PMID- 18045419
TI  - The effect of NADP-dependent malic enzyme expression and anaerobic C4 metabolism
      in Escherichia coli compared with other anaplerotic enzymes.
AB  - AIMS: To understand the modification of C4-metabolism under anaerobic glycolysis
      condition by overexpressing anaplerotic enzymes, which mediating carboxylation of
      C3 into C4 metabolites, in Escherichia coli. METHODS AND RESULTS: Anaplerotic
      NADP-dependent malic enzyme (MaeB), as well as the other anaplerotic enzymes,
      including phosphoenolpyruvate carboxylase (Ppc), phosphoenolpyruvate
      carboxykinase (Pck) and NAD-dependent malic enzyme (MaeA), were artificially
      expressed and their C4 metabolism was compared in E. coli. Increasing MaeB
      expression enhanced the production of C4 metabolites by 2.4 times compared to the
      wild-type strain in anaerobic glucose medium with bicarbonate supplementation. In
      MaeB expression, C4 metabolism by supplementing 10 g l(-1) of NaHCO(3) was three
      times than that by no supplementation, which showed the greatest response to
      increased CO(2) availability among the tested anaplerotic enzyme expressions.
      CONCLUSIONS: The higher C4 metabolism was achieved in E. coli expressing
      increased levels of the NADPH-dependent MaeB. The greatest increase in the C4
      metabolite ratio compared to the other tested enzymes were also found in E. coli
      with enhanced MaeB expression as CO(2) availability increased. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The higher C4 metabolites and related biomolecule
      productions can be accomplished by MaeB overexpression in metabolically
      engineered E. coli.

PMID- 18045420
TI  - Global gene expression of Trichophyton rubrum in response to PH11B, a novel fatty
      acid synthase inhibitor.
AB  - AIMS: To determine the transcriptional responses of Trichophyton rubrum to the
      artificial substance, PH11B. METHODS AND RESULTS: The broth microdilution assay
      for antifungal susceptibility testing of dermatophytes was used to measure the
      minimum inhibitory concentration (MIC) of PH11B. cDNA microarray technology and
      real-time RT-PCR were used to study the transcriptional responses of T. rubrum to
      PH11B. The MIC determined was 16 microg ml(-1). The analysis of microarray data
      revealed that 787 genes were affected. Transcript levels from 476 genes increased
      at least two times, while 311 gene transcript levels decreased at least two
      times. CONCLUSIONS: PH11B has strong antifungal activity and the transcriptional
      response of T. rubrum to PH11B was determined. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This microarray data set provides an analysis of gene expression of T.
      rubrum under PH11B treatment. The data provide an insight into the various
      metabolic processes altered or activated by PH11B. This study provided an insight
      into the action mode of the PH11B on T. rubrum.

PMID- 18045421
TI  - Characterization of antimicrobial resistant Escherichia coli isolated from
      processed bison carcasses.
AB  - AIM: To determine the phenotypic and genotypic antimicrobial susceptibility
      profiles of Escherichia coli from bison carcasses. METHODS AND MATERIALS: The
      antimicrobial resistance of 138 E. coli isolates recovered from processed bison
      carcasses was determined by using the National Antimicrobial Resistance
      Monitoring System panels, polymerase chain reaction assays, plasmid analysis and
      conjugation studies. RESULTS: Resistance to 14 of the 16 antimicrobials was
      observed. Twenty-three (16.7%) isolates displayed resistance to at least one
      antimicrobial agent. The most prevalent resistances were to tetracycline (13.0%),
      sulfamethoxazole (7.9%) and streptomycin (5.8%). No resistance was observed to
      amikacin and ciprofloxacin. Further analysis of 23 antimicrobial-resistant E.
      coli isolates showed the presence of resistance genes corresponding to their
      phenotypic profiles. Results of conjugation studies carried out showed most
      isolates tested were able to transfer their resistance to recipients. CONCLUSION:
      This study indicated that multidrug-resistant E. coli isolates are present in
      bison. However, the resistance rate is lower than that reported in other meat
      species. SIGNIFICANCE AND IMPACT OF THE STUDY: The beneficial effects of
      antimicrobial-free feeding practice in bison may be promoting a reduction in the
      prevalence of antimicrobial resistance in commensal flora of bison.

PMID- 18045422
TI  - The in vitro effect of gossypol and its interaction with salts on conidial
      germination and viability of Fusarium oxysporum sp. vasinfectum isolates.
AB  - AIMS: To assess the effect of different concentrations of gossypol (0, 2, 4, 10
      and 20 mg l(-1)) in combination with NaCl and Na(2)SO(4) (20 mS cm(-1)) on the
      conidial germination and viability of Fusarium oxysporum f.sp. vasinfectum (Fov).
      METHODS AND RESULTS: A multinomial logistic model was developed to estimate the
      germination probability of Fov. The inhibitory effect was markedly evident at the
      two highest concentrations of gossypol; it varied among the isolates tested and
      with time, and it was attenuated by the presence of sodium salts. The inhibition
      was temporary as the germination probability increased after 8 h. Fluorescent
      staining revealed that gossypol either killed the conidia or retarded the
      elongation of the germ tubes. CONCLUSION: Fov showed the ability to overcome
      gossypol inhibition over time, and the inhibitory effect is reduced under saline
      conditions. Differential responses among Fov isolates to the presence of gossypol
      suggest that gossypol tolerance is genetically determined in the pathogen.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that selecting for high
      plant gossypol cultivars would have minimal effect on the overall Fov resistance
      of cotton. A new statistical model was developed to explore the statistical
      significance of plant-pathogen interactions.

PMID- 18045423
TI  - Potential of AbiS as defence mechanism determined by conductivity measurement.
AB  - AIM: To compare pH and conductivity used in the determination of growth in
      reconstituted skim milk (RSM), to determine whether the presence of one or two
      plasmids in Lactococcus lactis had any influence on growth, and whether AbiS
      improved bacteriophages resistance of L. lactis. METHODS AND RESULTS:
      Conductivity and pH were used to determine growth in RSM. A small increase in the
      generation time was found with increasing number of plasmids, while their size
      was unimportant. The introduction of a plasmid-encoding AbiS did only enhance the
      level of phage resistance significant when other plasmids encoding either AbiS1
      or the restriction modification system LlaBIII was present. CONCLUSIONS: The
      earliest detection of growth was observed by measuring pH, rather than
      conductance. The plasmid-encoded AbiS system has a potential to be used as a
      phage resistance mechanisms in L. lactis during milk fermentations, especially
      when combined with other anti-phage mechanisms. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study widened the knowledge about the influence of plasmid
      introduction on the growth rate of L. lactis, which is important for the
      construction of new strains. The level of protection against 936 groups of phages
      was only significant when the mechanism was present together with the RM system
      LlaBIII.

PMID- 18045424
TI  - Prebiotics enhance survival and prolong the retention period of specific
      probiotic inocula in an in vivo murine model.
AB  - AIM: To identify novel prebiotics that could be used to maintain persistence of
      three representative probiotic strains in vivo. METHODS AND RESULTS: Test mice
      were treated with prebiotics soybean oligosaccharide (SOS), fructooligosaccharide
      (FOS) or inulin, followed by probiotics Lactobacillus acidophilus LAFTI L10
      (L10), Bifidobacterium lactis LAFTI B94 (B94) or Lactobacillus casei L26 LAFTI
      (L26). Faecal samples were then collected and analysed using selective medium and
      PCR analysis to determine the presence of the probiotic strains. In contrast to
      the control groups, in mice fed prebiotics, the survival and retention time of
      the test probiotics was increased extensively. SOS and FOS prolonged the
      retention period of L10 from 24 to 30 h. Of the three prebiotics, FOS gave the
      best result with B94, prolonging the retention period from 3 to > or =10 days. Of
      the three prebiotics, inulin gave the best result for L26, prolonging the
      retention period from 2 to > or =6 days. CONCLUSIONS: The prebiotics SOS, FOS and
      inulin significantly enhance survival and prolong the retention period of L10,
      B94 and L26 in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results
      demonstrate the potential use of FOS, inulin and SOS as prebiotics in conjunction
      with the probiotic strains L10, B94 and L26 for new synbiotic products.

PMID- 18045425
TI  - Prevalence and molecular characterization of Escherichia coli O157:H7 on Irish
      lamb carcasses, fleece and in faeces samples.
AB  - AIMS: To determine the prevalence, seasonal variation and virulence
      characteristics of Escherichia coli O157:H7 in lambs presented for slaughter in
      Ireland. METHODS AND RESULTS: Over a 13-month period, pre- and postchill carcass
      swabs, faeces and fleece samples from 1600 lambs were examined for the presence
      of E. coli O157:H7. Escherichia coli O157:H7 was isolated from 5.75% (23/400) of
      fleece samples, 1.5% (6/400) of pre- and 1% (4/400) of postchill carcass swabs
      but was not isolated in faeces (0/400). The present study detected no evidence of
      seasonal variation. Polymerase chain reaction analysis showed that both the vt1
      and vt2 genes associated with clinical illness were carried by five of the E.
      coli O157:H7 isolates, while 24 of the remaining isolates carried the vt2 gene
      only. Phage typing detected four different subtypes: PT 32 (48.48%), PT 8
      (12.12%), PT 31 (12.12%) and PT 21/28 (12.12%). CONCLUSIONS: Escherichia coli
      O157:H7 is present in lambs at slaughter in Irish abattoirs and the virulence
      profiles of these isolates reveals that they are potentially harmful to humans.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The present study provides crucial
      information indicating that sheep may be a significant contributing source to
      human E. coli O157:H7 infection.

PMID- 18045426
TI  - Volume recovery, surface properties and membrane integrity of Lactobacillus
      delbrueckii subsp. bulgaricus dehydrated in the presence of trehalose or sucrose.
AB  - AIMS: Although the practical importance of adding sugars before drying is well
      known, the mechanism of protection of bacteria by sugars is not clear. The
      response of the dehydrated micro-organisms to rehydration is analysed in terms of
      structural and functional changes, and correlated with their potentiality to grow
      in rich media. These aspects are related with the membrane integrity and the
      metabolic state of the rehydrated bacteria, measured by means of surface
      properties and permeability. To attain this objective, Lactobacillus delbrueckii
      subsp. bulgaricus was dehydrated in the presence and in the absence of sucrose
      and trehalose. The bacterial response upon rehydration was investigated by
      determining: (i) the lag time of the bacterial growing in rich media, (ii) the
      restoration of the surface properties and the cellular volume and (iii) the
      membrane integrity. METHODS AND RESULTS: Lactobacillus delbrueckii subsp.
      bulgaricus was grown in MRS at 37 degrees C overnight [De Man et al. (1960)J Appl
      Bacteriol 23, 130] and then dehydrated for 10, 20 and 30 min at 70 degrees C in a
      vacuum centrifuge. The lag time of micro-organisms was determined by optical
      density changes after rehydration. The surface properties were determined by
      measuring the zeta potential of the bacteria suspended in aqueous solution. The
      cellular volume recovery was measured, after stabilization in saline solution, by
      light scattering and by the haematocrit method [Alemohammad and Knowles (1974)J
      Gen Microbiol 82, 125]. Finally, the membrane integrity has been determined by
      using specific fluorescent probes [SYTO 9 and propidium iodide, (PI)] that bind
      differentially depending on the integrity of the bacterial membrane. The lag time
      of Lact. delbrueckii subsp bulgaricus, dehydrated by heat in the presence of
      sucrose or trehalose and after that rehydrated, was significantly shortened, when
      compared with that obtained for bacteria dried in the absence of sugars. In these
      conditions, trehalose and sucrose maintained the zeta potential and the cell
      volume close to the control (nondried) cells. However, the membrane integrity,
      measured with fluorescent probes, was maintained only when cells were dehydrated
      for 10 min in the presence of sugars. For larger times of dehydration, the
      membrane integrity was not preserved, even in the presence of sugars.
      CONCLUSIONS: When the micro-organisms are dehydrated in the absence of
      protectants, the membrane damage occurs with a decrease in the absolute value of
      the zeta potential and a decrease in the cellular volume recovered after
      rehydration. In contrast, when the zeta potential and the cellular volume are
      restored after rehydration to that corresponding to nondried cells, the micro
      organisms are able to recover and grow with a reduced lag time. This can only be
      achieved when the dehydration is carried out in the presence of sugars. At short
      dehydration times, the response is associated with the preservation of the
      membrane integrity. However, for longer times of dehydration the zeta potential
      and volume recovery occurs in the presence of sugars in spite of a severe damage
      at membrane level. In this condition, cells are also recovered. In conclusion, to
      predict the ability of growing after dehydration, other bacterial structural
      parameters besides membrane integrity, such as zeta potential and cellular
      volume, should be taken into account. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      correlation of the lag time with the surface and permeability properties is of
      practical importance because the correlation of these two parameters with cell
      viability, allow to determine the potential bacterial capacity to grow in a rich
      medium after the preservation procedure, without necessity of performing a
      kinetic curve of growth, which is certainly time-consuming.

PMID- 18045427
TI  - Occurrence and levels of indicators and selected pathogens in different sludges
      and biosolids.
AB  - AIMS: Determine the occurrence and levels of pathogens and indicators in raw and
      treated sludges and compare their persistence after two different treatments.
      METHODS AND RESULTS: Helminth ova, Cryptosporidium spp., Salmonella spp.,
      enteroviruses, and bacterial and viral indicators were determined in raw sludges
      and biosolids produced after mesophilic and thermophilic treatments. Except
      Salmonella, all of the parameters were quantified. Helminth ova were found at
      very low concentrations even in raw sludges. Viable Cryptosporidium oocysts were
      still present in most samples of treated sludges. Faecal coliforms, spores of
      sulphite-reducing clostridia (SSRC), and somatic coliphages were the only
      indicators with values above their detection limits in most of the samples.
      CONCLUSIONS: Pathogens were still detected in some treated sludge samples. SSRC
      were the most resistant micro-organisms to treatments and hence may be an
      indicator for the reduction of protozoan oocysts. Somatic coliphages constitute
      an alternative as viral indicators due to their detection in sludges before and
      after treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of the persistence
      of some pathogens after sludge treatments, additional indicators are needed. SSRC
      and somatic coliphages are good candidates. Easy and inexpensive methods for the
      determination of these indicators are feasible both in industrialized and
      developing countries.

PMID- 18045428
TI  - Multilocus genetic analysis of Cryptosporidium in naturally contaminated bivalve
      molluscs.
AB  - AIMS: To evaluate the application of discriminatory multilocus PCR procedures for
      the characterization of Cryptosporidium in samples of naturally contaminated
      bivalve molluscan shellfish. METHODS AND RESULTS: Nucleic acid was extracted from
      22 shellfish previously identified as contaminated with Cryptosporidium spp. and
      subjected to PCR-based analysis for two independent fragments of the
      Cryptosporidium oocyst wall protein (COWP) gene, three microsatellite markers (ML
      1, GP 15 and MS 5) and an extra-chromosomal small double-stranded RNA (dsRNA).
      Overall, at least one COWP gene fragment was amplified from all 22 samples, 21
      amplified the dsRNA and 14 at least one of the three microsatellite loci. More
      than one dsRNA or microsatellite allele was detected in 50% of samples. The
      majority of samples were contaminated with Cryptosporidium parvum types
      circulating in both humans and livestock. A novel dsRNA element was identified in
      one sample, which did not amplify any of the three microsatellite loci
      investigated. CONCLUSIONS: Multilocus analysis of Cryptosporidium can be applied
      to DNA extracted from naturally contaminated shellfish. SIGNIFICANCE AND IMPACT
      OF STUDY: This multilocus genetic analysis highlights that filter feeder molluscs
      are a potential source of cryptosporidial oocysts, which may be infectious to
      humans.

PMID- 18045429
TI  - Use of selected indigenous Saccharomyces cerevisiae strains for the production of
      the traditional cachaca in Brazil.
AB  - AIMS: To test indigenous Saccharomyces cerevisiae as starters to produce cachaca
      in large-scale in a traditional distillery, establishing the period in which,
      each strain predominates in the vats, chemical composition and sensory attributes
      of the beverage, and to compare these data with vats prepared by spontaneous
      fermentation. METHODS AND RESULTS: Strains were evaluated for kinetic
      fermentation parameters, permanence in vats, volatile compound production, and
      sensory attributes for the cachacas produced. In general the vats in which
      starter strains were used, no difference in restriction mitochondrial DNA (mtDNA)
      profiles of isolates was observed. In the vats in which spontaneous fermentation
      occurred, different mtDNA restriction profiles were observed. Most of the non
      Saccharomyces species isolated could be regarded as contaminants of fermentation.
      All cachacas produced, despite being recently distilled and with differences in
      their chemical composition, were well accepted by the judges. CONCLUSIONS: It was
      possible to detect the differences in the fermentation capacities of S.
      cerevisiae strains, in their relative abundances at different time periods, and
      in the chemical compositions and sensory attributes of the resulting beverages.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The indigenous strains utilized to prepare
      cachaca have shown potential to be used as starters of this traditional
      fermentation process.

PMID- 18045430
TI  - Environment and virulence factors of Vibrio cholerae strains isolated in
      Argentina.
AB  - AIMS: To determine the presence of Vibrio cholerae in different areas of
      Argentina in three sample types, to determine the composition of planktonic
      communities in areas at which this pathogen was detected and to characterize the
      virulence properties and antimicrobial resistance of the recovered environmental
      isolates. METHODS AND RESULTS: Water and plankton samples were collected in
      marine, brackish and freshwater environments. Vibrio cholerae non-O1, non-O139
      was isolated in 36.1% of the samples analysed. The micro-organism was detected in
      freshwater but not in marine or brackish samples. No relationship was found
      between isolation of V. cholerae and presence of any species of plankton. All the
      isolates presented very similar virulence profiles by PCR, lacking ctxA and tcpA
      El Tor and containing hlyA (98.7%), rtxA (99.0%), toxR (98.7%) and stn-sto
      (1.9%). Resistance to ampicillin was found in both Tucuman (21%) and Buenos Aires
      isolates (45%). CONCLUSIONS: We identified two geographic areas in Argentina
      where V. cholerae was present: freshwaters of the rivers from Tucuman and the Rio
      de la Plata. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of V.
      cholerae strains in the environment, carrying both virulence factors and
      resistance to antimicrobial agents, highlight the need for a continuous and
      active surveillance of this pathogen.

PMID- 18045431
TI  - Shiga-toxigenic Escherichia coli O157 and non-Shiga-toxigenic E. coli O157
      respond differently to culture and isolation from naturally contaminated bovine
      faeces.
AB  - AIM: To quantify the effect of enrichment, immunomagnetic separation (IMS), and
      selective plating procedures on isolation of Shiga-toxigenic Escherichia coli
      O157 (STEC O157) and non-Shiga-toxigenic Escherichia coli O157 (non-STEC O157)
      from naturally contaminated bovine faeces. METHODS AND RESULTS: Two broth
      enrichment times, two IMS strategies, and two selective plating media were
      evaluated. STEC O157 and non-STEC O157 strains were often isolated from the same
      faecal specimen and responded differently to the isolation protocols. A large
      volume IMS system was more sensitive than a conventional small-volume IMS method,
      but was also more expensive. STEC O157 was more frequently isolated from 6 h
      enriched broth and ChromAgar plates containing 0.63 mg l(-1) potassium tellurite
      (TCA). Non-STEC O157 was more frequently isolated from un-enriched broth and
      ChromAgar plates without tellurite (CA). CONCLUSIONS: The combination of 6-h
      enrichment in Gram-negative broth containing vancomycin, cefixime and cefsuludin,
      large volume IMS and selective plating on TCA maximized STEC O157 recovery from
      naturally contaminated cattle faecal specimens. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The pairing of proper enrichment with a specific plating procedure is key
      for STEC O157 recovery from naturally contaminated bovine faeces. Incorporating
      tellurite into an E. coli O157 detection strategy may select for the subset of E.
      coli O157 that contains the Shiga-toxin genes.

PMID- 18045432
TI  - Integration of the group c phage JCL1032 of Lactobacillus delbrueckii subsp.
      lactis and complex phage resistance of the host.
AB  - AIMS: Sequences related to Lactobacillus delbrueckii phage JCL1032 genome
      integration, the maintenance of lysogeny and putative immunity genes were
      characterized. Phenotypic changes of the JCL1032 lysogens were investigated.
      METHODS AND RESULTS: Integration of JCL1032 DNA into the host genome and the
      location of phage and bacterial attachment sites were studied by standard
      molecular methods. The frequency of lysogenization was 10(-7), and stable
      lysogeny was an even rarer phenomenon. JCL1032 integrates its genome into two
      distinct host genes of unknown functions. According to EOP (efficiency of
      plating) and adsorption tests JCL1032 lysogens showed resistance against several
      virulent and temperate Lactobacillus phages at different steps of phage
      infection. CONCLUSIONS: Temperate JCL1032 integrates its genome into bacterial
      DNA with exceptionally low frequency. JCL1032 lysogens express a complex phage
      resistance against several Lact. delbrueckii phages. An antagonistic arms race
      between the temperate phage and its host is proposed. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This is the first time that the genome integration of a group c Lact.
      delbrueckii phage has been described. The characterized lysogens could facilitate
      studies on Lact. delbrueckii phage receptors and phage resistance mechanisms. The
      genetic information gained from this study benefits the development of
      integration vectors and phage resistant starters.

PMID- 18045433
TI  - Cloning and phylogenetic analysis of the chitinase gene from the facultative
      pathogen Paecilomyces lilacinus.
AB  - AIMS: To PCR-amplify the full-length genomic-encoding sequence for one chitinase
      from the facultative fungal pathogen Paecilomyces lilacinus, analyse the DNA and
      deduced amino acid sequences and compare the amino acid sequence with chitinases
      reported from mycopathogens, entomopathogens and nematopathogens. METHODS AND
      RESULTS: The encoding gene (designated as PLC) was isolated using the degenerate
      PCR primers and the DNA-Walking method. The gene is 1458 bp in length and
      contains three putative introns. A number of sequence motifs that might play a
      role in its regulation and function had also been found. Alignment of the
      translation product (designated as Plc, molecular mass of 45.783 kDa and pI of
      5.65) with homologous sequences from other species showed that Plc belongs to
      Class V chitinase within the glycosyl hydrolase family 18. The phylogenetic and
      molecular evolutionary analysis using mega (Molecular Evolutionary Genetics
      Analysis) indicated that these chitinases from mycopathogens, entomopathogens and
      nematopathogens, the majority of which belong to glycosyl hydrolase family 18,
      were clustered into two well-supported subgroups corresponding to ascomycetes
      fungal and nonfungal chitinases (bacteria, baculoviruses). CONCLUSIONS: Our study
      showed that chitinases from mycoparasitic, entomopathogenic and nematophagous
      fungi are closely related to each other and reaffirmed the hypothesis that
      baculovirus chitinase is most likely to be of a bacterial origin - acquired by
      gene transfer. Bacterial and baculoviral chitinases in our study are potential
      pathogenicity factors; however, we still cannot ascribe any specific function to
      those chitinases from the fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: To our
      knowledge, this is the first report describing the chitinase gene and its
      translation product from Paecilomyces lilacinus, which constitutes the largest
      number of formulated biological nematicides reported so far, this is also the
      first study to analyse and resolve the phylogenetic and molecular evolutionary
      relationships among the chitinases produced by mycopathogens, entomopathogens and
      nematopathogens.

PMID- 18045434
TI  - Characterization of dominant cultivable lactobacilli and their antibiotic
      resistance profiles from faecal samples of weaning piglets.
AB  - AIMS: To examine the lactic acid bacteria flora of weaning piglets, to define the
      distribution of different lactobacilli species in piglet faecal samples, and to
      determine the susceptibility phenotype to 11 antibiotic of different families.
      METHODS AND RESULTS: The faecal samples were taken from piglets with good herd
      status at 11 and 28 days after weaning. The Lactobacillus isolates (n = 129) from
      78 animals housed in pairs in 39 pens were preliminarily identified by their
      morphology and biochemical characteristics. Partial 16S ribosomal DNA (16S rDNA)
      was used to identify the isolates to the species level, and RAPD (randomly
      amplified polymorphism DNA) profiles to differentiate Lactobacillus isolates to
      the strain level. Based on these studies, 67 strains were selected for antibiotic
      resistant tests. The most numerous Lactobacillus species found in the piglets was
      Lactobacillus reuteri (n = 43). Other lactobacilli were L. salivarius (n = 15),
      L. agilis (n = 4), L. johnsonii (n = 2), L. vaginalis (n = 1), L. mucosae (n = 1)
      and L. gallinarum (n = 1). All the strains were susceptible to chloramphenicol,
      ampicillin and gentamicin. Two L. salivarius isolates and two L. reuteri isolates
      were found to be multiresistant. CONCLUSIONS: This study indicates that the
      faecal Lactobacillus flora in piglets consists mainly of L. reuteri, L.
      salivarius and L. acidophilus group lactobacilli, and the distribution of
      lactobacilli is similar between individuals of the same age and with the same
      diet. Most of the Lactobacillus isolates tested were sensitive to the antibiotics
      used in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: Valuable information on
      Lactobacillus species distribution and their antibiotic resistance profiles in
      piglets is obtained.

PMID- 18045435
TI  - Inhibition of biofilms associated with dentures and toothbrushes by tetrasodium
      EDTA.
AB  - AIMS: We examined the efficacy of tetrasodium EDTA in eradicating biofilms
      derived from salivary inocula or pure cultures of Candida albicans on discs of
      polymethyl methacrylate (PMMA) denture base or on toothbrushes that had been used
      normally for 4-8 weeks. Its efficiency in virus neutralization was also
      determined. METHODS AND RESULTS: Overnight (16 h) treatment with 4% (w/v)
      tetrasodium EDTA solution reduced salivary and C. albicans biofilm viable counts
      by > or =99%. Biofilm removal was confirmed using confocal laser scanning
      microscopy. Presence/absence of sucrose during biofilm formation had no effect on
      killing efficacy. Prolonged treatment of PMMA with tetrasodium EDTA did not
      influence subsequent formation of C. albicans biofilms or affect surface
      roughness of the PMMA, but it reduced subsequent biofilm formation from a
      salivary inoculum. Infectivities of herpes simplex virus and polio virus
      suspensions were reduced by >99.99% by treatment for 1 and 2 h, respectively.
      CONCLUSIONS: Tetrasodium EDTA solution efficiently disinfected toothbrushes and
      PMMA discs, with the detachment of biofilms, and rapidly neutralized both
      nonenveloped and enveloped viruses. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Dentures and toothbrushes become contaminated by bacterial biofilms and by
      viruses. There is a need for disinfection methods that are rapidly effective,
      cost-effective, nontoxic and easily implemented. These studies indicate that
      tetrasodium EDTA solution has disinfection applications in the oral care field.

PMID- 18045436
TI  - The influence of L-ascorbic acid on the antibacterial-toxic activity of
      aflatoxins on adsorbent layer.
AB  - AIMS: To substantiate the role of formaldehyde (HCHO) and its reaction products
      in the mechanism of the antibacterial-toxic effect of aflatoxins B1 (AFB1), B2,
      G1 and G2. MATERIALS AND RESULTS: Toxins were separated by overpressured layer
      chromatography, which was followed by biological evaluation directly on the
      adsorbent layer (BioArena system with Pseudomonas savastanoi pv. phaseolicola
      indicator bacteria). HCHO formed in this system was eliminated with exogenously
      added capturer molecule dimedone and L-ascorbic acid (AA) and measured as the
      adduct of dimedone and HCHO. The amount of HCHO was higher in the toxin
      containing spots, particularly in the most toxic AFB1 spot, compared to a
      toxinless background. 0.1 mg ml(-1)AA augmented, 0.2 mg ml(-1) dimedone or 0.5
      and 1 mg ml(-1) AA reduced the antibacterial effect of all four aflatoxins.
      CONCLUSION: The antibacterial-toxic effect of aflatoxins may be mediated by HCHO
      (and/or its reaction products) generated from bound HCHO forms in the bacterial
      cells. Basis of antibacterial-toxic activity of the four aflatoxins appears the
      same. SIGNIFICANCE AND IMPACT OF THE STUDY: Involvement of HCHO as a key molecule
      in the effect of aflatoxins indicates a totally new mechanism of action of these
      dangerous molecules. The BioArena system is useful to dissect the mode of action
      of antimicrobial compounds from different biological matrices.

PMID- 18045437
TI  - Isolation of a novel strain of Aeromonas media producing high levels of DOPA
      melanin and assessment of the photoprotective role of the melanin in
      bioinsecticide applications.
AB  - AIMS: To isolate a bacterium that produces high yield of melanin and to examine
      the effect of this bacterial pigment on the efficacy of a bioinsecticide. METHODS
      AND RESULTS: A novel melanin-producing bacterium, designated as strain WS, was
      isolated from the East Lake, Wuhan, China. Taxonomic studies of this strain
      indicate that it belongs to Aeromonas media. Physicochemical analysis of the
      pigment produced by strain WS (melanin WS) suggests that it is the authentic 3,4
      dihydroxyphenylalanine (DOPA)-melanin. This melanin and that produced by
      Pseudomonas maltophilia P28 (melanin P28) share many biophysical properties, but
      the yield of the melanin WS is significantly higher than that of the melanin P28.
      In addition, the melanin WS appears to be more effective in the protection of a
      bioinsecticide against ultraviolet (UV) or solar radiation. At the concentration
      of 10 ppm, the melanin P28 exhibited no photoprotective effect on the
      bioinsecticide against UV radiation; in contrast, 5 ppm of melanin WS displayed
      an obvious protective effect. Similarly, the melanin WS displayed more protective
      effect on the bioinsecticide against solar radiation than the melanin P28 did
      over a 4-day period, with the effect being more dramatic for the last 2 days.
      CONCLUSIONS: We have isolated a novel bacterial strain of A. media that produces
      high levels of melanin. The melanin produced by this strain offers effective
      photoprotection of a commercial bioinsecticide BTI against UV and solar
      radiation. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study suggests that the
      melanin produced by our newly isolated A. media strain has the potential to be
      used as a general photoprotective agent for bioinsecticides.

PMID- 18045438
TI  - Potential microbial risk factors related to soil amendments and irrigation water
      of potato crops.
AB  - AIMS: This study assesses the potential microbial risk factors related to the use
      of soil amendments and irrigation water on potato crops, cultivated in one
      traditional and two intensive farms during two harvest seasons. METHODS AND
      RESULTS: The natural microbiota and potentially pathogenic micro-organisms were
      evaluated in the soil amendment, irrigation water, soil and produce. Uncomposted
      amendments and residual and creek water samples showed the highest microbial
      counts. The microbial load of potatoes harvested in spring was similar among the
      tested farms despite the diverse microbial levels of Listeria spp. and faecal
      coliforms in the potential risk sources. However, differences in total coliform
      load of potato were found between farms cultivated in the autumn.
      Immunochromatographic rapid tests and the BAM's reference method (Bacteriological
      Analytical Manual; AOAC International) were used to detect Escherichia coli
      O157:H7 from the potential risk sources and produce. Confirmation of the positive
      results by polymerase chain reaction procedures showed that the
      immunochromatographic assay was not reliable as it led to false-positive results.
      CONCLUSIONS: The potentially pathogenic micro-organisms of soil amendment,
      irrigation water and soil samples changed with the harvest seasons and the use of
      different agricultural practices. However, the microbial load of the produce was
      not always influenced by these risk sources. Improvements in environmental sample
      preparation are needed to avoid interferences in the use of immunochromatographic
      rapid tests. SIGNIFICANCE AND IMPACT OF THE STUDY: The potential microbial risk
      sources of fresh produce should be regularly controlled using reliable detection
      methods to guarantee their microbial safety.

PMID- 18045439
TI  - Diversity and antimicrobial susceptibility of oxytetracycline-resistant isolates
      of Stenotrophomonas sp. and Serratia sp. associated with Costa Rican crops.
AB  - AIMS: To ameliorate the identification, evaluate the diversity, and determine the
      antimicrobial sensitivity of 19 oxytetracycline-resistant isolates of
      Stenotrophomonas sp. and Serratia sp. associated with Costa Rican crops. METHODS
      AND RESULTS: Phenotypical, chemotaxonomical, and molecular data allocated most
      isolates to the species Sten. maltophilia and Ser. marcescens. The API profiles,
      antimicrobial resistance patterns (ATB system), and BOX-polymerase chain reaction
      (PCR) genomic fingerprints of isolates of Stenotrophomonas sp. exhibited a higher
      degree of heterogeneity than those obtained for the isolates of Serratia sp. The
      former group of bacteria exhibited multiresistance to antimicrobials. In
      contrast, isolates of Serratia sp. were sensitive to the majority of the drugs
      tested. Changes in the results of the antibiograms throughout incubation, which
      indicate an induction of tolerance, were observed for isolates of both the
      species. Minimum inhibitory concentration of oxytetracycline, determined using E
      test stripes, were rather elevated. CONCLUSIONS: The occurrence of two species of
      opportunistic pathogens in crop-associated materials poses a risk to consumers in
      the community. SIGNIFICANCE AND IMPACT OF THE STUDY: The phenotypic and genotypic
      data presented could support epidemiologist and physicians dealing with
      infections caused by environmental strains of these taxa.

PMID- 18045440
TI  - Development of a novel triplex PCR assay for the detection and differentiation of
      thermophilic species of Campylobacter using 16S-23S rDNA internal transcribed
      spacer (ITS) region.
AB  - AIM: Campylobacter species are significantly implicated in human gastrointestinal
      infections. Of 20 species of Campylobacter, C. jejuni, C. coli and C. lari have
      been considered as the most important causative agents of human infections. In
      order to better understand the occurrence and epidemiology of these thermophilic
      Campylobacter species, an improved and rapid detection method is warranted. A
      novel triplex polymerase chain reaction (PCR) assay was developed based on the
      variable 16S-23S rDNA internal transcribed spacer (ITS) region to identify and
      discriminate between these species in water samples. METHODS AND RESULTS:
      Campylobacter species-specific primers for C. jejuni, C. coli and C. lari derived
      from highly variable sequences in the ITS region were used. Specificity of the
      newly designed primers and PCR conditions were verified using other species of
      Campylobacter as well as 31 different negative control species. The assay was
      further validated with 97 Campylobacter cultures from water samples. CONCLUSIONS:
      The assay was found to be simple, easy to perform, and had a high sensitivity,
      specificity and reproducibility. It enabled simultaneous detection and
      differentiation of multiple Campylobacter species in water samples. SIGNIFICANCE
      AND IMPACT OF STUDY: Use of the newly developed PCR assay, coupled with a
      previously developed rapid DNA template preparation step, will enable improved
      detection capabilities for Campylobacter species in environmental matrices.

PMID- 18045441
TI  - Antagonistic effects of the endophytic fungus Meira geulakonigii on the citrus
      rust mite Phyllocoptruta oleivora.
AB  - AIMS: The fungus Meira geulakonigii has been shown to reduce populations of
      citrus rust mite (CRM; Phyllocoptruta oleivora) on citrus leaves and fruits, in
      both the field and laboratory. However, attempts to isolate the fungus from
      leaves and fruits have been unsuccessful. The aims of this study were therefore
      to determine whether M. geulakonigii is a citrus endophyte, and to assess
      possible mechanisms involved in its mite-antagonist activity. METHODS AND
      RESULTS: A quantitative real-time PCR and regular PCR approaches were developed
      to detect M. geulakonigii in both the field and laboratory. The fungus was
      detected throughout. Different methods revealed that M. geulakonigii is an
      endophyte, which colonizes both the peel of grapefruits. Applications of conidia
      protected the grapefruits against CRM, and fungal secretions extracted from
      growth media caused 100% CRM mortality. CONCLUSIONS: Meira geulakonigii is a
      beneficial endophyte of grapefruits that colonizes the fruit's peel, and protects
      it from CRM. SIGNIFICANCE AND IMPACT OF THE STUDY: Findings from this study
      demonstrate the endophytic nature of M. geulakonigii in its interaction with
      grapefruits. In addition, a molecular approach was developed to specifically
      detect the fungus inside the grapefruit peel. This approach can be used to assess
      the natural occurrence of M. geulakonigii in grapefruit.

PMID- 18045442
TI  - Molecular determination of oxytetracycline-resistant bacteria and their
      resistance genes from mariculture environments of China.
AB  - AIMS: To assess the diversity of antibiotic-resistant bacteria and their
      resistance genes in typical maricultural environments. METHODS AND RESULTS:
      Multidrug-resistant bacteria and resistance genes from a mariculture farm of
      China were analysed via cultivation and polymerase chain reaction (PCR) methods.
      Oxytetracycline (OTC)-resistant bacteria were abundant in both abalone and turbot
      rearing waters, accounting for 3.7% and 9.9% of the culturable microbes.
      Multidrug resistance was common, with simultaneous resistance to OTC,
      chloramphenicol and ampicillin the most common resistance phenotype. 16S rDNA
      sequence analyses indicate that the typical resistant isolates belonged to marine
      Vibrio, Pseudoalteromonas or Alteromonas species, with resistance most common in
      Vibrio splendidus isolates. For OTC resistance, tet(A), tet(B) and tet(M) genes
      were detected in some multidrug-resistant isolates, with tet(D) being the most
      common molecular determinant. For chloramphenicol resistance, cat II was common,
      and floR was also detected, especially in marine Pseudoalteromonas strains.
      CONCLUSIONS: There is the risk of multidrug-resistant bacteria contamination in
      mariculture environments and marine Vibrio and Pseudoalteromonas species serve as
      reservoirs of specific antibiotic resistance determinants. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This paper and similar findings from Korea and Japan
      indicate the potential for widespread distribution of antibiotic resistance genes
      in mariculture environments from the East Asian region of the world.

PMID- 18045443
TI  - Immigration of Bacillus thuringiensis to bean leaves from soil inoculum or distal
      plant parts.
AB  - AIMS: We addressed the process of immigration of Bacillus thuringiensis from soil
      to leaves and its capacity to grow on bean diffusate medium (BDM), a medium
      designed to simulate the nutrient composition of the phylloplane. METHODS AND
      RESULTS: Two different B. thuringiensis strains were inoculated into soils, onto
      seeds or onto lower leaves of bean plants to determine if they were able to
      disperse to upper leaves under controlled conditions. While B. thuringiensis
      isolates were commonly recovered from leaves exposed to such inocula, populations
      were very low (<10 CFU cm(-2) of leaf). In addition, the number of cells of B.
      thuringiensis recovered decreased with increasing distance from the soil or from
      the inoculated leaves. Moreover, B. thuringiensis colonies did not grow well on
      BDM. CONCLUSIONS: This indicates that B. thuringiensis disperses poorly from the
      soil or the seed to the leaves or between leaves of the same plant under
      controlled conditions. Bacillus thuringiensis apparently has greater nutrient
      requirements than other bacterial species that are prominent inhabitants of the
      phylloplane. SIGNIFICANCE AND IMPACT OF THE STUDY: Finding the mechanisms that
      favour bacteria colonization on leaves will in turn help to improve the efficacy
      of biocontrol agents against the target pests.

PMID- 18045444
TI  - Can the high levels of human verocytotoxigenic Escherichia coli O157 infection in
      rural areas of NE Scotland be explained by consumption of contaminated meat?
AB  - AIMS: To determine if contamination levels of Escherichia coli O157 and generic
      E. coli in retail-minced meat products are greater in rural shops compared with
      urban shops in Grampian, NE Scotland. We also investigated whether meat from
      supermarkets and meat from local butcher shops had a similar bacteriological
      quality. METHODS AND RESULTS: Minced beef and minced lamb were tested from
      November 2004 to August 2006. Escheichia coli O157 was found at low levels in
      four samples out of 530 tested samples (0.75%). Generic E. coli were present in
      11% of the samples tested, of which 67% came from supermarkets. We observed no
      significant difference in the prevalence of generic E. coli between rural and
      urban areas. CONCLUSIONS: Low levels of contamination with E. coli O157 and
      generic E. coli in retail meat suggest that meat is not a major route of
      infection in NE Scotland. SIGNIFICANCE AND IMPACT OF THE STUDY: The study does
      not suggest that the high incidence of E. coli O157 human infection in the rural
      areas of Grampian is because of meat consumption--this provides further evidence
      of contact with animals or water being the routes of infection. Hence, risk
      mitigation should be focussed more on environmental pathways of infection.

PMID- 18045445
TI  - Two different PCR approaches for universal diagnosis of brown rot and
      identification of Monilinia spp. in stone fruit trees.
AB  - AIMS: To design a protocol for the universal diagnosis of brown rot by polymerase
      chain reaction (PCR) in plant material and subsequently Monilinia spp.
      identification. METHODS AND RESULTS: Primers for discrimination of Monilinia spp.
      from other fungal genera by PCR were designed following a ribosomal DNA analysis.
      Discrimination among species of Monilinia was subsequently achieved by developing
      primers using SCAR (Sequence Characterised Amplified Region) markers obtained
      after a random amplified polymorphic DNA study. In addition, an internal control
      (IC) based on the utilization of a mimic plasmid was designed to be used in the
      diagnostic protocol of brown rot to recognize false negatives due to the
      inhibition of PCR. CONCLUSIONS: The four sets of primers designed allowed
      detection and discrimination of all Monilinia spp. causing brown rot in fruit
      trees. Addition of an IC in each PCR reaction performed increased the reliability
      of the diagnostic protocol. SIGNIFICANCE AND IMPACT OF THE STUDY: The detection
      protocol presented here, that combined a set of universal primers and the
      inclusion of the plasmid pGMON as an IC for diagnosis of all Monilinia spp., and
      three sets of primers to discriminate the most important species of Monilinia,
      could be an useful and valuable tool for epidemiological studies. The method
      developed could be used in programmes to avoid the spread and introduction of
      this serious disease in new areas.

PMID- 18045446
TI  - Diversity of the Lactobacillus group in breast milk and vagina of healthy women
      and potential role in the colonization of the infant gut.
AB  - AIMS: To evaluate the diversity of the Lactobacillus group in breast milk and the
      vagina of healthy women and understand their potential role in the infant gut
      colonization using the 16S rRNA gene approaches. METHODS AND RESULTS: Samples of
      breast milk, vaginal swabs and infant faeces were aseptically collected from five
      mothers whose neonates were born by vaginal delivery and another five that had
      their babies by caesarean section. After polymerase chain reaction (PCR)
      amplification using Lactobacillus group-specific primers, amplicons were analysed
      by denaturing gradient gel electrophoresis (DGGE). Clone libraries were
      constructed to describe the Lactobacillus group diversity. DGGE fingerprints were
      not related to the delivery method. None of the species detected in vaginal
      samples were found in breast milk-derived libraries and only few were detected in
      infant faeces. CONCLUSIONS: The bacterial composition of breast milk and infant
      faeces is not related to the delivery method. SIGNIFICANCE AND IMPACT OF THE
      STUDY: It has been suggested that neonates acquire lactobacilli by oral
      contamination with vaginal strains during delivery; subsequently, newborns would
      transmit such bacteria to the breast during breastfeeding. However, our findings
      confirm, at the molecular level that in contrast to the maternal vagina, breast
      milk seems to constitute a good source of lactobacilli to the infant gut.

PMID- 18045447
TI  - Mutational analysis of the Lactococcus lactis NIZO B40 exopolysaccharide (EPS)
      gene cluster: EPS biosynthesis correlates with unphosphorylated EpsB.
AB  - AIMS: To determine the role of the EpsA, EpsB, and EpsC proteins encoded at the
      5'-end of the exopolysaccharide (EPS) gene cluster in regulation of EPS
      production in Lactococcus lactis. METHODS AND RESULTS: Deletion and paralog
      replacement mutants of epsABCD were used to determine the function of EpsA, EpsB
      and EpsC in EPS production and polymer chain length determination in L. lactis.
      EpsA and EpsB appeared to be essential for EPS biosynthesis in L. lactis, while
      deletion of the phosphatase (EpsC) only had a minor effect on the EPS production
      level. Determination of the phosphorylation state of EpsB and analysis of a C
      terminally truncated EpsB variant indicate that EPS biosynthesis in L. lactis is
      driven by a nonphosphorylated form of EpsB. CONCLUSIONS: The data presented here
      show that in L. lactis, EPS production is under control of a phosphoregulatory
      system and that EPS biosynthesis correlates with an unphosphorylated EpsB.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides molecular understanding
      of polysaccharide production in L. lactis that could eventually enable novel
      approaches to control EPS production by lactic acid bacteria during industrial
      fermentation processes.

PMID- 18045448
TI  - Quantification by real-time PCR of cellulolytic bacteria in the rumen of sheep
      after supplementation of a forage diet with readily fermentable carbohydrates:
      effect of a yeast additive.
AB  - AIM: To examine the effect of concentrate and yeast additive on the number of
      cellulolytic bacteria in the rumen of sheep. METHODS AND RESULTS: Fibrobacter
      succinogenes, Ruminococcus albus and Ruminococcus flavefaciens were quantified
      using real-time PCR (targeting 16S rDNA) in parallel to cellulolytic flora
      enumeration with cultural techniques. Whatever the conditions tested, R.
      flavefaciens was slightly more abundant than F. succinogenes, with both species
      outnumbering R. albus. Before feeding, the shift from hay to hay plus concentrate
      diet had no effect on rumen pH and on the number of the three specie; while after
      feeding, the concentrate-supplemented diet induced a decrease (-1 log) of the
      number of the three species concomitant with the rumen acidification. Overall,
      the presence of the live yeast resulted in a significant increase (two- to
      fourfold) of the Ruminococci. CONCLUSION: The use of real-time PCR allowed us to
      show changes in the number of cellulolytic bacterial species in vivo in response
      to diet shift and additives that could not be as easily evidenced by classical
      microbial methods. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributes
      to the understanding of the negative impact of readily fermentable carbohydrates
      on rumen cellulolysis and the beneficial effect of yeast on rumen fermentation.

PMID- 18045449
TI  - Efficient removal of hexavalent chromium by a tolerant Streptomyces sp. affected
      by the toxic effect of metal exposure.
AB  - AIMS: To isolate and analyse chromium-resistant micro-organisms suitable for
      bioremediation. METHODS AND RESULTS: Strain CG252, with a minimal inhibitory
      concentration of 500 microg ml(-1), was isolated from contaminated soils and
      identified as a Streptomyces sp. by 16S rDNA sequence analysis. Assays carried
      out at various Cr(VI) concentrations indicated that chromium removal was more
      efficient at lower concentrations and that this activity resulted in accumulation
      of Cr(III). Atomic adsorption analysis indicated that the chromium removed was
      not associated with cell mass and activity assays showed that the capacity to
      reduce Cr(VI) was most probably due to a soluble cytosolic enzyme. Cells grown as
      biofilms showed enhanced removal of Cr(VI) with respect to planktonic cells,
      while analysis of growth and colony morphology indicated that Cr(VI) had a toxic
      effect on this strain. CONCLUSIONS: Streptomyces sp. CG252 tolerated heavy metals
      and elevated levels of chromium, despite its negative effect on growth and
      development, and was efficient at removing Cr(VI) by promoting reduction to
      Cr(III). SIGNIFICANCE AND IMPACT OF THE STUDY: Strain CG252's capacity to
      tolerate heavy metals and to reduce Cr(VI) to the less toxic Cr(III), especially
      when forming biofilms, makes it a promising candidate for detoxification of sites
      containing this heavy metal.

PMID- 18045450
TI  - Influence of avilamycin administration and its subsequent withdrawal on emergence
      and disappearance of antimicrobial resistance in enterococci in the intestine of
      broiler chickens.

PMID- 18045452
TI  - Acute isolated acetabular fracture following a game of squash: a case report.
AB  - Although hip injuries do not account a large amount of the Sports Physician's
      workload they can result in significant morbidity. We present a case where an
      acetabular fracture was sustained in a relatively young female while playing
      squash without any history of fall or injury but was treated successfully non
      operatively. Such patients who present with acute hip pain must not be dismissed
      as simply having a soft tissue injury.

PMID- 18045453
TI  - A comparative study between mixed-type tumours from human salivary and canine
      mammary glands.
AB  - BACKGROUND: In comparative pathology, canine mammary tumours have special
      interest because of their similarities with human breast cancer. Mixed tumours
      are uncommon lesions in the human breast, but they are found most frequently in
      the mammary gland of the female dogs and in the human salivary glands. The aim of
      the study was to compare clinical, morphological and immunohistochemical features
      of human salivary and canine mammary gland mixed tumours, in order to evaluate
      the latter as an experimental model for salivary gland tumours. METHODS: Ten
      examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex
      pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were
      evaluated. First, clinical and morphologic aspects of benign and malignant
      variants were compared between the species. Then, streptavidin-biotin-peroxidase
      immunohistochemistry was performed to detect the expression of cytokeratins,
      vimentin, p63 protein, estrogen receptor, beta-catenin, and E-cadherin. RESULTS:
      After standardization, similar age and site distributions were observed in human
      and canine tumours. Histological similarities were identified in the comparison
      of the benign lesions as well. Metaplastic carcinomas also resembled general
      aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation.
      Additionally, immunohistochemical staining further presented similar antigenic
      expression between lesions. CONCLUSION: There are many similar features between
      human salivary and canine mammary gland mixed tumours. This observation is of
      great relevance for those interested in the study and management of salivary
      gland tumours, since canine lesions may constitute useful comparative models for
      their investigations.

PMID- 18045454
TI  - Locally advanced leiomyosarcoma of the spleen. A case report and review of the
      literature.
AB  - BACKGROUND: Leiomyosarcomas are rare tumours, predominantly localized in the
      stomach, small intestine and retroperitoneum. Only one case of primary
      leiomyosarcoma of the spleen is described in human beings in literature. CASE
      PRESENTATION: We report a case of locally advanced primary leiomyosarcoma of the
      spleen in a 54 year-old woman, diagnosed only after splenectomy, performed with
      the suspicion of splenic haematoma. CONCLUSION: Due to the lack of cases, no
      specific chemotherapy regimen has been tested to provide a longer survival.

PMID- 18045455
TI  - Bioinformatic evaluation of L-arginine catabolic pathways in 24 cyanobacteria and
      transcriptional analysis of genes encoding enzymes of L-arginine catabolism in
      the cyanobacterium Synechocystis sp. PCC 6803.
AB  - BACKGROUND: So far very limited knowledge exists on L-arginine catabolism in
      cyanobacteria, although six major L-arginine-degrading pathways have been
      described for prokaryotes. Thus, we have performed a bioinformatic analysis of
      possible L-arginine-degrading pathways in cyanobacteria. Further, we chose
      Synechocystis sp. PCC 6803 for a more detailed bioinformatic analysis and for
      validation of the bioinformatic predictions on L-arginine catabolism with a
      transcript analysis. RESULTS: We have evaluated 24 cyanobacterial genomes of
      freshwater or marine strains for the presence of putative L-arginine-degrading
      enzymes. We identified an L-arginine decarboxylase pathway in all 24 strains. In
      addition, cyanobacteria have one or two further pathways representing either an
      arginase pathway or L-arginine deiminase pathway or an L-arginine
      oxidase/dehydrogenase pathway. An L-arginine amidinotransferase pathway as a
      major L-arginine-degrading pathway is not likely but can not be entirely
      excluded. A rather unusual finding was that the cyanobacterial L-arginine
      deiminases are substantially larger than the enzymes in non-photosynthetic
      bacteria and that they are membrane-bound. A more detailed bioinformatic analysis
      of Synechocystis sp. PCC 6803 revealed that three different L-arginine-degrading
      pathways may in principle be functional in this cyanobacterium. These are (i) an
      L-arginine decarboxylase pathway, (ii) an L-arginine deiminase pathway, and (iii)
      an L-arginine oxidase/dehydrogenase pathway. A transcript analysis of cells grown
      either with nitrate or L-arginine as sole N-source and with an illumination of 50
      mumol photons m-2 s-1 showed that the transcripts for the first enzyme(s) of all
      three pathways were present, but that the transcript levels for the L-arginine
      deiminase and the L-arginine oxidase/dehydrogenase were substantially higher than
      that of the three isoenzymes of L-arginine decarboxylase. CONCLUSION: The
      evaluation of 24 cyanobacterial genomes revealed that five different L-arginine
      degrading pathways are present in the investigated cyanobacterial species. In
      Synechocystis sp. PCC 6803 an L-arginine deiminase pathway and an L-arginine
      oxidase/dehydrogenase pathway represent the major pathways, while the L-arginine
      decarboxylase pathway most likely only functions in polyamine biosynthesis. The
      transcripts encoding the enzymes of the two major pathways were constitutively
      expressed with the exception of the transcript for the carbamate kinase, which
      was substantially up-regulated in cells grown with L-arginine.

PMID- 18045456
TI  - Prolactin, TNF alpha and nitric oxide expression in nitroso-N-methylurea-induced
      mammary tumours.
AB  - BACKGROUND: The N-Nitrosomethylurea breast cancer model induced in rats is used
      for the study of carcinogenesis in mammary cancer, prostate, pancreas, etc. This
      model is very similar to human neoplastic disease. METHODS: The present
      experimental study was designed to assess whether metoclopramide administration
      has any effect on development of MNU-induced tumours, and evaluate the treatment
      of goserelin acetate on PRL, TNF alpha and NO expression. NMU was administered to
      female Wistar rats on 2 occasions (5 mg/100 g body w/rat). PRL and TNF alpha were
      performed by immune-assay. Nitric Oxide by semi automated-assay and ploidy
      analyses by flow cytometry. RESULTS: The administration of metoclopramide made
      the induction time shorter and increased the incidence and average of tumours per
      rat. Tumours development was inhibited by a goserelin chronic administration. The
      ploidy of adenocarcinoma was polyploid-aneuploid type (average S = 60%). It was
      higher basal PRL plasma levels in rats with NMU induced tumours than in basal
      controls without tumour (p < 0.001). The goserelin "in bolus" administration
      showed maximal inhibition of plasma PRL at 90 min. Plasmatic TNF alpha expression
      was inhibited at 60 min and also remained inhibited in tissue homogenate post
      chronic treatment (P < 0.0125). Plasmatic NO expression is higher in rats with
      induced tumours than healthy controls (P < 0.001). In tissue homogenate NO values
      were inhibited at 90 min (P < 0.01), as well during chronically goserelin
      treatment (P < 0.005). CONCLUSION: The increase of blood PRL levels in NMU
      induced rats may be an indicator of a poor prognosis of mammary cancer evolution.
      The metoclopramide administration accelerates tumour growth. However goserelin
      administration achieves regression in tumour development associated to inhibition
      PRL, TNF alpha and NO expression.

PMID- 18045457
TI  - Kinesiophobia in patients with non-traumatic arm, neck and shoulder complaints: a
      prospective cohort study in general practice.
AB  - BACKGROUND: Complaints of arm, neck and shoulder are common in Western societies.
      Of those consulting a general practitioner (GP) with non-traumatic arm, neck or
      shoulder complaints, about 50% do not recover within 6 months. Kinesiophobia
      (also known as fear of movement/(re)injury) may also play a role in these
      complaints, as it may lead to avoidance behaviour resulting in hypervigilance to
      bodily sensations, followed by disability, disuse and depression. However, in
      relation to arm, neck and shoulder complaints little is known about kinesiophobia
      and its associated variables. Therefore this study aimed to: describe the degree
      of kinesiophobia in patients with non-traumatic complaints of arm, neck and
      shoulder in general practice; to determine whether mean scores of kinesiophobia
      change over time in non-recovered patients; and to evaluate variables associated
      with kinesiophobia at baseline. METHODS: In this prospective cohort study set in
      general practice, consulters with a first or new episode of non-traumatic arm,
      neck or shoulder complaints (aged 18-64 years) entered the cohort. Baseline data
      were collected on kinesiophobia using the Tampa Scale for Kinesiophobia, the 13
      item adjusted version: TSK-AV, and on patient-, complaint-, and psychosocial
      variables using self-administered questionnaires. The mean TSK-AV score was
      calculated. In non-recovered patients the follow-up TSK-AV scores at 6 and 12
      months were analyzed with the general linear mixed model. Variables associated
      with kinesiophobia at baseline were evaluated using multivariate linear
      regression analyses. RESULTS: The mean TSK-AV score at baseline was 24.8 [SD:
      6.2]. Among non-recovered patients the mean TSK-AV score at baseline was 26.1
      [SD: 6.6], which remained unchanged over 12- months follow-up period. The
      strongest associations with kinesiophobia were catastrophizing, disability, and
      comorbidity of musculoskeletal complaints. Additionally, having a shoulder
      complaint, low social support, high somatization and high distress contributed to
      the kinesiophobia score. CONCLUSION: The mean TSK-AV score in our population
      seems comparable to those in other populations in primary care. In patients who
      did not recover during the 12- month follow-up, the degree of kinesiophobia
      remained unchanged during this time period. The variables associated with
      kinesiophobia at baseline appear to be in line with the fear-avoidance model.

PMID- 18045458
TI  - Assessing fetal growth impairments based on family data as a tool for identifying
      high-risk babies. An example with neonatal mortality.
AB  - BACKGROUND: Low birth weight is associated with an increased risk of neonatal and
      infant mortality and morbidity, as well as with other adverse conditions later in
      life. Since the birth weight-specific mortality of a second child depends on the
      birth weight of an older sibling, a failure to achieve the biologically intended
      size appears to increase the risk of adverse outcome even in babies who are not
      classified as small for gestation. In this study, we aimed at quantifying the
      risk of neonatal death as a function of a baby's failure to fulfil its biologic
      growth potential across the whole distribution of birth weight. METHODS: We
      predicted the birth weight of 411,957 second babies born in Denmark (1979-2002),
      given the birth weight of the first, and examined how the ratio of achieved birth
      weight to predicted birth weight performed in predicting neonatal mortality.
      RESULTS: For any achieved birth weight category, the risk of neonatal death
      increased with decreasing birth weight ratio. However, the risk of neonatal death
      increased with decreasing birth weight, even among babies who achieved their
      predicted birth weight. CONCLUSION: While a low achieved birth weight was a
      stronger predictor of mortality, a failure to achieve the predicted birth weight
      was associated with increased mortality at virtually all birth weights. Use of
      family data may allow identification of children at risk of adverse health
      outcomes, especially among babies with apparently "normal" growth.

PMID- 18045459
TI  - Spleen tyrosine kinase Syk is critical for sustained leukocyte adhesion during
      inflammation in vivo.
AB  - BACKGROUND: During inflammation, beta2-integrins mediate leukocyte adhesion to
      the endothelium accompanied by the activation of the spleen tyrosine kinase Syk.
      RESULTS: We investigated leukocyte adhesion and rolling in cremaster muscle
      venules before and during stimulation with fMLP using mice with a Syk-/-
      hematopoietic system. In unstimulated venules, Syk-/- leukocytes adhered less
      efficiently than control leukocytes while rolling was similar between Syk-/- and
      control leukocytes. During fMLP-superfusion, control mice showed significantly
      increased adhesion accompanied by reduced rolling. For Syk-/- leukocytes, an
      increase in adhesion with a concomitant decrease in rolling was only observed
      during the first three minutes during fMLP stimulation, but not at later time
      points. We also investigated leukocyte spreading against the vessel wall during
      fMLP stimulation and found a significant impairment of spreading for Syk-/-
      leukocytes. Additional in vitro experiments revealed that the adhesion and
      spreading defect seen in Syk-/- chimeric mice was due to compromised beta2
      integrin-mediated outside-in signaling. CONCLUSION: We provide substantial
      evidence for an important role of Syk in mediating beta2-integrin dependent
      outside-in signaling leading to sustained leukocyte adhesion and spreading during
      the inflammatory response in vivo.

PMID- 18045460
TI  - Homocysteine levels in preterm infants: is there an association with
      intraventricular hemorrhage? A prospective cohort study.
AB  - BACKGROUND: The purpose of this study was to characterize total homocysteine
      (tHcy) levels at birth in preterm and term infants and identify associations with
      intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality,
      sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and
      thrombocytopenia. METHODS: 123 infants < 32 weeks gestation admitted to our Level
      III nursery were enrolled. A group of 25 term infants were enrolled for
      comparison. Two blood spots collected on filter paper with admission blood
      drawing were analyzed by a high performance liquid chromatography (HPLC) method.
      Statistical analysis included ANOVA, Spearman's Rank Order Correlation and Mann
      Whitney U test. RESULTS: The median tHcy was 2.75 micromol/L with an
      interquartile range of 1.34 - 4.96 micromol/L. There was no difference between
      preterm and term tHcy (median 2.76, IQR 1.25 - 4.8 micromol/L vs median 2.54, IQR
      1.55 - 7.85 micromol/L, p = 0.07). There was no statistically significant
      difference in tHcy in 31 preterm infants with IVH compared to infants without IVH
      (median 1.96, IQR 1.09 - 4.35 micromol/L vs median 2.96, IQR 1.51 - 4.84
      micromol/L, p = 0.43). There was also no statistically significant difference in
      tHcy in 7 infants with periventricular leukomalacia (PVL) compared to infants
      without PVL (median 1.55, IQR 0.25 - 3.45 micromol/L vs median 2.85, IQR 1.34 -
      4.82 micromol/L, p = 0.07). Male infants had lower tHcy compared to female;
      prenatal steroids were associated with a higher tHcy. CONCLUSION: In our
      population of preterm infants, there is no association between IVH and tHcy. Male
      gender, prenatal steroids and preeclampsia were associated with differences in
      tHcy levels.

PMID- 18045461
TI  - Cost-utility analysis of a national project to reduce hypertension in Israel.
AB  - BACKGROUND: This study aims to calculate the health effects and costs of a
      proposed national hypertension prevention and control program. METHODS:
      Interventions are based on experience from our two programs: 10-year period of
      Ashkelon Hypertension Detection and Control Program (AHDC Program) and the Israel
      Blood Pressure Control (IBPC) program. The costs of a nationwide program were
      calculated based on economic data, training staff levels, course frequency and
      unit costs. RESULTS: Over the next 20 years, the program should decrease the risk
      in one-half of the treated hypertensive cases of the following ailments:
      cardiovascular events such as Acute Myocardial Infarction (AMI) and Unstable
      Angina Pectoris (UAP) by 16.0%, stroke by 41.2%, End stage renal disease (ESRD)
      by 50.0% and peripheral vascular disease (PVD) by 42.6%. In total, around 2,242
      lives, 35,117 years of life or 24,433 disability adjusted life years will be
      saved due to decreased mortality.Program costs amount to $352.7 million. However
      savings ($537.6 million), from reduced medical treatment ($444.3 million) and
      reduced pharmaceutical use ($93.3 million) as a result of morbidity decreases,
      exceed costs by $185.0 million. CONCLUSION: The project which saves both lives
      and resources should be extended nation-wide to reach as wide a population as
      possible.

PMID- 18045463
TI  - Jejunal perforation in gallstone ileus - a case series.
AB  - INTRODUCTION: Gallstone ileus is an uncommon complication of cholelithiasis but
      an established cause of mechanical bowel obstruction in the elderly. Perforation
      of the small intestine proximal to the obstructing gallstone is rare, and only a
      handful of cases have been reported. We present two cases of perforation of the
      jejunum in gallstone ileus, and remarkably in one case, the gallstone ileus
      caused perforation of a jejunal diverticulum and is to the best of our knowledge
      the first such case to be described. CASE PRESENTATIONS: Case 1A 69 year old man
      presented with two days of vomiting and central abdominal pain. He underwent
      laparotomy for small bowel obstruction and was found to have a gallstone
      obstructing the mid-ileum. There was a 2 mm perforation in the anti-mesenteric
      border of the dilated proximal jejunum. The gallstone was removed and the
      perforated segment of jejunum was resected.Case 2A 68 year old man presented with
      a four day history of vomiting and central abdominal pain. Chest and abdominal
      radiography were unremarkable however a subsequent CT scan of the abdomen showed
      aerobilia. At laparotomy his distal ileum was found to be obstructed by an
      impacted gallstone and there was a perforated diverticulum on the mesenteric
      surface of the mid-jejunum. An enterolithotomy and resection of the perforated
      small bowel was performed. CONCLUSION: Gallstone ileus remains a diagnostic
      challenge despite advances in imaging techniques, and pre-operative diagnosis is
      often delayed. Partly due to the elderly population it affects, gallstone ileus
      continues to have both high morbidity and mortality rates. On reviewing the
      literature, the most appropriate surgical intervention remains unclear.Jejunal
      perforation in gallstone ileus is extremely rare. The cases described illustrate
      two quite different causes of perforation complicating gallstone ileus. In the
      first case, perforation was probably due to pressure necrosis caused by the
      gallstone. The second case was complicated by the presence of a perforated
      jejunal diverticulum, which was likely to have been secondary to the increased
      intra-luminal pressure proximal to the obstructing gallstone.These cases should
      raise awareness of the complications associated with both gallstone ileus, and
      small bowel diverticula.

PMID- 18045462
TI  - Integrative analysis for finding genes and networks involved in diabetes and
      other complex diseases.
AB  - We have developed an integrative analysis method combining genetic interactions,
      identified using type 1 diabetes genome scan data, and a high-confidence human
      protein interaction network. Resulting networks were ranked by the significance
      of the enrichment of proteins from interacting regions. We identified a number of
      new protein network modules and novel candidate genes/proteins for type 1
      diabetes. We propose this type of integrative analysis as a general method for
      the elucidation of genes and networks involved in diabetes and other complex
      diseases.

PMID- 18045464
TI  - Cytokine responses to Schistosoma haematobium in a Zimbabwean population:
      contrasting profiles for IFN-gamma, IL-4, IL-5 and IL-10 with age.
AB  - BACKGROUND: The rate of development of parasite-specific immune responses can be
      studied by following their age profiles in exposed and infected hosts. This study
      determined the cytokine-age profiles of Zimbabweans resident in a Schistosoma
      haematobium endemic area and further investigated the relationship between the
      cytokine responses and infection intensity. METHODS: Schistosome adult worm
      antigen-specific IFN-gamma, IL-4, IL-5 and IL-10 cytokine responses elicited from
      whole blood cultures were studied in 190 Zimbabweans exposed to S. haematobium
      infection (aged 6 to 40 years old). The cytokines were measured using capture
      ELISAs and the data thus obtained together with S. haematobium egg count data
      from urine assays were analysed using a combination of parametric and
      nonparametric statistical approaches. RESULTS: Age profiles of schistosome
      infection in the study population showed that infection rose to peak in childhood
      (11-12 years) followed by a sharp decline in infection intensity while prevalence
      fell more gradually. Mean infection intensity was 37 eggs/10 ml urine (SE 6.19
      eggs/10 ml urine) while infection prevalence was 54.7%. Measurements of parasite
      specific cytokine responses showed that IL-4, IL-5 and IL-10 but not IFN-gamma
      followed distinct age-profiles. Parasite-specific IL-10 production developed
      early, peaking in the youngest age group and declining thereafter; while IL-4 and
      IL-5 responses were slower to develop with a later peak. High IL-10 producers
      were likely to be egg positive with IL-10 production increasing with increasing
      infection intensity. Furthermore people producing high levels of IL-10 produced
      little or no IL-5, suggesting that IL-10 may be involved in the regulation of IL
      5 levels. IL-4 and IFN-gamma did not show a significant relationship with
      infection status or intensity and were positively associated with each other.
      CONCLUSION: Taken together, these results show that the IL-10 responses develop
      early compared to the IL-5 response and may be down-modulating immunopathological
      responses that occur during the early phase of infection. The results further
      support current suggestions that the Th1/Th2 dichotomy does not sufficiently
      explain susceptibility or resistance to schistosome infection.

PMID- 18045465
TI  - Disease proportions attributable to environment.
AB  - Population disease proportions attributable to various causal agents are popular
      as they present a simplified view of the contribution of each agent to the
      disease load. However they are only summary figures that may be easily
      misinterpreted or over-interpreted even when the causal link between an exposure
      and an effect is well established. This commentary discusses several issues
      surrounding the estimation of attributable proportions, particularly with
      reference to environmental causes of cancers, and critically examines two
      recently published papers. These issues encompass potential biases as well as the
      very definition of environment and of environmental agent. The latter aspect is
      not just a semantic question but carries implications for the focus of preventive
      actions, whether centred on the material and social environment or on single
      individuals.

PMID- 18045466
TI  - Enhanced transduction of colonic cell lines in vitro and the inflamed colon in
      mice by viral vectors, derived from adeno-associated virus serotype 2, using
      virus-microbead conjugates bearing lectin.
AB  - BACKGROUND: Virus-mediated delivery of therapeutic transgenes to the inflamed
      colon holds a great potential to serve as an effective therapeutic strategy for
      inflammatory bowel disease, since local, long-term expression of the encoded
      therapeutic proteins in the colorectal system is potentially achievable. Viral
      vectors, derived from adeno-associated virus (AAV), should be very useful for
      such therapeutic strategies, particularly because they can establish long-term
      expression of transgenes. However, few studies have been carried out to
      investigate the ability of AAV-based vectors to transduce the inflamed colon.
      RESULTS: AAV, derived from adeno-associated virus serotype 2 (AAV2), showed a
      limited ability to transduce colonic cell lines in vitro when used in free form.
      No appreciable enhancement of the transduction efficiency was seen when AAV2
      particles were attached stably to the surfaces of microbeads and delivered to
      target cells in the form of AAV2-microbead conjugates. However, the transduction
      efficiency of these colonic cell lines was enhanced substantially when a lectin,
      concanavalin A (Con A), was co-attached to the microbead surfaces, to which AAV2
      particles had been conjugated. This considerable infectivity enhancement of AAV2
      microbead conjugates by the co-attachment of Con A may be derived from the fact
      that Con A binds to alpha-D-mannosyl moieties that are commonly and abundantly
      present in cell-surface carbohydrate chains, allowing the conjugates to associate
      stably with target cells. Intracolonical administration of free AAV2 or AAV2
      microbead conjugates without Con A into a mouse colitis model by enema showed
      very poor transduction of the colonic tissue. In contrast, the delivery of AAV2
      in the form of AAV2-microbead conjugates bearing Con A resulted in efficient
      transduction of the inflamed colon. CONCLUSION: AAV2-microbead conjugates bearing
      Con A can serve as efficient gene transfer agents both for poorly permissive
      colonic cell lines in vitro and for the inflamed colon in a mouse colitis model.
      This efficient transduction system for the inflamed colon should be useful for
      the development of gene therapy strategies for inflammatory bowel disease.

PMID- 18045467
TI  - A flexible routing scheme for patients with topographical disorientation.
AB  - BACKGROUND: Individuals with topographical disorientation have difficulty
      navigating through indoor environments. Recent literature has suggested that
      ambient intelligence technologies may provide patients with navigational
      assistance through auditory or graphical instructions delivered via embedded
      devices. METHOD: We describe an automatic routing engine for such an ambient
      intelligence system. The method routes patients with topographical disorientation
      through indoor environments by repeatedly computing the route of minimal cost
      from the current location of the patient to a specified destination. The cost of
      a given path not only reflects the physical distance between end points, but also
      incorporates individual patient abilities, the presence of mobility-impeding
      physical barriers within a building and the dynamic nature of the indoor
      environment. We demonstrate the method by routing simulated patients with either
      topographical disorientation or physical disabilities. Additionally, we exemplify
      the ability to route a patient from source to destination while taking into
      account changes to the building interior. RESULTS: When compared to a random
      walk, the proposed routing scheme offers potential cost-savings even when the
      patient follows only a subset of instructions. CONCLUSION: The routing method
      presented reduces the navigational effort for patients with topographical
      disorientation in indoor environments, accounting for physical abilities of the
      patient, environmental barriers and dynamic building changes. The routing
      algorithm and database proposed could be integrated into wearable and mobile
      platforms within the context of an ambient intelligence solution.

PMID- 18045468
TI  - Dynamic gene expression in fish muscle during recovery growth induced by a
      fasting-refeeding schedule.
AB  - BACKGROUND: Recovery growth is a phase of rapid growth that is triggered by
      adequate refeeding of animals following a period of weight loss caused by
      starvation. In this study, to obtain more information on the system-wide
      integration of recovery growth in muscle, we undertook a time-course analysis of
      transcript expression in trout subjected to a food deprivation-refeeding
      sequence. For this purpose complex targets produced from muscle of trout fasted
      for one month and from muscle of trout fasted for one month and then refed for 4,
      7, 11 and 36 days were hybridized to cDNA microarrays containing 9023 clones.
      RESULTS: Significance analysis of microarrays (SAM) and temporal expression
      profiling led to the segregation of differentially expressed genes into four
      major clusters. One cluster comprising 1020 genes with high expression in muscle
      from fasted animals included a large set of genes involved in protein catabolism.
      A second cluster that included approximately 550 genes with transient induction 4
      to 11 days post-refeeding was dominated by genes involved in transcription,
      ribosomal biogenesis, translation, chaperone activity, mitochondrial production
      of ATP and cell division. A third cluster that contained 480 genes that were up
      regulated 7 to 36 days post-refeeding was enriched with genes involved in
      reticulum and Golgi dynamics and with genes indicative of myofiber and muscle
      remodelling such as genes encoding sarcomeric proteins and matrix compounds.
      Finally, a fourth cluster of 200 genes overexpressed only in 36-day refed trout
      muscle contained genes with function in carbohydrate metabolism and lipid
      biosynthesis. Remarkably, among the genes induced were several transcriptional
      regulators which might be important for the gene-specific transcriptional
      adaptations that underlie muscle recovery. CONCLUSION: Our study is the first
      demonstration of a coordinated expression of functionally related genes during
      muscle recovery growth. Furthermore, the generation of a useful database of novel
      genes associated with muscle recovery growth will allow further investigations on
      particular genes, pathways or cellular process involved in muscle growth and
      regeneration.

PMID- 18045470
TI  - Breast MRI in nonpalpable breast lesions: a randomized trial with diagnostic and
      therapeutic outcome - MONET - study.
AB  - BACKGROUND: In recent years there has been an increasing interest in MRI as a non
      invasive diagnostic modality for the work-up of suspicious breast lesions. The
      additional value of Breast MRI lies mainly in its capacity to detect multicentric
      and multifocal disease, to detect invasive components in ductal carcinoma in situ
      lesions and to depict the tumor in a 3-dimensional image. Breast MRI therefore
      has the potential to improve the diagnosis and provide better preoperative
      staging and possibly surgical care in patients with breast cancer. The aim of our
      study is to assess whether performing contrast enhanced Breast MRI can reduce the
      number of surgical procedures due to better preoperative staging and whether a
      subgroup of women with suspicious nonpalpable breast lesions can be identified in
      which the combination of mammography, ultrasound and state-of-the-art contrast
      enhanced Breast MRI can provide a definite diagnosis. METHODS/DESIGN: The MONET -
      study (MR mammography Of Nonpalpable BrEast Tumors) is a randomized controlled
      trial with diagnostic and therapeutic endpoints. We aim to include 500 patients
      with nonpalpable suspicious breast lesions who are referred for biopsy. With this
      number of patients, the expected 12% reduction in surgical procedures due to more
      accurate preoperative staging with Breast MRI can be detected with a high power
      (90%). The secondary outcome is the positive and negative predictive value of
      contrast enhanced Breast MRI. If the predictive values are deemed sufficiently
      close to those for large core biopsy then the latter, invasive, procedure could
      possibly be avoided in some women. The rationale, study design and the baseline
      characteristics of the first 100 included patients are described. TRIAL
      REGISTRATION: Study protocol number NCT00302120.

PMID- 18045469
TI  - DprA/Smf protein localizes at the DNA uptake machinery in competent Bacillus
      subtilis cells.
AB  - BACKGROUND: DprA is a widely conserved bacterial protein and has been shown to
      confer an important function during transformation in competent cells, possibly
      through protection of incoming DNA. B. subtilis DprA (called Smf) and has been
      shown to play an important role during transformation with chromosomal DNA, but
      its mode of action is unknown. RESULTS: We show that B. subtilis DprA/Smf is more
      important for transformation with plasmid DNA than with chromosomal DNA. A
      functional Smf-YFP fusion localized as discrete foci to the cell pole in a subset
      of cells grown to competence, dependent on the ComK master transcription factor.
      Smf-YFP foci colocalized with ComGA-CFP. However, a considerable number of cells
      having high ComK activity contained Smf dispersed throughout the cytosol and
      lacked a polar Smf assembly. The absence of polar Smf-YFP foci in these cells
      strongly correlated with the absence of ComGA-CFP foci, and comGA mutant cells
      mostly lacked polar Smf-YFP foci. Smf formed polar assemblies in the absence of
      RecA, and RecA formed dynamic threads after addition of DNA in a smf deletion
      strain. Upon addition of DNA, Smf-YFP foci relocalized from the poles to the cell
      centre, dependent on the presence of RecA protein. CONCLUSION: Our data show that
      Smf is recruited to the polar competence machinery, and that polar Smf assembly
      requires a functional DNA uptake complex. High ComK levels drive expression of
      Smf in 20% of all cells grown to competence, but not all competent cells contain
      a polar DNA uptake machinery, showing that ComK activity is necessary but not
      sufficient to achieve assembly of the uptake machinery in all cells. Smf and RecA
      localize independently of each other, in agreement with our finding that Smf is
      much more important for plasmid transformation than RecA, but RecA influences the
      dynamic localization pattern of Smf. Our data show that DprA/Smf acts downstream
      of the DNA uptake machinery, and support the idea that Smf protects incoming
      ssDNA, possibly in conjunction with RecA.

PMID- 18045471
TI  - Breastfeeding and childhood asthma: a six-year population-based cohort study.
AB  - BACKGROUND: The question of the protective effect of breastfeeding on development
      of asthma has raised substantial interest, but the scientific evidence of the
      optimal duration of breastfeeding is controversial. METHODS: The authors
      elaborated the optimal duration of breastfeeding with respect to the risk of
      asthma primarily, and secondarily to the risk of persistent wheezing, cough and
      phlegm in school age in a population-based cohort study with the baseline in 1991
      and follow-up in 1997. The study population comprised 1984 children aged 7 to 14
      years at the end of the follow-up (follow-up rate 77). Information on
      breastfeeding was based on the baseline survey and information on the health
      outcomes at the follow-up. RESULTS: There was a U-shaped relation between
      breastfeeding and the outcomes with the lowest risk with breastfeeding from four
      to nine months for asthma and seven to nine months for persistent wheezing, cough
      and phlegm. CONCLUSION: Our results suggest a U shape relation between duration
      of breastfeeding and risk of asthma with an optimal duration of 4 to 6 months. A
      true concave relation would explain the inconsistent results from the previous
      studies.

PMID- 18045472
TI  - How many mailouts? Could attempts to increase the response rate in the Iraq war
      cohort study be counterproductive?
AB  - BACKGROUND: Low response and reporting errors are major concerns for survey
      epidemiologists. However, while nonresponse is commonly investigated, the effects
      of misclassification are often ignored, possibly because they are hard to
      quantify. We investigate both sources of bias in a recent study of the effects of
      deployment to the 2003 Iraq war on the health of UK military personnel, and
      attempt to determine whether improving response rates by multiple mailouts was
      associated with increased misclassification error and hence increased bias in the
      results. METHODS: Data for 17,162 UK military personnel were used to determine
      factors related to response and inverse probability weights were used to assess
      nonresponse bias. The percentages of inconsistent and missing answers to health
      questions from the 10,234 responders were used as measures of misclassification
      in a simulation of the 'true' relative risks that would have been observed if
      misclassification had not been present. Simulated and observed relative risks of
      multiple physical symptoms and post-traumatic stress disorder (PTSD) were
      compared across response waves (number of contact attempts). RESULTS: Age, rank,
      gender, ethnic group, enlistment type (regular/reservist) and contact address
      (military or civilian), but not fitness, were significantly related to response.
      Weighting for nonresponse had little effect on the relative risks. Of the
      respondents, 88% had responded by wave 2. Missing answers (total 3%) increased
      significantly (p < 0.001) between waves 1 and 4 from 2.4% to 7.3%, and the
      percentage with discrepant answers (total 14%) increased from 12.8% to 16.3% (p =
      0.007). However, the adjusted relative risks decreased only slightly from 1.24 to
      1.22 for multiple physical symptoms and from 1.12 to 1.09 for PTSD, and showed a
      similar pattern to those simulated. CONCLUSION: Bias due to nonresponse appears
      to be small in this study, and increasing the response rates had little effect on
      the results. Although misclassification is difficult to assess, the results
      suggest that bias due to reporting errors could be greater than bias caused by
      nonresponse. Resources might be better spent on improving and validating the
      data, rather than on increasing the response rate.

PMID- 18045473
TI  - The metal tolerance profile of Thlaspi goesingense is mimicked in Arabidopsis
      thaliana heterologously expressing serine acetyl-transferase.
AB  - BACKGROUND: The Ni hyperaccumulator Thlaspi goesingense is tolerant to Ni
      congruent with Zn, congruent with Co and slightly resistant to > Cd. We
      previously observed that elevated glutathione, driven by constitutive activation
      of serine acetyltransferase (SAT), plays a role in the Ni tolerance of T.
      goesingense. RESULTS: Here we show that the elevated shoot concentration of
      glutathione, previously shown to cause elevated Ni tolerance in Arabidopsis
      thaliana heterologously expressing T. goesingense mitochondrial serine
      acetyltransferase (SATm), also causes tolerance to Co and Zn while slightly
      enhancing resistance to Cd. The level of tolerance afforded to each metal is
      ranked Ni congruent with Co, > Zn > Cd. The Ni congruent with Co, > Zn tolerances
      are positively correlated with both the accumulation of glutathione (GSH) and the
      ability to resist the oxidative damage induced by these different metals. Based
      on the relative concentrations of each metal used a relatively low level of
      resistance to Cd was observed in both T. goesingense and TgSATm expressing lines
      and Cd resistance was least correlated to GSH accumulation. CONCLUSION: Such data
      supports the conclusion that elevated glutathione levels, driven by
      constitutively enhanced SAT activity in the hyperaccumulator T. goesingense,
      plays an important role in the Ni, Co and Zn tolerance of this and other Thlaspi
      species. The hyper-activation of S assimilation through SAT is an excellent
      strategy for engineering enhanced metal tolerance in transgenic plants
      potentially used for phytoremediation.

PMID- 18045474
TI  - Pancreatic Expression database: a generic model for the organization, integration
      and mining of complex cancer datasets.
AB  - BACKGROUND: Pancreatic cancer is the 5th leading cause of cancer death in both
      males and females. In recent years, a wealth of gene and protein expression
      studies have been published broadening our understanding of pancreatic cancer
      biology. Due to the explosive growth in publicly available data from multiple
      different sources it is becoming increasingly difficult for individual
      researchers to integrate these into their current research programmes. The
      Pancreatic Expression database, a generic web-based system, is aiming to close
      this gap by providing the research community with an open access tool, not only
      to mine currently available pancreatic cancer data sets but also to include their
      own data in the database. DESCRIPTION: Currently, the database holds 32 datasets
      comprising 7636 gene expression measurements extracted from 20 different
      published gene or protein expression studies from various pancreatic cancer
      types, pancreatic precursor lesions (PanINs) and chronic pancreatitis. The
      pancreatic data are stored in a data management system based on the BioMart
      technology alongside the human genome gene and protein annotations, sequence,
      homologue, SNP and antibody data. Interrogation of the database can be achieved
      through both a web-based query interface and through web services using combined
      criteria from pancreatic (disease stages, regulation, differential expression,
      expression, platform technology, publication) and/or public data (antibodies,
      genomic region, gene-related accessions, ontology, expression patterns, multi
      species comparisons, protein data, SNPs). Thus, our database enables connections
      between otherwise disparate data sources and allows relatively simple navigation
      between all data types and annotations. CONCLUSION: The database structure and
      content provides a powerful and high-speed data-mining tool for cancer research.
      It can be used for target discovery i.e. of biomarkers from body fluids,
      identification and analysis of genes associated with the progression of cancer,
      cross-platform meta-analysis, SNP selection for pancreatic cancer association
      studies, cancer gene promoter analysis as well as mining cancer ontology
      information. The data model is generic and can be easily extended and applied to
      other types of cancer. The database is available online with no restrictions for
      the scientific community at http://www.pancreasexpression.org/.

PMID- 18045475
TI  - Carbohydrate restriction and dietary cholesterol modulate the expression of HMG
      CoA reductase and the LDL receptor in mononuclear cells from adult men.
AB  - The liver is responsible for controlling cholesterol homeostasis in the body. HMG
      CoA reductase and the LDL receptor (LDL-r) are involved in this regulation and
      are also ubiquitously expressed in all major tissues. We have previously shown in
      guinea pigs that there is a correlation in gene expression of HMG-CoA reductase
      and the LDL-r between liver and mononuclear cells. The present study evaluated
      human mononuclear cells as a surrogate for hepatic expression of these genes. The
      purpose was to evaluate the effect of dietary carbohydrate restriction with low
      and high cholesterol content on HMG-CoA reductase and LDL-r mRNA expression in
      mononuclear cells. All subjects were counseled to consume a carbohydrate
      restricted diet with 10-15% energy from carbohydrate, 30-35% energy from protein
      and 55-60% energy from fat. Subjects were randomly assigned to either EGG (640
      mg/d additional dietary cholesterol) or SUB groups [equivalent amount of egg
      substitute (0 dietary cholesterol contributions) per day] for 12 weeks. At the
      end of the intervention, there were no changes in plasma total or LDL cholesterol
      (LDL-C) compared to baseline (P > 0.10) or differences in plasma total or LDL-C
      between groups. The mRNA abundance for HMG-CoA reductase and LDL-r were measured
      in mononuclear cells using real time PCR. The EGG group showed a significant
      decrease in HMG-CoA reductase mRNA (1.98 +/- 1.26 to 1.32 +/- 0.92 arbitrary
      units P < 0.05) while an increase was observed for the SUB group (1.13 +/- 0.52
      to 1.69 +/- 1.61 arbitrary units P < 0.05). Additionally, the LDL-r mRNA
      abundance was decreased in the EGG group (1.72 +/- 0.69 to 1.24 +/- 0.55
      arbitrary units P < 0.05) and significantly increased in the SUB group (1.00 +/-
      0.60 to 1.67 +/- 1.94 arbitrary units P < 0.05). The findings indicate that
      dietary cholesterol during a weight loss intervention alters the expression of
      genes regulating cholesterol homeostasis.

PMID- 18045476
TI  - Effects of arachidonic acid supplementation on training adaptations in resistance
      trained males.
AB  - BACKGROUND: To determine the impact of AA supplementation during resistance
      training on body composition, training adaptations, and markers of muscle
      hypertrophy in resistance-trained males. METHODS: In a randomized and double
      blind manner, 31 resistance-trained male subjects (22.1 +/- 5.0 years, 180 +/-
      0.1 cm, 86.1 +/- 13.0 kg, 18.1 +/- 6.4% body fat) ingested either a placebo (PLA:
      1 g.day-1 corn oil, n = 16) or AA (AA: 1 g.day-1 AA, n = 15) while participating
      in a standardized 4 day.week-1 resistance training regimen. Fasting blood
      samples, body composition, bench press one-repetition maximum (1RM), leg press
      1RM and Wingate anaerobic capacity sprint tests were completed after 0, 25, and
      50 days of supplementation. Percutaneous muscle biopsies were taken from the
      vastus lateralis on days 0 and 50. RESULTS: Wingate relative peak power was
      significantly greater after 50 days of supplementation while the inflammatory
      cytokine IL-6 was significantly lower after 25 days of supplementation in the AA
      group. PGE2 levels tended to be greater in the AA group. However, no
      statistically significant differences were observed between groups in body
      composition, strength, anabolic and catabolic hormones, or markers of muscle
      hypertrophy (i.e. total protein content or MHC type I, IIa, and IIx protein
      content) and other intramuscular markers (i.e. FP and EP3 receptor density or MHC
      type I, IIa, and IIx mRNA expression). CONCLUSION: AA supplementation during
      resistance-training may enhance anaerobic capacity and lessen the inflammatory
      response to training. However, AA supplementation did not promote statistically
      greater gains in strength, muscle mass, or influence markers of muscle
      hypertrophy.

PMID- 18045477
TI  - Cooperative learning in the first year of undergraduate medical education.
AB  - BACKGROUND: Despite extensive research data indicating that cooperative learning
      promotes higher achievement, the creation of positive relationships, and greater
      psychological health for students at all levels in their education, cooperative
      learning as a teaching strategy is still underutilized in undergraduate medical
      education. METHODS: A cooperative learning task was introduced as part of the
      mandatory first Year undergraduate Pathology course. The task was to create an
      8.5" x 11" poster summary of pre-assigned content in self-chosen groups of four
      or five students. On the designated "Poster Day," the posters were displayed and
      evaluated by the students using a group product evaluation. Students also
      completed an individual group process reflection survey. An objective evaluation
      of their understanding was gauged at the midterm examination by specific content
      related questions. RESULTS: Majority (91-96%) of students judged the group
      products to be relevant, effective, easy-to-understand, and clearly communicated.
      The majority of the students (90-100%) agreed that their group process skills of
      time management, task collaboration, decision-making and task execution were
      effective in completing this exercise. This activity created a dynamic learning
      environment as was reflected in the students' positive, professional discussion,
      and evaluation of their posters. The content-related questions on the midterm
      examination were answered correctly by 70-92% of the students. This was a
      mutually enriching experience for the instructor and students. CONCLUSION: These
      findings demonstrate that cooperative learning as a teaching strategy can be
      effectively incorporated to address both content and interpersonal skill
      development in the early years of undergraduate medical education.

PMID- 18045478
TI  - Gene expression profiling of leukemic cells and primary thymocytes predicts a
      signature for apoptotic sensitivity to glucocorticoids.
AB  - BACKGROUND: Glucocorticoids (GC's) play an integral role in treatment strategies
      designed to combat various forms of hematological malignancies. GCs also are
      powerful inhibitors of the immune system, through regulation of appropriate
      cytokines and by causing apoptosis of immature thymocytes. By activating the
      glucocorticoid receptor (GR), GCs evoke apoptosis through transcriptional
      regulation of a complex, interactive gene network over a period of time preceding
      activation of the apoptotic enzymes. In this study we used microarray technology
      to determine whether several disparate types of hematologic cells, all sensitive
      to GC-evoked apoptosis, would identify a common set of regulated genes. We
      compared gene expression signatures after treatment with two potent synthetic
      GCs, dexamethasone (Dex) and cortivazol (CVZ) using a panel of hematologic cells.
      Pediatric CD4+/CD8+ T-cell leukemia was represented by 3 CEM clones: two
      sensitive, CEM-C7-14 and CEM-C1-6, and one resistant, CEM-C1-15, to Dex. CEM-C1
      15 was also tested when rendered GC-sensitive by several treatments. GC-sensitive
      pediatric B-cell leukemia was represented by the SUP-B15 line and adult B-cell
      leukemia by RS4;11 cells. Kasumi-1 cells gave an example of the rare Dex
      sensitive acute myeloblastic leukemia (AML). To test the generality of the
      correlations in malignant cell gene sets, we compared with GC effects on mouse
      non-transformed thymocytes. RESULTS: We identified a set of genes regulated by
      GCs in all GC-sensitive malignant cells. A portion of these were also regulated
      in the thymocytes. Because we knew that the highly Dex-resistant CEM-C1-15 cells
      could be killed by CVZ, we tested these cells with the latter steroid and again
      found that many of the same genes were now regulated as in the inherently GC
      sensitive cells. The same result was obtained when we converted the Dex-resistant
      clone to Dex-sensitive by treatment with forskolin (FSK), to activate the adenyl
      cyclase/protein kinase A pathway (PKA). CONCLUSION: Our results have identified
      small sets of genes that correlate with GC-sensitivity in cells from several
      hematologic malignancies. Some of these are also regulated in normal mouse
      thymocytes.

PMID- 18045480
TI  - Seek first to understand.
AB  - A recent study suggests that doctors often diminish effective time with patients
      by talking about themselves in a manner that does not improve the patient visit
      and is sometimes disruptive to it. Good care requires hearing what the patient
      has to say, as the doctor cannot set proper goals for a visit without knowing the
      patient's agenda. Listening to the patient is the key both to good patient care
      and to caring for the patient.

PMID- 18045479
TI  - Dynamic and redundant regulation of LRRK2 and LRRK1 expression.
AB  - BACKGROUND: Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene
      account for a significant proportion of autosomal-dominant and some late-onset
      sporadic Parkinson's disease. Elucidation of LRRK2 protein function in health and
      disease provides an opportunity for deciphering molecular pathways important in
      neurodegeneration. In mammals, LRRK1 and LRRK2 protein comprise a unique family
      encoding a GTPase domain that controls intrinsic kinase activity. The expression
      profiles of the murine LRRK proteins have not been fully described and
      insufficiently characterized antibodies have produced conflicting results in the
      literature. RESULTS: Herein, we comprehensively evaluate twenty-one commercially
      available antibodies to the LRRK2 protein using mouse LRRK2 and human LRRK2
      expression vectors, wild-type and LRRK2-null mouse brain lysates and human brain
      lysates. Eleven antibodies detect over-expressed human LRRK2 while four
      antibodies detect endogenous human LRRK2. In contrast, two antibodies recognize
      over-expressed mouse LRRK2 and one antibody detected endogenous mouse LRRK2.
      LRRK2 protein resides in both soluble and detergent soluble protein fractions.
      LRRK2 and the related LRRK1 genes encode low levels of expressed mRNA species
      corresponding to low levels of protein both during development and in adulthood
      with largely redundant expression profiles. CONCLUSION: Despite previously
      published results, commercially available antibodies generally fail to recognize
      endogenous mouse LRRK2 protein; however, several antibodies retain the ability to
      detect over-expressed mouse LRRK2 protein. Over half of the commercially
      available antibodies tested detect over-expressed human LRRK2 protein and some
      have sufficient specificity to detect endogenous LRRK2 in human brain. The
      mammalian LRRK proteins are developmentally regulated in several tissues and
      coordinated expression suggest possible redundancy in the function between LRRK1
      and LRRK2.

PMID- 18045481
TI  - Loss of international medical experiences: knowledge, attitudes and skills at
      risk.
AB  - BACKGROUND: Despite the great influence International Medical Experiences (IMs)
      can have on young physicians and their impact on patients and communities, they
      are not offered in all training programs and are at risk of being reduced in some
      due to stringent guidelines for funding of graduate medical education.
      DISCUSSION: IMs provide unique experiences in clinical, epidemiologic, cultural,
      and political arenas. From an educational perspective, they broaden a physician's
      differential diagnostic skills and introduce clinical entities rarely seen in the
      U.S. Time spent in developing countries emphasizes the importance of community
      health and increases cultural and linguistic competence. Experience working with
      the underserved during an IM has been shown to increase interest in volunteerism,
      humanitarian efforts, and work with underserved populations both in the US and
      abroad. IMs also afford physicians the opportunity to learn about the delivery of
      health care abroad and are associated with an increase in primary care specialty
      choice. SUMMARY: It is time for the leaders in graduate medical education to
      prioritize international health opportunities. Leaders in academic medicine can
      press for changes in reimbursement patterns at the national level or special
      funds for international electives. Hospitals can set up separate accounts to help
      finance resident salaries and benefits while abroad. Individual departments must
      be flexible with resident schedules to allow elective time. Medical students and
      housestaff can organize and lobby larger organizations such as the American
      Medical Association (AMA), the American Association of Medical Colleges (AAMC),
      and specialty groups to make IMs universally accessible.

PMID- 18045482
TI  - Effects of insurance status on children's access to specialty care: a systematic
      review of the literature.
AB  - BACKGROUND: The current climate of rising health care costs has led many health
      insurance programs to limit benefits, which may be problematic for children
      needing specialty care. Findings from pediatric primary care may not transfer to
      pediatric specialty care because pediatric specialists are often located in
      academic medical centers where institutional rules determine accepted insurance.
      Furthermore, coverage for pediatric specialty care may vary more widely due to
      systematic differences in inclusion on preferred provider lists, lack of
      availability in staff model HMOs, and requirements for referral. Our objective
      was to review the literature on the effects of insurance status on children's
      access to specialty care. METHODS: We conducted a systematic review of original
      research published between January 1, 1992 and July 31, 2006. Searches were
      performed using Pubmed. RESULTS: Of 30 articles identified, the majority use
      number of specialty visits or referrals to measure access. Uninsured children
      have poorer access to specialty care than insured children. Children with public
      coverage have better access to specialty care than uninsured children, but poorer
      access compared to privately insured children. Findings on the effects of managed
      care are mixed. CONCLUSION: Insurance coverage is clearly an important factor in
      children's access to specialty care. However, we cannot determine the structure
      of insurance that leads to the best use of appropriate, quality care by children.
      Research about specific characteristics of health plans and effects on health
      outcomes is needed to determine a structure of insurance coverage that provides
      optimal access to specialty care for children.

PMID- 18045483
TI  - LysoPC acyltransferase/PC transacylase activities in plant plasma membrane and
      plasma membrane-associated endoplasmic reticulum.
AB  - BACKGROUND: The phospholipids of the plant plasma membrane are synthesized in the
      endoplasmic reticulum (ER). The majority of these lipids reach the plasma
      membrane independently of the secretory vesicular pathway. Phospholipid delivery
      to the mitochondria and chloroplasts of plant cells also bypasses the secretory
      pathway and here it has been proposed that lysophospholipids are transported at
      contact sites between specific regions of the ER and the respective organelle,
      followed by lysophospholipid acylation in the target organelle. To test the
      hypothesis that a corresponding mechanism operates to transport phospholipids to
      the plasma membrane outside the secretory pathway, we investigated whether
      lysolipid acylation occurs also in the plant plasma membrane and whether this
      membrane, like the chloroplasts and mitochondria, is in close contact with the
      ER. RESULTS: The plant plasma membrane readily incorporated the acyl chain of
      acyl-CoA into phospholipids. Oleic acid was preferred over palmitic acid as
      substrate and acyl incorporation occurred predominantly into phosphatidylcholine
      (PC). Phospholipase A2 stimulated the reaction, as did exogenous lysoPC when
      administered in above critical micellar concentrations. AgNO3 was inhibitory. The
      lysophospholipid acylation reaction was higher in a membrane fraction that could
      be washed off the isolated plasma membranes after repeated freezing and thawing
      cycles in a medium with lowered pH. This fraction exhibited several ER-like
      characteristics. When plasma membranes isolated from transgenic Arabidopsis
      expressing green fluorescent protein in the ER lumen were observed by confocal
      microscopy, membranes of ER origin were associated with the isolated plasma
      membranes. CONCLUSION: We conclude that a lysoPC acylation activity is associated
      with plant plasma membranes and cannot exclude a PC transacylase activity. It is
      highly plausible that the enzyme(s) resides in a fraction of the ER, closely
      associated with the plasma membrane, or in both. We suggest that this fraction
      might be the equivalent of the mitochondria associated membrane of ER origin that
      delivers phospholipids to the mitochondria, and to the recently isolated ER
      derived membrane fraction that is in close contact with chloroplasts. The in situ
      function of the lysoPC acylation/PC transacylase activity is unknown, but
      involvement in lipid delivery from the ER to the plasma membrane is suggested.

PMID- 18045484
TI  - The invariant phenylalanine of precursor proteins discloses the importance of
      Omp85 for protein translocation into cyanelles.
AB  - BACKGROUND: Today it is widely accepted that plastids are of cyanobacterial
      origin. During their evolutionary integration into the metabolic and regulatory
      networks of the host cell the engulfed cyanobacteria lost their independency.
      This process was paralleled by a massive gene transfer from symbiont to the host
      nucleus challenging the development of a retrograde protein translocation system
      to ensure plastid functionality. Such a system includes specific targeting
      signals of the proteins needed for the function of the plastid and membrane-bound
      machineries performing the transfer of these proteins across the envelope
      membranes. At present, most information on protein translocation is obtained by
      the analysis of land plants. However, the analysis of protein import into the
      primitive plastids of glaucocystophyte algae, revealed distinct features placing
      this system as a tool to understand the evolutionary development of translocation
      systems. Here, bacterial outer membrane proteins of the Omp85 family have
      recently been discussed as evolutionary seeds for the development of
      translocation systems. RESULTS: To further explore the initial mode of protein
      translocation, the observed phenylalanine dependence for protein translocation
      into glaucophyte plastids was pursued in detail. We document that indeed the
      phenylalanine has an impact on both, lipid binding and binding to proteoliposomes
      hosting an Omp85 homologue. Comparison to established import experiments,
      however, unveiled a major importance of the phenylalanine for recognition by
      Omp85. This finding is placed into the context of the evolutionary development of
      the plastid translocon. CONCLUSION: The phenylalanine in the N-terminal domain
      signs as a prerequisite for protein translocation across the outer membrane
      assisted by a "primitive" translocon. This amino acid appears to be optimized for
      specifically targeting the Omp85 protein without enforcing aggregation on the
      membrane surface. The phenylalanine has subsequently been lost in the transit
      sequence, but can be found at the C-terminal position of the translocating pore.
      Thereby, the current hypothesis of Omp85 being the prokaryotic contribution to
      the ancestral Toc translocon can be supported.

PMID- 18045486
TI  - Ocular pathology of uncommon hematologic malignancies: a case series.
AB  - INTRODUCTION: In general, ocular complications of hematologic malignancies such
      as leukemia are well documented. However, reports of ocular involvement in such
      diseases as lymphomatoid granulomatosis and chronic myelomonocytic leukemia are
      uncommon. Here we present cases of these two relatively rare hematologic
      malignancies demonstrating clinical and subclinical ocular involvement. CASE
      PRESENTATION: In the first case, a 54-year-old man with a previous diagnosis of
      lymphomatoid granulomatosis presented with a new-onset conjunctival lesion while
      his systemic disease was thought to be in remission. A biopsy was taken that
      revealed heavy infiltrates of B and T cells at the site of the lesion. Molecular
      analysis confirmed that these cells were positive for both Epstein-Barr viral DNA
      and immunoglobulin heavy chain gene rearrangement, consistent with a
      manifestation of his systemic disease. In the second case, a 51-year-old man with
      chronic myelomonocytic leukemia died after a waxing and waning clinical course.
      Post-mortem studies revealed the presence of atypical monocytes in the choroidal
      and subretinal spaces, consistent with his previous diagnosis. CONCLUSION: While
      ocular involvement in hematologic malignancies is not uncommon, these two cases
      describe involvement of the eye by two relatively rare neoplasms. We herein
      emphasize novel findings in each case, including conjunctival involvement as the
      first sign of recurrent lymphomatoid granulomatosis and the combination of
      subretinal and choroidal myelomonocytic leukemic infiltration. With the evolution
      of new antineoplastic therapies that may prolong life, these cases exemplify the
      importance of eye care in patients diagnosed with hematologic malignancies.

PMID- 18045485
TI  - The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from
      having effects in type 1 diabetes.
AB  - BACKGROUND: As genes associated with immune-mediated diseases have an increased
      prior probability of being associated with other immune-mediated diseases, we
      tested three such genes, IL23R, IRF5 and CD40, for an association with type 1
      diabetes. In addition, we tested seven genes, TAF5L, PDCD1, TCF7, IL12B, IL6,
      ICAM1 and TBX21, with published marginal or inconsistent evidence of an
      association with type 1 diabetes. METHODS: We genotyped reported polymorphisms of
      the ten genes, nonsynonymous SNPs (nsSNPs) and, for the IL12B and IL6 regions,
      tag SNPs in up to 7,888 case, 8,858 control and 3,142 parent-child trio samples.
      In addition, we analysed data from the Wellcome Trust Case Control Consortium
      genome-wide association study to determine whether there was any further evidence
      of an association in each gene region. RESULTS: We found some evidence of
      associations between type 1 diabetes and TAF5L, PDCD1, TCF7 and IL6 (ORs = 1.05 -
      1.13; P = 0.0291 - 4.16 x 10-4). No evidence of an association was obtained for
      IL12B, IRF5, IL23R, ICAM1, TBX21 and CD40, although there was some evidence of an
      association (OR = 1.10; P = 0.0257) from the genome-wide association study for
      the ICAM1 region. CONCLUSION: We failed to exclude the possibility of some effect
      in type 1 diabetes for TAF5L, PDCD1, TCF7, IL6 and ICAM1. Additional studies, of
      these and other candidate genes, employing much larger sample sizes and analysis
      of additional polymorphisms in each gene and its flanking region will be required
      to ascertain their contributions to type 1 diabetes susceptibility.

PMID- 18045487
TI  - Identifying the determinants of premature mortality in Russia: overcoming a
      methodological challenge.
AB  - BACKGROUND: It is thought that excessive alcohol consumption is related to the
      high mortality among working age men in Russia. Moreover it has been suggested
      that alcohol is a key proximate driver of the very sharp fluctuations in
      mortality seen in this group since the mid-1980s. Designing an individual-level
      study suitable to address the potential acute effects of alcohol consumption on
      mortality in Russia has posed a challenge to epidemiologists, especially because
      of the need to identify factors that could underlie the rapid changes up and down
      in mortality rates that have been such a distinctive feature of the Russian
      mortality crisis. In order to address this study question which focuses on
      exposures acting shortly before sudden death, a cohort would be unfeasibly large
      and would suffer from recruitment bias. METHODS: Although the situation in Russia
      is unusual, with a very high death rate characterised by many sudden and
      apparently unexpected deaths in young men, the methodological problem is common
      to research on any cause of death where many deaths are sudden. RESULTS: We
      describe the development of an innovative approach that has overcome some of
      these challenges: a case-control study employing proxy informants and external
      data sources to collect information about proximate determinants of mortality.
      CONCLUSION: This offers a set of principles that can be adopted by
      epidemiologists studying sudden and unexpected deaths in other settings.

PMID- 18045488
TI  - Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic
      damage in rats with obstructive jaundice: an experimental study.
AB  - BACKGROUND: Peroxisome proliferators-activated receptor alpha (PPARalpha)
      activation modulates cholesterol metabolism and suppresses bile acid synthesis.
      This study aims to evaluate the effect of short-term administration of
      fenofibrate, a PPARalpha agonist, on proinflammatory cytokines, apoptosis, and
      hepatocellular damage in cholestasis. METHODS: Forty male Wistar rats were
      randomly divided into four groups: I = sham operated, II = bile duct ligation
      (BDL), III = BDL + vehicle (gum Arabic), IV = BDL + fenofibrate (100 mg/kg/day).
      All rats were sacrificed on 7th day after obtaining blood samples and liver
      tissue. Total bilirubin, aminotransferase (AST), alanine aminotransferase (ALT)
      and alkaline phosphatase (ALP), gamma-glutamyl transferase, (GGT), tumor necrosis
      factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and total bile acid
      (TBA) in serum, and liver damage scores; portal inflammation, necrosis, bile duct
      number, in liver tissue were evaluated. Apoptosis in liver was also assessed by
      immunohistochemical staining. RESULTS: Fenofibrate administration significantly
      reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-alpha, IL-1 beta
      levels, and TBA (P < 0.01). Hepatic portal inflammation, hepatic necrosis, number
      of the bile ducts and apoptosis in rats with BDL were more prominent than the
      sham-operated animals (P < 0.01). PPARalpha induction improved all
      histopathologic parameters (P < 0.01), except for the number of the bile duct,
      which was markedly increased by fenofibrate therapy (P < 0.01). CONCLUSION: Short
      term administration of fenofibrate to the BDL rats exerts beneficial effects on
      hepatocellular damage and apoptosis.

PMID- 18045490
TI  - Foundation doctors in anaesthesia: should they be taught to administer an
      anaesthetic?
AB  - BACKGROUND: Anaesthetic pre-registration house officer posts have been available
      since 1997. With the change to postgraduate medical training introduced in 2005,
      these posts have become vital building blocks for Foundation Programmes.
      DISCUSSION: We debate the skills that new Foundation Programme doctors in such
      posts should be taught, particularly whether administration of an anaesthetic
      holds an important place. The opinion of college tutors prior to the institution
      of the foundation programme is included. These were obtained from a postal
      questionnaire. SUMMARY: We maintain that teaching how to administer an
      anaesthetic remains an important learning objective and something that should be
      actively pursued.

PMID- 18045489
TI  - Genome-wide changes in expression profile of murine endogenous retroviruses
      (MuERVs) in distant organs after burn injury.
AB  - BACKGROUND: Previous studies have shown that burn-elicited stress signals alter
      expression of certain murine endogenous retroviruses (MuERVs) in distant organs
      of mice. These findings suggest that MuERVs may participate in a network of
      pathophysiologic events during post-burn systemic response. To gain a better
      understanding of the biological roles of MuERVs in post-burn systemic response,
      we examined the genome-wide changes in the MuERV expression profiles in distant
      organs and the biological properties of the putative-burn related MuERVs were
      characterized. RESULTS: Female C57BL/6J mice were subjected to an approximately
      18 % total body surface area flame burn and tissues (liver, lung, and kidney)
      were harvested at 3 hours and 24 hours after injury. The changes in the MuERV
      expression profiles in these tissues were examined by RT-PCR using a primer set
      flanking the non-ecotropic MuERV U3 promoter region within the 3' long terminal
      repeat. There were differential changes in the expression profiles of MuERV U3
      regions after injury in all three tissues examined. Subsequently, a total of 31
      unique U3 promoter sequences were identified from the tissues of both burn and no
      burn mice. An analysis of viral tropisms revealed that putative MuERVs harboring
      these U3 promoter sequences were presumed to be either xenotropic or polytropic.
      Some putative transcription regulatory elements were present predominantly in U3
      promoter sequences isolated from burn and no burn mice, respectively. In
      addition, in silico mapping using these U3 sequences as a probe against the mouse
      genome database identified 59 putative MuERVs. The biological properties (coding
      potentials for retroviral polypeptides, primer binding sites, tropisms, branching
      ages, recombination events, and neighboring host genes) of each putative MuERV
      were characterized. In particular, 16 putative MuERVs identified in this study
      retained intact coding potentials for all three retroviral polypeptides (gag,
      pol, and env). None of the putative MuERVs identified in this study were mapped
      to the coding sequences of host genes. CONCLUSION: In this study, we identified
      and characterized putative MuERVs whose expression might be altered in response
      to burn-elicited systemic stress signals. Further investigation is needed to
      understand the role of these MuERVs in post-burn systemic pathogenesis, in
      particular, via characterization of their interaction with host genes, MuERV gene
      products, and viral activities.

PMID- 18045491
TI  - Predicting RNA secondary structure by the comparative approach: how to select the
      homologous sequences.
AB  - BACKGROUND: The secondary structure of an RNA must be known before the
      relationship between its structure and function can be determined. One way to
      predict the secondary structure of an RNA is to identify covarying residues that
      maintain the pairings (Watson-Crick, Wobble and non-canonical pairings). This
      "comparative approach" consists of identifying mutations from homologous sequence
      alignments. The sequences must covary enough for compensatory mutations to be
      revealed, but comparison is difficult if they are too different. Thus the choice
      of homologous sequences is critical. While many possible combinations of
      homologous sequences may be used for prediction, only a few will give good
      structure predictions. This can be due to poor quality alignment in stems or to
      the variability of certain sequences. This problem of sequence selection is
      currently unsolved. RESULTS: This paper describes an algorithm, SSCA, which
      measures the suitability of sequences for the comparative approach. It is based
      on evolutionary models with structure constraints, particularly those on sequence
      variations and stem alignment. We propose three models, based on different
      constraints on sequence alignments. We show the results of the SSCA algorithm for
      predicting the secondary structure of several RNAs. SSCA enabled us to choose
      sets of homologous sequences that gave better predictions than arbitrarily chosen
      sets of homologous sequences. CONCLUSION: SSCA is an algorithm for selecting
      combinations of RNA homologous sequences suitable for secondary structure
      predictions with the comparative approach.

PMID- 18045492
TI  - Cerebral haemodynamics and carbon dioxide reactivity during sepsis syndrome.
AB  - BACKGROUND: Most patients with sepsis develop potentially irreversible cerebral
      dysfunctions. It is yet not clear whether cerebral haemodynamics are altered in
      these sepsis patients at all, and to what extent. We hypothesized that cerebral
      haemodynamics and carbon dioxide reactivity would be impaired in patients with
      sepsis syndrome and pathological electroencephalogram patterns. METHODS: After
      approval of the institutional ethics committee, 10 mechanically ventilated
      patients with sepsis syndrome and pathological electroencephalogram patterns
      underwent measurements of cerebral blood flow and jugular venous oxygen
      saturation before and after reduction of the arterial carbon dioxide partial
      pressure by 0.93 +/- 0.7 kPa iu by hyperventilation. The cerebral capillary
      closing pressure was determined from transcranial Doppler measurements of the
      arterial blood flow of the middle cerebral artery and the arterial pressure
      curve. A t test for matched pairs was used for statistical analysis (P < 0.05).
      RESULTS: During stable mean arterial pressure and cardiac index, reduction of the
      arterial carbon dioxide partial pressure led to a significant increase of the
      capillary closing pressure from 25 +/- 11 mmHg to 39 +/- 15 mmHg (P < 0.001),
      with a consecutive decrease of blood flow velocity in the middle cerebral artery
      of 21.8 +/- 4.8%/kPa (P < 0.001), of cerebral blood flow from 64 +/- 29 ml/100
      g/min to 39 +/- 15 ml/100 g/min (P < 0.001) and of jugular venous oxygen
      saturation from 75 +/- 8% to 67 +/- 14% (P < 0.01). CONCLUSION: In contrast to
      other experimental and clinical data, we observed no pathological findings in the
      investigated parameters of cerebral perfusion and oxygenation.

PMID- 18045493
TI  - Effects of body position on autonomic regulation of cardiovascular function in
      young, healthy adults.
AB  - BACKGROUND: Analysis of rhythmic patterns embedded within beat-to-beat variations
      in heart rate (heart rate variability) is a tool used to assess the balance of
      cardiac autonomic nervous activity and may be predictive for prognosis of some
      medical conditions, such as myocardial infarction. It has also been used to
      evaluate the impact of manipulative therapeutics and body position on autonomic
      regulation of the cardiovascular system. However, few have compared cardiac
      autonomic activity in supine and prone positions, postures commonly assumed by
      patients in manual therapy. We intend to redress this deficiency. METHODS: Heart
      rate, heart rate variability, and beat-to-beat blood pressure were measured in
      young, healthy non-smokers, during prone, supine, and sitting postures and with
      breathing paced at 0.25 Hz. Data were recorded for 5 minutes in each posture: Day
      1 - prone and supine; Day 2 - prone and sitting. Paired t-tests or Wilcoxon
      signed-rank tests were used to evaluate posture-related differences in blood
      pressure, heart rate, and heart rate variability. RESULTS: Prone versus supine:
      blood pressure and heart rate were significantly higher in the prone posture (p <
      0.001). Prone versus sitting: blood pressure was higher and heart rate was lower
      in the prone posture (p < 0.05) and significant differences were found in some
      components of heart rate variability. CONCLUSION: Cardiac autonomic activity was
      not measurably different in prone and supine postures, but heart rate and blood
      pressure were. Although heart rate variability parameters indicated sympathetic
      dominance during sitting (supporting work of others), blood pressure was higher
      in the prone posture. These differences should be considered when autonomic
      regulation of cardiovascular function is studied in different postures.

PMID- 18045494
TI  - Interspecies and intraspecies transmission of triple reassortant H3N2 influenza A
      viruses.
AB  - The triple reassortant H3N2 viruses were isolated for the first time from pigs in
      1998 and are known to be endemic in swine and turkey populations in the United
      States. In 2004, we isolated two H3N2 triple reassortant viruses from two turkey
      breeder flocks in Ohio and Illinois. Infected hens showed no clinical signs, but
      experienced a complete cessation of egg production. In this study, we evaluated
      three triple reassortant H3N2 isolates of turkey origin and one isolate of swine
      origin for their transmission between swine and turkeys. Although all 4 viruses
      tested share high genetic similarity in all 8 genes, only the Ohio strain
      (A/turkey/Ohio/313053/04) was shown to transmit efficiently both ways between
      swine and turkeys. One isolate, A/turkey/North Carolina/03, was able to transmit
      from pigs to turkeys but not vice versa. Neither of the other two viruses
      transmitted either way. Sequence analysis of the HA1 gene of the Ohio strain
      showed one amino acid change (D to A) at residue 190 of the receptor binding
      domain upon transmission from turkeys to pigs. The Ohio virus was then tested for
      intraspecies transmission in three different avian species. The virus was shown
      to replicate and transmit among turkeys, replicate but does not transmit among
      chickens, and did not replicate in ducks. Identifying viruses with varying inter-
      and intra-species transmission potential should be useful for further studies on
      the molecular basis of interspecies transmission.

PMID- 18045495
TI  - Effect of electronic patient record use on mortality in End Stage Renal Disease,
      a model chronic disease: retrospective analysis of 9 years of prospectively
      collected data.
AB  - BACKGROUND: In chronic disease, health information technology promises but has
      yet to demonstrate improved outcomes and decreased costs. The main aim of the
      study was to determine the effects on mortality and cost of an electronic patient
      record used in daily patient care in a model chronic disease, End Stage Renal
      Disease, treated by chronic maintenance hemodialysis. Dialysis treatment is
      highly regulated, and near uniform in treatment modalities and drugs used.
      METHODS: The particular electronic patient record, patient-centered and
      extensively coded, was used first in patient care in 3 dialysis units in New
      York, NY in 1998, 1999, and 2000. All data were stored "live"; none were
      archived. By December 31, 2006, the patients had been treated by maintenance
      hemodialysis for a total of 3924 years. A retrospective analysis was made using
      query tools embedded in the software. The United States Renal Data System
      dialysis population served as controls. In all there were 1790 patients, with
      many underlying primary diseases and multiple comorbid conditions affecting many
      organ systems. Year by year mortality, hospital admissions, and staffing were
      analyzed, and the data were compared with national data compiled by the United
      States Renal Data System. RESULTS: Analyzed by calendar year after electronic
      patient record implementation, mortality decreased strikingly. In years 3-9
      mortality was lower than in years 1-2 by 23%, 48%, and 34% in the 3 units, and
      was 37%, 37%, and 35% less than that reported by the United States Renal Data
      System. Clinical staffing was 25% fewer per 100 patients than the national
      average, thereby lowering costs. CONCLUSION: To our knowledge, this is the first
      demonstration that an electronic patient record, albeit of particular design, can
      have a favorable effect on outcomes and cost in chronic disease. That the
      population studied has many underlying diseases affecting all organ systems
      suggests that the electronic patient record design may enable application to many
      fields of medical practice.

PMID- 18045496
TI  - HCCR-1, a novel oncogene, encodes a mitochondrial outer membrane protein and
      suppresses the UVC-induced apoptosis.
AB  - BACKGROUND: The Human cervical cancer oncogene (HCCR-1) has been isolated as a
      human oncoprotein, and has shown strong tumorigenic features. Its potential role
      in tumorigenesis may result from a negative regulation of the p53 tumor
      suppressor gene. RESULTS: To investigate the biological function of HCCR-1 in the
      cell, we predicted biological features using bioinformatic tools, and have
      identified a LETM1 homologous domain at position 75 to 346 of HCCR-1. This domain
      contains proteins identified from diverse species predicted to be mitochondrial
      proteins. Fluorescence microscopy and fractionation experiments showed that HCCR
      1 is located in mitochondria in the COS-7, MCF-7 and HEK/293 cell lines, and
      subcompartamentally at the outer membrane in the HEK/293 cell line. The
      topological structure was revealed as the NH2-terminus of HCCR-1 oriented toward
      the cytoplasm. We also observed that the D1-2 region, at position 1 to 110 of
      HCCR-1, was required and sufficient for posttranslational mitochondrial import.
      The function of HCCR-1 on mitochondrial membrane is to retard the intrinsic
      apoptosis induced by UVC and staurosporine, respectively. CONCLUSION: Our
      experiments show the biological features of HCCR-1 in the cell, and suggest that
      uncontrolled expression of HCCR-1 may cause mitochondrial dysfunction that can
      result in resisting the UVC or staurosporine-induced apoptosis and progressing in
      the tumor formation.

PMID- 18045497
TI  - Cadherin-mediated adhesion regulates posterior body formation.
AB  - BACKGROUND: The anterior-posterior axis of the vertebrate embryo undergoes a
      dramatic elongation during early development. Convergence and extension of the
      mesoderm, occurring during gastrulation, initiates the narrowing and lengthening
      of the embryo. However the lengthening of the axis continues during post-gastrula
      stages in the tailbud region, and is thought to involve convergent extension
      movements as well as other cell behaviors specific to posterior regions. RESULTS:
      We demonstrate here, using a semi-dominant N-cadherin allele, that members of the
      classical cadherin subfamily of cell-cell adhesion molecules are required for
      tailbud elongation in the zebrafish. In vivo imaging of cell behaviors suggests
      that the extension of posterior axial mesodermal cells is impaired in embryos
      that carry the semi-dominant N-cadherin allele. This defect most likely results
      from a general loss of cell-cell adhesion in the tailbud region. Consistent with
      these observations, N-cadherin is expressed throughout the tailbud during post
      gastrulation stages. In addition, we show that N-cadherin interacts
      synergistically with vang-like 2, a member of the non-canonical Wnt
      signaling/planar cell polarity pathway, to mediate tail morphogenesis.
      CONCLUSION: We provide the first evidence here that N-cadherin and other members
      of the classical cadherin subfamily function in parallel with the planar cell
      polarity pathway to shape the posterior axis during post-gastrulation stages.
      These findings further highlight the central role that adhesion molecules play in
      the cellular rearrangements that drive morphogenesis in vertebrates and identify
      classical cadherins as major contributors to tail development.

PMID- 18045499
TI  - Malnutrition and the disproportional burden on the poor: the case of Ghana.
AB  - BACKGROUND: Malnutrition is a major public health and development concern in the
      developing world and in poor communities within these regions. Understanding the
      nature and determinants of socioeconomic inequality in malnutrition is essential
      in contemplating the health of populations in developing countries and in
      targeting resources appropriately to raise the health of the poor and most
      vulnerable groups. METHODS: This paper uses a concentration index to summarize
      inequality in children's height-for-age z-scores in Ghana across the entire
      socioeconomic distribution and decomposes this inequality into different
      contributing factors. Data is used from the Ghana 2003 Demographic and Health
      Survey. RESULTS: The results show that malnutrition is related to poverty,
      maternal education, health care and family planning and regional characteristics.
      Socioeconomic inequality in malnutrition is mainly associated with poverty,
      health care use and regional disparities. Although average malnutrition is higher
      using the new growth standards recently released by the World Health
      Organization, socioeconomic inequality and the associated factors are robust to
      the change of reference population. CONCLUSION: Child malnutrition in Ghana is a
      multisectoral problem. The factors associated with average malnutrition rates are
      not necessarily the same as those associated with socioeconomic inequality in
      malnutrition.

PMID- 18045498
TI  - Phylogenomics and signature proteins for the alpha proteobacteria and its main
      groups.
AB  - BACKGROUND: Alpha proteobacteria are one of the largest and most extensively
      studied groups within bacteria. However, for these bacteria as a whole and for
      all of its major subgroups (viz. Rhizobiales, Rhodobacterales, Rhodospirillales,
      Rickettsiales, Sphingomonadales and Caulobacterales), very few or no distinctive
      molecular or biochemical characteristics are known. RESULTS: We have carried out
      comprehensive phylogenomic analyses by means of Blastp and PSI-Blast searches on
      the open reading frames in the genomes of several alpha-proteobacteria (viz.
      Bradyrhizobium japonicum, Brucella suis, Caulobacter crescentus, Gluconobacter
      oxydans, Mesorhizobium loti, Nitrobacter winogradskyi, Novosphingobium
      aromaticivorans, Rhodobacter sphaeroides 2.4.1, Silicibacter sp. TM1040,
      Rhodospirillum rubrum and Wolbachia (Drosophila) endosymbiont). These studies
      have identified several proteins that are distinctive characteristics of all
      alpha-proteobacteria, as well as numerous proteins that are unique repertoires of
      all of its main orders (viz. Rhizobiales, Rhodobacterales, Rhodospirillales,
      Rickettsiales, Sphingomonadales and Caulobacterales) and many families (viz.
      Rickettsiaceae, Anaplasmataceae, Rhodospirillaceae, Acetobacteraceae,
      Bradyrhiozobiaceae, Brucellaceae and Bartonellaceae). Many other proteins that
      are present at different phylogenetic depths in alpha-proteobacteria provide
      important information regarding their evolution. The evolutionary relationships
      among alpha-proteobacteria as deduced from these studies are in excellent
      agreement with their branching pattern in the phylogenetic trees and character
      compatibility cliques based on concatenated sequences for many conserved
      proteins. These studies provide evidence that the major groups within alpha
      proteobacteria have diverged in the following order:
      (Rickettsiales(Rhodospirillales (Sphingomonadales (Rhodobacterales
      (Caulobacterales-Parvularculales (Rhizobiales)))))). We also describe two
      conserved inserts in DNA Gyrase B and RNA polymerase beta subunit that are
      distinctive characteristics of the Sphingomonadales and Rhodosprilllales species,
      respectively. The results presented here also provide support for the grouping of
      Hyphomonadaceae and Parvularcula species with the Caulobacterales and the
      placement of Stappia aggregata with the Rhizobiaceae group. CONCLUSION: The alpha
      proteobacteria-specific proteins and indels described here provide novel and
      powerful means for the taxonomic, biochemical and molecular biological studies on
      these bacteria. Their functional studies should prove helpful in identifying
      novel biochemical and physiological characteristics that are unique to these
      bacteria.

PMID- 18045500
TI  - Assessment of higher order cognitive skills in undergraduate education: modified
      essay or multiple choice questions? Research paper.
AB  - BACKGROUND: Reliable and valid written tests of higher cognitive function are
      difficult to produce, particularly for the assessment of clinical problem
      solving. Modified Essay Questions (MEQs) are often used to assess these higher
      order abilities in preference to other forms of assessment, including multiple
      choice questions (MCQs). MEQs often form a vital component of end-of-course
      assessments in higher education. It is not clear how effectively these questions
      assess higher order cognitive skills. This study was designed to assess the
      effectiveness of the MEQ to measure higher-order cognitive skills in an
      undergraduate institution. METHODS: An analysis of multiple-choice questions and
      modified essay questions (MEQs) used for summative assessment in a clinical
      undergraduate curriculum was undertaken. A total of 50 MCQs and 139 stages of
      MEQs were examined, which came from three exams run over two years. The
      effectiveness of the questions was determined by two assessors and was defined by
      the questions ability to measure higher cognitive skills, as determined by a
      modification of Bloom's taxonomy, and its quality as determined by the presence
      of item writing flaws. RESULTS: Over 50% of all of the MEQs tested factual
      recall. This was similar to the percentage of MCQs testing factual recall. The
      modified essay question failed in its role of consistently assessing higher
      cognitive skills whereas the MCQ frequently tested more than mere recall of
      knowledge. CONCLUSION: Construction of MEQs, which will assess higher order
      cognitive skills cannot be assumed to be a simple task. Well-constructed MCQs
      should be considered a satisfactory replacement for MEQs if the MEQs cannot be
      designed to adequately test higher order skills. Such MCQs are capable of
      withstanding the intellectual and statistical scrutiny imposed by a high stakes
      exit examination.

PMID- 18045501
TI  - Simulation of propofol anaesthesia for intracranial decompression using brain
      hypothermia treatment.
AB  - BACKGROUND: Although propofol is commonly used for general anaesthesia of
      normothermic patients in clinical practice, little information is available in
      the literature regarding the use of propofol anaesthesia for intracranial
      decompression using brain hypothermia treatment. A novel propofol anaesthesia
      scheme is proposed that should promote such clinical application and improve
      understanding of the principles of using propofol anaesthesia for hypothermic
      intracranial decompression. METHODS: Theoretical analysis was carried out using a
      previously-developed integrative model of the thermoregulatory, hemodynamic and
      pharmacokinetic subsystems. Propofol kinetics is described using a framework
      similar to that of this model and combined with the thermoregulation subsystem
      through the pharmacodynamic relationship between the blood propofol concentration
      and the thermoregulatory threshold. A propofol anaesthesia scheme for hypothermic
      intracranial decompression was simulated using the integrative model. RESULTS:
      Compared to the empirical anaesthesia scheme, the proposed anaesthesia scheme can
      reduce the required propofol dosage by more than 18%. CONCLUSION: The integrative
      model of the thermoregulatory, hemodynamic and pharmacokinetic subsystems is
      effective in analyzing the use of propofol anaesthesia for hypothermic
      intracranial decompression. This propofol infusion scheme appears to be more
      appropriate for clinical application than the empirical one.

PMID- 18045502
TI  - TFCONES: a database of vertebrate transcription factor-encoding genes and their
      associated conserved noncoding elements.
AB  - BACKGROUND: Transcription factors (TFs) regulate gene transcription and play
      pivotal roles in various biological processes such as development, cell cycle
      progression, cell differentiation and tumor suppression. Identifying cis
      regulatory elements associated with TF-encoding genes is a crucial step in
      understanding gene regulatory networks. To this end, we have used a comparative
      genomics approach to identify putative cis-regulatory elements associated with TF
      encoding genes in vertebrates. DESCRIPTION: We have created a database named
      TFCONES (Transcription Factor Genes & Associated COnserved Noncoding ElementS)
      (http://tfcones.fugu-sg.org) which contains all human, mouse and fugu TF-encoding
      genes and conserved noncoding elements (CNEs) associated with them. The CNEs were
      identified by gene-by-gene alignments of orthologous TF-encoding gene loci using
      MLAGAN. We also predicted putative transcription factor binding sites within the
      CNEs. A significant proportion of human-fugu CNEs contain experimentally defined
      binding sites for transcriptional activators and repressors, indicating that a
      majority of the CNEs may function as transcriptional regulatory elements. The TF
      encoding genes that are involved in nervous system development are generally
      enriched for human-fugu CNEs. Users can retrieve TF-encoding genes and their
      associated CNEs by conducting a keyword search or by selecting a family of DNA
      binding proteins. CONCLUSION: The conserved noncoding elements identified in
      TFCONES represent a catalog of highly prioritized putative cis-regulatory
      elements of TF-encoding genes and are candidates for functional assay.

PMID- 18045503
TI  - Evaluating the effect of neighbourhood weight matrices on smoothing properties of
      Conditional Autoregressive (CAR) models.
AB  - BACKGROUND: The Conditional Autoregressive (CAR) model is widely used in many
      small-area ecological studies to analyse outcomes measured at an areal level.
      There has been little evaluation of the influence of different neighbourhood
      weight matrix structures on the amount of smoothing performed by the CAR model.
      We examined this issue in detail. METHODS: We created several neighbourhood
      weight matrices and applied them to a large dataset of births and birth defects
      in New South Wales (NSW), Australia within 198 Statistical Local Areas. Between
      the years 1995-2003, there were 17,595 geocoded birth defects and 770,638
      geocoded birth records with available data. Spatio-temporal models were developed
      with data from 1995-2000 and their fit evaluated within the following time
      period: 2001-2003. RESULTS: We were able to create four adjacency-based weight
      matrices, seven distance-based weight matrices and one matrix based on similarity
      in terms of a key covariate (i.e. maternal age). In terms of agreement between
      observed and predicted relative risks, categorised in epidemiologically relevant
      groups, generally the distance-based matrices performed better than the adjacency
      based neighbourhoods. In terms of recovering the underlying risk structure, the
      weight-7 model (smoothing by maternal-age 'Covariate model') was able to
      correctly classify 35/47 high-risk areas (sensitivity 74%) with a specificity of
      47%, and the 'Gravity' model had sensitivity and specificity values of 74% and
      39% respectively. CONCLUSION: We found considerable differences in the smoothing
      properties of the CAR model, depending on the type of neighbours specified. This
      in turn had an effect on the models' ability to recover the observed risk in an
      area. Prior to risk mapping or ecological modelling, an exploratory analysis of
      the neighbourhood weight matrix to guide the choice of a suitable weight matrix
      is recommended. Alternatively, the weight matrix can be chosen a priori based on
      decision-theoretic considerations including loss, cost and inferential aims.

PMID- 18045504
TI  - Verification of the formulation and efficacy of Danggui Buxue Tang (a decoction
      of Radix Astragali and Radix Angelicae Sinensis): an exemplifying systematic
      approach to revealing the complexity of Chinese herbal medicine formulae.
AB  - This article exemplifies a systematic approach to revealing the complexity of
      Chinese herbal medicine formulae through three levels of scientific research:
      standardization of herbs, verification of ancient formulae and mechanism studies.
      We use Danggui Buxue Tang (DBT) as an example for this approach. Among thousands
      of traditional Chinese medicine herbal formulae, almost all of which consist of
      multiple herbs, DBT is one of the simplest. Containing only two herbs, namely
      Radix Astragali (RA) and Radix Angelicae Sinensis (RAS), DBT is traditionally
      used to treat ailments in women. The weight ratio of RA to RAS in DBT was
      prescribed to be 5:1 as early as in 1247 AD. In addition to advanced chemical
      analysis of herbal constituents, DNA genotyping techniques have been developed
      for reliable standardization of RA and RAS. Chemical evaluation shows that main
      active constituents in DBT, including astragaloside IV, calycosin, formononetin
      and ferulic acid, were most abundant after extraction at the RA to RAS ratio of
      5:1, whereas other tested RA to RAS ratios only gave sub-optimal levels of the
      active constituents. Biological evaluation indicates that bioactivities of DBT,
      e.g. immuno-modulatory, oesteotropic and estrogenic effects are also best exerted
      at the RA to RAS ratio of 5:1. Correlation analysis demonstrates statistically
      significant relationship between the tested chemical constituents and tested
      bioactivities. Up- and down-regulation of expression of some genes as potential
      biomarkers has been detected by using gene chip technology. This systematic
      approach on the basis of herbal standardization, chemical and biological
      verification and mechanism studies, as exemplified in this article, will be
      useful to reveal the complexity of not only DBT but also other Chinese medicine
      herbal formulae.

PMID- 18045505
TI  - Multiple host-switching of Haemosporidia parasites in bats.
AB  - BACKGROUND: There have been reported cases of host-switching in avian and lizard
      species of Plasmodium (Apicomplexa, Haemosporidia), as well as in those infecting
      different primate species. However, no evidence has previously been found for
      host-swapping between wild birds and mammals. METHODS: This paper presents the
      results of the sampling of blood parasites of wild-captured bats from Madagascar
      and Cambodia. The presence of Haemosporidia infection in these animals is
      confirmed and cytochrome b gene sequences were used to construct a phylogenetic
      analysis. RESULTS: Results reveal at least three different and independent
      Haemosporidia evolutionary histories in three different bat lineages from
      Madagascar and Cambodia. CONCLUSION: Phylogenetic analysis strongly suggests
      multiple host-switching of Haemosporidia parasites in bats with those from avian
      and primate hosts.

PMID- 18045506
TI  - A rare case of primary mesenteric gastrointestinal stromal tumor with metastasis
      to the cervix uteri.
AB  - BACKGROUND: Gastrointestinal stromal tumors are CD117 (C Kit) positive
      mesenchymal neoplasms, that may arise anywhere in the gastrointestinal tract.
      Their current therapy is imatinib mesylate before or after surgery. CASE
      PRESENTATION: We describe a case of 17-year-old female with metastasis to the
      cervix uteri of a primary mesenteric gastrointestinal tumor. CONCLUSION: Surgery
      remains the mainstay of known curative treatment. The manifestations of GIST are
      not restricted to the typical locations within the bowel; may have very unusual
      metastatic sites or infiltrations per continuitatem.

PMID- 18045507
TI  - Comparison of genomes of three Xanthomonas oryzae bacteriophages.
AB  - BACKGROUND: Xp10 and OP1 are phages of Xanthomonas oryzae pv. oryzae (Xoo), the
      causative agent of bacterial leaf blight in rice plants, which were isolated in
      1967 in Taiwan and in 1954 in Japan, respectively. We recently isolated the Xoo
      phage Xop411. RESULTS: The linear Xop411 genome (44,520 bp, 58 ORFs) sequenced
      here is 147 bp longer than that of Xp10 (60 ORFs) and 735 bp longer than that of
      OP1 (59 ORFs). The G+C contents of OP1 (51%) and Xop411 and Xp10 (52% each) are
      less than that of the host (65%). The 9-bp 3'-overhangs (5'-GGACAGTCT-3') in
      Xop411 and Xp10 are absent from OP1. More of the deduced Xop411 proteins share
      higher degrees of identity with Xp10 than with OP1 proteins, while the right end
      of the genomes of Xp10 and OP1, containing all predicted promoters, share
      stronger homology. Xop411, Xp10, and OP1 contain 8, 7, and 6 freestanding HNH
      endonuclease genes, respectively. These genes can be classified into five groups
      depending on their possession of the HNH domain (HNN or HNH type) and/or AP2
      domain in intact or truncated forms. While the HNN-AP2 type endonuclease genes
      dispersed in the genome, the HNH type endonuclease genes, each with a unique
      copy, were located within the same genome context. Mass spectrometry and N
      terminal sequencing showed nine Xop411 coat proteins, among which three were
      identified, six were assigned as coat proteins (4) and conserved phage proteins
      (2) in Xp10. The major coat protein, in which only the N-terminal methionine is
      removed, appears to exist in oligomeric forms containing 2 to 6 subunits. The
      three phages exhibit different patterns of domain duplication in the N-terminus
      of the tail fiber, which are involved in determination of the host range. Many
      short repeated sequences are present in and around the duplicated domains.
      CONCLUSION: Geographical separation may have confined lateral gene transfer among
      the Xoo phages. The HNN-AP2 type endonucleases were more likely to transfer their
      genes randomly in the genome and may degenerate after successful transmission.
      Some repeated sequences may be involved in duplication/loss of the domains in the
      tail fiber genes.

PMID- 18045508
TI  - An exploration of the use of simple statistics to measure consensus and stability
      in Delphi studies.
AB  - BACKGROUND: The criteria for stopping Delphi studies are often subjective. This
      study aimed to examine whether consensus and stability in the Delphi process can
      be ascertained by descriptive evaluation of trends in participants' views.
      METHODS: A three round email-based Delphi required participants (n = 12) to
      verify their level of agreement with 8 statements, write comments on each if they
      considered it necessary and rank the statements for importance. Each statement
      was analysed quantitatively by the percentage of agreement ratings, importance
      rankings and the amount of comments made for each statement, and qualitatively
      using thematic analysis. Importance rankings between rounds were compared by
      calculating Kappa values to observe trends in how the process impacts on
      subject's views. RESULTS: Evolution of consensus was shown by increase in
      agreement percentages, convergence of range with standard deviations of
      importance ratings, and a decrease in the number of comments made. Stability was
      demonstrated by a trend of increasing Kappa values. CONCLUSION: Following the
      original use of Delphi in social sciences, Delphi is suggested to be an effective
      way to gain and measure group consensus in healthcare. However, the proposed
      analytical process should be followed to ensure maximum validity of results in
      Delphi methodology for improved evidence of consensual decision-making.

PMID- 18045509
TI  - The influence of acculturation on breast-feeding initiation and duration in low
      income women in the US.
AB  - While the 'immigrant health paradox' posits better health behaviours and outcomes
      for immigrants upon arrival to the US, research suggests that this advantage may
      deteriorate over time. This study analysed the relationship of acculturation and
      breast-feeding initiation and duration among a sample of predominantly Latina,
      low-income women in the US. The four measures of acculturation included: mother's
      nativity (foreign born vs US born), mother's parents' nativity (foreign born vs
      US born), years of US residence (<8 years vs > or =8 years) and a dichotomous
      measure of language acculturation adapted from three items on Marin's
      acculturation scale (preferred language spoken at home, reading language and
      writing language) as exclusive use of native language versus non-exclusive use
      (mixed or English only) (Marin et al., 1987; Marin & Gamba, 1996). Final
      multivariable models showed that mothers who exclusively used their native
      language were more likely to initiate breast-feeding as well as breast-feed for
      longer duration compared with mothers with non-exclusive use, whereas years of US
      residence and mother's nativity were not significantly associated with breast
      feeding initiation or duration. Mother's parents' nativity also emerged as a
      significant predictor of breast-feeding duration, both within final models for
      immigrants and across study participants. Programmes providing nutrition
      education to low-income women may wish to consider the role of language as an
      important determinant of breast-feeding. The role of mother's parents' nativity
      on breast-feeding practices deserves exploration in future studies, as the
      cultural practices taught by family members born outside the US may exert strong
      pressure within immigrant families now living in the US.

PMID- 18045510
TI  - Pathogenesis of infantile haemangioma: new molecular and cellular insights.
AB  - Infantile haemangioma is the most common tumour of infancy, yet the origin of
      these lesions remains controversial and the predictable life cycle is poorly
      understood. Much new information on infantile haemangiomas has emerged over the
      past decade, but experts continue to debate fundamental features, including cell
      of origin, nonrandom distribution, and mechanisms regulating the sometimes
      explosive growth and slow involution. The development of useful laboratory models
      has been difficult, in turn restricting the development of treatment options
      available to the clinician. Despite this, new research and creative thinking has
      spawned several hypotheses on the origin of these tumours and their interesting
      clinical behaviour, including suggestions of an intrinsic defect in local
      endothelial cells, a contribution of circulating endothelial progenitors or
      haemangioblasts, embolisation of shed placental cells and developmental field
      defects. While no single hypothesis seems to describe all features of infantile
      haemangioma, continued research seeks to integrate these ideas, create a better
      understanding of these important tumours and bring new treatments to the clinic.

PMID- 18045511
TI  - Spinal cord injuries from road traffic crashes in southeastern Iran.
AB  - OBJECTIVE: To analyze the data of patients with spinal cord injury (SCI) induced
      by road traffic crashes in southeastern Iran for better understanding the pattern
      of these injuries and therefore for better designing health system planning.
      METHODS: In this historical cohort study, the patients who had been transferred
      to Level I trauma center in southeastern Iran due to road traffic accidents with
      radiographic documented SCI were evaluated. RESULTS: Among 64 patients with SCI,
      38 patients (59.4%, 36 males and 2 females, aged 27.42 years+/-9.44 years on
      average) were injured by road traffic accidents. Car and motorcycle accidents
      were responsible for 26 cases (68.4%) and 12 cases (31.6%), respectively. And 31
      patients (81.6%) had complete SCI. Conus medularis (T12-L2) was the most affected
      level. CONCLUSIONS: Results are discussed in terms of preventive measures,
      specifically those concerning the use of restraint and helmet and driving
      behavior. This study should be extended nationally to gain a larger case series
      so that the SCI risk of particular vehicle configurations, considering other
      crash factors, can be more precisely quantified and the characteristics for low
      occurrence of SCI can be more precisely identified.

PMID- 18045512
TI  - Biomechanical evaluation of vertebroplasty using calcium sulfate cement for
      thoracolumbar burst fractures.
AB  - OBJECTIVE: To evaluate the biomechanical performance of vertebroplasty using
      calcium sulfate cement for thoracolumbar burst fractures. METHODS: Sixteen bovine
      thoracolumbar spines (T11-L1) were divided into 4 groups (A,B,C and D). After
      burst-fracture model was created, 12 vertebral bodies in Groups A, B and C were
      augmented with calcium sulfate cement (CSC), calcium phosphate cement (CPC) and
      polymethylmethacrylate (PMMA) bone cement, respectively. Each anterior vertebral
      body height was measured with a caliper at 4 time points: intact conditions
      (HInt), post-fracture (HFr), post-reduction (HRe) and post-vertebroplasty (HVP).
      The filling volume of 3 different bone cements was also measured. Each vertebral
      body was compressed at 0.5 mm/s using a hinged plating system on a materials
      testing machine to 50% of the post-vertebroplasty height to determine strength
      and stiffness. Difference was checked using t test or One-way ANOVA. RESULTS: The
      average strike energy was 66.2 J. Vertebroplasty with different cements could
      sustain vertebral height. The average filling volume of bone cement in 3 groups
      was 4.35 ml (CSC), 3.72 ml (CPC) and 3.95 ml (PMMA), respectively, and there was
      no statistically significant difference among them (P larger than 0.05).
      Vertebroplasty with PMMA completely restored strength (116%) and stiffness
      (105%). CSC or CPC partly recovered vertebral strength and stiffness. However,
      greater strength restoration was got with CSC (1659 N) as compared with CPC
      (1011N, P less than 0.01). Regarding stiffness, differences between CSC (140
      N/mm+/-40 N/mm)and the other two bone cements (CPC:148 N/mm+/-33 N/mm, PMMA:236
      N/mm+/-97 N/mm) were not significant (P larger than 0.05). CONCLUSIONS: For a
      burst-fracture of calf spine, use of CSC for vertebroplasty yields similar
      vertebral stiffness as compared with PMMA or CPC. Although augmentation with CSC
      partly obtains the normal strength, this treatment still can be applied in
      thoracolumbar burst fractures with other instrumental devices in light of its
      bioactivation.

PMID- 18045513
TI  - A follow-up study of arthroscopic combined reconstruction of anterior and
      posterior cruciate ligaments with allograft patellar tendon.
AB  - OBJECTIVE: To evaluate the therapeutic effect of combined reconstruction of
      anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL)
      simultaneously by using allograft patellar tendon under arthroscopy. METHODS:
      From May 2003 to November 2005, 10 cases of ruptured ACL and PCL were fixated
      with compressed screws and reconstructed under arthroscopy with allograft
      patellar tendon simultaneously. The clinical results were evaluated according to
      IKDC, Lysholm, and Tegner clinical rating scales. RESULTS: All patients were
      followed up for 12-30 months (mean: 18 months). At the last follow-up, there was
      no knee extension limitation and knee flexion was between 120 degree and 135
      degree,with an average of 128.38 degree. The Lysholm score of the 10 cases was
      66.5+/-5.6 before operation and 89.8+/-3.4 at last follow up. The difference was
      statistically significant (P less than 0.01). The average Tegner activity score
      decreased from 6.9+/-1.7 (range: 4-9) before injury to 5.5+/-1.6 (rang:2-9) at
      the follow-up (P equal to 0.53). At the end of follow-up, IKDC score was graded
      as A in 4 cases (40.0%), B in 5 (50.0%), and C in 1 (10.0%). Of the 10 patients,
      8 returned to the same sports level as before injury and 2 were under the level.
      CONCLUSION: Arthroscopic combined reconstruction of ACL and PCL with allograft
      patellar tendon has the advantages of minimal trauma in surgery and reliable
      satisfactory outcome.

PMID- 18045514
TI  - Effect of allograft compound vertebra on vertebral reconstruction in rabbits.
AB  - OBJECTIVE: To study the effect of allograft compound vertebra on vertebral
      reconstruction in rabbits so as to provide biomechanical direction for
      manufacturing and selecting vertebral reconstruction materials. METHODS: Twenty
      five healthy New Zealand white rabbits were divided randomly into three groups:
      normal group (Group A, n equal to 5),iliac bone graft group (Group B, n equal to
      10) and allograft compound vertebra group (Group C, equal to 10). After C4 was
      resected, iliac bone implantation and allograft bone cage transplantation were
      fulfilled in Group B and Group C, respectively. Every 5 rabbits from Group B and
      Group C were selected to test the biomechanical strength and biological activity
      one and two months postoperatively. RESULTS: No significant statistical
      difference was found between Group A and Group C one and two months
      postoperatively (P larger than 0.05). The biomechanical strength of Group B was
      much weaker than that of Group A and Group C one month postoperatively (P less
      than 0.05), but at two months postoperatively, no statistical difference was
      found among the three groups. The biological activity and vertebral moulding
      ability of Group C were better than those of Group B at one and two months
      postoperatively. CONCLUSIONS: Compound vertebra, which is made up of allograft
      cortical bone cage and autogenous cancellous bone, shows instantaneous and
      permanent biomechanical stability and biological activity, therefore, it is an
      ideal material for vertebral reconstruction.

PMID- 18045515
TI  - Regulation of vascular endothelial growth factor on the expression of fracture
      healing-related factors.
AB  - OBJECTIVE: To study the effect of vascular endothelial growth factor (VEGF)and
      anti-VEGF on the expression of fracture healing-related factors and observe
      pathological changes at fractured sites. METHODS: Fracture models were
      established in 105 New Zealand white rabbits and they were randomly divided into
      control group, VEGF group and anti-VEGF group. The relevant factors expression at
      fractured sites was assayed and pathological changes were observed in decalcified
      samples at 8, 24, 72 hours and 1,3,5,8 weeks after fracture. RESULTS: After
      application of VEGF, the expression of BMP appeared earlier and expression time
      lasted longer. On the contrary, anti-VEGF completely inhibited the expression of
      BMP. The fractured sites were filled with fibrous callus, cartilaginous callus
      and bony callus at the 3rd week and woven bone was constructed at the 5th week.
      Fracture healing was accomplished at the 8th week in VEGF group. In anti-VEGF
      polyclonal antibody group, cellular necrosis increased at early period.
      Continuous focal necrosis was seen in the fractured sites from the 1st week to
      5th week. Vascularization reduced obviously at the 3rd week. CONCLUSIONS:
      Fracture healing is a result of mutual regulation and coordination among many
      factors. VEGF may be an important factor in fracture healing.

PMID- 18045516
TI  - Pedicle screw fixation against burst fracture of thoracolumbar vertebrae.
AB  - OBJECTIVE: To analyze the application of vertebral pedicle screw fixation in the
      treatment of burst fracture of thoracolumbar vertebrae. METHODS: A total of 48
      cases (31 males and 17 females, aged from 18-72 years, mean: 41.3 years) with
      thoracolumbar vertebrae burst fracture were treated by pedicle screw system since
      January 2004. According to the AO classification of thoracolumbar vertebrae
      fracture, there are 36 cases of Type A, 9 of Type B and 3 of Type C. RESULTS: All
      patients were followed up for 6-25 months (average 12 months), no secondary nerve
      root injury, spinal cord injury, loosening or breakage of pedicle screw were
      observed. The nerve function of 29 patients with cauda equina nerve injury was
      restored to different degrees. The vertebral body height returned to normal level
      and posterior process angle was rectified after operation. CONCLUSIONS: The
      vertebral pedicle screw internal fixation was technologically applicable, which
      can efficiently reposition and stabilize the bursting fractured vertebrae,
      indirectly decompress canalis spinalis, maintain spine stability, scatter stress
      of screw system, reduce the risk of loosening or breakage of screw and loss of
      vertebral height, and prevent the formation of posterior convex after operation.

PMID- 18045517
TI  - Construction and identification of immortalized rat astrocyte cell line
      expressing enkephalin.
AB  - OBJECTIVE: To provide a sound cell source for further ex-vivo gene therapy for
      chronic pain, we attempt to develop an immortalized rat astrocyte cell line that
      expresses enkephalin regulated by doxycycline. METHODS: Retrovirus infection
      method was employed to develop an immortalized rat astrocyte cell line that could
      express enkephalin regulated by doxycycline. The hPPE gene expression level of
      immoralized astroyte cells (IAC)/ hPPE was detected by RT-PCR, indirect
      immunofluorescence staining and radioimmunoassay. RESULTS: IAC carrying Tet-on
      system transfected with preproenkephalin gene could secrete enkephalin that was
      regulated by doxycycline in a dose-dependent manner and hPPE gene activation
      could be repeated in on-off-on cycles through administration or removal of
      doxycycline. CONCLUSION: An immortalized rat astrocyte cell line that secrete
      enkephalin under the control of doxycycline is established successfully, which
      provides a research basis for transgenic cell transplantation for analgesia.

PMID- 18045518
TI  - First aid strategy for severe traumatic patients in hospital.
AB  - OBJECTIVE: To study the emergency management principles of severe trauma in
      hospital (injury severity score larger than or equal to 16). METHODS: We used
      "ATP principle" to manage severe traumatic patients. The ATP principle is
      composed of: 1) attending surgeons offering initial management (A); 2) teamwork
      commencement immediately after patients admitted to hospital (T); 3) parallel
      principle, ie, emergency resuscitation, evaluation and laboratory test performed
      simultaneously (P). Clinical effects before and after applying ATP principle were
      retrospectively analyzed and compared. RESULTS: During January 1, 2002 to
      December 31, 2003, 338 patients were treated without applying ATP principle, in
      which ISS was 25.9+/-6.4, 152 cases died with the mortality being 39.2%, and the
      time stayed in emergency department and the time to operation room after
      admission were (102.8+/-16.7) min, (140.3+/-20.6) min, respectively. During
      January 1, 2004 to December 31, 2005, 438 patients were treated based on ATP
      principle, in which ISS was 28.6+/-7.8, 87 cases died with the mortality being
      19.9%, and the time in emergency department and the time to operation room after
      admission were (69.5+/-11.5) min, (89.6+/-9.3) min, respectively. ISS showed no
      significant difference between the two groups (P larger than 0.05) but the
      mortality, the time stayed in emergency department and the time to operation room
      after admission were greatly reduced and showed significant difference between
      the two groups (P less than 0.05). CONCLUSIONS: Applying ATP principle to treat
      severe traumatic patients can shorten emergency treatment time in hospital and
      decrease mortality.

PMID- 18045519
TI  - Relationship among bone mineral density, collagen composition, and biomechanical
      properties of callus in the healing of osteoporotic fracture.
AB  - OBJECTIVE: To study the change and relationship among bone mineral density (BMD),
      collagen composition and biomechanical properties of the callus in the healing
      process of osteoporotic fracture. METHODS: The osteoporotic rat model and
      fracture model were established through bilateral ovariectomy (OVX) and osteotomy
      of the middle shaft of the right hind tibiae, respectively. Ninety female SD rats
      were randomly divided into OVX group and sham group. With the samples of blood
      and callus, roentgenographic and histological observation were performed for the
      assessment of the healing progress of the fracture, and the serum concentration
      of TRAP-5b, proportion of type I collagen, BMD and biomechanical properties of
      the callus were measured. RESULTS: The OVX group experienced a significant delay
      of fracture healing. The mean serum concentration of TRAP-5b of rats in the OVX
      group was much higher than that in the sham group after the operation (P less
      than 0.05), but the difference at the same time point after fracture was smaller
      than that before fracture (P less than 0.05). The BMD of the callus in both
      groups reached the peak value at the 6 th week after fracture while the
      proportion of the type I collagen and the biomechanical strength reached the peak
      at the 8th week. CONCLUSIONS: The deficiency of estrogen after the ovariectomy
      could induce the up-regulation of the osteoclasts activities, whereas the potency
      of further activation after fracture was depressed. Although the synthesis of
      collagen together with its mineralization determines the biomechanical properties
      of new bone, the accumulation of collagen could be assessed as an index in the
      prediction of biomechanical strength of bones independent of the bone mineral
      deposition.

PMID- 18045520
TI  - Surgery for posttraumatic syringomyelia: a retrospective study of seven patients.
AB  - OBJECTIVE: To analyze retrospectively the clinical symptoms, signs, radiological
      findings and results of treatment of posttraumatic syringomyelia. METHODS: The
      data of 7 patients with posttraumatic syringomyelia confirmed by computerized
      tomography (CT) and magnetic resonance imaging (MRI) in our hospital between 1999
      and 2004 were reviewed retrospectively. The patients underwent decompressive
      laminectomy or syringo-subarachnoid (S-S) shunting with microsurgery. Long-term
      follow-up was available (range: 13-65 months). RESULTS: The major clinical
      manifestations of posttraumatic syringomyelia usually included the onset of
      increasing signs and the development of new symptoms after an apparently stable
      period. The clinical symptoms included pain, sensory disturbance, weakness, and
      problems in autonomic nerves. Syrinx existed merely at the cervical level in 4
      cases and extended downward to the thoracic levels in the other 3 cases. One case
      underwent decompressive laminectomy, 6 cases were treated by S-S shunting. During
      the early postoperative period, all the patients showed an improvement of
      symptoms of syrinx without major complication or death. The decreased size or
      collapse of the syrinx was demonstrated by postoperative MRI. CONCLUSIONS:
      Posttraumatic syringomyelia is a disabling sequela of spinal cord injury,
      developing months to years after spinal injury. MRI is the standard diagnostic
      technique for syringomyelia. The patients with posttraumatic syringomyelia
      combined with progressive neurological deterioration should be treated with
      operations. S-S shunting procedure is effective in some patients with
      posttraumatic syringomyelia. Decompressive procedure may be an alternative
      primary surgical treatment for patients with kyphosis and cord compression.

PMID- 18045521
TI  - Orthopedic trauma of limbs associated with vascular injuries.
AB  - OBJECTIVE: To evaluate the treatment for patients with major vascular injuries
      associated with traumatic orthopedic injuries. METHODS: A total of 196 patients,
      aged from 4-67 years with the mean age of 29.88 years, had major vascular
      injuries associated with traumatic orthopedic injuries and were treated in our
      hospital in a period of 44 years. The most common mechanism of trauma was blunt
      trauma (67.3%), open injuries accounted for 32.4% and 54.5% of the injuries were
      located in the lower extremities. The vascular injury frequently happened in the
      femoral artery (26.7%) and popliteal artery (20.3%). The treatment principle
      consisted of aggressive resuscitation, Doppler imaging and stable bone internal
      fixation with subsequent vascular repair and debridement. The vascular repair for
      injuries included end-to-end anastomosis (80 cases, 39.6%), interpositional vein
      graft (94, 46.5%), vascular decompression through fracture distraction (18,
      8.9%), arterial ligation (6, 3.0%), vein patch (2, 1.0%), bypass graft (2, 1.0%),
      venous repair including autogenous vein graft (9, 24.3%) and ligation (28, 75.7%)
      and prophylactical fasciotomy (15, 7.4%). Postoperative amputation was performed
      in 16 cases (16.3%). RESULTS: No intraoperative death was observed and all
      fractures united within 6 months. Limbs were salvaged in 180 patients (91.8%).
      Among these patients, early complications were found in 19 patients (9.7%) and
      late complications were observed in 8 patients (4.1%). CONCLUSIONS: A well
      organized approach, based on a specific treatment principle, not only improves
      clinical outcome but also does good to excellent functional recovery for patients
      with severe orthopedic injuries and concomitant vascular lesion.

PMID- 18045522
TI  - Research progress in mechanism of traumatic brain injury affecting speed of
      fracture healing.
AB  - In patients who have sustained traumatic brain injury with associated extremity
      fracture, there is often a clinical perception that the rate of new bone
      formation around the fracture site increases.(1) An overgrowth of callus is
      observed and ectopic ossification even occurs in the muscle,(2) but the mechanism
      remains unclear. Whether this rapidly-formed new bone is fracture callus or a
      variant of heterotopic ossification, a common complication of traumatic brain
      injury, is the subject of some debates.(3) It is generally believed that the
      process of fracture healing is a recapitulation of normal embryonic
      osteogenesis,(4) i.e. ,a series of changes in the intracellular and extracellular
      matrix, which start from the injury of cells, blood vessels and bone matrix to a
      complete reconstruction of the bone.(5) It is a complex process influenced by
      multi-level and multi-route regulations of the general and local environments in
      the body, and many growth factors participate in this process, which is the base
      of bone healing;(6) whatever methods are used to promote bone healing, they are
      based on accelerating the changes of growth factors.(7) So it is worth making a
      thorough study on the mechanism, by which traumatic brain injury influences the
      expression levels of growth factors and consequently affects the speed of bone
      healing.

PMID- 18045523
TI  - Abdominal splenosis: CT and MRI features of 2 cases.
AB  - Splenosis is ectopic autotransplantation of splenic tissue after splenic trauma
      or surgery.(1) The most frequent locations are the surface of visceral peritoneum
      and parietal peritoneum. Liver and retroperitoneum are rarely involved.(1,2) We
      present here 2 cases of splenosis involving the liver and retroperitoneum with
      clinical information, imaging findings, and literature review.

PMID- 18045524
TI  - ChIP-Seq data reveal nucleosome architecture of human promoters.

PMID- 18045526
TI  - Induction of pluripotency: from mouse to human.
AB  - In this issue of Cell, Takahashi et al. (2007) transfer their seminal work on
      somatic cell reprogramming from the mouse to human. By overexpressing the
      transcription factor quartet of Oct4, Sox2, Klf4, and c-Myc in adult human
      fibroblasts, they successfully isolate human pluripotent stem cells that resemble
      human embryonic stem cells by all measured criteria. This is a significant
      turning point in nuclear reprogramming research with broad implications for
      generating patient-specific pluripotent stem cells for research and therapeutic
      applications.

PMID- 18045527
TI  - DNA mismanagement leads to immune system oversight.
AB  - Trex1, a major 3' DNA exonuclease in mammalian cells, has been thought to act
      primarily in DNA replication or repair. Surprisingly, the major phenotype
      resulting from Trex1 deficiency in humans and mice is a chronic inflammatory
      disease. In this issue, Yang et al. (2007) report that Trex1 deficiency causes
      chronic activation of the ATM-dependent DNA-damage checkpoint and accumulation of
      a discrete single-stranded DNA species in the cytoplasm, either of which could
      contribute to chronic inflammation.

PMID- 18045528
TI  - tRNA traffic meets a cell-cycle checkpoint.
AB  - The molecular pathways linking DNA-damage checkpoint proteins to cell-cycle
      progression remain largely unresolved. Findings by Ghavidel et al. (2007)
      reported in this issue suggest that tRNA trafficking and the transcription factor
      Gcn4 are key intermediates in the process by which yeast cells detect DNA damage
      and delay cell-cycle progression at the G1 to S phase transition.

PMID- 18045529
TI  - Entosis: it's a cell-eat-cell world.
AB  - In this issue, Overholtzer et al. (2007) describe a new nonapoptotic cell death
      pathway termed "entosis" in mammary epithelial cells that have detached from the
      extracellular matrix (ECM). Given that surviving detachment from the ECM is an
      event associated with the progression of epithelial cancers, entosis--along with
      apoptosis--may contribute to tumor suppression by promoting the elimination of
      cancer cells.

PMID- 18045530
TI  - Stem cells on patrol.
AB  - Hematopoietic stem cells (HSCs) exist in the bone marrow and circulate in the
      blood. In this issue, Massberg et al. (2007) report that HSCs also travel through
      the lymphatic system. Furthermore, migration of HSCs--which express Toll-like
      receptors--allows the recognition of pathogenic molecules in peripheral tissues
      thereby promoting the local generation of innate immune cells at the site of
      infection.

PMID- 18045531
TI  - cis-Regulatory elements within the odorant receptor coding region.
AB  - Complex regulatory mechanisms lead to the expression in each olfactory neuron of
      one allele of only one of the 1000 odorant receptor (OR) genes. In this issue,
      Nguyen et al. (2007) provide evidence that regulatory elements residing within
      the coding region of OR genes are involved in the singularity of OR gene
      expression.

PMID- 18045532
TI  - Cytokinesis: placing and making the final cut.
AB  - Cytokinesis is the process by which cells physically separate after the
      duplication and spatial segregation of the genetic material. A number of general
      principles apply to this process. First the microtubule cytoskeleton plays an
      important role in the choice and positioning of the division site. Once the site
      is chosen, the local assembly of the actomyosin contractile ring remodels the
      plasma membrane. Finally, membrane trafficking to and membrane fusion at the
      division site cause the physical separation of the daughter cells, a process
      termed abscission. Here we will discuss recent advances in our understanding of
      the mechanisms of cytokinesis in animals, yeast, and plants.

PMID- 18045533
TI  - Trex1 exonuclease degrades ssDNA to prevent chronic checkpoint activation and
      autoimmune disease.
AB  - Trex1 is the major 3' DNA exonuclease in mammalian cells, and mutations in the
      human TREX1 gene can cause Aicardi-Goutieres syndrome, characterized by perturbed
      immunity. Similarly, Trex1(-/-) mice have an autoinflammatory phenotype; however,
      the mechanism of Trex1-deficient disease is unknown. We report that Trex1,
      ordinarily associated with the endoplasmic reticulum (ER), relocalizes to the S
      phase nucleus after gamma irradiation or hydroxyurea treatment. Notably, Trex1
      deficient cells show defective G1/S transition and chronic ATM-dependent
      checkpoint activation, even in the absence of exogenous stress, correlating with
      persistent single-stranded DNA molecules produced in S phase, which accumulate in
      the ER. Our data indicate that Trex1 acts on a single-stranded DNA polynucleotide
      species generated from processing of aberrant replication intermediates to
      attenuate DNA damage checkpoint signaling and prevent pathological immune
      activation.

PMID- 18045534
TI  - Impaired tRNA nuclear export links DNA damage and cell-cycle checkpoint.
AB  - In response to genotoxic stress, cells evoke a plethora of physiological
      responses collectively aimed at enhancing viability and maintaining the integrity
      of the genome. Here, we report that unspliced tRNA rapidly accumulates in the
      nuclei of yeast Saccharomyces cerevisiae after DNA damage. This response requires
      an intact MEC1- and RAD53-dependent signaling pathway that impedes the nuclear
      export of intron-containing tRNA via differential relocalization of the
      karyopherin Los1 to the cytoplasm. The accumulation of unspliced tRNA in the
      nucleus signals the activation of Gcn4 transcription factor, which, in turn,
      contributes to cell-cycle arrest in G1 in part by delaying accumulation of the
      cyclin Cln2. The regulated nucleocytoplasmic tRNA trafficking thus constitutes an
      integral physiological adaptation to DNA damage. These data further illustrate
      how signal-mediated crosstalk between distinct functional modules, namely, tRNA
      nucleocytoplasmic trafficking, protein synthesis, and checkpoint execution,
      allows for functional coupling of tRNA biogenesis and cell-cycle progression.

PMID- 18045535
TI  - Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates
      selective gene regulation.
AB  - NF-kappaB is a DNA-binding protein complex that transduces a variety of
      activating signals from the cytoplasm to specific sets of target genes. To
      understand the preferential recruitment of NF-kappaB to specific gene regulatory
      sites, we used NF-kappaB p65 in a tandem affinity purification and mass
      spectrometry proteomic screen. We identified ribosomal protein S3 (RPS3), a KH
      domain protein, as a non-Rel subunit of p65 homodimer and p65-p50 heterodimer DNA
      binding complexes that synergistically enhances DNA binding. RPS3 knockdown
      impaired NF-kappaB-mediated transcription of selected p65 target genes but not
      nuclear shuttling or global protein translation. Rather, lymphocyte-activating
      stimuli caused nuclear translocation of RPS3, parallel to p65, to form part of NF
      kappaB bound to specific regulatory sites in chromatin. Thus, RPS3 is an
      essential but previously unknown subunit of NF-kappaB involved in the regulation
      of key genes in rapid cellular activation responses. Our observations provide
      insight into how NF-kappaB selectively controls gene expression.

PMID- 18045536
TI  - Spatiotemporal coupling of cAMP transporter to CFTR chloride channel function in
      the gut epithelia.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated
      chloride channel localized at apical cell membranes and exists in macromolecular
      complexes with a variety of signaling and transporter molecules. Here, we report
      that the multidrug resistance protein 4 (MRP4), a cAMP transporter, functionally
      and physically associates with CFTR. Adenosine-stimulated CFTR-mediated chloride
      currents are potentiated by MRP4 inhibition, and this potentiation is directly
      coupled to attenuated cAMP efflux through the apical cAMP transporter. CFTR
      single-channel recordings and FRET-based intracellular cAMP dynamics suggest that
      a compartmentalized coupling of cAMP transporter and CFTR occurs via the PDZ
      scaffolding protein, PDZK1, forming a macromolecular complex at apical surfaces
      of gut epithelia. Disrupting this complex abrogates the functional coupling of
      cAMP transporter activity to CFTR function. Mrp4 knockout mice are more prone to
      CFTR-mediated secretory diarrhea. Our findings have important implications for
      disorders such as inflammatory bowel disease and secretory diarrhea.

PMID- 18045537
TI  - Force-induced bidirectional stepping of cytoplasmic dynein.
AB  - Cytoplasmic dynein is a minus-end-directed microtubule motor whose mechanism of
      movement remains poorly understood. Here, we use optical tweezers to examine the
      force-dependent stepping behavior of yeast cytoplasmic dynein. We find that
      dynein primarily advances in 8 nm increments but takes other sized steps (4-24
      nm) as well. An opposing force induces more frequent backward stepping by dynein,
      and the motor walks backward toward the microtubule plus end at loads above its
      stall force of 7 pN. Remarkably, in the absence of ATP, dynein steps processively
      along microtubules under an external load, with less force required for minus-end
      than for plus-end-directed movement. This nucleotide-independent walking reveals
      that force alone can drive repetitive microtubule detachment-attachment cycles of
      dynein's motor domains. These results suggest a model for how dynein's two motor
      domains coordinate their activities during normal processive motility and provide
      new clues for understanding dynein-based motility in living cells.

PMID- 18045538
TI  - A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion.
AB  - Epithelial cells require attachment to extracellular matrix (ECM) to suppress an
      apoptotic cell death program termed anoikis. Here we describe a nonapoptotic cell
      death program in matrix-detached cells that is initiated by a previously
      unrecognized and unusual process involving the invasion of one cell into another,
      leading to a transient state in which a live cell is contained within a
      neighboring host cell. Live internalized cells are either degraded by lysosomal
      enzymes or released. We term this cell internalization process entosis and
      present evidence for entosis as a mechanism underlying the commonly observed
      "cell-in-cell" cytological feature in human cancers. Further we propose that
      entosis is driven by compaction force associated with adherens junction formation
      in the absence of integrin engagement and may represent an intrinsic tumor
      suppression mechanism for cells that are detached from ECM.

PMID- 18045539
TI  - Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1
      signal.
AB  - BMP receptors determine the intensity of BMP signals via Smad1 C-terminal
      phosphorylations. Here we show that a finely controlled cell biological pathway
      terminates this activity. The duration of the activated pSmad1(Cter) signal was
      regulated by sequential Smad1 linker region phosphorylations at conserved MAPK
      and GSK3 sites required for its polyubiquitinylation and transport to the
      centrosome. Proteasomal degradation of activated Smad1 and total
      polyubiquitinated proteins took place in the centrosome. Inhibitors of the Erk,
      p38, and JNK MAPKs, as well as GSK3 inhibitors, prolonged the duration of a pulse
      of BMP7. Wnt signaling decreased pSmad1(GSK3) antigen levels and redistributed it
      from the centrosome to cytoplasmic LRP6 signalosomes. In Xenopus embryos, it was
      found that Wnts induce epidermis and that this required an active BMP-Smad
      pathway. Epistatic experiments suggested that the dorsoventral (BMP) and
      anteroposterior (Wnt/GSK3) patterning gradients are integrated at the level of
      Smad1 phosphorylations during embryonic pattern formation.

PMID- 18045540
TI  - Immunosurveillance by hematopoietic progenitor cells trafficking through blood,
      lymph, and peripheral tissues.
AB  - Constitutive egress of bone marrow (BM)-resident hematopoietic stem and
      progenitor cells (HSPCs) into the blood is a well-established phenomenon, but the
      ultimate fate and functional relevance of circulating HSPCs is largely unknown.
      We show that mouse thoracic duct (TD) lymph contains HSPCs that possess short-
      and long-term multilineage reconstitution capacity. TD-derived HSPCs originate in
      the BM, enter the blood, and traffic to multiple peripheral organs, where they
      reside for at least 36 hr before entering draining lymphatics to return to the
      blood and, eventually, the BM. HSPC egress from extramedullary tissues into lymph
      depends on sphingosine-1-phosphate receptors. Migratory HSPCs proliferate within
      extramedullary tissues and give rise to tissue-resident myeloid cells,
      preferentially dendritic cells. HSPC differentiation is amplified upon exposure
      to Toll-like receptor agonists. Thus, HSPCs can survey peripheral organs and can
      foster the local production of tissue-resident innate immune cells under both
      steady-state conditions and in response to inflammatory signals.

PMID- 18045541
TI  - Prominent roles for odorant receptor coding sequences in allelic exclusion.
AB  - Mammalian odorant receptors (ORs) are crucial for establishing the functional
      organization of the olfactory system, but the mechanisms controlling their
      expression remain largely unexplained. Here, we utilized a transgenic approach to
      explore OR gene regulation. We determined that although olfactory sensory neurons
      (OSNs) are capable of supporting expression of multiple functional ORs, several
      levels of control ensure that each neuron normally expresses only a single
      odorant receptor. Surprisingly, this regulation extends beyond endogenous ORs
      even preventing expression of transgenes consisting of OR-coding sequences driven
      by synthetic promoters. Thus, part of the intrinsic feedback system must rely on
      elements present in the OR-coding sequence. Notably, by expressing the same
      transgenic ORs precociously in immature neurons, we have overcome this
      suppression and established a generic method to express any OR in approximately
      90% of OSNs. These results provide important insights into the hierarchy of OR
      gene expression and the vital role of the OR-coding sequence in this regulation.

PMID- 18045542
TI  - SnapShot: EGFR signaling pathway.

PMID- 18045544
TI  - Oxidative stress causes a decline in lysosomal integrity during hypothermic
      incubation of rat hepatocytes.
AB  - Oxidative stress during cold preservation has been identified as a significant
      cause of cell injury but the process by which injury occurs is poorly understood.
      We examined loss of lysosomal integrity as a possible cause of cell injury during
      extended cold storage of isolated rat hepatocytes. After 21 h of hypothermia,
      there was a marked decline in lysosomal integrity, which was correlated with an
      increase in lipid peroxidation. When lipid peroxidation was prevented with the
      antioxidant Trolox (a vitamin E analog) or the iron chelator desferrioxamine,
      lysosomal integrity was preserved. In contrast, increasing lysosomal iron with
      ferric chloride caused an increase in lipid peroxidation and decreased lysosomal
      integrity. Loss of lysosomal integrity during cold preservation in this
      experimental model was consistent with iron-initiated oxidative stress. The
      progressive loss of lysosomal integrity during hypothermic incubation has the
      potential to affect liver function after transplantation.

PMID- 18045543
TI  - Peroxynitrite inhibits myofibrillar protein function in an in vitro assay of
      motility.
AB  - We determined the effects of peroxynitrite (ONOO-) on cardiac myosin, actin, and
      thin filaments in order to more clearly understand the impact of this reactive
      compound in ischemia/reperfusion injury and heart failure. Actin filaments,
      native thin filaments, and alpha-cardiac myosin from rat hearts were exposed to
      ONOO- in the presence of 2 mM bicarbonate. Filament velocities over myosin,
      calcium sensitivity, and relative force generated by myosin were assessed in an
      in vitro motility assay in the absence of reducing agents. ONOO- concentrations >
      or =10 microM significantly reduced the velocities of thin filaments or bare
      actin filaments over alpha-cardiac myosin when any of these proteins were exposed
      individually. These functional deficits were linearly related to the degree of
      tyrosine nitration, with myosin being the most sensitive. However, at 10 microM
      ONOO- the calcium sensitivity of thin filaments remained unchanged. Cotreatment
      of myosin and thin filaments, analogous to the in vivo situation, resulted in a
      significantly greater functional deficit. The load supported by myosin after ONOO
      exposure was estimated using mixtures experiments to be increased threefold.
      These data suggest that nitration of myofibrillar proteins can contribute to
      cardiac contractile dysfunction in pathologic states in which ONOO- is liberated.

PMID- 18045545
TI  - Selenium inhibits 15-hydroperoxyoctadecadienoic acid-induced intracellular
      adhesion molecule expression in aortic endothelial cells.
AB  - Increased intracellular adhesion molecule 1 (ICAM-1) expression and enhanced
      monocyte recruitment to the endothelium are critical steps in the early
      development of atherosclerosis. The 15-lipoxygenase 1 (15-LOX1) pathway can
      generate several proinflammatory eicosanoids that are known to enhance ICAM-1
      expression within the vascular endothelium. Oxidative stress can exacerbate
      endothelial cell inflammatory responses by modifying arachidonic acid metabolism
      through the 15-LOX1 pathway. Because selenium (Se) influences the oxidant status
      of cells and can modify the expression of eicosanoids, we investigated the role
      of this micronutrient in modifying ICAM-1 expression as a consequence of enhanced
      15-LOX1 activity. Se supplementation reduced ICAM-1 expression in bovine aortic
      endothelial cells, an effect that was reversed with 15-LOX1 overexpression or
      treatment with exogenous 15-hydroperoxyoctadecadienoic acid (15-HPETE). ICAM-1
      expression increased proportionately when intracellular15-HPETE levels were
      allowed to accumulate. However, changes in intracellular 15-HETE levels did not
      seem to affect ICAM-1 expression regardless of Se status. Our results indicate
      that Se supplementation can reduce 15-HPETE-induced expression of ICAM-1 by
      controlling the intracellular accumulation of this fatty acid hydroperoxide in
      endothelial cells.

PMID- 18045546
TI  - Neurotoxicity from glutathione depletion is mediated by Cu-dependent p53
      activation.
AB  - Loss of intracellular neuronal glutathione (GSH) is an important feature of
      neurodegenerative disorders including Alzheimer's disease, Parkinson's disease,
      and amyotrophic lateral sclerosis. The consequences of GSH depletion include
      increased oxidative damage to proteins, lipids, and DNA and subsequent cytotoxic
      effects. GSH is also an important modulator of cellular copper (Cu) homeostasis
      and altered Cu metabolism is central to the pathology of several
      neurodegenerative diseases. The cytotoxic effects of Cu in cells depleted of GSH
      are not well understood. We have previously reported that depletion of neuronal
      GSH levels results in cell death from trace levels of extracellular Cu due to
      elevated Cu(I)-mediated free radical production. In this study we further
      examined the molecular pathway of trace Cu toxicity in neurons and fibroblasts
      depleted of GSH. Treatment of primary cortical neurons or 3T3 fibroblasts with
      the glutathione synthetase inhibitor buthionine sulfoximine resulted in
      substantial loss of intracellular GSH and increased cytotoxicity. We found that
      both neurons and fibroblasts revealed increased expression and activation of p53
      after depletion of GSH. The increased p53 activity was induced by extracellular
      trace Cu. Furthermore, we showed that in GSH-depleted cells, Cu induced an
      increase in oxidative stress resulting in DNA damage and activation of p53
      dependent cell death. These findings may have important implications for
      neurodegenerative disorders that involve GSH depletion and aberrant Cu
      metabolism.

PMID- 18045547
TI  - The roles of thiol-derived radicals in the use of 2',7'
      dichlorodihydrofluorescein as a probe for oxidative stress.
AB  - 2',7'-Dichlorodihydrofluorescein (DCFH2) is one of the most widely used probes
      for detecting intracellular oxidative stress, but requires a catalyst to be
      oxidized by hydrogen peroxide or superoxide and reacts nonspecifically with
      oxidizing radicals. Thiyl radicals are produced when many radicals are "repaired"
      by thiols, but are oxidizing agents and thus potentially capable of oxidizing
      DCFH2. The aim of this study was to investigate the reactivity of thiol-derived
      radicals toward DCFH2 and its oxidized, fluorescent form 2',7'
      dichlorofluorescein (DCF). Thiyl radicals derived from oxidation of glutathione
      (GSH) or cysteine (CysSH) oxidized DCFH2 with rate constants at pH 7.4 of
      approximately 4 or approximately 2x10(7) M(-1) s(-1), respectively. Both the
      rates of oxidation and the yields of DCF were pH-dependent. Glutathione-derived
      radicals interacted with DCF, resulting in the formation of DCFH* absorbing at
      390 nm and loss of fluorescence; in contrast, cysteine-derived radicals did not
      cause any depletion of DCF fluorescence. We postulate that the observed apparent
      difference in reactivity between GS* and CysS* toward DCF is related to the
      formation of carbon-centered, reducing radicals from base-catalyzed isomerization
      of GS*. DCF formation from interaction of DCFH2 with GS* was inhibited by oxygen
      in a concentration-dependent manner over the physiological range. These data
      indicate that in applying DCFH2 to measure oxidizing radicals in biological
      systems, we have to consider not only the initial competition between thiols and
      DCFH2 for the oxidizing radicals, but also subsequent reactions of thiol-derived
      radicals, together with variables--including pH and oxygen concentration--which
      control thiyl radical chemistry.

PMID- 18045548
TI  - Phenyl-tert-butylnitrone induces tumor regression and decreases angiogenesis in a
      C6 rat glioma model.
AB  - The prognosis of patients who are diagnosed with glioblastoma multiforme is very
      poor, due to the difficulty of an early and accurate diagnosis and the lack of
      currently efficient therapeutic compounds. The efficacy of phenyl-tert
      butylnitrone (PBN) as a potential anti-glioma therapeutic drug was assessed by
      magnetic resonance (MR) imaging (T(1)/T(2)-weighted imaging) and MR angiography
      (time-of-flight imaging, in conjunction with a Mathematica-based program) methods
      by monitoring morphologic properties, growth patterns, and angiogenic behaviors
      of a moderately aggressive rat C6 glioma model. MR results from untreated rats
      showed the diffusive invasiveness of C6 gliomas, with some associated
      angiogenesis. PBN administration as a pretreatment was found to clearly induce a
      decrease in growth rate and tumor regression as well as preventing angiogenesis.
      This compound even had a 40% efficiency in reducing well-established tumors. MR
      findings rivaled those from histology and angiogenesis marker immunostaining
      evaluations. In this study we demonstrated the efficiency of PBN as a potential
      anti-glioma drug and found it to inhibit tumor cell proliferation and prevent
      vascular alterations in early stages of glioma progression. The MR methods that
      we used also proved to be particularly suitable in following the angiogenic
      behavior and treatment response of a potential anti-glioma agent in a rat C6
      glioma model.

PMID- 18045549
TI  - Beneficial effect of a short-acting NO donor for the prevention of neointimal
      hyperplasia.
AB  - Nitric oxide (NO)-based therapies effectively inhibit neointimal hyperplasia in
      animal models of arterial injury and bypass grafting, but are not available
      clinically. We created a simple, effective, locally applied NO-eluting therapy to
      prevent restenosis after vascular procedures. We investigated the efficacy of
      perivascular delivery of two distinctly different diazeniumdiolate NO donors, 1
      [2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (short half
      life) and diazeniumdiolated poly(acrylonitrile) (PAN/NO) (long half-life), in
      powder or gel form (30% poloxamer 407), at inhibiting neointimal hyperplasia
      using the rat carotid artery injury model. Two weeks postinjury, all of the NO
      eluting therapies successfully reduced neointimal hyperplasia. However, most
      dramatically, PROLI/NO powder reduced intimal area by 91.2% (p<0.05) versus
      injury alone. PROLI/NO powder was noted to reduce the medial area (40.2% vs
      injury alone, p<0.05), whereas other groups showed no such effect. Three days
      postinjury, each NO treatment group significantly reduced cellular proliferation.
      However, inflammatory markers revealed a distinct pattern: PAN/NO groups
      displayed increased leukocyte infiltration (p<0.05), whereas PROLI/NO groups
      displayed less macrophage infiltration (p<0.05). In conclusion, perivascular
      delivery of diazeniumdiolate NO donors in powder or gel form effectively inhibits
      neointimal hyperplasia. Application of short-acting PROLI/NO powder most
      effectively inhibited neointimal hyperplasia and inflammation and may represent a
      simple, clinically applicable NO-eluting therapy to prevent neointimal
      hyperplasia and restenosis after open vascular interventions.

PMID- 18045550
TI  - Redox regulation of resveratrol-mediated switching of death signal into survival
      signal.
AB  - In this study, we determined the changes in the intracellular redox environment
      of the heart during ischemia and reperfusion and the effects of resveratrol on
      such changes. Because redox regulation by thioredoxin (Trx) plays a crucial role
      in signal transduction and cytoprotection against ROS, the effects of resveratrol
      on the changes in the amounts of thioredoxin were monitored in an attempt to
      determine the role of intracellular thioredoxin in resveratrol-mediated changes
      in intracellular redox environment and its role in resveratrol-mediated
      cardioprotection. Rats were randomly divided into four groups: group I, control
      (rats were gavaged with vehicle only); group II, rats were gavaged with 2.5 mg/kg
      body wt resveratrol per day for 10 days; group III, rats were given resveratrol
      for 10 days, but on the 7th day, they were treated with shRNA against Trx-1;
      group IV, rats were given resveratrol for 10 days, but were injected (iv) with
      cisplatin (1 mg/kg body wt) on days 1, 3, 5, 7, and 9. In concert, two groups of
      mice (Dn-Trx-1) and a corresponding wild-type group were also gavaged with 2.5
      mg/kg body wt resveratrol for 10 days. After 10 days, isolated rat and mouse
      hearts perfused via working mode were made globally ischemic for 30 min followed
      by 2 h of reperfusion. Ischemia/reperfusion developed an infarct size of about
      40% and resulted in about 25% apoptotic cardiomyocytes, which were reduced by
      resveratrol. Cisplatin, but not shRNA-Trx-1, abolished the cardioprotective
      abilities of resveratrol. In the experiments with mouse hearts, similar to rat
      hearts, resveratrol significantly reduced the ischemia/reperfusion-mediated
      increase in infarct size and apoptosis in both groups. MDA formation, a
      presumptive marker for lipid peroxidation, was increased in the I/R group and
      reduced in the resveratrol group, and resveratrol-mediated reduction in MDA
      formation was abolished with cisplatin, but not with shRNA-Trx-1. I/R-induced
      reduction in GSH/GSSH ratio was prevented by resveratrol, and resveratrol
      mediated preservation of GSH/GSSG ratio was reduced by cisplatin, but not by sh
      RNA-Trx-1. RT-PCR revealed an increase in both Trx-1 and Trx-2 transcripts; but
      only Trx-2 protein, not Trx-1 protein, was enhanced with resveratrol by Western
      blot analysis. Electron paramagnetic resonance spectroscopic study revealed that
      resveratrol treatment significantly increased the decay rates of nitroxide
      radicals compared to control hearts, suggesting that resveratrol can switch into
      the reduction state more compared to control heart. Finally, resveratrol
      generated a survival signal by phosphorylation of Akt and increase in induction
      of Bcl-2 expression, which was inhibited by cisplatin, but not by shRNA-Trx-1.
      Taken together, the results of this study indicate that resveratrol provides
      cardioprotection by maintaining intracellular redox environments, and Trx-2 is
      likely to play a role in switching I/R-induced death signal into survival signal.

PMID- 18045551
TI  - The mitochondrial thioredoxin system regulates nitric oxide-induced HIF-1alpha
      protein.
AB  - Hypoxia-inducible factor-1 (HIF-1), consisting of two subunits, HIF-1alpha and
      HIF-1beta, is a key regulator for adaptation to low oxygen availability, i.e.,
      hypoxia. Compared to the constitutively expressed HIF-1beta, HIF-1alpha is
      regulated by hypoxia but also under normoxia (21% O(2)) by several stimuli,
      including nitric oxide (NO). In this study, we present evidence that
      overexpression of mitochondrial-located thioredoxin 2 (Trx2) or thioredoxin
      reductase 2 (TrxR2) attenuated NO-evoked HIF-1alpha accumulation and
      transactivation of HIF-1 in HEK293 cells. In contrast, cytosolic-located
      thioredoxin 1 (Trx1) enhanced HIF-1alpha protein amount and activity under NO
      treatments. Taking into consideration that thioredoxins affect the synthesis of
      HIF-1alpha by altering Akt/mTOR signaling, we herein show that p42/44 mitogen
      activated protein kinase and p70S6 kinase are involved. Moreover, intracellular
      ATP was increased in Trx1-overexpressing cells but reduced in cells
      overexpressing Trx2 or TrxR2, providing thus an understanding of how protein
      synthesis is regulated by thioredoxins.

PMID- 18045553
TI  - Engaging the private sector in global health.

PMID- 18045552
TI  - Protective role of calreticulin in HFE hemochromatosis.
AB  - HFE gene mutations are associated with over 80% of cases of hereditary
      hemochromatosis (HH), an iron-overload disease in which the liver is the most
      frequently affected organ. Research on HFE has traditionally focused on its
      interaction with the transferrin receptor. More recent studies have suggested a
      more complex function for this nonclassical MHC-I protein. The aim of this study
      was to examine how HFE and its two most common mutations affect the expression of
      selected genes in a hepatocyte-like cell line. Gene expression was analyzed in
      HepG2 cells overexpressing wild-type and mutant HFE. The effect of HFE in iron
      import and oxidative stress levels was assessed. Unfolded protein response (UPR)
      activated gene expression was analyzed in peripheral blood mononuclear cells from
      characterized HH patients. C282Y HFE down-regulated hepcidin and enhanced
      calreticulin mRNA expression. Calreticulin levels correlated with intracellular
      iron increase and were associated with protection from oxidative stress. In
      C282Y(+/+) patients calreticulin levels correlated with the expression of the UPR
      marker BiP and showed a negative association with the number of hereditary
      hemochromatosis clinical manifestations. The data show that expression of C282Y
      HFE triggers a stress-protective response in HepG2 cells and suggest a role for
      calreticulin as a modifier of the clinical expression of HH.

PMID- 18045554
TI  - Transmission of influenza A in human beings.

PMID- 18045555
TI  - Transmission of influenza A in human beings.

PMID- 18045556
TI  - Transmission of influenza A in human beings.

PMID- 18045558
TI  - Interest and limits of cohort studies in pregnant women.

PMID- 18045559
TI  - Looking down on disease.

PMID- 18045560
TI  - Human brucellosis.
AB  - Human brucellosis still presents scientists and clinicians with several
      challenges, such as the understanding of pathogenic mechanisms of Brucella spp,
      the identification of markers for disease severity, progression, and treatment
      response, and the development of improved treatment regimens. Molecular studies
      have shed new light on the pathogenesis of Brucella spp, and new technologies
      have permitted the development of diagnostic tools that will be useful in
      developing countries, where brucellosis is still a very common but often
      neglected disease. However, further studies are needed to establish optimum
      treatment regimens and local and international control programmes. This Review
      summarises current knowledge of the pathogenic mechanisms, new diagnostic
      advances, therapeutic options, and the situation of developing countries in
      regard to human brucellosis.

PMID- 18045561
TI  - HIV-associated dyslipidaemia: pathogenesis and treatment.
AB  - Dyslipidaemia, consisting of hypertriglyceridaemia together with depressed
      concentrations of high-density lipoprotein cholesterol and elevated low-density
      lipoprotein cholesterol, is being observed with increasing frequency among HIV
      patients. Pathogenic mechanisms include effects of the virus itself, effects of
      the antiretroviral drugs on key metabolic pathways, and drug-associated adipose
      repartitioning with subsequent development of insulin resistance and associated
      metabolic derangements. Diagnostic methods include a fasting lipoprotein profile
      and assessment of secondary factors. Treatment strategies include non
      pharmacological approaches such as changes to diet and lifestyle, as well as
      switching to a less metabolically active antiretroviral regimen without
      compromising antiretroviral efficacy. Pharmacological treatment may include
      statin drugs, fibrates, niacin, or cholesterol absorption inhibitors, in addition
      to management of comorbidities such as increased global cardiometabolic risk and
      insulin resistance.

PMID- 18045562
TI  - Meningococcal carriage in the African meningitis belt.
AB  - In the African meningitis belt, epidemics of meningococcal disease occur
      periodically, although unpredictably, every few years. These epidemics continue
      to cause havoc but new efforts to control the disease, through the use of
      conjugate vaccines, are being made. Conjugate vaccines are likely to reduce
      meningococcal carriage, thus generating herd immunity, but to understand their
      potential impact we need to know more about the epidemiology of meningococcal
      carriage in Africa. We review published studies of meningococcal carriage in the
      African meningitis belt. A wide range of carriage prevalences has been reported,
      from 3% to over 30%, and the serogroup distribution has been variable. Factors
      influencing carriage include age, contact with a case, and the epidemic/endemic
      situation; however, season and immunisation with polysaccharide vaccine have
      little effect. Since the dynamics of carriage within a population are complex,
      longitudinal carriage studies are of great value; however, few such studies have
      been done. Carefully designed carriage studies are needed to measure and
      interpret the impact of meningococcal group A conjugate vaccines in Africa.

PMID- 18045563
TI  - T-cell regulation by CD4 regulatory T cells during hepatitis B and C virus
      infections: facts and controversies.
AB  - In the past few years, we have witnessed extraordinary advances in the
      understanding of the functions of regulatory T (Treg) cells in immunity against
      pathogens. However, controversy exists over the part that these cells play in
      determining the outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infections, the two main causes of chronic liver inflammation worldwide. Treg
      cell responses may be either beneficial or detrimental to those infected with HBV
      and HCV, by either limiting liver immunopathology or suppressing protective T
      cell responses. We review the latest research on CD4 Treg cells, dissect much of
      the Treg-related HBV and HCV literature, and discuss how new insights in Treg
      immunobiology apply to human and primate models of HBV and HCV infections.
      Moreover, we discuss the limitations of the conclusions drawn from current
      studies on Treg cells, and suggest experimental approaches that can resolve
      current conflicts and improve our understanding of the roles of Treg-cell subsets
      in HBV and HCV infections.

PMID- 18045564
TI  - Infections associated with haemophagocytic syndrome.
AB  - Haemophagocytic syndrome or haemophagocytic lymphohistiocytosis is a rare disease
      that is often fatal despite treatment. Haemophagocytic syndrome is caused by a
      dysregulation in natural killer T-cell function, resulting in activation and
      proliferation of lymphocytes or histiocytes with uncontrolled haemophagocytosis
      and cytokine overproduction. The syndrome is characterised by fever,
      hepatosplenomegaly, cytopenias, liver dysfunction, and hyperferritinaemia.
      Haemophagocytic syndrome can be either primary, with a genetic aetiology, or
      secondary, associated with malignancies, autoimmune diseases, or infections.
      Infections associated with haemophagocytic syndrome are most frequently caused by
      viruses, particularly Epstein-Barr virus (EBV). We present a case of EBV
      associated haemophagocytic syndrome in a young adult with no known
      immunosuppression. We briefly review haemophagocytic syndrome and then discuss
      its associated infections, particularly EBV and other herpes viruses, HIV,
      influenza, parvovirus, and hepatitis viruses, as well as bacterial, fungal, and
      parasitic organisms.

PMID- 18045565
TI  - Factors associated with undiagnosed open-angle glaucoma: the Thessaloniki Eye
      Study.
AB  - PURPOSE: To identify factors associated with undiagnosed open-angle glaucoma
      (OAG), primary open-angle glaucoma (POAG), and pseudoexfoliative glaucoma (PEXG)
      in an elderly population in Thessaloniki, Greece. DESIGN: Cross-sectional
      population-based study. METHODS: Randomly selected subjects > or =60 years (n =
      2,554) participated in the study. Subjects were classified as having POAG or PEXG
      according to specific criteria and using a two-scale definition of glaucoma.
      Undiagnosed glaucoma was defined as absence of either prior diagnosis of glaucoma
      or ocular hypertension or prior medical treatment for glaucoma or prior glaucoma
      surgery. Logistic regression analyses were performed with age, gender, family
      history of glaucoma, history of cataract surgery, visual acuity, vertical cup-to
      disk (C/D) ratio, intraocular pressure, Advanced Glaucoma Intervention Study
      visual field score, time since last eye doctor visit, and type of OAG as
      covariates. RESULTS: The prevalence of undiagnosed glaucoma was 57.1% (56/98) for
      POAG, significantly higher than the prevalence of 34.9% (15/43) for PEXG (P =
      .017). POAG patients presented three to four times increased risk to be
      undiagnosed compared with PEXG patients (P = .02 and P = .04, respectively).
      Patients with OAG who had not visited an ophthalmologist during the last year had
      six times an increased risk to be undiagnosed (P = .003). In POAG, smaller
      vertical C/D ratio was statistically significantly associated with an increased
      risk to be undiagnosed (P = .008). CONCLUSIONS: Lack of regular visits to an
      ophthalmologist was a major factor for undiagnosed OAG. POAG was more likely to
      be undiagnosed than PEXG. Since C/D ratio was associated with undiagnosed POAG,
      standardized protocols involving thorough evaluation of the optic disk are
      recommended for ophthalmologists.

PMID- 18045566
TI  - Foveal photoreceptor layer in eyes with persistent cystoid macular edema
      associated with branch retinal vein occlusion.
AB  - PURPOSE: To study the correlation of visual acuity and the foveal photoreceptor
      layer in eyes with persistent cystoid macular edema associated with branch
      retinal vein occlusion (BRVO). DESIGN: Retrospective chart review. METHODS: We
      studied retrospectively the medical records of 42 eyes of 42 patients with
      persistent cystoid macular edema secondary to BRVO, eyes in which the foveal
      thickness was greater than 250 microm at final examination. On the vertical image
      obtained by optical coherence tomography at the final examination, we measured
      thickness of the foveal photoreceptor layer that was beneath the foveal cystoid
      spaces. We also assessed status of the junction between inner and outer segments
      of the photoreceptors (IS/OS) in the fovea. RESULTS: The photoreceptor layer
      beneath the foveal cystoid spaces was detected as a distinct layer with thickness
      varying between 33 microm and 124 microm (mean, 71.1 +/- 26.8 microm). Final
      visual acuity showed no correlation with total foveal thickness (r = 0.336, P =
      .092). However, it did show a close correlation with thickness of the foveal
      photoreceptor layer (r = -0.571, P < .0001). Of the 42 eyes, 15 showed a
      continuous IS/OS line in the fovea. Visual acuity in these eyes with a continuous
      IS/OS line in the fovea was significantly better than that in eyes with a
      discontinuous or interrupted IS/OS line (P < .0001). CONCLUSIONS: Both the
      thickness and the integrity of the foveal photoreceptor layer are associated with
      visual function in eyes with persistent cystoid macular edema associated with
      BRVO.

PMID- 18045567
TI  - Defining real change in prism-cover test measurements.
AB  - PURPOSE: To describe the interobserver test-retest variability of both
      simultaneous prism and cover testing (SPCT) and alternate prism and cover testing
      (APCT) in horizontal deviations, and to calculate 95% limits of agreement that
      might be used to define real change. DESIGN: Prospective cohort study. METHODS:
      Twenty-three patients with sixth nerve palsy and three controls were
      independently examined by two experienced strabismus surgeons. SPCT and APCT were
      performed at distance and near fixation. Test-retest variability and agreement
      between tests were evaluated using Bland-Altman plots and 95% limits of agreement
      were calculated. RESULTS: For SPCT, the 95% limits of agreement half-widths were
      6.3 prism diopters (pd) at distance fixation and 6.9 pd at near. For APCT, the
      95% limits of agreement half-widths were 10.2 pd at distance and 9.2 pd at near.
      CONCLUSIONS: Based on 95% limits of agreement half-widths between two examiners,
      a change in strabismus measurements of less than 10 pd may be attributable to
      test-retest variability. Changes of 10 pd or more are likely to represent real
      change and might be used as the threshold for management decisions.

PMID- 18045568
TI  - The epidemiology of retinal reticular drusen.
AB  - PURPOSE: To describe the prevalence and 15-year cumulative incidence of and risk
      factors for reticular drusen. DESIGN: Population-based prospective study.
      METHODS: Four thousand nine hundred and twenty-six persons, 43 to 86 years of
      age, were included between 1988 and 1990, of whom 3,684, 2,764, and 2,119
      participated in five-, 10-, and 15-year follow-up examinations, respectively, in
      Beaver Dam, Wisconsin. Main outcome measures included prevalence and 15-year
      incidence of reticular drusen determined by grading stereoscopic color fundus
      photographs. RESULTS: The prevalence at baseline and the 15-year cumulative
      incidence in either eye of reticular drusen was 0.7% and 3.0%, respectively. The
      15-year incidence of reticular drusen varied with age from 0.4% in those 43 to 54
      years of age to 6.6% in those 75 years or older at baseline (P < .001). In a
      multivariate model, while controlling for age, risk factors statistically
      significantly associated with increased risk of incident reticular drusen
      included: being female (odds ratio [OR], 2.8), current smoking (OR vs never,
      1.9), less education (OR per category, 1.7), B-vitamin complex use (OR vs none,
      2.5), single vitamin B (OR vs none, 2.9), history of steroid eye drops use (OR,
      5.9), glaucoma (OR, 2.8), and more severe drusen type (e.g., soft indistinct
      drusen; OR, 1.4), whereas diabetes (OR, 0.1) at baseline was associated with
      decreased risk. Right eyes with reticular drusen at baseline had higher
      cumulative incidence of geographic atrophy (21% vs 9%) and exudative age-related
      macular degeneration [AMD] (20% vs 10%) compared with eyes with soft indistinct
      drusen. CONCLUSIONS: This population-based study documents the long-term
      cumulative incidence of reticular drusen and its risk factors and shows its
      association with a high risk of incident late AMD.

PMID- 18045569
TI  - Glaucoma probability score vs Moorfields classification in normal, ocular
      hypertensive, and glaucomatous eyes.
AB  - PURPOSE: To evaluate the Heidelberg Retina Tomograph III (HRT III) glaucoma
      probability score in differentiating normal from pathologic eyes and to compare
      the glaucoma probability score with Moorfields regression analysis (MRA). DESIGN:
      Prospective cross-sectional study. METHODS: Fifty-nine normal, 40 hypertensive,
      and 83 glaucomatous eyes were examined with Swedish interactive threshold
      algorithm standard 24-2 visual fields and HRT III. Sensitivity and specificity
      were evaluated using global and sectorial glaucoma probability score and MRA
      compared with damage in visual fields. Areas under receiver operating
      characteristic (ROC) curves were evaluated. Agreement between MRA and glaucoma
      probability score was calculated using the kappa coefficient. Glaucoma
      probability score was considered to be displaced when a symbol was outside and
      the opposite symbol was inside the optic disk. RESULTS: MRA sensitivity and
      specificity were 39.8% and 93.2% (most specific criteria) and 68.7% and 83.1%
      (least specific criteria), respectively. Glaucoma probability score sensitivity
      and specificity were 71.1% and 69.5% (most specific criteria) and 85.5% and 54.2%
      (least specific criteria), respectively. Visual field parameters were related to
      the global (P = .001) and sectorial (P < .05) glaucoma probability score. A
      displaced glaucoma probability score was found in 35 eyes, but with unchanged
      glaucoma probability score sensitivity and specificity. Areas under the ROC
      curves of glaucoma probability score was 0.77. The kappa coefficient was 0.34.
      CONCLUSIONS: Glaucoma probability score analysis tends to be more sensitive but
      less specific than MRA. Glaucoma probability score did not differentiate normal
      and hypertensives eyes. When displaced, glaucoma probability score sensitivity
      and specificity were unchanged. MRA and glaucoma probability score agreement was
      low. Glaucoma probability score is advantageous over MRA in early-stage glaucoma.

PMID- 18045570
TI  - [Growth hormone deficiency and pituitary stalk interruption in Fanconi anemia].
AB  - Fanconi anemia is a rare disorder inherited by recessive autosomic transmission
      belonging to the group of chromosomal instability syndromes. It is characterized
      by progressively developing medullary aplasia, various congenital malformations
      and especially a high risk of cancer, particularly acute myeloblastic leukemia
      and certain solid tumors. The association is quite common in patients with
      endocrine disease which constitutes an additional factor of morbidity and must be
      diagnosed and treated. We report a case of Fanconi anemia revealed by severe
      delay in statural growth and primary amenorrhea with a 21-year-old girl. The
      diagnosis was suggested by asymptomatic pancytopenia caused by a medullary
      hypoplasia and confirmed by a cytogenetic investigation using cross-linking
      agents that showed a large number of chromosomal breaks. Hormonal exploration
      revealed hypopituitarism with complete growth hormone (GH) deficiency and
      hypogonadotrophic hypogonadism caused by interruption of the pituitary stalk. The
      aim of this case report is to illustrate the importance of early exploration of
      retarded growth which, in some patients, can reveal potentially serious, and
      treatable, disease.

PMID- 18045571
TI  - Thermal insulation and clothing area factors of typical Arabian Gulf clothing
      ensembles for males and females: measurements using thermal manikins.
AB  - The thermal insulation of clothing is one of the most important parameters used
      in the thermal comfort model adopted by the International Standards Organisation
      (ISO) [BS EN ISO 7730, 2005. Ergonomics of the thermal environment. Analytical
      determination and interpretation of thermal comfort using calculation of the PMV
      and PPD indices and local thermal comfort criteria. International Standardisation
      Organisation, Geneva.] and by ASHRAE [ASHRAE Handbook, 2005. Fundamentals.
      Chapter 8. American Society of Heating Refrigeration and Air-conditioning
      Engineers, Inc., 1791 Tullie Circle N.E., Atlanta, GA.]. To date, thermal
      insulation values of mainly Western clothing have been published with only
      minimal data being available for non-Western clothing. Thus, the objective of the
      present study is to measure and present the thermal insulation (clo) values of a
      number of Arabian Gulf garments as worn by males and females. The clothing
      ensembles and garments of Arabian Gulf males and females presented in this study
      are representative of those typically worn in the region during both summer and
      winter seasons. Measurements of total thermal insulation values (clo) were
      obtained using a male and a female shape thermal manikin in accordance with the
      definition of insulation as given in ISO 9920. In addition, the clothing area
      factors (f cl) determined in two different ways were compared. The first method
      used a photographic technique and the second a regression equation as proposed in
      ISO 9920, based on the insulation values of Arabian Gulf male and female garments
      and ensembles as they were determined in this study. In addition, fibre content,
      descriptions and weights of Arabian Gulf clothing have been recorded and
      tabulated in this study. The findings of this study are presented as additions to
      the existing knowledge base of clothing insulation, and provide for the first
      time data for Arabian Gulf clothing. The analysis showed that for these non
      Western clothing designs, the most widely used regression calculation of f cl is
      not valid. However, despite the very large errors in f cl made with the
      regression method, the errors this causes in the intrinsic clothing insulation
      value, I cl, are limited.

PMID- 18045572
TI  - Prostaglandin E2 inhibits mineralization and enhances matrix metalloproteinase-13
      in mature cementoblasts mainly via the EP4 pathway.
AB  - OBJECTIVES: Prostaglandin E(2) (PGE(2)) is an important factor in the
      pathogenesis of periodontal disease because of bone resorbing activity and
      association with attachment loss. PGE(2) and PGE receptor subtypes (EPs) play an
      important role in modulating bone metabolism via osteoblasts. However, little is
      known about the effects of PGE(2) on cementoblasts. The aims of this study were
      to determine the expression of EPs in mature cementoblasts, and to examine the
      effect of PGE(2) and EPs on their cellular function. DESIGN: Expression of EPs in
      immortalized mouse cementoblasts (OCCM-30 cells), which were characterized as
      mature cementoblasts, was determined using reverse transcriptase polymerase chain
      reaction (RT-PCR). The effects of PGE(2) and EP agonists on mineralization were
      examined by studying nodule formation with alizarin red S staining. Alkaline
      phosphatase (ALP) activity with PGE(2) and EP4 agonist was examined using the
      Bessey-Lowry enzymologic method. Effects of the PGE(2)-EP4 pathway on expression
      levels of osteocalcin (OCN) and matrix metalloproteinase-13 (MMP-13) mRNA were
      examined using real-time RT-PCR. RESULTS: OCCM-30 cells expressed EP1, EP2, EP3
      and EP4 mRNA. PGE(2) and EP4 agonist led to downregulation of mineralized nodule
      formation and ALP activity in OCCM-30 cells. OCN mRNA expression was suppressed
      and MMP-13 mRNA expression was stimulated via the PGE(2)-EP4 pathway in OCCM-30
      cells. CONCLUSIONS: Cementoblasts may downregulate their mineralization ability
      and upregulate MMP-13 production through the PGE(2)-EP4 pathway, and may
      contribute to destruction of connective tissue attachment under inflammatory
      conditions.

PMID- 18045573
TI  - Identification of a cis-acting element of human dihydrofolate reductase mRNA.
AB  - Human dihydrofolate reductase (DHFR) is a critical target in cancer chemotherapy.
      Previous studies showed that an 82-nt RNA fragment within the DHFR mRNA protein
      coding region functions as a DHFR cis-acting response element. In this study, we
      further investigated the key elements contained within this sequence that are
      required for the DHFR mRNA-DHFR protein interaction. Using enzymatic foot
      printing assays and RNA-binding experiments, we isolated a 27-nt sequence
      (DHFR27, corresponding to nts 407-433), which bound with high affinity and
      specificity to human DHFR to form a ribonucleoprotein complex. In vivo transient
      transfection experiments using a luciferase reporter system revealed that DHFR27
      RNA could repress the luciferase expression in a DHFR-dependent manner when
      placed upstream of luciferase mRNA. This work provides new insights into the
      essential molecular elements that mediate RNA-protein interactions.

PMID- 18045574
TI  - Alpha anomer of 5-aza-2'-deoxycytidine down-regulates hTERT mRNA expression in
      human leukemia HL-60 cells.
AB  - DNA methylation inhibitors are being extensively studied as potential anticancer
      agents. In the present study, we compared the capability of alpha anomer of 5-aza
      2'-deoxycytidine (alpha-5-azadCyd) to induce down-regulation of hTERT expression
      in HL-60 cells with other nucleoside analogs that act as DNA methylation
      inhibitors: beta-5-azadCyd (decitabine), (S)-9-(2,3-dihydroxypropyl)adenine [(S)
      DHPA], isobutyl ester of (R,S)-3-(adenin-9-yl)-2-hydroxypropanoic acid [(R,S)
      AHPA-ibu] and prospective DNA methylation inhibitors (S)-1-[3-hydroxy-2
      (phosphonomethoxy)propyl]-5-azacytosine [(S)-HPMPazaC] and 5-fluoro-zebularine (F
      PymRf). Exposure to alpha-5-azadCyd induced the down-regulation of hTERT
      expression in low micromolar concentrations (0.05-50 microM). A more cytotoxic
      beta anomer caused a transient up-regulation of hTERT and a subsequent reduction
      in hTERT mRNA levels at concentrations more than 10 times below its GIC50 value.
      In this respect, (S)-DHPA and (R,S)-AHPA-ibu were less efficient, since a similar
      effect was achieved at concentrations above their GIC(50). In contrast, F-PymRf
      treatment resulted in up to a three-fold induction of hTERT expression within a
      broad range of concentrations. In all cases, the down-regulation of hTERT
      expression was concentration-dependent. The correlation was found between c-myc
      overexpression and transiently elevated hTERT expression after treatment with all
      tested compounds except for alpha-5-azadCyd and (S)-HPMPazaC. Although the
      primary task of hypomethylating agents in anticancer therapy lies in reactivation
      of silenced tumour-suppressor genes, the inhibition of hTERT expression might
      also be a fruitful clinical effect of this approach.

PMID- 18045575
TI  - Vascular integrin immunoreactivity is selectively lost on capillaries during rat
      focal cerebral ischemia and reperfusion.
AB  - The alpha1-integrin cell adhesion molecules, the principal endothelial receptors
      for basal lamina (BL) components disappear during transient ischemia. The current
      study investigated the localization of integrins, the time dependency and vessel
      size selectivity in the normal rat brain before and after 3 h of cerebral
      ischemia (I3) and reperfusion (R). Additionally we looked for a correlation to
      the amount of extravasation and hemorrhage. In the normal brain, there was a
      clear immunoreactivity for the alpha1, alpha6, and beta1 integrins on the
      endothelial perivascular cells. After I3 followed by variable reperfusion
      intervals of 0, 9, and 24 h (R0, R9 and R24; respectively), the number of vessels
      and staining intensity indicating immunoreactivity in the ischemic area were
      compared with the contralateral side. The number of the beta1-immunoreactive
      capillaries was steadily decreasing with the reperfusion time: -12+/-5%, -15+/-7%
      and -43+/-8% at I3R0, I3R9 and I3R24 (all p<0.05). The beta1-staining intensity
      decreased homogeneously to -21% at I3R24 (p<0.05). Vascular staining for alpha1
      was affected similarly. Interestingly, the alpha6-positive arterioles/venules
      were also reduced by -21% at I3R24 (p<0.05) in a diameter-selective way on
      vessels with diameters larger than 15 mum. The correlated break-down of the blood
      brain-barrier was demonstrated by the significant rise of the extravasation of
      BSA from the perfusion solution as well as the increased hemorrhage after MCAO/R
      (hemoglobin: 103+/-4% versus 330+/-17%; BSA 101+/-3% versus 132+/-9% in I0R0 and
      I3R24, respectively). The prominent capillary vulnerability contributes
      significantly to the impairment of the microvascular integrity and after ischemia
      and reperfusion.

PMID- 18045576
TI  - X-ray crystallographic study of several 2'-deoxy-beta-D-ribonucleosides with 1
      deazapurine-derived aglycones.
AB  - The 2'-deoxy-beta-D-ribonucleosides of 1,3-deazapurine (benzimidazole (1)), 1
      deazapurine (both 1H-imidazo[4,5-b]pyridine (2) and 3H-imidazo[4,5-b]pyridine
      (3)), and 6-benzoylamino-1-deazapurine (7-benzoylamino-3H-imidazo[4,5-b]pyridine
      (4)) have been prepared and structurally characterized by X-ray crystallography.
      Especially compounds 1-3 can serve as artificial nucleosides that may substitute
      2'-deoxy adenosine because they lack the exocyclic amino group and one or two of
      the endocyclic nitrogen atoms and hence have a much smaller potential to engage
      in hydrogen bonds. In the latter respect, they are candidates for nucleosides in
      metal-ion mediated base pairs. The unit cell of compound 3 contains two
      crystallographically independent molecules. Compound 4 was crystallized from
      methanol and water, respectively, giving rise to two different solvates. Despite
      the closely related aglycones, the sugar conformations in 1-4 are found to be
      highly variable (1: (2)T(1); 2: (3)T(2); 3: (3)E and E(4); 4: (2)E and (2)T(3)).
      The structures reported here confirm that there is no simple correlation between
      the sugar conformation and the character of the nucleoside, and they will
      hopefully contribute to a better understanding of the complex interplay of
      different effects that are in control of the conformational equilibrium.

PMID- 18045577
TI  - Inhibition of acid-catalyzed depolymerization of cellulose with boric acid in non
      aqueous acidic media.
AB  - Boric acid inhibited the acid-catalyzed depolymerization of cellulose in
      sulfolane, a non-aqueous medium, at high temperature. Formation of the
      dehydration products such as levoglucosenone, furfural, and 5-hydroxymethyl
      furfural were also effectively inhibited. Similar inhibition was observed for
      cellooligosaccharides and starch, although the glucosidic bonds in methyl
      glucopyranosides and methyl cellobioside were cleaved to form alpha-d
      glucofuranose cyclic 1,2:3,5-bisborate.

PMID- 18045578
TI  - Preparation of chitosan-nylon-6 blended membranes containing silver ions as
      antibacterial materials.
AB  - Chitosan-nylon-6 blended membranes were prepared by combining solvent evaporation
      and a phase inversion technique, and then used to chelate silver ions. Gram
      positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia
      coli) were used to study the antibacterial properties of the membranes. Fourier
      transform infrared spectroscopy (FTIR) and differential scanning calorimetry
      (DSC) indicated hydrogen-bond interactions between chitosan and nylon-6. From the
      scanning electron microscopy (SEM) pictures, it was observed that with the
      increase of nylon-6 content, the blended membrane gradually became a material
      with porous morphology. After chelating silver ions, the tensile strength of the
      membranes increased. The antibacterial activity with the variation of chitosan
      content, the pH value and the concentration of the silver nitrate solution used
      to prepare Ag(+)-loaded membranes were investigated systematically. The results
      indicated that the chitosan-nylon-6 blended membranes with Ag(+) were
      antibacterial to both Gram-positive bacteria and Gram-negative bacteria. The
      antibacterial activity improved with the increased chitosan content due to the
      larger amount of silver ions loaded. The antibacterial property of the chitosan
      nylon-6 blended membranes could be primarily attributed to the content of
      chitosan and silver ions as well as the surface morphology of the membranes.

PMID- 18045579
TI  - Methanolysis of ethyl esters of N-acetyl amino acids catalyzed by
      cyclosophoraoses isolated from Rhizobium meliloti.
AB  - Methanolysis of four ethyl esters, N-acetyl-L-phenylalanine ethyl ester, N-acetyl
      l-tyrosine ethyl ester, N-acetyl-l-tryptophan ethyl ester, and ethyl
      phenylacetate was catalyzed by a mixture of microbial cyclooligosaccharides
      termed cyclosophoraoses isolated from Rhizobium meliloti. Cyclosophoraoses
      [cyclic-(1-->2)-beta-d-glucans, collectively 'Cys'] are a mixture of large-ring
      molecules consisting of various numbers of glucose residues (17-27) linked by
      beta-(1-->2)-glycosidic bonds. Cys as a catalytic carbohydrate enhanced the
      methanolysis about 233-fold for N-acetyl-L-tyrosine ethyl ester in comparison
      with a control. The effect of dry organic solvents on the methanolysis of N
      acetyl-L-tyrosine ethyl ester was investigated by high-performance liquid
      chromatography (HPLC), and it was found that the rate enhancement correlated
      closely with the hydrophobicity of the solvent.

PMID- 18045580
TI  - Lipopolysaccharide induced expression of pentraxin 3 in human neutrophils and
      monocyte-derived macrophages.
AB  - Pentraxin 3 (PTX3) is a prototype protein of long pentraxin. PTX3 is produced by
      various cells, such as monocytes/macrophages (Mphis) in response to
      lipopolysaccharide (LPS) and proinflammatory signals. We performed
      immunoblotting, immunohistochemical staining, reverse transcriptase-polymerase
      chain reaction (RT-PCR), quantitative real-time PCR and enzyme-linked
      immunosorbent assay (ELISA) of PTX3 in human monocyte-derived Mphis and
      neutrophils. PTX3 expression was observed in the cytoplasm of both GM-CSF induced
      monocyte-derived Mphi (GM-Mphi) and M-CSF induced monocyte-derived Mphi (M-Mphi).
      PTX3 level in both Mphis was up-regulated at 24 h after LPS stimulation.
      Moreover, we confirmed PTX3 expression in freshly isolated neutrophils, and PTX3
      level was distinctly up-regulated at 6 and 24 h after LPS stimulation. These
      findings suggested that PTX3 expression, not only in Mphis, but also in
      neutrophils, may reflect the role of PTX3 in inflammation. We believe that PTX3
      can contribute as a diagnostic tool to evaluate inflammation at peripheral sites.

PMID- 18045581
TI  - Hepatoprotective effects of Solanum nigrum Linn extract against CCl(4)-induced
      oxidative damage in rats.
AB  - Solanum nigrum L. (SN) is an herbal plant that has been used as hepatoprotective
      and anti-inflammation agent in Chinese medicine. In this study, the protective
      effects of water extract of SN (SNE) against liver damage were evaluated in
      carbon tetrachloride (CCl4)-induced chronic hepatotoxicity in rats. Sprague
      Dawley (SD) rats were orally fed with SNE (0.2, 0.5, and 1.0 g kg(-1) bw) along
      with administration of CCl4 (20% CCl4/corn oil; 0.5 mL kg(-1) bw) for 6 weeks.
      The results showed that the treatment of SNE significantly lowered the CCl4
      induced serum levels of hepatic enzyme markers (GOT, GPT, ALP, and total
      bilirubin), superoxide and hydroxyl radical. The hepatic content of GSH, and
      activities and expressions of SOD, GST Al, and GST Mu that were reduced by CCl4
      were brought back to control levels by the supplement of SNE. Liver
      histopathology showed that SNE reduced the incidence of liver lesions including
      hepatic cells cloudy swelling, lymphocytes infiltration, hepatic necrosis, and
      fibrous connective tissue proliferation induced by CCl4 in rats. Therefore, the
      results of this study suggest that SNE could protect liver against the CCl4
      induced oxidative damage in rats, and this hepatoprotective effect might be
      contributed to its modulation on detoxification enzymes and its antioxidant and
      free radical scavenger effects.

PMID- 18045582
TI  - A computer-aided MFCC-based HMM system for automatic auscultation.
AB  - Auscultation, the act of listening to the sounds of internal organs, is a
      valuable medical diagnostic tool. Auscultation methods provide the information
      about a vast variety of internal body sounds originated by various organs such as
      heart, lungs, bowel, vascular disorders, etc. In this study, a cardiac sound
      registration system has been designed incorporating functions such as heart
      signals segmentation, classification and characterization for automated
      identification and ease of interpretation by the users. Considering a synergy
      with the domain of speech analysis, the authors introduced Mel-frequency cepstral
      coefficient (MFCC) to extract representative features and develop hidden Markov
      model (HMM) for signal classification. This system was applied to 1381 data sets
      of real and simulated, normal and abnormal domains. Classification rates for
      normal and abnormal heart sounds were found to be 95.7% for continuous murmurs,
      96.25% for systolic murmurs and 90% for diastolic murmurs by a probabilistic
      comparison approach. This implies a high potential for the system as a diagnostic
      aid for primary health-care sectors.

PMID- 18045584
TI  - Relationship between intracellular ice formation in oocytes of the mouse and
      Xenopus and the physical state of the external medium--a revisit.
AB  - We have previously reported that intracellular ice formation (IIF) in mouse
      oocytes suspended in glycerol/PBS solutions or ethylene glycol (EG)/PBS solutions
      and rapidly cooled to -50 degrees C or below occurs at temperatures where a
      critical fraction of the external water remains unfrozen [P. Mazur, S. Seki, I.L.
      Pinn, F.W. Kleinhans, K. Edashige, Extra- and intracellular ice formation in
      mouse oocytes, Cryobiology 51 (2005) 29-53; P. Mazur, I.L. Pinn, F.W. Kleinhans,
      The temperature of intracellular ice formation in mouse oocytes vs. the unfrozen
      fraction at that temperature, Cryobiology 54 (2007) 223-233]. For mouse oocytes
      in PBS or glycerol/PBS that fraction is 0.06; for oocytes in EG that fraction was
      calculated to be 0.13, more than double. The fractions unfrozen are computed from
      ternary phase diagrams. In the previous publication, we used the EG data of Woods
      et al. [E.J. Woods, M.A.J. Zieger, D.Y. Gao, J.K. Critser, Equations for
      obtaining melting points for the ternary system ethylene glycol/sodium
      chloride/Water and their application to cryopreservation., Cryobiology 38 (1999)
      403-407]. Since then, we have determined that ternary phase diagrams for
      EG/NaCl/water synthesized by summing binary phase data for EG/water NaCl/water
      gives substantially different curves, which seem more realistic [F.W. Kleinhans,
      P. Mazur, Comparison of actual vs. synthesized ternary phase diagrams for solutes
      of cryobiological interest, Cryobiology 54 (2007) 212-222]. Unfrozen fractions at
      the temperatures of IIF computed from these synthesized phase diagrams are about
      half of those calculated from the Woods et al. data, and are in close agreement
      with the computations for glycerol; i.e., IIF occurs when about 92-94% of the
      external water is frozen. A parallel paper was published by Guenther et al. [J.F.
      Guenther, S. Seki, F.W. Kleinhans, K. Edashige, D.M. Roberts, P. Mazur, Extra-and
      intra-cellular ice formation in Stage I and II Xenopus laevis oocytes,
      Cryobiology 52 (2006) 401-416] on IIF in oocytes of the frog Xenopus. It too
      examined whether the temperatures of IIF were related to the unfrozen fractions
      at those temperatures. It also used the Woods et al. ternary phase data to
      calculate the unfrozen fractions for EG solutions. As reported here, once again
      the values of these unfrozen fractions are substantially different from those
      calculated using synthesized phase diagrams. With the latter, the unfrozen
      fractions at IIF become very similar for EG and glycerol.

PMID- 18045585
TI  - Survival of Pacific oyster, Crassostrea gigas, oocytes in relation to
      intracellular ice formation.
AB  - The effect of IIF in Pacific oyster oocytes was studied using cryo and
      transmission electron microscopy (TEM). The viability of oocytes at each step of
      a published cryopreservation protocol was assessed in an initial experiment. Two
      major viability losses were identified; one when oocytes were cooled to -35
      degrees C and the other when oocytes were plunged in liquid nitrogen. Although
      the cryomicroscope showed no evidence of IIF in oocytes cooled with this
      protocol, TEM revealed that these oocytes contained ice crystals and were at two
      developmental stages when frozen, prophase and metaphase I. To reduce IIF, the
      effect of seven cooling programmes involving cooling to -35 or -60 degrees C at
      0.1 or 0.3 degrees C min(-1) and holding for 0 or 30 min at -35 or -60 degrees C
      was evaluated on post-thaw fertilization rate of oocytes. Regardless of the
      cooling rate or holding time, the fertilization rate of oocytes cooled to -60
      degrees C was significantly lower than that of oocytes cooled to -35 degrees C.
      The overall results indicated that observations of IIF obtained from
      cryomicroscopy are limited to detection of larger amounts of ice within the
      cells. Although the amount of cellular ice may have been reduced by one of the
      programmes, fertilization was reduced significantly; suggesting that there is no
      correlation between the presence of intracellular ice and post-thaw fertilization
      rate. Therefore, oyster oocytes may be more susceptible to the effect of high
      solute concentrations and cell shrinkage than intracellular ice under the studied
      conditions.

PMID- 18045586
TI  - Striking association between urinary cadmium level and albuminuria among Torres
      Strait Islander people with diabetes.
AB  - OBJECTIVES: Indigenous people of the Torres Strait (Australia) have greater
      potential for cadmium exposure and renal damage than other Australians due to
      high cadmium in some traditional seafood and a high prevalence of Type 2
      diabetes, hypertension, smoking, and obesity. This study explored associations
      between albuminuria and an index of cadmium exposure (urinary cadmium excretion)
      in the presence and absence of Type 2 diabetes. RESEARCH DESIGN AND METHODS: Two
      population-based, cross-sectional studies were undertaken in the Torres Strait to
      obtain data on body mass index (BMI), blood pressure, chronic disease, smoking,
      urinary cadmium, and albumin creatinine ratio (ACR). RESULTS: Age- and BMI
      adjusted urinary cadmium levels were significantly higher (p<0.01) among people
      with diabetes and albuminuria (n=22, geometric mean (GM) 1.91 microg Cd/g
      creatinine) compared to those with diabetes and normal ACR (n=21, GM 0.74 microg
      Cd/g creatinine). Urinary cadmium was also strongly associated (p<0.001) with ACR
      among people with diabetes in regression models and remained significant after
      controlling for age, sex, BMI, smoking status, and hypertension (or continuous
      systolic and diastolic measurements). CONCLUSIONS: While the study has
      methodological limitations and the nature of the association is unclear, the
      striking dose-dependent links between markers of cadmium exposure and of Type 2
      diabetic nephropathy highlight the need for further definitive research on the
      health effects of cadmium in the presence of diabetes.

PMID- 18045587
TI  - Electrophysiological evidence for impairment of contrast sensitivity in mercury
      vapor occupational intoxication.
AB  - Contrast sensitivity (CS) was evaluated in 41 former workers from a lamp
      manufacturing plant who were on disability retirement due to exposure to mercury
      and 14 age-matched controls. The CS was measured monocularly using the sweep
      visual evoked potential (sVEP) paradigm at 6 spatial frequencies (0.2, 0.8, 2.0,
      4.0, 15.0, and 30 cpd). Statistical difference (p<0.05) was found between the
      controls and the patient right and left eyes for 2.0 and 4.0 cpd. According the
      results in those spatial frequencies the eyes were classified in best and worst.
      Statistical differences were found between the controls and the best eyes for 2.0
      and 4.0 cpd and for 0.8, 2.0, and 4.0 cpd for their worst eyes. No correlation
      was found between CS results and the time of exposure (mean=8.9 yr+/-4.1), time
      away from the mercury source (mean=6.0 yr+/-3.9), urinary mercury level at the
      time of work (mean=40.6 microg/g+/-36.3) or with the mercury level at the CS
      measurement time (mean=1.6 microg/g+/-1.1). We show the first evidence of a
      permanent impairment in CS measured objectively with the sVEP. Our data
      complement the previous psychophysical works reporting a diffuse impairment in
      the CS function showing a CS reduction in the low to middle spatial frequencies.
      In conclusion, non-reversible CS impairment was found in occupational exposure to
      mercury vapor. We suggest that CS measurement should be included in studies of
      the mercury effects of occupational exposure.

PMID- 18045588
TI  - Nicorandil enhances the effect of endothelial nitric oxide under hypoxia
      reoxygenation: role of the KATP channel.
AB  - Nicorandil increased the anti-platelet aggregation activity of endothelial cells
      when endothelial cells were exposed to hypoxia-reoxygenation conditions. However,
      nicorandil (0.1-10 muM) did not inhibit platelet aggregation directly. The
      mechanism by which nicorandil increases the anti-aggregation activity of hypoxia
      reoxygenation treated endothelial cells was investigated. The effect of
      nicorandil was observed even in indomethacin-treated endothelial cells, but the
      effect was eliminated by treating endothelial cells with N(G)-nitro-l-arginine
      methyl ester (L-NAME). This indicates that nicorandil enhances the anti
      aggregation activity of endothelial nitric oxide (NO). Nicorandil did not
      increase the anti-aggregation activity of endothelial NO when endothelial cells
      were pre-treated with superoxide dismutase or 4-(2-aminophenyl)-benzenesulfonyl
      fluoride, an inhibitor of NADPH oxidase. Nicorandil dose-dependently inhibited
      the reactive oxygen species generation induced by an oxidative stress in
      endothelial cells. The effect of nicorandil on anti-aggregation activity was
      abrogated by glibenclamide, an ATP-sensitive potassium (K(ATP)) channel blocker.
      Pinacidil, a K(ATP) channel opener, also enhanced the anti-aggregation activity
      of endothelial NO. This effect was similarly abrogated by glibenclamide. These
      results suggest that nicorandil may inhibit the generation of superoxide (O(2)(
      )) from hypoxia-reoxygenation treated endothelial cells through activation of the
      K(ATP) channel, and that nicorandil may prevent the disappearance of endothelial
      NO by O(2)(-).

PMID- 18045589
TI  - The C-terminus of the gamma 2 chain but not of the beta 3 chain of laminin-332 is
      indirectly but indispensably necessary for integrin-mediated cell reactions.
AB  - Using a recombinant mini-laminin-332, we showed that truncation of the three C
      terminal amino acids of the gamma 2 chain, but not of the C-terminal amino acid
      of the beta 3 chain, completely abolished alpha 3 beta 1 integrin binding and its
      cellular functions, such as attachment and spreading. However, a synthetic
      peptide mimicking the gamma 2 chain C-terminus did not interfere with alpha 3
      beta 1 integrin binding or cell adhesion and spreading on laminin-332 as measured
      by protein interaction assays and electric cell-substrate impedance sensing. Nor
      was the soluble peptide able to restore the loss of integrin-mediated cell
      adhesiveness to mini-laminin-332 after deletion of the gamma 2 chain C-terminus.
      These findings spoke against the hypothesis that the gamma 2 chain C-terminus of
      laminin-332 is a part of the alpha 3 beta 1 integrin interaction site. In
      addition, structural studies with electron microscopy showed that truncation of
      the gamma 2 chain C-terminus opened up the compact supradomain structure of LG1-3
      domains. Thus, by inducing or stabilizing an integrin binding-competent
      conformation or array of the LG1-3 domains, the gamma 2 chain C-terminus plays an
      indirect but essential role in laminin-332 recognition by alpha 3 beta 1 integrin
      and, hence, its cellular functions.

PMID- 18045590
TI  - Expression pattern, regulation, and functions of methionine adenosyltransferase
      2beta splicing variants in hepatoma cells.
AB  - BACKGROUND & AIMS: Methionine adenosyltransferase (MAT) catalyzes S
      adenosylmethionine biosynthesis. Two genes (MAT1A and MAT2A) encode for the
      catalytic subunit of MAT, while a third gene (MAT2beta) encodes for a regulatory
      subunit that modulates the activity of MAT2A-encoded isoenzyme. We uncovered
      multiple splicing variants while characterizing its 5'-flanking region. The aims
      of our current study are to examine the expression pattern, regulation, and
      functions of the 2 major variants: V1 and V2. METHODS: Studies were conducted
      using RNA from normal human tissues, resected hepatocellular carcinoma specimens,
      and cell lines. Gene expression, promoter and nuclear binding activities, growth,
      and apoptosis were measured by routine assays. RESULTS: MAT2beta is expressed in
      most but not all tissues, and the 2 variants are differentially expressed. The
      messenger RNA levels of both variants are markedly increased in hepatocellular
      carcinoma. Tumor necrosis factor (TNF)-alpha, which induces MAT2A in HepG2 cells,
      also induced V1 (but not V2) expression. TNF-alpha induced the promoter activity
      of MAT2beta V1, likely via nuclear factor kappaB and activator protein 1. Both
      variants regulate growth, but only V1 regulates apoptosis. Reduced expression of
      V1 led to c-Jun-N-terminal kinase (JNK) activation, apoptosis, and sensitized
      HepG2 cells to TNF-alpha-induced apoptosis, while overexpression of V1 was
      protective. However, blocking JNK1 or JNK2 activation did not prevent apoptosis
      induced by V1 knockdown. V1 (but not V2) knockdown also leads to apoptosis in a
      colon cancer cell line, suggesting these variants play similar roles in many cell
      types. CONCLUSIONS: Different variants of MAT2beta regulate growth and death,
      which broadens their importance in biology.

PMID- 18045592
TI  - Incidence of esophageal adenocarcinoma in patients with Barrett's esophagus and
      high-grade dysplasia: a meta-analysis.
AB  - BACKGROUND: Patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD)
      are at a high risk for developing esophageal adenocarcinoma. However, the
      reported rate of cancer development in patients with HGD who were undergoing
      surveillance has varied among published studies. OBJECTIVE: To determine an
      overall precise estimate of cancer incidence in patients with HGD who were
      undergoing surveillance endoscopy. DESIGN: Systematic review and meta-analysis.
      METHODS: We conducted a systematic search of the published literature and
      selected original articles that examined patients with histologically proven BE
      and HGD, patients who had not undergone endoscopic ablation or surgical therapy,
      patients with 6 months' follow-up, no esophageal cancer at the time of enrollment
      or within 6 months, and studies in which follow-up was reported in person-time.
      Two investigators independently conducted the search and abstraction. MAIN
      OUTCOME MEASUREMENT: The weighted mean event rate was calculated and expressed as
      the weighted incidence rate, and its CIs were calculated. RESULTS: The search
      yielded 4 articles that met the inclusion criteria, and these were analyzed. A
      total of 236 patients with HGD were followed for 1241 patient-years, and
      esophageal adenocarcinoma was reported in 69 patients, providing a crude
      incidence rate of 5.57 per 100 patient-years. The weighted incidence rate was
      6.58 per 100 patient-years (95% CI, 4.97-8.19). LIMITATIONS: A small number of
      studies that met inclusion criteria. CONCLUSIONS: In patients with BE and with
      HGD who were undergoing surveillance, esophageal adenocarcinoma develops in
      approximately 6 per 100 patient-years during the first few years of follow-up.
      These data may better inform physicians and patients in management decisions.

PMID- 18045591
TI  - Epithelial: lamina propria lymphocyte interactions promote epithelial cell
      differentiation.
AB  - BACKGROUND & AIMS: Intestinal lymphoepithelial interactions occur in the
      epithelium and the subepithelial space. We asked whether normal, Crohn's disease
      (CD), or ulcerative colitis (UC) lamina propria lymphocytes (LPL) could promote
      intestinal epithelial cell (IEC) growth and differentiation. METHODS: T84 cells
      were cocultured with isolated LPL. IECs were then lysed and subjected to
      measurement of intestinal alkaline phosphatase (IAP) activity; Western blot
      analysis for MAPK and Akt activation; and real-time polymerase chain reaction to
      assess caudal-related homeoprotein 2 (CDX2) messenger RNA (mRNA) levels. Tissue
      sections were immunostained for evidence of mitogen-activated protein kinase
      (MAPK) and phosphatidylinositol 3-kinase (PI3K) activation, CDX2, and IAP; and
      CDX2 mRNA expression was assessed in human colonic biopsy specimens. RESULTS: IAP
      activity was increased in T84 cells cocultured for 8 days with normal LPL (P <
      .05) and even greater with CD LPL (P < .001). Crypt IECs in active CD mucosa
      expressed IAP ex vivo. Phospho-MAPK (extracellular signal-regulated kinase 1/2,
      p38, and c-Jun-N-terminal kinase) and phospho-Akt were seen as early as 30
      minutes after coculture. MAPK activation was greatest in T84 cells cocultured
      with CD LPL. There was a specific increase in Phospho-p38 MAPK and Phospho-Akt
      staining in the nuclei of crypt IECs in active vs inactive CD, normal mucosa, and
      UC mucosa. CDX2 mRNA expression was increased in CD LPL cocultured T84 cells,
      which did not correlate with CDX2 protein localization ex vivo. CONCLUSIONS:
      There is cross talk between LPL and IECs, which leads to IEC differentiation. The
      differentiation is accelerated in CD mucosa.

PMID- 18045593
TI  - A model for mortality-morbidity conferences in gastroenterology.

PMID- 18045594
TI  - Renewal of and proctoring for endoscopic privileges.

PMID- 18045595
TI  - Subcapsular hepatic hematoma after ERCP.

PMID- 18045596
TI  - Post-conception reproductive competition in cooperatively breeding common
      marmosets.
AB  - Common marmosets are cooperatively breeding monkeys that exhibit high female
      reproductive skew. Subordinate females usually fail to breed as a consequence of
      ovulation suppression and inhibition of sexual behavior, and, even when they do
      breed, typically rear fewer infants than dominants. We evaluated possible
      mechanisms of post-conception reproductive competition by comparing hormonal
      profiles across pregnancy, pregnancy outcomes, infant survivorship, and behavior
      in laboratory-housed families containing one (N=9) or two (N=7) breeding females.
      Breeding females in plurally breeding groups did not exhibit well-defined
      dominance relationships and rarely engaged in escalated aggression with one
      another. No significant differences were found among singly breeding mothers,
      plurally breeding mothers, and plurally breeding daughters in urinary chorionic
      gonadotropin or estradiol sulfate concentrations during pregnancy, fetal
      biparietal diameter, frequency of spontaneous abortion, frequency of stillbirths,
      number of live-born infants per litter, or infant mortality rates. When females
      gave birth while another female in the family was pregnant, however, their
      infants were highly likely to be killed. The perpetrator was definitively
      identified in only one family, in which a pregnant female killed her daughter's
      infant. These results are consistent with observations of free-living common
      marmosets and suggest that breeding females do not regularly influence one
      another's pregnancy outcomes, but that they may commonly kill each other's
      infants, especially during their own pregnancy. Our findings further suggest that
      infanticide by breeding females may have selected for the evolution of
      reproductive restraint in subordinate female marmosets.

PMID- 18045597
TI  - How useful is the appetitive and consummatory distinction for our understanding
      of the neuroendocrine control of sexual behavior?

PMID- 18045598
TI  - The efficacy of negative pressure wound therapy in the management of lower
      extremity trauma: review of clinical evidence.
AB  - A large number of aids have been conceived and introduced into clinical practice
      (nutritional supplements, local dressings, technical innovations) aimed at
      facilitating and optimising wound healing in both acute and chronic wound
      settings. Among these advances, negative pressure wound therapy (NPWT) has been
      introduced during the last 30 years, and has been analysed in over 400
      manuscripts of the English, Russian and German literature. Until very recently,
      vacuum assisted closure (VAC) (KCI, TX, USA) has been the only readily available
      commercial device that provides localised negative pressure to the wound and is
      the predominant agent used to deliver NPWT featured in this review. We conducted
      a comprehensive review of the existing clinical evidence of the English
      literature on the applications of NPWT in the acute setting of trauma and burns
      of the lower extremity. Overall, 16 clinical studies have been evaluated and
      scrutinised as to the safety and the efficacy of this adjunct therapy in the
      specific environment of trauma. Effectiveness was comparable to the standard
      dressing and wound coverage methods. The existing clinical evidence justifies its
      application in lower limb injuries associated with soft tissue trauma.

PMID- 18045599
TI  - Prevalence and current concepts of management of farmyard injuries.
AB  - Farmyard injuries in young adults and the elderly usually result from machinery
      accidents, whereas children tend to be injured by runovers and motor vehicle
      collisions. A variety of farmyard injuries secondary to environmental and human
      factors may cause permanent disability or even death. Common injuries include
      lacerations, hand injuries, amputations, farm animal bites, fractures and
      dislocations. Special considerations should be taken into account when treating
      these injuries, focusing on their noteworthy bacterial load in order to minimise
      the risk of chronic morbidity.

PMID- 18045600
TI  - Immunity, trauma and the elderly.
AB  - It is believed that an uncontrolled or poorly coordinated immune reaction can be
      stimulated by major trauma and be responsible for the development of the multiple
      organ dysfunction syndrome (MODS). The elderly have a reduced ability to mount an
      effective immune reaction with deficiencies involving both humoral and cellular
      aspects of immunity that involve poor function of both the stimulatory and immuno
      suppressive sides of the immune process. However, there is currently no hard
      evidence that the excess mortality after major trauma in the elderly is
      associated with an impaired or excessive immune response. It is possible that
      their poor resistance to infection is important and immune modulated but the
      dominant factor in the excess mortality in the elderly population is probably
      associated with their lack of physiological reserve to respond to a major
      physiological challenge.

PMID- 18045601
TI  - Effect of a lower-dose cetrorelix acetate protocol on in-vitro fertilization
      outcome.
AB  - OBJECTIVE: To determine whether a low initial dosage of cetrorelix acetate could
      prevent a premature luteinizing hormone (LH) surge in women undergoing controlled
      ovarian stimulation. METHOD: Treatment with a recombinant follicle stimulating
      hormone was started on Day 3 of the menstrual cycle, and 0.125 mg of cetrorelix
      was injected daily from Day 5 of the ovarian stimulation until the diameter of
      the dominant follicle reached at least 16 mm. The dosage was then doubled and
      maintained at 0.250 mg/day until the day before the injection of human chorionic
      gonadotropin. RESULT: There was a significant decrease in serum LH concentration
      1 day after doubling the cetrorelix dosage, and the LH concentration remained low
      during the follicular phase. Clinical pregnancy occurred in 18 women (42.8%),
      with 2 intrauterine fetal deaths before the 12th week. CONCLUSION: Increasing the
      cetrorelix dosage from 0.125 to 0.250 mg/day when the follicular size is
      appropriate can prevent a premature LH surge.

PMID- 18045602
TI  - Ophthalmic artery Doppler velocimetry in healthy pregnancy.
AB  - OBJECTIVES: To establish normative data for ophthalmic artery Doppler parameters
      throughout a healthy pregnancy, to investigate the possible correlation between
      these Doppler measurements and gestational age, and to test intraobserver
      variability. METHODS: A prospective cross-sectional study was performed to assess
      various Doppler parameters in 276 healthy women between 20 and 39 weeks of
      gestation. The following measurements were obtained: pulsatility and resistance
      indices (PI, RI), peak systolic velocity (PSV), peak diastolic velocity (PDV),
      end diastolic flow velocity (EDFV), and peak ratio (PR). Quantile regression was
      used to estimate reference values throughout pregnancy and P<0.05 was considered
      significant. The intraclass correlation coefficient (Intra-CC) was used to
      calculate intraobserver variability. RESULTS: The 5th and 95th prediction
      intervals for each gestational age are presented. No significant correlation was
      detected between Doppler indices and gestational age. Intra-CC was excellent
      (0.996). CONCLUSIONS: Reference values were generated for ophthalmic artery
      Doppler measurements, and they did not vary significantly during healthy
      pregnancy.

PMID- 18045603
TI  - Uterine artery embolization for symptomatic uterine fibroids.

PMID- 18045604
TI  - Uterine tumor resembling ovarian sex cord tumors treated by hysteroscopy.

PMID- 18045605
TI  - Calculating the costs of work-based training: the case of NHS Cadet Schemes.
AB  - BACKGROUND: The worldwide shortage of registered nurses [Buchan, J., Calman, L.,
      2004. The Global Shortage of Registered Nurses: An Overview of Issues And
      Actions. International Council of Nurses, Geneva] points to the need for
      initiatives which increase access to the profession, in particular, to those
      sections of the population who traditionally do not enter nursing. This paper
      reports findings on the costs associated with one such initiative, the British
      National Health Service (NHS) Cadet Scheme, designed to provide a mechanism for
      entry into nurse training for young people without conventional academic
      qualifications. The paper illustrates an approach to costing work-based learning
      interventions which offsets the value attributed to trainees' work against their
      training costs. OBJECTIVE: To provide a preliminary evaluation of the cost of the
      NHS Cadet Scheme initiative. DATA SOURCE: Questionnaire survey of the leaders of
      all cadet schemes in England (n=62, 100% response) in December 2002 to collect
      financial information and data on progression of cadets through the scheme, and a
      follow-up questionnaire survey of the same scheme leaders to improve the quality
      of information, which was completed in January 2004 (n=56, 59% response).
      PRINCIPAL FINDINGS: The mean cost of producing a cadet to progress successfully
      through the scheme and onto a pre-registration nursing programme depends
      substantially on the value of their contribution to healthcare work during
      training and the progression rate of students through the scheme. The findings
      from this evaluation suggest that these factors varied very widely across the 62
      schemes. Established schemes have, on average, lower attrition and higher
      progression rates than more recently established schemes. Using these rates, we
      estimate that on maturity, a cadet scheme will progress approximately 60% of
      students into pre-registration nurse training. CONCLUSIONS: As comparative
      information was not available from similar initiatives that provide access to
      nurse training, it was not possible to calculate the cost effectiveness of NHS
      Cadet Schemes. However, this study does show that those cadet schemes which have
      the potential to offer better value for money, are those where the progression
      rates are good and where the practical training of cadets is organised such that
      cadets meet the needs of patients which might otherwise have to be met by non
      professionally qualified staff.

PMID- 18045606
TI  - Beta3 integrin haplotype influences gene regulation and plasma von Willebrand
      factor activity.
AB  - The Leu33Pro polymorphism of the gene encoding beta(3) integrin (ITGB3) is
      associated with acute coronary syndromes and influences platelet aggregation.
      Three common promoter polymorphisms have also been identified. The aims of this
      study were to (1) investigate the influence of the ITGB3 -400C/A, -425A/C and 
      468G/A promoter polymorphisms on reporter gene expression and nuclear protein
      binding and (2) determine genotype and haplotype associations with platelet
      alpha(IIb)beta(3) receptor density. Promoter haplotypes were introduced into an
      ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase
      reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear
      proteins was assessed by electrophoretic mobility shift assay. The association of
      ITGB3 haplotype with platelet alpha(IIb)beta(3) receptor density was determined
      in 223 subjects. Species conserved motifs were identified in the ITGB3 promoter
      in the vicinity of the three polymorphisms. The GAA, GCC, AAC, AAA and ACC
      constructs induced approximately 50% increased luciferase expression relative to
      the GAC construct in both cell types. Haplotype analysis including Leu33Pro
      indicated five common haplotypes; no associations between ITGB3 haplotypes and
      receptor density were found. However, the GCC-Pro33 haplotype was associated with
      significantly higher vWF activity (128.6 [112.1-145.1]%) compared with all other
      haplotypes (107.1 [101.2-113.0]%, p=0.02). In conclusion, the GCC-Pro33 haplotype
      was associated with increased vWF activity but not with platelet
      alpha(IIb)beta(3) receptor density, which may indicate ITGB3 haplotype influences
      endothelial function.

PMID- 18045608
TI  - Temperature-controlled ionic liquid dispersive liquid phase micro-extraction.
AB  - The present study reports a novel, green and environmental benign sample
      enrichment method termed temperature-controlled ionic liquid dispersive liquid
      phase micro-extraction. An ionic liquid [C6MIM][PF6], was used as the extraction
      solvent and pyrethroid pesticides as the model compounds. The ionic liquid was
      dispersed completely into the aqueous solution under the drive of temperature,
      and the analytes will more easily migrate into the ionic liquid phase because of
      the much larger contact area than that of conventional single drop liquid micro
      extraction. Results obtained indicated that this system could be tuned to a great
      extent because ionic liquids can be designable and the method does not suffer
      from the limitations of that in conventional solvent micro-extraction. Analytical
      parameters of the proposed method were investigated and good linear range (1.5
      100 microg L(-1)), detection limits (0.28-0.6 microg L(-1)), and precision (RSD
      of 2.7-9.3%, n=6) was obtained. Good spiked recoveries from six real water
      samples proved that this method was competitive in practical applications.
      Considering the large variety of ionic liquids and the tunable amounts of used
      ionic liquids in different experiments, the proposed method earns many merits and
      will have a wide application perspective in the future.

PMID- 18045607
TI  - Circulating soluble ICAM-1 levels shows linkage to ICAM gene cluster region on
      chromosome 19: the NHLBI Family Heart Study follow-up examination.
AB  - Atherogenesis is a chronic inflammatory process in which intercellular adhesion
      molecule 1 (ICAM-1) plays a critical role. Circulating soluble ICAM-1 (sICAM-1)
      is thought to be the result of cleavage of membrane-bound ICAM-1 and its
      concentration in serum/plasma has been shown to be heritable. Genome-wide linkage
      scans were conducted for quantitative trait loci influencing sICAM-1. Phenotype
      and genetic marker data were available for 2617 white and 531 black individuals
      in the NHLBI Family Heart Study follow-up examination. Heritability for sICAM-1
      was 0.39 in whites and 0.59 in blacks. Significant linkage was observed on
      chromosome 19 (LOD=4.0 at 14cM) in whites near the ICAM gene cluster that
      includes the structural gene for ICAM-1. The T-allele of ICAM-1 SNP rs5491 has
      been strongly associated with the specific sICAM-1 assay we used in our study.
      Through additional genotyping we were able to rule out rs5491 as the cause of the
      linkage finding. This study provides preliminary evidence linking genetic
      variation in the ICAM1 structural gene to circulating sICAM-1 levels.

PMID- 18045609
TI  - Efficient purification and metabolite analysis of radiotracers using high
      performance liquid chromatography and on-line solid-phase extraction.
AB  - This study describes an efficient method using on-line solid-phase extraction
      (SPE) (Oasis HLB) for preparative HPLC purification of short-lived radiotracers
      for positron emission tomography (PET) and for HPLC analysis of radiotracers and
      their metabolites in cell homogenates, plasma and urine samples. The
      radiochemical purity of tracers (fluorine-18 labeled) purified using this method
      (Oasis column) was >99% compared to 90% when no Oasis column was used.
      Radiometabolites of several fluorine-18 and carbon-11-labeled tracers and one
      technetium-99m tracer were quantified in cell homogenates, plasma and urine
      samples. Samples were analyzed using Oasis column and analytical HPLC system
      without prior precipitation of proteins or removal of other biological matrices.
      The metabolites observed for the evaluated tracers were all polar relative to the
      unchanged tracer. The extraction repeatability was found to be good (RSD 2.2%)
      and recoveries of Oasis column/HPLC-injected radioactivity (plasma) were found to
      be high (mean recovery >91%). The same Oasis column was used for several times
      without back pressure build-up or decrease of the HPLC separation
      characteristics.

PMID- 18045610
TI  - Quantitative determination of chlorophenols in leather by pressurized liquid
      extraction and liquid chromatography with diode-array detection.
AB  - Pressurized liquid extraction (PLE) with acetonitrile was used for the recovery
      of chlorophenols (4-chloro-3-methylphenol, 4-chloro-2-methylphenol, 2,4
      dichlorophenol, 2-phenylphenol, 2,4,6-trichlorophenol, 2,3,4,6-tetrachlorophenol
      and pentachlorophenol) present as biocides in leather. After a single cycle PLE
      treatment, solutions underwent pre-concentration by evaporation of the solvent
      under vacuum and clean-up treatment with solid-phase extraction cartridges.
      Quantitative analysis of the target compounds was carried out by liquid
      chromatography with gradient elution and UV spectrophotometric detection at
      variable wavelength for the various analytes in the range 190-240 nm.
      Instrumental detection limits and operative detection limits in the real matrices
      were determined according to the Hubaux-Vos approach and to the US Environmental
      Protection Agency procedures. The detection limits for the seven analytes ranged
      from 10 to 70 microg kg(-1). Linearity was very good in the explored range (10(
      7)-10(-5)M) giving R(2) values from 0.995 to 1.000 for pentachlorophenol and 2,4
      dichlorophenol, respectively. Repeatability was satisfactory, 2-5% for a 1 x 10(
      6)M level of concentration, on five repeated measurements on the sample. Recovery
      yield values with the proposed procedure were determined using spiked samples.
      Overall recovery ranged from 88 to 97%. The method was used for routine analysis
      of real leather samples.

PMID- 18045611
TI  - Identification of prostate cancer antigens by automated high-throughput filter
      immunoscreening.
AB  - There is a need for earlier and more accurate cancer diagnostics as well as new
      targets for cancer immunotherapy. To this end, it is important to identify sets
      of tumour antigens specific for different cancer forms. Several methods that
      identify potential tumour antigens in an arrayed and high-throughput format have
      been developed during the last years of SEREX (serological identification of
      antigens by recombinant expression cloning) related research. Such techniques may
      hold the potential to describe the complete immunogenic part of the cancer
      proteome, also called the cancer immunoproteome. We have developed a powerful
      platform for automated serological high-throughput filter screening of tumour
      cDNA libraries. The screening format of this method is 18,000 single cDNAs
      clones, which is superior to other high-throughput methods described. The output
      is antigens, which are potential diagnostic cancer markers and vaccine targets.
      We present here the results from the screening of a prostate tumour cDNA library
      with autologous patient antibodies. We first demonstrated the feasibility of the
      automated high-throughput filter immunoscreening method by use of the NY-ESO-1sv
      (NY-ESO-1 splice variant) antigen. We then screened 18,000 cDNA clones from a
      phage display selected prostate tumour cDNA library with autologous patient
      antibodies and identified several relevant antigens such as NY-ESO-1, XAGE-1, DJ
      1 and transcription factor 25 (TCF25). The present high-throughput
      immunoscreening method has the potential to identify both patient-specific and
      disease-specific antigens for use in diagnostics and therapy.

PMID- 18045612
TI  - Nest volatiles as modulators of nestmate recognition in the ant Camponotus
      fellah.
AB  - When ants from alien colonies encounter each other the stereotypic reaction is
      usually one of aggressive behavior. It has been shown that factors such as queen
      derived cues or nest-odors modulate this reaction. Here we examined whether nest
      volatiles affect nestmate recognition by observing the reaction of nestmates
      towards individual workers under one of four regimes: completely isolated;
      isolated but receiving a constant airflow from the mother colony; as previous but
      with the passage of nest volatiles towards the isolated ants blocked by
      adsorption on a SuperQ column; or reversed airflow direction-from the isolated
      ants to the nest interior. Ants that had been completely isolated for three weeks
      were subjected to aggressive behavior, but not those that had continued to
      receive airflow from the mother colony. Adsorbing the nest volatiles from the
      airflow by SuperQ abolished this difference, with these ants now also being
      subjected to aggression, indicating that nest volatiles can modulate nestmate
      recognition. Reverse airflow also reduced the level of aggression but to a lesser
      extent than airflow directed from the mother colony. In queenless colonies the
      overall aggression was reduced under all regimes, and there was no effect of
      flow, suggesting that the volatiles involved are queen-borne. The SuperQ adsorbed
      volatiles originated from Dufour's gland secretions of both workers and queen,
      implicating them in the process. Cuticular hydrocarbon profiles were not affected
      by exposure to nest volatiles, suggesting that the latter either constitute part
      of the recognition cues or affect worker behavior via a different, as yet elusive
      mechanism.

PMID- 18045613
TI  - Kv4.3 is not required for the generation of functional Ito,f channels in adult
      mouse ventricles.
AB  - Accumulated evidence suggests that the heteromeric assembly of Kv4.2 and Kv4.3
      alpha-subunits underlies the fast transient Kv current (I(to,f)) in rodent
      ventricles. Recent studies, however, demonstrated that the targeted deletion of
      Kv4.2 results in the complete elimination of I(to,f) in adult mouse ventricles,
      revealing an essential role for the Kv4.2 alpha-subunit in the generation of
      mouse ventricular I(to,f) channels. The present study was undertaken to
      investigate directly the functional role of Kv4.3 by examining the effects of the
      targeted disruption of the KCND3 (Kv4.3) locus. Mice lacking Kv4.3 (Kv4.3-/-)
      appear indistinguishable from wild-type control animals, and no structural or
      functional abnormalities were evident in Kv4.3-/- hearts. Voltage-clamp
      recordings revealed that functional I(to,f) channels are expressed in Kv4.3-/-
      ventricular myocytes, and that mean I(to,f) densities are similar to those
      recorded from wild-type cells. In addition, I(to,f) properties (inactivation
      rates, voltage dependences of inactivation and rates of recovery from
      inactivation) in Kv4.3-/- and wild-type mouse ventricular myocytes were
      indistinguishable. Quantitative RT-PCR and Western blot analyses did not reveal
      any measurable changes in the expression of Kv4.2 or the Kv channel interacting
      protein (KChIP2) in Kv4.3-/- ventricles. Taken together, the results presented
      here suggest that, in contrast with Kv4.2, Kv4.3 is not required for the
      generation of functional mouse ventricular I(to,f) channels.

PMID- 18045615
TI  - Polymorphisms of Transferrin gene are associated with schizophrenia in Chinese
      Han population.
AB  - Several recent studies have provided evidence that abnormalities in
      oligodendrocyte and myelin function may contribute to the etiopathology of
      schizophrenia. Transferrin (TF), an iron transport glycoprotein playing an
      important role in synthesis of myelin and the development of oligodendrocytes,
      has been identified as down-regulated expression in schizophrenia brain by
      microarray, quantitative PCR and in situ hybridization method. In order to
      further assess the role of TF in schizophrenia, we examined seven polymorphisms
      in TF region using a set sample of Chinese Han subjects consisting of 326
      schizophrenia patients and 344 healthy controls. Four single nucleotide
      polymorphisms (SNPs) namely, rs4481157, rs3811655, rs6762415 and rs1405022 were
      analyzed in this study. Our results showed that one intronic SNP had strong
      association with schizophrenia (rs3811655: allele C>G, P=1.34E-6, OR=1.89, 95%
      CI=1.46-2.46; genotype P=3.72E-6). Two haplotypes A-C and G-G constructed of
      rs4481157-rs3811655 also revealed significant associations with schizophrenia
      (global P=0.0001). Our findings support that TF gene may be involved in
      susceptibility to schizophrenia in the Chinese Han population. However, further
      studies are needed to confirm these findings in other populations and to identify
      functional variants in TF that may be implicated in pathogenesis.

PMID- 18045616
TI  - Effects of short-term zidovudine exposure on mitochondrial DNA content and
      succinate dehydrogenase activity of rat skeletal muscle cells.
AB  - Long-term use of zidovudine (AZT) may cause mitochondrial abnormalities in
      various tissues, including a toxic myopathy in AIDS patients associated with
      mitochondrial DNA (mtDNA) depletion. In the present study, we examine the short
      term (48 h) effect of AZT (10, 30 and 100 microg/ml) on the mitochondrial
      succinate dehydrogenase (SDH) and mtDNA content of rat cultured skeletal muscle.
      The effect of AZT on cytochrome c oxidase (COX) enzyme was also analyzed. The
      histochemical quantitative analysis of SDH showed that AZT 10, 30 and 100
      microg/ml increased by 7%, 9% and 13% the mitochondrial content. Conversely,
      treatment of rat cultures with 10 to 100 microg/ml AZT reduced the mtDNA content
      by 23% to 66%, when compared to control values. The spontaneous contraction and
      the COX activity were not modified by up to 100 microg/ml AZT. Taken together,
      these results show that short-term treatment with AZT can induce severe
      myotoxicity that involves mitochondrial proliferation and mtDNA depletion in the
      rat cultured myotubes. Our results also indicate that rat cultured skeletal
      muscle might be a valuable in vitro assay to evaluate the effect of drugs on
      mitochondria to predict their potential to induce mitochondrial toxicity.

PMID- 18045614
TI  - Structural insight into the specific interaction between murine SHPS-1/SIRP alpha
      and its ligand CD47.
AB  - SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1
      or SIRP alpha/BIT) is an immunoglobulin (Ig) superfamily transmembrane receptor
      and a member of the signal regulatory protein (SIRP) family involved in cell-cell
      interaction. SHPS-1 binds to its ligand CD47 to relay an inhibitory signal for
      cellular responses, whereas SIRPbeta, an activating member of the same family,
      does not bind to CD47 despite sharing a highly homologous ligand-binding domain
      with SHPS-1. To address the molecular basis for specific CD47 recognition by SHPS
      1, we present the crystal structure of the ligand-binding domain of murine SHPS-1
      (mSHPS-1). Folding topology revealed that mSHPS-1 adopts an I2-set Ig fold, but
      its overall structure resembles IgV domains of antigen receptors, although it has
      an extended loop structure (C'E loop), which forms a dimer interface in the
      crystal. Site-directed mutagenesis studies of mSHPS-1 identified critical
      residues for CD47 binding including sites in the C'E loop and regions
      corresponding to complementarity-determining regions of antigen receptors. The
      structural and functional features of mSHPS-1 are consistent with the human SHPS
      1 structure except that human SHPS-1 has an additional beta-strand D. These
      results suggest that the variable complementarity-determining region-like loop
      structures in the binding surface of SHPS-1 are generally required for ligand
      recognition in a manner similar to that of antigen receptors, which may explain
      the diverse ligand-binding specificities of SIRP family receptors.

PMID- 18045617
TI  - Neutral networks of sequence to shape maps.
AB  - In this paper we present a combinatorial model of sequence to shape maps. Our
      particular construction arises in the context of representing nucleotide
      interactions beyond Watson-Crick base pairs and its key feature is to replace
      biophysical steric by combinatorial constraints. We show that these combinatory
      maps produce exponentially many shapes and induce sets of sequences which contain
      extended connected subgraphs of diameter n, where n denotes the length of the
      sequence. Our main result is to prove the existence of exponentially many shapes
      that have neutral networks.

PMID- 18045618
TI  - Kinetic properties required for sustained or paradoxical control of metabolic
      fluxes under large changes in enzyme activities.
AB  - The effect that an increase in the activity of an enzyme has on its flux normally
      decreases with activity increase. To achieve a large increase in flux by
      manipulating a single step would therefore require a high initial effect that
      maintains or increases when the activity is increased, what has been called
      sustained or paradoxical control. Using metabolic control analysis for large
      responses, we derive conditions for sustained or paradoxical control in terms of
      elasticity coefficients. These are used to characterise types of rate laws
      contributing to this behaviour. The result that simple pathways, with normal
      kinetics, subject to large activity changes can lead to paradoxical control
      behaviour suggests that this type of pattern may be much more ubiquitous than
      could have, in principle, been suspected.

PMID- 18045619
TI  - A model for the evolutionary maintenance of monogyny in spiders.
AB  - Sexual selection theory predicts that males should attempt to mate with several
      females, unless the benefits of male promiscuity are trumped by alternative
      benefits associated with male monogamy (monogyny). Here we use a game theory
      model to address the adaptive value of a monogynous strategy, which has the sole
      benefit of enhancing a male's paternity share in the context of competition with
      other males. We consider two ways in which monogynists might enhance their
      paternity: by outcompeting rival ejaculates in sperm competition, and by reducing
      the probability that a female remates with rival males. The model is based on the
      biology of some particularly well-studied spider species, in which males are
      morphologically restricted to mate with either one or at most two females in
      their lifetime. Our results suggest that, regardless of the mechanism of
      paternity enhancement involved, a male-biased sex ratio is generally required for
      the evolution and maintenance of monogyny. Moreover, we show that there is a
      large region of parameter space where monogyny and bigyny can coexist as
      alternative mating strategies under negative frequency dependent selection. There
      is also a narrow range of conditions where either monogyny or bigyny can be
      evolutionarily stable. Our results are in qualitative agreement with empirical
      findings in spiders.

PMID- 18045620
TI  - Central and local limit theorems for RNA structures.
AB  - A k-noncrossing RNA pseudoknot structure is a graph over {1,...,n} without 1
      arcs, i.e. arcs of the form (i,i+1) and in which there exists no k-set of
      mutually intersecting arcs. In particular, RNA secondary structures are 2
      noncrossing RNA structures. In this paper we prove a central and a local limit
      theorem for the distribution of the number of 3-noncrossing RNA structures over n
      nucleotides with exactly h bonds. Our analysis employs the generating function of
      k-noncrossing RNA pseudoknot structures and the asymptotics for the coefficients.
      The results of this paper explain the findings on the number of arcs of RNA
      secondary structures obtained by molecular folding algorithms and are of
      relevance for prediction algorithms of k-noncrossing RNA structures.

PMID- 18045621
TI  - Emergence and resilience of cooperation in the spatial prisoner's dilemma via a
      reward mechanism.
AB  - We study the problem of the emergence of cooperation in the spatial Prisoner's
      Dilemma. The pioneering work by Nowak and May [1992. Evolutionary games and
      spatial chaos. Nature 415, 424-426] showed that large initial populations of
      cooperators can survive and sustain cooperation in a square lattice with imitate
      the-best evolutionary dynamics. We revisit this problem in a cost-benefit
      formulation suitable for a number of biological applications. We show that if a
      fixed-amount reward is established for cooperators to share, a single cooperator
      can invade a population of defectors and form structures that are resilient to re
      invasion even if the reward mechanism is turned off. We discuss analytically the
      case of the invasion by a single cooperator and present agent-based simulations
      for small initial fractions of cooperators. Large cooperation levels, in the
      sustainability range, are found. In the conclusions we discuss possible
      applications of this model as well as its connections with other mechanisms
      proposed to promote the emergence of cooperation.

PMID- 18045622
TI  - Mechanisms of the vasorelaxant effect of 1, 5-dihydroxy-2, 3-dimethoxy-xanthone,
      an active metabolite of 1-hydroxy-2, 3, 5-trimethoxy-xanthone isolated from a
      Tibetan herb, Halenia elliptica, on rat coronary artery.
AB  - 1, 5-Dihydroxy-2, 3-dimethoxy-xanthone (HM-5) is one of the naturally-occurring
      xanthones of a Tibetan medicinal herb Halenia elliptica. Recently, it has been
      shown that HM-5 is one of the phase I metabolites of 1-hydroxy-2, 3, 5-trimethoxy
      xanthone (HM-1), the major active component of H. elliptica with potent
      vasorelaxant actions. This study investigated the vasorelaxant effect of HM-5 and
      its mechanism(s). HM-5 (0.35-21.9 microM) produced a concentration-dependent
      relaxation in rat coronary artery rings pre-contracted with 1 microM 5
      hydroxytryptamine (5-HT), with an EC(50) of 4.40+/-1.08 microM. Unlike HM-1, the
      effect of HM-5 was endothelial-independent such that removal of the endothelium
      did not affect its vasodilator potency. Nitric oxide synthase (NOS) inhibitor
      N(omega)-nitro-l-arginine methyl ester (l-NAME, 100 microM), the soluble
      guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one
      (ODQ, 10 microM) did not affect the vasodilatory effects of HM-5, thus confirming
      the non-involvement of endothelium related mechanisms. In endothelium-denuded
      coronary artery rings, the vasorelaxant effect of HM-5 was inhibited by a
      potassium channel blocker, TEA (10 mM), and 4-aminopyridine (4-AP, a K(v)
      blocker; 1 mM) but not by other K+ channel blockers such as iberiotoxin (100 nM),
      barium chloride (100 microM) and glibenclamide (10 microM). The involvement of
      Ca2+ channel was studied in artery rings pre-incubated with Ca2+-free buffer
      (intact endothelium or endothelium-denuded) and primed with 1 microM 5-HT or 60
      mM KCl prior to the addition of CaCl2 to elicit contraction. In the 5-HT-primed
      preparations, HM-5 (34.7 microM) significantly inhibited the CaCl(2)-induced
      vasoconstriction (89.9% inhibition in intact endothelium artery rings; 83.3%
      inhibition in endothelium-denuded rings). In the KCl-primed preparations, HM-5
      (34.7 microM) produced a 34% inhibition in endothelium-denuded rings. The same
      concentration of HM-5 inhibited (by 62.3%) the contractile response to 10 microM
      phorbol 12, 13-diacetate (PDA), a protein kinase C activator, in Ca2+-free
      solutions. Taken together, this study showed that the mechanisms of the
      vasorelaxant effects of HM-5 were distinctly different from those of its parent
      drug HM-1. The vasorelaxant effect of HM-5 was mediated through opening of
      potassium channel (4-AP) and altering intracellular calcium by partial inhibition
      of Ca2+ influx through L-type voltage-operated Ca2+ channels and intracellular
      Ca2+ stores.

PMID- 18045623
TI  - Cav1.2 calcium channels modulate the spiking pattern of hippocampal pyramidal
      cells.
AB  - Ca(v)1.2 L-type calcium channels support hippocampal synaptic plasticity, likely
      by facilitating dendritic Ca2+ influx evoked by action potentials (AP) back
      propagated from the soma. Ca2+ influx into hippocampal neurons during somatic APs
      is sufficient to activate signalling pathways associated with late phase LTP.
      Thus, mechanisms controlling AP firing of hippocampal neurons are of major
      functional relevance. We examined the excitability of CA1 pyramidal cells using
      somatic current-clamp recordings in brain slices from control type mice and mice
      with the Ca(v)1.2 gene inactivated in principal hippocampal neurons. Lack of the
      Ca(v)1.2 protein did not affect either affect basic characteristics, such as
      resting membrane potential and input resistance, or parameters of single action
      potentials (AP) induced by 5 ms depolarising current pulses. However, CA1
      hippocampal neurons from control and mutant mice differed in their patterns of AP
      firing during 500 ms depolarising current pulses: threshold voltage for
      repetitive firing was shifted significantly by about 5 mV to more depolarised
      potentials in the mutant mice (p<0.01), and the latency until firing of the first
      AP was prolonged (73.2+/-6.6 ms versus 48.1+/- 7.8 ms in control; p<0.05). CA1
      pyramidal cells from the mutant mice also showed a lowered initial spiking
      frequency within an AP train. In control cells, isradipine had matching effects,
      while BayK 8644 facilitated spiking. Our data demonstrate that Ca(v)1.2 channels
      are involved in regulating the intrinsic excitability of CA1 pyramidal neurons.
      This cellular mechanism may contribute to the known function of Ca(v)1.2 channels
      in supporting synaptic plasticity and memory.

PMID- 18045624
TI  - Effects of heavy metal contamination on the macrobenthic fauna in estuaries: the
      case of the Seine estuary.
AB  - Heavy metal contamination levels are generally higher in estuaries than in the
      open sea. Some estuaries, the Seine estuary for example, have particularly high
      pollution levels of metals, yet continue to support a very high benthic biomass
      and remain quite productive. Measurements of sediment contamination are highly
      variable due to diverse chemical analysis methods, sediments origin and sources
      of contaminants found in the estuaries. Salinity appears to be the principal
      factor controlling contaminant distribution in the sediment and the overlying
      and/or interstitial waters; it also affects the bioavailability of contaminants
      in estuarine sediments. Of course, the response to contaminants varies greatly
      among species and assemblages. Trace metals explain only a small part of the
      variation in benthic community structure. Some species, such as the shrimp
      Crangon crangon, appears vulnerable to metal pollution, while other species, such
      as Scrobicularia plana, are able to tolerate quite high levels of cadmium in
      their tissue. This paper demonstrates the wide variability of benthic responses
      to contamination, which is probably due to the high spatio-temporal heterogeneity
      of the estuary. To reduce the problems due the heterogeneity and variability
      observed to date in the available results, it will be necessary to encourage
      integrated estuarine studies, in which sedimentologists, chemists, and biologists
      work together on the same campaigns at the same sites.

PMID- 18045625
TI  - The performance of benthic indicators of ecological change in Adriatic coastal
      lagoons: throwing the baby with the water?
AB  - The ecological quality of 127 stations from six Adriatic coastal lagoons was
      assessed using a suite of biotic indices: H', d, 1-lambda', Delta(*), Delta(+),
      W, AMBI, BOPA and FINE. The analysis indicated the difficulties in deriving and
      using the existing indices from benthic communities in highly variable
      environmental conditions in coastal lagoons. Different metrics rendered different
      results: the use of H' resulted in the classification of all stations as
      "Moderate/Poor/Bad", whereas BOPA classified the majority of the stations as
      "Good/High". Using Delta(+), most of the stations resulted as "Not
      anthropogenically impacted", while the W-statistics gave 82 stations as
      "Undisturbed" and 45 as "Moderately/Grossly disturbed". AMBI classified 55
      stations as "High/Good" and 72 as "Moderate/Poor/Bad", whereas those were 32 and
      95 with FINE, respectively. The latter, which was developed just for Italian
      coastal lagoons, was the most conservative among the indices studied. Yet, it
      showed the highest correlation with the species/abundance matrix. Using indices
      developed for coastal waters in lagoons can give the distorted indication that
      the water body is degraded, when it might be just a natural, low diversity, high
      abundance community, i.e. a lagoonal community. Moreover, the outcome of the use
      of a certain index has a financial dimension such that lagoons misclassified as
      being "poor status" will then require expensive remediation measures. For the
      lagoons studied, there is probably an adequate quality and quantity of benthic
      data available for making management decisions, but this study highlights the
      limits of the existing indices for lagoonal ecosystems. The challenge for the
      next future is to couple long term conservation of the natural environment with
      the highly productive activities carried out in lagoonal ecosystems.

PMID- 18045626
TI  - Decreased anticonvulsant efficacy of allopregnanolone during ethanol withdrawal
      in female Withdrawal Seizure-Prone vs. Withdrawal Seizure-Resistant mice.
AB  - The GABAergic neurosteroid allopregnanolone (ALLO) has been repeatedly shown to
      have an increased anticonvulsant effect during ethanol withdrawal in rats and in
      C57BL/6J mice. In contrast, the seizure prone DBA/2J inbred strain and the
      Withdrawal Seizure-Prone (WSP) selected line exhibited decreased sensitivity to
      ALLO's anticonvulsant effect during ethanol withdrawal, with no change in
      sensitivity in the Withdrawal Seizure-Resistant (WSR) line. To date, only male
      mice have been tested. Thus, the present study examined ALLO sensitivity during
      ethanol withdrawal in female WSP and WSR mice, since females display less severe
      physical symptoms of withdrawal and have higher circulating ALLO levels than
      males. Female WSP and WSR mice were exposed to ethanol vapor or air for 72h.
      During peak ethanol withdrawal, separate groups of mice were injected with
      vehicle or ALLO (0, 3.2, 10, or 17mg/kg, i.p.) prior to the timed tail vein
      infusion of pentylenetetrazol (PTZ). ALLO injection significantly increased the
      threshold dose for onset to PTZ-induced convulsions, indicating an anticonvulsant
      effect, in female WSP and WSR mice. During ethanol withdrawal, sensitivity to
      ALLO's anticonvulsant effect was slightly increased in female WSR mice but was
      significantly decreased in female WSP mice. This line difference in sensitivity
      to ALLO during ethanol withdrawal in female mice was similar to that in the male
      mice. Notably, all seizure prone genotypes tested to date displayed tolerance to
      the anticonvulsant effect of ALLO during ethanol withdrawal, suggesting that
      decreased sensitivity of GABA(A) receptors to ALLO may contribute to the
      increased ethanol withdrawal phenotype.

PMID- 18045628
TI  - Changes in Heart Rate Variability during a tonic immobility test in quail.
AB  - Tonic immobility (TI) is an unlearned fear response induced by a brief physical
      restraint and characterized by a marked autonomic nervous system involvement.
      This experiment aimed at studying the relative involvement of both autonomic sub
      systems, the sympathetic and parasympathetic nervous systems, during TI, by
      analyzing Heart Rate Variability. Quail selected genetically for long (LTI) or
      short (STI) TI duration and quail from a control line (CTI) were used. The
      animals were surgically fitted with a telemetric device to record
      electrocardiograms before and during a TI test. Heart rate did not differ between
      lines at rest. The induction of TI, whether effective or not, induced an increase
      in HR characterized by a shift of the sympathovagal balance towards a higher
      sympathetic dominance. Parasympathetic activity was lower during effective than
      during non-effective inductions in CTI quail. During TI, the increase in
      sympathetic dominance was initially maintained and then declined, while relative
      parasympathetic activity remained low, especially in CTI and STI lines. The end
      of tonic immobility was characterized by a rise in overall autonomic activity in
      all lines and an increase in parasympathetic influence in CTI and STI quail. To
      conclude, the susceptibility to TI cannot be explained only by autonomic reflex
      changes. It is probably strongly related to the perception of the test by the
      quail. During TI, the differences between lines in autonomic responses probably
      reflect behavioural differences in the fear response.

PMID- 18045627
TI  - Withdrawal from chronic administration of cocaine decreases delta opioid receptor
      signaling and increases anxiety- and depression-like behaviors in the rat.
AB  - Chronic administration of cocaine has been shown to attenuate the functional
      capacity of delta opioid receptors to inhibit adenylyl cyclase activity. Abuse
      and withdrawal from cocaine in humans is associated with increases in anxiety and
      depression. Since recent research supports the role of delta opioid receptors in
      anxiety- and depression-like behaviors in rodents, we hypothesized that
      functional desensitization of delta opioid receptors contributes to anxiety- and
      depression-like behavioral phenotypes following short-term withdrawal from
      chronic administration of cocaine. To test this hypothesis, delta opioid receptor
      signaling and behaviors were evaluated 24h after 14days of binge-pattern cocaine
      administration (15mg/kg three times daily at 1h intervals) in male Sprague-Dawley
      rats. Results showed that the inhibition of adenylyl cyclase by delta opioid
      receptor agonists was attenuated in the frontal cortex, nucleus accumbens and
      caudate putamen 24h after cessation of cocaine administration. One day withdrawal
      from chronic administration of cocaine resulted in increased anxiety- and
      depression-like behaviors as measured by the elevated plus maze and the forced
      swim test respectively, and no change in locomotor activity. The anxiety- and
      depression-like behaviors were dose-dependently reduced by acute administration
      of the selective delta opioid receptor agonist, SNC80. These results demonstrate
      that early withdrawal from cocaine resulted in increased anxiety and depression,
      which accompanies the desensitization of delta opioid receptor function.
      Furthermore, cocaine-induced anxiety- and depression-like behaviors were
      reversible by the delta opioid receptor agonist SNC80.

PMID- 18045629
TI  - Effects of a bile acid elicitor, cholic acid, on the biosynthesis of diterpenoid
      phytoalexins in suspension-cultured rice cells.
AB  - An elicitor of rice defense responses was recently isolated from human feces and
      was identified as cholic acid (CA). Pathogen infection in rice leaves induces
      phytocassanes and momilactones, both of which are major diterpenoid phytoalexins
      in rice, whereas CA mainly induces phytocassanes. We established a high
      performance liquid chromatography-electrospray ionization-tandem mass
      spectrometry protocol for the rapid and accurate quantification of phytocassanes
      and momilactones. Using this method, we showed that CA preferentially induced the
      formation of phytocassanes in suspension-cultured rice cells, while a fungal
      chitin oligosaccharide elicitor induced that of both phytocassanes and
      momilactones. We further investigated the effects of CA on the expression of
      diterpene cyclase genes involved in phytoalexin biosynthesis. CA induced the
      transcription of the genes OsCPS2 (OsCyc2) and OsKSL7 (OsDTC1), which are
      involved in phytocassane biosynthesis, to a greater extent than the genes OsCPS4
      (OsCyc1) and OsKSL4, which are involved in momilactone biosynthesis. OsCPS2 was
      particularly strongly induced, suggesting that it is one of the main mechanisms
      by which CA induces high levels of phytocassanes.

PMID- 18045630
TI  - Trinorcucurbitane and cucurbitane triterpenoids from the roots of Momordica
      charantia.
AB  - Five cucurbitacins, kuguacins A-E (1-5), together with three known analogues,
      3beta,7beta,25-trihydroxycucurbita-5,(23E)-diene-19-al (6), 3beta,25-dihydroxy
      5beta,19-epoxycucurbita-6,(23E)-diene (7), and momordicine I (8), were isolated
      from roots of Momordica charantia. Structures of 1-5 were elucidated by NMR and
      MS spectroscopic analysis. Among them, compounds 3-5 possess an unprecedented
      25,26,27-trinorcucurbitane backbone. Compounds 3 and 5 showed moderate anti-HIV-1
      activity with EC(50) values of 8.45 and 25.62 microg/ml, and exerted minimal
      cytotoxicity against C8166 cells (IC(50)>200 microg/ml), with a selectivity index
      more than 23.68 and 7.81, respectively.

PMID- 18045631
TI  - The amniotic plaques in sheep of the Karagouniko breed.
AB  - The structure of amniotic plaques and adjacent epithelium of full term ewes of
      the Karagouniko breed were studied using scanning electron microscopy (SEM) and
      light microcopy. The amniotic plaques appeared as cauliflower-like structures
      mainly trifurcate or as single papillae. The wall of their stems possessed
      numerous foldings and round openings. Of interest to note was the abundant
      vascularization observed in sections of the amniotic plaques. The adjacent
      amniotic epithelium to the plaques revealed a heterogenous surface which was
      composed of cells of various forms.

PMID- 18045633
TI  - Suppression of aromatase in human breast cells by a cyclooxygenase-2 inhibitor
      and its analog involves multiple mechanisms independent of cyclooxygenase-2
      inhibition.
AB  - Previous studies have demonstrated that cyclooxygenase-2 (COX-2) inhibitor NS-398
      decrease aromatase activity at the transcript level in breast cancer cells.
      However, N-Methyl NS-398, which does not have COX-2 inhibitory activity but has
      very similar structure to NS-398, decreases aromatase activity and transcription
      in MCF-7 and MDA-MB-231 breast cells to the same extent as NS-398. This suggests
      that NS-398 decrease aromatase expression in breast cancer cells via other
      mechanism(s). Further investigations find that both compounds only decrease
      aromatase activity stimulated by forskolin/phorbol ester at the transcript level
      in both breast cancer cell lines and in breast stromal cells from patients. They
      do not affect aromatase expression and activity stimulated by dexamethasone. Both
      compounds also suppress MCF-7 cell proliferation stimulated by testosterone.
      Aromatase inhibition studies using placental microsomes demonstrate that the
      compounds show only weak direct aromatase inhibition. These results suggest that
      NS-398 and its N-methyl analog suppress aromatase expression and activity with
      multiple mechanisms.

PMID- 18045634
TI  - Specific cerebral heat shock proteins and histamine receptor cross-talking
      mechanisms promote distinct lead-dependent neurotoxic responses in teleosts.
AB  - Recent interests are beginning to be directed towards toxic neurobiological
      dysfunctions caused by lead (Pb) in aquatic vertebrates. In the present work,
      treatment with a maximum acceptable toxic concentration of this heavy metal was
      responsible for highly significant (p<0.01) abnormal motor behaviors such as
      hyperactive movements in the teleost Thalassoma pavo and the same treatment
      accounted for significantly (p<0.05) enhanced hyperventilating states. On the
      other hand, greater abnormal motor behaviors were detected in the presence of the
      histamine (HA) receptor subtype 2 (H(2)R) antagonist cimetidine (Cim), as shown
      by the very robust (p<0.001) increases of the two behavioral states.
      Interestingly, elevated expression levels of stress-related factors, i.e. heat
      shock protein70/90 (HSP90/70) orthologs were reported for the first time in
      hypothalamic and mesencephalic areas of Pb-treated teleosts. In particular, an up
      regulation of HSP70 was readily detected when this heavy metal was given
      concomitantly with Cim, while the histamine subtype 3 antagonist (H(3)R)
      thioperamide (Thio), instead, blocked Pb-dependent up-regulatory trends of both
      chaperones in mostly hypothalamic areas. Moreover, intense neuronal damages of
      the above brain regions coincided with altered expressions of HSP70 and HSP90
      when treated only with Cim. Overall these first results show that distinct H(n)R
      are able to exert a net neuroprotective role arising from their interaction with
      chaperones in fish exposed to Pb-dependent stressful conditions making this a
      potentially key interaction especially for T. pavo, aquatic species which plays
      an important ecological role towards the survival of other commercially vital
      fishes.

PMID- 18045635
TI  - On the presence of antibodies against bovine, equine and poultry immunoglobulins
      in human IgG preparations, and its implications on antivenom production.
AB  - Specific immunoassays were developed to detect anti-horse, anti-chicken and anti
      bovine immunoglobulins in human IgG preparations. Three samples of 5% human IgG
      for intravenous use ("Inmunoglobulina G Endovenosa al 5%"(trade mark), Quimbiotec
      CA), were studied. All samples were produced from pools of >2500 plasma units
      from different donors. One sample was produced from an only Venezuelan plasma
      pool (2660 donors) and the other two were produced from a 1:1 blend of Venezuelan
      and Canadian plasma pools. The amounts of human IgG detected were 0.017
      (0.015,0.020) mg/ml (n=18) against horse IgG, 0.37 (0.28, 0.48) mg/ml (n=18)
      against cattle IgG and 1.27 (1.15, 1.40) mg/ml (n=15) against chicken IgY.
      Similar results were obtained on individual Venezuelan plasma samples. The
      differences probably reflect the consumption and antigenicity of meat. Poultry
      and bovine meat are widely consumed in Venezuela and Canada, while equine meat is
      not consumed; also chicken is more heterologous to man and may be more antigenic
      than bovine meat. This suggests that when IgY immunotherapeutics are used in
      populations with an important dietary component of poultry meat and eggs, there
      is a risk of producing untoward reactions and less efficient antivenoms.

PMID- 18045636
TI  - Vascular permeability and vasodilation induced by the Loxosceles intermedia venom
      in rats: involvement of mast cell degranulation, histamine and 5-HT receptors.
AB  - The mechanisms involved in both local and systemic effects of Loxosceles
      intermedia (brown spider) venom (LIV) are still poorly understood. We show using
      rats treated with Evans blue dye (50 mg/kg, i.v.) that small doses of the LIV
      (0.1, 0.3, 1 and 3 microg/site) dose-dependently increase the vascular
      permeability in rats, an effect unchanged by indomethacin (5mg/kg, i.p.),
      atropine (1mg/kg, i.p.), HOE-140 (2mg/kg, s.c.) or SR140333 (0.3mg/kg, i.p.), but
      fully avoided by promethazine (15 mg/kg, i.p.), methysergide (2mg/kg, i.p.) and
      compound 48/80 (3mg/kg/day for 3 days). Addition of cumulative concentrations of
      LIV (0.1-5 microg) in phenylephrine-contracted aortic rings resulted in a partial
      ( approximately 40%) and endothelium-dependent relaxation, inhibited by the
      nitric oxide synthase inhibitors L-NAME (10 microM) and L-NMMA (1mM), and the
      guanylate cyclase inhibitors methylene blue (100 microM) and ODQ (10 microM). LIV
      induced relaxation was abolished by compound 48/80 (10 microM) and pyrilamine (a
      selective histamine H1 receptor antagonist; 100 microM), but not by atropine (1
      microM) and indomethacin (10 microM). Our results disclose that LIV increases
      vascular permeability and induces vascular relaxation. These effects occur due to
      its ability to degranulate mast cells and release mediators such as histamine and
      serotonin.

PMID- 18045637
TI  - Micro-stereolithography as a transducer design method.
AB  - This paper investigates the use of micro-stereolithography, a rapid prototyping
      technique, in the manufacture of transducers. It is illustrated for the
      production of electromagnetic acoustic transducer (EMATs) coils in both meander
      line and spiral configurations. A synthetic aperture focussing technique (SAFT)
      has been applied to the ultrasonic signals from these devices to reconstruct
      images in metallic objects.

PMID- 18045638
TI  - The number of herpes simplex virus-infected neurons and the number of viral
      genome copies per neuron correlate with the latent viral load in ganglia.
AB  - The latent viral load is the most important factor that predicts reactivation
      rates of animals latently infected with herpes simplex virus (HSV). To estimate
      the latent viral load, individual latently infected mouse trigeminal ganglia were
      dispersed into single cell suspensions and plated into 96-well real-time PCR
      plates, and HSV-2 genome copies were measured. By assuming a Poisson distribution
      for both the number of HSV-2 infected cells per well and the number of HSV-2
      genome copies per infected cell, the numbers of infected cells and mean genome
      copies per infected cell were determined. Both the number of HSV-2 infected cells
      and the mean HSV-2 genome copy per infected cell significantly correlated with
      the latent viral load (p<10(-4)), indicating that both factors are responsible
      for the increase in the latent viral load.

PMID- 18045639
TI  - Molecular characterization of L-413C, a P2-related plague diagnostic
      bacteriophage.
AB  - Our analysis of the plague diagnostic phage L-413C genome sequence and structure
      reveals that L-413C is highly similar and collinear with enterobacteriophage P2,
      though important differences were found. Of special interest was the mosaic
      nature of the tail fiber protein H in L-413C, given the differentiating
      specificity of this phage for Yersinia pestis vs. Yersinia pseudotuberculosis.
      While the N-terminal 207 and C-terminal 137 amino acids of L-413C display
      significant homology with the P2 H protein, a large (465 amino acid) middle
      section appears to be derived from a T4-related H protein, with highest
      similarity to the T6 and RB32 distal tail fibers. This finding along with
      appropriate preadsorption experiments suggest that the unique H protein of L-413C
      may be responsible for the specificity of this phage for Y. pestis, and that the
      Y. pestis receptors that are recognized and bound by L-413C either do not exist
      in Y. pseudotuberculosis or have a different structure.

PMID- 18045640
TI  - Autographa californica multiple nucleopolyhedrovirus ac142, a core gene that is
      essential for BV production and ODV envelopment.
AB  - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac142 is a
      baculovirus core gene and encodes a protein previously shown to associate with
      occlusion-derived virus (ODV). To determine its role in the baculovirus life
      cycle, we used the AcMNPV bacmid system to generate an ac142 deletion virus
      (AcBAC(ac142KO-PH-GFP)). Fluorescence and light microscopy revealed that
      AcBAC(ac142KO-PH-GFP) exhibits a single-cell infection phenotype. Titration
      assays and Western blot confirmed that AcBAC(ac142KO-PH-GFP) is unable to produce
      budded virus (BV). However, viral DNA replication is unaffected and the
      development of occlusion bodies in AcBAC(ac142KO-PH-GFP)-transfected cells
      evidenced progression to very late phases of the viral infection. Western blot
      analysis showed that AC142 is expressed in the cytoplasm and nucleus throughout
      infection and that it is a structural component of BV and ODV which localizes to
      nucleocapsids. Electron microscopy indicates that ac142 is required for
      nucleocapsid envelopment to form ODV and their subsequent occlusion, a
      fundamental process to all baculoviruses.

PMID- 18045641
TI  - Chlorella viruses evoke a rapid release of K+ from host cells during the early
      phase of infection.
AB  - Infection of Chlorella NC64A cells by PBCV-1 produces a rapid depolarization of
      the host probably by incorporation of a viral-encoded K(+) channel (Kcv) into the
      host membrane. To examine the effect of an elevated conductance, we monitored the
      virus-stimulated efflux of K(+) from the chlorella cells. The results indicate
      that all 8 chlorella viruses tested evoked a host specific K(+) efflux with a
      concomitant decrease in the intracellular K(+). This K(+) efflux is partially
      reduced by blockers of the Kcv channel. Qualitatively these results support the
      hypothesis that depolarization and K(+) efflux are at least partially mediated by
      Kcv. The virus-triggered K(+) efflux occurs in the same time frame as host cell
      wall degradation and ejection of viral DNA. Therefore, it is reasonable to
      postulate that loss of K(+) and associated water fluxes from the host lower the
      pressure barrier to aid ejection of DNA from the virus particles into the host.

PMID- 18045642
TI  - Polychlorinated biphenyls (PCBs) and hydroxy-PCBs in adipose tissue of women in
      Southeast Spain.
AB  - Polychlorinated biphenyls (PCBs) and hydroxylated PCBs (OH-PCBs) were
      investigated in human adipose tissue samples collected from 20 women undergoing
      surgery. Mean sum of PCB and sum of OH-PCB levels were 737ng/g of lipid and 8pg/g
      of lipid, respectively. Among PCBs, congeners 180, 153, 138 and 170 were the most
      frequent and abundant, and together constituted 72% of the total amount of PCBs
      in adipose tissue. The PCB congener pattern and the frequencies and
      concentrations of non-dioxin-like and non-hydroxylated congeners observed in
      adipose tissue were similar in distribution and order of magnitude to the profile
      previously published in Spain but lower than that found in other European
      countries. Among OH-PCB congeners studied, 4-OH-PCB 107/118 was found at the
      highest concentrations followed by 3'-OH-PCB 180 and 3-OH-PCB 138. To date, no
      information on levels of PCB metabolites in the Spanish population is available
      for comparison. These three predominant OH-PCBs contributed 97% of all OH-PCBs.
      Twelve dioxin-like PCBs contributed around 8% of the total PCB exposure, and all
      were present in all study subjects. Further research is required to determine
      trends in human exposure to PCBs and OH-PCBs and how existing banning measures
      affect exposure.

PMID- 18045643
TI  - Effect of a full-grown vegetative filter strip on herbicide runoff: maintaining
      of filter capacity over time.
AB  - Narrow vegetative filter strips (VFS) proved to effectively reduce herbicide
      runoff from cultivated fields mainly due to the ability of vegetation to delay
      surface runoff, promote infiltration and adsorb herbicides. Since VFS are dynamic
      systems, their performance would not remain constant over the years indicating
      the need to define suitable buffer management. In order to evaluate the
      performance of different five and six year-old VFS, the runoff of the herbicides
      metolachlor and terbuthylazine was monitored in 2002 and 2003 in an experimental
      site in northern Italy. The structure of the herbaceous cover in the buffers
      changes over time. When rows of trees are present, the grass cover is decreased
      by the shading action of the trees, but the leaf litter gains importance. In VFS
      with grass cover only, the cover composition changes because of the substitution
      of grass by broadleaf species. Six metres wide VFS are very effective in reducing
      runoff volume and concentration during both wet and dry years. Classification
      analysis showed that runoff concentration and volume are linked to the
      characteristics of the rainfall event, buffer, source of herbicides and time
      after application. Regression analysis showed that the significant predictors for
      runoff volume are rainfall amount and intensity, total vegetal cover in the VFS,
      crop leaf area index and time after treatment; for concentration they are
      rainfall intensity, crop leaf area index and total vegetal cover in the VFS. The
      role of VFS is complex, so appropriate management is required to maintain its
      increasing filtering capacity over time.

PMID- 18045644
TI  - Expression of cystic fibrosis transmembrane conductance regulator in the human
      distal lung.
AB  - The determination of the expression of cystic fibrosis transmembrane conductance
      regulator (CFTR) in the lung is essential for a full understanding of the normal
      lung physiology and the pathogenesis of the lung disease in cystic fibrosis (CF).
      However, studies on the expression of CFTR in the distal adult human lung have
      yielded conflicting results despite functional evidence of expression of CFTR in
      bronchiolar and alveolar epithelial cells. We used 2 high-affinity monoclonal
      anti-CFTR antibodies, MAb24-1 and MAb13-1, to determine the expression of CFTR in
      samples of bronchiolar and alveolar tissues obtained from the same non-CF
      individuals. CFTR immunostaining was detected in the epithelium of bronchiolar
      and alveolar tissues. The staining pattern was similar with both antibodies. In
      bronchioles, CFTR labeling was present mostly in ciliated cells; in alveoli, CFTR
      labeling was detected in both type I and type II cells. We conclude that CFTR is
      expressed in human bronchiolar and alveolar epithelial cells. The potential
      importance of CFTR expression in alveoli should be further investigated,
      particularly with respect to the CF lung disease and the physiology of the
      alveolar region.

PMID- 18045645
TI  - Expression and prognostic role of MMP2, MMP9, MMP13, and MMP14 matrix
      metalloproteinases in sinonasal and oral malignant melanomas.
AB  - Sinonasal and oral malignant melanomas are rare malignancies accounting for less
      than 2% of all melanomas. Matrix metalloproteinases (MMPs) are proteolytic
      enzymes required for extracellular matrix degradation in a variety of
      physiological and pathologic processes including wound healing, embryogenesis,
      tumor invasion, and metastases. We studied the correlation between expression of
      MMPs, nucleolar diameter of melanoma cells, different clinical and histologic
      parameters, and patient's outcome. Seventeen cases of sinonasal and oral
      malignant melanoma were studied. The expression of MMP2, MMP9, MMP13, and MMP14
      was assessed immunohistochemically on paraffinized sections and measured by
      computer morphometry as well as silver-stained nucleolar diameter. A significant
      correlation was found between MMP2 and MMP14 expression and patient's outcome.
      Greater overall survival was seen in patients with average MMP2 expression less
      than 8000 microm(2)/x20 high-power field (P = .016). In patients with negative
      MMP14 staining, survival rate by the end of the follow-up was 38% compared with
      patients with positive MMP14 staining where survival rate was 0 (P = .03). A
      correlation with age at onset was also found; patients younger than 66 years had
      better overall survival rates than patients aged 66 years or older (P = .03). The
      maximal nucleolar diameter (MaxND) was another parameter that significantly
      correlated with clinical outcome. Patients with MaxND of 8 microm or larger
      showed a significant worse prognosis compared with the group with MaxND less than
      8 microm (P = .0009). Our pilot study demonstrates that MMP2, MMP14, MMP9, and
      MaxND might be used as prognostic markers in patients with sinonasal and oral
      malignant melanoma.

PMID- 18045646
TI  - Epidermal growth factor receptor: a novel biomarker for aggressive head and neck
      cutaneous squamous cell carcinoma.
AB  - There is currently no prognostic tool that reliably predicts the risk of
      metastasis in cutaneous squamous cell carcinoma, most of which occur in the head
      and neck region. Epidermal growth factor receptor has received much interest in
      recent years with the advent of epidermal growth factor receptor-targeted
      molecular therapy in clinical oncology. We investigate the role of epidermal
      growth factor receptor as a biomarker for head and neck cutaneous squamous cell
      carcinoma. Using immunohistochemistry and fluorescence in situ hybridization, we
      assessed the epidermal growth factor receptor protein expression and gene copy in
      3 groups of head and neck cutaneous squamous cell carcinoma: primary lesions not
      associated with metastasis (P), primary lesions associated with subsequent
      metastasis (PM), and metastatic nodal disease (M). Epidermal growth factor
      receptor overexpression was detected in 36% and 79% of P and PM cases,
      respectively. Epidermal growth factor receptor overexpression was significantly
      associated with PM (P = .03) and was found to be an independent prognostic factor
      for metastasis on multivariate analysis (P = .05). However, epidermal growth
      factor receptor overexpression was only maintained in 47% of cases in the M
      group. None of the 27 cases that overexpressed the epidermal growth factor
      receptor protein showed gene amplification: the results were uninterpretable in
      2, and polysomy and balanced disomy were detected in 5 and 20 cases,
      respectively. These observations may have important prognostic and therapeutic
      implications for head and neck cutaneous squamous cell carcinoma.

PMID- 18045647
TI  - Basal-HER2 phenotype shows poorer survival than basal-like phenotype in hormone
      receptor-negative invasive breast cancers.
AB  - Previous studies have shown conflicting results on prognostic significance of
      basal-like breast tumors, but hormone receptor is a confusing factor in most of
      the prognostic evaluations. We aimed to characterize the prognostic features of
      basal-like tumors without the influence of hormone receptor status in a series of
      hormone receptor-negative breast tumors. Using tissue microarray and
      immunohistochemistry methods, according to the expression of HER2 and basal
      markers (CK5/6, CK14, EGFR), we categorized 713 consecutive hormone receptor
      negative invasive breast cancers into 3 subtypes: HER2 (HER2+), basal-like (HER2
      , any basal marker+), and null (HER2-, all basal markers-). The HER2 phenotype
      was subdivided into pure-HER2 (HER2+, all basal markers-) and basal-HER2 (HER2+,
      any basal marker+) subgroups. Expression of p53, p63, vimentin, and BRCA1 was
      assessed immunochemically. Basal-like tumors showed significantly higher grade,
      more frequent recurrence, and higher expression of vimentin and p63 than HER2 and
      null phenotypes. Basal-HER2 phenotype had significantly younger mean age and
      expressed a higher level of p53 and vimentin like basal-like and/or HER2
      phenotypes. However, unlike all the other hormone receptor-negative phenotypes,
      they highly expressed BRCA1. No significant difference was found in 5-year
      survival among basal-like and the other hormone receptor-negative phenotypes,
      except for basal-HER2, which showed poorer 5-year overall survival than basal
      like tumors. In conclusion, although basal-like breast tumors have distinct
      clinicopathologic and immunohistochemical features, they have similar 5-year
      survival compared with the other hormone receptor-negative tumors including HER2
      and null phenotypes. However, there exists a small group of hormone receptor
      negative tumors expressing HER2 and basal markers simultaneously. This small
      group of tumors showed significantly poorer 5-year overall survival than basal
      like breast tumors and might require different treatment strategy.

PMID- 18045648
TI  - Trials of new germ cell immunohistochemical stains in 93 extragonadal and
      metastatic germ cell tumors.
AB  - Organic cation transporter 3/4 (OCT3/4) is a transcription factor of embryonic
      stem cells; c-kit (CD117) is a tyrosine kinase receptor implicated in seminoma
      carcinogenesis. Their reactivity is well characterized in testicular, but not
      extragonadal and metastatic, germ cell tumors. A total of 93 germ cell tumors (41
      seminoma, 22 embryonal carcinoma, 18 teratoma, and 12 yolk sac tumor) were
      obtained from the central nervous system (30), mediastinum (23),
      retroperitoneum/abdomen (31), and other locations (9). Immunohistochemical
      staining for c-kit, placental-like alkaline phosphatase (PLAP), OCT3/4, and new
      markers D2-40 and AP-2gamma was performed on seminomas; CD30 and epithelial
      membrane antigen were added for nonseminomas. In embryonal carcinoma, c-kit
      reacted in 17 of 22 cases, OCT3/4 in 18 of 22, and PLAP in 13 of 22. OCT3/4 was
      superior to PLAP in intensity and percent cells staining. In seminoma, OCT3/4 and
      D2-40 were superior to PLAP in intensity and percent cells; c-kit and AP-2gamma
      were superior in percent cells. D2-40 stained 23 of 24 seminomas strongly but had
      only weak focal reactivity in 6 of 17 embryonal carcinomas. Sensitivity and
      specificity were high for OCT3/4 discriminating seminoma and embryonal carcinoma,
      and c-kit discriminating seminoma, from other germ cell tumors. For embryonal
      carcinoma, OCT3/4 had higher specificity (0.94) than CD30 (0.786) owing to CD30
      reactivity in 3 of 10 teratomas. Epithelial membrane antigen discriminated
      teratoma from other nonseminomas with a sensitivity of 1 but reacted occasionally
      in embryonal carcinoma (3/15) and yolk sac tumor (2/7). In conclusion, for
      extragonadal seminoma, OCT3/4, AP-2gamma, D2-40, and c-kit were equivalently
      superior to PLAP. For embryonal carcinoma, OCT3/4 was superior to PLAP and more
      specific than CD30. D2-40 is recommended to discriminate between seminoma and
      embryonal carcinoma.

PMID- 18045649
TI  - Incremental dental development: methods and applications in hominoid evolutionary
      studies.
AB  - This survey of dental microstructure studies reviews recent methods used to
      quantify developmental variables (daily secretion rate, periodicity of long
      period lines, extension rate, formation time) and applications to the study of
      hominoid evolution. While requisite preparative and analytical methods are time
      consuming, benefits include more precise identification of tooth crown initiation
      and completion than conventional radiographic approaches. Furthermore,
      incremental features facilitate highly accurate estimates of the speed and
      duration of crown and root formation, stress experienced during development
      (including birth), and age at death. These approaches have provided insight into
      fossil hominin and Miocene hominoid life histories, and have also been applied to
      ontogenetic and taxonomic studies of fossil apes and humans. It is shown here
      that, due to the rapidly evolving nature of dental microstructure studies,
      numerous methods have been applied over the past few decades to characterize the
      rate and duration of dental development. Yet, it is often unclear whether data
      derived from different methods are comparable or which methods are the most
      accurate. Areas for future research are identified, including the need for
      validation and standardization of certain methods, and new methods for
      integrating nondestructive structural and developmental studies are highlighted.

PMID- 18045650
TI  - What molars contribute to an emerging understanding of lateral enamel formation
      in Neandertals vs. modern humans.
AB  - Two hypotheses, based on previous work on Neandertal anterior and premolar teeth,
      are investigated here: (1) that estimated molar lateral enamel formation times in
      Neandertals are likely to fall within the range of modern human population
      variation, and (2) that perikymata (lateral enamel growth increments) are
      distributed across cervical and occlusal halves of the crown differently in
      Neandertals than they are in modern humans. To investigate these hypotheses,
      total perikymata numbers and the distribution of perikymata across deciles of
      crown height were compared for Neandertal, northern European, and southern
      African upper molar mesiobuccal (mb) cusps, lower molar mesiobuccal cusps, and
      the lower first molar distobuccal (db) cusp. Sample sizes range from five
      (Neandertal M(1)db) to 29 (southern African M(1)mb). Neandertal mean perikymata
      numbers were found to differ significantly from those of both modern human
      samples (with the Neandertal mean higher) only for the M(2)mb. Regression
      analysis suggests that, with the exception of the M(2)mb, the hypothesis of
      equivalence between Neandertal and modern human lateral enamel formation time
      cannot be rejected. For the M(2)mb, regression analysis strongly suggests that
      this cusp took longer to form in the Neandertal sample than it did in the
      southern African sample. Plots of perikymata numbers across deciles of crown
      height demonstrate that Neandertal perikymata are distributed more evenly across
      the cervical and occlusal halves of molar crowns than they are in the modern
      human samples. These results are integrated into a discussion of Neandertal and
      modern human lateral enamel formation across the dentition, with reference to
      issues of life history and enamel growth processes.

PMID- 18045651
TI  - Comparative observations on the tooth root morphology of Gigantopithecus blacki.
AB  - The extinct great ape Gigantopithecus blacki from the middle Pleistocene of China
      and Vietnam is known only from dental and mandibular remains, and its dietary
      specializations remain contentious. Here, for the first time, we describe the
      root morphology in G. blacki using computed tomography and three-dimensional
      image processing. We quantify the tooth root lengths and surface areas of the
      female G. blacki mandible No. 1 from the Liucheng Cave and compare it to a sample
      of extant great apes and humans, as well as the giant panda (Ailuropoda
      melanoleuca) and the American black bear (Ursus americanus). The results show
      that, in G. blacki, the pattern of mandibular root numbers-particularly that of
      the premolars-corresponds with that of Gorilla gorilla, Pan troglodytes, and
      Pongo pygmaeus. However, G. blacki can be distinguished from the extant hominids
      by having relatively higher values for postcanine root length and surface area,
      both absolutely and relative to mandibular size (except for premolar root lengths
      of humans). The relatively large postcanine root surface areas, which are most
      similar to A. melanoleuca, suggest that the dentition of G. blacki was adapted to
      sustaining relatively large occlusal forces needed to fracture mechanically
      resistant foods such as bamboo.

PMID- 18045652
TI  - Three-dimensional primate molar enamel thickness.
AB  - Molar enamel thickness has played an important role in the taxonomic,
      phylogenetic, and dietary assessments of fossil primate teeth for nearly 90
      years. Despite the frequency with which enamel thickness is discussed in
      paleoanthropological discourse, methods used to attain information about enamel
      thickness are destructive and record information from only a single plane of
      section. Such semidestructive planar methods limit sample sizes and ignore
      dimensional data that may be culled from the entire length of a tooth. In light
      of recently developed techniques to investigate enamel thickness in 3D and the
      frequent use of enamel thickness in dietary and phylogenetic interpretations of
      living and fossil primates, the study presented here aims to produce and make
      available to other researchers a database of 3D enamel thickness measurements of
      primate molars (n=182 molars). The 3D enamel thickness measurements reported here
      generally agree with 2D studies. Hominoids show a broad range of relative enamel
      thicknesses, and cercopithecoids have relatively thicker enamel than ceboids,
      which in turn have relatively thicker enamel than strepsirrhine primates, on
      average. Past studies performed using 2D sections appear to have accurately
      diagnosed the 3D relative enamel thickness condition in great apes and humans:
      Gorilla has the relatively thinnest enamel, Pan has relatively thinner enamel
      than Pongo, and Homo has the relatively thickest enamel. Although the data set
      presented here has some taxonomic gaps, it may serve as a useful reference for
      researchers investigating enamel thickness in fossil taxa and studies of primate
      gnathic biology.

PMID- 18045653
TI  - Preliminary observations on increasing root length during the eruptive phase of
      tooth development in modern humans and great apes.
AB  - Ground sections of incisors, canines, and molars were selected that showed clear
      incremental markings in root dentine. The sample comprised 98 Homo sapiens, 53
      Pan troglodytes, and a more limited combined sample of 51 Gorilla and Pongo
      sections. Daily rates of root dentine formation, together with the orientation of
      incremental markings in roots close to the cement-dentine junction (CDJ), were
      used to calculate root extension rates for the first 10mm of root formed beyond
      the buccal enamel cervix. Modern human anterior tooth roots showed a more regular
      pattern of increase in root length than those in great apes. In Pan, root growth
      rose quickly to higher rates but then flattened off. The fastest extension rates
      in modern humans were in incisor roots (10-12 microm per day), followed by
      canines (8-9 microm per day). Extension rates in Pan rose to slightly greater
      values in canines ( approximately 12-14 microm per day) than in incisors (
      approximately 10-11 microm per day). Molar tooth roots in both modern humans and
      great apes grew in a nonlinear manner. Peak rates in molars reduced from M1 to M3
      (8, 7, and 6 microm per day, respectively). Like humans, root growth in Pan
      peaked earlier in M1s at rates of between 8 and 9 microm per day, and later in
      M3s at rates of 7 to 8 microm per day. The more limited data set for Gorilla and
      Pongo molars suggests that extension rates were generally higher than in Pan by
      approximately 1.0-1.5 microm per day. There were greater differences in peak
      extension rates, with Gorilla and Pongo extension rates being between 2.5 and 4.5
      microm per day higher than those in Pan. These findings highlight for the first
      time that root growth rates differ between tooth types in both pattern and rate
      and between taxa. They provide the basis with which to explore further the
      potential comparative relationships between root growth, jaw growth, and the
      eruption process.

PMID- 18045654
TI  - Nondestructive imaging of hominoid dental microstructure using phase contrast X
      ray synchrotron microtomography.

PMID- 18045655
TI  - Dental tissue studies: 2D and 3D insights into human evolution.

PMID- 18045656
TI  - Correlation of mitochondrial superoxide dismutase and DNA polymerase beta in
      mammalian dermal fibroblasts with species maximal lifespan.
AB  - Eukaryotic cells have evolved elaborate mechanisms to preserve the fidelity of
      their genomic material in the face of chronic attack by reactive byproducts of
      aerobic metabolism. These mechanisms include antioxidant and DNA repair enzymes.
      Skin fibroblasts of long-lived mammalian species are more resistant to oxidative
      stress than those of shorter-lived species [Kapahi, P., Boulton, M.E., Kirkwood,
      T.B., 1999. Positive correlation between mammalian life span and cellular
      resistance to stress. Free Radic. Biol. Med. 26, 495-500], and we speculated that
      this is due to greater antioxidant and/or DNA repair capacities in longer-lived
      species. We tested this hypothesis using dermal fibroblasts from mammalian
      species with maximum lifespans between 5 and 122 years. The fibroblasts were
      cultured at either 18 or 3% O(2). Of the antioxidant enzymes only manganese
      superoxide dismutase was found to positively correlate with maximum lifespan
      (p<0.01). Oxidative damage to DNA is primary repaired by the base excision repair
      (BER) pathway. BER enzyme activities showed either no correlation
      (apurinic/apyrimidinic endonuclease), or correlated negatively (p<0.01) with
      donor species MLS (polymerase beta). Standard culture conditions (18% O(2))
      induced both antioxidant and BER enzymes activities, suggesting that the 'normal'
      cell culture conditions widely employed are inappropriately hyperoxic, which
      likely confounds the interpretation of studies of cellular oxidative stress
      responses in culture.

PMID- 18045657
TI  - Association of toxic and essential metals with atopy markers and ventilatory lung
      function in women and men.
AB  - The association of age, smoking, alcohol, superoxide dismutase (SOD), glutathione
      peroxidase (GPx), blood lead (BPb) and cadmium (BCd) levels, and serum levels of
      copper (SCu), zinc (SZn) and selenium (SSe) with atopic status and ventilatory
      function was examined in the groups of 166 women and 50 men with no occupational
      exposure to metals or other xenobiotics. Markers of atopy included serum total
      IgE, skin prick test (SPT) to common inhalatory allergens, non-specific nasal
      reactivity (NNR) and non-specific bronchial reactivity (NBR). Parameters of
      ventilatory function included forced vital capacity (FVC) and forced expiratory
      volume in the first second (FEV(1)). Significantly higher BPb, SZn, IgE and
      prevalence of positive SPT, and lower SCu and NNR was found in men than in women.
      Fifteen women taking female sex hormones (HT) had significantly higher SCu than
      women without HT. Regression models showed significant inverse associations
      between IgE and SCu (P=0.021) and NNR and SCu (P=0.044) in women. When excluding
      women with HT, the association of SCu and total IgE became of borderline
      significance (P=0.051), association between SCu and NNR disappeared, and
      significant positive association between total IgE and BPb emerged (P=0.046). In
      men, significant inverse association was found between positive SPT and SSe, and
      between NBR and SSe. A decrease in FVC% and FEV(1)% was associated with an
      increase in smoking intensity (P<0.001) and a decrease in SZn (P=0.043 and
      P=0.053, respectively). These results were observed at the levels of the metals
      comparable to those in general populations worldwide. The observed differences
      between men and women may partly be explained by different levels of relevant
      toxic and essential metals, and their combination. The role of female HT in
      associations of atopy markers and SCu should be further investigated.

PMID- 18045658
TI  - The use of a modelling system as a tool for air quality management: annual high
      resolution simulations and evaluation.
AB  - The high levels of air pollutants over the North-Western Mediterranean (NWM)
      exceed the thresholds set in current air quality regulations. They demand a
      detailed diagnosis of those areas where the exceedances of thresholds related to
      human health are found. In this sense, there is a need for modelling studies for
      the specific area of the NWM that take into account the annual cycle to address
      the diagnosis of air pollution. A new approach to the modelling of air quality in
      the NWM has been adopted by combining the WRF-EMICAT-CMAQ-DREAM modelling system
      to diagnose the current status of the levels of photochemical air pollution
      (focusing on ozone, O(3); nitrogen dioxide, NO(2); carbon monoxide, CO; and
      particulate matter, PM10) in the area during an annual cycle (year 2004). The
      complexity of the area of study requires the application of high spatial and
      temporal resolution (2 km and 1 h). The annual simulations need to cover the
      complex different meteorological situations and types of episodes of air
      pollution in the area of study. The outputs of the modelling system are evaluated
      against observations from 52 meteorological and 59 air quality stations belonging
      to the Environmental Department of the Catalonia Government (Spain), which
      involve a dense and accurate spatial distribution of stations in the territory
      (32,215 km(2)). The results indicate a good behaviour of the model in both
      coastal and inland areas of the NWM, with a slight trend to the overestimation of
      tropospheric O(3) concentrations and the underestimation of other photochemical
      pollutants (NO(2), CO and PM10). The modelling diagnosis indicates that the main
      air quality-related problems in the NWM are the exceedances of the 1-hr O(3)
      information threshold set in the Directive 2002/3/EC (180 microg m(-3)) as a
      consequence of the transport of O(3) precursors downwind the Barcelona Greater
      Area (BGA); and the exceedances of the annual value for the protection of human
      health for NO(2) and PM10 (40 microg m(-3), Directive 1999/30/EC), both in the
      BGA, as a consequence of the high traffic-related emissions.

PMID- 18045659
TI  - The multi-element content of the lichen Parmelia sulcata, soil, and oak bark in
      relation to acidification and climate.
AB  - Understanding how biodiversity is influenced by changing atmospheric conditions
      is important for conservation, public policy and environmental health. In a
      recent study, an impact on two of the most abundant lichens in Europe (Parmelia
      sulcata and Hypogymnia physodes) was recorded at Burnham Beeches lying 40 km west
      of London (UK) during unusual atmospheric conditions whilst other species
      remained unaffected. Bark and soil chemistry also influence lichen vitality and
      community composition. Correlations between element concentrations and element
      ratios in different samples help understand element cycling. To study this
      further, the multi-element content of the lichen P. sulcata and bark sampled in
      2000 from 16 oak (Quercus robur) trees at Burnham Beeches was compared with the
      same elements determined in 24 surface soils sampled in 2005 from beneath the
      same trees. Soil pH ranged from 4.1 to 6.7. Highly significant correlations
      (p<0.001) for Mn/Ca ratios in lichen versus bark, soil versus bark and soil
      versus lichen samples confirmed cycling via the soil-tree-lichen system. Similar
      Mn/Ca ratios were reported in coniferous forests where high Mn concentrations
      were shown to limit epiphytic lichen abundance. Soil acidification influences
      element bioavailability and bark chemistry in Burnham Beeches with implications
      for lichen diversity and health. Recovery was recorded in P. sulcata, including
      regeneration within monitoring quadrats. Biological systems are well known to be
      influenced by pollution episodes.

PMID- 18045660
TI  - A combined analysis of backward trajectories and aerosol chemistry to
      characterise long-range transport episodes of particulate matter: the Madrid air
      basin, a case study.
AB  - This study has investigated the influence of synoptic weather patterns and long
      range transport episodes on the concentration levels of airborne particulate
      matter (TSP, PM10 and PM2.5) and some major ions (SO(4)(2-), NO(3)(-) and
      NH(4)(+)) at a background rural station in central Spain. Air mass back
      trajectories arriving at the site in 1999-2005 have been analysed by statistical
      methods. First, cluster analysis was used to group trajectories into 8 clusters
      depending on their direction and speed. Meteorological scenarios associated to
      each cluster have been obtained and interpreted. Then, the incidence of different
      air mass transport patterns on particle concentrations and composition recorded
      at this station was evaluated. This evaluation included PM10 and PM2.5
      concentrations and chemical composition data, obtained at three representative
      sites of the Madrid air basin during sampling campaigns carried out in the course
      of the 1999-2005 period. Finally, a residence time analysis of trajectories was
      also performed to detect remote sources and transport pathways. Significantly
      elevated concentrations of TSP and PM10 were observed for Northern African flows
      as a consequence of the transport of mineral dust. Significant inter-cluster
      differences were also observed for PM2.5 and secondary inorganic compounds, with
      the highest concentrations associated with low baric gradient situations and
      Southern European flows. The residence time analysis confirmed that current TSP
      and PM10 concentrations in central Spain are likely to be influenced
      significantly by long-range transport of desert dust from different desert
      regions in North Africa. Furthermore, emissions from continental Europe with a
      high time of residence in the western and central areas of the Mediterranean
      basin, seem to significantly influence PM2.5 and secondary inorganic aerosol
      concentrations in this region.

PMID- 18045661
TI  - Monitoring climate at Jungfraujoch in the high Swiss Alpine region.
AB  - A homogenized temperature record measured at Jungfraujoch, the highest
      permanently manned meteorological station in Europe at 3580 m asl, is presented
      based on almost 70 years of record (1937-2005). The observed decadal variability
      as well as the overall trend (1.8 degrees C/69 years) in the homogenized data is
      comparable to other homogenized Swiss time series at other altitudes. A detailed
      analysis of seasonal mean temperature trends revealed no significant height
      dependence for the period 1961-2005. The dominant trend features are the weaker
      trends in autumn, significant only at low altitudes. Temperature indices such as
      thawing days, derived from newly homogenized minimum temperature series, exhibit
      strong vertical and seasonal trend dependence. Strongest relative trends occur in
      winter at an altitude around 1000 and 1600 m asl. For the summer season relative
      trends in thawing days are strongest at the highest stations, as expected. At
      Jungfraujoch an increase of about 50% is observed for the period 1961-2005 even
      when the extraordinary warm summer of 2003 is excluded.

PMID- 18045662
TI  - Platelet collagen receptors, signaling and antagonism: emerging approaches for
      the prevention of intravascular thrombosis.
AB  - Collagen, one of the major proteins of sub-endothelial vasculature get exposed
      following endothelium denudement, is a potent stimulator of platelet adhesion and
      aggregation. Adhesion of platelets following endothelial injury is the primary
      event usually associated with uncontrolled platelet activation culminating into
      intravascular thrombosis, thus needs to be intervened to prevent the pathology
      related to various peripheral, myocardial and cerebral ischemic episodes. Recent
      advances in the understanding of collagen mediated platelet adhesion and
      aggregation have led to the identification of two prominent receptors,
      glycoprotein Ia/IIa (GPIa/IIa or integrin alpha(2)beta(1)) and glycoprotein VI
      (GPVI) and associated intracellular signaling, which are undoubtedly the new
      emerging targets for the development of more effective antithrombotic drugs. The
      optimism for collagen antagonism is based on results obtained so far by the use
      of monoclonal and polyclonal antibodies, peptide inhibitors, knockouts models and
      collagen-mimetics in various in vitro test systems and animal models. These
      findings have revealed that collagen receptor inhibition is an attractive and
      secure strategy for the new drug development to prevent intravascular thrombosis.

PMID- 18045663
TI  - Individual propensity for thrombosis: comparison of venous and arterial
      circulations.
AB  - INTRODUCTION: The pathogenesis of venous thrombosis has been attributed to
      complex interaction between environmental and inherited variables. A basal
      predisposition for venous thrombophilia independent of environmental variables
      has not been previously defined experimentally. Both to address the existence of
      an individual propensity to venous thrombosis and to establish an animal model in
      which variables governing this propensity could be tested, we provoked venous
      thrombi in a cohort of pigs of uniform size and age. We furthermore sought to
      determine whether the thrombotic propensity in the venous circulation is
      associated with similar propensity for arterial thrombosis. MATERIALS AND
      METHODS: Bilateral iliac venous stents were deployed and 2 h later, thrombi were
      harvested and weighed. The thrombotic response was compared to carotid arterial
      thrombi generated by crush injury within the same pig. Venous and arterial
      thrombus platelet deposition were measured by scintillation detection of
      autologous (111)In-platelet content. RESULTS: In a cohort of 27 pigs, venous
      thrombus weights and platelet content varied over greater trrhan 10-fold range
      from least to greatest responders. There was strong intra-individual correlation
      of thrombus platelet deposition (r=0.86; p=0.008) and thrombus weights (r=0.68;
      p=0.015) between stented iliac vein pairs. Venous thrombosis correlated with
      whole blood platelet counts but not carotid platelet-rich thrombus formation.
      CONCLUSIONS: The wide variation in venous thrombotic response to a standardized
      injury appears to represent an intrinsic propensity of the individual. The poor
      correlation with arterial thrombosis implies unique mechanisms responsible for
      this propensity in arteries and veins.

PMID- 18045664
TI  - Comparison of prothrombin time evaluation using automated and bedside devices in
      cancer patients.

PMID- 18045665
TI  - Redirection of the reaction between activated protein C and a serpin to the
      substrate pathway.
AB  - BACKGROUND: Activated protein C (APC) reduces mortality in severe sepsis.
      Protecting APC in the circulatory system from inactivation by serine protease
      inhibitors (serpins) could improve its therapeutic efficiency. Significantly
      elevated levels of a serpin plasminogen activator inhibitor 1 (PAI-1) correlate
      with a lethal outcome in severe sepsis and disseminated intravascular
      coagulation. Intermolecular mechanisms were employed to redirect the reaction
      between APC and PAI-1 from the inhibitory to the substrate pathway, which results
      in the catalytic neutralization of the serpin. METHODS: The effects of anti-PAI-1
      monoclonal antibodies (mAbs) and vitronectin, as well as their fragments, on the
      kinetics and stoichiometry of the reaction between PAI-1 and APC were studied
      using SDS PAGE and fluorescence spectroscopy. RESULTS: MAbs with epitopes at
      alpha-helix F redirected 70-80% of the reaction between PAI-1 and APC, to the
      substrate pathway. Vitronectin and its SMB domain did not affect the
      stoichiometry of acyl-enzyme formation, but enhanced the effect of mAbs. While
      vitronectin induced a more than two-fold increase in the rate of the reaction
      between PAI-1 and APC, neither mAbs (mAb fragments), nor SMB domain of
      vitronectin affected it. CONCLUSIONS: Ligands interacting with alpha-helix F of
      PAI-1 demonstrated a potential for the protection of APC from inactivation by PAI
      1. Since the mechanism of proteinase/serpin interaction is universal, a similar
      design and approach could be employed for enhancing the inactivation of other
      serpins in order to preserve APC activity in the circulation. Rational
      pharmacological targeting of the inhibitors of APC could have therapeutic
      utility.

PMID- 18045666
TI  - Incidence, risk factors and consequences of portal vein and systemic thromboses
      in hepatocellular carcinoma.
AB  - INTRODUCTION: Hemostatic activation may be important for tumor biology.
      Hepatocellular carcinoma (HCC) is commonly associated with portal vein thrombosis
      (PVT). Little is known about factors predictive for PVT in patients with HCC or
      its correlation with systemic venous thromboembolism (VTE). METHODS: We conducted
      a retrospective chart review of 194 consecutive patients diagnosed with HCC at
      the University of Rochester between 1998 and 2004 to identify the frequency and
      risk factors for PVT and its correlation with VTE and survival. RESULTS: Sixty
      patients (31%) had PVT with a higher rate in the non-transplant group compared to
      transplanted patients (34% vs. 24%; p=0.15). In multivariate analysis, Child
      Turcotte Pugh (CTP) class, stage, major vessel involvement, serum albumin, and
      serum AFP were independently associated with PVT (p<0.05 for each). The presence
      of PVT was associated with reduced survival (median survival 2.3 months for those
      with PVT versus 17.6 months for those without PVT, HR 2.05, p=0.004). The
      incidence of systemic VTE in the total population was 6.7%, and patients with PVT
      had a higher rate of systemic VTE compared to patients without PVT (11.5% vs.
      4.4%; p=0.04). CONCLUSION: PVT is common in patients with HCC, indicates advanced
      disease, is associated with worse survival and correlates with systemic VTE,
      suggesting a common mechanism of hemostatic activation. Advanced stage, higher
      CTP class, major vessel involvement, low serum albumin, and high AFP levels are
      predictive of PVT in patients with HCC.

PMID- 18045667
TI  - Linear diffusion of thrombin and factor Xa along the heparin molecule explains
      the effects of extended heparin chain lengths.
AB  - QUESTION: How does the size of the heparin moiety in the anti-thrombin (AT)
      heparin complex influence its anticoagulant properties? APPROACH: Of 52 heparin
      fractions of precise Mr between 2800 and 37,000 we determined the dissociation
      constant (Kd) of the binding of the enzyme to the AT-heparin complex and the
      decay constant (kdec) of thrombin and factor Xa at 1 microM of that complex.
      RESULTS: The Kd of thrombin or factor Xa is constant when expressed in terms of
      the concentration of sugar units, i.e. the enzymes bind the better the longer the
      heparin. Thrombin (Kd=1.86+/-0.13 microM) binds 11 times tighter than factor Xa
      (Kd=20.2 +/-1.5 microM). Factor Xa inactivation velocity is proportional to the
      concentration of pentasaccharide-bound AT if Mr<10,000 but decreases at higher
      Mr. Thrombin inactivation is constant per pentasaccharide with twelve adjacent
      monosaccharides (C-domain). CONCLUSION: The data fit a model in which thrombin
      and factor Xa bind at a random site on the heparin chain and, via one-dimensional
      diffusion, reach the AT that is bound to its specific binding site on the
      heparin. Factor Xa, but not thrombin, can dissociate from heparin before reaching
      bound AT.

PMID- 18045668
TI  - Additional evidence for anxiolytic- and antidepressant-like activities of
      saredutant (SR48968), an antagonist at the neurokinin-2 receptor in various
      rodent-models.
AB  - Central tachykinins have been shown to play a role in the modulation of stress
      related behaviours. Saredutant, a tachykinin NK2 receptor antagonist, displayed
      mixed anxiolytic- and antidepressant-like activities in rodents. The present
      study aimed at further characterizing its psychotropic properties. Saredutant was
      tested in the rat social interaction test to further confirm its anxiolytic-like
      activity, and in a variety of behavioural models sensitive to antidepressant
      drugs. In the rat social interaction test, saredutant (20 mg/kg, i.p.)
      significantly increased the time spent in interaction, as did the prototypical
      anxiolytic agents, diazepam (1 mg/kg, i.p.) and buspirone (1 mg/kg, s.c.), but
      not the antidepressant, fluoxetine. In a differential reinforcement of low rate
      72s task, saredutant (3 mg/kg, i.p.) displayed an antidepressant-like activity by
      increasing reinforced response rate and percentage of responses emitted in the
      inter-response time bin [49-96 s]. In bulbectomized rats, saredutant (20 mg/kg,
      i.p.) restored the deficit of acquisition of passive avoidance. In rat pups
      separated from their mother, saredutant (3-10 mg/kg, s.c.) reduced ultrasonic
      distress calls. Finally, in the chronic mild stress paradigm in mice, a 29-day
      treatment regimen with saredutant (10 mg/kg, i.p.) attenuated stress-induced
      physical degradation. Importantly, in the depression models, the effects of
      saredutant were comparable to those obtained under similar experimental
      conditions by reference antidepressants such as fluoxetine or imipramine.
      Together, these results suggest further that the NK2 receptor may represent an
      attractive target for the treatment of both depressive and anxiety disorders.

PMID- 18045669
TI  - Free tryptophan/large neutral amino acids ratios in blood plasma do not predict
      cerebral spinal fluid tryptophan concentrations in interleukin-1-induced
      anorexia.
AB  - Peripheral administration of interleukin-1 (IL-1) reduces food intake and affects
      brain serotonergic activity, suggesting a causal relationship. Furthermore, IL-1
      increases the brain concentrations of the serotonin precursor, tryptophan (TRP),
      by unclear mechanism(s). We aimed at confirming the link between IL-1
      administration, raised brain TRP concentrations and the development of anorexia,
      and at investigating the mechanisms of TRP entry into the brain. Thirty adult,
      overnight fasted Sprague-Dawley rats were randomly assigned to i.p. injections of
      1 mug/kg BW of IL-1 alpha (n=10) or vehicle (n=10), or to pair-feeding with IL-1
      animals (n=10). After 2 h, food intake, blood plasma concentrations of total TRP,
      free TRP, large neutral amino acids (LNAA; competing with TRP for brain entry)
      were measured. Cerebral spinal fluid (CSF) TRP concentrations were also measured.
      TRP brain availability was assessed by calculating the plasma ratio free
      TRP/LNAA. Following IL-1 injection, food intake significantly declined in IL-1
      rats, which was paralleled by decreased plasma free TRP and increased plasma
      LNAA. Despite a decrease in the free TRP/LNAA ratios in plasma, IL-1
      significantly increased concentrations of TRP in CSF. These data show that the
      acute peripheral administration of IL-1 induces anorexia and raises CSF TRP
      levels. Considering the possible role of the raised CSF TRP in influencing brain
      serotonin activity, it is postulated that increased serotonergic
      neurotransmission could be involved in IL-1 induced anorexia.

PMID- 18045670
TI  - Application of long-term microdialysis in circadian rhythm research.
AB  - Our laboratory has pioneered long-term microdialysis to monitor pineal melatonin
      secretion in living animals across multiple circadian cycles. There are numerous
      advantages of this approach for rhythm analysis: (1) we can precisely define
      melatonin onset and offset phases; (2) melatonin is a reliable and stable
      neuroendocrine output of the circadian clock (versus behavioral output which is
      sensitive to stress or other factors); (3) melatonin measurements can be
      performed extremely frequently, permitting high temporal resolution (10 min
      sampling intervals), which allows detection of slight changes in phase; (4) the
      measurements can be performed for more than four weeks, allowing perturbations of
      the circadian clock to be followed long-term in the same animals; (5) this is an
      automated process (microdialysis coupled with on-line HPLC analysis), which
      increases accuracy and bypasses the labor-intensive and error-prone manual
      handling of dialysis samples; and (6) our approach allows real-time investigation
      of circadian rhythm function and permits appropriate timely adjustments of
      experimental conditions. The longevity of microdialysis probes, the key to the
      success of this approach, depends at least in part on the methods of the
      construction and implantation of dialysis probes. In this article, we have
      detailed the procedures of construction and surgical implantation of
      microdialysis probes used currently in our laboratory, which are significantly
      improved from our previous methods.

PMID- 18045671
TI  - A top-down perspective on dopamine, motivation and memory.
AB  - Dopamine (DA) activity, in the form of increased neural firing or enhanced
      release of transmitter from nerve terminals and varicosities, is linked to a
      number of important psychological processes including: movement; hedonic
      reactions to positive reward; provision of an error detection signal during the
      acquisition of new learning; response to novel stimuli; provision of
      reinforcement signals essential for acquisition of new action patterns; and
      incentive motivation. This review focuses primarily on our research linking
      dynamic changes in DA efflux on the timescale of minutes, with incentive
      motivation, as revealed by brain dialysis experiments in behaving animals. Recent
      experiments on sensory-specific satiety and successive positive and negative
      contrast are discussed along with the distinction between preparatory behaviors
      that precede contact with biologically significant stimuli and subsequent
      consummatory behaviors. The relationship between DA efflux in the medial
      prefrontal cortex (mPFC) and foraging for food based on working memory is also
      discussed in support of the conjecture that DA may serve as a link between
      motivation and memory functions. Evidence in support of 'top-down' regulation of
      dopaminergic activity in the mesocorticolimbic DA pathways is reviewed briefly to
      introduce a mechanism by which activation of ascending DA projections in this
      manner might optimize dopaminergic modulation of executive function within
      regions such as the mPFC. Collectively, these processes could ensure coordination
      between cognitive processes that assess current opportunities and the
      motivational systems that select and engage patterns of approach behavior that
      bring organisms into contact with the essentials for survival.

PMID- 18045672
TI  - Noradrenergic antagonism enhances the conditioned aversive effects of cocaine.
AB  - The propensity to self-administer cocaine may be a function of both its
      positively reinforcing and aversive effects, with the latter acting as a limiting
      factor on overall drug taking. However, relative to what is known about the
      physiological underpinnings of cocaine's positively reinforcing effects, little
      is known about its aversive effects. There is some evidence that cocaine's
      aversive effects, as indexed in the conditioned taste aversion (CTA) preparation,
      are catecholaminergically mediated, i.e., through cocaine's actions on the
      dopaminergic and noradrenergic neurotransmitter systems. Although limited
      evidence suggests a role for dopamine, there has yet to be a direct assessment of
      noradrenergic involvement. To better characterize a role for this system, cocaine
      induced CTAs (10, 18 and 32 mg/kg) were conducted under conditions of antagonism
      at the norepinephrine alpha(1) and beta receptors using prazosin (0.3 mg/kg;
      Experiment 2) and propranolol (10 mg/kg; Experiment 3), respectively, at doses
      that were determined to be non-aversive (Experiment 1). In each case of
      noradrenergic antagonism, CTAs with cocaine were not attenuated, suggesting that
      this drug's conditioned aversive effects are mediated by non-noradrenergic NT
      activity. Furthermore, prazosin and propranolol administration appeared to
      facilitate the conditioned aversive effects of cocaine. The implications of these
      findings in regards to other neurochemical processes are discussed.

PMID- 18045673
TI  - Factors affecting plasma progesterone in the early fetal period in high producing
      dairy cows.
AB  - The aim of the present study was to determine whether certain animal- or
      management related factors could affect plasma progesterone concentrations on Day
      42 of gestation in high producing dairy cows. Factors affecting early fetal loss
      were also analyzed. The study population was comprised of 199 pregnant cows
      classified as having high (> or =9 ng/ml) or low (<9 ng/ml) plasma progesterone
      concentrations. Through logistic regression procedures it was determined that,
      based on the odds ratio, cows with two or more corpora lutea were three times
      more likely to have high progesterone concentrations than cows with a single
      corpus luteum. Low producing cows during the warm season were 2.86 times more
      likely to have high progesterone concentrations than the remaining cows.
      Primiparous cows with high concentrations (>4 ng/ml) of pregnancy associated
      glycoprotein-1 (PAG-1) were 2.73 times more likely to have high progesterone
      concentrations than the remaining cows. Of the 199 pregnancies, 25 (12.6%)
      suffered early fetal loss: 22/136 (16.2%) during the warm season and 3/63 (4.8%)
      during the cool season, all in cows without additional corpora lutea. Based upon
      the odds ratio, cows without an additional corpus luteum were 3.67 times more
      likely to suffer fetal loss during the warm season than during the cool season.
      Our results indicate that milk production, the presence of two or more corpora
      lutea and plasma PAG-1 concentrations can affect plasma progesterone
      concentrations at the onset of the fetal period. The presence of an additional
      corpus luteum strongly diminished the risk of early fetal loss during the warm
      period.

PMID- 18045674
TI  - Melatonin administration increased plasminogen activator activity in ram
      spermatozoa.
AB  - The aim of the present study was to investigate the effect of melatonin on
      plasminogen activator activity (PAA), plasminogen activator inhibition (PAI) and
      plasmin inhibition (PI) in ram spermatozoa and seminal plasma, in correlation
      with changes in blood testosterone. Melatonin implants (18 mg) were placed
      subcutaneously in sixteen Chios rams in autumn and spring. Semen samples for
      spectrophotometrical assays were collected 36 h before the implantation of
      melatonin and thereafter once a week, for 17 weeks. Blood samples for
      testosterone assay (RIA) were collected 8h before implantation (one sample/30 min
      x 7.5 h) and thereafter every 15 days for 105 days after implantation. For each
      ram, six parameters of testosterone were estimated: mean value, basal level,
      number of peaks, peak amplitude, peak duration and mean testosterone
      concentration during peaks. Melatonin implantation during autumn induced an
      increase in PAA and t-PAI in spermatozoa; melatonin implantation in spring
      induced an additional increase in u-PAI and PI; no change in PAA, PAI or PI was
      found in seminal plasma, during autumn or spring. The melatonin-induced increase
      of PAA, PAI and PI in spermatozoa was in positive correlation with the increase
      of testosterone mean value, basal level and number of peaks; the increase of
      testosterone parameters was greater in autumn compared to spring. Changes of PAA,
      PAI and PI of spermatozoa, under the influence of melatonin, might indicate
      changes in the fertilizing ability of spermatozoa, since plasminogen activators
      and their inhibitors are present on the plasma and the outer acrosomal membrane
      of spermatozoa and are released during the acrosome reaction.

PMID- 18045675
TI  - Oxidative mechanisms in the pathogenesis of alcoholic liver disease.
AB  - Although the capacity of ethanol to induce oxidative stress in the liver is well
      established, the mechanisms by which oxidative damage contributes to the
      pathogenesis of alcoholic liver disease (ALD) is still incompletely understood.
      Recent reports have implicated oxidative mechanisms in the onset of alcoholic
      steatosis and in the formation of Mallory's bodies. Moreover, by inducing
      mitochondrial alterations, oxidative stress promotes hepatocyte necrosis and
      contributes to alcohol-induced sensitization of hepatocyte to the pro-apoptotic
      action of TNF-alpha. Oxidative mechanisms play also a role in the progression of
      liver fibrosis by triggering the release of pro-fibrotic cytokines and activating
      collagen gene expression in hepatic stellate cells. Finally, immune responses
      towards antigens originating from the reactions of lipid peroxidation products
      with hepatic proteins might represent one of the mechanisms that contribute to
      perpetuate chronic hepatic inflammation in ALD. Altogether these observations
      give a rationale to the possible clinical application of antioxidants in the
      therapy of ALD.

PMID- 18045676
TI  - WITHDRAWN: A novel molecular mechanism to account for the action of rifampicin
      against arthritis.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 18045677
TI  - Effect of different photo-activation methods on push out force, hardness and
      cross-link density of resin composite restorations.
AB  - OBJECTIVES: To evaluate push out force, hardness and cross-link density (CLD) of
      composite restorations photo-activated by different methods. METHODS: Z250 (3M
      ESPE) and XL2500 halogen unit (3M ESPE) were used. For push out force and
      hardness tests, conical restorations were made in bovine incisors. For CLD
      evaluation, cylindrical specimens were prepared. Different activation methods
      were tested: high-intensity continuous (HIC), low-intensity continuous (LIC),
      soft-start (SS) or pulse-delay (PD), with constant radiant exposure. Knoop
      readings were performed on bottom and top surfaces. Data were submitted to two
      way ANOVA and Tukey's test (alpha=0.05). Push out force data were submitted to
      ANOVA and Tukey's test (alpha=0.05). Failure modes were classified under
      magnification (40x). CLD was estimated by hardness readings before and after
      storage in ethanol. Data were submitted to RM-ANOVA and Tukey's test
      (alpha=0.05). RESULTS: No significant differences in top hardness (KHN, N/mm2)
      were observed for HIC (598), LIC (564), SS (585) and PD (573). LIC presented
      significantly lower bottom hardness (520) than HIC (574), SS (562) and PD (572).
      Push out force (N) for SS (246) and PD (238) were similar, but significantly
      higher compared to LIC (198) and HIC (193). For HIC and LIC, only adhesive and
      mixed failures were observed. For SS and PD, cohesive failures also occurred.
      After storage, HIC and LIC presented significantly lower softening than PD. HIC
      also presented lower softening than SS, and similar results were observed for SS
      and PD. SIGNIFICANCE: Different activation methods can interfere with push out
      force, hardness and CLD of composite restorations.

PMID- 18045678
TI  - Measurement of microstrains across loaded resin-dentin interfaces using
      microscopic moire interferometry.
AB  - Little is known about the mechanical behavior of resin-dentin interfaces during
      loading. The presence of relatively compliant hybrid and adhesive layers between
      stiffer dentin and resin composite should deform more during compressive loading.
      OBJECTIVE: The objective of this study was to measure changes in microstrain
      across bonded dentin interfaces in real time using a recently developed
      microscope moire interferometer. METHOD: This system used a miniature moire
      interferometer, using two CCD cameras for simultaneous recording of longitudinal
      and transverse deformation fields, a piezotransducer for fringe shifting and use
      of a microscope objective with magnification up to 600 x. Small beams (1 mm x 2
      mm x 6 mm) of moist resin-bonded dentin covered with cross-lined diffraction
      grating replica were placed in a miniature compression tester to allow controlled
      loading from 2 to 37 N while imaging the interference fringe patterns. RESULTS:
      Resin-dentin interfaces created by bonding dentin with Single Bond/Z100, under
      compressive loading, exhibited comparatively large strains across the adhesive
      hybrid interface. When the wrapped phase maps were unwrapped to permit conversion
      of fringe order to displacements, the 2-D profiles of strain fields revealed non
      uniform strains across the adhesive interface. In the adhesive/hybrid layer zone,
      the negative strain was larger (i.e. -6000 mu epsilon) than that seen in the
      adjacent resin composite or underlying mineralized dentin. The changes were
      elastic because they disappeared when the load was removed. SIGNIFICANCE:
      Microscopic moire interferometry can be very useful in revealing real-time strain
      across bonded interfaces under load.

PMID- 18045679
TI  - Effects of water content and initiator composition on photopolymerization of a
      model BisGMA/HEMA resin.
AB  - AIMS: The purpose of this study was to evaluate the effects of photoinitiator
      type and water content on the polymerization rate (Rp) and degree of conversion
      (DC) of a model BisGMA/HEMA-based resin. MATERIALS AND METHODS: The comonomer
      mixture consisted of BisGMA/HEMA (60/40 by weight). Different two- or three
      component photoinitiator systems were incorporated. Two-component systems were
      0.5% CQ (camphorquinone) and 0.5% DMAEMA (2-(dimethylamino) ethyl methacrylate)
      or 0.5% CQ and 0.5% 4E (ethyl 4-dimethylaminobenzoate). The three-component
      systems were added 1% DPIHP (diphenyliodonium hexafluorophosphate) to the above
      systems. Each system was tested as made, or after addition of 5, 10, 15wt% water.
      When cured under a conventional dental light, the Rp and DC of each formulation
      was determined using time-resolved attenuated total reflection (ATR)-Fourier
      transform infrared (FTIR) spectroscopy. RESULTS: For mixtures containing two
      component initiator systems, when the hydrophobic initiator CQ was used in
      combination with hydrophilic DMAEMA, Rps and DCs were dramatically decreased as a
      function of water content. The Rps and DCs of the hydrophobic CQ/4E system were
      higher than those of the CQ/DMAEMA system in the presence of water. For three
      component initiator systems, incorporation of DPIHP enhanced the polymerization
      of all mixtures in the presence of water compared to their counterpart two
      component initiators. Interestingly, the CQ/DMAEMA caused greater DC and Rp when
      DPIHP was used. SIGNIFICANCE: The hydrophobicity/hydrophilicity of photoinitiator
      components significantly affects both the DC as well as Rp when in the presence
      of water. The results indicate that formulation of photoinitiator components
      should be based on the effectiveness of the bonding systems under both dry and
      wet conditions.

PMID- 18045680
TI  - Sol-gel materials 2. Light-curing dental composites based on ormocers of cross
      linking alkoxysilane methacrylates and further nano-components.
AB  - OBJECTIVES: The objective of this study was to investigate the use of ormocers,
      which were synthesized from amine or amide dimethacrylate trialkoxysilanes.
      Ormocers showed improved biocompatibility in dimethacrylate-diluent-free
      composite restoratives. Selected mechanical properties, such as flexural strength
      and flexural modulus of experimental composites containing ormocers were
      investigated. In addition, the influence of methacrylate-substituted ZrO2
      clusters and SiO2 organosols on the mechanical properties of composites was
      studied. METHODS: The flexural strength and flexural modulus of elasticity were
      determined according to ISO 4049: 2000. For this purpose, test specimens
      (2mmx2mmx25mm) of the composites investigated were prepared in stainless steel
      moulds and light-cured (150mW/cm2, 2x180s). The flexural strength and flexural
      modulus of elasticity were measured after the samples had been stored in water
      for 24h at 37 degrees C. RESULTS: While visible light-cured dimethacrylate
      diluent-free composite restoratives based on the investigated ormocers showed a
      similar flexural strength and flexural modulus of elasticity compared to
      composites that contain only dimethacrylates, their double bond conversion was
      considerable lower. The simultaneous addition of methacrylate-substituted ZrO2
      clusters and SiO2 organosols to the ormocer composite improved the mechanical
      properties of the composites. SIGNIFICANCE: Ormocers of amine or amide
      dimethacrylate trialkoxysilanes enabled the preparation of dimethacrylate-diluent
      free composite restoratives. Based on the lower cytotoxicity of the ormocers, the
      prepared restorative composites should show improved biocompatibility. With the
      addition of nanoparticles, such as methacrylate-substituted ZrO2 clusters or SiO2
      organosols, the mechanical properties of composites can be improved.

PMID- 18045681
TI  - Global health and Japan's foreign policy.

PMID- 18045682
TI  - Managing risk: identifying environmental causes of disease.

PMID- 18045683
TI  - In situ IGF-1 gene delivery to cells emerging from the injured anterior cruciate
      ligament.
AB  - Ruptures of the anterior cruciate ligament (ACL) are common knee injuries that do
      not heal, even with surgical repair. Our research is directed towards developing
      novel, biological approaches that enable suture repair of this ligament. One
      promising strategy involves the insertion of a collagen hydrogel between the
      severed ends of the ACL. Cells migrate from the damaged ligament into the
      hydrogel and produce repair tissue. Here we have investigated the potential for
      augmenting this process by the transfer of insulin like growth factor (IGF) 1
      cDNA to the repair cells using an adenovirus vector. The goal is to achieve
      direct, in situ gene delivery by loading the hydrogel with vector prior to its
      insertion into the defect. In a step-wise approach towards evaluating this
      process, we confirmed that monolayers of ACL fibroblasts were efficiently
      transduced by adenovirus vectors and continued to express transgenes when
      subsequently incorporated into the hydrogel; indeed, transgene expression
      persisted longer within collagen gels than in monolayer culture. Transfer of IGF
      1 cDNA increased the cellularity of the gels and led to the synthesis and
      deposition of increased amounts of types I and III collagen, elastin, tenascin,
      and vimentin. The cells remained viable, even when subjected to high viral loads.
      Similar results were obtained when collagen hydrogels were preloaded with
      adenovirus prior to insertion into an experimental ACL lesion in vitro. These
      data confirm the promise of using vector-laden hydrogels for the in situ delivery
      of genes to cells within damaged ligaments and suggest novel possibilities for
      the biological repair of the ACL.

PMID- 18045684
TI  - Enhancement of bone-bonding ability of bioactive titanium by prostaglandin E2
      receptor selective agonist.
AB  - Systemic administration of prostaglandin E2 receptor (EP4) selective agonist
      increases both bone formation and resorption, and consequently leads to an
      increase in bone mass. Although previous studies have reported that EP4 agonist
      enhanced bone remodeling and fracture healing, it was not known if EP4 agonist
      activates the bone-biomaterial interface. Bioactive titanium prepared by chemical
      and thermal treatment can bond to living bone and is suitable for use in clinical
      applications in cementless fixation devices. Therefore, we examined whether the
      administration of EP4 agonist enhances the bonding strength between bone and
      bioactive titanium. Bioactive titanium plates were inserted into the tibia bone
      of rabbits and examined histologically and biomechanically at 4, 8, and 16 weeks.
      EP4 agonist was administrated systemically every 2 weeks after surgery. A non
      administrated control group, a low-dose group (10 microg/kg body weight (BW)),
      and a high-dose group (100 microg/kg BW) were compared. The bonding strength of
      bioactive titanium in the EP4 agonist groups was significantly higher than that
      in the control group at both 4 and 8 weeks, and enhanced bone remodeling and
      direct bonding around the bioactive titanium plates was observed only in the EP4
      agonist groups at 4 weeks. EP4 agonist enhanced bone formation around the
      bioactive titanium plate, and achieved early direct bone bonding.

PMID- 18045685
TI  - Alginate-based microencapsulation of retinal pigment epithelial cell line for
      cell therapy.
AB  - The goals of this study were to evaluate human retinal pigment epithelial cell
      line (ARPE-19) for cell encapsulation and to optimize the alginate-based
      microencapsulation. We used immortalized ARPE-19 cells and the transfected sub
      line that expresses secreted alkaline phosphatase (SEAP) reporter enzyme.
      Alginate was cross-linked with different divalent cations (Ca(2+), Ba(2+), Sr(2+)
      and combination of Ca(2+) and Ba(2+)), coated first with poly-l-lysine (PLL), and
      then with alginate. Microcapsules with different pore sizes and stability were
      generated. The pore size of the microcapsules was assessed by the release of
      encapsulated fluorescein isothiocyanate (FITC)-dextrans. The viability of the
      cells in the microcapsules was studied in vitro by assessing the secretion rates
      of SEAP and oxygen consumption by the cells. The best microcapsule morphology,
      durability and cellular viability were obtained with alginate microcapsules that
      were cross-linked with Ca(2+) and Ba(2+) ions and then coated with PLL and
      alginate. Based on FITC-dextran release these microcapsules have porous wall that
      enables the rapid contents release. The ARPE-19 cells maintained viability in the
      Ca(2+) and Ba(2+) cross-linked microcapsules for at least 110 days. The alginate
      microcapsules cross-linked with Ca(2+) and Ba(2+) have sufficiently large pore
      size for prolonged cell viability and for the release of secreted SEAP model
      protein (Mw 50 kDa; radius of gyration of 3 nm). ARPE-19 cells show long-term
      viability and protein secretion within alginate microcapsules cross-linked with
      Ca(2+) and Ba(2+). This combination may be useful in cell therapy.

PMID- 18045686
TI  - Hypothermia-induced increase in galanin concentrations and ischemic
      neuroprotection in the rat brain.
AB  - The effects of hypothermia on galanin concentrations and the relation between
      ischemic brain lesions, hypothermia and galanin concentrations in a transient and
      focal rat stroke model were investigated in order to elucidate whether
      hypothermia-induced alterations in galanin concentrations could constitute a part
      of the established neuroprotective effect of hypothermia. Female rats were
      allocated to normothermia (37 degrees C) or hypothermia (33 degrees C) treatments
      during a 60 min microclip middle cerebral artery occlusion. The ischemic lesions
      were visualized after observation periods of 2 or 7 days and the concentration of
      galanin measured by radioimmunoassay in extracts of punch biopsies from both the
      lesioned and the contralateral control hemisphere. Hypothermia-induced an overall
      increase in the concentrations of immunoreactive galanin (p<0.001). The elevated
      galanin levels were predominantly found in the non-ischemic control hemisphere,
      in the hippocampus, thalamus and the posterior part of parietal cortex. The
      galanin concentrations were lower in the ischemic hemisphere in both the normo-
      and hypothermic animals compared to the corresponding contra lateral intact
      hemisphere (p=0.049). The factor of time, 2 respectively 7 days, did not show any
      significant difference regarding the galanin concentrations (p=0.844).
      Multivariate analyses of variance revealed significant effect of ischemia on the
      size of the ischemic brain lesions (p=0.001) but no overall effect of temperature
      when data from both 2 and 7 days observation periods were analyzed together. The
      ischemic lesions were generally larger at 33 degrees after 2 days (p=0.230).
      Prolonged observation time of 7 days resulted in a significant reduction of the
      ischemic brain lesion (p=0.011) with smaller ischemic lesions in the hypothermic
      group. Our data support the notion that hypothermia-induced increase in the
      tissue concentrations of galanin in the brain are the result of changes from
      optimal homeostatic conditions - the hypothermia-induced stress - rather than the
      ischemia/re-perfusion lesion induced changes in galanin concentrations.
      Hypothermia-induced elevation in galanin concentration is therefore not likely to
      be amongst the major protective mechanisms of hypothermia.

PMID- 18045687
TI  - FACIT collagen (1alpha-chain) is expressed by hemocytes and epidermis during the
      inflammatory response of the ascidian Ciona intestinalis.
AB  - Based on previous cloning and sequencing study, real-time PCR and in situ
      hybridization assays of the inflamed body wall of LPS-injected Ciona intestinalis
      showed the enhanced gene expression of a collagen with FACIT structural features
      (Ci-type IX-Col 1alpha-chain). By using specific antibodies raised against an
      opportunely chosen Ci-type IX-Col synthetic peptide, the fibroblast property of
      hemocytes challenged in vitro with LPS (at 4h) was displayed by flow cytometry,
      while immunocytochemistry identified hemocytes with large granules (morula cells)
      as collagen-producing cells. Hemocyte lysate supernatant analyzed in
      immunoblotting contained a 60 kDa band identifiable as 1alpha-chain-Ci-type IX
      Col. Observations of body wall sections (immunohistochemistry method) supported
      the role of hemocytes and showed that epidermis expressed Ci-type IX-Col 1alpha
      chain in the time course of the inflammatory reaction (within 24h). Transcript
      and protein were mainly found in the epidermis that outlined the proximal side of
      the tunic matrix (at 24h after LPS injection), in cells associated with the
      epidermis at 4 and 192 h. In conclusion, the C. intestinalis inflammatory
      response to LPS challenge appeared to be composed of a complex reaction set, and
      for the first time we showed in ascidians a granulation tissue with FACIT
      collagen production that could participate in inflammation and wound healing.
      Like in vertebrates, C. intestinalis acute inflammatory reactions result in a
      regulated pattern of tissue repair with collagen expression during remodelling.
      Ci-type IX-Col could be involved in a network of non-fibril-forming collagens
      that participates in the organization of extracellular matrix and defense
      responses.

PMID- 18045688
TI  - Immune responses of mussel hemocyte subpopulations are differentially regulated
      by enzymes of the PI 3-K, PKC, and ERK kinase families.
AB  - Various hemocyte cell types have been described in invertebrates, but for most
      species a functional characterization of different hemocyte cell types is still
      lacking. In order to characterize some immunological properties of mussel
      (Mytilus galloprovincialis) hemocytes, cells were separated by flow cytometry and
      their capacity for phagocytosis, production of reactive oxygen species (ROS), and
      production of nitric oxide (NO), was examined. Phosphatidylinositol 3-kinase (PI
      3-K), protein kinase C (PKC), and extracellular signal-regulated kinase (ERK)
      inhibitors were also used to biochemically characterize these cell responses.
      Four morphologically distinct subpopulations, designated R1-R4, were detected.
      R1, R2, and R3 cells presented different levels of phagocytosis towards zymosan,
      latex beads, and two bacteria species. Similarly, R1 to R3, but not R4, cells
      produced ROS, while all subpopulations produced NO, in response to zymosan.
      Internalization of all phagocytic targets was blocked by PI 3-K inhibition. In
      addition, internalization of latex particles, but not of bacteria, was partially
      blocked by PKC or ERK inhibition. Interestingly, phagocytosis of zymosan was
      impaired by PKC, or ERK inhibitors, only in R2 cells. Zymosan-induced ROS
      production was blocked by PI 3-K inhibition, but not by PKC, or ERK inhibition.
      In addition, zymosan-stimulated NO production was affected by PI 3-K inhibition
      in R1 and R2, but not in R3 or R4 cells. NO production in all cell types was
      unaffected by PKC inhibition, but ERK inhibition blocked it in R2 cells. These
      data reveal the existence of profound functional and biochemical differences in
      mussel hemocytes and indicate that M. galloprovincialis hemocytes are specialized
      cells fulfilling specific tasks in the context of host defense.

PMID- 18045689
TI  - Cutaneous antibody-secreting cells and B cells in a teleost fish.
AB  - Antibodies in cutaneous mucus and skin of teleosts play a critical role in the
      protective immune response against infection. We demonstrate by ELISPOT that
      antibody-secreting cells (ASC), which include LPS-inducible B cells
      (plasmablasts) and non-replicating plasma cells, reside in low numbers in the
      skin of channel catfish. Following immunization against the protozoan parasite
      Ichthyophthirius multifiliis, which infects skin and gills, the number of ASC in
      skin increased 20-fold, indicating that the number of ASC in skin is dynamic and
      increases in response to parasite infection. The number of ASC in skin remained
      elevated for at least 17 weeks after the last parasite exposure. Cutaneous ASC
      included I. multifiliis-specific ASC, which undoubtedly serve as the primary
      source of cutaneous antibodies that confer long-term humoral immunity against
      reinfection. Our demonstration that skin contains B cells and plasma cells
      suggests that it is an integral component of the teleost immune system.

PMID- 18045690
TI  - Ten years later: Locating and interviewing children of drug abusers.
AB  - Longitudinal studies require high follow-up rates in order to maintain
      statistical power, reduce bias, and enhance the generalizability of results. This
      study reports on locating and survey completion for a 10-year follow-up of the
      Focus on Families project, an investigation of 130 families headed by parents who
      were enrolled in methadone treatment for opiate addiction. Despite having no
      contact with participants in the study for at least 10 years, the project
      successfully located nearly 99% of parent participants and 98% of their children.
      Twenty-four percent of the parents and one child had died before the follow-up.
      Of the surviving sample, 91% of parents and 86% of the children completed the
      follow-up interview. Multiple techniques were used to locate study participants,
      including internet searches, researching court and public records, collaborating
      with government and service agencies, and contacting family and social networks.
      For more than half of the sample, costly efforts were required to locate
      individual participants.

PMID- 18045691
TI  - Physical activity in infants with Down syndrome receiving a treadmill
      intervention.
AB  - Despite the recognized relevance of physical activity in the development and
      health of children, assessment of physical activity levels (PA-level) in infancy
      is limited, especially in infants with Down syndrome (DS). Increasing PA-level
      using a treadmill training (TMT) intervention may benefit infants with motor
      delays. The purpose of this study was to investigate whether a higher intensity,
      individualized TMT protocol (HI) would elicit immediate and short-term higher PA
      level in infants with DS than a lower intensity, generalized training protocol
      (LG). Thirty infants with DS were randomly assigned to the LG or the HI group.
      Training was terminated when the infants could walk three steps independently.
      Activity monitors were placed on infants' trunks and legs for a 24-h period every
      other month during the intervention phase, and at set intervals 1-year post
      independent walking onset. Data were analyzed to separate sedentary-to-light
      activity (Lowact) and moderate-to-vigorous activity (Highact). Overall our
      results demonstrate that infants receiving the HI TMT had higher levels of
      Highact than infants in the LG group, factoring out the activity produced by the
      intervention itself. Infants in the LG group spent more time in Lowact than the
      HI group. In addition, these results seemed to be retained during the post
      intervention follow-up. Despite these exciting results, more work is needed to
      understand the relationship of the intensity of TMT on PA-level in infants with
      DS, and whether PA-level and TMT are related to motor milestone achievement
      and/or health benefits.

PMID- 18045693
TI  - Automated video-based facial expression analysis of neuropsychiatric disorders.
AB  - Deficits in emotional expression are prominent in several neuropsychiatric
      disorders, including schizophrenia. Available clinical facial expression
      evaluations provide subjective and qualitative measurements, which are based on
      static 2D images that do not capture the temporal dynamics and subtleties of
      expression changes. Therefore, there is a need for automated, objective and
      quantitative measurements of facial expressions captured using videos. This paper
      presents a computational framework that creates probabilistic expression profiles
      for video data and can potentially help to automatically quantify emotional
      expression differences between patients with neuropsychiatric disorders and
      healthy controls. Our method automatically detects and tracks facial landmarks in
      videos, and then extracts geometric features to characterize facial expression
      changes. To analyze temporal facial expression changes, we employ probabilistic
      classifiers that analyze facial expressions in individual frames, and then
      propagate the probabilities throughout the video to capture the temporal
      characteristics of facial expressions. The applications of our method to healthy
      controls and case studies of patients with schizophrenia and Asperger's syndrome
      demonstrate the capability of the video-based expression analysis method in
      capturing subtleties of facial expression. Such results can pave the way for a
      video-based method for quantitative analysis of facial expressions in clinical
      research of disorders that cause affective deficits.

PMID- 18045692
TI  - Making quantal analysis more convenient, fast, and accurate: user-friendly
      software QUANTAN.
AB  - Quantal analysis of synaptic transmission is an important tool for understanding
      the mechanisms of synaptic plasticity and synaptic regulation. Although several
      custom-made and commercial algorithms have been created for the analysis of
      spontaneous synaptic activity, software for the analysis of action potential
      evoked release remains very limited. The present paper describes a user-friendly
      software package QUANTAN which has been created to analyze electrical recordings
      of postsynaptic responses. The program package is written using Borland C++ under
      Windows platform. QUANTAN employs and compares several algorithms to extract the
      average quantal content of synaptic responses, including direct quantal counts,
      the analysis of synaptic amplitudes, and the analysis of integrated current
      traces. The integration of several methods in one user-friendly program package
      makes quantal analysis of action potential evoked release more reliable and
      accurate. To evaluate the variability in quantal content, QUANTAN performs
      deconvolution of the distributions of amplitudes or areas of synaptic responses
      employing a ridge regression method. Other capabilities of QUANTAN include the
      analysis of the time-course and stationarity of quantal release. In summary,
      QUANTAN uses digital records of synaptic responses as an input and computes the
      distribution of quantal content and synaptic parameters. QUANTAN is freely
      available to other scholars over the internet.

PMID- 18045695
TI  - Depression like characteristics of 5HTTLPR polymorphism and temperament in
      excessive internet users.
AB  - INTRODUCTION: Excessive internet use (EIU) has been reported to be comorbid with
      depression and the manifestation of its symptoms. This study examines the
      characteristics of excessive internet users that are similar to those of patients
      with depressive disorders in terms of serotonin transporter gene expression and
      harm avoidance. METHODS: 91 male adolescents with EIU and 75 healthy comparison
      subjects were recruited. Between group comparisons were made on genetic
      polymorphisms of the serotonin transport gene and with respect to novelty seeking
      and harm avoidance (HA) of Cloninger's Temperament Character Inventory. RESULTS:
      The homozygous short allelic variant of the serotonin transporter gene (SS
      5HTTLPR) is more frequent in the EIU group (chi(2)=4.38, df=1, p<0.05). The HA
      and Beck Depression Inventory (BDI) scores were significantly higher in the EIU
      group than in the healthy comparison group (t=7.03, df=164, p<0.01; t=2.12,
      df=164, p=0.04). EIU subjects expressing SS-5HTTLPR also showed higher HA (HA1,
      HA2, HA4, and total HA) and Young's internet addiction scale scores than EIU
      subjects expressing the other serotonin transporter gene allele variants (t=2.47,
      df=89, p=0.01; t=2.33, df=89, p=0.02; t=2.17, df=89, p=0.03; t=2.25, df=89,
      p=0.03; t=2.93, df=89, p<0.01 respectively). CONCLUSIONS: The EIU group had
      higher SS-5HTTLPR frequencies, harm avoidance, and BDI scores. SS-5HTTLPR
      expression was closely related to harm avoidance in EIU. The results of this
      study suggest that EIU subjects may have genetic and personality traits similar
      to depressed patients.

PMID- 18045694
TI  - Two-year prospective study of major depressive disorder in HIV-infected men.
AB  - OBJECTIVE: The risks and factors contributing to major depressive episodes in HIV
      infection remain unclear. This 2-year prospective study compared cumulative rates
      and predictors of a major depressive episode in HIV-infected (HIV+) men (N=297)
      and uninfected (HIV-) risk-group controls (N=90). METHODS: By design participants
      at entry were without current major depression, substance dependence or major
      anxiety disorder. Standardized neuromedical, neuropsychological, neuroimaging,
      life events, and psychiatric assessments (Structured Clinical Interview for DSM
      III-R) were conducted semi-annually for those with AIDS, and annually for all
      others. RESULTS: Lifetime prevalence of major depression or other psychiatric
      disorder did not differ at baseline between HIV+ men and controls. On a two-year
      follow-up those with symptomatic HIV disease were significantly more likely to
      experience a major depressive episode than were asymptomatic HIV+ individuals and
      HIV-controls (p<0.05). Episodes were as likely to be first onset as recurrent
      depression. After baseline disease stage and medical variables associated with
      HIV infection were controlled, a lifetime history of major depression, or of
      lifetime psychiatric comorbidity (two or more psychiatric disorders), predicted
      subsequent major depressive episode (p<0.05). Neither HIV disease progression
      during follow-up, nor the baseline presence of neurocognitive impairment,
      clinical brain imaging abnormality, or marked life adversity predicted a later
      major depressive episode. LIMITATIONS: Research cohort of men examined before era
      of widespread use of advanced anti-HIV therapies. CONCLUSIONS: Symptomatic HIV
      disease, but not HIV infection itself, increases intermediate-term risk of major
      depression. Prior psychiatric history most strongly predicted future
      vulnerability.

PMID- 18045696
TI  - Differential alterations in ultrastructural morphology of chicken heterophils and
      lymphocytes induced by corticosterone and lipopolysaccharide.
AB  - Birds are continuously confronted by a large number of stressors, including
      pathogens. Despite their variety, all stressors induce an elevation in plasma
      corticosterone concentration, and consequently increase heterophil to leukocyte
      (H/L) ratio. In order to evaluate and differentiate effects of endocrine (non
      bacterial) and bacterial stress on the proportions and ultrastructural
      characteristics of chicken leukocytes, a series of experiments were conducted
      with seven-week old chickens exposed either to dietary corticosterone or to
      intravenous (i.v.)-injected lipopolysaccharide (LPS). Samples were taken for
      haematological, endocrine, and electron microscopy examination. Administration of
      corticosterone and LPS significantly elevated plasma corticosterone
      concentrations and increased H/L ratios. Electron microscopy observations
      indicated changes in heterophil size, shape, and granulation, and lymphocyte
      cytoplasmic characteristics. Immature heterophils were observed in the peripheral
      blood, suggesting that corticosterone and LPS both stimulate an earlier release
      of heterophils from bone marrow and enhance their influx into blood circulation.
      The LPS induced a degenerative morphology and the destruction of lymphocytes,
      whereas corticosterone appeared to stimulate their redistribution rather than
      destruction. The results indicate that exposure to corticosterone or LPS
      similarly increase H/L ratios, but differentially alter the ultrastructure of
      heterophils and lymphocytes. Elucidation of the mechanisms that cause such
      changes may play an important role in distinguishing between a nonimmune and
      immune stress challenge at the molecular level.

PMID- 18045697
TI  - IgA1 desialylated by microbial neuraminidase forms immune complex with naturally
      occurring anti-T antibody in human serum.
AB  - IgA1 was identified as the most prominent O-glycosylated protein of human serum.
      Desialylation by bacterial (Clostridium perfringens) neuraminidase rendered dot
      blotted IgA1 recognizable by the naturally occurring serum antibody (anti-T)
      directed against Thomsen-Friedenreich antigen, Galbeta1-->3GalNAc-alpha-. On
      Western blot of serum O-glycosylated proteins anti-T recognized nearly all the
      bands including IgA1 as did the T antigen-specific animal lectin galectin-1 but
      only after their desialylation. Agglutination of desialylated human erythrocytes
      by anti-T was effectively inhibited by desialylated IgA1, but not by native IgA1
      or other immunoglobulins. Desialylation of serum by neuraminidase led to
      significantly increased formation of immune complexes containing IgM, the major
      immunoglobulin type in anti-T on one hand and O-glycosylated proteins/IgA1 on the
      other. In further evidence for anti-T-desialylated IgA1 immune complex formation,
      purified anti-T added to desialylated, but not native serum led to formation of
      additional IgA-IgM immune complexes. Also neuraminidase treatment significantly
      reduced the titre of free (non-immune complexed) anti-T in serum, while selective
      removal of anti-T by affinity absorption resulted in considerable decrease in the
      amount of IgA1 that got converted to immune complexes following enzymatic
      desialylation of serum. Formation of immune complex between anti-T and
      neuraminidase-treated IgA1 in serum may be significant since many disease
      pathogens release neuraminidase and since IgA1 is a powerful ligand for tissue
      galectin-1 more so after desialylation. Diabetes also raises serum IgA and
      neuraminidase levels.

PMID- 18045699
TI  - Immunological control of congenital toxoplasmosis in the murine model.
AB  - Toxoplasmosis is a serious disease in humans where it can cause abortion or
      congenital infection if a women is exposed to disease for the first time during
      pregnancy. Infection prior to pregnancy normally results in immunity and which is
      capable of protecting the foetus. Similar observations have been made in the
      BALB/c mouse indicating the potential of mice for studying congenital disease.
      Consequently, the mouse has been used to study how mammals balance the opposing
      needs of maintaining an immunological environment conducive to successful
      pregnancy while attempting to control a dangerous pathogen. Moreover the mouse
      has proven useful for testing the potential of a number of vaccine candidates and
      adjuvants for their ability to prevent congenital infection and/or reduce foetal
      death and abortion.

PMID- 18045698
TI  - Gene delivery GAD 500 autoantigen by AAV serotype 1 prevented diabetes in NOD
      mice: transduction efficiency do not play important roles.
AB  - We previously found that adeno-associated viral vector serotype 2 (AAV-2) muscle
      gene delivery of GAD 500-585 autoantigen efficiently prevented autoimmune
      diabetes in NOD mice. Recent reports suggest that AAV vectors based on serotype 1
      (AAV-1) transduce murine skeletal muscle much more efficiently than AAV-2, with
      reported increases in expression ranging from 2 to 1000-fold. To determine
      whether this increased efficacy of AAV-1 could result in increased therapeutic
      effects in mice, we constructed rAAV1/GAD 500-585 vectors and compared their
      effects in preventing autoimmune diabetes in NOD mice with those of rAAV2/GAD 500
      585 after muscle injection. rAAV(1)/GAD(500-585) gene therapy prevented diabetes
      in NOD mice. However, although much higher level of GAD 500-585 expression was
      found in mice using AAV-1 as gene delivery vector than those using AAV-2, no
      increased efficiency of AAV-1 vectors were found in their capability to prevent
      autoimmune diabetes, as higher titers of rAAV1/GAD 500-585 virus
      (3x10(11)v.g./mouse) were needed to obtain therapeutic effects in NOD mice, a
      titer not different from that of AAV-2. Protection resulted from rAAV1/GAD 500
      585 gene therapy were marked by enhanced Th2 immune response and up-regulated
      CD4+ Foxp3+T regulatory cells, which might actively suppress effector T cells in
      NOD mice. As here we found that the therapeutic effects of AAV1 were not
      positively correlated to it's transduction efficiency, our data suggested that
      the safety and other factors besides efficiency should be considered when use
      different AAV serotype to treat autoimmune disease.

PMID- 18045700
TI  - No association between hearing loss due to bilateral otitis media with effusion
      and Denver-II test results in preschool children.
AB  - OBJECTIVE: Otitis media with effusion (OME) is the most common cause of acquired
      hearing loss in childhood and has been associated with delayed language
      development and behavioral problems. In this study, children with an evidently
      recurrent otitis media were investigated. The present study examines the
      association between hearing loss versus developmental screening test parameters
      of preschool children. METHODS: Sixteen children with bilateral otitis media were
      compared with age-matched same number of children with normal hearing (controls).
      RESULTS: Language and verbal cognitive abilities were not affected significantly
      as a result of the presence of hearing loss because of OME. Using internationally
      standardized Denver-II test to evaluate the language development and other
      developmental screening parameters, no significant difference was found between
      the patient and control groups. CONCLUSIONS: This study failed to find any
      association between the hearing loss due to otitis media with effusion and speech
      and language parameters in preschool children.

PMID- 18045701
TI  - Factors affecting the persistence of tympanic membrane perforation developed with
      the extubation of ventilation tube.
AB  - OBJECTIVE: To determine which factors are associated with persistence of the
      tympanic membrane (TM) perforation detected after a spontaneous extrusion or
      surgical removal of a ventilation tube (VT). METHODS: We conducted a
      retrospective chart review of all patients who underwent ventilation tube
      insertion from 1995 to 2003 at our institution. We identified 909 ears in which
      we could see the final state of TM and found 89 ears that fitted the
      inclusion/exclusion criteria. Various factors were analyzed to determine the
      factors associated with persistence of a TM perforation after VT extrusion or
      removal in 89 ears, including age at the time of tube extrusion or removal, sex,
      extubation pattern, intubation period, reason for VT insertion, history of
      previous VT insertions, condition of the TM when a perforation was detected, and
      previous adenoidectomy. RESULTS: Three factors were found to be statistically
      significant predictors of permanent perforation including age, extubation pattern
      and intubation period on univariate analysis. However, on multivariate analysis,
      extubation pattern, intubation period remained as statistically significant
      predictors. CONCLUSIONS: Our data shows that factors affecting the permanent TM
      perforation after the spontaneous extrusion or surgical removal of VT include
      extubation pattern and intubation period.

PMID- 18045702
TI  - Evaluation of a novel real-time PCR system for cytomegalovirus DNA quantitation
      on whole blood and correlation with pp65-antigen test in guiding pre-emptive
      antiviral treatment.
AB  - Successful pre-emptive anti-cytomegalovirus (CMV) therapy relies on sensitive,
      specific and reproducible tests for CMV detection. Real-time polymerase chain
      reaction (PCR) for CMV-DNA provides a superior reproducibility and sensitivity
      than pp65-antigenemia. Evaluation of a novel commercial real-time PCR for CMV-DNA
      associated with a fully automated DNA extraction from whole blood (WB) was
      performed, studying the correlation with pp65-antigenemia in guiding pre-emptive
      therapy. Analytical evaluation showed that PCR correctly quantitated CMV from 500
      to 500,000copies/ml with a close correlation with expected values (r=0.999).
      Clinical evaluation on 375 consecutive WB samples from 48 infected patients (18
      pre-emptively treated for pp65 values >/=50 positive cells) showed that according
      to pp65-antigenemia of 0, 1-10, 11-49 and >/=50 positive cells, median DNA levels
      were 3.7, 3.9, 4.6 and 5.6 log(10)copies/ml, respectively. According to existing
      pre-emptive treatment criteria based on pp65-antigenemia, receiver-operating
      curve analysis indicated 5.3log/ml (200,000genomes/ml) as the best CMV-DNA level
      to discriminate between patients requiring pre-emptive therapy and those who did
      not (positive predictive value: 91%; negative predictive value: 74%; sensitivity
      and specificity: 68 and 93%). In conclusion, real-time PCR provides reliable
      results for monitoring the developing of CMV infection, allowing for the
      definition of CMV-DNA thresholds associated with infection progress.

PMID- 18045703
TI  - The role of cyp1a and heme oxygenase 1 gene expression for the toxicity of 3,4
      dichloroaniline in zebrafish (Danio rerio) embryos.
AB  - Expression profiling of exposed cells or organisms can reveal genes sensitive to
      environmental contaminants or toxic compounds. However, the mechanistic relevance
      of altered gene expression often remains to be elucidated. Toxicant-dependent
      differential gene expression may indicate protection to or mediation of toxicity.
      Previous studies revealed a number of differentially transcribed genes in
      zebrafish embryos exposed to the model compound 3,4-dichloroaniline (3,4-DCA). To
      evaluate the significance of two of the most sensitive genes, cytochrome P 450 1a
      (cyp1a) and heme oxygenase 1 (hmox1), for 3,4-DCA toxicity, RNA interference
      mediated knockdown and overexpression studies have been conducted. Knockdown of
      gene transcription by siRNA for cyp1a and hmox1 enhanced the frequency of
      developmental disorders in embryos exposed to 3,4-DCA. Vice versa, injection of
      cyp1a and hmox1 mRNA reduced the number of disorders. The opposite effects of
      siRNA and mRNA injection clearly indicate a protective role of the corresponding
      proteins. Functional studies such as the one presented could be applied to a wide
      variety of genes. They would be ideally suited to study the role of genes
      identified from toxicogenomic studies in the zebrafish embryo model.

PMID- 18045704
TI  - Accumulation and elimination kinetics of dietary endosulfan in Atlantic salmon
      (Salmo salar).
AB  - The carry-over of dietary endosulfan to the fillet of farmed Atlantic salmon was
      studied. The uptake and elimination rate constants of the alpha and beta isoform
      of endosulfan were determined in seawater adapted Atlantic salmon (initial weigh
      173+/-25 g) fed on endosulfan enriched diets (724 and 315 microg kg(-1) for alpha
      and beta-endosulfan, respectively) for 92 days, followed by a 56 days depuration
      period with feeding on control diets (<0.3 microg kg(-1) endosulfan). The
      accumulation of the toxic metabolite endosulfan sulphate, which was not detected
      (<0.5 microg kg(-1)) in the experimental feeds, was also determined. Dietary beta
      endosulfan was more persistent than alpha-endosulfan as demonstrated by a higher
      uptake (41+/-8% vs. 21+/-2%) and lower elimination (26+/-2 x 10(-3) day(-1) vs.
      40+/-1 x 10(-3) day(-1)) rate constants, and a higher biomagnification factor
      (0.10+/-0.026 vs. 0.05+/-0.003, p<0.05). Based on the decrease in diastereometric
      factor over time, biotransformation was estimated to account for at least 50% of
      the endosulfan elimination. The formation of the metabolite endosulfan sulphate
      comprised a maximum 1.2% of the total accumulation of endosulfan. Using a simple
      one-compartmental model and the experimentally-determined rate constants, it was
      predicted that only dietary concentration higher than 7.5 mg kg(-1) would cause
      the estimated maximum residue level (MRL) in fillet of 0.47 mg kg(-1) to be
      exceeded. Model estimations also predict that current EU maximum permitted levels
      in fish feeds (0.005 mg kg(-1)) would give fillet concentrations that are under
      the detection limit (0.3 microg kg(-1)), which is in agreement with the general
      absence of endosulfan in monitored farmed Atlantic salmon.

PMID- 18045705
TI  - Severe mitral regurgitation in Tako-Tsubo cardiomyopathy.
AB  - Severe emotional or physical stress precedes Tako-Tsubo cardiomyopathy (TTC)
      which is characterized by transient left ventricular impairment in absence of
      coronary artery disease. In this case we report from a female patient presenting
      with characteristic features of TTC after examination of upper gastrointestinal.
      Additionally, severe mitral regurgitation due to acute rupture of the
      posteromedial papillary muscle was present. Normal left ventricular function was
      documented before surgical valve repair was performed. TTC is reported to be
      associated with several complications. This is the first report of TTC
      accompanied by severe mitral valve regurgitation due to rupture of a papillary
      muscle.

PMID- 18045706
TI  - Cardiac abnormalities in McLeod syndrome.
AB  - We report the cardiac features of seven patients with X-linked McLeod
      neuroacanthocytosis syndrome, a multi-system disorder resembling Huntington's
      disease and cardiac manifestations in about half of the patients reported to
      date. One patient presented with a cardiomyopathy (normal size of the left
      ventricle with concentric remodeling and mildly impaired ejection fraction, 43%).
      This patient died from sudden cardiac death in the absence of any cardiovascular
      risk factors. Autopsy demonstrated eccentric hypertrophy and mild left
      ventricular dilatation. Histopathology was not specific and revealed focal
      myocyte hypertrophy, slight variation of myofiber size and patchy interstitial
      fibrosis.

PMID- 18045707
TI  - Use of PTFE-covered stent in acute myocardial infarction of aneurysmatic coronary
      artery.
AB  - Coronary artery aneurysms are reported between 0.1-4.9% in coronary
      angiographies. Vessel wall weakening, inflammation and endothelial damage play a
      role in their development. They may compromise the coronary flow and play a
      source for recurrent embolization of thrombus fragments. Here we report a patient
      with coronary artery aneurysm in left anterior descending artery with a critical
      thrombosed proximal segment and resulting in acute myocardial infarction.
      Coronary artery aneurysm is managed with polytetrafluoroethylene (PTFE) covered
      stent and proximal infarct related segment is treated with a bare metal stent.
      Coronary patency is provided without any obvious complication at the end of the
      procedure.

PMID- 18045708
TI  - Echocardiography in conscious 1K,1C Goldblatt rabbits reveals typical features of
      human hypertensive ventricular diastolic dysfunction.
AB  - Diastolic dysfunction is a major component of hypertensive cardiomyopathy
      contributing to a progressive evolution towards overt heart failure. To establish
      an experimental model that could mimic the human clinical pattern, we
      standardized the surgery in one-kidney, one-clip Goldblatt (1K,1C) rabbits and
      characterized their hypertensive cardiopathy by echocardiography. Five weeks
      after placement of a stenotic string around the left renal artery and removal of
      the right kidney, arterial pressure was measured and an echocardiography
      performed in conscious animals. An hypertrophic cardiopathy associated with
      hypertension and a primary trouble of the LV relaxation was observed. This
      trouble was characterized by a reversion of E/A and Ea/Aa ratios and an increase
      of the isovolumic relaxation time and Tau index, without augmentation of left
      ventricular filling pressures. We show for the first time, in this experimental
      model, a diastolic dysfunction pattern close to the human one. Moreover,
      echocardiography in a conscious state gives the opportunity to use this model for
      future chronic pharmacological studies.

PMID- 18045709
TI  - Prognostic value of pentraxin 3 in patients with chronic heart failure.
AB  - BACKGROUND: A long pentraxin, PTX3, is produced by vascular cells or inflammatory
      cells and released into the circulation, possibly reflecting local inflammation
      in the cardiovascular system. AIM: This study was designed to assess the clinical
      significance of plasma pentraxin 3 (PTX3) levels in chronic heart failure (CHF).
      METHODS: We measured plasma PTX3 levels in 37 patients with non-ischemic CHF
      (dilated cardiomyopathy) using enzyme-linked immunosorbent assay (ELISA) methods.
      RESULTS: The plasma PTX3 levels were higher in CHF patients than in healthy
      subjects (P=0.001), and the CHF patients in the highest tertile of plasma PTX3
      levels had more cardiac events than the patients in the lowest tertile (42% vs.
      0%, P=0.02). Multivariate regression analysis showed that PTX3 was the most
      significant predictor of cardiac events (hazard ratio 1.912 for each increase in
      PTX3 of 1 ng/ml, P=0.019, 95% CI 1.114-3.282). In addition, PTX3 was strikingly
      expressed in human myocardial cells obtained from a biopsy specimen in a patient.
      CONCLUSION: Plasma PTX3 levels might be a potentially useful biomarker to predict
      prognosis as well as to detect inflammatory status in patients with CHF.

PMID- 18045710
TI  - Pseudoaneurysm of the left ventricle with moderate left-to-right shunt.
AB  - A 79 year old man was admitted to the hospital with increased breathlessness and
      fatigue on minimal exertion, and this since a few weeks. Transthoracic and
      transesophageal echocardiography, followed by cardiovascular magnetic resonance
      imaging, demonstrated a cardiac pseudoaneurysm connected with both ventricular
      cavities resulting in an extracardiac left-to-right shunt, with even re
      perforating into the right atrium. These findings were suggested to be sequels
      from an inferior myocardial infarction. Given the age and the complex
      characteristics of the aneurysm, conservative management was the treatment of
      choice. At one year follow-up the patient was still doing well.

PMID- 18045711
TI  - Anuric acute renal failure and pulmonary oedema: a case for urgent action.
AB  - Atherosclerotic renovascular disease (ARVD) is a common manifestation of
      atheromatous disease. Whilst it usually displays a chronic and asymptomatic
      course, it is increasingly recognised as playing a significant pathophysiological
      role in a number of clinical presentations. Anuric acute renal failure (ARF), due
      to thrombotic renal artery occlusion (RAO) or progression to critical narrowing,
      however, is a rare complication of this. We report a patient who presented with
      anuric ARF and pulmonary oedema secondary to bilateral renal artery disease (one
      chronic RAO, one highly critical renal artery stenosis (RAS)). She showed a good
      response to renal revascularisation with restoration of renal function, even when
      this was performed after six days of anuria.

PMID- 18045712
TI  - Acute effect of oral flavonoid-rich dark chocolate intake on coronary
      circulation, as compared with non-flavonoid white chocolate, by transthoracic
      Doppler echocardiography in healthy adults.
AB  - PURPOSE: To assess the effects of the oral intake of flavonoid-rich dark
      chocolate on coronary circulation, we measured coronary flow velocity reserve
      (CFVR) by noninvasive transthoracic Doppler echocardiography (TTDE) in healthy
      adult subjects. MATERIALS AND METHODS: The study was a randomized, single-blind
      design conducted for 2 weeks in 39 healthy men (mean age 29.7+/-3.9 years, range
      23-40 years). Subjects were randomly assigned a daily intake of either flavonoid
      rich dark chocolate (Meiji Black Chocolate 45 g, Meiji Seika kaisya Ltd,
      including cacao polyphenol 550 mg/day, 200 kcal) or non-flavonoid white chocolate
      (Meiji White Chocolate 35 g, Meiji Seika kaisya Ltd, including cacao polyphenol 0
      mg/day, 140 kcal) as a control. CFVR was recorded by TTDE, and assessed before
      and after 2 weeks of intake. At the same time, we also assessed serum asymmetric
      dimethylarginine, 8-isoprostanes, and malondialdehyde-modified low-density
      lipoprotein (MDA-LDL) as markers of oxidative stress. RESULTS: Flavonoid-rich
      dark chocolate consumption significantly improved CFVR (3.38+/-0.49 before
      intake, 4.28+/-0.85 after intake; p<0.01), whereas non-flavonoid white chocolate
      consumption did not (3.28+/-0.49 before intake, 3.16+/-0.49 after intake;
      p=0.44). All predictor variables were used as dependent variables in a multiple
      regression model of the incremental change in CFVR after 2 weeks of chocolate
      intake. Intake of dark (but not white) chocolate, MDA-LDL, triglyceride (TG) and
      heart rate (HR) significantly influenced the change of CFVR after 2 weeks of
      intake (p<0.01) according to the multiple regression formula: Y=1.01X(1)
      0.005X(2)-0.003X(3)-0.017X4 (Y=change in CFVR after 2 weeks of chocolate intake,
      X1=intake of dark (but not white) chocolate, X2=MDA-LDL, X3=TG, X4=HR).
      CONCLUSION: Flavonoid-rich dark chocolate intake significantly improved coronary
      circulation in healthy adults, independent of changes in oxidative stress
      parameters, blood pressure and lipid profile, whereas non-flavonoid white
      chocolate had no such effects.

PMID- 18045713
TI  - Latent left ventricular outflow tract obstruction induced by abnormal
      hypertrophic papillary muscle caused myocardial ischemia.
AB  - Left ventricular outflow tract (LVOT) obstruction is a typical recognized feature
      in hypertrophic cardiomyopathy. However, it has been shown in other clinical
      scenarios such as acute ischemia. In some patients, LVOT obstruction may only be
      detectable with provocation testing such as exercise stress. Accurate and timely
      diagnosis, therefore, relies on recognizing an echocardiographic substrate in
      which LVOT obstruction may occur, such as ventricular hypertrophy. This report
      describes the case of a patient presenting with effort ECG and signs of
      myocardial ischemia, with no significant narrowing of coronary arteries but with
      latent LVOT obstruction due to the presence of an abnormal hypertrophic papillary
      muscle instead of a typical ventricle hypertrophy.

PMID- 18045714
TI  - Vaccination of free-living juvenile wild rabbits (Oryctolagus cuniculus) against
      myxomatosis improved their survival.
AB  - For several decades, the populations of the European wild rabbit (Oryctolagus
      cuniculus) have declined, which is partly due to myxomatosis. Vaccination against
      this disease is expected to contribute to restoration of rabbit populations but
      the actual impact of myxomatosis is not well known and vaccination might have
      some negative effects. We analyzed the capture-mark-recapture data obtained in a
      4-year field experiment (1991-1994) in a park near Paris, France wherein 300 out
      of 565 seronegative juvenile rabbits were vaccinated at first capture against
      myxomatosis with the nontransmissible Dervaximyxo SG33 vaccine. After accounting
      for weight at first capture, age-class (juvenile/adult), "trap-happiness" and
      season (spring/autumn) of the capture event, vaccinated rabbits had 1.8-fold
      greater odds of surviving than the unvaccinated rabbits. The average summer
      survival risk for vaccinated juveniles was 0.63 (+/-0.08 S.E.) whereas it was
      0.48 (+/-0.08 S.E.) for unvaccinated juvenile rabbits.

PMID- 18045715
TI  - Long-term stability of electroencephalographic asymmetry and power in 3 to 9 year
      old children.
AB  - We investigated the test-retest stability of resting EEG asymmetry and power in
      the alpha frequency range across a 0.6- to 3-year interval in 125 children (57
      girls and 68 boys) for two age groups, 87 preschool children (3 to 5 year-olds)
      and 38 school-age children (6 to 9 year-olds). Children were from families with a
      parent's history of unipolar or bipolar depression (36 girls and 43 boys) or
      control families with no parent history of depression nor any other psychiatric
      disorder (21 girls and 25 boys). Frontal EEG asymmetry stability was low to
      moderate; intraclass correlations ranged from zero to 0.48 in the eyes-open
      condition, and from 0.19 to 0.45 in the eyes-closed condition. Also, parietal EEG
      asymmetry was low to moderate; intraclass correlations ranged from 0.21 to 0.52
      in the eyes-open condition and from 0.27 to 0.72 in the eyes-closed condition.
      Stability of EEG asymmetry was not related to age, sex of the child, or parent's
      history of mood disorder. Frontal and parietal EEG power appeared moderately to
      highly stable. Intraclass correlations were between 0.65 and 0.86 in the eyes
      open condition and between 0.52 and 0.90 in the eyes-closed condition. Although
      stability of EEG power was not statistical significantly different between
      preschool and school-age children, it consistently showed higher stability values
      in school-age children than in preschool children. Stability in school-age
      children approached values as has been reported for adults. The findings provide
      partial support to the concept of frontal EEG asymmetry as a trait marker in
      childhood.

PMID- 18045716
TI  - Involvement of calcineurin in glutamate-induced mitochondrial dynamics in
      neurons.
AB  - Alterations in the morphology and movement of mitochondria influence neuronal
      viability. However, the precise mechanisms of such alterations are unclear. In
      this study, we showed calcineurin was involved in the regulation of mitochondrial
      dynamics. Glutamate stimulation inhibited mitochondrial movement and decreased
      mitochondrial length in neurons. FK506 and cyclosporine A, calcineurin
      inhibitors, attenuated the effects of glutamate on mitochondrial dynamics. It was
      also found that glutamate treatment dephosphorylated, a proapoptotic protein, Bad
      and promoted its translocation to mitochondria in neurons via calcineurin. These
      results provide important new insights into intracellular signaling pathways that
      regulate mitochondrial dynamics and neuronal cell death.

PMID- 18045717
TI  - Serotonin2C receptor mRNA editing in neuropathic pain model.
AB  - We investigated the effects on 5HT(serotonin) 2C receptor RNA editing efficiency
      of contusive SCI (spinal cord injury). Using cloning followed by sequence
      analysis on spinal cord samples taken, we compared mRNA editing. Our results
      might be evidence of a functional adaptation mechanism in which increased
      expression of 5HT2C mRNA isoforms that encode receptors more sensitive to
      serotonin works to activate brainstem-spinal descending 5HT systems to, in
      effect, suppress transmission of nociceptive signals from primary afferent
      neurons to the spinal dorsal horn.

PMID- 18045718
TI  - Virulence characterization and genotypic analyses of Listeria monocytogenes
      isolates from food and processing environments in eastern China.
AB  - In this study, twenty L. monocytogenes food-related isolates collected from
      eastern China Zhejiang province were compared by in vivo LD50 assays as well as
      in vitro cytopathic plaque forming assay. Nineteen L. monocytogenes isolates
      (19/20) were as virulent as reference strain 10403S, while the isolate M4 had low
      pathogenicity. The unique isolate M4 fell into lineage III based on the partial
      nucleotide variations of actA, while the other isolates belonged to the more
      common lineages I and II. L. monocytogenes isolates were grouped in 17 to 19
      subtypes using pulsed-field gel electrophoresis (PFGE) with SmaI digestion, and
      multilocus sequence typing (MLST) based on three virulence genes (actA, inlA and
      inlB) and four housekeeping genes (betL, dat, recA and sigB). The virulence genes
      based MLST had better discriminatory power than that targeting the housekeeping
      genes (0.990 vs 0.895), similar to PFGE (0.976). An isolate from the processing
      desk was found having the same pulsotype as the two isolates from final shrimp
      products in the same plant, indicating that process contamination could be the
      source of Listeria contamination.

PMID- 18045719
TI  - Highly protective E2-CSFV vaccine candidate produced in the mammary gland of
      adenoviral transduced goats.
AB  - Classical swine fever virus is the etiological agent of the most economically
      important highly contagious disease of swine worldwide. E2 is the major envelope
      glycoprotein present as a homodimer on the outer surface of the virus and
      represents an important target for the induction of neutralizing immune response
      against the viral infection. The E2 extracellular domain was expressed in the
      milk of adenoviral transduced goats at the highest level about 1.2g/L. The
      recombinant glycoprotein was purified from clarified serum milk by a single metal
      chelate affinity chromatography step, as a homodimer of approximately 100kDa and
      purity over 98%. Glycosylation analysis showed the presence of oligomannoside,
      hybrid and complex type N-glycans, attached to the recombinant E2. The capacity
      of goat milk-derived E2 antigen to protect pigs from both classical swine fever
      clinical signs and viral infection was assessed in a vaccination and challenge
      trial. The immunized pigs became protected after challenge with 10(5) LD(50) of a
      highly pathogenic CSFV strain. In the context of veterinary vaccines, this
      expression system has the advantages that the recombinant antigen could be
      harvested in about 48h after adenoviral transduction with expression levels in
      the range of g/L. This approach may turn into a scalable expression system for
      the assessment and production of veterinary vaccines.

PMID- 18045720
TI  - Sphingomyelin induces structural alteration in canine parvovirus capsid.
AB  - One of the essential steps in canine parvovirus (CPV) infection, the release from
      endosomal vesicles, is dominated by interactions between the virus capsid and the
      endosomal membranes. In this study, the effect of sphingomyelin and phosphatidyl
      serine on canine parvovirus capsid and on the phospholipase A(2) (PLA(2))
      activity of CPV VP1 unique N-terminus was analyzed. Accordingly, a significant
      (P< or =0.05) shift of tryptophan fluorescence emission peak was detected at pH
      5.5 in the presence of sphingomyelin, whereas at pH 7.4 a similar but minor shift
      was observed. This effect may relate to the exposure of VP1 N-terminus in acidic
      pH as well as to interactions between sphingomyelin and CPV. When the phenomenon
      was further characterized using circular dichroism spectroscopy, differences in
      CPV capsid CD spectra with and without sphingomyelin and phosphatidyl serine were
      detected, corresponding to data obtained with tryptophan fluorescence. However,
      when the enzymatic activity of CPV PLA(2) was tested in the presence of
      sphingomyelin, no significant effect in the function of the enzyme was detected.
      Thus, the structural changes observed with spectroscopic techniques appear not to
      manipulate the activity of CPV PLA(2), and may therefore implicate alternative
      interactions between CPV capsid and sphingomyelin.

PMID- 18045721
TI  - SARS coronavirus accessory proteins.
AB  - The emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV) has
      led to a renewed interest in studying the role of accessory proteins in
      regulating coronavirus infections in the natural host. A significant body of
      evidence has accumulated in the area of SARS-CoV and host interactions that
      indicate that the accessory proteins might play an important role in modulating
      the host response to virus infection and thereby, contribute to pathogenesis. In
      this review, we have compiled the current knowledge about SARS-CoV accessory
      proteins, obtained from studies in cell culture systems, reverse genetics and
      animal models, to shed some light into the possible role of these proteins in the
      propagation and virulence of SARS-CoV in its natural host. We conclude by
      providing some questions for future studies that will greatly advance our
      knowledge about the biological significance and contributions of the accessory
      proteins in the development of SARS in humans.

PMID- 18045722
TI  - Mannosylated semiconductor quantum dots for the labeling of macrophages.
AB  - Quantum dots show strong fluorescence emission and long stability compared with
      classical organic fluorescent dyes; therefore, quantum dots take the place of
      other dyes in Western blot, immunostaining and bioimaging. Since macrophage plays
      crucial roles in many pathophysiological processes, tracking macrophage
      migration, homing and fate is important for understanding the complex roles of
      macrophages in disease or developing disease diagnosis. Because of the high
      expression of mannose receptor on macrophage, mannosylation is an attractive
      strategy to label macrophage. In this study, using polyethylene-glycol (PEG)
      (M.W. 2,000; PEG(2,000))-coated quantum dots, we prepared mannosylated PEG(2,000)
      (Man-PEG(2,000)) quantum dots for labeling macrophage. The uptake characteristics
      of Man-PEG(2,000) quantum dots were investigated by primary cultured peritoneal
      macrophages. The uptake of Man-PEG(2,000) quantum dots was inhibited by an excess
      amount of mannose, suggesting mannose receptor-mediated uptake of Man-PEG(2,000)
      quantum dots. The result of MTT assay suggested the extremely low cytotoxicity of
      Man-PEG(2,000) quantum dots. In conclusion, the Man-PEG(2,000) synthesized is
      safe and is taken up by macrophage mannose receptor recognition.

PMID- 18045723
TI  - Prevalence of the impaired glucose metabolism and its association with risk
      factors for coronary artery disease in women with gestational diabetes.
AB  - Gestational diabetes (GDM) has increased risk of diabetes (DM2), a coronary
      artery disease (CAD) equivalent. The aim of this study was to determine the
      prevalence of impaired glucose metabolism (IGM) in GDM and its association with
      risk factors for CAD. A cohort of 109 women with GDM underwent a glucose
      tolerance test which classified them into three groups: diabetic (DM2) (fasting
      glucose (G) >or=126mg/dl or plasma glucose 2h (2-h G) >or=200mg/dl); impaired
      glucose tolerance (IGT) (G 100-125mg/dl and/or 2-h G 140-199mg/dl); and normal
      (N) (G<100mg/dl and/or 2-h<140mg/dl). They were compared for pre-gestational
      (PBMI) and current (CBMI) body mass index, systolic (SBP) and diastolic blood
      pressure (DBP), G, lipids, fibrinogen and C-reactive protein (hsCRP). Thirty two
      months after delivery, 17.4% presented DM2, 39.4% IGT and 43.1% were N. PBMI,
      CBMI, SBP and DBP were significantly higher in the DM2 than N. G was higher in
      DM2 and IGT. HDL-cholesterol (HDL-C) was higher in the N (p=0.02) and the
      triglycerides (TG) were higher in DM2 (p=0.02). The groups showed significantly
      different levels of hsCRP (p=0.002). We conclude that the high prevalence of IGM,
      overweight/obesity, dyslipidemia and altered inflammatory markers, make GDM a
      high-risk situation for CAD.

PMID- 18045725
TI  - Light transport in tissue by 3D Monte Carlo: influence of boundary voxelization.
AB  - Monte Carlo (MC) based simulations of photon transport in living tissues have
      become the "gold standard" technique in biomedical optics. Three-dimensional (3D)
      voxel-based images are the natural way to represent human (and animal) tissues.
      It is generally believed that the combination of 3D images and MC based
      algorithms allows one to produce the most realistic models of photon propagation.
      In the present work, it is shown that this approach may lead to large errors in
      the MC data due to the "roughness" of the geometrical boundaries generated by the
      presence of the voxels. In particular, the computed intensity of the light
      detected on the tissue surface of a simple cubic tissue phantom may display
      errors from -80% to 120%. It is also shown that these errors depend in a complex
      manner on optical and geometrical parameters such as the interoptode distance,
      scattering coefficient, refractive index, etc. and on the degree of voxelization
      ("roughness") of the boundaries. It is concluded that if one wants to perform
      reliable 3D Monte Carlo simulations on complex geometries, such as human brain,
      skin or trabecular bone, it is necessary to introduce boundary meshing techniques
      or other equivalent procedures in the MC code to eliminate the deleterious effect
      of voxelization.

PMID- 18045724
TI  - Cost of preventing variceal rebleeding with transjugular intrahepatic portal
      systemic shunt and distal splenorenal shunt.
AB  - BACKGROUND/AIMS: We examined the cost and cost effectiveness of distal
      splenorenal shunt (DSRS) and transjugular intrahepatic portosystemic shunt (TIPS)
      in the prevention of variceal rebleeding. METHODS: Patients participated in a
      randomized controlled trial comparing DSRS to TIPS. Quality of life (QOL) was
      measured using SF-36 preceding randomization and yearly thereafter. Cost utility
      analysis was performed using TreeAge DATA. Costs for both in- and out-patient
      events and interventions were obtained for each patient. Costs using coated
      stents were estimated using different rates of stenosis. Incremental cost
      effectiveness ratios (ICERs) were determined at 1, 3 and 5 years. RESULTS: The
      average yearly costs of managing patients after TIPS and DSRS over 5 years were
      similar, $16,363 and $13,492, respectively. Cost of TIPS for surviving patients
      exceeded the cost of DSRS at years 3 and 5 but not significantly. ICERs per life
      saved favored TIPS at year 5 ($61,000). If coated rather than bare stents were
      used the cost effectiveness of TIPS increased slightly. CONCLUSIONS: TIPS is as
      effective as DSRS in preventing variceal rebleeding and may be more cost
      effective. TIPS, in all aspects, is equal to DSRS in the prevention of variceal
      rebleeding in patients who are medical failures.

PMID- 18045726
TI  - Predicting cell-penetrating peptides.
AB  - Possibility to predict short peptide sequences capable to penetrate the plasma
      membrane opens new opportunities for developing peptide based intracellular
      delivery vectors, called cell-penetrating peptides (CPPs). Predictions of CPPs,
      however are often based on trial and error and may not always lead to new potent
      sequences. In this review we discuss different problems associated with CPP
      prediction. Additionally, the used methods of CPP prediction are compared. Also,
      a few suggestions are made for designing new CPP sequences and improvement of
      predictions.

PMID- 18045727
TI  - Methodological and cellular aspects that govern the internalization mechanisms of
      arginine-rich cell-penetrating peptides.
AB  - Peptides including HIV-1 Tat peptide and oligoarginines represent arginine-rich
      membrane-permeable vectors that attain efficient intracellular delivery of
      bioactive molecules. The importance of the arginine residues or their guanidino
      functions is now appreciated for efficient internalization of the Tat peptide,
      and based on this, various novel arginine/guanidino-rich vectors have now been
      developed. However, molecular detail of their method(s) of internalization are
      still debated. This review summarizes our current understandings of endocytic and
      non-endocytic aspects of internalization of arginine-rich peptide vectors. We
      highlight the possibility of simultaneous employment of multiple internalization
      pathways, the contribution of which is dependent on a number of factors.
      Similarities and dissimilarities among the internalization methods of typical
      peptide vectors and other guanidino-rich vectors including branched-chain, beta
      peptide, and sugar-based vectors, are also discussed.

PMID- 18045728
TI  - Approaches for the development of solid and semi-solid lipid-based formulations.
AB  - Interest in Lipid Based Drug Delivery (LBDD) has developed over the past decade
      fuelled by a better understanding of the multiple roles lipids may play in
      enhancing oral bioavailability. Moreover, the emergence of novel excipients with
      acceptable regulatory and safety profiles coupled with advances in formulation
      technologies have greatly improved the potential for successful lipid based
      formulations. With the growing interest in this field, there is an increasing
      need for guidelines in excipient selection and characterization; material
      handling, formulation design, and processing techniques to obtain effective and
      patient-compliant dosage forms. The aim of this review is to present the recent
      approaches in selecting the most appropriate lipid system(s); methods for
      characterization of their behavior in vitro and in vivo; and the current
      formulation and processing techniques to obtain various solid dosage forms.

PMID- 18045730
TI  - Thermodynamic studies and binding mechanisms of cell-penetrating peptides with
      lipids and glycosaminoglycans.
AB  - Cell-penetrating peptides (CPPs) traverse the membrane of biological cells at low
      micromolar concentrations and are able to take various cargo molecules along
      with. Despite large differences in their chemical structure, CPPs share the
      structural similarity of a high cationic charge density. This property confers to
      them the ability to bind electrostatically membrane constituents such as anionic
      lipids and glycosaminoglycans (GAGs). Controversies exist, however, about the
      biological response after the interaction of CPPs with such membrane
      constituents. Present review compares thermodynamic binding studies with
      conditions of the biological CPP uptake. It becomes evident that CPPs enter
      biological cells by different and probably competing mechanisms. For example,
      some amphipathic CPPs traverse pure lipid model membranes at low micromolar
      concentrations--at least in the absence of cargos. In contrast, no direct
      translocation at these conditions is observed for non-amphipathic CPPs. Finally,
      CPPs bind GAGs at low micromolar concentrations with potential consequences for
      endocytotic pathways.

PMID- 18045729
TI  - Biomimetic materials for tissue engineering.
AB  - Tissue engineering and regenerative medicine is an exciting research area that
      aims at regenerative alternatives to harvested tissues for transplantation.
      Biomaterials play a pivotal role as scaffolds to provide three-dimensional
      templates and synthetic extracellular matrix environments for tissue
      regeneration. It is often beneficial for the scaffolds to mimic certain
      advantageous characteristics of the natural extracellular matrix, or
      developmental or wound healing programs. This article reviews current biomimetic
      materials approaches in tissue engineering. These include synthesis to achieve
      certain compositions or properties similar to those of the extracellular matrix,
      novel processing technologies to achieve structural features mimicking the
      extracellular matrix on various levels, approaches to emulate cell-extracellular
      matrix interactions, and biologic delivery strategies to recapitulate a signaling
      cascade or developmental/wound healing program. The article also provides
      examples of enhanced cellular/tissue functions and regenerative outcomes,
      demonstrating the excitement and significance of the biomimetic materials for
      tissue engineering and regeneration.

PMID- 18045732
TI  - Stereotactic, high single-dose irradiation of stage I non-small cell lung cancer
      (NSCLC) using four-dimensional CT scans for treatment planning.
AB  - We reviewed response rates, local control, survival and side effects after non
      fractionated stereotactic high single-dose body radiation therapy for lung
      tumors. Forty patients with stage I non-small cell lung cancer (NSCLC) underwent
      radiosurgery involving single-dose irradiation. The standard dose prescribed to
      the isocenter was 30Gy with an axial safety margin of 10mm and a longitudinal
      safety margin of 15mm. The planning target volume (PTV) was defined using three
      CT scans with reference to the phases of respiration so that the movement span of
      the clinical target volume (CTV) was enclosed. The volume of the bronchial
      carcinomas varied from 4.2 to 130cm(3) (median: 19.5cm(3)), and the PTV derived
      from four-dimensional CT (4D-CT) scans using image fusion ranged from 15.6 to
      390.5cm(3) (median: 101cm(3)). Tumor size ranged from 1.7 to 10cm at largest
      focuses. Follow-up periods varied from 6.0 to 61.5 months (median: 20 months). We
      observed three local tumor recurrences, resulting in an actuarial local tumor
      control of 81% at 3 years. With the exception of two rib fractures, no serious
      late toxicity was observed. The overall survival probability rates were: 2 years:
      66%, 3 years: 53% (median overall survival: 37 months). Cancer-specific survival
      probability was: 2 years: 71%, 3 years: 57%. Non-fractionated high single-dose
      SBRT for NSCLC is more convenient for the patient and less time-consuming than
      hypofractionated SBRT, but data dealing with this method are still scanty. This
      alternative treatment results in favourable local control and acceptable
      toxicity.

PMID- 18045731
TI  - Phase III randomized, double-blind study of maintenance CAI or placebo in
      patients with advanced non-small cell lung cancer (NSCLC) after completion of
      initial therapy (NCCTG 97-24-51).
AB  - PURPOSE: This study assessed whether maintenance therapy with
      carboxyaminoimidazole (CAI), compared to placebo, prolonged overall survival in
      stage IIIB/IV NSCLC patients who had tumour regression or stable disease after
      treatment with one chemotherapy regimen. METHODS: After completion of
      chemotherapy, patients were randomized to receive daily oral CAI at 250mg or
      placebo. Treatment continued until patient refusal, disease progression or
      unacceptable adverse event (AE). Quality of life (QOL) was assessed by UNISCALE
      and Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L). RESULTS:
      Registration was halted early for slow accrual (targeted 360, randomized 186: 94
      CAI, 92 placebo). All patients were off active treatment at time of analyses. Non
      haematologic AEs (primarily grade 1, 2) observed significantly more often in the
      CAI group included fatigue (54.5% versus 29.3%), anorexia (31.1% versus 13.0%),
      nausea (62.2% versus 30.4%), vomiting (32.2% versus 14.1%), neurosensory (60.0%
      versus 44.6%) and ataxia (33.3% versus 16.3%). Patients discontinued treatment
      for AEs, death on study or refusal more often in the CAI group (36.0% versus
      8.7%, p<0.0001). No significant differences in survival or time to progression
      were observed (median: CAI versus placebo: 11.4 months versus 10.5 months, log
      rank p=0.54; 2.8 months versus 2.4 months, log rank p=0.50). More patients
      receiving CAI reported a clinically significant (10-point) decline in QOL
      particularly on the functional (58% versus 37%, p=0.05) construct of FACT-L and
      UNISCALE (72% versus 51%, p=0.04). CONCLUSION: The addition of CAI following
      chemotherapy does not provide clinical benefit or improvement in QOL over placebo
      in advanced NSCLC.

PMID- 18045733
TI  - Demographic and clinical properties of juvenile-onset Behcet's disease: A
      controlled multicenter study.
AB  - BACKGROUND: Behcet's disease (BD) is a multisystemic inflammatory disorder of
      unknown origin. The disease usually occurs between the second and the fourth
      decades, whereas it is uncommon in children. OBJECTIVE: In this multicenter
      study, we aimed to describe the demographic and clinical features along with
      severity in juvenile- versus adult-onset BD. METHODS: Patients with initial
      symptoms at age 16 years or younger were considered as having juvenile-onset BD.
      In all, 83 patients with juvenile-onset BD (38 male and 45 female; mean age 19.6
      +/- 7.6 years) and 536 with adult-onset (>16 years) BD (293 male and 243 female;
      mean age 39.2 +/- 10.1 years) who fulfilled the classification criteria of the
      International Study Group for BD were involved in the study. RESULTS: Familial
      cases were more frequent in juvenile-onset compared with adult-onset BD (19% vs
      10.3%; P = .017). The mean age of disease onset was 12.29 +/- 3.54 years in
      juvenile-onset BD and 31.66 +/- 8.71 years in adult-onset BD. Mucocutaneous
      lesions and articular symptoms were the most commonly observed manifestations in
      both groups. The frequency of disease manifestations was not different between
      juvenile- and adult-onset BD, except neurologic and gastrointestinal involvement,
      which were higher in juvenile-onset BD than adult-onset BD (P = .027 and P =
      .024, respectively). Oral ulcer was the most common onset manifestation of both
      juvenile-onset (86.74%) and adult-onset (89.55%) BD. The frequencies of onset
      manifestations of BD were similar, except genital ulcer, which was higher in
      adult-onset BD (P = .025). LIMITATIONS: Our study consisted of patients with BD
      mainly applying to dermatology and venerology departments. Therefore, it can be
      speculated that this study includes rather a milder spectrum of the disease.
      CONCLUSIONS: Although the clinical spectrum of juvenile-onset BD seems to be
      similar to adult-onset BD, the frequency of severe organ involvement was higher.
      Because of the higher prevalence of familial cases in juvenile-onset BD, it can
      be speculated that genetic factors may favor early expression of the disease with
      severe organ involvement.

PMID- 18045734
TI  - Phakomatosis pigmentovascularis: Clinical findings in 15 patients and review of
      the literature.
AB  - INTRODUCTION: Phakomatosis pigmentovascularis (PPV) is a rare syndrome
      characterized by the association of a vascular nevus with an extensive pigmentary
      nevus. OBJECTIVE: We sought to study and evaluate clinical findings in patients
      with PPV referred to the laser department of our hospital. METHODS: We revised
      the clinical findings of 15 patients with PPV and reclassified them according to
      Happle's new classification. RESULTS: We studied 11 female patients and 4 male
      patients with a mean age of 21 years. Thirteen had phakomatosis cesioflammea, one
      cesiomarmorata, and one an unclassifiable form. Of 15 patients, 12 had nevus of
      Ota. The vascular involvement was extensive in our PPV population and 14 patients
      were affected in two or more areas. The mosaicism pattern in 13 patients was
      patchy and without a midline separation. The most frequent associations found
      were Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and melanosis oculi.
      LIMITATIONS: Limitations include the methods of case collection, that this is a
      retrospective study, and that there were a relatively small number of patients.
      CONCLUSIONS: PPV are rare syndromes with a wide variability in their clinical
      expression. Most of the publications in the literature have only reported
      isolated cases.

PMID- 18045736
TI  - Validation of the Acute Heart Failure Index.
AB  - STUDY OBJECTIVE: Validate a clinical prediction rule prognostic of short-term
      fatal and inpatient nonfatal outcomes for heart failure patients admitted through
      the emergency department. METHODS: We retrospectively studied a random cohort of
      8,384 adult patients admitted to Pennsylvania hospitals in 2003 and 2004 with a
      diagnosis of heart failure as defined by primary discharge diagnosis codes. We
      reported the proportions of inpatient death, serious medical complications before
      discharge, and 30-day death in the patients identified as low risk by the
      prediction rule. RESULTS: The prediction rule classified 1,609 (19.2%) of the
      patients as low risk. Within this subgroup, there were 12 (0.7%; 95% confidence
      interval [CI] 0.3% to 1.2%) inpatient deaths, 28 (1.7%; 95% CI 1.1% to 2.4%)
      patients survived to hospital discharge after a serious complication, and 47
      (2.9%; 95% CI 2.1% to 3.7%) patients died within 30 days of the index
      hospitalization. CONCLUSION: This prediction rule identifies a group of admitted
      heart failure patients at low risk of inpatient mortal and nonmortal
      complications. Our validation findings suggest the rule could assist physicians
      in making site-of-care decisions for this patient population and aid in analyzing
      presenting illness burden in study populations.

PMID- 18045735
TI  - Anticipatory physiological regulation in feeding biology: cephalic phase
      responses.
AB  - Anticipatory physiological regulation is an adaptive strategy that enables
      animals to respond faster to physiologic and metabolic challenges. The cephalic
      phase responses are anticipatory responses that prepare animals to digest,
      absorb, and metabolize nutrients. They enable the sensory aspects of the food to
      interact with the metabolic state of the animal to influence feeding behavior.
      The anticipatory digestive secretions and metabolic adjustments in response to
      food cues are key adaptations that affect digestive and metabolic efficiency and
      aid in controlling the resulting elevation of metabolic fuels in the blood.
      Cephalic phase responses enable digestion, metabolism, and appetite to be
      regulated in a coordinated fashion. These responses have significant effects on
      meal size. For example, if the cephalic phase insulin response is blocked the
      result is poor glucose control and smaller meals. Cephalic phase responses also
      are linked to motivation to feed, and may play a more direct role in regulating
      meal size beyond the permissive one of ameliorating negative consequences of
      feeding. For example, the orexigenic peptide ghrelin appears to display a
      cephalic phase response, rising before expected meal times. This anticipatory
      ghrelin response increases appetite; interestingly it also enhances fat
      absorption, linking appetite with digestion and metabolism.

PMID- 18045737
TI  - Core temperature cooling in healthy volunteers after rapid intravenous infusion
      of cold and room temperature saline solution.
AB  - STUDY OBJECTIVE: Studies have suggested that inducing mild hypothermia improves
      neurologic outcomes after traumatic brain injury, major stroke, traumatic
      hemorrhage, and cardiac arrest. Although infusion of cold normal saline solution
      is a simple and inexpensive method for initiating hypothermia, human cold-defense
      mechanisms potentially make this route stressful or ineffective. We hypothesize
      that rapid infusion of 30 mL/kg of cold (4 degrees C, 39.2 degrees F) 0.9% saline
      solution during 30 minutes to healthy subjects (aged 27 [standard deviation (SD)
      4] years) will reduce core body temperature to the therapeutic range of 33
      degrees C to 35 degrees C (91.4 degrees F to 95 degrees F). METHODS: Sixteen
      subjects were randomly assigned to receive either cold (4 degrees C, 39.2 degrees
      F) or room temperature (23 degrees C, 73.4 degrees F) normal saline solution.
      Subjects were not informed of their assignment, but blinding was not possible
      after initiation of the infusion. Core temperature, skin temperature, and vital
      signs were recorded every 2 minutes. Subjects indicated global discomfort during
      the infusion on a 100-mm visual analog scale at 5-minute intervals. RESULTS: Core
      temperature decreased in both the cold saline solution (1.0 degrees C [SD 0.4
      degrees C]/1.8 degrees F [0.7 degrees F]) and room temperature saline solution
      (0.5 degrees C [SD 0.1 degrees C]/0.9 degrees F [0.2 degrees F]) groups, whereas
      skin temperature was unchanged. Slopes calculated from the core temperature
      cooling curves indicate that the majority of cooling occurred during the first
      half of the infusion. Examination of the core temperature cooling curves revealed
      a 2-phase temporal pattern in 30-minute cooling curves. The early phase, spanning
      0 to 14 minutes, demonstrated rapid cooling in both groups, with a larger effect
      observed in subjects receiving cold saline solution. CONCLUSION: In this pilot
      study of healthy volunteers, rapid administration of cold saline solution to
      awake normothermic volunteers resulted in 1 degrees C (1.8 degrees F) cooling but
      did not induce a therapeutic plane of hypothermia. This change in core
      temperature was not accompanied by significant changes in skin temperature. These
      data suggest that a reduction in core temperature of about 1 degrees C (1.8
      degrees F) can be achieved in healthy humans before a thermoregulatory response
      is triggered and that rapid infusion of cold intravenous fluids is insufficient
      by itself to overcome this response. The clinically relevant control arm of room
      temperature saline solution also resulted in mild core cooling.

PMID- 18045738
TI  - Evaluation of the inhibitory effects of human serum components on bactericidal
      activity of human beta defensin 3.
AB  - Naturally occurring cationic antimicrobial peptides (CAPs) are an essential
      component of the innate immune system of multicellular organisms. At
      concentrations generally higher than those found in vivo, most CAPs exhibit
      strong antibacterial properties in vitro, but their activity may be inhibited by
      body fluids, a fact that could limit their future use as antimicrobial and/or
      immunomodulatory agents. In the present study, we evaluated the effects of human
      serum components on bactericidal activity of the human beta-defensin 3 (hBD-3), a
      CAP considered particularly promising for future therapeutic employment. Human
      serum diluted to 20% strongly inhibited the bactericidal activity of the peptide
      against both the Gram-positive species Staphylococcus aureus and the Gram
      negative species Acinetobacter baumannii. Such activity was not restored in serum
      devoid of salts (dialyzed), pre-treated with protease inhibitors, or subjected to
      both of these treatments. The addition of physiological concentrations of NaCl,
      CaCl2, and human albumin in the bactericidal assay abolished bactericidal
      activity of hBD-3 against S. aureus, while it only partially inhibited the
      activity of the peptide against A. baumannii. Although a proteolytic activity of
      serum on hBD-3 was demonstrated at the protein level by Western blot, addition of
      physiological concentrations of trypsin to the bactericidal assay only partially
      affected the antibacterial properties of the peptide. Altogether, these results
      demonstrate a major role of mono-divalent cations and serum proteins on
      inhibition of hBD-3 antibacterial properties and indicate a relative lack in
      sensitivity of the bactericidal activity of this peptide to trypsin and trypsin
      like proteases.

PMID- 18045739
TI  - Evidence for the existence of a functional Kiss1/Kiss1 receptor pathway in fish.
AB  - In mammals, the Kiss1 receptor (Kiss1r) and its kisspeptin ligands are key
      factors regulating the onset of puberty. In fish, however, the mechanisms
      underlying the initiation of puberty are poorly understood and the role of the
      Kiss1r/kisspeptin pathway in this process has not been established. In this
      study, a bioinformatics approach was used to identify the genes for Kiss1 and
      Kiss1r in five teleost genomes and the information used to clone the
      corresponding transcripts from zebrafish. Zebrafish kiss1r was expressed
      predominantly in the brain, with a minor level of expression in the eye, and
      zebrafish kiss1 was expressed in brain, intestine, adipose tissue and testis.
      Analysis of the chromosome region containing the kiss1 locus showed high synteny
      across vertebrate genomes. In contrast to their mammalian homologues, teleost
      Kiss1 protein sequences were poorly conserved with the exception of the region
      representing kisspeptin-10. Signal peptide sequences and likely cleavage and
      amidation sites in the teleost Kiss1 sequences were determined and found to be
      similar to those in mammalian Kiss1. This is the first report of the existence
      and characterization of the Kiss1 gene outside the mammalian taxa, suggesting
      that a functional Kiss1/Kiss1 receptor pathway is conserved across vertebrate
      species.

PMID- 18045743
TI  - Bioactivities of a series of phosphodiesterase type 5 (PDE-5) inhibitors as
      modelled by MIA-QSAR.
AB  - A series of cyclic guanine derivatives, phosphodiesterase type 5 (PDE-5)
      inhibitors, have been modelled using an image-based approach for quantitative
      structure-activity relationships (MIA-QSAR). The calibration model showed to be
      robust with a R(2) of 0.864 using five PLS components. The predictive ability of
      the model was tested through leave-one-out cross-validation, giving a Q(2)(CV) of
      0.605 (Q(2)(CV) improves to 0.721 after removing two outliers). An external
      validation set was also used to give an account for the modelling capability, and
      the results agreed with the ones obtained from a 3D methodology previously
      applied to this series of compounds. The method showed to be a potential tool for
      predicting new drug-like compounds, as exemplified by calculating the activities
      of two new proposed congeners derived from the training set.

PMID- 18045742
TI  - Naphthoquinoidal [1,2,3]-triazole, a new structural moiety active against
      Trypanosoma cruzi.
AB  - [1,2,3]-Triazole derivatives of nor-beta-lapachone were synthesized and assayed
      against the infective bloodstream trypomastigote form of Trypanosoma cruzi, the
      etiological agent of Chagas disease. All the derivatives were more active than
      the original quinones, with IC(50)/1 day values in the range of 17 to 359 microM,
      the apolar phenyl substituted triazole 6 being the most active compound. These
      triazole derivatives of nor-beta-lapachone emerge as interesting new lead
      compounds in drug development for Chagas disease.

PMID- 18045744
TI  - N6-1,3-diphenylurea derivatives of 2-phenyl-9-benzyladenines and 8-azaadenines:
      synthesis and biological evaluation as allosteric modulators of A2A adenosine
      receptors.
AB  - Some 1-[4-(9-benzyl-2-phenyl-9H-purin-6-ylamino)-phenyl]-3-phenyl-urea
      derivatives and some 1-[4-(9-benzyl-2-phenyl-9H-8-azapurin-6-ylamino)-phenyl]-3
      phenyl-urea derivatives were synthesised and evaluated for their interaction with
      adenosine receptors. It was found that some of these compounds can act as
      positive enhancers of agonist and antagonist radioligands for the A(2A) adenosine
      receptors. This evidence was also strengthened by functional data. Other
      compounds can act as negative modulators. Furthermore these compounds show
      inhibitory properties for A(1) and A(3) adenosine receptors.

PMID- 18045745
TI  - Synthesis of new carbon-11 labeled benzoxazole derivatives for PET imaging of 5
      HT(3) receptor.
AB  - 5-HT(3) receptor is an attractive target for the development of therapeutic
      agents for use in brain, heart and cancer diseases, and imaging agents for use in
      biomedical imaging technique PET. Benzoxazole derivatives are a novel class of 5
      HT(3) receptor partial agonists with high binding affinity. Carbon-11 labeled
      benzoxazole derivatives have been synthesized as new potential PET radioligands
      for imaging 5-HT(3) receptor. The target tracers were prepared by N
      [(11)C]methylation of their corresponding precursors using [(11)C]CH(3)OTf and
      isolated by HPLC purification procedure in 40-50% radiochemical yields, which
      were decay corrected to the end of bombardment (EOB), based on [(11)C]CO(2). The
      overall synthesis time was 20-25min from EOB. The radiochemical purity was >99%,
      and specific activity was in a range of 74-111 GBq/micromol at the end of
      synthesis (EOS).

PMID- 18045746
TI  - Preparation and antibacterial activity of cyclic 2',3'-carbamate derivatives of
      azithromycin.
AB  - In a study of the importance of a basic amino function in erythromycin derived
      antibiotics, N'-demethylazithromycin 2',3'-carbamate-11,12-carbonate has been
      prepared in six steps from (9E)-erythromycin A 9-oxime. Reactions with phosgene
      provided a cyclic carbonate from the vicinal 11,12-diol, and a cyclic 2',3'
      carbamate from the vicinal dimethylamino-alcohol moiety of the desosamine sugar.
      Further transformations provided N,N'-di(demethyl)azithromycin 2',3'-carbamate
      11,12-carbonate N-methylated at position 9a. The activity of the oxime was
      reduced in comparison with the parent azithromycin. Hence the N,N-dimethylamino
      group in the desosamine sugar is important for good antibacterial activity. The
      course of the phosgene reactions has been verified by an X-ray analysis.

PMID- 18045747
TI  - 1,8-Naphthyridines VII. New substituted 5-amino[1,2,4]triazolo[4,3
      a][1,8]naphthyridine-6-carboxamides and their isosteric analogues, exhibiting
      notable anti-inflammatory and/or analgesic activities, but no acute
      gastrolesivity.
AB  - The [1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamide derivatives 5-amino
      (2) or 5-alkoxy (3) substituted and the 5-amino[1,2,4]triazolo[4,3-a]quinoline-4
      carboxamide derivatives (4), designed to obtain new effective analgesic and/or
      anti-inflammatory agents were synthesized. Ten compounds 2 and 4 showed an
      interesting analgesic activity: the most potent ones are 2j (36% inhibition,
      P<0.05) and 4b (77% inhibition, P<0.01) at 6.25 and 25 mg kg(-1) doses,
      respectively. Compounds 2i-l and 4c showed notable anti-inflammatory properties:
      the most potent ones are 2i (68% inhibition, P<0.01) and 2l (42% inhibition,
      P<0.05) at 12.5 and 6.25 mg kg(-1) doses, respectively. The replacement in
      compounds 2 of the N-substituted 5-amino substituents with similar alkoxy groups
      usually afforded less active compounds 3.

PMID- 18045748
TI  - [A wrong rheumatoid arthritis].

PMID- 18045749
TI  - [Lumbar pain and weight loss].

PMID- 18045751
TI  - Eating habits and quality of life of patients receiving home parenteral nutrition
      in Israel.
AB  - BACKGROUND & AIMS: Using the database of an infusion provider, we assessed the
      quality of life and the eating behavior of patients receiving long-term home
      parenteral nutrition (HPN). METHODS: Fifty-one patients were recruited during a 2
      month period and anthropometric measurements, etiology of the disease and length
      of therapy were noted. A questionnaire including seven questions evaluating four
      functions was completed by a student by phone interview. The FAACT (Functional
      Assessment of Anorexia/Cachexia Therapy questionnaire) defined the response from
      grade 0 (no acceptance) to grade 4 (full acceptance) and evaluated physical,
      social/familial, emotional and functional well-being. Results are expressed as
      mean+/-S.D. or median (range) and correlation calculated using the Pearson's
      correlation test. RESULTS: Fifty patients responded to the questionnaire. Median
      length on HPN was 27.5 months (range 5-180 months). More than 56% were aged
      between 17 and 59 years, 62% suffered from an intestinal disease and less than
      10% from cancer. Ten percent were receiving HPN for >10 years. Physical activity
      was scored 1.77+/-1.11, social activity 3.18+/-0.96, emotional status 1.88+/-1.17
      and oral intake 1.95+/-0.95. Physical activity was lower in females. Physical
      activity was highly related to emotional and social status (r=0.61, p<0.0001 and
      r=0.73, p<0.0001, respectively). Social status was negatively related to
      emotional level (r=-0.43, p<0.002) while emotional status influenced oral intake
      (r=0.45, p<0.004). Age or length of therapy did not influence these factors.
      CONCLUSIONS: Patients on HPN have a low physical activity and an impaired quality
      of life despite a good social performance. Their emotional status is impaired and
      their oral intake strongly altered. These alterations are not related to time on
      therapy or age, but the highest the physical activity, the better the emotional
      and social status. We should encourage these patients to increase their physical
      activity when possible.

PMID- 18045750
TI  - [Pulmonary hyalinizing granuloma revealed by a pituitary gland diffusion].
AB  - INTRODUCTION: Pulmonary hyalinizing granuloma is a rare fibrosing lesion of the
      lung, characterized by its histological appearance which includes central whorled
      deposits of lamellar collagen. The extrapulmonary diffusion of the disease is
      extremely rare, and in our knowledge any case of pituitary diffusion has ever
      been reported in the literature. EXEGESIS: We reported an unpublished case of a
      31-year-old woman presenting with amenorrhea, galactorrhea, diplopia, headache,
      polyuria and polydipsia. The diagnosis of pulmonary hyalinizing granuloma
      revealed by an intracranial localization was based on radiologic and pathologic
      findings. Clinical course was favourable with corticotherapy. CONCLUSION: Our
      report is particular because cerebral localization was the initial manifestation
      of primary hyalinizing granuloma and because of the favourable outcome with
      corticotherapy.

PMID- 18045752
TI  - Construction and preclinical evaluation of recombinant Peru-15 expressing high
      levels of the cholera toxin B subunit as a vaccine against enterotoxigenic
      Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) is the leading cause of traveler's
      diarrhea. The heat-labile (LT) and heat-stable (ST) toxins mediate ETEC induced
      diarrhea. ETEC strains may express LT, ST, or both LT and ST, with LT-expressing
      strains accounting for approximately 50-60% of ETEC-related traveler's diarrhea.
      Cholera toxin (CT) is >80% homologous to LT and vaccination with CT-B subunit (CT
      B) -based vaccines elicit a protective immune response against LT-producing ETEC
      strains. Peru-15 is an oral, single-dose, live-attenuated cholera vaccine
      candidate that has been investigated in several clinical trials (n>400 subjects)
      and was proven well tolerated, immunogenic, and efficacious. Peru-15 was
      genetically engineered to express and secrete high levels of CT-B by cloning ctxB
      onto a glnA balanced-lethal plasmid under the transcriptional control of a strong
      constitutive promoter, resulting in Peru-15pCTB. In vitro characterization
      demonstrated that Peru-15pCTB secreted approximately 30-fold more CT-B than Peru
      15 and CT-B was stably produced after 40 generations of growth and throughout
      simulated Seed Bank and FDP (Final Drug Product) production conditions. In
      preclinical studies, the geometric mean anti-CT-B IgG titer in the sera of mice
      inoculated intranasally with two doses of Peru-15pCTB was >32-fold higher than in
      mice inoculated with Peru-15. Similarly, rabbits orally inoculated with a single
      dose of Peru-15pCTB developed titers that were approximately 30-fold higher than
      rabbits inoculated with a single dose of Peru-15. Sera from Peru-15pCTB
      vaccinated mice and rabbits neutralized LT toxicity in an in vitro assay. Peru
      15pCTB has several promising characteristics of an oral, single-dose, bivalent
      cholera/ETEC vaccine and is advancing towards a Phase 1 clinical trial.

PMID- 18045753
TI  - Declining prevalence of hepatitis B virus infection in Catalonia (Spain) 12 years
      after the introduction of universal vaccination.
AB  - AIMS: To analyze the prevalence of hepatitis B virus infection markers and
      hepatitis B vaccination in a representative sample of the juvenile and adult
      population of Catalonia and to evaluate the changes with respect to
      seroepidemiological surveys carried out in 1989 and 1996. DESIGN: In all subjects
      anti-HBc and anti-HBs antibodies and HBsAg were determined using an ELISA test.
      The possible association between sociodemographic variables and the prevalence of
      markers was analysed by calculating the adjusted odd ratio (simple logistic
      regression). SETTING: The study was carried out in 2002 in representative samples
      of the juvenile (5-14 years) and adult population (>or= 15 years) of Catalonia
      (Spain). MAIN RESULTS: In 2002 the global prevalence of HBsAg+ was 0.7% (95% CI:
      0.4-1.0) and that of anti-HBc+ 8.7% (95% CI: 7.6-9.8), values higher than those
      obtained in 1989 of 1.5% (95% CI: 1.0-2.1) and 15.6 (95% CI: 13.9-17.3). The
      prevalence of markers of infection increased with age. The only sociodemographic
      variable significantly associated with the prevalence of hepatitis B virus
      infection was the place of birth. The risk of infection was twice as high in
      subjects born outside Catalonia (p<0.01), adjusted OR 2.0 (95% CI: 1.34-2.98)
      compared with those born in Catalonia. CONCLUSIONS: The results of this study
      show that the prevalence of hepatitis B virus infection (anti-HBc+) in Catalonia
      (Spain) is currently the lowest it has ever been and suggest that there has been
      a change in the pattern of endemicity of hepatitis B virus infection in
      Catalonia, which has become a country of low endemicity.

PMID- 18045754
TI  - Phenotypic changes in the Japanese encephalitis virus after one passage in Neuro
      2a cells: generation of attenuated strains of the virus.
AB  - Live attenuated strains of the Japanese encephalitis (JE) virus are known to form
      in various cultured cells. In this study, we selected attenuated JE virus
      variants by passing the parent virus strains once through Neuro-2a cells, showing
      that the selection intensity ranged 2-1000-fold after infection for 3d. The
      selection of attenuated variants appeared in association with mutations on the
      envelope (E) glycoprotein. This is likely determined by the differential binding
      abilities of specific E proteins with highly sulfated glycosaminoglycans on the
      cell surface. A plaque-purification method showed that Neuro-2a-selected variants
      were usually less neurovirulent, leading to a longer survival time of
      intracerebrally inoculated mice. Specific selected variants (mostly with the
      small-plaque phenotype) were shown to be more efficient at replication in Vero
      cells and less virulent, particularly those with substitution of the E-138 (Glu-
      >Lys) residue. As a result, most, if not all, low-virulent variants were
      generated in a relatively short time, all which have the potential to be live
      attenuated vaccine candidates of the JE virus.

PMID- 18045755
TI  - Effect of field exposure to 38-year-old residual petroleum hydrocarbons on
      growth, condition index, and filtration rate of the ribbed mussel, Geukensia
      demissa.
AB  - In September 1969, the Florida barge spilled 700,000 L of No. 2 fuel oil into the
      salt marsh sediments of Wild Harbor, MA. Today a substantial amount,
      approximately 100 kg, of moderately degraded petroleum remains within the
      sediment and along eroding creek banks. The ribbed mussels, Geukensia demissa,
      which inhabit the salt marsh creek bank, are exposed to the spilled oil.
      Examination of short-term exposure was done with transplantation of G. demissa
      from a control site, Great Sippewissett marsh, into Wild Harbor. We also examined
      the effects of long-term exposure with transplantation of mussels from Wild
      Harbor into Great Sippewissett. Both the short- and long-term exposure
      transplants exhibited slower growth rates, shorter mean shell lengths, lower
      condition indices, and decreased filtration rates. The results add new knowledge
      about long-term consequences of spilled oil, a dimension that should be included
      when assessing oil-impacted areas and developing management plans designed to
      restore, rehabilitate, or replace impacted areas.

PMID- 18045756
TI  - Developing climatic scenarios for pesticide fate modelling in Europe.
AB  - A climatic classification for Europe suitable for pesticide fate modelling was
      constructed using a 3-stage process involving the identification of key climatic
      variables, the extraction of the dominant modes of spatial variability in those
      variables and the use of k-means clustering to identify regions with similar
      climates. The procedure identified 16 coherent zones that reflect the variability
      of climate across Europe whilst maintaining a manageable number of zones for
      subsequent modelling studies. An analysis of basic climatic parameters for each
      zone demonstrates the success of the scheme in identifying distinct climatic
      regions. Objective criteria were used to identify one representative 26-year
      daily meteorological series from a European dataset for each zone. The
      representativeness of each series was then verified against the zonal
      classifications. These new FOOTPRINT climate zones provide a state-of-the-art
      objective classification of European climate complete with representative daily
      data that are suitable for use in pesticide fate modelling.

PMID- 18045757
TI  - Timing of phosphate application affects arsenic phytoextraction by Pteris vittata
      L. of different ages.
AB  - The effects of timing in phosphate application on plant growth and arsenic
      removal by arsenic hyperaccumulator Pteris vittata L. of different ages were
      evaluated. The hydroponic experiment consisted of three plant ages (A45d, A90d
      and A180d) and three P feeding regimens (P200+0, P134+66 and P66+134) growing for
      45 d in 0.2-strength Hoagland-Arnon solution containing 145 microg L(-1) As.
      While all plants received 200 microM P, P was added in two phases: during
      acclimation and after arsenic exposure. High initial P-supply (P200+0) favored
      frond biomass production and plant P uptake, while split-P application (P134+66
      and P66+134) favored plant root production. Single P addition favored arsenic
      accumulation in the roots while split-P addition increased frond arsenic
      accumulation. Young ferns (A45d) in treatment P134+66 were the most efficient in
      arsenic removal, reducing arsenic concentration to below 10 microg L(-1) in 35 d.
      The results indicated that the use of young ferns, coupled with feeding of low
      initial P or split-P application, increased the efficiency of arsenic removal by
      P. vittata.

PMID- 18045758
TI  - Molecular biomarkers of Dreissena polymorpha for evaluation of renaturation
      success of a formerly sewage polluted stream.
AB  - The renaturation success of an urban stream, formally used for discharge of
      treated sewage waters was investigated by active biomonitoring with Dreissena
      polymorpha based on molecular biomarkers and compared to a semi-natural stream
      and laboratory controls. Response to pollution charges were analyzed by reverse
      transcriptase-PCR of heat-shock protein (hsp70), P-glycoprotein (P-gp), catalase
      (CAT) and pi class glutathione S-transferase (piGST). Hsp70 transcription was
      similarly induced at both sites, indicating protein damage. At the semi-natural
      stream CAT and P-gp were induced, indicating oxidative stress and increased
      discharge of pollutants, which correlated to high amounts of aluminum at this
      site. piGST was induced at one sampling date at the renaturated stream only, but
      identification of the causing pollutant was not achieved. Results confirm
      regeneration of the formerly sewage polluted stream, because induction of the
      tested biomarkers was either at or below the levels of the semi-natural stream.

PMID- 18045759
TI  - Distribution and sources of polycyclic aromatic hydrocarbons in surface sediments
      of rivers and an estuary in Shanghai, China.
AB  - Concentrations, spatial distribution and sources of 17 polycyclic aromatic
      hydrocarbons (PAHs) and methylnaphthalene were investigated in surface sediments
      of rivers and an estuary in Shanghai, China. Total PAH concentrations, excluding
      perylene, ranged from 107 to 1707 ng/g-dw. Sedimentary PAH concentrations of the
      Huangpu River were higher than those of the Yangtze Estuary. The concentration of
      the Suzhou River was close to the average concentration of the Huangpu River.
      PAHs source analysis suggested that, in the Yangtze Estuary, PAHs at locations
      far away from cities were mainly from petrogenic sources. At other locations,
      both petrogenic and pyrogenic inputs were significant. In the Huangpu and Suzhou
      Rivers, pyrogenic input outweighed other sources. The pyrogenic PAHs in the upper
      reaches of the Huangpu River were mainly from the incomplete combustion of grass,
      wood and coal, and those in the middle and lower reaches were from vehicle and
      vessel exhaust.

PMID- 18045760
TI  - Childhood and adolescent sexual abuse and subsequent sexual risk behavior:
      evidence from controlled studies, methodological critique, and suggestions for
      research.
AB  - Childhood and adolescent sexual abuse (CSA) is associated with a wide variety of
      adverse psychological and health outcomes, including negative sexual health
      outcomes. In this paper, we review the literature investigating the relation
      between CSA and subsequent sexual risk behaviors among men and women. Previous
      research has found a relatively consistent association between CSA and higher
      rates of sexual risk behaviors, particularly sex trading, more sexual partners,
      and an earlier age of first intercourse. However, there are a number of
      limitations to this research, including lack of a consistent definition of CSA,
      failure to investigate gender as a moderator, and possible confounding of the CSA
      experience with some of the sexual behavior outcome variables. Further, although
      there appears to be an association between CSA and later sexual risk behavior,
      researchers have not established whether this association is causal. Suggestions
      for future research and implications for clinical practice are discussed.

PMID- 18045762
TI  - Induction of cell death in RAW 264.7 cells by alpha-lactalbumin.
AB  - Alpha-lactalbumin (alpha-LA), a major human milk whey protein, has been reported
      to exhibit bactericidal properties, immune suppressive effects, anti
      proliferation and apoptosis in transformed cells; however, little is known about
      its anti-inflammation and related molecular mechanism. In this study we
      investigated the effects of alpha-LA on macrophages. We found that treatment with
      high concentration alpha-LA (> or = 100 microg/ml) could result in a time- and
      dose-dependent decrease in growth activity, morphological changes, increase in
      hypodiploid DNA population, and DNA fragmentation in RAW 264.7 cells. We also
      found that high dose alpha-LA could induce cellular apoptosis and necrosis, as
      determined by Annexin V binding assay. The alpha-LA could enhance the expression
      levels of cytochrome c, active caspase 3, active caspase 8, extracellular signal
      regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) activation without
      changing the protein levels, but suppress the protein level of Bcl-2. The broad
      spectrum caspase inhibitor, Boc-D-fmk, failed to block cell death, indicating
      that alpha-LA-induced cell death was modulated in a caspase-independent manner.
      In addition, the ERK1/2 inhibitor, PD98059, could partially rescue alpha-LA
      induced cell death, while the JNK inhibitor, SP600125, could weakly protect cells
      from death. Our results suggested that activation of ERK1/2 might mediate alpha
      LA-induced cell death in RAW 264.7 cells.

PMID- 18045761
TI  - Treatment with haloperidol and diazepam alters GABA(A) receptor density in the
      rat brain.
AB  - A significant body of data suggests that GABA(A) receptors are altered in the CNS
      of subjects with schizophrenia. However, subjects with schizophrenia are treated
      with antipsychotic drugs and, in some cases, antipsychotic drugs and
      benzodiazepines. It has therefore been suggested that the changes in GABA(A)
      receptors in the CNS of subjects with schizophrenia are due to such drug
      treatments. Surprisingly, there appear to be no studies to determine the effect
      of a combined antipsychotic-benzodiazepine treatment on GABA(A) receptors. We
      therefore measured both the GABA binding site ([3H]muscimol) and the
      benzodiazepine binding site ([3H]flumazenil) in the CNS of rats treated with
      either haloperidol, diazepam or a combination of the two drugs. The main findings
      of our study are that treatment with diazepam or the combination of diazepam and
      haloperidol results in regionally selective increases GABA binding sites but
      treatment with haloperidol alone decreases the GABA binding site in the thalamus
      but increases these sites in the hypothalamus. By contrast, treatment with
      diazepam, haloperidol and a combination of the two drugs resulted in widespread
      decreases in the number of benzodiazepine binding sites in the rat CNS. The
      notable exception to this outcome was increased numbers of benzodiazepine binding
      sites in the frontal cortex of rats that had received diazepam. Our data suggests
      that there are complex changes in the GABA(A) receptor following treatment with
      haloperidol, diazepam or a combination of these drugs. This outcome may be
      relevant to the therapeutic benefits of using both drugs in conjunction early in
      the treatment of a psychotic episode.

PMID- 18045763
TI  - Protective effect of quercetin on nicotine-induced prooxidant and antioxidant
      imbalance and DNA damage in Wistar rats.
AB  - We have investigated the protective effect of quercetin (QN) against nicotine
      induced prooxidant and antioxidant imbalance in circulation, lung, liver and
      kidney of experimental rats. The protective effect of QN was compared with N
      acetylcysteine (NAC), a well-known antioxidant. Male albino rats of Wistar stain
      were used for the experimental study. Lung toxicity was induced by subcutaneous
      injection of nicotine at a dose of 2.5mg/kg body weight (5 days a week, for 22
      weeks) and QN was given simultaneously by intragastric intubations for 22 weeks.
      The body weight gain of rats during experimental period was significantly
      decreased in nicotine treated group, whereas QN co-treated rats significantly
      increased in their body weight. The levels of lipid peroxidative indices viz.,
      thiobarbituric acid reactive substances and hydroperoxides, and nitric oxide in
      circulation, lung, liver and kidney of nicotine-treated rats were increased
      significantly when compared to normal, which were brought down to near normal in
      QN co-treated group. Endogenous antioxidant status viz., superoxide dismutase,
      catalase, glutathione peroxidase and reduced glutathione were found to be
      significantly decreased in circulation, lung, liver and kidney of nicotine
      treated group, which were significantly increased in QN-administered groups. The
      extent of DNA damage (evaluated by comet assay) was significantly increased in
      circulatory blood of nicotine-treated rats, which was effectively brought down by
      QN treatment. The protective effect of QN against nicotine toxicity was
      comparable to that of NAC. Our data suggest that QN exerts its protective effect
      by modulating the extent of lipid peroxidation and augmenting antioxidant defense
      system and thus protects the DNA in experimental animals.

PMID- 18045764
TI  - Identification of formaldehyde-responsive genes by suppression subtractive
      hybridization.
AB  - Formaldehyde is frequently used in indoor household and occupational
      environments. Inhalation of formaldehyde invokes an inflammatory response,
      including a variety of allergic signs and symptoms. Therefore, formaldehyde has
      been considered as the most prevalent cause of sick building syndrome, which has
      become a major social problem, especially in developing urban areas. Further
      formaldehyde is classified as a genotoxicant in the respiratory tract of rats and
      humans. To better understand the molecular mechanisms involved in formaldehyde
      intoxication, we sought differentially regulated genes by formaldehyde exposure
      to Hs 680.Tr human trachea cells, using polymerase chain reaction (PCR)-based
      suppression subtractive hybridization. We identified 27 different formaldehyde
      inducible genes, including those coding for the major histocompatibility complex,
      class IA, calcyclin, glutathione S-transferase pi, mouse double minute 2 (MDM2),
      platelet-derived growth factor receptor alpha, and which are known to be
      associated with cell proliferation and differentiation, immunity and
      inflammation, and detoxification. Induction of these genes by formaldehyde
      treatment was confirmed by reverse transcription PCR and western blot analysis.
      Further, the expression of calcyclin, glutathione S-transferase pi, PDGFRA and
      MDM2 were significantly induced in the tracheal epithelium of Sprague Dawley rats
      after formaldehyde inhalation. Our results suggest that the elevated levels of
      these genes may be associated with the formaldehyde-induced toxicity, and that
      they deserve evaluation as potential biomarkers for formaldehyde intoxication.

PMID- 18045765
TI  - Influence of different endodontic filling materials on root fracture
      susceptibility.
AB  - OBJECTIVE: To evaluate the influence of different endodontic materials on root
      fracture susceptibility. METHODS: Seventy-two mandibular incisors were sectioned
      1mm below the cementoenamel junction to obtain roots of 12 mm length. Roots were
      submitted to chemomechanical preparation with the rotary instruments of Profile
      system. The obturation of root canals were performed with the following filling
      materials (n=12): GI, unfilled teeth (control); GII, Endofill+gutta-percha; GIII,
      Sealer 26+gutta-percha; GIV, AH Plus+gutta-percha; GV, Epiphany+gutta-percha;
      GVI, Epiphany+Resilon. After the sealers setting time, each root was embedded in
      acrylic resin. The specimens were then submitted to fracture resistance test
      using an Instron testing machine at 1mm/min. RESULTS: The ANOVA test showed no
      significant statistical difference (p>.05) among GI (162.16+/-41.4N), GII
      (168.46+/-37.5N), GIII (164.83+/-35.7N), GIV (168.29+/-38.7N), GV (172.36+/
      20.6N) and GVI (193.11+/-42.8N). CONCLUSION: The core materials (gutta-percha or
      Resilon) combined with the tested endodontic sealers are not able to increase the
      root fracture resistance in canals submitted to chemomechanical preparation.

PMID- 18045766
TI  - Change in surface hardness of enamel by a cola drink and a CPP-ACP paste.
AB  - OBJECTIVES: This in vitro study used surface microhardness to evaluate whether a
      paste containing casein phosphopeptide amorphous calcium phosphate (CPP-ACP) can
      reharden tooth enamel softened by a cola drink, and how different saliva
      substitute solutions affect the enamel hardness. METHODS: Twenty-four bovine
      incisors, each tooth consisting of treatment and control halves, were immersed in
      a cola drink (Coke) for 8 min, then placed under a 0.4 mL/min drip with various
      saliva-substitute solutions. The saliva-substitute solutions were: saliva-like
      solution (SLS) with 1 ppm fluoride, SLS without fluoride, and Biotene mouthwash.
      CPP-ACP paste was applied to the treatment halves for 3 min at 0, 8, 24, and 36
      h. Knoop microhardness measurements were performed at baseline, after the cola
      drink immersion, and after 24 and 48 h contact with saliva-substitute solution.
      RESULTS: Enamel hardness significantly decreased after immersion in cola drink
      (ANOVA, p<0.05). After contact with saliva-like solutions for 48 h, those treated
      with CPP-ACP paste were significantly harder than those untreated regardless of
      the presence of 1 ppm fluoride in the saliva-like solution (ANOVA, p<0.05).
      Biotene mouthwash significantly softened the enamel surface (ANOVA, p<0.05). Two
      way ANOVA showed significant effects of the CPP-ACP paste application and types
      of saliva-substitute solutions on the changes in surface hardness of the softened
      enamel at a significance level of 0.05. CONCLUSION: The application of CPP-ACP
      paste with continuous replenishment of saliva-like solution for 48 h
      significantly hardened enamel softened by a cola drink. Biotene mouthwash
      softened enamel surface after 48 h contact.

PMID- 18045767
TI  - Non-redox-active small-molecules can accelerate oxidative protein folding by
      novel mechanisms.
AB  - Multi-disulfide-bond-containing proteins acquire their native structures through
      an oxidative folding reaction which involves formation of native disulfide bonds
      through thiol-disulfide exchange reactions between cysteines and disulfides
      coupled to a conformational folding event. Oxidative folding rates of the four
      disulfide-bond-containing protein bovine pancreatic ribonuclease A (RNase A) in
      the presence of the synthetic redox-active molecule, (+/-)-trans-1,2-bis(2
      mercaptoacetamido)cyclohexane (BMC), and in combination with non-redox-active
      trimethylamine-N-oxide (TMAO), and trifluorethanol were determined by HPLC
      analysis. The data indicate that regeneration of RNase A is enhanced 2-fold by
      BMC (50 microM) and 3-fold upon addition of TMAO (0.2 M) and TFE (3% v/v)
      relative to control experiments performed in the absence of small-molecules.
      Examination of the native tendency of the fully-reduced polypeptide and the
      stability of key folding intermediates suggests that the increased oxidative
      folding rate can be attributed to native-like elements induced within the fully
      reduced polypeptide and the stabilization of native-like species by added non
      redox-active molecules.

PMID- 18045768
TI  - Utility of contrast-enhanced endoscopic ultrasonography for diagnosis of small
      pancreatic carcinomas.
AB  - The aim of our study was to assess the utility of endoscopic ultrasonography
      (EUS) and contrast-enhanced EUS (CE-EUS) for the depiction and differential
      diagnosis of pancreatic tumors focusing in particularly those 2 cm or smaller. We
      compared different diagnostic procedures, contrast-enhanced multidetector
      computed tomography (CE-CT) and EUS with the use of power Doppler (PD-EUS) and CE
      EUS for detection and differential diagnosis of pancreatic tumors. The study
      included 156 consecutive patients with suspected pancreatic tumors, who underwent
      CE-CT, and EUS followed by PD-EUS and CE-EUS. CE-EUS was performed by power
      Doppler mode using sonographic contrast agent Levovist. Thirty-six of 156
      patients examined had tumors of < or =2 cm. EUS had significantly higher
      sensitivity (94.4%) for detection of pancreatic carcinomas of 2 cm or less in
      comparison to CE-CT (50%). For small pancreatic tumor of 2 cm or less,
      sensitivities for differentiating ductal carcinomas from other tumors were 50.0%,
      11.0% and 83.3% for CE-CT, PD-EUS and CE-EUS. CE-EUS was significantly more
      sensitive than PD-EUS and CE-CT. EUS and subsequent CE-EUS are more sensitive
      than CE-CT in the detection and the differentiation of small pancreatic tumors.

PMID- 18045769
TI  - Ultrasound examination is useful for prediction of histologic type in invasive
      ductal carcinoma of the breast.
AB  - The aim of this study was to estimate the histologic type of invasive ductal
      carcinoma of the breast according to the ultrasound (US) criteria and to identify
      the high-risk patients for lymph node metastases. An acceptable preoperative
      diagnosis of lymph node metastasis is essential when performing the reduction of
      lymphadenectomy. The positive relationship between histology and prognosis has
      been reported in breast cancer. However, few reports have examined the
      relationship between preoperative US findings and histology. Ultrasound
      examination was performed in 252 patients with invasive ductal carcinoma (91
      papillotubular, 54 solid-tubular and 107 scirrhous carcinoma). Risk factors for
      nodal metastasis were analyzed in clinicopathological findings. After nine
      criteria were defined based on US findings, all tumors were classified into US
      histologic type. According to the multivariate analysis, lymph node metastases
      was significantly associated with tumor size (p < 0.001), histology (p < 0.001)
      and age (p = 0.038). Histology was an important risk factor for nodal metastasis,
      especially in scirrhous carcinoma. When comparing the US classification and
      histology, the accuracy rate of US for papillotubular, solid-tubular and
      scirrhous type was 75%, 78% and 75%, respectively. To predict the scirrhous
      carcinoma with frequent nodal metastasis, US criteria such as the larger ratio of
      depth-to-width, boundary echo and attenuation of the back echo was important. It
      is important to preoperatively estimate the histologic type by tumor property
      using US. Our US classifications may be useful to pick up high-risk patients for
      nodal metastasis in invasive breast cancer.

PMID- 18045770
TI  - Postchemotherapy retroperitoneal lymph node dissection in advanced germ cell
      tumours of the testis.
AB  - OBJECTIVES: To review the role of postchemotherapy retroperitoneal lymph node
      dissection (PC-RPLND) in patients with advanced testicular germ cell tumours
      (TGCT) with special attention towards the indication, surgical technique, and
      oncological outcome. METHODS: A structured review of the literature until May
      2007 using the PubMed database was performed. RESULTS: According to current
      guidelines and recommendations, PC-RPLND in advanced seminomas with residual
      tumours is indicated only if a PET scan performed 6-8 wk after chemotherapy is
      positive. In nonseminomatous TGCT, PC-RPLND is indicated for all residual
      radiographic lesions with negative or plateauing markers. Loss of antegrade
      ejaculation represents the most common long-term complication, which can be
      prevented by a nerve-sparing or modified template resection. The relapse rate
      after PC-RPLND is around 12%; however, it increases significantly to about 45% in
      cases with redo RPLND and late relapses. Patients with increasing markers should
      undergo salvage chemotherapy. Only select patients with elevated markers who are
      thought to be chemorefractory might undergo desperation PC-RPLND if all
      radiographically visible lesions are completely resectable. CONCLUSION: PC-RPLND
      represents a major part of the management of advanced TGCT undergoing inductive
      chemotherapy. Complete resection of all residual masses after primary
      chemotherapy results in a long-term disease-free survival of 95%. PC-RPLND
      requires a complex surgical approach and should be performed in experienced,
      tertiary referral centres only.

PMID- 18045771
TI  - Editorial comment on: postchemotherapy retroperitoneal lymph node dissection in
      advanced germ cell tumors of the testis.

PMID- 18045772
TI  - Editorial comment on: postchemotherapy retroperitoneal lymph node dissection in
      advanced germ cell cancer tumors of the testis.

PMID- 18045773
TI  - Intracellular trafficking of somatostatin receptors.
AB  - The somatostatin receptor subtypes 1-5 (sst(1)-sst(5)) exhibit different
      intracellular trafficking and endosomal sorting after agonist exposure. The
      internalization of the somatostatin receptor subtypes sst(2), sst(3) and sst(5)
      occurs to a much higher extent after somatostatin exposure than of sst(1) or
      sst(4). After endocytosis, sst(2) and sst(5) recycle to the plasma membrane,
      whereas sst(3) is predominantly down-regulated. This review will focus on the
      molecular mechanisms of the differential intracellular trafficking of sst(2),
      sst(3) and sst(5), and discusses our current knowledge on somatostatin receptor
      interacting proteins.

PMID- 18045774
TI  - Adrenocortical changes and arterial hypertension in lipoatrophic A-ZIP/F-1 mice.
AB  - The A-ZIP/F-1 transgenic mouse is a model of lipoatrophic diabetes with severe
      insulin resistance, hyperglycemia and hyperlipidemia. Recently, a regulatory role
      of adipose tissue on adrenal gland function and blood pressure has been
      suggested. To further explore the importance of adipose tissue in the regulation
      of adrenal function and blood pressure, we studied this mouse model of
      lipodystrophy. A-ZIP/F-1 mice exhibit significantly elevated systolic and
      diastolic blood pressure values despite lack of white adipose tissue and its
      hormones. Furthermore, A-ZIP/F-1 lipoatrophic mice have a significant reduction
      of adrenal zona glomerulosa, while plasma aldosterone levels and aldosterone
      synthase mRNA expression remain unchanged. On the other hand, lipoatrophic mice
      present elevated corticosterone levels but no adrenocortical hyperplasia.
      Ultrastructural analysis of adrenal gland show significant alterations in
      adrenocortical cells, with conformational changes of mitochondrial internal
      membranes and high amounts of liposomes. In conclusion, lipodystrophy in A-ZIP/F
      1 mice is associated with hypertension, possibly due to hypercorticosteronemia
      and/or others metabolic-vascular changes.

PMID- 18045775
TI  - The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic
      changes in human and transgenic mouse brain and heart tissues.
AB  - Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation
      within intron 1 of the FXN gene, leading to reduced expression of frataxin
      protein. Evidence suggests that the mutation may induce epigenetic changes and
      heterochromatin formation, thereby impeding gene transcription. In particular,
      studies using FRDA patient blood and lymphoblastoid cell lines have detected
      increased DNA methylation of specific CpG sites upstream of the GAA repeat and
      histone modifications in regions flanking the GAA repeat. In this report we show
      that such epigenetic changes are also present in FRDA patient brain, cerebellum
      and heart tissues, the primary affected systems of the disorder. Bisulfite
      sequence analysis of the FXN flanking GAA regions reveals a shift in the FRDA DNA
      methylation profile, with upstream CpG sites becoming consistently
      hypermethylated and downstream CpG sites becoming consistently hypomethylated. We
      also identify differential DNA methylation at three specific CpG sites within the
      FXN promoter and one CpG site within exon 1. Furthermore, we show by chromatin
      immunoprecipitation analysis that there is overall decreased histone H3K9
      acetylation together with increased H3K9 methylation of FRDA brain tissue.
      Further studies of brain, cerebellum and heart tissues from our GAA repeat
      expansion-containing FRDA YAC transgenic mice reveal comparable epigenetic
      changes to those detected in FRDA patient tissue. We have thus developed a mouse
      model that will be a valuable resource for future therapeutic studies targeting
      epigenetic modifications of the FXN gene to increase frataxin expression.

PMID- 18045776
TI  - Transcriptional activators HAP/NF-Y rescue a cytochrome c oxidase defect in yeast
      and human cells.
AB  - Cell survival and energy production requires a functional mitochondrial
      respiratory chain. Biogenesis of cytochrome c oxidase (COX), the last enzyme of
      the mitochondrial respiratory chain, is a very complicated process and requires
      the assistance of a large number of accessory factors. Defects in COX assembly
      alter cellular respiration and produce severe human encephalomyopathies.
      Mutations in SURF1, a COX assembly factor of exact unknown function, produce
      Leigh's syndrome (LS), the most frequent cause of COX deficiency in infants. In
      the yeast Saccharomyces cerevisiae, deletion of the SURF1 homologue SHY1 results
      in a similar COX deficiency. In order to identify genetic modifiers of the shy1
      mutant phenotype, we have explored for genetic interactions involving SHY1. Here
      we report that overexpression of Hap4p, the catalytic subunit of the CCAAT
      binding transcriptional activator Hap2/3/4/5p complex, suppresses the respiratory
      defect of yeast shy1 mutants by increasing the expression of nuclear-encoded COX
      subunits that interact with the mitochondrially encoded Cox1p. Analogously,
      overexpression of the Hap complex human homologue NF-YA/B/C transcription complex
      in SURF1-deficient fibroblasts from an LS patient efficiently rescues their COX
      deficiency.

PMID- 18045777
TI  - A network of dopaminergic gene variations implicated as risk factors for
      schizophrenia.
AB  - We evaluated the hypothesis that dopaminergic polymorphisms are risk factors for
      schizophrenia (SZ). In stage I, we screened 18 dopamine-related genes in two
      independent US Caucasian samples: 150 trios and 328 cases/501 controls. The most
      promising associations were detected with SLC6A3 (alias DAT), DRD3, COMT and
      SLC18A2 (alias VMAT2). In stage II, we comprehensively evaluated these four genes
      by genotyping 68 SNPs in all 478 cases and 501 controls from stage I. Fifteen
      (23.1%) significant associations were found (p < or = 0.05). We sought epistasis
      between pairs of SNPs providing evidence of a main effect and observed 17
      significant interactions (169 tests); 41.2% of significant interactions involved
      rs3756450 (5' near promoter) or rs464049 (intron 4) at SLC6A3. In stage III, we
      confirmed our findings by genotyping 65 SNPs among 659 Bulgarian trios. Both
      SLC6A3 variants implicated in the US interactions were overtransmitted in this
      cohort (rs3756450, p = 0.035; rs464049, p = 0.011). Joint analyses from stages II
      and III identified associations at all four genes (p(joint) < 0.05). We tested 29
      putative interactions from stage II and detected replication between seven locus
      pairs (p < or = 0.05). Simulations suggested our stage II and stage III
      interaction results were unlikely to have occurred by chance (p = 0.008 and
      0.001, respectively). In stage IV we evaluated rs464049 and rs3756450 for
      functional effects and found significant allele-specific differences at rs3756450
      using electrophoretic mobility shift assays and dual-luciferase promoter assays.
      Our data suggest that a network of dopaminergic polymorphisms increase risk for
      SZ.

PMID- 18045778
TI  - Chemotherapy induced diarrhea.
AB  - PURPOSE: To provide a current review of the literature related to chemotherapy
      induced diarrhea (CID), including clinical assessment, recommended management
      guidelines and investigational pharmacological approaches for the prevention and
      treatment of CID. DATA SOURCES: A search of MEDLINE, PubMed, EMBASE, Cochrane
      Library, International Pharmaceutical Abstracts, and Web of Science (1996-2006)
      databases was conducted using terms such as: chemotherapy, diarrhea, diarrhoea,
      and irinotecan. Appropriate references from selected articles were also used. The
      search engine, Google, provided further access to information. DATA EXTRACTION:
      The retrieved literature was reviewed to include all articles pertaining to the
      pathophysiology, assessment and management of CID. DATA SYNTHESIS: Diarrhea is a
      debilitating and potentially life-threatening side effect associated with many
      chemotherapeutic agents. Despite the high incidence and severity of CID, it is
      often under recognized and poorly managed. A multidisciplinary panel recently
      updated recommended practice guidelines for the assessment and management of CID.
      Prompt and aggressive intervention is important in order to minimize the negative
      consequences of CID, such as dehydration, which may cause interruptions in
      optimal clinical outcomes or may lead to life-threatening sequelae. Further
      investigation into the pathophysiology of CID may allow for more directed
      approaches in the prophylaxis and treatment of CID.

PMID- 18045779
TI  - Overview of targeted therapies in oncology.
AB  - BACKGROUND: Recent scientific advances have provided a map of the human genome
      along with a better understanding of the processes that transform healthy cells
      into diseased cells. This has led to the emergence of a new class of drugs called
      targeted therapies. OBJECTIVE: To describe the classifications and basic
      pharmacology of targeted therapies. METHODS: A literature search was performed
      for peer reviewed journal articles using Medline (1996-2007), Embase (1996-2007)
      and Google. The search was performed using keywords such as angiogenesis
      inhibitors, cancer vaccines, gene therapy, monoclonal antibodies, small
      molecules, proteasome inhibitors, targeted therapy and tyrosine kinase
      inhibitors. CONCLUSIONS: A review of the basic pharmacology is described in this
      article, including the following major categories of targeted therapies: * Small
      molecule drugs * Monoclonal antibodies * Apoptosis-inducing drugs * Angiogenesis
      Inhibitors * Cancer vaccines * Gene therapy.

PMID- 18045780
TI  - Therapeutic drug monitoring of cancer chemotherapy.
AB  - Therapeutic drug monitoring is not routinely used for chemotherapy agents. There
      are Several reasons, but one major drawback is the lack of established
      therapeutic Concentration ranges. Combination chemotherapy makes the
      establishment of Therapeutic ranges for individual drugs difficult, the
      concentration-effect relationship for a single drug may not be the same as when
      that drug is used in a drug combination. Pharmacokinetic optimization protocols
      for many classes of cytotoxic compounds exist in specialized centers, and some of
      these protocols are now part of large multicentre trials. Nonetheless, TDM
      clearly has the potential to improve the clinical use of chemotherapy gents, most
      of which have very narrow therapeutic indices and highly variable
      pharmacokinetics. A substantial body of literature accumulating during the past
      15 years demonstrates relationships between systemic exposure to various
      chemotherapy agents and their toxic or therapeutic effects. This article reviews
      TDM concepts in addition to tools based on pharmacokinetic modeling of
      chemotherapy agents. The administered dose of chemotherapy agents is sometimes
      adjusted individually using either a priori or a posteriori methods. These models
      can only be applied by using the same dose and schedule as the original study.
      Bayesian estimation offers more flexibility in blood sampling times and, owing to
      its precision and to the amount of information provided is the method of choice
      for ensuring that a given patient benefits from the desired systemic exposure.
      Moreover, the role and application of Pharmacogenetics as a tool for
      individualizing chemotherapy is discussed highlighting the agents and mechanisms
      that have been well studied and defined and their relevance to clinical practice.
      Finally, this paper address issues critical to the optimal use of TDM in a
      clinical setting, and the role of clinical pharmacist in this regard. In
      addition, it discusses future developments in this field that can contribute to
      improving cancer chemotherapy In terms of patient outcome and survival.

PMID- 18045781
TI  - Significance and impact of bisphosphonate-induced acute phase responses.
AB  - BACKGROUND: Bisphosphonates are synthetic analogs of inorganic pyrophosphates
      with high avidity for bone, where they bind to hydroxyapatite crystals.
      Bisphosphonates are effective in decreasing bone resorption, the incidence of
      skeletal-related events, and pain from bone metastases. These agents have
      recently become incorporated into the treatment regimen of patients with
      osteolytic and osteoblastic metastatic bone disease. Although relatively well
      tolerated, the initial dose(s) of intravenous aminobisphosphonates can be
      associated with an acute phase response, a nonspecific physiologic reaction
      associated with increased levels of inflammatory cytokines, fever, and flu like
      symptoms including fatigue, nausea, and myalgia. OBJECTIVE: The purpose of this
      article is to provide an updated review of the literature in this field. DATA
      SOURCE: A search of PubMed was performed using the key terms bisphosphonate,
      acute phase response, and cancer, and limited to publications in English. The
      published literature on acute phase response with bisphosphonate therapy was
      reviewed. RESULTS AND CONCLUSIONS: Approximately 40% of patients receiving
      aminobisphosphonates experience an acute phase response, which generally occurs
      only on first exposure to the drug and typically last <72 h. Not all
      bisphosphonates induce acute phase responses to the same extent. This article
      reviews acute phase response in patients with metastatic bone disease treated
      with aminobisphosphonates.

PMID- 18045782
TI  - Photostability of parenteral chemotheraphy admixtures.

PMID- 18045783
TI  - Oxaliplatin-induced hypersensitivity reaction displaying marked elevation of
      immunoglobulin E.
AB  - A 74-year-old female has been diagnosed with stage IIIB rectal cancer in 2003.
      Following anterior resection, she received adjuvant chemotherapy with three
      different regimens. In August 2005, she was started on a modified FOLFOX6
      regimen, and the sixth cycle of chemotherapy induced a severe hypersensitivity
      reaction (HSR). Immediate cessation of the infusion resulted in a disappearance
      of the allergic reaction 60 min later. Blood tests just after the reaction
      demonstrated a marked elevation of immunoglobulin E to 300 IU L(-1) (normal
      range: <170 IU L(-1)). This change implies the involvement of a type I reaction
      in the HSR. In addition, a drug lymphocyte stimulating test against oxaliplatin
      and levofolinate calcium (an isomer of leucovorin calcium) gave values of 696%
      and 107 % respectively, as compared with control serum. This suggests that the
      patient had an adverse reaction not only of type I but partly of type IV allergic
      reaction also. Oxaliplatin appears to have caused a HSR in this Japanese patient,
      and thus pharmacists, physicians, and other medical staff must keep a careful
      watch of a patient's clinical condition during chemotherapy including
      oxaliplatin.

PMID- 18045784
TI  - Interaction between mercaptopurine and milk.
AB  - Mercaptopurine is a purine analog used for acute lymphoblatic leukemia and
      chronic myelogenous leukemias. Since it is inactivated by xanthine oxidase (XO),
      concurrent intake of substances containing XO may potentially reduce
      bioavailability of mercaptopurine. Cow's milk is known to contain a high level of
      XO. In vitro and in vivo data suggest that concurrent intake of cow's milk may
      reduce the bioavailability of mercaptopurine. This interaction may be clinically
      significant. Therefore most patients should try to separate the timing of taking
      mercaptopurine and drinking milk.

PMID- 18045785
TI  - GRSDB2 and GRS_UTRdb: databases of quadruplex forming G-rich sequences in pre
      mRNAs and mRNAs.
AB  - G-quadruplex motifs in the RNA play significant roles in key cellular processes
      and human disease. While sequences capable of forming G-quadruplexes in the pre
      mRNA are involved in regulation of polyadenylation and splicing events in
      mammalian transcripts, the G-quadruplex motifs in the UTRs may help regulate mRNA
      expression. GRSDB2 is a second-generation database containing information on the
      composition and distribution of putative Quadruplex-forming G-Rich Sequences
      (QGRS) mapped in approximately 29 000 eukaryotic pre-mRNA sequences, many of
      which are alternatively processed. The data stored in the GRSDB2 is based on
      computational analysis of NCBI Entrez Gene entries with the help of an improved
      version of the QGRS Mapper program. The database allows complex queries with a
      wide variety of parameters, including Gene Ontology terms. The data is displayed
      in a variety of formats with several additional computational capabilities. We
      have also developed a new database, GRS_UTRdb, containing information on the
      composition and distribution patterns of putative QGRS in the 5'- and 3'-UTRs of
      eukaryotic mRNA sequences. The goal of these experiments has been to build freely
      accessible resources for exploring the role of G-quadruplex structure in
      regulation of gene expression at post-transcriptional level. The databases can be
      accessed at the G-Quadruplex Resource Site at:
      http://bioinformatics.ramapo.edu/GQRS/.

PMID- 18045786
TI  - EndoNet: an information resource about regulatory networks of cell-to-cell
      communication.
AB  - EndoNet is an information resource about intercellular regulatory communication.
      It provides information about hormones, hormone receptors, the sources (i.e.
      cells, tissues and organs) where the hormones are synthesized and secreted, and
      where the respective receptors are expressed. The database focuses on the
      regulatory relations between them. An elementary communication is displayed as a
      causal link from a cell that secretes a particular hormone to those cells which
      express the corresponding hormone receptor and respond to the hormone. Whenever
      expression, synthesis and/or secretion of another hormone are part of this
      response, it renders the corresponding cell an internal node of the resulting
      network. This intercellular communication network coordinates the function of
      different organs. Therefore, the database covers the hierarchy of cellular
      organization of tissues and organs as it has been modeled in the Cytomer
      ontology, which has now been directly embedded into EndoNet. The user can query
      the database; the results can be used to visualize the intercellular information
      flow. A newly implemented hormone classification enables to browse the database
      and may be used as alternative entry point. EndoNet is accessible at:
      http://endonet.bioinf.med.uni-goettingen.de/.

PMID- 18045787
TI  - The universal protein resource (UniProt).
AB  - The Universal Protein Resource (UniProt) provides a stable, comprehensive, freely
      accessible, central resource on protein sequences and functional annotation. The
      UniProt Consortium is a collaboration between the European Bioinformatics
      Institute (EBI), the Protein Information Resource (PIR) and the Swiss Institute
      of Bioinformatics (SIB). The core activities include manual curation of protein
      sequences assisted by computational analysis, sequence archiving, development of
      a user-friendly UniProt website, and the provision of additional value-added
      information through cross-references to other databases. UniProt is comprised of
      four major components, each optimized for different uses: the UniProt
      Knowledgebase, the UniProt Reference Clusters, the UniProt Archive and the
      UniProt Metagenomic and Environmental Sequences database. UniProt is updated and
      distributed every three weeks, and can be accessed online for searches or
      download at http://www.uniprot.org.

PMID- 18045788
TI  - The formation pathway of tetramolecular G-quadruplexes.
AB  - Oligonucleotides containing guanosine stretches associate into tetrameric
      structures stabilized by monovalent ions. In order to describe the sequence of
      reactions leading to association of four identical strands, we measured by NMR
      the formation and dissociation rates of (TGnT)4 quadruplexes (n = 3-6), their
      dissociation constants and the reaction orders for quadruplex formation. The
      quadruplex formation rates increase with the salt concentration but weakly depend
      on the nature (K+, Na+ or Li+) of the counter ions. The activation energies for
      quadruplex formation are negative. The quadruplex lifetimes strongly increase
      with the G-tract length and are much more longer in K+ solution than in Na+ or
      Li+ solutions. The reaction order for quadruplex formation is 3 in 0.125 M KCl
      and 4 in LiCl solutions. The kinetics measurements suggest that quadruplex
      formation proceeds step by step via sequential strand association into duplex and
      triplex intermediate species. Triplex formation is rate limiting in 0.125 M KCl
      solution. In LiCl, each step of the association process depends on the strand
      concentration. Parallel reactions to formation of the fully matched canonical
      quadruplex may result in kinetically trapped mismatched quadruplexes making the
      canonical quadruplex practically inaccessible in particular at low temperature in
      KCl solution.

PMID- 18045789
TI  - Chromatin-associated HMG-17 is a major regulator of homeodomain transcription
      factor activity modulated by Wnt/beta-catenin signaling.
AB  - Homeodomain (HD) transcriptional activities are tightly regulated during
      embryogenesis and require protein interactions for their spatial and temporal
      activation. The chromatin-associated high mobility group protein (HMG-17) is
      associated with transcriptionally active chromatin, however its role in
      regulating gene expression is unclear. This report reveals a unique strategy in
      which, HMG-17 acts as a molecular switch regulating HD transcriptional activity.
      The switch utilizes the Wnt/beta-catenin signaling pathway and adds to the
      diverse functions of beta-catenin. A high-affinity HMG-17 interaction with the
      PITX2 HD protein inhibits PITX2 DNA-binding activity. The HMG-17/PITX2 inactive
      complex is concentrated to specific nuclear regions primed for active
      transcription. beta-Catenin forms a ternary complex with PITX2/HMG-17 to switch
      it from a repressor to an activator complex. Without beta-catenin, HMG-17 can
      physically remove PITX2 from DNA to inhibit its transcriptional activity. The
      PITX2/HMG-17 regulatory complex acts independently of promoter targets and is a
      general mechanism for the control of HD transcriptional activity. HMG-17 is
      developmentally regulated and its unique role during embryogenesis is revealed by
      the early embryonic lethality of HMG-17 homozygous mice. This mechanism provides
      a new role for canonical Wnt/beta-catenin signaling in regulating HD
      transcriptional activity during development using HMG-17 as a molecular switch.

PMID- 18045790
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 available
      through NCBI's web site. NCBI resources include Entrez, the Entrez Programming
      Utilities, My NCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy
      Browser, BLAST, BLAST Link, Electronic PCR, OrfFinder, Spidey, Splign, RefSeq,
      UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genome,
      Genome Project and related tools, the Trace, Assembly, and Short Read Archives,
      the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups,
      Influenza Viral Resources, HIV-1/Human Protein Interaction Database, Gene
      Expression Omnibus, Entrez Probe, GENSAT, Database of Genotype and Phenotype,
      Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the
      Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain
      Architecture Retrieval Tool and the PubChem suite of small molecule databases.
      Augmenting the web applications are custom implementations of the BLAST program
      optimized to search specialized data sets. These resources can be accessed
      through the NCBI home page at www.ncbi.nlm.nih.gov.

PMID- 18045791
TI  - An atmospheric perspective on North American carbon dioxide exchange:
      CarbonTracker.
AB  - We present an estimate of net CO(2) exchange between the terrestrial biosphere
      and the atmosphere across North America for every week in the period 2000 through
      2005. This estimate is derived from a set of 28,000 CO(2) mole fraction
      observations in the global atmosphere that are fed into a state-of-the-art data
      assimilation system for CO(2) called CarbonTracker. By design, the surface fluxes
      produced in CarbonTracker are consistent with the recent history of CO(2) in the
      atmosphere and provide constraints on the net carbon flux independent from
      national inventories derived from accounting efforts. We find the North American
      terrestrial biosphere to have absorbed -0.65 PgC/yr (1 petagram = 10(15) g;
      negative signs are used for carbon sinks) averaged over the period studied,
      partly offsetting the estimated 1.85 PgC/yr release by fossil fuel burning and
      cement manufacturing. Uncertainty on this estimate is derived from a set of
      sensitivity experiments and places the sink within a range of -0.4 to -1.0
      PgC/yr. The estimated sink is located mainly in the deciduous forests along the
      East Coast (32%) and the boreal coniferous forests (22%). Terrestrial uptake fell
      to -0.32 PgC/yr during the large-scale drought of 2002, suggesting sensitivity of
      the contemporary carbon sinks to climate extremes. CarbonTracker results are in
      excellent agreement with a wide collection of carbon inventories that form the
      basis of the first North American State of the Carbon Cycle Report (SOCCR), to be
      released in 2007. All CarbonTracker results are freely available at
      http://carbontracker.noaa.gov.

PMID- 18045792
TI  - A T-cell receptor associated with naturally occurring human tumor immunity.
AB  - The onconeural antigens appear to serve as tumor rejection antigens in the
      paraneoplastic neurologic disorders. Here, we used an unbiased peptide binding
      screen, followed by studies in HLA-A2.1 transgenic mice to identify naturally
      processed HLA-A2.1 restricted epitopes of the paraneoplastic cerebellar
      degeneration breast/ovarian cancer antigen cdr2. These mice were used to clone
      high-avidity cdr2-specific CD8(+) T cells that recognize human tumor cells
      presenting endogenously loaded MHC class I-cdr2 peptide. T cells with this
      specificity were detected in the peripheral blood of two HLA-A2.1(+)
      paraneoplastic cerebellar degeneration patients. We cloned T cell receptor (TCR)
      alpha and beta genes from cdr2-specific T cells; electroporation of RNA encoding
      this TCR turned nonreactive donor T cells into efficient killers of human cdr2
      expressing tumor cells. Cloned cdr2-specific TCR genes provide a clinically
      relevant means for immunologic targeting of human gynecologic cancers.

PMID- 18045793
TI  - Pattern selection in plants: coupling chemical dynamics to surface growth in
      three dimensions.
AB  - BACKGROUND AND AIMS: A study is made by computation of the interplay between the
      pattern formation of growth catalysts on a plant surface and the expansion of the
      surface to generate organismal shape. Consideration is made of the localization
      of morphogenetically active regions, and the occurrence within them of symmetry
      breaking processes such as branching from an initially dome-shaped tip or
      meristem. Representation of a changing and growing three-dimensional shape is
      necessary, as two-dimensional work cannot distinguish, for example, formation of
      an annulus from dichotomous branching. METHODS: For the formation of patterns of
      chemical concentrations, the Brusselator reaction-diffusion model is used,
      applied on a hemispherical shell and generating patterns that initiate as surface
      spherical harmonics. The initial shape is hemispherical, represented as a mesh of
      triangles. These are combined into finite elements, each made up of all the
      triangles surrounding each node. Chemical pattern is converted into shape change
      by moving nodes outwards according to the concentration of growth catalyst at
      each, to relieve misfits caused by area increase of the finite element. New
      triangles are added to restore the refinement of the mesh in rapidly growing
      regions. KEY RESULTS: The postulated mechanism successfully generates: tip growth
      (or stalk extension by an apical meristem) to ten times original hemisphere
      height; tip flattening and resumption of apical advance; and dichotomous
      branching and higher-order branching to make whorled structures. Control of the
      branching plane in successive dichotomous branchings is tackled with partial
      success and clarification of the issues. CONCLUSIONS: The representation of a
      growing plant surface in computations by an expanding mesh that has no artefacts
      constraining changes of shape and symmetry has been achieved. It is shown that
      one type of pattern-forming mechanism, Turing-type reaction-diffusion, acting
      within a surface to pattern a growth catalyst, can generate some of the most
      important types of morphogenesis in plant development.

PMID- 18045794
TI  - The derivation of sink functions of wheat organs using the GREENLAB model.
AB  - BACKGROUND AND AIMS: In traditional crop growth models assimilate production and
      partitioning are described with empirical equations. In the GREENLAB functional
      structural model, however, allocation of carbon to different kinds of organs
      depends on the number and relative sink strengths of growing organs present in
      the crop architecture. The aim of this study is to generate sink functions of
      wheat (Triticum aestivum) organs by calibrating the GREENLAB model using a
      dedicated data set, consisting of time series on the mass of individual organs
      (the 'target data'). METHODS: An experiment was conducted on spring wheat
      (Triticum aestivum, 'Minaret'), in a growth chamber from, 2004 to, 2005. Four
      harvests were made of six plants each to determine the size and mass of
      individual organs, including the root system, leaf blades, sheaths, internodes
      and ears of the main stem and different tillers. Leaf status (appearance,
      expansion, maturity and death) of these 24 plants was recorded. With the
      structures and mass of organs of four individual sample plants, the GREENLAB
      model was calibrated using a non-linear least-square-root fitting method, the aim
      of which was to minimize the difference in mass of the organs between measured
      data and model output, and to provide the parameter values of the model (the sink
      strengths of organs of each type, age and tiller order, and two empirical
      parameters linked to biomass production). KEY RESULTS AND CONCLUSIONS: The masses
      of all measured organs from one plant from each harvest were fitted
      simultaneously. With estimated parameters for sink and source functions, the
      model predicted the mass and size of individual organs at each position of the
      wheat structure in a mechanistic way. In addition, there was close agreement
      between experimentally observed and simulated values of leaf area index.

PMID- 18045795
TI  - Relationships between photosynthetic activity and silica accumulation with ages
      of leaf in Sasa veitchii (Poaceae, Bambusoideae).
AB  - BACKGROUND AND AIMS: Bamboos have long-lived, evergreen leaves that continue to
      accumulate silica throughout their life. Silica accumulation has been suggested
      to suppress their photosynthetic activity. However, nitrogen content per unit
      leaf area (N(area)), an important determinant of maximum photosynthetic capacity
      per unit leaf area (P(max)), decreases as leaves age and senescence. In many
      species, P(max) decreases in parallel with the leaf nitrogen content. It is
      hypothesized that if silica accumulation affects photosynthesis, then P(max)
      would decrease faster than N(area), leading to a decrease in photosynthetic rate
      per unit leaf nitrogen (photosynthetic nitrogen use efficiency, PNUE) with
      increasing silica content in leaves. METHODS: The hypothesis was tested in leaves
      of Sasa veitchii, which have a life span of 2 years and accumulate silica up to
      41 % of dry mass. Seasonal changes in P(max), stomatal conductance, N(area) and
      silica content were measured for leaves of different ages. KEY RESULTS: Although
      P(max) and PNUE were negatively related with silica content across leaves of
      different ages, the relationship between PNUE and silica differed depending on
      leaf age. In second-year leaves, PNUE was almost constant although there was a
      large increase in silica content, suggesting that leaf nitrogen was a primary
      factor determining the variation in P(max) and that silica accumulation did not
      affect photosynthesis. PNUE was strongly and negatively correlated with silica
      content in third-year leaves, suggesting that silica accumulation affected
      photosynthesis of older leaves. CONCLUSIONS: Silica accumulation in long-lived
      leaves of bamboo did not affect photosynthesis when the silica concentration of a
      leaf was less than 25 % of dry mass. Silica may be actively transported to
      epidermal cells rather than chlorenchyma cells, avoiding inhibition of CO2
      diffusion from the intercellular space to chloroplasts. However, in older leaves
      with a larger silica content, silica was also deposited in chlorenchyma cells,
      which may relate to the decrease in PNUE.

PMID- 18045796
TI  - Variations in occupational exposure to magnetic fields among welders in Malaysia.
AB  - This study attempted to estimate the lifelong magnetic field (MF) exposures of a
      particular group of welders. Exposure was quantified via measurements,
      observations and interviews. It was found that these welders face a vast range of
      lifelong MF exposures depending on the welding processes and duration of the
      welding tasks performed. This may explain the inconsistency in the results of
      studies of MF exposures on human health. The mere assessing of the MF exposure
      levels through spot measurements does not give an overall picture of the total
      amount of exposure received by the welders as some of these workers performed the
      welding task throughout the day, whereas others performed this as a part of their
      job. The exposure to various chemicals in the fume may complicate the
      interpretation of the elevated health risk among the welders.

PMID- 18045797
TI  - Time for unification of CT dosimetry with radiography and fluoroscopy.

PMID- 18045798
TI  - Comparison of dose estimation from occupational exposure to 239Pu using different
      modelling approaches.
AB  - Several approaches are available for bioassay interpretation when assigning Pu
      doses to Mayak workers. First, a conventional approach is to apply ICRP models
      per se. An alternative method involves individualised fitting of bioassay data
      using Bayesian statistical methods. A third approach is to develop an independent
      dosimetry system for Mayak workers by adapting ICRP models using a dataset of
      available bioassay measurements for this population. Thus, a dataset of 42 former
      Mayak workers, who died of non-radiation effects, with both urine bioassay and
      post-mortem tissue data was used to test these three approaches. All three
      approaches proved to be adequate for bioassay and tissue interpretation, and thus
      for Pu dose reconstruction purposes. However, large discrepancies are observed in
      the resulting quantitative dose estimates. These discrepancies can, in large
      part, be explained by differences in the interpretation of Pu behaviour in the
      lungs in the context of ICRP lung model. Thus, a careful validation of Pu lung
      dosimetry model is needed in Mayak worker dosimetry systems.

PMID- 18045799
TI  - Evaluation of scattering factor values for internal dose assessment following the
      IDEAS guidelines: preliminary results.
AB  - The IDEAS Guidelines for the assessment of internal doses from monitoring data
      suggest default measurement uncertainties (i.e. scattering factors, SFs) to be
      used for different types of monitoring data. However, these default values were
      mainly based upon expert judgement. In this paper, SF values have been calculated
      for different radionuclides and types of monitoring data using real data
      contained in the IDEAS Internal Contamination Database. Results are presented.

PMID- 18045800
TI  - Quantitative proteomics analysis demonstrates post-transcriptional regulation of
      embryonic stem cell differentiation to hematopoiesis.
AB  - Embryonic stem (ES) cells can differentiate in vitro to produce the endothelial
      and hematopoietic precursor, the hemangioblasts, which are derived from the
      mesoderm germ layer. Differentiation of Bry(GFP/+) ES cell to hemangioblasts can
      be followed by the expression of the Bry(GFP/+) and Flk1 genes. Proteomic and
      transcriptomic changes during this differentiation process were analyzed to
      identify mechanisms for phenotypic change during early differentiation. Three
      populations of differentiating Bry(GFP) ES cells were obtained by flow cytometric
      sorting, GFP-Flk1- (epiblast), GFP+Flk1- (mesoderm), and GFP+Flk1+
      (hemangioblast). Microarray analyses and relative quantification two-dimensional
      LCLC-MS/MS on nuclear extracts were performed. We identified and quantified 2389
      proteins, 1057 of which were associated to their microarray probe set. These
      included a variety of low abundance transcription factors, e.g. UTF1, Sox2, Oct4,
      and E2F4, demonstrating a high level of proteomic penetrance. When paired
      comparisons of changes in the mRNA and protein expression levels were performed
      low levels of correlation were found. A strong correlation between isobaric tag
      derived relative quantification and Western blot analysis was found for a number
      of nuclear proteins. Pathway and ontology analysis identified proteins known to
      be involved in the regulation of stem cell differentiation, and proteins with no
      described function in early ES cell development were also shown to change
      markedly at the proteome level only. ES cell development is regulated at the mRNA
      and protein level.

PMID- 18045801
TI  - Highly efficient classification and identification of human pathogenic bacteria
      by MALDI-TOF MS.
AB  - Accurate and rapid identification of pathogenic microorganisms is of critical
      importance in disease treatment and public health. Conventional work flows are
      time-consuming, and procedures are multifaceted. MS can be an alternative but is
      limited by low efficiency for amino acid sequencing as well as low
      reproducibility for spectrum fingerprinting. We systematically analyzed the
      feasibility of applying MS for rapid and accurate bacterial identification.
      Directly applying bacterial colonies without further protein extraction to MALDI
      TOF MS analysis revealed rich peak contents and high reproducibility. The MS
      spectra derived from 57 isolates comprising six human pathogenic bacterial
      species were analyzed using both unsupervised hierarchical clustering and
      supervised model construction via the Genetic Algorithm. Hierarchical clustering
      analysis categorized the spectra into six groups precisely corresponding to the
      six bacterial species. Precise classification was also maintained in an
      independently prepared set of bacteria even when the numbers of m/z values were
      reduced to six. In parallel, classification models were constructed via Genetic
      Algorithm analysis. A model containing 18 m/z values accurately classified
      independently prepared bacteria and identified those species originally not used
      for model construction. Moreover bacteria fewer than 10(4) cells and different
      species in bacterial mixtures were identified using the classification model
      approach. In conclusion, the application of MALDI-TOF MS in combination with a
      suitable model construction provides a highly accurate method for bacterial
      classification and identification. The approach can identify bacteria with low
      abundance even in mixed flora, suggesting that a rapid and accurate bacterial
      identification using MS techniques even before culture can be attained in the
      near future.

PMID- 18045802
TI  - Stable isotope labeling by amino acids in cell culture (SILAC) and proteome
      quantitation of mouse embryonic stem cells to a depth of 5,111 proteins.
AB  - Embryonic stem (ES) cells are pluripotent cells isolated from mammalian
      preimplantation embryos. They are capable of differentiating into all cell types
      and therefore hold great promise in regenerative medicine. Here we show that
      murine ES cells can be fully SILAC (stable isotope labeling by amino acids in
      cell culture)-labeled when grown feeder-free during the last phase of cell
      culture. We fractionated the SILAC-labeled ES cell proteome by one-dimensional
      gel electrophoresis and by isoelectric focusing of peptides. High resolution
      analysis on a linear ion trap-orbitrap instrument (LTQ-Orbitrap) at sub-ppm mass
      accuracy resulted in confident identification and quantitation of more than 5,000
      distinct proteins. This is the largest quantified proteome reported to date and
      contains prominent stem cell markers such as OCT4, NANOG, SOX2, and UTF1 along
      with the embryonic form of RAS (ERAS). We also quantified the proportion of the
      ES cell proteome present in cytosolic, nucleoplasmic, and membrane/chromatin
      fractions. We compared two different preparation approaches, cell fractionation
      followed by one-dimensional gel separation and in-solution digestion of total
      cell lysate combined with isoelectric focusing, and found comparable proteome
      coverage with no apparent bias for any functional protein classes for either
      approach. Bioinformatics analysis of the ES cell proteome revealed a broad
      distribution of cellular functions with overrepresentation of proteins involved
      in proliferation. We compared the proteome with a recently published map of
      chromatin states of promoters in ES cells and found excellent correlation between
      protein expression and the presence of active and repressive chromatin marks.

PMID- 18045803
TI  - Proteomics analysis of cells in whole saliva from oral cancer patients via value
      added three-dimensional peptide fractionation and tandem mass spectrometry.
AB  - Whole human saliva possesses tremendous potential in clinical diagnostics,
      particularly for conditions within the oral cavity such as oral cancer. Although
      many have studied the soluble fraction of whole saliva, few have taken advantage
      of the diagnostic potential of the cells present in saliva, and none have taken
      advantage of proteomics capabilities for their study. We report on a novel
      proteomics method with which we characterized for the first time cells contained
      in whole saliva from patients diagnosed with oral squamous cell carcinoma. Our
      method uses three dimensions of peptide fractionation, combining the following
      steps: preparative IEF using free flow electrophoresis, strong cation exchange
      step gradient chromatography, and microcapillary reverse-phase liquid
      chromatography. We determined that the whole saliva samples contained enough
      cells, mostly exfoliated epithelial cells, providing adequate amounts of total
      protein for proteomics analysis. From a mixture of four oral cancer patient
      samples, the analysis resulted in a catalogue of over 1000 human proteins, each
      identified from at least two peptides, including numerous proteins with a role in
      oral squamous cell carcinoma signaling and tumorigenesis pathways. Additionally
      proteins from over 30 different bacteria were identified, some of which
      putatively contribute to cancer development. The combination of preparative IEF
      followed by strong cation exchange chromatography effectively fractionated the
      complex peptide mixtures despite the closely related physiochemical peptide
      properties of these separations (pI and solution phase charge, respectively).
      Furthermore compared with our two-step method combining preparative IEF and
      reverse-phase liquid chromatography, our three-step method identified
      significantly more cellular proteins while retaining higher confidence protein
      identification enabled by peptide pI information gained through IEF. Thus, for
      detecting salivary markers of oral cancer and possibly other conditions of the
      oral cavity, the results confirm both the potential of analyzing the cells in
      whole saliva and doing so with our proteomics method.

PMID- 18045805
TI  - Quantitative evaluations of a high-voltage multiscan CCD camera.
AB  - Electron detection characteristics such as modulation transfer function (MTF),
      detection quantum efficiency (DQE), dynamic range, linearity, average gain, and
      uniformity of a high-voltage multiscan CCD (HV-MSC, 1K x 1K pixels) camera were
      evaluated. This camera was used as a major recording medium in a high-voltage
      electron microscope (HVEM) installed at the Korea Basic Science Institute (KBSI).
      In spite of the high energy of the incident electrons, the overall properties of
      the HV-MSC camera were comparable to other CCD cameras for a low-voltage electron
      microscope (LVEM). In order to take full advantages of the properties of the HV
      MSC camera for atomic resolution electron microscopy, we discuss optimal
      experimental conditions based on the detection properties.

PMID- 18045804
TI  - Repair of DNA double-strand breaks within the (GAA*TTC)n sequence results in
      frequent deletion of the triplet-repeat sequence.
AB  - Friedreich ataxia is caused by an expanded (GAA*TTC)n sequence, which is unstable
      during intergenerational transmission and in most patient tissues, where it
      frequently undergoes large deletions. We investigated the effect of DSB repair on
      instability of the (GAA*TTC)n sequence. Linear plasmids were transformed into
      Escherichia coli so that each colony represented an individual DSB repair event.
      Repair of a DSB within the repeat resulted in a dramatic increase in deletions
      compared with circular templates, but DSB repair outside the repeat tract did not
      affect instability. Repair-mediated deletions were independent of the orientation
      and length of the repeat, the location of the break within the repeat or the RecA
      status of the strain. Repair at the center of the repeat resulted in deletion of
      approximately half of the repeat tract, and repair at an off-center location
      produced deletions that were equivalent in length to the shorter of the two
      repeats flanking the DSB. This is consistent with a single-strand annealing
      mechanism of DSB repair, and implicates erroneous DSB repair as a mechanism for
      genetic instability of the (GAA*TTC)n sequence. Our data contrast significantly
      with DSB repair within (CTG*CAG)n repeats, indicating that repair-mediated
      instability is dependent on the sequence of the triplet repeat.

PMID- 18045806
TI  - Primary prevention of type-2 diabetes and heart disease: action research in
      secondary schools serving an ethnically diverse UK population.
AB  - BACKGROUND: Escalating rates of childhood obesity are likely to have an impact on
      the prevalence of coronary heart disease and type-2 diabetes. We aimed to
      identify barriers to healthy lifestyles and evaluate the effectiveness of an
      action research approach to lifestyle modification in secondary schools. METHODS:
      An action research partnership between schools and university researchers
      involved pupils aged 11-15 in five inner-city secondary schools serving a
      predominantly South Asian population in Leicester, UK. Data collection included
      baseline and follow-up diet and physical activity questionnaires. Focus groups
      and observational visits were used to identify barriers, assist with developing
      tailored interventions and review the impact of the study. RESULTS: Working with
      secondary schools presented challenges but a useful partnership was sustained.
      Qualitative feedback suggested that this had raised awareness of healthy
      lifestyle issues in participating schools. Barriers in pupils included low
      prioritization of health when making lifestyle choices. Sub-optimal diet and
      activity habits were identified at baseline. Overall, these persisted at follow
      up, although some limited positive changes were identified. CONCLUSIONS: Using
      action research methods in this context is challenging but can facilitate useful
      data collection and may have a modest impact on lifestyle behaviours.

PMID- 18045807
TI  - Progressive multifocal leucoencephalopathy in a patient with systemic lupus
      erythematosus treated with rituximab.

PMID- 18045808
TI  - Recent insights in the pharmacological actions of methotrexate in the treatment
      of rheumatoid arthritis.
AB  - This review presents recent data supporting the methotrexate (MTX) mechanisms of
      action, which are likely to account for its anti-proliferative and
      immunosuppressive effects in rheumatoid arthritis (RA). The effects of MTX in
      vivo may be mediated by reducing cell proliferation, increasing the rate of
      apoptosis of T cells, increasing endogenous adenosine release, altering the
      expression of cellular adhesion molecules, influencing production of cytokines,
      humoral responses and bone formation. Several reports indicate that the effects
      of MTX are influenced by genetic variants, specific dynamic processes and micro
      environmental elements such as nucleotide deprivation or glutathione levels. The
      challenge for the future will be linking biological and genetic markers relevant
      to the response to MTX in RA.

PMID- 18045809
TI  - Non-invasive quantification of popliteal cyst volumes by three-dimensional
      ultrasonography.

PMID- 18045810
TI  - Rheumatoid arthritis, cardiovascular disease and physical exercise: a systematic
      review.
AB  - This systematic review investigates the effectiveness of exercise interventions
      in improving disease-related characteristics in patients with rheumatoid
      arthritis (RA). It also provides suggestions for exercise programmes suitable for
      improving the cardiovascular profile of RA patients and proposes areas for future
      research in the field. Six databases (Medline, Cochrane Library, CINAHL, Google
      Scholar, EMBASE and PEDro) were searched to identify publications from 1974 to
      December 2006 regarding RA and exercise interventions. The quality of the studies
      included was determined by using the Jadad scale. Initial searches identified
      1342 articles from which 40 met the inclusion criteria. No studies were found
      investigating exercise interventions in relation to cardiovascular disease in RA.
      There is strong evidence suggesting that exercise from low to high intensity of
      various modes is effective in improving disease-related characteristics and
      functional ability in RA patients. Future studies are required to investigate the
      effects of exercise in improving the cardiovascular status of this patient
      population.

PMID- 18045811
TI  - MRI of rheumatoid arthritis image quantitation for the assessment of disease
      activity, progression and response to therapy.
AB  - Magnetic resonance imaging (MRI) allows the direct visualization of many bone and
      soft tissue changes in rheumatoid arthritis. Synovitis volume, bone marrow oedema
      and bone erosions are suitable for serial measurement. The outcome measures in
      rheumatoid arthritis clinical trials (OMERACT) rheumatoid arthritis magnetic
      resonance imaging (RAMRIS) system is designed to allow straightforward,
      reproducible scoring of all these features. Alternatively, synovial volumes may
      be directly and quickly measured using semi-automated techniques. There is the
      potential for similar systems for measuring erosions. Dynamic contrast enhanced
      MRI depends on the rate of enhancement of the synovium after intravenous contrast
      agent. Measurements depend on the underlying physiology of the inflamed synovium,
      in particular the vascularity and capillary permeability which are expected to
      closely mirror inflammatory activity in the joint. Measurements from MRI have
      been shown to correlate with clinical, laboratory, imaging and histological
      measures of inflammation, predict erosive progression and respond rapidly to
      various types of treatment. They are, therefore, expected to be good measures of
      disease activity, progression and response to therapy.

PMID- 18045812
TI  - Function of jasmonate in response and tolerance of Arabidopsis to thrip feeding.
AB  - We analyzed the interaction between Arabidopsis and western flower thrips
      (Frankliniella occidentalis), which are one of the most serious insect pests of
      cultivated plants. We focused on the function of the immunity-related plant
      hormones jasmonate (JA), ethylene (ET) and salicylic acid (SA) in the plant's
      response to thrip feeding. Expression of the marker genes for each hormone
      response was induced by thrip feeding in wild-type (WT) plants. Further analyses
      in the hormone-related mutants coi1-1 (JA insensitive), ein2-1 and ein3-1 (ET
      insensitive) and eds16-1 (SA deficient) suggested the importance of these
      hormones in the plant response to feeding. Comparative transcriptome analyses
      suggested a strong relationship between thrip feeding and JA treatment, but not
      ET or SA treatment. The JA content of WT plants was significantly increased after
      thrip feeding. Moreover, coi1-1, but not ein2-1, showed lower feeding tolerance
      against thrips than the WT. Application of JA to WT plants before thrip feeding
      enhanced the plants' feeding tolerance. JA modulates several defense responses in
      cooperation with ET, but application of the ET precursor 1-aminocyclopropane
      carboxylic acid had a marked negative effect on feeding tolerance. Our results
      indicate that JA plays an important role in Arabidopsis in terms of response to,
      and tolerance against, thrip feeding.

PMID- 18045813
TI  - Ultrastructural characterization of exine development of the transient defective
      exine 1 mutant suggests the existence of a factor involved in constructing
      reticulate exine architecture from sporopollenin aggregates.
AB  - A male-sterile mutant of Arabidopsis thaliana, in which filament elongation was
      defective although pollen fertility was normal, was isolated by means of T-DNA
      tagging. Transmission electron microscopy (TEM) analysis revealed that primexine
      synthesis and probacula formation, which are thought to be the initial steps of
      exine formation, were defective, and that globular sporopollenin aggregation was
      randomly deposited onto the microspore at the early uninucleate microspore stage.
      Sporopollenin aggregation, which failed to anchor to the microspore plasma
      membrane, was deposited on the locule wall and in the locule at the uninucleate
      microspore stage. However, visually normal exine with a basic reticulate
      structure was observed at the middle uninucleate microspore stage, indicating
      that the exine formation was restored in the mutant. Thus, the mutant was
      designated transient defective exine 1 (tde1). These results indicated that tde1
      mutation affects the initial process of the exine formation, but does not impair
      any critical processes. Our results also suggest the existence of a certain
      factor responsible for exine patterning in A. thaliana. The TDE1 gene was found
      to be identical to the DE-ETIOLATED 2 gene known to be involved in
      brassinosteroid (BR) biosynthesis, and the tde1 probacula-defective phenotypes
      were recovered in the presence of BR application. These results suggest that BRs
      control the rate or efficiency of initial process of exine pattern formation.

PMID- 18045814
TI  - Impact of high temperatures on hospital admissions: comparative analysis with
      previous studies about mortality (Madrid).
AB  - BACKGROUND: Heat wave prevention plans are traditionally implemented according to
      a temperature limit above which mortality begins to rise. Although these
      prevention plans are obviously designed to avoid deaths, it is also necessary to
      establish the impact of extreme temperatures on hospital admissions in order to
      put hospital alert plans into action for dealing with people affected by heat
      wave victims. METHODS: We used data on daily emergency admissions between May and
      September, from 1995 to 2000, in the Hospital General Universitario Gregorio
      Maranon in Madrid. The causes for admission were considered as 'organic'
      (International Classification of Diseases, ICD-9: 1-799), circulatory (ICD-9: 390
      459) and respiratory (ICD-9: 460-519). We stratified them according to the
      following age groups: all ages, from 0 to 10, 18 to 44, 45 to 64, 65 to 74 and
      above 75 years. The methodology used was Autorregresive Integrated Moving Average
      (ARIMA) modelling, including variables related to atmospheric pollution,
      seasonality and trends. RESULTS: The results show that the temperature above
      which hospital admissions soar coincides with the temperature limit above which
      mortality sharply rises, which, in turn, coincides with percentile 95 of the
      maximum daily temperature series for summer months. The pattern of hospital
      admissions is completely different from that of mortality. The rise in hospital
      admissions due to all causes and age groups is clearly smaller than that detected
      for mortality. DISCUSSION: These results suggest that people die rapidly from
      circulatory diseases before they can be admitted to hospital. This datum is vital
      with regard to implementing prevention plans prior to the arrival of the heat
      wave, if they are to effectively reduce mortality.

PMID- 18045815
TI  - Insulin action on glucose and protein metabolism during L-carnitine
      supplementation in maintenance haemodialysis patients.
AB  - BACKGROUND: Impaired protein anabolism and insulin resistance are characteristic
      features of maintenance haemodialysis patients. We have used a randomised,
      matched-paired, double-blind, placebo-controlled experimental design to determine
      the capability of intravenous L-carnitine supplementation to modify insulin
      resistance and protein catabolism in non-diabetic patients with end-stage renal
      disease (ESRD) undergoing chronic haemodialysis treatment. METHODS: L-carnitine
      (20 mg x kg(-1)) (n = 9) or placebo (n = 10) were given intravenously at the end
      of seven consecutive dialysis sessions. Whole-body protein and glucose metabolism
      were assessed on interdialytic days by the L[1-(13)C]leucine and the [2,2
      (2)H(2)]glucose kinetic models in the postabsorptive state and during euglicemic
      hyperinsulinemic clamp studies at baseline and at the end of the treatment
      period. RESULTS: L-carnitine supplementation was associated with lower (P < 0.05)
      rates of leucine oxidation (-11 +/- 12%) and appearance from proteolysis (-6 +/-
      2%) during the clamp studies than after placebo supplementation. The rates of
      glucose appearance in the postabsorptive state did not change significantly in
      the patients receiving L-carnitine treatment. Insulin-mediated glucose
      disappearance was improved by L-carnitine only in those patients (n = 5) (+18 +/-
      3%, P < 0.05 vs placebo group, n = 5) with greater baseline insulin resistance,
      selected according to the median value of insulin sensitivity before treatment.
      CONCLUSIONS: L-carnitine supplementation was associated with protein-sparing
      effects in maintenance haemodialysis patients during hyperinsulinemia.

PMID- 18045816
TI  - Transforming growth factor-beta1 decreases epithelial sodium channel
      functionality in renal collecting duct cells via a Smad4-dependent pathway.
AB  - BACKGROUND: Transformation growth factor-beta1 (TGF-beta1) inhibits
      transepithelial sodium transport and suppresses the epithelial sodium channel
      (ENaC) in many different types of epithelial cells; however, the molecular
      mechanism of this effect in the kidney is still not clear. The aim of this study
      was to examine the regulation of transepithelial sodium transport by TGF-beta1 in
      renal cells. METHODS: We derived stable mouse cortical collecting duct cell lines
      that overexpressed Smad4 or N-termianl truncated Smad4, and studied the effects
      of TGF-beta1 on them. The equivalent electrical current (I(eq)) was taken as
      representing transepithelial current and the amiloride sensitive short circuit
      current (AmsIsc) as representing the ENaC activity. We used real-time PCR to
      quantify the expression of ENaC and measurement of the luciferase activity of
      cells transiently transfected with a mouse alpha-ENaC promoter to assess the
      alpha-ENaC promoter activity. Result. The administration of TGF-beta1 decreased
      I(eq), mainly as a result of the decrease of AmsIsc, and it correlated with
      inhibition of the alpha-ENaC mRNA expression. The overexpression of Smad4 led to
      a decrease in AmsIsc, alpha-ENaC mRNA and alpha-ENaC promoter activity, but the
      overexpression of the N-terminal truncated Smad4 did not induce these changes.
      The TGF-beta1-induced reduction of AmsIsc was alleviated in the N-terminal
      truncated Smad4-overexpressed cells. CONCLUSION: It appears that the N-terminus
      region of Smad4 is indispensable in Smad4-mediated inhibition of the
      transepithelial sodium transport. TGF-beta1 may decrease the ENaC functionality
      via a Smad4-dependent pathway.

PMID- 18045817
TI  - Unusual saprophytic bacterial infection as emerging opportunistic pathogens in
      kidney transplantation.

PMID- 18045818
TI  - A novel variant apolipoprotein E Okayama in a patient with lipoprotein
      glomerulopathy.

PMID- 18045819
TI  - Haemodiafiltration: promise for the future?

PMID- 18045820
TI  - A murine model of site-specific renal microvascular endothelial injury and
      thrombotic microangiopathy.
AB  - Despite the importance of endothelial injury and healing for primary and
      secondary renal disease and the availability of genetically engineered mouse
      models, to date no generally applicable murine disease model with site-specific
      renal endothelial injury has been established. We induced specific microvascular
      renal injury via selective renal arterial perfusion of the lectin concanavalin A
      (Con A) followed by sheep anti-concanavalin A and harvested tissues after 4 h, 24
      h, days 3 and 7. Compared to control kidneys, histological evaluation
      demonstrated endothelial cell injury with subsequent complement, and platelet
      activation and thrombosis by light and electron microscopy. Mouse kidneys showed
      histologic evidence of severe glomerular and peritubular microvascular thrombosis
      with acute tubular necrosis, proteinuria, increased BUN and presence of
      schistocytes. Initial cell death of intrinsic renal cells resulted in a decrease
      of the glomerular cell count by 50% after 4 h followed by a proliferative
      response of glomerular (day 3, P < 0.05), interstitial (day 3, P < 0.05) and
      tubular cells leading to increased total glomerular cell count by day 7. This
      study establishes the Con A anti-Con A model as specific endothelial injury model
      in the mouse kidney providing a novel tool for investigating endothelial injury
      and repair mechanisms as well as elucidating the role of platelets in genetically
      engineered mice.

PMID- 18045821
TI  - Calcium and potassium changes during haemodialysis alter ventricular
      repolarization duration: in vivo and in silico analysis.
AB  - BACKGROUND: Alterations of ventricular repolarization duration, as measured by
      the QT interval, are frequently observed in haemodialysis (HD) patients. The
      nature and the sign of these changes are not yet fully understood. METHODS:
      Different dialysate K(+) and Ca(2+) levels, leading to different end-HD plasma
      concentrations in the patient, have been tested in the present study in terms of
      their impact on QTc. A model of the human cardiomyocyte action potential (AP) has
      been used to assess in silico whether the changes in Ca(2+) and K(+) were able to
      justify at the cellular level the observed alterations of QTc. RESULTS: QTc was
      prolonged in HDs with low (1.25 mM) versus high (2 mM) Ca(2+) (424 +/- 33 versus
      400 +/- 28 ms, P < 0.05) and in HDs with low (2 mM) versus high (3 mM) K(+) (420
      +/- 35 versus 399 +/- 36 ms, P < 0.05). These alterations were confirmed at the
      cellular level by computational analysis showing prolongation of ventricular AP
      at low K(+) and low Ca(2+) at the same extent of the measured QTc variations.
      Numerical simulation predicted a critically long AP (and QT) when considering low
      K(+) and Ca(2+) simultaneously, suggesting the concurrent lowering of Ca(2+) and
      K(+) as a potential arrhythmogenic factor. CONCLUSIONS: Numerical simulations of
      the ventricular AP may be useful to quantitatively predict the complex dependence
      of AP duration on simultaneous changes in Ca(2+) and K(+). Moreover, Ca(2+)
      content in the dialysate should be designed not to critically lower serum Ca(2+),
      especially in sessions at risk of end-dialysis hypokalaemia.

PMID- 18045822
TI  - Anaemia and congestive heart failure early post-renal transplantation.
AB  - BACKGROUND: Anaemia is common following renal transplantation and is associated
      with the development of congestive heart failure (CHF). However the prevalence of
      anaemia in the first year following transplantation and the association between
      anaemia occurring early and the development of CHF have been understudied.
      METHODS: In this study, 132 incident patients undergoing tacrolimus and
      mycophenolate mofetil-based renal transplantation were studied for the prevalence
      of, and risk factors for, anaemia and CHF in the early period post
      transplantation. RESULTS: Anaemia occurred in 94.5% and 53.1% of patients at 1
      week and 12 months, respectively, and was associated with allograft dysfunction,
      hypoalbuminaemia, higher mycophenolic acid (MPA) levels, bacterial infection and
      hypoalbuminaemia. The association with hypoalbuminaemia may reflect the presence
      of chronic inflammation post-transplantation. Of patients displaying haemoglobin
      <11 g/dl, 41.1% and 29.4% were treated with erythropoiesis stimulating agents
      (ESAs) at 1 and 12 months respectively. CHF developed in 26 patients beyond 1
      month post-transplantation, with echocardiographic left ventricular systolic
      function preserved in all but one. CHF was associated with anaemia and lower
      haemoglobin, allograft dysfunction, duration of dialysis and left ventricular
      hypertrophy on echocardiography prior to transplantation, suggesting the
      aetiology of CHF may involve the interplay of diastolic cardiac dysfunction, pre
      load mismatch and after-load mismatch. CONCLUSIONS: Modification of risk factors
      may improve anaemia management post transplantation. Reducing the prevalence of
      anaemia may in turn reduce the incidence of CHF-these observations support the
      need for clinical trials to determine how anaemia management may impact CHF
      incidence.

PMID- 18045823
TI  - Th17 cells: a third subset of CD4+ T effector cells involved in organ-specific
      autoimmunity.

PMID- 18045824
TI  - Pre-transplant predictors of cerebrovascular events after kidney transplantation.
AB  - BACKGROUND: We evaluated cerebrovascular events (CVE) after kidney
      transplantation (KTx) and sought to identify pre-transplant predictors of
      transient ischaemic attacks (TIA) and strokes post-transplantation. METHODS: A
      total of 1617 consecutive kidney and 16 kidney-pancreas recipients transplanted
      between 1995 and 2005 were analysed in this retrospective single-centre study.
      Risk factors for CVE, e.g. recipient and donor age and gender, diagnosis of
      chronic kidney disease, end-stage renal disease (ESRD) duration, histories of
      hypertension, hyperlipidaemia, smoking, atrial fibrillation (AF), diabetes
      mellitus (DM), ischaemic heart, peripheral- and cerebro-vascular disease, as well
      as pre-transplant myocardial infarction or CVE (i.e. TIA/strokes) were analysed.
      Furthermore, the predictive value of pre-transplant screening tests, i.e.
      echocardiography (n = 1184) and carotid ultrasound (n = 922), was investigated.
      RESULTS: During a median follow-up of 4 years, 64 CVE (54 strokes and 10 TIA)
      were observed. Nineteen (5.1%) of 373 deceased patients died from fatal stroke.
      Recipient age, history of AF and hyperlipidaemia (P = 0.00, respectively),
      reduced left ventricular function (LVF) (P = 0.01) and the degree of stenosis by
      carotid ultrasound (P = 0.002), duration of ESRD (P = 0.03) and interstitial
      nephritis as renal disease cause (P = 0.04) evolved as predictors of TIA/stroke
      post-transplant in univariate analysis. In multivariable analysis, AF (P = 0.001)
      and DM (P = 0.037) were significant predictors for post-transplant CVE.
      CONCLUSIONS: AF and DM are independent predictors of CVE after KTx. Beyond their
      general ability to detect sev- erely comorbid patients, pre-transplant screening
      tests (e.g. carotid ultrasound or echocardiography) were not able to identify
      renal transplant candidates at risk for CVE after transplantation.

PMID- 18045826
TI  - Effects of cinacalcet on gastrointestinal hormone release in patients with
      secondary hyperparathyroidism undergoing dialysis.
AB  - Objective. Our aim has been evaluating the influence of an acute dose of
      cinacalcet on the gastrointestinal hormonal responses to a test meal in uraemic
      patients with secondary hyperparathyroidism undergoing peritoneal dialysis (PD)
      or haemodialysis (HD). METHODS: Twenty patients (11 PD, 9 HD) on cinacalcet
      treatment (30-120 mg/day) were studied. Twelve patients (1 PD, 11 HD) who never
      received cinacalcet were studied as control group. Each patient received a test
      meal with blood samples at 0, 2 and 4 h. At 0 time, patients in the cinacalcet
      group received their usual oral dose of this calcimimetic. Plasma concentrations
      of intact parathyroid hormone (PTH), vasoactive intestinal peptide (VIP),
      ghrelin, substance P, serotonin, cholecystokinin (CCK) and gastrin were
      quantified at 0, 2 and 4 h. RESULTS: No significant differences in baseline
      concentrations of serum VIP, ghrelin, substance P, serotonine, CCK and gastrin
      were found between controls and cinacalcet-treated patients. In comparison with
      the control group, cinacalcet administration was followed by a significant
      decrease in VIP concentration at 4 h and a significant increase in substance P at
      4 h. However, the areas under the curves of all studied gut hormones were similar
      in both groups. CONCLUSION: An acute dose of cinacalcet exerts minimal influence
      on gut hormone responses to a mixed meal in dialysis patients on chronic therapy
      with this drug. The small but significant differences between control subjects
      and patients on cinacalcet in VIP and substance P levels at 4 h should be
      investigated in symptomatic patients.

PMID- 18045825
TI  - The prognosis and pathogenesis of severe lupus glomerulonephritis.
AB  - BACKGROUND: The International Society of Nephrology/ Renal Pathology Society
      classification (ISN/RPS) of lupus glomerulonephritis (GN) divides diffuse GN
      (>/=50% involvement) into diffuse segmental (IV-S) and diffuse global GN (IV-G).
      This division tests whether the pathogenesis and clinical outcomes are the same
      as when similar patients are classified using the World Health Organization (WHO)
      classification into severe segmental (WHO III >/=50%) and diffuse global (WHO-IV)
      GN. METHODS: Thirty-nine renal biopsies with WHO class IV and 44 with WHO III >/=
      50% were reclassified using the ISN/RPS and were correlated with pathogenesis and
      outcome. RESULTS: There were 22 biopsies with ISN/RPS class IV-S. ISN/RPS class
      IV-G comprises two morphologically discrete classes of renal biopsies: 39
      biopsies originally classified as WHO class IV (WHO-IV) and 22 that switched from
      WHO III >/=50% to ISN/RPS class IV-G (IV-Q). We will analyze IV-S, IV-Q and WHO
      IV separately. WHO-IV had significantly more immune aggregate deposition than IV
      S and IV-Q. WHO-IV had lower serum complements C3 (P = 0.05) and C4 (P = 0.05)
      than patients with IV-Q. Patients with WHO-IV had more remissions (56%) than IV-Q
      (23%) (P = 0.01), and stable renal function at the last follow-up was less
      frequent in patients with IV-Q (18%) than IV-S (50%, P = 0.05) and WHO-IV (62%, P
      = 0.001). Renal survival and renal survival without end-stage renal disease were
      different when the patients were diagnosed as WHO classes III >/=50% and IV, but
      the outcomes for ISN/RPS class IV-S and IV-G (WHO-IV plus IV-Q) were not
      different. CONCLUSIONS: WHO III >/=50% and WHO-IV lupus GN are not congruent with
      ISN/RPS IV-S and IV-G. The ISN/RPS minimizes pathological and outcome differences
      between classes IV-S and IV-G which results in the loss of informational content
      from the renal biopsies. ISN/RPS does not detect pathogenetic or clinical
      differences among patients with severe lupus GN.

PMID- 18045827
TI  - Association of functional haem oxygenase-1 gene promoter polymorphism with
      polycystic kidney disease and IgA nephropathy.
AB  - BACKGROUND: Haem oxygenase-1 (HO-1) is a cytoprotective molecule that is reported
      to have a protective role in a variety of experimental models of renal injury. A
      functional dinucleotide repeat (GT)(n) polymorphism, within the HO-1 promoter,
      regulates HO-1 gene expression; a short number of repeats (S-allele <25)
      increases transcription. We report the first assessment of the role of this HO-1
      gene promoter polymorphism in chronic kidney disease due to autosomal dominant
      polycystic kidney disease (ADPKD) and IgA nephropathy (IgAN). METHODS: The DNA
      from 160 patients (99% Caucasian) on renal replacement therapy (RRT) was
      genotyped. The primary renal disease was ADPKD in 100 patients and biopsy-proven
      IgAN in 60 patients. RESULTS: Overall, the mean age at commencement of RRT was
      not significantly different between patients with and without an S-allele (44.1
      years versus 45.0 years, P = 0.64). In patients with ADPKD, the age at
      commencement of RRT was comparable regardless of the HO-1 genotype (47.7 years
      versus 46.7 years, P = 0.59). The same was true in patients with IgAN (38.3 years
      versus 42.2 years, P = 0.28). CONCLUSION: This suggests that the functional HO-1
      promoter polymorphism does not influence renal survival in CKD due to ADPKD or
      IgAN.

PMID- 18045828
TI  - Is PTH a risk factor for cardiovascular calcifications in haemodialysis?

PMID- 18045829
TI  - Extended duration of brachially inserted intra-aortic balloon pump for myocardial
      protection in two patients undergoing urgent coronary artery bypass grafting.
AB  - Intra-aortic balloon pump (IABP) provides myocardial protection for patients who
      are at risk of myocardial injury during cardiac surgery. The haemodynamic support
      is crucial in patients with significant and critical coronary artery disease
      undergoing revascularisation procedures. Traditionally, the femoral arterial
      access is the preferred route for IABP insertion. This is, however, not always
      feasible especially in patients with concomitant occlusive peripheral vascular
      disease. The trans-brachial route can be used as an alternative for percutaneous
      insertion of the IABP. We report the technique for left trans-brachial insertion
      of an IABP, and illustrate our experience with two patients requiring urgent
      coronary artery bypass grafting (CABG) and for whom the IABP duration was over 50
      h.

PMID- 18045830
TI  - Successful treatment of an aggressive non-Hodgkin's lymphoma associated with
      acute respiratory insufficiency using extracorporeal membrane oxygenation.
AB  - Non-Hodgkin's lymphoma initially presenting as a solid huge mediastinal mass does
      not frequently occur. Although nowadays many patients with high-grade
      (aggressive) malignant lymphoma can be cured using a combination of immuno- and
      chemotherapy, rapid progression and acute complications caused by the tumor mass
      itself may necessitate additional invasive treatment. We report a case of
      successful extracorporeal membrane oxygenation treatment in a 43-year-old woman
      with acute respiratory insufficiency due to a huge mediastinal non-Hodgkin's
      tumor.

PMID- 18045831
TI  - Medium-term outcome of different surgical methods to cure atrial fibrillation: is
      less worse?
AB  - Different lesion sets and ablation techniques have been performed. We compared
      these outcomes in search of the best method. We performed a retrospective
      analysis of patients who have undergone AF surgery different from the maze III.
      The surgical lesion sets were pulmonary vein isolation (PVI) alone, left atrial
      maze (LAM) and bi-atrial maze (BAM) and were made with different ablation
      techniques. During surgery one patient died due to bleeding of a pulmonary vein.
      The number of patients in the PVI-, LAM-, BAM-groups was 12, 28 and 26,
      respectively, with freedom from AF at latest follow-up [22.0+/-15.6 (3.1-81.2)
      months] of 33%, 59% and 60%, respectively. Atrial flutter occurred less in the
      BAM-group (4%) than in the left-sided procedures (15.4%) (P=0.231). Multivariate
      analysis demonstrated a higher recurrence of AF for PVI alone (OR 4.42, CL 0.95
      20.6, P=0.0583) and a lower recurrence for the 'cut-and-sew' technique (OR 0.13,
      CL 0.030-0.60, P=0.0084). Left- and bi-atrial maze procedures are equally
      effective in the suppression of AF, whereas omission of right-sided lesions
      results in a higher prevalence of atrial flutter. The 'cut-and-sew' technique is
      superior in terms of freedom from AF compared to bipolar and unipolar
      radiofrequency.

PMID- 18045832
TI  - Modeling the adaptive immune system: predictions and simulations.
AB  - MOTIVATION: Immunological bioinformatics methods are applicable to a broad range
      of scientific areas. The specifics of how and where they might be implemented
      have recently been reviewed in the literature. However, the background and
      concerns for selecting between the different available methods have so far not
      been adequately covered. SUMMARY: Before using predictions systems, it is
      necessary to not only understand how the methods are constructed but also their
      strength and limitations. The prediction systems in humoral epitope discovery are
      still in their infancy, but have reached a reasonable level of predictive
      strength. In cellular immunology, MHC class I binding predictions are now very
      strong and cover most of the known HLA specificities. These systems work well for
      epitope discovery, and predictions of the MHC class I pathway have been further
      improved by integration with state-of-the-art prediction tools for proteasomal
      cleavage and TAP binding. By comparison, class II MHC binding predictions have
      not developed to a comparable accuracy level, but new tools have emerged that
      deliver significantly improved predictions not only in terms of accuracy, but
      also in MHC specificity coverage. Simulation systems and mathematical modeling
      are also now beginning to reach a level where these methods will be able to
      answer more complex immunological questions.

PMID- 18045833
TI  - In vivo regulation of AT1a receptor-mediated intracellular uptake of [125I]Val5
      ANG II in the kidneys and adrenals of AT1a receptor-deficient mice.
AB  - Using type 1a angiotensin receptor (AT1a) receptor-deficient (Agtr1a-/-) mice and
      in vivo autoradiography, we tested the hypothesis that intracellular uptake of
      ANG II in the kidney and adrenal glands is primarily mediated by AT1a receptors
      and that the response is regulated by prevailing endogenous ANG II. After
      pretreatment of wild-type (Agtr1a+/+) and Agtr1a-/- mice (n = 6-9 each group)
      with or without captopril (25 mg.kg(-1).day(-1)) or losartan (10 mg.kg(-1).day(
      1)) for 2 wk, [125I]Val5-ANG II was infused for 60 min. Intracellular uptake of
      [125I]Val5-ANG II was determined by quantitative in vivo autoradiography after
      washout of circulating [125I]Val5-ANG II. Basal intracellular ANG II levels were
      65% lower in the kidney (P < 0.001), but plasma ANG II levels were threefold
      higher, in Agtr1a-/- than wild-type mice (P < 0.01). Although plasma [125I]Val5
      ANG II levels were similar, urinary excretion of [125I]Val5-ANG II was fourfold
      higher in Agtr1a-/- mice (P < 0.001). By contrast, intracellular [125I]Val5-ANG
      II levels were approximately 80% lower in the kidney and adrenal glands of Agtr1a
      /- mice (P < 0.01). Captopril decreased endogenous plasma and renal ANG II levels
      (P < 0.01) but increased intracellular uptake of [125I]Val5-ANG II in the kidney
      and adrenal glands of wild-type and Agtr1a-/- mice (P < 0.01). Losartan largely
      blocked renal and adrenal uptake of [125I]Val5-ANG II in wild-type and Agtr1a-/-
      mice. Thus 80% of intracellular ANG II uptake in the kidney and adrenal glands is
      mediated by AT1a receptors, whereas AT1b receptor- and other non-receptor
      mediated mechanisms account for 20% of the response. Our results suggest that
      AT1a receptor-mediated uptake of extracellular ANG II may play a physiological
      role in the kidney and adrenal glands.

PMID- 18045834
TI  - The small GTPase Rac-1 is a regulator of mesangial cell morphology and
      thrombospondin-1 expression.
AB  - Thrombospondin-1 (TSP-1), which is synthesized by mesangial cells, is known for
      its anti-angiogenic activity and its ability to activate latent TGF-beta. TSP-1
      is upregulated in renal diseases associated with tissue remodeling. Therefore, we
      hypothesized that the expression of TSP-1 might be modulated by changes in cell
      morphology involving proteins of the Rho family. Spreading of mesangial cells
      after detachment and reseeding was characterized by the formation of lamellipodia
      and focal adhesions, pointing toward a Rac-1-mediated rearrangement of actin
      structures. Clustering of focal adhesion proteins was also observed in a model
      system of nocodazole-induced disruption of microtubules. These morphological
      alterations were impeded by pharmacological inhibition of Src family kinases, of
      the small GTPase Rac-1, or by downregulation of Rac-1 by siRNA. Upon cell
      spreading, TSP-1 was upregulated in the absence and much more prominently in the
      presence of serum, but also after nocodazole treatment. TSP-1 upregulation was
      controlled by activation of Src family kinases, ERK 1/2 and Rac-1, whereas
      activation of RhoA-ROCK signaling was not linked to TSP-1 induction. We thus
      provide evidence that TSP-1 expression is induced by common signaling pathways,
      which are activated by morphological alterations of renal mesangial cells or by
      soluble factors as contained in serum, and these pathways include Src family
      kinases, ERK 1/2 and Rac-1. Our data suggest that tissue remodeling activates
      gene expression of pathophysiologically relevant proteins such as TSP-1.

PMID- 18045835
TI  - A stem-loop structure in the wingless transcript defines a consensus motif for
      apical RNA transport.
AB  - Although the subcellular localization of mRNA transcripts is a well-established
      mechanism for controlling protein localization, the basis for the recognition of
      mRNA localization elements is only now emerging. For example, although
      localization elements have been defined for many mRNAs that localize to apical
      cytoplasm in Drosophila embryos, no unifying properties have been identified
      within these elements. In this study, we identify and characterize an apical
      localization element in the 3'UTR of the Drosophila wingless mRNA. We show that
      this element, referred to as WLE3, is both necessary and sufficient for apical
      RNA transport. Full, unrestricted activity, however, requires the presence of one
      of several downstream potentiating elements. Comparison of WLE3 sequences within
      the Drosophila genus, and their predicted secondary structures, defines a highly
      conserved stem-loop structure. Despite these high levels of sequence and
      predicted structure conservation, however, mutagenesis shows significant leeway
      for both sequence and structure variation in the predicted stem-loop.
      Importantly, the features that emerge as crucial include an accessible distal
      helix sequence motif, which is also found in the predicted structures of other
      apical localization elements.

PMID- 18045836
TI  - Sisyphus, the Drosophila myosin XV homolog, traffics within filopodia
      transporting key sensory and adhesion cargos.
AB  - Unconventional myosin proteins of the MyTH-FERM superclass are involved in
      intrafilopodial trafficking, are thought to be mediators of membrane-cytoskeleton
      interactions, and are linked to several forms of deafness in mammals. Here we
      show that the Drosophila myosin XV homolog, Sisyphus, is expressed at high levels
      in leading edge cells and their cellular protrusions during the morphogenetic
      process of dorsal closure. Sisyphus is required for the correct alignment of
      cells on opposing sides of the fusing epithelial sheets, as well as for adhesion
      of the cells during the final zippering/fusion phase. We have identified several
      putative Sisyphus cargos, including DE-cadherin (also known as Shotgun) and the
      microtubule-linked proteins Katanin-60, EB1, Milton and aPKC. These cargos bind
      to the Sisyphus FERM domain, and their binding is in some cases mutually
      exclusive. Our data suggest a mechanism for Sisyphus in which it maintains a
      balance between actin and microtubule cytoskeleton components, thereby
      contributing to cytoskeletal cross-talk necessary for regulating filopodial
      dynamics during dorsal closure.

PMID- 18045838
TI  - Matrix metalloproteinases promote motor axon fasciculation in the Drosophila
      embryo.
AB  - Matrix metalloproteinases (MMPs) are a large conserved family of extracellular
      proteases, a number of which are expressed during neuronal development and
      upregulated in nervous system diseases. Primarily on the basis of studies using
      pharmaceutical inhibitors, MMPs have been proposed to degrade the extracellular
      matrix to allow growth cone advance during development and hence play largely
      permissive roles in axon extension. Here we show that MMPs are not required for
      axon extension in the Drosophila embryo, but rather are specifically required for
      the execution of several stereotyped motor axon pathfinding decisions. The
      Drosophila genome contains only two MMP homologs, Mmp1 and Mmp2. We isolated Mmp1
      in a misexpression screen to identify molecules required for motoneuron
      development. Misexpression of either MMP inhibits the regulated
      separation/defasciculation of motor axons at defined choice points. Conversely,
      motor nerves in Mmp1 and Mmp2 single mutants and Mmp1 Mmp2 double mutant embryos
      are loosely bundled/fasciculated, with ectopic axonal projections. Quantification
      of these phenotypes reveals that the genetic requirement for Mmp1 and Mmp2 is
      distinct in different nerve branches, although generally Mmp2 plays the
      predominant role in pathfinding. Using both an endogenous MMP inhibitor and MMP
      dominant-negative constructs, we demonstrate that MMP catalytic activity is
      required for motor axon fasciculation. In support of the model that MMPs promote
      fasciculation, we find that the defasciculation observed when MMP activity is
      compromised is suppressed by otherwise elevating interaxonal adhesion -- either
      by overexpressing Fas2 or by reducing Sema-1a dosage. These data demonstrate that
      MMP activity is essential for embryonic motor axon fasciculation.

PMID- 18045837
TI  - The E1 ubiquitin-activating enzyme Uba1 in Drosophila controls apoptosis
      autonomously and tissue growth non-autonomously.
AB  - Ubiquitination is an essential process regulating turnover of proteins for basic
      cellular processes such as the cell cycle and cell death (apoptosis).
      Ubiquitination is initiated by ubiquitin-activating enzymes (E1), which activate
      and transfer ubiquitin to ubiquitin-conjugating enzymes (E2). Conjugation of
      target proteins with ubiquitin is then mediated by ubiquitin ligases (E3).
      Ubiquitination has been well characterized using mammalian cell lines and yeast
      genetics. However, the consequences of partial or complete loss of ubiquitin
      conjugation in a multi-cellular organism are not well understood. Here, we report
      the characterization of Uba1, the only E1 in Drosophila. We found that weak and
      strong Uba1 alleles behave genetically differently with sometimes opposing
      phenotypes. Whereas weak Uba1 alleles protect cells from cell death, clones of
      strong Uba1 alleles are highly apoptotic. Strong Uba1 alleles cause cell cycle
      arrest which correlates with failure to reduce cyclin levels. Surprisingly,
      clones of strong Uba1 mutants stimulate neighboring wild-type tissue to undergo
      cell division in a non-autonomous manner giving rise to overgrowth phenotypes of
      the mosaic fly. We demonstrate that the non-autonomous overgrowth is caused by
      failure to downregulate Notch signaling in Uba1 mutant clones. In summary, the
      phenotypic analysis of Uba1 demonstrates that impaired ubiquitin conjugation has
      significant consequences for the organism, and may implicate Uba1 as a tumor
      suppressor gene.

PMID- 18045840
TI  - Regulated addition of new myocardial and epicardial cells fosters homeostatic
      cardiac growth and maintenance in adult zebrafish.
AB  - The heart maintains structural and functional integrity during years of continual
      contraction, but the extent to which new cell creation participates in cardiac
      homeostasis is unclear. Here, we assessed cellular and molecular mechanisms of
      cardiac homeostasis in zebrafish, which display indeterminate growth and possess
      an unusual capacity to regenerate after acute cardiac injury. Lowering fish
      density in the aquarium triggered rapid animal growth and robust cardiomyocyte
      proliferation throughout the adult ventricle, greater than that observed during
      slow animal growth or size maintenance. Rapid animal growth also induced strong
      expression of the embryonic epicardial markers raldh2 (aldh1a2) and tbx18 in
      adult epicardial tissue. Pulse-chase dye labeling experiments revealed that the
      epicardium recurrently contributes cells to the ventricular wall, indicating an
      active homeostatic process. Inhibition of signaling by Fibroblast growth factors
      (Fgfs) decreased this epicardial supplementation of the ventricular wall in
      growing zebrafish, and led to spontaneous ventricular scarring in animals
      maintaining cardiac size. Our results demonstrate that the adult zebrafish
      ventricle grows and is maintained by cardiomyocyte hyperplasia, and that
      epicardial cells are added to the ventricle in an Fgf-dependent fashion to
      support homeostasis.

PMID- 18045839
TI  - A novel promoter-tethering element regulates enhancer-driven gene expression at
      the bithorax complex in the Drosophila embryo.
AB  - A key question in our understanding of the cis-regulation of gene expression
      during embryonic development has been the molecular mechanism that directs
      enhancers to specific promoters within a gene complex. Promoter competition and
      insulators are thought to play a role in regulating these interactions. In the
      bithorax complex of Drosophila, the IAB5 enhancer is located 55 kb 3' of the
      Abdominal-B (Abd-B) promoter and 48 kb 5' of the abdominal-A (abd-A) promoter.
      Although roughly equidistant from the two promoters, IAB5 specifically interacts
      only with the Abdominal-B promoter, even though the enhancer and promoter are
      separated by at least two insulators. Here we demonstrate that a 255 bp element,
      located 40 bp 5' of the Abd-B transcriptional start site, has a novel cis
      regulatory activity as it is able to tether IAB5 to the Abd-B promoter in
      transgenic embryos. The tethering element is sufficient to direct IAB5 to an
      ectopic promoter in competition assays. Deletion of the promoter-tethering
      element results in the redirection of enhancer-driven gene expression on
      transgenes. Taken together, these results provide evidence that specific long
      range enhancer-promoter interactions in the bithorax complex are regulated by a
      tethering element 5' of the Abd-B promoter. We discuss a bioinformatic analysis
      of the tethering element across different Drosophila species and a possible
      molecular mechanism by which this element functions. We also examine existing
      evidence that this novel class of cis-regulatory elements might regulate enhancer
      promoter specificity at other gene complexes.

PMID- 18045841
TI  - Chromatin assembly factor 1 regulates the cell cycle but not cell fate during
      male gametogenesis in Arabidopsis thaliana.
AB  - The interdependence of cell cycle control, chromatin remodeling and cell fate
      determination remains unclear in flowering plants. Pollen development provides an
      interesting model, as it comprises only two cell types produced by two sequential
      cell divisions. The first division separates the vegetative cell from the
      generative cell. The generative cell divides and produces the two sperm cells,
      transported to the female gametes by the pollen tube produced by the vegetative
      cell. We show in Arabidopsis thaliana that loss of activity of the Chromatin
      assembly factor 1 (CAF1) pathway causes delay and arrest of the cell cycle during
      pollen development. Prevention of the second pollen mitosis generates a fraction
      of CAF1-deficient pollen grains comprising a vegetative cell and a single sperm
      cell, which both express correctly cell fate markers. The single sperm is
      functional and fertilizes indiscriminately either female gamete. Our results thus
      suggest that pollen cell fate is independent from cell cycle regulation.

PMID- 18045842
TI  - Wnt3a/beta-catenin signaling controls posterior body development by coordinating
      mesoderm formation and segmentation.
AB  - Somitogenesis is thought to be controlled by a segmentation clock, which consists
      of molecular oscillators in the Wnt3a, Fgf8 and Notch pathways. Using conditional
      alleles of Ctnnb1 (beta-catenin), we show that the canonical Wnt3a/beta-catenin
      pathway is necessary for molecular oscillations in all three signaling pathways
      but does not function as an integral component of the oscillator. Small,
      irregular somites persist in abnormally posterior locations in the absence of
      beta-catenin and cycling clock gene expression. Conversely, Notch pathway genes
      continue to oscillate in the presence of stabilized beta-catenin but boundary
      formation is delayed and anteriorized. Together, these results suggest that the
      Wnt3a/beta-catenin pathway is permissive but not instructive for oscillating
      clock genes and that it controls the anterior-posterior positioning of boundary
      formation in the presomitic mesoderm (PSM). The Wnt3a/beta-catenin pathway does
      so by regulating the activation of the segment boundary determination genes Mesp2
      and Ripply2 in the PSM through the activation of the Notch ligand Dll1 and the
      mesodermal transcription factors T and Tbx6. Spatial restriction of Ripply2 to
      the anterior PSM is ensured by the Wnt3a/beta-catenin-mediated repression of
      Ripply2 in posterior PSM. Thus, Wnt3a regulates somitogenesis by activating a
      network of interacting target genes that promote mesodermal fates, activate the
      segmentation clock, and position boundary determination genes in the anterior
      PSM.

PMID- 18045843
TI  - Oocyte regulation of metabolic cooperativity between mouse cumulus cells and
      oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells.
AB  - Oocyte-derived bone morphogenetic protein 15 (BMP15) and growth differentiation
      factor 9 (GDF9) are key regulators of follicular development. Here we show that
      these factors control cumulus cell metabolism, particularly glycolysis and
      cholesterol biosynthesis before the preovulatory surge of luteinizing hormone.
      Transcripts encoding enzymes for cholesterol biosynthesis were downregulated in
      both Bmp15(-/-) and Bmp15(-/-) Gdf9(+/-) double mutant cumulus cells, and in wild
      type cumulus cells after removal of oocytes from cumulus-cell-oocyte complexes.
      Similarly, cholesterol synthesized de novo was reduced in these cumulus cells.
      This indicates that oocytes regulate cumulus cell cholesterol biosynthesis by
      promoting the expression of relevant transcripts. Furthermore, in wild-type mice,
      Mvk, Pmvk, Fdps, Sqle, Cyp51, Sc4mol and Ebp, which encode enzymes required for
      cholesterol synthesis, were highly expressed in cumulus cells compared with
      oocytes; and oocytes, in the absence of the surrounding cumulus cells,
      synthesized barely detectable levels of cholesterol. Furthermore, coincident with
      reduced cholesterol synthesis in double mutant cumulus cells, lower levels were
      also detected in cumulus-cell-enclosed double mutant oocytes compared with wild
      type oocytes. Levels of cholesterol synthesis in double mutant cumulus cells and
      oocytes were partially restored by co-culturing with wild-type oocytes. Together,
      these results indicate that mouse oocytes are deficient in synthesizing
      cholesterol and require cumulus cells to provide products of the cholesterol
      biosynthetic pathway. Therefore, oocyte-derived paracrine factors, particularly,
      BMP15 and GDF9, promote cholesterol biosynthesis in cumulus cells, probably as
      compensation for oocyte deficiencies in cholesterol production.

PMID- 18045844
TI  - NG2 cells generate both oligodendrocytes and gray matter astrocytes.
AB  - NG2 glia constitute a fourth major glial cell type in the mammalian central
      nervous system (CNS) that is distinct from other cell types. Although
      circumstantial evidence suggests that some NG2 glia differentiate into
      oligodendrocytes, their in vivo fate has not been directly examined. We have used
      the bacterial artificial chromosome (BAC) modification technique to generate
      transgenic mice that express DsRed or Cre specifically in NG2-expressing (NG2+)
      cells. In NG2DsRedBAC transgenic mice, DsRed was expressed specifically in NG2+
      cells throughout the postnatal CNS. When the differentiation potential of NG2+
      cells in vitro was examined using DsRed+NG2+ cells purified from perinatal
      transgenic brains, the majority of the cells either remained as NG2+ cells or
      differentiated into oligodendrocytes. In addition, DsRed+NG2+ cells also
      differentiated into astrocytes. The in vivo fate of NG2 glia was examined in mice
      that were double transgenic for NG2creBAC and the Cre reporter Z/EG. In the
      double transgenic mice, the Cre reporter EGFP was detected in myelinating
      oligodendrocytes and in a subpopulation of protoplasmic astrocytes in the gray
      matter of ventrolateral forebrain but not in fibrous astrocytes of white matter.
      These observations suggest that NG2+ cells are precursors of oligodendrocytes and
      some protoplasmic astrocytes in gray matter.

PMID- 18045845
TI  - Calcium fluxes in dorsal forerunner cells antagonize beta-catenin and alter left
      right patterning.
AB  - Establishment of the left-right axis is essential for normal organ morphogenesis
      and function. Ca(2+) signaling and cilia function in the zebrafish Kuppfer's
      Vesicle (KV) have been implicated in laterality. Here we describe an endogenous
      Ca(2+) release event in the region of the KV precursors (dorsal forerunner cells,
      DFCs), prior to KV and cilia formation. Manipulation of Ca(2+) release to disrupt
      this early flux does not impact early DFC specification, but results in altered
      DFC migration or cohesion in the tailbud at somite stages. This leads to
      disruption of KV formation followed by bilateral expression of asymmetrical
      genes, and randomized organ laterality. We identify beta-catenin inhibition as a
      Ca(2+)-signaling target and demonstrate that localized loss of Ca(2+) within the
      DFC region or DFC-specific activation of beta-catenin is sufficient to alter
      laterality in zebrafish. We identify a previously unknown DFC-like cell
      population in Xenopus and demonstrate a similar Ca(2+)-sensitive stage. As in
      zebrafish, manipulation of Ca(2+) release results in ectopic nuclear beta-catenin
      and altered laterality. Overall, our data support a conserved early Ca(2+)
      requirement in DFC-like cell function in zebrafish and Xenopus.

PMID- 18045846
TI  - Work stress and health in primary health care physicians and hospital physicians.
AB  - OBJECTIVE: In order to understand the reasons for the low priority given to work
      in primary health care among physicians, we studied differences in work stress,
      health and health related lifestyles between general practitioners (GPs) and
      hospital physicians. METHOD: A cohort of 226 GPs and 523 consultants from Finland
      responded to a questionnaire survey. The responses were linked to data on
      registered sickness absence. RESULTS: Compared with consultants, GPs reported
      higher job strain (OR 1.76, 95% CI 1.23 to 2.53) and perceived work overload (OR
      2.29, 95% CI 1.65 to 3.16) but were less likely to report poor team climate (OR
      0.65, 95% CI 0.46 to 0.91), procedural injustice (OR 0.49, 95% CI 0.34 to 0.72)
      and interactional injustice (OR 0.62, 95% CI 0.44 to 0.88). There were only small
      differences in lifestyle, perceived health, psychological distress and long sick
      leaves between GPs and consultants. Short sick leaves were more common among GPs,
      but this difference disappeared after controlling for work characteristics.
      CONCLUSION: In relation to the current recruitment crisis in primary health care
      and the studied working conditions, job strain and heavy workload outweigh the
      attractiveness of a good working climate and low organisational injustice. The
      non-significant differences in health may indicate that there are no differences
      in total work stress between GPs and consultants. In tackling the recruitment
      problems in the field of health care, it is of particular importance to be aware
      of the sector specific difficulties in working conditions.

PMID- 18045847
TI  - Work in the textile industry in Spain and bladder cancer.
AB  - BACKGROUND/OBJECTIVE: Textile manufacturing is a complex industry that has
      frequently been associated with bladder cancer. However, results have not been
      consistent. This study investigated the risk of bladder cancer in Spanish textile
      workers. METHODS: We analysed data from a multicentre hospital-based case-control
      study carried out in Spain (1998-2001) including 1219 cases of bladder cancer and
      1271 controls. Of those, 126 cases and 122 controls reported a history of
      employment in the textile industry. Lifetime occupational history was obtained
      using a computer-assisted personal interview. Occupations, locations and
      materials used in the textile industry were assessed using a detailed
      questionnaire and expert assessment. RESULTS: Overall, no increased risk of
      bladder cancer was found for textile workers, including duration of employment
      analysis. Increased risks were observed for weavers (OR = 1.82, 95% CI 0.95 to
      3.47), for workers in winding/warping/sizing (OR 4.11, 95% CI 1.58 to 10.71) and
      for those exposed to synthetic materials (OR 1.89, 95% CI 1.00 to 3.56). Working
      for more than 10 years appeared to be associated with an increased risk for
      weavers (OR 2.27, 95% CI 0.97 to 5.34), for those who had ever worked in
      winding/warping/sizing (OR 11.03, 95% CI 1.37, 88.89), for workers in the weaving
      room (OR 2.94, 95% CI 1.24 to 7.01) and for those exposed to synthetic (OR 2.62,
      95% CI 1.14 to 6.01) or cotton (OR 2.00, 95% CI 1.04 to 3.87) materials.
      Statistically significant higher risks were also found for specific combinations
      of occupations or locations with exposure to synthetics and cotton. CONCLUSIONS:
      There was no overall increased risk for textile workers, but increased risks were
      found for specific groups of workers. Our findings indicate that observed risks
      in previous studies may be better evaluated by analysis of materials used or
      section worked within the industry and occupation.

PMID- 18045848
TI  - Mortality of former crocidolite (blue asbestos) miners and millers at Wittenoom.
AB  - BACKGROUND: Blue asbestos was mined and milled at Wittenoom in Western Australia
      between 1943 and 1966. METHODS: Nearly 7000 male workers who worked at the
      Wittenoom mine and mill have been followed up using death and cancer registries
      throughout Australia and Italy to the end of 2000. Person-years at risk were
      derived using two censoring dates in order to produce minimum and maximum
      estimates of asbestos effect. Standardised mortality ratios (SMRs) compare the
      mortality of the former Wittenoom workers with the Western Australian male
      population. RESULTS: There have been 190 cases of pleural and 32 cases of
      peritoneal mesothelioma in this cohort of former workers at Wittenoom. Mortality
      from lung cancer (SMR = 1.52), pneumoconiosis (SMR = 15.5), respiratory diseases
      (SMR = 1.58), tuberculosis (SMR = 3.06), digestive diseases (SMR = 1.47),
      alcoholism (SMR = 2.24) and symptoms, signs and ill defined conditions (SMR =
      2.00) were greater in this cohort compared to the Western Australian male
      population. CONCLUSION: Asbestos related diseases, particularly malignant
      mesothelioma, lung cancer and pneumoconiosis, continue to be the main causes of
      excess mortality in the former blue asbestos miners and millers of Wittenoom.

PMID- 18045849
TI  - Fibrillary glomerulonephritis and immunotactoid glomerulopathy.
AB  - Fibrillary glomerulonephritis is a now widely recognized diagnostic entity,
      occurring in approximately 1% of native kidney biopsies in several large biopsy
      series obtained from Western countries. The distinctive features are infiltration
      of glomerular structures by randomly arranged fibrils similar in appearance but
      larger than amyloid fibrils and the lack of staining with histochemical dyes
      typically reactive with amyloid. It is widely but not universally recognized to
      be distinct from immunotactoid glomerulopathy, an entity characterized by
      glomerular deposits of immunoglobulin with substructural organization as
      microtubules and with clinical associations with lymphoplasmacytic disorders. The
      pathophysiologic basis for organization of the glomerular deposits as fibrils or
      microtubules in these entities remains obscure.

PMID- 18045850
TI  - Activation of adenosine 2A receptors preserves structure and function of
      podocytes.
AB  - Adenosine 2A receptor (A(2A)R) activation was recently shown to be renoprotective
      in diabetic nephropathy. A(2A)R are found in glomeruli and have been shown to
      associate with the podocyte cytoskeletal protein alpha-actinin-4, but the effect
      of their activation on podocyte structure and function is unknown. Podocyte
      injury was induced in C57BL/6 mice with puromycin aminonucleoside, and the
      selective A(2A)R agonist ATL313 was found to attenuate the resulting albuminuria
      and foot process fusion. The selective A(2A)R antagonist ZM241385 reversed the
      effects of ATL313. In vitro, A(2A)R mRNA and protein were expressed in a
      conditionally immortalized podocyte cell line, and A(2A)R-like immunoreactivity
      co-localized with the actin cytoskeleton. Treatment with ATL313 also blocked the
      increased podocyte permeability to albumin and disruption of the actin
      cytoskeleton that accompanied puromycin aminonucleoside-induced injury in vitro.
      ATL313 was ineffective, however, in the presence of the A(2A)R antagonist and in
      A(2A)R-deficient podocytes. It was concluded that A(2A)R activation reduces
      glomerular proteinuria, at least in part, by preserving the normal structure of
      podocyte foot processes, slit diaphragms, and actin cytoskeleton.

PMID- 18045851
TI  - Anti-inflammatory renoprotective effect of clopidogrel and irbesartan in chronic
      renal injury.
AB  - Recent evidence suggests that platelet activation and angiotensin II may each
      contribute to glomerular inflammation and fibrosis. Clopidogrel inhibits platelet
      activation and may also reduce inflammation. This study investigated the anti
      inflammatory and renoprotective effects of clopidogrel and irbesartan in the five
      sixths nephrectomy rat model of chronic kidney disease. After 8 wk of treatment,
      24-h proteinuria, serum creatinine, and histologic scores of glomerular sclerosis
      and tubulointerstitial damage were significantly lower in treated compared with
      untreated rats. Clopidogrel/irbesartan combination therapy had greater effects
      than either drug alone. Rats that underwent five-sixths nephrectomy had higher
      markers of platelet activation (plasma GMP-140 and renal cortical fibrin
      deposition) than sham-operated rats, and clopidogrel attenuated these effects.
      Clopidogrel and irbesartan similarly reduced the accumulation of ED-1-expressing
      macrophages in the cortical glomeruli and the interstitium. Combination therapy
      almost completely abolished macrophage infiltration and attenuated the expression
      of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, TGF
      beta(1), and connective tissue growth factor. In conclusion, combination
      treatment with clopidogrel and irbesartan, more so than either alone, decreases
      early renal injury induced by five-sixths nephrectomy by inhibiting renal
      inflammation.

PMID- 18045852
TI  - A three-dimensional quantitative structure-activity analysis of a new class of
      bisphenol topoisomerase IIalpha inhibitors.
AB  - After the identification of a new lead bisphenol compound that had good
      topoisomerase IIalpha (EC 5.99.1.3) inhibitory activity, a series of bisphenol
      analogs were synthesized and tested to identify the structural features that were
      responsible for their activity. The bisphenols represent a new structural class
      of topoisomerase II inhibitor that potently inhibited the growth of Chinese
      hamster ovary and K562 leukemia cells in the low micromolar range. The fact that
      cell growth inhibition was significantly correlated with topoisomerase IIalpha
      inhibition suggests that the catalytic inhibition of topoisomerase IIalpha
      probably contributed to their growth inhibitory activity. Only one of the
      bisphenols (O3OH) tested significantly induced topoisomerase IIalpha-mediated
      cleavage of DNA. Most of the bisphenols displayed only low-fold cross-resistance
      to a K562 subline containing reduced levels of topoisomerase IIalpha Thus, it is
      likely that most of the bisphenols inhibited cell growth, not by acting as
      topoisomerase II poisons, but rather by acting as catalytic inhibitors of
      topoisomerase IIalpha. Three-dimensional quantitative structure-activity analysis
      (3D-QSAR) was carried out on the bisphenols using comparative molecular field
      analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) to
      determine the structural features responsible for their activity. The CoMSIA
      analysis of the topoisomerase IIalpha inhibitory activity yielded a statistically
      significant model upon partial least-squares analyses. The 3D-QSAR CoMSIA
      analysis showed that polar meta hydrogen bond acceptor substituents on the phenyl
      rings favored inhibition of topoisomerase IIalpha. For the hydrogen bond donor
      field, para- and meta-substituted hydroxyl groups favored inhibition. Hydrophobic
      substituents on the bridge atoms disfavored inhibition.

PMID- 18045853
TI  - Plasticity of adenylyl cyclase-related signaling sequelae after long-term
      morphine treatment.
AB  - Adaptations to long-term morphine treatment resulting in tolerance are protective
      by counteracting the consequences of sustained opioid receptor activation.
      Consequently, the manifestation of specific adenylyl cyclase (AC)-related
      neurochemical sequelae of long-term morphine treatment should depend on the
      consequences of short-term mu-opioid receptor (MOR) activation. We tested this by
      comparing complementary chemical sequelae of long-term morphine treatment among
      cells in which short-term MOR activation inhibited instead of stimulated AC
      activity. Short-term activation of MOR in Chinese hamster ovary (CHO) cells
      stably transfected with MOR (MOR-CHO) inhibits AC activity. Long-term morphine
      treatment of these cells increased AC and Gbeta phosphorylation, membrane protein
      kinase Cgamma (PKCgamma) translocation, and MOR G(s) association. All converge,
      shifting the consequences of short-term MOR activation from Galpha(i)/Galpha(o)
      inhibitory to AC stimulatory signaling. In contrast, overexpression of the
      Gbetagamma-stimulated AC isoform AC2 (which converted MOR-coupled inhibition to
      stimulation of AC) eliminated or reversed these adaptations to long-term morphine
      treatment; it negated the increase in Gbeta phosphorylation and PKCgamma
      translocation while reversing the increase in AC phosphorylation and MOR G(s)
      association. These adaptations greatly attenuated MOR-coupled stimulation of AC
      activity. Altered overexpression of AC protein per se was not a confounding
      factor because MOR-CHO overexpressing AC1, which is inhibited by short-term MOR
      activation, manifested adaptations to long-term morphine treatment qualitatively
      identical with those of MOR-CHO. These results reveal that adaptations elicited
      by long-term morphine treatment depend on the effects of short-term MOR
      activation. This dynamic and pliable nature of tolerance mechanisms could
      represent a new paradigm for pharmacotherapeutics.

PMID- 18045854
TI  - Caveolin regulates kv1.5 trafficking to cholesterol-rich membrane microdomains.
AB  - The targeting of ion channels to cholesterol-rich membrane microdomains has
      emerged as a novel mechanism of ion channel localization. Previously, we reported
      that Kv1.5, a prominent cardiovascular K(+) channel alpha-subunit, localizes to
      caveolar microdomains. However, the mechanisms regulating Kv1.5 targeting and the
      functional significance of this localization are largely unknown. In this study,
      we demonstrate a role for caveolin in the trafficking of Kv1.5 to lipid raft
      microdomains where cholesterol modulates channel function. In cells lacking
      endogenous caveolin-1 or -3, the association of Kv1.5 with low-density, detergent
      resistant membrane fractions requires coexpression with exogenous caveolin, which
      can form channel-caveolin complexes. Caveolin is not required for cell surface
      expression, however, and caveolin-trafficking mutants sequester Kv1.5, but not
      Kv2.1, in intracellular compartments, resulting in a loss of functional cell
      surface channel. Coexpression with wild type caveolin-1 does not alter Kv1.5
      current density; rather, it induces depolarizing shifts in steady-state
      activation and inactivation. These shifts are analogous to those produced by
      elevation of membrane cholesterol. Together, these results show that caveolin
      modulates channel function by regulating trafficking to cholesterol-rich membrane
      microdomains.

PMID- 18045855
TI  - Ventricular non-compaction--a frequently ignored finding?

PMID- 18045856
TI  - Phospholamban knockout increases CaM kinase II activity and intracellular Ca2+
      wave activity and alters contractile responses of murine gastric antrum.
AB  - Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca(2+)-ATPase
      (SERCA), and this inhibition is relieved by Ca(2+) calmodulin-dependent protein
      kinase II (CaM kinase II) phosphorylation. We previously reported significant
      differences in contractility, SR Ca(2+) release, and CaM kinase II activity in
      gastric fundus smooth muscles as a result of PLB phosphorylation by CaM kinase
      II. In this study, we used PLB-knockout (PLB-KO) mice to directly examine the
      effect of PLB absence on contractility, CaM kinase II activity, and intracellular
      Ca(2+) waves in gastric antrum smooth muscles. The frequencies and amplitudes of
      spontaneous phasic contractions were elevated in antrum smooth muscle strips from
      PLB-KO mice. Bethanecol increased the amplitudes of phasic contractions in antrum
      smooth muscles from both control and PLB-KO mice. Caffeine decreased and
      cyclopiazonic acid (CPA) increased the basal tone of antrum smooth muscle strips
      from PLB-KO mice, but the effects were less pronounced compared with control
      strips. The CaM kinase II inhibitor KN-93 was less effective at inhibiting
      caffeine-induced relaxation in antrum smooth muscle strips from PLB-KO mice. CaM
      kinase II autonomous activity was elevated, and not further increased by
      caffeine, in antrum smooth muscles from PLB-KO mice. Similarly, the intracellular
      Ca(2+) wave frequency was elevated, and not further increased by caffeine, in
      antrum smooth muscles from PLB-KO mice. These findings suggest that PLB is an
      important modulator of gastric antrum smooth muscle contractility by modulation
      of SR Ca(2+) release and CaM kinase II activity.

PMID- 18045858
TI  - Battleground: chronic kidney disorders mineral and bone disease--calcium
      obsession, vitamin d, and binder confusion.
AB  - Renal osteodystrophy is a significant complication in chronic kidney disease.
      This condition is referred to as mineral and bone disorders in chronic kidney
      disease, mainly because of its wider ranging impact, including an association
      with increased mortality and non-bone-related morbidity. Because most of the
      abnormalities that characterize mineral and bone disorders in chronic kidney
      disease (e.g., hyperphosphatemia, secondary hyperparathyroidism) are amenable to
      therapeutic interventions, this field has also been in the cross-hairs of many
      pharmaceutical companies. The advent of a number of new therapeutic options for
      mineral and bone disorders in chronic kidney disease has broadened our
      armamentarium but has also resulted in an intense marketing battle between
      pharmaceutical companies. The paucity of randomized, controlled trials in this
      field has allowed the various companies to promote unilaterally data that fit
      their needs and to attempt to discredit data that support their competitors'
      products. Although this attitude is expected and regarded as acceptable in a
      consumer society, on a scientific level, it has resulted in a polarized and often
      confused audience: The practicing nephrologists. This article provides a
      historical overview of how the field of mineral and bone disorders in chronic
      kidney disease has evolved from a pharmaceutical standpoint, with a critical
      emphasis of the key moments that resulted in the current acrimonious climate.
      Also assessed is what the key unanswered questions are in this field, and
      practical solutions to the discussed issues are provided.

PMID- 18045857
TI  - Increasing alpha 7 beta 1-integrin promotes muscle cell proliferation, adhesion,
      and resistance to apoptosis without changing gene expression.
AB  - The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by
      associating laminin in the extracellular matrix with the actin cytoskeleton.
      Several human muscular dystrophies arise from defects in the components of this
      complex. The alpha(7)beta(1)-integrin also binds laminin and links the
      extracellular matrix with the cytoskeleton. Enhancement of alpha(7)-integrin
      levels alleviates pathology in mdx/utrn(-/-) mice, a model of Duchenne muscular
      dystrophy, and thus the integrin may functionally compensate for the absence of
      dystrophin. To test whether increasing alpha(7)-integrin levels affects
      transcription and cellular functions, we generated alpha(7)-integrin-inducible
      C2C12 cells and transgenic mice that overexpress the integrin in skeletal muscle.
      C2C12 myoblasts with elevated levels of integrin exhibited increased adhesion to
      laminin, faster proliferation when serum was limited, resistance to staurosporine
      induced apoptosis, and normal differentiation. Transgenic expression of eightfold
      more integrin in skeletal muscle did not result in notable toxic effects in vivo.
      Moreover, high levels of alpha(7)-integrin in both myoblasts and in skeletal
      muscle did not disrupt global gene expression profiles. Thus increasing integrin
      levels can compensate for defects in the extracellular matrix and cytoskeleton
      linkage caused by compromises in the dystrophin-glycoprotein complex without
      triggering apparent overt negative side effects. These results support the use of
      integrin enhancement as a therapy for muscular dystrophy.

PMID- 18045859
TI  - Serum albumin is strongly associated with erythropoietin sensitivity in
      hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: In hemodialysis patients, the hematological response
      to erythropoietin (epo) is variable and clinical factors that explain this
      variability are incompletely understood. We tested the hypothesis that the
      variability in hemoglobin (Hgb) response (epo sensitivity) is determined by key
      nutritional, inflammation, and oxidative stress markers. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Eighty-two consecutive patients on hemodialysis had
      3 consecutive monthly predialysis evaluations of Hgb, total white blood cell
      (WBC) count, serum albumin, malondialdehyde (MDA), and monocyte chemoattractant
      protein-1 (MCP1). We analyzed the time course of Hgb in relationship to serum
      albumin, WBC, MDA, MCP1, epo and iron administration, and tests of iron
      sufficiency in a linear growth curve model. RESULTS: Subjects with higher Hgb had
      a fall in Hgb and vice versa, regressing to a mean Hgb (SD) of 11.8 g/dl (1.8
      g/dl). Whereas the average slope of Hgb was flat, the SD of slopes was 0.63 g/dl,
      which explained 39% of the variance in Hgb. Nonuse of epo was associated with a
      mean Hgb change of -0.18 g/dl (95% confidence interval [CI] -0.26 to -0.10) per
      10,000 IU epo/mo (P < 0.05). Epo use was associated with steeper rate of change
      at 0.04 g/dl per mo per 10,000 IU (95% CI 0.01 to 0.07) (P < 0.01). Hgb at
      baseline was 0.73 g/dl higher for each 1-g/dl increase in albumin, and the rate
      of change increased by 0.49 g/dl per mo for each 1-g/dl increase in albumin
      concentration. WBC, MDA, or MCP1 had no role in predicting the baseline Hgb or
      its change over time. CONCLUSIONS: Serum albumin concentration is an important
      predictor of both baseline Hgb and epo sensitivity in chronic hemodialysis
      patients. Factors that improve serum albumin may also improve Hgb in hemodialysis
      patients.

PMID- 18045860
TI  - Toxic alcohol ingestions: clinical features, diagnosis, and management.
AB  - Alcohol-related intoxications, including methanol, ethylene glycol, diethylene
      glycol, and propylene glycol, and alcoholic ketoacidosis can present with a high
      anion gap metabolic acidosis and increased serum osmolal gap, whereas isopropanol
      intoxication presents with hyperosmolality alone. The effects of these
      substances, except for isopropanol and possibly alcoholic ketoacidosis, are due
      to their metabolites, which can cause metabolic acidosis and cellular
      dysfunction. Accumulation of the alcohols in the blood can cause an increment in
      the osmolality, and accumulation of their metabolites can cause an increase in
      the anion gap and a decrease in serum bicarbonate concentration. The presence of
      both laboratory abnormalities concurrently is an important diagnostic clue,
      although either can be absent, depending on the time after exposure when blood is
      sampled. In addition to metabolic acidosis, acute renal failure and neurologic
      disease can occur in some of the intoxications. Dialysis to remove the
      unmetabolized alcohol and possibly the organic acid anion can be helpful in
      treatment of several of the alcohol-related intoxications. Administration of
      fomepizole or ethanol to inhibit alcohol dehydrogenase, a critical enzyme in
      metabolism of the alcohols, is beneficial in treatment of ethylene glycol and
      methanol intoxication and possibly diethylene glycol and propylene glycol
      intoxication. Given the potentially high morbidity and mortality of these
      intoxications, it is important for the clinician to have a high degree of
      suspicion for these disorders in cases of high anion gap metabolic acidosis,
      acute renal failure, or unexplained neurologic disease so that treatment can be
      initiated early.

PMID- 18045861
TI  - Removal of the protein-bound solutes indican and p-cresol sulfate by peritoneal
      dialysis.
AB  - BACKGROUND AND OBJECTIVES: Protein-bound solutes are poorly cleared by peritoneal
      dialysis. We examined the hypothesis that plasma concentrations of bound solutes
      would therefore rise as residual renal function is lost. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Clearances of urea indican and p-cresol sulfate
      were measured in peritoneal dialysis patients with and without residual function.
      RESULTS: In patients with residual function, protein binding restricted the
      peritoneal indican and p-cresol sulfate clearances to 0.3 +/- 0.1 ml/min, as
      compared to the peritoneal urea clearance of 5.5 +/- 1.1 ml/min. The urinary
      indican and p-cresol sulfate clearances of 2.7 +/- 2.5 and 1.3 +/- 1.0 ml/min
      were closer to the urinary urea clearance of 3.9 +/- 2.2 ml/min, reflecting the
      superior ability of native kidney function to clear bound solutes. Urinary
      clearance thus provided the majority of the total indican and p-cresol sulfate
      clearances of 3.0 +/- 2.5 and 1.6 +/- 1.0 ml/min in patients with residual
      function but the minority of total urea clearance of 9.4 +/- 2.2 ml/min. Loss of
      residual function lowered the total clearances for indican and p-cresol sulfate
      to 0.5 +/- 0.2 and 0.4 +/- 0.2 ml/min, whereas the urea clearance fell only
      slightly. However there was only a modest increase in the plasma indican level
      and no increase in the plasma p-cresol sulfate level in patients with no residual
      function because reduction in the daily removal of these solutes accompanied the
      reduction in their total clearance rates. CONCLUSIONS: Reduction in the removal
      of indican and p-cresol sulfate kept plasma levels from rising markedly when
      residual function was lost.

PMID- 18045862
TI  - Hemoglobin level variability: associations with mortality.
AB  - BACKGROUND/OBJECTIVES: Awareness of hemoglobin level variability in dialysis
      patients is increasing, as is interest in its potential implications. In this
      retrospective, national study of associations between the degree of hemoglobin
      level variability in the first 6 mo of 2004 and subsequent mortality rates in the
      following 6 mo, 159,720 hemodialysis patients receiving epoetin therapy were
      studied. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: Monthly hemoglobin values
      were categorized as low (L; < 11 g/dl), intermediate (I; 11 to 12.5 g/dl), and
      high (H; >12.5 g/dl). Variability groups were classified on the basis of the
      lowest and highest hemoglobin categories seen during the 6-mo observation period:
      low-low (L-L), 1.4%; intermediate-intermediate (I-I), 6.0%; high-high (H-H),
      2.3%; low-intermediate (L-I), 18.3%; intermediate-high (I-H), 31.7%, and low-high
      (L-H), 40.2%. RESULTS: On multivariate analysis, adjusted hazards ratios for
      subsequent mortality events were as follows: I-I, 1.0 (reference category); I-H,
      1.02 (95% confidence interval [CI] 0.95 to 1.11); H-H, 1.06 (95% CI 0.93 to
      1.21); L-H, 1.19 (95% CI 1.10 to 1.28); L-I, 1.44 (95% CI 1.33 to 1.56), and L-L,
      2.18 (95% CI 1.93 to 2.45). Persistently and transiently low hemoglobin levels
      and highly variable hemoglobin levels were associated with increased risk of
      death; transiently and persistently high hemoglobin levels were not associated
      with increased risk of death. Bayesian modeling indicated that > or =3 mo with
      hemoglobin levels <11 g/dl may be associated with of increased risk of death.
      CONCLUSIONS: Number of months with hemoglobin values below the target range,
      rather than hemoglobin variability itself, may be the primary driver of increased
      risk of death. Further research is needed to distinguish cause from effect and to
      understand the underlying mechanisms.

PMID- 18045863
TI  - Comprehensive analysis of the factors contributing to the stability and
      solubility of autonomous human VH domains.
AB  - We report a comprehensive analysis of sequence features that allow for the
      production of autonomous human heavy chain variable (V(H)) domains that are
      stable and soluble in the absence of a light chain partner. Using combinatorial
      phage-displayed libraries and conventional biophysical methods, we analyzed the
      entire former light chain interface and the third complementarity determining
      region (CDR3). Unlike the monomeric variable domains of camelid heavy chain
      antibodies (V(H)H domains), in which autonomous behavior depends on interactions
      between the hydrophobic former light chain interface and CDR3, we find that the
      stability of many in vitro evolved V(H) domains is essentially independent of the
      CDR3 sequence and instead derives from mutations that increase the hydrophilicity
      of the former light chain interface by replacing exposed hydrophobic residues
      with structurally compatible hydrophilic substitutions. The engineered domains
      can be expressed recombinantly at high yield, are predominantly monomeric at high
      concentrations, unfold reversibly, and are even more thermostable than typical
      camelid V(H)H domains. Many of the stabilizing mutations are rare in natural V(H)
      and V(H)H domains and thus could not be predicted by studying natural sequences
      and structures. The results demonstrate that autonomous V(H) domains with
      structural properties beyond the scope of natural frameworks can be derived by
      using non-natural mutations, which differ from those found in camelid V(H)H
      domains. These findings should enable the development of libraries of synthetic
      V(H) domains with CDR3 diversities unconstrained by structural demands.

PMID- 18045864
TI  - The lipid whisker model of the structure of oxidized cell membranes.
AB  - An essential feature of the innate immune system is maintaining cellular
      homeostasis by identifying and removing senescent and apoptotic cells and
      modified lipoproteins. Identification is achieved through the recognition of
      molecular patterns, including structurally distinct oxidized phospholipids, on
      target cells by macrophage receptors. Both the structural nature of the molecular
      patterns recognized and their orientation within membranes has remained elusive.
      We recently described the membrane conformation of an endogenous oxidized
      phospholipid ligand for macrophage scavenger receptor CD36, where the truncated
      oxidized sn-2 fatty acid moiety protrudes into the aqueous phase, rendering it
      accessible for recognition. Herein we examine the generality of this
      conformational motif for peroxidized glycerophospholipids within membranes. Our
      data reveal that the addition of a polar oxygen atom on numerous peroxidized
      fatty acids reorients the acyl chain, whereby it no longer remains buried within
      the membrane interior but rather protrudes into the aqueous compartment.
      Moreover, we show that neither a conformational change in the head group relative
      to the membrane surface nor the presence of a polar head group is essential for
      CD36 recognition of free oxidized phospholipid ligands within membranes. Rather,
      our results suggest the following global phenomenon. As cellular membranes
      undergo lipid peroxidation, such as during senescence or apoptosis, previously
      hydrophobic portions of fatty acids will move from the interior of the lipid
      bilayer to the aqueous exterior. This enables physical contact between pattern
      recognition receptor and molecular pattern ligand. Cell membranes thus "grow
      whiskers" as phospholipids undergo peroxidation, and many of their oxidized fatty
      acids protrude at the surface.

PMID- 18045865
TI  - Amplification of CD95 activation by caspase 8-induced endosomal acidification in
      rat hepatocytes.
AB  - Although in rat hepatocytes CD95 is predominantly located inside the cell with
      almost undetectable immunostaining at the plasma membrane, the addition of CD95
      ligand (CD95L) induces hepatocyte apoptosis, which is preceded by a targeting and
      activation of intracellularly localized CD95 to the plasma membrane including
      formation of the death-inducing signaling complex. This process involves an NADPH
      oxidase-dependent generation of reactive oxygen species (ROS) through a ceramide-
      and protein kinase Czeta-dependent pathway, which leads to an activating
      phosphorylation of p47(phox). The mechanisms underlying CD95L-induced ceramide
      formation were addressed in the present study. It was found that CD95L lowered
      within seconds the apparent vesicular pH from 6.0 to 5.7 in a fluorescein
      isothiocyanate-dextran-accessible endosomal compartment, which was previously
      shown to contain acidic sphingomyelinase, and decreased N-(ethoxycarbonylmethyl)
      6-methoxyquinolinium bromide fluorescence, suggestive for an increase of
      cytosolic [Cl(-)]. Bafilomycin or 4,4'-diisothiocyanostilbene-2,2'-disulfonic
      acid disodium salt largely abolished the CD95L-induced endosomal acidification,
      ceramide formation, and downstream events, such as p47(phox) phosphorylation, ROS
      formation, CD95 activation, and apoptosis. These responses were also abolished
      after knock-down of acidic sphingomyelinase in rat hepatocytes. Interestingly,
      caspase 8 inhibitors abolished these CD95L-induced signaling events, including
      the increase in cytosolic [Cl(-)], endosomal acidification, ceramide formation,
      and ROS generation as well as CD95 targeting to the plasma membrane and CD95
      activation. The data suggest that CD95L initiates a rapid caspase 8-dependent
      endosomal acidification, which triggers ceramide-dependent ROS formation as an
      upstream event of trafficking of intracellularly stored CD95 to the plasma
      membrane. It is concluded that a rapid caspase 8 activation in response to CD95L
      signals to intracellularly stored CD95, which becomes activated and targeted to
      the plasma membrane. This autoamplification of CD95-activation is required for
      apoptosis induction.

PMID- 18045866
TI  - Memo is homologous to nonheme iron dioxygenases and binds an ErbB2-derived
      phosphopeptide in its vestigial active site.
AB  - Memo (mediator of ErbB2-driven cell motility) is a 297-amino-acid protein
      recently shown to co-precipitate with the C terminus of ErbB2 and be required for
      ErbB2-driven cell motility. Memo is not homologous to any known signaling
      proteins, and how it mediates ErbB2 signals is not known. To provide a molecular
      basis for understanding Memo function, we have determined and report here the
      2.1A crystal structure of human Memo and show it be homologous to class III
      nonheme iron-dependent dioxygenases, a structural class that now includes a zinc
      binding protein of unknown function. No metal binding or enzymatic activity can
      be detected for Memo, but Memo does bind directly to a specific ErbB2-derived
      phosphopeptide encompassing Tyr-1227 using its vestigial enzymatic active site.
      Memo thus represents a new class of phosphotyrosine-binding protein.

PMID- 18045867
TI  - A role for basic transcription element-binding protein 1 (BTEB1) in the
      autoinduction of thyroid hormone receptor beta.
AB  - Thyroid hormone (T(3)) induces gene regulation programs necessary for tadpole
      metamorphosis. Among the earliest responses to T(3) are the up-regulation of T(3)
      receptor beta (TRbeta; autoinduction) and BTEB1 (basic transcription element
      binding protein 1). BTEB1 is a member of the Kruppel family of transcription
      factors that bind to GC-rich regions in gene promoters. The proximal promoter of
      the Xenopus laevis TrbetaA gene has seven GC-rich sequences, which led us to
      hypothesize that BTEB1 binds to and regulates TrbetaA. In tadpoles and the frog
      fibroblast-derived cell line XTC-2, T(3) up-regulated Bteb1 mRNA with faster
      kinetics than TrbetaA, and Bteb1 mRNA correlated with increased BTEB1 protein
      expression. BTEB1 bound to GC-rich sequences in the proximal TrbetaA promoter in
      vitro. By using chromatin immunoprecipitation assay, we show that BTEB1
      associates with the TrbetaA promoter in vivo in a T(3) and developmental stage
      dependent manner. Induced expression of BTEB1 in XTC-2 cells caused accelerated
      and enhanced autoinduction of the TrbetaA gene. This enhancement was lost in N
      terminal truncated mutants of BTEB1. However, point mutations in the zinc fingers
      of BTEB1 that destroyed DNA binding did not alter the activity of the protein on
      TrbetaA autoinduction, suggesting that BTEB1 can function in this regard through
      protein-protein interactions. Our findings support the hypothesis that BTEB1
      associates with the TrbetaA promoter in vivo and enhances autoinduction, but this
      action does not depend on its DNA binding activity. Cooperation among the protein
      products of immediate early genes may be a common mechanism for driving
      developmental signaling pathways.

PMID- 18045869
TI  - GDP-4-keto-6-deoxy-D-mannose 3-dehydratase, accommodating a sugar substrate in
      the active site.
AB  - Colitose is a dideoxysugar found in the O-antigen of the lipopolysaccharide that
      coats the outer membrane of some Gram-negative bacteria. Four enzymes are
      required for its production starting from D-mannose-1-phosphate and GTP. The
      focus of this investigation is GDP-4-keto-6-deoxy-D-mannose 3-dehydratase or
      ColD, which catalyzes the removal of the C3'-hydroxyl group from GDP-4-keto-6
      deoxymannose. The enzyme is pyridoxal 5'-phosphate-dependent, but unlike most of
      these proteins, the conserved lysine residue that covalently holds the cofactor
      in the active site is replaced with a histidine residue. Here we describe the
      three-dimensional structure of ColD, determined to 1.7A resolution, whereby the
      active site histidine has been replaced with an asparagine residue. For this
      investigation, crystals of the site-directed mutant protein were grown in the
      presence of GDP-4-amino-4,6-dideoxy-D-mannose (GDP-perosamine). The electron
      density map clearly reveals the presence of the sugar analog trapped in the
      active site as an external aldimine. The active site is positioned between the
      two subunits of the dimer. Whereas the pyrophosphoryl groups of the ligand are
      anchored to the protein via Arg-219 and Arg-331, the hydroxyl groups of the
      hexose only lie within hydrogen bonding distance to ordered water molecules.
      Interestingly, the hexose moiety of the ligand adopts a boat rather than the
      typically observed chair conformation. Activity assays demonstrate that this
      mutant protein cannot catalyze the dehydration step. Additionally, we report data
      revealing that wild-type ColD is able to catalyze the production of GDP-4-keto
      3,6-dideoxymannose using GDP-perosamine instead of GDP-4-keto-6-deoxymannose as a
      substrate.

PMID- 18045868
TI  - Functional role for a conserved aspartate in the Spo0E signature motif involved
      in the dephosphorylation of the Bacillus subtilis sporulation regulator Spo0A.
AB  - Sporulation is a complex developmental system characterizing Gram-positive
      bacteria of the genus Bacillus and Clostridium. In Bacillus subtilis the
      phosphorelay signal transduction system regulates the initiation of sporulation
      by integrating a myriad of positive and negative signals through the action of
      histidine sensor kinases and aspartyl phosphate phosphatases. The Spo0E family of
      phosphatases dephosphorylates the Spo0A response regulator and transcription
      factor of the phosphorelay. In this study we analyzed the role of the Spo0E
      signature motif in protein activity. This family is characterized by a conserved
      signature motif centered around the sequence "SQELD." Alanine scanning
      mutagenesis was carried out on the T(35)IXXSQ ELDCLI(46) residues of B. subtilis
      Spo0E and in vivo and in vitro activities were analyzed. The ability of the
      mutant proteins to interact with Spo0A approximately P was assayed by
      fluorescence resonance energy transfer spectroscopy. The results suggested that
      aspartate 43 has a critical role in Spo0E catalytic activity, whereas the other
      residues have a role in protein conformation and/or interaction with Spo0A.
      Residues Thr(35) and Cys(44) did not seem to have any critical functional or
      structural role. We propose that Asp(43) of Spo0E may function in a manner
      similar to the one proposed for the catalytic mechanisms of nucleotidase members
      of the haloacid dehalogenase family. These proteins use an aspartyl nucleophile
      as their common catalytic strategy and the active site of haloacid dehalogenase
      proteins shares a common geometry and identity of conserved amino acids with the
      active site of response regulators ( Ridder, I. S., and Dijkstra, B. W. (1999)
      Biochem. J. 339, 223-226 ).

PMID- 18045870
TI  - Impact of the polysialyltransferases ST8SiaII and ST8SiaIV on polysialic acid
      synthesis during postnatal mouse brain development.
AB  - Polysialic acid (polySia), a post-translational modification of the neural cell
      adhesion molecule (NCAM), is the key regulator of NCAM-mediated functions and
      crucial for normal brain development, postnatal growth, and survival. Two
      polysialyltransferases, ST8SiaII and ST8SiaIV, mediate polySia biosynthesis. To
      dissect the impact of each enzyme during postnatal brain development, we
      monitored the developmental changes in NCAM polysialylation in wild-type,
      ST8SiaII-, and ST8SiaIV-deficient mice using whole brain lysates obtained at 10
      time points from postnatal days 1 to 21 and from adult mice. In wild-type and
      ST8SiaIV-null brain, polySia biosynthesis kept pace with the rapid increase in
      brain weight until day 9, and nearly all NCAM was polysialylated. Thereafter,
      polySia dropped by approximately 70% within 1 week, accompanied by the first
      occurrence of polySia-free NCAM-140 and NCAM-180. In ST8SiaII-null brain, polySia
      declined immediately after birth, leading to 60% less polySia at day 9 combined
      with the untimely appearance of polySia-free NCAM. Polysialyltransferase
      deficiency did not alter NCAM expression level or isoform pattern. In all three
      genotypes, NCAM-140 and NCAM-180 were expressed at constant levels from days 1 to
      21 and provided the major polySia acceptors. By contrast, NCAM-120 first appeared
      at day 5, followed by a strong up-regulation inverse to the decrease in polySia.
      Together, we provide a comprehensive quantitative analysis of the developmental
      changes in polySia level, NCAM polysialylation status, and polysialyltransferase
      transcript levels and show that the predominant role of ST8SiaII during postnatal
      brain development is restricted to the first 15 days.

PMID- 18045871
TI  - Structural and functional analyses of the severe acute respiratory syndrome
      coronavirus endoribonuclease Nsp15.
AB  - The severe acute respiratory syndrome (SARS) coronavirus encodes several RNA
      processing enzymes that are unusual for RNA viruses, including Nsp15
      (nonstructural protein 15), a hexameric endoribonuclease that preferentially
      cleaves 3' of uridines. We solved the structure of a catalytically inactive
      mutant version of Nsp15, which was crystallized as a hexamer. The structure
      contains unreported flexibility in the active site of each subunit. Substitutions
      in the active site residues serine 293 and proline 343 allowed Nsp15 to cleave at
      cytidylate, whereas mutation of leucine 345 rendered Nsp15 able to cleave at
      purines as well as pyrimidines. Mutations that targeted the residues involved in
      subunit interactions generally resulted in the formation of catalytically
      inactive monomers. The RNA-binding residues were mapped by a method linking
      reversible cross-linking, RNA affinity purification, and peptide fingerprinting.
      Alanine substitution of several residues in the RNA-contacting portion of Nsp15
      did not affect hexamer formation but decreased the affinity of RNA binding and
      reduced endonuclease activity. This suggests a model for Nsp15 hexamer
      interaction with RNA.

PMID- 18045872
TI  - Conformational rearrangement within the soluble domains of the CD4 receptor is
      ligand-specific.
AB  - Ligand binding induces shape changes within the four modular ectodomains (D1-D4)
      of the CD4 receptor, an important receptor in immune signaling. Small angle x-ray
      scattering (SAXS) on both a two-domain and a four-domain construct of the soluble
      CD4 (sCD4) is consistent with known crystal structures demonstrating a bilobal
      and a semi-extended tetralobal Z conformation in solution, respectively.
      Detection of conformational changes within sCD4 as a result of ligand binding was
      followed by SAXS on sCD4 bound to two different glycoprotein ligands: the tick
      saliva immunosuppressor Salp15 and the HIV-1 envelope protein gp120. Ab initio
      modeling of these data showed that both Salp15 and gp120 bind to the D1 domain of
      sCD4 and yet induce drastically different structural rearrangements. Upon
      binding, Salp15 primarily distorts the characteristic lobal architecture of the
      sCD4 without significantly altering the semi-extended shape of the sCD4 receptor.
      In sharp contrast, the interaction of gp120 with sCD4 induces a shape change
      within sCD4 that can be described as a Z-to-U bi-fold closure of the four domains
      across its flexible D2-D3 linker. Placement of known crystal structures within
      the boundaries of the SAXS-derived models suggests that the ligand-induced shape
      changes could be a result of conformational changes within this D2-D3 linker.
      Functionally, the observed shape changes in CD4 receptor causes dissociation of
      lymphocyte kinase from the cytoplasmic domain of Salp15-bound CD4 and facilitates
      an interaction between the exposed V3 loops of CD4-bound gp120 molecule to the
      extracellular loops of its co-receptor, a step essential for HIV-1 viral entry.

PMID- 18045873
TI  - Dynamics of trigger factor interaction with translating ribosomes.
AB  - In all organisms ribosome-associated chaperones assist early steps of protein
      folding. To elucidate the mechanism of their action, we determined the kinetics
      of individual steps of the ribosome binding/release cycle of bacterial trigger
      factor (TF), using fluorescently labeled chaperone and ribosome-nascent chain
      complexes. Both the association and dissociation rates of TF-ribosome complexes
      are modulated by nascent chains, whereby their length, sequence, and folding
      status are influencing parameters. However, the effect of the folding status is
      modest, indicating that TF can bind small globular domains and accommodate them
      within its substrate binding cavity. In general, the presence of a nascent chain
      causes an up to 9-fold increase in the rate of TF association, which provides a
      kinetic explanation for the observed ability of TF to efficiently compete with
      other cytosolic chaperones for binding to nascent chains. Furthermore, a subset
      of longer nascent polypeptides promotes the stabilization of TF-ribosome
      complexes, which increases the half-life of these complexes from 15 to 50 s.
      Nascent chains thus regulate their folding environment generated by ribosome
      associated chaperones.

PMID- 18045874
TI  - Intramolecular and intermolecular fluorescence resonance energy transfer in
      fluorescent protein-tagged Na-K-Cl cotransporter (NKCC1): sensitivity to
      regulatory conformational change and cell volume.
AB  - To examine the structure and function of the Na-K-Cl cotransporter, NKCC1, we
      tagged the transporter with cyan (CFP) and yellow (YFP) fluorescent proteins and
      measured fluorescence resonance energy transfer (FRET) in stably expressing human
      embryonic kidney cell lines. Fluorescent protein tags were added at the N
      terminal residue between the regulatory domain and the membrane domain and within
      a poorly conserved region of the C terminus. Both singly and doubly tagged NKCC1s
      were appropriately trafficked to the cell membrane and were fully functional;
      regulation was normal except when YFP was inserted near the regulatory domain, in
      which case activation occurred only upon incubation with calyculin A. Quenching
      of YFP fluorescence by Cl(-) provided a ratiometric indicator of intracellular
      [Cl(-)]. All of the CFP/YFP NKCC pairs exhibited some level of FRET,
      demonstrating the presence of dimers or higher multimers in functioning NKCC1.
      With YFP near the regulatory domain and CFP in the C terminus, we recorded a 6%
      FRET change signaling the regulatory phosphorylation event. On the other hand,
      when the probe was placed at the extreme N terminus, such changes were not seen,
      presumably due to the length and predicted flexibility of the N terminus.
      Substantial FRET changes were observed contemporaneous with cell volume changes,
      possibly reflective of an increase in molecular crowding upon cell shrinkage.

PMID- 18045875
TI  - Innate immunity to intraphagosomal pathogens is mediated by interferon regulatory
      factor 8 (IRF-8) that stimulates the expression of macrophage-specific Nramp1
      through antagonizing repression by c-Myc.
AB  - Macrophages are a central arm of innate immune defense against intracellular
      pathogens. They internalize microbes into phagosomes where the invaders are being
      killed by oxygen and nitrogen reactive species. Despite this battery of
      antimicrobial molecules, some are able to thrive within the phagosome thus termed
      intraphagosomal pathogens among which are Salmonella, Leishmania, and
      Mycobacteria. In mice, a single dominant gene termed Nramp1/Slc11a1 controls
      innate resistance to such pathogens. This gene is expressed exclusively in
      myeloid cells. Previously, we have shown that the restricted expression of Nramp1
      is regulated by a myeloid cell-specific transcription factor termed IRF-8/ICSBP.
      It is demonstrated here that the induction of Nramp1 expression in activated
      macrophages is accompanied by a promoter shift from a repression state elicited
      by c-Myc to an activation state elicited by the induction of IRF-8 in activated
      macrophages. This transition from repression to activation is facilitated by a
      competitive protein-protein interaction with the transcription factor Miz-1. To
      show that IRF-8 is directly involved in the elimination of intraphagosomal
      pathogens through the regulation of Nramp1 gene expression, we bred wild type as
      well as IRF-8 and Nramp1 null mouse strains and examined macrophages derived from
      bone marrow and peritoneum. Our results clearly show that the absence of IRF-8
      and Nramp1 leads to the same phenotype; defective killing of intraphagosomal
      Salmonella enterica serovar typhimurium and Mycobacterium bovis. Thus, interplay
      between repression and activation state of the Nramp1 promoter mediated by IRF-8
      provides the molecular basis by which macrophages resist intraphagosomal
      pathogens at early stage after infection.

PMID- 18045876
TI  - A topological model of the baseplate of lactococcal phage Tuc2009.
AB  - Phages infecting Lactococcus lactis, a Gram-positive bacterium, are a recurrent
      problem in the dairy industry. Despite their economical importance, the knowledge
      on these phages, belonging mostly to Siphoviridae, lags behind that accumulated
      for members of Myoviridae. The three-dimensional structures of the receptor
      binding proteins (RBP) of three lactococcal phages have been determined recently,
      illustrating their modular assembly and assigning the nature of their bacterial
      receptor. These RBPs are attached to the baseplate, a large phage organelle,
      located at the tip of the tail. Tuc2009 baseplate is formed by the products of 6
      open read frames, including the RBP. Because phage binding to its receptor
      induces DNA release, it has been postulated that the baseplate might be the
      trigger for DNA injection. We embarked on a structural study of the lactococcal
      phages baseplate, ultimately to gain insight into the triggering mechanism
      following receptor binding. Structural features of the Tuc2009 baseplate were
      established using size exclusion chromatography coupled to on-line UV-visible
      absorbance, light scattering, and refractive index detection (MALS/UV/RI).
      Combining the results of this approach with literature data led us to propose a
      "low resolution" model of Tuc2009 baseplate. This model will serve as a knowledge
      base to submit relevant complexes to crystallization trials.

PMID- 18045877
TI  - Heterotrimeric G protein betagamma subunits stimulate FLJ00018, a guanine
      nucleotide exchange factor for Rac1 and Cdc42.
AB  - We previously reported that Gbetagamma signaling regulates cell spreading or cell
      shape change through activation of a Rho family small GTPase, suggesting the
      existence of a Gbetagamma-regulated Rho guanine-nucleotide exchange factor
      (RhoGEF). In this study we examined various RhoGEF clones, found FLJ00018 to
      beaGbetagamma-activated RhoGEF, and investigated the molecular mechanism of
      Gbetagamma-induced activation of Rho family GTPases. Co-expression of the genes
      for FLJ00018 and Gbetagamma enhanced serum response element-mediated gene
      transcription in HEK-293 cells. Combined expression of Gbetagamma and FLJ00018
      significantly induced activation of Rac and Cdc42 but not RhoA. FLJ00018 also
      enhanced gene transcription induced by carbachol-stimulated m2 muscarinic
      acetylcholine receptor, and this enhancement was blocked by pertussis toxin.
      Furthermore, we demonstrated Gbetagamma to interact directly with the N-terminal
      region of FLJ00018 and the N-terminal fragment of this molecule to inhibit serum
      response element-dependent transcription induced by Gbetagamma/FLJ00018 and
      carbachol. In NIH3T3 cells, FLJ00018 enhanced lysophosphatidic acid-induced cell
      spreading, which was also blocked by the N-terminal fragment of FLJ00018. These
      results provide evidence for a signaling pathway by which G(i)-coupled receptor
      specifically induces Rac and Cdc42 activation through direct interaction of
      Gbetagamma with FLJ00018.

PMID- 18045878
TI  - beta2-adrenergic receptor signaling and desensitization elucidated by
      quantitative modeling of real time cAMP dynamics.
AB  - G protein-coupled receptor signaling is dynamically regulated by multiple
      feedback mechanisms, which rapidly attenuate signals elicited by ligand
      stimulation, causing desensitization. The individual contributions of these
      mechanisms, however, are poorly understood. Here, we use an improved fluorescent
      biosensor for cAMP to measure second messenger dynamics stimulated by endogenous
      beta(2)-adrenergic receptor (beta(2)AR) in living cells. beta(2)AR stimulation
      with isoproterenol results in a transient pulse of cAMP, reaching a maximal
      concentration of approximately 10 microm and persisting for less than 5 min. We
      investigated the contributions of cAMP-dependent kinase, G protein-coupled
      receptor kinases, and beta-arrestin to the regulation of beta(2)AR signal
      kinetics by using small molecule inhibitors, small interfering RNAs, and mouse
      embryonic fibroblasts. We found that the cAMP response is restricted in duration
      by two distinct mechanisms in HEK-293 cells: G protein-coupled receptor kinase
      (GRK6)-mediated receptor phosphorylation leading to beta-arrestin mediated
      receptor inactivation and cAMP-dependent kinase-mediated induction of cAMP
      metabolism by phosphodiesterases. A mathematical model of beta(2)AR signal
      kinetics, fit to these data, revealed that direct receptor inactivation by cAMP
      dependent kinase is insignificant but that GRK6/beta-arrestin-mediated
      inactivation is rapid and profound, occurring with a half-time of 70 s. This
      quantitative system analysis represents an important advance toward quantifying
      mechanisms contributing to the physiological regulation of receptor signaling.

PMID- 18045879
TI  - Polyglutamylation is a post-translational modification with a broad range of
      substrates.
AB  - Polyglutamylation is a post-translational modification that generates lateral
      acidic side chains on proteins by sequential addition of glutamate amino acids.
      This modification was first discovered on tubulins, and it is important for
      several microtubule functions. Besides tubulins, only the nucleosome assembly
      proteins NAP1 and NAP2 have been shown to be polyglutamylated. Here, using a
      proteomic approach, we identify a large number of putative substrates for
      polyglutamylation in HeLa cells. By analyzing a selection of these putative
      substrates, we show that several of them can serve as in vitro substrates for two
      of the recently discovered polyglutamylases, TTLL4 and TTLL5. We further show
      that TTLL4 is the main polyglutamylase enzyme present in HeLa cells and that new
      substrates of polyglutamylation are indeed modified by TTLL4 in a cellular
      context. No clear consensus polyglutamylation site could be defined from the
      primary sequence of the here-identified new substrates of polyglutamylation.
      However, we demonstrate that glutamate-rich stretches are important for a protein
      to become polyglutamylated. Most of the newly identified substrates of
      polyglutamylation are nucleocytoplasmic shuttling proteins, including many
      chromatin-binding proteins. Our work reveals that polyglutamylation is a much
      more widespread post-translational modification than initially thought and thus
      that it might be a regulator of many cellular processes.

PMID- 18045880
TI  - Neurotrophic factor neurotrophin-4 regulates ameloblastin expression via full
      length TrkB.
AB  - Neurotrophic factors play an important role in the development and maintenance of
      not only neural but also nonneural tissues. Several neurotrophic factors are
      expressed in dental tissues, but their role in tooth development is not clear.
      Here, we report that neurotrophic factor neurotrophin (NT)-4 promotes
      differentiation of dental epithelial cells and enhances the expression of enamel
      matrix genes. Dental epithelial cells from 3-day-old mice expressed NT-4 and
      three variants of TrkB receptors for neurotrophins (full-length TrkB-FL and
      truncated TrkB-T1 and -T2). Dental epithelial cell line HAT-7 expressed these
      genes, similar to those in dental epithelial cells. We found that NT-4 reduced
      HAT-7 cell proliferation and induced the expression of enamel matrix genes, such
      as ameloblastin (Ambn). Transfection of HAT-7 cells with the TrkB-FL expression
      construct enhanced the NT-4-mediated induction of Ambn expression. This
      enhancement was blocked by K252a, an inhibitor for Trk tyrosine kinases.
      Phosphorylation of ERK1/2, a downstream molecule of TrkB, was induced in HAT-7
      cells upon NT-4 treatment. TrkB-FL but not TrkB-T1 transfection increased the
      phosphorylation level of ERK1/2 in NT-4-treated HAT-7 cells. These results
      suggest that NT-4 induced Ambn expression via the TrkB-MAPK pathway. The p75
      inhibitor TAT-pep5 decreased NT-4-mediated induction of the expression of Ambn,
      TrkB-FL, and TrkB-T1, suggesting that both high affinity and low affinity
      neurotrophin receptors were required for NT-4 activity. We found that NT-4-null
      mice developed a thin enamel layer and had a decrease in Ambn expression. Our
      results suggest that NT-4 regulates proliferation and differentiation of the
      dental epithelium and promotes production of the enamel matrix.

PMID- 18045881
TI  - Potyvirus genome-linked protein, VPg, directly affects wheat germ in vitro
      translation: interactions with translation initiation factors eIF4F and eIFiso4F.
AB  - Potyvirus genome linked protein, VPg, interacts with translation initiation
      factors eIF4E and eIFiso4E, but its role in protein synthesis has not been
      elucidated. We show that addition of VPg to wheat germ extract leads to
      enhancement of uncapped viral mRNA translation and inhibition of capped viral
      mRNA translation. This provides a significant competitive advantage to the
      uncapped viral mRNA. To understand the molecular basis of these effects, we have
      characterized the interaction of VPg with eIF4F, eIFiso4F, and a structured RNA
      derived from tobacco etch virus (TEV RNA). When VPg formed a complex with eIF4F,
      the affinity for TEV RNA increased more than 4-fold compared with eIF4F alone
      (19.4 and 79.0 nm, respectively). The binding affinity of eIF4F to TEV RNA
      correlates with translation efficiency. VPg enhanced eIFiso4F binding to TEV RNA
      1.6-fold (178 nm compared with 108 nm). Kinetic studies of eIF4F and eIFiso4F
      with VPg show approximately 2.6-fold faster association for eIFiso4F.VPg as
      compared with eIF4F.VPg. The dissociation rate was approximately 2.9-fold slower
      for eIFiso4F than eIF4F with VPg. These data demonstrate that eIFiso4F can
      kinetically compete with eIF4F for VPg binding. The quantitative data presented
      here suggest a model where eIF4F.VPg interaction enhances cap-independent
      translation by increasing the affinity of eIF4F for TEV RNA. This is the first
      evidence of direct participation of VPg in translation initiation.

PMID- 18045882
TI  - Osteoblasts directly control lineage commitment of mesenchymal progenitor cells
      through Wnt signaling.
AB  - Lineage commitment of mesenchymal progenitor cells is still poorly understood.
      Here we demonstrate that Wnt signaling by osteoblasts is essential for
      mesenchymal progenitor cells to differentiate away from a default adipogenic into
      an osteoblastic lineage. Dominant adipogenesis and reduced osteoblastogenesis
      were observed in calvarial cell cultures from transgenic mice characterized by
      osteoblast-targeted disruption of glucocorticoid signaling. This phenotypic shift
      in mesenchymal progenitor cell commitment was associated with reciprocal
      regulation of early adipogenic and osteoblastogenic transcription factors and
      with a reduction in Wnt7b and Wnt10b mRNA and beta-catenin protein levels in
      transgenic versus non-transgenic cultures. Transwell co-culture of transgenic
      mesenchymal progenitor cells with wild type osteoblasts restored commitment to
      the osteoblast lineage. This effect was blocked by adding sFRP1, a Wnt inhibitor,
      to the co-culture. Treatment of transgenic cultures with Wnt3a resulted in
      stimulation of osteoblastogenesis and suppression of adipogenesis. Our findings
      suggest a novel cellular mechanism in bone cell biology in which osteoblasts
      exert direct control over the lineage commitment of their mesenchymal progenitor
      through Wnt signaling. This glucocorticoid-dependent forward control function
      indicates a central role for osteoblasts in the regulation of early
      osteoblastogenesis.

PMID- 18045883
TI  - Interleukin-15 increases vaccine efficacy through a mechanism linked to dendritic
      cell maturation and enhanced antibody titers.
AB  - Interleukin-15 (IL-15) is generally considered to sustain T-cell memory and to be
      a growth factor for natural killer cells. Previous data from our laboratory
      demonstrated that IL-15 is also an important factor for developing human
      dendritic cells. For this study, we investigated the effects of IL-15 on antibody
      responses in mice to a recombinant staphylococcal enterotoxin B (SEB) vaccine
      (STEBVax) in a preclinical model of toxic shock syndrome induced by SEB. We
      observed that mouse spleen cells treated with IL-15 in ex vivo culture gained a
      dendritic cell-like phenotype. Administration of IL-15 to mice also resulted in
      an increased number of mature CD11c+ dendritic cells in mouse spleens. A
      significant, IL-15 dose-dependent increase in antigen-specific antibody was
      observed after coadministration with the vaccine and an aluminum-based adjuvant
      (alhydrogel). Furthermore, the coadministration of IL-15 with STEBVax and
      alhydrogel also protected mice from lethal toxic shock above the levels that
      obtained without IL-15. Thus, the vaccine response enhanced by IL-15 appears to
      be mediated by mature dendritic cells and results in prevalent seroconversion to
      Th2-dependent antibodies. This suggests a potential use of IL-15 as an adjuvant
      for antibody-dependent responses to vaccines.

PMID- 18045884
TI  - Evaluation of an indirect immunofluorescence assay for detection of
      immunoglobulin M (IgM) and IgG antibodies against yellow fever virus.
AB  - The first commercial indirect immunofluorescence assay (IFA) using Euroimmun
      Biochip technology was evaluated for the serodiagnosis of immunoglobulin G (IgG)
      and IgM antibodies against yellow fever virus (YFV) and was compared with the
      plaque reduction neutralization test (PRNT), which is currently the gold standard
      test for YFV. An overall correlation between the tests of 98.7% was established
      based on the analysis of 150 sera from individuals after vaccination with the 17D
      yellow fever vaccine. The sensitivity and specificity, calculated using the 150
      sera from vaccinees and 150 sera from healthy blood donors, were 95% and 95%,
      respectively, for the IgG IFA and 94% and 97% for the IgM IFA. Antibody titers
      found in the PRNT correlated poorly with the IgM and IgG titers detected by IFA.
      The analysis of preexisting heterologous flaviviral immunity revealed the
      presence of antibodies reactive with YFV, tick-borne encephalitis virus, West
      Nile virus, Japanese encephalitis virus, and dengue virus serotypes 1 to 4 in 20
      out of the 150 vaccinees. The indirect IFA showed that nine of these individuals
      with previous flaviviral exposure who received 17D vaccine failed to produce
      detectable IgM antibodies. Despite this preexisting immunity, all vaccinees
      developed protective immunity as detected by PRNT and anti-YFV IgG antibodies as
      detected by IFA. The high specificity and sensitivity of the IFA make it a useful
      tool for rapid diagnosis of yellow fever during outbreaks, for epidemiological
      studies, and for serosurveillance after vaccination.

PMID- 18045885
TI  - Curcumin reduces burn progression in rats.
AB  - OBJECTIVES: Cutaneous burns are dynamic injuries with a central zone of necrosis
      surrounded by a zone of ischemia. Conversion of this ischemic zone to full
      necrosis over the days following injury is due in part to highly reactive oxygen
      radicals. Curcumin is a component of the Oriental spice turmeric that has been
      shown to have antioxidant and antiapoptotic properties. The authors hypothesized
      that treatment of burns with curcumin would reduce the conversion of the ischemic
      zone to full necrosis. METHODS: This was a randomized controlled experiment.
      Twenty Sprague-Dawley rats were used. Two burns were created on each animal's
      dorsum using a brass comb with four rectangular prongs preheated in boiling water
      and applied for 30 seconds, resulting in four rectangular 10 x 20-mm full
      thickness burns separated by three 5 x 20-mm unburned interspaces (zone of
      ischemia). Animals were randomized to curcumin or vehicle by oral gavage 30
      minutes before injury and at 24, 48, and 72 hours after injury. Wounds were
      observed at one, two, and three days after injury for visual evidence of necrosis
      in the unburned interspaces. Full-thickness biopsy specimens from the interspaces
      were evaluated with hematoxylin and eosin staining seven days after injury for
      evidence of necrosis. The percentage of interspaces that progressed to necrosis
      was compared with chi-square tests. RESULTS: Forty comb burns with 120 unburned
      interspaces were created, evenly distributed between curcumin and vehicle alone.
      The percentage of interspaces that progressed to full-thickness necrosis at one,
      two, three, and seven days after injury in the curcumin and vehicle groups were
      30% versus 63% (p = 0.003), 30% versus 70% (p < 0.001), 63% versus 95% (p =
      0.02), and 63% versus 95% (p = 0.02), respectively. CONCLUSIONS: Pretreatment of
      rats with oral curcumin followed by once-daily oral treatment for three days
      reduced the percentage of unburned skin interspaces that progressed to full
      necrosis.

PMID- 18045886
TI  - An alcohol oxidase dipstick rapidly detects methanol in the serum of mice.
AB  - BACKGROUND: Patients presenting with ingestions of methanol and ethylene glycol
      pose a significant challenge to emergency physicians. The decision to initiate
      antidotal therapy must be made quickly and is currently based on the presence of
      indirect signs, symptoms, and laboratory tests, because no real-time diagnostic
      test exists to measure these substances. OBJECTIVES: To determine whether a
      commercially available ethanol-in-saliva detecting dipstick (ALCO-Screen) would
      be a reliable and rapid indicator of toxic alcohol presence in the serum of an
      animal model. METHODS: Fifty mice randomly received intraperitoneal doses of
      methanol, ethylene glycol, or ethanol to induce serum concentrations of
      approximately 5-400 mg/dL. Thirty minutes after injection, serum was obtained.
      Serum was both applied to the dipstick and frozen for definitive concentration
      determination by gas chromatography. After 2 minutes, dipsticks were evaluated
      for color change by a blinded observer and photographed to be evaluated by other
      blinded observers at a later time. RESULTS: All concentrations of methanol > or
      =5 mg/dL consistently caused a color change on the ALCO-Screen. Ethylene glycol
      reliably caused a color change at > or =300 mg/dL. There was significant
      agreement among multiple observers whether or not color change had occurred using
      the ALCO-Screen. CONCLUSIONS: A commercially available dipstick that uses an
      alcohol oxidase colorimetric reaction reliably and rapidly detects very low serum
      concentrations of methanol but not ethylene glycol in this animal model. This
      color change is easily detected by most observers.

PMID- 18045887
TI  - End-tidal carbon dioxide measurements in children with acute asthma.
AB  - OBJECTIVES: A noninvasive method to assess ventilation may aid in management of
      children with acute asthma. The purpose of this study was to evaluate the
      association between end-tidal carbon dioxide (EtCO2) values and disease severity
      among children with acute asthma. METHODS: This was a prospective, blinded,
      observational study of children 3-17 years old treated for acute asthma in a
      pediatric emergency department (ED). EtCO2 measurements were taken before the
      initiation of therapy and after each nebulization treatment (maximum of three).
      Peak expiratory flow rate (PEFR), Pediatric Asthma Severity Score (PASS), oxygen
      saturation, and disposition were recorded. Treating physicians, unaware of the
      EtCO2 results, made all treatment decisions, including disposition. RESULTS: One
      hundred children were enrolled. The mean initial EtCO2 value was 35 mm Hg (95%
      confidence interval = 34.3 to 36.1 mm Hg). The mean disposition EtCO2 value was
      33.3 mm Hg (95% confidence interval = 32.6 to 34.4 mm Hg). PEFR measures were
      completed on 43 patients and PASS recorded on 100 patients. There was an overall
      trend toward lower EtCO2 values during treatment (p < 0.01). Sixteen patients
      were admitted. Initial EtCO2 values were lower among children admitted to the
      hospital (35.6 mm Hg vs. 32.9 mm Hg; Mann-Whitney U test; p < 0.02). EtCO2 values
      at disposition did not differ between groups based on PEFR, PASS, or hospital
      admission. CONCLUSIONS: Noninvasive bedside measurement of EtCO2 values among
      children with acute asthma is feasible. EtCO2 values did not distinguish children
      with mild disease from those with more severe disease. Further data are needed to
      clarify the association between EtCO2 values and other indicators of disease
      severity, particularly in children with more severe disease.

PMID- 18045888
TI  - Multiple encounter simulation for high-acuity multipatient environment training.
AB  - Patient safety interventions for multitasking, multipatient, error-prone work
      settings such as the emergency department (ED) must improve assorted clinical
      abilities, specific cognitive strategies, and teamwork functions of the staff to
      be effective. Multiple encounter simulation scenarios explore and convey this
      specialized mental work-set through use of multiple high-fidelity medical
      simulation (SIM) manikins in realistic surroundings. Multipatient scenarios
      reflect the work situations being targeted yet have the benefit of scripted
      control and instructor guidance to advance specific educational objectives. The
      use of two or more SIM patients promotes the exploration not only of multiple
      distinct clinical issues but also of interdependent processes pervasive in EDs.
      Cascading shortages of time, personnel, equipment, and supplies are re-created,
      thereby replicating process limitations at various levels, in a safe environment
      in which compensatory actions and adaptive behaviors can be learned.
      Distinguishing features of multipatient exercises include 1) broadened
      educational scope and expanded indications for SIM application, 2) enhanced
      scenario complexity, 3) controlled exposure to high workload environments, 4)
      expanded communication requirements, and 5) increased potential for reflective
      learning. Widespread and effective training in well-replicated, carefully
      coordinated representations of complex multipatient work environments may
      strengthen educational interventions for personnel working in high acuity and
      work-overloaded settings such as the ED. The use of concurrent patient encounter
      SIM exercises to elicit calculated stressors and to foster compensatory staff
      behaviors is an educational advance toward this objective. The authors present
      SIM methodology using concurrent patient encounters to replicate these
      environments.

PMID- 18045889
TI  - Development and implementation of a model to improve identification of patients
      infected with HIV using diagnostic rapid testing in the emergency department.
AB  - OBJECTIVES: Infection with the human immunodeficiency virus (HIV) continues to
      expand in nontraditional risk groups, and the prevalence of undiagnosed infection
      remains relatively high in the patient populations of urban emergency departments
      (EDs). Unfortunately, HIV testing in this setting remains uncommon. The
      objectives of this study were 1) to develop a physician-based diagnostic rapid
      HIV testing model, 2) to implement this model in a high-volume urban ED, and 3)
      to prospectively characterize the patients who were targeted by physicians for
      testing and determine the proportions who completed rapid HIV counseling,
      testing, and referral; tested positive for HIV infection; and were successfully
      linked into medical and preventative care. METHODS: An interdisciplinary group of
      investigators developed a model for performing physician-based diagnostic rapid
      HIV testing in the ED. This model was then evaluated using a prospective cohort
      study design. Emergency physicians identified patients at risk for undiagnosed
      HIV infection using clinical judgment and consensus guidelines. Testing was
      performed by the hospital's central laboratory, and clinical social workers
      performed pretest and posttest counseling and provided appropriate medical and
      preventative care referrals, as defined by the model. RESULTS: Over the 30-month
      study period, 105,856 patients were evaluated in the ED. Of these, 681 (0.64%;
      95% confidence interval [CI] = 0.60% to 0.69%) were identified by physicians and
      completed rapid HIV counseling, testing, and referral. Of the 681 patients, 15
      (2.2%; 95% CI = 1.2% to 3.6%) patients tested positive for HIV infection and 12
      (80%; 95% CI = 52% to 96%) were successfully linked into care. CONCLUSIONS: A
      physician-based diagnostic HIV testing model was developed, successfully
      implemented, and sustained in a high-volume, urban ED setting. While the use of
      this model successfully identified patients with undiagnosed HIV infection in the
      ED, the overall level of testing remained low. Innovative testing programs, such
      as nontargeted screening, more specific targeted screening, or alternative hybrid
      methods, are needed to more effectively identify undiagnosed HIV infection in the
      ED patient population.

PMID- 18045890
TI  - Emergency echocardiography.

PMID- 18045891
TI  - Emergency department use of intravenous procainamide for patients with acute
      atrial fibrillation or flutter.
AB  - OBJECTIVES: Acute atrial fibrillation and flutter are very common arrhythmias
      seen in emergency department (ED) patients, but there is no consensus for their
      optimal management. The objective of this study was to examine the efficacy and
      safety of intravenous (IV) procainamide for acute atrial fibrillation or flutter.
      METHODS: This health records review included a consecutive cohort of ED patients
      with acute-onset atrial fibrillation or atrial flutter who received IV
      procainamide at one university hospital ED during a five-year period. The
      standard clinical protocol involved IV infusion of 1 g of procainamide over 60
      minutes, followed by electrical cardioversion if necessary. A trained observer
      extracted data from the original clinical records. Outcome measurements included
      conversion to sinus rhythm, adverse events, and relapse up to seven days.
      RESULTS: The 341 study patients had a mean age of 63.9 years (SD +/- 15.5 years),
      and 56.6% were male. The conversion rates were 52.2% (95% confidence interval =
      47% to 58%) for 316 atrial fibrillation cases and 28.0% (95% confidence interval
      = 13% to 46%) for 25 atrial flutter cases. Mean dose given was 860.7 mg (SD +/-
      231.2 mg), and median time to conversion was 55 minutes. Adverse events occurred
      in 34 cases (10.0%): hypotension, 8.5%; bradycardia, 0.6%; atrioventricular
      block, 0.6%; and ventricular tachycardia, 0.3%. There were no cases of torsades
      de pointes, cerebrovascular accident, or death. Most patients (94.4%) were
      discharged home, but 2.9% of patients returned with a recurrence of atrial
      fibrillation within seven days. CONCLUSIONS: This study of acute atrial
      fibrillation or flutter patients treated in the ED with IV procainamide suggests
      that this treatment is safe and effective in this setting. Procainamide should be
      prospectively compared with other ED strategies.

PMID- 18045892
TI  - A Bayesian sensitivity analysis of out-of-hospital 12-lead electrocardiograms:
      implications for regionalization of cardiac care.
AB  - BACKGROUND: The effectiveness of out-of-hospital regionalization of ST-elevation
      myocardial infarction (STEMI) patients to hospitals providing primary
      percutaneous coronary intervention depends on the accuracy of the out-of-hospital
      12-lead electrocardiogram (PHTL). Although estimates of sensitivity and
      specificity of PHTL for STEMI have been reported, the impact of out-of-hospital
      STEMI prevalence on positive predictive value (PPV) has not been evaluated.
      OBJECTIVES: To describe the relationship between varying population STEMI
      prevalences and PHTL predictive values, using ranges of PHTL sensitivity and
      specificity. METHODS: The authors performed a Bayesian analysis using PHTL, where
      values for sensitivities (60%-70%), specificities (98%), and two prevalence
      ranges (0.5%-5% and 5%-20%) were derived from a literature review. PPV prediction
      intervals were compared with three months of prospective data from the Los
      Angeles County Emergency Medical Services Agency STEMI regionalization program.
      RESULTS: When the estimated prevalence of STEMI in the out-of-hospital population
      is 5%-20%, the median PPV of the PHTL is 83% (95% credible interval [CrI] = 53%
      to 97%). However, if the population prevalence of STEMI is between 0.5% and 5%,
      the median PPV is 43% (95% CrI = 12% to 86%). When the PPV prediction intervals
      were incorporated with the Los Angeles County Emergency Medical Services Agency
      data, the PPV was 66%. CONCLUSIONS: Even when assuming high specificity for PHTL,
      the false-positive rate will be considerable if applied to a population at low
      risk for STEMI. Before broadening application of PHTL to low-risk patients, the
      implications of a high false-positive rate should be considered.

PMID- 18045893
TI  - National trends in emergency department antibiotic prescribing for children with
      acute otitis media, 1996 2005.
AB  - OBJECTIVES: Withholding antibiotics in nontoxic children with acute otitis media
      (AOM) is now recommended to reduce bacterial resistance rates. Using the National
      Hospital Ambulatory Medical Care Survey (NHAMCS), the authors describe the
      national trends for prescribing antibiotics in children with AOM presenting to
      emergency departments (EDs) in the United States over the past decade. The
      authors hypothesized that the rates of prescribing antibiotics would decline over
      time. METHODS: This was a retrospective study of NHAMCS databases. A national
      sampling of ED visits for 1996-2005 was used to identify trends in ED
      prescription of antibiotics to patients with AOM. The National Drug Code
      Directory Drug Classes were used to identify type of antibiotic prescribed.
      Frequency and type of antibiotic prescription patterns over time were evaluated.
      RESULTS: There were 2.6 million and 2.1 million ED visits for AOM during the
      first and last years of the study. Children ages 2-12 years accounted for about
      40% of all ED visits for AOM, with another 40% in the younger than 2 years age
      group and 20% in the older than 12 years of age group. During the first and last
      year of the study, 79.2% and 91.3% of the patients with AOM were prescribed
      antibiotics, respectively. There was a slight increasing trend in the proportion
      prescribed antibiotics over time (p = 0.02). The rates of use of antibiotics for
      AOM were similar in all three age groups. CONCLUSIONS: There was a slight
      increase in the percentage of children with AOM who were prescribed antibiotics
      in the ED between 1996 and 2005. There was also no change in the patterns of
      prescribing antibiotics.

PMID- 18045894
TI  - ED crowding is associated with variable perceptions of care compromise.
AB  - OBJECTIVES: The authors measured the association between emergency department
      (ED) crowding and patient and provider perceptions about whether patient care was
      compromised. METHODS: This was a cross-sectional study of patients admitted from
      the ED and their providers. Surveys of patients, nurses, and resident physicians
      were linked. The primary outcome was agreement or strong agreement on a five-item
      scale assessing whether ED crowding compromised care. Logistic regression was
      used to determine the association between the primary outcome and measures of ED
      crowding. RESULTS: Of 741 patients approached, 644 patients consented (87%); 703
      resident physician surveys (95%) and 716 nursing surveys (97%) were completed. A
      total of 106 patients (16%), 86 residents (12%), and 173 nurses (24%) reported
      that care was compromised by ED crowding. In 252 cases (35%), one or more
      respondents reported that care was compromised. There was poor agreement over
      whose care was compromised. For patients, independent predictors of compromised
      care were waiting room time (odds ratio [OR], 1.05 for each additional 10-minute
      wait [95% confidence interval {CI} = 1.02 to 1.09]) and being surveyed in a
      hallway bed (OR, 2.02 [95% CI = 1.12 to 3.68]). Predictors of compromised care
      for nurses included waiting room time (OR, 1.05 for each additional 10-minute
      wait [95% CI = 1.01 to 1.08]), number of patients in the waiting room (OR, 1.05
      for each additional patient waiting [95% CI = 1.02 to 1.07]), and number of
      admitted patients waiting for an inpatient bed (OR, 1.08 for each additional
      patient [95% CI = 1.03 to 1.12]). For residents, predictors of compromised care
      were patient/nurse ratio (OR, 1.39 for a one-unit increase [95% CI = 1.09 to
      1.20]) and number of admitted patients waiting for an inpatient bed (OR, 1.14 for
      each additional patient [95% CI = 1.10 to 1.75]). CONCLUSIONS: ED crowding is
      associated with perceptions of compromised emergency care. There is considerable
      variability among nurses, patients, and resident physicians over which factors
      are associated with compromised care, whose care was compromised, and how care
      was compromised.

PMID- 18045895
TI  - The National Emergency Department Safety Study: study rationale and design.
AB  - The significance of medical errors is widely appreciated. Given the frequency and
      significance of errors in medicine, it is important to learn how to reduce their
      frequency; however, the identification of factors that increase the likelihood of
      errors poses a considerable challenge. The National Emergency Department Safety
      Study (NEDSS) sought to characterize organizational- and clinician-associated
      factors related to the likelihood of errors occurring in emergency departments
      (EDs). NEDSS was a large multicenter study coordinated by the Emergency Medicine
      Network (EMNet; www.emnet-usa.org). It was designed to determine if reports by ED
      personnel about safety processes are significantly correlated with the actual
      occurrence of errors in EDs. If so, staff reports can be used to accurately
      identify processes for safety improvements. Staff perceptions were assessed with
      a survey, while errors were assessed through chart review of three conditions:
      acute myocardial infarction, acute asthma, and reductions of dislocations under
      procedural sedation. NEDSS also examined the characteristics of EDs associated
      with the occurrence of errors. NEDSS is the first comprehensive national study of
      the frequency and types of medical errors in EDs. This article describes the
      methods used to develop and implement the study.

PMID- 18045896
TI  - International emergency medicine: a review of the literature from 2006.
AB  - The field of international emergency medicine (IEM) has grown rapidly over the
      past several decades, with a rise in the number of IEM fellowship positions,
      sustained growth in the international sections of major emergency medicine
      organizations, and an increase in the range of topics included under its rubric.
      One of the greatest obstacles to the continued growth of IEM remains the lack of
      a high-quality, consolidated, and easily accessible evidence base of literature.
      In response to this perceived need, members of the Emergency Medicine Residents'
      Association IEM Committee, in conjunction with members of the Society for
      Academic Emergency Medicine International Health Interest Group, embarked on the
      task of creating a recurring review of IEM literature. This article reviews 25
      IEM research articles published in 2006. Research articles were selected for the
      review according to explicit, predetermined criteria that included both
      methodological quality and perceived impact of the research. It is the authors'
      hope that this annual review will act as a forum for disseminating best practices
      while also stimulating further research in the field of IEM.

PMID- 18045897
TI  - Gender trends in emergency medicine publications.
AB  - BACKGROUND: In recent years, the number of women entering the field of emergency
      medicine (EM) has increased. OBJECTIVES: To determine if authorship in EM
      publications has increased in parallel with this trend. METHODS: The gender of
      first and last authors of EM articles in Academic Emergency Medicine, American
      Journal of Emergency Medicine, Annals of Emergency Medicine, and Journal of
      Emergency Medicine were examined. The authors reviewed articles from 1985, 1995,
      and 2005 for American Journal of Emergency Medicine, Annals of Emergency
      Medicine, and Journal of Emergency Medicine and from 1999 and 2005 for Academic
      Emergency Medicine. The primary outcomes were the proportions of female authors.
      RESULTS: A total of 2,016 articles were reviewed. Overall, 18% of first and last
      authors were female. Respectively, for 1985, 1995, 1999, and 2005, the
      proportions of female first authors were 9%, 15%, 19%, and 24%; the proportions
      of female last authors were 9%, 18%, 19%, and 22%. The trend of increases in
      female authorship was statistically significant. CONCLUSIONS: Although female
      authorship remains a minority in EM publications, it has increased significantly
      in parallel with increases in female participation in EM.

PMID- 18045898
TI  - Turning on the spotlight: do attention and luminance contrast affect neuronal
      responses in the same way?

PMID- 18045899
TI  - A computational model for redundant human three-dimensional pointing movements:
      integration of independent spatial and temporal motor plans simplifies movement
      dynamics.
AB  - Few computational models have addressed the spatiotemporal features of
      unconstrained three-dimensional (3D) arm motion. Empirical observations made on
      hand paths, speed profiles, and arm postures during point-to-point movements led
      to the assumption that hand path and arm posture are independent of movement
      speed, suggesting that the geometric and temporal properties of movements are
      decoupled. In this study, we present a computational model of 3D movements for an
      arm with four degrees of freedom based on the assumption that optimization
      principles are separately applied at the geometric and temporal levels of
      control. Geometric properties (path and posture) are defined in terms of geodesic
      paths with respect to the kinetic energy metric in the Riemannian configuration
      space. Accordingly, a geodesic path can be generated with less muscular effort
      than on any other, nongeodesic path, because the sum of all configuration-speed
      dependent torques vanishes. The temporal properties of the movement (speed) are
      determined in task space by minimizing the squared jerk along the selected end
      effector path. The integration of both planning levels into a single
      spatiotemporal representation simplifies the control of arm dynamics along
      geodesic paths and results in movements with near minimal torque change and
      minimal peak value of kinetic energy. Thus, the application of Riemannian
      geometry allows for a reconciliation of computational models previously proposed
      for the description of arm movements. We suggest that geodesics are an emergent
      property of the motor system through the exploration of dynamical space. Our data
      validated the predictions for joint trajectories, hand paths, final postures,
      speed profiles, and driving torques.

PMID- 18045900
TI  - Bradykinin-induced microglial migration mediated by B1-bradykinin receptors
      depends on Ca2+ influx via reverse-mode activity of the Na+/Ca2+ exchanger.
AB  - Bradykinin (BK) is produced and acts at the site of injury and inflammation. In
      the CNS, migration of microglia toward the lesion site plays an important role
      pathologically. In the present study, we investigated the effect of BK on
      microglial migration. Increased motility of cultured microglia was mimicked by B1
      receptor agonists and markedly inhibited by a B1 antagonist but not by a B2
      receptor antagonist. BK induced chemotaxis in microglia isolated from wild-type
      and B2-knock-out mice but not from B1-knock-out mice. BK-induced motility was not
      blocked by pertussis toxin but was blocked by chelating intracellular Ca2+ or by
      low extracellular Ca2+, implying that Ca2+ influx is prerequisite. Blocking the
      reverse mode of Na+/Ca2+ exchanger (NCX) completely inhibited BK-induced
      migration. The involvement of NCX was further confirmed by using NCX+/- mice; B1
      agonist-induced motility and chemotaxis was decreased compared with that in
      NCX+/+ mice. Activation of NCX seemed to be dependent on protein kinase C and
      phosphoinositide 3-kinase, and resultant activation of intermediate-conductance
      (IK-type) Ca2+-dependent K+ currents (I(K(Ca))) was activated. Despite these
      effects, BK did not activate microglia, as judged from OX6 staining. Using in
      vivo lesion models and pharmacological injection to the brain, it was shown that
      microglial accumulation around the lesion was also dependent on B1 receptors and
      I(K(Ca)). These observations support the view that BK functions as a
      chemoattractant by using the distinct signal pathways in the brain and, thus,
      attracts microglia to the lesion site in vivo.

PMID- 18045901
TI  - Human cortical activity during streaming without spectral cues suggests a general
      neural substrate for auditory stream segregation.
AB  - The brain continuously disentangles competing sounds, such as two people
      speaking, and assigns them to distinct streams. Neural mechanisms have been
      proposed for streaming based on gross spectral differences between sounds, but
      not for streaming based on other nonspectral features. Here, human listeners were
      presented with sequences of harmonic complex tones that had identical spectral
      envelopes, and unresolved spectral fine structure, but one of two fundamental
      frequencies (f0) and pitches. As the f0 difference between tones increased,
      listeners perceived the tones as being segregated into two streams (one stream
      for each f0) and cortical activity measured with functional magnetic resonance
      imaging and magnetoencephalography increased. This trend was seen in primary
      cortex of Heschl's gyrus and in surrounding nonprimary areas. The results
      strongly resemble those for pure tones. Both the present and pure tone results
      may reflect neuronal forward suppression that diminishes as one or more features
      of successive sounds become increasingly different. We hypothesize that feature
      specific forward suppression subserves streaming based on diverse perceptual cues
      and results in explicit neural representations for auditory streams within
      auditory cortex.

PMID- 18045902
TI  - EEG-informed fMRI reveals spatiotemporal characteristics of perceptual decision
      making.
AB  - Single-unit and multiunit recordings in primates have already established that
      decision making involves at least two general stages of neural processing:
      representation of evidence from early sensory areas and accumulation of evidence
      to a decision threshold from decision-related regions. However, the relay of
      information from early sensory to decision areas, such that the accumulation
      process is instigated, is not well understood. Using a cued paradigm and single
      trial analysis of electroencephalography (EEG), we previously reported on
      temporally specific components related to perceptual decision making. Here, we
      use information derived from our previous EEG recordings to inform the analysis
      of fMRI data collected for the same behavioral task to ascertain the cortical
      origins of each of these EEG components. We demonstrate that a cascade of events
      associated with perceptual decision making takes place in a highly distributed
      neural network. Of particular importance is an activation in the lateral
      occipital complex implicating perceptual persistence as a mechanism by which
      object decision making in the human brain is instigated.

PMID- 18045903
TI  - Enhanced accumulation of phosphorylated alpha-synuclein and elevated beta-amyloid
      42/40 ratio caused by expression of the presenilin-1 deltaT440 mutant associated
      with familial Lewy body disease and variant Alzheimer's disease.
AB  - Mutations in the PSEN1 gene encoding presenilin 1 (PS1) are linked to a vast
      majority of pedigrees with early-onset, autosomal dominant forms of familial
      Alzheimer's disease (FAD). Lewy body (LB) pathology is frequently found in the
      brains of FAD patients harboring PSEN1 mutations. We recently reported on a novel
      PS1 mutation with the deletion of threonine at codon 440 (deltaT440) in a
      familial case diagnosed as having the neocortical type of dementia with LBs (DLB)
      and variant AD. In this report, we investigated the possible involvement of PS1
      deltaT440 mutation in aberrant alpha-synuclein accumulation. We established cell
      lines that stably express either wild-type (WT) PS1 or the FAD-linked PS1 H163R,
      E280A, deltaE9, and PS1 deltaT440 mutants and now demonstrate that the expression
      of the PS1 deltaT440 mutant led to a marked elevation in the ratio of beta
      amyloid (Abeta) 42/40 peptides in a conditioned medium. More importantly, we
      report here that the levels of phosphorylated alpha-synuclein increase in
      neuronal and non-neuronal cells expressing the PS1 deltaT440 mutant compared with
      cells that express WT PS1 or the PS1 H163R and E280A variants that are not
      associated with LB pathology. This finding is consistent with our demonstration
      of elevated levels of phosphorylated alpha-synuclein in the detergent-resistant
      fraction prepared from a patient's brain with PS1 deltaT440 mutation. These
      observations raise the intriguing suggestion that the mechanism(s) by which the
      PS1 deltaT440 mutant causes DLB and variant AD are by enhancing the
      phosphorylation of alpha-synuclein and the ratio of Abeta(42/40) peptides,
      respectively, in the brain.

PMID- 18045904
TI  - Polarity-regulating kinase partitioning-defective 1/microtubule affinity
      regulating kinase 2 negatively regulates development of dendrites on hippocampal
      neurons.
AB  - Neurons are highly polarized cells that possess two morphologically and
      functionally different types of protrusions, axons and dendrites, that function
      in the transmission and reception of neural signals, respectively. A great deal
      of attention has been paid to the specification and guidance of axons, but the
      mechanism of dendrite development remains mostly unknown. We report here that a
      polarity-regulating kinase, partitioning-defective 1 (Par1b)/microtubule affinity
      regulating kinase 2 (MARK2), specifically regulates development of dendrites in
      hippocampal neurons. Ectopic expression of Par1b/MARK2 shortens the length and
      decreases branching of dendrites without significant effects on axons. Knockdown
      of endogenous Par1b/MARK2 by RNA interference stimulates dendrite development.
      Wnt stimulation and Dishevelled expression, both of which are known to induce
      dendrite development, induced recruitment of Par1b/MARK2 to the membrane
      fraction. Expression of a Par1b/MARK2 mutant, that contains a myristoylation
      signal and accumulates exclusively in membranes, does not affect dendrite
      development. In addition, Par1b/MARK2 efficiently phosphorylated MAP2, which is
      localized mainly in dendrites. These results indicate that Par1b/MARK2 negatively
      regulates dendrite development through phosphorylation of MAP2.

PMID- 18045905
TI  - The TLC: a novel auditory nucleus of the mammalian brain.
AB  - We have identified a novel nucleus of the mammalian brain and termed it the
      tectal longitudinal column (TLC). Basic histologic stains, tract-tracing
      techniques and three-dimensional reconstructions reveal that the rat TLC is a
      narrow, elongated structure spanning the midbrain tectum longitudinally. This
      paired nucleus is located close to the midline, immediately dorsal to the
      periaqueductal gray matter. It occupies what has traditionally been considered
      the most medial region of the deep superior colliculus and the most medial region
      of the inferior colliculus. The TLC differs from the neighboring nuclei of the
      superior and inferior colliculi and the periaqueductal gray by its distinct
      connections and cytoarchitecture. Extracellular electrophysiological recordings
      show that TLC neurons respond to auditory stimuli with physiologic properties
      that differ from those of neurons in the inferior or superior colliculi. We have
      identified the TLC in rodents, lagomorphs, carnivores, nonhuman primates, and
      humans, which indicates that the nucleus is conserved across mammals. The
      discovery of the TLC reveals an unexpected level of longitudinal organization in
      the mammalian tectum and raises questions as to the participation of this
      mesencephalic region in essential, yet completely unexplored, aspects of
      multisensory and/or sensorimotor integration.

PMID- 18045906
TI  - Cdc42 regulates cofilin during the establishment of neuronal polarity.
AB  - The establishment of polarity is an essential process in early neuronal
      development. Although a number of molecules controlling neuronal polarity have
      been identified, genetic evidence about their physiological roles in this process
      is mostly lacking. We analyzed the consequences of loss of Cdc42, a central
      regulator of polarity in multiple systems, on the polarization of mammalian
      neurons. Genetic ablation of Cdc42 in the brain led to multiple abnormalities,
      including striking defects in the formation of axonal tracts. Neurons from the
      Cdc42 null animals sprouted neurites but had a strongly suppressed ability to
      form axons both in vivo and in culture. This was accompanied by disrupted
      cytoskeletal organization, enlargement of the growth cones, and inhibition of
      filopodial dynamics. Axon formation in the knock-out neurons was rescued by
      manipulation of the actin cytoskeleton, indicating that the effects of Cdc42
      ablation are exerted through modulation of actin dynamics. In addition, the knock
      outs showed a specific increase in the phosphorylation (inactivation) of the
      Cdc42 effector cofilin. Furthermore, the active, nonphosphorylated form of
      cofilin was enriched in the axonal growth cones of wild-type, but not of mutant,
      neurons. Importantly, cofilin knockdown resulted in polarity defects
      quantitatively analogous to the ones seen after Cdc42 ablation. We conclude that
      Cdc42 is a key regulator of axon specification, and that cofilin is a
      physiological downstream effector of Cdc42 in this process.

PMID- 18045907
TI  - Glial cell migration in the eye disc.
AB  - Any complex nervous system is made out of two major cell types, neurons and glial
      cells. A hallmark of glial cells is their pronounced ability to migrate. En route
      to their final destinations, glial cells are generally guided by neuronal
      signals. Here we show that in the developing visual system of Drosophila glial
      cell migration is largely controlled by glial-glial interactions and occurs
      independently of axonal contact. Differentiation into wrapping glia is initiated
      close to the morphogenetic furrow. Using single cell labeling experiments we
      identified six distinct glial cell types in the eye disc. The migratory glial
      population is separated from the wrapping glial cells by the so-called carpet
      cells, extraordinary large glial cells, each covering a surface area of
      approximately 10,000 epithelial cells. Subsequent cell ablation experiments
      demonstrate that the carpet glia regulates glial migration in the eye disc
      epithelium and suggest a new model underlying glial migration and differentiation
      in the developing visual system.

PMID- 18045909
TI  - Differential effects of serotonin and dopamine on human 5-HT3A receptor kinetics:
      interpretation within an allosteric kinetic model.
AB  - Serotonin type 3 (5-HT3) receptors are members of the pentameric Cys-loop
      superfamily of receptors that modulate synaptic neurotransmission. In response to
      agonist binding and unbinding, members of this superfamily undergo a series of
      conformational transitions that define their functional properties. In this
      study, we report the results of electrophysiological studies using rapid solution
      exchange designed to characterize and compare the actions of the high-efficacy
      agonist serotonin and the low-efficacy agonist dopamine on human 5-HT3A receptors
      expressed in human embryonic kidney HEK293 cells. In the case of serotonin,
      receptor activation rates varied with agonist concentration, and deactivation
      occurred as a single-exponential process with a rate that was similar to the
      maximal rate of desensitization. Receptors recovered slowly from long
      desensitizing pulses of serotonin with a sigmoidal time course. In the case of
      dopamine, receptor activation rates were independent of agonist concentration,
      receptor deactivation occurred as a complex process that was significantly faster
      than the maximal rate of desensitization, and recovery from desensitization
      occurred more quickly than with 5-HT and its time course was not sigmoidal. We
      developed an allosteric kinetic model for 5-HT3A receptor activation,
      deactivation, desensitization, and resensitization. Interpretation of our results
      within the context of this model indicated that the distinct modulatory actions
      of serotonin versus dopamine are largely attributable to the vastly different
      rates with which these two agonists induce channel opening and dissociate from
      open and desensitized states.

PMID- 18045908
TI  - Lack of self-administration of cocaine in dopamine D1 receptor knock-out mice.
AB  - Evidence suggests a critical role for dopamine in the reinforcing effects of
      cocaine in rats and primates. However, self-administration has been less often
      studied in the mouse species, and, to date, "knock-out" of individual dopamine
      related genes in mice has not been reported to reduce the reinforcing effects of
      cocaine. We studied the dopamine D1 receptor and cocaine self-administration in
      mice using a combination of gene-targeted mutation and pharmacological tools. Two
      cohorts with varied breeding and experimental histories were tested, and, in both
      cohorts, there was a significant decrease in the number of D1 receptor knock-out
      mice that met criteria for acquisition of cocaine self-administration (2 of 23)
      relative to wild-type mice (27 of 32). After extinction of responding with saline
      self-administration, dose-response studies showed that cocaine reliably and dose
      dependently maintained responding greater than saline in all wild-type mice but
      in none of the D1 receptor knock-out mice. The D1-like agonist SKF 82958
      (2,3,4,5,-tetrahydro-6-chloro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
      hydrobromide) and the D2-like agonist quinelorane both functioned as positive
      reinforcers in wild-type mice but not in D1 receptor mutant mice, whereas food
      and intravenous injections of the opioid agonist remifentanil functioned as
      positive reinforcers in both genotypes. Finally, pretreatment with the D1-like
      antagonist SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3
      benzazepine-7-01] produced surmountable antagonism of the reinforcing effects of
      cocaine in the commonly used strain C57BL/6J. We conclude that D1 receptor knock
      out mice do not reliably self-administer cocaine and that the D1 receptor is
      critical for the reinforcing effects of cocaine and other dopamine agonists, but
      not food or opioids, in mice.

PMID- 18045910
TI  - The Down syndrome critical region protein RCAN1 regulates long-term potentiation
      and memory via inhibition of phosphatase signaling.
AB  - Regulator of calcineurin 1 (RCAN1/MCIP1/DSCR1) regulates the calmodulin-dependent
      phosphatase calcineurin. Because it is located on human chromosome 21, RCAN1 has
      been postulated to contribute to mental retardation in Down syndrome and has been
      reported to be associated with neuronal degeneration in Alzheimer's disease. The
      studies herein are the first to assess the role of RCAN1 in memory and synaptic
      plasticity by examining the behavioral and electrophysiological properties of
      RCAN1 knock-out mice. These mice exhibit deficits in spatial learning and memory,
      reduced associative cued memory, and impaired late-phase long-term potentiation
      (L-LTP), phenotypes similar to those of transgenic mice with increased
      calcineurin activity. Consistent with this, the RCAN1 knock-out mice display
      increased enzymatic calcineurin activity, increased abundance of a cleaved
      calcineurin fragment, and decreased phosphorylation of the calcineurin substrate
      dopamine and cAMP-regulated phosphoprotein-32. We propose a model in which RCAN1
      plays a positive role in L-LTP and memory by constraining phosphatase signaling.

PMID- 18045911
TI  - Exogenous delivery of heat shock protein 70 increases lifespan in a mouse model
      of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder
      that results in the progressive loss of motoneurons (MNs) in the CNS. Several
      survival and death mechanisms of MNs have been characterized and it has been
      determined that MNs do not appear to mount a complete stress response, as
      determined by the lack of heat shock protein 70 (Hsp70) upregulation after
      several stress paradigms. Hsp70 has been shown to confer neuroprotection and the
      insufficient availability of Hsp70 may contribute to MNs' susceptibility to death
      in ALS mice. In this study, recombinant human Hsp70 (rhHsp70) was
      intraperitoneally injected three times weekly, beginning at postnatal day 50
      until endstage, to G93A mutant SOD1 (G93A SOD1) mice. The administration of
      rhHsp70 was effective at increasing lifespan, delaying symptom onset, preserving
      motor function and prolonging MN survival. Interestingly, injected rhHsp70
      localized to skeletal muscle and was not readily detected in the CNS. Treatment
      with rhHsp70 also resulted in an increased number of innervated neuromuscular
      junctions compared with control tissue. Together these results suggest rhHsp70
      may delay disease progression in the G93A SOD1 mouse via a yet to be identified
      peripheral mechanism.

PMID- 18045912
TI  - Metabotropic glutamate receptor 5 modulates nociceptive plasticity via
      extracellular signal-regulated kinase-Kv4.2 signaling in spinal cord dorsal horn
      neurons.
AB  - Metabotropic glutamate receptors (mGluRs) play important roles in the modulation
      of nociception. The group I mGluRs (mGlu1 and mGlu5) modulate nociceptive
      plasticity via activation of extracellular signal-regulated kinase (ERK)
      signaling. We reported recently that the K+ channel Kv4.2 subunit underlies A
      type K+ currents in the spinal cord dorsal horn and is modulated by the ERK
      signaling pathway. Kv4.2-mediated A-type currents are important determinants of
      dorsal horn neuronal excitability and central sensitization that underlies
      hypersensitivity after tissue injury. In the present study, we demonstrate that
      ERK-mediated phosphorylation of Kv4.2 is downstream of mGlu5 activation in spinal
      cord dorsal horn neurons. Activation of group I mGluRs inhibited Kv4.2-mediated A
      type K+ currents and increased neuronal excitability in dorsal horn neurons.
      These effects were mediated by activation of mGlu5, but not mGlu1, and were
      dependent on ERK activation. Analysis of Kv4.2 phosphorylation site mutants
      clearly identified S616 as the residue responsible for mGlu5-ERK-dependent
      modulation of A-type currents and excitability. Furthermore, nociceptive behavior
      induced by activation of spinal group I mGluRs was impaired in Kv4.2 knock-out
      mice, demonstrating that, in vivo, modulation of Kv4.2 is downstream of mGlu5
      activation. Altogether, our results indicate that activation of mGlu5 leads to
      ERK-mediated phosphorylation and modulation of Kv4.2-containing potassium
      channels in dorsal horn neurons. This modulation may contribute to nociceptive
      plasticity and central sensitization associated with chronic inflammatory pain
      conditions.

PMID- 18045913
TI  - Dopaminergic modulation of spinal neuronal excitability.
AB  - It is well recognized that dopamine (DA) can modulate spinal networks and
      reflexes. DA fibers and receptors are present in the spinal cord, and evidence
      for DA release within the spinal cord has been published. A critical gap is the
      lack of data regarding dopaminergic modulation of intrinsic and synaptic
      properties of motoneurons and ventral interneurons in the mammalian spinal cord.
      In this paper, we address this issue by examining the cellular mechanisms
      underlying the excitatory effect of DA on motor systems. We examine the effects
      of DA on two classes of cells important for motor control, motoneurons and Hb9
      interneurons, located in lamina VIII. We show that DA can boost excitability in
      spinal motoneurons by decreasing the first spike latency and the
      afterhyperpolarization. Collectively, this leads to an increase in the frequency
      current slope likely attributable to modulation of I(A) and SK(Ca) (small
      conductance calcium-activated K+ channel) currents. We also demonstrate that DA
      increases glutamatergic transmission onto motoneurons. Our data also suggest that
      DA stabilizes the rhythmic output of conditionally bursting interneurons.
      Collectively, these data indicate that DA has widespread actions on intrinsic and
      synaptic properties of ventral spinal neurons.

PMID- 18045914
TI  - Spatial attention does not strongly modulate neuronal responses in early human
      visual cortex.
AB  - Attention can dramatically enhance behavioral performance based on a visual
      stimulus, but the degree to which attention modulates activity in early visual
      cortex is unclear. Whereas single-unit studies of spatial attention in monkeys
      have repeatedly revealed relatively modest attentional modulations in V1, human
      functional magnetic resonance imaging studies demonstrate a large attentional
      enhancement of the blood oxygen level-dependent (BOLD) signal in V1. To explore
      this discrepancy, we used intracranial electrodes to directly measure the effect
      of spatial attention on the responses of neurons near the human occipital pole.
      We found that spatial attention does not robustly modulate stimulus-driven local
      field potentials in early human visual cortex, but instead produces modest
      modulations that are consistent with those seen in monkey neurophysiology
      experiments. This finding suggests that the neuronal activity that underlies
      visual attention in humans is similar to that found in other primates and that
      behavioral state may alter the linear relationship between neuronal activity and
      BOLD.

PMID- 18045915
TI  - NMDA receptor activation dephosphorylates AMPA receptor glutamate receptor 1
      subunits at threonine 840.
AB  - Phosphorylation-dependent changes in AMPA receptor function have a crucial role
      in activity-dependent forms of synaptic plasticity such as long-term potentiation
      (LTP) and long-term depression (LTD). Although three previously identified
      phosphorylation sites in AMPA receptor glutamate receptor 1 (GluR1) subunits
      (S818, S831, and S845) appear to have important roles in LTP and LTD, little is
      known about the role of other putative phosphorylation sites in GluR1. Here, we
      describe the characterization of a recently identified phosphorylation site in
      GluR1 at threonine 840. The results of in vivo and in vitro phosphorylation
      assays suggest that T840 is not a substrate for protein kinases known to
      phosphorylate GluR1 at previously identified phosphorylation sites, such as
      protein kinase A, protein kinase C, and calcium/calmodulin-dependent kinase II.
      Instead, in vitro phosphorylation assays suggest that T840 is a substrate for
      p70S6 kinase. Although LTP-inducing patterns of synaptic stimulation had no
      effect on GluR1 phosphorylation at T840 in the hippocampal CA1 region, bath
      application of NMDA induced a strong, protein phosphatase 1- and/or 2A-mediated
      decrease in T840 phosphorylation. Moreover, GluR1 phosphorylation at T840 was
      transiently decreased by a chemical LTD induction protocol that induced a short
      term depression of synaptic strength and persistently decreased by a chemical LTD
      induction protocol that induced a lasting depression of synaptic transmission.
      Together, our results show that GluR1 phosphorylation at T840 is regulated by
      NMDA receptor activation and suggest that decreases in GluR1 phosphorylation at
      T840 may have a role in LTD.

PMID- 18045916
TI  - Sensitization of pain-modulating neurons in the rostral ventromedial medulla
      after peripheral nerve injury.
AB  - Nerve injury can lead to mechanical hypersensitivity in both humans and animal
      models, such that innocuous touch produces pain. Recent functional studies have
      demonstrated a critical role for descending pain-facilitating influences from the
      rostral ventromedial medulla (RVM) in neuropathic pain, but the underlying
      mechanisms and properties of the relevant neurons within the RVM are essentially
      unknown. We therefore characterized mechanical responsiveness of physiologically
      characterized neurons in the RVM after spinal nerve ligation, a model of
      neuropathic pain that produces robust mechanical hyperalgesia and allodynia. RVM
      neurons were studied 7-14 d after spinal nerve ligation, and classified as "on
      cells," "off-cells," or "neutral cells" using standard criteria of changes in
      firing associated with heat-evoked reflexes. On-cells are known to promote
      nociception, and off-cells to suppress nociception, whereas the role of neutral
      cells in pain modulation remains an open question. Neuronal and behavioral
      responses to innocuous and noxious mechanical stimulation were tested using
      calibrated von Frey filaments (4-100 g) applied to the hindpaws ipsilateral and
      contralateral to the injury, and in sham-operated and unoperated control animals.
      On- and off-cells recorded in nerve-injured animals exhibited novel responses to
      innocuous mechanical stimulation, and enhanced responses to noxious mechanical
      stimulation. Neuronal hypersensitivity in the RVM was correlated with behavioral
      hypersensitivity. Neutral cells remained unresponsive to cutaneous stimulation
      after nerve injury. These data demonstrate that both on- and off-cells in the RVM
      are sensitized to innocuous and noxious mechanical stimuli after nerve injury.
      This sensitization likely contributes to allodynia and hyperalgesia of
      neuropathic pain states.

PMID- 18045917
TI  - Magnocellular projections as the trigger of top-down facilitation in recognition.
AB  - Object recognition is traditionally viewed as a hierarchical, bottom-up neural
      process. This view has been challenged recently by theoretical models and by
      findings indicating that top-down processes are involved in facilitating
      recognition. However, how such high-level information can be activated quickly
      enough to facilitate the bottom-up processing is yet unknown. We propose that
      such top-down facilitation is triggered by magnocellular information projected
      early and rapidly to the orbitofrontal cortex. Using human neuroimaging, we show
      that stimuli designed to bias processing toward the magnocellular pathway
      differentially activated the orbitofrontal cortex compared with parvocellular
      biased stimuli. Although the magnocellular stimuli had a lower contrast than the
      parvocellular stimuli, they were recognized faster and just as accurately.
      Moreover, orbitofrontal activity predicted the performance advantage for the
      magnocellular, but not for the parvocellular-biased, stimuli, whereas the
      opposite was true in the fusiform gyrus. Last, analyses of effective connectivity
      using dynamic causal modeling showed that magnocellular-biased stimuli
      significantly activated pathways from occipital visual cortex to orbitofrontal
      cortex and from orbitofrontal cortex to fusiform gyrus. Conversely, parvocellular
      biased stimuli significantly activated a pathway from the occipital visual cortex
      to fusiform gyrus. Our findings support the proposal that fast magnocellular
      projections linking early visual and inferotemporal object recognition regions
      with the orbitofrontal cortex facilitate object recognition by enabling the
      generation of early predictions.

PMID- 18045918
TI  - Congruent activity during action and action observation in motor cortex.
AB  - A variety of studies have shown that motor cortical areas can be activated by
      observation of familiar actions. Here, we describe single-neuron responses in
      monkey primary motor (MI) and dorsal premotor (PMd) cortices during passive
      observation and execution of a familiar task. We show that the spiking
      modulation, preferred directions, and encoded information of cells in MI and PMd
      remain consistent during both observation and movement. Furthermore, we find that
      the presence of a visual target is necessary to elicit this congruent neural
      activity during observation. These findings along with results from our analysis
      of the oscillatory power in the beta frequency of the local field potential are
      consistent with previous imaging and EEG studies that have suggested that
      congruence between observation and action is a general feature of the motor
      system, even outside of canonical "mirror" areas. Such congruent activity has
      proposed relevance to motor learning, mimicry, and communication and has
      practical applications for the development of motor-cortical neuroprostheses in
      paralyzed patients.

PMID- 18045919
TI  - Modulation of acid-sensing ion channel activity by nitric oxide.
AB  - Acid-sensing ion channels (ASICs) are a class of ion channels activated by
      extracellular protons and are believed to mediate the pain caused by tissue
      acidosis. Although ASICs have been widely studied, little is known about their
      regulation by inflammatory mediators. Here, we provide evidence that nitric oxide
      (NO) potentiates the activity of ASICs. Whole-cell patch-clamp recordings were
      performed on neonatal rat cultured dorsal root ganglion neurons and on ASIC
      isoforms expressed in CHO cells. The NO donor S-nitroso-N-acetylpenicillamine
      (SNAP) potentiates proton-gated currents in DRG neurons and proton-gated currents
      in CHO cells expressing each of the acid-sensitive ASIC subunits. Modulators of
      the cGMP/PKG pathway had no effect on the potentiation, but in excised patches
      from CHO cells expressing ASIC2a, the potentiation could be reversed by
      externally applied reducing agents. NO therefore has a direct external effect on
      the ASIC ion channel, probably through oxidization of cysteine residues.
      Complementary psychophysiological studies were performed using iontophoresis of
      acidic solutions through the skin of human volunteers. Topical application of the
      NO donor glyceryl trinitrate significantly increased acid-evoked pain but did not
      affect heat or mechanical pain thresholds. ASICs may therefore play an important
      role in the pain associated with metabolic stress and inflammation, where both
      tissue acidosis and a high level of NO are present.

PMID- 18045920
TI  - Spatial properties and functional organization of small bistratified ganglion
      cells in primate retina.
AB  - The primate visual system consists of parallel pathways initiated by distinct
      cell types in the retina that encode different features of the visual scene.
      Small bistratified cells (SBCs), which form a major projection to the thalamus,
      exhibit blue-ON/yellow-OFF [S-ON/(L+M)-OFF] light responses thought to be
      important for high-acuity color vision. However, the spatial processing
      properties of individual SBCs and their spatial arrangement across the visual
      field are poorly understood. The present study of peripheral primate retina
      reveals that contrary to previous suggestions, SBCs exhibit center-surround
      spatial structure, with the (L+M)-OFF component of the receptive field
      approximately 50% larger in diameter than the S-ON component. Analysis of
      response kinetics shows that the (L+M)-OFF response in SBCs is slower than the S
      ON response and significantly less transient than that of simultaneously recorded
      OFF-parasol cells. The (L+M)-OFF response in SBCs was eliminated by bath
      application of the metabotropic glutamate receptor agonist L-APB. These
      observations indicate that the (L+M)-OFF response of SBCs is not formed by OFF
      bipolar cell input as has been suspected and suggest that it arises from
      horizontal cell feedback. Finally, the receptive fields of SBCs form orderly
      mosaics, with overlap and regularity similar to those of ON-parasol cells. Thus,
      despite their distinctive morphology and chromatic properties, SBCs exhibit two
      features of other retinal ganglion cell types: center-surround antagonism and
      regular mosaic sampling of visual space.

PMID- 18045921
TI  - Characterization of the role of microtubule-associated protein 1B in metabotropic
      glutamate receptor-mediated endocytosis of AMPA receptors in hippocampus.
AB  - The mGluR-dependent endocytosis of AMPA receptors (AMPARs) in the CA1 region is
      protein synthesis dependent. However, why this form of trafficking, and not that
      mediated by NMDA receptor activation, is dependent on protein translation is
      unclear. Here we have studied the contribution of the cytoskeletal microtubule
      associated protein 1B (MAP1B) to the pathway-specific internalization of AMPARs.
      Treatments of cultured neurons with 3,4-dihydroxyphenylglycol (DHPG) or NMDA,
      both of which drive AMPAR endocytosis, caused a translation-dependent increase in
      the dendritic levels of MAP1B protein. Although interfering with protein
      synthesis using short interfering RNA (siRNA) to eEF2 kinase (eukaryotic
      elongation factor 2 kinase) blocked the dendritic MAP1B increase by both
      pathways, it selectively blocked the DHPG- and not the NMDA-induced AMPAR
      endocytosis. In support of MAP1B synthesis contributing to metabotropic glutamate
      receptor (mGluR)-mediated AMPAR endocytosis, siRNA against MAP1B in CA1 cultured
      neurons specifically blocked the DHPG-induced AMPAR internalization. Previous
      studies suggest a direct interaction between MAP1B and the AMPAR-binding protein
      GRIP1. Biochemical studies establish that MAP1B associates with GRIP1 and forms a
      complex with GluR2 in vivo in rat hippocampus. Furthermore, the interaction
      between MAP1B and GRIP1 increased significantly in acute slices after treatment
      with DHPG and not NMDA. Together, these findings suggest that MAP1B plays a
      selective role in the DHPG-induced endocytosis of AMPARs, perhaps through its
      interaction with GRIP1.

PMID- 18045922
TI  - Top-down control of multimodal sensitivity in the barn owl optic tectum.
AB  - We studied the effects of electrically microstimulating a gaze-control area in
      the owl's forebrain, the arcopallial gaze fields (AGFs), on the responsiveness of
      neurons in the optic tectum (OT) to visual and auditory stimuli. Microstimulation
      of the AGF enhanced the visual and auditory responsiveness and stimulus
      discriminability of OT neurons representing the same location in space as that
      represented at the microstimulation site in the AGF. At such OT sites, AGF
      microstimulation also sharpened auditory receptive fields and shifted them toward
      the location represented at the AGF stimulation site. At the same time, AGF
      microstimulation suppressed the responsiveness of OT neurons that represented
      visual or auditory stimuli at other locations in space. The top-down influences
      of this forebrain gaze-control area on sensory responsiveness in the owl OT are
      strikingly similar to the space-specific regulation of visual responsiveness in
      the monkey visual cortex produced by voluntary attention as well as by
      microstimulation of the frontal eye fields. This experimental approach provides a
      means for discovering mechanisms that underlie the top-down regulation of sensory
      responses.

PMID- 18045923
TI  - Visceral afferents directly activate catecholamine neurons in the solitary tract
      nucleus.
AB  - Brainstem A2/C2 neurons are catecholamine (CA) neurons within the solitary tract
      nucleus (NTS) that influence many homeostatic functions, including cardiovascular
      reflexes, food intake, and stress. Because NTS is a major interface between
      sensory visceral afferents and the CNS, NTS CA neurons are ideally suited to
      coordinate complex responses by their projections to multiple brain regions. To
      test how NTS CA neurons process visceral afferent information carried by solitary
      tract (ST) afferents, we identified CA neurons using transgenic mice expressing
      TH-EGFP (enhanced green fluorescent protein under the control of the tyrosine
      hydroxylase promoter) and recorded synaptic responses to ST activation in
      horizontal slices. ST shocks evoked large-amplitude, short-latency, glutamatergic
      EPSCs (ST-EPSCs) in 90% of NTS CA neurons. Within neurons, ST-EPSCs had constant
      latency, rarely failed, and depressed substantially at high ST frequencies,
      indicating that NTS CA neurons receive direct monosynaptic connections from
      afferent terminals. NTS CA neurons received direct ST inputs from only one or two
      afferent fibers, with one-half also receiving smaller amplitude indirect inputs.
      Up to 90% of ST shocks evoked action potentials in NTS CA neurons. However,
      transmission of sensory afferent information through NTS CA neurons critically
      depended on the expression of an A-type potassium current (I(KA)), which when
      active attenuated ST-activated action potentials to a 37% success rate. The
      satiety peptide, cholecystokinin, presynaptically facilitated glutamate
      transmission in one-half of NTS CA neurons. Thus, NTS CA neurons are directly
      driven by visceral afferents with output being modulated by presynaptic peptide
      receptors and postsynaptic potassium channels.

PMID- 18045924
TI  - Is the prefrontal cortex necessary for establishing cognitive sets?
AB  - There is evidence from neuroimaging that the prefrontal cortex may be involved in
      establishing task set activity in advance of presentation of the task itself. To
      find out whether it plays an essential role, we examined patients with unilateral
      lesions of the rostral prefrontal cortex. They were first instructed as to
      whether to perform a spatial or a verbal working memory task and then given
      spatial and verbal items after a delay of 4-12 s. The patients showed an increase
      in switch costs, making more errors by repeating what they had done on the
      previous trial. They were able to establish regional task set activity during the
      instruction delay, as evidenced by sustained changes in the blood oxygenation
      level-dependent signal in caudal frontal regions. However, in contrast to healthy
      controls, they were less able to maintain functional connectivity among the
      surviving task-related brain regions, as evidenced by reduced correlations
      between them during instruction delays. The results suggest that the left rostral
      prefrontal cortex is indeed required for establishing a cognitive set but that
      the essential function is to support the functional connectivity among the task
      related regions.

PMID- 18045925
TI  - Functional compartmentalization of endosomal trafficking for the synaptic
      delivery of AMPA receptors during long-term potentiation.
AB  - Endosomal membrane trafficking in dendritic spines is important for proper
      synaptic function and plasticity. However, little is known about the molecular
      identity and functional compartmentalization of the membrane trafficking
      machinery operating at the postsynaptic terminal. Here we report that the
      transport of AMPA-type glutamate receptors into synapses occurs in two discrete
      steps, and we identify the specific endosomal functions that control this process
      during long-term potentiation. We found that Rab11-dependent endosomes
      translocate AMPA receptors from the dendritic shaft into spines. Subsequently, an
      additional endosomal trafficking step, controlled by Rab8, drives receptor
      insertion into the synaptic membrane. Separate from this receptor delivery route,
      we show that Rab4 mediates a constitutive endosomal recycling within the spine.
      This Rab4-dependent cycling is critical for maintaining spine size but does not
      influence receptor transport. Therefore, our data reveal a highly
      compartmentalized endosomal network within the spine and identify the molecular
      components and functional organization of the membrane organelles that mediate
      AMPA receptor synaptic delivery during plasticity.

PMID- 18045926
TI  - Spatial organization of neuronal population responses in layer 2/3 of rat barrel
      cortex.
AB  - Individual pyramidal neurons of neocortex show sparse and variable responses to
      sensory stimuli in vivo. It has remained unclear how this variability extends to
      population responses on a trial-to-trial basis. Here, we characterized single
      neuron and population responses to whisker stimulation in layer 2/3 (L2/3) of
      identified columns in rat barrel cortex using in vivo two-photon calcium imaging.
      Optical detection of single action potentials from evoked calcium transients
      revealed low spontaneous firing rates (0.25 Hz), variable response probabilities
      (range, 0-0.5; mean, 0.2 inside barrel column), and weak angular tuning of L2/3
      neurons. On average, both the single-neuron response probability and the
      percentage of the local population activated were higher in the barrel column
      than above septa or in neighboring columns. Within the barrel column, mean
      response probability was highest in the center (0.4) and declined toward the
      barrel border. Neuronal pairs showed correlations in both spontaneous and sensory
      evoked activity that depended on the location of the neurons. Correlation
      decreased with increasing distance between neurons and, for neuronal pairs the
      same distance apart, with distance of the pair from the barrel column center.
      Although neurons are therefore not activated independently from each other, we
      did not observe precisely repeating spatial activation patterns. Instead,
      population responses showed large trial-to-trial variability. Nevertheless, the
      accuracy of decoding stimulus onset times from local population activity
      increased with population size and depended on anatomical location. We conclude
      that, despite their sparseness and variability, L2/3 population responses show a
      clear spatial organization on the columnar scale.

PMID- 18045928
TI  - Activity-dependent ubiquitination of GABA(A) receptors regulates their
      accumulation at synaptic sites.
AB  - GABA(A) receptors (GABA(A)Rs) are the major mediators of fast synaptic inhibition
      in the brain. In neurons, these receptors undergo significant rates of
      endocytosis and exocytosis, processes that regulate both their accumulation at
      synaptic sites and the efficacy of synaptic inhibition. Here we have evaluated
      the role that neuronal activity plays in regulating the residence time of
      GABA(A)Rs on the plasma membrane and their targeting to synapses. Chronic
      blockade of neuronal activity dramatically increases the level of the GABA(A)R
      ubiquitination, decreasing their cell surface stability via a mechanism dependent
      on the activity of the proteasome. Coincident with this loss of cell surface
      expression levels, TTX treatment reduced both the amplitude and frequency of
      miniature inhibitory synaptic currents. Conversely, increasing the level of
      neuronal activity decreases GABA(A)R ubiquitination enhancing their stability on
      the plasma membrane. Activity-dependent ubiquitination primarily acts to reduce
      GABA(A)R stability within the endoplasmic reticulum and, thereby, their insertion
      into the plasma membrane and subsequent accumulation at synaptic sites. Thus,
      activity-dependent ubiquitination of GABA(A)Rs and their subsequent proteasomal
      degradation may represent a potent mechanism to regulate the efficacy of synaptic
      inhibition and may also contribute to homeostatic synaptic plasticity.

PMID- 18045927
TI  - Gene expression profiling in postmortem prefrontal cortex of major depressive
      disorder.
AB  - Investigations of the molecular mechanisms underlying major depressive disorder
      (MDD) have been hampered by the complexity of brain tissue and sensitivity of
      gene expression profiling approaches. To address these issues, we used discrete
      microdissections of postmortem dorsolateral prefrontal cortex (DLPFC) (area 9)
      and an oligonucleotide (60mer) microarray hybridization procedure that increases
      sensitivity without RNA amplification. Mixed-effects statistical methods were
      used to rigorously control for medication usage in the subset of medicated
      depressed subjects. These analyses yielded a rich profile of dysregulated genes.
      Two of the most highly dysregulated genes of interest were stresscopin, a
      neuropeptide involved in stress responses, and Forkhead box D3 (FOXD3), a
      transcription factor. Secondary cell-based analysis demonstrated that stresscopin
      and FoxD3 are increased in neurons of DLPFC gray matter of MDD subjects. These
      findings identify abnormal gene expression in a discrete region of MDD subjects
      and contribute to further elucidation of the molecular alterations of this
      complex mood disorder.

PMID- 18045929
TI  - Opposing regulation of pair bond formation by cAMP signaling within the nucleus
      accumbens shell.
AB  - The formation of monogamous pair bonds, by prairie voles, is facilitated by
      activation of dopamine (DA) D2-like, but not D1-like, receptors within the
      nucleus accumbens (NAcc) shell. Because DA exerts opposing regulation of cAMP
      production depending on the subtype of receptor activated, we tested the
      hypothesis that DA regulation of pair bond formation is mediated via the cAMP
      signaling cascade. Consistent with activation of D2-like receptors, decreasing
      cAMP signaling, by blocking cAMP binding sites on protein kinase A (PKA),
      facilitated partner preference formation. Conversely, increasing cAMP signaling,
      by preventing the activation of inhibitory G-proteins, activating stimulatory G
      proteins, or stimulating PKA prevented the formation of mating-induced partner
      preferences. These manipulations were effective in the shell, but not the core,
      of the NAcc. Together, these data demonstrate opposing regulation over pair bond
      formation by cAMP signaling within the NAcc shell.

PMID- 18045930
TI  - Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg
      AD mice.
AB  - Estrogen depletion in postmenopausal women is a significant risk factor for the
      development of Alzheimer's disease (AD), and estrogen-based hormone therapy may
      reduce this risk. However, the effects of progesterone both alone and in
      combination with estrogen on AD neuropathology remain unknown. In this study, we
      used the triple transgenic mouse model of AD (3xTg-AD) to investigate the
      individual and combined effects of estrogen and progesterone on beta-amyloid
      (Abeta) accumulation, tau hyperphosphorylation, and hippocampal-dependent
      behavioral impairments. In gonadally intact female 3xTg-AD mice, AD-like
      neuropathology was apparent by 3 months of age and progressively increased
      through age 12 months, a time course that was paralleled by behavioral
      impairment. Ovariectomy-induced depletion of sex steroid hormones in adult female
      3xTg-AD mice significantly increased Abeta accumulation and worsened memory
      performance. Treatment of ovariectomized 3xTg-AD mice with estrogen, but not
      progesterone, prevented these effects. When estrogen and progesterone were
      administered in combination, progesterone blocked the beneficial effect of
      estrogen on Abeta accumulation but not on behavioral performance. Interestingly,
      progesterone significantly reduced tau hyperphosphorylation when administered
      both alone and in combination with estrogen. These results demonstrate that
      estrogen and progesterone independently and interactively regulate AD-like
      neuropathology and suggest that an optimized hormone therapy may be useful in
      reducing the risk of AD in postmenopausal women.

PMID- 18045931
TI  - Cell factors stimulate human immunodeficiency virus type 1 reverse transcription
      in vitro.
AB  - After fusion of the human immunodeficiency virus type 1 (HIV-1) envelope with the
      host cell membrane, the HIV-1 core enters the cell cytoplasm. Core components are
      then restructured to form the reverse transcription complex (RTC); the
      biochemical details of this process are currently unclear. To investigate early
      RTC formation, we characterized the endogenous reverse transcription activity of
      virions, which was less efficient than reverse transcription during cell
      infection and suggested a requirement for a cell factor. The addition of
      detergent to virions released reverse transcriptase and capsid, and reverse
      transcription products became susceptible to the action of exogenous nucleases,
      indicating virion disruption. Disruption was coincident with the loss of the
      endogenous reverse transcription activity of virions, particularly late reverse
      transcription products. Consistent with this observation, the use of a modified
      "spin thru" method, which uses brief detergent exposure, also disrupted virions.
      The addition of lysates made from mammalian cell lines (Jurkat, HEK293T, and NIH
      3T3 cells) to virions delipidated by detergent stimulated late reverse
      transcription efficiency. A complex with reverse transcription activity that was
      slower sedimenting than virions on a velocity gradient was greatly stimulated to
      generate full-length reverse transcription products and was associated with only
      relatively small amounts of capsid. These experiments suggest that cell factors
      are required for efficient reverse transcription of HIV-1.

PMID- 18045932
TI  - Foot-and-mouth disease virus forms a highly stable, EDTA-resistant complex with
      its principal receptor, integrin alphavbeta6: implications for infectiousness.
AB  - The initial stage of foot-and-mouth disease virus (FMDV) infection is virus
      binding to cell surface integrins via the RGD motif in the GH loop of the VP1
      capsid protein. As for all ligand/integrin interactions, the initial contact
      between FMDV and its integrin receptors is cation dependent and hence inhibited
      by EDTA. We have investigated this binding process with RGD-containing peptides
      derived from the VP1 capsid protein of FMDV and discovered that, upon binding,
      some of these peptides form highly stable, EDTA-resistant associations with
      integrin alphavbeta6. Peptides containing specific substitutions show that this
      stable binding is dependent on a helical structure immediately C terminal to the
      RGD and, specifically, two leucine residues at positions RGD +1 and RGD +4. These
      observations have a biological consequence, as we show further that stable, EDTA
      resistant binding to alphavbeta6 is a property also exhibited by FMDV particles.
      Thus, the integrin-binding loop of FMDV appears to have evolved to form very
      stable complexes with the principal receptor of FMDV, integrin alphavbeta6. An
      ability to induce such stable complexes with its cellular receptor is likely to
      contribute significantly to the high infectiousness of FMDV.

PMID- 18045933
TI  - Murine endogenous retrovirus MuERV-L is the progenitor of the "orphan" epsilon
      viruslike particles of the early mouse embryo.
AB  - Viruslike particles which displayed a peculiar wheellike appearance that
      distinguished them from A-, B- or C-type particles had previously been described
      in the early mouse embryo. The maximum expression of these so-called epsilon
      particles was observed in two-cell-stage embryos, followed by their rapid decline
      at later stages of development and no particles detected at the zygote one-cell
      stage. Here, we show that these particles are in fact produced by a newly
      discovered murine endogenous retrovirus (ERV) belonging to the widespread family
      of mammalian ERV-L elements and named MuERV-L. Using antibodies that we raised
      against the Gag protein of these elements, Western blot analysis and in toto
      immunofluorescence studies of the embryos at various stages disclosed the same
      developmental expression profile as that observed for epsilon particles. Using
      expression vectors for cloned, full-length, entirely coding MuERV-L copies and
      cell transfection, direct identification of the epsilon particles was finally
      achieved by high-resolution electron microscopy.

PMID- 18045934
TI  - Differential targeting of nuclear pore complex proteins in poliovirus-infected
      cells.
AB  - Poliovirus disrupts nucleocytoplasmic trafficking and results in the cleavage of
      two nuclear pore complex (NPC) proteins, Nup153 and Nup62. The NPC is a 125-MDa
      complex composed of multiple copies of 30 different proteins. Here we have
      extended the analysis of the NPC in infected cells by examining the status of
      Nup98, an interferon-induced NPC protein with a major role in mRNA export. Our
      results indicate that Nup98 is targeted for cleavage after infection but that
      this occurs much more rapidly than it does for Nup153 and Nup62. In addition, we
      find that cleavage of these NPC proteins displays differential sensitivity to the
      viral RNA synthesis inhibitor guanidine hydrochloride. Inhibition of nuclear
      import and relocalization of host nuclear proteins to the cytoplasm were only
      apparent at later times after infection when all three nucleoporins (Nups) were
      cleaved. Surprisingly, analysis of the distribution of mRNA in infected cells
      revealed that proteolysis of Nup98 did not result in an inhibition of mRNA
      export. Cleavage of Nup98 could be reconstituted by the addition of purified
      rhinovirus type 2 2A(pro) to whole-cell lysates prepared from uninfected cells,
      suggesting that the 2A protease has a role in this process in vivo. These results
      indicate that poliovirus differentially targets subsets of NPC proteins at early
      and late times postinfection. In addition, targeting of interferon-inducible NPC
      proteins, such as Nup98, may be an additional weapon in the arsenal of poliovirus
      and perhaps other picornaviruses to overcome host defense mechanisms.

PMID- 18045935
TI  - Role of alveolar macrophages in respiratory transmission of visna/maedi virus.
AB  - A major route of transmission of Visna/maedi virus (VMV), an ovine lentivirus, is
      thought to be via the respiratory tract, by inhalation of either cell-free or
      cell-associated virus. In previous studies, we have shown that infection via the
      lower respiratory tract is much more efficient than via upper respiratory tissues
      (T. N. McNeilly, P. Tennant, L. Lujan, M. Perez, and G. D. Harkiss, J. Gen.
      Virol. 88:670-679, 2007). Alveolar macrophages (AMs) are prime candidates for the
      initial uptake of virus in the lower lung, given their in vivo tropism for VMV,
      abundant numbers, location within the airways, and role in VMV-induced
      inflammation. Furthermore, AMs are the most likely cell type involved in the
      transmission of cell-associated virus. In this study, we use an experimental in
      vivo infection model that allowed the infection of specific segments of the ovine
      lung. We demonstrate that resident AMs are capable of VMV uptake in vivo and that
      this infection is associated with a specific up-regulation of AM granulocyte
      macrophage colony-stimulating factor mRNA expression (P < 0.05) and an increase
      in bronchoalveolar lymphocyte numbers (P < 0.05), but not a generalized
      inflammatory response 7 days postinfection. We also demonstrate that both
      autologous and heterologous VMV-infected AMs are capable of transmitting virus
      after lower, but not upper, respiratory tract instillation and that this transfer
      of virus appears not to involve the direct migration of virus-infected AMs from
      the airspace. These results suggest that virus is transferred from AMs into the
      body via an intermediate route. The results also suggest that the inhalation of
      infected AMs represents an additional mechanism of virus transmission.

PMID- 18045936
TI  - Establishment of canine RNA polymerase I-driven reverse genetics for influenza A
      virus: its application for H5N1 vaccine production.
AB  - In the event of a new influenza pandemic, vaccines whose antigenicities match
      those of circulating strains must be rapidly produced. Here, we established an
      alternative reverse genetics system for influenza virus using the canine
      polymerase I (PolI) promoter sequence that works efficiently in the Madin-Darby
      canine kidney cell line, a cell line approved for human vaccine production. Using
      this system, we were able to generate H5N1 vaccine seed viruses more efficiently
      than can be achieved with the current system that uses the human PolI promoter in
      African green monkey Vero cells, thus improving pandemic vaccine production.

PMID- 18045937
TI  - Infectious bronchitis viruses with a novel genomic organization.
AB  - A number of novel infectious bronchitis viruses (IBVs) were previously identified
      in commercial poultry in Australia, where they caused significant economic
      losses. Since there has been only limited characterization of these viruses, we
      investigated the genomic and phenotypic differences between these novel IBVs and
      other, classical IBVs. The 3' 7.5 kb of the genomes of 17 Australian IBV strains
      were sequenced, and growth properties of 6 of the strains were compared.
      Comparison of sequences of the genes coding for structural and nonstructural
      proteins revealed the existence of two IBV genotypes: classical and novel. The
      genomic organization of the classical IBVs was typical of those of other group
      III coronaviruses: 5'-Pol-S-3a-3b-E-M-5a-5b-N-untranslated region (UTR)-3'.
      However, the novel IBV genotype lacked either all or most of the genes coding for
      nonstructural proteins at the 3' end of the genome and had a unique open reading
      frame, X1. The gene order was either 5'-Pol-S-X1-E-M-N-UTR-3' or 5'-Pol-S-X1-E-M
      5b-N-UTR-3'. Phenotypically, novel and classical IBVs also differed; novel IBVs
      grew at a slower rate and reached lower titers in vitro and in vivo and were
      markedly less immunogenic in chicks. Although the novel IBVs induced
      histopathological lesions in the tracheas of infected chicks that were comparable
      to those induced by classical strains, they did not induce lesions in the
      kidneys. This study has demonstrated for the first time the existence of a
      naturally occurring IBV genotype devoid of some of the genes coding for
      nonstructural proteins and has also indicated that all of the accessory genes are
      dispensable for the growth of IBV and that such viruses are able to cause
      clinical disease and economic loss. The phylogenic differences between these
      novel IBVs and other avian coronaviruses suggest a reservoir host distinct from
      domestic poultry.

PMID- 18045939
TI  - Increased levels of galactose-deficient anti-Gal immunoglobulin G in the sera of
      hepatitis C virus-infected individuals with fibrosis and cirrhosis.
AB  - Hepatitis B and C viruses are major causative agents of liver fibrosis,
      cirrhosis, and liver cancer. Using comparative glycoproteomics, we identified a
      glycoprotein that is altered both in amount and in glycosylation as a function of
      liver fibrosis and cirrhosis. Specifically, this altered glycoprotein is an
      immunoglobulin G (IgG) molecule reactive to the heterophilic alpha-Gal epitope
      [Galalpha-1-3Galbeta1-(3)4GlcNAc-R]. While similar changes in glycosylation have
      been observed in several autoimmune diseases, the specific immunoglobulins and
      their antigen recognition profiles were not determined. Thus, we provide the
      first report identifying the specific antigenic recognition profile of an
      immunoglobulin molecule containing altered glycosylation as a function of liver
      disease. This change in glycosylation allowed increased reactivity with several
      fucose binding lectins and permitted the development of a plate-based assay to
      measure this change. Increased lectin reactivity was observed in 100% of the more
      than 200 individuals with stage III or greater fibrosis and appeared to be
      correlated with the degree of fibrosis. The reason for the alteration in the
      glycosylation of anti-Gal IgG is currently unclear but may be related to the
      natural history of the disease and may be useful in the noninvasive detection of
      fibrosis and cirrhosis.

PMID- 18045938
TI  - Integrin alphaVbeta3 Binds to the RGD motif of glycoprotein B of Kaposi's sarcoma
      associated herpesvirus and functions as an RGD-dependent entry receptor.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) envelope-associated glycoprotein B
      (gB) is involved in the initial steps of binding to host cells during KSHV
      infection. gB contains an RGD motif reported to bind the integrin alpha(3)beta(1)
      during virus entry. Although the ligand specificity of alpha(3)beta(1) has been
      controversial, current literature indicates that alpha(3)beta(1) ligand
      recognition is independent of RGD. We compared alpha(3)beta(1) to the RGD-binding
      integrin, alpha(V)beta(3), for binding to envelope-associated gB and a gB(RGD)
      peptide. Adhesion assays demonstrated that beta(3)-CHO cells overexpressing
      alpha(V)beta(3) specifically bound gB(RGD), whereas alpha(3)-CHO cells
      overexpressing alpha(3)beta(1) did not. Function-blocking antibodies to
      alpha(V)beta(3) inhibited the adhesion of HT1080 fibrosarcoma cells to gB(RGD),
      while antibodies to alpha(3)beta(1) did not. Using affinity-purified integrins
      and confocal microscopy, alpha(V)beta(3) bound to gB(RGD) and KSHV virions,
      demonstrating direct receptor-ligand interactions. Specific alpha(V)beta(3)
      antagonists, including cyclic and dicyclic RGD peptides and alpha(V)beta(3)
      function-blocking antibodies, inhibited KSHV infection by 70 to 80%.
      Keratinocytes from alpha(3)-null mice lacking alpha(3)beta(1) were fully
      competent for infection by KSHV, and reconstitution of alpha(3)beta(1) function
      by transfection with alpha(3) cDNA reduced KSHV infectivity from 74% to 55%.
      Additional inhibitory effects of alpha(3)beta(1) on the cell surface expression
      of alpha(V)beta(3) and on alpha(V)beta(3)-mediated adhesion of alpha(3)-CHO cells
      overexpressing alpha(3)beta(1) were detected, consistent with previous reports of
      transdominant inhibition of alpha(V)beta(3) function by alpha(3)beta(1). These
      observations may explain previous reports of an inhibition of KSHV infection by
      soluble alpha(3)beta(1). Our studies demonstrate that alpha(V)beta(3) is a
      cellular receptor mediating both the cell adhesion and entry of KSHV into target
      cells through binding the virion-associated gB(RGD).

PMID- 18045940
TI  - Spontaneous recovery in acute human hepatitis C virus infection: functional T
      cell thresholds and relative importance of CD4 help.
AB  - The mechanisms mediating protective immunity to hepatitis C virus (HCV) infection
      are incompletely understood because early infection in humans is rarely
      identified, particularly in those individuals who subsequently demonstrate
      spontaneous virus eradication. We have established a large national network of
      patients with acute HCV infection. Here, we comprehensively examined total HCV
      specific CD4(+) and CD8(+) T-cell responses and identified functional T-cell
      thresholds that predict recovery. Interestingly, we found that the presence of
      HCV-specific cytotoxic T lymphocytes (CTLs) that can proliferate, exhibit
      cytotoxicity, and produce gamma interferon does not ensure recovery, but whether
      these CTLs were primed in the presence or absence of CD4(+) T-cell help (HCV
      specific interleukin-2 production) is a critical determinant. These results have
      important implications for early prediction of the virologic outcome following
      acute HCV and for the development of novel immunotherapeutic approaches.

PMID- 18045941
TI  - Adeno-associated virus type 12 (AAV12): a novel AAV serotype with sialic acid-
      and heparan sulfate proteoglycan-independent transduction activity.
AB  - Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy.
      Recent isolations of novel AAV serotypes have led to significant advances by
      broadening the tropism and increasing the efficiency of gene transfer to the
      desired target cell. However, a major concern that remains is the strong
      preexisting immune responses to several vectors. In this paper, we describe the
      isolation and characterization of AAV12, an AAV serotype with unique biological
      and immunological properties. In contrast to those of all other reported AAVs,
      AAV12 cell attachment and transduction do not require cell surface sialic acids
      or heparan sulfate proteoglycans. Furthermore, rAAV12 is resistant to
      neutralization by circulating antibodies from human serum. The feasibility of
      rAAV12 as a vector was demonstrated in a mouse model in which muscle and salivary
      glands were transduced. These characteristics make rAAV12 an interesting
      candidate for gene transfer applications.

PMID- 18045942
TI  - Macrophage-derived simian immunodeficiency virus exhibits enhanced infectivity by
      comparison with T-cell-derived virus.
AB  - Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infect
      and productively replicate in macrophages and T lymphocytes. Here, we show that
      SIV virions derived from macrophages have higher levels of infectivity than those
      derived from T cells. The lower infectivity of T-cell-derived viruses is
      influenced by the quantity or type of mannose residues on the virion. Our results
      demonstrate that the cellular origin of a virus is a major factor in viral
      infectivity. Cell-type-specific factors in viral infectivity, and organ-specific
      or disease stage-specific differences in cellular derivation of virions, can be
      critical in the pathogenesis of HIV and AIDS.

PMID- 18045943
TI  - Evolution to pathogenicity of the parvovirus minute virus of mice in
      immunodeficient mice involves genetic heterogeneity at the capsid domain that
      determines tropism.
AB  - Very little is known about the role that evolutionary dynamics plays in diseases
      caused by mammalian DNA viruses. To address this issue in a natural host model,
      we compared the pathogenesis and genetics of the attenuated fibrotropic and the
      virulent lymphohematotropic strains of the parvovirus minute virus of mice (MVM),
      and of two invasive fibrotropic MVM (MVMp) variants carrying the I362S or K368R
      change in the VP2 major capsid protein, in the infection of severe combined
      immunodeficient (SCID) mice. By 14 to 18 weeks after oronasal inoculation, the
      I362S and K368R viruses caused lethal leukopenia characterized by tissue damage
      and inclusion bodies in hemopoietic organs, a pattern of disease found by 7 weeks
      postinfection with the lymphohematotropic MVM (MVMi) strain. The MVMp populations
      emerging in leukopenic mice showed consensus sequence changes in the MVMi
      genotype at residues G321E and A551V of VP2 in the I362S virus infections or
      A551V and V575A changes in the K368R virus infections, as well as a high level of
      genetic heterogeneity within a capsid domain at the twofold depression where
      these residues lay. Amino acids forming this capsid domain are important MVM
      tropism determinants, as exemplified by the switch in MVMi host range toward
      mouse fibroblasts conferred by coordinated changes of some of these residues and
      by the essential character of glutamate at residue 321 for maintaining MVMi
      tropism toward primary hemopoietic precursors. The few viruses within the
      spectrum of mutants from mice that maintained the respective parental 321G and
      575V residues were infectious in a plaque assay, whereas the viruses with the
      main consensus sequences exhibited low levels of fitness in culture. Consistent
      with this finding, a recombinant MVMp virus carrying the consensus sequence
      mutations arising in the K368R virus background in mice failed to initiate
      infection in cell lines of different tissue origins, even though it caused rapid
      course lethal leukopenia in SCID mice. The parental consensus genotype prevailed
      during leukopenia development, but plaque-forming viruses with the reversion of
      the 575A residue to valine emerged in affected organs. The disease caused by the
      DNA virus in mice, therefore, involves the generation of heterogeneous viral
      populations that may cooperatively interact for the hemopoietic syndrome. The
      evolutionary changes delineate a sector of the surface of the capsid that
      determines tropism and that surrounds the sialic acid receptor binding domain.

PMID- 18045944
TI  - Pathogenesis and immune responses in gnotobiotic calves after infection with the
      genogroup II.4-HS66 strain of human norovirus.
AB  - We previously characterized the pathogenesis of two host-specific bovine enteric
      caliciviruses (BEC), the GIII.2 norovirus (NoV) strain CV186-OH and the
      phylogenetically unassigned NB strain, in gnotobiotic (Gn) calves. In this study
      we evaluated the Gn calf as an alternative animal model to study the pathogenesis
      and host immune responses to the human norovirus (HuNoV) strain GII.4-HS66. The
      HuNoV HS66 strain caused diarrhea (five/five calves) and intestinal lesions
      (one/two calves tested) in the proximal small intestine (duodenum and jejunum) of
      Gn calves, with lesions similar to, but less severe than, those described for the
      Newbury agent 2 (NA-2) and NB BEC. Viral capsid antigen was also detected in the
      jejunum of the proximal small intestine of one of two calves tested by
      immunohistochemistry. All inoculated calves shed virus in feces (five/five
      calves), and one/five had viremia. Antibodies and cytokine (proinflammatory,
      tumor necrosis factor alpha [TNF-alpha]; Th1, interleukin-12 [IL-12] and gamma
      interferon [IFN-gamma]; Th2, IL-4; Th2/T-regulatory, IL-10) profiles were
      determined in serum, feces, and intestinal contents (IC) of the HuNoV-HS66
      inoculated calves (n = 5) and controls (n = 4) by enzyme-linked immunosorbent
      assay in the acute (postinoculation day 3 [PID 3]) and convalescent (PID 28)
      stages of infection. The HuNoV-HS66-specific antibody and cytokine-secreting
      cells (CSCs) were quantitated by ELISPOT in mononuclear cells of local and
      systemic tissues at PID 28. Sixty-seven percent of the HuNoV-HS66-inoculated
      calves seroconverted, and 100% coproconverted with immunoglobulin A (IgA) and/or
      IgG antibodies to HuNoV-HS66, at low titers. The highest numbers of antibody
      secreting cells (ASC), both IgA and IgG, were detected locally in intestine, but
      systemic IgA and IgG ASC responses also occurred in the HuNoV-HS66-inoculated
      calves. In serum, HuNoV-HS66 induced higher peaks of TNF-alpha and IFN-gamma at
      PIDs 2, 7, and 10; of IL-4 and IL-10 at PID 4; and of IL-12 at PIDs 7 and 10,
      compared to controls. In feces, cytokines increased earlier (PID 1) than in serum
      and TNF-alpha and IL-10 were elevated acutely in the IC of the HS66-inoculated
      calves. Compared to controls, at PID 28 higher numbers of IFN-gamma and TNF-alpha
      CSCs were detected in mesenteric lymph nodes (MLN) or spleen and Th2 (IL-4) CSCs
      were elevated in intestine; IL-10 CSCs were highest in spleen. Our study provides
      new data confirming HuNoV-HS66 replication and enteropathogenicity in Gn calves
      and reveals important and comprehensive aspects of the host's local (intestine
      and MLN) and systemic (spleen and blood) immune responses to HuNoV-HS66.

PMID- 18045947
TI  - Pregnancy and the risk of breast cancer.
AB  - It is well established that childless women and women having children later in
      life are at an increased risk of developing breast cancer. In particular, women
      having a first child before 20 years of age have a 50% reduction in lifetime
      breast cancer risk when compared with women who do not have children. This
      protective effect is specific for estrogen receptor positive breast cancer.
      Nevertheless, it remains unclear how parity decreases breast cancer risk.
      Possible mechanisms of action include changes to the hormonal profile of parous
      women, a more differentiated and so less susceptible mammary gland or changes
      within specific epithelial cell subpopulations. In this review, we discuss the
      epidemiological evidence for the protective effects of parity on breast cancer.
      We also explore the mechanisms by which parity protects, with a particular
      emphasis on the role of stem cells and the interactions between stem cells and
      estrogen.

PMID- 18045946
TI  - Gamma/Delta T-cell functional responses differ after pathogenic human
      immunodeficiency virus and nonpathogenic simian immunodeficiency virus
      infections.
AB  - The objective of this study was to functionally assess gamma/delta (gammadelta) T
      cells following pathogenic human immunodeficiency virus (HIV) infection of humans
      and nonpathogenic simian immunodeficiency virus (SIV) infection of sooty
      mangabeys. gammadelta T cells were obtained from peripheral blood samples from
      patients and sooty mangabeys that exhibited either a CD4-healthy (>200 CD4(+) T
      cells/mul blood) or CD4-low (<200 CD4 cells/mul blood) phenotype. Cytokine flow
      cytometry was utilized to assess production of Th1 cytokines tumor necrosis
      factor alpha and gamma interferon following ex vivo stimulation with either
      phorbol myristate acetate/ionomycin or the Vdelta2 gammadelta T-cell receptor
      agonist isopentenyl pyrophosphate. Sooty mangabeys were observed to have higher
      percentages of gammadelta T cells in their peripheral blood than humans did.
      Following stimulation, gammadelta T cells from SIV-positive (SIV(+)) mangabeys
      maintained or increased their ability to express the Th1 cytokines regardless of
      CD4(+) T-cell levels. In contrast, HIV-positive (HIV(+)) patients exhibited a
      decreased percentage of gammadelta T cells expressing Th1 cytokines following
      stimulation. This dysfunction is primarily within the Vdelta2(+) gammadelta T
      cell subset which incurred both a decreased overall level in the blood and a
      reduced Th1 cytokine production. Patients treated with highly active
      antiretroviral therapy exhibited a partial restoration in their gammadelta T-cell
      Th1 cytokine response that was intermediate between the responses of the
      uninfected and HIV(+) patients. The SIV(+) sooty mangabey natural hosts, which do
      not proceed to clinical AIDS, provide evidence that gammadelta T-cell dysfunction
      occurs in HIV(+) patients and may contribute to HIV disease progression.

PMID- 18045945
TI  - Cellular entry of lymphocytic choriomeningitis virus.
AB  - In contrast to most enveloped viruses that enter the host cell via clathrin
      dependent endocytosis, the Old World arenavirus lymphocytic choriomeningitis
      virus (LCMV) enters cells via noncoated vesicles that deliver the virus to
      endosomes, where pH-dependent membrane fusion occurs. Here, we investigated the
      initial steps of LCMV infection. We found that the attachment of LCMV to its
      cellular receptor alpha-dystroglycan occurs rapidly and is not dependent on
      membrane cholesterol. However, subsequent virus internalization is sensitive to
      cholesterol depletion, indicating the involvement of a cholesterol-dependent
      pathway. We provide evidence that LCMV entry involves an endocytotic pathway that
      is independent of clathrin and caveolin and that does not require the GTPase
      dynamin. In addition, neither the structural integrity nor the dynamics of the
      actin cytoskeleton are required for infection. These findings indicate that the
      prototypic Old World arenavirus LCMV uses a mechanism of entry that is different
      from clathrin-mediated endocytosis, which is used by the New World arenavirus
      Junin virus, and pathways used by other enveloped viruses.

PMID- 18045948
TI  - Pheochromocytoma: an update on genetics and management.
AB  - Pheochromocytomas (PHEOs) are rare neoplasms that produce catecholamines and
      usually arise from the adrenal medulla and are considered to be an adrenal
      paraganglioma (PGL). Closely related tumors of extraadrenal sympathetic and
      parasympathetic paraganglia are classified as extraadrenal PGLs. Most PHEOs are
      sporadic, but a significant percentage (approximately 25%) may be found in
      patients with germline mutations of genes predisposing to the development of von
      Hippel-Lindau disease, neurofibromatosis 1, multiple endocrine neoplasia type 1
      (MEN1) and 2 (MEN2), and the PGL/PHEOs syndrome, based on the described mutations
      of the genes for succinate dehydrogenase subunit D (SDHD), B (SDHB), and C
      (SDHC). As one out of four PHEOs turns out to be a hereditary clinical entity,
      screening for genetic alterations is important, as it provides useful information
      for a rational diagnostic approach and management. This review discusses the
      genetics, the pathophysiology of hypertension, the clinical picture, the
      biochemical and imaging diagnosis, and the preferred therapeutic approach for
      PGLs/PHEOs. Furthermore, it emphasizes the need for genetic testing in cases with
      apparently sporadic PHEOs.

PMID- 18045949
TI  - New insights in thyroid follicular cell biology and its impact in thyroid cancer
      therapy.
AB  - Well-differentiated thyroid cancer has in general terms a very good outcome. It
      has a very slow growth rate and, although it metastasizes at a relatively high
      frequency, it has very high survival rates. Whereas the prevalence of nodular
      thyroid disease worldwide is high, malignant conversion from benign thyroid
      nodules is rare. Treatment of thyroid cancer is usually successful, but we still
      do not have effective therapies for patients with invasive or metastatic thyroid
      cancer if the disease does not concentrate radioiodine and it is not surgically
      resectable. On the other hand, from the same thyroid cell, one of the most
      aggressive human tumours can arise--undifferentiated or anaplastic thyroid
      carcinoma--leading to death in a few months. What features of this malignancy
      account for such paradoxical behaviour? The most common type of thyroid cancer-
      papillary thyroid carcinoma--stands out among solid tumours because many of the
      tumour-initiating events have been identified. All of them function in a single
      pathway--the RTK/RAS/RAF/MAPK pathway--and obey an 'exclusivity principle': one
      and only one component of the pathway is mutated in a single tumour. This
      highlights the requirement of this signal transduction pathway for the
      transformation to thyroid cancer and paves the way to targeted therapies against
      a tumour with a mutation in a known gene or any gene upstream of the target.
      However, it is also interesting to underscore the differences among the tumours
      arising from the different mutations. Studies in vitro and in vivo, including
      genomic profiling and genetically engineered mouse models, have clearly shown
      that each oncoprotein exerts its own oncogenic drive, conferring a distinct
      biological behaviour on thyroid tumours. In this review, we attempt to summarise
      the most recent advances in thyroid follicular cell-derived cancers research and
      their potential clinical impact that may change the management of thyroid cancer
      in the near future.

PMID- 18045950
TI  - Non-islet cell tumour-induced hypoglycaemia: a review of the literature including
      two new cases.
AB  - This review focuses on the tumour types and symptoms associated with non-islet
      cell tumour-induced hypoglycaemia (NICTH) as well as the pathogenesis, diagnosis
      and treatment of this rare paraneoplastic phenomenon. In addition, we report two
      illustrative cases of patients suffering from NICTH caused by a solid fibrous
      tumour and a haemangiopericytoma respectively. In the first case, NICTH resolved
      following complete resection of the tumour, but in the second case the patient
      needed long-term treatment aimed at controlling hypoglycaemia because of non
      resectable metastases. Many tumour types have been associated with NICTH. The
      crucial event in the development of NICTH seems to be overexpression of the IGF
      II gene by the tumour. NICTH is characterised by recurrent fasting hypoglycaemia
      and is associated with the secretion of incompletely processed precursors of IGF
      II ('big'-IGF-II) by the tumour. This induces dramatic secondary changes in the
      circulating levels of insulin, GH, IGF-I and IGF-binding proteins, resulting in
      an insulin-like hypoglycaemic activity of 'big'-IGF-II.

PMID- 18045951
TI  - Adiponectin signals in prostate cancer cells through Akt to activate the
      mammalian target of rapamycin pathway.
AB  - Adiponectin has received much attention due to its beneficial effects on insulin
      sensitivity, and epidemiologic studies have further shown an inverse association
      between adiponectin levels and risk for multiple tumors, which is independent of
      the IGF system or other risk factors. Previous studies have shown that
      adiponectin can activate AMP-activated protein kinase (AMPK) in myocytes,
      hepatocytes, and adipocytes, suggesting that adiponectin may suppress tumor
      development through AMPK activation and subsequent inhibition of mammalian target
      of rapamycin (mTOR). However, the mechanisms through which adiponectin affects
      cancer cells are not understood, and it remains to be determined whether
      adiponectin is linked to the same downstream targets in all cells types, and in
      particular in cancer cells. In the present study, we demonstrate that while
      adiponectin stimulates AMPK in phosphatase and tensin homolog deleted on
      chromosome ten (PTEN) deficient LNCaP prostate cancer cells, it also increases
      mTOR activity as assessed by phosphorylation of two downstream targets, p70 S6
      kinase and ribosomal protein S6. This adiponectin stimulation of mTOR was
      mediated through phosphatidylinositol 3-kinase (PI3 kinase) and Akt activation.
      These results show that adiponectin can activate both AMPK and PI3 kinase/Akt
      pathways, and that cell type-specific factors such as PTEN status may determine
      which of these pathways will have the dominant effect on mTOR. Therefore, while
      it is possible that high endogenous adiponectin levels could be protective
      against cancer by direct mechanisms or indirect systemic mechanisms, our results
      indicate that adiponectin may also directly stimulate signaling pathways that
      enhance the growth of some tumors.

PMID- 18045952
TI  - Suppressor of cytokine signalling-3 is up-regulated by androgen in prostate
      cancer cell lines and inhibits androgen-mediated proliferation and secretion.
AB  - Suppressors of cytokine signalling (SOCS) are induced by interleukins (ILs) and
      various peptide hormones and may prevent sustained activation of signalling
      pathways. We have previously shown that SOCS-3 antagonizes regulation of cellular
      events by cAMP and is expressed in human prostate cancer. To investigate possible
      effects of androgen on SOCS-3 protein expression, two prostate cancer cell lines
      (PC3-AR and LAPC4) were treated with different concentrations of R1881. Western
      blot analyses revealed induction of SOCS-3 protein expression in both cell lines
      by androgen, an effect which can be blocked by the anti-androgen bicalutamide. To
      further characterize the effects of R1881 on the SOCS-3 gene, promoter-reporter
      assay and real-time PCR were performed. We found no influence of androgen on
      promoter activity or SOCS-3 mRNA levels, thus suggesting a post-transcriptional
      effect of androgen. Concordant with our previous findings, we show a significant
      increase of SOCS-3 protein after androgen treatment in cells in which
      transcription was blocked, but not in those with impaired translation. In order
      to understand implications of SOCS-3 regulation by androgen, we used SOCS-3
      negative LNCaP-IL-6 cells and stably transfected them with a tetracycline
      responsive SOCS-3 Tet-On plasmid. We report that androgenic effects on cell
      proliferation and prostate-specific antigen secretion are significantly
      diminished following up-regulation of SOCS-3. In conclusion, androgen up
      regulates SOCS-3 protein via post-transcriptional effects. SOCS-3 inhibits
      androgen-stimulated proliferation by influencing cell cycle regulation. Taken
      together with previous findings showing androgen receptor activation by IL-6, our
      results imply that androgen and cytokine signalling pathways interact at multiple
      levels in prostate cancer.

PMID- 18045953
TI  - Anti-estrogenic actions of histone deacetylase inhibitors in MCF-7 breast cancer
      cells.
AB  - Anti-estrogens are the current endocrine therapy of choice in the treatment of
      estrogen receptor (ER)-positive breast cancers. Histone deacetylase inhibitors
      (HDACi) also constitute a promising treatment for therapy, and combination of
      anti-estrogens with HDACi may improve efficacy while reducing side effects. We
      have examined the effect of the HDACi sodium butyrate and suberoylanilide
      hydroxamic acid (SAHA), alone and in combination with 17beta-estradiol (E2) and
      the pure anti-estrogen ICI 182.780 (ICI) in human MCF-7 breast cancer cells.
      HDACi caused a sustained increase of histone H3 acetylation and caused cell death
      as shown by flow cytometry analysis. In surviving cells, both inhibitors were
      even stronger than ICI in depleting cyclin D1 levels, inducing expression of the
      cyclin kinase inhibitor p21Waf1/Cip1, blocking phosphorylation of the
      retinoblastoma protein, or inhibiting cell growth. No additive effects of ICI
      with either butyrate or SAHA were found. In addition, these drugs were able to
      antagonize the effects of E2 on expression of cell cycle proteins, cell growth,
      and transcription of ER-dependent genes. The anti-estrogenic effects of HDACi
      appear to be related to a strong downregulation of the expression of ERalpha that
      appears to be secondary to both transcriptional and post-transcriptional
      regulation. ERalpha phosphorylation is involved in estrogen signaling, and HDACi
      also prevented receptor phosphorylation in Ser-118 both in the absence and
      presence of ER ligands. These results provide further support for the use of
      deacetylase inhibitors as chemotherapeutic agents in the treatment of breast
      cancer tumors.

PMID- 18045954
TI  - Cyclooxygenase-2 inhibitors prevent the development of chemoresistance phenotype
      in a breast cancer cell line by inhibiting glycoprotein p-170 expression.
AB  - Breast cancer cells are usually sensitive to several chemotherapeutic regimens,
      but they can develop chemoresistance after prolonged exposure to cytotoxic drugs,
      acquiring a more aggressive phenotype. Drug resistance might involve the multi
      drug resistance (MDR) 1 gene, encoding a transmembrane glycoprotein p-170 (P-gp),
      which antagonizes intracellular accumulation of cytotoxic agents, such as
      doxorubicin. We previously demonstrated that type 2 cyclooxygenase (COX-2)
      inhibitors can reverse the chemoresistance phenotype of a medullary thyroid
      carcinoma cell line by inhibiting P-gp expression and function. The aim of our
      study was to investigate the role of COX-2 inhibitors in modulating
      chemoresistance in a human breast cancer cell line, MCF7. MCF7 cells, expressing
      COX-2 but not MDR1, were treated with increasing doses of doxorubicin, and they
      became chemoresistant after 10 days of treatment, in association with MDR1
      expression induction. This effect was reversed by doxorubicin withdrawal and
      prevented by co-incubation with N-[2-(cyclohexyloxy)4-nitrophenyl]
      methanesulfonamide (NS-398), a selective COX-2 inhibitor. Treatment with NS-398
      alone did not influence cell viability of a resistant MCF7 cell clone (rMCF7),
      but sensitized rMCF7 cells to the cytotoxic effects of doxorubicin. Moreover,
      treatment with NS-398 significantly reduced MDR1 expression in rMCF7 cells.
      Doxorubicin-induced membrane P-gp expression and function was also greatly
      impaired. Our data therefore support the hypothesis that COX-2 inhibitors can
      prevent or reduce the development of the chemoresistance phenotype in breast
      cancer cells by inhibiting P-gp expression and function.

PMID- 18045955
TI  - CXC chemokines located in the 4q21 region are up-regulated in breast cancer.
AB  - Recent data suggest that chemokines could be essential players in breast
      carcinogenesis. We previously showed that the CXC chemokine CXCL8 (interleukin-8)
      was overexpressed in estrogen receptor alpha (ERalpha)-negative breast cell
      lines. Analysis of CXCL8 chromosomal location showed that several CXC chemokines
      (CXCL1, CXCL2, CXCL3, CXCL4, CXCL4V1, CXCL5, CXCL6, CXCL7, and CXCL8) were
      localized in the same narrow region (360 kb in size) of chromosome 4. We thus
      hypothesized that they could belong to the same cluster. Quantification of these
      chemokines in breast tumors showed that samples expressing high CXCL8 also
      produced elevated levels of CXCL1, CXCL3, and CXCL5, and displayed low content of
      ERalpha. CXCL1, CXCL2, CXCL3, CXCL5, and CXCL8 were co-regulated both in tumors
      and in breast cancer cell lines. CXCL5 and CXCL8 were mainly produced by
      epithelial cells, whereas CXCL1, CXCL2, and CXCL3 had a high expression in blood
      cells. The overexpression of these chemokines in tumor cells was not the result
      of gene amplification, but rather of an enhanced gene transcription. Our data
      suggest that high CXCL8 expression in tumors is mainly correlated to activating
      protein-1 (AP-1) pathway and to a minor extent to NF-kappaB pathway.
      Interestingly, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, and CXCL8 chemokines were
      present at higher levels in metastases when compared with grade I and III
      biopsies. High levels of CXCL8, CXCL1, and CXCL3 accounted for a shorter relapse
      free survival of ERalpha-positive patients treated with tamoxifen. In summary, we
      present evidences that multiple CXC chemokines are co-expressed in CXCL8-positive
      breast tumors. In addition, these chemokines could account for the higher
      aggressiveness of these types of tumors.

PMID- 18045956
TI  - Intratumoral IGF-I protein expression is selectively upregulated in breast cancer
      patients with BRCA1/2 mutations.
AB  - BRCA1/2 mutations predispose to early onset breast and ovarian cancers. The
      phenotypic expression of mutant alleles, however, is thought to be modified by
      factors that are also involved in the pathogenesis of sporadic breast cancer. One
      such protein is IGF-I, one of the strongest mitogens to breast cancer cells in
      vitro. We have utilized immunohistochemistry to compare the intratumoral IGF-I
      and IGF-I receptor (IGF-IR) protein expression in 57 BRCA1/2 mutation carriers
      and 102 matched breast cancer patients without a family history in a nested case
      control study. BRCA1 silencing by siRNA was used to investigate the effect of
      BRCA mutations on IGF-I protein expression. IGF-I protein expression was detected
      in tumoral epithelium and surrounding stroma, and was significantly upregulated
      in tumors of BRCA mutation carriers when compared with matched sporadic tumors
      (epithelial: 87.7% vs 61.8%, P=0.001; stromal: 73.7% vs 34.3%, P<0.001). By
      contrast, IGF-IR protein expression was confined to malignant epithelium and was
      unchanged in mutation carriers (52.6% vs 39.2%, P=0.310). While in mutation
      carriers IGF-IR protein expression was significantly correlated with both
      epithelial (P=0.003) and stromal IGF-I (P=0.02), this association was less
      pronounced in sporadic breast cancer (P=0.02 respectively). siRNA-mediated
      downregulation of BRCA1 in primary human mammary gland cells triggered
      upregulation of endogenous intracellular IGF-I in vitro. The increased
      intratumoral IGF-I protein expression in BRCA mutation carriers suggests an
      involvement of the IGF-I/IGF-IR axis in the biological behavior of breast cancers
      in this population and could define a potential therapeutic target.

PMID- 18045957
TI  - Inhibitory effects of resistin-13-peptide on the proliferation, adhesion, and
      invasion of MDA-MB-231 in human breast carcinoma cells.
AB  - To investigate the potential effects of resistin-13-peptide on the growth,
      adhesion, and invasion in human breast carcinoma cells, MDA-MB-231. 3-(4,5
      dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and colony
      forming assay were used to assess the proliferation effects of resistin-13
      peptide. The adhesive ability was investigated by cell adhesion assay, and the
      invasive potential was assessed using a transwell model. Activities of matrix
      metalloproteinase (MMP)-2 and MMP-9 were measured by zymography analysis and
      western blotting. Tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2
      were determined by western blotting. In this study, we performed in vivo
      experiments and determined the effect of resistin-13-peptide on tumor growth and
      other organs, especially ovaries in a xenograft model using the cell line
      studied. Resistin-13-peptide inhibited MDA-MB-231 cell growth and colony
      formation in a dose- and time-dependent manner. Meanwhile, the invasive and
      adhesive abilities of MDA-MB-231 cells were yet cut down by resistin-13-peptide
      in a dose-dependent manner. Resistin-13-peptide decreased the gelatinolytic
      activities of both MMP-2 and MMP-9 and enhanced the protein expression of TIMP-1
      and TIMP-2, which were secreted from the MDA-MB-231 cells. The animal experiments
      found that the growth of tumors was repressed by resistin-13-peptide, which
      affected other organs in the same time. Especially, ovaries did not have
      pathological changes yet. Treatment with resistin-13-peptide is effective in
      suppressing tumor proliferation, adhesion, and invasion. The possible mechanism
      is downregulation of MMPs and upregulation of TIMPs.

PMID- 18045958
TI  - MEN1 mutation analysis in Chinese patients with multiple endocrine neoplasia type
      1.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumour syndrome
      characterized by the development of tumours of the parathyroid, anterior
      pituitary and pancreatic islets, etc. Heterozygous germ line mutations of MEN1
      gene are responsible for the onset of MEN1. We investigated the probands and 31
      family members from eight unrelated Chinese families associated with MEN1 and
      identified four novel mutations, namely 373_374ins18, 822delT, 259delT and
      1092delC, as well as three previously reported mutations, such as 357_360delCTGT,
      427_428delTA and R108X (CGA>TGA) of MEN1 gene. Furthermore, we detected a loss of
      heterozygosity (LOH) at chromosome 11q in the removed tumours, including
      gastrinoma, insulinoma and parathyroid adenoma from two probands of MEN1
      families. RT-PCR and direct sequencing showed that mutant MEN1 transcripts
      remained in the MEN1-associated endocrine tumours, whereas normal menin proteins
      could not be detected in those tumours by either immunohistochemistry or
      immunoblotting. In conclusion, MEN1 heterozygous mutations are associated with
      LOH and menin absence, which are present in MEN1-associated endocrine tumours.

PMID- 18045959
TI  - Expression and functional consequences of oestrogen and progesterone receptors in
      human insulinomas.
AB  - The expression of steroid receptors by tumours offers a therapeutic advantage if
      functionally responsive to exogenous hormones. Insulinomas represent a highly
      symptomatic group of pancreatic tumours and the steroid receptor status of these
      tumours is poorly understood. The object of the study was to characterise the sex
      steroid receptor status of human insulinomas and to investigate whether sex
      steroids alter insulin expression therein. At our tertiary referral University
      Hospital, archival and prospective tissues from 25 insulinoma patients collected
      over 14 years were analysed for oestrogen receptor-alpha (ERalpha), oestrogen
      receptor beta (ERbeta) and progesterone receptor (PR) expression. Tissue explants
      of insulinoma and control pancreatic tissue from two new insulinoma patients were
      cultured and treated with oestrogen and progesterone and insulin expression
      measured by RT-PCR and ELISA. The main outcome measures were established before
      data collection and included sex steroid receptor status of tumours and insulin
      expression in fresh tissue in response to exogenous sex steroids. PR was
      expressed in 24 out of 25, ERalpha in 10 out of 25 and ERbeta in 21 out of 25
      insulinomas. In fresh insulinoma cultures, insulin expression was increased by
      oestrogen or progesterone, whereas no significant effect was observed in adjacent
      pancreatic tissue. This study demonstrates widespread expression of sex steroid
      receptors on human insulinoma tissue and provides in vitro evidence of
      functionality with increased expression of insulin by insulinoma explants in
      response to exogenous oestrogen or progesterone. Confirmation of these results
      may provide a therapeutic mechanism for reducing symptomatic insulin secretion by
      receptor blockade.

PMID- 18045960
TI  - Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine
      needle aspiration biopsy with cytological findings suspicious for papillary
      thyroid carcinoma.
AB  - Ten to fifteen percent of fine-needle aspiration biopsy (FNAB) of thyroid nodules
      are indeterminate. Galectin-3 (Gal-3) and the oncogene BRAFV600E are markers of
      malignancy useful to improve FNAB accuracy. The objective of this study was to
      determine whether the combined analysis of Gal-3 and BRAFV600E expression in
      thyroid aspirates could improve the diagnosis in FNAB with suspicious cytological
      findings. Two hundred and sixty-one surgical thyroid tissues and one hundred and
      forty-four thyroid aspirates were analyzed for the presence of the two markers.
      In surgical specimens, Gal-3 expression was present in 27.4% benign nodules,
      91.9% papillary (PTC) and 75% follicular (FTC) thyroid carcinomas. BRAFV600E was
      not detected in 127 benign nodules, as well as in 32 FTCs, while was found in
      42.9% PTC. No correlation was found between BRAF mutation and Gal-3 expression.
      Forty-seven consecutive FNAB suspicious for PTC were analyzed for the presence of
      the two markers. Of these nodules, 23 were benign at histology, 6 were positive
      for Gal-3, none displayed BRAFV600E, and 17 were negative for both the markers.
      Twenty suspicious nodules were diagnosed as PTC and four FTCs at histology. Of
      these 24 carcinomas, 9 resulted positive for BRAFV600E, 17 for Gal-3, and 22 for
      one or both the markers. The sensitivity, specificity, and accuracy for the
      presence of Gal-3 and/or BRAFV600E were significantly higher than those obtained
      for the two markers alone. Notably, the negative predictive value increased from
      70.8 to 89.5%. In conclusion, the combined detection of Gal-3 and BRAFV600E
      improves the diagnosis in FNAB with cytological findings suspicious for PTC and
      finds clinical application in selected cases.

PMID- 18045961
TI  - Clinically unpredictable prognostic factors in the outcome of medullary thyroid
      cancer.
AB  - Total thyroidectomy and central neck dissection are the procedures of choice in
      patients affected with medullary thyroid cancer. It is known that a medullary
      thyroid cancer with node metastases can be rarely cured, and therefore the
      utility of a modified radical neck dissection in the absence of suspicious node
      metastases still needs further evidence. The study aims to verify whether other
      epidemiological and pathological parameters could affect the prognosis of
      medullary thyroid cancer patients. We prospectively studied 70 medullary thyroid
      cancer patients consecutively operated on (from 2000 to 2004) at the same
      institution and analysed by the same pathologists. All patients underwent total
      thyroidectomy and central lymphadenectomy. In 27 cases, the ipsilateral (n=19) or
      bilateral (n=8) modified radical neck dissection was performed in the presence of
      suspicious lateral neck node metastases. After surgical treatment, basal and
      stimulated serum calcitonins (Cts) were measured in all patients. Follow-up
      ranged between 1 and 4 years. Patients were considered 'cured' when stimulated Ct
      was undetectable. Age, sex, tumour size, tumour capsule, multicentricity, nodes
      in the central neck and mean number of positive nodes were analysed in 'cured'
      and 'not-cured' patients. The presence of node metastases in the central
      compartment was significantly correlated with the outcome of the patients, being
      present in 9 and 72% of cured and not-cured patients respectively (P<0.000001).
      Tumour size was also significantly correlated with the outcome of the disease
      (P<0.00006). The presence of the tumour capsule correlated with better prognosis
      (P=0.0005) and absence of node metastases (P=0.0080). By multivariate analysis,
      the presence of node metastasis remained the most significant variable affecting
      the outcome of the disease (P=0.000014). Our results show that the outcome of
      encapsulated cancer is significantly better regardless of tumour size and node
      metastases. Although the early diagnosis and the extensive surgical treatment may
      favour the good outcome of medullary thyroid cancer, they do not always guarantee
      the definitive cure of the disease, being the capsular infiltration an
      independent bad prognostic factor.

PMID- 18045962
TI  - Growth inhibition of human salivary gland tumor cells by introduction of
      progesterone (Pg) receptor and Pg treatment.
AB  - Cancer of the salivary gland is one of the common cancers in the head and the
      neck regions. This type of cancer develops in the minor and the major salivary
      glands, and it sometimes metastasizes to other organs, particularly the lung.
      Morphologic mimicry and similarity in the expression of steroid hormone receptors
      between salivary gland tumors (SGTs) and breast tumors are well-known phenomena
      and are occasionally debated in the field of surgical pathology. Progesterone
      (Pg), one of the female sex steroid hormone, is intimately involved in the
      development of the mammary gland. Further, it is believed that Pg plays a role in
      breast cancer progression. However, little is known regarding its role in SGTs.
      In this study, we used ACCM, a human adenoid cystic carcinoma cell line
      established from the salivary gland, in order to clarify the role of the Pg
      receptor (PR) on cell proliferation. No effect of Pg on cell proliferation was
      observed in the PR-deficient aggressive ACCM cells. However, after introducing PR
      into the ACCM cells, Pg markedly inhibited the proliferative activity of the
      cells. This inhibitory effect on cell proliferation was accompanied by p21
      upregulation, and Id1 and c-myc downregulation. Moreover, Pg-treated PR
      transfectants showed significant morphological change; they appeared more
      flattened and spread out when compared with the ethanol-treated control cells.
      Our results provided significant insights into the mechanism of suppression of
      the proliferative property of the cells via the function of PR, and suggested
      that PR reintroduction therapy might be a viable method of inhibiting human SGT
      progression.

PMID- 18045963
TI  - Vasopressin triggers senescence in K-ras transformed cells via RhoA-dependent
      downregulation of cyclin D1.
AB  - Arginine vasopressin (AVP), a vasoactive peptide hormone that binds to three G
      protein coupled receptors (V1R, V2R, and V3R), has long been known to activate
      V1R and elicit mitogenesis in several cell types, including adrenal glomerulosa
      cells. However, in the mouse Y1 adrenocortical malignant cell line, AVP triggers
      not only a canonical mitogenic response but also novel RhoA-GTP-dependent
      mechanisms which downregulate cyclin D1, irreversibly inhibiting K-ras oncogene
      driven proliferation. In Y1 cells, AVP blocks cyclin D1 expression, induces
      senescence-associated beta-galactosidase (SAbeta-Gal) and inhibits proliferation.
      However, ectopic expression of cyclin D1 renders Y1 cells resistant to both
      SAbeta-Gal induction and proliferation inhibition by AVP. In addition, ectopic
      expression of the dominant negative RhoAN19 mutant blocks RhoA activation,
      yielding Y1 cell sub-lines which are no longer susceptible to cyclin D1
      downregulation, SAbeta-Gal induction, or proliferation inhibition by AVP.
      Furthermore, inhibiting RhoA with C3 exoenzyme protects Y1 cells from AVP
      proliferation inhibition and SAbeta-Gal induction. On the other hand, AVP
      treatment does not activate caspases 3 and 7, and the caspase inhibitor Ac-DEVD
      CMK does not protect Y1 cells from proliferation inhibition by AVP, implying that
      AVP does not trigger apoptosis. These results underline a pivotal survival
      activity of cyclin D1 that protects K-ras oncogene-dependent malignant cells from
      senescence.

PMID- 18045964
TI  - Multifractality in the peripheral cardiovascular system from pointwise holder
      exponents of laser Doppler flowmetry signals.
AB  - We study the dynamics of skin laser Doppler flowmetry signals giving a peripheral
      view of the cardiovascular system. The analysis of Holder exponents reveals that
      the experimental signals are weakly multifractal for young healthy subjects at
      rest. We implement the same analysis on data generated by a standard theoretical
      model of the cardiovascular system based on nonlinear coupled oscillators with
      linear couplings and fluctuations. We show that the theoretical model, although
      it captures basic features of the dynamics, is not complex enough to reflect the
      multifractal irregularities of microvascular mechanisms.

PMID- 18045965
TI  - Fibroblast adaptation and stiffness matching to soft elastic substrates.
AB  - Many cell types alter their morphology and gene expression profile when grown on
      chemically equivalent surfaces with different rigidities. One expectation of this
      change in morphology and composition is that the cell's internal stiffness,
      governed by cytoskeletal assembly and production of internal stresses, will
      change as a function of substrate stiffness. Atomic force microscopy was used to
      measure the stiffness of fibroblasts grown on fibronectin-coated polyacrylamide
      gels of shear moduli varying between 500 and 40,000 Pa. Indentation measurements
      show that the cells' elastic moduli were equal to, or slightly lower than, those
      of their substrates for a range of soft gels and reached a saturating value at a
      substrate rigidity of 20 kPa. The amount of cross-linked F-actin sedimenting at
      low centrifugal force also increased with substrate stiffness. Together with
      enhanced actin polymerization and cross-linking, active contraction of the
      cytoskeleton can also modulate stiffness by exploiting the nonlinear elasticity
      of semiflexible biopolymer networks. These results suggest that within a range of
      stiffness spanning that of soft tissues, fibroblasts tune their internal
      stiffness to match that of their substrate, and modulation of cellular stiffness
      by the rigidity of the environment may be a mechanism used to direct cell
      migration and wound repair.

PMID- 18045966
TI  - Nineteenth Annual Pezcoller Symposium: hypothesis-driven clinical investigation
      in cancer.
AB  - This symposium was held in Trento, Italy, from June 14 to 16, 2007, and was co
      chaired by William G. Kaelin, Enrico Mihich, and Charles L. Sawyers. A session
      was devoted to the proof of concept derived from successes in target-oriented
      therapeutics. Molecular targets must be identified in each patients because they
      are equally present in all patients with the same tumor type. A session was
      devoted to the identification of markers of drug effectiveness. Two sessions were
      focused on opportunities for developing new specific molecular target-oriented
      therapies.

PMID- 18045967
TI  - Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft
      versus-host disease.
AB  - Much of the efficacy of allogeneic hematopoietic stem cell transplantation
      (alloSCT) in curing hematologic malignancies is due to a graft-versus-leukemia
      (GVL) effect mediated by donor T cells that recognize recipient alloantigens on
      leukemic cells. Donor T cells are also important for reconstituting immunity in
      the recipient. Unfortunately, donor T cells can attack nonmalignant host tissues
      and cause graft-versus-host disease (GVHD). We previously reported that donor
      CD4(+) effector memory T cells (T(EMs)) do not cause GVHD but transfer functional
      T-cell memory. In the present work, we demonstrate in an MHC-mismatched model
      that CD4(+) T(EMs) (unprimed to recipient antigens) mediate GVL against
      clinically relevant mouse models of chronic phase and blast crisis chronic
      myelogenous leukemia, without causing GVHD. By creating gene-deficient leukemias
      and using perforin-deficient T cells, we demonstrate that direct cytolytic
      function is essential for T(EM)-mediated GVL, but that GVL is retained when
      killing via FasL, TNF-alpha, TRAIL, and perforin is individually impaired.
      However, T(EM)-mediated GVL was diminished when both FasL and perforin pathways
      were blocked. Taken together, our studies identify T(EMs) as a clinically
      applicable cell therapy for promoting GVL and immune reconstitution, particularly
      in MHC-mismatched haploidentical alloSCTs in which T cell-depleted allografts are
      commonly used to minimize GVHD.

PMID- 18045969
TI  - Short telomeres are associated with genetic complexity, high-risk genomic
      aberrations, and short survival in chronic lymphocytic leukemia.
AB  - Telomere length is associated with mutation status of the immunoglobulin heavy
      chain variable (IGHV) gene and clinical course in B-cell chronic lymphocytic
      leukemia (B-CLL). In a B-CLL cohort of 152 patients, we analyzed telomere length,
      genomic aberrations, IGHV mutation status, CD38 and ZAP-70 expression to study
      the prognostic impact and associations among these factors. An inverse
      correlation existed between telomere length and IGHV homology (P < .001), CD38 (P
      < .001), and ZAP-70 expression (P = .01). Patients with telomere lengths below
      median (ie, "short telomeres") and above median (ie, "long telomeres") had
      similar incidences of genomic aberrations (74% vs 68%), 13q- (57% vs 49%), and
      +12q (5% vs 12%). In contrast, 13q- as a single aberration was more frequent in
      patients with long telomeres (51% vs 21%; P = .006), whereas 11q- (27% vs 9%; P =
      .014), 17p- (17% vs 0%; P < .001), and 2 or more genomic aberrations (39% vs 8%;
      P < .001) were more frequent in patients with short telomeres. Compared with
      patients with long telomeres, treatment-free survival (TFS) and overall survival
      (OS) was significantly shorter (P < .001 and P = .015, respectively) in the group
      with short telomeres, and telomere length was an independent prognostic indicator
      for TFS. These observations have biological and prognostic implications in B-CLL.

PMID- 18045968
TI  - Prophylactic thrombolysis by thrombin-activated latent prourokinase targeted to
      PECAM-1 in the pulmonary vasculature.
AB  - A recombinant prodrug, single-chain urokinase-type plasminogen activator (scuPA)
      fused to an anti-PECAM-1 antibody single-chain variable fragment (anti-PECAM
      scFv/scuPA) targets endothelium and augments thrombolysis in the pulmonary
      vasculature.(1) To avoid premature activation and inactivation and to limit
      systemic toxicity, we replaced the native plasmin activation site in scFv/low
      molecular-weight (lmw)-scuPA with a thrombin activation site, generating anti
      PECAM scFv/uPA-T that (1) is latent and activated by thrombin instead of plasmin;
      (2) binds to PECAM-1; (3) does not consume plasma fibrinogen; (4) accumulates in
      mouse lungs after intravenous injection; and (5) resists PA inhibitor PAI-1 until
      activated by thrombin. In mouse models of pulmonary thrombosis caused by
      thromboplastin and ischemia-reperfusion (I/R), scFv/uPA-T provided more potent
      thromboprophylaxis and greater lung protection than plasmin-sensitive scFv/uPA.
      Endothelium-targeted thromboprophylaxis triggered by a prothrombotic enzyme
      illustrates a novel approach to time- and site-specific regulation of proteolytic
      reactions that can be modulated for therapeutic benefit.

PMID- 18045970
TI  - Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human
      dendritic cells.
AB  - Clinical trials have been started with the aim of inducing tumor immunity by
      blocking the immunosuppressive action of indoleamine-2,3-dioxygenase (IDO) with
      the IDO2-inhibitor dextro-1-methyl-tryptophan (D-1MT). Here we show that human
      dendritic cells (DCs) express both IDO-1 and IDO-2, but that only IDO1 mediates
      tryptophan catabolism; furthermore, its activity is blocked by levo-1MT, whereas
      D-1MT is inefficient. Consequently, in humans any possible antitumor effects of D
      1MT cannot be attributed to abrogation of IDO activity in DCs as described in
      this study.

PMID- 18045972
TI  - Guidelines on prevention of transmission of hepatitis C virus infection in the
      workplace: do they work in practice?

PMID- 18045971
TI  - Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac
      of human embryos.
AB  - Mesenchymal stem cells (MSCs) are multipotent stem cells that can generate
      various microenvironment components in bone marrow, ensuring a precise control
      over self-renewal and multilineage differentiation of hematopoietic stem cells.
      Nevertheless, their spatiotemporal correlation with embryonic hematopoiesis
      remains rudimentary, particularly in relation to the human being. Here, we
      reported that human aorta-gonad-mesonephros (AGM) resided with bona fide MSCs.
      They were highly proliferative as fibroblastoid population bearing uniform
      surface markers (CD45(-), CD34(-), CD105(+), CD73(+), CD29(+), and CD44(+)),
      expressed pluripotential molecules Oct-4 and Nanog, and clonally demonstrated
      trilineage differentiation capacity (osteocytes, chondrocytes, and adipocytes).
      The frequency and absolute number of MSCs in aorta plus surrounding mesenchyme
      (E26-E27) were 0.3% and 164, respectively. Moreover, they were functionally
      equivalent to MSCs from adult bone marrow, that is, supporting long-term
      hematopoiesis and suppressing T-lymphocyte proliferation in vitro. In comparison,
      the matching yolk sac contained bipotent mesenchymal precursors that propagated
      more slowly and failed to generate chondrocytes in vitro. Together with previous
      knowledge, we propose that a proportion of MSCs initially develop in human AGM
      prior to their emergence in embryonic circulation and fetal liver.

PMID- 18045973
TI  - Blood-borne virus screening in health care workers: is it worthwhile?

PMID- 18045974
TI  - Immunization and health workers: overview.

PMID- 18045975
TI  - The immunological principles underlying vaccine-induced protection in the
      occupational health setting.
AB  - Abstract Protection against the large numbers of pathogenic microbes to which
      humans are constantly exposed is effected through external barriers (skin and
      mucus membranes), innate barriers (cellular components and soluble chemical
      mediators) and adaptive barriers (B and T lymphocytes). This article reviews the
      normal mechanisms employed to protect against these pathogenic microbes.

PMID- 18045976
TI  - Active and passive immunity, vaccine types, excipients and licensing.
AB  - Abstract Immunity is the state of protection against infectious disease conferred
      either through an immune response generated by immunization or previous infection
      or by other non-immunological factors. This article reviews active and passive
      immunity and the differences between them: it also describes the four different
      commercially available vaccine types (live attenuated, killed/inactivated,
      subunit and toxoid): it also looks at how these different vaccines generate an
      adaptive immune response.

PMID- 18045977
TI  - Specific immunization issues in the occupational health setting.
AB  - This article looks at the components of an effective occupational health
      vaccination programme and also reviews the legal basis for them. It addresses the
      issue of vaccine licensing including pre-clinical, clinical and post-licensing
      studies. It explores screening for vaccine preventable diseases in the
      occupational health setting and then addresses particular issues around hepatitis
      B, chicken pox, tuberculosis, measles, rubella, diphtheria, polio, mumps and
      hepatitis A.

PMID- 18045978
TI  - CPD for GPs using the THOR-GP website.
AB  - BACKGROUND: An estimated 3200 UK general practitioners (GPs) practise
      occupational medicine on a sessional basis. AIM: To assess the educational needs
      of GPs practising occupational medicine and participating in The Health and
      Occupational Reporting (THOR) network. METHODS: A questionnaire survey of GPs
      participating in a national reporting scheme, recording occupational ill-health
      from general practice (THOR-GP). The questionnaire used scales derived from the
      syllabus for the Diploma of the Faculty of Occupational Medicine to assess the
      use of the THOR-GP website for continuing professional development (CPD).
      Questions were also asked concerning the attitudes and experience of these
      doctors to CPD in occupational medicine. RESULTS: The response rate was 73%
      (213/291). Only 22% of responders used the THOR-GP website for CPD. Lack of time
      was the most frequently cited reason for not using the site. The topics provided
      on the website which were rated least interesting also appeared as requests for
      further information in questionnaire returns. CONCLUSION: Online learning has the
      potential to fulfil the needs of GPs practising occupational medicine. The
      designers of material for online learning should actively manage and modify the
      material available in response to educational needs. Further research is required
      into the clinical and business outcomes of online learning for these doctors.

PMID- 18045979
TI  - Occupational health physicians and tribunals.

PMID- 18045980
TI  - Health-related quality of life in former North Sea divers.

PMID- 18045981
TI  - Modernizing medical careers.

PMID- 18045982
TI  - Towards uniform requirements for manuscripts submitted to journals in
      occupational medicine.

PMID- 18045984
TI  - Stochastic frontier analysis of hospital inefficiency: a review of empirical
      issues and an assessment of robustness.
AB  - Twenty stochastic frontier analysis (SFA) studies of hospital inefficiency in the
      United States were analyzed. Results from best-practice methods were compared
      against previously used methods in hospital studies to ascertain the robustness
      of SFA in estimating cost inefficiency. To compare past studies and analyze new
      data, SFA methods were varied by (a) the assumptions of the structure of costs
      and distribution of the error term, (b) inclusion of quality and product
      descriptor measures, and (c) use of simultaneous and two-stage estimation
      techniques. SFA results were relatively insensitive to several model variations.

PMID- 18045985
TI  - How federal and state policies affected hospital uncompensated care provision in
      the 1990s.
AB  - The 1990s featured pronounced policy change that had important effects on safety
      net providers and their ability to care for the uninsured. The authors examined
      how changes in public policy affected hospital uncompensated care (UC) between
      1990 and 2000. They found that aggregate state Medicaid Disproportionate Share
      Hospital spending had no impact on UC provision. Expanding public health
      insurance eligibility for children and adults and increasing Medicaid managed
      care had small negative effects on UC provision. State and local tax
      appropriations had the largest impact on UC provision. A better understanding of
      the effect of health care policies on UC provision is essential in crafting new
      policies and better anticipating their impact.

PMID- 18045986
TI  - KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in
      vertebrates.
AB  - Chromosome segregation during mitosis requires the assembly of a large
      proteinaceous structure termed the kinetochore. In Caenorhabditis elegans, KNL-1
      is required to target multiple outer kinetochore proteins. Here, we demonstrate
      that the vertebrate KNL1 counterpart is essential for chromosome segregation and
      is required to localize a subset of outer kinetochore proteins. However, unlike
      in C. elegans, depletion of vertebrate KNL1 does not abolish kinetochore
      localization of the microtubule-binding Ndc80 complex. Instead, we show that KNL1
      and CENP-K, a subunit of a constitutively centromere-associated complex that is
      missing from C. elegans, coordinately direct Ndc80 complex localization.
      Simultaneously reducing both hKNL1 and CENP-K function abolishes all aspects of
      kinetochore assembly downstream of centromeric chromatin and causes catastrophic
      chromosome segregation defects. These findings explain discrepancies in
      kinetochore assembly pathways between different organisms and reveal a surprising
      plasticity in the assembly mechanism of an essential cell division organelle.

PMID- 18045987
TI  - B-RAF regulation of Rnd3 participates in actin cytoskeletal and focal adhesion
      organization.
AB  - The actin cytoskeleton controls multiple cellular functions, including cell
      morphology, movement, and growth. Accumulating evidence indicates that oncogenic
      activation of the mitogen-activated protein kinase kinase/extracellular signal
      regulated kinase 1/2 (MEK/ERK1/2) pathway is accompanied by actin cytoskeletal
      reorganization. However, the signaling events contributing to actin cytoskeleton
      remodeling mediated by aberrant ERK1/2 activation are largely unknown. Mutant B
      RAF is found in a variety of cancers, including melanoma, and it enhances
      activation of the MEK/ERK1/2 pathway. We show that targeted knockdown of B-RAF
      with small interfering RNA or pharmacological inhibition of MEK increased actin
      stress fiber formation and stabilized focal adhesion dynamics in human melanoma
      cells. These effects were due to stimulation of the Rho/Rho kinase (ROCK)/LIM
      kinase-2 signaling pathway, cumulating in the inactivation of the actin
      depolymerizing/severing protein cofilin. The expression of Rnd3, a Rho
      antagonist, was attenuated after B-RAF knockdown or MEK inhibition, but it was
      enhanced in melanocytes expressing active B-RAF. Constitutive expression of Rnd3
      suppressed the actin cytoskeletal and focal adhesion effects mediated by B-RAF
      knockdown. Depletion of Rnd3 elevated cofilin phosphorylation and stress fiber
      formation and reduced cell invasion. Together, our results identify Rnd3 as a
      regulator of cross talk between the RAF/MEK/ERK and Rho/ROCK signaling pathways,
      and a key contributor to oncogene-mediated reorganization of the actin
      cytoskeleton and focal adhesions.

PMID- 18045988
TI  - Myosin transducer mutations differentially affect motor function, myofibril
      structure, and the performance of skeletal and cardiac muscles.
AB  - Striated muscle myosin is a multidomain ATP-dependent molecular motor.
      Alterations to various domains affect the chemomechanical properties of the
      motor, and they are associated with skeletal and cardiac myopathies. The myosin
      transducer domain is located near the nucleotide-binding site. Here, we helped
      define the role of the transducer by using an integrative approach to study how
      Drosophila melanogaster transducer mutations D45 and Mhc(5) affect myosin
      function and skeletal and cardiac muscle structure and performance. We found D45
      (A261T) myosin has depressed ATPase activity and in vitro actin motility, whereas
      Mhc(5) (G200D) myosin has these properties enhanced. Depressed D45 myosin
      activity protects against age-associated dysfunction in metabolically demanding
      skeletal muscles. In contrast, enhanced Mhc(5) myosin function allows normal
      skeletal myofibril assembly, but it induces degradation of the myofibrillar
      apparatus, probably as a result of contractile disinhibition. Analysis of beating
      hearts demonstrates depressed motor function evokes a dilatory response, similar
      to that seen with vertebrate dilated cardiomyopathy myosin mutations, and it
      disrupts contractile rhythmicity. Enhanced myosin performance generates a
      phenotype apparently analogous to that of human restrictive cardiomyopathy,
      possibly indicating myosin-based origins for the disease. The D45 and Mhc(5)
      mutations illustrate the transducer's role in influencing the chemomechanical
      properties of myosin and produce unique pathologies in distinct muscles. Our data
      suggest Drosophila is a valuable system for identifying and modeling mutations
      analogous to those associated with specific human muscle disorders.

PMID- 18045989
TI  - The Golgi protein GM130 regulates centrosome morphology and function.
AB  - The Golgi apparatus (GA) of mammalian cells is positioned in the vicinity of the
      centrosome, the major microtubule organizing center of the cell. The significance
      of this physical proximity for organelle function and cell cycle progression is
      only beginning to being understood. We have identified a novel function for the
      GA protein, GM130, in the regulation of centrosome morphology, position and
      function during interphase. RNA interference-mediated depletion of GM130 from
      five human cell lines revealed abnormal interphase centrosomes that were
      mispositioned and defective with respect to microtubule organization and cell
      migration. When GM130-depleted cells entered mitosis, they formed multipolar
      spindles, arrested in metaphase, and died. We also detected aberrant centrosomes
      during interphase and multipolar spindles during mitosis in ldlG cells, which do
      not contain detectable GM130. Although GA proteins have been described to
      regulate mitotic centrosomes and spindle formation, this is the first report of a
      role for a GA protein in the regulation of centrosomes during interphase.

PMID- 18045990
TI  - The 90-kDa heat shock protein stabilizes the polysomal ribonuclease 1 mRNA
      endonuclease to degradation by the 26S proteasome.
AB  - The polysomal ribonuclease 1 (PMR1) mRNA endonuclease forms a selective complex
      with its translating substrate mRNAs where it is activated to initiate mRNA
      decay. Previous work showed tyrosine phosphorylation is required for PMR1
      targeting to this polysome-bound complex, and it identified c-Src as the
      responsible kinase. c-Src phosphorylation occurs in a distinct complex, and the
      current study shows that 90-kDa heat shock protein (Hsp90) is also recovered with
      PMR1 and c-Src. Hsp90 binding to PMR1 is inhibited by geldanamycin, and
      geldanamycin stabilizes substrate mRNA to PMR1-mediated decay. PMR1 is inherently
      unstable and geldanamycin causes PMR1 to rapidly disappear in a process that is
      catalyzed by the 26S proteasome. We present a model where Hsp90 interacts
      transiently to stabilize PMR1 in a manner similar to its interaction with c-Src,
      thus facilitating the tyrosine phosphorylation and targeting of PMR1 to
      polysomes.

PMID- 18045991
TI  - Transmembrane domain interactions control biological functions of neuropilin-1.
AB  - Neuropilin-1 (NRP1) is a transmembrane receptor playing a pivotal role in the
      control of semaphorins and VEGF signaling pathways. The exact mechanism
      controlling semaphorin receptor complex formation is unknown. A structural
      analysis and modeling of NRP1 revealed a putative dimerization GxxxG motif
      potentially important for NRP1 dimerization and oligomerization. Our data show
      that this motif mediates the dimerization of the transmembrane domain of NRP1 as
      demonstrated by a dimerization assay (ToxLuc assay) performed in natural membrane
      and FRET analysis. A synthetic peptide derived from the transmembrane segment of
      NRP1 abolished the inhibitory effect of Sema3A. This effect depends on the
      capacity of the peptide to interfere with NRP1 dimerization and the formation of
      oligomeric complexes. Mutation of the GxxxG dimerization motif in the
      transmembrane domain of NRP1 confirmed its biological importance for Sema3A
      signaling. Overall, our results shed light on an essential step required for
      semaphorin signaling and provide novel evidence for the crucial role of
      transmembrane domain of bitopic protein containing GxxxG motif in the formation
      of receptor complexes that are a prerequisite for cell signaling.

PMID- 18045992
TI  - PP2A regulates HDAC4 nuclear import.
AB  - Different signal-regulated serine/threonine kinases phosphorylate class II
      histone deacetylases (HDACs) to promote nuclear export, cytosolic accumulation,
      and activation of gene transcription. However, little is known about mechanisms
      operating in the opposite direction, which, possibly through phosphatases, should
      promote class II HDACs nuclear entry and subsequent gene repression. Here we show
      that HDAC4 forms a complex with the PP2A holoenzyme C alpha, A alpha, B/PR55
      alpha. In vitro and in vivo binding studies demonstrate that the N-terminus of
      HDAC4 interacts with the catalytic subunit of PP2A. HDAC4 is dephosphorylated by
      PP2A and experiments using okadaic acid or RNA interference have revealed that
      PP2A controls HDAC4 nuclear import. Moreover, we identified serine 298 as a
      putative phosphorylation site important for HDAC4 nuclear import. The HDAC4
      mutant mimicking phosphorylation of serine 298 is defective in nuclear import.
      Mutation of serine 298 to alanine partially rescues the defect in HDAC4 nuclear
      import observed in cells with down-regulated PP2A. These observations suggest
      that PP2A, via the dephosphorylation of multiple serines including the 14-3-3
      binding sites and serine 298, controls HDAC4 nuclear import.

PMID- 18045993
TI  - RFCCtf18 and the Swi1-Swi3 complex function in separate and redundant pathways
      required for the stabilization of replication forks to facilitate sister
      chromatid cohesion in Schizosaccharomyces pombe.
AB  - Sister chromatid cohesion is established during S phase near the replication
      fork. However, how DNA replication is coordinated with chromosomal cohesion
      pathway is largely unknown. Here, we report studies of fission yeast Ctf18, a
      subunit of the RFC(Ctf18) replication factor C complex, and Chl1, a putative DNA
      helicase. We show that RFC(Ctf18) is essential in the absence of the Swi1-Swi3
      replication fork protection complex required for the S phase stress response.
      Loss of Ctf18 leads to an increased sensitivity to S phase stressing agents, a
      decreased level of Cds1 kinase activity, and accumulation of DNA damage during S
      phase. Ctf18 associates with chromatin during S phase, and it is required for the
      proper resumption of replication after fork arrest. We also show that chl1Delta
      is synthetically lethal with ctf18Delta and that a dosage increase of chl1(+)
      rescues sensitivities of swi1Delta to S phase stressing agents, indicating that
      Chl1 is involved in the S phase stress response. Finally, we demonstrate that
      inactivation of Ctf18, Chl1, or Swi1-Swi3 leads to defective centromere cohesion,
      suggesting the role of these proteins in chromosome segregation. We propose that
      RFC(Ctf18) and the Swi1-Swi3 complex function in separate and redundant pathways
      essential for replication fork stabilization to facilitate sister chromatid
      cohesion in fission yeast.

PMID- 18045994
TI  - Sequestration of mutated alpha1-antitrypsin into inclusion bodies is a cell
      protective mechanism to maintain endoplasmic reticulum function.
AB  - A variant alpha1-antitrypsin with E342K mutation has a high tendency to form
      intracellular polymers, and it is associated with liver disease. In the
      hepatocytes of individuals carrying the mutation, alpha1-antitrypsin localizes
      both to the endoplasmic reticulum (ER) and to membrane-surrounded inclusion
      bodies (IBs). It is unclear whether the IBs contribute to cell toxicity or
      whether they are protective to the cell. We found that in hepatoma cells, mutated
      alpha1-antitrypsin exited the ER and accumulated in IBs that were negative for
      autophagosomal and lysosomal markers, and contained several ER components, but
      not calnexin. Mutated alpha1-antitrypsin induced IBs also in neuroendocrine
      cells, showing that formation of these organelles is not cell type specific. In
      the presence of IBs, ER function was largely maintained. Increased levels of
      calnexin, but not of protein disulfide isomerase, inhibited formation of IBs and
      lead to retention of mutated alpha1-antitrypsin in the ER. In hepatoma cells,
      shift of mutated alpha1-antitrypsin localization to the ER by calnexin
      overexpression lead to cell shrinkage, ER stress, and impairment of the secretory
      pathway at the ER level. We conclude that segregation of mutated alpha1
      antitrypsin from the ER to the IBs is a protective cell response to maintain a
      functional secretory pathway.

PMID- 18045995
TI  - Conversion of a replication origin to a silencer through a pathway shared by a
      Forkhead transcription factor and an S phase cyclin.
AB  - Silencing of the mating-type locus HMR in Saccharomyces cerevisiae requires DNA
      elements called silencers. To establish HMR silencing, the origin recognition
      complex binds the HMR-E silencer and recruits the silent information regulator
      (Sir)1 protein. Sir1 in turn helps establish silencing by stabilizing binding of
      the other Sir proteins, Sir2-4. However, silencing is semistable even in
      sir1Delta cells, indicating that SIR1-independent establishment mechanisms exist.
      Furthermore, the requirement for SIR1 in silencing a sensitized version of HMR
      can be bypassed by high-copy expression of FKH1 (FKH1(hc)), a conserved forkhead
      transcription factor, or by deletion of the S phase cyclin CLB5 (clb5Delta).
      FKH1(hc) caused only a modest increase in Fkh1 levels but effectively
      reestablished Sir2-4 chromatin at HMR as determined by Sir3-directed chromatin
      immunoprecipitation. In addition, FKH1(hc) prolonged the cell cycle in a manner
      distinct from deletion of its close paralogue FKH2, and it created a cell cycle
      phenotype more reminiscent to that caused by a clb5Delta. Unexpectedly, and in
      contrast to SIR1, both FKH1(hc) and clb5Delta established silencing at HMR using
      the replication origins, ARS1 or ARSH4, as complete substitutes for HMR-E
      (HMRDeltaE::ARS). HMRDeltaE::ARS1 was a robust origin in CLB5 cells. However,
      initiation by HMRDeltaE::ARS1 was reduced by clb5Delta or FKH1(hc), whereas ARS1
      at its native locus was unaffected. The CLB5-sensitivity of HMRDeltaE::ARS1 did
      not result from formation of Sir2-4 chromatin because sir2Delta did not rescue
      origin firing in clb5Delta cells. These and other data supported a model in which
      FKH1 and CLB5 modulated Sir2-4 chromatin and late-origin firing through opposing
      regulation of a common pathway.

PMID- 18045997
TI  - More time to taste. Focus on "variability in responses and temporal coding of
      tastants of similar quality in the nucleus of the solitary tract of the rat".

PMID- 18045996
TI  - Paxillin phosphorylation controls invadopodia/podosomes spatiotemporal
      organization.
AB  - In Rous sarcoma virus (RSV)-transformed baby hamster kidney (BHK) cells,
      invadopodia can self-organize into rings and belts, similarly to podosome
      distribution during osteoclast differentiation. The composition of individual
      invadopodia is spatiotemporally regulated and depends on invadopodia localization
      along the ring section: the actin core assembly precedes the recruitment of
      surrounding integrins and integrin-linked proteins, whereas the loss of the actin
      core was a prerequisite to invadopodia disassembly. We have shown that
      invadopodia ring expansion is controlled by paxillin phosphorylations on tyrosine
      31 and 118, which allows invadopodia disassembly. In BHK-RSV cells, ectopic
      expression of the paxillin mutant Y31F-Y118F induces a delay in invadopodia
      disassembly and impairs their self-organization. A similar mechanism is unraveled
      in osteoclasts by using paxillin knockdown. Lack of paxillin phosphorylation,
      calpain or extracellular signal-regulated kinase inhibition, resulted in similar
      phenotype, suggesting that these proteins belong to the same regulatory pathways.
      Indeed, we have shown that paxillin phosphorylation promotes Erk activation that
      in turn activates calpain. Finally, we observed that invadopodia/podosomes ring
      expansion is required for efficient extracellular matrix degradation both in BHK
      RSV cells and primary osteoclasts, and for transmigration through a cell
      monolayer.

PMID- 18045998
TI  - Dendritic properties of turtle pyramidal neurons.
AB  - The six-layered mammalian neocortex evolved from the three-layered paleocortex,
      which is retained in present-day reptiles such as the turtle. Thus the turtle
      offers an opportunity to examine which cellular and circuit properties are
      fundamental to cortical function. We characterized the dendritic properties of
      pyramidal neurons in different cortical regions of mature turtles, Pseudemys
      scripta elegans, using whole cell recordings and calcium imaging from the axon,
      soma, and dendrites in a slice preparation. The firing properties, in response to
      intrasomatic depolarization, resembled those previously recorded with sharp
      electrodes in this preparation. Somatic spikes led to active backpropagating high
      amplitude dendritic action potentials and intracellular calcium ion concentration
      ([Ca2+]i) changes at all dendritic locations, suggesting that both
      backpropagation and dendritic voltage-gated Ca2+ channels are primitive traits.
      We found no indication that Ca2+ spikes could be evoked in the dendrites, but
      fast Na+ spikes could be initiated there following intradendritic stimulation.
      Several lines of evidence indicate that fast, smaller-amplitude somatic spikes
      ("prepotentials") that are easily recorded in this preparation are generated in
      the axon. Most synaptically activated [Ca2+]i changes resulted from Ca2+ entry
      through voltage-gated channels. In some cells synaptic stimulation evoked a
      delayed Ca2+ wave due to release from internal stores following activation of
      metabotropic glutamate receptors. With some small differences these properties
      resemble those of pyramidal neurons in mammalian species. We conclude that spike
      backpropagation, dendritic Ca2+ channels, and synaptically activated Ca2+ release
      are primitive and conserved features of cortical pyramidal cells, and therefore
      likely fundamental to cortical function.

PMID- 18045999
TI  - Recovery of gaze stability during vestibular regeneration.
AB  - Many motion related behaviors, such as gaze stabilization, balance, orientation,
      and navigation largely depend on a properly functioning vestibular system. After
      vestibular insult, many of these responses are compromised but can return during
      the regeneration of vestibular receptors and afferents as is known to occur in
      birds, reptiles, and amphibians. Here we characterize gaze stability in pigeons
      to rotational motion during regeneration after complete bilateral vestibular loss
      via an ototoxic antibiotic. Immediate postlesion effects included severe head
      oscillations, postural ataxia, and total lack of gaze control. We found that
      these abnormal behaviors gradually subsided, and gaze stability slowly returned
      to normal function according to a temporal sequence that lasted several months.
      We also found that the dynamic recovery of gaze function during regeneration was
      not homogeneous for all types of motion. Instead high-frequency motion stability
      was first achieved, followed much later by slow movement stability. In addition,
      we found that initial gaze stability was established using almost exclusive head
      response components with little eye-movement contribution. However, that trend
      reversed as recovery progressed so that when gaze stability was complete, the eye
      component had increased and the head response had decreased to levels
      significantly different from that observed in normal birds. This was true even
      though the head-fixed VOR response recovered normally. Recovery of gaze stability
      coincided well with the three stage temporal sequence of morphologic regeneration
      previously described by our laboratory.

PMID- 18046000
TI  - What do synergies do? Effects of secondary constraints on multidigit synergies in
      accurate force-production tasks.
AB  - We used the framework of the uncontrolled manifold (UCM) hypothesis to explore
      changes in the structure of variability in multifinger force-production tasks
      when a secondary task was introduced. Healthy young subjects produced several
      levels of the total force by pressing with the four fingers of the hand on force
      sensors. The frame with the sensors rested on the table (Stable condition) or on
      a narrow supporting beam (Unstable conditions) that could be placed between
      different finger pairs. Most variance in the finger mode space was compatible
      with a fixed value of the total force across all conditions, whereas the patterns
      of sharing of the total force among the fingers were condition dependent. Moment
      of force was stabilized only in the Unstable conditions. The finger mode data
      were projected onto the UCM computed for the total force and subjected to
      principal component (PC) analysis. Two PCs accounted for >90% of the variance.
      The directions of the PC vectors varied across subjects in the Stable condition,
      whereas two "default" PCs were observed under the Unstable conditions. These
      observations show that different persons coordinate their fingers differently in
      force-production tasks. They converge on similar solutions when an additional
      constraint is introduced. The use of variable solutions allows avoiding a loss in
      accuracy of performance when the same elements get involved in another task. Our
      results suggest a mechanism underlying the principle of superposition suggested
      in a variety of human and robotic studies.

PMID- 18046001
TI  - Serotonergic modulation of afterhyperpolarization in a neuron that contributes to
      learning in the leech.
AB  - Modulation of afterhyperpolarization (AHP) represents an important mechanism by
      which excitability of a neuron can be regulated. In the leech brain,
      sensitization enhances excitability of the S-cell, an interneuron thought to play
      an important role in this form of nonassociative learning. This increase in
      excitability is serotonin (5-HT) dependent, but it is not known whether changes
      in AHP contribute to 5-HT-mediated enhancement of excitability. Therefore
      electrophysiological recordings and computational modeling were used to determine
      whether 5-HT enhances excitability via modulation of AHP. 5-HT reduced S-cell AHP
      and this decrease in the AHP corresponded with an increase in excitability.
      Little or no AHP is observed in the presence of Ca2+-free saline, suggesting the
      involvement of Ca2+-dependent K+ channels. Furthermore, AHP amplitude decreased
      following treatment with drugs (tubocurare and charybdotoxin) that block Ca2+
      dependent K+ channel activity. The S-cell also exhibits an afterdepolarization
      (ADP), which is usually masked by the AHP, and was inhibited by the Na+ channel
      blocker saxitoxin. A model of the S-cell AHP was constructed using two Ca2+
      dependent K+ currents and a Na+-driven ADP current. Reduction of the model
      conductances underlying the AHP to mimic the effects of 5-HT was sufficient to
      enhance excitability. These findings were confirmed in occlusion experiments in
      which pretreatment with tubocurare was able to block 5-HT-mediated decreases in
      mAHP levels and increases in excitability. These data show that modulation of S
      cell AHP can contribute to 5-HT-mediated increases in excitability and that the S
      cell afterpotential is due to the combined effects of AHP- and ADP-producing
      currents.

PMID- 18046002
TI  - Cortical and spinal modulation of antagonist coactivation during a submaximal
      fatiguing contraction in humans.
AB  - This study investigates the control mechanisms at the cortical and spinal levels
      of antagonist coactivation during a submaximal fatiguing contraction of the elbow
      flexors at 50% of maximal voluntary contraction (MVC). We recorded motor-evoked
      potentials in the biceps brachii and triceps brachii muscles in response to
      magnetic stimulation of the motor cortex (MEP) and corticospinal tract
      (cervicomedullary motor-evoked potentials--CMEPs), as well as the Hoffmann reflex
      (H-reflex) and maximal M-wave (Mmax) elicited by electrical stimulation of the
      brachial plexus, before, during, and after the fatigue task. The results showed
      that although the coactivation ratio did not change at task failure, the MVC
      torque produced by the elbow flexors declined by 48% (P < 0.01) with no change in
      MVC torque for the elbow extensors. While the MEP and CMEP areas (normalized to
      Mmax) of the biceps brachii increased ( approximately 50%) over the first 40% of
      the time to task failure and then plateaued, both responses in the triceps
      brachii increased ( approximately 150-180%) gradually throughout the fatigue
      task. In contrast to the monotonic increase in the MEP and CMEP of the antagonist
      muscles, the H-reflex of the triceps brachii exhibited a biphasic modulation,
      increasing during the first part of the contraction before declining subsequently
      to 65% of its initial value. Collectively, these results suggest that the level
      of coactivation during a fatiguing contraction is mediated by supraspinal rather
      than spinal mechanisms and involves differential control of agonist and
      antagonist muscles.

PMID- 18046003
TI  - Measurement and analysis of postsynaptic potentials using a novel voltage
      deconvolution method.
AB  - Accurate measurement of postsynaptic potential amplitudes is a central
      requirement for the quantification of synaptic strength, dynamics of short-term
      and long-term plasticity, and vesicle-release statistics. However, the
      intracellular voltage is a filtered version of the underlying synaptic signal and
      so a method of accounting for the distortion caused by overlapping postsynaptic
      potentials must be used. Here a voltage-deconvolution technique is demonstrated
      that defilters the entire voltage trace to reveal an underlying signal of well
      separated synaptic events. These isolated events can be cropped out and
      reconvolved to yield a set of isolated postsynaptic potentials from which voltage
      amplitudes may be measured directly-greatly simplifying this common task. The
      method also has the significant advantage of providing a higher temporal
      resolution of the dynamics of the underlying synaptic signal. The versatility of
      the method is demonstrated by a variety of experimental examples, including
      excitatory and inhibitory connections to neurons with passive membranes and those
      with activated voltage-gated currents. The deconvolved current-clamp voltage has
      many features in common with voltage-clamp current measurements. These
      similarities are analyzed using cable theory and a multicompartment cell
      reconstruction, as well as direct comparison to voltage-clamp experiments.

PMID- 18046004
TI  - Rhythmic constraints on hippocampal processing: state and phase-related
      fluctuations of synaptic excitability during theta and the slow oscillation.
AB  - Coordinated patterns of state-dependent synchronized oscillatory activity have
      been suggested to play differential roles in both the encoding and consolidation
      phases of hippocampal-dependent memories. Previous studies have concentrated on
      the mutually exclusive patterns of theta and sharp-wave/ripple activity because
      these were thought to be the only collective oscillatory patterns expressed in
      the hippocampus. Recently we (and others) have described a novel rhythmic
      activity expressed during anesthesia and deep sleep, the hippocampal slow
      oscillation (SO). In an attempt to describe the differential effects of theta and
      the SO on processing in the hippocampal circuit, we performed evoked potential
      analysis of two major pathways (the commissural and perforant) in urethan
      anesthetized rats across spontaneously expressed theta and SO states. We show
      that synaptic excitability was significantly enhanced in all pathways during the
      SO as compared with theta with the exception of the medial perforant path to the
      dentate gyrus, which showed greater excitability during theta. Furthermore,
      within each ongoing rhythm, there was a phase-dependent modulation of synaptic
      excitability. This occurred across all sites and similarly favored the falling
      phase (positive to negative) of both theta and the SO. Differential effects on
      the input, processing, and output circuitries of the hippocampus across mutually
      exclusive coordinated oscillatory patterns expressed during different states may
      be relevant for the staging of memory processes in the medial temporal lobe.

PMID- 18046005
TI  - Architecture of the mouse utricle: macular organization and hair bundle heights.
AB  - Hair bundles are critical to mechanotransduction by vestibular hair cells, but
      quantitative data are lacking on vestibular bundles in mice or other mammals.
      Here we quantify bundle heights and their variation with macular locus and hair
      cell type in adult mouse utricular macula. We also determined that macular
      organization differs from previous reports. The utricle has approximately 3,600
      hair cells, half on each side of the line of polarity reversal (LPR). A band of
      low hair cell density corresponds to a band of calretinin-positive calyces, i.e.,
      the striola. The relation between the LPR and the striola differs from previous
      reports in two ways. First, the LPR lies lateral to the striola instead of
      bisecting it. Second, the LPR follows the striolar trajectory anteriorly, but
      posteriorly it veers from the edge of the striola to reach the posterior margin
      of the macula. Consequently, more utricular bundles are oriented mediolaterally
      than previously supposed. Three hair cell classes are distinguished in calretinin
      stained material: type II hair cells, type ID hair cells contacting calretinin
      negative (dimorphic) afferents, and type IC hair cells contacting calretinin
      positive (calyceal) afferents. They differ significantly on most bundle measures.
      Type II bundles have short stereocilia. Type IC bundles have kinocilia and
      stereocilia of similar heights, i.e., KS ratios (ratio of kinocilium to
      stereocilia heights) approximately 1, unlike other receptor classes. In contrast
      to these class-specific differences, bundles show little regional variation
      except that KS ratios are lowest in the striola. These low KS ratios suggest that
      bundle stiffness is greater in the striola than in the extrastriola.

PMID- 18046006
TI  - Relative location of inhibitory synapses and persistent inward currents
      determines the magnitude and mode of synaptic amplification in motoneurons.
AB  - In some motoneurons, L-type Ca2+ channels that partly mediate persistent inward
      currents (PICs) have been estimated to be arranged in 50- to 200-microm-long
      discrete regions in the dendrites, centered 100 to 400 microm from the soma. As a
      consequence of this nonuniform distribution, the interaction between synaptic
      inputs to motoneurons and these channels may vary according to the distribution
      of the synapses. For instance, >93% of synapses from Renshaw cells have been
      observed to be located 65 to 470 microm away from the cell body of motoneurons.
      Our goal was to assess whether Renshaw cell synapses are distributed in a
      position to more effectively control the activation of the L-type Ca2+ channels.
      Using compartmental models of motoneurons with L-type Ca2+ channels distributed
      in 100-microm-long hot spots centered 100 to 400 microm away from the soma, we
      compared the inhibition generated by four distributions of inhibitory synapses:
      proximal, distal, uniform, and one based on the location of Renshaw cell synapses
      on motoneurons. Regardless of whether the synapses were activated tonically or
      transiently, in the presence of L-type Ca2+ channels, inhibitory synapses
      distributed according to the Renshaw cell synapse distribution generate the
      largest inhibitory currents. The effectiveness of a particular distribution of
      inhibitory synapses in the presence of PICs depends on their ability to
      deactivate the channels underlying PICs, which is influenced not only by the
      superposition between synapses and channels, but also by the distance away from
      the somatic voltage clamp.

PMID- 18046007
TI  - Multiple modes of amplification of synaptic inhibition to motoneurons by
      persistent inward currents.
AB  - The ability of inhibitory synaptic inputs to dampen the excitability of
      motoneurons is augmented when persistent inward currents (PICs) are activated.
      This amplification could be due to an increase in the driving potential of
      inhibitory synapses or the deactivation of the channels underlying PICs. Our goal
      was to determine which mechanism leads to the amplification of inhibitory inputs
      by PICs. To reach this goal, we measured inhibitory postsynaptic currents (IPSCs)
      in decerebrate cats during somatic voltage-clamp steps. These IPSCs were
      generated by tonic activation of Renshaw cells. The IPSCs exhibited a rapid rise
      and a slower decay to a plateau level. Activation of PICs always led to an
      increase in the peak of the IPSC, but the amount of decay after the peak of the
      IPSC was inversely related to the size of the IPSC. These results were replicated
      in simulations based on compartmental models of motoneurons incorporating
      distributions of Renshaw cell synapses based on anatomical observations, and L
      type calcium channels distributed as 100-microm-long hot spots centered 100 to
      400 microm away from the soma. For smaller IPSCs, amplification by PICs was due
      to an increase in the driving force of the inhibitory synaptic current. For
      larger IPSCs, amplification was caused by deactivation of the channels underlying
      PICs leading to a lesser decay of the IPSCs. As a result of this change in the
      time course of the IPSC, deactivation of the channels underlying PICs leads to a
      greater amplification of the total inhibitory synaptic current.

PMID- 18046008
TI  - Fine detail of neurovascular coupling revealed by spatiotemporal analysis of the
      hemodynamic response to single whisker stimulation in rat barrel cortex.
AB  - The spatial resolution of hemodynamic-based neuroimaging techniques, including
      functional magnetic resonance imaging, is limited by the degree to which neurons
      regulate their blood supply on a fine scale. Here we investigated the spatial
      detail of neurovascular events with a combination of high spatiotemporal
      resolution two-dimensional spectroscopic optical imaging, multichannel electrode
      recordings and cytochrome oxidase histology in the rodent whisker barrel field.
      After mechanical stimulation of a single whisker, we found two spatially distinct
      cortical hemodynamic responses: a transient response in the "upstream" branches
      of surface arteries and a later highly localized increase in blood volume
      centered on the activated cortical column. Although the spatial representation of
      this localized response exceeded that of a single "barrel," the spread of
      hemodynamic activity accurately reflected the neural response in neighboring
      columns rather than being due to a passive "overspill." These data confirm
      hemodynamics are capable of providing accurate "single-condition" maps of neural
      activity.

PMID- 18046009
TI  - Lamotrigine in pregnancy: clearance, therapeutic drug monitoring, and seizure
      frequency.
AB  - OBJECTIVE: To characterize the magnitude and course of alterations in total and
      free lamotrigine (LTG) clearance (Cl) during pregnancy and the postpartum period,
      to assess the impact of therapeutic drug monitoring (TDM) on seizure frequency,
      to determine the ratio to individual target LTG concentration that is associated
      with increased seizure risk, and to evaluate maternal postpartum toxicity.
      METHODS: A cohort of women were enrolled before conception or during pregnancy in
      this prospective, observational study. Visits occurred every 1 to 3 months with
      review of seizure and medication diaries, examination, and blood sampling. Total
      and free LTG Cls were calculated. Individualized target concentrations were used
      for TDM. The ratio to target concentration (RTC) was compared between patients
      with and without increased seizures. A receiver operating characteristic curve
      determined the threshold RTC that best predicts increased seizure frequency.
      RESULTS: Analysis of 305 samples in 53 pregnancies demonstrated increased total
      and free LTG Cl in all trimesters above nonpregnant baseline (p < 0.001), with
      peak increases of 94% and 89% in the third trimester. Free LTG Cl was higher in
      white compared with black women (p < 0.05). Increased seizure frequency (n = 36
      women with epilepsy) in the second trimester was associated with a lower RTC (p <
      0.001), and RTC < 0.65 was a significant predictor of seizure worsening. An
      empiric postpartum taper reduced the likelihood of maternal LTG toxicity (p <
      0.05) (n = 27). Newborn outcomes were similar to the general population (n = 52).
      CONCLUSIONS: These novel data contribute to a rational treatment plan and dosing
      paradigm for lamotrigine use during pregnancy, parturition, and the postpartum
      period.

PMID- 18046010
TI  - Trajectories of brain loss in aging and the development of cognitive impairment.
AB  - BACKGROUND: The use of volumetric MRI as a biomarker for assessing transitions to
      dementia presumes that more rapid brain loss marks the clinical transition from
      benign aging to mild cognitive impairment (MCI). The trajectory of this volume
      loss relative to the timing of the clinical transition to dementia has not been
      established. METHODS: The authors annually evaluated 79 healthy elderly subjects
      for up to 15 consecutive years with standardized clinical examinations and
      volumetric brain MRI assessments of ventricular volume. During the study period,
      37 subjects developed MCI. A mixed effects model with a change point modeled the
      pattern of brain volume loss in healthy aging compared with subjects diagnosed
      with MCI. RESULTS: The brain loss trajectory of subjects developing MCI during
      follow-up differed from healthy aging in a two-phase process. First, the annual
      rate of expansion of ventricular volume decreased with age; however, the annual
      rates of expansion were greater in those who developed cognitive impairment
      during follow-up compared with those who did not. Further, subjects who developed
      MCI had an acceleration of ventricular volume expansion approximately 2.3 years
      prior to clinical diagnosis of MCI. CONCLUSIONS: Ventricular expansion is faster
      in those developing mild cognitive impairment years prior to clinical symptoms,
      and eventually a more rapid expansion occurs approximately 24 months prior to the
      emergence of clinical symptoms. These differential rates of preclinical atrophy
      suggest that there are specific windows for optimal timing of introduction of
      dementia prevention therapies in the future.

PMID- 18046011
TI  - Methyl-beta-cyclodextrin improves fertilizing ability of C57BL/6 mouse sperm
      after freezing and thawing by facilitating cholesterol efflux from the cells.
AB  - Sperm cryopreservation provides an economical means of storing genetically
      engineered mouse strains in resource facilities. In general, relatively high
      fertilization rates are obtained for frozen/thawed sperm of the CBA/JN, DBA/2N,
      and C3H inbred strains and some F1 hybrid strains. However, the fertilization
      rate for frozen/thawed sperm of C57BL/6, which is the main strain of genetically
      engineered mice, remains very low. Therefore, it is necessary to establish an in
      vitro fertilization (IVF) method for cryopreserved C57BL/6 sperm that can obtain
      a high rate of fertilization after thawing. In the present study, we focused on
      the effects of methyl-beta-cyclodextrin (MBCD) on the fertilizing ability of
      frozen/thawed C57BL/6 sperm. Our results have shown that the highest
      fertilization rate for frozen/thawed sperm was obtained with MBCD at 1.0 mM for
      30 min (63.7% +/- 11.0%), but the effects were attenuated by long-term incubation
      for 120 min at 1.0 or 2.0 mM. The embryos with frozen/thawed sperm showed good
      developmental potential, and the offspring had normal fertility. The efflux of
      cholesterol from frozen/thawed sperm was increased by MBCD in a dose-dependent
      manner and occurred much earlier and to a greater extent than bovine serum
      albumin. The localization of cholesterol labeled by filipin in the sperm plasma
      membrane was drastically decreased by MBCD. In summary, we suggest that MBCD is
      useful for developing an IVF method for frozen/thawed C57BL/6 mouse sperm
      achieving a high fertilization rate, being involved in the capacity to sequester
      cholesterol from sperm membrane.

PMID- 18046012
TI  - Phylogenetic analysis and identification of pseudogenes reveal a progressive loss
      of zona pellucida genes during evolution of vertebrates.
AB  - Vertebrate eggs are surrounded by an extracellular matrix with similar functions
      and conserved individual components: the zona pellucida (ZP) glycoproteins. In
      mammals, chickens, frogs, and some fish species, we established an updated list
      of the ZP genes, studied the relationships within the ZP gene family using
      phylogenetic analysis, and identified ZP pseudogenes. Our study confirmed the
      classification of ZP genes in six subfamilies: ZPA/ZP2, ZPB/ZP4, ZPC/ZP3, ZP1,
      ZPAX, and ZPD. The identification of a Zpb pseudogene in the mouse genome, Zp1
      pseudogenes in the dog and bovine genomes, and Zpax pseudogenes in the human,
      chimpanzee, macaque, and bovine genomes showed that the evolution of ZP genes
      mainly occurs by death of genes. Our study revealed that the extracellular matrix
      surrounding vertebrate eggs contains three to at least six ZP glycoproteins.
      Mammals can be classified in three categories. In the mouse, the ZP is composed
      of three ZP proteins (ZPA/ZP2, ZPC/ZP3, and ZP1). In dog, cattle and, putatively,
      pig, cat, and rabbit, the zona is composed of three ZP proteins (ZPA/ZP2,
      ZPB/ZP4, and ZPC/ZP3). In human, chimpanzee, macaque, and rat, the ZP is composed
      of four ZP proteins (ZPA/ZP2, ZPB/ZP4, ZPC/ZP3, and ZP1). Our review provides new
      directions to investigate the molecular basis of sperm-egg recognition, a
      mechanism which is not yet elucidated.

PMID- 18046013
TI  - Short- and long-term effects of unilateral ovariectomy in sheep: causative
      mechanisms.
AB  - The mechanisms of ovulatory compensation following unilateral ovariectomy (ULO)
      are still not understood. In the present study, we investigated the short- and
      long-term effects of ULO in sheep using transrectal ovarian ultrasonography and
      hormone estimations made during the estrous cycle in which surgery was done, the
      estrous cycle 2 mo after surgery, and the 17-day period during the subsequent
      anestrus. The ULOs were done when a follicle in the first follicular wave of the
      cycle reached a diameter > or =5 mm, leaving at least one corpus luteum and one
      ovulatory-sized follicle in the remaining ovary. Ovulation rate per ewe was 50%
      higher in the ULO ewes compared with the control ewes at the end of the cycle
      during which surgery was performed, but it did not differ between groups at the
      end of the cycle, 2 mo later. This compensation of ovulation rate in ULO ewes was
      due to ovulation of follicles from the penultimate follicular wave in addition to
      those from the final wave of the cycle. Ovulation from multiple follicular waves
      appeared to be due to a prolongation of the static phase of the largest follicle
      of the penultimate wave of the cycle. Interestingly, the length of the static
      phase of waves was prolonged in ULO ewes compared with control ewes in every
      instance where the length of the static phase could be determined. Changes in
      follicular dynamics due to ULO were not associated with alterations in FSH and LH
      secretion. In conclusion, ovulatory compensation in ULO sheep involves ovulation
      from multiple follicular waves due to the lengthened static phase of ovulatory
      sized follicles. These altered antral follicular dynamics do not appear to be FSH
      or LH dependent. Further studies are required to examine the potential role of
      the nervous system in the enhancement of the life span of the ovulatory-sized
      follicles leading to ovulatory compensation by the unpaired ovary in ULO sheep.

PMID- 18046014
TI  - Hypoxia promotes luteal cell death in bovine corpus luteum.
AB  - Low oxygen caused by a decreasing blood supply is known to induce various
      responses of cells, including apoptosis. The present study was conducted to
      examine whether low-oxygen conditions (hypoxia) induce luteal cell apoptosis in
      cattle. Bovine midluteal cells incubated under hypoxia (3% O(2)) showed
      significantly more cell death than did those incubated under normoxia (20% O(2))
      at 24 and 48 h of culture, and had significantly lower progesterone (P4) levels
      starting at 8 h. Characteristic features of apoptosis, such as shrunken nuclei
      and DNA fragmentation, were observed in cells cultured under hypoxia for 48 h.
      Hypoxia increased the mRNA expressions of BNIP3 and caspase 3 at 24 and 48 h of
      culture. Hypoxia had no significant effect on the expressions of BCL2 and BAX
      mRNA. Hypoxia also increased BNIP3 protein, and activated caspase-3. Treatment of
      P4 attenuated cell death, caspase-3 mRNA expression, and caspase-3 activity under
      hypoxia. Overall results of the present study indicate that hypoxia induces
      luteal cell apoptosis by enhancing the expression of proapoptotic protein, BNIP3,
      and by activating caspase-3, and that the induction of apoptosis by hypoxia is
      partially caused by a decrease in P4 production. Because hypoxia suppresses P4
      synthesis in bovine luteal cells, we suggest that oxygen deficiency caused by a
      decreasing blood supply in bovine corpus luteum is one of the major factors
      contributing to both functional and structural luteolysis.

PMID- 18046015
TI  - Nutrient sensing by the early mouse embryo: hexosamine biosynthesis and glucose
      signaling during preimplantation development.
AB  - Although mouse oocytes and cleavage-stage embryos are unable to utilize glucose
      as a metabolic fuel, they have a specific requirement for a short exposure to
      glucose prior to compaction. The reason for this requirement has been unclear. In
      this study we confirm that cleavage-stage exposure to glucose is required for
      blastocyst formation and show that the absence of glucose between 18-64 h after
      hCG causes an irreversible decrease in cellular proliferation and an increase in
      apoptosis. More importantly, this glucose signals to activate expression of
      Slc2a3 transcript and SLC2A3 protein, a facilitative glucose transporter
      (previously known as GLUT3) associated with developmental competence and
      increased glucose uptake used to fuel blastocyst formation. Glucosamine could
      substitute for glucose in these roles, suggesting that hexosamine biosynthesis
      may be a nutrient-sensing mechanism involved in metabolic differentiation.
      Inhibition of the rate-limiting enzyme in this pathway, glutamine-fructose-6
      phosphate amidotransferase (GFPT), inhibited expression of the SLC2A3 transporter
      protein and blastocyst formation. Glucosamine, a substrate that enters this
      pathway downstream of GFPT, was able to overcome this inhibition and support
      SLC2A3 expression. These data suggest that early embryos rely on hexosamine
      biosynthesis as a glucose-sensing pathway to initiate metabolic differentiation.

PMID- 18046016
TI  - Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress
      and negatively regulating VEGF-induced pathways.
AB  - Recent studies have demonstrated that lymphocyte-derived microparticles (LMPs)
      impair endothelial cell function. However, no data currently exist regarding the
      contribution of LMPs in the regulation of angiogenesis. In the present study, we
      investigated the effects of LMPs on angiogenesis in vivo and in vitro and
      demonstrated that LMPs strongly suppressed aortic ring microvessel sprouting and
      in vivo corneal neovascularization. In vitro, LMPs considerably diminished human
      umbilical vein endothelial cell survival and proliferation in a concentration
      dependent manner. Mechanistically, the antioxidants U-74389G and U-83836E were
      partially protective against the antiproliferative effects of LMPs, whereas the
      NADPH oxidase (NOX) inhibitors apocynin and diphenyleneiodonium significantly
      abrogated these effects. Moreover, LMPs increased not only the expression of the
      NOX subunits gp91(phox), p22(phox), and p47(phox), but also the production of ROS
      and NOX-derived superoxide (O(2)(-)). Importantly, LMPs caused a pronounced
      augmentation in the protein expression of the CD36 antiangiogenic receptor while
      significantly downregulating the protein levels of VEGF receptor type 2 and its
      downstream signaling mediator, phosphorylated ERK1/2. In summary, LMPs potently
      suppress neovascularization in vivo and in vitro by augmenting ROS generation via
      NOX and interfering with the VEGF signaling pathway.

PMID- 18046017
TI  - Patterns of electrical propagation in the intact pregnant guinea pig uterus.
AB  - Previous studies have reported on propagation of individual spikes in isolated
      segments of the pregnant uterus, but there is no information on patterns of spike
      propagation in the intact organ. There is also no information on propagation of
      myometrial burst. The aim of this study was to record, at high resolution,
      patterns of propagation of electrical activities in the pregnant uterus. Sixteen
      timed-pregnant guinea pigs were euthanized at term, and their uteruses isolated.
      Fetuses were removed and replaced by an equal amount of Tyrode. A 240-electrode
      array was positioned at various locations along the organ, all signals were
      recorded simultaneously, and the electrical propagations were reconstructed. In
      the intact pregnant uterus at term, spikes propagated with high velocity in
      longitudinal (6.8 +/- 2.4 cm/s) and slower velocity in circular direction (2.8 +/
      1.0 cm/s; P < 0.01). Direction of propagation and frequency of activity were
      highly variable but showed similar patterns at the ovary or cervical end and
      along the anterior, posterior, and antimesometrial borders. Along mesometrium,
      spike propagation was sparse and fractionated. Migration of burst (0.6 +/- 0.4
      cm/s) was significantly much slower than that of individual spikes (P < 0.001).
      Initial burst activity was located at variable locations along the ovarial end of
      the antimesometrial border, while the latest excitation occurred at the cervical
      end (1.2 +/- 0.9 min). In conclusion, high resolution electrical mapping of the
      intact pregnant uterus reveals fundamental properties in spatial and temporal
      patterns of spike and burst propagation that determine the contraction of the
      organ.

PMID- 18046019
TI  - Chronobiological characterization of women with primary vasospastic syndrome:
      body heat loss capacity in relation to sleep initiation and phase of entrainment.
AB  - Women with primary vasospastic syndrome (VS), but otherwise healthy, exhibit a
      functional disorder of vascular regulation (main symptom: cold extremities) and
      often suffer from difficulties initiating sleep (DIS). Diverse studies have shown
      a close association between distal vasodilatation before lights off and a rapid
      onset of sleep. Therefore, we hypothesized that DIS in women with VS could be due
      to a reduced heat loss capacity in the evening, i.e., subjects are
      physiologically not ready for sleep. The aim of the study was to elucidate
      whether women having both VS and DIS (WVD) or not (controls) show different
      circadian characteristics (e.g., phase delay of the circadian thermoregulatory
      system with respect to the sleep-wake cycle). Healthy young women (n = 9 WVD and
      n = 9 control) completed a 40-h constant routine protocol (adjusted to habitual
      bedtime) before and after an 8-h sleep episode. Skin temperatures [off-line
      calculated as distal-proximal skin temperature gradient (DPG)] and core body
      temperature (CBT; rectal) were continuously recorded. Half-hourly saliva samples
      were collected for melatonin assay and subjective sleepiness was assessed on the
      Karolinska Sleepiness Scale (KSS). Compared with control, WVD showed no
      differences in habitual bed times, but a 1-h circadian phase delay of dim light
      melatonin onset (hours after lights on: WVD 14.6 +/- 0.3 h; control 13.5 +/- 0.2
      h; P = 0.01). Similar phase shifts were observed in CBT, DPG, and KSS ratings. In
      conclusion, WVD exhibit a phase delay of the endogenous circadian system with
      respect to their habitual sleep-wake cycle, which could be a cause of DIS.

PMID- 18046018
TI  - Zebrafish ae2.2 encodes a second slc4a2 anion exchanger.
AB  - The genome of zebrafish (Danio rerio) encodes two unlinked genes equally closely
      related to the SLC4A2/AE2 anion exchanger genes of mammals. One of these is the
      recently reported zebrafish ae2 gene (Shmukler BE, Kurschat CE, Ackermann GE,
      Jiang L, Zhou Y, Barut B, Stuart-Tilley AK, Zhao J, Zon LI, Drummond IA, Vandorpe
      DH, Paw BH, Alper SL. Am J Physiol Renal Physiol Renal Physiol 289: F835-F849,
      2005), now called ae2.1. We now report the structural and functional
      characterization of Ae2.2, the product of the second zebrafish Ae2 gene, ae2.2.
      The ae2.2 gene of zebrafish linkage group 24 encodes a polypeptide of 1,232 aa in
      length, sharing 70% amino acid identity with zebrafish Ae2.1 and 67% identity
      with mouse AE2a. Zebrafish Ae2.2 expressed in Xenopus oocytes encodes a 135-kDa
      polypeptide that mediates bidirectional, DIDS-sensitive Cl(-)/Cl(-) exchange and
      Cl(-)/HCO3(-) exchange. Ae2.2-mediated Cl(-)/Cl(-) exchange is cation
      independent, voltage insensitive, and electroneutral. Acute regulation of anion
      exchange mediated by Ae2.2 includes activation by NH4+ and independent inhibition
      by acidic intracellular pH and by acidic extracellular pH. In situ hybridization
      reveals low-level expression of Ae2.2 mRNA in zebrafish embryo, most notably in
      posterior tectum, eye, pharynx, epidermal cells, and axial vascular structures,
      without notable expression in the Ae2.1-expressing pronephric duct. Knockdown of
      Ae2.2 mRNA, of Ae2.1 mRNA, or of both with nontoxic or minimally toxic levels of
      N-morpholino oligomers produced no grossly detectable morphological phenotype,
      and preserved normal structure of the head and the pronephric duct at 24 h
      postfertilization.

PMID- 18046020
TI  - Calcium/calmodulin-dependent kinase II mediates NO-elicited PKG activation to
      participate in spinal reflex potentiation in anesthetized rats.
AB  - Calcium/calmodulin protein kinase (CaMK)-dependent nitric oxide (NO) and the
      downstream intracellular messenger cGMP, which is activated by soluble guanylate
      cyclase (sGC), are believed to induce long-term changes in efficacy of synapses
      through the activation of protein kinase G (PKG). The aim of this study was to
      examine the involvement of the CaMKII-dependent NO/sGC/PKG pathway in a novel
      form of repetitive stimulation-induced spinal reflex potentiation (SRP). A single
      pulse test stimulation (TS; 1/30 Hz) on the afferent nerve evoked a single action
      potential, while repetitive stimulation (RS; 1 Hz) induced a long-lasting SRP
      that was abolished by a selective Ca(2+)/CaMKII inhibitor, autocamtide 2-related
      inhibitory peptide (AIP). Such an inhibitory effect was reversed by a relative
      excess of nitric oxide synthase (NOS) substrate, L-arginine. In addition, the RS
      induced SRP was abolished by pretreatment with the NOS inhibitor, N(G)-nitro-L
      arginine-methyl ester (L-NAME). The sGC activator, protoporphyrin IX (PPIX),
      reversed the blocking effect caused by L-NAME. On the other hand, a sGC blocker,
      1H-[1, 2, 4]oxadiazolo[4, 3-alpha]quinoxalin-1-one (ODQ), abolished the RS
      induced SRP. Intrathecal applications of the membrane-permeable cGMP analog, 8
      bromoguanosine 3',5'-cyclic monophosphate sodium salt monohydrate (8-Br-cGMP),
      reversed the blocking effect on the RS-induced SRP elicited by the ODQ. Our
      findings suggest that a CaMKII-dependent NO/sGC/PKG pathway is involved in the RS
      induced SRP, which has pathological relevance to hyperalgesia and allodynia.

PMID- 18046021
TI  - Endothelial nitric oxide synthase is predominantly involved in angiotensin II
      modulation of renal vascular resistance and norepinephrine release.
AB  - Nitric oxide (NO) is mainly generated by endothelial NO synthase (eNOS) or
      neuronal NOS (nNOS). Recent studies indicate that angiotensin II generates NO
      release, which modulates renal vascular resistance and sympathetic
      neurotransmission. Experiments in wild-type [eNOS(+/+) and nNOS(+/+)], eNOS
      deficient [eNOS(-/-)], and nNOS-deficient [nNOS(-/-)] mice were performed to
      determine which NOS isoform is involved. Isolated mice kidneys were perfused with
      Krebs-Henseleit solution. Endogenous norepinephrine release was measured by HPLC.
      Angiotensin II dose dependently increased renal vascular resistance in all mice
      species. EC(50) and maximal pressor responses to angiotensin II were greater in
      eNOS(-/-) than in nNOS(-/-) and smaller in wild-type mice. The nonselective NOS
      inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 0.3 mM) enhanced
      angiotensin II-induced pressor responses in nNOS(-/-) and wild-type mice but not
      in eNOS(-/-) mice. In nNOS(+/+) mice, 7-nitroindazole monosodium salt (7-NINA;
      0.3 mM), a selective nNOS inhibitor, enhanced angiotensin II-induced pressor
      responses slightly. Angiotensin II-enhanced renal nerve stimulation induced
      norepinephrine release in all species. L-NAME (0.3 mM) reduced angiotensin II
      mediated facilitation of norepinephrine release in nNOS(-/-) and wild-type mice
      but not in eNOS(-/-) mice. 7-NINA failed to modulate norepinephrine release in
      nNOS(+/+) mice. (4-Chlorophrnylthio)guanosine-3', 5'-cyclic monophosphate (0.1
      nM) increased norepinephrine release. mRNA expression of eNOS, nNOS, and
      inducible NOS did not differ between mice strains. In conclusion, angiotensin II
      mediated effects on renal vascular resistance and sympathetic neurotransmission
      are modulated by NO in mice. These effects are mediated by eNOS and nNOS, but NO
      derived from eNOS dominates. Only NO derived from eNOS seems to modulate
      angiotensin II-mediated renal norepinephrine release.

PMID- 18046022
TI  - Clinical decisions. Management of stable coronary disease--polling results.

PMID- 18046023
TI  - Images in clinical medicine. A cobwebbing trabecular pattern.

PMID- 18046024
TI  - Bolstering the FDA's drug-safety authority.

PMID- 18046025
TI  - In defense of pharmacoepidemiology--embracing the yin and yang of drug research.

PMID- 18046026
TI  - Dengue and yellow fever--challenges for the development and use of vaccines.

PMID- 18046027
TI  - Eltrombopag for thrombocytopenia in patients with cirrhosis associated with
      hepatitis C.
AB  - BACKGROUND: Eltrombopag is a new, orally active thrombopoietin-receptor agonist
      that stimulates thrombopoiesis. We evaluated its ability to increase platelet
      counts and facilitate treatment for hepatitis C virus (HCV) infection in patients
      with thrombocytopenia associated with HCV-related cirrhosis. METHODS: Seventy
      four patients with HCV-related cirrhosis and platelet counts of 20,000 to less
      than 70,000 per cubic millimeter were randomly assigned to receive eltrombopag
      (30, 50, or 75 mg daily) or placebo daily for 4 weeks. The primary end point was
      a platelet count of 100,000 per cubic millimeter or more at week 4. Peginterferon
      and ribavirin could then be initiated, with continuation of eltrombopag or
      placebo for 12 additional weeks. RESULTS: At week 4, platelet counts were
      increased to 100,000 per cubic millimeter or more in a dose-dependent manner
      among patients for whom these data were available: in 0 of the 17 patients
      receiving placebo, in 9 of 12 (75%) receiving 30 mg of eltrombopag, in 15 of 19
      (79%) receiving 50 mg of eltrombopag, and in 20 of 21 (95%) receiving 75 mg of
      eltrombopag (P<0.001). Antiviral therapy was initiated in 49 patients (in 4 of 18
      patients receiving placebo, 10 of 14 receiving 30 mg of eltrombopag, 14 of 19
      receiving 50 mg of eltrombopag, and 21 of 23 receiving 75 mg of eltrombopag)
      while the administration of eltrombopag or placebo was continued. Twelve weeks of
      antiviral therapy, with concurrent receipt of eltrombopag or placebo, were
      completed by 36%, 53%, and 65% of patients receiving 30 mg, 50 mg, and 75 mg of
      eltrombopag, respectively, and by 6% of patients in the placebo group. The most
      common adverse event during the initial 4 weeks was headache; thereafter, the
      adverse events were those expected with interferon-based therapy. CONCLUSIONS:
      Eltrombopag therapy increases platelet counts in patients with thrombocytopenia
      due to HCV-related cirrhosis, thereby permitting the initiation of antiviral
      therapy. (ClinicalTrials.gov number, NCT00110799.)

PMID- 18046028
TI  - Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: The pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP)
      involves antibody-mediated platelet destruction and reduced platelet production.
      Stimulation of platelet production may be an effective treatment for this
      disorder. METHODS: We conducted a trial in which 118 adults with chronic ITP and
      platelet counts of less than 30,000 per cubic millimeter who had had relapses or
      whose platelet count was refractory to at least one standard treatment for ITP
      were randomly assigned to receive the oral thrombopoietin-receptor agonist
      eltrombopag (30, 50, or 75 mg daily) or placebo. The primary end point was a
      platelet count of 50,000 or more per cubic millimeter on day 43. RESULTS: In the
      eltrombopag groups receiving 30, 50, and 75 mg per day, the primary end point was
      achieved in 28%, 70%, and 81% of patients, respectively. In the placebo group,
      the end point was achieved in 11% of patients. The median platelet counts on day
      43 for the groups receiving 30, 50, and 75 mg of eltrombopag were 26,000,
      128,000, and 183,000 per cubic millimeter, respectively; for the placebo group
      the count was 16,000 per cubic millimeter. By day 15, more than 80% of patients
      receiving 50 or 75 mg of eltrombopag daily had an increased platelet count.
      Bleeding also decreased during treatment in these two groups. The incidence and
      severity of adverse events were similar in the placebo and eltrombopag groups.
      CONCLUSIONS: Eltrombopag increased platelet counts in a dose-dependent manner in
      patients with relapsed or refractory ITP. (ClinicalTrials.gov number,
      NCT00102739.)

PMID- 18046029
TI  - Patent foramen ovale and cryptogenic stroke in older patients.
AB  - BACKGROUND: Studies to date have shown an association between the presence of
      patent foramen ovale and cryptogenic stroke in patients younger than 55 years of
      age. This association has not been established in patients 55 years of age or
      older. METHODS: We prospectively examined 503 consecutive patients who had had a
      stroke, and we compared the 227 patients with cryptogenic stroke and the 276
      control patients with stroke of known cause. We examined the prevalences of
      patent foramen ovale and of patent foramen ovale with concomitant atrial septal
      aneurysm in all patients, using transesophageal echocardiography. We also
      compared data for the 131 younger patients (< 55 years of age) and those for the
      372 older patients (> or = 55 years of age). RESULTS: The prevalence of patent
      foramen ovale was significantly greater among patients with cryptogenic stroke
      than among those with stroke of known cause, for both younger patients (43.9% vs.
      14.3%; odds ratio, 4.70; 95% confidence interval [CI], 1.89 to 11.68; P<0.001)
      and older patients (28.3% vs. 11.9%; odds ratio, 2.92; 95% CI, 1.70 to 5.01;
      P<0.001). Even stronger was the association between the presence of patent
      foramen ovale with concomitant atrial septal aneurysm and cryptogenic stroke, as
      compared with stroke of known cause, among both younger patients (13.4% vs. 2.0%;
      odds ratio, 7.36; 95% CI, 1.01 to 326.60; P=0.049) and older patients (15.2% vs.
      4.4%; odds ratio, 3.88; 95% CI, 1.78 to 8.46; P<0.001). Multivariate analysis
      adjusted for age, plaque thickness, and presence or absence of coronary artery
      disease and hypertension showed that the presence of patent foramen ovale was
      independently associated with cryptogenic stroke in both the younger group (odds
      ratio, 3.70; 95% CI, 1.42 to 9.65; P=0.008) and the older group (odds ratio,
      3.00; 95% CI, 1.73 to 5.23; P<0.001). CONCLUSIONS: There is an association
      between the presence of patent foramen ovale and cryptogenic stroke in both older
      patients and younger patients. These data suggest that paradoxical embolism is a
      cause of stroke in both age groups.

PMID- 18046030
TI  - Clinical practice. Late-life depression.

PMID- 18046031
TI  - Computed tomography--an increasing source of radiation exposure.

PMID- 18046032
TI  - Images in clinical medicine. Paradoxical embolism--thrombus in a patent foramen
      ovale.

PMID- 18046033
TI  - Case records of the Massachusetts General Hospital. Case 37-2007. A 47-year-old
      man with left ventricular dysfunction after heart transplantation.

PMID- 18046034
TI  - Immune thrombocytopenic purpura--from agony to agonist.

PMID- 18046035
TI  - Continuous-flow ventricular assist device.

PMID- 18046036
TI  - Progesterone and preterm birth.

PMID- 18046037
TI  - Isolated systolic hypertension in the elderly.

PMID- 18046038
TI  - Medical mystery: an unusual complication of colonoscopy--the answer.

PMID- 18046039
TI  - Compounded colistimethate as possible cause of fatal acute respiratory distress
      syndrome.

PMID- 18046040
TI  - Case 27-2007: Intrauterine fetal death.

PMID- 18046041
TI  - Violence against girls provokes girls' violence: from private injury to public
      harm.
AB  - Young women adjudicated delinquent in juvenile court report suffering inordinate
      amounts of emotional, physical, and sexual trauma in early childhood and
      adolescence. In addition, adolescent girls' arrests for violent crimes rose
      dramatically in the 1990s. This article explores the relationship between those
      two factors. Drawing from interviews with court-involved girls, this article
      highlights two contexts in which girls committed aggressive offenses: an
      incidence of intimate violence in a lesbian relationship and a stabbing in self
      defense against sexual assault. I argue that the trauma witnessed and experienced
      from prior childhood and adolescent injuries--much of it experienced in private-
      contributed to girls' coming to the attention of public authorities.

PMID- 18046042
TI  - Patriarchy matters: toward a gendered theory of teen violence and victimization.
AB  - This article explores the role that the sex-gender system plays in shaping both
      the violence and victimization of girls. Taking first the issue of girls'
      violence, the article argues that steep increases in girls' arrests are not the
      product of girls becoming more like boys. Instead, forms of girls' minor violence
      that were once ignored are now being criminalized. Shifting gears, the article
      explores how "gender-neutral" relabeling of girls' victimization in schools, a
      site of much violence against girls, is extremely problematic. Renaming "sexual
      harassment" as "bullying" tends to psychopathologize gender violence while
      simultaneously stripping girl victims of powerful legal rights and remedies. To
      illustrate this latter point, a "model" antibullying program, The Bullying
      Prevention Program, is reviewed. Offering a one-size-fits-all view of bullying,
      it assumes all bullying can be approached psychologically or relationally,
      thereby minimizing the structural underpinnings of such behavior.

PMID- 18046043
TI  - Dating conflicts: rethinking dating violence and youth conflict.
AB  - Dating couples are tied to each other's friends who have expectations about
      dating, such as who constitutes an acceptable date and how to balance friendship
      and dating. We explore the place of friends in dating conflicts (i.e., conflicts
      and violence associated with heterosexual teen dating) and ask: (a) How are
      friends implicated in teen dating/violence not only as targets or confidants, but
      also as participants in conflict that stems from their friends' relationships,
      and (b) in what ways do dating conflicts conserve or challenge the power of
      gender and sexual conformity that underlies heterosexual dating and dating
      violence?

PMID- 18046044
TI  - Violence and desire in Beijing: a young Chinese woman's strategies of resistance
      in father daughter incest and dating relationships.
AB  - In Mainland China, there is a lack of public awareness of and systematic research
      on dating violence and incest. This article fills a gap in the research in this
      area by examining a woman's lived experience of father-daughter incest and dating
      violence. The article adopts the standpoint of third-wave feminists and
      highlights women's agency and resistance to abuse. Meng Xi, the subject of the
      case study in this article, is regarded as a "survivor" rather than a "victim,"
      and her various strategies of resistance--in particular, how she talks about her
      body and linghun (intelligence soul), and uses the two as sites of resistance-
      are examined. The article sheds light on the desire and sexuality of women in
      contemporary China, and especially the struggle between spiritual and material
      pursuits.

PMID- 18046045
TI  - Massive but selective cytokine dysregulation in the colon of IL-10-/- mice
      revealed by multiplex analysis.
AB  - IL-10-deficient mice develop enterocolitis due to a failure of cytokine
      regulation; however, the full scope of that response remains poorly defined.
      Using multiplex analysis to quantify the activity of 23 regulatory and effector
      cytokines produced by colonic leukocytes, we demonstrate a vast dysregulation
      process of 18 cytokines in IL-10-/- mice from 7 to 27 weeks of age. Of those, IL
      12p40, IL-6, granulocyte macrophage colony-stimulating factor, IFN-gamma, IL-13
      and monocyte chemoattractant protein-1 (MCP-1) had the highest single
      correlations with pathology (r = 0.7766-0.7016). Importantly, there were strong
      associations (r = 0.7071-0.9074) between those cytokines and as many as 10
      additional cytokines, indicating a high degree of cytokine complexity as disease
      progressed. IL-17 was notable in that it was produced at high levels by colonic
      leukocytes from IL-10-/- mice with pathology ranging from mild to severe, though
      it was not produced by healthy IL-10-/- mice lacking pathology. Tumor necrosis
      factor alpha (TNFalpha) by itself displayed only a modest association with
      pathology (r = 0.6340), ranking sixth lowest, though it cross-correlated strongly
      with the synthesis of 12 other cytokines, implying that the destructive effects
      associated with TNFalpha may be due to interactions of multiple cytokine
      activities. IL-23 expression did not correlate with pathology, possibly
      suggesting that IL-23 is involved in the initiation but not the perpetuation of
      inflammation. Four cytokines (IL-2, IL-3, IL-4 and IL-5) remained negative in IL
      10-/- mice, demonstrating that cytokine dysregulation was not universal. These
      findings emphasize the need to better understand cytokine networks in chronic
      inflammation and they provide a rationale for combining immunotherapies in the
      treatment of intestinal inflammation.

PMID- 18046046
TI  - Conditionally immortalized white preadipocytes: a novel adipocyte model.
AB  - This study describes a novel approach to generate conditionally immortalized
      preadipocyte cell lines from white adipose tissue (IMWAT) that can be induced to
      differentiate into white adipocytes even after expansion in culture. Such
      adipocytes express markers of white fat such as peroxisome proliferator-activated
      receptor gamma and aP2 but not brown fat markers, have an intact insulin
      signaling pathway, and express proinflammatory cytokines. They can be readily
      transduced with adenoviral vectors, allowing them to be used to investigate the
      consequences of the depletion of specific adipocyte factors using short hairpin
      RNA. This approach has been used to study the effect of reduced expression of the
      nuclear receptor corepressor receptor interacting protein 140 (RIP140), a
      regulator of adipocyte function. The depletion of RIP140 results in changes in
      metabolic gene expression that resemble those in adipose tissue of the RIP140
      null mouse. Thus, IMWAT cells provide a novel model for adipocytes that are
      derived from preadipocytes rather than fibroblasts and provide an alternative
      system to primary preadipocytes for the investigation of adipocyte function.

PMID- 18046048
TI  - Pharmacokinetics and pharmacodynamics of oral testosterone enanthate plus
      dutasteride for 4 weeks in normal men: implications for male hormonal
      contraception.
AB  - Oral administration of testosterone enanthate (TE) and dutasteride increases
      serum testosterone and might be useful for male hormonal contraception. To
      ascertain the contraceptive potential of oral TE and dutasteride by determining
      the degree of gonadotropin suppression mediated by 4 weeks of oral TE plus
      dutasteride, 20 healthy young men were randomly assigned to 4 weeks of either 400
      mg oral TE twice daily or 800 mg oral TE once daily in a double-blinded,
      controlled fashion at a single site. All men received 0.5 mg dutasteride daily.
      Blood for measurement of serum luteinizing hormone (LH), follicle-stimulating
      hormone (FSH), testosterone, dihydrotesterone (DHT), and estradiol was obtained
      prior to treatment, weekly during treatment, and 1, 2, 4, 8, 12, 13, 14, 16, 20,
      and 24 hours after the morning dose on the last day of treatment. FSH was
      significantly suppressed throughout treatment with 800 mg TE once daily and after
      4 weeks of treatment with 400 mg TE twice daily. LH was significantly suppressed
      after 2 weeks of treatment with 800 mg TE, but not with 400 mg TE. Serum DHT was
      suppressed and serum estradiol increased during treatment in both groups. High
      density lipoprotein cholesterol was suppresed during treatment, but liver
      function tests, hematocrit, creatinine, mood, and sexual function were
      unaffected. The administration of 800 mg oral TE daily combined with dutasteride
      for 28 days significantly suppresses gonadotropins without untoward side effects
      and might have utility as part of a male hormonal contraceptive regimen.

PMID- 18046049
TI  - In vivo application of histone deacetylase inhibitor trichostatin-a impairs
      murine male meiosis.
AB  - In vivo application of histone deacetylase (HDAC) inhibitor trichostatin-A (TSA)
      in mice results in male infertility. To get more insight into the mechanisms
      underlying this phenomenon, we performed a genome-wide expression analysis and
      investigated HDAC activity and degree of histone H3 and H4 acetylation in murine
      testes after TSA treatment. A significant decrease in HDAC activity and a weak
      increase in histone acetylation could be demonstrated at 2.5, 5.0, and 7.5 hours
      after TSA application. Gene expression analysis revealed 507 significantly
      regulated genes. Transcripts expressed in the somatic cells of the testis
      (Sertoli, Leydig, peritubular cells, and testis macrophages) or extratubular
      matrix were regulated as early as 2.5 hours after TSA application, whereas very
      few meiosis-specific genes were modulated after TSA treatment. In addition,
      members of the p53-noxa-caspase-3 proapoptotic pathway were regulated early.
      Applying in-situ hybridization, caspase-3-mRNA was found only in apoptotic
      spermatocytes, whereas TRP53/p53- and PMAIP1/noxa-mRNA could be demonstrated in
      spermatogonia and spermatocytes. Our data suggest that TSA impaired male meiosis,
      possibly through an indirect mechanism implicating somatic cells of the testis.

PMID- 18046050
TI  - Adenosine triphosphate production by bovine spermatozoa and its relationship to
      semen fertilizing ability.
AB  - This article's objectives are to investigate the relationship between adenosine
      triphosphate (ATP) production (oxidative phosphorylation and glycolysis) and
      fertility of bovine spermatozoa, determine the proportion of oxygen consumption
      devoted to proton leak and that due to nonmitochondrial processes, and discover
      whether freeze/thawing affects sperm oxygen consumption. Oxygen consumption of
      bovine spermatozoa was measured using a standard Clark electrode and, for the
      first time, in an Oxygen Biosensor System (OBS). Total ATP formation by bovine
      spermatozoa was calculated from the oxygen consumption and lactate production
      (glycolysis) by the same spermatozoa sample. ATP production varied from 1.99 to
      8.09 mumol ATP per 10(8) spermatozoa per hour; glycolysis accounted for 16% to
      38% of ATP. Nonmitochondrial oxygen consumption could not be detected in bovine
      spermatozoa using these methods. A significant proportion (16%-43%) of oxygen
      consumption was insensitive to oligomycin and was due to "proton leak." There was
      no significant difference between oxygen consumption of frozen/thawed and fresh
      spermatozoa for 2 of the 3 bulls tested. However, oxygen consumption of
      frozen/thawed spermatozoa was significantly higher (P < .05) than fresh
      spermatozoa for the third bull. When ZO(2) of frozen/thawed spermatozoa from 20
      bulls was compared with their 49 day nonreturn rates (NRRs), oxygen consumption
      was correlated positively with NRR (ie, fresh spermatozoa with a higher ZO(2)
      were more fertile). Moreover, total ATP production correlated with NNR better
      than ZO(2). Bulls with a lower NRR produce spermatozoa that are susceptible to
      damage during the freeze/thawing process, causing an increase in ZO(2), possibly
      due to mitochondrial membrane damage resulting in more energy being expended in
      maintaining the proton gradient, or capacitation-like changes causing
      hyperactivation. Oxygen consumption measured in the OBS may be useful in
      assessing bovine sperm fertility.

PMID- 18046051
TI  - Coculture of spermatogonia with somatic cells in a novel three-dimensional soft
      agar-culture-system.
AB  - Isolation and culture of spermatogonial stem cells (SSCs) has become an approach
      to study the milieu and the factors controlling their expansion and
      differentiation. Traditional conventional cell culture does not mimic the complex
      situation in the seminiferous epithelium providing a basal, intraepithelial, and
      adluminal compartment to the developing male germ cells. SSCs are located in
      specific stem cell niches whose features and functional parameters are thus far
      poorly understood. It was the aim of this study to isolate SSCs and to explore
      their expansion and differentiation potential in a novel three-dimensional Soft
      Agar-Culture-System (SACS). This system provides three-dimensional structural
      support and multiple options for manipulations through the addition of factors,
      cells, or other changes. The system has revolutionized research on blood stem
      cells by providing a tool for clonal analysis of expanding and differentiating
      blood cell lineages. In our studies, SSCs are enriched using Gfralpha-1 as a
      specific surface marker and magnetic-activated cell sorting as a separation
      approach. At termination of the culture, we determined the type and number of
      germ cells obtained after the first 24 hours of culture. We also determined cell
      types and numbers in expanding cell clones of differentiating germ cells during
      the subsequent 15 days of culture. We analyzed a supportive effect of somatic
      cell lineages added to the solid part of the culture system. We conclude that our
      enrichment and culture approach is highly useful for exploration of SSC expansion
      and have found indications that the system supports differentiation up to the
      level of postmeiotic germ cells.

PMID- 18046052
TI  - Nutritional adequacy of different menu settings in elite Spanish adolescent
      soccer players.
AB  - The article describes a study that evaluated the adequacy of 2 different menu
      settings in a group of elite adolescent Spanish soccer players. Five-day food
      intake was assessed on 2 occasions, while athletes were consuming a flexible
      "buffet-style" diet (B; n = 33) and a fixed "menu-style" diet (M; n = 29). For
      all principal meals of the day food weighing was performed, and snacks were
      recorded by self-report. M provided significantly higher total energy and
      carbohydrate intakes than B. Breakfast and snacks both provided more energy in M.
      Calories obtained from fat were excessive in both settings. Calcium and vitamin D
      were below recommendations in B but not in M. Fiber, magnesium, folate, vitamin
      A, and vitamin E intake fell below recommended values in both settings. M
      provided significantly greater quantities of magnesium and vitamins D and E. Both
      feeding options were far from optimal in satisfying current scientifically based
      recommendations for active adolescents.

PMID- 18046053
TI  - Effect of Red Bull energy drink on repeated Wingate cycle performance and bench
      press muscle endurance.
AB  - The purpose of this study was to determine the effects of Red Bull energy drink
      on Wingate cycle performance and muscle endurance. Healthy young adults (N = 15,
      11 men, 4 women, 21 +/- 5 y old) participated in a crossover study in which they
      were randomized to supplement with Red Bull (2 mg/kg body mass of caffeine) or
      isoenergetic, isovolumetric, noncaffeinated placebo, separated by 7 d. Muscle
      endurance (bench press) was assessed by the maximum number of repetitions over 3
      sets (separated by 1-min rest intervals) at an intensity corresponding to 70% of
      baseline 1-repetition maximum. Three 30-s Wingate cycling tests (load = 0.075
      kp/kg body mass), with 2 min recovery between tests, were used to assess peak and
      average power output. Red Bull energy drink significantly increased total bench
      press repetitions over 3 sets (Red Bull = 34 +/- 9 vs. placebo = 32 +/- 8, P
      %%%lt; 0.05) but had no effect on Wingate peak or average power (Red Bull = 701
      +/- 124 W vs. placebo = 700 +/- 132 W, Red Bull = 479 +/- 74 W vs. placebo = 471
      +/- 74 W, respectively). Red Bull energy drink significantly increased upper body
      muscle endurance but had no effect on anaerobic peak or average power during
      repeated Wingate cycling tests in young healthy adults.

PMID- 18046054
TI  - Carbohydrate-gel supplementation and endurance performance during intermittent
      high-intensity shuttle running.
AB  - The aim of this study was to investigate the effects of a carbohydrate (CHO) gel
      on performance after prolonged intermittent high-intensity shuttle running. Seven
      male soccer players performed 2 exercise trials, 7 d apart. On each occasion,
      participants completed five 15-min periods of intermittent variable-speed
      running, interspersed with periods of walking (Part A), followed by an
      intermittent run to exhaustion (Part B). Participants consumed either a CHO gel
      or placebo (PLA) immediately before exercise (0.89 mL/kg body mass [BM]) and
      every 15 min thereafter (0.35 mL/kg BM). In addition, water was consumed at a
      rate of 5 mL/kg BM before and 2 mL/kg BM every 15 min during exercise. Blood
      glucose levels were higher (P < 0.05) at 15, 30, and 60 min of exercise and at
      exhaustion in CHO than in PLA. During Part B, run time to exhaustion was longer
      (P < 0.05) in the CHO trial (CHO 6.1 +/- 1.3 min vs. PLA 4.2 +/- 1.2 min). These
      results indicate that ingesting a CHO gel, along with water, improves performance
      after prolonged intermittent running in healthy male subjects, possibly by
      maintaining blood glucose levels during exercise.

PMID- 18046055
TI  - The effects of nutritional supplementation throughout an endurance run on leucine
      kinetics during recovery.
AB  - This study determined the effect of nutritional supplementation throughout
      endurance exercise on whole-body leucine kinetics (leucine rate of appearance
      [Ra], oxidation [Ox], and nonoxidative leucine disposal [NOLD]) during recovery.
      Five trained men underwent a 2-h run at 65% VO(2max), during which a carbohydrate
      (CHO), mixed protein-carbohydrate (milk), or placebo (PLA) drink was consumed.
      Leucine kinetics were assessed during recovery using a primed, continuous
      infusion of 1-13C leucine. Leucine Ra and NOLD were lower for milk than for PLA.
      Ox was higher after milk-supplemented exercise than after CHO or PLA. Although
      consuming milk during the run affected whole-body leucine kinetics, the benefits
      of such a practice for athletes remain unclear. Additional studies are needed to
      determine whether protein supplementation during exercise can optimize protein
      utilization during recovery.

PMID- 18046056
TI  - Caffeine-induced changes in cardiovascular function during resistance training.
AB  - Caffeine (CAF) exerts a pressor effect both at rest and during exercise, as blood
      pressure is higher than with placebo. The effect of acute CAF ingestion combined
      with intense resistance training on cardiovascular function is unknown, however.
      The primary aim of the study was to examine changes in cardiovascular function
      after completion of fatiguing bench-press and leg-press exercise after CAF or
      placebo ingestion. Twenty-two resistance-trained men ingested CAF (6 mg/kg) or
      placebo 1 h preexercise in a randomized, double-blind crossover design. They
      refrained from CAF intake and strenuous exercise 48 and 24 h pretrial,
      respectively. Heart rate and blood pressure were measured preexercise. After a
      standardized warm-up, 1-repetition-maximum (1-RM) on the barbell bench press and
      leg press was tested. When it had been determined, a load equivalent to 60% of 1
      RM was placed on the bar, and the subject completed repetitions to failure.
      Measurements of heart rate and blood pressure were immediately completed, and
      mean arterial pressure and rate-pressure product were calculated. Results showed
      significant (P < 0.05) increases in heart rate (+ 10 beats/min), systolic blood
      pressure (+ 8-10 mmHg), and rate-pressure product with acute CAF ingestion versus
      placebo. No change (P > 0.05) in diastolic blood pressure across time or
      treatment was shown. To prevent elevated blood pressure and potential enhanced
      risk of heart disease, CAF intake should be monitored in at-risk men who
      participate in resistance training.

PMID- 18046057
TI  - Influence of carbohydrate, intense exercise, and rest intervals on hormonal and
      oxidative changes.
AB  - This study compared effects of carbohydrate (CHO) and rest on oxidative stress
      during exercise. Cyclists (N = 12) completed 4 randomized trials at 64% Wattsmax
      under 2 conditions (continuous cycling for 2 h [C] and cycling with 3-min rest
      every 10 min for 2.6 h [R]). Subjects cycled under each condition while receiving
      6% CHO and placebo (PLA). CHO and PLA were given preexercise (12 mL/kg) and
      during exercise (4 mL x kg(-1) x 15 min(-1)). Blood was collected preexercise,
      postexercise, and 1 h postexercise and assayed for F2-isoprostanes,
      hydroperoxides (LH), nitrite, antioxidant capacity, glucose, insulin, cortisol,
      and epinephrine. F2-isoprostanes and LH were lower in CHO. Glucose, cortisol, and
      epinephrine exhibited significant effects, with postexercise levels of glucose
      higher and cortisol and epinephrine lower in CHO during the R condition. This
      pattern was identical in the C condition (21). Oxidative stress during cycling
      was unaffected by use of short rest intervals but was diminished by CHO.

PMID- 18046058
TI  - Systematic review on use of a handheld indirect calorimeter to assess energy
      needs in adults and children.
AB  - With the number of individuals becoming overweight or obese, health care
      professionals are in need of accurate, reliable, and convenient tools to help
      personalize weight-loss programs. Recently, a new handheld indirect calorimeter
      (i.e., MedGem/BodyGem; also know as "Gem") was introduced as a convenient way to
      assess resting metabolic rate (RMR) to determine daily energy needs. Several
      validation and comparison studies were conducted to determine whether the Gem
      device is accurate and reliable, and results from these studies are mixed.
      Fourteen human studies (12 adult, 2 pediatric) were conducted, and 12 met the
      established criteria for this review. In all Douglas-bag (DB; n = 4) validation
      studies, the Gem device was not significantly different than the DB (mean
      difference adult +/-1%, pediatric +/-1%). The intraclass reliability of the Gem
      ranged from 0.97 to 0.98, and the interclass reliability to the DB ranged from
      0.91 to 0.97. Although few (n = 2) studies have demonstrated that the Gem device
      measures RMR significantly lower (-8.2% to 15.1%) than traditional metabolic
      carts, it performs very comparably (RMR values 0.1-4.0%, interclass reliability
      0.76-0.92) to traditional metabolic carts in most (n = 6) of the comparison
      studies. Based on these data, the Gem device is a valid and reliable indirect
      calorimeter for energy assessment in most adults and children.

PMID- 18046059
TI  - Differential expression of autophagy in Hodgkin lymphoma cells treated with
      various anti-cancer drugs.
AB  - AIM: autophagy is a pivotal physiological process for survival during starvation,
      differentiation and normal growth control. It is defined as the process of
      sequestrating cytoplasmic proteins or even entire organelles into the lytic
      compartment (lysosome/vacuole). This study investigates the expression of
      autophagy in Hodgkin lymphoma cells treated with various anti-cancer drugs.
      METHODS: Hodgkin's lymphoma cells (HD-My-Z cells) were cultured with various anti
      cancer drugs, such as bleomycin, adriamycin, gemcitabine and paclitaxel.
      Autophagy was detected by fluorescent pattern of light chain 3(LC3) proteins and
      the apoptotic cell death was determined by annexin V binding. RESULTS: autophagy
      was detected in HD-My-Z cells treated with gemcitabine, but not with bleomycin,
      adriamycin and paclitaxel. Adriamycin exhibited the strongest cytotoxic action,
      and the cytotoxic action of bleomycin and gemcitabine was less marked compared
      with adriamycin. Paclitaxel did not cause significant cell death in the cells.
      CONCLUSION: autophagy was differentially expressed in Hodgkin lymphoma cells
      treated with anti-cancer drugs and the expression did not correspond to the
      apoptotic cell death.

PMID- 18046060
TI  - Helicobacter pylori infection: prevalence in chronic urticaria patients and
      incidence of autoimmune urticaria (study in Dr. Cipto Mangunkusumo Hospital,
      Jakarta).
AB  - AIM: To determine the prevalence of Hp infection in patients with chronic
      urticaria (CU) and to evaluate the result of autologous serum skin test (ASST) in
      CU patients with Hp infections. METHODS: In this cross-sectional study, 16
      patients with chronic urticaria and 16 non-urticaria volunteers were investigated
      (matched for age and sex). All subjects were examined for Hp infection with the
      13C-urea breath test. Autologous serum skin test was performed in patients with
      proven Hp infection. RESULTS: Helicobacter pylori was detected in 12.5% of
      patients and 0% of the control group. There was no significant difference between
      the two groups (p = 0.484 using Fisher exact test). Autologous serum skin test
      was positive in 1 of 2 CU patients with Hp infection. CONCLUSION: In this study,
      there was no significant difference in the seroprevalence of Hp infection between
      CU patients and controls. Autologous serum skin test was positive in 1 of 2 CU
      patients with Hp infection.

PMID- 18046061
TI  - Correlation between free thyroxin levels and left ventricular ejection fraction
      in Graves' disease (preliminary study).
AB  - AIM: to determine the correlation between free thyroid hormone level and left
      ventricular ejection fraction in newly diagnosed Graves' patients. METHODS: this
      is a preliminary study with an initial cross-sectional design using free
      thyroxine level as a parameter of thyroid hormone state and left ventricular
      ejection fraction (LVEF) as a parameter of left ventricular systolic function.
      Free thyroxine level was measured in the laboratory and the LVEF was assessed by
      Simpson's methods of echocardiography study. RESULTS: ten patients (7 men and 3
      women; age 18-52 years old) were studied. Their average of fT4 was 5.75 (SD 0.96)
      ng/dL and their average of LVEF was 70.57 (SD 4.50)%. There was positive
      correlation coefficient between free thyroxine level and left ventricular
      ejection fraction (r=0.711, p=0.021) in newly diagnosed Graves' patients.
      CONCLUSION: in this study strong positive correlation was found between free
      thyroxine (fT4) and left ventricular ejection fraction (LVEF) in newly diagnosed
      Graves' patients.

PMID- 18046062
TI  - Does hyperbaric oxygen administration decrease side effect and improve quality of
      life after pelvic radiation?
AB  - AIM: to evaluate the influence of HBOT to the side effect and quality of life
      after pelvic radiation. METHODS: this is an open randomized, parallel,
      prospective study conducted in Department of Obstetrics and Gynecology, Oncology
      Division and Department of Radiotherapy. Endoscopy procedure was performed in
      Department of Internal Medicine and tissue biopsy in Department of Pathology
      Anatomy. The hyperbaric oxygen therapy (HBOT) was done in Dr. Mintohardjo, Navy
      Seal Hospital Jakarta. The side effect was measured using LENT SOMA scale ratio,
      the quality of life used the Karnofsky score. The difference of two mean was
      analyzed using student t test. RESULTS: of 32 patients undergoing HBOT and 33
      patients as control, the ratio of ASE of control group was 44.1+/-28.2%, HBOT
      group was 0.7+/-30.1%; p<0.001; the LSE of control group was 33.6+/-57.6%, HBOT
      group was -19.6+/-69.4%; p=0.008. Quality of life of control group after
      intervention was 4.5+/-10.7%; HBOT group was 19.7+/-9.6%; p <0.001. After 6
      months of intervention the quality of life was 2.5+/-16.1% in the control group,
      and HBOT group was 15.2+/-14.7%; p =0.007. CONCLUSION: the study showed that HBOT
      decreased acute and late side effect, also improved the quality of life of
      patients with proctitis radiation.

PMID- 18046063
TI  - The cut-off point of interleukin-6 level in acute coronary syndrome.
AB  - AIM: this study aimed to observe whether the interleukin-6 level in acute
      coronary syndrome (ACS) patients were higher than those in coronary heart disease
      (CHD) patients. In addition, we would like to observe the cut off point of
      interleukin-6 level in ACS. METHODS: this cross sectional study were conducted at
      Dr. Cipto Mangunkusumo General Hospital (RSUPN-CM), Persahabatan Hospital, MMC
      Hospital and Medistra Hospital, Jakarta. The study started from 1 May 2005 to 5
      May 2006. RESULTS: in this observational study, as many as 62 CHD patients were
      collected and 84 ACS that met the study criteria. Demographic analysis showed
      that there was no difference in ages among the two groups (ACS and CHD). The risk
      factors of dyslipidemia, hypertension and lipid profile in the two groups did not
      differ significantly. Waist circumference and IMT, systolic and diastolic blood
      pressures in the two groups did not also differ significantly. Smoking was more
      prevalent in the groups of ACS than in the groups of CHD. In this study the IL-6
      level in ACS (mean 40.85 pg/mL, SD 41.71, CI 95% 25.63-42.08 was higher than that
      in CHD (mean 4.58 pg/mL, SD 9.61, CI 95% 2.14-7.02). To identify the IL-6 level
      as the predictor for the occurrence of ACS, sensitivity and specificity were
      calculated at various cut-off points of IL-6 level. At cut-off point of IL-6 4.43
      pg/mL the highest sensitivity (89.95%) and highest specificity (77.42%) were
      found with ROC of 0.87. CONCLUSION: it could be concluded that the IL-6 level in
      ACS were higher that those in CHD. The IL-6 level 4,43 pg/mL could differentiate
      the acute condition (ACS) and stable condition (non-ACS) with sensitivity of
      89.95% and specificity of 77.42%, and ROC of 0.87.

PMID- 18046064
TI  - Hepatoid carcinoma of the gallbladder.
AB  - Hepatoid carcinoma is a special type of extrahepatic tumor associated with
      hepatic differentiation, and has the morphological and functional features of
      hepatocellular carcinoma. Hepatoid carcinoma of the gallbladder is very rarely
      reported in the literature. We report a case of hepatoid carcinoma of the
      gallbladder in a 71-year-old female who presented with abdominal pain and was
      first diagnosed as cholelithiasis with cholecystitis. The microscopic findings of
      the gallbladder after cholecystectomy showed an area of tumor with polygonal
      cells, eosinophilic cytoplasm, distinct cell borders, round vesicular nuclei and
      prominent nucleoli, arranged in trabecular pattern resembling hepatocellular
      carcinoma intermingled with areas of adenocarcinoma or cholangiocarcinoma. The
      specimen from the pancreas also showed the same type of tumor cells.
      Histochemically, some of tumor cells were positive for Victoria Blue, Stein, and
      PAS. The immunohistochemistry for alpha-fetoprotein (AFP) showed strong intra
      cytoplasmic positivity, both in tumor cells with hepatic differentiation and
      tumor cells with bile duct epithelium differentiation. Based on these findings,
      this case was diagnosed as hepatoid carcinoma of the gallbladder with metastasis
      to the pancreas. This is the first case that has been reported in our department.

PMID- 18046065
TI  - Colitis amebiasis with symptom of occasional dripped anal bleeding.
AB  - Colitis amebiasis is usually characterized by bloody and mucous diarrhea,
      abdominal pain and anal discomfort. However, there is unusual manifestation of
      colitis amebiasis, such as occasional dripped anal bleeding, which sometimes
      spouted. Therefore, we often do not suspect such symptoms for colitis amebiasis.
      Laboratory examination includes complete laboratory test, coagulation and
      hematologic test, ICT TBC and colonoscopy. The pathology anatomy examination
      reveals positive results of trophozoites. Treatment by using metronidazole tablet
      provides good result for this disease.

PMID- 18046066
TI  - Percutaneous angioplasty in the diabetic foot.

PMID- 18046067
TI  - Diagnosis and treatment of hematochezia: guideline for clinical practice.
AB  - Hematochezia as an acute and chronic lower gastrointestinal bleeding could be
      caused by diverticulosis, angiodysplasia, neoplasm, perianal disorders, Meckel's
      diverticulum, colitis (infectious and non-infectious) intussusception, and many
      others. Lower gastrointestinal bleeding mostly occurs in older age. Mortality
      caused by acute and chronic lower gastrointestinal bleeding is very high. On the
      other hand, there are difficulties in clinical practice to find the cause and
      making the diagnosis and therapy for hematochezia. Fortunately, the progress and
      development in medical technology, especially colonoscopy and arteriography, has
      assisted in clinical practice.

PMID- 18046068
TI  - Prenatal diagnosis of a fetal abdominal eventration: a rare congenital abdominal
      wall defect.
AB  - We report a case of abdominal eventration associated with cystic fibrosis,
      diagnosed by mid-trimester ultrasonography. The defect concerned the abdominal
      muscles and their aponevrotic sheath, but respected the skin. There was no
      associated malformation. The outcome was favorable after surgery, and the infant
      is well at the age of 6 months.

PMID- 18046069
TI  - Selective feticide in monoamniotic twin pregnancies by umbilical cord occlusion
      and transection.
AB  - OBJECTIVES: In monoamniotic twin pregnancies discordant for fetal anomaly,
      parents may opt for selective feticide. However, the normal co-twin remains at
      risk of sudden demise from cord entanglement. We report on three cases of
      successful selective feticide by cord occlusion combined with cord transection.
      METHODS: We describe technical details and outcome of three monoamniotic twin
      pregnancies discordant for fetal anomaly (two cases of anencephaly and one case
      of congenital heart block) in which cord occlusion was followed by transection of
      the cord using contact laser. RESULTS: The fetoscopic cord occlusion and
      transection using laser was successfully performed at 15, 16 and 19 weeks
      gestation, respectively. In one case, amniotic fluid leakage occurred after
      fetoscopy. The surviving co-twins were born at 36, 38 and 36 weeks gestation,
      respectively; two of the three were born vaginally and they were all healthy.
      CONCLUSION: In monoamniotic twins, selective feticide using laser occlusion and
      transection of the umbilical cord is technically feasible and can lead to near
      term vaginal birth of healthy co-twins.

PMID- 18046070
TI  - A retrospective and theoretical evaluation of rapid methods for detecting
      chromosome abnormalities and their implications on genetic counseling based on a
      series of 3868 CVS diagnoses.
AB  - OBJECTIVES: To report our experience over the past 10 years of chorionic villi
      sampling (CVS) prenatal diagnosis in a high-risk population for chromosomal
      anomalies, and to analyze, according to the results, the advantages and
      disadvantages of using quantitative fluorescence polymerase chain reaction (QF
      PCR) in amniotic fluid with respect to a conventional semi-direct cytogenetic CVS
      method in a retrospective theoretical review. METHODS: We performed 3,868
      cytogenetic analyses from CVS using a semi-direct culture method in a selected
      high-risk population for chromosomal abnormalities and we compare our findings
      with the theoretical results obtained using QF-PCR on amniotic fluid. RESULTS:
      The rate of chromosomal anomalies detected with the semi-direct CVS cytogenetic
      study, excluding confined placental mosaicism (CPM), was 6.8%. 26.3% of all them
      would be missed by using QF-PCR only and among them, 21.4% of cases would
      represent a severe adverse obstetric outcome. CONCLUSIONS: We think that semi
      direct CVS cytogenetic analysis in comparison with QF-PCR in amniotic fluid is
      similarly rapid, performed earlier and more complete, allowing the chromosomal
      diagnosis in the first trimester of gestation. We propose the use of QF-PCR as an
      additional method to semi-direct CVS analysis in order to avoid false-negative
      results, as a rapid alternative to long-term culture.

PMID- 18046071
TI  - Fetal goiter and bilateral ovarian cysts.
AB  - A unique case of fetal goiter accompanied by bilateral ovarian cysts in a mother
      treated with methimazole for Graves'disease is reported. The abnormal findings
      were detected by ultrasound at 31 weeks of gestation. Umbilical fetal blood
      sampling revealed elevated serum TSH, normal concentrations of free T 4 , normal
      FSH and LH and high concentrations of E 2 . A series of weekly amniocenteses and
      intra-amniotic injections of levothyroxine was initiated, along with a reduction
      of the mother's methimazole dosage. The level of TSH in amniotic fluid was
      initially high, but was considerably reduced by each injection and followed by a
      gradual reduction of fetal goiter as well as the left ovarian cyst. The right
      cyst ruptured spontaneously. At 36 weeks + 4 days, the patient underwent elective
      caesarean section and gave birth to a female, weighing 2,880 g with 1- and 5-min
      Apgar scores of 10. The thyroid gland appeared normal in size, and cord blood TSH
      and free T 4 were both within normal limits. At ultrasound control 6 days later,
      the right ovarian cyst was not visible, while the left cyst was still present.
      Thus, our report supports previous findings that fetal goiter can be treated
      successfully with intra-amniotic injection of levothyroxine.More importantly, it
      shows that fetal hypothyroidism with elevated levels of TSH can be accompanied by
      ovarian cysts,suggesting interference between thyreotropic and gonadotropic
      hormones.

PMID- 18046072
TI  - Prenatal diagnosis of abnormal course of umbilical vein and absent ductus venosus
      -report of three cases.
AB  - An abnormal course of the umbilical vein is a rare anomaly. Its association with
      the congenital absence of the ductus venosus is common. We found 3 cases of an
      abnormal course of the umbilical vein and an absent ductus venosus. In 2 of these
      cases, the umbilical vein turned down and continued in the internal iliac vein,
      and no ductus venosus was found. One of these pregnancies was terminated. From
      the continued pregnancy a growth-retarded baby was born. At follow-up
      examinations, mild microcephaly, mildly elevated levels of ammonia, delayed
      speech and mild muscular hypotonia were found. In the third case, the umbilical
      vein turned up from the level of umbilical ring and the anterior of the liver
      above the diaphragma and connected directly into the right atrium. Associated
      complex congenital heart malformations - transposition of the great arteries, and
      ventricular septal defect - were diagnosed prenatally. In the umbilical vein from
      the placenta to the umbilical ring, the flow was low velocity continuous; from
      the umbilical ring to the right atrium, the flow was biphasic high velocity (90
      cm/s). Such an elevated blood flow could be a sign of increased cardiac preload.
      The long-term neurological follow-up of babies with prenatally diagnosed venous
      malformations is necessary.

PMID- 18046073
TI  - Nonhemorrhagic primary obstetric shock.
AB  - OBJECTIVE: Clinical evaluation of nonhemorrhagic primary obstetric shock (NHPOS).
      METHODS: In a retrospective clinical study, data on 8 cases of NHPOS were
      analyzed. Data on patient age, parity, week of gestation, comorbidity, possible
      etiologic trigger, course of disease with clinical picture and laboratory
      findings of coagulopathy, and patient outcome including autopsy findings in two
      lethal outcomes were analyzed. RESULTS: These 8 patients were treated in the
      intensive care unit. One patient died during delivery from cardiopulmonary arrest
      in the state of irreversible obstetric shock, verified by massive pulmonary
      thromboembolism at autopsy. Another patient died from stroke and cerebral coma
      caused by trophoblastic cerebrovascular embolism 5 days after artificial
      abortion, showing a clinical picture of shock and cardiopulmonary arrest. In 1
      patient, severe septic shock developed several hours after premature stillbirth
      and abruptio placentae in the 26th week of pregnancy, associated with
      disseminated intravascular coagulopathy. Four patients developed intrapartum
      NHPOS, with a clinical picture of chest pain, dyspnea, tachycardia, hypotension,
      cyanosis, and disseminated intravascular coagulopathy, as demonstrated by
      laboratory findings. Based on clinical picture and laboratory findings, amniotic
      fluid embolism or trophoblastic embolism was suspected. All these patients
      survived. One patient developed NHPOS during the third labor stage after vacuum
      extraction because of a macrosomic child, followed by disseminated intravascular
      coagulopathy and secondary hemorrhage which necessitated B-Lynch procedures and
      total hysterectomy for massive bleeding. Hereditary thrombophilia was detected in
      subsequent patients. CONCLUSIONS: NHPOS can be caused by amniotic fluid embolism,
      trophoblastic embolism or thromboembolism, and sepsis. These conditions may
      frequently prove fatal due to their abrupt and unexpected course, mostly during
      pregnancy, delivery, or immediately thereafter.

PMID- 18046074
TI  - Brain injury of the survivor diagnosed at 18 weeks of gestation after
      intrauterine demise of the co-twin: a case report.
AB  - Brain injury in a surviving fetus following the demise of a monochorionic co-twin
      has only rarely been reported in the first trimester or early second trimester;
      most documented cases were beyond 20 weeks of gestation.

PMID- 18046075
TI  - Platelet-derived microparticles and platelet count in preterm newborns.
AB  - OBJECTIVE: Does formation of platelet-derived microparticles correspond to
      platelet activation? METHODS: The study was performed in 51 preterm newborns, 25
      girls and 26 boys. The control group consisted of 55 term newborns, 25 girls and
      30 boys. Blood samples were collected from the umbilical artery. The percentage
      of platelet-derived microparticles and platelet count were determined using flow
      cytometric analysis based on the CD61-positive antigen. RESULTS: The percentage
      of platelet-derived microparticles was higher in preterm newborns (5.46) in
      comparison to term newborns (4.22, p < 0.01). We found 4.61% of platelet-derived
      microparticles in preterm female newborns and 6.28% in preterm boys (p < 0.0070).
      The platelet count was 256 x 10(3) microl in girls and 238 x 10(3) microl in
      boys. Female healthy term newborns presented higher values of platelet-derived
      microparticles (4.4%) than male newborns (4.07%, p = 0.4725, table 1). The
      platelet count in girls was found to be 308 x 10(3) microl and in boys 270 x
      10(3) microl. CONCLUSIONS: Higher percentage of platelet-derived microparticles
      in preterm newborns may provide a compensatory mechanism for the hemostatic
      system.

PMID- 18046076
TI  - Early intraperitoneal transfusion and adjuvant maternal immunoglobulin therapy in
      the treatment of severe red cell alloimmunization prior to fetal intravascular
      transfusion.
AB  - This descriptive case study documents the treatment of a cohort of 6 women with
      pregnancies complicated by red cell alloimmunization who in previous pregnancies
      had objective evidence of severe fetal anemia prior to 20 weeks of gestation,
      with accompanying high perinatal loss (66% mortality). In the pregnancies
      described, 5 singletons and 1 dichorionic, diamniotic twin pregnancy underwent
      alternate week, serial intraperitoneal transfusions between 16 and 21 weeks,
      until a gestation when classical fetal intravascular transfusions could be
      commenced. In addition, 4 women consented to have additional, adjuvant maternal
      intravenous gammaglobulin (IVIG) therapy (0.8 g/kg per week). At the first fetal
      blood sampling at a median gestational age of 22 weeks (95% CI 21.2-23.4 weeks)
      the median hemoglobin concentration was 10.1 g% (95% CI 7.4-13.4 g%). In only 2
      cases were the fetal hemoglobin levels at fetal blood sampling between -2 SD and 
      5 SD for gestational age; in 1 case this was associated with fetal mortality.
      This cohort indicates that such treatment may prevent severe fetal anemia from
      developing prior to 20 weeks and, in this cohort, indicated an improved survival
      of pregnancies (86% survival (6/7)), as compared to the previous history. The
      only perinatal mortality occurred in a growth-restricted fetus whose mother had a
      chronic opiate addiction. The fetus died prior to 20 weeks. Of the pregnancies
      that progressed beyond 20 weeks and commenced classical fetal intravascular
      transfusions, the survival was 100%.

PMID- 18046077
TI  - Management of pregnancy in adolescence complicated by acute lymphoblastic
      leukemia.
AB  - The management of the common acute lymphoblastic leukemia in pregnancy has been
      controversial. We report a case of a 16-year-old primigravida with acute
      lymphoblastic leukemia, first presented in pregnancy, which was treated with
      aggressive chemotherapy protocols. Full remission of the disease was achieved.
      The neonate was born at 32 weeks following a cesarean section. The woman remains
      in complete remission, continuing maintenance chemotherapy, 18 months following
      diagnosis. The offspring did not show any abnormality in physical examinations or
      laboratory tests and keeps growing normally 18 months after birth.

PMID- 18046078
TI  - Definition of pentalogy of Cantrell. Commentary on Araujo Junior et al: diagnosis
      of pentalogy of Cantrell by three-dimensional ultrasound in third trimester of
      pregancy (Fetal Diagn Ther 2006;21:544-547).

PMID- 18046079
TI  - A comparative evaluation of various methods for microalbuminuria screening.
AB  - BACKGROUND/AIMS: Microalbuminuria is a marker of abnormal vascular response and a
      predictor of cardiovascular morbidity and mortality. We evaluated a new
      quantitative office-based method to assess urinary albumin excretion (UAE) and
      compared it to other established methods. METHODS: Spot urine samples from 165
      patients were analyzed at a single study site using the HemoCue system, Clinitek
      Microalbumin, and Chemstrip Micral test, as well as at a central laboratory,
      where UAE and creatinine levels were measured. The central laboratory UAE values
      were used as reference. We evaluated the validity of the HemoCue results and
      compared them to the respective data for the laboratory albumin-to-creatinine
      ratio (ACR). Additionally, we assessed, diagnostic sensitivity, specificity, and
      positive and negative predictive values of all four methods, as well as the
      reproducibility of the HemoCue measurements. RESULTS: Linear regression analysis
      demonstrated a good correlation for the HemoCue system (y = 0.9978x - 1.0217, R2
      = 0.904) and ACR (y = 0.0815x + 0.3373, R2 = 0.784). Sensitivity and specificity
      for microalbuminuria diagnosis were 92 and 98% for HemoCue, 73 and 96% for ACR,
      100 and 81% for Clinitek Microalbumin, and 70 and 83% for Chemstrip Micral
      dipstick, respectively. The correlation coefficient of duplicate HemoCue
      measurements was r = 0.98 (p < 0.001). CONCLUSIONS: The HemoCue system for
      microalbuminuria detection was as accurate and precise as laboratory ACR
      estimations. Its diagnostic performance was much better than that of widely used
      dipstick methods.

PMID- 18046080
TI  - Slc26a6 (PAT1) deletion downregulates the apical Na+/H+ exchanger in the straight
      segment of the proximal tubule.
AB  - BACKGROUND/AIM: Slc26a6 (PAT1, CFEX) is a major chloride/base exchanger located
      on the apical membrane of the kidney proximal tubule. The purpose of the present
      study was to examine the effect of Slc26a6 deletion on the apical Na+/H+
      exchanger 3 (NHE3) in the straight segment (S3) of the proximal tubule, which is
      the major site for the reabsorption of filtered chloride in the kidney. METHODS:
      The proximal tubule S3 segment was perfused and the intracellular pH and apical
      Na+/H+ exchanger activity and expression were measured. RESULTS: In the proximal
      tubule straight segments that were microperfused in vitro, baseline intracellular
      pH, measured by BCPCF-AM, was 7.10 +/- 0.02 in Slc26a6-/- and 7.33 +/- 0.02 in
      Slc26a6+/+ animals, a significant reduction in Slc26a6 mutant mice (p < 0.00001).
      The activity of the apical Na+/H+ exchanger was 0.49 +/- 0.02 pH units/min in
      Slc26a6+/+ and 0.26 +/- 0.03 pH units/min in Slc26a6-/- animals, a significant
      reduction in Slc26a6-/- mice (p < 0.0001). Formate-induced intracellular
      alkalinization, which is mediated via NHE3, was significantly blunted in Slc26a6
      /- animals, with an alkalinization magnitude of 0.16 pH unit in Slc26a6-/- versus
      0.37 in Slc26a6+/+ animals (p < 0.00001, n = 5 separate animals). Angiotensin II
      stimulation of NHE3 activity was intact in Slc26a6-/- animals. Buffering capacity
      was comparable in Slc26a6+/+ and Slc26a6-/- mice. Immunoblotting and
      immunofluorescent labeling demonstrated comparable NHE3 abundance and
      distribution in kidney proximal tubules of Slc26a6+/+ and Slc26a6-/- mice.
      CONCLUSION: In conclusion, Slc26a6 deletion downregulates the apical Na+/H+
      exchanger activity in the straight segment of the proximal tubule. The absence of
      a significant renal sodium loss in Slc26a6-null mice, despite NHE3 downregulation
      in the in vitro perfused tubules, points to possible activation of signaling
      pathways that can stimulate the apical Na+/H+ exchanger in vivo.

PMID- 18046081
TI  - Vascular calcification and uremia: what do we know?
AB  - In the last decade, the nephrology community has focused its attention on the
      main cause of morbidity and mortality in chronic renal failure patients:
      cardiovascular disease. In addition, recent studies pointed out that vascular
      calcification (VC) is a major cause of cardiovascular disease in the dialysis
      population. Interestingly, the pathogenesis of VC and soft tissue calcification
      in chronic kidney disease (CKD) has been extensively investigated. Nowadays we
      know that VC is associated not only with passive calcium phosphate deposition,
      but also with an active, cell-mediated process. To better understand the
      pathogenesis of VC in CKD, numerous regulatory proteins have been studied,
      because of their ability to inhibit mineral deposition in the vessels. We here
      examine the state of the art of those substances recognized as regulatory key
      factors in preventing VC in uremic conditions, such as fetuin A (alpha2-Heremans
      Schmid glycoprotein), matrix gamma-carboxyglutamic acid protein, pyrophosphate,
      osteoprotegerin and bone morphogenetic protein. We conclude that at present it is
      too early to introduce these novel markers into clinical practice.

PMID- 18046082
TI  - Identification of apolipoprotein E Guangzhou (arginine 150 proline), a new
      variant associated with lipoprotein glomerulopathy.
AB  - BACKGROUND/AIMS: Lipoprotein glomerulopathy (LPG) is a rare disease characterized
      by thrombus-like substances in markedly dilated glomerular capillaries and
      elevated plasma levels of apolipoprotein E (apoE). Previous studies have shown
      that genetic disorders of apoE may contribute to the pathogenesis of LPG, but LPG
      may not be caused by apoE gene mutations in Chinese patients. This study
      investigated the association of a new variant of apoE with LPG in a Chinese
      family. METHODS: The apoE gene in a family with 4 LPG patients was sequenced. The
      polymerase chain reaction product of coding region of apoE exon 4 was cloned into
      pMD 18-T vector and then sequenced. RESULTS: A novel point mutation in exon 4 of
      the apoE gene was identified in all 4 LPG patients and 1 asymptomatic family
      member. Sequence analysis confirmed a nucleotide G to C point mutation in exon 4
      (base 308) of the apoE gene in all patients and the asymptomatic family member.
      This missense mutation denotes amino acid substitution of the proline residue for
      arginine residue at position 150 of apoE. Those patients were all heterozygotes
      with apoE Guangzhou. One of 2 grandsons was a heterozygous carrier of apoE
      Guangzhou, although he did not have proteinuria. CONCLUSION: The results of this
      study suggest that apoE (arginine 150 proline) is a novel apoE variant that
      etiologically related to LPG. This variant (apoE Guangzhou) may cause a marked
      molecular conformational change of the apoE and thus impair its binding ability
      to lipids.

PMID- 18046083
TI  - Chronic kidney disease is associated with angiographic coronary artery disease.
AB  - BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have a dramatically
      increased risk for cardiovascular mortality. Few prior studies have examined the
      independent association of CKD with coronary anatomy. METHODS: We evaluated the
      relationship between CKD and severe coronary artery disease (CAD) in 261 male
      veterans with nuclear perfusion imaging tests suggesting coronary ischemia. We
      used chart review and patient and provider interviews to collect demographics,
      clinical characteristics, and coronary anatomy results. We defined CKD as an
      estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, based on the
      creatinine obtained prior to angiography. We defined significant coronary
      obstruction as at least one 70% or greater stenosis. We used logistic regression
      to determine whether CKD was independently associated with significant coronary
      obstruction. RESULTS: The likelihood of CAD increased monotonically with
      decreasing eGFR, from 51% among patients with eGFR or = 90 ml/min/1.73 m2 to 84%
      in those with eGFR < 30 ml/min/1.73 m2 (p = 0.0046). Patients with CKD were more
      likely than those without CKD to have at least one significant coronary
      obstruction (75.9 vs. 60.7%, p = 0.016). Patients with CKD also had more
      significant CAD, that is, were more likely to have three-vessel and/or left main
      disease than those without CKD (34.9 vs. 16.9%, p = 0.0035). In logistic
      regression analysis, controlling for demographics and comorbidity, CKD continued
      to be independently associated with the presence of significant CAD (p = 0.0071).
      CONCLUSION: CKD patients have a high prevalence of obstructive coronary disease,
      which may contribute to their high cardiovascular mortality.

PMID- 18046084
TI  - Potential options to optimize therapy of gastroesophageal reflux disease with
      proton pump inhibitors.
AB  - Proton pump inhibitors (PPIs) are antisecretory agents that are widely used in
      the short- and long-term management of gastroesophageal reflux disease (GERD) to
      relieve symptoms, heal esophagitis, and prevent complications, such as strictures
      and Barrett's esophagus. The total healthcare costs of GERD are high, especially
      for maintenance treatment. Therefore, the choice of cost-effective therapeutic
      options is an ineluctable challenge for public health authorities, third-party
      payers, and patients. In some European Union countries, a recent trend of public
      health authorities is to promote the choice of less expensive PPIs, regardless of
      their antisecretory potency--this in spite of the evidence that newer PPIs
      provide superior symptom relief and esophageal erosion healing compared to
      earlier drugs. Several large clinical trials have demonstrated the superiority of
      esomeprazole over other PPIs at standard doses for both initial and continuous
      maintenance therapy in patients with moderate/severe erosive esophagitis. The non
      erosive GERD poses a major challenge as this condition appears more frequently to
      be less responsive to PPIs. The use of PPIs with the strongest antisecretory
      properties might reveal to be more adequate and cost-effective, particularly for
      this indication.

PMID- 18046085
TI  - Effects of spironolactone on corneal allograft survival in the rat.
AB  - PURPOSE: Spironolactone has recently been shown to have suppressive effects on
      several immunoactive and proinflammatory cytokines. In this study, we
      investigated the effects of spironolactone on the prevention of corneal allograft
      rejection in a MHC class I/II mismatch rat corneal transplant model. METHODS:
      Grafted animals for corneal survival analysis were assigned to receive either
      spironolactone suspension (orally, 100 mg/kg/day, n = 7), phosphate-buffered
      saline (PBS, orally, same volume as spironolactone, n = 9) or remained untreated
      (n = 16). Additional grafted rats treated with spironolactone (n = 6) or PBS (n =
      8) were sacrificed on day 12 for quantitative RT-PCR analysis for mechanistic
      studies. RESULTS: Mean (+/-SEM) graft survival was significantly prolonged in
      animals receiving spironolactone (14.9 +/- 2.0 days) compared with both PBS
      treated (12.3 +/- 1.2 days, p = 0.007) and untreated controls (13.0 +/- 1.0 days,
      p = 0.01). We found a decrease in corneal neovascularization in spironolactone
      treated rats compared with the PBS-treated group, although the difference was not
      statistically significant. Spironolactone affected both systemic (down-regulation
      of CD25+ cells in spleen) and local immune response (up-regulation of IL-10 in
      cornea). CONCLUSION: We present initial results demonstrating anti-inflammatory
      effects of spironolactone.

PMID- 18046086
TI  - Proteomic analysis of the trabecular meshwork of rats in a steroid-induced ocular
      hypertension model: downregulation of type I collagen C-propeptides.
AB  - PURPOSE: To investigate global protein expression profiles in the trabecular
      meshwork (TM) of normal and glucocorticoid-induced ocular hypertensive rat eyes
      by proteomic analysis, which has not yet been conducted to date. MATERIALS AND
      METHODS: A rat ocular hypertension model was produced by topical application of
      dexamethasone (DEX) for 4 weeks. Age-matched untreated rats served as controls.
      Intraocular pressure (IOP) was monitored by an electronic tonometer. TM protein
      expression profiling and protein identification was carried out by a two
      dimensional fluorescence differential gel electrophoresis (2-D DIGE) system and
      matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry, respectively. RESULTS: In DEX-treated rats, average IOP was
      elevated significantly, as compared with controls. By the DEX treatment, 14 TM
      protein spots were up- or downregulated consistently in 2-D DIGE analyses.
      Proteins exhibiting more than 2-fold statistically significant change were
      identified by MALDI-TOF mass spectrometry. alpha A-Crystallin and beta A(3)
      crystallin were upregulated, while the C-propeptides of type I collagen were
      downregulated. CONCLUSION: Relatively short-term glucocorticoid application
      induced alteration in the expression of a number of proteins, including
      downregulation of type I collagen C-propeptides. This could reflect impaired
      collagen turnover in the TM of glucocorticoid-treated eyes.

PMID- 18046087
TI  - Fish oil supplementation improves left ventricular function in children with
      idiopathic dilated cardiomyopathy.
AB  - Fish oil has a cardioprotective effect in adults with ischemic heart disease. The
      authors examined the effects of fish oil in children with idiopathic dilated
      cardiomyopathy (DCM). Eighteen DCM patients (group I) and 12 healthy children
      (group III) were given fish oil (10 mL/d). Their cardiac findings were compared
      with those of 11 patients with DCM who did not receive fish oil (group II). After
      6.62+/-1.70 months, left ventricular ejection fraction had increased by 8.44%+/
      3.80% (P<.05), in group I; 2.48%+/-3.85% (not statistically significant) in group
      II; and 0.84%+/-2.34% (not statistically significant) in group III. Left
      ventricular internal diastolic diameter (mm) was reduced by 4.36+/-4.86 (P=.001)
      in group I and 1.92+/-5.37 (P=.263) in group II, but increased by 0.22+/-2.54
      (not statistically significant) in group III. The results suggest that fish oil
      leads to accelerated improvement of left ventricular function. The authors
      believe that if these results are confirmed in larger studies, fish oil should be
      added to the standard anticongestive therapy of children with DCM.

PMID- 18046088
TI  - Dynamic analysis of exercise oxygen consumption predicts outcomes in advanced
      heart failure.
AB  - It is unclear whether cardiopulmonary stress testing provides prognostic
      information in patients with very advanced heart failure receiving contemporary
      medical therapy. Analysis of cardiopulmonary treadmill stress data in a group of
      patients with advanced heart failure and severe functional impairment was
      performed (N=102, peak exercise oxygen consumption [VO2] < or =14 mL/kg/min, 47%
      receiving beta-blockers). Dynamic variables (peak - baseline values) better
      predicted outcomes than did single value peak measurements, especially DeltaVO2.
      Multivariate analysis showed that usage of beta-blockers and DeltaVO2 (both
      P<.05) independently and significantly predicted outcomes. Subgroup analysis
      showed that DeltaVO2 was particularly useful in predicting outcomes in patients
      with ischemic cardiomyopathy or who were not receiving beta-blockers. Thus, in
      patients with very advanced heart failure, cardiopulmonary stress testing-derived
      DeltaVO2 provides important prognostic information useful to help predict
      clinical deterioration or death, particularly for patients with ischemic
      cardiomyopathy or who are not receiving beta-blockers.

PMID- 18046089
TI  - Is heart failure more prevalent in patients with peripheral arterial disease? A
      meta-analysis.
AB  - Because risk factors for heart failure (HF) cluster in persons with peripheral
      artery disease (PAD), the authors conducted a meta-analysis to examine the
      prevalence of HF in individuals with PAD. MEDLINE searches were performed to
      review all PAD clinical trials (1966-2003). Expected control population
      prevalence rates for HF were derived from the National Health and Nutrition
      Examination Survey (NHANES) database. In total, 11,304 patients were evaluated.
      The average age of the patients was 67+/-5 years. The prevalence of HF in
      patients with PAD was 7.9% (range, 5.3%-13.9%) compared with an expected
      prevalence of 4.1%(range, 3.7-4.5%). The relative risk for increased HF
      prevalence among those with PAD was 1.9 (range, 1.35-3.10; P<.001). Thirteen
      (range, 7-19) PAD patients needed to be screened to detect 1 case of HF. The
      presence of PAD is associated with a 2-fold increase in the prevalence of HF. The
      use of PAD as a risk marker for underlying HF may enhance the effectiveness of
      screening criteria for HF detection.

PMID- 18046090
TI  - The frequency of angiotensin-converting enzyme genotype and left ventricular
      functions in the obese population.
AB  - The authors investigated the relationship between angiotensin-converting enzyme
      (ACE) genotype and left ventricular functions in an obese population and compared
      their findings with controls. Ninety-six obese patients and 50 controls were
      enrolled. Obesity was subgrouped into mild (body mass index [BMI] 25-29.9
      kg/m(2)), moderate (BMI 30-34.9 kg/m(2)), and significant (BMI > or =35 kg/m(2)).
      Body fat distribution was categorized according to waist-to-hip ratio and waist
      circumference. Left ventricular systolic and diastolic functions were evaluated
      by echocardiography. ACE gene polymorphism was investigated by standard
      polymerase chain reaction, and frequency distributions were calculated for the
      subgroups. Systolic functional indices were found to be increased in mild and
      moderate obesity subgroups. The obese population had increased left ventricular
      diameters. None of the patients had systolic dysfunction, while diastolic
      dysfunction was significantly more common in the obese group; the frequency of
      diastolic dysfunction was proportionally increased with body mass index.
      Diastolic dysfunction was more common in persons with abdominal obesity. ACE DD
      genotype frequency was increased in moderately and significantly obese subgroups
      and also in all obese patients with diastolic dysfunction.

PMID- 18046091
TI  - Assessment of left ventricular dyssynchrony in patients with heart failure and
      normal QRS duration.
AB  - Cardiac resynchronization therapy (CRT) is an important component of heart
      failure therapy in patients with a left ventricular ejection fraction <35%, class
      III or ambulatory class IV symptoms, and a QRS duration >120 ms. The QRS duration
      criterion for patient selection is imperfect. About 30% of patients with an
      increased QRS duration are nonresponders to CRT and many with a normal QRS
      duration with mechanical dyssynchrony respond to CRT. The authors review the
      currently available echocardiographic tools for the assessment of ventricular
      dyssynchrony in patients with heart failure.

PMID- 18046092
TI  - The cholesterol paradox in heart failure.
AB  - Heart failure (HF) is a common and serious condition that is usually due to
      coronary artery disease (CAD). Hypercholesterolemia is a major risk factor for
      CAD but, paradoxically, patients with advanced HF often have low cholesterol,
      which is associated with a poor prognosis. Cholesterol lowering with statins
      reduces morbidity and mortality in patients with CAD who do not have HF and might
      also have improved outcome in patients with HF had they not been excluded from
      the reported trials. The results of large trials such as the Controlled
      Rosuvastatin Multinational Study in Heart Failure (CORONA) and the Gruppo
      Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Insufficienza
      Cardiaca (GISSI-HF) study addressing the effects of rosuvastatin in HF are keenly
      awaited. In addition to cholesterol lowering, statins have other biologic effects
      that might be responsible for some of their favorable effects. This article
      examines this cholesterol paradox and possible mechanisms.

PMID- 18046093
TI  - Performance measures for patients hospitalized with heart failure: are they
      predictive of clinical outcomes?

PMID- 18046094
TI  - G-CSF-based stem cell therapy for the heart--unresolved issues part B: Stem
      cells, engraftment, transdifferentiation, and bioengineering.
AB  - The authors extend their coverage of recent developments in stem cell-based
      therapy for repairing the heart to cover the basic questions of what stem cells
      should be used and how best to favor their survivability within the injured
      heart. The authors focus their attention on those adult stem/progenitor cells
      that have been best investigated in animal studies for repairing the infarcted
      heart and are the focus of completed or ongoing clinical trials. In addition,
      they discuss the promise that resident cardiac stem cells offer and the recent
      identification of specialized architecturally defined niches within the heart to
      nurse their development. Bioengineering approaches employing off-the-shelf
      mesenchymal stem cell patches may soon provide a way to recreate these niches in
      the scarred heart. Conceivably, these patches might also be seeded with
      prescribed mixtures of culturally expanded autologous stem/progenitor cells that
      would lead to new blood vessel and cardiac myocyte formation. The convergence of
      bioengineering and molecular biology on stem cell therapy would seem to make what
      was once unimaginable, cardiac regeneration, a clinical reality in less than one
      generation.

PMID- 18046095
TI  - Apical ballooning syndrome or takotsubo syndrome: a novel cardiac syndrome.

PMID- 18046096
TI  - Blood pressure--the better biomarker: delay in clinical application.

PMID- 18046097
TI  - Identifying which treated hypertensive patients without known coronary artery
      disease should be tested for the presence of myocardial ischemia by perfusion
      imaging.
AB  - Stress dipyridamole technetium-99(m) sestamibi single photon emission computed
      tomographic imaging was used to study myocardial perfusion in 1116 hypertensive
      patients without known coronary artery disease (CAD). The test confirmed the
      presence of CAD in 28.9% of patients. As expected, patients with diabetes
      mellitus (DM) had a significantly higher prevalence of myocardial perfusion
      abnormalities (35.9% vs 23.9%; odds ratio, 1.79; 95% confidence interval [CI],
      1.38-2.33; P<.0001) and high-risk myocardial imaging (16.4% vs 10.6%; odds ratio,
      1.67; 95% CI, 1.18-2.37; P=.004) than those without DM. Odd ratios further
      increased, again as expected, with dyslipidemia (2.19; 95% CI, 1.54-3.12;
      P<.0001), peripheral arterial disease (2.61; 95% CI, 1.77-3.85; P<.0001),
      microalbuminuria (3.03; 95% CI, 1.91-4.82; P<.0001), and abnormal
      electrocardiographic findings (3.06; 1.68; 95% CI, 2.08-4.48; P<.0001). This
      large cohort study showed that more than 1 of 4 treated hypertensive patients
      have subclinical CAD. These study data should be clinically helpful in selecting
      hypertensive patients who are the most suitable candidates to screen for the
      presence of CAD.

PMID- 18046098
TI  - Understanding uncontrolled hypertension: is it the patient or the provider?
AB  - The relative contributions of adherence and treatment intensity to blood pressure
      (BP) control are not well understood. The authors studied patients with
      uncontrolled hypertension (N=410) from 3 primary care clinics in the Veterans
      Affairs (VA) medical system. A questionnaire was used to assess patient adherence
      to therapy, and VA system pharmacy fills were used to assess the intensity of the
      antihypertensive regimen. At baseline, an inadequate antihypertensive regimen was
      implicated as the most probable reason for uncontrolled BP in a majority of
      patients (72%), while nonadherence could only be implicated in 13%. In
      multivariate longitudinal analyses, patients who had an increase in their medical
      treatment during the study had lower final diastolic BP levels compared with the
      patients who did not (-3.70 mm Hg; P<.05). While patient adherence to therapy
      plays a role, vigorous clinical management by the clinician is a more important
      contributor to BP control.

PMID- 18046099
TI  - The relationship between nighttime dipping in blood pressure and cerebral
      hemodynamics in nonstroke patients.
AB  - Inadequate dipping in nighttime blood pressure (BP) is associated with
      cerebrovascular disease. The authors aimed to determine whether inadequate
      nocturnal dipping was associated with abnormalities in cerebrovascular
      hemodynamics in individuals without stroke. Participants in this study underwent
      24-hour ambulatory BP monitoring followed by morning transcranial Doppler
      measurements of blood flow velocities (BFVs) in the middle cerebral artery during
      supine rest, head-up tilt, hypocapnia, and hypercapnia. Nighttime BP decline by
      <10% was considered nondipping. Of the 102 nonstroke participants (mean age, 53.6
      years), 35 (34%) were dippers. Although nondippers had similar BFV and
      cerebrovascular resistance (CVR) while supine, they had a lower BFV (P=.04) and
      greater CVR (P=.02) during head-up tilt compared with dippers. Moreover, greater
      nighttime dipping in both systolic BP (P=.006) and diastolic BP (P=.03) were
      associated with higher daytime BFV and lower CVR (P=.01 for systolic BP; P=.02
      for diastolic BP). Inadequate nocturnal BP dipping is associated with lower
      daytime cerebral blood flow, especially during head-up tilt.

PMID- 18046100
TI  - Why some adult Canadians do not have blood pressure measured.
AB  - Regular blood pressure (BP) measurements are required to identify people with
      hypertension and to optimally manage their cardiovascular risk. Analyses of data
      from the 2000-2001 Canadian Community Health Survey showed that most adult
      Canadians have had a BP assessment in the previous 2 years and few have never had
      one. Large numbers of persons without BP recordings were observed, however, among
      persons who were younger, were male, who did not have either a regular doctor or
      physician contact in the previous year, who were recent immigrants or visible
      minorities (nonwhite and non-Aboriginal), and who spoke neither French nor
      English. Common reasons reported for not having a BP assessment included
      believing it was not necessary and simply not getting around to it. Education
      programs targeting those at risk as well as more convenient BP screening may
      improve awareness and testing.

PMID- 18046101
TI  - 24-hour blood pressure monitoring in the evaluation of supine hypertension and
      orthostatic hypotension.
AB  - The presence of orthostatic hypotension has been shown to be a significant,
      independent predictor of all-cause mortality. Systolic and diastolic orthostatic
      hypotension, reversal of the circadian pattern, and postprandial hypotension are
      some of the hemodynamic factors that may contribute to the increased mortality
      seen in patients with orthostatic hypotension. The high variability of blood
      pressure in orthostatic hypotension cannot usually be adequately assessed by a
      one-time measurement. In this group of patients, 24-hour ambulatory.

PMID- 18046102
TI  - Masked hypertension definition, impact, outcomes: a critical review.
AB  - The phenomenon of masked hypertension (MH) is defined as a clinical condition in
      which a patient's office blood pressure (BP) level is <140/90 mm Hg but
      ambulatory or home BP readings are in the hypertensive range. The prevalence in
      the population is about the same as that of isolated office hypertension; about 1
      in 7 or 8 persons with a normal office BP level may fall into this category. The
      high prevalence of MH would suggest the necessity for measuring out-of-office BP
      in persons with apparently normal or well-controlled office BP. Reactivity to
      daily life stressors and behavioral factors such as smoking, alcohol use,
      contraceptive use in women, and sedentary habits can selectively influence MH. MH
      should be searched for in individuals who are at increased risk for
      cardiovascular complications including patients with kidney disease or diabetes.
      Individuals with MH have been shown to have a greater-than-normal prevalence of
      organ damage, particularly with an increased prevalence of metabolic risk
      factors, left ventricular mass index, carotid intima-media thickness, and
      impaired large artery distensibility compared with patients with a truly normal
      BP level in and out of the clinic or office. Also, outcome studies have suggested
      that MH increases cardiovascular risk, which appears to be close to that of in
      office and out-of-office hypertension. The aim of this review was to define the
      entity of MH, to describe its prevalence in the general population, and to
      discuss its correlation with cardiovascular events.

PMID- 18046103
TI  - Control of blood pressure: does it matter which agent you use?
AB  - A panel was convened to discuss the question, "Is blood pressure lowering the
      sole determinant of outcome, or do specific drugs make a difference?" The panel
      was moderated by Marvin Moser, MD, Clinical Professor of Medicine at the Yale
      University School of Medicine, New Haven, CT. Panelists included Norman Kaplan,
      MD, Clinical Professor of Medicine at the University of Texas Southwestern
      Medical Center at Dallas, TX, and William Cushman, MD, Professor of Medicine at
      the University of Tennessee in Memphis, TN. The discussion was supported by
      Boehringer Ingelheim, and each author received an honorarium from Boehringer
      Ingelheim for time and effort spent participating in the discussion or reviewing
      the transcript for intellectual content before publication. The authors
      maintained full control of the discussion and the resulting content of this
      article.

PMID- 18046104
TI  - Finding vs controlling hypertension--mind the gap!

PMID- 18046105
TI  - New recommendations for blood pressure treatment goals in coronary disease.

PMID- 18046106
TI  - The evolution of combination therapy in treating hypertension.

PMID- 18046107
TI  - Emerging insights in the first-step use of antihypertensive combination therapy.
AB  - The blood pressure (BP) goals set by hypertension management guidelines (<140/90
      mm Hg in uncomplicated hypertension; <130/80 mm Hg in type 2 diabetes or kidney
      disease) are not being achieved in a high proportion of patients, partly because
      monotherapy is insufficient in many patients. In particular, patients with
      uncontrolled moderate or severe hypertension and/or associated cardiovascular
      risk factors remain at high risk for cardiovascular events and hypertensive
      emergency. In recognition of the urgency of treating moderate and severe
      hypertension, the Seventh Report of the Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) advocates the
      initial use of 2-drug therapies in patients with systolic BP levels >20 mm Hg
      above goal or diastolic BP level >10 mm Hg above goal. Regimens should usually
      include a thiazide diuretic and, for patients with diabetes or kidney disease, an
      angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.
      Recently, clinical trial data have shown that first-step antihypertensive
      treatment of moderate and severe hypertension with carefully chosen fixed-dose
      combinations provides a high rate of BP goal achievement, a simplified dosing
      regimen, and superior tolerability compared with monotherapy.

PMID- 18046108
TI  - Initial combination therapy with irbesartan/hydrochlorothiazide for hypertension:
      an analysis of the relationship between baseline blood pressure and the need for
      combination therapy.
AB  - Hypertension treatment guidelines recommend initiating 2-drug therapy whenever
      blood pressure (BP) is > or =20 mm Hg systolic or > or =10 mm Hg diastolic above
      goal. This post hoc pooled analysis of 2 multicenter, randomized, double-blind,
      active-controlled forced-titration studies in 1235 patients with moderate and
      severe hypertension examined how baseline BP levels relate to the need for
      combination therapy by comparing the antihypertensive efficacy and tolerability
      of once-daily fixed-dose irbesartan/hydrochlorothiazide (HCTZ) 300/25 mg compared
      with irbesartan 300-mg or HCTZ 25-mg monotherapies. In study 1, patients with
      severe hypertension (seated diastolic BP [SeDBP] > or =110 mm Hg) were treated
      for 7 weeks with irbesartan or irbesartan/HCTZ combination therapy, with forced
      titration after week 1. In study 2, patients with moderate hypertension (seated
      systolic BP [SeSBP] 160-180 mm Hg or SeDBP 100-110 mm Hg) were treated for 12
      weeks with irbesartan/HCTZ, irbesartan monotherapy, or HCTZ monotherapy, with
      forced-titration after week 2. The relationship between baseline BP and the
      likelihood of achieving BP goals (SeSBP <140 mm Hg or SeDBP <90 mm Hg; SeSBP <130
      mm Hg or SeDBP <80 mm Hg) as well as the antihypertensive response was evaluated
      at week 7/8. The need for combination therapy increased with increasing baseline
      BP and lower BP goals across the range of BP levels studied, with a comparable
      adverse effect profile to monotherapy. These results suggest that the likelihood
      of achieving an early BP goal for a given BP severity should be considered when
      choosing initial combination therapy vs monotherapy.

PMID- 18046109
TI  - The efficacy and safety of initial use of irbesartan/hydrochlorothiazide fixed
      dose combination in hypertensive patients with and without high cardiovascular
      risk.
AB  - A post hoc pooled analysis of 2 multicenter, randomized, double-blind, active
      controlled force-titration studies assessed the antihypertensive efficacy and
      tolerability of 7 to 8 weeks' once-daily fixed-dose
      irbesartan/hydrochlorothiazide (HCTZ) 300/25 mg in 796 stage 1 or 2 hypertensive
      patients according to age (65 years or older or younger than 65) (n=121 or 675)
      and presence or absence of obesity (n=378 or 414), type 2 diabetes (n=99 or 697),
      and high World Health Organization-defined cardiovascular risk (n=593 or 202).
      Systolic/diastolic blood pressure reductions (27-31/16-22 mm Hg) were similar
      regardless of age, obesity, and type 2 diabetes status and were greater in high-
      vs low-risk patients. Dizziness (2.0%-3.7%), hypotension (0%-0.7%), and syncope
      (0%) were rare and not centered in any subgroup. There was no hypotension in the
      elderly or in type 2 diabetics. Irbesartan/HCTZ provided consistent blood
      pressure lowering and tolerability regardless of age, obesity, and type 2
      diabetes and greater efficacy in patients with high cardiovascular risk.

PMID- 18046110
TI  - The ultimate challenge.

PMID- 18046112
TI  - Medical school expansion: deja vu all over again?
AB  - The first two decades of the 21st century may well be viewed by future
      generations as the second great expansion of post-Flexnerian medical education in
      the United States. Given that medical schools are now significantly increasing
      class size for only the second time in 100 years, it is instructive to remember
      the last era -- the 1960s and 1970s -- when these challenges were also forefront
      in the minds of the medical education community.A review of the literature from
      that period indicates that medical educators had similar concerns as today: the
      cost of expansion, national health policy, graduate medical education, community
      based clinical education, interdisciplinary health professions education and care
      delivery, and the management of expansion efforts. Two other issues not fully
      represented in the literature from the 1960s and 1970s are apparent in 2007:
      graduating a diverse cadre of physicians and creating regional four-year branch
      campuses. While many concerns about medical school expansion from 50 years ago
      are with us today, one of the most significant responses from the 1960s and 1970s
      -- a large influx of federal funding -- does not appear on today's horizon. The
      novel strategies that today's generation of medical educators will adopt to
      address projected physician shortages are still emerging.

PMID- 18046113
TI  - Phoenix rises, with Tucson's help: establishing the first four-year allopathic
      program in the nation's fifth largest city.
AB  - The authors describe the expansion of The University of Arizona College of
      Medicine from Tucson, Arizona, into Phoenix. They explain how the new Phoenix
      program, in partnership with Arizona State University, is one college of medicine
      for the state of Arizona, governed by a single accreditation by the Liaison
      Committee for Medical Education (LCME). The authors present 21 lessons to be
      considered early in a medical school expansion process: clearly establish
      responsibility, authority, and accountability; define activities under university
      purview and those that require broader engagement; delineate college-wide versus
      campus-specific functions; clearly define the intent of the new initiative; get
      frequent input from the LCME; use LCME input to ensure a student focus; be
      cautious in using consultants; use respected local "brokers"; create a single
      locus for input and concerns; educate constituencies about medical school
      requirements; engage leadership to create linkages across sites; encourage
      communication between leaders in both sites; discriminate between shared and
      distinctive local curriculum elements; consider the effort and experience
      required to develop a full curriculum versus those required to develop specific
      local curricular areas; create simple, transparent admission processes; define
      faculty profiles for the new program; ensure sufficient resources for core
      faculty; budget based on national metrics; create core mission-based principles
      to frame discussions and decisions; segregate clinical affiliation discussions
      from curriculum and recruitment of basic science faculty; and ensure sufficient
      land. Although these observations are most relevant to institutions planning
      expansions of already accredited programs, they derive from principles and
      practical considerations with wider applicability.

PMID- 18046114
TI  - Preparing for change: the plan, the promise, and the parachute.
AB  - The University of California's (UC's) medical education programs are on the brink
      of change. In January 2007, the UC system completed a multiyear health sciences
      planning effort that is the most comprehensive undertaken in decades. For medical
      student education, the plan calls for an approximately one-third increase in
      enrollment across the system -- from approximately 650 current medical school
      graduates per year to a projected 920 graduates annually by the year 2020. During
      the same period, California's population is expected to increase in size and
      diversity in ways unmatched by any other state in the nation. The plan calls for
      development of new programs that will increase enrollment in unique and
      unprecedented ways. The first phase of this growth is under way and is planned to
      continue through a series of programs that seek to address the needs of
      California's medically underserved communities. Areas of focus include rural
      health and telemedicine (Davis); the Spanish-speaking Latino community (Irvine);
      diverse, disadvantaged communities (Los Angeles); health disparities and health
      equity (San Diego); and the urban underserved (San Francisco and Berkeley). In
      November 2006, UC medical schools received $200 million in bond funding to
      support this growth and to create new telemedicine programs to increase access to
      services provided by faculty physicians. In the coming years, UC medical schools
      will face demographic and budgetary challenges that will require perseverance,
      creativity, and certain leaps of faith. Public expectations are high.

PMID- 18046116
TI  - Addressing health care needs of the Latino community: one medical school's
      approach.
AB  - The Program in Medical Education for the Latino Community (PRIME-LC) at the
      University of California-Irvine (UCI) School of Medicine was designed to improve
      health care delivery, research, and policy in underserved Latino communities.
      Specialized training develops strongly committed physicians with linguistic
      skills and cultural understanding, enabling them to serve Latino patients.
      Presently, the health care system's shortage of providers with this expertise
      renders it unable to address the Latino community's needs adequately. The UCI
      School of Medicine realized they were proposing a radically different type of
      program at the onset of this project -- one designed to address the health care
      needs of a specific ethnic group. Developed with dual goals, PRIME-LC aspires to
      provide the Latino community with culturally sensitive, Spanish-speaking
      physicians who are well aware of medical and social conditions prevalent among
      Latinos, in addition to physicians with a broad understanding of community
      medicine who are well versed in advocacy and able to become leaders within and
      outside the Latino community. PRIME-LC must be placed within the context of
      predicted physician shortages in the United States attributable to the projected
      population increase in general and, more specifically, within the context of a
      growing Latino population nationwide. As medical schools prepare to increase
      their output, programs like PRIME-LC that address society's special needs deserve
      serious consideration.

PMID- 18046118
TI  - Addressing physician shortages in New Mexico through a combined BA/MD program.
AB  - The University of New Mexico School of Medicine and College of Arts and Sciences
      developed its combined BA/MD degree program, which will increase the medical
      school class from 75 students to 100 in the fall of 2010, to address the critical
      issue of physician shortages in underserved New Mexico. The program, which began
      operation at the undergraduate (i.e., college) level in 2006, expands
      opportunities in medical education for New Mexico students, especially those from
      rural and underserved minority communities, and prepares them to practice in
      underserved areas of New Mexico. In the BA/MD program, students will earn a
      bachelor of arts, a medical degree, and a proposed certificate in public health.
      A challenging liberal arts curriculum introduces the principles of public health.
      Students have unique rural medicine and public health preceptorship opportunities
      that begin in the undergraduate years and continue throughout medical school.
      Students work with a community physician mentor in summer service-learning
      projects during the undergraduate years, then they return for required rural
      medicine rotations in the first, third, and fourth years of medical school.
      Simultaneously, the classroom curriculum for these rural medicine experiences
      emphasizes the public health perspective. High priority has been placed on
      supporting students with academic advising and counseling, tutoring, supplemental
      instruction, on-campus housing, and scholarships. The program has received strong
      support from communities, the New Mexico state legislature, the New Mexico
      Medical Society, and the faculties of arts and sciences and the school of
      medicine. Early results on the undergraduate level demonstrate strong interest
      from applicants, retention of participants, and enthusiasm of students and
      faculty alike.

PMID- 18046119
TI  - Strategies for increasing the physician workforce: the Oregon model for
      expansion.
AB  - The physician workforce shortage and inequity of physician distribution
      throughout Oregon require the Oregon Health & Science University (OHSU) School of
      Medicine to graduate more physicians and increase the number committed to
      practice in nonurban areas. The most cost-effective and expedient method to
      accomplish these goals has been to develop community partnerships and regional
      campuses. However, expansion must be strategically developed to maintain
      educational quality and to minimize the impact on available resources. Leveraging
      partnerships with existing health care delivery systems and major state
      universities makes expansion more expedient and economical. In 2001, the OHSU
      School of Medicine began implementing a four-phase plan to increase medical
      student enrollment. Phase 1 (2001-2006) used only capital budget resources to
      increase enrollment incrementally at the school of medicine's Portland site;
      Phase 2 (2006-2007) creates community partnerships to develop regional sites
      using the physical facilities of partners, again avoiding the need for capital
      investment; Phase 3 (2007-2010) builds on the prototype developed in Phase 2 to
      create additional regional educational sites; and Phase 4 (2010-2015) involves a
      feasibility study and subsequent capital campaign for a facility on Portland's
      south waterfront. Establishing regional campuses and matriculating the student
      population best suited for the physician workforce of the future are key elements
      of the OHSU model of expansion, particularly in addressing the state's physician
      distribution inequities.

PMID- 18046120
TI  - Creating an integrated clinical enterprise at the University of Kentucky: the
      emergence of UK HealthCare.
AB  - If the medical system in the United States is to change, as has been recommended,
      academic medical centers must, in fact, lead this change process. To prepare for
      the future, the University of Kentucky decided to move aggressively toward
      developing an integrated clinical enterprise branded as UK HealthCare, where
      leadership of the various components of the academic medical center make
      strategic and financial decisions together to achieve common organizational
      goals. The authors discuss senior leadership's development of the vision for the
      enterprise and the governance structure that was established to engage board
      members and faculty of the institution. They examine the rigorous strategic,
      facilities, financial, and academic planning that ensued, and the early successes
      achieved. The authors introduce some of the lessons learned by the organization
      during the emergence of UK HealthCare and describe the corporate structure and
      senior management team that was established to support the quick and efficient
      implementation of the planning strategies. It was this corporate structure and
      senior management team which has proven to be an effective agent of change and a
      key to the successful development of a truly integrated clinical enterprise.

PMID- 18046121
TI  - Columbia University College of Physicians & Surgeons.

PMID- 18046122
TI  - Aligning academic and clinical missions through an integrated funds-flow
      allocation process.
AB  - Although much has been written about implementing mission-based management tools
      to help facilitate managing the primary academic missions at academic medical
      centers, there is surprisingly little written on standardized methodologies to
      align financial support across the academic and clinical missions. However,
      professional fee reimbursement has not kept pace with costs, and this, combined
      with potential decreases in research funding associated with the reductions in
      National Institutes of Health funding, creates additional financial challenges
      for academic clinical departments that do not share in technical fee
      reimbursement. As an integrated academic health system, the University of
      Pennsylvania School of Medicine and Health System recently took the opportunity
      to broadly restructure funds-flow opportunities, so as to help align the
      strategic goals across all of the clinical department activities.

PMID- 18046123
TI  - Organizational factors associated with high performance in quality and safety in
      academic medical centers.
AB  - PURPOSE: Leaders of academic medical centers (AMCs) are challenged to ensure
      consistent high performance in quality and safety across all clinical services.
      The authors sought to identify organizational factors associated with AMCs that
      stood out from their peers in a composite scoring system for quality and safety
      derived from patient-level data. METHOD: A scoring method using measures of
      safety, mortality, clinical effectiveness, and equity of care was applied to
      discharge abstract data from 79 AMCs for 2003-2004. Six institutions (three top
      and three average performers) were selected for site visits; the performance
      status of the six institutions was withheld from the site visit team. Through
      interviews and document review, the team sought to identify factors that were
      associated with the performance status of the institution. RESULTS: The scoring
      system discriminated performance among the 79 AMCs in a clinically meaningful
      way. For example, the transition of a typical 500-bed hospital from average to
      top levels of performance could result in 150 fewer deaths per year. Abstraction
      of key findings from the interview notes revealed distinctive themes in the top
      versus average performers. Common qualities shared by top performers included a
      shared sense of purpose, a hands-on leadership style, accountability systems for
      quality and safety, a focus on results, and a culture of collaboration.
      CONCLUSIONS: Distinctive leadership behaviors and organizational practices are
      associated with measurable differences in patient-level measures of quality and
      safety.

PMID- 18046124
TI  - Merging two universities: the Medical University of Ohio and the University of
      Toledo.
AB  - On July 1, 2006, the Medical University of Ohio officially merged with the
      University of Toledo and became the third largest public institution of higher
      education in the state of Ohio. The combination of the two neighboring
      institutions occurred through the efforts of a number of individuals who
      recognized the potential advantages of a merger and worked quickly through
      challenges by early engagement of stakeholders in the merger process. The
      advantages of a larger, more diverse institution with increased budget and
      research funding outweighed the challenges of bringing two different cultures
      together. Changing the culture and leadership was necessary to allow the process
      to move forward. In addition, statewide political support was mobilized to carry
      forward the legislative actions that permitted the formation of the new
      institution. The transformation of a free standing medical campus to a part of a
      larger university required a fusion of the existing boards of trustees, a new
      organizational structure and a unified strategic plan, all of which occurred in
      the first 12 months after the merger. The college of medicine of the former
      Medical University of Ohio has been strengthened by the merger process, and the
      new University of Toledo has emerged as a much more diverse and complete
      institution.

PMID- 18046125
TI  - Making students cry (or: how hammering home the point can smash the process to
      pieces).

PMID- 18046126
TI  - Medicine and the arts. Scenes from a Mastectomy [excerpt] by Alicia Ostriker.
      Commentary.

PMID- 18046128
TI  - Gold Foundation essay: Thinking outside the box.

PMID- 18046129
TI  - National efforts to reform residency education in surgery.
AB  - Major changes in surgical practice and myriad external mandates have affected
      residency education in surgery. The traditional surgery residency education and
      training model has come under scrutiny, and calls for major reform of this model
      have been made by a variety of stakeholders. The American Surgical Association
      appointed a Blue Ribbon Committee in 2002 to consider the recent changes in
      surgical practice and surgical education and propose solutions that would ensure
      a well-educated and well-trained surgical workforce for the future. This
      committee included representatives from the American Surgical Association, the
      American College of Surgeons, the American Board of Surgery, and the Residency
      Review Committee for Surgery. The committee made several far-reaching
      recommendations relating to residency education in surgery. After the Blue Ribbon
      Committee completed its task in 2004, representatives from the aforementioned
      four organizations, the Association of Program Directors in Surgery, and the
      Association for Surgical Education created a national consortium called the
      Surgical Council on Resident Education (SCORE). This consortium is pursuing
      efforts to reform residency education in surgery and implement several key
      recommendations of the Blue Ribbon Committee. The principal area of focus of
      SCORE is the development of a national curriculum for surgery residency education
      and training. Other activities of SCORE include the development of a Web site to
      support surgery residency education and pursuit of international collaboration.
      SCORE's efforts will be key to offering surgery residents the best educational
      experiences, preparing residents for future practice, and supporting delivery of
      surgical care of the highest quality. The authors examine the current state of
      residency education in surgery and explore efforts underway to reform this
      educational model.

PMID- 18046130
TI  - Brick by brick.

PMID- 18046131
TI  - Redesigning residency training in internal medicine: the consensus report of the
      Alliance for Academic Internal Medicine Education Redesign Task Force.
AB  - Because of numerous criticisms of the content and structure of residency
      training, redesigning graduate medical education (GME) has become a high priority
      for the internal medicine community. From 2005 to 2007, the leadership of the
      internal medicine community, working under the auspices of the Alliance for
      Academic Internal Medicine Education Redesign Task Force, developed six
      recommendations it will pursue to improve residency education: (1) focus
      education around a "core" of internal medicine, which provides the framework for
      both the structure and content of residents' educational experiences, (2) fully
      adopt competency-based evaluation and advancement, which will enhance training by
      focusing on individual learners' needs, (3) allow for increased, resident
      centered education beyond the internal medicine core, because different types of
      practice require customized knowledge and skills, (4) improve ambulatory training
      by providing patient-centered longitudinal care that addresses the conflict
      between inpatient and outpatient responsibilities, (5) use new faculty models
      that emphasize the creation of a core faculty, and (6) align institutional and
      programmatic resources with the goals of redesign, balancing the clinical mission
      of the institution with the educational goals of residency training. Adoption of
      these recommendations will require significant efforts, including pilot projects,
      faculty development, changes in accreditation requirements, and modifications of
      GME funding systems. Opportunities are ample for individual programs to develop
      creative approaches based on the framework for educational redesign outlined in
      this article, and for these educational and clinical redesign initiatives to work
      hand-in-hand for the benefit of patients, faculty, trainees, and institutions.

PMID- 18046133
TI  - Preparing the personal physician for practice: changing family medicine residency
      training to enable new model practice.
AB  - After two years of intensive study, in 2004 the Future of Family Medicine report
      concluded that the current U.S. health care system is inadequate and
      unsustainable, and called for changes within the specialty of family medicine to
      ensure the future health of the American public. With guidance and encouragement
      from many disciplines and health experts, a set of 10 recommendations was
      established to accomplish a transformative change in how family physicians serve
      their patients and how the essential function of primary care is achieved. From
      these recommendations came a period of innovation and experimentation in the
      training of family physicians, entitled Preparing the Personal Physician for
      Practice (P4). The P4 project is a carefully designed and evaluated initiative
      led by the American Board of Family Medicine and the Association of Family
      Medicine Residency Directors and administered by TransforMED, a practice redesign
      initiative of the American Academy of Family Physicians. Fourteen family medicine
      programs were chosen to participate and will put their innovations into practice
      from 2007 to 2012, during which time regular evaluation will be conducted. The
      purpose of P4 is to learn how to improve the graduate medical education of family
      physicians such that they are prepared to be outstanding personal physicians and
      to work in the new models of practice now emerging. The innovations tested by P4
      residencies are expected to inspire substantial changes in the content,
      structure, and locations of training of family physicians and to guide future
      revisions in accreditation and certification requirements.

PMID- 18046134
TI  - Timing of revenue streams from newly recruited faculty: implications for faculty
      retention.
AB  - PURPOSE: To determine the timing and magnitude of revenues generated by newly
      recruited faculty, to facilitate configuration of recruitment packages
      appropriately matched to expected financial returns. METHOD: The aggregate of all
      positive cash flows to central college of medicine administration -- from
      research, clinical care, tuition, philanthropy, and royalties and patents, from
      all faculty newly recruited to the University of Arizona College of Medicine
      between 1998 and 2004 -- was quantified using the net present value (npv)
      methodology, which incorporates the time value of money. RESULTS: Tenure-track
      faculty and, in particular, those with laboratory research programs, generated
      the highest positive central cash flows. The npv for positive cash flows (npv[+])
      during 6 and 10 years for newly recruited assistant professors with laboratory
      research programs were $118,600 and $255,400, respectively, and, for professors
      with laboratory research programs, $172,600 and $298,000, respectively (associate
      professors were not analyzed because of limited numbers). Faculty whose
      appointments at the University of Arizona College of Medicine exceeded 15 years
      in duration were the most productive in central revenue generation, far in excess
      of their numbers proportionate to the total. CONCLUSIONS: The results emphasize
      the critical importance of faculty retention, because even those newly recruited
      faculty who are most successful in central revenue generation (tenure track with
      laboratory research programs) must be retained for periods well in excess of 10
      years to recoup the initial central investment required for their recruitment.

PMID- 18046137
TI  - Long-term cosmetic outcome after breast implantation.
AB  - All women who underwent breast augmentation at 1 public and 1 private clinic in
      Denmark from 1973 to 1988, and available for follow-up, were invited to
      participate in a clinical study including a self-administered questionnaire,
      medical record abstraction, and a clinical examination. One hundred ninety (52%)
      out of 368 eligible women participated. Mean time with implants in situ was 19
      years (range, 5-35). Sixty-one percent of the women had 1 implantation, 23% had 2
      implantations, 16% had 3 or more implantations. Nineteen women (10%) had no
      implants at the time of examination. A large proportion of the women (62%) had
      clinically significant capsular contracture, and only half of the study women
      were found to have satisfactory overall breast appearance at examination. In
      contrast, the majority of women reported satisfaction with their implant surgery
      (60%). The women tended to grade themselves more positively than the examining
      physicians.

PMID- 18046138
TI  - Function of the pectoralis major muscle after combined skin-sparing mastectomy
      and immediate reconstruction by subpectoral implantation of a prosthesis.
AB  - For immediate subpectoral endoprosthetic breast reconstruction after skin-sparing
      mastectomy, the caudal origin of the major pectoral muscle is detached from the
      ribs and caudal part of the sternum. To date, the effect on the function of the
      major pectoralis muscle of this routine procedure is unknown. Therefore, we
      assessed the influence of the muscle's release on the upper-arm torque-strength
      profiles. Eighteen healthy controls and 10 women who had undergone unilateral
      immediate subpectoral prosthetic breast reconstruction underwent strength profile
      measurement by use of the Biodex System 3 Pro. The observations in the healthy
      controls were used to calculate the difference in torque strength between the
      dominant and nondominant side. This difference was used to correct the actual
      measurements in the operated women. In the controls, the torque strength at the
      dominant side was significantly stronger than that at the nondominant side (mean
      difference, 3.5 Nm, or 9.1%; P = 0.002). After subpectoral breast reconstruction,
      the measured torque strength at the operated side was 5.2 Nm, or 14% less than
      that at the nonoperated side (P = 0.001). After correction for the effect of
      dominance, we observed a significant reduction of 7.6 Nm, or 20.1% of torque
      strength at the operated side (P = 0.000). Because the strength loss is
      substantial, patients ought to be informed about the possible postoperative
      muscular deficit, surgeons should endeavor a minimum amount of pectoral release,
      and alternative procedures should be explored.

PMID- 18046139
TI  - Preoperative Angio-CT preliminary study of the TRAM flap after selective vascular
      delay.
AB  - BACKGROUND: The pedicled TRAM (pTRAM) flap is one of the best options for
      autologous breast reconstruction, but vascular complications reported in the
      standard versions are about 30%. To reduce complication rate, especially in high
      risk patients, surgical delay has been suggested. Individual precise preoperative
      location and evaluation of perforating vessels and of variations of the diameter
      of the deep superior epigastric artery (DSEA) are highly desirable for improving
      surgical strategy. Previous reports using color duplex scanning, although
      generally confirming the validity of the delay maneuver, have showed several
      pitfalls. The aim of this report was to demonstrate the usefulness of
      multidetector computed tomography angiography (MDCTA) for preoperative planning
      in patients undergoing pTRAM flap breast reconstruction after selective vascular
      delay. METHODS: Three patients were considered for breast reconstruction with the
      pTRAM flap. An MDCTA was performed before and after selective delay to locate the
      muscle perforators and to show increase in DSEA diameter. Axial images,
      multiplanar reconstruction, and 3D volume images were analyzed. RESULTS: Accurate
      identification of the main perforators was achieved. Location, course, and
      anatomic variations of DSEA were reported. The average increase in diameter of
      the DSEA was 29.3%. CONCLUSION: Preoperative planning of pTRAM flap with MDCTA
      allows surgeons to visualize and locate the dominant perforators and to select
      the best DSEA. Consequently, the choice between the homolateral or contralateral
      rectus muscle is facilitated. The high sensitivity and specificity and the ease
      of interpreting data have made MDCTA a highly promising diagnostic tool for
      planning a pTRAM flap.

PMID- 18046140
TI  - Donor-site morbidity of the inferior gluteal musculocutaneous flap for breast
      reconstruction in teenagers.
AB  - The purpose of this study is to objectively evaluate donor-site morbidity of the
      inferior gluteal musculocutaneous flap in teenagers. All cases of breast
      reconstruction performed between 1996 and 2005 using an inferior gluteal flap
      were reviewed. Flap size, weight, and pedicle origin were noted. Donor-site
      morbidity was assessed for scarring, contour deformity, muscle function, and
      sensation. The charts of 15 patients were reviewed, and 6 patients were available
      for further investigation. The average flap size and weight were 17 cm x 7 cm and
      430 g, respectively. All patients had a well-concealed scar with minimal buttock
      asymmetry. Sensory assessment showed some degree of hypoesthesia in the territory
      of the posterior femoral cutaneous nerve in all patients. There was no functional
      loss. Donor-site morbidity of the inferior gluteal musculocutaneous flap is
      largely related to posterior thigh hypoesthesia despite preservation of the
      posterior femoral cutaneous nerve.

PMID- 18046141
TI  - Nipple reconstruction using the modified top hat flap with banked costal
      cartilage graft: long-term follow-up in 58 patients.
AB  - The long-term projection of nipple reconstruction is a challenge. Fifty-eight
      consecutive female patients underwent 58 nipple reconstructions with modified top
      hat flap with cartilage graft following breast reconstruction in 54 autologous
      tissues and 4 implants, respectively. The average neonipple size was 11.5 mm
      initially and 8.5 mm at a mean follow-up of 44.9 months (range, 24-65 months),
      with a mean decrease in projection of 26.1%. Thirty-three patients achieved an
      excellent result, 20 patients a good result, 3 patients a fair result, and 2
      patients a poor result, respectively. The complication rate was 12.1% (7 of 58
      cases), and there was no statistically significant difference between the
      immediate and delayed groups; the revision rate was 8.6% (5 of 58 cases). The
      modified top hat flap with banked costal cartilage graft provides a sustainable
      solution to the gradual loss of nipple projection, with few complications.

PMID- 18046142
TI  - Combined use of ultrasonic-assisted liposuction and semicircular periareolar
      incision for the treatment of gynecomastia.
AB  - BACKGROUND: Of the wide range of excisional and liposuction techniques used to
      correct gynecomastia, so far, no single one was suitable for all grades of
      gynecomastia. We introduce ultrasonic-assisted liposuction (UAL) combined with
      conventional liposuction and partial gland resection without skin excision as the
      standard surgical technique for all such grades. PATIENTS AND METHODS: Twenty
      eight men (aged 17 to 80 years) were consecutively treated from March 2004
      through April 2006 for grade Ia (n = 3), Ib (n = 2), IIa (n = 6), IIb (n = 6),
      III (n = 8), or IV (n = 3) gynecomastia. Their characteristics and the outcome of
      surgery were retrospectively assessed. RESULTS: A mean of 848 mL (range, 300 to
      1400 mL) of liquefied breast tissue was aspirated, and 31 g (range, 3 to 180 g)
      of fibroglandular tissue were excised per breast. No immediate or delayed
      adjuvant skin reduction was needed in any of the patients. Moderate postoperative
      ecchymosis was observed in 2 patients, but no complications were encountered in
      this series. The cosmetic outcome was good to excellent in all. CONCLUSIONS: UAL
      in combination with gland resection through a minimal caudal semicircular
      periareolar incision and conventional liposuction effectively corrects all grades
      of gynecomastia. This combination has little morbidity, requires no skin
      excision, and leads to uniformly good esthetic results.

PMID- 18046143
TI  - Midface lifting as an adjunct procedure in ectropion repair.
AB  - PURPOSE: To evaluate the efficacy of ectropion repair with adjunctive midface
      lift. METHODS: Retrospective chart review of patients with cicatricial,
      involutional, or paralytic ectropion with midface descent. Ectropion repair with
      adjunctive supraperiosteal midface lifting was performed on each patient.
      Surgical indications included lower eyelid ectropion, lagophthalmos, and/or
      cosmetic deformity. Outcomes analyzed were recurrence or adequacy of ectropion
      correction, complications, and need for further surgery. Surgical success was
      determined by the need for further surgery. RESULTS: A total of 32 procedures
      performed on 22 patients undergoing ectropion repair with adjunctive
      supraperiosteal midface lift were reviewed. Of the 15 procedures for patients
      with cicatricial ectropion, 80% (12 of 15 procedures) had improvement of lower
      eyelid position, without the need for further surgery; 71.4% of procedures for
      involutional ectropion (10 of 14 procedures) resulted in improvement in lower
      eyelid position, without the need for further surgery. There was improvement in
      ectropion in all patients with paralytic ectropion and no recurrences. A total of
      5 patients had recurrences after ectropion repair with midface lift secondary to
      perioperative complications, a shortage of anterior lamella, or due to a heavy
      midface. CONCLUSIONS: We demonstrated that most patients undergoing midface lift
      in addition to ectropion repair have a favorable result. This is to be expected,
      given the close anatomic relationship between the lower eyelid and the midface. A
      midface lift should be considered in all patients who have both ectropion and
      significant midface descent.

PMID- 18046144
TI  - Invited discussion: midface lifting as an adjunct procedure in lower eyelid
      ectropion repair.

PMID- 18046145
TI  - Augmentation of the nasal dorsum with autogenous costal cartilage using the "edge
      on" technique.
AB  - Carved costal cartilage autografts are commonly used for nasal augmentation in
      saddle nose deformities. One major disadvantage of these carved grafts is
      postoperative warping. To prevent warping of costal cartilages, we used the "edge
      on" technique. The inferior border of the cartilage is rotated 90 degrees to
      become the convex dorsum. No cartilage is trimmed or carved, and hence the
      intrinsic stress forces within the graft are not disturbed. The results in 21
      patients are documented with long-term follow up (mean, 4 years) and showed no
      evidence of warping. Other complications, advantages, and disadvantages of the
      technique are discussed.

PMID- 18046146
TI  - Correction of hemifacial atrophy with autologous fat transplantation.
AB  - BACKGROUND: Autologous fat transplantation has frequently been used by many
      surgeons for facial recontouring in esthetic patients, with good long-term
      results. However, this technique has not been used primarily in treating patients
      with hemifacial atrophy, and its efficacy and long-term outcome remain unknown.
      METHODS: In a 7-year period, 31 patients with hemifacial atrophy were treated
      with autologous fat transplantation in our institution. All patients had been in
      their stable phase of the disease for at least 1 year. Autologous fat grafts were
      harvested from the lower abdomen or thigh with our preferred low-pressure syringe
      technique and then spun at the lower speed. The fat grafts were injected into
      multiple areas in multiple tissue planes and tunnels to the diseased side of the
      face. The same procedure was repeated once or twice as necessary after each
      injection in at least 3 months. All patients were followed up to 5 years, and
      their outcomes were evaluated by the patients, plastic surgeons, and laypersons
      separately. RESULTS: Obviously improved facial contour was evident in most
      patients after autologous fat transplantations. More than 65% of the patients in
      this series were assessed as satisfactory by all 3 groups. Between 10% and 30% of
      the patients were mostly satisfactory. Only less than 7% of the patients were
      unsatisfactory. No complications were seen in either donor sites or recipient
      sites in this series. CONCLUSIONS: Autologous fat transplantation can be a good
      treatment of choice for patients with hemifacial atrophy.

PMID- 18046147
TI  - Invited discussion: correction of hemifacial atrophy with autologous fat
      transplantation.

PMID- 18046148
TI  - The pectoralis major muscle extended island flap for complete obliteration of the
      median sternotomy wound.
AB  - The sequence of adverse events initiated by a sternal wound infection today can
      typically be ameliorated by interposing a vascularized flap. The pectoralis major
      muscle due to its propinquity has universally been the workhorse flap for
      minimizing this dilemma, with our experience over the past 25 years being no
      exception as 123 of 156 patients so inflicted required this donor site in some
      format. However, a rectus abdominis muscle had to be used in combination in 22
      patients, particularly for coverage of the xiphoid region, and this can add
      significant morbidity in an already compromised patient population. This
      conundrum provided the impetus starting in 2003 for the development of a
      pectoralis major muscle extended island flap, whereby skeletonizing its vascular
      pedicle back to near the origin of the thoracoacromial axis, the desired extended
      reach can be obtained. Since that time, 18 pectoralis major muscle extended
      island flaps have been successfully used, with only a single wound complication
      still requiring use of a rectus abdominis muscle flap. This has proven to be a
      reliable option that alone allows complete closure of the median sternotomy wound
      while avoiding the need for combined flaps with preservation of the rectus
      abdominis muscle.

PMID- 18046149
TI  - Outcomes in the management of sternal dehiscence by plastic surgery: a ten-year
      review in one university center.
AB  - PURPOSE: Infection rates following median sternotomy vary between 0.2% and 10%.
      These cases are associated with morbidity and mortality rates between 10% and 25%
      and 5% and 20%, respectively. The purpose of this study was to evaluate patient
      outcomes following plastic surgery correction of sternotomy dehiscence (SD).
      METHODS: All patients operated on for an SD following coronary artery bypass
      graft surgery (CABG), between 1995 and 2005, with 1 or more flaps, were included.
      RESULTS: Eighty cases were identified over a 10-year period. The mean age was 64
      (+/-9.1) years. Two or more procedures were required in 17.5% of patients, and
      the mortality rate within 30 days was 12.5%. Significant variability was revealed
      between the cumulative mortality rates of plastic surgeons, from 0.0% to 50.0%.
      Multiple associations were identified for poor outcome, including chronic renal
      insufficiency and early mortality, and obesity with risk of reintervention.
      CONCLUSION: Although patients who undergo surgical correction of a deep sternal
      infection usually tolerate their intervention well, the mortality within 30 days
      remains high. This study has identified several factors explaining morbidity and
      mortality in this patient population.

PMID- 18046150
TI  - The 180-degree perforator-based propeller flap for soft tissue coverage of the
      distal, lower extremity: a new method to achieve reliable coverage of the distal
      lower extremity with a local, fasciocutaneous perforator flap.
AB  - BACKGROUND: Traumatic and nontraumatic defects of the distal third of the tibia
      are challenging in regard to soft tissue coverage. While local, pedicled
      fasciocutaneous perforator flaps allow adequate coverage, the donor site often
      requires skin grafting. When a local perforator flap is designed as a 180-degree
      propeller flap, an excellent esthetic result and direct closure of the donor site
      can be achieved, with minimal morbidity. METHODS: Eight patients with defects in
      the malleolar region were treated with 180-degree propeller flaps based on
      perforators from the tibial and peroneal vessels. RESULTS: One partial flap loss
      was encountered in an insulin-dependent diabetic. Partial superficial
      epidermolysis was encountered in 2 cases and healed without further
      interventions. No other complications were encountered. All patients returned to
      full ambulation within 8 weeks. CONCLUSION: The 180-degree propeller flap is an
      elegant and versatile method to achieve soft tissue coverage with local tissue in
      defects of the distal tibia. Contrary to other local perforator flaps, this
      specific design facilitates direct closure of the donor site. As only local, thin
      tissue is used, no interference with normal shoe wear occurs. Even in older
      patients, this flap has proven to be a reliable option.

PMID- 18046151
TI  - Nonlinear finite element simulations to elucidate the determinants of perforator
      patency in propeller flaps.
AB  - The propeller-type flap design is increasingly used in reconstructive surgery for
      various regions of the body. To date, determinants of perforator patency when
      subjected to twisting have not been elucidated. We propose a simulation model to
      study parameters affecting perforator patency under such conditions. Nonlinear
      finite element procedure was used to simulate a perforator consisting of an
      artery and a vein with both ends fixed. A rigid body was attached to the top of
      the perforator for applying prescribed angular displacement. The effect of the
      following parameters on the pedicle patency was determined: (1) increasing angle
      of twist, (2) vessel stiffness, (3) vessel length, (4) diameter, (5) intraluminal
      pressure, and (6) the presence or absence of blood flow during twisting.
      Simulation results were reported in effective stress and strain on the twisted
      pedicle. In the context of perforator patency, effective strain, which is a
      measure of vessel deformation or collapse, is the more relevant outcome. The vein
      was more prone to occlusion because of its weaker wall and lower intraluminal
      pressure. Four factors that affected perforator patency were identified: angle of
      twist, intraluminal blood pressure, and perforator diameter and length. There was
      no significant difference whether twisting was performed prior to or after
      restoration of blood flow (P > 0.05). Therefore, to optimize condition for
      maintaining perforator patency, the angle of twist should be kept <180 degrees,
      perioperative blood pressure should be kept stable (avoiding periods of
      hypotension), and the selected perforator should be approximately 1 mm in
      diameter and >30 mm in length. We found that the propeller flap is a feasible
      design. This study defined the determinants of perforator patency and will serve
      as a useful guide when performing such flaps.

PMID- 18046152
TI  - The turbinate flap for oronasal fistula closure.
AB  - Extensive scarring may limit available local tissue for closure of the nasal
      epithelial lining in oronasal fistulae, as frequently seen in cleft patients. A
      pedicled mucoperiosteal flap harvested from the inferior turbinate can be a
      valuable alternative to close such defects. Due to dense vascularity of the
      conchal mucosa, an inferior turbinate flap with an average size of 9.9 cm may be
      harvested. This is illustrated in a case of a large nasovestibular fistula in a
      patient after premaxillary osteoplasty and anatomic studies.

PMID- 18046153
TI  - Congenital sporadic clinodactyly of the index finger.
AB  - Congenital sporadic clinodactyly of the index finger is uncommon and has not been
      specifically investigated in previous reports. In this paper, we report on 10
      cases with this deformity to investigate its clinical features and to document
      the results following a closing wedge osteotomy. The study demonstrated that
      clinodactyly of the index finger is a unique entity. It is unilateral, with male
      predominance. It is commonly associated with brachydactyly but is not associated
      with systemic anomalies or mental retardation. Finally, the study showed that the
      side of angulation of the index finger is consistently to the radial side. The
      closing wedge osteotomy technique obtained a satisfactory correction of the
      angulation in all patients (the mean preoperative angulation was 44 degrees and
      the mean postoperative angulation was 13 degrees). The cosmetic outcome was
      considered acceptable in 9 cases. In the remaining patient, the operated index
      finger appeared too short compared with the other fingers. We now believe that it
      was not appropriate to do a closing wedge osteotomy for all cases of sporadic
      clinodactyly of the index finger, and we have designed a new approach of
      management based on 3 factors: the severity of angulation, the age of the
      patient, and the relative degree of brachydactyly of the index finger compared
      with the adjacent middle finger.

PMID- 18046155
TI  - Comparison of craniofacial measurements of young adult African-American and North
      American white males and females.
AB  - Surgical correction of craniofacial disfigurements depends for its success on
      precise knowledge of the craniofacial norms of the patient's racial/ethnic
      groups. The norms of North American whites should be restricted to patients of
      Caucasian origin and not applied to members of other races. This study therefore
      sought to determine differences in anthropometric measurements of the
      craniofacial complex between African-American and North American white subjects
      of both sexes and of similar age (18-25 years old). The study group consisted of
      healthy young adult African-Americans, 50 males and 50 females. The analysis of
      craniofacial morphology was based on 51 anthropometric measurements: 9 cranial,
      10 facial, 8 orbital, 14 nasal, 4 oral and 6 auricular. The results were compared
      with 51 norms previously established for North American whites in the same age
      group, generally based on 109 males and 200 females, fewer in comparisons of some
      nasal measurements (ac-ac, sbal-sbal, ac-sn, nostril axis). Highly significant
      differences between groups were found in every craniofacial region, especially in
      the orbital and nasal areas, and confirmed the need to establish separate norms
      for African-Americans to guide corrective surgery of the head and face.

PMID- 18046154
TI  - Postoperative radiation protocol for keloids and hypertrophic scars: statistical
      analysis of 370 sites followed for over 18 months.
AB  - BACKGROUND: Before 2002, keloids and intractable hypertrophic scars were treated
      at our facility with postoperative irradiation of 15 Gy (the traditional
      protocol). Analysis of the therapeutic outcomes of patients treated with this
      protocol showed that the recurrence rates of keloids and intractable hypertrophic
      scars in the anterior chest wall, as well as the scapular and suprapubic regions,
      were statistically higher than at other sites, while the recurrence rates in
      earlobes were lower. Thus, we customized doses for various sites. This report
      describes our trial of postoperative radiation therapy. METHODS: Between January
      2002 and September 2004, 109 patients with 121 keloid and intractable
      hypertrophic scar sites were treated with surgical excision following the new
      protocol: electron-beam irradiation at total doses of 10, 15, or 20 Gy, depending
      on the site. The recurrence rates and toxicities were historically followed in
      218 patients with 249 keloid and intractable hypertrophic scar sites treated with
      the old protocol of surgical removal followed by irradiation at 15 Gy (without
      variation by site). The minimal follow-up time was 18 months. Statistical
      analysis was performed using Fisher exact probability test. RESULTS: Total
      recurrence rates were 29.3% before 2002 and 14.0% after 2003. The recurrence rate
      in the anterior chest wall was statistically reduced. Outcomes of earlobe did not
      differ between irradiation with 15 Gy or 10 Gy. CONCLUSIONS: Keloids and
      intractable hypertrophic scars should be treated with dose protocols customized
      by site. Our results suggest that keloid and intractable hypertrophic scar sites
      with a high risk of recurrence should be treated with 20 Gy in 4 fractions over 4
      days and that earlobe should be treated with 10 Gy in 2 fractions over 2 days.

PMID- 18046156
TI  - Treatment with antisense oligonucleotide reduces the expression of type I
      collagen in a human-skin organ-wound model: implications for antifibrotic gene
      therapy.
AB  - Increased collagen expression during wound healing causes scar formation,
      abnormal contracture, low tensile strength, functional impairment, and
      disfigurement. A novel ex vivo wound-injury model demonstrated that AS60, an
      antisense oligonucleotide (ASO) to type I collagen, reduced the mRNA and protein
      expression of type 1 collagen. Following a cutaneous wound injury in a human-skin
      organ culture, AS60 injection resulted in a 36% (P < 0.001) and 30% decrease (P <
      0.001) in type 1 collagen mRNA and protein expression after 7 days. Similarly,
      transfection of cultured human fibroblasts with ASO resulted in a 36% decrease (P
      < 0.001) and a 31% decrease (P < 0.001) in type 1 collagen mRNA and protein
      expression. Immunofluorescence of human skin organ culture treated with ASO
      showed a specific reduction in collagen expression. Using AS60 to reduce collagen
      expression in human skin may have implications for its use as a gene therapy
      agent to reduce the formation of fibrotic scarring.

PMID- 18046157
TI  - The evaluation of bone formation of the whole-tissue periosteum transplantation
      in combination with beta-tricalcium phosphate (TCP).
AB  - We investigated the osteogenic potential of a combination graft of beta
      tricalcium phosphate (TCP) and periosteum in the rat calvarial defect model. The
      combination beta-TCP and periosteum graft was grafted into rat calvarial defects;
      the newly formed bone in the defect was studied histologically and
      radiographically and compared with periosteum grafts and TCP grafts. Ten days
      after combination grafting, the grafted periosteum showed cell proliferation and
      Runx2 immunoreaction; 20 days after grafting, new bone formation was seen around
      the beta-TCP; and 30 days after grafting, new bone developed and actively
      replaced beta-TCP, while radiography showed calcified areas. Total bone formation
      of the combination periosteum and beta-TCP graft was significantly increased
      compared with single grafts of beta-TCP or periosteum (P < 0.01). The combination
      graft of periosteum and beta-TCP showed marked bone formation in rat calvarial
      defects. This result suggests that combination grafts may be effective for
      repairing bone defects.

PMID- 18046158
TI  - Effect of human bone marrow stromal cells and dermal fibroblasts on collagen
      synthesis and epithelization.
AB  - In a previous in vitro study, the authors reported that bone marrow stromal cells
      (BSCs) have better wound-healing activities than fibroblasts. The purpose of this
      study was to evaluate the effect of BSCs and fibroblasts on wound-healing
      activity in vivo. Cultured human BSCs and dermal fibroblasts taken from the same
      patients were tested to compare collagen synthesis and epithelization in a rat
      wound model. No-cell-treated animals were used as controls. The BSC group showed
      the highest collagen level, followed by the fibroblast group, and then the no
      cell group (P < 0.05). In addition, the best epithelization was observed in the
      BSC group. These results demonstrate that BSCs better stimulate wound healing
      than fibroblasts in vivo and in vitro.

PMID- 18046159
TI  - First colored illustration and detailed description of hermaphroditism by a
      Turkish surgeon, Serefeddin Sabuncuoglu, in the 15th century.
AB  - Cerrahiyyetu'l-Haniyye (Imperial Surgery), written by the surgeon Serefeddin
      Sabuncuoglu in the 15 century, is the first illustrated surgical book in Turkish
      Islamic literature containing human figures. Sabuncuoglu had begun a new era by
      demonstrating for the first time the application of many surgical methods on
      human beings, with illustrations in the style of miniatures in his handwritten
      work. This was a first in medical history, and, owing to this property,
      Sabuncuoglu's book was one of the most important original works of that period.
      In this study in which we aim to examine Sabuncuoglu's surgical book, in
      particular with regard to the disease of hermaphroditism, we first demonstrated
      the historical development of the subject through general sources. From sources
      concerning Sabuncuoglu, we gathered information on his life and works. Then,
      examining the information on hermaphroditism in Sabuncuoglu's work, we discussed
      this information in light of our current knowledge.

PMID- 18046160
TI  - On the origin of pedicled skin inversion vaginoplasty: life and work of Dr
      Georges Burou of Casablanca.
AB  - The first reports on gender-confirming surgery had been published in Germany in
      the 1920s, but it took some 30 years before sex reassignment surgery for
      transsexuals became generally known. Initially, such surgery was performed mostly
      in Europe and Casablanca. In 1956, the gynecologist Dr Georges Burou (1910-1987)
      independently developed the anteriorly pedicled penile skin flap inversion
      vaginoplasty in his Clinique du Parc in Casablanca. This technique was to become
      the gold standard of skin-lined vaginoplasty in transsexuals. During his life, he
      was to perform well over 800 vaginoplasties for transsexual patients from all
      over the world, but Burou always kept a low profile to be able to continue this
      controversial part of his work in Morocco. Because his work was pioneering and
      innovative, Georges Burou and his vaginoplasty are given a place in the recorded
      history of plastic surgery.

PMID- 18046161
TI  - The last word.

PMID- 18046163
TI  - Response to McLaughlin/Lipworth.

PMID- 18046164
TI  - A method to reduce citation errors while compiling bibliographies.

PMID- 18046166
TI  - The effect of arthrodesis, implant stiffness, and time on the canine lumbar
      spine.
AB  - STUDY DESIGN: Canine posterior lumbar instrumentation and fusion. OBJECTIVES: To
      study effects of implant rod size and time on the stiffness of related spine
      construct elements. SUMMARY OF BACKGROUND DATA: The ideal stiffness of posterior
      spinal implants to successfully treat clinical instability or deformity with
      minimal side effects is unknown. METHODS: Twenty-six canines were divided into 7
      groups: control, and 6 or 12-month survival after sham or lumbar L3-5 arthrodesis
      (facet, posterior, and posterolateral) with either 4.76 or 6.35 mm diameter rod
      pedicle screw instrumentation. Axial flexion-compression stiffness of the L3-5
      segment components and axial compression stiffness of the bypassed and adjacent
      anterior column elements were measured. RESULTS: Posterior instrumentation
      initially increased flexion-compression stiffness of the L3-5 segment more than
      the intrinsic stiffness of the implant due to control of spinal column flexion
      buckling. Sham operation did likewise, apparently by posterior scar tissue
      tethering. The percent contribution of the implant construct to instrumented
      segment stiffness was significantly less at 6 months without further change from
      6 to 12 months; 14% and 22% for 4.76 and 6.35 mm rod constructs, respectively.
      Spinal column as well as posterior column stiffness after fusion was independent
      of rod size at 6 months and increased at 12 months in only the 4.76 mm rod group.
      Bypassed L4 vertebral body stiffness decreased significantly at 6 months, was not
      rod size dependent and changed little between 6 and 12 months. Bypassed disk
      stiffness responded in a biphasic manner, apparently increasing at 6 months with
      significant decrease from 6 to 12 months. Adjacent disk compression stiffness
      progressively decreased over time independent of rod size, also decreasing after
      sham operation. CONCLUSIONS: Both rod sizes were associated with 100% fusion and
      produced similar changes in bypassed bone and disks, and adjacent disks. There
      was delayed fusion stress shielding by 6.35 mm rod constructs.

PMID- 18046167
TI  - Nonoperative treatment of symptomatic spondylolysis.
AB  - SUMMARY OF BACKGROUND DATA: Symptomatic spondylolysis resulting from a stress
      fracture of the pars interarticularis is a cause of low back pain in the juvenile
      and adolescent patient. Treatment is conservative in the majority of cases.
      OBJECTIVE: To analyze the outcome of patients with symptomatic isthmic
      spondylolysis treated nonoperatively with a custom fit thoracolumbar orthosis and
      activity cessation for 3 months followed by an organized physical therapy
      program. STUDY DESIGN: Retrospective case series. PATIENT SAMPLE: Four hundred
      thirty-six juvenile and adolescent patients with spondylolysis. OUTCOME MEASURES:
      Pain improvement, hamstring flexibility, range of motion, resolution of back
      spasms, and return to previous activities. METHODS: Retrospective review of 436
      juvenile and adolescent patients with symptomatic spondylolysis confirmed by
      single-photon emission computed tomography or computed tomography. Clinical
      outcomes were assessed through patient history and physical examination. RESULTS:
      Ninety-five percent of patients achieved excellent results according to a
      modified Odom's Criteria. The remaining 5% of patients achieved good results as
      they required occasional nonsteroidal anti-inflammatory drugs to relieve pain.
      Back spasms were resolved and hamstring tightness and range of motion returned to
      normal in all patients. All patients returned to their preinjury activity level.
      No patients went on to surgery. CONCLUSIONS: Symptomatic juvenile and adolescent
      patients with an isthmus spondylolysis may be effectively managed with a custom
      fit thoracolumbar orthosis brace and activity cessation for approximately 3
      months followed by an organized physical therapy program.

PMID- 18046168
TI  - Anterior corpectomy with iliac bone fusion or discectomy with interbody titanium
      cage fusion for multilevel cervical degenerated disc disease.
AB  - STUDY DESIGN: Clinical and radiologic study evaluating the outcome after anterior
      corpectomy with iliac bone fusion compared with discectomy with interbody
      titanium cage fusion for multilevel cervical degenerated disc disease.
      OBJECTIVES: To investigate the safety and effectiveness of interbody titanium
      cage with plate fixation in multilevel postdiscectomy fusion. SUMMARY OF
      BACKGROUND DATA: The operation for segmental multilevel cervical degenerated disc
      disease remains controversial. Data on safety and efficacy of titanium cages in
      multilevel postdiscectomy fusion are rarely available. We investigated the safety
      and effectiveness of interbody fusion cages with plate fixation and compared the
      clinical and radiographical results between anterior corpectomy and iliac bone
      fusion with plate fixation and multilevel discectomy and cage fusion with plate
      fixation. METHODS: Sixty-two patients were treated with either a multilevel
      discectomy and cage fusion with plate fixation (27 patients, group A) or an
      anterior corpectomy and iliac graft fusion with plate fixation (35 patients,
      group B). We evaluated the patients for cervical lordosis, fusion status, and
      stability 24 months postoperatively on the basis of spine radiographs. The
      patients' neurologic outcomes were assessed by the Japanese Orthopedic
      Association (JOA) scores. Neck pain was graded using a 10-point visual analog
      scale. RESULTS: Both groups A and B demonstrated a significant increase in the
      JOA scores (preoperatively 11.1+/-2.1 and 10.4+/-3.5, postoperatively 14.3+/-2.4
      and 13.9+/-2.1, respectively) and a significant decrease in the visual analog
      pain scores (preoperatively 8.5+/-1.1 and 8.7+/-1.5, postoperatively 2.9+/-1.8
      and 3.0+/-2.0, respectively). However, there was no significant difference
      between groups A and B. Both groups A and B showed a significant increase in the
      cervical lordosis after operation and reached satisfactory fusion rates (96.3%
      and 91.4%, respectively). Three patients (two 2-level corpectomies and one 3
      level corpectomy) had construct failures that required a second operation. Eight
      of 35 patients who underwent iliac bone fusion had donor site pain. The hospital
      stay in group A was significantly shorter than that in group B (P=0.022).
      CONCLUSIONS: Either a multilevel discectomy and cage fusion with plating or a
      corpectomy and iliac bone fusion with plating provides good clinical results and
      similar fusion rates for cervical degenerative disc disease. However, absence of
      donor site complications and construct failures and shorter hospital stay make
      the multilevel discectomy and cage fusion with plate fixation better than
      corpectomy and strut graft fusion with plate fixation.

PMID- 18046169
TI  - Cervical range of motion and alignment after laminoplasty preserving or
      reattaching the semispinalis cervicis inserted into axis.
AB  - STUDY DESIGN: A radiographic study in 111 patients using radiographs was
      conducted. OBJECTIVE: To clarify whether the modified laminoplasty with C3
      laminectomy preserving the semispinalis cervicis (SSC) inserted into C2 could
      maintain the postopertive range of motion (ROM) and sagittal alignment compared
      with conventional C3-C7 laminoplasty reattaching the muscle to C2. SUMMARY OF
      BACKGROUND DATA: Intraoperative injury of the SSC is relevant to the significant
      loss of ROM and the malalignment after laminoplasty. To expose the C3 lamina,
      however, the SSC inserted into C2 could not be preserved in conventional C3-C7
      laminoplasty. METHODS: The ROM and sagittal alignment of 70 patients (group A)
      (52 men, 18 women, mean age 59 y, mean follow-up period 1 y and 7 mo) with C4-C7
      laminoplasty with C3 laminectomy were compared with those of 41 patients (group
      B) (28 men, 13 women, mean age 59 y, mean follow-up period 2 y and 6 mo) with C3
      C7 laminoplasty using radiographs of the cervical spine. RESULTS: Regarding C2-C7
      ROM, the postoperative ROM was larger (P=0.003) and the decrease rate of ROM was
      smaller (P=0.0006), and decreased ROM in extension was smaller (P<0.0001) in
      group A. Regarding O-C2 ROM, the increased ROM was smaller (P=0.043) and
      increased ROM in extension was smaller (P=0.001) in group A. Regarding O-C7 ROM,
      the postoperative ROM was larger (P=0.029) in group A. Regarding the cervical
      alignment, the increased lordotic angle at O-C2 was smaller (P=0.046) in group A.
      CONCLUSIONS: This modified laminoplasty preserving the SSC inserted into C2 is an
      effective procedure for maintaining postoperative ROM, especially in extension,
      and sagittal alignment of the upper cervical spine well.

PMID- 18046170
TI  - Airway changes after anterior cervical discectomy and fusion.
AB  - INTRODUCTION: Anterior cervical discectomy and fusion (ACDF) is a common
      procedure for radicular and spondylotic disease of the cervical spine.
      Radiographs are routinely used to evaluate complications in the postoperative
      ACDF patient, especially airway compromise. Our purpose was to establish baseline
      data on the amount of change that can be expected in the prevertebral soft
      tissues after this procedure in the uncomplicated asymptomatic (no airway
      compromise) 1 or 2-level ACDF patient. Our hypothesis was that the upper cervical
      spinal levels (C2-C4) would experience greater degrees of swelling than the lower
      cervical spine (C5-C7). To date no published data exist in the English literature
      upon which to judge symptomatic patients (experiencing postoperative airway
      distress) radiographically. METHODS: We prospectively evaluated preoperative and
      postoperative x-rays of 32 patients undergoing ACDF for radicular or spondylotic
      cervical pathology. Measurements were taken from the anterior body of the
      cervical spine to the posterior aspect of the airway. The postoperative
      differences for each level from C2 to T1 were calculated. RESULTS: We found that
      the greatest level of swelling or change in the prevertebral soft tissues
      occurred at the mid-body of C4 in uncomplicated cases with an average change of
      10.7 mm. No patients measured greater than 25 mm at C4. CONCLUSIONS: As we
      predicted, the greatest edema was noted in the upper cervical spine. Studies need
      to be performed to compare the radiographic data of symptomatic patients with the
      baseline data we have collected.

PMID- 18046171
TI  - Venovertebral vein: morphometric analysis and significance for the transabdominal
      spine surgeon.
AB  - STUDY DESIGN: Prospective intraoperative findings review. OBJECTIVES: To describe
      the surgical anatomy of the innominate vessel, venovertebral vein, and consider
      its significance for transabdominal surgery. BACKGROUND DATA: It has not
      described in any anatomy textbook or reported papers. MATERIALS AND METHODS: In
      50 patients who underwent anterior lumbar interbody fusion or total disc
      replacement, we found venovertebral vein in 37 patients (74%). The connection
      between venovertebral vein and the left common iliac vein was studied to
      determine where the venovertebral vein drained, and its relationship to the
      iliolumbar vein and middle sacral vein. All parameters were measured with vernier
      caliper and divider. RESULTS: All of the veins studied drained into the posterior
      margin of the left common iliac vein from the L5 vertebral body and were located
      between the iliolumbar vein and the middle sacral vein. The diagonal-vertical
      direction to the vertebral endplate was 64.8% (n=24). The mean diameter of
      venovertebral veins was 2.24+/-0.74 mm (range 1.0 to 3.8 mm). The mean length was
      12.71+/-5.71 mm (range 5.45 to 35.10 mm). The distance from the L5 vertebral
      upper endplate to its origin ranged from 6.05 to 21.25 mm, with a mean of 12.51+/
      3.36 mm. The distance of the 37 venovertebral veins studied from the middle
      sacral vein ranged from 0 to 10.6 mm, with a mean of 5.75+/-2.90 mm. The distance
      from the iliolumbar vein ranged from 14 to 38 mm, with a mean of 22.65+/-5.44 mm.
      The venovertebral vein was found to be closer to the middle sacral vein than to
      the iliolumbar vein statistically (P<0.05). CONCLUSIONS: The surgeon performing
      transabdominal spine surgery especially at the L4-5 level must remain alert to
      the existence of this innominate vein.

PMID- 18046172
TI  - The Ponte procedure: posterior only treatment of Scheuermann's kyphosis using
      segmental posterior shortening and pedicle screw instrumentation.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To examine a consecutive series of
      surgically treated Scheuermann kyphosis that had a posterior only procedure with
      segmental pedicle screw fixation and segmental Ponte osteotomies. SUMMARY OF
      BACKGROUND DATA: The gold standard for surgical treatment of Scheuermann kyphosis
      (a rigid kyphosis associated with wedged vertebral bodies occurring in late
      childhood or adolescence) has been combined anterior and posterior approach
      surgery. Alberto Ponte has advocated a posterior-only procedure with posterior
      column shortening via segmental osteotomies, but his procedure has not been
      widely accepted owing to concerns that without anterior column support there
      would be a risk of correction loss and/or instrumentation failure. With the
      advent of improved spinal instrumentation and fixation with thoracic pedicle
      screws, the Ponte procedure may offer an advantage over anterior/posterior
      reconstruction. METHODS: The study prospectively enrolled 17 consecutive patients
      with Scheuermann kyphosis who were treated with the Ponte procedure by the senior
      surgeon at one institution. Standardized radiographic analysis was performed and
      included full-length coronal and sagittal radiographs preoperatively,
      postoperatively, and at final follow-up. Analysis also included the correction
      obtained through the most severe, wedged segments of the deformity by the
      osteotomies. RESULTS: Seventeen patients had the Ponte procedure satisfactorily
      performed. No patient needed an anterior approach to achieve sufficient
      correction or fusion. There were no reoperations for nonunion or instrumentation
      failure. Correction of the instrumented levels was 61% and of worst Cobb was mean
      49%. The apex of the deformity was measured over the most deformed 3 to 7 wedged
      segments. The average correction across the apex was 9.3 degrees per osteotomy
      (range 5.9 to 15). No patient lost more than 4 degrees of correction through
      their instrumented and fused levels. There were no neurologic complications.
      There was one late infection with a solid fusion treated with instrumentation
      removal and intravenous antibiotics. CONCLUSIONS: Using thoracic pedicle screw
      instrumentation as the primary anchor, the Ponte procedure was successfully
      performed in 17 consecutive patients for Scheuermann kyphosis with no exclusions
      for the size or rigidity of the kyphosis. Results were as good as
      anterior/posterior historical controls with excellent correction and minimal loss
      of correction at final follow-up. This procedure avoids the morbidity and
      extended operative time attributed to the anterior approach. LEVEL OF EVIDENCE:
      Therapeutic study, level IV [case series (no, or historical, control group)].

PMID- 18046173
TI  - The use of fuzzy logic to select which curves need to be instrumented and fused
      in adolescent idiopathic scoliosis: a feasibility study.
AB  - Selection of the appropriate curve fusion levels for surgery in adolescent
      idiopathic scoliosis (AIS) is a complex and difficult task. Despite numerous
      publications on this subject, the decision as to which spinal curve, that is
      proximal thoracic, main thoracic or lumbar, needs to be instrumented and included
      in the fusion relies mostly on each surgeon's past experience, although recently
      published data have revealed a high variability of spinal instrumentation
      configurations among spinal surgeons in AIS. This situation exists because of
      ambiguity and vagueness in the decision process. Our objective is to capture the
      proposed rules for the selection of fusion levels and integrate them in a fuzzy
      logic model to decrease haziness and imprecision in the selection process. Two
      models have been developed, one for proximal thoracic curves and the other for
      lumbar curves. These models were constructed using data from a literature review,
      which allowed the extraction of currently proposed rules and their modeling as
      inputs in a computer software based on fuzzy logic modeling. Five and four inputs
      have been respectively chosen for the proximal thoracic and lumbar model. When
      all input values are entered in the model for a specific subject with AIS, the
      software calculates the level of suggestion for the indication to perform an
      instrumentation and fusion of the high thoracic and/or lumbar curves for this
      particular subject. The usefulness of this approach is demonstrated using
      illustrative cases. This is the first report on the use of fuzzy logic to assist
      the decision-making process in the field of spinal deformity surgery and the
      results suggest that this approach may be useful to facilitate surgical planning
      in difficult or borderline cases of AIS.

PMID- 18046174
TI  - Biomechanical evaluation of an injectable radiopaque polypropylene fumarate
      cement for kyphoplasty in a cadaveric osteoporotic vertebral compression fracture
      model.
AB  - Vertebral compression fractures cause pain, deformity, and disability.
      Polypropylene fumarate (PPF) has shown promise as an injectable cement for bone
      defects but little is known about its performance for kyphoplasty. The purpose of
      this study was to evaluate the biomechanical performance of PPF for kyphoplasty
      in simulated anterior compression fractures in cadaveric vertebral bodies. Thirty
      one vertebral bodies (T9 to L4) from osteoporotic cadaveric spines were
      disarticulated, stripped of soft tissue and compressed on a materials testing
      machine to determine pretreatment strength and stiffness. All fractures were
      repaired with inflatable balloon tamps and either polymethylmethacrylate or PPF
      30 (containing 30% barium sulfate by dry weight) cement and then retested.
      Strength restoration with PMMA and PPF-30 were 120% and 104%, respectively, of
      the pretreatment strengths. For stiffness, PMMA and PPF-30 restored vertebral
      bodies to 69% and 53%, respectively, of the initial values. There was no
      significant difference in treatment with either PMMA or PPF-30. The biopolymer
      PPF-30 exhibits mechanical properties similar to PMMA in a cadaveric kyphoplasty
      model. PPF biopolymer may be a suitable alternative for kyphoplasty.

PMID- 18046175
TI  - Vascularized pedicled rib graft: a technique for posterior placement in spinal
      reconstruction.
AB  - The purpose of this paper is to provide a detailed description of the method to
      harvest a vascularized pedicled rib graft, transpose it to the posterior spine,
      and to straighten it to facilitate posterior spine fusion in patients undergoing
      complex spinal reconstruction.

PMID- 18046176
TI  - Iso-C3D fluoroscopy-based navigation in direct pedicle screw fixation of Hangman
      fracture: a case report.
AB  - Direct pedicle screw fixation of the C2 is rarely performed in trauma owing to
      the risk of damage to the neurovascular structures. Computed tomography-based
      navigation has the problem of change in intersegmental anatomy after positioning
      for surgery. Iso-C-based computer navigation acquires the intraoperative real
      time images after patient positioning and thus avoids registration errors and
      improves accuracy. A Hangman fracture treated by posterior direct pedicle screw
      fixation using Iso-C computer navigation guidance is reported. Postoperative
      computed tomographic images confirmed the accurate placement of pedicular screws.
      Intraoperative fluoroscopy-based computer navigation is advantageous especially
      in an unstable upper cervical spine injury where the likelihood of change in the
      intersegmental relationship is maximal before and after positioning for surgery.
      The Iso-C navigation has the advantages of clarity and accuracy, making safe
      pedicle fixation of C1 and C2 possible despite fractured posterior elements. To
      our knowledge, this is the first reported case of displaced Hangman fracture
      treated successfully using Iso-C fluoroscopic navigation assisted direct pedicle
      screw osteosynthesis in the literature. Intraoperative acquisition of
      fluoroscopic images avoids registration-related problems. Three-dimensional
      fluoroscopic navigation gives excellent accuracy and safety in screw
      instrumentation of Hangman fracture.

PMID- 18046179
TI  - Delayed union of a scapular fracture-an unusual cause of persistent shoulder
      pain.
AB  - INTRODUCTION: Scapular fractures in athletes are rare, although they have been
      reported in football and baseball players. Most scapular fractures heal with
      nonoperative management; delayed union is rarely a problem. CASE SUMMARY: A 15-yr
      old male fell onto his posterior shoulder after he had been pushed into the
      boards and then fell to the ice during a hockey check. He was diagnosed with a
      rotator cuff injury at an outside facility. Initial radiographs were negative.
      The patient was not immobilized, and he continued to play hockey despite
      intermittent pain. Seven months later, he presented to our sports medicine
      clinic, complaining of an aching pain at the base of his left shoulder.
      Examination revealed point tenderness along the base of the scapula, restriction
      of shoulder abduction, rhomboid weakness, scapular winging, and anterior
      impingement-type shoulder pain. A new radiograph, obtained at our sports medicine
      clinic, was nondiagnostic. Magnetic resonance imaging revealed increased signal
      on T2, with bone edema at the lateral margin of the scapular neck. A computed
      tomography scan revealed an unhealed, left-transverse, subglenoid scapular
      fracture. The fracture was nondisplaced. The patient was treated with
      transcutaneous electrical stimulation for 6 months and a physical therapy regimen
      focusing on periscapular strengthening. A final computed tomography scan, 6
      months after initial presentation to our clinic, revealed healing of the
      fracture. Examination was normal. The patient was asymptomatic and was able to
      fully return to sports without any complications. CONCLUSIONS: Although scapular
      fractures in athletes are rare, they may occur, particularly in "contact sports"
      that share the energies of injury seen in high-speed motor vehicle collisions.
      Early identification and proper management are integral to decrease symptoms and
      to avoid protracted disability, particularly in athletes.

PMID- 18046180
TI  - Exercise-induced cardiac troponin T release: a meta-analysis.
AB  - PURPOSE: Cardiac troponin T (cTnT) is a highly specific marker of myocardial
      damage and used clinically in the diagnosis of acute myocardial infarction (AMI).
      Release of cTnT has been demonstrated in several small studies after endurance
      exercise. The purpose of this study was to explore, using a meta-analytic
      approach, the incidence of postexercise cTnT release after endurance exercise.
      METHODS: Articles identified via Pubmed, SportDiscus, and Embase (1997-2006)
      searches using the key words cardiac troponin T, cTnT, cardiac biomarkers, and
      exercise; a search of bibliographies; and consultation with experts in the field
      were entered into a random-effects meta-analysis. We identified 26 relevant
      studies (1120 cases). Age, gender, and body mass of participants, as well as
      exercise mode and duration, were explored as possible moderator variables with
      meta-regressions. RESULTS: Postexercise cTnT levels exceeded the assay detection
      limit in 47% of participants (95% CI = 39-56%). The detection of postexercise
      cTnT after cycling events was approximately half that of running events (27 vs
      52%, P = 0.042). The detection of postexercise cTnT decreased slightly as event
      duration increased (P = 0.022) and mean body mass decreased (P = 0.0033).
      Postexercise detection of cTnT was not affected by age (P= 0.309) and was only
      slightly higher for studies with more males in the sample (P = 0.028).
      CONCLUSIONS: Exercise-induced cTnT release is apparent in almost half of the
      endurance athletes who have been studied to date. Relatively heavy individuals
      competing in shorter endurance events, primarily running marathons, are slightly
      more likely to demonstrate elevated cTnT postexercise than other athletes. These
      data are useful for clinicians evaluating athletes with cTnT elevations after
      competitive endurance exercise events.

PMID- 18046181
TI  - Fitness, fatness, and cardiovascular risk factors in type 2 diabetes: look ahead
      study.
AB  - PURPOSE: Most studies comparing the effects of fitness and fatness on
      cardiovascular (CVD) risk have been done with young, healthy participants with
      low rates of obesity and high levels of fitness. The present study examined the
      association of cardiorespiratory fitness and obesity with CVD risk factors in an
      ethnically diverse sample of overweight/obese individuals with type 2 diabetes.
      METHOD: Baseline data from Look AHEAD, a study of 5145 overweight or obese
      individuals with type 2 diabetes, were used to examine the association of BMI
      categories (overweight, class I, II, or III obesity) and cardiorespiratory
      fitness (assessed with a maximal graded exercise test and categorized by age- and
      gender-specific quintiles) on cardiovascular risk factors and on the odds of
      having hypertension, hyperlipidemia, or HbA1c > or = 7%. RESULTS: BMI categories
      and fitness quintiles were highly associated with each other (P < 0.0001), with
      the heaviest participants being the least fit. Only 2-3% of participants had
      class III obesity and were in the two fittest quintiles or, conversely, were
      overweight and in the two least-fit quintiles. When fitness and BMI were included
      in the same model (adjusting for age, smoking, diabetes duration, and race),
      HbA1c, ankle/brachial index (ABI), and Framingham risk score were most strongly
      associated with fitness. Systolic blood pressure was most strongly associated
      with BMI category. Similar results occurred when waist circumference and fitness
      were considered together. CONCLUSION: In this large, ethnically diverse sample of
      overweight/obese individuals with type 2 diabetes, fitness and fatness were
      highly related to each other but seemed to have different impact on specific CVD
      risk factors.

PMID- 18046182
TI  - Exercise-induced bronchoconstriction in athletes-should we screen?
AB  - The fact that exercise-induced bronchoconstriction (EIB) may be both over- and
      underdiagnosed in athletes has led to calls for widespread screening for the
      condition. This article assesses such a strategy by employing the standard
      framework used when evaluating any screening policy. This approach highlights a
      number of concerns and allows recommendations to help optimize the success of
      such a strategy if it were to be implemented.

PMID- 18046183
TI  - Perivascular fat alters reactivity of coronary artery: effects of diet and
      exercise.
AB  - Perivascular adipose tissue (PAT) has been reported to blunt agonist-induced
      arterial tone via a relaxing factor acting in a paracrine manner. The purpose of
      this study was to test the hypothesis that PAT of porcine coronary artery blunts
      constriction similarly and that this anticontractile effect of PAT is altered by
      diet and/or exercise training. METHODS: Fourteen adult male pigs were fed a
      normal-fat (NF) diet, and 10 adult male pigs were fed a high-fat/cholesterol (HF)
      diet. Four weeks after the initiation of diet, pigs were exercised (EX) or
      remained sedentary (SED) for 16 wk, yielding four groups: 1) NF-SED, 2) NF-EX, 3)
      HF-SED, and 4) HF-EX. Left circumflex coronary artery (LCX) rings were prepared
      with PAT left intact or removed. LCX reactivity to acetylcholine (ACh),
      endothelin (ET-1), bradykinin (BK), and sodium nitroprusside (SNP) was assessed
      in vitro using standard techniques. RESULTS: The results demonstrate that both
      ACh and ET-1 elicited dose-dependent increases in tension from LCX rings from all
      groups. Removal of PAT had no significant effect on ACh-induced contractions in
      any group. In contrast, removal of PAT increased ET-1-induced tension in LCX from
      NF-SED, HF-SED, and HF-EX but not NF-EX. PAT had no significant effect on
      relaxation responses to BK except in HF-EX animals, where removal of PAT
      increased BK-induced relaxation. PAT removal decreased SNP-induced relaxation in
      HF-LCX, but not LCX from NF pigs, suggesting basal release of a relaxing factor
      LCX from HF pigs. CONCLUSION: PAT blunts contractions induced by ET-1 in LCX from
      NF and HF pigs. Whereas EX abolished this effect of PAT in NF pigs, exercise did
      not alter the anticontractile effect in HF pigs.

PMID- 18046185
TI  - A single session of resistance exercise induces oxidative damage in untrained
      men.
AB  - PURPOSE: During exercise, the production of reactive oxygen and nitrogen species
      significantly increases. The aim of the present study was to investigate the
      effects of a single session of resistance exercise on antioxidant capacity,
      oxidative damage, and inflammation. METHODS: Muscle biopsies, urine, and blood
      samples were collected from seven healthy men before and after a single bout of
      resistance exercise. RESULTS: A single session of resistance exercise was found
      to induce oxidative damage, as shown by a 40% increase in the concentration of
      urinary F2alpha-isoprostanes (P < 0.05). Total antioxidant capacity of plasma
      increased 16% (P < 0.05). This increase seemed to be predominantly attributable
      to an increase in plasma uric acid concentrations of 53% (P < 0.05). Similar to
      uric acid, but to a relatively much smaller extent, vitamin C and vitamin E
      levels in plasma were also elevated (P < 0.05). Moreover, the erythrocyte
      glutathione (GSH) [corrected] concentration increased 47% during exercise (P <
      0.05). Also in skeletal muscle, uric acid levels were found to increase after
      exercise (P < 0.05). Moreover, 30 min after exercise, skeletal muscle glutathione
      S-transferase (GST) and glutathione reductase activity increased 28 and 42%,
      respectively (P < 0.05). Skeletal muscle reduced GSH [corrected] and GSH
      [corrected] disulphide (GSSG) concentrations were not affected by exercise. The
      Nuclear Factor kappa B (NF-kappaB) activity in peripheral blood mononuclear cells
      (PBMC) was not increased by exercise, indicating that a NF-kappaB-mediated
      inflammatory response does not occur. CONCLUSION: We conclude that a single
      session of resistance exercise induces oxidative damage despite an adaptive
      increase in antioxidant capacity of blood and skeletal muscle.

PMID- 18046184
TI  - Effect of high-frequency resistance exercise on adaptive responses in skeletal
      muscle.
AB  - PURPOSE: Regulation of skeletal muscle mass is highly dependent on contractile
      loading. The purpose of this study was to examine changes in growth factor and
      inflammatory pathways following high-frequency resistance training. METHODS:
      Using a novel design in which male Sprague-Dawley rats undertook a "stacked"
      resistance training protocol designed to generate a summation of transient
      exercise-induced signaling responses (four bouts of three sets x 10 repetitions
      of squat exercise, separated by 3 h of recovery), we determined the effects of
      high training frequency on signaling pathways and transcriptional activity
      regulating muscle mass. RESULTS: The stacked training regimen resulted in acute
      suppression of insulin-like growth factor 1 mRNA abundance (P < 0.05) and Akt
      phosphorylation (P < 0.05), an effect that persisted 48 h after the final
      training bout. Conversely, stacked training elicited a coordinated increase in
      the expression of tumor necrosis factor alpha, inhibitor kappa B kinase
      alpha/beta activity (P < 0.05), and p38 mitogen-activated protein kinase
      phosphorylation (P < 0.05) at 3 h after each training bout. In addition, the
      stacked series of resistance exercise bouts induced an increase in p70 S6 kinase
      phosphorylation 3 h after bouts x3 and x4, independent of the phosphorylation
      state of Akt. CONCLUSIONS: Our results indicate that high resistance training
      frequency extends the transient activation of inflammatory signaling cascades,
      concomitant with persistent suppression of key mediators of anabolic responses.
      We provide novel insights into the effects of the timing of exercise-induced
      overload and recovery on signal transduction pathways and transcriptional
      activity regulating skeletal muscle mass in vivo.

PMID- 18046186
TI  - Effect of resistance training on immunological parameters of healthy elderly
      women.
AB  - PURPOSE: To determine the effect of a 12-month moderate resistance training
      program on phenotypic and functional immunological parameters of previously
      sedentary, clinically healthy, elderly women. METHODS: A total of 42 clinically
      healthy, sedentary females (aged 60-77 yr old) were randomly assigned to either a
      moderate-intensity resistance training program or a control group during a 12
      month longitudinal, randomized, controlled, intervention study. Resistance
      training program consisted of three sets of 12 repetitions at 54.9 +/- 2.4% 1RM
      for five different exercises performed three times per week during 12 months.
      Natural killer cell cytotoxic activity (NKCA), lymphoproliferative response to
      the mitogen phytohemaglutinin (PHA), and quantification of the lymphocytes (CD3,
      CD3CD19, CD56) and subpopulations (CD4, CD8, CD56, CD56) as well as cellular
      expression molecules (CD25, CD28, CD45RA, CD45RO, CD69, CD95, HLA-DR) were
      determined by immunological assays. RESULTS: The experimental group increased
      muscle strength in 44% and 48% after 6 and 12 months, respectively (P < 0.05).
      There were no statistically significant differences between the groups or
      according to the time for quantitative (CD3, CD3CD19, CD56, CD4, CD8, CD45RA,
      CD45RO, CD56, CD56, CD95, CD28, CD25, CD69, HLA-DR) and functional immunological
      parameters (natural killer cell cytotoxic activity and lymphoproliferative
      response). CONCLUSION: A 12-month moderate resistance training program increases
      muscle strength, but it does not change immune phenotypic and functional
      parameters of previously sedentary, clinically healthy, elderly women.

PMID- 18046187
TI  - Substrate source use in older, trained males after decades of endurance training.
AB  - PURPOSE: The purpose of this study was to compare substrate source use in older,
      long-term exercising, endurance-trained males with sedentary controls. METHODS:
      [U-C]palmitate and [6,6-H2]glucose tracers were applied to assess plasma free
      fatty acid (FFA) and glucose oxidation rates, and to estimate muscle- and/or
      lipoprotein-derived triacylglycerol (TG) and muscle glycogen use. Subjects were
      10 long-term exercising, endurance-trained males and 10 sedentary controls (age
      57 +/- 1 and 60 +/- 2 yr, respectively). Muscle biopsy samples were collected
      before and after exercise to assess muscle fiber type-specific intramyocellular
      lipid and glycogen content. RESULTS: During exercise, plasma palmitate Ra, Rd,
      and Rox were significantly greater in the trained subjects compared with the
      controls (Ra: 0.36 +/- 0.02 and 0.25 +/- 0.02; Rd: 0.36 +/- 0.03 and 0.24 +/-
      0.02; Rox: 0.31 +/- 0.02 and 0.20 +/- 0.02 mmol.min, respectively, P < 0.01).
      This resulted in greater plasma FFA and total fat oxidation rates in the trained
      versus sedentary subjects (P < 0.001). Muscle- and/or lipoprotein-derived TG use
      contributed 10 +/- 2 and 11 +/- 3% in the trained and control groups,
      respectively (NS). No significant net changes in muscle fiber lipid content were
      observed. CONCLUSIONS: Older, endurance-trained males oxidize more fat during
      moderate-intensity exercise than do sedentary controls. This greater total fat
      oxidation rate is attributed to a higher plasma FFA release, uptake, and
      oxidation rate. In contrast, intramyocellular triacylglycerol does not seem to
      represent a major substrate source during 1 h of moderate-intensity exercise in
      older trained or sedentary men.

PMID- 18046188
TI  - Exogenous carbohydrate spares muscle glycogen in men and women during 10 h of
      exercise.
AB  - PURPOSE: The purpose of the study was to evaluate the effects of carbohydrate
      (CHO) supplementation on whole-body and net muscle substrate use during 10 h of
      discontinuous exercise, simulating occupational settings in men and women.
      METHODOLOGY: Recreationally trained subjects (N = 7 males, N = 6 females)
      performed a graded exercise test on a treadmill (TM) and cycle ergometer (CE) to
      determine ventilatory threshold (VT) and V O2peak. In a double-blind, randomized
      crossover design, subjects received either CHO [20% maltodextrin (0.6 g.kg
      FFM.h)] or flavored placebo (PLA) drink each hour across 10 h of exercise.
      Exercise intensity was 71.3 +/- 3% and 72.4 +/- 4% VT for TM and CE,
      respectively. Hourly exercise included 9 min of upper-body ergometery, 19 min of
      cycling, and 20 min of treadmill walking, with a 1-min transition between modes,
      followed by a 10-min rest and feeding period. The protocol was selected to
      simulate arduous occupational settings. Vastus lateralis biopsies were obtained
      before and after exercise. Expired gases were collected every other hour to
      establish average rates of whole-body CHO and fat oxidation. Blood glucose (BG)
      was measured continuously. RESULTS: Whole-body CHO oxidation was maintained
      during CHO trial compared with the PLA trial. Net muscle glycogen use was 52%
      higher for the PLA trial (176.0 +/- 16.7, 117.0 +/- 20.9 and 164.5 +/- 11.0,
      133.8 +/- 10.9 mmol.kg w.w. for PLA and CHO, respectively, P < 0.05). There were
      no significant sex-specific differences in glycogen use, whole-body substrate
      oxidation, or BG values. CONCLUSION: The ingestion of CHO during long-duration
      exercise decreases net muscle glycogen use while better maintaining whole-body
      carbohydrate oxidation, and potentially increasing performance in field settings.
      There are limited differences in sex-specific substrate oxidation.

PMID- 18046189
TI  - Comparison of two methods to assess PAEE during six activities in children.
AB  - PURPOSE: The purpose of this study was to compare the accuracy of physical
      activity energy expenditure (PAEE)-prediction models using accelerometry alone
      (ACC) and accelerometry combined with heart rate monitoring (HR+ACC) to estimate
      PAEE during six common activities in children (lying, sitting, slow and brisk
      walking, hop-scotch, running). Three PAEE-prediction models derived using the
      current data, and five previously published prediction models were cross
      validated to estimate PAEE in this sample. METHODS: PAEE was assessed using ACC,
      HR+ACC, and indirect calorimetry during six activities in 145 children (12.4 +/-
      0.2 yr). One ACC and two HR+ACC PAEE-prediction models were derived using linear
      regression on data from the current study. These three new models were cross
      validated using a jackknife approach, and a modified Bland-Altman method was used
      to assess the validity of all eight models. RESULTS: PAEE predictions using the
      one ACC and two HR+ACC models derived in the current study correlated strongly
      with measured values (RMSE = 97.3-118.0 J.min.kg). All five previously published
      models agreed well overall (RMSE = 115.6-245.3 J.min.kg), but systematic error
      was present for most of these, to a greater extent for ACC. CONCLUSIONS: ACC and
      HR+ACC can both be used to predict overall PAEE during these six activities in
      children; however, systematic error was present in all predictions. Although both
      ACC and HR+ACC provide accurate predictions of overall PAEE, according to the
      activities in this study, PAEE-prediction models using HR+ACC may be more
      accurate and widely applicable than those based on accelerometry alone.

PMID- 18046191
TI  - Assessment of change in body fat percentage with DXA and eight-electrode BIA in
      centrally obese women.
AB  - PURPOSE: To compare estimates of change in percent body fat (Delta%BF) between
      DXA and BIA8 in abdominally obese women. METHODS: Six-month longitudinal study of
      106 women (baseline: age 48.2 +/- 7.6 yr; BMI 30.4 +/- 2.9 kg.m; %BFDXA 45.8 +/-
      3.6%) participating in an exercise-oriented behavior-change program (walking and
      bicycling). Fatness was measured by DXA and Tanita BC-418 (BIA8). Agreement
      between methods was assessed, and regression analysis was used to find predictors
      of the deviation between methods for estimating changes in fat mass percentage.
      RESULTS: The methods differed significantly, both at baseline and follow-up (-5.0
      and -4.4%BF, respectively; both P < 0.001). The mean Delta%BF was -1.1 +/-
      2.5%BFDXA and -0.5 +/- 2.2%BFBIA8 (mean difference between methods 0.6 +/-
      1.8%BF; P < 0.001; 95% limits of agreement -3.0 to 4.2%BF), with a range of -14.8
      to 3.3%BFDXA and -9.4 to 3.5%BFBIA8. Approximately 49% of the variation in the
      difference between methods was explained by variations in age (beta = -0.05; P =
      0.006), DeltaBMI (beta = 0.98; P < 0.001), and Delta%BFDXA (beta = -0.71; P <
      0.001), indicating that the larger the change, the greater the discrepancy
      between methods. CONCLUSION: The difference between methods regarding Delta%BF
      was statistically significant, but it was of small magnitude. However, with
      increasing Delta%BF, increasing discrepancies were observed, implying that the
      BIA equipment may have limited validity for detecting larger fat losses. Both
      clinicians and researchers may benefit from awareness of this potential
      limitation.

PMID- 18046190
TI  - Quantifying leisure physical activity and its relation to bone density and
      strength.
AB  - PURPOSE: Compare three published methods of quantifying physical activity (total
      activity, peak strain, and bone-loading exposure (BLE) scores) and identify their
      associations with areal bone mineral density (aBMD), volumetric BMD (vBMD), and
      bone strength. METHODS: Postmenopausal women (N = 239; mean age: 53.8 yr) from
      Iowa (ISU) and California (UCD) completed the Paffenbarger Physical Activity
      Questionnaire, which was scored with each method. Dual energy x-ray
      absorptiometry assessed aBMD at the spine, hip, and femoral neck, and peripheral
      quantitative computed tomography (pQCT) measured vBMD and bone strength
      properties at the distal tibia and midshaft femur. RESULTS: UCD women had higher
      total activity scores and hours per week of leisure activity. All scoring methods
      were correlated with each other. No method was associated with aBMD. Peak strain
      score was negatively associated with polar moment of inertia and strength-strain
      index at the tibia, and total activity score was positively associated with
      cortical area and thickness at the femur. Separating by geographic site, the peak
      strain and hip BLE scores were negatively associated with pQCT measures at the
      tibia and femur among ISU subjects. Among UCD women, no method was significantly
      associated with any tibia measure, but total activity score was positively
      associated with measures at the femur (P < 0.05 for all associations).
      CONCLUSION: Given the significantly greater hours per week of leisure activity
      done by UCD subjects, duration may be an important determinant of the effect
      physical activity has on bone. The positive association between leisure physical
      activity (assessed by the total activity score) and cortical bone measures in
      postmenopausal women may indicate a lifestyle factor that can help offset age
      related bone loss.

PMID- 18046192
TI  - Biodynamics. Influence of gender, power, and hand position on pelvic motion
      during seated cycling.
AB  - INTRODUCTION/PURPOSE: An understanding of normal pelvic motion during seated
      cycling is relevant to saddle design and bicycle fitting. In this study, we
      investigated the effects of gender, power, and hand position on pelvic motion
      throughout a pedal stroke. We also investigated whether anthropometric factors
      could explain any interindividual differences observed. METHODS: Twelve
      experienced male and 14 experienced female cyclists participated. Each subject
      was custom fitted to a stationary bicycle and then rode the bicycle at three
      power outputs (100, 150, and 200 W), with their hands in the tops and drops
      position. The kinematics of a triad of motion-capture markers, located on
      posterior pelvic landmarks, were used to characterize pelvic motion. RESULTS: The
      largest angular excursions were observed in the nonsagittal planes, with the
      pelvis rotating internally (approximately 3 degrees ) and rolling laterally (
      approximately 2 degrees ) toward the downstroke. These pelvic rotations caused
      the hip on the downstroke side to translate anteriorly and inferiorly. Compared
      with males, females exhibited greater average anterior pelvic tilt in the drops
      hand position (males: 21 +/- 3 degrees ; females: 24 +/- 4 degrees ; P = 0.036).
      Interindividual differences in pelvic motion could not be independently explained
      by measures of ischial tuberosity width or hamstring flexibility. However,
      average anterior pelvic tilt was negatively correlated with lumbar flexibility
      among the males (r = 0.75; P = 0.024), suggesting that this may be an important
      factor to consider in bicycle fitting. CONCLUSIONS: We observed substantial
      pelvic motion during seated cycling, with experienced female road cyclists
      exhibiting greater average anterior tilt than their male counterparts. Pelvic
      motion seems to arise naturally during seated cycling and should be considered
      when designing saddles and establishing bicycle-fitting procedures.

PMID- 18046193
TI  - Biodynamics. Effect of pacing strategy on energy expenditure during a 1500-m
      cycling time trial.
AB  - PURPOSE: A critical assumption in modeling optimal pacing strategy is that the
      amount of anaerobic energy that can be produced during a time trial is a constant
      value, independent of pacing strategy. To test this assumption, the effect of
      manipulations of pacing strategy on anaerobic work produced during a 1500-m
      cycling time trial was studied. Additionally, the effect of pacing strategy on
      aerobic and total work was studied. METHODS: Nine well-trained cyclists performed
      three 1500-m cycle ergometer time trials with different strategies (conservative
      (SUB), even paced (EVEN), and aggressive (SUPRA)). Anaerobic work, aerobic work,
      and total work were calculated on the basis of V O2, RER, gross efficiency, and
      external power output. RESULTS: ANOVA showed that total anaerobic work did not
      differ per strategy (EVEN: 27,604 +/- 1103 J, SUB: 26,495 +/- 1958 J, and SUPRA:
      26,949 +/- 2062 J). No differences in aerobic work (EVEN: 28,266 +/- 1623 J,SUB:
      27,950 +/- 1418 J, SUPRA: 27,844 +/- 1965 J) were evident, either. Subjects were
      able to accomplish significantly (P < 0.05) more total work during EVEN (55,870
      +/- 2245 J) than during SUB and SUPRA (54,444 +/- 2306 and 54,794 +/- 2402 J,
      respectively). CONCLUSION: No difference in anaerobic and aerobic work was found
      per pacing strategy. Though relevant for sports performance, the differences in
      total work were relatively small (approximately 2%), considering the broad range
      of imposed strategies. The assumption that anaerobic work is a constant value,
      independent of pacing strategy, seems valid in the range of different strategies
      that are currently simulated in the energy flow models.

PMID- 18046194
TI  - Physical fitness and performance. Fatigue responses during repeated sprints
      matched for initial mechanical output.
AB  - PURPOSE: To compare muscle fatigability during two sets of repeated cycling
      sprints matched for initial mechanical output in a nonfatigued and fatigued
      state. METHODS: Eight young men performed 10, 6-s all-out sprints on a cycle
      ergometer interspersed with 30 s of recovery, followed, after 6 min of passive
      recovery, by five 6-s sprints, again interspersed by 30 s of recovery. RESULTS:
      On the basis of total work (TW), performance in sprint 11 (79.8 +/- 4.8 J.kg) was
      not significantly different to performance in sprint 4 (80.3 +/- 5.3 J.kg; P =
      0.81). The decrease in TW for the five sprints after sprint 4 (i.e., sprints 4 to
      8) averaged 14.5% (P < 0.001), which was significantly less than the decrement in
      TW from sprints 11 to 15 (20.3%; P < 0.05). Despite no significant differences in
      TW values achieved in sprints 4 and 11, the amplitude of the electromyogram (EMG)
      signal (i.e., root mean square (RMS)) recorded during sprint 11 (0.398 +/- 0.03
      V) was 12.0% lower (P < 0.05) than in sprint 4 (0.452 +/- 0.02 V). In contrast,
      values of EMG median frequency (MF) recorded during sprint 4 (85.5 +/- 5.5 Hz)
      and 11 (89.3 +/- 7.2 Hz) were not significantly different (P = 0.33). However,
      the rate of decrease in EMG activity (i.e., RMS and MF) was similar for the two
      set of sprints. CONCLUSIONS: These findings suggest that previous fatiguing
      repeated-sprint exercise, followed by a rest period, induces greater fatigability
      during subsequent repeated-sprint exercise, regardless of the initial mechanical
      output, and that these changes are associated with acute neuromuscular
      adjustments.

PMID- 18046195
TI  - Physical fitness and performance. Training for old age: production functions for
      the aerobic exercise inputs.
AB  - PURPOSE: This paper attempts to develop production functions (PF) between aerobic
      exercise inputs and long-run health outputs. Future studies could use such PF for
      estimating the benefits and costs (broadly defined) of different exercise
      programs to help develop optimal (utility maximizing) ones. METHODS: To develop
      the PF, the paper reviewed the biomedical literature for the major dose-response
      relations between health, physical fitness, and exercise. Where relevant, the
      paper converted the dose-response relationships from relative risks to absolute
      probabilities and standardized terminology and units of measures. RESULTS: The
      paper develops a clear set of biological PF that illustrate, quantitatively, how
      increases in peak cardiorespiratory (CR) fitness as measured by a short stress
      test reduce the probability of all-cause mortality; how increasing intensities of
      short (approximately 30 min, three to five times a week) exercise sessions
      increase peak CR fitness or retard its age-related decline; and how consistent
      exercise reduces the risk of myocardial infarctions (MI). CONCLUSIONS: The
      exercise-long-run health PF developed in this paper should provide a useful
      framework for other studies to estimate the broadly defined costs and benefits of
      different exercise programs and to help develop optimal ones.

PMID- 18046196
TI  - Physical fitness and performance. Cardiorespiratory fitness in girls-change from
      middle to high school.
AB  - PURPOSE: To determine how factors are related to change in cardiorespiratory
      fitness (CRF) across time in middle school girls followed through high school.
      METHODS: Adolescent girls (N = 274, 59% African American, baseline age = 13.6 +/-
      0.6 yr) performed a submaximal fitness test (PWC170) in 8th, 9th, and 12th
      grades. Height, weight, sports participation, and physical activity were also
      measured. Moderate-to-vigorous physical activity (MVPA) and vigorous physical
      activity (VPA) were determined by the number of blocks reported on the 3-Day
      Physical Activity Recall (3DPAR). Individual differences and developmental change
      in CRF were assessed simultaneously by calculating individual growth curves for
      each participant, using growth curve modeling. RESULTS: Both weight-relative and
      absolute CRF increased from 8th to 9th grade and decreased from 9th to 12th
      grade. On average, girls lost 0.16 kg.m.min.kg.yr in weight-relative PWC170
      scores (P < 0.01) and gained 10.3 kg.m.min.yr in absolute PWC170 scores. Girls
      reporting two or more blocks of MVPA or one or more blocks of VPA at baseline
      showed an average increase in PWC170 scores of 0.40-0.52 kg.m.min.kg.yr (weight
      relative) and 22-28 kg.m.min.yr (absolute) in CRF. In weight-relative models,
      girls with higher BMI showed lower CRF (approximately 0.37 g.m.min.kg.yr), but
      this was not shown in absolute models. In absolute models, white girls
      (approximately 40 kg.m.min.yr) and sport participants (approximately 28
      kg.m.min.yr) showed an increase in CRF over time. CONCLUSION: Although there were
      fluctuations in PWC170 scores across time, average scores decreased during 4 yr.
      Physical activity was related to change in CRF over time; BMI, race, and sport
      participation were also important factors related to change over time in CRF
      (depending on expression of CRF-weight-relative vs absolute). Subsequent research
      should focus on explaining the complex longitudinal interactions between CRF,
      physical activity, race, BMI, and sports participation.

PMID- 18046197
TI  - Physical fitness and performance. Body composition by DEXA and its association
      with physical fitness in 140 conscripts.
AB  - PURPOSE: The aim of the study was to determine the body composition of healthy
      young men and to investigate whether there exists an association between body
      composition and physical fitness. MATERIALS AND METHODS: A prospective cohort
      study of 140 healthy male conscripts (mean age 19.8yr, SD 1.0 yr) was conducted.
      We examined subject characteristics, aerobic performance, and muscle strength,
      and we assessed body composition using dual-energy x-ray absorptiometry (DEXA).
      The association between total body composition and lower-limb composition and
      physical performance was investigated by linear regression. RESULTS: The mean
      body mass index (BMI) of the subjects was 24.6 kg.m (SD 4.7). Their mean bone
      mineral density (BMD) was 1.3 g.cm (SD 0.1), fat percentage (fat%) 22.6 (SD 9.7),
      lean mass 57.6 kg (SD 7.0), and bone mass 3.2 kg (SD 0.4) at the beginning of the
      military service. Fat percentage was significantly associated with 12-min running
      performance (P < 0.001), and a significant relationship was found between muscle
      strength and fat% (P< 0.001), and increasing BMD (P < 0.001), in multivariate
      analysis. Lean mass was not associated with physical performance. CONCLUSIONS:
      DEXA measurement of the proportion of body fat is a useful tool to indirectly
      assess running performance and muscle strength in Finnish male conscripts.
      Increased fat mass and fat percentage were strong predictors of poorer physical
      fitness. Moreover, the relationship between muscle strength and BMD was
      confirmed. However, muscle mass did not predict muscle strength in our sample.

PMID- 18046198
TI  - Psychobiology and behavioral strategies. Physical activity, sport participation,
      and suicidal behavior: U.S. high school students.
AB  - PURPOSE: To evaluate the associations of physical activity and sports team
      participation with suicidal behavior among U.S. high school students. METHODS:
      Data were from the 2003 Youth Risk Behavior Survey (N = 10,530 respondents).
      Exposure variables included physical activity (inactive, insufficient, moderately
      intensive, regular vigorously intensive, and frequent vigorously intensive) and
      sports team participation. Outcome variables were suicide ideation (seriously
      considering and/or planning suicide) and suicide attempts. Hierarchical logistic
      regressions were run, controlling for age, race, smoking, alcohol use, drug use,
      geographic region, unhealthy weight-control practices, and body mass index/weight
      perceptions. RESULTS: Compared with inactive students or sports team
      nonparticipants, the odds of suicide ideation were lower among boys reporting
      frequent vigorous-intensity physical activity (adjusted odds ratio (AOR) = 0.48;
      95% confidence interval (CI) = 0.29, 0.79) and sports team participation,
      respectively (AOR = 0.65; 95% CI = 0.48, 0.86). The odds of suicide attempts were
      also lower among frequently vigorously active boys (AOR = 0.44; 95% CI = 0.21,
      0.96) and sports team participants (AOR = 0.61; 95% CI = 0.40, 0.93). The odds of
      suicide attempts were lower for regular vigorously active girls compared with
      inactive girls (AOR = 0.67; 95% CI = 0.45, 0.99) and sports team participants
      compared with nonparticipants (AOR = 0.73; 95% CI = 0.57, 0.94). Associations
      with one exposure variable generally weakened when adjustment was made for the
      other exposure variable, or for feeling sad and hopeless. CONCLUSIONS: The
      association of physical activity and sports team participation with suicide
      ideation and suicide attempts varied by sex. Further research is needed to
      clarify these different associations.

PMID- 18046200
TI  - Women and heart disease: what's new?
AB  - Find out by reading this analysis of the new AHA guidelines for assessing and
      managing risk.

PMID- 18046201
TI  - Patient-teaching for cardiac nurses.
AB  - These sites offer a wide variety of materials. Here's just a sampling.

PMID- 18046202
TI  - Identifying second-degree atrioventricular block (type I).

PMID- 18046203
TI  - The natural art of networking.

PMID- 18046204
TI  - NAON Foundation...are you lighting the fire?

PMID- 18046205
TI  - Kyphoplasty. A treatment for osteoporotic vertebral compression fractures.
AB  - Patients experience more than 700,000 osteoporotic vertebral compression
      fractures each year in the United States, primarily because of bone brittleness
      and the inability of the vertebrae to resist increased forces applied to them.
      Patients diagnosed with this type of fracture are given the option of
      conservative or operative treatment approaches. Although a typical compression
      fracture generally heals in 6 to 12 weeks, patients may be offered the
      kyphoplasty procedure, which reduces the fracture and stabilizes it with cement.
      Although this procedure is not without risk, it is deemed a safe and effective
      treatment option. This article reviews the indications, implications, and care
      provided to patients pursuing kyphoplasty after osteoporotic vertebral
      compression fracture.

PMID- 18046207
TI  - Congenital coxa vara deformity.

PMID- 18046209
TI  - Delirium in the orthopaedic patient.
AB  - Published incidence of delirium in orthopaedic patients ranges from 5.1% to 61%.
      Delirium may present before or after the patient undergoes the surgical procedure
      and has demonstrated increased risk, including mortality. Yet, delirium goes
      unrecognized by both physicians and nurses. This article focuses on the
      literature on delirium in the orthopaedic patient, including incidence, how to
      identify those patients at risk, patient outcomes, nonpharmacological and
      pharmacological interventions, and provides an example of how one tertiary care
      hospital implemented a prevention and management program of delirium in
      orthopaedic patients.

PMID- 18046211
TI  - Motivating an intergenerational workforce: scenarios for success.
AB  - Although much has been written about the challenge of having four generations in
      the workplace simultaneously, problems of conflict, misunderstanding, and
      divisiveness continue. This article provides a snapshot of each generation as
      context. A series of scenarios based on Maslow's Hierarchy of Needs are then
      presented with insights into how each generation might approach the situation,
      along with hints for successfully managing toward positive outcomes. The expected
      outcome is a technique for each generation to look at workplace situations from
      all perspectives.

PMID- 18046213
TI  - Postoperative benefits of intrathecal injection for patients undergoing total
      knee arthroplasty.
AB  - PURPOSE: The purpose of the study was to compare postoperative outcomes in
      patients undergoing total knee replacement via general anesthesia with patients
      receiving an intrathecal injection for anesthesia. DESIGN: A two-group comparison
      design was selected to differentiate pain control, ambulation distance, and
      length of hospital stay in total knee arthroplasty patients. SAMPLE: A random
      sample of 85 patients receiving a total knee arthroplasty by the same surgeon
      were selected. Forty-four patients received general anesthesia, and 41 patients
      received an intrathecal injection. FINDINGS: The overall effect of pain control
      was greater in patients with intrathecal injections up to 48 hours after arrival
      on the orthopedic unit. Ambulation distance was greater for intrathecal patients
      for the first three therapy sessions. IMPLICATIONS FOR NURSING PRACTICE: The use
      of an intrathecal injection for pain management changes postoperative nursing
      care planning and interventions. Improved pain control results in more alert and
      responsive patients and earlier ambulation. Patient teaching for prevention of
      complications and self-care postdischarge can begin earlier.

PMID- 18046214
TI  - The frail elderly: a matter of caring.
AB  - Nurses caring for patients with orthopaedic problems often encounter elderly
      patients in their caseload. These patients have variable levels of functioning;
      some may be frail and, therefore, require greater assistance and possibly more
      time with their care. This loss of function and need for more assistance
      increases their vulnerability and creates challenges for nurses and other
      healthcare providers who are delivering patient care. This article offers a brief
      description of the frail elderly and examines their increasing vulnerability and
      their need for additional protection, preserving their dignity and respecting
      their autonomy, and how caring helps to guide nurses in addressing the special
      needs of this particularly vulnerable patient population. Sensitivity, patience,
      trust, compassion, and clinical competence matter when caring for the frail
      elderly.

PMID- 18046215
TI  - Heparin-induced thrombocytopenia.
AB  - Each year, 25% of all hospitalized patients are affected by venous
      thromboembolism, a disease comprising deep vein thrombosis and pulmonary
      embolism, that is responsible for up to 10% of all inpatient deaths (Alikhan,
      Peters, Wilmott, Cohen, 2004). Used in both the treatment and the prevention of
      venous thromboembolism, heparin is administered to more than 12 million patients
      each year in the United States, making it one of the most widely prescribed
      medications and the leading intravenous anticoagulant. Heparin-induced
      thrombocytopenia is an antibody-mediated adverse drug reaction to heparin therapy
      with potentially life-threatening complications. This article discusses the
      pathogenesis, diagnosis, and treatment of patients with heparin-induced
      thrombocytopenia.

PMID- 18046218
TI  - Avastin versus Lucentis: ethical issues in treatment of age-related macular
      degeneration.

PMID- 18046219
TI  - Cheap shots and pricey propositions: evidence, disclosure, and treatment of age
      related macular degeneration.

PMID- 18046220
TI  - The natural history of pigment epithelial detachment associated with central
      serous chorioretinopathy.
AB  - PURPOSE: To determine the visual outcome of retinal pigment epithelial detachment
      (PED) associated with central serous chorioretinopathy (CSC), to further
      characterize the natural history of these lesions, and to provide a review of
      previous reports. PARTICIPANTS: Data for 340 consecutive patients with a
      diagnosis of CSC from January 2001 through December 2004 were retrospectively
      reviewed. Patients with CSC combined with angiographic evidence of PED were
      included in the study. MAIN OUTCOME MEASURES: Age, sex, use of corticosteroid
      medications, presenting visual acuity, and final visual acuity were recorded.
      Lesion characteristics including location, number of lesions, and laterality were
      recorded. Clinical outcome measures included resolution or persistence of the
      PED, progression to retinal pigmentary atrophy, or development of choroidal
      neovascularization. Fluorescein angiograms were obtained if available. RESULTS:
      Thirty-four (9%) of 319 patients with angiographic evidence of CSC were diagnosed
      with PED over a mean follow-up of 49 months (range, 12-165 months; median, 36
      months). Mean age of the patients was 47 years (range, 32-69 years; median, 48
      years), most of whom were males (68%). Mean initial visual acuity was 20/32
      (range, 20/13 to 20/400; median, 20/30). PEDs were commonly unilateral (88%),
      unifocal (76%), and extrafoveal (82%). Overall mean final visual acuity was 20/25
      (range, 20/13 to 20/250; median, 20/25) for all patients. Mean visual acuity for
      the group of patients with subfoveal PED (18%) was 20/50 (range, 20/25 to 20/250;
      median, 20/50). Complete resolution of the PED occurred in 65% of patients, with
      resultant mean visual acuity of 20/25 (range, 20/13 to 20/250; median, 20/25). In
      this group, localized retinal pigment epithelial atrophy developed in 86%, with
      mean final visual acuity of 20/25 (range, 20/13 to 20/250; median, 20/25).
      Persistent PED was observed in 35% of patients, resulting in mean visual acuity
      of 20/25. There were no cases of choroidal neovascularization. CONCLUSIONS: CSC
      with associated retinal PED may be seen and generally has a good visual
      prognosis. The most frequent outcome is resolution with retinal pigment
      epithelial atrophy. Subfoveal PED occurs less commonly and may have a poorer
      visual prognosis.

PMID- 18046221
TI  - Multifocal choroiditis with panuveitis and punctate inner choroidopathy:
      comparison of clinical characteristics at presentation.
AB  - PURPOSE: To compare the clinical characteristics at presentation of multifocal
      choroiditis with panuveitis (MFCPU) and punctate inner choroidopathy (PIC).
      METHODS: A cross-sectional study of 66 patients (122 eyes) with MFCPU and 13
      patients (22 eyes) with PIC was carried out. Diagnosis was based solely on
      retinal morphology. Demographic information, visual acuity at presentation, and
      presence of intraocular inflammation, choroidal neovascularization (CNV), and
      structural complications of intraocular inflammation (including cataract, cystoid
      macular edema [CME], and epiretinal membrane [ERM]) were compared for the two
      groups. RESULTS: The median ages at presentation of patients with MFCPU and PIC
      were 45 years and 29 years, respectively (P = 0.007). At presentation, patients
      with MFCPU had a higher frequency of structural complications, such as cataract
      (31.6%), CME (13.6%), and ERM (4.6%). Patients with PIC had none of these
      complications. Although CNV occurred more frequently in patients with PIC (PIC,
      76.9%; MFCPU, 27.7%; P = 0.002), those with MFCPU were more likely to have
      bilateral visual impairment of 20/50 or worse (MFCPU, 20%; PIC, 0; P = 0.03).
      CONCLUSION: PIC and MFCPU appeared to have different clinical characteristics at
      presentation. Patients with PIC had a higher frequency of CNV at presentation but
      lower frequencies of structural complications from intraocular inflammation and a
      lower frequency of visual impairment at presentation.

PMID- 18046222
TI  - Intravitreal bevacizumab (avastin) injection as primary treatment of inflammatory
      choroidal neovascularization.
AB  - OBJECTIVE: To assess the effects of intravitreal bevacizumab injection as primary
      treatment of inflammatory choroidal neovascularization (CNV). METHODS: Data for
      nine consecutive patients with newly diagnosed inflammatory CNV who were treated
      with intravitreal bevacizumab (1.25 mg) injection were reviewed retrospectively.
      Main outcome measures were best-corrected visual acuity, foveal thickness
      measured by optical coherence tomography (OCT), and complete resolution of CNV.
      RESULTS: CNV resolved completely in 9 (100%) of 9 affected eyes. At the last
      examination, visual acuity was improved in 8 eyes (88.8%), stable in 1 (11.2%),
      and worse in 0. Over a mean follow-up of 7.1 months (range, 6-10 months), 7 eyes
      received 1 injection, 1 eye developed CNV recurrence and required a second
      injection, and 1 eye required a third injection. Foveal thickness by OCT
      decreased significantly (P = 0.049) after treatment. CONCLUSION: In this small
      case series of eyes with limited follow-up, intravitreal bevacizumab injection
      for treatment of inflammatory CNV was found to be safe and was associated with
      favorable visual outcomes for both subfoveal and juxtafoveal or extrafoveal
      inflammatory CNV.

PMID- 18046223
TI  - Intravitreal bevacizumab (avastin) injection alone or combined with triamcinolone
      versus macular photocoagulation as primary treatment of diabetic macular edema.
AB  - PURPOSE: To report the efficacy of a single intravitreal bevacizumab injection
      alone or in combination with intravitreal triamcinolone acetonide versus macular
      laser photocoagulation (MPC) as primary treatment of diabetic macular edema
      (DME). METHODS: In this randomized, three-arm clinical trial, 103 eyes of 97
      patients with clinically significant DME and no previous treatment were enrolled.
      The eyes were randomly assigned to one of three study arms: the intravitreal
      bevacizumab (IVB) group, patients who received 1.25 mg of intravitreal
      bevacizumab (37 eyes); the IVB/IVT group, patients who received 1.25 mg of
      intravitreal bevacizumab and 2 mg of intravitreal triamcinolone (33 eyes); and
      the MPC group, patients who underwent focal or modified grid laser (33 eyes).
      Primary outcome measure was change in visual acuity. RESULTS: Visual acuity
      changes +/- SD at 12 weeks were -0.22 +/- 0.23, -0.13 +/- 0.31, and + 0.08 +/-
      0.31 logarithm of the minimal angle of resolution in the IVB, IVB/IVT, and MPC
      groups, respectively. The marginal regression model based on generalized
      estimating equation analysis demonstrated that the visual acuity changes in the
      groups were statistically significant at both 6 weeks (P < 0.0001) and 12 weeks
      (P = 0.024). The significant treatment effect was demonstrated at both 6 weeks
      and 12 weeks in the IVB group and only at 6 weeks in the IVB/IVT group.
      Significant central macular thickness (CMT) reduction was observed in eyes in the
      IVB and IVB/IVT groups only up to 6 weeks; however, CMT changes were not
      significant in the groups. CONCLUSION: Up to 12 weeks, intravitreal bevacizumab
      treatment of patients with DME yielded better visual outcome than laser
      photocoagulation, although it was not associated with a significant decrease in
      CMT. No further beneficial effect of intravitreal triamcinolone could be
      demonstrated. Further clinical trials with longer follow-up are required to
      evaluate the long-term visual outcomes and complication profiles after primary
      treatment with such medications.

PMID- 18046224
TI  - Predicted biologic activity of intravitreal bevacizumab.
AB  - PURPOSE: To create a time- and dose-dependent mathematical model that compares
      the intravitreal vascular endothelial growth factor (VEGF) binding activity of
      bevacizumab with that of ranibizumab. METHODS: Intravitreal half-lives and
      relative equimolar VEGF binding activities of bevacizumab and ranibizumab were
      incorporated into a first-order decay model. Time-dependent bevacizumab
      activities (relative to ranibizumab) for different initial doses (1.25 and 2.5
      mg) and reinjection intervals (single, weekly, and every 3 days) were calculated
      and graphed. RESULTS: Twenty-seven days to 38 days after a single bevacizumab
      (1.25 mg) injection, the intravitreal VEGF binding activity would be comparable
      with that of ranibizumab at 30 days. Bevacizumab (2.5 mg) injections would need
      to be performed every 3 days for 1 month to equal the peak activity after a
      ranibizumab injection. DISCUSSION: On the basis of this mathematical model,
      intravitreal bevacizumab maintains significant VEGF binding activity for 4 weeks
      to 5 weeks. More frequent bevacizumab injections increase the average binding
      activity but not to that seen with a single ranibizumab injection.

PMID- 18046225
TI  - Micropulsed laser photocoagulation and intravitreal triamcinolone acetonide
      injection for the treatment of retinal angiomatous proliferation.
AB  - PURPOSE: To investigate visual acuity and fluorescein angiographic outcomes, as
      well as adverse events, associated with treatment of retinal angiomatous
      proliferation (RAP) with micropulsed laser photocoagulation and intravitreal
      triamcinolone acetonide injection. METHODS: In this retrospective,
      noncomparative, interventional, consecutive case series, the medical records of
      all patients treated for RAP with micropulsed laser photocoagulation (yellow or
      green dye; duration, 0.02-0.05 second; power adjusted to achieve a white burn of
      moderate intensity at the level of the RAP lesion in the retina) and intravitreal
      triamcinolone acetonide (4 mg/0.1 mL) injection between January 2003 and November
      2004 were reviewed by one of four retina specialists at a single retina practice.
      Main outcome measures were visual acuity, leakage shown by fluorescein
      angiography, and adverse events. RESULTS: The study included 14 eyes of 13
      patients (8 women and 5 men; median age, 83 years [range, 70-90 years]).
      Triamcinolone acetonide injection preceded laser treatment by a median duration
      of 7 days (range, 5-16 days) in 8 eyes, was performed on the same day as laser
      treatment in 2 eyes, and followed laser treatment by a median duration of 7 days
      (range, 7-28 days) in 4 eyes. Eyes were followed a median of 18 months (range, 12
      27 months) after treatment with both laser and intravitreal triamcinolone
      injection. Compared with pretreatment visual acuity, vision at 12 months and the
      last follow-up examination was stable in 5 eyes (36%), improved by >or=2 lines in
      6 eyes (43%), and worsened by >or=2 lines in 3 eyes (21%). The median visual
      acuity before treatment was 20/200 compared with 20/80 at 3 months after
      treatment (P = 0.02), 20/100 at 6 months after treatment (P = 0.16), 20/200 at 12
      months after treatment (P = 0.73), and 20/100 (P = 0.63) at the last follow-up
      examination. For 13 eyes (93%), fluorescein angiography performed 6 months after
      administration of both laser and intravitreal triamcinolone injection
      demonstrated resolution of all leakage; one eye was treated with photodynamic
      therapy with verteporfin 6 months after treatment for persistent low-grade
      leakage. Elevated intraocular pressure (>25 mm Hg) occurred in 2 eyes at 2.5
      months and 2 months after intravitreal triamcinolone acetonide injection; both
      eyes were treated with transient use of antiglaucoma eyedrops. Seven (78%) of 9
      phakic eyes had cataract progression, and 5 of these 7 eyes underwent cataract
      extraction during the follow-up period. No other adverse events occurred.
      CONCLUSIONS: Micropulsed laser photocoagulation and intravitreal triamcinolone
      acetonide injection may be effective and safe treatment for RAP lesions.

PMID- 18046226
TI  - Prospective, randomized clinical trial of intravitreal triamcinolone treatment of
      neovascular age-related macular degeneration: one-year results.
AB  - PURPOSE: To investigate the effect of intravitreal injection of high-dose (20-25
      mg) triamcinolone acetonide on minimally classic or occult choroidal
      neovascularization (CNV) secondary to age-related macular degeneration (AMD).
      METHODS: A prospective, double-masked, placebo-controlled, randomized clinical
      trial included 39 eyes with minimally classic or occult CNV secondary to AMD. The
      treatment group (21 eyes) received intravitreal injection (20-25 mg) of
      triamcinolone acetonide and the control group (18 eyes) received intravitreal
      injection (500 mug) of dexamethasone at 6-month intervals. Best-corrected ETDRS
      (Early Treatment Diabetic Retinopathy Study) score, contrast sensitivity score,
      and central macular volume were measured at 1 month, 3 months, 6 months, and 12
      months. RESULTS: Mean baseline best-corrected visual acuity (BCVA [logarithm of
      the minimal angle of resolution]) was 0.64 (Snellen equivalent, 20/80) in each
      group. At 1 month, 3 months, and 6 months after the injection, neither group had
      a significant change in BCVA. At 12 months, mean BCVA +/- SD significantly
      decreased to 1.06 +/- 0.34 (Snellen equivalent, 20/200) in the treatment group
      (paired t-test, P < 0.001), whereas it was 0.78 +/- 0.52 (Snellen equivalent,
      20/125) in the control group (P = 0.23). The difference was marginally
      significant (P = 0.06, Student's t-test). All phakic eyes in the treatment group
      developed marked cataract progression. CONCLUSIONS: Intravitreal injection of
      high-dose triamcinolone had no beneficial effect on eyes with minimally classic
      or occult CNV secondary to AMD and was associated with outcomes similar to those
      associated with intravitreal injection of dexamethasone, which was used as
      placebo.

PMID- 18046227
TI  - Optical coherence tomography characteristics of group 2A idiopathic parafoveal
      telangiectasis.
AB  - PURPOSE: To describe the optical coherence tomography (OCT) characteristics of
      patients with group 2A idiopathic parafoveal telangiectasis (IPFT) and to
      correlate them with biomicroscopic and fluorescein angiographic (FA) findings
      based on Gass and Blodi staging classification for group 2A IPFT. METHODS: Fifty
      two eyes of 26 consecutive patients with IPFT underwent biomicroscopic fundus
      examination, color fundus photography, FA, and OCT. Main outcome measures were
      OCT characteristics and their correlation with biomicroscopy and FA. RESULTS: The
      most common OCT findings that help differentiate between stages in group 2A IPFT
      are 1) highly reflective dots in the inner retina that correspond with
      microvessels seen by FA in Stage 1 (5 eyes [62.5%]); 2) the presence of
      hyporeflective intraretinal spaces in the absence of retinal thickening and
      highly reflective dots in the retina in Stage 2 (9 [81.8%] and 10 eyes [90.9%],
      respectively); 3) in Stage 3, both outer and inner retina exhibit areas of
      similar high reflectivity. In addition, the retinal pigment epithelium
      (RPE)/choriocapillaris complex is thickened or disrupted as evidenced by an area
      of high reflectivity (13 eyes [81.2%]); 4) a highly reflective area nasal or
      temporal to the fovea in the inner or outer retinal layers in Stage 4 suggesting
      RPE proliferation and migration (13 eyes [100%]); and 5) a fusiform thickening
      and duplication of the highly reflective RPE/choriocapillaris complex
      corresponding to choroidal neovascularization in Stage 5 (4 eyes [100%]). Our OCT
      characteristics correlated well with biomicroscopic and FA findings for Stages 4
      and 5. However, the hyporeflective spaces that are evident on OCT could not be
      seen clinically at the slit lamp or on FA. In addition, our OCT findings on eyes
      with group 2A IPFT Stage 3 have not, to our knowledge, been previously described.
      CONCLUSIONS: Optical coherence tomography findings in group 2A IPFT were
      characteristic for each stage and may be helpful in making the diagnosis as well
      as defining the anatomical staging proposed by Gass and Blodi. Optical coherence
      tomography complements biomicroscopic and FA findings in the evaluation of group
      2A IPFT.

PMID- 18046228
TI  - Foveal dysplasia evident by optical coherence tomography in patients with a
      history of retinopathy of prematurity.
AB  - PURPOSE: To describe the optical coherence tomography (OCT) findings for patients
      with a history of retinopathy of prematurity (ROP). METHODS: Clinical records,
      fundus photographs, and OCT findings for consecutive patients aged 8 years and
      older who had a history of ROP were reviewed. The main outcome measures were best
      corrected visual acuity, central foveal thickness (CFT), macular anatomy, and
      foveal contour by OCT. RESULTS: Twenty eyes of 12 patients (median age, 15 years)
      were studied. Median gestational age at birth was 25 weeks. Six eyes had received
      peripheral retinal ablation for threshold ROP. Median best-corrected visual
      acuity was 20/40 (range, 20/20 to counting fingers). CFT was >220 microm in 70%
      of eyes and >240 microm in 35% of eyes. In all eyes, foveal contour was abnormal,
      with foveal depression either absent (n = 7 [35%]) or shallow (n = 13 [65%]).
      Preservation of multiple inner retinal layers within the fovea was seen in 14
      eyes (70%). Vitreomacular traction or subretinal fluid was not seen in any eye.
      CONCLUSIONS: Anomalies in foveal anatomy by OCT may be a vestige of prematurity,
      appear to be independent of prior retinopexy, and can still be associated with
      excellent visual acuity.

PMID- 18046229
TI  - Foveal thickness and macular volume in patients with oculocutaneous albinism.
AB  - PURPOSE: To measure foveal thickness and macular volume in patients with
      oculocutaneous albinism (OCA) using optical coherence tomography (OCT) technology
      and to evaluate the possible association between albinism type and OCT retinal
      findings. METHODOLOGY: The authors measured retinal structures such as foveal
      thickness and macular volume of patients and obligate carriers of the various
      types of OCA using OCT technology. RESULTS: Participants with OCA (all types
      included) have thicker foveas (P = 0.0009) and less macular volume (P = 0.0022)
      than the general population. Carriers of mutations leading to OCA (all types
      included) have normal foveal thicknesses and higher macular volumes (P = 0.0009)
      than the general population. Participants with Hermansky-Pudlak syndrome (HPS)
      Type 1 have thicker foveas but less macular volume (P = 0.0468) than the general
      population. CONCLUSIONS: Results of this study suggest that patients with OCA
      (all types included) and patients with HPS-1 have thicker foveas than the general
      population. This may be due to the absence of foveal pit as part of foveal
      hypoplasia associated with OCA. Conversely, participants have lower macular
      volumes than the general population. This finding is compatible with loss of
      retinal nuclear layers in patients with OCA.

PMID- 18046230
TI  - Modified external needle drainage of subretinal fluid in primary rhegmatogenous
      retinal detachment: a prospective, consecutive, interventional, single-surgeon
      study.
AB  - PURPOSE: We describe surgical outcomes in a single-surgeon, consecutive series of
      patients who received scleral buckle placement for primary retinal detachment
      using a modified external needle drainage technique. METHODS: Eighty-two eyes of
      80 patients with primary retinal detachment underwent scleral buckle placement
      with modified external needle drainage. Preoperative, postoperative, and surgical
      data were collected. Regression analysis was used to evaluate the association
      between preoperative clinical data and number of surgeries. RESULTS: The retinal
      detachment most commonly involved 41% to 50% of the retina. Seventy-six eyes
      (92.7%) were repaired after 1 surgical procedure, 98.8%, after 2 procedures, and
      100%, after 3 procedures. No preoperative clinical variables were found to be
      significantly correlated with the number of surgeries performed. Vision improved
      an average of 0.3 logarithm of the minimal angle of resolution or 3 lines of
      vision (P < 0.001). One eye (1.2%) developed a localized subretinal hemorrhage at
      the drainage site that resolved spontaneously. CONCLUSIONS: The modified external
      needle drainage technique used during scleral buckle placement appears to be safe
      and effective in patients with primary retinal detachment.

PMID- 18046232
TI  - Outcomes of macular hole surgery in patients treated intraoperatively for retinal
      breaks and/or lattice degeneration.
AB  - PURPOSE: To assess the outcome of macular hole surgery in patients treated
      intraoperatively for retinal breaks and/or lattice degeneration. METHODS:
      Retrospective review of patients who underwent macular hole surgery from
      September 1998 to August 2005. Outcomes in eyes that received intraoperative
      endolaser photocoagulation for retinal breaks and/or lattice degeneration were
      compared to outcomes in a case-matched control group without retinal breaks or
      lattice degeneration. RESULTS: A total of 235 consecutive macular hole surgery
      cases were reviewed. Twenty-four eyes from 24 patients received intraoperative
      endolaser photocoagulation for retinal breaks and/or lattice degeneration.
      Macular hole closure occurred in all case and control eyes without any incidence
      of postoperative retinal detachment. Best-corrected visual acuity improvement of
      at least three Snellen lines occurred in 100% of case eyes and 92% of control
      eyes. CONCLUSION: Outcomes of macular hole surgery in patients with retinal
      breaks and/or lattice degeneration are similar to outcomes in the overall
      population when these conditions are treated with intraoperative endolaser
      photocoagulation. Postoperative retinal detachment does not appear to be
      correlated with treated retinal tears and greater attention should focus on
      detecting and managing intraoperative breaks. In our hands, routine use panoramic
      viewing has replaced indirect ophthalmoscopy, by saving time, and reducing the
      risk of contamination.

PMID- 18046231
TI  - Fluorescein and indocyanine green angiographies in Susac syndrome.
AB  - PURPOSE: Susac syndrome is a rare microangiopathy of the brain, retina, and
      cochlea that mainly affects young women. We studied the management of this
      disease using retinal fluorescein and indocyanine green angiographies. METHODS:
      Retrospective, observational case series of seven patients with Susac syndrome
      identified in ophthalmology and internal medicine departments. We reviewed
      medical, ophthalmologic, and angiographic records at study enrollment and during
      long-term treatment. Mean follow-up was 37 months. Best-corrected visual acuity,
      intraocular inflammation score, ophthalmoscopy data, automated perimetry score,
      and fluorescein and indocyanine green angiographic features were analyzed with
      the results of cerebral magnetic resonance imaging and spinal fluid analysis and
      ENT signs. RESULTS: Retinal fluorescein angiography showed focal nonperfused
      retinal arterioles with hyperfluorescent walls in all cases. Indocyanine green
      angiography showed normal choroidal circulation. Retinal vasculitis was
      uncontrolled in a patient treated with steroids. Improvement of retinal arteriole
      perfusion occurred during immunosuppressive treatment with cyclophosphamide.
      CONCLUSION: Absence of intraocular inflammation and focal, labile nonperfused
      retinal arterioles with integrity of choroidal circulation are monomorphic
      ophthalmologic features that could immediately suggest the diagnosis of Susac
      syndrome. Early ophthalmologic examination aided by retinal fluorescein
      angiography could be useful for managing cases of unexplained neurologic symptoms
      in women.

PMID- 18046233
TI  - Long-term outcomes of macular hole surgery with triamcinolone acetonide-assisted
      internal limiting membrane peeling.
AB  - PURPOSE: To report long-term anatomical and functional results after pars plana
      vitrectomy with internal limiting membrane (ILM) peeling using triamcinolone
      acetonide (TA) for idiopathic macular holes. DESIGN: Prospective, consecutive,
      interventional case series. METHODS: Ninety-six eyes of 94 patients who underwent
      macular hole surgery with TA-assisted ILM peeling were included in the study.
      Patients with <12 months of follow-up were excluded. On 82 phakic eyes,
      simultaneous phacoemulsification with intraocular lens implantation was
      performed. Follow-up examinations included clinical examination, determination of
      best-corrected visual acuity, intraocular pressure measurement, optical coherence
      tomography, Goldmann perimetry, and static perimetry using the Humphrey visual
      field analyzer. The main outcome measures were postoperative visual acuity,
      macular hole status, and postoperative complications. RESULTS: The mean follow-up
      period was 17 months (range, 12-30 months). TA improved visualization of the ILM,
      and the peeled area was seen as an area lacking white specks. All macular holes
      successfully closed after primary surgery. Mean visual acuity improved from 0.26
      to 1.0 at the final visit (P < 0.0001), with 90 eyes (94%) having improvement of
      visual acuity. Postoperative complications included retinal detachment in one
      patient and transient intraocular pressure elevation in five patients.
      CONCLUSIONS: Although transient intraocular pressure elevation was observed in a
      few patients, the use of TA in macular hole surgery may be an effective and safe
      technique to facilitate visualization of the ILM and can lead to good long-term
      anatomical and functional results.

PMID- 18046234
TI  - Quantification of sedimented triamcinolone for intravitreal injection.
AB  - PURPOSE: To develop a practical method to concentrate triamcinolone acetonide for
      intravitreal injection. METHODS: A protocol using sedimentation was developed to
      increase the concentration of triamcinolone acetonide in a 0.1 mL dose. Two
      variables were investigated: sedimentation time and initial volume of
      triamcinolone acetonide. Predetermined volumes (0.2 mL to 1 mL) of triamcinolone
      acetonide were aspirated into tuberculin syringes. Each syringe was placed in a
      vertical position for a designated time (0 to 120 minutes). The supernatant was
      then discarded to reduce the volume to 0.1 mL. High-performance liquid
      chromatography was then used for quantification of the triamcinolone acetonide.
      RESULTS: The greatest concentrations of triamcinolone acetonide were seen after
      120 minutes of sedimentation. At that time point, the 0.2 mL, 0.3 mL, and 0.5 mL
      initial volumes resulted in, respectively, 7.4 mg +/- 0.8 mg (mean +/- SE), 9.8
      mg +/- 0.2 mg, and 16.4 mg +/- 0.7 mg triamcinolone acetonide in 0.1 mL. The 1.0
      mL initial volume resulted in 25.7 mg +/- 0.9 mg triamcinolone acetonide in 0.1
      mL; this was the maximum concentration achieved in the experiment. CONCLUSION:
      The authors have developed a simple protocol to use sedimentation to greatly
      increase the concentration of triamcinolone acetonide, starting from commercially
      available triamcinolone acetonide up to a maximum of 25.7 mg per 0.1 mL (257 +/-
      9 mg/mL). This study demonstrates a practical and quantifiable method to increase
      triamcinolone concentration for intravitreal injections.

PMID- 18046235
TI  - Pharmacokinetics and retinal distribution of ranibizumab, a humanized antibody
      fragment directed against VEGF-A, following intravitreal administration in
      rabbits.
AB  - PURPOSE: Ranibizumab (Lucentis) is a humanized antigen-binding fragment designed
      to inhibit all isoforms and active degradation products of vascular endothelial
      growth factor A (VEGF-A); it is in clinical development for the treatment of
      neovascular age-related macular degeneration (AMD). This study evaluated its
      pharmacokinetics (PK) and retinal distribution in rabbits when administered
      intravitreally (ITV). METHODS: A total of 27 New Zealand white rabbits received a
      single bilateral ITV injection of ranibizumab 625 muicrog/eye (Group 1, n = 24)
      or I-labeled ranibizumab 625 microg/eye, 22.5 microCi/eye (Group 2, n = 3).
      Ranibizumab concentration was determined in the vitreous, aqueous humor, and
      serum up to 60 days postdose by enzyme-linked immunosorbent assay in Group 1.
      Group 2 eyes were microautoradiographed on days 1-4. RESULTS: Ranibizumab has a
      terminal half-life of 2.9 days in the ocular compartments. Systemic exposure was
      low, measuring less than 0.01% of vitreous exposure when comparing AUC0-t values.
      Microautoradiography analysis demonstrated that ranibizumab penetrated all
      retinal layers, reaching the choriocapillaris on days 1, 2, and 4. CONCLUSIONS:
      This study demonstrates that following ITV injection, ranibizumab has a vitreous
      half-life of 2.9 days with minimal systemic exposure. Ranibizumab rapidly
      penetrates through the retina to reach the choroid, supporting its clinical
      development for neovascular AMD.

PMID- 18046236
TI  - Scanning laser polarimetry demonstration of retinal nerve fiber layer damage in
      human immunodeficiency virus-positive patients without infectious retinitis.
AB  - BACKGROUND: To use scanning laser polarimetry with variable corneal compensation
      to measure the retinal nerve fiber layer (RNFL) in human immunodeficiency virus
      (HIV)-infected patients. METHODS: Three groups were analyzed in a prospective
      cohort study from one center. Group A consisted of 52 eyes of HIV-positive
      patients whose CD4 cell counts had never fallen below 100/mm (1.0 x 10/L). Group
      B included 60 eyes of HIV-positive patients with CD4 cell counts that had fallen
      below 100/mm for at least 6 months in their history. Group C consisted of 50 eyes
      of HIV-negative patients. None of the eyes had a history of infectious retinitis.
      Retinal birefringence imaging studies were performed using a commercially
      available scanning laser. Superior, inferior, and ellipse averages as well as
      nerve fiber indicator parameters were used for comparison. RESULTS: Group B
      significantly differed from group C in all parameters. Group B also differed from
      group A in all parameters with the exception of superior average. No difference
      was detected between group A and group C. CONCLUSION: Scanning laser polarimetry
      demonstrated RNFL thinning in HIV-positive patients without retinitis who had a
      history of low CD4 cell counts compared with HIV-positive subjects with high CD4
      cell counts and HIV-negative patients.

PMID- 18046237
TI  - Outcome of diabetic vitrectomy in Latino population.
AB  - PURPOSE: Evaluation of visual acuity and anatomic outcome in Latino patients
      undergoing vitrectomy for proliferative diabetic retinopathy, using silicone oil
      or gas tamponade. METHODS: Retrospective review of 57 vitrectomies, 42 in Latino
      patients, performed by a single surgeon over a 3-year period. RESULTS: Seventy
      four percent of vitrectomies were on patients of Latino descent. Sixty-three
      percent of eyes had traction retinal detachments involving the macula. Overall,
      29% in the Latino group received silicone oil tamponade, while the remainder
      received gas tamponade. In the gas treatment group, 16% developed rhegmatogenous
      detachments, while no rhegmatogenous detachments occurred in oil-treated eyes.
      This difference was not statistically significant. Follow-up ranged from 1 to 4
      years (median, 1 year). The change from pre- to postsurgery visual acuity was
      calculated for both gas and oil treated groups, showing no statistically
      significant difference. Pre- and postsurgery visual acuity median was hand
      motions for both. CONCLUSION: There was no statistically significant difference
      in final anatomic outcome or visual outcome in Latino eyes undergoing surgery for
      severe proliferative diabetic retinopathy. Silicone oil and gas tamponade
      appeared to work equally well in this population.

PMID- 18046238
TI  - Correlation of the extent and duration of rhegmatogenous retinal detachment with
      the expression of matrix metalloproteinases in the vitreous.
AB  - BACKGROUND: Investigation of the activity of matrix metalloproteinase (MMP)-2 and
      -9 and protein levels of MMP-1, -3, -8, and the tissue inhibitor of MMPs (TIMP)-1
      in the vitreous of patients with rhegmatogenous retinal detachment (RRD) and
      establishment of potential correlations of MMPs with clinical parameters.
      METHODS: Thirty-two vitreous samples from patients with RRD and 9 vitreous
      samples from human organ donors (controls) were assayed for MMP-1,-3, -8, and
      TIMP-1 levels using enzyme-linked immunosorbent assay and MMP-2 and -9 activity
      employing gelatin zymography. RESULTS: MMP-1, MMP-3, proMMP-2, proMMP-9, MMP-9,
      and TIMP-1 were higher in vitreous from patients with RRD as compared to organ
      donors. Overall, MMPs and TIMPs were differentially expressed in vitreous from
      RRD with respect to the duration and extent of RRD. Regression analysis for all
      data indicated that a model consisting of MMP-2 and TIMP-1 could estimate the
      extent of RRD. CONCLUSION: Levels of MMPs and TIMP-1 studied are elevated in
      vitreous during RRD. MMP-2 and TIMP-1 may have a more prominent and persistent
      role than other MMPs in the wound healing process of the retina during RRD. A
      regression model consisting of MMP-2 and TIMP-1 may prove to be of potential use
      in providing information for the evaluation of the extent of RRD.

PMID- 18046239
TI  - Safety profile of a taurine containing irrigation solution (AcriProTect) in pars
      plana vitrectomy.
AB  - PURPOSE: To evaluate the clinical safety of a taurine containing irrigation
      solution (AcriProTect) before its routine application in pars plana vitrectomy
      (PPV). METHODS: Twenty-five patients who underwent PPV were included in this
      prospective interventional clinical study. Standard irrigation solution
      containing the addendum 3 mmol/L taurine was used during PPV. Postoperative
      follow-up visits included a standard eye examination, corneal thickness
      measurements, endothelial cell counts, determination of the foveal thickness by
      optical coherence tomography (OCT), and an electrophysiologic examination. For
      statistical analysis Wilcoxon test was used. RESULTS: Significant improvement of
      visual acuity (VA) was observed at the 3- and 6-month controls (P = 0.024; P =
      0.002 for 3 and 6 months, respectively). Endothelial cell counts and corneal
      thickness at 3 and 6 months were not significantly different from preoperative
      values (P = 0.204; P = 0.126 for endothelial cell count and P = 0.475; P = 0.095
      for corneal thickness at 3 and 6 months, respectively). Both scotopic and
      photopic Ganzfeld electroretinography and electro-oculography did not show
      significant changes during the follow-up. No increase in complication rate was
      detected. CONCLUSIONS: The investigation demonstrates a good biocompatibility of
      taurine-containing irrigation solution developed for vitrectomy in humans
      concomitant with habitually observed good functional outcome.

PMID- 18046240
TI  - Comparison of comorbid conditions between neovascular age-related macular
      degeneration patients and a control cohort in the medicare population.
AB  - PURPOSE: To determine whether comorbidities are more prevalent among individuals
      with neovascular age-related macular degeneration (NV-AMD) than individuals
      without AMD. METHODS: This 2-year, retrospective, case-control study included
      Medicare beneficiaries (standard 5% analytic sample) continuously enrolled from
      January 1, 2003, to December 31, 2004, excluding those in managed care plans. The
      NV-AMD cohort included individuals >or=65 at baseline with a diagnosis of NV-AMD
      in 2003 and 2004. Age-, gender-, and race-matched controls were selected from
      those with no AMD. Comparisons were made for 13 general categories of non-eye
      related diseases and 18 specific comorbidities based on ICD-9-CM codes. Two-year
      prevalence was calculated by condition and cohort; odds ratios and 99% confidence
      intervals were calculated (logistic regression). RESULTS: Analyses included
      26,057 subjects and an equal number of controls. Nearly all subjects had at least
      one comorbidity, and >80% in each cohort had five or more comorbidities across
      general disease categories. Prevalence of 7/13 general disease categories
      exceeded 50% in both cohorts; rates for 12/13 categories were significantly
      higher in those with NV-AMD (P < 0.001). Prevalence of 13/14 non-eye-related and
      4/4 eye-related specific comorbidities was significantly higher among NV-AMD
      subjects (P < 0.05). A more than 20% greater odds for NV-AMD subjects was noted
      for hypertension, hypercholesterolemia, emphysema, chronic obstructive pulmonary
      disease, atherosclerosis, arthritis, coronary heart disease, cataract, glaucoma,
      and myopia. CONCLUSION: Patients with NV-AMD are significantly more likely to
      have comorbidities, many of which could be life-threatening.

PMID- 18046241
TI  - Silicone oil removal in pseudophakic and aphakic eyes.

PMID- 18046242
TI  - 27-gauge transconjunctival nonvitrectomizing vitreous surgery for epiretinal
      membrane removal.

PMID- 18046243
TI  - Diagnostic and therapeutic challenges.

PMID- 18046244
TI  - Chronic lymphocytic leukemia masquerading as uveitis.

PMID- 18046245
TI  - Optical coherence tomography of progressive outer retinal necrosis.

PMID- 18046247
TI  - Oxygen solubility in water is highly dependent on temperature.

PMID- 18046248
TI  - Optical coherence tomography (OCT) features of fibrovascular pigment epithelial
      detachment (PED).

PMID- 18046250
TI  - Long-term observation of fundus infrared fluorescence after indocyanine green
      (ICG)-assisted vitrectomy.

PMID- 18046251
TI  - Oxygenation of intraocular irrigation fluids with an in-line oxygenation system.

PMID- 18046254
TI  - Six cases of eccentric macular holes after vitrectomy with peeling of epimacular
      proliferation.

PMID- 18046256
TI  - Bilateral congenital cholesteatoma.

PMID- 18046257
TI  - Magnetic resonance imaging and neuropsychological testing after middle fossa
      vestibular schwannoma surgery.
AB  - OBJECTIVE: To analyze temporal lobe gliosis and temporal lobe dysfunction after
      middle fossa vestibular schwannoma surgery. STUDY DESIGN: Temporal lobe analysis
      of a series of cases. SETTING: Tertiary referral center. PATIENTS: Thirty-two
      patients after enlarged middle fossa surgery (EMFS) and 20 subjects for control
      (preferably husbands/wives). INTERVENTIONS: Magnetic resonance evaluation of the
      temporal lobe and neuropsychological testing. MAIN OUTCOME MEASURES: Magnetic
      resonance imaging of the temporal lobe 1 year after treatment and
      neuropsychological testing (Berliner Amnesia Test [BAT], Boston Naming Test [BT],
      Token Test, Beck Depression Inventory, Freiburger Personality Inventory).
      RESULTS: Temporal lobe gliosis after EMFS was observed in 22 of 32 analyzed
      patients (degree of gliosis: 11, slight; 9, moderate; 2, severe).
      Neuropsychological testing of 23 of the 32 previously analyzed patients after
      EMFS compared with control subjects (n=20) found only in few subdomains (figural
      score, personality test) statistically significant worse test results, but no
      major disturbances of the temporal lobe function compared with the control group.
      Only one patient with a finding of severe temporal lobe gliosis was proven in the
      BAT and BT to have a temporal lobe deficit. CONCLUSION: In a significant number
      of patients, temporal lobe gliosis has to be expected after EMFS; however, the
      gliosis is only slight or moderate in most of the patients and not associated
      with essential functional deficits of the temporal lobe. Nevertheless, the
      possibility of a severe temporal lobe gliosis with functional deficits in the BAT
      and BT has to be taken into consideration.

PMID- 18046258
TI  - Familial clustering of migraine, episodic vertigo, and Meniere's disease.
AB  - OBJECTIVE: To evaluate the association between migraine, episodic vertigo, and
      Meniere's disease in families. STUDY DESIGN: Clinical report. SETTING: University
      Neurotology Clinic. PATIENTS: Index patients identified with Meniere's disease
      and migraine and their family members. INTERVENTION: Structured interview to
      assess a diagnosis of migraine, episodic vertigo, and Meniere's disease in 6
      families. Genotyping was performed on 3 sets of twins to analyze monozygosity or
      dizygosity. MAIN OUTCOME MEASURES: Clinical history of migraine, episodic
      vertigo, and Meniere's disease. RESULTS: Six index patients and 57 family members
      were interviewed either by a senior neurologist in person or over the phone by a
      trained study coordinator. An additional 6 family members completed
      questionnaires by mail. All 6 index patients had Meniere's disease and migraine.
      Twenty-six (41%) of the 63 relatives met International Classification of Headache
      Disorders II criteria for migraine headaches. Thirteen (50%) of these 26
      experienced migraine with aura. Three others experienced typical aura without
      headache. Seventeen (27%) of 63 family members experienced recurrent spells of
      spontaneous episodic vertigo. There was one twin pair in each of 3 families; 2
      pairs were monozygotic and one was dizygotic. In each twin pair, one twin had
      migraine and Meniere's disease, whereas the other experienced migraine and
      episodic vertigo without auditory symptoms. CONCLUSION: The frequent association
      of episodic vertigo, migraine, and Meniere's disease in closely related
      individuals, including identical twins supports the heritability of a migraine
      Meniere's syndrome, with variable expression of the individual features of
      hearing loss, episodic vertigo, and migraine headaches.

PMID- 18046259
TI  - Are stage IV vestibular schwannomas preoperatively different from other stages?
AB  - OBJECTIVE: The aim of this study was to focus on the clinical and paraclinical
      symptoms of patients suffering from Stage IV vestibular schwannomas (VSs).
      PATIENTS: In this prospective study, we included 734 patients who have VS and
      candidates for operation. MAIN OUTCOME MEASURES: Patients were classified as
      having Stage I, II, III, or IV tumors according to Tos criteria as evaluated by
      magnetic resonance imaging. PREOPERATIVE CLINICAL EVALUATION: We recorded the
      occurrence of complaints (%) and duration (yr) of hearing loss, tinnitus, and
      balance disorder. Preoperative paraclinical evaluation included pure-tone (PTA)
      and speech audiometry, auditory brainstem response (ABR) patterns, and vestibular
      deficit at videonystamography (VNG). Continuous variables were compared between
      Stage IV and other stages using analysis of variance. Qualitative variables
      expressed as a percentage of presence were compared between Stage IV and other
      stages using percentage comparison. RESULTS: Quantitative Parameters. Patients
      with Stage IV VS were significantly younger as compared with patients with other
      stages. Stage IV hearing loss was greater compared with other stages at 250 and
      500 Hz but smaller at 2,000 and 8,000 Hz. We found no difference in the loss of
      PTA between Stage IV and the other stages. Speech discriminancy score was smaller
      in Stage IV. The durations of hearing loss, tinnitus, and balance disorders were
      similar whatever the tumor stage. Auditory brainstem response patterns showed no
      difference in Wave III latency between Stage IV VS and other stages, whereas Wave
      V latency and V-I interval were higher in Stage IV. Both ABR threshold and VNG
      caloric deficit were higher in Stage IV VS compared with other stages.
      Qualitative Parameters. The percentage of patients with Stage IV was lower than
      that with Stages II and III. The percentage of men and women was similar in all
      stages. The occurrence of hearing loss was similar in all stages, whereas that of
      tinnitus was lower in Stage IV compared with Stages I and II. In contrast, the
      occurrence of balance disorder was higher in Stage IV compared with all other
      stages. CONCLUSION: In clinical and paraclinical manifestation, Stage IV VS is
      different from the other stages. The PTA differences may be attributed to the
      younger age. Occurrence of clinical symptoms, ABR, and VNG pattern can be
      explained by the fact that Stage IV develops rapidly in the vestibular, rather
      than the cochlear nerve and by the fact that larger tumors can be cerebellar
      compression. This has been confirmed by the higher occurrence of balance
      disorders in Stage IV and the lower occurrence of tinnitus with similar hearing
      loss in all stages.

PMID- 18046260
TI  - The cost and analysis of nonuse of cochlear implants.
AB  - OBJECTIVE: Analysis of the cost implications and reasons for nonuse of cochlear
      implants in an established cochlear implant unit. STUDY DESIGN: Clinical data
      were analyzed retrospectively to construct a table of cochlear implant use over
      time to identify nonuse and to suggest the reasons for this. SETTING: Yorkshire
      Cochlear Implant Service is a tertiary referral center. PATIENTS: Three hundred
      forty consecutively implanted patients from 1990 to 2005. MAIN OUTCOME MEASURES:
      Life table analysis showed that most children used their implant (p = 0.7 during
      11 yr). However, 11 of 155 children and 2 of 185 adults became nonusers during
      the period of study. The 11 children stopped because of age at implant,
      educational placement, and family support. Two adults stopped because of
      psychological issues and inability to adapt to the signal. Surgical and implant
      costs have initial impact, with subsequent years' costs reflecting programming
      issues and maintenance. When considering nonuse, there are 2 effects: first, no
      more costs are incurred, and second, no more years of use are accumulated. Thus,
      nonuse reduces both costs and years. Costs of gaining a year of use as a function
      of time showed that there was little financial impact from the 11 children
      nonusers. As a ratio of "no nonuse" and observed "nonuse" in children, the ratio
      is 1.07 by 13 years of implantation (7%). The adult group was too few to analyze.
      CONCLUSION: The nonuse added 7% to the average cost. Retrospective audit
      identifies that patient selection by a multidisciplinary team is crucial to
      reducing nonuse.

PMID- 18046261
TI  - Chronic suppurative otitis media, caloric testing, and rotational chair testing.
AB  - OBJECTIVE: To determine the incidence of caloric and rotational chair testing
      (ROT) abnormalities in a group of patients with chronic suppurative otitis media
      (CSOM) and to correlate caloric test results with ROT. PATIENTS: Twenty-five
      patients with CSOM with or without cholesteatoma who were to undergo
      tympanomastoid surgery. INTERVENTIONS: Caloric and ROT. MAIN OUTCOME MEASURES:
      History of dizziness. Vestibular test abnormalities defined by caloric weakness
      (CW), reduced gain, abnormal phase, or asymmetry on ROT. RESULTS: Among the 25
      patients, 13 had bilateral CSOM-most with long-standing disease and history of
      previous surgical intervention. Of the 25 patients, 19 (76%) demonstrated either
      unilateral or bilateral CW. Eighteen (72%) demonstrated abnormalities on ROT.
      Eleven patients (44%) had complaints of vertigo/dizziness, although 2 of these
      patients had both normal caloric testing and ROT. Unilateral or bilateral CW was
      80% accurate in predicting an ROT abnormality, whereas the symptom of
      vertigo/dizziness was only 48% accurate in predicting an ROT abnormality.
      CONCLUSION: The incidence of CW among CSOM patients in this study was high and
      correlated well with abnormalities on ROT. Interestingly, ROT results correlated
      better with CW than symptoms of dizziness/vertigo. Although CW findings can be
      the result of technical limitations in testing patients with CSOM, ROT
      corroboration of these results suggest that they are valid findings.

PMID- 18046262
TI  - Titanium CliP piston versus platinum-ribbon Teflon piston: piston and fenestra
      size affect air-bone gap.
AB  - OBJECTIVE: To analyze if titanium material and a clip attachment to the incus
      offer a hearing result advantage over the traditional Teflon piston in stapes
      surgery. STUDY DESIGN: Retrospective chart review. SETTING: Subspecialty private
      practice. PATIENTS: One hundred seven ears in 97 consecutive patients who had
      primary stapes surgery during 2003 to 2005. INTERVENTION: The first 74 ears
      received either a Teflon 0.5- or 0.6-mm piston, and the last 33 received a
      titanium 0.6-mm piston. MAIN OUTCOME MEASURES: American Academy of Otolaryngology
      Head and Neck Surgery guidelines, including 4-frequency pure-tone average air
      bone gap and success rate (gap, 10 dB). RESULTS: Mean pure-tone average air-bone
      gap for the Teflon 0.6-mm piston (5.1 dB) was significantly smaller than for the
      titanium 0.6-mm piston (8.1 dB) and the Teflon 0.5-mm piston (7.5 dB). Success
      rate did not differ. Although labeled as 0.6-mm pistons, the Teflon piston
      diameter was 10% greater than the titanium piston. Results were comparable among
      devices when adjusted for true piston diameter. Results for the titanium piston
      were significantly better when the fenestra was no more than 0.05 mm larger than
      the piston diameter. CONCLUSION: Comparing 2 pistons designated 0.6 mm in
      diameter, the Teflon piston produced better hearing results than the titanium
      device. However, actual piston diameter differed between devices that contributed
      to the superior results with the larger Teflon piston. In addition, the titanium
      piston performed better with a small stapes fenestra diameter that suggests an
      advantage for titanium over Teflon in certain conditions. The clip design was
      problematic for a few patients.

PMID- 18046264
TI  - Providers' perceived barriers to sexually transmitted disease care in 2 large
      health maintenance organizations.
AB  - GOAL: To identify providers' perceived barriers to sexually transmitted disease
      (STD) care in 2 health plans and plan-, clinician-, and patient-level factors
      that were associated with these barriers in order to inform quality improvement
      interventions. STUDY DESIGN: Surveys were mailed to a stratified sample of 1000
      physicians, physician assistants, and nurse practitioners at 2 large health plans
      in 1999-2000. Of the 743 (82%) providers who received questionnaires and
      responded, data were analyzed from 699 with complete specialty information.
      RESULTS: Ninety-five percent of providers identified at least 1 barrier to STD
      care. The most commonly cited barriers in both plans related to insufficient time
      and staff to address STDs, to counsel patients or manage sex partners, to keep
      current with managing high-risk patients, and to monitor patient adherence to
      recommendations to abstain from sex or use condoms during treatment. Nurse
      practitioners and specialists in obstetrics and gynecology were more likely to
      cite these barriers. Providers in staff models were more likely to cite the most
      common patient-level barriers. Few cited barriers related to diagnostic and
      treatment services. CONCLUSIONS: Interventions in health plans are necessary to
      address constraints related to time and staff performing STD related care,
      keeping current with managing high-risk patients, and supporting patient
      adherence to provider recommendations.

PMID- 18046265
TI  - Prevalence of human immunodeficiency virus, Chlamydia trachomatis, and Neisseria
      gonorrhoeae and risk factors for sexually transmitted infections among immigrant
      female sex workers in Catalonia, Spain.
AB  - OBJECTIVES: To determine the prevalence of human immunodeficiency virus (HIV),
      Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) among immigrant female
      sex workers (FSW) according to their geographic area of origin and identify
      possible risk factors independently associated with current infection with CT
      and/or NG. STUDY DESIGN: Cross-sectional study of 357 FSW in Catalonia in 2005.
      Information on sociodemographic and sex work characteristics, use of alcohol and
      drugs, sexual practices, and the use of social and health care services was
      collected. Oral fluid and urine samples were collected to determine the
      prevalence of HIV and CT/NG, respectively. Factors independently associated with
      CT/NG were assessed using multivariate logistic regression models. RESULTS: A
      total of 36.4% of women were from Eastern Europe, 34.5% from Latin America, and
      29.1% from Africa. Overall CT and NG prevalence were 5.9% [95% confidence
      interval (CI): 3.7-8.9] and 0.6% (95% CI: 0.1-2.0), respectively. No differences
      were observed by geographic origin. Three African women were HIV positive
      (overall HIV prevalence was 0.8%, 95% CI: 0.2-2.4). In multivariate analysis,
      younger age and unprotected sex with clients were associated with the presence of
      CT/NG. CONCLUSIONS: The prevalence of sexually transmitted infections among FSW
      in Catalonia was lower than in other European countries. Even though the
      prevalence of HIV was only 0.8%, it could increase in the future given the high
      vulnerability of these women and their wide geographic mobility. It is necessary
      to continue with the work carried out by nongovernmental organizations (harm
      reduction programs, outreach programs, and safe sex workshops) as well as to
      facilitate the access to health centers, especially for the youngest women.

PMID- 18046266
TI  - [Congenital grouped albinotic spots: a case report].
AB  - INTRODUCTION: Case report of congenital grouped albinotic spots. OBSERVATION: A
      24-year-old woman was referred for frontal headache related to +1.50
      hypermetropia. Visual acuity was 20/20 in both eyes. During routine examination,
      fundus examination revealed multiple, irregular white spots involving the
      juxtapapillary and peripheral retina in both eyes. Color vision, visual fields,
      and electroretinographic findings were normal. Fluorescein angiograms showed
      hyperfluorescent spots; indocyanine green (ICG) showed hypofluorescence of these
      lesions. CONCLUSION: These albinotic spots are uncommon benign developmental
      lesions of the retinal pigment epithelium; they appear to represent focal
      thickening of the retinal pigment epithelium (RPE) that is filled with white
      material, possibly an abnormal precursor of melanin.

PMID- 18046263
TI  - High-risk sexual and drug using behaviors among male injection drug users who
      have sex with men in 2 Mexico-US border cities.
AB  - OBJECTIVES: The population of Latino men who have sex with men (MSM) and who are
      also injection drug users (IDUs) is understudied. We explored risk behaviors of
      MSM/IDUs compared with other male IDUs in 2 Mexican border cities. STUDY DESIGN:
      In 2005, IDUs who had injected within the previous 30 days were recruited using
      respondent-driven sampling (RDS) in Tijuana and Ciudad Juarez. They underwent
      antibody testing for HIV, HCV, and syphilis and interviewer-administered surveys.
      Men were categorized as MSM if they reported > or =1 lifetime male partners.
      Logistic regression was used to compare MSM/IDUs with non-MSM/IDUs. RESULTS: A
      third (31%) of 377 male IDUs were categorized as MSM (47% in Tijuana and 13% in
      Ciudad Juarez, P <0.01). Combined RDS-adjusted prevalence of HIV and Hepatitis C
      was 3% (95% CI: 1, 5) and 96%, (95% CI: 94, 99) respectively, while 17% (95% CI:
      2, 36) of MSM and 8% (95% CI: 3, 12) of non-MSM tested positive for syphilis
      antibody. In multivariate logistic regression adjusted for site, MSM/IDUs were
      more likely than non-MSM/IDUs to have ever used inhalants (OR: 3.4; 95% CI: 1.8,
      6.2) or oral tranquilizers (OR: 2.4; 95% CI: 1.3, 4.6), received treatment for a
      drug problem (OR:1.9; 95% CI: 1.1, 3.2) shared needles in the last six months
      (OR: 2.1; 95% CI: 1.0, 4.2) and also had higher numbers of lifetime female
      partners (log-transformed continuous variable, OR: 1.6; 95% CI: 1.2, 2.1).
      CONCLUSIONS: In these Mexican cities, the proportion of MSM among male IDUs was
      high. Compared with other male IDUs, MSM/IDUs were more likely to engage in
      behaviors placing them at risk of acquiring HIV/STIs. Culturally appropriate
      interventions targeting Latino MSM/IDUs are warranted.

PMID- 18046267
TI  - [A large intraocular foreign body].
AB  - INTRODUCTION: Penetrating wounds to the eyeball with penetration of a foreign
      body at the posterior segment are often extremely serious for the eye. The
      equipment available to extract them can sometimes be inadequate. OBSERVATION: We
      report the case of a 38-year-old man hospitalized for a penetrating wound of the
      eyeball with a voluminous foreign body incarcerated in the retina. Because of the
      size of the foreign body it could not be extracted with the usual forceps. We
      describe the assembly put together during the intervention using an intramuscular
      needle and 7/0 virgin silk that allowed its extraction. CONCLUSION: This lasso
      provides a very effective, easy and nontraumatic grasp of voluminous foreign
      bodies in the vitreal cavity.

PMID- 18046268
TI  - [Orbital metastasis of liposarcoma].
AB  - INTRODUCTION: Liposarcoma, the most common soft tissue sarcoma in adults, rarely
      involves the orbit. Primary orbital liposarcomas are extremely rare, with less
      than 30 cases previously reported. Metastatic orbital liposarcomas are also
      extremely rare, with only a few cases documented in the literature. We report a
      new case of an orbital metastatic liposarcoma and review the literature.
      OBSERVATION: A 57-year-old man with a history 5 years before of myxoid
      liposarcoma on the right calf, completely surgically resected, was admitted for
      recent proptosis of the left eye. A computed tomographic scan revealed a
      heterogeneously enhancing, left orbital mass measuring 30x23x20 mm. The mass
      adhered to the internal medial muscle without extension to the optic nerve. A
      biopsy was taken, which showed typical aspects of myxoid liposarcoma. The patient
      underwent an orbital left exenteration after first refusing any proposed
      treatment. CONCLUSION: Liposarcoma metastatic to the orbit is exceptional. It
      should be suspected in a patient with exophthalmia caused by a space-occupying
      lesion and a history of liposarcoma.

PMID- 18046269
TI  - [Bilateral optic atrophy in a drug addict].
AB  - Bilateral optic neuropathy in a young man is suggestive of hereditary or toxic
      damage. We describe the case of a 38-year-old man with bilateral optic
      neuropathy. His best corrected visual acuity was light perception OD and 20/125
      OS. The patient's history revealed an addiction to heroin. Three drugs - heroin,
      quinine, and cocaine - were considered as a possible cause, which is discussed
      further. We suggest that the condition reported here may be attributed to the use
      of heroin. This underlines the importance of meticulous history taking in
      diagnosing a young man with bilateral loss of vision.

PMID- 18046271
TI  - [Serious corneal complication after ptosis surgery: six case reports].
AB  - PURPOSE: To assess the occurrence of serious corneal complications in ptosis
      surgery and identify their determining factors. PATIENTS AND METHODS:
      Retrospective study conducted on 3,500 patients over 20 years. All the clinical
      and etiological types of ptosis were treated in compliance with operative
      contraindications. All four techniques of ptosis surgery were performed (anterior
      levator resection, the anterior levator aponeurotic approach, Muller's muscle
      shortening, and brow suspension). Data regarding serious corneal complications
      were collected using hospital patient records. RESULTS: Six serious corneal
      complications were noted in four males and two females. Evisceration was
      necessary in two cases and prolonged hospital care in four cases, requiring
      occasional medial tarsorrhaphy surgery. Complications were observed in malformed
      congenital ptosis associated with an oculomotor disorder and in one case of
      congenital III paralysis. Young age seems to be a particular risk. Corneal
      complications can occur long after initial surgery. Predisposing factors were
      noted such as an associated oculomotor disorder, blepharoconjunctivitis, severe
      eye dryness, and specific working environments. CONCLUSION: Serious corneal
      complications in ptosis surgery are rare. However, a risk may occur long after
      initial surgery. Congenital malformation ptosis associated with oculomotor
      disorder seems to present a higher risk of corneal complication in combination
      with specific predisposing factors.

PMID- 18046270
TI  - [Craniofacial approach for orbital tumors and ultrasonic bone cutting].
AB  - BACKGROUND: Removal of orbital tumors is a difficult problem. The goal of this
      study was to evaluate the advantages of the craniofacial approach to remove such
      tumors and to evaluate ultrasonic bone cutting during the procedure. METHOD: The
      authors reviewed their experience with 57 tumors of the posterior cavity using
      lateral craniofacial and frontal transsinus approaches. Orbital osteotomies were
      performed with mechanical instruments or piezoelectric bone surgery as a
      minimally invasive surgery. For each case, the quality of bone cutting and soft
      tissue damage were evaluated. RESULTS: Craniofacial approaches are simple and
      fast. Under the microscope, they provide a good view of the entire posterior
      orbital cavity. Using Piezosurgery, the functional results are good with no soft
      tissue damage. These advantages balance with the increased operative time
      required by ultrasonic bone cutting. CONCLUSION: This study shows the advantages
      of craniofacial approaches for removal of posterior orbital tumor. Moreover, the
      present preliminary report introduces and demonstrates the utility of
      piezoelectric bone surgery in craniofacial approaches for orbital tumors.

PMID- 18046272
TI  - [Unilateral keratoconus and mirror image in a pair of monozygotic twins].
AB  - We report the first observation to our knowledge of mirror unilateral keratoconus
      in monozygotic twins. The observation focuses on monozygotic twins, followed for
      5 years. The progression of the refraction, the clinical examination, the video
      topographic data, and the Orbscan elevation curves of the twins were collected
      and analyzed. For each twin, there was slightly progressive unilateral
      keratoconus during that time, located on the right for the first twin and on the
      left for the second one. Within the current limits of our diagnostic means, it
      appears to be the first case of mirror unilateral keratoconus in monozygotic
      twins. Several cases of mirror pathologies have been described, mainly concerning
      the renal and dental organs. The appearance of such mirror pathologies may be the
      consequence of the rise of a genetic or environmental factor during the
      acquisition of the symmetry of the zygote, occurring before its split into two
      monozygotic embryos.

PMID- 18046273
TI  - [Nd:Yag laser treatment of anterior capsule contraction syndrome after
      phacoemulsification].
AB  - INTRODUCTION: Anterior capsule contraction syndrome after phacoemulsification is
      rare and can compromise visual acuity. Nd:Yag laser capsulotomy is a good
      alternative in limited forms of contraction. OBSERVATIONS: We report four cases
      of anterior capsule contraction syndrome developed after a mean follow-up of 8
      months after phacoemulsification and acrylic intraocular lens implantation.
      Nd:Yag laser capsulotomy was performed to help resolve the contraction and its
      symptoms. No relapses occurred during the follow-up. CONCLUSION: Nd:Yag laser
      capsulotomy is effective and safe in managing limited forms of anterior capsule
      contraction syndrome after phacoemulsification. Surgery is an alternative to
      Nd:Yag capsulotomy in severe cases.

PMID- 18046274
TI  - [Phacoemulsification in eyes with white cataracts: results and complications].
AB  - PURPOSE: To compare visual acuity and complications in phacoemulsification in
      eyes with white cataract and in eyes with immature senile cataract. PATIENTS AND
      METHODS: This was a prospective study on 36 eyes in 34 patients with white
      cataract (group 1) and 36 eyes in 36 patients with immature senile cataract
      (group 2). RESULTS: In group 1, mean preoperative visual acuity was 1/100 and
      mean postoperative visual acuity was 5/10 at 1 month. Posterior capsule tears
      occurred in four eyes (11%). In group 2, mean preoperative visual acuity was 2/10
      and mean postoperative visual acuity was 7/10 at 1 month. No posterior capsule
      tear was observed. The preoperative visual acuity was significantly lower in
      group 1 (p=1.8x10(-14)). Postoperative visual acuities were not significantly
      different between the two groups (p=0.07). The increase in visual acuity was
      significantly higher in group 1 (p=2.2x10(-11)). DISCUSSION: Our study shows that
      white cataract is not a risk factor of poor postoperative visual acuity and the
      increase in visual acuity is greater in the white cataract group than in the
      immature cataract group. CONCLUSION: The results of phacoemulsification in white
      cataracts are satisfactory in spite of a high rate of posterior capsule rupture
      in our study.

PMID- 18046275
TI  - [Trypan blue capsule staining for phacoemulsification in white cataract].
AB  - OBJECTIVE: To study the results of phacoemulsification in eyes with white
      cataract using trypan blue for capsule staining. PATIENTS AND METHODS: Thirty
      patients who had white cataract were included in this prospective study. They had
      phacoemulsification and continuous curvilinear capsulorhexis using trypan blue.
      Intraoperative problems related to capsulorhexis and phacoemulsification as well
      as postoperative outcomes where analyzed. Postoperative examinations were done at
      1 day, 1 week, and 1, 3, 6, and 12 months. The mean follow-up was 10 months.
      RESULTS: Complet capsulorhexis was achieved in 26 cases. Intraoperative
      complications included incomplet capsulorhexis in four cases (13.3%) and
      conversion to a conventional extraction technique in two cases. There were no
      cases of posterior capsular tear. Twenty-eight eyes (93.3%) had a final best
      corrected visual acuity at 8/10 or better. Postoperative complications included
      moderate transient corneal edema in six cases (20%) and iritis in three cases
      (10%). There were no complications related to the use of trypan blue. CONCLUSION:
      Phacoemulsification using trypan blue was safe and effective in managing white
      cataract and had a high success rate.

PMID- 18046276
TI  - [Assessment of risk factors for retinal vein occlusions in patients under 60
      years of age].
AB  - PURPOSE: To assess the biologic factors contributing to the risk for
      cardiovascular and coagulation problems in patients under 60 years of age with
      retinal vein occlusions (RVOs) in order to determine the advantages of an
      exhaustive etiologic search. PATIENTS AND METHOD: Observational and retrospective
      study on 43 patients under the age of 60, 30 of whom presented central or
      hemicentral retinal vein occlusions; 13 were affected with branch retinal vein
      occlusions. All patients received a systematic check-up including blood pressure
      measurement, blood cholesterol level, carotid Doppler imaging, intraocular
      pressure measurement and glaucoma history, presence of thrombophilic factors
      (protein C/S, activated protein C resistance, antiphospholipid antibodies), and
      presence of disturbed homocysteine metabolism. A systemic medical history was
      also taken. RESULTS: The most frequent factors associated with central retinal
      vein occlusion (CRVO) were hyperhomocysteinemia (33%), arterial hypertension
      (23%), hypercholesterolemia (20%), open-angle glaucoma or intraocular
      hypertension (13%), and diabetes (10%). As for branch retinal vein occlusion, the
      only notable risk factors were arterial hypertension and hypercholesterolemia
      (46.2% and 38.5%, respectively). DISCUSSION: and conclusion: Our results are
      consistent with etiologic data of RVO already reported in the literature. They
      further underline that there is little advantage to an exhaustive etiologic
      investigation to detect thrombophilia in the absence of a suggestive medical
      history. Finally, our data suggest the benefit of checking for
      hyperhomocysteinemia, frequently found in patients with CRVO, and easily
      correctable with a vitamin supplement.

PMID- 18046277
TI  - [Use of MEOPA during nasolacrimal duct probing in children].
AB  - BACKGROUND: Congenital nasolacrimal duct obstruction affects more than 6% of
      newborns. Whereas some recommend nasolacrimal probing under general anesthesia
      from 1 year of age when the condition does not spontaneously resolve, some decide
      in favor of early probing from 4 to 6 months of age with topical anesthesia. We
      present nasolacrimal probing with inhalation of MEOPA, an equimolar mixture of
      nitrous oxide and oxygen, as a therapeutic alternative. PATIENTS AND METHODS: We
      conducted a descriptive, prospective study including 63 children (75 eyes) who
      had nasolacrimal duct probing with inhalation of MEOPA between March 2005 and
      March 2006, in consultation. Efficacy was estimated by the observation of medical
      staff and parents and by the feasibility of the probing procedure. RESULTS:
      Children were 4-28 months old (mean age, 11.5 months). Symptoms resolved
      spontaneously in 79% of cases after only one probing. No incident was observed.
      In case of failure, probing with nasolacrimal intubation with nasal endoscopy and
      general anesthesia was done (21% of cases, mean age, 17.5 months). DISCUSSION:
      Administration of MEOPA, by inhalation with a facial mask, is already used for
      minor pediatric surgical procedures. It is simple to use, fast, low-risk,
      inexpensive, and effective. CONCLUSION: Use of MEOPA in nasolacrimal duct probing
      in children could be a good alternative, making it possible to alleviate pain in
      the youngest children and general anesthesia in the oldest.

PMID- 18046278
TI  - [Natural development over 4 years of a macular small choroidal melanoma in a
      single-eyed patient].
AB  - We report the case of a single-eyed patient with a small (2.2 mm thick with
      largest tumor diameter 7.6 mm) choroidal melanoma involving the entire macular
      surface with few functional signs. Visual acuity was 20/63. The patient was
      informed of the side effects and so was followed regularly at the oncology unit
      over 4 years. During this period, the tumor volume increased fourfold (the
      thickness reached 4.3 mm and the LTD 10.4 mm), with visual acuity decreasing to
      20/250: proton beam therapy was therefore performed. The patient showed no
      metastasis more than 2 years after the treatment. This unusual case raises the
      question of small choroidal melanoma management, especially if the patient is
      single-eyed, in good general health, middle-aged and if the tumor is retrofoveal
      with just a few functional signs: when, why and who should be treated?

PMID- 18046279
TI  - [Fungal keratitis caused by Scedosporium apiospermum].
AB  - INTRODUCTION: We report a case of posttraumatic keratomycosis caused by
      Scedosporium apiospermum that was treated with oral and topical voriconazole and
      penetrating keratoplasty. CASE REPORT: A patient was admitted to the hospital
      with a corneal abscess of his right eye due to trauma while gardening. No
      improvement was noted with topical fortified antibiotics (vancomycin, gentamicin,
      and cefazolin) and antimycotic (amphotericin B 1%) and oral itraconazole (200
      mg/day). Fungal cultures of corneal scrapings revealed growth of Scedosporium
      apiospermum, a strain for which the main antifungals showed high minimal
      inhibitory concentrations (MICs), whereas the MIC of voriconazole was 0.125
      microg/mL. Despite some improvement with topical 1% voriconazole and oral
      voriconazole (200 mg/day) treatment, a therapeutic penetrating keratoplasty was
      performed because of the high risk of corneal perforation. The graft remained
      clear without fungal recurrence with topical 2% cyclosporine A, dexamethasone,
      and voriconazole treatment. CONCLUSION: Scedosporium apiospermum is an uncommon
      cause of mycotic keratitis in humans. Prognosis is generally poor because of
      delayed diagnosis and resistance to conventional antifungals. Voriconazole is a
      triazole broad-spectrum antifungal agent. In conjunction with its oral
      administration, topical application of voriconazole extends the current
      armamentarium of antifungal agents for keratomycosis.

PMID- 18046280
TI  - [Orbitotemporal segmental neurofibromatosis].
AB  - INTRODUCTION: Neurofibromatosis is a rare pathology with heterogeneous clinical
      presentation. OBSERVATION: We report a case of a right orbitotemporal plexiform
      neurofibroma in a 64-year-old woman with von Recklinghausen's neurofibromatosis.
      A craniofacial CT scan, with injection, showed a heterogeneous tumor in front of
      the skull base and the temporoparietal bone with no intracranial extension but an
      extension into the maxillary sinus and nasal cavity. In summery, she presented
      orbitotemporal segmental neurofibromatosis type 1 because of the unilateral
      lesion. She had a first surgery to remove her jugal and preauricular tumor with
      an exenteration, which provided an eye histology. The histology found no Lisch
      nodules but a cellular proliferation causing choroidal hyperplasia. We noted
      neurofibromin on choroidal cells and normal cells in addition to pathologic cells
      (Schwann cells and melanocytes), meaning that two cell populations were obtained
      in the same tissue: a somatic mosaicism. DISCUSSION/CONCLUSION: We advance the
      hypothesis that there was a regulation of cellular growth in a particular
      microenvironment because of the absence of tumor. To identify and confirm the
      somatic mosaicism, we would need a FISH analysis (probes containing sequences of
      the NF1 gene with a probe specific for the chromosome 17 centromere).

PMID- 18046281
TI  - [Glaucoma in the over-eighties].
AB  - Due to the recent rapid increase in the aging population, glaucoma in the over
      eighties population will become a significant problem of ocular health in the
      coming decades. It is important to determine the natural effects of aging on the
      optic nerve head and aqueous humor dynamics in these patients for early diagnosis
      and monitoring of glaucoma. Its characteristics, context, management, and
      treatment are very perceptibly different from those of the younger glaucomatous
      patient. For many reasons, such as its frequent association with macular age
      related degeneration, diagnosis of glaucoma in the over-eighties may be
      difficult. Management of the over-eighties glaucoma is frequently difficult and
      time-consuming. Less aggressive than in a younger patient and based on topical
      medications in most cases, it must be discussed case by case and will be based on
      the general context, the quality of compliance, and especially on the potential
      consequences of the glaucomatous visual-field defects on the patient's quality of
      life. In any case, overtreatment as well as treatments that are too complex must
      be avoided. Given the reduced metabolism in the very elderly, the safest
      medications must also be selected. It is important to always consider glaucoma
      medications as part of the patient's medicine regimen. Associated risk factors,
      especially concomitant systemic hypotension, will be simultaneously treated.
      Laser trabeculoplasties probably have broader indications than in younger
      patients. Except for phacoextraction, which is very frequently helpful in
      controlling IOP, incisional filtering procedures or laser diode
      cyclophotocoagulations remain infrequently indicated in over-eighties glaucoma
      patients.

PMID- 18046282
TI  - [Techniques for measuring phakic and pseudophakic accommodation. Methodology for
      distinguishing between neurological and mechanical accommodative insufficiency].
AB  - The methods available for studying accommodation are evaluated: Donder's "push
      up" method, dynamic retinoscopy, infrared optometry using the Scheiner principle,
      and wavefront analysis are each discussed with their inherent advantages and
      limitations. Based on the methodology described, one can also distinguish between
      causes of accommodative insufficiency. Dioptric insufficiency (accommodative lag)
      that remains equal at various testing distances from the subject indicates a
      sensory/neurologic (afferent), defect, whereas accommodative insufficiency
      changing with distance indicates a mechanical/restrictive (efferent) defect, such
      as in presbyopia. Determining accommodative insufficiency and the cause can be
      particularly useful when examining patients with a variety of diseases associated
      with reduced accommodative ability (e.g., Down syndrome and cerebral palsy) as
      well as in evaluating the effectiveness of various potentially accommodating
      intraocular lens designs.

PMID- 18046284
TI  - [Drusen of the optic disc].

PMID- 18046283
TI  - [MALT (mucosa-associated lymphoid tissue) lymphoma of the lacrimal gland].
AB  - MALT lymphoma of the lacrimal gland is rare. Orbital involvement is usually
      located on the anterior orbit. We report the case of a 65-year-old man consulting
      for an eyelid tumor located on the right upper and lateral lid, which clinically
      recalled lacrimal gland involvement. The gland biopsy and the immunohistochemical
      analysis concluded in the diagnosis of B and MALT lymphoma. The assessment of the
      ganglion and extra-ganglion enlargement of these lymphomas is of capital
      importance in treatment. A multidisciplinary analysis, especially oncological, is
      important so that the best therapeutic plan can be adopted.

PMID- 18046285
TI  - Levocetirizine (Xyzal) for allergic rhinitis and urticaria.

PMID- 18046286
TI  - Major changes in endocarditis prophylaxis for dental, GI and GU procedures.

PMID- 18046289
TI  - When is prolonged intubation after cardiac surgery really unavoidable?

PMID- 18046290
TI  - Analgesia before, during and after surgery: prevention of postoperative pain.

PMID- 18046291
TI  - Predictors of prolonged mechanical ventilation in a cohort of 3,269 CABG
      patients.
AB  - BACKGROUND: Prolonged mechanical ventilation after heart surgery is associated
      with increased patient morbidity and mortality (4.9% vs 22-38%). A prospective
      observational cohort study was carried out to assess the predictors of prolonged
      mechanical ventilation and its impact on hospital survival in a cardiac surgical
      patient cohort admitted to our 8 bed postoperative ICU from January 1997 through
      June 2004. METHODS: All of the patient perioperative and ICU variables were input
      into an electronic database. Patients were divided into: 1) an Early Extubation
      group, undergoing a successful extubation within 12 h and 2) a Delayed Extubation
      group, needing mechanical ventilation longer than 12 h. RESULTS: A total of 3,269
      patients undergoing a coronary artery bypass graft operation were admitted. A
      multivariate Logistic Regression model allowed us to identify: 1) redo surgery
      (OR = 3.090, 95% CI = 1.655-5.780); 2) cardiopulmonary bypass time longer than
      91' (OR = 1.390, 95% CI = 1.013-1.908); 3) intraoperative transfusions of more
      than 4 units of red blood cells (OR = 3.144, 95% CI = 2.331-4.255) or fresh
      frozen plasma (OR = 2.976, 95% CI = 1.984-4.830); and 4) left ventricular
      ejection fraction = or < 30% (OR = 2.444, 95% CI 1.291-3.205) as independent
      predictors of prolonged mechanical ventilation. The Early Extubation group showed
      a significantly higher cumulative survival 180 days after the ICU admission (Log
      Rank = 16.617, p=0.000). CONCLUSION: This audit allowed us to assess a predictive
      model identifying a priori coronary artery bypass graft patients that are more
      likely to undergo prolonged mechanical ventilation.

PMID- 18046292
TI  - The analgesic efficacy of tramadol in ambulatory gynecological laparoscopic
      procedures: a randomized controlled trial.
AB  - BACKGROUND: To evaluate the postoperative analgesic efficacy of intravenous
      tramadol 50 mg administered before anesthetic induction in patients undergoing
      ambulatory gynecological laparoscopic procedures. METHODS: This was a double
      blind randomized, controlled trial conducted in 150 patients. Pain intensity was
      measured using a verbal numerical rating score at 1, 2, 6, 12, and 24 h
      postoperatively and at discharge. Requirement of analgesics (fentanyl and
      paracetamol), effect of pain on sleep, activity limitation, side effects
      (headache, dizziness, drowsiness, nausea, vomiting, and dry mouth), global
      perceived analgesic efficacy, satisfaction, and preference for stronger
      analgesics were assessed in the first 24 h postoperatively. RESULTS: There were
      no statistical differences between the tramadol group and the placebo group in
      terms of clinical data and pain intensity at any measured times. Recovery room
      data showed no statistical differences regarding number of patients requiring
      fentanyl, time to first fentanyl requirement, total fentanyl required, verbal
      numerical rating score before fentanyl administration, and incidence of
      nausea/vomiting and shivering. Post-discharge data showed that patients in the
      tramadol group required statistically less paracetamol (3.2 vs. 3.9 tablets, P =
      0.04). There were no statistical differences regarding the number of patients
      requiring paracetamol, verbal numerical rating score before taking paracetamol,
      effect of pain on sleep and activity, global perceived analgesic efficacy,
      satisfaction, preference for stronger analgesics, and side effects. CONCLUSION:
      Intravenous tramadol 50 mg given before anesthetic induction did not reduce pain
      intensity but was well tolerated. Although tramadol statistically reduced the
      paracetamol requirement in the first 24 h postoperatively, it did not seem to
      provide a significant clinical advantage.

PMID- 18046293
TI  - Subhypnotic doses of midazolam prevent nausea and vomiting during spinal
      anesthesia for cesarean section.
AB  - BACKGROUND: We aimed to evaluate the efficacy of subhypnotic doses of midazolam
      and propofol for peripartum nausea and vomiting during regional anesthesia for
      elective cesarean section in order to prevent emesis in at least 50% of patients.
      METHODS: A prospective, double blind, placebo-controlled study was carried out.
      Patients were randomly allocated to one of three groups to receive placebo
      (saline, N=28), propofol (20 mg bolus and 1.0 mg x kg(-1) x h(-1) infusion,
      N=30), and midazolam (1 mg bolus and 1.0 mg x h(-1) infusion, N=30) at
      subhypnotic doses intravenously (i.v.) immediately after the umbilical cord was
      clamped. Bupivacaine hydrochloride (8-10 mg) and fentanyl (10 microg) were
      injected into the intervertebral space for spinal anesthesia. Blood pressure was
      monitored at 2 min intervals and intraoperative postdelivery emetic episodes and
      ephedrine consumption were recorded. The study was carried out at the
      Anesthesiology Department, Hacettepe University, Turkey, hospitalized care. We
      included 90 parturients with ASA physical status I and II between the ages of 20
      and 38 years undergoing spinal anesthesia for elective cesarean delivery to
      evaluate the efficacy of subhypnotic doses of propofol and midazolam and, in
      particular, the incidence of nausea, retching, and vomiting intraoperatively.
      RESULTS: The incidence of nausea, retching, and vomiting was significantly higher
      in the control group, compared to the propofol and midazolam groups. Total
      ephedrine consumption was significantly higher in the control group compared to
      the propofol and midazolam groups. CONCLUSION: A subhypnotic dose of midazolam (1
      mg x h(-1)) was as effective as the subhypnotic dose of propofol (1 mg x kg(-1) x
      h(-1)) for the prevention of nausea and vomiting in parturients undergoing
      cesarean section under spinal anesthesia.

PMID- 18046294
TI  - Critical care of HIV infected patients in the highly active antiretroviral
      therapy era.
AB  - Since there are more than 150 000 Italians (about 25 for every 10,000
      inhabitants) infected with HIV, Intensive Care Units (ICU) often come across
      patients who are HIV positive. The aim of this study was to provide current
      information on the epidemiology of human immunodeficiency virus (HIV)-infected
      patients admitted to ICU during the era of highly active antiretroviral therapy
      (HAART) and to review issues related to the administration of antiretroviral
      therapy relevant to the ICU staff. Overall mortality of critically ill HIV
      infected patients in ICUs has decreased in the HAART era, and patients are more
      often admitted with non-HIV-related illnesses. Use of HAART in the ICU is
      difficult; however it may be associated with improved outcomes. More HIV-infected
      patients survive ICU admission and are less likely to be admitted to the ICU for
      related infections; in most cases, they need critical care for problems unrelated
      to HIV infection or for conditions related to HAART toxicity. ICU staff need to
      be familiar with HAART for the following reasons: 1) to recognize life
      threatening toxicities unique to these drugs; 2) to avoid drug interactions,
      which are extremely common and potentially life-threatening; and 3) to avoid
      enhancing HIV drug resistance, an occurrence that could have devastating
      consequences for the patient after discharge from the ICU.

PMID- 18046295
TI  - My brother has severe sepsis--should he receive Xigris?
AB  - Six years ago, a publication in a quite well known scientific medical journal
      brought hope and a good dose of optimism to sepsis therapy and the critical care
      community. For the first time, a careful randomized controlled trial in patients
      with severe sepsis or septic shock seemed to show a clearly beneficial effect of
      a new drug, i.e. of activated recombinant human protein C. This new treatment
      possibility was welcomed as an important breakthrough and a hope for a better
      management of a deadly disease. However, further evaluation of the results of the
      trial and new investigations did not confirm entirely the initial optimism. As a
      consequence, the adequate indications for this expensive drug remain
      controversial.

PMID- 18046296
TI  - Spinal cord infarction following surgery for mesenteric vascular occlusion.
AB  - We present a case of spinal cord infarction following an operation on a 64-year
      old man for mesenteric vascular occlusion under combined general and epidural
      anesthesia. Several etiological factors, each one able to affect blood flow in
      the spinal cord and cause infarction, might have been present in our patient,
      including generalized degenerative atherosclerotic vascular disease, secondary
      polycythemia resulting from the patient's chronic obstructive pulmonary disease,
      and intraoperative hypotensive episodes. This case shows that, even with careful
      technique, hemodynamic monitoring, and early evaluation of neurologic status,
      patients can experience irreversible spinal cord ischaemia that results in
      permanent paraplegia.

PMID- 18046297
TI  - Acute left ventricular dysfunction due to Tako-tsubo syndrome after induction of
      general anesthesia.
AB  - Tako-tsubo cardiomyopathy is a recently described form of transient ventricular
      dysfunction that is not associated with coronary vessels obstruction, although
      its clinical manifestations are often similar to those of myocardial ischemia.
      This syndrome is possibly due to an excess of catecholamines, and it is
      associated with emotional and physical stress and surgery. However, the
      pathophysiological relation to anaesthesia has not yet been clarified. We report
      a case of Tako-tsubo cardiomyopathy that ensued immediately after induction of
      general anaesthesia for elective surgery in a patient submitted to laparoscopic
      cholecystectomy. The patient was first treated as if affected by myocardial
      ischemia, but a rapidly performed emergency coronary angiography showed normal
      epicardial coronary vessels with a significant reduction of left ventricular
      function. The coronary angiography ruled out the diagnosis of typical myocardial
      ischemia and allowed for the arrival at the correct diagnosis. The transient
      ventricular ballooning was attributed to the recently described Tako-tsubo
      syndrome. Prompt treatment allowed control of symptoms, and the patient was
      safely treated and discharged on day 15. Although it is difficult to identify the
      cause of this syndrome, it may be argued that, during general anaesthesia and
      particularly at induction, the imperfect control of catecholamine excess may
      induce cardiac damage in predisposed subjects.

PMID- 18046298
TI  - Guiding management in perioperative methemoglobinemia.

PMID- 18046300
TI  - Rapid HIV testing in outreach and other community settings--United States, 2004
      2006.
AB  - In 2003, an estimated 1 million persons in the United States were living with
      human immunodeficiency virus (HIV) infection. Approximately 25% were unaware of
      their infection; however, that percentage might have been greater among persons
      at high risk for HIV infection, including racial/ethnic minority populations. To
      increase the proportion of persons aware of their HIV serostatus, CDC launched
      the Advancing HIV Prevention initiative in 2003. One strategy of the initiative
      is to implement new models for diagnosing HIV infections outside medical
      settings. During 2004-2006, CDC funded a demonstration project to provide rapid
      HIV testing and referral to medical care, targeted to racial/ethnic minority
      populations and others at high risk in outreach and other community settings.
      This report summarizes the results of that project, which indicated that, of
      23,900 clients who received a rapid HIV test, 39% were non-Hispanic blacks, 31%
      were Hispanics, 17% reported male-male sex, and 6% were injection-drug users. A
      total of 267 (1%) persons had confirmed HIV-positive test results; of these, 195
      (74%) were either non-Hispanic blacks or Hispanics. The project results
      demonstrate that rapid HIV testing in outreach and other community settings can
      identify large numbers of persons in racial/ethnic minority populations and
      others at high risk who are unaware they are infected with HIV.

PMID- 18046301
TI  - Progress in global measles control and mortality reduction, 2000-2006.
AB  - The World Health Organization (WHO) and United Nations Children's Fund (UNICEF)
      comprehensive strategy for measles mortality reduction is focused on 47 priority
      countries. Components include 1) achieving and maintaining high coverage (>90%)
      with the first dose of measles vaccine by age 12 months in every district of each
      priority country through routine immunization services; 2) ensuring that all
      children receive a second opportunity for measles vaccination; 3) maintaining
      effective case-based surveillance and monitoring of vaccination coverage; and 4)
      providing appropriate clinical management, including vitamin A supplementation.
      In 2005, the World Health Assembly set a goal for global measles control as part
      of the Global Immunization Vision and Strategy (GIVS): a 90% reduction in measles
      mortality by 2010, compared with 2000 levels. In January 2007, WHO/UNICEF
      reported that implementation of measles mortality reduction strategies had
      reduced measles mortality by 60%, from an estimated 873,000 deaths in 1999 to
      345,000 deaths in 2005. This reduction exceeded the goal of 50% measles mortality
      reduction by 2005 (compared with 1999 levels) that had been set in 2002. This
      report updates previous reports by detailing 1) measles mortality reduction
      activities implemented during 2006 and 2) the impact of activities since 2000 on
      the global burden of measles and progress toward the GIVS mortality reduction
      goal for 2010.

PMID- 18046302
TI  - Effects on violence of laws and policies facilitating the transfer of youth from
      the juvenile to the adult justice system: a report on recommendations of the Task
      Force on Community Preventive Services.
AB  - The independent, nonfederal Task Force on Community Preventive Services (Task
      Force), which directs the development of the Guide to Community Preventive
      Services (Community Guide), conducted a systematic review of published scientific
      evidence concerning the effectiveness of laws and policies that facilitate the
      transfer of juveniles to the adult criminal justice system to determine whether
      these transfers prevent or reduce violence among youth who have been transferred
      and among the juvenile population as a whole. For this review, transfer is
      defined as placing juveniles aged <18 years under the jurisdiction of the adult
      criminal justice system. The review followed Community Guide methods for
      conducting a systematic review of literature and for providing recommendations to
      public health decision makers. Available evidence indicates that transfer to the
      adult criminal justice system typically increases rather than decreases rates of
      violence among transferred youth. Available evidence was insufficient to
      determine the effect of transfer laws and policies on levels of violent crime in
      the overall juvenile population. On the basis of these findings, the Task Force
      recommends against laws or policies facilitating the transfer of juveniles to the
      adult criminal justice system for the purpose of reducing violence.

PMID- 18046303
TI  - Disruption of AMPA receptor endocytosis impairs the extinction, but not
      acquisition of learned fear.
AB  - Synaptic plasticity in the form of long-term potentiation (LTP) plays a critical
      role in the formation of a Pavlovian fear association. However, the role that
      synaptic plasticity plays in the suppression of a learned fear response remains
      to be clarified. Here, we assessed the role that long-term depression (LTD) plays
      in the acquisition, expression, and extinction of a conditioned fear response. We
      report that blockade of LTD with a GluR2-derived peptide (Tat-GluR2(3Y); 1.5
      micromol/kg, i.v.) that blocks regulated alpha-amino-3-hydroxy-5-methyl-isoxazole
      4-propionic acid (AMPA) receptor endocytosis during an initial extinction
      training session disrupted both the expression and recall of extinction learning.
      A similar impairment of extinction during training, but not recall, was observed
      when NMDA receptor-dependent LTD was inhibited through the selective blockade of
      NMDA NR2B receptors with Ro 25-6981. In contrast, blockade of LTD with Tat
      GluR2(3Y) during fear conditioning or during a fear recall test did not effect
      the expression or recall of either contextual or cue-induced conditioned fear.
      Similarly, administration of Tat-GluR2(3Y) prior to an extinction recall test did
      not affect spontaneous recovery or rate of re-extinction in previously
      extinguished rats. These data demonstrate that AMPA receptor endocytosis does not
      mediate acquisition or expression of conditioned fear, but may play a role in the
      extinction of fear memories. Furthermore, these findings suggest that LTD may be
      a molecular mechanism that facilitates the selective modification of a learned
      association while leaving intact the ability to form a new memory.

PMID- 18046304
TI  - Chronic lithium salt treatment reduces CRE/CREB-directed gene transcription and
      reverses its upregulation by chronic psychosocial stress in transgenic reporter
      gene mice.
AB  - The molecular mechanism of action of the mood stabilizer lithium is assumed to
      involve changes in gene expression leading to neuronal adaptation. The
      transcription factor CREB (cAMP-responsive element binding protein) regulates the
      expression of many genes and has been implicated in important brain functions and
      the action of psychogenic agents. We here investigated the effect of lithium on
      cAMP-responsive element (CRE)/CREB-mediated gene transcription in the brain,
      using transgenic reporter mice that express the luciferase reporter gene under
      the control of four copies of the rat somatostatin gene promoter CRE. Chronic (21
      days) but not acute (24 h) treatment with lithium (7.5 mmol/kg) significantly
      decreased CRE/CREB-directed gene expression in hippocampus, cortex, hypothalamus,
      and striatum to 60-70%, and likewise reduced CREB phosphorylation. As bipolar
      disorder is also considered as a stress-related disorder, the effect of lithium
      was determined in mice submitted to a paradigm for chronic psychosocial stress.
      As shown before, stress for 25 days significantly increased CRE/CREB-directed
      gene expression in several brain regions by 100-150%. Treatment of stressed mice
      with lithium decreased stress-induced CRE/CREB-directed gene expression to
      control levels in nearly all brain regions and likewise reduced CREB
      phosphorylation. Chronic lithium treatment induced beta-catenin accumulation and
      decreased cAMP levels, indicating an inhibitory effect of lithium on glycogen
      synthase kinase 3 and the adenylate cyclase/protein kinase A signalling cascade,
      which are known to modulate CREB activity. We here for the first time show that
      lithium regulates CRE/CREB-directed gene transcription in vivo and suggest CREB
      as a putative mediator of the neuronal adaptation after chronic lithium
      treatment.

PMID- 18046306
TI  - Spatial attentional bias as a marker of genetic risk, symptom severity, and
      stimulant response in ADHD.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a heritable childhood onset
      disorder that is marked by variability at multiple levels including clinical
      presentation, cognitive profile, and response to stimulant medications. It has
      been suggested that this variability may reflect etiological differences,
      particularly, at the level of underlying genetics. This study examined whether an
      attentional phenotype-spatial attentional bias could serve as a marker of symptom
      severity, genetic risk, and stimulant response in ADHD. A total of 96 children
      and adolescents with ADHD were assessed on the Landmark Task, which is a
      sensitive measure of spatial attentional bias. All children were genotyped for
      polymorphisms (3' untranslated (UTR) and intron 8 variable number of tandem
      repeats (VNTRs)) of the dopamine transporter gene (DAT1). Spatial attentional
      bias correlated with ADHD symptom levels and varied according to DAT1 genotype.
      Children who were homozygous for the 10-repeat allele of the DAT1 3'-UTR VNTR
      displayed a rightward attentional bias and had higher symptom levels compared to
      those with the low-risk genotype. A total of 26 of these children who were
      medication naive performed the Landmark Task at baseline and then again after 6
      weeks of stimulant medication. Left-sided inattention (rightward bias) at
      baseline was associated with an enhanced response to stimulants at 6 weeks.
      Moreover, changes in spatial bias with stimulant medications, varied as a
      function of DAT1 genotype. This study suggests an attentional phenotype that
      relates to symptom severity and genetic risk for ADHD, and may have utility in
      predicting stimulant response in ADHD.

PMID- 18046307
TI  - Opposing roles for 5-HT2A and 5-HT2C receptors in the nucleus accumbens on
      inhibitory response control in the 5-choice serial reaction time task.
AB  - Serotonin (5-HT) is thought to play an important role in the regulation of
      behavioral inhibition. Studies manipulating 5-HT function in the rodent brain
      indicate that 5-HT receptors regulate distinct forms of impulsive behavior,
      including impulsive responding in the 5-choice serial reaction time task
      (5CSRTT). The present study investigates the loci of effects mediated by 5-HT(2A)
      and 5-HT(2C) receptors in attention and inhibitory response control using
      microinfusions targeted at the nucleus accumbens (NAc), prelimbic cortex (PL) and
      infralimbic cortex (IL). Rats were implanted with bilateral guide cannulas and
      received infusions of the selective 5-HT(2A) receptor antagonist M100907 (0.1 and
      0.3 microg) or selective 5-HT(2C) receptor antagonist SB242084 (0.1 and 0.5
      microg) immediately prior to testing. The results show that intra-NAc infusions
      of M100907 significantly decrease impulsive responding on the 5CSRTT and at the
      highest dose increased omissions as well. By contrast, infusions of SB242084 into
      the NAc selectively and dose-dependently increased impulsivity. Neither M100907
      nor SB242084 significantly altered impulsive responding following either intra-PL
      or intra-IL administration. However, SB242084 significantly decreased omissions
      following intra-PL administration (0.5 microg only). These data reveal opposing
      effects on impulsivity following 5-HT(2A) and 5-HT(2C) blockade in the NAc. Our
      results suggest that the NAc, but not the PL or IL, is implicated in the
      mediation of the effects of M100907 and SB242084 on inhibitory response control
      during baseline 5CSRTT performance.

PMID- 18046305
TI  - The evolution of drug development in schizophrenia: past issues and future
      opportunities.
AB  - Schizophrenia is a disease syndrome with major public health implications. The
      primary advance in pharmacotherapeutics was in 1952 with the introduction of
      antipsychotic medications (ie, chlorpromazine, dopamine D2 antagonism). Barriers
      to progress have been substantial, but many will be subject to rapid change based
      on current knowledge. There are attractive psychopathology indications for drug
      discovery (eg, impaired cognition and negative symptoms), and drugs with efficacy
      in these domains may have application across a number of disease classes. These
      pathologies are observed prior to psychosis raising the possibility of very early
      intervention and secondary prevention. Success in drug discovery for cognition
      and negative symptom pathologies may bring forth issues in ethics as the
      potential for enhancing normal function is explored.

PMID- 18046308
TI  - Alpha1-adrenergic receptor-induced heterosynaptic long-term depression in the bed
      nucleus of the stria terminalis is disrupted in mouse models of affective
      disorders.
AB  - The glutamatergic synapse in specific brain regions has been shown to be a site
      for convergence of stress and addictive substances. The bed nucleus of the stria
      terminalis (BNST), a nucleus that relays between higher order processing centers
      and classical reward and stress pathways, receives dense noradrenergic inputs
      that are known to influence behavioral paradigms of both anxiety and stress
      induced relapse to drug seeking. Alpha(1)-adrenergic receptors (alpha(1)-ARs)
      within this region have been implicated in modulation of the HPA axis and anxiety
      responses. We found that application of an alpha(1)-AR agonist produced a long
      term depression (LTD) of excitatory transmission in an acute mouse BNST slice
      preparation. This effect was mimicked by a 20 min, but not a 10 min, application
      of 100 microM norepinephrine (NE) in a prazosin-sensitive manner. This alpha(1)
      AR LTD was independent of N-methyl-D-aspartate receptor (NMDAR) function unlike
      previously described alpha(1)-AR LTD in the hippocampus and visual cortex;
      however, it was dependent on the activation of L-type voltage gated calcium
      channels (VGCCs). In addition, alpha(1)-AR LTD was induced independently of the
      activation of mGluR5 which can also induce LTD in this region. Furthermore,
      alpha(1)-AR LTD was intact in mice receiving an intraperitoneal injection of
      cocaine but was disrupted in alpha(2a)-AR and NE transporter (NET) knockout (KO)
      mice. Thus a loss of this plasticity at glutamatergic synapses in BNST could
      contribute to affective behavioral phenotypes of these mice.

PMID- 18046310
TI  - Activation of kainate GLU(K5) transmission rescues kindling-induced impairment of
      LTP in the rat lateral amygdala.
AB  - The amygdala is a component of the limbic system that plays a central role in
      emotional behavior and certain psychiatric diseases. Pathophysiological
      alterations of neuronal excitability in the amygdala are characteristic features
      of temporal lobe epilepsy and certain (epilepsy accompanying) psychiatric
      illnesses such as anxiety and depressive disorders. The role of kainate receptors
      in the activity of synaptic networks, in brain function, and diseases is still
      poorly understood. Various kainate receptor subtypes have been shown to
      contribute to synaptic transmission and modulate presynaptic release of glutamate
      and gamma-aminobutyric acid (GABA). Several lines of evidence point to the
      importance of GLU(K5) kainate receptors in epilepsy. In this study we
      investigated the role of specific GLU(K5) kainate receptor in the lateral nucleus
      of the amygdala (LA). The cellular mechanisms for emotional learning in the
      amygdala are believed to be the result of changes in synaptic transmission
      efficacy, similar to long-term potentiation (LTP). Here, we used both field
      potential and intracellular recordings in horizontal rat amygdala slices, and
      showed that LTP in the LA, induced by high-frequency stimulation of afferents
      running within LA, is impaired 48 h after the last induced seizure. This kindling
      induced impairment was reversed by the specific kainate GLU(K5) agonist ATPA.
      Partial blockade of GABAergic transmission with the specific GABA(A) receptor
      antagonist SR95531 also significantly facilitated the induction of early LA-LTP,
      but only partially abolished the kindling-induced impairment of LA-LTP. This
      study shows that the stimulation of the GLU(K5) kainate receptor subtype rescues
      the kindling-induced impairment of LA-LTP at least within 48 h after the last
      seizure. Therefore, GLU(K5) kainate receptor subunits are involved in kindling
      induced plasticity changes in the amygdala.

PMID- 18046309
TI  - Tolerance to repeated morphine administration is associated with increased
      potency of opioid agonists.
AB  - Tolerance to the pain-relieving effects of opiates limits their clinical use.
      Although morphine tolerance is associated with desensitization of mu-opioid
      receptors, the underlying cellular mechanisms are not understood. One problem
      with the desensitization hypothesis is that acute morphine does not readily
      desensitize mu-opioid receptors in many cell types. Given that neurons in the
      periaqueductal gray (PAG) contribute to morphine antinociception and tolerance,
      an understanding of desensitization in PAG neurons is particularly relevant.
      Opioid activity in the PAG can be monitored with activation of G-protein-mediated
      inwardly rectifying potassium (GIRK) currents. The present data show that opioids
      have a biphasic effect on GIRK currents in morphine tolerant rats. Opioid
      activation of GIRK currents is initially potentiated in morphine (EC(50)=281 nM)
      compared to saline (EC(50)=8.8 microM) pretreated rats as indicated by a leftward
      shift in the concentration-response curve for met-enkephalin (ME)-induced
      currents. These currents were inhibited by superfusion of the mu-opioid receptor
      antagonist beta-funaltrexamine (beta-FNA) suggesting that repeated morphine
      administration enhances agonist stimulation of mu-opioid receptor coupling to G
      proteins. Although supersensitivity of mu-opioid receptors in the PAG is
      counterintuitive to the development of tolerance, peak GIRK currents from
      tolerant rats desensitized more than currents from saline pretreated rats (56% of
      peak current after 10 min compared to 15%, respectively). These data indicate
      that antinociceptive tolerance may be triggered by enhanced agonist potency
      resulting in increased desensitization of mu-opioid receptors.

PMID- 18046311
TI  - Role of beta-adrenoceptors in memory consolidation: beta3-adrenoceptors act on
      glucose uptake and beta2-adrenoceptors on glycogenolysis.
AB  - Noradrenaline, acting via beta(2)- and beta(3)-adrenoceptors (AR), enhances
      memory formation in single trial-discriminated avoidance learning in day-old
      chicks by mechanisms involving changes in metabolism of glucose and/or glycogen.
      Earlier studies of memory consolidation in chicks implicated beta(3)- rather than
      beta(2)-ARs in enhancement of memory consolidation by glucose, but did not
      elucidate whether stimulation of glucose uptake or of glycolysis was responsible.
      This study examines the role of glucose transport in memory formation using
      central injection of the nonselective facilitative glucose transporter (GLUT)
      inhibitor cytochalasin B, the endothelial/astrocytic GLUT-1 inhibitor phloretin
      and the Na(+)/energy-dependent endothelial glucose transporter (SGLT) inhibitor
      phlorizin. Cytochalasin B inhibited memory when injected into the mesopallium
      (avian cortex) either close to or between 25 and 45 min after training, whereas
      phloretin and phlorizin only inhibited memory at 30 min. This suggested that
      astrocytic/endothelial (GLUT-1) transport is critical at the time of
      consolidation, whereas a different transporter, probably the neuronal glucose
      transporter (GLUT-3), is important at the time of training. Inhibition of glucose
      transport by cytochalasin B, phloretin, or phlorizin also interfered with beta(3)
      AR-mediated memory enhancement 20 min posttraining, whereas inhibition of
      glycogenolysis interfered with beta(2)-AR agonist enhancement of memory. We
      conclude that in astrocytes (1) activities of both GLUT-1 and SGLT are essential
      for memory consolidation 30 min posttraining; (2) neuronal GLUT-3 is essential at
      the time of training; and (3) beta(2)- and beta(3)-ARs consolidate memory by
      different mechanisms; beta(3)-ARs stimulate central glucose transport, whereas
      beta(2)-ARs stimulate central glycogenolysis.

PMID- 18046313
TI  - Nephrin is involved in podocyte maturation but not survival during glomerular
      development.
AB  - Nephrin, a major component of the glomerular slit diaphragm (SD), is both a
      structural protein as well as a signaling molecule influencing foot process (FP)
      formation and maintenance of podocyte integrity. Analyses of near-term embryonic
      kidneys showed normal cellular viability and no apoptosis in glomeruli from
      nephrin knockout mice. Moreover, expression and location of other SD or
      glomerular basement membrane components were similar in wild-type and mutant mice
      as was the location and levels of most podocyte-specific proteins.
      Transcriptional profiling showed that the lack of nephrin had minor impact on the
      expression of genes for FPs and SD proteins. Claudin 3, a tight-junction protein
      normally absent in glomeruli, was upregulated threefold in the knockout mice,
      suggesting a role of nephrin in claudin 3 gene expression within the glomeruli.
      Our results suggest that nephrin is expressed late in the process of podocyte
      differentiation and is a locus for the formation of SD and FP maintenance and
      physical integrity in vivo. Nephrin does not seem to have a primary role in cell
      survival but has a small impact on gene regulation during glomerular development.

PMID- 18046312
TI  - Metabotropic glutamate 5 receptor (mGluR5) antagonists decrease nicotine seeking,
      but do not affect the reinforcement enhancing effects of nicotine.
AB  - Nicotine self-administration models typically evaluate the effects of smoking
      cessation aides on 'primary reinforcement' engendered by nicotine. However, the
      more recently described reinforcement enhancing effects of the drug are not
      always included in experimental analyses of potential therapeutics. We evaluated
      the effects of pretreatment with noncompetitive antagonists of the metabotropic
      glutamate 5 receptor (mGluR5) on each reinforcement-related effect of nicotine
      using a model in which a reinforcing visual stimulus (VS) and nicotine infusions
      were concurrently available. Five groups (2-lever, VS-only, NIC+VS, NIC-only, or
      SAL-only) were instrumented for self-administration. The 2-lever group could earn
      a nicotine infusion (0.06 mg/kg per infusion free base) for meeting the schedule
      on one lever (eg right), or VS for meeting the schedule on the other lever (eg
      left). The VS-only group could earn VS or saline under similar contingencies.
      Remaining rats could press one lever to earn both reinforcers (NIC+VS), nicotine
      infusions (NIC-only), or saline infusions (SAL-only); the other lever was
      'inactive'. Responding on the VS lever in the 2-lever group was greater than that
      of the VS-only group, reflecting the reinforcement-enhancing effect of nicotine.
      Pretreatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP) or 3-[(2-methyl-1,3
      thiazol-4-yl)ethynyl]pyridine (MTEP) decreased nicotine intake as well as the
      enhanced responding for the concurrently available VS. In follow-up studies,
      replacing nicotine via experimenter-administered infusions sustained the drugs
      reinforcement enhancing effect; neither MPEP nor MTEP decreased the enhancing
      effects of nicotine. These findings are consistent with other studies suggesting
      that mGlu5 receptors mediate nicotine seeking, but do not alter the reinforcement
      enhancing effects of nicotine.

PMID- 18046314
TI  - Reduction of anionic sites in the glomerular basement membrane by heparanase does
      not lead to proteinuria.
AB  - Heparan sulfate in the glomerular basement membrane has been considered crucial
      for charge-selective filtration. In many proteinuric diseases, increased
      glomerular expression of heparanase is associated with decreased heparan sulfate.
      Here, we used mice overexpressing heparanase and evaluated the expression of
      different heparan sulfate domains in the kidney and other tissues measured with
      anti-heparan sulfate antibodies. Glycosaminoglycan-associated anionic sites were
      visualized by the cationic dye cupromeronic blue. Transgenic mice showed a
      differential loss of heparan sulfate domains in several tissues. An unmodified
      and a sulfated heparan sulfate domain resisted heparanase action in vivo and in
      vitro. Glycosaminoglycan-associated anionic sites were reduced about fivefold in
      the glomerular basement membrane of transgenic mice, whereas glomerular
      ultrastructure and renal function remained normal. Heparanase-resistant heparan
      sulfate domains may represent remnant chains or chains not susceptible to
      cleavage. Importantly, the strong reduction of glycosaminoglycan-associated
      anionic sites in the glomerular basement membrane without development of a clear
      renal phenotype questions the primary role of heparan sulfate in charge-selective
      filtration. We cannot, however, exclude that overexpression of heparanase and
      heparan sulfate loss in the basement membrane in glomerular diseases contributes
      to proteinuria.

PMID- 18046315
TI  - Automated and continuous ambulatory peritoneal dialysis have similar outcomes.
AB  - We compared survival and death-censored technique survival in patients on
      automated peritoneal dialysis (automated dialysis) or on continuous ambulatory
      peritoneal dialysis. All 4128 patients from the Australia and New Zealand
      Dialysis and Transplant Registry who started peritoneal dialysis over a 5-year
      period through March 2004 were included. Times to death and death-censored
      technique failure were analyzed by Cox proportional hazards models while a
      conditional risk set model computed technique failure. Compared to patients
      treated entirely with continuous ambulatory peritoneal dialysis, automated
      peritoneal dialysis patients were more likely to be young, Caucasian, have
      marginally lower body mass index, and were less likely to have baseline
      cardiovascular disease or diabetes. Using univariate and multivariate analysis,
      our study showed there were no significant differences in patient survival and
      death-censored technique failure between the two types of peritoneal dialysis
      modalities.

PMID- 18046316
TI  - Interactions of the growth-related, type IIc renal sodium/phosphate cotransporter
      with PDZ proteins.
AB  - Despite similar molecular structures, the growth-related sodium/phosphate
      cotransporter NaPiIIc is regulated differently than the main NaPiIIa phosphate
      transporter. Using two-hybrid systems and immunoprecipitation, we identified
      several proteins that interact with NaPiIIc that might account for this
      differential regulation. NaPiIIc interacted with the PDZ domain-containing sodium
      hydrogen exchange-regulating factor (NHERF) 1 and NHERF3 through novel binding
      motifs in its C terminus. NaPiIIc from brush-border membranes coprecipitated with
      both NHERF1 and NHERF3, with more NHERF3 co-precipitated in rats fed a low
      phosphorus diet. NaPiIIc colocalizes with both NHERF1 and NHERF3 in brush-border
      membranes of rats fed either a low- or high-phosphorus diet. When mouse NaPiIIc
      was transfected into opossum kidney cells, it was localized mainly in apical
      microvilli and the trans-Golgi. Both confocal and total internal reflection
      microscopy show that NaPiIIc colocalizes with NHERF1 and NHERF3 in the apical
      microvilli, and this was not altered by truncation of the last three amino acids
      of NaPiIIc. Interactions of NaPiIIc with NHERF1 and NHERF3 were modulated by the
      membrane-associated 17 kDa protein (MAP17) similarly to NaPiIIa, but only the
      MAP17-NaPiIIc-NHERF3 complexes were internalized to the trans-Golgi. Our study
      shows that NaPiIIc interacts with a limited number of PDZ domain proteins, and
      the mechanisms and consequences of such interactions differ from those of
      NaPiIIa.

PMID- 18046317
TI  - The phosphoinositide-3 kinase gamma-Akt pathway mediates renal tubular injury in
      cisplatin nephrotoxicity.
AB  - Nephrotoxicity is a frequent complication of cisplatin-based chemotherapy often
      limiting its use. In this study, we attempted to the role of the phosphoinositide
      3 kinase (PI3K)-gamma-Akt pathway in this form of acute kidney injury. Using PI3K
      gamma knockout mice, we found that a conventional dose of cisplatin was more
      lethal in the knockout mice where the blood urea nitrogen and serum creatinine
      were significantly higher in them than in wild-type mice. Phosphorylation of Akt
      in the renal tubules was abrogated in the knockout mice with the severity of
      renal dysfunction and numbers of TUNEL (terminal deoxynucleotidyl transferase
      (TdT) mediated nick-end labeling)-positive renal tubule cells being higher in the
      knockout than in wild-type mice. Cisplatin treatment significantly increased.
      Caspase-3 activity, histone-associated DNA fragments, and number of annexin V
      positive cells was significantly higher in cisplatin-treated primary cultured
      renal tubular epithelial cells of knockout mice. Transfection of dominant-active
      forms of Akt and PI3K-gamma ameliorated apoptosis of the tubule epithelial cells
      derived from the knockout mice. Our results suggest that the PI3K-gamma-Akt
      pathway lessens apoptosis and plays a critical role in the maintenance of renal
      function in cisplatin-induced acute kidney injury.

PMID- 18046318
TI  - Effect of bolus and divided feeding on urine ions and supersaturation in genetic
      hypercalciuric stone-forming rats.
AB  - Because urine ion excretion varies throughout the day, clinicians monitor 24 h
      urine samples to measure ion excretion and supersaturation in kidney stone
      patients. However, these results are averages and may not reflect maximal
      supersaturation which drives stone formation. We measured ion excretion and
      saturation in genetic hypercalciuric stone-forming rats on both a normal or low
      calcium diet over 0-3, 3-6 and 6-24 h using two feeding protocols, where the
      daily food allotment was fed either as a bolus or divided into three portions.
      With a normal calcium diet, urine calcium, oxalate, volume, and calcium oxalate
      supersaturation were significantly greater on the bolus compared to the divided
      feeds in the prandial and postprandial periods. Bolus eaters also excreted more
      calcium and oxalate and had increased volume over 24 h. Maximal calcium oxalate
      supersaturation was greater during the initial time periods than during the
      entire 24 h, regardless of the feeding schedule. With the low calcium diet, the
      effect of bolus feeding was reduced. Thus, urine ion excretion and
      supersaturation vary with the type of feeding. If these results are confirmed in
      man, it suggests that eating as a bolus may result in greater prandial and
      postprandial calcium oxalate supersaturation. This may increase growth on
      Randall's plaques and promote stone disease.

PMID- 18046319
TI  - Exploring the biology of vascular calcification in chronic kidney disease: what's
      circulating?
AB  - Chronic kidney disease (CKD) is associated with fatal cardiovascular consequences
      in part due to ectopic calcification of soft tissues particularly arteries,
      capillaries, and cardiac valves. An increasing body of evidence from experimental
      studies and in vivo data suggest that (I) a mineral imbalance with
      hyperphosphatemia and high-circulating calcium x phosphate product, (II) a
      deficiency of systemic or local calcification inhibitors, (III) death or 'damage'
      of vascular smooth muscle cells (VSMCs), and/or (IV) phenotypic transformation of
      VSMCs to osteo/chondrocytic cells may all act in concert to initiate and sustain
      vascular calcification. In CKD patients inhibitory systems are overwhelmed by a
      multitude of agents that induce VSMC damage and cell death resulting in the
      release of vesicles capable of nucleating basic calcium phosphate. Studies with
      genetically altered mice have identified both local and systemic calcification
      inhibitors that act to maintain VSMC differentiation or regulate vesicle
      properties. However, for many of these proteins the mechanisms and sites of
      action are still under investigation. In particular, it is unclear whether
      factors present in the circulation have an inhibitory role there and whether
      circulating levels of these proteins influence or are indicative of underlying
      disease processes in individual patients. A greater understanding of the origins
      and roles of potential circulating inhibitors may result in novel strategies
      aimed at the prevention or reversal of the life-limiting calcifying
      vasculopathies seen in CKD patients.

PMID- 18046320
TI  - Expression and role of connexins in the rat renal vasculature.
AB  - Gap junctions are present in the juxtaglomerular apparatus enabling intercellular
      communication. Our study determined the location of different connexin subtypes
      within the juxtaglomerular apparatus of the rat, and the role of these subtypes
      in renal hemodynamics through the use of specific mimetic peptides.
      Immunohistochemical analysis showed connexins 37 and 40 expression in the
      endothelial and renin-secreting cells of the afferent arteriole, while connexin
      40 was also found in extra- and intraglomerular mesangial cells. In contrast,
      connexin 43 was weakly expressed in endothelial cells of the afferent arteriole
      and within the glomerulus. Intra-renal infusion of the peptides (GAP) reported to
      block specific gap junctions ((Cx37,43)GAP27 or (Cx40)GAP27), elevated blood
      pressure, plasma renin activity, and angiotensin II levels, while decreasing
      renal plasma flow without a significant change in the glomerular filtration rate.
      Subsequent restoration of blood pressure reduced both renal plasma flow and
      glomerular filtration rate. In contrast, (Cx43)GAP26 reduced glomerular
      filtration rate without alterations in blood pressure, renal plasma flow, plasma
      renin activity, or angiotensin II levels. Hence, connexins 37 and 40 are
      expressed in the rat juxtaglomerular apparatus and these proteins control, in
      part, the renin-angiotensin system and renal autoregulation.

PMID- 18046321
TI  - Risky business.

PMID- 18046324
TI  - Stalled polymerases and transcriptional regulation.

PMID- 18046325
TI  - Sudden and unexpected.

PMID- 18046326
TI  - High-maintenance proteins and hypertriglyceridemia.

PMID- 18046327
TI  - Two sides of the same coin.

PMID- 18046332
TI  - Initiation of zebrafish haematopoiesis by the TATA-box-binding protein-related
      factor Trf3.
AB  - TATA-box-binding protein (TBP)-related factor 3, TRF3 (also called TBP2), is a
      vertebrate-specific member of the TBP family that has a conserved carboxy
      terminal region and DNA-binding domain virtually identical to that of TBP (ref.
      1). TRF3 is highly expressed during embryonic development, and studies in
      zebrafish and Xenopus have shown that it is required for normal embryogenesis.
      Here we show that zebrafish embryos depleted of Trf3 exhibit multiple
      developmental defects and, in particular, fail to undergo haematopoiesis.
      Expression profiling for Trf3-dependent genes identified mespa, which encodes a
      transcription factor whose murine orthologue is required for mesoderm
      specification, and chromatin immunoprecipitation verified that Trf3 binds to the
      mespa promoter. Depletion of Mespa resulted in developmental and haematopoietic
      defects markedly similar to those induced by Trf3 depletion. Injection of mespa
      messenger RNA (mRNA) restored normal development to a Trf3-depleted embryo,
      indicating mespa is the single Trf3 target gene required for zebrafish
      embryogenesis. Zebrafish embryos depleted of Trf3 or Mespa also failed to express
      cdx4, a caudal-related gene required for haematopoiesis. Mespa binds to the cdx4
      promoter, and epistasis analysis revealed an ordered trf3-mespa-cdx4 pathway.
      Thus, in zebrafish, commitment of mesoderm to the haematopoietic lineage occurs
      through a transcription factor pathway initiated by a TBP-related factor.

PMID- 18046331
TI  - RNA-mediated epigenetic programming of a genome-rearrangement pathway.
AB  - Genome-wide DNA rearrangements occur in many eukaryotes but are most exaggerated
      in ciliates, making them ideal model systems for epigenetic phenomena. During
      development of the somatic macronucleus, Oxytricha trifallax destroys 95% of its
      germ line, severely fragmenting its chromosomes, and then unscrambles hundreds of
      thousands of remaining fragments by permutation or inversion. Here we demonstrate
      that DNA or RNA templates can orchestrate these genome rearrangements in
      Oxytricha, supporting an epigenetic model for sequence-dependent comparison
      between germline and somatic genomes. A complete RNA cache of the maternal
      somatic genome may be available at a specific stage during development to provide
      a template for correct and precise DNA rearrangement. We show the existence of
      maternal RNA templates that could guide DNA assembly, and that disruption of
      specific RNA molecules disables rearrangement of the corresponding gene.
      Injection of artificial templates reprogrammes the DNA rearrangement pathway,
      suggesting that RNA molecules guide genome rearrangement.

PMID- 18046334
TI  - The interplay between MYC and HIF in cancer.
AB  - The interaction of MYC and hypoxia inducible factors (HIFs) under physiological,
      non-tumorigenic conditions provides insights into normal homeostatic cellular
      responses to low oxygen levels (hypoxia). Many tumours contain genetic
      alterations, such as MYC activation, that can collaborate with HIF to confer
      metabolic advantages to tumour cells, which tend to exist in a hypoxic
      microenvironment. This Perspective emphasizes the differences between the
      transcriptional network that operates under normal homeostatic conditions and the
      network in a tumorigenic milieu.

PMID- 18046333
TI  - Distinct physiological states of Plasmodium falciparum in malaria-infected
      patients.
AB  - Infection with the malaria parasite Plasmodium falciparum leads to widely
      different clinical conditions in children, ranging from mild flu-like symptoms to
      coma and death. Despite the immense medical implications, the genetic and
      molecular basis of this diversity remains largely unknown. Studies of in vitro
      gene expression have found few transcriptional differences between different
      parasite strains. Here we present a large study of in vivo expression profiles of
      parasites derived directly from blood samples from infected patients. The in vivo
      expression profiles define three distinct transcriptional states. The biological
      basis of these states can be interpreted by comparison with an extensive
      compendium of expression data in the yeast Saccharomyces cerevisiae. The three
      states in vivo closely resemble, first, active growth based on glycolytic
      metabolism, second, a starvation response accompanied by metabolism of
      alternative carbon sources, and third, an environmental stress response. The
      glycolytic state is highly similar to the known profile of the ring stage in
      vitro, but the other states have not been observed in vitro. The results reveal a
      previously unknown physiological diversity in the in vivo biology of the malaria
      parasite, in particular evidence for a functional mitochondrion in the asexual
      stage parasite, and indicate in vivo and in vitro studies to determine how this
      variation may affect disease manifestations and treatment.

PMID- 18046335
TI  - Relaxant effects of an alkaloid-rich fraction from Aspidosperma ulei root bark on
      isolated rabbit corpus cavernosum.
AB  - We described earlier that an alkaloid-rich fraction (F(3-5)) from Aspidosperma
      ulei (Markgr) induces penile erection-like behavioral responses in mice. This
      study verified a possible relaxant effect of this fraction on isolated rabbit
      corpus cavernosum (RbCC) strips precontracted by phenylephrine (1 microM) or K+
      60 mM. F(3-5) (1-300 microg ml(-1)) relaxed the RbCC strips in a concentration
      dependent and reversible manner. The relaxant effect of F(3-5) (100 microg ml(
      1)) on phenylephrine contraction was unaffected in the presence of atropine, N
      omega-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1
      one and by preincubation with tetrodotoxin, glibenclamide, apamine and
      charybdotoxin suggesting that mechanisms other than cholinergic, nitrergic, sGC
      activation or potassium channel opening are probably involved. However, the
      phasic component of the contraction induced by K+ 60 mM as well as the maximal
      contraction elicited by increasing external Ca2+ concentrations in depolarized
      corpora cavernosa was inhibited by F(3-5). We conclude that F(3-5) relaxes the
      RbCC smooth muscle, at least in part, through a blockade of calcium influx or its
      function.

PMID- 18046336
TI  - Predictors of mortality and length of stay for neonates admitted to children's
      hospital neonatal intensive care units.
AB  - OBJECTIVE: Current scoring systems, which adjust prediction for severity of
      illness, do not account for higher observed mortality in neonatal intensive care
      units (NICUs) of children's hospitals than that of perinatal centers. We
      hypothesized that three potential predictors, (a) admission from another NICU,
      (b) presence of congenital anomalies and (c) need for surgery, would modify
      expected mortality and/or length of stay for infants admitted to NICUs in
      children's hospitals. STUDY DESIGN: We reviewed consecutive admissions to two
      NICUs in children's hospitals in Canada. We performed regression analyses to
      evaluate these potential predictors and severity-of-illness indices for the
      outcomes of mortality and length of stay. RESULT: Of 625 neonatal admissions,
      transfer from another NICU, congenital anomalies requiring admission and surgery
      were identified in 371 (59%). Using logistic regression, mortality was predicted
      based on admission from another NICU (odds ratio (OR) 1.92; 95% confidence
      interval (CI) 1.04, 3.57), congenital anomalies (OR 7.28; 95% CI 3.69, 14.36) and
      a validated severity-of-illness score, the Score for Neonatal Acute Physiology
      Perinatal Extension Version II (SNAPPE-II; OR 1.07; 95% CI 1.05, 1.09 per point).
      By contrast, surgical intervention was predictive of survival (OR 0.35; 95% CI
      0.18, 0.67). Length of stay >or=21 days was predicted by SNAPPE-II (OR 1.02; 95%
      CI 1.01, 1.03 per point), congenital anomalies (OR 2.47; 95% CI 1.60, 3.79) and
      surgery (OR 2.73; 95% CI 1.77, 4.21). CONCLUSION: Fair performance comparisons of
      NICUs with different case-mixes, such as children's hospital and perinatal NICUs,
      in addition to severity-of-illness indices, should account for admissions from
      another NICU, congenital anomalies and surgery.

PMID- 18046337
TI  - Fluid regimens in the first week of life may increase risk of patent ductus
      arteriosus in extremely low birth weight infants.
AB  - BACKGROUND: High fluid volumes may increase neonatal morbidity. However, evidence
      supporting fluid restriction is inconclusive and restricting fluids may restrict
      caloric intake. OBJECTIVE: To determine if higher fluid intake was associated
      with increased risk of patent ductus arteriosus (PDA) or bronchopulmonary
      dysplasia (BPD) in extremely low birth weight (ELBW) infants. STUDY DESIGN: A
      total of 204 ELBW (<or=32 weeks, <or=1250 g) infant survivors were grouped into
      low-, intermediate- and high-fluid groups. chi2 analyzed proportions of subjects
      with and without morbidities across groups. Logistic regression quantified
      increased risk of PDA or BPD associated with fluid intake while controlling for
      confounders. Analysis of variance compared differences in caloric intake across
      groups. RESULT: After controlling for gestational age, severity of illness and
      weight change, fluid intake on day 2 (odds ratio (OR) 1.014; confidence interval
      (CI) 1.001 to 1.028) and day 3 (OR 1.022; CI 1.004 to 1.040) was associated with
      increased risk of PDA. CONCLUSION: High fluid intake (>170 ml kg(-1) day(-1)) in
      the first days of life is associated with increased risk of PDA.

PMID- 18046338
TI  - Systemic fungal infection is associated with the development of retinopathy of
      prematurity in very low birth weight infants: a meta-review.
AB  - OBJECTIVE: To study the association between systemic fungal infection (SFI) and
      the development of retinopathy of prematurity (ROP) and severe ROP in very low
      birth weight (VLBW) infants by systematic review and meta-analysis. STUDY DESIGN:
      A meta-review was performed using a fixed effects model. The exposure and
      outcomes studied were SFI and all ROP/severe ROP, respectively in VLBW infants.
      Results and effect sizes analyzed with Review Manager 4.2 software are expressed
      as relative risk (RR), odds ratio (OR), risk difference (RD) and number needed to
      harm (NNH) with 95% confidence intervals. RESULT: Data for severe ROP were
      available from eight studies and on all ROP from seven of those eight studies.
      Estimated gestational age ranged from 24.7+/-1.6 to 28.6+/-4 weeks and birth
      weight from 673 (median) (range 426 to 995) to 1108+/-266 g (mean+/-s.d.). A
      total of 261 of 303 babies with SFI had all ROP vs 1081 of 1648 babies without
      SFI (OR 3.4(*), 2.34-4.95) and 118 of 330 babies with SFI had severe ROP vs 235
      of 1951 babies without SFI (OR 4.06(*), 3.05-5.42). The NNH was 5.56(*) (4.54
      7.14) for all ROP and 4.54(*) (3.70 to 5.88) for severe ROP ((*) P<0.00001).
      CONCLUSION: SFIs are associated with the development of all degrees of ROP and
      severe ROP in VLBW infants.

PMID- 18046339
TI  - Choice of antenatal testing significantly effects a patient's work obligations.
AB  - OBJECTIVE: We sought to compare two approaches to antenatal testing for their
      impact on the workforce. STUDY DESIGN: This is a prospective observational study
      of women who presented for antenatal testing. All women were given a survey upon
      presentation. As per hospital protocol, nonstress testing (NST) was performed
      semiweekly and biophysical profile (BPP) was performed weekly. The choice of
      testing was determined by the attending physician. chi2- and Student's t-tests
      were performed where appropriate. A P-value of <0.05 was considered significant.
      RESULT: A total of 195 women were surveyed. Among them, 94 women had an NST and
      101 had a BPP. Overall, 59.2% were multiparous, 33.1% had to arrange for child
      care and 97.2% felt reassured by the testing. There were no differences in
      demographic characteristics, education, type of insurance or employment status
      between the groups. Women who had NSTs were more likely to lose time from work
      than those who had BPPs (218.4 versus 68.9 min; P<0.001). Of the women who had
      semiweekly NSTs, 80.6% would have preferred weekly testing. If the 94 women who
      received semiweekly testing had weekly testing, a total of 534.4 h would have
      been available for the workforce. CONCLUSION: Twice-weekly NST results in a
      significant increase in time lost from the workforce compared with weekly BPP.

PMID- 18046340
TI  - Amnioinfusion in preterm PROM: effects on amnion and cord histology.
AB  - OBJECTIVE: To investigate the effects of transabdominal amnioinfusion (TA) on the
      histology of amnion (A) and umbilical cord (UC). STUDY DESIGN: From a cohort of
      56 singleton pregnancies with premature rupture of membranes (PROM) at <or=24.6
      weeks, we excluded those who did not develop severe oligohydramnios (n=12). Of
      the 44 patients, 29 consented to TA and 15 declined the procedure. TA was
      performed with normal saline solution. RESULT: Women who consented to TA
      underwent a median of three procedures had a gestational age at PROM of 18.7
      weeks and at delivery of 26.1 weeks, with a latency of 50 days. Compared with
      subjects who declined the procedure, TA had a beneficial effect on clinical
      variables, mediated primarily by a longer latency. TA was not associated with
      identifiable effects on the histologic features of A or UC. CONCLUSION: A and UC
      histology is not significantly affected by exposure to saline solution even for
      prolonged periods of time.

PMID- 18046341
TI  - Identification of candidate genes that influence sex hormone-dependent disease
      phenotypes in mouse lupus.
AB  - Ninety percent of systemic lupus erythematosus patients are female, and gender
      differences in lupus susceptibility are also observed in (New Zealand Black x New
      Zealand White)F1 (BWF1) lupus-prone mice. We followed orchiectomized, intact male
      and female BWF1 mice for lupus-like disease for 1 year. A comparative gene
      expression analysis was then used to identify candidate genes potentially
      responsible for gender-dependent differences in lupus susceptibility. Seven genes
      encoded on the sex chromosomes and 77 probe sets, including 14 immunoglobulin
      genes, encoded on the autosomal chromosomes were identified as differentially
      expressed in male versus female BWF1 splenocytes prior to disease onset. Five
      genes were determined to be regulated by either estradiol or dihydrotestosterone
      in an in vivo system and most of them were preferentially expressed in antigen
      presenting cells. Gender differences in the expression of Csf3-r, Histh1c,
      Serpinb2, Slc6a4 and Cd22 in BWF1 mice are the result of transcriptional
      modification by sex hormones and warrant further investigation. The
      identification of candidate genes and their expression patterns in splenocyte sub
      populations provide new information regarding the mechanisms by which sex
      hormones influence the development of mouse lupus.

PMID- 18046347
TI  - An inconvenient truth.

PMID- 18046342
TI  - Ediacaran oxidation and biotic evolution.
AB  - The link between the radiation of various lineages of eukaryotes in the latest
      Proterozoic and massive environmental changes--oxygenation, global ice ages and
      bolide impact--is the focus of much research interest. Fike et al. use carbon and
      sulphur isotope-chemostratigraphic data from Oman to propose three stages of
      oxidation in the Ediacaran oceans, and link the second and third stages to
      eukaryote diversification. The second stage, signalled by strongly 13C-depleted
      sedimentary carbonates (the 'Shuram excursion'), is believed to result from
      oxidation of a large, deep-ocean reservoir of organic carbon. Fike et al. use our
      data to assert that a correlative carbon isotope excursion in Australia coincided
      with the initial diversification of acanthomorphic acritarchs. Peak diversity is
      claimed to have coincided with subsequent deposition of 13C-enriched carbonate
      and the third oxidation stage. However, the authors seem to have misinterpreted
      our data, which instead indicate that diversification significantly preceded the
      Shuram excursion; this weakens their argument for a link between the inferred
      oxidation events and eukaryote evolution.

PMID- 18046348
TI  - The paradox of Pakistan.

PMID- 18046349
TI  - The big picture.

PMID- 18046352
TI  - Deforestation on the agenda at climate meeting?

PMID- 18046353
TI  - Loopholes in oversight rules revealed.

PMID- 18046354
TI  - Now in Arabic... Science classics get translated.

PMID- 18046355
TI  - Brazil to boost science spend.

PMID- 18046357
TI  - Europe looks to draw power from Africa.

PMID- 18046356
TI  - Monuments and instruments.

PMID- 18046358
TI  - Plant-disease controls sap outbreak responses.

PMID- 18046360
TI  - Graphic detail: the real value of a scientist's wage.

PMID- 18046368
TI  - Fever pitch.

PMID- 18046373
TI  - Age research: a new angle on 'old'.

PMID- 18046374
TI  - Space and astronomy: the girl next door.

PMID- 18046375
TI  - Good thinking should not be wasted on bad ideas.

PMID- 18046376
TI  - Modifying theories is the fabric of scientific progress.

PMID- 18046377
TI  - Moon is the best witness to early Solar System history.

PMID- 18046378
TI  - Each co-author should sign to reduce risk of fraud.

PMID- 18046384
TI  - The ethical regulation of science.

PMID- 18046385
TI  - Venus: express dispatches.

PMID- 18046386
TI  - Reproduction: the unusual suspect.

PMID- 18046388
TI  - Cell biology: pore puzzle.

PMID- 18046389
TI  - Microscopy: elementary resolution.

PMID- 18046390
TI  - Neuroscience: sensors and synchronicity.

PMID- 18046391
TI  - Molecular motors: a step dissected.

PMID- 18046392
TI  - Obituary: Leslie Orgel (1927-2007).

PMID- 18046393
TI  - Venus as a more Earth-like planet.
AB  - Venus is Earth's near twin in mass and radius, and our nearest planetary
      neighbour, yet conditions there are very different in many respects. Its
      atmosphere, mostly composed of carbon dioxide, has a surface temperature and
      pressure far higher than those of Earth. Only traces of water are found, although
      it is likely that there was much more present in the past, possibly forming Earth
      like oceans. Here we discuss how the first year of observations by Venus Express
      brings into focus the evolutionary paths by which the climates of two similar
      planets diverged from common beginnings to such extremes. These include a CO2
      driven greenhouse effect, erosion of the atmosphere by solar particles and
      radiation, surface-atmosphere interactions, and atmospheric circulation regimes
      defined by differing planetary rotation rates.

PMID- 18046394
TI  - Morphology and dynamics of the upper cloud layer of Venus.
AB  - Venus is completely covered by a thick cloud layer, of which the upper part is
      composed of sulphuric acid and some unknown aerosols. The cloud tops are in fast
      retrograde rotation (super-rotation), but the factors responsible for this super
      rotation are unknown. Here we report observations of Venus with the Venus
      Monitoring Camera on board the Venus Express spacecraft. We investigate both
      global and small-scale properties of the clouds, their temporal and latitudinal
      variations, and derive wind velocities. The southern polar region is highly
      variable and can change dramatically on timescales as short as one day, perhaps
      arising from the injection of SO2 into the mesosphere. The convective cells in
      the vicinity of the subsolar point are much smaller than previously inferred,
      which we interpret as indicating that they are confined to the upper cloud layer,
      contrary to previous conclusions, but consistent with more recent study.

PMID- 18046395
TI  - South-polar features on Venus similar to those near the north pole.
AB  - Venus has no seasons, slow rotation and a very massive atmosphere, which is
      mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared
      observations by previous missions to Venus revealed a bright 'dipole' feature
      surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double
      eye' feature at the centre of a vast vortex that rotates around the pole, and is
      possibly associated with rapid downwelling. The polar cold collar is a wide,
      shallow river of cold air that circulates around the polar vortex. One
      outstanding question has been whether the global circulation was symmetric, such
      that a dipole feature existed at the south pole. Here we report observations of
      Venus' south-polar region, where we have seen clouds with morphology much like
      those around the north pole, but rotating somewhat faster than the northern
      dipole. The vortex may extend down to the lower cloud layers that lie at about 50
      km height and perhaps deeper. The spectroscopic properties of the clouds around
      the south pole are compatible with a sulphuric acid composition.

PMID- 18046397
TI  - A warm layer in Venus' cryosphere and high-altitude measurements of HF, HCl, H2O
      and HDO.
AB  - Venus has thick clouds of H2SO4 aerosol particles extending from altitudes of 40
      to 60 km. The 60-100 km region (the mesosphere) is a transition region between
      the 4 day retrograde superrotation at the top of the thick clouds and the solar
      antisolar circulation in the thermosphere (above 100 km), which has upwelling
      over the subsolar point and transport to the nightside. The mesosphere has a
      light haze of variable optical thickness, with CO, SO2, HCl, HF, H2O and HDO as
      the most important minor gaseous constituents, but the vertical distribution of
      the haze and molecules is poorly known because previous descent probes began
      their measurements at or below 60 km. Here we report the detection of an
      extensive layer of warm air at altitudes 90-120 km on the night side that we
      interpret as the result of adiabatic heating during air subsidence. Such a strong
      temperature inversion was not expected, because the night side of Venus was
      otherwise so cold that it was named the 'cryosphere' above 100 km. We also
      measured the mesospheric distributions of HF, HCl, H2O and HDO. HCl is less
      abundant than reported 40 years ago. HDO/H2O is enhanced by a factor of
      approximately 2.5 with respect to the lower atmosphere, and there is a general
      depletion of H2O around 80-90 km for which we have no explanation.

PMID- 18046398
TI  - The loss of ions from Venus through the plasma wake.
AB  - Venus, unlike Earth, is an extremely dry planet although both began with similar
      masses, distances from the Sun, and presumably water inventories. The high
      deuterium-to-hydrogen ratio in the venusian atmosphere relative to Earth's also
      indicates that the atmosphere has undergone significantly different evolution
      over the age of the Solar System. Present-day thermal escape is low for all
      atmospheric species. However, hydrogen can escape by means of collisions with hot
      atoms from ionospheric photochemistry, and although the bulk of O and O2 are
      gravitationally bound, heavy ions have been observed to escape through
      interaction with the solar wind. Nevertheless, their relative rates of escape,
      spatial distribution, and composition could not be determined from these previous
      measurements. Here we report Venus Express measurements showing that the dominant
      escaping ions are O+, He+ and H+. The escaping ions leave Venus through the
      plasma sheet (a central portion of the plasma wake) and in a boundary layer of
      the induced magnetosphere. The escape rate ratios are Q(H+)/Q(O+) = 1.9;
      Q(He+)/Q(O+) = 0.07. The first of these implies that the escape of H+ and O+,
      together with the estimated escape of neutral hydrogen and oxygen, currently
      takes place near the stoichometric ratio corresponding to water.

PMID- 18046396
TI  - A dynamic upper atmosphere of Venus as revealed by VIRTIS on Venus Express.
AB  - The upper atmosphere of a planet is a transition region in which energy is
      transferred between the deeper atmosphere and outer space. Molecular emissions
      from the upper atmosphere (90-120 km altitude) of Venus can be used to
      investigate the energetics and to trace the circulation of this hitherto little
      studied region. Previous spacecraft and ground-based observations of infrared
      emission from CO2, O2 and NO have established that photochemical and dynamic
      activity controls the structure of the upper atmosphere of Venus. These data,
      however, have left unresolved the precise altitude of the emission owing to a
      lack of data and of an adequate observing geometry. Here we report measurements
      of day-side CO2 non-local thermodynamic equilibrium emission at 4.3 microm,
      extending from 90 to 120 km altitude, and of night-side O2 emission extending
      from 95 to 100 km. The CO2 emission peak occurs at approximately 115 km and
      varies with solar zenith angle over a range of approximately 10 km. This confirms
      previous modelling, and permits the beginning of a systematic study of the
      variability of the emission. The O2 peak emission happens at 96 km +/- 1 km,
      which is consistent with three-body recombination of oxygen atoms transported
      from the day side by a global thermospheric sub-solar to anti-solar circulation,
      as previously predicted.

PMID- 18046399
TI  - Little or no solar wind enters Venus' atmosphere at solar minimum.
AB  - Venus has no significant internal magnetic field, which allows the solar wind to
      interact directly with its atmosphere. A field is induced in this interaction,
      which partially shields the atmosphere, but we have no knowledge of how effective
      that shield is at solar minimum. (Our current knowledge of the solar wind
      interaction with Venus is derived from measurements at solar maximum.) The bow
      shock is close to the planet, meaning that it is possible that some solar wind
      could be absorbed by the atmosphere and contribute to the evolution of the
      atmosphere. Here we report magnetic field measurements from the Venus Express
      spacecraft in the plasma environment surrounding Venus. The bow shock under low
      solar activity conditions seems to be in the position that would be expected from
      a complete deflection by a magnetized ionosphere. Therefore little solar wind
      enters the Venus ionosphere even at solar minimum.

PMID- 18046400
TI  - The structure of Venus' middle atmosphere and ionosphere.
AB  - The atmosphere and ionosphere of Venus have been studied in the past by
      spacecraft with remote sensing or in situ techniques. These early missions,
      however, have left us with questions about, for example, the atmospheric
      structure in the transition region from the upper troposphere to the lower
      mesosphere (50-90 km) and the remarkably variable structure of the ionosphere.
      Observations become increasingly difficult within and below the global cloud deck
      (<50 km altitude), where strong absorption greatly limits the available
      investigative spectrum to a few infrared windows and the radio range. Here we
      report radio-sounding results from the first Venus Express Radio Science (VeRa)
      occultation season. We determine the fine structure in temperatures at upper
      cloud-deck altitudes, detect a distinct day-night temperature difference in the
      southern middle atmosphere, and track day-to-day changes in Venus' ionosphere.

PMID- 18046401
TI  - Lightning on Venus inferred from whistler-mode waves in the ionosphere.
AB  - The occurrence of lightning in a planetary atmosphere enables chemical processes
      to take place that would not occur under standard temperatures and pressures.
      Although much evidence has been reported for lightning on Venus, some searches
      have been negative and the existence of lightning has remained controversial. A
      definitive detection would be the confirmation of electromagnetic, whistler-mode
      waves propagating from the atmosphere to the ionosphere. Here we report
      observations of Venus' ionosphere that reveal strong, circularly polarized,
      electromagnetic waves with frequencies near 100 Hz. The waves appear as bursts of
      radiation lasting 0.25 to 0.5 s, and have the expected properties of whistler
      mode signals generated by lightning discharges in Venus' clouds.

PMID- 18046402
TI  - Protein translocation across the eukaryotic endoplasmic reticulum and bacterial
      plasma membranes.
AB  - A decisive step in the biosynthesis of many proteins is their partial or complete
      translocation across the eukaryotic endoplasmic reticulum membrane or the
      prokaryotic plasma membrane. Most of these proteins are translocated through a
      protein-conducting channel that is formed by a conserved, heterotrimeric membrane
      protein complex, the Sec61 or SecY complex. Depending on channel binding
      partners, polypeptides are moved by different mechanisms: the polypeptide chain
      is transferred directly into the channel by the translating ribosome, a
      ratcheting mechanism is used by the endoplasmic reticulum chaperone BiP, and a
      pushing mechanism is used by the bacterial ATPase SecA. Structural, genetic and
      biochemical data show how the channel opens across the membrane, releases
      hydrophobic segments of membrane proteins laterally into lipid, and maintains the
      membrane barrier for small molecules.

PMID- 18046403
TI  - Shiga toxin induces tubular membrane invaginations for its uptake into cells.
AB  - Clathrin seems to be dispensable for some endocytic processes and, in several
      instances, no cytosolic coat protein complexes could be detected at sites of
      membrane invagination. Hence, new principles must in these cases be invoked to
      account for the mechanical force driving membrane shape changes. Here we show
      that the Gb3 (glycolipid)-binding B-subunit of bacterial Shiga toxin induces
      narrow tubular membrane invaginations in human and mouse cells and model
      membranes. In cells, tubule occurrence increases on energy depletion and
      inhibition of dynamin or actin functions. Our data thus demonstrate that active
      cellular processes are needed for tubule scission rather than tubule formation.
      We conclude that the B-subunit induces lipid reorganization that favours negative
      membrane curvature, which drives the formation of inward membrane tubules. Our
      findings support a model in which the lateral growth of B-subunit-Gb3
      microdomains is limited by the invagination process, which itself is regulated by
      membrane tension. The physical principles underlying this basic cargo-induced
      membrane uptake may also be relevant to other internalization processes, creating
      a rationale for conceptualizing the perplexing diversity of endocytic routes.

PMID- 18046404
TI  - A dual-Ca2+-sensor model for neurotransmitter release in a central synapse.
AB  - Ca2+-triggered synchronous neurotransmitter release is well described, but
      asynchronous release-in fact, its very existence-remains enigmatic. Here we
      report a quantitative description of asynchronous neurotransmitter release in
      calyx-of-Held synapses. We show that deletion of synaptotagmin 2 (Syt2) in mice
      selectively abolishes synchronous release, allowing us to study pure asynchronous
      release in isolation. Using photolysis experiments of caged Ca2+, we demonstrate
      that asynchronous release displays a Ca2+ cooperativity of approximately 2 with a
      Ca2+ affinity of approximately 44 microM, in contrast to synchronous release,
      which exhibits a Ca2+ cooperativity of approximately 5 with a Ca2+ affinity of
      approximately 38 muM. Our results reveal that release triggered in wild-type
      synapses at low Ca2+ concentrations is physiologically asynchronous, and that
      asynchronous release completely empties the readily releasable pool of vesicles
      during sustained elevations of Ca2+. We propose a dual-Ca2+-sensor model of
      release that quantitatively describes the contributions of synchronous and
      asynchronous release under conditions of different presynaptic Ca2+ dynamics.

PMID- 18046405
TI  - Determining the architectures of macromolecular assemblies.
AB  - To understand the workings of a living cell, we need to know the architectures of
      its macromolecular assemblies. Here we show how proteomic data can be used to
      determine such structures. The process involves the collection of sufficient and
      diverse high-quality data, translation of these data into spatial restraints, and
      an optimization that uses the restraints to generate an ensemble of structures
      consistent with the data. Analysis of the ensemble produces a detailed
      architectural map of the assembly. We developed our approach on a challenging
      model system, the nuclear pore complex (NPC). The NPC acts as a dynamic barrier,
      controlling access to and from the nucleus, and in yeast is a 50 MDa assembly of
      456 proteins. The resulting structure, presented in an accompanying paper,
      reveals the configuration of the proteins in the NPC, providing insights into its
      evolution and architectural principles. The present approach should be applicable
      to many other macromolecular assemblies.

PMID- 18046406
TI  - The molecular architecture of the nuclear pore complex.
AB  - Nuclear pore complexes (NPCs) are proteinaceous assemblies of approximately 50
      MDa that selectively transport cargoes across the nuclear envelope. To determine
      the molecular architecture of the yeast NPC, we collected a diverse set of
      biophysical and proteomic data, and developed a method for using these data to
      localize the NPC's 456 constituent proteins (see the accompanying paper). Our
      structure reveals that half of the NPC is made up of a core scaffold, which is
      structurally analogous to vesicle-coating complexes. This scaffold forms an
      interlaced network that coats the entire curved surface of the nuclear envelope
      membrane within which the NPC is embedded. The selective barrier for transport is
      formed by large numbers of proteins with disordered regions that line the inner
      face of the scaffold. The NPC consists of only a few structural modules that
      resemble each other in terms of the configuration of their homologous
      constituents, the most striking of these being a 16-fold repetition of 'columns'.
      These findings provide clues to the evolutionary origins of the NPC.

PMID- 18046407
TI  - Visualizing single-molecule diffusion in mesoporous materials.
AB  - Periodic mesoporous materials formed through the cooperative self-assembly of
      surfactants and framework building blocks can assume a variety of structures, and
      their widely tuneable properties make them attractive hosts for numerous
      applications. Because the molecular movement in the pore system is the most
      important and defining characteristic of porous materials, it is of interest to
      learn about this behaviour as a function of local structure. Generally,
      individual fluorescent dye molecules can be used as molecular beacons with which
      to explore the structure of--and the dynamics within--these porous hosts, and
      single-molecule fluorescence techniques provide detailed insights into the
      dynamics of various processes, ranging from biology to heterogeneous catalysis.
      However, optical microscopy methods cannot directly image the mesoporous
      structure of the host system accommodating the diffusing molecules, whereas
      transmission electron microscopy provides detailed images of the porous
      structure, but no dynamic information. It has therefore not been possible to
      'see' how molecules diffuse in a real nanoscale pore structure. Here we present a
      combination of electron microscopic mapping and optical single-molecule tracking
      experiments to reveal how a single luminescent dye molecule travels through
      linear or strongly curved sections of a mesoporous channel system. In our
      approach we directly correlate porous structures detected by transmission
      electron microscopy with the diffusion dynamics of single molecules detected by
      optical microscopy. This opens up new ways of understanding the interactions of
      host and guest.

PMID- 18046408
TI  - A diffusion mechanism for core-mantle interaction.
AB  - Understanding the geochemical behaviour of the siderophile elements--those
      tending to form alloys with iron in natural environments--is important in the
      search for a deep-mantle chemical 'fingerprint' in upper mantle rocks, and also
      in the evaluation of models of large-scale differentiation of the Earth and
      terrestrial planets. These elements are highly concentrated in the core relative
      to the silicate mantle, but their concentrations in upper mantle rocks are higher
      than predicted by most core-formation models. It has been suggested that mixing
      of outer-core material back into the mantle following core formation may be
      responsible for the siderophile element ratios observed in upper mantle rocks.
      Such re-mixing has been attributed to an unspecified metal-silicate interaction
      in the reactive D'' layer just above the core-mantle boundary. The siderophile
      elements are excellent candidates as indicators of an outer-core contribution to
      the mantle, but the nature and existence of possible core-mantle interactions is
      controversial. In light of the recent findings that grain-boundary diffusion of
      oxygen through a dry intergranular medium may be effective over geologically
      significant length scales and that grain boundaries can be primary storage sites
      for incompatible lithophile elements, the question arises as to whether
      siderophile elements might exhibit similar (or greater) grain-boundary mobility.
      Here we report experimental results from a study of grain-boundary diffusion of
      siderophile elements through polycrystalline MgO that were obtained by
      quantifying the extent of alloy formation between initially pure metals separated
      by approximately 1 mm of polycrystalline MgO. Grain-boundary diffusion resulted
      in significant alloying of sink and source particles, enabling calculation of
      grain-boundary fluxes. Our computed diffusivities were high enough to allow
      transport of a number of siderophile elements over geologically significant
      length scales (tens of kilometres) over the age of the Earth. This finding
      establishes grain-boundary diffusion as a potential fast pathway for chemical
      communication between the core and mantle.

PMID- 18046409
TI  - Small molecule activators of SIRT1 as therapeutics for the treatment of type 2
      diabetes.
AB  - Calorie restriction extends lifespan and produces a metabolic profile desirable
      for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent
      deacetylase, is a principal modulator of pathways downstream of calorie
      restriction that produce beneficial effects on glucose homeostasis and insulin
      sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing
      effects of calorie restriction in lower organisms and in mice fed a high-fat diet
      ameliorates insulin resistance, increases mitochondrial content, and prolongs
      survival. Here we describe the identification and characterization of small
      molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold
      more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide
      substrate complex at an allosteric site amino-terminal to the catalytic domain
      and lower the Michaelis constant for acetylated substrates. In diet-induced obese
      and genetically obese mice, these compounds improve insulin sensitivity, lower
      plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats,
      hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators
      improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue,
      skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic
      approach for treating diseases of ageing such as type 2 diabetes.

PMID- 18046410
TI  - Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation
      mechanism.
AB  - Morphogens act in developing tissues to control the spatial arrangement of
      cellular differentiation. The activity of a morphogen has generally been viewed
      as a concentration-dependent response to a diffusible signal, but the duration of
      morphogen signalling can also affect cellular responses. One such example is the
      morphogen sonic hedgehog (SHH). In the vertebrate central nervous system and
      limbs, the pattern of cellular differentiation is controlled by both the amount
      and the time of SHH exposure. How these two parameters are interpreted at a
      cellular level has been unclear. Here we provide evidence that changing the
      concentration or duration of SHH has an equivalent effect on intracellular
      signalling. Chick neural cells convert different concentrations of SHH into time
      limited periods of signal transduction, such that signal duration is proportional
      to SHH concentration. This depends on the gradual desensitization of cells to
      ongoing SHH exposure, mediated by the SHH-dependent upregulation of patched 1
      (PTC1), a ligand-binding inhibitor of SHH signalling. Thus, in addition to its
      role in shaping the SHH gradient, PTC1 participates cell autonomously in gradient
      sensing. Together, the data reveal a novel strategy for morphogen interpretation,
      in which the temporal adaptation of cells to a morphogen integrates the
      concentration and duration of a signal to control differential gene expression.

PMID- 18046411
TI  - p53 regulates maternal reproduction through LIF.
AB  - Extensive studies have shown that p53 is important in tumour prevention. However,
      little is known about its normal physiological function. Here we show that p53 is
      important in reproduction, in a gender-specific manner. Significant decreases in
      embryonic implantation, pregnancy rate and litter size were observed in matings
      with p53-/- female mice but not with p53-/- male mice. The gene encoding
      leukaemia inhibitory factor (LIF), a cytokine critical for implantation, was
      identified as a p53-regulated gene that functions as the downstream mediator of
      this effect. p53 can regulate both basal and inducible transcription of LIF. Loss
      of p53 decreased both the level and function of LIF in uteri. Lower LIF levels
      were observed in the uteri of p53-/- mice than in those of p53+/+ mice,
      particularly at day 4 of pregnancy, when transiently induced high levels of LIF
      were crucial for embryonic implantation. This observation probably accounts for
      the impaired implantation of embryos in p53-/- female mice. Administration of LIF
      to pregnant p53-/- mice restored maternal reproduction by improving implantation.
      These results demonstrate a function for p53 in maternal reproduction through the
      regulation of LIF. Evidence is accumulating that p53 may have a similar function
      in humans.

PMID- 18046412
TI  - Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1.
AB  - With the emergence of multidrug resistant (MDR) bacteria, it is imperative to
      develop new intervention strategies. Current antibiotics typically target
      pathogen rather than host-specific biochemical pathways. Here we have developed
      kinase inhibitors that prevent intracellular growth of unrelated pathogens such
      as Salmonella typhimurium and Mycobacterium tuberculosis. An RNA interference
      screen of the human kinome using automated microscopy revealed several host
      kinases capable of inhibiting intracellular growth of S. typhimurium. The kinases
      identified clustered in one network around AKT1 (also known as PKB). Inhibitors
      of AKT1 prevent intracellular growth of various bacteria including MDR-M.
      tuberculosis. AKT1 is activated by the S. typhimurium effector SopB, which
      promotes intracellular survival by controlling actin dynamics through PAK4, and
      phagosome-lysosome fusion through the AS160 (also known as TBC1D4)-RAB14 pathway.
      AKT1 inhibitors counteract the bacterial manipulation of host signalling
      processes, thus controlling intracellular growth of bacteria. By using a
      reciprocal chemical genetics approach, we identified kinase inhibitors with
      antibiotic properties and their host targets, and we determined host signalling
      networks that are activated by intracellular bacteria for survival.

PMID- 18046413
TI  - Calcineurin sets the bandwidth for discrimination of signals during thymocyte
      development.
AB  - At critical times in development, cells are able to convert graded signals into
      discrete developmental outcomes; however, the mechanisms involved are poorly
      understood. During thymocyte development, cell fate is determined by signals
      originating from the alphabeta T-cell receptor. Low-affinity/avidity interactions
      between the T-cell receptor and peptide-MHC complexes direct differentiation to
      the single-positive stage (positive selection), whereas high-affinity/avidity
      interactions induce death by apoptosis (negative selection). Here we show that
      mice deficient in both calcineurin and nuclear factor of activated T cells
      (NFAT)c2/c3 lack a population of preselection thymocytes with enhanced ability to
      activate the mitogen-activated protein kinase (Raf-MEK-ERK) pathway, and fail to
      undergo positive selection. This defect can be partially rescued with
      constitutively active Raf, indicating that calcineurin controls MAPK signalling.
      Analysis of mice deficient in both Bim (which is required for negative selection)
      and calcineurin revealed that calcineurin-induced ERK (extracellular signal
      regulated kinase) sensitization is required for differentiation in response to
      'weak' positive selecting signals but not in response to 'strong' negative
      selecting signals (which normally induce apoptosis). These results indicate that
      early calcineurin/NFAT signalling produces a developmental period of ERK
      hypersensitivity, allowing very weak signals to induce positive selection. This
      mechanism might be generally useful in the discrimination of graded signals that
      induce different cell fates.

PMID- 18046414
TI  - mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha
      transcriptional complex.
AB  - Transcriptional complexes that contain peroxisome-proliferator-activated receptor
      coactivator (PGC)-1alpha control mitochondrial oxidative function to maintain
      energy homeostasis in response to nutrient and hormonal signals. An important
      component in the energy and nutrient pathways is mammalian target of rapamycin
      (mTOR), a kinase that regulates cell growth, size and survival. However, it is
      unknown whether and how mTOR controls mitochondrial oxidative activities. Here we
      show that mTOR is necessary for the maintenance of mitochondrial oxidative
      function. In skeletal muscle tissues and cells, the mTOR inhibitor rapamycin
      decreased the gene expression of the mitochondrial transcriptional regulators PGC
      1alpha, oestrogen-related receptor alpha and nuclear respiratory factors,
      resulting in a decrease in mitochondrial gene expression and oxygen consumption.
      Using computational genomics, we identified the transcription factor yin-yang 1
      (YY1) as a common target of mTOR and PGC-1alpha. Knockdown of YY1 caused a
      significant decrease in mitochondrial gene expression and in respiration, and YY1
      was required for rapamycin-dependent repression of those genes. Moreover, mTOR
      and raptor interacted with YY1, and inhibition of mTOR resulted in a failure of
      YY1 to interact with and be coactivated by PGC-1alpha. We have therefore
      identified a mechanism by which a nutrient sensor (mTOR) balances energy
      metabolism by means of the transcriptional control of mitochondrial oxidative
      function. These results have important implications for our understanding of how
      these pathways might be altered in metabolic diseases and cancer.

PMID- 18046415
TI  - Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain
      interface.
AB  - Members of the epidermal growth factor receptor family (EGFR/ERBB1, ERBB2/HER2,
      ERBB3/HER3 and ERBB4/HER4) are key targets for inhibition in cancer therapy.
      Critical for activation is the formation of an asymmetric dimer by the
      intracellular kinase domains, in which the carboxy-terminal lobe (C lobe) of one
      kinase domain induces an active conformation in the other. The cytoplasmic
      protein MIG6 (mitogen-induced gene 6; also known as ERRFI1) interacts with and
      inhibits the kinase domains of EGFR and ERBB2 (refs 3-5). Crystal structures of
      complexes between the EGFR kinase domain and a fragment of MIG6 show that a
      approximately 25-residue epitope (segment 1) from MIG6 binds to the distal
      surface of the C lobe of the kinase domain. Biochemical and cell-based analyses
      confirm that this interaction contributes to EGFR inhibition by blocking the
      formation of the activating dimer interface. A longer MIG6 peptide that is
      extended C terminal to segment 1 has increased potency as an inhibitor of the
      activated EGFR kinase domain, while retaining a critical dependence on segment 1.
      We show that signalling by EGFR molecules that contain constitutively active
      kinase domains still requires formation of the asymmetric dimer, underscoring the
      importance of dimer interface blockage in MIG6-mediated inhibition.

PMID- 18046419
TI  - Inhibition of TGF-beta expression: a novel role for thiazolidinediones to
      implement renoprotection in diabetes.
AB  - Actual strategies to delay progression of diabetic nephropathy provide imperfect
      protection when started late in the course of the disease. Ohtomo et al. now
      demonstrate that thiazolidinedione treatment was associated with a remarkable
      improvement in proteinuria and renal function, offering a new potential treatment
      for diabetic nephropathy.

PMID- 18046416
TI  - The centromere geometry essential for keeping mitosis error free is controlled by
      spindle forces.
AB  - Accurate segregation of chromosomes, essential for the stability of the genome,
      depends on 'bi-orientation'-simultaneous attachment of each individual chromosome
      to both poles of the mitotic spindle. On bi-oriented chromosomes, kinetochores
      (macromolecular complexes that attach the chromosome to the spindle) reside on
      the opposite sides of the chromosome's centromere. In contrast, sister
      kinetochores shift towards one side of the centromere on 'syntelic' chromosomes
      that erroneously attach to one spindle pole with both sister kinetochores.
      Syntelic attachments often arise during spindle assembly and must be corrected to
      prevent chromosome loss. It is assumed that restoration of proper centromere
      architecture occurs automatically owing to elastic properties of the centromere.
      Here we test this assumption by combining laser microsurgery and chemical biology
      assays in cultured mammalian cells. We find that kinetochores of syntelic
      chromosomes remain juxtaposed on detachment from spindle microtubules. These
      findings reveal that correction of syntelic attachments involves an extra step
      that has previously been overlooked: external forces must be applied to move
      sister kinetochores to the opposite sides of the centromere. Furthermore, we
      demonstrate that the shape of the centromere is important for spindle assembly,
      because bipolar spindles do not form in cells lacking centrosomes when multiple
      chromosomes with juxtaposed kinetochores are present. Thus, proper architecture
      of the centromere makes an important contribution to achieving high fidelity of
      chromosome segregation.

PMID- 18046420
TI  - Genetic complexity in Joubert syndrome and related disorders.
AB  - The recent identification of RPGRIP1L as a Joubert syndrome gene brings the total
      of known genes to five. Three of these are also associated with the lethal Meckel
      syndrome, and two with Senior-Loken syndrome; both of these disorders share
      Joubert syndrome phenotypes, illustrating the genetic complexity of this.

PMID- 18046421
TI  - Thiazide diuretic monotherapy for hypertension: diuretic's dark side just got
      darker.
AB  - Diuretic monotherapy is the current recommendation of the Joint National
      Committee on Prevention, Detection, Evaluation, and Treatment of High Blood
      Pressure for initial antihypertensive therapy. There is mounting concern,
      however, that the benefits of diuretic's superior blood pressure control may be
      offset by its multiple metabolic disturbances that increase cardiovascular risk.
      Reungjui et al. document a new concern, nephrotoxicity by thiazide monotherapy.
      This and other recently published evidence of diuretic's 'dark side' is
      discussed.

PMID- 18046423
TI  - The Case | an elderly diabetic man with urinary tract infection.

PMID- 18046424
TI  - Cobras in the bladder?

PMID- 18046425
TI  - Page kidney.

PMID- 18046426
TI  - Significant alterations of biodistribution and immune responses in Balb/c mice
      administered with adenovirus targeted to CD40(+) cells.
AB  - CD40 ligation has been shown to promote antigen-presenting functions of dendritic
      cells, which express CD40 receptor. Here we reported significantly altered
      biodistribution and immune responses with the use of CD40-targeted adenovirus.
      Compared with unmodified adenovirus 5, the CD40-targeted adenovirus following
      intravenous administration (i.v.) resulted in increased transgene expressions in
      the lung and thymus, which normally do not take up significant amounts of
      adenovirus. Intradermal injection saw modified adenovirus being mainly processed
      in local draining lymph nodes and skin. Following intranasal administration
      (i.n.), neither unmodified nor targeted viruses were found to be in the liver or
      spleen, which predominantly took up the virus following i.v. administration.
      However, inadvertent infection of the brain was found with unmodified
      adenoviruses, with the second highest gene expression among 14 tissues examined.
      Importantly, such undesirable effects were largely ablated with the use of
      targeted vector. Moreover, the targeted adenovirus elicited more sustained
      antigen-specific cellular immune responses (up to 17-fold) at later time points
      (30 days post boosting), but also significantly hampered humoral responses
      irrespective of administration routes. Additional data suggest the skewed immune
      responses induced by the targeted adenoviruses were not due to the identity of
      the transgene but more likely a combination of overall transgene load and CD40
      stimulation.

PMID- 18046427
TI  - How not to be seen: immune-evasion strategies in gene therapy.
AB  - The development of efficient and safe vectors for gene delivery paved the way for
      evolution of gene therapy as a new modality for treatment of various inherited
      disorders and for cancer. The current vectors, viral and non-viral, have their
      limitations. Innate and adaptive immune responses to vector particles and
      components may restrict the efficiency of gene transfer and the persistence of
      expression of the transgene. Results from preclinical studies in animals and more
      recently data from clinical studies have demonstrated the potential impact of the
      cellular and the humoral immune response on the therapeutic efficacy. Not only
      the vector components, but also the transgene products may induce an immune
      response that negatively affects the therapeutic efficacy. The induction of a
      cytotoxic T-cell response to transgene-encoded peptides, as well as the
      production of antibodies directed against secreted proteins have been reported in
      preclinical and clinical studies, and these may thwart those applications that
      require long-term expression. Here we will review some of the options to blunt
      the acquired immune responses to transgene-encoded polypeptides.

PMID- 18046428
TI  - Analysis of factor VIII mediated suppression of lentiviral vector titres.
AB  - Effective gene therapy for haemophilia A necessitates a vector system that is not
      subject to a pre-existing immune response, has adequate coding capacity, gives
      long-term expression and preferably can target non-dividing cells. Vector systems
      based on lentiviruses such as equine infectious anaemia virus (EIAV) fulfil these
      criteria for the delivery of factor VIII (FVIII). We have found that B domain
      deleted (BDD) FVIII protein inhibits functional viral particle production when co
      expressed with the EIAV vector system. Although particle numbers (as measured by
      reverse transcriptase activity) are near normal, RNA genome levels are reduced
      and measurement of integrated copies revealed the virus is severely defective in
      its ability to transduce target cells. This is due to the absence of sufficient
      vesicular stomatitis virus glycoprotein (VSV-G) envelope on viral particles
      derived from cells expressing FVIII. By using an internal tissue-specific
      promoter, that has low activity in the producer cells, to drive expression of
      FVIII we have overcome this inhibitory effect allowing us to generate titres
      approaching those obtained with vector genomes encoding reporter genes.
      Furthermore, we report that codon optimization of the full-length FVIII gene
      increased vector titres approximately 10-fold in addition to substantially
      improving expression per integrated vector copy.

PMID- 18046429
TI  - Toward 'SMART' stem cells.
AB  - Stem cell research is at the heart of regenerative medicine, which holds great
      promise for the treatment of many devastating disorders. However, in addition to
      hurdles posed by well-publicized ethical issues, this emerging field presents
      many biological challenges. What is a stem cell? How are embryonic stem cells
      different from adult stem cells? What are the physiological bases for
      therapeutically acceptable stem cells? In this editorial review, I will briefly
      discuss these superficially simple but actually rather complex issues that
      surround this fascinating cell type. The goal of this special issue on stem cells
      in Gene Therapy is to review some fundamental and critical aspects of current
      stem cell research that have translational potential.

PMID- 18046430
TI  - Two-hour glucose predicts the development of hypertension over 5 years: the
      AusDiab study.
AB  - Elevated 2-h plasma glucose concentration (2hPG) from an oral glucose tolerance
      (OGTT) test more strongly predicts risk of subsequent cardiovascular disease than
      fasting plasma glucose (FPG), but the association between these glucose
      measurements and hypertension risk is less clear. We examined the association
      between 2hPG, FPG and risk of hypertension. We conducted a prospective
      observational study (The Australian Diabetes, Obesity and Lifestyle Study
      AusDiab) among 4413 Australian residents who attended a baseline (1999-2000) and
      follow-up (2004-2005) examinations. Measurements included blood pressure (mean of
      two readings), 75 g OGTT, fasting insulin, anthropometrics, dietary and alcohol
      intake, medical history and physical activity. Hypertension was defined as a
      systolic blood pressure (SBP)> or =140 or a diastolic blood pressure (DBP)> or
      =90 mm Hg or treatment with medication for hypertension. HOMA-S was calculated as
      a measure of insulin sensitivity using the HOMA2 calculator. Hypertension
      developed in 14% of the 4306 subjects available for this analysis. Higher 2hPG
      was significantly related to greater risk of hypertension after adjustment for
      age, gender, FPG, BMI (baseline and difference), waist circumference (baseline
      and difference), education, exercise, alcohol intake, baseline SBP and smoking
      (OR (95% CI) 1.12 (1.01 to 1.23)), but no significant association was seen
      between FPG and hypertension in this model (1.02 (0.88-1.19)). Further adjustment
      for HOMA-S did not change these findings. Higher baseline 2hPG was more strongly
      associated with an increase in SBP than in DBP over 5 years. We conclude that
      higher 2hPG predicted future hypertension occurrence in this population.

PMID- 18046431
TI  - Telomere length may be associated with hypertension.

PMID- 18046433
TI  - Variation in recorded blood pressure terminal digit bias in general practice.
AB  - This study aims to identify the extent of terminal digit bias in routinely
      recorded blood pressures (BP) across a number of different general practices and
      report on changes in terminal digit bias over a 10-year period. It also explores
      the effect this may have had on the mean recorded BP in this population. BP
      records were taken from The Health Improvement Network database containing
      anonymized patient records from information entered by UK general practices in
      the financial years 1996-1997 to 2005-2006. The proportion of measurements ending
      in zero and the mean BP readings were calculated for each practice and for each
      year of data.Over this 10-year period the percentage of systolic BPs with zero
      terminal digits fell from 71.2 to 36.7% and mean recorded BP fell from 152.3 to
      145.3 mm Hg. Correcting the BPs to remove terminal digit bias indicates a 2-3 mm
      Hg underestimation of the mean population systolic BP over this period. The
      between-practice variation in the percentage of zero terminal digit readings
      increased from 3.5 to 6.5 s.d. Although it is welcome to see a reduction in
      terminal digit bias, it is worrying to see the increase in variation between
      practices. There is evidence that terminal digit bias may lead to potential
      misclassification and inappropriate treatment of hypertensive patients. The
      increase in variation observed may therefore lead to an increased variation in
      the quality of care given to patients.

PMID- 18046434
TI  - Effect of angiotensin-converting enzyme inhibitors on systemic inflammation and
      myocardial sympathetic innervation in normotensive patients with type 2 diabetes
      mellitus.
AB  - Diabetes mellitus (DM) may cause an increase in the inflammatory status and
      oxidative stress as well as sympathetic nervous system overactivity, even in the
      absence of any other organic heart disease. We investigated the effect of
      perindopril, an angiotensin-converting enzyme inhibitor (ACE-i), on indexes of
      systemic inflammation and oxidative stress in normotensive patients with type 2
      DM. We also examined the effect of the drug on the disturbances of left
      ventricular myocardial adrenergic innervation that may be seen in these patients.
      We studied 62 normotensive patients with type 2 DM, who were randomized to
      receive perindopril (n=32) or placebo (n=30). At the start of the study and after
      6 months' therapy blood samples were taken to evaluate total peroxides (TP),
      interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), and the
      patients underwent a (123)I-metaiodobenzylguanidine myocardial scintigraphy
      study. ACE-i caused a significant reduction in levels of cytokines and TP
      (P<0.001 for IL-6 and TNF-alpha, P=0.001 for TP). There was also a reduction in
      total defect score (P<0.001) and the heart to mediastinum ratio at 10 min and 4 h
      was improved (P<0.001 for both). No significant alterations were observed in the
      placebo group. Our data indicate that the addition of ACE-i to the medication of
      normotensive diabetic type 2 patients may improve the disturbed myocardial
      adrenergic innervation, the systemic inflammatory status and oxidative stress.
      Our findings indicate the cardioprotective action of ACE-i and suggest that
      earlier treatment might be appropriate in those patients.

PMID- 18046435
TI  - Linking inflammation and hypertension in humans: studies in Bartter's/Gitelman's
      syndrome patients.

PMID- 18046432
TI  - Randomized study of traditional versus aggressive systolic blood pressure control
      (Cardio-Sis): rationale, design and characteristics of the study population.
AB  - The hypothesis that a therapeutic strategy aimed at lowering systolic blood
      pressure (SBP) below 130 mm Hg is superior to a conventional strategy targeted at
      below 140 mm Hg in hypertensive subjects has never been tested in randomized
      intervention studies. The Studio Italiano Sugli Effetti Cardiovascolari del
      Controllo della Pressione Arteriosa Sistolica (Cardio-Sis) is a multi-centre
      study in non-diabetic, treated hypertensive subjects aged >55 years with
      uncontrolled SBP (>or=150 mm Hg) and at least one additional cardiovascular risk
      factor (ClinicalTrials.gov identifier: NCT00421863). Subjects are randomized to
      an SBP goal <140 mm Hg (conventional) or <130 mm Hg (aggressive), independently
      of baseline and achieved diastolic blood pressure (BP). Anti-hypertensive drugs
      dispensed for the study are restricted to a list of specific drugs. The primary
      outcome of the study is based on regression of left ventricular hypertrophy (LVH)
      using electrocardiography (ECG). The hypothesis is that subjects without LVH
      regression or with new development of LVH 2 years after randomization are 19%
      with conventional strategy and 12% with aggressive strategy. Secondary outcome is
      a composite pool of pre-specified fatal and non-fatal events. Randomization of
      1111 subjects was completed by February 2007. Mean age of subjects (41% men) at
      entry was 67 years. BP was 158/87 mm Hg (systolic/diastolic) and prevalence of
      LVH by ECG was 21.0%. Cardio-Sis is the first randomized study specifically
      designed to compare two different SBP goals. Results will be broadly applicable
      to subjects with uncontrolled SBP under anti-hypertensive treatment.

PMID- 18046436
TI  - Hiding in the shadows of the HIV epidemic: obesity and hypertension in a rural
      population with very high HIV prevalence in South Africa.

PMID- 18046437
TI  - Blood pressure levels correlate with intra-individual variability using an
      automated device in early pregnancy.
AB  - This study reports on the interdependence of intra-individual blood pressure (BP)
      variability and the BP level in early pregnancy. The higher the BP, the more
      exaggerated the drop from the first to the second reading and the higher the
      intra-individual standard deviation.

PMID- 18046439
TI  - Drug Insight: impulse control disorders and dopamine therapies in Parkinson's
      disease.
AB  - Impulse control disorders (ICDs) constitute a group of relatively common
      psychiatric conditions. ICDs typically involve pleasurable or hedonic behaviors
      (e.g. gambling, shopping or sex) that are performed repetitively, excessively or
      compulsively, to an extent that interferes in major areas of life functioning.
      Over the past decade, case reports, case studies and controlled examinations have
      reported ICDs in neurological patients, particularly those with Parkinson's
      disease (PD). A relationship between dopamine agonist treatment and ICDs was
      initially suggested on the basis of clinical observations, and subsequent
      systematic studies have provided more-substantial support for this association.
      Ongoing studies of the clinical characteristics of individuals with PD with and
      without ICDs suggest that certain individuals might be at increased risk of
      developing ICDs during PD treatment. Emerging data suggest that the association
      between dopamine agonists and ICDs extends into other neurological patient
      populations in which these agents are employed, such as those with restless legs
      syndrome. In this article, we summarize current knowledge regarding ICDs, review
      their relationships with PD and its treatments, provide practical clinical
      recommendations based on existing data, and suggest avenues for future research
      directed at advancing clinical care strategies.

PMID- 18046440
TI  - Surgery Insight: surgical management of epilepsy.
AB  - Epilepsy surgery has been shown to be an effective treatment for patients with
      intractable epilepsy. The only randomized controlled trial conducted in this
      setting to date found a dramatic advantage for surgery over medical treatment in
      temporal lobe epilepsy. In carefully selected patients, epilepsy surgery can
      control seizures, improve quality of life and reduce costs of medical care.
      Advances in diagnostic techniques are likely to improve patient selection,
      facilitate localization of epileptic foci and functional areas, and enable better
      prediction of outcomes.

PMID- 18046441
TI  - Mechanisms of disease: the PI3K-Akt-PTEN signaling node--an intercept point for
      the control of angiogenesis in brain tumors.
AB  - The overall prognosis for patients with high-grade glioma remains dismal, despite
      advances in treatment modalities including neurosurgery, radiation therapy and
      conventional cytotoxic chemotherapy. In this article, we review literature that
      provides a rationale for the use of antiangiogenic therapy to improve the
      treatment of high-grade neoplasms in the CNS. In particular, we focus our
      discussion on the central role of the phosphatidylinositol 3-kinase-Akt-
      phosphatase and tensin homolog (PI3K-Akt-PTEN) axis as a potential molecular
      target for the control of angiogenesis in brain tumors via the coordinated
      control of cell division, tumor growth, angiogenesis, apoptosis, invasion and
      cellular metabolism in the tumor and stromal compartments. We suggest that
      instead of inhibiting a single cell surface receptor, thereby leaving other
      receptors free to pulse survival, proliferative, angiogenic and invasive signals,
      a more effective way to approach the design of targeted therapy against brain
      tumors is to inhibit a nodal point where redundant cell surface receptor signals
      converge to transmit important, relatively conserved signaling events within the
      cell. The epigenetic and post-translational regulation of PI3K-Akt-PTEN signaling
      has a prominent role in brain tumor pathogenesis, and we therefore suggest that
      PI3K could be an important target for therapies that target brain tumors.

PMID- 18046442
TI  - Familial adenomatous polyposis in a patient with unexplained mental retardation.
AB  - BACKGROUND: A 22-year-old woman was referred to a genomic medicine clinic for
      evaluation of suspected Prader-Willi syndrome (PWS) after normal DNA methylation
      studies on chromosome 15 were obtained. Features suggestive of PWS included
      mental retardation, short stature, obesity, hypotonia, and small hands and feet.
      The patient, however, lacked many PWS-defining behavioral features, including
      hyperphagia, compulsive skin picking, and food-seeking behaviors. INVESTIGATIONS:
      DNA methylation studies on chromosome 15 were completed before the patient's
      presentation. At the genomic medicine clinic, she underwent standard karyotyping,
      array comparative genomic hybridization, fluorescent in situ hybridization
      analysis, colonoscopy, endoscopy, thyroid ultrasound, and thyroid fine needle
      aspiration biopsy. DIAGNOSIS: Familial adenomatous polyposis with mental
      retardation, caused by an interstitial deletion of the long arm of chromosome 5
      encompassing the APC (adenomatous polyposis coli) tumor suppressor locus.
      MANAGEMENT: Colectomy with ileorectal anastomosis and thyroidectomy with
      subsequent iodine-131 therapy. The patient also underwent genetic counseling and
      was prescribed a program of caloric reduction and exercise.

PMID- 18046443
TI  - T-cell lymphomas in T-cell-specific Pten-deficient mice originate in the thymus.
AB  - Phosphatase and tensin homolog deleted on chromosome 10 (Pten) is a tumor
      suppressor protein whose loss of lipid phosphatase activity is associated with
      lymphomagenesis. We made use of the Cre-loxP system to delete Pten expression in
      Lck- or CD4-expressing T-lineage cells. Mice initially showed modest thymic
      hyperplasia and subsequently developed expanding and infiltrating T-cell
      lymphomas, leading to a premature death within 5 to 23 weeks. Frequently, all
      thymocyte and peripheral T-cell populations displayed phenotypes characteristic
      for immature developing thymocyte precursors and shared elevated levels of
      clonally rearranged T-cell receptor (TCR) beta chains. In concert, CD2, CD5,
      CD3epsilon and CD44, proteins associated with increased expression and signaling
      capacity of both the immature pre-TCR and the mature alphabetaTCR, were more
      abundantly expressed, reflecting a constitutive state of activation. Although
      most T-cell lymphomas had acquired the capability to infiltrate the periphery,
      not all populations left the thymus and expanded clonally exclusively in the
      thymus. In line with this, only transplantation of thymocytes with infiltrating
      capacity gave rise to T-cell lymphoma in immunodeficient recipients. These
      results indicate that T-cell-specific Pten deletion during various stages of
      thymocyte development gives rise to clonally expanding T-cell lymphomas that
      frequently infiltrate the periphery, but originate in the thymus.

PMID- 18046444
TI  - Low MCL-1 mRNA expression correlates with prolonged survival in B-cell chronic
      lymphocytic leukemia.

PMID- 18046445
TI  - Fresh frozen plasma contains free asparagine and may replace the plasma
      asparagine pool during L-asparaginase therapy.

PMID- 18046447
TI  - The BCL-2 promoter (-938C>A) polymorphism does not predict clinical outcome in
      chronic lymphocytic leukemia.
AB  - The (-938C>A) polymorphism in the promoter region of the BCL-2 gene was recently
      associated with inferior time to treatment and overall survival in B-cell chronic
      lymphocytic leukemia (CLL) patients displaying the -938A/A genotype and may thus
      serve as an unfavorable genetic marker in CLL. Furthermore, the -938A/A genotype
      was associated with increased expression of Bcl-2. To investigate this further,
      we analyzed the -938 genotypes of the BCL-2 gene in 268 CLL patients and
      correlated data with treatment status, overall survival and known prognostic
      factors, for example, Binet stage, immunoglobulin heavy-chain variable (IGHV)
      mutational status and CD38 expression. In contrast to the recent report, the
      current cohort of CLL patients showed no differences either in time to treatment
      or overall survival in relation to usage of a particular genotype. In addition,
      no correlation was evident between the (-938C>A) genotypes and IGHV mutational
      status, Binet stage or CD38. Furthermore, the polymorphism did not appear to
      affect the Bcl-2 expression at the RNA level. Taken together, our data do not
      support the use of the (-938C>A) BCL-2 polymorphism as a prognostic marker in CLL
      and argue against its postulated role in modulating Bcl-2 levels.

PMID- 18046446
TI  - Atacicept (TACI-Ig) inhibits growth of TACI(high) primary myeloma cells in SCID
      hu mice and in coculture with osteoclasts.
AB  - APRIL (a proliferation-inducing Ligand) and BLyS/BAFF (B-lymphocyte stimulator/B
      cell-activating factor of the TNF (tumor necrosis factor) family have been shown
      to be the survival factors for certain myeloma cells in vitro. BAFF binds to the
      TNF-related receptors such as B-cell maturation antigen (BCMA), transmembrane
      activator and CAML interactor (TACI) and BAFFR, whereas APRIL binds to TACI and
      BCMA and to heparan sulfate proteoglycans (HSPG) such as syndecan-1. TACI gene
      expression in myeloma reportedly can distinguish tumors with a signature of
      microenvironment dependence (TACI(high)) versus a plasmablastic signature
      (TACI(low)). We tested the effect of atacicept (formerly TACI-Ig, which blocks
      APRIL and BAFF) and BAFFR-Ig (which blocks BAFF only) on primary myeloma growth
      in the SCID-hu model and in coculture with osteoclasts. With only few exceptions,
      atacicept and to a lesser extent BAFFR-Ig, inhibited growth of TACI(high) but not
      TACI(low) myeloma samples in vivo and ex vivo, and the response rate was
      inversely correlated with TACI expression. Most TACI(high) myeloma cells were
      molecularly classified as being low risk with our recently described 70-gene
      model. APRIL and BAFF were highly expressed by osteoclasts and were upregulated
      in myeloma cells after coculture with osteoclasts. Our findings suggest that
      APRIL plays an essential role in the survival of TACI(high) bone marrow-dependent
      myeloma cells and TACI gene expression may be a useful predictive marker for
      patients who could benefit from atacicept treatment.

PMID- 18046448
TI  - NK cell receptors and their ligands in leukemia.
AB  - Human natural killer (NK) cells are built to kill abnormal cells but to preserve
      autologous normal cells. To accomplish this task, they are equipped with a large
      number of inhibiting and activating receptors. Ligation with corresponding
      ligands will determine whether the NK cell becomes activated to destroy the
      abnormal cell. This review will focus on the abnormalities of NK cell receptors
      and their putative ligands found in patients with leukemia, which can lead to an
      inadequate function of NK cells allowing these malignant cells to escape from NK
      cell destruction. In recent years it has become clear that NK cells in the
      haploidentical hematopoietic stem cell transplantation (HSCT) setting are very
      effective in eliminating residual acute myeloid, but not acute lymphoid, leukemic
      cells. In this regard, we also reviewed published studies of retrospective
      cohorts of HSCT investigating the potential beneficial effect of killer-cell
      immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) ligands on
      NK alloreactivity. Manipulating NK cell inhibition or activation could lead to
      new forms of immunotherapy, ultimately leading to the elimination of resistant
      leukemic cells.

PMID- 18046449
TI  - The BCL2 rheostat in glucocorticoid-induced apoptosis of acute lymphoblastic
      leukemia.
AB  - Glucocorticoid (GC)-induced apoptosis is essential in the treatment of acute
      lymphoblastic leukemia (ALL) and related malignancies. Pro- and anti-apoptotic
      members of the BCL2 family control many forms of apoptotic cell death, but the
      extent to which this survival 'rheostat' is involved in the beneficial effects of
      GC therapy is not understood. We performed systematic analyses of expression, GC
      regulation and function of BCL2 molecules in primary ALL lymphoblasts and a
      corresponding in vitro model. Affymetrix-based expression profiling revealed that
      the response included regulations of pro-apoptotic and, surprisingly, anti
      apoptotic BCL2 family members, and varied among patients, but was dominated by
      induction of the BH3-only molecules BMF and BCL2L11/Bim and repression of
      PMAIP1/Noxa. Conditional lentiviral gene overexpression and knock-down by RNA
      interference in the CCRF-CEM model revealed that induction of Bim, and to a
      lesser extent that of BMF, was required and sufficient for apoptosis. Although
      anti-apoptotic BCL2 members were not regulated consistently by GC in the various
      systems, their overexpression delayed, whereas their knock-down accelerated, GC
      induced cell death. Thus, the combined clinical and experimental data suggest
      that GCs induce both pro- and anti-apoptotic BCL2 family member-dependent
      pathways, with the outcome depending on cellular context and additional signals
      feeding into the BCL2 rheostat.

PMID- 18046450
TI  - Enhanced antitumor activity by a selective conditionally replicating adenovirus
      combining with MDA-7/interleukin-24 for B-lymphoblastic leukemia via induction of
      apoptosis.
AB  - Conditionally replicating adenoviruses (CRAds) represent a promising new platform
      for anticancer therapy. However, CRAds have been evaluated little in
      hematopoietic malignancies because of the lack of expression of coxsackie
      adenovirus receptor (CAR) on their cell surface. In this study, we showed that
      CAR was expressed on two types of lymphoblastic leukemia cell lines and primary
      leukemia cells, and that ZD55, a CRAd, exerted a potent antileukemia effect in
      vitro and in vivo. Furthermore, ZD55 expressing melanoma differentiation
      associated gene-7/interleukin-24 (ZD55-IL-24) elicited significant enhanced
      antileukemia activity comparing with ZD55, concomitant with upregulation of RNA
      dependent protein kinase R (PKR), increased phosphorylation of p38 mitogen
      activated protein kinase (MAPK), and induction of endoplasmic reticulum (ER)
      stress. These data for the first time indicate that MDA-7/IL-24 exerts its
      antitumor effect on leukemia cells via multiple pathways, and suggest that
      oncolytic adenoviruses, ZD55 and ZD55-IL-24 could potentially be used against CAR
      expressing hematological malignancies such as B-lymphoblastic leukemia/lymphoma
      and some myeloid leukemia.

PMID- 18046451
TI  - Do beta2 microglobulin levels affect survival of newly diagnosed myeloma patients
      with translocation t(4;14) or 17p13 deletion treated with conventional
      chemotherapy?

PMID- 18046452
TI  - A versatile interaction platform on the Mex67-Mtr2 receptor creates an overlap
      between mRNA and ribosome export.
AB  - The transport receptor Mex67-Mtr2 functions in mRNA export, and also by a loop
      confined surface on the heterodimer binds to and exports pre-60S particles. We
      show that Mex67-Mtr2 through the same surface that recruits pre-60S particles
      interacts with the Nup84 complex, a structural module of the nuclear pore complex
      devoid of Phe-Gly domains. In vitro, pre-60S particles and the Nup84 complex
      compete for an overlapping binding site on the loop-extended Mex67-Mtr2 surface.
      Chemical crosslinking identified Nup85 as the subunit in the Nup84 complex that
      directly binds to the Mex67 loop. Genetic studies revealed that this interaction
      is crucial for mRNA export. Notably, pre-60S subunit export impaired by mutating
      Mtr2 or the 60S adaptor Nmd3 could be partially restored by second-site mutation
      in Nup85 that caused dissociation of Mex67-Mtr2 from the Nup84 complex. Thus, the
      Mex67-Mtr2 export receptor employs a versatile binding platform on its surface
      that could create a crosstalk between mRNA and ribosome export pathways.

PMID- 18046453
TI  - MHC class II molecules on the move for successful antigen presentation.
AB  - Major histocompatibility complex class II (MHC II) molecules are targeted to
      endocytic compartments, known as MIIC, by the invariant chain (Ii) that is
      degraded upon arrival in these compartments. MHC II acquire antigenic fragments
      from endocytosed proteins for presentation at the cell surface. In a unique and
      complex series of reactions, MHC II succeed in exchanging a remaining fragment of
      Ii for other protein fragments in subdomains of MIIC before transport to the cell
      surface. Here, the mechanisms regulating loading and intracellular trafficking of
      MHC II are discussed.

PMID- 18046454
TI  - Spatial recruitment and activation of the Fes kinase by ezrin promotes HGF
      induced cell scattering.
AB  - The remodeling of epithelial monolayers induced by hepatocyte growth factor (HGF)
      results in the reorganization of actin cytoskeleton and cellular junctions. We
      previously showed that the membrane-cytoskeleton linker ezrin plays a major role
      in HGF-induced morphogenic effects. Here we identified a novel partner of
      phosphorylated ezrin, the Fes kinase, that acts downstream of ezrin in HGF
      mediated cell scattering. We found that Fes interacts directly, through its SH2
      domain, with ezrin phosphorylated at tyrosine 477. We show that in epithelial
      cells, activated Fes localizes either to focal adhesions or cell-cell contacts
      depending on cell confluency. The recruitment and the activation of Fes to the
      cell-cell contacts in confluent cells depend on its interaction with ezrin. When
      this interaction is impaired, Fes remains in focal adhesions and as a consequence
      the cells show defective spreading and scattering in response to HGF stimulation.
      Altogether, these results provide a novel mechanism whereby ezrin/Fes interaction
      at cell-cell contacts plays an essential role in HGF-induced cell scattering and
      implicates Fes in the cross-talk between cell-cell and cell-matrix adhesion.

PMID- 18046455
TI  - Crystal structure of human XLF/Cernunnos reveals unexpected differences from
      XRCC4 with implications for NHEJ.
AB  - The recently characterised 299-residue human XLF/Cernunnos protein plays a
      crucial role in DNA repair by non-homologous end joining (NHEJ) and interacts
      with the XRCC4-DNA Ligase IV complex. Here, we report the crystal structure of
      the XLF (1-233) homodimer at 2.3 A resolution, confirming the predicted
      structural similarity to XRCC4. The XLF coiled-coil, however, is shorter than
      that of XRCC4 and undergoes an unexpected reverse in direction giving rise to a
      short distorted four helical bundle and a C-terminal helical structure wedged
      between the coiled-coil and head domain. The existence of a dimer as the major
      species is confirmed by size-exclusion chromatography, analytical
      ultracentrifugation, small-angle X-ray scattering and other biophysical methods.
      We show that the XLF structure is not easily compatible with a proposed XRCC4:XLF
      heterodimer. However, we demonstrate interactions between dimers of XLF and XRCC4
      by surface plasmon resonance and analyse these in terms of surface properties,
      amino-acid conservation and mutations in immunodeficient patients. Our data are
      most consistent with head-to-head interactions in a 2:2:1 XRCC4:XLF:Ligase IV
      complex.

PMID- 18046456
TI  - Hsp90-mediated cytosolic refolding of exogenous proteins internalized by
      dendritic cells.
AB  - Dendritic cells efficiently internalize exogenous protein antigens by fluid-phase
      uptake and receptor-mediated endocytosis. Such antigens contribute to cross
      presentation by being translocated into the cytosol for proteasomal degradation,
      which liberates immunogenic peptides that can bind to major histocompatibility
      complex (MHC) class I molecules after being transported into the endoplasmic
      reticulum (ER). MHC class I-peptide complexes are then expressed on the cell
      surface and presented to CD8+ T cells. Here we show that internalized proteins
      can have an alternative fate. After internalization, proteins are first unfolded
      to allow translocation into the cytosol using a pathway related to ER-associated
      degradation (ERAD). Subsequently the unfolded proteins can undergo cytosolic
      refolding assisted by the chaperone Hsp90. These observations not only clarify
      the cellular processes regulating cytosolic access following endocytosis, but
      also demonstrate that functional proteins can potentially regain their activity
      in the cytosol of dendritic cells.

PMID- 18046457
TI  - Structure-guided identification of a new catalytic motif of
      oligosaccharyltransferase.
AB  - Asn-glycosylation is widespread not only in eukaryotes but also in archaea and
      some eubacteria. Oligosaccharyltransferase (OST) catalyzes the co-translational
      transfer of an oligosaccharide from a lipid donor to an asparagine residue in
      nascent polypeptide chains. Here, we report that a thermophilic archaeon,
      Pyrococcus furiosus OST is composed of the STT3 protein alone, and catalyzes the
      transfer of a heptasaccharide, containing one hexouronate and two pentose
      residues, onto peptides in an Asn-X-Thr/Ser-motif-dependent manner. We also
      determined the 2.7-A resolution crystal structure of the C-terminal soluble
      domain of Pyrococcus STT3. The structure-based multiple sequence alignment
      revealed a new motif, DxxK, which is adjacent to the well-conserved WWDYG motif
      in the tertiary structure. The mutagenesis of the DK motif residues in yeast STT3
      revealed the essential role of the motif in the catalytic activity. The function
      of this motif may be related to the binding of the pyrophosphate group of lipid
      linked oligosaccharide donors through a transiently bound cation. Our structure
      provides the first structural insights into the formation of the oligosaccharide
      asparagine bond.

PMID- 18046458
TI  - Neural recognition molecules CHL1 and NB-3 regulate apical dendrite orientation
      in the neocortex via PTP alpha.
AB  - Apical dendrites of pyramidal neurons in the neocortex have a stereotypic
      orientation that is important for neuronal function. Neural recognition molecule
      Close Homolog of L1 (CHL1) has been shown to regulate oriented growth of apical
      dendrites in the mouse caudal cortex. Here we show that CHL1 directly associates
      with NB-3, a member of the F3/contactin family of neural recognition molecules,
      and enhances its cell surface expression. Similar to CHL1, NB-3 exhibits high
      caudal to low-rostral expression in the deep layer neurons of the neocortex. NB-3
      deficient mice show abnormal apical dendrite projections of deep layer pyramidal
      neurons in the visual cortex. Both CHL1 and NB-3 interact with protein tyrosine
      phosphatase alpha (PTPalpha) and regulate its activity. Moreover, deep layer
      pyramidal neurons of PTPalpha-deficient mice develop misoriented, even inverted,
      apical dendrites. We propose a signaling complex in which PTPalpha mediates CHL1
      and NB-3-regulated apical dendrite projection in the developing caudal cortex.

PMID- 18046459
TI  - Structure and functional analysis of the IGF-II/IGF2R interaction.
AB  - Embryonic development and normal growth require exquisite control of insulin-like
      growth factors (IGFs). In mammals the extracellular region of the cation
      independent mannose-6-phosphate receptor has gained an IGF-II-binding function
      and is termed type II IGF receptor (IGF2R). IGF2R sequesters IGF-II; imbalances
      occur in cancers and IGF2R is implicated in tumour suppression. We report crystal
      structures of IGF2R domains 11-12, 11-12-13-14 and domains 11-12-13/IGF-II
      complex. A distinctive juxtaposition of these domains provides the IGF-II-binding
      unit, with domain 11 directly interacting with IGF-II and domain 13 modulating
      binding site flexibility. Our complex shows that Phe19 and Leu53 of IGF-II lock
      into a hydrophobic pocket unique to domain 11 of mammalian IGF2Rs. Mutagenesis
      analyses confirm this IGF-II 'binding-hotspot', revealing that IGF-binding
      proteins and IGF2R have converged on the same high-affinity site.

PMID- 18046460
TI  - The post-rigor structure of myosin VI and implications for the recovery stroke.
AB  - Myosin VI has an unexpectedly large swing of its lever arm (powerstroke) that
      optimizes its unique reverse direction movement. The basis for this is an
      unprecedented rearrangement of the subdomain to which the lever arm is attached,
      referred to as the converter. It is unclear at what point(s) in the myosin VI
      ATPase cycle rearrangements in the converter occur, and how this would effect
      lever arm position. We solved the structure of myosin VI with an ATP analogue
      (ADP.BeF3) bound in its nucleotide-binding pocket. The structure reveals that no
      rearrangement in the converter occur upon ATP binding. Based on previously solved
      myosin structures, our structure suggests that no reversal of the powerstroke
      occurs during detachment of myosin VI from actin. The structure also reveals
      novel features of the myosin VI motor that may be important in maintaining the
      converter conformation during detachment from actin, and other features that may
      promote rapid rearrangements in the structure following actin detachment that
      enable hydrolysis of ATP.

PMID- 18046461
TI  - JNK phosphorylates synaptotagmin-4 and enhances Ca2+-evoked release.
AB  - Ca2+ influx induced by membrane depolarization triggers the exocytosis of
      secretory vesicles in various cell types such as endocrine cells and neurons.
      Peptidyl growth factors enhance Ca2+-evoked release, an effect that may underlie
      important adaptive responses such as the long-term potentiation of synaptic
      transmission induced by growth factors. Here, we show that activation of the c
      Jun N-terminal kinase (JNK) plays an essential role in nerve growth factor (NGF)
      enhancement of Ca2+-evoked release in PC12 neuroendocrine cells. Moreover, JNK
      associated with phosphorylated synaptotagmin-4 (Syt 4), a key mediator of NGF
      enhancement of Ca2+-evoked release in this system. NGF treatment led to
      phosphorylation of endogenous Syt 4 at Ser135 and translocation of Syt 4 from
      immature to mature secretory vesicles in a JNK-dependent manner. Furthermore,
      mutation of Ser135 abrogated enhancement of Ca2+-evoked release by Syt 4. These
      results provide a molecular basis for the effect of growth factors on Ca2+
      mediated secretion.

PMID- 18046462
TI  - Absence of the Thorpe-Ingold Effect by gem-Diphenyl Groups in Ring-Closing Enyne
      Metathesis.
AB  - In tandem ring-closing metathesis of alkynyl silaketals containing two different
      tethered olefins, the gem-dimethyl group showed the expected Thorpe-Ingold
      effect, thereby giving good level of group selectivity. Unexpectedly, however,
      the corresponding gem-diphenyl group did not show any Thorpe-Ingold effect for
      the ring closure reaction.

PMID- 18046463
TI  - Subjective comparison and evaluation of speech enhancement algorithms.
AB  - Making meaningful comparisons between the performance of the various speech
      enhancement algorithms proposed over the years, has been elusive due to lack of a
      common speech database, differences in the types of noise used and differences in
      the testing methodology. To facilitate such comparisons, we report on the
      development of a noisy speech corpus suitable for evaluation of speech
      enhancement algorithms. This corpus is subsequently used for the subjective
      evaluation of 13 speech enhancement methods encompassing four classes of
      algorithms: spectral subtractive, subspace, statistical-model based and Wiener
      type algorithms. The subjective evaluation was performed by Dynastat, Inc. using
      the ITU-T P.835 methodology designed to evaluate the speech quality along three
      dimensions: signal distortion, noise distortion and overall quality. This paper
      reports the results of the subjective tests.

PMID- 18046464
TI  - Spreading out of perturbations in reversible reaction networks.
AB  - Using an example of physical interactions between proteins, we study how a
      perturbation propagates in the equilibrium of a network of reversible reactions
      governed by the law of mass action. We introduce a matrix formalism to describe
      the linear response of all equilibrium concentrations to shifts in total
      abundances of individual reactants, and reveal its heuristic analogy to the flow
      of electric current in a network of resistors. Our main conclusion is that, on
      average, the induced changes in equilibrium concentrations decay exponentially as
      a function of network distance from the source of perturbation. We analyze how
      this decay is influenced by such factors as the topology of a network, binding
      strength, and correlations between concentrations of neighboring nodes. We find
      that the minimal branching of the network, small values of dissociation
      constants, and low equilibrium free (unbound) concentrations of reacting
      substances all decrease the decay constant and thus increase the range of
      propagation. Exact analytic expressions for the decay constant are obtained for
      the case of equally strong interactions and uniform as well as oscillating
      concentrations on the Bethe lattice. Our general findings are illustrated using a
      real network of protein-protein interactions in baker's yeast with experimentally
      determined protein concentrations.

PMID- 18046465
TI  - Social Affiliation and the Demand for Health Services: Caste and Child Health in
      South India.
AB  - This paper assesses the role of social affiliation, measured by caste, in shaping
      investments in child health. The special setting that we have chosen for the
      analysis - tea estates in the South Indian High Range - allows us to control
      nonparametrically for differences in income, access to health services, and
      patterns of morbidity across low caste and high caste households. In this
      controlled setting, low caste households spend more on their children's health
      than high caste households, reversing the pattern we would expect to find
      elsewhere in India. Moreover, health expenditures do not vary by gender within
      either caste group, in contrast once again with the male preference documented
      throughout the country. A simple explanation, based on differences in the returns
      to human capital across castes in the tea estates is proposed to explain these
      striking results.

PMID- 18046466
TI  - Voids, generic van der Waals equation of state, and transport coefficients of
      liquids.
AB  - In this Perspective, we discuss the role of voids in transport processes in
      liquids and the manner in which the concept of voids enters the generic van der
      Waals equation of state and the modified free volume theory. The density
      fluctuation theory is then discussed and we show how the density fluctuation
      theory can be made a molecular theory with the help of the modified free volume
      theory and the generic van der Waals equation of state. The confluence of the
      aforementioned three theories makes it possible to calculate the transport
      coefficients of liquids by using the information on the equilibrium pair
      correlation function, which can be calculated either by an integral equation
      theory or Monte Carlo simulations. A number of relations between transport
      coefficients are also presented, which are derived on the basis of the density
      fluctuation theory. Since they can be used to obtain one transport coefficient
      from another they can be very useful in handling experimental and theoretical
      data. An application of the modified free volume theory to polymer melts is
      discussed as an example for a theory of transport properties of complex liquids.

PMID- 18046467
TI  - Critical evaluation of mass spectrometric measurement of dissociation constants:
      accuracy and cross-validation against surface plasmon resonance and circular
      dichroism for the calmodulin-melittin system.
AB  - We present a comprehensive study for determining the binding affinity of a
      protein-ligand complex, using mass spectrometric methods. Mass spectrometry has
      been used to study noncovalent interactions for a number of years. However, the
      use of soft ionization mass spectrometry for quantitative analysis of
      noncovalently bound complexes is not widely accepted. This paper reports a
      comparison of MS methods against established methods such as surface plasmon
      resonance (SPR) and circular dichroism (CD) whose suitability for the
      quantitative assessment of noncovalent interactions is well known. ESI titration
      and MALDI-SUPREX were used as representative mass spectrometric methods for this
      work. We chose to study the calmodulin-melittin complex that presents three
      challenges: (i) it exhibits a high affinity (low nanomolar KD); (ii) complexes
      are formed only in the presence of a coactivator, calcium ions in this case; and
      (iii) the protein and the complex show a different ionization efficiency.
      Dissociation constants were obtained from each method for the selected system and
      compared thoroughly to elucidate pros and cons of the selected methodologies in
      terms of their ability for the determination of binding constants of protein
      ligand complexes. ESI titration, SPR, CD and MALDI-SUPREX yielded KD values in
      the low nanomolar range that are in general agreement with an older value
      reported in the literature. We also critically evaluated the limitations in
      particular of the MS methods and the associated data evaluation procedures. We
      present an improved evaluation of SUPREX data, as well as a detailed error
      analysis for all methods used.

PMID- 18046468
TI  - Microscopic Li self-diffusion parameters in the lithiated anode material Li4 +
      xTi5O12 (0 < or = x < or = 3) measured by 7Li solid state NMR.
AB  - The microscopic Li diffusion parameters in the lithiated spinel Li4 + xTi5O12,
      which is on its way to become a commercially used anode material in Li ion
      batteries, are probed for the first time via nuclear magnetic resonance
      spectroscopy.

PMID- 18046469
TI  - Application of a new theoretical procedure for calculating Kirkwood correlation
      factors in alkanol + hexane and alkanol + pentane mixtures.
AB  - A recently developed statistical mechanical model for calculating Kirkwood
      correlation factors gK in self associating liquids and liquid mixtures has been
      applied for the simultaneous description of gK, the molar enthalpy of mixing HEM
      and the infrared absorption of monomer alcoholic species as function of the
      composition in alkanol + hexane and alkanol + pentane mixtures (alkanol: butan-1
      ol, pentan-1-ol, hexan-1-ol, heptan-1-ol, sec-butanol, tert-butanol). The
      majority of parameters involved into the theory are obtained by independent
      quantum mechanical ab initio calculations of molecular clusters consisting of up
      to four alcohol molecules. As a consequence only two parameters have to be
      adjusted freely to each binary system, a third parameter responsible for the non
      specific intermolecular dispersion interaction has been adjusted within a limited
      range of possible values given by physical arguments. Excellent agreement between
      theory and experimental data of gK, HEM and IR absorbance is obtained covering
      the whole range of concentration including the temperature dependence of these
      properties without adjusting further parameters. The Kirkwood correlation factor
      gK turns out to be a sensitive response to peculiarities of the molecular
      structure of hydrogen bonded systems in the condensed liquid state. The
      successful application of the theoretical model opens a new way of a deeper and
      more reliable understanding of such liquid structures.

PMID- 18046470
TI  - Circular dichroism and absorption spectroscopy of merocyanine dimer aggregates:
      molecular properties and exciton transfer dynamics from time-dependent quantum
      calculations.
AB  - A wave packet approach to the calculation and interpretation of circular
      dichroism (CD) spectra is applied to the spectroscopy of aggregates of a
      merocyanine dye. A combined analysis of absorption and CD spectra allows for the
      extraction of geometric information and excited state electronic coupling. It is
      shown that in the case of dimer aggregates of a chiral merocyanine dye, it is
      possible to infer the dynamics of an exciton transfer directly from the CD
      spectrum. This relation is established via the Fourier relation to a time
      dependent correlation function reflecting the quantum dynamics in the dye
      aggregate.

PMID- 18046471
TI  - A high-field solid-state 35/37Cl NMR and quantum chemical investigation of the
      chlorine quadrupolar and chemical shift tensors in amino acid hydrochlorides.
AB  - A series of six L-amino acid hydrochloride salts has been studied by 35/37Cl
      solid-state NMR spectroscopy (at 11.75 and 21.1 T) and complementary quantum
      chemical calculations. Analyses of NMR spectra acquired under static and magic
      angle-spinning conditions for the six hydrochloride salts, those of aspartic
      acid, alanine, cysteine, histidine, methionine and threonine, allowed the
      extraction of information regarding the chlorine electric field gradient (EFG)
      and chemical shift tensors, including their relative orientation. Both tensors
      are found to be highly dependent on the local environment, with chlorine-35
      quadrupolar coupling constants (CQ) ranging from -7.1 to 4.41 MHz and chemical
      shift tensor spans ranging from 60 to 100 ppm; the value of CQ for aspartic acid
      hydrochloride is the largest in magnitude observed to date for an organic
      hydrochloride salt. Quantum chemical calculations performed on cluster models of
      the chloride ion environment demonstrated agreement between experiment and
      theory, reproducing CQ to within 18%. In addition, the accuracy of the calculated
      values of the NMR parameters as a function of the quality of the input structure
      was explored. Selected X-ray structures were determined (L-Asp HCl; L-Thr HCl) or
      re-determined (L-Cys HCl.H2O) to demonstrate the benefits of having accurate
      crystal structures for calculations. The self-consistent charge field
      perturbation model was also employed and was found to improve the accuracy of
      calculated quadrupolar coupling constants, demonstrating the impact of the
      neighbouring ions on the EFG tensor of the central chloride ion. Taken together,
      the present work contributes to an improved understanding of the factors
      influencing 35/37Cl NMR interaction tensors in organic hydrochlorides.

PMID- 18046472
TI  - High-resolution intermolecular zero-quantum coherence spectroscopy under
      inhomogeneous fields with effective solvent suppression.
AB  - Intermolecular zero-quantum coherences (iZQCs) are not susceptible to magnetic
      field inhomogeneities significantly larger than the dipolar correlation distance
      and can be used to obtain 1D high-resolution spectra in an inhomogeneous field.
      However, with the iZQC methods proposed previously, residual conventional single
      quantum coherences (SQCs) originating mainly from solvent resonance result in
      strong t(1) ridge noises. A modified HOMOGENIZED with an intermolecular double
      quantum filter (iDQF), named iDQF-HOMOGENIZED, is presented in this work to
      suppress the residual conventional SQC signals as well as solvent iZQC signals.
      The solvent-suppression efficiency of the iDQF-HOMOGENIZED is analyzed and a
      thorough comparison of the new sequence with several relevant pulse sequences is
      made. Dramatic resolution enhancement and solvent suppression in the measurements
      of a piece of grape sarcocarp suggest potential applications of the method in in
      vivo spectroscopy.

PMID- 18046473
TI  - The mechanism of H-bond rupture: the vibrational pre-dissociation of C2H2-HCl and
      C2H2-DCl.
AB  - Pair correlated fragment rovibrational distributions are presented following
      vibrational predissociation of the C2H2-DCl van der Waals dimer initiated by
      excitation of the asymmetric (asym) C-H stretch. The only observed fragmentation
      pathways are DCl (v= 0; j= 6-9)+ C2H2(nu2= 1; j= 1-5). These and previously
      reported data on the related C2H2-HCl species are analysed using the angular
      momentum (AM) method. Calculations accurately reproduce fragment rovibrational
      distributions following dissociation of the C2H2-HCl dimer initiated either by
      excitation of the asym C-H stretch or via the HCl stretch, and those from C2H2
      DCl initiated via asym C-H stretch excitation. The calculations demonstrate that
      the dimer is bent at the moment of dissociation. Several geometries are found
      that lead to H-bond breakage via a clearly identified set of fragment quantum
      states. The results suggest a hierarchy in the disposal of excess energy and
      angular momentum between fragment vibration, rotation and recoil. Deposition of
      the largest portion of energy into a C2H2 vibrational state sets an upper limit
      on HCl rotation, which then determines the energy and AM remaining for C2H2
      rotation and fragment recoil. Acceptor C2H2 vibrational modes follow a previously
      noted propensity, implying that the dissociating impulse must be able to induce
      appropriate nuclear motions both in the acceptor vibration and in rotation of the
      C2H2 fragment.

PMID- 18046474
TI  - Are electrostatic potentials between regions of different chemical composition
      measurable? The Gibbs-Guggenheim Principle reconsidered, extended and its
      consequences revisited.
AB  - As indicated by Gibbs and made explicit by Guggenheim, the electrical potential
      difference between two regions of different chemical composition cannot be
      measured. The Gibbs-Guggenheim Principle restricts the use of classical
      electrostatics in electrochemical theories as thermodynamically unsound with some
      few approximate exceptions, notably for dilute electrolyte solutions and
      concomitant low potentials where the linear limit for the exponential of the
      relevant Boltzmann distribution applies. The Principle invalidates the widespread
      use of forms of the Poisson-Boltzmann equation which do not include the non
      electrostatic components of the chemical potentials of the ions. From a
      thermodynamic analysis of the parallel plate electrical condenser, employing only
      measurable electrical quantities and taking into account the chemical potentials
      of the components of the dielectric and their adsorption at the surfaces of the
      condenser plates, an experimental procedure to provide exceptions to the
      Principle has been proposed. This procedure is now reconsidered and rejected. No
      other related experimental procedures circumvent the Principle. Widely-used
      theoretical descriptions of electrolyte solutions, charged surfaces and colloid
      dispersions which neglect the Principle are briefly discussed. MD methods avoid
      the limitations of the Poisson-Bolzmann equation. Theoretical models which
      include the non-electrostatic components of the inter-ion and ion-surface
      interactions in solutions and colloid systems assume the additivity of dispersion
      and electrostatic forces. An experimental procedure to test this assumption is
      identified from the thermodynamics of condensers at microscopic plate
      separations. The available experimental data from Kelvin probe studies are
      preliminary, but tend against additivity. A corollary to the Gibbs-Guggenheim
      Principle is enunciated, and the Principle is restated that for any charged
      species, neither the difference in electrostatic potential nor the sum of the
      differences in the non-electrostatic components of the thermodynamic potential
      difference between regions of different chemical compositions can be measured.

PMID- 18046475
TI  - Electronic properties of multifurcated bent hydrogen bonds CH3...Y and CH2...Y.
AB  - H-bonding angle angleYHX has an important effect on the electronic properties of
      the H-bond Y...HX, such as intra- and intermolecular hyperconjugations and
      rehybridization, and topological properties of electron density. We studied the
      multifurcated bent H-bonds of the proton donors H3CZ (Z = F, Cl, Br), H2CO and
      H2CF2 with the proton acceptors Cl(-) and Br(-) at the four high levels of
      theory: MP2/6-311++G(d,p), MP2/6-311++G(2df,2p), MP2/6-311++G(3df,3pd) and
      QCISD/6-311++G(d,p), and found that they are all blue-shifted. These complexes
      have large interaction energies, 7-12 kcal mol(-1), and large blue shifts, delta
      r(HC) = -0.0025 --0.006 A and delta v(HC) = 30-90 cm(-1). The natural bond
      orbital analysis shows that the blue shifts of these H-bonds Y...HnCZ are mainly
      caused by three factors: rehybridization; indirect intermolecular
      hyperconjugation n(Y) -->sigma*(CZ), in that the electron density from n(Y) of
      the proton acceptor is transferred not to sigma*(CH), but to sigma*(CZ) of the
      donor; intramolecular hyperconjugation n(Z) -->sigma*(CH), in that the electron
      density in sigma*(CH) comes back to n(Z) of the donor such that the occupancy in
      sigma*(CH) decreases. The topological properties of the electron density of the
      bifurcated H-bonds Y...H2CZ are similar to those of the usual linear H-bonds,
      there is a bond critical point between Y and each hydrogen, and a ring critical
      point inside the tetragon YHCH. However, the topological properties of electron
      density of the trifurcated H-bonds Y...H3CZ are essentially different from those
      of linear H-bonds, in that the intermolecular bond critical point, which
      represents a closed-shell interaction, is not between Y and hydrogen, but between
      Y and carbon.

PMID- 18046476
TI  - Hyperfine coupling dependence of the effects of weak magnetic fields on the
      recombination reactions of radicals generated from polymerisation
      photoinitiators.
AB  - The recombination reactions of free radicals formed from the photolysis of a
      series of polymerisation photoinitiators were studied using time-resolved
      infrared spectroscopy. All molecules showed Zeeman magnetic field effects (MFEs)
      in the field range 0-37 mT and those molecules that produced radical pairs with
      average hyperfine couplings greater than 5 mT showed substantial inverted field
      effects at fields of less than 10 mT (so-called low field effects, LFEs). Monte
      Carlo simulations with full treatment of all the isotropic hyperfine couplings in
      the spin Hamiltonian reproduced well the observed field effects. The use of the
      usual analysis based on the calculated B1/2 value for the radical pair was found
      to be inappropriate in systems with substantial LFEs, but simple correlations
      between this B1/2 value and the observed field features were established.

PMID- 18046478
TI  - Milestones in the development of photodynamic therapy and fluorescence diagnosis.
AB  - Many reviews on PDT have been published. This field is now so large, and embraces
      so many sub-specialties, from laser technology and optical penetration through
      diffusing media to a number of medical fields including dermatology,
      gastroenterology, ophthalmology, blood sterilization and treatment of microbial
      viral diseases, that it is impossible to cover all aspects in a single review.
      Here, we will concentrate on a few basic aspects, all important for the route of
      development leading PDT to its present state: early work on hematoporphyrin and
      hematoporphyrin derivative, second and third generation photosensitizers, 5
      aminolevulinic acid and its derivatives, oxygen and singlet oxygen, PDT effects
      on cell organelles, mutagenic potential, the basis for tumour selectivity, cell
      cooperativity, photochemical internalization, light penetration into tissue and
      the significance of oxygen depletion, photobleaching of photosensitizers, optimal
      light sources, effects on the immune system, and, finally, future trends.

PMID- 18046479
TI  - The role of oxygen monitoring during photodynamic therapy and its potential for
      treatment dosimetry.
AB  - Understanding of the biology of photodynamic therapy (PDT) has expanded
      tremendously over the past few years. However, in the clinical situation, it is
      still a challenge to match the extent of PDT effects to the extent of the disease
      process being treated. PDT requires drug, light and oxygen, any of which can be
      the limiting factor in determining efficacy at each point in a target organ. This
      article reviews techniques available for monitoring tissue oxygenation during
      PDT. Point measurements can be made using oxygen electrodes or luminescence-based
      optodes for direct measurements of tissue pO2, or using optical spectroscopy for
      measuring the oxygen saturation of haemoglobin. Imaging is considerably more
      complex, but may become feasible with techniques like BOLD MRI. Pre-clinical
      studies have shown dramatic changes in oxygenation during PDT, which vary with
      the photosensitizer used and the light delivery regimen. Better oxygenation
      throughout treatment is achieved if the light fluence rate is kept low as this
      reduces the rate of oxygen consumption. The relationship between tissue
      oxygenation and PDT effect is complex and remarkably few studies have directly
      correlated oxygenation changes during PDT with the final biological effect,
      although those that have confirm the value of maintaining good oxygenation. Real
      time monitoring to ensure adequate oxygenation at strategic points in target
      tissues during PDT is likely to be important, particularly in the image guided
      treatment of tumours of solid organs.

PMID- 18046480
TI  - Photophysical, electrochemical characteristics and cross-linking of STAT-3
      protein by an efficient bifunctional agent for fluorescence image-guided
      photodynamic therapy.
AB  - The photophysical, electrochemical and spectroscopic characteristics of a
      conjugate of 3-devinyl-3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) and a
      cyanine dye have been investigated both as a linked conjugate and as individual
      components. A photoexcitation of the HPPH moiety of the conjugate results in
      electron transfer from the singlet excited state of HPPH (1HPPH*) to the cyanine
      dye as well as that from the cyanine dye to 1HPPH* and is followed in both cases
      by facile back electron transfer to the ground state as indicated by time
      resolved fluorescence and transient absorption measurements. Intersystem crossing
      to the triplet excited state (3HPPH*) competes with the electron transfer and
      3HPPH* is quenched by oxygen to produce singlet oxygen (1O2), leading to specific
      covalent cross-linking of the nonactivated signal transducer and activator of
      transcription (STAT-3). In contrast to excitation of the HPPH moiety,
      photoexcitation of the cyanine dye unit results in a strong emission at 875 nm,
      which can be used for efficient tumor imaging. Compared to HPPH alone, the
      presence of the cyanine dye moiety in the conjugate produces a significantly
      higher uptake in tumors than in skin. Thus, the HPPH-cyanine dye conjugate can be
      used as a dual tumor imaging and photodynamic therapy agent.

PMID- 18046481
TI  - Topical applications of iron chelators in photosensitization.
AB  - Generation of the reactive oxygen species (ROS) in skin by exposure to
      ultraviolet (UV) radiation induces a number of cutaneous pathologies such as skin
      cancer, photosensitization, and photoaging among others. Skin iron catalyzes UV
      generation of ROS. Topical application of iron chelators reduces erythema,
      epidermal and dermal hypertrophy, wrinkle formation, tumour appearance. It has
      been proposed that iron chelators can be useful agents against damaging effects
      of both short- and long-term UV exposure. A better understanding of the action
      mechanisms of iron chelators, might be useful to developing effective anticancer
      and antiphotoaging cosmetic products. Iron chelators may lead to accumulation of
      protoporphyrin IX (PpIX), a strong photosensitizer. The action of iron chelators
      in skin, related to PpIX increase has not yet been thoroughly studied. Therefore,
      we have investigated the formation of PpIX in normal mouse skin after topical
      application of creams containing metal chelators. The amount and distribution of
      porphyrins formed was determined by means of non-invasive fluorescence
      spectroscopy. Deferoxamine (DF), ethylenediaminetetraacetic acid (EDTA), 1,2
      diethyl-3-hydroxypyridin-4-one (CP94), but not meso-2,3-dimercaptosuccinic acid
      (DMSA), caused increased accumulation of endogenous porphyrins in the skin.
      Fluorescence excitation and emission spectroscopy confirmed that PpIX was the
      main fluorescent species. The amount of PpIX accumulated in skin under the
      present conditions was not large enough to produce any significant erythema after
      light exposure. Further studies are needed to evaluate the role of PpIX induced
      by iron chelators used, against photoaging and cancer prevention.

PMID- 18046482
TI  - Hypericin-mediated photodynamic therapy in combination with Avastin (bevacizumab)
      improves tumor response by downregulating angiogenic proteins.
AB  - Photodynamic therapy (PDT) is a therapeutic modality in which a photosensitizer
      is locally or systemically administered followed by light irradiation of suitable
      wavelength to achieve selective tissue damage. In addition, PDT is an oxygen
      consuming reaction, that causes hypoxia mediated destruction of tumor vasculature
      that results in effective treatment. However, the hypoxic condition within tumors
      can cause stress-related release of angiogenic growth factors and cytokines and
      this inflammatory response could possibly diminish the efficacy of PDT by
      promoting tumor regrowth. In such circumstances, PDT effectiveness can be
      enhanced by combining angiogenesis inhibitors into the treatment regimen. Avastin
      (bevacizumab), a vascular endothelial growth factor (VEGF) specific monoclonal
      antibody in combination with chemotherapy is offering hope to patients with
      metastatic colorectal cancer. In this study we evaluated the combination of
      hypericin-mediated PDT and Avastin on VEGF levels as well as its effect on
      overall tumor response. Experiments were conducted on bladder carcinoma
      xenografts established subcutaneously in Balb/c nude mice. Antibody array, enzyme
      linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed
      to assess VEGF concentrations in the various treatment groups. Our results
      demonstrated that the targeted therapy by Avastin along with PDT can improve
      tumor responsiveness in bladder tumor xenografts. Immunostaining showed minimal
      expression of VEGF in tumors treated with combination therapy of PDT and Avastin.
      Angiogenic proteins e.g., angiogenin, basic fibroblast growth factor (bFGF),
      epidermal growth factor (EGF) and interleukins (IL-6 and IL-8) were also found to
      be downregulated in groups treated with combination therapy.

PMID- 18046483
TI  - Dying cells program their expedient disposal: serum amyloid P component
      upregulation in vivo and in vitro induced by photodynamic therapy of cancer.
AB  - Serum amyloid P component (SAP) is known as a prototypic acute phase reactant in
      the mouse and the protein that binds to dying cells securing their swift disposal
      by phagocytes. Treatment of solid tumors by photodynamic therapy (PDT) triggers
      SAP production in the liver of host mice, its release in the circulation and
      accumulation in PDT-targeted lesions. In the present study, mouse Lewis lung
      carcinoma (LLC) cells treated in vitro by PDT are shown to upregulate their gene
      encoding SAP. This effect was manifested following PDT treatment mediated by
      various types of photosensitizers (Photofrin, BPD, mTHPC, ALA). Generated SAP
      protein was not detected in tissue supernatants but remained localized to
      producing PDT-treated cells. The upregulation of SAP gene was observed also in
      untreated IC-21 macrophages after they were co-incubated for 4 h with PDT-treated
      LLC cells. Based on these findings, SAP that accumulates in PDT-treated tumors
      may originate from both systemic sources (released from the liver as acute phase
      reactant) and local sources; the latter could include tumor cells directly
      sustaining PDT injury and macrophages invading the tumor that become stimulated
      by signals from these affected tumor cells. Since SAP gene upregulation in LLC
      cells increased with the lethality of PDT dose used for their treatment, we
      propose that cells sensing they are inflicted with mortal injury can turn on
      molecular programs insuring not only that they die an innocuous form of death
      (apoptosis) but also that once they are dead their elimination is (facilitated by
      SAP) swift and efficient.

PMID- 18046484
TI  - Apoptotic and autophagic responses to Bcl-2 inhibition and photodamage.
AB  - Among the cellular responses to photodamage initiated by photodynamic therapy
      (PDT) are autophagy and apoptosis. While autophagy is a reversible process that
      can be both a survival and a death pathway, apoptosis is irreversible, leading
      only to cell death. In this study, we followed the fate of mouse leukemia L1210
      cells after photodamage to the endoplasmic reticulum (ER) using a porphycene
      photosensitizer, where Bcl-2 was among the PDT targets. In wild-type cells, we
      observed a rapid wave of autophagy, presumed to represent the recycling of some
      damaged organelles, followed by apoptosis. Using shRNA technology, we created a
      Bax knockdown line (L1210/Bax(-)). In the latter cell line, we found a marked
      decrease in apoptosis after photodamage or pharmacologic inactivation of Bcl-2
      function, but this did not affect PDT efficacy. Loss of viability was associated
      with a highly-vacuolated morphology consistent with autophagic cell death.
      Previous studies indicated pro-survival attributes of autophagy after low-dose
      PDT, suggesting that autophagy may be responsible for the 'shoulder' on the dose
      response curve. It appears that attempts at extensive recycling of damaged
      organelles are associated with cell death, and that this phenomenon is amplified
      when apoptosis is suppressed.

PMID- 18046485
TI  - Analyzing effects of photodynamic therapy with 5-aminolevulinic acid (ALA)
      induced protoporphyrin IX (PPIX) in urothelial cells using reverse phase protein
      arrays.
AB  - Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced
      protoporphyrin IX (PPIX) is clinically established approach for a number of
      defined applications. However, in order to optimize the therapeutic benefits of
      PDT, the specific mode of cell destruction should be better defined. Apoptosis is
      favored over necrosis for clinical practice as the latter causes more side
      effects. In the present study, we analyse PDT-induced cell death and its
      correlation to various PDT parameters (different doses applied, time after PDT
      treatment) in vitro using reverse phase protein arrays. Human urothelial cell
      lines with varying degrees of differentiation (UROtsa, RT4, RT112, J82) were
      subjected to in vitro-PDT using increasing doses of irradiation. In addition,
      positive controls for apoptosis, necrosis and un-/specific cellular damage were
      included. Cells were harvested over a specified time course, lysed and arrayed
      onto nitrocellulose-covered glass slides. The arrays were analyzed for expression
      of apoptosis-related proteins by immunohistochemistry. Analysis of caspase-3 and 
      9 expression, the activation of HIF-1alpha, Bcl2, Cox2 and the phosphorylation of
      AKT reveals signal activation due to a PDT-stimulus in correlation with the
      positive controls. Data were analyzed by unsupervised hierarchical clustering and
      depicted as a heat map revealing cell-specific patterns of pathway stimulation.
      Higher differentiated phenotypes showed a more distinct signal response in
      general and a higher apoptotic response in detail. Lower differentiated cell
      lines lost pathway regulation capabilities according to their state of
      dedifferentiation. Reverse phase protein arrays are a promising technique for
      signal pathway profiling: they exceed the range of traditional western blots by
      sensitivity, high-throughput capability, minimal sample consumption and easy
      quantification of results obtained.

PMID- 18046486
TI  - Response to ALA-based PDT in an immortalised normal breast cell line and its
      counterpart transformed with the Ras oncogene.
AB  - Aminolevulinic acid (ALA)-based photodynamic therapy (PDT) has been successfully
      employed in the treatment of certain tumours. Porphyrins endogenously generated
      from ALA induce tumour regression after illumination with light of an appropriate
      wavelength. The aim of this work was to compare porphyrin production from ALA and
      sensitivity to photodynamic treatment in a tumour/normal cell line pair. We
      employed the HB4a cell line from normal mammary luminal epithelium and its
      counterpart transfected with the oncogen H-Ras (VAL/12 Ras). After 3 h of
      exposure to ALA, HB4a-Ras cells produce a maximum of 150 ng porphyrins per 10(5)
      cells whereas HB4a produce 95 ng porphyrins per 10(5) cells. In addition, HB4a
      Ras cells show a plateau of porphyrin synthesis at 1 mM whereas HB4a porphyrins
      peak at the same concentration, and then decrease quickly. This higher porphyrin
      synthesis in the tumorigenic cell line does not lead to a higher response to the
      photodynamic treatment upon illumination. Lethal doses 50, LD(50), determined by
      MTT assay were 0.015 J cm(-2) and 0.039 J cm(-2) for HB4a and HB4a-Ras
      respectively after 3 h exposure to 1 mM ALA. The conclusion of this work is that
      a tumour cell line obtained by transfection of the Ras oncogene, although
      producing higher porphyrin synthesis from ALA, is more resistant to ALA-PDT than
      the parental non-tumour line, however the mechanism is not related to
      photosensitiser accumulation, but very likely to cell survival responses.

PMID- 18046487
TI  - Using the singlet oxygen scavenging property of carotenoid in photodynamic
      molecular beacons to minimize photodamage to non-targeted cells.
AB  - We recently introduced the concept of photodynamic molecular beacons (PMB) for
      selective control of photodynamic therapy (PDT). The PMB consists of a peptide
      linker that is sequence specific to a cancer-associated protease. A
      photosensitizer (PS) and a singlet oxygen (1O2) quencher are conjugated to the
      opposite ends of this linker. Proximity of the PS and quencher can efficiently
      inhibit 1O2 generation. In the presence of a targeted protease, the substrate
      sequence is cleaved and the PS and quencher will separate so that the PS can be
      photo-activated. There are two ways to optimize the PMB selectivity to cancer
      cells. The first is to increase the protease specificity to targeted cells and
      the second is to minimize the phototoxicity of intact (uncleaved) PMBs in non
      targeted (normal) cells. Carotenoids (CARs) are well known in nature for their
      role in quenching excited states of PS and in directly scavenging 1O2. The
      purpose of this study is to evaluate whether the CAR with dual quenching modes
      (PS excited states deactivation and 1O2 scavenging) can be used to minimize the
      photodamage of intact PMBs to non-targeted cells. Thus, we synthesized a beacon
      (PPC) with a caspase-3 cleavable peptide linking a PS and a CAR quencher. It was
      confirmed that CAR deactivates the PS excited states and also directly scavenges
      1O2. Moreover, the in vitro PDT response showed that CAR completely shuts off the
      photodynamic effect in non-targeted HepG(2) cells, while PS without CAR (control)
      remains highly potent even at a much lower (30-fold) dose.

PMID- 18046488
TI  - The effect of Tookad-mediated photodynamic ablation of the prostate gland on
      adjacent tissues--in vivo study in a canine model.
AB  - Photodynamic therapy (PDT) mediated with vascular acting photosensitizer Tookad
      (Pd-bacteriopheophorbide) was investigated as an alternative modality for
      treating prostate cancer. Photodynamic effects on the prostate gland and its
      adjacent tissues were evaluated in a canine model. Interstitial prostate PDT was
      performed by irradiating individual lobes with a cylindrical diffuser fiber at
      various drug/light doses. The sensitivity of the adjacent tissues to Tookad PDT
      was determined by directly irradiating the surface of the bladder, colon,
      abdominal muscle and pelvic plexus with a microlens fiber at various drug/light
      doses. The prostate and adjacent tissues were harvested one-week after the
      treatment and subjected to histopathological examination. PDT-induced prostate
      lesions were characterized by marked hemorrhagic necrosis. The bladder, colon,
      abdominal muscle and pelvic plexus appeared to be sensitive to PDT although the
      Tookad PDT-induced responses in these tissues were minimal compared to that of
      the prostate gland at the same dose levels. Nevertheless, the protection of the
      adjacent tissues should be taken into consideration during the total prostate
      ablation process due to their sensitivity to PDT. The sensitivity of the
      prostatic urethra is worth further investigation. Direct intraurethral
      irradiation might provide an ideal means to determine the sensitivity of the
      prostatic urethra and might lead to transurethral PDT protocols for the
      management of benign prostatic hyperplasia (BHP).

PMID- 18046489
TI  - Light fractionation does not enhance the efficacy of methyl 5-aminolevulinate
      mediated photodynamic therapy in normal mouse skin.
AB  - Previous work demonstrated that fractionated illumination using two fractions
      separated by a dark interval of 2 h, significantly enhanced the clinical efficacy
      of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA). Considering the
      increasing clinical use of methyl 5-aminolevulinate (MAL) and the expected gain
      in efficacy by light fractionation we have investigated the response to MAL-PDT
      using a single and a two-fold illumination scheme and compared that with ALA-PDT.
      Our results show that fractionated illumination does not enhance the efficacy of
      PDT using MAL as it does using ALA despite the comparable fluorescence
      intensities at the end of the first light fraction and at the start of the second
      light fraction. Only the initial rate of photobleaching was slightly greater
      during ALA-PDT although the difference was small. Previously we hypothesized that
      cells surviving the first fraction are more susceptible to the second fraction.
      Since this is not true for MAL-PDT our data suggest that the distribution of MAL
      and ALA in tissues, and therefore the site of PDT induced damage, is an important
      parameter in the mechanism underlying the 2-fold illumination scheme.

PMID- 18046490
TI  - Role of mitochondria in cell death induced by Photofrin-PDT and ursodeoxycholic
      acid by means of SLIM.
AB  - The present study was undertaken to find new ways to improve efficacy of
      photodynamic therapy (PDT). We investigated the combinatory effect of the
      photosensitizer Photofrin and ursodeoxycholic acid (UDCA). UDCA is a relatively
      non-toxic bile acid which is used inter alia as a treatment for cholestatic
      disorders and was reported to enhance PDT efficiency of two other
      photosensitizers. Since besides necrosis and autophagic processes apoptosis has
      been found to be a prominent form of cell death in response to PDT for many cells
      in culture, several appropriate tests, such as cytochrome c release, caspase
      activation and DNA fragmentation were performed. Furthermore spectral resolved
      fluorescence lifetime imaging (SLIM) was used to analyse the cellular composition
      of Photofrin and the status of the enzymes of the respiratory chain. Our
      experiments with two human hepatoblastoma cell lines revealed that the
      combination of Photofrin with UDCA significantly enhanced efficacy of PDT for
      both cell lines even though the underlying molecular mechanism for the mode of
      action of Photofrin seems to be different to some extent. In HepG2 cells cell
      death was clearly the consequence of mitochondrial disturbance as shown by
      cytochrome c release and DNA fragmentation, whereas in Huh7 cells these features
      were not observed. Other mechanisms seem to be more important in this case. One
      reason for the enhanced PDT effect when UDCA is also applied could be that UDCA
      destabilizes the mitochondrial membrane. This could be concluded from the
      fluorescence lifetime of the respiratory chain enzymes which turned out to be
      longer in the presence of UDCA in HepG2 cells, suggesting a perturbation of the
      mitochondrial membrane. The threshold at which PDT damages the mitochondrial
      membrane was therefore lower and correlated with the enhanced cytochrome c
      release observed post PDT. Thus enforced photodamage leads to a higher loss of
      cell viability.

PMID- 18046491
TI  - A study on the photodynamic properties of chlorophyll derivatives using human
      hepatocellular carcinoma cells.
AB  - Photodynamic therapy (PDT) is an alternative anticancer treatment in which direct
      tumor-cell killing results from selective accumulation of photosensitizers in the
      tumor sites and phototoxicity occurs when light-activated photosensitizers
      transfer the energy to oxygen nearby to produce singlet oxygen. The objective of
      this study was to investigate the effects of PDT using chlorophyll derivatives
      such as pheophytin a (phe a), pheophytin b (phe b), pheophorbide a (pho a) and
      pheophorbide b (pho b) as the photosensitizers, and the 660 nm light-emitting
      diodes (LEDs) irradiation on human hepatocellular carcinoma cells (HuH-7). The
      drug concentration-dependent inhibition of HuH-7 cell viability was studied under
      LEDs irradiation (10 mW cm(-2)) at radiant exposure of 5.1 and 10.2 J cm(-2) by
      MTT assay. Significant inhibition of the survival of HuH-7 cells (<10%) was
      observed when an irradiation dose of 10.2 J cm(-2) combined with the
      concentration of 0.5 microg ml(-1) of phe a, 0.125 microg ml(-1) of pho a, 0.25
      microg ml(-1) of phe b, and 0.125 microg ml(-1) of pho b were applied. The
      results from Annexin V-propidium iodide staining revealed that phe a, phe b, pho
      a and pho b could induce cell death in HuH-7 cells predominantly via a necrotic
      process. The results from immunoblot analyses exhibited that chlorophyll
      derivative-mediated PDT initiated cytochrome c release, caspase-9 and caspase-3
      activation, followed by poly ADP-ribose polymerase (PARP) cleavage. Thus,
      apoptosis also occurred in HuH-7 cells after PDT treatment, and the execution of
      the apoptotic process may be initiated from the loss of mitochondrial function.
      Our findings demonstrate that both apoptosis and necrosis can be induced in HuH-7
      cells after PDT using phe a, phe b, pho a and pho b and LEDs.

PMID- 18046492
TI  - Prevalence of plexiform neurofibroma in children and adolescents with type I
      neurofibromatosis.
AB  - OBJECTIVE: To assess prevalence of plexiform neurofibroma in children and
      adolescents with type I neurofibromatosis and its malignant potential. METHODS: A
      retrospective study was conducted through analysis of the database at Centro
      Nacional de Neurofibromatose [Brazilian Neurofibromatosis Center], collected from
      the following reference services between 1996 and 2004: Instituto de Dermatologia
      Prof. Rubem David Azulay da Santa Casa de Misericordia do Rio de Janeiro,
      Instituto de Pediatria e Puericultura Martagao Gesteira da Universidade Federal
      do Rio de Janeiro and Department of Immunology and Microbiology at Faculdade de
      Medicina de Teresopolis. RESULTS: Over that period, 104 patients aged between 1
      17 years were admitted with clinical diagnosis of type I neurofibromatosis. Of
      these, 53 were male and 51 were female, and 28 patients (15 male and 13 female)
      had plexiform neurofibroma (26.9%). Division by age group resulted in 21.42%
      (six) between 1-5 years; 35.71% (10) between 6-12 years and 42.85% (12) between
      13-17 years. Of the 104 patients, two developed a malignant peripheral nerve
      sheath tumor (1.92%). CONCLUSIONS: Plexiform neurofibromas are relatively common
      manifestations in patients with type I neurofibromatosis and may be a cause of
      significant increase in morbidity and mortality among patients. In this study, we
      conclude that frequency of plexiform neurofibroma and its malignant potential in
      the population studied is in agreement with data from the international
      literature.

PMID- 18046493
TI  - Echocardiographic abnormalities in children with obstructive breathing disorders
      during sleep.
AB  - OBJECTIVES: To assess cardiac morphology and function by means of echocardiograms
      of children with obstructed breathing while asleep. METHODS: The study enrolled
      40 children of both sexes, aged from 3 to 11 years; 30 of them had obstructed
      breathing during sleep (group I) and 10 children were healthy controls (group
      II). The two groups were similar in terms of sex, age, weight and height. The 40
      children underwent echocardiogram, viewing all four chambers during systole and
      diastole, paying special attention to the right ventricle (RV). These data were
      compared by means of Student's t test (p < 0.05). RESULTS: In group I, increased
      diameter and area of the right ventricle were observed during both systole and
      diastole. There was less variation in RV area between systole and diastole.
      Reduced left ventricle (LV) diastolic diameter was also observed, together with
      reduced ejection fraction and reduced contraction. CONCLUSIONS: The morphological
      and functional cardiac abnormalities observed in the RV and LV suggest that, in
      children, obstructed breathing during sleep can lead to cardiovascular
      repercussions. These abnormalities may expose these children to increased
      anesthetic and surgical risks.

PMID- 18046494
TI  - 'Am I going to see the next morning?' A qualitative study of patients'
      perspectives of sleep in COPD.
AB  - AIM: To investigate patients' perspectives of sleep in COPD. METHOD: Patients
      with moderate to severe COPD underwent semi-structured interviews about their
      sleep experiences. Contextual questionnaire data were collected. RESULTS: Ten
      patients were studied. Six reported bad sleep, but all described some sleep
      problems. Nocturnal anxiety and fears of breathlessness and dying were common
      features; these impacted on existing sleep problems related to exacerbations,
      medications, and habitual behaviours that can disrupt sleep. Poor sleep was
      associated with poorer health status. Patients reported a lack of support from
      their GPs and few had received advice for sleep problems. CONCLUSION: Anxiety
      about breathlessness affects the sleep experience of patients with COPD, and
      sleep quality impacts on physical and emotional functioning. Education about
      behaviours that can disrupt sleep offers potential benefits to the patient. COPD
      patients' sleep issues are complex and should be addressed at the clinical
      consultation.

PMID- 18046495
TI  - A 24-year old man with persistent progressive breathlessness: early onset COPD.
AB  - We describe the case of a 24-year old male who had been a heavy smoker since the
      age of 9 and who presented with an 8-year history of respiratory symptoms. He was
      having treatment for asthma. Spirometric studies and high-resolution computed
      tomography (HRCT) scans confirmed COPD with centrilobular emphysema. His blood
      level of alpha-1-antitrypsin was within the normal range. Early onset emphysema
      in smokers with a normal alpha-1-antitrypsin has been previously described.
      However, this case is, as far as we know, one of the youngest cases ever
      reported.

PMID- 18046496
TI  - [Correction of heel strike in a hindfoot stump not adequate for weightbearing
      following Chopart amputation. Tibiocalcaneal arthrodesis and intramedullary
      nailing].
AB  - Chopart amputation leaves a very efficient hindfoot stump allowing full
      plantigrade weightbearing, even without an artificial limb in place for short
      distances. It must be said that this presupposes that the sole is covered with
      skin originally taken from the sole of the foot and that the tread of the heel is
      correct. Imbalance of the tendons frequently causes an increasing equinovarus
      deformity, which can lead to secondary problems. We report on a 28-year-old man
      with a stump in a fixed equinovarus deformity following traumatic Chopart
      amputation. Weightbearing was not possible, and constant ulcers entailed frequent
      periods of unfitness for work, so that he expressly requested below-knee
      amputation at first. Correction of the equinovarus deformity by tibiocalcaneal
      arthrodesis using intramedullary nailing led to lasting healing of the skin and
      the possibility of full weightbearing.

PMID- 18046497
TI  - Non-migratory breeding by isolated green sea turtles (Chelonia mydas) in the
      Indian Ocean: biological and conservation implications.
AB  - Green sea turtles (Chelonia mydas) are renowned for their long-distance
      migrations but have less fame for short-distance migrations or non-migratory
      behavior. We present satellite telemetric evidence from Cocos (Keeling) Islands,
      Indian Ocean for the first predominantly non-migratory green sea turtle (C.
      mydas) population. The mean migration distance from the nesting beach to the
      foraging grounds was 35.5 km with a maximum mean transit time of 3.4 days. The
      behavior of this population has major implications for our general understanding
      of green turtle behavior and their life cycle and for conservation. Firstly,
      these results indicate a level of juvenile or adult non-breeding homing behavior
      from the open ocean to foraging grounds adjacent to their natal nesting beach.
      Secondly, a non-migratory breeding phase reduces the consumption of reproductive
      energy utilized, potentially resulting in higher fecundity for this population.
      Thirdly, the close proximity of the nesting and foraging habitats allows for
      uniformity in management and conservation strategies rarely possible for wide
      ranging green turtle populations.

PMID- 18046498
TI  - Mercury and trace elements in crayfish from northern california.
AB  - We collected two species of crayfish, Pacifastacus leniusculus and Procambarus
      clarkii, from Cache and Putah Creeks, California, and analyzed them for mercury
      and trace elements. Trace elements were higher in carcasses in 40 cases, higher
      in tails in 5 cases, and not different in 35 cases; no concentration exceeded
      levels considered harmful. Mercury concentrations were similar among sites, with
      no overall sex or species effect in tails. Mercury and methylmercury
      concentrations were higher in tails at all sites. Methylmercury concentrations in
      crayfish tails (0.156-0.256 microg/g) exceeded concentrations reported in health
      advisories for consumption of fish and crayfish from these watersheds.

PMID- 18046499
TI  - Three novel mutations of the PHEX gene in three Chinese families with X-linked
      dominant hypophosphatemic rickets.
AB  - X-linked dominant hypophosphatemia (XLH, OMIM307800), the most prevalent form of
      inherited rickets in humans, is a dominant disorder of phosphate homeostasis
      characterized by growth retardation, rachitic and osteomalacic bone disease,
      hypophosphatemia, and renal phosphate wasting. The gene responsible for XLH was
      identified by positional cloning and designated PHEX (formerly PEX) to depict a
      phosphate-regulating gene homologous with endopeptidases on the X chromosome.
      Recently, extensive mutation analysis of the PHEX gene has revealed a wide
      variety of gene defects in XLH. The ethnic distribution of the mutations is very
      widespread but only a few mutations in Chinese have been reported. To analyze the
      molecular basis in three unrelated Chinese families with XLH, we determined the
      nucleotide sequence of the PHEX gene and fibroblast growth factor 23 (FGF23) gene
      of affected members. The serum FGF23 concentrations of these patients with XLH
      were also measured. Three different novel mutations were observed in these three
      families: one deletion mutation c.264delG causing p.W88 X; one missense mutation
      c.1673C>G causing p.P558A; one nonsense mutation c.1809G>A causing p.W603 X.
      Serum concentration of FGF23 in XLH patients of these three families was
      significantly higher than normal. The results suggest that PHEX gene mutations
      were responsible for XLH in these patients and these mutations may contribute to
      a higher serum FGF23 level.

PMID- 18046500
TI  - Endothelial nitric oxide synthase gene [G894T] polymorphism as a possible risk
      factor in aneurysmal subarachnoid haemorrhage.
AB  - BACKGROUND: The exact aetiology, growth and rupture of intracranial aneurysms is
      unclear. In this study we investigated a possible association between
      intracranial aneurysm rupture and polymorphism of the endothelial nitric oxide
      synthase gene G894T. METHODS: Endothelial nitric oxide synthase gene polymorphism
      of 53 patients with ruptured intracranial aneurysms and 60 control subjects were
      analysed by the polymerase chain reaction-restriction fragment length
      polymorphism technique. The genotype distribution and allele frequencies of
      endothelial nitric oxide synthase gene polymorphism in patients with ruptured
      intracranial aneurysm and healthy subjects were compared. FINDINGS: The
      homozygous (TT) genotype frequency was significantly higher in patients with
      ruptured intracranial aneurysms. It was also found that the presence of eNOS
      894TT genotype was significantly associated with the risk of intracranial
      aneurysm rupture (p < 0.05). CONCLUSION: Polymorphism in exon 7 of the
      endothelial nitric oxide synthase gene G894T seems to be a possible risk factor
      for intracranial aneurysm rupture.

PMID- 18046501
TI  - Up-regulation of vimentin expression in low-density malignant glioma cells as
      immediate and late effects under irradiation and temozolomide treatment.
AB  - Nervous system tumors are one of the leading causes of cancer related death.
      Specific mechanisms facilitating the invasive behavior of gliomas remain obscure.
      Advanced simulation models of the in vivo response to therapy conditions should
      potentially improve malignant glioma treatment. Expressional profiling of
      vimentin--one of reliable pro-invasive tumor makers--in those simulation models
      was the goal of this study, in order to estimate a pro-invasive response of
      surviving malignant glioma cells under clinically relevant therapeutic
      conditions. Human U87-MG malignant glioma cells were used. These cells are
      characterized by the wild p53-phenotype, which is relevant for the majority of
      primary malignant glioblastomas. Experimental design foresaw the cells to undergo
      either irradiation or chemo-treatment with temozolomide alone, or combined
      treatment. Expression profiling of vimentin was performed by quantitative "Real
      Time"-PCR under all treatment conditions simulating diverse tumor regions. Here
      we demonstrated that vimentin expression patterns in human malignant glioma cells
      strongly depend on cellular density, algorithms of drug delivery and chemo/radio
      treatment. Substantial differences were recognized between immediate and late
      therapy effects. Significant increase in vimentin expression levels was detected
      particularly in low-density cell cultures under durable treatment with constant
      concentration levels of temezolomide. Simulation of variable intratumoral
      regional conditions (central intratumoral regions vs. disseminated malignant
      cells in peripheral regions) demonstrated differential response of vimentin
      expression in malignant glioma cell cultures treated under clinically relevant
      conditions. Slight ebbing of expression levels as late effects of the treatment
      in confluent cultures may correspond to necrotic processes clinically observed in
      central intratumoral regions. Contrary, in disseminated malignant cells of
      peripheral regions therapy resulted in vimentin-inducing effects. This is in
      agreement with the clinical observations of an increased aggressiveness and
      malignancy grade of post-operatively chemo/radio-treated malignant gliomas.

PMID- 18046502
TI  - Inducible heat shock protein 70 and its role in preconditioning and exercise.
AB  - Heat shock proteins (Hsp) are well known to be expressed in response to a range
      of cellular stresses. They are known to convey protection against protein
      denaturation and a subsequent immediate stress. Inducible heat shock protein 70
      (Hsp70) is among the most studied of these stress proteins and its role and
      function are discussed here in terms of thermal and in particular exercise
      preconditioning. Preconditioning has been shown to confer cellular protection via
      expression Hsp, which may be of benefit in preventing protein damage following
      subsequent periods of exercise. Many studies have used animal models to gather
      data on Hsp70 and these and the most recent human studies are discussed.

PMID- 18046503
TI  - Comprehensive assessment of P21 polymorphisms and lung cancer risk.
AB  - The purpose of this study is to comprehensively evaluate potential functional
      polymorphisms in the P21 gene in relation to the risk of lung cancer. We first
      determined the frequencies of P21 polymorphisms in 27 healthy Koreans, and then
      examined three polymorphisms (-2266G > A, S31R, and IVS2 + 16G > C), based on
      their frequencies and haplotype-tagging status, in a case-control study.
      Individuals with at least one -2266A allele were at a significantly decreased
      risk of lung cancer compared with those harboring the -2266 GG genotype [adjusted
      odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.53-0.95, P = 0.02). The
      haplotypes (ht2-4) carrying 31R or IVS2 + 16C alleles were associated with a
      significantly decreased risk of lung cancer compared with the haplotype 31S/IVS2
      + 16G, which carried wild-type alleles at both loci (adjusted OR = 0.65, 95% CI =
      0.50-0.83, P = 0.007)]. When the -2266A allele and ht2-4 were considered to be
      protective alleles, the risk of lung cancer decreased in a dose-dependent manner
      as the number of protective alleles increased (P = 0.0002). These results suggest
      that a combined analysis of these three P21 polymorphisms might better predict
      the risk of lung cancer than the analysis of a single polymorphism.

PMID- 18046504
TI  - Glucose-6-phosphate dehydrogenase mutations in Mon and Burmese of southern
      Myanmar.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in
      Southeast Asians. G6PD mutations are associated with specific ethnic groups in
      Southeast Asia. Mon is a minority ethnic group in Myanmar, which speaks Monic, a
      distinct language of Mon-Khmer classification. We studied G6PD mutations in Mon
      and Burmese males of southern Myanmar who migrated to Thailand in Samutsakhon
      province. G6PD deficiency was identified in 19 (12%) of 162 Mon males and 17
      (10%) of 178 Burmese males, and then assayed for G6PD mutations. Among 19 G6PD
      deficient Mons, 12 were G6PD Mahidol; one case each was G6PD Jammu (871G > A; nt
      1311C), G6PD Kaiping (1388G > A), G6PD Mediterranean (563C > T), a novel mutation
      94(C > G); and three remain unidentified. Among 17 G6PD-deficient Burmese, 12
      were G6PD Mahidol; one each was G6PD Coimbra (592C > T), G6PD Kerala-Kalyan (949G
      > A), and G6PD Valladolid (406C > T); and two remain unidentified. G6PD Mahidol
      (487G > A) is the most common mutation among Mons and Burmese. All G6PD deficient
      Mon and Burmese, except for a person with G6PD Valladolid, shared the same
      haplotype nt93T, nt1311C. Despite a similar language root with Cambodian's Khmer
      language, our study suggests that Mon people share a common ancestry with Burmese
      rather than Cambodians.

PMID- 18046505
TI  - Adhesion of fluid vesicles at chemically structured substrates.
AB  - The adhesion of fluid vesicles at chemically structured substrates is studied
      theoretically via Monte Carlo simulations. The substrate surface is planar and
      repels the vesicle membrane apart from a single surface domain gamma , which
      strongly attracts this membrane. If the vesicle is larger than the attractive
      gamma domain, the spreading of the vesicle onto the substrate is restricted by
      the size of this surface domain. Once the contact line of the adhering vesicle
      has reached the boundaries of the gamma domain, further deflation of the vesicle
      leads to a regime of low membrane tension with pronounced shape fluctuations,
      which are now governed by the bending rigidity. For a circular gamma domain and a
      small bending rigidity, the membrane oscillates strongly around an average
      spherical cap shape. If such a vesicle is deflated, the contact area increases or
      decreases with increasing osmotic pressure, depending on the relative size of the
      vesicle and the circular gamma domain. The lateral localization of the vesicle's
      center of mass by such a domain is optimal for a certain domain radius, which is
      found to be rather independent of adhesion strength and bending rigidity. For
      vesicles adhering to stripe-shaped surface domains, the width of the contact area
      perpendicular to the stripe varies nonmonotonically with the adhesion strength.

PMID- 18046506
TI  - Philip S. Magee: a life in QSAR.
AB  - A brief account of the career of Philip S. Magee, a distinguished member of the
      QSAR community.

PMID- 18046507
TI  - Distinct heat-shock element arrangements that mediate the heat shock, but not the
      late-embryogenesis induction of small heat-shock proteins, correlate with
      promoter activation in root-knot nematode feeding cells.
AB  - Genes coding small heat-shock proteins (sHSPs) show distinct behaviours with
      respect to environmental and developmental signals. Their transcriptional
      regulation depends on particular combinations of heat stress cis-elements (heat
      shock elements; HSEs) but many aspects regarding their regulation remain unclear.
      Cyst and root-knot nematodes induce, in the roots of infected plants, the
      differentiation of special feeding cells with high metabolic activity (syncytia
      and giant cells, respectively), a process accompanied by extensive gene
      expression changes. The Hahsp17.7G4 (G4) promoter was active in giant cells and
      its HSE arrangements were crucial for this activation. In the present work, we
      provide further basis to associate giant cell expression with the heat-shock
      response of this gene class, by analysing additional promoters. The Hahsp17.6G1
      (G1) promoter, not induced by heat shock, was silent in giant cells, while
      Hahsp18.6G2 (G2), which responds to heat shock, was specifically induced in giant
      cells. In addition, a mutated Hahsp17.7G4 promoter version (G4MutP) with a strong
      heat-shock induction was also induced in giant cells. The responses of the
      different promoters correlated with distinct HSE configurations, which might have
      implications on differential trans-activation. Furthermore, the shortest giant
      cell and heat-shock-inducible sHSP promoter version analysed in tobacco (-83pb
      Hahsp17.7G4) fully maintained its expression profile in Arabidopsis. Cyst
      nematodes did not induce the Hahsp17.7G4 promoter, revealing additional
      specificity in the nematode response. These findings, together with the fact that
      the class I sHSP products of endogenous genes accumulated specifically in tobacco
      giant cells, support the idea that these nematode-induced giant cells represent a
      transcriptional state very similar to that produced by heat shock regarding this
      class of genes. The high metabolic rate of giant cells may result in unfolded
      proteins requiring class I sHSPs as chaperones, which might, somehow, mimic heat
      shock and/or other stress responses.

PMID- 18046508
TI  - Titration of repeat-induced point mutation (RIP) by chromosome segment
      duplications in Neurospora crassa.
AB  - Repeat-induced point mutation (RIP) is a hypermutational process that alters
      duplicated DNA sequences in Neurospora crassa. In previous studies, five of six
      large ( > 100 kb) chromosome segment duplications (Dp's) examined were shown to
      dominantly suppress RIP in smaller (< 5 kb) duplications. The suppressor
      duplications were > 270 kb, whereas the lone non-suppressor duplication was
      approximately 117 kb. We have now screened another 33 duplications and found 29
      more suppressors and four more non-suppressors. All 22 suppressor duplications
      whose size could be estimated were > 270 kb, whereas two newly identified non
      suppressor duplications examined were 140-154 kb. RIP was suppressed in a subset
      of crosses heterozygous for more than one ordinarily non-suppressor duplication.
      These results strengthen the hypothesis that large duplications titrate out the
      RIP machinery and suggest the "equivalence point" for the titration is close to
      300 kb.

PMID- 18046509
TI  - Microsatellite markers reveal high genetic diversity in date palm (Phoenix
      dactylifera L.) germplasm from Sudan.
AB  - Genetic diversity in date palm germplasm from Sudan representing 37 female and 23
      male accessions was investigated using 16 loci of microsatellite (SSR) primers.
      Eight female accessions from Morocco were included as reference material. The
      tested SSR markers showed a high level of polymorphism. A total of 343 alleles
      were detected at the 16 loci. The number of alleles per marker ranged from 14 to
      44 with an average of 21.4 per locus. A high level of expected heterozygosity was
      observed among Sudan cultivars (0.841), Morocco cultivars (0.820) and male
      accessions (0.799). The results indicate that the genetic groups of the Sudan
      cultivars and/or males do not follow a clear geographic pattern. However, the
      morocco group showed significant differentiation in relation to the Sudan groups,
      as measured by F (ST) values and genetic distances. The effect of the methods of
      pollination and cultivar selection on the genetic structure was clearly detected
      by the weak clustering association that was observed for the majority of
      accessions originating from Sudan and Morocco as well. This suggests the need for
      further investigation on the genetic diversity of Sudanese date palm germplasm. A
      deeper insight will be revealed by a detailed analysis of populations originating
      from different geographic locations.

PMID- 18046510
TI  - Mutation rate and genome reduction in endosymbiotic and free-living bacteria.
AB  - Genome reduction has been considered the hallmark of endosymbiotic bacteria, such
      as endocellular mutualists or obligatory pathogens until it was found exactly the
      same in several free-living bacteria. In endosymbiotic bacteria genome reduction
      is mainly attributed to degenerative processes due to small population size.
      These cannot affect the free-living bacteria with reduced genomes because they
      are known to have very large population sizes. It has been proposed that
      selection for simplification drove genome reduction in these free-living
      bacteria. For at least one of them (Prochlorococcus), genome reduction is
      associated with accelerated evolution and we suggest an alternative hypothesis
      based on increase in mutation rate as the primary cause of genome reduction in
      free-living bacteria.

PMID- 18046511
TI  - Metastasis signatures: genes regulating tumor-microenvironment interactions
      predict metastatic behavior.
AB  - The possibility of predicting clinical outcome of cancer patients through the
      analysis of gene expression profiles in the primary tumor is a kind of
      ideological revolution as the multistep carcinogenesis model postulates that the
      proportion of cells within the primary tumor that actually acquire metastasis
      driving mutation(s) is small; too small to leave its imprint on the gene
      expression profile. The data collected to date have brought a new paradigm to
      reality in the metastasis field: metastasis must at least in part rely on
      mutations and/or gene regulation events present in the majority of cells which
      constitute the primary tumor mass. By analyses of differential expression of
      primary tumors versus metastases or by functional analyses of putative metastasis
      genes in experimental metastasis, many metastasis-associated gene expression
      events have been identified that correlate with the development of metastases.
      Among genes "favoring" metastasis, we find many molecules that are expressed not
      by the tumor cell itself but by the cells of the microenvironment, as well as
      genes over-expressed in the primary tumor that have a principle role in mediating
      tumor-host interactions. Here we review these concepts and advance hypotheses on
      how gene expression of the primary tumor and the microenvironment can favor the
      spread of the metastasis seeds and how this knowledge can provide tools to
      secondary prevention.

PMID- 18046512
TI  - Anti-inflammatory effect of alpha, beta-Amyrin, a pentacyclic triterpene from
      Protium heptaphyllum in rat model of acute periodontitis.
AB  - This study was aimed to evaluate the anti-inflammatory potential of triterpene
      alpha, beta-amyrin in rats on acute phase periodontitis. Periodontitis was
      induced by ligature placement around the maxillary right second molar tooth. Rats
      (n = 8/group) were pretreated with alpha, beta-amyrin (5 and 10 mg/kg, p. o.),
      two hours before the induction of periodontal inflammation. Sham-operated and
      positive controls (lumiracoxib and dexamethasone) were included. Six hours later,
      plasma levels of TNF-alpha were analysed. Rats were sacrificed at 24 h, and the
      gingival tissue analysed for myeloperoxidase (MPO) and thiobarbituric acid
      reactive substances (TBARS), as measures of neutrophil influx and lipid
      peroxidation, respectively alpha, beta-Amyrin as well as dexamethasone
      significantly inhibited the periodontitis-associated increases of TNF-alpha, and
      the gingival MPO and TBARS. alpha, beta-Amyrin effect was more prominent at 5
      mg/kg. Lumiracoxib manifested varied influence on the studied parameters. These
      results provide evidence to show that alpha, beta-Amyrin retards acute
      inflammation in rat model of periodontitis and warrant further study on its
      efficacy to prevent chronic periodontitis-associated bone loss.

PMID- 18046514
TI  - Analgesic, anti-inflammatory and hypoglycaemic effects of Securidaca
      longepedunculata (Fresen.) [Polygalaceae] root-bark aqueous extract.
AB  - The present study was undertaken to investigate the analgesic, anti-inflammatory
      and hypoglycaemic properties of Securidaca longepedunculata (Fresen.) root-bark
      aqueous extract (SLE) in mice and rats. The analgesic effect of SLE was evaluated
      by 'hot-plate' and 'acetic acid' analgesic test methods in mice; while its anti
      inflammatory and hypoglycaemic effects were examined in rats, using fresh egg
      albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes mellitus
      models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and chlorpropamide
      (250 mg/kg) were used as reference drugs for comparison. SLE (50-800 mg/kg i. p.)
      produced dose-dependent, significant (p < 0.05-0.001) analgesic effects against
      thermally- and chemically-induced nociceptive pain in mice. The plant's extract
      (SLE, 50-800 mg/kg p. o.) also dose-dependently and significantly inhibited (p <
      0.05-0.001) fresh egg albumin-induced acute inflammation, and caused significant
      hypoglycaemia (p < 0.05-0.001) in normal (normoglycaemic) and STZ-treated
      diabetic (hyperglycaemic) rats. The results of this experimental animal study
      indicate that S. longepedunculata root-bark aqueous extract (SLE) possesses
      analgesic, anti-inflammatory and hypoglycaemic properties. These findings lend
      pharmacological credence to the anecdotal, folkloric and ethnomedical uses of S.
      longepedunculata root-bark in the treatment, management and/or control of
      painful, arthritic, inflammatory conditions, as well as in the management and/or
      control of type 2 diabetes mellitus in some rural communities of South Africa.

PMID- 18046513
TI  - Gastric secretion, proinflammatory cytokines and epidermal growth factor (EGF) in
      the delayed healing of lingual and gastric ulcerations by testosterone.
AB  - Hormonal fluctuations are known to predispose ulceration of the upper
      gastrointestinal tract, but to date no comparative study of their effects on the
      healing of pre-existing ulcers in the oral cavity and stomach has been made. We
      studied the effects of depletion of testosterone and of EGF on the healing of
      acetic acid-induced ulcers using rats having undergone bilateral orchidectomy
      and/or salivectomy respectively. We measured alterations in gastric acid
      secretion and blood flow at ulcer margins, as well as plasma levels of
      testosterone, gastrin and the proinflammatory cytokines IL-1 beta and TNF-alpha.
      Testosterone (0.01-10 mg/kg/day i. m.) dose-dependently delayed oral and gastric
      ulcer healing. When applied in an optimal dose of 1 mg/kg/day, this hormone
      significantly raised gastric acid secretion and plasma IL-1 beta and TNF-alpha
      levels. Attenuation of plasma testosterone levels via bilateral orchidectomy
      inhibited gastric acid secretion and accelerated the healing of oral and gastric
      ulcers, while increasing plasma gastrin levels and these effects were reversed by
      testosterone. Salivectomy raised plasma testosterone levels, and delayed oral and
      gastric ulcer healing. Treatment of salivectomised animals with testosterone
      further inhibited ulcer healing, and this effect was counteracted by EGF. We
      propose that testosterone delays ulcer healing via a fall in blood flow at the
      ulcer margin, a rise in plasma levels of IL-1 beta and TNF-alpha and, in the case
      of gastric ulcers, an increase in gastric acid secretion. EGF released from the
      salivary glands plays an important role in limitation of the deleterious effects
      of testosterone on ulcer healing.

PMID- 18046515
TI  - Decompressive hemicraniectomy and durotomy for malignant middle cerebral artery
      infarction.
AB  - The high early case fatality among patients with massive hemispheric strokes
      calls for effective treatments. Release of the restriction created by the dura
      mater and bony skull to allow the infarcted brain tissue to swell has been
      successfully adopted by some while considered controversial by others. A recent
      pooled analysis provides estimates for the efficacy of decompressive surgery.
      Further analyses of current trial data suggest that in particular patient age and
      timing of surgery determine outcome. Nonetheless, in order to guide the
      management of individual patients, carefully adjusted medical care, ongoing
      futility analysis, and simultaneous caregiver meetings should be conducted to
      reach a joint decision addressing any ethical concerns. In conclusion,
      decompressive surgery increases the probability of survival but produces patients
      with moderate or moderately severe disability (albeit not severe disability).
      Currently, the decision to perform decompressive surgery should remain an
      individual one in each and every patient.

PMID- 18046516
TI  - Neuroscience leading the way: reviews cascade by the INCF.

PMID- 18046517
TI  - Management of patients on long-term oral anticoagulant therapy undergoing
      elective surgery: survey of the clinical practice in the Italian anticoagulation
      clinics.
AB  - In the perioperative management of patients on long-term oral anticoagulant (OAC)
      therapy the problem is balancing the thromboembolic (TER) and the haemorrhagic
      risk (HR) in the perioperative period. The Federazione Centri per la diagnosi
      della trombosi e la Sorveglianza delle terapie Antitrombotiche (FCSA) activated
      an online registry from November 2001 to August 2003 in order to collect
      information on the management of these patients in Italy. Four hundred and eleven
      patients, undergoing elective major (18%) and minor surgery (82%), from 7
      centres, were registered. Three hundred and ninety-nine out of 411 patients
      received LMWH either once a day (310 patients) or twice a day (89 patients)
      during OAC therapy discontinuation. Two thromboembolic (0.48%) and 16 bleeding
      events (7 major; 1.7%) were reported. Notwithstanding the lower doses of heparin
      (54.3 U/kg o.d. and 64.4 U/kg b.i.d.), the thromboembolic complications are in
      line with those reported in the literature. The data of this study suggest that
      the intervention with LMWH may be relevant only in the high-risk patients as
      already proposed by others.

PMID- 18046519
TI  - [Subsonic low frequency sound--a topic for the environmentally related health
      protection? Report of the commission "Methods and Quality Assurance in
      Environmental Medicine].

PMID- 18046518
TI  - Isolation and characterization of antioxidation enzymes from cells of zedoary
      (Curcuma zedoaria Roscoe) cultured in a 5-l bioreactor.
AB  - In this study, a cell suspension culture system for zedoary (Curcuma zedoaria
      Roscoe) was developed, using 50 g/l of fresh weight inoculum in a batch culture.
      The highest cell biomass obtained from a 5-l bioreactor equipped with three
      impellers after 14 days of culture was utilized to extract secondary metabolites
      (essential oil and curcumin) and determine the activities of antioxidant enzymes
      (peroxidase, superoxide dismutase, and catalase). For essential oil and curcumin,
      zedoary extracts were recovered via a variety of methods: steam distillation,
      volatile solvents, and Soxhlet. After 14 days of culture using volatile solvents,
      the optimal yield of essential oil (1.78%) was obtained when using petroleum
      ether at 40 degrees C in 6 h of extraction, and the best curcumin yield (9.69%)
      was obtained at 60 degrees C in 6 h via extraction with 90% ethanol. The
      activities of antioxidant enzymes from zedoary cells were also assessed. The
      specific activities of peroxidase, superoxide-dismutase, and catalase reached
      maximum values of 0.63 U/mg of protein, 16.60 U/mg of protein, and 19.59 U/mg of
      protein after 14 days of culture, respectively.

PMID- 18046520
TI  - [Gene therapy of SCID-X1].
AB  - X-linked severe combined immunodeficiency (SCID-X1) is an inherited disease
      caused by inactivating mutations in the gene encoding the interleukin 2 receptor
      common gamma chain (IL2RG), which is located on the X-chromosome. Affected boys
      fail to develop two major effector cell types of the immune system (T cells and
      NK cells) and suffer from a functional B cell defect. Although drugs such as
      antibiotics can offer partial protection, the boys normally die in the first year
      of life in the absence of a curative therapy. For a third of the children, bone
      marrow transplantation from a fully matched donor is available and can cure the
      disease without major side effects. Mismatched bone marrow transplantation,
      however, is complicated by severe and potentially lethal side effects. Over the
      past decade, scientists worldwide have developed new treatments by introducing a
      correct copy of the IL2RG-cDNA. Gene therapy was highly effective when applied in
      young children. However, in a few patients the IL2RG-gene vector has
      unfortunately caused leukaemia. Activation of cellular proto-oncogenes by
      accidental integration of the gene vector has been identified as the underlying
      mechanism. In future clinical trials, improved vector technology in combination
      with other protocol modifications may reduce the risk of this side effect.

PMID- 18046521
TI  - Left circumflex coronary artery fistula to the superior vena cava: assessment of
      the exact anatomy by multidetector CT.
AB  - A 62-year-old woman with mild dyspnea on exertion underwent coronary angiography.
      A large fistula of the left circumflex artery was found but the exit site of this
      unusual anomaly could not be established. Contrast-enhanced multidetector
      computed tomography of the coronary arteries was performed which allowed clear
      identification of the drainage of the fistula into the superior vena cava.

PMID- 18046522
TI  - Evaluation of the dedicated Frontier coronary bifurcation stent: A matched pair
      analysis with drug-eluting and bare metal stents.
AB  - Treatment of coronary bifurcation lesions (CBL) remains challenging. This study
      sought to evaluate a novel dedicated stent system (Frontier stent) by
      angiographic and clinical comparison with the provisional T-stenting technique
      using drug-eluting (DES) and bare metal stents (BMS). The study group comprised
      105 CBL in 105 patients. 35 consecutive CBL were treated with the Frontier
      system. The control group of 70 CBL (35 DES, 35 BMS) was pair matched with the
      former group stratified by the type of CBL (Medina classification) and the
      reference diameter of the main branch (MB). Clinical, procedural, and
      quantitative angiographic data (QCA) were obtained in all patients. A follow-up
      angiography 6 +/- 2-month post-index intervention was performed in 84/105 (80%)
      patients, clinical 6-month follow-up was available in all patients (100%). All
      Frontier stent procedures were clinically and angiographically successful. Post
      procedural QCA analysis of the MB and the side branches revealed comparable
      minimal lumen diameters (MLDs) between groups. Moreover, contrast use and
      radiation exposure were not different between groups. DES use, however, was
      associated with a significantly lower late lumen (LL) loss in the main and the
      side branch as compared to the Frontier stent and BMS group. Likewise, MACE rates
      were lowest in the DES group (6%, P < 0.05 vs. BMS) as compared to the Frontier
      stent (9%) and the BMS group (16%). The Frontier stent accomplishes treatment of
      CBL with excellent acute clinical, procedural, and angiographic results.
      Provisional T-stenting using DES provides superior clinical and angiographic long
      term results as compared to BMS and Frontier stents. The results of next
      generation CBL systems combining a dedicated specific CBL design with DES
      surfaces are to be awaited.

PMID- 18046523
TI  - Sirolimus-eluting stents in the treatment of chronic total coronary occlusions:
      results from the prospective multi-center German Cypher Stent Registry.
AB  - OBJECTIVES: We assessed the effectiveness and safety of the sirolimus-eluting
      stent (SES) in the treatment of chronic total coronary occlusions. BACKGROUND:
      Chronic total occlusions (CTO) of coronary vessels have an unacceptable high
      restenosis rate of approximately 50% after stenting. Few data exist about the
      performance of drug eluting stents (DES) in the treatment of CTO. METHODS: All
      coronary interventions using the Cypher stent performed at 122 centers engaged in
      the German Cypher registry between April 2002 and December 2004 were analyzed; a
      total of 5,344 patients; 374 with and 4,970 without CTO were compared. RESULTS:
      There was no significant difference between both groups regarding demographics,
      coronary status and left ventricular function. Patients in the CTO group had a
      higher level of angina symptoms, the coronary lesions were more complex and the
      stents used were smaller and longer than in the No-CTO group. The In-hospital
      outcome was similar in both groups, with importantly no difference regarding
      mortality and complications. Stenting was as successful in the CTO as in the No
      CTO group; during a follow-up of 6.6 months we found no significant difference
      regarding the rate of mortality, complications, and revascularization between
      both groups. CONCLUSIONS: Implantation of the Cypher stent reduces the restenosis
      rate and seems to be a safe and effective tool for the treatment of chronic total
      coronary occlusions.

PMID- 18046525
TI  - Transcatheter recanalization of acutely occluded modified systemic to pulmonary
      artery shunts in infancy.
AB  - BACKGROUND: There are few data on successful recanalization of acutely occluded
      modified aortopulmonary shunts in infants in whom the major component of
      pulmonary flow is shunt-dependent. PATIENTS AND METHODS: Seven infants (age range
      6 days to 7 months) with modified (polytetrafluoroethylene) aortopulmonary shunts
      (central shunt n = 6, modified Blalock-Taussig shunt n = 1), in whom acute shunt
      occlusion was documented following surgery (interval from shunt surgery 2-6 days)
      underwent emergency cardiac catheterization with a view to reopening the shunt.
      Anterograde right ventricle to pulmonary artery flow was present in three
      patient; two other had additional aortopulmonary collateral vessels, and
      intravenous prostaglandin E (PGE1) infusion was restarted in three infants to
      achieve or maintain ductal patency. All occluded shunts could be crossed with a
      4F endhole catheter and various guidewire combinations. Balloon dilation was
      performed using a balloon with the same nominal diameter as the shunt (5 or 6
      mm). RESULTS: All shunts were successfully recanalized. Two infants with
      recurrent cyanotic episodes underwent stent implantation in the right ventricular
      outflow tract (RVOT) during the same procedure. One infant required shunt
      revision 24 h following balloon angioplasty, during which a small clot was
      evacuated from the distal end of the shunt. An immediate improvement in oxygen
      saturation could be documented in all patients. In the remaining six infants,
      shunt patency was confirmed at follow-up, until further definitive repair. One
      infant died of non-cardiac causes, while awaiting definitive repair. CONCLUSIONS:
      This small series demonstrates that acutely occluded shunts can be successfully
      recanalized, and that patency can be maintained until further definitive surgery
      in the majority of infants.

PMID- 18046524
TI  - Guideline adherence for pharmacotherapy of chronic systolic heart failure in
      general practice: a closer look on evidence-based therapy.
AB  - BACKGROUND: There is robust evidence for effective pharmacotherapy of chronic
      (systolic) heart failure (CHF) which has led to the creation of guidelines, but
      many surveys evaluating CHF treatment show an under-utilisation of relevant
      drugs, while setting and patient population appear to be crucial for adequate
      appraisal of treatment patterns. AIMS: To evaluate the guideline adherence (GA)
      of general practitioners (GPs) in a well-defined patient population with CHF in
      primary care (PC). METHODS: A cross-sectional analysis was performed with the
      data of 167 patients enrolled in 37 GP practices (Germany) with documented left
      ventricular systolic dysfunction (LVEF: 33.3 +/- 6.9%). GA was assessed as usual
      (prescribing "yes" or "no"), through evaluation of target dosing, while adjusting
      for potential clinical contraindications, and through a modified Guideline
      Adherence Indicator-3 (mGAI-3), which assesses three relevant groups of
      substances according to New York Heart Association (NYHA) functional class: ACE
      Inhibitors (ACE-I) or angiotensin receptor blockers (ARB), beta-blockers (BB) and
      aldosterone-antagonists (AA). RESULTS: Prescription rates for ACE-I/ARB, BB or
      both were 80%, 75% and 62%, respectively. The proportion of target doses reached
      for ACE-I was 16%, for BB only 8%. When adjusted for potential (mainly relative)
      contraindications (COPD, heart rate <60/min, hypotension, hyperkalaemia and renal
      dysfunction), the percentage of target doses reached increased to 49% for ACE
      I/ARBs and 46% for BB. Application of the mGAI-3 showed moderate to perfect GA
      for usual assessment, proportion of target dose reached and adjusted in 83%, 16%
      and 55% of the patients, respectively. CONCLUSION: In the context of this patient
      and doctor setting, life-saving treatment was provided above average when
      assessed by usual criteria. The application of additional criteria showed further
      room for improvement. Future interventions aiming at optimisation should be
      tailored to the needs of doctors and patients likewise.

PMID- 18046526
TI  - Mechanism of action of the new anti-ischemia drug ranolazine.
AB  - Myocardial ischemia is associated with reduced ATP fluxes and decreased energy
      supply resulting in disturbances of intracellular ion homeostasis in cardiac
      myocytes. In the recent years, increased persistent (late) sodium current was
      suggested to contribute to disturbed ion homeostasis by elevating intracellular
      sodium concentration with subsequent elevation of intracellular calcium. The new
      anti-ischemia drug ranolazine, a specific inhibitor of late sodium current,
      reduces sodium overload and hence ameliorates disturbed ion homeostasis. This is
      associated with symptomatic improvement of angina in patients. Moreover,
      ranolazine was shown to exhibit anti-arrhythmic effects. In the present article,
      we review the relevant pathophysiological concepts for the role of late sodium
      inhibition and summarize the most recent data from basic as well as clinical
      studies.

PMID- 18046527
TI  - Troponin level and efficacy of abciximab in patients with acute coronary
      syndromes undergoing early intervention after clopidogrel pretreatment.
AB  - OBJECTIVE: We investigated how does troponin level (TnT) affect the benefit
      achieved by abciximab in patients with acute coronary syndromes (ACS) undergoing
      percutaneous coronary intervention (PCI) after pretreatment with a high loading
      dose of clopidogrel. METHODS: The Intracoronary Stenting and Antithrombotic
      Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) trial included
      2,022 patients with non-ST elevation ACS undergoing PCI who were randomized to
      abciximab or placebo after pretreatment with 600 mg of clopidogrel. The patients
      were divided into groups with elevated TnT level (n = 1,049) and no elevated TnT
      level (n = 973). The primary end point of the trial was the composite of death,
      myocardial infarction and urgent reintervention at 30 days. RESULTS: In patients
      with elevated TnT level the incidence of the primary end point was 13.1% in the
      abciximab group Vs. 18.3% in the placebo group [relative risk (RR): 0.70; 95%
      confidence interval (CI), 0.52-0.95, P = 0.02]. The combined incidence of death
      or myocardial infarction was 12.9% in the abciximab group vs. 17.9% in the
      placebo group (RR: 0.71; 95% CI, 0.52-0.96, P = 0.03). In contrast, the incidence
      of the primary end point in patients with no elevated TnT level was identical in
      both treatment groups (4.6%). The risk of bleeding was not related to TnT level.
      CONCLUSIONS: Baseline troponin level affects the benefit of abciximab in patients
      with ACS undergoing PCI after pretreatment with a high loading dose of
      clopidogrel. Abciximab reduces the risk of ischemic events only in patients with
      ACS and elevated troponin level.

PMID- 18046528
TI  - Replacement of valved right ventricular to pulmonary artery conduits: an
      observational study with focus on right ventricular geometry.
AB  - OBJECTIVE: Timing of the operation for exchange of right ventricular (RV) to
      pulmonary artery (PA) conduits is a matter of considerable debate. We aimed to
      study the course of right ventricular dimension in patients undergoing conduit
      exchange. PATIENTS AND METHODS: We retrospectively studied all patients who
      underwent implantation and or replacement of RV/PA conduits during the time
      period between 1990 and 2005. Clinical and echocardiographic data were recorded
      as obtained at follow-up visits. RESULTS: A total of 229 (144 boys and 85 girls)
      underwent surgery for implantation and or replacement of RV/PA conduits during
      the study period. Patients were assigned to three age groups including 37
      infants, 125 children aged 1-10 years and 67 patients more than 10 years of age.
      185 pulmonary (81%) and 44 aortic homografts (19%) were implanted. Fifty-eight of
      these 185 patients (25%) required exchange of conduits after a median time of 6.4
      (8 months-12 years) (median (range)). The follow-up was 7.55 (0.1-17) years. The
      survival of the patients after homograft change was 98%. Freedom from failure for
      aortic and pulmonary homografts at an interval of 10 years for all patients was
      38.5% for aortic and 56.2% for pulmonary homografts (P = 0.018; Mann-Whitney).
      Age at conduit exchange (coefficient: -4.917; P < 0.001) and right ventricular
      end-diastolic dimension (RVDD) before conduit exchange (coefficient: 8.255; P <
      0.001) were related to RVDD as measured by M-mode echocardiography at follow-up
      ("best subset" regression analysis; R squared = 0.746). RVDD decreased in 48/58
      patients, remained unchanged in 8/58 and increased in 2/59 patients at follow-up.
      An increased RVDD was positively correlated to the duration of artificial
      ventilation after the operation for conduit exchange (R = 0.56; P < 0.001).
      CONCLUSIONS: Reoperation for exchange of degenerated conduits should be performed
      early to prevent the development of irreversible structural myocardial changes
      and persistence of right ventricular dilatation.

PMID- 18046529
TI  - Atrial tachycardias following circumferential pulmonary vein ablation:
      observations during catheter ablation.
AB  - Circumferential pulmonary vein ablation performing linear lesions around the
      ostia of the pulmonary veins has been shown to be effective for the treatment of
      atrial fibrillation. During the follow-up period, persistent atrial tachycardia
      may occur as a proarrhythmic complication. Only little information is available
      about the underlying mechanism. In our study, atrial tachycardia following
      circumferential pulmonary vein ablation was identified in 13 out of 84
      consecutive patients (15.5%), as a transient appearance in four and with
      recurrences for more than 3 months in nine patients (10.7%). Electrophysiological
      study and ablation was performed in eight cases, revealing common atrial flutter
      in two, a focal origin secondary to conduction recovery from the pulmonary vein
      to the left atrium in two and macro reentrant left atrial flutter in four
      patients. The electrophysiological characteristics demonstrated by
      electroanatomic activation mapping CARTO and consecutive ablation therapy with a
      100% success rate are described and discussed with regard to the literature.

PMID- 18046531
TI  - Skeletal muscle myofibrillar protein oxidation and exercise capacity in heart
      failure.
AB  - BACKGROUND: Heart failure is characterized by limited exercise tolerance and by a
      skeletal muscle myopathy with atrophy and shift toward fast fibres. An
      inflammatory status with elevated pro-inflammatory cytokines and exaggerated free
      radicals production can worsen muscle damage. We have previously demonstrated in
      a model of heart failure, the monocrotaline treated rat, that oxidation of
      skeletal muscle actin, tropomyosin and myosin produces a reduction of contractile
      efficiency, which may further depress muscle function and exercise capacity.
      AIMS: To investigate the presence of oxidized myofibrillar proteins in skeletal
      muscle of CHF patients by means of the Oxyblot technique and to correlate it with
      exercise capacity. METHODS: We have analyzed skeletal muscle biopsies taken from
      six patients with class III-IV NYHA CHF and four control patients (peak VO(2)
      12.8 +/- 1.9 vs. 29.7 +/- 1.7 ml/kg/min, p < 0.0001). RESULTS AND CONCLUSIONS: A
      correlation between degree of myofibrillar oxidation and exercise capacity
      measured as peak VO(2) was obtained. In the skeletal muscle of CHF patient there
      was a much higher level of myofibrillar protein oxidation as expressed by the
      Oxyblot/Red Ponceau (Oxy/RP) ratio as compared to controls (2.1 +/- 0.3 vs. 1.02
      +/- 0.09, p < 0.0001). The VO(2)/Oxy/RP was significantly lower in the CHF
      patients. Higher levels of muscle oxidation were found in patients with lower
      exercise capacity with an inverse correlation between Oxyblot and VO(2) values (r
      (2) = 0.83).

PMID- 18046530
TI  - Catheter-ablation of ventricular tachycardia in patients with coronary artery
      disease: influence of the endocardial substrate size on clinical outcome.
AB  - Ablation of symptomatic ventricular tachycardia (VT) in patients with coronary
      artery disease is frequently performed using the three dimensional mapping system
      CARTO. In the amplitude map, bipolar potentials of <1.5 mV are considered
      abnormal and represent damaged myocardium due to previous infarction. This
      pathological electrical area can be arrhythmogenic, serving as the substrate for
      reentrant VT. The purpose of this study was to correlate the size of the
      endocardial substrate with the success of VT catheter ablation. Included in this
      retrospective analysis were 69 consecutive patients with coronary artery disease
      who underwent ablation for symptomatic clinical VT using CARTO. The voltage maps
      were analyzed and the area with abnormal bipolar electrograms (<1.5 mV) was
      determined using geometric approximation models. The area of abnormal
      electrograms was divided into three sizes: small (<or=15 cm(2); 11 patients),
      medium (16-99 cm(2); 50 patients), and large (>or=100 cm(2); 8 patients). Patient
      characteristics were not different between the three substrate groups in regard
      to age, tachycardia cycle length, or number of radiofrequency applications,
      however differed significantly between the small, medium and large group in
      regard to left ventricular ejection fraction (44 +/- 12% vs. 32 +/- 9% vs. 21 +/-
      7%, respectively; P = 0.001). Overall, there was a significant correlation
      between myocardial infarction locations and endocardial substrate sizes (P =
      0.031), such that 73% of small substrates were found after inferior myocardial
      infarctions, and 100% of large substrates after anterior and multiple myocardial
      infarctions (P = 0.003). After ablation, inducibility of ventricular arrhythmias
      was more rare in patients with small substrates compared to patients with medium
      or large substrates (small substrates: 9%, medium and large substrates: 43%, P =
      0.043). Although during follow-up of 25 +/- 17 months (1 day to 72 months) there
      was no significant difference between endocardial substrate sizes in regard to
      recurrence rates (small: 27%, medium: 38%, large: 50%, P = 0.588), patients with
      a small substrate did not have fast VT or ventricular fibrillation (VF), in
      contrast to 30% and 38% of patients with medium and large substrates,
      respectively. We conclude that in patients with coronary artery disease a small
      area of low amplitude bipolar potentials (<or=15 cm(2)) was seen more often after
      inferior myocardial infarction than after anterior and multiple infarctions.
      After ablation, patients with small substrates were rarely inducible and showed a
      more benign course during follow-up (trend towards fewer arrhythmia recurrences
      and no fast VT or VF). As a result smaller arrhythmogenic substrates appear to be
      better amenable to catheter ablation than larger substrates.

PMID- 18046532
TI  - Analysis of TaALMT1 traces the transmission of aluminum resistance in cultivated
      common wheat (Triticum aestivum L.).
AB  - Allele diversities of four markers specific to intron three, exon four and
      promoter regions of the aluminum (Al) resistance gene of wheat (Triticum aestivum
      L.) TaALMT1 were compared in 179 common wheat cultivars used in international
      wheat breeding programs. In wheat cultivars released during the last 93 years,
      six different promoter types were identified on the basis of allele size. A
      previous study showed that Al resistance was not associated with a particular
      coding allele for TaALMT1 but was correlated with blocks of repeated sequence
      upstream of the coding sequence. We verified the linkage between these promoter
      alleles and Al resistance in three doubled haploid and one intercross populations
      segregating for Al resistance. Molecular and pedigree analysis suggest that Al
      resistance in modern wheat germplasm is derived from several independent sources.
      Analysis of a population of 278 landraces and subspecies of wheat showed that
      most of the promoter alleles associated with Al resistance pre-existed in Europe,
      the Middle East and Asia prior to dispersal of cultivated germplasm around the
      world. Furthermore, several new promoter alleles were identified among the
      landraces surveyed. The TaALMT1 promoter alleles found within the spelt wheats
      were consistent with the hypothesis that these spelts arose on several
      independent occasions from hybridisations between non-free-threshing tetraploid
      wheats and Al-resistant hexaploid bread wheats. The strong correlation between Al
      resistance and Al-stimulated malate efflux from the root apices of 49 diverse
      wheat genotypes examined was consistent with the previous finding that Al
      resistance in wheat is conditioned primarily by malate efflux. These results
      demonstrate that the markers based on intron, exon and promoter regions of
      TaALMT1 can trace the inheritance of the Al resistance locus within wheat
      pedigrees and track Al resistance in breeding programmes.

PMID- 18046533
TI  - Sexual function in ICU survivors more than 3 years after major trauma.
AB  - OBJECTIVE: To study sexual function in trauma patients 3-8 years after discharge
      from an ICU and to assess determinants of poor sex life. DESIGN AND SETTING: A
      postal questionnaire survey was conducted in 2006 on a cohort of 325 consecutive
      adult ICU trauma patients admitted to a university hospital during 1998-2003.
      PATIENTS: Of 210 eligible patients 156 (74%) answered the questionnaires. Mean
      age was 46 years, and 124 were males. MEASUREMENTS AND RESULTS: Sexual function
      was assessed by a self-report measure, and patients were asked to describe sexual
      life both currently and prior to trauma. The International Index of Erectile
      Function evaluated erectile function in males. At follow-up 50% reported sexual
      function to be unchanged, 41% impaired, and 9% to be better than preinjury
      status; 34% reported that the trauma impaired current sex life. Erectile
      dysfunction was found in 27% of men younger than 40 years and 51% of men 40 years
      or older. Age, being single, Injury Severity Score, and depression were
      associated with poor sexual function. Of 17 patients experiencing breakdown of a
      regular relationship 71% reported the trauma to be a significant contributor.
      CONCLUSIONS: At follow-up more than 3 years after injury one-third of our ICU
      trauma patients reported that the trauma impaired sexual function. Erectile
      dysfunction was significantly more frequent among men younger than 40 years than
      found in studies of the normal population. Evaluation of sexual function should
      be part of long-term outcome assessment after major trauma.

PMID- 18046534
TI  - Pharmacokinetics of high-dose nebulized amikacin in mechanically ventilated
      healthy subjects.
AB  - OBJECTIVE: Nebulized amikacin may be an attractive option for the treatment of
      lung infections. Low systemic absorption may permit the use of high doses,
      leading to high lung concentrations without systemic toxicity. We evaluated the
      pharmacokinetics and safety of an optimized high-dose amikacin nebulization
      technique. DESIGN: in vitro and in vivo pharmacokinetic study. PATIENTS AND
      PARTICIPANTS: Six healthy volunteers (age 21-30 years, weight 49-68 kg).
      INTERVENTIONS: The Aeroneb Pro nebulizer with an Idehaler vertical spacer was
      evaluated in a bench study. Amikacin was administered intravenously (15[Symbol:
      see text]mg/kg) and nebulized (40, 50, and 60[Symbol: see text]mg/kg) during
      noninvasive pressure-support ventilation through a mouthpiece. MEASUREMENTS AND
      RESULTS: Median (interquartile range) in vitro inhaled fraction was 31% (30-32)
      and inhalable output was 681 mg/h (630-743). Serum concentrations after
      nebulization were less than or equal to those after infusion. The area under the
      serum concentration curve was significantly higher after infusion (138 mg h(-1)l(
      1), 122-143) than after nebulization (49 mg h(-1)l(-1), 39-55, at 40 mg/kg; 63,
      53-67 at 50; 66, 50-71, at 60). Peak serum concentration was also higher after
      infusion: 48 mg/l (45-49) after infusion compared to 8.2 (5.6-8.7), 9.2 (7.6
      10.2), and 9.2 (5.2-10.3), respectively. Mean absorption times after nebulization
      were 2 h 24 min (2,07-2,45), 2 h 21 min (2,07-2,35), and 2 h 5 min (2,00-2,25),
      respectively. No side effect was observed. CONCLUSIONS: Nebulization of up to 60
      mg/kg amikacin appears to be safe in healthy subjects and associated with lower
      serum concentrations than a 15 mg/kg infusion.

PMID- 18046535
TI  - Magnetic resonance imaging changes in the pituitary gland following acute
      traumatic brain injury.
AB  - OBJECTIVE: The objective was to study the anatomical changes in the pituitary
      gland following acute moderate or severe traumatic brain injury (TBI). DESIGN:
      Retrospective, observational, case-control study. SETTING: Neurosciences Critical
      Care Unit of a university hospital. PATIENTS: Forty-one patients with moderate or
      severe TBI who underwent magnetic resonance imaging (MRI) during the acute phase
      (less than seven days) of TBI. MRI scans of 43 normal healthy volunteers were
      used as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient
      demographics, Acute Physiology and Chronic Health Evaluation II (APACHE II)
      score, Injury Severity Score (ISS), post-resuscitation Glasgow Coma Score (GCS),
      Glasgow Outcome Score (GOS), mean intracranial pressure (ICP), mean cerebral
      perfusion pressure (CPP), computed tomography (CT) data, pituitary gland volumes
      and structural lesions in the pituitary on MRI scans. The pituitary glands were
      significantly enlarged in the TBI group (the median and interquartile range were
      as follows: cases 672 mm3 (range 601-783 mm3) and controls 552 mm3 (range 445-620
      mm3); p value<0.0001). APACHE II, GCS, GOS and ICP were not significantly
      correlated with the pituitary volume. Twelve of the 41 cases (30%) demonstrated
      focal changes in the pituitary gland (haemorrhage/haemorrhagic infarction (n=5),
      swollen gland with bulging superior margin (n=5), heterogeneous signal
      intensities in the anterior lobe (n=2) and partial transection of the
      infundibular stalk (n=1). CONCLUSIONS: Acute TBI is associated with pituitary
      gland enlargement with specific lesions, which are seen in approximately 30% of
      patients. MRI of the pituitary may provide useful information about the
      mechanisms involved in post-traumatic hypopituitarism.

PMID- 18046536
TI  - Does harvesting the hamstrings for ACL reconstruction impair the muscular
      function of the knee joint?

PMID- 18046537
TI  - Reliability of bony landmarks for restoration of the joint line in revision knee
      arthroplasty.
AB  - The aim of this study was to determine the reliability of bone landmarks for
      restoring the joint line in revision knee arthroplasty. The relationship of the
      femoral epicondyles, the tibial tubercle (TT) and the fibular head (FH) to the
      joint line was measured on 200 magnetic resonance imaging (MRI, 100 females, 100
      males), including assessment on intraobserver and interobserver reliability. MRI
      scans demonstrating chondral lesions and osteoarthritis were excluded, as were
      patients with immature skeletons or a history of previous knee surgery. Sequences
      in sagittal, coronal and axial planes were used as well as cross-referencing with
      the same computer software. In order to account for size differences between
      patients, each bony landmark measurement was converted to a ratio relative to the
      femoral or/and tibial width. We found a transepicondylar axis equal to 3.11
      degrees (+/-1.9). The average distance from the epicondyles to the joint line was
      respectively 23 mm on the lateral side and 28 mm on the medial side. However
      there was a variation of distance from the epicondyles of the joint line up to 11
      mm and a significative difference was found between male and female. We
      determined the distances from the tip of the FH and from the TT to the joint
      line. The joint line-FH distance averaged 14 mm (range 4.1-22.13) with no gender
      difference. The joint line-TT distance was averaged 22 mm (range 10.61-32.09). We
      determined an epicondylar ratio (distance from the lateral epicondyle to the
      joint line related to the femoral width). We found this ratio averaged 28% with
      no gender difference (P = 0.09). There is a large variation of bony landmarks
      depending on the size of the individual. Considering this findings, the FH is not
      a reliable guide for the joint line in revision surgery. Previous studies have
      measured the absolute values from various landmarks to the joint line. This study
      provides a significant advantage, in that the level of the joint line can be
      determined for each individual by using a ratio to account for gender and size
      differences.

PMID- 18046538
TI  - In vivo effects of chronic contamination with 137 cesium on testicular and
      adrenal steroidogenesis.
AB  - More than 20 years after Chernobyl nuclear power plant explosion, radionuclides
      are still mainly bound to the organic soil layers. The radiation exposure is
      dominated by the external exposure to gamma-radiation following the decay of
      (137)Cs and by soil-to-plant-to-human transfer of (137)Cs into the food chain.
      Because of this persistence of contamination with (137)Cs, questions regarding
      public health for people living in contaminated areas were raised. We
      investigated the biological effects of chronic exposure to (137)Cs on testicular
      and adrenal steroidogenesis metabolisms in rat. Animals were exposed to
      radionuclide in their drinking water for 9 months at a dose of 6,500 Bq/l (610
      Bq/kg/day). Cesium contamination decreases the level of circulating 17beta
      estradiol, and increases corticosterone level. In testis, several nuclear
      receptors messenger expression is disrupted; levels of mRNA encoding Liver X
      receptor alpha (LXRalpha) and LXRbeta are increased, whereas farnesoid X receptor
      mRNA presents a lower level. Adrenal metabolism presents a paradoxical decrease
      in cyp11a1 gene expression. In conclusion, our results show for the first time
      molecular and hormonal modifications in testicular and adrenal steroidogenic
      metabolism, induced by chronic contamination with low doses of (137)Cs.

PMID- 18046539
TI  - Effects of in utero meso-2,3-dimercaptosuccinic acid with calcium and ascorbic
      acid on lead-induced fetal development.
AB  - To examine the effects of meso-2,3-dimercaptosuccinic acid (DMSA) on
      developmental toxicity resulting from exposure to lead in utero, female albino
      mice were exposed to lead by drinking water contaminated with lead acetate for 4
      weeks. After the cessation of lead exposure, female mice were supplemented by
      gavage with saline solution, DMSA, or DMSA and calcium as well as ascorbic acid
      from the fourth day of gestation until parturition, respectively. Lead levels
      (blood, liver, and bone) were measured at birth. Pups were then tested about
      neural development including surface righting reflex, cliff avoidance and air
      righting reflex. The markers of physical maturation, such as body weight, pinna
      unfolding, incisor eruption, and eye opening were also recorded. DMSA treatment
      decreased blood lead levels of pregnant mice, however, increased lead levels in
      both liver and bone of fetus, and delayed the early physical and neural
      development of offspring. Calcium and ascorbic acid reduced the transfer of lead
      to fetus. In conclusion, DMSA treatment during pregnancy enhances lead-induced
      fetal developmental toxicity.

PMID- 18046540
TI  - Inhibition of poly(ADP-ribose) polymerase (PARP) influences the mode of sulfur
      mustard (SM)-induced cell death in HaCaT cells.
AB  - Sulfur mustard (SM) is a bifunctional alkylating agent. Its primary toxic
      consequence is severe skin damage with blisters, occurring after skin contact.
      These vesicant properties of SM have been linked to cell death of proliferating
      keratinocytes in the basal layer of the skin. Catalytic activation of the nuclear
      enzyme poly(ADP-ribose) polymerase (PARP-1) has been demonstrated to be a major
      event in response to high levels of DNA damage, and PARP-1 activation may be part
      of apoptotic signaling. In other contexts, overstimulation of PARP-1 triggers
      necrotic cell death because of rapid consumption of its substrate, beta
      nicotinamide adenine dinucleotide (NAD+) and the consequent depletion of ATP.
      These findings prompted us to evaluate whether SM induces apoptosis in
      keratinocytes like HaCaT cells and to determine whether blocking of PARP enzyme
      activity with 3-aminobenzamide (3AB) can influence the mode of cell death. HaCaT
      cells were exposed to SM (10-1,000 microM; 30 min) and then cultivated in SM-free
      medium with or without 3AB for up to 48 h. This treatment resulted in a time and
      SM dose-dependent increase of apoptotic cell death characterized by PARP-1
      cleavage and DNA fragmentation during the experimental period. After just 45 min
      of exposure to 1 mM SM, we observed a significant increase in PARP-1 activity in
      HaCaT cells. About 6 h after exposure, intracellular ATP levels were diminished
      by 22%, which seemed to be completely prevented by the addition of 3AB directly
      after exposure. However, 18 h later, this 3AB effect on the SM concentration
      dependent loss of ATP was no longer detectable. Interestingly, the effect of SM
      on total cell viability was not changed by 3AB. However, the mode of cell death
      was influenced by 3AB exhibiting an increase of apoptotic cells and a concomitant
      decrease of necrotic HaCaT cells during the first 24 h after SM exposure. Our
      results indicate that SM concentrations of 1 mM or higher induce a prominent PARP
      activation leading to ATP depletion and necrosis. In contrast, lower
      concentrations of SM cause minor PARP activation and, especially, PARP-1 cleavage
      by caspase 3 without ATP depletion. Because ATP is required for apoptosis, we
      suggest that ATP acts as an early molecular switch from apoptotic to necrotic
      modes of SM-induced cell death, at least at high concentrations (> or =1 mM).
      Thus, the observed early proapoptotic effect of 3AB at lower SM concentrations
      may point to the influence of ATP-independent cell-death regulating mechanisms.

PMID- 18046541
TI  - Sorbitol-induced apoptosis of human leukemia is mediated by caspase activation
      and cytochrome c release.
AB  - It has been reported that sorbitol induces apoptosis in several cancer cell
      lines. However, the molecular mechanism underlying the sorbitol-induced apoptotic
      process is not yet clearly understood. In the present study, the intracellular
      signaling pathways of sorbitol-induced apoptosis in human K562 cells were
      investigated using both morphological analysis and DNA fragmentation technique.
      In this study, we demonstrated that sorbitol-induced apoptosis in human K562
      cells is a concentration- and time-dependent manner. This sorbitol-induced
      apoptosis in human K562 cells was also accompanied by the up-regulation of Bax,
      and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L).
      Moreover, the sorbitol treatment resulted in a significant reduction of
      mitochondria membrane potential, increase in the release of mitochondrial
      cytochrome c (cyt c), and activation of caspase 3. Furthermore, treatment with
      caspase 3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced
      caspase 3 activity and cell death. These results clearly demonstrate that the
      induction of apoptosis by sorbitol involves multiple cellular/molecular pathways
      and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins,
      mitochondrial membrane potential, mitochondrial cyt c, and caspase 3, they all
      participate in sorbitol-induced apoptotic process in human K562 cells.

PMID- 18046542
TI  - A novel mechanism of mechanical stress-induced angiotensin II type 1-receptor
      activation without the involvement of angiotensin II.
AB  - The angiotensin II (AngII) type 1 (AT1) receptor is a seven transmembrane
      spanning G-protein-coupled receptor, and the activation of AT1 receptor plays an
      important role in the development of load-induced cardiac hypertrophy. Locally
      generated AngII was believed to trigger cardiac hypertrophy by an autocrine or
      paracrine mechanism. However, we found that mechanical stress can activate AT1
      receptor independently of AngII. Without the involvement of AngII, mechanical
      stress not only activates extracellular signal-regulated kinases in vitro, but
      also induces cardiac hypertrophy in vivo. All of these events are inhibited by
      candesartan as an inverse agonist for AT1 receptor. It is conceptually novel that
      AT1 receptor directly mediates mechanical stress-induced cellular responses, and
      inverse-agonist activity emerges as an important pharmacological parameter for
      AT1-receptor blockers that determines their efficacy in preventing organ damage
      in cardiovascular diseases.

PMID- 18046543
TI  - Sphingosine-1-phosphate and endothelin-1 induce the expression of rgs16 protein
      in cardiac myocytes by transcriptional activation of the rgs16 gene.
AB  - The expression of the negative Regulator of G protein signaling 16 (RGS16) is
      rapidly induced in cardiomyocytes by various stimuli. To identify the promoter of
      the mouse RGS16 gene, a 1.8-kb deoxyribonucleic acid fragment 5' of the RGS16
      coding region was subcloned into a firefly-luciferase reporter vector and four
      overlapping fragments were analyzed. The luciferase production was quantified in
      neonatal rat cardiac myocytes (NRCM). A 0.6-kb fragment that induced a tenfold
      increase in luciferase activity contained the minimal promoter sequence. Its
      activity was twofold stimulated by fetal calf serum, endothelin-1 (ET-1), and
      sphingosine 1-phosphate (S1P), which stimuli also elevated the level of RGS16
      protein. Stimulation of NRCM with ET-1 induced activation of the monomeric
      GTPases RhoA and Rac1, whereas S1P and the selective S1P1 receptor agonist
      SEW2871 only induced a pronounced activation of Rac1. In accordance, the
      treatment with the Rho-, Rac-, and Cdc42-inactivating Clostridium difficile Toxin
      B (TcdB) 10463 inhibited ET-1 and S1P-induced transcriptional activation. The ET
      1-induced activation was insensitive to pertussis toxin but selectively
      suppressed by the RhoA-C-specific C2I-C3 ADP-ribosyl transferase and the ET(B)
      receptor antagonist BQ788. The S1P-induced activation was specifically inhibited
      by pertussis toxin and the Rac-inactivating TcdB 1470. All stimulated
      transcriptional activity was abolished by the negative transcription factor Yin
      Yang 1 (YY1), which binds to a consensus sequence within the minimal promoter.
      Taken together, our data show that most likely ET(B)- and S1P1-receptors induce
      RGS16 protein expression in cardiac myocytes by increasing the transcriptional
      activity of the rgs16 gene. This activation is mediated by heterotrimeric G
      proteins, Rho GTPases, and is under negative control of the transcription factor
      YY1.

PMID- 18046545
TI  - A sigmoid function is the best fit for the ascending limb of the Hoffmann reflex
      recruitment curve.
AB  - The Hoffmann (H)-reflex has been studied extensively as a measure of spinal
      excitability. Often, researchers compare the H-reflex between experimental
      conditions with values determined from a recruitment curve (RC). An RC is
      obtained experimentally by varying the stimulus intensity to a nerve and
      recording the peak-to-peak amplitudes of the evoked H-reflex and direct motor (M)
      wave. The values taken from an RC may provide different information with respect
      to a change in reflex excitability. Therefore, it is important to obtain a number
      of RC parameters for comparison. RCs can be obtained with a measure of current
      (HCRC) or without current (HMRC). The ascending limb of the RC is then fit with a
      mathematical analysis technique in order to determine parameters of interest such
      as the threshold of activation and the slope of the function. The purpose of this
      study was to determine an unbiased estimate of the specific parameters of
      interest in an RC through mathematical analysis. We hypothesized that a
      standardized analysis technique could be used to ascertain important points on an
      RC, regardless of data presentation methodology (HCRC or HMRC). For both HCRC and
      HMRC produced using 40 randomly delivered stimuli, six different methods of
      mathematical analysis [linear regression, polynomial, smoothing spline, general
      least squares model with custom logistic (sigmoid) equation, power, and
      logarithmic] were compared using goodness of fit statistics (r-square, RMSE).
      Behaviour and robustness of selected curve fits were examined in various
      applications including RCs generated during movement and somatosensory
      conditioning from published data. Results show that a sigmoid function is the
      most reliable estimate of the ascending limb of an H-reflex recruitment curve for
      both HCRC and HMRC. Further, the parameters of interest change differentially
      with respect to the presentation methodology and the analysis technique. In
      conclusion, the sigmoid function is a reliable analysis technique which mimics
      the physiologically based prediction of the input/output relation of the
      ascending limb of the recruitment curve. Therefore, the sigmoid function should
      be considered an acceptable and preferable analytical tool for H-reflex
      recruitment curves obtained with reference to stimulation current or M-wave
      amplitude.

PMID- 18046544
TI  - Noradrenergic neuromodulation of human attention for emotional and neutral
      stimuli.
AB  - INTRODUCTION: Norepinephrine (NE) has a regulatory role in human attention.
      OBJECTIVE: To examine its role in emotional modulation of attention, we used an
      attentional blink (AB) paradigm, in the context of psychopharmacological
      manipulation, where targets were either emotional or neutral items. RESULTS AND
      DISCUSSION: We report behavioural evidence that beta-adrenergic blockade with
      propranolol impairs attention independent of target valence. Furthermore, this
      effect is centrally mediated as administration of the peripheral beta-adrenergic
      antagonist nadolol did not impair attention. By contrast, increasing NE tone,
      using the selective NE reuptake inhibitor reboxetine, improves detection of
      emotional stimuli. CONCLUSION: In line with theoretical and animal models, these
      findings provide human behavioural evidence that the adrenergic system has a
      modulatory influence on selective attention that in some instances depends on
      item valence.

PMID- 18046546
TI  - Neuroapplication of Amplatzer vascular plug: a novel device for parent artery
      occlusion.
AB  - Extracranial internal carotid aneurysms are rare, but the complications
      associated with the traditional surgical reconstruction methods are relatively
      high. Endovascular treatment has replaced surgery for treatment of a variety of
      vascular problems. We describe here the treatment of a recurrent extracranial
      internal carotid artery aneurysm using a detachable balloon combined with the
      Amplatzer vascular plug.

PMID- 18046547
TI  - Pediatric musculoskeletal MRI: basic principles to optimize success.
AB  - The purpose of this general review is to suggest practical strategies to optimize
      musculoskeletal MR imaging in children. The changes related to ossification and
      marrow transformation affect the MRI appearance during development. This review
      summarizes the normal appearance of the growing skeleton on various pulse
      sequences, as well as ways to optimize the imaging parameters. Appropriate
      patient positioning, choice of field of view and imaging coils are essential.
      There are various tools including intravenous contrast agent administration, fat
      suppression and parallel imaging that can enhance the depiction of abnormalities,
      increase speed of imaging, and improve overall quality of the study. Finally,
      special considerations for imaging at 3 T are also reviewed.

PMID- 18046548
TI  - CLEC2A: a novel, alternatively spliced and skin-associated member of the NKC
      encoded AICL-CD69-LLT1 family.
AB  - The human natural killer gene complex (NKC) encodes for numerous C-type lectin
      like receptors (CTLR), which are expressed on various immune cells including
      natural killer (NK) cells and myeloid cells. Certain activation-induced, NKC
      encoded CTLR are grouped into the C-type lectin domain family 2 (CLEC2 family)
      which, in humans, comprises AICL (CLEC2B), CD69 (CLEC2C), and LLT1 (CLEC2D). In
      this paper, we characterize a novel member of the CLEC2 family, the human orphan
      gene CLEC2A. The C-type lectin-like domain (CTLD) of CLEC2A is most similar to
      the CTLD of LLT1 ( approximately 60% similarity). Like mouse CLEC2 family members
      Clr-b and Clr-g, CLEC2A lacks two highly conserved cysteines (Cys4 and Cys5),
      which form an intramolecular bond in the CTLD of most CTLR. Alternative splicing
      of exon 2 and of two distinct terminal exons (exon 5A/B), respectively, gives
      rise to four CLEC2A variants differing in the usage of the transmembrane domain
      and/or in the carboxyterminal portion of the CTLD. CLEC2A transcripts were
      detected primarily in myeloid cell lines, but not in epithelial cell lines. In
      tissues, CLEC2A is selectively expressed in the skin and, at lower abundance, in
      hematopoietic and gonadal tissues. Finally, we show that the CLEC2A1 variant is
      readily expressed at the cell surface, where it may serve as a ligand for NKC
      encoded NK receptors.

PMID- 18046549
TI  - WHO-IUIS Nomenclature Subcommittee for immunoglobulins and T cell receptors
      report.

PMID- 18046550
TI  - Generation of readily transformable Bacillus licheniformis mutants.
AB  - A set of mutants was generated by targeted deletion of the hsdR loci of two type
      I restriction modification systems (RMS) identified in Bacillus licheniformis
      DSM13. Single as well as double knock-outs resulted in strains being readily
      transformable with plasmids isolated from Bacilli. Introduction of shuttle
      plasmids isolated from Escherichia coli was routinely possible when the double
      mutant B. licheniformis MW3 (DeltahsdR1, DeltahsdR2) was used in transformation
      experiments. Growth and secretion of extracellular enzymes were not affected in
      any of the mutants. Thus, along with an optimized transformation protocol, this
      study makes available an urgently needed transformation system for this
      industrially exploited species.

PMID- 18046551
TI  - Complete hydrolysis of myo-inositol hexakisphosphate by a novel phytase from
      Debaryomyces castellii CBS 2923.
AB  - Debaryomyces castellii phytase was purified to homogeneity in a single step by
      hydrophobic interaction chromatography. Its molecular mass is 74 kDa with 28.8%
      glycosylation. Its activity was optimal at 60 degrees C and pH 4.0. The K (m)
      value for sodium phytate was 0.532 mM. The enzyme exhibited a low specificity and
      hydrolyzed many phosphate esters. The phytase fully hydrolyzed myo-inositol
      hexakisphosphate (or phytic acid, Ins P(6)) to inositol and inorganic phosphate.
      The sequence of Ins P(6) hydrolysis was determined by combining results from high
      performance ionic chromatography and nuclear magnetic resonance. D. castellii
      phytase is a 3-phytase that sequentially releases phosphate groups through Ins
      (1,2,4,5,6) P(5), Ins (1,2,5,6) P(4), Ins (1,2,6) P(3), Ins (1,2) P(2), Ins (1 or
      2) P(1), and inositol (notation 3/4/5/6/1 or 2).

PMID- 18046552
TI  - Intra-tendinous ganglion in the long head of the biceps humeri.
AB  - We present details of a case of intra-tendinous ganglion arising from the long
      head of the biceps at an unusual location. MRI scans have important implications
      for surgical planning and treatment. After excision of the ganglion, the tendon
      remaining could be repaired. Five months after surgery, there was no sign of
      recurrence.

PMID- 18046553
TI  - Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I
      antigen presentation by melanoma cells.
AB  - Histone deacetylase inhibitors (HDACi), including trichostatin A (TSA) and
      valproic acid, can alter the acetylation of histones in chromatin and enhance
      gene transcription. Previously we demonstrated that HDACi-treated tumor cells are
      capable of presenting antigen via the MHC class II pathway. In this study, we
      show that treatment with HDACi enhances the expression of molecules (TAP1, TAP2,
      LMP2, LMP7, Tapasin and MHC class I) involved in antigen processing and
      presentation via the MHC class I pathway in melanoma cells. HDACi treatment of
      B16F10 cells also enhanced cell surface expression of class I and costimulatory
      molecules CD40 and CD86. Enhanced transcription of these genes is associated with
      a significant increase in direct presentation of whole protein antigen and MHC
      class I-restricted peptides by TSA-treated B16F10 cells. Our data indicate that
      epigenetic modification can convert a tumor cell to an antigen presenting cell
      capable of activating IFN-gamma secreting T cells via the class I pathway. These
      findings suggest that the abnormalities, observed in some tumors in the
      expression of MHC class I antigen processing and presentation molecules, may
      result from epigenetic repression.

PMID- 18046554
TI  - Patient demographics and disease variables correlate with distinct cytokine
      patterns in mitogen-stimulated peripheral blood mononuclear cells from rheumatoid
      arthritis patients.
AB  - There is paucity of literature on the association of peripheral blood cytokine
      patterns with patient demographics and disease variables in rheumatoid arthritis
      (RA). We test the hypothesis that there may be differences in peripheral blood
      levels of inflammatory cytokines in RA subjects according to various disease
      variables. In this case, we could identify peripheral blood cytokine markers that
      correlate with different disease variables. Forty-two seropositive RA patients
      were characterized according to the age at onset, gender, disease duration,
      severity, activity and ACR functional class. The production levels in mitogen
      stimulated PBMCs of five pro-inflammatory cytokines (IFNgamma, TNFalpha, TNFbeta,
      IL-8, IL-18) and three anti-inflammatory cytokines (IL-4, IL-10, IL-13) were
      evaluated in these patients and in healthy controls. Several new findings emerge:
      (1) higher levels of IL-4 correlate with female gender, milder disease, non
      erosive disease, and earlier age at onset; (2) higher levels of IL-10 correlate
      with the requirement of < or =2 DMARDs; (3) higher levels of IL-18 correlate with
      non-erosive disease and younger age at onset; (4) higher TNFbeta levels correlate
      with older present age of patients; and (5) higher IL-8 levels correlate with
      established/late disease. There are several interesting differences in cytokine
      patterns with respect to age at onset, current age, disease severity, and the
      number of DMARDs the patients require.

PMID- 18046555
TI  - [Secondary toric intraocular lens implantation in pseudophakic eyes. The add-on
      IOL system].
AB  - The last 2 years have seen the development of toric IOL especially designed for
      implantation in the ciliary sulcus for correction of corneal astigmatism in
      pseudophakic eyes. The term 'add-on IOL systems' is becoming more and more widely
      accepted for the lenses used in this procedure. The main indications for it are
      regular corneal astigmatism in pseudophakic eyes, for example following
      perforating keratoplasty, or when corneal scarring is present following trauma or
      infection. The implantation is a simple atraumatic procedure carried out under
      topical anaesthesia through a sclerocorneal incision. When the IOL is oriented
      along the steepest corneal meridian with the aid of corneal topographical
      monitoring, reliable and lasting correction of even extremely pronounced
      astigmatism is possible. Although this procedure has proved to be very efficient
      over a long follow-up period in small patient populations, reports of later
      adjustment of the rotation of toric add-on IOLs must be tested in further trials,
      especially in the case of simultaneous implantation of endocapsular IOLs in both
      eyes. Nonetheless, the possibility of later correction and reversibility of the
      intervention are further advantages of this lens system. As well as the
      correction of astigmatism in pseudophakic eyes the add-on IOL system also offers
      the option of treating pseudophakic eyes with sulcus-fixed multifocal lenses in
      the context of refractive interventions, e.g. as a secondary procedure.

PMID- 18046556
TI  - [Toric IOLs after cataract surgery and refractive lens exchange].
AB  - Patients with astigmatism (e.g. regular or keratoplasty-induced astigmatism) who
      undergo cataract surgery or refractive lens exchange with a standard monofocal
      IOL are often disappointed. Toric IOLs (T-IOLs) are, therefore, an excellent
      alternative for this condition. T-IOLs are now available from companies such as
      Alcon, Acri, Tec, Humanoptics, Wavelight, Rayner and Staar. Apart from Alcon and
      Staar who only produce T-IOLs with a fixed torus, all these produce customised
      lenses. The calculations needed for production of the T-IOLs are generally done
      by the companies and are based on the corneal astigmatism. T-IOLs have shown good
      rotational stability and good functional results. Corneal astigmatism can still
      be measured postoperatively, as it is corrected inside the eye. The referring
      ophthalmologist should exercise discretion when prescribing spectacles after
      surgery of this kind.

PMID- 18046557
TI  - [Toric phakic intraocular lenses].
AB  - After more than 3 years of follow-up, the satisfactory results achieved with the
      toric iris-fixated phakic intraocular lens (IOL) mean we can regard implantation
      of this lens as a procedure with the potential to provide safe, predictable,
      effective and stable correction of astigmatic errors, providing patients are
      carefully selected and receive adequate preparation for surgery. The iris-fixated
      toric phakic IOL (Verisyse, Advanced Medical Optics; Artisan, Ophtec) is a PMMA
      lens with a total diameter of 8.5 mm and an optic diameter of 5 mm. It has a
      spherical anterior and a toric posterior surface. Its refractive power ranges
      from -2 dpt to -21 dpt for myopia and from +2 dpt to +12.5 dpt for the correction
      of hyperopia. Cylindrical correction is available from 2 dpt to 7.5 dpt. The
      Visian toric implantable Collamer lens (Staar) differs in that it is foldable and
      can be inserted through a very small incision of about 2.8 mm. It is placed in
      front of the natural lens in the ciliary sulcus. The aim of implanting these
      phakic IOLs is to correct the entire refractive error, meaning both the spherical
      and the astigmatic error, in a single step. Different lens models are available,
      and the selection depends on the direction of the cylinder axis and the
      anatomical situation, among other things.

PMID- 18046558
TI  - Re: Unusual penetrating cranio-cerebral injuries in children from main plugs.

PMID- 18046559
TI  - Intracranial hemorrhages due to late-type vitamin K deficiency bleeding.
AB  - OBJECTS: Vitamin K deficiency bleeding (VKDB) represents a clinical picture
      characterized by bleedings due to insufficient levels of vitamin-K-dependent
      hemostatic factors. VKDB can be classified into three groups as early, classic,
      and late according to time of occurrence. Late-type VKDB has particular
      importance due to frequent intracranial hemorrhages that lead to high mortality
      and morbidity. In our study, we aimed to emphasize the importance of vitamin K
      prophylaxis in prevention of late-type VKDB. MATERIALS AND METHODS: Data of 12
      infants treated for intracranial hemorrhage due to late-type VKDB in Baskent
      University Hospitals between June 1998 and June 2005 have been analyzed. RESULTS:
      The ages of patients ranged between 25 and 90 days. Five were born in the
      hospital and seven were born at home. None of the infants born at home received
      vitamin K prophylaxis. Hemorrhages were classified as intraparenchymal in 58.33%,
      subarachnoid in 50.00%, subdural in 50.00%, intraventricular in 41.66%, and
      epidural in 8.33% according to cranial computerized tomography findings. Surgery
      was performed in seven cases (58.33%). A total of six patients died (50.00%).
      Three of the deaths were from the surgery-performed group. CONCLUSION: All
      newborns should receive vitamin K prophylaxis to prevent bleeding due to vitamin
      K deficiency. Symptoms of any predisposing disease and warning bleeds must be
      noticed early and additional doses of vitamin K should be administered, if
      required.

PMID- 18046560
TI  - Postoperative psychological status of children with anorectal malformations.
AB  - Our purpose was to clarify factors that influence the level of depression of
      Japanese children with anorectal malformations (ARM). The subjects comprised 66
      children with ARM, aged 0-16 years, and their mothers. Patients were divided into
      three groups (Group 1: aged 0-5 years, Group 2: 6-11 years, and Group 3: 12-16
      years). The level of depression of the children aged 6-16 years was investigated
      by Kovac's children's depression inventory (CDI). The psychological status of
      their mothers was assessed by Spielberger's state-trait anxiety index (STAI) and
      Zung's self-rating depression scale (SDS). The classification of ARM and the
      clinical condition were also investigated. Defecation scores were assigned for
      the degree of bowel dysfunction. The level of depression in the patients was more
      marked in Group 3 than in Group 2 according to the CDI score. Significant
      correlations between the CDI score of the child and the STAI-1, STAI-2 and SDS
      scores of the mother were observed in Group 2, but not in Group 3. In Group 2,
      the STAI-1 score of the mothers was significantly influenced by the degree of
      bowel dysfunction in her child. In Group 3, the CDI score was significantly
      correlated with the constipation score. This study revealed that bowel
      dysfunction is the important factor that influences the level of depression of
      the children with ARM. In the period of childhood during which the child attends
      primary school, bowel dysfunction indirectly influences the level of depression
      of children through the psychological status of mothers. However, bowel
      dysfunction directly influences the level of depression of children in adolescent
      patients.

PMID- 18046561
TI  - Predictive clinicopathologic factors for limited response of T3 rectal cancer to
      combined modality therapy.
AB  - PURPOSE: The response of T3 rectal cancer to combined modality therapy (CMT) is
      highly predictive of long-term outcome following surgery. The aim of this study
      was to identify pretreatment factors associated with poor tumor response to
      neoadjuvant chemoradiation. METHODS: A prospective institutional database at
      Memorial Sloan-Kettering Cancer Center was queried for endorectal ultrasound
      (ERUS) stage T3N0-2 rectal cancer patients, treated with CMT followed by surgical
      resection, between 1998 and 2003. Preoperative clinicopathologic factors
      determined by biopsy, ERUS, proctoscopy, and digital rectal examination were
      correlated with the degree of downstaging of the primary mural lesion (tumor
      downstaging) in response to neoadjuvant therapy. Associations were analyzed by
      chi-square, Kaplan-Meier, and logistic regression. RESULTS: Of 274 patients, 51%
      obtained tumor downstaging in response to preoperative treatment, i.e., lower
      pathologic T-stage compared with pretreatment ERUS. Five-year recurrence-free
      survival was 89% in the cohort that obtained tumor downstaging compared with only
      45% in the cohort that obtained no tumor downstaging. Factors significantly
      associated with limited or lack of tumor downstaging after CMT included: fixed
      tumor on digital rectal examination (p < 0.021), near-circumferential tumor (p <
      0.011), tumor stenosis (p < 0.025), metastatic disease (p < 0.012), biopsy-proven
      poorly differentiated pathology (p < 0.002), and radial extension >2.5 mm on ERUS
      (p < 0.031). On multivariate analysis, deep radial extension on ERUS, metastatic
      disease, and poorly differentiated pathology were in each, independently
      associated with limited or lack of tumor downstaging. CONCLUSIONS: Pretreatment
      evaluation with biopsy, proctoscopy, and ERUS can identify T3 rectal cancer
      patients unlikely to respond well to CMT. These patients may be considered for
      alternative protocols and their tumors studied to ascertain the molecular events
      responsible for resistance to chemoradiation.

PMID- 18046562
TI  - NF-kappaB-dependent synergistic regulation of CXCL10 gene expression by IL-1beta
      and IFN-gamma in human intestinal epithelial cell lines.
AB  - BACKGROUND AND AIMS: Little is known about the intestinal epithelial expression
      and secretion of CXCL10 (IP-10), a chemokine involved in recruiting T cells and
      monocytes. We aimed to study CXCL10 gene expression and regulation by the pro
      inflammatory cytokines interleukin (IL)-1beta, interferon (IFN)-gamma and tumour
      necrosis factor (TNF)-alpha in intestinal epithelial cell lines. MATERIALS AND
      METHODS: CXCL10 expression and secretion kinetics were assessed in Caco-2, HT-29
      and DLD1 human colon epithelial cells, treated with IL-1beta, TNF-alpha, IFN
      gamma alone or in combination with each other by real-time polymerase chain
      reaction (PCR), Northern blotting and enzyme-linked immunoabsorbent assay
      (ELISA). Transient transfections with TGL-IP10 (CXCL10 promoter) and TGL-IP10
      kappaB2 mutant promoter and gelshifts and supershifts for nuclear factor (NF)
      kappaB were also performed. RESULTS: Real-time PCRs and ELISA experiments
      revealed that IL-1beta was the strongest and earliest inducer of CXCL10 messenger
      ribonucleic acid (mRNA) expression and protein secretion in Caco-2 cell line,
      whereas INF-gamma had a delayed kinetics. There was a strong synergistic effect
      of either TNF-alpha or IL-1beta with IFN-gamma both on CXCL10 mRNA expression and
      protein secretion in all three cell lines. Real-time PCR and ELISA experiments
      using a specific NF-kappaB inhibitor and transfection experiments with a NF
      kappaB-binding defective CXCL10 promoter construct revealed that the induction of
      CXCL10 by IL-1beta and its synergism with IFN-gamma is NF-kappaB dependent.
      CONCLUSION: These data demonstrate that in colonic epithelial cells, depending on
      the cellular context and utilizing the NF-kappaB pathway, IL-1beta alone and/or
      in synergism with IFN-gamma may play a major role in the induction of CXCL10.

PMID- 18046563
TI  - Lipogranuloma of the cervix in a postmenopausal patient with a uterine prolapse.
AB  - OBJECTIVE: Lipogranuloma is a rare inflammatory reactive process related to
      exogenous or endogenous lipids with an admission to the dermis and subcutis. It
      is described most frequently in the penis and scrotum of young adults.
      Lipogranuloma of the female genitalia is a rather uncommon condition. The lesion
      is histopathologically characterized by fat vacuoles with foreign body type giant
      cells and scattered lymphocytes. CASE: We described an incidental lipogranuloma
      of the cervix in a 60-year-old woman who presented with total uterine prolapse.
      CONCLUSION: Although lipogranuloma mostly occurs in young male patients,
      especially in the genital tract, clinicians should be aware of this entity in the
      cervix of a postmenopausal woman with uterine prolapse, which may challenge the
      differential clinical diagnosis.

PMID- 18046564
TI  - The evaluation of endometrial tumors by transvaginal and Doppler ultrasonography.
AB  - BACKGROUND: Endometrial cancer is the most common malignancy of the female
      genital tractus which is primarily seen in postmenopausal women. The purpose of
      this study is to investigate the relation between uterine histopathologic
      alterations and sonographic findings in women diagnosed with endometrial cancer.
      MATERIALS AND METHODS: A total of 120 women who were histologically diagnosed
      with endometrial cancer and who admitted to Gynecologic Oncology Department in
      the study center were eligible. The subjects were evaluated by Doppler
      ultrasonography (USG) coupled with a vaginal probe before surgery. After surgical
      staging was performed in all participants, the preoperative sonographic findings
      were compared with histopathologic information yielded from surgical specimens.
      RESULTS: The mean age of the study population was 53.1 years. About 85% of the
      subjects were postmenopausal. The mean endometrial thickness measured by
      transvaginal USG was found to be 25.6 +/- 13.4 mm (range 6-88 mm). The diagnostic
      accuracy, sensitivity, specificity, positive and negative predictive values of
      transvaginal USG was, respectively, 69, 66, 72, 60 and 75%. In 37 (30.8%)
      patients, transvaginal USG could not correctly predict the depth of myometrial
      invasion. Myometrial invasion was underestimated in 17 cases (14.2%) and
      overestimated in 20 cases (16.7%). There was a significant negative correlation
      between the tumor grade and uterine artery blood flow. CONCLUSIONS: The results
      of the present study determine that transvaginal USG has moderate sensitivity and
      moderate-to-high specificity which limit its use. However, endometrial thickness,
      myometrial invasion and resistance index values determined by Doppler USG can
      indicate the tumor grade allowing individualized treatment to be planned for
      endometrial tumors.

PMID- 18046565
TI  - Recurrent respiratory papillomatosis: an overview of current thinking and
      treatment.
AB  - Human papillomaviruses (HPV) infection in benign laryngeal papillomas is well
      established. The vast majority of recurrent respiratory papillomatosis lesions
      are due to HPV types 6 and 11. Human papillomaviruses are small non-enveloped
      viruses (>8 kb), that replicate within the nuclei of infected host cells.
      Infected host basal cell keratinocytes and papillomas arise from the disordered
      proliferation of these differentiating keratinocytes. Surgical debulking of
      papillomas is currently the treatment of choice; newer surgical approaches
      utilizing microdebriders are replacing laser ablation. Surgery aims to secure an
      adequate airway and improve and maintain an acceptable quality of voice. Adjuvant
      treatments currently used include cidofovir, indole-3-carbinol, ribavirin, mumps
      vaccine, and photodynamic therapy. The recent licensing of prophylactic HPV
      vaccines is a most interesting development. The low incidence of RRP does pose
      significant problems in recruitment of sufficient numbers to show statistical
      significance. Large multi-centre collaborative clinical trials are therefore
      required. Even so, sufficient clinical follow-up data would take several years.

PMID- 18046566
TI  - Surgical treatment of the high jugular bulb by compressing sinus sigmoideus: two
      cases.
AB  - If the jugular bulb normally surrounded by a bony layer in jugular fossa is
      anatomically over the inferior surface of the bony annulus, in the middle ear or
      over the basal turn of cochlea, it is then named as high jugular bulb (HJB). It
      may be dehiscent or aberrant. It is reported to occur in 5% of the temporal bone
      specimens. In accordance with the literature jugular bulb compression, jugular
      vein ligation and embolization are suggested in such cases. In both of the
      presented cases, there was bleeding from jugular bulb during surgery and jugular
      bulb was compressed with bone wax and Surgicel, but sigmoid sinus has been
      compressed after failure to stop bleeding through jugular bulb compression.
      Venous MR angiographies showed no flow in postoperative controls. Although it is
      very rarely seen clinically, we present two HJB cases and different treatment
      perspectives accompanied by literature.

PMID- 18046567
TI  - Early onset otitis media: risk factors and effects on the outcome of chronic
      suppurative otitis media.
AB  - The onset of early otitis media (EOM), in the first few months of life has been
      reported to predict later chronic otitis media (CSOM), although the prevalence
      rates are increasing little is known about specific risk factors. In this survey
      we examined the hypothesis that higher risk factors is associated with the
      development of OM within 1 year compared to later onset and early onset otitis
      media (OM) has potential for negative outcome of CSOM. This is a survey of the
      age at onset of otorrhoea and associated risk factors in children with CSOM, in
      five sites spread in two sub-urban cities in two states in Nigeria.
      Questionnaires were administered on the informants followed by examination of the
      children. EOM was seen in 136/189 (70%) with CSOM, the age range was 1-150
      months, mean of 59.25 (SD = 44.55). Of the 85 CSOM subjects with hearing loss,
      EOM accounted for 49 (57.7%) while 36 (42.4%) was later onset, On multivariate
      analysis (OR = 0.276, CI = 0.133-0.572, P = 0.001) revealing EOM was significant
      in the development of hearing loss however there was no correlation with the
      frequency of attack of otorrhoea (OR = 1.025, CI = 0.88-1.19, P = 0.75). Low
      socioeconomic status seen in 110/136 EOM (P = 0.000), allergy (P = 0.030) and
      number of people >10 in household (OR = 4.13, CI = 1.81-9.39, P = 0.001)
      constituted the significant risk for EOM compared to later onset. Bottlefeeding,
      adenoiditis/adenoid hypertrophy, indoor cooking and upper respiratory infection
      were not found to have statistical significance in early onset OM compared to
      later onset OM. This study found correlation between EOM and hearing loss and
      identified allergy, low social status and chronic exposure to overcrowding
      through increased number of children in the household significant risk factors
      for future research focus. This may help in controlling the prevalence of hearing
      loss accompanying CSOM.

PMID- 18046568
TI  - In vivo modeling of polysumoylation uncovers targeting of Topoisomerase II to the
      nucleolus via optimal level of SUMO modification.
AB  - Conjugation of SUMO to target proteins is an essential eukaryotic regulatory
      pathway. Multiple potential SUMO substrates were identified among nuclear and
      chromatin proteins by proteomic approaches. However, the functional roles of SUMO
      modified pools of individual proteins remain largely obscure, as only a small
      fraction of a given target is sumoylated and therefore is experimentally
      inaccessible. To overcome this technical difficulty in case of Topoisomerase II,
      we employed constitutive SUMO modification, enabling tracking of modified Top2p,
      not only biochemically but also cytologically and genetically. Topoisomerase II
      fused to a critical number of SUMO repeats is concentrated at the specific
      intranuclear domain, the nucleolus, when more than four SUMO moieties are added,
      indicating that fused SUMO repeats are biologically active. Further analysis has
      established that poly-sumoylation of Top2p is required for the stable maintenance
      of the nucleolar organizer, linking SUMO-mediated targeting to functional
      maintenance of ribosomal RNA gene cluster.

PMID- 18046569
TI  - Fluorescence in situ hybridization (FISH) on maize metaphase chromosomes with
      quantum dot-labeled DNA conjugates.
AB  - Semiconductor nanocrystals, also called quantum dots (QDs), are novel inorganic
      fluorophores which are brighter and more photostable than organic fluorophores.
      In the present study, highly dispersive QD-labeled oligonucleotide (TAG)(8) (QD
      deoxyribonucleic acid [DNA]) conjugates were constructed via the metal-thiol
      bond, which can be used as fluorescence in situ hybridization (FISH) probes. FISH
      analysis of maize metaphase chromosomes using the QD-DNA probes showed that the
      probes could penetrate maize chromosomes and nuclei and solely hybridized to
      complementary target DNAs. Compared with the conventional organic dyes such as
      Cy3 and fluorescein isothiocyanate, this class of luminescent labels bound with
      oligonucleotides is brighter and more stable against photobleaching on the
      chromosomes after FISH. These results suggest that QD fluorophores may be a more
      stable and useful fluorescent label for FISH applications in plant chromosome
      mapping considering their size-tunable luminescence spectra.

PMID- 18046570
TI  - Poor binocular coordination of saccades in dyslexic children.
AB  - AIM: To examine the quality of binocular coordination of saccades in dyslexic
      children in single word reading and in a task requiring fixation of single LED.
      METHODS: Eighteen children with dyslexia (11.4 +/- 2 years old) and 13 non
      dyslexic children of matched age were studied. Horizontal saccades from both eyes
      were recorded with a photoelectric system (Oculomotor-Bouis). RESULTS: Binocular
      coordination during and after the saccade in dyslexics is worse than that of non
      dyslexic children; the disconjugacy does not depend on the condition. Moreover,
      dyslexics do not show the stereotyped pattern of disconjugacy (divergence during
      the saccade and convergence after the saccade). The conjugate post-saccadic drift
      is larger in dyslexics for both conditions. CONCLUSION: Poor quality of binocular
      coordination of saccades and drift of the eyes after the saccade, regardless of
      the task, indicates an intrinsic ocular motor deficiency. Such a deficiency could
      be related to immaturity of the normal ocular motor learning mechanisms via which
      ocular motor coordination and stable fixation are achieved. Learning could be
      based on the interaction between the saccade and vergence subsystems. The
      cerebellum, but also cortical areas of the magnocellular stream such as the
      parietal cortex, could be the sites of ocular motor learning.

PMID- 18046572
TI  - Celebration of the 50th anniversary of publication of Histochemistry and Cell
      Biology.

PMID- 18046573
TI  - Quantitative investigations of electrical nerve excitation treated as
      polarization. 1907.

PMID- 18046571
TI  - Nucleolus: the fascinating nuclear body.
AB  - Nucleoli are the prominent contrasted structures of the cell nucleus. In the
      nucleolus, ribosomal RNAs are synthesized, processed and assembled with ribosomal
      proteins. RNA polymerase I synthesizes the ribosomal RNAs and this activity is
      cell cycle regulated. The nucleolus reveals the functional organization of the
      nucleus in which the compartmentation of the different steps of ribosome
      biogenesis is observed whereas the nucleolar machineries are in permanent
      exchange with the nucleoplasm and other nuclear bodies. After mitosis, nucleolar
      assembly is a time and space regulated process controlled by the cell cycle. In
      addition, by generating a large volume in the nucleus with apparently no RNA
      polymerase II activity, the nucleolus creates a domain of retention/sequestration
      of molecules normally active outside the nucleolus. Viruses interact with the
      nucleolus and recruit nucleolar proteins to facilitate virus replication. The
      nucleolus is also a sensor of stress due to the redistribution of the ribosomal
      proteins in the nucleoplasm by nucleolus disruption. The nucleolus plays several
      crucial functions in the nucleus: in addition to its function as ribosome factory
      of the cells it is a multifunctional nuclear domain, and nucleolar activity is
      linked with several pathologies. Perspectives on the evolution of this research
      area are proposed.

PMID- 18046574
TI  - Redirection of the phenylpropanoid pathway to feruloyl malate in Arabidopsis
      mutants deficient for cinnamoyl-CoA reductase 1.
AB  - Cinnamoyl-CoA reductase 1 (CCR1, gene At1g15950) is the main CCR isoform implied
      in the constitutive lignification of Arabidopsis thaliana. In this work, we have
      identified and characterized two new knockout mutants for CCR1. Both have a dwarf
      phenotype and a delayed senescence. At complete maturity, their inflorescence
      stems display a 25-35% decreased lignin level, some alterations in lignin
      structure with a higher frequency of resistant interunit bonds and a higher
      content in cell wall-bound ferulic esters. Ferulic acid-coniferyl alcohol ether
      dimers were found for the first time in dicot cell walls and in similar levels in
      wild-type and mutant plants. The expression of CCR2, a CCR gene usually involved
      in plant defense, was increased in the mutants and could account for the
      biosynthesis of lignins in the CCR1-knockout plants. Mutant plantlets have three
      to four-times less sinapoyl malate (SM) than controls and accumulate some
      feruloyl malate. The same compositional changes occurred in the rosette leaves of
      greenhouse-grown plants. By contrast and relative to the control, their stems
      accumulated unusually high levels of both SM and feruloyl malate as well as more
      kaempferol glycosides. These findings suggest that, in their hypolignified stems,
      the mutant plants would avoid the feruloyl-CoA accumulation by its redirection to
      cell wall-bound ferulate esters, to feruloyl malate and to SM. The formation of
      feruloyl malate to an extent far exceeding the levels reported so far indicates
      that ferulic acid is a potential substrate for the enzymes involved in SM
      biosynthesis and emphasizes the remarkable plasticity of Arabidopsis
      phenylpropanoid metabolism.

PMID- 18046576
TI  - Characterization of trimeric acetylcholinesterase from a legume plant,
      Macroptilium atropurpureum Urb.
AB  - We recently identified plant acetylcholinesterases (E.C.3.1.1.7; AChEs)
      homologous to the AChE purified from a monocotyledon, maize, that are distinct
      from the animal AChE family. In this study, we purified, cloned and characterized
      an AChE from a dicotyledon, siratro. The full-length cDNA of siratro AChE is
      1,441 nucleotides, encoding a 382-residue protein that includes a signal peptide.
      This AChE is a disulfide-linked 125-kDa homotrimer consisting of 41-42 kDa
      subunits, in contrast to the maize AChE, which exists as a mixture of disulfide
      and non-covalently linked 88-kDa homodimers. The plant AChEs apparently consist
      of various quaternary structures, depending on the plant species, similar to the
      animal AChEs. We compared the enzymatic properties of the dimeric maize and
      trimeric siratro AChEs. Similar to electric eel AChE, both plant AChEs hydrolyzed
      acetylthiocholine (or acetylcholine) and propionylthiocholine (or
      propionylcholine), but not butyrylthiocholine (or butyrylcholine), and their
      specificity constant was highest against acetylcholine. There was no significant
      difference between the enzymatic properties of trimeric and dimeric AChEs,
      although two plant AChEs had low substrate turnover numbers compared with
      electric eel AChE. The two plant AChE activities were not inhibited by excess
      substrate concentrations. Thus, similar to some plant AChEs, siratro and maize
      AChEs showed enzymatic properties of both animal AChE and animal BChE. On the
      other hand, both siratro and maize AChEs exhibited low sensitivity to the AChE
      specific inhibitor neostigmine bromide, dissimilar to other plant AChEs. These
      differences in enzymatic properties of plant AChEs may reflect the phylogenetic
      evolution of AChEs.

PMID- 18046575
TI  - Physiological roles of plant glycoside hydrolases.
AB  - The functions of plant glycoside hydrolases and transglycosidases have been
      studied using different biochemical and molecular genetic approaches. These
      enzymes are involved in the metabolism of various carbohydrates containing
      compounds present in the plant tissues. The structural and functional diversity
      of the carbohydrates implies a vast spectrum of enzymes involved in their
      metabolism. Complete genome sequence of Arabidopsis and rice has allowed the
      classification of glycoside hydrolases in different families based on amino acid
      sequence data. The genomes of these plants contain 29 families of glycoside
      hydrolases. This review summarizes the current research on plant glycoside
      hydrolases concerning their principal functional roles, which were attributed to
      different families. The majority of these plant glycoside hydrolases are involved
      in cell wall polysaccharide metabolism. Other functions include their
      participation in the biosynthesis and remodulation of glycans, mobilization of
      energy, defence, symbiosis, signalling, secondary plant metabolism and metabolism
      of glycolipids.

PMID- 18046577
TI  - A monoclonal antibody that inhibits Trypanosoma cruzi growth in vitro and its
      reaction with intracellular triosephosphate isomerase.
AB  - In parasites of the order Kinetoplastida, such as Trypanosoma cruzi and
      Trypanosoma brucei, glycolysis is carried out by glycolytic enzymes in
      glycosomes. One of the glycolytic enzymes is triosephosphate isomerase (TIM),
      which in T. brucei is localized exclusively in glycosomes, whereas in T. cruzi,
      the localization of TIM has not been fully ascertained. In the present work, we
      made a monoclonal antibody (mAb 6-11G) against recombinant T. cruzi TIM (rTcTIM).
      Incubation of T. cruzi epimastigotes with the mAb inhibited parasite survival.
      Western blotting showed that the mAb recognized rTcTIM and a 27 kDa band in T.
      cruzi lysates that corresponded to TcTIM. Sera from patients with Chagas disease
      recognized rTcTIM and cross-reacted with human recombinant TIM. The cross
      reactivity between parasite and human TIM possibly contributes to the autoimmune
      pathogenesis of Chagas disease. Electron microscopy of T. cruzi epimastigotes
      with the mAb showed that TIM was located within glycosomes, in the cytoplasm, the
      nucleus, and the kinetoplast. Collectively, the data shed new light on T. cruzi
      TIM and opens perspectives for drug design.

PMID- 18046578
TI  - Chemical composition and larvicidal properties of the essential oils from Drimys
      brasiliensis Miers (Winteraceae) on the cattle tick Rhipicephalus (Boophilus)
      microplus and the brown dog tick Rhipicephalus sanguineus.
AB  - The essential oil obtained from leaves and stem barks of the Southern Brazilian
      native Drimys brasiliensis Miers, a tree with medicinal properties, was analyzed
      by gas chromatography (GC) and GC/mass spectrometry (MS). The oil was
      characterized by sesquiterpenoids (66%), cyclocolorenone being the most abundant
      (30.4%), followed by bicyclogermacrene (11.8%) and alpha-gurjunene (6.0%).
      Laboratory tests were carried out to determine the toxicity of the essential oil
      on larvae of the cattle tick Rhipicephalus (Boophilus) microplus and the brown
      dog tick Rhipicephalus sanguineus by the larval immersion test. It was observed
      that the oil was lethal, killing 100% of the larvae of both ticks at the doses of
      25, 12.5, and 6.25 microl/ml. The lowest dose tested, 3.125 microl/ml, was also
      toxic, killing 95-98% of the larvae.

PMID- 18046580
TI  - Co-localization and unique distributions of two clock proteins CYCLE and CLOCK in
      the cephalic ganglia of the ground cricket, Allonemobius allardi.
AB  - CYCLE (CYC) and CLOCK (CLK) are transcriptional activators of the circadian clock
      genes, period (per) and timeless (tim), binding at E-boxes of their upstream
      regulatory region in Drosophila. CYC-like and CLK-like immunohistochemical
      reactivities (CYC-ir and CLK-ir) were investigated in the ground cricket,
      Allonemobius allardi, in which immunohistochemical reactivities for three
      circadian clock proteins (PERIOD, Doubletime, and Cryptochrome), two
      neuropeptides (crustacean cardioactive peptide and diapause hormone), and
      arylalkylamine-N-acetyltransferase had previously been mapped in the brain
      subesophageal ganglion (SOG) complex. CYC-ir and CLK-ir occurred predominantly in
      the cytoplasm of the neurons distributed mainly in the central brain, SOG, and
      corpora cardiaca. Double-labeling experiments showed that CYC-ir and CLK-ir were
      co-localized only in the mandibular and maxillary neuromeres of the SOG. The
      neuronal processes in the dorsolateral region of the protocerebrum partially
      shared the immunoreactivities, whereas most of the other immunoreactivities were
      unique. The optic lobe showed reactivity to anti-CYC at small proximal
      frontodorsal cells and to anti-CLK at small proximal frontoventral cells. The
      frontal ganglion exhibited CYC-ir in the cell bodies that lacked CLK-ir. No
      difference in their number, distribution, or staining intensity was found between
      sampling under light:dark regimes of 16:8 and 12:12. The levels of both CYC-ir
      and CLK-ir showed no oscillation throughout a 24-h period. The co-localization
      pattern suggests that the midline cells of the SOG share most of the circadian
      related immunoreactivities, thus constituting the heart of the circadian clock in
      A. allardi.

PMID- 18046579
TI  - Activation of stem cells in hepatic diseases.
AB  - The liver has enormous regenerative capacity. Following acute liver injury,
      hepatocyte division regenerates the parenchyma but, if this capacity is
      overwhelmed during massive or chronic liver injury, the intrinsic hepatic
      progenitor cells (HPCs) termed oval cells are activated. These HPCs are
      bipotential and can regenerate both biliary epithelia and hepatocytes. Multiple
      signalling pathways contribute to the complex mechanism controlling the behaviour
      of the HPCs. These signals are delivered primarily by the surrounding
      microenvironment. During liver disease, stem cells extrinsic to the liver are
      activated and bone-marrow-derived cells play a role in the generation of fibrosis
      during liver injury and its resolution. Here, we review our current understanding
      of the role of stem cells during liver disease and their mechanisms of
      activation.

PMID- 18046582
TI  - Lymphoepithelioma-like thymic carcinoma in a 16-year-old boy with nephrotic
      syndrome--a case report.
AB  - Nephrotic syndrome can occur as a consequence of, among others, malignancy. In
      this report we describe a 16-year-old boy with secondary nephrotic syndrome
      associated with lymphoepithelioma-like thymic carcinoma, an extremely rare
      subtype ofthymic carcinoma with poor prognosis.

PMID- 18046581
TI  - Chronic kidney disease mineral and bone disorder in children.
AB  - Childhood and adolescence are crucial times for the development of a healthy
      skeletal and cardiovascular system. Disordered mineral and bone metabolism
      accompany chronic kidney disease (CKD) and present significant obstacles to
      optimal bone strength, final adult height, and cardiovascular health. Decreased
      activity of renal 1 alpha hydroxylase results in decreased intestinal calcium
      absorption, increased serum parathyroid hormone levels, and high-turnover renal
      osteodystrophy, with subsequent growth failure. Simultaneously, phosphorus
      retention exacerbates secondary hyperparathyroidism, and elevated levels
      contribute to cardiovascular disease. Treatment of hyperphosphatemia and
      secondary hyperparathyroidism improves growth and high-turnover bone disease.
      However, target ranges for serum calcium, phosphorus, and parathyroid hormone
      (PTH) levels vary according to stage of CKD. Since over-treatment may result in
      adynamic bone disease, growth failure, hypercalcemia, and progression of
      cardiovascular calcifications, therapy must be carefully adjusted to maintain
      optimal serum biochemical parameters according to stage of CKD. Newer therapeutic
      agents, including calcium-free phosphate binding agents and new vitamin D
      analogues, effectively suppress serum PTH levels while limiting intestinal
      calcium absorption and may provide future therapeutic alternatives for children
      with CKD.

PMID- 18046583
TI  - Non-native Ambrosia pollen in the atmosphere of Rzeszow (SE Poland); evaluation
      of the effect of weather conditions on daily concentrations and starting dates of
      the pollen season.
AB  - The investigated problem was whether and to what an extent the elements of
      weather conditions were associated with changes in the concentration of Ambrosia
      pollen in air. The study was carried out in the years 1997-2004 using the
      volumetric method. Ragweed did not occur in the flora of the town of Rzeszow and
      its vicinity, but every year its pollen occurred at concentrations considerably
      exceeding the threshold values for the allergic response. The pollen seasons
      usually began from near the end of August to the first part of September. The
      values of daily concentrations varied greatly: days without pollen grains being
      frequently noted while single grains occurred long before and after the season.
      The effect of the elements of weather on changes in the concentration of pollen
      in the air was slight. Taking into account all meteorological parameters, it can
      be stated that an increase in the number of pollen grains is connected with
      increased temperature and higher wind speeds, but negatively correlated with
      humidity and rainfall. These relationships can usually be explained by the
      effects of the type of weather taking place over the wider region. The analysis
      of the results showed that pollen was probably transported from distant regions.
      The mean angle at which the greatest pollen concentrations were recorded
      corresponded to the SE wind direction. The analysis of synoptic phenomena during
      the pollen season confirms the thesis about the long-distance transport from the
      south, southeast and southwest. A close dependence was also found between the
      starting date of the season and the sum of maximum temperatures and the sum of
      differences between the maximum and minimum temperatures.

PMID- 18046584
TI  - Ceratobasidiaceae mycorrhizal fungi isolated from nonphotosynthetic orchid
      Chamaegastrodia sikokiana.
AB  - Mycorrhizal fungi were isolated from the nonphotosynthetic orchid Chamaegastrodia
      sikokiana and identified as members of Ceratobasidiaceae by phylogenetic analysis
      of the internal transcribed spacer (ITS) region of ribosomal deoxyribonucleic
      acid. The ITS sequences were similar among geographically separated samples
      obtained from Mt. Kiyosumi in Chiba Prefecture and Mt. Yokokura in Kochi
      Prefecture. One of the isolated fungi, KI1-2, formed ectomycorrhiza on seedlings
      of Abies firma in pot culture, suggesting that tripartite symbiosis exists among
      C. sikokiana, mycorrhizal fungi, and A. firma in nature, and carbon compounds are
      supplied from A. firma to C. sikokiana through the hyphae of the mycorrhizal
      fungi. To our knowledge, this is the second study to suggest the involvement of
      Ceratobasidiaceae fungi in tripartite symbiosis with achlorophyllous orchids and
      photosynthetic host plants.

PMID- 18046585
TI  - Spontaneous infective spondylitis and mycotic aneurysm: incidence, risk factors,
      outcome and management experience.
AB  - Infective spondylitis occurring concomitantly with mycotic aneurysm is rare. A
      retrospective record review was conducted in all cases of mycotic aneurysm from
      January 1995 to December 2004, occurring in a primary care and tertiary referral
      center. Spontaneous infective spondylitis and mycotic aneurysm were found in six
      cases (10.3% of 58 mycotic aneurysm patients). Neurological deficit (50% vs. 0; P
      < 0.001) is the significant clinical manifestation in patients with spontaneous
      infective spondylitis and mycotic aneurysm. The presence of psoas abscess on
      computed tomography (83.3% vs. 0; P < 0.001) and endplate destruction on
      radiography (50% vs. 0; P < 0.001) are predominated in patients with spontaneous
      infective spondylitis and mycotic aneurysm. Of these six patients, four with
      Salmonella infection received surgical intervention and all survived. Another two
      patients (one with Streptococcus pyogenes, another with Staphylococcus aureus)
      received conservative therapy and subsequently died from rupture of aneurysm or
      septic shock. Paravertebral soft tissue swelling, presence of psoas abscess
      and/or unclear soft tissue plane between the aorta and vertebral body in relation
      to mycotic aneurysm may indicate a concomitant infection in the spine. In
      contrast, if prevertebral mass is found in the survey of spine infection,
      coexisting mycotic aneurysm should be considered.

PMID- 18046586
TI  - Pure manganese(III) 5,10,15,20-tetrakis(4-benzoic acid)porphyrin (MnTBAP) is not
      a superoxide dismutase mimic in aqueous systems: a case of structure-activity
      relationship as a watchdog mechanism in experimental therapeutics and biology.
AB  - Superoxide is involved in a plethora of pathological and physiological processes
      via oxidative stress and/or signal transduction pathways. Superoxide dismutase
      (SOD) mimics have, thus, been actively sought for clinical and mechanistic
      purposes. Manganese(III) 5,10,15,20-tetrakis(4-benzoic acid)porphyrin (MnTBAP) is
      one of the most intensely explored "SOD mimics" in biology and medicine. However,
      we show here that this claimed SOD activity of MnTBAP in aqueous media is not
      corroborated by comprehensive structure-activity relationship studies for a wide
      set of Mn porphyrins and that MnTBAP from usual commercial sources contains
      different amounts of noninnocent trace impurities (Mn clusters), which inhibited
      xanthine oxidase and had SOD activity in their own right. In addition, the
      preparation and thorough characterization of a high-purity MnTBAP is presented
      for the first time and confirmed that pure MnTBAP has no SOD activity in aqueous
      medium. These findings call for an assessment of the relevance and suitability of
      using MnTBAP (or its impurities) as a mechanistic probe and antioxidant
      therapeutic; conclusions on the physiological and pathological role of superoxide
      derived from studies using MnTBAP of uncertain purity should be examined
      judiciously. An unequivocal distinction between the biological effects due to
      MnTBAP and that of its impurities can only be unambiguously made if a pure sample
      is/was used. This work also illustrates the contribution of fundamental structure
      activity relationship studies not only for drug design and optimization, but also
      as a "watchdog" mechanism for checking/spotting eventual incongruence of drug
      activity in chemical and biological settings.

PMID- 18046587
TI  - Fluorescence resonance energy transfer in ferritin labeled with multiple
      fluorescent dyes.
AB  - We simultaneously labeled ferritin with two Alexa Fluor fluorophores (AF350 and
      AF430). When both fluorophores label the same ferritin subunit, fluorescence
      resonance energy transfer (FRET) takes place from the excited AF350 to the
      acceptor AF430. By varying the number and the ratio of labeling fluorophores, we
      can modulate FRET such that the ferritin particles can exhibit multiple colors
      under UV illumination. Labeling of the ferritin shell does not affect the
      properties of the metallic core.

PMID- 18046589
TI  - Unusual acute formed gastric bezoars due to plaster ingestion successfully
      treated by gastric irrigation: report of two cases.
AB  - Bezoars usually present as a mass in the stomach. One of the uncommon causes of
      bezoars is ingestion of plaster in a suicidal attempt. We present here two
      patients with acute formed gastric bezoars due to plaster ingestion. Their main
      complaints were abdominal pain, nausea, and vomiting. Clinical examination
      revealed a slightly distended abdomen and a palpable mass in the epigastric
      region. Plain abdominal radiograph showed plaster casts in the stomach. They were
      successfully treated by insertion of a nasogastric tube and gastric irrigation
      using saline solution over 24 h. Post-treatment abdominal X-ray showed dissolved
      plaster passing through the small intestines and the colon. The treatment course
      was uneventful, and finally patients were discharged with good condition and
      referred to a psychiatric clinic for treatment of underlying psychological
      disorder.

PMID- 18046588
TI  - Natural killer cells and alterations in collagen density: signs of periradicular
      herpesvirus infection?
AB  - This study evaluated the presence and density of natural killer (NK) cells as
      well as collagen density in chronic apical periodontitis lesions and tried to
      find any correlations with concomitant herpesvirus infection or histopathological
      status of the lesion. Surgical specimens of chronic apical periodontitis lesions
      were surveyed for the presence and density of NK cells by immunohistochemical
      analysis. Collagen density in these lesions was quantified by means of
      histochemistry. All specimens were positive for the presence of CD57-positive
      cells. Topographically, CD57-positive cells were found singly or forming clusters
      in the granulomatous tissue, as well as subjacent and within the cystic
      epithelium. No significant differences in the density of CD57-positive cells were
      found between nonepithelialized and epithelialized lesions or between herpesvirus
      positive and herpesvirus-negative lesions. Significant differences were found in
      volumetric density of collagen when comparing nonepithelialized and
      epithelialized lesions, with the latter demonstrating higher values. When no
      distinction of lesion type was made, there was no significant difference in
      collagen density between herpesvirus-positive and herpesvirus-negative lesions.
      When comparing the collagen density in herpesvirus-positive and herpesvirus
      negative specimens from the same lesion type, a significant difference was found
      in nonepithelialized lesions, with herpesvirus-positive lesions showing lower
      values. The presence of CD57-positive cells in all chronic apical periodontitis
      specimens may indicate that activated NK cells play a role in the pathogenesis of
      this disease, possibly by participating in innate immunity events involved in the
      control of virus infection. Collagen density may vary in function of the type of
      lesion and presence of herpesvirus infection.

PMID- 18046590
TI  - Optimization of process parameters for the production of carbonyl reductase by
      Candida viswanathii in a laboratory-scale fermentor.
AB  - The effect of pH, aeration and mixing on the growth and production of carbonyl
      reductase by Candida viswanathii was investigated in a 6.6-l fermentor.
      Controlling the pH at 8.0 had a very significant effect on the enzyme production.
      Aeration and agitation influenced the dissolved oxygen concentration which in
      turn affected growth as well as enzyme production. A maximum carbonyl reductase
      activity (53 Umg(-1)) was attained in 24 h under the optimal cultivation
      conditions of controlled pH at 8.0, aeration rate 1 vvm and an agitation speed of
      250 rpm at 25 degrees C. The enzyme activity was twice as high (56 Umg(-1)) in
      the fermentor as compared to a shake flask. Further, the duration of growth and
      enzyme production in the fermentor was shortened. Cells cultivated under the
      optimized conditions were used for the preparative scale reduction of N, N
      dimethyl-(3-keto)-2-thienyl-propanamine to (S)-N, N-dimethyl-(3-hydroxy)-2
      thienyl-propanamine, a key intermediate in the production of the important
      antidepressant drug (S)-duloxetine.

PMID- 18046591
TI  - Biexponential and diffusional kurtosis imaging, and generalised diffusion-tensor
      imaging (GDTI) with rank-4 tensors: a study in a group of healthy subjects.
AB  - OBJECT: Clinical diffusion imaging is based on two assumptions of limited
      validity: that the radial projections of the diffusion propagator are Gaussian,
      and that a single directional diffusivity maximum exists in each voxel. The
      former can be removed using the biexponential and diffusional kurtosis models,
      the latter using generalised diffusion-tensor imaging. This study provides
      normative data for these three models. MATERIALS AND METHODS: Eighteen healthy
      subjects were imaged. Maps of the biexponential parameters D (fast), D (slow) and
      f (slow), of D and K from the diffusional kurtosis model, and of diffusivity D'
      were obtained. Maps of generalised anisotropy (GA) and scaled entropy(SE) were
      also generated, for second and fourth rank tensors. Normative values were
      obtained for 26 regions. RESULTS: In grey versus white matter, D (slow) and D'
      were higher and D (fast), f (slow) and K were lower. With respect to maps of D',
      anatomical contrast was stronger in maps of D (slow) and K. Elevating tensor rank
      increased SE, generally more significantly than GA, in: anterior limb of internal
      capsule, corpus callosum, deep frontal and subcortical white matter, along
      superior longitudinal fasciculus and cingulum. CONCLUSION: The values reported
      herein can be used for reference in future studies and in clinical settings.

PMID- 18046592
TI  - Is it time to standardize ethics guiding the peer review process?
AB  - While most scientific journals have well defined ethics requirements for authors,
      very few journals explicitly specify the ethics standards that govern the actions
      of editors, editorial board members, and reviewers. We believe it is time to
      create a standardized policy for all medical and scientific journals that guides
      the ethical conduct of all stakeholders in the peer review process.

PMID- 18046593
TI  - A reliable biomarker derived from plasmalogens to evaluate malignancy and
      metastatic capacity of human cancers.
AB  - Antigen tumor markers employed in monitoring therapeutical approaches are limited
      by their specificity (Sp) and sensitivity (Se). The aim of this study was to
      investigate the suitability of a lipid tumor marker derived from ether-linked
      phospholipids and to compare it with others usually assayed in clinical practice.
      Complex lipids from normal and pathological breast, lung, and prostate tissue
      were isolated and analyzed by TLC and c-GLC methods. Results were compared as
      pooled samples, or by means of the averaged percent changes with respect to the
      composition observed in the normal tissue of the same patient. Sp, Se, negative
      predictive (NPV) and positive- predictive values (PPV) were established for
      conventional markers and for the proposed lipid-derived marker. Results
      demonstrated that the content of monoenoic fatty acyl chains was significantly
      increased in total lipids, phosphatidylethanolamine, and especially in
      ethanolamine-containing ether lipids of neoplastic tissues with respect to their
      corresponding normal ones. Major changes were observed in the plasmalogen sub
      fraction where the ratio monoenoic/saturated fatty acids can distinguish with
      high Se normal tissues from either benign or neoplastic tissues from breast,
      lung, or prostate lesions. Analyses of fatty acyl chains from ethanolamine
      containing plasmalogens provided a reliable tumor marker that correlated with
      high Se and linearity with metastases spreading. This fact may be useful in
      prognosis of the most frequently observed human cancers.

PMID- 18046594
TI  - Comparison of low fat and low carbohydrate diets on circulating fatty acid
      composition and markers of inflammation.
AB  - Abnormal distribution of plasma fatty acids and increased inflammation are
      prominent features of metabolic syndrome. We tested whether these components of
      metabolic syndrome, like dyslipidemia and glycemia, are responsive to
      carbohydrate restriction. Overweight men and women with atherogenic dyslipidemia
      consumed ad libitum diets very low in carbohydrate (VLCKD) (1504
      kcal:%CHO:fat:protein = 12:59:28) or low in fat (LFD) (1478 kcal:%CHO:fat:protein
      = 56:24:20) for 12 weeks. In comparison to the LFD, the VLCKD resulted in an
      increased proportion of serum total n-6 PUFA, mainly attributed to a marked
      increase in arachidonate (20:4n-6), while its biosynthetic metabolic
      intermediates were decreased. The n-6/n-3 and arachidonic/eicosapentaenoic acid
      ratio also increased sharply. Total saturated fatty acids and 16:1n-7 were
      consistently decreased following the VLCKD. Both diets significantly decreased
      the concentration of several serum inflammatory markers, but there was an overall
      greater anti-inflammatory effect associated with the VLCKD, as evidenced by
      greater decreases in TNF-alpha, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1.
      Increased 20:4n-6 and the ratios of 20:4n-6/20:5n-3 and n-6/n-3 are commonly
      viewed as pro-inflammatory, but unexpectedly were consistently inversely
      associated with responses in inflammatory proteins. In summary, a very low
      carbohydrate diet resulted in profound alterations in fatty acid composition and
      reduced inflammation compared to a low fat diet.

PMID- 18046595
TI  - The lengthening of a giant protein: when, how, and why?
AB  - Subcommissural organ (SCO)-spondin is a giant glycoprotein of more than 5000
      amino acids found in Vertebrata, expressed in the central nervous system and
      constitutive of Reissner's fiber. For the first time, in situ hybridization
      performed on zebrafish (Danio rerio) embryos shows that the gene encoding this
      protein is expressed transitionally in the floor plate, the ventral midline of
      the neural tube, and later in the diencephalic third ventricle roof, the SCO. The
      modular organization of the protein in Echinodermata (Strongylocentrotus
      purpuratus), Urochordata (Ciona savignyi and C. intestinalis), and Vertebrata
      (Teleostei, Amphibia, Aves and Mammalia) is also described. As the thrombospondin
      type 1 repeat motifs represent an increasingly large part of the protein during
      Deuterostomia evolution, the duplication mechanisms leading to this complex
      organization are examined. The functional significance of the particularly well
      preserved arrangement of the series of SCO-spondin repeat motifs and
      thombospondin type 1 repeats is discussed.

PMID- 18046596
TI  - Relation of left ventricular hypertrophy to microalbuminuria and C-reactive
      protein in children and adolescents with essential hypertension.
AB  - Microalbuminuria (MA) and C-reactive protein (CRP) levels are predictors of
      increased risk for left ventricular hypertrophy (LVH). Whether the strength of
      association between CRP and LVH is comparable to that of MA in hypertensive
      children is unknown. CRP and MA were measured in 64 children and adolescents with
      essential hypertension (HTN). In the entire population, CRP and MA showed
      positive relations with body mass index (BMI) (r = 0.30, p = 0.04 and r = 0.32, p
      = 0.04, respectively), systolic blood pressure (SBP) (r = 0.63, p = 0.03 and r =
      0.58, p = 0.03, respectively), and LVH (r = 0.86, p < 0.001 and r = 0.81, p <
      0.001, respectively). Patients with LVH (n = 23) had significantly higher BMI (p
      = 0.32), increased SBP (p = 0.031), and higher levels of CRP (p < 0.001) and MA
      (p < 0.001) compared with those without LVH. Multiple linear regression analysis
      demonstrated that CRP (r = 2.11, p < 0.001), MA (r = 1.94, p < 0.003), BMI (r =
      0.53, p = 0.02), and SBP (r = 0.48, p = 0.04) were significantly associated with
      LVH. By analysis of covariance, CRP and MA were significantly different between
      patients who had LVH and those without LVH after adjustment for age, gender, BMI,
      SBP, SBP index, and diastolic blood pressure (p < 0.001 for the two markers). In
      conclusion, the strength of association between LVH and CRP is comparable to that
      of MA in children and adolescents with essential HTN.

PMID- 18046597
TI  - Cord blood lipid profile in a population of Iranian term newborns.
AB  - Premature coronary artery disease (CAD) and its risk factors are highly prevalent
      in Iran. It is well documented that atherosclerosis starts in childhood and there
      is evidence that this association with adult levels may originate at birth, so
      assessment of serum lipid levels in neonates might be of importance. In this
      study we aimed to measure serum lipoprotein and apolipoprotein levels in a
      representative sample of Iranian newborns. Cord blood lipid profile,
      apolipoprotein A, apolipoprotein B, and lipoprotein a (LPa) were analyzed in 378
      full-term, Iranian newborns. The mean values of total cholesterol (TC), low
      density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C),
      apolipoprotein A, apolipoprotein B, and Lpa in girls were 81.4 +/- 28.3, 35.9 +/-
      22.4, 31.1 +/- 9.9, 87.9 +/- 20.2, 34.2 +/- 18.2, and 21.0 +/- 2.8 mg/dL,
      respectively; these values in boys were 75.2 +/- 21.1, 32.1 +/- 16.3, 28.8 +/-
      8.7, 84.3 +/- 16.0, 32.6 +/- 14.2, and 19.5 +/- 2.7 mg/dL, respectively. Median
      values of triglycerides (TGs) in boys and girls were 61 and 62 mg/dL,
      respectively. Female neonates had significantly higher concentrations of TC and
      HDL-C than males (81.4 +/- 28.3 vs. 75.2 +/- 21.1, p = 0.02, and 31.18 +/- 9.97
      vs. 28.8 +/- 8.7, p = 0.02, respectively). Other biochemical factors were not
      significantly different between genders. The mean and median concentrations of
      LPa were 20.3 and 18.7 mg/dL, respectively, which are almost five times higher
      than those reported in some other studies. The TG concentration was 1.5-2 times
      higher than those previously reported. Our findings indicate that serum
      concentrations of LPa and TG in Iranian neonates are higher than those in
      previous studies; this disorder, which is likely placing Iranians at increased
      risk for future CADs, needs to be assessed in longitudinal studies.

PMID- 18046598
TI  - A simple and feasible technique for repair of anomalous origin of the left
      pulmonary artery from the ascending aorta.
AB  - Anomalous origin of the left pulmonary artery from the ascending aorta is a rare
      congenital cardiac malformation and the direct reimplantation technique has been
      the strategy of choice, although postoperative restenosis across the anastomosis
      site is frequently observed. In the described case, a simple and feasible
      technique was used with satisfactory results at 20-month follow-up.

PMID- 18046599
TI  - Percutaneous stent placement in children weighing less than 10 kilograms.
AB  - The objectives of this study were to evaluate the safety, efficacy, and outcomes
      of palliative percutaneous stent placement in infants with congenital heart
      disease (CHD). There is interest in improving outcomes of infants with CHD
      through interventional/surgical collaboration. Small, high-risk patients may
      benefit from delayed open operations, and endovascular stents may provide a means
      to defer surgery to more advantageous times in select infants. Patients weighing
      < or =10 kg in whom stent placement was attempted during 2003-2006 were
      identified. Diagnoses, indications, angiographic and hemodynamic data,
      complications, and outcomes were reviewed. Seventeen stents were successfully
      placed in 15 patients. The mean age was 10.21 months; the mean weight was 6.08
      kg. Indications were branch pulmonary artery stenosis, coarctation, total
      anomalous pulmonary venous return with obstructed venous egress, right ventricle
      pulmonary artery conduit, and shunt stenosis. Premounted Palmaz Genesis and
      Driver Mx stents were used. Average vessel diameter increased from 3.65 to 6.72
      mm (p < 0.001). The pressure gradient fell from 24 to 15 mm Hg (p < 0.01). Two
      stents migrated. One was recaptured and implanted at the target site and one
      implanted away from the target site. None needed surgical intervention. Mean
      follow-up was 270 days. Five patients have had additional surgery; seven patients
      underwent 10 additional stent dilations. There was no procedural-related
      mortality. Five patients (33%) died during the follow-up period, none
      attributable to the stent placement. We conclude that stent placement can be
      successfully accomplished in select, small, high-risk patients. A collaborative
      interventional/surgical paradigm is important to ensure that the risk-benefit
      ratio is properly evaluated during the patient selection.

PMID- 18046600
TI  - Distribution of Paenibacillus larvae spores among adult honey bees (Apis
      mellifera) and the relationship with clinical symptoms of American foulbrood.
AB  - Knowledge of the distribution of Paenibacillus larvae spores, the causative agent
      of American foulbrood (AFB), among individual adult honey bees is crucial for
      determining the appropriate number of adult bees to include in apiary composite
      samples when screening for diseased colonies. To study spore distribution at the
      individual bee level, 500 honey bees were collected from different parts of eight
      clinically diseased colonies and individually analyzed for P. larvae. From the
      brood chamber and from the super, bees were randomly collected and individually
      put in Eppendorf vials. The samples were frozen as soon as possible after
      collection. Concurrently with sampling, each colony was visually inspected for
      clinical symptoms of AFB. The number of clinically diseased cells in the colony
      was visually estimated. All samples were cultured in the laboratory for P.
      larvae. The results demonstrate that the spores are not randomly distributed
      among the bees; some bees have much higher spore loads than others. It is also
      clear that as the proportion of contaminated bees increase, the number of spores
      from each positive bee also increases. The data also demonstrated a relationship
      between the number of clinically diseased cells and the proportion of positive
      bees in individual colonies. This relationship was used to develop a mathematical
      formula for estimating the minimum number of bees in a sample to detect clinical
      disease. The formula takes into account the size of the apiary and the degree of
      certainty with which one aims to discover clinical symptoms. Calculations using
      the formula suggest that adult bee samples at the colony level will detect light
      AFB infections with a high probability. However, the skewed spore distribution of
      the adult bees makes composite sampling at the apiary level more problematic, if
      the aim of the sampling is to locate lightly infected individual colonies within
      apiaries. The results suggest that false-negative culturing results from
      composite samples of adult bees from individual colonies with clinical symptoms
      of AFB are highly improbable. However, if single colonies have light infections
      in large apiaries, the dilution effect from uncontaminated bees from healthy
      colonies on the positive bees from diseased colonies may yield false-negative
      results at the apiary level.

PMID- 18046601
TI  - An examination of governance arrangements at Kisakasaka mangrove reserve in
      Zanzibar.
AB  - This study employs insights largely derived from critical reflections on the
      common pool resources (CPR) theory to examine the current governance arrangements
      in place to manage the mangrove forest at Kisakasaka, in Zanzibar, Tanzania.
      Kisakasaka was used as a site for a community-based management pilot project of
      forest resources in Zanzibar. After some initial success in setting up a local
      management structure and regulating access to the mangrove for mainly charcoal
      production, there are now clear indications that forest conditions have
      deteriorated dramatically with concomitant ongoing resource use problems for
      local villagers who have relied heavily on forest resources as a source of cash
      income. Extra-local factors, such as urban population increases and associated
      market pressures for charcoal, are also conjectured to overlay and interact with
      the institutional problems at Kisakasaka. As a result, over concern about the
      deterioration in the condition of the mangrove forest, the responsible government
      authority decided not to renew the community-based governance arrangements after
      an initial five-year pilot period. While revealing the inadequacies of existing
      governance arrangements and of its relationship to deteriorating forest
      conditions at Kisakasaka, this study concludes by suggesting an approach to more
      fully understand forces driving local resource management and use.

PMID- 18046602
TI  - Support for simulation-based surgical education through American College of
      Surgeons--accredited education institutes.
AB  - The American College of Surgeons (ACS) recently launched a new program to provide
      regional support for simulation-based surgical education through the
      establishment of a consortium of accredited education institutes. The goals of
      the program are to enhance surgical patient safety, support efforts of surgeons
      to meet the requirements for Maintenance of Certification, address the core
      competencies that all surgeons and surgical residents need to achieve and
      demonstrate, and enhance access to contemporary surgical education. The ACS
      accredited institutes will comprehensively address the needs of a broad spectrum
      of learners and advance the science of simulation-based surgical education.
      Accreditation is being offered at two levels--Level I (Comprehensive) and Level
      II (Basic)--based on three standards that focus on the learners served, the
      curricula offered, and the technological support and resources available. Initial
      plans of the consortium of ACS-accredited Education Institutes include
      development and dissemination of innovative curricula, peer review of new
      educational programs and products, sharing of limited educational resources, and
      pursuit of collaborative research and development. This program should be of
      great value in supporting the professional activities of surgeons, surgical
      residents, medical students, and members of the surgical team, and in delivering
      surgical care of the highest quality.

PMID- 18046604
TI  - TIPS can be lifesaving in acute liver failure associated with portal vein and
      inferior vena cava thrombosis in a case of Budd Chiari syndrome due to protein S
      deficiency.

PMID- 18046605
TI  - Molecular characterization of Japanese sillago vitellogenin and changes in its
      expression levels on exposure to 17beta-estradiol and 4-tert-octylphenol.
AB  - We cloned a full-length cDNA encoding vitellogenin (VTG) from a marine teleost,
      the Japanese sillago Sillago japonica. The cloned sillago VTG contained signal
      peptide, lipovitellin heavy chain, phosvitin, lipovitellin light chain, and beta'
      component in the order from the N-terminus. An exposure to 17beta-estradiol
      significantly increased the levels of plasma VTG, but not hepatic VTG mRNA in
      males. Neither plasma VTG nor hepatic VTG mRNA levels were affected by the
      exposure to 4-tert-octylphenol. Hepatic VTG mRNA levels in males increased at 1
      day after intraperitoneal administration of 17beta-estradiol but decreased in the
      subsequent 5 days. However, plasma VTG levels remained high for 5 days after
      administration, suggesting that the accumulation period of plasma VTG is longer
      than that of hepatic VTG mRNA in males. Therefore, VTG mRNA may be a suitable
      indicator of temporal exposure to estrogenic chemicals in the environment,
      whereas plasma VTG is useful to detect consecutive exposure.

PMID- 18046606
TI  - Developmental changes of mechanics measured in the gerbil cochlea.
AB  - This report describes stiffness and best frequency measurements obtained in vitro
      from the basilar membrane of the gerbil cochlea at the onset of hearing, during
      hearing maturation, and after hearing has matured. Our stiffness data constitute
      the first direct experimental evidence of developmental stiffness changes in the
      basal and middle turns. Stiffness changes by a factor of 5.5 in the basal turn
      between postnatal day 11 and adult, and the difference from adult is
      statistically significant for all ages measured up to postnatal day 16. For the
      middle turn, stiffness changes by a factor of 1.6 between postnatal day 11 and
      adult. Whereas for postnatal day 12 and beyond there is no statistically
      significant difference from adult, our data suggest that there may be a
      significant difference of stiffness between day 11 and adult in the middle turn.
      For the basal turn, our motion measurements confirm a passive component to the
      developmental best frequency shift. For the middle turn, changes in best
      frequency are not statistically significant. Best frequency was determined by
      stimulating the tissue at audio frequencies with a glass paddle and measuring
      motion with a computer-based imaging system. Tissue stiffness was measured with a
      piezoelectric-based sensor system. Tissue stiffness changes have previously been
      postulated to contribute to the best frequency shift observed in the cochlear
      base. Incorporating our data into a simple spring-mass resonance model
      demonstrates that our experimentally measured stiffness change can account for
      the change of best frequency. These results suggest that a stiffness change is,
      in fact, a critical component of the best frequency shift observed in the basal
      turn of the gerbil cochlea after the onset of hearing.

PMID- 18046607
TI  - Prevalence of anal cytologic abnormalities in a French referral population: a
      prospective study with special emphasis on HIV, HPV, and smoking.
AB  - PURPOSE: Studying anal cytology to detect intraepithelial neoplasia has been
      demonstrated to be useful in highly selected populations. This study was designed
      to determine the frequency of abnormal smears in a wide sample of patients
      consulting for anorectal symptoms. METHODS: An anal smear was proposed during
      each consultation during a three-month period. RESULTS: A total of 205 patients
      (112 females) were included. After the consultation, visible condylomas were
      detected in 12 (6 percent) of the cases. Two hundred three (99 percent) smears
      were able to be analyzed. No case of high-grade squamous intraepithelial lesion
      was found. Four cases of low-grade squamous intraepithelial lesion were found,
      all in HIV patients with a history of condylomatous lesions. Forty smears were
      interpreted as atypical squamous cells of undetermined significance and 159 were
      normal. The prevalence in this population of low-grade squamous intraepithelial
      lesion was 19 percent (4/21) in HIV seropositive males, and 15 percent (4/26) in
      the case of a past history of condyloma. The factors associated with an abnormal
      smear (low-grade squamous intraepithelial lesion or atypical squamous cells of
      undetermined significance) were a history of anal condylomatous lesions (odd
      ratio, 4.9; range, 2.1-11.5), HIV seropositivity (odd ratio, 4; range, 1.6-9.9),
      and smoking (odd ratio, 2.1; range, 1.1-11.5). CONCLUSIONS: This work confirms
      that the frequency of low-grade squamous intraepithelial lesion is raised in HIV
      seropositive males and also where there is a history of condyloma, which
      corroborates the necessity for regular monitoring and screening of these patients
      at risk. This study also suggests that the use of tobacco is associated with anal
      cytologic abnormalities.

PMID- 18046608
TI  - Effect of long-term forest fertilization on Scots pine xylem quality and wood
      borer performance.
AB  - We tested whether changes in long-term nutrient availability would affect the
      xylem quality and characteristics of Scots pine trees as a food source for the
      larvae of the xylophagous wood borer Hylotrupes bajulus L. (Cerambycidae). We
      looked for an effect of host plant growth and xylem structural traits on H.
      bajulus larval performance, and looked for delayed effects of long-term forest
      fertilization on xylem chemical quality. In general, larval performance was
      dependent on larval developmental stage. However, the growth of larvae also
      varied with host plant quality (increases in the concentration of nitrogen and
      carbon-based secondary compounds of xylem were correlated with a decrease in the
      larval growth rate). The greater annual growth of trees reduced tracheid length
      and correlated positively with second-instar H. bajulus growth rate. This is
      consistent with the hypothesis that intrinsic growth patterns of host plants
      influence the development of the xylophagous wood borer H. bajulus.

PMID- 18046609
TI  - Compressed voxels for high-resolution phantom simulations in GATE.
AB  - PURPOSE: We report here on a technique to implement high-resolution objects with
      voxels having variable dimensions (compressed) for the reduction of memory and
      central processing unit (CPU) requirements in Monte Carlo simulations. The
      technique, which was implemented in GATE, the GEANT4 application for positron
      emission tomography/single photon emission computed tomography (PET/SPECT)
      imaging simulations, was developed in response to our need for realistic high
      resolution phantoms for dosimetry calculations. PROCEDURES: A compression
      algorithm similar to run-length encoding for one-dimensional data streams, was
      used to fuse together adjacent voxels with identical physical properties. The
      algorithm was verified by conducting dosimetric calculations and imaging
      experiments on compressed and uncompressed phantoms. RESULTS: Depending on the
      initial phantom size and composition, compression ratios of up to 99.9% were
      achieved allowing memory and CPU reductions of up to 85% and 70%, respectively.
      The output of the simulations was consistent with respect to the goals for each
      type of simulation performed (dosimetry and imaging). CONCLUSIONS: The
      implementation of compressed voxels in GATE allows for significant memory and CPU
      reduction and is suitable for dosimetry as well as for imaging experiments.

PMID- 18046610
TI  - Update in women's health 2006-2007.

PMID- 18046611
TI  - Intrahepatic repair of bile duct injuries. A comparative study.
AB  - INTRODUCTION: The frequency of bile duct injuries associated to cholecystectomy
      remains constant (0.3-0.6%). A multidisciplinary approach (endoscopical,
      radiological, and surgical) is necessary to optimize the outcome of the patient.
      Surgery is indicated when complete section of the duct is identified (Strasberg's
      E injuries) requiring a bilioenteric anastomosis as treatment. Nowadays, the most
      frequent technique used for reconstruction is a Roux-en-Y hepatojejunostomy. Long
      term results of reconstruction are related to several technical and anatomic
      factors, but an ischemic duct (with subsequent scarring) plays a mayor role. In
      this paper, we report the results of biliary reconstructions comparing the
      extrahepatic-probably ischemic -- to intrahepatic -- non ischemic -- repairs.
      METHODS: We reviewed the files of patients referred to our hospital (third-level
      teaching hospital) for bile duct repair after iatrogenic injury from 1990 to July
      2006. Injury classification, time lapse since injury, surgical repair technique,
      and long-term follow-up were noted. In all cases, a Roux-en-Y hepatojejunostomy
      was done. Partial resection of segment IV was performed in 136 patients to obtain
      noninflamed, nonscarred, nonischemic biliary ducts with the purpose of reaching
      the confluence and achieving a high-quality bilioenteric anastomosis. An
      anastomosis at the level of the confluence was attempted in 293 patients (in 198
      the confluence was preserved and in 95 it was lost). In the remaining 80
      patients, a low bilioenteric anastomosis was done at the level of the common
      hepatic duct. We compared intrahepatic (198) and extrahepatic (80) repairs.
      RESULTS: A total of 405 cases (88 males, 317 females) were identified, with a
      mean age of 42 years (range 17-75). All of the injuries were classified as
      Strasberg E1, E2, E3, E5 (less frequent); those with E4 classification (separated
      ducts) were excluded. In all cases, the confluence was preserved (N = 293).
      Thirty-two cases were repaired minutes to hours after the injury occurred. The
      remaining 373 patients arrived weeks after the injury. In 198 cases, an
      intrahepatic repair was done, including the 136 in which resection of segments IV
      and V was part of the surgery. In the remaining 80 cases (operated between 1990
      and 1997), an extrahepatic repair was done at the level of the common hepatic
      duct where the surgeon found a healthy duct. Twelve (15%) of the 80 cases with
      extrahepatic anastomosis required a new intervention (surgical or radiological),
      compared to only 8 of the 198 (3%) that had an intrahepatic anastomosis (P =
      0.00062). Good results were obtained in 85% and 97% of the cases with
      extrahepatic anastomosis and intrahepatic anastomosis, respectively. Both groups
      had a reintervention rate of 7% (20/278). CONCLUSIONS: An intrahepatic
      anastomosis requires finding nonscarred, nonischemic ducts, thus allowing a safe
      and high-quality anastomosis with significantly better results when compared to
      the low-level anastomosis group.

PMID- 18046612
TI  - Surgical treatment of primary neuroendocrine tumors of the liver.
AB  - Primary neuroendocrine tumor (NET) of the liver is a very rare neoplasm,
      requiring strict exclusion of possible extrahepatic primary sites for its
      diagnosis. We have analyzed our clinical experience of eight patients with
      hepatic primary NET. From January 1997 to December 2006, eight patients with a
      mean age of 50.4 +/- 9.5 years underwent liver resection for primary hepatic NET.
      Seven patients underwent preoperative liver biopsies, which correctly diagnosed
      NET in four. Of the eight patients, six underwent R0 and two underwent R1
      resection. Diagnosis of hepatic primary NET was confirmed immunohistochemically
      and by the absence of extrahepatic primary sites. All tumors were single lesions,
      of mean size 8.6 +/- 5.7 cm, and all showed positive staining for synaptophysin
      and chromogranin. During a mean follow-up of 34.0 +/- 39.7 months, three patients
      died of multiple liver metastases after tumor recurrence, whereas the other five
      remain alive to date, making the 5-year recurrence rate 40% and the 5-year
      survival rate 56.3%. Univariate analysis showed that Ki67 proliferative index was
      a risk factor for tumor recurrence. In conclusion, although primary hepatic NET
      is very rare, it should be distinguished from other liver neoplasms. The mainstay
      of treatment is curative liver resection.

PMID- 18046614
TI  - Four trace elements contents of water environment of mining subsidence in the
      Huainan diggings, China.
AB  - Mining subsidence pool is the special waters formed by coal mining, located near
      the mine. We understand the impact on these waters of the surrounding coal
      production activities and the electricity plant through research the content and
      characteristics of harmful trace elements in coal contained in these waters. Pb,
      Hg, Se and Cr these four trace elements increase 0.52, 0.78, 0.70 and 0.28%
      respectively in Datong mining subsidence pool from November 2004 to November
      2006; the four elements increase 1.52, 1.23, 1.08 and 1.08% respectively in
      Xie'er mining subsidence pool; the four elements increase 1.01, 1.06, 1.02 and
      0.83% respectively in Pansan mining subsidence pool. The absolute value of Pb,
      Hg, Se and Cr in mining subsidence pool is related with their background value,
      while the increase in their concentration and their environment of mine and
      electricity plant surrounded are closely linked.

PMID- 18046613
TI  - Peptide YY and glucagon-like peptide-1 in morbidly obese patients before and
      after surgically induced weight loss.
AB  - BACKGROUND: Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are cosecreted
      in the same enteroendocrine L-cells of the gut and reported to inhibit food
      intake additively. However, findings in human studies regarding these peptides
      are controversial. The aim of this study was to analyze the relationships between
      fasting PYY, GLP-1, and weight status in morbidly obese patients before and after
      surgically induced weight loss. METHODS: Fasting GLP-1, PYY, glucose, and insulin
      concentrations; blood pressure; and body-mass index (BMI) were determined in 30
      morbidly obese adults (mean BMI 45.8, mean age 40 years) before bariatric surgery
      [Roux-en-Y gastric bypass (RYGB): n = 19; gastric banding (GB): n = 11] and after
      weight loss (mean 50% excess weight loss) in the course of mean 2 years. RESULTS:
      GLP-1 concentrations decreased (mean -20 pg/ml; mean -38%; p = 0.001) and PYY
      concentrations increased (mean +19 pg/ml; mean +19%, p = 0.036) after bariatric
      surgery. The weight loss and changes of GLP-1 were significantly (p < 0.05) more
      pronounced after RYGB as compared to GB, whereas the changes of PYY did not
      differ significantly between the patients who had undergone RYGB or GB.
      CONCLUSIONS: In morbidly obese adults reducing their weight by bariatric surgery,
      fasting PYY levels increased and GLP-1 concentrations decreased independently of
      each other. Therefore, the relationship between PYY and GLP-1 seems more
      complicated than might be anticipated from animal and in vitro studies.

PMID- 18046615
TI  - Determination of aluminum and zinc in Iranian consumed tea.
AB  - To determine aluminum and zinc in Iranian consumed tea, 31 tea samples were
      analysed for Al and Zn concentration of tea leaves and tea infusion. The results
      show that average concentration of Al and Zn in tea leaves was 326 and 50.7 mg.
      Kg(-1) respectively in this regard Nemoneh and Shahrzad show the highest and
      lowest concentration respectively in term of Al, also Debsh and Alkozi follow
      same situation in Zn concentration. Also the solubility of metals in the first
      infusion was significantly (Al, Zn: P < 0.01) higher than the second infusion and
      the solubility in the second infusion was also significantly higher than the
      third infusion (Al: P < 0.01; Zn: P < 0.05). Al leachate in the first infusion (2
      min) for Mosama and Seilan tea was highest and lowest respectively. Also in the
      second and third infusion (5 and 10 min) Golkis and Nemoneh tea show the highest
      and lowest figures respectively. On the other hand, data from Zn transfer in tea
      infusion in the first infusion show that Mosama and Ahmad Atry tea have the
      highest and lowest leachate percentage respectively, while in the second and
      third infusion Mosama and Golkis tea follow the same situation. Calculation of
      percentage 'available' Al and Zn to the human system showed that 1 l of tea can
      provide 37.2% of the daily dietary intake of Al, the percentage 'available' for
      absorption in the intestine is only 1.78% for overall mean Al concentration. Also
      daily dietary intake of Zn was 2.13% while percentage available for absorption in
      the intestine was 0.72%.

PMID- 18046617
TI  - Locating air quality monitoring station using wind impact area diagram.
AB  - In this study a new methodology is suggested to approximate the impact area
      downwind of an air pollution source, where air quality monitoring can be carried
      out to capture the maximum pollutant concentration. Hourly wind speed for a given
      month is grouped in to different wind speed ranges and the distance of pollutant
      travel is approximated from the average wind speed of that wind speed range.
      Since change in wind direction causes the impact distance to rotate, its rotation
      is approximated by the SD of wind direction change. Using this approach, area or
      region down wind of a source is determined and plotted. The pattern of monthly
      change of wind is better represented by the new type of diagram as compared to
      the wind rose diagram.

PMID- 18046616
TI  - Determination of heavy metal levels in water, sediment and tissues of tench
      (Tinca tinca L., 1758) from Beysehir Lake (Turkey).
AB  - In the present study, some heavy metals (Cu, Fe, Zn and Mn) were seasonally
      determined in water, sediment and some tissues of fish Tinca tinca from Beysehir
      Lake, which is an important bird nesting and visiting area, a water source for
      irrigation and drinking. In the water, Fe has the highest concentrations among
      the studied metals. Generally, the metal concentrations increased in the hottest
      period decreased in warm seasons. Results for levels in water were compared with
      national and international water quality guidelines, as well as literature data
      reported for the lakes. Fe was the highest in sediment samples, also Cu and Zn
      were the highest in spring, while Fe and Mn were in autumn. Among the heavy
      metals studied, Cu and Mn were below the detection limits in some tissues.
      Generally, higher concentrations of the tested metals were found in the summer
      and winter, compared with those during the autumn and spring seasons. High levels
      of heavy metals were found in liver of T. tinca, while low levels in muscle
      samples. Metal concentrations in the muscle of examined fish were within the
      safety permissible levels for human consumption. The present study shows that
      precautions need to be taken in order to prevent further heavy metal pollution.

PMID- 18046618
TI  - Ertapenem-induced acute pancreatitis in a surgical elderly patient.
AB  - Case summary A 78-year old man was given, after surgery, 1 g ertapenem every 24 h
      intravenously. His clinical evolution was favorable and on day 8 ertapenem was
      discontinued and the patient was put on a semi-solid diet. On day 9, abdominal
      distension was seen accompanied by epigastric pain. The laboratory tests on day 8
      showed an altered pancreatic profile: amylase = 1823 U/l (normal value: 0-100);
      lipase = 8045 U/l (normal value: 0-60); C-reactive protein (CRP) = 16.09 mg/dl
      (normal value: 0-0.5). Full Blood Count (FBC) showed leukocytosis with an
      increase in neutrophils and eosinophils. The prior pancreatic parameters were
      normal without leukocytosis. The evolution of clinical symptoms after
      discontinuing ertapenem was rapid. Between days 11 and 16, the laboratory
      parameters returned to normal values; the eosinophilia persisted longer,
      decreasing between days 14 and 16. Conclusions clinicians should include
      monitoring the development of acute pancreatitis in the safety parameters in
      patients undergoing treatment with this carbapenem.

PMID- 18046620
TI  - Change of body weight and lifestyle of persons at risk for diabetes after
      screening and counselling in pharmacies.
AB  - OBJECTIVE: To investigate the effects of pharmacy based counselling on changes in
      lifestyle and body weight. METHODS: Three months after screening a stratified
      sample of 3,800 randomly chosen overweight persons were addressed with
      questionnaires. Half a year and 1 year later the assessment was repeated.
      Standard counselling (SC; non-specific recommendations towards lifestyle),
      intensive counselling (IC; additional advice to reduce body weight) and
      counselling for persons at high risk for type 2 diabetes (HRC; recommendation to
      contact a physician) were compared. RESULTS: All counselling groups (SC; n = 557,
      IC; n = 568, HRC; n = 245) showed significant weight loss three months after
      screening (0.6-1.9 kg). A further weight reduction was observed at 1 year follow
      up (1.1-2.4 kg). The HRC group showed a higher percentage of weight loss than the
      IC or SC group after 3 months (-2.25% vs. -1.20% and -0.67%; P < 0.001) and at 1
      year of follow-up (-2.74% vs. -1.54% and -1.29%; P < 0.01). Lifestyle changes in
      physical activity and/or nutrition were reported by 81.2% in the HRC group, 74.1%
      in the IC group and 67.0% in the SC group. CONCLUSION: Immediate counselling in
      community pharmacies after screening for type 2 diabetes can result in
      significant lifestyle changes and weight loss in overweight individuals.

PMID- 18046621
TI  - Feedback to doctors about prescribing errors in the hospital setting.

PMID- 18046622
TI  - Immunohistochemical and immunocytochemical detection of SchS34 antigen in
      Stachybotrys chartarum spores and spore impacted mouse lungs.
AB  - The purpose of this study was to evaluate the distribution of a 34 kD antigen
      isolated from S. chartarum sensu lato in spores and in the mouse lung 48 h after
      intra-tracheal instillation of spores by immuno-histochemistry. This antigen was
      localized in spore walls, primarily in the outer and inner wall layers and on the
      external wall surfaces with modest labelling observed in cytoplasm. Immuno
      histochemistry revealed that in spore impacted mouse lung, antigen was again
      observed in spore walls, along the outside surface of the outer wall and in the
      intercellular space surrounding spores. In lung granulomas the labelled antigen
      formed a diffusate, some 2-3x the size of the long axis of spores, with highest
      concentrations nearest to spores. Collectively, these observations indicated that
      this protein not only displayed a high degree of specificity with respect to its
      location in spores and wall fragments, but also that it slowly diffuses into
      surrounding lungs.

PMID- 18046623
TI  - Malassezia spp. in acoustic meatus of bats (Molossus molossus) of the Amazon
      Region, Brazil.
AB  - The yeasts of the Malassezia genus are opportunistic microorganisms and can cause
      human and animal infections. They are commonly isolated from the skin and
      auricular canal of mammalians, mainly dogs and cats. The present study was aimed
      to isolate Malassezia spp. from the acoustic meatus of bats (Molossus molossus)
      in the Montenegro region, "Rondonia", Brazil. From a total of 30 bats studied
      Malassezia spp. were isolated in 24 (80%) animals, the breakdown by species being
      as follows (one Malassezia sp. per bat, N = 24): 15 (62.5%) M. pachydermatis, 5
      (20.8%) M. furfur, 3 (12.5%) M. globosa and 1 (4.2%) M. sympodialis. This study
      establishes a new host and anatomic place for Malassezia spp., as it presents the
      first report ever of the isolation of this genus of yeasts in the acoustic meatus
      of bats.

PMID- 18046624
TI  - An investigation on the polymorphisms of two DNA repair genes and susceptibility
      to ESCC and GCA of high-incidence region in northern China.
AB  - AIM: To investigate the possible association of three SNPs, XRCC2 C41657T, XRCC2
      G4234C and XRCC3 A17893G with susceptibility to esophageal squamous cell
      carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in a population of
      northern China. METHODS: XRCC2 C41657T, XRCC2 G4234C and XRCC3 A17893G SNP were
      genotyped by polymerase-chain reaction (PCR)-restriction fragment length
      polymorphism (RFLP) analysis in 583 cancer patients (329 ESCC and 254 GCA) and
      614 healthy controls. RESULTS: The genotype distribution of the XRCC2 C41657T in
      ESCC and GCA patients were significantly different from that in healthy controls
      (P values = 0.04 and 0.04 respectively). And a significant difference was found
      in the allele distribution of GCA patients from that in controls (P = 0.01). The
      XRCC2 C41657T polymorphism was associated with a modest enhancement in ESCC risk
      and GCA risk: OR for C/T genotype was 1.38 (1.01-1.89) in GCA risk and for T/T
      genotype was 2.24 (1.10-4.57) in ESCC risk. When stratified for age, smoking
      status and family history of UGIC, the C/T genotype showed a modest significant
      trend on the risk of GCA patients in the groups of age < or =50 years and non
      smokers, the adjusted OR were 2.84 (1.21-6.66) and 1.62 (1.06-2.49). The T/T
      genotype significantly increased the susceptibility of GCA patients in negative
      family history of UGIC (3.04, 1.02-8.32) and to ESCC patients in the group of age
      >50 years (3.03, 1.31-6.98), Negative family of UGIC (3.03, 1.12-7.07) and
      smokers (2.64, 1.02-6.83). The genotype and allele distribution of XRCC2 G4234C
      and XRCC3 A17893G in ESCC and GCA patients were not significantly different from
      that in healthy controls (all P values were above 0.05). CONCLUSION: In this
      study, we found that the C41657T polymorphism of XRCC2 genes might modify the
      risk of ESCC and GCA development.

PMID- 18046625
TI  - Frequency of cystathionine beta-synthase 844INS68 polymorphism in Southern Iran.
AB  - Iranian population with an Indo-European origin is one of the oldest populations
      in the world. Historical evidence suggests the close similarity in the origin of
      Iranian, European and north Indian population. However, there are few
      anthropological and genetic evidences on this subject. This study, which is the
      first report from Iran, was performed to investigate the genetic origin of
      Iranian population using a polymorphism in Cystathionine beta synthase (CBS) gene
      known as 844INS68bp in this respect, genomic DNA was extracted from the whole
      blood of 480 healthy normal blood donors referred to Fars Blood Transfusion
      Center, using a salting out method. The fragment containing 844INS68bp was
      amplified, the normal fragment was 174 bp and the fragment containing the
      insertion was 242 bp in length. Results indicated that 418 (87.08%) out of 480
      individuals had a normal (N/N) genotype, 59 (12.29%) individuals were
      heterozygote (N/I) and 3 (0.63%) had homozygote a mutated genotype (I/I). The
      total frequency of 844INS68bp allele was found 6.8% which is similar to with the
      reported in White Caucasians. Comparison of the genotype of this study with the
      polymorphism in other populations revealed that Southern Iranian population has a
      great similarity with other Caucasians populations' especially South Italy and
      North America while differed from East Asian and African populations. These
      results are in agreement with the result of other studied polymorphisms.
      Therefore, despite the great admixture of Iranian population with the neighboring
      non-Caucasian populations during the time, Iranian population still share a
      genetic background with other Caucasian populations.

PMID- 18046626
TI  - Mitochondrial nad2 gene is co-transcripted with CMS-associated orfB gene in
      cytoplasmic male-sterile stem mustard (Brassica juncea).
AB  - The transcriptional patterns of mitochondrial respiratory related genes were
      investigated in cytoplasmic male-sterile and fertile maintainer lines of stem
      mustard, Brassica juncea. There were numerous differences in nad2 (subunit 2 of
      NADH dehydrogenase) between stem mustard CMS and its maintainer line. One novel
      open reading frame, hereafter named orfB gene, was located at the downstream of
      mitochondrial nad2 gene in the CMS. The novel orfB gene had high similarity with
      YMF19 family protein, orfB in Raphanus sativus, Helianthus annuus, Nicotiana
      tabacum and Beta vulgaris, orfB-CMS in Daucus carota, atp8 gene in Arabidopsis
      thaliana, 5' flanking of orf224 in B. napus (nap CMS) and 5' flanking of orf220
      gene in CMS Brassica juncea. Three copies probed by specific fragment (amplified
      by primers of nad2F and nad2R from CMS) were found in the CMS line following
      Southern blotting digested with HindIII, but only a single copy in its maintainer
      line. Meanwhile, two transcripts were shown in the CMS line following Northern
      blotting while only one transcript was detected in the maintainer line, which
      were probed by specific fragment (amplified by primers of nad2F and nad2R from
      CMS). Meanwhile, the expression of nad2 gene was reduced in CMS bud compared to
      that in its maintainer line. We thus suggested that nad2 gene may be co
      transcripted with CMS-associated orfB gene in the CMS. In addition, the specific
      fragment that was amplified by primers of nad2F and nad2R just spanned partial
      sequences of nad2 gene and orfB gene. Such alterations in the nad2 gene would
      impact the activity of NADH dehydrogenase, and subsequently signaling, inducing
      the expression of nuclear genes involved in male sterility in this type of
      cytoplasmic male sterility.

PMID- 18046627
TI  - Sequence analysis and expression of a cDNA clone encoding tropomysin in
      Sinonovacula constricta.
AB  - Shellfish can cause severe anaphylactic reactions. Tropomyosin has been assumed
      partly responsible for the cross-reactivity among shellfish and other
      invertebrates. In this study, cDNA of Sinonovacula constricta was amplified by RT
      PCR and 3'-RACE from total RNA. The obtained tropomyosin cDNA included an open
      reading frame coding for 284 amino acids. The deduced amino acid sequence of the
      corresponding protein shared high identity with other allergenic tropomyosins.
      Expression of the recombinant tropomyosin was carried out in Escherichia coli
      BL21(DE3) using vector PET28a and the purification of the recombinant protein was
      performed via affinity chromatography. IgE reactivity of recombinant tropomyosin
      was investigated by immunoblot and the sensized precentage was 36% which
      indicated that tropomyosin was the minor allergens in S. constricta. Moreover,
      the character of the purified protein was analyzed by MALDI-TOF-MS.

PMID- 18046628
TI  - East meets West: cross-cultural perspective in end-of-life decision making from
      Indian and German viewpoints.
AB  - Culture creates the context within which individuals experience life and
      comprehend moral meaning of illness, suffering and death. The ways the patient,
      family and the physician communicate and make decisions in the end-of-life care
      are profoundly influenced by culture. What is considered as right or wrong in the
      healthcare setting may depend on the socio-cultural context. The present article
      is intended to delve into the cross-cultural perspectives in ethical decision
      making in the end-of-life scenario. We attempt to address the dynamics of the
      roles of patient, family and physician therein across two countries from East and
      West, namely, India and Germany. In India, where illness is more a shared family
      affair than an individual incident, a physician is likely to respect the family's
      wishes and may withhold the [Symbol: see text]naked truth' about the diagnosis of
      a fatal disease to the patient. In Germany, a physician is legally required to
      inform the patient about the disease. In India, advance directive being virtually
      non-existent, the family acts as the locus of the decision-making process, taking
      into account the economic cost of available medical care. In Germany, advance
      directive is regarded as mandatory and healthcare is covered by insurance. Family
      and the physician appear to play larger roles in ethical decision making for
      patients in India than for those in Germany, who place greater emphasis on
      autonomy of the individual patient. Our study explicates how culture matters in
      ethical decision-making and why the bioethical discourse is necessary in the
      concrete realities of the socio-cultural context. To explore the possibility of
      finding a common ground of morality across different cultures while acknowledging
      and respecting cultural diversity, thus remains a formidable challenge for the
      bioethicists.

PMID- 18046630
TI  - New stimuli-responsive polymers derived from morpholine and pyrrolidine.
AB  - The preparation of three new ionizable monomers: N-ethyl morpholine metacrylate
      (EMM), N-ethyl morpholine methacrylamide (EMA) and N-ethyl pyrrolidine
      metacrylamide (EPA) and their respective homopolymers poly-EMM, poly-EMA and poly
      EPA prepared by radical polymerization in solution, is described. The systems
      have been characterized by NMR and FTIR spectroscopic techniques, determined
      their glass transition temperatures by DSC and their respective pKs. Moreover,
      crosslinked samples were prepared by bulk polymerization using N,N-methylene
      bisacrylamide (BAam) and the trifunctional 1,3,5-triacryloylhexa-hydro-1,3,5
      triazine (135-T) as crosslinkers. The studies of swelling kinetics were carried
      out in different pH buffer solutions (2, 7.4 and 10) in a thermostatic bath at 37
      degrees C showing hydration degrees that go from 2,600% to about 200% depending
      on the pH and on the crosslinker used. The systems seem to be suitable for the
      preparation of smart hydrogels for drug delivery and Tissue Engineering.

PMID- 18046629
TI  - Hereditary diffuse gastric cancer: association with lobular breast cancer.
AB  - Hereditary diffuse gastric cancer (HDGC) has been shown to be caused by germline
      mutations in the gene CDH1 located at 16q22.1, which encodes the cell-cell
      adhesion molecule, E-cadherin. Not only does loss of expression of E-cadherin
      account for the morphologic differences between intestinal and diffuse gastric
      cancer (DGC) variants, but it also appears to lead to distinct cellular features
      which appear to be common amongst related cancers that have been seen in the
      syndrome. As in most hereditary cancer syndromes, multiple organ sites may be
      commonly affected by cancer, in HDGC, lobular carcinoma of the breast (LBC) and
      possibly other organ sites have been shown to be associated with the familial
      cancer syndrome. Given the complexity of HDGC, not only with regard to the
      management of the DGC risk, but also with regard to the risk for other related
      cancers, such as LBC, a multi-disciplinary approach is needed for the management
      of individuals with known CDH1 mutations.

PMID- 18046631
TI  - A tertiary amino-containing polymethacrylate polymer protects mucus-covered
      intestinal epithelial monolayers against pathogenic challenge.
AB  - PURPOSE: We examined the cytoprotective influences of the mucoadhesive polymer,
      poly(DMAEMA), on human mucus-producing intestinal epithelial monolayers against
      two bacterial exotoxins and S. typhimurium. Direct anti-bacterial effects were
      also assessed against S. typhimurium. METHODS: In the presence and absence of
      mucus, untreated or poly(DMAEMA)-exposed monolayers were challenged with S.
      typhimurium or supernatants containing either cholera (CTx) or C. difficile
      toxins. Assays included LDH, cytokine secretion, cyclic AMP (cAMP) and microscopy
      to visualise bacterial adherence by monolayers. The minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC) of poly(DMAEMA)
      against S. typhimurium were established, along with a time-kill study. RESULTS:
      CTx and C. difficile toxin induced LDH release from E12 monolayers. CTx also
      elevated intracellular epithelial cAMP, while S. typhimurium induced basolateral
      IL-8 secretion. Pre-treatment of E12 monolayers with poly(DMAEMA) reduced these
      effects, but only in the presence of mucus. The polymer co-localised with S.
      typhimurium in mucus and reduced bacteria-epithelia association. Poly(DMAEMA) was
      directly bactericidal against S. typhimurium at 1 mg/ml within 30 min.
      CONCLUSIONS: Poly(DMAEMA) may have potential as a non-absorbed polymer
      therapeutic against infection. These effects were mediated by a combination of
      physical interaction with mucus and by direct bacterial killing.

PMID- 18046632
TI  - Anomalous particle size shift during post-milling storage.
AB  - PURPOSE: To investigate the anomalous phenomenon of particle size shift during
      post-milling storage. MATERIALS AND METHODS: Crystallised and ball-milled adipic
      acid were stored under different humidity conditions. Analyses were carried out
      to characterise changes in particle size distribution (laser diffraction),
      morphology (SEM), bulk flow properties (annular shear tester), surface adhesion
      forces (AFM) and crystallinity (PXRD and DVS). RESULTS: It was observed that the
      particle size distribution of milled adipic acid can shift to finer fractions,
      remain unchanged, or even shift to coarser fractions depending on storage
      conditions. SEM analysis showed that milled adipic acid is composed of
      agglomerates, which can undergo de-aggregation or further agglomeration via re
      crystallisation. Empirical analysis ruled out the effects of electrostatic
      charges on the particle size shift. In addition, an improvement in powder flow in
      terms of bulk tensile strength was seen for milled adipic acid stored under high
      relative humidity but not under low humidity. CONCLUSIONS: Storage of milled
      adipic acid below the critical relative humidity led to localised disintegration
      from the agglomerate surface and particle size reduction, which was not
      influenced by moisture sorption or loss. This evidence supports that "stress
      relaxation" mechanism behind particle breakage of post-milled particles.
      Appropriate storage conditions are important in maintaining the stability of
      milled powders.

PMID- 18046633
TI  - Steady state and time-resolved fluorescence studies of a hemagglutinin from
      Moringa oleifera.
AB  - The saccharide binding and conformational characterization of a hemagglutinin, a
      low molecular weight protein from the seeds of Moringa oleifera was studied using
      steady state and time resolved fluorescence. The lectin binds sugars LacNAc (K
      (a) = 1380 M(-1)) and fructose (K (a) = 975 M(-1)), as determined by the
      fluorescence spectroscopy. It has a single tryptophan per monomer which is
      exposed on the surface and is in a strong electropositive environment as revealed
      by quenching with iodide. Quenching of the fluorescence by acrylamide involved
      both static (K (s) = 0.216 M(-1)) and collisional (K (sv) = 8.19 M(-1))
      components. The native protein showed two different lifetimes, tau (1) (1.6 ns)
      and tau (2) (4.36 ns) which decrease and get converted into a single one, (2.21
      ns) after quenching with 0.15 M acrylamide. The bimolecular quenching constant, k
      ( q ) was 7.55 x 10(11) M(-1) s(-1). ANS binding studies showed that the native
      protein has exposed hydrophobic patches which get further exposed at extreme
      acidic or alkaline pH. However, they get buried in the interior of the protein in
      presence of 1 M GdnHCl or urea.

PMID- 18046634
TI  - Association of alcohol abuse and injection drug use with immunologic and
      virologic responses to HAART in HIV-positive patients from urban community health
      clinics.
AB  - The purpose of this study is to examine the association of alcohol abuse and
      injection drug use (IDU) with the immunologic and virologic responses to highly
      active antiretroviral treatment (HAART) in urban community health clinics. The
      medical records of 293 HIV-infected adult patients who visited either of two
      urban health clinics in New Haven, Connecticut, from June 2003 to December 2004
      were retrospectively reviewed. Changes in mean CD4 lymphocyte counts and
      undetectable viral loads were compared before and after the initiation of HAART
      for patients categorized into one of four substance abuse groups: history of
      neither alcohol abuse nor IDU, alcohol abuse only, IDU only, or both. Unadjusted
      mean improvements in CD4 count for the four groups were 136, 97, 20, and 27,
      respectively. In a linear regression model adjusted for age, gender, and baseline
      CD4 count, history of IDU only (P = 0.037) and a combination of alcohol abuse and
      IDU (P = 0.038) were associated with a lesser increase in CD4 count after HAART
      compared with those with neither alcohol nor IDU. No significant associations
      were found between substance abuse history and changes in detectable viral load.
      Our results show that many patients at urban health clinics have a history of
      either injection drug use or alcohol abuse, and that injection drug use is
      negatively associated with the immunologic response to HAART in urban HIV
      infected individuals. This study highlights the importance for clinicians of
      understanding the negative associations of substance abuse with the treatment
      response of HIV-infected patients at urban health centers.

PMID- 18046635
TI  - A modeling comparison of projection neuron- and neuromodulator-elicited
      oscillations in a central pattern generating network.
AB  - Many central pattern generating networks are influenced by synaptic input from
      modulatory projection neurons. The network response to a projection neuron is
      sometimes mimicked by bath applying the neuronally-released modulator, despite
      the absence of network interactions with the projection neuron. One interesting
      example occurs in the crab stomatogastric ganglion (STG), where bath applying the
      neuropeptide pyrokinin (PK) elicits a gastric mill rhythm which is similar to
      that elicited by the projection neuron modulatory commissural neuron 1 (MCN1),
      despite the absence of PK in MCN1 and the fact that MCN1 is not active during the
      PK-elicited rhythm. MCN1 terminals have fast and slow synaptic actions on the
      gastric mill network and are presynaptically inhibited by this network in the
      STG. These local connections are inactive in the PK-elicited rhythm, and the
      mechanism underlying this rhythm is unknown. We use mathematical and
      biophysically-realistic modeling to propose potential mechanisms by which PK can
      elicit a gastric mill rhythm that is similar to the MCN1-elicited rhythm. We
      analyze slow-wave network oscillations using simplified mathematical models and,
      in parallel, develop biophysically-realistic models that account for fast, action
      potential-driven oscillations and some spatial structure of the network neurons.
      Our results illustrate how the actions of bath-applied neuromodulators can mimic
      those of descending projection neurons through mathematically similar but
      physiologically distinct mechanisms.

PMID- 18046637
TI  - Emotion work in the public performances of male-to-female transsexuals.
AB  - Much research has shown that entering the public sphere is emotionally taxing yet
      key to male-to-female transsexuals' status passage. Yet, little is known about
      how transsexuals actively manage their emotions during this important
      transitional phase. Taking a dramaturgical approach to emotions, we explored how
      some male-to-female transsexuals managed their emotions in ways that helped
      generate self-confidence and commitment to their paths. Interviewees engaged in
      three primary forms of emotion work: (1) preparatory emotion work mitigated
      anxiety and bolstered confidence, which motivated them to enter public arenas as
      women; (2) in situ emotion work transformed negative emotions as they arose when
      performing womanhood in public; and (3) retrospective emotion work reinterpreted
      past public performances to neutralize negative and accentuate positive emotions.

PMID- 18046636
TI  - Characterization of a membrane protein (VP001L) from infectious spleen and kidney
      necrosis virus (ISKNV).
AB  - Infectious spleen and kidney necrosis virus (ISKNV) is the type species of
      megalocytivirus, Iridoviridae. A novel membrane protein corresponding to the
      first open reading frame (ORF001L) of ISKNV genome was identified. This 378
      residue protein, termed the VP001L protein, has a high content of hydrophobic
      sequences and contains 10-11 putative transmembrane domains, indicating it may be
      a membrane protein. The VP001L mRNA start site was extended 433 bp upstream of
      the start codon and the temporal analysis showed that the VP001L gene was first
      transcribed at 8 h post-infection (h.p.i.). VP001L protein was detected on the
      plasma membrane of ISKNV infected cells by immunofluresence. In order to further
      investigate different transmembrane domains' influence on subcellular
      localization of VP001L, series of truncated or deleted mutants were constructed
      with GFP at the C terminus. The transfection results indicated that the second
      putative transmembrane domain played a determinative role in VP001L's membrane
      localization and the translocation of the first and third transmembrane domains
      depended on their interactions with the second one. Therefore, this novel VP001L
      protein is considered to serve as a model for analyzing the topology and roles of
      different hydrophobic regions in multi-transmembrane proteins.

PMID- 18046638
TI  - The sexual self-consciousness scale: psychometric properties.
AB  - An investigation of the Sexual Self-Consciousness Scale (SSCS) is reported that
      aims to measure individual variability with regard to the construct of self
      consciousness as experienced in sexual situations. The construct relates to the
      attentional-capacity model of sexual arousal. Sexual self-consciousness may
      constitute a vulnerability factor for the development of sexual dysfunction. In
      the present study, men and women with sexual dysfunction and healthy control
      participants were investigated (N = 282). Principal component analysis and
      multitrait scaling analysis showed that a two-component, oblimin-rotated solution
      based on 12 items and explaining 53.7% of the total variance could be well
      interpreted. The Sexual Embarrassment subscale (Cronbach's alpha = .84), the
      Sexual Self-Focus subscale (alpha = .79), and the full scale (alpha = .85) were
      found to have satisfactory to good internal consistency. Test-retest reliability
      was satisfactory for the Sexual Embarrassment subscale (r = .84), the Sexual Self
      Focus subscale (r = .79), and total score (r = .83). An effect of sex was found
      on the Sexual Embarrassment subscale, with female participants scoring higher
      than male participants. Compared with sexually functional participants, sexually
      dysfunctional participants scored higher on the Sexual Embarrassment and Sexual
      Self-Focus subscales. Convergent and divergent construct validity was
      investigated by comparing the associations of SSCS subscales with general self
      consciousness and psychological distress scales. The pattern of correlations was
      interpreted as providing support for the instrument's construct validity. In
      conclusion, the SSCS was found to have satisfactory reliability and validity
      characteristics, and is expected to contribute to the field of sex research and
      clinical sexology.

PMID- 18046640
TI  - Are children with anxiety disorders privately referred to a university clinic
      like those referred from the public mental health system?
AB  - Compared two groups of children with anxiety disorders served at a single mental
      health clinic whose referral source differed: private referrals (i.e.,
      parent/legal guardian initiated) and public referrals (e.g., via state contracts-
      Departments of Health and Education, juvenile justice system). Comparisons were
      made across three domains of variables: (a) symptoms/diagnoses, (b) functioning,
      and (c) environments. Few symptom differences emerged. However, large differences
      were evident for contextual variables like family income and life stressors.
      Overall, the pattern of differences point to possible directions for adaptation
      of treatments for use with children with anxiety disorders served in public
      mental health systems.

PMID- 18046641
TI  - Management of the poor responder: the role of GnRH agonists and antagonists.
AB  - PURPOSE: Evaluate the relative benefit of various doses and regimens of GnRH
      agonists (GnRHa) and antagonists (GnRHant) in the management of the poor
      responder. METHODS: Review of English language publications with an emphasis on
      prospective randomized trials where available. RESULTS: The lack of a uniformly
      applied definition of the poor responder and dearth of prospective randomized
      trials make data analysis difficult. Traditional GnRHa flare and long luteal
      phase protocols do not appear to be beneficial. Reduction of GnRHa doses, "stop"
      protocols, and microdose GnRHa flare regimes all appear to enhance outcomes,
      although the relative benefit of one approach over another has not been
      conclusively demonstrated. GnRHant does improve outcomes in this patient
      population, although, in general, pregnancy rates appear to be lower in
      comparison to microdose GnRHa flare regimes. CONCLUSIONS: There is no one
      controlled ovarian hyperstimulation (COH) protocol which is best suited for all
      poor responders. Low dose GnRHa regimes appear to be most advantageous.
      Prediction of compromised response prior to cycle initiation by a thorough
      assessment of ovarian reserve as well as a careful review of past response should
      allow for selection of an appropriate COH protocol for each individual patient.

PMID- 18046642
TI  - Mutations of sodium channel alpha-subunit genes in Chinese patients with
      normokalemic periodic paralysis.
AB  - OBJECTIVE: In this study, we aim to investigate the clinical features and
      Mutations of sodium channel alpha-subunit (SCN4A) genes in Chinese patients with
      normokalemic periodic paralysis (normoKPP). METHODS: Six unrelated Chinese
      families with normoKPP were analyzed in clinical features. Genomic DNA was
      extracted from peripheral blood leukocytes and amplified with PCR. We screened
      all 24 exons of SCN4A gene with denaturing high performance liquid chromatography
      (DHPLC) technology, and then sequence analysis was performed in those who showed
      heteroduplex as compared with unaffected controls. RESULTS: The laboratory tests
      were within normal ranges. Electromyograms and electrocardiograms were normal.
      One muscle biopsy was performed with the patient in family 4 after a brief attack
      of normoKPP. Examination of light microscopy showed no changes, but electronic
      microscopy showed occasionally degenerating myofibers. The mutations of SCN4A
      genes were as follows: (1) Met1592Val occurred in family 1. (2) Val-781-Ile
      occurred with the patient and her father in family 4. (3) Both the patients had a
      novel mutation g2101a predicting the amino acid exchange Arg675Gln in family 5,
      which may be a disease-causing mutation. CONCLUSIONS: In addition to Val-781-Ile
      and Met1592Val, the mutation g2101a (Arg675Gln) may be the novel mutation of
      SCN4A genes in Chinese patients with normoKPP.

PMID- 18046643
TI  - Nonsteroidal anti-inflammatory drugs (NSAIDs) and mammographic density.
AB  - Mammographic density has been established as a strong risk factor for breast
      cancer while use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) has been
      associated with a reduction in risk of breast cancer. The hypothesis is that
      NSAIDs reverses the expression of prostaglandin E2, thereby reducing the local
      production of estrogens. This report describes the differences in mammographic
      densities by duration of NSAID use in a multiethnic population. Information for
      this analysis was available from two previous investigations: a nutritional
      intervention study with 218 women and a nested case-control study of breast
      density with 1274 women. On the basis of self-reported medication use from a
      questionnaire common to both investigations, women were categorized into no use,
      up to 1 year, 2-5 years, 6-10 years, and 11+ years. Screening mammograms were
      assessed for density using a computer-assisted method. We applied general linear
      models to calculate mean percent densities for each medication use category while
      adjusting for covariates. The analysis of the overall study population did not
      show a significant association between total NSAID use and mammographic density.
      Contrary to our hypothesis, women with long-term total NSAID use had non
      significantly higher densities than non-users. In addition, the results differed
      by menopausal status. Whereas the trend of higher densities with longer duration
      of total NSAID use was significant among postmenopausal women, breast density was
      slightly lower among premenopausal women with long-term NSAID use. Experimental
      studies need to be performed to study the effect, if any, of NSAID use on breast
      density.

PMID- 18046644
TI  - Effects of vitamin C on fibroblasts from sporadic Alzheimer's disease patients.
AB  - Several therapies for Alzheimer's Disease (AD) are currently under investigation.
      Some studies have reported that concentration of vitamins in biological fluids
      are lower in AD patients compared to control subjects and clinical evidence has
      shown the therapeutic potential of vitamin C and E in delaying AD progression.
      However, the molecular mechanism(s) that are engaged upon their administration in
      the APP metabolism in vitro or in vivo still need clarifying. Here, we
      investigate the effects of vitamin C supplementation, at physiological
      concentration, in skin fibroblasts obtained from SAD and FAD patients. This study
      shows that SAD patients' fibroblasts exhibited the exclusive appearance of C
      terminal fragments, derived from APP processing, without giving rise to the beta
      amyloid peptide, other than corresponding decreased levels of lysosomal enzymes,
      such as beta-hexosaminidase, alpha-mannosidase and cathepsins B, L, and D.

PMID- 18046645
TI  - Chemo-embolization for unresectable hepatocellular carcinoma with different sizes
      of embolization particles.
AB  - The purpose of this study was to evaluate the size responses and vascular
      responses to three different sizes of Embosphere (EMBS) embolization particles
      used for chemo-embolization in patients with unresectable hepatocellular
      carcinoma (HCC). Forty-seven patients with biopsy proven HCC treated with TACE
      using EMBS (Biosphere Medical, Rockland, MA, USA) were included in this study.
      EMBS are non-resorbable tris-acryl gelatin defined-size microspheres. Sixteen
      patients were treated with 40-120 micron (40-microm), 13 patients with 100-300
      (100-microm), and 18 patients with 300-500 (300-microm) EMBS particles. We
      measured the two-dimensional area and vascularity of the tumor index lesion on
      initial and subsequent CTs after treatment. Lesions were classified into four
      grades based on the degree of vascularity measured in 25% increments. Size of
      tumor after one treatment decreased by an average (avg) of 18% for 40-120-microm
      particles, 38% for 100-300-microm particles, and 17% for 300-500-microm
      particles. After three treatments, size decreased by an avg of 46% for 40-120
      microm particles, 76% for 100-300-microm particles, and 46% for 300-500-microm
      particles. Vascularity decrease was also measured after the first and third
      treatments, and defined as a decrease of one or more grades in tumor vascularity.
      Results were as follows (% of patients with decrease). For 40-120-microm
      particles: 1 and 3 treatments, 53% and 88% of patients. For 100-300-microm
      particles: 1 and 3 treatments, 60% and 88% of patients. For 300-500-microm
      particles: 1 and 3 treatments, 50% and 57% of patients. It was concluded the 100
      300-microm EMBS particles produce slightly higher responses.

PMID- 18046646
TI  - Health and humanitarian migrants' economic participation.
AB  - Refugees and immigrants being resettled in Australia on humanitarian grounds are
      known to have poorer health than other immigrants. Using data from the
      Longitudinal Surveys of Immigrants to Australia, the paper examines the influence
      of three measures of health-self-reported health status, the presence of a long
      term health condition and mental health status-on the economic participation of
      humanitarian migrants. Multivariate logistic regression is used to control for
      other factors known to affect immigrants' economic participation, such as age,
      skills and English language proficiency, to see if health has an independent
      effect. The results show that migrants with poor physical health are less likely
      than migrants with good health to be in the work force. Mental health status
      affects the economic participation of male but not female migrants. The findings
      provide important empirical evidence of the significant role of health in the
      economic integration of migrants of refugee background.

PMID- 18046647
TI  - Integrating epidemiological data into a mechanistic model of type 2 diabetes:
      validating the prevalence of virtual patients.
AB  - Mathematical models are playing an increasing role in understanding the
      complexity of multifactorial diseases like type 2 diabetes. The objective of this
      study was to validate a population of virtual patients against a real population
      of patients with type 2 diabetes. A population of virtual patients was created
      that incorporates different underlying pathogenic lesions consistent with a type
      2 diabetic phenotype. These virtual patients were created within the Metabolism
      PhysioLab platform, a non-linear coupled differential algebraic model that
      incorporates the salient causal mechanisms underlying glucose homeostasis and
      substrate metabolism. The weights of each individual virtual patient were
      determined to reproduce the diversity in a real type 2 diabetic population
      obtained from the NHANES III study. As a validation test, this virtual population
      reproduced a series of clinical studies that identify less invasive biomarkers
      for insulin sensitivity. This approach demonstrates how computational bridges can
      be constructed between statistical approaches common in epidemiology and
      deterministic approaches common in biomedical engineering.

PMID- 18046648
TI  - Dynamic simulation of bioprosthetic heart valves using a stress resultant shell
      model.
AB  - It is a widely accepted axiom that localized concentration of mechanical stress
      and large flexural deformation is closely related to the calcification and tissue
      degeneration in bioprosthetic heart valves (BHV). In order to investigate the
      complex BHV deformations and stress distributions throughout the cardiac cycle,
      it is necessary to perform an accurate dynamic analysis with a morphologically
      and physiologically realistic material specification for the leaflets. We have
      developed a stress resultant shell model for BHV leaflets incorporating a Fung
      elastic constitutive model for in-plane and bending responses separately.
      Validation studies were performed by comparing the finite element predicted
      displacement and strain measures with the experimentally measured data under
      physiological pressure loads. Computed regions of stress concentration and large
      flexural deformation during the opening and closing phases of the cardiac cycle
      correlated with previously reported regions of calcification and/or mechanical
      damage on BHV leaflets. It is expected that the developed experimental and
      computational methodology will aid in the understanding of the complex dynamic
      behavior of native and bioprosthetic valves and in the development of tissue
      engineered valve substitutes.

PMID- 18046649
TI  - Information retrieval in Tip of the Tongue states: new data and methodological
      advances.
AB  - Research on Tip of the Tongue (ToT) states has been used to determine whether
      access to syntactic information precedes access to phonological information. This
      paper argues that previous studies have used insufficient analyses when
      investigating the nature of seriality of access. In the first part of this paper,
      these complex issues are discussed and suitable analyses proposed. In the second
      part, new experimental data are presented. In Experiment 1, English speakers were
      asked to give information about mass/count status and initial phoneme of nouns,
      when in a ToT state. In Experiment 2, German speakers were asked to report
      grammatical gender and initial phoneme of nouns, when in a ToT state. Evidence
      that syntactic and phonological information are accessed independently was
      obtained for both languages. Implications for models of language production and
      further methodological issues in ToT research are discussed.

PMID- 18046650
TI  - Activating basic category exemplars in sentence contexts: a dynamical account.
AB  - This paper examines the influence of context on the processing of category names
      embedded in sentences. The investigation focuses on the nature of information
      available immediately after such a word is heard as well as on the dynamics of
      adaptation to context. An on-line method (Cross Modal Lexical Priming) was used
      to trace how this process unfolds in time. We found that the information
      available immediately after a category word is presented is not altered by the
      sentence context in which the word is immersed. Rather, the structure of
      availability of particular exemplars of the category resembles the typicality
      structure of a conceptual representation. The adaptation to context occurs later
      (between 300 and 450 ms after the category word) and takes the form of a rapid
      reorganization of the structure rather than a gradual activation of a
      contextually relevant exemplar. We claim that such data is best accounted for in
      a dynamical framework, where a coherent global structure emerges through locally
      guided self-organization.

PMID- 18046653
TI  - Incarceration and sexually transmitted infections: a neighborhood perspective.
AB  - The social dynamics of some communities are affected by the loss of significant
      numbers of people to prison and by the release of others who encounter the
      challenge of coping with the negative effects of the incarceration experience.
      The effects on communities are evident, in part, in the high rates of sexually
      transmitted infections (STIs) in North Carolina (NC) counties that have a high
      rate of incarceration. In the present study, we examined whether the same
      associations can be observed at the census tract level in one urban city of NC.
      To identify the mechanisms by which incarceration can affect the transmission of
      STIs, we conducted ethnographic interviews with ex-offenders and people who lost
      a sexual partner to prison. We found that census tract rates of incarceration
      were consistently associated with gonorrhea rates in the subsequent year. An
      increase of the percentage of census tract person-time spent in prison from 2.0%
      to 2.5% corresponded to a gonorrhea rate increase of 7.1 cases per 100,000 person
      years. The people interviewed spoke of sexual partnership changes including those
      left behind finding new partners, in part for help in making financial ends meet;
      men having sex with men for the first time in prison; and having multiple new
      partners upon reentry to the community. The statistical associations and stories
      of the effects of incarceration on sexual relationships provide additional
      evidence of unintended community health consequences of high rates of
      incarceration.

PMID- 18046660
TI  - Chromogranin a expression in phaeochromocytomas associated with von Hippel-Lindau
      syndrome and multiple endocrine neoplasia type 2.
AB  - Chromogranin A (CGA) is a major secretory protein present in the soluble matrix
      of chromaffin granules of neuroendocrine cells and tumours, such as
      phaeochromocytomas. CGA has several functions, some of which may be involved in
      the distinct phenotypic differences of phaeochromocytomas in patients with von
      Hippel-Lindau (VHL) syndrome compared to multiple endocrine neoplasia type 2 (MEN
      2). In this study, we therefore compared tumour and plasma levels of CGA in
      patients with phaeochromocytoma associated with the two syndromes. We show that
      phaeochromocytomas from MEN 2 patients express substantially more CGA than
      tumours from VHL patients at both the mRNA (3-fold greater) and protein (20-fold)
      level. We further show that relative to increases in plasma catecholamines,
      patients with phaeochromocytomas associated with MEN 2 have higher plasma
      concentrations of CGA than those with tumours in VHL syndrome. These data
      supplement other observations that phaeochromocytomas in VHL compared to MEN 2
      patients express lower amounts of catecholamines and other chromaffin granule
      cargo, such as chromogranin B and neuropeptide Y. Possibly the differences in
      tumour CGA expression may contribute to differences in secretory vesicle
      formation and secretion in the two types of tumours. Alternatively the
      differences in expression in CGA and other secretory constituents may reflect
      downregulation of the entire regulated secretory pathway in VHL compared to MEN 2
      tumours.

PMID- 18046654
TI  - Cocaine-mediated alteration in tight junction protein expression and modulation
      of CCL2/CCR2 axis across the blood-brain barrier: implications for HIV-dementia.
AB  - One of the hallmark features underlying the pathogenesis of HIV encephalitis is
      the disruption of blood-brain barrier (BBB). Cocaine, often abused by HIV
      infected patients, has been suggested to worsen the HIV-associated dementia (HAD)
      via unknown mechanisms. The objective of the present study was to explore the
      effects of cocaine on BBB permeability using human brain microvascular
      endothelial cells (HBMECs). Additionally, because the chemokine CCL2 and its
      receptor CCR2 play a crucial role in the recruitment of inflammatory cells into
      the central nervous system in HAD brains, we tested for the effect of cocaine in
      modulating the CCL2/CCR2 axis. Our findings suggest that exposure of HBMECs to
      cocaine correlated with the breakdown of ZO-1 tight junction protein and
      reorganization of the cytoskeleton resulting in stress fiber formation.
      Furthermore, cocaine also modulated upregulation of the CCL2/CCR2 axis in
      monocytes. These findings conform to the multifaceted effects of cocaine leading
      to accelerated progression of HIV-1 neuropathogenesis.

PMID- 18046661
TI  - Circadian blood pressure profile in patients with active Cushing's disease and
      after long-term cure.
AB  - Hypertension is a major feature of Cushing's disease, with the attendant increase
      in the rate of cardiovascular events. The circadian blood pressure profile also
      impacts cardiovascular risk and a few studies have shown that patients with
      Cushing's syndrome do not present the expected nocturnal blood pressure decrease
      and, further, that this alteration persists in short-range disease remission.
      These studies were performed by conventional discontinuous ambulatory pressure
      monitoring, a technique not devoid of limitations. Aim of our study was the
      assessment of blood pressure and heart rate profile by beat-to-beat noninvasive
      monitoring in twelve patients with active Cushing's disease (9 women and 3 men,
      age 33.3+/-2.36 years) and the assessment of its possible changes at short- (<1
      year) and long-term (2-3 years) follow-up after curative surgery. No nocturnal
      blood pressure dipping (i.e., decrease by 10% of daytime values) was observed in
      50% of patients both during active hypercortisolism and within 1 year from
      surgery. Recovery of blood pressure dipping profile was detected at long-term
      follow-up in a minority of patients. Daytime heart rate was higher in patients
      with active Cushing's disease and decreased over time after cure. In conclusion,
      patients with Cushing's disease present absent nocturnal blood pressure dipping
      and abnormal heart rate values which do not resolve after short-term remission of
      hypercortisolism and show only partial improvement in the long run. These
      findings identify additional cardiovascular risk factors for patients cured of
      Cushing's disease.

PMID- 18046662
TI  - sRAGE and esRAGE are not associated with peripheral or autonomic neuropathy in
      type 2 diabetes.
AB  - The receptor for glycation end-products RAGE was previously shown to play a
      central role in the development of diabetic neuropathy. The present study was
      aimed to investigate, whether plasma levels of the soluble forms of RAGE are
      associated with neuropathy in type 2 diabetes. One-hundred and eight patients
      were screened for peripheral and autonomic diabetic neuropathy using standardized
      screening tests. No differences in the levels of soluble RAGE or the more defined
      endogenous secretory RAGE were observed in patients categorized into having no,
      mild, moderate, or severe deficits in the neuropathy disability or symptom score.
      In bivariate analysis, neither soluble RAGE nor endogenous secretory RAGE
      correlated with the expiration to inspiration ratio of heart rate variability. In
      multivariate models, the neuropathy disability score was independently associated
      with age (beta=0.38, p<0.01), glomerular filtration rate (beta=0.28, p<0.01) and
      the presence of retinopathy (beta=0.27, p<0.01), while the neuropathy symptom
      score was associated with age (beta=0.31, p<0.01) and fasting glucose (beta=0.24,
      p<0.05). The expiration to inspiration ratio of heart rate variability was
      associated with age (beta=-0.42, p<0.01), the body-mass-index (beta=-0.28,
      p<0.01) and presence of retinopathy (beta=-0.19, p<0.05). In contrast to
      classical risk factors, plasma soluble RAGE and endogenous secretory RAGE are not
      associated with measures of diabetic neuropathy in type 2 diabetes patients.

PMID- 18046663
TI  - [Investigations concerning the head-trunk-coordination].
AB  - BACKGROUND: In the assessment of vertigo patients with suspected cervicocephalic
      somatosensory deficit, the studies published thus far have focused on reflectory
      systems like the cervico-ocular reflex or the postural systems. Our study
      examines the cervicocephalic kinesthetic sensibility of head and body
      coordination. We therefore introduce two preliminary test series: the "subjective
      zero chin-knee-angle of the occipital joints" and the "saccadic repositioning
      during trunk rotation". METHODS: Subjective recordings of dizziness complaints
      were done using the Dizziness Handicap Inventory. PATIENTS: The study population
      consisted of 24 patients with palpatory cervicocephalic somatosensory deficit
      (group I) and 23 patients with a central vestibular compensated unilateral
      vestibular deficit (group II). Twenty-two healthy patients served as controls.
      The aim of the study is to provide a detailed examination of the "subjective zero
      chin-knee-angle of the occipital joints" as well as a detailed discussion of
      "saccadic repositioning with trunk rotation" by three-dimensional
      videooculography (3D-VOG). RESULTS: We were able to separate patients with a
      cervicocephalic somatosensory deficit with the first test procedure and
      differentiate them from groups II and III. The second test procedure shows a
      significant difference between groups I and III. CONCLUSION: We conclude from the
      group difference that the recording of cervicocephalic kinesthetic sensibility is
      a further indication of disturbed cervical proprioception.

PMID- 18046665
TI  - Challenges for randomized controlled trials in nephrology: illustrations in
      vascular access science and care.
AB  - While randomized controlled trials (RCTs) are the gold standard for evidence in
      medicine, there is an overall paucity of RCTs in nephrology compared with other
      medical subspecialties. Consequently, the management of the dialysis population
      is often guided by nephrology clinical practice guidelines that are largely based
      on observational data or expert opinion. This review examines problems related to
      designing, conducting and completing RCTs in nephrology, highlighting major
      challenges, successes and frustrations, with specific examples as they pertain to
      the science of hemodialysis vascular access and their impact on clinical practice
      guidelines.

PMID- 18046666
TI  - Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes
      (LIRICO) randomized trial.
AB  - Microalbuminuria is a strong, consistent and independent risk factor for
      cardiovascular and renal disease in patients with diabetes and/or hypertension
      and in the general population. Several randomized trials have shown the efficacy
      of inhibiting the renin-angiotensin system (RAS) with angiotensin-converting
      enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) to prevent
      cardiovascular events and the progression of kidney disease. These 2 classes of
      drugs are equally effective for renal outcomes in patients with diabetic
      nephropathy, but only ACEIs have been found to significantly impact the risk of
      all-cause mortality, predominantly cardiovascular, in patients with diabetic
      nephropathy. Studies on the cardiorenal efficacy of combined therapy with ACEIs
      and ARBs in individuals with microalbuminuria or macroalbuminuria and other
      cardiovascular risk factors have been inconclusive. The Long-term Impact of RAS
      Inhibition on Cardiorenal Outcomes (LIRICO) study aims to address existing
      questions in this setting. This is a phase III, randomized, comparative,
      pragmatic trial with prospective randomized open blinded endpoint (PROBE) design.
      It will evaluate the comparative efficacy of combined therapy with ACEIs and ARBs
      versus monotherapy with either ACEIs or ARBs in improving cardiovascular and
      renal outcomes in microalbuminuric or macroalbuminuric individuals at cardiorenal
      risk. The study will enroll 2,100 patients, selected in a network of internal
      medicine, diabetology or nephrology outpatient clinics. Patients will be randomly
      allocated to ACEIs, ARBs or their combination. The study has been approved and
      funded by the Agenzia Italiana del Farmaco (A.I.F.A.) within the 2005 funding
      plan for independent research on drugs.

PMID- 18046667
TI  - The native arteriovenous fistula in 2007. Surveillance and monitoring.
AB  - In the past 5 years, some clinical trials have questioned the value of
      surveillance in managing vascular accesses. Although prolongation of access life
      span is an important end point, reduction of thrombotic events reduces patient
      risks resulting from loss of access patency. Most of the available evidence
      suggests that detection of stenosis and prevention of thrombosis is valuable.
      When a test indicates the likely presence of a stenosis, then venography or
      fistulography should be used to definitively establish the presence and degree of
      the stenosis. In most but not all cases, angioplasty should be performed if the
      stenosis is greater than 50% by diameter. The value of routine use of any
      surveillance technique for detecting anatomic stenosis alone, without concomitant
      functional assessment by measurement of access flow, venous pressure,
      recirculation or other physiologic parameters, has not been established. Stenotic
      lesions should not be repaired merely because they are present. If such
      correction is performed, then intraprocedural or periprocedural measurement of
      access flow (QA) or intra-access pressure should be conducted to demonstrate a
      functional improvement with a successful percutaneous transluminal angioplasty.

PMID- 18046668
TI  - The native arteriovenous fistula in 2007. Research needs.
AB  - Several research questions are open in the field of vascular access for
      hemodialysis. The present paper reviews both prognostic issues, such as the
      identification of factors for patient stratification before access insertion, and
      intervention questions, such as comparison of the advantages and disadvantages of
      different surgical solutions, the effects of different medications on vascular
      pathology, the different cannulation practices to prevent vessel wall lesions and
      technologies for early diagnosis of access dysfunction. Given that the quality of
      the available literature in nephrology is often suboptimal, nephrologists need to
      pay special attention to methodology issues before embarking on expensive
      multicenter studies.

PMID- 18046669
TI  - Sevelamer treatment strategy in peritoneal dialysis patients: conventional dose
      does not make best use of resources.
AB  - BACKGROUND: The significant incremental expense in the use of conventional
      sevelamer dose prompted us to evaluate the role of prescribing a lower dose of
      sevelamer. METHODS: To determine the optimum strategy for prescribing sevelamer
      in peritoneal dialysis patients, we conducted an open-label randomized study
      comparing the treat-to-goal strategy (4.0-g daily sevelamer dose) with lower
      sevelamer dose (1.2-g daily dose). RESULTS: Twenty-seven peritoneal dialysis
      patients with serum calcium x phosphorus product above 55 mg2/dL2 were recruited.
      Eighteen were randomized to the low-dose treatment group (1.2 g daily), and 9 to
      the treat-to-goal (4.0 g daily) group. Overall, significantly lower calcium x
      phosphorus product and serum phosphorus levels at 6 months were achieved by the
      treat-to-goal treatment. The proportions of patients who attained the Kidney
      Disease Outcomes Quality Initiative (K/DOQI) treatment target, however, did not
      differ significantly between the treat-to-goal and low-dose treatment groups
      (66.7% +/- 30.8% vs. 33.3% +/- 21.8%, p=0.10). The numbers needed to treat to
      benefit 1 patient who attains the K/DOQI recommendation are 1.5 patients (95%
      confidence interval [95% CI], 1.0-2.8) in the 4.0-g daily dose and 3 patients
      (95% CI, 1.8-8.7) in the 1.2-g daily dose group. Therefore, an extra 66.7% of
      subjects would be able to attain the treatment recommendation within the same
      budget if the daily dose of sevelamer used was 1.2 g instead of the usual 4.0 g.
      Compared with a 1.2-g daily dose of sevelamer, the 4.0-g daily dose had an
      incremental cost-effectiveness ratio (ICER) of US $2,353 per additional patient
      achieving the K/DOQI target. Multivariate analysis showed that only the calcium x
      phosphorus product after 1 month of sevelamer treatment was predictive of
      treatment response. CONCLUSIONS: Low-dose sevelamer treatment might be a cost
      effective approach, which is "good for many rather than best for a few."

PMID- 18046670
TI  - Urinary excretion of low molecular weight proteins in patients with pure
      monoclonal light chain proteinuria.
AB  - BACKGROUND: Because urinary low molecular weight protein (LMWP) measurement shows
      changes in renal integrity at an early stage, beta2-microglobulin (B2m), retinol
      binding protein (RBP) and alpha1-microglobulin (A1m) were evaluated in 24-hour
      urine collection of 65 patients with pure monoclonal light chain (MLC)
      proteinuria and in 47 patients with different kidney diseases (DKDs) for
      comparison. METHODS AND RESULTS: Albumin, kappa, lambda, A1m and B2m were
      measured by immunonephelometry. RBP was determined by ELISA. The mean values of
      LMWP quantitation were significant for origin of the disease (MLC and DKD)
      (p<0.05) and renal failure (RF) (p<0.001) (MANOVA). Tukey HSD test only showed
      significant differences for LMWP between MLC patients with RF and DKD patients
      without RF. The mean value of A1m was different between patients with and without
      RF in each group (p<0.05 for MLC, and p<0.01 for DKD). In the group without RF,
      the frequency of A1m excretion above 12 mg/L differed between MLC patients and
      DKD patients (p<0.01). CONCLUSION: A tubular dysfunction occurred in a great
      number of patients excreting pure MLC even in those with well-preserved renal
      function, as it did in patients with DKDs. In patients with MLC without RF, A1m
      might be measured for the early recognition of tubular involvement.

PMID- 18046671
TI  - Mass spectrometry analysis of IgA1 hinge region in patients with IgA nephropathy.
AB  - BACKGROUND: Physicochemical alterations of the IgA molecule are supposed to play
      a pathogenetic role in IgA nephropathy (IgAN). The present study was carried out
      to analyze the structural variety of O-glycans on the IgA1 hinge region in IgAN.
      Sera from 9 IgAN patients and 9 healthy controls were individually examined to
      evaluate the IgA1 content and binding lectins (jacalin and Helix aspersa), using
      enzyme-linked immunosorbent assay (ELISA) techniques. The IgA1 from pooled sera
      were separated by affinity chromatography (jacalin), and the fragment containing
      the hinge region was prepared by pyridylethylation and trypsin treatment. The IgA
      fragments containing the hinge glycopeptide (33-mer hinge peptide core (HP) + O
      glycans) were separated by jacalin affinity chromatography. Because we used
      jacalin, we only analyzed the Gal-3GalNAc residue containing IgA. The molecular
      weight (MW) of the IgA1 fragments was estimated using an ion trap mass
      spectrometer equipped with an electrospray ion source (ESI/MS). RESULTS: IgA1
      concentration in pathological sera was higher than in the control serum (p<0.01).
      Compared with controls, serum IgA1 from IgAN patients showed significantly
      greater binding to the 2 lectins, jacalin (p<0.01) and Helix aspersa (HA,
      p<0.001), which are specific for O-linked Gal-beta1,3-GalNAc and GalNAc,
      respectively. Analyses of pooled sera showed that the number of O-glycosidic
      chains was comparable in IgAN and normal sera. With regards to the individual
      residues, we found that IgAN sera contained less sugar and galactose and sialic
      acid moieties than sera from control subjects, was reduced in IgAN sera, while
      terminal N-acetylgalactosamine levels were higher when compared with normal
      serum. CONCLUSIONS: Abnormalities of hinge region O-linked glycans were confirmed
      using advanced spectrometry technology. The pathogenetic implications for
      aggregation and defective removal of IgA1 are discussed.

PMID- 18046672
TI  - A Mediterranean age-comorbidity prognostic index for survival in dialysis
      populations.
AB  - BACKGROUND: The most widely used prognostic indices for estimation of survival,
      including for dialysis patients, were described by Charlson, and an adaptation
      was proposed by Hemmelgarn for dialysis patients. We present the first age
      comorbidity prognostic index (ACPI) designed in a Mediterranean incident dialysis
      population and examine its concordance with other prognostic indices. METHODS:
      Incident dialysis patients were scored in relation to age and 11 diseases. Cox
      regression analysis was performed to construct multiple regression models, and
      diseases with a hazard ratio (HR) higher than 1.2 were included in the index. The
      impact of age was assessed by including it in a separate multivariate model.
      Scores were categorized in 3 levels of risk: low (0-1 points), medium (2-4
      points) and high levels (5 or more points). The probability of survival of each
      group was calculated according to the Kaplan-Meier method, and receiver operating
      characteristic (ROC) curves were plotted to examine the concordance with other
      prognostic indices. RESULTS: A cohort of 304 patients on hemodialysis (80%) and
      peritoneal dialysis was analyzed. Global mortality rate was 31% (93/304). The
      mean score was 4.41 +/- 2.84. Diseases that received the highest scores were
      ischemic heart disease (IHD) with chronic heart failure (CHF), and malignancies
      of less than 5 years of evolution. With regard to age, the maximum score was
      received by patients over 60 years old. The probability of survival at 3 years
      was 89%, 77% and 54% for low-, medium- and high-risk groups, respectively (log
      rank test, 19; p=0.0001). The ROC curves showed similar areas for our index
      (0.749), the Charlson index (0.758) and Hemmelgarn index (0.708), but our index
      scored higher than Charlson in older patients, IHD with CHF, CHF, peripheral
      vascular disease and systemic diseases. CONCLUSIONS: Although prospective
      external validation of this new index is required, this index adequately
      estimates the probability of survival at 3 years. The prognostic power of ACPI is
      similar to that of the Charlson index; however, relevant differences were found,
      concerning the weight of factors age, cardiovascular diseases and myocardial
      dysfunction. In end-stage renal disease we recommend estimating survival by
      indices established in incident dialysis patients, due to the particular comorbid
      conditions of this population.

PMID- 18046673
TI  - Cost-effectiveness of losartan in diabetic nephropathy: a Greek perspective.
AB  - BACKGROUND: Diabetic nephropathy is the primary cause of end-stage renal disease
      (ESRD), which involves substantial economic burden. The primary objective of this
      study was to estimate the potential effect of losartan on the costs associated
      with ESRD in patients with diabetic nephropathy in a Greek setting. A secondary
      aim was to approximate the direct health care cost of renal replacement therapy
      (RRT) in Greece. METHODS: A cost-effectiveness analysis was performed to compare
      losartan with placebo in patients with type 2 diabetes and nephropathy. Clinical
      data were derived from the RENAAL study. All costs were calculated from the
      perspective of the Greek social insurance system, in 2003 euros. Future costs
      were discounted at 3%. The time horizon was 3.5 years. Extensive sensitivity
      analyses were performed. RESULTS: The reduction in the number of ESRD days over
      3.5 years in patients treated with losartan reduced ESRD-related costs by
      3,056.54 euros, resulting in net cost savings of 1,665.43 euros per patient. Net
      cost savings increase thereafter, increasing to 2,686.48 euros per patient over a
      period of 4.0 years. The results were robust under a wide range of plausible
      assumptions. The weighted mean daily cost of RRT was estimated at 90.97 euros per
      patient. The total economic burden of RRT for the year 2003 has been estimated at
      304.773 million euros. CONCLUSIONS: This study demonstrated that treatment of
      patients with diabetic nephropathy in Greece with losartan is cost-effective, as
      it leads to important savings for the social insurance system by slowing the
      progression to ESRD.

PMID- 18046674
TI  - Fabry disease: renal biopsy-proven cases from China.
AB  - BACKGROUND: Fabry disease is a rare metabolic disorder resulting from deficient
      activity of the lysosomal enzyme alpha-galactosidase A (alpha-GalA). Renal
      involvement is the major cause of morbidity and mortality in male patients. Here,
      we describe the largest series ever reported for this condition in China.
      METHODS: Nine patients were enrolled in this study. Routine light microscopy
      (including toluidine blue staining), immunofluorescence and electron microscopic
      examinations were performed. We measured alpha-GalA activity in leukocyte and
      gene mutation analysis. Clinical and laboratory data of the patients were
      collected. RESULTS: Eight of the 9 patients were hemizygous males. Proteinuria
      was obvious in all patients. Three patients presented with mild renal function
      impairment. Light microscopy revealed glomeruli full of enlarged podocytes with
      abundant foamy cytoplasm. Toluidine blue stain revealed abundant cytoplasmic
      granular inclusions within the podocytes, tubular epithelial cells and
      endothelial cells of peritubular capillaries. Electron microscopy showed abundant
      electron-dense myelin figures within the podocyte cytoplasm. Arteriolar
      hyalinization and occlusion were also observed. Extrarenal manifestations,
      including acroparesthesia, hypohidrosis, abnormal electrocardiography and
      angiokeratoma were noted. No cornea verticillata or lenticular opacities were
      observed. These patients had about 0.3%-1.3% residual alpha-GalA activity in
      leukocytes. We identified a novel missense mutation (F273L) causing nonclassical
      Fabry disease. CONCLUSIONS: Fabry disease is relatively rare in China. Renal
      biopsy and specific staining is efficacious in the correct diagnosis of the
      disease. Discrepancies in the clinical manifestations of Fabry disease (i.e., eye
      disorders and hypertension) exist between cases found in China and those detailed
      in Western reports.

PMID- 18046675
TI  - Evaluation of serum anion gap in patients with HIV.
AB  - BACKGROUND: The anion gap (AG) is an important tool in the evaluation of
      metabolic acidosis. It is affected by many variables including serum albumin and
      globulin concentrations. HIV patients may have lower serum albumin and higher
      serum globulin concentrations. We hypothesized that the AG in HIV patients may
      differ from that of normal controls. PATIENTS AND METHODS: We reviewed medical
      records of 248 stable HIV patients and compared their laboratory variables to 312
      patients being evaluated for routine health maintenance in an outpatient setting.
      RESULTS: The average serum albumin concentration was not different in patients
      with HIV and normal controls (43 +/- 6 g/L vs. 45 +/- 4 g/L). The serum globulin
      concentration was significantly higher in the HIV patients when compared with
      that of normal controls (37 +/- 9 g/L vs. 28 +/- 6 g/L; p<0.05). The AG in the
      HIV patients was significantly lower than that of normal controls (9.4 +/- 1.9
      mmol/L vs. 10.8 +/- 2.7 mmol/L; p<0.05). The slope of the regression line that
      describes the inverse relationship between serum globulin and AG was 0.147 mmol
      per g/L. Using this slope, AG could be adjusted for abnormal serum globulin
      levels: adjusted anion gap = anion gap + 0.147 x (globulin - 29). CONCLUSION: Our
      results indicate that the AG is lower in HIV patients and that this decrement may
      be due to the increase in serum globulin concentrations. Since a high serum AG
      metabolic acidosis may be masked by a deceitfully normal AG in patients with
      elevated serum globulin concentrations, calculation of corrected AG should be
      undertaken to avoid a costly delay in diagnosis and treatment.

PMID- 18046676
TI  - Quality of life and its correlates in ambulatory hemodialysis patients.
AB  - BACKGROUND: In hemodialysis patients, quality of life (QOL) may vary across a
      range of individual conditions and social environments. In this study, we focused
      on ambulatory hemodialysis patients, examining their QOL compared with that of
      age-matched controls. Correlates of QOL in ambulatory hemodialysis patients were
      also examined. METHODS: QOL was evaluated by WHOQOL in ambulatory hemodialysis
      patients and age-matched controls. Correlations of QOL with age, sex, body mass
      index (BMI), functional performance, physical activity, cognitive function,
      psychiatric disorders, diabetes status, comorbidities, duration of dialysis
      therapy, adequacy of dialysis, biochemical variables and nutritional status were
      also examined in ambulatory hemodialysis patients. RESULTS: In WHOQOL, we found
      decreased psychological domain scores (19.8 vs. 21.6, p=0.012) and overall QOL
      (89.0 vs. 94.3, p=0.035) for ambulatory hemodialysis patients compared with age
      matched controls, especially in the items: enjoying life (p=0.032), feeling life
      has meaning (p=0.023), having opportunity to take leisure time (p=0.003) and
      being satisfied with sexual life (p=0.044). Patients with male sex, BMI >24 and
      duration of dialysis shorter than 5 years had lower overall QOL than controls.
      Male dialysis patients also had lower QOL than female patients. As for correlates
      of QOL in ambulatory hemodialysis patients, age, BMI and psychiatric disorders
      were negatively correlated. By contrast, premorbid and current satisfaction with
      personal health were positively correlated. CONCLUSIONS: QOL in ambulatory
      hemodialysis patients was lower than in age-matched controls. QOL in ambulatory
      hemodialysis patients was positively correlated with personal health satisfaction
      and negatively correlated with age, BMI and psychiatric disorders.

PMID- 18046677
TI  - Catastrophic antiphospholipid syndrome: report of 4 cases.
AB  - Catastrophic antiphospholipid syndrome (CAPS), described by Asherson in 1992, is
      a rare form of antiphospholipid syndrome resulting in multiorgan failure with a
      mortality rate of about 50%. The syndrome occurs in patients with either systemic
      lupus erythematosus and other rheumatic diseases (systemic sclerosis, rheumatoid
      arthritis, primary Sjogren syndrome) or alone. Whereas in "classic"
      antiphospholipid syndrome (APS), medium-large vessels are involved, a diffuse
      small vessel ischemia and thrombosis (microangiopathic disease) leading to a
      severe multiorgan dysfunction is predominant in CAPS. "Trigger" factors have been
      demonstrated in 45% of patients, but in the majority, they remain unknown. Not
      infrequently, CAPS arises in patients without any previous thrombotic history.
      The kidney is the organ most commonly affected, followed by the lung, the central
      nervous system, the heart and the skin. Disseminated intravascular coagulation
      occurs in approximately 13% of patients. The present study reports the clinical
      and serological features of 4 patients affected by this rare form of
      antiphospholipid syndrome. Nephrologists should be aware of the possibility of
      this syndrome as a cause of multiorgan failure since prompt recognition is
      essential for effective treatment.

PMID- 18046678
TI  - "Full house" proliferative glomerulonephritis: an unreported presentation of
      subacute infective endocarditis.
AB  - A severely ill 65-year-old man presented with symptoms of shortness of breath,
      edema and vasculitidic purpura over his lower extremities. He had severe mitral
      regurgitation which had not been surgically treated. Hematologic examination
      demonstrated leukocytosis with profound anemia. Other blood tests revealed
      impaired renal function, hypoalbuminemia, hypocomplementemia and mixed-type
      cryoglobulinemia. Urinalysis showed proteinuria, hematuria and pyuria, typical of
      a nephritic sediment. Renal biopsy indicated diffuse proliferative
      glomerulonephritis and a "full house" deposition in immunofluorescence study
      (positive for C3, C4, C1q, IgG, IgA and IgM), resembling the pathologic findings
      in class IV lupus nephritis. Although subacute bacterial endocarditis was
      initially suspected owing to a history of a predisposing valvular heart disease,
      probable vegetation shown by cardiac sonography and a clinical picture suggestive
      of a chronic infection, it was thought unlikely due to the entire afebrile course
      and initial sterile blood cultures. However, the blood cultures repeated 2 weeks
      after admission grew 3 sets of viridans streptococci. Following a course of
      penicillin and gentamicin treatment, his renal function, anemia and abnormal
      urine sediments improved gradually. Diffuse proliferative glomerulonephritis is
      well known to occur in infective endocarditis. However, the "full house"
      immunostaining in immunofluorescence study has never been reported. This case
      adds a new entity to the differential diagnosis of "full house" immune complex
      related glomerulonephritis and exemplifies the need to maintain a high index of
      suspicion for underlying infectious disorders when facing glomerulonephritic or
      vasculitic syndrome.

PMID- 18046679
TI  - Spider-like oligothiophenes.
AB  - Careful analysis and comparison of optical and electrochemical data available in
      recent literature for multi-thiophene molecular assemblies suggested a few basic
      rules for the design of structurally simple and easily accessible oligothiophenes
      endowed with properties not far from those exhibited by much more complex and
      synthetically demanding architectures. The synthesis and computational
      investigation of three examples of a class of oligothiophenes (spider-like)
      tailored according to these indications are reported together with their
      exhaustive optical and electrochemical characterization. The new compounds (T9 5,
      T14 6, T19 7) are characterized by a thiophene, a 2,2'-bithiophene and a
      2,2',5',2''-terthiophene unit (the spider body) fully substituted with 5-(2,2'
      bithiophen)yl pendants (the spider legs). Absorption and electrochemical data are
      in good agreement and point to a high pi-conjugation level, comparable to those
      displayed by much larger assemblies. Electrode potential cycling in proximity of
      the first oxidation peak affords fast and reproducible formation of conducting,
      highly stable [TXn]m films, mainly consisting of dimers (m=2). Electrooxidation
      kinetic experiments on deuterium-labelled T9 5, coupled to laser-desorption
      ionization mass spectroscopy on the resulting dimer demonstrated that the
      coupling process is extremely regioselective in the alpha positions of the more
      conjugated pentathiophene chain. The optical and the electrochemical properties
      of the films are reported and discussed. A peculiar feature is their impressive
      charge-trapping ability. Spider-like oligothiophenes are promising materials for
      applications as active layers in multifunctional organic devices.

PMID- 18046680
TI  - Photocatalytic cleavage of single TiO2/DNA nanoconjugates.
AB  - TiO(2)/DNA nanoconjugates were successfully fabricated by using the catechol
      moiety as a binding functional group, which was confirmed by steady-state
      absorption and fluorescence spectroscopies. Upon UV irradiation, the
      photocatalytic cleavage of the TiO(2)/DNA nanoconjugates was observed at the
      single-molecule level by using wide-field fluorescence microscopy. The decrease
      in the number of conjugates, which was estimated from the luminescent spots due
      to semiconductor quantum dots modified at the DNA strand, was significantly
      inhibited by a single A/C mismatch in the DNA sequences. This result strongly
      suggests that the migration of holes, which are injected from the photoexcited
      TiO(2) into the DNA, through the DNA bases plays an important role in the
      photocatalytic cleavage of the conjugates. The influences of the photogenerated
      reactive oxygen species (ROS) on the cleavage efficiency were also examined.
      According to the experimental results, it was concluded that oxidation of the
      catechol moiety and/or the DNA damage are key reactions in this process.

PMID- 18046681
TI  - Azulene-moiety-based ligand for the efficient sensitization of four near-infrared
      luminescent lanthanide cations: Nd3+, Er3+, Tm3+, and Yb3+.
AB  - The ML(4) complexes formed by reaction between the bidentate azulene-based ligand
      diethyl 2-hydroxyazulene-1,3-dicarboxylate (HAz) and several lanthanide cations
      (Pr(3+), Nd(3+), Gd(3+), Ho(3+), Er(3+), Tm(3+), Yb(3+), and Lu(3+)) have been
      synthesized and characterized by elemental analysis, FT-IR vibrational
      spectroscopy and electrospray ionization mass spectroscopy. Spectrophotometric
      titrations have revealed that four Az(-) ligands react with one lanthanide cation
      to form the ML(4) complex in solution. Studies of the luminescence properties of
      these ML(4) complexes demonstrated that Az(-) is an efficient sensitizer for four
      different near-infrared emitting lanthanide cations (Nd(3+), Er(3+), Tm(3+), and
      Yb(3+)); the resulting complexes have high quantum yield values in CH(3)CN. The
      near-infrared emission arising from Tm(3+) is especially interesting for biologic
      imaging and bioanalytical applications since biological systems have minimal
      interaction with photons at this wavelength. Hydration numbers, representing the
      number of water molecules bound to the lanthanide cations, were obtained through
      luminescence lifetime measurements and indicated that no molecules of
      water/solvent are bound to the lanthanide cation in the ML(4) complex in
      solution. The four coordinated ligands protect well the central luminescent
      lanthanide cation against non-radiative deactivation from solvent molecules.

PMID- 18046682
TI  - Unprecedented aromatic homolytic substitutions and cyclization of amide-iminyl
      radicals: experimental and theoretical study.
AB  - Amide-iminyl radicals are versatile and efficient intermediates in cascade
      radical cyclizations of N-acylcyanamides. They are easily trapped by alkenes or
      (hetero-)aromatic rings and cyclize into a series of new heterocyclic compounds
      which bear a pyrroloquinazoline moiety. As an illustration of the synthetic
      importance of these compounds, the total synthesis of the natural antitumor
      compound luotonin A was achieved through a tin-free radical cascade cyclization
      process. Not only do amide-iminyl radicals lead to new tetracyclic heterocycles
      but these nitrogen-centered radical species also react in aromatic homolytic
      substitutions. Indeed, the amide-iminyl radical moiety unprecedentedly displaces
      methyl, methoxy, and fluorine radicals from an aromatic carbon atom. This seminal
      reaction in the field of radical chemistry has been developed experimentally and
      its mechanism has additionally been investigated by a theoretical study.

PMID- 18046683
TI  - Xylogranatins F-R: antifeedants from the Chinese mangrove, Xylocarpus granatum, a
      new biogenetic pathway to tetranortriterpenoids.
AB  - Thirteen limonoids with a new carbon skeleton, the xylogranatins F-R (1-13), have
      been isolated from the seeds of a Chinese mangrove, Xylocarpus granatum; two
      recently reported compounds, xylogranatins C and D were also isolated. Their
      structures were elucidated on the basis of spectroscopic data and chemical
      methods. The absolute configurations of these compounds were determined by using
      the modified Mosher MTPA ester method and by quantum chemical circular dichroism
      (CD) calculations. Xylogranatins F-Q are the first aromatic B-ring limonoids
      found in nature. They belong to two substructural classes, of which one (1-3)
      contains a pyridine ring while the other one (4-12) contains a central furan
      core. Xylogranatins C and R can be considered to be key biosynthetic
      intermediates, while xylogranatin D, the only limonoid found so far with a carbon
      skeleton that conatains a C(30)-C(9) linkage, is apparently an artifact. The
      structures of these compounds suggest a new biogenetic pathway to
      tetranortriterpenoids. Xylogranatins F, G and R were found to exhibit marked
      antifeedant activity against the third instar larvae of Mythimna separata
      (Walker) at a concentration of 1 mg mL(-1). The most potent compound tested was
      xylogranatin G. Its AFC(50) (concentration for 50 % antifeedant activity) values
      at the exposure times of 24 and 48 h were 0.31 and 0.30 mg mL(-1), respectively.

PMID- 18046684
TI  - Ligand-directed immobilization of proteins through an esterase 2 fusion tag
      studied by atomic force microscopy.
AB  - Atomically flat mica surfaces were chemically modified with an alkyl
      trifluoromethyl ketone, a covalent inhibitor of esterase 2 from Alicyclobacillus
      acidocaldarius, which served as a tag for ligand-directed immobilization of
      esterase-linked proteins. Purified NADH oxidase from Thermus thermophilus and
      human exportin-t from cell lysates were anchored on the modified surfaces. The
      immobilization effectiveness of the proteins was studied by atomic force
      microscopy (AFM). It was shown that ligand-esterase interaction allowed specific
      attachment of exportin-t and resulted in high-resolution images and coverage
      patterns that were comparable with immobilized purified protein. Moreover, the
      biological functionality of immobilized human exportin-t in forming a quaternary
      complex with tRNA and the GTPase Ran-GTP, and the dimension changes before and
      after complex formation were also determined by AFM.

PMID- 18046685
TI  - Glyceryl-S-acyl carrier protein as an intermediate in the biosynthesis of
      tetronate antibiotics.
AB  - The biosynthetic pathway to the unusual tetronate ring of certain polyketide
      natural products, including the antibiotics abyssomicin and tetronomycin (TMN)
      and the antitumour compound chlorothricin (CHL), is presently unknown. The gene
      clusters governing chlorothricin and tetronomycin biosynthesis both contain a
      gene encoding an atypical member of the FkbH family of enzymes, which has
      previously been shown to synthesise glyceryl-S-acyl carrier protein (ACP) as the
      first step in production of unusual extender units for modular polyketide
      biosynthesis. We show here that purified recombinant FkbH-like protein, Tmn16,
      from the TMN gene cluster catalyses the efficient transfer of a glyceryl moiety
      from D-1,3-bisphosphoglycerate (1,3-BPG) to either of the dedicated ACPs, Tmn7a
      and ChlD2, to form glyceryl-S-ACP, which directly implicates this compound as an
      intermediate in tetronate biosynthesis as well. Neither Tmn16 nor Tmn7a produced
      glyceryl-S-ACP when incubated, respectively, with analogous ACP and FkbH-like
      proteins from a known extender-unit pathway; this indicates a highly selective
      channelling of glycolytic metabolites into tetronate biosynthesis.

PMID- 18046686
TI  - Synthesis of 3- and 6-sulfonylindoles from ortho-alkynyl-N-sulfonylanilines by
      the use of Lewis acidic transition-metal catalysts.
AB  - Gold-catalyzed reactions of ortho-alkynyl-N-sulfonylanilines produced the
      corresponding 3-sulfonylindoles in good to high yields. For example, the reaction
      of N-mesyl-N-methyl-2-(1-pentynyl)aniline, N-mesyl-N-methyl-2-(phenylethynyl)
      aniline, and 2-ethynyl-N-mesyl-N-methylaniline in the presence of 10 mol % of
      AuBr3 in toluene at 80 degrees C gave 3-mesyl-1-methyl-2-propylindole, 3-mesyl-1
      methyl-2-phenylindole, and 3-mesyl-1-methylindole in 95, 92, and 71% yield,
      respectively. Furthermore, we found that the reactions of 2-alkynyl-6-methoxy-N
      sulfonyl-anilines in the presence of indium catalyst (InBr3) afforded the
      corresponding 6-sulfonylindoles as the major product in good yields. For example,
      the reaction of 6-methoxy-N-methyl-2-(1-pentynyl)-N-tosylaniline in the presence
      of 5 mol % of InBr3 in toluene at 80 degrees C gave an 87:13 mixture of 7-methoxy
      1-methyl-2-propyl-6-tosylindole and 7-methoxy-1-methyl-2-propyl-3-tosylindole in
      95% yield. Most probably, the gold-catalyzed reactions of ortho-alkynyl-N
      sulfonylanilines proceed through a [1,3] sulfonyl migration, whereas the indium
      catalyzed cyclizations of 2-alkynyl-6-methoxy-N-sulfonylanilines, which produce 6
      sulfonylindoles, proceed by an unprecedented [1,7] sulfonyl migration.

PMID- 18046687
TI  - Free-radical-based, specific desulfurization of cysteine: a powerful advance in
      the synthesis of polypeptides and glycopolypeptides.

PMID- 18046688
TI  - NMR spectroscopy: pushing the limits of sensitivity.

PMID- 18046689
TI  - 1,7-Diaza[12]annulene derivatives? 100-year-old pyridinium salts!

PMID- 18046690
TI  - Stereocontrolled intramolecular aziridination of glycals: ready access to
      aminoglycosides and mechanistic insights from DFT studies.
AB  - Stereocontrolled intramolecular aziridination of the glycal-derived sulfamates
      offers a highly efficient strategy to divergently prepare aminoglycosides.
      Rhodium-catalyzed nitrogen-atom transfer to C==C bonds formed semistable
      aziridines, which were subjected to various nucleophiles (C, O, S, and N) to give
      cyclic sulfamate-containing aminosugar derivatives selectively. The second
      nucleophilic displacement of sulfonyloxy moieties of [1,2,3]-oxathiazepane-2,2-
      dioxides allows straightforward access to aminoglycosides with selective alpha-
      or beta-linkages. This approach is operationally simple, complements existing
      methods, and is a versatile protocol for the synthesis of polyfunctionalized
      amino sugars. In addition, the mechanism of the rhodium-catalyzed intramolecular
      aziridination of glycals and its ring-opening reaction was extensively studied by
      using DFT calculations.

PMID- 18046692
TI  - Water compatible gold(III)-catalysed synthesis of unsymmetrical ethers from
      alcohols.
AB  - An efficient and broad-scoped method for the preparation of unsymmetrical ethers
      from alcohols catalysed by the simplest and least expensive gold catalyst,
      NaAuCl(4), is described for the first time. The procedure enables the
      etherification of benzylic and tertiary alcohols with moderate to good yields
      under mild conditions with low catalyst loading. Symmetrical ethers, the usual
      side products in the etherification of alcohols, were not detected in this case.
      The formation of the racemic ether from a chiral benzyl alcohol suggests the
      intermediacy of a carbocation, which has not previously been postulated for gold
      catalysed reactions involving alcohols.

PMID- 18046691
TI  - Asymmetric synthetic access to the hetisine alkaloids: total synthesis of (+)
      nominine.
AB  - A dual cycloaddition strategy for the synthesis of the hetisine alkaloids has
      been developed, illustrated by a concise asymmetric total synthesis of (+)
      nominine (7). The approach relies on an early-stage intramolecular 1,3-dipolar
      cycloaddition of a 4-oxido-isoquinolinium betaine dipole with an ene-nitrile
      dipolarophile. Subsequent late-stage pyrrolidine-induced dienamine
      isomerization/Diels-Alder cascade allows for rapid construction of the carbon-
      nitrogen polycyclic skeleton within this class of C(20)-diterpenoid alkaloids.

PMID- 18046694
TI  - Recent developments in CE and CEC of peptides.
AB  - The article brings a comprehensive survey of recent developments and applications
      of high-performance capillary electromigration methods, zone electrophoresis,
      ITP, IEF, affinity electrophoresis, EKC, and electrochromatography, to analysis,
      preparation, and physicochemical characterization of peptides. New approaches to
      the theoretical description and experimental verification of electromigration
      behavior of peptides and to methodology of their separations, such as sample
      preparation, adsorption suppression, and detection, are presented. Novel
      developments in individual CE and CEC modes are shown and several types of their
      applications to peptide analysis are presented: conventional qualitative and
      quantitative analysis, purity control, determination in biomatrices, monitoring
      of chemical and enzymatical reactions and physical changes, amino acid and
      sequence analysis, and peptide mapping of proteins. Some examples of
      micropreparative peptide separations are given and capabilities of CE and CEC
      techniques to provide important physicochemical characteristics of peptides are
      demonstrated.

PMID- 18046693
TI  - {7-[Bis(carboxymethyl)amino]coumarin-4-yl}methoxycarbonyl derivatives for
      photorelease of carboxylic acids, alcohols/phenols, thioalcohols/thiophenols, and
      amines.
AB  - Light-induced release of biomolecules from inactive precursor molecules
      represents a powerful method to study cellular processes with high temporal and
      spatial resolution. Here we report the synthesis and photochemistry of a series
      of {7-[bis(carboxymethyl)amino]coumarin-4-yl}methyl carboxylates, carbonates,
      carbamates, and thiocarbonates as potential phototriggers for compounds with
      COOH, OH, NH(2), and SH functions. The compounds are soluble in aqueous buffer,
      show low fluorescence, and are efficiently photolysed by irradiation with UV/Vis
      or IR light to release carboxylates, alcohols, phenols, amines, thioalcohols, or
      thiophenols.

PMID- 18046695
TI  - Enhanced analytical power of SDS-PAGE using machine learning algorithms.
AB  - We aim to demonstrate that a complex plant tissue protein mixture can be reliably
      "fingerprinted" by running conventional 1-D SDS-PAGE in bulk and analyzing gel
      banding patterns using machine learning methods. An unsupervised approach to
      filter noise and systemic biases (principal component analysis) was coupled to
      state-of-the-art supervised methods for classification (support vector machines)
      and attribute ranking (ReliefF) to improve tissue discrimination, visualization,
      and recognition of important gel regions.

PMID- 18046696
TI  - The chicken egg yolk plasma and granule proteomes.
AB  - Using 1-D SDS-PAGE, LC-MS/MS, and MS(3), we identified 119 proteins from chicken
      egg yolk, 86 of which were not identified in yolk previously. Proteins were
      roughly quantitated by calculating their exponentially modified protein abundance
      index (emPAI) to classify them as major or minor yolk components, and to estimate
      their distribution between yolk plasma and yolk granular fraction. The proteins
      with highest abundance were serum albumin, the vitellogenin cleavage products,
      apovitellenins, IgY, ovalbumin, and 12 kDa serum protein with cross-reactivity to
      beta2-microglobulin. In addition yolk contained many other serum and egg white
      proteins, the proteases nothepsin and thrombin, numerous protease inhibitors, and
      antioxidative enzymes, such as superoxide dismutase and glutathione peroxidase.
      Among the moderately abundant proteins were two alpha2-macroglobulin-like
      proteins different from egg white alpha2-macroglobulin, and the major biotin
      binding protein of yolk. An unexpected identification was that of the eggshell
      matrix protein ovocleidin-116, which was previously thought to be eggshell
      specific. The list of chicken egg yolk proteins provided in this report is by far
      the most comprehensive at present and may serve as a starting point for the
      characterization of less well-known yolk proteins.

PMID- 18046697
TI  - The larger acenes: versatile organic semiconductors.
AB  - Acenes have long been the subject of intense study because of the unique
      electronic properties associated with their pi-bond topology. Recent reports of
      impressive semiconductor properties of larger homologues have reinvigorated
      research in this field, leading to new methods for their synthesis,
      functionalization, and purification, as well as for fabricating organic
      electronic components. Studies performed on high-purity acene single crystals
      revealed their intrinsic electronic properties and provide useful benchmarks for
      thin film device research. New approaches to add functionality were developed to
      improve the processability of these materials in solution. These new
      functionalization strategies have recently allowed the synthesis of acenes larger
      than pentacene, which have hitherto been largely unavailable and poorly studied,
      as well as investigation of their associated structure/property relationships.

PMID- 18046698
TI  - Configurationally labile lithiated O-benzyl carbamates: application in asymmetric
      synthesis and quantum chemical investigations on the equilibrium of
      diastereomers.
AB  - The title compounds were generated by deprotonation of different benzyl-type
      carbamates with sec-butyllithium in the presence of chiral diamines (-)-sparteine
      or diisopropyl and di-tert-butyl bis(oxazoline)s. These lithiated species exhibit
      configurational lability at -78 degrees C. In the case of the chiral di-tert
      butyl bis(oxazoline), the equilibrium of the epimeric complexes can be used
      synthetically to obtain highly enantioenriched secondary benzyl carbamates. The
      enantiodetermining step was proven to be a dynamic thermodynamic resolution. The
      absolute configurations of the products were determined, and the stereochemical
      pathways of selected substitution reactions were thus elucidated. High-level
      quantum chemical investigations were performed to gain insight into the
      experimentally investigated system. To obtain an accuracy for the energy
      difference (delta deltaH) between two epimeric complexes of about 0.5 kcal mol(
      1) as well as the correct sign, a theoretical procedure was established. It
      included geometry optimization at the dispersion-corrected DFT level, computation
      of zero-point vibrational energies, and single-point SCS-MP2 energy calculations
      with large atomic-orbital basis sets.

PMID- 18046699
TI  - Organophosphorus pesticide exposure decreases sperm quality: association between
      sperm parameters and urinary pesticide levels.
AB  - Several studies have suggested that human semen quality has declined over the
      past decades and some of them have associated it with occupational exposure to
      pesticides. However, most of these studies have not been associated with a
      reliable exposure level and have been designed mostly as cross-sectional studies.
      The present work evaluates, in a longitudinal follow-up study, the effect of
      organophosphate pesticides (OP) at three occupational exposure levels on semen
      quality. In addition, the study examined the association between OP urinary
      levels and sperm parameters in exposed and unexposed workers. A total of 139
      semen samples from 52 volunteers were assessed. Urinary OP levels were measured
      by gas-liquid chromatography. The results revealed that the poorest semen quality
      was found among the subjects with the highest OP exposure and the highest urinary
      OP levels. Seasonal variations in sperm concentration and sperm count were
      registered. The results showed a significant decrease in total sperm count among
      subjects with the highest exposure to OP. Further studies assessing the effects
      of OP on male reproductive health should be controlled by the variability in
      human sperm parameters, sperm seasonality, spermatogenesis time and the changing
      OP exposure level in men highly exposed to OP.

PMID- 18046700
TI  - Characterization of white matter alterations in phenylketonuria by magnetic
      resonance relaxometry and diffusion tensor imaging.
AB  - A multimodal MR study including relaxometry, diffusion tensor imaging (DTI), and
      MR spectroscopy was performed on patients with classical phenylketonuria (PKU)
      and matched controls, to improve our understanding of white matter (WM) lesions.
      Relaxometry yields information on myelin loss or malformation and may
      substantiate results from DTI attributed to myelin changes. Relaxometry was used
      to determine four brain compartments in normal-appearing brain tissue (NABT) and
      in lesions: water in myelin bilayers (myelin water, MW), water in gray matter
      (GM), water in WM, and water with long relaxation times (cerebrospinal fluid
      [CSF]-like signals). DTI yielded apparent diffusion coefficients (ADCs) and
      fractional anisotropies. MW and WM content were reduced in NABT and in lesions of
      PKU patients, while CSF-like signals were significantly increased. ADC values
      were reduced in PKU lesions, but also in the corpus callosum. Diffusion
      anisotropy was reduced in lesions because of a stronger decrease in the
      longitudinal than in the transverse diffusion. WM content and CSF-like components
      in lesions correlated with anisotropy and ADC. ADC values in lesions and in the
      corpus callosum correlated negatively with blood and brain phenylalanine (Phe)
      concentrations. Intramyelinic edema combined with vacuolization is a likely cause
      of the WM alterations. Correlations between diffusivity and Phe concentrations
      confirm vulnerability of WM to high Phe concentrations.

PMID- 18046701
TI  - A catheter tracking method using reverse polarization for MR-guided
      interventions.
AB  - To conduct interventional procedures in MRI, reliable visualization of
      interventional devices such as catheters is necessary. For this purpose, the use
      of inductively-coupled radio frequency (ICRF) coils has been proposed. Without a
      wired connection, the signal around the ICRF coil is amplified, enabling
      catheters to be visualized. The wireless connection allows easy handling of
      catheters, in some pulse sequences, however, it might be difficult to
      differentiate the catheters from anatomical background information. In this work,
      a novel ICRF coil visualization method, which allows separation of the catheter
      and the anatomical information by using the reverse and forward polarization
      modes of a coil, is proposed. This method allows images of the anatomy and the
      catheter to be combined into a color-coded image. First, an ICRF coil with
      decoupling diodes was constructed; we call this a receive-coupled RF (RCRF) coil.
      The RF safety profile of the RCRF coil is shown to be better than the ICRF coil.
      Second, to demonstrate the feasibility of this method, a receive-only birdcage
      coil without a hybrid coupler was constructed and then connected to a scanner as
      a two-channel phased-array coil. MR signals acquired from two channels were added
      after phase adjustments to create the reverse and forward polarization mode
      images. The reverse polarization mode image contained signal only from the RCRF
      coil, but the forward polarization mode displayed both anatomical information and
      the RCRF coil. The performance of this novel tracking method was tested in
      phantom and animal experiments. Color-coded images demonstrate the feasibility of
      the method to track catheters using RCRF coils.

PMID- 18046702
TI  - Temperature mapping considerations in the breast with line scan echo planar
      spectroscopic imaging.
AB  - A line-scan echo planar spectroscopic imaging (LSEPSI) sequence was used to
      serially acquire spectra from 4,096 voxels every 6.4 s throughout the breasts of
      nine female subjects in vivo. Data from the serial acquisitions were analyzed to
      determine the potential of the technique to characterize temperature changes
      using either the water frequency alone or the water-methylene frequency
      difference. Fluctuations of the apparent temperature change under these
      conditions of no heating were smallest using the water-methylene frequency
      difference, most probably due to a substantial reduction of motion effects both
      within and without the imaged plane. The approach offers considerable advantages
      over other methods for temperature change monitoring in the breast with magnetic
      resonance but suffers from some limitations, including the unavailability of
      lipid and water resonances in some voxels as well as a surprisingly large
      distribution of water-methylene frequency differences, which may preclude
      absolute temperature measurement.

PMID- 18046703
TI  - Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG
      micelles.
AB  - Pegylated, fluorescent, and paramagnetic micelles were developed. The micelles
      were conjugated with macrophage scavenger receptor (MSR)-specific antibodies. The
      abdominal aortas of atherosclerotic apoE-KO mice were imaged with T(1)-weighted
      high-resolution MRI before and 24 h after intravenous administration of the
      contrast agent (CA). Pronounced signal enhancement (SE) (up to 200%) was observed
      for apolipoprotein E knockout (apoE-KO) mice that were injected with MSR-targeted
      micelles, while the aortic vessel wall of mice injected with nontargeted micelles
      showed little SE. To allow fluorescence microscopy and optical imaging of the
      excised aorta, the micelles were made fluorescent by incorporating either a
      quantum dot (QD) in the micelle corona or rhodamine lipids in the micelle.
      Ultraviolet (UV) illumination of the aorta allowed the identification of regions
      with high macrophage content, while MSR-targeted rhodamine micelles could be
      detected with fluorescence microscopy and were found to be associated with
      macrophages. In conclusion, this study demonstrates that macrophages in apoE-KO
      mice can be effectively and specifically detected by molecular MRI and optical
      methods upon administration of a pegylated micellar CA.

PMID- 18046705
TI  - Design and characterization of a new irreversible responsive PARACEST MRI
      contrast agent that detects nitric oxide.
AB  - Irreversible responsive PARAmagnetic Chemical Exchange Saturation Transfer
      (PARACEST) MRI contrast agents constitute a new type of agent for molecular
      imaging. To investigate the utility of this approach, a novel PARACEST MRI
      contrast agent, Yb(III)-(1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid)
      orthoaminoanilide (Yb-DO3A-oAA), was developed that detects nitric oxide (NO).
      The agent exhibited two CEST effects at -11 ppm and +8 ppm, which were assigned
      to chemical exchange from amide and amine functional groups, respectively. The
      effects of pH, temperature, and concentration were investigated to characterize
      the complex and to optimize PARACEST detection. This responsive PARACEST MRI
      contrast agent incurred an irreversible covalent change in the presence of NO and
      O(2), which caused an irreversible disappearance of both PARACEST effects from MR
      images. The NO-dependent response of a relaxivity-based MRI contrast agent, Gd
      DO3A-oAA, was investigated for comparison. This report highlights the advantages
      of irreversible MRI contrast agents, demonstrates that large changes in PARACEST
      can be used to create a highly responsive agent, and indicates challenges that
      must be overcome to apply this type of contrast agent to in vivo biomedical
      applications in molecular imaging.

PMID- 18046706
TI  - Lung MRI using an MR-compatible active breathing control (MR-ABC).
AB  - This work introduces an MR-compatible active breathing control device (MR-ABC)
      that can be applied to lung imaging. An MR-ABC consists of a pneumotachograph for
      respiratory monitoring and an airway-sealing unit. Using an MR-ABC, the subjects
      were forced to suspend breathing for short time intervals, which were used in
      turn for data acquisition. While the breathing flow was stopped, data acquisition
      was triggered by ECG to achieve simultaneous cardiac and respiratory
      synchronization and thus avoid artifacts from blood flow or heart movement. The
      flow stoppage allowed a prolonged acquisition window of up to 1.5 sec. To
      evaluate the potential of an MR-ABC for segmented k-space acquisition, diaphragm
      displacement was investigated in five volunteers and compared with images
      acquired using breath-holding, a respiratory belt, and free breathing.
      Respiratory movement was comparatively low using the breath-hold approach, a
      respiratory belt or an MR-ABC. During free-breathing diaphragm displacement was
      comparatively large. To demonstrate the potential of an MR-ABC, lung MRI was
      performed using whole-chest 3D gradient-echo imaging, multislice turbo spin-echo
      (TSE) imaging, and short tau inversion recovery TSE (STIR-TSE). Cardiorespiratory
      synchronization was used for each sequence. None of the volunteers reported any
      discomfort or inconvenience when using an MR-ABC. Flow stoppage of up to 2.5 sec
      per breathing cycle was well tolerated, therefore allowing for a reduction of the
      total imaging time as compared to usage of a respiratory belt or MR navigator.

PMID- 18046707
TI  - Predictors of treatment in patients with chronic hepatitis C infection - role of
      patient versus nonpatient factors.
AB  - Treatment with interferon and ribavirin is effective in patients with chronic
      infection with hepatitis C virus (HCV). Previous data indicate that treatment
      rates are suboptimal. We sought to identify patient and provider-level predictors
      of treatment receipt in HCV by conducting a retrospective cohort study of 5701
      HCV patients in a large regional Veteran's Administration (VA) healthcare
      network. We also determined the degree of variation in treatment rates
      attributable to patient, provider, and facility factors. Three thousand seven
      hundred forty-three patients (65%) were seen by a specialist and 894 (15.7%)
      received treatment. Treatment rates varied from 6% to 29% across the 5 facilities
      included in the analysis. Patients were less likely to receive treatment if they
      were older [RR, 0.55; 95% CI, 0.45, 0.67), single (RR, 0.77; 95%CI, 0.67, 0.88),
      had hepatic dysfunction (RR, 0.73; 95%CI, 0.66, 0.89), had normal alanine
      aminotransferase (ALT) (RR, 0.73; 95%CI, 0.59, 0.89), had HCV genotype 1 (RR,
      0.78; 95%CI, 0.71, 0.86), were African American with genotype 1 (RR, 0.78; 95%
      CI, 0.71, 0.86), or were anemic (RR, 0.70; CI, 0.60, 0.89). In addition, patients
      evaluated by less experienced providers were 77% less likely to receive treatment
      than those evaluated by more experienced providers. The patient, provider, and
      facility factors explained 23%, 25%, and 7% of variation in treatment rates,
      respectively. CONCLUSION: These data suggest that although patient
      characteristics are important predictors of treatment in HCV, a significant
      proportion of variation in treatment rates is explained by provider factors.
      These potentially modifiable provider-level factors may serve as high-yield
      targets for future quality improvement initiatives in HCV.

PMID- 18046708
TI  - Glucocorticoid-induced leucine zipper: A key protein in the sensitization of
      monocytes to lipopolysaccharide in alcoholic hepatitis.
AB  - Glucocorticoid-induced leucine zipper (GILZ), a recently identified protein
      induced by glucocorticoids (GCs), inhibits the nuclear factor kappaB pathway and
      the activation of monocytes/macrophages by lipopolysaccharides (LPS). This study
      aimed to elucidate the contribution of GILZ to the pathogenesis of alcoholic
      hepatitis (AH): we (1) assessed GILZ expression in the livers of patients with AH
      and (2) treated patients with severe AH with GCs (prednisolone 40 mg/day) and
      studied the effect of GILZ modulation on circulating monocyte function. We
      quantified GILZ expression in the livers of 42 consecutive alcoholic patients (21
      with and 21 without AH). GILZ messenger RNA (mRNA) levels were lower in the
      livers of patients with AH versus those without AH (P < 0.05). We collected
      circulating monocytes from patients with severe AH before and 48 hours after GC
      treatment to quantify GILZ expression and cytokine secretion. GC treatment
      induced significantly higher levels of GILZ mRNA than that observed before
      treatment and impaired LPS-induced tumor necrosis factor-alpha (TNF-alpha) and
      regulated upon activation, normal T cell-expressed secretion (RANTES) by these
      monocytes. We transfected circulating monocytes with GILZ small interfering RNA
      (siRNA), specifically blocking GILZ expression, to demonstrate the role of GILZ
      in mediating GC effect. GILZ siRNA abrogated the effect of GC treatment on LPS
      induced TNF-alpha and RANTES secretion. CONCLUSION: Low expression of GILZ may
      contribute to liver inflammation in AH. GCs enhance GILZ expression, abrogating
      macrophage sensitivity to LPS and proinflammatory cytokine secretion. These
      findings may explain the beneficial effect of GC treatment in patients with
      severe AH.

PMID- 18046709
TI  - Adipokines and insulin resistance in chronic hepatitis C.

PMID- 18046711
TI  - Hepatic Niemann-Pick C1-like 1: The canalicular side of the coin.

PMID- 18046710
TI  - Hepatitis B virus infection initiates with a large surface protein-dependent
      binding to heparan sulfate proteoglycans.
AB  - Contrary to many other viruses, the initial steps of the hepatitis B virus (HBV)
      infection, including attachment to hepatocytes, specific receptor interactions,
      and membrane fusion, are unsolved. Using HepaRG cells as an in vitro cell culture
      system, we here report that HBV entry into hepatocytes depends on the interaction
      with the glycosaminoglycan (GAG) side chains of cell-surface-associated heparan
      sulfate proteoglycans. Binding to GAGs requires the integrity of the pre-S domain
      as a part of the large (L-) viral envelope protein. HBV infection was abrogated
      by incubation of virions with heparin, but not the structurally related GAGs
      chondroitin sulfate A, B, and C. Infection was also abolished by suramin, a known
      inhibitor of duck hepatitis B virus infection or highly sulfated dextran sulfate.
      Polycationic substances such as poly-L-lysine, polybrene, and protamine also
      prevented infection, however, by addressing cellular components. Enzymatic
      removal of defined acidic carbohydrate structures from the cell surface using
      heparinase I/III or the obstruction of GAG synthesis by sodium chlorate inhibited
      HBV infection of HepaRG cells and, moreover, led to a reduction of HBV cell
      surface binding sites. The biochemical analysis showed selective binding of L
      protein-enriched viral particles (virions or filaments) to heparin. GAG-dependent
      binding of HBV was improved by polyethylene glycol, a substance that specifically
      enhances HBV infection. CONCLUSION: HBV infection requires the initial attachment
      to the carbohydrate side chains of hepatocyte-associated heparan sulfate
      proteoglycans as attachment receptors. This interaction initializes the multistep
      entry process of HBV and cannot be bypassed by alternative routes.

PMID- 18046713
TI  - Seventy-two weeks of peginterferon and ribavirin for patients with partial early
      virologic response?

PMID- 18046714
TI  - Corticosteroid treatment in biliary atresia: Tonic or toast?

PMID- 18046715
TI  - Predicting prognosis in acute liver failure: Ammonia and the risk of cerebral
      edema.

PMID- 18046716
TI  - Therapy with vasoconstrictor drugs in cirrhosis: The time has arrived.

PMID- 18046717
TI  - Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis c
      genotype 1-infected slow responders.
AB  - In hepatitis C virus (HCV) genotype 1 infection, the duration of interferon-based
      therapy is a critical determinant in achieving sustained virologic response
      (SVR). Slow or late responders to peginterferon and ribavirin may benefit from an
      extended treatment course. We sought to determine if therapy extension could
      improve response rates in a United States population of slow responders. Slow
      response was defined by achieving at least a 2-log decrement in HCV RNA from
      baseline, yet having detectable HCV RNA at 12 weeks and undetectable HCV RNA at
      24 weeks (polymerase chain reaction, TaqMan, Roche; detection limit 10 IU/mL).
      Patients were treatment-naive, chronically infected genotype 1-infected slow
      responders to 1.5 mug/kg/week of peginterferon-alpha2b and 800-1400 mg/day of
      ribavirin and were randomly assigned 1:1 to complete a total of 48 or 72 weeks of
      therapy. Dose reductions and treatment discontinuations for adverse events or
      laboratory abnormalities were similar between the 2 treatment arms. End-of
      treatment response rates were similar in the 72-week group compared with those in
      the 48-week group (48% versus 45%; P value not significant). Overall, the rate of
      SVR was superior in patients treated for 72 weeks versus 48 weeks (38% versus
      18%, respectively; P = 0.026). CONCLUSION: Extending the treatment duration from
      48 weeks to 72 weeks in genotype 1-infected patients with slow virologic response
      to peginterferon-alpha2b and weight-based ribavirin significantly improves SVR
      rates. Treatment extension does not seem to increase the rate of dose reduction
      or therapy discontinuation.

PMID- 18046718
TI  - MARS and the failing liver-Any help from the outer space?

PMID- 18046719
TI  - Grb2-associated binder-1 plays a central role in the hepatocyte growth factor
      enhancement of hepatoma growth inhibition by K vitamin analog compound 5.
AB  - Compound 5 (Cpd 5), a K vitamin analog, has been shown to inhibit Hep3B human
      hepatoma cell growth in cultures and rat hepatoma growth in vivo through
      prolonged epidermal growth factor receptor (EGFR)-extracellular response kinase
      (ERK) phosphorylation, and hepatocyte growth factor (HGF) synergizes with Cpd 5
      to enhance the inhibition of Hep3B cell and rat hepatoma growth. To explore the
      mechanisms mediating the HGF/Cpd 5 synergy, we examined the possible involvement
      of the Grb2-associated binder-1 (Gab1) docking protein because it interacts with
      both EGFR and HGF receptor c-Met pathways. We found that HGF enhanced Cpd 5
      induced c-Met phosphorylation at Tyr-1349, a binding site for Gab1, resulting in
      increased c-Met binding to Gab1, and induced strong and prolonged Gab1 tyrosine
      phosphorylation. Prolonged Gab1 phosphorylation by HGF/Cpd 5 in turn enhanced the
      ability of Gab1 to bind to protein tyrosine phosphatase SHP2 and enhanced the
      activation of its downstream mitogen-activated protein kinase pathway. In
      contrast, this same HGF/Cpd 5 treatment inhibited Gab1 binding to
      phosphatidylinositol 3-kinase (PI3K), leading to the inactivation of the PI3K-Akt
      pathway. The inhibition of Akt phosphorylation by HGF/Cpd 5 further activated the
      Raf-MEK-ERK signaling cascade via an Akt-Raf1 interaction, leading to strong and
      prolonged ERK phosphorylation. The transfection of Hep3B cells with mutated Gab1
      (Gab1 Y627F), which had lost its ability to bind SHP2, antagonized HGF/Cpd 5
      induced ERK phosphorylation, whereas the transfection of Hep3B cells with mutated
      Gab1 3YF, which lost its ability to bind PI3K, further enhanced HGF/Cpd 5-induced
      ERK phosphorylation and cell growth inhibition. CONCLUSION: Gab1 plays a central
      role in regulating HGF/Cpd 5 synergy in their actions on Hep3B cell growth
      inhibition.

PMID- 18046720
TI  - Determinants of alcohol use and abuse: Impact of quantity and frequency patterns
      on liver disease.
AB  - More than 70% of alcohol is consumed by 10% of the population in the United
      States. Implicit in this statistic is that tremendous variation in the pattern of
      drinking (quantity, frequency, and duration) exists among alcohol consumers.
      Individuals who are binge or chronic drinkers will have different health outcomes
      than social drinkers. Therefore, knowing the pattern of drinking will shed light
      on how severely individuals are alcohol-dependent and on the extent of liver
      damage. Thus, these parameters assume particular relevance for the treatment
      providing physician. Genetic factors contribute substantially to differences in
      alcohol metabolism. Variations in the activities of the alcohol-metabolizing
      enzymes, cytosolic alcohol dehydrogenase and mitochondrial aldehyde
      dehydrogenase, in part determine blood alcohol concentration, thereby
      contributing to the predisposition to becoming alcohol-dependent and to
      susceptibility to alcohol-induced liver damage. Chronic alcohol consumption
      induces cytochrome P450 2E1, a microsomal enzyme that metabolizes alcohol at high
      concentrations and also metabolizes medications such as acetaminophen and
      protease inhibitors. Alcohol metabolism changes the redox state of the liver,
      which leads to alterations in hepatic lipid, carbohydrate, protein, lactate, and
      uric acid metabolism. The quantity and frequency of alcohol consumption severely
      impact the liver in the presence of comorbid conditions such as infection with
      hepatitis B or C and/or human immunodeficiency virus, type 2 diabetes,
      hemochromatosis, or obesity and thus have implications with respect to the extent
      of injury and response to medications. CONCLUSION: Knowledge of the relationships
      between the quantity, frequency, and patterns of drinking and alcoholic liver
      disease is limited. A better understanding of these relationships will guide
      hepatologists in managing alcoholic liver disease.

PMID- 18046721
TI  - Identification of resident hepatic stem cell populations.

PMID- 18046724
TI  - Coffee and hepatocellular carcinoma: Cause or confounding?

PMID- 18046722
TI  - Effects of rosiglitazone on methionine-choline deficient diet-induced
      nonalcoholic steatohepatitis.

PMID- 18046726
TI  - Noninvasive diagnosis of nonalcoholic fatty liver disease using serum biomarkers.

PMID- 18046730
TI  - Alzheimer's disease: trade-off for increased survival with atherosclerosis?

PMID- 18046732
TI  - Macrophage attenuation of neuronal excitability: implications for pathogenesis of
      neurodegenerative disorders.
AB  - Brain macrophages (and microglia) play a crucial role in central nervous system
      immune and inflammatory responses. They are also critical cells in the
      pathogenesis of neurodegenerative disorders. To understand how macrophages cause
      neural cell dysfunction, we investigated the effects of mouse bone marrow-derived
      macrophages (BMDMs) on rat cortical neuronal physiology in a BMDM-neuronal co
      culture system using whole-cell patch clamp techniques. When co-cultured with
      neuronal cells, BMDMs hyperpolarized the neuronal membrane and attenuated both
      spontaneous and electrically evoked firings through a decrease in membrane input
      resistance. The average duration of evoked action potentials (APs) and the
      latency to fire the APs, in response to a constant depolarizing current
      injection, were significantly increased by BMDMs. These results indicate that
      BMDMs attenuate neuronal excitability. Further investigation revealed that BMDMs
      hyperpolarize neuronal membranes by enhancing neuronal delayed rectifier
      potassium current (IK), which was blocked by tetraethylammonium. This BMDM
      induced attenuation on neuronal excitability may contribute to the pathogenesis
      of neuronal dysfunction and damage as seen in neurodegenerative disorders.

PMID- 18046731
TI  - Modulation of innate immunity by copolymer-1 leads to neuroprotection in murine
      HIV-1 encephalitis.
AB  - Virus-infected and immune-competent mononuclear phagocytes (MP; perivascular
      macrophages and microglia) drive the neuropathogenesis of human immunodeficiency
      virus type 1 (HIV-1) infection. Modulation of the MP phenotype from
      neurodestructive to neuroprotective underlies adjunctive therapeutic strategies
      for human disease. We reasoned that, as Copolymer-1 (Cop-1) can induce
      neuroprotective activities in a number of neuroinflammatory and neurodegenerative
      disorders, it could directly modulate HIV-1-infected MP neurotoxic activities. We
      now demonstrate that, in laboratory assays, Cop-1-stimulated virus-infected human
      monocyte-derived macrophages (MDM) protect against neuronal injury. Severe
      combined immune-deficient (SCID) mice were stereotactically injected with HIV-1
      infected human MDM, into the basal ganglia, to induce HIV-1 encephalitis (HIVE).
      Cop-1 was administered subcutaneously for 7 days. In HIVE mice, Cop-1 treatment
      led to anti-inflammatory and neuroprotective responses. Reduced micro- and
      astrogliosis, and conserved NeuN/MAP-2 levels were observed in virus-affected
      brain regions in Cop-1-treated mice. These were linked to interleukin-10 and
      brain-derived neurotrophic factor expression and downregulation of inducible
      nitric oxide synthase. The data, taken together, demonstrate that Cop-1 can
      modulate innate immunity and, as such, improve disease outcomes in an animal
      model of HIVE.

PMID- 18046733
TI  - Worry facilitates corticospinal motor response to transcranial magnetic
      stimulation.
AB  - Like other forms of emotion, anxiety has been theoretically linked to preparation
      for action. Worry is a type of anticipatory anxiety and the hallmark of
      generalized anxiety disorder. Research has shown that worry is associated with
      vigilance to threat cues and increased muscle tension, which may in part be
      explained by motor facilitation that accompanies preparation for action. This
      study assessed corticospinal motor responses during worry using transcranial
      magnetic stimulation (TMS). Participants received TMS during a worry induction,
      during motor imagery, and during mental arithmetic, while electromyography and
      force were measured. TMS over the primary motor cortex elicited larger
      corticospinal motor responses during worry than mental arithmetic and smaller
      responses than motor imagery of maximum voluntary contraction of targeted
      muscles. These findings suggest that the association between worry and motor
      preparation cannot be explained by high cognitive load and provide further
      support for theoretical accounts emphasizing the role of action preparation in
      anxiety.

PMID- 18046735
TI  - Optimizing risk reduction in screening for Down syndrome.

PMID- 18046734
TI  - Testing NMDA receptor block as a therapeutic strategy for reducing ischaemic
      damage to CNS white matter.
AB  - Damage to oligodendrocytes caused by glutamate release contributes to mental or
      physical handicap in periventricular leukomalacia, spinal cord injury, multiple
      sclerosis, and stroke, and has been attributed to activation of AMPA/kainate
      receptors. However, glutamate also activates unusual NMDA receptors in
      oligodendrocytes, which can generate an ion influx even at the resting potential
      in a physiological [Mg2+]. Here, we show that the clinically licensed NMDA
      receptor antagonist memantine blocks oligodendrocyte NMDA receptors at
      concentrations achieved therapeutically. Simulated ischaemia released glutamate
      which activated NMDA receptors, as well as AMPA/kainate receptors, on mature and
      precursor oligodendrocytes. Although blocking AMPA/kainate receptors alone during
      ischaemia had no effect, combining memantine with an AMPA/kainate receptor
      blocker, or applying the NMDA blocker MK-801 alone, improved recovery of the
      action potential in myelinated axons after the ischaemia. These data suggest NMDA
      receptor blockers as a potentially useful treatment for some white matter
      diseases and define conditions under which these blockers may be useful
      therapeutically. Our results highlight the importance of developing new
      antagonists selective for oligodendrocyte NMDA receptors based on their
      difference in subunit structure from most neuronal NMDA receptors.

PMID- 18046736
TI  - A developmental approach to violence, hostile attributions, and paranoid thinking
      in adolescence.
AB  - Research within the area of paranoid thinking has focused primarily on adults and
      has only recently looked at the effects during the critical life stage of
      adolescence, with even less research in the context of the juvenile justice
      system. This article aims to explore the relationship between antisocial
      behaviour in adolescence and the development of paranoid thinking, set within
      wider contexts that surround the juvenile justice system. The information
      presented is drawn from both the current research and the clinical experiences of
      those working in adolescent forensic psychiatry services. The relationships with
      other disorders such as conduct disorder, ADHD, PTSD, and depression are also
      explored.

PMID- 18046737
TI  - Examining the effectiveness of an intervention designed for the restoration of
      competency to stand trial.
AB  - This study examined the effectiveness of the Fitness Game, an intervention
      created for the restoration of competency to stand trial. Of 28 participants who
      completed either the experimental or control intervention at Hawai'i State
      Hospital (HSH), it was found that both groups had significant pretest to posttest
      improvements on Understanding and Appreciation subsets of the MacArthur
      Competence Assessment Tool-Criminal Adjudication (MacCAT-CA). However, there was
      no statistically significant difference between the groups on competency
      measures, indicating that the Fitness Game was not significantly more effective
      at restoring competency than non-legal programming. In other words, individuals
      committed to a psychiatric hospital for care and treatment were as likely to
      improve as those receiving additional specialized competency restoration
      treatment.

PMID- 18046738
TI  - No skin off my back: retribution deficits in psychopathic motives for punishment.
AB  - When deciding a criminal's punishment, people typically exhibit both retributive
      and consequentialist motives in their decision making, though retribution's role
      may be stronger. This study aimed to discern possible functions of retribution by
      examining a population predicted to be deficient in retributive drive.
      Participants who rated either high or low in psychopathic traits read stories
      about a homicide. These stories were designed to evoke both retribution and the
      consequentialist motive of behavior control by varying, respectively, criminal
      intent and likelihood of recidivism. The participants then recommended a length
      of confinement for the offender. Individuals high in psychopathic traits were
      uniquely insensitive to retributive cues, and they were particularly
      consequentialist in their punishment of criminal offenders. These results clarify
      aspects of psychopathic aggression and corroborate the hypothesis that
      retribution may stabilize cooperative behavior.

PMID- 18046739
TI  - Death qualification and prejudice: the effect of implicit racism, sexism, and
      homophobia on capital defendants' right to due process.
AB  - Two hundred venirepersons from the 12th Judicial Circuit in Bradenton, Florida
      completed the following measures: (1) one question that measured their level of
      support for the death penalty; (2) one question that categorized their death
      qualification status; (3) 23 questions that measured their attitudes toward the
      death penalty (ATDP); (4) 22 questions that assessed their attitudes toward women
      (ATW); (5) 25 questions that measured their level of homophobia (H); (6) seven
      questions that assessed their level of modern racism (MR); (7) eight questions
      that measured their level of modern sexism (MS); and (8) standard demographic
      questions. Results indicated that as death-penalty support increased participants
      exhibited more positive attitudes toward the death penalty, more negative
      attitudes toward women, and higher levels of homophobia, modern racism, and
      modern sexism. Findings also suggested that death-qualified venirepersons
      exhibited more positive attitudes toward the death penalty and higher levels of
      homophobia, modern racism, and modern sexism. Finally, more positive attitudes
      toward the death penalty were correlated with more negative attitudes toward
      women and higher levels of homophobia, modern racism, and modern sexism. Legal
      implications are discussed.

PMID- 18046740
TI  - Application of the behavioral investigative support system for profiling
      perpetrators of serial sexual assaults.
AB  - The authors developed a data-based profiling system in order to support offender
      profiling. The system stored incident records of prior offenders. Inputting
      offence details of an unsolved incident, a probability score was assigned to each
      prior offender in the system; the score represented the behavioral similarity
      with the unsolved incident. The system then ranked all offenders in the system
      according to the probability scores, and prioritized the high-ranked offenders as
      possible suspects. Moreover, the system inferred the characteristics of unknown
      offenders by accumulating characteristics of the high-ranked offenders. The
      system achieved promising accuracy, especially for linking crimes to
      perpetrators. In 45 out of 81 simulation trials, the target offenders were
      retrieved as a rank score of 1 from among 868 sex offenders.

PMID- 18046741
TI  - When is profiling possible? Offense planning and aggression as moderators in
      predicting offender age from victim age in stranger rape.
AB  - Debate continues with regard to the possibility of inferring an offender's
      characteristic features from crime scene details (the process of so-called
      "offender profiling"). We argue that psychology generally has benefited from
      appreciating context in predicting behavior. In the same way, profiling would
      benefit from an appreciation of context in predicting characteristics. This
      "reverse" process is contingent on various "if...then" relationships. As one
      example, this paper demonstrates how profiling offender age from victim age is
      contingent on (i) the level of planning and (ii) the level of aggression
      displayed during the offense. Eighty-five stranger rape case records formed the
      data set. Moderated regression analysis revealed that victim age is a significant
      predictor of offender age only in cases where the offender has (i) shown evidence
      of planning the attack and/or (ii) acts in a gratuitously aggressive manner. The
      theoretical bases for these findings may lie in the extent to which offenders
      disparately plan and target victims and how extreme aggressiveness in stranger
      rapes may relate to a near-peer proxy for an offender's anger. The implications
      of the results for the processes and methods involved in offender profiling
      suggest that certain crime scene factors can have differential moderating effects
      on predictive outcomes.

PMID- 18046742
TI  - Toward a psychopathology of self-control theory: the importance of narcissistic
      traits.
AB  - Research on self-control and related constructs is central to individual-level
      explanations of antisocial behavior. However, less research attention has been
      paid to the psychopathological underpinnings of self-control. The current study
      explores relationships between self-control and psychiatric symptoms, head
      injury, trauma history, substance use, guiltlessness and narcissistic traits in a
      statewide population of juvenile offenders. Results support the importance of
      these variables, in particular narcissistic traits, in better explicating
      theories of self-control. Implications for research on the psychopathological
      underpinnings of self-control are highlighted.

PMID- 18046743
TI  - A National Survey of State Legislation defining mental retardation: implications
      for policy and practice after Atkins.
AB  - In Atkins v. Virginia 2002, the U.S. Supreme Court held that the Eighth Amendment
      prohibits executing offenders who are mentally retarded. Rather than adopting a
      uniform definition of mental retardation, the court charged each state with
      defining mental retardation in a manner that enforces the constitutional
      restriction. An unanswered question is how states define mental retardation after
      Atkins, which has implications for capital defendants and forensic evaluators who
      conduct capital mitigation evaluations. This project identified the statutory
      definitions of mental retardation in each state, and grouped the definitions
      based on consistency with accepted clinical criteria for mental retardation.
      Results show that definitions of mental retardation vary considerably by state.
      The large majority of states, both overall and specifically among death penalty
      states, use criteria for mental retardation that are not entirely consistent with
      accepted clinical standards. As such, it is not clear whether the majority of
      states are effectuating the intent of Atkins. The implications of these findings
      for both policy and practice are discussed.

PMID- 18046744
TI  - Police practices and perceptions regarding juvenile interrogation and
      interrogative suggestibility.
AB  - Recent media coverage has highlighted cases in which young suspects were wrongly
      convicted because they provided interrogation-induced false confessions. Although
      youth may be more highly suggestible and easily influenced by authority than
      adults, police are trained to use the same psychologically coercive and deceptive
      tactics with youth as with adults. This investigation is the first standard
      documentation of the reported interrogation practices of law enforcement and
      police beliefs about the reliability of these techniques and their knowledge of
      child development. Participants were 332 law enforcement officers who completed
      surveys about interrogation procedures and developmental issues pertaining to
      youth. Results indicated that, while police acknowledge some developmental
      differences between youth and adults, there were indications that (1) how police
      perceive youth in general and how they perceive and treat them in the
      interrogation context may be contradictory and (2) their general view is that
      youth can be dealt with in the same manner as adults.

PMID- 18046745
TI  - Human pigmentation variation: evolution, genetic basis, and implications for
      public health.
AB  - Pigmentation, which is primarily determined by the amount, the type, and the
      distribution of melanin, shows a remarkable diversity in human populations, and
      in this sense, it is an atypical trait. Numerous genetic studies have indicated
      that the average proportion of genetic variation due to differences among major
      continental groups is just 10-15% of the total genetic variation. In contrast,
      skin pigmentation shows large differences among continental populations. The
      reasons for this discrepancy can be traced back primarily to the strong influence
      of natural selection, which has shaped the distribution of pigmentation according
      to a latitudinal gradient. Research during the last 5 years has substantially
      increased our understanding of the genes involved in normal pigmentation
      variation in human populations. At least six genes have been identified using
      genotype/phenotype association studies and/or direct functional assays, and there
      is evidence indicating that several additional genes may be playing a role in
      skin, hair, and iris pigmentation. The information that is emerging from recent
      studies points to a complex picture where positive selection has been acting at
      different genomic locations, and for some genes only in certain population
      groups. There are several reasons why elucidating the genetics and evolutionary
      history of pigmentation is important. 1) Pigmentation is a trait that should be
      used as an example of how misleading simplistic interpretations of human
      variation can be. It is erroneous to extrapolate the patterns of variation
      observed in superficial traits such as pigmentation to the rest of the genome. It
      is similarly misleading to suggest, based on the "average" genomic picture, that
      variation among human populations is irrelevant. The study of the genes
      underlying human pigmentation diversity brings to the forefront the mosaic nature
      of human genetic variation: our genome is composed of a myriad of segments with
      different patterns of variation and evolutionary histories. 2) Pigmentation can
      be very useful to understand the genetic architecture of complex traits. The
      pigmentation of unexposed areas of the skin (constitutive pigmentation) is
      relatively unaffected by environmental influences during an individual's lifetime
      when compared with other complex traits such as diabetes or blood pressure, and
      this provides a unique opportunity to study gene-gene interactions without the
      effect of environmental confounders. 3) Pigmentation is of relevance from a
      public health perspective, because of its critical role in photoprotection and
      vitamin D synthesis. Fair-skinned individuals are at higher risk of several types
      of skin cancer, particularly in regions with high UVR incidence, and dark-skinned
      individuals living in high latitude regions are at higher risk for diseases
      caused by deficient or insufficient vitamin D levels.

PMID- 18046746
TI  - Paranthropus boisei: fifty years of evidence and analysis.
AB  - Paranthropus boisei is a hominin taxon with a distinctive cranial and dental
      morphology. Its hypodigm has been recovered from sites with good stratigraphic
      and chronological control, and for some morphological regions, such as the
      mandible and the mandibular dentition, the samples are not only relatively well
      dated, but they are, by paleontological standards, reasonably-sized. This means
      that researchers can trace the evolution of metric and nonmetric variables across
      hundreds of thousands of years. This paper is a detailed review of half a
      century's worth of fossil evidence and analysis of P. boisei and traces how both
      its evolutionary history and our understanding of its evolutionary history have
      evolved during the past 50 years.

PMID- 18046747
TI  - Mother-infant cosleeping, breastfeeding and sudden infant death syndrome: what
      biological anthropology has discovered about normal infant sleep and pediatric
      sleep medicine.
AB  - Twenty years ago a new area of inquiry was launched when anthropologists proposed
      that an evolutionary perspective on infancy could contribute to our understanding
      of unexplained infant deaths. Here we review two decades of research examining
      parent-infant sleep practices and the variability of maternal and infant sleep
      physiology and behavior in social and solitary sleeping environments. The results
      challenge clinical wisdom regarding "normal" infant sleep, and over the past two
      decades the perspective of evolutionary pediatrics has challenged the supremacy
      of pediatric sleep medicine in defining what are appropriate sleep environments
      and behaviors for healthy human infants. In this review, we employ a biocultural
      approach that integrates diverse lines of evidence in order to illustrate the
      limitations of pediatric sleep medicine in adopting a view of infants that
      prioritizes recent western social values over the human infant's biological
      heritage. We review what is known regarding infant sleeping arrangements among
      nonhuman primates and briefly explore the possible paleoecological context within
      which early human sleep patterns and parent-infant sleeping arrangements might
      have evolved. The first challenges made by anthropologists to the pediatric and
      SIDS research communities are traced, and two decades of studies into the
      behavior and physiology of mothers and infants sleeping together are presented up
      to the present. Laboratory, hospital and home studies are used to assess the
      biological functions of shared mother-infant sleep, especially with regard to
      breastfeeding promotion and SIDS reduction. Finally, we encourage other
      anthropologists to participate in pediatric sleep research using the unique
      skills and insights anthropological data provide. By employing comparative,
      evolutionary and cross-cultural perspectives an anthropological approach
      stimulates new research insights that influence the traditional medical paradigm
      and help to make it more inclusive. That this review will potentially stimulate
      similar research by other anthropologists is one obvious goal. That this article
      might do so makes it ever more possible that anthropologically inspired work on
      infant sleep will ultimately lead to infant sleep scientists, pediatricians, and
      parents becoming more informed about the consequences of caring for human infants
      in ways that are not congruent with their evolutionary biology.

PMID- 18046749
TI  - Mobile DNA elements in primate and human evolution.
AB  - Roughly 50% of the primate genome consists of mobile, repetitive DNA sequences
      such as Alu and LINE1 elements. The causes and evolutionary consequences of
      mobile element insertion, which have received considerable attention during the
      past decade, are reviewed in this article. Because of their unique mutational
      mechanisms, these elements are highly useful for answering phylogenetic
      questions. We demonstrate how they have been used to help resolve a number of
      questions in primate phylogeny, including the human-chimpanzee-gorilla trichotomy
      and New World primate phylogeny. Alu and LINE1 element insertion polymorphisms
      have also been analyzed in human populations to test hypotheses about human
      evolution and population affinities and to address forensic issues. Finally,
      these elements have had impacts on the genome itself. We review how they have
      influenced fundamental ongoing processes like nonhomologous recombination,
      genomic deletion, and X chromosome inactivation.

PMID- 18046750
TI  - Mummies.
AB  - Mummies are human remains with preservation of nonbony tissue. Mummification by
      natural influences results in so-called natural mummies, whereas mummification
      induced by active (human) intervention results in so-called artificial mummies,
      although many cultures practiced burial rites, which to some degree involved both
      natural and artificial mummification. Since they are so uniquely well-preserved,
      mummies may give many insights into mortuary practices and burial rites.
      Specifically, the presence of soft tissues may expand the scope of
      paleopathological studies. Many recent mummy studies focus on the development and
      application of nondestructive methods for examining mummies, including
      radiography, CT-scanning with advanced three-dimensional visualizations, and
      endoscopic techniques, as well as minimally-destructive chemical, physical, and
      biological methods for, e.g., stable isotopes, trace metals, and DNA. This
      article discusses mummification and gives a presentation of various key mummy
      finds and a brief history of mummy studies. A description of the extant key
      technologies of natural and medical science that are applied in mummy studies is
      given; along with a discussion of some of the major results in terms of
      paleopathology. It is also shown how mummy studies have contributed much to the
      knowledge of the cultural habits and everyday life of past populations. Finally
      the impact of mummy studies on analyses of mortuary practices and cultural
      history is discussed.

PMID- 18046751
TI  - The biology of the colonizing ape.
AB  - Hominin evolutionary history is characterized by regular dispersals, cycles of
      colonization, and entry into novel environments. This article considers the
      relationship between such colonizing capacity and hominin biology. In general,
      colonizing strategy favors rapid rates of reproduction and generalized rather
      than specialized biology. Physiological viability across diverse environments
      favors a high degree of phenotypic plasticity, which buffers the genome from
      selective pressures. Colonizing also favors the capacity to access and process
      information about environmental variability. We propose that early hominin
      adaptive radiations were based upon the development of such capacities as
      adaptations to unstable Pliocene environments. These components came together,
      along with fundamental changes in morphology, behavior, and cognition in the
      genus Homo, who exploited them in subsequent wider dispersals. Middle Pleistocene
      hominins and modern humans also show development of further traits, which
      correspond with successful probing of, and dispersals into, stressful
      environments. These traits have their precursors in primate or ape biology, but
      have become more pronounced during hominin evolution. First, short interbirth
      intervals and slow childhood growth allow human females to provision several
      offspring simultaneously, increasing the rate of reproduction in favorable
      conditions. This allows rapid recovery from population crashes, or rapid
      population growth in new habitats. Second, despite high geographical phenotypic
      variability, humans have high genetic unity. This is achieved by a variety of
      levels of plasticity, including physiology, behavior, and technology, which
      reduce the need to commit to genetic adaptation. Hominin behavior may
      increasingly have shaped both the ecological niches occupied and the selective
      pressures acting back on the genome. Such selective pressures may have been
      exacerbated by population dynamics, predicted to both derive from, and favor, the
      colonizing strategy. Exposure to ecological variability is likely to have
      generated particular selective pressures on female biology, favoring increasing
      steering of offspring ontogeny by maternal phenotype. We propose that the concept
      of hominins as "colonizing apes" offers a novel unified model for interpreting
      the suite of traits characteristic of our genus.

PMID- 18046752
TI  - The evolution of human reproduction: a primatological perspective.
AB  - Successful reconstruction of any aspect of human evolution ideally requires broad
      based comparisons with other primates, as recognition of general principles
      provides a more reliable foundation for inference. Indeed, in many cases it is
      necessary to conduct comparisons with other placental mammals to test
      interpretations. This review considers comparative evidence with respect to the
      following topics relating to human reproduction: (1) size of the testes, sperm,
      and baculum; (2) ovarian processes and mating cyclicity; (3) placentation and
      embryonic membranes; (4) gestation period and neonatal condition; (5) brain
      development in relation to reproduction; and (6) suckling and age at weaning.
      Relative testis size, the size of the sperm midpiece, and perhaps the absence of
      a baculum indicate that humans are adapted for a mating system in which sperm
      competition was not a major factor. Because sizes of mammalian gametes do not
      increase with body size, they are increasingly dwarfed by the size of the female
      reproductive tract as body size increases. The implications of this have yet to
      be explored. Primates have long ovarian cycles and humans show an average
      pattern. Menstruation is completely lacking in strepsirrhine primates, possibly
      weakly present in tarsiers and variably expressed in simians. The only other
      mammals reliably reported to show menstruation are bats. Three hypotheses have
      been proposed to explain the evolution of menstruation (eliminating sperm-borne
      pathogens; reducing the metabolic cost of a prepared uterine lining; occurrence
      as a side-effect of physiological changes), but no consensus has emerged.
      Copulation at times other than the periovulatory period is not unique to humans,
      and its occurrence during pregnancy is widespread among mammals. Although the
      human condition is extreme, extended copulation during the ovarian cycle is the
      norm among simian primates, in stark contrast to prosimians, in which mating is
      typically restricted to a few days when the female is in oestrus. The model of
      regular mid-cycle ovulation in simians is questionable. Gestation periods
      calculated on that basis show greater variability than in other mammals, and
      evidence from laboratory breeding colonies indicates that an extended mating
      period is matched by an extended period in which conception can occur. New
      evidence indicates that the noninvasive placentation found in strepsirrhine
      primates is not primitive after all. Furthermore, comparative studies reveal that
      such noninvasive placentation is not "inefficient". Evolution of highly invasive
      placentation in haplorhine primates is probably linked instead to immunological
      factors. Primates have relatively long gestation periods, and humans are average
      in this respect. However, there is evidence that humans show greater maternal
      investment during pregnancy in comparison with apes. Although the human neonate
      matches the typical precocial pattern of primates in most respects, a fetal
      pattern of brain growth continues for a year after birth, such that the human
      infant is "secondarily altricial" in terms of its dependence on parental care.
      Nevertheless, the "natural" lactation period of humans is probably about 3 years,
      fitting the expectation in comparison to other hominoids.

PMID- 18046753
TI  - Shifting adaptive landscapes: progress and challenges in reconstructing early
      hominid environments.
AB  - Since Darwin situated humans in an evolutionary framework, much discussion has
      focused on environmental factors that may have shaped or influenced the course of
      human evolution. Developing adaptive or causal perspectives on the morphological
      and behavioral variability documented in the human fossil record requires
      establishing a comprehensive paleoenvironmental context. Reconstructing
      environments in the past, however, is a complex undertaking, requiring
      assimilation of diverse datasets of varying quality, scale, and relevance. In
      response to these difficulties, human evolution has traditionally been
      interpreted in a somewhat generalized framework, characterized primarily by
      increasing aridity and seasonality periodically punctuated by pulses or intervals
      of environmental change, inferred largely from global climatic records. Although
      these broad paradigms provide useful heuristic approaches for interpreting human
      evolution, the spatiotemporal resolution remains far too coarse to develop
      unambiguous causal links. This challenge has become more acute as the emerging
      paleoenvironmental evidence from equatorial Africa is revealing a complex pattern
      of habitat heterogeneity and persistent ecological flux throughout the interval
      of human evolution. In addition, recent discoveries have revealed significant
      taxonomic diversity and substantially increased the geographic and temporal range
      of early hominids. These findings raise further questions regarding the role of
      the environment in mediating or directing the course of human evolution. As a
      consequence, it is imperative to critically assess the environmental criteria on
      which many theories and hypotheses of human evolution hinge. The goals here are
      to 1) compile, review, and evaluate relevant paleoecological datasets from
      equatorial Africa spanning the last 10 Ma, 2) develop a hierarchical perspective
      for developing and evaluating hypotheses linking paleoecology to patterns and
      processes in early hominid evolution, and 3) suggest a conceptual framework for
      modeling and interpreting environmental data relevant to human evolution in
      equatorial Africa.

PMID- 18046754
TI  - Summary of contributions to GAW15 Group 13: candidate gene association studies.
AB  - Here we summarize the contributions to Group 13 of the Genetic Analysis Workshop
      15 held in St. Pete Beach, Florida, on November 12-14, 2006. The focus of this
      group was to identify candidate genes associated with rheumatoid arthritis or
      surrogate outcomes. The association methods proposed in this group were diverse,
      from better known approaches, such as logistic regression for single nucleotide
      polymorphism (SNP) analysis and haplotype sharing tests to methods less familiar
      to genetic epidemiologists, such as machine learning and visualization methods.
      The majority of papers analyzed Genetic Analysis Workshop 15 Problems 2
      (rheumatoid arthritis data) and 3 (simulated data). The highlighted points of
      this group analyses were: (1) haplotype-based statistics can be more powerful
      than single SNP analysis for risk-locus localization; (2) considering linkage
      disequilibrium block structure in haplotype analysis may reduce the likelihood of
      false-positive results; and (3) visual representation of genetic models for
      continuous covariates may help identify SNPs associated with the underlying
      quantitative trait loci.

PMID- 18046755
TI  - Summary of contributions to GAW15 Group 16: processing/normalization of
      expression traits.
AB  - Here, we summarize the contributions to group 16 of Genetic Analysis Workshop 15,
      held in Florida, U.S.A. The theme of this group was preprocessing of expression
      quantitative trait loci (eQTL) studies using the Affymetrix platform. The
      objective of the Genetic Analysis Workshop 15 problem 1 dataset was to use
      transcript levels that are measured using DNA microarrays as quantitative traits
      and localize the genes or other features of the DNA that control gene expression
      by quantitative trait loci linkage analyses. All contributors of this group used
      the microarray expression profiles (problem 1) data. Various approaches and
      questions were examined to investigate the effects of preprocessing methods
      and/or gene filtering on the interpretation of data, specifically on heritability
      estimates of gene expression and on linkage results. In addition, some
      contributors focused on the statistical issues involved in large-scale genetic
      analyses of quantitative traits that account for or build composite phenotypes
      from a large number of correlated traits. Since the true eQTLs are not known in
      the problem 1 data, results from the 11 studies cannot be fully evaluated for the
      methods employed. However, several common trends were found. All reports
      concluded that preprocessing statistical analyses may have an important impact on
      eQTL analyses and on the identification of cis-/trans-regulators and/or major
      biological pathways.

PMID- 18046756
TI  - Introduction to Genetic Analysis Workshop 15 summaries.
AB  - The 15th biennial Genetic Analysis Workshop (GAW15) took place November 11-15,
      2006 in St. Pete Beach, Florida. The workshop's primary focus was on the
      appropriate linkage, association, and other analyses of the increasingly large
      datasets generated by genetics research. A record number of participants (N=350)
      contributed 252 papers to GAW15. These contributions were organized into 17
      presentation groups, with a range of 11 to 18 papers in each group (median of 15
      papers per group). The data sets--or "problems"--for GAW15 included information
      from two real data sets and a simulated data set. The first problem utilizing
      real data included gene expression as the phenotype and genome-wide markers for
      linkage and association studies. The second problem allowed for detecting and
      characterizing genetic effects for rheumatoid arthritis. And the simulated
      problem was generated to reflect the data structure underlying the rheumatoid
      arthritis study. Further details on GAW15 are provided here, and the primary
      findings from the workshop are highlighted in the following group summary papers.

PMID- 18046758
TI  - Using linkage and association to identify and model genetic effects: summary of
      GAW15 Group 4.
AB  - Group 4 at Genetic Analysis Workshop 15 focused on methods that exploited both
      linkage and association information to map disease loci. All contributions
      considered the dichotomous trait of rheumatoid arthritis, using either affected
      sibpairs and/or unrelated controls. While one contribution investigated linkage
      and association approaches separately in genome-wide analyses, the remaining
      others focused on joint linkage and association methods in specific genomic
      regions. The latter contributions proposed new methods and/or examined existing
      methods that addressed whether one or more polymorphisms partially or fully
      explained a linkage signal, particularly the methods proposed by Li et al. that
      are implemented in the computer program Linkage and Association Modeling in
      Pedigrees (LAMP). Using simulated SNP data under linkage peaks, several
      contributions found that existing family-based association approaches such as
      those of Martin et al. and Lake et al. had power similar to LAMP and to several
      methods proposed by the contributors for testing that a single nucleotide
      polymorphism partially explains a linkage peak. In evaluating methods for
      identifying if a polymorphism or a set of polymorphisms fully accounted for a
      linkage signal, several contributions found that it was important to understand
      that these methods may be subject to low power in some situations and thus, a non
      significant result was not necessarily indicative of the polymorphism(s) being
      fully responsible for the linkage signal. Finally, modeling the disease using
      association evidence conditional on linkage may improve understanding of the
      etiology of disease.

PMID- 18046759
TI  - Discussing gene-gene interaction: warning--translating equations to English may
      result in jabberwocky.
AB  - Interest in mapping susceptibility alleles for complex diseases, which do not
      follow a classic single-gene segregation pattern, has driven interest in methods
      that account for, or use information from one locus when mapping another. Our
      discussion group examined methods related to epistasis or gene x gene
      interaction. The goal of modeling gene x gene interaction varied across groups;
      some papers tried to detect gene x gene interaction while others tried to exploit
      it to map genes. Most of the 10 papers summarized here applied newly created or
      newly modified statistical methods related to gene x gene interaction, while two
      groups primarily examined computational issues. As is often the case, comparisons
      are complicated by little overlap in the data used across the papers, and further
      complicated by the fact that the available data may not have been ideal for some
      gene x gene interaction methods. However, the main difficulty in comparing and
      contrasting methods across the papers is the lack of a consistent statistical
      definition of gene x gene interaction. But despite these issues, two clear trends
      emerged across the analyses: First, the methods for quantitative trait gene x
      gene interaction appeared to perform very well, even in families initially
      ascertained as affected sib pairs; and second, dichotomous trait gene x gene
      interaction methods failed to produce consistent results. The difficulty of using
      (primarily) affected sib pair data in a gene x gene interaction analysis is
      explored.

PMID- 18046760
TI  - Model selection and Bayesian methods in statistical genetics: summary of group 11
      contributions to Genetic Analysis Workshop 15.
AB  - The research presented in group 11 of the Genetic Analysis Workshop 15 (GAW15)
      falls into two major themes: Model selection approaches for gene mapping (both
      Bayesian and Frequentist); and other Bayesian methods. These methods either allow
      relaxation of some of the common assumptions, such as mode of inheritance, for
      studying complicated genetic systems, or allow incorporation of additional
      information into the model. Over half of the groups applied model selection
      methods on all three data sets, using models in which genetic markers were used
      as predictors for linkage, phenotype expression, or transmission to an affected
      offspring. Most groups employed variations of Stochastic Search Variable
      Selection as the model selection method of choice. A brief review of this class
      of methods is given in this summary paper, followed by highlights of other
      methods and overall summaries of each contribution to the GAW15 presentation
      group 11. These group contributions exhibit the value of framing genetic problems
      in terms of model selection, and highlight the impact of variable selection for
      gene mapping.

PMID- 18046761
TI  - Multiple testing in the genomics era: findings from Genetic Analysis Workshop 15,
      Group 15.
AB  - Recent advances in molecular technologies have resulted in the ability to screen
      hundreds of thousands of single nucleotide polymorphisms and tens of thousands of
      gene expression profiles. While these data have the potential to inform
      investigations into disease etiologies and advance medicine, the question of how
      to adequately control both type I and type II error rates remains. Genetic
      Analysis Workshop 15 datasets provided a unique opportunity for participants to
      evaluate multiple testing strategies applicable to microarray and single
      nucleotide polymorphism data. The Genetic Analysis Workshop 15 multiple testing
      and false discovery rate group (Group 15) investigated three general categories
      for multiple testing corrections, which are summarized in this review:
      statistical independence, error rate adjustment, and data reduction. We show that
      while each approach may have certain advantages, adequate error control is
      largely dependent upon the question under consideration and often requires the
      use of multiple analytic strategies.

PMID- 18046762
TI  - Genome-wide association analyses of expression phenotypes.
AB  - A number of issues arise when analyzing the large amount of data from high
      throughput genotype and expression microarray experiments, including design and
      interpretation of genome-wide association studies of expression phenotypes. These
      issues were considered by contributions submitted to Group 1 of the Genetic
      Analysis Workshop 15 (GAW15), which focused on the association of quantitative
      expression data. These contributions evaluated diverse hypotheses, including
      those relevant to cancer and obesity research, and used various analytic
      techniques, many of which were derived from information theory. Several
      observations from these reports stand out. First, one needs to consider the
      genetic model of the trait of interest and carefully select which single
      nucleotide polymorphisms and individuals are included early in the design stage
      of a study. Second, by targeting specific pathways when analyzing genome-wide
      data, one can generate more interpretable results than agnostic approaches.
      Finally, for datasets with small sample sizes but a large number of features like
      the Genetic Analysis Workshop 15 dataset, machine learning approaches may be more
      practical than traditional parametric approaches.

PMID- 18046763
TI  - Issues in association mapping with high-density SNP data and diverse family
      structures.
AB  - Genetic association studies have the potential to identify causative genetic
      variants with small effects in complex diseases, but it is not at all clear which
      study designs best balance power with sample size, especially when taking into
      account the difficulty of obtaining a sample of the necessary structure. The 14
      contributions from the Genetic Analysis Workshop 15 group 3 used data sets with
      rheumatoid arthritis as primary phenotype from problem 2 (real data) and Problem
      3 (simulated data) to investigate design and analysis problems that arise in
      candidate-gene, candidate-region, and genome-wide association studies. We
      identified three major themes that were addressed by multiple groups: (1)
      comparing family-based and case-control study designs with each other and with
      hybrid designs incorporating both related and unrelated individuals; (2)
      exploring and comparing techniques of combining information from multiple,
      correlated single-nucleotide polymorphisms; and (3) comparing analyses that
      select the model(s) of best fit with the ultimate aim of detecting the joint
      effects of several unlinked single-nucleotide polymorphisms. These contributions
      achieved some success in improving upon existing methods. For example, tests
      using related cases and unrelated controls can achieve higher power than the
      tests using unrelated cases and unrelated controls. Aside from these successes,
      the group 3 contributions highlight some interesting areas for future research.

PMID- 18046764
TI  - Data mining of RNA expression and DNA genotype data: presentation group 5
      contributions to Genetic Analysis Workshop 15.
AB  - The complexity of data available in human genetics continues to grow at an
      explosive rate. With that growth, the challenges to understanding the meaning of
      the underlying information also grow. A currently popular approach to dissecting
      such information falls under the broad category of data mining. This can apply to
      any approach that tries to extract relevant information from large amounts of
      data, but often refers to methods that deal, in a non-linear fashion, with very
      large numbers of variables that cannot be simultaneously handled by more
      conventional statistical methods. To explore the usefulness of some of these
      approaches, 13 groups applied a variety of strategies to the first dataset
      provided to GAW 15 participants. With the extensive microarray and SNP data
      provided for 14 CEPH families, these groups explored multistage analyses, machine
      learning methods, network construction, and other techniques to try to answer
      questions about gene-gene interaction, functional similarities, co-regulated gene
      expression and the mapping of gene expression determinants, among others. In
      general, the methods offered strategies to provide a better understanding of the
      complex pathways involved in gene expression and function. These are still "works
      in progress," often exploratory in nature, but they provide insights into ways in
      which the data might be interpreted. Despite the still preliminary nature of some
      of these methods and the diversity of the approaches, some common themes emerged.
      The collection of papers and methods offer a starting point for further
      exploration of complex interactions in human genetic data now readily available.

PMID- 18046765
TI  - Data mining, neural nets, trees--problems 2 and 3 of Genetic Analysis Workshop
      15.
AB  - Genome-wide association studies using thousands to hundreds of thousands of
      single nucleotide polymorphism (SNP) markers and region-wide association studies
      using a dense panel of SNPs are already in use to identify disease susceptibility
      genes and to predict disease risk in individuals. Because these tasks become
      increasingly important, three different data sets were provided for the Genetic
      Analysis Workshop 15, thus allowing examination of various novel and existing
      data mining methods for both classification and identification of disease
      susceptibility genes, gene by gene or gene by environment interaction. The
      approach most often applied in this presentation group was random forests because
      of its simplicity, elegance, and robustness. It was used for prediction and for
      screening for interesting SNPs in a first step. The logistic tree with unbiased
      selection approach appeared to be an interesting alternative to efficiently
      select interesting SNPs. Machine learning, specifically ensemble methods, might
      be useful as pre-screening tools for large-scale association studies because they
      can be less prone to overfitting, can be less computer processor time intensive,
      can easily include pair-wise and higher-order interactions compared with standard
      statistical approaches and can also have a high capability for classification.
      However, improved implementations that are able to deal with hundreds of
      thousands of SNPs at a time are required.

PMID- 18046766
TI  - Gene by environment interactions.
AB  - This paper summarizes the contributions of group 8 to the Genetic Analysis
      Workshop 15. Group 8 focused on ways to address the possibility that genetic and
      environmental effects on phenotype may not be independent, but instead may
      interact in ways that could play important roles in determining phenotype. Among
      the eight contributors to this group, all three data sets (expression data,
      rheumatoid arthritis data, and simulated data) were analyzed. Contributions to
      this section fell into the two broad categories of refining the data (e.g.
      stratifying or weighting based on a covariate value) and explicitly modeling the
      interactions. The contributions also illustrate that there are at least two
      possible goals for such studies. One goal is simply to identify factors
      contributing to phenotype in the presence of interactions that might mask the
      signal to univariate methods. A related but distinct goal is to characterize an
      interaction (e.g. to determine if the interaction is significant).

PMID- 18046767
TI  - Linkage analyses of rheumatoid arthritis and related quantitative phenotypes: the
      GAW15 experience.
AB  - The group that formed on the theme of linkage analyses of rheumatoid arthritis RA
      and related phenotypes (Group 10) in the Genetic Analysis Workshop 15 comprised
      18 sets of investigators. Two data sets were available: one was a real set
      provided by the North American Rheumatoid Arthritis Consortium and collaborators
      in Canada, France (European Consortium Of Rheumatoid Arthritis Families) and the
      UK; the other was a simulated data set modelled after the real data set. Whereas
      a majority of the investigators analyzed the RA affection status as a binary
      phenotype, a few contributions considered data on correlated quantitative traits
      such as anti-cyclic citrullinated peptide and rheumatoid factor-immunoglobulin M.
      The different investigators applied a wide spectrum of linkage methods. As
      expected, most methods could identify the human leukocyfeantigen region on
      chromosome 6 as a major genetic factor for RA. In addition, some novel
      chromosomal regions provided significant evidence of linkage in multiple
      contributions in the group. In this report, we discuss the different strategies
      explored by the different investigators with the common goal of improving the
      power to detect linkage.

PMID- 18046768
TI  - Multivariate analysis of complex gene expression and clinical phenotypes with
      genetic marker data.
AB  - This paper summarizes contributions to group 12 of the 15th Genetic Analysis
      Workshop. The papers in this group focused on multivariate methods and
      applications for the analysis of molecular data including genotypic data as well
      as gene expression microarray measurements and clinical phenotypes. A range of
      multivariate techniques have been employed to extract signals from the multi
      feature data sets that were provided by the workshop organizers. The methods
      included data reduction techniques such as principal component analysis and
      cluster analysis; latent variable models including structural equations and item
      response modeling; joint multivariate modeling techniques as well as multivariate
      visualization tools. This summary paper categorizes and discusses individual
      contributions with regard to multiple classifications of multivariate methods.
      Given the wide variety in the data considered, the objectives of the analysis and
      the methods applied, direct comparison of the results of the various papers is
      difficult. However, the group was able to make many interesting comparisons and
      parallels between the various approaches. In summary, there was a consensus among
      authors in group 12 that the genetic research community should continue to draw
      experiences from other fields such as statistics, econometrics, chemometrics,
      computer science and linear systems theory.

PMID- 18046770
TI  - Effect of linkage disequilibrium between markers in linkage and association
      analyses.
AB  - Contributions to Group 17 of the Genetic Analysis Workshop 15 considered dense
      markers in linkage disequilibrium (LD) in the context of either linkage or
      association analysis. Three contributions reported on methods for modeling LD or
      selecting a subset of markers in linkage equilibrium to perform linkage analysis.
      When all markers were used without modeling LD, inflated evidence for linkage was
      observed when parental genotypes were missing. All methods for handling LD led to
      some decreased linkage evidence. Two groups performed a genome-wide association
      scan using either mixed models to account for known or unknown relatedness
      between individuals, trend tests or combination statistics. All methods failed to
      detect four of the eight simulated loci because of low LD in some regions. Three
      groups performed association analysis using simulated dense markers on chromosome
      6, where a simulated HLA-DRB1 locus played a major role in disease susceptibility
      along with two additional loci of smaller effect. The overall conditional
      genotype method correctly identified both additional loci while a novel
      transmission disequilibrium test-statistic to combine studies with non
      overlapping markers identified one HLA locus after stratifying on the parental
      HLA-DRB1 genotypes; LD mapping using the Malecot model mapped two loci in this
      region, even when using greatly reduced marker density. While LD between markers
      appears to be a nuisance that may cause spurious linkage results with missing
      parental genotypes in linkage analysis, association analysis thrives on LD, and
      disease genes fail to be detected in regions of low LD.

PMID- 18046769
TI  - Multistage designs in the genomic era: providing balance in complex disease
      studies.
AB  - In this summary paper, we describe the contributions included in the Multistage
      Design group (Group 14) at the Genetic Analysis Workshop 15, which was held
      during November 12-14, 2006. Our group contrasted and compared different
      approaches to reducing complexity in a genetic study through implementation of
      staged designs. Most groups used the simulated dataset (problem 3), which
      provided ample opportunities for evaluating various staged designs. A wide range
      of multistage designs that targeted different aspects of complexity were
      explored. We categorized these approaches as reducing phenotypic complexity,
      model complexity, analytic complexity or genetic complexity. In general we
      learned that: (1) when staged designs are carefully planned and implemented, the
      power loss compared to a single-stage analysis can be minimized and study cost is
      greatly reduced; (2) a joint analysis of the results from each stage is generally
      more powerful than treating the second stage as a replication analysis.

PMID- 18046771
TI  - Genetic association with rheumatoid arthritis-Genetic Analysis Workshop 15:
      summary of contributions from Group 2.
AB  - The papers in presentation group 2 of Genetic Analysis Workshop 15 (GAW15)
      conducted association analyses of rheumatoid arthritis data. The analyses were
      carried out primarily in the data provided by the North American Rheumatoid
      Arthritis Consortium (NARAC). One group conducted analyses in the data provided
      by the Canadian Rheumatoid Arthritis Genetics Study (CRAGS). Analysis strategies
      included genome-wide scans, the examination of candidate genes, and
      investigations of a region of interest on chromosome 18q21. Most authors employed
      relatively new methods, proposed extensions of existing methods, or introduced
      completely novel methods for aspects of association analysis. There were several
      common observations; a group of papers using a variety of methods found stronger
      association, on chromosomes 6 and 18 and in candidate gene PTPN22 among women
      with early onset. Generally, models that considered haplotypes or multiple
      markers showed stronger evidence for association than did single marker analyses.

PMID- 18046772
TI  - Summary of Genetic Analysis Workshop 15: Group 9 linkage analysis of the CEPH
      expression data.
AB  - Group 9 participants carried out linkage analysis of the Centre d'Etude de
      Polymorphism Humain (CEPH) expression data, using strategies that ranged from
      focused investigation of a small number of traits to full genome scans of all
      available traits. Results from five key areas encompass the most important
      results within and across the 17 participating groups. First, both extensive
      genetic heterogeneity and poor predictability of mapping results based on
      heritability have key implications for study design. Second, choice of the map
      used for linkage analysis is influential, with the implication that meiotic maps
      are preferable to physical maps. Third, performance of different analytic methods
      was in general fairly consistent, with the exception of one variance-component
      method that uses marker allele sharing as the dependent rather than independent
      variable. Fourth, multivariate analysis approaches did not generally appear to
      provide advantages over univariate approaches for linkage detection. Finally,
      there were computational and analytic challenges in working with a large public
      data set, along with need for more data documentation.

PMID- 18046773
TI  - The impact of group fissions on genetic structure in Native South America and
      implications for human evolution.
AB  - In a series of publications beginning in the 1960s, Neel and colleagues suggested
      that genetically nonrandom, or "lineal", population fissions contributed to
      genetic structure in ancient human groups. The authors reached this conclusion by
      studying the genetic consequences of village fissions among the Yanomamo, a
      Native South American group thought to have been relatively unaffected by
      European contact and, therefore, representative of the human past. On the basis
      of ethnographic accounts and pedigree data, they further concluded that
      patrilineal relationships were particularly important in shaping the genetic
      structure of villages following fissions. This study reexamines the genetic
      consequences of village fissions using autosomal STRs, Y-chromosome STRs, and
      mitochondrial DNA sequences collected from large samples of individuals from
      multiple Yanomamo villages. Our analyses of the autosomal STRs replicate the
      previous finding that village fissions have produced substantial genetic
      structure among the Yanomamo. However, our analyses of Y-chromosome STRs and
      mtDNA d-loop polymorphisms suggest that other population processes, including
      village movements, inter-village migration, and polygynous marriage, affect
      genetic structure in ways not predicted by a simple model of patrilineal
      fissions. We discuss the broader implications of population fissions for human
      evolution and the suitability of using the Yanomamo as a model for the human
      past.

PMID- 18046774
TI  - Rare mtDNA haplogroups and genetic differences in rich and poor Danish Iron-Age
      villages.
AB  - The Roman Iron-Age (0-400 AD) in Southern Scandinavia was a formative period,
      where the society changed from archaic chiefdoms to a true state formation, and
      the population composition has likely changed in this period due to immigrants
      from Middle Scandinavia. We have analyzed mtDNA from 22 individuals from two
      different types of settlements, Bogebjerggard and Skovgaarde, in Southern
      Denmark. Bogebjerggard (ca. 0 AD) represents the lowest level of free, but poor
      farmers, whereas Skovgaarde 8 km to the east (ca. 200-270 AD) represents the
      highest level of the society. Reproducible results were obtained for 18 subjects
      harboring 17 different haplotypes all compatible (in their character states) with
      the phylogenetic tree drawn from present day populations of Europe. This
      indicates that the South Scandinavian Roman Iron-Age population was as diverse as
      Europeans are today. Several of the haplogroups (R0a, U2, I) observed in
      Bogebjerggard are rare in present day Scandinavians. Most significantly, R0a,
      harbored by a male, is a haplogroup frequent in East Africa and Arabia but
      virtually absent among modern Northern Europeans. We suggest that this subject
      was a soldier or a slave, or a descendant of a female slave, from Roman Legions
      stationed a few hundred kilometers to the south. In contrast, the haplotype
      distribution in the rich Skovgaarde shows similarity to that observed for modern
      Scandinavians, and the Bogebjerggard and Skovgaarde population samples differ
      significantly (P approximately 0.01). Skovgaarde may represent a new upper-class
      formed by migrants from Middle Scandinavia bringing with them Scandinavian
      haplogroups.

PMID- 18046775
TI  - Quantitative three-dimensional shape analysis of the proximal hallucial
      metatarsal articular surface in Homo, Pan, Gorilla, and Hylobates.
AB  - Multidimensional morphometrics is used to compare the proximal articular surface
      of the first metatarsal between Homo, Pan, Gorilla, Hylobates, and the hominin
      fossils A.L. 333-54 (A. afarensis), SKX 5017 (P. robustus), and OH 8 (H.
      habilis). Statistically significant differences in articular surface morphology
      exist between H. sapiens and the apes, and between ape groups. Ape groups are
      characterized by greater surface depth, an obliquely curved articular surface
      through the dorso-lateral and medio-plantar regions, and a wider medio-lateral
      surface relative to the dorso-plantar height. The OH 8 articular surface is
      indistinguishable from H. sapiens, while A.L. 333-54 and SKX 5017 more closely
      resemble the apes. P. robustus and A. afarensis exhibit ape-like oblique
      curvature of the articular surface.

PMID- 18046776
TI  - Brief communication: Comparison of methods for estimating chronological age at
      linear enamel formation on anterior dentition.
AB  - Linear enamel hypoplasia (LEH) is an enamel defect that records the effects of
      physiological stress on tooth formation. Estimating the age at which LEH defects
      form is integral to the reconstruction of population health in bioarcheological
      studies. Two principal methods for aging LEH defects have been introduced in the
      literature. The conventional approach employs regression equations based on a
      linear model of tooth growth. The newer, Reid and Dean [Am J Phys Anthropol 113
      (2000) 135-139] approach, is based upon a histologically derived curvilinear
      model of enamel development and therefore likely provides more accurate age
      estimates. However, the extent to which the Reid and Dean method produces
      estimated ages at defect formation differing from those of the regression
      equations has not, until now, been determined. This study quantifies the
      differences between these two methods. Evaluating the degree to which these
      methods differ is essential for interpreting the accuracy of LEH age estimates
      given in previous bioarcheological studies. Age estimates of LEH defects on 338
      anterior teeth from the Hamann-Todd osteological sample were calculated using
      both methods. The resulting estimated ages were compared through a randomized
      block ANOVA. However, the mean differences between the estimated ages yielded by
      both methods range from 4 months or less depending on the tooth type with an
      overall average of 2.63 months. The discussion focuses on the degree to which
      this difference affects answers to bioarcheological questions.

PMID- 18046777
TI  - Seasonal changes in household food insecurity and symptoms of anxiety and
      depression.
AB  - There is growing awareness that common mental health disorders are key
      contributors to the burden of disease in developing countries. Studies examining
      the correlates of mental health have primarily been carried out in urban settings
      and focused on the burden rapid economic change places on individuals. In these
      settings, poverty and low education are consistent predictors of anxiety and
      depressive symptoms. We argue here that these variables are proxies for
      insecurity, and that a more general model of symptoms of depression and anxiety
      should focus on locally salient forms of insecurity. Building on previous work in
      a seasonal subsistence setting, we identify food insecurity as a potent source of
      insecurity in a rural African setting, and then test whether seasonal changes in
      food insecurity are correlated with concomitant changes in a measure of symptoms
      of anxiety and depression among 173 caretakers. Results indicate that food
      insecurity is a strong predictor of symptoms of anxiety and depression (P <
      0.0001), that changes in food insecurity across the seasons predict changes in
      symptoms of anxiety and depression (P < 0.0001), and that this is robust to the
      inclusion of covariates for material assets and household production. These
      results hold for individuals in both ethnic groups studied (Pimbwe and Sukuma);
      however, at the group level the burden falls disproportionately on Pimbwe. The
      results add to the growing literature on the causes of population level
      differences in mental health disorders and suggest new research avenues and
      strategies to link mental health disorders with variation in physical and
      biosocial outcomes.

PMID- 18046778
TI  - Diet and reproductive function in wild female chimpanzees (Pan troglodytes
      schweinfurthii) at Kibale National Park, Uganda.
AB  - Human female reproductive function is highly sensitive to current energetic
      condition, indicating adaptation to modulate reproductive effort in accordance
      with changing ecological conditions that might favor or disfavor the production
      of offspring. Here, we test the hypothesis that reproductive capacity in female
      chimpanzees is likewise limited by current energetic condition. We used 12 years
      of data on wild chimpanzees (Pan troglodytes schweinfurthii) in the Kanyawara
      community of Kibale National Park, Uganda, to examine the relationship of dietary
      quality, as assessed by fruit components of the diet, to the occurrence of
      sexually receptive females, concentrations of ovarian steroid hormones, and
      timing of conception. We found that the frequency of females having sexual
      swellings was positively related to the consumption of drupe fruits. Estrogen
      levels of both cycling and noncycling females increased during seasonal peaks in
      the consumption of drupe fruits. When average fruit consumption remained high
      across months, females conceived more quickly. These results support the
      hypothesis that cycling and conception in chimpanzees are contingent upon high
      energy balance, and they indicate that the availability of fruit is a key
      variable limiting reproductive performance in chimpanzees. Chimpanzees appear to
      share with humans a reproductive system that is primed to respond to proximate
      levels of energy acquisition.

PMID- 18046779
TI  - Evolutionary changes in the masticatory complex following the transition to
      farming in the southern Levant.
AB  - A post-Pleistocene reduction trend in the dimensions of the masticatory complex
      followed the transition to agricultural lifestyle in several world regions. A
      major limitation of previous studies is large temporal gaps between the analyzed
      skeletal populations, which do not allow the detection and analysis of a
      diachronic morphological transition. In this work, we analyze a large number of
      specimens from the southern Levant, where agriculture first emerged in situ and
      for which there is a good diachronic sequence of the shift from a hunting
      gathering way of life to a food producing, farming economy (12,000-7,000
      uncalibrated bp). Changes in the masticatory complex are examined in the context
      of three prevailing dental reduction models: the Probable Mutation Effect
      (Brace,1963; Brace and Mahler,1971), Increasing Population Density Effect
      (Macchiarelli and Bondioli,1986) and Selective Compromise Effect (SCE)
      (Calcagno,1989). A series of linear regressions of dimension vs. time and
      coefficients of variation for each dimension are analyzed. Our results indicate
      significant reduction in the buccolingual but not mesiodistal dental dimensions
      and in the ramus breadth and anterior height dimensions of the mandible but not
      in its overall size. These findings, taken together with low coefficients of
      variation for the buccolingual dimensions, suggest selective pressure resulting
      in reduction of specific dimensions. The observed trend is in partial accordance
      with the SCE but differs from the trends observed in other regions, and is
      therefore best explained as a region-specific variant of the SCE.

PMID- 18046780
TI  - The Hellenic Heart Foundation. Interview by Robert Short.

PMID- 18046782
TI  - Healthy diet, healthy heart, healthy prostate.

PMID- 18046781
TI  - Management of atrial fibrillation.

PMID- 18046783
TI  - Resolved: in minimizing kidney transplant immunosuppression, steroids should go
      before calcineurin inhibitors: con.

PMID- 18046784
TI  - A critical review of fear tests used on cattle, pigs, sheep, poultry and horses.
AB  - Fear is arguably the most commonly investigated emotion in domestic animals. In
      the current review we attempt to establish the level of repeatability and
      validity found for fear tests used on cattle, pigs, sheep and goats, poultry and
      horses. We focus the review on the three most common types of fear tests: the
      arena test (open field), the novel object test, and the restraint test. For some
      tests, e.g. tonic immobility in poultry, there is a good and broad literature on
      factors that affect the outcome of the test, the validity of the test and its age
      dependency. However, there are comparatively few of these well defined and
      validated tests and what is especially missing for most tests is information on
      the robustness, i.e., what aspects can be changed without affecting the validity
      of the tests. The relative absence of standardized tests hampers the development
      of applied ethology as a science.

PMID- 18046786
TI  - Obesity, mortality, and bariatric surgery death rates.

PMID- 18046787
TI  - Commentary: methods to increase response rates to postal questionnaires.

PMID- 18046788
TI  - [A man with viral myocarditis].

PMID- 18046789
TI  - [Time for specific diagnostics?].

PMID- 18046790
TI  - [Mosquito nets save children's lives].

PMID- 18046791
TI  - [Extracorporeal elimination].

PMID- 18046795
TI  - And so we model: the ineffective use of mathematical models in ecological risk
      assessments.

PMID- 18046796
TI  - Design and application of a transparent and scalable weight-of-evidence
      framework: an example from Wabamun Lake, Alberta, Canada.
AB  - A weight-of-evidence (WOE) framework was developed to evaluate potential effects
      on the aquatic ecosystem of Wabamun Lake (Alberta, Canada) associated with the
      release of Bunker "C" oil after a train derailment. The wide variety of
      stakeholders and interested regulatory agencies made it necessary to develop a
      consistent and transparent approach to assessing ecological effects on multiple
      ecosystem components within the lake with the use of a large number of lines of
      evidence (LOEs). Consequently, a scalable WOE framework was necessary to
      integrate the findings of 38 different LOEs. A priori and a posteriori weighting
      factors were applied to each individual LOE, and a combination of numeric and
      nonnumeric rating systems was used to integrate LOEs into an overall WOE
      conclusion for 5 different ecosystem components. We provide guidance regarding
      the development of a WOE framework and emphasize techniques that enhance the
      application of best professional judgement during the WOE process.

PMID- 18046797
TI  - Effect of sediment remediation on polychlorinated biphenyl concentrations in
      tomatoes grown near New Bedford Harbor.
AB  - Measurements of polychlorinated biphenyl (PCB) congener concentrations and
      profiles from produce grown near New Bedford Harbor, Massachusetts, USA, before,
      during, and after remediation of PCB-contaminated sediment are presented. Samples
      of tomatoes collected from locations upwind and downwind relative to harbor
      contamination are compared with the use of measurements of 47 individual PCB
      congeners. The PCB concentration in the locally grown tomatoes, as expressed by
      the sum of congeners, is highest during the period of harbor dredging and drops
      to its lowest point after remediation, which included dredging and excavation.
      The downwind location is characterized by higher concentrations of PCBs than the
      upwind location in every time period. Principal component analysis is used to
      distinguish both the effect of remediation over time and the effect of
      cultivation location on the congener profiles. Evidence of the PCB congener
      profile representing the contaminated harbor sediments is strongest during the
      dredging period and in the downwind location. These results have important
      implications for understanding human exposure via the food chain and highlight
      the importance of considering exposure pathways related to atmospheric transport
      during remediation of contaminated sediments.

PMID- 18046798
TI  - Evaluating consistency of best professional judgment in the application of a
      multiple lines of evidence sediment quality triad.
AB  - The bioavailability of sediment-associated contaminants is poorly understood.
      Often, a triad of chemical concentration measurements, laboratory sediment
      toxicity tests, and benthic infaunal community condition is used to assess
      whether contaminants are present at levels of ecological concern. Integration of
      these 3 lines of evidence is typically based on best professional judgment by
      experts; however, the level of consistency among expert approach and
      interpretation has not been determined. In this study, we compared the
      assessments of 6 experts who were independently provided data from 25 California
      embayment sites and asked to rank the relative condition of each site from best
      to worst. The experts were also asked to place each site into 1 of 6
      predetermined categories of absolute condition. We provided no guidance regarding
      assessment approach or interpretation of supplied data. The relative ranking of
      the sites was highly correlated among the experts, with an average correlation
      coefficient of 0.92. Although the experts' relative rankings were highly
      correlated, the categorical assessments were much less consistent, with only 1
      site out of 25 assigned to the same absolute condition category by all 6 experts.
      Most of the observed categorical differences were small in magnitude and involved
      the weighing of different lines of evidence in individual assessment approaches,
      rather than interpretation of signals within a line of evidence. We attribute
      categorical differences to the experts' use of individual best professional
      judgment and consider these differences to be indicative of potential uncertainty
      in the evaluation of sediment quality. The results of our study suggest that
      specifying key aspects of the assessment approach a priori and aligning the
      approach to the study objectives can reduce this uncertainty.

PMID- 18046799
TI  - Incorporating results of avian toxicity tests into a model of annual reproductive
      success.
AB  - Modeling the effects of pesticide exposure on avian populations requires
      knowledge of how the pesticide changes survival and fecundity rates for the
      population. Although avian reproduction tests are the primary source of
      information on reproductive effects in the pesticide risk assessment process,
      current tests cannot provide a direct estimate of the effects of a pesticide on
      fecundity rates. We present a mathematical model that integrates information on
      specific types of effects from reproduction tests with information on avian life
      history parameters, the timing of pesticide applications, and the temporal
      pattern of pesticide exposure levels to estimate pesticide effects on annual
      reproductive success. The model demonstration follows nesting success of females
      in no-pesticide or pesticide-exposed populations through a breeding season to
      estimate the mean number of successful broods per female. We demonstrate the
      model by simulating populations of a songbird exposed to 1 of 2 hypothetical
      pesticides during a breeding season. Finally, we discuss several issues for
      improving the quantitative estimation of annual reproductive success.

PMID- 18046800
TI  - Development and evaluation of an aquatic ecological risk assessment system
      (KORECORisk) for the management of industrial complexes.
AB  - KORea ECOlogical Risk assessment (KORECORisk) was developed to support decision
      making for the ecological risk-based management of chemicals in industrial
      complexes in South Korea. The system is based on a geographical information
      system and consists of a release rate estimation module, an exposure estimation
      module, and an ecological risk assessment module. For release rate and exposure
      estimation, the chemical use data from the national chemical inventory database
      and a dynamic multimedia fate model, respectively, were used. The ecological risk
      was assessed by calculating the risk quotient. A case study was presented to
      demonstrate an application of KORECORisk to setting a risk-based priority among
      the 6 major industrial complexes or among the chemicals used in the individual
      industrial complexes. Furthermore, a more detailed assessment was performed to
      demonstrate and evaluate a potential use of KORECORisk for the management of
      individual complexes. With 3 phthalates (1,2-benzenedicarboxylic acid dibutyl
      ester; 1,2-benzenedicarboxylic acid dimethyl ester; and 1,2-dibenzenedicarboxylic
      acid dioctyl ester) as model chemicals, KORECORisk provided prediction in time
      and space that are of sufficient resolution required for the aquatic risk
      assessment but with varying uncertainty. The uncertainty associated with the use
      of KORECORisk appeared to vary widely (from <10 to 10(3)) with the chemical.
      Within the range of the chemicals tested, the release rate estimation appeared to
      introduce larger uncertainty than the exposure estimation. A more accurate
      chemical use inventory would improve the accuracy of not only the chemical
      release estimation but the exposure estimation module by reducing the influence
      of the unidentified sources. The release estimation module should be modified to
      provide temporal variation with a time resolution relevant to the exposure
      duration for which toxic effects could occur.

PMID- 18046801
TI  - Application of the biotic ligand model for regulatory purposes to selected rivers
      in Argentina with extreme water-quality characteristics.
AB  - The biotic ligand model (BLM) was used to assess copper (Cu) bioavailability,
      toxicity, water-effect ratios (WER), and Cu site-specific water-quality criteria
      (SSWQC) in the Matanza River and Pilcomayo River, Argentina, where anthropogenic
      inputs and natural phenomena have led to high concentrations of chemical species
      capable of reducing metal toxicity: Sodium, total hardness, alkalinity, dissolved
      organic carbon, and suspended particulate matter (SPM), as well as other metals.
      The purpose of this study was to evaluate the feasibility of developing Cu-SSWQC
      from a modified scenario of the BLM-Monte-Carlo method model. The response of the
      BLM model in these rivers, with water quality near its application boundary
      conditions, was evaluated during the 2003 to 2004 hydrological cycle. Cu toxicity
      tests were conducted with Daphnia magna as the test organism. The BLM (Version
      ap08) toxicity estimates for D. magna were within a factor of 2 of the line of
      perfect agreement with toxicity test results, although highly variable relevant
      water-quality parameters showed that mean estimates were more than 2 times the
      mean 50% effective concentration (EC50) derived from the corresponding toxicity
      tests. Suspended particulate matter was an important sink for Cu added to
      unfiltered water of the Pilcomayo River, but it also exerted some toxic effect.
      Minimums WER, estimated with a modified scenario of the BLM-MONTE, ranged from
      1.5 (Pilcomayo River, at Mision La Paz) up to 11 (Matanza River, at Route 3). The
      corresponding Cu-SSWQC values were 30 and 105 microg/L, respectively.

PMID- 18046802
TI  - Sediment quality assessment and dredged material management in Spain: Part I,
      application of sediment quality guidelines in the Bay of Santander.
AB  - Sediments are an essential component of aquatic ecosystems that must be assessed
      and managed properly. The use of quantitative environmental quality standards
      derived from consideration of sediment quality guidelines (SQGs) can be effective
      as part of a tiered risk assessment approach. In Part I of this 2-part paper
      addressing sediment quality assessment and dredged material management in Spain,
      different SQG methods are used to evaluate sediment quality in the Bay of
      Santander, located in the Cantabric Sea along the northern coast of Spain, and to
      guide development of empirically derived SQGs for marine sediments. The results
      of the study indicate a great heterogeneity of SQGs, both with regard to the
      numeric values for a particular chemical and the number of substances for which
      SQGs have been derived. The analysis highlights the scarce development of
      empirical SQGs for priority substances identified in current European Union water
      policy. Nonetheless, the application of SQGs makes it possible to classify
      different zones of sediment quality in the Bay of Santander. Part II of this 2
      part paper considers the environmental impacts of dredged material disposal.
      Legislation and criteria used to regulate dredged material disposal at sea in
      different European countries are reviewed, and action levels derived by different
      countries were used to evaluate management of dredged sediments from Cadiz Bay,
      located on the South Atlantic coast of Spain.

PMID- 18046803
TI  - Sediment quality assessment and dredged material management in Spain: Part II,
      analysis of action levels for dredged material management and application to the
      Bay of Cadiz.
AB  - When sediments are removed from aquatic bottoms, they turn into dredged material
      that must be managed, taking into account its environmental impact. In Part II of
      this 2-part paper addressing sediment quality assessment and dredged material
      management in Spain, legislation and criteria used to regulate dredged material
      disposal at sea in different European countries are reviewed, as are action
      levels (ALs) derived by different countries used to evaluate management of
      dredged sediments from Cadiz Bay located on the South Atlantic coast of Spain.
      Comparison of ALs established for dredged material disposal by different
      countries reveals orders of magnitude differences in the values established for
      the same chemical. In Part I of this 2-part paper, review of different sediment
      quality guideline (SQG) methods used to support sediment quality assessments
      indicated a great heterogeneity of SQGs, both with regard to the numeric values
      for a particular chemical and the number of substances for which SQGs have been
      derived. The analysis highlighted the absence of SQGs for priority substances
      identified in current European Union water policy. Here, in Part II, the ALs are
      applied to dredged sediments from Cadiz Bay (South Atlantic coast of Spain),
      evidencing that the heterogeneity of ALs implemented in the reviewed countries
      could determine different management strategies. The application of other
      measurements such as bioassays might offer information useful in identifying a
      cost-effective management option in a decision-making framework, especially for
      dredged material with intermediate chemical concentrations.

PMID- 18046804
TI  - Technical issues affecting the implementation of US Environmental Protection
      Agency's proposed fish tissue-based aquatic criterion for selenium.
AB  - The US Environmental Protection Agency is developing a national water quality
      criterion for selenium that is based on concentrations of the element in fish
      tissue. Although this approach offers advantages over the current water-based
      regulations, it also presents new challenges with respect to implementation. A
      comprehensive protocol that answers the "what, where, and when" is essential with
      the new tissue-based approach in order to ensure proper acquisition of data that
      apply to the criterion. Dischargers will need to understand selenium transport,
      cycling, and bioaccumulation in order to effectively monitor for the criterion
      and, if necessary, develop site-specific standards. This paper discusses 11 key
      issues that affect the implementation of a tissue-based criterion, ranging from
      the selection of fish species to the importance of hydrological units in the
      sampling design. It also outlines a strategy that incorporates both water column
      and tissue-based approaches. A national generic safety-net water criterion could
      be combined with a fish tissue-based criterion for site-specific implementation.
      For the majority of waters nationwide, National Pollution Discharge Elimination
      System permitting and other activities associated with the Clean Water Act could
      continue without the increased expense of sampling and interpreting biological
      materials. Dischargers would do biotic sampling intermittently (not a routine
      monitoring burden) on fish tissue relative to the fish tissue criterion. Only
      when the fish tissue criterion is exceeded would a full site-specific analysis
      including development of intermedia translation factors be necessary.

PMID- 18046805
TI  - Microplastic--an emerging contaminant of potential concern?

PMID- 18046806
TI  - A call for scientific rigor in the development of critical body residues: a case
      study.

PMID- 18046807
TI  - Toxicogenomic assessment of the population level impacts of contaminants.

PMID- 18046808
TI  - Assessments of cumulative ecological effects of agricultural stressors on aquatic
      communities: an elaboration of the sediment quality triad.

PMID- 18046810
TI  - Aids for implementing new AHA antibiotic prophylaxis guidelines.

PMID- 18046809
TI  - Hospital and MDs form company for managing surgical services.

PMID- 18046811
TI  - Weight loss. Keeping it off.

PMID- 18046812
TI  - Planning ahead for sick days. Just when you're feeling your worst is when it's
      most important to stay vigilant about your diabetes care.

PMID- 18046814
TI  - Avoiding complications. Nuturing your "health bank".

PMID- 18046813
TI  - Late summer recipes.

PMID- 18046815
TI  - The pressure is on. Hypertension and diabetes.

PMID- 18046816
TI  - For parents. When your child needs surgery.

PMID- 18046817
TI  - Diabetes quiz. How much do you know about the effect of diet on cholesterol?

PMID- 18046818
TI  - Supermarket smarts. Cooking oils.

PMID- 18046819
TI  - Diabetes resources. Pump resources.

PMID- 18046820
TI  - Thyroid disorders and diabetes. It is common for a person to be affected by both
      thyroid disease and diabetes.

PMID- 18046821
TI  - Diabetic peripheral neuropathy.

PMID- 18046822
TI  - China's problem, the world's challenge.

PMID- 18046823
TI  - A trimmer you. The right choices. How to keep those holiday pounds at bay.

PMID- 18046825
TI  - The effect of diabetes. A snapshot of a crisis.

PMID- 18046824
TI  - Time for yourself. Should you add massage to your regimen?

PMID- 18046826
TI  - Powder days. Skiing is a lifelong passion for Jim Stokes.

PMID- 18046827
TI  - A world of flavor.

PMID- 18046828
TI  - The American revolution. Flavor takes charge in this healthy and delicious twist
      on the traditional holiday meal.

PMID- 18046830
TI  - Research profile. A tricky business. Control may be key to kidney transplant
      success. Kathie Lynn Hermayer, MD, MS.

PMID- 18046829
TI  - Brunch Italian style.

PMID- 18046831
TI  - An historic turning point arrives for HIV therapy.

PMID- 18046832
TI  - Shape-shifting: the art of drug pricing.

PMID- 18046833
TI  - Update on experimental antiretrovirals.

PMID- 18046834
TI  - Flu shots and the upcoming flu season.

PMID- 18046835
TI  - Reyataz monotherapy study stopped.

PMID- 18046836
TI  - Dutch study finds treatment interruptions safe for some.

PMID- 18046837
TI  - Which bronchodilator in COPD?

PMID- 18046838
TI  - ESBRA 2007. Abstracts of the 11th Congress of the European Society for Biomedical
      Research on Alcoholism, 23-26 September, Berlin, Germany.

PMID- 18046839
TI  - No cause for alarm.

PMID- 18046840
TI  - Disability studies: the old and the new.

PMID- 18046841
TI  - The immaculate ovum: Jonathan Edwards and the construction of the female body.

PMID- 18046842
TI  - Abstracts of the 12th World Congress on Advances in Oncology and the 10
      International Symposium on Molecular Medicine, 11-13 October 2007, Hersonissos,
      Crete, Greece.

PMID- 18046843
TI  - Abstracts of the 3rd Asian Chapter Meeting of the International Society for
      Peritoneal Dialysis, November 22-24, 2007, Hiroshima, Japan.

PMID- 18046844
TI  - Bibliography. Current world literature. Andrology, sexual dysfunction and
      infertility.

PMID- 18046845
TI  - Abstracts of the 1st Pan-American Congress of Atherosclerosis, August 9-11, 2007,
      Sao Paulo, Brazil.

PMID- 18046846
TI  - Mystical pregnancy and holy bleeding: visionary experience in Early Modern
      Britain and America.

PMID- 18046847
TI  - [A nine-year-old girl with a blue eye].
AB  - We present a nine-year-old girl with fracture of the orbital floor and herniation
      of soft tissue and extraocular musculature into the maxillary sinus. A marked
      restriction of upward gaze was noted. Surgery was performed after two days.
      Herniated tissue was released and the orbital floor reconstructed. One week later
      she had normal eye motility. Orbital fractures of children are rare, but we
      stress the importance of careful clinical examination and early surgery. Due to
      the elasticity of the bone and lack of periorbital fat in children, extraocular
      musculature is more prone to entrapment in the orbital floor. The most important
      sign is limitation of gaze upwards. CT findings are of less importance. Early
      surgical management within 24 - 48 hours will reduce the risk of necrosis and
      fibrosis of extraocular musculature resulting in reduced eye motility.

PMID- 18046848
TI  - [Facial fractures in children].

PMID- 18046849
TI  - Sheets of a pleasant colour.

PMID- 18046850
TI  - The temper thing.
AB  - Examines the tempers and uses of anger by various U.S. presidents, including
      Andrew Jackson, Theodore Roosevelt, Harry Truman, Richard Nixon, and Lyndon
      Johnson.

PMID- 18046852
TI  - [Abstracts of the French Radiology Meeting (JFR), 20-24 October 2007, Paris,
      France].

PMID- 18046851
TI  - [Abstracts of the 51st Annual Meeting of the Japanese Society  for Medical
      Mycology, November 9-10, 2007, Gifu, Japan].

PMID- 18046853
TI  - Microscopy Conference 2007. Proceedings of the 33rd Conference of the German
      Society of Electron Microscopy, September 2-7, 2007, Saarbrucken, Germany.

PMID- 18046854
TI  - Weak legs: misbehavior before the enemy.

PMID- 18046855
TI  - Inorganic arsenic in drinking water and bladder cancer: a meta-analysis for dose
      response assessment.

PMID- 18046856
TI  - International Zinc Nutrition Consultative Group (IZiNCG) technical document #1.
      Assessment of the risk of zinc deficiency in populations and options for its
      control.

PMID- 18046857
TI  - The benefits of combined treatment with corticosteroids and long-acting beta
      agonists.

PMID- 18046858
TI  - The severity of airways obstruction as a determinant of treatment response in
      COPD.
AB  - Guidelines recommend that patients with COPD are stratified arbitrarily by
      baseline severity (FEV1) to decide when to initiate combination treatment with a
      long-acting beta2-agonist and an inhaled corticosteroid. Assessment of baseline
      FEV1 as a continuous variable may provide a more reliable prediction of treatment
      effects. Patients from a 1-year, parallel-group, randomized controlled trial
      comparing 50 microg salmeterol (Sal), 500 microg fluticasone propionate (FP), the
      combination (Sal/FP) and placebo, (bid), were categorized post hoc into FEV1 <
      50% and FEV1 > or = 50% predicted subgroups (n = 949/513 respectively). Treatment
      effects on clinical outcomes-- lung function, exacerbations, health status, diary
      card symptoms, and adverse events--were investigated. Treatment responses based
      on a pre-specified analysis explored treatment differences by severity as a
      continuous variable. Lung function improved with active treatment irrespective of
      FEV1; Sal/FP had greatest effect. This improvement appeared additive in milder
      disease; synergistic in severe disease. Active therapy significantly reduced
      exacerbation rate in patients with FEV1 < 50% predicted, not in milder disease.
      Health status and breathlessness improved with Sal/FP irrespective of baseline
      FEV1; adverse events were similar across subgroups. The spirometric response to
      Sal/FP varied with baseline FEV1, and clinical benefits were not restricted to
      patients with severe disease. These data have implications for COPD management
      decisions, suggesting that arbitrary stratifications of baseline severity are not
      necessarily indicative of treatment efficacy and that the benefits of assessing
      baseline severity as a continuous variable should be assessed in future trials.

PMID- 18046859
TI  - Changing the burden of COPD mortality.
AB  - COPD is a major cause of mortality and morbidity worldwide with an estimated 2.75
      million deaths in 2000 (fourth leading cause of death). In addition to the
      considerable morbidity and mortality associated with COPD, this disease incurs
      significant healthcare and societal costs. Current COPD guidelines acknowledge
      that the following can improve COPD mortality: smoking cessation; long-term
      oxygen therapy; and lung volume reduction surgery in small subsets of COPD
      patients. To date, no randomized controlled trials have demonstrated an effect of
      pharmacological treatment on mortality, although several observational studies
      suggest that both long-acting bronchodilators and inhaled corticosteroids may
      provide a survival benefit. The possibility that these treatments reduce
      mortality is being investigated in ongoing large-scale clinical trials.

PMID- 18046860
TI  - Salmeterol/fluticasone combination in the treatment of COPD.
AB  - Clinical trials of a combination therapy of an inhaled corticosteroid,
      fluticasone propionate (FP), with a long-acting beta2-agonist, salmeterol (Sal),
      have demonstrated a greater improvement in lung function and in quality of life
      measures after the combination compared with either component of alone. In a
      subanalysis of the data of the TRISTAN study, Sal/FP reduced exacerbation rates
      in COPD patients with a baseline FEV1 < 50% of predicted. A combination therapy
      of budesonide and formoterol improved quality of life and FEV1, and reduced
      exacerbations better than either component alone. In studies of FP or of Sal/FP
      in COPD, there was a reduction in all-cause mortality by 25% relative to placebo.
      Sal/FP has anti-inflammatory effects in COPD airways. FP inhibits markers of
      systemic inflammation, and it is not known whether Sal/FP has an advantage over
      FP alone. While long-acting beta2-agonists such as Sal can be recommended for
      treatment of moderate COPD, addition of inhaled steroid therapy such as FP should
      be considered in more severe disease.

PMID- 18046861
TI  - Newer fluoroquinolones in the treatment of acute exacerbations of COPD.
AB  - Acute exacerbations of COPD are a major cause of morbidity and mortality.
      Bacteria are implicated in about half of all cases. The frequency of
      exacerbations is related to decline in lung function and poorer quality of life.
      25% of patients with COPD have bacterial colonization of the lower airways in
      stable state whereas non-smokers without COPD have airways that are sterile. The
      significance of the colonization is unclear, but there is emerging evidence that
      it may be detrimental. Much of the data recommending antibiotic treatment are
      based on findings more than 10 years old and do not take into account emerging
      bacterial resistance. This article reviews these data and that from newer
      antibiotic trials. It also reviews current antibiotic prescribing guidelines from
      major respiratory societies around the world. Recent antibiotic trials have
      compared fluoroquinolones with "standard" antibiotics and found, in the main,
      longer exacerbation-free intervals and better bacterial eradication rates in
      those treated with fluoroquinolones.

PMID- 18046862
TI  - Use of Respimat Soft Mist inhaler in COPD patients.
AB  - Events of the past decade have stimulated development of new drug formulations
      and delivery devices that have improved the efficiency, ease of use, and
      environmental impact of inhaled drug therapy. Respimat Soft Mist Inhaler is a
      novel, multidose, propellant-free, hand-held, liquid inhaler that represents a
      new category of inhaler devices. The aerosol cloud generated by Respimat contains
      a higher fraction of fine particles than most pressurized metered dose inhalers
      (pMDIs) and dry powder inhalers (DPIs), and the aerosol spray exits the inhaler
      more slowly and for a longer duration than with pMDIs. This translates into
      higher lung drug deposition and lower oropharyngeal deposition, making it
      possible to give lower nominal doses of delivered drugs without lowering
      efficacy. In clinical trials in patients with COPD, bronchodilator drugs
      delivered from Respimat were equally effective at half of the dose delivered from
      a pMDI. In one study of inhaler preference, Respimat was preferred over the pMDI
      by patients with COPD and other obstructive lung diseases. Respimat is a valuable
      addition to the range of inhaler devices available to the patient with COPD.

PMID- 18046863
TI  - A meta-analysis on the efficacy of oral theophylline in patients with stable
      COPD.
AB  - BACKGROUND: Theophylline is a nonspecific inhibitor of phosphodiesterases that,
      despite exerting bronchodilator and anti-inflammatory effects, is a third-line
      therapy rarely used to treat chronic airflow limitation. We wished to evaluate
      the efficacy of oral theophylline as measured by improvements in trough (pre
      dose) or peak (post-dose) FEV1 and FVC in patients with clinically stable COPD.
      DESIGN: Meta-analysis of randomized, placebo-controlled trials reported as of
      June 2005 in which theophylline was orally administered to stable COPD patients
      and the functional evaluations included pre- and post-theophylline values for
      FEV1 and FVC. RESULTS: Atotal of 18 trials were included in the meta-analysis.
      The weighted mean differences (WMD) with 95% confidence intervals (95% CI) for
      improvement over placebo in trough FEV1 and FVC were 0.108L (0.053-0.163) and
      0.186L (0.036-0.336), respectively, while peak FEV1 and FVC improved by 0.096L
      (0.044-0.147) and 0.242L (0.11-0.374), respectively. CONCLUSIONS: Treatment with
      oral theophylline improves both trough and peak FEV1 and FVC in clinically stable
      COPD patients. These results support previously reported benefits of theophylline
      in COPD.

PMID- 18046864
TI  - Genotypes in matrix metalloproteinase 9 are a risk factor for COPD.
AB  - A growing body of evidence indicates that matrix metalloproteinases (MMPs) play a
      role in the pathogenesis of COPD. Therefore, we conducted a candidate gene
      association study of 4 promoter polymorphisms that are known to modify expression
      levels of the MMP-1, MMP-2, and MMP-9 genes and a Gln279Arg polymorphism in exon
      6 of MMP-9 that modifies the substrate-binding region. We examined the
      association of each variant and haplotypes in 385 male veterans with greater than
      20 pack-years of cigarette smoking whose COPD status was characterized using
      spirometry. The association of these polymorphisms was also examined with decline
      of pulmonary function in a subset of participants. Only the 279Arg variant was
      more common in participants with COPD and the homozygous variant was associated
      with a 3-fold increased risk for COPD. In the haplotype analysis, the haplotype
      comprising the 249Arg and the CA promoter polymorphism within the MMP-9 gene was
      associated with risk, suggesting that either 279Arg or a linked variant on this
      haplotype underlies the association. No association of this polymorphism was
      found with decline in pulmonary function. These studies show that variants of the
      MMP-9 gene are associated with COPD in this cohort of veterans.

PMID- 18046865
TI  - Cost-effectiveness of smoking cessation and the implications for COPD.
AB  - The cost burden of COPD is substantial for patients and families, payers, and
      society as a whole. Smoking has been known for decades to be the leading cause of
      the disease. Numerous studies have been completed to address the cost
      effectiveness of programs created to aid smokers in their efforts to quit.
      Because several assumptions must be made in order to conduct such a study, and
      because differences in study design are numerous, comparison of data is
      difficult. However, studies have consistently shown that regardless of the
      perspective from which the study was completed, or the methods used to help
      smokers abstain, the interventions are cost-effective. Although no study has been
      conducted specifically to assess the cost-effectiveness of smoking cessation
      interventions as they relate directly to patients with COPD, based on current
      data it can be concluded that smoking cessation programs are cost-effective for
      this population.

PMID- 18046867
TI  - Cough and its importance in COPD.
AB  - Patients with COPD most frequently complain of breathlessness and cough and these
      are both increased during exacerbations. Studies have generally focused on
      quality of life during end-stage disease, where breathlessness becomes dominant
      and cough less important. There are very little data on the frequency and
      severity of cough in COPD or its impact on quality of life at different stages of
      disease. Little is known about the factors that influence objective cough counts
      in COPD. Cough may be a marker for progressive disease in milder COPD patients
      who continue to smoke, and it may be useful in case-finding for milder disease in
      the community.The cough reflex sensitivity is heightened in COPD compared with
      healthy volunteers and similar to that in subjects with asthma. The degree of
      airflow obstruction does not predict cough reflex sensitivity or objective cough
      counts, implying an independent process. Effective treatments for cough in COPD
      have not yet been identified. Improved outcome measures of cough, a better
      understanding of cough in the natural history of COPD, and its importance to
      patients are needed.

PMID- 18046866
TI  - Palliative management of refractory dyspnea in COPD.
AB  - COPD is a progressive illness with worldwide impact. Patients invariably reach a
      point at which they require palliative interventions. Dyspnea is the most
      distressing symptom experienced by these patients; when not relieved by
      traditional COPD management strategies it is termed "refractory dyspnea" and
      palliative approaches are required. The focus of care shifts from prolonging
      survival to reducing symptoms, increasing function, and improving quality of
      life. Numerous pharmacological and non-pharmacological interventions can achieve
      these goals, though evidence supporting their use is variable. This review
      provides a summary of the options for the management of refractory dyspnea in
      COPD, outlining currently available evidence and highlighting areas for further
      investigation. Topics include oxygen, opioids, psychotropic drugs, inhaled
      furosemide, Heliox, rehabilitation, nutrition, psychosocial support, breathing
      techniques, and breathlessness clinics.

PMID- 18046868
TI  - Depression in COPD--management and quality of life considerations.
AB  - Depression is common in COPD patients. Around 40% are affected by severe
      depressive symptoms or clinical depression. It is not easy to diagnose depression
      in COPD patients because of overlapping symptoms between COPD and depression.
      However, the six-item Hamilton Depression Subscale appears to be a useful
      screening tool. Quality of life is strongly impaired in COPD patients and
      patients' quality of life emerges to be more correlated with the presence of
      depressive symptoms than with the severity of COPD. Nortriptyline and imipramine
      are effective in the treatment of depression, but little is known about the
      usefulness of newer antidepressants. In patients with milder depression,
      pulmonary rehabilitation as well as cognitive-behavioral therapy are effective.
      Little is known about the long-term outcome in COPD patients with co-morbid
      depression. Preliminary data suggest that co-morbid depression may be an
      independent protector for mortality.

PMID- 18046869
TI  - Biological targets for therapeutic interventions in COPD: clinical potential.
AB  - COPD is a widespread inflammatory respiratory disorder characterized by a
      progressive, poorly reversible airflow limitation. Currently available therapies
      are mostly based on those used to treat asthma. However, such compounds are not
      able to effectively reduce the gradual functional deterioration, as well as the
      ongoing airway and lung inflammation occurring in COPD patients. Therefore, there
      is an urgent need to improve the efficacy of the existing drug classes and to
      develop new treatments, targeting the main cellular and molecular mechanisms
      underlying disease pathogenesis. These therapeutic strategies will be highlighted
      in the present review.

PMID- 18046871
TI  - On the evolution of anti-aging medicine.

PMID- 18046870
TI  - Strategies for improving outcomes of COPD exacerbations.
AB  - COPD is uniquely situated as a chronic disease at the beginning of the 21st
      century; it is not only an established major cause of mortality and morbidity but
      is increasing in prevalence despite current medical interventions. In addition
      COPD is not a stable disease but its natural history is punctuated by periods of
      acute deterioration or exacerbations. Exacerbations generate considerable
      additional morbidity and mortality, and directly affect patients' quality of
      life. However, despite significant advances in understanding and treating this
      disease, exacerbations continue to be the major cause of COPD-associated
      hospitalization, and provision for their management incurs considerable health
      care costs. This review will consider the current management of COPD
      exacerbations and how new clinical strategies may improve outcome of these
      important clinical events.

PMID- 18046872
TI  - Interventions to reduce the adverse psychosocial impact of driving cessation on
      older adults.
AB  - As a result of our aging population, the coming years will see increasing numbers
      of older adults faced with the prospect of giving up driving due to poor health
      or functional limitations. Driving cessation has been associated with negative
      psychosocial outcomes for older adults including restricted mobility and
      depression. While several studies report evaluations of interventions designed to
      help older adults to drive safely for longer, there is a paucity of published
      research concerned with the design or implementation of intervention programs
      intended to reduce the negative consequences of driving cessation. This paper
      reviews cognitive and educational interventions designed to promote older driver
      safety, and discusses possible approaches to the design and implementation of
      clinical interventions for older adults who have ceased driving. A broad
      framework for adaptable interventions based on the theoretical tenets of social
      cognitive theory, with an emphasis on planning for cessation, problem-solving and
      the involvement of friends and family members is proposed.

PMID- 18046873
TI  - Anti-aging therapy through fitness enhancement.
AB  - Physical exercise is proposed as a highly effective means of treating and
      preventing the main causes of morbidity and mortality--most of which are
      associated with aging--in industrialized countries. Low physical fitness is an
      important risk factor for cardiovascular and all-causes morbidity and mortality;
      indeed, it is even a predictor of these problems. When properly measured, the
      assessment of physical fitness can be a highly valuable indicator of health and
      life expectancy and, therefore, should be performed routinely in the clinical
      setting. Individually adapted training programs could be prescribed based on
      fitness assessment results and an adequate knowledge of patient lifestyle and
      daily physical activity. Such training programs would allow people to develop
      their maximum physical potential, improve their physical and mental health, and
      attenuate the negative consequences of aging.

PMID- 18046874
TI  - Risk assessment for cancer surgery in elderly patients.
AB  - Global growth of the elderly population is requiring healthcare providers to
      cater for an expanding elderly cancer subpopulation. The aggression with which
      cancer should be treated in this subpopulation is an ethical dilemma and is an
      ongoing debate, as surgeons have feared increases in postoperative morbidity and
      mortality. As a result elderly patients often receive suboptimal cancer
      treatment. The need for standardization of cancer surgery is well recognized
      despite the difficulties in view of heterogeneity of the group. In this article,
      epidemiological changes, tumor biology specific to elderly cancer are visited,
      operative risk assessment tools are discussed, and interim results of ongoing
      multinational investigation ie, PACE (Preoperative Assessment of Cancer Elderly)
      revealed.

PMID- 18046875
TI  - Vascular dementia: prevention and treatment.
AB  - BACKGROUND: Vascular dementia (VaD) is the most common cause of dementia in the
      elderly, second only to Alzheimer's disease (AD). Between 1% and 4% of people of
      65 years of age suffer from VaD and the prevalence appears to double every 5-10
      years after the age of 65. SUMMARY: Prevention aims to reduce the disease by
      eliminating its cause or main risk factors, particularly hypertension as well as
      diabetes mellitus, atherosclerosis, coronary artery disease, smoking, lipid
      abnormalities, and hyperhomocystinemia. Initial studies of several agents for
      symptomatic treatment were disappointing. However, there is growing evidence for
      cholinergic involvement in VaD and recent studies with cholinesterase inhibitors
      have shown improvement in cognitive, global function, and activities of daily
      living as compared with placebo and have been well tolerated. CONCLUSION: VaD is
      a common condition and its prevalence is likely to increase. As physicians we
      need to be diligent with regards to recognition of risk factors and vigorous
      intervention. Promising results have been seen in several clinical trials of
      cholinesterase inhibitors and no safety of tolerability issues have been noted.

PMID- 18046876
TI  - Anecortave acetate in the treatment of age-related macular degeneration.
AB  - RETAANE 15mg (anecortave acetate suspension) is under investigation to treat
      exudative age-related macular degeneration (AMD), the single largest cause of
      blindness in the Western world, affecting over 15 million people in the USA.
      RETAANE suspension is a unique synthetic cortisene and has antiangiogenic
      properties that were established in multiple experimental models of angiogenesis.
      The molecule acts at multiple sites of the angiogenic cascade. Clinical trials in
      patients with exudative AMD have demonstrated the excellent safety record of both
      the drug anecortave acetate and the posterior juxtascleral depot (PJD)
      administration procedure. A pivotal study comparing RETAANE suspension with
      placebo showed a significantly higher chance of maintaining vision in the
      treatment (73%) as compared with placebo (47%). Another study compared RETAANE
      suspension with Visudyne photodynamic therapy, revealing no statistically
      significant differences between the two treatments over 24 months. AMD is a multi
      faceted disease and therefore a molecule such as RETAANE suspension with a unique
      mechanism of action, demonstrated clinical efficacy, and retreatment every six
      months is an important potential treatment option which should be further
      investigated both as a monotherapy or in combination with other treatment
      strategies.

PMID- 18046877
TI  - Citicoline (Cognizin) in the treatment of cognitive impairment.
AB  - Pharmacological treatment of cerebrovascular disorders was introduced at the
      beginning of the 20th Century. Since then, a multitude of studies have focused on
      the development of a consensus for a well defined taxonomy of these disorders and
      on the identification of specific patterns of cognitive deficits associated with
      them, but with no clear consensus. Nevertheless, citicoline has proved to be a
      valid treatment in patients with a cerebrovascular pathogenesis for memory
      disorders. A metanalysis performed on the entire database available from the
      clinical studies performed with this compound confirms the experimental evidence
      from the animal studies which have repeatedly described the multiple biological
      actions of citicoline in restoring both the cell lipid structures and some
      neurotransmitter functions.

PMID- 18046878
TI  - Effect of aging on respiratory system physiology and immunology.
AB  - With the looming expansion of the elderly population of the US, a thorough
      understanding of "normal" aging-related changes on the respiratory system is
      paramount. The respiratory system undergoes various anatomical, physiological and
      immunological changes with age. The structural changes include chest wall and
      thoracic spine deformities which impairs the total respiratory system compliance
      leading to increase work of breathing. The lung parenchyma loses its supporting
      structure causing dilation of air spaces: "senile emphysema". Respiratory muscle
      strength decreases with age and can impair effective cough, which is important
      for airway clearance. The lung matures by age 20-25 years, and thereafter aging
      is associated with progressive decline in lung function. The alveolar dead space
      increases with age, affecting arterial oxygen without impairing the carbon
      dioxide elimination. The airways receptors undergo functional changes with age
      and are less likely to respond to drugs used in younger counterparts to treat the
      same disorders. Older adults have decreased sensation of dyspnea and diminished
      ventilatory response to hypoxia and hypercapnia, making them more vulnerable to
      ventilatory failure during high demand states (ie, heart failure, pneumonia, etc)
      and possible poor outcomes.

PMID- 18046879
TI  - Orthomolecular medicine: the therapeutic use of dietary supplements for anti
      aging.
AB  - Dietary supplements at high doses as part of medical therapy have been
      controversial, but the evidence suggests that they play a significant role in
      prevention and treatment of diseases as well as protection from accelerated aging
      that results from oxygen free-radical damage, inflammation, and glycation. This
      literature review examines several supplements that have documented roles in
      medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid,
      chromium, L-carnitine, and quercetin. The evidence shows benefits in diabetes,
      cardiovascular disease, hypertension, congestive heart failure, age-related
      deterioration of brain function and vision, and immune function, as well as other
      age-related health problems.

PMID- 18046880
TI  - A five state dissemination of a community-based disability prevention program for
      older adults.
AB  - OBJECTIVE: To describe challenges in disseminating the Health Enhancement Program
      (HEP), a community-based disability prevention program for community dwelling
      elders, and to examine program effectiveness in geographically dispersed sites.
      METHODS: Within-group, pre-test-post-test comparisons of disability risk factors,
      health and functional status, and hospitalizations for 115 participants
      completing one year in HEP, and primary care provider awareness and perceptions
      of the program. RESULTS: Most (77%) participants were women, with an average age
      of 73 years and an average of 3.5 chronic conditions. At one-year follow-up,
      compared with enrollment, fewer participants were depressed (8.8% vs 15.9%),
      physically inactive (15.8% vs 38.6%), at high nutritional risk (24.3% vs 44.1%),
      or experiencing restricted activity days (35% vs 48%). Severity scores on most
      measures also improved significantly. The proportion hospitalized was unchanged
      from the year prior to HEP, although risk factors predicted an increase in
      hospitalizations as for the control group in the randomized trial. CONCLUSIONS:
      HEP reduced participants' disability risk factors. Sites varied on numbers
      enrolled and time to implement the program, likely due to differing referral
      bases, degree of physician awareness of HEP, and site readiness. However, the
      benefits of HEP participation were comparable with those reported previously.

PMID- 18046881
TI  - Body mass index and change in blood pressure over a 7-year period in older
      Mexican Americans.
AB  - Obesity and hypertension are major public health concerns in the US. We examined
      the relationship between body mass index (BMI) and blood pressure in older
      Mexican Americans using data from the Hispanic Established Population for the
      Epidemiological Study of the Elderly (EPESE), a longitudinal study of Mexican
      Americans aged 65 and over residing in the southwestern US. The study sample was
      2404 older Mexican American adults with a mean age of 72.6 years of age at
      baseline (1993-4). Both systolic and diastolic blood pressures were higher in
      subjects with high BMI categories. The rate of change in systolic blood pressure
      and diastolic blood pressure were -0.11 mm Hg and -0.32 mm Hg per year over a 7
      year period, respectively. The rate of decline in systolic and diastolic blood
      pressure over a 7-year period was greater in subjects with BMI categories of 25-
      < 30 kg/m2 and 30- < 35 kg/m2 as compared with those subjects with in the lowest
      and in the highest BMI categories. Hypertension is one of the most prevalent
      medical conditions affecting older adults. Understanding possible modifiable risk
      factors that may play a role in the management of hypertension will be
      beneficial.

PMID- 18046882
TI  - BMI and low bone mass in an elderly male nursing home population.
AB  - INTRODUCTION: Little is known about osteoporosis in institutionalized older
      adults. Risk factors such as low body mass index (BMI) have been investigated in
      female populations, but remain understudied in men. The objective of this study
      was to examine characteristics of older men residing in a nursing home who
      received bone mineral density evaluations. METHODS: 57 male Miami Veterans
      Affairs Medical Center (VAMC) nursing home residents were screened for
      osteoporosis using a peripheral dual X-ray (pDXA) technique. T-scores were
      categorized into three groups: normal (0 > -1); osteopenic (-1 to -2.49);
      osteoporotic (< -2.5). RESULTS: Average age was 76.2 years (standard deviation =
      11.5; range: 48-100). T-scores indicated that 37.3% of the population was normal,
      35.6% osteopenic, and 27.1% osteoporotic. 35.6% of patients had normal BMIs, 3.4%
      were underweight, 47.5% were overweight, and 13.6% were considered obese. There
      was a high prevalence of overweight and obese individuals (61.1%) in the
      osteopenic and osteoporotic groups. CONCLUSION: As expected, there was a high
      prevalence of low bone mass in our population (62%). However, overweight and
      obese men were more likely to have osteoporosis and osteopenia, contrary to
      literature and clinical knowledge. This finding may be partially explained by the
      prevalence of sedentary lifestyle and relative lack of weight-bearing activity in
      this group of men.

PMID- 18046883
TI  - Are hypertensive elderly patients treated differently?
AB  - OBJECTIVES: 1. To determine if there are differences in the classes of
      antihypertensive agents prescribed for the elderly population as compared with
      younger patients. 2. To compare patterns of antihypertensive therapy with
      established national guidelines. DESIGN: National Ambulatory Medical Care Survey
      (NAMCS) database analysis from 1995-2000. SETTING: Multiple outpatient clinic
      settings in the US. PARTICIPANTS: Primary care and sub-specialty physicians and
      their patients. MEASUREMENTS: 332510280 outpatient visits with an ICD-9 code
      corresponding to a diagnosis of hypertension were analyzed. The class(es) of
      antihypertensive medications that patients were already taking and/or those added
      in that visit were noted. Demographics of the patients were also analyzed.
      RESULTS: There was a statistically significant association between the
      prescription of diuretics, calcium-channel blockers (CCBs), alpha-1-blockers
      (A1Bs), alpha-2 agonists (A2Ags) and age > or = 65 years. CONCLUSION: Patients
      aged 65 and over were prescribed different types of medications than those under
      age 65. Increased usage of diuretics and CCBs were in accordance with evidence
      based guidelines for this group. A1Bs were likely used more due to co-morbid
      benign prostatic hyperplasia (BPH), but this is not certain. The increased
      prescription of A2Ags likely reflects long-term usage of these medications, which
      nonetheless may be hazardous due to their potential for causing increased
      cognitive dysfunction in the aged.

PMID- 18046884
TI  - Effectiveness of two Arthritis Foundation programs: Walk With Ease, and YOU Can
      Break the Pain Cycle.
AB  - OBJECTIVE: To evaluate the effectiveness of two Arthritis Foundation programs:
      Walk With Ease (WWE) and YOU Can Break The Pain Cycle (PC). DESIGN: Quasi
      experimental, repeated measures design. Retested at six weeks and four months.
      SETTING: Community based intervention. PARTICIPANTS: Volunteer sample of 163
      adults with arthritis recruited through mailings, newspapers, and flyers.
      INTERVENTIONS: Subjects participated in a 90 minute seminar (PC, Group A), a six
      week walking program (WWE, Group B), or both programs (Group C). MAIN OUTCOME
      MEASURES: Survey assessment of arthritis knowledge, general health, self
      management activities, confidence, physical abilities, depression, health
      distress, and how arthritis affects their life. A Squat Test, a Six Minute Walk
      test, and a Timed Functional Walk Test were also administered. RESULTS: Subjects
      in Group B were more confident, less depressed, had less health distress, and
      less pain than subjects in Group A. Scores of Group C were between Group A and B
      scores. Differences in groups over time indicated that the WWE resulted in
      increased confidence, physical abilities, time spent in self-management
      activities and decreased pain and fatigue. All groups increased in walking
      endurance at six weeks, and increased in health distress at four months.
      CONCLUSION: Subjects in different programs differed on impact of arthritis. These
      programs provide effective arthritis management opportunities.

PMID- 18046885
TI  - The big picture and the little picture.

PMID- 18046886
TI  - The role for N-acetylcysteine in the management of COPD.
AB  - Oxidative stress has been implicated in the pathogenesis and progression of COPD.
      Both reactive oxidant species from inhaled cigarette smoke and those endogenously
      formed by inflammatory cells constitute an increased intrapulmonary oxidant
      burden. Structural changes to essential components of the lung are caused by
      oxidative stress, contributing to irreversible damage of both parenchyma and
      airway walls. The antioxidant N-acetylcysteine (NAC), a glutathione precursor,
      has been applied in these patients to reduce symptoms, exacerbations, and the
      accelerated lung function decline. This article reviews the available
      experimental and clinical data on the antioxidative effects of NAC in COPD, with
      emphasis on the role of exhaled biomarkers.

PMID- 18046887
TI  - Tiotropium bromide.
AB  - Therapy with bronchodilators forms the pharmacologic foundation of the treatment
      of patients with COPD. Bronchodilators can significantly lessen dyspnea, increase
      airflow, improve quality of life, and enhance exercise performance. While
      bronchodilators decrease airway resistance and lessen dynamic hyperinflation in
      patients with COPD, they have not been shown to alter the rate of decline in FEV1
      over time, or improve patient survival. Fairly recently, a long-acting, once
      daily anticholinergic medication, tiotropium bromide, has been developed which
      may improve symptom management in COPD patients. This paper reviews
      anticholinergic pharmacologic therapy for patients with COPD focusing on
      tiotropium bromide, and discusses treatment strategies based on disease stage. It
      is important to recognize that while bronchodilators improve symptoms, a
      multimodality treatment approach including respiratory and rehabilitative
      therapy, nutrition services, psychosocial counseling, and surgical care, is often
      necessary for the best possible care of patients with COPD.

PMID- 18046888
TI  - Budesonide-formoterol (inhalation powder) in the treatment of COPD.
AB  - The budesonide-formoterol dry powder inhaler (Symbicort Turbuhaler 160/ 4.5
      640/18 microg/day) contains the long-acting beta2-adrenoreceptor agonist
      formoterol and the inhaled corticosteroid budesonide. Two large, 12-month trials
      examined the effect of budesonide-formoterol 160/4.5 microg twice daily in COPD
      patients who met these criteria. The studies were identical, except one in which
      the patients had received oral prednisolone 30 mg/ day and had inhaled formoterol
      4.5 microg twice daily for 2 weeks before randomization. In terms of the FEV1,
      budesonide-formoterol produced an effect greater than that of both budesonide
      alone and formoterol alone reported in previous studies. The combination was
      generally more effective than either of the components in terms of peak
      expiratory flow, symptoms, and exacerbations. These advantages of the combination
      over those of either budesonide alone or formoterol alone were quite consistent.
      Improving lung function and decreasing symptoms significantly, budesonide
      formoterol combination therapy provides significant clinical improvements in
      COPD, despite the limited reversibility of impaired lung function in the disease.

PMID- 18046889
TI  - Role of mucolytics in the management of COPD.
AB  - There is, to date, no medical therapy that modifies the decline in lung function
      that occurs in COPD. As the disease becomes more severe, exacerbations of COPD
      become increasingly common, affecting patient quality of life and increasing
      health care costs. Mucolytic agents, through their actions on inflammatory and
      oxidative pathways, have potential benefits in COPD. This paper reviews the
      randomized controlled trial (RCT) evidence for the effectiveness of at least 2
      months of daily therapy with oral mucolytics in COPD. Based on evidence from 26
      RCTs, mucolytics reduce exacerbations by up to 0.8 exacerbations per year, with a
      greater effect in patients with more severe COPD. This effect appears to be of a
      similar magnitude to the reduction in exacerbations seen with tiotropium and
      inhaled corticosteroids (ICS), but RCTs that compared the agents would be
      required to confirm this. Mucolytics do not affect the rate of lung function
      decline, but they do not have any significant adverse effects. Mucolytic
      treatment should be considered in: patients with more severe COPD who have
      frequent or prolonged exacerbations; those who are repeatedly admitted to
      hospital; or in those patients with frequent exacerbations who are unable to take
      tiotropium or ICS.

PMID- 18046890
TI  - Current status of noninvasive ventilation in stable COPD patients.
AB  - Noninvasive ventilation (NIV) has been one of the major advances in respiratory
      medicine in the last decade. NIV improves quality of life, prolongs survival, and
      improves gas exchange and sleep quality in restrictive patients, but evidence
      available now does not allow us to establish clear criteria for prescribing NIV
      in patients with chronic respiratory failure due to COPD. On the basis of the
      available studies, NIV should not be used as a treatment of choice for all
      patients with COPD, even when disease is severe. However, there is more evidence
      that NIV has an important effect in these patients. In fact, a selected group of
      patients may well benefit from domiciliary mechanical ventilation, and we need to
      be able to identify who they are. Moreover, NIV can be a new strategy to improve
      exercise tolerance in COPD patients.

PMID- 18046892
TI  - Alpha1-antitrypsin deficiency: current perspective on research, diagnosis, and
      management.
AB  - The Alpha One International Registry (AIR), a multinational research program
      focused on alpha1-antitrypsin (AAT) deficiency, was formed in response to a World
      Health Organization recommendation. Each of the nearly 20 participating countries
      maintains a national registry of patients with AAT deficiency and contributes to
      an international database located in Malmo, Sweden. This database is designed to
      increase understanding of AAT deficiency. Additionally, AIR members are engaged
      in active, wide-ranging investigations to improve the diagnosis, monitoring, and
      treatment of the disease and meet biennially to exchange views and research
      findings. The fourth biennial meeting was held in Copenhagen, Denmark, on 2-3
      June 2005. This review covers the wide range of AAT deficiency-related topics
      that were addressed encompassing advances in genetic characterization, risk
      factor identification, clinical epidemiology, inflammatory and signalling
      processes, therapeutic advances, and lung imaging techniques.

PMID- 18046891
TI  - Emerging role of MAP kinase pathways as therapeutic targets in COPD.
AB  - Studies examining the cellular mechanisms of inflammation and protease production
      in the lung tissue and airways of COPD patients have shed light on the important
      role of kinase-based signaling cascades. These pathways can be activated by
      environmental stimuli such as tobacco smoke, and by endogenous signals such as
      cytokines, growth factors, and inflammation-derived oxidants. The three most
      widely characterized cascades are those directed by the classical mitogen
      activated protein (MAP) kinase (ERK1/2), stress activated protein kinase/c-Jun N
      terminal protein kinase, and p38 enzymes. These phosphorylation cascades transmit
      and amplify extracellular, receptor-mediated signals through the cytoplasm of the
      cell to activate nuclear transcription factors which bind and induce expression
      of target genes. The result is tight control of diverse cellular events, and
      rapid responses to external stimuli. However, recent research suggests that
      constitutive or aberrant activation of MAP kinases contributes to several COPD
      associated phenotypes, including mucus overproduction and secretion,
      inflammation, cytokine expression, apoptosis, T cell activation, matrix
      metalloproteinase production, and fibrosis. This review explores the biological
      functions of the MAP kinase pathways in the pathogenesis of COPD, their
      activation by cigarette smoke, and discusses the potential role of MAP kinase
      inhibitors in COPD therapy.

PMID- 18046893
TI  - Apoptotic mechanisms in the pathogenesis of COPD.
AB  - COPD is a leading cause of morbidity and mortality, characterized by a chronic
      abnormal inflammatory response to noxious agents. Apoptosis is a physiologic
      process, critical to cellular homeostasis, in which cell death follows a
      programmed sequence of events. Apoptosis has been recognized to play an important
      role in clinical and experimental models of lung diseases. Abnormal apoptotic
      events in smokers' and in emphysematous lungs have been shown in epithelial and
      endotheliallung cells, neutrophils, lymphocytes, and myocytes. Many factors
      associated with COPD, including cigarette smoke, have the potential to cause
      apoptosis of alveolar epithelial cells, the main sites of vascular endothelial
      growth factor (VEGF) production. The decreased expression of VEGF, a known
      survival factor for endothelial cells, and its receptor, results in lung septal
      endothelial cell death, leading perhaps to the emphysema observed in COPD. In
      smokers who develop COPD there is an activation of adaptive immunity, with an
      infiltration of CD4+ and, especially, CD8 + cells. CD8 + cells are cytotoxic to
      epithelial cells through the release of granzymes and perforin, which can further
      induce apoptosis of alveolar cells. Moreover, any reduction in neutrophil
      apoptosis or dysregulation of macrophage uptake of apoptotic neutrophils could
      lead to chronic inflammation and tissue injury. Increased rates of T-cell
      apoptosis may lead to a defective immune response to infective organisms,
      contributing to the high frequency of infections seen in COPD. Increased
      apoptosis of skeletal muscle could be responsible for the skeletal muscle
      atrophy, the main cause of unexplained weight loss in patients with COPD. This
      paper is a review of the current knowledge on the apoptotic pathways involved in
      COPD pathogenesis and their interaction with other known contributing factors.

PMID- 18046894
TI  - Oxidative and nitrosative stress in the diaphragm of patients with COPD.
AB  - COPD is associated with an increased load on the diaphragm. Since chronic muscle
      loading results in changes in antioxidant capacity and formation of reactive
      oxygen and reactive nitrogen species, we hypothesized that COPD has a similar
      effect on the diaphragm, which is related to the severity of COPD. Catalase
      activity was determined spectrophotometrically. Levels of 4-hydroxy-2-nonenal
      (HNE)-protein adducts and 3-nitrotyrosine (NT) formation were measured using
      western blotting. Levels of malondialdehyde (MDA) were assessed by high
      performance liquid chromatography. We found that catalase activity was
      approximately 89% higher in the diaphragm of severe COPD patients (FEV1 37+/-5%
      predicted) compared with non-COPD patients. MDA levels, a marker for lipid
      peroxidation, were significantly lower in the diaphragm of COPD patients compared
      with non-COPD patients, whereas the level of HNE-protein adducts was equal in
      both groups. NT formation was not different between groups. However, increasing
      hyperinflation and NT formation were inversely correlated. These results indicate
      that in COPD the diaphragm adapts to a higher work load by increasing catalase
      activity, resulting in a reduction in oxidative damage to lipids and tyrosine
      nitration of proteins.

PMID- 18046895
TI  - Physiological associations of computerized tomography lung density: a factor
      analysis.
AB  - BACKGROUND: Objective quantification of emphysema using computerized tomography
      (CT) density measurements is rapidly gaining wide acceptance as an in vivo
      measurement tool. However, some studies have suggested that abnormal lung
      function in the absence of emphysema can affect lung density, and the role of
      such measurements in identifying and monitoring the progression of emphysema is
      not clear. OBJECTIVE: To clarify the relationship between lung density
      measurements and pulmonary function. METHODS: CT measurements of the proportion
      of lung occupied by low density tissue (as percentage of lung area below
      predetermined Hounsfield unit [HU] thresholds) were obtained in a large random
      population (n = 739) and the association with detailed pulmonary function tests
      studied using factor analysis. RESULTS: Density measurements showed a greater
      association with measures of hyperinflation and airflow obstruction than measures
      of gas transfer (correlation coefficient, high resolution scan, -950HU threshold
      vs FEV1/FVC, RV, and DLCO/VA of -0.39, 0.22, and -0.15 respectively). The
      strongest lung density factor coefficients of 0.51 (standard resolution scan, -
      950 HU threshold) and 0.46 (high resolution scan, - 910 HU threshold) were seen
      with factors predominantly consisting of measures of airflow obstruction and
      hyperinflation. Most variation in lung density was not accounted for by lung
      function measurements (communality 0.21-0.34). CONCLUSION: Lung density
      measurements associate most strongly with measures of airway disease that are not
      specific to emphysema.

PMID- 18046896
TI  - Local lung responses following endobronchial elastase and lipopolysaccharide
      instillation in sheep.
AB  - Chronic lipopolysaccharide (LPS) exposure may contribute to the pathogenesis of a
      number of lung diseases including COPD and emphysema. We sought to develop a
      large-animal model of emphysema using repeated LPS administration into sheep lung
      segments. An experimental protocol was designed to facilitate comparisons with
      elastase-treated and control segments within the same lung of individual sheep.
      Histopathologic evaluation of segments treated with LPS demonstrated low-grade
      inflammation characterized by an increase in the number of intra-alveolar
      macrophages and lymphocytes. Treated segments demonstrated a significant
      reduction in airspace surface area (ASA), an increase in percent disrupted
      alveolar attachments and the distance between normal alveolar attachments, and a
      reduction in the number of normal alveolar attachments surrounding nonrespiratory
      bronchioles. Coefficient of variation of individual ASA measurements in elastase
      treated segments was indicative of a heterogeneous parenchymal response, in
      contrast to that associated with chronic LPS treatment. Our results demonstrate
      that chronic LPS treatment of individual lung segments in sheep induces
      microscopic emphysema qualitatively and quantitatively consistent with both
      accepted pathologic definitions of this condition and with that produced by
      airway instillation of elastolytic enzymes. Development of this phenotype is
      associated with evidence of downregulated activation of transforming growth
      factor beta.

PMID- 18046897
TI  - Functional results of unilateral lung volume reduction surgery in alpha1
      antitrypsin deficient patients.
AB  - Lung volume reduction surgery (LVRS) has been shown to improve lung function and
      exercise tolerance in patients with severe emphysema. Some predictors of poor
      outcome have been described but the role of alpha1-antitrypsin (alpha1-AT)
      deficiency is still not well known. The aim of this study was to analyze the
      results of unilateral LVRS in our center according to the alpha1-AT status. The
      results of LVRS in 17 deficient patients and 35 nondeficient patients were
      analyzed at 3-6 months and 1 year after surgery. Compared with baseline, a
      significant improvement of FEV1, partial pressure in arterial blood (PaO2),
      dyspnea score and walking distance was observed in the two groups at 3-6 months
      after surgery and the studied parameters remained significantly improved at 1
      year in the nondeficient group. By contrast, PaO2 and walking distance returned
      towards baseline in the deficient group at 1 year whereas improvement of FEV1 and
      dyspnea score was persistent. Mean values of FEV, at baseline, 3-6 months, and 1
      year were 22 +/- 6%, 29 +/- 11%, and 26 +/- 9% and 28 +/- 12%, 38 +/- 17%, and 40
      +/- 17% predicted in the deficient group and in the non-deficient group,
      respectively. In conclusion, the functional benefit is short-lasting in alpha1-AT
      deficient patients after unilateral LVRS.

PMID- 18046898
TI  - The history of COPD.
AB  - The evolution of knowledge concerning COPD and its components--emphysema, chronic
      bronchitis, and asthmatic bronchitis--covers 200 years. The stethoscope and
      spirometer became important early tools in diagnosis and assessment. Spirometry
      remains the most effective means of identification and assessment of the course
      of COPD and responses to therapy, and is grossly underused for this purpose.
      Knowledge of the pathogenesis, course and prognosis, and new approaches to
      therapy have dramatically improved our understanding of this important clinical
      entity. Smoking cessation improves the early course of disease. Long-term oxygen
      improves the length and quality of life in selected patients with hypoxemia.
      Surgery benefits a select few. Today, COPD is a steadily growing global
      healthcare problem, with increasing morbidity and mortality. Early identification
      and prevention, and treatment of emerging stages of disease through smoking
      cessation and a growing number of bronchoactive drugs promises to change the
      outcome.

PMID- 18046899
TI  - Antioxidant therapies in COPD.
AB  - Oxidative stress is an important feature in the pathogenesis of COPD. Targeting
      oxidative stress with antioxidants or boosting the endogenous levels of
      antioxidants is likely to be beneficial in the treatment of COPD. Antioxidant
      agents such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl
      L-cysteine and N-acystelyn), dietary polyphenols (curcumin, resveratrol, green
      tea, catechins/quercetin), erdosteine, and carbocysteine lysine salt, all have
      been reported to control nuclear factor-kappaB (NF-kappaB) activation, regulation
      of glutathione biosynthesis genes, chromatin remodeling, and hence inflammatory
      gene expression. Specific spin traps such as alpha-phenyl-N-tert-butyl nitrone, a
      catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113),
      and a superoxide dismutase mimetic M40419 have also been reported to inhibit
      cigarette smoke-induced inflammatory responses in vivo. Since a variety of
      oxidants, free radicals, and aldehydes are implicated in the pathogenesis of
      COPD, it is possible that therapeutic administration of multiple antioxidants
      will be effective in the treatment of COPD. Various approaches to enhance lung
      antioxidant capacity and clinical trials of antioxidant compounds in COPD are
      discussed.

PMID- 18046900
TI  - Akt in the pathogenesis of COPD.
AB  - In this review we consider the therapeutic potential of targeting Akt for the
      treatment of COPD. Akt is a serine/threonine protein kinase that functions as a
      signaling intermediate linked to multiple signaling programs involved in
      survival, inflammation, and growth. Akt is closely associated with key membrane
      bound receptors and represents a convergent integration point for multiple
      stimuli implicated in COPD pathogenesis. Persistent activation of Akt secondary
      to somatic mutations in regulatory oncogenes, such as PTEN, may explain why
      inflammation in COPD does not resolve when smoking is ceased. Akt is also
      implicated in the systemic manifestations of COPD such as skeletal muscle wasting
      and metabolic disturbances. Furthermore, targeting Akt may provide a useful means
      of limiting the severity and duration of disease exacerbations in COPD. As such,
      Akt represents a particularly attractive therapeutic target for the treatment of
      COPD. Interestingly, current knowledge suggests that both inhibitors and
      activators of Akt may be useful for treating different clinical subpopulations of
      COPD patients.

PMID- 18046901
TI  - Eosinophilic airway inflammation in COPD.
AB  - Chronic obstructive pulmonary disease is a common condition and a major cause of
      mortality. COPD is characterized by irreversible airflow obstruction. The
      physiological abnormalities observed in COPD are due to a combination of
      emphysema and obliteration of the small airways in association with airway
      inflammation. The predominant cells involved in this inflammatory response are
      CD8+ lymphocytes, neutrophils, and macrophages. Although eosinophilic airway
      inflammation is usually considered a feature of asthma, it has been demonstrated
      in large and small airway tissue samples and in 20%-40% of induced sputum samples
      from patients with stable COPD. This airway eosinophilia is increased in
      exacerbations. Thus, modifying eosinophilic inflammation may be a potential
      therapeutic target in COPD. Eosinophilic airway inflammation is resistant to
      inhaled corticosteroid therapy, but does respond to systemic corticosteroid
      therapy, and the degree of response is related to the intensity of the
      eosinophilic inflammation. In COPD, targeting treatment to normalize the sputum
      eosinophilia reduced the number of hospital admissions. Whether controlling
      eosinophilic inflammation in COPD patients with an airway eosinophilia will
      modify disease progression and possibly alter mortality is unknown, but warrants
      further investigation.

PMID- 18046903
TI  - Depression in the patient with COPD.
AB  - This paper explores the recent literature surrounding comorbid depression and
      COPD. The literature reveals a high prevalence of depression in patients with
      COPD and some evidence that the depression is a result of the disease. The
      literature highlights the negative impact of depression on quality of life and a
      possible impact on mortality. Depression also negatively impacts on compliance
      and smoking cessation. Treatment of depression in COPD, particularly by cognitive
      behavioral therapy, has positive impact on quality of life. Tricyclic
      antidepressants have a positive impact on mood and COPD, but side effects limit
      their use. The advent of the new antidepressants may improve acceptability and
      outcomes, but the research is yet to be undertaken. Physical rehabilitation may
      have a positive impact on mood. This paper highlights the difficulty in screening
      for depression in patients with COPD due to the overlap of symptoms between the
      two diseases. Despite the difficulties, it is important to recognize and treat
      depression in patients with COPD because of the significant likelihood of
      improvement in quality of life.

PMID- 18046902
TI  - Clinical implications of airway hyperresponsiveness in COPD.
AB  - COPD represents one of the leading causes of mortality in the general population.
      This study aimed at evaluating the relationship between airway
      hyperresponsiveness (AHR) and COPD and its relevance for clinical practice. We
      performed a MEDLINE search that yielded a total of 1919 articles. Eligible
      studies were defined as articles that addressed specific aspects of AHR in COPD,
      such as prevalence, pathogenesis, or prognosis. AHR appears to be present in at
      least one out of two individuals with COPD. The occurrence of AHR in COPD is
      influenced by multiple mechanisms, among which impairment of factors that oppose
      airway narrowing plays an important role. The main determinants of AHR are
      reduction in lung function and smoking status. We envision a dual role of AHR: in
      suspected COPD, specific determinants of AHR, such as reactivity and the plateau
      response, may help the physician to discriminate COPD from asthma; in definite
      COPD, AHR may be relevant for the prognosis. Indeed, AHR is an independent
      predictor of mortality in COPD patients. Smoking cessation has been shown to
      reduce AHR. Further studies are needed to elucidate whether this functional
      change is associated with improvement in lung function and respiratory symptoms.

PMID- 18046904
TI  - Is there a role for mask continuous positive airway pressure in acute respiratory
      failure due to COPD? Lessons from a retrospective audit of 3 different cohorts.
AB  - Exacerbations of COPD that result in acute respiratory failure requiring
      intubation and mechanical ventilation have high morbidity and mortality. This
      study is a retrospective observational study that compared the outcomes of 237
      patients with COPD and acute respiratory failure requiring intensive care unit
      (ICU) admission according to modality of initial therapy: mask continuous
      positive airway pressure (CPAP), medical therapy, or intubation. Of the patients
      treated with CPAP initially, only 16% failed and required intubation compared
      with 62% of those treated medically (p = 0.001). The median length of ICU stay
      was 5 days in those treated with CPAP, compared with 7 days for those medically
      treated, and 8.5 days for intubated patients (p = 0.001). When compared with mask
      CPAP, and after adjusting for potentially confounding differences, mortality was
      significantly higher if patients were initially intubated (adjusted odds ratios
      [OR] 15.7; 95% confidence interval [CI] 4.2, 59) or given medical therapy (OR
      5.1; CI 1.2, 20.8). In COPD patients with acute respiratory failure, initial
      treatment with mask CPAP was associated with significantly better outcomes than
      other treatment modalities, even after adjusting for potentially confounding
      differences in disease severity.

PMID- 18046905
TI  - Lower limb vasodilatory capacity is not reduced in patients with moderate COPD.
AB  - We compared exercise capacity (peak O2 uptake; VO(2peak)) and lower limb
      vasodilatory capacity in 9 patients with moderate COPD (FEV1 52.7 +/- 7.6%
      predicted) and 9 age-matched healthy control subjects. VO(2peak) was measured via
      open circuit spirometry during incremental cycling. Calf blood flow (CBF)
      measurements were obtained at rest and after 5 minutes of ischemia using venous
      occlusion plethysmography. While VO(2peak) was significantly lower in the COPD
      patients (15.8 +/- 3.5 mL x kg(-1) x min(-1)) compared with the control group
      (25.2 +/- 3.5 mL x kg(-1) x min(-1)), there were no significant differences
      between groups in peak CBF or peak calf conductance measured 7 seconds post
      ischemia. VO(2peak) was significantly correlated with peak CBF and peak
      conductance in the control group, whereas no significant relationship was found
      between these variables in the COPD group. However, the rate of decay in blood
      flow following ischemia was significantly slower (p < 0.05) for the COPD group (
      0.036 +/- 0.005 mL x 100 mL(-1) x min(-1) x S(-1)) when compared with controls (
      0.048 +/- 0.015 mL x 100 mL(-1) x min(-1) x S(-1)). The results suggest that the
      lower peak exercise capacity in patients with moderate COPD is not related to a
      loss in leg vasodilatory capacity.

PMID- 18046906
TI  - Mitochondrial function in diaphragm of emphysematous hamsters after treatment
      with nandrolone.
AB  - Respiratory failure in patients with COPD may be caused by insufficient force
      production or insufficient endurance capacity of the respiratory muscles.
      Anabolic steroids may improve respiratory muscle function in COPD. The effect of
      anabolic steroids on mitochondrial function in the diaphragm in emphysema is
      unknown. In an emphysematous male hamster model, we investigated whether
      administration of the anabolic steroid nandrolone decanoate (ND) altered the
      activity of mitochondrial respiratory chain complexes in the diaphragm. The
      bodyweight of hamsters treated with ND was decreased after treatment compared
      with initial values, and serum testosterone levels were significantly lower in
      hamsters treated with ND than in control hamsters. No difference in the activity
      of mitochondrial respiratory chain complexes in the diaphragm between normal and
      emphysematous hamsters was observed. Treatment with ND did not change the
      activity of mitochondrial respiratory chain complexes in the diaphragm of both
      normal and emphysematous hamsters. In emphysematous hamsters, administration of
      ND decreased the activity of succinate:cytochrome c oxidoreductase compared with
      ND treatment in normal hamsters. We conclude that anabolic steroids have negative
      effects on the activity of succinate:cytochrome c oxidoreductase and anabolic
      status in this emphysematous hamster model.

PMID- 18046907
TI  - Does the multidimensional grading system (BODE) correspond to differences in
      health status of patients with COPD?
AB  - STUDY OBJECTIVES: To verify whether and to what extent the body mass index,
      airflow obstruction, dyspnea, and exercise capacity (BODE) index correlates with
      a disease-specific index of health status in patients with COPD. DESIGN: Cross
      sectional study. SETTING: University-affiliated hospital. PATIENTS: One hundred
      patients with stable COPD recruited from the outpatient clinic of a single
      institution. MEASUREMENTS: The BODE index was calculated for each patient using
      variables obtained within 2 weeks of enrollment. At enrollment, all patients
      completed the St George's Respiratory Questionnaire (SGRQ). The Kruskal-Wallis
      test was used to compare health status scores with clinical and functional
      categories of COPD. The Spearman correlation coefficient (r) was calculated to
      assess the association between health status scores and clinical or functional
      variables. RESULTS: Categorizing the BODE scores into 4 quartiles, we found that
      higher BODE quartiles were associated with higher (worse) SGRQ scores. The
      differences among the BODE quartiles in health status indexes were significant
      for total SGRQ as well as all 3 of the SGRQ subscales. In all sections of the
      SGRQ, scores were moderately to strongly associated with the BODE quartiles (r =
      0.27-0.46). In contrast, the association between the SGRQ total, impacts,
      activity and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages
      were weaker (r = 0.27-0.28). There was no significant association between SGRQ
      symptoms and GOLD stages. CONCLUSIONS: The BODE scoring system corresponds to
      important differences in health status of patients with COPD. This grading system
      is better correlated to the health status indexes of the SGRQ than the GOLD
      staging criteria.

PMID- 18046908
TI  - Sermorelin: a better approach to management of adult-onset growth hormone
      insufficiency?

PMID- 18046909
TI  - Treatment of overactive bladder in the aging population: focus on darifenacin.
AB  - Anticholinergics are commonly used in primary and secondary care settings for the
      treatment of overactive bladder syndrome. The number of anticholinergic drugs
      available on the market is increasing and various studies, both observational and
      randomized controlled trials, have evaluated effectiveness of the different
      preparations available. When anticholinergic therapy is prescribed, there is
      still uncertainty about which anticholinergic drugs are most effective, at which
      dose, and by which route of administration. There is also uncertainty about the
      role of anticholinergic drugs in different patient groups, particularly in the
      elderly. The rationale for using anticholinergic drugs in the treatment of
      overactive bladder syndrome is to block the parasympathetic acetylcholine pathway
      and thus abolish or reduce the intensity of detrusor muscle contraction. There
      are currently five recognized subtypes of muscarinic receptor; the M1, M2, and M3
      subtypes are of interest in bladder activity. Muscarinic receptors are found in
      other parts of the body, eg, in the gut, salivary glands, tear ducts. Side
      effects associated with non-selective antimuscarinics can be particularly
      distressing in the elderly. The development of bladder selective M3 specific
      antagonists has the advantage of providing increased efficacy with minimal side
      effects. Darifenacin is one such preparation. The aim of this review is to assess
      the pharmacology, interactions and the safety and tolerability of darifenacin in
      the treatment of overactive bladder in the elderly population with particular
      reference to clinical trial data available.

PMID- 18046910
TI  - Utility of tolcapone in fluctuating Parkinson's disease.
AB  - Fluctuating Parkinson's disease (PD) represents a clinical management challenge.
      The primary utility of levodopa in patients with PD is moderated by the "wearing
      off" phenomena seen with long-term use. COMT inhibitors slow down the rapid
      metabolism of levodopa, resulting in a more-sustained response to dopaminergic
      therapy. Tolcapone is a selective, reversible catechol-O-methyltransferase (COMT)
      inhibitor, shown to have both peripheral and central effects. In clinical trials,
      tolcapone has been shown to reduce "off" time, increase "on" time, improve
      patient and clinician assessments of disease severity, and improve patient
      quality of life. In a SWITCH study, tolcapone was associated with greater
      duration of "on" time than remaining on entacapone. Adverse effects of tolcapone
      are related to the class, with the exception of rare cases of hepatotoxicity.
      Tolcapone has been recently reintroduced on the European market and recent
      guidance from the US Food and Drug Administration has reduced the hepatic
      monitoring requirements for patients initiating tolcapone therapy. With proper
      monitoring, tolcapone is an effective, well-tolerated drug useful in the
      management of patients with fluctuating PD.

PMID- 18046912
TI  - Principles of soft tissue augmentation for the aging face.
AB  - In the quest for the "ideal" soft tissue filler, many diverse products have been
      developed. The expanding market of available fillers is a testament that no one
      product will ideally suit all patients or clinicians. In addition, the challenge
      of satisfying the criteria of an ideal filler has driven researchers to take a
      variety of development paths. This has resulted in multiple categories to
      characterize soft tissue fillers. These fillers are categorized according to: (1)
      filler material, eg, autologous, natural, synthetic; (2) mechanism of action, eg,
      void filler, neocollagenesis, fibroblast stimulation; (3) patient type and
      profile, eg, younger versus older patient, rhytids versus "sinking and sagging"
      skin; or (4) durability of treatment effects, eg, temporary, semi-permanent, or
      permanent. Although strategies for soft tissue augmentation may be quite diverse,
      strategies should share a universal goal to address fat redistribution (atrophy
      and hypertrophy), the primary underlying morphological cause of facial aging. To
      accomplish this, volumizers are now available that are injected more deeply,
      resulting in the restoration of supportive structure and foundation. These can be
      used in combination with other products that are used more superficially for
      smoothing skin surfaces. As numerous soft tissue fillers enter the market,
      mechanisms and injection techniques become more divergent, and therefore require
      that the dermatologist and cosmetic surgeon receive adequate training to use
      products safely and effectively. This manuscript provides an overview of soft
      tissue fillers and their proper use.

PMID- 18046911
TI  - Retinoids in the treatment of skin aging: an overview of clinical efficacy and
      safety.
AB  - Aging of skin is an intricate biological process consisting of two types. While
      intrinsic or chronological aging is an inevitable process, photoaging involves
      the premature aging of skin occurring due to cumulative exposure to ultraviolet
      radiation. Chronological and photoaging both have clinically differentiable
      manifestations. Various natural and synthetic retinoids have been explored for
      the treatment of aging and many of them have shown histological and clinical
      improvement, but most of the studies have been carried out in patients presenting
      with photoaged skin. Amongst the retinoids, tretinoin possibly is the most potent
      and certainly the most widely investigated retinoid for photoaging therapy.
      Although retinoids show promise in the treatment of skin aging, irritant
      reactions such as burning, scaling or dermatitis associated with retinoid therapy
      limit their acceptance by patients. This problem is more prominent with tretinoin
      and tazarotene whereas other retinoids mainly represented by retinaldehyde and
      retinol are considerably less irritating. In order to minimize these side
      effects, various novel drug delivery systems have been developed. In particular,
      nanoparticles have shown a good potential in improving the stability,
      tolerability and efficacy ofretinoids like tretinoin and retinol. However, more
      elaborate clinical studies are required to confirm their advantage in the
      delivery of topical retinoids.

PMID- 18046913
TI  - Candesartan in heart failure.
AB  - Candesartan cilexetil is a nonpeptide selective blocker of the angiotensin II
      receptor sub-type 1. It is a prodrug that is converted to its active metabolite
      during its variable absorption. It is highly protein bound with a small volume of
      distribution and a nine-hour half-life. Candesartan is one of two angiotensin
      receptor blockers approved for use in heart failure. MEDLINE was searched using
      OVID and PubMed to evaluate the evidence for using candesartan in patients with
      heart failure. Pharmacologic and pharmacokinetic evaluations, as well as clinical
      trials, were selected and are presented in this review. Clinical evidence
      supports the indication for use in systolic heart failure. Results for use in
      patients with diastolic heart failure were non-significant. Candesartan was well
      tolerated in the trials, with hyperkalemia, renal dysfunction, and hypotension
      being the most common adverse events. Use of angiotensin receptor blockers with
      angiotensin-converting enzyme inhibitors needs further study; however,
      candesartan appears to provide added benefit in this setting. Candesartan is a
      safe and effective option for patients with systolic heart failure. Data
      regarding other angiotensin receptor blockers is underway.

PMID- 18046914
TI  - Strontium ranelate: a novel treatment for postmenopausal osteoporosis: a review
      of safety and efficacy.
AB  - Strontium ranelate is a new orally administered agent for the treatment of women
      with postmenopausal osteoporosis that reduces the risk of vertebral and hip
      fractures. Evidence for the safety and efficacy of strontium ranelate comes from
      two large multinational trials, the SOTI (Spinal Osteoporosis Therapeutic
      Intervention) and TROPOS (Treatment Of Postmenopausal Osteoporosis) studies. The
      SOTI study evaluated vertebral fracture prevention in 1649 postmenopausal women
      with a mean age of 69 y. The subjects all had at least one previous vertebral
      fracture and a low spine bone mineral density (BMD) (equivalent to a Hologic
      spine T-score below -1.9). The strontium ranelate group had a 41% lower risk of a
      new vertebral fracture than the placebo group over the three-year study period
      (relative risk [RR] = 0.59; 95% confidence interval [CI]: 0.48-0.73; p < 0.001).
      The TROPOS study evaluated non-vertebral fracture prevention in 5091
      postmenopausal women with a mean age of 77 y. The subjects were aged 74 y and
      over (or 70-74 y with one additional risk factor) and a low femoral neck BMD
      (equivalent to an NHANES III [Third National Health and Nutrition Examination
      Survey] T-score below -2.2). Over the three-year study period there was a 16%
      reduction in all non-vertebral fractures (RR = 0.84; 95% CI 0.702-0.995; p =
      0.04) and a 19% reduction at the principal sites for non-vertebral fractures. The
      TROPOS study was not powered to investigate hip fracture risk. However, in a high
      risk group of women aged 74 y and over and with an NHANES III femoral neck T
      score less than -2.4 there was a 36% reduction in hip fracture risk (RR = 0.64;
      95% CI: 0.412-0.997; p = 0.046). The overall incidence of adverse events did not
      differ significantly from placebo and were generally mild and transient, the most
      common being nausea and diarrhea. Strontium ranelate is a useful addition to the
      range of anti-fracture treatments available for treating postmenopausal women
      with osteoporosis and is the only treatment proven to be effective at preventing
      both vertebral and hip fractures in women aged 80 y and over.

PMID- 18046915
TI  - Comparative effects of antiresorptive agents on bone mineral density and bone
      turnover in postmenopausal women.
AB  - Postmenopausal osteoporosis is a common clinical entity; its complications
      represent a significant burden to society. In recent years the choice of
      therapies available for the treatment of postmenopausal osteoporosis has
      increased dramatically. There are a number of antiresorptive agents currently
      available including hormone replacement therapy (HRT), selective estrogen
      receptor modulators (SERMs), bisphosphonates, and dual action bone agents. It is
      difficult to truly compare these therapies given the lack of direct head-to head
      studies. The efficacy of antiresorptive therapies can be assessed in a number of
      ways including measurement of bone mineral density (BMD), assessment of bone
      turnover markers, and fracture reduction. Other important factors include ease of
      administration and consequent patient compliance. This article reviews the
      currently available antiresorptive agents and their effects on the above outcome
      measures.

PMID- 18046916
TI  - Doxazosin in the treatment of benign prostatic hypertrophy: an update.
AB  - We evaluated the efficacy and safety of alpha 1--blocker doxazosin for treatment
      of lower urinary tract symptoms (LUTS) compatible with benign prostatic
      hypertrophy (BPH). Fourteen randomized controlled trials enrolled 6261 men,
      average age 64 years, who had moderately severe LUTS and flow impairment.
      Compared with baseline measures and placebo effect, doxazosin resulted in a
      statistically significant improvement in both LUTS and flow. However, when
      compared with placebo, the average magnitude of symptom improvement
      (International Prostate Symptom Score [IPSS] improvement < 3 points) typically
      did not achieve a level detectable by patients. Combined doxazosin and
      finasteride therapy improved LUTS and reduced the risk of overall clinical
      progression of BPH compared to each drug separately in men followed over 4 years.
      Reported mean changes from baseline in the IPSS were -7.4, -6.6, -5.6, and -4.9
      points for combination therapy, doxazosin, finasteride, and placebo,
      respectively. Combination therapy reduced the need for invasive treatment for BPH
      and the risk of long-term urinary retention. The absolute reductions compared
      with placebo were less than 4% and primarily seen in men with prostate gland
      volume > 40 mL or PSA levels > 4 ng/mL. Efficacy was comparable with other alpha
      1--blockers. Withdrawals from treatment for any cause were comparable to placebo.
      Dizziness and fatigue occurred more frequently with doxazosin compared to
      placebo.

PMID- 18046918
TI  - Patient preference in the management of postmenopausal osteoporosis with
      bisphosphonates.
AB  - The leading treatments for postmenopausal osteoporosis are the nitrogen
      containing bisphosphonates, which are required long term for optimal benefit.
      Oral bisphosphonates have proven efficacy in postmenopausal osteoporosis in
      clinical trials, but in practice the therapeutic benefits are often compromised
      by patients' low adherence. Nonadherence to bisphosphonate therapy negatively
      impacts outcomes such as fracture rate; fractures are in turn associated with
      decreased quality of life. The most common reason cited by patients for their
      nonadherence is that the strict dosing instructions for bisphosphonates are
      difficult to follow. One aspect of bisphosphonate administration that can be
      changed is dosing frequency and several studies have evaluated patient
      preferences for different dosing schedules. Studies have shown a preference for a
      weekly bisphosphonate regimen versus daily dosing and it has been demonstrated
      that this preference for reduced dosing frequency impacts on adherence.
      Ibandronate is the first nitrogen-containing oral bisphosphonate for osteoporosis
      that can be administered in a monthly regimen and two robust clinical studies
      demonstrated a strong patient preference for this monthly regimen versus a weekly
      regimen. It is important that physicians consider patient preference when
      prescribing treatment for osteoporosis to ensure that the disease is effectively
      managed for the long-term benefit of the patient.

PMID- 18046917
TI  - Sildenafil in the treatment of erectile dysfunction: an overview of the clinical
      evidence.
AB  - Erectile dysfunction (ED) is a highly prevalent disease associated with aging as
      well as with several risk factors including hypertension, heart disease, obesity,
      dyslipidemia, diabetes, hypogonadism, drugs-related, and pelvic surgery. Many of
      these factors are components of the metabolic syndrome, a multiplex risk factor
      for cardiovascular disease (CVD). ED shares common risk factors with CVD.
      Endothelial dysfunction seems to be the early underlying pathophysiology across
      both conditions. The efficacy, tolerability and cardiovascular safety of
      sildenafil has been evaluated in numerous large, randomized, doubleblind, placebo
      controlled clinical studies in the broad population of men with ED including men
      with several co-morbid conditions. Sildenafil is effective in several specific
      patient populations including the difficult-to-treat subpopulations such as
      diabetes mellitus and after radical prostatectomy. It is associated with rapid
      onset of action--within 14 minutes for some men--and an extended duration of
      action for up to 12 hours. Sildenafil improves quality of life and satisfaction
      for treated men and is well tolerated with a favorable safety profile. New data
      suggest that sildenafil has beneficial effects in several chronic conditions. It
      has been approved for the treatment of idiopathic pulmonary hypertension.
      Numerous articles have suggested that it improves endothelial function and a
      possible role on premature ejaculation or treatment of lower urinary tract
      symptoms has been suggested.

PMID- 18046919
TI  - Role of 5 alpha-reductase inhibitors in the management of prostate cancer.
AB  - Prostate cancer is one of the most complex and enigmatic oncologic problems in
      medicine. It is highly prevalent, particularly in elderly males. Unfortunately,
      its generally protracted and variable clinical course and high association with
      treatment-related morbidity raise serious questions about the ideal treatment
      strategy for the individual patient. 5 alpha-reductase (5AR) inhibitors have a
      dramatic effect on benign prostatic disease with low toxicity. Thus, there is
      much interest in the potential role of 5AR inhibitors in the prevention and
      treatment of prostate cancer. Finasteride is the only agent that has been shown
      in a randomized clinical trial to decrease the risk of prostate cancer with a
      reduction of almost 25%. Additionally, a recent analysis of the Prostate Cancer
      Prevention Trial (PCPT) has found that finasteride improves the performance
      characteristics of prostate-specific antigen (PSA) blood test as a screening tool
      for prostate cancer, for both cancer detection as well as for detection of high
      risk disease. Finally, 5AR inhibitors have been studied as a component of
      multimodal therapy for all stages of prostate cancer, with the goal of improving
      oncologic outcomes while avoiding the toxicity of medical and surgical
      castration.

PMID- 18046920
TI  - Management of hyperlipidemia with statins in the older patient.
AB  - Numerous randomized, double-blind, placebo-controlled studies and observational
      studies have demonstrated that statins decrease mortality and major
      cardiovascular events in older high-risk persons with hypercholesterolemia. The
      Heart Protection Study found that statins decreased mortality and major
      cardiovascular events in high-risk persons regardless of the initial level of
      serum lipids, age, or gender. The updated National Cholesterol Education Program
      (NCEP) III guidelines state that in very high-risk patients, a serum low-density
      lipoprotein (LDL) cholesterol level of < 70 mg/dl is a reasonable clinical
      strategy, regardless of age. When a high-risk person has hypertriglyceridemia or
      low serum high-density lipoprotein cholesterol, consideration can be given to
      combining a fibrate or nicotinic acid with an LDL cholesterol-lowering drug. For
      moderately high-risk persons (2 or more risk factors and a 10-year risk for
      coronary heart disease of 10% to 20%), the serum LDL cholesterol should be
      decreased to < 100 mg/dl. When LDL cholesterol-lowering drug therapy is used to
      treat high-risk persons or moderately high-risk persons, the serum LDL
      cholesterol should be decreased at least 30% to 40%.

PMID- 18046921
TI  - Tadalafil in the treatment of erectile dysfunction; an overview of the clinical
      evidence.
AB  - Prevalence and severity of erectile dysfunction (ED) increase with aging and are
      often associated with illnesses, like diabetes mellitus, heart disease, and
      hypertension, pathologically characterized by endothelial dysfunction and whose
      prevalence increases with age. The assumption that ED is mainly a neurovascular
      disease is supported by the evidence that specific phosphodiesterase type 5
      (PDE5) inhibition produces an efficient erection in a wide range of ages and
      conditions. The availability of specific PDE5 inhibitors has enabled the
      development of effective treatment strategies, in this contest, tadalafil may be
      considered as the least "typical" PDE5 inhibitor. In clinical trials, tadalafil
      significantly enhanced, in patients of different ages, all efficacy outcomes
      across disease etiologies and severities. With an effectiveness lasting up to
      36h, tadalafil allows patients to choose when to have sexual activities without
      the need to time it, showing positive feedback in terms of quality of life
      related to the treatment. Headache and dyspepsia were the most frequent side
      effects of tadalafil, followed by back pain, nasal congestion, myalgia, and
      flushing, but the impact that long time action could have on effectiveness and
      safety is not yet entirely defined. The aim of this article is to critically
      review the available evidence from the tadalafil clinical research program and
      give the physician a rational approach for intervention in the treatment of ED
      and related diseases.

PMID- 18046923
TI  - Efficacy of language assessment in Alzheimer's disease: comparing in-person
      examination and telemedicine.
AB  - BACKGROUND: With the large number of aging individuals requiring screening of
      cognitive functions for dementing illnesses, there is a necessity for innovative
      evaluation approaches. One domain that should allow for online, at a distance,
      examination is speech and language dysfunction, if the auditory and visual
      transmission is of sufficient quality to allow adequate patient participation and
      reliable, valid interpretation of signs and symptoms (Duffy et al 1997).
      OBJECTIVE: Examine the effectiveness of language assessment in mild Alzheimer's
      patients using telemedicine (TM) compared with traditional in-person (IP)
      assessment. DESIGN: Ten patients with mild Alzheimer's disease, enrolled at a
      Geriatric Memory Clinic received a battery of standard language tests under two
      conditions: face-to-face and via satellite TM. RESULTS: Comparison of TM and IP
      testing conditions were assessed within each for scores on each test in the two
      conditions. On each of the five language tasks, the Wilcoxon signed ranks test
      indicated no significant difference on performance between the TM and IP
      conditions for each participant. Overall acceptance of the TM evaluation in an
      elderly population was rated at a high level except for one individual.
      CONCLUSION: Telemedicine can improve access to speech and language evaluation
      services which is relevant to both dementia and other neurological diseases of
      the elderly. In particular, this specific assessment tool can be used to provide
      evaluations in under-served rural areas.

PMID- 18046922
TI  - Ranibizumab in neovascular age-related macular degeneration.
AB  - Neovascular age-related macular degeneration (AMD) is a visually devastating
      condition resulting from choroidal neovascularization and secondary photoreceptor
      loss. Ranibizumab and bevacizumab are medications that target vascular
      endothelial growth factor (VEGF). While other therapies have demonstrated some
      ability to reduce the risk of losing vision from neovascular AMD, most patients
      continue to lose some degree of central visual acuity. There is growing evidence
      that intravitreal administration of ranibizumab and bevacizumab is effective in
      significantly improving the visual acuity in patients with neovascular age
      related macular degeneration.

PMID- 18046924
TI  - Too many notes: up and down the scales of diabetes therapy.

PMID- 18046925
TI  - Advancing therapy in type 2 diabetes mellitus with early, comprehensive
      progression from oral agents to insulin therapy.
AB  - BACKGROUND: Early and intensive glycemic control is necessary to prevent or
      minimize the development of microvascular and macrovascular complications in
      individuals with type 2 diabetes mellitus. However, many patients are unable to
      attain glycemic control, partly due to protracted treatment with oral
      antidiabetic drugs (OADs) despite inadequate control and barriers to initiating
      insulin therapy. Patients at different stages of disease may benefit from the
      early introduction of intensive glycemic control. OBJECTIVE: This article
      discusses some of the potential barriers to achieving and maintaining optimal
      glycemic levels in patients whose blood glucose is sub-optimally controlled with
      OADs and reviews the benefits of early introduction of intensive glycemic control
      in patients at various stages of disease, with an emphasis on insulin therapy.
      METHODS: Relevant English-language articles published from 1996 to 2006 were
      identified through searches of the National Center for Biotechnology PubMed
      database. Search terms included insulin, insulin therapy, type 2 diabetes,
      insulin analogs, early insulinization, and diabetes prevention, among others.
      Studies were assessed regarding designs, primary and secondary efficacy
      parameters, glycosylated hemoglobin (HbA1c), fasting plasma glucose, incidence of
      hypoglycemia, and other safety assessments. Inclusion criteria were multicenter,
      randomized, open-label, parallel-group trials, as well as retrospective
      observational studies, conducted in Europe or the United States. Additional
      analyses and guideline-based recommendations are included. RESULTS: The landmark
      results of the United Kingdom Prospective Diabetes Study, which found that an
      intensive strategy in 3867 newly diagnosed patients with type 2 diabetes was
      associated with stricter glycemic control than was conventional care (HbA1c over
      10 years, 7.0% vs 7.9%; P < 0.001), as well as a 25% reduction in the risk for
      microvascular complications (P = 0.01). Early initiation of insulin therapy
      concomitantly with OADs appeared well tolerated in the populations studied, was
      effective in recently diagnosed patients, and may also confer anti-inflammatory
      and antiatherogenic effects. Characteristics associated with newer formulations
      of insulin (eg, basal insulin analogues as well as rapid-acting insulin
      analogues, the insulin pump, or inhaled insulin) may help overcome barriers
      associated with initiating insulin therapy. CONCLUSIONS: Based on the literature,
      early and persistent intensification of antidiabetic therapy is an approach that
      most likely will achieve optimal glycemic control in patients with type 2
      diabetes and help prevent associated complications. Greater clinical experience
      with newer therapeutic approaches, including incretin mimetics and dipeptidyl
      peptidase-IV inhibitors, will provide insight into their place in the spectrum of
      diabetes treatments.

PMID- 18046926
TI  - Prandial premixed insulin analogue regimens versus basal insulin analogue
      regimens in the management of type 2 diabetes: an evidence-based comparison.
AB  - BACKGROUND: Insulin is an effective treatment for type 2 diabetes (T2D), a
      progressive condition in which insulin deficiency is one of the core defects.
      When patients with T2D are unable to achieve glycemic goals with diet and oral
      antihyperglycemic medications, a common starting insulin regimen consists of
      basal or premixed insulin added to oral antihyperglycemic medications. When
      glycemic goals are not achieved with the initial insulin regimen, a basal-bolus
      regimen is necessary. OBJECTIVE: This article reviews clinical-trial data on the
      efficacy and safety profile of prandial premixed insulin analogues (insulin
      aspart and insulin lispro) compared with basal insulin analogues (insulin
      glargine, insulin detemir, and insulin lispro protamine suspension), with or
      without a prandial insulin analogue, in the management of T2D. METHODS: A
      systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to
      identify published randomized controlled trials comparing prandial premixed
      insulin analogues with basal insulin analogues, with or without prandial insulin,
      in patients with T2D. The search terms were premixed insulin analogues, premixed
      insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50,
      premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine,
      and detemir. Abstracts presented at the 2005 and 2006 meetings of the American
      Diabetes Association and the European Association for the Study of Diabetes and
      bibliographies of the identified studies were also reviewed. Predetermined
      criteria for study inclusion were treatment duration of at least 12 weeks, T2D
      diagnosed using valid criteria, use of a basal insulin analogue (with or without
      rapid-acting insulin) as a study comparator, and use of well-accepted end points
      (eg, glycosylated hemoglobin [HbA1c], hypoglycemia, preprandial and postprandial
      blood glucose). RESULTS: Of the identified randomized controlled trials, 3
      studies compared premixed insulin analogues containing 70% or 75% basal and 30%
      or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3
      studies evaluated premixed insulin analogues containing 50% basal and 50% rapid
      acting insulin analogue with basal insulin analogues only. Use of prandial
      premixed insulin analogues was associated with better overall and postprandial
      glycemic control. In the studies that compared twice-daily premixed insulin
      analogues with a basal insulin analogue, changes in HbA1c ranged from -1.00% to 
      2.79% and from -0.42% to -2.36%, respectively (P < 0.01). In the studies that
      compared thrice-daily premixed insulin analogues with a basal insulin analogue,
      changes in HbA1c ranged from -0.72% to -1.2% and from -0.3% to -0.75%,
      respectively (P < 0.01). These results were achieved with some increase in
      overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the
      premixed insulin analogues were adjusted during the titration period to achieve
      glycemic goals. CONCLUSIONS: The results of this systematic review suggest that
      regimens consisting of prandial premixed insulin analogues, which provide both
      basal and prandial insulin coverage, may be used as an initial insulin regimen in
      patients with T2D to enable better overall, preprandial, and postprandial
      glycemic control compared with a basal insulin analogue regimen alone. Premixed
      insulin analogues are an effective option for initiating and intensifying insulin
      therapy in patients with T2D.

PMID- 18046927
TI  - Developing a pulmonary insulin delivery system for patients with diabetes.
AB  - BACKGROUND: Many patients with type 1 or type 2 diabetes mellitus (DM) do not
      achieve recommended glycemic goals. Insulin therapy is often delayed, despite its
      effectiveness in maintaining glycemic control, for reasons such as fear of
      needles or dislike of the complexity of injections. Inhaled dry powder insulin
      (IDPI) is approved for preprandial use in both the United States and Europe.
      METHODS: Relevant English-language publications were identified through a search
      of the PubMed database (1980-2007). Search terms included diabetes, in
      combination with subcutaneous and/or inhaled insulin. A similar search of
      abstracts from the 2006 American Diabetes Association 66th Annual Scientific
      Sessions was also performed. RESULTS: Eight clinical studies to date have
      reported that IDPI consistently improved glycemic control, whether used in
      combination with longer-acting SC insulin regimens in patients with type 1 or
      type 2 DM or to supplement or replace oral agent therapy in patients with type 2
      DM. Evidence to date suggests that IDPI is associated with an acceptable
      tolerability profile, with a risk of hypoglycemia similar to that of SC insulin
      (risk ratios in 2 studies were 0.94 and 0.96, in favor of IDPI). Moreover, no
      clinically significant changes in pulmonary function have been noted. Patients
      treated with IDPI in clinical studies reported significantly greater improvements
      in overall satisfaction with treatment compared with SC insulin (P < 0.01) or
      oral agent therapy (P = 0.02). CONCLUSION: IDPI is effective and well tolerated
      for the treatment of diabetes and may be an option for patients to achieve
      glycemic control.

PMID- 18046928
TI  - Importance of observational studies in clinical practice.
AB  - BACKGROUND: In this era of evidence-based medicine, clinicians require a
      comprehensive range of well-designed studies to support prescribing decisions and
      patient management. In recent years, data from observational studies have become
      an increasingly important source of evidence because of improvements in
      observational-study methods and advances in statistical analysis. OBJECTIVE: This
      article reviews the current literature and reports some of the key studies
      indicating that observational studies can both complement and build on the
      evidence base established by randomized controlled trials (RCTs). METHODS: A
      literature search using the MEDLINE/ PubMed database (years: 1966-present) was
      carried out using the search terms observational or observational study(ies),
      historical control, nonrandomized, and postmarketing surveillance. All references
      comparing observational studies with randomized controlled trials were obtained
      and reviewed and were also hand-checked for studies not identified in the
      database searches. RESULTS: Observational studies play an important role in
      investigating treatment outcomes. Data from large observational studies can
      clarify the tolerability profile of marketed medicines. In particular,
      observational studies can be of benefit in the study of large, heterogeneous
      patient populations with complex, chronic diseases such as diabetes mellitus.
      Observational studies have played a key role in supporting the results of Phase
      III studies of insulin analogues for the treatment of patients with type 1 and
      type 2 diabetes. Future observational studies in the field of diabetes such as
      PREDICTIVE (Predictable Results and Experience in Diabetes through
      Intensification and Control to Target: an International Variability Evaluation)
      and IMPROVE will further our understanding of this global pandemic. CONCLUSIONS:
      Well-designed observational studies can play a key role in supporting the
      evidence base for drugs and therapies. Current evidence suggests that
      observational studies can be conducted using the same exacting and rigorous
      standards as are used for RCTs. The observational study design should be
      considered as a complementary rather than a rival analytic technique.

PMID- 18046929
TI  - Health care costs and medication adherence associated with initiation of insulin
      pen therapy in medicaid-enrolled patients with type 2 diabetes: a retrospective
      database analysis.
AB  - BACKGROUND: Clinical, health, and economic outcomes in patients with type 2
      diabetes may be influenced by self-management behaviors and type of
      pharmacotherapy. OBJECTIVE: This study examined differences in medication
      adherence and total health care costs among patients with type 2 diabetes who
      initiated or converted to insulin administration with a pen device in comparison
      with a vial/syringe as add-on therapy to oral antidiabetic drugs. METHODS: This
      study evaluated patients with type 2 diabetes who were enrolled in the North
      Carolina Medicaid program from September 24, 2001, to July 18, 2006. Patients
      receiving insulin with a vial/syringe who converted to pen therapy were compared
      with those who remained on vial/syringe in both unmatched comparisons (n = 560
      and n = 9988, respectively) and after pair-matching (both cohorts, n = 560) with
      the use of propensity scores. In a second analysis, patients who initiated
      insulin with vial/syringe (n = 1162) were compared with a cohort that initiated
      insulin pen therapy (n = 168) after controlling for covariates in a multivariate
      regression model. All included patients had complete enrollment for at least 24
      months of followup. Multiple linear regression models were used to predict the
      comparative impact on total health care costs and medication adherence for each
      cohort. Adjusted means were calculated to determine the group differences for
      each outcome. RESULTS: Diabetes-related and overall medication adherence was
      comparable for patients initiating insulin with a pen versus a syringe (53% vs
      50% and 94% vs 94%, respectively). However, total annualized health care costs
      were significantly lower for patients using pen therapy than for those using a
      syringe ($14,857.42 vs $31,764.78, respectively; P < 0.05). Cost reductions with
      pen therapy were reflected in hospital costs ($1195.93 vs $4965.31, respectively;
      P < 0.05), diabetes-related costs ($7324.37 vs $13,762.21, respectively; P <
      0.05), and outpatient costs ($7795.98 vs $13,103.51, respectively; P < 0.05).
      However, prescription costs of syringe were significantly lower ($535.70 vs
      $670.52; P < 0.05) and costs of pen were higher ($840.33 vs $0; P < 0.05) in
      patients who were switched from syringe to pen versus those who remained on
      syringe therapy. CONCLUSIONS: In a state Medicaid setting among patients with
      type 2 diabetes, initiating insulin therapy with a pen device was associated with
      comparable medication adherence and significant reductions in health care
      resource utilization and associated costs compared with vial/syringe insulin.
      Health care professionals and policy makers should consider the potential
      economic benefits of pen therapy when initiating insulin among Medicaid
      beneficiaries who fail to respond to oral antidiabetic drugs.

PMID- 18046930
TI  - Comparisons of rosiglitazone versus pioglitazone monotherapy introduction and
      associated health care utilization in medicaid-enrolled patients with type 2
      diabetes mellitus.
AB  - BACKGROUND: Outcomes in patients with type 2 diabetes mellitus (DM) can differ
      based on the antidiabetic medication that is used. Thiazolidinediones (TZDs) are
      a newer class of agents used for the treatment of type 2 DM. No previous study
      has compared health care utilization associated with the 2 TZDs on the market.
      OBJECTIVE: The objective of this study was to compare health care utilization and
      costs associated with initiation of treatment with either rosiglitazone or
      pioglitazone by Medicaid-enrolled patients with type 2 DM. METHODS: This was a
      retrospective data analysis comparing cohorts of patients with type 2 DM starting
      a new antidiabetic medication in terms of hospitalizations, emergency department
      visits, outpatient physician visits, and health care costs reimbursed by the
      North Carolina Medicaid program. The perspective adopted in this analysis was
      that of the third-party payer (ie, the North Carolina Medicaid program). Patients
      starting rosiglitazone between July 1, 2001, and June 30, 2002, were compared
      with patients starting pioglitazone during the same period. The patients were
      followed up for 30 months to examine the difference in health care utilization
      over time. Multivariate regression techniques were employed for comparisons
      between the 2 different antidiabetic therapies. RESULTS: A total of 1705 patients
      with type 2 DM were identified and included in the final cohort. There were 660
      patients (mean [SD] age, 49.0 [10.2] years) in the rosiglitazone arm and 1045
      patients (mean [SD] age, 49.1 [10.5] years) in the pioglitazone arm. Multivariate
      analysis showed that the rosiglitazone monotherapy group was associated with a
      12.2% decrease in the mean number of hospitalizations, a 10.4% decrease in the
      mean number of emergency department visits, and a 7.3% decrease in total health
      care costs compared with the pioglitazone monotherapy group (all, P < 0.05). This
      study only looked at patients who used the same drug for the entire follow-up
      period. It did not account for drug switching or addition of a new drug to an
      existing therapy. CONCLUSIONS: Introduction of rosiglitazone was associated with
      a decreased number of hospitalizations, emergency department visits, and total
      health care costs compared with pioglitazone. The utilization of oral
      antidiabetic agents, with documented clinical and economic benefits, should
      continue to be advocated to reduce avoidable medical care utilization and to
      improve patient outcomes in this population.

PMID- 18046931
TI  - Health care costs and mortality for Canadian urban and rural patients with
      diabetes: population-based trends from 1993-2001.
AB  - BACKGROUND: Recent reports suggest that the health status of individuals residing
      in rural areas (as much as one third of the Canadian population) may be inferior
      to those who live in urban areas. OBJECTIVE: This study compared trends in
      mortality and in provincial health care system costs for individuals with
      diabetes, according to urban/rural residence in Saskatchewan, Canada. METHODS:
      The Canadian National Diabetes Surveillance System criteria were applied to the
      linked administrative databases of Saskatchewan Health to identify all
      individuals with diabetes between 1991 and 2001. Annual health care costs across
      5 categories of health care services (physician visits, prescription medications,
      hospitalizations, day surgeries, and dialysis) were identified over a 9-year
      period (1993-2001). Costs (in 2001 Can $) and mortality rates were directly age
      adjusted, and comparisons were made across individuals residing in large urban,
      small urban, and rural areas. RESULTS: A total of 57,774 individuals with
      diabetes were identified, approximately half (n = 26,656) of whom resided in
      rural areas. In 2001, total per capita costs were $3454 for large urban, $3427
      for small urban, and $3289 for rural dwellers. Per capita costs of most
      individual categories were highest in large urban centers over the follow-up
      period with the exception of hospitalizations, which were highest among rural
      residents ($1444 vs $1283 for large urban residents). Despite differences in the
      individual cost categories, overall health care costs according to place of
      residence were similar. Overall, the age-adjusted mortality rates increased
      substantially from 12 (1993) to 18 (2001) deaths per 1000 population, although
      rates were similar across geographic locations. CONCLUSIONS: From 1993 to 2001,
      we observed systematic differences in costs of individual resource categories
      according to urban/rural residence in Saskatchewan, with urban dwellers with
      diabetes incurring greater costs in most categories. Age-adjusted total costs and
      mortality rates were similar, however, suggesting that rural populations with
      diabetes may not be as disadvantaged as commonly believed. Investing in better
      primary care access for all patients with diabetes may reduce downstream costs in
      Saskatchewan's provincial health care system.

PMID- 18046932
TI  - Recognizing and treating excessive sleepiness in primary care.

PMID- 18046933
TI  - Insulin treatment in managing type 2 diabetes: challenges and opportunities.
AB  - Type 2 diabetes is a progressive disease in which diminishing pancreatic beta
      cell failure can induce acute and chronic complications many years prior to
      diagnosis. Therefore, adhering to recommended standards of care and following a
      stepwise approach to the management of type 2 diabetes, with early initiation of
      insulin therapy that ameliorates both fasting and postprandial hyperglycemia, can
      address the progressive increase in insulin resistance and decline in insulin
      secretion. An insulin regimen that introduces basal and prandial doses of insulin
      gradually to sustain daytime glycemic control is both practical and effective.

PMID- 18046934
TI  - Current developments in private offerings.

PMID- 18046935
TI  - Detecting reduced bone mineral density from dental radiographs using statistical
      shape models.
AB  - We describe a novel method of estimating reduced bone mineral density (BMD) from
      dental panoramic tomograms (DPTs), which show the entire mandible. Careful expert
      width measurement of the inferior mandibular cortex has been shown to be
      predictive of BMD in hip and spine osteopenia and osteoporosis. We have
      implemented a method of automatic measurement of the width by active shape model
      search, using as training data 132 DPTs of female subjects whose BMD has been
      established by dual-energy X-ray absorptiometry. We demonstrate that widths
      measured after fully automatic search are significantly correlated with BMD, and
      exhibit less variability than manual measurements made by different experts. The
      correlation is highest towards the lateral region of the mandible, in a position
      different from that previously employed for manual width measurement. An receiver
      operator characterstic (ROC) analysis for identifying osteopenia (T < -1: BMD
      more than one standard deviation below that of young healthy females) gives an
      area under curve (AUC) value of 0.64. Using a minimal interaction to initiate
      active shape model (ASM) search, the measurement can be made at the optimum
      region of the mandible, resulting in an AUC value of 0.71. Using an independent
      test set, AUC for detection of osteoporosis (T < -2.5) is 0.81.

PMID- 18046936
TI  - Bi-Fi: an embedded sensor/system architecture for REMOTE biological monitoring.
AB  - Wireless-enabled processor modules intended for communicating low-frequency
      phenomena (i.e., temperature, humidity, and ambient light) have been enabled to
      acquire and transmit multiple biological signals in real time, which has been
      achieved by using computationally efficient data acquisition, filtering, and
      compression algorithms, and interfacing the modules with biological interface
      hardware. The sensor modules can acquire and transmit raw biological signals at a
      rate of 32 kb/s, which is near the hardware limit of the modules. Furthermore,
      onboard signal processing enables one channel, sampled at a rate of 4000
      samples/s at 12-bit resolution, to be compressed via adaptive differential-pulse
      code modulation (ADPCM) and transmitted in real time. In addition, the sensors
      can be configured to filter and transmit individual time-referenced "spike"
      waveforms, or to transmit the spike height and width for alleviating network
      traffic and increasing battery life. The system is capable of acquiring eight
      channels of analog signals as well as data via an asynchronous serial connection.
      A back-end server archives the biological data received via networked gateway
      sensors, and hosts them to a client application that enables users to browse
      recorded data. The system also acquires, filters, and transmits oxygen saturation
      and pulse rate via a commercial-off-the-shelf interface board. The system
      architecture can be configured for performing real-time nonobtrusive biological
      monitoring of humans or rodents. This paper demonstrates that low-power,
      computational, and bandwidth-constrained wireless-enabled platforms can indeed be
      leveraged for wireless biosignal monitoring.

PMID- 18046937
TI  - Privacy-preserving telecardiology sensor networks: toward a low-cost portable
      wireless hardware/software codesign.
AB  - Recently, a remote-sensing platform based on wireless interconnection of tiny ECG
      sensors called Telecardiology Sensor Networks (TSN) provided a promising approach
      to perform low-cost real-time cardiac patient monitoring at any time in community
      areas (such as elder nursing homes or hospitals). The contribution of this
      research is the design of a practical TSN hardware/software platform for a
      typical U.S. healthcare community scenario (such as large nursing homes with many
      elder patients) to perform real-time healthcare data collections. On the other
      hand, due to the radio broadcasting nature of MANET, a TSN has the risk of losing
      the privacy of patients' data. Medical privacy has been highly emphasized by U.S.
      Department of Health and Human Services. This research also designs a medical
      security scheme with low communication overhead to achieve confidential
      electrocardiogram data transmission in wireless medium.

PMID- 18046938
TI  - An automated methodology for fetal heart rate extraction from the abdominal
      electrocardiogram.
AB  - This paper introduces an automated methodology for the extraction of fetal heart
      rate from cutaneous potential abdominal electrocardiogram (abdECG) recordings. A
      three-stage methodology is proposed. Having the initial recording, which consists
      of a small number of abdECG leads in the first stage, the maternal R-peaks and
      fiducial points (QRS onset and offset) are detected using time-frequency (t-f)
      analysis and medical knowledge. Then, the maternal QRS complexes are eliminated.
      In the second stage, the positions of the candidate fetal R-peaks are located
      using complex wavelets and matching theory techniques. In the third stage, the
      fetal R-peaks, which overlap with the maternal QRS complexes (eliminated in the
      first stage) are found using two approaches: a heuristic algorithm technique and
      a histogram-based technique. The fetal R-peaks detected are used to calculate the
      fetal heart rate. The methodology is validated using a dataset of eight short and
      ten long-duration recordings, obtained between the 20th and the 41st week of
      gestation, and the obtained accuracy is 97.47%. The proposed methodology is
      advantageous, since it is based on the analysis of few abdominal leads in
      contrast to other proposed methods, which need a large number of leads.

PMID- 18046939
TI  - Delivering a lifelong integrated electronic health record based on a service
      oriented architecture.
AB  - Efficient access to a citizen's Integrated Electronic Health Record (I-EHR) is
      considered to be the cornerstone for the support of continuity of care, the
      reduction of avoidable mistakes, and the provision of tools and methods to
      support evidence-based medicine. For the past several years, a number of
      applications and services (including a lifelong I-EHR) have been installed, and
      enterprise and regional infrastructure has been developed, in HYGEIAnet, the
      Regional Health Information Network (RHIN) of the island of Crete, Greece.
      Through this paper, the technological effort toward the delivery of a lifelong I
      EHR by means of World Wide Web Consortium (W3C) technologies, on top of a service
      oriented architecture that reuses already existing middleware components is
      presented and critical issues are discussed. Certain design and development
      decisions are exposed and explained, laying this way the ground for coordinated,
      dynamic navigation to personalized healthcare delivery.

PMID- 18046940
TI  - Knowledge-based data analysis: first step toward the creation of clinical
      prediction rules using a new typicality measure.
AB  - Clinical prediction rules play an important role in medical practice. They
      expedite diagnosis and limit unnecessary tests. However, the rule creation
      process is time consuming and expensive. With the current developments of
      efficient data mining algorithms and growing accessibility to medical data, the
      creation of clinical rules can be supported by automated rule induction from
      data. A data-driven method based on the reuse of previously collected medical
      records and clinical trial statistics is cost-effective; however, it requires
      well defined and intelligent methods for data analysis. This paper presents a new
      framework for knowledge representation for secondary data analysis and for
      generation of a new typicality measure, which integrates medical knowledge into
      statistical analysis. The framework is based on a semiotic approach for
      contextual knowledge and fuzzy logic for approximate knowledge. This semio-fuzzy
      framework has been applied to the analysis of predictors for the diagnosis of
      obstructive sleep apnea. This approach was tested on two clinical data sets.
      Medical knowledge was represented by a set of facts and fuzzy rules, and used to
      perform statistical analysis. Statistical methods provided several candidate
      outliers. Our new typicality measure identified those, which were medically
      significant, in the sense that the removal of those important outliers improved
      the descriptive model. This is a critical preprocessing step towards automated
      induction of predictive rules from data. These experimental results demonstrate
      that knowledge-based methods integrated with statistical approaches provide a
      practical framework to support the generation of clinical prediction rules.

PMID- 18046941
TI  - An integrated system for the segmentation of atherosclerotic carotid plaque.
AB  - In this paper, we propose and evaluate an integrated system for the segmentation
      of atherosclerotic plaque in ultrasound imaging of the carotid artery based on
      normalization, speckle reduction filtering, and four different snakes
      segmentation methods. These methods are the Williams and Shah, Balloon, Lai and
      Chin, and the gradient vector flow (GVF) snake. The performance of the four
      different plaque snakes segmentation methods was tested on 80 longitudinal
      ultrasound images of the carotid artery using receiver operating characteristic
      (ROC) analysis and the manual delineations of an expert. All four methods were
      very satisfactory and similar in all measures evaluated, with no significant
      differences between them; however, the Lai and Chin snakes segmentation method
      gave slightly better results. Concluding, it is proposed that the integrated
      system investigated in this study could be used successfully for the automated
      segmentation of the carotid plaque.

PMID- 18046942
TI  - A computational framework for approximating boundary surfaces in 3-D biomedical
      images.
AB  - We propose a new method for detecting and approximating the boundary surfaces in
      three-dimensional (3-D) biomedical images. Using this method, each boundary
      surface in the original 3-D image is normalized as a zero-value isosurface of a
      new 3-D image transformed from the original 3-D image. A novel computational
      framework is proposed to perform such an image transformation. According to this
      framework, we first detect boundary surfaces from the original 3-D image and
      compute discrete samplings of the boundary surfaces. Based on these discrete
      samplings, a new 3-D image is constructed for each boundary surface such that the
      boundary surface can be well approximated by a zero-value isosurface in the new 3
      D image. In this way, the complex problem of reconstructing boundary surfaces in
      the original 3-D image is converted into a task to extract a zero-value
      isosurface from the new 3-D image. The proposed technique is not only capable of
      adequately reconstructing complex boundary surfaces in 3-D biomedical images, but
      it also overcomes vital limitations encountered by the isosurface-extracting
      method when the method is used to reconstruct boundary surfaces from 3-D images.
      The performances and advantages of the proposed computational framework are
      illustrated by many examples from different 3-D biomedical images.

PMID- 18046943
TI  - A radio frequency identification implanted in a tooth can communicate with the
      outside world.
AB  - A radio frequency identification (RFID) transponder covering the 13.56 MHz band
      was adapted to minimize its volume so that it could be placed in the pulp chamber
      of an endodontically treated human tooth. The minimized transponder had a maximum
      communication distance of 30 mm. In an animal experiment, the transponder was
      fixed in the cavity of a mandibular canine of a dog. An RFID reader positioned
      close to the dog's face could communicate with the transponder in the dog's
      tooth. In certain cases, the system is applicable for the personal identification
      procedures for hospitalized patients instead of an identification wristband.

PMID- 18046944
TI  - Do you know tobacco's effect on your state?

PMID- 18046945
TI  - Clearing the air. An update on the progress of tobacco control.

PMID- 18046946
TI  - What programs does your institution offer for tobacco cessation? St. Louis
      University provides programs for employees, patients, and the public.

PMID- 18046947
TI  - What strategies have you found to be effective in helping patients to stop
      smoking?

PMID- 18046948
TI  - Working holiday shifts may be difficult, but Heather remains thankful.

PMID- 18046949
TI  - Intracellular signaling protein may be involved in cancer-promoting inflammation.

PMID- 18046950
TI  - Manage skin toxicities associated with targeted therapies.

PMID- 18046951
TI  - Contemplating complementary medicine?

PMID- 18046952
TI  - Baumol's disease.

PMID- 18046953
TI  - Payer trend: 'tiering' physicians and 'steering' patients.

PMID- 18046954
TI  - Panel size: answers to physicians' frequently asked questions.

PMID- 18046955
TI  - The makings of a good meeting.

PMID- 18046956
TI  - Optimizing referrals & consults with a standardized process.

PMID- 18046957
TI  - Aiding the wounded among us.

PMID- 18046958
TI  - Inosine monophosphate dehydrogenase as a probe in antiviral drug discovery.
AB  - Inosine monophosphate (IMP) dehydrogenase (IMPDH) is a significant enzyme in the
      purine nucleotide biosynthetic pathway. IMPDH is viewed as an important
      biological target in the quest for drugs in the antiviral therapeutic area. This
      review article is focused on the chemistry and biology of IMPDH inhibitors and
      the use of IMPDH inhibition data as a probe in antiviral drug discovery. Examples
      of both inosine 5' monophosphate and NAD+ site-directed inhibitors are presented.
      Correlation of antiviral activities with IMPDH inhibition is discussed.

PMID- 18046959
TI  - The structure-activity relationships of 2,4(1H,3H)-pyrimidinedione derivatives as
      potent HIV type 1 and type 2 inhibitors.
AB  - Since the discovery of the 2,4 (1H,3H)-pyrimidinediones as potent non-nucleoside
      inhibitors of the HIV-1 reverse transcriptase (RT) this class of compounds has
      yielded a number of N-1 acyclic substituted pyrimidinediones with substantial
      antiviral activity, which is highly dependent upon their molecular fit into the
      binding pocket common to this inhibitory class. We have specifically examined the
      structure activity relationships of compounds with chemical modification made by
      substituting homocyclic rather than acyclic moieties at N-1 of the
      pyrimidinedione. Seventy-four compounds were synthesized and evaluated for
      antiviral activity against HIV-1 and HIV-2. The homocyclic modifications resulted
      in compounds with significant activity against both HIV-1 and HIV-2, suggesting
      these compounds represent a new class of non-nucleoside RT inhibitors. The
      structure-activity relationship (SAR) evaluations indicated that cyclopropyl,
      phenyl and 1- or 3-cyclopenten-1-yl substitutions at the N-1 of the
      pyrimidinedione, the addition of a methyl linker between the cyclic moiety and
      the N-1 and the addition of a benzoyl group at the C-6 of the pyrimidinedione had
      the greatest contribution to antiviral activity. Five pyrimidinedione analogues
      with therapeutic indexes (TIs) > 450,000 and a specific analogue (1
      cyclopropylmethyl-5-isopropyl-6-(3,5-dimethylbenzoyl)-2,4(1H,3H)
      pyrimidinedione), which exhibited a TI of > 2,000,000, were identified. None of
      the analogues were cytotoxic to target cells at the highest in vitro test
      concentration, which is the upper limit of compound solubility of the analogues
      in aqueous solution. Thus, we have identified a series of pyrimidinediones with
      substantially improved antiviral efficacy and range of action and with
      significantly reduced cellular cytotoxicity.

PMID- 18046960
TI  - Isothiazole derivatives as antiviral agents.
AB  - We recently described the synthesis and antiviral activity of the compounds 5
      phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-isothiazolecarbonitrile
      and S-(4-cyano-5-phenylisothiazol -3-yl)-O-ethyl thiocarbonate, which were found
      to be effective against both HIV-1 (IIIB) and HIV-2 (ROD). We have now evaluated
      these compounds against both RNA and DNA viruses, obtaining high selectivity
      indexes for poliovirus 1 (SI: 223 and 828, respectively) and Echovirus 9 (SI: 334
      and 200, respectively). In our previous studies, 3-methylthio-5-(4-OBn-phenyl)-4
      isothiazolecarbonitrile was found to exhibit a broad spectrum of action against
      picornaviruses, we therefore selected this compound and S-(4-cyano-5
      phenylisothiazol-3-yl)-O-ethyl thiocarbonate as the model for the synthesis of a
      new isothiazole derivative, S-[4-cyano-5-(4-OBn-phenyl)isothiazol-3-yl]-O-ethyl
      thiocarbonate. This compound was evaluated against picornaviruses, measles virus,
      HIV-1 (IIIB) and HIV-2 (ROD), and some DNA viruses (adenovirus type 2 and herpes
      simplex virus type 1). The compound was shown to be active against rhinoviruses
      2, 39, 86 and 89, Coxsackie B1 and measles virus.

PMID- 18046961
TI  - Profound anti-HIV-1 activity of DAPTA in monocytes/macrophages and inhibition of
      CCR5-mediated apoptosis in neuronal cells.
AB  - Monocytes/macrophages (M/M) are strategic reservoirs of HIV-1, spreading the
      virus to other cells and inducing apoptosis in T-lymphocytes, astrocytes and
      neurons. M/M are commonly infected by R5 HIV-1 strains, which use the chemokine
      receptor CCR5. D-Ala-peptide T-amide (DAPTA), or Peptide T, named for its high
      threonine content (ASTTTNYT), is a synthetic peptide comprised of eight amino
      acids (185-192) of the gp120 V2 region and functions as a viral entry inhibitor
      by targeting selectively CCR5. The anti-HIV-1 activity of DAPTA was evaluated in
      M/M infected with R5 HIV-1 strains. DAPTA at 10(-9) M inhibited HIV-1 replication
      in M/M by > 90%. PCR analysis of viral cDNA in M/M showed that DAPTA blocks HIV
      entry and in this way prevents HIV-1 infection. Moreover, DAPTA acts as a strong
      inhibitor and was more active than the non-peptidic CCR5 antagonist TAK-779 in
      inhibiting apoptosis (mediated by RS HIV-1 strains produced and released by
      infected M/M) on a neuroblastoma cell line. Our results suggest that antiviral
      compounds which interfere with receptor mechanisms such as CCR5 could be
      important, either alone or in combination with other antiretroviral treatments,
      in preventing HIV infection in the central nervous system and the consequential
      neuronal damage that leads to neuronal AIDS.

PMID- 18046962
TI  - A comparison of the phenotypic susceptibility profiles of emtricitabine and
      lamivudine.
AB  - Emtricitabine (FTC) and lamivudine (3TC) are cytosine nucleoside analogues
      approved for use in HIV-1 infection. Both compounds select for the M184V/I
      mutation resulting in high-level resistance. This study compared the phenotypic
      resistance profiles of FTC and 3TC. Both compounds were tested against clinical
      samples submitted for routine resistance testing (PhenoSense HIV assay). We
      evaluated 306 viruses with nucleoside reverse transcriptase inhibitor mutations
      (NRTI-R) and 100 viruses without resistance mutations (WT). Seventy-two percent
      had > or = 1 thymidine analogue mutation (TAM), 21% had mixtures at M184, 14% had
      L74V and 7.5% had K65R. Results were expressed as fold change (FC) in 50%
      effective concentration compared with the NL4-3 reference. Concordance of FC was
      evaluated based on biological (99th percentile of the distribution of WT virus
      population) and clinical cutoffs (FC above which an optimal virological response
      declines). Against the WT viruses, FTC and 3TC had identical mean FC values
      relative to the NL4-3 reference of 0.9-fold +/- 0.2 and identical biological
      cutoffs of 1.4-fold against WT viruses. For NRTI-R isolates, there was a strong
      linear correlation between FTC and 3TC FC values (r2 = 0.94). Moreover, there was
      > 90% concordance in resistance calls based on either the biological (1.4-fold)
      or proposed clinical (3.5-fold) cutoffs among all NRTI-R isolates or isolates
      with M184V/I mixtures. In the absence of M184V/I, the majority of samples with
      resistance (> 3.5 FC) exhibited TAMs with a trend toward increased levels of
      cross-resistance with increasing numbers of TAMs. FTC and 3TC demonstrate nearly
      identical phenotypic resistance profiles and have the same biological cutoff in
      this panel of NRTI-R and WT clinical HIV-1 isolates.

PMID- 18046963
TI  - Novel 3-sulphonamido-quinazolin-4(3H)-one derivatives: microwave-assisted
      synthesis and evaluation of antiviral activities against respiratory and
      biodefense viruses.
AB  - We designed and synthesized novel 2,3-disubstituted quinazolin-4(3H)-ones by
      microwave technique and characterized them by spectral analysis. Synthesized
      compounds were screened for cytotoxicity and for antiviral activity against
      influenza A (H1N1, H3N2 and H5N1), severe acute respiratory syndrome corona,
      dengue, yellow fever, Venezuelan equine encephalitis (VEE), Rift Valley fever,
      and Tacaribe viruses in cell culture. A neutral red uptake assay was used to
      determine 50% virus-inhibitory concentrations (EC50) of test compounds and their
      50% cytotoxicity concentration (CC50) in uninfected Madin-Darby canine kidney,
      Vero, and Vero 76 cells; selectivity indices (ratio of CC50 to EC50) were derived
      from the data. The compound 4-(6,8-dibromo-4-oxo-2-phenyl quinazolin-3(4H)-yl)-N
      (4,5-dimethyloxazol-2yl) benzenesulphonamide 15 inhibited the replication of
      avian influenza (H5N1) virus (EC50 = 8.4 microg/ml, CC50 > 100 microg/ml, SI >
      11.9) as did 4-(6-bromo-4oxo-2phenylquinazolin-3(4H)-yl) benzene]sulphonamide 5
      (EC50 = 3 microg/ml, CC50 = 32 microg/ml, SI = 11). Compound 5 was also
      moderately active against VEE and Tacaribe viruses. The methodology described in
      this report is applicable for rapid synthesis of many compounds with potential
      antiviral properties.

PMID- 18046964
TI  - Effect of transdermic acetylsalicylic acid on hemostasis in healthy volunteers.
AB  - Acetylsalicylic acid (ASA) exerts an antiaggregatory effect on platelets by
      irreversible inhibition of the enzyme thrombocyte cyclooxigenase when it is
      administered orally at doses above 80 mg/day. For several years ASA has been
      available as a solution that can be topically applied on the skin. It is widely
      used by athletes and individuals with chronic rheumatic disorders. However, it
      has not been established to date whether the plasma levels that result from these
      doses of ASA affect hemostasis during odontological procedures that involve
      bleeding, causing platelet dysfunction. The aim of the present study was to
      evaluate whether topical application is capable of affecting hemostasis. Three
      studies were conducted: A, B y C. Each of the 3 groups included 12 healthy
      volunteers of both sexes. The aim of study A was to evaluate if the formulation
      for topical application resulted in plasma levels of ASA that resembled those
      observed for the oral formulation and affect hemostasis. In experiment A, plasma
      levels of salicylic acid (SA) were assessed for each volunteer at 30 minutes, 60
      minutes, 6 hours, 12 hours and 24 hours after oral administration of a dose of
      500 mg ASA. Experiment B was identical to experiment A except for the fact that
      ASA was topically applied employing a commercial preparation Aspirub in a
      predetermined area at a rate of 2 ml/day over a period of 15 days. Experiment C
      was designed in the same way as experiment B, for a higher dose and a longer
      period of time (4 ml/day over a period of 30 days). One of the volunteers
      exhibited detectable salicylemia that could affect hemostasis as occurs with the
      oral formulation. The following two studies (C1 and C2) employed doses of Aspirub
      of 8 and 16 ml/day respectively, over a period of 30 days. We measured
      biochemical parameters associated to platelet function. The dose of 8 ml/day
      induced moderate alterations in all the parameters related to platelet function
      and the daily dose of 16 ml inhibited platelet aggregation in all the volunteers
      involved.

PMID- 18046965
TI  - Urinary fluoride excretion in children aged 3 to 5 years exposed to fluoridated
      salt at 60 to 90 mgF/Kg in two Venezuelan cities. A pilot study.
AB  - The aim of the present work was to obtain information on the total urinary
      fluoride concentration and excretion of Venezuelan children at the age of 3 to 5
      years, as part of a program to monitor fluoride ingestion. A 24 hour urine sample
      was collected from each of 63 children, between 3 and 5 years of age and analyzed
      for (i) total urinary volume (ml), (ii) urinary flow rate (ml/h), (iii) fluoride
      concentration (ppm) and (iv)fluoride excretion rate (microg/h). The group
      comprised 32 boys and 31 girls who resided in two different communities, 32 in
      Caracas, DC and 31 in San Juan de los Morros, Guarico state. Fluoride analyses
      were done with an ion-specific electrode. Age and gender did not affect total
      urine volume, urinary flow rate, or urinary fluoride concentration and excretion
      rate. The children from San Juan de los Morros had a significantly higher total
      urinary volume (426.45 +/- 36.31 ml) and flow rate (17.09 +/- 1.57ml/h) than
      children from Caracas (297.06 +/- 23.59 ml and 12.40 +/- 0.98, respectively)
      (p=0.0039). Significant differences were also observed when the urinary fluoride
      excretion rate of the two communities was compared. Mean urinary fluoride
      concentrations did not differ significantly (p < 0.05) between the two
      communities. These values were 0.67 +/- 0.40, 0.57 +/- 0.34, 0.76 +/- 0.27 ppmF
      in the 3, 4 and 5 year-old children of Caracas and 0.69 +/- 0.33, 0.65 +/- 0.20,
      0.63 +/- 0.36 mgF in San Juan de los Morros children. The results showed low
      urinary fluoride concentration and excretion, indicating that children residing
      in the evaluated communities are receiving fluoride below the recommended optimal
      range.

PMID- 18046966
TI  - Subgingival distribution of yeast and their antifungal susceptibility in
      immunocompetent subjects with and without dental devices.
AB  - Yeasts colonize the subgingival biofilm, which becomes a reservoir that favors
      their reproduction. The purpose of the present work was to determine the
      prevalence of yeasts of the Candida genus in the subgingival biofilm of
      gingivoperiodontal disease patients, including users and non-users of dental
      devices, and their susceptibility to fluconazole and voriconazole. Samples of
      subgingival pockets of immunocompetent nonsmokers showing gingivitis and
      periodontitis were inoculated in a differential chromogenic medium. Sixty three
      percent of subjects used dental devices. Yeasts were identified and
      susceptibility to fluconazole and voriconazole was tested following CLSI M44-A
      standards. The prevalence of yeasts in the subgingival biofilm was 40% CI 95%
      (30.5-50.3); 10% were patients who did not use dental appliances. The most
      frequently observed yeasts were C. albicans, and C. parapsilosis, C.
      dubliniensis, C. tropicalis and C. guilliermondii. Only C. dubliniensis and C.
      guilliermondii showed resistance to azoles. The use of dental devices
      significantly increased the prevalence of yeasts in periodontal pockets
      inpatients presenting gingivitis. It is noteworthy that non albicans Candida
      species, such as C. dubliniensis and C. guilliermondii, considered emerging
      species, which have a diminished susceptibility to antifungal agents were found
      in the crevicular fluid of immunocompetent patients.

PMID- 18046967
TI  - Meta-analysis of the literature on 1946 cases of minor salivary gland tumors of
      the palate.
AB  - Minor salivary gland tumors are relatively rare and exhibit great diversity in
      terms of histopathology, localization, biological behavior and classification.
      The studies of significant case series report controversial data, mainly in terms
      of the proportion of benign versus malignant tumors and the relative frequency of
      histological types. Palate tumors are the most frequent, with an incidence of
      over 50%. The aim of the present study was to perform a meta-analysis to evaluate
      salivary gland tumors of the palate in terms of the proportion of malignant
      versus benign tumors, the frequency of the histological types and the data
      employed for statistical analysis. We analyzed a selection of international
      publications (1950-1999) of case series of minor salivary gland tumors of the
      palate, including our own series. The host institutions were classified into 3
      categories: A) High Complexity Institutions (HCI), i.e. oncological reference
      centers and general hospitals that treat cancer patients; B) Medium Complexity
      Institutions (MCI); C) Low Complexity Institutions (LCI). Based on the main
      classifications, we joined categories and employed a simplified classification to
      analyze a total of 1835 cases in the literature and our own series of 111 cases
      (unpublish data). The results of the meta-analysis of the literature demonstrated
      that the data employed for statistical analysis depends on the type of host
      institution. The classification of institutions according to their level of
      complexity allowed for adequate interpretation of the previously published
      statistical data. Our interpretation of these studies suggests that the data on
      the percentage of malignant versus benign tumors and diversity of histological
      type must be obtained from series of low complexity institutions. LCI data are
      reliable whereas the HCI data are based on pre-selected cases, rendering the data
      unreliable.

PMID- 18046968
TI  - Use of radiographs for periodontal diagnosis in private practice.
AB  - The aim of the present study was to determine the percentage of dentists who use
      radiographic examination on the initial appointment, and establish the relation
      between the use of periodontal probe and graduation year. Dentists were
      interviewed in their private offices in three cities in Rio Grande do Sul. They
      were asked about the routine use of radiographic examination and, if applicable,
      what technique was applied and what clinical instrument was used at the first
      appointment. Opened and closed questions were included in the interview and for
      some of them more than one answer was possible. A significant number of dentists
      (62.9%) reported some kind of radiographic examination at the initial
      appointment. Among the radiographic techniques, the periapical was the most cited
      (74.3%), followed by the panoramic (36.2%) and bite-wing (32.9%) techniques.
      There was an association between the use of periodontal probe and the use of
      radiographic examination at the initial appointment. Dentists who used
      periodontal probe used radiographic examination more frequently (p=0.010). More
      recently graduated dentists (1991-2005) used radiographic examination more than
      the others (p=0.022). In conclusion, a large number of dentists reported the use
      of radiographic examination at the initial appointment. There was an association
      between the use of this examination technique and the use of the periodontal
      probe; recently graduated dentists used radiographic examinations more frequently
      than the others.

PMID- 18046969
TI  - Periodontal treatment needs in Argentine adult subjects.
AB  - The aim of the present study was to assess the periodontal treatment needs of the
      population that spontaneously sought treatment from general dentists. 3694
      patients (2000 females and 1494 males, age range between 18 and 84 years) were
      evaluated using the Community Periodontal Index (CPI). Data were reported
      according to the percentage of subjects with the highest Score: 14.3% presented
      pocket depth > or = 5.5 mm (Score 4), 26.4% pocket depth between 3.5 and 5.5
      (Score 3), 38.3% presented pockets < or = 3.5 mm with calculus or overhanging
      restorations (Score 2), 17.2% pockets < or = 3.5 mm with bleeding upon probing
      without calculus (Score 1) and 3.2% were healthy (Score 0). Analyzing the data
      according to age it was observed that in the group > 40 years the percentage of
      patients with Score 4 was higher (25.1%) compared to the other two groups of 18
      34 years (6.4%) and 34-45 years (14.3%). Only 16.4% of the patients consulted for
      periodontal reasons (gingival bleeding or tooth mobility), whereas 88% requested
      treatment for other reasons (pain, caries, esthetics, replacement of teeth,
      etc.). However 77% of the patients in this last group needed periodontal
      treatment. 96.8% of the patients attending the general dentistry office needed
      periodontal treatment: 17.2% oral hygiene instruction, 65.2% oral hygiene
      instruction and scaling and 14.3% complex treatment.

PMID- 18046970
TI  - Development of an intraoral device for facial muscle retraining and its clinical
      application.
AB  - The aim of this work was to develop a facial neuromuscular retraining technique
      for cases of facial palsy, involving an easy-to use intraoral device that allows
      correcting abnormal neuromuscular patterns and improving esthetics. Facial palsy
      is a motor alteration of multiple origin that results in facial asymmetry.
      Treatment remains controversial to date and includes, surgical anastomosis and
      decompressive and plastic surgery, corticosteroids therapy, injection of
      botulinum toxin, and administration of other medicinal drugs. Physical therapy
      involving electrical stimulation and feedback are also used to retrain facial
      muscles. A removable thermopolymerized acrylic intraoral device with wrought wire
      clasps was developed and constructed. The device was used on a patient with
      facial palsy who was instructed to wear it 4 times a day during 20 minutes and
      perform exercises in front of the mirror, trying to coordinate the action of the
      device with the smile movement on the unaffected side of the face. Digital
      photographs of the patient were taken during smile movement and at rest with and
      without the device, and movements of the oral commissures were compared using
      specific software. Results showed anatomic and nonanatomic indices of facial
      motion for the lower part of the face with the device to be 1.77 and 0
      respectively. The device improved facial symmetry during rest by opposing
      traction forces of the contralateral muscles, resulting in a better position of
      the filtrum during rest, and allowed the patient to exercise smile movements at
      home.

PMID- 18046971
TI  - Evaluation of nucleolar organizer regions in maxillary osteosarcoma.
AB  - Maxillary osteosarcomas are a relatively frequent malignant tumor of the oral
      cavity. Similarly to other skeletal osteosarcomas, they exhibit different
      cellular differentiation patterns, i.e. chondroblastic, osteoblastic, or
      fibroblastic. Although their histological features resemble those of
      osteosarcomas of the long bones, their pattern of evolution usually differs.
      Morphometric variations in silver stained Nucleolar Organizer Regions (AgNOR)
      have proved of value to study the biology of several tumors. However, information
      on the analysis of AgNOR in maxillary tumors is scarce. The aim of the present
      study was to analyze the variations of different morphological parameters related
      to AgNOR in a series of 32 cases of maxillary osteosarcoma. In each case we
      analyzed 100 nuclei corresponding to the prevalent cellular differentiation type,
      selecting the most aggressive area. We employed software previously developed at
      our laboratory that yields information on different AgNOR-related parameters. The
      results were compared with those previously reported in a study on 12 cases of
      osteosarcoma of long bones. Six cases of oral mucosa squamous cell carcinoma were
      also included for comparative purposes. Single AgNOR volume proved to be the most
      discriminatory and informative parameter. The value of single AgNOR volume was
      considerably lower in mandible osteosarcomas than in osteosarcomas of the upper
      maxilla (p=0.02). The values were significantly lower in maxillary osteosarcomas
      than in long bone osteosarcomas and in oral carcinomas. This finding would
      suggest a slower rate of cell activity in maxillary osteosarcomas, associated in
      turn to its known lower degree of aggressiveness. The present results suggest
      that the analysis of AgNOR is a valuable and easily applicable marker to
      determine the degree of malignancy and biology of maxillary osteosarcomas.

PMID- 18046972
TI  - The evolution of ACE inhibition--a turning point in cardiovascular medicine.

PMID- 18046973
TI  - Comparison of home and office blood pressure in hypertensive patients treated
      with zofenopril or losartan.
AB  - In a parallel double-blind multicentre study, 375 hypertensive patients were
      enrolled and treated with either the angiotensin-converting enzyme inhibitor
      (ACEI) zofenopril 30 mg once daily (titration 60 mg od) or the angiotensin II
      type 1 receptor (AT1) antagonist losartan 50 mg od (titration 100 mg od).
      Patients with mild to moderate hypertension, defined as a diastolic blood
      pressure (DBP) between 95 and 110 mmHg in the sitting position without other
      signs of cardiovascular disease were enrolled and treated for 12 weeks. BP was
      assessed in the clinic, and self-measured by the patients at home during a
      working day and a holiday, as well as before and at the clinic follow-ups.
      Systolic (SBP) and DBP were significantly reduced in both treatment groups to a
      similar extent at the end of the 12-week study. However, the immediate or early
      reduction of DBP as well as DBP reduction over the first month was significantly
      greater with zofenopril (p= 0 .01 and p= 0 .003, respectively) compared with
      losartan treatment. After 3 months of treatment and dose up-titration, clinic BP
      reductions were similar in both groups. However, more subjects with losartan had
      used a higher dose step (42.1%) compared with zofenopril (33.1%). Home BP
      assessments demonstrated that systolic and diastolic pressures were substantially
      lower than the BP measurements made by sphygmomanometer in the clinic. In
      particular, assessments 2-3 days before the clinic visits during working days and
      holidays were characteristically lower, while the measurements during the clinic
      visits were largely similar to the conventional BP measurements by the doctor.
      The number and the severity of adverse events, related to the study medications,
      were largely benign and similar in both groups. The present study demonstrates
      that zofenopril in clinically recommended doses is at least therapeutically
      equivalent to losartan treatment, when assessed by conventional sphygmomanometry
      at the doctor's office or at home by self-measured BP assessments by the
      patients. Zofenopril however, induces a more rapid initial lowering of BP over
      the first month of therapy.

PMID- 18046974
TI  - An evaluation of the initial and long-term antihypertensive efficacy of
      zofenopril compared with enalapril in mild to moderate hypertension.
AB  - Angiotensin-converting enzyme inhibitors (ACEIs) are used in the management of a
      range of cardiovascular disorders and are well established in primary as well as
      secondary cardiovascular prevention programmes. Over the years, several second-
      and third-generation ACEIs have been introduced into the clinic. In a comparative
      study in patients with mild to moderate hypertension, the efficacy and safety of
      zofenopril 30 mg od (with an up-titration to 60 mg od after 4 weeks in non
      responder patients) was compared with enalapril 20 mg od (with an up-titration to
      40 mg od after 4 weeks in nonresponders) during 12 weeks of treatment. Both
      treatments significantly reduced systolic (SBP) and diastolic blood pressure
      (DBP). BP reduction was significantly greater with zofenopril (30 mg/day) during
      the initial 4 weeks of treatment compared with enalapril (20 mg/day). A larger
      proportion of patients needed dose up-titration with enalapril compared with
      zofenopril to reach preset BP goals. After 12 weeks of treatment and after
      appropriate dose up-titration, SBP and DBPs were lowered to similar extent in the
      two treatment groups, resulting in no differences between the groups in terms of
      response and control rates. A similar number of patients reported adverse events
      in the two study groups. However, the severity of adverse events were
      significantly milder with zofenopril compared with enalapril. In mild to moderate
      hypertensive patients, zofenopril treatment results in a more pronounced lowering
      of BP compared with enalapril at recommended dose levels. Additionally, at
      clinical and comparative antihypertensive doses, zofenopril presents a more
      beneficial adverse event profile compared with enalapril.

PMID- 18046975
TI  - Blood pressure control and response rates with zofenopril compared with
      amlodipine in hypertensive patients.
AB  - Angiotensin-converting enzyme inhibitors (ACEIs) and calcium antagonists are
      today extensively used as first-line monotherapy as well as appropriate
      combination therapy in mild to moderate hypertension. In a parallel-group study,
      using clinically recommended doses, the ACEI zofenopril was compared with the
      calcium antagonist amlodipine in respect of their antihypertensive properties. In
      the study, 303 hypertensive patients, aged 18-75 years, were compared in terms of
      antihypertensive response and adverse effects after treatment with zofenopril, 30
      60 mg once daily or amlodipine 5-10 mg od. After receiving the lower starting
      dose, up-titration was optional at 4 weeks to the higher dose if diastolic
      pressure (DBP) was 90 mmHg or more or if a decrease from base line of < 10 mmHg
      was present. After 4 weeks and appropriate up-titration of dose in non-responder
      patients, there were significant and similar reductions of sitting DBP by -10.0
      and -9.9 mmHg and systolic blood pressure (SBP) by -13.0 and -13.2 mmHg the in
      the zofenopril and amlodipine groups, respectively. After 12 weeks of therapy,
      there were further reductions in blood pressure (BP) by the respective therapies.
      Thus, the higher zofenopril dose lowered SBP/DBP by 15.7/12.0 mmHg and the higher
      amlodipine dose by 17.1/ 12.2 mmHg (ns). Also, at the end of the study, the
      percentage of patients controlled (with sitting DBP < 90 mmHg) was 61.4% in the
      amlodipine and 62.2% in the zofenopril group and the percentage controlled (with
      sitting DBP < 90 mmHg and/or a decrease of at least 10 mmHg) was 76.4 in the
      amlodipine and 70.1 in the zofenopril groups (both ns). We conclude that SBP as
      well as DBP were substantially reduced in mild to moderate hypertensive patients
      over 12 weeks treatment with zofenopril or amlodipine in monotherapy. Thus, given
      the size of the BP reduction, such treatments are likely to produce beneficial
      cardiovascular outcome effects in patients with mild to moderate hypertension.

PMID- 18046976
TI  - Antihypertensive efficacy of zofenopril compared with atenolol in patients with
      mild to moderate hypertension.
AB  - Two first-line antihypertensive therapies for initiating treatment in
      hypertension were compared, the angiotensin-converting enzyme inhibitor (ACEI)
      zofenopril and the beta-blocker atenolol. The study was multi-centre and double
      blind, and included 304 middle-aged to elderly patients with mild to moderate
      hypertension who were randomized to receive either zofenopril 30-60 mg once daily
      (od) or atenolol 50-100 mg od for 4 weeks with the possibility to an up-titration
      in non-responding patients. The higher dose level was then administered until 12
      weeks after randomization. Blood pressures (BPs) were substantially reduced by
      either treatment, but after 4 weeks, the systolic and diastolic BP reductions
      were significantly greater (p < 0.05) with zofenopril (-15.6/-13.5 mmHg) compared
      with atenolol (-13.1/-11.8 mmHg). After 12 weeks and the possibility of dose up
      titration, BP differences between treatments were no longer significant. However,
      control rates (sitting diastolic BP < 90 mmHg) for zofenopril remained
      significantly higher compared with atenolol. The number of subjects with adverse
      drug reactions possibly or probably related to the study medication was 14 (9.1%)
      in the zofenopril group and 30 (20.8%) in the atenolol group (p = 0.008). It is
      concluded that zofenopril as well as atenolol induces substantial reductions of
      diastolic BP in middle-aged to elderly patients with hypertension. However, the
      control rate when initiating antihypertensive therapy with zofenopril is higher
      than that for atenolol.

PMID- 18046977
TI  - [Metabolic risk during antipsychotic treatment in patients with schizophrenia].
AB  - Compared with the general population, persons with schizophrenia are
      characterized with an increased prevalence of obesity, type 2 diabetes mellitus,
      and cardiovascular disease. Weight gain and increased adiposity is associated
      with decreases in insulin sensitivity, leading to an increased risk of
      hyperglycaemia and hyperlipidemia. Antipsychotic drugs can increase adiposity and
      the range of trials suggests that treatment with antipsychotic medications may be
      associated with an increased risk of acute (ketoacidosis), subacute (weight gain,
      glucose intolerance, insulin resistance, dyslipidemia), and chronic (diabetes,
      hypertension, coronary heart disease) metabolic complications. Conclusions
      regarding the relative effects of various antipsychotic agents on different
      components of the metabolic syndrome were reviewed, as well as recommendations
      for monitoring these effects were noted. Selection and management of the
      antipsychotic agent reflects a balance between optimizing therapeutic
      effectiveness, modifying diet and exercise, and avoiding excessive weight gain,
      dyslipidemia, and insulin resistance.

PMID- 18046978
TI  - [Genetic polymorphism of COMT in mental disorders].
AB  - Many neurobiochemical studies show abnormalities within dopaminergic
      neuropathways, particularly altered dopamine transmission in etiopathogenesis of
      mental disorders. Evaluation of genes associated with the dopaminergic system
      include five well known subtypes of dopaminergic receptors, dopamine transporter
      and enzymes associated with the synthesis and degradation of dopamine, such as
      tyrosine hydroxylase, dopa decarboxylase, monoamine oxidase (MAO) and catechol O
      methyltransferase (COMT). None of these genes is 'a' pathognomonic factor of
      schizophrenia onset. In each sequence of the following genes 'a' functional
      polymorphism can occur. The polymorphisms of genes MAO-A and COMT have been
      described in relation to various expression or altered activity of these enzymes,
      their influence on cognitive functions, affective and anxiety disorders, learning
      disabilities, aggressive behaviour, eating disorders or gender differences.

PMID- 18046979
TI  - [Genetic polymorphism of a MAO in mental disorders].
AB  - Amin oxydase (monoaminoxydase, MAO) is an enzyme which catalyses chemical
      reactions of biogenic amines. It plays a crucial role in pathogenesis of mental
      disorders associated with the dysfunction of the central monoaminergic systems
      (schizophrenia, affective disorders, some forms of alcohol dependence, and
      personality disorders). MAO has got two isoforms such as MAO-A and MAO-B. The
      genes coding of MAO are localised at the short arm of chromosome Xp11. In each
      sequence of genes there is a probability of functional polymorphism occurrence
      which leads to a variable expression or a change of MAO activity and it exerts an
      impact on the onset of some mental disorders, such as: schizophrenia, affective
      disorders, some forms of alcohol dependence, and personality and behavioural
      disorders. Dynamic development of psychiatric genetics may have crucial impact on
      considerable progress in understanding molecular background of mental disorders.

PMID- 18046980
TI  - [Acute dyskinetic syndrome during chloropromazine treatment of a female patient
      with CYP2D6 poor metabolism phenotype].
AB  - The authors describe the case of a female patient with the diagnosis of
      schizophrenia and the CYP2D6 poor metaboliser phenotype (PM phenotype), who
      experienced severe extrapyramidal side effects, including acute dystonia, while
      being treated with chloropromazine at 100 mg per day (in the third day of
      therapy). The CYP2D6 phenotype was determined using the sparteine test before and
      after 3 days of treatment. Metabolic ratio increased 12 times during treatment,
      from initial 30 to 355. The authors conclude that CYP2D6 poor phenotype leading
      to slow chloropromazine metabolism, which was further inhibited by
      chloropromazine during treatment (as chlorpromazine is a strong CYP2D6 enzyme
      inhibitor) had significant importance on the occurrence of acute extrapyramidal
      side effects. Most likely the antidopaminergic influence of the drug on the CNS
      was much more marked due to an inhibition of chlorpromazine metabolism leading
      probably to an increase of the chlorpromazine blood level.

PMID- 18046981
TI  - [Olfactory dysfunctions in patients with schizophrenia].
AB  - Olfactory dysfunctions in patients with schizophrenia are becoming the aim of an
      increased number of studies. Smell identification deficits are well known but
      also other olfactory processes are examined, eg. sensitivity, discrimination,
      familiarity and edibility. Smell identification deficits are present in patients
      with schizophrenia and also in their non-psychotic siblings. Moreover, this
      dysfunction was reported in a group of children and adolescents with psychosis.
      Patients have also neuroanatomical abnormalites in brains structures linked with
      olfaction, e.g. olfactory bulb. Probably, there is no relationship between
      pathology of olfactory mucosa and olfactory dysfunction. However, correlation
      between smoking, neuroleptic treatment and olfactory deficits was not found, but
      it is unclear what is the role of long-term pharmacotherapy. There is a
      relationship between negative symptoms, IQ and olfactory processing. Smell
      identification deficits are not specific for schizophrenia. This disorder is well
      described in Alzheimer's disease. It is possible that olfactory deficits in
      schizophrenia are induced by pathology in cortical or subcortical regions which
      cannot be detected in neuropsychological tests. Currently it is difficult to use
      olfactory deficits as endophenotypical markers of schizophrenia, and further
      studies are necessary.

PMID- 18046982
TI  - [Correlations between features of social network and outcomes in those suffering
      from schizophrenia seven years from the first hospitalisation].
AB  - AIM: A research had been conducted upon the correlations between selected
      parameters of social networks of 64 patients ill with schizophrenia who were
      diagnosed according to DSM-III, and the aims of treatment such as: motivation to
      receive treatment, insight, compliance in taking medication, satisfaction with
      treatment, and treatment outcomes in the area of clinical and social functioning
      as well as family functioning seven years after the first admission. METHOD: The
      indices of social networks were studied with Bizon's questionnaire. It serves
      storing of data on persons who have supportive functions as well as allows to
      work out characteristic properties of the support system such as: range of the
      network, size of the extra-familial network, level and localisation of the
      support, network and support system age. RESULTS: A compound system of social
      support and large social network, with a high level of support, correlate in a
      beneficial way with higher subjective satisfaction with treatment. Whereas a
      large extra-familial network with high level of support, correlates with better
      insight into illness. The larger the social network was (its range to be
      precise), including extra-familial network and the high level of incoming
      support, the fewer positive and negative symptoms the patients had and much more
      remissions appeared then. The larger network's range correlates with smaller
      number of relapses and global time of being hospitalised. People with a larger
      network, with high level of support located in family and outside the family,
      have been rarely hospitalised. The connection between network's parameters and
      number of daily hospitalisations had been rated. CONCLUSION: People with a larger
      network, including extra-familial network, with high level of social support
      function better in the society didn't become regressive in their professional
      lives and they have smaller burden in their family life. The high level of social
      support correlates with better family function. In families of people ill with
      schizophrenia having larger extra-familial network with a high level of support
      there is less deterioration and disintegration, criticism and rejection.

PMID- 18046983
TI  - [Social network and quality of life of people suffering from schizophrenia in
      seven years from first hospitalisation].
AB  - AIM: The aim of the research was the analysis of a "social network" of people
      suffering from schizophrenia in seven years after first admission and analysis of
      relationships between "social networks" of people suffering from schizophrenia
      and treatment outcomes, the "quality of life" in particular. METHOD: Sixty-four
      patients have been diagnosed according to DSM-III seven years after first
      admission. In this group were 34 men (55.7%) and 27 women (44.3%) and the average
      age was 32 years. Lechman's Life Quality Questionnaire and Bizon's Questionnaire
      of Social Support were used in the study. RESULTS: In the Cracovian longitudinal
      study, persons with a larger network and with a high level of social support
      display better general subjective satisfaction from quality of life. These
      results are confirmed in the research of Lehman and his co-workers, Corrigan and
      Buican. The lack of connection between social network parameters and actual
      health condition as an objective indicator of the quality of life is incompatible
      with the results of some investigators, who claim, that as time flies, the
      impoverishment of the support system is especially threatening to health and
      mental disorders can appear. CONCLUSION: Research upon relationships between
      "social network" and quality of life of persons suffering from schizophrenia
      haven't been widely described in professional literature so far, moreover, the
      obtained results are ambiguous and still raise many doubts.

PMID- 18046984
TI  - [Correlation between cognitive defects and the course of schizophrenia. Initial
      study of a rehabilitation programme participants].
AB  - AIM: Cognitive deficits are the "primary" dysfunction in schizophrenia. They make
      possible a reliable prediction of the broadly understood adjustment of the
      psychiatric patients. The purpose of this paper is to evaluate the relation
      between the results of rehabilitation and the cognitive deficits among the
      patients diagnosed with schizophrenia. METHOD: The assessment of the cognitive
      deficits presented in this paper was conducted using the WCST, the Trial Making
      Test and a verbal fluency tests. These tests evaluated mainly executive
      functioning and working memory. Four indicators of the course of schizophrenia
      were taken into consideration: the severity of symptoms assessed by PANNS, the
      range of social interactions, professional functioning (readiness to be employed)
      and the Quality of Life self-evaluation questionnaire by Olivier. Altogether 64
      patients diagnosed with schizophrenia (in accordance with the DSM-IV and ICD-10)
      who participated in a rehabilitation programme were assessed. RESULTS: The study
      showed correlation between poorer verbal fluency and severity of negative
      symptoms, worse professional functioning, limited range of social interactions
      and lesser satisfaction with work, privacy level and the time spent outside home
      estimated by the QLQ. The poorer results of the TMT correlate with the severity
      of negative symptoms and the level of general psychopathology as well as with
      worse professional functioning. The number of correct answers in the WCST is
      correlated with the level of professional functioning. Persons with higher
      education made less perseverative errors. Persons who managed to finish the first
      category of the test faster are characterised by a broader social interactions
      network. CONCLUSIONS: It was demonstrated that within the studied group of people
      with a long-term course of schizophrenia cognitive deficits correlate with the
      considered indicators of the results of rehabilitation process.

PMID- 18046985
TI  - [Schizophrenic patient's constant refusal of psychotropic medication--case report
      and psychodynamic remarks].
AB  - AIM: The aim of the study was the description of defence mechanisms, phantasies
      and object relations in a non-compliant patient with schizophrenia, who many
      times had refused using antipsychotic drugs in spite of symptom improvement.
      METHOD: Psychodynamic analysis of the case. CONCLUSIONS: Mental functioning of
      the patient based on a narcissistic type of relation, massive primitive defence
      mechanisms, especially splitting, 'no entry defence' and omnipotent denial. The
      authors described the influence of these factors on the efficacy of psychotropic
      medication and compliance of patient.

PMID- 18046986
TI  - [Mental disorders in a female patient with childhood sexual abuse--schizophrenia
      or complex PTSD].
AB  - The paper presents the definition, synonyms of child sexual abuse and a short
      overview of the current knowledge about long-term effects of that kind of trauma.
      The case of a female patient with diagnosed schizophrenia and a history of being
      sexually abused in childhood who was hospitalised at The Department of Psychiatry
      in Lublin is described. Sexual abuse of the child is prolonged, repeated trauma,
      thus another probable diagnosis--Complex PTSD is discussed. The diagnosis of PTSD
      includes the symptoms that result when a person experiences a short-lived trauma.
      However, chronic trauma like child sexual abuse continue for months or years at a
      time and a new diagnosis called Complex PTSD describes the symptoms of long-term
      trauma.

PMID- 18046987
TI  - [Delusional parasitosis: case report].
AB  - A case of a 75-year-old woman suffering from delusional parasitosis is described.
      The patient was referred to the consultant psychiatrist by a dermatologist with
      the diagnosis of psychosis. In course of the psychiatric treatment the patient
      revealed the delusional parasitosis and received antipsychotic treatment
      resulting in full remission. Delusional parasitosis (Ekbom syndrome) is a
      condition where a person has the unshakeable mistaken belief of being infested
      with parasites. Patients give detailed descriptions of the activity and offending
      parasites: crawling, biting, burrowing. According to the contemporary ICD-10
      diagnostic criteria, the delusional parasitosis is a disorder which belongs to
      organic hallucinosis that are usually attached to lonely, old women. In such
      cases, a therapeutic process using antipsychotic treatment is necessary. A
      liaison between dermatologist and psychiatrist is advocated.

PMID- 18046988
TI  - [Basic and clinical analysis of immune cell therapy against advanced renal cell
      carcinoma].

PMID- 18046989
TI  - Possible roles of transcription factors of pseudorabies virus in
      neuropathogenicity.
AB  - Pseudorabies virus (PRV) is also known by its taxonomic name, suid herpesvirus 1,
      or by its original name, Aujeszky's disease virus. PRV is a swine herpesvirus of
      the Alphaherpesvirinae subfamily to which varicella-zoster virus (VZV) and herpes
      simplex virus type 1 (HSV-1) and type 2 (HSV-2) belong. PRV is a pathogen of
      swine resulting in devastating disease and economic losses worldwide. It causes
      severe neurological disorders in infected piglets and latent infection in
      surviving pigs. PRV also causes acute and often fatal infection in other domestic
      and wild animals. PRV has been of interest to virologists and neurobiologists.
      This herpesvirus has served as a useful model organism for the study of
      herpesvirus biology. The virus has also been used as a "live" tracer of neuronal
      pathways, making use of its remarkable propensity to infect synaptically
      connected neurons. Transcription factors of alphaherpesviruses not only control
      the expression of their own viral genes, but also influence the gene expression
      of other viruses and mammalian cells. This review focuses on recent reports
      regarding the use of transgenic mice to study the contributions of PRV
      transcription factors to the neuropathogenicity and the functions of their
      transcriptional regulatory elements.

PMID- 18046990
TI  - [Frequency of gastroesophageal reflux disease (GERD) as a complication in
      patients with chronic liver diseases: estimation of frequency scale for the
      system of GERD].
AB  - Recently, a questionnaire, Frequency Scale for the System of GERD (FSSG), has
      been estimated to be clinically useful for the initial diagnosis of
      gastroesophageal reflux disease (GERD). We investigated the frequency of GERD as
      a complication in patients with chronic liver diseases by using the
      questionnaire, FSSG. As a result, it may be considered that, as a complication of
      chronic liver disease, GERD exists in about 20% of patients and mainly belongs to
      a dyskinetic type.

PMID- 18046991
TI  - Preparation of a quality of life (QOL) questionnaire for patients with type II
      diabetes and prospects for its clinical application.
AB  - Modification of the lifestyle centering on dietary therapy has been proven to be
      effective for the treatment of diabetes mellitus, which is increasing
      progressively. However, lifetime treatment for diabetes inevitably puts economic
      as well as physical and mental burdens on the patients, and many patients drop
      out by discontinuing or neglecting treatment, promoting exacerbation of the
      condition. In this study, an original "Quality of life (QOL) questionnaire for
      patients with type II diabetes" using a visual analogue scale was tentatively
      prepared. To evaluate the reliability and validity of this questionnaire, 126
      patients (64 males and 62 females) being treated as outpatients or inpatients at
      8 university or public hospitals in Fukuoka Prefecture were selected at random,
      and valid answers from 73 patients were analyzed. From the 46 questions, those in
      which no significant correlation was observed or which were not answered by many
      patients were excluded. Since the value of sampling adequacy was 0.673 according
      to the Kaiser-Meyer-Olkin (KMO) measure, the sampling adequacy is considered to
      have been average. When factor analysis by varimax rotation was performed using
      the Statistical Package for Social Science, 4 factors consisting of 18 question
      items were extracted. Eventually, these 4 factors of 18 questions were adopted
      for the QOL questionnaire for patients with type II diabetes. The alpha values of
      the 4 factors were high at 0.867, 0.795, 0.706, and 0.756. These results
      confirmed the internal consistency of the questionnaire and sufficient
      reliability of this analytical method.

PMID- 18046992
TI  - Chronic instability of the anterior syndesmosis of the ankle.

PMID- 18046993
TI  - Pathobiology of oral mucositis: novel insights and opportunities.
AB  - Oral mucositis is a common and debilitatingly painful side effect of many forms
      of chemotherapy and radiation therapy. The erythematous, atrophic, and ulcerative
      lesions that develop are a consequence of epithelial damage and death mediated
      through a complex series of molecular and cellular events. The consequences of
      mucositis are far-reaching and include chemotherapy dose reductions, breaks in
      radiation treatment, cessation of cancer therapy, reliance on parenteral
      nutrition, administration of narcotics, hospitalization, and morbidity. In this
      review, the underlying molecular and cellular pathobiology of oral mucositis is
      characterized in five phases: initiation, the primary damage response, signaling
      and amplification, ulceration, and healing. The roles of reactive oxygen species,
      transduction and transcription pathways, signaling and functional mediators, and
      bacteria on the development and resolution of mucositis are described as a
      dynamic process in which epithelial stem cells are the targets. Insights into the
      mechanisms of oral mucositis are generating new approaches for effective,
      targeted treatment.

PMID- 18046994
TI  - Clinical and economic consequences of mucositis induced by chemotherapy and/or
      radiation therapy.
AB  - Mucositis is a common complication of cancer therapy and can be a debilitating
      and dose-limiting toxicity. Nearly all patients with head and neck cancer treated
      with radiotherapy develop some degree of mucositis, as do the majority of
      patients undergoing high-dose chemotherapy in conjunction with hematopoietic stem
      cell transplantation. Mucositis can have significant clinical and economic
      consequences. It is associated with severe pain that requires opioid analgesics
      and often results in the loss of critical functions such as speech and
      swallowing. Swallowing difficulties can lead to dehydration, weight loss, and the
      need for nutritional support. Furthermore, patients with mucositis are at
      increased risk of infection. Unscheduled dose reductions or treatment breaks due
      to severe mucositis may potentially compromise the efficacy of therapy and result
      in diminished quality of life. Treatment costs for patients with mucositis are
      substantially higher due to increased rates of hospitalization, opioid use, and a
      greater need for fluids and nutritional support. Costs generally increase as a
      function of mucositis severity. Effective treatments to prevent or reduce the
      incidence and severity of mucositis are needed to decrease function loss,
      minimize symptom burden, and lower treatment costs.

PMID- 18046995
TI  - Consequences of mucositis-induced treatment breaks and dose reductions on head
      and neck cancer treatment outcomes.
AB  - Patients with head and neck cancer (HNC) receiving radiation therapy (RT) alone
      or with concurrent chemotherapy (CRT) often develop mucositis that may lead to
      unplanned treatment interruptions and/or chemotherapy dose reductions. Some RT
      schedules have included planned treatment breaks to allow normal tissues to
      recover from these toxicities. These decreases in treatment intensity, however,
      may reduce rates of locoregional tumor control and survival. Any treatment gaps
      allow for tumor repopulation, which may also promote regrowth of chemotherapy
      resistant populations. Therefore, any potential benefits of high-intensity
      therapy may be lost due to interruptions in RT or reduced chemotherapy dose
      intensity, unless the treatment intensity is sufficient to offset interval tumor
      repopulation. Most patients undergoing RT alone and virtually all undergoing CRT-
      particularly those with HNC--will develop mucositis, which doubles the risk of
      reduction in treatment intensity and can increase the rate of hospitalization and
      the use of feeding tubes or total parenteral nutrition. Many of these patients
      with severe mucositis will require a break in treatment or change in
      administration schedule to alleviate symptoms. Effective prophylaxis or treatment
      could reduce the probability of treatment breaks and dose reductions and thus
      improve outcomes.

PMID- 18046996
TI  - Novel agents for the treatment of mucositis.
AB  - Each year, approximately 400,000 people in the United States develop cancer
      treatment-induced oral or esophageal mucositis. Ulceration and inflammation in
      the alimentary tract can be so severe that they compromise treatment and survival
      due to life-threatening complications. These complications may necessitate
      treatment interruption, dose reduction, or cessation of treatment altogether.
      Pain and difficulty eating or swallowing commonly occur and contribute to long
      term morbidity. Until recently, supportive care alone was the mainstay of
      treatment for mucositis. Palliative interventions were based on the concept that
      injury occurred simply at the epithelial level. Although a wide variety of
      palliative treatments were offered to patients, none proved effective at
      prevention, and few agents significantly reduced the duration or severity of
      mucositis. Within the past decade, however, research on the pathogenesis of
      mucositis has revealed a complex sequence of biological events, each of which has
      the potential to serve as a therapeutic target. Initial results with selected
      agents are encouraging, and active research is under way to identify additional
      new drug targets and candidate drugs, which are reviewed here.

PMID- 18046997
TI  - Interpretation of aberrometry measurements in cataract surgery.
AB  - PURPOSE: To discuss the use of wavefront measurements generated from the NIDEK
      OPD-Scan II and OPD-Station for cataract surgery. METHODS: Case examples are
      presented along with information and relevant clinical data obtained from the OPD
      Scan II aberrometer and OPD-Station software. All eyes underwent corneal
      topography, wavefront aberrometry, autorefraction, keratometry, and pupillometry
      measurements pre- and postoperatively using the OPD-Scan II. Optical and visual
      quality simulations, including modulation transfer functions, and visual quality
      attributable to corneal and internal aberrations, were performed using OPD
      Station software. RESULTS: Twelve case examples from cataract surgery, including
      aspheric intraocular lens (IOL) implantation, diffractive IOLs, and toric IOL
      implantation, are presented. CONCLUSIONS: The wavefront analysis in cataract
      surgery was shown to be a fundamental tool in evaluating visual quality after IOL
      implantation. The OPD-Scan II distinguished between corneal and lenticular
      aberrations, allowing for evaluation of actual optical and visual performance
      attributable to the IOL. Our review of case examples also showed that for
      multifocal IOL implantation, a thorough investigation is necessary to correlate
      subjective and objective visual quality and for patient selection.

PMID- 18046998
TI  - Objective assessment of the quality of vision before and after repositioning of a
      dislocated iris-fixated aphakic anterior chamber lens.
AB  - PURPOSE: To document severe visual symptoms due to the dislocation of an iris
      fixated aphakic anterior chamber lens using wavefront aberrometry. METHODS: A
      patient complaining of severe visual blur and distortion due to a decentered
      Artisan iris-fixated anterior chamber lens was evaluated pre- and postoperatively
      after recentration. The patient underwent complete ophthalmic evaluation
      including the measurement of corneal topography and wavefront aberrations using
      the NIDEK OPD-Scan. OPD Station software was used to correlate and simulate the
      patient's symptoms. RESULTS: After the repositioning procedure, the visual
      symptoms resolved, and high magnitudes of tilt (7.536 microm) and high order
      aberrations (5.129 microm) were dramatically reduced by simple lens repositioning
      (4.40-mm pupil). The cylinder magnitude was reduced from 6.25 to 0.75 diopters.
      CONCLUSIONS: These are the first diagnostic images of this kind in a highly
      aberrated eye with iris-fixated anterior chamber lens dislocation. The images
      documented the optical effect and visual consequences of IOL decentration and
      subsequent recentration.

PMID- 18046999
TI  - Long-term effects on corneal keratocytes of mitomycin C during photorefractive
      keratectomy: a randomized contralateral eye confocal microscopy study.
AB  - PURPOSE: To evaluate the long-term side effects of mitomycin C (MMC) assisted
      photorefractive keratectomy (PRK) on corneal keratocytes of highly myopic eyes.
      METHODS: Twenty-eight patients with bilateral myopia from -7.00 to -14.25
      diopters (D) underwent PRK on both eyes, one eye of each patient received topical
      application of 0.02% MMC for 2 minutes immediately after the PRK procedure.
      Corneal keratocyte density was quantified by corneal confocal microscopy at
      baseline and 5 years postoperatively. RESULTS: Photorefractive keratectomy
      reduced keratocyte density in the most anterior stromal layer, without a
      statistically significant difference between MMC and standard treated eyes.
      Posterior stromal layers showed no signs of keratocyte loss with either
      techniques. CONCLUSIONS: Phototherapeutic keratectomy with 0.02% topical MMC has
      no significant side effects on corneal keratocytes compared to standard PRK, as
      documented by in vivo corneal confocal microscopy.

PMID- 18047000
TI  - A prospective, randomized, contralateral eye comparison of epithelial laser in
      situ keratomileusis and photorefractive keratectomy in eyes prone to haze.
AB  - PURPOSE: To compare refractive outcome, subepithelial haze, and pain after
      epithelial laser in situ keratomileusis (epi-LASIK) and photorefractive
      keratectomy (PRK). METHODS: In this prospective, randomized study, 32 eyes of 16
      patients were treated for myopia with epi-LASIK (epi-LASIK group) in one eye and
      PRK in the fellow eye (PRK group). All patients underwent ablation using the
      NIDEK EC-5000 CX II excimer laser platform. Mean patient age was 24.8 years
      (range: 19 to 35 years). Mean preoperative manifest refractive spherical
      equivalent (MRSE) was -2.76 diopters (D) (range: -1.00 to -4.88 D). Refractive
      outcome, subepithelial haze, and pain out to 6 months postoperatively were
      compared between groups. RESULTS: At 6 months postoperatively, the mean MRSE was 
      0.22 +/- 0.27 D (range: 0.25 to -0.88 D) in the epi-LASIK group and -0.23 +/-
      0.29 D (range: 0.50 to -1.125 D) in the PRK group. There was no statistically
      significant difference in the refractive outcomes between groups. By
      postoperative day 4, 18% of the epi-LASIK group and 7% of the PRK group achieved
      the final uncorrected visual acuity (UCVA). On day 1 postoperatively, 14% fewer
      patients in the PRK group experienced pain compared with the epi-LASIK group. On
      postoperative day 2, 36% fewer patients in the epi-LASIK group experienced pain.
      Seventy-one percent of patients in the epi-LASIK group and 36% of patients in the
      PRK group had no haze postoperatively. CONCLUSIONS: Epi-LASIK and PRK produced
      similar refractive outcome. Patients who underwent epi-LASIK experienced faster
      recovery of vision, less haze, and less pain.

PMID- 18047001
TI  - Comparison of laser epithelial keratomileusis with and without mitomycin C for
      wavefront customized surface ablations.
AB  - PURPOSE: To investigate the efficacy of mitomycin C (MMC) in preventing haze
      formation in surface wavefront customized ablations with successful refractive
      treatment (laser epithelial keratomileusis [LASEK]) and to evaluate the safety of
      this technique on corneal stroma and endothelium. METHODS: This study was a
      prospective, double-masked, randomized clinical trial involving 52 eyes (30
      placebo and 22 MMC) of 26 patients. The manifest refractive spherical equivalent
      (MRSE), best spectacle-corrected visual acuity, uncorrected visual acuity,
      corneal pachymetry, topography, aberrometry, endothelial specular microscopy,
      contrast sensitivity, corneal confocal microscopy, and complaints of pain via a
      subjective questionnaire were recorded preoperatively and 90 days
      postoperatively. RESULTS: The mean MRSE at 90 days postoperatively was -0.56
      diopters (D) (-4.95 +/- 1.85 D, range: -8.00 to -1.62 D) for the MMC group and 
      0.49 D (-4.51 +/- 1.81 D, range: -7.75 to -2.25 D) for the placebo group. Higher
      order aberrations were similar between the placebo and MMC groups 90 days
      postoperatively (0.538 +/- 0.228 microm and 0.478 +/- 0.134 microm,
      respectively). Analysis of the endothelial cell count indicated a statistically
      significant decrease in endothelial cell density (P = .017) after LASEK,
      independent of MMC use. CONCLUSIONS: The predictability of the final target
      refraction, induction of high order aberrations, and improvement in contrast
      sensitivity proved that the use of MMC was equally safe when compared to
      procedures that did not use MMC. In addition, the procedure was efficient in the
      prevention of corneal haze.

PMID- 18047002
TI  - Wavefront- versus topography-guided customized ablations with the NIDEK EC-5000
      CX II in surface ablation treatment: refractive and aberrometric outcomes.
AB  - PURPOSE: To compare the long-term refractive outcomes and changes in higher order
      wavefront aberrations in patients undergoing photorefractive keratectomy (PRK)
      with topography-guided (CATz) or wavefront-guided (OPDCAT) ablation algorithm
      using the NIDEK Advanced Vision Excimer Laser System (NAVEX). METHODS: A
      retrospective 12-month follow-up study was conducted of 226 eyes undergoing PRK.
      The NIDEK EC-5000 CX II excimer laser and Final Fit 1.11 treatment planning
      software were used. Sixty-eight eyes underwent OPDCAT ablation and 158 eyes
      underwent CATz ablation. Mean preoperative manifest refractive spherical
      equivalent (MRSE) was -5.73 +/- 2.03 diopters (D) (range: -11.25 to -2.50 D) in
      the OPDCAT group and -3.77 +/- 3.78 D (range: -12.50 to -5.75 D) in the CATz
      group. RESULTS: At 12 months postoperatively, mean MRSE was 0.05 D for the OPDCAT
      group and plano for the CATz group. Stability was similar in both groups as were
      visual outcomes. No eyes lost 2 or more lines of BSCVA at 6 months
      postoperatively or later. Mean ocular wavefront higher order aberrations at 3
      months postoperatively were 0.44 +/- 0.17 microm for the OPDCAT group and 0.55 +/
      0.27 microm for the CATz group. CONCLUSIONS: Refractive outcomes were equivalent
      between eyes that underwent PRK with wavefront-guided ablation and those that
      underwent topography-guided ablation.

PMID- 18047003
TI  - Optimal balance of wavefront aberrations in photorefractive keratectomy.
AB  - PURPOSE: To determine the ratio of defocus (Z4) to spherical aberration (Z12) in
      patients with optimal visual performance 10 years after multifocal aspheric
      photorefractive keratectomy (PRK). METHODS: The optimal ratio of defocus to
      spherical aberration was determined in 16 presbyopic patients (32 eyes) with 10
      year follow-up after aspheric multifocal PRK with good to excellent visual acuity
      postoperatively and the absence of mesopic symptoms such as halos and glare. All
      patients were satisfied with their near and far vision. The NIDEK OPD-Scan was
      used to measure wavefront aberrations postoperatively for a 6-mm pupil diameter
      to the 6th Zernike order. Preoperative manifest refraction spherical equivalent
      (MRSE) was -7.61 +/- 1.04 diopters (D) (range: -6.25 to -10.00 D). RESULTS: At 10
      years postoperatively, mean spherical equivalent refraction was -0.49 +/- 0.96 D.
      All eyes were within 1.00 D of the intended refraction. The ratio of Z4/Z12 for
      patients with optimal outcomes was 3.07 +/- 1.36. CONCLUSIONS: The ratio of
      Z4/Z12 generated in this study determines the optimum balance of defocus to
      spherical aberration required for excellent outcomes in patients undergoing
      multifocal aspheric PRK.

PMID- 18047004
TI  - Active cyclotorsion error correction during LASIK for myopia and myopic
      astigmatism with the NIDEK EC-5000 CX III laser.
AB  - PURPOSE: To investigate the predictability and accuracy of active cyclotorsion
      compensation during LASIK for myopia with astigmatism. METHODS: Fifty-two eyes of
      26 patients were divided into two groups; one group (30 eyes) underwent primary
      LASIK with torsion error correction (TEC [TEC group]) and 22 eyes underwent LASIK
      without TEC (control group). The NIDEK EC-5000 CX III excimer laser was used for
      all treatments. All eyes were targeted for emmetropia. Manifest refraction
      spherical equivalent (MRSE), refractive outcomes, and dispersion and
      predictability of manifest refractive cylinder were compared between the TEC and
      control groups. A P value < .01 was considered statistically significant. All
      outcomes are reported at 3 months postoperatively. RESULTS: Statistically
      significantly lower cylinder dispersion and mean manifest refractive cylinder
      postoperatively were demonstrated in the TEC group (P < .01). Final refractive
      cylinder for the TEC group was -0.21 +/- 0.16 diopters (D) (range: -0.62 to 0.00
      D) and -0.56 +/- 0.34 D (range: -1.25 to 0.00 D) for the control group. No
      statistically significant differences in mean MRSE or safety (defined as a loss
      of 2 or more lines of best spectacle-corrected visual acuity) was noted between
      groups. CONCLUSIONS: LASIK with active cyclotorsion error correction increases
      the accuracy of cylinder correction.

PMID- 18047005
TI  - Confocal microscopy of corneal wound healing after Ho:YAG laser
      thermokeratoplasty.
AB  - PURPOSE: To investigate corneal wound healing using confocal microscopy in
      patients who underwent laser thermokeratoplasty (LTK) for hyperopia between +1.50
      and +3.00 diopters (D). METHODS: In a prospective, nonrandomized study, 78 eyes
      of 42 patients were followed for 1 year using contact and non-contact confocal
      microscopy to evaluate corneal appearance after LTK with the Oko-1 Ho: YAG laser.
      The NIDEK Confoscan 4, 20x non-contact lens and 40x contact lens, was used to
      evaluate the morphology of the corneal layers. The Oko-1 laser was used to reduce
      or eliminate hyperopic refractive error. Patients underwent confocal microscopy
      measurement preoperatively, 1 and 2 weeks and 1, 3, 6, and 12 months after LTK.
      Individual examinations were reviewed and classified by the investigators.
      RESULTS: Preoperatively, spherical hyperopia was +2.11 +/- 0.21 D (range: +1.50
      to +2.75 D). At 3 months postoperatively, the mean manifest refractive spherical
      equivalent (MRSE) was +0.11 +/- 0.02 D and +0.21 +/- 0.02 D at 1 year. Mean
      corneal pachymetry was 631.6 +/- 8.40 microm preoperatively, 637.4 +/- 12.7
      microm at 3 months, and 608.4 +/- 31.7 microm at 1 year. The mean endothelial
      cell density was 2771.4 +/- 28.4 cells/mm2 preoperatively, 2709.4 +/- 122.3
      cells/mm2 at 3 months, and 2693.2 +/- 139.1 cells/mm2 at 1 year. Activated
      keratocytes were present at 3 months postoperatively, which decreased over the
      course of 1 year. CONCLUSIONS: Laser thermokeratoplasty for low to moderate
      hyperopia using the Oko-1 results in formation of intrastromal fibrosis with
      minimal changes in corneal morphology outside the sites of treatment.

PMID- 18047006
TI  - Thin-flap LASIK to increase the range of treatments using the NIDEK EC-5000 CX
      excimer laser.
AB  - PURPOSE: To compare the safety, advantages, and disadvantages of two LASIK groups
      that underwent surgery with a standard-thickness 130-microm microkeratome head
      (standard thickness group) and a 90-microm microkeratome head (thin flap group)
      prior to ablation with the NIDEK EC-5000 CX excimer laser. METHODS: Two hundred
      seventeen patients (420 eyes) with myopia or hyperopia underwent LASIK with
      either a 130-microm microkeratome head (137 eyes of 74 patients) or 90-microm
      microkeratome head (283 eyes of 143 patients). Corneal and stromal bed thickness
      prior to ablation were measured three consecutive times using ultrasound
      pachymetry. Averages of the corneal bed with the flap reflected, the flap
      thickness, and residual stromal bed were calculated for both groups. The
      postoperative appearance of the flaps and stroma in both groups were compared by
      slit-lamp examination. RESULTS: No difference in preoperative corneal thickness
      was found between groups. Eyes that underwent treatment with the 130-microm
      microkeratome head had a mean flap thickness of 163.6 +/- 29.60 microm (range: 71
      to 246 microm). Eyes that underwent treatment with the 90-microm microkeratome
      head had a mean flap thickness of 113.30 +/- 24.26 microm (range: 65 to 182
      microm). No intra- or postoperative complications occurred in either group. Flap
      appearance was similar in both groups. CONCLUSIONS: Both 130-microm and 90-microm
      microkeratome heads have similar predictability. Using a 90-microm microkeratome
      head leaves a thicker stromal bed for ablation.

PMID- 18047007
TI  - Phototherapeutic keratectomy to eliminate postoperative interface sheen in
      hyperopic LASIK.
AB  - PURPOSE: To evaluate the effect of minimal phototherapeutic keratectomy (PTK)
      during primary hyperopic LASIK to eliminate or minimize interface sheen. METHODS:
      Forty-two eyes of 21 consecutive hyperopic patients underwent LASIK using the
      NIDEK EC-5000 CX excimer laser. Mean spherical hyperopia was +3.05 +/- 1.41
      diopters (D) (range: +0.75 to +5.75 D); mean cylinder was -0.88 +/- 0.89 D
      (range: -0.25 to -2.25 D). Mean manifest refraction spherical equivalent was
      +2.70 +/- 1.17 D (range: +0.75 to +5.00 D). Twenty-eight eyes received PTK after
      the refractive ablation whereas 14 eyes did not. The presence or absence of
      interface sheen was noted using slit-lamp microscopy. RESULTS: One (3.5%) eye in
      the group that received PTK ablation had sheen whereas 27 (89%) eyes did not. A
      greater number of cases with sheen occurred in the group that did not receive PTK
      (12 eyes). CONCLUSIONS: Our experience shows that the delivery of minimal PTK
      without a masking agent tends to reduce the incidence of sheen after hyperopic
      LASIK.

PMID- 18047008
TI  - Tangential topography corneal map to diagnose laser treatment decentration.
AB  - PURPOSE: To describe the use of corneal topography to determine the cause of
      decentration and pseudodecentration after laser ablation. METHODS: A total of 148
      eyes referred for treatment of decentration after primary excimer laser surgery
      were evaluated using corneal topography. The criteria and maps used to
      distinguish between decentration and pseudodecentration are described. All eyes
      were analyzed with the tangential algorithm of the CSO corneal topographer and
      the NIDEK OPD-Scan. RESULTS: Eyes were classified into two groups: decentered and
      pseudodecentered. Only 5 (3.4%) eyes were decentered, and 143 eyes were
      classified as pseudodecentered. Analysis of the different causes of
      pseudodecentration included 28 cases due to an irregular ablation, 107 cases due
      to high corneal dioptric gradient, and 8 cases due to central islands.
      Instantaneous corneal topography was the most suitable map to determine
      decentration and pseudodecentration. CONCLUSIONS: Decentration and
      pseudodecentration were due to corneal topographic abnormalities causing sudden
      changes of corneal curvature in the midperiphery. The evaluation of the
      instantaneous curvature maps in this study underscores the importance of these
      peripheral changes by highlighting their impact on the optical performance of the
      central cornea.

PMID- 18047009
TI  - Metabolic activity of the thalamic and telencephalic auditory centers of
      reptiles.

PMID- 18047010
TI  - The human pituitary-thyroid system under chronic exposure to cold.

PMID- 18047011
TI  - To the nature of the effect of glycosidic clathration of pharmacons.

PMID- 18047012
TI  - On the origin of consciousness.

PMID- 18047014
TI  - Human brain responses to sensory stimuli as determined by EEG and fMRT methods
      (pilot studies on the healthy subjects).

PMID- 18047013
TI  - Hormonal response to a synthetic analog of adrenocorticotropic hormone in lynx
      pups (Lynx lynx L.).

PMID- 18047015
TI  - Effect of climatic changes on the zoobenthos of the Barents Sea (on the example
      of several abundant species).

PMID- 18047016
TI  - Specific features of metabolism in male herring gulls (Larus argentatus Pontop.)
      on the Murman coast.

PMID- 18047017
TI  - Phylogenetic relationships between species and intraspecific forms of forest mice
      from the genus Sylvaemus as determined by partial sequencing of the cytochrome b
      gene of mitochondrial DNA.

PMID- 18047018
TI  - Monoclonal and de novo arising tetraploid forms of the genus Cobitis (Cobitidae)
      from different clonal-bisexual complexes.

PMID- 18047019
TI  - Ecological evolution of the phloem of dicotyledonous plants.

PMID- 18047020
TI  - The dependence of interspecific differences in the histoenzymatic parameters of
      skin glands between Norway (Rattus norvegicus) and black (Rattus rattus) rats on
      their social behavior.

PMID- 18047021
TI  - On the taxonomic position of the far eastern red-finned mullet (Mugil so-iuy).

PMID- 18047022
TI  - Correlation of the shoulder girdle asymmetry with the limb skeleton asymmetry in
      Xenopus laevis.

PMID- 18047023
TI  - Dependence of the domination of Anabaenaflos-aquae (Lyngb.) Breb. in the
      phytoplankton community on the initial abundance of akinetes.

PMID- 18047024
TI  - Effect of increased CO2 concentrations on gas exchange and productivity of
      cultivated vegetables contributing to the phototrophic component of biological
      regeneration life-support systems.

PMID- 18047025
TI  - The involvement of phenylalanine ammonia-lyase and salicylic acid in the
      induction of resistance of tomato plants infested with gall nematode Meloidogyne
      incognita.

PMID- 18047026
TI  - Ecological optimum and effect of delayed action of a factor.

PMID- 18047027
TI  - Reproduction success of the herring gull Larus argentatus in Murmansk in 2006.

PMID- 18047028
TI  - Non-predatory mortality indices of cladoceran zooplankton in the pelagial and
      littoral of a shallow meso-eutrophic lake.

PMID- 18047029
TI  - Finding of testate rhizopods (Foraminifera) in a mineral spring north Lake
      Baikal.

PMID- 18047030
TI  - Endemic chromosome races of the common shrew Sorex araneus L. (Insectivora,
      Mammalia) and the possible preservation of refugia in the Late Valdai glaciation
      area.

PMID- 18047031
TI  - Factors of craniometric variability in argali, using an example of Ovis ammon
      polii (Bovidae, Artiodactyla).

PMID- 18047032
TI  - Myelopeptide-5 is a novel endogenous immunoregulator recovering the functional
      activity of T-lymphocytes.

PMID- 18047033
TI  - Proliferation of K19+ human epidermal keratinocytes in vitro.

PMID- 18047034
TI  - Nucleolus organizer activity in lymphocytes of harp seals of different ages.

PMID- 18047035
TI  - Resistance to Erwinia carotovora of plants associated with modified bacteria,
      which have lost their pathogenicity.

PMID- 18047036
TI  - The endocannabinoid system: novel pathway for cardiometabolic Risk-factor
      reduction.
AB  - Although rimonabant has been approved for use in several countries, the Food and
      Drug Administration has expressed concern about the potential for adverse
      neurologic and psychiatric effects, considering the widespread distribution of
      CB1 receptors in the brain. While more research is clearly needed, the clinical
      evidence shows that CB1-receptor blockade with rimonabant improves multiple
      cardiovascular and metabolic variables, including body weight and waist
      circumference, HDL-C, triglycerides, and glucose metabolism. Furthermore, these
      effects, which are probably mediated by both peripheral and central actions in
      the ECS, appear to be greater than the improvements that would be expected from
      weight loss alone. There are multiple ongoing and planned studies with rimonabant
      as well as several other CB-receptor blockers (e.g., taranabant, CP-945,598).
      While diet and exercise are the cornerstones of cardiometabolic risk-factor
      reduction, improved pharmacotherapies are urgently needed. The ECS has provided
      us with new insights and a promising new avenue for the management of obesity and
      its associated cardiometabolic risk factors.

PMID- 18047037
TI  - Clinical aspects of cardiometabolic risk-factor reduction: a case-based approach.

PMID- 18047038
TI  - Combination of differential interference contrast with prism-type total internal
      fluorescence microscope for direct observation of polyamidoamine dendrimer
      nanoparticle as a gene delivery in living human cells.
AB  - A combined system of differential interference contrast (DIC) and total internal
      reflection fluorescence microscope (TIRFM) with a transmitted all-side polished
      dove prism was used for the direct monitoring of polyamidoamine (PAMAM) dendrimer
      nanoparticles as a gene delivery in living human embryonic kidney 293 (HEK 293)
      cells. The PAMAM dendrimer conjugated with fluorescein isothiocyanate (FITC) was
      used to form a fluorescent nanoparticle with the plasmid DNA (complexes) in order
      to directly monitor the entry of the complexes inside living cells. The DIC image
      provided precise information of the living HEK 293 cellular structures. Without
      moving the cell, the TIRFM images of the PAMAM nanoparticle-DNA complexes on the
      all-side polished dove prism provided precise information on the distance between
      the cell membrane and the complexes (< 200 nm) as well as the real-time
      localization of the individual complexes in the cells. The complexes were
      observed in cytosol within 4 h after incubating the cells with the complexes in
      Dulbecco's modified eagle's medium. The localization data of the complexes inside
      the cell obtained by TIRFM were reconfirmed using 3D confocal microscopy images
      of the complexes at the subcellular localization. These results suggest that the
      combined system of DIC and all-side polished dove prism-type TIRFM is a powerful
      tool for the direct real-time monitoring of the internalization and subcellular
      localization of nanoparticles carrying genes through a nonviral approach for gene
      therapy.

PMID- 18047039
TI  - Chitosan-TPP nanoparticle as a release system of antisense oligonucleotide in the
      oral environment.
AB  - Antisense oligonucleotide loaded chitosan nanoparticles were prepared and the
      release of oligonucleotide from chitosan-TPP/oligonucleotide nanoparticles was
      investigated. Morphological property, zeta potential and particle size of the
      prepared chitosan/oligonucleotide nanoparticles were investigated using Field
      Emission-Scanning Electron Microscope (FE-SEM) and particle size analyzer. The
      interaction between chitosan and oligonucleotide was confirmed by using capillary
      zone electrophoresis (CZE), and the released oligonucleotides were determined by
      spectrophotometric method. Oligonucleotides formed the complexes with chitosan
      with a unique morphological property. The release of oligonucleotides from
      nanoparticles was dependent on loading methods and pH conditions.
      Chitosan/oligomer-TPP nanoparticles, which was prepared by adding TPP after the
      formation of chitosan/oligonucleotide complex, showed the lowest release percent
      of oligonucleotides with 41.3% at pH 7.0 among the loading methods. The percent
      release of oligonucleotide from oligonucleotide loaded chitosan nanoparticle at
      pH 10 was higher than the one in acidic condition (pH 5.0). The released
      oligonucleotides from chitosan/oligonucleotide nanoparticles were stable enough
      for 12 h under the 20% saliva solution. Our results suggest that the sustained
      release of oligonucleotide from chitosan nanoparticles may be suitable for the
      local therapeutic application in periodontal diseases.

PMID- 18047040
TI  - Anticancer drug-inorganic nanohybrid and its cellular interaction.
AB  - An anticancer drug, methotrexate (MTX), has been successfully hybridized with
      layered double hydroxide (LDH) through co-precipitation route to produce MTX-LDH
      nanohybrids (MTX-LDH). According to the X-ray diffraction and FT-IR spectroscopy,
      it was confirmed that MTX molecules are stabilized in the interlayer space of
      LDHs by electrostatic interaction, maintaining their functional groups and
      structural integrity. According to the drug release study, the total amount of
      released MTX from the LDH lattice was determined to be larger under a simulated
      intracellular lysosomal condition (pH = 4.5) than simulated body fluid one (pH =
      7.4). It is, therefore, expected that the MTX molecules in MTX-LDH can be
      effectively released in lysosomes, since the MTX release could be accelerated via
      ion-exchange reaction and dissolution of LDH in an acidic lysosomal condition. We
      also examined the anticancer efficacy of MTX-LDH in human breast adenocarcinoma
      MCF-7 cells. The cellular uptake of MTX was considerably higher in MTX-LDH
      treated cells than in free MTX-treated cells, giving a lower IC50 value for the
      former than the latter. All the results demonstrated that the MTX-LDH nanohybrid
      allows the efficient drug delivery in cells, and thus enhances drug efficacy.

PMID- 18047041
TI  - Evaluation for protein binding affinity of maghemite and magnetite nanoparticles.
AB  - We investigated the protein binding affinity of magnetite (Fe3O4) and maghemite
      (gamma-Fe2O3) nanoparticles with against non-characterized protein from human
      lung cancer A549 cell line on sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE). The binding ability of maghemite was 400 ng/mg.
      According to the SDS-PAGE results, the protein binding affinity of maghemite
      nanoparticles is stronger than magnetite nanoparticles. These data suggest that a
      protein can be detected with maghemite nanoparticles.

PMID- 18047042
TI  - Bactericidal effect of TiO2 on the selected Vibrio parahaemolyticus and
      optimization using response surface methodology.
AB  - In this work, the bactericidal effect of TiO2 on selected typical food pathogenic
      bacteria, Vibrio parahaemolyticus was studied. V parahaemolyticus is an important
      pathogen of humans and aqua-cultured animals. We established the response surface
      methodology (Box-Behnken Design) to investigate the effect of principal
      parameters on the cell sterilization such as TiO2 concentration, UV illumination
      time, temperature, and pH. The sterilization rate reached maximum value at the
      TiO2 concentration of 1.0 mg/ml. During irradiation under the time of 30 min with
      UV light with the 1g-TiO2/l, the sterilization rate was greater than 85%, and 99%
      or more cell lost their viability with 3 hours of irradiation. Sterilization rate
      of the cell increased with decrease in the pH and temperature.

PMID- 18047043
TI  - Characterization of nanoporous silicon layer to reduce the optical losses of
      crystalline silicon solar cells.
AB  - Reduction of optical losses in crystalline silicon solar cells by surface
      modification is one of the most important issues of silicon photovoltaics. Porous
      Si layers on the front surface of textured Si substrates have been investigated
      with the aim of improving the optical losses of the solar cells, because an anti
      reflection coating and a surface passivation can be obtained simultaneously in
      one process. We have demonstrated the feasibility of a very efficient porous Si
      AR layer, prepared by a simple, cost effective, electrochemical etching method.
      Silicon p-type CZ (100) oriented wafers were textured by anisotropic etching in
      sodium carbonate solution. Then, the porous Si layers were formed by
      electrochemical etching in HF solutions. After that, the properties of porous Si
      in terms of morphology, structure and reflectance are summarized. The structure
      of porous Si layers was investigated using SEM. The formation of a nanoporous Si
      layer on the textured silicon wafer result in a reflectance lower than 5% in the
      wavelength region from 500 to 900 nm. Such a surface modification allows
      improving the Si solar cell characteristics. An efficiency of 13.4% is achieved
      on a monocrystalline silicon solar cell using the electrochemical technique.

PMID- 18047044
TI  - Photocurrent-voltage of a dye-sensitized nanocrystalline TiO2 solar cells
      influenced by N719 dye adsorption properties.
AB  - Titanium particles of single-phase anatase nanocrystallites were prepared by the
      hydrolysis of titanium tetraisopropoxide. A dye-sensitized solar cell (DSSC) was
      fabricated by adsorbing cis-bis(isothiocyanato)bis(2,2'-bipyridyl-4,4'
      dicarboxylato)-ruthenium(II)bis-tetrabutylammonium dye (N719) onto TiO2 film. The
      samples were characterized by XRD, TEM, FE-SEM, AFM, and Brunauer-Emmett-Teller
      (BET) analysis. The influence of the acetic acid treatment of TiO2 electrode with
      different concentrations on the photovoltaic performance of DSSC was
      investigated. It was found that DSSC had better photoelectric performance when
      the TiO2 electrode was treated by acetic acid of 0.5 M. An equivalent circuit
      analysis using the one-diode model was used to evaluate the influences of
      adsorption quantity and acetic acid treatment on the energy conversion efficiency
      of DSSC. A nonlinear least-square optimization method was used to determine five
      model parameters.

PMID- 18047045
TI  - Hydrochloric acid treatment of TiO2 electrode for quasi-solid-state dye
      sensitized solar cells.
AB  - Quasi-solid-state dye-sensitized solar cell was fabricated by sandwiched polymer
      electrolyte containing liquid electrolytes between the dye-sensitized TiO2
      electrode and a Pt electrode. The influence of hydrochloric acid treatment of
      TiO2 photoelectrode on the photoelectronic performance was investigated. Quasi
      solid-state dye-sensitized solar cell showed better photoelectronic performance
      when the TiO2 electrode was treated with hydrochloric acid than that without
      treatment. The short-circuit current density (J(sc)), the open-circuit voltage
      (V(oc)), and a conversion efficiency obtained for an incident light intensity of
      100 mW m(-2) were 6.49 mA cm(-2), 0.76 V and 4.1%, respectively. It was found
      that the hydrochloric acid treatment of TiO2 electrode increased the short
      circuit current density and cell efficiency.

PMID- 18047046
TI  - The evaluation of individual dispersion of single-walled carbon nanotubes using
      absorption and fluorescence spectroscopic techniques.
AB  - We have investigated the degree of dispersion of single-walled carbon nanotubes
      (SWNTs) in solution using laser spectroscopic techniques. SWNTs were suspended in
      aqueous media using a sodium dodecyl sulfate (SDS) surfactant. SWNTs with
      different dispersion states were prepared by controlling the intensity and
      duration of sonication and centrifugation. The absorption and fluorescence
      spectroscopic techniques were employed to characterize the different dispersion
      state of the prepared samples. Nanotube suspensions with better dispersion showed
      higher fluorescence and sharper absorption peaks. The fluorescence data were
      characterized as a function of the nanotube chirality, and absorption peak shifts
      were analyzed depending on the first and second van Hove singularities (vHs) of
      semiconducting nanotubes.

PMID- 18047047
TI  - Effect of catalyst thickness and plasma pretreatment on the growth of carbon
      nanotubes and their field emission properties.
AB  - We demonstrated that the diameter and the density of carbon nanotubes (CNTs)
      which had a close relation to electric-field-screening effect could be easily
      changed by the control of catalytic Ni thickness combined with NH3 plasma
      pretreatment. Since the diameter and the density of CNTs had a tremendous impact
      on the field-emission characteristics, optimized thickness of catalyst and
      application of plasma pretreatment greatly improved the emission efficiency of
      CNTs. In the field emission test using diode-type configuration, well-dispersed
      thinner CNTs exhibited lower turn-on voltage and higher field enhancement factor
      than the densely-packed CNTs. A CNT film grown using a plasma-pretreated 25
      angstroms-thick Ni catalyst showed excellent field emission characteristics with
      a very low turn-on field of 1.1 V/microm @ 10 microA/cm2 and a high emission
      current density of 1.9 mA/cm2 @ 4.0 V/microm, respectively.

PMID- 18047048
TI  - The bulk piezoresistive characteristics of carbon nanotube composites for strain
      sensing of structures.
AB  - The bulk piezoresistivity of carbon nanotube (CNT) in polymer matrix was
      discussed to develop a strain sensor for engineering applications. The polymer
      improves interfacial bonding between the nanotubes and the CNT composite and that
      enhances the strain transfer, repeatability, and linearity of the sensor. The
      largest contribution of piezoresistivity of the sensor may come from slippage of
      overlaying or bundled nanotubes in the matrix, from a macroscopic point of view.
      Nano interfaces of CNTs in a matrix polymer also contribute to the linear strain
      response compared to other micro size carbon filler. The strain sensor had a low
      bandwidth and adequate strain sensitivity. The nanocomposite strain sensor is
      particularly useful for detecting large strains which can monitor strain and
      stress on a structure with simple electric circuit for strain monitoring of
      structures.

PMID- 18047049
TI  - Novel nanocomposite actuator based on sulfonated poly(styrene-b-ethylene-co
      butylene-b-styrene) polymer.
AB  - Ionic polymer metal composite (IPMC) actuators were developed with multi-walled
      carbon nanotubes (MWNT) and sulfonated poly(styrene-b-ethylene-co-butylene-b
      styrene) (SSEBS) ionic polymers. MWNT with the diameter of 10 approximately 15 nm
      and length of 10 approximately 20 microm was used to enhance the mechanical and
      electrical performances of IPMC actuators. Ultrasonic treatment and high speed
      mixing were employed to disperse MWNTs homogeneously in SSEBS solution. The
      electroless plating method was used to make electrodes on the both side of the
      composite membrane. Scanning electron microscope (SEM) and transmission electron
      microscope (TEM) images were taken to characterize the surface and micro
      structures of the composite actuators. In this study, novel nano-composite
      actuators were fabricated with different weight ratio of the MWNT 0.5%, 1.5% and
      the bending actuation performance and electrical power consumptions were
      investigated.

PMID- 18047050
TI  - Production of nanosized carbon black from hydrocarbon by a thermal plasma.
AB  - Thermal plasma conditions (optimal heat and radical sources for the thermal
      decomposition) can be used to accelerate thermodynamically favorable chemical
      reactions or provide the energy required for endothermic reforming processes.
      Direct thermal decomposition of hydrocarbon (methane, acetylene, and propane) was
      carried out using a thermal plasma system which is an environmentally favorable
      process. In case of thermal decomposition, high purity of the hydrogen and
      solidified nano-sized carbon can be achieved without any contaminant. The main
      product carbon produced by thermal decomposition can be either sequestered or
      used as a raw material and it can be applied for the varieties of industry
      fields. The morphology of the carbon was characterized by SEM and the particle
      size was determined by a particle size analyzer. It was observed that the carbon
      black particles were sphere particles with mainly several tens of nano-sized
      diameters, those are about 10-80 nm. It can be expected to be used as a raw
      material of laser printer toner which requires small sized carbon black
      particles; An average primary particle size of PRINTEX L (Degussa Fillers &
      Pigment) used in a part of printing inks is 23 nm. In case of the XRD pattern of
      the produced carbon black from acetylene is of higher crystalline than the
      commercialized carbon black used for fuel cells. Also carbon species produced
      were characterized by EA and TGA.

PMID- 18047051
TI  - Aqueous-phase synthesis of ultra-stable small CdSe nanoparticles.
AB  - Very stable and small CdSe nanoparticles (NPs) were synthesized from the aqueous
      solutions containing L-cysteine (Cys) at room temperature. The Cys-capped CdSe
      NPs showed a very sharp excitonic peak at 420 nm. Its very small full width at
      half maximum (18 nm) indicates very high quality of the CdSe NPs. Their
      absorption features experienced little change over a month, implying an excellent
      stability of the CdSe NPs. The synthesis conditions were very critical to the
      optical property and stability of the CdSe NPs: only those prepared at specific
      conditions (n(Se-precursor)/n(Cd-precursor) = 0.25-0.5, n(Cys)/n(Cd-precursor) =
      approximately 9, pH = approximately 12) showed very sharp absorption peaks and
      maintained an excellent stability against time. Under these conditions, the peaks
      always appear at nearly the same wavelength, indicating that these NPs are
      selectively stable and grow at a particular size and structure.

PMID- 18047052
TI  - Preparation of highly stable oligo(ethylene glycol) derivatives-functionalized
      gold nanoparticles and their application in LSPR-based detection of PSA/ACT
      complex.
AB  - A sandwich immunoassay for PSA/ACT complex detection based on gold nanoparticle
      aggregation using two probes was developed. The functionalized colloidal gold
      nanoparticles (AuNPs) showed highly stable not only in the presence of high ionic
      strength but also in a wide pH range. The functionalized AuNPs were tagged with
      PSA/ACT complex monoclonal antibody and goat PSA polyclonal antibody and served
      as the probes to induce aggregation of the colloidal particles. As a result,
      PSA/ACT complex was detected at concentrations as low as 1 ng/ml. This is the
      first time that a new aggregation sandwich-immunoassay technique using two gold
      probes has been used, and the results are generally applicable to other LSPR
      based immunoassays.

PMID- 18047053
TI  - Selective atomic layer deposition of metal oxide thin films on patterned self
      assembled monolayers formed by microcontact printing.
AB  - We demonstrate a selective atomic layer deposition of TiO2, ZrO2, and ZnO thin
      films on patterned alkylsiloxane self-assembled monolayers. Microcontact printing
      was done to prepare patterned monolayers of the alkylsiloxane on Si substrates.
      The patterned monolayers define and direct the selective deposition of the metal
      oxide thin films using atomic layer deposition. The selective atomic layer
      deposition is based on the fact that the metal oxide thin films are selectively
      deposited only on the regions exposing the silanol groups of the Si substrates
      because the regions covered with the alkylsiloxane monolayers do not have any
      functional group to react with precursors.

PMID- 18047054
TI  - Unique mechanical properties of nanostructured metals.
AB  - Recently, it becomes possible to fabricate bulk metals having ultrafine grained
      or nanocrystalline structures of which grain size is in nano-meter dimensions.
      One of the promising ways to realize bulk nanostructured metals is severe plastic
      deformation (SPD) above logarithmic equivalent strain of 4. We have developed an
      original SPD process, named Accumulative Roll Bonding (ARB) using rolling
      deformation in principle, and have succeeded in fabricating bulk nanostructured
      sheets of various kinds of metals and alloys. The ARB process and the
      nanostructured metals fabricated by the ARB are introduced in this paper. The
      nanostructured metals sometimes perform quite unique mechanical properties, that
      is rather surprising compared with conventionally coarse grained materials. The
      unique properties seem to be attributed to the characteristic structures of the
      nano-metals full of grain boundaries.

PMID- 18047055
TI  - Influence of catalyst pretreatments on the catalytic oxidation of toluene over
      nanostructured platinum based spent catalyst.
AB  - In this study, we regenerated a nano-structured platinum based spent catalyst by
      applying thermal gas and acid pretreatment and examined the influence of
      treatment on the catalytic oxidation of toluene. The spent catalysts were
      pretreated with air, hydrogen and six different acid aqueous solutions (HCl,
      H2SO4, HNO3, H3PO4, CH3COOH and C2H2O4). The physicochemical properties of the
      parent and its modified catalysts were characterized by XRD, BET, TEM, and ICP.
      The results of light-off curves showed that air and hydrogen treated catalysts
      were more active than the parent catalyst. In addition, the catalytic activities
      of toluene oxidation for acid aqueous treated samples were identical with the
      order of Pt/Al ratio.

PMID- 18047056
TI  - Electrothermal properties of porous ceramic fiber media containing carbon
      materials.
AB  - Electrically regenerable porous ceramic fiber media containing nanoporous carbon
      from 2.5% to 19.2% have been prepared for adsorption/regeneration system. An
      experimental apparatus was built for in situ measurement of the sample weight
      during adsorption and electrothermal desorption of gaseous adsorbates. Adsorption
      and electrothermal desorption behavior of gaseous adsorbates on carbon contained
      porous ceramic fiber media was explained by physical and electrothermal
      properties of these materials measured in this work. In situ thermal desorption
      and adsorption experiments show that a considerable amount of water vapor is
      adsorbed on the carbon contained media exposed to ambient air.

PMID- 18047057
TI  - Low temperature synthesis of colloidal CdSe quantum dots.
AB  - In this study, the CdSe nanocrystals were prepared in phenyl ether and octyl
      amine to investigate the variations of their size, bandgap energy, and
      photoluminescence with growth time and temperature. The sizes of the CdSe
      nanocrystals were measured using High Resolution Transmission Electron Microscopy
      (HRTEM), and found to be nearly monodisperse for relatively low growth
      temperature, 130 degrees C. Their optic properties were characterized by
      photoluminescence measurements, which showed that the colors of the nanocrystals
      could be controlled. The bandgap energies of the nanocrystals were calculated
      theoretically and found to be in accord with quantum confinement theory. This
      synthetic method requires only a cheap solvent and offers good reproducibility at
      a lower price.

PMID- 18047058
TI  - Neutron scintillators of transparent silica xerogel monolith via a sealed
      container system and pi-pi interactions.
AB  - Transparent crack-free lithiated sol-gel scintillating monoliths were developed
      by taking advantage of a sealed container system for a syneresis and the pi-pi
      interactions between sol-gel components and organic fluors to yield a better
      homogeneity and scintillating efficiency. The transparency of the resulting
      materials indicates that the new scintillating material composites are
      mesoscopically dispersed. The silica monolith can be prepared without cladding
      the monolith with an engineering plastic such as a poly(ether ether ketone)
      (PEEK) or a liquid mounting medium. A successful detection of neutron particles
      by using these lithiated scintillating monoliths was demonstrated.

PMID- 18047059
TI  - Silicon subiodide clusters.
AB  - Silicon subiodide clusters (Si(n)I(m), n = 1-20) produced by laser ablation of
      bulk powder silicone tetraiodide have been investigated by time-of-flight mass
      spectroscopy and ab initio calculations. Both experimental results and
      theoretical calculations revealed a tendency to form different structures of the
      clusters depending on n: chain, ring, and cage structures for n < or = 6, 6 < n <
      16, and n > or = 16, respectively. The results showed that iodine, like hydrogen,
      can be used for stable silicon cluster termination.

PMID- 18047060
TI  - Significantly improved adhesion of poly(3,4-ethylenedioxythiophene) nanofilms to
      amino-silane monolayer pre-patterned SiO2 surfaces.
AB  - This study reports a novel patterning method for highly pure poly(3,4
      ethylenedioxythiophene) (PEDOT) nanofilms having a particularly strong adhesion
      to a SiO2 surface. An oxidized silicon wafer substrate was micro-contact printed
      with n-octadecyltrichlorosilane (OTS) monolayer, and subsequently its negative
      pattern was self-assembled with three different amino-functionalized
      alkylsilanes, (3-aminopropyl)trimethoxysilane (APS), N-(2-aminoethyl)-3
      aminopropyltrimethoxy silane (EDAS), and (3-trimethoxysilylpropyl)
      diethylenetriamine (DETS). Then, PEDOT nanofilms were selectively grown on the
      aminosilane pre-patterned areas via the vapor phase polymerization method. To
      evaluate the adhesion and patterning, the PEDOT nanofilms and SAMs were
      investigated with a Scotch tape test, contact angle analyzer, optical and atomic
      force microscopes. The evaluation revealed that the newly developed bottom-up
      process can successfully offer a strongly adhered and selectively patterned PEDOT
      nanofilm on an oxidized Si wafer surface.

PMID- 18047061
TI  - Catalytic performance of nanosized Pt-Au alloy catalyst in oxidation of methanol
      and toluene.
AB  - The alloy formed between a group-VII metal such as platinum and a group-IB metal
      such as gold changes the catalytic behavior compared to the monometallic phase,
      increasing the selectivity toward certain products and also decreasing the
      deactivation rate. Pt-Au alloy nanoparticles coated on alumina support were found
      to be catalytically very active for complete oxidation of methanol and toluene.
      Furthermore, the nanosized Pt-Au particles were added to ZnO/Al2O3 on monolith
      catalyst. Also, effect of various parameters such as concentration of methanol
      and toluene and feed flow rate was investigated. Au particles were sized in 20
      approximately 30 nm and Pt particles were well dispersed. In case of alumina
      supported powder catalyst, complete oxidation of methanol occurred at a
      temperature lower than that of toluene. From oxidation activity of monolithic
      honeycomb with Pt and Au particles, the conversion of methanol was increased with
      increasing the concentration of methanol, but conversion of toluene showed a
      decreasing tendency as the concentration of toluene increased. Also, conversion
      of methanol over honeycomb catalyst was not largely affected by feed flow rate,
      while conversion in toluene oxidation was decreased rapidly as feed flow rate was
      increased. As a result, the Pt-Au/ZnO/Al2O3/M catalyst used is likely to
      efficiently treat a large volume of exhaust gas containing VOCs.

PMID- 18047062
TI  - Positional isomerization of butene-2 over nanoporous MCM-48 catalysts.
AB  - Positional isomerization of butene-2 to butene-1 was investigated over nanoporous
      MCM-48 catalysts. The effects of the method and the amount of aluminum
      incorporation into MCM-48 on the catalyst characteristics were studied, with
      respect to the butene-2 isomerization reaction. Incorporation of aluminum into
      MCM-48 using a post-synthetic grafting method (P) or direct sol-gel method (D)
      increases the total acid amount due to the increase in the Lewis acidity level.
      From the results of butene-2 isomerization, the yield of butene-1 was increased
      although the selectivity of butene-1 was decreased due to an increase of
      byproducts such as i-butene, cracked fraction, and C5+ hydrocarbons. This trend
      is nearly identical over both catalyst preparation methods; the effect of Al
      incorporation method on the butene-1 yield and the selectivity appeared
      negligible. The maximum yield of butene-1 was 27.1 wt% by feeding pure butene-2
      in the reaction condition as follows: a temperature of 450 degrees C, atmospheric
      pressure, and with the WHSV at 70 h(-1).

PMID- 18047063
TI  - Preparation of silver nanoparticles having low melting temperature through a new
      synthetic process without solvent.
AB  - This study presents a new synthetic method of silver nanoparticles using a novel
      polyoxyethylene maleate-based surfactant (PEOM). Unlike conventional process
      using large amount of a solvent to dissolve silver salts, large amount of silver
      salts (AgNO3) can be dissolved and stabilized by our surfactant without solvent.
      Silver salts can be dissociated within PEOM by the formation of charge complex
      between hydrophilic-COOH segments and Ag+NO3-, resulting in formation of self
      assembled microstructures which acting as a nano-reactor and stabilizer. After
      reduction using NaBH4, uniform sized silver nanoparticles were formed in the
      hydrophilic domain of PEOM. Silver contents in the colloids were changed by 0.5
      approximately 3 wt%. Distribution of silver nanoparticle sizes was investigated
      by using TEM and XRD. Melting temperature of silver nanoparticles was measured by
      differential scanning calorimetry, which depends upon the particle size of silver
      nanoparticles. The lowest melting temperature of 112 degrees was measured from
      3.5 nm average-sized silver particles.

PMID- 18047064
TI  - Synthesis and characterization of highly twisted and bulky tetraoctyloxybiphenyl
      containing polyfluorene copolymers: toward efficient blue polymer light emitting
      diodes.
AB  - We have synthesized new blue light emitting random copolymers, poly(9,9'-n
      dioctylfluorene-co-2,2',6,6'-tetraoctyloxybiphenyl-3,3'-diyl)s (PFTOBPs), via
      Ni(0)-mediated coupling reactions. The PL emission peaks of the resulting
      copolymers closely resembled those of the polyfluorene (PF) homopolymer. The EL
      devices fabricated using these copolymers exhibited highly pure blue emission
      with approximate 1931 CIE coordinates of (0.15, 0.15) at 1000 cd/m2. The maximum
      brightnesses ranged from 2000 to 12000 cd/m2 with maximum efficiencies from 0.53
      to 0.97 cd/A. The efficiencies were found to increase as the fraction of TOBP in
      the copolymers was increased, which may result the inhibition of exciton
      quenching that is produced by the introduction of the highly twisted and bulky
      TOBP moieties into the copolymers.

PMID- 18047065
TI  - Effects of oxygen content on bioactivity of titanium oxide films fabricated on
      titanium by electron beam evaporation.
AB  - The titanium oxide films were fabricated on titanium metal by e-beam deposition
      technique in various oxygen partial pressures in order to investigate the effects
      of oxygen content in titanium oxide film on the bioactivity of titanium implant.
      The nano-sized titanium oxide particles were observed on the surface of
      specimens. Raman spectra showed that titanium oxide films deposited by e-beam
      evaporator had oxygen deficient TiO2 structure. The oxygen content in oxide films
      was calculated from the high resolution XPS spectra of Ti 2p. The densities of HA
      particles formed on the sample surfaces after immersion test in SBF became higher
      as the contents of oxygen in titanium oxide films increased. We concluded that
      the degree of hydroxyl group formation in SBF depended on the stoichiometry of
      TiO2, which enhanced the bioactivity of titanium.

PMID- 18047066
TI  - Mixed micelle-template route to mesoporous silica.
AB  - Mesoporous silica materials were prepared through a novel mixed micelle-template
      method which was employed by alkyl polyethylene oxide (C16,E20) and C2-ceramide.
      X-ray diffraction patterns clearly showed the formation of mesoporous silica by
      contribution of mixed micelle-template up to 3/1 weight ratio (C16E20/C2
      ceramide). TEM and N2 adsorption isotherms analyses indicated that the mesoporous
      structure was maintained even after encased C2-ceramides. However, when the
      weight ratio of C16E20/C2-ceramide exceeds 2/2, less ordered and irregular pore
      structure was observed. According to the in-vitro experiment on cancer cells such
      as MCF-7, HOS, and HepG2, the simultaneously encapsulated C2-ceramide shows
      apoptosis. Therefore, the present results could provide a new method for
      mesoporous material as drug delivery system.

PMID- 18047067
TI  - Observation on growth process of gold Y- and phi-shaped nanoparticles in
      solutions.
AB  - The morphological evolution of gold (Au) nanoparticles is demonstrated via TEM
      and UV-vis spectroscopy in a real-time basis. Y-shaped and phi-shaped Au
      nanoparticles were prepared by a seed mediated method at 0 degrees C. The
      evolution of shape ranging from spheres to Y- and phi-shapes was characterized by
      UV-vis spectroscopy. For the spherical particles, the corresponding transverse
      plasmon absorption (540 nm) was observed at the initial growth stage. As further
      growth proceeded, new peaks appeared at ca. 620 nm and ca. 700-1000 nm, which was
      to the characteristic peak of Y-shaped and phi-shaped nanoparticles,
      respectively. In addition, all intermediate steps were observed in the morphology
      change by TEM. At the initial step, spherical particles with 20 nm size were
      generated and the particles were gradually evolved from tiny triangular shape or
      I-shape to Y- and phi-shape. In this study, the growth mechanism of Au
      nanoparticles was investigated by the characterization of optical properties as
      well as morphologies with respect to reaction time.

PMID- 18047068
TI  - Measurement of dispersion stability of surface-modified nanosized carbon black in
      various liquids.
AB  - The dispersion stability of nano-sized carbon black produced by a thermal plasma
      process was investigated using a novel multiple light scattering method. The
      effect of surface modification of carbon black on the dispersion stability was
      monitored in various polar and non-polar liquids including water, methanol,
      styrene, and toluene. The results show that carbon black functionalized with
      carboxylic anion groups has much improved colloidal stability in a polar solvent
      and the degree of dispersion stability is strongly related to the solubility
      parameter value of liquids. In addition, the carbon black with carboxylic anions
      has a long-term stability without any auxiliary dispersion agent such as a
      surfactant due to electrostatic repulsion.

PMID- 18047069
TI  - The functional TiO2-biodegradable plastic composite material produced by HVOF
      spraying process.
AB  - Photocatalytic TiO2 coatings on bio-degradable plastic(polybutylene succinate:
      PBS) were prepared by HVOF spraying using three kinds of agglomerated powders
      (P200: 200 nm, P30: 30 nm, P7: 7 nm). The microstructures of the coatings were
      characterized with SEM and XRD analysis, and the photocatalytic efficiency of the
      coatings was evaluated by photo degradation of gaseous acetaldehyde. For both the
      HVOF sprayed P200 and P30 coatings, high anatase ratio of 100% was achieved,
      regardless of the fuel gas pressure. On the other hand, for the HVOF sprayed P7
      coating, the anatase ratio decreased from 100% to 49.1% with increasing fuel gas
      pressure. This decrease may be attributed to the much higher susceptibility to
      heat of the 7 nm agglomerated powders than the 30 nm and 200 nm agglomerated
      powders. In terms of the photocatalytic efficiency, HVOF sprayed P200 and P30
      coatings seemed to outperform the P7 coatings because of their higher anatase
      ratios. However, the HVOF sprayed P7 coatings did not show photocatalytic
      activity possibly because of the extremely small reaction surface area to the
      photo-catalytic activity and low anatase ratio. Therefore, the present study
      found that functional PBS plastic with photocatalytic performance could be
      produced by spraying of ceramics such as TiO2.

PMID- 18047070
TI  - Electrospinning of aligned biodegradable polymer fibers and composite fibers for
      tissue engineering applications.
AB  - Fibrous membranes of aligned poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV)
      fibers have been made through electrospinning. A high-speed rotating drum was
      used as the fiber collector while the electric field was manipulated by using
      five knife-edged auxiliary electrodes. It was found that a high drum rotating
      speed of 3000 rpm could lead to a nearly perfect alignment of PHBV fibers during
      electrospinning. Multilayered fibrous structures with each layer having a
      different direction of fiber alignment could also be constructed through
      electrospinning. The electrospun PHBV fibers were further modified by
      incorporating carbonated hydroxyapatite (HA) nanospheres (up to 20% of HA) in the
      fibers. The fibrous membranes made of aligned PHBV fibers and made of HA/PHBV
      composite fibers should be very useful for the tissue engineering of different
      human body tissues.

PMID- 18047071
TI  - Material and sensing properties of Pd-deposited WO3 thin films.
AB  - The physicochemical and electrical properties of Pd-deposited WO3 thin films were
      investigated as a function of Pd thickness, annealing temperature, and operating
      temperature for application as a hydrogen gas sensor. WO3 thin films were
      deposited on an insulating material using a thermal evaporator. X-ray
      diffractometry (XRD), field emission scanning electron microscopy (FE-SEM),
      atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS) were
      used to evaluate the crystal structure, microstructure, surface roughness, and
      chemical property of the films, respectively. The deposited films grew into
      polycrystalline WO3 with a rhombohedral structure after annealing at 500 degrees
      C. Adding Pd had no effect on the crystallinity, but suppressed the growth of WO3
      grains. The Pd was scattered as isolated small spherical particles of PdO2 on the
      WO3 thin film after annealing at 500 degrees C, while it agglomerated as
      irregular large particles or diffused into the WO3 after annealing at 600 degrees
      C. PdO2 reduction under H2 and reoxidation under air were dependent on both the
      Pd deposition thickness and annealing conditions. The WO3 thin film with a 2-nm
      thick Pd deposit showed a good response and recovery to H2 gas at a 250 degrees C
      operating temperature.

PMID- 18047072
TI  - Electrical and rheological properties of double percolated poly(methyl
      methacrylate)/multiwalled carbon nanotube nanocomposites.
AB  - Electrical and rheological properties of nanocomposites based on poly(methyl
      methacrylate) (PMMA) and multiwalled carbon nanotube (MWCNT) were studied from
      view points of double percolation by adding crosslinked methyl methacrylate
      butadiene-styrene (MBS) copolymer particles to lower percolation threshold
      concentration of MWCNTs. It was found that the critical concentrations of MWCNTs
      for the percolation in the nanocomposites decrease and then increase with
      increasing the MBS contents of the nanocomposites. It is postulated that the
      addition of MBS at low concentrations results in double percolation of MWCNT and
      the significant decrease of critical concentration for the percolations. However,
      adding MBS particles in large amounts results in limited space for the
      distribution of MWCNTs and less efficient dispersion of the MWCNTs and the
      increase of the critical concentrations of MWCNTs for the percolations.
      Rheological properties and change of T(g)s reflect large interfacial areas in the
      well dispersed nanocomposite and were also interpreted to support the
      speculations for the effects of MBS contents and MWCNT concentrations of
      PMMA/MWCNT nanocomposites.

PMID- 18047074
TI  - Soft-chemical synthesis and electrochemical characterization of multicomponent
      Mn(1-x-y)Co(x)Ni(y)O2 nanostructures.
AB  - Nanostructured Mn(1-x-y)Co(x)Ni(y)O2 metal oxides are synthesized by one-pot
      hydrothermal reaction at low temperature. From powder X-ray diffraction and field
      emission-scanning electron microscopic analyses, it is found that the crystal
      structure and crystal morphology of the present materials are tunable by the
      control of the composition of precursor. 1D nanowires with alpha-MnO2-type
      structure are prepared with low substitution rate of Co and Ni, while the
      increase of substituent contents leads to the formation of delta-MnO2-structured
      3D nanospheres consisting of 2D nanoplates. According to X-ray absorption near
      edge spectroscopy and chemical analyses, mixed valent Co(III)/Co(IV) and divalent
      Ni(II) ions are stabilized in the octahedral Mn sites of alpha-MnO2- and delta
      MnO2-structures. The electrochemical measurements clearly demonstrate that the
      present nanostructured materials show promising electrode performances for
      lithium secondary batteries.

PMID- 18047073
TI  - Preparation and properties of collagen/modified hyaluronic acid hydrogel for
      biomedical application.
AB  - Hydrogels composed of collagen and hyaluronic acid are types of crosslinked water
      swellable polymers and possess vast potential for applications in the medical
      industry. Collagen (Co) is the major structural protein of connective tissues
      such as skin, tendon and cartilage. Hyaluronic acid (HA) is a non-immunogenic,
      non-adhesive glycosaminoglycan that has a high water absorption property and
      plays significant roles in several cellular processes. The purpose of this study
      is to prepare a collagen (Co)-modified hyaluronic acid (MHA) hydrogel and
      investigate its potential utility for biomedical products such as wound dressing
      materials. Collagen (Co, type I) was obtained from pig skin and
      mucopolysaccharide-HA was modified by a poly (ethylene glycol) diglycidyl ether
      (PEGDGE) crosslinker. Thermal stability, swelling behavior, and mechanical
      strength of Co-MHA hydrogel according to different mass ratios of Co and MHA in
      hydrogel networks were investigated. The physical properties of the hydrogel were
      measured by SEM, Differential Scanning Calorimetry (DSC), Thermal Gravity
      Analysis (TGA), and a Universal Testing Machine (UTM). The cell viability of Co
      MHA hydrogel was also evaluated using an in vitro MTT assay.

PMID- 18047075
TI  - The role of Di(2-ethylhexyl)phosphoric acid as a cosurfactant on the morphology
      control of mesoporous silica microspheres.
AB  - Synthesis of mesoporous silica microspheres larger than 10 microm via surfactant
      template approach has rarely been reported. According to the previous studies,
      particle morphologies were highly variable, depending on the synthesis conditions
      and impeller design such as impeller type, size, and agitation speed. A new
      robust surfactant-template synthesis strategy for the stable suspension of large
      silica microspheres was investigated by introducing an additional cosurfactant.
      Di(2-ethylhexyl)phosphoric acid (HDEHP) as a cosurfactant played a key role in
      suspension stabilization without distorting the spherical morphology as well as
      in the formation of uniform pore structures. High quality of mesoporous silica
      microspheres was obtained and compared with the Kosuge's silica under different
      conditions such as stirring rate, acid concentration, the amount of solvent in a
      mother liquor.

PMID- 18047077
TI  - Annealing characteristics of nanostructured Cu-Fe-P alloy processed by
      accumulative roll-bonding.
AB  - Annealing characteristics of a nanostructured copper alloy processed by
      accumulative roll-bonding (ARB) were studied. A nano-grained Cu-Fe-P alloy
      processed by 8 cycles of the ARB was annealed at various temperatures ranging
      from 100 to 400 degrees C for 0.6 ks. The sample still showed an ultrafine
      grained (UFG) structure up to 250 degrees C, however above 300 degrees C it began
      to replace by equiaxed and coarse grains due to an occurrence of the conventional
      static recrystallization. The hardness of the annealed copper decreased largely
      above 300 degrees C. These annealing characteristics of the UFG copper alloy were
      compared to those of a high purity copper.

PMID- 18047076
TI  - Time-dependent X-ray absorption spectroscopic (XAS) study on the transformation
      of zinc basic salt into bis(N-oxopyridine-2-thionato) zinc (II).
AB  - Solid transchelation reaction was established for the synthesis of bis(N
      oxopyridine-2-thionato) zinc (II), commonly known as zinc pyrithione (ZPT), to
      control particle size using zinc basic salt (ZBS) and aqueous sodium pyrithione
      solution. Distinguished from ZPT particles prepared by usual precipitation
      reaction, the obtained ZPT nanoparticles exhibited very narrow size distribution.
      X-ray absorption spectroscopy (XAS) at Zn K-edge was systematically examined to
      elucidate time-dependent local structural evolution during solid transchelation
      reaction. X-ray absorption near edge structure (XANES) analysis clearly revealed
      that local environment around zinc atoms transformed into pentahedron as reaction
      proceeded. Based on quantitative X-ray diffraction and XANES analysis, we made
      structural models. Theoretical XAS spectrum calculated with FEFF code could
      reproduce experimental one, suggesting that XAS analysis could be very powerful
      tool to probe phase transformation. Furthermore, according to extended X-ray
      absorption fine structure (EXAFS) fitting results, Zn-O distance in reaction
      products gradually increased from 1.96 to 2.07 angstroms, suggesting that zinc
      atoms bounded with oxygen ones in ZBS were transchelated with pyrithione ligands.
      This study could be a strong evidence for the usefulness of XAS to study time
      dependent structural transformation of nanocrystalline materials.

PMID- 18047078
TI  - Application of the bimodal meso/macroporous composite synthesized from MCM-41
      sol.
AB  - A route to synthesize porous materials with a bimodal macro/mesoscopic pore
      system has been investigated in this work. Polystyrene with sub-micrometer size
      was used as a template in the synthesis. The resulting mesoporous silica wall
      replicated inversely the morphology of polystyrene template and had highly
      ordered three-dimensional arrays of macro pores. Large and moldable meso/macro
      porous silica monoliths could be obtained in centimeter scale by using
      monodispersed polystyrene beads and MCM-41 sol solutions. These bimodal
      structured porous silicates have been used as supports for asymmetric kinetic
      resolution of racemic epoxides to synthesize optically pure epoxide.

PMID- 18047079
TI  - Encapsulation of Pd complex in ionic liquid on highly ordered mesoporous silica
      MCM-41.
AB  - Palladium acetate was encapsulated onto highly ordered mesoporous silica MCM-41
      with the aid of ionic liquid. The immobilized Pd complex can efficiently catalyze
      Heck coupling reactions of activated and non-activated aryl halides with
      acrylates. The Pd catalyst exhibited remarkably high catalytic activity and
      outstanding stability. Moreover, the immobilized palladium acetate could be
      recycled at least six times without significant loss of activity.

PMID- 18047080
TI  - Ferromagnetic signal in nanosized Ag particles.
AB  - A new technique using an inductively coupled plasma reactor equipped with a
      liquid-nitrogen cooling system was developed to prepare Ag nanoparticles. The
      magnetic signal from these Ag particles with diameters of 4 nm showed,
      surprisingly, a signal with combined ferromagnetic and diamagnetic components, in
      contrast to the signal with only one diamagnetic component from bulk Ag. The same
      technique was used to prepare the Ag/Cu nanoparticles, which are Ag nanoparticles
      coated with a Cu layer. Compared to the Ag nanoparticles, these showed a greatly
      enhanced superparamagnetic signal in addition to the same value of the
      ferromagnetism. The comparison between the Ag and the Ag/Cu nanoparticles
      indicated that the ferromagnetic components are a common feature of Ag
      nanoparticles while the greatly enhanced paramagnetic component of Ag/Cu, which
      dominates over the background diamagnetic component from the Ag core, is from the
      outer Cu shell.

PMID- 18047081
TI  - Silver nanoparticles incorporated electrospun silk fibers.
AB  - We present a simple and mass-producible method of incorporating silver
      nanoparticles on the surface of electrospun silk non-woven membranes for the
      fabrication of antimicrobial wound dressings. Nanofibrous silk membranes with
      fiber diameters of 460 +/- 40 nm were electrospun from an aqueous Bombyx mori
      fibroin solution. The electrospun membranes incorporating silver nanoparticles
      were prepared by dipping the membranes in aqueous silver nitrate (AgNO3) solution
      (0.5 or 1.0 wt%) followed by photoreduction. Field emission scanning and
      transmission electron microscopy showed that silver nanoparticles were generated
      on the electrospun silk fibroin nanofibers as well as inside them. The
      interaction between the silver nanoparticles and amide groups in the silk fibroin
      molecules was characterized using X-ray photoelectron spectroscopy.

PMID- 18047082
TI  - Solvent-induced transition of hollow sphere to giant-tube from amphiphilic rod
      coil-rod triblock copolymers of 2-vinylpyridine and n-hexyl isocyanate.
AB  - The effect of solvent compositions on the micellization behaviors of amphiphilic
      poly(n-hexyl isocyanate)-b-poly(2-vinylpyridine)-b-poly(n-hexyl isocyanate) (PHIC
      b-P2VP-b-PHIC) rod-coil-rod triblock copolymer was studied. In absolute methanol
      the block copolymer formed hollow spherical micelles. These micelles transformed
      into giant-tubes by simply changing the solvent composition. With 20% THF in
      CH3OH hollow spheres got interconnected and formed species that are precursors of
      the giant tubes. When the composition of THF reached 50-70%, long giant tubes are
      formed. Further increasing THF content in the mixed solvent, fragmentation of the
      wall of the tubes was observed. In absolute THF, which is the common solvent for
      both the blocks, the usual phase separation occurred. TEM image of the giant
      tubes stained with iodine showed that the core of the tubes is made from PHIC rod
      block.

PMID- 18047083
TI  - Surface energy heterogeneity and heterogeneous adsorption of benzene on double
      walled carbon nanotubes.
AB  - We examined the adsorption properties of double walled carbon nanotubes (DWCNTs)
      synthesized by using a catalytic chemical decomposition vapor method. To analyze
      the structural and energetical surface characteristics of the DWCNTs, nitrogen
      and benzene adsorption isotherms were measured. The Toth isotherm equation was
      used to correlate the adsorption data and evaluate the thermodynamic properties
      such as Henry's constant and the adsorption second virial coefficient. The
      existence of heterogeneous surface in DWCNTs was confirmed by the analysis of
      pore size distribution, the isosteric heat of adsorption, and the adsorption
      energy distribution determined for nitrogen and benzene.

PMID- 18047084
TI  - Effect of metal powder packing on the conductivity of nanometal ink.
AB  - The power of nanotechnology is realized in its application in numerous areas. One
      such area is undoubtedly the use of metallic nanoparticles as a direct write
      application. An effort in this area has resulted in a conductive ink whose
      conductivity approaches 60-70% that of the bulk copper. Such an ink has been
      developed by reducing silver, gold, and copper nano-sized powders by a wet method
      and followed by a heat treatment at less than 400 degrees C. The conductivity of
      the resulting ink product was found to be very much affected by how various sizes
      of metal powders are packed when particles were dried and packed on various
      substrates. The effect of packing and various kinds of metal powders on the
      eventual conductivity of the final product of the ink has been described and
      discussed in this paper.

PMID- 18047085
TI  - Nanocrystalline particle coatings on alpha-alumina powders by a carbonate
      precipitation and thermal-assisted combustion route.
AB  - We have suggested ultrafine particle coating processes for preparing
      nanocrystalline particle coated alpha-alumina powders by a carbonate
      precipitation and thermal-assisted combustion route, which is environmentally
      friendly. The nanometric ammonium aluminum carbonate hydroxide (AACH) as a
      precursor for coating of alumina was produced from precipitation reaction of
      ammonium aluminum sulfate and ammonium hydrogen carbonate. The synthetic
      crystalline size and morphology were greatly dependent on pH and temperature. By
      adding ammonium aluminum sulfate solution dispersed the alpha-alumina core
      particle in the ammonium hydrogen carbonate aqueous solution, nanometric AACH
      with a size of 5 nm was tightly bonded and uniformly coated on the core powder
      due to formation of surface complexes by the adsorption of carbonates, hydroxyl
      and ammonia groups on the surface of aluminum oxide. The synthetic precursor
      rapidly converted to amorphous- and y-alumina phase without significant change in
      the morphological features through decomposition of surface complexes and thermal
      assisted phase transformation. As a result, the nanocrystalline polymorphic
      particle coated alpha-alumina core powders with highly uniform distribution were
      prepared from the route of carbonate precipitation and thermal-assisted
      combustion.

PMID- 18047086
TI  - Synthesis and electrical property of indium tin oxide nanofibers using
      electrospinning method.
AB  - In this study indium tin oxide (ITO) nanofibers were synthesized using an
      electrospinning method. The morphological properties of the ITO nanofibers were
      considered and their specific resistances were measured to determine their
      applicability as filler for a transparent conducting film. ITO/PVP composite
      nanofibers were successfully obtained by electrospinning using a precursor
      solution containing indium nitrate, tin chloride, and poly(vinlypyrrolidone).
      After the heat treatment of ITO/PVP composite nanofibers at 600 degrees C and
      1000 degrees C, ITO nanofibers with an average diameter of about 168 nm and 165
      nm were synthesized, respectively.

PMID- 18047087
TI  - Synthesis of mesoporous tin oxide and its application as a LNG sensor.
AB  - The nanostructured SnO2 gas sensor with Au electrodes and Pt heater has been
      fabricated as one unit via screen printing process. The gas sensor was tested for
      CH4 sensing behavior at 350 degrees C in the concentration range of 500-10,000
      ppm. Those mesoporous SnO2 sensors exhibited the similar sensoring properties in
      CH4 and CO detection. The fast speed of response and high sensitivity were
      obtained for mesoporous tin oxide sensor as compared to non-porous one.

PMID- 18047088
TI  - Electrical properties of silver paste prepared from nanoparticles and lead-free
      frit.
AB  - Recently, PbO containing glass systems in commercial silver paste have been used
      due to their low glass transition temperature, good thermal and electrical
      properties. However, PbO is a hazardous material to both health and the
      environment. In this study, Pb-free silver paste was prepared by mixing
      commercial silver powder and silver nanoparticles. The commercial powder has an
      average particle size of 1.6 microm. The silver nanoparticles with particles size
      of 20-50 nm were synthesized by a chemical reduction method using surfactant. Pb
      free frit was added into the mixed silver powder as the amounts of 3, 6 and 9
      wt%. Using the obtained paste, thick films were fabricated by a screen printing
      on alumina substrate and the films were fired at temperature from 400 to 550
      degrees C. The films had thickness of 6-11 microm and sheet resistivity of about
      4-11 microomega cm.

PMID- 18047089
TI  - Aggregation behavior of Na-neutralized styrene-ran-methacrylic acid copolymers in
      aqueous solution.
AB  - The aggregation behavior of un-neutralized, partly and fully Na-neutralized
      poly(styrene-ran-methacrylic acid) copolymers in aqueous solution was
      investigated using a SEM technique. It was observed that the un-neutralized
      copolymer formed spherical particles on the Si wafer, and the average size of
      particles was ca. 160 nm. The particle sizes did not change much with acid
      content. Upon the neutralization of the acid groups of the copolymer with NaOH,
      the copolymer became more hydrophilic, leading to the formation of network-like
      feature consisting of much smaller particles (< 50 nm), compared to those of the
      acid copolymers. With increasing ionization, the boundary of the particles
      forming networks faded away, implying the formation of tubular structures.

PMID- 18047090
TI  - Catalytic Si-Si/Si-O dehydrocoupling of 1,1-dihydrotetraphenylsilole to
      optoelectronic polysiloles with colloidal silver nanoparticles.
AB  - The combinative Si-Si/Si-O dehydrocoupling at ambient air atmosphere of 1,1
      dihydrotetraphenylsilole 1 with 2 mol% of AgNO3 and Ag2SO4 in toluene at 90
      degrees C produces optoelectronic polysiloles 2 in high yield. The complexes such
      as Cp2Co, Cp2Ni, Cp2ZrCl2/Red-Al, and AgCl were found to be ineffective for the
      dehydrocoupling of 1. The polysiloles mainly have Si-Si bonds along with the
      small portion of Si-O bonds in the polymer backbone chain. Interestingly, the Si
      O linkage increased with increasing the concentration of catalyst AgNO3, implying
      that while Ag(0) species catalyze the Si-Si dehydrocoupling, Ag(I) species
      catalyze the Si-O dehydrocoupling along with the simultaneous oxidation of NO3
      ion to NO2. The silver complexes transformed to colloidal silver nanoparticles
      during the catalytic reaction. The Si-Si/Si-O dehydrocoupling of 1 with AgNO3
      even at dry nitrogen atmosphere is occurred, supporting that the oxidation of NO3
      ion to NO2 is only the possible oxygen source, but not from the adventitious
      moisture in air. sigma-, beta-, and gamma-Cyclodextrins considerably deteriorated
      the dehydrocoupling of 1 probably due to both the formation of insoluble
      inclusion complexes in toluene and the encapsulation of SiH2 moiety. The
      resulting silole polymer 2 emits green light at 520 nm and is electroluminescent
      at 520 nm.

PMID- 18047091
TI  - Characterization of nanoporous structures of polyphenylene oxide derived carbon
      membranes by means of 129Xe NMR.
AB  - The 129Xe NMR spectroscopy has become a powerful technique of materials
      characterization because the xenon atom has a very large polarizability. It is
      well known that the signal of xenon sorbed in porous media is sensitively
      affected by the surrounding environments such as the chemistry of material
      surface. In this study, the pore properties of nanoporous PPO (polyphenylene
      oxide) derived carbon membranes were characterized by means of the variable
      temperature (VT)-hyperpolarized Xe NMR. The Xe NMR results showed good agreements
      with the adsorption results of CO2 for the PPO derived nanoporous carbon
      membranes. It was clearly shown that the 129Xe NMR could be used as one of the
      promising characterization methods of nanoporous materials with low surface area
      and small pore volume.

PMID- 18047092
TI  - Microbial synthesis of magnetite and Mn-substituted magnetite nanoparticles:
      influence of bacteria and incubation temperature.
AB  - Microbial synthesis of magnetite and metal (Co, Cr, Ni)-substituted magnetites
      has only recently been reported. The objective of this study was to examine the
      influence of Mn ion on the microbial synthesis of magnetite nanoparticles. The
      reductive biotransformation of an akaganeite (beta-FeOOH) or a Mn-substituted (2
      20 mol%) akaganeite (Fe(1-x)Mn(x)OOH) by Shewanella loiha (PV-4, 25 degrees C)
      and Thermoanaerobacter ethanolicus (TOR-39, 60 degrees C) was investigated under
      anaerobic conditions at circumneutral pH (pH = 7-8). Both bacteria formed
      magnetite nanoparticles using akaganeite as a magnetite precursor. By comparison
      of iron minerals formed by PV-4 and TOR-39 using Mn-mixed akaganeite as the
      precursor, it was shown that PV-4 formed siderite (FeCO3), green rust
      [Fe2+Fe3+(OH)16CO3 x 4H2O], and magnetite at 25 degrees C, whereas TOR-39 formed
      mainly nm-sized magnetite at 60 degrees C. The presence of Mn in the magnetite
      formed by TOR-39 was revealed by energy dispersive X-ray analysis (EDX) is
      indicative of Mn substitution into magnetite crystals. EDX analysis of iron
      minerals formed by PV-4 showed that Mn was preferentially concentrated in the
      siderite and green rust. These results demonstrate that coprecipitated/sorbed Mn
      induced microbial formation of siderite and green rust by PV-4 at 25 degrees C,
      but the synthesis of Mn-substituted magnetite nanoparticles proceeded by TOR-39
      at 60 degrees C. These results indicate that the bacteria have the ability to
      synthesize magnetite and Mn-substituted magnetite nano-crystals. Microbially
      facilitated synthesis of magnetite and metal-substituted magnetites at near
      ambient temperatures may expand the possible use of specialized ferromagnetic
      nano-particles.

PMID- 18047093
TI  - Preparation of liposomes containing oleanolic acid via micelle-to-vesicle
      transition.
AB  - Micelle-to-vesicle transition method was used to make liposomes containing
      oleanolic acid. First, the solubilization of potassium salt of oleanolic acid at
      basic condition by micelle formation was confirmed. Using the soluble state of
      oleanolic acid at basic condition, liposomes containing oleanolic acid was
      prepared by adjusting pH. After making homogeneous aqueous mixture of potassium
      salt of oleanolic acid and lecithin in basic condition, the solution was
      neutralized to produce the lecithin-based liposomes that contain oleanolic acid
      inside the lipid bilayers. The optimal loading of oleanolic acid to lecithin
      (about 25 mole%) was found to exist to produce liposomal suspension of small size
      without homogenization step. Electron microscopy and dynamic light scattering
      studies showed that the narrowly distributed, reconstituted oleanolic acid
      containing liposomes were prepared without severe mechanical treatment.

PMID- 18047094
TI  - A new synthesis route to nanocrystalline olivine phosphates and their
      electrochemical properties.
AB  - LiFePO4 nanoparticles were synthesized in various polyol mediums without any
      further heating. The LiFePO4 samples synthesized in polyol mediums exhibited
      average sizes of 20, 20, 50, and 50 nm with orthorhombic-like shapes. The XRD
      patterns were indexed on the basis of an olivine structure (space group : Pnma)
      except for the sample prepared in EG polyol medium. The LiFePO4 samples prepared
      in EG, DEG, TEG, and TrEG polyol mediums show the reversible capacity of 120 mA
      h/g, 144 mA h/g, 159 mA h/g, and 167 mA h/g at current density of 0.1 mA/cm2 with
      no capacity fading and excellent cycle retentions during extended cycles.
      Especially, the samples showed the excellent performances at high rate of 30 C
      and 60 C with high capacity retention. It is a speculation that nanometer size
      materials (approximately 50 nm) and a uniform size-distribution with highly
      crystallined phase may affect the excellent performances at high rate current
      densities.

PMID- 18047095
TI  - A polyol-mediated synthesis of titania-based nanoparticles and their
      electrochemical properties.
AB  - Ti-based nanoparticles were prepared in polyol mediums of EG (ethylene glycol)
      and TEG (triethylene glycol), with heating treatment. Ti-based materials of dried
      power and heated samples showed average sizes of 4, 10, 3, and 8 nm with
      spherical shapes and monodispersed state, respectively. The XRD patterns of TiO2
      and Li4Ti5O12 materials of dried powder and heated samples were indexed to
      anatase phase TiO2 (space group: I4(1)/amd) and the spinel phase (space group:
      Fd3m) except for the dried powder sample of Li4Ti5O12, which was corresponded
      with amorphous-like characteristics from the X-ray diffraction and electron
      diffraction pattern of Field emission-TEM analysis. The TiO2 and Li4Ti5O12
      samples after heat-treated at 500 degrees C exhibited excellent high rate
      capabilities at a current density of 0.4 mA/cm2 during extended cycles due to
      their electrochemically beneficial highly crystalline characteristics, nano-sized
      (approximately 10 nm), and uniform distributions state.

PMID- 18047096
TI  - Catalytic decomposition of 1,2-dichlorobenzene using Pt-loaded nanoporous zeolite
      MFI catalyst.
AB  - Nanoporous zeolite MFI was prepared by using HClO4 as a promoter. A significant
      proportion of the synthesized zeolite MFI nanoparticles exhibited nanoporous
      characteristics. Although the synthesis of the zeolite MFI was completed within 6
      h, the crystallinity of all the zeolite MFI was shown to be high. The synthesis
      time of approximately 6 h used in this study was much shorter than the
      conventional hydrothermal method. The feasibility of the new nanoporous zeolite
      MFI towards the gas phase catalytic oxidation of a model for dioxin, 1,2
      dichlorobenzene, was tested by comparing the catalytic activity of Pt/nanoporous
      zeolite MFI with that of a Pt/gamma-Al2O3 catalyst. The catalytic activity of the
      Pt/nanoporous zeolite MFI was higher than that of the Pt/gamma-Al2O3 catalyst.
      The internal surface area and acidity appears to be a major factor for the
      decomposition of 1,2-dichlorobenzene.

PMID- 18047097
TI  - Dry sol-gel polycondensation of hydrosilanes to organosilicas catalyzed by
      colloidal nickel nanoparticles.
AB  - The dry sol-gel polycondensation at toluene in ambient air atmosphere of p-X
      C6H4SiH3 (X = H, CH3, CH3O, F, Cl) to silica p-X-C6H4SiO15 in high yield,
      catalyzed by colloidal nickel nanoparticles in-situ generated from
      nickelocene(II), nickel(II) acetate, and bis(1,5-cyclooctadiene)nickel(0), is
      described. Similar catalytic activities were observed for the catalysts.
      Similarly, the dry sol-gel polyco-condensation p-X-C6H4SiH3 (X = CH3, CH3O, F,
      Cl):C6H4SiH3 (9:1 mole ratio) at toluene in ambient air atmosphere of was
      performed to yield co-silicas (p-X-C6H4SiO1.5)9(p-X-C6H4SiO1.5)1 in high yield
      using nickelocene. The co-gels with higher molecular weights and TGA residue
      yield were obtained when compared to the homogels. The highest yield, molecular
      weight, polydispersity index, and TGA residue yield were obtained for p-Cl
      C6H4SiH3. Some degree of unreacted Si-H bonds still remained in the gel matrix
      because of steric bulkiness. All the insoluble gels adopt an amorphous structure
      with a smooth surface. A plausible mechanism for the dry sol-gel reaction was
      suggested.

PMID- 18047098
TI  - Effect of the on/off cyclic modulation time ratio of C2H2/H2 flow on the low
      temperature deposition of carbon nanofilaments.
AB  - Low temperature (less than 600 degrees C) deposition of carbon nanofilaments
      (CNFs) could be achieved on the silicon oxide substrate by thermal chemical vapor
      deposition system. We used Fe(CO)5 as the catalyst precursor for CNFs formation.
      For the enhancement of CNFs formation density, the source gas flow was
      intentionally manipulated as the cyclic on/off modulation of C2H2/H2 flow during
      the initial deposition stage. The CNFs formation density on silicon oxide
      substrate could be much enhanced by the cyclic modulation process having the
      higher growing/etching time ratio (180/30 s). Furthermore, the lattice structures
      of CNFs developed into carbon nanotubes at the higher growing/etching time ratio
      (180/30 s) case. The solely hydrogen gas feeding (C2H2 flow off) time during the
      initial deposition stage seems to play an important role for the variation in the
      CNFs formation characteristics by the cyclic modulation process.

PMID- 18047099
TI  - Hysteresis in a carbon nanotube based electroactive polymer microfiber actuator:
      numerical modeling.
AB  - Hysteretic behavior is an important consideration for smart electroactive polymer
      actuators in a wide variety of nano/micro-scale applications. We prepared an
      electroactive polymer actuator in the form of a microfiber, based on single-wall
      carbon nanotubes and polyaniline, and investigated the hysteretic characteristics
      of the actuator under electrical potential switching in a basic electrolyte
      solution. For actuation experiments, we measured the variation of the length of
      the carbon-nanotube-based electroactive polymer actuator, using an Aurora
      Scientific Inc. 300B Series muscle lever arm system, while electrical potentials
      ranging from 0.2 V to 0.65 V were applied. Based on the classical Preisach
      hysteresis model, we presented and validated a numerical model that described the
      hysteretic behavior of the carbon-nanotube-based electroactive polymer actuator.
      Inverse hysteretic behavior was also simulated using the model to demonstrate its
      capability to predict an input from a desired output. This numerical model of
      hysteresis could be an effective approach to micro-scale control of carbon
      nanotube-based electroactive polymer actuators in potential applications.

PMID- 18047100
TI  - Nanosized LiFePO4 cathode materials for lithium ion batteries.
AB  - In this study, we prepared nano-particles of LiFePO4 as cathode material for
      lithium ion batteries by the solid-state reaction. A simple one-step heat
      treatment has been employed with control of heating temperature and heated
      LiFePO4 at 650 degrees C exhibited higher 125 mA h/g of the discharge capacity
      than 600 degrees C, 700 degrees C. To improve conductivity of the inter-particle,
      carbon coating was carried out by raw carbon or pyrene as carbon sources and
      their morphological properties of particles on the carbon coating was compared
      with by FE-SEM, TEM. From the FE-SEM results, the particles of carbon added
      LiFePO4 have much smaller size than LiFePO4 as below 300 nm. When adding pyrene
      (10 wt%), the carbon surrounded non-uniformly with surface of the particles
      compared with adding raw carbon which wrapped uniformly with carbon web and it
      was exhibited 152 mA h/g of the discharge capacity on LiFePO4/C composite cells
      at 10th cycle.

PMID- 18047101
TI  - Nanostructured bulk copper fabricated by accumulative roll bonding.
AB  - In this study, we tried to fabricate the nanostructured bulk copper alloys by a
      severe plastic deformation process. The sheets of copper alloys (OFC, PMC90, and
      DLP) were heavily deformed to an equivalent strain of 6.4 by the accumulative
      roll-bonding (ARB) process. The microstructure and the mechanical property of the
      fabricated specimens were systematically investigated. The microstructure was
      finely subdivided with increasing the equivalent strain by the ARB process. The
      severely deformed copper alloys exhibited the ultrafine lamellar boundary
      structure where the mean lamella spacing was about 200 nm. The strength
      significantly increased with decreasing the lamella spacing in the ARB processed
      copper alloys. Especially, the tensile strength of the DLP alloys ARB processed
      by 8 cycles (the equivalent strain of 6.4) reached to 520 MPa, which was about
      three times higher than that of same materials with conventional grain size of 10
      100 microm. On the other hand, the total elongation greatly dropped only by 1 ARB
      cycle corresponding to an equivalent strain of 0.8, which was around 3%. However,
      the total elongation increased again with increasing the number of the ARB cycle,
      and it reached to 10% after 8 cycles. The recovery of the total elongation could
      be recognized in all studied copper alloys. The obtained stress-strain curves
      showed that the improvement of the total elongation was caused by the increase in
      the post-uniform elongation. It can be concluded that the nanostructured copper
      alloys sheets having high strength without a large loss of ductility could be
      fabricated by the ARB process.

PMID- 18047102
TI  - Properties of polypropylene nanocomposites containing silver nanoparticles.
AB  - Silver/polypropylene (PP) nanocomposites containing silver nanoparticles smaller
      than 10 nm were prepared using a new synthetic method. AgNO3 crystals were
      dissolved into hydrophilic domain of polyoxyethylene maleate-based surfactant
      (PEOM), which gives self-assembly nano-structures. The AgNO3 in the nano-domains
      of PEOM was reduced by NaBH4 to form nanoparticles. The colloidal solutions with
      silver nanoparticles were diluted with ethanol and were mixed with PP pellets.
      Silver nanocomposites were prepared by extrusion compounding process after drying
      the pellets. Contents of silver nanoparticles dispersed within PP resin were
      changed from 100 to 1000 ppm. Formation of silver nanoparticles within PP was
      confirmed by UV-Vis spectroscopy and TEM. Size and distribution of dispersed
      silver nanoparticles were also measured by TEM. Silver/PP nanocomposites films
      showed not only improved thermal stability but also increased mechanical
      properties compared to neat PP film. Tensile properties of PP nanocomposites were
      largely improved compared with neat PP resin, and elongation increased also by
      175% for the nanocomposites containing 1000 ppm silver nanoparticles.

PMID- 18047103
TI  - Surface modification for polystyrene colloidal particles with controlled charge
      densities.
AB  - A significant amount of polystyrene sulfonated acid (PSSA) and poly(styrene-ran
      acrylic acid) (PSAA) random copolymer can be adsorbed by dispersion of PS
      particles via a swelling-quenching process. A THF-water mixed solvent was used in
      the swelling process and a large amount of pure water was used, to give a low
      concentration of THF% in quenching process. Our results showed that functional
      PSSA groups were randomly and tightly adsorbed to the PS particles. When the
      mol.% of charged segments was increased, the progressive adsorption of PSSA
      chains to the PS particles leads to an increase in the electrophoretic mobility
      and zeta-potential of aqueous dispersions. Thus, we were able to obtain well
      distributed surface charge density on the PS particles.

PMID- 18047104
TI  - Use of polymer nanoparticles as functional nano-absorbents for low-molecular
      weight hydrophobic pollutants.
AB  - To use amphiphilic polymer nanoparticles as a new nano-absorbent for improving
      environmental process, urethane acrylate nonionomer (UAN) chain having
      hydrophobic polypropylene oxide-based segment and hydrophilic polyethylene oxide
      based segment at the same backbone was synthesized and dispersed as nanoparticles
      at water phase without using a surfactant or dispersion agent. These UAN
      nanoparticles were converted to crosslinked amphiphilic polymer (CAP)
      nanoparticles through soap-free emulsion polymerization and suspension agent-free
      suspension polymerization process. Emulsion polymerization process exhibited
      higher conversion of polymerization compared to suspension polymerization
      process. CAP nanoparticles showed interfacial activity and solubilize hydrophobic
      pollutants (phenanthrene and toluene) like surfactant micelles. This result
      indicates possible application of CAP nanoparticles as nano-absorbent for
      improving efficiency of soil washing and micellar-enhanced ultrafiltration (MEUF)
      process.

PMID- 18047105
TI  - A hydrogen peroxide biosensor based on peroxidase activity of hemoglobin in
      polymeric film.
AB  - A Hydrogen peroxide (H2O2) biosensor, based on hemoglobin (Hb) and ortho
      phenylenediamine (o-PD) gold electrode, was fabricated. Hb was immobilized onto
      the electrode surface by electrochemical polymerize method with o-PD. The
      designed biosensor showed a well defined redox peak which was attributed to the
      direct electrochemical response of Hb. The immobilized Hb exhibited an excellent
      electrocatalytical response to the reduction of hydrogen peroxide, enabling the
      sensitivity determination of H2O2. Factors and performances such as pH,
      potential, influencing the designed biosensor, were studied carefully. The
      amperometric detection of H2O2 was carried out at -300 mV in phosphate buffer
      solution (PBS) (0.1 M) with pH 6.0. This biosensor showed a fast amperometric
      response (less then 5 s) to H2O2. The levels of the (Relative standard deviation)
      RSDs (< 3.5%) for the entire analyses reflected a highly reproducible sensor
      performance. Using the optimized conditions, the detection limit of the biosensor
      was 1 x 10(-7) M and linear range was from 5 x 10(-6) to 1.25 x 10(-4) M. In
      addition, this sensor showed long-term stability and good sensitivity.

PMID- 18047106
TI  - Autothermal reforming of propane over hydrotalcite-like catalysts containing
      promotor.
AB  - Hydrotalcite-like catalysts were synthesized by co-precipitation and then these
      were promoted by the addition of noble metals, alkaline earth metals and ceria.
      Reaction tests were conducted using a feed of H2O/C/O2 = 3/1/0.37 at a
      temperature range from 300 degrees C to 700 degrees C. Catalysts were
      characterized by XRD, TEM, FESEM, TPR, and BET. Reaction test results confirmed
      an enhancement of the catalytic activity of the promotor-modified catalysts due
      to low carbon deposition. Among the alkaline earth metals tested, those with
      larger atomic number exhibited higher activity at a lower temperature range.

PMID- 18047107
TI  - Autothermal reforming of propane over Ni catalysts supported on a variety of
      perovskites.
AB  - Autothermal reforming of propane for hydrogen over Ni catalysts supported on a
      variety of perovskites was performed in an atmospheric flow reactor. Perovskite
      is known for its higher thermal stability and oxygen storage capacity, but
      catalytic activity of itself is low. A sites of the ABO3 structured perovskites
      were occupied by La while B sites by one of Fe, Co, Ni, and Al by citrate method.
      The composition of the reactant mixture was H2O/C/O2 = 8.96/1.0/1.1. The changes
      in the states of the catalysts after reaction were analyzed by XRD, TPD, and TGA.
      Ni/LaAlO3 catalyst maintained the perovskite structure after reaction. It showed
      higher hydrogen yield and thermal stability compared to those of the catalysts
      with Fe, Co, or Ni in B sites. Catalysts prepared by deposition-precipitation
      (DP) method showed higher activity than those prepared by impregnation method,
      presumably due to the smaller sizes of the NiO crystal particles.

PMID- 18047108
TI  - Cellular toxicity of inorganic hydroxide nanoparticles.
AB  - Layered double hydroxides (LDHs), anionic clays, have attracted increasing
      interest as nanovehicles for delivering genes, drugs, and bio-active molecules
      into cells. However, no attempts have been made to evaluate the potential
      undesirable effects of LDH nanoparticles. The cytotoxicity of LDHs with different
      chemical compositions (ZnAl- and MgAl-LDH) was systematically evaluated in
      various cell types, such as human normal cells, carcinoma cells, and red blood
      cells, by measuring cell viability, cell proliferation, membrane damage, and
      hemolytic effect. No significant cytotoxic effects could be seen in both cases,
      but ZnAl-LDH was determined to be slightly more toxic than MgAl-LDH in terms of
      membrane damage and hemolysis induction. It is, therefore, expected that LDHs
      could be promising candidates for novel inorganic drug delivery carriers.

PMID- 18047109
TI  - Decrease in work function of boron ion-implanted ZnO thin films.
AB  - We have fabricated boron ion-implanted ZnO thin films by ion implantation into
      sputtered ZnO thin films on a glass substrate. An investigation of the effects of
      ion doses and activation time on the electrical and optical properties of the
      films has been made. The electrical sheet resistance and resistivity of the
      implanted films are observed to increase with increasing rapid thermal annealing
      (RTA) time, while decreasing as the ion dose increases. Without any RTA process,
      the variation of the carrier density is insensitive to the ion dose. With the RTA
      process, however, the carrier density of the implanted films increases and
      approaches that of the un-implanted ZnO film as the ion dose increases. On the
      other hand, the carrier mobility is shown to decrease with increasing ion doses
      when no RTA process is applied. With the RTA process, however, there is almost no
      change in the mobility. We have achieved the optical transmittance as high as 87%
      within the visible wavelength range up to 800 nm. It is also demonstrated that
      the work function can be engineered by changing the ion dose during the ion
      implantation process. We have found that the work function decreases as the ion
      dose increases.

PMID- 18047110
TI  - Effect of the charge on the morphology of sodium salt form of the randomly
      sulfonated polystyrene ionomer cast onto silicon wafers.
AB  - The morphology of the sodium salt form of randomly copolymerized polystyrene
      sulfonate (Na-PSS) in water/THF(99/1 v/v) cast onto silicon wafers, was studied
      by using scanning electron microscope (SEM). The contents of the sulfonate repeat
      units in Na-PSS were 1.1, 2.4, 4.6, 10.8, and 15.6 mol%. Based on the observed
      SEM images, the morphology of the Na-PSS changed with increasing ionic group
      content. For 1.1 and 2.4 mol%, sphere-shaped aggregates were formed with average
      sizes of 90 nm and of 77 nm, respectively. For 4.6 mol% and 10.8 mol%, 20-30 nm
      sized aggregates were close-packed and fused together, resulting a surface with
      large roughness and ca. 10 nm-sized pores were formed. As the mol% increased to
      15.6, the surface became smoother and flat films were formed.

PMID- 18047111
TI  - Effect of copper doping on the crystal structure and morphology of 1D
      nanostructured manganese oxides.
AB  - We have tried to control the aspect ratio and physicochemical properties of 1D
      nanostructured manganese oxides through copper doping. Copper-doped manganese
      oxide nanostructures have been synthesized by one-pot hydrothermal treatment for
      the mixed solution of permanganate anions and copper cations. According to powder
      X-ray diffraction and electron microscopic analyses, all the present materials
      commonly crystallize with alpha-MnO2-type structure but their aspect ratio
      decreases significantly with increasing the content of copper. Such a variation
      of crystallite dimension is attributable to the limitation of crystal growth by
      the incorporation of copper ions. X-ray absorption spectroscopic studies at Mn K-
      and Cu K-edges clearly demonstrate that the average oxidation state of manganese
      ions is increased by the substitution of divalent copper ions. Electrochemical
      measurements reveal the improvement of the electrode performance of
      nanostructured manganate upon copper doping, which can be interpreted as a result
      of the decrease of aspect ratio and the increase of Mn valence state. From the
      present experimental findings, it becomes certain that the present Cu doping
      method can provide an effective way of controlling the crystal dimension and
      electrochemical property of 1D nanostructured manganese oxide.

PMID- 18047112
TI  - H2 uptake and synthesis of the Li-dispersed manganese oxide nanotubes.
AB  - Well aligned Li-dispersed manganese oxide nanotubes were prepared using LiNO3,
      Mn(NO3)2 x xH2O and an anodic aluminum oxide template by solvent-free method for
      potential applications in H2 storage. The obtained nanotubes were characterized
      by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission
      electron microscopy (TEM). The analyses revealed the Mn2O3 nanotubes to have a
      cubic structure with a uniform length, 40-50 nm in wall thickness and 250 +/- 10
      nm in the outer diameter. The level of H2 adsorption was determined using the
      gravimetric method. The Li-dispersed manganese oxide nanotubes showed a 0.26 wt%
      for the amount of hydrogen adsorption at 77 K under 4.5 MPa.

PMID- 18047113
TI  - Improved electrochemical performance of LiCoPO4 nanoparticles for lithium ion
      batteries.
AB  - Single phase LiCoPO4 nanoparticles were synthesized by solid-state reaction.
      LiCoPO4/Li batteries were fabricated in an argon-filled glove box, and their
      electrochemical properties were analyzed by cyclic voltammetry (CV) and charge
      discharge tests. The structural performance of LiCoPO4 nanoparticles was
      investigated by X-ray diffraction (XRD) and scanning electron microscope (SEM).
      The XRD result demonstrated that LiCoPO4 nanoparticles had an orthorhombic
      olivine-type structure with a space group of Pmnb. The charge-discharge tests
      indicated that the initial discharge capacity and coulombic efficiency of
      LiCoPO4/Li batteries were 110 mA h/g and 48% in cut-off voltage range of 3.0-5.3
      V, 90 mA h/g and 54% in cut-off voltage range of 3.0-5.1 V, 70 mA h/g and 60% in
      cut-off voltage range of 3.0-5.0 V, respectively. After 30 cycles, the coulombic
      efficiency was 78% for 3.0-5.3 V, 88% for 3.0-5.1 V, 91% for 3.0-5.0 V,
      respectively. These results indicated that the coulombic efficiency of LiCoPO4/Li
      battery increased upon cycling and upon decreasing in charge upper limit voltage,
      respectively.

PMID- 18047114
TI  - Investigation of potential alternative hydrogen carrier, Mg supported zeolite
      with temperature programmed desorption of NH3.
AB  - Magnesium ion exchanged zeolite A was subject to the measurement of the
      temperature programmed desorption of NH3 to explore the possibility of the
      potential hydrogen carrier. The result suggested that the Mg supported NaA
      zeolite released a significant amount of ammonia corresponding to 1.4 Hwt%
      hydrogen at around 373 K. Under the same condition after the NH3 adsorption at
      ambient temperature, the MgCl2 sample released 1.0 Hwt% hydrogen at around 340 K.
      The present work suggests that the Mg supported zeolite can also be utilized as
      hydrogen carrier.

PMID- 18047115
TI  - Microspherical poly(methyl methacrylate)/multiwalled carbon nanotube composites
      prepared via in situ dispersion polymerization.
AB  - In this study, microspherical poly(methyl methacrylate)/multi-walled carbon
      nanotube (PMMA/ MWCNT) composites were directly prepared by in situ dispersion
      polymerization using poly (N-vinylpyrrolidone) in methanol media. PMMA/MWCNT
      microspheres having a diameter of 2.6 approximately 3.9 microm and a molecular
      weight of 58,000 approximately 65,000 g/mol with a 15.7 approximately 19.5%
      coefficient of variation (Cv) were synthesized. The morphology of the synthesized
      composite was investigated using scanning electron microscopy and transmission
      electron microscopy. The experimental results demonstrated that MWCNTs are well
      dispersed and embedded in the final PMMA/MWCNT microspheres. The prepared
      PMMA/MWCNT microspheres were investigated in terms of their capacity to serve as
      an electrorheological (ER) materials.

PMID- 18047116
TI  - Multi-encoded rugate porous silicon as nerve agents sensors.
AB  - The nanostructured rugate porous silicons (PSi) containing multiple photonic band
      gaps have been generated by an electrochemical etching through applying a
      composite waveform summed three computer-generated pseudo-sinusoidal current
      waveforms. They exhibit three sharp photonic band gaps in the optical
      reflectivity spectrum, corresponding to the each of the sine components varied
      from 0.42, 0.36, and 0.30 Hz, with a spacing of 0.06 Hz between each sine
      component. The sensing experiments using multi-encoded rugate PSi for the
      detection of nerve agents such as triethyl phosphate (TEP), diethyl
      chlorophosphate (DCP), dimethyl methylphosphonate (DMMP), and diethyl
      ethylphosphonate (DEEP) have been achieved. Capillary condensation in the pores
      causes the reflectivity of rugate PSi to shift to longer wavelengths due to an
      increase in refractive indices of the porous medium.

PMID- 18047117
TI  - Multi-wavelength emitting InGan/GaN quantum well grown on V-shaped gan(1101)
      microfacet.
AB  - InGaN/GaN multiple quantum wells (MQWs) were successfully grown on the inclined
      GaN(1101) microfacets. Conventional photolithography and subsequent growth of GaN
      were employed to generate the V-shaped microfacets along (1120) direction. The
      well-developed microfacets observed by scanning electron microscopy and the clear
      transmission electron microscope interfacial images indicated that the MQW was
      successfully grown on the GaN microfacets. Interestingly, cathodoluminescence
      (CL) spectra measured on the microfacets showed a continuous change in the
      luminescence peak positions. The CL peaks were shifted to a longer wavelength
      from 420 nm to 440 nm as the probing points were changed along upward direction.
      This could be attributed to the nonuniform distribution of the In composition
      and/or the wavefunction overlapping between adjacent wells. Present works thus
      propose a novel route to fabricate a monolithic white light emitting diode
      without phosphors by growing the InGaN/GaN MQWs on (1101) facet.

PMID- 18047118
TI  - Nanocrystalline formation in immiscible Cu-Mo system subjected to mechanical
      alloying.
AB  - The mechanical alloying process has been studied on the Cu-Mo system, the atomic
      pair of which is characterized by a positive heat of mixing of +19 kJ/mol. The
      EXAFS and X-ray diffraction measurements have been employed to analyze the
      structural changes taking place during milling. Two phases mixture of
      nanocrystalline fcc-Cu and bcc-Mo with a grain size of 10 nm has been formed by
      MA of Cu30Mo70 powders for 200 hours. The structural analysis based on the EXAFS
      spectra revealed that bcc and fcc crystal structure clearly do not change around
      Mo and Cu atoms up to 200 h of milling, respectively. Studies of the
      thermodynamical considerations by DSC analyses confirmed that the alloying does
      not occur even after 200 hours of MA in Cu-Mo system.

PMID- 18047119
TI  - Nanosized hydroxyapatite powder synthesized from eggshell and phosphoric acid.
AB  - The present research describes synthesis of highly sinterable, nano-sized
      hydroxyapatite (HAp) powders using a wet chemical route with recycled eggshell
      and phosphoric acid as calcium and phosphorous sources. The raw eggshell was
      easily turned to CaO by the calcining process, and phosphoric acid was mixed with
      the calcined eggshell by the wet, ball-milling method. The crystalline
      development and microstructures of the synthesized powders and sintered samples
      were examined by X-ray diffractometry and scanning electron microscopy,
      respectively. The observed phases on the powder synthesis process were dependent
      on the mixing ratio (wt%) of the calcined eggshell to phosphoric acid and the
      heating temperature. The ball-milled, nano-sized HAp powder, which has an average
      particle size of 70 nm, was fully densified at 1300 degrees C for 1h. The Ca/P
      ratio for stoichiometric composition of HAp was controlled by adjustment of the
      mixing ratio.

PMID- 18047120
TI  - Optical properties of eu doped M-Ga2S4 (M: Zn, Ca, Sr) phosphors for white light
      emitting diodes.
AB  - Eu2+ doped M-thiogallate (MGa2S4, M: Zn, Ca, Sr) phosphors were prepared by solid
      state reaction. The dependence of luminescent properties, photoluminescence and
      cathodoluminescence, on M2+ ions was investigated. ZnGa2S4: Eu2+, CaGa2S4: Eu2+,
      and SrGa2S4: Eu2+ exhibited a green emission band at 540 nm, 560 nm, and 535 nm,
      respectively. The red-shift between CaGa2S4: Eu2+ and SrGa2S4: Eu2+ was
      originated from the radius difference of Ca2+ and Sr2+ ions. However, it did not
      apply to ZnGa2S4 : Eu2+ despite of smaller radius of Zn2+ ion. The particle size
      of ZnGa2S4 : Eu2+ was much smaller than those of the other thiogallates, leading
      to extremely low CL emission.

PMID- 18047121
TI  - Photocatalytic reduction of nitrate in wastewater using ZnO nanopowder
      synthesized by solution combustion method.
AB  - ZnO nanopowder was synthesized by a unique method which is called solution
      combustion method (SCM). This nanopowder was used for a photocatalyst to
      decompose nitrate that is a toxic pollutant in wastewater. It has been known that
      TiO2, the most popular photocatalyst, does not decompose the nitrate. In this
      paper, however, the SCM ZnO nanopowder decomposed about 13% of nitrate.
      Furthermore, adding methanol as a hole scavenger, the decomposition rate was
      enhanced by about 5 times. On the other hand, it has been reported that the
      photocatalytic reduction reaction of nitrate produces ammonia as a final product.
      The present results, however, suggest that the final product is non-toxic
      nitrogen gas rather than the toxic ammonia. These results would be very valuable
      for drinking water purification.

PMID- 18047122
TI  - Preparation of nanosized Pt-Au alloy catalyst and its activity in methanol
      oxidation.
AB  - The alloy catalyst has been widely used because it will be able to improve the
      activity and selectivity of the single metal catalyst in a given chemical
      reaction. In this study, the preparation and characteristics of nanosized Pt and
      Au particles on alumina and their catalytic activity were described. Nanosized Pt
      Au catalysts were prepared by impregnation (IMP) method and deposition (DP)
      method using alumina or ZnO/Al2O3 as support. The size of Pt and Au particles
      were observed by transmission electron microscopy (TEM), energy dispersive
      spectroscope (EDS), and X-ray diffraction (XRD). Catalytic activity for oxidation
      of methanol was measured using a flow reactor. It could be seen that the Pt
      particle size and dispersion in the alloy catalysts was rarely influenced by
      preparation methods and Au particles coated by deposition method were well
      dispersed. TEM images showed that Au particles were well dispersed in the
      Pt/Au/ZnO/Al2O3 catalyst of which Au particles was supported by deposition
      method. The catalytic activity for methanol are given in the order of Pt
      Au[IMP]/ZnO/Al2O3 > Pt[IMP]/Au[DP]/ZnO/Al2O3 > Au[DP]/Pt[IMP]/ZnO/Al2O3 > Pt
      Au[DP]/ZnO/Al2O3. Therefore, Au particle size was doing not play an important
      role in increasing the oxidation activity, but the Au particles may promote the
      methanol oxidation.

PMID- 18047123
TI  - Work function increase of Al-doped ZnO thin films by B+ ion implantation.
AB  - The work function of an Al-doped ZnO (AZO) thin film can be increased via B+ ion
      implantation from 3.92 eV up to 4.22 eV. The ion implantation has been carried
      out with the ion dose of 1 x 10(16) cm(-2) and ion energy of 5 keV. The
      resistance of the B+ implanted AZO films has been a bit raised, while their
      transmittance is slightly lowered, compared to those of un-implanted AZO films.
      These behaviors can be explained by the doping profile and the resultant band
      diagram. It is concluded that the coupling between the B+ ions and oxygen
      vacancies would be the main reason for an increase in the work function and a
      change in the other properties. We also address that the work function is more
      effectively alterable if the defect density of the top transparent conducting
      oxide layer can be controlled.

PMID- 18047124
TI  - Stress behavior of FCC metallic thin films during thermal evaporation.
AB  - The development of stress in metallic thin films, monitored by in-situ curvature
      measurements during deposition, is analyzed. Three distinct stress regions
      including initial compressive, broad tensile, and incremental compressive stress
      were reported in terms of the film thickness (deposition time) by F. Spaepen. An
      experimental set-up was assembled for the in-situ curvature measurements
      utilizing vacuum thermal evaporation and multi-beam laser reflection points
      arrayed in x- and y-axis. The change in the spacing of laser reflected points was
      converted to the curvature of specimen, in turn, to instantaneous stress levels
      in the growing films using Stoney's formula. To investigate the effect on the
      distinct stress regions, the flux of the depositing metallic atoms was used as an
      experimental variable in this study. For the lowest flux cases for Cu and Ag, an
      additional second compressive stress stages after tensile maximum stress was
      observed in this study. Initial compressive part and tensile maximum stress
      regions appeared in shorter period of time for the thin films deposited at higher
      flux of atoms. Thus the flux of depositing atoms may affect the mechanisms of
      each stage. The initial compressive stress is conjectured to stem from the state
      of thin film surfaces; dynamic and relaxed surface. A broad tensile region is
      reported from the fact that the reduction of excess volume associated with grain
      boundaries and/or the coalescence of grains for high mobility materials. The
      incremental compressive stress region may be related to surface state and atomic
      mobilities.

PMID- 18047125
TI  - Atomistic simulation of boron diffusion with charged defects and diffusivity in
      strained Si/SiGe.
AB  - We discuss the boron diffusion in a biaxial tensile strained {001} Si and SiGe
      layer with kinetic Monte Carlo (KMC) method. We created a strain in silicon by
      adding a germanium mole fraction in silicon in order to perform a theoretical
      analysis. The generation of a strain in silicon influences in the diffusivity as
      well as the penetration profile during the implantation. The strain energy for
      the charged defects has been calculated from the ab-initio calculation while the
      diffusivity of boron was extracted from the Arrhenius formula. Hereby, the
      influence of the germanium content on the dopant diffusivity was estimated. Our
      KMC study revealed that the diffusion of the B atoms was retarded with increasing
      Germanium mole fraction in a strained silicon layer. Furthermore, we derived a
      functional dependence of the in-plane strain as well as the out-of-plane strain
      on the germanium mole fraction, which lies in the distribution of equivalent
      stresses along the Si/SiGe interface.

PMID- 18047126
TI  - Equivalent circuit model of semiconductor nanowire diode by SPICE.
AB  - An equivalent circuit model of nanowire diodes is introduced. Because nanowire
      diodes inevitably involve a metal-semiconductor-metal structure, they consist of
      two metal-semiconductor contacts and one resistor in between these contacts. Our
      equivalent circuit consists of two Schottky diodes and one resistor. The current
      through the reverse-biased Schottky diode is calculated from the thermionic field
      emission (TFE) theory and that of the forward-biased Schottky diode is obtained
      from the classical thermionic emission (TE) equation. Our model is integrated
      into the conventional circuit simulator SPICE by a sub-circuit with TFE and TE
      routines. The results simulated with our model by SPICE are in good agreement
      with various, previously reported experimental results.

PMID- 18047127
TI  - Electron-phonon interaction model and prediction of thermal energy transport in
      SOI transistor.
AB  - An electron-phonon interaction model is proposed and applied to thermal transport
      in semiconductors at micro/nanoscales. The high electron energy induced by the
      electric field in a transistor is transferred to the phonon system through
      electron-phonon interaction in the high field region of the transistor. Due to
      this fact, a hot spot occurs, which is much smaller than the phonon mean free
      path in the Si-layer. The full phonon dispersion model based on the Boltzmann
      transport equation (BTE) with the relaxation time approximation is applied for
      the interactions among different phonon branches and different phonon
      frequencies. The Joule heating by the electron-phonon scattering is modeled
      through the intervalley and intravalley processes for silicon by introducing
      average electron energy. The simulation results are compared with those obtained
      by the full phonon dispersion model which treats the electron-phonon scattering
      as a volumetric heat source. The comparison shows that the peak temperature in
      the hot spot region is considerably higher and more localized than the previous
      results. The thermal characteristics of each phonon mode are useful to explain
      the above phenomena. The optical mode phonons of negligible group velocity obtain
      the highest energy density from electrons, and resides in the hot spot region
      without any contribution to heat transport, which results in a higher temperature
      in that region. Since the acoustic phonons with low group velocity show the
      higher energy density after electron-phonon scattering, they induce more
      localized heating near the hot spot region. The ballistic features are strongly
      observed when phonon-phonon scattering rates are lower than 4 x 10(10) S(-1).

PMID- 18047128
TI  - Fabrication and characterization of directly-assembled ZnO nanowire field effect
      transistors with polymer gate dielectrics.
AB  - We report the fabrication and electrical characterization of ZnO nanowire field
      effect transistors (FETs). Dielectrophoresis technique was used to directly align
      ZnO nanowires between lithographically prepatterned source and drain electrodes,
      and spin-coated polyvinylphenol (PVP) polymer thin layer was used as a gate
      dielectric layer in "top-gate" FET device configuration. The electrical
      characteristics of the top-gate ZnO nanowire FETs were found to be comparable to
      the conventional "bottom-gate" nanowire FETs with a SiO2 gate dielectric layer,
      suggesting the directly-assembled nanowire FET with a polymer gate dielectric
      layer is a useful device structure of nanowire FETs.

PMID- 18047129
TI  - Effect of TiO2 particle size on the performance of viologen-anchored TiO2
      electrochromic device.
AB  - The effect of TiO2 particle size on the performance of the electrochromic device
      (ECD) has been investigated in this work by applying the TiO2 nanoparticles in 7,
      15, and 30 nm sizes. The phosphonated viologen, bis(2-phosphonoethyl)-4,4'
      bipyridinium dibromide, was anchored on the TiO2 surfaces for the construction of
      ECD. The ECD derived from 7 nm-sized TiO2 demonstrated the highest contrast ratio
      with high optical transparency, whereas it showed the slowest switching response.
      The enhancement of coloration efficiency with decrease of TiO2 particle size is
      due to the increased amount of the anchored viologen on TiO2 electrode. On the
      other hand, the relatively slower switching response would be caused by the
      difficulty of diffusion for the electrolytes and counter-ions through the small
      pores of the nanocrystalline TiO2 electrode derived from 7 nm-sized
      nanoparticles.

PMID- 18047130
TI  - Spin-polarized current of a transistor in single Mn12 molecular magnets.
AB  - Focusing on the framework of how to realize the molecular spintronics in a single
      molecular magnet, we present theoretical studies on the spin-polarized quantum
      transport behavior through a single Mn12 molecular magnet. Our theoretical
      results were obtained by carrying out density functional theoretical calculation
      within the Keldysh nonequilibrium Green function formalism. The ultimate goal of
      the molecular spintronics is to develop single molecule transistors which
      generate spin-polarized currents through the molecular magnet. We obtained the
      density of states, the transmission coefficients and the characteristic features
      of the current-voltage (I-V) on the spin-polarized transport properties of Mn12
      by the theoretical calculation. These results show the possibility for the
      realization of molecular spintroinics using single molecular magnets.

PMID- 18047132
TI  - New adders using hybrid circuit consisting of three-gate single-electron
      transistors (TG-SETs) and MOSFETs.
AB  - A half-adder (HA) and a full-adder (FA) using hybrid circuits combining three
      gate single-electron transistors (TG-SETs) with metal-oxide-semiconductor field
      effect-transistors (MOSFETs) are proposed. The proposed HA consists of three TG
      SETs, two enhanced-mode NMOSFETs, and two depletion-mode NMOSFETs, and the
      proposed FA consists of eight TG-SETs, two enhanced-mode NMOSFETs, and two
      depletion-mode NMOSFETs. The complexities in the HA and the FA are 7 and 12,
      respectively, and the worst-case delays in the HA and the FA are 1.48 ns and 2.25
      ns, respectively. Compared with the conventional CMOS FA with 0.35 microm
      technology, the proposed FA can be constructed with 0.43 of devices, and can
      operate with 3.5 of worst-case delay, 1/534 of average power consumption, and
      1/152 of power-delay-product (PDP). The proposed HA and FA can be operated as a
      half-subtractor (HS) and a full-subtractor (FS) in the case when the levels of
      the control gates in the HA and the FA are fitly determined. The basic operations
      of the proposed HA and the proposed FA have been successfully confirmed through
      SPICE circuit simulation based on the physical device model of TG-SETs.

PMID- 18047131
TI  - Charge-transfer interaction in single-walled carbon nanotubes with
      tetrathiafulvalene and their applications.
AB  - We observed that single-walled carbon nanotube (SWNT) was aligned in the presence
      of TTF This alignment was induced by a specific interaction between SWNT and
      tetrathiafulvalene (TTF), a well-known organic donor. The interaction between the
      two molecules can be explained by a charge-transfer, which was confirmed by X-ray
      photoelectron spectroscopy (XPS) and Raman spectroscopy. The binding energies of
      S (2P1/2) and S (2P3/2) were shifted from 163.0 eV and 164.1 eV to 163.9 eV and
      165.1 eV, respectively. In Raman spectra of the SWNT-TTF, three peaks of SWNT in
      radial breathing mode were also upshifted by 4-5 cm(-1). The charge-transfer
      interaction also contributed in modifying the electronic structure of SWNT and
      furthermore enhanced the electrical conductivity of SWNT. A more conductive thin
      film was fabricated using the SWNT-TTF Four-probe measurement revealed that the
      surface resistance of the SWNT-TTF film was reduced to 4.359 omega at room
      temperature while that of SWNT film was 6.894 omega. These results enable carbon
      nanotubes to be utilized more for practically for industrial applications in
      fabricating peculiar nano-sized building blocks.

PMID- 18047133
TI  - Extremely scaled 3-dimensional multiple-gate technologies for terabit era.
AB  - In order to make possible silicon-based, room-temperature operable devices having
      a feature size in the sub-5 nm range, an all-around gate FinFET having an
      extremely narrow gate-surrounded silicon fin with a floating body was proposed
      and fabricated. Sub-10 nm device issues such as short channel effects,
      punchthrough, source/drain series resistance, gate misalignment, and hot-carrier
      injection were intensively studied and optimized for the sub-5 nm structure. The
      sub-5 nm all-around gate FinFET with 3 nm fin width and 1.2 nm EOT was
      demonstrated for the first time.

PMID- 18047134
TI  - Enhanced contrast of electrochromic full cell systems with nanocrystalline PEDOT
      prussian blue.
AB  - Poly-(3,4-ethylenedioxythiophene) (PEDOT) is an ideal polymer for electrochromic
      (EC) devices due to its fast response time, high conductivity, and facile
      fabrication in a doped form except its demerit like an optical contrast
      limitation. In this study, we developed a simple way to overcome low coloration
      efficiency of PEDOT through fabricating a complementary PEDOT and prussian blue
      full cell system. Fundamental properties of EC displays, such as optical
      contrast, coloration efficiency, and switching speed, could be successfully
      optimized by controlling the deposition time and applied voltage during EDOT
      polymerization. In particular, UV transmittance spectra indicated that the
      optical contrast was enhanced up to 31 approximately 99% at the wavelength of 600
      nm. Scanning electron microscopy images showed that the optimized PEDOT and
      prussian blue films were deposited on ITO glass substrate with an uniform
      thickness of approximately 180 nm and approximately 190 nm, respectively.
      Moreover, according to the circuit analysis, the average response time of
      electric current for the optimized full cell system was about 400 ms. It is,
      therefore, concluded that such a full cell system could have high potential
      applications as smart windows and/or optical devices.

PMID- 18047135
TI  - Quantum mechanical device modeling: FinFET having an isolated n+/p+ gate region
      strapped with poly-silicon.
AB  - In this paper, we present our numerical study on FinFET having an isolated n+/p+
      gate region strapped with metal and poly-silicon structure. Our theoretical work
      is based on 2-D quantum-mechanical simulator with a self-consistent solution of
      Poisson-Schrodinger equation. Our numerical simulation revealed that the
      threshold voltage (VT) is controlled within -0.1 approximately +0.2 V with
      varying the doping concentration of the n+ and p+ polysilicon gate region from
      1.0 x 10(17) to 1.0 x 10(18) cm(-3). We also confirmed that the better VT
      tolerance of the FinFET on the variation of the fin thickness can be expected
      over the conventional FinFET structure. For instance, the VT of the FinFET under
      this work exhibited 0.02 V tolerance with respect to the variation of the fin
      thickness change of 5 nm (from 30 to 35 nm) while the traditional FinFET
      demonstrates the tolerance of 0.12 V for the same variation of the fin thickness.

PMID- 18047136
TI  - Resistance switching characteristics of HfO2 film with electrode for resistance
      change random access memory.
AB  - The electrode dependent resistance switching behaviors of amorphous HfO2 films
      grown by atomic layer deposition were systematically investigated. The low and
      high resistance states were successfully achieved for all the metal-insulator
      metal resistor systems with Mo, Ru, and Pt symmetric electrodes. The
      characteristic reset and set voltages as well as the dynamic resistance ratio of
      the resistor device are strongly dependent on the electrode material with
      different work function. In addition, the different features for switching
      voltages with electrode are shown with annealing temperature.

PMID- 18047137
TI  - Spin transport in spin filtering magnetic tunneling junctions.
AB  - Taking into account spin-orbit coupling and s-d interaction, we investigate spin
      transport properties of the magnetic tunneling junctions with spin filtering
      barrier using Landauer-Buttiker formalism implemented with the recursive
      algorithm to calculate the real-space Green function. We predict completely
      different bias dependence of negative tunnel magnetoresistance (TMR) between the
      systems composed of nonmagnetic electrode (NM)/ferromagnetic barrier
      (FB)/ferromagnet (FM) and NM/FB/FM/NM spin filtering tunnel junctions (SFTJs).
      Analyses of the results provide us possible ways of designing the systems which
      modulate the TMR in the negative magnetoresistance regime.

PMID- 18047138
TI  - Behavior characteristics of nano-stage according to hinge structure.
AB  - Nano-stages are used in many ultra-precision systems, such as scanning probe
      microscope (SPM), optical fiber aligners, ultra-precision cutting, measuring and
      optical systems. Generally, ultra-precision machining and measuring are achieved
      using a nano-scale motion stage actuated using Piezo-electric actuators (PZT),
      and the importance of and demands for the motion stage increase with the need to
      improve system performance and accuracy. However, it is difficult to find
      solutions because the performance and characteristics of nano-scale motion stages
      are determined by various factors, such as the hinge structure, actuator, and
      method of system control. This paper focuses on improving of leafspring and
      planar joint hinges, and suggests a composite joint hinge stage.

PMID- 18047139
TI  - Fabrication of poly-silicon nano-wire transistors on plastic substrates.
AB  - We report the fabrication and characterization of poly-Si nanowire transistors on
      flexible substrates. The nanowire transistors are fabricated on a SiO2/Si
      substrate using conventional CMOS processes, and then they are transferred onto
      polyimide substrates. The transfer process is performed by spin-coating of
      polyimide, curing (annealing) of the polyimide layer, and removal of the SiO2
      sacrificial layer. The optimized curing condition results in the maximum bending
      of 150 degrees with full recovery. The nanowire transistors exhibit transistor
      characteristics as a function of the backgate bias. Our new process can be
      applied to the fabrication of Si-nanowire transistors with larger mobilities.

PMID- 18047140
TI  - Device optimization of CO2 gas sensor using planar technology.
AB  - A planar type Li+ ion based potentiometric CO2 micro gas sensor of size 2 x 3 mm
      has been fabricated on alumina substrate by combining thin and thick film
      technology. The heater, electrodes and electrolyte were deposited by thin film
      deposition technique and the sensing and reference electrodes were printed by
      silk screen printing technology. The optimal thickness and sintering temperature
      of electrolyte are 1.2 microm and 775 degrees C. The sensor with Li2CO3 and 20
      mol% BaCO3 not only exhibits a good Nernstian behavior but also consistent
      results over a long time at 450 degrees C in dry as well as 70% RH humidity
      condition between 160-5000 ppm CO2 concentrations. The spreading effect of the
      sensing and reference materials was controlled by the addition of Al2O3:B2O3 (1:2
      mol%) glass.

PMID- 18047141
TI  - Novel synthesis of nanorod ZnO and Fe-doped ZnO by the hydrolysis of metal
      powders.
AB  - Fe-doped ZnO nanorods have been synthesized by a novel process employing a
      hydrolysis of metal powders. Zn and Fe nano-powders were used as starting
      materials and incorporated into distilled water. The solution was refluxed at 60
      degrees C for 24 h to obtain the precipitates from the hydrolysis of Zn and Fe. X
      ray diffraction patterns for all the samples showed a pure wurtzite single phase,
      without any segregation of the Fe into the particulates within the instrumental
      resolution limit. The TEM results for ZnO with and without an Fe-doping showed
      that the produced powders had a rod-like shape. The rod shape was attributable to
      the zinc oxide from the hydrolysis of Zn. With an increasing Fe content, the UV
      vis spectra were shifted to a long wave length and this result indicates that the
      band gap was changed by an Fe-doping.

PMID- 18047142
TI  - Fabrication of 3D functionalized microstructure via scanning probe lithography
      and self-assembly methods.
AB  - A type of 2-dimensional planar pattern with spatial resolution can be easily
      produced using scanning probe lithography (SPL). However, it has not been used
      successfully for fabricating 3-dimensional (3D) structures due to the low aspect
      ratio of the resulting structure. Herein, we describe a method for fabricating a
      3D functionalized structure via a combination of SPL and self-assembly
      techniques. In this study, a 3D structure was established on a Si surface with a
      passivated monolayer via SPL. The patterned layer was modified using a omega
      functionalized organosilane. Lateral force microscopy (LFM) was applied to
      discriminate the chemical functionalities and gold nanoparticles were also used
      to clearly identify the modified layer.

PMID- 18047143
TI  - Photonic polymer replicas from distributed Bragg reflectors structured porous
      silicon.
AB  - Well defined 1-dimentional (1-D) photonic crystals of polymer replicas have been
      successfully obtained. DBR porous silicon containing nanometer-scale pores are
      prepared by an anodic electrochemical etch of p(++)-type silicon wafer. The
      resulting DBR porous silicon film removed from the substrate by applying an
      electropolishing current has been thermally oxidized in the furnace at 400
      degrees C for 3 h. Oxidized DBR PSi/polystyrene composite films are prepared by
      casting of polymer solution onto a free-standing porous silicon photonic crystal
      layer. Flexible photonic polymer replicas have been prepared after the removal of
      oxidized DBR PSi matrix in HF/H2O mixture solution. Polymer replicas exhibit a
      sharp resonance in the reflectivity spectrum. Optical characteristics of photonic
      polymer replica indicate that the surface of polymer film has a negative
      structure of DBR PSi. This replica is stable in aqueous solutions for several
      days without any degradation.

PMID- 18047144
TI  - Characterization of intrinsic a-Si:H films prepared by inductively coupled plasma
      chemical vapor deposition for solar cell applications.
AB  - The hydrogenated amorphous silicon (a-Si:H) films, which can be used as the
      passivation or absorption layer of solar cells, were prepared by inductively
      coupled plasma chemical vapor deposition (ICP-CVD) and their characteristics were
      studied. Deposition process of a-Si:H films was performed by varying the
      parameters, gas ratio (H2/SiH4), radio frequency (RF) power and substrate
      temperature, while a working pressure was fixed at 70 m Torr. Their
      characteristics were studied by measuring thickness, optical bandgap (eV),
      photosensitivity, bond structure and surface roughness. When the RF power and
      substrate temperature were 300 watt and 200 degrees C, respectively, optical
      bandgap and photosensitivity, similar to the intrinsic a-Si:H film, were
      obtained. The Si-H stretching mode at 2000 cm(-1), which means a good quality of
      films, was found at all conditions. Although the RF power increased up to 400
      watt, average of surface roughness got better, compared to a-Si:H films deposited
      by the conventional PECVD method. These results show the potential for developing
      the solar cells using ICP-CVD, which have the relatively less damage of plasma.

PMID- 18047145
TI  - Carbon nanotube patterning with capillary micromolding of catalyst.
AB  - Patterning of multi-walled carbon nanotube (MWNT) in a plasma enhanced chemical
      vapor deposition (PECVD) chamber has been achieved by catalyst patterning using
      capillary micromolding process. Iron acetate catalyst nanoparticles were
      dissolved in ethanol and mold was fabricated with polydimethylsiloxane (PDMS).
      The ethanol solution containing catalyst nanoparticles was filled into the
      microchannel formed between PDMS mold and Si-wafer by capillary force. The
      capillary action of different solvents was simulated by commercial CFD-ACE+
      simulation code to determine optimal solvents. Simulated result shows that the
      choice of solvent was critical in this capillary filling process. After the
      catalyst patterning, MWNT was grown at 700 approximately 800 degrees C by PECVD
      process using CH4 and Ar gas in a scale of approximately 10 micro-meters in a
      tubular inductively coupled plasma reactor. Grown CNTs were analyzed by FE-SEM
      and Raman Spectroscopy.

PMID- 18047146
TI  - Characteristics of nanocomposite ZrO2/Al2O3 films deposited by plasma-enhanced
      atomic layer deposition.
AB  - Nanocomposite ZrO2/Al2O3 (ZAO) films were deposited on Si by plasma-enhanced
      atomic layer deposition and the film characteristics including interfacial oxide
      formation, dielectric constant (k), and electrical breakdown strength were
      investigated without post-annealing process. In both the mixed and nano-laminated
      ZAO films, the thickness of the interfacial oxide layer (T(IL)) was considerably
      reduced compared to ZrO2 and Al2O3 films. The T(IL) was 0.8 nm in nano-composite
      films prepared at a mixing ratio (ZrO2:Al2O3) of 1:1. The breakdown strength and
      the leakage current level were greatly improved by adding Al2O3 as little as 7.9%
      compared to that of ZrO2 and were enhanced more with increasing content of Al2O3.
      The k of ZrO2 and mixed ZAO (Al2O3 7.9%) films were 20.0 and 16.5, respectively.
      These results indicate that the addition of Al2O3 to ZrO2 greatly improves the
      electrical properties with less cost of k compared to the addition of SiO2.

PMID- 18047147
TI  - Electrical properties of polyaniline and multi-walled carbon nanotube hybrid
      fibers.
AB  - We have fabricated for the first time one-dimensional multiwalled carbon nanotube
      (MWNT) nanocomposite fibers with improved electrical properties using
      electrospinning. Polyaniline (PANi) and poly(ethylene oxide) (PEO) were used as a
      conducting and a nonconducting matrix, respectively, for hybrid nanofibers
      including MWNTs. The hybrid nanofibers fabricated by electrospinning had a length
      of several centimeters and a diameter ranging from approximately 100 nm to
      approximately 1 microm. Transmission electron microscopic analysis confirmed that
      the MWNTs were successfully oriented along the fiber axis without any severe
      aggregation during electrospinning. The hybrid nanofibers showed an enhanced
      electrical conductance with increasing MWNT content up to 0.5 wt%, and compared
      to PANi/PEO fibers, they also showed a stable linear ohmic behavior. These hybrid
      conducting nanofibers can be applied to chemical and biosensors that require a
      high sensitivity.

PMID- 18047148
TI  - Effect of pre-existing oxide film on the electrochemical fabrication of
      nanoporous alumina film.
AB  - Different thickness of barrier-type oxide film was intentionally grown on the Al
      metal surface and the effect of barrier film on the formation of nanoporous
      aluminum oxide film during anodization was investigated to control the nanopore
      structure. Analysis of potential transients during anodization indicated that
      anodic oxide film is initially overlaid on the barrier film but the anodic film
      is more facile to dissolve than barrier film. As the thickness of barrier film
      increases, both nanopore diameter and density decrease but the pore length is
      irrespective of barrier-film thickness.

PMID- 18047149
TI  - Electrochemical fabrication of SrTiO3 nanowires with nanoporous alumina template.
AB  - Strontium titanate nanowires were electrochemically synthesized with nanoporous
      alumina template. Both chemical and electrical variables such as electrolyte pH,
      temperature, and current waveform were modulated to investigate the synthesis
      process of SrTiO3 nanowires. Superimposed cathodic pulse and diffusion time
      accelerated the growth of SrTiO3 nanowires, which suggested that the
      concentration of H+ and Sr2+ ion inside alumina template had a strong influence
      on the formation of SrTiO3 nanowires. Morphology and crystallinity of SrTiO3
      nanowires were investigated with scanning electron microscope, X-ray
      diffractometer and energy dispersive X-ray spectroscopy.

PMID- 18047150
TI  - Fabrication of mesoporous cerium dioxide films by cathodic electrodeposition.
AB  - Mesoporous cerium dioxide (Ceria, CeO2) thin films have been successfully
      electrodeposited onto ITO-coated glass substrates from an aqueous solution of
      cerium nitrate using CTAB (Cetyltrimethylammonium Bromide) as a templating agent.
      The synthesized films underwent detailed characterizations. The crystallinity of
      synthesized CeO2 film was confirmed by XRD analysis and HR-TEM analysis, and
      surface morphology was investigated by SEM analysis. The presence of mesoporosity
      in fabricated films was confirmed by TEM and small angle X-ray analysis. As
      synthesized film was observed from XRD analysis and HR-TEM image to have well
      crystallized structure of cubic phase CeO2. Transmission electron microscopy and
      small angle X-ray analysis revealed the presence of uniform mesoporosity with a
      well-ordered lamellar phase in the CeO2 films electrodeposited with CTAB
      templating.

PMID- 18047151
TI  - Fabrications of nanofibers as crossed arrays by electrospinning.
AB  - We have developed a new method for obtaining nanofiber crossed arrays by
      exploiting an auxiliary electrode subjected to electrical frequencies, between
      the capillary tip and the grounded target in an electrospinning machine. The
      frequencies generated crossed arrays on a flat collector, used instead of a
      rotating wheel because of intersecting jets. We observed many straight and
      crossed structures. We determined the variation in morphology with changes in
      frequency, and characterized the samples using optical microscopy and a field
      emission scanning electron microscope. This paper reports on a simple, easy
      method for generating crossed array nanofibers on a flat substrate using
      electrical frequency in an auxiliary electrode.

PMID- 18047152
TI  - Reduction of interpore distance of anodized aluminum oxide nano pattern by mixed
      H3PO4:H2SO4 electrolyte.
AB  - A self-formed and ordered anodized aluminum oxide (AAO) nano pattern has
      generated considerable interest in both scientific research and commercial
      application. However, the interpore distance obtainable by AAO is limited by 40
      500 nm depending on electrolyte and anodizing voltage. It's believed that below
      30 nm AAO pattern is a key technology in the fabrication semiconductor nano
      structures with enhanced quantum confinement effect, so we worked on the
      reduction of interpore distance of AAO with a novel electrolyte. AAO nano
      patterns were fabricated with mixed H2SO4 and H3PO4 as an electrolyte for various
      voltages and temperatures. The interpore distance and pore diameter of AAO were
      decreased with reduced anodizing voltage. As a result, an AAO nano pattern with
      the interpore distance of 27 nm and the pore diameter of 7 nm was obtained. This
      is the smallest pattern, as long as we know, reported till now with AAO
      technique. The fabricated AAO pattern could be utilized for uniform and high
      density quantum dots with increased quantum effect.

PMID- 18047153
TI  - Study on fracture behavior of surface treated montmorillonite/epoxy
      nanocomposites.
AB  - It is known that the mechanical properties of clay-reinforced nanocomposites are
      significantly affected by the dispersion of clay particles in the matrix. In this
      study, the effect of surface-treatment of Montmorillonite (MMT) on the fracture
      behavior of MMT/epoxy nanocomposite was investigated. For this purpose, fracture
      tests were performed using samples with three different clay concentration level.
      After fracture tests, SEM analysis was made on the fracture surfaces to examine
      the fracture mechanism. It was found that the MMT treatment using 3
      aminopropyltriethoxysilane enhanced the fracture toughness increased of the
      MMT/epoxy nanocomposite. This is due to the improved intercalation effect and
      interfacial strength between MMT and epoxy matrix.

PMID- 18047154
TI  - Bio-inspired cell concentration and deformability monitoring chips.
AB  - The paper presents a couple of biofluidic devices, whose functions are inspired
      from biological cell concentration and deformability monitoring functions. The
      cell concentration monitoring chip is inspired from RBC control mechanism in
      kidney, performing cell concentration monitoring functions. The cell
      deformability chip, inspired from selective RBC destruction mechanism in spleen,
      performs mechanical cell deformability monitoring functions. The structures and
      principles of the bio-inspired chips are presented and compared with those of the
      biological organs. The unique features and performance characteristics of the bio
      inspired chips are analyzed and verified from experimental study. The bio
      inspired cell concentration monitoring chips perform flow-rate insensitive
      concentration measurement, while the bio-inspired cell deformability monitoring
      chips achieve size-independent cell deformability measurement. Common advantages
      of the bio-inspired chips include simple structures, digital signals and high
      integrability, thus making them suitable for use in integrated digital biomedical
      systems.

PMID- 18047155
TI  - Place and health research in Canada.

PMID- 18047156
TI  - Unpacking income inequality and population health: the peculiar absence of
      geography.
AB  - BACKGROUND: A large and growing body of literature investigating the negative
      relationship between income inequality and population health (at different
      geographic scales) has developed over the past several years, although the
      relationship is not universal apparently. We argue that there has been a peculiar
      absence of geography in studies of the relationship between income inequality and
      population health and that explanations for the mixed results have been hampered
      by an inattention to geography. METHODS: Using methods of spatial pattern
      visualization, outlier analysis and comparative case study analysis, we
      investigate the role of "geography" as a means of "unpacking" the relationship
      between income inequality and health in Canada and the United States. RESULTS:
      The findings demonstrate how analyzing the study of income inequality and
      population health in the context of place makes otherwise obscure patterns
      visible and opens up new questions and opportunities for investigating how
      unequal places may be less healthy than more egalitarian ones. Rather than
      dismissing the importance of income inequality and health because it does not
      appear to exist at all times and in all places, we raise questions such as: Under
      what conditions does the relationship between income inequality and population
      health hold? and What, if anything, is similar about places where it does (or
      does not) hold? as crucial questions requiring a different kind of analysis than
      has been common in this literature. CONCLUSION: We recommend that place and
      health studies seek this balance between universalistic and particularistic
      explanations of place and health relationships in order to best understand the
      socio-geographic production of health.

PMID- 18047157
TI  - Conceptualizing and operationalizing neighbourhoods: the conundrum of identifying
      territorial units.
AB  - BACKGROUND: Over the past 10 years, there has been a surge of interest in
      studying small-area characteristics as determinants of population and individual
      health. Accumulating evidence indicates the existence of variations in the health
      status of populations living in areas that differ in affluence and shows that
      selected small-area characteristics are associated with the occurrence of
      selected health behaviours. These variations cannot be attributed solely to
      differential characteristics of populations living within small areas. One vexing
      problem that confronts researchers is that of conceptualizing and
      operationalizing neighbourhoods through delineation of small territorial units in
      health research. GOALS AND METHODS: The aims of this paper are to selectively
      overview conceptual definitions of neighbourhoods and to illustrate the
      challenges of operationalizing neighbourhoods in urban areas by describing our
      attempts to map out small territorial units on the Island of Montreal and in the
      City of Calgary. CONCLUSION: We outline guiding principles for the construction
      of a methodology for establishing small-area contours in urban areas and
      formulate recommendations for future research.

PMID- 18047158
TI  - Does choice of spatial unit matter for estimating small-area disparities in
      health and place effects in the Vancouver Census Metropolitan Area?
AB  - BACKGROUND: The purposes of this study were to determine (i) the extent to which
      small-area estimates of self-rated health are dependent upon the choice of areal
      unit and measure of socio-economic (SES) status, and (ii) the extent to which
      place effects on self-rated health are dependent upon the choice of areal unit
      and measure of SES. METHODS: The data were obtained from a subset of respondents
      in the Canadian Community Health Survey 2.1 (2003) aged 18 to 74 residing in the
      Vancouver Census Metropolitan Area. General health status was estimated using an
      item assessing respondents' self-rated health. Small-area data were obtained from
      the Statistics Canada 2001 Census at two spatial levels: larger Census Tract (CT)
      (average population 2,500-8,000) and smaller Dissemination Area (DA) (average
      population 400-700). SES quintiles were constructed using median family income
      and two indices. Hierarchical non-linear modelling was used to test for place
      effects. RESULTS: A gradient was found of increasing prevalence of "fair or poor"
      self-rated health by decreasing SES quintile at both the DA and CT level. With
      age category, sex, family income and education controlled for, hierarchical
      analysis showed that compared with living in a high SES CT or DA the odds of
      reporting fair or poor self-rated health increased for respondents living in the
      lowest quintile CT or DA. INTERPRETATION: Aggregation using DAs or CTs produces
      only small differences in estimates of fair or poor self-rated health by
      quintiles of SES. Gradients are somewhat stronger for DAs. Place effects are
      somewhat stronger for deprivation indices than the measure of median income.

PMID- 18047159
TI  - Predictors of psychological distress in low-income populations of Montreal.
AB  - THEORETICAL PERSPECTIVE: Many epidemiologic studies agree that low-income
      populations are the groups most vulnerable to mental health problems. However,
      not all people in economic difficulty show symptoms, and it appears that having a
      social support network plays a role in protecting against the chronic stress
      resulting from conditions such as poverty. OBJECTIVES: The aim of the study is to
      clarify the relative contribution of social support to the mental health of low
      income populations in two neighbourhoods in the southwest of Montreal: Pointe
      Saint Charles and Saint-Henri. METHODS: A random sample of 416 social assistance
      recipients in southwest Montreal and another sample of 112 people, drawn at
      random from the general population, were interviewed. The psychological distress
      scale used was the Indice de detresse psychologique--Enquete Sante Quebec
      (IDPESQ). The availability of social support components was assessed by using the
      Social Provisions Scale. Data were collected during interviews in the
      respondents' homes. Social support measures were entered into a multidimensional
      model including many variables identified as being associated with mental health.
      Multiple regression analysis identified the best predictors of psychological
      distress for the low-income population. FINDINGS AND CONCLUSIONS: Among the 30
      variables included in a multiple regression analysis, emotional support and the
      presence of persons perceived as stressful together accounted for most of the
      variance in distress predicted by the model. Although younger people, people
      experiencing food insecurity and people with poorer numeracy show a higher level
      of distress, these variables make a fairly marginal contribution compared with
      that of social relations.

PMID- 18047160
TI  - Living environments and health at the local level: the case of three localities
      in the Quebec city region.
AB  - BACKGROUND: To arrive at a better understanding of the combined impact of social
      health determinants on health inequities a research project was carried out in
      three localities in the Quebec city region. This paper aims to show how
      residents' health status and health determinants can be explored through various
      data sources and analytic perspectives, and how these can then be combined to
      create a more comprehensive picture of health status at the local level. METHODS:
      A multidisciplinary approach was adopted. Both quantitative and qualitative
      methods were used: information from databases entered into a geographic
      information system, telephone survey and face-to-face interviews with key
      informants, telephone surveys with representative samples of the population in
      each locality and in-depth interviews with citizens. The localities were
      subdivided into neighbourhood units to refine the analysis on local environment.
      RESULTS: The results obtained in the locality of Saint-Louis, which displays the
      worst scores of the three localities, illustrate the research strategy's
      potential. Socio-economic and health indicators show that Saint-Louis is less
      well-off than the two other localities and that huge disparities among
      neighbourhoods are present within this locality. Results from the interviews with
      key informants, the telephone survey and interviews with citizens confirm this
      overall picture, raising many hypotheses about the various factors interacting to
      contribute to levels of health. INTERPRETATION: Two main methodological
      conclusions can also be drawn from this study: that defining the appropriate
      spatial scale to study the impact of living environments is crucially important,
      and that a life course approach is essential to understanding how inequities
      develop.

PMID- 18047161
TI  - Neighbourhood, family and health care.
AB  - OBJECTIVE: The effects of family and place on health outcomes may be seriously
      misestimated by standard analytic techniques. The information-rich settings in
      several Canadian provinces can provide appropriate designs to minimize biases
      resulting from omitted variables and measurement error. This paper compares
      siblings with children living in the same neighbourhood (but not in the same
      family) in terms of health care utilization and health care costs. A complete
      history of residential mobility since birth permits an estimate of the effects of
      exposure to different environments. METHODS: Registry data from a Manitoba cohort
      born between 1978 and 1985 and continuously resident in the province generated a
      large sample of same-sex siblings and neighbours (N = 18,280). Administrative
      information on physician billings, hospital inpatient stays, and costs provided
      data on utilization between ages 12 and 17. RESULTS: Large effects on the outcome
      variables were associated with being in the same family (correlations up to
      0.50), whereas the correlations representing upper limits on neighbourhood
      effects were usually small. These neighbourhood correlations typically shrank
      slightly after adjustment for family effects. Higher neighbour correlations with
      utilization (particularly ambulatory visits) occurred in rural Manitoba and
      probably reflect variation in access to care. Higher correlations are associated
      with relatively small neighbourhoods and with families remaining in the
      neighbourhood for at least 17 years. DISCUSSION: Although specific variables
      taken from administrative data are only marginally predictive, our results
      emphasize the importance of "family" in affecting health care utilization in
      Manitoba. The minimal effects of neighbourhood differ from those found by
      investigators generally using weaker designs and emphasizing the significance of
      neighbourhood.

PMID- 18047162
TI  - Non-communicable disease and injury-related mortality in rural and urban places
      of residence: a comparison between Canada and Australia.
AB  - BACKGROUND: Few published studies looking at cross-national comparisons of rural
      urban health status are available. As a first step towards addressing the lack of
      information on how rural populations in Canada compare with rural populations
      elsewhere in the world, this paper examines and contrasts Canadian mortality
      risks of selected diseases in rural and urban areas with those of Australia.
      METHODS: Age-standardized mortality ratios for selected causes of deaths were
      calculated at the national level and broken down into place of residence
      categories using country-specific definitions of rurality (Metropolitan Influence
      Zones in Canada and the Australian Standard Geographical Classification [ASGC]
      Remoteness in Australia). RESULTS: Patterns of rural-urban mortality risk were
      mostly similar in both countries. However, depending on the causes of death
      examined, important differences were found. Mortality from motor vehicle
      accidents, suicide and a few cancer sites showed similar urban-rural gradients in
      both Canada and Australia. Notable differences were found for diabetes, all
      cancers combined, as well as lung and colorectal cancer. Rural Australians were
      at higher risk of dying from these diseases than their urban counterparts,
      whereas rural Canadians were at lower risk than urban Canadians. DISCUSSION:
      Overall, the patterns that have emerged from this comparison of Canadian and
      Australian mortality risks suggest that health status disparities between rural
      and urban populations are not limited to a specific country or region of the
      world. However, there are also important differences between the two countries,
      as the geographic mortality patterns varied according to sex and according to
      disease category. This analysis is an initial step in promoting discussion of
      rural health in an international context.

PMID- 18047163
TI  - Bridging place-based research and action for health.
AB  - This paper takes a population health planning and policy view of the issues in
      place and health raised by the research articles in this collection. The planning
      and policy issues are reducing health inequities and strengthening
      neighbourhoods. Regardless of the state of the art of place and health research,
      targeted social investments are being made to support neighbourhood
      infrastructure and community mobilization for place-based poverty reduction and
      community well-being in places across Canada. "Vibrant Communities", "Action for
      Neighbourhood Change" and other priority community initiatives provide an
      opportunity for intensive neighbourhood-based action research and future dialogue
      that will further advance theory and action on place and health.

PMID- 18047165
TI  - Now and then: the return of the matron.

PMID- 18047164
TI  - Geographic information systems (GIS) in the health field: an opportunity to
      bridge the gap between researchers and administrators.
AB  - This article starts by presenting some of the difficulties encountered by
      researchers and administrators in trying to work together. It then assesses the
      importance of the notion of territory in the planning and organization of health
      services. Last, the article presents the work achieved by the Agence de la sante
      de Montreal, where geographic information systems have contributed to bringing
      research and the field closer together.

PMID- 18047166
TI  - Introduction of an isolation policy in paediatric wards.
AB  - Where and how to care for children with infections, or those requiring
      protection, is a daily debate in many paediatric settings. The practice of
      placing patients into single rooms for infection control purposes is well
      documented but there is little guidance on when to remove patients from isolation
      rooms. Unless the appropriateness of isolation for each patient is evaluated
      daily, the availability of cubicles falls, resulting in potentially unnecessary
      transfers to other hospitals where such facilities are available. A new isolation
      policy was introduced to improve the availability of isolation rooms on
      paediatric wards in a large inner city teaching hospital with over 100 paediatric
      inpatient beds. A change management framework was used that included empowering
      organisational action and consolidating improvements. A number of strategies were
      introduced to prompt daily review of children in isolation, including clear
      criteria for isolation and nursing staff in the emergency department challenging
      the decision to admit a child into an isolation room. Introduction of the policy
      and subsequent audits have resulted in improved staff awareness, more effective
      use of isolation rooms and reduced transfers to other hospitals.

PMID- 18047167
TI  - Head injury.

PMID- 18047168
TI  - Supporting breastfeeding mothers in hospital: part 2b.
AB  - In this third article in the series, two further hypothetical scenarios are used
      to provide guidance on supporting breastfeeding mothers when the baby has a
      craniofacial anomaly or a cardiac defect. Successful breastfeeding in such
      circumstances has a positive effect on maternal confidence and attachment, and
      appears in itself to have healing potential. Unexpected benefits of breastfeeding
      critically ill babies include enhanced immunity and feeding tolerance in babies
      undergoing chemotherapy. A structured breastfeeding support service can assist
      staff in promoting successful breastfeeding in the paediatric environment.
      Expert, experiential knowledge of overcoming challenges in breastfeeding for
      mothers of critically ill babies can be applied in the absence of research
      evidence.

PMID- 18047169
TI  - Severe allergy: an audit and service review.
AB  - BACKGROUND: In 2002, a paediatric respiratory service in South Wales carried out
      a study to identify children in local schools who had a diagnosis of severe
      allergy, requiring them to carry an epipen. This investigation was carried out as
      a result of three schools seeking advice. Three children were identified as
      suffering from severe allergy; one child from each of the three schools. It was
      evident that sufficient education and support was not available for these
      children, their families and school staff regarding allergy management. This led
      to further investigation to see if there were others experiencing similar
      problems. METHOD: To identify school-aged children with a diagnosis of severe
      allergy, a survey took place of the three schools mentioned above plus a further
      111 schools. Sixteen additional children were noted to be carrying epipens in 16
      separate schools. An audit pro forma was devised and used to collect relevant
      data to establish previous allergy management and current allergy status. The 16
      children and their families were invited to an assessment clinic where they were
      interviewed by a respiratory nurse specialist. RESULTS: There were deficiencies
      in allergy management relating to: assessment, diagnosis, medication provision,
      education, support and ongoing follow up. These deficiencies highlighted the need
      for the development of a paediatric allergy service and a multi professional
      collaborative approach to care. CONCLUSION: The findings from the five phases of
      this study have influenced the development of an allergy clinic. This has led to
      collaborative working between healthcare professionals, school staff, children,
      and their families. The findings have promoted practice in terms of conducting
      thorough nursing and medical assessment, appropriate diagnosis, education and
      ongoing support for children and their families.

PMID- 18047170
TI  - Spiritual needs of children with complex healthcare needs in hospital.
AB  - AIMS: To explore the views of hospitalised school-aged children with complex
      healthcare needs related to spiritual care. This could help inform national
      policies and raise awareness of the impact that a stay in an acute paediatric
      hospital can have on the spiritual needs of some of the children who use the NHS.
      METHOD: Pictures used in previous (US) studies were used to facilitate story
      telling, enabling children to talk about concepts that may not have emerged
      through direct conversation. A convenience sample of five hospitalised children
      were presented with the pictures one at a time and asked open-ended questions
      about each picture. Data analysis involved identifying emerging themes from the
      transcriptions using a grounded theory approach. FINDINGS: The main themes to
      emerge from the interview data were: the role of the child's relationships with
      family, friends and healthcare professionals; the impact of the hospital
      environment on the child; coping with invasive procedures; belief--children's
      views about their health and belief system. CONCLUSION: There is a need for all
      healthcare professionals to recognise that children have spiritual needs that can
      include religious beliefs, and that it is part of their duty of care to attempt
      to identify and meet such needs.

PMID- 18047171
TI  - Modernising nursing careers: implications for children's nurses.
AB  - The future direction of pre-registration nursing education in the U.K. is once
      again under review with two consultation documents published by the Nursing and
      Midwifery Council (NMC). Pre-registration programmes need to prepare nurses who
      are able to provide holistic care to children, young people and families across
      all settings. In 2003 a position statement from the Royal College of Nursing
      proposed a model that encompassed: a foundation shared with other professionals
      involved in the care of children and young people, general nursing of children
      and young people, as well as theoretical and practical experience in public
      health, mental health and learning disability nursing of children and young
      people. This model is recommended as the way forward to ensure children's nursing
      is fit for the future

PMID- 18047172
TI  - Supporting children with Noonan syndrome.
AB  - Noonan syndrome, a genetic condition occurring in around 1 in 2,000 live births,
      was first described in 1968 by Dr Jacqueline Noonan, an American cardiologist,
      who noticed that patients attending her clinic often had similar features. After
      Down syndrome, it is the second most common syndrome associated with congenital
      heart defects but remains largely unknown outside of specialist areas. Three
      genetic mutations have been isolated as causes, although in around 35 per cent of
      cases the cause is, as yet, unknown. There is a lot of research into the genetic
      causes being done and there may be new discoveries in the near future

PMID- 18047173
TI  - Complex palliative care and transition: a case review.
AB  - This case study assesses the effect that health and social care had on the
      chronic life-limiting condition of a young man going through transition from
      children's to adult services. He was taken into foster care at 16 years old and
      placed with his maternal uncle and aunt. Relevant literature is introduced to
      consider the impact that placement had on the foster family and the young person
      as he was transitioned over a two-year period to adult services, not only in
      terms of their adaptations, but also on his health and prognosis. Close liaison
      between social services and hospital and community teams meant that medical and
      social outcomes were markedly improved for this young man.

PMID- 18047174
TI  - Top ten hot topics in parenteral science and technology.
AB  - Ten current "hot topics" in parenteral science and technology are reviewed to
      update the reader on current advances and challenges with each topic. Topics
      selected are formulation advances, packaging advances, extractables and
      leachables, analytical method advances for biopharmaceuticals, protein
      pharmaceutics, quality by design, manufacturing and equipment advances, aseptic
      processing advances, rapid microbial methods, and visual inspection of parenteral
      products.

PMID- 18047175
TI  - Preparation and physicochemical and preclinical evaluations of recrystallized
      celecoxib.
AB  - The aim of the present study is to increase the aqueous solubility of celecoxib
      by recrystallization from distilled water, Tween-80, and polyethylene glycol-400.
      The prepared crystals were evaluated for various physicochemical evaluations,
      dissolution rate, and in vivo performance like analgesic activity (by writhing
      and hot plate method) and pharmacokinetics in mice. The practical yield of the
      crystals ranged between 83 and 98%, and celecoxib content was more than 99%.
      Celecoxib showed an almost 5-fold increase in solubility when recrystallized in
      the presence of Tween-80 (2%). The dissolution rates of celecoxib from the co
      crystal forms were considerably higher than that of plain celecoxib. The infrared
      and differential scanning calorimetry studies indicated the absence of a well
      defined interaction between celecoxib and carriers. The differential scanning
      calorimetry and X-ray diffraction studies indicated the amorphization or partial
      amorphization of the drug. The scanning electron microscopy showed fluffy,
      porous, and fine particles in recrystallized celecoxib. The particle size of
      prepared co-crystals was considerably reduced in comparison with plain celecoxib.
      The crystals prepared with Tween-80 (2%) showed significantly higher analgesic
      activity than plain celecoxib. In pharmacokinetic study, the prepared crystals
      exhibited significantly high and rapid absorption along with improved
      bioavailability.

PMID- 18047177
TI  - Microbial diversity in pharmaceutical product recalls and environments.
AB  - Identification of microbial contaminants in product recalls and environmental
      samples provides important information on the possible contamination sources and
      distribution of microbial species in pharmaceutical environments. Analysis of FDA
      product recall data for 134 non-sterile pharmaceutical products from 1998 to
      September 2006 demonstrated that 48% of recalls were due to contamination by
      either Burkholderia cepacia, Pseudomonas spp., or Ralstonia picketti, while yeast
      and mold contamination were found in 23% of recalls. Gram-negative bacteria
      accounted for 60% of recalls, but only 4% were associated with Gram-positive
      bacteria. Of the 193 recalls of sterile products, 78% were due to the lack of
      sterility assurance and 7% for yeast and mold contamination. For sterile
      products, Gram-negative bacteria accounted for 6% of recalls, with only 1% due to
      Gram-positive bacteria. For non-sterile and sterile products, B. cepacia was the
      most frequently isolated microbial species with 22% and 2.5% of recalls,
      respectively. Based upon the review of the scientific literature, B. cepacia,
      Pseudomonas spp., or Ralstonia picketti may be associated with water
      contamination, while yeast and mold and Gram-positive bacteria may have indicated
      deficient environmental controls. The presence of unculturable microbial
      populations in pharmaceutical waters and clean rooms was reported, but no
      evidence has been published that product quality was negatively affected.

PMID- 18047176
TI  - Evolution of endotoxin contamination during production of a therapeutic serum.
AB  - A comparative bench-scale study of endotoxin contamination is presented for two
      common processes of immunoglobulin purification from equine plasma: ammonium
      sulphate fractionation of F(ab')2 fragments and caprylic acid precipitation of
      non-IgG proteins. To this end, both processes were carried out under normal
      sterile conditions, using sanitized material and equipment and optimal water
      quality in a clean but open environment. Stream samples, taken at different
      stages from each process, were analyzed for endotoxin content by the Limulus
      Amebocyte Lysate (LAL) test. It was found that exogenous contamination
      preferentially came from endotoxins already present in reagents and/or raw
      materials, whereas contamination from the environment was minimal. Endogenous
      endotoxin accumulation, concomitant with the concentration of proteins during
      processing, was found to be an important factor. With classic technology, blood
      extraction and sterilizing filtration are critical points for both processes. It
      is concluded that sterility is not a sufficient condition to obtain an endotoxin
      free product. Only with proper sanitization of material, and by applying the
      caprylic acid purification process with a starting plasma below 4-5 EU/mL, would
      it be possible to achieve a final product within the norm.

PMID- 18047178
TI  - In vivo and in vitro evaluation of a solid dispersion system of gliclazide:PEG
      6000.
AB  - OBJECTIVE: Gliclazide is a potent antidiabetic agent because of its capability to
      decrease blood glucose level via stimulating endogenous insulin secretion from
      beta-pancreas cells. Gliclazide is insoluble in water and has low dissolution
      rate. In this study, polyethylene glycol (PEG) 6000 was used as a matrix to
      disperse gliclazide in the solid state, and the pharmacokinetic profile of this
      solid dispersion was studied in rats. DESIGN: The solid dispersion of
      Gliclazide:PEG 6000 (1:4) was prepared by solvent evaporation method. MAIN
      OUTCOME MEASURES: Samples characterization included differential scanning
      calorimetry (DSC), infrared spectroscopy (IR), X-ray diffraction (XRD), and
      solubility and dissolution test. In vivo study was carried out in healthy rats,
      randomly. After a single dose of oral administration, blood samples were
      collected pre-dose (15 min before) and 1, 2, 3, 4, 5, 6, 8, 10, and 12 h post
      dose. Plasma concentration of gliclazide was determined by high pressure liquid
      chromatography method using C-18 column, with mobile phase KH2PO4 (pH 4.6)
      acetonitril (40:60 v/v) and UV detection at 229 nm. RESULTS: Results showed that
      there were no differences in DSC, IR spectroscopy, XRD, and dissolution test
      between the solid dispersion and physical mixture. In vivo data showed that the
      Tmax of gliclazide in solid dispersion and physical mixture was significantly
      decreased, while the Cmax, AUC(0-12), and AUC(0-infinity) were significantly
      increased compared to gliclazide alone. These results indicate that the rapid
      Tmax was due to rapid absorption of gliclazid across the GI tract membrane.
      Increased Cmax, AUC(0-12), and AUC(0-infinity) indicate a better absorption of
      gliclazide in solid dispersion and physical mixture than of gliclazide alone.
      CONCLUSION: Increased in gliclazide dissolution in the presence of PEG 6000 was
      followed by improved in vivo data.

PMID- 18047179
TI  - Rapid diagnostic method for quantitative testing of <100 microbes in water.
AB  - A robust, real-time polymerase chain reaction (RT-PCR) system to universally
      detect microbes at a limit of 10 to 50 colony-forming units within 5-6 h was
      developed. Pre-treatment of RT-PCR master mixes with ethidiumbromide monoacide
      (EMA) facilitates the development of an RT-PCR assay with appropriate
      sensitivity, reproducibility, and recovery.The system is useful to replace
      conventional microbial plating techniques for the analysis of microbial
      contamination in liquids like water. This was statistically confirmed for eight
      different bacteria and two different fungi species. Finally a complete procedure
      including microbial lysis, DNA extraction, EMA treatment, and RT-PCR was
      developed and evaluated for three different bacteria and two fungi species.

PMID- 18047180
TI  - Reduced admissions for acute myocardial infarction associated with a public
      smoking ban: matched controlled study.
AB  - There has been no research linking implementation of a public smoking ban and
      reduced incidence of acute myocardial infarction (AMI) among nonsmoking patients.
      An ex post facto matched control group study was conducted to determine whether
      there was a change in hospital admissions for AMI among nonsmoking patients after
      a public smoking ban was implemented in Monroe County compared with Delaware
      County, Indiana without such a ban. Poisson analysis was conducted for 44 months
      of hospital admissions. A significant drop occurred in the number of admissions
      among nonsmoking patients in Monroe County after the ban whereas a nonsignificant
      decrease in the number of admissions occurred in Delaware County. The changes in
      the number of smoking-patient admissions before and after the ban were not
      significant.

PMID- 18047181
TI  - A community prevention intervention to reduce youth from inhaling and ingesting
      harmful legal products.
AB  - Youth use of harmful legal products, including inhaling or ingesting everyday
      household products, prescription drugs, and over-the-counter drugs, constitutes a
      growing health problem for American society. As such, a single targeted approach
      to preventing such a drug problem in a community is unlikely to be sufficient to
      reduce use and abuse at the youth population level. Therefore, the primary focus
      of this article is on an innovative, comprehensive, community-based prevention
      intervention. The intervention described here is based upon prior research that
      has a potential of preventing youth use of alcohol and other legal products. It
      builds upon three evidence-based prevention interventions from the substance
      abuse field: community mobilization, environmental strategies, and school-based
      prevention education intervention. The results of a feasibility project are
      presented and the description of a planned efficacy trial is discussed.

PMID- 18047182
TI  - Protective and risk influences of drug use among a multiethnic sample of
      adolescent boys.
AB  - A measurement model was analyzed to demonstrate a differential distribution and
      cumulative exposure to psychosocial risk and protective influences of adolescent
      drug use among ethnically-diverse adolescent samples. The sample included U.S.
      born (US) Latino (N = 837), foreign-born (FB) Latino (N = 447), White (N = 632),
      and African American (N = 618) adolescent boys. Psychological Distress, Peer Drug
      Use, and Adolescent Drug Use were significantly positively correlated with Peer
      Drug Use and Adolescent Drug Use. In contrast, Family, School, law abidance, and
      guilt were significantly negatively correlated with Peer Drug Use and Adolescent
      Drug Use. Multiple group analyses indicated significant similarities and
      differences among US and FB Latinos, and Whites. Implications for early
      prevention, multi-level interventions, and suggestions for future research are
      discussed.

PMID- 18047183
TI  - Alcohol involvement and the Five-Factor model of personality: a meta-analysis.
AB  - The purpose of this meta-analysis was to quantify the relationship between the
      Five-Factor Model of personality and alcohol involvement and to identify
      moderators of the relationship. The meta-analysis included 20 studies, 119 effect
      sizes, and 7,886 participants. Possible moderators examined included: five-factor
      rating type (self vs. other); study time-frame (cross sectional vs.
      longitudinal); sample type (treatment vs. non-treatment); type of alcohol
      involvement measure used; gender of the participants; and age of the
      participants. The meta-analysis showed alcohol involvement was associated with
      low conscientiousness, low agreeableness, and high neuroticism, a personality
      profile that: a) fits on the low end of a superordinate personality dimension
      that has been called self-control; and b) makes treatment difficult. Several
      significant moderators of effect size were found, including the following:
      studies of individuals in treatment for alcohol problems showed a more negative
      pattern of personality traits than did other studies; cross-sectional studies,
      but not longitudinal studies, showed a significant effect for agreeableness,
      perhaps suggesting that low agreeableness may have a different causal link to
      alcohol involvement from the other factors; mixed-sex samples tended to have
      lower effect sizes than single-sex samples, suggesting that mixing sexes in data
      analysis may obscure effects.

PMID- 18047184
TI  - Improving the sensitivity of needs assessment for substance abuse prevention
      planning: the measurement of differential severity of consequences for individual
      substance types.
AB  - There is an absence of systematic, comparative research examining the negative
      consequences that are experienced as a result of using specific substances.
      Further, techniques typically used for needs assessment (i.e., prevalence
      proportions) do not take into account the probability of experiencing a negative
      consequence as a result of using specific substances. An approximated severity
      index is proposed that: a) takes into account the probability of experiencing
      negative consequences as a result of using specific substances; and b) is
      comparable across substances. Data from the NSDUH and the ADSS are used to
      demonstrate these techniques. The findings suggest that substances typically
      considered priorities based on prevalence proportions are not the same substances
      that have a high probability of causing negative consequences. The policy
      implications of these findings are discussed.

PMID- 18047185
TI  - A preliminary evaluation of the effects of a science education curriculum on
      changes in knowledge of drugs in youth.
AB  - Drug and alcohol use among youth remains at pervasively high levels, but students
      are receiving less school-based prevention. Infusing health information into core
      curricula may be a valuable prevention approach. Therefore, behavior change
      theory was used to develop a science education curriculum on drugs for fourth-
      and fifth-grade students, which was then evaluated using a pretest/posttest quasi
      experimental design. Exposure to the curriculum was associated with a change in
      knowledge; other characteristics like grade level also played a role. More
      positive attitudes toward science at pretest predicted greater knowledge change,
      and students who knew less at the start showed a greater change in knowledge.
      Results of this evaluation may support the efficacy of the curriculum and the
      utility of combining behavior change theory with educational approaches.

PMID- 18047186
TI  - The moderating effects of culture on peer deviance and alcohol use among high
      risk African-American Adolescents.
AB  - African-American adolescents have lower rates of alcohol consumption than White
      youth. However, African-American youth suffer disproportionately more adverse
      social, mental, and physical health outcomes related to alcohol use. Affiliating
      with negative peers is a risk factor for alcohol initiation and consumption.
      Cultural variables have shown moderating effects against other risk factors for
      African-American youth and therefore were the focus of this study. Specifically,
      we tested whether three culturally-relevant variables, Africentric beliefs,
      religiosity, and ethnic identity were promotive or protective for alcohol
      initiation and use within the context of negative peer affiliations. The sample
      consisted of 114 at-risk African-American adolescents whose ages ranged from 13
      to 20. Participants were administered a questionnaire with measures of alcohol
      initiation and use, peer risk behaviors, ethnic identity, Africentric beliefs,
      religiosity, and demographic items. Peer risk behaviors accounted for significant
      percentages of the variance in age of alcohol initiation, lifetime use, and
      current and heavy alcohol use after adjusting for age and gender. Cultural
      variables showed both promotive and protective effects. Africentric beliefs were
      promotive of delayed alcohol initiation, whereas both Africentrism and
      religiosity moderated peer risk behaviors effect on alcohol initiation.
      Africentric beliefs were also inversely related to lifetime alcohol use revealing
      a promotive effect. Moreover, there were significant protective effects of ethnic
      identity and religiosity on heavy alcohol consumption. One implication of these
      findings is that prevention programs that infuse cultural values and practices
      such as Africentrism, ethnic identity, and religiosity may delay alcohol
      initiation and reduce use especially for youth with high risk peers.

PMID- 18047187
TI  - Ultrastructural comparison of external morphology of immature stages of Lutzomyia
      (Nyssomyia) intermedia and Lutzomyia (Nyssomyia) whitmani (Diptera: Psychodidae),
      vectors of cutaneous leishmaniasis, by scanning electron microscopy.
AB  - Lutzomyia (Nyssomyia) intermedia (Lutz & Neiva 1912) and Lutzomyia (Nyssomyia)
      whitmani (Antunes & Coutinho 1939) (Diptera: Psychodidae) are vectors of American
      cutaneous leishmaniasis in several endemic regions of Brazil. We analyzed the
      external morphological aspects of the immature stages of these two vectors by
      using scanning electron microscopy. In general, the larval stages of the two
      species are morphologically similar, although some differences were noted.
      Detailed examination of the eggs of both species revealed similar exchorionic
      ornamentations of unconnected parallel ridges. The larval head capsules are well
      defined, heavily sclerotized, and bear prominent chewing mouthparts. The
      abdominal segments are easily recognized by the presence of prolegs on their
      ventral surfaces. The morphology of the anal lobe on the terminal abdominal
      segment differs between the two species. We found the following three types of
      sensillae inserted on the antennae: (1) clavate basiconic; (2) small, blunt
      coeloconic; and (3) multipourous clavate coleoconic. In addition; five subtypes
      of trichoid sensillae were found on the larval body: (1) long, (2) short, (3)
      curved long, (4) brush-like, and (5) weakly brush-like. The caudal filaments
      located on the last abdominal segment were recognized as long trichoid sensillae.
      We observed pores on the surface of the clavate coelonic sensillae and on the
      caudal filaments that presumably function as chemoreceptors. The larvae of the
      two species show similarities in the lobular-form antennae of L1 larvae, which
      changes to digitiform in second instar (L2), L3, and L4. This study demonstrated
      that the external surface of the eggs and larvae of Lu. intermedia and Lu.
      whitmani are morphologically similar, but they can be distinguished by details in
      the microanatomy observed by scanning electron microscopy.

PMID- 18047188
TI  - Observations and larval descriptions of fleas (Siphonaptera: Ceratophyllidae,
      Ctenophthalmidae, Ishnopsyllidae) of the southern flying squirrel, little brown
      bat, and Brazilian free-tailed bat (Mammalia: Rodentia, Chiroptera).
AB  - Larvae of the four fleas infesting nests of the southern flying squirrel,
      Glaucomys volans colans (L.) [Conorhinopsylla stanfordi Stewart, Epitedia faceta
      (Rothschild), Opisodasys pseudarctomys (Baker), and Orchopeas howardi (Baker)],
      and of the bat fleas Myodopsylla insignis (Rothschild) and Sternopsylla distincta
      texana (C. Fox), associated with the bats Myotis lcifuigus (Le Conte) and
      Tadarida brasiliensis (I. Geof. St. Hilaire), respectively, are described. C.
      stanfordi has the second posterior-row seta on abdominal segments 1-5 at most one
      fourth the length of the first and third setae, but it is unique among the
      Leptopsyllini with five short setae in abdominal segment 9 anterior row. E.
      faceta has the straight line of anterior-row setae 2-5 on abdominal segment 1,
      which is diagnostic for Phalacropsyllini. O. howardi and O. pseudarctomys have
      three anterior-row setae on the anal comb, three ventrolateral setae on the anal
      segment (abdominal segment 10), and a narrow mandible with five or more teeth as
      other Ceratopyllinae, but O. pseudarctomys is distinguishable from O. howardi
      because the first setae on the posterior row of the head is long (greater than
      one half the length of the third posterior-row setae), the ventral setae on
      abdominal segment 7 are different sizes, and the third anterior-row setae on
      abdominal segment 8 does not extend past the spiracle posterior to it. Bat flea
      larvae have six posterior-row setae on abdominal segments 1-9 with the anal comb
      anterior row with two or more setae; M. insignis has eight mandible teeth and S.
      distincta texana three to four.

PMID- 18047189
TI  - Estimating dispersal and survival of Anopheles gambiae and Anopheles funestus
      along the Kenyan coast by using mark-release-recapture methods.
AB  - Mark-release-recapture (MRR) experiments were conducted with emerging Anopheles
      gambiae s.l. and Anophelesfunestus Giles at Jaribuni and Mtepeni in Kilifi, along
      the Kenyan Coast. Of 739 and 1246 Anopheles released at Jaribuni and Mtepeni,
      24.6 and 4.33% were recaptured, respectively. The daily survival probability was
      0.96 for An. funestus and 0.95 for An. gambiae in Jaribuni and 0.83 and 0.95,
      respectively, in Mtepeni. The maximum flight distance recorded was 661 m. The
      high survival probability of An. gambiae and An. funestus estimated accounts for
      the continuous transmission of malaria along the Kenyan coast. This study also
      shows that the release of young, emergent female Anopheles improves the recapture
      rates and may be a better approach to MRR studies.

PMID- 18047190
TI  - Three calibration factors, applied to a rapid sweeping method, can accurately
      estimate Aedes aegypti (Diptera: Culicidae) pupal numbers in large water-storage
      containers at all temperatures at which dengue virus transmission occurs.
AB  - The ability of a simple sweeping method, coupled to calibration factors, to
      accurately estimate the total numbers of Aedes aegypti (L.) (Diptera: Culicidae)
      pupae in water-storage containers (20-6412-liter capacities at different water
      levels) throughout their main dengue virus transmission temperature range was
      evaluated. Using this method, one set of three calibration factors were derived
      that could accurately estimate the total Ae. aegypti pupae in their principal
      breeding sites, large water-storage containers, found throughout the world. No
      significant differences were obtained using the method at different altitudes (14
      1630 m above sea level) that included the range of temperatures (20-30 degrees C)
      at which dengue virus transmission occurs in the world. In addition, no
      significant differences were found in the results obtained between and within the
      10 different teams that applied this method; therefore, this method was extremely
      robust. One person could estimate the Ae. aegypti pupae in each of the large
      water-storage containers in only 5 min by using this method, compared with two
      people requiring between 45 and 90 min to collect and count the total pupae
      population in each of them. Because the method was both rapid to perform and did
      not disturb the sediment layers in these domestic water-storage containers, it
      was more acceptable by the residents, and, therefore, ideally suited for routine
      surveillance purposes and to assess the efficacy of Ae. aegypti control programs
      in dengue virus-endemic areas throughout the world.

PMID- 18047191
TI  - Standardizing container classification for immature Aedes aegypti surveillance in
      Kamphaeng Phet, Thailand.
AB  - For the development of community-based vector control programs for dengue
      prevention, one of the key components is to formulate an adequate classification
      scheme for the different containers in which immature Aedes mosquitoes develop.
      Such a standardized scheme would permit more efficient targeting of efforts and
      resources in the most productive way possible. Based on field data from Kamphaeng
      Phet, Thailand, we developed a classification method that consists of the shape
      (S), use (U), and material (M) of the container (SUM-method). We determined that
      by targeting the four container classes that held the most Ae. aegypti pupae,
      adult mosquito production could theoretically be reduced by 70%. The
      classification method may be equally suitable for similar studies elsewhere in
      the world. Main advantages of the classification scheme are that categorization
      of containers does not need to be done a priori, that there is no "miscellaneous"
      class, and that different immature control strategies can be easily and
      prospectively tested with a local database. We expect that the classification
      strategy will 1) facilitate comparison of results among different ecological and
      geographic settings and 2) simplify communication among vector control personnel
      and affected communities.

PMID- 18047192
TI  - Establishment and abundance of a recently introduced mosquito species
      Ochlerotatus japonicus (Diptera: Culicidae) in the Southern Appalachians, USA.
AB  - Ochlerotatus (Finlaya) japonicus japonicus (Theobald; =Aedes japonicus; see
      Reinert 2000) (Diptera: Culicidae), is an introduced Asian mosquito species first
      detected in the northeastern United States in 1998. Since its initial discovery,
      this species has spread to many neighboring states and Canada. It was first
      identified in North Carolina, South Carolina, and Georgia in 2003. Larval surveys
      were conducted during 2005 and 2006 in the Southern Appalachians, U.S.A., on a
      variety of natural and artificial containers to determine extent of Oc.japonicus
      establishment and larval habitat requirements. Detritus amounts were measured in
      each container habitat, and co-occurring larval mosquito species were examined as
      indicators of potential interspecific competition. Data reveal that Oc. japonicus
      was the most abundant container-inhabiting mosquito species in this survey. It
      exhibits flexibility in its use of container oviposition habitats, it can persist
      in a wide range of conditions, and it co-occurs with a wide range of larval
      mosquito species. Its rapid and successful establishment warrants continued
      monitoring, because its potential role as a nuisance species or arbovirus vector
      remains unknown.

PMID- 18047193
TI  - Ectoparasitic assemblages on mormoopid bats (Chiroptera: Mormoopidae) from Puerto
      Rico.
AB  - We performed the first quantitative survey of ectoparasitic assemblages on three
      species of mormoopid bats living on the Caribbean island of Puerto Rico: Mormoops
      blainvillii Leach (n=40), Pteronotus quadridens Gundlach (n=40), and Pteronotus
      parnellii Gray (n=9). We examined bats for parasites primarily on 8-10 May and 24
      27 July 2002 at Culebrones Cave, near Arecibo, Puerto Rico. Only 50% of M.
      blainvillii were infested with at least one parasite, compared with 85-100% for
      Pteronotus; infested individuals of both species of Pteronotus also harbored a
      greater number of parasites than did M. blainvillii. The assemblage on M.
      blainvillii was less diverse than in the other species and more dominated by a
      single group of parasites, the chiggers. Chirodiscid ear mites and spinturnicid
      wing mites were common on both species of Pteronotus but absent from M.
      blainvillii. All P. parnellii harbored streblid flies, but none typically was
      found on P. quadridens or M. blainvillii. Adult female M. blainvillii and P.
      quadridens sheltered a greater number of ectoparasites than did males. All host
      parasite combinations represented new associations for Puerto Rico.

PMID- 18047194
TI  - Seasonal abundance, parity, and survival of adult Culicoides sonorensis (Diptera:
      Ceratopogonidae) in southern Alberta, Canada.
AB  - Culicoides sonorensis (Wirth & Jones) (Diptera: Ceratopogonidae) adults were
      active from May through October during 2002-2006 in southern Alberta, Canada.
      Adults were first captured in May, and populations peaked in early June, late
      July, and late August. The first population peak occurred when mean weekly
      temperatures exceeded 16 degrees C, resulting in a variable amount of time for
      spring emergence. This asynchrony in spring emergence accounted for much of the
      annual variation in timing of subsequent population peaks. Peaks were separated
      by an average of 6-7 wk. C. sonorensis seems to have one overwintering generation
      and two generations during the summer. Abundance was correlated among sites
      located up to 90 km apart. Abundance at a rangeland site increased more rapidly
      with mean weekly temperatures than at feedlot sites. The proportion female ranged
      from 0.68 to 0.83 but showed no consistent differences between rangeland and
      feedlot sites. The proportion female declined with distance from a developmental
      area at the rangeland site. Proportion parous was similar among rangeland and
      feedlot sites, and it also declined with distance from a developmental area at
      the rangeland site. The proportion parous increased early in the season,
      fluctuated throughout the mid-season, and increased with cooler temperatures in
      the fall. The proportion parous tended to increase when temperatures decreased.
      Estimates of adult daily survival were generally >0.8. Survival declined with
      temperature, was lowest in midsummer, and increased during the fall.

PMID- 18047196
TI  - Comparison of larval foraging behavior of Aedes albopictus and Aedes japonicus
      (Diptera: Culicidae).
AB  - Aedes albopictus (Skuse) (Diptera: Culicidae) invaded the United States in 1985
      and spread rapidly across eastern North America, whereas Aedes japonicus
      (Theobald) invaded and became established in the United States more recently
      (1998). The two species may co-occur in container habitats, and they are of
      potential public health concern as arbovirus vectors. To evaluate ecological
      differences between Ae. albopictus and Ae.japonicus, we compared larval foraging
      behavior of these two species. Based on results from a previous competition
      experiment, we predicted that Ae. albopictus would be a more active forager than
      Ae. japonicus. However, Ae. japonicus exhibited greater foraging activity than
      Ae. albopictus in four of six food environments, including a "no food" control
      treatment. Our results, therefore, suggest that more active foraging does not
      connote superior competitive ability, and competitive interactions between these
      species may be mediated by factors other than feeding behavior.

PMID- 18047195
TI  - Attractiveness of MM-X traps baited with human or synthetic odor to mosquitoes
      (Diptera: Culicidae) in The Gambia.
AB  - Chemical cues play an important role in the host-seeking behavior of blood
      feeding mosquitoes (Diptera: Culicidae). A field study was carried out in The
      Gambia to investigate the effects of human odor or synthetic odor blends on the
      attraction of mosquitoes. MM-X traps baited with 16 odor blends to which carbon
      dioxide (CO2) was added were tested in four sets of experiments. In a second
      series of experiments, MM-X traps with 14 odor blends without CO2 were tested. A
      blend of ammonia and L-lactic acid with or without CO2 was used as control odor
      in series 1 and 2, respectively. Centers for Disease Control and Prevention (CDC)
      traps were placed in a traditional house and an experimental house to monitor
      mosquito densities during the experiments. The MM-X traps caught a total number
      of 196,756 mosquitoes, with the most abundant species belonging to the genera
      Mansonia (70.6%), Anopheles (17.5%), and Culex (11.5%). The most abundant
      mosquito species caught by the CDC traps (56,290 in total) belonged to the genera
      Mansonia (59.4%), Anopheles (16.0% An. gambiae s.l. Giles, and 11.3% An. ziemanni
      Grunberg), and Culex (11.6%). MM-X traps baited with synthetic blends were in
      many cases more attractive than MM-X traps baited with human odors. Addition of
      CO2 to synthetic odors substantially increased the catch of all mosquito species
      in the MM-X traps. A blend of ammonia + L-lactic acid + CO, + 3-methylbutanoic
      acid was the most attractive odor for most mosquito species. The candidate odor
      blend shows the potential to enhance trap collections so that traps will provide
      better surveillance and possible control.

PMID- 18047197
TI  - Anopheles funestus (Diptera: Culicidae) in a humid savannah area of western
      Burkina Faso: bionomics, insecticide resistance status, and role in malaria
      transmission.
AB  - An entomological survey was carried out in three humid savannah sites of western
      Burkina Faso (Bama, Lena, and Soumousso) to (1) update the taxonomy of the
      Anopheles funestus Giles group, (2) examine the role of each species in malaria
      transmission, (3) characterize the insecticide resistance status of this malaria
      vector, and (4) determine the distribution of An. funestus chromosomal forms in
      these areas. Polymerase chain reaction identification of the members showed the
      occurrence of An. leesoni Evans in Lena and An. rivulorum-like in Soumousso in
      addition to An. funestus s.s. Malaria transmission was ensured mainly by An.
      funestus s.s. both in Soumousso and Lena and by An. gambiae s.s. Giles in Bama,
      the rice-growing area. The insecticide resistance status performed only on An.
      funestus indicated that this mosquito was susceptible to pyrethroids irrespective
      of the study area, but it was resistant to dieldrin. Furthermore, the occurrence
      of the two chromosomal forms of An. funestus, namely, Kiribina and Folonzo,
      seemed to follow ecological setups where Kiribina predominated in the irrigated
      area and Folonzo was more frequent in classic savannah. This study revealed that
      the problematic of An. funestus taxonomy was closer to that of An. gambiae
      requiring more structured studies to understand its genetic ecology.

PMID- 18047198
TI  - Phylogeography of stable fly (Diptera: Muscidae) estimated by diversity at
      ribosomal 16S and cytochrome oxidase I mitochondrial genes.
AB  - The blood-feeding cosmopolitan stable fly, Stomoxys calcitrans L. (Diptera:
      Muscidae), is thought to disperse rapidly and widely, and earlier studies of
      allozyme variation were consistent with high vagility in this species. The
      geographic origins of New World populations are unknown. Diversity at
      mitochondrial loci r16S and cytochrome oxidase I was examined in 277 stable flies
      from 11 countries, including five zoogeographical regions. Of 809 nucleotides,
      174 were polymorphic and 133 were parsimony informative. Seventy-six haplotypes
      were found in frequencies consistent with the Wright-Fisher infinite allele
      model. None were shared among four or more zoogeographical regions. The null
      hypothesis of mutation neutrality was not rejected, thereby validating the
      observed distribution. Fifty-nine haplotypes were singular, eight were private
      and confined to the Old World, and three of 76 haplotypes were shared between the
      Old and New World. Only 19 haplotypes were found in the New World, 14 of which
      were singletons. Haplotype and nucleotide diversities were heterogeneous among
      countries and regions. The most diversity was observed in sub-Saharan Africa.
      Regional differentiation indices were C(RT) = 0.26 and N(RT) = 0.31, indicating
      populations were highly structured macrogeographically. Palearctic and New World
      flies were the least differentiated from each other. There were strong genetic
      similarities among populations in the Nearctic, Neotropical, and Palearctic
      regions, and it is most likely that New World populations were derived from the
      Palearctic after 1492 CE, in the colonial era.

PMID- 18047199
TI  - Body lice and head lice (Anoplura: Pediculidae) have the smallest genomes of any
      hemimetabolous insect reported to date.
AB  - The human body louse, Pediculus humanus humanus L. (Anoplura: Pediculidae), is a
      vector of several diseases, including louse-borne epidemic typhus, relapsing
      fever, and trench fever, whereas the head louse, Pediculus humanus capitis De
      Geer (Anoplura: Pediculidae), is more a pest of social concern. Sequencing of the
      body louse genome has recently been proposed and undertaken by National Human
      Genome Research Institute. One of the first steps in understanding an organism's
      genome is to determine its genome size. Here, using flow cytometry
      determinations, we present evidence that body louse genome size is 104.7 +/- 1.4
      Mb for females and 108.3 +/- 1.1 Mb for males. Our results suggest that head lice
      also have a small genome size, of similar size to the body louse. Thus, Pediculus
      lice have one of the smallest genome sizes known in insects, suggesting it may be
      a suitable choice as a minimal hemimetabolous genome.

PMID- 18047200
TI  - R86Q, a mutation in BmAChE3 yielding a Rhipicephalus microplus organophosphate
      insensitive acetylcholinesterase.
AB  - Mutations were identified in the cDNA sequence encoding the acetylcholinesterase
      BmAChE3 in strains of Rhipicephalus (Boophilus) microplus (Canestrini) resistant
      or susceptible to organophosphate (OP) acaricide. The mutation that occurred most
      frequently in the OP-resistant San Roman strain resulted in a substitution of
      glutamine (Q) for arginine (R) at position 86 in BmAChE3 (position 66 in mature
      BmAChE). Clones containing the mutant and wild-type cDNA sequences were expressed
      in the baculovirus system. Enzyme kinetics of recombinant BmAChE3 containing or
      lacking the R86Q mutation demonstrated that the R86Q mutation increased substrate
      affinity and conferred insensitivity to paraoxon inhibition. This is the first
      demonstration of a mutation in a gene encoding an ixodid acetylcholinesterase
      resulting in OP insensitivity. A restriction fragment length polymorphism assay
      was developed and used to diagnose the frequency of the R86Q mutation in BmAChE3
      genomic DNA from seven laboratory-colonized strains. Use of the R86Q diagnostic
      assay detected an increased frequency of the R86Q mutation in OP-resistant tick
      strains compared with that of OP-susceptible strains; however, the R86Q mutation
      was also present in OP-susceptible strains at unexpectedly high frequency.
      Because the R86Q mutation generates an OP-resistant enzyme in vitro and it is
      present at an elevated frequency in laboratory strains selected for OP
      resistance, we conclude that the data are consistent with a potential role for
      BmAChE3 in development of OP resistance; however, because the R86Q mutation has a
      high frequency in susceptible strains, the R86Q mutation alone is insufficient to
      generate the OP-resistant phenotype at the organismal level. There are likely to
      be additional mutations in BmAChE3, mutations in additional acetylcholinesterase
      genes, or additional resistance mechanisms (e.g., oxidative metabolism) that
      contribute to expression of the OP-resistant phenotype.

PMID- 18047201
TI  - Molecular identification of Western European species of obsoletus complex
      (Diptera: Ceratopogonidae) by an internal transcribed spacer-1 rDNA multiplex
      polymerase chain reaction assay.
AB  - In southern Europe, orbiviral diseases such as bluetongue (BT) have been assumed
      to have been largely transmitted by the classical Afro-Asian vector Culicoides
      imicola Kieffer (Diptera: Ceratopogonidae). Recent outbreaks have occurred in
      regions where C. imicola is normally absent, supporting the theory that other
      species belonging to the Obsoletus or Pulicaris complexes may play a role in BT
      virus transmission. Investigations of the ecology of the species within the
      former group are hampered by females of member species being extremely difficult
      to separate by classical morphology. To allow straightforward separation of these
      species in France, a multiplex polymerase chain reaction-based on internal
      transcribed spacer (ITS)-1 rDNA was developed to distinguish between Culicoides
      chiopterus Meigen, Culicoides dewulfi Goetghebuer, Culicoides montanus
      Shakirjanova, Culicoides obsoletus Meigen, and Culicoides scoticus Downes &
      Kettle. This tool will be useful in defining both the vector role and larval
      biotopes of these species in Europe.

PMID- 18047202
TI  - Laboratory and field evaluation of the impact of exercise on the performance of
      regular and polymer-based deet repellents.
AB  - Studies were done in Manitoba, Canada, to evaluate the impact of exercise on
      repellent performance against mosquitoes. Two products containing the active
      ingredient N,N-diethyl-3-methylbenzamide (deet) were tested; one product was a
      polymer-based cream (3M Ultrathon Insect Repellent) and the other product was an
      alcohol-based pump spray formulation (Muskol Insect Repellent). Assessments were
      done in the laboratory using Aedes aegypti (L.) and in the field with naturally
      occurring populations of mosquitoes. Repellent was applied to the forearms
      (laboratory) or a lower leg (field) of test subjects at 1.5 g of test product per
      600 cm2 surface area (0.75 or 0.83 mg deet/cm2). For a given test day, subjects
      exercised or did not. Exposure to mosquito attack was for 1 min at 30-min
      intervals in laboratory procedures, and it was continuous in field tests.
      Performance was measured as complete protection time (CPT). Moderate levels of
      physical activity resulted in a >40% decline in mean CPT, from 468 to 267 min in
      the laboratory experiments and from 359 to 203 min in field tests. Repellent
      product did not affect the magnitude of the decline. Mean biting pressure during
      field trials was 21.3 bites per min, and mosquito collections were made up
      primarily of Ochlerotatus sticticus (Meigen) and Aedes vexans (Meigen).

PMID- 18047203
TI  - Behavioral responses of malaria vectors, Anopheles minimus complex, to three
      classes of agrochemicals in Thailand.
AB  - Behavioral responses of two wild-caught populations of Anopheles minimus complex,
      species A and C, exposed to operational field doses of three commonly used
      agricultural insecticides, carbaryl (carbamate), malathion (organophosphate) and
      cypermethrin (pyrethroid), were characterized using an excito-repellency test
      system. Test populations were collected from different localities in Kanchanaburi
      Province, western Thailand. Both populations showed strong irritancy by quickly
      escaping test chambers after direct contact with individual surfaces treated with
      each insecticide compared with match-paired untreated controls. Noncontact
      repellency response to cypermethrin and carbaryl was significantly pronounced in
      both A and C populations, but comparatively weak when exposed to malathion.
      Noncontact repellency produced much weaker escape response in both populations,
      but in some species-chemical combinations, it remained significant compared with
      controls. We conclude that contact irritancy is a major behavioral response of
      both A and C when exposed directly to any of the three compounds, whereas only
      cypermethrin produced a significant repellency response in species A.

PMID- 18047204
TI  - Microsporidiosis (Microsporidia: Culicosporidae) alters blood-feeding responses
      and DEET repellency in Aedes aegypti (Diptera: Culicidae).
AB  - Infection of Aedes aegypti (L.) (Diptera: Culicidae) with Edhazardia aedis
      (Microsporidia: Culicosporidae) reduced mean human host attraction and
      landing/probing rates in female mosquitoes by 53 and 62%, respectively, compared
      with rates in microsporidia-free females. Infection with E. aedis reduced the
      average weight of unfed female mosquitoes by 4%, caused them to imbibe 23% less
      blood, and to lay 30% fewer eggs than healthy females. In contrast, E. aedis
      infected mosquitoes required 20% more time (>1 h) than healthy females to bite
      skin treated with 15% DEET. Statistically significant morbidity in E. aedis
      infected females was indicated by reductions in host attraction and
      landing/probing responses, the mass of unfed and blood-engorged females, and
      fecundity, and by increased DEET repellency.

PMID- 18047205
TI  - Comparative studies on effects of three chitin synthesis inhibitors on common
      malaria mosquito (Diptera: Culicidae).
AB  - Toxicities of three chitin synthesis inhibitors (diflubenzuron, nikkomycin Z and
      polyoxin D) were evaluated using second instars of the common malaria mosquito,
      Anopheles quadrimaculatus Say (Diptera: Culicidae). Neither nikkomycin Z nor
      polyoxin D at 50 microg/liter caused significant larval mortality, although they
      reduced the body weight of the survivors by 20.5 and 33.8%, respectively, in 48
      h. In contrast, exposures of the larvae to diflubenzuron at 12.5 microg/liter for
      48 h resulted in 86.7% larval mortality and reduced the body weight of the
      survivors by 29.1%. Exposure of the pupae (<12 h old) to diflubenzuron at 100
      microg/liter for 48 h caused 18.9% pupal mortality and consequently reduced the
      adult emergence by 24.7% from the surviving pupae. Furthermore, exposure of third
      instars to diflubenzuron at 4, 20, 100, and 500 microg/liter for 24 h resulted in
      the reduction of larval chitin contents by 4.25, 33.2, 35.2, and 57.7%,
      respectively. Such an effect seemed to be associated with only cuticular chitin
      synthesis because the same exposures did not significantly affect chitin contents
      in the guts. Our results indicated that diflubenzuron was highly toxic to second
      instars by not only causing high larval mortality but also by affecting their
      growth. Diflubenzuron was also fairly toxic to pupae by not only causing pupal
      mortality but also affecting the adult emergence. Our results suggest that
      diflubenzuron might affect only chitin synthesis in the cuticle but not in the
      peritrophic matrix, which is probably due to diflubenzuron's direct contact to
      mosquito larvae in water, slow distribution in insect body, rapid degradation in
      the insect gut, or a combination.

PMID- 18047206
TI  - In vivo evidence that Sarcoptes scabiei (Acari: Sarcoptidae) is the source of
      molecules that modulate splenic gene expression.
AB  - The clinical signs of a Sarcoptes scabiei (De Geer) (Acari: Sarcoptidae)
      infestation are initially delayed, which suggests that the mites can depress the
      immune/inflammatory response. The purpose of this study was to investigate the
      modulatory properties of scabies mites in vivo at the gene expression level in a
      secondary lymphoid organ that is involved in initiating an immune response to the
      parasite. We found that substances from scabies mites influenced the expression
      of mRNA for molecules that participate in the sequestering of lymphocytes in the
      periarteriolar lymphoid sheath, primary follicle, and marginal zone of the
      spleen. Mice exposed to live scabies mites exhibited decreased mRNA expression
      for the adhesion molecules intercellular adhesion molecule (ICAM)-1, ICAM-2 and L
      selectin; the cytokines tumor necrosis factor (TNF)alpha and CCL5; and the
      receptors for several other cytokines including TNF and interferon gamma. In
      addition, exposure to live mites or vaccination with a scabies extract resulted
      in reduced expression of mRNA for B7-2, CD40, CD4, CD8, and CD45, thereby
      potentially reducing the physical interactions between B cells and T-helper (Th)2
      helper cells, between Th1 and Tc cells, and between T-helper cells and antigen
      presenting cells, thus depressing their function in response to thymus-dependent
      antigen. Live scabies mites also depressed expression of toll-like receptors 2,
      4, and 6. In conclusion, our results indicate that live mites produce substances
      that can down-regulate expression of adhesion molecules, cytokines, chemokines,
      chemokine receptors, and lymphocyte surface molecules involved in leukocyte
      sequestering and the interaction of B and T cells during activation of an immune
      response in the spleen.

PMID- 18047207
TI  - Aedes albopictus and Culex pipiens implicated as natural vectors of Dirofilaria
      repens in central Italy.
AB  - To identify the natural vectors of Dirofilaria repens Railliet et Henry,
      entomological samplings were carried out in four sites within the Lazio region,
      foci of canine subcutaneous dirofilariasis. Collections were made in 2002-2003 by
      means of dog-baited and miniature Centers for Disease Control and Prevention
      traps as well as on humans. Microscopy identified 1576 attracted mosquito females
      as belonging to six species, but molecular diagnostics detected filarial DNA only
      in Culex pipiens L. and Aedes albopictus (Skuse, 1894). Dirofilaria immitis Leidy
      DNA, D. repens DNA, or both were found in the head and thorax of both mosquitoes.
      The simultaneous presence of vectors showing diurnal and nocturnal activity
      patterns is of concern for animal and human health. The finding of D. immitis DNA
      in mosquitoes in areas where only D. repens was been recovered in dogs also
      demonstrates that this filarial parasite circulates among carnivores (wild or
      domesticated pets).

PMID- 18047208
TI  - West Nile virus-infected dead corvids increase the risk of infection in Culex
      mosquitoes (Diptera: Culicidae) in domestic landscapes.
AB  - A comparative study of West Nile virus (family Flaviviridae, genus Flavivirus,
      WNV) infection rates in Culex mosquitoes collected at 13 sites, seven reporting
      WNV-positive dead corvids (case sites) and six without reported dead birds
      (control sites) was conducted in Davis, CA, from 14 to 21 July at the beginning
      of the 2006 WNV outbreak. In total, 3051 Culex mosquitoes were collected using
      gravid traps and CO2-baited traps; WNV-infected mosquitoes were only collected
      with CO2-baited traps. WNV-infected Culex pipiens L. were collected at one of the
      seven case sites. Six of seven case sites yielded WNV-infected Culex tarsalis
      Coquillett, whereas only one of six control sites had WNV-infected Cx. tarsalis.
      Overall, the odds of finding WNV-positive mosquitoes were 19.75 times greater at
      sites reporting a WNV-infected dead corvid than sites without a WNV-infected dead
      corvid. Maximum likelihood estimates of the overall infection rates at the case
      sites were 3.48/1000 for Cx. tarsalis and 8.69/1000 for Cx. pipiens compared with
      1.02/1000 in Cx. tarsalis collected at the control sites. Results indicate that
      Cx. tarsalis was important in early season enzootic transmission within Davis and
      that sites reporting WNV-infected dead corvids are areas to focus control and
      surveillance efforts.

PMID- 18047209
TI  - West Nile virus infection decreases fecundity of Culex tarsalis females.
AB  - West Nile virus (family Flaviviridae, genus Flavivirus, WNV) persistently infects
      many mosquito tissues, and it has been associated with cytopathological changes
      in midgut muscles and salivary glands. However, the effects of WNV infection on
      mosquito fitness (survival and reproduction) are not known. We conducted a life
      table study of individually housed female Culex tarsalis Coquillett. After an
      initial bloodmeal from a WNV-infected or uninfected chicken, mosquitoes were
      provided sucrose and offered weekly opportunities to feed on a hanging blood
      drop. WNV transmission status was determined by testing the remaining blood drop
      for virus after mosquito feeding. Dead mosquitoes and eggs were collected daily.
      Mosquito legs and bodies were tested for WNV, and eggs were counted and allowed
      to hatch. Two replicates of this experiment were performed, with a total of 62
      mosquitoes that fed on a WNV-infected chicken (of which 21 became infected) and
      43 mosquitoes that fed on an uninfected chicken. Fecundity of WNV-infected
      mosquitoes was significantly lower than that of uninfected mosquitoes, especially
      during the first oviposition. WNV infection was associated with smaller egg
      rafts, whereas increasing wing length and WNV titer in the legs had a positive
      effect on egg raft size. Additionally, infected mosquitoes had lower egg hatch
      rates than did uninfected mosquitoes. There were no significant differences in
      survival between infected and uninfected mosquitoes. Blood feeding rates were
      higher in infected mosquitoes than in uninfected mosquitoes. A small amount of
      virus (average, 378; range, 5-5000 plaque-forming units) was transmitted to the
      blood drops fed upon by infected mosquitoes. Although WNV infection negatively
      impacts mosquito reproduction, facets of mosquito biology that are critical to
      virus transmission success were either not affected (survival) or changed in such
      a way as to result in enhanced vectorial capacity (blood feeding).

PMID- 18047210
TI  - Anopheles kleini, Anopheles pullus, and Anopheles sinensis: potential vectors of
      Plasmodium vivax in the Republic of Korea.
AB  - Anopheles sinensis Wiedemann (63.3%) was the most abundant Anopheles mosquito
      captured at cowshed resting collections in malaria high-risk areas (northern
      Gyeonggi Province) near the demilitarized zone (DMZ) in Korea during 2005,
      followed by Anopheles kleini Rueda (24.7%) and Anopheles pullus M. Yamada (8.7%).
      At cowshed resting collections in malaria low-risk areas (Jeonnam and Gyeongnam
      provinces), An. sinensis accounted for 96.8% of all Anopheles spp. collected,
      followed by An. kleini Rueda (2.7%), whereas no An. pullus were collected. Three
      species, An. kleini (50.9%), An. pullus (29.0%), and An. sinensis (13.8%),
      accounted for nearly all of the 224 Anopheles spp. captured by New Jersey light
      trap near the DMZ. In addition, An. pullus and An. kleini captured by New Jersey
      light trap near the DMZ and assayed by enzyme linked immunosorbent assay for
      Plasmodium vivax circumsporozoite antigen concentrations were higher than An.
      sinensis sensu stricto (s.s.), indicating higher levels of sporozoites. In
      laboratory studies of four concurrent artificial membrane feedings on malaria
      infected blood from patients, F1 progeny of An. kleini and An. pullus had higher
      infection rates (8.8 and 7.5%, respectively) than An. sinensis s.s. (4.2%). These
      data suggest that An. kleini and An. pullus and An. sinensis are vectors of
      malaria in Korea. Further studies are required to determine the role of these
      species in the transmission of P. vivax in the Republic of Korea.

PMID- 18047211
TI  - Isolation of cell lines and a rickettsial endosymbiont from the soft tick Carios
      capensis (Acari: Argasidae: Ornithodorinae).
AB  - Soft ticks are medically important ectoparasites of birds and mammals that are
      found throughout the world. This report describes isolation and partial
      characterization of two embryonic cell lines, CCE2 and CCE3, from the seabird
      soft tick Carios capensis (Neumann). Sequencing of the mitochondrial 16S rRNA
      gene and karyology confirmed the lines were derived from C. capensis. CCE3 cells
      were diploid with a modal chromosome number of 20. The population doubling time
      for cell lines CCE2 and 3 in passage 40 was 6-9 d. A rickettsial endosymbiont,
      RCCE3, was co-isolated along with line CCE3. Nucleotide sequences of polymerase
      chain reaction (PCR) products generated using primers specific for rickettsial 17
      kDa antigen, outer membrane protein (omp) A, ompB, and citrate synthase genes
      along with phylogenetic analyses demonstrated that RCCE3 is a previously
      uncultured endosymbiont. The rickettsia was identified as a symbiont of C.
      capensis, closely related to rickettsiae previously detected by PCR in C.
      capensis, Ornithodoros moubata (Murray) and Hemaphysalis sulcata Canestrini &
      Fanzago, a hard tick. RCCE3 caused a cytopathic effect in C. capensis host cells,
      and it was transferred to Ixodes scapularis Say cell line ISE6 for maintenance.
      The rickettsial endosymbiont was eliminated from CCE3 by treatment with
      oxytetracycline. Cell lines from C. capensis will be useful to researchers
      investigating interactions between soft ticks and microorganisms, soft tick
      physiology, and molecular biology. The rickettsia adds to the growing number of
      Rickettsia species that have been isolated in tick cell culture, and it is
      available for characterization.

PMID- 18047212
TI  - Nocturnal activity of mosquitoes (Diptera: Culicidae) in a West Nile virus focus
      in Connecticut.
AB  - Six species of mosquitoes (Diptera: Culicidae) were collected in sufficient
      numbers for analysis in segregating traps set at 2-h intervals by using CO2 and
      light as attractants in a West Nile virus (family Flaviviridae, genus Flavivirus,
      WNV) focus in Stratford, CT. The Kolmogorov-Smirnov one-sided test for two
      samples was used to analyze the data. Mosquito activity began shortly before
      sunset and continued until shortly after sunrise the next morning. All species
      had geometric means that were significantly higher during the 2-h period shortly
      after sunset compared with the 2-h collection before sunset. Species, known to be
      naturally infected with WNV, were often attracted to these traps in about equal
      numbers at 2-h intervals during an 8- to 10-h period commencing shortly after
      sunset. Differences of geometric means were not significant among the four or
      five 2-h collection periods commencing at sunset for Aedes vexans (Meigen), Culex
      salinarius Coquillett, and Aedes cinereus Meigen. Aedes cantator (Coquillett) had
      a significantly higher geometric mean for the 2-h period commencing at sunset,
      and Coquillettidia perturbans (Walker) was captured in significantly greater
      numbers during the 2-h period starting at sunset compared with periods commencing
      6 h after sunset. Culex pipiens L. tended to have an activity pattern that was
      primarily nocturnal. Time of night, not meteorological conditions, was the most
      important factor in determining the nightly variation in the number of trapped
      mosquitoes. Parity rates of Cx. pipiens collected during specific periods of the
      night were not significant. In total, 39 isolations of WNV were made from seven
      species collected primarily during periods of total darkness. Humans are at risk
      of being bitten by infected mosquitoes throughout the night.

PMID- 18047213
TI  - Identification of host bloodmeal source and Borrelia burgdorferi sensu lato in
      field-collected Ixodes ricinus ticks in Chaumont (Switzerland).
AB  - To evaluate the importance of vertebrate species as tick hosts and as reservoir
      hosts in two endemic areas for Lyme borreliosis in Switzerland, we applied
      molecular methods for the analysis of bloodmeal source and Borrelia infection in
      questing Ixodes ricinus L. ticks. In total, 1326 questing ticks were
      simultaneously analyzed for Borrelia and for blood meal remnants by using reverse
      line blot. An overall infection prevalence of 19.0% was recorded for Borrelia
      sp., with similar rates in both sites. Using a newly developed method for the
      analysis ofbloodmeal targeting the 12S rDNA mitochondrial gene, identification of
      host DNA from field-collected ticks was possible in 43.6% of cases. Success of
      host identification at the genus and species level reached 72%. In one site, host
      identification success reached its maximum in spring (93% in May), decreasing in
      summer (20% in July) and rising in autumn (73% in October). In the other site,
      identification rate in ticks remained low from April to July and increased in
      autumn reaching 68% in October and November. The most prevalent identified host
      DNA was artiodactyls in both sites. Red squirrel DNA was significantly more
      frequently detected in ticks collected in one site, whereas insectivore DNA was
      more frequent in ticks in the other site. DNA from more than one vertebrate host
      was detected in 19.5% of nymphs and 18.9% of adults. Host DNA was identified in
      48.4% of the Borrelia infected ticks. Although DNA from all Borrelia species was
      found in at least some ticks with DNA from mammals and some ticks with DNA from
      birds, our results confirm a general association of B. afzelii and B. burgdorferi
      sensu stricto with rodents, and B. valaisiana and B. garinii with birds.

PMID- 18047214
TI  - Passive surveillance in Maine, an area emergent for tick-borne diseases.
AB  - In 1989, a free-of-charge, statewide tick identification program was initiated in
      Maine, 1 yr after the first Ixodes scapularis Say (=I. dammini Spielman,
      Clifford, Piesman & Corwin) ticks were reported in the state. This article
      summarizes data from 18 continuous years of tick submissions during which >24,000
      ticks of 14 species were identified. Data provided include tick stage, degree of
      engorgement, seasonal abundance, geographical location, host, and age of the
      person from whom the tick was removed. Maps depict the distributions of the three
      major species submitted. I. scapularis emerged first along the coast, and then it
      advanced inland up major river valleys, Dermacentor variabilis Say slowly
      expanded centrifugally from where it was initially reported in southwestern
      Maine, and the distribution of long-established Ixodes cookei Packard remained
      unchanged. Submissions of nymphal I. scapularis closely correlated with reported
      Lyme diseases cases at the county level. Annual fluctuations of nymphal
      submissions in Maine correlated with those of Lyme disease cases for New England,
      supporting the possibility of a regional influence on tick abundance. More ticks
      were removed from people < or =14 and > or =30 yr of age, and their degree of
      engorgement was greatest in people < or =20 yr of age and progressively increased
      in people > or =30 yr of age. This study demonstrates the usefulness and
      potential of tick identification programs.

PMID- 18047215
TI  - Climate niches of tick species in the Mediterranean region: modeling of
      occurrence data, distributional constraints, and impact of climate change.
AB  - In this study, we used ecological niche factor analysis (ENFA) and principal
      components analysis (PCA) of climate variables to define the climate niches and
      areas of potential colonization of six species of ticks in the Mediterranean
      region: Dermacentor marginatus Sulzer, Rhipicephalus bursa Canestrini & Fanzago,
      Rhipicephalus turanicus Pomerantsev, Matikashvili & Lototsky, Hyalomma marginatum
      Koch, Hyalomma excavatum Koch, and Boophilus annulatus (Say). ENFA generated
      distribution models that varied in accuracy from high to very high (area under
      the curve [AUC] = 0.87-0.97), with the lowest AUC obtained for B. annulatus. PCA
      provided an adequate separation of the climate niches of different species in the
      reduced space of the variables. Climate scenarios and factorial consensus
      analysis were used to evaluate the geographic impact of climate change (as
      turnover in habitat suitability) on the niches of the ticks and net variations in
      habitat availability. The scenario that was most compatible with estimates of
      future climate in the Mediterranean region (increase in temperature and decrease
      in rainfall) was predicted to produce a sharp increase in the extent of suitable
      habitat for R. bursa, R. turanicus, and H. marginatum. This scenario would result
      in a northward expansion of suitable habitat areas for these three species. The
      highest impact (highest species turnover) would be recorded at the margin of the
      current distribution range of the three species. A sensitivity analysis of the
      ecological response of the ticks to the climate change scenarios showed that the
      response is statistically different in different regions of the PCA-derived
      niche. These results outline the need to further investigate the potential of
      bioclimate models to obtain accurate estimations of tick species turnover under
      conditions of climate change over wide areas.

PMID- 18047216
TI  - Spatiotemporal investigation of adult mosquito (Diptera: Culicidae) populations
      in an eastern Iowa county, USA.
AB  - Landscape and climatic factors regulate distributions of mosquitoes (Diptera:
      Culicidae) over time and space. The anthropogenic control of mosquito populations
      is often carried out at a local administrative scale, and it is applied based on
      the relevant agency's experiential knowledge rather than systematic analysis of
      spatial and temporal data. To address this shortcoming, a spatial and temporal
      analysis of landscape and climatic parameters in relation to mosquito populations
      in Black Hawk County, IA, USA, has been carried out. Adult mosquito sampling took
      place using CDC light traps from May to August 2003 in representative landscapes.
      Mosquitoes were identified to species level with Aedes trivittatus (Coquillet)
      and Aedes vexans (Meigen) dominating the collection totals. The best publicly
      available spatial data on landscape and demographic attributes were collated and
      included land cover, human census, soils, floodplain, elevation, wetlands,
      hydrography, roads, and vegetation indices derived from satellite imagery.
      Spatial processing was carried out to organize landscape attributes for
      statistical comparison with abundance data from the potentially important West
      Nile virus (family Flaviviridae, genus Flavivirus, WNV) vector species Ae. vexans
      and Ae. trivittatus. Landscape parameters shown to be significantly correlated
      with mosquito counts included soil hydrological properties, presence in
      floodplain, wetland areas, and deciduous and bottomland forest cover. Data on
      temperature and precipitation were used to investigate the climatic influence on
      the temporal occurrence of mosquito population abundances. Late spring rain
      provided ample moisture for mosquito development, but low temperatures delayed
      widespread emergence of Ae. trivittatus and Ae. vexans until June 2003. Landscape
      and climatic impacts on adult mosquito population distributions were
      demonstrated, and these results could form the basis for the development of a
      spatiotemporal modeling framework that would inform anthropogenic mosquito
      control anld vector-borne disease surveillance. A qualitative discussion
      concerning Culex pipiens (L.) and Culex restuans Theobald is included.

PMID- 18047217
TI  - Spontaneous recovery after reversal and partial reinforcement.
AB  - Six experiments used magazine approach in rat subjects to explore changes with
      time in responding for stimuli brought to a common moderate level of performance
      through acquisition or extinction. They found no evidence for increases with time
      in behavior during stimuli given simple acquisition. However, stimuli brought to
      that same level by reversal learning, repeated reversal, or partial reinforcement
      all showed increases in responding with time. These results suggest that the
      decremental process established by nonreinforcement endures through subsequent
      reinforcement and is especially sensitive to the passage of time.

PMID- 18047218
TI  - CS-duration and partial-reinforcement effects counteract overshadowing in select
      situations.
AB  - Two experiments used rats in a conditioned lick suppression preparation to
      investigate how the conditioned stimulus (CS)-duration and partial-reinforcement
      effects (i.e., weakened responding due to conditioning with a CS of longer
      duration and presenting nonreinforced CSs intermingled with CS-unconditioned
      stimulus [US] pairings, respectively) interact with overshadowing. Experiment 1
      found that when overshadowing treatment was combined with either extended CS
      duration or partial reinforcement, the response deficit was weaker than when
      either of these three treatments was administered alone. In Experiment 2, the
      generality of the findings in Experiment 1 was investigated by replicating it
      with various US-US intervals. This time counteraction was observed only when both
      the absolute duration of total CS exposure and the US-US interval were short. The
      results support neither the view that the ratio between the total CS exposure and
      total time in the context determines the CS-duration and the partial
      reinforcement effects nor the view that these two effects arise from a loss of
      effectiveness of the excitatory CS-US association during CS-alone exposures in
      partial reinforcement or early periods of CS exposure with long CSs.

PMID- 18047220
TI  - Discrimination learning in humans: role of number and complexity of rules.
AB  - Various types of discrimination learning tasks, such as so-called nonconditional,
      conditional, and biconditional tasks, are generally held to differ in complexity
      and to require different amounts of training. However, rather than a difference
      in rule complexity, between-task performance differences may reflect a difference
      in number of underlying rules. Accordingly, in the present study, human
      participants were subjected to tasks differing in number and/or complexity of
      rules. In Experiments 1 and 3, participants learned to differentially respond to
      visual-target stimuli, each of which was preceded by a visual feature. Conditions
      differed in the number of different features and in the informational value of
      individual features and/or targets. In Experiment 2, participants were fully
      informed about all relevant stimulus-response mappings prior to each trial.
      Performance accuracy was primarily determined by number of underlying rules in
      the initial phase of discrimination learning, especially when the time available
      for responding was restricted. However, when participants had attained a high
      accuracy level, performance was solely determined by rule complexity. Apparently,
      number and complexity of rules have a different weight, depending on the stage of
      discrimination learning.

PMID- 18047219
TI  - Place versus response learning in rats.
AB  - In previous research designed to test whether place learning or response learning
      proceeds more quickly and better in rats, place has not been defined
      unambiguously when direction has been controlled by moving an apparatus around in
      the test room (Blodgett, McCutchan, & Mathews, 1949; Skinner et al., 2003). In
      Experiment 1, we compared place and response learning while controlling direction
      in a static apparatus, thus making the meaning of place unambiguous. The
      performance of rats that had to make different turns to find food in a particular
      place and rats that had to always make the same turn to find food in two
      different places did not differ. In Experiment 2, visual cues were made equally
      discriminable for place and response learners in a static apparatus. Place
      learners still failed to outperform response learners, but there was evidence
      that response biases interfered more with place than with response learning. The
      results are discussed with reference to the historical debate that generated the
      original research and also in terms of morecontemporary spatial-learning issues
      in rats.

PMID- 18047221
TI  - Flavor evaluative conditioning and contingency awareness.
AB  - The relationship between flavor evaluative conditioning and contingency awareness
      was examined intwo experiments using flavored drinks. In Experiment 1, one flavor
      was always paired with sugar and the other with bitter tween (polysorbate20)
      during conditioning. In a subsequent test phase, participants tasted the two
      flavors, and their evaluative ratings indicated an overall preference for the
      sugar-paired flavor. Moreover, participants were generally able to report which
      flavor had been paired with sugar and which with tween. This finding was
      replicated and confirmed in Experiment 2A. Furthermore, in both experiments,
      evaluative conditioning was seen only in those participants who were aware of the
      contingencies. Experiment 2B demonstrated that evaluative conditioning does not
      occur to colors, although participants are contingency aware. The differences
      between the present findings and prior studies, in which apparently unaware
      flavor conditioning has been found, are discussed.

PMID- 18047222
TI  - Matching-to-sample in pigeons: in the absence of sample memory, sample frequency
      is a better predictor of comparison choice than the probability of reinforcement
      for comparison choice.
AB  - In matching-to-sample, comparison choice should be controlled by the identity of
      the sample and, when the sample is not available, by the overall probability of
      reinforcement associated with each of the comparisons. In the present research,
      pigeons were trained to match a frequent sample (appearing on 80% of the trials)
      to one comparison (C(fr)) and an infrequent sample (appearing on 20% of the
      trials) to the other (C(inf)), with the number of reinforcements associated with
      each sample equated. In Experiment 1, the task was identity matching; in
      Experiments 2 and 3, it was symbolic matching. We asked whether, when control of
      comparison choice by the sample was reduced (by inserting a delay between the
      sample and the comparisons), pigeons would choose comparisons on the basis of (1)
      the number of reinforcements per comparison (and thus show no comparison bias),
      (2) the comparison associated with the more frequent sample during training (and
      show a preference for C(fr)), or (3) the probability of reinforcement given a
      correct response (and show a preference for C(inf)), or (4) inhibition produced
      by nonreinforced choice of the more frequently correct comparison (and show a
      preference for C(inf)). Pigeons showed a significant tendency to choose C(fr). In
      Experiment 3, we showed that this bias did not result from the effects of
      intertrial facilitation or interference. Thus, it appears that when control of
      comparison choice by the sample is reduced, pigeons' choice is controlled not
      merely by the probability of reinforcement but also by overall sample frequency.

PMID- 18047223
TI  - Sample and comparison location as factors in matching acquisition, transfer, and
      acquired equivalence.
AB  - Pigeons learned symbolic matching with samples appearing equally often on left
      and right keys. For a location-relevant group, the reinforced comparison choice
      for each sample reversed across sample locations; for a location-irrelevant
      group, the reinforced choices were the same. Consistent with the hypothesis that
      samples at different locations are functionally different for pigeons, Experiment
      1 showed that matching acquisition was comparable in these two groups.
      Nevertheless, the location-irrelevant group eventually ignored sample location,
      given that their performances subsequently transferred to a novel (center-key)
      sample location. This transfer was not simply due to sample familiarity at
      different training locations; rather, it required that left- and right-key
      samples occasion the same reinforced choices in training. Acquired equivalence
      between those samples was then assessed in Experiment 2. The location-irrelevant
      group showed the predicted equivalence effects, but the location-relevant group
      did not--in fact, its results were the opposite of those predicted by
      equivalence. Their results indicate that the functional comparison stimuli are
      also defined in terms of their locations.

PMID- 18047225
TI  - Numerosity discrimination in preschool children.
AB  - We used a numerical bisection procedure to examine preschool children's
      sensitivity to the numerical attributes of stimuli. In Experiment 1 children
      performed two tasks. In the Cups Task they earned coins for choosing a green cup
      after two drumbeats and a blue cup after eight drumbeats. In the Gloves Task they
      earned coins for raising a red glove on their left hand after two drumbeats and a
      yellow glove on their right hand after eight drumbeats. Then in each task a
      psychometric function was obtained by presenting intermediate numerosities and
      recording the percentage of trials in which children chose the "many" option. In
      Experiment 2 children's performance in a '2 vs. 8' discrimination was compared
      with their performance in a "4 vs. 16" discrimination. Results showed that the
      individual psychometric functions were of two types, one in which the percentage
      of "many" choices increased gradually with stimulus numerosity and another in
      which it increased abruptly, in a step-like manner. Although the average point of
      subjective equality was close to the geometric mean of the anchor numerosities
      and the average functions for "2 vs. 8" and "4 vs. 16" superimposed when plotted
      on a common scale (the scalar property), the individual data were highly variable
      both across tasks (Cups and Gloves) and numerosity ranges ('2 vs. 8' and '4 vs.
      16'). It is suggested that between- and within-subjects variability in the
      psychometric function is related to children's verbalizations about the sample
      stimulus.

PMID- 18047224
TI  - Aging and intraindividual variability in performance: analyses of response time
      distributions.
AB  - It has been suggested that older adults are more variable in their performance
      because they are more prone to lapses of either attention or intention. In the
      present experiment, 9 young and 9 older adults each performed nearly 2000 trials
      of a same-different judgment task. As expected, older adults were slower and more
      variable than young adults. When the age-related difference in speed was taken
      into account, however, the older adults were, if anything, less variable than the
      young adults. When younger and older adults' RT distributions were analyzed using
      quantile-quantile plots and by fitting ex-Gaussian and Weibull functions, there
      was no consistent evidence that older adults' distributions were more skewed than
      young adults', as would be predicted by age-related increases in lapses of
      attention or intention. Importantly, there was a positive, linear relation
      between RT and intraindividual variability, and the same relation was observed
      both within subjects (practice increased speed and reduced variability) as well
      as between subjects (regardless of age, slower individuals were more variable).
      Thus, the present results suggest that there may be a general law governing the
      relation between average RT and variability, and that the greater performance
      variability of older adults primarily reflects their greater average RTs.

PMID- 18047226
TI  - Tests of behavioral-economic assessments of relative reinforcer efficacy II:
      economic complements.
AB  - This experiment was conducted to test the predictions of two behavioral-economic
      approaches to quantifying relative reinforcer efficacy. The normalized demand
      analysis suggests that characteristics of averaged normalized demand curves may
      be used to predict progressive-ratio breakpoints and peak responding. By
      contrast, the demand analysis holds that traditional measures of relative
      reinforcer efficacy (breakpoint, peak response rate, and choice) correspond to
      specific characteristics of non-normalized demand curves. The accuracy of these
      predictions was evaluated in rats' responding for food or water: two reinforcers
      known to function as complements. Consistent with the first approach, predicted
      peak normalized response output values obtained under single-schedule conditions
      ordinally predicted progressive-ratio breakpoints and peak response rates
      obtained in a separate condition. Combining the minimum-needs hypothesis with the
      normalized demand analysis helped to interpret prior findings, but was less
      useful in predicting choice between food and water--two strongly complementary
      reinforcers. Predictions of the demand analysis had mixed success. Peak response
      outputs predicted from the non-normalized water demand curves were significantly
      correlated with obtained peak responding for water in a separate condition, but
      none of the remaining three predicted correlations was statistically significant.
      The demand analysis fared better in predicting choice--relative consumption of
      food and water under single schedules of reinforcement predicted preference under
      concurrent schedules significantly better than chance.

PMID- 18047227
TI  - Age trends in stimulus overselectivity.
AB  - Stimulus overselectivity refers to the phenomenon whereby stimulus control over
      behavior is exerted only by a limited subset of the total number of stimuli
      present during discrimination learning. It often is displayed by individuals with
      autistic spectrum disorders or learning disabilities, but is not exclusive to
      those groups. The present studies investigated the impact of aging on stimulus
      control and overselectivity. Three age groups--18-22, 47-55, and 70-80 year olds
      were studied in two experiments. All participants were trained on a simple
      discrimination task, randomly assigned to one of two conditions (either with or
      without a distractor task), and then tested for the emergence of overselectivity
      (Experiment 1). In Experiment 2 responding controlled by the overselected
      stimulus elements was reduced by introducing a verbal punisher. In subsequent
      tests, control of behavior by the previously underselected elements from
      Experiment 1 was enhanced across the two younger age groups but not the oldest
      group of participants. The results are discussed in relation to the attention
      deficit and overshadowing accounts of overselectivity.

PMID- 18047228
TI  - Effects of differing response-force requirements on food-maintained responding in
      CD-1 mice.
AB  - The effect of force requirements on response effort was examined using outbred
      (CD-1) mice trained to press a disk with their snout. Lateral peak forces greater
      than 2 g were defined as threshold responses (i.e., all measured responses).
      Different force requirements were used to define criterion responses (a subclass
      of threshold responses) that exceeded the requirement. The reinforcer was
      sweetened, condensed milk, and it was delivered upon response termination. All
      mice were exposed to two ascending series of criterion force requirements (2, 4,
      8, 16, and 32 g). Increasing the force requirement decreased criterion response
      rates, but increased threshold response rates. The time-integral of force (area
      under the force-time curve for individual responses, which is proportional to
      energy expenditure for each response) increased with the increase in the force
      requirement. These results conflict with the hypothesis that higher force
      requirements have aversive qualities and suggest that increased force
      requirements are more analogous to intermittent schedules of reinforcement. These
      data suggest that estimations of effort or energy expenditure should be measured
      independently of the force requirement. Individual differences in responding were
      found for the CD-1 outbred stock.

PMID- 18047229
TI  - Seasonal variation in pigeon body weight and delayed matching-to-sample
      performance.
AB  - The weights of 5 pigeons with free access to food, monitored over 3 calendar
      years in the laboratory, were found to fluctuate with season. All pigeons were at
      their heaviest in the winter and were lightest in the summer. Five different
      pigeons performed a standard delayed matching-to-sample task for 44 weeks from
      January to November. Their weights were held at 85% of their summer free-feeding
      weights, making their predicted deprivation level higher in the winter relative
      to predicted winter free-feeding weights. Slopes of forgetting functions fit to
      weekly response totals for each pigeon were shallower in winter, showing an
      improvement in accuracy with longer delays. Thus, delayed matching-to-sample
      performance may have been affected by the practice of maintaining the pigeons at
      a constant body weight throughout the calendar year.

PMID- 18047231
TI  - Epidemiological aspects on apical periodontitis. Studies based on the Prospective
      Population Study of Women in Goteborg and the Population Study on Oral Health in
      Jonkoping, Sweden.
AB  - The objectives of this thesis were to describe endodontic status in Swedish
      populations, to study clinical and socio-economic risk factors for apical
      periodontitis (AP) and to explore a possible association between AP and coronary
      heart disease (CHD). In papers I, II and IV the Prospective Study of Women in
      Goteborg (PSWG) was used. In paper I dentate women examined in 1968-69 (N=1220),
      1980-81 (N=1023) and 1992-93 (N=867) were included for cross-sectional and
      longitudinal (N=586) analysis of endodontic status over 24 years in individuals
      aged 38-84 years. In papers III and IV a cross-sectional sample (N=844 and N=867,
      respectively) from 1992-93 was used for exploring associations between AP, socio
      economic risk factors and CHD in multivariate logistic regression models. In
      paper II random samples of dentate individuals aged 20-70 years from the
      Population Study on Oral Health in Jonkoping (PSJ) were used. The first
      examination in 1973 (N=498) was followed by new examinations in 1983 (N=530),
      1993 (N=547) and 2003 (N=491). Full mouth radiographic examinations were
      restudied, yielding 3981 root filled teeth for the analysis. AP was recorded
      according to the Periapical Index (PAI) and the root filling quality was assessed
      with respect to length and seal. The association between root filling quality and
      AP was studied on the tooth-level as well as on the individual level. The results
      from multivariate logistic regression analysis did not reveal a significant
      association between AP and CHD and socio-economic risk factors and AP,
      respectively. The ratio of root filled teeth increased with age longitudinally
      and cross-sectionally, but decreased over time for comparable age groups. The
      ratio of AP increased with age cross-sectionally, but decreased with age
      longitudinally and for comparable age groups over time. Inadequate root filling
      quality was predictive of AP with an odds ratio of 4.5. The root filling quality
      was improved over time without a concomitant decrease in ratio of root filled
      teeth with AP.

PMID- 18047230
TI  - An experimental analysis of memory processing.
AB  - Rhesus monkeys were trained and tested in visual and auditory list-memory tasks
      with sequences of four travel pictures or four natural/environmental sounds
      followed by single test items. Acquisitions of the visual list-memory task are
      presented. Visual recency (last item) memory diminished with retention delay, and
      primacy (first item) memory strengthened. Capuchin monkeys, pigeons, and humans
      showed similar visual-memory changes. Rhesus learned an auditory memory task and
      showed octave generalization for some lists of notes--tonal, but not atonal,
      musical passages. In contrast with visual list memory, auditory primacy memory
      diminished with delay and auditory recency memory strengthened. Manipulations of
      interitem intervals, list length, and item presentation frequency revealed
      proactive and retroactive inhibition among items of individual auditory lists.
      Repeating visual items from prior lists produced interference (on nonmatching
      tests) revealing how far back memory extended. The possibility of using the
      interference function to separate familiarity vs. recollective memory processing
      is discussed.

PMID- 18047232
TI  - The relationship of social support to depressive symptoms during the transition
      to high school.
AB  - The transition to high school is studied as a time when students may experience
      disruptions in their social support systems. Peer support, family support, and
      school belonging were hypothesized to be associated with adolescent adjustment,
      specifically depressive symptoms. Participants included 104 eighth graders and
      101 ninth graders from a middle- to high-income, predominantly white community in
      southern Rhode Island. In year 2, 60 of the original 8th graders were surveyed as
      9th graders. Three hypotheses were examined: Social support declines from 8th to
      9th grade; depressive symptoms increase from 8th to 9th grade; and social support
      is significantly associated with depressive symptoms. The hypotheses were tested
      using cross-sectional and longitudinal analyses. Results indicated that 9th
      graders experienced more depressive symptoms and lower levels of school belonging
      as compared to the 8th graders. Changes in parent support and peer support were
      significantly associated with depressive symptoms in the transition to high
      school. Implications for increasing school belonging in the 9th grade are
      discussed.

PMID- 18047233
TI  - Aggressive adolescents in residential care: a selective review of treatment
      requirements and models.
AB  - This article presents a selective inventory of treatment methods of aggressive
      behavior. Special attention is paid to types of intervention that, according to
      research, are frequently used in Dutch residential youth care. These methods are
      based on (1) principles of (cognitive) behavior management and control, (2) the
      social competence model, and (3) influencing the peer culture. Suggestions are
      made as to how the treatment of aggressive adolescents may be realized in
      residential settings. The article concludes that more attention should be paid to
      the involvement of parents and to the part played by the peer group in the
      treatment of aggressive behavior.

PMID- 18047234
TI  - Adolescent perception of mothers' parenting strengths and needs: a cross-cultural
      approach to curriculum development for parent education.
AB  - Black, Hispanic, and White American early adolescents (N = 573) were administered
      the Parent Success Indicator. The performance of their mothers was rated for 60
      items, included within six subscales, that consider Communication, Use of Time,
      Teaching, Frustration, Satisfaction, and Information Needs. Each racial group
      described favorable attributes of mothers and noted realms of learning where
      further growth seemed warranted. Statistically significant main effects for race,
      time spent together, and presence of an adult at home when the adolescent
      returned from school were reported. No significant main effects for child gender
      were reported. Based on perceptions of the participants, topics were identified
      for a common parent curriculum that can serve mothers of each racial group.
      Additional topics, based on the ratings within each race, were recommended to
      meet the distinctive learning needs of Black, Hispanic, and White mothers of
      early adolescents.

PMID- 18047235
TI  - Adolescents' views on war and peace in the early phases of the Iraq conflict.
AB  - Adolescents' views of war and peace were assessed among 209 children aged 10-14
      who attended a parochial school or its after-school religious program located in
      a predominantly middle-class, suburban area within commuting distance of New York
      City. Findings were compared to those of youth surveyed during other armed
      conflicts, specifically the Vietnam War, the first Persian Gulf War, and the U.S.
      military involvement in Latin America. The study took place in early fall 2003,
      and results were interpreted in light of the social climate and complex realities
      of post 9/11 in New York State, the Catholic Church's initial opposition to the
      Iraq conflict, and popular opinion. In spite of differences between the Iraq War
      and other conflicts, findings are remarkably similar. Although the present group
      is highly preoccupied with terrorism and nuclear war, even in a time of war,
      participants show concern for what they perceived as affecting their lives
      directly, rather than with conventional war. While they believe that President
      Bush was honest about the war in Iraq and right in sending troops, they do not
      glorify war. On a theoretical level, they overwhelmingly believe that wars are
      bad and the majority is optimistic that world peace is possible, though they
      realize that wars are difficult to prevent, believe that they are sometimes
      needed, and will occur in the future. Unlike the Catholic group surveyed by
      Tolley during the Vietnam War, however, participants are not as ready to die for
      their country, although findings show that, overall, like past groups, more boys
      tend to be pro-war than are girls and participants' views tend to reflect
      contemporary public opinions.

PMID- 18047236
TI  - Time perspective and school membership as correlates to academic achievement
      among African American adolescents.
AB  - This study examined the relationship of academic achievement to time perspective
      (future, present) and school membership (belonging, acceptance, rejection) among
      232 low-income, urban African American adolescents. Findings indicated positive,
      significant relationships among academic achievement, future time perspective,
      school belonging, and school acceptance. A negative, significant relationship was
      found between academic achievement and present time perspective. Based on
      multiple regression analysis, the ability of time perspective and school
      membership to predict academic achievement differed across gender. Whereas
      present time perspective was predictive of academic achievement among males,
      school acceptance and future time perspective emerged as significant predictors
      of academic achievement among females. Present time perspective contributed
      negatively to academic achievement among males, while school acceptance and
      future time perspective contributed positively to academic achievement among
      females.

PMID- 18047237
TI  - Bedroom design and decoration: gender differences in preference and activity.
AB  - This investigation examined gender differences in niche-building preference and
      activity among 238 8th and 9th grade boys and girls. A questionnaire was
      developed to measure both the actual and preferred bedroom content, bedroom
      design activity, and the level of perceived influence by the immediate and
      extended family, friends, and social institutions. Gender differences were
      identified for preference, activity, and influence in bedroom design and
      decoration. Girls and boys differed in the type of items contained in their
      bedrooms. Girls' rooms contained stuffed animals and pictures of people,
      including themselves, more frequently than the boys' rooms. In contrast, boys'
      rooms contained sports-related items, and things for building or that they had
      built themselves. Although bedroom design activity for both boys and girls was
      influenced by older teens, friends, media, and popular culture, boys (but not
      girls) were also influenced by their mothers, fathers, girlfriends, and
      activities such as sports, Boy or Girl Scouts, and music lessons.

PMID- 18047238
TI  - Empowering school social work practices for positive youth development: Hong Kong
      experience.
AB  - Empowerment has become a popular concept in working with adolescents in recent
      years. It challenges the deficit model of youth work and focuses on creating a
      facilitative climate in which young people can make maximum use of the
      opportunity to learn and grow. While many practitioners have adopted the
      empowerment approach in youth services, however, we know little about the
      possibilities for empowerment practice in the field of school social work. Based
      on the findings of a qualitative study conducted in Hong Kong, this paper
      explores how school social workers engage in different dimensions of empowerment:
      (1) the personal dimension in regard to how students recapture a sense of
      competence to meet life challenges and fight for their own benefits; (2) the
      school and community dimensions in regard to how practitioners collaborate with
      service users and partners to initiate constructive changes to school policies
      and strengthen the school-community partnership for student development; and (3)
      the institutional dimension in regard to how practitioners play the advocacy role
      in the education sector. The findings provide rich information for other youth
      workers, especially those who render service in the school setting, as they apply
      the empowerment approach in daily practice.

PMID- 18047239
TI  - Perceived parental behavioral control and psychological control in Chinese
      adolescents in Hong Kong: a replication.
AB  - Perceived paternal and maternal behavioral control (including dimensions of
      parental knowledge, expectation, monitoring, discipline and demandingness) and
      psychological control in 2,748 Chinese Secondary 2 students were examined.
      Results showed that two stable dimensions (paternal and maternal behavioral
      control) were extracted from the parental behavioral control measures. Although
      different dimensions of parental behavioral control were inter-related, parental
      monitoring was the strongest predictor of parental knowledge. Regarding the
      relationship between behavioral control and psychological control, composite
      parental behavioral control measures were weakly related to parental
      psychological control and different aspects of parental behavioral control were
      differentially related to parental psychological control. The present findings
      replicated previous findings based on Chinese Secondary 1 students.

PMID- 18047240
TI  - Impetus for worship: an exploratory study of adolescents' idol adoration
      behaviors.
AB  - The objective of this article is to explore the idolization behaviors of
      Taiwanese adolescents. The study gathered 1,636 questionnaires from 13 senior
      high schools across northern, central, southern, and eastern Taiwan. The results
      indicate that adolescents' gender correlates with the idol type they choose to
      adore when the idol is male. This study summarizes "exterior," "interior,"
      "wealth," and "athlete" as four underlying idol traits attracting adolescents.
      Various types of idols are considered to be significantly different on these four
      traits. The impacts of the four traits on adolescents' worship levels are
      nonsymmetrical. While the traits of exterior and athlete are worship
      facilitators, the trait of wealth is a prohibitor. By contrast, the trait of
      interior is neutral and has no effect on worship levels. Furthermore, adolescents
      are involved in higher levels of worship when the idol is a media star or is the
      opposite gender of the adolescent. Generally, adolescents' worship levels are
      heightened by the illusion of a perfect idol, indicating nonrational worship
      behaviors. Implications regarding the association between adolescents' cognitive
      abilities and idols' traits are discussed for future research.

PMID- 18047241
TI  - Migration and psychological status of adolescents in Turkey.
AB  - The aim of this study was to investigate the influence of involuntary migration
      on an adolescent population that had moved with their families to either one of
      two culturally different locations in Turkey. One of these groups had moved from
      a village in Eastern Turkey to a nearby town, while the other had moved a
      considerable distance to a large city in Western Turkey. Comparison groups
      included adolescents from both regions who had never migrated. Measures of self
      esteem, satisfaction with life, and social support networks were used with 305
      adolescents who were between the ages of 12 and 15. Adolescents who had migrated
      scored lower on self-esteem and life satisfaction, and had fewer people in their
      social support networks than those who had not. It was also found that those who
      had migrated tended to be more dependent on peers than family for social support.
      This was probably the case because school attendance was lower for migrants,
      particularly for males, and the probability of full time work on the street away
      from their families was considerably higher.

PMID- 18047242
TI  - Exploration of the prevalence and correlates of substance use among sheltered
      adolescents in South Korea.
AB  - Substance use among sheltered adolescents is very serious in South Korea--a
      nation in the process of rapid industrialization and urbanization. However, few
      studies have investigated substance use among the adolescents which is a growing
      concern of the changing society of this nation. This study examined the
      prevalence of substance use and explored risk factors that predict substance
      abuse by sheltered adolescents. Through a questionnaire survey of sheltered
      adolescents, data on substance use and the risk factors were collected. The
      sample of the adolescents included 44 (33.3%) males and 88 (67.2%) females; their
      mean age was 15.8 years (SD = 1.62). The results of a logistic regression
      analysis showed that alcohol expectancy, physical abuse, and peer pressure were
      all statistically significantly associated with substance abuse. Findings on the
      critical issues are expected to lead to the development of urgently needed
      prevention programs for the high-risk adolescents in South Korea.

PMID- 18047243
TI  - Reducing wastewater amalgam: the next step.

PMID- 18047244
TI  - The sovereignty of dentistry.

PMID- 18047245
TI  - The illegal practice of denturism.

PMID- 18047246
TI  - The cost of continuing education: who pays the bill?

PMID- 18047247
TI  - Confessions of a career day presenter.

PMID- 18047249
TI  - Following national trends, MDA "Blues" rates to increase.

PMID- 18047248
TI  - Are dental services coming to a franchise near you?

PMID- 18047250
TI  - "Steel Water" rises in Grand Rapids.

PMID- 18047251
TI  - Getting the most from your hygiene department.

PMID- 18047252
TI  - The basis for decisions to end life. The Schiavo dilemma: an essay by the special
      guardian ad Litem.

PMID- 18047253
TI  - The older driver: who is responsible? The state, the doctor, or the older driver?

PMID- 18047255
TI  - Improving the gastrointestinal tolerability of aspirin in older people.
AB  - Interventions to reduce mortality and disability in older people are vital.
      Aspirin is cheap and effective and known to prevent cardiovascular and
      cerebrovascular disease, many cancers, and Alzheimer dementia. The widespread use
      of aspirin in older people is limited by its gastrointestinal side effects.
      Understanding age-related changes in gastrointestinal physiology that could put
      older people at risk of the side effects of aspirin may direct strategies to
      improve tolerance and hence lead to greater numbers of older people being able to
      take this effective intervention.

PMID- 18047256
TI  - Clinical interventions for late-life anxious depression.
AB  - Anxiety symptoms are frequently present in patients with late-life depression.
      The designation "anxious depression" has been used to describe major depressive
      disorder (MDD) accompanied by clinically significant but subsyndromal anxiety
      symptoms. MDD may also present comorbid with diagnosable anxiety disorders,
      although this presentation is less common in late life. Diagnosis of anxious
      depression in the elderly is complicated by several factors (eg, their tendency
      to experience and report psychiatric symptoms as somatic illness) and is
      associated with a more severe clinical presentation, increased risk for suicidal
      ideation, increased disability, and poorer prognosis. Standard pharmacotherapy
      for depression may be sufficient but for many patients must be modified or
      augmented. Psychosocial interventions may also be an important component in the
      treatment of these patients, although no specific psychosocial treatments have
      been developed for late-life anxious depression.

PMID- 18047257
TI  - Skin treatments and dermatological procedures to promote youthful skin.
AB  - The skin, the largest organ of the body, is the organ in which changes associated
      with aging are most visible. With increasing frequency, patients are requesting
      information and treatments that improve the appearance of their skin.
      Corresponding to this trend, there is an increasing number of products and
      methods available that claim to aid this pursuit. First, a change of the
      patient's lifestyle (eg, sun behavior, nicotine abuse, and nutrition) must take
      place. Only then may other methods be used. This article reflects on the
      following topics: topical retinoids, peels, botulinum neurotoxin, soft tissue
      fillers, lasers, topical and systemic endocrinological therapies, and
      phytohormones. A thorough knowledge of the properties (benefits, limitations, and
      complications) of the expanding array of possibilities for rejuvenation of the
      skin is essential for any physician treating patients with cosmetic complaints.

PMID- 18047258
TI  - Cardiovascular assessment of falls in older people.
AB  - Falls in older people can be caused by underlying cardiovascular disorders,
      either because of balance instability in persons with background gait and balance
      disorders, or because of amnesia for loss of consciousness during unwitnessed
      syncope. Pertinent investigations include a detailed history, 12-lead
      electrocardiography, lying and standing blood pressure, carotid sinus massage
      (CSM), head-up tilt, cardiac electrophysiological tests, and ambulatory blood
      pressure and heart rate monitoring, which includes external and internal cardiac
      monitoring. The presence of structural heart disease predicts an underlying
      cardiac cause. Conversely, the absence of either indicates that neurally mediated
      etiology is likely. CSM and tilt-table testing should be considered in patients
      with unexplained and recurrent falls. Holter monitoring over 24 hours has a low
      diagnostic yield. Early use of an implantable loop recorder may be more cost
      effective. A dedicated investigation unit increases the likelihood of achieving
      positive diagnoses and significantly reduces hospital stay and health
      expenditure.

PMID- 18047254
TI  - Dietary approaches that delay age-related diseases.
AB  - Reducing food intake in lower animals such as the rat decreases body weight,
      retards many aging processes, delays the onset of most diseases of old age, and
      prolongs life. A number of clinical trials of food restriction in healthy adult
      human subjects running over 2-15 years show significant reductions in body
      weight, blood cholesterol, blood glucose, and blood pressure, which are risk
      factors for the development of cardiovascular disease and diabetes. Lifestyle
      interventions that lower energy balance by reducing body weight such as physical
      exercise can also delay the development of diabetes and cardiovascular disease.
      In general, clinical trials are suggesting that diets high in calories or fat
      along with overweight are associated with increased risk for cardiovascular
      disease, type 2 diabetes, some cancers, and dementia. There is a growing
      literature indicating that specific dietary constituents are able to influence
      the development of age-related diseases, including certain fats (trans fatty
      acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular
      disease, glycemic index and fiber for diabetes, fruits and vegetables for
      cardiovascular disease, and calcium and vitamin D for osteoporosis and bone
      fracture. In addition, there are dietary compounds from different functional
      foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols
      that may affect the development of age-related diseases. Long-term prospective
      clinical trials will be needed to confirm these diet-disease relationships. On
      the basis of current research, the best diet to delay age-related disease onset
      is one low in calories and saturated fat and high in wholegrain cereals, legumes,
      fruits and vegetables, and which maintains a lean body weight. Such a diet should
      become a key component of healthy aging, delaying age-related diseases and
      perhaps intervening in the aging process itself. Furthermore, there are studies
      suggesting that nutrition in childhood and even in the fetus may influence the
      later development of aging diseases and lifespan.

PMID- 18047260
TI  - Vitamins in aging, health, and longevity.
AB  - Evidence of epidemiological associations of vitamins and disease states have been
      found for nine vitamins. In observational studies, people with a high intake of
      antioxidant vitamins by regular diet or as food supplements generally have a
      lower risk of major chronic disease, such as myocardial infarction or stroke,
      than people who are low consumers of antioxidant vitamins. Prospectively, folate
      appears to reduce the incidence of neural tube defects. Vitamin D is associated
      with a decreased occurrence of fractures when taken with calcium. Zinc,
      betacarotene, and vitamin E appear to slow the progression of macular
      degeneration, but do not reduce the incidence. Vitamin E and lycopene may
      decrease the risk of prostate cancer. In other randomized controlled trials, the
      apparent beneficial results of a high intake of antioxidant vitamins seen in
      observational studies have not been confirmed. There is increasing concern from
      these trials that pharmacological supplementation of vitamins may be associated
      with a higher mortality risk.

PMID- 18047261
TI  - The ensemble of hetero-proteins in inorganic nanochannels.
AB  - The assembly and proper alignment of two heterofluorescent proteins (sGFP and
      DsRed) in the mesoporous channels of ethanol-treated FSM6.2 (a folded-sheet
      mesoporous material with a pore diameter of 6.2 nm) was confirmed using a
      fluorescence resonance energy transfer (FRET) technique. The sGFP-DsRed-FSM6.2
      conjugate showed a large decrease in the emission of donor (sGFP) fluorescence,
      indicating that the conjugate functions as an energy transfer system through the
      combination of the two heteroproteins, due to the successful encapsulation of the
      sGFP-DsRed pairs in the mesopores. Fluorescence spectral analysis demonstrated
      that the proteins were highly dispersed and homogeneously encapsulated in the
      mesopores of FSM6.2, even at high concentration, although they spontaneously
      aggregated and showed a red shift in solution at the concentration corresponding
      to that in the conjugate. Furthermore, an increase in the amount of sGFP and
      DsRed adsorbed to the pores of FSM6.2 led to a decrease in the distance between
      these proteins, resulting in enhancement of FRET efficiency.

PMID- 18047259
TI  - Nutrition and aging: assessment and treatment of compromised nutritional status
      in frail elderly patients.
AB  - Nutrition is an important determinant of health in persons over the age of 65.
      Malnutrition in the elderly is often underdiagnosed. Careful nutritional
      assessment is necessary for both the successful diagnosis and development of
      comprehensive treatment plans for malnutrition in this population. The purpose of
      this article is to provide clinicians with an educational overview of this
      essential but often underecognized aspect of geriatric assessment. This article
      will review some common issues in nutrition for the elderly in both hospital and
      community settings. The complexity and impact of multiple comorbidities on the
      successful nutritional assessment of elderly patients is highlighted by using
      case scenarios to discuss nutritional issues common to elderly patients and
      nutritional assessment tools. Three case studies provide some context for an
      overview of these issues, which include the physiology of aging, weight loss,
      protein undernutrition, impaired cognition, malnutrition during hospitalization,
      screening procedures, and general dietary recommendations for patients 65 years
      of age and older.

PMID- 18047262
TI  - Scouting human A3 adenosine receptor antagonist binding mode using a molecular
      simplification approach: from triazoloquinoxaline to a pyrimidine skeleton as a
      key study.
AB  - The concept of molecular simplification as a drug design strategy to shorten
      synthetic routes, while keeping or enhancing the biological activity of the lead
      drug, has been applied to design new classes of human A3 adenosine receptor (AR)
      antagonists. Over the past decade, we have focused a part of our research on the
      study of AR antagonists belonging to strictly correlated classes of tricyclic
      compounds. One of these classes is represented by the 2-aryl-1,2,4-triazolo[4,3
      a]quinoxalin-1-one derivatives, either 4-amino or 4-oxo-substituted, which were
      intensively investigated by evaluating the effect of different substituents on
      the 2-phenyl ring and on the 4-amino group. Using an in silico molecular
      simplification approach, a new series of easily synthesizable 2-amino/2
      oxoquinazoline-4-carboxamido derivatives have been discovered, presenting high
      affinity and selectivity against human A3 AR.

PMID- 18047263
TI  - BINOL-amino acid conjugates as triggerable carriers of DNA-targeted potent
      photocytotoxic agents.
AB  - Mild photoactivation of new BINOL-amino acid and -amino ester conjugates
      (BINOLAMs) yielded alkylating and DNA cross-linking agents with high
      photoefficiency and superior cytotoxicity. Detection of the transient
      electrophile, by laser flash photolysis (LFP), suggests that BINOL-quinone
      methides (QMs) are key intermediates in the process. QMs trapping by water,
      monitored in a time-dependent product distribution analysis, demonstrated that
      the phototriggered reactivity of BINOLAMs as bis-alkylating agents is the result
      of a two-step process involving sequential photogeneration of monoalkylating QMs.
      Light activation of the BINOL-L-amino esters produced cytotoxic QMs very
      effective against human tumor LoVo cells with EC50 in the 130-230 nM range.
      Trimethylpsoralen (PS) is about 4 times less potent than our newly tested
      compounds. BINOL-L-proline methyl ester showed notable photoselectivity because
      it displayed cytotoxic effects upon irradiation only and was able to efficiently
      reach the target DNA inside the cells, where it forms both alkylated and cross
      linked species.

PMID- 18047264
TI  - Multi-target-directed drug design strategy: from a dual binding site
      acetylcholinesterase inhibitor to a trifunctional compound against Alzheimer's
      disease.
AB  - A design strategy to convert a dual-binding site AChE inhibitor into triple
      functional compounds with promising in vitro profile against multifactorial
      syndromes, such as Alzheimer's disease, is proposed. The lead compound bis(7)
      tacrine (2) was properly modified to confer to the new molecules the ability of
      chelating metals, involved in the neurodegenerative process. The multifunctional
      compounds show activity against human AChE, are able to inhibit the AChE-induced
      amyloid-beta aggregation, and chelate metals, such as iron and copper.

PMID- 18047266
TI  - A p-[18F]fluoroethoxyphenyl bicyclic nucleoside analogue as a potential positron
      emission tomography imaging agent for varicella-zoster virus thymidine kinase
      gene expression.
AB  - We recently reported a new positron emission tomography (PET) reporter gene,
      namely, varicella-zoster virus thymidine kinase (VZV-tk) in combination, with
      carbon-11 or fluorine-18 labeled m-alkoxyphenyl bicyclic nucleoside analogues
      (BCNAs) as PET reporter probes. We now report the synthesis and evaluation of p
      alkoxyphenyl-BCNA tracers ([11C]-4 and [18F]-5), which are found to be superior
      to the m-alkoxyphenyl-BCNA tracers. In particular, the fluorine-18 labeled tracer
      ([18F]-5, IC50 of 5 is 4.2 microM) shows a higher accumulation in VZV-tk
      expressing cells than the previously reported m-methoxyphenyl BCNA. [11C]-4 and
      [18F]-5 were synthesized by heating the phenol precursor 3 with 11CH 3I and 18FCH
      2CH 2Br, respectively, as alkylating agents. In vitro evaluation of [11C]-4 and
      [18F]-5 in 293T cells showed about 14- and 54-fold higher uptake, respectively,
      into VZV-tk gene-transduced cells compared to control cells. LC-MS analysis
      confirmed the formation of monophosphate derivative of 5 upon catalysis by VZV
      TK. In vivo studies of this new reporter gene/probe system are in progress.

PMID- 18047267
TI  - Design of recombinant antibody microarrays for cell surface membrane proteomics.
AB  - Generating proteomic maps of membrane proteins, common targets for therapeutic
      interventions and disease diagnostics, has turned out to be a major challenge.
      Antibody-based microarrays are among the novel rapidly evolving proteomic
      technologies that may enable global proteome analysis to be performed. Here, we
      have designed the first generation of a scaleable human recombinant scFv antibody
      microarray technology platform for cell surface membrane proteomics as well as
      glycomics targeting intact cells. The results showed that rapid and multiplexed
      profiling of the cell surface proteome (and glycome) could be performed in a
      highly specific and sensitive manner and that differential expression patterns
      due to external stimuli could be monitored.

PMID- 18047268
TI  - Rapid and reliable peptide de novo sequencing facilitated by microfluidic chip
      based Edman degradation.
AB  - This paper expands the application of the newly developed highly sensitive
      microfluidic chip-based Edman degradation system. Comparison between the MS/MS
      spectra of a native peptide and its N-terminus truncated counterpart after
      carrying out one cycle of Edman degradation in a microfluidic chip can not only
      provide N-terminal residue information, but also facilitate the identification of
      different series of fragment ions. Manual peptide sequencing is more feasible and
      rapid using this method as demonstrated with three peptide examples including one
      neuropeptide. Furthermore, two cycles of Edman degradation allow the
      determination of the exact value of b 2 ion of the intact peptide, which can
      serve as an internal calibrant to increase the mass accuracy of the MS/MS
      spectrum.

PMID- 18047269
TI  - Specific on-plate enrichment of phosphorylated peptides for direct MALDI-TOF MS
      analysis.
AB  - An on-plate specific enrichment method is presented for the direct analysis of
      peptides phosphorylation. An array of sintered TiO 2 nanoparticle spots was
      prepared on a stainless steel plate to provide porous substrate with a very large
      specific surface and durable functions. These spots were used to selectively
      capture phosphorylated peptides from peptide mixtures, and the immobilized
      phosphopeptides could then be analyzed directly by MALDI MS after washing away
      the nonphosphorylated peptides. beta-Casein and protein mixtures were employed as
      model samples to investigate the selection efficiency. In this strategy, the
      steps of phosphopeptide capture, purification, and subsequent mass spectrometry
      analysis are all successfully accomplished on a single target plate, which
      greatly reduces sample loss and simplifies analytical procedures. The low
      detection limit, small sample size, and rapid selective entrapment show that this
      on-plate strategy is promising for online enrichment of phosphopeptides, which is
      essential for the analysis of minute amount of samples in high-throughput
      proteome research.

PMID- 18047270
TI  - Quantitation by isobaric labeling: applications to glycomics.
AB  - The study of glycosylation patterns (glycomics) in biological samples is an
      emerging field that can provide key insights into cell development and pathology.
      A current challenge in the field of glycomics is to determine how to quantify
      changes in glycan expression between different cells, tissues, or biological
      fluids. Here we describe a novel strategy, quantitation by isobaric labeling
      (QUIBL), to facilitate comparative glycomics. Permethylation of a glycan with
      (13)CH 3I or (12)CH 2DI generates a pair of isobaric derivatives, which have the
      same nominal mass. However, each methylation site introduces a mass difference of
      0.002922 Da. As glycans have multiple methylation sites, the total mass
      difference for the isobaric pair allows separation and quantitation at a
      resolution of approximately 30000 m/Delta m. N-Linked oligosaccharides from a
      standard glycoprotein and human serum were used to demonstrate that QUIBL
      facilitates relative quantitation over a linear dynamic range of 2 orders of
      magnitude and permits the relative quantitation of isomeric glycans. We applied
      QUIBL to quantitate glycomic changes associated with the differentiation of
      murine embryonic stem cells to embryoid bodies.

PMID- 18047271
TI  - Analyzing large-scale proteomics projects with latent semantic indexing.
AB  - Since the advent of public data repositories for proteomics data, readily
      accessible results from high-throughput experiments have been accumulating
      steadily. Several large-scale projects in particular have contributed
      substantially to the amount of identifications available to the community.
      Despite the considerable body of information amassed, very few successful
      analyses have been performed and published on this data, leveling off the
      ultimate value of these projects far below their potential. A prominent reason
      published proteomics data is seldom reanalyzed lies in the heterogeneous nature
      of the original sample collection and the subsequent data recording and
      processing. To illustrate that at least part of this heterogeneity can be
      compensated for, we here apply a latent semantic analysis to the data contributed
      by the Human Proteome Organization's Plasma Proteome Project (HUPO PPP).
      Interestingly, despite the broad spectrum of instruments and methodologies
      applied in the HUPO PPP, our analysis reveals several obvious patterns that can
      be used to formulate concrete recommendations for optimizing proteomics project
      planning as well as the choice of technologies used in future experiments. It is
      clear from these results that the analysis of large bodies of publicly available
      proteomics data by noise-tolerant algorithms such as the latent semantic analysis
      holds great promise and is currently underexploited.

PMID- 18047272
TI  - Identification of mouse embryonic stem cell-associated proteins.
AB  - Over the past few years, there has been a growing interest in discovering the
      molecular mechanisms controlling embryonic stem cells' (ESCs) proliferation and
      differentiation. Proteome analysis has proven to be an effective approach to
      comprehensively unravel the regulatory network of differentiation. We applied a
      two-dimensional electrophoresis based proteomic approach followed by mass
      spectrometry to analyze the proteome of two mouse ESC lines, Royan B1 and D3, at
      0, 6, and 16 days after differentiation initiation. Out of 97 ESC-associated
      proteins commonly expressed in two ESC lines, 72 proteins were identified using
      MALDI TOF-TOF mass spectrometry analysis. The expression pattern of four down
      regulated proteins including Hspd1, Hspa8, beta-Actin, and Tpt1 were further
      confirmed by Western blot and immunofluorescence analyses in Royan B1 and D3 as
      well as two other mouse ESC lines, Royan C1 and Royan C4. Differential mRNA
      expression analysis of 20 genes using quantitative real-time reverse
      transcription PCR revealed a low correlation between mRNA and protein levels
      during differentiation. We also observed that the mRNA level of Tpt1 increased
      significantly in differentiating cells, whereas its protein level decreased.
      Several novel ESC-associated proteins have been presented in this study which
      warrants further investigation with respect to the etiology of stemness.

PMID- 18047273
TI  - Proteomic analysis of human follicular fluid using an alternative bottom-up
      approach.
AB  - Human follicular fluid (hFF) is the in vivo environment of oocytes during
      follicular maturation in the ovaries. It contains a huge variety of compounds
      such as, e.g., proteins that might play an important role in follicular
      development and oocyte growth. Previous proteomic studies on follicular fluid
      have isolated and already identified a certain number of proteins. Nevertheless,
      only a small part of proteins present in follicular fluid have been covered so
      far and a large number have still not been identified. Therefore, the need for
      new, more resolving, and sensitive approaches in proteome research is evident. We
      utilized a proteomic setup based on in solution isoelectric focusing (IEF) and
      reversed-phase nanoliquid chromatography coupled to matrix-assisted laser
      desorption/ionization time-of-flight tandem mass spectrometry (nano-LC MALDI
      TOF/TOF MS) for in depth protein analysis of human follicular fluid samples of
      patients undergoing controlled ovarian hyper stimulation (COH) for in vitro
      fertilization therapy (IVF). This approach led to the significant identification
      of 69 proteins, where 32 have not been reported before to be found in human
      follicular fluid with proteomic methods. Among these findings, at least two
      relevant compounds essentially involved in hormone secretion regulation during
      the folliculogenetic process were identified: sex hormone binding globulin (SHBG)
      and inhibin A (INHA). To confirm these results, both proteins were further
      validated by immunoassays.

PMID- 18047274
TI  - Flexible microarray construction and fast DNA hybridization conducted on a
      microfluidic chip for greenhouse plant fungal pathogen detection.
AB  - This study employed a microfluidic method in which probe creation does not
      require pin-spotting and fast hybridization is conducted on the same microarray
      chip for the detection of three greenhouse pathogens ( Botrytis cinerea,
      Didymella bryoniae, and Botrytis squamosa). In this method, 16 oligonucleotide
      probe line arrays were created on a glass substrate by a microfluidic printing
      method. Then, low amounts of the DNA samples (1 fmol of oligonucelotides or 1.4
      ng of PCR products) were introduced into the microchannels that were orthogonal
      to these probe lines. The hybridizations of 16 samples (21-mer complementary
      oligonuleotides and approximately 260 bp PCR products) were fulfilled at the
      channel-probe line intersections and in a short time (minutes). The optimization
      of probe immobilization and sample hybridization are described in detail. The
      method successfully detected and discriminated between two 260 bp PCR products
      with a one-base-pair difference from closely related greenhouse plant fungal
      pathogens (B. cinerea and B. squamosa).

PMID- 18047275
TI  - Molar absorptivities and reducing capacity of pyranoanthocyanins and other
      anthocyanins.
AB  - To improve accuracy in the determination of anthocyanin purity and succeeding
      antioxidant capacity, 1H and 13C nuclear magnetic resonance spectroscopy have
      been combined with high-performance liquid chromatography (HPLC) equipped with a
      diode array detector and UV-vis spectroscopy in the analysis of anthocyanidin 3
      glycosides and 5-carboxypyranoanthocyanidin 3-glycosides. The molar absoptivity
      (epsilon) values were found to be relatively similar, in contrast to previously
      reported literature values, and the average epsilon values for both anthocyanidin
      3-monoglycosides and 5-carboxypyranoanthocyanidin 3-glycosides were proposed to
      be 22,000 and 23,000 in acidified aqueous and methanolic solutions, respectively.
      To assess the influence of structure on the potential antioxidant capacity of
      anthocyanins, the 3-glucosides of pelargonidin (1), cyanidin (2), peonidin (3),
      delphinidin (4), petunidin (5), malvidin (6), 5-carboxypyranopelargonidin (8), 5
      carboxypyranocyanidin (9), 5-carboxypyranodelphinidin (11), 5
      carboxypyranopetunidin (12), and 5-carboxypyranomalvidin (13) and the 3
      galactosides of cyanidin (7) and 5-carboxypyranocyanidin (14) were examined by a
      ferric ion reducing antioxidant power (FRAP) assay. The reducing capacities of
      the individual anthocyanins were in the range of 0.9-5.2 micromol of Trolox
      equivalents/micromol. The two 5-carboxypyranoanthocyanins 11 and 9 and the four
      common anthocyanins 2, 4, 7, and 14, all possessing pyrogallol or catechol type
      of B rings, showed the highest antioxidant capacity measured by FRAP. However,
      the inclusion of the 5-hydroxyl in the D ring and just one oxygen substituent on
      the B ring in 8 diminished the reducing capacity considerably. Correspondingly,
      electrochemical behavior of 5-carboxypyranoanthocyanidin 3-glucosides and
      anthocyanidin 3-glucosides was derived using HPLC coupled to a coulometric array
      detector set from 100 to 800 mV in increments of 100 mV. The relative order of
      the reducing capacity of the various 5-carboxypyranoanthocyanidin 3-glucosides
      and anthocyanidin 3-glucosides were nearly alike, whether determined by
      coulometric array detection or FRAP.

PMID- 18047276
TI  - Aging effects and grape variety dependence on the content of sulfur volatiles in
      wine.
AB  - Thirteen sulfur compounds (boiling points from 35 to 231 degrees C), usually
      considered as possible off-flavoring volatiles, were quantified by a concurrent
      headspace-solid phase microextraction method coupled with gas chromatography-mass
      spectrometry (HS-SPME/GC-MS) on 80 not off-flavoring wines of four varieties
      (Merlot, Marzemino, and Teroldego as red wines and Chardonnay as a white one) and
      of five vintages produced in the North Italian Trentino region. The results of
      the research, the first Italian data-bank per variety on such volatiles, allow us
      to make a comparison with the data of other winegrowing areas, to investigate the
      aging effect on the considered volatiles, and, finally, to try a variety
      discrimination using statistical procedures. Dimethyl sulfide, 3-(methylthio)-1
      propanol, diethyl sulfide, and diethyl disulfide were found to increase with time
      whereas 2-mercaptoethanol and ethylmercaptan showed a decreasing trend.
      Furthermore, the concentration of several compounds was found to be dependent on
      the variety. For instance, sulfide, disulfides, benzothiazole, and thioalcohols
      are at higher levels in Merlot wines, whereas thiols and thioacetates are more
      abundant in Marzemino and Teroldego wines. Chardonnay products, well apart from
      the other wines, are the poorest in 3-(methylthio)-1-propanol and rather rich in
      dimethyl disulfide and in diethyl disulfide, mostly in the aged wines. Applying
      the principal component analysis to the data, it was possible to demonstrate that
      Chardonnay and Merlot wines are well-discriminated from the Italian native
      varietal wines, which on their turn are only partially distinguishable among
      them. A contribution of these compounds to the variety characteristics of wine is
      reasonable.

PMID- 18047277
TI  - Water absorption of freeze-dried meat at different water activities: a
      multianalytical approach using sorption isotherm, differential scanning
      calorimetry, and nuclear magnetic resonance.
AB  - Hydration of freeze-dried chicken breast meat was followed in the water activity
      range of aw=0.12-0.99 by a multianalytical approach comprising of sorption
      isotherm, differential scanning calorimetry (DSC), and nuclear magnetic resonance
      (NMR). The amount of frozen water and the shape of the T2-relaxogram were
      evaluated at each water content by DSC and NMR, respectively. Data revealed an
      agreement between sorption isotherm and DSC experiments about the onset of bulk
      water (aw=0.83-0.86), and NMR detected mobile water starting at aw=0.75. The
      origin of the short-transverse relaxation time part of the meat NMR signal was
      also reinvestigated through deuteration experiments and proposed to arise from
      protons belonging to plasticized matrix structures. It is proved both by D2O
      experiments and by gravimetry that the extra protons not contributing to the
      water content in the NMR experiments are about 6.4% of the total proton NMR CPMG
      signal of meat.

PMID- 18047278
TI  - Vascular effects, angiotensin I-converting enzyme (ACE)-inhibitory activity, and
      antihypertensive properties of peptides derived from egg white.
AB  - In this study, we have identified novel antihypertensive peptides derived from
      egg-white proteins. The sequences YRGGLEPINF and ESIINF produced an acute blood
      pressure-lowering effect in spontaneously hypertensive rats upon a single oral
      administration. Our results suggest that the antihypertensive action could be
      attributed to a vascular-relaxing mechanism that would occur in vivo
      independently of angiotensin I-converting enzyme (ACE) inhibition, because
      neither these peptides nor their main digestion fragments, except for the
      dipeptide YR, acted as ACE inhibitors in vitro. The vasodilator and
      antihypertensive activity of the sequences ESI and NF would explain the blood
      pressure-lowering effect of ESIINF. With regard to YRGGLEPINF, in addition to NF,
      YR appeared as the main fragment responsible for its activity. The dipeptide YR,
      named kyotorphin and previously identified as an endogenous analgesic
      neuropeptide in the central nervous system, showed strong vasodilator and
      antihypertensive properties. The structure-activity features of the vasodilator
      peptides are discussed.

PMID- 18047279
TI  - Impact of casein gel microstructure on self-diffusion coefficient of molecular
      probes measured by 1H PFG-NMR.
AB  - The translational dynamics of poly(ethylene glycol) (PEG) polymers with molecular
      weights (Mw) varying from 6x10(2) to 5x10(5) were investigated by pulsed field
      gradient NMR in casein suspensions and in gels induced by acidification, enzyme
      action, and a combination of both. For molecules with Mw<or=1020, the diffusion
      was only dependent on the casein concentration whatever the molecular weight of
      the probe or the sample studied. However, for PEG with Mw>or=8000, there was
      strong dependence of diffusion on PEG size and on the casein network structure as
      revealed by scanning electron microscopy images. The diffusion coefficients of
      the two largest PEGs were increased after coagulation by amounts that depended on
      the internal structure of the gel. In addition, the 527,000 g/mol PEG was found
      to deviate from Gaussian diffusion behavior to greater or lesser extents
      according to the casein concentration and the sample microstructure. The results
      are discussed in terms of network rearrangements.

PMID- 18047280
TI  - A simple and rapid approach for removing citrinin while retaining monacolin K in
      red mold rice.
AB  - Monascus species-fermented red mold rice (RMR) has been regarded as a popular
      hypolipidemic functional food because it contains monacolin K, an inhibitor of de
      novo cholesterol synthesis. However, the safety of RMR is always an issue because
      citrinin is present in RMR and is reported to be hepatotoxic and nephrotoxic. The
      present study was therefore to develop a postprocess to remove citrinin yet
      retain monacoln K in the RMR preparation. We found that phosphate-ethanol
      extraction was effective for the removal citrinin, yet it could retain monacolin
      K, because the former was more hydrophilic than the latter in phosphate-ethanol
      solution. Ethanol, phosphate, and extraction time were optimized as factors of
      response surface methodology (RSM). It was found that the optimal RSM condition
      was 45% ethanol, 1.5% phosphate, and extraction for 70 min. Under this optimal
      condition, 91.6% citrinin was removed and 79.5% monacolin K was retained in the
      final RMR.

PMID- 18047281
TI  - Retention of provitamin A carotenoids in high beta-carotene maize (Zea mays)
      during traditional African household processing.
AB  - High beta-carotene maize, biofortified with beta-carotene through plant breeding,
      is being developed as a cost-effective, sustainable agronomic approach to
      alleviating the problem of vitamin A deficiency in Africa. We used high beta
      carotene maize (10.49+/-0.16 microg beta-carotene/g) to prepare traditional maize
      porridges and compared the carotenoid contents in the following: (1) whole
      kernels; (2) wet milled flour; (3) wet milled flour, fermented; (4) wet milled
      flour, cooked; (5) wet milled flour, fermented and cooked. The cumulative losses
      of beta-carotene in the final, cooked products were 24.5% (95% CI 22.8-26.2%) and
      24.8% (95% CI 23.1-26.5%), for the fermented and unfermented porridges,
      respectively. Thus, fermentation, a traditional technology with documented
      nutritional and other health benefits, does not adversely affect the retention of
      beta-carotene in porridges prepared with high beta-carotene maize. The relatively
      good retention of beta-carotene during traditional maize processing provides
      additional experimental support for the feasibility of maize biofortification as
      a means to alleviate vitamin A deficiency.

PMID- 18047282
TI  - Infrared imaging of sunflower and maize root anatomy.
AB  - Synchrotron radiation infrared microspectroscopy (SR-IMS) permits the direct
      analysis of plant cell-wall architecture at the cellular level in situ, combining
      spatially localized information and chemical information from IR absorbances to
      produce a chemical map that can be linked to a particular morphology or
      functional group. This study demonstrated the use of SR-IMS to probe biopolymers,
      such as cellulose, lignin, and proteins, in the root tissue of hydroponically
      grown sunflower and maize plants. Principal components analysis (PCA) was
      employed to reveal the major spectral variance between maize and sunflower plant
      tissues. The use of PCA showed distinct separation of maize and sunflower samples
      using the IR spectra of the epidermis and xylem. The infrared band at 1635 cm(
      1), representing hydrocinnamic acid in (H type) lignin, provided a conclusive
      means of distinguishing between maize and sunflower plant tissues.

PMID- 18047283
TI  - Effect of heat damage in an autoclave on the reactive lysine contents of soy
      products and corn distillers dried grains with solubles. Use of the results to
      check on lysine damage in common qualities of these ingredients.
AB  - The suitability of the homoarginine reaction for determining the reactive lysine
      in soy products and corn distillers dried grain with solubles (DDGS) was tested.
      For this purpose, some batches were subjected to deliberate heat damage for up to
      30 min in an autoclave with 135 degrees C hot steam, and the samples were
      analyzed for total lysine and reactive lysine. In addition, 84 samples of common
      soy and 80 samples of corn DDGS were tested for their content of total and
      reactive lysine, and the contents were compared with those of the autoclave
      tests. For soy products conclusive results were obtained. In the case of heat
      treatment, both total lysine and reactive lysine decrease, but the latter is
      clearly a more sensitive indicator of lysine damage. Most normal products are
      quite similar, with toasting-induced damage to reactive lysine of ca. 15%
      compared to untoasted beans. The cause of the constantly occurring residual
      lysine after guanidination and the poorer reaction balance in the case of damage
      were explained. For common DDGS samples, however, less favorable results were
      obtained. Reactive and total lysine decreased almost in parallel due to heat
      damage, showing a great gap between them. Results showed indeed that variation of
      total and reactive lysine in DDGS is high, proving that its production conditions
      are not yet optimal for a feed ingredient.

PMID- 18047284
TI  - Polyphenols are intensively metabolized in the human gastrointestinal tract after
      apple juice consumption.
AB  - Polyphenols are secondary plant compounds showing anticarcinogenic effects both
      in vitro and in animal experiments and may thus reduce the risk of colorectal
      cancer in man. The identification of polyphenol metabolites formed via their
      passage through the small intestine of healthy ileostomy subjects after apple
      juice consumption is presented. Identification and quantification of polyphenols
      and their metabolites were performed using HPLC-DAD as well as HPLC-ESI-MS/MS.
      Total procyanidin content (TPA) was measured, and additionally the mean degree of
      polymerization (DPm) of the procyanidins was determined in the apple juice and
      ileostomy effluents. As products of polyphenol metabolism, D-(-)-quinic acid and
      methyl esters of caffeic acid and p-coumaric acid are liberated from the
      corresponding hydroxycinnamic acid esters. 1-Caffeoylquinic acid and 3
      caffeoylquinic acid were determined as products of isomerization. Phloretin 2'-O
      glucoside (phloridzin) and phloretin 2'-O-xyloglucoside were metabolized into the
      corresponding aglycons phloretin and phloretin 2'-O-glucuronide and all were
      found in the ileostomy effluent. Ninety percent of the consumed procyanidins were
      recovered in the ileostomy effluent and therefore would reach the colon under
      physiologic circumstances. The DP m was reduced (DP m of apple juice=5.7) and
      varied depending on the time point of excretion. The gastrointestinal passage
      seems to play an important role in the colonic availability of apple polyphenols.

PMID- 18047285
TI  - Self-assembly and adhesion of DOPA-modified methacrylic triblock hydrogels.
AB  - Marine mussels anchor to a variety of surfaces by secreting liquid proteins that
      harden and form water-resistant bonds to a variety of surfaces. Studies have
      revealed that these mussel adhesive proteins contain an unusual amino acid, 3,4
      dihydroxy-L-phenylalanine (DOPA), which is believed to be responsible for the
      cohesive and adhesive properties of these proteins. To separate the cohesive and
      adhesive roles of DOPA, we incorporated DOPA into the midblock of poly(methyl
      methacrylate)-poly(methacrylic acid)-poly(methyl methacrylate) (PMMA-PMAA-PMMA)
      triblock copolymers. Self-assembled hydrogels were obtained by exposing triblock
      copolymer solutions in dimethyl sulfoxide to water vapor. As water diffused into
      the solution, the hydrophobic end blocks formed aggregates that were bridged by
      the water-soluble midblocks. Strong hydrogels were formed with polymer weight
      fractions between 0.01 and 0.4 and with shear moduli between 1 and 5 kPa. The
      adhesive properties of the hydrogels on TiO2 surfaces were investigated by
      indentation with a flat-ended cylindrical punch. At pH values of 6 and 7.4, the
      fully protonated DOPA groups were highly adhesive to the TiO2 surfaces, giving
      values of approximately equal to 2 J/m2 for the interfacial fracture energy,
      which we believe corresponds to the cohesive fracture energy of the hydrogel. At
      these pH values, the DOPA groups are hydrophobic and have a tendency to
      aggregate, so contact times of 10 or 20 min are required for these high values of
      the interfacial strength to be observed. At a pH of 10, the DOPA groups were
      hydrophilic and highly swellable, but less adhesive gels were formed. Oxidation
      of DOPA groups, a process that is greatly accelerated at a pH of 10, decreased
      the adhesive performance of the hydrogels even further.

PMID- 18047286
TI  - Synthesis and characterization of radiopaque iodine-containing degradable PVA
      hydrogels.
AB  - Poly (vinyl alcohol) (PVA) hydrogels are highly attractive for biomedical
      applications, especially for controlled release of drugs and proteins. Recently,
      degradable PVA hydrogels have been described, having the advantage that the
      material disappears over time from the implantation site. Herein, we report the
      synthesis of radiopaque degradable PVA, which gives a further advantage that the
      position of the hydrogel can precisely be determined by X-ray fluoroscopy.
      Radiopacity has been introduced by replacing 0.5% of the pendent alcohol groups
      on the PVA with 4-iodobenzoylchloride. This level of substitution rendered the
      polymer adequately radiopaque. The subsequent modification of 0.8% of the pendent
      hydroxyl groups with an ester acrylate functional group allowed for cross-linking
      of the macromers. The radiopaque hydrogels degraded over a time span of 140 days.
      Rheology data suggested that the macromer solutions were appropriate for
      injection.

PMID- 18047287
TI  - Scattering and turbidity study of the dissociation of casein by calcium
      chelation.
AB  - The dissociation of casein was studied after addition of polyphosphate that leads
      to calcium chelation, using light and X-ray scattering and turbidimetry. It is
      shown that the dissociation is a cooperative process; that is, a casein complex
      is either completely dissociated or remains largely intact. A systematic study
      was done of the dependence of the rate and extent of dissociation on the
      polyphosphate concentration and was found to be determined by the ratio between
      casein and polyphosphate. The structures of the casein complex and the small
      micellar particles formed after dissociation were compared. Additional
      experiments with a different chelatant (EDTA) gave similar results.

PMID- 18047288
TI  - New amphiphilic lactic acid oligomer-hyaluronan conjugates: synthesis and
      physicochemical characterization.
AB  - The "grafting onto" strategy was used to conjugate DL-lactic acid oligomers (OLA)
      to hyaluronan (HA) for the sake of developing novel degradable HA-based self
      assembling polymeric systems. Grafting was achieved by reacting COCl-terminated
      OLA with cetyltrimethylammonium hyaluronate (CTA-HA) in dimethyl sulfoxide
      (DMSO). The resulting CTA-HAOLA conjugates were purified and turned to sodium
      form (Na-HAOLA) by dissolution in a phosphate buffer-DMSO mixture and successive
      dialyses against DMSO, ethanol, and water. In contrast, when the same protocol
      was applied to CTA-HAOLA, phase separation with gel formation was observed. The
      solution phase was composed of Na-HAOLA whereas the gel phase was made of mixed
      CTA-Na-HAOLA salt with ca. 25% of the carboxyl groups neutralized by CTA.
      Gelation was assigned to intramolecular hydrophobic associations between OLA and
      cetyl alkyl chains that complemented electrostatic interactions between CTA and
      HA COO- groups synergistically. Therefore, the corresponding stabilized CTA ions
      required more drastic conditions to be released. Under the selected dialysis
      conditions, the CTA-Na-HAOLA gels formed tiny tubes. Na-HAOLA and CTA-Na-HAOLA
      were characterized by FTIR, one-dimensional 1H and two-dimensional 1H NMR. The
      extent of grafting was ca. 5% per disaccharidic repeating unit, regardless of the
      molecular weight, as determined by NMR and capillary zone electrophoresis.
      Amphiphilic Na-HAOLA molecules were aggregated and formed spherical species in
      water according to size exclusion chromatography combined with multiangle laser
      light scattering detection. The critical aggregation concentration ranged between
      0.2 and 0.35% (w/v), depending of the molecular weight of the parent hyaluronan.

PMID- 18047289
TI  - Micelles based on biodegradable poly(L-glutamic acid)-b-polylactide with
      paramagnetic Gd ions chelated to the shell layer as a potential nanoscale MRI
      visible delivery system.
AB  - There is much interest in the development of a nanoscale drug delivery system
      with MRI visibility to optimize the delivery efficiency and therapeutic efficacy
      under image guidance. Here we report on the successful fabrication of nanoscale
      micelles based on biodegradable poly( L-glutamic acid)- b-polylactide (PG- b-PLA)
      block copolymer with paramagnetic Gd3+ ions chelated to their shell. PG- b-PLA
      was synthesized by sequential polymerization reactions: anionic polymerization of
      L-lactide followed by ring-opening polymerization of benzyl glutamate N
      carboxylic anhydride. The metal chelator p
      aminobenzyldiethylenetriaminepenta(acetic acid) (DTPA) was readily conjugated to
      the side chain carboxylic acids of poly( L-glutamic acid). The resulting
      copolymer formed spherical micelles in aqueous solution with an average diameter
      of 230 nm at pH 7.4. The size of PG(DTPA)- b-PLA micelles decreased with
      increasing pH value. DTPA-Gd chelated to the shell layer of the micelles
      exhibited significantly higher spin-lattice relaxivity (r1) than a small
      molecular-weight MRI contrast agent, indicating that water molecules could
      readily access the Gd ions in the micelles. Because of the presence of multiple
      carboxylic acid functional groups in the shell layer, polymeric micelles based on
      biodegradable PG(DTPA-Gd)- b-PLA may be a suitable platform for the development
      of MRI-visible, targeted nanoscale drug delivery systems.

PMID- 18047290
TI  - Influence of enzymatic specificity on the behavior of ephemeral gels.
AB  - Ephemeral gels, called Enzgels, successively undergo sol-gel and then gel-sol
      transition under the action of two antagonistic enzymes, transglutaminase and
      protease. Molecular and macroscopic properties of Enzgels are directly dependent
      on the enzymatic activities and their ratios. This work studies the
      characteristics of Enzgels according to the specificity of three different
      proteases: thermolysin, trypsin, and collagenase. The experiments are conducted
      using three types of gelatin networks, one created only by triple helices, one
      only by covalent bonds, and the last network by both triple helices and covalent
      bonds. Rheology and polarimetry measurements show that the evolution of Enzgels
      is directly dependent on the specificity of the protease used. Moreover, gelatin
      network conformation has different influences according to this proteolytic
      specificity. Collagenase is not very sensitive to gelatin conformation, whereas
      trypsin is very limited by the presence of covalent bonds. This study
      considerably expands the knowledge of Enzgel properties.

PMID- 18047291
TI  - Design and biophysical characterization of novel polycationic epsilon-peptides
      for DNA compaction and delivery.
AB  - Design and solid-phase synthesis of novel and chemically defined linear and
      branched -oligo( l-lysines) (denoted -K n, where n is the number of lysine
      residues) and their alpha-substituted homologues (epsilon-(R)K10, epsilon-(Y)K10,
      epsilon-(L)K10, epsilon-(YR)K10, and epsilon-(LYR)K10) for DNA compaction and
      delivery are reported. The ability to condense viral (T2 and T4) and plasmid DNA
      as well as the size of -peptide DNA complexes under different conditions was
      investigated with static and dynamic light scattering, isothermal titration
      calorimetry, and fluorescence microscopy. Nanoparticle diameters varied from 100
      to 150 and 375 to 550 nm for plasmid and T4 DNA peptide complexes, respectively.
      Smaller sizes were observed for oligo(L-lysines) compared to alpha-poly( L
      lysine). The linear -oligo-lysines are less toxic and epsilon-(LYR)K10 showed
      higher transfection efficiency in HeLa cells than corresponding controls. The
      results also demonstrate that with a branched design having pendent groups of
      short alpha-oligopeptides, improved transfection can be achieved. This study
      supports the hypothesis that available alpha-oligolysine derived systems would
      potentially have more favorable delivery properties if they are based instead on
      epsilon-oligo( L-lysines). The flexible design and unambiguous synthesis that
      enables variation of pendent groups holds promise for optimization of such 
      peptides to achieve improved DNA compaction and delivery.

PMID- 18047292
TI  - Halichonadin E, a dimeric sesquiterpenoid from the sponge Halichondria sp.
AB  - A new dimeric sesquiterpenoid with eudesmane and aromadendrane skeletons linked
      through a urea fragment, halichonadin E ( 1), was isolated from a marine sponge
      Halichondria sp., and the gross structure and relative configuration of 1 were
      elucidated on the basis of spectroscopic data. Halichonadin E ( 1) is the first
      hetero-dimeric sesquiterpenoid with eudesmane and aromadendrane skeletons linked
      through a urea fragment.

PMID- 18047293
TI  - Lipoperoxidation and cyclooxygenase enzyme inhibitory piperidine alkaloids from
      Cassia spectabilis green fruits.
AB  - Phytochemical work in the search for bioactive metabolites from the methanolic
      extract of Senna spectabilis green fruits led to the isolation of a new
      piperidine alkaloid, (+)-3- O-feruloylcassine ( 1), in addition to the known (-)
      spectaline ( 2) and (-)-3- O-acetylspectaline ( 3). The isolates were submitted
      to in vitro evaluation of lipoperoxidation (LPO) and cyclooxygenase enzymes (COX
      1 and -2) inhibitory properties and showed moderate antioxidant activities (40
      70%) at 100 ppm when compared to commercial standards BHT and vitamin E and
      moderate inhibition of COX-1 (ca . 40%) and marginal inhibition of COX-2 enzymes
      (<10%) at 100 ppm when compared to nonsteroidal anti-inflammatory drugs (NSAIDs)
      aspirin, rofecoxib, and celecoxib, respectively.

PMID- 18047294
TI  - Isoflavone tetraglycosides from Sophora japonica Leaves.
AB  - Two new isoflavone tetraglycosides ( 1 and 2) and six known compounds were
      isolated from the leaves of Sophora japonica. The new glycosides are genistein 7-
      O-beta- d-glucopyranoside-4'- O-(6'''- O-alpha- l-rhamnopyranosyl)-beta
      sophoroside ( 1) and genistein 7- O-alpha- l-rhamnopyranoside-4'- O-(6'''- O
      alpha- l-rhamnopyranosyl)-beta-sophoroside ( 2). The structures of compounds 1
      and 2 were established primarily by NMR experiments and chemical methods, and
      they are the first reported naturally occurring isoflavone glycosides with four
      attached sugar residues.

PMID- 18047295
TI  - Kinetics of hypobromous acid-mediated oxidation of lipid components and
      antioxidants.
AB  - Hypohalous acids are generated from the oxidation of halide ions by
      myeloperoxidase and eosinophil peroxidase in the presence of H2O2. These oxidants
      are potent antibacterial agents, but excessive production can result in host
      tissue damage, with this implicated in a number of human pathologies. Rate
      constants for HOCl with lipid components and antioxidants have been established.
      Here, the corresponding reactions of HOBr have been examined to determine whether
      this species shows similar reactivity. The second-order rate constants for the
      reaction of HOBr with 3-pentenoic acid and sorbate, models of unsaturated lipids,
      are 1.1x10(4) and 1.3x10(3) M(-1) s(-1), respectively, while those for reaction
      of HOBr with phosphoryl-serine and phosphoryl-ethanolamine are ca. 10(6) M(-1) s(
      1). The second-order rate constants (M(-1) s(-1)) for reactions of HOBr with
      Trolox (6.4x10(4)), hydroquinone (2.4x10(5)), and ubiquinol-0 (2.5x10(6)) were
      determined, as models of the lipid-soluble antioxidants, alpha-tocopherol, and
      ubiquinol-10; all of these rate constants are ca. 50-2000-fold greater than for
      HOCl. In contrast, the second-order rate constants for the reaction of HOBr with
      the water-soluble antioxidants, ascorbate and urate, are ca. 10(6) M(-1) s(-1)
      and closer in magnitude to those for HOCl. Kinetic models have been developed to
      predict the sites of HOBr attack on low-density lipoproteins. The data obtained
      indicate that HOBr reacts to a much greater extent with fatty acid side chains
      and lipid-soluble antioxidants than HOCl; this has important implications for
      HOBr-mediated damage to cells and lipoproteins.

PMID- 18047297
TI  - Evaluation of multitransducer arrays for the determination of organic vapor
      mixtures.
AB  - A study of vapor recognition and quantification by polymer-coated multitransducer
      (MT) arrays is described. The primary data set consists of experimentally derived
      sensitivities for 11 organic vapors obtained from 15 microsensors comprising five
      cantilever, capacitor, and calorimeter devices coated with five different
      sorptive-polymer films. These are used in Monte Carlo simulations coupled with
      principal component regression models to assess expected performance. Recognition
      rates for individual vapors and for vapor mixtures of up to four components are
      estimated for single-transducer (ST) arrays of up to five sensors and MT arrays
      of up to 15 sensors. Recognition rates are not significantly improved by
      including more than five sensors in an MT array for any specific analysis,
      regardless of difficulty. Optimal MT arrays consistently outperform optimal ST
      arrays of similar size, and with judiciously selected 5-sensor MT arrays, one
      third of all possible ternary vapor mixtures are reliably discriminated from
      their individual components and binary component mixtures, whereas none are
      reliably determined with any of the ST arrays. Quaternary mixtures could not be
      analyzed effectively with any of the arrays. A "universal" MT array consisting of
      eight sensors is defined, which provides the best possible performance for all
      analytical scenarios. Accurate quantification is predicted for correctly
      identified vapors.

PMID- 18047299
TI  - Trapping and release of CO2 guest molecules by amorphous ice.
AB  - Interactions of 13CO2 guest molecules with vapor-deposited porous H2O ices have
      been examined using temperature-programmed desorption (TPD) and Fourier transform
      infrared (FTIR) techniques. Specifically, the trapping and release of 13CO2 by
      amorphous solid water (ASW) has been studied. The use of 13CO2 eliminates
      problems with background CO2. Samples were prepared by (i) depositing 13CO2 on
      top of ASW, (ii) depositing 13CO2 underneath ASW, and (iii) codepositing 13CO2
      and H2O during ASW formation. Some of the deposited 13CO2 becomes trapped when
      the ice film is annealed. The amount of 13CO2 trapped in the film depends on the
      deposition method. The release of trapped molecules occurs in two stages. The
      majority of the trapped 13CO2 escapes during the ASW-to-cubic ice phase
      transition at 165 K, and the rest desorbs together with the cubic ice film at 185
      K. We speculate that the presence of 13CO2 at temperatures up to 185 K is due to
      13CO2 that is trapped in cavities within the ASW film. These cavities are similar
      to ones that trap the 13CO2 that is released during crystallization. The
      difference is that 13CO2 that remains at temperatures up to 185 K does not have
      access to escape pathways to the surface during crystallization.

PMID- 18047298
TI  - Non-nearest-neighbor dependence of the stability for RNA bulge loops based on the
      complete set of group I single-nucleotide bulge loops.
AB  - Fifty-nine RNA duplexes containing single-nucleotide bulge loops were optically
      melted in 1 M NaCl, and the thermodynamic parameters DeltaH degrees, DeltaS
      degrees, DeltaG 37 degrees, and TM for each sequence were determined. Sequences
      from this study were combined with sequences from previous studies [Longfellow,
      C. E., et al. (1990) Biochemistry 29, 278-285; Znosko, B. M., et al. (2002)
      Biochemistry 41, 10406-10417], thus examining all possible group I single
      nucleotide bulge loop and nearest-neighbor sequence combinations. The free energy
      increments at 37 degrees C for the introduction of a group I single-nucleotide
      bulge loop range between 1.3 and 5.2 kcal/mol. The combined data were used to
      develop a model for predicting the free energy of a RNA duplex containing a
      single-nucleotide bulge. For bulge loops with adjacent Watson-Crick base pairs,
      neither the identity of the bulge nor the nearest-neighbor base pairs had an
      effect on the influence of the bulge loop on duplex stability. The proposed model
      for prediction of the stability of a duplex containing a bulged nucleotide was
      primarily affected by non-nearest-neighbor interactions. The destabilization of
      the duplex by the bulge was 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. The stability of
      a duplex containing a bulged nucleotide adjacent to a wobble base pair also was
      primarily affected by non-nearest-neighbor interactions. Again, there was a
      direct correlation between the destabilization of the duplex and the stability of
      the less stable duplex stem. However, when one or both of the bulge nearest
      neighbors was a wobble base pair, the free energy increment for insertion of a
      bulge loop is dependent upon the position and orientation of the wobble base pair
      relative the bulged nucleotide. Bulge sequences of the type ((5'UBX)(3'GY)),
      ((5'GBG)(3'UU)) and ((5'UBU)(3'GG)) are less destabilizing by 0.6 kcal/mol, and
      bulge sequences of the type ((5'GBX)(3'UY)) and ((5'XBU)(3'YG)) are more
      destabilizing by 0.4 kcal/mol than bulge loops adjacent to Watson-Crick base
      pairs.

PMID- 18047300
TI  - Heats of formation of triplet ethylene, ethylidene, and acetylene.
AB  - Heats of formation of the lowest triplet state of ethylene and the ground triplet
      state of ethylidene have been predicted by high level electronic structure
      calculations. Total atomization energies obtained from coupled-cluster CCSD(T)
      energies extrapolated to the complete basis set limit using correlation
      consistent basis sets (CBS), plus additional corrections predict the following
      heats of formation in kcal/mol: DeltaH0r(C2H4,3A1) = 80.1 at 0 K and 78.5 at 298
      K, and DeltaH0t(CH3CH,3A' ') = 86.8 at 0 K and 85.1 at 298 K, with an error of
      less than +/-1.0 kcal/mol. The vertical and adiabatic singlet-triplet separation
      energies of ethylene were calculated as DeltaES-T,vert = 104.1 and DeltaES-T,adia
      = 65.8 kcal/mol. These results are in excellent agreement with recent quantum
      Monte Carlo (DMC) values of 103.5 +/- 0.3 and 66.4 +/- 0.3 kcal/mol. Both sets of
      computational values differ from the experimental estimate of 58 +/- 3 kcal/mol
      for the adiabatic splitting. The computed singlet-triplet gap at 0 K for
      acetylene is DeltaES-T,adia(C2H2) = 90.5 kcal/mol, which is in notable
      disagreement with the experimental value of 82.6 kcal/mol. The heat of formation
      of the triplet is DeltaH0tC2H2,3B2) = 145.3 kcal/mol. There is a systematic
      underestimation of the singlet-triplet gaps in recent photodecomposition
      experiments by approximately 7 to 8 kcal/mol. For vinylidene, we predict
      DeltaH0t(H2CC,1A1) = 98.8 kcal/mol at 298 K (exptl. 100.3 +/- 4.0),
      DeltaH0t(H2CC,3B2) = 146.2 at 298 K, and an energy gap DeltaES-T-adia(H2CC) =
      47.7 kcal/mol.

PMID- 18047301
TI  - Near-threshold electron attachment as Regge resonances: cross sections for K, Rb,
      and Cs atoms.
AB  - We investigate the near-threshold formation of negative ions as Regge resonances
      in electron-atom scattering, with specific results obtained for e--K, e--Rb, and
      e--Cs. The complex angular momentum method, implemented within the Mulholland
      formulation of the total elastic cross sections, is employed. We demonstrate that
      for e--K, e--Rb, and e--Cs scattering, the near-threshold electron attachment
      cross sections are characterized by the Wigner threshold behavior, Ramsauer
      Townsend minima, and Regge resonances, all discernible only through Regge partial
      cross section scrutiny. Regge partial, differential, and total elastic cross
      sections are presented and contrasted, as well as the differential cross section
      critical minima.

PMID- 18047302
TI  - High-accuracy extrapolated ab initio thermochemistry of vinyl chloride.
AB  - Applying a modified "high accuracy extrapolated ab initio thermochemistry" (HEAT)
      scheme, the standard heat of formation of vinyl chloride at 0 K is computed to be
      29.79 +/- 1 kJ/mol and at 298.15 K to be 20.9 +/- 2 kJ/mol, thus resolving
      earlier discrepancies among the available experimental values, which span a range
      from 21 up to 38 kJ/mol. The enthalpies of the reactions C2H4 + Cl2 --> CH2CHCl +
      HCl and C2H2 + HCl --> CH2CHCl at 298.15 K are determined to be -123.0 and -113.9
      +/- 2 kJ/mol, respectively.

PMID- 18047303
TI  - Raman investigation of the CO2 complex formation in CO2-acetone mixtures.
AB  - Polarized and depolarized Raman spectra of CO2-acetone mixtures have been
      measured along the isotherm 313 K as a function of CO2 concentration (0.1-0.9
      molar fractions in CO2) by varying the pressure from 0.2 up to 8 MPa. Upon CO2
      addition, a new band appears at about 655 cm(-1) and is assigned to the lower
      frequency nu 2(1) component of the bending mode after degeneracy removal due to
      the formation of a 1:1 electron donor acceptor (EDA) CO2 complex. The equilibrium
      constant associated with the complex formation was estimated and found close to
      those of contact charge transfer complexes. The main modifications of the Fermi
      dyad of CO2 in the mixtures compared with that of pure CO2 at equivalent density
      have been assessed. The band-shape analysis revealed that each dyad component is
      described by two Lorentzian profiles, showing that a tagged CO2 molecule probes
      two kinds of environment in its first shell of neighbors. The first one involves
      nonspecific interactions of CO2 with surrounding acetone whereas the second is
      assigned to the signature of 'transient' CO2 complexes formed with acetone. An
      upper bound life time of the complex has been estimated to be 8 ps. In addition,
      a broad band has been detected between the Fermi dyad peaks at about 1320 cm(-1)
      and its origin interpreted as a further evidence of the CO2-acetone heterodimer
      formation. Finally, the values of the equilibrium concentration of the
      heterodimer versus the total concentration of CO2 deduced from the analysis of
      the nu 2(1) band and from the Fermi dyad have been compared, and the difference
      is interpreted as due to a lack of theoretical approach of Fermi resonance
      transitions associated with species existing in different environments.

PMID- 18047304
TI  - Competition between photochemistry and energy transfer in UV-excited
      diazabenzenes. 4. UV photodissociation of 2,3-, 2,5-, and 2,6-dimethylpyrazine.
AB  - The quantum yield for HCN formation via 248 nm photodissociation of 2,3-, 2,5-,
      and 2,6-dimethylpyrazine (DMP, C6N2H8) was measured using diode laser probing of
      the HCN photoproduct. The total quantum yield is phi = 0.039 +/- 0.07, 0.14 +/-
      0.02, and 0.30 +/- 0.06 for 248 nm excitation of 2,3-, 2,5- and 2,6-DMP,
      respectively. Analysis of the quenching data within the context of a gas kinetic,
      strong collision model allows an estimate of the rate constant for HCN production
      via DMP photodissociation, ks = 4.1 x 10(3), 1.0 x 10(3), and 1.3 x 10(4) s(-1)
      for 2,3-, 2,5- and 2,6-DMP, respectively. Unlike HCN produced from the
      photodissociation of pyrazine and methylpyrazine, the amount of HCN produced via
      a prompt, unquenched dissociation channel was essentially zero, suggesting little
      multiphoton UV absorption. The rate constants for HCN formation together with
      previously measured rate constants for HCN production from photodissociation of
      pyrazine and methylpyrazine have been used to investigate possible reaction
      mechanisms. The position of the methyl group affects the HCN rate constant,
      suggesting that the mechanism for pyrazine dissociation involves an initial step
      that is hindered by the addition of the methyl groups. The proposed initial
      molecular motion of the mechanism, an out-of-plane H atom migration across a N
      atom, is consistent with (1) the position of the methyl groups, (2) the
      dissociation lifetime of the various pyrazine molecules studied, and (3) the
      observed large energy transfer magnitudes from pyrazine near dissociation. These
      so-called "supercollisions" have been linked to low-frequency, out-of-plane
      motion, suggesting that the molecular motions leading to efficient energy
      transfer are the same motions involved in dissociation. In addition, the pyrazine
      (C4N2H4) 248 nm photoproduct (C3H3N) was identified as acrylonitrile using IR
      spectroscopy, an observation that aids in understanding the dissociation
      mechanism.

PMID- 18047305
TI  - Bond dissociation energies and radical stabilization energies: an assessment of
      contemporary theoretical procedures.
AB  - Various contemporary theoretical procedures have been tested for their accuracy
      in predicting the bond dissociation energies (BDEs) and the radical stabilization
      energies (RSEs) for a test set of 22 monosubstituted methyl radicals. The
      procedures considered include the high-level W1, W1', CBS-QB3, ROCBS-QB3, G3(MP2)
      RAD, and G3X(MP2)-RAD methods, unrestricted and restricted versions of the double
      hybrid density functional theory (DFT) procedures B2-PLYP and MPW2-PLYP, and
      unrestricted and restricted versions of the hybrid DFT procedures BMK and MPWB1K,
      as well as the unrestricted DFT procedures UM05 and UM05-2X. The high-level
      composite procedures show very good agreement with experiment and are used to
      evaluate the performance of the comparatively less expensive DFT procedures.
      RMPWB1K and both RBMK and UBMK give very promising results for absolute BDEs,
      while additionally restricted and unrestricted X2-PLYP methods and UM05-2X give
      excellent RSE values. UM05, UB2-PLYP, UMPW2-PLYP, UM05-2X, and UMPWB1K are among
      the less well performing methods for BDEs, while UMPWB1K and UM05 perform less
      well for RSEs. The high-level theoretical results are used to recommend
      alternative experimental BDEs for propyne, acetaldehyde, and acetic acid.

PMID- 18047306
TI  - IR-IR-UV hole-burning: conformation specific IR spectra in the face of UV
      spectral overlap.
AB  - A new technique, IR-IR-UV hole-burning, is reported for obtaining conformation
      specific IR spectra when the electronic spectra are too closely overlapped to
      obtain clean spectra free from interference from other conformations via standard
      ion dip or fluorescence dip methods. The 4'-aminobenzo-15-crown-5 ether-(HDO)
      complex is used as an example, on which the method was applied to prove the
      presence of two conformations having overlapped electronic spectra and to assign
      IR transitions belonging to the same conformation.

PMID- 18047308
TI  - Ultrafast energy transfer in water-AOT reverse micelles.
AB  - A spectroscopic investigation of the vibrational dynamics of water in a
      geometrically confined environment is presented. Reverse micelles of the ternary
      microemulsion H2O/AOT/n-octane (AOT = bis-2-ethylhexyl sulfosuccinate or aerosol
      OT) with diameters ranging from 1 to 10 nm are used as a model system for
      nanoscopic water droplets surrounded by a soft-matter boundary. Femtosecond
      nonlinear infrared spectroscopy in the OH-stretching region of H2O fully confirms
      the core/shell model, in which the entrapped water molecules partition onto two
      molecular subensembles: a bulk-like water core and a hydration layer near the
      ionic surfactant headgroups. These two distinct water species display different
      relaxation kinetics, as they do not exchange vibrational energy. The observed
      spectrotemporal ultrafast response exhibits a local character, indicating that
      the spatial confinement influences approximately one molecular layer located near
      the water-amphiphile boundary. The core of the encapsulated water droplet is
      similar in its spectroscopic properties to the bulk phase of liquid water, i.e.,
      it does not display any true confinement effects such as droplet-size-dependent
      vibrational lifetimes or rotational correlation times. Unlike in bulk water, no
      intermolecular transfer of OH-stretching quanta occurs among the interfacial
      water molecules or from the hydration shell to the bulk-like core, indicating
      that the hydrogen bond network near the H2O/AOT interface is strongly disrupted.

PMID- 18047309
TI  - Physicochemical studies of octadecyl-trimethyl-ammonium bromide: a critical
      assessment of its solution behavior with reference to formation of micelle, and
      microemulsion with n-butanol and n-heptane.
AB  - Octadecyl-trimethyl-ammonium bromide (C18TAB) is a much less studied
      representative in the alkyltrimethylammonium halide surfactant series. A
      comprehensive study of its normal and reverse micelle (microemulsion) formation
      has been herein conducted by the methods of conductometry, tensiometry,
      fluorimetry, and microcalorimetry. The energetics of its air/liquid interfacial
      adsorption and self-association in aqueous solution have been examined. The phase
      behavior of its combinations with water, n-butanol, and n-heptane in the
      formation of microemulsions have been investigated with identification of a
      variety of phases. The energetics of formation of water dispersion in oil (w/o)
      has been evaluated from dilution experiments conducted at different temperatures.
      From the results, structural parameters of the droplets have been determined at
      different [water]/[surfactant] mole ratios (omega) and temperatures. The w/o
      dispersions have evidenced both volume- and temperature-induced conductance
      percolation. The results have been treated in light of the Scaling equations, and
      the associated parameters for the process have been determined. The activation
      energies for the temperature-induced percolation process of the w/o dispersion
      have been evaluated and assessed.

PMID- 18047310
TI  - Ligand-to-metal charge-transfer dynamics in a blue copper protein plastocyanin: a
      molecular dynamics study.
AB  - Equilibrium and nonequilibrium dynamics of a blue copper protein plastocyanin in
      an oxidized state are studied by molecular dynamics (MD) simulation. Potential
      energy functions of the lowest seven electronic states, including ligand-to-metal
      charge-transfer (LMCT) and copper d --> d excited states, were taken from our
      previous work (Ando, K. J. Phys. Chem. B 2004, 108, 3940), which employed ab
      initio molecular orbital and density functional calculations on the active-site
      model. The equilibrium MD simulations in the ground state indicate that ligand
      motions coupled to transition from the ground state to the LMCT state are mostly
      represented by stretching and bending vibrations of the Cu-S(Cys) distance,
      Ndelta(His)-Cu-Ndelta(His) angle, and S(Cys)-Cu-[Ndelta(His)]2 trigonal pyramid
      structure. The nonequilibrium dynamics on the LMCT potential exhibit rapid decays
      in which surface crossings to the d --> d and the first excited states occur in
      70-80 fs. The crossing dynamics mostly correlate with cleavage of the Cu-S(Cys)
      bond and the associated response in the Ndelta(His)-Cu-Ndelta(His) moiety. The
      average dynamics of the vertical energy gap coordinates exhibit an overdamped
      decay with a recurrence oscillation in 500 fs, which shows clear coherence
      surviving after the ensemble averaging. This oscillation stems mostly from the
      recoiling motion of the Ndelta(His)-Cu-Ndelta(His) part. The dynamics of the
      energy gaps after this coherent oscillation are randomized such that the ensemble
      average yields flat profiles along time, although each single trajectory exhibits
      fluctuations with amplitudes large enough to reach surface crossings. These
      indicate that the relaxation from the LMCT state first occurs via ballistic and
      coherent potential crossings in 70-80 and 500 fs, followed by thermally activated
      random transitions.

PMID- 18047311
TI  - Adsorption-induced conformational changes of antifreeze glycoproteins at the
      ice/water interface.
AB  - The conformation of antifreeze glycoprotein (AFGP) molecules adsorbed at the
      ice/water interface was studied by attenuated total reflection (ATR)-FTIR
      spectroscopy. Measurements were carried out for AFGP/D2O solution films formed on
      the surface of an ATR prism as a function of temperature. Using the FTIR spectrum
      from the O-D stretching band of D2O molecules, we monitored the supercooled and
      frozen states of the film and measured the thickness of the quasi-liquid layer
      (QLL) at the ice/prism interfaces. The AFGP structure was determined for the
      liquid, supercooled, and frozen states of the solution film using the amide I
      band spectra. No noticeable differences in conformation were observed in the
      solution conformation from room temperature down to the 15 K supercooling
      studied, whereas the alpha-helical content of AFGP suddenly increased when the
      supercooled solution film froze at -15 degrees C. This change in conformation can
      increase the overall interaction between the AFGP molecules and ice surface and
      allow a stronger adsorption. In contrast, the alpha-helical content of AFGP in
      the frozen film gradually decreased with increasing temperature and finally
      returned to its solution-state level at the melting point of D2O ice. This
      gradual decrease in the alpha-helix content directly correlates with the measured
      increase in QLL thickness. Finally, we conclude that the differences in the alpha
      helix signals between the frozen and supercooled states indicate the
      conformational change of AFGP molecules upon adsorption at the ice/water
      interface, emphasizing the importance of the structure-function relationship,
      even for this highly flexible antifreeze.

PMID- 18047312
TI  - Preparation and characterization of two new water-soluble endohedral
      metallofullerenes as magnetic resonance imaging contrast agents.
AB  - Two new water-soluble Gd-containing endohedral metallofullerenes [ScxGd3
      xN@C80OmOHn (x = 1, 2; m approximately 12; n approximately 26)] were synthesized
      in a simple one-step reaction and characterized by Fourier transform (FT)-IR as
      well as X-ray photoelectron spectroscopy (XPS). Their observed longitudinal
      relaxivities (R1) for water protons are 20.7 and 17.6 mM(-1) s(-1), respectively,
      which are significantly higher than that of the commercial magnetic resonance
      imaging (MRI) contrast agent (Gd-DTPA, 3.2 mM(-1) s(-1)). These results indicate
      these trimetallic nitride endohedral fullerenols are potential next-generation
      high-efficiency MRI contrast agents.

PMID- 18047313
TI  - Structural effects of phosphorus inclusion in bioactive silicate glasses.
AB  - Molecular dynamics simulations of four bioactive silicate glasses containing
      between 0 (P0) and 12 (P12) mol % P2O5 have been carried out in order to
      elucidate the structural role of phosphorus in these materials. In particular, we
      have focused on structural features which can have a direct role in the bioactive
      mechanism of dissolution and bone bonding. The higher affinity of modifier Na and
      Ca cations for coordinating phosphate rather than silicate, together with the
      formation of P-O-Si linkages, lead to increasing repolymerization of the silicate
      network with increasing P2O5 content, which in principle would represent a
      negative effect of P inclusion on the glass bioactivity. However, this effect is
      counterbalanced by the concomitant increase in the amount of free orthophosphate
      groups, whose fast release is deemed to enhance the bioactivity. The strong
      affinity of the orthophosphates for calcium ions leads to a clear tendency toward
      separation of silicate-rich and phosphate-rich phases for the P12 composition.
      Although this could reduce the bioactivity in the case of P12, in general, the
      favorable balance between the effects mentioned above should result in a positive
      effect of partial Si --> P substitution on the glass bioactivity.

PMID- 18047314
TI  - Diffusion-influenced reversible geminate ABCD reaction in the presence of an
      external field.
AB  - We investigate a diffusion-influenced ground-state reversible geminate ABCD
      reaction in the presence of a constant external field in one dimension. In the
      Laplace domain, we first obtain the nonreactive Green function from which the
      reactive Green function is derived. Analytic asymptotic expressions of the
      survival probability are obtained in the time domain for both short and long time
      regions. There exist four regimes for the equilibrium survival probability
      according to the signs of the field intensities a1 and a2 that reactant and
      product states feel, respectively. Analysis of the long-time asymptotic behavior
      of the survival probability shows two regimes depending on the sign of a
      parameter K( identical with a(2)(2)D(2) -a(2)(1)D(1)), where D(1) and D(2) are
      the relative diffusion constants of corresponding states, respectively. Combining
      these two results, we predict a total of eight regimes for the long-time
      asymptotic behavior of the survival probability. We find that the long-time
      asymptotic behavior of the deviation of the effective survival probability shows
      the t(-3/2) power law when m( identical with min {a(2)(1)D(1), a(2)(2)D(2)}) not
      equal 0, whereas it shows t(-1/2) power law when m = 0. When one of the fields is
      turned off, the long-time asymptotic behavior of the survival probability shows a
      kinetic transition as the sign of the remaining field changes.

PMID- 18047315
TI  - Vapor pressure and sublimation rate of molecular crystals: role of internal
      degrees of freedom.
AB  - It is a common practice to approximate the desorption rate of atoms from crystal
      surfaces with an expression of the form nueff exp(-DeltaE/kBT), where DeltaE is
      an activation barrier to desorb and nueff is an effective vibrational frequency
      approximately 10(12) s(-1). For molecular solids, however, such an approximation
      can lead to a many orders of magnitude underestimation of vapor pressure and
      sublimation rates due to neglected contributions from molecular internal degrees
      of freedom. Here, we develop a simple working formula that yields good estimates
      for a general molecular (or atomic) solid and illustrate the approach by
      computing equilibrium vapor pressure of three different molecular solids and an
      atomic solid, as well as the desorption rate of a foreign (inhibitor) molecule
      from the surface of a molecular solid.

PMID- 18047316
TI  - Dynamics of liquid crystalline gelation of DNA.
AB  - DNA liquid crystalline gel (LCG) films have been prepared by immersing DNA
      aqueous borate solutions sandwiched between two circular glass plates into cobalt
      chloride solutions. The time courses of the thickness, the weight fractions of
      DNA and cobalt cations, and the birefringence and turbidity of the film consisted
      of outer DNA LCG and inner DNA amorphous gel or solution have been measured. To
      clarify the mechanism of the process forming LCG, the theory based on the
      nonequilibrium thermodynamics with "moving boundary picture" [Langmuir 2005, 21,
      8155-8160] was modified, and the results were analyzed by the modified theory. It
      was found that the growth process of DNA LCG consists of two dynamics: cobalt
      cation diffusion-limited process at the early stage and the DNA circumstance
      change limited process at the later stage.

PMID- 18047317
TI  - Ultrafast optical pump-probe studies of the cytochrome b(6)f complex in solution
      and crystalline states.
AB  - The cytochrome b6f complex of oxygenic photosynthesis contains a single
      chlorophyll a (Chl a) molecule whose function is presently unknown. The singlet
      excited state of the Chl a molecule is quenched by the surrounding protein
      matrix, and thus the Chl a molecule in the b6f complex may serve as an
      exceptionally sensitive probe of the protein structure. For the first time,
      singlet excited-state dynamics were measured in well-diffracting crystals using
      femtosecond time-resolved optical pump-probe methodology. Lifetimes of the Chl a
      molecule in crystals of the cytochrome b6f complex having different space groups
      were 3-6 times longer than those determined in detergent solutions of the b6f.
      The observed differences in excited state dynamics may arise from small (1-1.5 A)
      changes in the local protein structure caused by crystal packing. The Chl a
      excited state lifetimes measured in the dissolved cytochrome b6f complexes from
      several different species are essentially the same, in spite of differences in
      the local amino acid sequences around the Chl a. This supports an earlier
      hypothesis that the short excited state lifetime of Chl a is critical for the
      function of the b6f complex.

PMID- 18047318
TI  - Chemical stability and characterization of rhodium-diisocyanide coordination
      polymers.
AB  - Poly-[Rh(1,4-phenylene diisocyanide)+4/2(Cl)-] has a two-dimensional template
      structure, where Rh atoms are bonded by the -conjugated 1,4-phenylene
      diisocyanide (pdi) ligands in the x-y plane and through overlapping dz orbitals
      in the z direction. The more conductive metallic bonds in the z direction create
      anisotropy in the electrical conductivity. The anisotropy and unique geometry of
      poly-[Rh(pdi)+4/2(Cl)-] make it a useful test bed for examining the relationship
      between electrical properties and chemical stability in metal-isocyanide
      molecular wire systems. The bulk powder of poly-[Rh(pdi)+4/2(Cl)-] is estimated
      to have a room-temperature bulk conductivity of 3.4 x 10(-11) S x cm(-1), an
      electrical activation energy of 0.9 eV, and a dielectric constant of 7.5. In this
      paper, impedance spectroscopy and X-ray powder diffraction were used to show the
      dependence of the electrical conductivity on the metal-metal bonding of pressed
      bulk powders of poly-[Rh(pdi)+4/2(Cl)-]. Thermo-gravimetric analysis and X-ray
      photoelectron spectroscopy were used to demonstrate air sensitivity in the
      polymer and elucidate the mechanism of oxidative degradation.

PMID- 18047319
TI  - Investigation of the slide of the single layer of the 1,3,5-triamino-2,4,6
      trinitrobenzene crystal: sliding potential and orientation.
AB  - This paper reports for the first time that the sliding potential of a single
      layer of the 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) crystal is within 0-77.9
      kJ per mol unit cell or 0-29.4 MJ/m(3) and that the most possible sliding
      orientation is approximately along one line. As compared to another easy-slide
      material, graphite, TATB has a higher sliding potential and fewer sliding routes
      and furthermore is more difficult to slide. However, TATB can still slide due to
      its highest sliding potential points below the apparent activation energy of the
      decomposition energy of any common explosive. This slide may be the main reason
      as to why TATB can be used as a desensitizer versus mechanical stimuli.

PMID- 18047320
TI  - Transient behavior of the hydrophobic surface/water interface: from nanobubbles
      to organic layer.
AB  - We report the formation and subsequent change of the water-depleted layer at a
      hydrophobic surface/water interface. With water as the solvent, surface plasmon
      resonance measurements indicate time dependent evolution of two separate states.
      The first state is the water-depleted layer, and it is characterized by a layer
      of nanobubbles on the surface and is short-lived in time (order of 10 min). The
      second state is a final equilibrium state, which occurs in approximately 30 h,
      where a layer is formed with organic characteristics. If, instead of water, an
      aqueous solution is exposed to the hydrophobic surface, the evolution from
      nanobubbles to an organic like layer shows dependency on the surface energy of
      the liquid media.

PMID- 18047321
TI  - Thermodynamic modeling of the phase behavior of binary systems of ionic liquids
      and carbon dioxide with the group contribution equation of state.
AB  - The group contribution equation of state (GC-EOS) was applied to predict the
      phase behavior of binary systems of ionic liquids of the homologous families 1
      alkyl-3-methylimidazolium hexafluorophosphate and tetrafluoroborate with CO2.
      Pure group parameters for the new ionic liquid functional groups [-mim][PF6] and
      [-mim][BF4] and interaction parameters between these groups and the paraffin
      (CH3, CH2) and CO2 groups were estimated. The GC-EOS extended with the new
      parameters was applied to predict high-pressure phase equilibria in binary
      mixtures of the ionic liquids [emim][PF6], [bmim][PF6], [hmim][PF6], [bmim][BF4],
      [hmim][BF4], and [omim][BF4] with CO2. The agreement between experimental and
      predicted bubble point data for the ionic liquids was excellent for pressures up
      to 20 MPa, and even for pressures up to about 100 MPa, the agreement was good.
      The results show the capability of the GC-EOS to describe phase equilibria of
      systems consisting of ionic liquids.

PMID- 18047323
TI  - Structural, thermal, and magnetic study of solvation processes in spin-crossover
      [Fe(bpp)(2)][Cr(L)(ox)(2)](2).nH(2)O complexes.
AB  - The influence of lattice water in the magnetic properties of spin-crossover
      [Fe(bpp)2]X2.nH2O salts [bpp = 2,6-bis(pyrazol-3-yl)pyridine] is well-documented.
      In most cases, it stabilizes the low-spin state compared to the anhydrous
      compound. In other cases, it is rather the contrary. Unraveling this mystery
      implies the study of the microscopic changes that accompany the loss of water.
      This might be difficult from an experimental point of view. Our strategy is to
      focus on some salts that undergo a nonreversible dehydration-hydration process
      without loss of crystallinity. By comparison of the structural and magnetic
      properties of original and rehydrated samples, several rules concerning the role
      of water at the microscopic level can be deduced. This paper reports on the
      crystal structure, thermal studies, and magnetic properties of
      [Fe(bpp)2][Cr(bpy)(ox)2]2.2H2O (1), [Fe(bpp)2][Cr(phen)(ox)2]2.0.5H2O.0.5MeOH
      (2), and [Fe(bpp)2][Cr(phen)(ox)2]2.5.5H2O.2.5MeOH (3). Salt 1 contains both high
      spin (HS) and low-spin (LS) Fe2+ cations in a 1:1 ratio. Dehydration yields the
      anhydrous spin-crossover compound with T1/2 downward arrow = 353 K and T1/2
      upward arrow = 369 K. Rehydration affords the dihydrate
      [Fe(bpp)2][Cr(bpy)(ox)2]2.2H2O (1r) with 100% HS Fe2+ sites. Salt 2 also contains
      both HS and LS Fe2+ cations in a 1:1 ratio. Dehydration yields the anhydrous spin
      crossover compound with T1/2 downward arrow = 343 K and T1/2 upward arrow = 348
      K. Rehydration affords [Fe(bpp)2][Cr(phen)(ox)2]2.0.5H2O (2r) with 72% Fe2+ sites
      in the LS configuration. The structural, magnetic, and thermal properties of
      these rehydrated compounds 1r and 2r are also discussed. Finally, 1 has been
      dehydrated and resolvated with MeOH to give [Fe(bpp)2][Cr(bpy)(ox)2]2.MeOH (1s)
      with 33% HS Fe2+ sites. The influence of the guest solvent in the Fe2+ spin state
      can anticipate the future applications of these compounds in solvent sensing.

PMID- 18047324
TI  - Structural diversity and supramolecular aggregation in calcium, strontium, and
      barium salicylates incorporating 1,10-phenanthroline and 4,4'-bipyridine: probing
      the softer side of group 2 metal ions with pyridinic ligands.
AB  - Group 2 metal complexes [Ca(SA)2(phen)]n (1), [Sr2(SA)4(phen)4] (2), and
      [Ba(SA)2(phen)2]n (3) (SA = salicylate) have been obtained by the addition of
      1,10-phenanthroline (phen) to the corresponding metal salicylates, while the
      bipyridine derivatives {[Ca3(SA)6(H2O)4](4bpy)2}n (4),
      {[Sr(SA)2(H2O)3](4bpy)1.5(H2O)}n (5), and {[Ba(SA)2(H2O)3]-(4bpy)1.5(H2O)}n (6)
      have been synthesized starting from the respective metal carbonates, salicylic
      acid (SA-H), and 4,4'-bipyridine (4bpy). The new compounds have been
      characterized by elemental analysis, pH measurements, thermal analysis, and
      spectroscopic measurements (IR, NMR, ultraviolet, and fluorescence). Molecular
      structure determination by single-crystal X-ray diffraction has been carried out
      for all the compounds. The thermal analysis studies indicate the loss of
      coordinated and/or lattice water molecules below 200 degrees C in 4-6 and the
      absence of any coordinated or uncoordinated water molecules in compounds 1-3.
      Compounds 1 and 3-6 exist as one-dimensional polymers while compound 2
      crystallizes as a discrete dimer. Considerable variations have been observed in
      the molecular structures of 1-6 in terms of the geometry around the metal, the
      binding mode of salicylate, and the coordination behavior of the pyridine ligand.
      Calcium ion is hexacoordinated in 1, while in 4 both hexa- and heptacoordinated
      calcium ions are simultaneously present. Strontium exhibits coordination numbers
      of nine and eight in 2 and 5, respectively. The barium ions in 3 and 6 assume
      coordination numbers of eight and seven, respectively. While the OH group of the
      salicylate ligand does not directly bind the metal in 1-3, it coordinates to the
      metal ions in complexes in 4-6 in the un-ionized form. The 4bpy molecules show no
      direct ligation to the metal in 4-6; the phen ligands in 1-3, however, occupy one
      side of the coordination sphere around the metal. The presence of additional O
      H...O, C-H...O, and N-H...O hydrogen bonding and pi-pi stacking in these
      compounds results in the formation of polymeric structures. The results obtained
      for the calcium complexes in this study have been compared with the available
      data in structural calcium chemistry with the aid of a detailed analysis of the
      Cambridge Structural Database.

PMID- 18047325
TI  - Conversion of methanol to 2,2,3-trimethylbutane (triptane) over indium(III)
      iodide.
AB  - InI3 is able to catalyze the conversion of methanol to a mixture of hydrocarbons
      at 200 degrees C with one highly branched alkane, 2,2,3-trimethylbutane
      (triptane), being obtained in high selectivity. The mechanism for InI3-catalyzed
      reactions appears to be basically the same as that proposed for the previously
      studied ZnI2-catalyzed system in which sequential methylation of olefins is
      followed by competing reactions of the resulting carbocation: proton loss to give
      the next olefin vs hydride transfer to give the corresponding alkane. Although
      the reaction conditions and typical triptane yields achievable with ZnI2 and InI3
      are quite similar, the two systems behave rather differently in a number of
      important particulars, including significant differences between the detailed
      product distributions. Most of the differences in behavior can be ascribed to the
      stronger Lewis acidity of InI3, including the ability to activate some alkanes,
      the higher activity for methylation of arenes, and the fact that methanol
      conversion can be observed at somewhat lower temperatures with InI3 than with
      ZnI2.

PMID- 18047326
TI  - Rare examples of transition-metal-main-group metal heterometallic metal-organic
      frameworks from gallium and indium dipyrrinato complexes and silver salts:
      synthesis and framework variability.
AB  - New main-group metal dipyrrinato complexes [M(4-pyrdpm)3], where M = Ga3+ or In3+
      and 4-pyrdpm is the anion of 5-(4-pyridyl)dipyrrin (4-pyrdpmH), have been
      synthesized and incorporated into metal-organic frameworks (MOFs) by reacting the
      dipyrrinato complexes with silver(I) salts. MOFs formed with AgOTf (OTf = O3SCF3)
      and AgSbF6 gave frameworks with three-dimensional (10,3) and two-dimensional
      (6,3) topologies, respectively. In contrast, AgPF6 produced both (10,3) and (6,3)
      network topologies, suggesting that the PF6 anion has little preference for
      templating (10,3) versus (6,3) frameworks within this system. These findings
      update an earlier MOF study that examined the role of these anions in templating
      related heterometallic MOFs which used [Fe(4-pyrdpm)3] and [Co(4-pyrdpm)3]
      metalloligands. All of the dipyrrin compounds reported here have been
      characterized by single-crystal X-ray crystallography, including the first
      crystallographically characterized example of a 1,2,3-unsubstituted free-base
      dipyrrin, 4-pyrdpmH.

PMID- 18047327
TI  - Syntheses and structural characterization of a series of one-dimensional
      fluorotitanophosphates (NH4)(x)K(4-x)[Ti(2)PO(4)F(9)] (x = 0, 0.70, 1.00, 1.25).
AB  - A series of novel fluorotitanophosphates with a general formula (NH4)xK4 -
      x[Ti2PO4F9] (x = 0, 0.70, 1.00, 1.25, named as 1, 2, 3, and 4 respectively) have
      been synthesized under hydrothermal conditions. Their structures were determined
      by X-ray single-crystal diffraction technique, which show that all of the phases
      in this series contain an idental anionic fluorotitanophosphate chain, consisting
      of alternating linkage of PO4 tetrahedra and TiO2F4 octahedra. The
      fluorotitanophosphate chain is unique, which is different from the first
      titanophosphate chain found in [Ti3P6O27].5[NH3CH2-CH2NH3].2H3O. Another
      interesting observation of this series is that, by partial substitution of
      potassium by ammonium, the structure converts to a more-symmetric version, while
      maintaining all of the topological feature.

PMID- 18047328
TI  - Proton-coupled electron transfer in ruthenium(II)-pterin complexes: formation of
      ruthenium-coordinated pterin radicals and their electronic structures.
AB  - Ruthenium(II)-pterin complexes were prepared using tetradentate and tripodal
      tris(2-pyridylmethyl)amine (TPA) and tris(5-methyl-2-pyridylmethyl)amine (5-Me3
      TPA) as auxiliary ligands together with 2-(N,N-dimethyl)-6,7-dimethylpterin
      (Hdmdmp) and 6,7-dimethylpterin (Hdmp) as pterin derivatives for ligands.
      Characterization was made by spectroscopic methods, X-ray crystallography, and
      electrochemical measurements. The pterin ligands coordinated to the ruthenium
      centers as monoanionic bidentate ligands via the 4-oxygen of the pyrimidinone
      moiety and the 5-nitrogen of the pyrazine parts. The striking feature is that the
      coordinated dmp- ligand exhibits a quinonoid structure rather than a deprotonated
      biopterin structure, showing a short C-N bond length for the 2-amino group. Those
      complexes exhibit reversible two-step protonation for both pterin derivatives
      coordinated to the ruthenium centers to give a drastic spectral change in the UV
      vis spectroscopy. Doubly protonated Ru(II)-pterin complexes were stabilized by pi
      back-bonding interaction and exhibited clear and reversible proton-coupled
      electron transfer (PCET) to give ruthenium-coordinated neutral monohydropterin
      radicals as intermediates of PCET processes. Those ESR spectra indicate that the
      unpaired electron delocalizes onto the PCET region (N5-C6-C7-N8) of the pyrazine
      moiety.

PMID- 18047329
TI  - Tetrakis- and tris(1-Methyluracil) complexes of Pt(II): formation and properties
      of a carbon-bonded nucleobase species as well as of heternonuclear derivatives.
AB  - The reaction of K2PtCl4 with an excess of 1-methyluracilate (1-MeU) in water at
      60 degrees C leads to the formation of two major products, K2[Pt(1-MeU
      N3)4].10H2O (1) and trans-K[Pt(1-MeU-N3)2(1-MeU-C5)(H2O)].3H2O (2). Addition of
      CuCl2 to an aqueous solution of 2 yields the mixed-metal complex trans-[PtCl(1
      MeU-N3,O4)2(1-MeU-C5,O4)Cu(H2O)].H2O (4). Single-crystal X-ray analysis was
      carried out for 1 and 4. In both compounds, the heterometals (K+ in 1 and Cu2+ in
      4) are bonded to exocyclic oxygens atoms of the 1-MeU ligands, giving rise to
      intermetallic distances of 3.386(2) and 3.528(2) A in 1 and 2.458(1) A in 4. The
      shortness of the Pt-Cu separation in 4 is consistent with a dative bond between
      PtII and CuII. The aqua ligand in 2 is readily substituted by a series of other
      ligands (e.g., 1-MeC, 9-MeGH, and CN-), as demonstrated by 1H NMR spectroscopy,
      with 3J(195Pt-1H(6)) coupling constants being sensitive indicators. Acid-base
      equilibria of 1 and 2 have been studied in detail and reveal some unexpected
      features: 1 has a relatively high basicity, with protonation starting below pH 5,
      and first and second pKa values being ca. 3.4 and 0.4, respectively. These pKa
      values are markedly higher than those of related neutral 2:1 or cationic 1:1
      complexes and are attributed to both charge effects (-2 charge of 1) and a
      favorable stabilization of oxygen-protonated species by the arrangement of four
      exocyclic oxygen groups of 1-MeU ligands at either sides of the platinum
      coordination planes. Whereas in 2, H+ affinities of the three uracil ligands are
      in the normal range, there is a surprisingly low acidity of N(3)H of the C5
      bonded uracil with a pKa of approximately 12.2, which compares with 9.75 for free
      1-methyluracil. This implies that the C5-bonded PtII does not induce the typical
      acidifying effect of a PtII metal entity when bonded to a ring nitrogen atom of a
      neutral nucleobase. Rather, the effect is qualitatively similar to that of a
      metal ion bonded to N3 of an anionic 1-MeU ligand, which likewise increases its
      overall basicity as compared to neutral 1-MeUH.

PMID- 18047331
TI  - Hollowing Sn-doped TiO2 nanospheres via ostwald ripening.
AB  - The well-known physical phenomenon Ostwald ripening in crystal growth has been
      widely employed in template-free fabrication of hollow inorganic nanostructures
      in recent years. Nevertheless, all reported works so far are limited only to
      stoichiometric phase-pure solids. In this work we describe the first
      investigation of doped (nonstoichiometric) materials using Ostwald ripening as a
      means of creating interior space. In particular, we chose the xSnO2-(1 - x)TiO2
      binary system to establish preparative principles for this approach in synthesis
      of structurally and compositionally complex nanomaterials. In this study, uniform
      Sn-doped TiO2 nanospheres with hollow interiors in 100% morphological yield have
      been prepared with an aqueous inorganic route under hydrothermal conditions.
      Furthermore, our structural and surface analyses indicate that Sn4+ ions can be
      introduced linearly into TiO2, and preferred structural phase(s) can also be
      attained (e.g., either anatase or rutile, or their mixtures). Fluoride anions of
      starting reagents are adsorbed on the surface sites of oxygen. The resultant
      anion overlayer may contribute to stabilization of surface and creation of
      repulsive interaction among the freestanding nanospheres. On the basis of these
      findings, we demonstrate that Ostwald ripening can now be employed as a general
      hollowing approach to architect interior spaces for both simple and complex
      nanostructures.

PMID- 18047330
TI  - Immunomagnetic diffractometry for detection of diagnostic serum markers.
AB  - We describe an integrated approach for detection of diagnostic markers using in
      situ assembled optical diffraction gratings in combination with immunomagnetic
      capture. Folate receptor (FR), a serum protein indicative of various cancers, was
      chosen as a model system to demonstrate the potential of the method. Magnetic
      beads coupled to FR antibody were used to capture FR from serum. The FR-bound
      magnetic beads self-assembled onto microcontact-printed folate-coupled BSA (F
      BSA) patterns to form diffraction gratings which served to detect FR by measuring
      the diffraction intensities caused by laser illumination. The FR-containing
      beads, upon binding to the F-BSA surface, served as intrinsic signal enhancement
      agents, circumventing the need for additional enzymatic signal amplification or
      fluorescent labeling steps. With this approach, a detection sensitivity of 700 fM
      (20 pg/mL) was achieved. The potential use of this approach in clinical
      diagnostics was demonstrated by measuring FR concentration in blood samples
      obtained from cancer patients.

PMID- 18047332
TI  - An electronic rationale for observed initiation rates in ruthenium-mediated
      olefin metathesis: charge donation in phosphine and N-heterocyclic carbene
      ligands.
AB  - Ru K-edge XAS data indicate that second generation ruthenium-based olefin
      metathesis precatalysts (L = N-heterocyclic carbene) possess a more electron
      deficient metal center than in the corresponding first generation species (L =
      tricyclohexylphosphine). This surprising effect is also observed from DFT
      calculations and provides a simple rationale for the slow phosphine dissociation
      kinetics previously noted for second-generation metathesis precatalysts.

PMID- 18047333
TI  - A new paradigm for carbon-carbon bond formation: aerobic, copper-templated cross
      coupling.
AB  - Thiol esters and boronic acids react to produce ketones under aerobic conditions
      in the presence of catalytic quantities of a CuI or CuII salt. The reaction
      occurs at reasonable rates between room temperature and 50 degrees C at neutral
      pH using thiol esters derived from bulky 2 degrees amides of thiosalicylamides
      such as those based on N-tert-butyl-2-mercaptobenzamide. In this mechanistically
      unprecedented reaction system, the carbon-carbon bond formation occurs through
      templating of the thiol ester and the boronic acid at copper; the system is
      rendered catalytic in copper under the aerobic conditions.

PMID- 18047334
TI  - Improved optical enrichment of SWNTs through extraction with chiral nanotweezers
      of 2,6-pyridylene-bridged diporphyrins.
AB  - Chiral single-walled carbon nanotubes (SWNTs) have left- and right-handed helical
      structures (M and P, respectively, according to the IUPAC nomenclature). In this
      report, optically active SWNTs were obtained through preferential extraction of
      (M)- or (P)-SWNTs with 2,6-pyridylene-bridged chiral diporphyrins 1. In the
      circular dichroism (CD) spectra, the SWNTs extracted with 1 exhibit much larger
      intensity than those extracted with 1,3-phenylene-bridged chiral diporphyrins 2,
      indicating an improved chiral discrimination ability of 1. In particular, (6,5)
      SWNTs display the most intensified CD signals among the SWNTs extracted with 1.
      In addition, the SWNT extraction ability of 1 has been shown to be considerably
      enhanced in comparison to 2. These improved discrimination and extraction
      abilities of 1 are attributed to the formation of its more stable SWNT complex.
      Computer-calculated energy minimized structures for 1:(6,5)-SWNT complexes show
      that (R)- and (S)-1 form complexes preferentially with (M)- and (P)-(6,5)-SWNTs,
      respectively. These calculations also predict that the 1:(6,5)-SWNT complex is
      approximately 1.6 kcal mol-1 more stable than the corresponding complex of 2,
      accounting for the improved abilities of 1 in the chiral discrimination and
      extraction.

PMID- 18047335
TI  - Ordering of dipeptide chains on Cu surfaces through 2D cocrystallization.
AB  - We report on the induced ordering of dispersed chiral diphenylalanine (Phe-Phe)
      chains grown on the anisotropic Cu(110) and isotropic Cu(100) surfaces. Scanning
      tunneling microscopy (STM) data reveal that 2D extended hybrid molecular motifs
      can be fabricated by utilizing terephthalic acid (TPA) molecules as linkers.
      These act as a molecular "glue" to bridge the isolated Phe-Phe chains without
      altering the global chirality of the final structures. Our results demonstrate
      the applicability and effectiveness of this 2D analogue of the 3D
      cocrystallization approach.

PMID- 18047336
TI  - Anthryl-doped conjugated polyelectrolytes as aggregation-based sensors for
      nonquenching multicationic analytes.
AB  - The fluorescence-based detection of nonquenching, multicationic small molecules
      has been demonstrated using a blue-emitting, polyanionic poly(p-phenylene
      ethynylene) (PPE) doped with green-emitting exciton traps (anthryl units).
      Multicationic amines (spermine, spermidine, and neomycin) were found to
      effectively induce the formation of tightly associated aggregates between the
      polymer chains in solution. This analyte-induced aggregation, which was
      accompanied by enhanced exciton migration in the PPE, ultimately led to a
      visually noticeable blue-to-green fluorescence color change in the solution. The
      aggregation-based sensor exhibited poor sensitivity toward dicationic and
      monocationic amines, demonstrating that a conjugated polyelectrolyte sensor
      relying on nonspecific, electrostatic interactions may still attain a certain
      level of selectivity.

PMID- 18047337
TI  - Rapid vapor-phase fabrication of organic-inorganic hybrid superlattices with
      monolayer precision.
AB  - We report a new layer-by-layer growth method of self-assembled organic multilayer
      thin films based on gas-phase reactions. In the present molecular layer
      deposition (MLD) process, alkylsiloxane self-assembled multilayers (SAMs) were
      grown under vacuum by repeated sequential adsorptions of C=C-terminated
      alkylsilane and titanium hydroxide. The MLD method is a self- limiting layer-by
      layer growth process, and is perfectly compatible with the atomic layer
      deposition (ALD) method. The SAMs films prepared exhibited good thermal and
      mechanical stability, and various unique electrical properties. The MLD method,
      combined with ALD, was applied to the preparation of organic-inorganic hybrid
      nanolaminate films in the ALD chamber. The organic-inorganic hybrid superlattices
      were then used as active mediums for two-terminal electrical bistable devices.
      The advantages of the MLD method with ALD include accurate control of film
      thickness, large-scale uniformity, highly conformal layering, sharp interfaces,
      and a vast library of possible materials. The MLD method with ALD is an ideal
      fabrication technique for various organic-inorganic hybrid superlattices.

PMID- 18047338
TI  - Dynamics of large elongated RNA by NMR carbon relaxation.
AB  - We present an NMR strategy for characterizing picosecond-to-nanosecond internal
      motions in uniformly 13C/15N-labeled RNAs that combines measurements of R1,
      R1rho, and heteronuclear 13C{1H} NOEs for protonated base (C2, C5, C6, and C8)
      and sugar (C1') carbons with a domain elongation strategy for decoupling internal
      from overall motions and residual dipolar coupling (RDC) measurements for
      determining the average RNA global conformation and orientation of the principal
      axis of the axially symmetric rotational diffusion. TROSY-detected pulse
      sequences are presented for the accurate measurement of nucleobase carbon R1 and
      R1rho rates in large RNAs. The relaxation data is analyzed using a model free
      formalism which takes into account the very high anisotropy of overall rotational
      diffusion (Dratio approximately 4.7), asymmetry of the nucleobase CSAs and
      noncollinearity of C-C, C-H dipolar and CSA interactions under the assumption
      that all interaction tensors for a given carbon experience identical isotropic
      internal motions. The approach is demonstrated and validated on an elongated HIV
      1 TAR RNA (taum approximately 18 ns) both in free form and bound to the ligand
      argininamide (ARG). Results show that, while ARG binding reduces the amplitude of
      collective helix motions and local mobility at the binding pocket, it leads to a
      drastic increase in the local mobility of "spacer" bulge residues linking the two
      helices which undergo virtually unrestricted internal motions (S2 approximately
      0.2) in the ARG bound state. Our results establish the ability to quantitatively
      study the dynamics of RNAs which are significantly larger and more anisotropic
      than customarily studied by NMR carbon relaxation.

PMID- 18047339
TI  - Sterically controlled recognition of macromolecular sequence information by
      molecular tweezers.
AB  - Sequence-specific binding is demonstrated between pyrene-based tweezer molecules
      and soluble, high molar mass copolyimides. The binding involves complementary pi
      pi stacking interactions, polymer chain-folding, and hydrogen bonding and is
      extremely sensitive to the steric environment around the pyromellitimide binding
      site. A detailed picture of the intermolecular interactions involved has been
      obtained through single-crystal X-ray studies of tweezer complexes with model
      diimides. Ring-current magnetic shielding of polyimide protons by the pyrene
      "arms" of the tweezer molecule induces large complexation shifts of the
      corresponding 1H NMR resonances, enabling specific triplet sequences to be
      identified by their complexation shifts. Extended comonomer sequences (triplets
      of triplets in which the monomer residues differ only by the presence or absence
      of a methyl group) can be "read" by a mechanism which involves multiple binding
      of tweezer molecules to adjacent diimide residues within the copolymer chain. The
      adjacent-binding model for sequence recognition has been validated by two
      conceptually different sets of tweezer binding experiments. One approach compares
      sequence-recognition events for copolyimides having either restricted or
      unrestricted triple-triplet sequences, and the other makes use of copolymers
      containing both strongly binding and completely nonbinding diimide residues. In
      all cases the nature and relative proportions of triple-triplet sequences
      predicted by the adjacent-binding model are fully consistent with the observed 1H
      NMR data.

PMID- 18047340
TI  - Subdiffraction imaging through the selective donut-mode depletion of thermally
      stable photoswitchable fluorophores: numerical analysis and application to the
      fluorescent protein Dronpa.
AB  - The fast and reversible on/off switching of the fluorescence emission of the GFP
      like fluorescent protein Dronpa has attracted considerable interest for
      applications in subdiffraction imaging. In this paper we study the use of a donut
      mode beam in combination with two more overlapping laser beams to increase the
      imaging resolution through selective switching to the nonfluorescent
      photoswitched state. We devise and run a series of numerical simulations to
      determine suitable photophysical parameters of prospective, thermally stable
      photoswitchable molecules, in terms of photoswitching quantum yields, fatigue
      resistance, and possible presence of transient nonfluorescent states. Many of our
      findings are applicable to other measurements that make use of donut beams, and
      these guidelines can be used in the synthesis and screening of novel
      photoswitchable compounds. We experimentally demonstrate the possibility of
      obtaining increased resolution by making use of the efficient and thermally
      stable Dronpa photoswitching, using equipment that is commonly available.

PMID- 18047341
TI  - Protein nanopores with covalently attached molecular adapters.
AB  - Molecular adapters are crucial for the stochastic sensing of organic analytes
      with alpha-hemolysin (alphaHL) protein nanopores when direct interactions between
      analytes and the pore cannot readily be arranged by conventional protein
      engineering. In our earlier studies, cyclodextrin adapters were lodged
      noncovalently within the lumen of the alphaHL pore. In the present work, we have
      realized the controlled covalent attachment of a beta-cyclodextrin (betaCD)
      adapter in the two possible molecular orientations inside alphaHL pores prepared
      by genetic engineering. There are two advantages to such a covalent system.
      First, the adapter cannot dissociate, which means there are no gaps during
      stochastic detection, a crucial advance for single-molecule exonuclease DNA
      sequencing where the continuous presence of a molecular adapter will be essential
      for reading individual nucleotides. Second, the ability to orient the adapter
      allows analytes to bind through only one of the two entrances to the betaCD
      cavity. We demonstrate that the covalently attached adapters can be used to alter
      the ion selectivity of the alphaHL pore, examine binding events at elevated
      temperatures, and detect analytes with prolonged dwell times.

PMID- 18047342
TI  - Interaction of urea with amino acids: implications for urea-induced protein
      denaturation.
AB  - The molecular mechanism of urea-induced protein denaturation is not yet fully
      understood. Mainly two opposing mechanisms are controversially discussed,
      according to which either hydrophobic, or polar interactions are the dominant
      driving force. To resolve this question, we have investigated the interactions
      between urea and all 20 amino acids by comprehensive molecular dynamics
      simulations of 22 tripeptides. Calculation of atomic contact frequencies between
      the amino acids and solvent molecules revealed a clear profile of solvation
      preferences by either water or urea. Almost all amino acids showed preference for
      contacts with urea molecules, whereas charged and polar amino acids were found to
      have slight preferences for contact with water molecules. Particularly strong
      preference for contacts to urea were seen for aromatic and apolar side-chains, as
      well as for the protein backbone of all amino acids. Further, protein-urea
      hydrogen bonds were found to be significantly weaker than protein-water or water
      water hydrogen bonds. Our results suggest that hydrophobic interactions are the
      dominant driving force, while hydrogen bonds between urea and the protein
      backbone contribute markedly to the overall energetics by avoiding unfavorable
      unsatisfied hydrogen bond sites on the backbone. In summary, we suggest a
      combined mechanism that unifies the two current and seemingly opposing views.

PMID- 18047343
TI  - PELDOR spectroscopy with DOPA-beta2 and NH2Y-alpha2s: distance measurements
      between residues involved in the radical propagation pathway of E. coli
      ribonucleotide reductase.
AB  - Escherichia coli ribonucleotide reductase (RNR) catalyzes the reduction of
      nucleotides to 2'-deoxynucleotides. The active enzyme is a 1:1 complex of two
      homodimeric subunits, alpha2 and beta2. The alpha2 is the site of nucleotide
      reduction, and beta2 harbors a diferric tyrosyl radical (Y122*) cofactor.
      Turnover requires formation of a cysteinyl radical (C439*) in the active site of
      alpha2 at the expense of the Y122* in beta2. A docking model for the alpha2beta2
      interaction and a pathway for radical transfer from beta2 to alpha2 have been
      proposed. This pathway contains three Ys: Y356 in beta2 and Y731/Y730 in alpha2.
      We have previously incorporated 3-hydroxytyrosine and 3-aminotyrosine into these
      residues and showed that they act as radical traps. In this study, we use these
      alpha2/beta2 variants and PELDOR spectroscopy to measure the distance between the
      Y122* in one alphabeta pair and the newly formed radical in the second alphabeta
      pair. The results yield distances that are similar to those predicted by the
      docking model for radical transfer. Further, they support a long-range radical
      initiation process for C439* generation and provide a structural constraint for
      residue Y356, which is thermally labile in all beta2 structures solved to date.

PMID- 18047344
TI  - Conformational dynamics of bistable RNAs studied by time-resolved NMR
      spectroscopy.
AB  - The structural transition between two alternate conformations of bistable RNAs
      has been characterized by time-resolved NMR spectroscopy. The mechanism,
      kinetics, and thermodynamics underlying the global structural transition of
      bistable RNAs were delineated. Both bistable RNA conformations and a partial
      unstructured RNA of identical sequence could be trapped using photolabile
      protecting groups. This trapping allowed for an investigation of the initial
      folding from an unfolded RNA to one of the preferred conformations of the
      bistable RNA and of the structural transitions involved. Folding of the secondary
      structure elements occurs rapidly, while the global structural transition of the
      bistable RNA occurs on a time scale of minutes and shows marked temperature
      dependence. Comparison of these results with bistable systems previously
      investigated leads to the prediction of activation enthalpies (DeltaH++)
      associated with global structural transitions in RNA.

PMID- 18047345
TI  - The dinuclear Zn(II) complex catalyzed cyclization of a series of 2-hydroxypropyl
      aryl phosphate RNA models: progressive change in mechanism from rate-limiting P-O
      bond cleavage to substrate binding.
AB  - A methoxide-bridged dinuclear Zn(II) complex of 1,3-[N,N'-bis(1,5,9
      triazacyclododecane)]propane (1-Zn(II)2:(-OCH3)) was prepared, and its catalysis
      of the cyclization of a series of 2-hydroxypropyl aryl phosphates (4a-g) was
      investigated in methanol at pH 9.8, T = 25degreesC by stopped-flow
      spectrophotometry. An X-ray diffraction structure of the hydroxide analogue of 1
      Zn(II)2:(-OCH3), namely 1-Zn(II)2:(-OH), reveals that each of the Zn(II) ions is
      coordinated by the three N's of the triazacyclododecane units and a bridging
      hydroxide. The cyclizations of substrates 4a-g reveal a progressive change in the
      observed kinetics from Michaelis-Menten saturation kinetics for the poorer
      substrates (4-OCH3 (4g); 4-H (4f); 3-OCH3 (4e); 4-Cl (4d); 3-NO2, (4c)) to second
      order kinetics (linear in 1-Zn(II)2:(-OCH3)) for the better substrates (4-NO2,3
      CH3 (4b); 4-NO2, (4a)). The data are analyzed in terms of a multistep process
      whereby a first formed complex rearranges to a reactive complex with a doubly
      activated phosphate coordinated to both metal ions. The kinetic behavior of the
      series is analyzed in terms of change in rate-limiting step for the catalyzed
      reaction whereby the rate-limiting step for the poorer substrates (4g-c) is the
      chemical step of cyclization of the substrate, while for the better substrates
      (4b,a) the rate-limiting step is binding. The catalysis of the cyclization of
      these substrates is extremely efficient. The kcat/KM values for the catalyzed
      reactions range from 2.75 x 10(5) to 2.3 x 10(4) M-1 s-1, providing an
      acceleration of 1 x 10(8) to 4 x 10(9) relative to the methoxide reaction
      (k2OCH3, which ranges from 2.6 x 10(-3) to 5.9 x 10(-6) M-1 s-1 for 4a-g). At a
      pH of 9.8 where the catalyst is maximally active, the acceleration for the
      substrates ranges from (1 - 4) x 10(12) relative to the background reaction at
      the same pH. Detailed energetics calculations show that the transition state for
      the catalyzed reaction comprising 1-Zn(II)2, methoxide, and 4 is stabilized by
      about -21 to -23 kcal/mol relative to the transition state for the methoxide
      reaction. The pronounced catalytic activity is attributed to a synergism between
      a positively charged catalyst that has high affinity for the substrate and for
      the transition state for cyclization, and a medium effect involving a reduced
      polarity/dielectric constant that complements a reaction where an oppositely
      charged reactant and catalyst experience charge dispersal in the transition
      state.

PMID- 18047346
TI  - Zipper assembly of photoactive rigid-rod naphthalenediimide pi-stack
      architectures on gold nanoparticles and gold electrodes.
AB  - We introduce zipper assembly as a simple and general concept to create complex
      functional architectures on conducting surfaces. Rigid-rod pi-stack architecture
      composed of p-oligophenyl rods and blue naphthalenediimide (NDI) stacks is
      selected as an example. First, short p-quaterphenyl initiators with four anionic
      NDIs are deposited on gold. Then, long p-octiphenyl propagators with eight
      cationic NDIs are added. The lower half of the propagator pi-stacks with the
      initiator, whereas the upper half of the molecule remains free. These cationic
      sticky-ends zip up with anionic propagators to produce anionic sticky-ends, and
      so on. Zipper assembly on gold nanoparticles is demonstrated by the appearance of
      the absorption of face-to-face NDI pi-stacks and the shift of the surface plasmon
      resonance band with increasing layer thickness. Complete inhibition by zipper
      capping demonstrates that zipper assembly affords complex architectures that are
      more ordered than those obtained by conventional layer-by-layer (LBL) approaches.
      Zipper assembly on gold electrodes produces increasing photocurrents with
      increasing number of zipped layers. The photocurrents obtained by this method are
      much higher than those obtained by conventional LBL controls; zipper termination
      by capping cleanly stops any increase in photocurrent.

PMID- 18047347
TI  - DNA-TiO2 nanoconjugates labeled with magnetic resonance contrast agents.
AB  - Recent efforts have shown that nanoscale materials, specifically, metal-based
      nanoparticles, hold particular promise for the development of multifunctional
      imaging probes. These new materials provide the means to chaperone and
      concentrate both drugs and contrast agents in specific organs, tissues, and
      cells. Therefore, we have prepared a Gd(III)-modified DNA-TiO2 semiconducting
      nanoparticle that is detectable in cells by MR imaging. These labeled particles
      are retained at specific subcellular locations via DNA hybridization to
      intracellular targets, hence creating the first nanoparticle system capable of
      targeting specific DNA sequences while being simultaneously detected via MR
      imaging.

PMID- 18047348
TI  - A two-directional approach to a (-)-dictyostatin C11-C23 segment: development of
      a highly diastereoselective, kinetically-controlled Meerwein-Ponndorf-Verley
      reduction.
AB  - A three-step synthesis of a precursor to the C11-C23 segment of (-)-dictyostatin
      is described. The sequence features a sonication-assisted, enantioselective
      double hetero Diels-Alder (HDA) reaction catalyzed by Jacobsen's Cr(III) Schiff
      base catalyst, followed by a novel, highly diastereoselective Meerwein-Ponndorf
      Verley (MPV) reduction of the hydropyranone subunits under kinetic control to
      yield the bis(axial alcohol) 4. Generalized studies of both the HDA and MPV
      methodologies are also described.

PMID- 18047349
TI  - Kinetically favored platination of adenine in the g-rich human telomeric repeat.
AB  - The interactions of PT-ACRAMTU, a cytotoxic platinum-acridine conjugate, with the
      human telomeric G-quadruplex have been studied using in-line high-performance
      liquid chromatography-mass spectrometry and footprinting assays. The conjugate
      reacts significantly faster with quadruplex DNA (t1/2 = 1.2 h) than with double
      stranded DNA, and A-N7, and not G-N7, is the kinetically preferred target, an
      unprecedented reactivity feature in platinum-DNA interactions. Unlike the
      clinical platinum drug cisplatin, which targets the human telomeric sequence
      nonspecifically, the platinum-intercalator technology has the potential to
      produce telomere-specific anticancer agents via a mechanism that kinetically
      discriminates between G and A in the two DNA secondary structures.

PMID- 18047351
TI  - Diastereoselective self-assembly of double- and triple-stranded helicates from a
      D-isomannide derivative.
AB  - Difunctionalization of D-isomannide yielded a bis(bipyridine) ligand bearing four
      stereogenic centers whose diastereoselective self-assembly to enantiomerically
      pure dinuclear helicates upon coordination to different metal ions was
      investigated by NMR and CD spectroscopic as well as ESI mass spectrometric
      methods.

PMID- 18047352
TI  - Electrically-driven chiroptical switches based on axially dissymmetric 1,1'
      binaphthyl and electrochromic viologens: synthesis and optical properties.
AB  - A novel redox type of chiral molecular switch based on axially dissymmetric 1,1'
      binaphthyl and electrochromic 4,4'-bipyridinium exhibits drastic changes in
      absorption and circular dichroism spectra upon electrochemical redox reaction and
      is fully characterized for the electrically driven chiroptical switching
      properties.

PMID- 18047353
TI  - Subphthalocyanine-dehydro[18]annulenes.
AB  - A subphthalocyanine trimer built around a dehydro[18]annulene core was prepared.
      The synthesis was achieved through direct homocoupling of an ortho-diethynyl
      functionalized subphthalocyanine, obtained by palladium-catalyzed cross-coupling
      of the corresponding diiodo-subphthalocyanine with an ethynyl derivative. The
      lower analogue dehydro[12]annulene did not form in these homocoupling conditions.
      The trimers were fully characterized and their electrochemical properties
      investigated.

PMID- 18047355
TI  - Synthesis of thromboxane B2 via ketalization/ring-closing metathesis.
AB  - Total synthesis of thromboxane B2 using intermolecular ketalization followed by
      ring-closing metathesis is reported. Other key steps include a Sharpless
      asymmetric epoxidation to form an oxirane on the endo face of the bicyclic
      acetal, epoxide opening using lithioacetonitrile, an allylic alcohol 1,3
      transposition, and Mitsunobu lactonization.

PMID- 18047354
TI  - Synthetic and biosynthetic studies on FR900482 and mitomycin C: an efficient and
      stereoselective hydroxymethylation of an advanced benzazocane intermediate.
AB  - We report a simple, efficient, and stereoselective Mukaiyama aldol approach to
      install the key hydroxymethyl moiety into the benzazocane framework of FR900482.
      Synthetic investigations revealed that the reaction is highly dependent upon the
      electronics of the aromatic ring. This approach enabled the economical
      introduction of a [13C] label to study the biosynthesis of these structurally and
      biogenetically related natural products. Epimerization of the initially formed
      beta-hydroxy ketone may enable access to mitomycin C or FR900482 biosynthetic
      congeners.

PMID- 18047356
TI  - Synthesis and study of differentially substituted dibenzotetraazafulvalenes.
AB  - A series of functionalized dibenzotetraazafulvalenes have been synthesized and
      characterized using X-ray crystallography, UV-vis spectroscopy, and cyclic
      voltammetry. The solid-state structures, electronic properties, and redox
      potentials of these compounds varied in accordance with the nature of the pendant
      arene substituent.

PMID- 18047357
TI  - Simple palladium(II) precatalyst for Suzuki-Miyaura couplings: efficient
      reactions of benzylic, aryl, heteroaryl, and vinyl coupling partners.
AB  - trans-PdBr(N-Succ)(PPh3)2 (1) is a universally effective precatalyst for Suzuki
      Miyaura cross-couplings of benzylic halides with aryl- or heteroarylboronic
      acids. Substituted aryl halides and halogenated cyclic enones can be cross
      coupled with aryl- or vinylboronic acids in excellent yields. Catalyst recycling
      is also demonstrated.

PMID- 18047358
TI  - New safety-catch photolabile protecting group.
AB  - Photolabile protecting groups have proven their usefulness on many occasions.
      Their versions as linkers are however less attractive, as robustness and real
      orthogonality become critical issues. Safety-catch systems, where a preliminary
      activation phase is necessary, circumvent the problem of premature cleavage. In
      this work, we introduce a new safety-catch photolabile protecting group, whose
      cleavage requires the simultaneous presence of light and a chemical promoter.

PMID- 18047359
TI  - Efficient synthesis of highly substituted Pyrrolin-4-ones via PIFA-mediated
      cyclization reactions of enaminones.
AB  - A convenient and efficient synthesis of highly substituted pyrrolin-4-ones is
      developed via the PIFA-mediated cyclization reactions of readily available
      enaminones, and a mechanism involving sequential cleavage of N-C bond, formation
      of new N-C bond, intramolecular addition reaction, and benzilic acid type
      rearrangement is proposed.

PMID- 18047360
TI  - Ring enlargement of cyclic acetals and ketals: a way to seven-membered nucleoside
      phostones.
AB  - Novel seven-membered nucleoside phostones were prepared by the reaction of
      chlorodiethyl phosphite with 3',5'-acetals or ketals derived from xylo-dT. A
      mechanism for the ring enlargement was proposed, and support for it was provided
      by ab initio calculations.

PMID- 18047361
TI  - Synthesis of (+)-didemniserinolipid B via ketalization/ring-closing metathesis.
AB  - A modular synthesis of didemniserinolipid B is reported. Central to this
      synthesis was the use of a ketalization/ring-closing metathesis (K/RCM) strategy
      to establish the 6,8-dioxabicyclo[3.2.1]octane core. The C10 axial alcohol was
      established via a selective epoxidation, followed by reductive trans-diaxial
      epoxide opening. The serinol and unsaturated ester side chains were introduced by
      a Williamson etherification and cross metathesis, respectively.

PMID- 18047362
TI  - Scope of a novel three-component synthesis of highly functionalized
      pyridines(dagger).
AB  - A mechanistically unique three-component synthesis provides a variety of
      functionalized pyridine derivatives in fair to excellent yields. The scope of
      this reaction was studied with respect to the alkoxyallene, the nitrile, and the
      carboxylic acid. Due to the 4-hydroxy group, these pyridine derivatives are
      suitable precursors for subsequent palladium-catalyzed reactions. Suzuki
      couplings of the corresponding pyridyl nonaflates lead to a variety of pyridine
      and bipyridine derivatives.

PMID- 18047363
TI  - Direct aminoalkylation of arenes and hetarenes via Ni-catalyzed Negishi cross
      coupling reactions.
AB  - A direct room-temperature Ni-catalyzed cross-coupling of aminoalkylzinc halides,
      readily available from the corresponding aminoalkyl chlorides via Grignard
      reagents, with aryl and hetaryl electrophiles, allows a convenient one-step
      preparation of aminoalkyl (het)arenes, bearing a basic tertiary nitrogen in the
      side chain, including piperidine and tropane derivatives. Such aminoalkylarene
      scaffolds are widely present in various biologically active molecules.

PMID- 18047364
TI  - Benzo-21-crown-7/secondary dialkylammonium salt [2]pseudorotaxane- and
      [2]rotaxane-type threaded structures.
AB  - We demonstrate that secondary dialkylammonium salts can thread through the cavity
      of benzo-21-crown-7 to form [2]pseudorotaxanes with binding constants (527-1062 M
      1 in acetone) higher than the corresponding values (135-261 M-1 in acetone) of
      the analogous complexes with their traditionally used host, dibenzo-24-crown-8.
      Based on this new benzo-21-crown-7/secondary dialkylammonium salt recognition
      motif, a [2]rotaxane was successfully prepared. The formation of these threaded
      structures was confirmed by proton NMR spectroscopy, electrospray ionization mass
      spectrometry, and X-ray single crystal analysis.

PMID- 18047365
TI  - ClickFerrophos: new chiral ferrocenyl phosphine ligands synthesized by click
      chemistry and the use of their metal complexes as catalysts for asymmetric
      hydrogenation and allylic substitution.
AB  - The new ferrocenyl P,P- and P,N-ligands 5 and 6 (collectively, "ClickFerrophos")
      were readily prepared in four steps using Click Chemistry methodology, starting
      from the commercially available aminoferrocene 1. Rhodium and ruthenium complexes
      of ClickFerrophos 5 were effective catalysts for the hydrogenation of alkenes and
      ketones, respectively, producing products with up to 99.7% ee. The analogous
      palladium complex with 6 worked well for asymmetric allylic alkylation.

PMID- 18047366
TI  - An efficient synthesis of chiral beta-hydroxy sulfones via ru-catalyzed
      enantioselective hydrogenation in the presence of iodine.
AB  - Ru-SUNPHOS catalyzed asymmetric hydrogenation of a variety of sulfonyl ketones (R
      = alkyl, aryl) in the presence of iodine gave enantioenriched hydroxyl sulfones
      with good catalytic efficiency. Further investigation revealed that the in situ
      generated anhydrous HI is the operating additive.

PMID- 18047367
TI  - Platinum(II)-catalyzed cross-coupling of polyfluoroaryl imines.
AB  - The introduction of fluorine into an organic molecule imparts unique
      physicochemical properties. Not surprisingly, fluorine is increasingly
      incorporated into new drugs and agrochemicals. However, aryl fluoride building
      blocks are only available through synthesis. The ability to cross-couple
      polyfluoroaromatics selectively could provide a convenient route to
      functionalized fluoroaromatics. We report herein the first examples of Pt
      catalyzed cross-coupling of aryl fluorides. The methylated products can
      potentially serve as precursors to a wide range of functionalized fluorinated
      small molecules.

PMID- 18047368
TI  - Electrocatalytic oxidative cleavage of electron-deficient substituted stilbenes
      in acetonitrile-water employing a new high oxidation potential electrocatalyst.
      An electrochemical equivalent of ozonolysis.
AB  - A series of symmetrical and unsymmetrical stilbenes bearing two or more strong
      electron-withdrawing groups were oxidatively cleaved to the corresponding
      aldehydes in high yield by electrocatalytic anodic oxidation in aqueous
      acetonitrile employing a new high oxidation potential triphenylamine
      electrocatalyst. The oxidations apparently involve the corresponding 1,2-diols,
      which are also converted to aldehydes in high yield under the same conditions.

PMID- 18047369
TI  - Enantioselective synthesis of chiral sulfones by Rh-catalyzed asymmetric addition
      of boronic acids to alpha,beta-unsaturated 2-pyridyl sulfones.
AB  - A general and efficient method for the rhodium-catalyzed enantioselective
      catalytic conjugate addition of organoboronic acids to alpha,beta-unsaturated
      sulfones is described. The success of the process relies on the use of alpha,beta
      unsaturated 2-pyridyl sulfones as key metal-coordinating substrates; typical
      sulfones such as vinyl phenyl sulfones are inert under the reaction conditions.
      Among a variety of chiral ligands, Chiraphos provided the best asymmetric
      induction. This rhodium [Rh(acac)(C2H4)2]/Chiraphos catalyst system has a broad
      scope, being applicable to the addition of both aryl and alkenyl boronic acids to
      cis and trans alpha,beta-unsaturated 2-pyridyl sulfones. In most cases,
      especially in the addition of aryl boronic acids, the reactions take place
      cleanly and with high enantioselectivity, affording chiral beta-substituted 2
      pyridyl sulfones in good yields and enantioselectivities (70-92% ee). The sense
      and magnitude of this enantioselectivity have been studied by DFT theoretical
      calculations of the aryl-rhodium insertion step. These calculations strongly
      support the formation of a five-membered pyridyl-rhodium chelated species as the
      most stable complex after the insertion into the C=C bond. These highly
      enantioenriched chiral sulfones are very appealing building blocks in
      enantioselective synthesis. For instance, the straightforward elimination of the
      2-pyridylsulfonyl group by either Julia-Kociensky olefination or
      alkylation/desulfonylation sequences provides a variety of functionalized chiral
      compounds, such as allylic substituted alkenes or beta-substituted ketones and
      esters.

PMID- 18047370
TI  - Fluorinated alcohol mediated displacement of the C10 acetoxy group of
      benzo[a]pyrene-7,8,9,10-tetrahydrotetraol tetraacetates: a new route to diol
      epoxide-deoxyguanosine adducts.
AB  - We describe a novel trifluoroethanol (TFE) or hexafluoropropan-2-ol (HFP)
      mediated substitution reaction of the bay-region C10 acetoxy group in four
      stereoisomeric 7,8,9,10-tetraacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrenes (tetraol
      tetraacetates, two pairs of cis and trans isomers at the 9,10 positions) by the
      exocyclic N2-amino group of O6-allyl-3',5'-di-O-(tert-butyldimethylsilyl)-2'
      deoxyguanosine (3). The tetraacetates are derived from cis and trans hydrolysis
      of (+/-)-7beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10
      tetrahydrobenzo[a]pyrene (B[a]P DE-1) and of (+/-)-7beta,8alpha-dihydroxy
      9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-2) at C-10
      followed by acetylation. Excellent yields and high regioselectivity were
      observed. Similar cis/trans product ratios were observed for each set of cis and
      trans tetraol tetraacetates derived from DE-1 ( approximately 75/25) and from DE
      2 (approximately 67/33) in HFP. This strongly suggests that the substitution
      proceeds via an SN1 mechanism involving a carbocation intermediate that is common
      to the cis and trans tetraacetates. Since it is likely that the cis and trans
      products from 3 arise from different conformations of the carbocation, its
      lifetime must be sufficiently long to permit conformational equilibration before
      its capture by the purine nucleophile. The corresponding reaction of (+/-)-9alpha
      bromo-7beta,8alpha,10beta-triacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrene with 3 in
      HFP was highly regio- and stereoselective and gave exclusively trans 10beta
      adducts. This newly developed substitution reaction provides an attractive
      alternative synthetic strategy for the preparation of polycyclic hydrocarbon
      adducted oligonucleotide building blocks.

PMID- 18047371
TI  - The decarboxylative Blaise reaction.
AB  - Reaction of aryl nitriles with potassium ethyl malonate in the presence of zinc
      chloride and a catalytic amount of Hunig's base provided beta-amino acrylates in
      moderate to good yield. Compared to the classical Blaise reaction, this reaction
      is safer (endothermic), devoid of lacrimatory reagent, and is possible with 0.5
      1.0 equiv of zinc chloride.

PMID- 18047372
TI  - Asymmetric Mannich reaction of dicarbonyl compounds with alpha-amido sulfones
      catalyzed by cinchona alkaloids and synthesis of chiral dihydropyrimidones.
AB  - The highly enantioselective cinchona alkaloid-catalyzed Mannich reaction of
      dicarbonyl compounds with alpha-amido sulfones as acyl imine precursors is
      described. The reaction requires 10 mol % of the cinchona alkaloid catalyst,
      which serves as a general base to generate acyl imines in situ, and aqueous
      Na2CO3 to maintain the concentration of free alkaloid catalyst. The reaction
      products are obtained in good yields and high enantioselectivities, and in
      diastereoselectivities that range from 1:1 to >95:5. The cinchonine-catalyzed
      reactions provide practical access to highly functionalized building blocks which
      have been employed in the synthesis of chiral dihydropyrimidones, a class of
      compounds rich in diverse biological activity. Dihydropyrimidone modifications
      include a highly diastereoselective hydrogenation of the enamide moiety, using an
      H-Cube flow hydrogenator and a Rh(II)-mediated 1,3-dipolar cycloaddition to
      afford highly functionalized complex heterocycles.

PMID- 18047373
TI  - New insight into the reaction of singlet oxygen with sulfur-containing cyclic
      alkenes: dye-sensitized photooxygenation of 5,6-dihydro-1,4-dithiins.
AB  - The reaction of 3-methyl-5,6-dihydro-1,4-dithiins with singlet oxygen affords
      dicarbonyl compounds and/or ring-contracted ketosulfoxides, the latter regio- and
      stereoselectively, depending on the nature of the substituent at C-2 and on the
      reaction conditions. In competition with normal fragmentation, the intermediate
      dioxetanes, derived from [2 + 2] cycloaddition of singlet oxygen to the double
      bond, undergo an intramolecular oxygen transfer to the sulfur-1 atom, leading to
      labile epoxide intermediates. The latter convert to cis- and trans-ketosulfoxides
      through a non-concerted S-4 migration. This pathway is promoted by the electron
      withdrawing group at C-2 and, for monosubstituted amide, by the solvent basicity.
      S-Oxidation of dithiins is insignificant, except for the monosubstituted amide
      derivative or in the presence of protic species, and occurs selectively at the S
      1 atom.

PMID- 18047375
TI  - Molecular complexity from aromatics: a novel, stereoselective route to
      tricyclo[5.2.2.0(1,5)]undecenones, tricyclo[6.2.2.0(1,6)]dodecenones, and
      [n.3.3]propellanes.
AB  - A general stereoselective route to functionalized and substituted tricyclo
      [5.2.2.0(1,5)]undecenones, tricyclo[6.2.2.0(1,6)]dodecenones, and [3.3.3]- and
      [4.3.3]propellanes from simple aromatic precursors is reported. The methodology
      involves generation and cycloaddition of annulated cyclohexa-2,4-dienones with
      various acrylates followed by manipulation of the resulting tricyclic adducts,
      leading to functionalized tricyclo[5.2.2.0(1,5)]undecenones and
      tricyclo[6.2.2.0(1,6)]dodecenones endowed with a beta,gamma-enone chromophore.
      Photochemical reaction of the tricyclic chromophoric systems followed by
      reductive cleavage provided an efficient entry into propellanes.

PMID- 18047374
TI  - Toward selective reactions with C-H bonds: a rationale for the regio- and
      stereochemistry of dichlorocarbene insertions into cyclic hydrocarbons.
AB  - DFT calculations have been performed to study the course of dichlorocarbene
      insertion reactions into alkanes and to better understand the regio- and
      stereoselectivities observed. At the B3LYP/6-31G(d) level of theory, the
      selectivity of dichlorocarbene insertions into a number of hydrocarbons agrees
      well with the obtained experimental results. The reactivity of a specific C-H
      bond is determined by the capacity of the remaining alkyl fragment to effectively
      delocalize the partial positive charge buildup during the reaction. This activity
      can readily be estimated by calculation of the hydride transfer potential (HTP).
      A comparison with the structure and the stability of the corresponding cation is
      useful to emphasize the origins of the selectivity. Dichlorocarbene is also
      predicted to react efficiently with acidic C-H bonds through a nucleophilic
      electrophilic mechanism. In principle, an attack of a carbene on an appropriately
      substituted three-membered ring may lead to fragmentation of the molecule.

PMID- 18047376
TI  - Dynamic transitions in molecularly thin liquid films under frictional sliding.
AB  - The friction properties of the molecularly thin films of an asymmetric ether, 1,3
      dimethylbutyl hexadecyl ether (DBHE), confined between mica surfaces were
      investigated using the surface forces apparatus. Kinetic friction was measured as
      a function of normal load and sliding velocity, and the static friction
      (stiction) was measured as a function of normal load and surface stopping time.
      Kinetic friction measurements exhibited unstable sliding dynamics: the friction
      force exhibited cyclic bumps and valleys in the sliding velocity range from about
      10(-2) to 1 microm/s, but above and below the velocity range, smooth sliding was
      observed. Stop-start experiments showed a stiction spike when surface stopping
      time exceeded a characteristic nucleation time, indicative of the static friction
      state at very low sliding velocity. These results imply that the friction of the
      confined DBHE film has at least three responsible friction states--static
      friction and two different kinetic friction states--depending on the sliding
      velocity. The unstable sliding (bumps and valleys of the friction force) reflects
      the dynamic transition between two different kinetic states. The different
      friction states and their transitions are discussed on the basis of the recent
      experiments and theories of "inverted" stick-slip friction.

PMID- 18047377
TI  - Coordinated NH3-removal-induced hydrogen adsorption of Cu-complex crystals.
AB  - We synthesized a discrete type of organic-inorganic hybrid crystal
      [Cu(ina)2(NH3)2(H2O)2] (ina = isonicotinate). The monomer units connect to each
      other with hydrogen bonds and pi-pi interactions, forming a three-dimensional
      network. Removal of ammonia and water molecules by vacuum heating treatment
      induced a substantial change from nonporous to porous crystals. The resultant
      porous crystals can predominantly adsorb supercritical hydrogen rather than
      nitrogen vapor at 77 K.

PMID- 18047378
TI  - Monomer adsorption on equilateral triangular lattices with attractive first
      neighbor interactions.
AB  - We have recently studied a model of monomer adsorption on infinitely long
      equilateral triangular lattices with terraces of finite width M and nonperiodic
      boundaries. This study was restricted to the case of repulsive adsorbate
      adsorbate first-neighbor interactions but included attractive, repulsive, and
      negligible second-neighbor interactions. The present work extends this study to
      the case of attractive first-neighbors, and the phases are determined, as before,
      with a confidence exceeding 10 significant figures. Phase diagrams are included
      for terrace widths M < or =11. Most of the occupational characteristics of the
      phases fit exact analytic expressions in M. The infinite-M limit of these
      expressions, combined with other analyses, provide the complete phase diagram for
      the infinite two-dimensional lattice. In addition to the empty and full coverage
      phases, there are three phases exhibiting stripe and cluster features that were
      not observed in the case of repulsive first-neighbors.

PMID- 18047379
TI  - Tailor-made surface properties of particles with a hydrophilic or hydrophobic
      polymer shell mediated by supercritical CO2.
AB  - Controlling the surface characteristics of inorganic materials with an organic
      shell is of great interest for control of the properties of the final material. A
      challenge is thus to be able to deposit a polymer shell with different solvation
      properties onto the surface of inorganic particles and to have a good control of
      the thickness of the organic layer without a prefunctionalization of surfaces. We
      demonstrate, in this paper, a method for coating silica particles (170-550 nm),
      used as model substrates, with either a hydrophilic (polyethylene glycol) or a
      hydrophobic polymer (polybutadiene hydroxy terminated) using a supercritical
      antisolvent process (precipitation from a compressed antisolvent). Several
      operating parameters were studied to control precisely the thickness of the
      deposited layer (from 2 to 30 nm), which was characterized using TEM, FESEM, XPS,
      and UV-visible techniques. This work demonstrates that supercritical antisolvent
      processes are powerful methods and good alternatives to conventional coating
      techniques toward the development of hybrid and/or core-shell nanomaterials.

PMID- 18047380
TI  - A computer simulation study of stick-slip transitions in water films confined
      between model hydrophilic surfaces. 1. Monolayer films.
AB  - The shear behavior of monolayer water films confined in a slit-like pore between
      hydrophilic walls is simulated in the quasistatic regime using the grand
      canonical Monte Carlo technique. Each wall is represented as a hexagonal lattice
      of force sites that interact with water through an orientation-dependent hydrogen
      bonding potential. When the walls are in registry, the water oxygen atoms form
      either a crystal- or fluid-like structure, depending on the period of the wall's
      lattice. In both cases, however, the monolayer structure is orientationally
      disordered. Both the crystal- and fluid-like monolayers prove to be capable of
      experiencing well-defined stick-slip transitions, with the largest yield stress
      occurring in the crystal-like case. Beyond the yield point, the crystal-like
      monolayers "melt", but their structure and molecular motion differ in many
      respects from those characteristic of normal fluids.

PMID- 18047382
TI  - Preparation and liquid crystalline properties of spherical cellulose
      nanocrystals.
AB  - A novel kind of spherical cellulose nanocrystal (SCNC) suspension was prepared by
      hydrolysis of microcrystalline cellulose with a mixture of sulfuric acid and
      hydrochloric acid under ultrasonic treatment. The mechanism of SCNC formation and
      the liquid crystalline properties of their suspensions were investigated. A
      suspension of spherical particles was usually inclined to form crystallization
      colloids rather than liquid crystals at high concentration. However, a SCNC
      suspension with high polydispersity (49%) was observed to form the liquid
      crystalline phase, and the liquid crystalline textures changed with increasing
      concentration. This observation offers an approach to the liquid crystal
      formation of highly polydisperse spherical nanoparticles.

PMID- 18047381
TI  - A tetrafluorophenyl activated ester self-assembled monolayer for the
      immobilization of amine-modified oligonucleotides.
AB  - A tetrafluorophenyl (TFP) ester-terminated self-assembled monolayer (SAM) for the
      fabrication of DNA arrays on gold surfaces is described. Activated ester SAMs are
      desirable for biomolecule array fabrication because they readily react with amine
      containing molecules to form a stable amide linkage. N-Hydroxysuccinimide (NHS)
      ester SAMs are commonly used for this purpose but are subject to a competing
      hydrolysis side reaction, limiting their effectiveness under basic conditions.
      TFP was evaluated here as an alternative activated ester leaving group with a
      potentially greater stability under basic conditions. It is shown that TFP SAMs
      are much more stable to basic pH than their NHS analogs and are also more
      hydrophobic, which is an advantage in the fabrication of high-density spotted
      arrays. DNA arrays prepared on TFP SAMs at pH 10 have a 5-fold greater surface
      density of DNA molecules, reduced fluorescence background, and smaller spot radii
      than those prepared on NHS SAM analogs.

PMID- 18047383
TI  - Exciton dissociation and stark effect in the carbon nanotube photocurrent
      spectrum.
AB  - The field-dependent photocurrent spectrum of individual carbon nanotubes is
      measured using a displacement photocurrent technique. A series of peaks is
      observed in the photocurrent corresponding to both excitonic and free carrier
      transitions. The photocurrent peak corresponding to the ground state exciton
      increases by a factor of 200 beyond a critical electric field, and shows both red
      and blue shifts depending on the field regime. This provides evidence for field
      induced mixing between excitonic and free carrier states.

PMID- 18047385
TI  - When NICE says no!

PMID- 18047386
TI  - NICE cost-effectiveness appraisal of cholinesterase inhibitors: was the right
      question posed? Were the best tools used?
AB  - The National Institute for Health and Clinical Excellence (NICE) recently issued
      updated guidance on the use of cholinesterase inhibitors in the treatment of
      Alzheimer's disease. NICE initially recommended that cholinesterase inhibitors no
      longer be used, but final guidance restricted treatment to patients with disease
      of a moderately severe stage. This decision was based largely on results from a
      heavily criticised economic evaluation that used an adaptation of the Assessment
      of Health Economics in Alzheimer's Disease (AHEAD) model. As the developers of
      the AHEAD model, we examined the appropriateness of NICE's economic analyses and
      presentation of results. We attempted to replicate NICE's results by modifying
      the original AHEAD model. Sensitivity analyses were then run using the modified
      AHEAD model to evaluate the extent of uncertainty in predictions. The AHEAD(NICE)
      analyses resulted in an incremental cost-effectiveness ratio for galantamine of
      82,000 pound per QALY gained (year 2003 values) from the perspective of the UK
      NHS and Personal Social Services. This was later revised to 46,000 pound per
      QALY, compared with < 9000 pound per discounted QALY gained (year 2001 values) in
      the original AHEAD model. Using our modified AHEAD with effectiveness estimates
      matching those of AHEAD(NICE), we show that NICE's choice and presentation of
      sensitivity analyses obscured the instability of their estimates. In the final
      NICE evaluation, the recommendation to delay treatment with cholinesterase
      inhibitors until patients have moderately severe disease was based on critical
      assumptions in the economic analyses that had little evidence to support them.
      The case of NICE's guidance on cholinesterase inhibitors highlights the
      importance of transparent and valid economic evaluations and the dangers of using
      inappropriate modelling technologies, basing analyses on a limited subset of the
      available data, and insufficiently reflecting the uncertainty in estimates that
      are intended to inform decision makers.

PMID- 18047387
TI  - Recombinant factor VIIa (eptacog alfa): a pharmacoeconomic review of its use in
      haemophilia in patients with inhibitors to clotting factors VIII or IX.
AB  - Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor
      VII or eptacog alfa) is indicated as an intravenous haemostatic agent in
      haemophilia patients with inhibitors to clotting factors VIII or IX. In
      noncomparative trials in haemophilia patients with inhibitors, on-demand home
      treatment with recombinant factor VIIa was effective in controlling episodes of
      mild to moderate bleeding and well tolerated, with early treatment being
      associated with a greater rate of success and the need for fewer doses than
      delayed treatment. Prophylactic treatment with recombinant factor VIIa was also
      effective in maintaining haemostasis in patients with this indication undergoing
      surgery. Relative to prior treatment with plasma-derived agents, treatment with
      recombinant factor VIIa was associated with improvements in health-related
      quality of life in a cost-utility study in haemophilia patients with inhibitors
      in Australia. In well designed decision-model cost analyses conducted from a
      healthcare payer perspective in several countries, on-demand treatment with
      recombinant factor VIIa to control mild to moderate bleeding episodes in this
      patient population was predicted to be cost saving or cost neutral relative to on
      demand treatment with intravenous activated prothrombin complex concentrate
      (aPCC). Although the acquisition cost of recombinant factor VIIa was greater than
      that of aPCC in some studies, the greater initial efficacy of recombinant factor
      VIIa than aPCC resulted in lower predicted total medical costs. Results were
      generally robust to plausible changes in key parameters. Orthopaedic surgery with
      recombinant factor VIIa to maintain haemostasis in haemophilia patients with
      inhibitors was generally predicted to be cost saving, relative to not having
      surgery, over the medium to long term in modelled cost analyses from a healthcare
      payer perspective in the UK and US. The initial cost of surgery was high, but the
      difference in costs between patients undergoing or not undergoing surgery was
      predicted to decline over time, as savings were realised from the decrease in the
      number of bleeding episodes requiring treatment in patients who underwent
      surgery. In haemophilia patients with inhibitors, recombinant factor VIIa is
      clinically effective in controlling mild to moderate bleeds, and in maintaining
      haemostasis in patients undergoing orthopaedic surgery. Available
      pharmacoeconomic data from several countries, despite inherent limitations,
      support the use of recombinant factor VIIa as a treatment option that is at least
      cost neutral relative to aPCC in treating mild to moderate bleeds in this patient
      population. In addition, orthopaedic surgery with recombinant factor VIIa to
      maintain haemostasis in haemophilia patients with inhibitors is generally cost
      saving relative to not having surgery over the medium to long term, as the
      acquisition costs of recombinant factor VIIa are offset by cost savings resulting
      from the decrease in the number of joint-related bleeds.

PMID- 18047389
TI  - Economic evidence at the local level : options for making it more useful.
AB  - Like other countries, Australia has had some success in incorporating economic
      evidence into national healthcare decisions. However, it has been recognised that
      this coverage does not extend to the local hospital or health region level. An
      extensive body of research has identified barriers to the use of economic
      evidence at the local level, leading some commentators to suggest that economic
      evaluation should only be targeted at national decision-making bodies. Yet, local
      decision makers in Australia and elsewhere make important choices about the
      uptake and diffusion of healthcare technologies. We propose a number of
      interrelated options to address the barriers that currently prohibit the use of
      economic evaluation by local decision makers in many jurisdictions. These include
      wider dissemination of user friendly models, inclusion of assessments of the cost
      impact of interventions on various budgets, and the establishment of an
      authoritative body that ensures the production of high quality economic models.
      It is argued that these options can have a significant impact on the way economic
      evaluations are conducted, reported, disseminated and used.

PMID- 18047388
TI  - Atorvastatin: a pharmacoeconomic review of its use in the primary and secondary
      prevention of cardiovascular events.
AB  - Atorvastatin is a lipid-lowering agent that has been evaluated in a number of
      primary and secondary intervention studies. In the primary prevention trials
      ASCOT-LLA and CARDS, atorvastatin 10 mg/day significantly reduced cardiovascular
      events compared with placebo. A prospectively conducted economic analysis of the
      3.3-year ASCOT-LLA trial showed that atorvastatin was associated with incremental
      cost-effectiveness ratios (ICERs) of euro11,693 (UK) and euro12,673 (Sweden) per
      event avoided (2002 values). Longer-term modelled analyses using data from CARDS
      showed ICERs of euro8046 (Spain) and 6471pound (UK) per QALY gained (2003/2004
      values), and a US analysis showed atorvastatin was dominant versus no statin when
      modelled over the lifetime of a representative US diabetic primary prevention
      population. In a modelled analysis based on results of the IDEAL trial, which
      showed significant reductions in cardiovascular endpoints with high-dose
      atorvastatin (80 mg/day) compared with conventional-dose simvastatin in patients
      with stable coronary heart disease, ICER values were below the commonly used cost
      effectiveness threshold of euro50,000 per QALY gained in Norway, Sweden and
      Denmark, but were above this threshold in Finland (2005 values). A modelled US
      analysis that also included data from IDEAL and other sources showed an ICER of
      $US33,400 per QALY gained, assuming the incremental difference in acquisition
      cost between high-dose atorvastatin and conventional-dose simvastatin was
      $US1.40/day (2005 value). Most cost-effectiveness analyses with atorvastatin in
      patients with acute coronary syndrome used data from the 16-week MIRACL study,
      which showed a significant reduction in cardiovascular events with high-dose
      atorvastatin compared with placebo. Analyses were conducted in North America and
      Europe and showed that 31-86% of the acquisition cost of high-dose atorvastatin
      was offset by reductions in costs associated with cardiovascular events. Across
      five countries, ICER values ranged from approximate $US850 to $US4100 per event
      avoided (2000/2001 values). Another analysis conducted in the US used longer-term
      data and showed that high-dose atorvastatin versus conventional-dose statin was
      associated with an ICER of $US12,900 per QALY gained, assuming the daily
      difference in acquisition cost was $US1.40 (2005 value). In conclusion,
      atorvastatin has demonstrated beneficial effects on various cardiovascular
      endpoints in large, well designed primary and secondary intervention trials.
      These benefits in moderate- to high-risk patients were achieved at a relatively
      low incremental cost and, across the economic analyses, a substantial proportion
      of atorvastatin acquisition costs was offset by reductions in healthcare resource
      use associated with cardiovascular events. Cost-effectiveness analyses based on
      major clinical trials comparing atorvastatin with placebo, usual medical care,
      simvastatin or pravastatin have generally shown that atorvastatin is associated
      with favourable ICER values, often well below commonly used cost-effectiveness
      thresholds. These modelled analyses have the inherent limitation that projecting
      long-term outcomes beyond the time period of a clinical trial imparts a degree of
      uncertainty to the results. Nevertheless, while some findings were sensitive to
      changes in model assumptions, such as the long-term benefits of statin therapy,
      most sensitivity analyses showed that results of the base-case analyses were
      robust to plausible changes in key parameters. Although a clear pattern is not
      evident from available data, intuitively, the value of atorvastatin would be
      expected to increase with the patient's risk for serious cardiovascular events.

PMID- 18047390
TI  - Oral antiplatelet therapy in secondary prevention of cardiovascular events: an
      assessment from the payer's perspective.
AB  - BACKGROUND: A wide variety of oral antiplatelet trials have been carried out, and
      a large number of cost-effectiveness estimates based on them have been published.
      OBJECTIVE: To assess the cost effectiveness of oral antiplatelet treatments in
      the prevention of cardiovascular events. METHODS: A comprehensive literature
      search was carried out in PubMed and the Cochrane Library and the data reviewed.
      Cost-effectiveness or cost-utility studies of oral antiplatelets published since
      2000 were selected. Cost-effectiveness analyses from the perspective of the UK
      NHS were then carried out using a Markov model with a 6-month cycle length and a
      lifetime horizon. Inputs from the CAPRIE, CHARISMA, (PCI)-CURE, CREDO, COMMIT,
      CLARITY, ESPS 2 and ESPRIT trials were included. All estimates of cost found (per
      event avoided, per QALY gained or per life-year gained) were included. Results
      were analysed in light of the National Institute for Health and Clinical
      Excellence (NICE) guidelines for the use of antiplatelets for the prevention of
      cardiovascular events and all estimates were updated to pound (year 2006 values)
      for easy comparison. RESULTS: Of the initial 141 studies found, 21 were included
      in the initial review. The literature and the Markov model subsequently used
      suggest that aspirin (acetylsalicylic acid) dominates placebo for the secondary
      prevention of cardiovascular events, as it is effective, is also less costly and
      is as well tolerated as placebo. Additionally, in periods or patients with
      elevated risk, more intensive treatment with clopidogrel (alone or together with
      aspirin) is cost effective compared with aspirin alone for the secondary
      prevention of ischaemic events. For secondary stroke prevention, combination
      therapy with aspirin and dipyridamole has a favourable incremental cost
      effectiveness ratio (ICER) when compared with aspirin alone and, based on an
      indirect comparison, also when compared with clopidogrel. CONCLUSIONS: The cost
      effectiveness estimates presented in this article support the NICE guidelines for
      the use of antiplatelets for the prevention of cardiovascular events. Based on
      these pharmacoeconomic data alone, aspirin should be prescribed for primary or
      secondary prevention among patients at high risk of cardiovascular events,
      dipyridamole for the secondary prevention of stroke (for a maximum of 5 years),
      and clopidogrel for the treatment of symptomatic cardiovascular disease or acute
      coronary syndrome (for a maximum of 2 years). The cost effectiveness of
      antiplatelets hinges on the patient's initial risk, the risk reduction associated
      with treatment, and the price of the treatment. Evidence suggests that the cost
      effectiveness of antiplatelets can be optimized by individualising the treatment
      decision based on patient risk and expected risk reduction.

PMID- 18047392
TI  - The impact of a rural emergency department rotation on applicant ranking of a US
      emergency medicine residency program.
AB  - INTRODUCTION: Few US emergency medicine (EM) residency programs have been located
      in rural states due to program requirements for emergency department (ED) patient
      volume. Recent revision to the program requirements now permits 'educationally
      justifiable exceptions' to the patient population requirement, 'such as clinical
      sites in a rural setting', and some EM residency programs now plan to offer rural
      ED clinical experiences as a required curricular component. The impact of a
      required rural EM rotation on the ranking decisions of applicants is important to
      residency programs seeking to attract the most desirable applicants. OBJECTIVE:
      To assess the impact of a required rural ED rotation on applicant ranking of an
      EM residency program in the US National Resident Matching Program (NMRP).
      METHODS: All applicants to the study's EM residency program completing the
      interview portion of the application process received a mailed and emailed survey
      following the release of the 2004 NMRP results. The survey included questions
      addressing the rural/non-rural classification of the location of the applicants'
      childhood home, medical school, and anticipated future practice. RESULTS: Of 46
      eligible subjects, 32 (69.6%) completed the survey. Of subjects with a rural
      childhood, 73.3% reported a positive impact on rank order (95% CI 50.9-95.7%) and
      26.7% reported no impact (CI 4.3-49.1%); 81.3% of subjects with non-rural
      backgrounds reported no impact (CI 62.2-100%), 12.5% higher rank (CI 0-28.7%),
      and 6.3% lower (CI 0-18.2%). If planning a future practice in a rural community,
      83.3% reported positive impact (CI 62.2-100%) and 16.7% no impact (CI 0-37.8%);
      78.9% of subjects anticipating future practice in non-rural communities reported
      no impact (CI 60.6-97.3%), 15.8% higher rank (CI 0-32.2%), and 5.3% lower (CI 0
      15.4). Of the subjects attending medical school in rural states, 52.2% reported a
      positive impact (CI 31.8-72.6%) and 47.8% no impact (CI 27.4-68.2%), while 75% of
      graduates of medical schools in non-rural states reported no impact (CI 32.6
      100%) and 25% (CI 0-67.4%) a negative impact. CONCLUSION: The presence of a rural
      ED rotation did not adversely impact EM residency applicants' ranking of the
      program.

PMID- 18047393
TI  - Molecular and proteomic characterization of human mesenchymal stem cells derived
      from amniotic fluid: comparison to bone marrow mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSCs) constitute a population of multipotent
      adherent cells able to give rise to multiple mesenchymal lineages such as
      osteoblasts, adipocytes, or chondrocytes. So far, the most common source of MSCs
      has been the bone marrow (BM); however BM-MSC harvesting and processing exhibits
      major drawbacks and limitations. Thus, identification and characterization of
      alternative sources of MSCs are of great importance. In the present study, we
      isolated and expanded fetal MSCs from second-trimester amniotic fluid (AF). We
      documented that these cells are of embryonic origin, can differentiate under
      appropriate conditions into cell types derived from all three germ layers, and
      express the pluripotency marker Oct-4, the human Nanog protein, and the stage
      specific embryonic antigen-4 (SSEA-4). Furthermore, we systematically tested the
      immunophenotype of cultured MSCs by flow cytometry analysis using a wide variety
      of markers. Direct comparison of this phenotype to the one derived from cultured
      BM-MSCs demonstrated that cultured MSCs from both sources exhibit similar
      expression patterns. Using the two-dimensional gel electrophoresis and matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) approach, we have generated for the first time the protein map of cultured AF
      MSCs by identifying 261 proteins, and we compared it directly to that of cultured
      BM-MSCs. The functional pattern of the identified proteins from both sources was
      similar. However, cultured AF-MSCs displayed a number of unique proteins related
      to proliferation and primitive phenotype, which may confer to the distinct
      features of the two types. Considering the easy access to this new cell source
      and the yield of expanded MSCs for stem cell research, AF may provide an
      excellent source of MSCs both for basic research and for potential therapeutic
      applications.

PMID- 18047394
TI  - Habitat factors influencing distributions of Anaplasma phagocytophilum and
      Ehrlichia chaffeensis in the Mississippi Alluvial Valley.
AB  - Human monocytotropic ehrlichiosis (HME), caused by the bacterium Ehrlichia
      chaffeensis, and human granulocytic anaplasmosis (HGA), caused by the bacterium
      Anaplasma phagocytophilum, are two emerging tick-borne zoonoses of concern.
      Factors influencing geographic distributions of these pathogens are not fully
      understood, especially at varying spatial extents (regional versus landscape) and
      resolutions (counties versus smaller land units). We used logistic regression to
      compare influences of physical environment, land cover composition, and landscape
      heterogeneity on distributions of A. phagocytophilum and E. chaffeensis at
      multiple spatial extents. Pathogen presence or absence was determined from white
      tailed deer (Odocoileus virginianus) serum samples collected from 1981 to 2005.
      Ecological predictor variables were derived from spatial datasets that
      represented deer density, elevation, land cover, normalized difference vegetation
      index (NDVI), hydrology, and soil moisture. We used three strategies (a priori,
      exploratory, and spatial extent) to develop models. Best fitting models were
      applied within a geographic information system to create predictive probability
      surfaces for each bacterium. Ecological predictor variables generally resulted in
      better fitting models for E. chaffeensis than A. phagocytophilum (90.5% and 68%
      sensitivity, respectively), possibly as a result of differences in the natural
      histories of tick vectors. Although alternative model development strategies
      produced different models, in all cases bacteria presence or absence was affected
      by a combination of soil moisture or flooding variables (thought to affect
      primarily tick vectors) and forest cover or NDVI variables (thought to affect
      primarily mammalian hosts). This research demonstrates the potential for modeling
      the distributions of microscopic tick-borne pathogens using coarse regional
      datasets and emphasizes the importance of forest cover and flooding as
      environmental constraints, as well as the importance of considering ecological
      variables at multiple spatial extents.

PMID- 18047395
TI  - Climate change effects on plague and tularemia in the United States.
AB  - Plague and tularemia are serious zoonotic diseases endemic to North America. We
      evaluated spatial patterns in their transmission in view of changing climates.
      First, we tested whether observed shifts since the 1960s are consistent with
      expected patterns of shift given known climate changes over that period. Then, we
      used general circulation model results summarizing global patterns of changing
      climates into the future to forecast likely shifts in patterns of transmission
      over the next 50 years. The results indicate that these diseases are indeed
      shifting in accord with patterns of climatic shift, but that overall geographic
      shifts will likely be subtle, with some northward movement of southern limits and
      possibly northward movement of northern limits as well.

PMID- 18047396
TI  - Submitter and technician observations, and animal rabies detection in
      Massachusetts, 1992-2006.
AB  - A relationship was detected between the submitter and technician observations and
      animal rabies detection in Massachusetts during 1992-2006 by logistic regression
      and Fisher exact testing. The results suggested that aggression (OR = 3.94, p <
      0.0001), disorientation (OR = 1.17, p = 0.0006), paralysis (OR = 1.22, p =
      0.041), unexplained wound (OR = 1.472, p < 0.0001), and found dead (OR = 1.16, p
      = 0.0089) were independently associated with positive rabies testing results at
      alpha 0.05 level adjusted by categorized animal species and type of animal.
      Fisher exact test confirmed the relationship between embedded porcupine quills
      and skunk spray of rabies-tested animals with positive rabies testing results.

PMID- 18047397
TI  - Modeling the spatial distribution of crimean-congo hemorrhagic fever outbreaks in
      Turkey.
AB  - The more than 1100 human cases of Crimean-Congo Hemorrhagic Fever (CCHF) reported
      in a continuing series of outbreaks that started in 2003 in Turkey constitute the
      largest epidemic of the disease since CCHF was first recognized in 1944. The
      spatial distribution of CCHF case reporting rates in Turkey was studied to look
      for clusters of disease. We applied the spatial scan analysis to test the
      hypothesis of whether there were areas with a higher than expected number of CCHF
      cases. The analysis was conducted through windows of 10, 20, 40 and 80 km in
      diameter[SR1] to determine whether clustering of cases was dependent on the size
      of the scanning window. At the largest window size, consistent patterns of
      significantly higher than expected numbers of CCHF cases were found in a total of
      40 administrative districts. A predictive model to map the habitat suitability
      for the vector tick was developed from satellite-based climate data and high
      resolution features of the vegetation from Landsat images covering the whole
      country. It was found that areas of higher risk (higher CCHF reporting) were
      correlated (p<0.05) with zones of high climate suitability for the tick together
      with a high rate of fragmentation of agricultural land interspersed between
      forest and shrub-type vegetation.

PMID- 18047398
TI  - Differential exposure to Anaplasma phagocytophilum in rodent species in northern
      California.
AB  - Anaplasma phagocytophilum is a zoonotic tick-borne rickettsial pathogen that
      causes granulocytic anaplasmosis (GA) in humans, horses, and dogs. In California,
      dusky-footed woodrats (Neotoma fuscipes) are a putative reservoir host, and
      Ixodes pacificus is a vector for transmission from rodents to humans, dogs, and
      horses. Cases are clustered in coastal and Sierra Nevada foothill regions, but
      not necessarily in proximity to infected woodrats. This study was designed to
      compare exposures and active infections of A. phagocytophilum in multiple rodents
      at a fine spatial scale in a hyperenzootic area and to evaluate the spatial
      clustering of infections. Of 331 rodents, the seroprevalence was 14.5%, with 60%
      in tree squirrels (Sciurus griseus and Tamiasciurus douglasii), 29% in woodrats,
      14% in flying squirrels (Glaucomys sabrinus), and 5% in chipmunks (Tamias senex).
      No seropositive ground squirrels (Spermophilus beecheyi) were detected. The
      seroprevalence was significantly higher west of the Trinity River (23.1%) than
      east (11.8%) of the river. One Douglas squirrel and one western gray squirrel
      were polymerase chain reaction (PCR) positive. There was more spatial clustering
      among seropositive animals compared with all animals tested across the spatial
      scales evaluated, and this clustering was significantly greater than expected by
      chance alone. A significant cluster of 24 seropositive animals was found west of
      the Trinity River, with a population of 56 animals considered within the 50%
      population-at-risk, and a radius of 362.8 meters. The diversity of cricetine and
      sciurid rodents infected suggests that squirrels and chipmunks may be
      underappreciated contributors to A. phagocytophilum ecology in the western United
      States. The spatial clustering of exposed animals suggests interesting underlying
      spatially heterogeneous environmental variables that could facilitate the
      persistence of A. phagocytophilum in nature.

PMID- 18047399
TI  - The effect of the copper chelator tetraethylenepentamine on reactive oxygen
      species generation by human hematopoietic progenitor cells.
AB  - Clinical observations suggest that copper (Cu) plays a role in regulating
      hematopoietic progenitor cell (HPC) development. Cu is known to generate
      oxidative stress in cells which in turn affects proliferation, differentiation
      and apoptosis. To study this role of Cu, we used double staining flow cytometry
      to measure reactive oxygen species (ROS) generation by neonatal cord blood
      derived CD34(+)CD38(-) cells. ROS was increased by Cu and was decreased by the Cu
      chelator tetraethylenepentamine (TEPA). Previously, we showed that TEPA reduces
      the free Cu content of HPCs and stimulates their ex vivo expansion. The present
      results suggest that TEPA affects expansion of HPCs by lowering their oxidative
      stress.

PMID- 18047400
TI  - Image reconstruction in positron emission tomography (PET): the 90th anniversary
      of Radon's solution.
AB  - This year is the 90th anniversary of Radon's solution of how the values of a
      function can be reconstructed from measured line integrals. In medical
      tomography, Radon's method allows the formation of cross-sectional images of a
      human's body from measurements outside the patient. This paper reviews the use of
      Radon's method in positron emission tomography (PET) and presents some future
      trends in PET.

PMID- 18047401
TI  - [Registration of fundus images for generating wide field composite images of the
      retina ].
AB  - The composition of retinal images presents high demands to the applied methods.
      Substantially different lighting conditions between the images, glarings and fade
      outs within one image, large textureless regions and non-linear distortions are
      the main challenges. We present a fully automatic algorithm for the registration
      of images of the human retina and their overlay to wide field montage images
      combining area-based and point-based approaches. The algorithm combines an area
      based as well as a point-based approach for determining similarities between
      images. Various measures of similarity were investigated, where the normalized
      correlation coefficient was superior compared to the usual definitions of
      transinformation. The transformation of the images was based on a quadratic model
      that can be derived from the spherical surface of the retina. This model was
      compared to four other parameterized transformations and performed best both
      visually and quantitatively in terms of measured misregistration. Problems may
      occur if the images are extremely defocused or contain very little relevant
      structural information.

PMID- 18047402
TI  - [ElePhant: an anatomic-electronic simulation system for the evaluation of
      computer assisted interventions and surgical education].
AB  - BACKGROUND: Suitable simulation systems providing realistic conditions are
      required for preclinical evaluation of computer assisted interventions and
      surgical training. Techniques are necessary for an objective detection of
      injuries to the structures at risk. The aim of this study was the technical
      realization of a simulation system for the ENT intervention, mastoidectomy.
      MATERIALS AND METHODS: The basis of the simulation system was a CT scan of a
      cadaver skull. Using 3D printing, an anatomical phantom with realistic bone-like
      properties was created. Electronic detection systems were integrated into the
      structures at risk. A study with 16 ENT surgeons was conducted to prove the
      system's suitability for surgical training. RESULTS: The creation of simulation
      systems for the objective evaluation of surgical intervention qualities is
      feasible. A modular structure enables economic and simple replacement of the
      simulation area. The modules are cost effective and reproducible with high
      accuracy. The present study shows that the simulation system can be applied in
      surgical education and evaluation as an alternative to cadavers. CONCLUSION:
      Objective evaluation of injured structures at risk can be realized in real time.
      The simulation system permits preclinical evaluation studies of computer assisted
      instruments and surgical education. Reproducibility of the results makes multi
      center studies possible.

PMID- 18047403
TI  - An easily reproducible and biomechanically standardized model to investigate bone
      healing in rats, using external fixation.
AB  - Abstract We have established a new small animal model to investigate the process
      of bone regeneration. A total of 42 male Sprague-Dawley rats received an
      osteotomy of the left femur, stabilized with a custom-made external fixator. The
      fixation method was chosen to create an easily reproducible, biomechanically well
      defined model with minimized interference of the implant with the healing zone.
      At 14 or 56 days post-operation, the animals were sacrificed and examined
      biomechanically, histologically and radiologically. Radiologically, the femurs of
      all animals were anatomically positioned directly post-operation and remained in
      that position throughout the examination period. At 14 days post-operation, a
      typical periosteal callus formation could be observed both histologically and
      radiologically. At 56 days post-operation, the osteotomy was almost completely
      bridged by periosteal callus and the biomechanical competence of the bones was
      fully restored. Relative to the intact contralateral femur, the torsional
      stiffness median was 130.3% (interquartile range 118.9-157.7%) and the maximum
      torsional failure moment median was 135.6% (interquartile range 69.5-208.7%). As
      this model provides standardized conditions, it is suitable for a wide range of
      investigations and is particularly valuable for investigations of locally applied
      therapies, such as osteoconductive materials or osteoinductive factors.

PMID- 18047404
TI  - [ Improvement of femoral bone-cement adhesion in cemented revision hip
      arthroplasty by application of an amphiphilic bonder in a dynamic femur expulsion
      testing in vitro ].
AB  - Cemented femoral stems have shown decreased longevity compared to cementless
      implants in hip revision arthroplasty. The aim of this study was to evaluate the
      effect of an amphiphilic bonder on bone cement stability in a biomechanical femur
      expulsion test. A simplified hip simulator test setup with idealised femur stem
      specimens was carried out. The stems were implanted into bovine femurs (group 1:
      no bonder, n=10; group 2: bonder including glutaraldehyde, n=10; group 3: bonder
      without glutaraldehyde, n=10). A dynamic loading (maximum load: 800 N; minimum
      load: 100 N; frequency: 3 Hz; 105 cycles) was performed. Subsequently, the stem
      specimens were expulsed axially out of their implant beds and maximum load at
      failure was recorded. The static controls showed a mean maximum load to failure
      of 4123 N in group 1, 8357.5 N in group 2 and 5830.8 N in group 3. After dynamic
      loading, the specimens of group 2 reached the highest load to failure (8191.5 N),
      followed by group 3 (5649.5 N) and group 1 (3462 N), respectively. In group 2, we
      observed nine periprosthetic fractures at a load of 8400 N without signs of
      interface loosening. Application of an amphiphilic bonder led to a significant
      improvement of bonding stability, especially when glutaraldehyde was added to the
      bonder. This technique might offer an increased longevity of cemented femur
      revision stems in total hip replacement.

PMID- 18047408
TI  - Inhomogeneities in heteroassociative memories with linear learning rules.
AB  - We investigate how various inhomogeneities present in synapses and neurons affect
      the performance of feedforward associative memories with linear learning, a high
      level network model of hippocampal circuitry and plasticity. The inhomogeneities
      incorporated into the model are differential input attenuation, stochastic
      synaptic transmission, and memories learned with varying intensity. For a class
      of local learning rules, we determine the memory capacity of the model by
      extending previous analysis. We find that the signal-to-noise ratio (SNR), a
      measure of fidelity of recall, depends on the coefficients of variation (CVs) of
      the attenuation factors, the transmission variables, and the intensity of the
      memories, as well as the parameters of the learning rule, pattern sparsity and
      the number of memories stored. To predict the effects of attenuation due to
      extended dendritic trees, we use distributions of attenuations appropriate to
      unbranched and branched dendritic trees. Biological parameters for stochastic
      transmission are used to determine the CV of the transmission factors. The
      reduction in SNR due to differential attenuation is surprisingly low compared to
      the reduction due to stochastic transmission. Training a network by storing
      memories at different intensities is equivalent to using a learning rule
      incorporating weight decay. In this type of network, new memories can be stored
      continuously at the expense of older ones being forgotten (a palimpsest). We show
      that there is an optimal rate of weight decay that maximizes the capacity of the
      network, which is a factor of e lower than its nonpalimpsest equivalent.

PMID- 18047409
TI  - Gamma oscillations and stimulus selection.
AB  - More coherent excitatory stimuli are known to have a competitive advantage over
      less coherent ones. We show here that this advantage is amplified greatly when
      the target includes inhibitory interneurons acting via GABA(A)-receptor-mediated
      synapses and the coherent input oscillates at gamma frequency. We hypothesize
      that therein lies, at least in part, the functional significance of the
      experimentally observed link between attentional biasing of stimulus competition
      and gamma frequency rhythmicity.

PMID- 18047410
TI  - Populations of tightly coupled neurons: the RGC/LGN system.
AB  - A mathematical model, of general character for the dynamic description of coupled
      neural oscillators is presented. The population approach that is employed applies
      equally to coupled cells as to populations of such coupled cells. The formulation
      includes stochasticity and preserves details of precisely firing neurons. Based
      on the generally accepted view of cortical wiring, this formulation is applied to
      the retinal ganglion cell (RGC)/lateral geniculate nucleus (LGN) relay cell
      system, of the early mammalian visual system. The smallness of quantal voltage
      jumps at the retinal level permits a Fokker-Planck approximation for the RGC
      contribution; however, the LGN description requires the use of finite jumps,
      which for fast synaptic dynamics appears as finite jumps in the membrane
      potential. Analyses of equilibrium spiking behavior for both the deterministic
      and stochastic cases are presented. Green's function methods form the basis for
      the asymptotic and exact results that are presented. This determines the spiking
      ratio (i.e., the number of RGC arrivals per LGN spike), which is the reciprocal
      of the transfer ratio, under wide circumstances. Criteria for spiking regimes, in
      terms of the relatively few parameters of the model, are presented. Under
      reasonable hypotheses, it is shown that the transfer ratio is <or=1/2, in the
      absence of input from other areas. Thus, the model suggests that the LGN/RGC
      system may be a relatively unsophisticated spike editor. In the absence of other
      input, the system is designed to fire an LGN spike only when two or more RGC
      spikes appear in a relatively short time. Transfer ratios that briefly exceed 1/2
      (but are less than 1) have been recorded in the laboratory. Inclusion of brain
      stem input has been shown to provide a signal that elevates the transfer ratio
      (Ozaki & Kaplan, 2006). A model that includes this contribution is also
      presented.

PMID- 18047411
TI  - Brain reading using full brain support vector machines for object recognition:
      there is no "face" identification area.
AB  - Over the past decade, object recognition work has confounded voxel response
      detection with potential voxel class identification. Consequently, the claim that
      there are areas of the brain that are necessary and sufficient for object
      identification cannot be resolved with existing associative methods (e.g., the
      general linear model) that are dominant in brain imaging methods. In order to
      explore this controversy we trained full brain (40,000 voxels) single TR
      (repetition time) classifiers on data from 10 subjects in two different
      recognition tasks on the most controversial classes of stimuli (house and face)
      and show 97.4% median out-of-sample (unseen TRs) generalization. This performance
      allowed us to reliably and uniquely assay the classifier's voxel diagnosticity in
      all individual subjects' brains. In this two-class case, there may be specific
      areas diagnostic for house stimuli (e.g., LO) or for face stimuli (e.g., STS);
      however, in contrast to the detection results common in this literature, neither
      the fusiform face area nor parahippocampal place area is shown to be uniquely
      diagnostic for faces or places, respectively.

PMID- 18047412
TI  - Efficient tracking of the dominant eigenspace of a normalized kernel matrix.
AB  - Various machine learning problems rely on kernel-based methods. The power of
      these methods resides in the ability to solve highly nonlinear problems by
      reformulating them in a linear context. The dominant eigenspace of a (normalized)
      kernel matrix is often required. Unfortunately, the computational requirements of
      the existing kernel methods are such that the applicability is restricted to
      relatively small data sets. This letter therefore focuses on a kernel-based
      method for large data sets. More specifically, a numerically stable tracking
      algorithm for the dominant eigenspace of a normalized kernel matrix is proposed,
      which proceeds by an updating (the addition of a new data point) followed by a
      downdating (the exclusion of an old data point) of the kernel matrix. Testing the
      algorithm on some representative case studies reveals that a very good
      approximation of the dominant eigenspace is obtained, while only a minimal amount
      of operations and memory space per iteration step is required.

PMID- 18047414
TI  - Design of continuous attractor networks with monotonic tuning using a symmetry
      principle.
AB  - Neurons that sustain elevated firing in the absence of stimuli have been found in
      many neural systems. In graded persistent activity, neurons can sustain firing at
      many levels, suggesting a widely found type of network dynamics in which networks
      can relax to any one of a continuum of stationary states. The reproduction of
      these findings in model networks of nonlinear neurons has turned out to be
      nontrivial. A particularly insightful model has been the "bump attractor," in
      which a continuous attractor emerges through an underlying symmetry in the
      network connectivity matrix. This model, however, cannot account for data in
      which the persistent firing of neurons is a monotonic -- rather than a bell
      shaped -- function of a stored variable. Here, we show that the symmetry used in
      the bump attractor network can be employed to create a whole family of continuous
      attractor networks, including those with monotonic tuning. Our design is based on
      tuning the external inputs to networks that have a connectivity matrix with
      Toeplitz symmetry. In particular, we provide a complete analytical solution of a
      line attractor network with monotonic tuning and show that for many other
      networks, the numerical tuning of synaptic weights reduces to the computation of
      a single parameter.

PMID- 18047413
TI  - A-type K(+) current can act as a trigger for bursting in the absence of a slow
      variable.
AB  - Models of bursting in single cells typically include two subsystems with
      different timescales. Variations in one or more slow variables switch the system
      between a silent and a spiking state. We have developed a model for bursting in
      the pituitary lactotroph that does not include any slow variable. The model
      incorporates fast, noninactivating calcium and potassium currents (the spike
      generating mechanism), as well as the fast, inactivating A-type potassium current
      (I(A)). I(A) is active only briefly at the beginning of a burst, but this brief
      impulse of I(A) acts as a burst trigger, injecting the spike trajectory close to
      an unstable steady state. The spiraling of the trajectory away from the steady
      state produces a period of low-amplitude spiking typical of lactotrophs.
      Increasing the conductance of A-type potassium current brings the trajectory
      closer to the unstable steady state, increasing burst duration. However, this
      also increases interburst interval, and for larger conductance values, all
      activity stops. To our knowledge, this is the first example of a physiologically
      based, single-compartmental model of bursting with no slow subsystem.

PMID- 18047415
TI  - A preliminary analysis of within-subject variation in human serum oxidative
      stress parameters as a function of time.
AB  - The aim of this study was to determine variability at both levels of two serum
      oxidative stress markers (lipid peroxides and carbonyl concentration) as well as
      total antioxidant capacity in humans as a function of time. Assays for oxidative
      stress and antioxidant capacity were repeated in the same individuals three times
      daily on four particular days over a period of 51 days. The results show a high
      variation within subject in the concentration of these markers not only when
      comparing the different days (the morning values can change up to 98%), but also
      during the day, where the evening values can increase up to 84% with respect to
      those of the morning. This suggests that several measurements are required to
      establish the typical oxidative stress status of an individual before studying
      the potential effect of treatments that possibly influence oxidative damage. The
      observed changes during the day allowed us to speculate about the optimum
      temporal antioxidant delivery regimes that minimize the imbalance between
      oxidants and antioxidants. In the study, only a few general aspects of basic
      lifestyle habits were controlled. However, the levels of these markers are
      sensitive to possibly a group of factors. This points to the necessity of using a
      much bigger population to establish the possible contribution of each lifestyle
      habits to the concentration of the markers.

PMID- 18047416
TI  - Anti-apoptotic effect of sphingosine-1-phosphate and platelet-derived growth
      factor in human embryonic stem cells.
AB  - Human embryonic stem (hES) cells hold great promise for use in regenerative
      medicine. However, technologies first need to be established to maintain hES
      cells efficiently in vitro. Understanding the signaling networks involved in hES
      cell maintenance will prove to be essential to the development of such culture
      systems. Previously, we described a serum-free medium capable of supporting
      prolonged hES cell maintenance using sphingosine-1-phosphate (S1P) and platelet
      derived growth factor (PDGF). Here, we describe an anti-apoptotic effect of S1P
      and PDGF in hES cells and demonstrate a direct effect of S1P in preventing hES
      cell apoptosis. Western blot analysis shows that S1P stimulates the
      phosphorylation of the mitogen-activated protein (MAP) kinases Erk1/2 but not of
      Akt, whereas PDGF stimulates both Erk1/2 and Akt phosphorylation. Moreover, our
      study suggests that the Erk1/2 and PI3K/Akt signaling pathways act independently
      of each other. Furthermore, neither S1P nor PDGF modify intracellular calcium
      concentration ([Ca(2+)]( i )) and Smad2 phosphorylation. Using pharmacological
      inhibitors of Erk1/2 and PI3K, our results demonstrate a critical role of the
      Erk1/2 and PI3K/Akt signaling pathways in mediating the anti-apoptotic effect of
      S1P and PDGF on hES cells. However, inhibition of the mammalian target of
      rapamycin (mTOR), a common downstream effector of Erk1/2 and PI3K/Akt, has no
      effect on hES cell apoptosis.

PMID- 18047417
TI  - Elements of a neural stem cell niche derived from embryonic stem cells.
AB  - Recent studies show that adult neural tissues can harbor stem cells within unique
      niches. In the mammalian central nervous system, neural stem cell (NSC) niches
      have been identified in the dentate gyrus and the subventricular zone (SVZ). Stem
      cells in the well-characterized SVZ exist in a microenvironment established by
      surrounding cells and tissue components, including transit-amplifying cells,
      neuroblasts, ependymal cells, blood vessels, and a basal lamina. Within this
      microenvironment, stem cell properties, including proliferation and
      differentiation, are maintained. Current NSC culture techniques often include the
      addition of molecular components found within the in vivo niche, such as
      mitogenic growth factors. Some protocols use bio-scaffolds to mimic the physical
      growth environment of living tissue. We describe a novel NSC culture system,
      derived from embryonic stem (ES) cells, that displays elements of an NSC niche in
      the absence of exogenously applied mitogens or complex physical scaffolding.
      Mouse ES cells were neuralized with retinoic acid and plated on an entactin
      collagen-laminin-coated glass surface at high density (250,000 cells/cm(2)). Six
      to eight days after plating, complex multicellular structures consisting of
      heterogeneous cell types developed spontaneously. NSC and progenitor cell
      proliferation and differentiation continued within these structures. The identity
      of cellular and molecular components within the cultures was documented using RT
      PCR, immunocytochemistry, and neurosphere-forming assays. We show that ES cells
      can be induced to form structures that exhibit key properties of a developing NSC
      niche. We believe this system can serve as a useful model for studies of
      neurogenesis and stem cell maintenance in the NSC niche as well as for
      applications in stem cell transplantation.

PMID- 18047418
TI  - Alpha10 integrin expression is up-regulated on fibroblast growth factor-2-treated
      mesenchymal stem cells with improved chondrogenic differentiation potential.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells that have the capacity to
      differentiate into various different cell lineages and can generate bone,
      cartilage and adipose tissue. MSCs are presently characterized using a broad
      range of different cell-surface markers that are not exclusive to MSCs and not
      sensitive to culture conditions or differentiation capacity. We show that the
      integrin subunits alpha10 and alpha11 of the collagen binding integrins
      alpha10beta1 and alpha11beta1 are expressed by human MSCs in monolayer cultures.
      We also demonstrate that the expression of alpha10 increases, while alpha1 and
      alpha11 decrease, during aggregate culture of MSCs in chondrogenic medium.
      Alpha10beta1 is expressed by chondrocytes in cartilage, whereas alpha11beta1
      integrins are predominantly expressed by subsets of the fibroblastic lineage. In
      extensive monolayer cultures of MSCs, alpha10 expression is down-regulated. We
      show that this down-regulation is reversed by fibroblast growth factor-2 (FGF-2)
      treatment. Addition of FGF-2 to MSCs not only results in increased alpha10
      expression, but also in decreased alpha11 expression. FGF-2 treatment of MSCs has
      been shown to keep the cells more multipotent and also induces cell proliferation
      and Sox-9 up-regulation. We demonstrate improved chondrogenecity as well as
      increased collagen-dependant migratory potential of FGF-2-treated MSCs having a
      high alpha10 expression. We also demonstrate expression of alpha10 and alpha11
      integrin subunits in the endosteum and periosteum of mice, but very low or not
      detectable expression levels in freshly aspired human or mouse BM. We show that
      MSCs with high chondrogenic differentiation potential are highly alpha10 positive
      and propose alpha10 as a potential marker to predict the differentiation state of
      MSCs.

PMID- 18047419
TI  - Evaluation of heart rate variability indices using a real-time handheld remote
      ECG monitor.
AB  - Studies on retrospective electrocardiogram (ECG) recordings of patients during
      cardiac arrest have shown significant changes in heart rate variability (HRV)
      indices prior to the onset of cardiac arrhythmia. The early detection of these
      changes in HRV indices increases the chances for a successful medical
      intervention by increasing the response time window. A portable, handheld remote
      ECG monitor designed in this research detects the QRS complex and calculates
      short-term HRV indices in real-time. The QRS detection of the ECG recordings of
      subjects from the MIT-Arrhythmia database yielded a mean sensitivity of 99.34%
      and a specificity of 99.31%. ECG recordings from normal subjects and subjects
      with congestive heart failure were used to identify the differences in HRV
      indices. An increase in heart rate, high-frequency spectral power (HFP), total
      spectral power, the ratio of HFP to low-frequency spectral power (LFP), and a
      decrease in root mean square sum of RR differences were observed. No difference
      was found on comparison of the standard deviation of normal to normal interval
      between adjacent R-waves, LFP, and very-low-frequency spectral power. Based on
      these, additional analytical calculations could be made to provide early warnings
      of impending cardiac conditions.

PMID- 18047420
TI  - Assessing physician job satisfaction and mental workload.
AB  - Physician job satisfaction and mental workload were evaluated in a pilot study of
      five physicians engaged in a telemedicine practice at The University of Texas
      Medical Branch at Galveston Electronic Health Network. Several previous studies
      have examined physician satisfaction with specific telemedicine applications;
      however, few have attempted to identify the underlying factors that contribute to
      physician satisfaction or lack thereof. One factor that has been found to affect
      well-being and functionality in the workplace-particularly with regard to human
      interaction with complex systems and tasks as seen in telemedicine-is mental
      workload. Workload is generally defined as the "cost" to a person for performing
      a complex task or tasks; however, prior to this study, it was unexplored as a
      variable that influences physician satisfaction. Two measures of job satisfaction
      were used: The Job Descriptive Index and the Job In General scales. Mental
      workload was evaluated by means of the National Aeronautics and Space
      Administration Task Load Index. The measures were administered by means of Web
      based surveys and were given twice over a 6-month period. Nonparametric
      statistical analyses revealed that physician job satisfaction was generally high
      relative to that of the general population and other professionals. Mental
      workload scores associated with the practice of telemedicine in this environment
      are also high, and appeared stable over time. In addition, they are commensurate
      with scores found in individuals practicing tasks with elevated information
      processing demands, such as quality control engineers and air traffic
      controllers. No relationship was found between the measures of job satisfaction
      and mental workload.

PMID- 18047421
TI  - N-glycomic changes in serum proteins during human aging.
AB  - N-glycan profiling of the human serum glycoproteins including immunoglobulin
      fraction on different age groups of healthy persons shows substantial changes
      with increasing age in three major N-glycan structures. In individuals more than
      40-50 years of age, there is an increase in under-galactosylated glycans and a
      decrease in the core alpha-1,6-fucosylated bi-galactosylated biantennary
      structure. These three glycan structures are also substantially changed in a
      Werner syndrome patient, to a level comparable or even more pronounced than those
      observed in a healthy Italian centenarian population. These data show that the
      glycosylation machineries in both liver cells and B-cells are affected in a
      similar way by the aging process despite their highly different nature. The
      observed changes in the glycan structures are indicative that biosynthetic
      processes are at the basis of the changes, possibly together with changes in
      serum clearing of glycan-altered proteins. Our data suggest that measurement of
      the N-glycan level changes could provide a noninvasive surrogate marker for
      general health or for age-related disease progression, and for monitoring the
      improvement of health after therapy.

PMID- 18047422
TI  - Unusual association of Hashimoto's thyroiditis with autoimmune hepatitis.

PMID- 18047423
TI  - Graves' disease with intractable diarrhea, chylous ascites, and chylothorax: a
      case report.
AB  - A 50-year-old woman was admitted to our hospital because of severe diarrhea,
      irritableness, and severe pitting edema of the legs. The patient had been well
      until 5 years before admission, when a tremor and tachycardia developed and a
      diagnosis of Graves' disease was made. Treatment with methimazole was effective
      in reducing her tremor and tachycardia; however, she was often nonadherent with
      her antithyroid medication because of improvement of her symptoms. On admission,
      a thyroid swelling, exophthalmos, a pleural effusion, and ascites were observed.
      The results of thyroid function tests (free triiodothyronine: 21.5 pg/mL; free
      thyroxine: 7.17 ng/dL; thyroid-stimulating hormone (TSH): <0.01 microIU/mL; TSH
      receptor antibodies: 95.9%) were consistent with Graves' disease. Biochemical
      analysis of pleural and ascitic fluid was consistent with chylothorax and chylous
      ascites, respectively. Serum calcium, total protein, and albumin were very low.
      Her symptoms and signs except severe diarrhea, edema, pleural effusion, and
      ascites disappeared after receiving intravenous drip infusion of fluid
      replacement, and methimazole and iodine. Because of malnutrition, she was given a
      high-calorie intravenous infusion. Three months after admission, her pleural
      effusion and ascites began to improve, as did her diarrhea and hypoalbuminemia.
      An appropriate treatment of Graves' disease is crucial to avoid serious sequelae
      of longstanding, poorly controlled hyperthyroidism.

PMID- 18047424
TI  - Algorithms to distinguish the role of gene-conversion from single-crossover
      recombination in the derivation of SNP sequences in populations.
AB  - Meiotic recombination is a fundamental biological event and one of the principal
      evolutionary forces responsible for shaping genetic variation within species. In
      addition to its fundamental role, recombination is central to several critical
      applied problems. The most important example is "association mapping" in
      populations, which is widely hoped to help find genes that influence genetic
      diseases (Carlson et al., 2004; Clark, 2003). Hence, a great deal of recent
      attention has focused on problems of inferring the historical derivation of
      sequences in populations when both mutations and recombinations have occurred. In
      the algorithms literature, most of that recent work has been directed to single
      crossover recombination. However, gene-conversion is an important, and more
      common, form of (two-crossover) recombination which has been much less
      investigated in the algorithms literature. In this paper, we explicitly
      incorporate gene-conversion into discrete methods to study historical
      recombination. We are concerned with algorithms for identifying and locating the
      extent of historical crossing-over and gene-conversion (along with single
      nucleotide mutation), and problems of constructing full putative histories of
      those events. The novel technical issues concern the incorporation of gene
      conversion into recently developed discrete methods (Myers and Griffiths, 2003;
      Song et al., 2005) that compute lower and upper-bound information on the amount
      of needed recombination without gene-conversion. We first examine the most
      natural extension of the lower bound methods from Myers and Griffiths (2003),
      showing that the extension can be computed efficiently, but that this extension
      can only yield weak lower bounds. We then develop additional ideas that lead to
      higher lower bounds, and show how to solve, via integer-linear programming, a
      more biologically realistic version of the lower bound problem. We also show how
      to compute effective upper bounds on the number of needed single-crossovers and
      gene-conversions, along with explicit networks showing a putative history of
      mutations, single-crossovers and gene-conversions. Both lower and upper bound
      methods can handle data with missing entries, and the upper bound method can be
      used to infer missing entries with high accuracy. We validate the significance of
      these methods by showing that they can be effectively used to distinguish
      simulation-derived sequences generated without gene-conversion from sequences
      that were generated with gene-conversion. We apply the methods to recently
      studied sequences of Arabidopsis thaliana, identifying many more regions in the
      sequences than were previously identified (Plagnol et al., 2006), where gene
      conversion may have played a significant role. Demonstration software is
      available at www.csif.cs.ucdavis.edu/~gusfield.

PMID- 18047425
TI  - Statistical estimation of statistical mechanical models: helix-coil theory and
      peptide helicity prediction.
AB  - Analysis of biopolymer sequences and structures generally adopts one of two
      approaches: use of detailed biophysical theoretical models of the system with
      experimentally-determined parameters, or largely empirical statistical models
      obtained by extracting parameters from large datasets. In this work, we
      demonstrate a merger of these two approaches using Bayesian statistics. We adopt
      a common biophysical model for local protein folding and peptide configuration,
      the helix-coil model. The parameters of this model are estimated by statistical
      fitting to a large dataset, using prior distributions based on experimental data.
      L(1)-norm shrinkage priors are applied to induce sparsity among the estimated
      parameters, resulting in a significantly simplified model. Formal statistical
      procedures for evaluating support in the data for previously proposed model
      extensions are presented. We demonstrate the advantages of this approach
      including improved prediction accuracy and quantification of prediction
      uncertainty, and discuss opportunities for statistical design of experiments. Our
      approach yields a 39% improvement in mean-squared predictive error over the
      current best algorithm for this problem. In the process we also provide an
      efficient recursive algorithm for exact calculation of ensemble helicity
      including sidechain interactions, and derive an explicit relation between homo-
      and heteropolymer helix-coil theories and Markov chains and (non-standard) hidden
      Markov models respectively, which has not appeared in the literature previously.

PMID- 18047426
TI  - A decomposition theory for phylogenetic networks and incompatible characters.
AB  - Phylogenetic networks are models of evolution that go beyond trees, incorporating
      non-tree-like biological events such as recombination (or more generally
      reticulation), which occur either in a single species (meiotic recombination) or
      between species (reticulation due to lateral gene transfer and hybrid
      speciation). The central algorithmic problems are to reconstruct a plausible
      history of mutations and non-tree-like events, or to determine the minimum number
      of such events needed to derive a given set of binary sequences, allowing one
      mutation per site. Meiotic recombination, reticulation and recurrent mutation can
      cause conflict or incompatibility between pairs of sites (or characters) of the
      input. Previously, we used "conflict graphs" and "incompatibility graphs" to
      compute lower bounds on the minimum number of recombination nodes needed, and to
      efficiently solve constrained cases of the minimization problem. Those results
      exposed the structural and algorithmic importance of the non-trivial connected
      components of those two graphs. In this paper, we more fully develop the
      structural importance of non-trivial connected components of the incompatibility
      and conflict graphs, proving a general decomposition theorem (Gusfield and
      Bansal, 2005) for phylogenetic networks. The decomposition theorem depends only
      on the incompatibilities in the input sequences, and hence applies to many types
      of phylogenetic networks, and to any biological phenomena that causes pairwise
      incompatibilities. More generally, the proof of the decomposition theorem exposes
      a maximal embedded tree structure that exists in the network when the sequences
      cannot be derived on a perfect phylogenetic tree. This extends the theory of
      perfect phylogeny in a natural and important way. The proof is constructive and
      leads to a polynomial-time algorithm to find the unique underlying maximal tree
      structure. We next examine and fully solve the major open question from Gusfield
      and Bansal (2005): Is it true that for every input there must be a fully
      decomposed phylogenetic network that minimizes the number of recombination nodes
      used, over all phylogenetic networks for the input. We previously conjectured
      that the answer is yes. In this paper, we show that the answer in is no, both for
      the case that only single-crossover recombination is allowed, and also for the
      case that unbounded multiple-crossover recombination is allowed. The latter case
      also resolves a conjecture recently stated in (Huson and Klopper, 2007) in the
      context of reticulation networks. Although the conjecture from Gusfield and
      Bansal (2005) is disproved in general, we show that the answer to the conjecture
      is yes in several natural special cases, and establish necessary combinatorial
      structure that counterexamples to the conjecture must possess. We also show that
      counterexamples to the conjecture are rare (for the case of single-crossover
      recombination) in simulated data.

PMID- 18047427
TI  - Really significant genes for autoimmune thyroid disease do not exist--so how can
      we predict disease?

PMID- 18047428
TI  - Association between decreased WWOX protein expression and thyroid cancer
      development.
AB  - CONTEXT: Chromosomal fragile sites are often related to cancer development. The
      WW domain-containing oxidoreductase gene (WWOX) spans the second most common
      chromosomal fragile site (FRA16D) and encodes an important proapoptotic protein.
      OBJECTIVE: To verify our hypothesis that underexpression of WWOX could contribute
      to malignant transformation of the thyroid cells. METHOD: We compared WWOX
      expression among follicular adenomas (FAs) and differentiated thyroid carcinomas
      [follicular thyroid carcinomas (FTCs) and papillary thyroid carcinomas (PTCs)] in
      53 thyroid tumors resected from patients submitted to total thyroidectomy.
      DESIGN: Multiple fields of tumor areas of FAs, FTCs, and PTCs as well as normal
      thyroid tissue were stained with WWOX antiserum, and classified by the extent of
      staining (percentage of cells staining) and staining intensity. MAIN OUTCOME:
      PTCs showed a significantly decreased expression of WWOX when compared to FAs and
      FTCs. Further, using a unique model of comparison in patients in whom FAs and
      PTCs were concomitantly present, we detected the same result (i.e., no expression
      in PTCs). CONCLUSION: We conclude that WWOX underexpression is an important step
      that might increase the vulnerability to the carcinogenesis process in PTCs.

PMID- 18047429
TI  - Cardiovascular risk in elderly hypothyroid patients.
AB  - Overt hypothyroidism (OH) and subclinical hypothyroidism (SH) are frequently
      found in the elderly. OH is associated with several functional cardiovascular
      abnormalities and increased risk of atherosclerosis resulting from hypertension
      associated to atherogenic lipid profile. Other potential atherogenic factors
      involved in OH are increased circulating C-reactive protein and homocysteine,
      increased arterial stiffness, endothelial dysfunction, and altered coagulation
      parameters. Similar (although mild) cardiovascular abnormalities are present in
      SH. Since all these abnormalities regress with levothyroxine (L-T4)
      administration, the cardiovascular benefits of replacement therapy in OH are not
      questionable, independently from the patient's age or the presence of coexisting
      cardiovascular disease. On the other hand, in spite of a very large number of
      studies, no consensus has been reached so far about the actual cardiovascular
      and/or general health impact of SH, and different recommendations have been
      recently made about screening and treatment of this condition. Although divergent
      results have been obtained in several epidemiological studies, recent meta
      analyses provide evidence for a slight but significant increase of coronary heart
      disease (CHD) risk in SH. However, no agreement has been reached in favor or
      against active screening and/or treatment of mild thyroid failure. Moreover, L-T4
      therapy is discouraged in aged subjects, because the increased oxygen consumption
      consequent to thyroid hormone administration could be dangerous, especially in
      the presence of coexisting CHD. In keeping with this concept are recent data
      showing reduced mortality risk in untreated mild hypothyroid subjects aged >85
      years, suggesting that some degree of decreased thyroid activity at the tissue
      level might have favorable effects in the oldest-old. However, the effects of
      subtle thyroid dysfunction may be different in different age ranges. Since the
      main studies supporting a role for SH as a risk factor for atherosclerosis,
      cardiovascular disease, and all-cause mortality have been carried out in
      populations aged > or =55-60 years, mild thyroid failure could concur to
      increased cardiovascular risk in middle-aged and "young elderly" subjects, while
      being devoid of detrimental effects and possibly protective in the oldest-old.
      Further studies are needed to confirm this hypothesis.

PMID- 18047430
TI  - Clinical features and therapeutic implication of papillary thyroid
      microcarcinoma.
AB  - Papillary thyroid microcarcinomas (PTMs) are small tumors (< or =1 cm of
      diameter) that belong to the well-differentiated low-risk carcinomas of the
      thyroid, which are characterized by benign behavior, probably of little clinical
      significance, and do not affect patients' survival. They are found in otherwise
      normal thyroids or in multinodular goiters with a clinical frequency varying
      substantially according to different series. Sometimes, PTM may be associated
      with lymph node metastases at presentation and/or locoregional recurrences during
      follow-up. Distant metastases are extremely rare, but have been reported.
      Although deaths related to PTM are almost unknown, PTM raises therapeutic
      implications. This review addresses the issue of definition, treatment, and
      follow-up of PTM.

PMID- 18047431
TI  - Treatment of micropapillary carcinoma of the thyroid: where do we draw the line?
AB  - Two patients with papillary thyroid cancer were seen in consultation after they
      had been treated in other medical centers. Their cancers measured 1 and 1.2 mm,
      respectively. Both patients were treated by two thyroid operations and (131)I
      ablation. We believe that, apart from lobectomy, these therapies were not
      justified. We draw attention to this to provide a topic for debate and to attempt
      to prevent this happening to other patients.

PMID- 18047432
TI  - The effect of type of delivery and povidone-iodine application at delivery on
      cord dried-blood-specimen thyrotropin level and the rate of hyperthyrotropinemia
      in mature and normal-birth-weight neonates residing in an iodine-replete area:
      report of Tehran Province, 1998-2005.
AB  - OBJECTIVE: To evaluate the effects of delivery type and of povidone-iodine
      disinfection at delivery on cord dried-blood-specimen (DBS) thyrotropin (TSH)
      concentrations. METHODS: From 1998 to 2005, cord DBSs were collected from live
      deliveries in Tehran and Damavand, and TSH was assayed by a two-site
      immunoradiometric assay. Hyperthyrotropinemia was defined as TSH > or =20 mU/L.
      Vaginal deliveries prepared with povidone-iodine (VGL-PVP-I) or chlorhexidine
      (VGL-CHL), and cesarean sections prepared with povidone-iodine (CS-PVP-I)
      disinfection were assessed. Full-term, normal-size newborns were included. Iodine
      concentrations were measured in urine samples collected from 132 pregnant women
      immediately prior to delivery. RESULTS: Median (range) TSH was 5.3 (1.0 to >100)
      mU/L in VGL-PVP-I (n = 23,432), 5.3 (1.0 to >100) mU/L in VGL-CHL (n = 5658), and
      5.0 (1.0 to >100) mU/L in CS-PVP-I (n = 19,016) (p < 0.0001). Median TSH was
      higher in VGL-PVP-I versus CS-PVP-I (p < 0.0001) and in VGL-CHL versus CS-PVP-I
      (p < 0.0001). Hyperthyrotropinemia was present in 1.4%, 1.2%, and 0.8% of VGL-PVP
      I, VGL-CHL, and CS-PVP-I deliveries, respectively, and was significantly higher
      in VGL-PVP-I versus CS-PVP-I (p < 0.0001) and in VGL-CHL versus CS-PVP-I (p =
      0.005). Median (range) urinary iodine concentration of pregnant women was 176 (20
      4600) microg/L. CONCLUSION: Cord DBS TSH and rates of hyperthyrotropinemia are
      lower in cesarean section than in vaginal deliveries. Povidone-iodine
      disinfection at delivery has an effect neither on DBS TSH concentrations nor on
      the rate of hyperthyrotropinemia in the iodine-replete area of Iran.

PMID- 18047433
TI  - Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine
      Society Clinical Practice Guideline.

PMID- 18047435
TI  - The effect of subsequent pregnancy on patients with thyroid carcinoma apparently
      free of the disease.

PMID- 18047437
TI  - A note on Lewicki-Sejnowski gradient for learning overcomplete representations.
AB  - Overcomplete representations have greater robustness in noise environment and
      also have greater flexibility in matching structure in the data. Lewicki and
      Sejnowski (2000) proposed an efficient extended natural gradient for learning the
      overcomplete basis and developed an overcomplete representation approach.
      However, they derived their gradient by many approximations, and their proof is
      very complicated. To give a stronger theoretical basis, we provide a brief and
      more rigorous mathematical proof for this gradient in this note. In addition, we
      propose a more robust constrained Lewicki-Sejnowski gradient.

PMID- 18047438
TI  - The use of CranioSacral therapy in a physically impaired population in a
      disability service in southern Ireland.

PMID- 18047439
TI  - Duckweed (Lemna gibba L.) as a test organism for homeopathic potencies.
AB  - OBJECTIVES: A bioassay with duckweed (Lemna gibba L.) was used to study the
      effects of homeopathic potencies on the plant's growth rate. Screening included
      12 substances: argentum nitricum, copper sulfate, gibberellic acid, 3-indole
      acetic acid, kinetin, lactose, lemna minor, methyl jasmonate, metoxuron,
      phosphorus, potassium nitrate, and sulfur. Each substance was tested in the
      potency range 14x-30x. Controls were unsuccussed and succussed water. DESIGN: In
      randomized and blinded experiments, duckweed was grown in either potentized
      substances or water controls over 7 days. Frond (leaf) growth was measured
      regularly with a computerized image analysis system and growth rates were
      calculated for different time intervals (day 0-7, 0-3, 3-7). Additionally, a
      water control run with unsuccussed water as the only test substance was performed
      to determine the variability of the bioassay. RESULTS: For the water control run,
      the between-group coefficient of variance for groups of five replicates was 0.87%
      for the frond area-related average specific growth rate r(area) compared to 1.60%
      for the frond number-related average specific growth rate r(num). Thus, the
      former is the preferred parameter to be used. Of twelve tested substances,
      potentized argentum nitricum, phosphorus, and kinetin significantly (p<0.05,
      analysis of variance F-test) affected the main parameter: frond area-related
      average specific growth rate (day 0-7). Segmented area growth rates (day 0-3 or 3
      7) were affected by potentized argentum nitricum, gibberellic acid, lactose, and
      phosphorus. CONCLUSIONS: The described experimental set-up with L. gibba as test
      organism appears to be a promising new model system to investigate effects of
      potentized substances. Yet larger sets of replication experiments with selected
      test substances and systematic negative controls are necessary to verify the
      effects found.

PMID- 18047440
TI  - Assessing the utility of the standards for reporting trials of acupuncture
      (STRICTA): a survey of authors.
AB  - OBJECTIVE: To inform the potential revision of Standards for Reporting
      Interventions in Controlled Trials of Acupuncture (STRICTA), we sought the
      opinion of acupuncture trial authors and systematic reviewers to rank the utility
      of the guidelines and asked trial authors about their experiences using them.
      DESIGN: Questionnaires ranking STRICTA items and qualitative responses about
      experience using the guidelines. SAMPLE: The authors of 38 randomized controlled
      acupuncture trials randomly selected from a systematic search of those published
      in 2004 and 2005 were contacted with a questionnaire. Authors of 14 Cochrane
      acupuncture systematic reviews or protocols published in the same time frame were
      also sent a questionnaire. RESULTS: Fifty-four percent (54%) (28/52) of the
      sample responded. Among the trial authors, 58% (11/19) used STRICTA to help guide
      their writing, but more than half of these reported that the editing process had
      removed some or all of the STRICTA-specific items. STRICTA was seen as a helpful
      reference, but authors requested that some items be clarified. Respondents tended
      to rank the utility of STRICTA highly overall, but five items in particular were
      not highly valued; three of these pertained to details on the trial
      acupuncturists' background. Authors flagged potential difficulties of reporting
      unusual trial designs in the current format of STRICTA. CONCLUSIONS: Authors of
      acupuncture trials and systematic reviews believe that STRICTA contributes to the
      reporting of acupuncture interventions and rate it highly. Because very few
      acupuncture studies are published in STRICTA-adopting journals, the editing
      process for journals unaware of the guidelines may be responsible for deleting
      acupuncture intervention-specific items. Several items remain unclear, and the
      relevance of STRICTA to some trial designs is questioned. A review of STRICTA is
      warranted to clarify and reconsider items, and targeted promotion to non
      complementary and alternative medicine journals should be considered.

PMID- 18047441
TI  - Measuring dimensions of body connection: body awareness and bodily dissociation.
AB  - OBJECTIVE: This study aimed to test the preliminary psychometric properties of
      the Scale of Body Connection (SBC), a 20-item self-report measure, designed to
      assess body awareness and bodily dissociation in mind-body intervention research.
      METHODS: The SBC items were based on common expressions of awareness in body
      therapy. Content validity was established by a panel of experts. The validity and
      reliability of the scale was examined with an undergraduate sample. To assess the
      scale's discriminant validity, the respondents were asked to indicate exposure to
      specific traumas. RESULTS: Confirmatory factor analysis, used to examine the
      scale's construct validity, indicated acceptable goodness-of-fit indices, and
      revealed uncorrelated subscales, reflecting independent dimensions. Cronbach's
      alpha revealed equal internal consistency reliability for each subscale for both
      men and women. Body awareness scores did not differ between individuals with and
      without reported trauma exposure. Bodily dissociation scores differed between
      individuals with and without past experience with physical trauma, suggesting the
      applicability of this subscale for use with populations with trauma histories.
      CONCLUSIONS: The results provide preliminary evidence of the construct validity
      and internal consistency reliability of the SBC.

PMID- 18047442
TI  - Can electrons act as antioxidants? A review and commentary.
AB  - A previous study demonstrated that connecting the human body to the earth during
      sleep (earthing) normalizes the daily cortisol rhythm and improves sleep. A
      variety of other benefits were reported, including reductions in pain and
      inflammation. Subsequent studies have confirmed these earlier findings and
      documented virtually immediate physiologic and clinical effects of grounding or
      earthing the body. It is well established, though not widely known, that the
      surface of the earth possesses a limitless and continuously renewed supply of
      free or mobile electrons as a consequence of a global atmospheric electron
      circuit. Wearing shoes with insulating soles and/or sleeping in beds that are
      isolated from the electrical ground plane of the earth have disconnected most
      people from the earth's electrical rhythms and free electrons. The most
      reasonable hypothesis to explain the beneficial effects of earthing is that a
      direct earth connection enables both diurnal electrical rhythms and free
      electrons to flow from the earth to the body. It is proposed that the earth's
      diurnal electrical rhythms set the biological clocks for hormones that regulate
      sleep and activity. It is also suggested that free electrons from the earth
      neutralize the positively charged free radicals that are the hallmark of chronic
      inflammation. A relationship between cortisol and inflammation was established in
      the pioneering work of H. Selye published in the 1950s. Current biomedical
      research has led to an inflammation hypothesis that is establishing chronic
      inflammation as the culprit behind almost every modern chronic illness. The
      research summarized here and in subsequent reports provides a basis for a number
      of earthing technologies that restore and maintain natural electrical contact
      between the human body and the earth throughout the day and night in situations
      where going barefoot on the earth is impractical. It is proposed that free or
      mobile electrons from the earth can resolve chronic inflammation by serving as
      natural antioxidants.

PMID- 18047443
TI  - Seeking an oracle: using the Delphi process to develop practice guidelines for
      the treatment of endometriosis with Chinese herbal medicine.
AB  - BACKGROUND: For most complementary and alternative medicine interventions, the
      absence of a high-quality evidence base to define good practice presents a
      serious problem for clinicians, educators, and researchers. The Delphi process
      may offer a pragmatic way to establish good practice guidelines until more
      rigorous forms of assessment can be undertaken. OBJECTIVES: To use a modified
      Delphi to develop good practice guidelines for a feasibility study exploring the
      role of Chinese herbal medicine (CHM) in the treatment of endometriosis. To
      compare the outcomes from Delphi with data derived from a systematic review of
      the Chinese language database. DESIGN: An expert group was convened for a three
      round Delphi that initially produced key statements relating to the CHM diagnosis
      and treatment of endometriosis (round 1) and then anonymously rated these on a 1
      7 Likert scale (rounds 2 and 3). Statements with a median score of 5 and above
      were regarded as demonstrating positive group consensus. The differential
      diagnoses within Chinese Medicine and rating of the clinical value of individual
      herbs were then contrasted with comparable data from a review of Chinese language
      reports in the Chinese Biomedical Retrieval System (1978-2002), and China Academy
      of Traditional Chinese Medicine (1985-2002) databases and the Chinese TCM and
      magazine literature (1984-2004) databases. RESULTS: Consensus (good practice)
      guidelines for the CHM treatment of endometriosis relating to common diagnostic
      patterns, herb selection, dosage, and patient management were produced. The
      Delphi guidelines demonstrated a high degree of congruence with the information
      from the Chinese language databases. CONCLUSIONS: In the absence of rigorous
      evidence, Delphi offers a way to synthesize expert knowledge relating to
      diagnosis, patient management, and herbal selection in the treatment of
      endometriosis. The limitations of the expert group and the inability of Delphi to
      capture the subtle nuances of individualized clinical decision-making limit the
      usefulness of this approach.

PMID- 18047444
TI  - Gymnema sylvestre for diabetes mellitus: a systematic review.
AB  - Across the globe, there are an estimated 150 million people suffering from
      diabetes mellitus. Each of these people is at increased risk of developing a
      number of complications, each of which are associated with a reduction in quality
      of life and an increase in individual morbidity and mortality. However, despite
      these psychosocial implications, as well as the financial burden associated with
      the management of the disease, existing treatment options are costly, and have
      limited, palliative effects. One treatment that is emerging as a potential
      panacea for the management of diabetes is Gymnema sylvestre. Yet, what evidence
      is there to support the use of this extract? In order to answer this question, a
      systematic review of the literature and a discussion of the best available
      evidence on gymnema are needed. The findings of such a review are presented in
      this paper.

PMID- 18047445
TI  - Herbal mixtures containing the mushroom Ganoderma lucidum improve recovery time
      in patients with herpes genitalis and labialis.
AB  - OBJECTIVE: To investigate the time course for resolution of symptoms from
      recurrent herpes simplex viral infections after treatment with the herbal mixture
      WTTCGE [Wisteria floribunda, Trapa natans, Terminalia chebulae, Coicis lachryma
      jobi, Ganoderma lucidum, Elfuinga applanata]. METHODS: Fifteen (15) patients with
      herpes genitalis (49.3+/-12.0: mean+/-standard deviation age in years), and 13
      patients with herpes labialis (43.7+/-12.9), were studied. All had been suffering
      from recurrent herpes outbreaks for more than 1 year, and had received regular
      outpatient treatment at other medical institutions without improvement. RESULTS:
      The herbal mixture, WTTCGE appeared to provide fast, effective relief from the
      symptoms of recurrent herpes genitalis and labialis. The mean duration before
      relief from herpes genitalis occurred was 10.9+/-6.3 days without WTTCGE
      treatment and 4.9+/-1.3 days with it (p<0.002). Similarly, the time required to
      obtain relief from herpes labialis was 7.8+/-4.3 days without WTTCGE treatment
      and 4.0+/-1.1 days with it (p<0.005). CONCLUSIONS: Administration of WTTCGE to
      patients suffering from herpes genitalis and labialis appears to shorten the time
      required to obtain symptom relief as has been shown in a previous report.

PMID- 18047446
TI  - Who uses complementary and alternative medicine in Israel?
AB  - OBJECTIVE: To describe the Israeli complementary and alternative medicine users
      and examine whether they are the same or different from non-users. DESIGN: This
      analysis was conducted on data collected from the use of health services module
      (n=2,365) of the Israeli National Health Interview Survey conducted 2003-2004.
      The questionnaire was based on the European Health Interview Survey and was
      administered over the telephone by trained interviewers. SUBJECTS: This survey
      was conducted on a random sample of the Israel general population age 21 years or
      more. OUTCOME MEASURES: Chi-square tests and logistic regression analyses were
      conducted. Complementary and alternative medicine was defined as self-reported
      use of homeopath, acupuncturist, chiropractor/osteopath, naturopath, or other
      complementary and alternative provider services for the subjects' own health
      needs in the last 12 months. RESULTS: Almost 6 percent of Israelis reported using
      complementary and alternative medicine. Use increased with income. Users were
      more likely to visit any doctor or a specialist in the prior 4 weeks to the
      survey compared to nonusers. Users self-reported similar use of pain medications
      compared to nonusers. CONCLUSIONS: These findings inform the international debate
      regarding if and how complementary and alternative medicine services should be
      covered by national health insurance.

PMID- 18047447
TI  - Use of complementary and alternative therapies in community-dwelling older
      adults.
AB  - OBJECTIVES: Although complementary and alternative medicine (CAM) use is becoming
      increasingly prevalent in the United States, knowledge regarding complementary
      and alternative therapy use in older adults is limited. The purposes of this
      study were to (1) assess the prevalence and patterns of CAM use in a probability
      based sample of older adults; (2) describe the characteristics of older CAM
      users; and (3) identify factors associated with complementary and alternative
      medicine use/nonuse. METHODS: A cross-sectional survey design was used. An age
      stratified sample of community-dwelling adults ages>or=65 (N=1200) was randomly
      selected from the Minnesota Driver's License/Identification Tape using names from
      the Twin Cities seven-county metropolitan area. The mailed questionnaire included
      items on demographics, health status, health care utilization, CAM modality use,
      reasons for use, costs, and complementary and alternative therapy use
      satisfaction. Descriptive statistics, chi-square tests, and regression analysis
      were performed. RESULTS: Overall, 62.9% (N=445) of the respondents reported use
      of one or more complementary and alternative medicine modalities with an average
      of three modalities (SD+/-1.9, range 1-11). The top five CAM modalities used were
      nutritional supplements (44.3%), spiritual healing/prayer (29.7%), megavitamins
      (28.3%), herbal supplements (20.7%), and chiropractic (17.8%). Maintaining health
      and treating a health condition were the primary reasons for CAM use. The most
      common conditions treated were arthritis (44.4%) and chronic pain (23.5%).
      Demographic variables were not significantly different between CAM users and
      nonusers. CAM users reported more unhealthy days than nonusers did. Overall
      satisfaction with CAM use was high (80%). Symptoms of a health problem and desire
      for personal control over health motivated CAM use. The main barriers to CAM use
      were lack of reason to use and knowledge about CAM. Only 53% of users disclosed
      CAM use to their primary care providers. CONCLUSIONS: CAM use is common in older
      adults, especially those with health problems. The widespread use of oral
      supplements combined with not disclosing CAM use to primary care providers is a
      concern.

PMID- 18047448
TI  - Turkish general practitioners and complementary/alternative medicine.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is in the spotlight of
      society. However, what is the position of physicians at this point? OBJECTIVES:
      To determine general practitioners' (GP) knowledge, attitudes, and approaches to
      CAM. METHODS: All GPs (n=521) practicing in Bursa Province, Turkey were surveyed
      by a questionnaire. RESULTS: Responses from 49% of GPs were analyzed. Altogether,
      most of our physicians (96.5%) had not received any education about CAM, wanted
      to learn more (74.4%), and their knowledge levels were low (60.8%). About half of
      them (51%) believed in the efficiency of CAM, whereas 38.0% did not. GPs desire
      more information about herbal medicine and acupuncture. Only 29% of GPs were
      using some type of CAM for themselves. CONCLUSIONS: GPs are aware of the
      subject's importance and want to learn more about CAM and improve their
      knowledge. It would be reasonable to provide training possibilities for GPs,
      primarily for the CAM types highly used by the population and most requested by
      the physicians.

PMID- 18047449
TI  - Utilization of Ayurveda in health care: an approach for prevention, health
      promotion, and treatment of disease. Part 1--Ayurveda, the science of life.
AB  - Ayurveda is a natural health care system that originated in India more than 5000
      years ago. Its main objective is to achieve optimal health and well-being through
      a comprehensive approach that addresses mind, body, behavior, and environment.
      Ayurveda emphasizes prevention and health promotion, and provides treatment for
      disease. It considers the development of consciousness to be essential for
      optimal health and meditation as the main technique for achieving this. Treatment
      of disease is highly individualized and depends on the psychophysiologic
      constitution of the patient. There are different dietary and lifestyle
      recommendations for each season of the year. Common spices are utilized in
      treatment, as well as herbs and herbal mixtures, and special preparations known
      as Rasayanas are used for rejuvenation, promotion of longevity, and slowing of
      the aging process. A group of purification procedures known as Panchakarma
      removes toxins from the physiology. Whereas Western allopathic medicine is
      excellent in handling acute medical crises, Ayurveda demonstrates an ability to
      manage chronic disorders that Western medicine has been unable to. It may be
      projected from Ayurveda's comprehensive approach, emphasis on prevention, and
      ability to manage chronic disorders that its widespread use would improve the
      health status of the world's population.

PMID- 18047450
TI  - Response to a proposal for an integrative medicine curriculum.
AB  - BACKGROUND: A paper entitled "Core Competencies in Integrative Medicine for
      Medical School Curricula: A proposal," published in Academic Medicine, stimulated
      a broad discussion among complementary and alternative medicine (CAM) educators.
      This discussion led to a formal process for responding to the issues raised by
      the paper. METHODS: Representatives from the Academic Consortium for
      Complementary and Alternative Health Care (ACCAHC) and the Oregon Collaborative
      for Complementary and Integrative Medicine (OCCIM) formed the ACCAHC/OCCIM Task
      Force to participate in a Delphi process of consultation and deliberation. This
      process led to a broad, cross-discipline agreement on important points to include
      in a response to the integrative medicine (IM) curriculum proposal. RESULTS: Five
      key areas of concern emerged: (1) the definition of IM as presented in the paper;
      (2) lack of clarity about the goals of the proposed IM curriculum; (3) lack of
      recognition of the breadth of whole systems of health care; (4) omission of
      competencies related to collaboration between MDs and CAM professionals in
      patient care; and (5) omission of potential areas of partnership in IM education.
      CONCLUSIONS: A major overall theme emerging from the Delphi process was a desire
      for closer collaboration between conventional medical schools and CAM academic
      institutions in developing IM curricula. Several cross-disciplinary venues for
      addressing the Delphi Task Force themes include the National Center for
      Complementary and Alternative Medicine's R-25 Initiatives, and the National
      Education Dialogue. OCCIM is presented as an example of a successful lateral
      integration approach.

PMID- 18047451
TI  - Evaluation of internet websites marketing herbal weight-loss supplements to
      consumers.
AB  - OBJECTIVE: The aim of this study was to evaluate the quality and quantity of drug
      information available to consumers on Internet websites marketing herbal weight
      loss dietary supplements in the United States. METHODS: We conducted an Internet
      search using the search engines Yahoo and Google and the keywords "herbal weight
      loss." Website content was evaluated for the presence of active/inactive
      ingredient names and strengths and other Food and Drug Administration (FDA)
      labeling requirements. Information related to drug safety for the most common
      herbal ingredients in the products evaluated was compared against standard herbal
      drug information references. RESULTS: Thirty-two (32) websites were evaluated for
      labeling requirements and safety information. All sites listed an FDA disclaimer
      statement and most sites (84.4%) listed active ingredients, although few listed
      strengths or inactive ingredients. Based on the drug information for the most
      common ingredients found in the weight-loss dietary supplements evaluated,
      potential contraindications for cardiovascular conditions, pregnancy/nursing, and
      high blood pressure were listed most frequently (73%, 65.5%, and 37%,
      respectively), whereas few websites listed potential drug interactions or adverse
      reactions. CONCLUSIONS: Potential hazards posed by dietary supplements may not be
      accurately, if at all, represented on Internet websites selling these products.
      Since consumers may not approach their physicians or pharmacists for information
      regarding use of dietary supplements in weight loss, it becomes necessary for
      health care providers to actively engage their patients in open discussion
      regarding the use, benefits, and hazards of dietary supplements.

PMID- 18047455
TI  - Qualitative research is evidence, too.

PMID- 18047456
TI  - Short-term effects on outcomes related to the mechanism of intervention and
      physiological outcomes but insufficient evidence of clinical benefits for
      breathing control: a systematic review.
AB  - QUESTIONS: What is the volume, quality, consistency, and generalisability of the
      evidence for breathing control? What is the effect on outcomes related to the
      target and mechanism of breathing control, as well as physiological and clinical
      outcomes? DESIGN: Systematic review with meta-analysis. PARTICIPANTS: People with
      chronic respiratory disease, post-surgical, or asymptomatic individuals.
      INTERVENTION: Breathing control (relaxed basal, diaphragmatic, or abdominal
      breathing) as the sole intervention. OUTCOME MEASURES: All outcome measures
      providing continuous data. RESULTS: Twenty studies were included within the meta
      analysis. A beneficial effect was found for abdominal movement (SMD 1.36, 95% CI
      0.42 to 2.31), diaphragm excursion (SMD 1.39, 95% CI 1.00 to 1.77), respiratory
      rate (SMD -0.84, 95% CI -1.09 to -0.60), tidal volume (SMD 0.98, 95% CI 0.71 to
      1.25), arterial oxygen saturation (SMD 0.63, 95% CI 0.25 to 1.02) and
      percutaneous oxygen (SMD 1.48, 95% CI 0.85 to 2.11). Breathing control had a
      detrimental effect on the work of breathing (SMD 1.06, 95% CI 0.52 to 1.60) and
      dyspnoea (SMD 1.47, 95% CI 0.88 to 2.05). CONCLUSION: When used as a sole
      intervention, there was a beneficial effect on outcomes related to the mechanism
      of breathing control as well as on short-term physiological outcomes. In people
      with severe respiratory disease, breathing control resulted in a detrimental
      effect on dyspnoea and work of breathing. There was no clear evidence of an
      effect on ventilation or long-term physiological outcomes related to gas exchange
      or the energy cost of breathing. Overall, evidence was satisfactory with studies
      demonstrating poor consistency, good generalisability, and satisfactory volume
      and quality.

PMID- 18047457
TI  - A predominantly home-based progressive resistance exercise program increases knee
      extensor strength in the short-term in people with chronic obstructive pulmonary
      disease: a randomised controlled trial.
AB  - QUESTIONS: Does a 12-week, predominantly home-based program of progressive
      resistance exercises reduce impairments, activity limitations, and participation
      restrictions in people with chronic obstructive pulmonary disease? Are any gains
      maintained 12 weeks after the cessation of the program? DESIGN: Randomised
      controlled trial with concealed allocation, assessor blinding, and intention-to
      treat analysis. PARTICIPANTS: 54 people with moderately severe chronic
      obstructive pulmonary disease not undergoing pulmonary rehabilitation.
      INTERVENTION: The experimental group performed six progressive resistance
      exercises three times per week (once a week hospital-based, twice a week home
      based) for 12 weeks. Exercise intensity was three sets of 8 to 12 repetition
      maximum progressed against elasticised bands of increasing resistance. The
      control group received no intervention. OUTCOME MEASURES: Primary outcomes were
      strength (knee extensor, hip abductor, shoulder horizontal flexor, shoulder
      flexor) measured using hand-held dynamometry, and walking capacity measured by
      the 6-minute Walk Test performed before and after intervention and again at 12
      weeks after the cessation of intervention. RESULTS: The experimental group
      increased their knee extensor strength by 4.9 kg (95% CI 1.1 to 8.7) more than
      the control group by Week 12. However, this gain was not maintained at Week 24.
      No difference between the groups was found for any of the other primary outcomes.
      CONCLUSIONS: A predominantly home-based progressive resistance exercise program
      led to modest improvements in knee extensor strength in people with chronic
      obstructive pulmonary disease. However, 44% of the experimental group were unable
      to complete the exercise program, highlighting the need to understand factors
      influencing adherence to exercise in this population.

PMID- 18047458
TI  - Four weeks of daily stretch has little or no effect on wrist contracture after
      stroke: a randomised controlled trial.
AB  - QUESTIONS: In adults undergoing rehabilitation after stroke, does 30 minutes of
      daily stretch of the wrist and finger flexors for four weeks prevent or reverse
      contracture, decrease pain, or improve upper-limb activity? Are any gains
      maintained one week and five weeks after the cessation of stretching? DESIGN:
      Randomised controlled trial with concealed randomisation, assessor blinding, and
      intention-to-treat analysis. PARTICIPANTS: 40 adults undergoing rehabilitation
      after stroke or stroke-like brain injury, who were unable to actively extend the
      affected wrist. INTERVENTION: Both groups received routine upper-limb retraining
      five days a week. In addition, the experimental group received 30 minutes daily
      stretch of the wrist and finger flexors five days a week for four weeks. OUTCOME
      MEASURES: The primary outcome was contracture, measured as torque-controlled
      passive wrist extension with the fingers extended. Secondary outcomes were pain
      at rest measured on a 10-cm visual analogue scale, and upper-limb activity
      measured using the Motor Assessment Scale. Outcomes were collected at baseline,
      post-intervention, and one and five weeks after cessation of intervention.
      RESULTS: The mean effect on passive range of wrist extension was 3.8 [corrected]
      degrees (95% CI -2.5 to 10.1) [corrected] after 4 weeks of daily stretch, 4.1
      degrees (95% CI -4.0 to 12.3) after a week of no stretch, and 3.5 degrees (95% CI
      -4.6 to 11.7) after a further four weeks. CONCLUSION: These data suggest that
      four weeks of regular stretching has little or no effect on wrist contracture
      after stroke. However the estimate of the size of this effect is not sufficiently
      precise to rule out the possibility of a marginally worthwhile effect. The
      stretch had no significant effect on upper-limb pain, and did not result in
      significantly improved upper-limb activity.

PMID- 18047459
TI  - Cyclic pneumatic soft-tissue compression enhances recovery following fracture of
      the distal radius: a randomised controlled trial.
AB  - QUESTIONS: Does the addition of cyclic pneumatic soft-tissue compression during
      the 6-week immobilisation period following fracture of the distal radius result
      in a faster recovery of muscle strength and joint range of motion? Does it result
      in a larger recovery of muscle strength and joint range of motion immediately
      after the immobilisation period (at 6 weeks) or four weeks after the
      immobilisation period (at 10 weeks)? DESIGN: Randomised controlled trial with
      concealed allocation and assessor blinding. PARTICIPANTS: 21 patients with
      fracture of the distal radius. INTERVENTION: The experimental group received
      cyclic pneumatic soft-tissue compression during the 6-week immobilisation period
      whereas the control group received usual care. Both groups were instructed to
      actively make a fist 100 times per day during the 6-week immobilisation period
      and were given an exercise program during the 4-week post-immobilisation period.
      OUTCOME MEASURES: Function was measured as power grip, pinch grip, key grip, and
      supination strength using dynamometry from Week 1 to 10 as well as wrist
      flexion/extension and forearm supination/pronation range of motion using
      goniometry from Week 6 to 10. The outcome measures are presented as a percentage
      of the intact side. RESULTS: The experimental group improved significantly faster
      than the control group in muscle strength from Week 1 to 10 (p ? 0.001) but not
      in joint range of motion from Week 6 to 10 (p > 0.05). By Week 6, the
      experimental group was 12-26% stronger and had 8-14% more range of motion than
      the control group. By Week 10, the experimental group was 24-29% stronger and had
      10-15% more range of motion than the control group. CONCLUSION: The findings
      indicate that a larger clinical trial is warranted and should incorporate direct
      measures of fracture healing.

PMID- 18047460
TI  - Trunk stabilisation exercises reduce sternal separation in chronic sternal
      instability after cardiac surgery: a randomised cross-over trial.
AB  - QUESTION: Do trunk stabilisation exercises reduce sternal separation and pain,
      and improve the quality and control of the performance of tasks in individuals
      with chronic sternal instability? DESIGN: Randomised crossover study with
      concealed allocation and intention-to-treat analysis. PARTICIPANTS: Nine
      individuals with chronic sternal instability following a median sternotomy for
      cardiac surgery. INTERVENTION: The experimental intervention consisted of six
      weeks of trunk stabilisation exercises; the control intervention was no
      exercises. OUTCOME MEASURES: Outcomes were sternal separation measured by
      ultrasound in mm, pain during the performance of nine everyday tasks measured on
      a 100-mm visual analogue scale, and the quality and control of the performance of
      two tasks scored on a 100-mm visual analogue scale. RESULTS: Overall, sternal
      separation during the period of trunk stabilisation exercises decreased by 6.2 mm
      (95% CI 3.5 to 8.9) more than during the control period. Overall, pain decreased
      when performing everyday tasks by 14 mm (95% CI 5 to 23) more than during the
      control period. Overall, task performance during the period of trunk
      stabilisation exercises did not improve (mean difference 10 mm, 95% CI -3 to 22)
      more than during the control period. CONCLUSION: Trunk stabilisation exercises
      should be included in the rehabilitation of individuals who experience sternal
      instability following cardiac surgery. A larger trial is warranted to determine
      if stabilisation exercises are beneficial in improving the quality and control of
      task performance.

PMID- 18047461
TI  - Physiotherapy decision making in acute cardiorespiratory care is influenced by
      factors related to physiotherapist and the nature and context of the decision: a
      qualitative study.
AB  - QUESTIONS: What factors influence the decision making of cardiorespiratory
      physiotherapists in acute care? How do cardiorespiratory physiotherapists manage
      multiple factors in their decision making? DESIGN: Qualitative study using
      observation and semi-structured interviews. PARTICIPANTS: Fourteen
      physiotherapists working in acute cardiorespiratory care. RESULTS:
      Cardiorespiratory physiotherapy decision making was affected by factors related
      to the nature of the decision itself (such as the complexity and difficulty of
      the decision), factors related to the context in which the decision occurred
      (such as physical, organisational and socio-professional factors), and factors
      related to the physiotherapists themselves (such as decision making capabilities,
      physiotherapy frames of reference, and level of clinical experience). CONCLUSION:
      Optimising the quality of decision making in the context of health care today
      requires an awareness and consideration of a range of factors influencing
      decision making.

PMID- 18047462
TI  - Clinical prediction rules can be derived and validated for injured Australian
      workers with persistent musculoskeletal pain: an observational study.
AB  - QUESTIONS: Can clinical prediction rules be derived for injured Australian
      workers with persistent musculoskeletal pain? Are they valid? DESIGN:
      Longitudinal observational study. PARTICIPANTS: 847 injured workers with
      persistent musculoskeletal pain undergoing rehabilitation. OUTCOME MEASURES: At
      baseline, 12 putative predictors were measured. At 9 weeks, short-term outcomes
      such as pain (visual analogue scale), activity limitation (Functional Rating
      Index) and work upgrade (increase in work hours or duties) were measured. At 6
      months, long-term work status (working or not working) was measured. RESULTS:
      Data were obtained from 85% of the participants who were followed up at both 9
      weeks (720 of 847) and 6 months (247 of 290). Predictors of outcome included high
      baseline pain and activity limitation, long duration of previous intervention,
      not working, non-English speaking background, and the area of pain. Accuracy was
      highest for clinical prediction rules predicting pain and level of activity
      limitation at 9 weeks (R2 = 0.67 and 0.69 respectively) and work status at 6
      months (LR- = 0.24). CONCLUSION: Accurate clinical prediction rules have been
      derived and validated for injured workers with persistent musculoskeletal pain,
      predicting activity limitation, pain, and work outcomes following exercise-based
      rehabilitation. Further research to validate these prediction rules in other
      populations and to assess the effectiveness of tailoring intervention based on
      the estimated prognosis would be valuable.

PMID- 18047463
TI  - Physiotherapy in intensive care is safe: an observational study.
AB  - QUESTION: How often do adverse events (including adverse physiological changes)
      occur during physiotherapy intervention in intensive care? DESIGN: A multi-centre
      prospective observational study. PARTICIPANTS: Five tertiary level university
      affiliated intensive care units. OUTCOME MEASURES: All physiotherapy intervention
      in five intensive care units over a three month period. When certain specified
      changes occurred during physiotherapy intervention, details were noted including
      diagnosis of patient, intervention, vital signs, radiological changes, co
      morbidities, chemical pathology, and fluid balance. RESULTS: 12 281 physiotherapy
      interventions were completed with 27 interventions resulting in adverse
      physiological changes (0.2%). This incidence was significantly lower than a
      previous study of adverse physiological changes (663 events in 247 patients over
      a 24-hour period); the incidence during physiotherapy intervention was lower than
      during general intensive care. Common factors in the patients who had an adverse
      physiological change were a deterioration in cardiovascular status (ie, decrease
      in blood pressure or arrhythmia) in patients on medium to high doses of
      inotropes/vasopressors, unstable baseline hemodynamic values, previous cardiac co
      morbidities and intervention consisting of positive pressure or right side lying.
      CONCLUSION: The incidence of adverse events during physiotherapy intervention in
      these five tertiary hospitals was low, demonstrating that physiotherapy
      intervention in intensive care is safe.

PMID- 18047464
TI  - Clinical networks--bridging the research-quality chasm.

PMID- 18047465
TI  - Mechanisms underlying developmental programming of elevated blood pressure and
      vascular dysfunction: evidence from human studies and experimental animal models.
AB  - Cardiovascular-related diseases are the leading cause of death in the world in
      both men and women. In addition to the environmental and genetic factors, early
      life conditions are now also considered important contributing elements to these
      pathologies. The concept of 'fetal' or 'developmental' origins of adult diseases
      has received increased recognition over the last decade, yet the mechanism by
      which altered perinatal environment can lead to dysfunction mostly apparent in
      the adult are incompletely understood. This review will focus on the mechanisms
      and pathways that epidemiological studies and experimental models have revealed
      underlying the adult cardiovascular phenotype dictated by the perinatal
      experience, as well as the probable key causal or triggering elements. Programmed
      elevated blood pressure in the adult human or animal is characterized by vascular
      dysfunction and microvascular rarefaction. Developmental mechanisms that have
      been more extensively studied include glucocorticoid exposure, the role of the
      kidneys and the renin-angiotensin system. Other pathophysiological pathways have
      been explored, such as the role of the brain and the sympathetic nervous system,
      oxidative stress and epigenetic changes. As with many complex diseases, a
      unifying hypothesis linking the perinatal environment to elevated blood pressure
      and vascular dysfunction in later life cannot be presumed, and a better
      understanding of those mechanisms is critical before clinical trials of
      preventive or 'deprogramming' measures can be designed.

PMID- 18047466
TI  - Vitamin A: a drug for prevention of restenosis/reocclusion after percutaneous
      coronary intervention?
AB  - The re-establishment of adequate blood flow in a vessel with a reduced lumen due
      to an atherosclerotic plaque by percutaneous vascular intervention is a well
      established procedure. However, the long-term outcome of such interventions is
      negatively influenced by the development of intimal hyperplasia/restenosis.
      Although extensively researched, this still represents a significant clinical
      problem. Retinoids, i.e. natural and synthetic derivates of vitamin A, represent
      a potential therapeutic compound, since they have been shown to influence the
      vast majority of processes that ultimately lead to reocclusion of the injured
      vessel. Retinoids exert their effects at the transcriptional level through their
      nuclear receptors. Targeting multiple processes, i.e. proliferation, migration,
      extracellular matrix composition and cell differentiation, as well as
      coagulation/fibrinolysis, should increase their future role in the prevention of
      restenosis. The purpose of this review is to summarize the diverse effects of
      retinoids on pathobiological and biological processes activated at sites of
      vascular injury with particular emphasis on intimal hyperplasia/restenosis after
      endovascular interventions.

PMID- 18047467
TI  - Cell (patho)physiology of magnesium.
AB  - There is an unsettled debate about the role of magnesium as a 'chronic regulator'
      of biological functions, as opposed to the well-known role for calcium as an
      'acute regulator'. New and old findings appear to delineate an increasingly
      complex and important role for magnesium in many cellular functions. This review
      summarizes the available evidence for a link between the regulation of
      intracellular magnesium availability and the control of cell growth, energy
      metabolism and death, both in healthy and diseased conditions. A comprehensive
      view is precluded by technical difficulties in tracing magnesium within a
      multicompartment and dynamic environment like the cell; nevertheless, the last
      few years has witnessed encouraging progress towards a better characterization of
      magnesium transport and its storage or mobilization inside the cell. The latest
      findings pave the road towards a new and deeper appreciation of magnesium
      homoeostasis and its role in the regulation of essential cell functions.

PMID- 18047469
TI  - Post-transcriptional regulation of CLMP mRNA is controlled by tristetraprolin in
      response to TNFalpha via c-Jun N-terminal kinase signalling.
AB  - During spermatogenesis, extensive restructuring of blood-testis barrier takes
      place to facilitate the migration of preleptotene/leptotene spermatocytes from
      the basal to the adluminal compartment in the seminiferous epithelium. However,
      the biochemical mechanisms involved in this event remain elusive. Recent studies
      have shown that pro-inflammatory cytokine TNFalpha (tumour necrosis factor alpha)
      plays a crucial role in this event by inhibiting the expression of tight junction
      proteins in Sertoli cells. In the present study, we sought to examine the
      detailed mechanism on how TNFalpha affects the expression of CLMP (coxsackie- and
      adenovirus-receptor-like membrane protein), a newly identified tight junction
      transmembrane protein, in the testis. Addition of TNFalpha (10 ng/ml) to Sertoli
      cell culture (TM4 cells) significantly reduced the steady-state CLMP mRNA and
      protein levels. In an mRNA stability assay, it was shown that the rate of CLMP
      mRNA degradation was significantly increased when cells treated with TNFalpha
      were compared with vehicle. Blockage of the JNK (c-Jun N-terminal kinase)
      signalling pathway by SP600125 significantly abolished the TNFalpha-mediated
      destabilization of CLMP mRNA. Activation of the JNK signalling pathway by
      TNFalpha up-regulated the expression of an RNA-binding protein, TTP
      (tristetraprolin). TTP was present in the RNA-protein complex in the RNA EMSA
      (electrophoretic mobility shift assay) and decreased the CLMP 3'-UTR
      (untranslated region)-dependent luciferase activity. Taken together, these
      results suggest that the TNFalpha-mediated mRNA degradation of the CLMP gene is
      controlled by TTP through the JNK signalling cascade.

PMID- 18047470
TI  - n-Propyl gallate activates hypoxia-inducible factor 1 by modulating intracellular
      oxygen-sensing systems.
AB  - HIF-1 (hypoxia-inducible factor 1) is a master regulator of cellular adaptive
      responses to hypoxia. The expression and transcriptional activity of the HIF
      1alpha subunit is stringently controlled by intracellular oxygen tension through
      the action of prolyl and asparaginyl hydroxylases. In the present study we
      demonstrate that PG (n-propyl gallate) activates HIF-1 and expression of its
      downstream target genes under normoxic conditions in cultured cells and in mice.
      The stability and transcriptional activity of HIF-1alpha are increased by PG. PG
      treatment inhibits the interaction between HIF-1alpha and VHL (von Hippel-Lindau
      protein) and promotes the interaction between HIF-1alpha and p300, indicating
      that PG inhibits the activity of both prolyl and asparaginyl HIF-1alpha
      hydroxylases. We conclude that PG activates HIF-1 and enhances the resultant gene
      expression by directly affecting the intracellular oxygen sensing system in vitro
      and in vivo and that PG represents a lead compound for the development of a non
      toxic activator of HIF-1.

PMID- 18047468
TI  - Is the mineralocorticoid receptor a potential target for stroke prevention?
AB  - In recent years, it has become increasingly clear that the extra-renal effects of
      aldosterone play an important role in the pathogenesis of cardiovascular disease.
      Stroke is one of the leading causes of death in the Western world, and MR
      (mineralocorticoid receptor) antagonism is a potential preventative therapy for
      patients at risk of both ischaemic and haemorrhagic strokes. This protective
      effect of MR antagonism appears to occur at the level of the cerebral vasculature
      and may be related to the expression and activation of the EGFR (epidermal growth
      factor receptor) and the degree of vessel wall collagen deposition.

PMID- 18047471
TI  - A novel bivalent single-chain variable fragment (scFV) inhibits the action of
      tumour necrosis factor alpha.
AB  - Suppression of TNFalpha (tumour necrosis factor alpha) activity is widely
      considered to be among the most efficient treatments available for chronic
      inflammatory diseases. Here, a bivalent scFv (single-chain variable fragment)
      fragment, named TNF-BAb, was engineered by fusing two anti-TNFalpha scFV
      fragments in tandem via a long and flexible linking peptide derived from human
      serum albumin and produced in functional form from Escherichia coli inclusion
      bodies. The bioactivity assays demonstrated that TNF-BAb gained enormously in
      avidity and showed a much stronger ability to inhibit the biological action of
      TNFalpha, indicating that TNF-BAb may become a good candidate for anti-TNFalpha
      therapy.

PMID- 18047472
TI  - ARL2, ARG1 and PIN3 define a gravity signal transduction pathway in root
      statocytes.
AB  - ALTERED RESPONSE TO GRAVITY1 (ARG1) and its paralog ARG1-LIKE2 (ARL2) are J
      domain proteins that are required for normal root and hypocotyl gravitropism. In
      this paper, we show that both ARL2 and ARG1 function in a gravity signal
      transduction pathway with PIN3, an auxin efflux facilitator that is expressed in
      the statocytes. In gravi-stimulated roots, PIN3 relocalizes to the lower side of
      statocytes, a process that is thought to, in part, drive the asymmetrical
      redistribution of auxin toward the lower flank of the root. We show that ARL2 and
      ARG1 are required for PIN3 relocalization and asymmetrical distribution of auxin
      upon gravi-stimulation. ARL2 is expressed specifically in the root statocytes,
      where it localizes to the plasma membrane. Upon ectopic expression, ARL2 is also
      found at the cell plate of dividing cells during cytokinesis, an area of intense
      membrane dynamics. Mutations in ARL2 and ARG1 also result in auxin-related
      expansion of the root cap columella, consistent with a role for ARL2 and ARG1 in
      regulating auxin flux through the root tip. Together these data suggest that ARL2
      and ARG1 functionally link gravity sensation in the statocytes to auxin
      redistribution through the root cap.

PMID- 18047473
TI  - The xenobiotic beta-aminobutyric acid enhances Arabidopsis thermotolerance.
AB  - The non-protein amino acid beta-aminobutyric acid (BABA) primes Arabidopsis to
      respond more quickly and strongly to pathogen and osmotic stress. Here, we report
      that BABA also significantly enhances acquired thermotolerance in Arabidopsis.
      This thermotolerance was dependent on heat shock protein 101, a critical
      component of the normal heat-shock response. BABA did not enhance basal
      thermotolerance under a severe heat-shock treatment. No roles for the hormones
      ethylene and salicylic acid in BABA-induced acquired thermotolerance were
      identified by mutant analysis. Using global gene expression analysis, transcript
      levels for several transcription factors and DNA binding proteins regulating
      responses to the stress hormone abscisic acid (ABA) were found to be elevated in
      BABA-treated plants compared with water-treated plants. The role of ABA in BABA
      induced thermotolerance was complex. BABA-enhanced thermotolerance was partially
      compromised in the ABA-insensitive mutant, abi1-1, but was augmented in abi2-1.
      In an unrelated process, BABA, like ABA, inhibited root growth, and the level of
      inhibition was roughly additive in roots treated with both compounds. Root growth
      of both abi1-1 and abi2-1 was also inhibited by BABA. Unexpectedly, abi1-1 and
      abi2-1 root growth was inhibited more strongly by combined ABA and BABA
      treatments than by BABA alone. Our results, together with previously published
      data, suggest that BABA is a general enhancer of plant stress resistance, and
      that cross-talk occurs between BABA and ABA signalling cascades. Specifically,
      the BABA-mediated accumulation of ABA transcription factors without concomitant
      activation of a downstream ABA response could represent one component of the BABA
      primed state in Arabidopsis.

PMID- 18047474
TI  - Phytochrome-mediated inhibition of shade avoidance involves degradation of growth
      promoting bHLH transcription factors.
AB  - Plant growth and development are particularly sensitive to changes in the light
      environment and especially to vegetational shading. The shade-avoidance response
      is mainly controlled by the phytochrome photoreceptors. In Arabidopsis, recent
      studies have identified several related bHLH class transcription factors (PIF,
      for phytochrome-interacting factors) as important components in phytochrome
      signaling. In addition to a related bHLH domain, most of the PIFs contain an
      active phytochrome binding (APB) domain that mediates their interaction with
      light-activated phytochrome B (phyB). Here we show that PIF4 and PIF5 act early
      in the phytochrome signaling pathways to promote the shade-avoidance response.
      PIF4 and PIF5 accumulate to high levels in the dark, are selectively degraded in
      response to red light, and remain at high levels under shade-mimicking
      conditions. Degradation of these transcription factors is preceded by
      phosphorylation, requires the APB domain and is sensitive to inhibitors of the
      proteasome, suggesting that PIF4 and PIF5 are degraded upon interaction with
      light-activated phyB. Our data suggest that, in dense vegetation, which is rich
      in far-red light, shade avoidance is triggered, at least partially, as a
      consequence of reduced phytochrome-mediated degradation of transcription factors
      such as PIF4 and PIF5. Consistent with this idea, the constitutive shade
      avoidance phenotype of phyB mutants partially reverts in the absence of PIF4 and
      PIF5.

PMID- 18047475
TI  - Acute acetaminophen overdose is associated with dose-dependent hypokalaemia: a
      prospective study of 331 patients.
AB  - Hypokalaemia is a recognized complication of acute acetaminophen overdose. It is
      unclear whether this might be a pharmacological effect of acetaminophen, or due
      to association with confounding factors. The present study sought to better
      characterize the relationship between acetaminophen concentrations and risk of
      hypokalaemia. A prospective study of patients received N-acetylcysteine treatment
      within 15 hr of acute acetaminophen ingestion. Serum potassium concentrations
      were determined before and after N-acetylcysteine. Serum acetaminophen
      concentrations were used to indicate overall drug exposure by comparison to the
      Rumack-Matthew nomogram. Hypokalaemia was pre-defined by serum concentrations
      <3.5 mmol/l, and groups compared by Mann-Whitney tests. There were 331 patients.
      Median (95% confidence interval) fall in serum potassium concentration after N
      acetylcysteine was 0.05 mmol/l (-0.11-0.30 mmol/l) if acetaminophen
      concentrations were below the 'high-risk' treatment line, 0.30 mmol/l (0.17-0.40
      mmol/l) if between the 'high-risk' and 'normal' treatment lines (P = 0.0358), and
      0.40 mmol/l (0.20-0.50 mmol/l) if above the 'normal' treatment line (P = 0.0136).
      A receiver operating characteristic showed that high acetaminophen concentrations
      were predictive of hypokalaemia (P = 0.0001 versus zero discriminatory line), and
      4 hr acetaminophen concentration >156 mmol/l gave 81% sensitivity and 48%
      specificity. The risk of hypokalaemia after acute acetaminophen overdose depends
      on the extent of acetaminophen exposure, irrespective of N-acetylcysteine
      administration and independent of whether vomiting occurred. Acetaminophen
      appears to cause concentration-dependent hypokalaemia after overdose, and the
      pharmacological basis requires further consideration.

PMID- 18047476
TI  - Increased expression of catalase in human hepatoma cells by the soy isoflavone,
      daidzein.
AB  - The reduced incidence of cancer that has been observed in Asian population
      traditionally consuming soy-based food has been linked to the antioxidant
      potential of soy isoflavones, in particular daidzein and genistein. The present
      study was undertaken in order to test the antioxidative potential of daidzein and
      to examine the effect of daidzein treatment on the expression of the antioxidant
      enzyme catalase in the human hepatoma cell lines Huh-7 and HepG2. Daidzein itself
      did not display radical scavenging activity but it significantly increased the
      activity of the antioxidant enzyme catalase. Huh-7 cells were much more
      susceptible to daidzein cytotoxicity than HepG2 cells and showed much lower basal
      activity in luciferase reporter gene assays with the 3.2 kb fragment of the human
      catalase promoter. However, treatment with daidzein at a non-toxic concentration
      resulted in a similar induction of promoter activity in both cell lines. Reporter
      gene studies with different promoter constructs in HepG2 cells restrict the
      potential localization of the main regulatory elements for basal and inducible
      activity of the catalase promoter to a region approximately 120 bp to 300 bp
      upstream of the start codon of the catalase gene. From our results, we conclude
      that in human hepatoma cells daidzein at a non-toxic concentration increases the
      activity of human catalase and induces the transcription of the catalase gene via
      interaction with the proximal part of the promoter.

PMID- 18047477
TI  - Effects of lactational exposure to soy isoflavones on reproductive system in
      neonatal female rats.
AB  - To examine effects of lactational exposure to soy isoflavones on female
      reproductive system, soy isoflavones, 0 (control), 10, 50, 100, 150 or 200 mg/kg
      body weight, were administered to maternal rats by gavage daily during postnatal
      days 5-10. Ten female litters were killed on day 11. Uterine and ovary weights,
      serum oestradiol and progesterone concentrations, proliferating cell nuclear
      antigen, mRNA expressions of oestrogen receptor, androgen receptor and
      progesterone receptor in uterus or ovary were measured. When compared to the
      control group, litters in the 150 and 200 mg/kg body weight groups had
      significantly higher ovary and uterine weights (P < 0.05). Endometrial thickness
      was also significantly increased. Isoflavone-treated groups had increased
      proliferating cell nuclear antigen staining in comparison to the control group.
      Litters in the 50, 150 and 200 mg/kg body weight groups had significantly higher
      oestradiol concentration while lower progesterone concentrations than those in
      the control group (P < 0.05 or P < 0.01). All soy isoflavone-treated groups had
      androgen receptor mRNA expressions in ovary and uterus comparable to the control
      group. Progesterone receptor mRNA expression in the 150 and 200 mg/kg body weight
      groups was significantly lower than that in control group (P < 0.01). However,
      ovaries in the 150 and 200 mg/kg body weight groups had significantly higher
      oestrogen receptor mRNA expression while the uterus in these two treatment groups
      had significantly lower expressions, when compared to the control group (P < 0.05
      or P < 0.01). In conclusion, lactational exposure to isoflavones could result in
      oestrogen-like actions on the reproductive system of neonate female rats, which
      mechanisms may be, at least, involved with modifications of hormone production
      and steroid receptor transcription in the reproductive system.

PMID- 18047478
TI  - The dark side of ecstasy: neuropsychiatric symptoms after exposure to 3,4
      methylenedioxymethamphetamine.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a known neurotoxin in
      animals. This review discusses the history, pattern of use, pharmacology, acute
      and long-term effects of MDMA. Emphasis is given to the concern that MDMA may
      induce long-term cognitive and psychiatric effects. MDMA is an illegal substance,
      and investigations of the effects of exposure in human beings have limitations
      and weaknesses. There are numerous studies suggesting a correlation between MDMA
      exposure and psychopathology, and that the psychotropic effects may be long
      lasting or permanent. However, it is not possible to conclude that there is a
      causal relationship between exposure and the increased psychopathology observed
      in MDMA users. Longitudinal studies are needed to assess whether MDMA causes
      persistent cognitive impairment and/or psychiatric symptoms in human beings.

PMID- 18047479
TI  - Effects of azumolene on normal and malignant hyperthermia-susceptible skeletal
      muscle.
AB  - Malignant hyperthermia is a pharmacogenetic disease of skeletal muscle in which a
      life-threatening, hypermetabolic syndrome is induced by exposure of susceptible
      patients to halogenated general anaesthetics and/or succinylcholine. Dantrolene
      sodium, the only drug effective for treatment of malignant hyperthermia, has low
      water solubility that makes its clinical use difficult. The aim of this study was
      to investigate the potency of azumolene, a 30-fold more water-soluble analogue,
      in comparison to the prototype dantrolene sodium, on mammalian and human skeletal
      muscles. The twitches of extensor digitorum longus and soleus muscles from mice
      were inhibited by azumolene with IC(50) of 2.8 +/- 0.8 and 2.4 +/- 0.6 microM,
      respectively. The IC(50) of dantrolene sodium in these muscles was 1.6 +/- 0.4
      and 3.5 +/- 1.2 microM, respectively, with no difference in comparison to
      azumolene. Previous in vitro exposure of mouse soleus muscle to azumolene and
      dantrolene sodium (10 microM) significantly inhibited 8 mM caffeine-induced
      contractures. Azumolene was just effective as dantrolene sodium in relaxing
      caffeine-induced contractures of mouse soleus muscle. Intravenous injection
      caused dose-dependent decreases in twitches of guinea pig gastrocnemius muscle
      with IC(50) of 1.2 +/- 0.1 and 1.5 +/- 0.2 mg/kg for azumolene and dantrolene
      sodium, respectively. Azumolene, 10 microM, was effective in blocking and
      reversing caffeine-induced contracture of human malignant hyperthermia
      susceptible skeletal muscle in vitro. These studies provide evidence that
      azumolene is equipotent to dantrolene sodium in blocking pharmacologic-induced
      muscle contractures and that azumolene should be efficacious for
      treatment/prevention of malignant hyperthermia.

PMID- 18047480
TI  - Brain activation for alertness measured with functional near infrared
      spectroscopy (fNIRS).
AB  - Alertness is a basic psychological function within the construct of attention.
      The neural basis of alertness has been found in the right frontotemporal cortex
      and the left ventrolateral prefrontal cortex. The aim of the present study was to
      establish the measurement of functional brain activity during alertness with
      functional near infrared spectroscopy (fNIRS). Therefore we measured the changes
      in brain oxygenation in two independent samples during an alertness condition and
      control conditions with 52 NIRS channels placed over the frontotemporal area.
      Based on a region of interest defined in the first sample (and on the literature)
      we showed in the second sample significantly higher activation during the
      alertness condition compared to the control conditions. This study proves the
      possibility of investigating the neural correlates of alertness using fNIRS.

PMID- 18047481
TI  - Dietary sodium effects on heart rate variability in salt sensitivity of blood
      pressure.
AB  - High dietary sodium intake is a risk factor for hypertension, and heart rate
      variability (HRV) is decreased in hypertension. Effects of dietary sodium intake
      on HRV of normotensive persons have not, however, been investigated to date. The
      present study examined effects of low and high sodium diets on blood pressure,
      heart rate, and HRV in 36 healthy, normotensive women, ages 40-70. Each was
      placed on a low sodium diet for 6 days followed by a high sodium diet for 6 days.
      The high salt diet increased mean systolic blood pressure, decreased heart rate,
      and increased high frequency HRV (HF). Cardiac vagal tone, estimated at baseline
      from heart period and a time domain estimate of respiratory sinus arrhythmia, was
      higher in salt-sensitive than salt-insensitive subjects. The finding of increased
      vagal tone in normotensive persons on high salt intake indicates that dietary
      sodium status should be considered in behavioral studies of HRV.

PMID- 18047482
TI  - Novelty and conflict in the categorization of complex stimuli.
AB  - We manipulated categorical typicality and the presence of conflicting information
      as participants categorized multifeatured artificial animals. In Experiment 1,
      rule-irrelevant features were correlated with particular categories during
      training. In the test phase, participants applied a one-dimensional rule to
      stimuli with rule-irrelevant features that were category-congruent, category
      incongruent, or novel. Category-incongruent and novel features delayed RT and P3
      latency, but had no effect on the N2. Experiment 2 used a two-dimensional rule to
      create conflict between rule-relevant features. Conflict resulted in prolonged
      RTs and larger amplitudes of a prefrontal positive component, but had no impact
      on the N2. Stimuli with novel features did elicit a larger N2 than those with
      frequent features. These results suggest limitations on the generality of the
      N2's sensitivity to conflicting information while confirming its sensitivity to
      attended visual novelty.

PMID- 18047483
TI  - Relative left frontal activation to appetitive stimuli: considering the role of
      individual differences.
AB  - Experiments examining asymmetrical frontal activity in response to affective
      pictures have produced inconsistent results. These inconsistencies may have
      occurred because the pictorial stimuli may not have evoked strong emotional or
      motivational tendencies for all individuals. In the current study, participants
      were asked to indicate their liking for dessert and the time since they had last
      eaten to assess individual differences in emotion and motivation. Then, they were
      shown dessert pictures or neutral pictures while EEG activity was recorded.
      Results indicated that the individual differences predicted greater left than
      right frontal activity (inverse of the alpha power) within the first second as
      well as all 12 s of viewing of the dessert pictures.

PMID- 18047484
TI  - EEG correlates of emotions in dream narratives from typical young adults and
      individuals with autistic spectrum disorders.
AB  - The relationship between emotional dream content and Alpha and Beta REM sleep EEG
      activity was investigated in typical individuals and in Autistic Spectrum
      Disorders (ASD). Dream narratives of persons with ASD contained fewer emotional
      elements. In both groups, emotions correlated positively with slow Alpha (8.0
      10.0 Hz) spectral power over parieto-occipital and left central regions, as well
      as with a right occipital EEG asymmetry. Slow Alpha activity in ASD individuals
      was lower over midline and parasagittal areas and higher over lateral areas
      compared to controls. Both groups displayed a right-biased slow Alpha activity
      for midparietal and occipital (significantly higher in control) sites. Results
      indicate that Alpha EEG activity may represent a neurophysiological substrate
      associated with emotional dream content. Distinctive Alpha EEG patterns and
      asymmetries suggest that dream generation implies different brain connectivity in
      ASD.

PMID- 18047485
TI  - Pharmacological and functional characterization of novel EP and DP receptor
      agonists: DP1 receptor mediates penile erection in multiple species.
AB  - INTRODUCTION: Despite the widespread use of prostaglandin E(1) as an efficacious
      treatment for male erectile dysfunction for more than two decades, research on
      prostanoid function in penile physiology has been limited. AIM: To characterize
      the pharmacological and physiological activity of novel subtype-selective EP and
      DP receptor agonists. METHODS: Radioligand binding and second messenger assays
      were used to define receptor subtype specificity of the EP and DP agonists.
      Functional activity was further characterized using isolated human and rabbit
      penile cavernosal tissue in organ baths. In vivo activity was assessed in rabbits
      and rats by measuring changes in cavernous pressure after intracavernosal
      injection of receptor agonists. MAIN OUTCOME MEASURES: Receptor binding and
      signal transduction, smooth muscle contractile activity, erectile function.
      RESULTS: In organ bath preparations of human cavernosal tissue contracted with
      phenylephrine, EP2- and EP4-selective agonists exhibited variable potency in
      causing relaxation. One of the compounds caused mild contraction, and none of the
      compounds was as effective as PGE(1) (EC(50) = 0.23 microM). There was no
      consistent correlation between the pharmacological profile (receptor binding and
      second messenger assays) of the EP agonists and their effect on cavernosal tissue
      tone. In contrast, the DP1-selective agonist AS702224 (EC(50) =29 nM) was more
      effective in relaxing human cavernosal tissue than either PGE(1), PGD(2) (EC(50)
      = 58 nM), or the DP agonist BW245C (EC(50) =59 nM). In rabbit cavernosal tissue,
      PGE(1) and PGD(2) caused only contraction, while AS702224 and BW245C caused
      relaxation. Intracavernosal administration of AS702224 and BW245C also caused
      penile tumescence in rabbits and rats. For each compound, the erectile response
      improved with increasing dose and was significantly higher than vehicle alone.
      CONCLUSIONS: These data suggest that AS702224 is a potent DP1-selective agonist
      that causes penile erection. The DP1 receptor mediates relaxation in human
      cavernosal tissue, and stimulates pro-erectile responses in rat and rabbit. Thus,
      rabbits and rats can be useful models for investigating the physiological
      function of DP1 receptors.

PMID- 18047486
TI  - Effects of written information material on help-seeking behavior in patients with
      erectile dysfunction: a longitudinal study.
AB  - INTRODUCTION: Neither men with erectile dysfunction (ED) nor their physicians are
      willing to discuss sexual problem sufficiently. Written information material
      could facilitate a dialogue and encourage men to seek treatment. AIM: The central
      task of this article was to determine the effectiveness and acceptance of patient
      information material for sexual dysfunction. METHODS: Through an information
      campaign, men received informational material. Eight thousand men also received a
      first survey, which asked about the intention to seek treatment and to discuss
      the sexual problem with a physician or partner. A second follow-up questionnaire,
      3-6 months after the first one, asked for the implementation of these intentions.
      Descriptive and regression-based analyses were applied. MAIN OUTCOME MEASURES:
      Help-seeking behavior, subjective assessment of change in disease severity and
      partnership quality, satisfaction. RESULTS: Four hundred forty-three men
      participated in both surveys. Nearly 90% of them became active after reading the
      information material. More than half talked with their partner (57.8%) and a
      physician (65%), and one-third sought treatment (31.8%). Especially discussing
      the problem with the partner and receiving treatment improved erectile
      functioning and led to an increase in the quality of partnership (P </= 0.05).
      The initial intention to become active was a good predictor for completing an
      action. The main reasons for not becoming active were inhibitions to talk about
      ED (46.8%) and fear of a medical examination (27.7%). CONCLUSIONS: Overall, the
      results demonstrate that written information material is a useful resource for
      men with ED, because it evokes a high help-seeking behavior. It was perceived
      both to improve the sexual problem as well as to increase the quality of
      partnership. Providing such material in the medical practice may be an
      appropriate way to overcome inhibitions and to initiate dialogue with affected
      men. However, the results must be interpreted with caution because of possible
      motivationally driven self-selection bias.

PMID- 18047487
TI  - Modified hygienic Epitec System abutment for magnetic retention of orbital
      prostheses.
AB  - Maintenance of healthy periimplant soft tissue is a significant problem for
      orbital prosthesis wearers. Two female patients with orbital defects after
      malignant tumor resection were treated using custom-made retentive components of
      an individual magnet for an Epitec System orbital prosthesis. Freestanding
      hygienic retentive components for an individual magnet were fabricated. An
      abutment replica was trimmed and modified, and using pattern resin, a magnetic
      keeper was cast and soldered to the abutment. The patients could maintain good
      hygiene and healthy periimplant soft tissue. This type of freestanding retentive
      component may be advantageous for the hygiene maintenance of periimplant soft
      tissue.

PMID- 18047488
TI  - A simple method of positioning the iris disk on a custom-made ocular prosthesis.
      A clinical report.
AB  - We report two cases of ocular prosthesis fabrication that make use of a
      transparent graph grid for positioning the iris disk. The custom-made ocular
      prostheses achieved intimate contact with the tissue bed enabling ideal fit. As
      asymmetry may result in a squint-eyed appearance, proper positioning of the iris
      disk in the scleral wax pattern is vital to fabricating the custom-made
      artificial eye. The position of the iris disk in the custom-made ocular
      prosthesis was in symmetry with that of the natural eye, restoring esthetics of
      the patient.

PMID- 18047489
TI  - Mechanical behavior and failure analysis of prosthetic retaining screws after
      long-term use in vivo. Part 2: Metallurgical and microhardness analysis.
AB  - PURPOSE: This study involved testing and analyzing multiple retrieved prosthetic
      retaining screws after long-term use in vivo to: (1) detect manufacturing defects
      that could affect in-service behavior; (2) characterize the microstructure and
      alloy composition; and (3) further characterize the wear mechanism of the screw
      threads. MATERIALS AND METHODS: Two new (control) screws from Nobel Biocare (NB)
      and 18 used (in service 18-120 months) retaining screws [12 from NB and 6 from
      Sterngold (SG)] were: (1) metallographically examined by light microscopy and
      scanning electron microscopy (SEM) to determine the microstructure; (2) analyzed
      by energy dispersive X-ray (EDX) microanalysis to determine the qualitative and
      semiquantitative average alloy and individual phase compositions; and (3) tested
      for Vickers microhardness. RESULTS: Examination of polished longitudinal sections
      of the screws using light microscopy revealed a significant defect in only one
      Group 4 screw. No significant defects in any other screws were observed. The
      defect was considered a "seam" originating as a "hot tear" during original
      casting solidification of the alloy. Additionally, the examination of
      longitudinal sections of the screws revealed a uniform homogeneous microstructure
      in some groups, while in other groups the sections exhibited rows of second phase
      particles. The screws for some groups demonstrated severe deformation of the
      lower threads and the bottom part of the screw leading to the formation of
      crevices and grooves. Some NB screws were comprised of Au-based alloy with Pt,
      Cu, and Ag as alloy elements, while others (Groups 4 and 19) were Pd-based with
      Ga, Cu, and Au alloy elements. The microstructure was homogeneous with fine or
      equiaxed grains for all groups except Group 4, which appeared inhomogeneous with
      anomalous grains. SG screws demonstrated a typical dendritic structure and were
      Au-based alloy with Cu and Ag alloy elements. There were differences in the
      microhardness of gold alloy screws from NB and SG as well as palladium alloy
      screws from NB. CONCLUSIONS: Significant differences within NB retaining screws
      and between NB and SG screws were found for microstructure, major alloy
      constituents, and microhardness.

PMID- 18047490
TI  - Evaluation of load at fracture of Procera AllCeram copings using different luting
      cements.
AB  - PURPOSE: The current study investigated the effect of different luting agents on
      the fracture resistance of Procera AllCeram copings. METHODS: Six master dies
      were duplicated from the prepared maxillary first premolar tooth using
      nonprecious metal alloy (Wiron 99). Thirty copings (Procera AllCeram) of 0.6-mm
      thickness were manufactured. Three types of luting media were used: zinc
      phosphate cement (Elite), glass ionomer cement (Fuji I), and dual-cured composite
      resin cement (Panavia F). Ten copings were cemented with each type. Two master
      dies were used for each group, and each of them was used to lute five copings.
      All groups were cemented according to manufacturer's instructions and received a
      static load of 5 kg during cementation. After 24 hours of distilled water storage
      at 37 degrees C, the copings were vertically compressed using a universal testing
      machine at a crosshead speed of 1 mm/min. RESULTS: ANOVA revealed significant
      differences in the load at fracture among the three groups (p < 0.001). The
      fracture strength results showed that the mean fracture strength of zinc
      phosphate cement (Elite), glass ionomer cement (Fuji I), and resin luting cement
      (Panavia F) were 1091.9 N, 784.8 N, and 1953.5 N, respectively. CONCLUSION:
      Different luting agents have an influence on the fracture resistance of Procera
      AllCeram copings.

PMID- 18047491
TI  - Excellent early and late outcomes of aortic valve replacement in people aged 80
      and older.
AB  - OBJECTIVES: To investigate early and late outcome of aortic valve replacement
      (AVR) in a large cohort of patients aged 80 and older. DESIGN: Retrospective
      study of consecutive patients undergoing AVR using a computerized database based
      on the New York State Department of Health registry. Data collection was
      performed prospectively. SETTING: University hospital (single institution).
      PARTICIPANTS: One thousand three hundred eight patients undergoing AVR (231
      (17.6%) aged > or = 80, 1,077 (82.4%) < 80). MEASUREMENTS: Patient
      characteristics, hospital mortality, morbidity, length of stay and long-term
      survival were analyzed. RESULTS: Subjects aged 80 and older were more likely to
      be female, had a lower body mass index, and presented significantly more often
      with comorbidities such as heart failure, renal failure, and extensive aortic
      calcification. Crude hospital mortality was 5.2% (n=12) in subjects age 80 and
      older, compared with 4.5% (n=48) in those younger than 80 (P=.37). Respiratory
      failure occurred more frequently in those aged 80 and older. In multivariate
      logistic regression analysis, age of 80 and older was not a predictor of hospital
      mortality. The median length of stay was significantly higher in those aged 80
      and older than in those younger than 80 (10 days vs 7 days, P=.01). Five-year
      survival was 64+/-5% in those aged 80 and older, which was similar to that of the
      age- and sex-matched general U.S. population. CONCLUSION: Excellent results after
      AVR can be expected in patients aged 80 and older, with minimal increase in
      postoperative mortality and acceptable postoperative morbidity. Respiratory
      failure is the main postoperative complication in patients aged 80 and older.
      Recent advances in operative techniques and perioperative management have
      contributed to better surgical outcomes in these patients than found in
      historical reports.

PMID- 18047492
TI  - Antioxidant vitamin supplement use and risk of dementia or Alzheimer's disease in
      older adults.
AB  - OBJECTIVES: To examine whether use of vitamins C or E alone or in combination was
      associated with lower incidence of dementia or Alzheimer's disease (AD). DESIGN:
      Prospective cohort study. SETTING: Group Health Cooperative, Seattle, Washington.
      PARTICIPANTS: Two thousand nine hundred sixty-nine participants aged 65 and older
      without cognitive impairment at baseline in the Adult Changes in Thought study.
      MEASUREMENTS: Participants were followed biennially to identify incident dementia
      and AD diagnosed according to standard criteria. Participants were considered to
      be users of vitamins C or E if they self-reported use for at least 1 week during
      the month before baseline. RESULTS: Over a mean follow-up+/-standard deviation of
      5.5+/-2.7 years, 405 subjects developed dementia (289 developed AD). The use of
      vitamin E was not associated with dementia (adjusted hazard ratio (HR)=0.98, 95%
      confidence interval (CI)=0.77-1.25) or with AD (HR=1.04; 95% CI=0.78-1.39). No
      association was found between vitamin C alone (dementia: HR=0.90, 95% CI=0.71
      1.13; AD: HR=0.95, 95% CI=0.72-1.25) or concurrent use of vitamin C and E
      (dementia: HR=0.93, 95% CI=0.72-1.20; AD: HR=1.00, 95% CI=0.73-1.35) and either
      outcome. CONCLUSION: In this study, the use of supplemental vitamin E and C,
      alone or in combination, did not reduce risk of AD or overall dementia over 5.5
      years of follow-up.

PMID- 18047493
TI  - Health care for older Americans with multiple chronic conditions: a research
      agenda.
AB  - In response to the substantial and increasing healthcare requirements of older
      adults with multiple chronic conditions and acknowledgment of major gaps in
      knowledge and funding, two expert meetings were convened to identify a research
      agenda addressing the needs of this population. Research priorities are to
      develop and evaluate more-effective models of health care, develop and evaluate
      management practices and organizational structures that lead to improved long
      term care, develop and implement relevant and effective preventive health
      strategies, determine the most effective interventions in patients who have
      concurrent cognitive or emotional impairments, and determine how interventions
      during and after hospitalization affect the outcomes of hospitalized patients.

PMID- 18047494
TI  - Outcome of septic shock in older adults after implementation of the sepsis
      "bundle".
AB  - OBJECTIVES: To evaluate the effect on 28-day mortality of implementation of a
      sepsis "bundle" protocol for the treatment of older adults with septic shock.
      DESIGN: Observational prospective study with a historical control group. SETTING:
      Tertiary care center. PARTICIPANTS: Eighty-seven consecutive patients recruited
      between May 2004 and February 2007 matched to a historic group identified between
      March 2001 and April 2004. INTERVENTIONS: Implementation of a sepsis protocol for
      the management of septic shock. RESULTS: Subjects who were treated according to
      the sepsis "bundle" had an absolute risk reduction in 28-day mortality of 16%
      (95% confidence interval (CI)=-31% to -2%). The treatment group received a larger
      volume of fluid in the first 6 hours of presentation (3,960 +/- 1,990 vs 2,490 +/
      1,020 mL; P<.001) and lower doses of vasopressors (maximum dosage of
      norepinephrine 0.51 microg/kg per min (range 0.12-1.7) vs 0.98 microg/kg per min
      (range 0.15-3.1) P=.009). A high prevalence of adrenal insufficiency (86%) was
      identified in the study population. There were no significant differences between
      the treatment and control groups in the surviving patients with respect to
      duration of mechanical ventilation (median 8.5 vs 12.0, respectively; P=.07) or
      intensive care unit length of stay (median 12 days vs 15 days; P=.08). According
      to Cox regression analysis, implementation of the sepsis bundle protocol was
      independently associated with better 28-day survival (hazard ratio=0.54, 95%
      CI=0.33-0.86; P=.01). CONCLUSION: Older patients with septic shock had a better
      28-day survival rate when treated with a comprehensive sepsis "bundle" protocol.

PMID- 18047495
TI  - Assuring quality end-of-life care: imperative to expand the evidence base in
      concert with growth of the field.

PMID- 18047496
TI  - Ethnic disparities in hospice use among Asian-American and Pacific Islander
      patients dying with cancer.
AB  - Asian Americans and Pacific Islanders (AAPIs) are a rapidly growing population in
      the United States, yet little is known about hospice use and length of stay in
      hospice of older AAPIs dying with cancer. A retrospective study was conducted of
      the last year of life of AAPI and white Medicare beneficiaries registered in the
      Surveillance, Epidemiology, and End Results Program. White (n=175,467) and AAPI
      (n=8,614) patients aged 65 and older who were dying with lung, colorectal,
      breast, prostate, gastric, or liver cancer were studied. Cox proportional hazards
      models were used to examine hospice use and length of stay in hospice. All AAPI
      subgroups studied had lower rates of hospice use (Chinese (adjusted hazard ratio
      (HR)=0.62, 95% confidence interval (CI)=0.55-0.69), Japanese (adjusted HR=0.67,
      95% CI=0.60-0.73), Filipino (adjusted HR=0.61, 95% CI=0.54-0.70),
      Hawaiian/Pacific Islanders (adjusted HR=0.78, 95% CI=0.67-0.91), and other Asians
      (adjusted HR=0.70), 95% CI=0.55-0.90) than white patients, adjusting for patient
      demographic and clinical characteristics. Of those who enrolled in hospice
      (approximately 20% of the total sample), Japanese Americans had a shorter median
      length of stay (21 days), and Filipino Americans had a longer median length of
      stay (32 days) than white patients (26 days). Overall, approximately 20% of
      patients enrolled within 7 days of death, and only 6% had hospice stays that were
      longer than 2 months, with no significant differences across racial or ethnic
      groups. In conclusion, in every ethnic subgroup studied, AAPIs were less likely
      than whites to enroll in hospice. Further research is needed to understand these
      differences and eliminate potential barriers to hospice care.

PMID- 18047497
TI  - Reflections on a 'virtual' practice development unit: changing practice through
      identity development.
AB  - AIMS: This paper draws together the personal thoughts and critical reflections of
      key people involved in the establishment of a 'virtual' practice development unit
      of clinical nurse specialists in the south of England. BACKGROUND: This practice
      development unit is 'virtual' in that it is not constrained by physical or
      specialty boundaries. It became the first group of Trust-wide clinical nurse
      specialists to be accredited in the UK as a practice development unit in 2004.
      DESIGN AND METHODS: The local university was asked to facilitate the
      accreditation process via 11 two-hour audio-recorded learning sessions. Critical
      reflections from practice development unit members, leaders and university staff
      were written 12 months after successful accreditation, and the framework of their
      content analysed. FINDINGS AND DISCUSSION: Practice development was seen as a way
      for the clinical nurse specialists to realize their potential for improving
      patient care by transforming care practice in a collaborative, interprofessional
      and evolutionary manner. The practice development unit provided a means for these
      nurses to analyse their role and function within the Trust. Roberts' identity
      development model for nursing serves as a useful theoretical underpinning for the
      reflections contained in this paper. CONCLUSIONS: These narratives provide
      another example of nurses making the effort to shape and contribute to patient
      care through organizational redesign. This group of nurses began to realize that
      the structure of the practice development unit process provided them with the
      means to analyse their role and function within the organization and, as they
      reflected on this structure, their behaviour began to change. RELEVANCE TO
      CLINICAL PRACTICE: Evidence from these reflections supports the view that
      practice development unit participants have secured a positive and professional
      identity and are, therefore, better able to improve the patient experience.

PMID- 18047498
TI  - Sleep-disordered breathing and cognition in older women.
AB  - OBJECTIVES: To investigate the association between objectively measured sleep
      disordered breathing (SDB) and cognitive impairment in community-dwelling older
      women and to determine whether the apolipoprotein E (APOE) epsilon4 allele
      modifies this association. DESIGN: Cross-sectional. SETTING: Participants' homes
      and two sites of the Study of Osteoporotic Fractures (SOF). PARTICIPANTS: Four
      hundred forty-eight women with a mean age+/-standard deviation (SD) of 82.8+/
      3.4. MEASUREMENTS: Participants completed the Mini-Mental State Examination
      (MMSE), Trail Making Test Part B (Trails B), and polysomnography (PSG). SDB
      indices were the apnea-hypopnea index (AHI), the central apnea index (CAI), and
      oxygen saturation (SaO2) nadir less than 80%. APOE epsilon4 was determined for a
      subset of 242 women. Cognitive impairment was defined as 1.5 SDs or more from the
      sample mean on either cognitive test (MMSE or Trails B). RESULTS: All SDB indices
      were associated with cognitive impairment according to the MMSE (AHI (per SD,
      odds ratio (OR)=1.4, 95% confidence interval (CI)=1.03-1.9), AHI of > or = 30
      (OR=3.4, 95% CI=1.4-8.1), SaO2 nadir < 80% (OR=2.7, 95% CI=1.1-6.6), and CAI (per
      SD, OR=1.4, 95% CI=1.1-1.7)). Weaker, nonsignificant associations emerged between
      SDB and Trails B. In women who completed genotyping, each SD increase in AHI was
      associated with 70% greater odds of cognitive impairment according to the MMSE
      (OR=1.7, 95% CI=1.2-2.6). Women with the epsilon4 allele had a nearly five times
      greater odds of impairment (per SD, OR=4.6, 95% CI-1.0-20.7); the association was
      smaller and nonsignificant in women without the epsilon4 allele (per SD, OR=1.5,
      95% CI-0.9-2.4; P for interaction=.08). CONCLUSION: SDB is an important risk
      factor for cognitive impairment in older women, especially those with the APOE
      epsilon4 allele. Mechanisms linking these disorders need to be identified.

PMID- 18047499
TI  - Randomized controlled trial of intravenous dexamethasone to prevent relapse in
      acute migraine headache.
AB  - OBJECTIVES: Migraine headache is a common presentation in the emergency
      department (ED). Inflammation is thought to play a role in the pathophysiology of
      migraine and there is conflicting evidence regarding the effect of
      corticosteroids on reducing early recurrences. We conducted a randomized clinical
      trial to test the hypothesis that dexamethasone (DEX) reduced headaches after
      discharge and examine the factors associated with relapse. METHODS: Consenting
      adults (18 and older) presenting with acute migraine at 4 EDs were enrolled. In
      addition to standard intravenous (IV) abortive therapy, using concealed
      allocation patients were randomized to receive IV DEX (15 mg) or placebo (PLA) in
      a double-blind fashion. Relapse was defined as a return to the ED, an urgent
      clinic visit, or a headache that precluded normal activity reported during follow
      up telephone interviews 48-72 hours and 7 days after ED discharge. Intention to
      treat was used for all final analyses. RESULTS: A total of 130 patients were
      randomized; 126 patients are included in the analysis (one patient left prior to
      treatment and 3 enrolled twice); 64 received DEX and 62 received PLA. Mean age
      was 35 years, 81% was female; most (77%) suffered from headaches at least
      monthly. On a 10-point visual analog scale (VAS), the median pain scores were 8
      at presentation, and 2 at discharge. At 48-72 hours, relapses occurred in 14/64
      (22%) in the DEX group and 20/62 (32%) in the PLA groups (OR = 0.6; 95% CI: 0.3
      1.3). By day 7, 18/64 (28%) in the DEX group had relapsed, compared with 25/62
      (40%) in the PLA group (OR = 0.6; 95% CI: 0.3-1.3). Controlling for treatment
      assignment, relapse was more common when headache pain was incompletely relieved
      (VAS > 2) at ED discharge (OR = 2.2; 95% CI: 1.1-5.4). CONCLUSIONS: The overall
      relapse rate differed from those previously reported; however, DEX failed to
      reduce headache relapses after ED discharge. Relapse was closely associated with
      incomplete pain relief at discharge. Further research is needed to determine the
      factors associated with migraine relapse.

PMID- 18047500
TI  - Elimination of migraine-associated nausea in patients treated with rizatriptan
      orally disintegrating tablet (ODT): a randomized, double-blind, placebo
      controlled study.
AB  - OBJECTIVE: To confirm the efficacy of rizatriptan 10 mg orally disintegrating
      tablet (ODT) for the elimination of migraine-associated nausea. BACKGROUND:
      Pooled studies of rizatriptan analyzing elimination of nausea as a secondary
      endpoint showed that 65% of rizatriptan patients reported elimination of nausea
      at 2 hours compared with 41% of patients taking placebo. METHODS: This was a
      multicenter, randomized, double-blind, placebo-controlled single-attack trial
      enrolling adult patients with at least a 6-month history of migraine who
      typically experience migraine-associated nausea. Patients treated a moderate or
      severe migraine headache at the earliest sign of nausea with either rizatriptan
      10 mg ODT or placebo (2 : 1). The primary endpoint was elimination of nausea at 2
      hours postdose, and the secondary endpoint was pain relief at 2 hours postdose.
      RESULTS: Although not statistically significant, a greater percentage of patients
      had elimination of nausea at 2 hours with rizatriptan compared with placebo
      (70.3% vs 62.0%, P = .165, odds ratio [95% CI] = 1.45 [0.86, 2.46]). When
      patients were grouped by baseline headache severity, rizatriptan showed a greater
      advantage than placebo for patients with moderate pain (rizatriptan 72.8% vs
      placebo 57.4%), but no difference for patients with severe pain (rizatriptan
      67.7% vs placebo 66.7%). There were significantly more patients who achieved 2
      hour pain relief with rizatriptan (69.7% vs 54.3%, P = .012, odds ratio [95% CI]
      = 1.94 [1.16, 3.25]). CONCLUSION: Although the efficacy of rizatriptan 10 mg ODT
      for the elimination of migraine-associated nausea was comparable to that seen in
      previous rizatriptan trials, the higher-than-usual placebo response prevented a
      finding of a statistically significant difference. There was a sizable difference
      in placebo response between patients who treated moderate vs severe migraine.
      Rizatriptan was effective for 2-hour pain relief.

PMID- 18047501
TI  - Botulinum toxin type A as migraine preventive treatment in patients previously
      failing oral prophylactic treatment due to compliance issues.
AB  - OBJECTIVE: To examine the efficacy and safety of and satisfaction with botulinum
      toxin type A (BoNTA; BOTOX: Allergan, Inc., Irvine, CA) for prophylactic
      treatment of migraine headache in patients previously failing prophylaxis because
      of issues pertaining to compliance. Background.- Numerous factors (eg, adverse
      effects, tolerability, cost, frequency of dosage, hesitancy to take daily
      medication, failure to complete treatment) negatively influence compliance with
      the preventive pharmacology for migraine prophylaxis. BoNTA may offer benefit in
      improving compliance because of its long duration of action, injectable route of
      administration, and its tolerability (adverse event [AE]) profile. METHODS: This
      was a randomized, double-blind, single-center, placebo-controlled study (months 1
      to 3) of BoNTA with a cross-over to open-label BoNTA treatment (months 4 to 6).
      Criteria for enrollment included patients with disabling headache (International
      Headache Society, International Classification of Headache Disorders [ICHD-I]
      diagnosis 1.1, 1.2, 1.7, or 2.2, and Headache Impact Test [HIT]-6 scores >/=56)
      previously failing prophylaxis because of compliance, tolerability, or adherence
      issues. After baseline evaluation, subjects were randomized 2 : 1 to a single set
      of BoNTA (139 units [U] total; 17 sites/6 muscle groups) or placebo injections.
      After month 3, only placebo-treated subjects were eligible to receive BoNTA in
      the open-label continuation study. Treatment outcomes were evaluated by headache
      episodes and days and maximum headache severity. Headache impact was assessed by
      the HIT-6, Migraine Disability Assessment (MIDAS) score, and Quality of Life
      (QoL) questionnaires. Treatment satisfaction was assessed with the Migraine
      Impact Questionnaire (MIQ), which included MIDAS and QoL. RESULTS: Of the 73
      subjects screened, 61 (40 BoNTA; 21 placebo) with migraine headache diagnosis 1.1
      and 1.2 who met all study criteria were enrolled in the 3-month, blinded study,
      with 54 completing the study; 19 of 21 placebo-treated subjects participated in
      the open-label period (months 4 to 6), with 18 completing the study. Between
      group comparisons, demonstrated through analysis of the subjects' headache
      diaries, did not reach statistical significance at months 1 to 3 for the number
      of headache episodes or days (primary endpoint). At month 2, a decrease from
      baseline in the number of headache episodes (-0.99 +/- 2.38; P = .0147 vs 0.42 +/
      3.23; P = not significant [NS]) and headache days (-1.52 +/- 3.84; P = .0194 vs
      0.23 +/- 4.67; P = NS) was noted in the BoNTA-treated subjects but not in the
      placebo-treated subjects, respectively. During the open-label study, BoNTA
      treated subjects had a decrease in the number of headache episodes at months 5
      and 6 (-1.58 +/- 2.88 and -1.58 +/- 2.85, respectively; P < .05 vs baseline for
      both) and headache days at months 5 and 6 (-2.84 +/- 4.47 and -2.73 +/- 4.86,
      respectively; P < .05 vs baseline for both). BoNTA did not affect maximum
      headache severity compared with baseline or placebo during the first 3 months of
      the study. A decrease in HIT-6 scores was significantly greater for BoNTA-treated
      subjects than for placebo-treated subjects at month 3 (-7.77 vs -3.58, P =
      .0466). Within-group decreases in HIT-6 scores were significant in BoNTA-treated
      subjects during each month of the blinded trial (-5.10 +/- 8.85, -6.63 +/- 7.49, 
      7.77 +/- 8.78 for months 1 to 3, respectively; P < .0001 for all vs baseline) and
      throughout the open-label portion of the study (-7.89 +/- 6.48, -10.39 +/- 10.81,
      -9.00 +/- 11.12 for months 4 to 6, respectively; P < .01 for all vs baseline).
      The within-group decrease in placebo-treated subjects was significant at months 1
      and 3 (-3.35 +/- 6.07 and -3.58 +/- 5.40, respectively; P < .05 for both). At 3
      months, BoNTA was significantly better than placebo (P = .001) in the reduction
      of MIDAS total score. The change from baseline in the MIDAS total scores was
      significant in BoNTA-treated subjects (-21.62 +/- 38.70; P < .0001) but not in
      placebo recipients (4.76 +/- 18.85; P = NS). BoNTA-treated subjects showed
      improvement in 11 of 13 and 7 of 13 assessments of treatment satisfaction in MIQ
      at months 3 and 6, respectively, while the placebo group showed no improvement at
      any measured time interval in the study. At month 3 (blinded period), there were
      no treatment-related AEs reported in both groups. However, there were 18
      possible/probable occurrences of treatment-related AEs in the BoNTA group. At
      month 6 (open-label period), 4 treatment-related AEs were reported, along with 2
      possible occurrences. The majority of treatment-related AEs were transient and
      mild to moderate in severity, with no subjects discontinuing the study because of
      AEs. CONCLUSIONS: BoNTA-treated subjects showed improvements from baseline in
      measures of headache frequency, and improvements from baseline and in comparison
      with placebo treatment in headache impact and treatment satisfaction at multiple
      time points in this study. However, BoNTA-treated subjects did not differ from
      placebo-treated subjects in measures of headache frequency and severity. BoNTA
      may be a useful treatment option for headache patients demonstrating poor
      compliance, adherence, or AE profile with oral prophylactic regimens.

PMID- 18047502
TI  - Botulinum toxin type A and divalproex sodium for prophylactic treatment of
      episodic or chronic migraine.
AB  - OBJECTIVE: To compare the efficacy and safety of botulinum toxin type A (BoNTA;
      BOTOX: Allergan, Inc.) and divalproex sodium (DVPX; DEPAKOTE: Abbott
      Laboratories) as prophylaxis in reducing disability and impact associated with
      migraine. BACKGROUND: There is a need for effective, well-tolerated prophylactic
      treatment of migraine. DESIGN/METHODS: This was a randomized, double-blind,
      single-center prospective study. Fifty-nine patients received either BoNTA 100
      U/placebo-DVPX bid or placebo-BoNTA/DVPX 250 mg bid. BoNTA/placebo injections
      were given at Day 0 and at Month 3. Patients were evaluated at Months 1, 3, 6,
      and 9. RESULTS: Both treatments showed significant improvements in migraine
      disability scores and reductions in headache days and headache index. A trend to
      decreased headache severity was observed with BoNTA. A greater percentage of DVPX
      patients reported adverse events possibly related to treatment (DVPX 75.8% vs
      BoNTA 50%, P = .04) and discontinued because of adverse events (DVPX 27.6% vs
      BoNTA 3.3%, P = .012). CONCLUSIONS: Both BoNTA and DVPX significantly reduced
      disability associated with migraine; BoNTA had a favorable tolerability profile
      compared with DVPX.

PMID- 18047503
TI  - Pemphigoid nodularis associated with psoriatic erythroderma: successful treatment
      with suplatast tosilate.

PMID- 18047504
TI  - Long-term efficacy of a single course of infliximab in hidradenitis suppurativa.
AB  - BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory skin disease
      characterized by abscess formation, predominantly in the axillae and groins. The
      disease is difficult to treat and has a severe impact on quality of life.
      Recently, several case reports have been published describing successful
      treatment of hidradenitis suppurativa with infliximab and other tumour necrosis
      factor alpha inhibitors. OBJECTIVES: To evaluate the long-term efficacy of a
      single course of infliximab. METHODS: Ten patients with severe, recalcitrant
      hidradenitis were treated with infliximab (three infusions of 5 mg kg(-1) at
      weeks 0, 2 and 6) and followed up for at least 1 year. The disease activity was
      measured using laboratory parameters and a recently developed acne score. The
      patients rated the efficacy of infliximab on a 10-point scale at regular
      intervals. Quality of life was measured before and after treatment using the
      Dermatology Quality of Life Index (DQLI). RESULTS: All patients improved within 2
      6 weeks. The average acne score diminished from 164+/-50 (mean+/-SD) before
      treatment to 89+/-49 after 1 year (P=0.002). The mean CRP (C-reactive protein)
      was reduced from 31.7 mg mL(-1) to 5.5 mg mL(-1) after 1 month (P=0.015).
      Patients judged the efficacy with a score of 7.9. The mean DQLI was reduced from
      18.4+/-7.9 before treatment to 9.3+/-9.1 after 1 year (P=0.007). In three
      patients long-lasting improvement was observed, with no recurrence of lesions in
      a 2-year follow-up period. The other patients showed recurrence of lesions after
      8.5 months (range 4.3-13.4 months). CONCLUSIONS: Infliximab is an effective
      treatment in severe hidradenitis suppurativa, leading to reduction of symptoms
      for a prolonged period.

PMID- 18047505
TI  - Lichenoid drug eruption to terazosin.

PMID- 18047506
TI  - A case of bromoderma and bromism.

PMID- 18047507
TI  - Photosensitizing activity of hypericin and hypericin acetate after topical
      application on normal mouse skin.
AB  - BACKGROUND: Hypericin, originating from Hypericum perforatum, is a potent
      photosensitizer known to induce skin phototoxicity when given systemically.
      Previously, we have examined the penetration and distribution of hypericin and
      its acetate ester in the skin of hairless mice after topical application.
      OBJECTIVES: In this study, we assessed the time course and skin histopathology of
      the phototoxic response after a single topical application of hypericin and
      hypericin acetate, and subsequent irradiation. The amount of blood-borne
      photosensitizer and the skin clearance, as well the remaining photosensitizing
      capacity as a function of time, were evaluated. Furthermore, elicited phototoxic
      responses were compared with those after application of methyl aminolaevulinic
      acid (Me-ALA). METHODS: At different time points after topical application of
      hypericin (0.1-1%) and hypericin acetate (0.015-1.5%) onto mouse ears,
      penetration and retention of hypericin were assessed by fluorescence microscopy.
      After definite application times, the ears were irradiated (10 J cm(-2), 20 mW
      cm(-2)). Ear thickness measurements were conducted daily, and frequently ear
      samples were taken for histological analysis. RESULTS: Application of hypericin
      on mouse ears resulted only in limited phototoxicity, probably due to confined
      penetration into the epidermal layers. Extended penetration achieved by
      administration of hypericin acetate did give rise to a more severe and prolonged
      response after irradiation, characterized by intense erythema and ear swelling.
      Skin damage induced by 0.15% hypericin acetate application completely healed in
      14 days without scar formation. After a single application of hypericin acetate,
      the residual photosensitizing capacity was found to decline quickly and was
      hardly detectable after 7 days. Under the experimental conditions used, hypericin
      acetate induced equal or more severe phototoxic responses compared with Me-ALA,
      depending on the concentration. CONCLUSIONS: Our results indicate that hypericin
      is an effective photosensitizer not only after systemic administration, but also
      after topical application, especially when applied as its precursor acetate
      ester. Moreover, our data provide some insights on safety limits and the time
      course of skin phototoxicity following hypericin and hypericin acetate
      application. These data will aid in developing protocols for future photodynamic
      therapy in the dermatological clinic.

PMID- 18047508
TI  - Confirmed cancer trends in families of patients with multiple cancers including
      cutaneous melanoma.

PMID- 18047509
TI  - Cost-effectiveness of wart treatment.

PMID- 18047511
TI  - Use of a spectrophotometric intracutaneous analysis device in the real-time
      diagnosis of melanoma.

PMID- 18047512
TI  - Sickle cell leg ulcers: a frequently disabling complication and a marker of
      severity.
AB  - BACKGROUND: Leg ulcers are a poorly known and underestimated complication of
      sickle cell disease (SCD), but in our experience they often appear as a severely
      disabling condition, associated with the most severe forms of the disease.
      OBJECTIVES: To assess the characteristics, complications, repercussion on quality
      of life and associations of SCD ulcers. METHODS: Case series of 20 patients
      followed in a French referral centre for SCD and who had previous/present leg
      ulcers. RESULTS: Median ulcerated area was 12 cm2 and median time spent with
      ulcers was 29.5 months. Locoregional infections developed in 85%, ankle stiffness
      in 50% and mood disorders in 85%. Ninety per cent of patients needed analgesics,
      20% being opioids. Median loss of time from work was 12.5 months. The Short Form
      36 Health Survey showed physical and mental component summary scores of 41.5 and
      40.7, respectively, indicating severe alteration close to that found in lung
      cancer or haemodialysis. Two categories of SCD leg ulcers were distinguished,
      defined by a 1-year duration cut off. The 'prolonged' ulcers had larger surfaces,
      tended to recur more frequently and led to more infection and depression. Several
      SCD complications were associated with leg ulcers, notably priapism, pulmonary
      hypertension, stroke and acute chest syndrome. CONCLUSIONS: Leg ulcers are a
      major complication of SCD, given their severe consequences and frequent
      association with other specific organ damage, and they constitute in their
      'prolonged' form a severely disabling condition that remains an important
      therapeutic challenge.

PMID- 18047513
TI  - Post-kala-azar dermal leishmaniasis and borderline tuberculoid leprosy.

PMID- 18047514
TI  - Dermoid cyst with magnetic resonance image of sack-of-marbles.

PMID- 18047516
TI  - Genetics of melanoma tumorigenesis.
AB  - Melanoma therapy is moving away from combinatorial approaches and towards newer
      targeted strategies. With the identification of mutations in various RAS pathway
      genes, there are now tremendous opportunities to bring inhibitors of RAS
      signalling to the clinical arena.

PMID- 18047517
TI  - Comparison of the depth profiles of water and water-binding substances in the
      stratum corneum determined in vivo by Raman spectroscopy between the cheek and
      volar forearm skin: effects of age, seasonal changes and artificial forced
      hydration.
AB  - BACKGROUND: Dermatologists and cosmetic scientists are becoming increasingly
      interested in stratum corneum (SC) hydration because the SC plays an important
      role in keeping the skin surface soft and smooth. However, conventional in vivo
      noninvasive methods do not provide direct information about the depth profiles of
      water content or SC components that hold water. OBJECTIVES: To study the depth
      profiles of water and SC components in vivo by Raman spectroscopy, and to analyse
      the changes due to age, anatomical location, season and water application.
      METHODS: In vivo Raman spectra of the skin of the cheek and the volar forearm
      were obtained from 50 healthy Japanese volunteers of different ages (age range 22
      76 years) with a confocal Raman spectrometer. The depth-dependent profiles of
      water and of SC water-binding components were calculated from the respective
      Raman spectra. RESULTS: The depth profile of the SC water content was observed in
      a pattern ranging from around 30% (water/wet tissue) at the outermost layer of
      the SC to about 70% at the deeper living layer. Although the water content at a
      depth of 10-30 microm in the forearm skin tended to be lower in older subjects
      than in younger subjects, no such difference was found in the much thinner SC of
      the cheek. Moreover, there was no seasonal difference in depth profile of water
      content from the mid part of the SC to an 80-microm depth from the skin surface
      both in the cheek and in the forearm. The water content of all the evaluated SC
      components showed a gradual decrease from the surface to deeper portions. The
      mean amounts of lactate in the forearm skin and cholesterol in the cheek skin
      were significantly higher in younger subjects than in older subjects. In
      contrast, the levels of free amino acids and trans-urocanic acid were higher in
      the forearm skin of older subjects than in younger subjects. The relative amounts
      of urea and lactate were the highest in summer, when that of trans-urocanic acid
      was the lowest. Prolonged water application on the forearm skin even for 90 min
      resulted in a remarkable increase in water content throughout the SC, even
      reaching the granular layer, which was only gradually released from the upper
      part of the SC after discontinuation of the hydration procedure. CONCLUSIONS: Our
      present findings suggest that changes in the concentration depth profiles of
      water, free amino acids and lipids in the skin depend on age, anatomical site and
      season. These findings indicate the important roles played by various water
      holding substances in the SC in the regulation of SC water content.

PMID- 18047518
TI  - A randomized, single-blind comparison of topical clindamycin + benzoyl peroxide
      and adapalene in the treatment of mild to moderate facial acne vulgaris.
AB  - BACKGROUND: Antibiotics are often combined with other agents to provide topical
      acne treatments that are effective against both inflammatory and noninflammatory
      lesions and minimize the development of antibiotic resistance. Retinoids and
      associated treatments also have anti-inflammatory activity and decrease
      microcomedo formation. To date, few direct comparisons of these different acne
      treatments have been conducted. OBJECTIVES: To compare the clinical effectiveness
      of two treatments for facial acne: a ready-mixed once-daily gel containing
      clindamycin phosphate 10 mg mL(-1) + benzoyl peroxide 50 mg mL(-1) (CDP + BPO;
      Duac; Stiefel, High Wycombe, U.K.) and a once-daily gel containing adapalene 0.1%
      (ADA; Differin; Galderma, Watford, U.K.). METHODS: In this assessor-blind,
      randomized study; 65 patients were treated with CDP + BPO once daily and 65
      patients with ADA once daily. The treatment period was 12 weeks and lesion
      counts, acne grade and global improvement were assessed at weeks 1, 2, 4, 8 and
      12. RESULTS: CDP + BPO showed an earlier onset of action with a faster
      significant reduction in inflammatory and total lesion counts than ADA. A between
      group comparison of the percentage change from baseline showed that CDP + BPO was
      statistically significantly superior to ADA from week 1 onwards both for
      inflammatory lesions (P < or = 0.001) and for total lesions (P < or = 0.004).
      While 76% of inflammatory lesions remained at week 2 for patients using ADA, in
      contrast, only 55% of inflammatory lesions remained at week 2 in the CDP + BPO
      group, resulting in a treatment effect of 1.38. Thus CDP + BPO removed 38% more
      inflammatory lesions than ADA at this timepoint. The trend in favour of CDP +
      BPO, although less marked, continued to the end of the study. CDP + BPO was
      better tolerated than ADA, with a greater proportion of ADA-treated patients
      experiencing treatment-related adverse events. Adjunctive topical or oral agents
      and their impact on acne were not studied in this trial. Due to product
      differences, this study could not be double blinded but was only single
      (assessor) blinded. CONCLUSIONS: CDP + BPO and ADA are both effective treatments
      for acne, but CDP + BPO has a significantly earlier onset of action, is
      significantly more effective against inflamed and total lesions and is better
      tolerated, which should improve patient compliance.

PMID- 18047519
TI  - Explaining phenotype heterogeneity in patients with psoriasis.
AB  - Psoriasis is a heterogeneous disorder with many different phenotypes. Further,
      different forms may alter their morphology and course of disease in that, for
      instance, plaque-type psoriasis may become pustular and vice versa. With
      advancing insight in immunopathology phenotype switching can now be explained by
      directional changes from T cell-mediated pathology to an inflammatory
      neutrophilic pattern which is driven by innate signalling. Within this framework
      not a single 'antigen' but various causative agents play a key role.

PMID- 18047520
TI  - Human papillomavirus-associated increase in p16INK4A expression in penile lichen
      sclerosus and squamous cell carcinoma.
AB  - BACKGROUND: Human papillomaviruses (HPVs) are sexually transmitted human
      carcinogens that may play a role in the oncogenesis of penile cancer. OBJECTIVES:
      To investigate the role of HPV infection and expression of the tumour suppressor
      protein p16INK4A in the pathogenesis of penile cancer. METHODS: By means of
      polymerase chain reaction amplification and reverse hybridization line probe
      assay to detect HPV infection, and immunohistochemical staining for p16INK4A and
      Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent
      penile lichen sclerosus (LS) lesions from 46 patients. RESULTS: HPV DNA was found
      in 54% of penile SCCs and 33% of penile LS cases in single and multiple
      infections. High-risk HPV 16 was the predominant HPV type detected. No
      relationship between Ki67 expression and HPV infection was observed. Strong
      immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS
      and penile SCC. In our penile SCC series the cancer margins were also associated
      with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC
      cases associated with LS and in six of the 11 SCC lesions not involving LS.
      CONCLUSIONS: Our study shows a high prevalence of HPV 16 and p16INK4A expression
      in penile lesions, consistent with an active role for HPV in interfering with the
      retinoblastoma pathway. High-risk HPV infection could be involved in the
      tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV
      vaccines has the potential to prevent these cancers.

PMID- 18047521
TI  - Impact of adalimumab treatment on health-related quality of life and other
      patient-reported outcomes: results from a 16-week randomized controlled trial in
      patients with moderate to severe plaque psoriasis.
AB  - BACKGROUND: Health-related quality of life (HRQOL) and other patient-reported
      outcomes (PROs) are important in evaluating the impact of psoriasis and its
      treatment. OBJECTIVES: To assess the impact of adalimumab treatment on HRQOL and
      other PROs in patients with moderate to severe psoriasis. METHODS: A 16-week,
      double-blind, double-dummy, randomized controlled trial evaluated the efficacy
      and safety of adalimumab in 271 adults with moderate to severe chronic plaque
      psoriasis. Patients were randomized in a 2:2:1 ratio to adalimumab, methotrexate
      (MTX) or placebo. PROs were evaluated throughout the study and included the
      Dermatology Life Quality Index (DLQI), Patient's Global Assessment of disease
      severity, plaque psoriasis and psoriatic arthritis pain visual analogue scale
      (VAS), Psoriasis-Related Pruritus Assessment and EuroQOL 5D (EQ-5D). RESULTS:
      Statistically significant differences were observed between the adalimumab- and
      placebo-treated and the MTX-treated groups on mean DLQI total scores during the
      16-week double-blind study (both P<0.001). Significant differences, favouring
      adalimumab compared with placebo, were also observed on the Patient's Global
      Assessment of disease severity (P<0.001), VAS for pain (P<0.001), Psoriasis
      Related Pruritus Assessment (P<0.001), EQ-5D VAS (P<0.001) and EQ-5D index score
      (P<0.01). Compared with MTX, adalimumab resulted in statistically significantly
      greater improvements in the Patient's Global Assessment of disease severity
      (P<0.001), the VAS for pain (P<0.01) and the Psoriasis-Related Pruritus
      Assessment (P<0.001). CONCLUSIONS: Adalimumab was efficacious in improving
      dermatology-specific HRQOL, disease control and symptom outcomes in patients with
      moderate to severe psoriasis.

PMID- 18047522
TI  - Use of a spectrophotometric intracutaneous analysis device in the real-time
      diagnosis of melanoma.

PMID- 18047523
TI  - Efficacy and safety results from the randomized controlled comparative study of
      adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION).
AB  - BACKGROUND: Biologic therapies such as adalimumab, a tumour necrosis factor
      antagonist, are safe and effective in the treatment of moderate to severe chronic
      plaque psoriasis. OBJECTIVES: To compare a biologic agent with methotrexate, a
      traditional systemic agent, to define clearly the role of biologics in psoriasis.
      METHODS: Patients with moderate to severe plaque psoriasis were randomized to
      adalimumab (80 mg subcutaneously at week 0, then 40 mg every other week, n=108),
      methotrexate (7.5 mg orally, increased as needed and as tolerated to 25 mg
      weekly; n=110) or placebo (n=53) for 16 weeks. The primary efficacy endpoint was
      the proportion of patients achieving at least a 75% improvement in the Psoriasis
      Area and Severity Index (PASI 75) after 16 weeks. Safety was assessed at all
      visits through week 16. RESULTS: After 16 weeks, 79.6% of adalimumab-treated
      patients achieved PASI 75, compared with 35.5% for methotrexate (P<0.001 vs.
      adalimumab) and 18.9% for placebo (P<0.001 vs. adalimumab). Statistically
      significantly more adalimumab-treated patients (16.7%) than methotrexate-treated
      patients (7.3%) or placebo-treated patients (1.9%) achieved complete clearance of
      disease. The response to adalimumab was rapid, with a 57% improvement in mean
      PASI observed at week 4. Adverse events were similar across treatment groups.
      Adverse events leading to study discontinuation were greatest in the methotrexate
      group, primarily because of hepatic-related adverse events. CONCLUSIONS: After 16
      weeks, adalimumab demonstrated significantly superior efficacy and more rapid
      improvements in psoriasis compared with either methotrexate or placebo.

PMID- 18047524
TI  - Conditional generalized estimating equations for the analysis of clustered and
      longitudinal data.
AB  - A common and important problem in clustered sampling designs is that the effect
      of within-cluster exposures (i.e., exposures that vary within clusters) on
      outcome may be confounded by both measured and unmeasured cluster-level factors
      (i.e., measurements that do not vary within clusters). When some of these are
      ill/not accounted for, estimation of this effect through population-averaged
      models or random-effects models may introduce bias. We accommodate this by
      developing a general theory for the analysis of clustered data, which enables
      consistent and asymptotically normal estimation of the effects of within-cluster
      exposures in the presence of cluster-level confounders. Semiparametric efficient
      estimators are obtained by solving so-called conditional generalized estimating
      equations. We compare this approach with a popular proposal by Neuhaus and
      Kalbfleisch (1998, Biometrics 54, 638-645) who separate the exposure effect into
      a within- and a between-cluster component within a random intercept model. We
      find that the latter approach yields consistent and efficient estimators when the
      model is linear, but is less flexible in terms of model specification. Under
      nonlinear models, this approach may yield inconsistent and inefficient
      estimators, though with little bias in most practical settings.

PMID- 18047525
TI  - A general framework for the analysis of animal resource selection from telemetry
      data.
AB  - We propose a general framework for the analysis of animal telemetry data through
      the use of weighted distributions. It is shown that several interpretations of
      resource selection functions arise when constructed from the ratio of a use and
      availability distribution. Through the proposed general framework, several
      popular resource selection models are shown to be special cases of the general
      model by making assumptions about animal movement and behavior. The weighted
      distribution framework is shown to be easily extended to readily account for
      telemetry data that are highly autocorrelated; as is typical with use of new
      technology such as global positioning systems animal relocations. An analysis of
      simulated data using several models constructed within the proposed framework is
      also presented to illustrate the possible gains from the flexible modeling
      framework. The proposed model is applied to a brown bear data set from southeast
      Alaska.

PMID- 18047526
TI  - Estimating a predator-prey dynamical model with the parameter cascades method.
AB  - Ordinary differential equations (ODEs) are widely used in ecology to describe the
      dynamical behavior of systems of interacting populations. However, systems of
      ODEs rarely provide quantitative solutions that are close to real field
      observations or experimental data because natural systems are subject to
      environmental and demographic noise and ecologists are often uncertain about the
      correct parameterization. In this article we introduce "parameter cascades" as an
      improved method to estimate ODE parameters such that the corresponding ODE
      solutions fit the real data well. This method is based on the modified penalized
      smoothing with the penalty defined by ODEs and a generalization of profiled
      estimation, which leads to fast estimation and good precision for ODE parameters
      from noisy data. This method is applied to a set of ODEs originally developed to
      describe an experimental predator-prey system that undergoes oscillatory
      dynamics. The new parameterization considerably improves the fit of the ODE model
      to the experimental data sets. At the same time, our method reveals that
      important structural assumptions that underlie the original ODE model are
      essentially correct. The mathematical formulations of the two nonlinear
      interaction terms (functional responses) that link the ODEs in the predator-prey
      model are validated by estimating the functional responses nonparametrically from
      the real data. We suggest two major applications of "parameter cascades" to
      ecological modeling: It can be used to estimate parameters when original data are
      noisy, missing, or when no reliable priori estimates are available; it can help
      to validate the structural soundness of the mathematical modeling approach.

PMID- 18047527
TI  - Maximum likelihood ratio tests for comparing the discriminatory ability of
      biomarkers subject to limit of detection.
AB  - In this article, we consider comparing the areas under correlated receiver
      operating characteristic (ROC) curves of diagnostic biomarkers whose measurements
      are subject to a limit of detection (LOD), a source of measurement error from
      instruments' sensitivity in epidemiological studies. We propose and examine the
      likelihood ratio tests with operating characteristics that are easily obtained by
      classical maximum likelihood methodology.

PMID- 18047528
TI  - Clustered mixed nonhomogeneous Poisson process spline models for the analysis of
      recurrent event panel data.
AB  - A flexible semiparametric model for analyzing longitudinal panel count data
      arising from mixtures is presented. Panel count data refers here to count data on
      recurrent events collected as the number of events that have occurred within
      specific follow-up periods. The model assumes that the counts for each subject
      are generated by mixtures of nonhomogeneous Poisson processes with smooth
      intensity functions modeled with penalized splines. Time-dependent covariate
      effects are also incorporated into the process intensity using splines. Discrete
      mixtures of these nonhomogeneous Poisson process spline models extract functional
      information from underlying clusters representing hidden subpopulations. The
      motivating application is an experiment to test the effectiveness of pheromones
      in disrupting the mating pattern of the cherry bark tortrix moth. Mature moths
      arise from hidden, but distinct, subpopulations and monitoring the subpopulation
      responses was of interest. Within-cluster random effects are used to account for
      correlation structures and heterogeneity common to this type of data. An
      estimating equation approach to inference requiring only low moment assumptions
      is developed and the finite sample properties of the proposed estimating
      functions are investigated empirically by simulation.

PMID- 18047529
TI  - Efficient statistical inference procedures for partially nonlinear models and
      their applications.
AB  - Motivated by an analysis of a real data set in ecology, we consider a class of
      partially nonlinear models where both a nonparametric component and a parametric
      component are present. We develop two new estimation procedures to estimate the
      parameters in the parametric component. Consistency and asymptotic normality of
      the resulting estimators are established. We further propose an estimation
      procedure and a generalized F-test procedure for the nonparametric component in
      the partially nonlinear models. Asymptotic properties of the newly proposed
      estimation procedure and the test statistic are derived. Finite sample
      performance of the proposed inference procedures are assessed by Monte Carlo
      simulation studies. An application in ecology is used to illustrate the proposed
      methods.

PMID- 18047530
TI  - A new exact and more powerful unconditional test of no treatment effect from
      binary matched pairs.
AB  - We consider the problem of testing for a difference in the probability of success
      from matched binary pairs. Starting with three standard inexact tests, the
      nuisance parameter is first estimated and then the residual dependence is
      eliminated by maximization, producing what I call an E+M P-value. The E+M P-value
      based on McNemar's statistic is shown numerically to dominate previous
      suggestions, including partially maximized P-values as described in Berger and
      Sidik (2003, Statistical Methods in Medical Research 12, 91-108). The latter
      method, however, may have computational advantages for large samples.

PMID- 18047531
TI  - A test for constant fatality rate of an emerging epidemic: with applications to
      severe acute respiratory syndrome in Hong Kong and Beijing.
AB  - The etiology, pathogenesis, and prognosis for a newly emerging disease are
      generally unknown to clinicians. Effective interventions and treatments at the
      earliest possible times are warranted to suppress the fatality of the disease to
      a minimum, and inappropriate treatments should be abolished. In this situation,
      the ability to extract most information out of the data available is critical so
      that important decisions can be made. Ineffectiveness of the treatment can be
      reflected by a constant fatality over time while effective treatment normally
      leads to a decreasing fatality rate. A statistical test for constant fatality
      over time is proposed in this article. The proposed statistic is shown to
      converge to a Brownian motion asymptotically under the null hypothesis. With the
      special features of the Brownian motion, we are able to analyze the first passage
      time distribution based on a sequential tests approach. This allows the null
      hypothesis of constant fatality rate to be rejected at the earliest possible time
      when adequate statistical evidence accumulates. Simulation studies show that the
      performance of the proposed test is good and it is extremely sensitive in picking
      up decreasing fatality rate. The proposed test is applied to the severe acute
      respiratory syndrome data in Hong Kong and Beijing.

PMID- 18047532
TI  - Modeling nonhomogeneous Markov processes via time transformation.
AB  - Longitudinal studies are a powerful tool for characterizing the course of chronic
      disease. These studies are usually carried out with subjects observed at periodic
      visits giving rise to panel data. Under this observation scheme the exact times
      of disease state transitions and sequence of disease states visited are unknown
      and Markov process models are often used to describe disease progression. Most
      applications of Markov process models rely on the assumption of time homogeneity,
      that is, that the transition rates are constant over time. This assumption is not
      satisfied when transition rates depend on time from the process origin. However,
      limited statistical tools are available for dealing with nonhomogeneity. We
      propose models in which the time scale of a nonhomogeneous Markov process is
      transformed to an operational time scale on which the process is homogeneous. We
      develop a method for jointly estimating the time transformation and the
      transition intensity matrix for the time transformed homogeneous process. We
      assess maximum likelihood estimation using the Fisher scoring algorithm via
      simulation studies and compare performance of our method to homogeneous and
      piecewise homogeneous models. We apply our methodology to a study of delirium
      progression in a cohort of stem cell transplantation recipients and show that our
      method identifies temporal trends in delirium incidence and recovery.

PMID- 18047533
TI  - Modeling time series of animal behavior by means of a latent-state model with
      feedback.
AB  - We describe a family of models developed for time series of animal feeding
      behavior. The models incorporate both an unobserved state, which can be
      interpreted as the motivational state of the animal, and a mechanism for feedback
      to this state from the observed behavior. We discuss methods for evaluating and
      maximizing the likelihood of an observed series of behaviors, and thereby
      estimating parameters, and for inferring the most likely sequence of underlying
      states. We indicate several extensions of the models, including the incorporation
      of random effects. We apply these methods in an analysis of the feeding behavior
      of the caterpillar Helicoverpa armigera, and thereby demonstrate the potential of
      this family of models as a tool in the investigation of behavior.

PMID- 18047534
TI  - On the Bayesian estimation of a closed population size in the presence of
      heterogeneity and model uncertainty.
AB  - We consider the estimation of the size of a closed population, often of interest
      for wild animal populations, using a capture-recapture study. The estimate of the
      total population size can be very sensitive to the choice of model used to fit to
      the data. We consider a Bayesian approach, in which we consider all eight
      plausible models initially described by Otis et al. (1978, Wildlife Monographs
      62, 1-135) within a single framework, including models containing an individual
      heterogeneity component. We show how we are able to obtain a model-averaged
      estimate of the total population, incorporating both parameter and model
      uncertainty. To illustrate the methodology we initially perform a simulation
      study and analyze two datasets where the population size is known, before
      considering a real example relating to a population of dolphins off northeast
      Scotland.

PMID- 18047535
TI  - Inference for kappas for longitudinal study data: applications to sexual health
      research.
AB  - Analysis of instrument reliability and rater agreement is used in a wide range of
      behavioral, medical, psychosocial, and health-care-related research to assess
      psychometric properties of instruments, consensus in disease diagnoses, fidelity
      of psychosocial intervention, and accuracy of proxy outcomes. For categorical
      outcomes, Cohen's kappa is the most widely used index of agreement and
      reliability. In many modern-day applications, data are often clustered, making
      inference difficult to perform using existing methods. In addition, as
      longitudinal study designs become increasingly popular, missing data have become
      a serious issue, and the lack of methods to systematically address this problem
      has hampered the progress of research in the aforementioned fields. In this
      article, we develop a novel approach based on a new class of kappa estimates to
      tackle the complexities involved in addressing missing data and other related
      issues arising from a general multirater and longitudinal data setting. The
      approach is illustrated with real data in sexual health research.

PMID- 18047536
TI  - Multivariate Markov process models for the transmission of methicillin-resistant
      Staphylococcus aureus in a hospital ward.
AB  - Methicillin-resistant Staphylococcus Aureus (MRSA) is a pathogen that continues
      to be of major concern in hospitals. We develop models and computational schemes
      based on observed weekly incidence data to estimate MRSA transmission parameters.
      We extend the deterministic model of McBryde, Pettitt, and McElwain (2007,
      Journal of Theoretical Biology 245, 470-481) involving an underlying population
      of MRSA colonized patients and health-care workers that describes, among other
      processes, transmission between uncolonized patients and colonized health-care
      workers and vice versa. We develop new bivariate and trivariate Markov models to
      include incidence so that estimated transmission rates can be based directly on
      new colonizations rather than indirectly on prevalence. Imperfect sensitivity of
      pathogen detection is modeled using a hidden Markov process. The advantages of
      our approach include (i) a discrete valued assumption for the number of colonized
      health-care workers, (ii) two transmission parameters can be incorporated into
      the likelihood, (iii) the likelihood depends on the number of new cases to
      improve precision of inference, (iv) individual patient records are not required,
      and (v) the possibility of imperfect detection of colonization is incorporated.
      We compare our approach with that used by McBryde et al. (2007) based on an
      approximation that eliminates the health-care workers from the model, uses Markov
      chain Monte Carlo and individual patient data. We apply these models to MRSA
      colonization data collected in a small intensive care unit at the Princess
      Alexandra Hospital, Brisbane, Australia.

PMID- 18047537
TI  - Optimal observation times in experimental epidemic processes.
AB  - This article describes a method for choosing observation times for stochastic
      processes to maximise the expected information about their parameters. Two
      commonly used models for epidemiological processes are considered: a simple death
      process and a susceptible-infected (SI) epidemic process with dual sources for
      infection spreading within and from outwith the population. The search for the
      optimal design uses Bayesian computational methods to explore the joint parameter
      data-design space, combined with a method known as moment closure to approximate
      the likelihood to make the acceptance step efficient. For the processes
      considered, a small number of optimally chosen observations are shown to yield
      almost as much information as much more intensively observed schemes that are
      commonly used in epidemiological experiments. Analysis of the simple death
      process allows a comparison between the full Bayesian approach and locally
      optimal designs around a point estimate from the prior based on asymptotic
      results. The robustness of the approach to misspecified priors is demonstrated
      for the SI epidemic process, for which the computational intractability of the
      likelihood precludes locally optimal designs. We show that optimal designs
      derived by the Bayesian approach are similar for observational studies of a
      single epidemic and for studies involving replicated epidemics in independent
      subpopulations. Different optima result, however, when the objective is to
      maximise the gain in information based on informative and non-informative priors:
      this has implications when an experiment is designed to convince a naive or
      sceptical observer rather than consolidate the belief of an informed observer.
      Some extensions to the methods, including the selection of information criteria
      and extension to other epidemic processes with transition probabilities, are
      briefly addressed.

PMID- 18047538
TI  - Haplotype-based regression analysis and inference of case-control studies with
      unphased genotypes and measurement errors in environmental exposures.
AB  - It is widely believed that risks of many complex diseases are determined by
      genetic susceptibilities, environmental exposures, and their interaction.
      Chatterjee and Carroll (2005, Biometrika 92, 399-418) developed an efficient
      retrospective maximum-likelihood method for analysis of case-control studies that
      exploits an assumption of gene-environment independence and leaves the
      distribution of the environmental covariates to be completely nonparametric.
      Spinka, Carroll, and Chatterjee (2005, Genetic Epidemiology 29, 108-127) extended
      this approach to studies where certain types of genetic information, such as
      haplotype phases, may be missing on some subjects. We further extend this
      approach to situations when some of the environmental exposures are measured with
      error. Using a polychotomous logistic regression model, we allow disease status
      to have K+ 1 levels. We propose use of a pseudolikelihood and a related EM
      algorithm for parameter estimation. We prove consistency and derive the resulting
      asymptotic covariance matrix of parameter estimates when the variance of the
      measurement error is known and when it is estimated using replications.
      Inferences with measurement error corrections are complicated by the fact that
      the Wald test often behaves poorly in the presence of large amounts of
      measurement error. The likelihood-ratio (LR) techniques are known to be a good
      alternative. However, the LR tests are not technically correct in this setting
      because the likelihood function is based on an incorrect model, i.e., a
      prospective model in a retrospective sampling scheme. We corrected standard
      asymptotic results to account for the fact that the LR test is based on a
      likelihood-type function. The performance of the proposed method is illustrated
      using simulation studies emphasizing the case when genetic information is in the
      form of haplotypes and missing data arises from haplotype-phase ambiguity. An
      application of our method is illustrated using a population-based case-control
      study of the association between calcium intake and the risk of colorectal
      adenoma.

PMID- 18047539
TI  - Association between genetic variants in the IL-23R gene and early-onset Crohn's
      disease: results from a case-control and family-based study among Canadian
      children.
AB  - BACKGROUND AND OBJECTIVES: Interleukin (IL)-23 is a key regulator of inflammation
      and influences the activities of T-helper 17 (Th-17) lymphocytes. Recent reports
      indicate that variants in the gene coding for its receptor (IL-23R) are strongly
      associated with Crohn's disease (CD). We investigated whether DNA variants in the
      IL-23R gene determine susceptibility for CD in Canadian children. DESIGN AND
      METHODS: A case-control and case-parent trio design was implemented at three
      pediatric centers across Canada. Cases of CD (</=20 yr) along with their parents
      and controls were recruited. DNA samples were collected and genotyped for 10
      single nucleotide polymorphisms (SNPs) in the IL-23R gene and three common SNPs
      in the CARD15 gene. Transmission disequilibrium-based tests were applied to the
      case-parent data and logistic regression models to the case-control data to study
      the association between the SNPs and CD. RESULTS: A total of 259 CD cases, 139
      controls, and 232 families (167 trios and 65 dyads) were studied. The mean age at
      diagnosis was 13.3 yr (range 2.6-20 yr). The majority of the patients were
      Caucasian. Case-control analysis revealed significant associations with three
      SNPs (rs1004819, rs7517847, and rs11209026 [R381Q]) and borderline nonsignificant
      associations with three other SNPs (rs10489629, rs10889697, and rs11465804) in
      the IL-23R gene. Having any CARD15 variant was associated with a significant risk
      for CD (P < 0.0001). Analyses of case-parent data confirmed the findings from the
      case-control analysis including significant associations with the R381Q SNP (P=
      0.002). The common variant in this SNP conferred risk for CD. These associations
      were largely independent of the CARD15 gene. CONCLUSIONS: Our findings confirm
      recently reported genome-wide associations between the IL-23R gene and CD. They
      suggest that the gene is also associated with pediatric-onset CD among Canadian
      children.

PMID- 18047540
TI  - ATG16L1 and IL23R are associated with inflammatory bowel diseases but not with
      celiac disease in the Netherlands.
AB  - BACKGROUND: Inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative
      colitis (UC)--and celiac disease are intestinal inflammatory disorders with a
      complex genetic background. Recently, two novel genes were found to be associated
      with IBD susceptibility. One, an uncommon coding variant (rs11209026) in the gene
      encoding for the interleukin-23 receptor (IL23R), conferred strong protection
      against CD. The other, rs2241880 in the autophagy-related 16-like 1 gene
      (ATG16L1), was associated with CD. We performed a case-control study for the
      association of IBD with IL23R and ATG16L1 in a Dutch cohort. We also looked at
      the association of IL23R and ATG16L1 with celiac disease. METHODS: Five hundred
      eighteen Dutch white IBD patients (311 CD and 207 UC, including 176 trios of
      patients with both parents), 508 celiac disease patients, and 893 healthy
      controls were studied for association with the rs11209026 (IL23R) and rs2241880
      (ATG16L1) single nucleotide polymorphisms (SNP). RESULTS: The rs11209026 SNP in
      IL23R had a protective effect for IBD in the case-control analysis (odds ratio
      [OR] 0.19, 95% confidence interval [CI] 0.10-0.37, P= 6.6E-09). Both CD (OR 0.14,
      CI 0.06-0.37, P= 3.9E-07) and UC (OR 0.33, CI 0.15-0.73, P= 1.4E-03) were
      associated with IL23R. For ATG16L1, the rs2241880 SNP was associated with CD
      susceptibility (OR 1.36, CI 1.12-1.66, P= 0.0017). The population-attributable
      risk of carrying allele G is 0.24 and is 0.19 for homozygosity for allele G in
      CD. No association was found between IL23R or ATG16L1 and celiac disease.
      CONCLUSIONS: We confirmed the association of IL23R and ATG16L1 with CD
      susceptibility and also the association of IL23R with UC. We found IL23R and
      ATG16L1 were not associated with celiac disease susceptibility.

PMID- 18047541
TI  - Gastroparesis-related hospitalizations in the United States: trends,
      characteristics, and outcomes, 1995-2004.
AB  - OBJECTIVES: Gastroparesis is an increasingly recognized disorder. Its prevalence
      in the United States is unknown. We examined the trends, characteristics, and
      outcomes of gastroparesis-related hospitalizations during 1995-2004. METHODS: The
      publicly available Healthcare Cost and Utilization Project (HCUP) Nationwide
      Inpatient Sample (NIS) comprises a nationally representative sample of 5-8
      million hospitalizations per year. Gastroparesis-related hospitalizations were
      identified using the International Classification of Diseases (ICD-9) code 536.3
      and compared with other hospitalizations. Multivariate regressions were used to
      compare for differences in the outcomes including length of stay, total charges,
      and in-hospital deaths. RESULTS: Hospitalizations with gastroparesis as the
      primary diagnosis increased from 3,977 in 1995 to 10,252 in 2004 (+158%) and
      hospitalizations with gastroparesis as the secondary diagnosis increased from
      56,726 to 134,146 (+136%). These compared to smaller changes in diabetes-related
      hospitalizations (+53%), all hospitalizations (+13%), and hospitalizations with
      gastroesophageal reflux disease (GERD), gastric ulcer, gastritis, or nonspecific
      nausea/vomiting as the primary diagnosis (-3% to +76%). Of the five upper
      gastrointestinal conditions studied as the primary diagnosis, gastroparesis had
      the longest length of stay (+15.4% to +66.2%, all P < 0.001) and the highest or
      second highest total charges (-7.2% to +60.6%, all P < 0.01) in 2004, with
      similar results in 1995. CONCLUSIONS: The number of gastroparesis-related
      hospitalizations has been increasing in the United States, suggesting an
      increasing prevalence of gastroparesis. The economic impact of gastroparesis
      related hospitalizations is significant and increasing.

PMID- 18047542
TI  - Predictive factors of response to cyclosporine in steroid-refractory ulcerative
      colitis.
AB  - OBJECTIVES: Cyclosporine is an effective rescue therapy in steroid-refractory
      ulcerative colitis (UC) and may avoid immediate colectomy. However, the
      individual's response to cyclosporine is poorly predictable. The aim of this
      study was to identify predictive factors of the response to cyclosporine in
      steroid-refractory UC. METHODS: One hundred thirty-five patients with steroid
      refractory UC, admitted consecutively between 1992 and 2004, were included. Data
      were collected on the first day of the cyclosporine therapy. Colonoscopy was
      performed within 2 days preceding or following the cyclosporine treatment in 118
      patients for assessing the presence of severe endoscopic lesions. RESULTS: The
      actuarial rate of colectomy was 0.45 at 6 months. Cox analysis in the whole
      population selected three predictive criteria of colectomy: body temperature
      >37.5 degrees C (adjusted hazard ratio = 1.94, 95% confidence interval 1.51
      2.49), heart rate >90 bpm (1.86, 1.45-2.38), and C-reactive protein (CRP) >45
      mg/L (1.70, 1.34-2.16). In the 118 patients who underwent colonoscopy, the
      presence of severe endoscopic lesions was an independent predictive factor of
      colectomy (2.38, 1.80-3.14). Colonoscopy was decisive and changed the therapeutic
      decision in patients with one or two criteria: 71% of the patients with severe
      endoscopic lesions were colectomized versus 17% of the patients without severe
      endoscopic lesions (P < 0.001). Finally, the clinical, biological, and endoscopic
      criteria allowed the classification of the patients into two different groups
      (80%vs 20% colectomy at 6 months). CONCLUSION: In patients with steroid
      refractory UC, the combination of simple criteria is useful to predict the
      response to cyclosporine. Colonoscopy is crucial in patients with intermediate
      clinical and biological severity.

PMID- 18047544
TI  - Capsule endoscopy for screening for short-segment Barrett's esophagus.
AB  - BACKGROUND: The rise in the incidence of esophageal adenocarcinoma has led to the
      development of new methods to screen for the precursor lesion, Barrett's
      esophagus. AIM: To evaluate the potential role of esophageal capsule endoscopy in
      identifying the presence of short-segment Barrett's esophagus. METHODS: Patients
      with biopsy-proven short-segment Barrett's esophagus underwent esophageal capsule
      endoscopy. The images were reviewed by two expert observers with no knowledge of
      the purpose of the study. The data collected included transit time, quality of
      image, presence or absence of Z-line, Schatzki's ring, hiatal hernia, and
      Barrett's esophagus (long or short, definite or suspected). RESULTS: Twenty
      patients were studied; in 18, the capsule passed into the stomach. Barrett's
      esophagus was identified or suspected in eight cases (44%) by one observer and
      three (16%) by the second (P= 0.14). Although the Z-line was seen in the 18 cases
      that were qualified by both observers, there was an agreement in only six cases
      as to whether it was regular or irregular. Erosive gastroesophageal reflux
      disease (GERD) was scored as present in three and absent in six patients by both
      readers. Nonexisting feline esophagus, varices, and distal esophageal stricture
      were suspected in one patient each. CONCLUSIONS: Esophageal capsule endoscopy had
      a high interobserver variability and a low yield for short-segment Barrett's
      esophagus. Esophageal capsule endoscopy cannot be recommended for screening for
      short-segment Barrett's esophagus.

PMID- 18047543
TI  - New serological markers for inflammatory bowel disease are associated with
      earlier age at onset, complicated disease behavior, risk for surgery, and
      NOD2/CARD15 genotype in a Hungarian IBD cohort.
AB  - BACKGROUND: Antibodies to Saccharomyces cerevisiae (S. cerevisiae) (ASCA) and
      porin protein-C of Escherichia coli (anti-OmpC) are associated with disease
      phenotype and may be of diagnostic importance in inflammatory bowel diseases
      (IBD). Our aim was to determine whether a panel of new antibodies against
      bacterial proteins and carbohydrates could help differentiate among the various
      forms of IBD, and whether they were associated with particular clinical
      manifestations in a Hungarian cohort of IBD patients. METHODS: Six hundred fifty
      two well-characterized, unrelated, consecutive IBD patients (CD [Crohn's disease]
      557, men/women 262/295, duration 8.1 +/- 11.3 yr; ulcerative colitis [UC] 95,
      men/women 44/51, duration 8.9 +/- 9.8 yr) and 100 healthy and 48 non-IBD
      gastrointestinal (GI) controls were investigated. Sera were assayed for anti-OmpC
      and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside
      (ALCA), chitobioside (ACCA), and mannobioside (AMCA). TLR4 and NOD2/CARD15
      variants were tested by polymerase chain reaction/restriction fragment length
      polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by
      reviewing the patients' medical charts. RESULTS: Sixty-six percent of the CD
      patients had at least one of the investigated antibodies. Among glycan
      antibodies, gASCA or the combination of gASCA and atypical perinuclear
      antineutrophil cytoplasmic antibodies (pANCA) was most accurate for
      differentiating between CD and UC. ASCA and gASCA assays performed similarly.
      Increasing amount and level of antibody responses toward gASCA, ALCA, ACCA, AMCA,
      and OmpC were associated with more complicated disease behavior (P < 0.0001) and
      need for surgery in CD (P= 0.023). A serological dosage effect was also observed.
      gASCA and AMCA antibodies were associated with NOD2/CARD15, in addition to a gene
      dosage effect. No serotype-phenotype associations were found in UC. CONCLUSIONS:
      Antibody response to this new panel of serological markers was associated with
      complicated disease phenotype, NOD2/CARD15 genotype, and a need for surgery in
      this eastern European IBD cohort.

PMID- 18047545
TI  - Obstacles to colorectal cancer screening in Chinese: a study based on the health
      belief model.
AB  - BACKGROUND: Colorectal cancer (CRC) has emerged as the second most common cancer
      in Asia. This study uses the Health Belief Model (HBM) to examine the factors
      associated with the uptake of CRC testing. METHODS: A population-based telephone
      survey in which 1,004 randomly selected Chinese residents of Hong Kong aged
      between 30 and 65 yr were interviewed in 2006. Instruments were developed to
      measure the variables pertinent to the HBM, including perceived susceptibility,
      severity, benefit, barriers, and cues to action. The relationships of these
      predictors with CRC testing were examined using bivariate and multiple logistic
      regression analyses. RESULTS: Ten percent of the respondents had undertaken a CRC
      screening test. In the multiple logistic regression analyses, knowledge factors
      that were positively associated with CRC testing included knowledge of CRC
      symptoms (adjusted odds ratio [aOR] 3.33, 95% confidence interval [CI] 1.21-9.11)
      and knowledge of CRC risk factors (aOR 2.61, 95% CI 1.16-5.88). Five of the
      variables pertaining to the HBM were significant correlates of CRC testing
      perceived severity of CRC (aOR 0.28, 95% CI 0.13-0.65), perceived health and
      psychological barriers to CRC testing (aOR 0.42, 95% CI 0.21-0.84, 95% CI 0.21
      0.85), perceived access barriers to CRC testing (aOR 0.22, 95% CI 0.05-0.85),
      physician's recommendation (indicator of cues to action) (aOR 23.50, 95% CI 10.66
      51.80), and having health insurance (indicator of cues to action) (aOR 2.06, 95%
      CI 1.01-4.19). CONCLUSIONS: CRC testing compliance among this Asian population is
      low. Knowledge of CRC symptoms and risk factors are low. Perceived health,
      psychological, and access barriers to CRC testing are high. The physician's
      recommendation and having health insurance coverage significantly increase
      testing, but physicians mainly recommend patients with a family history of CRC
      for testing, and only around one-third of the population has health insurance.

PMID- 18047546
TI  - Detection of antisynthetic mannoside antibodies (ASigmaMA) reveals heterogeneity
      in the ASCA response of Crohn's disease patients and contributes to differential
      diagnosis, stratification, and prediction.
AB  - OBJECTIVES: Anti-S. cerevisiae mannan antibodies (ASCA) are human antibodies
      associated with Crohn's disease (CD) reacting with Saccharomyces cerevisiae (S.
      cerevisiae) mannan polymer. As mannan is a complex and variable repertoire of
      oligomannoses acting as epitopes, we chemically synthesized (Sigma) two major
      oligomannose epitopes, Man alpha-1,3 Man alpha-1,2 Man (SigmaMan3) and Man alpha
      1,3 Man alpha-1,2 Man alpha-1,2 Man (SigmaMan4), and then explored how
      antisynthetic mannoside antibodies (ASigmaMA) compare with ASCA as markers of CD.
      METHODS: The study involved different cohorts of CD and ulcerative colitis (UC)
      patients and healthy controls who had been studied previously in several medical
      centers in Europe, the United States, and North Africa to determine the clinical
      value of ASCA in terms of differential diagnosis, evolution of indeterminate
      colitis (IC), and serotype-phenotype correlations. The comparison of ASigmaMA and
      ASCA included a total of 1,365 subjects: 772 CD, 261 UC, 43 IC, and 289 controls.
      RESULTS: The specificity of ASigmaMA was similar to that of ASCA (89% vs 93%),
      although the sensitivity was lower (38% vs 55%). Unexpectedly, 24% of the CD
      patients who were negative for ASCA and/or other CD-associated serologic markers
      were positive for ASigmaMA. ASigmaMA were associated with colonic involvement in
      CD (odds ratio [OR] 1.609, 95% confidence interval [CI] 1.033-2.506, P = 0.03)
      and were 100% predictive of CD in patients with IC. CONCLUSIONS: ASigmaMA reveal
      the heterogeneity of the antioligomannose antibody response in CD patients and
      increase the sensitivity of CD diagnosis when combined with ASCA. The subset of
      ASCA-negative CD patients diagnosed by ASigmaMA had preferentially a colonic
      involvement, which confirms the high predictive value of ASigmaMA for determining
      IC evolution toward CD.

PMID- 18047547
TI  - An acquired factor V inhibitor associated with defective factor V function,
      storage and binding to multimerin 1.

PMID- 18047548
TI  - Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation
      assay to assess the bleeding phenotype.
AB  - INTRODUCTION: In some patients with mild hemophilia A, there are discrepancies
      between 1-stage (1-st) and 2-stage (2-st) factor VIII (FVIII) clotting assays,
      and also chromogenic assays for FVIII activity (FVIII:C). We examined whether
      thrombography could provide a better evaluation of the hemostatic status of these
      patients. METHODS: Two families with such discrepancies and markedly contrasting
      clinical histories were studied. Family X had no serious bleedings, in contrast
      to family Y. Sixty-one moderate/mild hemophiliacs without discrepancy and 15
      healthy subjects served as controls. Calibrated automated thrombography was
      performed with platelet-rich plasma after one freeze-thawing cycle and low tissue
      factor concentration. RESULTS: The chromogenic FVIII:C levels were higher (0.90
      +/- 0.15 and 0.47 +/- 0.13 IU mL(-1)) than the 1-st clotting ones (0.14 +/- 0.05
      and 0.10 +/- 0.05 IU mL(-1)) in family X and Y, respectively (P < 0.001). Mean
      endogenous thrombin potential (ETP) was 1579 +/- 359 nM min(-1) and 1060 +/- 450
      for healthy controls and hemophilic controls, respectively. For members of family
      X, the ETP values were 1188, 1317 and 2277 nM min(-1), whereas for those of
      family Y they ranged from 447 to 1122 nM min(-1). Two novel missense point
      mutations were evidenced: p.Ile369Thr in family X and p.Phe2127Ser in family Y.
      In family X, we postulate that the mutation is responsible for a delayed but non
      deleterious FVIII activation. CONCLUSIONS: Our results suggest that the
      hemostatic phenotype assessed by thrombography may be clinically relevant in
      moderate/mild hemophilic patients with discrepant FVIII:C results.

PMID- 18047549
TI  - Protein trafficking to apical organelles of malaria parasites - building an
      invasion machine.
AB  - Malaria is caused by four species of apicomplexan protozoa belonging to the genus
      Plasmodium. These parasites possess a specialized collection of secretory
      organelles called rhoptries, micronemes and dense granules (DGs) that in part
      facilitate invasion of host cells. The mechanism by which the parasite traffics
      proteins to these organelles as well as regulates their secretion has important
      implications for understanding the invasion process and may lead to development
      of novel intervention strategies. In this review, we focus on emerging data about
      trafficking signals, mechanisms of biogenesis and secretion. At least some of
      these are conserved in higher eukaryotes, suggesting that rhoptries, micronemes
      and DGs are related to organelles such as secretory lysosomes that are well known
      to mainstream cell biologists.

PMID- 18047550
TI  - Oestradiol rapidly enhances spontaneous glycinergic synaptic inhibition of
      hypoglossal motoneurones.
AB  - Whereas oestradiol is well-known to facilitate excitatory glutamatergic synaptic
      transmission, its effects on fast inhibitory neurotransmission are not as well
      established. Possible acute modulation of the spontaneous glycinergic synaptic
      activity by oestradiol was investigated in voltage-clamped hypoglossal
      motoneurones by whole-cell patch-clamp recording in rat brainstem slices. The
      spontaneous glycinergic synaptic activity was continuously recorded in each
      neurone under control conditions, during 12-20 min of perfusion with 17beta
      oestradiol and during washing. When oestradiol was diluted in ethanol, the
      control solution contained the same amount of ethanol. At 100 nM, oestradiol
      markedly increased the frequency of the total spontaneous glycinergic activity.
      Similar experiments were performed after blockade of action potentials by
      tetrodotoxin, aiming to isolate miniature glycinergic synaptic currents.
      Oestradiol increased the frequency of glycinergic miniatures in most slices, in
      some cases within less than 1 min. In some slices, oestradiol also favoured the
      occurrence of glycinergic miniatures of large amplitude. These effects were
      slowly reversible during washing. At 1 nm, oestradiol still increased the
      frequency of glycinergic miniatures. The results were confirmed in the absence of
      ethanol by using water-soluble cyclodextrin-encapsulated oestradiol. In these
      experiments, the control solution contained the same amount of (2-hydroxypropyl)
      beta-cyclodextrin as the oestradiol-containing solution. In addition, prolonged
      control recordings were performed without applying oestradiol to check the
      stability of the glycinergic synaptic activity during prolonged whole-cell
      recordings. The results show, for the first time, that, within a few minutes,
      oestradiol can enhance the spontaneous synaptic release of a major inhibitory
      transmitter, glycine.

PMID- 18047551
TI  - Acupuncture in polycystic ovary syndrome: current experimental and clinical
      evidence.
AB  - This review describes the aetiology and pathogenesis of polycystic ovary syndrome
      (PCOS) and evaluates the use of acupuncture to prevent and reduce symptoms
      related with PCOS. PCOS is the most common female endocrine disorder and it is
      strongly associated with hyperandrogenism, ovulatory dysfunction and obesity.
      PCOS increases the risk for metabolic disturbances such as hyperinsulinaemia and
      insulin resistance, which can lead to type 2 diabetes, hypertension and an
      increased likelihood of developing cardiovascular risk factors and impaired
      mental health later in life. Despite extensive research, little is known about
      the aetiology of PCOS. The syndrome is associated with peripheral and central
      factors that influence sympathetic nerve activity. Thus, the sympathetic nervous
      system may be an important factor in the development and maintenance of PCOS.
      Many women with PCOS require prolonged treatment. Current pharmacological
      approaches are effective but have adverse effects. Therefore, nonpharmacological
      treatment strategies need to be evaluated. Clearly, acupuncture can affect PCOS
      via modulation of endogenous regulatory systems, including the sympathetic
      nervous system, the endocrine and the neuroendocrine system. Experimental
      observations in rat models of steroid-induced polycystic ovaries and clinical
      data from studies in women with PCOS suggest that acupuncture exert long-lasting
      beneficial effects on metabolic and endocrine systems and ovulation.

PMID- 18047552
TI  - Affective and adrenocorticotrophic responses to photoperiod in Wistar rats.
AB  - The present study tested the hypothesis that seasonal intervals of exposure to
      modest changes in photoperiod, typical of those experienced by humans living in
      temperate latitudes (10-14 h light/day), engage changes in emotional behaviour of
      Wistar rats, a commonly-used animal model for investigations of affective
      physiology. Short day lengths (<or= 12 h light/day) induced behavioural despair
      in a forced-swim test, exploratory anxiety in an open field arena, and anhedonia
      in a two-bottle sucrose preference task, relative to longer day lengths. Plasma
      adrenocorticotrophic hormone was lower in short-day relative to long-day rats,
      but testosterone and corticosterone concentrations were comparable across
      treatments. In common with animals that engage reproductive responses to day
      length, reproductively nonresponsive mammals such as Wistar rats exhibit changes
      in affective state following small changes in day length. Wistar rats may provide
      an animal model for the study of seasonal mood regulation because the
      neuroendocrine, depressive, anxious and anhedonic responses of Wistar rats to
      short days bear similarities to those observed in some human populations.
      Standard laboratory husbandry practices (exposure to a 12 : 12 h light/dark
      cycle) may inadvertently deliver a chronic background depressive and anxiogenic
      stimulus.

PMID- 18047553
TI  - Chronic osmotic stimuli increase salusin-beta-like immunoreactivity in the rat
      hypothalamo-neurohypophyseal system: possible involvement of salusin-beta on
      [Ca2+]i increase and neurohypophyseal hormone release from the axon terminals.
AB  - Salusin-alpha and -beta were recently discovered as bioactive endogenous
      peptides. In the present study, we investigated the effects of chronic osmotic
      stimuli on salusin-beta-like immunoreactivity (LI) in the rat hypothalamo
      neurohypophyseal system. We examined the effects of salusin-beta on synaptic
      inputs to the rat magnocellular neurosecretory cells (MNCs) of the supraoptic
      nucleus (SON) and neurohypophyseal hormone release from both freshly dissociated
      SONs and neurohypophyses in rats. Immunohistochemical studies revealed that
      salusin-beta-LI neurones and fibres were markedly increased in the SON and the
      magnocellular division of the paraventricular nucleus after chronic osmotic
      stimuli resulting from salt loading for 5 days and dehydration for 3 days.
      Salusin-beta-LI fibres and varicosities in the internal zone of the median
      eminence and the neurohypophysis were also increased after osmotic stimuli. Whole
      cell patch-clamp recordings from rat SON slice preparations showed that salusin
      beta did not cause significant changes in the excitatory and inhibitory
      postsynaptic currents of the MNCs. In vitro hormone release studies showed that
      salusin-beta evoked both arginine vasopressin (AVP) and oxytocin release from the
      neurohypophysis, but not the SON. In our hands, in the neurohypophysis, a
      significant release of AVP and oxytocin was observed only at concentrations from
      100 nm and above of salusin-beta. Low concentrations below 100 nm were
      ineffective both on AVP and oxytocin release. We also measured intracellular
      calcium ([Ca(2+)](i)) increase induced by salusin-beta on freshly-isolated single
      nerve terminals from the neurohypophysis devoid of pars intermedia. Furthermore,
      this salusin-beta-induced [Ca(2+)](i) increase was blocked in the presence of
      high voltage activated Ca(2+)channel blockers. Our results suggest that salusin
      beta may be involved in the regulation of body fluid balance by stimulating
      neurohypophyseal hormone release from nerve endings by an autocrine/paracrine
      mechanism.

PMID- 18047554
TI  - Changes in the brain serotonin satiety system in transgenic rats lacking brain
      angiotensinogen.
AB  - In transgenic rats, TGR(ASrAOGEN)680, with reduced glial expression of
      angiotensinogen, changes in brain angiotensinogen are associated with reductions
      in serotonin (5-HT) content and/or 5-HT metabolism as determined in various brain
      regions, including the hypothalamus. These rats showed an anxious phenotype upon
      a first behavioural screen. The present study aimed to extend the search for
      functional consequences of changes in brain 5-HT with respect to feeding
      behaviour in these transgenic rats. In feeding experiments, rats were treated
      with the anorectic drug fenfluramine to probe for functional changes in the
      serotonergic satiety system. Fenfluramine (0.3 mg/kg, i.p.) reduced food intake
      in TGR(ASrAOGEN)680 rats whereas the minimal effective dose in wild-type rats was
      3 mg/kg, i.p. Although, in the cortex, no differences were apparent in the
      expression of serotonin 5-HT(1A), 5-HT(1B), 5-HT(2C) receptor and 5-HT
      transporter mRNAs between TGR(ASrAOGEN)680 and wild-type rats, the expression of
      mRNAs for the 5-HT(2C) receptor and 5-HT transporter mRNA were significantly
      higher in the hypothalamus of TGR(ASrAOGEN)680 rats compared to wild-type rats.
      No differences were found in the mRNA levels for hypothalamic 5-HT(1A) and 5
      HT(1B) receptors between TGR(ASrAOGEN)680 and wild-type rats. Taken together,
      these findings suggest that the transgenic effect on the brain 5-HT system is
      paralleled by functional changes of the serotonergic feeding system.

PMID- 18047555
TI  - Presence of corticotrophin-releasing factor and/or tyrosine hydroxylase in cells
      of a neural brain-testicular pathway that are labelled by a transganglionic
      tracer.
AB  - Our laboratory has shown that male testosterone levels are not solely controlled
      by the release of hypothalamic gonadotrophin-releasing hormone and pituitary
      luteinising hormone, but are also regulated by a multisynaptic pathway connecting
      the brain and the testis that interferes with the testosterone response to
      gonadotrophins. This pathway, which is independent of the pituitary gland, is
      activated by an i.c.v. injection of either the stress-related peptide
      corticotrophin-releasing factor (CRF) or of beta-adrenoceptor agonists, both of
      which alter androgen release and decrease levels of the peripheral-type
      benzodiazepine receptor and the steroidogenic acute regulatory protein within
      Leydig cells. Our original studies used the retrograde transganglionic tracer
      pseudorabies virus (PRV) to map progression of the virus from the testes to upper
      brain levels. The present study aimed to extend this work by identifying the
      regions where CRF and catecholamine neurones represented components of the stress
      activated, brain-testicular pathway that prevents testosterone increases. To this
      end, anaesthetised adult male rats received an intra-testicular injection of PRV.
      Using immunofluorescence, we identified co-labelling of PRV and either CRF or
      tyrosine hydroxylase (TH), the enzyme responsible for biogenic amine synthesis.
      Co-labelling of PRV and CRF was found in the bed nucleus of the stria terminalis,
      the paraventricular nucleus of the hypothalamus (PVN) and the central amygdala.
      Co-labelling of PRV and TH was found in the PVN, substantia nigra, A7/Kolliker
      Fuse area, area of A5, locus coeruleus, nucleus of solitary tract, area of C3,
      area of C2 and the area of C1/A1. These results indicate that most cell groups of
      the ventral noradrenergic pathway have neurones that are a part of the brain
      testicular pathway. This suggests that the stress hormones CRF and catecholamines
      may act as neurotransmitters that signal the pathway to inhibit increases in
      plasma testosterone levels.

PMID- 18047557
TI  - FUSCA3 from barley unveils a common transcriptional regulation of seed-specific
      genes between cereals and Arabidopsis.
AB  - Accumulation of storage compounds in the embryo and endosperm of developing seeds
      is a highly regulated process that allows seedling growth upon germination until
      photosynthetic capacity is acquired. A critical regulatory element in the
      promoters of seed storage protein (SSP) genes from dicotyledonous species is the
      RY box, a target of B3-type transcription factors. However, the functionality of
      this motif in the transcriptional regulation of SSP genes from cereals has not
      been fully established. We report here the identification and molecular
      characterization of barley FUSCA3, a B3-type transcription factor as yet
      uncharacterized in monocotyledonous plants. Our results show that both the barley
      and Arabidopsis FUS3 genes maintain a conserved functionality for the regulation
      of SSP genes and anthocyanin biosynthesis in these two distantly related
      phylogenetic groups. Complementation of the loss-of-function mutant fus3 in
      Arabidopsis by the barley HvFus3 gene resulted in restored transcription from the
      At2S3 gene promoter and normal accumulation of anthocyanins in the seed. In
      barley, HvFUS3 participates in transcriptional activation of the endosperm
      specific genes Hor2 and Itr1. HvFUS3, which specifically binds to RY boxes in
      EMSA experiments, trans-activates Hor2 and Itr1 promoters containing intact RY
      boxes in transient expression assays in developing endosperms. Mutations in the
      RY boxes abolished the HvFUS3-mediated trans-activation. HvFus3 transcripts
      accumulate in the endosperm and in the embryo of developing seeds, peaking at mid
      maturation phase. Remarkably, HvFUS3 interacts with the Opaque2-like bZIP factor
      BLZ2 in yeast, and this interaction is essential for full trans-activation of the
      seed-specific genes in planta.

PMID- 18047556
TI  - Identification of metabolic and biomass QTL in Arabidopsis thaliana in a parallel
      analysis of RIL and IL populations.
AB  - Plant growth and development are tightly linked to primary metabolism and are
      subject to natural variation. In order to obtain an insight into the genetic
      factors controlling biomass and primary metabolism and to determine their
      relationships, two Arabidopsis thaliana populations [429 recombinant inbred lines
      (RIL) and 97 introgression lines (IL), derived from accessions Col-0 and C24]
      were analyzed with respect to biomass and metabolic composition using a mass
      spectrometry-based metabolic profiling approach. Six and 157 quantitative trait
      loci (QTL) were identified for biomass and metabolic content, respectively. Two
      biomass QTL coincide with significantly more metabolic QTL (mQTL) than
      statistically expected, supporting the notion that the metabolic profile and
      biomass accumulation of a plant are linked. On the same basis, three out the six
      biomass QTL can be simulated purely on the basis of metabolic composition. QTL
      based on analysis of the introgression lines were in substantial agreement with
      the RIL-based results: five of six biomass QTL and 55% of the mQTL found in the
      RIL population were also found in the IL population at a significance level of P
      < or = 0.05, with >80% agreement on the allele effects. Some of the differences
      could be attributed to epistatic interactions. Depending on the search
      conditions, metabolic pathway-derived candidate genes were found for 24-67% of
      all tested mQTL in the database AraCyc 3.5. This dataset thus provides a
      comprehensive basis for the detection of functionally relevant variation in known
      genes with metabolic function and for identification of genes with hitherto
      unknown roles in the control of metabolism.

PMID- 18047558
TI  - Integrative functional genomics of salt acclimatization in the model legume Lotus
      japonicus.
AB  - The model legume Lotus japonicus was subjected to non-lethal long-term salinity
      and profiled at the ionomic, transcriptomic and metabolomic levels. Two
      experimental designs with various stress doses were tested: a gradual step
      acclimatization and an initial acclimatization approach. Ionomic profiling by
      inductively coupled plasma/atomic emission spectrometry (ICP-AES) revealed salt
      stress-induced reductions in potassium, phosphorus, sulphur, zinc and molybdenum.
      Microarray profiling using the Lotus Genechip allowed the identification of 912
      probesets that were differentially expressed under the acclimatization regimes.
      Gas chromatography/mass spectrometry-based metabolite profiling identified 147
      differentially accumulated soluble metabolites, indicating a change in metabolic
      phenotype upon salt acclimatization. Metabolic changes were characterized by a
      general increase in the steady-state levels of many amino acids, sugars and
      polyols, with a concurrent decrease in most organic acids. Transcript and
      metabolite changes exhibited a stress dose-dependent response within the range of
      NaCl concentrations used, although threshold and plateau behaviours were also
      observed. The combined observations suggest a successive and increasingly global
      requirement for the reprogramming of gene expression and metabolic pathways to
      maintain ionic and osmotic homeostasis. A simple qualitative model is proposed to
      explain the systems behaviour of plants during salt acclimatization.

PMID- 18047559
TI  - Agonist- and competitive antagonist-induced movement of loop 5 on the alpha
      subunit of the neuronal alpha4beta4 nicotinic acetylcholine receptor.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels
      that rapidly convert a chemical signal into an electrical signal. Although the
      structure of the nAChR is quite well described, the coupling between agonist
      binding and channel gating is still under debate. In this study, we probed local
      conformational transitions on the neuronal alpha4beta4 nAChR by specifically
      tethering a conformation-sensitive fluorescent dye on alphaG98C located on loop 5
      (L5), and simultaneously monitoring fluorescence intensity and current after
      expression in Xenopus oocytes. The potency of acetylcholine (ACh) was
      significantly higher in the cysteine mutant and further increased upon
      tetramethylrhodamine-6-maleimide labeling, suggesting a role of L5 in binding or
      gating. Structural reorganizations of L5 were shown to occur upon activation, as
      revealed by the fluorescence intensity increase during ACh exposure. Fluorescence
      changes were also detected at ACh concentrations lower than needed for current
      activation, suggesting a movement of L5 for a closed, resting or desensitized
      state. The competitive antagonist dihydro-beta-erythroidine also induced a
      movement of L5 although at concentrations significantly higher than needed for
      current inhibition. Consequently L5, located inside the lumen of the pentamer,
      plays a role in both activation and inhibition of the nAChR.

PMID- 18047560
TI  - Photoreceptor-specific expression, light-dependent localization, and
      transcriptional targets of the zinc-finger protein Yin Yang 1 in the chicken
      retina.
AB  - The zinc-finger transcription factor Yin Yang 1 (YY1) is a multifunctional
      protein that plays a critical role in embryonic development. Although it has been
      shown to play a role in eye development, its expression in the retina was not
      previously described. Here, we investigated YY1 expression in chicken tissues and
      we identified the neural retina as one of the tissues with highest YY1 protein
      levels. Immunohistochemical detection of YY1 in the retina revealed a clear-cut
      photoreceptor specificity and day/night differences in the cytoplasmic
      localization of the protein. YY1 was also present at high concentration in the
      nuclei of some photoreceptors. Gel-shift assays indicated YY1 bound to regulatory
      regions of several genes specifically expressed in photoreceptors. One of these
      genes, hydroxyindole-O-methyltransferase (EC 2.1.1.4), encodes the last enzyme of
      the melatonin synthesis pathway. Although over-expression of chicken YY1 was not
      sufficient to activate the chicken hydroxyindole-O-methyltransferase promoter in
      HEK293 cells, the YY1-binding site contained in this promoter was clearly
      required for full transcriptional activity in chicken embryonic retinal cells.
      These results suggest a role of YY1 in regulating the melatoninergic function of
      retinal photoreceptors.

PMID- 18047561
TI  - BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1
      knockout mice.
AB  - Stress can cause damage and atrophy of neurons in the hippocampus by deregulating
      the expression of neurotrophic factors that promote neuronal plasticity. The
      endocannabinoid system represents a physiological substrate involved in
      neuroprotection at both cellular and emotional levels. The lack of CB1 receptor
      alters neuronal plasticity and originates an anxiety-like phenotype in mice. In
      the present study, CB1 knockout mice exhibited an augmented response to stress
      revealed by the increased despair behavior and corticosterone levels showed in
      the tail suspension test and decreased brain derived neurotrophic factor (BDNF)
      levels in the hippocampus. Interestingly, local administration of BDNF in the
      hippocampus reversed the increased despair behavior of CB1 knockout mice,
      confirming the crucial role played by BDNF on the emotional impairment of these
      mutants. The neurotrophic deficiency seems to be specific for BDNF as no
      differences were found in the levels of nerve growth factor and NT-3, two
      additional neurotrophic factors. Moreover, BDNF impairment is not related to the
      activity of its specific tyrosine kinase receptor or the activity of the
      transcription factor cAMP responsive element binding. These results suggest that
      the lack of CB1 receptor originates an enhanced response to stress and deficiency
      in neuronal plasticity by decreasing BDNF levels in the hippocampus that lead to
      impairment in the responses to emotional disturbances.

PMID- 18047562
TI  - Simvastatin prevents the inflammatory process and the dopaminergic degeneration
      induced by the intranigral injection of lipopolysaccharide.
AB  - Anti-inflammatory strategies have attracted much interest for their potential to
      prevent further deterioration of Parkinson's disease. Recent experimental and
      clinical evidence indicate that statins - extensively used in medical practice as
      effective lipid-lowering agents - have also anti-inflammatory effects. In this
      study, we investigated the influence of simvastatin on the degenerative process
      of the dopaminergic neurons of the rat following intranigral injection of
      lipopolysaccharide (LPS), a potent inductor of inflammation that we have
      previously used as an animal model of Parkinson's disease. We evaluated TH
      positive neurons, astroglial, and microglial populations and found that
      simvastatin prevented the inflammatory processes, as the induction of interleukin
      1beta, tumor necrosis factor-alpha, and iNOS and the consequent dopaminergic
      degeneration induced by LPS. Moreover, simvastatin produced the activation of the
      neurotrophic factor BDNF, along with the prevention of the oxidative damage to
      proteins. Moreover, it also prevents the main changes produced by LPS on
      different mitogen-activated protein kinases, featured as increases of P-c-Jun N
      terminal protein kinase, P-extracellular signal-regulated kinase, p-38, and P
      glycogen synthase kinase and the decrease of the promotion of cell survival
      signals such as cAMP response element-binding protein and Akt. Our results
      suggest that statins could delay the progression of dopaminergic degeneration in
      disorders involving inflammatory processes.

PMID- 18047563
TI  - Is interleukin-1 genotyping useful for the clinical management of patients with
      atrophic body gastritis?
AB  - BACKGROUND: Atrophic body gastritis patients are at increased risk for gastric
      cancer. IL-1B/IL-1RN polymorphisms have been associated with gastric cancer
      susceptibility. The relationship between these polymorphisms and the long-term
      outcome of atrophic body gastritis patients is not known. AIM: To investigate
      whether the genotyping of IL-1B-511/IL-1RN polymorphisms is useful to
      characterize atrophic body gastritis patients at increased risk for gastric
      neoplasms. METHODS: IL-1B-511/IL-1RN polymorphisms were compared between 110
      atrophic body gastritis patients and 110 age- and gender-matched controls, and
      patients were followed up (median 4.1 years) according to a cohort study design.
      RESULTS: Genotype frequencies of IL-1B-511/IL-1RN were similar between patients
      and controls. Atrophic body gastritis patients harbouring the wild type of IL-1B
      511/IL-1RN polymorphisms were not different from those harbouring the
      proinflammatory pattern as far as regards gender, age, gastric cancer family
      history and metaplastic atrophy. Sixteen atrophic body gastritis patients
      developed a gastric neoplastic lesion at follow-up: eight were IL-1B-511-T
      carriers and eight were IL-1RN-allele-2 carriers. Harbouring the proinflammatory
      genotypes was not significantly associated with developing gastric neoplastic
      lesions. CONCLUSIONS: In atrophic body gastritis patients, IL-1B-511 and IL-1RN
      polymorphisms do not appear to be associated either with specific clinical,
      biochemical or histological features or with the development of gastric
      neoplastic lesions at long-term follow-up.

PMID- 18047564
TI  - Pre-operative transarterial chemoembolization for resectable hepatocellular
      carcinoma adversely affects post-operative patient outcome.
AB  - BACKGROUND: Long-term outcomes after hepatic resection for hepatocellular
      carcinoma are not satisfactory because of high recurrence rates. Aim To assess
      whether a single session of pre-operative transarterial chemoembolization affects
      post-operative outcome. METHODS: We analysed outcomes retrospectively in 334
      consecutive patients who underwent hepatic resection for hepatocellular
      carcinoma, initially judged resectable. Ninety-seven of these patients had each
      undergone a single session of pre-operative transarterial chemoembolization
      (transarterial chemoembolization + hepatic resection group), whereas 237 had not
      (hepatic resection group). RESULTS: Most clinicopathological characteristics were
      similar in the two groups. The overall survival rate was significantly higher in
      the hepatic resection than in the transarterial chemoembolization + hepatic
      resection group (P = 0.011), whereas their disease-free survival rates were
      comparable (P = 0.67). The overall and disease-free survival rates of the
      transarterial chemoembolization + hepatic resection group with incomplete tumour
      necrosis were significantly lower than those of the hepatic resection group (P <
      0.001 and P = 0.006, respectively). Multivariate analysis showed that pre
      operative transarterial chemoembolization, serum alpha-fetoprotein elevation
      (>1000 ng/mL), tumour size (>5 cm) and vascular invasion were independent risk
      factors for poor overall survival after hepatic resection. CONCLUSIONS: A single
      session of pre-operative transarterial chemoembolization for initially resectable
      hepatocellular carcinoma worsens overall survival rate. It may also increase the
      risk of tumour recurrence in patients who achieve incomplete tumour necrosis.

PMID- 18047565
TI  - Effect of proton pump inhibitors on markers of risk for high-grade dysplasia and
      oesophageal cancer in Barrett's oesophagus.
AB  - BACKGROUND: It has been shown that the presence on diagnosis of endoscopic
      macroscopic markers indicates a high-risk group for Barrett's oesophagus. AIM: To
      determine whether proton pump inhibitor therapy prior to diagnosis of Barrett's
      oesophagus influences markers for risk development of subsequent high-grade
      dysplasia/adenocarcinoma. METHODS: A review of all patients with Barrett's
      oesophagus entering a surveillance programme was undertaken. Five hundred and two
      patients diagnosed with Barrett's oesophagus were assessed on diagnosis for
      endoscopic macroscopic markers or low-grade dysplasia. Subsequent development of
      high-grade dysplasia/adenocarcinoma was documented. The relationship between the
      initiation of proton pump inhibitor therapy prior to the diagnosis of BE and the
      presence of macroscopic markers or low-grade dysplasia at entry was determined.
      RESULTS: Fourteen patients developed high-grade dysplasia/adenocarcinoma during
      surveillance. Patients who entered without prior proton pump inhibitor therapy
      were 3.4 times (95% CI: 1.98-5.85) more likely to have a macroscopic marker or
      low-grade dysplasia than those patients already on a proton pump inhibitor.
      CONCLUSIONS: Use of proton pump inhibitor therapy prior to diagnosis of Barrett's
      oesophagus significantly reduced the presence of markers used to stratify patient
      risk. Widespread use of proton pump inhibitors will confound surveillance
      strategies for patients with Barrett's oesophagus based on entry characteristics
      but is justified because of the lower risk of neoplastic progression.

PMID- 18047566
TI  - An unusual case of both upper and lower gastrointestinal bleeding in a kidney
      transplant recipient.
AB  - BACKGROUND: Tuberculosis (TB) is an uncommon opportunistic infection in
      immunocompromised patients. Extrapulmonary infection involving the intestine is
      rare and poses diagnostic difficulties. CASE REPORT: A 49-year-old man with IgA
      nephropathy underwent a kidney transplantation in 1996 and was put on
      cyclosporine, azathioprine, and steroid. He suffered from a recurrence of his
      primary kidney disease and had a gradual deterioration of renal function since
      1998. By 2005, he presented with an unusual gastrointestinal (GI) symptom with
      alternating signs of upper GI bleeding - melena - as well as lower GI bleeding
      with fresh rectal bleeding, resulting in severe anemia with hemoglobin level down
      to 5.0 g/dL. At the same time, his renal function further deteriorated and
      necessitated the initiation of dialysis while he was maintained on low-dose
      immunosuppressive drugs. Repeated upper and lower GI endoscopies were either
      unremarkable or revealed non-specific lesions. Symptoms persisted and exploratory
      laparotomy finally showed a 1 cm submucosal mass at the proximal jejunum and
      multiple inflammatory lesions at the terminal ileum. Segmental resection of the
      lesions was performed and confirmed TB infection. However, despite the initiation
      of anti-tuberculous treatment, the patient eventually died of complications.
      CONCLUSION: Diagnosing TB intestinal infection is a clinical challenge. A high
      index of suspicion in susceptible subjects is necessary, and early surgical
      intervention should always be considered when facing diagnostic uncertainties.

PMID- 18047567
TI  - Gac/Rsm signal transduction pathway of gamma-proteobacteria: from RNA recognition
      to regulation of social behaviour.
AB  - In many gamma-proteobacteria, the conserved GacS/GacA (BarA/UvrY) two-component
      system positively controls the expression of one to five genes specifying small
      RNAs (sRNAs) that are characterized by repeated unpaired GGA motifs but otherwise
      appear to belong to several independent families. The GGA motifs are essential
      for binding small, dimeric RNA-binding proteins of a single conserved family
      designated RsmA (CsrA). These proteins, which also occur in bacterial species
      outside the gamma-proteobacteria, act as translational repressors of certain
      mRNAs when these contain an RsmA/CsrA binding site at or near the Shine-Dalgarno
      sequence plus additional binding sites located in the 5' untranslated leader
      mRNA. Recent structural data have established that the RsmA-like protein RsmE of
      Pseudomonas fluorescens makes specific contacts with an RNA consensus sequence 5'
      (A)/(U)CANGGANG(U)/(A)-3' (where N is any nucleotide). Interaction with an
      RsmA/CsrA protein promotes the formation of a short stem supporting an ANGGAN
      loop. This conformation hinders access of 30S ribosomal subunits and hence
      translation initiation. The output of the Gac/Rsm cascade varies widely in
      different bacterial species and typically involves management of carbon storage
      and expression of virulence or biocontrol factors. Unidentified signal molecules
      co-ordinate the activity of the Gac/Rsm cascade in a cell population density
      dependent manner.

PMID- 18047568
TI  - Bistability and biofilm formation in Bacillus subtilis.
AB  - Biofilms of Bacillus subtilis consist of long chains of cells that are held
      together in bundles by an extracellular matrix of exopolysaccharide and the
      protein TasA. The exopolysaccharide is produced by enzymes encoded by the epsA-O
      operon and the gene encoding TasA is located in the yqxM-sipW-tasA operon. Both
      operons are under the control of the repressor SinR. Derepression is mediated by
      the antirepressor SinI, which binds to SinR with a 1:1 stoichiometry.
      Paradoxically, in medium promoting derepression of the matrix operons, the
      overall concentration of SinR in the culture greatly exceeded that of SinI. We
      show that under biofilm-promoting conditions sinI, which is under the control of
      the response regulator Spo0A, was expressed only in a small subpopulation of
      cells, whereas sinR was expressed in almost all cells. Activation of Spo0A is
      known to be subject to a bistable switch, and we infer that SinI reaches levels
      sufficient to trigger matrix production only in the subpopulation of cells in
      which Spo0A is active. Additionally, evidence suggests that sinI is expressed at
      intermediate, but not low or high, levels of Spo0A activity, which may explain
      why certain nutritional conditions are more effective in promoting biofilm
      formation than others.

PMID- 18047569
TI  - The Bacteroides fragilis transcriptome response to oxygen and H2O2: the role of
      OxyR and its effect on survival and virulence.
AB  - The intestinal anaerobic symbiont, Bacteroides fragilis, is highly aerotolerant
      and resistant to H(2)O(2). Analysis of the transcriptome showed that expression
      of 45% of the genome was significantly affected by oxidative stress. The gene
      expression patterns suggested that exposure to oxidative stress induced an acute
      response to rapidly minimize the immediate effects of reactive oxygen species,
      then upon extended exposure a broad metabolic response was induced. This
      metabolic response induced genes encoding enzymes that can supply reducing power
      for detoxification and restore energy-generating capacity. An integral aspect of
      the metabolic response was downregulation of genes related to translation and
      biosynthesis which correlated with decreased growth and entry into a stationary
      phase-like growth state. Examination of oxyR mutants showed that they were
      impaired for the acute response and they induced the expanded metabolic response
      with only minimal exposure to stress. The oxyR mutants were more sensitive to
      oxidants in vitro and in vivo they were attenuated in an intra-abdominal abscess
      infection model. Aerotolerance and resistance to oxidative stress are
      physiological adaptations of B. fragilis to its environment that enhance survival
      in extra-intestinal sites and promote opportunistic infections.

PMID- 18047570
TI  - Co-ordinated regulation of gluconate catabolism and glucose uptake in
      Corynebacterium glutamicum by two functionally equivalent transcriptional
      regulators, GntR1 and GntR2.
AB  - Corynebacterium glutamicum is a Gram-positive soil bacterium that prefers the
      simultaneous catabolism of different carbon sources rather than their sequential
      utilization. This type of metabolism requires an adaptation of the utilization
      rates to the overall metabolic capacity. Here we show how two functionally
      redundant GntR-type transcriptional regulators, designated GntR1 and GntR2, co
      ordinately regulate gluconate catabolism and glucose uptake. GntR1 and GntR2
      strongly repress the genes encoding gluconate permease (gntP), gluconate kinase
      (gntK), and 6-phosphogluconate dehydrogenase (gnd) and weakly the pentose
      phosphate pathway genes organized in the tkt-tal-zwf-opcA-devB cluster. In
      contrast, ptsG encoding the EII(Glc) permease of the glucose phosphotransferase
      system (PTS) is activated by GntR1 and GntR2. Gluconate and glucono-delta-lactone
      interfere with binding of GntR1 and GntR2 to their target promoters, leading to a
      derepression of the genes involved in gluconate catabolism and reduced ptsG
      expression. To our knowledge, this is the first example for gluconate-dependent
      transcriptional control of PTS genes. A mutant lacking both gntR1 and gntR2 shows
      a 60% lower glucose uptake rate and growth rate than the wild type when
      cultivated on glucose as sole carbon source. This growth defect can be
      complemented by plasmid-encoded GntR1 or GntR2.

PMID- 18047571
TI  - Mapping a common interaction site used by Plasmodium falciparum Duffy binding
      like domains to bind diverse host receptors.
AB  - The Duffy binding-like (DBL) domain is a key adhesive module in Plasmodium
      falciparum, present in both erythrocyte invasion ligands (EBLs) and the large and
      diverse P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of
      cytoadherence receptors. DBL domains bind a variety of different host receptors,
      including intercellular adhesion molecule 1 (ICAM-1), a receptor interaction that
      may have a role in infected erythrocyte binding to cerebral blood vessels and
      cerebral malaria. In this study, we expressed the nearly full complement of
      DBLbeta-C2 domains from the IT4/25/5 (IT4) parasite isolate and showed that ICAM
      1-binding domains (DBLbeta-C2(ICAM-1)) were confined to group B and group C
      PfEMP1 proteins and were not present in group A, suggesting that ICAM-1 selection
      pressure differs between PfEMP1 groups. To further dissect the molecular
      determinants of binding, we modelled a DBLbeta-C2(ICAM-1) domain on a solved DBL
      structure and created alanine substitution mutants in two DBLbeta-C2(ICAM-1)
      domains. This analysis indicates that the DBLbeta-C2::ICAM-1 interaction maps to
      the equivalent glycan binding region of EBLs, and suggests a general model for
      how DBL domains evolve under dual selection for host receptor binding and immune
      evasion.

PMID- 18047572
TI  - Roles of amyloplasts and water deficit in root tropisms.
AB  - Directed growth of roots in relation to a moisture gradient is called
      hydrotropism. The no hydrotropic response (nhr1) mutant of Arabidopsis lacks a
      hydrotropic response, and shows a stronger gravitropic response than that of wild
      type (wt) in a medium with an osmotic gradient. Local application of abscisic
      acid (ABA) to seeds or root tips of nhr1 increased root downward growth,
      indicating the critical role of ABA in tropisms. Wt roots germinated and treated
      with ABA in this system were strongly gravitropic, even though they had almost no
      starch amyloplasts in the root-cap columella cells. Hydrotropically stimulated
      nhr1 roots, with or without ABA, maintained starch in the amyloplasts, as opposed
      to those of wt. Hence, the near-absence (wt) or abundant presence (nhr1) of
      starch granules does not influence the extent of downward gravitropism of the
      roots in an osmotic gradient medium. Starch degradation in the wt might help the
      root sustain osmotic stress and carry out hydrotropism, instead of reducing
      gravity responsiveness. nhr1 roots might be hydrotropically inactive because they
      maintain this starch reserve in the columella cells, sustaining both their turgor
      and growth, and in effect minimizing the need for hydrotropism and at least
      partially disabling its mechanism. We conclude that ABA and water stress are
      critical regulators of root tropic responses.

PMID- 18047573
TI  - No longer hungry in hospital: improving the hospital mealtime experience for
      older people through action research.
AB  - AIMS AND OBJECTIVES: This study aimed to improve the mealtime experience of older
      people in a hospital setting through helping staff to make changes to their
      clinical practice and the ward environment. BACKGROUND: Poor nutritional care has
      been a persistent and seemingly intractable problem for many years. METHODS: We
      used an action research design for the study, drawing on techniques from practice
      development to support the action phase of the work, including action learning,
      role modelling good practice and reflection. The ward context was explored at the
      beginning and end of the study using focus groups, interviews, observation and
      benchmarking. RESULTS: Ward staff made a number of changes to their nursing
      practice. The most significant was that all staff became engaged with,
      prioritized and were involved in the mealtime, ensuring that there was sufficient
      time and expertise available to assist patients with eating. CONCLUSIONS: This
      study demonstrates that it is possible to change nursing practice at mealtimes
      and that this change leads to improvements in patients' experience through
      ensuring they receive the help they need. Relevance to clinical practice.
      Although hospital mealtimes are frequently viewed as problematic, we have shown
      that nurses can be enabled to make changes to their practice that have a positive
      impact on both the mealtime experience and wider patient care.

PMID- 18047575
TI  - Parents' narratives about their experiences of their child's reconstructive
      genital surgeries for ambiguous genitalia.
AB  - AIM: The aim of this study was to initiate an exploration of parents'
      understanding and experiences of their child's reconstructive genital surgeries
      for ambiguous genitalia. BACKGROUND: The determination of gender for a child born
      with ambiguous genitalia is a complex medical and social process influenced by
      biological, psychological, social and cultural factors. Two main approaches
      exist; one promotes interventions (optimal gender policy) while the other
      suggests delaying interventions (informed consent policy) until the child can
      contribute to the decision. METHODS: An exploratory narrative inquiry design was
      chosen. Data were collected through narrative interviews with a purposive non
      random sample of 10 parents of eight children (aged 0-11 years) who had ambiguous
      genitalia. RESULTS: Parents' stories reflected strong protective instincts
      towards their children along with feelings of shock and disbelief. Parents'
      social construction of gender influenced their attitudes and beliefs about their
      child's ambiguous genitalia and the need for surgery. Parents' desired to be
      'good parents' and do what they perceived as 'right' for their child. They
      considered genital surgery as a necessity primarily relying on medical advice to
      guide them at times of uncertainty and confusion. Parents rarely shared stories
      about their child's surgeries/genitalia outside of the couple relationship and
      these stories were often referred to as 'secrets'. CONCLUSION: Having a child
      with ambiguous genitalia was perceived as problematic and brought about changes
      in roles, responsibilities, goals and social status as a parent beyond those
      usually associated with parenthood. RELEVANCE TO CLINICAL PRACTICE: These early
      findings help increase awareness of parents' experiences and of the problems and
      emotional challenges that parents face when their child is born with genital
      ambiguity.

PMID- 18047574
TI  - Collecting factors related to the haemolysis of blood specimens.
AB  - AIM: The purpose of the study is to explore the collecting factors for the
      haemolysis of the blood specimens in a regional hospital in South Taiwan.
      BACKGROUND: Blood collecting is one of the most common procedures used in
      hospital. However, it often faces the risk of haemolysis of blood specimens
      during laboratory testing and the specimens collected can be easily rejected by
      the laboratory. METHODS: This is a descriptive and cross-sectional study. The
      purposive samples were collected from the blood specimens of the hospitalized
      patients or the emergency-room patients by using structured observational
      checklists which included demographic characteristics, caring factors and
      material factors. A total of 274 blood specimens was collected. RESULTS:
      Specimens obtained from non-antecubital sites were 3.35 times at risk of
      haemolysis as many as those from antecubital sites (p = 0.001). Blood collected
      into tubes through steel needles were 3.7 times more at risk of haemolysis as
      that through syringes (after removing needles) (p = 0.002). Specimens delivered
      by ward assistants were 8.7 times more at risk for haemolysis as those by the
      laboratory staff (p < 0.01). CONCLUSIONS: These findings suggest that nurse
      supervisors establish a protocol related to preventing haemolysis. Future
      research should explore the effectiveness of this protocol to verify the
      relationship between different gauges of steel needles or catheters and
      haemolysis. RELEVANCE TO CLINICAL PRACTICE: Nurse educators are encouraged to
      include the factors affecting and preventing haemolysis into the in service
      education. Therefore, findings may assist healthcare professionals in minimizing
      the risk of haemolysis and improve the quality of care.

PMID- 18047576
TI  - Improving the patient's experience of a bone marrow biopsy - an RCT.
AB  - AIMS: To compare nitrous oxide 50%/oxygen 50% (N(2)O/O(2)- entonox) plus local
      anaesthetic (LA) with placebo (oxygen) plus LA in the management of pain
      experienced by patients undergoing a bone marrow biopsy. BACKGROUND: Bone marrow
      biopsies are a common procedure for many haematological conditions. Despite the
      use of a LA, pain during the procedure has frequently been reported by patients.
      Previous research in pain management of other invasive diagnostic procedures
      (e.g. sigmoidoscopy) has reported N(2)O/O(2) as an effective alternative to LA.
      DESIGN: Double-blind randomized controlled trial. METHODS: Forty-eight patients
      requiring a bone marrow biopsy were randomized to receive either N(2)O/O(2) or
      oxygen in addition to their LA. Participants were asked to complete a pain score
      and comment on their experience of the procedure. RESULTS: Although the overall
      pain scores were moderate, there was a wide range of scores. N(2)O/O(2) resulted
      in significantly less pain for men, but not for women. All patients who had had
      previous biopsies reported significantly more pain, regardless of the gas used.
      There were no significant adverse effects in either group. CONCLUSION: N(2)O/O(2)
      is a safe, effective, easy-to-use analgesic which merits further investigation in
      potentially painful diagnostic (and other) interventions. Relevance to clinical
      practice. Relief of pain is an important issue for nurses. Appropriate assessment
      of pain experience is a key issue. Nurses should reflect on their own area of
      practice and identify what is known about the effectiveness of pain management
      from their patient's perspective. Individual differences may be important, and
      careful instruction regarding appropriate administration of analgesic agents,
      such as N(2)O/O(2) may enhance their effectiveness.

PMID- 18047577
TI  - A systematic review of peer teaching and learning in clinical education.
AB  - AIMS AND OBJECTIVES: The purpose of this review is to provide a framework for
      peer teaching and learning in the clinical education of undergraduate health
      science students in clinical practice settings and make clear the positive and
      negative aspects of this teaching and learning strategy. BACKGROUND: The practice
      of using peers incidentally or purposefully in the clinical education of
      apprentice or undergraduate health science students is a well-established
      tradition and commonly practiced, but lacks definition in its implementation.
      METHOD: The author conducted a search of health science and educational
      electronic databases using the terms peer, clinical education and undergraduate.
      The set limitations were publications after 1980 (2005 inclusive), English
      language and research papers. Selection of studies occurred: based on
      participant, intervention, research method and learning outcomes, following a
      rigorous critical and quality appraisal with a purposefully developed tool. The
      results have been both tabled and collated in a narrative summary. RESULTS:
      Twelve articles met the inclusion criteria, representing five countries and four
      health science disciplines. This review reported mostly positive outcomes on the
      effectiveness of peer teaching and learning; it can increase student's confidence
      in clinical practice and improve learning in the psychomotor and cognitive
      domains. Negative aspects were also identified; these include poor student
      learning if personalities or learning styles are not compatible and students
      spending less individualized time with the clinical instructor. CONCLUSIONS: Peer
      teaching and learning is an effective educational intervention for health science
      students on clinical placements. Preclinical education of students congruent with
      the academic timetable increases student educational outcomes from peer teaching
      and learning. Strategies are required prior to clinical placement to accommodate
      incompatible students or poor student learning. RELEVANCE TO CLINICAL PRACTICE:
      The findings from this systematic review, although not statistically significant,
      do have pragmatic implications for clinical practice. It can increase clinical
      placement opportunities for undergraduate health students, assist clinical staff
      with workload pressures and increase clinician time with clients, while further
      developing students' knowledge, skills and attitudes.

PMID- 18047578
TI  - Discharge training and counselling increase self-care ability and reduce
      postdischarge problems in CABG patients.
AB  - AIMS AND OBJECTIVES: The aim of this study was to determine how discharge
      training and counselling provided to patients, who had undergone coronary artery
      bypass graft (CABG) surgery, had effects on patients' self-care ability and on
      the problems encountered after discharge. The objectives were to help patients
      develop self-care behaviour to deal more comfortably with the problems caused by
      the disease and, hopefully, to reduce the number of problems they may encounter.
      BACKGROUND: CABG surgery patients needing to manage various aspects of their self
      care at home often find these tasks very difficult to carry out effectively.
      Discharge training and counselling services help patients undergoing CABG to
      develop self-care behaviours. DESIGN: The study was prospective and quasi
      experimental. METHODS: The intervention and control groups consisted of 57
      patients who were given discharge training and counselling by a researcher and 52
      patients who were given routines by a nurse, respectively. The intervention group
      began receiving discharge training and counselling on the day of hospitalization.
      These were provided according to their individual knowledge needs and patients
      were given a booklet developed for training purposes. Data were collected by
      researcher using the Personal Information Form, the Self-Care Agency Scale.
      RESULTS: It was found that the intervention group had a higher mean self-care
      score than the control group and experienced fewer problems following discharge
      compared with patients in the control group. CONCLUSION: The discharge training
      and counselling services given to patients in the intervention group had a
      positive impact on the self-care ability of these patients and on alleviating the
      problems they encountered. RELEVANCE TO CLINICAL PRACTICE: As discharge training
      and counselling services had a positive impact on the self-care and alleviation
      of the problems that patients encounter after being discharged, we recommend
      application of these services and the usage of the training booklet for CABG
      patients.

PMID- 18047579
TI  - Intracellular levels and activity of PvdS, the major iron starvation sigma factor
      of Pseudomonas aeruginosa.
AB  - In Pseudomonas aeruginosa the iron starvation sigma factor PvdS directs the
      transcription of pyoverdine and virulence genes under iron limitation. PvdS
      activity is modulated by pyoverdine through the surface signalling cascade
      involving the FpvA receptor and the inner membrane-spanning sensor FpvR. To gain
      insight into the molecular mechanisms enabling PvdS to compete with the major
      sigma RpoD for RNA polymerase (RNAP) binding, we determined the intracellular
      levels of RNAP, RpoD and PvdS in P. aeruginosa PAO1, and the effect of pyoverdine
      signalling on PvdS activity. Under iron limitation, P. aeruginosa contains 2221
      and 933 molecules of RNAP and RpoD per cell respectively. PvdS attains 62% of
      RpoD levels. The high PvdS content is partly offset by retention of 30% of PvdS
      on the membrane, lowering the concentration of cytosolic PvdS to 45% of RpoD
      levels. RNAP purification from iron-starved P. aeruginosa cells demonstrated that
      PvdS-RNAP is poorly represented compared with RpoD-RNAP (1 and 27% of total RNAP
      respectively). Pyoverdine signalling does not affect the PvdS cellular content
      but facilitates PvdS release from the membrane, increasing its cytosolic
      concentration from 35% in both pvdF and fpvA signalling mutants to 70% in the
      wild type and 83% in the fpvR mutant.

PMID- 18047580
TI  - Incorporation of a polypeptide segment into the beta-domain pore during the
      assembly of a bacterial autotransporter.
AB  - Bacterial autotransporters consist of an N-terminal 'passenger domain' that is
      transported into the extracellular space by an unknown mechanism and a C-terminal
      'beta-domain' that forms a beta-barrel in the outer membrane. Recent studies have
      revealed that fully assembled autotransporters have an unusual architecture in
      which a small passenger domain segment traverses the pore formed by the beta
      domain. It is unclear, however, whether this configuration forms prior to
      passenger domain translocation or results from the translocation of the passenger
      domain through the beta-domain pore. By examining the accessibility of tobacco
      etch virus protease sites and single-cysteine residues in the passenger domain of
      the Escherichia coli O157:H7 autotransporter EspP at different stages of protein
      biogenesis, we identified a novel pre-translocation intermediate whose topology
      resembles that of the fully assembled protein. This intermediate was isolated in
      the periplasm in cell fractionation experiments. The data strongly suggest that
      the EspP beta-domain and an embedded polypeptide segment are integrated into the
      outer membrane as a single pre-formed unit. The data also provide indirect
      evidence that at least some outer membrane proteins acquire considerable tertiary
      structure prior to their membrane integration.

PMID- 18047582
TI  - A stepwise model for double-stranded RNA processing by ribonuclease III.
AB  - RNA interference is mediated by small interfering RNAs produced by members of the
      ribonuclease III (RNase III) family represented by bacterial RNase III and
      eukaryotic Rnt1p, Drosha and Dicer. For mechanistic studies, bacterial RNase III
      has been a valuable model system for the family. Previously, we have shown that
      RNase III uses two catalytic sites to create the 2-nucleotide (nt) 3' overhangs
      in its products. Here, we present three crystal structures of RNase III in
      complex with double-stranded RNA, demonstrating how Mg(2+) is essential for the
      formation of a catalytically competent protein-RNA complex, how the use of two
      Mg(2+) ions can drive the hydrolysis of each phosphodiester bond, and how
      conformational changes in both the substrate and the protein are critical
      elements for assembling the catalytic complex. Moreover, we have modelled a
      protein-substrate complex and a protein-reaction intermediate (transition state)
      complex on the basis of the crystal structures. Together, the crystal structures
      and the models suggest a stepwise mechanism for RNase III to execute the
      phosphoryl transfer reaction.

PMID- 18047581
TI  - Periplasmic phosphorylation of lipid A is linked to the synthesis of undecaprenyl
      phosphate.
AB  - One-third of the lipid A found in the Escherichia coli outer membrane contains an
      unsubstituted diphosphate unit at position 1 (lipid A 1-diphosphate). We now
      report an inner membrane enzyme, LpxT (YeiU), which specifically transfers a
      phosphate group to lipid A, forming the 1-diphosphate species. (32)P-labelled
      lipid A obtained from lpxT mutants do not produce lipid A 1-diphosphate. In vitro
      assays with Kdo(2)-[4'-(32)P]lipid A as the acceptor shows that LpxT uses
      undecaprenyl pyrophosphate as the substrate donor. Inhibition of lipid A 1
      diphosphate formation in wild-type bacteria was demonstrated by sequestering
      undecaprenyl pyrophosphate with the cyclic polypeptide antibiotic bacitracin,
      providing evidence that undecaprenyl pyrophosphate serves as the donor substrate
      within whole bacteria. LpxT-catalysed phosphorylation is dependent upon transport
      of lipid A across the inner membrane by MsbA, a lipid A flippase, indicating a
      periplasmic active site. In conclusion, we demonstrate a novel pathway in the
      periplasmic modification of lipid A that is directly linked to the synthesis of
      undecaprenyl phosphate, an essential carrier lipid required for the synthesis of
      various bacterial polymers, such as peptidoglycan.

PMID- 18047583
TI  - Sex- or gender-specific medicine in hepatology.
AB  - Sex- or gender-specific medicine is an up-to-date medical science in recent
      medical care. Medical doctors must offer better medical care and should
      understand and elucidate the mechanisms underlying the sex or gender differences
      regarding the incidence or etiology, clinical features, and natural history or
      response to therapies. Sex or gender differences are frequently seen among liver
      diseases, such as viral hepatitis, alcoholic liver disease, non-alcoholic fatty
      liver disease, autoimmune hepatitis, primary biliary cirrhosis, primary
      sclerosing cholangitis and hepatocellular carcinoma. The mechanisms of sex or
      gender differences, however, are still unclear. Clinicians and basic scientists
      are required to cooperatively contribute to the development of sex- or gender
      specific medicine to establish an accurate diagnosis and prophylaxis.

PMID- 18047584
TI  - Ultraviolet A induced modulation of gap junctional intercellular communication by
      P38 MAPK activation in human keratinocytes.
AB  - Aberrant gap junctional intercellular communication (GJIC) has been implicated in
      tumor development and progression. UltravioletA (UVA)-induced oxidative stress
      has been associated with skin carcinogenesis. We report a potential link between
      GJIC and the cellular stress response induced by UVA in normal human
      keratinocytes (NHK). In this study, UVA irradiation (10 J/cm(2)) compromised GJIC
      integrity in absence of cytotoxic effects as demonstrated by the absence of cell
      death and by the reversibility of GJIC down-regulation. Inhibition of
      communication by UVA was associated with hyperphosphorylation and decreased
      expression of connexin43 (Cx43), the most abundant gap junction protein expressed
      by keratinocytes. Cx43 hyperphosphorylation induced by UVA is, at least in part,
      mediated through mitogen-activated protein kinase (MAPK) activation as Ser279 and
      Ser282 sites, two downstream direct targets of p38 MAPK were found to be
      phosphorylated after UVA treatment. However, inhibition of p38 MAPK activity did
      not significantly protect from cell-cell communication inhibition because of a
      strong cellular cytotoxicity observed with SB202190 and SB203580, two selective
      inhibitors of p38 MAPK, in combination with UVA that compromises the outcome of
      dye transfer assay. By contrast, in Hacat cell line, inhibition of p38 activity
      reduced both phosphorylation and degradation of Cx43, demonstrating that these
      events are correlated.

PMID- 18047585
TI  - Voxel-based 3D MRI analysis helps to detect subtle forms of subcortical band
      heterotopia.
AB  - PURPOSE: To evaluate the potential diagnostic value of a novel magnetic resonance
      image (MRI) postprocessing technique in subtle forms of subcortical band
      heterotopia (SBH). The method was introduced to improve the visualization of
      blurred gray-white matter junctions associated with focal cortical dysplasia but
      was found to be applicable also to SBH. METHODS: In the voxel-based MRI analysis
      presented here, T1-weighted MRI volume data sets are normalized and segmented
      using standard algorithms of SPM5. The distribution of gray and white matter is
      analyzed on a voxelwise basis and compared with a normal database of 150
      controls. Based on this analysis, a three-dimensional feature map is created that
      highlights brain areas if their signal intensities fall within the range between
      normal gray and white matter and differ from the normal database in this respect.
      The method was applied to the MRI data of 378 patients with focal epilepsy in
      three different epilepsy centers. RESULTS: SBH was diagnosed in seven patients
      with five of them showing subtle forms of SBH that had gone unrecognized in
      conventional visual analysis of MRI and were only detected by MRI postprocessing.
      In contrast to distinct double cortex syndrome, these patients had partial double
      cortex with SBH mostly confined to posterior brain regions. CONCLUSIONS: The
      results of this study suggest that a considerable part of cases with SBH might
      remain unrecognized by conventional MRI. Voxel-based MRI analysis may help to
      identify subtle forms and appears to be a valuable additional diagnostic tool in
      the evaluation of patients with cryptogenic epilepsy.

PMID- 18047587
TI  - The unseen majority: soil microbes as drivers of plant diversity and productivity
      in terrestrial ecosystems.
AB  - Microbes are the unseen majority in soil and comprise a large portion of life's
      genetic diversity. Despite their abundance, the impact of soil microbes on
      ecosystem processes is still poorly understood. Here we explore the various roles
      that soil microbes play in terrestrial ecosystems with special emphasis on their
      contribution to plant productivity and diversity. Soil microbes are important
      regulators of plant productivity, especially in nutrient poor ecosystems where
      plant symbionts are responsible for the acquisition of limiting nutrients.
      Mycorrhizal fungi and nitrogen-fixing bacteria are responsible for c. 5-20%
      (grassland and savannah) to 80% (temperate and boreal forests) of all nitrogen,
      and up to 75% of phosphorus, that is acquired by plants annually. Free-living
      microbes also strongly regulate plant productivity, through the mineralization
      of, and competition for, nutrients that sustain plant productivity. Soil
      microbes, including microbial pathogens, are also important regulators of plant
      community dynamics and plant diversity, determining plant abundance and, in some
      cases, facilitating invasion by exotic plants. Conservative estimates suggest
      that c. 20 000 plant species are completely dependent on microbial symbionts for
      growth and survival pointing to the importance of soil microbes as regulators of
      plant species richness on Earth. Overall, this review shows that soil microbes
      must be considered as important drivers of plant diversity and productivity in
      terrestrial ecosystems.

PMID- 18047586
TI  - Linking traits of foraging animals to spatial patterns of plants: social and
      solitary ants generate opposing patterns of surviving seeds.
AB  - Foraging traits of seed predators are expected to impact the spatial structure of
      plant populations, community dynamics and diversity. Yet, many of the key
      mechanisms governing distance- or density-dependent seed predation are poorly
      understood. We designed an extensive set of field experiments to test how seed
      predation by two harvester ant species interact with seed dispersal in shaping
      the spatial patterns of surviving seeds. We show that the Janzen-Connell
      establishment pattern can be generated by central-place foragers even if their
      focal point is located away from the seed source. Furthermore, we found that
      differences in the social behaviour of seed predators influence their sensitivity
      to seed density gradients and yield opposing spatial patterns of surviving seeds.
      Our results support the predictions of a recent theoretical framework that
      unifies apparently opposing plant establishment patterns, and suggest that
      differences in foraging traits among seed predators can drive divergent pathways
      of plant community dynamics.

PMID- 18047588
TI  - Demographic analysis of continuous-time life-history models.
AB  - I present a computational approach to calculate the population growth rate, its
      sensitivity to life-history parameters and associated statistics like the stable
      population distribution and the reproductive value for exponentially growing
      populations, in which individual life history is described as a continuous
      development through time. The method is generally applicable to analyse
      population growth and performance for a wide range of individual life-history
      models, including cases in which the population consists of different types of
      individuals or in which the environment is fluctuating periodically. It
      complements comparable methods developed for discrete-time dynamics modelled with
      matrix or integral projection models. The basic idea behind the method is to use
      Lotka's integral equation for the population growth rate and compute the integral
      occurring in that equation by integrating an ordinary differential equation,
      analogous to recently derived methods to compute steady-states of physiologically
      structured population models. I illustrate application of the method using a
      number of published life-history models.

PMID- 18047589
TI  - Problems for people with epilepsy beyond seizures.

PMID- 18047590
TI  - Long-term social outcomes for children with epilepsy.
AB  - Children with epilepsy often grow into adults with significant social problems
      including decreased employment, marriage, social relationships, and independent
      living arrangements. These problems are noted in population-based longitudinal
      and cross-sectional studies from many countries. Learning disorder and mental
      handicap are the most consistent predictors of poor social outcome. Epilepsy
      variables, even remission, appear to have little effect. The influence of
      epilepsy on social outcome is greater than found in other childhood chronic
      disease control groups. More attention and research is needed to correct these
      unfortunate outcomes.

PMID- 18047591
TI  - Social stigma for adults and children with epilepsy.
AB  - For many people with epilepsy, the continuing social reality of their condition
      is as a stigma. Epilepsy stigma has three different levels; internalized,
      interpersonal, and institutional. While there have been documented improvements
      in public attitudes towards epilepsy, the remnants of "old" ideas about epilepsy
      continue to inform popular concepts resulting in a difficult social environment
      for those affected. The social and quality of life problems arising from a
      diagnosis of epilepsy can represent greater challenges than are warranted by its
      clinical severity. The relationship between stigma and impaired quality of life
      is well documented. Tackling the problem of stigma effectively requires that all
      three of different levels at which it operates are systematically addressed.

PMID- 18047592
TI  - An overview of epilepsy and driving.
AB  - Operating a motor vehicle is important to people with epilepsy (PWE). Being
      allowed to legally drive, largely depends on being seizure free for a defined
      period of time and being physically capable. Each patient's driving situation
      should be considered individually with advice offered guided by the goals of
      maximizing safety for both PWE and the public. There are considerable risks
      associated with driving for PWE or other medical conditions. Unfortunately, laws
      that govern driving are not uniform from state to state or country to country,
      requiring individual practitioners to be familiar with the local regulations.
      Good medical care leading to improved seizure control may allow PWE to drive and
      improve their quality of life. The privilege of driving a motor vehicle is
      important for many people with and without epilepsy. Many factors impact the
      ability to drive and laws governing driving and epilepsy are quite variable
      around the USA and the world. Being restricted from driving due to seizures
      represents a significant event in one's life affecting independence, sometimes
      employment and quality of life. The privilege of operating a motorized vehicle is
      granted by some form of governmental agency in virtually every state and country.

PMID- 18047593
TI  - The burden of normality: a framework for rehabilitation after epilepsy surgery.
AB  - This paper describes a conceptual framework that generates a modus operandi for
      rehabilitation after epilepsy surgery derived from regular longitudinal and
      prospective follow-up of patients and families. The framework focuses on patient
      experiences of undergoing surgery placed within the context of the family and
      broader community. It adopts a holistic view of patient care to understand the
      complex interactions between neurobiological and psychosocial factors that
      determine surgical outcome in the eyes of the patient, family, and clinical team.
      It emphasises the importance of anticipating postoperative adjustment issues
      using a preventive treatment approach.

PMID- 18047594
TI  - Psychosis in epilepsy patients.
AB  - Epileptic psychoses reflect a fundamental disruption in the fidelity of mind and
      occur during seizure freedom or during or after seizures. The psychotic symptoms
      in epilepsy share some qualities with schizophrenic psychosis, such as positive
      symptoms of paranoid delusions and hallucinations. Psychotic syndromes in
      epilepsy are most common but not exclusively associated with temporal lobe
      epilepsy. De Novo psychosis following epilepsy surgery is rare. Forced
      normalization-psychosis associated with dramatic reduction of epileptiform
      activity or seizures is described in small series only. Ictal and postictal
      psychosis can be prevented with seizure control, but postictal and chronic
      interictal psychoses require multidisciplinary and psychopharmacologic
      management.

PMID- 18047595
TI  - Epilepsy and mood disorders.
AB  - Mood disorders (MD) are a frequent comorbidity of epilepsy with a negative impact
      on quality of life. The higher prevalence of MD in people with epilepsy (PWE) is
      most likely a reflection of a bidirectional relation between the two conditions,
      and common pathogenic mechanisms. Treatment of MD in PWE is safe with selective
      serotonin reuptake inhibitor (SSRIs) and serotonin-norepinephrine reuptake
      inhibitors (SNRIs), but nonpsychiatrists need to know when to refer these
      patients to a psychiatrist for further evaluation and treatment.

PMID- 18047596
TI  - The basic science of memory as it applies to epilepsy.
AB  - The mechanisms of memory delineated by the model of long-term potentiation (LTP)
      are similar to those underlying epileptogenesis by kindling. Memory is impaired
      by seizures and epilepsy. High frequency neural activity is important in both
      memory formation and seizures. Both kindling and LTP are most effectively induced
      by high-frequency stimuli, involve synaptic facilitation, and share overlapping
      molecular mechanisms, such as N-methyl-d-aspartate (NMDA) receptor-induced
      calcium cascade and protein synthesis. The hippocampus contributes to both
      through its role in memory formation and its low seizure threshold.

PMID- 18047597
TI  - Long-term memory impairment in patients with focal epilepsy.
AB  - In temporal lobe epilepsy, long-term memory disturbance starts early in life
      mainly affecting declarative memory. Primary impairment of episodic memory often
      results in reduced semantic and autobiographic memory. Neuropsychological
      performance predicts academic achievement and everyday life functioning while
      subjective memory complaints are highly correlated with depression. Memory
      impairment is also influenced by initial brain damage, developmental retardation
      and dynamic factors (e.g., seizure frequency, medication). Damage of functional
      tissue, low mental reserve capacity, and poor seizure outcome increase the risk
      for postsurgical memory impairment whereas functional release due to seizure
      freedom counteracts negative impact. Preliminary findings indicate that
      postsurgical training improves memory deficits and encourage further research.

PMID- 18047599
TI  - The autism-epilepsy connection.
AB  - The high prevalence of epilepsy in children with autism supports a neurobiologic
      etiology for autism. It remains unclear whether seizures and epileptiform
      activity on the EEG are causative or comorbid. It is also uncertain if focal
      epileptiform EEG abnormalities may be associated with stable cognitive
      impairment. Even less clear is whether these EEG abnormalities can result in the
      combination of language and social dysfunction seen in autistic spectrum
      disorders.

PMID- 18047598
TI  - Genetically seizure-prone or seizure-resistant phenotypes and their associated
      behavioral comorbidities.
AB  - It was questioned whether amygdala kindling, a model of temporal lobe epilepsy,
      is under genetic control, and is associated with comorbid behavioral features.
      Initially, rats were selectively bred for speed of amygdala kindling, and, in
      subsequent generations, were assessed in behavioral paradigms to measure
      activity, emotionality, impulsivity, and learning. Clearly kindling was under
      genetic control, as two strains were developed to be either Fast or Slow to
      kindle, and each was associated with different neurological, electrophysiological
      and behavioral features. Behaviorally, the Fast rats appear much like humans with
      attention deficit hyperactivity disorder (ADHD), showing easy distraction,
      hyperactivity and impulsivity, compared to Slow rats.

PMID- 18047600
TI  - The interaction between sleep and epilepsy.
AB  - Sleep and epilepsy are interrelated. Understanding the relationship between
      epilepsy and sleep is important for optimizing management of the epilepsy patient
      in several ways. First, sleep modulates the expression of epileptic seizures and
      interictal epileptiform discharges. Second, epilepsy and its treatment influence
      sleep organization and daytime alertness, and may contribute to, or ameliorate,
      sleep disorders. Finally, treatment of a coexisting sleep disorder may improve
      seizure control, daytime alertness, and health-related quality of life. In this
      article, aspects related to the interrelationship of sleep and epilepsy will be
      discussed and the model of how sleep can interact with a neurological disorder
      will be illustrated.

PMID- 18047601
TI  - Screening for bone health in epilepsy.
AB  - Elderly and young patients with epilepsy are at risk for fractures from seizure
      and antiepileptic drug (AED) related falls and from epilepsy and AED related
      lowered bone mass. Enzyme inducing AEDs are often implicated, although, nonenzyme
      inducing medications may also impact epilepsy bone disease. Screening for bone
      health with direct measures, such as bone densitometry by dual-energy x-ray
      absorptiometry (DEXA) and indirectly via biochemical markers of bone turnover may
      help identify patients who are at increased risk for fractures and offer an
      opportunity for intervention.

PMID- 18047602
TI  - Weight issues for people with epilepsy--a review.
AB  - Weight gain or loss is not an integral part of epilepsy although a sedentary
      lifestyle can contribute to weight gain. Pharmacological treatment for epilepsy
      may be associated with substantial weight changes that may increase morbidity and
      impair adherence to the treatment regimen. Antiepileptic drugs (AEDs) associated
      with weight loss are felbamate, topiramate, and zonisamide. AEDs associated with
      weight gain are gabapentin, pregabalin, valproic acid, and vigabatrin and
      possibly, carbamazepine. Weight neutral AEDs are lamotrigine, levetiracetam, and
      phenytoin. In clinical practice it is critical to weigh patients regularly and
      AED selection should be based on each patient's profile without sacrificing
      therapeutic efficacy.

PMID- 18047603
TI  - Defining safety tolerance limits.

PMID- 18047604
TI  - Definition of the tear trough and the tear trough rating scale.
AB  - BACKGROUND: Nasojugal groove and tear trough are interchangeably used terms by
      many authors in the literature despite the fact that they describe distinct and
      different anatomic entities. In the same vein, there are multiple descriptions of
      treatments and techniques for the cosmetic improvement of these anatomic areas
      without specifically addressing the anatomic difference between them. OBJECTIVE:
      This study aims to define the anatomic characteristics of the tear trough and
      describe a novel classification scale for the evaluation of the tear trough
      deformity. METHODS: The tear trough rating scale (TTRS) was applied to a
      representative sample of our patient population. Five of the authors evaluated
      each patient using the TTRS, and the numeric results were tabulated and compared.
      Results The TTRS provided an effective, reproducible method for evaluating tear
      trough deformities, and there was very little interobserver variability.
      CONCLUSION: The tear trough should be defined as the depression of the medial
      lower eyelid just lateral to the anterior lacrimal crest and limited in its
      inferior aspect by the inferior orbital rim. The TTRS is a reliable tool for the
      classification of the tear trough and evaluation of therapeutic and cosmetic
      interventions.

PMID- 18047605
TI  - Applications of microemulsions in cosmetics.
AB  - Since microemulsions were discovered approximately six decades ago, their
      applications in several fields, including cosmetics, have been increased due to
      their good appearance, thermodynamic stability, high solubilization power, and
      ease of preparation. In addition, microemulsions can enhance skin permeation of
      the loaded substances. They are classified into three types: oil-in-water,
      bicontinuous, and water-in-oil. All types of microemulsions can be formed
      spontaneously when the ratios of oil, water, and amphiphile in the systems are
      appropriate. These proper ratios can be found in a microemulsion region of a
      phase diagram. The efficiency of microemulsions in topical application is related
      to microemulsion type. Microemulsion characterization needs a combination of the
      data from several experimental techniques. Numerous applications of cosmetic
      microemulsions include skin-care, hair-care, and personal-care products for
      improving the product efficiency and stability. Moreover, new materials have been
      developed to be used in cosmetic microemulsion formulations for increasing the
      product efficiency and reducing the toxicity. The aim of this review is to
      present some basic information of microemulsions and novel applications of
      microemulsions in cosmetic formulations.

PMID- 18047606
TI  - Granulomatous reactions to permanent cosmetic tattoos successfully treated with
      topical steroids and allopurinol.
AB  - Two female patients presented nodular erythematous lesions overlying a permanent
      tattooed eyebrow and lip, respectively. Histologic examination showed in both
      cases epithelioid granulomas in close relation with scattered pigment.
      Complementary examinations and follow-up disclosed a sarcoidosis. The lesions
      resolved after treatment with topical steroids and also oral allopurinol in one
      of the cases. Allopurinol may be an effective treatment for granulomatous
      reactions to foreign body particles.

PMID- 18047607
TI  - Genomic expression changes induced by topical N-acetyl glucosamine in skin
      equivalent cultures in vitro.
AB  - N-acetyl glucosamine (NAG) has been shown to be effective in reducing the
      appearance of hyperpigmented spots. From published in vitro mechanistic testing,
      glucosamine inhibits enzymatic glycosylation, a required processing step in
      converting inactive human pro-tyrosinase to the active tyrosinase, a key enzyme
      in the production of melanin. There is also published literature discussing the
      anti-inflammatory and antioxidant properties of glucosamine compounds. To
      identify additional mechanisms by which NAG might affect melanin production, an
      in vitro genomics experiment was conducted in SkinEthic skin equivalent cultures,
      which were topically dosed with NAG vs. a vehicle control. Relative to vehicle,
      NAG reduced melanin production, and the expression of several pigmentation
      relevant genes were affected (down-regulated or up-regulated) by NAG treatment.
      Thus, there are several mechanisms that may be operative in the observed
      pigmentation effects.

PMID- 18047608
TI  - New cosmetic emulsions for dry skin.
AB  - The aim of this study was to formulate stable water-in-oil (w/o) emulsions
      containing oils with a high percentage of fatty acids, sterols, vitamins,
      cholesterol, and ceramides in order to improve topical treatment of dry skin
      conditions. Two w/o emulsions were developed and physicochemical characterized.
      The biological effects of the formulations were assessed on the volar surface of
      the human foreharm over 28 days. The results obtained showed that areas treated
      by either cream were significantly different from the control area, as assessed
      by epidermal capacitance and sebometry over the 28 days. Treatment with cream
      containing ceramides presented higher values of sebometry and corneometry.
      According to the sensory evaluation performed, both creams were found to have
      good acceptability.

PMID- 18047609
TI  - The clinical anti-aging effects of topical kinetin and niacinamide in Asians: a
      randomized, double-blind, placebo-controlled, split-face comparative trial.
AB  - BACKGROUND: Kinetin and niacinamide are used in the cosmetic industry as anti
      aging agents. Neither the interactive/additive effects of these compounds nor the
      anti-aging efficacy on Asian skin has been studied. Objective To assess the
      clinical anti-aging effects and efficacy differences between kinetin plus
      niacinamide and niacinamide alone vs. vehicle placebo in an Asian cohort.
      METHODS: Fifty-two Taiwanese subjects were enrolled in a randomized, double
      blind, placebo-controlled, split-face comparative study. Group 1 subjects were
      treated with kinetin 0.03% plus niacinamide 4%, whereas group 2 subjects received
      niacinamide 4%. The treatment formulation was applied on one side of the face,
      whereas a placebo was applied on the other for a period of 12 weeks. We used
      noninvasive biometrological instruments to evaluate a variety of skin parameters
      at baseline and at weeks 4, 8, and 12. RESULTS: Persistent and significant
      reductions in spot, pore, wrinkle, and evenness counts were found at weeks 8 and
      12 in group 1. A significant increase in corneal hydration status was also
      evident at week 12, whereas persistent decreases in erythema index were apparent
      at 8 and 12 weeks. In group 2, significant reductions in pore and evenness counts
      at week 8 and wrinkle counts at week 12 were noted. CONCLUSION: We found kinetin
      and niacinamide exert a synergistic anti-aging effect. Our data suggest that
      these compounds have multiactive, multifunctional, and pluripotent effects on
      skin. They are also both promising to be included in the cutaneous anti-aging
      cosmeceuticals in the future.

PMID- 18047610
TI  - Submental fat reduction by mesotherapy using phosphatidylcholine alone vs.
      phosphatidylcholine and organic silicium: a pilot study.
AB  - BACKGROUND: Excess skin and fatty tissues beneath the jaw lead to a double chin
      deformity. Localized fat deposits in this area are a cause of discomfort and
      anguish, leading patients to undergo surgical procedures such as liposuction and
      dermolipectomy to improve the cosmetic effect. Both procedures require anesthesia
      and an operating room setting and are quite expensive. Fearful of extensive
      surgery and its complications, patients and physicians seek less invasive
      methods. Mesotherapy with phosphatidylcholine and other cocktails have been used
      to treat localized fat deposits. However, there are few published articles
      regarding its effectiveness and some are even anecdotal. OBJECTIVE: This study
      aims to determine the efficacy of phosphatidylcholine alone vs.
      phosphatidylcholine and organic silicium in submental fat reduction. METHODS:
      Twelve patients with submental fat deposit with no coexisting morbidity and with
      informed consent were included in the study. They were submitted to one to five
      treatment sessions with an average interval of 2 weeks between each session. The
      medication administered was injected, either pure phosphatidylcholine or a
      combination of phosphatidylcholine and organic silicium. Baseline measurements of
      submental fat using vernier caliper and digital photographs of the patients were
      taken during each treatment session. The occurrence of adverse effects was
      likewise noted. Results Among the 12 patients, 11 completed the treatment course,
      and 1 was excluded from the study because of failure to follow up. Both
      phosphatidylcholine and a combination of phosphatidylcholine and organic silicium
      were equally effective in reducing submental fat deposits. There was no
      significant difference as to the rate and degree of reduction. Significant
      reduction in the thickness of submental fat was achieved after three treatment
      sessions. Adverse reactions in both groups were mild and transitory ranging from
      heavy sensation, localized heat, nodulations, and slight bruising that abated 3
      to 5 days after treatment. Limitations As of this writing, information on the use
      of both phosphatidylcholine and organic silicium for mesotherapy of localized fat
      such as the submental area is scarce. The exact mechanisms of action of both
      treatments are likewise unknown. Ultrasound and histopathological changes were
      not documented. The study did not involve a double-blind, placebo-controlled
      design, and the sample size was small. CONCLUSION: Mesotherapy using
      phosphatidylcholine vs. phosphatidylcholine plus organic silicium was similarly
      effective in reducing submental fat. There was no significant difference between
      them in terms of rate and degree of reduction. Optimal reduction of submental fat
      was achieved after three treatment sessions. Adverse reactions were few, mild,
      and transitory. Therefore, both regimens are safe, efficacious, cost-effective,
      and can be used as alternatives to invasive surgical procedures.

PMID- 18047611
TI  - Role of liquid nitrogen alone compared with combination of liquid nitrogen and
      intralesional triamcinolone acetonide in treatment of small keloids.
AB  - Keloids are well-defined fibrous tissue overgrowths extending beyond the original
      defects. The purpose of our study was to compare the efficacy of liquid nitrogen
      cryosurgery alone with liquid nitrogen cryosurgery and intralesional
      triamcinolone acetonide combination. Study on 60 clinically diagnosed lesions of
      keloids from 21 patients was conducted to compare the efficacy of liquid nitrogen
      cryosurgery alone. The statistical analysis shows synergistic action of
      cryosurgery and corticosteroids may offer promise in the treatment.

PMID- 18047612
TI  - Marginal traction alopecia severity score: development and test of reliability.
AB  - BACKGROUND: Traction alopecia (TA) is common in African females. Although
      hairstyles are thought to be causal, the contribution of individual hairstyling
      variables to TA severity has not been quantified. The aim of the current study
      was to develop a severity scoring system (M-TAS score) for marginal TA, the
      commonest form of this disorder, and to test its reliability. METHOD: The margins
      of the scalp were divided into anterior and posterior with an imaginary line
      joining the tips of both ears. The anterior and posterior hairlines were further
      divided into three using the temporalis muscles and mastoid processes at the
      hairline as landmarks, respectively. Each examiner assessed each of the six
      areas. If any were found to have TA, the severity was scored using an examiner
      assessed system (tested once) or a picture matched score (tested twice). Ten and
      eight female patients with TA of varying severity were assessed by 11 and 9
      examiners (dermatologists, dermatology trainees, and nurses), respectively.
      RESULTS: The intraclass correlation coefficient (ICC) for interobserver agreement
      was larger with photograph-matched scores than with examiner estimated scores
      reaching substantial (0.61-0.80) and excellent (0.81-100) agreement for both
      anterior and posterior scores irrespective of level of skill of examiner. The ICC
      for intraobserver agreement with the photograph matched scores was 0.99.
      LIMITATIONS: The diagnosis of normal margin was excellent for the anterior yet
      poor for the posterior margin with photograph scores. The M-TAS score is not for
      diagnosis but to assess severity. CONCLUSION: The photograph-based M-TAS score
      requires validation with larger samples but could be a useful research tool for
      elucidating disease prevalence and determinants of TA as well for monitoring
      response to treatment.

PMID- 18047613
TI  - Pyogenic granuloma following treatment of a port-wine stain with intense pulsed
      ligt.

PMID- 18047614
TI  - An efficient method of preparing dressing materials for laser procedures.
AB  - Cutting numerous dressing materials for every laser-treated site is tedious and
      time-consuming. Here, we describe an efficient method of rapidly mass producing
      dressing materials. We found that a one-hole punch - commonly used in daily
      office work - can be used as a powerful tool for this laborious task.

PMID- 18047616
TI  - Threading warts: a beauty parlor dermatosis.
AB  - Threading is a common beauty parlor procedure usually performed to shape the
      eyebrows and remove unwanted facial hair for cosmetic reasons. Appearance of
      warts at the site of threading is an unusual phenomenon. We report two such
      cases, first as koebnerization from the initial lesion elsewhere on the patient's
      body and second, possibly from the infected material at the beauty parlor. We
      emphasize the importance of identification of this condition and discuss its
      dermatological and cosmetological perspectives.

PMID- 18047617
TI  - LVMH Recherche Symposium VII. Stem cells and skin: present and future. Abstracts.

PMID- 18047619
TI  - Water channels in chondrocyte function: another 'unexpected' role of aquaporins.

PMID- 18047620
TI  - Endothelins and NADPH oxidases in the cardiovascular system.
AB  - 1. The endothelin (ET) system and NADPH oxidase play important roles in the
      regulation of cardiovascular function, as well as in the pathogenesis of
      hypertension and other cardiovascular diseases. 2. Endothelins activate NADPH
      oxidases and thereby increase superoxide production, resulting in oxidative
      stress and cardiovascular dysfunction. Thus, NADPH oxidases may mediate the role
      of endothelins in some cardiovascular diseases. However, the role of reactive
      oxygen species (ROS) in mediating ET-induced vasoconstriction and cardiovascular
      disease remains under debate, as evidenced by conflicting reports from different
      research teams. Conversely, activation of NADPH oxidase can stimulate ET
      secretion via ROS generation, which further enhances the cardiovascular effects
      of NADPH oxidase. However, little is known about how ROS activate the endothelin
      system. It seems that the relationship between ET-1 and ROS may vary with
      cardiovascular disorders. 3. Endothelins activate NADPH oxidase via the ET
      receptor-proline-rich tyrosine kinase-2 (Pyk2)-Rac1 pathway. Rac1 is an important
      regulator of NADPH oxidase. There is ample evidence supporting direct stimulation
      by Rac1 of NADPH oxidase activity. In addition, Rac1-induced cardiomyocyte
      hypertrophy is mediated by the generation of ROS.

PMID- 18047621
TI  - Renal functional responses to ischaemia-reperfusion injury in normotensive and
      hypertensive rats following non-selective and selective cyclo-oxygenase
      inhibition with nitric oxide donation.
AB  - 1. Acute renal failure develops as a result of periods of renal ischaemia during
      cardiovascular surgery or hypovolaemic shock. The present study investigated the
      importance of endogenous prostaglandin production and nitric oxide (NO) in the
      renal haemodynamic and excretory responses to ischaemia-reperfusion both normally
      and in the hypertensive state by chronic administration of cyclo-oxygenase (COX)
      inhibitors. 2. Male Wistar and stroke-prone spontaneously hypertensive rats
      (SHRSP) were subjected to 30 min renal ischaemia and 2 h reperfusion following 7
      day treatment with vehicle, aspirin, NO-aspirin or celecoxib. 3. Renal blood flow
      was higher in the SHRSP treatment groups. Renal ischaemia increased blood
      pressure in all Wistar groups except that given aspirin, had no effect in the
      SHRSP and did not change renal blood flow in any group. Glomerular filtration
      rate was reduced throughout the reperfusion period in both rat strains. The
      postischaemic diuresis in the Wistar was enhanced by COX-2 inhibition, but not by
      aspirin or NO-aspirin. Urine flow increased in SHRSP during the postischaemic
      period, which was blunted by aspirin and NO-aspirin, but not by celecoxib. There
      was a postischaemic increase in fractional sodium excretion, the magnitude of
      which was unaltered by any drug in the Wistar rats, but was blunted by aspirin,
      NO-aspirin and celecoxib in SHRSP. 4. These results suggest that products of COX
      activity contribute to the renal responses to ischaemia-reperfusion injury, but
      in different ways, in SHRSP, which may reflect variations in renal prostaglandin
      and NO production in the hypertensive state.

PMID- 18047622
TI  - Effects of direct haemoperfusion through fibres immobilizing polymyxin B and
      nafamostat mesilate on endotoxaemia in conscious Guinea-pigs.
AB  - 1. Direct haemoperfusion through a network of fibres immobilizing polymyxin B
      (PMX-B) is used for the treatment of septic shock, but the mechanism underlying
      its clinical benefits remains unclear. The aims of the present study were to
      assess the actions of direct haemoperfusion through fibres immobilizing PMX-B
      (PMX-DHP) on the effects of exogenously administered endotoxin in conscious
      guinea-pigs and to examine the difference in the effects of heparin compared with
      nafamostat mesilate (NM) used as an anticoagulant. Although nafamostat is widely
      used in Japan, the agent cannot necessarily be used elsewhere in the world.
      Therefore, the study aimed to investigate and elucidate the effectiveness of NM
      compared with heparin. 2. Colonic motion was monitored continuously via telemetry
      using a force transducer attached to the taenia caecum, whereas blood pressure
      was monitored using a carotid artery catheter. To establish a haemoperfusion
      circuit in each freely moving and conscious guinea-pig, catheters were implanted
      in the carotid artery and the jugular vein, tunnelled subcutaneously,
      exteriorized at the back of the neck in contact with a lightweight tethering
      spring and attached to a swivel device at the top of the cage. On the day after
      the operation, lipopolysaccharide (LPS; Escherichia coli, O111:B4; 1 mg/kg) was
      administered i.v. and PMX-DHP was conducted for 2 h. Heparin (50 IU/h) or NM (0.4
      mg/h) was used as the anticoagulant. Furthermore, guinea-pigs were administered a
      lethal dose of LPS (10 mg/kg) and the survival rate was examined for animals
      undergoing PMX-DHP compared with control animals. 3. In guinea-pigs treated with
      PMX-DHP, relaxation of colonic longitudinal muscle caused by LPS was
      significantly suppressed, as were decreases in blood pressure. Of the two
      anticoagulants used, NM was more effective than heparin. In addition, PMX-DHP
      significantly increased the survival rate of guinea-pigs that received
      potentially lethal doses of LPS. 4. In conscious and unrestrained guinea-pig
      endotoxaemia model, PMX-DHP significantly improved intestinal paralysis and
      decreases in blood pressure. These effects were augmented more by NM than by
      heparin when an anticoagulant was used in the perfusion process. These findings
      suggest that haemoperfusion using PMX and NM performed in the early stage of
      endotoxaemia is an effective treatment.

PMID- 18047623
TI  - Effects of Yunke (technetium-99 conjugated with methylene diphosphonate; (99)Tc
      MDP) and/or colloidal chromic phosphate phosphonium-32, alone and in combination,
      in rats with adjuvant arthritis.
AB  - 1. The present study investigated the therapeutic effects of both single and
      combination treatment with Yunke (technetium-99 conjugated with methylene
      diphosphonate; (99)Tc-MDP) and colloidal chromic phosphate (32)P (phosphonium-32)
      in rats with adjuvant arthritis (AA). 2. Rats were randomly allocated to one of
      five groups: (i) normal control group (sham operated and treated with normal
      saline); (ii) AA control group (arthritis induced with adjuvant and treated with
      normal saline); (iii) (32)P colloid group (arthritis induced with adjuvant and
      treated with a single intra-articular injection of colloidal chromic phosphate
      phosphonium-32 (0.02 mCi) and i.p. injections of normal saline every other day);
      (iv) Yunke group (arthritis induced with adjuvant and treated with i.p. Yunke
      (2.5 x 10(-3) microg/kg) every other day and single intra-articular injection of
      normal saline); and (v) combination group (arthritis induced with adjuvant and
      treated with a combination of both therapies). 3. The left-to-right diameter
      (LRD) of the left hind ankle, serum levels of tumour necrosis factor (TNF) and
      interleukin (IL)-1b and histological sections of the ankle joints were examined
      at different time points. 4. The LRD of the left hind ankle was smaller for the
      combination group compared with (32)P colloid alone at Week 4 (7.11 +/- 0.28 vs
      7.57 +/- 0.24 mm, respectively; P < 0.001). The combination treatment was more
      effective than (32)P colloid alone in decreasing serum TNF (1.614 +/- 0.368 vs
      1.977 +/- 0.255 ng/mL, respectively; P = 0.002 for Week 4) and IL-1b (0.271 +/-
      0.027 vs 0.308 +/- 0.020 ng/mL, respectively for Week 4; 0.209 +/- 0.023 vs 0.255
      +/- 0.016 ng/mL, respectively for Week 6; both P = 0.001). Histologically, the
      combination group exhibited less synovium proliferation compared with Yunke
      treatment alone and decreased inflammatory cell infiltration compared with (32)P
      colloid alone. 5. In conclusion, the combination of Yunke and (32)P colloid is
      more effective in the treatment of AA in rats compared with Yunke or (32)P
      colloid alone.

PMID- 18047624
TI  - Effects of dipeptidyl peptidase iv inhibition on arterial blood pressure.
AB  - 1. The aim of the present study was to determine whether inhibition of dipeptidyl
      peptidase IV (DPP IV) elevates arterial blood pressure and whether any such
      effect is dependent on genetic background, the sympathetic nervous system and
      Y(1) receptors. The rationale behind this study was that: (i) neuropeptide (NP)
      Y(1-36) and peptide YY(1-36) (PYY(1-36)) are endogenous Y(1) receptor agonists
      and are metabolised by DPP IV to NPY(3-36) and PYY(3-36), which are not Y(1) but
      rather selective Y(2) receptor agonists; (ii) Y(1) receptors mediate
      vasoconstriction, whereas Y(2) receptors have little effect on vascular tone;
      (iii) vaso-constrictor effect of the Y(1) receptor is enhanced in spontaneously
      hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats; and
      (iv) NPY(1-36) is released from sympathetic nerve terminals. 2. We examined the
      effects of acute administration of 3-N-[(2S,3S)-2-amino-3-methylpentanoyl]-1,3
      thiazolidine (P32/98; a DPP IV inhibitor) on arterial blood pressure in
      anaesthetized adult SHR and WKY rats in the absence and presence of either
      captopril, hydralazine or chlorisondamine to lower basal mean arterial blood
      pressure (MABP) by different mechanisms (inhibition of angiotensin-converting
      enzyme, direct vasodilation and ganglionic blockade, respectively). 3. In naive
      SHR with severely elevated basal blood pressures (MABP = 176 +/- 3 mmHg; n = 4),
      i.v. boluses (1, 3 and 10 mg/kg) of P32/98 did not affect blood pressure. 4. When
      basal blood pressure was reduced by pretreatment of SHR with either captopril (30
      mg/kg, i.v.; MABP = 116 +/- 3 mmHg; n = 9) or hydralazine (5 mg/kg, i.p.; MABP =
      84 +/- 3 mmHg; n = 7), P32/98 (1, 3 and 10 mg/kg) caused significant dose-related
      increases in arterial blood pressure (4 +/- 2, 10 +/- 2 and 12 +/- 3 mmHg in the
      captopril-pretreated group, respectively (P < 0.01); 5 +/- 2, 8 +/- 3 and 11 +/-
      4 mmHg in the hydralazine-pretreated group, respectively (P < 0.01)). 5. The
      increases in arterial blood pressure induced by P32/98 in captopril- or
      hydralazine-pretreated SHR were entirely blocked by pretreatment with the
      selective Y(1) receptor antagonist N2-(diphenylacetyl)-N-[(4
      hydroxyphenyl)methyl]-d-arginine amide (BIBP 3226; 6 mg/kg per h). 6. When basal
      blood pressure was reduced in SHR by pretreatment with chlorisondamine (10 mg/kg,
      s.c.; MABP = 108 +/- 4 mmHg; n = 7), inhibition of DPP IV with P32/98 did not
      affect arterial blood pressure. Basal heart rate in chlorisondamine-treated SHR
      was significantly reduced compared with naive SHR, captopril-pretreated SHR and
      hydralazine-pretreated SHR, indicating effectiveness of ganglionic blockade. 7.
      Unlike the results in genetically hypertensive animals, in normotensive WKY rats
      pretreated with captopril (30 mg/kg, i.v.; MABP = 81 +/- 4 mmHg; n = 6), or
      hydralazine (5 mg/kg, i.p.; MABP = 63 +/- 4 mmHg; n = 4) or chlorisondamine (10
      mg/kg, s.c.; MABP = 63 +/- 4 mmHg; n = 5), P32/98 did not affect arterial blood
      pressure. 8. We conclude that, in genetically susceptible animals, inhibition of
      DPP IV increases arterial blood pressure via Y(1) receptors when elevated blood
      pressure is reduced with antihypertensive drugs provided that the sympathetic
      nervous system is functional. The results suggest vigilance because DPP IV
      inhibitors are used more widely in hypertensive patients treated with
      antihypertensive drugs.

PMID- 18047625
TI  - Oral mitemcinal (GM-611), an erythromycin-derived prokinetic, accelerates normal
      and experimentally delayed gastric emptying in conscious dogs.
AB  - 1. We examined effects of orally administered mitemcinal, an erythromycin-derived
      motilin agonist, on gastric emptying and antroduodenal motility in conscious
      normal dogs and conscious dogs with experimentally delayed gastric emptying. For
      comparison, we also examined the effects of orally administered cisapride. 2.
      Gastric emptying was assessed by adding paracetamol to the test meal and
      determining three of its pharmacokinetic parameters as indices of gastric
      emptying. Antroduodenal motility was assessed from the output of force
      transducers chronically implanted in the gastric antrum and duodenum. 3. In
      normal dogs, mitemcinal (0.25, 0.5 and 1 mg/kg) dose-dependently accelerated
      gastric emptying, significantly increasing all three indices at doses of 0.5 and
      1 mg/kg; cisapride (1, 3 and 10 mg/kg) had no significant effect. Mitemcinal also
      dose-dependently stimulated antroduodenal motility in the interdigestive and
      digestive states. Cisapride, at 100-fold the dose, produced similar effects in
      the interdigestive state, but mixed results in the digestive state. 4. In dogs
      with delayed gastric emptying induced by subcutaneous clonidine (0.03 mg/kg),
      mitemcinal (0.25, 0.5 and 1 mg/kg) dose-dependently improved delayed gastric
      emptying, significantly increasing two of three indices at a dose of 1 mg/kg.
      Cisapride (1, 3 and 10 mg/kg) caused non-significant increases in the indices of
      gastric emptying, with roughly bell-shaped dose-response curves. The highest dose
      of mitemcinal (1 mg/kg) also stimulated antroduodenal motility. 5. In dogs with
      delayed gastric emptying induced by vagotomy, mitemcinal (0.125, 0.25 and 0.5
      mg/kg) dose-dependently improved delayed gastric emptying, significantly
      increasing all three indices at doses of 0.25 and 0.5 mg/kg. Cisapride (3 mg/kg)
      restored the indices to roughly prevagotomy levels, but none of the increases was
      significant. Mitemcinal, at a dose of 0.25 mg/kg, also stimulated antroduodenal
      motility. 6. Because delayed gastric emptying is the basic characteristic of
      gastroparesis, the fact that mitemcinal accelerated gastric emptying in dogs with
      normal and delayed gastric emptying much more robustly than cisapride adds to the
      evidence that mitemcinal is likely to be useful for the treatment of patients
      with gastroparesis.

PMID- 18047626
TI  - Effect of polyphenol-containing azuki bean (Vigna angularis) extract on blood
      pressure elevation and macrophage infiltration in the heart and kidney of
      spontaneously hypertensive rats.
AB  - 1. Hypertension is a major risk factor for myocardial infarction and renal
      damage, and it has also been shown to have pro-inflammatory actions that increase
      the formation of reactive oxygen species. Macrophage infiltration has been
      suggested to play a role in the pathogenesis of hypertension. Azuki beans are
      known to contain pro-anthocyanidins, a group of polyphenolic bioflavonoids with
      remarkable radical-scavenging activities in vitro. Therefore, the aim of the
      present study was to investigate the effect of polyphenol-containing azuki bean
      extract (ABE) on systolic blood pressure (SBP) and macrophage infiltration in the
      heart and kidney of spontaneously hypertensive rats (SHR). 2. Spontaneously
      hypertensive rats and control normotensive Wistar-Kyoto (WKY) rats were divided
      into two groups fed either 0 or 0.8% ABE in their diets. Tail SBP and macrophage
      kinetics in the heart and kidney were examined. 3. The SBP of the SHR group was
      higher than that of age-matched WKY rats throughout the treatment period. After 8
      weeks of treatment, the increased SBP in ABE-treated SHR was significantly less
      than that in untreated SHR. 4. Nicotinamide adenine dinucleotide (NADH) or
      nicotinamide adenine dinucleotide phosphate (NADPH)-stimulated superoxide (O2-)
      production was enhanced in the kidney and heart in SHR and WKY rats compared with
      levels in the absence of NADH or NADPH. The NADPH-stimulated superoxide (O2-)
      levels in the kidney in untreated SHR was significantly higher than that in
      untreated WKY rats. The (O2-) levels in ABE-treated SHR were significantly
      decreased compared with the untreated SHR group. 5. In immunohistochemical
      analyses, the number of macrophages in the heart and in the glomeruli and
      tubulointerstitium of the kidney was significantly higher in ABE-untreated SHR
      than in ABE-untreated WKY rats. Conversely, there was a significant decrease in
      the number of macrophages in ABE-treated SHR compared with the untreated SHR.
      There were significant positive correlations between SBP and the number of ED1
      positive macrophages in the heart and tubulointerstitial and glomerular areas of
      the kidney in WKY rats and SHR. 6. In conclusion, the results of the present
      study suggest that ABE attenuates the elevation of SBP and macrophage
      infiltration in the heart, as well as in the glomeruli and tubulointerstitium of
      the kidney, in our SHR model.

PMID- 18047627
TI  - Methylene blue increases contralateral testicular ischaemia-reperfusion injury
      after unilateral testicular torsion.
AB  - 1. Testicular ischaemia-reperfusion injury is commonly seen in childhood.
      Infertility occurs in 25% of patients after unilateral testicular ischaemia. It
      is has been reported that methylene blue has a positive effect in the reparation
      of ischaemia-reperfusion injury in different tissues. Therefore, we hypothesized
      that methylene blue may prevent the hazardous effects of ischaemia-reperfusion
      injury in testicular tissue after unilateral testicular torsion. 2. Thirty-two
      prepubertal Wistar-albino rats were divided into four groups. Testicular torsion
      was created by rotating the right testis 720 degrees in a clockwise direction for
      5 h in all groups except for Group C, which was the sham control group. In Group
      T, bilateral orchiectomy was performed following the torsion period. In Group TD,
      both testes were removed 5 days after the torsion period. In Group MB, methylene
      blue (1 mg/kg, i.p.) was administered 40 min before detorsion and once daily over
      5 days; then, both testes were harvested. Tissue levels of malondialdehyde (MDA),
      serum levels of creatine kinase (CK), mean testicular biopsy score (MTBS) and
      mean seminifer tubule diameter (MSTD) were determined. 3. There was a significant
      difference in MTBS between Groups T and TD (P < 0.05) in both ipsilateral and
      contralateral testes. In the contralateral testis, treatment with methylene blue
      decreased MTBS and MSTD (P < 0.05) and increased MDA levels (P < 0.05). In Group
      T, mean serum CK concentrations were higher than in any of the other groups (P <
      0.05). 4. After 5 h of unilateral testicular torsion and a 5 day reperfusion
      period, serious tissue damage occurred on both the ipsilateral and contralateral
      sides. Serum CK concentrations may be an indicator for ischaemia, but not for
      ischaemia-reperfusion injury. Contrary to our hypothesis, methylene blue
      increased contralateral testicular damage after unilateral testicular torsion and
      exacerbated oxidative events.

PMID- 18047628
TI  - Immunochemical characterization of the functional constituents of Tripterygium
      wilfordii contributing to its anti-inflammatory property.
AB  - 1. Tripterygium wilfordii (TW) contains bioactive compounds that possess
      immunosuppressive properties. These compounds are considered to be potential
      drugs in the treatment of acute graft rejections. However, their structure
      activity relationships remain unknown. 2. The aim of the present study was to
      delineate the molecular moieties of triptolide that could account for its ability
      to inhibit inflammatory responses. In this context, purified TW active compounds
      (triptolide and triptonide) and synthetic triptolide derivatives were prepared to
      investigate the structure-activity relationships of triptolide. To this end, rat
      splenocytes were treated with increasing concentrations of the compounds and then
      allogenically stimulated using a mixed lymphocyte reaction to determine their
      antiproliferative activities. From the results, the IC50 value of each compound
      was calculated. 3. Modification of the beta-hydroxyl group at the C-14 position
      of the triptolide molecule significantly affected the immunosuppressive activity
      of T59, as demonstrated by a sevenfold increase of the IC50. Conversely,
      reduction of the gamma-butyrolactone group in T60 and T61 completely abrogated
      the antiproliferative effect. Alterations in the C-14 beta-hydroxyl and gamma
      butyrolactone groups also resulted in reduced cytotoxicity. 4. The present
      findings demonstrate that the C-14 beta-hydroxyl and gamma-butyrolactone moieties
      of the triptolide molecule are crucial for its anti-inflammatory properties and
      cytotoxicity and are responsible for the compound's antiproliferative activity.

PMID- 18047629
TI  - Combined spinal and epidural anaesthesia with chloroprocaine for hysterectomy.
AB  - 1. The aim of the present study was to determine the clinical efficacy and safety
      of chloroprocaine (CP) for gynaecological surgery. 2. One hundred and twenty
      gynaecological patients scheduled for hysterectomy were divided randomly into
      four groups: Group A (n = 30), 2.5% CP 1.0 mL; Group B (n = 30), 2.5% CP 1.2 mL;
      Group C (n = 30), 2.5% CP 1.4 mL; and Group D (n = 30), 2.5% CP 1.6 mL. The dose
      of CP used in each group was mixed with 1 mL vehicle containing 5% glucose and
      1.5% ephedrine. Spinal anaesthesia was achieved by lumbar puncture in the L2-3
      interspace and injection of the mixture. Wherever necessary, CP (2.5%) was used
      for epidural anaesthesia. 3. Although the times to onset and peak effect, as well
      as the grade of motor block of the lower limbs (Bromage scale), were similar
      among the four groups, the level of the highest sensory nerve block increased
      gradually, from T7 (+/- 1), T6 (+/- 1), T4 (+/- 1) to T3 (+/- 1) in Groups A, B,
      C and D, respectively. The rate of unsatisfactory spinal anaesthesia was 80 and
      16.7% in Groups A and B, respectively, and consequently epidural anaesthesia was
      superimposed in those patients for surgery to start. Spinal anaesthesia was very
      satisfactory for surgery in Groups C and D. In contrast, the incidence of
      hypotension in Groups B, C and D was 6.7, 16.7 and 67.7%, respectively; however,
      respiratory depression only occurred in Group D in nine cases (30%). No other
      adverse events or neurologic deficits were found. 4. The present results suggest
      that 30-35 mg CP in a total volume of 2.2-2.4 mL used for spinal anaesthesia in
      hysterectomy is safe and efficient. The combination of spinal and epidural
      anaesthesia with 2.5% CP can achieve 100% satisfactory anaesthesia for this type
      of surgery.

PMID- 18047630
TI  - Hyperoxia confers myocardial protection in mechanically ventilated rats through
      the generation of free radicals and opening of mitochondrial ATP-sensitive
      potassium channels.
AB  - 1. One hour exposure to hyperoxia has been shown previously to limit a subsequent
      ischaemia-reperfusion injury in spontaneously breathing rats. We tested the
      cardioprotective effect of a shorter period of hyperoxia during mechanical
      ventilation and the possible contribution of reactive oxygen species (ROS) and
      mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels. 2. Mechanically
      ventilated rats were exposed to normoxia (Fi O2 = 0.3) or hyperoxia (Fi O2 = 1.0)
      for 30 min and pH, P CO2, PO2, heart rate, airway and blood pressure were
      measured at baseline and after 30 min mechanical ventilation. Isolated hearts
      were subsequently subjected to 30 min ischaemia and 120 min reperfusion. Infarct
      size and left ventricular end-diastolic pressure (LVEDP), developed pressure
      (LVDP) and coronary flow (CF) were measured. In order to investigate the role of
      ROS and KATP channels within the mechanism leading to cardioprotection, the free
      radical scavenger N-acetylcysteine (NAC; 150 mg/kg) was infused in mechanically
      ventilated rats and the KATP channel blockers glibenclamide (200 mmol/L) or 5
      hydroxydecanoate (10 mmol/L) were infused in isolated hearts immediately before
      ischaemia. 3. No differences were detected in P CO2, pH, heart rate, airway and
      blood pressure between the groups. However, the PO2 in hyperoxic groups was
      significantly higher compared with that in normoxic groups (P < 0.01). After 30
      min ischaemia, we found that hyperoxic preconditioning significantly improved CF
      (P < 0.01), LVDP (P < 0.01) and LVEDP (P < 0.01) and reduced the extent of
      infarct size in the reperfused heart compared with the normoxic group (P < 0.01).
      When rats were pretreated either with NAC before hyperoxic ventilation or with
      K(ATP) channel blockers before ischaemia, myocardial protection was abolished. 4.
      Hyperoxic mechanical ventilation, prior to ischaemia, reduces myocardial
      reperfusion injury. This is likely to occur through the induction of oxidative
      stress, which leads to myocyte mitoKATP channel opening.

PMID- 18047631
TI  - Peroxisome proliferator-activated receptor-gamma agonists attenuate angiotensin
      II-induced collagen type I expression in adventitial fibroblasts.
AB  - 1. Angiotensin (Ang) II-mediated oxidative stress may be important in enhanced
      adventitial fibroblast collagen formation. The aim of the present study was to
      test whether PPAR-gamma agonists 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d
      PGJ2) and pioglitazone could alter AngII-induced collagen type I formation in
      vascular adventitial fibroblasts via reactive oxygen species (ROS). 2. Vascular
      adventitial fibroblasts were isolated from rat thoracic aortas of male Sprague
      Dawley rats and treated with different concentrations of AngII for different
      periods of time. The expression of collagen type I induced by AngII was examined
      by western blot. Expression of PPAR-gamma mRNA was examined by reverse
      transcription-polymerase chain reaction (RT-PCR). Intracellular ROS generation
      was measured by flow cytometry. Activation of transcription factors nuclear
      factor (NF)-kappaB and activator protein (AP)-1 was assessed by an
      electrophoretic mobility shift assay. 3. Angiotensin II increased expression of
      collagen type I in a time- and dose-dependent manner in adventitial fibroblasts.
      In addition, AngII stimulated intracellular generation of ROS in adventitial
      fibroblasts. Pretreatment of cells with 15d-PGJ2 and pioglitazone attenuated
      collagen type I expression and generation of ROS induced by AngII, respectively.
      Moreover, we observed that N-acetylcysteine inhibited collagen type I expression
      induced by AngII as did the PPAR-gamma agonists. Angiotensin II treatment
      activated the redox-sensitive transcription factors NF-kappaB and AP-1, whereas
      pretreatment with 15d-PGJ2 and pioglitazone reduced the AngII-induced DNA-binding
      activity of NF-kappaB but not AP-1. 4 Our data demonstrate that the PPAR-gamma
      agonists 15d-PGJ2 and pioglitazone attenuate AngII-mediated collagen type I
      expression in adventitial fibroblasts, which may be mediated by the modulation of
      ROS release and the redox-sensitive transcription factor NF-kappaB.

PMID- 18047632
TI  - Correlation of body composition with cardiac function and arterial compliance.
AB  - 1. The aim of the present study was to examine the correlation of precisely
      measured body composition with cardiac function and arterial compliance. 2. Body
      composition was determined in a total of 325 healthy volunteers (217 men, 108
      women) with an average age of 48 years using bioelectrical impedance analysis
      (BIA). Multiple body components, such as water, fat, mineral, protein and
      intracellular and extracellular liquid, were included in our measurements. Aortic
      pulse wave velocity (PWV) was evaluated to assess arterial stiffness, whereas
      cardiac function was examined by echocardiography. Levels of serum glucose, high
      density lipoprotein-cholesterol, triglycerides, creatinine and uric acid were
      measured to evaluate the cardiovascular risk of the participants. 3. All
      parameters of body composition, especially body fat rate (BFR; body fat
      mass/weight, were closely correlated with arterial function as evaluated by PWV.
      However, plasma homocysteine, one of the independent risk factors for
      cardiovascular diseases, failed to exhibit any correlation with arterial
      compliance. Notably, the BFR was found to be associated with both systolic and
      diastolic cardiac function with high correlation coefficients. Individuals with
      normal systolic and diastolic function were characterized with lower PWV values
      for the aorta, as well as arm and inferior arteries, indicating better arterial
      compliance. Body fat mass and BFR were significantly lower in subjects with
      normal systolic function than those with defective arterial compliance. 4. In
      conclusion, our data provide new insights into the intrinsic correlation between
      body composition and cardiac function, as well as arterial compliance,
      implicating a potential application of BIA in the clinical prediction and
      diagnosis of cardiovascular disease.

PMID- 18047633
TI  - Pressor and non-pressor effects of sodium loading on stroke in stroke-prone
      spontaneously hypertensive rats.
AB  - 1. Aetiological studies have shown that sodium loading increases both blood
      pressure and death from stroke. The present study was designed to investigate the
      pressor and non-pressor effects of sodium loading on stroke in stroke-prone
      spontaneously hypertensive rats (SHRSP). 2. Eighty-five female SHRSP were used.
      Forty-nine SHRSP, aged 5 months, were randomly divided into two groups with or
      without sodium loading and their survival times were recorded. Thirty-six SHRSP,
      aged 3 months, were randomly divided into two groups and were instrumented to
      determine blood pressure, heart period and baroreflex sensitivity (BRS) after 4
      months of sodium loading or normal rat chow. After determination of BRS, blood
      samples were collected for the measurement of tumour necrosis factor (TNF),
      interleukin (IL)-1beta, IL-6 and angiotensin (Ang) II and brains were dissected
      for light microscopic examination. 3. Over the 15 month period, the mortality of
      control SHRSP was 37.5%, which reached 80.0% in the sodium loading group.
      Compared with the control group, blood pressure was increased but BRS was
      significantly decreased (P < 0.001) in sodium-loaded rats. Levels of IL-1beta, IL
      6 and AngII were all significantly increased (P < 0.05) in the sodium-loaded
      rats. Sodium loading also markedly increased the number of cerebral aneurysms.
      Multivariate regression analysis showed that IL-6 was the most significant factor
      related to aneurysm formation. 4. Sodium loading increases death from stroke in
      SHRSP. The increased blood pressure, impaired BRS, inflammatory reaction and the
      formation of cerebral aneurysms may contribute to the development of stroke.

PMID- 18047634
TI  - Induction of inflammatory cytokine release from human umbilical vein endothelial
      cells by agonists of proteinase-activated receptor-2.
AB  - 1. Human endothelial cells express proteinase-activated receptor-2 (PAR-2),
      inflammatory cytokines and trypsin (EC 3.4.21.4). However, little is known about
      the mechanism through which trypsin induces cytokine release from endothelial
      cells. 2. In the present study, we investigated the effect of trypsin on cytokine
      release from primary cultures of human umbilical vein endothelial cells (HUVEC)
      using an antibody based protein microarray and ELISA. 3. The results showed that
      1 microg/mL trypsin induced release of 32 different inflammatory factors, whereas
      100 micromol/L Ser-Leu-Ile-Gly-Lys-Val-NH2 (SLIGKV-NH2) only stimulated secretion
      of 16 inflammatory factors from HUVEC, as assessed by an antibody based protein
      microarray. Because the release of interleukin (IL)-1a, IL-8, IL-10 and IL-12 was
      markedly increased following PAR-2 activation, their release was investigated
      further using ELISA. Increases in release of up to approximately 4.8-, 4.3-, 4.1-
      and 1.8-fold were observed for IL-1a, IL-10, IL-12 and IL-8, respectively, when
      HUVEC were challenged with trypsin for 16 h. Agonist peptides of PAR-2, namely
      SLIGKV-NH2 and trans-cinnamoyl-Leu-Ile-Gly-Arg-Leu-Orn-NH2 (tc-LIGRLO-NH2), also
      provoked significant release of IL-8. Trypsin-induced cytokine release was
      inhibited by its inhibitors soybean trypsin inhibitor, alpha1-antitrypsin and the
      inhibitor peptide of PAR-2 Phe-Ser-Leu-Leu-Arg-Tyr-NH2 (FSLLRY-NH2). 4. These
      data indicate the action of trypsin on HUVEC is most likely through activation of
      PAR-2, suggesting that PAR-2-related mechanisms are involved in the inflammatory
      process in humans.

PMID- 18047635
TI  - delta-Opioid receptor stimulation enhances the growth of neonatal rat ventricular
      myocytes via the extracellular signal-regulated kinase pathway.
AB  - 1. The aims of the present study were to determine whether delta-opioid receptor
      stimulation enhanced proliferation of and to investigate the role of the
      extracellular signal-regulated kinase (ERK) pathway in ventricular myocytes from
      neonatal rats. 2. At concentratins ranging from 10 nmol/L to 10 micromol/L, [D
      Ala2,D-Leu5]enkephalin (DADLE) concentration-dependently promoted myocardial
      growth and DNA synthesis and altered the cytoskeleton. 3. At 1 micromol/L, DADLE
      also increased the expression and phosphorylation of ERK. 4. These effects of 1
      micromol/L DADLE were abolished by 10 micromol/L naltrindole, a selective delta
      opioid receptor antagonist, 10 nmol/L U0126, a selective ERK antagonist, 1
      micromol/L staurosporine, an inhibitor of protein kinase (PK) C, and 100
      micromol/L Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt
      hydrate (Rp-cAMPS), an inhibitor of PKA. 5. In conclusion, delta-opioid receptor
      stimulation enhances the proliferation and development of the ventricular
      myocytes of neonatal rats. The ERK pathway and related signalling mechanisms,
      namely PKC and PKA, are involved.

PMID- 18047637
TI  - Large bowel obstruction due to sesame seed bezoar: a case report.
AB  - We report a case of a 79 year old man with a known benign anastomotic stricture
      presenting with large bowel obstruction. At laparotomy the obstruction was found
      to be caused by a large sesame seed bezoar. Seed bezoars are well known to cause
      impaction in the rectum but have never been previously reported to cause large
      bowel obstruction. We recommend that patients with known large bowel strictures
      should be advised not to eat seeds as this could ultimately lead to obstruction,
      ischaemia or perforation.

PMID- 18047639
TI  - Provider-initiated HIV testing in rural Haiti: low rate of missed opportunities
      for diagnosis of HIV in a primary care clinic.
AB  - As HIV treatment is scaled-up in resource-poor settings, the timely
      identification of persons with HIV infection remains an important challenge. Most
      people with HIV are unaware of their status, and those who are often present late
      in the course of their illness. Free-standing voluntary counseling and testing
      sites often have poor uptake of testing. We aimed to evaluate a 'provider
      initiated' HIV testing strategy in a primary care clinic in rural resource-poor
      Haiti by reviewing the number of visits made to clinic before an HIV test was
      performed in those who were ultimately found to have HIV infection. In
      collaboration with the Haitian Ministry of Health, a non-governmental
      organization (Partners In Health) scaled up HIV care in central Haiti by
      reinforcing primary care clinics, instituting provider-initiated HIV testing and
      by providing HIV treatment in the context of primary medical care, free of charge
      to patients. Among a cohort of people with HIV infection, we assessed
      retrospectively for delays in or 'missed opportunities' for diagnosis of HIV by
      the providers in one clinic. Of the first 117 patients diagnosed with HIV in one
      clinic, 100 (85%) were diagnosed at the first medical encounter. Median delay in
      diagnosis for the remaining 17 was only 62 days (IQR 19 - 122; range 1 - 272).
      There was no statistical difference in CD4 cell count between those with and
      without a delay. 3787 HIV tests were performed in the period reviewed. Provider
      initiated testing was associated with high volume uptake of HIV testing and
      minimal delay between first medical encounter and diagnosis of HIV infection. In
      scale up of HIV care, provider-initiated HIV testing at primary care clinics can
      be a successful strategy to identify patients with HIV infection.

PMID- 18047638
TI  - Adiponectin and AMP kinase activator stimulate proliferation, differentiation,
      and mineralization of osteoblastic MC3T3-E1 cells.
AB  - BACKGROUND: Adiponectin is a key mediator of the metabolic syndrome that is
      caused by visceral fat accumulation. Adiponectin and its receptors are known to
      be expressed in osteoblasts, but their actions with regard to bone metabolism are
      still unclear. In this study, we investigated the effects of adiponectin on the
      proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1
      cells. RESULTS: Adiponectin receptor type 1 (AdipoR1) mRNA was detected in the
      cells by RT-PCR. The adenosine monophosphate-activated protein kinase (AMP
      kinase) was phosphorylated by both adiponectin and a pharmacological AMP kinase
      activator, 5-amino-imidazole-4-carboxamide-riboside (AICAR), in the cells.
      AdipoR1 small interfering RNA (siRNA) transfection potently knocked down the
      receptor mRNA, and the effect of this knockdown persisted for as long as 10 days
      after the transfection. The transfected cells showed decreased expressions of
      type I collagen and osteocalcin mRNA, as determined by real-time PCR, and reduced
      ALP activity and mineralization, as determined by von Kossa and Alizarin red
      stainings. In contrast, AMP kinase activation by AICAR (0.01-0.5 mM) in wild-type
      MC3T3-E1 cells augmented their proliferation, differentiation, and
      mineralization. BrdU assay showed that the addition of adiponectin (0.01-1.0
      mug/ml) also promoted their proliferation. Osterix, but not Runx-2, appeared to
      be involved in these processes because AdipoR1 siRNA transfection and AICAR
      treatments suppressed and enhanced osterix mRNA expression, respectively.
      CONCLUSION: Taken together, this study suggests that adiponectin stimulates the
      proliferation, differentiation, and mineralization of osteoblasts via the AdipoR1
      and AMP kinase signaling pathways in autocrine and/or paracrine fashions.

PMID- 18047640
TI  - Glucocorticoid receptor gene polymorphisms associated with progression of lung
      disease in young patients with cystic fibrosis.
AB  - BACKGROUND: The variability in the inflammatory burden of the lung in cystic
      fibrosis (CF) patients together with the variable effect of glucocorticoid
      treatment led us to hypothesize that glucocorticoid receptor (GR) gene
      polymorphisms may affect glucocorticoid sensitivity in CF and, consequently, may
      contribute to variations in the inflammatory response. METHODS: We evaluated the
      association between four GR gene polymorphisms, TthIII, ER22/23EK, N363S and
      BclI, and disease progression in a cohort of 255 young patients with CF.
      Genotypes were tested for association with changes in lung function tests,
      infection with Pseudomonas aeruginosa and nutritional status by multivariable
      analysis. RESULTS: A significant non-corrected for multiple tests association was
      found between BclI genotypes and decline in lung function measured as the forced
      expiratory volume in one second (FEV1) and the forced vital capacity (FVC).
      Deterioration in FEV1 and FVC was more pronounced in patients with the BclI GG
      genotype compared to the group of patients with BclI CG and CC genotypes (p =
      0.02 and p = 0.04 respectively for the entire cohort and p = 0.01 and p = 0.02
      respectively for F508del homozygous patients). CONCLUSION: The BclI polymorphism
      may modulate the inflammatory burden in the CF lung and in this way influence
      progression of lung function.

PMID- 18047641
TI  - Application of phage display to high throughput antibody generation and
      characterization.
AB  - We have created a high quality phage display library containing over 1010 human
      antibodies and describe its use in the generation of antibodies on an
      unprecedented scale. We have selected, screened and sequenced over 38,000
      recombinant antibodies to 292 antigens, yielding over 7,200 unique clones. 4,400
      antibodies were characterized by specificity testing and detailed sequence
      analysis and the data/clones are available online. Sensitive detection was
      demonstrated in a bead based flow cytometry assay. Furthermore, positive staining
      by immunohistochemistry on tissue microarrays was found for 37% (143/381) of
      antibodies. Thus, we have demonstrated the potential of and illuminated the
      issues associated with genome-wide monoclonal antibody generation.

PMID- 18047642
TI  - Recently enlisted patients in general practice use more health care resources.
AB  - BACKGROUND: The continuity of care is one of the cornerstones of general
      practice. General practitioners find personal relationships with their patients
      important as they enable them to provide a higher quality of care. A long-lasting
      relationship with patients is assumed to be a prior condition for attaining this
      high quality. We studied the differences in use of care between recently enlisted
      patients and those patients who have been enlisted for a longer period. METHODS:
      104 general practices in the Netherlands participated the study. We performed a
      retrospective cohort study in which patients who have been enlisted for less than
      1 year (n = 10,102) were matched for age, sex and health insurance with patients
      who have been enlisted for longer in the same general practice. The two cohorts
      were compared with regard to the number of contacts with the general practice,
      diagnoses, rate of prescribing, and the referral rate in a year. These variables
      were chosen as indicators of differences in the use of care. RESULTS: In the year
      following their enlistment, a higher percentage of recently enlisted patients had
      at least one contact with the practice, received a prescription or was referred.
      They also had a higher probability of receiving a prescription for an antibiotic.
      Furthermore, they had a higher mean number of contacts and referrals, but not a
      higher mean number of prescriptions. CONCLUSION: Recently enlisted patients used
      more health care resources in the first year after their enlistment compared to
      patients enlisted longer. This could not be explained by differences in health.

PMID- 18047643
TI  - Does training family physicians in shared decision making promote optimal use of
      antibiotics for acute respiratory infections? Study protocol of a pilot clustered
      randomised controlled trial.
AB  - BACKGROUND: In North America, although it varies according to the specific type
      of acute respiratory infections (ARI), use of antibiotics is estimated to be well
      above the expected prevalence of bacterial infections. The objective of this
      pilot clustered randomized controlled trial (RCT) is to assess the feasibility of
      a larger clustered RCT aiming at evaluating the impact of DECISION+, a continuing
      professional development (CPD) program in shared decision making, on the optimal
      use of antibiotics in the context of ARI. METHODS/DESIGN: This pilot study is a
      cluster RCT conducted with family physicians from Family Medicine Groups (FMG) in
      the Quebec City area, Canada. Participating FMG are randomised to an immediate
      DECISION+ group, a CPD program in shared decision making, (experimental group),
      or a delayed DECISION+ group (control group). Data collection involves recruiting
      five patients consulting for ARI per physician from both study groups before
      (Phase 1) and after (Phase 2) exposure of the experimental group to the DECISION+
      program, and after exposure of the control group to the DECISION+ program (Phase
      3). The primary outcome measures to assess the feasibility of a larger RCT
      include: 1) proportion of contacted FMG that agree to participate; 2) proportion
      of recruited physicians who participate in the DECISION+ program; 3) level of
      satisfaction of physicians regarding DECISION+; and 4) proportion of missing data
      in each data collection phase. Levels of agreement of the patient-physician dyad
      on the Decisional Conflict Scale and physicians' prescription profile for ARI are
      performed as secondary outcome measures. DISCUSSION: This study protocol is
      informative for researchers and clinicians interested in designing and/or
      conducting clustered RCT with FMG regarding training of physicians in shared
      decision making. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00354315.

PMID- 18047644
TI  - Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong
      immune response at the adult stage.
AB  - BACKGROUND: Vaccination of neonates is generally difficult due to the immaturity
      of the immune system and consequent higher susceptibility to tolerance induction.
      Genetic immunization has been described as an alternative to trigger a stronger
      immune response in neonates, including significant Th1 polarization. In this
      investigation we analysed the potential use of a genetic vaccine containing the
      heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against
      tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic
      integration and immunogenicity were evaluated. METHODS: Hsp65 message and genomic
      integration were evaluated by RT-PCR and Southern blot, respectively.
      Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific
      induction of antibodies and cytokines, both quantified by ELISA. RESULTS: This
      DNA vaccine was transcribed by muscular cells of neonate mice without integration
      into the cellular genome. Even though this vaccine was not strongly immunogenic
      when entirely administered (three doses) during early animal's life, it was not
      tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn
      mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters
      administered later, at the adult life. CONCLUSION: These results suggest that
      pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime
      boost similar strategies to control TB. However, priming with BCG or pVAXhsp65,
      directed the ensuing immune response triggered by an heterologous or homologous
      booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL
      12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are
      probably required to increase the priming towards Th1 polarization to ensure
      control of tuberculosis infection.

PMID- 18047645
TI  - X-chromosome tiling path array detection of copy number variants in patients with
      chromosome X-linked mental retardation.
AB  - BACKGROUND: Aproximately 5-10% of cases of mental retardation in males are due to
      copy number variations (CNV) on the X chromosome. Novel technologies, such as
      array comparative genomic hybridization (aCGH), may help to uncover cryptic
      rearrangements in X-linked mental retardation (XLMR) patients. We have
      constructed an X-chromosome tiling path array using bacterial artificial
      chromosomes (BACs) and validated it using samples with cytogenetically defined
      copy number changes. We have studied 54 patients with idiopathic mental
      retardation and 20 controls subjects. RESULTS: Known genomic aberrations were
      reliably detected on the array and eight novel submicroscopic imbalances, likely
      causative for the mental retardation (MR) phenotype, were detected. Putatively
      pathogenic rearrangements included three deletions and five duplications (ranging
      between 82 kb to one Mb), all but two affecting genes previously known to be
      responsible for XLMR. Additionally, we describe different CNV regions with
      significant different frequencies in XLMR and control subjects (44% vs. 20%).
      CONCLUSION: This tiling path array of the human X chromosome has proven
      successful for the detection and characterization of known rearrangements and
      novel CNVs in XLMR patients.

PMID- 18047646
TI  - The geographical distribution of lymphatic filariasis infection in Malawi.
AB  - Mapping distribution of lymphatic filariasis (LF) is a prerequisite for planning
      national elimination programmes. Results from a nation wide mapping survey for
      lymphatic filariasis (LF) in Malawi are presented. Thirty-five villages were
      sampled from 23 districts excluding three districts (Karonga, Chikwawa and
      Nsanje) that had already been mapped and Likoma, an Island, where access was not
      possible in the time frame of the survey. Antigenaemia prevalence [based on
      immunochromatographic card tests (ICT)] ranged from 0% to 35.9%. Villages from
      the western side of the country and distant from the lake tended to be of lower
      prevalence. The exception was a village in Mchinji district on the Malawi-Zambia
      border where a prevalence of 18.2% was found. In contrast villages from lake
      shore districts [Salima, Mangochi, Balaka and Ntcheu (Bwanje valley)] and
      Phalombe had prevalences of over 20%.A national map is developed which
      incorporates data from surveys in Karonga, Chikwawa and Nsanje districts, carried
      out in 2000. There is a marked decline in prevalence with increasing altitude.
      Further analysis revealed a strong negative correlation (R2 = 0.7 p < 0.001)
      between altitude and prevalence. These results suggest that the lake shore,
      Phalombe plain and the lower Shire valley will be priority areas for the Malawi
      LF elimination programme. Implications of these findings as regards implementing
      a national LF elimination programme in Malawi are discussed.

PMID- 18047647
TI  - Monitoring lymphatic filariasis interventions: Adult mosquito sampling, and
      improved PCR - based pool screening method for Wuchereria bancrofti infection in
      Anopheles mosquitoes.
AB  - BACKGROUND: Monitoring and evaluation are essential to the successful
      implementation of mass drug administration programmes for LF elimination.
      Monitoring transmission when it is low requires both large numbers of mosquito
      vectors and sensitive methods for detecting Wuchereria bancrofti infections in
      them. PCR-based methods are preferred over classical dissections but the best
      protocol so far achieved detection of one L3 Wuchereria bancrofti larva in a pool
      of 35-50 Anopheles mosquitoes. It also lacks consistency and remains still a
      costly tool. Hence we decided to improve upon this to achieve detection in a pool
      of 100 or more by enhancing the quality of the template DNA. Prior to this we
      also evaluated three vector sampling methods in the context of numbers for
      monitoring. METHODS: Human landing, pyrethrium spray and light traps catches were
      conducted concurrently at sites in an LF endemic district in Ghana and the
      numbers obtained compared. Two DNA extraction methods; Bender buffer and
      phenol/chloroform purification, and DNAeasy Tissue kit (Quaigen Inc) were used on
      pools of 25, 50, 75 100 and 150 mosquitoes each seeded with one L3 or its
      quivalent amount of DNA. Then another set of extracted DNA by the two methods was
      subjected to Dynal bead purification method (using capture oligonucleotide
      primers). These were used as template DNA in PCR to amplify W. bancrofti
      sequences. The best PCR result was then evaluated in the field at five sites by
      comparing its results (infections per 1000 mosquitoes) with that of dissection of
      roughly equal samples sizes. RESULTS: The largest numbers of mosquitoes were
      obtained with the human landing catches at all the sites sampled. Although PCR
      detection of one L3 in pools of 25, 50 and 75 mosquitoes was consistent
      irrespective of the extraction method, that of one L3 in 100 was only achieved
      with the kit-extracted DNA/Dynal bead purification method. Infections were found
      at only two sites by both dissection and pool-screening being 14.3 and 19 versus
      13.4 and 20.1 per 1000 Anopheles mosquitoes respectively, which were not
      statistically significant DISCUSSION AND CONCLUSION: HLC still remains the best
      option for sampling for the large numbers of mosquitoes required for monitoring
      transmission during MDA programmes, when vector population densities are high and
      classical indices of transmission are required. One - in - 100 detection is an
      improvement on previous PCR pool-screening methods, which in our opinion was a
      result of the introduction of the extra step of parasite DNA capture using
      Dynal/beads. As pool sizes increase the insects DNA will swamp parasite DNA
      making the latter less available for an efficient PCR, therefore we propose
      either additional steps of parasite DNA capture or real-time PCR to improve
      further the pool screening method. The study also attests also to the
      applicability of Katholi et al's algorithm developed for determining
      onchocerciasis prevalence in LF studies.

PMID- 18047648
TI  - Long-term stability of RNA in post-mortem bovine skeletal muscle, liver and
      subcutaneous adipose tissues.
AB  - BACKGROUND: Recovering high quality intact RNA from post-mortem tissue is of
      major concern for gene expression studies in animals and humans. Since the
      availability of post-mortem tissue is often associated with substantial delay, it
      is important that we understand the temporal variation in the stability of total
      RNA and of individual gene transcripts so as to be able to appropriately
      interpret the data generated from such studies. Hence, the objective of this
      experiment was to qualitatively and quantitatively assess the integrity of total
      and messenger RNA extracted from bovine skeletal muscle, subcutaneous adipose
      tissue and liver stored at 4 degrees C at a range of time points up to 22 days
      post-mortem. These conditions were designed to mimic the environment prevailing
      during the transport of beef from the abattoir to retail outlets. RESULTS: The
      28S and 18S rRNA molecules of total RNA were intact for up to 24 h post-mortem in
      liver and adipose tissues and up to 8 days post-mortem in skeletal muscle. The
      mRNA of housekeeping genes (GAPDH and ACTB) and two diet-related genes (RBP5 and
      SCD) were detectable up to 22 days post-mortem in skeletal muscle. While the mRNA
      stability of the two housekeeping genes was different in skeletal muscle and
      liver, they were similar to each other in adipose tissue. After 22 days post
      mortem, the relative abundance of RBP5 gene was increased in skeletal muscle and
      in adipose tissue and decreased in liver. During this period, the relative
      abundance of SCD gene also increased in skeletal muscle whereas it decreased in
      both adipose tissue and liver. CONCLUSION: Stability of RNA in three tissues
      (skeletal muscle, subcutaneous adipose tissue and liver) subjected to long-term
      post-mortem storage at refrigeration temperature indicated that skeletal muscle
      can be a suitable tissue for recovering biologically useful RNA for gene
      expression studies even if the tissue is subjected to post-mortem storage for
      weeks, whereas adipose tissue and liver should be processed within 24 hours post
      mortem.

PMID- 18047649
TI  - Biased exonization of transposed elements in duplicated genes: A lesson from the
      TIF-IA gene.
AB  - BACKGROUND: Gene duplication and exonization of intronic transposed elements are
      two mechanisms that enhance genomic diversity. We examined whether there is less
      selection against exonization of transposed elements in duplicated genes than in
      single-copy genes. RESULTS: Genome-wide analysis of exonization of transposed
      elements revealed a higher rate of exonization within duplicated genes relative
      to single-copy genes. The gene for TIF-IA, an RNA polymerase I transcription
      initiation factor, underwent a humanoid-specific triplication, all three copies
      of the gene are active transcriptionally, although only one copy retains the
      ability to generate the TIF-IA protein. Prior to TIF-IA triplication, an Alu
      element was inserted into the first intron. In one of the non-protein coding
      copies, this Alu is exonized. We identified a single point mutation leading to
      exonization in one of the gene duplicates. When this mutation was introduced into
      the TIF-IA coding copy, exonization was activated and the level of the protein
      coding mRNA was reduced substantially. A very low level of exonization was
      detected in normal human cells. However, this exonization was abundant in most
      leukemia cell lines evaluated, although the genomic sequence is unchanged in
      these cancerous cells compared to normal cells. CONCLUSION: The definition of the
      Alu element within the TIF-IA gene as an exon is restricted to certain types of
      cancers; the element is not exonized in normal human cells. These results further
      our understanding of the delicate interplay between gene duplication and
      alternative splicing and of the molecular evolutionary mechanisms leading to
      genetic innovations. This implies the existence of purifying selection against
      exonization in single copy genes, with duplicate genes free from such constrains.

PMID- 18047650
TI  - The effectiveness of motorised lumbar traction in the management of LBP with
      lumbo sacral nerve root involvement: a feasibility study.
AB  - BACKGROUND: Traction is commonly used for the treatment of low back pain (LBP),
      predominately with nerve root involvement; however its benefits remain to be
      established. The aim of this study was to test the feasibility of a pragmatic
      randomized controlled trial to compare the difference between two treatment
      protocols (manual therapy, exercise and advice, with or without traction) in the
      management of acute/sub acute LBP with 'nerve root' involvement. METHODS: 30 LBP
      patients with nerve root pain were recruited and randomly assigned to one of two
      treatment groups. Primary outcome measures were the: McGill pain questionnaire,
      Roland Morris disability questionnaire, and the SF36 Questionnaire; recorded at
      baseline, discharge, 3 and 6 months post-discharge. RESULTS: 27 patients
      completed treatment with a loss of another four patients at follow up. Intention
      to treat analysis demonstrated an improvement in all outcomes at follow up points
      but there appeared to be little difference between the groups. CONCLUSION: This
      study has shown that a trial recruiting patients with 'nerve root' problems is
      feasible. Further research based upon a fully powered trial is required to
      ascertain if the addition of traction has any benefit in the management of these
      patients. TRIAL REGISTRATION:  REGISTRATION NUMBER: ISRCTN78417198.

PMID- 18047651
TI  - Culture-confirmed childhood tuberculosis in Cape Town, South Africa: a review of
      596 cases.
AB  - BACKGROUND: The clinical, radiological and microbiological features of culture
      confirmed childhood tuberculosis diagnosed at two referral hospitals are
      described. METHODS: Cultures of Mycobacterium tuberculosis from children less
      than 13 years of age at Tygerberg and Red Cross Children's Hospitals, Cape Town,
      South Africa, were collected from March 2003 through February 2005. Folder review
      and chest radiography were performed and drug susceptibility tests done. RESULTS:
      Of 596 children (median age 31 months), 330 (55.4%) were males. Of all children,
      281 (47.1%) were HIV-uninfected, 133 (22.3%) HIV-infected and 182 (30.5%) not
      tested. Contact with infectious tuberculosis adults was recorded in 295 (49.5%)
      children. Missed opportunities for chemoprophylaxis were present in 117/182
      (64.3%) children less than 5 years of age. Extrathoracic TB was less common in
      HIV-infected than in HIV-uninfected children (49/133 vs. 156/281; odds ratio
      0.50, 95% confidence interval 0.32-0.78). Alveolar opacification (84/126 vs.
      128/274; OR 1.85, 95%CI 1.08-3.19) and cavitation (33/126 vs. 44/274; OR 2.28,
      95%CI 1.44-3.63) were more common in HIV-infected than in HIV-uninfected
      children. Microscopy for acid-fast bacilli on gastric aspirates and sputum was
      positive in 29/142 (20.4%) and 40/125 (32.0%) children, respectively. Sixty-seven
      of 592 (11.3%) children's isolates showed resistance to isoniazid and/or
      rifampicin; 43 (7.3%) were isoniazid-monoresistant, 2 (0.3%) rifampicin
      monoresistant and 22 (3.7%) multidrug-resistant. Death in 41 children (6.9%) was
      more common in HIV-infected children and very young infants. CONCLUSION: HIV
      infection and missed opportunities for chemoprophylaxis were common in children
      with culture-confirmed TB. With cavitating disease and sputum or gastric
      aspirates positive for acid-fast bacilli, children may be infectious.
      Transmission of drug-resistant TB is high in this setting.

PMID- 18047652
TI  - An EM algorithm for mapping segregation distortion loci.
AB  - BACKGROUND: Chromosomal region that causes distorted segregation ratios is
      referred to as segregation distortion locus (SDL). The distortion is caused
      either by differential representation of SDL genotypes in gametes before
      fertilization or by viability differences of SDL genotypes after fertilization
      but before genotype scoring. In both cases, observable phenotypes are distorted
      for marker loci in the chromosomal region close to the SDL. Under the
      quantitative genetics model for viability selection by proposing a continuous
      liability controlling the viability of individual, a simplex algorithm has been
      used to search for the solution in SDL mapping. However, they did not consider
      the effects of SDL on the construction of linkage maps. RESULTS: We proposed a
      multipoint maximum-likelihood method to estimate the position and the effects of
      SDL under the liability model together with both selection coefficients of marker
      genotypes and recombination fractions. The method was implemented via an
      expectation and maximization (EM) algorithm. The superiority of the method
      proposed under the liability model over the previous methods was verified by a
      series of Monte Carlo simulation experiments, together with a working example
      derived from the MAPMAKER/QTL software. CONCLUSION: Our results suggested that
      the new method can serve as a powerful alternative to existing methods for SDL
      mapping. Under the liability model, the new method can simultaneously estimate
      the position and the effects of SDL as well as the recombinant fractions between
      adjacent markers, and also be used to probe into the genetic mechanism for the
      bias of uncorrected map distance and to elucidate the relationship between the
      viability selection and genetic linkage.

PMID- 18047653
TI  - An additional human chromosome 21 causes suppression of neural fate of
      pluripotent mouse embryonic stem cells in a teratoma model.
AB  - BACKGROUND: Down syndrome (DS), caused by trisomy of human chromosome 21 (HSA21),
      is the most common genetic cause of mental retardation in humans. Among complex
      phenotypes, it displays a number of neural pathologies including smaller brain
      size, reduced numbers of neurons, reduced dendritic spine density and plasticity,
      and early Alzheimer-like neurodegeneration. Mouse models for DS show behavioural
      and cognitive defects, synaptic plasticity defects, and reduced hippocampal and
      cerebellar neuron numbers. Early postnatal development of both human and mouse
      model DS shows the reduced capability of neuronal precursor cells to generate
      neurons. The exact molecular cause of this reduction, and the role played by
      increased dosage of individual HSA21 genes, remain unknown. RESULTS: We have
      subcutaneously injected mouse pluripotent ES cells containing a single freely
      segregating supernumerary human chromosome 21 (HSA21) into syngeneic mice, to
      generate transchromosomic teratomas. Transchromosomic cells and parental control
      cells were injected into opposite flanks of thirty mice in three independent
      experiments. Tumours were grown for 30 days, a time-span equivalent to combined
      intra-uterine, and early post-natal mouse development. When paired teratomas from
      the same animals were compared, transchromosomic tumours showed a three-fold
      lower percentage of neuroectodermal tissue, as well as significantly reduced mRNA
      levels for neuron specific (Tubb3) and glia specific (Gfap) genes, relative to
      euploid controls. Two thirds of transchromosomic tumours also showed a lack of
      PCR amplification with multiple primers specific for HSA21, which were present in
      the ES cells at the point of injection, thus restricting a commonly retained
      trisomy to less than a third of HSA21 genes. CONCLUSION: We demonstrate that a
      supernumerary chromosome 21 causes Inhibition of Neuroectodermal DIfferentiation
      (INDI) of pluripotent ES cells. The data suggest that trisomy of less than a
      third of HSA21 genes, in two chromosomal regions, might be sufficient to cause
      this effect.

PMID- 18047654
TI  - Projections from the posterolateral olfactory amygdala to the ventral striatum:
      neural basis for reinforcing properties of chemical stimuli.
AB  - BACKGROUND: Vertebrates sense chemical stimuli through the olfactory receptor
      neurons whose axons project to the main olfactory bulb. The main projections of
      the olfactory bulb are directed to the olfactory cortex and olfactory amygdala
      (the anterior and posterolateral cortical amygdalae). The posterolateral cortical
      amygdaloid nucleus mainly projects to other amygdaloid nuclei; other seemingly
      minor outputs are directed to the ventral striatum, in particular to the
      olfactory tubercle and the islands of Calleja. RESULTS: Although the olfactory
      projections have been previously described in the literature, injection of
      dextran-amines into the rat main olfactory bulb was performed with the aim of
      delimiting the olfactory tubercle and posterolateral cortical amygdaloid nucleus
      in our own material. Injection of dextran-amines into the posterolateral cortical
      amygdaloid nucleus of rats resulted in anterograde labeling in the ventral
      striatum, in particular in the core of the nucleus accumbens, and in the medial
      olfactory tubercle including some islands of Calleja and the cell bridges across
      the ventral pallidum. Injections of Fluoro-Gold into the ventral striatum were
      performed to allow retrograde confirmation of these projections. CONCLUSION: The
      present results extend previous descriptions of the posterolateral cortical
      amygdaloid nucleus efferent projections, which are mainly directed to the core of
      the nucleus accumbens and the medial olfactory tubercle. Our data indicate that
      the projection to the core of the nucleus accumbens arises from layer III; the
      projection to the olfactory tubercle arises from layer II and is much more robust
      than previously thought. This latter projection is directed to the medial
      olfactory tubercle including the corresponding islands of Calleja, an area
      recently described as critical node for the neural circuit of addiction to some
      stimulant drugs of abuse.

PMID- 18047655
TI  - A standardised protocol for texture feature analysis of endoscopic images in
      gynaecological cancer.
AB  - BACKGROUND: In the development of tissue classification methods, classifiers rely
      on significant differences between texture features extracted from normal and
      abnormal regions. Yet, significant differences can arise due to variations in the
      image acquisition method. For endoscopic imaging of the endometrium, we propose a
      standardized image acquisition protocol to eliminate significant statistical
      differences due to variations in: (i) the distance from the tissue (panoramic vs
      close up), (ii) difference in viewing angles and (iii) color correction. METHODS:
      We investigate texture feature variability for a variety of targets encountered
      in clinical endoscopy. All images were captured at clinically optimum
      illumination and focus using 720 x 576 pixels and 24 bits color for: (i) a
      variety of testing targets from a color palette with a known color distribution,
      (ii) different viewing angles, (iv) two different distances from a calf
      endometrial and from a chicken cavity. Also, human images from the endometrium
      were captured and analysed. For texture feature analysis, three different sets
      were considered: (i) Statistical Features (SF), (ii) Spatial Gray Level
      Dependence Matrices (SGLDM), and (iii) Gray Level Difference Statistics (GLDS).
      All images were gamma corrected and the extracted texture feature values were
      compared against the texture feature values extracted from the uncorrected
      images. Statistical tests were applied to compare images from different viewing
      conditions so as to determine any significant differences. RESULTS: For the
      proposed acquisition procedure, results indicate that there is no significant
      difference in texture features between the panoramic and close up views and
      between angles. For a calibrated target image, gamma correction provided an
      acquired image that was a significantly better approximation to the original
      target image. In turn, this implies that the texture features extracted from the
      corrected images provided for better approximations to the original images.
      Within the proposed protocol, for human ROIs, we have found that there is a large
      number of texture features that showed significant differences between normal and
      abnormal endometrium. CONCLUSION: This study provides a standardized protocol for
      avoiding any significant texture feature differences that may arise due to
      variability in the acquisition procedure or the lack of color correction. After
      applying the protocol, we have found that significant differences in texture
      features will only be due to the fact that the features were extracted from
      different types of tissue (normal vs abnormal).

PMID- 18047656
TI  - Enhancement of lipase activity in non-aqueous media upon immobilization on multi
      walled carbon nanotubes.
AB  - BACKGROUND: Immobilization of biologically active proteins on nanosized surfaces
      is a key process in bionanofabrication. Carbon nanotubes with their high surface
      areas, as well as useful electronic, thermal and mechanical properties,
      constitute important building blocks in the fabrication of novel functional
      materials. RESULTS: Lipases from Candida rugosa (CRL) were found to be adsorbed
      on the multiwalled carbon nanotubes with very high retention of their biological
      activity (97%). The immobilized biocatalyst showed 2.2- and 14-fold increases in
      the initial rates of transesterification activity in nearly anhydrous hexane and
      water immiscible ionic liquid [Bmim] [PF6] respectively, as compared to the
      lyophilized powdered enzyme. It is presumed that the interaction with the
      hydrophobic surface of the nanotubes resulted in conformational changes leading
      to the 'open lid' structure of CRL. The immobilized enzyme was found to give 64%
      conversion over 24 h (as opposed to 14% with free enzyme) in the formation of
      butylbutyrate in nearly anhydrous hexane. Similarly, with ionic liquid [Bmim]
      [PF6], the immobilized enzyme allowed 71% conversion as compared to 16% with the
      free enzyme. The immobilized lipase also showed high enantioselectivity as
      determined by kinetic resolution of (+/-) 1-phenylethanol in [Bmim] [PF6]. While
      free CRL gave only 5% conversion after 36 h, the immobilized enzyme resulted in
      37% conversion with > 99% enantiomeric excess. TEM studies on the immobilized
      biocatalyst showed that the enzyme is attached to the multiwalled nanotubes.
      CONCLUSION: Successful immobilization of enzymes on nanosized carriers could pave
      the way for reduced reactor volumes required for biotransformations, as well as
      having a use in the construction of miniaturized biosensensor devices.

PMID- 18047658
TI  - The effect of attitude to risk on decisions made by nurses using computerised
      decision support software in telephone clinical assessment: an observational
      study.
AB  - BACKGROUND: There is variation in the decisions made by telephone assessment
      nurses using computerised decision support software (CDSS). Variation in nurses'
      attitudes to risk has been identified as a possible explanatory factor. This
      study was undertaken to explore the effect of nurses' attitudes to risk on the
      decisions they make when using CDSS. The setting was NHS 24 which is a nationwide
      telephone assessment service in Scotland in which nurses assess health problems,
      mainly on behalf of out-of-hours general practice, and triage calls to self care,
      a service at a later date, or immediate contact with a service. METHODS: All NHS
      24 nurses were asked to complete a questionnaire about their background and
      attitudes to risk. Routine data on the decisions made by these nurses was
      obtained for a six month period in 2005. Multilevel modelling was used to measure
      the effect of nurses' risk attitudes on the proportion of calls they sent to self
      care rather than to services. RESULTS: The response rate to the questionnaire was
      57% (265/464). 231,112 calls were matched to 211 of these nurses. 16%
      (36,342/231,112) of calls were sent to self care, varying three fold between the
      top and bottom deciles of nurses. Fifteen risk attitude variables were tested,
      including items on attitudes to risk in clinical decision-making. Attitudes to
      risk varied greatly between nurses, for example 27% (71/262) of nurses strongly
      agreed that an NHS 24 nurse "must not take any risks with physical illness" while
      17% (45/262) disagreed. After case-mix adjustment, there was some evidence that
      nurses' attitudes to risk affected decisions but this was inconsistent and
      unconvincing. CONCLUSION: Much of the variation in decision-making by nurses
      using CDSS remained unexplained. There was no convincing evidence that nurses'
      attitudes to risk affected the decisions made. This may have been due to the
      limitations of the instrument used to measure risk attitude.

PMID- 18047657
TI  - Metabolic signature of breast cancer cell line MCF-7: profiling of modified
      nucleosides via LC-IT MS coupling.
AB  - BACKGROUND: Cancer, like other diseases accompanied by strong metabolic
      disorders, shows characteristic effects on cell turnover rate, activity of
      modifying enzymes and DNA/RNA modifications, resulting also in elevated amounts
      of excreted modified nucleosides. For a better understanding of the impaired RNA
      metabolism in breast cancer cells, we screened these metabolites in the cell
      culture supernatants of the breast cancer cell line MCF-7 and compared it to the
      human mammary epithelial cells MCF-10A. The nucleosides were isolated and
      analyzed via 2D-chromatographic techniques: In the first dimension by cis-diol
      specific boronate affinity extraction and subsequently by reversed phase
      chromatography coupled to an ion trap mass spectrometer. RESULTS: Besides the
      determination of ribonucleosides, additional compounds with cis-diol structure,
      deriving from cross-linked biochemical pathways, like purine-, histidine- and
      polyamine metabolism were detected. In total, 36 metabolites were identified by
      comparison of fragmentation patterns and retention time. Relation to the internal
      standard isoguanosine yielded normalized area ratios for each identified compound
      and enabled a semi-quantitative metabolic signature of both analyzed cell
      lines.13 of the identified 26 modified ribonucleosides were elevated in the cell
      culture supernatants of MCF-7 cells, with 5-methyluridine, N2,N2,7
      trimethylguanosine, N6-methyl-N6-threonylcarbamoyladenosine and 3-(3
      aminocarboxypropyl)-uridine showing the most significant differences. 1
      ribosylimidazole-4-acetic acid, a histamine metabolite, was solely found in the
      supernatants of MCF-10A cells, whereas 1-ribosyl-4-carboxamido-5-aminoimidazole
      and S-adenosylmethionine occurred only in supernatants of MCF-7 cells.
      CONCLUSION: The obtained results are discussed against the background of
      pathological changes in cell metabolism, resulting in new perspectives for
      modified nucleosides and related metabolites as possible biomedical markers for
      breast carcinoma in vivo.

PMID- 18047659
TI  - Outcomes of skin graft reconstructions with the use of Vacuum Assisted Closure
      (VAC(R)) dressing for irradiated extremity sarcoma defects.
AB  - BACKGROUND: Flaps are currently the predominant method of reconstruction for
      irradiated wounds. The usefulness of split-thickness skin grafts (STSG) in this
      setting remains controversial. The purpose of this study is to examine the
      outcomes of STSGs in conjunction with VAC therapy used in the treatment of
      irradiated extremity wounds. METHODS: The records of 17 preoperatively radiated
      patients with extremity sarcomas reconstructed with STSGs in conjunction with
      VAC(R) therapy were reviewed regarding details of radiation treatment, wound
      closure, and outcomes. RESULTS: STSGs healed without complications (>95% of the
      graft take) in 12 (71%). Minor loss (6% - 20% surface) was noted in 3 patients
      (17.6%) and complete loss in 2 (11.7%). Two patients (11.7%) required flap
      reconstructions and 12 (88%) healed without further operative procedures.
      CONCLUSION: Although flap coverage is an established treatment for radiated
      wounds, STSG in conjunction with liberal utilization of VAC therapy is an
      alternative for selected patients where acceptable soft tissue bed is preserved.
      Healing of the preoperatively radiated wounds can be achieved in the vast
      majority of such patients with minimal need for additional reconstructive
      operations.

PMID- 18047660
TI  - Upper limb impairments associated with spasticity in neurological disorders.
AB  - BACKGROUND: While upper-extremity movement in individuals with neurological
      disorders such as stroke and spinal cord injury (SCI) has been studied for many
      years, the effects of spasticity on arm movement have been poorly quantified. The
      present study is designed to characterize the nature of impaired arm movements
      associated with spasticity in these two clinical populations. By comparing
      impaired voluntary movements between these two groups, we will gain a greater
      understanding of the effects of the type of spasticity on these movements and,
      potentially a better understanding of the underlying impairment mechanisms.
      METHODS: We characterized the kinematics and kinetics of rapid arm movement in
      SCI and neurologically intact subjects and in both the paretic and non-paretic
      limbs in stroke subjects. The kinematics of rapid elbow extension over the entire
      range of motion were quantified by measuring movement trajectory and its
      derivatives; i.e. movement velocity and acceleration. The kinetics were
      quantified by measuring maximum isometric voluntary contractions of elbow flexors
      and extensors. The movement smoothness was estimated using two different
      computational techniques. RESULTS: Most kinematic and kinetic and movement
      smoothness parameters changed significantly in paretic as compared to normal arms
      in stroke subjects (p < 0.003). Surprisingly, there were no significant
      differences in these parameters between SCI and stroke subjects, except for the
      movement smoothness (p < or = 0.02). Extension was significantly less smooth in
      the paretic compared to the non-paretic arm in the stroke group (p < 0.003),
      whereas it was within the normal range in the SCI group. There was also no
      significant difference in these parameters between the non-paretic arm in stroke
      subjects and the normal arm in healthy subjects. CONCLUSION: The findings suggest
      that although the cause and location of injury are different in spastic stroke
      and SCI subjects, the impairments in arm voluntary movement were similar in the
      two spastic groups. Our results also suggest that the non-paretic arm in stroke
      subjects was not distinguishable from the normal, and might therefore be used as
      an appropriate control for studying movement of the paretic arm.

PMID- 18047661
TI  - Treatment outcome of new pulmonary tuberculosis in Guangzhou, China 1993-2002: a
      register-based cohort study.
AB  - BACKGROUND: Completion of treatment for tuberculosis (TB) is of utmost priority
      for TB control programs. The aims of this study were to evaluate the treatment
      outcome of TB cases registered in Guangzhou during the period 1993-2002, and to
      identify factors associated with treatment success. METHODS: Two (of eight)
      districts in Guangzhou were selected randomly as objects of study and their
      surveillance database was analyzed to assess the treatment outcome and identify
      factors associated with treatment success for TB cases registered in Guangzhou.
      Six treatment outcome criteria were assessed based on guidelines set by the World
      Health Organization (WHO). Logistic regression was used to estimate risk factors
      for treatment outcome. RESULTS: A total of 6743 pulmonary tuberculosis cases
      (4903 males, 1840 females) were included in this study. The treatment success
      rate (including cured and complete treatment) was 88% (95%CI 87%-89%). One
      hundred and eight-six (2.8%) patients died and 401 (5.9%) patients defaulted
      treatment. In multivariate analysis, treatment success was found to be associated
      with young age, lack of cavitation and compliance with treatment. CONCLUSION: The
      total treatment success rate in the current study was similar to the WHO target
      for all smear positive cases, while the failure rate and the default rate in 2002
      were slightly higher. Good care of elderly patients, early diagnosis of
      cavitation and compliance with treatment could improve the success rate of TB
      treatment.

PMID- 18047662
TI  - Tumor-infiltrating macrophages and dendritic cells in human colorectal cancer:
      relation to local regulatory T cells, systemic T-cell response against tumor
      associated antigens and survival.
AB  - INTRODUCTION: Although systemic T-cell responses against tumor antigens and tumor
      infiltration by T cells have been investigated in colorectal cancer (CRC), the
      initiation of spontaneous immune responses in situ is not well understood.
      Macrophages and dendritic cells (DC) play an important role as a link between
      innate and adaptive immune response. The aim of the present study was to analyze
      macrophage and DC infiltration in CRC and to investigate whether there is a
      correlation to systemic T-cell response, regulatory T cell (Treg) infiltration,
      and survival. METHODS: Immunohistological staining was performed with nine
      markers for macrophages and DC (CD68, CD163, S100, CD11c, CD208, CD209, CD123,
      CD1a, Langerin) in 40 colorectal cancer samples from patients, in whom the state
      of systemic T-cell responses against tumor-associated antigens (TAA) and Treg
      infiltration had previously been determined. RESULTS: All specimens contained
      cells positive for CD68, CD163, S100 and CD1a in epithelial tumor tissue and
      tumor stroma. Only a very few (less than median 3/HPF) CD123+, CD1a+, CD11c+, CD
      208+, CD209+, or Langerin+ cells were detected in the specimens. Overall, we
      found a trend towards increased infiltration by S100-positive DC and a
      significantly increased number of stromal S100-positive DC in patients without T
      cell response. There was an increase of stromal S100 DC and CD163 macrophages in
      limited disease (S100: 11.1/HPF vs. 7.3/HPF, p = 0.046; CD163: 11.0/HPF vs.
      8.1/HPF, p = 0.06). We found a significant, positive correlation between S100
      positive DC and FOXP3-positive Tregs. Survival in patients with high DC
      infiltration was significantly better than that in those with low DC infiltration
      (p < 0.05). Furthermore, we found a trend towards better survival for increased
      infiltration with CD163-positive macrophages (p = 0.07). CONCLUSION: The present
      in situ study adds new data to the discussion on the interaction between the
      innate and adoptive immune system. Our data strongly support the hypothesis that
      tumor-infiltrating DC are a key factor at the interface between innate and
      adaptive immune response in malignant disease. Tumor infiltrating S100-positive
      DC show an inverse relationship with the systemic antigen-specific T-cell
      response, a positive correlation with regulatory T cells, and a positive
      association with survival in CRC. These data put tumor-infiltrating DC at the
      center of the relevant immune response in CRC.

PMID- 18047663
TI  - SAT, a flexible and optimized Web application for SSR marker development.
AB  - BACKGROUND: Simple Sequence Repeats (SSRs), or microsatellites, are among the
      most powerful genetic markers known. A common method for the development of SSR
      markers is the construction of genomic DNA libraries enriched for SSR sequences,
      followed by DNA sequencing. However, designing optimal SSR markers from bulk
      sequence data is a laborious and time-consuming process. RESULTS: SAT (SSR
      Analysis Tool) is a user-friendly Web application developed to minimize tedious
      manual operations and reduce errors. This tool facilitates the integration,
      analysis and display of sequence data from SSR-enriched libraries.SAT is designed
      to successively perform base calling and quality evaluation of chromatograms,
      eliminate cloning vector, adaptors and low quality sequences, detect chimera or
      partially digested sequences, search for SSR motifs, cluster and assemble the
      redundant sequences, and design SSR primer pairs. An additional virtual PCR step
      establishes primer specificity. Users may modify the different parameters of each
      step of the SAT analysis. Although certain steps are compulsory, such as SSR
      motifs search and sequence assembly, users do not have to run the entire
      pipeline, and they can choose selectively which steps to perform. A database
      allows users to store and query results, and to redo individual steps of the
      workflow. CONCLUSION: The SAT Web application is available at
      http://sat.cirad.fr/sat, and a standalone command-line version is also freely
      downloadable. Users must send an email to the SAT administrator tropgene@cirad.fr
      to request a login and password.

PMID- 18047665
TI  - Assessing the evolutionary rate of positional orthologous genes in prokaryotes
      using synteny data.
AB  - BACKGROUND: Comparison of completely sequenced microbial genomes has revealed how
      fluid these genomes are. Detecting synteny blocks requires reliable methods to
      determining the orthologs among the whole set of homologs detected by exhaustive
      comparisons between each pair of completely sequenced genomes. This is a complex
      and difficult problem in the field of comparative genomics but will help to
      better understand the way prokaryotic genomes are evolving. RESULTS: We have
      developed a suite of programs that automate three essential steps to study
      conservation of gene order, and validated them with a set of 107 bacteria and
      archaea that cover the majority of the prokaryotic taxonomic space. We identified
      the whole set of shared homologs between two or more species and computed the
      evolutionary distance separating each pair of homologs. We applied two strategies
      to extract from the set of homologs a collection of valid orthologs shared by at
      least two genomes. The first computes the Reciprocal Smallest Distance (RSD)
      using the PAM distances separating pairs of homologs. The second method groups
      homologs in families and reconstructs each family's evolutionary tree,
      distinguishing bona fide orthologs as well as paralogs created after the last
      speciation event. Although the phylogenetic tree method often succeeds where RSD
      fails, the reverse could occasionally be true. Accordingly, we used the data
      obtained with either methods or their intersection to number the orthologs that
      are adjacent in for each pair of genomes, the Positional Orthologous Genes
      (POGs), and to further study their properties. Once all these synteny blocks have
      been detected, we showed that POGs are subject to more evolutionary constraints
      than orthologs outside synteny groups, whichever the taxonomic distance
      separating the compared organisms. CONCLUSION: The suite of programs described in
      this paper allows a reliable detection of orthologs and is useful for evaluating
      gene order conservation in prokaryotes whichever their taxonomic distance. Thus,
      our approach will make easy the rapid identification of POGS in the next few
      years as we are expecting to be inundated with thousands of completely sequenced
      microbial genomes.

PMID- 18047664
TI  - The oxidative stress adaptor p66Shc is required for permanent embryo arrest in
      vitro.
AB  - BACKGROUND: Excessive developmental failure occurs during the first week of in
      vitro embryo development due to elevated levels of cell death and arrest. We
      hypothesize that permanently arrested embryos enter a stress-induced "senescence
      like" state that is dependent on the oxidative stress-adaptor and lifespan
      determinant protein p66Shc. The aim of this study was to selectively diminish
      p66Shc gene expression in bovine oocytes and embryos using post-transcriptional
      gene silencing by RNA-mediated interference to study the effects of p66Shc
      knockdown on in vitro fertilized bovine embryos. RESULTS: Approximately 12,000
      24,000 short hairpin (sh)RNAi molecules specific for p66Shc were microinjected
      into bovine germinal vesicle stage oocytes or zygotes. Experiments were comprised
      of a control group undergoing IVF alone and two groups microinjected with and
      without p66Shc shRNAi molecules prior to IVF. The amount of p66Shc mRNA
      quantified by Real Time PCR was significantly (P < 0.001) lowered upon p66Shc
      shRNAi microinjection. This reduction was selective for p66Shc mRNA, as both
      histone H2a and p53 mRNA levels were not altered. The relative signal strength of
      p66Shc immuno-fluorescence revealed a significant reduction in the number of
      pixels for p66Shc shRNAi microinjected groups compared to controls (P < 0.05). A
      significant decrease (P < 0.001) in the incidence of arrested embryos upon p66Shc
      shRNAi microinjection was detected compared to IVF and microinjected controls
      along with significant reductions (P < 0.001) in both cleavage divisions and
      blastocyst development. No significant differences in p66Shc mRNA levels (P =
      0.314) were observed among the three groups at the blastocyst stage. CONCLUSION:
      These results show that p66Shc is involved in the regulation of embryo
      development specifically in mediating early cleavage arrest and facilitating
      development to the blastocyst stage for in vitro produced bovine embryos.

PMID- 18047666
TI  - Decoupling of arsenic and iron release from ferrihydrite suspension under
      reducing conditions: a biogeochemical model.
AB  - High levels of arsenic in groundwater and drinking water are a major health
      problem. Although the processes controlling the release of As are still not well
      known, the reductive dissolution of As-rich Fe oxyhydroxides has so far been a
      favorite hypothesis. Decoupling between arsenic and iron redox transformations
      has been experimentally demonstrated, but not quantitatively interpreted. Here,
      we report on incubation batch experiments run with As(V) sorbed on, or co
      precipitated with, 2-line ferrihydrite. The biotic and abiotic processes of As
      release were investigated by using wet chemistry, X-ray diffraction, X-ray
      absorption and genomic techniques. The incubation experiments were carried out
      with a phosphate-rich growth medium and a community of Fe(III)-reducing bacteria
      under strict anoxic conditions for two months. During the first month, the
      release of Fe(II) in the aqueous phase amounted to only 3% to 10% of the total
      initial solid Fe concentration, whilst the total aqueous As remained almost
      constant after an initial exchange with phosphate ions. During the second month,
      the aqueous Fe(II) concentration remained constant, or even decreased, whereas
      the total quantity of As released to the solution accounted for 14% to 45% of the
      total initial solid As concentration. At the end of the incubation, the aqueous
      phase arsenic was present predominately as As(III) whilst X-ray absorption
      spectroscopy indicated that more than 70% of the solid-phase arsenic was present
      as As(V). X-ray diffraction revealed vivianite Fe(II)3(PO4)2.8H2O in some of the
      experiments. A biogeochemical model was then developed to simulate these aqueous-
      and solid-phase results. The two main conclusions drawn from the model are that
      (1) As(V) is not reduced during the first incubation month with high Eh values,
      but rather re-adsorbed onto the ferrihydrite surface, and this state remains
      until arsenic reduction is energetically more favorable than iron reduction, and
      (2) the release of As during the second month is due to its reduction to the more
      weakly adsorbed As(III) which cannot compete against carbonate ions for sorption
      onto ferrihydrite. The model was also successfully applied to recent experimental
      results on the release of arsenic from Bengal delta sediments.

PMID- 18047667
TI  - Codon-triplet context unveils unique features of the Candida albicans protein
      coding genome.
AB  - BACKGROUND: The evolutionary forces that determine the arrangement of synonymous
      codons within open reading frames and fine tune mRNA translation efficiency are
      not yet understood. In order to tackle this question we have carried out a large
      scale study of codon-triplet contexts in 11 fungal species to unravel
      associations or relationships between codons present at the ribosome A-, P- and E
      sites during each decoding cycle. RESULTS: Our analysis unveiled high bias within
      the context of codon-triplets, in particular strong preference for triplets of
      identical codons. We have also identified a surprisingly large number of codon
      triplet combinations that vanished from fungal ORFeomes. Candida albicans
      exacerbated these features, showed an unbalanced tRNA population for decoding its
      pool of codons and used near-cognate decoding for a large set of codons,
      suggesting that unique evolutionary forces shaped the evolution of its ORFeome.
      CONCLUSION: We have developed bioinformatics tools for large-scale analysis of
      codon-triplet contexts. These algorithms identified codon-triplets context
      biases, allowed for large scale comparative codon-triplet analysis, and
      identified rules governing codon-triplet context. They could also detect
      alterations to the standard genetic code.

PMID- 18047668
TI  - Selecting process quality indicators for the integrated care of vulnerable older
      adults affected by cognitive impairment or dementia.
AB  - BACKGROUND: This study aimed at evaluating face and content validity, feasibility
      and reliability of process quality indicators developed previously in the United
      States or other countries. The indicators can be used to evaluate care and
      services for vulnerable older adults affected by cognitive impairment or dementia
      within an integrated service system in Quebec, Canada. METHODS: A total of 33
      clinical experts from three major urban centres in Quebec formed a panel
      representing two medical specialties (family medicine, geriatrics) and seven
      health or social services specialties (nursing, occupational therapy, psychology,
      neuropsychology, pharmacy, nutrition, social work), from primary or secondary
      levels of care, including long-term care. A modified version of the
      RAND(R)/University of California at Los Angeles (UCLA) appropriateness method, a
      two-round Delphi panel, was used to assess face and content validity of process
      quality indicators. The appropriateness of indicators was evaluated according to
      a) agreement of the panel with three criteria, defined as a median rating of 7-9
      on a nine-point rating scale, and b) agreement among panellists, judged by the
      statistical measure of the interpercentile range adjusted for symmetry.
      Feasibility of quality assessment and reliability of appropriate indicators were
      then evaluated within a pilot study on 29 patients affected by cognitive
      impairment or dementia. For measurable indicators the inter-observer reliability
      was calculated with the Kappa statistic. RESULTS: Initially, 82 indicators for
      care of vulnerable older adults with cognitive impairment or dementia were
      submitted to the panellists. Of those, 72 (88%) were accepted after two rounds.
      Among 29 patients for whom medical files of the preceding two years were
      evaluated, 63 (88%) of these indicators were considered applicable at least once,
      for at least one patient. Only 22 indicators were considered applicable at least
      once for ten or more out of 29 patients. Four indicators could be measured with
      the help of a validated questionnaire on patient satisfaction. Inter-observer
      reliability was moderate (Kappa = 0.57). CONCLUSION: A multidisciplinary panel of
      experts judged a large majority of the initial indicators valid for use in
      integrated care systems for vulnerable older adults in Quebec, Canada. Most of
      these indicators can be measured using patient files or patient or caregiver
      interviews and reliability of assessment from patient-files is moderate.

PMID- 18047669
TI  - Evolutionary conservation of plant gibberellin signalling pathway components.
AB  - BACKGROUND: Gibberellins (GA) are plant hormones that can regulate germination,
      elongation growth, and sex determination. They ubiquitously occur in seed plants.
      The discovery of gibberellin receptors, together with advances in understanding
      the function of key components of GA signalling in Arabidopsis and rice, reveal a
      fairly short GA signal transduction route. The pathway essentially consists of
      GID1 gibberellin receptors that interact with F-box proteins, which in turn
      regulate degradation of downstream DELLA proteins, suppressors of GA-controlled
      responses. RESULTS: Arabidopsis sequences of the gibberellin signalling compounds
      were used to screen databases from a variety of plants, including protists, for
      homologues, providing indications for the degree of conservation of the pathway.
      The pathway as such appears completely absent in protists, the moss
      Physcomitrella patens shares only a limited homology with the Arabidopsis
      proteins, thus lacking essential characteristics of the classical GA signalling
      pathway, while the lycophyte Selaginella moellendorffii contains a possible
      ortholog for each component. The occurrence of classical GA responses can as yet
      not be linked with the presence of homologues of the signalling pathway.
      Alignments and display in neighbour joining trees of the GA signalling components
      confirm the close relationship of gymnosperms, monocotyledonous and
      dicotyledonous plants, as suggested from previous studies. CONCLUSION: Homologues
      of the GA-signalling pathway were mainly found in vascular plants. The GA
      signalling system may have its evolutionary molecular onset in Physcomitrella
      patens, where GAs at higher concentrations affect gravitropism and elongation
      growth.

PMID- 18047670
TI  - Small steps or giant leaps for male-killers? Phylogenetic constraints to male
      killer host shifts.
AB  - BACKGROUND: Arthropods are infected by a wide diversity of maternally transmitted
      microbes. Some of these manipulate host reproduction to facilitate population
      invasion and persistence. Such parasites transmit vertically on an ecological
      timescale, but rare horizontal transmission events have permitted colonisation of
      new species. Here we report the first systematic investigation into the influence
      of the phylogenetic distance between arthropod species on the potential for
      reproductive parasite interspecific transfer. RESULTS: We employed a well
      characterised reproductive parasite, a coccinellid beetle male-killer, and
      artificially injected the bacterium into a series of novel species. Genetic
      distances between native and novel hosts were ascertained by sequencing sections
      of the 16S and 12S mitochondrial rDNA genes. The bacterium colonised host tissues
      and transmitted vertically in all cases tested. However, whilst transmission
      efficiency was perfect within the native genus, this was reduced following some
      transfers of greater phylogenetic distance. The bacterium's ability to distort
      offspring sex ratios in novel hosts was negatively correlated with the genetic
      distance of transfers. Male-killing occurred with full penetrance following
      within-genus transfers; but whilst sex ratio distortion generally occurred, it
      was incomplete in more distantly related species. CONCLUSION: This study
      indicates that the natural interspecific transmission of reproductive parasites
      might be constrained by their ability to tolerate the physiology or genetics of
      novel hosts. Our data suggest that horizontal transfers are more likely between
      closely related species. Successful bacterial transfer across large phylogenetic
      distances may require rapid adaptive evolution in the new species. This finding
      has applied relevance regarding selection of suitable bacteria to manipulate
      insect pest and vector populations by symbiont gene-drive systems.

PMID- 18047671
TI  - Lymphatic vessel density and function in experimental bladder cancer.
AB  - BACKGROUND: The lymphatics form a second circulatory system that drains the
      extracellular fluid and proteins from the tumor microenvironment, and provides an
      exclusive environment in which immune cells interact and respond to foreign
      antigen. Both cancer and inflammation are known to induce lymphangiogenesis.
      However, little is known about bladder lymphatic vessels and their involvement in
      cancer formation and progression. METHODS: A double transgenic mouse model was
      generated by crossing a bladder cancer-induced transgenic, in which SV40 large T
      antigen was under the control of uroplakin II promoter, with another transgenic
      mouse harboring a lacZ reporter gene under the control of an NF-kappaB-responsive
      promoter (kappaB-lacZ) exhibiting constitutive activity of beta-galactosidase in
      lymphatic endothelial cells. In this new mouse model (SV40-lacZ), we examined the
      lymphatic vessel density (LVD) and function (LVF) during bladder cancer
      progression. LVD was performed in bladder whole mounts and cross-sections by
      fluorescent immunohistochemistry (IHC) using LYVE-1 antibody. LVF was assessed by
      real-time in vivo imaging techniques using a contrast agent (biotin-BSA-Gd-DTPA
      Cy5.5; Gd-Cy5.5) suitable for both magnetic resonance imaging (MRI) and near
      infrared fluorescence (NIRF). In addition, IHC of Cy5.5 was used for time-course
      analysis of co-localization of Gd-Cy5.5 with LYVE-1-positive lymphatics and CD31
      positive blood vessels. RESULTS: SV40-lacZ mice develop bladder cancer and
      permitted visualization of lymphatics. A significant increase in LVD was found
      concomitantly with bladder cancer progression. Double labeling of the bladder
      cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced
      lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and
      permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a
      contrast agent for MRI-guided lymphangiography, we determined a possible
      reduction of lymphatic flow within the tumoral area. In addition, NIRF studies of
      Gd-Cy5.5 confirmed its temporal distribution between CD31-positive blood vessels
      and LYVE-1 positive lymphatic vessels. CONCLUSION: SV40-lacZ mice permit the
      visualization of lymphatics during bladder cancer progression. Gd-Cy5.5, as a
      double contrast agent for NIRF and MRI, permits to quantify delivery, transport
      rates, and volumes of macromolecular fluid flow through the interstitial
      lymphatic continuum. Our results open the path for the study of lymphatic
      activity in vivo and in real time, and support the role of lymphangiogenesis
      during bladder cancer progression.

PMID- 18047672
TI  - Functional, genetic and bioinformatic characterization of a calcium/calmodulin
      kinase gene in Sporothrix schenckii.
AB  - BACKGROUND: Sporothrix schenckii is a pathogenic, dimorphic fungus, the
      etiological agent of sporotrichosis, a subcutaneous lymphatic mycosis. Dimorphism
      in S. schenckii responds to second messengers such as cAMP and calcium,
      suggesting the possible involvement of a calcium/calmodulin kinase in its
      regulation. In this study we describe a novel calcium/calmodulin-dependent
      protein kinase gene in S. schenckii, sscmk1, and the effects of inhibitors of
      calmodulin and calcium/calmodulin kinases on the yeast to mycelium transition and
      the yeast cell cycle. RESULTS: Using the PCR homology approach a new member of
      the calcium/calmodulin kinase family, SSCMK1, was identified in this fungus. The
      cDNA sequence of sscmk1 revealed an open reading frame of 1,221 nucleotides
      encoding a 407 amino acid protein with a predicted molecular weight of 45.6 kDa.
      The genomic sequence of sscmk1 revealed the same ORF interrupted by five introns.
      Bioinformatic analyses of SSCMK1 showed that this protein had the distinctive
      features that characterize a calcium/calmodulin protein kinase: a
      serine/threonine protein kinase domain and a calmodulin-binding domain. When
      compared to homologues from seven species of filamentous fungi, SSCMK1 showed
      substantial similarities, except for a large and highly variable region that
      encompasses positions 330 - 380 of the multiple sequence alignment. Inhibition
      studies using calmodulin inhibitor W-7, and calcium/calmodulin kinase inhibitors,
      KN-62 and lavendustin C, were found to inhibit budding by cells induced to re
      enter the yeast cell cycle and to favor the yeast to mycelium transition.
      CONCLUSION: This study constitutes the first evidence of the presence of a
      calcium/calmodulin kinase-encoding gene in S. schenckii and its possible
      involvement as an effector of dimorphism in this fungus. These results suggest
      that a calcium/calmodulin dependent signaling pathway could be involved in the
      regulation of dimorphism in this fungus. The results suggest that the
      calcium/calmodulin kinases of yeasts are evolutionarily distinct from those in
      filamentous fungi.

PMID- 18047673
TI  - Contributions of different mosquito species to the transmission of lymphatic
      filariasis in central Nigeria: implications for monitoring infection by PCR in
      mosquito pools.
AB  - BACKGROUND: Members of the Anopheles gambiae complex are important vectors of
      lymphatic filariasis (LF) in sub-Saharan Africa, but little is known about the
      relative contributions of all mosquitoes to lymphatic filariasis transmission in
      this area. METHODS: Over a 28 month period, mosquitoes were collected from 13
      villages in Plateau and Nasarawa states in central Nigeria and dissected to
      determine W. bancrofti infection status. Wings and legs from a subset of the
      mosquitoes visually identified as A. gambiae s.l. were identified by PCR as
      either A. gambiae s.s. or A. arabiensis. RESULTS: A. gambiae s.s peaked in
      abundance during the rainy season while A. arabiensis predominated during drier
      parts of the year. Both species were found equally likely to be infected with the
      developing stages (L1-L3) of W. bancrofti (9.2% and 11.1%, respectively). Fewer
      A. funestus (1.1%, p < 0.001) were infected than A. gambiae s.l. CONCLUSION:
      Understanding the relative contributions of morphologically indistinguishable
      species to LF transmission is essential if PCR is to be performed on mosquito
      pools. In the study area, the use of mosquito pools composed of A. gambiae
      sibling species would not be problematic, as both A. gambiae s.s. and A.
      arabiensis contribute equally to LF transmission.

PMID- 18047674
TI  - Identification of candidate predictive and surrogate molecular markers for
      dasatinib in prostate cancer: rationale for patient selection and efficacy
      monitoring.
AB  - BACKGROUND: Dasatinib is a potent, multi-targeted kinase inhibitor that was
      recently approved for treatment of chronic myelogenous leukemia resistant to
      imatinib. To aid the clinical development of dasatinib in prostate cancer, we
      utilized preclinical models to identify potential molecular markers for patient
      stratification and efficacy monitoring. RESULTS: Using gene expression profiling,
      we first identified 174 genes whose expression was highly correlated with in
      vitro sensitivity of 16 cell lines and, thus, considered as candidate efficacy
      predictive markers. Among these are important prostatic cell lineage markers,
      cytokeratin 5, androgen receptor and prostate specific antigen. Our results
      indicate that 'basal type' cell lines with high expression of cytokeratin 5 and
      low expression of androgen receptor or prostate specific antigen are sensitive to
      dasatinib. To identify markers as surrogates for biological activity, we treated
      cell lines with dasatinib and identified genes whose expression was significantly
      modulated by the drug. Ten genes, including that encoding urokinase-type
      plasminogen activator (uPA), were found to not only be potential efficacy markers
      but also to have reduced expression upon dasatinib treatment. The down-regulation
      of uPA by dasatinib was drug-specific and correlated with the sensitivity of cell
      lines to dasatinib. Furthermore, EphA2, a target of dasatinib, was found to be a
      sensitivity biomarker. CONCLUSION: Using the gene expression profiling approach
      and preclinical models, we have identified prostatic biomarkers that are
      associated with sensitivity to dasatinib. This study has provided a basis for
      clinical evaluation of a potential dasatinib efficacy signature in prostate
      cancer.

PMID- 18047675
TI  - Computational prediction and experimental validation of Ciona intestinalis
      microRNA genes.
AB  - BACKGROUND: This study reports the first collection of validated microRNA genes
      in the sea squirt, Ciona intestinalis. MicroRNAs are processed from hairpin
      precursors to ~22 nucleotide RNAs that base pair to target mRNAs and inhibit
      expression. As a member of the subphylum Urochordata (Tunicata) whose larval form
      has a notochord, the sea squirt is situated at the emergence of vertebrates, and
      therefore may provide information about the evolution of molecular regulators of
      early development. RESULTS: In this study, computational methods were used to
      predict 14 microRNA gene families in Ciona intestinalis. The microRNA prediction
      algorithm utilizes configurable microRNA sequence conservation and stem-loop
      specificity parameters, grouping by miRNA family, and phylogenetic conservation
      to the related species, Ciona savignyi. The expression for 8, out of 9 attempted,
      of the putative microRNAs in the adult tissue of Ciona intestinalis was validated
      by Northern blot analyses. Additionally, a target prediction algorithm was
      implemented, which identified a high confidence list of 240 potential target
      genes. Over half of the predicted targets can be grouped into the gene ontology
      categories of metabolism, transport, regulation of transcription, and cell
      signaling. CONCLUSION: The computational techniques implemented in this study can
      be applied to other organisms and serve to increase the understanding of the
      origins of non-coding RNAs, embryological and cellular developmental pathways,
      and the mechanisms for microRNA-controlled gene regulatory networks.

PMID- 18047676
TI  - Esophageal cancer in a young woman with bulimia nervosa: a case report.
AB  - Adenocarcinoma of the esophagus has increased dramatically within the United
      States and continues to have a poor prognosis despite aggressive treatment.
      Identifying potential risk factors is critical for the early detection and
      treatment of this disease. The present case report describes a very young woman
      who developed adenocarcinoma of the esophagus after only a brief history of
      bulimia. These findings suggest that even in very young patients, bulimia may
      represent a risk factor for adenocarcinoma of the esophagus.

PMID- 18047677
TI  - Immunolocalisation of phosphorylated STAT3, interleukin 11 and leukaemia
      inhibitory factor in endometrium of women with unexplained infertility during the
      implantation window.
AB  - BACKGROUND: Uterine receptivity and embryo implantation are critical in the
      establishment of pregnancy. The diagnosis of endometrial fertility requires more
      precise measurements of endometrial receptivity. Interleukin (IL-11) and leukemia
      inhibitory factor (LIF) are essential for murine implantation and signal via
      intracellular phosphorylation (p) of STAT3 in the endometrium. Both cytokines are
      present in the endometrium of women duiring the receptive window. Endometrial IL
      11, IL-11 receptor alpha (IL-11Ralpha), LIF and pSTAT3 in women with primary
      unexplained infertility was compared to normal fertile women during the
      implantation window. METHODS: LH timed endometrial biopsies (LH+6 to LH+10) were
      collected from women with unexplained infertility and normal fertility. pSTAT3,
      IL-11, IL-11Ralpha and LIF production was determined by immunohistochemistry.
      Staining intensity was determoned by two independent observers blind to the
      fertility status of the patient from whom the biopsy was taken. Staining
      intensity and heterogeneity in each of the endometrial compartments (epithelium;
      stroma, including decidualized stromal cells; and vasculature) was assessed. The
      Mann-Whitney U test was used to analyze IL-11, pSTAT3, IL-11Ralpha and LIF
      immunostaining intensities in the samples. RESULTS: IL-11, IL-11Ralpha and LIF
      were present predominantly in glandular epithelium, whilst luminal epithelium
      showed patchy staining. pSTAT3 was present in both glandular epithelium and
      stroma. IL-11 and pSTAT3 immunostaining was significantly lower in glandular
      epithelium in infertile women compared to controls (P < 0.05) whilst IL-11Ralpha
      and LIF staining did not differ. CONCLUSION: This is the first demonstration of
      reduced endometrial pSTAT3 and IL-11 in some women with unexplained infertility.
      This suggests IL-11 and pSTAT3 may be involved in the secretory transformation of
      glandular epithelium during receptivity. Reduced IL-11 production and STAT3
      phosphorylation may contribute to unexplained infertility in some women.

PMID- 18047678
TI  - Improving quality of reproductive health care in Senegal through formative
      supervision: results from four districts.
AB  - BACKGROUND: In Senegal, traditional supervision often focuses more on collection
      of service statistics than on evaluation of service quality. This approach yields
      limited information on quality of care and does little to improve providers'
      competence. In response to this challenge, Management Sciences for Health (MSH)
      has implemented a program of formative supervision. This multifaceted, problem
      solving approach collects data on quality of care, improves technical competence,
      and engages the community in improving reproductive health care. METHODS: This
      study evaluated changes in service quality and community involvement after two
      rounds of supervision in 45 health facilities in four districts of Senegal. We
      used checklists to assess quality in four areas of service delivery:
      infrastructure, staff and services management, record-keeping, and technical
      competence. We also measured community involvement in improving service quality
      using the completion rates of action plans. RESULTS: The most notable improvement
      across regions was in infection prevention.Management of staff, services, and
      logistics also consistently improved across the four districts. Record-keeping
      skills showed variable but lower improvement by region. The completion rates of
      action plans suggest that communities are engaged in improving service quality in
      all four districts. CONCLUSION: Formative supervision can improve the quality of
      reproductive health services, especially in areas where there is on-site skill
      building and refresher training. This approach can also mobilize communities to
      participate in improving service quality.

PMID- 18047679
TI  - Subcellular location prediction of proteins using support vector machines with
      alignment of block sequences utilizing amino acid composition.
AB  - BACKGROUND: Subcellular location prediction of proteins is an important and well
      studied problem in bioinformatics. This is a problem of predicting which part in
      a cell a given protein is transported to, where an amino acid sequence of the
      protein is given as an input. This problem is becoming more important since
      information on subcellular location is helpful for annotation of proteins and
      genes and the number of complete genomes is rapidly increasing. Since existing
      predictors are based on various heuristics, it is important to develop a simple
      method with high prediction accuracies. RESULTS: In this paper, we propose a
      novel and general predicting method by combining techniques for sequence
      alignment and feature vectors based on amino acid composition. We implemented
      this method with support vector machines on plant data sets extracted from the
      TargetP database. Through fivefold cross validation tests, the obtained overall
      accuracies and average MCC were 0.9096 and 0.8655 respectively. We also applied
      our method to other datasets including that of WoLF PSORT. CONCLUSION: Although
      there is a predictor which uses the information of gene ontology and yields
      higher accuracy than ours, our accuracies are higher than existing predictors
      which use only sequence information. Since such information as gene ontology can
      be obtained only for known proteins, our predictor is considered to be useful for
      subcellular location prediction of newly-discovered proteins. Furthermore, the
      idea of combination of alignment and amino acid frequency is novel and general so
      that it may be applied to other problems in bioinformatics. Our method for plant
      is also implemented as a web-system and available on http://sunflower.kuicr.kyoto
      u.ac.jp/~tamura/slpfa.html.

PMID- 18047680
TI  - Synthesis of the benzo-fused indolizidine alkaloid mimics.
AB  - A general synthesis of various benzo-fused indolizidine alkaloid mimics has been
      developed. The indolizidine derivatives 8 were prepared via heteroaryl Grignard
      addition to N-acylpyridinium salts followed by an intramolecular Heck
      cyclization. Further substitution reactions were developed to demonstrate that
      heterocycles 8 are good scaffolds for chemical library preparation.

PMID- 18047681
TI  - Comparison of effectiveness of Halo-femoral traction after anterior spinal
      release in severe idiopathic and congenital scoliosis: a retrospective study.
AB  - BACKGROUND: Halo-femoral traction could gradually improve the coronal and
      sagittal deformity and restore the trunk balance through the elongation of the
      spine. The purpose of this retrospective study was to assess the effectiveness of
      Halo-femoral traction after anterior spinal release in the management of severe
      idiopathic and congenital scoliosis. METHODS: Sixty patients with severe and
      rigid curve treated with anterior spinal release, Halo-femoral traction, and
      second stage posterior spinal fusion were recruited for this retrospective study.
      Idiopathic Scoliosis (IS) group was 30 patients (23 females and 7 males) with
      mean age of 15.5 years. The average coronal Cobb angle was 91.6 degrees and the
      mean global thoracic kyphosis was 50.6 degrees . The curve type of these patients
      were 2 with Lenke 1AN, 4 with Lenke 1A+, 1 with Lenke 1BN, 10 with Lenke 1CN, 3
      with Lenke 1C+, 3 with Lenke 3CN, 3 with Lenke 3C+, and 4 with Lenke 5C+.
      Congenital Scoliosis (CS) group included 30 patients (20 females and 10 males)
      with average age of 15.2 years. The average coronal Cobb angle of the main curve
      before operation was 95.7 degrees and the average thoracic kyphosis was 70.2
      degrees . All patients had a minimum 12-month follow-up radiograph (range 12-72
      months, mean 38 months). RESULTS: The average traction time was 23 days and the
      average traction weight was 16 kg. Four patients experienced brachial plexus
      palsy and complete nerve functional restoration was achieved at two months follow
      up. For the IS group, the post-operative mean Cobb angle of major curve averaged
      40.1 degrees with correction rate of 57.5%. For the CS group, the post-operative
      mean Cobb angle was 56.5 degrees with average correction rate of 45.2%. The
      difference in curve magnitude between the IS and CS patients after posterior
      correction was statistically significant (t = 4.15, p < 0.001). The correction
      rate of kyphosis between IS and CS patients was also statistically significant (t
      = -2.59, p < 0.016). CONCLUSION: Halo-femoral traction was a safe, well-tolerated
      and effective method for the treatment of severe and rigid scoliosis patients.
      The posterior correction rate obtained after anterior release and traction was
      significant superior than that recorded from side bending film in current study.

PMID- 18047682
TI  - Double knockdown of alpha1,6-fucosyltransferase (FUT8) and GDP-mannose 4,6
      dehydratase (GMD) in antibody-producing cells: a new strategy for generating
      fully non-fucosylated therapeutic antibodies with enhanced ADCC.
AB  - BACKGROUND: Antibody-dependent cellular cytotoxicity (ADCC) is greatly enhanced
      by the absence of the core fucose of oligosaccharides attached to the Fc, and is
      closely related to the clinical efficacy of anticancer activity in humans in
      vivo. Unfortunately, all licensed therapeutic antibodies and almost all currently
      developed therapeutic antibodies are heavily fucosylated and fail to optimize
      ADCC, which leads to a large dose requirement at a very high cost for the
      administration of antibody therapy to cancer patients. In this study, we explored
      the possibility of converting already-established antibody-producing cells to
      cells that produce antibodies fully lacking core fucosylation in order to
      facilitate the rapid development of next-generation therapeutic antibodies.
      RESULTS: Firstly, loss-of-function analyses using small interfering RNAs (siRNAs)
      against the three key genes involved in oligosaccharide fucose modification, i.e.
      alpha1,6-fucosyltransferase (FUT8), GDP-mannose 4,6-dehydratase (GMD), and GDP
      fucose transporter (GFT), revealed that single-gene knockdown of each target was
      insufficient to completely defucosylate the products in antibody-producing cells,
      even though the most effective siRNA (>90% depression of the target mRNA) was
      employed. Interestingly, beyond our expectations, synergistic effects of FUT8 and
      GMD siRNAs on the reduction in fucosylation were observed, but not when these
      were used in combination with GFT siRNA. Secondly, we successfully developed an
      effective short hairpin siRNA tandem expression vector that facilitated the
      double knockdown of FUT8 and GMD, and we converted antibody-producing Chinese
      hamster ovary (CHO) cells to fully non-fucosylated antibody producers within two
      months, and with high converting frequency. Finally, the stable manufacture of
      fully non-fucosylated antibodies with enhanced ADCC was confirmed using the
      converted cells in serum-free fed-batch culture. CONCLUSION: Our results suggest
      that FUT8 and GMD collaborate synergistically in the process of intracellular
      oligosaccharide fucosylation. We also demonstrated that double knockdown of FUT8
      and GMD in antibody-producing cells could serve as a new strategy for producing
      next-generation therapeutic antibodies fully lacking core fucosylation and with
      enhanced ADCC. This approach offers tremendous cost- and time-sparing advantages
      for the development of next-generation therapeutic antibodies.

PMID- 18047683
TI  - Bacterial flora-typing with targeted, chip-based Pyrosequencing.
AB  - BACKGROUND: The metagenomic analysis of microbial communities holds the potential
      to improve our understanding of the role of microbes in clinical conditions.
      Recent, dramatic improvements in DNA sequencing throughput and cost will enable
      such analyses on individuals. However, such advances in throughput generally come
      at the cost of shorter read-lengths, limiting the discriminatory power of each
      read. In particular, classifying the microbial content of samples by sequencing
      the < 1,600 bp 16S rRNA gene will be affected by such limitations. RESULTS: We
      describe a method for identifying the phylogenetic content of bacterial samples
      using high-throughput Pyrosequencing targeted at the 16S rRNA gene. Our analysis
      is adapted to the shorter read-lengths of such technology and uses a database of
      16S rDNA to determine the most specific phylogenetic classification for reads,
      resulting in a weighted phylogenetic tree characterizing the content of the
      sample. We present results for six samples obtained from the human vagina during
      pregnancy that corroborates previous studies using conventional techniques.Next,
      we analyze the power of our method to classify reads at each level of the
      phylogeny using simulation experiments. We assess the impacts of read-length and
      database completeness on our method, and predict how we do as technology improves
      and more bacteria are sequenced. Finally, we study the utility of targeting
      specific 16S variable regions and show that such an approach considerably
      improves results for certain types of microbial samples. Using simulation, our
      method can be used to determine the most informative variable region. CONCLUSION:
      This study provides positive validation of the effectiveness of targeting 16S
      metagenomes using short-read sequencing technology. Our methodology allows us to
      infer the most specific assignment of the sequence reads within the phylogeny,
      and to identify the most discriminative variable region to target. The analysis
      of high-throughput Pyrosequencing on human flora samples will accelerate the
      study of the relationship between the microbial world and ourselves.

PMID- 18047684
TI  - Epigenetic regulation of RhoB loss of expression in lung cancer.
AB  - BACKGROUND: RhoB is down-regulated in most lung cancer cell lines and tumor
      tissues when compared with their normal counterparts. The mechanism of this loss
      of expression is not yet deciphered. METHODS: Since no mutation has been reported
      in the RhoB sequence, we investigated the epigenetic regulation of RhoB
      expression by analyzing the effect of HDAC inhibitors and methyltransferase
      inhibitors, by direct sequencing after bisulfite treatment and by methylation
      specific PCR. RESULTS: We first showed that histone deacetylase (HDAC) inhibitors
      induce a significant RhoB re-expression in lung cancer cell lines whereas only a
      slight effect was observed with methyl transferase inhibitors. As promoter
      methylation is the most common epigenetic process in lung cancer, we performed
      methylation specific PCR and sequence analysis after bisulfite treatment and
      demonstrated that RhoB was methylated neither in lung cancer cell lines nor in
      tumor tissues. We also showed that a variable number of tandem repeats sequences
      in the 5' region of the RhoB gene was involved in HDAC response. CONCLUSION: We
      thus propose that RhoB regulation of expression occurs mainly by histone
      deacetylation rather than by promoter hypermethylation and that this process can
      be modulated by specific 5' sequences within the promoter.

PMID- 18047685
TI  - Influenza activity in Europe during eight seasons (1999-2007): an evaluation of
      the indicators used to measure activity and an assessment of the timing, length
      and course of peak activity (spread) across Europe.
AB  - BACKGROUND: The European Influenza Surveillance Scheme (EISS) has collected
      clinical and virological data on influenza since 1996 in an increasing number of
      countries. The EISS dataset was used to characterise important epidemiological
      features of influenza activity in Europe during eight winters (1999-2007). The
      following questions were addressed: 1) are the sentinel clinical reports a good
      measure of influenza activity? 2) how long is a typical influenza season in
      Europe? 3) is there a west-east and/or south-north course of peak activity
      ('spread') of influenza in Europe? METHODS: Influenza activity was measured by
      collecting data from sentinel general practitioners (GPs) and reports by national
      reference laboratories. The sentinel reports were first evaluated by comparing
      them to the laboratory reports and were then used to assess the timing and spread
      of influenza activity across Europe during eight seasons. RESULTS: We found a
      good match between the clinical sentinel data and laboratory reports of influenza
      collected by sentinel physicians (overall match of 72% for +/- 1 week
      difference). We also found a moderate to good match between the clinical sentinel
      data and laboratory reports of influenza from non-sentinel sources (overall match
      of 60% for +/- 1 week). There were no statistically significant differences
      between countries using ILI (influenza-like illness) or ARI (acute respiratory
      disease) as case definition. When looking at the peak-weeks of clinical activity,
      the average length of an influenza season in Europe was 15.6 weeks (median 15
      weeks; range 12-19 weeks). Plotting the peak weeks of clinical influenza activity
      reported by sentinel GPs against the longitude or latitude of each country
      indicated that there was a west-east spread of peak activity (spread) of
      influenza across Europe in four winters (2001-2002, 2002-2003, 2003-2004 and 2004
      2005) and a south-north spread in three winters (2001-2002, 2004-2005 and 2006
      2007). CONCLUSION: We found that: 1) the clinical data reported by sentinel
      physicians is a valid indicator of influenza activity; 2) the length of influenza
      activity across the whole of Europe was surprisingly long, ranging from 12-19
      weeks; 3) in 4 out of the 8 seasons, there was a west-east spread of influenza,
      in 3 seasons a south-north spread; not associated with type of dominant virus in
      those seasons.

PMID- 18047686
TI  - Technology transfer from worms and flies to vertebrates: transposition-based
      genome manipulations and their future perspectives.
AB  - To meet the increasing demand of linking sequence information to gene function in
      vertebrate models, genetic modifications must be introduced and their effects
      analyzed in an easy, controlled, and scalable manner. In the mouse, only about
      10% (estimate) of all genes have been knocked out, despite continuous
      methodologic improvement and extensive effort. Moreover, a large proportion of
      inactivated genes exhibit no obvious phenotypic alterations. Thus, in order to
      facilitate analysis of gene function, new genetic tools and strategies are
      currently under development in these model organisms. Loss of function and gain
      of function mutagenesis screens based on transposable elements have numerous
      advantages because they can be applied in vivo and are therefore phenotype
      driven, and molecular analysis of the mutations is straightforward. At present,
      laboratory harnessing of transposable elements is more extensive in invertebrate
      models, mostly because of their earlier discovery in these organisms. Transposons
      have already been found to facilitate functional genetics research greatly in
      lower metazoan models, and have been applied most comprehensively in Drosophila.
      However, transposon based genetic strategies were recently established in
      vertebrates, and current progress in this field indicates that transposable
      elements will indeed serve as indispensable tools in the genetic toolkit for
      vertebrate models. In this review we provide an overview of transposon based
      genetic modification techniques used in higher and lower metazoan model
      organisms, and we highlight some of the important general considerations
      concerning genetic applications of transposon systems.

PMID- 18047687
TI  - Meganuclease and transposon mediated transgenesis in medaka.
AB  - From among a plethora of various gene delivery methods, the researcher must
      choose the right one according to availability for a given species and the
      precise application the transgenic animal is intended for. Here we review the
      progress in meganuclease and Sleeping Beauty transposon mediated transgenesis
      over recent years with a focus on medaka and zebrafish. We present a side-by-side
      comparison of these two approaches based on their biologic properties and provide
      interesting perspectives for future experiments and applications, which are
      different for the two techniques because of their distinct modes of action.

PMID- 18047688
TI  - Manipulating the Xenopus genome with transposable elements.
AB  - The study of amphibian embryogenesis has provided important insight into the
      mechanisms of vertebrate development. The frog Xenopus laevis has been an
      important model of vertebrate cell biology and development for many decades.
      Genetic studies in this organism are not practical because of the tetraploid
      nature of the genome and the long generation time of this species. Recently, a
      closely related frog, namely Xenopus tropicalis, has been proposed as an
      alternative system; it shares all of the physical characteristics that make X.
      laevis a useful model but has the advantage of a diploid genome and short
      generation time. The rapid accumulation of genetic resources for this animal and
      the success of pilot mutagenesis screens have helped propel this model system
      forward. Transposable elements will provide invaluable tools for manipulating the
      frog genome. These integration systems are ideally suited to transgenesis and
      insertional mutagenesis strategies in the frog. The high fecundity of the frog
      combined with the ability to remobilize transposon transgenes integrated into
      frog genome will allow large-scale insertional mutagenesis screens to be
      performed in laboratories with modest husbandry capacities.

PMID- 18047691
TI  - Germline mutagenesis mediated by Sleeping Beauty transposon system in mice.
AB  - Following the descovery of its transposition activity in mammalian culture
      systems, the Sleeping Beauty (SB) transposon has since been applied to achieve
      germline mutagenesis in mice. Initially, the transposition efficiency was found
      to be low in cultured systems, but its activity in germ cells was unexpectedly
      high. This difference in transposition efficiency was found to be largely
      dependent on chromosomal status of the host genomic DNA and transposon vector
      design. The SB transposon system has been found to be suitable for comprehensive
      mutagenesis in mice. Therefore, it is an effective tool as a forward genetics
      screen for tagged insertional mutagenesis in mice.

PMID- 18047689
TI  - Predicting preferential DNA vector insertion sites: implications for functional
      genomics and gene therapy.
AB  - Viral and transposon vectors have been employed in gene therapy as well as
      functional genomics studies. However, the goals of gene therapy and functional
      genomics are entirely different; gene therapists hope to avoid altering
      endogenous gene expression (especially the activation of oncogenes), whereas
      geneticists do want to alter expression of chromosomal genes. The odds of either
      outcome depend on a vector's preference to integrate into genes or control
      regions, and these preferences vary between vectors. Here we discuss the relative
      strengths of DNA vectors over viral vectors, and review methods to overcome
      barriers to delivery inherent to DNA vectors. We also review the tendencies of
      several classes of retroviral and transposon vectors to target DNA sequences,
      genes, and genetic elements with respect to the balance between insertion
      preferences and oncogenic selection. Theoretically, knowing the variables that
      affect integration for various vectors will allow researchers to choose the
      vector with the most utility for their specific purposes. The three principle
      benefits from elucidating factors that affect preferences in integration are as
      follows: in gene therapy, it allows assessment of the overall risks for
      activating an oncogene or inactivating a tumor suppressor gene that could lead to
      severe adverse effects years after treatment; in genomic studies, it allows one
      to discern random from selected integration events; and in gene therapy as well
      as functional genomics, it facilitates design of vectors that are better targeted
      to specific sequences, which would be a significant advance in the art of
      transgenesis.

PMID- 18047690
TI  - Pigs taking wing with transposons and recombinases.
AB  - Swine production has been an important part of our lives since the late
      Mesolithic or early Neolithic periods, and ranks number one in world meat
      production. Pig production also contributes to high-value-added medical markets
      in the form of pharmaceuticals, heart valves, and surgical materials. Genetic
      engineering, including the addition of exogenous genetic material or manipulation
      of the endogenous genome, holds great promise for changing pig phenotypes for
      agricultural and medical applications. Although the first transgenic pigs were
      described in 1985, poor survival of manipulated embryos; inefficiencies in the
      integration, transmission, and expression of transgenes; and expensive husbandry
      costs have impeded the widespread application of pig genetic engineering.
      Sequencing of the pig genome and advances in reproductive technologies have
      rejuvenated efforts to apply transgenesis to swine. Pigs provide a compelling new
      resource for the directed production of pharmaceutical proteins and the provision
      of cells, vascular grafts, and organs for xenotransplantation. Additionally,
      given remarkable similarities in the physiology and size of people and pigs,
      swine will increasingly provide large animal models of human disease where rodent
      models are insufficient. We review the challenges facing pig transgenesis and
      discuss the utility of transposases and recombinases for enhancing the success
      and sophistication of pig genetic engineering. 'The paradise of my fancy is one
      where pigs have wings.' (GK Chesterton).

PMID- 18047692
TI  - Transposons for cancer gene discovery: Sleeping Beauty and beyond.
AB  - The use of Sleeping Beauty transposons as somatic mutagens to discover cancer
      genes in hematopoietic tumors and sarcomas has been documented. Here, we discuss
      the future of Sleeping Beauty for cancer genetic studies and the potential use of
      additional transposable elements for somatic mutagenesis.

PMID- 18047693
TI  - Mutagenesis in rodents using the L1 retrotransposon.
AB  - LINE1 (L1) retrotransposons are genetic elements that are present in all
      mammalian genomes. L1s are active in both humans and mice, and are capable of
      copying themselves and inserting the copy into a new genomic location. These de
      novo insertions occasionally result in disease. Endogenous L1 retrotransposons
      can be modified to increase their activity and mutagenic power in a variety of
      ways. Here we outline the advantages of using modified L1 retrotransposons for
      performing random mutagenesis in rodents and discuss several potential
      applications.

PMID- 18047694
TI  - The DNA transposon Minos as a tool for transgenesis and functional genomic
      analysis in vertebrates and invertebrates.
AB  - Transposons are powerful tools for conducting genetic manipulation and functional
      studies in organisms that are of scientific, economic, or medical interest.
      Minos, a member of the Tc1/mariner family of DNA transposons, exhibits a low
      insertional bias and transposes with high frequency in vertebrates and
      invertebrates. Its use as a tool for transgenesis and genome analysis of rather
      different animal species is described.

PMID- 18047695
TI  - Transposon mediated transgenesis in a marine invertebrate chordate: Ciona
      intestinalis.
AB  - Achievement of transposon mediated germline transgenesis in a basal chordate,
      Ciona intestinalis, is discussed. A Tc1/mariner superfamily transposon, Minos,
      has excision and transposition activities in Ciona. Minos enables the creation of
      stable transgenic lines, enhancer detection, and insertional mutagenesis.

PMID- 18047696
TI  - Retroviral enhancer detection insertions in zebrafish combined with comparative
      genomics reveal genomic regulatory blocks - a fundamental feature of vertebrate
      genomes.
AB  - A large-scale enhancer detection screen was performed in the zebrafish using a
      retroviral vector carrying a basal promoter and a fluorescent protein reporter
      cassette. Analysis of insertional hotspots uncovered areas around developmental
      regulatory genes in which an insertion results in the same global expression
      pattern, irrespective of exact position. These areas coincide with vertebrate
      chromosomal segments containing identical gene order; a phenomenon known as
      conserved synteny and thought to be a vestige of evolution. Genomic comparative
      studies have found large numbers of highly conserved noncoding elements (HCNEs)
      spanning these and other loci. HCNEs are thought to act as transcriptional
      enhancers based on the finding that many of those that have been tested direct
      tissue specific expression in transient or transgenic assays. Although gene order
      in hox and other gene clusters has long been known to be conserved because of
      shared regulatory sequences or overlapping transcriptional units, the chromosomal
      areas found through insertional hotspots contain only one or a few developmental
      regulatory genes as well as phylogenetically unrelated genes. We have termed
      these regions genomic regulatory blocks (GRBs), and show that they underlie the
      phenomenon of conserved synteny through all sequenced vertebrate genomes. After
      teleost whole genome duplication, a subset of GRBs were retained in two copies,
      underwent degenerative changes compared with tetrapod loci that exist as single
      copy, and that therefore can be viewed as representing the ancestral form. We
      discuss these findings in light of evolution of vertebrate chromosomal
      architecture and the identification of human disease mutations.

PMID- 18047697
TI  - Transposable elements and the dynamic somatic genome.
AB  - Although alterations in the genomes of somatic cells cannot be passed on to
      future generations, they can have beneficial or detrimental effects on the host
      organism, depending on the context in which they occur. This review outlines the
      ways in which transposable elements have important consequences for somatic cell
      genomes.

PMID- 18047698
TI  - Transposable elements in fish functional genomics: technical challenges and
      perspectives.
AB  - The recent introduction of several transposable elements in zebrafish opens new
      frontiers for genetic manipulation in this important vertebrate model. This
      review discusses transposable elements as mutagenesis tools for fish functional
      genomics. We review various mutagenesis strategies that were previously applied
      in other genetic models, such as Drosophila, Arabidopsis, and mouse, that may be
      beneficial if applied in fish. We also discuss the forthcoming challenges of high
      throughput functional genomics in fish.

PMID- 18047699
TI  - Tol2: a versatile gene transfer vector in vertebrates.
AB  - The medaka fish Tol2 element is an autonomous transposon that encodes a fully
      functional transposase. The transposase protein can catalyze transposition of a
      transposon construct that has 200 and 150 base pairs of DNA from the left and
      right ends of the Tol2 sequence, respectively. These sequences contain essential
      terminal inverted repeats and subterminal sequences. DNA inserts of fairly large
      sizes (as large as 11 kilobases) can be cloned between these sequences without
      reducing transpositional activity. The Tol2 transposon system has been shown to
      be active in all vertebrate cells tested thus far, including zebrafish, Xenopus,
      chicken, mouse, and human. In this review I describe and discuss how the Tol2
      transposon is being applied to transgenic studies in these vertebrates, and
      possible future applications.

PMID- 18047700
TI  - Transposons as tools for enhancer trap screens in vertebrates.
AB  - DNA transposons are efficient tools in transgenesis and have therefore become
      popular in the analysis of the regulatory genome in vertebrates via enhancer trap
      screens. Here, I discuss recent progress in this field of research, with a focus
      on the application of one of these transposons, namely the medaka fish derived
      Tol2, to enhancer trapping in zebrafish, and how this approach compares with
      others that have a similar objective.

PMID- 18047701
TI  - Insertional mutagenesis strategies in zebrafish.
AB  - We review here some recent developments in the field of insertional mutagenesis
      in zebrafish. We highlight the advantages and limitations of the rich body of
      retroviral methodologies, and we focus on the mechanisms and concepts of new
      transposon-based mutagenesis approaches under development, including prospects
      for conditional 'gene trapping' and 'gene breaking' approaches.

PMID- 18047702
TI  - Framework for a protein ontology.
AB  - Biomedical ontologies are emerging as critical tools in genomic and proteomic
      research, where complex data in disparate resources need to be integrated. A
      number of ontologies describe properties that can be attributed to proteins. For
      example, protein functions are described by the Gene Ontology (GO) and human
      diseases by SNOMED CT or ICD10. There is, however, a gap in the current set of
      ontologies - one that describes the protein entities themselves and their
      relationships. We have designed the PRotein Ontology (PRO) to facilitate protein
      annotation and to guide new experiments. The components of PRO extend from the
      classification of proteins on the basis of evolutionary relationships to the
      representation of the multiple protein forms of a gene (products generated by
      genetic variation, alternative splicing, proteolytic cleavage, and other post
      translational modifications). PRO will allow the specification of relationships
      between PRO, GO and other ontologies in the OBO Foundry. Here we describe the
      initial development of PRO, illustrated using human and mouse proteins involved
      in the transforming growth factor-beta and bone morphogenetic protein signaling
      pathways.

PMID- 18047703
TI  - BioCAD: an information fusion platform for bio-network inference and analysis.
AB  - BACKGROUND: As systems biology has begun to draw growing attention, bio-network
      inference and analysis have become more and more important. Though there have
      been many efforts for bio-network inference, they are still far from practical
      applications due to too many false inferences and lack of comprehensible
      interpretation in the biological viewpoints. In order for applying to real
      problems, they should provide effective inference, reliable validation, rational
      elucidation, and sufficient extensibility to incorporate various relevant
      information sources. RESULTS: We have been developing an information fusion
      software platform called BioCAD. It is utilizing both of local and global
      optimization for bio-network inference, text mining techniques for network
      validation and annotation, and Web services-based workflow techniques. In
      addition, it includes an effective technique to elucidate network edges by
      integrating various information sources. This paper presents the architecture of
      BioCAD and essential modules for bio-network inference and analysis. CONCLUSION:
      BioCAD provides a convenient infrastructure for network inference and network
      analysis. It automates series of users' processes by providing data preprocessing
      tools for various formats of data. It also helps inferring more accurate and
      reliable bio-networks by providing network inference tools which utilize
      information from distinct sources. And it can be used to analyze and validate the
      inferred bio-networks using information fusion tools.

PMID- 18047704
TI  - GO for gene documents.
AB  - BACKGROUND: Annotating genes and their products with Gene Ontology codes is an
      important area of research. One approach is to use the information available
      about these genes in the biomedical literature. The goal in this paper, based on
      this approach, is to develop automatic annotation methods that can supplement the
      expensive manual annotation processes currently in place. RESULTS: Using a set of
      Support Vector Machines (SVM) classifiers we were able to achieve Fscores of
      0.49, 0.41 and 0.33 for codes of the molecular function, cellular component and
      biological process GO hierarchies respectively. We find that alternative term
      weighting strategies are not different from each other in performance and feature
      selection strategies reduce performance. The best thresholding strategy is one
      where a single threshold is picked for each hierarchy. Hierarchy level is
      important especially for molecular function and biological process. The cellular
      component hierarchy stands apart from the other two in many respects. This may be
      due to fundamental differences in link semantics. This research shows that it is
      possible to beneficially exploit the hierarchical structures by defining and
      testing a relaxed criteria for classification correctness. Finally it is possible
      to build classifiers for codes with very few associated documents but as expected
      a huge penalty is paid in performance. CONCLUSION: The GO annotation problem is
      complex. Several key observations have been made as for example about topic drift
      that may be important to consider in annotation strategies.

PMID- 18047705
TI  - A coherent graph-based semantic clustering and summarization approach for
      biomedical literature and a new summarization evaluation method.
AB  - BACKGROUND: A huge amount of biomedical textual information has been produced and
      collected in MEDLINE for decades. In order to easily utilize biomedical
      information in the free text, document clustering and text summarization together
      are used as a solution for text information overload problem. In this paper, we
      introduce a coherent graph-based semantic clustering and summarization approach
      for biomedical literature. RESULTS: Our extensive experimental results show the
      approach shows 45% cluster quality improvement and 72% clustering reliability
      improvement, in terms of misclassification index, over Bisecting K-means as a
      leading document clustering approach. In addition, our approach provides concise
      but rich text summary in key concepts and sentences. CONCLUSION: Our coherent
      biomedical literature clustering and summarization approach that takes advantage
      of ontology-enriched graphical representations significantly improves the quality
      of document clusters and understandability of documents through summaries.

PMID- 18047706
TI  - A comparison study on algorithms of detecting long forms for short forms in
      biomedical text.
AB  - MOTIVATION: With more and more research dedicated to literature mining in the
      biomedical domain, more and more systems are available for people to choose from
      when building literature mining applications. In this study, we focus on one
      specific kind of literature mining task, i.e., detecting definitions of acronyms,
      abbreviations, and symbols in biomedical text. We denote acronyms, abbreviations,
      and symbols as short forms (SFs) and their corresponding definitions as long
      forms (LFs). The study was designed to answer the following questions; i) how
      well a system performs in detecting LFs from novel text, ii) what the coverage is
      for various terminological knowledge bases in including SFs as synonyms of their
      LFs, and iii) how to combine results from various SF knowledge bases. METHOD: We
      evaluated the following three publicly available detection systems in detecting
      LFs for SFs: i) a handcrafted pattern/rule based system by Ao and Takagi, ALICE,
      ii) a machine learning system by Chang et al., and iii) a simple alignment-based
      program by Schwartz and Hearst. In addition, we investigated the conceptual
      coverage of two terminological knowledge bases: i) the UMLS (the Unified Medical
      Language System), and ii) the BioThesaurus (a thesaurus of names for all UniProt
      protein records). We also implemented a web interface that provides a virtual
      integration of various SF knowledge bases. RESULTS: We found that detection
      systems agree with each other on most cases, and the existing terminological
      knowledge bases have a good coverage of synonymous relationship for frequently
      defined LFs. The web interface allows people to detect SF definitions from text
      and to search several SF knowledge bases. AVAILABILITY: The web site is
      http://gauss.dbb.georgetown.edu/liblab/SFThesaurus.

PMID- 18047707
TI  - Extracting unrecognized gene relationships from the biomedical literature via
      matrix factorizations.
AB  - BACKGROUND: The construction of literature-based networks of gene-gene
      interactions is one of the most important applications of text mining in
      bioinformatics. Extracting potential gene relationships from the biomedical
      literature may be helpful in building biological hypotheses that can be explored
      further experimentally. Recently, latent semantic indexing based on the singular
      value decomposition (LSI/SVD) has been applied to gene retrieval. However, the
      determination of the number of factors k used in the reduced rank matrix is still
      an open problem. RESULTS: In this paper, we introduce a way to incorporate a
      priori knowledge of gene relationships into LSI/SVD to determine the number of
      factors. We also explore the utility of the non-negative matrix factorization
      (NMF) to extract unrecognized gene relationships from the biomedical literature
      by taking advantage of known gene relationships. A gene retrieval method based on
      NMF (GR/NMF) showed comparable performance with LSI/SVD. CONCLUSION: Using known
      gene relationships of a given gene, we can determine the number of factors used
      in the reduced rank matrix and retrieve unrecognized genes related with the given
      gene by LSI/SVD or GR/NMF.

PMID- 18047708
TI  - Proceedings of the Fourth Annual Conference of the MidSouth Computational Biology
      and Bioinformatics Society.

PMID- 18047709
TI  - Nanopore current transduction analysis of protein binding to non-terminal and
      terminal DNA regions: analysis of transcription factor binding, retroviral DNA
      terminus dynamics, and retroviral integrase-DNA binding.
AB  - BACKGROUND: Synthetic transcription factors (STFs) promise to offer a powerful
      new therapeutic against Cancer, AIDS, and genetic disease. Currently, 10% of
      drugs are of this type, including salicylate and tamoxifen. STFs that can
      appropriately target (and release) their transcription factor binding sites on
      native genomic DNA provide a means to directly influence cellular mRNA
      production. An effective mechanism for screening amongst transcription factor
      (TF) candidates would itself be highly valued, and such may be possible with
      nanopore cheminformatics methods. RESULTS: It is hypothesized that binding
      targets on channel-captured molecules, that are well away from the channel
      captured region, can be monitored insofar as their binding status, or history, is
      concerned. The first set of experiments we perform to explore this "transduction"
      hypothesis involve non-terminal dsDNA binding to protein (DNA TATA box receptor
      binding to TBP), where we show new experimental results and application of a new
      cheminformatics data analysis method. In the second series of experiments to
      explore the transduction hypothesis we examine terminal (blunt-ended) dsDNA
      binding to protein. We show experimental results before and after introduction of
      HIV's DNA integrase to a solution of bifunctional "Y" shaped aptamers that have
      an HIV consensus terminus exposed for interaction. CONCLUSION: X-ray
      crystallographic studies have guided our understanding of DNA structure for
      almost a century. It is still difficult, however, to translate the sequence
      directed curvature information obtained through these tools to actual systems
      found in solution. With a nanopore detector the sequence-dependent conformation
      kinetics of DNA, especially at the DNA terminus, can be studied in a new way
      while still in solution and on a single molecule basis.

PMID- 18047710
TI  - Preliminary nanopore cheminformatics analysis of aptamer-target binding strength.
AB  - BACKGROUND: Aptamers are nucleic acids selected for their ability to bind to
      molecules of interest and may provide the basis for a whole new class of
      medicines. If the aptamer is simply a dsDNA molecule with a ssDNA overhang (a
      "sticky" end) then the segment of ssDNA that complements that overhang provides a
      known binding target with binding strength adjustable according to length of
      overhang. RESULTS: Two bifunctional aptamers are examined using a nanopore
      detector. They are chosen to provide sensitive, highly modulated, blockade
      signals with their captured ends, while their un-captured regions are designed to
      have binding moieties for complementary ssDNA targets. The bifunctional aptamers
      are duplex DNA on their channel-captured portion, and single-stranded DNA on
      their portion with binding ability. For short ssDNA, the binding is merely to the
      complementary strand of DNA, which is what is studied here - for 5-base and 6
      base overhangs. CONCLUSION: A preliminary statistical analysis using hidden
      Markov models (HMMs) indicates a clear change in the blockade pattern upon
      binding by the single captured aptamer. This is also consistent with the
      hypothesis that significant conformational changes occur during the annealing
      binding event. In further work the objective is to simply extend this ssDNA
      portion to be a well-studied approximately 80 base ssDNA aptamer, joined to the
      same bifunctional aptamer molecular platform.

PMID- 18047711
TI  - Analysis of nanopore detector measurements using Machine-Learning methods, with
      application to single-molecule kinetic analysis.
AB  - BACKGROUND: A nanopore detector has a nanometer-scale trans-membrane channel
      across which a potential difference is established, resulting in an ionic current
      through the channel in the pA-nA range. A distinctive channel current blockade
      signal is created as individually "captured" DNA molecules interact with the
      channel and modulate the channel's ionic current. The nanopore detector is
      sensitive enough that nearly identical DNA molecules can be classified with very
      high accuracy using machine learning techniques such as Hidden Markov Models
      (HMMs) and Support Vector Machines (SVMs). RESULTS: A non-standard implementation
      of an HMM, emission inversion, is used for improved classification. Additional
      features are considered for the feature vector employed by the SVM for
      classification as well: The addition of a single feature representing spike
      density is shown to notably improve classification results. Another, much larger,
      feature set expansion was studied (2500 additional features instead of 1),
      deriving from including all the HMM's transition probabilities. The expanded
      features can introduce redundant, noisy information (as well as diagnostic
      information) into the current feature set, and thus degrade classification
      performance. A hybrid Adaptive Boosting approach was used for feature selection
      to alleviate this problem. CONCLUSION: The methods shown here, for more informed
      feature extraction, improve both classification and provide biologists and
      chemists with tools for obtaining a better understanding of the kinetic
      properties of molecules of interest.

PMID- 18047712
TI  - Comparison of probabilistic Boolean network and dynamic Bayesian network
      approaches for inferring gene regulatory networks.
AB  - BACKGROUND: The regulation of gene expression is achieved through gene regulatory
      networks (GRNs) in which collections of genes interact with one another and other
      substances in a cell. In order to understand the underlying function of
      organisms, it is necessary to study the behavior of genes in a gene regulatory
      network context. Several computational approaches are available for modeling gene
      regulatory networks with different datasets. In order to optimize modeling of
      GRN, these approaches must be compared and evaluated in terms of accuracy and
      efficiency. RESULTS: In this paper, two important computational approaches for
      modeling gene regulatory networks, probabilistic Boolean network methods and
      dynamic Bayesian network methods, are compared using a biological time-series
      dataset from the Drosophila Interaction Database to construct a Drosophila gene
      network. A subset of time points and gene samples from the whole dataset is used
      to evaluate the performance of these two approaches. CONCLUSION: The comparison
      indicates that both approaches had good performance in modeling the gene
      regulatory networks. The accuracy in terms of recall and precision can be
      improved if a smaller subset of genes is selected for inferring GRNs. The
      accuracy of both approaches is dependent upon the number of selected genes and
      time points of gene samples. In all tested cases, DBN identified more gene
      interactions and gave better recall than PBN.

PMID- 18047713
TI  - Duration learning for analysis of nanopore ionic current blockades.
AB  - BACKGROUND: Ionic current blockade signal processing, for use in nanopore
      detection, offers a promising new way to analyze single molecule properties, with
      potential implications for DNA sequencing. The alpha-Hemolysin transmembrane
      channel interacts with a translocating molecule in a nontrivial way, frequently
      evidenced by a complex ionic flow blockade pattern. Typically, recorded current
      blockade signals have several levels of blockade, with various durations, all
      obeying a fixed statistical profile for a given molecule. Hidden Markov Model
      (HMM) based duration learning experiments on artificial two-level Gaussian
      blockade signals helped us to identify proper modeling framework. We then apply
      our framework to the real multi-level DNA hairpin blockade signal. RESULTS: The
      identified upper level blockade state is observed with durations that are
      geometrically distributed (consistent with an a physical decay process for
      remaining in any given state). We show that mixture of convolution chains of
      geometrically distributed states is better for presenting multimodal long-tailed
      duration phenomena. Based on learned HMM profiles we are able to classify 9 base
      pair DNA hairpins with accuracy up to 99.5% on signals from same-day experiments.
      CONCLUSION: We have demonstrated several implementations for de novo estimation
      of duration distribution probability density function with HMM framework and
      applied our model topology to the real data. The proposed design could be handy
      in molecular analysis based on nanopore current blockade signal.

PMID- 18047714
TI  - Analysis of circadian pattern reveals tissue-specific alternative transcription
      in leptin signaling pathway.
AB  - BACKGROUND: It has been previously reported that most mammalian genes display a
      circadian oscillation in their baseline expression. Consequently, the phase and
      amplitude of each component of a signal transduction cascade has downstream
      consequences. RESULTS: Here, we report our analysis of alternative transcripts in
      the leptin signaling pathway which is responsible for the systemic regulation of
      macronutrient storage and energy balance. We focused on the circadian expression
      pattern of a critical component of the leptin signaling system, suppressor of
      cytokine signaling 3 (SOCS3). On an Affymetrix GeneChip 430A2 microarray, this
      gene is represented by three probe sets targeting different regions within the 3'
      end of the last exon. We demonstrate that in murine brown adipose tissue two
      downstream 3' probe sets experience circadian baseline oscillation in counter
      phase to the upstream probe set. Such differences in expression patterns are a
      telltale sign of alternative splicing within the last exon of SOCS3. In contrast,
      all three probe sets oscillated in a common phase in murine liver and white
      adipose tissue. This suggests that the regulation of SOCS3 expression in brown
      fat is tissue specific. Another component of the signaling pathway, Janus kinase
      (JAK), is directly regulated by SOCS and has alternative transcript probe sets
      oscillating in counter-phase in a white adipose tissue specific manner.
      CONCLUSION: We hypothesize that differential oscillation of alternative
      transcripts may provide a mechanism to maintain steady levels of expression in
      spite of circadian baseline variation.

PMID- 18047715
TI  - Computational analysis of biological functions and pathways collectively targeted
      by co-expressed microRNAs in cancer.
AB  - BACKGROUND: Multiple recent studies have found aberrant expression profiles of
      microRNAome in human cancers. While several target genes have been experimentally
      identified for some microRNAs in various tumors, the global pattern of cellular
      functions and pathways affected by co-expressed microRNAs in cancer remains
      elusive. The goal of this study was to develop a computational approach to global
      analysis of the major biological processes and signaling pathways that are most
      likely to be affected collectively by co-expressed microRNAs in cancer cells.
      RESULTS: We report results of computational analysis of five datasets of
      aberrantly expressed microRNAs in five human cancers published by the authors
      (pancreatic cancer) and others (breast cancer, colon cancer, lung cancer and
      lymphoma). Using the combinatorial target prediction algorithm miRgate and a two
      step data reduction procedure we have determined Gene Ontology categories as well
      as biological functions, disease categories, toxicological categories and
      signaling pathways that are: targeted by multiple microRNAs; statistically
      significantly enriched with target genes; and known to be affected in specific
      cancers. CONCLUSION: Our global analysis of predicted miRNA targets suggests that
      co-expressed miRNAs collectively provide systemic compensatory response to the
      abnormal phenotypic changes in cancer cells by targeting a broad range of
      functional categories and signaling pathways known to be affected in a particular
      cancer. Such systems biology based approach provides new avenues for biological
      interpretation of miRNA profiling data and generation of experimentally testable
      hypotheses regarding collective regulatory functions of miRNA in cancer.

PMID- 18047716
TI  - Automatic delineation of malignancy in histopathological head and neck slides.
AB  - BACKGROUND: Histopathology, which is one of the most important routines of all
      laboratory procedures used in pathology, is decisive for the diagnosis of cancer.
      Experienced histopathologists review the histological slides acquired from biopsy
      specimen in order to outline malignant areas. Recently, improvements in imaging
      technologies in terms of histological image analysis led to the discovery of
      virtual histological slides. In this technique, a computerized microscope scans a
      glass slide and generates virtual slides at a resolution of 0.25 mum/pixel. As
      the recognition of intrinsic cancer areas is time consuming and error prone, in
      this study we develop a novel method to tackle automatic squamous cell carcinoma
      of the head and neck detection problem in high-resolution, wholly-scanned
      histopathological slides. RESULTS: A density-based clustering algorithm improved
      for this study plays a key role in the determination of the corrupted cell
      nuclei. Using the Support Vector Machines (SVMs) Classifier, experimental results
      on seven head and neck slides show that the proposed algorithm performs well,
      obtaining an average of 96% classification accuracy. CONCLUSION: Recent advances
      in imaging technology enable us to investigate cancer tissue at cellular level.
      In this study we focus on wholly-scanned histopathological slides of head and
      neck tissues. In the context of computer-aided diagnosis, delineation of
      malignant regions is achieved using a powerful classification algorithm, which
      heavily depends on the features extracted by aid of a newly proposed cell nuclei
      clustering technique. The preliminary experimental results demonstrate a high
      accuracy of the proposed method.

PMID- 18047717
TI  - SVM clustering.
AB  - BACKGROUND: Support Vector Machines (SVMs) provide a powerful method for
      classification (supervised learning). Use of SVMs for clustering (unsupervised
      learning) is now being considered in a number of different ways. RESULTS: An SVM
      based clustering algorithm is introduced that clusters data with no a priori
      knowledge of input classes. The algorithm initializes by first running a binary
      SVM classifier against a data set with each vector in the set randomly labelled,
      this is repeated until an initial convergence occurs. Once this initialization
      step is complete, the SVM confidence parameters for classification on each of the
      training instances can be accessed. The lowest confidence data (e.g., the worst
      of the mislabelled data) then has its' labels switched to the other class label.
      The SVM is then re-run on the data set (with partly re-labelled data) and is
      guaranteed to converge in this situation since it converged previously, and now
      it has fewer data points to carry with mislabelling penalties. This approach
      appears to limit exposure to the local minima traps that can occur with other
      approaches. Thus, the algorithm then improves on its weakly convergent result by
      SVM re-training after each re-labeling on the worst of the misclassified vectors 
      i.e., those feature vectors with confidence factor values beyond some threshold.
      The repetition of the above process improves the accuracy, here a measure of
      separability, until there are no misclassifications. Variations on this type of
      clustering approach are shown. CONCLUSION: Non-parametric SVM-based clustering
      methods may allow for much improved performance over parametric approaches,
      particularly if they can be designed to inherit the strengths of their supervised
      SVM counterparts.

PMID- 18047718
TI  - A novel, fast, HMM-with-Duration implementation - for application with a new,
      pattern recognition informed, nanopore detector.
AB  - BACKGROUND: Hidden Markov Models (HMMs) provide an excellent means for structure
      identification and feature extraction on stochastic sequential data. An HMM-with
      Duration (HMMwD) is an HMM that can also exactly model the hidden-label length
      (recurrence) distributions - while the regular HMM will impose a best-fit
      geometric distribution in its modeling/representation. RESULTS: A Novel, Fast,
      HMM-with-Duration (HMMwD) Implementation is presented, and experimental results
      are shown that demonstrate its performance on two-state synthetic data designed
      to model Nanopore Detector Data. The HMMwD experimental results are compared to
      (i) the ideal model and to (ii) the conventional HMM. Its accuracy is clearly an
      improvement over the standard HMM, and matches that of the ideal solution in many
      cases where the standard HMM does not. Computationally, the new HMMwD has all the
      speed advantages of the conventional (simpler) HMM implementation. In preliminary
      work shown here, HMM feature extraction is then used to establish the first
      pattern recognition-informed (PRI) sampling control of a Nanopore Detector Device
      (on a "live" data-stream). CONCLUSION: The improved accuracy of the new HMMwD
      implementation, at the same order of computational cost as the standard HMM, is
      an important augmentation for applications in gene structure identification and
      channel current analysis, especially PRI sampling control, for example, where
      speed is essential. The PRI experiment was designed to inherit the high accuracy
      of the well characterized and distinctive blockades of the DNA hairpin molecules
      used as controls (or blockade "test-probes"). For this test set, the accuracy
      inherited is 99.9%.

PMID- 18047719
TI  - Systems biology approach for mapping the response of human urothelial cells to
      infection by Enterococcus faecalis.
AB  - BACKGROUND: To better understand the response of urinary epithelial (urothelial)
      cells to Enterococcus faecalis, a uropathogen that exhibits resistance to
      multiple antibiotics, a genome-wide scan of gene expression was obtained as a
      time series from urothelial cells growing as a layered 3-dimensional culture
      similar to normal urothelium. We herein describe a novel means of analysis that
      is based on deconvolution of gene variability into technical and biological
      components. RESULTS: Analysis of the expression of 21,521 genes from 30 minutes
      to 10 hours post infection, showed 9553 genes were expressed 3 standard
      deviations (SD) above the system zero-point noise in at least 1 time point. The
      asymmetric distribution of relative variances of the expressed genes was
      deconvoluted into technical variation (with a 6.5% relative SD) and biological
      variation components (>3 SD above the mode technical variability). These 1409
      hypervariable (HV) genes encapsulated the effect of infection on gene expression.
      Pathway analysis of the HV genes revealed an orchestrated response to infection
      in which early events included initiation of immune response, cytoskeletal
      rearrangement and cell signaling followed at the end by apoptosis and shutting
      down cell metabolism. The number of poorly annotated genes in the earliest time
      points suggests heretofore unknown processes likely also are involved.
      CONCLUSION: Enterococcus infection produced an orchestrated response by the host
      cells involving several pathways and transcription factors that potentially drive
      these pathways. The early time points potentially identify novel targets for
      enhancing the host response. These approaches combine rigorous statistical
      principles with a biological context and are readily applied by biologists.

PMID- 18047720
TI  - Nanopore-based kinetics analysis of individual antibody-channel and antibody
      antigen interactions.
AB  - BACKGROUND: The UNO/RIC Nanopore Detector provides a new way to study the binding
      and conformational changes of individual antibodies. Many critical questions
      regarding antibody function are still unresolved, questions that can be
      approached in a new way with the nanopore detector. RESULTS: We present evidence
      that different forms of channel blockade can be associated with the same
      antibody, we associate these different blockades with different orientations of
      "capture" of an antibody in the detector's nanometer-scale channel. We directly
      detect the presence of antibodies via reductions in channel current. Changes to
      blockade patterns upon addition of antigen suggest indirect detection of
      antibody/antigen binding. Similarly, DNA-hairpin anchored antibodies have been
      studied, where the DNA linkage is to the carboxy-terminus at the base of the
      antibody's Fc region, with significantly fewer types of (lengthy) capture
      blockades than was observed for free (un-bound) IgG antibody. The introduction of
      chaotropic agents and its effects on protein-protein interactions have also been
      observed. CONCLUSION: Nanopore-based approaches may eventually provide a direct
      analysis of the complex conformational "negotiations" that occur upon binding
      between proteins.

PMID- 18047721
TI  - A survey of DNA motif finding algorithms.
AB  - BACKGROUND: Unraveling the mechanisms that regulate gene expression is a major
      challenge in biology. An important task in this challenge is to identify
      regulatory elements, especially the binding sites in deoxyribonucleic acid (DNA)
      for transcription factors. These binding sites are short DNA segments that are
      called motifs. Recent advances in genome sequence availability and in high
      throughput gene expression analysis technologies have allowed for the development
      of computational methods for motif finding. As a result, a large number of motif
      finding algorithms have been implemented and applied to various motif models over
      the past decade. This survey reviews the latest developments in DNA motif finding
      algorithms. RESULTS: Earlier algorithms use promoter sequences of coregulated
      genes from single genome and search for statistically overrepresented motifs.
      Recent algorithms are designed to use phylogenetic footprinting or orthologous
      sequences and also an integrated approach where promoter sequences of coregulated
      genes and phylogenetic footprinting are used. All the algorithms studied have
      been reported to correctly detect the motifs that have been previously detected
      by laboratory experimental approaches, and some algorithms were able to find
      novel motifs. However, most of these motif finding algorithms have been shown to
      work successfully in yeast and other lower organisms, but perform significantly
      worse in higher organisms. CONCLUSION: Despite considerable efforts to date, DNA
      motif finding remains a complex challenge for biologists and computer scientists.
      Researchers have taken many different approaches in developing motif discovery
      tools and the progress made in this area of research is very encouraging.
      Performance comparison of different motif finding tools and identification of the
      best tools have proven to be a difficult task because tools are designed based on
      algorithms and motif models that are diverse and complex and our incomplete
      understanding of the biology of regulatory mechanism does not always provide
      adequate evaluation of underlying algorithms over motif models.

PMID- 18047722
TI  - Comparison of gene expression profiles altered by comfrey and riddelliine in rat
      liver.
AB  - BACKGROUND: Comfrey (Symphytum officinale) is a perennial plant and has been
      consumed by humans as a vegetable, a tea and an herbal medicine for more than
      2000 years. It, however, is hepatotoxic and carcinogenic in experimental animals
      and hepatotoxic in humans. Pyrrolizidine alkaloids (PAs) exist in many plants and
      many of them cause liver toxicity and/or cancer in humans and experimental
      animals. In our previous study, we found that the mutagenicity of comfrey was
      associated with the PAs contained in the plant. Therefore, we suggest that
      carcinogenicity of comfrey result from those PAs. To confirm our hypothesis, we
      compared the expression of genes and processes of biological functions that were
      altered by comfrey (mixture of the plant with PAs) and riddelliine (a prototype
      of carcinogenic PA) in rat liver for carcinogenesis in this study. RESULTS:
      Groups of 6 Big Blue Fisher 344 rats were treated with riddelliine at 1 mg/kg
      body weight by gavage five times a week for 12 weeks or fed a diet containing 8%
      comfrey root for 12 weeks. Animals were sacrificed one day after the last
      treatment and the livers were isolated for gene expression analysis. The gene
      expressions were investigated using Applied Biosystems Rat Whole Genome Survey
      Microarrays and the biological functions were analyzed with Ingenuity Analysis
      Pathway software. Although there were large differences between the significant
      genes and between the biological processes that were altered by comfrey and
      riddelliine, there were a number of common genes and function processes that were
      related to carcinogenesis. There was a strong correlation between the two
      treatments for fold-change alterations in expression of drug metabolizing and
      cancer-related genes. CONCLUSION: Our results suggest that the carcinogenesis
      related gene expression patterns resulting from the treatments of comfrey and
      riddelliine are very similar, and PAs contained in comfrey are the main active
      components responsible for carcinogenicity of the plant.

PMID- 18047723
TI  - Prediction of peptides observable by mass spectrometry applied at the
      experimental set level.
AB  - BACKGROUND: When proteins are subjected to proteolytic digestion and analyzed by
      mass spectrometry using a method such as 2D LC MS/MS, only a portion of the
      proteotypic peptides associated with each protein will be observed. The ability
      to predict which peptides can and cannot potentially be observed for a particular
      experimental dataset has several important applications in proteomics research
      including calculation of peptide coverage in terms of potentially detectable
      peptides, systems biology analysis of data sets, and protein quantification.
      RESULTS: We have developed a methodology for constructing artificial neural
      networks that can be used to predict which peptides are potentially observable
      for a given set of experimental, instrumental, and analytical conditions for 2D
      LC MS/MS (a.k.a Multidimensional Protein Identification Technology [MudPIT])
      datasets. Neural network classifiers constructed using this procedure for two
      MudPIT datasets exhibit 10-fold cross validation accuracy of about 80%. We show
      that a classifier constructed for one dataset has poor predictive performance
      with the other dataset, thus demonstrating the need for dataset specific
      classifiers. Classification results with each dataset are used to compute
      informative percent amino acid coverage statistics for each protein in terms of
      the predicted detectable peptides in addition to the percent coverage of the
      complete sequence. We also demonstrate the utility of predicted peptide
      observability for systems analysis to help determine if proteins that were
      expected but not observed generate sufficient peptides for detection. CONCLUSION:
      Classifiers that accurately predict the likelihood of detecting proteotypic
      peptides by mass spectrometry provide proteomics researchers with powerful new
      approaches for data analysis. We demonstrate that the procedure we have developed
      for building a classifier based on an individual experimental data set results in
      classifiers with accuracy comparable to those reported in the literature based on
      large training sets collected from multiple experiments. Our approach allows the
      researcher to construct a classifier that is specific for the experimental,
      instrument, and analytical conditions of a single experiment and amenable to
      local, condition-specific, implementation. The resulting classifiers have
      application in a number of areas such as determination of peptide coverage for
      protein identification, pathway analysis, and protein quantification.

PMID- 18047724
TI  - ProtQuant: a tool for the label-free quantification of MudPIT proteomics data.
AB  - BACKGROUND: Effective and economical methods for quantitative analysis of high
      throughput mass spectrometry data are essential to meet the goals of directly
      identifying, characterizing, and quantifying proteins from a particular cell
      state. Multidimensional Protein Identification Technology (MudPIT) is a common
      approach used in protein identification. Two types of methods are used to detect
      differential protein expression in MudPIT experiments: those involving stable
      isotope labelling and the so-called label-free methods. Label-free methods are
      based on the relationship between protein abundance and sampling statistics such
      as peptide count, spectral count, probabilistic peptide identification scores,
      and sum of peptide Sequest XCorr scores (SigmaXCorr). Although a number of label
      free methods for protein quantification have been described in the literature,
      there are few publicly available tools that implement these methods. We describe
      ProtQuant, a Java-based tool for label-free protein quantification that uses the
      previously published SigmaXCorr method for quantification and includes an
      improved method for handling missing data. RESULTS: ProtQuant was designed for
      ease of use and portability for the bench scientist. It implements the SigmaXCorr
      method for label free protein quantification from MudPIT datasets. ProtQuant has
      a graphical user interface, accepts multiple file formats, is not limited by the
      size of the input files, and can process any number of replicates and any number
      of treatments. In addition, ProtQuant implements a new method for dealing with
      missing values for peptide scores used for quantification. The new algorithm,
      called SigmaXCorr*, uses "below threshold" peptide scores to provide meaningful
      non-zero values for missing data points. We demonstrate that SigmaXCorr* produces
      an average reduction in false positive identifications of differential expression
      of 25% compared to SigmaXCorr. CONCLUSION: ProtQuant is a tool for protein
      quantification built for multi-platform use with an intuitive user interface.
      ProtQuant efficiently and uniquely performs label-free quantification of protein
      datasets produced with Sequest and provides the user with facilities for data
      management and analysis. Importantly, ProtQuant is available as a self-installing
      executable for the Windows environment used by many bench scientists.

PMID- 18047725
TI  - Towards validating the hypothesis of phylogenetic profiling.
AB  - BACKGROUND: As the number of fully sequenced genome increases, the need is
      greater for bioinformatics to predict or annotate genes of a newly sequenced
      genome. Ever since Eisenberg and his colleagues introduced phylogenetic profiling
      for assigning or predicting protein functions using comparative genomic analysis,
      the approach has been used in predicting function of some prokaryotic genomes
      quite successfully. Very little work has been reported in functional prediction
      of eukaryotes such as mouse and Homo sapiens species from phylogenetic profiles.
      RESULTS: We have proposed a general methodology for validating the hypothesis
      underlying phylogenetic profiling techniques, and have demonstrated it using
      eukaryotic target genomes such as Homo sapiens and mouse. The gene ontology is
      used as the gold standard for validating functional similarity among the genes in
      each cluster. We compute the functional cohesiveness of each cluster and the
      results appeared to be not encouraging towards finding functionally cohesive
      phylogenetic profiles. This result complements one recent work on the poor
      performance on functional linkage in some eukaryotic genome using phylogenetic
      profiling techniques. If we introduce a broad interpretation for functionally
      related genes as functional sub-clustering within a phylogenetic profile, then we
      have a very strong support for the hypothesis as we have shown in the paper.

PMID- 18047726
TI  - Metabonomics evaluations of age-related changes in the urinary compositions of
      male Sprague Dawley rats and effects of data normalization methods on statistical
      and quantitative analysis.
AB  - BACKGROUND: Urine from male Sprague-Dawley rats 25, 40, and 80 days old was
      analyzed by NMR and UPLC/MS. The effects of data normalization procedures on
      principal component analysis (PCA) and quantitative analysis of NMR-based
      metabonomics data were investigated. Additionally, the effects of age on the
      metabolic profiles were examined by both NMR and UPLC/MS analyses. RESULTS: The
      data normalization factor was shown to have a great impact on the statistical and
      quantitative results indicating the need to carefully consider how to best
      normalize the data within a particular study and when comparing different
      studies. PCA applied to the data obtained from both NMR and UPLC/MS platforms
      reveals similar age-related differences. NMR indicated many metabolites
      associated with the Krebs cycle decrease while citrate and 2-oxoglutarate, also
      associated with the Krebs cycle, increase in older rats. CONCLUSION: This study
      compared four different normalization methods for the NMR-based metabonomics
      spectra from an age-related study. It was shown that each method of normalization
      has a great effect on both the statistical and quantitative analyses. Each
      normalization method resulted in altered relative positions of significant PCA
      loadings for each sample spectra but it did not alter which chemical shifts had
      the highest loadings. The greater the normalization factor was related to age,
      the greater the separation between age groups was observed in subsequent PCA
      analyses. The normalization factor that showed the least age dependence was total
      NMR intensity, which was consistent with UPLC/MS data. Normalization by total
      intensity attempts to make corrections due to dietary and water intake of the
      individual animal, which is especially useful in metabonomics evaluations of
      urine. Additionally, metabonomics evaluations of age-related effects showed
      decreased concentrations of many Krebs cycle intermediates along with increased
      levels of oxidized antioxidants in urine of older rats, which is consistent with
      current theories on aging and its association with diminishing mitochondrial
      function and increasing levels of reactive oxygen species. Analysis of urine by
      both NMR and UPLC/MS provides a comprehensive and complementary means of
      examining metabolic events in aging rats.

PMID- 18047727
TI  - Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid
      riddelliine in liver of Big Blue rats.
AB  - BACKGROUND: Pyrrolizidine alkaloids (PAs) are probably the most common plant
      constituents that poison livestock, wildlife, and humans worldwide. Riddelliine
      is isolated from plants grown in the western United States and is a prototype of
      genotoxic PAs. Riddelliine was used to investigate the genotoxic effects of PAs
      via analysis of gene expression in the target tissue of rats in this study.
      Previously we observed that the mutant frequency in the liver of rats gavaged
      with riddelliine was 3-fold higher than that in the control group. Molecular
      analysis of the mutants indicated that there was a statistically significant
      difference between the mutational spectra from riddelliine-treated and control
      rats. RESULTS: Riddelliine-induced gene expression profiles in livers of Big Blue
      transgenic rats were determined. The female rats were gavaged with riddelliine at
      a dose of 1 mg/kg body weight 5 days a week for 12 weeks. Rat whole genome
      microarray was used to perform genome-wide gene expression studies. When a cutoff
      value of a two-fold change and a P-value less than 0.01 were used as gene
      selection criteria, 919 genes were identified as differentially expressed in
      riddelliine-treated rats compared to the control animals. By analysis with the
      Ingenuity Pathway Analysis Network, we found that these significantly changed
      genes were mainly involved in cancer, cell death, tissue development, cellular
      movement, tissue morphology, cell-to-cell signaling and interaction, and cellular
      growth and proliferation. We further analyzed the genes involved in metabolism,
      injury of endothelial cells, liver abnormalities, and cancer development in
      detail. CONCLUSION: The alterations in gene expression were directly related to
      the pathological outcomes reported previously. These results provided further
      insight into the mechanisms involved in toxicity and carcinogenesis after
      exposure to riddelliine, and permitted us to investigate the interaction of gene
      products inside the signaling networks.

PMID- 18047728
TI  - Structure and function predictions of the Msa protein in Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus is a human pathogen that causes a wide variety
      of life-threatening infections using a large number of virulence factors. One of
      the major global regulators used by S. aureus is the staphylococcal accessory
      regulator (sarA). We have identified and characterized a new gene (modulator of
      sarA: msa) that modulates the expression of sarA. Genetic and functional analysis
      shows that msa has a global effect on gene expression in S. aureus. However, the
      mechanism of Msa function is still unknown. Function predictions of Msa are
      complicated by the fact that it does not have a homologous partner in any other
      organism. This work aims at predicting the structure and function of the Msa
      protein. RESULTS: Preliminary sequence analysis showed that Msa is a putative
      membrane protein. It would therefore be very difficult to purify and crystallize
      Msa in order to acquire structure information about this protein. We have used
      several computational tools to predict the physico-chemical properties, secondary
      structural features, topology, 3D tertiary structure, binding sites,
      motifs/patterns/domains and cellular location. We have built a consensus that is
      derived from analysis using different algorithms to predict several structural
      features. We confirm that Msa is a putative membrane protein with three
      transmembrane regions. We also predict that Msa has phosphorylation sites and
      binding sites suggesting functions in signal transduction. CONCLUSION: Based on
      our predictions we hypothesise that Msa is a novel signal transducer that might
      be involved in the interaction of the S. aureus with its environment.

PMID- 18047729
TI  - Statistical tools for transgene copy number estimation based on real-time PCR.
AB  - BACKGROUND: As compared with traditional transgene copy number detection
      technologies such as Southern blot analysis, real-time PCR provides a fast,
      inexpensive and high-throughput alternative. However, the real-time PCR based
      transgene copy number estimation tends to be ambiguous and subjective stemming
      from the lack of proper statistical analysis and data quality control to render a
      reliable estimation of copy number with a prediction value. Despite the recent
      progresses in statistical analysis of real-time PCR, few publications have
      integrated these advancements in real-time PCR based transgene copy number
      determination. RESULTS: Three experimental designs and four data quality control
      integrated statistical models are presented. For the first method, external
      calibration curves are established for the transgene based on serially-diluted
      templates. The Ct number from a control transgenic event and putative transgenic
      event are compared to derive the transgene copy number or zygosity estimation.
      Simple linear regression and two group T-test procedures were combined to model
      the data from this design. For the second experimental design, standard curves
      were generated for both an internal reference gene and the transgene, and the
      copy number of transgene was compared with that of internal reference gene.
      Multiple regression models and ANOVA models can be employed to analyze the data
      and perform quality control for this approach. In the third experimental design,
      transgene copy number is compared with reference gene without a standard curve,
      but rather, is based directly on fluorescence data. Two different multiple
      regression models were proposed to analyze the data based on two different
      approaches of amplification efficiency integration. Our results highlight the
      importance of proper statistical treatment and quality control integration in
      real-time PCR-based transgene copy number determination. CONCLUSION: These
      statistical methods allow the real-time PCR-based transgene copy number
      estimation to be more reliable and precise with a proper statistical estimation.
      Proper confidence intervals are necessary for unambiguous prediction of trangene
      copy number. The four different statistical methods are compared for their
      advantages and disadvantages. Moreover, the statistical methods can also be
      applied for other real-time PCR-based quantification assays including
      transfection efficiency analysis and pathogen quantification.

PMID- 18047730
TI  - Cloning, analysis and functional annotation of expressed sequence tags from the
      Earthworm Eisenia fetida.
AB  - BACKGROUND: Eisenia fetida, commonly known as red wiggler or compost worm,
      belongs to the Lumbricidae family of the Annelida phylum. Little is known about
      its genome sequence although it has been extensively used as a test organism in
      terrestrial ecotoxicology. In order to understand its gene expression response to
      environmental contaminants, we cloned 4032 cDNAs or expressed sequence tags
      (ESTs) from two E. fetida libraries enriched with genes responsive to ten
      ordnance related compounds using suppressive subtractive hybridization-PCR.
      RESULTS: A total of 3144 good quality ESTs (GenBank dbEST accession number
      EH669363-EH672369 and EL515444-EL515580) were obtained from the raw clone
      sequences after cleaning. Clustering analysis yielded 2231 unique sequences
      including 448 contigs (from 1361 ESTs) and 1783 singletons. Comparative genomic
      analysis showed that 743 or 33% of the unique sequences shared high similarity
      with existing genes in the GenBank nr database. Provisional function annotation
      assigned 830 Gene Ontology terms to 517 unique sequences based on their homology
      with the annotated genomes of four model organisms Drosophila melanogaster, Mus
      musculus, Saccharomyces cerevisiae, and Caenorhabditis elegans. Seven percent of
      the unique sequences were further mapped to 99 Kyoto Encyclopedia of Genes and
      Genomes pathways based on their matching Enzyme Commission numbers. All the
      information is stored and retrievable at a highly performed, web-based and user
      friendly relational database called EST model database or ESTMD version 2.
      CONCLUSION: The ESTMD containing the sequence and annotation information of 4032
      E. fetida ESTs is publicly accessible at http://mcbc.usm.edu/estmd/.

PMID- 18047731
TI  - Robust clustering in high dimensional data using statistical depths.
AB  - BACKGROUND: Mean-based clustering algorithms such as bisecting k-means generally
      lack robustness. Although componentwise median is a more robust alternative, it
      can be a poor center representative for high dimensional data. We need a new
      algorithm that is robust and works well in high dimensional data sets e.g. gene
      expression data. RESULTS: Here we propose a new robust divisive clustering
      algorithm, the bisecting k-spatialMedian, based on the statistical spatial depth.
      A new subcluster selection rule, Relative Average Depth, is also introduced. We
      demonstrate that the proposed clustering algorithm outperforms the componentwise
      median-based bisecting k-median algorithm for high dimension and low sample size
      (HDLSS) data via applications of the algorithms on two real HDLSS gene expression
      data sets. When further applied on noisy real data sets, the proposed algorithm
      compares favorably in terms of robustness with the componentwise-median-based
      bisecting k-median algorithm. CONCLUSION: Statistical data depths provide an
      alternative way to find the "center" of multivariate data sets and are useful and
      robust for clustering.

PMID- 18047732
TI  - The alpha-hemolysin nanopore transduction detector - single-molecule binding
      studies and immunological screening of antibodies and aptamers.
AB  - BACKGROUND: Nanopore detection is based on observations of the ionic current
      threading a single, highly stable, nanometer-scale channel. The dimensions are
      such that small biomolecules and biopolymers (like DNA and peptides) can
      translocate or be captured in the channel. The identities of translocating or
      captured molecules can often be discerned, one from another, based on their
      channel blockade "signatures". There is a self-limiting aspect to a translocation
      based detection mechanism: as the channel fits tighter around the translocating
      molecule the dynamic range of the ionic current signal is reduced. In this study,
      a lengthy, highly structure, high dynamic-range, molecular capture is sought as a
      key component of a transduction-based nanopore detection platform. RESULTS: A
      specialized role, or device augmentation, involving bifunctional molecules has
      been explored. The bifunctional molecule has one function to enter and blockade
      the channel in an information-rich self-modulating manner, while the other
      function is for binding (usually), located on a non-channel-captured portion of
      the molecule. Part of the bifunctional molecule is, thus, external to the channel
      and is free to bind or rigidly link to a larger molecule of interest. What
      results is an event transduction detector: molecular events are directly
      transduced into discernible changes in the stationary statistics of the
      bifunctional molecule's channel blockade. Several results are presented of
      nanopore-based event-transduction detection. CONCLUSION: It may be possible to
      directly track the bound versus unbound state of a huge variety of molecules
      using nanopore transduction detection.

PMID- 18047733
TI  - Ubiquitin domain proteins in disease.
AB  - The human genome encodes several ubiquitin-like (UBL) domain proteins (UDPs).
      Members of this protein family are involved in a variety of cellular functions
      and many are connected to the ubiquitin proteasome system, an essential pathway
      for protein degradation in eukaryotic cells. Despite their structural similarity,
      the UBL domains appear to have a range of different targets, resulting in a
      considerable diversity with respect to UDP function. Here, we give a short
      summary of the biochemical and physiological roles of the UDPs, which have been
      linked to human diseases including neurodegeneration and cancer. Publication
      history: Republished from Current BioData's Targeted Proteins database (TPdb;
      http://www.targetedproteinsdb.com).

PMID- 18047734
TI  - The Fanconi anemia pathway and ubiquitin.
AB  - Fanconi anemia (FA) is a rare genetic disorder characterized by aplastic anemia,
      cancer/leukemia susceptibility and cellular hypersensitivity to DNA crosslinking
      agents, such as cisplatin. To date, 12 FA gene products have been identified,
      which cooperate in a common DNA damage-activated signaling pathway regulating DNA
      repair (the FA pathway). Eight FA proteins form a nuclear complex harboring E3
      ubiquitin ligase activity (the FA core complex) that, in response to DNA damage,
      mediates the monoubiquitylation of the FA protein FANCD2. Monoubiquitylated
      FANCD2 colocalizes in nuclear foci with proteins involved in DNA repair,
      including BRCA1, FANCD1/BRCA2, FANCN/PALB2 and RAD51. All these factors are
      required for cellular resistance to DNA crosslinking agents. The inactivation of
      the FA pathway has also been observed in a wide variety of human cancers and is
      implicated in the sensitivity of cancer cells to DNA crosslinking agents. Drugs
      that inhibit the FA pathway may be useful chemosensitizers in the treatment of
      cancer. Publication history: Republished from Current BioData's Targeted Proteins
      database (TPdb; http://www.targetedproteinsdb.com).

PMID- 18047735
TI  - The role of the UPS in cystic fibrosis.
AB  - CF is an inherited autosomal recessive disease whose lethality arises from
      malfunction of CFTR, a single chloride (Cl-) ion channel protein. CF patients
      harbor mutations in the CFTR gene that lead to misfolding of the resulting CFTR
      protein, rendering it inactive and mislocalized. Hundreds of CF-related mutations
      have been identified, many of which abrogate CFTR folding in the endoplasmic
      reticulum (ER). More than 70% of patients harbor the DeltaF508 CFTR mutation that
      causes misfolding of the CFTR proteins. Consequently, mutant CFTR is unable to
      reach the apical plasma membrane of epithelial cells that line the lungs and gut,
      and is instead targeted for degradation by the UPS. Proteins located in both the
      cytoplasm and ER membrane are believed to identify misfolded CFTR for UPS
      mediated degradation. The aberrantly folded CFTR protein then undergoes
      polyubiquitylation, carried out by an E1-E2-E3 ubiquitin ligase system, leading
      to degradation by the 26S proteasome. This ubiquitin-dependent loss of misfolded
      CFTR protein can be inhibited by the application of 'corrector' drugs that aid
      CFTR folding, shielding it from the UPS machinery. Corrector molecules elevate
      cellular CFTR protein levels by protecting the protein from degradation and
      aiding folding, promoting its maturation and localization to the apical plasma
      membrane. Combinatory application of corrector drugs with activator molecules
      that enhance CFTR Cl- ion channel activity offers significant potential for
      treatment of CF patients. Publication history: Republished from Current BioData's
      Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).

PMID- 18047736
TI  - Role of the ubiquitin proteasome system in Alzheimer's disease.
AB  - Though Alzheimer's disease (AD) is a syndrome with well-defined clinical and
      neuropathological manifestations, an array of molecular defects underlies its
      pathology. A role for the ubiquitin proteasome system (UPS) was suspected in the
      pathogenesis of AD since the presence of ubiquitin immunoreactivity in AD-related
      neuronal inclusions, such as neurofibrillary tangles, is seen in all AD cases.
      Recent studies have indicated that components of the UPS could be linked to the
      early phase of AD, which is marked by synaptic dysfunction, as well as to the
      late stages of the disease, characterized by neurodegeneration. Insoluble protein
      aggregates in the brain of AD patients could result from malfunction or overload
      of the UPS, or from structural changes in the protein substrates, which prevent
      their recognition and degradation by the UPS. Defective proteolysis could cause
      the synaptic dysfunction observed early in AD since the UPS is known to play a
      role in the normal functioning of synapses. In this review, we discuss recent
      observations on possible links between the UPS and AD, and the potential for
      utilizing UPS components as targets for treatment of this disease. Publication
      history: Republished from Current BioData's Targeted Proteins database (TPdb;
      http://www.targetedproteinsdb.com).

PMID- 18047737
TI  - Role of the ubiquitin proteasome system in Parkinson's disease.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder.
      Although a subject of intense research, the etiology of PD remains poorly
      understood. Recently, several lines of evidence have implicated an intimate link
      between aberrations in the ubiquitin proteasome system (UPS) and PD pathogenesis.
      Derangements of the UPS, which normally functions as a type of protein
      degradation machinery, lead to alterations in protein homeostasis that could
      conceivably promote the toxic accumulation of proteins detrimental to neuronal
      survival. Not surprisingly, various cellular and animal models of PD that are
      based on direct disruption of UPS function reproduce the most prominent features
      of PD. Although persuasive, new developments in the past few years have in fact
      raised serious questions about the link between the UPS and PD. Here I review
      current thoughts and controversies about their relationship and discuss whether
      strategies aimed at mitigating UPS dysfunction could represent rational ways to
      intervene in the disease. Publication history: Republished from Current BioData's
      Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).

PMID- 18047738
TI  - Patented small molecule inhibitors in the ubiquitin proteasome system.
AB  - Deregulation of the ubiquitin proteasome system (UPS) has been implicated in the
      pathogenesis of many human diseases, including cancer and neurodegenerative
      disorders. The recent approval of the proteasome inhibitor Velcade(R)
      (bortezomib) for the treatment of multiple myeloma and mantle cell lymphoma
      establishes this system as a valid target for cancer treatment. We review here
      new patented proteasome inhibitors and patented small molecule inhibitors
      targeting more specific UPS components, such as E3 ubiquitin ligases and
      deubiquitylating enzymes. Publication history: Republished from Current BioData's
      Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).

PMID- 18047739
TI  - The ubiquitin proteasome system in Huntington's disease and the spinocerebellar
      ataxias.
AB  - Huntington's disease and several of the spinocerebellar ataxias are caused by the
      abnormal expansion of a CAG repeat within the coding region of the disease gene.
      This results in the production of a mutant protein with an abnormally expanded
      polyglutamine tract. Although these disorders have a clear monogenic cause, each
      polyglutamine expansion mutation is likely to cause the dysfunction of many
      pathways and processes within the cell. It has been proposed that the ubiquitin
      proteasome system is impaired in polyglutamine expansion disorders and that this
      contributes to pathology. However, this is controversial with some groups
      demonstrating decreased proteasome activity in polyglutamine expansion disorders,
      some showing no change in activity and others demonstrating an increase in
      proteasome activity. It remains unknown whether the ubiquitin proteasome system
      is a feasible therapeutic target in these disorders. Here we review the
      conflicting results obtained from different assays performed in a variety of
      different systems. Publication history: Republished from Current BioData's
      Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).

PMID- 18047741
TI  - Role of the ubiquitin proteasome system in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) accounts for approximately 2.6% of all cancers in the
      United States. While early stage disease is curable by surgery, the median
      survival of metastatic disease is only 13 months. In the last decade, there has
      been considerable progress in understanding the genetics of RCC. The VHL tumor
      suppressor gene is inactivated in the majority of RCC cases. The VHL protein
      (pVHL) acts as an E3 ligase that targets HIF-1, the hypoxia inducible
      transcription factor, for degradation by the ubiquitin proteasome system (UPS).
      In RCC cases with mutant pVHL, HIF-1 is stabilized and aberrantly expressed in
      normoxia, leading to the activation of pro-survival genes such as vascular
      endothelial growth factor (VEGF). This review will focus on the defect in the UPS
      that underlies RCC and describe the development of novel therapies that target
      the UPS. Publication history: Republished from Current BioData's Targeted
      Proteins database (TPdb; http://www.targetedproteinsdb.com).

PMID- 18047742
TI  - Ubiquitin-mediated signalling and Paget's disease of bone.
AB  - Multiple steps in the RANK-NF-kappaB signalling pathway are regulated by
      ubiquitylation. Mutations affecting different components of this pathway,
      including the ubiquitin binding p62 signalling adapter protein, are found in
      patients with Paget's disease of bone or related syndromes. Here, we review the
      molecular defects and potential disease mechanisms in these conditions and
      conclude that the mutations may confer a common increased sensitivity of
      osteoclasts to cytokines, resulting in disordered NF-kappaB-dependent osteoclast
      function. Modulation of the osteoclast RANK-NF-kappaB signalling axis may
      represent a viable therapeutic strategy for Paget's disease and other conditions
      where excessive bone resorption or remodelling is a feature. Publication history:
      Republished from Current BioData's Targeted Proteins database (TPdb;
      http://www.targetedproteinsdb.com).

PMID- 18047740
TI  - Role of proteasomes in disease.
AB  - A functional ubiquitin proteasome system is essential for all eukaryotic cells
      and therefore any alteration to its components has potential pathological
      consequences. Though the exact underlying mechanism is unclear, an age-related
      decrease in proteasome activity weakens cellular capacity to remove oxidatively
      modified proteins and favours the development of neurodegenerative and cardiac
      diseases. Up-regulation of proteasome activity is characteristic of muscle
      wasting conditions including sepsis, cachexia and uraemia, but may not be rate
      limiting. Meanwhile, enhanced presence of immunoproteasomes in aging brain and
      muscle tissue could reflect a persistent inflammatory defence and anti-stress
      mechanism, whereas in cancer cells, their down-regulation reflects a means by
      which to escape immune surveillance. Hence, induction of apoptosis by synthetic
      proteasome inhibitors is a potential treatment strategy for cancer, whereas for
      other diseases such as neurodegeneration, the use of proteasome-activating or 
      modulating compounds could be more effective. Publication history: Republished
      from Current BioData's Targeted Proteins database (TPdb;
      http://www.targetedproteinsdb.com).

PMID- 18047744
TI  - Roles and potential therapeutic targets of the ubiquitin proteasome system in
      muscle wasting.
AB  - Muscle wasting, characterized by the loss of protein mass in myofibers, is in
      most cases largely due to the activation of intracellular protein degradation by
      the ubiquitin proteasome system (UPS). During the last decade, mechanisms
      contributing to this activation have been unraveled and key mediators of this
      process identified. Even though much remains to be understood, the available
      information already suggests screens for new compounds inhibiting these
      mechanisms and highlights the potential for pharmaceutical drugs able to treat
      muscle wasting when it becomes deleterious. This review presents an overview of
      the main pathways contributing to UPS activation in muscle and describes the
      present state of efforts made to develop new strategies aimed at blocking or
      slowing muscle wasting. Publication history: Republished from Current BioData's
      Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).

PMID- 18047743
TI  - HECT E3s and human disease.
AB  - In a simplified view, members of the HECT E3 family have a modular structure
      consisting of the C-terminal HECT domain, which is catalytically involved in the
      attachment of ubiquitin to substrate proteins, and N-terminal extensions of
      variable length and sequence that mediate the substrate specificity of the
      respective HECT E3. Although the physiologically relevant substrates of most HECT
      E3s have remained elusive, it is becoming increasingly clear that HECT E3s play
      an important role in sporadic and hereditary human diseases including cancer,
      cardiovascular (Liddle's syndrome) and neurological (Angelman syndrome)
      disorders, and/or in disease-relevant processes including bone homeostasis,
      immune response and retroviral budding. Thus, molecular approaches to target the
      activity of distinct HECT E3s, regulators thereof, and/or of HECT E3 substrates
      could prove valuable in the treatment of the respective diseases. Publication
      history: Republished from Current BioData's Targeted Proteins database (TPdb;
      http://www.targetedproteinsdb.com).

PMID- 18047745
TI  - Role of the ubiquitin system and tumor viruses in AIDS-related cancer.
AB  - Tumor viruses are linked to approximately 20% of human malignancies worldwide.
      This review focuses on examples of human oncogenic viruses that manipulate the
      ubiquitin system in a subset of viral malignancies; those associated with AIDS.
      The viruses include Kaposi's sarcoma herpesvirus, Epstein-Barr virus and human
      papilloma virus, which are causally linked to Kaposi's sarcoma, certain B-cell
      lymphomas and cervical cancer, respectively. We discuss the molecular mechanisms
      by which these viruses subvert the ubiquitin system and potential viral targets
      for anti-cancer therapy from the perspective of this system. Publication history:
      Republished from Current BioData's Targeted Proteins database (TPdb;
      http://www.targetedproteinsdb.com).

PMID- 18047747
TI  - Estimating disease prevalence using census data.
AB  - We describe a method of working on publicly available data to estimate disease
      prevalence in small geographic areas using Helicobacter pylori as a model
      infection. Using data from the Third National Health and Nutrition Examination
      Survey, risk parameters for H. pylori infection were obtained by logistic
      regression and validated by predicting 737.5 infections in an independent cohort
      with 736 observed infections. The prevalence of H. pylori infection in the San
      Francisco Bay Area was estimated with the probabilities obtained from a
      predictive logistic model, using risk parameters with individual-level 1990 U.S.
      Census data as input. Predicted H. pylori prevalence was also compared to gastric
      cancer incidence obtained from the Northern California Cancer Center and showed a
      positive correlation with gastric cancer incidence (P<0.001, R2=0.87), and no
      statistically significant association with other malignancies. By exclusively
      using publicly available data, these methods may be applied to selected
      conditions with strong demographic predictors.

PMID- 18047746
TI  - Wrenches in the works: drug discovery targeting the SCF ubiquitin ligase and
      APC/C complexes.
AB  - Recently, the ubiquitin proteasome system (UPS) has matured as a drug discovery
      arena, largely on the strength of the proven clinical activity of the proteasome
      inhibitor Velcade in multiple myeloma. Ubiquitin ligases tag cellular proteins,
      such as oncogenes and tumor suppressors, with ubiquitin. Once tagged, these
      proteins are degraded by the proteasome. The specificity of this degradation
      system for particular substrates lies with the E3 component of the ubiquitin
      ligase system (ubiquitin is transferred from an E1 enzyme to an E2 enzyme and
      finally, thanks to an E3 enzyme, directly to a specific substrate). The clinical
      effectiveness of Velcade (as it theoretically should inhibit the output of all
      ubiquitin ligases active in the cell simultaneously) suggests that modulating
      specific ubiquitin ligases could result in an even better therapeutic ratio. At
      present, the only ubiquitin ligase leads that have been reported inhibit the
      degradation of p53 by Mdm2, but these have not yet been developed into clinical
      therapeutics. In this review, we discuss the biological rationale, assays,
      genomics, proteomics and three-dimensional structures pertaining to key targets
      within the UPS (SCFSkp2 and APC/C) in order to assess their drug development
      potential. Publication history: Republished from Current BioData's Targeted
      Proteins database (TPdb; http://www.targetedproteinsdb.com).

PMID- 18047748
TI  - Evaluation of the impact on human salmonellosis of control measures targeted to
      Salmonella Enteritidis and Typhimurium in poultry breeding using time-series
      analysis and intervention models in France.
AB  - In France, salmonellosis is the main cause of foodborne bacterial infection with
      serotypes Enteritis (SE) and Typhimurium (ST) accounting for 70% of all cases.
      French authorities implemented a national control programme targeting SE and ST
      in poultry and eggs from October 1998 onwards. A 33% decrease in salmonellosis
      has been observed since implementation. We designed an evaluation of the impact
      of this control programme on SE and ST human infections in France. Using monthly
      Salmonella human isolate reports to the National Reference Centre we defined two
      intervention series (SE and ST) and one control series comprising serotypes not
      know to be associated with poultry or eggs. The series, from 1992 to 2003, were
      analysed using autoregressive moving average models (ARMA). To test the
      hypothesis of a reduction of SE and ST human cases >0 after the programme started
      and to estimate its size, we introduced an intervention model to the ARMA
      modelling. In contrast to the control series, we found an annual reduction of 555
      (95% CI 148-964) SE and of 492 (95% CI 0-1092) ST human infections, representing
      respectively a 21% and 18% decrease. For SE, the decrease occurred sharply after
      implementation while for ST, it followed a progressive decrease that started
      early in 1998. Our study, suggests a true relation between the Salmonella control
      programme and the subsequent decrease observed for the two targeted serotypes.
      For ST, however, the decrease prior to the intervention may also reflect control
      measures implemented earlier by the cattle and milk industry.

PMID- 18047749
TI  - An outbreak of epidemic keratoconjunctivitis in a regional ophthalmology clinic
      in New South Wales.
AB  - The objective of the study was to identify the extent and cause of an outbreak of
      epidemic keratoconjunctivitis (EKC). The study design was active case finding and
      a case-control study of clinic patients who developed symptoms of EKC between 31
      December 2005 and 31 March 2006. The main outcome measures were clinical
      procedures carried out and clinicians seen during clinic visit. Significantly
      more cases than controls had tonometry with instillation of anaesthetic drops (OR
      16.5, 95% CI 3.9-145.1, P<0.01), optical coherence tomography (OR 4.7, 95% CI 1.2
      21.9, P=0.01), or instillation of dilating drops by an orthoptist (OR 2.3, 95% CI
      1.1-4.7, P=0.01). Significantly more cases than controls were seen by one
      orthoptist (OR 21.8, 95% CI 8.2-60.0, P<0.01). Transmission of EKC within the
      clinic was probably due to contamination of either or both the anaesthetic drops
      and the tonometer head in the room used by an orthoptist. A comprehensive suite
      of strategies is required to prevent healthcare-associated EKC.

PMID- 18047750
TI  - Lessons from 40 years' surveillance of influenza in England and Wales.
AB  - The influenza virus continues to pose a significant threat to public health
      throughout the world. Current avian influenza outbreaks in humans have heightened
      the need for improved surveillance and planning. Despite recent advances in the
      development of vaccines and antiviral drugs, seasonal epidemics of influenza
      continue to contribute significantly to general practitioner workloads, emergency
      hospital admissions, and deaths. In this paper we review data produced by the
      Royal College of General Practitioners Weekly Returns Service, a sentinel general
      practice surveillance network that has been in operation for over 40 years in
      England and Wales. We show a gradually decreasing trend in the incidence of
      respiratory illness associated with influenza virus infection (influenza-like
      illness; ILI) over the 40 years and speculate that there are limits to how far an
      existing virus can drift and yet produce substantial new epidemics. The burden of
      disease caused by influenza presented to general practitioners varies
      considerably by age in each winter. In the pandemic winter of 1969/70 persons of
      working age were most severely affected; in the serious influenza epidemic of
      1989/90 children were particularly affected; in the millennium winter (in which
      the NHS was severely stretched) ILI was almost confined to adults, especially the
      elderly. Serious confounders from infections due to respiratory syncytial virus
      are discussed, especially in relation to assessing influenza vaccine
      effectiveness. Increasing pressure on hospitals during epidemic periods are shown
      and are attributed to changing patterns of health-care delivery.

PMID- 18047751
TI  - The prevalence, distribution and severity of detectable pathological lesions in
      badgers naturally infected with Mycobacterium bovis.
AB  - The Randomized Badger Culling Trial (RBCT) began in 1998 to determine the impact
      of badger culling in controlling bovine tuberculosis in cattle. A total of 1166
      badgers (14% of total) proactively culled during the RBCT were found to be
      tuberculous, offering a unique opportunity to study the pathology caused by
      Mycobacterium bovis in a large sample of badgers. Of these, 39% of adults
      (approximately 6% of all adults culled) had visible lesions (detectable at
      necropsy) of bovine tuberculosis; cubs had a lower prevalence of infection (9%)
      but a higher percentage of tuberculous cubs (55.5%) had visible lesions. Only
      approximately 1% of adult badgers had extensive, severe pathology. Tuberculous
      badgers with recorded bite wounds (approximately 5%) had a higher prevalence of
      visible lesions and a different distribution of lesions, suggesting transmission
      via bite wounds. However, the predominance of lesions in the respiratory tract
      indicates that most transmission occurs by the respiratory route.

PMID- 18047752
TI  - Multilevel analysis of risk factors for Salmonella shedding in Ontario finishing
      pigs.
AB  - The objectives of this study were to identify factors associated with Salmonella
      status at the farm, pen, and pig level; explore the nature of variation in the
      association between the pen-level Salmonella status and pen-level covariates, and
      pig-level Salmonella status and pig- and pen-level covariates; and to identify
      the relative importance of factors operating at geographical, farm, and pen level
      for Salmonella shedding of pigs. For these purposes, samples from 799 pigs and
      374 pens on 80 farms in Ontario in 2004 were collected and bacteriologically
      tested in a cross-sectional study. Census division was the least variable level,
      and farm the most variable level for shedding. Increased frequency of
      disinfection and washing with cold water were positively associated with
      Salmonella positivity, whereas liquid and mash feed and completely closed barns
      were sparing factors. After farm, pen was the second most variable level for
      shedding. However, no measured pen-level variables were associated with
      Salmonella status of pigs or pens. The shedding of Salmonella at the pig level
      tended to be associated with pig weight, and there was no random variation around
      this association. Results of this study suggest that a herd test based on
      bacteriological culture would probably have higher sensitivity if growing animals
      of lower weight were sampled instead of market weight animals, and this might be
      beneficial for Salmonella monitoring.

PMID- 18047753
TI  - Transdermal nicotine modulates strategy-based attentional semantic processing in
      non-smokers.
AB  - Nicotine has been shown to improve various aspects of cognitive processing such
      as attention and memory, however, its effects on lexical-semantic processing are
      relatively uncharted. Recent investigations of mnemonic processing in minimally
      deprived smokers suggest that nicotine might selectively modulate processes
      concerned with associative memory. This study investigated the effects of
      nicotine on lexical-semantic processing in non-smokers using a strategy-based
      lexical-decision priming paradigm. Transdermal nicotine patches (7 mg/24 h) were
      administered within a double-blind, placebo-controlled, cross-over design.
      Participants were trained to expect target words to come from a specified
      semantic category based on the prime word, although in some instances trained
      expectations were not met. Participants were presented with the stimuli at either
      a short or long stimulus onset asynchrony (SOA) to target automatic and
      attentional processing, respectively (n=12 and 17 for the short and long SOAs,
      respectively). Nicotine was found to selectively affect priming condition
      reaction times at the long SOA, indicating a nicotinic modulation of attentional
      mechanisms. Specifically, facilitation effects were dominant under placebo
      compared to a dominance of inhibition effects under nicotine. These results
      suggest that nicotine supports inhibitory attentional mechanisms in cognitively
      demanding semantic processing paradigms.

PMID- 18047754
TI  - Efficacy and safety of triiodothyronine supplementation in patients with major
      depressive disorder treated with specific serotonin reuptake inhibitors.
AB  - The thyroid hormone, triiodothyronine (T3), is used as a supplement to
      antidepressant treatment of major depression, to accelerate and enhance response
      and as an augmenter in patients who have not responded. While there is support
      from controlled trials and meta-analyses for the use of T3 in conjunction with
      tricyclic antidepressants, the evidence base for supplementation of specific
      serotonin reuptake inhibitors (SSRIs) with T3 is more limited. We reviewed the
      available literature on T3 supplementation of SSRIs including open-label studies
      and randomized controlled trials (RCTs). Five RCTs were identified. Three were
      enhancement studies in which T3 was administered concurrently with the
      antidepressant from the start of treatment and two were augmentation studies in
      which T3 was added to the antidepressant treatment of patients who had not
      responded. Three open augmentation studies were identified. The RCTs were too
      disparate in methodology to allow a meta-analysis to be performed. The
      enhancement studies are inconclusive in that one showed strongly positive effects
      of T3, one showed no effect and one showed a trend. The open augmentation studies
      supported an effect of T3 in SSRI non-responsive patients with some support from
      a large RCT; a smaller, underpowered RCT did not show efficacy. T3 was well
      tolerated in most of the studies and adverse effects do not seem to be an
      impediment to clinical use. Some of the studies identified clinical and thyroid
      function correlates of response that require further investigation. Further
      research is needed before it can be definitively established whether T3 is an
      effective supplement to SSRIs in patients with MDD. The appropriate timing of T3
      supplementation needs to be explored and also the dose and length of treatment.

PMID- 18047755
TI  - 5-HT1A gene variants and psychiatric disorders: a review of current literature
      and selection of SNPs for future studies.
AB  - 5-HT1A receptors are key components of the serotonin system, acting both pre- and
      post- synaptically in different brain areas. There is a growing amount of
      evidence showing the importance of 5-HT1A in different psychiatric disorders,
      from mood to anxiety disorders, moving through suicidal behaviour and psychotic
      disorders. Findings in the literature are not consistent with any definite 5-HT1A
      influence in psychiatric disorders. 5-HT1A gene variants have been reported to
      play some role in mood disorders, anxiety disorders and psychotic disorders.
      Again, the literature findings are not unequivocal. Concerning response to
      treatment, the C(-1019)G variant seems to be of primary interest in
      antidepressant response: C allele carriers generally show a better response to
      treatment, especially in Caucasian samples. Together with the C(-1019)G (rs6295)
      variant, the Ile28Val (rs1799921), Arg219Leu (rs1800044) and Gly22Ser (rs1799920)
      variants have been investigated in possible associations with psychiatric
      disorders, also with no definitive results. This lack of consistency can be also
      due to an incomplete gene investigation. To make progress on this point, a list
      of validated single nucleotide polymorphisms (SNPs) covering the whole gene is
      proposed for further investigations.

PMID- 18047756
TI  - Modulation by the dorsal, but not the ventral, hippocampus of the expression of
      behavioural sensitization to amphetamine.
AB  - Although the dorsal hippocampus (DH) and the ventral hippocampus (VH) densely
      innervate the nucleus accumbens, which mediates the expression of behavioural
      sensitization, the respective and specific contribution of DH and VH in the
      expression of behavioural sensitization to amphetamine has not been investigated.
      In the present study, we investigated how lidocaine infused in DH or VH modulated
      behavioural locomotor sensitization induced by repeated administration of
      systemic amphetamine. Rats, well habituated to their environmental conditions and
      experimental protocol, were given repeated administration of systemic
      amphetamine. Once behavioural sensitization was developed, rats were challenged
      with amphetamine and infused with saline (controls) or lidocaine into DH or VH.
      We found that reversible inhibition by lidocaine of DH, but not VH, blocks the
      expression of behavioural sensitization to amphetamine. Control animals injected
      with saline solution do express behavioural sensitization. Our results bring new
      insights on the role of the hippocampus complex in the expression of behavioural
      sensitization, indicating that, in individuals well habituated to the drug
      associated context, DH but not VH would play a key role. The results provide
      experimental evidence for clinical studies in human addicts that have
      demonstrated that exposure to environmental stimuli associated with drug-taking
      behaviour elicits craving and can promote relapse, and further suggest that in
      drug abusers, once addiction has occurred, the contextual and spatial conditions
      that are associated with drug consumption may play a critical role in the
      maintenance of drug abuse.

PMID- 18047757
TI  - Reduced prepulse inhibition is associated with increased hypnotizability.
AB  - Hypnosis involves the manipulation of conscious attentional discrimination. The
      prepulse inhibition (PPI) paradigm assesses primary unconscious information
      processing. We investigated the correlation between hypnotizability and PPI of
      the startle reflex. Forty-eight healthy subjects were evaluated with the Stanford
      Hypnotic Susceptibility Scale, Form C (SHSS:C) and acoustic PPI. Subjects were
      divided into low, medium, and high hypnotizable groups. The low-hypnotizable
      group showed a significantly higher inhibition of the startle response, at lead
      intervals 60 ms and 120 ms, than did the medium- and high-hypnotizable groups. We
      conclude that hypnotizability and PPI may be negatively correlated. These
      findings lend further support for the role of dopaminergic neurotransmission
      mechanisms in the determination of hypnotizability levels.

PMID- 18047758
TI  - Re-operation for secondary hyperparathyroidism.
AB  - OBJECTIVE: In cases of re-operation for secondary hyperparathyroidism, to
      evaluate the extent to which the location of recurrent hyperplasia was predicted
      by (1) operative data from the first intervention, and (2) pre-operative imaging
      (before the re-operation). METHODS: The files of 18 patients undergoing surgery
      for recurrent secondary hyperparathyroidism were reviewed. The surgical findings
      were compared both with the report of the initial operation and with the results
      of pre-operative imaging (i.e. ultrasonography, Mibi scintigraphy or computed
      tomography). RESULTS: The location of the recurrent hyperplasia corresponded with
      the data for the primary intervention in about one-third of patients. There was a
      partial correlation in one-third of patients, and no correlation at all in one
      third. Pre-operative imaging enabled better prediction of the location of
      recurrent disease. CONCLUSION: Surgeons should have both sources of information
      at their disposal when planning a re-intervention for secondary
      hyperparathyroidism. However, in our series, the predictive value of imaging was
      superior to that of information deduced from the previous surgical record.

PMID- 18047759
TI  - Case report of glomus jugulare tumour associated with a posterior fossa cyst.
AB  - A subgroup of complex glomus jugulare tumours exists. This includes: multiple,
      giant or neuropeptide-secreting lesions; those associated with other lesions,
      such as dural arterio-venous malformation or an adrenal tumour; and tumours in
      which there has been previous treatment with adverse outcome. To our knowledge,
      we present the first case of a glomus jugulare tumour associated with a posterior
      fossa cyst. This entity should be included in the subgroup of complex glomus
      jugulare tumours.

PMID- 18047760
TI  - Follow up after middle-ear ventilation tube insertion: what is needed and when?
AB  - INTRODUCTION: There is a paucity of evidence to guide the post-operative follow
      up of patients undergoing middle-ear ventilation tube insertion for the first
      time. This study was conceived to identify current practice at our institution
      (Ninewells Hospital, Dundee) and to inform subsequent change in our follow-up
      procedure. METHODS: Two cycles of data collection and analysis were performed.
      All paediatric patients undergoing ventilation tube insertion for the first time
      were identified. Patients who had previously undergone ventilation tube insertion
      or additional procedures such as adenoidectomy or tonsillectomy were excluded.
      The first data collection period comprised all of the year 2000, and the second
      18 months over 2003-2004. A minimum of 20 months' follow up was allowed for. Data
      regarding clinical findings and audiometry were recorded at each follow-up
      appointment. RESULTS: We identified a total of 50 patients meeting our criteria
      for inclusion in the first cohort. There were a total of 156 appointments between
      surgery and data collection (a mean of 3.12 per child). A total of 113 (72 per
      cent) appointments lead to no medical intervention. The only statistically
      significant difference between patients requiring further ventilation tube
      insertion (n = 10) and those not requiring further treatment during the study
      period (n = 40) was the average hearing threshold (p < 0.01). These findings
      prompted a change in the post-operative regime; all patients undergoing
      ventilation tube insertion were subsequently seen at three months for a pure tone
      audiogram, and further review depended on clinical and audiometric findings.
      Records for 84 children were identified and collected for the second cohort,
      there were a total of 154 appointments (a mean of 1.83 per child). In only 18
      appointments (12 per cent) were normal findings and hearing recorded and children
      given a further review appointment. Sixteen of 29 (55 per cent) children with
      abnormal clinical findings (otorrhoea, tube blockage or extrusion) required some
      form of intervention (p < 0.05). Twenty-six had a mean hearing threshold worse
      than 20 dB at first review. Nineteen (73 per cent) required further intervention
      of some sort (p < 0.01). CONCLUSIONS: Our study demonstrated that the vast
      majority of review appointments resulted in no clinical intervention. We
      therefore question the need for regular follow up in this patient group. Twenty
      per cent (10 of 50 and 18 of 84) of our patients required further ventilation
      tube insertion within the study periods. This is consistent with rates reported
      in the literature. Children with abnormal clinical findings or a mean hearing
      threshold greater than 20 dB were significantly more likely to require further
      intervention. We would recommend one post-operative review with audiometry, three
      months after surgery. At this initial appointment, further review should be
      offered to those children with poor hearing, early extrusion, blockage or
      infection, as they are more likely to require further ventilation tube insertion.
      This strategy is dependent on good links with community primary care providers
      and easy access to secondary care for further management, should this be
      required.

PMID- 18047762
TI  - Physical and emotional disturbances in children with adenotonsillar hypertrophy.
AB  - OBJECTIVE: Enlarged tonsils and adenoids (part of Waldeyer's ring) are
      responsible for obstructive sleep disordered breathing. Obstructive sleep
      disordered breathing episodes lead to hypoxaemia, hypercapnia and a state of
      arousal, all of which affect normal development of the nervous system. In this
      study, two hypotheses were tested: (1) obstructive sleep disordered breathing is
      caused by adenotonsillar hypertrophy and is associated with hypoxia and brain
      dysfunction; and (2) children with obstructive sleep disordered breathing more
      commonly display emotional lability, depressive behaviour and anxiety. MATERIAL
      AND METHODS: A total of 225 children were examined. The study group consisted of
      121 children with adenotonsillar hypertrophy (87 aged six to nine years and 34
      aged 10 to 13 years) and with obstructive sleep apnoeas and hypopnoeas confirmed
      by polysomnography. Patients were compared with 104 children with no obstructive
      sleep disordered breathing and no adenotonsillar hypertrophy (74 aged six to nine
      years and 30 aged 10 to 13 years). The following tests were used to measure the
      children's emotional disorders: the children's depression inventory; the state
      trait anxiety inventory for children; and the emotional instability scale. The
      average values and standard deviations were calculated for all results. Student's
      t-test was used to compare differences in all groups of children. The minimum
      level of p < 0.05 was set as statistically significant. RESULTS: Children with
      adenotonsillar hypertrophy are more likely to experience poor brain development
      and sleep problems. They also have emotional disturbances. In the sick and
      healthy children aged six to nine years, mean results for the emotional
      instability scale were statistically significantly different in the two groups,
      being higher in children with adenotonsillar hypertrophy than in healthy
      children. Mean values for the children's depression inventory test were higher in
      children with adenotonsillar hypertrophy, but the differences were not
      statistically significant. In the state-trait anxiety inventory for children
      test, the mean T score was T = 1.760 and the level of significance was p = 0.08
      for both groups. Since the standard level of significance was p < 0.05, the
      differences in mean values for the state-trait anxiety inventory for children
      test bordered on statistical significance. There were no differences between
      tests results in the older children (10 to 13 years). CONCLUSIONS: Recent studies
      have confirmed the negative emotional effect of adenotonsillar hypertrophy
      induced obstructive sleep disordered breathing in children aged six to nine
      years. The main problems are emotional lability, and anxiety and depressive
      disturbances. Such emotional problems subside in older children (aged 10 to 13
      years).

PMID- 18047761
TI  - Induction chemotherapy with S-1 plus cisplatin in patients with locally advanced
      squamous cell carcinoma of the head and neck.
AB  - OBJECTIVE: This study was performed to assess the efficacy and safety profile of
      combination treatment with S-1 and cisplatin in patients with locally advanced
      squamous cell carcinoma of the head and neck. DESIGN: Eligibility criteria
      comprised: histologically confirmed squamous cell carcinoma of the head and neck;
      stage three or four disease with no evidence of distant metastasis; evaluable
      lesions; adequate organ function; age 20-80 years; and a performance status of
      two or less. Cisplatin was infused over one hour on day one (75 mg/m2) and S-1
      was administered orally for 14 consecutive days (days two to 15). The dosages of
      S-1 were calculated according to the patients' body surface area: 50 mg twice a
      day (body surface area 1.5 m2). Each course was repeated every three weeks. After
      two courses, tumour response was evaluated by computed tomography and
      laryngoscopy. If a response was evident (either complete or partial), the patient
      received one more course of chemotherapy, before undergoing radical treatment
      such as radiotherapy or surgery. RESULTS: All 30 patients were assessable for
      toxicity, and 29 patients for treatment response. The overall response was 89.7
      per cent (complete response: nine; partial response: 17). The two-year estimated
      overall survival rate was 79.2 per cent. Adverse reactions occurred 128 times
      during 81 courses in the 30 cases. The most common grade three to four adverse
      event was neutropenia, which occurred in eight patients. Cases of non
      haematological grade three or four toxicity included nausea and vomiting in four
      patients, stomatitis in two and diarrhoea in one. CONCLUSION: S-1 plus cisplatin
      combination chemotherapy is effective against locally advanced squamous cell
      carcinoma of the head and neck, with only mild toxicity.

PMID- 18047763
TI  - Post-tonsillectomy dysgeusia with weight loss: possible involvement of soft
      palate.
AB  - OBJECTIVE: To demonstrate the importance of detailed, multidisciplinary
      examination of patients with post-tonsillectomy taste distortions, and to show
      that post-tonsillectomy dysgeusia may originate in the caudal part of the soft
      palate. CASE REPORT: We describe a 29-year-old man who suffered from severe post
      tonsillectomy dysgeusia and phantogeusia with secondary weight loss and
      depression-like symptomatology. The patient had normal electrogustometric
      thresholds and sensitivity to touch on the posterior tongue. In contrast,
      elevated taste threshold and reduced sensitivity to touch was found on the caudal
      part of the soft palate (the palatoglossal arches). More marked elevation of
      electrogustometric threshold and insensitivity to touch on the right
      palatoglossal arch correlated with post-operative haemorrhage from the right
      tonsillar fossa. Psychiatric examination excluded major depression, eating
      disorders and drug abuse. CONCLUSIONS: Dysgeusia constitutes a rare but
      significant complication of tonsillectomy. Damage to the lingual branch of the
      glossopharyngeal nerve innervating the posterior tongue is thought to be a major
      cause of this complication. However, damage to the tonsillar branches of the
      glossopharyngeal nerve and the soft palate should also be considered as a cause
      of post-tonsillectomy dysgeusia. Further studies are needed to assess whether
      post-operative haemorrhage could indicate heightened risk of dysgeusia.

PMID- 18047764
TI  - Anticonvulsants for the treatment of behavioral and psychological symptoms of
      dementia: a literature review.
AB  - OBJECTIVE: To review and summarize the currently available data on the use of
      anticonvulsant mood stabilizers (carbamazepine, valproic acid, gabapentin,
      lamotrigine, topiramate) in the treatment of behavioral and psychological
      symptoms of dementia (BPSD); to determine whether these medications can be
      recommended for routine clinical use. METHODS: Literature search in five
      databases (PubMed, MEDLINE, EMBASE, PsychINFO and COCHRANE collaboration) and
      analysis of the randomized controlled double-blinded clinical trials found
      therein. RESULTS: A total of seven RCTs were identified (two for carbamazepine
      and five for valproate). One study showed statistically significant improvement
      of BPSD in the medication group in comparison to the placebo group; five studies
      showed no significant differences; one study showed statistically significant
      worsening of the symptoms in the medication group vs. placebo. The majority of
      the studies reported significantly more frequent adverse effects in the
      medication group. CONCLUSION: Although clearly beneficial in some patients,
      anticonvulsant mood stabilizers cannot be recommended for routine use in the
      treatment of BPSD at the present time.

PMID- 18047765
TI  - The relationship between elderly suicide rates and mental health funding, service
      provision and national policy: a cross-national study.
AB  - BACKGROUND: Elderly suicide rates may be influenced by mental health funding,
      service provision and national policy. METHODS: A cross-national study examining
      the relationship between elderly suicide rates and (i) the presence of national
      policy on mental health, (ii) funding for mental health, and (iii) measures of
      mental health service provision was undertaken by utilizing data from the World
      Health Organization website. RESULTS: The main findings are: (i) there is no
      relationship between suicide rates in both sexes in both elderly age-bands and
      different measures of mental health policy, except they were increased in
      countries with a substance abuse policy; and (ii) suicide rates in both sexes in
      both elderly age-bands were higher in countries with greater provision of mental
      health services, including the number of psychiatric beds, psychiatrists,
      psychiatric nurses, and the availability of training in mental health for primary
      care professionals. CONCLUSIONS: Cross-national ecological studies using national
      level aggregate data are not helpful in establishing a causal relationship (and
      the direction of this relationship) between elderly suicide rates and mental
      health funding, service provision and national policies. The impact of
      introducing national policies on mental health, increasing funding for mental
      health services and increasing mental health service provision on elderly suicide
      rates requires further examination in longitudinal within-country studies.

PMID- 18047767
TI  - Predicting young adult social functioning from developmental trajectories of
      externalizing behaviour.
AB  - BACKGROUND: The long-term consequences of child and adolescent externalizing
      problems often involve a wide spectrum of social maladaptation in adult life. The
      purpose of this study was to describe the predictive link of child and adolescent
      externalizing developmental trajectories to social functioning in adulthood.
      METHOD: Social functioning was predicted from developmental trajectories of
      parent-reported aggression, opposition, property violations and status violations
      that were defined in a longitudinal multiple birth cohort study of 2,076 males
      and females aged 4-18 years. Social functioning was assessed using self-reports
      by young adults aged 18-30 years. Linear and logistic regression analyses were
      used to describe the extent to which developmental trajectories are prospectively
      related to social functioning. RESULTS: Children with high-level trajectories of
      opposition and status violations reported more impaired social functioning as
      young adults than children with high-level trajectories of aggression and
      property violations. Young adults who showed onset of problems in adolescence
      reported overall less impaired social functioning than individuals with high
      level externalizing problems starting in childhood. Overall, males reported more
      impaired social functioning in adulthood than females. However, females with
      persistent high-level externalizing behaviour reported more impairment in
      relationships than males with persistent high-level externalizing behaviour.
      CONCLUSION: The long-term consequences of high levels of opposition and status
      violations in childhood to serious social problems during adulthood are much
      stronger than for individuals who show only high levels of aggressive antisocial
      behaviours.

PMID- 18047766
TI  - Co-morbid major depression and generalized anxiety disorders in the National
      Comorbidity Survey follow-up.
AB  - BACKGROUND: Although generalized anxiety disorder (GAD) and major depressive
      episode (MDE) are known to be highly co-morbid, little prospective research has
      examined whether these two disorders predict the subsequent first onset or
      persistence of the other or the extent to which other predictors explain the time
      lagged associations between GAD and MDE. METHOD: Data were analyzed from the
      nationally representative two-wave panel sample of 5001 respondents who
      participated in the 1990-1992 National Comorbidity Survey (NCS) and the 2001-2003
      NCS follow-up survey. Both surveys assessed GAD and MDE. The baseline NCS also
      assessed three sets of risk factors that are considered here: childhood
      adversities, parental history of mental-substance disorders, and respondent
      personality. RESULTS: Baseline MDE significantly predicted subsequent GAD onset
      but not persistence. Baseline GAD significantly predicted subsequent MDE onset
      and persistence. The associations of each disorder with the subsequent onset of
      the other attenuated with time since onset of the temporally primary disorder,
      but remained significant for over a decade after this onset. The risk factors
      predicted onset more than persistence. Meaningful variation was found in the
      strength and consistency of associations between risk factors and the two
      disorders. Controls for risk factors did not substantially reduce the net cross
      lagged associations of the disorders with each other. CONCLUSIONS: The existence
      of differences in risk factors for GAD and MDE argues against the view that the
      two disorders are merely different manifestations of a single underlying
      internalizing syndrome or that GAD is merely a prodrome, residual, or severity
      marker of MDE.

PMID- 18047768
TI  - Detecting common mental disorders in primary care in India: a comparison of five
      screening questionnaires.
AB  - BACKGROUND: Screening of patients for common mental disorders (CMDs) is needed in
      primary-care management programmes. This study aimed to compare the screening
      properties of five widely used questionnaires. METHOD: Adult attenders in five
      primary-care settings in India were recruited through systematic sampling. Four
      questionnaires were administered, in pairs, in random order to participants: the
      General Health Questionnaire (GHQ, 12 items); the Primary Health Questionnaire
      (PHQ, nine items); the Kessler Psychological Distress Scale (K10, 10 items), and
      from which we could extract the score of the shorter 6-item K6; and the Self
      Reporting Questionnaire (SRQ, 20 items). All participants were interviewed with a
      structured lay diagnostic interview, the Revised Clinical Interview Schedule (CIS
      R). RESULTS: Complete data were available for 598 participants (participation
      rate 99.3%). All five questionnaires showed moderate to high discriminating
      ability; the GHQ and SRQ showed the best results. All five showed moderate to
      high degrees of correlation with one another, the poorest being between the two
      shortest questionnaires, K6 and PHQ. All five had relatively good internal
      consistency. However, the positive predictive value (PPV) of the questionnaires
      compared with the diagnostic interview ranged from 51% to 77% at the optimal cut
      off scores. CONCLUSIONS: There is little difference in the ability of these
      questionnaires to identify cases accurately, but none showed high PPVs without a
      considerable compromise on sensitivity. Hence, the choice of an optimum cut-off
      score that yields the best balance between sensitivity and PPV may need to be
      tailored to individual settings, with a higher cut-off being recommended in
      resource-limited primary-care settings.

PMID- 18047769
TI  - A momentary assessment study of the reputed emotional phenotype associated with
      borderline personality disorder.
AB  - BACKGROUND: Stress is postulated to play an essential role in the expression of
      core borderline symptoms. However, the phenomenology of stress reactivity in
      borderline personality disorder remains unclear. The current study investigated
      the phenomenology of stress sensitivity in borderline personality disorder in the
      flow of daily life and compared this with stress sensitivity in patients
      suffering from psychotic disorders, a group so far known to report the largest
      reactivity to stress. METHOD: A total of 44 borderline patients, 42 patients with
      psychotic disorder and 49 healthy controls were studied with the Experience
      Sampling Method (a structured diary technique assessing current context and mood
      in daily life) to assess: (1) appraised subjective stress related to daily events
      and activities; and (2) emotional reactivity conceptualized as changes in
      positive and negative affect. RESULTS: Multilevel regression analysis revealed
      that subjects with borderline personality disorder experienced significantly more
      emotional reactivity to daily life stress compared with both patients with
      psychosis and healthy controls, as evidenced by a larger increase in negative
      affect and a larger decrease in positive affect following stress. CONCLUSION:
      These results are the first to ecologically validate the incorporation of stress
      reactive symptoms in the diagnosis of borderline personality disorder. Borderline
      patients continually react stronger than patients with psychosis and healthy
      controls to small disturbances that continually happen in the natural flow of
      everyday life. Altered emotional stress reactivity may define borderline
      personality disorder.

PMID- 18047770
TI  - Mortality in offspring of mothers with psychotic disorder.
AB  - BACKGROUND: Previous studies suggest that offspring of mothers with psychotic
      disorders have an almost two-fold higher mortality risk from birth until early
      adulthood. We investigated predictors of mortality from late adolescence until
      middle age in offspring of mothers with psychotic disorders. METHOD: The Helsinki
      High-Risk Study follows up offspring (n=337) of women treated for schizophrenia
      spectrum disorders in mental hospitals in Helsinki before 1975. Factors related
      to mortality up to 2005 among offspring of these mothers was investigated with a
      survival model. Hazard rate ratios (HRR) were calculated using sex, diagnosis of
      psychotic disorder, childhood socio-economic status, maternal diagnosis, and
      maternal suicide attempts and aggressive symptoms as explanatory variables. The
      effect of family was investigated by including a frailty term in the model. We
      also compared mortality between the high-risk group and the Finnish general
      population. RESULTS: Within the high-risk group, females had lower all-cause
      mortality (HRR 0.43, p=0.05) and mortality from unnatural causes (HRR 0.24,
      p=0.03) than males. Having themselves been diagnosed with a psychotic disorder
      was associated with higher mortality from unnatural causes (HRR 4.76, p=0.01),
      while maternal suicide attempts were associated with higher suicide mortality
      (HRR 8.64, p=0.03). Mortality in the high-risk group was over two-fold higher
      (HRR 2.44, p<0.0001) than in the general population, and remained significantly
      higher when high-risk offspring who later developed psychotic disorders were
      excluded from the study sample (HRR 2.30, p<0.0001). CONCLUSIONS: Offspring of
      mothers with psychotic disorder are at increased risk of several adverse
      outcomes, including premature death.

PMID- 18047771
TI  - Experiential features used by patients with schizophrenia to differentiate
      'voices' from ordinary verbal thought.
AB  - BACKGROUND: Determining how patients distinguish auditory verbal hallucinations
      (AVHs) from their everyday thoughts may shed light on neurocognitive processes
      leading to these symptoms. METHOD: Fifty patients reporting active AVHs
      ('voices') with a diagnosis of schizophrenia or schizo-affective disorder were
      surveyed using a structured questionnaire. Data were collected to determine: (a)
      the degree to which patients distinguished voices from their own thoughts; (b)
      the degree to which their thoughts had verbal form; and (c) the experiential
      basis for identifying experiences as voices versus their own verbal thoughts. Six
      characteristics of acoustic/verbal images were considered: (1) non-self speaking
      voice, (2) loudness, (3) clarity, (4) verbal content, (5) repetition of verbal
      content, and (6) sense of control. RESULTS: Four subjects were eliminated from
      the analysis because they reported absent verbal thought or a total inability to
      differentiate their own verbal thoughts from voices. For the remaining 46
      patients, verbal content and sense of control were rated as most salient in
      distinguishing voices from everyday thoughts. With regard to sensory/perceptual
      features, identification of speaking voice as non-self was more important in
      differentiating voices from thought than either loudness or clarity of sound
      images. CONCLUSIONS: Most patients with schizophrenia and persistent AVHs clearly
      distinguish these experiences from their everyday thoughts. An adequate
      mechanistic model of AVHs should account for distinctive content, recognizable
      non-self speaking voices, and diminished sense of control relative to ordinary
      thought. Loudness and clarity of sound images appear to be of secondary
      importance in demarcating these hallucination experiences.

PMID- 18047772
TI  - The mental health of clean-up workers 18 years after the Chernobyl accident.
AB  - BACKGROUND: The psychological aftermath of the Chernobyl accident is regarded as
      the largest public health problem unleashed by the accident to date. Yet the
      mental health of the clean-up workers, who faced the greatest radiation exposure
      and threat to life, has not been systematically evaluated. This study describes
      the long-term psychological effects of Chernobyl in a sample of clean-up workers
      in Ukraine. METHOD: The cohorts were 295 male clean-up workers sent to Chernobyl
      between 1986 and 1990 interviewed 18 years after the accident (71% participation
      rate) and 397 geographically matched controls interviewed as part of the Ukraine
      World Mental Health (WMS) Survey 16 years after the accident. The World Health
      Organization (WHO) Composite International Diagnostic Interview (CIDI) was
      administered. We examined group differences in common psychiatric disorders,
      suicide ideation and severe headaches, differential effects of disorder on days
      lost from work, and in the clean-up workers, the relationship of exposure
      severity to disorder and current trauma and somatic symptoms. Analyses were
      adjusted for age in 1986 and mental health prior to the accident. RESULTS:
      Relatively more clean-up workers than controls experienced depression (18.0% v.
      13.1%) and suicide ideation (9.2% v. 4.1%) after the accident. In the year
      preceding interview, the rates of depression (14.9% v. 7.1%), post-traumatic
      stress disorder (PTSD) (4.1% v. 1.0%) and headaches (69.2% v. 12.4%) were
      elevated. Affected workers lost more work days than affected controls. Exposure
      level was associated with current somatic and PTSD symptom severity. CONCLUSIONS:
      Long-term mental health consequences of Chernobyl were observed in clean-up
      workers.

PMID- 18047774
TI  - Characterization of intracellular Ca2+ transient by the hybrid logistic function
      in aequorin-injected rabbit and mouse papillary muscles.
AB  - Myocardial intracellular calcium (Ca2+) transients (CaTs) regulate tension
      generation and relaxation. Isometric tension curves are often analyzed using
      exponential equations; however, we previously demonstrated that hybrid logistic
      (HL) functions, which describe the difference between two S-shaped logistic
      functions, provide more accurate representations. In the present study, we
      investigated the potential application of HL functions for analyzing CaTs
      directly. CaTs were measured using the calcium-sensitive bioluminescent protein,
      aequorin, in 7 isolated rabbit right ventricular and 15 isolated mouse left
      ventricular papillary muscles. CaT data were fit by the least-squares method
      using HL and polynomial exponential (PE) function equations. The mean correlation
      coefficient (r) values of HL and PE fits were 0.9934 vs. 0.9523 in rabbit and
      0.9980 vs. 0.9407 in mouse, respectively. The Z transformation of r value and the
      adjusted coefficient of determination (r squares) were higher, and the residual
      mean squares and Akaike information criterion values, which estimate goodness of
      fit between functions with different numbers of parameters, were lower for the HL
      curves than for the PE curves in both rabbit and mouse. There were significant
      correlations between the calculated values from the best-fit HL function curve
      and the primary CaT data. Thus the HL function curves more accurately described
      the amplitudes and time courses of CaTs in both rabbit and mouse papillary
      muscles. We speculate that the first logistic component curve reflects the
      concentration and time course of Ca2+ inflow into the cytoplasmic space, and that
      the second logistic component curve reflects the concentrations and time courses
      of Ca2+ removal from the cytoplasmic space as well as Ca2+ binding to troponin.
      This approach might provide a more robust model for studying CaTs and cardiac
      cycle regulation.

PMID- 18047775
TI  - Decreasing the incidence and impact of infections in neutropenic patients:
      evidence from meta-analyses of randomized controlled trials.
AB  - BACKGROUND: [corrected] Neutropenia is a common complication of intensive
      chemotherapy in patients with solid organ or hematologic malignancies that is
      associated with a high risk for life-threatening infections. Many interventions
      have been employed in order to limit the incidence of these infections or to
      treat them when the prophylactic measures fail. SCOPE: The commonest
      characteristic of the randomized controlled trials (RCTs) conducted on this issue
      was the small sample size. In addition, if RCTs studying the prophylactic
      interventions were excluded, the aim of most of the rest of relevant RCTs was to
      prove the equal effectiveness of the tested interventions in terms of treatment
      success. We searched PubMed and Cochrane database to identify meta-analyses of
      RCTs in the field of febrile neutropenia. RESULTS: The most prominent findings of
      these meta-analyses were the promising effect, although based on open label RCTs,
      of antimicrobial prophylaxis with fluoroquinolones on the mortality of all
      neutropenic patients and the beneficial effect of antifungal prophylaxis on
      mortality of neutropenic patients with allogeneic hematopoetic stem cell
      transplantation. Another noteworthy finding was the higher mortality associated
      with empiric cefepime treatment when compared with other beta-lactams. In other
      cases, the findings of the published meta-analyses either confirmed or
      consolidated the results of individual RCTs. CONCLUSION: Meta-analyses are very
      useful for obtaining a better overview and to provide some general qualitative
      and quantitative conclusions, but are not always a substitute for appropriately
      powered, well-designed RCTs. In addition, the reported findings should be
      interpreted with caution taking into account the limitations of various
      methodological aspects of meta-analysis in general, as well as the limitations of
      the individual meta-analyses in this field.

PMID- 18047776
TI  - Ibandronate and the risk of non-vertebral and clinical fractures in women with
      postmenopausal osteoporosis: results of a meta-analysis of phase III studies.
AB  - OBJECTIVE: The marketed doses of ibandronate, 150 mg once-monthly oral and 3 mg
      quarterly intravenous (IV) injection, produce greater increases in lumbar spine
      bone mineral density than treatment with the 2.5 mg oral daily dose. This meta
      analysis assessed whether these doses also reduce fracture risk relative to
      placebo. STUDY DESIGN AND METHODS: Individual patient data from the intent-to
      treat populations of the BONE, IV fracture prevention, MOBILE, and DIVA studies
      were grouped into three dose levels based on annual cumulative exposure (ACE),
      defined as the annual dose (mg) x bioavailability (0.6%, oral; 100%, IV) or
      placebo. Six key non-vertebral fractures (NVFs) (clavicle, humerus, wrist,
      pelvis, hip, and leg), all NVFs, and all clinical fractures were examined.
      RESULTS: This meta-analysis included 8710 patients. Cox proportional-hazards
      models estimated the adjusted relative risk (RR) for fracture with ibandronate
      versus placebo, and time to fracture was compared using log-rank tests. The high
      dose group (ACE > or = 10.8 mg) showed significant reductions in the adjusted RR
      of key NVFs (34.4%, p = 0.032), all NVFs (29.9%, p = 0.041), and clinical
      fractures (28.8%, p = 0.010) relative to placebo. The high-dose group also had
      significantly longer time to fracture versus placebo for key NVFs (p = 0.031),
      all NVFs (p = 0.025), and clinical fractures (p = 0.002). Study limitations
      included: not all studies were placebo-controlled; a limited number of baseline
      characteristics were available for multivariate analyses. CONCLUSION: Ibandronate
      at dose levels of ACE > or = 10.8 mg, which includes the marketed 150 mg once
      monthly oral and 3 mg quarterly IV injection regimens, may provide significant
      non-vertebral and clinical fracture efficacy.

PMID- 18047777
TI  - Cloning and characterization of a PI-like MADS-box gene in Phalaenopsis orchid.
AB  - The highly evolved flowers of orchids have colorful sepals and fused columns that
      offer an opportunity to discover new genes involved in floral development in
      monocotyledon species. In this investigation, we cloned and characterized the
      homologous PISTALLATA-like (PI-like) gene PhPI15 (Phalaenopsis PI STILLATA # 15),
      from the Phalaenopsis hybrid cultivar. The protein sequence encoded by PhPI15
      contains a typical PI-motif. Its sequence also formed a subclade with other
      monocot PI-type genes in phylogenetic analysis. Southern analysis showed that
      PhPI15 was present in the Phalaenopsis orchid genome as a single copy.
      Furthermore, it was expressed in all the whorls of the Phalaenopsis flower, while
      no expression was detected in vegetative organs. The flowers of transgenic
      tobacco plants ectopically expressing PhPI15 showed male-sterile phenotypes.
      Thus, as a Class-B MADS-box gene, PhPI15 specifies floral organ identity in
      orchids.

PMID- 18047778
TI  - Identification of proteins responsible for the development of adriamycin
      resistance in human gastric cancer cells using comparative proteomics analysis.
AB  - Resistance to anticancer drugs is a major obstacle in the effective treatment of
      tumors. To understand the mechanisms responsible for multidrug resistance (MDR),
      a proteomic approach was used to identify proteins that were expressed in
      different levels by the adriamycinresistant human gastric cancer cell line,
      SGC7901/ADR, and its parental cell line, SGC7901. Two-dimensional gel
      electrophoresis (2-DE) and image analysis was used to determine which protein
      spots were expressed in different levels by the two cell lines. These spots were
      then partially identified using ESI-Q-TOF mass spectrometry, and the differential
      expressional levels of the partially identified proteins were then determined by
      western blot analysis and real-time RT-PCR. Additionally, the association of
      Nucleophosmin (NPM1), a protein that was highly expressed by SGC7901/ADR, with
      MDR was analyzed using siRNA. As a result of this study, well-resolved,
      reproducible 2-DE patterns of SGC7901/ADR and SGC7901 were established, and 16
      proteins that may play a role in the development of thermoresistance were
      identified. Additionally, suppression of NPM1 expression was found to enhance
      adriamycin chemosensitivity in SGC7901/ADR. These results provide a fundamental
      basis for the elucidation of the molecular mechanism of MDR, which may assist in
      the treatment of gastric cancer.

PMID- 18047779
TI  - Molecular cloning and functional analysis of the gene encoding 3-hydroxy-3
      methylglutaryl coenzyme A reductase from hazel (Corylus avellana L. Gasaway).
AB  - The enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR; EC1.1.1.34) catalyzes
      the first committed step of isoprenoids biosynthesis in MVA pathway. Here we
      report for the first time the cloning and characterization of a full-length cDNA
      encoding HMGR (designated as CgHMGR, GenBank accession number EF206343) from
      hazel (Corylus avellana L. Gasaway), a taxol-producing plant species. The full
      length cDNA of CgHMGR was 2064 bp containing a 1704-bp ORF encoding 567 amino
      acids. Bioinformatic analyses revealed that the deduced CgHMGR had extensive
      homology with other plant HMGRs and contained two transmembrane domains and a
      catalytic domain. The predicted 3-D model of CgHMGR had a typical spatial
      structure of HMGRs. Southern blot analysis indicated that CgHMGR belonged to a
      small gene family. Expression analysis revealed that CgHMGR expressed high in
      roots, and low in leaves and stems, and the expression of CgHMGR could be up
      regulated by methyl jasmonate (MeJA). The functional color assay in Escherichia
      coli showed that CgHMGR could accelerate the biosynthesis of beta-carotene,
      indicating that CgHMGR encoded a functional protein. The cloning,
      characterization and functional analysis of CgHMGR gene will enable us to further
      understand the role of CgHMGR involved in taxol biosynthetic pathway in C.
      avellana at molecular level.

PMID- 18047780
TI  - Characterization of uridine-diphosphate dependent flavonoid glucosyltransferase
      from Oryza sativa.
AB  - We cloned a uridine-diphosphate dependent glycosyltransferase RUGT-10 from Oryza
      sativa. The recombinant enzyme was expressed by glutathione-S transferase gene
      fusion system in Escherichia coli. RUGT10 showed different regioselectivity
      depending on the structures of substrates (e.g. flavanone, flavonol, and
      flavone). Apparently, flavanone such as naringenin and eriodictyol gave one 7-O
      glucoside while flavone and flavonol gave more than two products with
      preferential glucosylation position of hydroxyl group at C-3 position.

PMID- 18047781
TI  - Cloning and characterization of a single chain antibody to glucose oxidase from a
      murine hybridoma.
AB  - Glucose oxidase (GOD) is an oxidoreductase catalyzing the reaction of glucose and
      oxygen to peroxide and gluconolacton (EC 1.1.3.4.). GOD is a widely used enzyme
      in biotechnology. Therefore the production of monoclonal antibodies and antibody
      fragments to GOD are of interest in bioanalytics and even tumor therapy. We
      describe here the generation of a panel of monoclonal antibodies to native and
      heat inactivated GOD. One of the hybridomas, E13BC8, was used for cloning of a
      single chain antibody (scFv). This scFv was expressed in Escherichia coli XL1
      blue with the help of the vector system pOPE101. The scFv was isolated from the
      periplasmic fraction and detected by western blotting. It reacts specifically
      with soluble active GOD but does not recognize denatured GOD adsorbed to the
      solid phase. The same binding properties were also found for the monoclonal
      antibody E13BC8.

PMID- 18047782
TI  - Antimicrobial activity of mupirocin, daptomycin, linezolid,
      quinupristin/dalfopristin and tigecycline against vancomycin-resistant
      enterococci (VRE) from clinical isolates in Korea (1998 and 2005).
AB  - It is a hot clinical issue whether newly approved antimicrobial agents such as
      daptomycin, linezolid, quinupristin/dalfopristin (synercid) and tigecycline are
      active enough to be used for infections caused by vancomycin resistant bacteria.
      We performed susceptibility tests for mupirocin, which is in widespread clinical
      use in Korea, and four new antimicrobials, daptomycin, linezolid,
      quinupristin/dalfopristin and tigecycline, against vancomycin-resistant
      Enterococcus faecalis and Enterococcus faecium isolated from Korean patients in
      1998 and 2005 to evaluate and compare the in vitro activity of these
      antimicrobials. Among these agents, quinupristin/dalfopristin, which is rarely
      used in hospitals in Korea, showed relatively high resistance to several
      vancomycin-resistant enterococci (VRE) isolated in 2005. Likewise, daptomycin,
      linezolid and tigecycline have not yet been in clinical use in Korea. However,
      our results showed that most of the 2005 VRE isolates were already resistant to
      linezolid and daptomycin (highest minimum inhibitory concentration (MIC) value
      >100 microg/ml). Compared with the other four antimicrobial agents tested in this
      study, tigecycline generally showed the greatest activity against VRE. However,
      four strains of 2005 isolates exhibited resistance against tigecycline (MIC >12.5
      microg/ml). Almost all VRE were resistant to mupirocin, whereas all E. faecium
      isolated in 1998 were inhibited at concentrations between 0.8 to approximately
      1.6 microg/ml. In conclusion, resistances to these new antimicrobial agents were
      exhibited in most of VRE strains even though these new antibiotics have been
      rarely used in Korean hospitals.

PMID- 18047783
TI  - Lipase inactive mutant of PLC-gamma1 regulates NGF-induced neurite outgrowth via
      enzymatic activity and regulation of cell cycle regulatory proteins.
AB  - Src homology (SH) domains of phospholipase C-gamma1 (PLC-gamma1) impair NGF
      mediated PC12 cells differentiation. However, whether the enzymatic activity is
      also implicated in this process remains elusive. Here, we report that the
      enzymatic activity of phospholipase C-gamma1 (PLC-gamma1) is at least partially
      involved to the blockage of neuronal differentiation via an abrogation of MAPK
      activation, as well as sustained Akt activation. By contrast, Overexpression of
      WT-PLC-gamma1 exhibited sustained NGF-induced MAPK activation, and triggered
      transient Akt activation resulting in profound inhibition of neurite outgrowth.
      However, lipase-inactive mutant (LIM) PLC-gamma1 cells fail to suppress neurite
      outgrowth, although it contains intact SH domains, specifically enhancing the
      expression of cyclin D1 and p21 proteins, which regulate the function of
      retinoblastoma Rb protein. These observations show that the lipase inactive
      mutant of PLC-gamma1 does not alter NGF-induced neuronal differentiation via
      enzymatic inability and the odulation of cell cycle regulatory proteins
      independent on SH3 domain.

PMID- 18047784
TI  - PD184352 releases the regular hypoxic reversible DNA replication arrest in T24
      cells.
AB  - The oxygen dependent regulation of DNA replication is an essential property of
      proliferating mammalian cells. In human T24 bladder cancer cells, several hours
      of hypoxia leads to reversible DNA replication arrest and re-entry of oxygen
      induces a burst of replication initiation. This short communication provides
      strong evidence that PD184352 initiates DNA replication in living hypoxic cells
      without elevating the oxygen level. PD184352 releases the regular hypoxic
      replicon arrest, however, at a low intensity compared to the effect of
      reoxygenation. Moreover, PD184352 shows no effect on normoxically incubated as
      well as reoxygenated T24 cells.

PMID- 18047785
TI  - RGS protein specificity towards Gq- and Gi/o-mediated ERK 1/2 and Akt activation,
      in vitro.
AB  - Extracellular Regulated Kinases (ERK) and Protein Kinase B (Akt) are
      intermediaries in relaying extracellular growth signals to intracellular targets.
      Each pathway can become activated upon stimulation of G protein-coupled receptors
      mediated by G(q) and G(i/o) proteins subjected to regulation by RGS proteins. The
      goal of the study was to delineate the specificity in which cardiac RGS proteins
      modulate G(q)and G(i/o)-induced ERK and Akt phosphorylation. To isolate G(q)- and
      G(i/o)-mediated effects, we exclusively expressed muscarinic M(2) or M(3)
      receptors in COS-7 cells. Western blot analyses demonstrated increase of
      phosphorylation of ERK 1.7-/3.3-fold and Akt 2.4-/6-fold in M(2)-/M(3)-
      expressing cells through carbachol stimulation. In co-expressions, M(3)/G(q)
      induced activation of Akt was exclusively blunted through RGS3s/RGS3, whereas
      activation of ERK was inhibited additionally through RGS2/RGS5. M(2)/G(i/o)
      induced Akt activation was inhibited by all RGS proteins tested. RGS2 had no
      effect on M(2)/G(i/o)-induced ERK activation. The high degree of specificity in
      RGS proteins-depending modulation of G(q)- and G(i/o)-mediated ERK and Akt
      activation in the muscarinic network cannot merely be attributed exclusively to
      RGS protein selectivity towards G(q) or G(i/o) proteins. Counter-regulatory
      mechanisms and inter-signaling cross-talk may alter the sensitivity of GPCR
      induced ERK and Akt activation to RGS protein regulation.

PMID- 18047786
TI  - Biosynthesis of isoprenoids: characterization of a functionally active
      recombinant 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase (IspD) from
      Mycobacterium tuberculosis H37Rv.
AB  - Tuberculosis, caused by Mycobacterium tuberculosis, continues to be one of the
      leading infectious diseases to humans. It is urgent to discover novel drug
      targets for the development of antitubercular agents. The 2-C-methyl-D-erythritol
      4-phosphate (MEP) pathway for isoprenoid biosynthesis has been considered as an
      attractive target for the discovery of novel antibiotics for its essentiality in
      bacteria and absence in mammals. MEP cytidyltransferase (IspD), the third-step
      enzyme of the pathway, catalyzes MEP and CTP to form 4-diphosphocytidyl-2-C
      methylerythritol (CDP-ME) and PPi. In the work, ispD gene from M. tuberculosis
      H37Rv (MtIspD) was cloned and expressed. With N-terminal fusion of a histidine
      tagged sequence, MtIspD could be purified to homogeneity by one-step nickel
      affinity chromatography. MtIspD exists as a homodimer with an apparent molecular
      mass of 52 kDa. Enzyme property analysis revealed that MtIspD has high
      specificity for pyrimidine bases and narrow divalent cation requirements, with
      maximal activity found in the presence of CTP and Mg(2+). The turnover number of
      MtIspD is 3.4 s(-1). The Km for MEP and CTP are 43 and 92 muM, respectively.
      Furthermore, MtIspD shows thermal instable above 50 degrees C. Circular dichroism
      spectra revealed that the alteration of tertiary conformation is closely related
      with sharp loss of enzyme activity at higher temperature. This study is expected
      to help better understand the features of IspD and provide useful information for
      the development of novel antibiotics to treat M. tuberculosis.

PMID- 18047787
TI  - Differential regulation of the promoter activity of the mouse UCP2 and UCP3 genes
      by MyoD and myogenin.
AB  - UCP2 and UCP3 are members of the uncoupling protein family, which may play roles
      in energy homeostasis. In order to determine the regulation of the predominant
      expression of UCP3 in skeletal muscle, the effects of differentiation and
      myogenic regulatory factors on the promoter activities of the mouse UCP2 and UCP3
      genes were studied. Reporter plasmids, containing approximately 3 kb of the 5'
      upstream region of the mouse UCP2 and UCP3 genes, were transfected into C2C12
      myoblasts, which were then induced to differentiate. Differentiation positively
      induced the reporter expression about 20-fold via the UCP3 promoter, but by only
      2-fold via the UCP2 promoter. C2C12 myoblasts were cotransfected with expression
      vectors for myogenin and/or MyoD as well as reporter constructs. The simultaneous
      expression of myogenin and MyoD caused an additional 20-fold increase in the
      reporter expression via the UCP3 promoter, but only a weak effect via the UCP2
      promoter. In L6 myoblasts, only MyoD activated the UCP3 promoter, but in 3T3-L1
      cells neither factor activated the UCP3 promoter, indicating that additional
      cofactors are required, which are present only in C2C12 myoblasts. The expression
      of UCP2 and UCP3 is differentially regulated during muscle differentiation due to
      the different responsiveness of their promoter regions to myogenin and MyoD.

PMID- 18047788
TI  - Protective effect of polysaccharide fractions from Radix A. sinensis against tert
      butylhydroperoxide induced oxidative injury in murine peritoneal macrophages.
AB  - Three Angelica sinensis polysaccharide fractions (APFs), named APF1, APF2 and
      APF3, were isolated and purified from Radix A. sinensis and their antioxidant
      activities were evaluated in isolated mouse peritoneal macrophages by
      pretreatment with APFs before exposure to 0.2 mM tertbutylhydroperoxide (t-BHP).
      The results showed that pretreatment of the macrophages with APFs as low as 10
      microg/ml could significantly enhance t-BHP-decreased cell survival,
      intracellular glutathione (GSH) content and superoxide dismutase (SOD) activity,
      and also inhibited t-BHP-increased lactate dehydrogenase (LDH) leakage and
      malondialdehyde (MDA) formation (p < 0.05), and APF3 was the most active
      fraction, followed by APF2 and APF1 in decreasing order. Furthermore, we found
      for the first time that the bound-protein in APF3 was associated closely with the
      protective effects and the polysaccharide inhibited the excess NO release from t
      BHP-activated macrophages to protect host cells.

PMID- 18047789
TI  - Detection of antistaphylococcal and toxic compounds by biological assay systems
      developed with a reporter Staphylococcus aureus strain harboring a heat inducible
      promoter - lacZ transcriptional fusion.
AB  - Previously it was reported that promoter of groES-groEL operon of Staphylococcus
      aureus is induced by various cell-wall active antibiotics. In order to exploit
      the above promoter for identifying novel antistaphylococcal drugs, we have cloned
      the promoter containing region (P(g)) of groES-groEL operon of S. aureus Newman
      and found that the above promoter is induced by sublethal concentrations of many
      antibiotics including cell-wall active antibiotics. A reporter S. aureus RN4220
      strain (designated SAU006) was constructed by inserting the P(g)-lacZ
      transcriptional fusion into its chromosome. Agarose-based assay developed with
      SAU006 shows that P(g) in single-copy is also induced distinctly by different
      classes of antibiotics. Data indicate that ciprofloxacin, rifampicin, ampicillin,
      and cephalothin are strong inducers, whereas, tetracycline, streptomycin and
      vancomycin induce the above promoter weakly. Sublethal concentrations of
      ciprofloxacin and ampicilin even have induced P(g) efficiently in microtiter
      plate grown SAU006. Additional studies show for the first time that above
      promoter is also induced weakly by arsenate salt and hydrogen peroxide. Taken
      together, we suggest that our simple and sensitive assay systems with SAU006
      could be utilized for screening and detecting not only novel antistaphylococcal
      compounds but also different toxic chemicals.

PMID- 18047790
TI  - Induction of megakaryocytic differentiation in chronic myelogenous leukemia cell
      K562 by 3-hydrogenkwadaphnin.
AB  - 3-Hydrogenkwadaphnin (3-HK) is a daphnane-type diterpene ester isolated from
      Dendrostellera lessertii (Thymelaeaceae) with high differentiation and apoptotic
      potency in leukemic cells without any measurable adverse effects on normal cells
      (Moosavi et al., 2005b). In this study, we report that 3-HK (12 nM) has the
      ability to cease proliferation, induce differentiation and apoptosis in chronic
      myelogenous leukemia (CML) K562 cell line. The treated cells lost erythroid
      properties and differentiated along the megakaryocytic lineage based on the
      morphological features apparent after Wright-Giemsa staining, DNA content
      analysis and the expression of cell surface marker glycoprotein IIb as analyzed
      by flow cytometry. Moreover, using Hoechst 33258 and Annexin V double staining
      indicated the occurrence of apoptosis among the treated cells. On the other hand,
      restoration of the depleted GTP pool size by exogenous addition of guanosine (50
      microM) reduced the effect of the drug regarding the extent of differentiation
      while no further enhancement of 3-HK effect was obtained by addition of exogenous
      hypoxanthine (100 microM). These interesting results necessitate further
      investigation regarding the mechanism of action of this unique anti-leukemic
      agent.

PMID- 18047791
TI  - Characterization of a stress-responsive ankyrin repeat-containing zinc finger
      protein of Capsicum annuum (CaKR1).
AB  - We isolated many genes induced from pepper cDNA microarray data following their
      infection with the soybean pustule pathogen Xanthomonas axonopodis pv. glycines
      8ra. A full-length cDNA clone of the Capsicum annuum ankyrin-repeat domain
      C(3)H(1) zinc finger protein (CaKR1) was identified in a chili pepper using the
      expressed sequence tag (EST) database. The deduced amino acid sequence of CaKR1
      showed a significant sequence similarity (46%) to the ankyrin-repeat protein in
      very diverse family of proteins of Arabidopsis. The gene was induced in response
      to various biotic and abiotic stresses in the pepper leaves, as well as by an
      incompatible pathogen, such as salicylic acid (SA) and ethephon. CaKR1 expression
      was highest in the root and flower, and its expression was induced by treatment
      with agents such as NaCl and methyl viologen, as well as by cold stresses. These
      results showed that CaKR1 fusion with soluble, modified green fluorescent protein
      (smGFP) was localized to the cytosol in Arabidopsis protoplasts, suggesting that
      CaKR1 might be involved in responses to both biotic and abiotic stresses in
      pepper plants.

PMID- 18047792
TI  - Isolation and characterization of two Korean mistletoe lectins.
AB  - Two isolectins (KML-IIU and the KML-IIL) were individually isolated from the
      previously reported Korean mistletoe lectin, KML-C, by using an immunoaffinity
      column. Molecular weights of the KML-IIU and the KML-IIL were 64 kDa and 60 kDa
      respectively. Both of the lectins were composed of heterogeneous A and B subunits
      linked with a disulfide bond, and showed the same carbohydrate-binding
      specificities for Gal and GalNAc. However, they are different not only in
      biophysical properties (glycosylation and amino acid compositions) but also
      bioactivities (cell killing and cytokine induction). The KML-IIL showed 17-145
      times stronger in cytotoxicities to various human and mouse cancer cell lines
      than the KML-IIU. The KML-IIL also induced TNF-alpha secretion from mouse
      peritoneal macrophages 4.5 times better than the KML-IIU. The results
      demonstrated isolectins in Korean mistletoe were varied in bioactivities and the
      KML-IIL may be developed as an anti-cancer agent.

PMID- 18047793
TI  - The important anti-apoptotic role and its regulation mechanism of PTTG1 in UV
      induced apoptosis.
AB  - Pituitary tumor transforming gene (PTTG1) is widely detected in many tumors.
      Increasing evidence reveals that PTTG1 is associated with cell proliferation,
      cellular transformation and apoptosis. However, the functions of PTTG1,
      especially its role in DNA damage-induced apoptosis, remain largely unclear. In
      this report, we used UV irradiation to induce apoptosis in HeLa cells to examine
      the role of PTTG1 in UV-induced apoptosis by RNAi-mediated knockdown and
      overexpression of PTTG1. RNAi-mediated knockdown of PTTG1 expression increased
      and overexpression of PTTG1 decreased the UV-induced apoptosis. Furthermore, UV
      irradiation decreased PTTG1 mRNA and protein expression. These effects were found
      to be mediated by JNK pathway. Therefore, PTTG1 had an important anti-apoptotic
      role in UV-induced apoptosis and this role was mediated by JNK pathway. These
      results may provide important information for understanding the exact role and
      the regulation mechanism of PTTG1 in UV-induced apoptosis.

PMID- 18047794
TI  - SEPT12 interacts with SEPT6 and this interaction alters the filament structure of
      SEPT6 in Hela cells.
AB  - Septins are a family of conserved cytoskeletal GTPase forming heteropolymeric
      filamentous structure in interphase cells, however, the mechanism of assembly are
      largely unknown. Here we described the characterization of SEPT12, sharing
      closest homology to SEPT3 and SEPT9. It was revealed that subcellular
      localization of SEPT12 varied at interphase and mitotic phase. While SEPT12
      formed filamentous structures at interphase, it was localized to the central
      spindle and to midbody during anaphase and cytokinesis, respectively. In
      addition, we found that SEPT12 can interact with SEPT6 in vitro and in vivo, and
      this interaction was independent of the coiled coil domain of SEPT6. Further, co
      expression of SEPT12 altered the filamentous structure of SEPT6 in Hela cells.
      Therefore, our result showed that the interaction between different septins may
      affect the septin filament structure.

PMID- 18047795
TI  - Induction of growth hormone release by glycyrrhizae radix on rat.
AB  - Induction of growth hormone (GH) by Glycyrrhizae Radix (GR), one of the most
      popular herbal medicine, and its major ingredients were studied in rat pituitary
      cells in vitro and in vivo assay. The MeOH extract and the n-hexane (HX) fraction
      of GR induced rat GH (rGH) release up to 1.89 times (0.34 +/- 0.04 nM) and 4.59
      times (0.83 +/- 0.03 nM), compared to the basal level (p < 0.05). Among many
      ingredients isolated and purified from GR both glycyrrhetinic acid and
      glycyrrhizin induced significantly rGH release compared to the control (p <
      0.05). After an intravenous injection of rat growth hormone releasing hormone
      (rGHRH) (10 microg/kg) as positive control, in SD rats, Tmax of plasma rGH level
      was 10 min, C(max) was 3.84 +/- 0.01 nM (n = 3), and enhanced plasma rGH level
      returned to the baseline in 90 min. Both AUC(0-90) (area under the curve) of
      plasma rGH level after HX fraction and that after rGHRH administration were
      increased significantly from the basal level, respectively (p < 0.01). In
      conclusions, HX fraction is the most active fraction of MeOH extract of GR in rGH
      induction.

PMID- 18047797
TI  - Overexpression and purification of PreS region of hepatitis B virus antigenic
      surface protein adr subtype in Escherichia coli.
AB  - PreS domain of Hepatitis B virus (HBV) surface antigen is a good candidate for an
      effective vaccine as it activates both B and T cells besides binding to
      hepatocytes. This report deals with overexpression and purification of adr
      subtype of surface antigen that is more prevalent in Pakistan. PreS region,
      comprising 119 aa preS1 region plus a 55 aa preS2 region plus 11 aa from the N
      terminal S region, was inserted in pET21a+ vector, cloned in E. coli DH5alpha
      cells and expressed in E. coli BL21 codon+ cells. The conditions for over
      expression were optimized using different concentrations of IPTG (0.01-5 mM), and
      incubating the cells at different temperatures (23-41 degrees C) for different
      durations (0-6 h). The cells were grown under the given optimized conditions (0.5
      mM IPTG concentration at 37 degrees C for 4 h), lysed by sonication and the
      protein was purified by ion exchange chromatography. On the average, 24.5 mg of
      recombinant protein was purified per liter of culture. The purified protein was
      later lyophilized and stored at -80 degrees.

PMID- 18047798
TI  - Cell cycle regulation and induction of apoptosis by beta-carotene in U937 and HL
      60 leukemia cells.
AB  - In this communication, we report the efficacy of beta-carotene towards
      differentiation and apoptosis of leukemia cells. Dose (20 microM) and time
      dependence (12 h) tests of beta- carotene showed a higher magnitude of decrease
      (significance p < 0.05) in cell numbers and cell viability in HL-60 cells than
      U937 cells but not normal cell like Peripheral blood mononuclear cell (PBMC).
      Microscopical observation of beta-carotene treated cells showed a distinct
      pattern of morphological abnormalities with inclusion of apoptotic bodies in both
      leukemia cell lines. When cells were treated with 20 microM of beta-carotene,
      total genomic DNA showed a fragmentation pattern and this pattern was clear in HL
      60 than U937 cells. Both the cell lines, on treatment with beta- carotene, showed
      a clear shift in G(1) phase of the cell cycle. In addition the study also
      revealed anti-oxidant properties of beta-carotene since there was reduction in
      relative fluorescent when treated than the control at lower concentration.
      Collectively this study shows the dual phenomenon of apoptosis and
      differentiation of leukemia cells on treatment with beta-carotene.

PMID- 18047799
TI  - Induction of growth hormone release by dioscin from Dioscorea batatas DECNE.
AB  - In this study, dioscin was isolated from Dioscoreae Rhizoma (DR), which is the
      rhizome of Dioscorea batatas D(ECNE). that inhabits broad areas of Korea and
      Japan. To determine whether dioscin induced growth hormone (GH) release, we
      evaluated its induction effects on GH release both in vitro and in vivo. The 70%
      methanol extract of DR, and its n-hexane and n-BuOH fractions, induced rat GH
      (rGH) release in rat pituitary cells 10-fold, 8-fold, and 5- fold higher than the
      control (0.36 +/- 0.02 nM), respectively (p < 0.05 each). The dioscin-induced rGH
      release of the cells was concentration-dependent and its ED(50) was 1.14 x 10(-5)
      M. Within 90 minutes after intravenous administration of 10 microg/kg (p < 0.05
      at t(max)), dioscin caused the greatest increase in rGH concentration (C(max)) in
      the rat plasma (34.16 +/- 14.10 ng/ml) (n = 4), which was twice as high as the
      control group (12.88 +/- 3.29 ng/ml) (n = 27).

PMID- 18047796
TI  - Differentially expressed genes under cold acclimation in Physcomitrella patens.
AB  - Cold acclimation improves freezing tolerance in plants. In higher plants, many
      advances have been made toward identifying the signaling and regulatory pathways
      that direct the low-temperature stress response; however, similar insights have
      not yet been gained for simple nonvascular plants, such as bryophytes. To
      elucidate the pathways that regulate cold acclimation in bryophytes, we used two
      PCR-based differential screening techniques, cDNA amplified fragment length
      polymorphism (cDNA-AFLP) and suppression subtractive hybridization (SSH), to
      isolate 510 ESTs that are differentially expressed during cold acclimation in
      Physcomitrella patens. We used realtime RT-PCR to further analyze expression of
      29 of these transcripts during cold acclimation. Our results show that cold
      acclimation in the bryophyte Physcomitrella patens is not only largely similar to
      higher plants but also displays distinct differences, suggests significant
      alteration during the evolution of land plants.

PMID- 18047800
TI  - Construction and expression of mutant cDNAs responsible for genetic polymorphism
      in aldehyde oxidase in Donryu strain rats.
AB  - We demonstrated the genetic polymorphism of aldehyde oxidase (AO) in Donryu
      strain rats: the ultrarapid metabolizer (UM) with nucleotide mutation of (377G,
      2604C) coding for amino acid substitution of (110Gly, 852Val), extensive
      metabolizer (EM) with (377G/A, 2604C/T) coding for (110Gly/Ser, 852Val/Ala), and
      poor metabolizer (PM) with (377A, 2604T) coding for (110Ser, 852Ala),
      respectively. The results suggested that 377G > A and/or 2604C > T should be
      responsible for the genetic polymorphism. In this study, we constructed an E.
      coli expression system of four types of AO cDNA including Mut-1 with (377G,
      2604T) and Mut-2 with (377A, 2604C) as well as naturally existing nucleotide
      sequences of UM and PM in order to clarify which one is responsible for the
      polymorphism. Mut-1 and Mut-2 showed almost the same high and low activity as
      that of the UM and PM groups, respectively. Thus, the expression study of mutant
      AO cDNA directly revealed that the nucleotide substitution of 377G > A, but not
      that of 2604C > T, will play a critical role in the genetic polymorphism of AO in
      Donryu strain rats. The reason amino acid substitution will cause genetic
      polymorphism in AO activity was discussed.

PMID- 18047801
TI  - Evidence of tandem repeat and extra thiol-groups resulted in the polymeric
      formation of bovine haptoglobin: a unique structure of Hp 2-2 phenotype.
AB  - Human plasma Hp is classified as 1-1, 2-1, and 2-2. They are inherited from two
      alleles Hp 1 and Hp 2, but there is only Hp 1 in almost all the animal species.
      Hp 2-2 molecule is extremely large and heterogeneous associated with the
      development of inflammatory-related diseases. In this study, we expressed entire
      bovine Hp in E. coli as a alphabeta linear form. Interestingly, the antibodies
      prepared against this form could recognize the subunit of native Hp. In stead of
      a complicated column method, the antibody was able to isolate bovine Hp via
      immunoaffinity and gel-filtration columns. The isolated Hp is polymeric
      containing two major molecular forms (660 and 730 kDa). Their size and hemoglobin
      binding complex are significantly larger than that of human Hp 2-2. The amino
      acid sequence deducted from the nucleotide sequence is similar to human Hp 2
      containing a tandem repeat over the alpha chain. Thus, the Hp 2 allele is not
      unique in human. We also found that there is one additional -SH group (Cys-97) in
      bovine alpha chain with a total of 8 -SH groups, which may be responsible for the
      overall polymeric structure that is markedly different from human Hp 2-2. The
      significance of the finding and its relationship to structural evolution are also
      discussed.

PMID- 18047802
TI  - Anti-oxidative effect of a protein from Cajanus indicus L against acetaminophen
      induced hepato-nephro toxicity.
AB  - Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study
      was undertaken to investigate the protective effect of a 43 kDa protein isolated
      from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal
      toxicity. Male albino mice were treated with the protein for 4 days
      (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of
      acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes
      (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine
      and blood urea nitrogen were measured in the experimental sera. Intracellular
      reactive oxygen species production and total antioxidant activity were also
      determined from acetaminophen and protein treated hepatocytes. Indices of
      different antioxidant enzymes (namely, superoxide dismutase, catalase,
      glutathione-S-transferase) as well as lipid peroxidation end-products and
      glutathione were determined in both liver and kidney homogenates. In addition,
      Cytochrome P450 activity was also measured from liver microsomes. Finally,
      histopathological studies were performed from liver sections of control,
      acetaminophen-treated and protein pre- and post-treated (along with
      acetaminophen) mice. Administration of acetaminophen increased all the serum
      markers and creatinine levels in mice sera along with the enhancement of hepatic
      and renal lipid peroxidation. Besides, application of acetaminophen to
      hepatocytes increased reactive oxygen species production and reduced the total
      antioxidant activity of the treated hepatocytes. It also reduced the levels of
      antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In
      addition, acetaminophen enhanced the cytochrome P450 activity of liver
      microsomes. Treatment with the protein significantly reversed these changes to
      almost normal. Apart from these, histopathological changes also revealed the
      protective nature of the protein against acetaminophen induced necrotic damage of
      the liver tissues. Results suggest that the protein protects hepatic and renal
      tissues against oxidative damages and could be used as an effective protector
      against acetaminophen induced hepato-nephrotoxicity.

PMID- 18047803
TI  - Characterization of peptide deformylase2 from B. cereus.
AB  - Peptide deformylase (PDF) is a metalloenzyme that removes the N-terminal formyl
      groups from newly synthesized proteins. It is essential for bacterial survival,
      and is therefore-considered as a potential target for antimicrobial chemotherapy.
      However, some bacteria including medically relevant pathogens possess two or more
      def-like genes. Here we have examined two PDFs from Bacillus cereus. The two
      share only 32% sequence identity and the crystal structures show overall
      similarity with PDF2 having a longer C-terminus. However, there are differences
      at the two active sites, and these differences appear to contribute to the
      activity difference seen between the two. BcPDF2 is found as a dimer in the
      crystal form with two additional actinonin bound at that interface.

PMID- 18047804
TI  - Proteomic analysis of O-GlcNAc modifications derived from streptozotocin and
      glucosamine induced beta-cell apoptosis.
AB  - The post-translational modifications of Ser and Thr residues by O-linked beta-N
      acetylglucosamine (O-GlcNAc), i.e., O-GlcNAcylation, is considered a key means of
      regulating signaling, in a manner analogous to protein phosphorylation.
      Furthermore, it has been suggested that the increased flux of glucose through the
      hexosamine biosynthetic pathway (HBP) stimulates O-GlcNAcylation, and that this
      may be responsible for many of the manifestations of type 2 diabetes mellitus. To
      determine whether excessive O-GlcNAcylation of target proteins results in
      pancreatic beta cell dysfunction, we increased nucleocytoplasmic protein O
      GlcNAcylation levels in beta cells by exposing them to streptozotocin and/or
      glucosamine. Streptozotocin and glucosamine co-treatment increased OGlcNAcylated
      proteomic patterns as assessed by immunoblotting, and these increases in nuclear
      and cytoplasmic protein O-GlcNAcylations were accompanied by impaired insulin
      secretion and enhanced apoptosis in pancreatic beta cells. This observed beta
      cell dysfunction prompted us to examine Akt and Bcl-2 family member proteins to
      determine which proteins are O-GlcNAcylated under conditions of high HBP
      throughput, and how these proteins are associated with beta cell apoptosis.
      Eventually, we identified ten new O-GlcNAcylated proteins that were expressed
      during beta cell apoptosis, and analyzed the functional implications of these
      proteins in relation to pancreatic beta cell dysfunction.

PMID- 18047805
TI  - Disulfiram suppresses invasive ability of osteosarcoma cells via the inhibition
      of MMP-2 and MMP-9 expression.
AB  - Cancer cells, characterized by local invasion and distant metastasis, are very
      much dependent on the extracellular matrix. The expression of matrix
      metalloproteinases (MMPs) has been implicated in the invasion and metastasis of
      cancer cells. In this study, we reported the effects of disulfiram, a clinically
      used anti-alcoholism drug, on tumor invasion suppression, as well as its effects
      on the activity of MMP-2 and MMP-9 in human osteosarcoma cells (U2OS). Disulfiram
      has been used for alcohol aversion therapy. However, recent reports have shown
      that disulfiram may have potential in the treatment of human cancers. Herewith,
      we showed that the anti-tumor effects of disulfiram, in an invasion assay using
      U2OS cells and that disulfiram has a type IV collagenase inhibitory activity that
      inhibits expression of genes and proteins responsible for both cell and non-cell
      mediated invasion on pathways. In conclusion, disulfiram inhibited expression of
      MMP-2 and MMP-9 and it regulated the invasion of human osteosarcoma cells. These
      observations raise the possibility of disulfiram being used clinical for the
      inhibition of cancer invasion.

PMID- 18047806
TI  - Inhibitory properties of nerve-specific human glutamate dehydrogenase isozyme by
      chloroquine.
AB  - Human glutamate dehydrogenase exists in hGDH1 (housekeeping isozyme) and in hGDH2
      (nerve-specific isozyme), which differ markedly in their allosteric regulation.
      In the nervous system, GDH is enriched in astrocytes and is important for
      recycling glutamate, a major excitatory neurotransmitter during
      neurotransmission. Chloroquine has been known to be a potent inhibitor of house
      keeping GDH1 in permeabilized liver and kidney-cortex of rabbit. However, the
      effects of chloroquine on nerve-specific GDH2 have not been reported yet. In the
      present study, we have investigated the effects of chloroquine on hGDH2 at
      various conditions and showed that chloroquine could inhibit the activity of
      hGDH2 at dose-dependent manner. Studies of the chloroquine inhibition on enzyme
      activity revealed that hGDH2 was relatively less sensitive to chloroquine
      inhibition than house-keeping hGDH1. Incubation of hGDH2 was uncompetitive with
      respect of NADH and non-competitive with respect of 2-oxoglutarate. The
      inhibitory effect of chloroquine on hGDH2 was abolished, although in part, by the
      presence of ADP and L-leucine, whereas GTP did not change the sensitivity to
      chloroquine inhibition. Our results show a possibility that chloroquine may be
      used in regulating GDH activity and subsequently glutamate concentration in the
      central nervous system.

PMID- 18047807
TI  - AtHAP3b plays a crucial role in the regulation of flowering time in Arabidopsis
      during osmotic stress.
AB  - The HAP complex has been found in many eukaryotic organisms. HAP recognizes the
      CCAAT box present in the promoters of 30% of all eukaryotic genes. The HAP
      complex consists of three subunits--HAP2, HAP3 and HAP5. In this paper, we report
      the biological function of the AtHAP3b gene that encodes one of the HAP3 subunits
      in Arabidopsis. Compared with wild-type plants, hap3b-1 and hap3b-2 mutants
      exhibited a delayed flowering time under long-day photoperiod conditions.
      Moreover, the transcription levels of FT were substantially lower in the mutants
      than in the wild-type plants. These results imply that AtHAP3b may function in
      the control of flowering time by regulating the expression of FT in Arabidopsis.
      In a subsequent study, AtHAP3b was found to be induced by osmotic stress. Under
      osmotic stress conditions, the hap3b-1 and hap3b-2 mutants flowered considerably
      later than the wild-type plants. These results suggest that the AtHAP3b gene
      plays more important roles in the control of lowering under osmotic stress in
      Arabidopsis.

PMID- 18047808
TI  - Cell selectivity of an antimicrobial peptide melittin diastereomer with D-amino
      acid in the leucine zipper sequence.
AB  - Melittin (ME), a linear 26-residue non-cell-selective antimicrobial peptide,
      displays strong lytic activity against bacterial and human red blood cells. To
      design ME analogue with improved cell selectivity, we synthesized a melittin
      diastereomer (ME-D) with D-amino acid in the leucine zipper sequence (Leu-6, Lue
      13 and Ile-20). Compared to ME, ME-D exhibited the same or 2-fold higher
      antibacterial activity but 8-fold less hemolytic activity. Circular dichroism
      analysis revealed that ME-D has much less alpha-helical content in alpha-helical
      content in the presence of zwitterionic EYPC/cholesterol (10 : 1, w/w) liposomes
      compared to negatively charged EYPE/EYPG (7 : 3, w/w) liposomes. The blue shift
      of the fluorescence emission maximum of ME-D in zwitterionic EYPC/ cholesterol
      (10 : 1, w/w) liposomes was much smaller than in negatively charged EYPE/EYPG (7
      : 3, w/w) liposomes. These results suggested that the improvement in therapeutic
      index/cell selectivity of ME-D is correlated with its less permeability to
      zwitterionic membranes.

PMID- 18047809
TI  - Ectopic expression of mitochondria endonuclease Pnu1p from Schizosaccharomyces
      pombe induces cell death of the yeast.
AB  - Endonuclease G (EndoG) is a mitochondrial non-specific nuclease that is highly
      conserved among the eukaryotes. Although the precise role of EndoG in
      mitochondria is not yet known, the enzyme is released from the mitochondria and
      digests nuclear DNA during apoptosis in mammalian cells. Schizosaccharomyces
      pombe has an EndoG homolog Pnu1p (previously named SpNuc1) that is produced as a
      precursor protein with a mitochondrial targeting sequence. During the sorting
      into mitochondria the signal sequence is cleaved to yield the functionally active
      endonuclease. From the analogy to EndoG, active extramitochondrial Pnu1p may
      trigger cell killing by degrading nuclear DNA. Here, we tested this possibility
      by expressing a truncated Pnu1p lacking the signal sequence in the
      extramitochondrial region of pnu1-deleted cells. The truncated Pnu1p was
      localized in the cytosol and nuclei of yeast cells. And ectopic expression of
      active Pnu1p led to cell death with fragmentation of nuclear DNA. This suggests
      that the Pnu1p is possibly involved in a certain type of yeast cell death via DNA
      fragmentation. Although expression of human Bak in S. pombe was lethal, Pnu1p
      nuclease is not necessary for hBak-induced cell death.

PMID- 18047810
TI  - Is Helicobacter pylori responsible for autoimmune diseases? That is the question.

PMID- 18047811
TI  - Hypersensitivity to Vespula and Polistes: can we tell the primary sensitization
      from the clinical history?
AB  - OBJECTIVE: To study the relationship between the primary sensitization to wasp
      venoms and the geographical and seasonal circumstances of the anaphylaxis-induced
      sting. METHODS: We performed a retrospective review of 115 patients (age 10-80)
      who suffered a systemic reaction to a wasp sting. Season and type of locality
      (urban or rural) at the moment of the sting were recorded. Serum specific IgE
      levels to venoms from Vespula and Polistes were measured, and a primary
      sensitization was determined to whichever genus of wasp for which the highest
      class of specific IgE was observed. The primary sensitization in relation to the
      type of locality and the season was assessed using the chi-square test. RESULTS:
      Most reactions occurred in urban areas (67.8 %), and in the summer season (63.4
      %). Most patients were sensitized to Vespula venom (94.8 %). Primary
      sensitization was to Vespula in 56.5 %, to Polistes in 10.4 %, and undetermined
      in 33 %. The distribution of geographical areas did not show significant
      differences in relation to primary sensitization (p > 0.05). Most patients with
      primary sensitization to Vespula suffered the anaphylaxis-induced sting after the
      spring season, with a statistically significant result (p < 0.05). CONCLUSION: In
      our population, the probability of Vespula sting is higher than Polistes sting
      when the reaction occurs after spring. This finding can help us to identify the
      responsible vespid when the diagnostic tests do not provide an accurate result.

PMID- 18047812
TI  - Risk factors of developing asthma in children with recurrent wheezing in the
      first three years of life.
AB  - INTRODUCTION: recurrent wheezing is a common problem during the first years of
      life, but it is still difficult to identify which of these children may develop
      asthma in the future. OBJECTIVES: To study risk factors of developing asthma in a
      group of patients with frequent wheezing during the first three years of life.
      MATERIAL AND METHODS: A prospective study was performed of a group of 60
      patients, aged below three, referred to our Hospital for recurrent wheezing. Age,
      sex, parental and personal history of atopy, clinical features, laboratory tests,
      evolution and response to treatment were analyzed. RESULTS: 60 patients were
      enrolled in study. Most of children were boys and have had the first episode of
      wheezing after the 6 months of life. 63 % had personal history of atopy and 55 %
      parental history of allergy. The group of atopic children had more wheezing
      exacerbations and worse evolution than the group of non atopic. They also had
      more treatment necessities. CONCLUSIONS: The identification of young children at
      high risk of developing asthma could permit an early intervention before
      irreversible changes in the airway appeared.

PMID- 18047814
TI  - Pregnancy outcomes in women using inhaled fluticasone during pregnancy: a case
      series.
AB  - BACKGROUND: The aim of the study was to report the maternal and fetal outcomes of
      women with respiratory illnesses who were treated with inhaled fluticasone during
      pregnancy. MATERIAL AND METHODS: We identified 12 cases treated with inhaled
      fluticasone during pregnancy out of women who received obstetric and teratogen
      risk evaluation at the Korean Motherisk Program. A detailed medical and obstetric
      history was obtained and cases were followed-up until either spontaneous or
      voluntary pregnancy termination or delivery occurred. RESULTS: None of the
      participants had any obstetric complication. However, in addition to fluticasone,
      most of the 12 cases were simultaneously exposed to a variety of medications.
      There were 3 abortions (one spontaneous and 2 requested by the patients arguing
      personal reasons). Live born babies without any evidence of major congenital
      malformations included 8 singleton babies and 2 twins. Of them, 3 babies were
      born prematurely. CONCLUSIONS: Our results are in agreement with previous large
      studies where no increased rate of adverse outcomes was reported with the use of
      inhaled corticosteroids during pregnancy.

PMID- 18047813
TI  - Serum leptin levels and lipid profiles in patients with allergic rhinitis and
      mild asthma.
AB  - BACKGROUND: Despite improved understanding of the pathophysiology of allergic
      rhinitis and asthma, the effect of serum leptin level is still controversial.
      Only a few studies have been performed to investigate the serum leptin levels in
      allergic rhinitis and asthma, and contradictory results have been observed.
      OBJECTIVE: We aimed to investigate the association between leptin, lipid profiles
      and allergic rhinitis and mild asthma, and to determine whether inhaled and/or
      intranasal steroids affect the leptin levels. PATIENTS AND METHODS: We studied 43
      patients with allergic rhinitis (10 of with mild asthma) (mean age 29.81, range
      18-45 yr) and 32 volunteers as a control group (mean age 30.53, range 20-45 yr).
      RESULTS: Serum leptin levels in patients were 8.49 +/- 10.76 microg/ml, and did
      not differ from volunteers 5.42 +/- 6.63 microg/ml. (p > 0.05). We found a direct
      link between increased body mass index (BMI) and serum leptin levels (p = 0.008).
      No association was seen between leptin and triglyceride, HDL-cholesterol, VLDL
      cholesterol, eosinophil, total IgE (p > 0.05); except for total cholesterol and
      LDL-cholesterol (p < 0.05). Although, no correlation between allergic rhinitis
      and mild asthma and serum level of leptin was shown, these parameters and age
      correlations were stronger in female than in male (p = 0.39 for male and p =
      0.011 for female), and also found direct link between increased BMI and sex and
      patients group (p = 0.008 for male and p = 0.0001 for female). We also determined
      that there was no effect of inhaled and/or intranasal steroids statistically on
      serum leptin levels. CONCLUSION: Our data demonstrate that the serum levels of
      leptin and lipid profiles on allergic rhinitis and mild asthma were not different
      than those in controls.

PMID- 18047815
TI  - Correlation of environmental mite levels and the symptoms of allergic rhinitis
      regarding the efficacy of preventive education.
AB  - Allergic rhinitis is still a commonly investigated disease all over the world.
      Allergens are usually in the nature of glycoprotein or protein which interact
      with antibodies resulting in the formation of specific Ig E in the body 1. It is
      presumed that some environmental factors play an important role in their clinics.
      In allergic rhinitis, symptoms usually occur after the interaction of nasal
      mucosa with allergens. Allergens may be indoors, outdoors or in both
      environments. House-dust contains most of the indoor allergens. Mites are the
      most egregious allergen in house dust. D. pteronyssinus is commonly seen in
      European countries, D. farinae is mostly seen in North America. House-dust mites
      play an important role in allergic sensitization of individuals in Turkey.
      Perennial allergic rhinitis is a common chronic disorder that results most
      frequently from sensitivity to house-dust mites. National and international
      guidelines for the management of allergic rhinitis recommend that house and dust
      mite avoidance measures be considered for all patients with house-dust mite
      provoked rhinitis. Symptoms of allergic rhinitis are related to the environmental
      mite level in which patients live. The aim of this study is to show the
      relationship between mite levels and symptoms of allergic rhinitis diagnosed
      patients and the change of mite levels in the environment after appropriate
      education.

PMID- 18047816
TI  - Prevalence of symptoms of asthma, rhinitis, and atopic eczema among adolescents
      living in urban and rural areas in different regions of Brazil.
AB  - BACKGROUND: In Brazil, studies evaluating the prevalence of asthma and allergic
      diseases among children living in rural area compared to urban area are rare.
      Some authors identified as risk factors for higher prevalence of current wheezing
      to have a family history of asthma, to have contact with pets, and being student
      in an urban school. The International Study of Asthma and Allergies in Childhood
      (ISAAC) phase 3 has shown higher prevalence of wheezing, nasal symptoms and
      cutaneous rash in the last 12 months in centers from Northern (N) and
      Northeastern (NE) regions of Brazil. OBJECTIVE: To evaluate if adolescents with
      similar genetic background, living in a rural area are protected against the
      development of symptoms of asthma, rhinitis, and atopic eczema when compared to
      those living in an urban area in the same region of the country. SUBJECTS AND
      METHOD: Adolescents (13-14 year-old) living in Caruaru (Pernambuco) and in Santa
      Maria (Rio Grande do Sul) were enrolled in this study (2002-2003). The
      adolescents filled in the ISAAC written questionnaire (WQ), previously translated
      and validated to the Brazilian culture (30-32). Data obtained were transcribed
      manually into a database (Epi-Info) supplied by ISAAC's coordinators and were
      statistically analyzed by the SSPS-12 software. RESULTS: The prevalence of asthma
      related symptoms were higher among those adolescents living in the urban centers
      in comparison to the rural ones. These differences were significant for wheezy
      ever, wheezy in the last 12 months, asthma ever, and wheezy with exercise in
      Caruaru and for wheezy ever and asthma ever, in Santa Maria. Comparing urban
      areas, the prevalence of asthma related symptoms in Caruaru was higher than in
      Santa Maria, except for wheezy ever and wheezy with exercise. The opposite was
      observed comparing rural areas: the prevalence of asthma (except for nocturnal
      cough) was higher in Santa Maria despite lesser severity of symptoms in this
      city.

PMID- 18047817
TI  - Interactions between genes and the environment. Epigenetics in allergy.
AB  - Epigenetics is defined as those inheritable changes occurring in gene expression,
      without actual modification in the genic DNA sequence. Epigenetic factors are
      chemically stable, potentially reversible, and can be modulated or induced by
      environmental factors. In the case of allergic disease, epigenetics could explain
      not only the discordances observed between monozygous twins but also phenomena
      such as incomplete penetrance, variable expression, gender and progenitor
      effects, and sporadic cases. In this sense, the hypothesis of hygiene is of great
      relevance in that it integrates genetic and epidemiological data in the context
      of environmental exposures. Among the different epigenetic factors, mention must
      be made of DNA methylation, covalent histone modifications, and other mechanisms
      that include different protein complexes and RNA-mediated modifications. The
      regulatory effect of these phenomena upon immune response has important
      implications for allergic diseases. At present, different lines of
      pharmacological research are being conducted, based on the modulation of
      epigenetic factors, modifying expression of the genes that encode for proteins
      implicated in allergic processes. Among such modulators, mention can be made of
      antisense oligonucleotides, ribozymes and interference RNA. The applications of
      epigenetics to the diagnosis and treatment of allergic disorders offer a very
      promising future of this specialty.

PMID- 18047818
TI  - Immunotherapy with Alternaria alternata: present and future.
AB  - The prevalence of fungal allergies is greater than previously believed;
      consequently, such processes have been underestimated as potential causes of
      respiratory tract disease. Most patients sensitized to fungi exhibit perennial
      symptoms, though their intensity increases in the summer and autumn months. Skin
      reactions to the antigens of Alternaria alternata are associated with a high risk
      of allergic respiratory conditions in the presence of spores of this fungus 
      fundamentally in children and young adults- with a special form of presentation
      as life-threatening asthma. Very few controlled studies have examined the
      efficacy and safety of fungal extract immunotherapy -the main problem being the
      lack of standardized extracts for the diagnosis and treatment of such patients.
      In the year 2005 a tolerance study was made in children in relation to a depot
      extract containing the predominant antigen of Alternaria, with two different
      regimens (short and cluster). Tolerance was found to be good, with a 0.95 %
      incidence of local reactions and a 0.95 % incidence of grade 2 systemic
      reactions. Few studies involving sublingual immunotherapy have been conducted to
      date.

PMID- 18047819
TI  - Efficient bibliographic searches on allergology using PubMed.
AB  - INTRODUCTION: PubMed is the most important of the non-specialized databases on
      biomedical literature. International and quickly updated is elaborated by the
      American Government and contains only information about papers published in
      scientific journal/s. Although it can be used as an unique Data Base, as a matter
      of fact is the addition of several subgroups (among them MEDLINE) that can be
      searched simultaneously. OBJECTIVES: To present the main characteristics of
      PubMed, as well as the most important procedures of search, for obtaining
      efficient results in searches on allergology. CHARACTERISTICS AND SEARCH
      PROCEDURES: PubMed is elaborated by the American Administration, that condition
      the character of the registered papers, 90 % of them are written in English in
      American (50 %) or British (20 %) Journals. Because of this, the information for
      certain specialties or countries must be obtained from other sources. This paper
      shows how PubMed allows to search in natural language due to the Automatic Term
      Mapping that links terms from the natural language with the descriptors producing
      searches with a higher sensitivity although with a low specificity. Nevertheless
      the MeSH (Medical Subject Headings) thesaurus allows to translate those terms
      from the natural language to the equivalent descriptor, as well as to make
      queries in the PubMed's documental language with a high specificity but with
      lower sensitivity than the natural language. The use of union (OR), intersection
      (AND) and exclusion (NOT) operators, as well as tags, such as delimiters of the
      search fields, allows to increase the specificity of the results. Similar results
      may be obtained with the use of Limits. Searches done using Clinical Queries are
      very interesting due to their direct clinical application and because allow to
      find systematic reviews, metaanalysis or clinically oriented papers (treatment,
      diagnostic, etiology, prognosis or clinical prediction guides) on the area of
      interest. Other procedures such as the Index, History of searches, and the
      widening of the selection using Related Articles and the storing of separate
      results in the Clipboard to be kept by the user, are presented in this paper.

PMID- 18047820
TI  - Fragrances as a cause of food allergy.
AB  - A 34-year-old woman referred episodes of gastrointestinal disorders and sometimes
      angioedema of the lips which appeared within 2 hours from the ingestion of packed
      food like biscuits, cereals or fruit juice. A patch test with the standard
      European series and with food preservatives was positive for fragrances mix. The
      avoidance of packed food labelled as containing flavours among the ingredients
      caused the disappearance of the above reported symptoms.

PMID- 18047821
TI  - Not all ACE inhibitor related angioedema is always evident: a case which is
      misdiagnosed as panic attack and speech disorder.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are the most common medications
      responsible for angioedema. Angioedema is a potentially life threatening
      conditions especially in geriatric age patients that they have take a several
      medications include ACE inhibitors and non steroidal anti inflammatory drugs. We
      present a case an ACE inhibitor induced angioedema that confused many clinical
      events.

PMID- 18047822
TI  - Codeine challenge in chronic urticaria patients.

PMID- 18047823
TI  - Site-directed circular dichroism of proteins: 1Lb bands of Trp resolve position
      specific features in tear lipocalin.
AB  - The absorption spectra of N-acetyl-L-tryptophanamide in various solvents were
      resolved into the sums of the (1)L(a) and (1)L(b) components. The relative
      intensities of the 0-0 transitions of the (1)L(b) bands correlate linearly with
      the solvent polarity values (E(T)(N)). A novel strategy that uses a set of the
      experimental (1)L(b) bands was employed to resolve the near-UV circular dichroism
      (CD) spectra of tryptophanyl residues. Resolved spectral parameters from the
      single-tryptophan mutants of tear lipocalin (TL), F99W and Y87W, corroborate the
      fluorescence and structural data of TL. Analysis of the (1)L(b) bands of the Trp
      CD spectra in proteins is a valuable tool to obtain the local features. The
      dimethyl sulfoxide (DMSO)-like (1)L(b) band of Trp CD spectra may be used as a
      "fingerprint" to identify the tryptophanyl side chains in situations where the
      benzene rings of Trp have van der Waals interactions with the side chains of its
      nearest neighbor. In addition, the signs and intensities of the components hold
      information about the side chain conformations and dynamics in proteins. Combined
      with Trp mutagenesis, this method, which we call site-directed circular
      dichroism, is broadly applicable to various proteins to obtain the position
      specific data.

PMID- 18047824
TI  - Initial synthesis and characterization of an immobilized heat shock protein 90
      column for online determination of binding affinities.
AB  - Heat shock protein 90 alpha (Hsp90alpha) was immobilized on aminopropyl silica
      via the N terminus to create the Hsp90alpha(NT) column or via the C terminus to
      create the Hsp90alpha(CT) column. Binding to the exposed C terminus on the
      Hsp90alpha(NT) column was characterized using frontal chromatography and the C
      terminus ligands coumermycin A(1) (CA1) and novobiocin (NOVO). The calculated
      K(d) values were 220+/-110 nM (CA1) and 100+/-20 nM (NOVO). Nonlinear
      chromatography was used to determine the association and dissociation rate
      constants associated with the NOVO-Hsp90alpha complex: 22.2+/-8.8 microM(-1) s(
      1) and 2.7+/-0.6s(-1), respectively. Binding to the exposed N terminus on the
      Hsp90alpha(CT) column was characterized using frontal chromatography. The K(d)
      values of the N-terminus ligands geldanamycin (GM, 90+/-50 nM), 17-allylamino-17
      demethoxygeldanamycin (17-AAG, 210+/-50 nM), and radicicol (RAD, 20+/-9 nM) were
      consistent with previously reported values. The effect of the immobilization on
      ATPase activity was investigated through the determination of IC(50) values for
      inhibition of ATPase activity on the Hsp90alpha(CT) column. The IC(50) for GM was
      2.80+/-0.18 microM, and the relative IC(50) values were 17-AAG>GM>RAD, in
      agreement with previously reported values and indicating that immobilization had
      not affected ATPase activity or sensitivity to inhibition.

PMID- 18047825
TI  - Staurosporine-based binding assay for testing the affinity of compounds to
      protein kinases.
AB  - Staurosporine is a broad-spectrum inhibitor of both tyrosine and serine/threonine
      protein kinases. Excitation of staurosporine and its analogues at 296 nm results
      in major emission bands centered at 378 and 396 nm. The intensity of the emission
      bands is enhanced on binding to the adenosine triphosphate (ATP) site of many
      protein kinases. This property was used to develop a competitive displacement
      assay for evaluating the binding affinity of small molecules to protein kinases.
      The assay was validated in both cuvette and plate formats for several
      phosphorylated and non-phosphorylated protein kinases. The throughput of the
      assay is high enough to be used in drug discovery for screening as well as lead
      optimization.

PMID- 18047826
TI  - Quantitative effects of allosteric ligands and mutations on conformational
      equilibria in Salmonella typhimurium tryptophan synthase.
AB  - Allosteric communications are important in coordination of the reactions in the
      tryptophan (Trp) synthase alpha2beta2 multienzyme complex. We have measured the
      conformational equilibria of l-Ser and l-Trp complexes, using absorption and
      fluorescence spectrophotometry with hydrostatic pressure equilibrium
      perturbation. The effects of monovalent cations, disodium alpha-glycerophosphate
      (Na2GP), indoleacetylglycine (IAG), and benzimidazole (BZI), as well as of
      betaE109D and betaD305A mutations, on K(eq) for the conformational equilibria
      were determined. The l-Ser external aldimine-aminoacrylate equilibrium
      (K(eq)=[external aldimine]/[aminoacrylate]) has the largest value with Na+
      (0.12), followed by K+ (0.04), Li+ (7.6 x 10(-4)), Rb+ (4.3 x 10(-4)), NH4+ (2.3
      x 10(-4)), no cation (2.0 x 10(-4)) and Cs+ (1.6x10(-5)). alpha-Site ligands,
      Na(2)GP and IAG, have modest 3- to 40-fold effects on K(eq) in the direction of
      aminoacrylate, but BZI in the presence of Na+ gives a low value of K(eq)
      comparable to that obtained with Cs(+). There is no additivity of free energy for
      Na2GP and BZI, suggesting a common pathway for allosteric communications for both
      ligands. The values of DeltaV(o) range from -126 mL/mol for the Na+ complex to 
      204 mL/mol for the Na+ complex with BZI. The betaD305A mutation changes the K(eq)
      by a factor of at least 10(5) (26.7kJ/mol) and nearly abolishes allosteric
      communications. There are also dramatic decreases in the magnitude of both
      DeltaV(o) and DeltaS for the l-Ser external aldimine-aminoacrylate equilibrium
      for betaD305A Trp synthase, consistent with a large decrease in solvation
      accompanying the conformational change in betaD305A Trp synthase relative to wild
      type Trp synthase. The betaE109D mutation has more modest but significant effects
      on K(eq), which differ with the ligand, ranging from 40-fold for GP to 2200-fold
      for BZI, even though betaGlu-109 is not directly involved in allosteric
      communications. The effect of GP on the external aldimine-quinonoid intermediate
      equilibrium of the Trp synthase-l-Trp complex is similar to that of GP on the Trp
      synthase-l-Ser external aldimine-aminoacrylate equilibrium. These results have
      allowed a quantitative comparison of the allosteric effects of ligand and
      mutations in Trp synthase. These allosteric effects are finely tuned to control
      the synthesis of l-Trp without resulting in substrate or product inhibition.

PMID- 18047827
TI  - Control of cell respiration by nitric oxide in Ataxia Telangiectasia
      lymphoblastoid cells.
AB  - Ataxia Telangiectasia (AT) patients are particularly sensitive to oxidative
      nitrosative stress. Nitric oxide (NO) controls mitochondrial respiration via the
      reversible inhibition of complex IV. The mitochondrial response to NO of AT
      lymphoblastoid cells was investigated. Cells isolated from three patients and
      three intrafamilial healthy controls were selected showing within each group a
      normal diploid karyotype and homogeneous telomere length. Different complex IV NO
      inhibition patterns were induced by varying the electron flux through the
      respiratory chain, using exogenous cell membrane permeable electron donors. Under
      conditions of high electron flux the mitochondrial NO inhibition of respiration
      was greater in AT than in control cells (P< or =0.05). This property appears
      peculiar to AT, and correlates well to the higher concentration of cytochrome c
      detected in the AT cells. This finding is discussed on the basis of the proposed
      mechanism of reaction of NO with complex IV. It is suggested that the peculiar
      response of AT mitochondria to NO stress may be relevant to the mitochondrial
      metabolism of AT patients.

PMID- 18047828
TI  - A structural investigation of complex I and I+III2 supercomplex from Zea mays at
      11-13 A resolution: assignment of the carbonic anhydrase domain and evidence for
      structural heterogeneity within complex I.
AB  - The projection structures of complex I and the I+III2 supercomplex from the C4
      plant Zea mays were determined by electron microscopy and single particle image
      analysis to a resolution of up to 11 A. Maize complex I has a typical L-shape.
      Additionally, it has a large hydrophilic extra-domain attached to the centre of
      the membrane arm on its matrix-exposed side, which previously was described for
      Arabidopsis and which was reported to include carbonic anhydrase subunits. A
      comparison with the X-ray structure of homotrimeric gamma-carbonic anhydrase from
      the archaebacterium Methanosarcina thermophila indicates that this domain is also
      composed of a trimer. Mass spectrometry analyses allowed to identify two
      different carbonic anhydrase isoforms, suggesting that the gamma-carbonic
      anhydrase domain of maize complex I most likely is a heterotrimer. Statistical
      analysis indicates that the maize complex I structure is heterogeneous: a less
      abundant "type II" particle has a 15 A shorter membrane arm and an additional
      small protrusion on the intermembrane-side of the membrane arm if compared to the
      more abundant "type I" particle. The I+III2 supercomplex was found to be a rigid
      structure which did not break down into subcomplexes at the interface between the
      hydrophilic and the hydrophobic arms of complex I. The complex I moiety of the
      supercomplex appears to be only of "type I". This would mean that the "type II"
      particles are not involved in the supercomplex formation and, hence, could have a
      different physiological role.

PMID- 18047829
TI  - A trimeric building block model for Cry toxins in vitro ion channel formation.
AB  - The crystal (Cry) insecticidal toxins, or delta-endotoxins, are lethal to a wide
      variety of insect larvae, and are therefore very important in insect control.
      Toxicity has been explained by formation of transmembrane oligomeric pores or ion
      channels and, more recently, by the ability of the monomeric toxin to subvert
      cellular signaling pathways. The structure, topology, and precise role of the
      putative pore in toxicity are not known. However, in vitro biophysical studies
      suggest that helices alpha4 and alpha5 in domain I insert into the lipid bilayer
      as an alpha-helical hairpin. Mutagenesis studies have assigned an important role
      to alpha5 in maintaining oligomerization, and to alpha4 in channel formation. To
      detect the possible homo-oligomerizing tendencies of these two helices, we have
      used the evolutionary conservation data contained in sixteen Cry homologs in
      order to filter non-native interactions found during a global conformational
      search. No conserved homo-oligomer was found for alpha4, but a right handed
      trimeric alpha5 model was present in the simulations of all Cry sequences. We
      propose a model for Cry toxin oligomerization based on sequence analysis and
      available mutagenesis data.

PMID- 18047830
TI  - High definition profiling of autoantibodies to glutamic acid decarboxylases
      GAD65/GAD67 in stiff-person syndrome.
AB  - Highly reliable biomarkers for the diagnosis of neurological diseases are not
      widely available. Here we evaluated a luciferase immunoprecipitation technology
      (LIPS) for the diagnosis of a CNS autoimmune disorder, stiff-person syndrome
      (SPS). Analysis by LIPS of 40 sera samples from SPS and control subjects for anti
      GAD65 antibodies revealed dramatic titer differences allowing diagnosis of SPS
      with 100% sensitivity and 100% specificity. Anti-GAD65 antibody titers of SPS
      were segregated from controls with values greater than 23 standard deviations
      above the control subject mean. By analyzing patient antibody responses directly
      to GAD65 sub-fragments, the central region containing the decarboxylase catalytic
      domain was highly immunoreactive with all of the SPS sera, while the N- and C
      terminal regions showed lower antibody titers and only reacted with subsets of
      SPS sera. Additional profiling revealed that some SPS patients showed
      autoantibodies against GAD67 and tyrosine hydroxylase, but no significant
      immunoreactivity was detected with cysteine sulfinic acid decarboxylase or GABA
      transaminase. This study validates LIPS as a robust method to interrogate
      autoantibodies for the diagnosis of SPS and potentially other neurological
      diseases.

PMID- 18047831
TI  - Which skeletal myoblasts and how to be transplanted for cardiac repair?
AB  - Clinical efficacy of skeletal myoblast (skMb) transplantation is controversial
      whether this treatment produces beneficial outcome in patients with dilated
      cardiomyopathy (DCM). Based on immunological tolerance between wild-type and DCM
      hamsters with the deletion of delta-sarcoglycan (SG) gene, skMb engraftment in TO
      2 myocardium (3x10(5) cells in approximately 100mg heart) was verified by the
      donor-specific expression of delta-SG transgene constitutively produced
      throughout myogenesis. At 5 weeks after the transplantation, the cell rates
      expressing fast-myosin heavy chain (MHC) exceeded slow-MHC in delta-SG(+) cells.
      Fifteen weeks after (corresponding to approximately 12 years in humans), fast
      MHC(+) cells nullified, but the delta-SG(+) and slow MHC(+) cell number remained
      unaltered. These skMbs fused with host cardiomyocytes via connexin-43 and
      intercalated disc, modestly improving the hemodynamics without arrhythmia, when
      engrafted skMbs were sparsely disseminated in autopsied myocardium. These results
      provide us evidence that disseminating delivery of slow-MHC(+) myoblasts is
      promising for repairing DCM heart using histocompatible skeletal myoblasts in
      future.

PMID- 18047832
TI  - Skeletal muscle-derived progenitors capable of differentiating into
      cardiomyocytes proliferate through myostatin-independent TGF-beta family
      signaling.
AB  - The existence of skeletal muscle-derived stem cells (MDSCs) has been suggested in
      mammals; however, the signaling pathways controlling MDSC proliferation remain
      largely unknown. Here we report the isolation of myosphere-derived progenitor
      cells (MDPCs) that can give rise to beating cardiomyocytes from adult skeletal
      muscle. We identified that follistatin, an antagonist of TGF-beta family members,
      was predominantly expressed in MDPCs, whereas myostatin was mainly expressed in
      myogenic cells and mature skeletal muscle. Although follistatin enhanced the
      replicative growth of MDPCs through Smad2/3 inactivation and cell cycle
      progression, disruption of myostatin did not increase the MDPC proliferation. By
      contrast, inhibition of activin A (ActA) or growth differentiation factor 11
      (GDF11) signaling dramatically increased MDPC proliferation via down-regulation
      of p21 and increases in the levels of cdk2/4 and cyclin D1. Thus, follistatin may
      be an effective progenitor-enhancing agent neutralizing ActA and GDF11 signaling
      to regulate the growth of MDPCs in skeletal muscle.

PMID- 18047833
TI  - Bone marrow long label-retaining cells reside in the sinusoidal hypoxic niche.
AB  - In response to changing signals, quiescent hematopoietic stem cells (HSCs) can be
      induced to an activated cycling state and provide multi-lineage hematopoietic
      cells to the whole body via blood vessels. However, the precise localization of
      quiescent HSCs in bone marrow microenvironment is not fully characterized. Here,
      we performed whole-mount immunostaining of bone marrow and found that BrdU label
      retaining cells (LRCs) definitively reside in the sinusoidal hypoxic zone distant
      from the "vascular niche". Although LRCs expressed very low level of a well-known
      HSC marker, c-kit in normal circumstances, myeloablation by 5-FU treatment caused
      LRCs to abundantly express c-kit and proliferate actively. These results
      demonstrate that bone marrow LRCs reside in the sinusoidal hypoxic niche, and
      function as a regenerative cell pool of HSCs.

PMID- 18047834
TI  - CISD1 codifies a mitochondrial protein upregulated by the CFTR channel.
AB  - Cystic fibrosis (CF) is an autosomic recessive disease caused by mutations in the
      CFTR chloride channel, which indirectly affect the expression of a net of genes.
      Here we describe a new CFTR-dependent gene, CISD1, encoding for the first member
      of a family of proteins possessing a CDGSH signature. CISD1 mRNA is down
      regulated in cystic fibrosis cells, and restored in the same cells ectopically
      expressing wt-CFTR (CFDE and CFDE/6RepCFTR; IB3-1 and S9 cells). Inhibition of
      CFTR chloride transport activity by using glibenclamide (50muM, 24h) or CFTR(inh)
      172 (5muM, 24h), resulted in the down-regulation of CISD1 mRNA, and CFTR
      stimulation with cAMP/isoproterenol/IBMX upregulated its expression. As predicted
      by PSORT II, a CISD1-GFP chimera was found to be located into mitochondria,
      suggesting a possible role in the function/regulation of mitochondrial activity,
      in agreement with earlier observations of a possible mitochondrial failure in
      cystic fibrosis.

PMID- 18047835
TI  - The effects of cyclin-dependent kinase inhibitors on adipogenic differentiation
      of human mesenchymal stem cells.
AB  - The molecular mechanisms that couple growth arrest and cell differentiation were
      examined during adipogenesis. Here, to understand the cyclin-dependent kinase
      inhibitor (CKI) genes involved in the progression of adipogenic differentiation,
      we examined changes in the protein and mRNA expression levels of CKI genes in
      vitro. During the onset of growth arrest associated with adipogenic
      differentiation, two independent families of CKI genes, p27Kip1 and p18INK4c,
      were significantly increased. The expressions of p27Kip1 and p18INK4c, regulated
      at the level of protein and mRNA accumulation, were directly coupled to
      adipogenic differentiation. This finding was supported by the inhibition of
      adipogenic differentiation caused by short interfering RNA (siRNA). In this
      study, we investigated the regulatory effects of transforming growth factor beta
      1 (TGFbeta-1) on CKI genes involved in adipogenic differentiation of bone marrow
      derived human mesenchymal stem cells (hMSCs). Only the up-regulation of p18INK4c
      during adipogenic differentiation, and not that of the p27Kip1 gene was prevented
      by treatment with TGFbeta-1, one of the factors that inhibit adipogenesis in
      vitro. This finding indicates a close correlation between adipogenic
      differentiation and p18INK4c induction in hMSCs. Thus, these data demonstrate a
      role for the differentiation-dependent cascade expression of cyclin-dependent
      kinase inhibitors in regulating adipogenic differentiation, thereby providing a
      molecular mechanism that couples growth arrest and differentiation.

PMID- 18047836
TI  - Severity dependent increases in circulating cardiac troponin I and MMP-9
      concentrations after experimental acute pulmonary thromboembolism.
AB  - BACKGROUND: Making the diagnosis of acute pulmonary thromboembolism (APT) and
      assessing its severity is very challenging. While cardiac troponin I (cTnI)
      concentrations are promising in risk stratification, no previous study has
      examined whether there is a linear relation between cTnI concentrations and the
      severity of APT. Moreover, matrix metalloproteinases (MMPs) are involved in the
      pathophysiology of APT. However, it is unknown whether the increases in MMP
      concentrations after APT reflect the severity of this condition. We examined
      whether the circulating concentrations of these biomarkers increase in proportion
      to the severity of experimental APT induced in anesthetized dogs. METHODS: APT
      was induced with autologous blood clots (saline, 1, 3, or 5 ml/kg) injected into
      the right atrium. Hemodynamic evaluations were carried out for 120 min. Gelatin
      zymography of MMP-2 and MMP-9 from plasma samples were performed and serum cTnI
      concentrations were determined at baseline and 120 min after APT. RESULTS: While
      no significant increases in pro-MMP-2 concentrations were found after APT, pro
      MMP-9 concentrations increased by 80% only after 5 ml/kg of clot embolization.
      Serum cTnI and plasma pro-MMP-9 concentrations correlated positively with
      pulmonary vascular resistance (P=0.007 and rs=0.833 for troponin I, and P=0.034
      and rs=0.684 for pro-MMP-9) and with pulmonary artery pressure (P=0.005 and
      rs=0.610 for troponin I, and P=0.022 and rs=0.720 for pro-MMP-9). CONCLUSIONS:
      Circulating cTnI and pro-MMP-9 increase in proportion to the severity of APT,
      although the increases in plasma pro-MMP-9 are less clear with less severe APT.
      These findings may be relevant for clinical APT.

PMID- 18047837
TI  - Use of 2 years of patient data to estimate intra-laboratory total imprecision of
      HbA(1c) measured by multiple HPLC analyzers.
AB  - BACKGROUND: Analytic imprecision is used to assess the acceptability of HbA(1c)
      methods performed on a single analyzer. When multiple analyzers are used
      interchangeably in a laboratory, the analytic imprecision is usually increased
      and can obscure the detection of a genuine HbA(1c) trend or result in an
      artefactual patient trend. We have estimated the imprecision of HbA(1c) testing
      of patient specimens by three HbA(1c) analyzers independent of reference sample
      analysis. METHODS: Over 2 years, approximately 150,000 HbA(1c) measurements were
      obtained from any one of three different Bio-Rad VARIANT II HPLC analyzers
      operated in a large reference laboratory. We tabulated the HbA(1c) measurements
      of paired intra-patient blood samples drawn within 30 days of each other. We
      calculated the standard deviations of duplicates (SDD) of the intra-patient
      HbA(1c) pairs grouped by the following time intervals: 0-3 days, 4-6 days, 7-9
      days, 28-30 days. The SDDs were then regressed against time with extrapolation to
      zero time representing the random analytic error. RESULTS: At a mean HbA(1c) of
      7.16%, the total analytic imprecision (coefficient of variation [CV]) is 3.6%.
      CONCLUSIONS: This variation is remarkably low, given that the HbA(1c)
      measurements were obtained over a 2-year period on any one of three analyzers and
      the long-term within-analyzer CV was usually 2.3-3.1% as assessed by reference
      control analysis. This approach could be extended to all HbA(1c) analyzers since
      unlike reference control statistics, the patient-derived random error should
      allow easy comparison of analytic imprecision among different analytical systems.

PMID- 18047838
TI  - Epac signaling pathway involves STEF, a guanine nucleotide exchange factor for
      Rac, to regulate APP processing.
AB  - The amyloid precursor protein (APP) is a key protein involved in the development
      of Alzheimer's disease. We previously identified a signal transduction secretory
      pathway in which the small G protein Rac sets downstream of the cAMP/Epac/Rap1
      signalling cascade regulating the alpha cleavage of APP [Maillet, M. et al.
      (2003) Crosstalk between Rap and Rac regulates secretion of sAPP alpha. Nat. Cell
      Biol. 5, 633-639]. We now report that Rap1 can physically and specifically
      associate with the guanine nucleotide exchange factor (GEF) STEF through its TSS
      region. A deleted TSS domain of STEF cells fails to activate Rac1 and
      dramatically decreases secretion of the non-amyloidogenic soluble form of APP
      (sAPP alpha) induced by the cAMP-binding protein Epac. Altogether, our data show
      that upon Epac activation, Rap1 recruits STEF through its TSS region and
      activates Rac1, which mediates APP processing.

PMID- 18047839
TI  - On the origin of synonymous codon usage divergence between thermophilic and
      mesophilic prokaryotes.
AB  - Synonymous codon usage analysis between thermophilic and mesophilic prokaryotes
      has gained wide attention in recent years. Although it is known that thermophilic
      and mesophilic prokaryotes use different subset of synonymous codons, no reason
      for this difference is known so far. In the present communication, by analyzing a
      large number of thermophilic and mesophilic prokaryotes, we provide evidence that
      bias in the selection of synonymous codons between thermophilic and mesophilic
      prokaryotes is related to differential folding pattern of mRNA secondary
      structures. Moreover, we observe that error-minimizing property has significant
      influence in differentiating the synonymous codon usage between thermophilic and
      mesophilic prokaryotes. Biological implications of these results are discussed.

PMID- 18047840
TI  - Glutaredoxins and thioredoxins in plants.
AB  - During the 70s and 80s two plant thioredoxin systems were identified. The
      chloroplastic system is composed of a ferredoxin-dependent thioredoxin, with two
      thioredoxin types (m and f) regulating the activity of enzymes implicated in
      photosynthetic carbon assimilation. In the cytosol of heterotrophic tissues, an
      NADP dependent thioredoxin reductase and a thioredoxin (h) were identified. The
      first plant glutaredoxin was only identified later, in 1994. Our view of plant
      thioredoxins and glutaredoxins was profoundly modified by the sequencing programs
      which revealed an unexpected number of genes encoding not only the previously
      identified disulfide reductases, but also numerous new types. At the same time it
      became clear that plant genomes encode chloroplastic, cytosolic and mitochondrial
      peroxiredoxins, suggesting a major role for redoxins in anti-oxidant defense.
      Efficient proteomics approaches were developed allowing the characterization of
      numerous thioredoxin target proteins. They are implicated in different aspects of
      plant life including development and adaptation to environmental changes and
      stresses. The most important challenge for the next years will probably be to
      identify in planta which redoxin reduces which target, a question which remains
      unsolved due to the low specificities of redoxins in vitro and the numerous
      redundancies which in most cases mask the phenotype of redoxin mutants.

PMID- 18047842
TI  - Macrophage apolipoprotein-E knockdown modulates caspase-3 activation without
      altering sensitivity to apoptosis.
AB  - Apolipoprotein-E (apoE) expression may be associated with apoptosis resistance.
      Since macrophages constitutively synthesize apoE we speculated that this may
      contribute to apoptosis resistance. Using siRNA, human monocyte derived
      macrophage (hMDM) apoE mRNA and protein was reduced by 97% and 61%, respectively.
      ApoE knockdown increased staurosporine-induced caspase-3 activation by 78%
      without altering cell survival or apoptosis as assessed by TUNEL analysis and
      morphological changes. This result was confirmed using murine bone marrow derived
      macrophages (mBMDM) from apoE null and wild type mice. In these experiments,
      staurosporine-induced caspase-3 activation was increased by 49% in apoE null
      compared to wild type mBMDM and this was not associated with differences in TUNEL
      signal, annexin-V binding or DNA fragmentation. ApoE is also important for
      cholesterol transport and macrophage cholesterol can regulate apoptosis.
      Knockdown of hMDM apoE inhibited basal cholesterol efflux by 20% without altering
      apolipoprotein-AI mediated cholesterol efflux over 24 h. Similarly, in apoE null
      mBMDM a non significant trend for a 16% reduction in basal cholesterol efflux was
      observed as compared to wild type mBMDM. In conclusion, apoE expression modulates
      capase-3 activity, but this has no significant impact on sensitivity to apoptosis
      and only a moderate impact on basal cholesterol efflux.

PMID- 18047841
TI  - The Galalpha1,3Galbeta1,4GlcNAc-R (alpha-Gal) epitope: a carbohydrate of unique
      evolution and clinical relevance.
AB  - In 1985, we reported that a naturally occurring human antibody (anti-Gal),
      produced as the most abundant antibody (1% of immunoglobulins) throughout the
      life of all individuals, recognizes a carbohydrate epitope Galalpha1-3Galbeta1
      4GlcNAc-R (the alpha-gal epitope). Since that time, an extensive literature has
      developed on discoveries related to the alpha-gal epitope and the anti-Gal
      antibody, including the barrier they form in xenotransplantation and their
      reciprocity in mammalian evolution. This review covers these topics and new
      avenues of clinical importance related to this unique antigen/antibody system
      (alpha-gal epitope/anti-Gal) in improving the efficacy of viral vaccines and in
      immunotherapy against cancer.

PMID- 18047843
TI  - Interactions of nitrosylhemoglobin and carboxyhemoglobin with erythrocyte.
AB  - Nitrosylhemoglobin (HbFe(II)NO) has been detected in vivo, and its role in NO
      transport and preservation has been discussed. To gain insight into the potential
      role of HbFe(II)NO, we performed in vitro experiments to determine the effect of
      oxygenated red blood cells (RBCs) on the dissociation of cell-free HbFe(II)NO,
      using carboxyhemoglobin (HbFe(II)CO) as a comparison. Results show that the
      apparent half-life of the cell-free HbFe(II)CO was reduced significantly in the
      presence of RBCs at 1% hematocrit. In contrast, RBC did not change the apparent
      half-life of extracellular HbFe(II)NO, but caused a shift in the HbFe(II)NO
      dissociation product from methemoglobin (metHbFe(III)) to oxyhemoglobin
      (HbFe(II)O(2)). Extracellular hemoglobin was able to extract CO from HbFe(II)CO
      containing RBC, but not NO from HbFe(II)NO-containing RBC. Although these results
      appear to suggest some unusual interactions between HbFe(II)NO and RBC, the data
      are explainable by simple HbFe(II)NO dissociation and hemoglobin oxidation with
      known rate constants. A kinetic model consisting of these reactions shows that
      (i) deoxyhemoglobin is an intermediate in the reaction of HbFe(II)NO oxidation to
      metHbFe(III), (ii) the rate-limiting step of HbFe(II)NO decay is the dissociation
      of NO from HbFe(II)NO, (iii) the magnitude of NO diffusion rate constant into RBC
      is estimated to be approximately 10(4)M(-1)s(-1), consistent with previous
      results determined from a competition assay, and (iv) no additional chemical
      reactions are required to explain these data.

PMID- 18047844
TI  - Clostridium scindens baiCD and baiH genes encode stereo-specific 7alpha/7beta
      hydroxy-3-oxo-delta4-cholenoic acid oxidoreductases.
AB  - Secondary bile acids, formed by intestinal bacteria, are suggested to play a
      significant role in cancers of the gastrointestinal tract in humans. Bile acid
      7alpha/beta-dehydroxylation is carried out by a few species of intestinal
      clostridia which harbor a multi-gene bile acid inducible (bai) operon. Several
      genes encoding enzymes in this pathway have been cloned and characterized.
      However, no gene product(s) has yet been assigned to the production of 3-oxo
      Delta4-cholenoic acid intermediates of cholic acid (CA), chenodeoxycholic acid
      (CDCA) or ursodeoxycholic acid (UDCA). We previously reported that the baiH gene
      encodes an NADH:flavin oxidoreductase (NADH:FOR); however, the role of this
      protein in bile acid 7-dehydroxylation is unclear. Homology searches and
      secondary structural alignments suggest this protein to be similar to
      flavoproteins which reduce alpha/beta-unsaturated carbonyl compounds. The baiH
      gene product was expressed in Escherichia coli, purified and discovered to be a
      stereo-specific NAD(H)-dependent 7beta-hydroxy-3-oxo-Delta4-cholenoic acid
      oxidoreductase. Additionally, high sequence similarity between the baiH and baiCD
      gene products suggests the baiCD gene may encode a 3-oxo-Delta4-cholenoic acid
      oxidoreductase specific for CDCA and CA. We tested this hypothesis using cell
      extracts prepared from E. coli overexpressing the baiCD gene and discovered that
      it encodes a stereo-specific NAD(H)-dependent 7alpha-hydroxy-3-oxo-Delta4
      cholenoic acid oxidoreductase.

PMID- 18047846
TI  - Regulatory considerations in the development of high-density lipoprotein
      therapies.
AB  - The development of high-density lipoprotein (HDL) therapies has experienced a
      recent setback with the notable termination of clinical development of
      torcetrapib, a cholesteryl ester transfer protein inhibitor. Potentially because
      of off-target actions of torcetrapib, surrogate biomarkers intended to elucidate
      the impact of the drug on atherosclerosis provided an uninterpretable picture of
      actual effects. This experience has regulatory implications for HDL-raising
      therapeutics. Future programs will likely be required to provide preapproval hard
      evidence of effects on the natural history of disease.

PMID- 18047847
TI  - Liver X receptor and farnesoid X receptor as therapeutic targets.
AB  - Despite the success of existing therapies, new therapies targeted toward
      dyslipidemia are still needed. Liver X receptor (LXR) and farnesoid X receptor
      (FXR) represent 2 very different attractive targets for new therapeutic
      development. LXR is a nuclear receptor that primarily acts to rid cells and the
      body of excess cholesterol. LXR agonists have been shown to reduce
      atherosclerosis in animals and are therefore of great interest as a therapeutic
      approach. Despite some increases in hepatic fat and low-density lipoprotein (LDL)
      cholesterol in preclinical models, LXR remains an important new target. FXR is a
      nuclear receptor that primarily acts to protect hepatocytes against the effects
      of elevated bile acids. FXR agonists also have triglyceride-lowering properties
      and could be useful in treating certain types of dyslipidemia. FXR modulators or
      antagonists could potentially lower LDL cholesterol levels and even modulate high
      density lipoprotein metabolism. FXR is a complicated but fascinating target for
      the development of new therapeutic approaches.

PMID- 18047848
TI  - Lipids, lipoproteins, and peroxisome proliferator activated receptor-delta.
AB  - Peroxisome proliferator activated receptors (PPARs) are nuclear receptors
      activated by small, lipophilic compounds. Typically resident on nuclear DNA, full
      activation requires heterodimer formation with retinoid X receptor and ligand
      binding, leading to modulation in the expression of hundreds of genes. Of the 3
      described forms, (PPAR-alpha, PPAR-gamma, and PPAR-delta), PPAR-delta has been
      the least investigated. Preclinical in vitro data show that activation of PPAR
      delta, like PPAR-alpha, results in enhancement of fatty acid oxidation, leading
      to increased energy production in the form of adenosine triphosphate and of
      energy uncoupling. Microarray data in preclinical models suggest substantial PPAR
      delta expression in skeletal muscle. Exercise, which induces upregulation of PPAR
      delta in muscle tissue, leads to an increased requirement for an external or
      serum derived triacylglycerol energy source. This suggests that upregulation of
      skeletal muscle PPAR-delta would influence lipoprotein composition, this being
      the major source of combustible substrate. In the first human study using a PPAR
      delta agonist, experimental data obtained with GW 501516 (a highly specific PPAR
      delta agonist) suggested that upregulated enzymes critical to fatty acid
      oxidation in human cells enhanced fatty acid and beta-oxidation in skeletal
      muscle.

PMID- 18047849
TI  - Increasing high-density lipoprotein cholesterol, inhibition of cholesteryl ester
      transfer protein, and heart disease risk reduction.
AB  - Our purpose is to review recent research in the area of high-density lipoprotein
      (HDL) cholesterol raising and coronary artery disease (CAD) risk reduction. It is
      known that a decreased HDL cholesterol level is an important CAD risk factor and
      that raising HDL cholesterol has been associated with CAD risk reduction. A
      relative new strategy for raising HDL cholesterol, inhibition of cholesteryl
      ester transfer protein (CETP), is markedly effective. CETP inhibitors prevent the
      transfer of cholesteryl ester from HDL to triglyceride-rich lipoproteins in
      exchange for triglyceride. One inhibitor, torcetrapib, binds to CETP on HDL,
      markedly increases HDL cholesteryl ester, has no effect on fecal cholesterol
      excretion, but can raise blood pressure. A large clinical trial in patients with
      CAD who were taking atorvastatin was recently stopped prematurely because of
      excess mortality in those receiving torcetrapib versus placebo, and 2 other
      trials reported no benefit of torcetrapib on coronary atherosclerosis or carotid
      intima-media thickness as compared with subjects on atorvastatin alone. The
      adverse effects of torcetrapib may be compound specific, and because the crystal
      structure of CETP is now known, it should be possible to develop more optimal
      CETP inhibitors that do not form a nonproductive complex with CETP on the HDL
      particle, as has been reported for torcetrapib. Another alternative for
      increasing HDL levels is to develop more effective and better tolerated niacin
      preparations.

PMID- 18047850
TI  - Targeting the anti-inflammatory effects of high-density lipoprotein.
AB  - The effects of systemic inflammation can impair the anti-inflammatory functions
      of high-density lipoprotein (HDL) particles. In patients with atherosclerosis
      and/or inflammatory conditions, HDLs can be modified such that they paradoxically
      increase the recruitment and activation of macrophages, upregulate the expression
      of endothelial cell adhesion molecules, and participate in the oxidation of low
      density lipoproteins (LDLs). Statins, apolipoprotein A-I mimetic peptides, and
      therapeutic lifestyle changes appear to mitigate these proinflammatory features
      of HDLs. In the future, characterizing and targeting functional aspects of HDLs
      may prove to offer therapeutic advantages over current treatment strategies.

PMID- 18047851
TI  - High-density lipoprotein metabolism: potential therapeutic targets.
AB  - It is well recognized that the lowering of low-density lipoprotein (LDL)
      cholesterol can substantially reduce coronary artery disease (CAD)-related
      morbidity and mortality. The prevention and management of CAD has chiefly focused
      on 1 component of the lipid profile: the reduction of LDL cholesterol. Yet, the
      majority of patients in both the primary and secondary prevention settings
      continue to experience significant residual risk for acute cardiovascular events
      even when their LDL cholesterol is lowered aggressively with combinations of
      lifestyle modification and pharmacologic intervention. As a result, there is
      increased focus on targeting and treating low serum levels of high-density
      lipoprotein (HDL) cholesterol in an effort to further reduce risk for
      cardiovascular events, including myocardial infarction, unstable angina, ischemic
      stroke, and death. Epidemiologically high serum levels of HDL cholesterol are
      associated with reduced risk for the development of atherosclerotic disease. HDL
      particles are believed to be antiatherogenic secondary to their capacity to drive
      reverse cholesterol transport and antagonize pathways of inflammation,
      thrombosis, and oxidation. HDL cholesterol can be quite challenging to raise in
      many individuals because of the large number of polymorphisms in the genes,
      enzymes, cell surface receptors, and apoproteins that regulate the serum
      concentrations, functionality, and patterns of metabolism of HDL particles This
      article reviews HDL metabolism and established as well as emerging therapeutic
      approaches to raising serum concentrations of this fascinating and complex
      lipoprotein.

PMID- 18047852
TI  - Novel peroxisome proliferator activated receptor-alpha agonists.
AB  - Peroxisome proliferator activated receptors (PPARs) regulate expression of key
      genes controlling lipid and glucose metabolism through their role as ligand
      activated transcription factors. As PPARs play major roles in the regulation of
      lipid metabolism, glucose homeostasis, and inflammatory processes, they are ideal
      targets for therapeutic management strategies for cardiovascular disease. This
      article discusses the role of PPARs in the treatment of cardiometabolic
      abnormalities involved in cardiovascular risk.

PMID- 18047853
TI  - Refocusing on use of cholesteryl ester transfer protein inhibitors.
AB  - Cholesteryl ester transfer protein (CETP) plays an important role in cholesterol
      metabolism because it is responsible for the transfer of cholesteryl esters from
      high-density lipoprotein (HDL) to very-low-density lipoproteins and low-density
      lipoproteins (LDLs). The development of CETP inhibitors represented a novel
      approach for raising HDL cholesterol and reducing LDL cholesterol levels to alter
      atherogenesis. However, results from recent clinical trials question the
      therapeutic use of at least 1 CETP inhibitor, torcetrapib (Pfizer Inc, New York,
      NY), which was demonstrated to increase blood pressure and have no effect on
      decreasing the progression of coronary atherosclerosis. This article discusses
      the use of CETP inhibitors and their effects on lipoprotein metabolism and
      whether they can ultimately lead to reductions in cardiovascular events.

PMID- 18047854
TI  - Nicotinic acid (niacin) receptor agonists: will they be useful therapeutic
      agents?
AB  - Nicotinic acid (niacin) favorably affects very-low-density lipoprotein (VLDL),
      low-density lipoprotein (LDL), and lipoprotein (a) (LP[a]) and increases high
      density lipoprotein (HDL). Emerging data indicates vascular anti-inflammatory
      properties to additionally account for niacin's proven effects in cardiovascular
      disease. Recent evidence indicates that niacin acts on GPR109A and GPR109B (HM74A
      and HM74, respectively), receptors expressed in adipocytes and immune cells. In
      adipocytes, GPR109A activation reduces triglyceride (TG) lipolysis, resulting in
      decreased free fatty acid (FFA) mobilization to the liver. In humans, this
      mechanism has yet to be confirmed because the plasma FFA decrease is transient
      and is followed by a rebound increase in FFA levels. New evidence indicates
      niacin directly inhibits diacylglycerol acyltransferase 2 (DGAT2) isolated from
      human hepatocytes, resulting in accelerated hepatic apolipoprotein (apo)B
      degradation and decreased apoB secretion, thus explaining reductions in VLDL and
      LDL. This raises important questions as to whether stimulation of GPR109A in
      adipocytes or inhibition of DGAT2 in liver by niacin best explain the reduction
      in VLDL and LDL in dyslipidemic patients. Kinetic and in vitro studies indicate
      that niacin retards the hepatic catabolism of apoA-I but not liver scavenger
      receptor B1-mediated cholesterol esters, suggesting that niacin inhibits hepatic
      holoparticle HDL removal. Indeed, recent preliminary evidence suggests that
      niacin decreases surface expression of hepatic beta-chain of adenosine
      triphosphate synthase, which has been implicated in apoA-I/HDL holoparticle
      catabolism. GPR109A-mediated production of prostaglandin D2 in macrophages and
      Langerhan cells causes skin capillary vasodilation and explains, in part,
      niacin's effect on flushing. Development of niacin receptor agonists would,
      theoretically, result in adipocyte TG accumulation (and clinical adiposity) and
      increased flushing. This raises questions about niacin receptor agonists as
      therapeutic agents. Several niacin receptor agonists have been developed and
      patented, but their clinical effects have not been described. Future research is
      needed to determine whether niacin receptor agonists will demonstrate all the
      beneficial properties of nicotinic acid on atherosclerosis and without
      significant adverse effects.

PMID- 18047855
TI  - High-density lipoprotein mimetics: focus on synthetic high-density lipoprotein.
AB  - Epidemiologic studies show an inverse relation between high-density lipoprotein
      (HDL) cholesterol levels and coronary artery disease, and proof-of-concept
      experimental studies suggest that HDL and its apolipoproteins, specifically
      apolipoprotein (apo) A-I , have atheroprotective effects. Atheroprotective
      effects of HDL are attributed to its ability to remove macrophage cholesterol by
      stimulating reverse cholesterol transport as well as anti-inflammatory and
      antioxidant effects. Several different strategies are currently being pursued to
      exploit the vascular-protective effects of HDL. One such approach involves direct
      administration of synthetic reconstituted HDL made from linking phospholipid
      carriers with recombinant mutant apoA-I or plasma-derived wild-type apoA-I.

PMID- 18047856
TI  - [Headaches, facial pain, cervical pain and ear aches].

PMID- 18047857
TI  - [Pain as a symptom in otolaryngology conditions].
AB  - Pain is very frequent in otolaryngology disease: headaches, facial pain,
      earaches, and neck pain. The search for nasal pathology with maxillary sinus,
      sphenoidal, or ethmoidal involvement is part of the workup for headache. Facial
      pain should first suggest symptomatic neuralgia through involvement of the
      cranial nerves - trigeminal, glossopharyngeal, superior laryngeal - even if
      asymptomatic neuralgia are the most frequent. Earaches should be investigated
      through a search for involvement of the ear at the pinna, the external acoustic
      conduit, and the tympanic membrane. If the ear examination is normal, pain
      irradiating from the masticatory apparatus, the parotid, or the oropharynx is
      undertaken, with a systematic search for a tumoral cause.

PMID- 18047858
TI  - [Pain asssessment methods in otolaryngology].
AB  - Evaluation of pain in otolaryngology diseases is indispensable in treating
      patients. Parallel to the etiological diagnosis of otolaryngology disease, a
      clinical diagnosis of the pain must be made to determine the weighting of the
      three causes of pain involved in any acute or chronic condition: the component of
      nociceptive, neurogenic, and psychofunctional pain. This paper will discuss how
      pain can be quantified and qualified, and how to identify the status of the
      neurological system of perception and control of the pain process.

PMID- 18047859
TI  - [Nociception and chronic oral and cervicofacial pain].
AB  - This short review focuses on the main properties of the nervous system
      responsible for pain originating from oral, nasal and pharyngeal cavities. First,
      the major roles of the somatic sensations coming from the orofacial and
      pharyngeal areas are emphasized. Then, the description of the respective
      peripheral fields of the different cranial nerves involved in these somatic
      sensations is followed by the description of the primary afferent neurons and the
      central nuclei and pathways. The review emphasizes that pain does not result from
      a simple transmission of nervous impulses that would follow a fixed "hardwire"
      pathway but, on the contrary, results from an ever-changing balance between
      excitatory and inhibitory influences. These descending influences and other
      mechanisms may lead acute pain to become chronic through plastic changes of the
      nervous system and possible neuropathic changes. Finally, certain psychosocial
      factors that may facilitate chronic pain arousal are discussed.

PMID- 18047860
TI  - [Prevention and relief of pain induced by otolaryngology procedures].
AB  - There are many types of pain induced in otolaryngology, stemming from medical
      acts, sinus drainage, packing of the nasal fossae, or complex bandaging after
      cancer surgery. In patients with impaired communication abilities resulting from
      impaired speech, greater attention must be paid to induced pain, sometimes
      requiring the use of behavioral evaluation scales. Preventing this pain means
      organizing medical acts and painful treatments by attempting to group them and
      informing the patient that the caregiver is listening to him and relieving his
      pain. Non-drug treatments should always be attempted, are based on a trusting
      relationship with the patient, a comfortable position, diverting his attention,
      and using bandaging that is less painful when removed. However, use of drug
      treatments often remains indispensable. The strong morphinics are used most often
      despite a pharmacokinetic profile that is poorly adapted and the undesirable side
      effects in case of repeated administration. Local anesthetics should be used
      whenever possible. Dissemination of nursing protocols for the use of MEOPA
      provides good pain relief providing that there are trained personnel in
      sufficient numbers. The intensity of pain induced by certain medical acts
      requires use of brief general anesthesia, which can often be done in the
      ambulatory situation and is preferable to deep sedation outside of the safety of
      the operating room.

PMID- 18047861
TI  - [Prevention and relief of pain induced by otolaryngological and cervicofacial
      surgery].
AB  - Pain after otolaryngological and cervicofacial surgery varies greatly because of
      the wide variety of procedures. Preventing this pain stems from the
      administration of paracetamol, nonsteroid anti-inflammatory drugs, nefopam, and
      systematic recourse to morphine when remifentanil is used. Postoperatively, the
      most painful surgical procedures are an indication for multimodal anesthesia and
      patient-controlled morphinic analgesic after titration in the postoperative
      postanesthesia care unit. Applying antalgic protocols, also including
      locoregional anesthesia, depending on the type of procedure and the patient, can
      improve the quality of care.

PMID- 18047862
TI  - [Pain related to head and neck cancers during disease progression].
AB  - Head and neck cancers can be revealed by pain symptoms caused by an excess of
      nociception. Other pain sometimes occurs during the cancer's progression such as
      neuropathic or mixed pain. These should incite the clinician to be watchful so as
      not to miss recurrence of the cancer. Treatment is complex, requiring management
      by a multidisciplinary team.

PMID- 18047863
TI  - [Otolaryngological cancer pain at the after-effects stage].
AB  - The standards of pharyngolaryngeal tumor treatment have changed over the years in
      an attempt to prevent laryngeal mutilation (partial surgery, endoscopic surgery,
      sequential radiotherapy, and chemotherapy). Pain induced by these treatments is
      frequent and varies from one treatment to another. Chemoradiotherapy induces less
      pain but often more severe pain, since 20% of these situations are not controlled
      by strong opioids. Pain from mucositis, although nonspecific to otolaryngic
      cancer, is more frequent and more severe, and prevention and treatment remain
      poorly defined. Pain from postradiotherapeutic necrosis (mandibula, laryngeal
      cartilage, etc.) is less frequent, delayed, and extremely severe. Cervical and
      shoulder pain is present in more than one-third of patients and stems from a
      number of mechanisms (myofascial and articulatory). It is secondary to
      radiotherapy or surgery (XIth cranial nerve lesions during curage or flap
      reconstruction). Finally, pain coexists with disturbances of basic functions
      (speech, swallowing, etc.) and the disability generated by treatments. Management
      of pain, suffering, and the psychosocial impact is essential.

PMID- 18047864
TI  - [Headaches and migraines].
AB  - A 2004 update of the International Headache Society classification refined the
      diagnostic criteria for headaches, the most frequent of which remain tension
      headaches and migraines. Diagnosis remains essentially clinical, while
      complementary neuroimaging tests are done on an on-request basis for newly
      appearing headaches or for changes in migraine episodes. Given the topographies
      of migraines and tension headaches, when their characteristics are atypical, the
      otolaryngological hypothesis is often suggested. If in doubt, a test treatment
      with triptans can be attempted.

PMID- 18047865
TI  - [Cluster headache and other trigeminal-autonomic headaches].
AB  - Cluster headache is a primary headache with a male predominance that presents in
      two forms: episodic and chronic, occurring at 45-to 60-day intervals with one to
      three headaches a day lasting 45 min to 2 h. An attack starts by a violent
      unilateral retro-ocular pain with sympathetic signs such as tearing and
      rhinorrhea. Diagnosis is made by questioning and therefore requires no
      complementary tests. Treatment for the attack consists of injectable sumatriptan
      or oxygen therapy, with long-term treatment with verapamil, lithium salts, or
      Topiramate; in certain cases in which the number of attacks is greater than two,
      injections of corticosteroids at the emergence of the Arnold nerve can be used,
      or in cases of attacks resistant to all treatments, hypothalamus stimulation
      surgery can be useful.

PMID- 18047866
TI  - [Primary and secondary stomatodynia: a difficult diagnosis].
AB  - Primary stomatodynia involves mainly women after menopause presenting
      somatization, depression and anxiety at values higher than control subjects. This
      chronic pain is often an intense burning pain beginning in the tongue the entire
      oral cavity, increasing in intensity through the day with a high level of
      emotional after effects. These patients often describe two associated symptoms:
      mouth dryness sensation and altered taste. The causes remain uncertain. The
      participation of female sexual hormones and neuropathic factors has been
      suggested possibly through a sensory neuropathy of small fibers of the oral
      mucosa. Normal clinical examinations and non clinical tests differentiate primary
      from secondary stomatodynia. The management consists in using low doses of
      topical clonazepam without swallowing or systemic clonazepam. The association of
      this drug with tricyclic antidepressants has given variable results. A cognitive
      behavioural management has been successfully attempted.

PMID- 18047867
TI  - [Pain and functional problems with the temporomandibular joint].
AB  - Pain and functional problems with the temporomandibular joint present a variety
      of clinical forms. Contrary to what has been described for many years, they do
      not correspond to a syndrome. Questioning the patient and clinical examination
      are most often sufficient to specify the type of dysfunction of the manducatory
      apparatus. Treatment, which will not be detailed in this article, is oriented
      toward reversible treatments such as occlusal appliances, rehabilitation, or
      maxillofacial physical therapy.

PMID- 18047868
TI  - [Pain associated with craniofacial and cervical herpes zoster].
AB  - Ophthalmological and cervical involvement of herpes zoster virus ranks second and
      third, respectively, in terms of localization frequency. Involvement of the
      cranial nerves is a particular sign of complications, notably ocular
      complications, possibly compromising the visual or facial prognosis through
      involvement of the VIIth nerve, which is responsible for facial paralysis. These
      types of involvement should be rapidly diagnosed and treated so as to limit these
      complications. The pain associated with herpes zoster remains frequent and
      difficult to treat, even if today the criteria for defining postzoster pain is
      increasingly refined. Antalgic and antiviral treatment should be initiated early,
      from the very first signs, to attempt to reduce the incidence of this postzoster
      pain. The risk factors, associated with the development of postzoster pain are
      age over 50 years, the severity of the skin rash and the intensity of the acute
      pain, and the existence of a prodromic pain phase before onset. The European
      Federation of Neurological Societies has recently published guidelines on the
      pharmacological treatments for postzoster pain. Nerve block treatments remain at
      a limited evidence level. Patients with postzoster pain should be managed by
      teams specializing in pain management as soon as conventional treatments fail.

PMID- 18047869
TI  - Comparison of the effectiveness of amitriptyline and gabapentin on chronic
      neuropathic pain in persons with spinal cord injury.
AB  - OBJECTIVE: To test the hypotheses that both amitriptyline and gabapentin are more
      effective in relieving neuropathic pain than an active placebo, diphenhydramine.
      DESIGN: Randomized, controlled, double blind, triple crossover 8-week trial.
      SETTING: Veterans Affairs medical center. PARTICIPANTS: Community dwelling adults
      with spinal cord injury (N=38) were recruited by telephone, letters, and flyers.
      INTERVENTION: Eight-week trial each of amitriptyline, gabapentin, and
      diphenhydramine. MAIN OUTCOME MEASURES: Pain intensity measured with a 10-cm
      visual analog scale (VAS) and an 11-point (0-10) numeric rating scale (NRS) and
      depressive symptomatology measured with the Center for Epidemiologic Studies
      Depression Scale-Short Form (CESD-SF). RESULTS: Baseline VAS scores for
      participants with low (< 10) CESD-SF scores was 4.61 and for those with high
      scores (> or = 10) it was 7.41. At week 8, in participants with high baseline
      CESD-SF scores, amitriptyline (mean, 4.21) was more effective than
      diphenhydramine (mean, 6.67; P=.035), and there was a nonsignificant trend
      suggesting that amitriptyline may be more effective than gabapentin (mean, 6.68;
      P=.061). Gabapentin was no more effective than diphenhydramine (P=.97). There was
      no significant difference among the medications for those with lower CESD-SF
      scores. Results could not be attributed to dropout rates, order or dose of
      medications, amount of medication taken for breakthrough pain, or side effects.
      CONCLUSIONS: Amitriptyline is more efficacious in relieving neuropathic pain than
      diphenhydramine at or below the level of spinal cord injury in people who have
      considerable depressive symptomatology.

PMID- 18047870
TI  - Treatment efficacy of social communication skills training after traumatic brain
      injury: a randomized treatment and deferred treatment controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of a replicable group treatment program to
      improve social communication skills after traumatic brain injury (TBI). DESIGN:
      Randomized treatment and deferred treatment controlled trial, with follow-up at
      3, 6, and 9 months post-treatment. SETTING: Community. PARTICIPANTS: Volunteer
      sample of 52 people with TBI who were at least 1 year postinjury, who received
      rehabilitation, and who had identified social communication deficits.
      INTERVENTION: Twelve weekly group sessions (1.5 h each) to improve social
      communication. MAIN OUTCOME MEASURES: The Profile of Functional Impairment in
      Communication (PFIC), Social Communication Skills Questionnaire-Adapted (SCSQ-A),
      Goal Attainment Scale (GAS), Craig Handicap Assessment and Reporting Technique
      Short Form social integration and occupation subscales, Community Integration
      Questionnaire social integration and productivity subscales, and Satisfaction
      With Life Scale (SWLS). RESULTS: Independent samples t test analysis showed
      significant treatment effect compared with no treatment on 7 of 10 of the PFIC
      subscales (P range, .024 to <.001) and the SCSQ-A (P=.005) after the first 12
      weeks of the study. After 12 weeks of treatment for all participants, repeated
      measures analysis showed significant improvements from baseline on 9 of 10 PFIC
      subscales (P range, .01-.001), SCSQ-A (P < or = .001), GAS (P < or = .001), and
      SWLS (P = .011). At 6-month follow-up, scores were significantly better than
      baseline on 6 of 10 PFIC scales (P range, .01-.001), the SCSQ-A (P < or = .001),
      GAS (P < or = .001), and SWLS (P < or = .001). CONCLUSIONS: TBI subjects who
      received social communication skills training had improved communication skills
      that were maintained on follow-up. Overall life satisfaction for participants was
      improved.

PMID- 18047871
TI  - The effect of a series of repetitive transcranial magnetic stimulations of the
      motor cortex on central pain after spinal cord injury.
AB  - OBJECTIVE: To study the analgesic effect of repetitive transcranial magnetic
      stimulation (rTMS) of the motor cortex on central pain in patients with chronic
      spinal cord injury (SCI). DESIGN: Double-blind randomized controlled trial. Mean
      follow-up period was 4.5 weeks. SETTING: General hospital. PARTICIPANTS: Twelve
      paraplegic patients due to thoracic SCI suffering chronic central pain (11
      completed the study) who were randomly selected from a list of eligible patients.
      INTERVENTION: Real or sham 10 daily motor rTMS treatments (500 trains at 5 Hz for
      10 s; total of 500 pulses at intensity of 115% of motor threshold) using figure
      of-8 coil over the vertex. MAIN OUTCOME MEASURES: Chronic pain intensity (visual
      analog scale [VAS], McGill Pain Questionnaire [MPQ]), pain threshold, and level
      of depression (Beck Depression Inventory). RESULTS: Both real and sham TMS
      induced a similar, significant reduction in VAS scores (P<.001) immediately after
      each of the 10 treatment sessions and in VAS and MPQ scores after the end of the
      treatment series. However, only real rTMS conferred a significant increase in
      heat-pain threshold (4 degrees C, P<.05) by the end of the series. Most
      important, the reduction in MPQ scores in the real rTMS group continued during
      the follow-up period. Depression scores were equally reduced in both groups but
      similar to pain relief, depression continued to improve at follow-up in the real
      rTMS group. CONCLUSIONS: Whereas the pain alleviation induced by a single rTMS
      treatment is probably due to placebo, patients with SCI may benefit from a series
      of rTMS treatments.

PMID- 18047872
TI  - Efficacy of cognitive-behavioral therapy for insomnia associated with traumatic
      brain injury: a single-case experimental design.
AB  - OBJECTIVE: To test the efficacy of a cognitive-behavioral therapy (CBT) for
      insomnia in persons having sustained traumatic brain injury (TBI). DESIGN: Single
      case design with multiple baselines across participants. SETTING: Outpatient
      rehabilitation center. PARTICIPANTS: Eleven subjects having sustained mild to
      severe TBI who developed insomnia after the injury. INTERVENTION: Eight-week CBT
      for insomnia including stimulus control, sleep restriction, cognitive
      restructuring, sleep hygiene education, and fatigue management. MAIN OUTCOME
      MEASURES: Total wake time, sleep efficiency, and diagnostic criteria. RESULTS:
      Visual analyses, corroborated by intervention time series analyses and t tests,
      revealed clinically and statistically significant reductions in total wake time
      and sleep efficiency for 8 (73%) of 11 participants. An average reduction of
      53.9% in total wake time was observed across participants from pre- to post
      treatment. Progress was in general well maintained at the 1-month and 3-month
      follow-ups. The average sleep efficiency augmented significantly from
      pretreatment (77.2%) to post-treatment (87.9%), and also by the 3-month follow-up
      (90.9%). Improvements in sleep were accompanied by a reduction in symptoms of
      general and physical fatigue. CONCLUSIONS: The results of this study show that
      psychologic interventions for insomnia are a promising therapeutic avenue for TBI
      survivors.

PMID- 18047873
TI  - The immediate effect of attentional, auditory, and a combined cue strategy on
      gait during single and dual tasks in Parkinson's disease.
AB  - OBJECTIVE: To compare the effect of rhythmic auditory and attentional cues, and a
      combination of both cues on gait, in people with Parkinson's disease (PD) during
      single and dual tasks. DESIGN: A repeated-measures study requiring participants
      to perform single and dual-motor tasks under different cueing conditions.
      SETTING: Human movement analysis laboratory. PARTICIPANTS: Fifteen participants
      with idiopathic PD and a comparison group of 12 healthy participants.
      INTERVENTIONS: Three cueing strategies were compared: a rhythmic auditory cue
      (walking in time to a metronome beat), an attentional strategy (asked to focus on
      taking big step), and a combination cue (asked to walk in time to a metronome
      beat while taking big steps). MAIN OUTCOME MEASURES: Walking speed, step
      amplitude, and step frequency. RESULTS: Walking speed of PD participants improved
      significantly compared with noncued walking in the single- and dual-task
      condition with the attentional (P<.001, P=.037) and combination cue strategies
      (P=.013, P=.028). Step amplitude also increased significantly with the
      attentional and combination cue strategies in single- (P<.001, P<.001) and dual
      task (P<.001, P<.001) conditions. Step frequency was reduced significantly with
      the attentional strategy (P=.042) in the single and dual tasks (P<.001) and
      combination cue strategy (P=.009) in the dual task. The rhythmic auditory cue
      alone did not alter significantly any parameter of gait in the single or dual
      tasks. CONCLUSIONS: The attentional strategy and the combination of a rhythmic
      auditory cue with an attentional strategy were equally effective, and improved
      walking speed and step amplitude significantly during both single and dual tasks.
      The combination cue, however, may still be a useful alternative in situations of
      increased attentional demand, or where problems exist with executive function.

PMID- 18047874
TI  - Clinical analysis of risk factors for falls in home-living stroke patients using
      functional evaluation tools.
AB  - OBJECTIVES: To identify risk factors associated with falls in home-living stroke
      patients and to predict falls using patient information and functional evaluation
      tools. DESIGN: Cohort study. SETTING: Community. PARTICIPANTS: We recruited 101
      home-living stroke patients who had hemiparesis and could walk independently with
      or without supporting devices. Disease duration ranged from 1 to 22 years (mean,
      6.1 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The score of each
      item of the Stroke Impairment Assessment Set (SIAS), and the FIM instrument, sex,
      age, duration of disease, stroke type, affected side of the body, frequency of
      rehabilitation, use of sedatives, and Mini-Mental State Examination score were
      evaluated and the occurrence of falls was observed prospectively for 12 months.
      RESULTS: Forty-five (44.6%) participants fell, 20 of whom fell repeatedly. A
      logistic model for predicting falls was refined until it included 4 predictors:
      memory score on the FIM, range of motion of the lower extremities on the SIAS,
      duration of disease, and affected side. The predictive value of the logistic
      model was 86.7%. CONCLUSIONS: Evaluation tools were useful for predicting falls
      and devising preventive strategies in the high-risk group of home-living stroke
      patients.

PMID- 18047875
TI  - Comparison of soleus H-reflex modulation after incomplete spinal cord injury in 2
      walking environments: treadmill with body weight support and overground.
AB  - OBJECTIVE: To investigate a walking environment effect on soleus H-reflex
      modulation during walking in persons with motor incomplete spinal cord injury
      (SCI) and noninjured controls. DESIGN: Pretest and posttest repeated-measures
      quasi-experimental controlled design. SETTING: Locomotor training laboratory.
      PARTICIPANTS: Eight adults with incomplete SCI and 8 noninjured age- and speed
      matched controls. INTERVENTION: Walking overground with a customary assistive
      device and brace at a self-selected, comfortable walking speed was compared with
      walking on treadmill with 40% body weight support (BWS) and manual trainers for
      leg and trunk movement guidance. MAIN OUTCOME MEASURE: Mean soleus H-reflex
      amplitude (H/M ratio) was recorded during midstance and midswing phases of
      walking. RESULTS: The H/M ratio was 33% smaller in stance phase (P=.078) and 56%
      smaller in the swing phase (P=.008) of walking on the treadmill with BWS and
      manual assistance compared with overground in the incomplete SCI group. The H/M
      ratio in the incomplete SCI group was significantly greater compared with
      noninjured controls in the stance and swing phases of overground walking (P=.001,
      P=.007, respectively). Soleus H-reflex modulation in the 2 walking environments
      did not differ significantly in the noninjured population. CONCLUSIONS: Training
      walking on a treadmill with BWS and manual assistance to approximate the
      kinematics and spatiotemporal pattern of walking may be a more optimal
      environment to aid in normalizing reflex modulation after incomplete SCI when
      compared with conventional gait training overground.

PMID- 18047876
TI  - Development and validation of the balance outcome measure for elder
      rehabilitation.
AB  - OBJECTIVE: To develop and investigate the internal consistency, criterion-related
      validation, and minimum clinically significant difference of a new standing
      balance outcome measure for Elder Rehabilitation. DESIGN: Three phases: (1) cross
      sectional survey with expert panel, (2) multicenter prospective cohort randomly
      divided into development and validation datasets, and (3) prospective cohort
      (single site). SETTING: Geriatric and rehabilitation units across 2 states in
      Australia. PARTICIPANTS: A total of 1769 admissions across 17 geriatric
      assessment and rehabilitation units. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: The Balance Outcome Measure for Elder Rehabilitation (BOOMER) consisted
      of the step test, Timed Up & Go test, Functional Reach Test, and static standing
      with feet together and eyes closed test. Criterion-related validity was
      established through comparison to the Modified Elderly Mobility Scale (MEMS) and
      the FIM motor score. RESULTS: Items of the BOOMER were already used at a majority
      of rehabilitation facilities surveyed. The BOOMER showed high levels of internal
      consistency (Cronbach alpha>.87) and had good correlation with the FIM motor and
      the MEMS (rho>.72). The minimum clinically significant change in the BOOMER was 3
      points over a 17-point scale range. CONCLUSIONS: The BOOMER is a clinically
      applicable measure of standing balance among older rehabilitation patients with
      evidence of content and construct validity.

PMID- 18047877
TI  - Effect of 2-speed geared manual wheelchair propulsion on shoulder pain and
      function.
AB  - OBJECTIVE: To investigate the impact of a manual 2-gear drive wheelchair wheel
      (MAGICWheels) on shoulder pain and function in manual wheelchair users. DESIGN: A
      single-group, repeated-measures pre- and postdesign with baseline and retention.
      SETTING: General community. PARTICIPANTS: Full-time manual wheelchair users
      (N=17) currently experiencing shoulder pain (mean age, 46+/-14 y; wheelchair use,
      15+/-10 y). INTERVENTION: Five-month trial using a 2-gear wheelchair wheel. MAIN
      OUTCOMES MEASURES: The Wheelchair Users Shoulder Pain Index (WUSPI), Wheelchair
      Users Functional Assessment (WUFA), and timed hill climb test with rating of
      perceived exertion (RPE). RESULTS: There was significant reduction in shoulder
      pain after the intervention at week 2 (P=.004) through week 16 (P=.015). The
      difference was not found at week 20; however, 1 participant reported an increase
      in pain from unrelated factors during week 20. Change from baseline was
      calculated without this subject's data; there was a significant reduction in
      shoulder pain (P=.003). There was no difference in WUFA after using the 2-gear
      wheel (P=.06). Hill climb time was longer when using the 2-gear wheel (P=.01),
      but no difference in the RPE (P=.13) resulted. Shoulder pain during the 4-week
      retention phase showed a trend toward increasing, as indicated by increased WUSPI
      scores. There was not a significant percentage increase, however, in comparison
      with the final week of using the MAGICWheels (P<.05). CONCLUSIONS: There were
      pain reductions 2 weeks after using the MAGICWheels, indicating a rapid response
      to the intervention. These findings indicate the potential for shoulder pain
      reduction with the use of a manual drive wheel during mobility, even in highly
      functional manual wheelchair users.

PMID- 18047878
TI  - Psychosocial subgroups in persons with spinal cord injuries and chronic pain.
AB  - OBJECTIVES: To define adaptational subgroups in people with chronic pain and
      spinal cord injury (SCI), and to compare these subgroups with respect to
      demographic factors, level of injury, functional independence, pain disability,
      depressed mood, social support, and life satisfaction. DESIGN: Interviews.
      SETTING: Veterans Affairs medical center and The Miami Project to Cure Paralysis.
      PARTICIPANTS: Persons with SCI and chronic pain (N=190). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: The Multidimensional Pain Inventory, SCI
      version. RESULTS: Cluster analysis revealed 3 subgroups: (1) dysfunctional (34.6%
      of all participants), characterized by higher pain severity, life interference,
      and affective distress scores, and lower levels of life control and activities
      scores; (2) interpersonally supported (33.0% of participants), characterized by
      moderately high pain severity, and higher life control, support from significant
      others, distracting responses, solicitous responses, and activities scores; and
      (3) adaptive copers (32.4% of participants), characterized by lower pain
      severity, life interference, affective distress, support from significant others,
      distracting responses, solicitous responses, activities and higher life control
      scores. Compared with the dysfunctional subgroup, the interpersonally supported
      subgroup reported significantly greater social support and life satisfaction and
      less pain disability and emotional distress, despite moderately high pain
      severity. CONCLUSION: Three subgroups, independent of sex, pain duration, and
      functional status, were identified. Although severe pain significantly decreases
      life satisfaction after SCI, its impact is moderated by perceived social support.

PMID- 18047879
TI  - Perceived environmental barriers to recreational, community, and school
      participation for children and youth with physical disabilities.
AB  - OBJECTIVE: To comprehensively describe parent perceptions of environmental
      barriers to recreational, community, and school participation for children with
      physical disabilities. DESIGN: Secondary analysis of cross-sectional data
      gathered in the first wave of a longitudinal study of the child, family, and
      environmental factors affecting the recreational and leisure participation of
      school-age children with physical disabilities. SETTING: General community.
      PARTICIPANTS: Parent-child pairs (N=427). Child participants included 229 boys
      and 198 girls with physical disabilities in 3 age cohorts (6-8, 9-11, 12-14 y).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Craig Hospital Inventory of
      Environmental Factors. RESULTS: Barriers to participation were encountered in
      school and work environments (1.54+/-1.88), physical and built environments
      (1.36+/-1.35), within institutional and government policies (1.24+/-1.71),
      services and assistance (1.02+/-1.2), and attitudes and social support (.87+/
      1.17). Age, socioeconomic status, level of physical functioning, and behavioral
      difficulties were related to the impact of barriers reported in certain areas. No
      significant differences by the sex of the children or rural versus urban
      community were found. CONCLUSIONS: Parents report environmental barriers in
      several areas, providing valuable information about the environmental factors
      that support or hinder participation while showing the complexity of these
      issues. Future research is required to further identify potential avenues for
      intervention.

PMID- 18047880
TI  - Relationship between quality of life and self-efficacy in persons with spinal
      cord injuries.
AB  - OBJECTIVE: To study the interaction between quality of life in people with spinal
      cord injury (SCI) and expectations of daily living (self-efficacy) and pain.
      DESIGN: Cross-sectional study with multiple independent measures. SETTING: Home
      survey. PARTICIPANTS: Included 106 persons with SCI of 12 months or more in
      duration who were living in the community and had enrolled from past admission
      lists in a rehabilitation unit. INTERVENTION: Participants received no treatments
      as part of the study but were asked to complete 2 questionnaires by postal survey
      in their postrehabilitation stage. MAIN OUTCOME MEASURES: The Medical Outcomes
      Study 36-Item Short-Form Health Survey (SF-36) and the Moorong Self-Efficacy
      Scale. RESULTS: Persons with SCI were found to have lowered quality of life (QOL)
      compared with the Australian general population. Low self-efficacy and pain
      intensity were found to reduce QOL across all SF-36 domains even further. Factors
      such as completeness of lesion, sex, age at time of injury, and time since injury
      were not associated with reduced QOL. Tetraplegia was associated with lower QOL
      in physical functioning and greater limitation due to bodily pain. A combination
      of low self-efficacy and pain intensity was associated with an increased
      reduction in QOL compared with reductions seen for these factors by themselves.
      CONCLUSIONS: Rehabilitation strategies may need to concentrate on improving QOL
      by targeting factors like low self-efficacy.

PMID- 18047881
TI  - Measures of physical functioning predict self-reported performance in self-care,
      mobility, and domestic life in ambulatory persons with multiple sclerosis.
AB  - OBJECTIVE: To determine the associations between clinically measured physical
      functioning variables and self-reported performance in mobility, self-care, and
      domestic life in ambulatory persons with multiple sclerosis (MS), using the
      International Classification of Functioning, Disability and Health (ICF) as a
      framework. DESIGN: Survey study. SETTING: Community setting in Finland.
      PARTICIPANTS: A population-based sample of 120 ambulatory persons with MS (30
      men, 90 women) with mean age 45.0+/-10.8 years (range, 20-71 y), mean disease
      duration from symptom onset 12.3+/-8.8 years (range, 1-39 y), and mean Expanded
      Disability Status Scale 2.8+/-2.0 (range, 0-6.5). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: The primary dependent variables were self-reported
      performance in self-care, mobility, and domestic life from the Functional Status
      Questionnaire. The physical functioning variables were drawn from the ICF
      activities (n=9) and body functions (n=14) categories. Age- and sex-adjusted odds
      ratios from multinomial logistic regression were estimated for the physical
      functioning variables associated with activities of daily living (ADL)
      performance. RESULTS: Overall, of this cohort 31% reported difficulties or
      dependence in self-care, 52% in mobility, and 68% in domestic life. The most
      significant predictors of perceived difficulties or dependence in ADL performance
      were: (1) lower scores in the Box and Block Test; (2) lower Berg Balance Scale
      scores; (3) greater velocity moment when standing with eyes open; (4) slower ten
      meter walk test times and shorter stride length at normal speed; and (5) shorter
      distance in the six-minute walk test. CONCLUSIONS: Perceived difficulties and
      dependence were most prominent in domestic life. In particular, measures of
      activities predicted difficulties in ADL performance. Monitoring of physical
      functioning should be extended to those independent MS persons reporting
      difficulties in ADL performance.

PMID- 18047882
TI  - Identification and quantification of myofascial taut bands with magnetic
      resonance elastography.
AB  - OBJECTIVE: To explore the feasibility of using a new magnetic resonance imaging
      (MRI) technique--magnetic resonance elastography (MRE)--to identify and
      quantitate the nature of myofascial taut bands. DESIGN: This investigation
      consisted of 3 steps. The first involved proof of concept on gel phantoms, the
      second involved numeric modeling, and the third involved a pilot trial on 2
      subjects. Imaging was performed with a 1.5 T MRI machine. Shear waves were
      produced with a custom-developed acoustically driven pneumatic transducer with
      gradient-echo image collection gated to the transducer's motion. Shear wave
      propagation were imaged by MRE. SETTING: An MRI research laboratory.
      PARTICIPANTS: Two women, one with a 3-year history of myofascial pain and the
      other serving as the control. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: MRE images, finite element analysis calculations, and tissue and
      phantom stiffness determinations. RESULTS: Results of the phantom measurements,
      finite element calculations, and study patients were all consistent with the
      concept that taut bands are detectable and quantifiable with MRE imaging. The
      findings in the subjects suggest that the stiffness of the taut bands (9.0+/-0.9
      KPa) in patients with myofascial pain may be 50% greater than that of the
      surrounding muscle tissue. CONCLUSIONS: Our findings suggest that MRE can
      quantitate asymmetries in muscle tone that could previously only be identified
      subjectively by examination.

PMID- 18047883
TI  - Assessing subclinical tactual deficits in the hand function of diabetic blind
      persons at risk for peripheral neuropathy.
AB  - OBJECTIVE: To assess subclinical impairments in tactual hand function produced by
      diabetes mellitus in late-blind adults with diabetic retinopathy. DESIGN: The
      survey compares diabetic blind with nondiabetic blind and blindfolded sighted
      controls in terms of their performance on a battery of tests that assess tactual
      hand function. SETTING: Subjects were evaluated at their rehabilitation program
      center in Madrid. PARTICIPANTS: Nine (referred) diabetic blind subjects affected
      by diabetic retinopathy versus 10 (referred) nondiabetic blind subjects versus 10
      blindfolded sighted volunteers, all right-handed and matched for age. Subjects
      were referred by the training professionals of the rehabilitation program center
      and asked to volunteer. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Cutaneous force and spatial resolution thresholds, haptic psychophysical
      functions for perceived roughness, weight, and size, and both accuracy and
      response times for haptic classification of 3-dimensional common objects.
      Measures of joint mobility, muscular strength, and motor dexterity were also
      included. RESULTS: The diabetic blind performed significantly poorer than the
      controls in terms of force sensitivity (distal and proximal finger pads, and
      palm), spatial resolution (distal finger pad only), motor dexterity, perceived
      roughness, and finally, haptic object classification response times for texture
      diagnostic objects. CONCLUSIONS: Subclinical disturbances in the tactual hand
      function of the diabetic blind subjects were only documented in perceptual and
      motor tasks for which cutaneous, as opposed to kinesthetic, information was
      particularly relevant.

PMID- 18047884
TI  - The effect of clinically relevant pressure duration on sacral skin blood flow and
      temperature in patients after acute spinal cord injury.
AB  - OBJECTIVE: To test the effect of clinically relevant duration of pressure loading
      (2 h) on sacral skin blood flow (SBF) and skin temperature in subjects with
      spinal cord injury (SCI) within 24 to 96 hours after injury compared with
      subjects with acute orthopedic trauma and healthy subjects. DESIGN: Three-group,
      repeated-measures, inception cohort. SETTING: Three acute care hospitals in
      southern Thailand. PARTICIPANTS: Convenience sample of 20 subjects with acute SCI
      within 24 to 96 hours after injury. Age- and sex-matched subjects with acute
      orthopedic trauma (n=35) and healthy subjects (n=47) served as comparison groups.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sacral SBF and skin
      temperature were measured simultaneously by using a laser Doppler sensor and
      thermocouple sensor, respectively, with subjects lying in the lateral (baseline,
      no pressure, 30 min), supine (pressure loading, 2 h), and lateral position
      (recovery, no pressure, 90 min). RESULTS: Baseline skin temperature was higher in
      subjects with acute SCI (P<.05) compared with subjects with orthopedic trauma and
      healthy subjects. A relative decrease in sacral SBF occurred in subjects with
      acute SCI (P<.01) over 2 hours of pressure loading compared with subjects with
      orthopedic trauma and healthy subjects. During the same time course, subjects
      with acute SCI had a smaller increase in sacral skin temperature compared with
      subjects with orthopedic trauma and healthy subjects (P<.001). During recovery,
      the time to the initial sacral SBF-reactive hyperemia response was shorter in
      subjects with acute SCI compared with subjects with orthopedic trauma (P<.001)
      and healthy subjects (P=.003). Additionally, the initial positive slope of the
      SBF reactive hyperemia response was higher in subjects with acute SCI than
      subjects with orthopedic trauma (P=.005) and healthy (P=.004) subjects.
      CONCLUSIONS: Collectively, a negative change in SBF during pressure loading plus
      a shorter time to increase and greater slope for SBF after pressure release
      reveal microvascular dysfunction in acute SCI subjects. The clinical relevance of
      the protocol suggests that turning interval guidelines may require reevaluation
      for patients with acute SCI.

PMID- 18047885
TI  - Oxygen saturation and heart rate during feeding in breast-fed infants at 1 week
      and 2 months of age.
AB  - OBJECTIVE: To gather normative data about cardiopulmonary changes during feeding
      in breast-fed infants at 1 week and 2 months of age. DESIGN: Prospective cohort
      study. SETTING: General community. PARTICIPANTS: Twenty-two term-born, breast-fed
      infants. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Oxygen saturation
      (SpO2), the percentage of oxygenized hemoglobin, and heart rate were monitored
      and recorded every 30 seconds for 5 minutes before oral feeding, during the first
      10 minutes of feeding, and the first 10 minutes immediately after feeding. The
      observations were made at 1 week and 2 months of age. RESULTS: Mean SpO2 levels
      were significantly higher in 2-month-old infants (mean, 97.57) than in 1-week-old
      infants (mean, 96.35) (P=.001). SpO2 was not affected by any of the 3 trials
      (before, during, and after feeding). Heart rate was significantly affected by
      trial. Mean heart rate during feeding (mean, 152.45) was significantly higher
      than heart rate prefeeding (mean, 146.51) (P<.001), and heart rate postfeeding
      (mean, 147.12) (P=.002). Heart rate was not affected by age. CONCLUSIONS: Little
      is known about the association between feeding and cardiopulmonary status in term
      born, breast-fed infants. This longitudinal study contributes to our knowledge
      about feeding-related cardiopulmonary changes in term-born, breast-fed infants.

PMID- 18047886
TI  - Test-retest and inter- and intrareliability of the quality of the upper-extremity
      skills test in preschool-age children with cerebral palsy.
AB  - OBJECTIVE: To investigate the test-retest, inter-, and intraobserver reliability
      of the Quality of Upper Extremity Skills Test (QUEST) in young children with
      cerebral palsy (CP). DESIGN: For test-retest reliability, a test-retest design
      was used; for the intra- and interobserver reliability, the videotaped test was
      scored on 2 occasions by 1 observer and by various observers. SETTING: Groups of
      preschool-age children in 2 general rehabilitation centers. PARTICIPANTS: Twenty
      one children with CP (12 boys, 9 girls) aged 2 to 4.5 years (mean, 39 mo).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Spearman correlation
      coefficient. RESULTS: The data indicated that test-retest reliability was strong
      (rho range, .85-.94). Intraobserver agreement (rho range, .63-.95) and agreement
      between various observers (rho range, .72-.90) were moderate to strong.
      CONCLUSIONS: Test-retest and inter- and intraobserver reliability of the QUEST in
      preschool-age children with CP is good.

PMID- 18047887
TI  - Subacromial corticosteroid injection for poststroke shoulder pain: a
      retrospective chart review.
AB  - OBJECTIVE: To assess the effectiveness of subacromial corticosteroid injections
      for the treatment of poststroke shoulder pain. DESIGN: Retrospective chart
      review. SETTING: Ambulatory setting, university-affiliated hospital.
      PARTICIPANTS: People (N=60) with stroke-associated hemiparesis and pain in the
      involved shoulder. INTERVENTIONS: Electronic medical records of stroke survivors
      with shoulder pain in the hemiparetic limb treated with a subacromial
      corticosteroid injection by a practitioner between January 1, 2005, and June 30,
      2007, were reviewed. Patients who had a documented preinjection pain score on the
      day of injection by using a 0 to 10 numeric rating scale and a postinjection pain
      score within 16 weeks of injection were included. MAIN OUTCOME MEASURES: Pre- and
      postinjection scores were compared by using the paired t test. Treatment success
      was defined as a minimum of 2-point absolute or 30% relative pain reduction.
      Linear and logistic regression analyses were used to identify predictors of pain
      reduction and treatment success, respectively. RESULTS: Patients experienced an
      absolute pain reduction of 2.6+/-3.7 (95% confidence interval, 1.7-3.6; P<.001)
      and a relative pain reduction of 32.9%+/-53.6%. Fifty-three percent experienced
      the minimum 2-point absolute pain reduction, whereas 45% experienced the minimum
      30% relative pain reduction. Linear regression analyses identified the
      preinjection pain score as a predictor of absolute pain reduction and concomitant
      outpatient occupational or physical therapy as a predictor of both absolute and
      relative pain reduction. No other factors were predictive of pain reduction or
      treatment success. CONCLUSIONS: Subacromial corticosteroid injection is
      associated with a significant reduction in poststroke shoulder pain. However,
      controlled trials are needed to show a cause-and-effect relationship and rule out
      spontaneous recovery, placebo effect, and other confounds.

PMID- 18047888
TI  - Prognostic models for physical capacity at discharge and 1 year postdischarge
      from rehabilitation in persons with spinal cord injury.
AB  - OBJECTIVE: To develop prognostic models for physical capacity at discharge and 1
      year after discharge from inpatient rehabilitation in persons with spinal cord
      injury (SCI). DESIGN: Inception cohort; data collected at start of rehabilitation
      (n=104), at discharge (n=81), and 1 year later (n=74). SETTING: Eight Dutch
      rehabilitation centers. PARTICIPANTS: Patients with SCI at initial
      rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Physical
      capacity determined by endurance capacity (peak oxygen uptake [VO2peak, in L/min]
      and power output [POpeak, in watts]) during a maximal exercise test, arm muscle
      strength, and respiratory function. Multiple regression models, either with or
      without prior outcome, evaluated subject, lifestyle, and lesion-related
      predictors. RESULTS: Only start VO2peak contributed to the prediction of
      discharge VO2peak (R2=.51). Discharge VO2peak contributed to its prediction 1
      year later (R2=.75). Start POpeak, sex, age, and level of lesion contributed to
      discharge POpeak (R2=.73). Discharge POpeak, hours of employment before injury,
      and level of lesion contributed to POpeak 1 year later (R2=.81). Models without
      prior outcome explained less variance. Education, employment, body mass index,
      not smoking, and conservative stabilization of the spine positively contributed
      to endurance capacity. Muscle strength was well predicted (R2 range, .68-.84).
      Without prior outcome, respiratory function was poorly predicted. CONCLUSIONS:
      Because prior outcome contributed to an accurate prediction, the early assessment
      of physical capacity is important in establishing prognoses. Although their
      accuracy warrants caution in their application, models could complement clinical
      expertise when informing patients about expected physical outcome and identifying
      those at risk of low physical capacity.

PMID- 18047889
TI  - Education in pulmonary rehabilitation: the patient's perspective.
AB  - OBJECTIVES: To ascertain from patients' perspectives what should be included in
      the educational component of pulmonary rehabilitation and how it should be
      delivered, and to compare those perspectives with the views of health
      professionals. DESIGN: Qualitative research method using focus groups of patients
      and health professionals. SETTING: A regional respiratory center and outpatient
      clinic. PARTICIPANTS: Purposive samples of 32 patients with chronic obstructive
      pulmonary disease (COPD) (forced expiratory volume in 1 second, 18%-67%
      predicted) divided into 6 focus groups; 8 health professionals knowledgeable
      about COPD and pulmonary rehabilitation who attended a multidisciplinary focus
      group meeting. INTERVENTIONS: Participants attended focus group meetings (2-3 h)
      guided by a series of questions and topics; results were posted to the
      participants for their verification. MAIN OUTCOME MEASURE: The educational
      content of a pulmonary rehabilitation program. RESULTS: Deficits in patients'
      knowledge, understanding, and management of their disease were identified. Six
      key educational topics resulted: disease education, management of breathlessness,
      management of an exacerbation, medication, psychosocial support, and welfare and
      benefits systems. Patients and health professionals preferred group information
      sessions provided by knowledgeable people speaking layman's language, with oral
      presentations being supplemented by written information. CONCLUSIONS: Gaining a
      greater understanding of patients' educational needs permits health professionals
      who design pulmonary rehabilitation programs to include these requirements in a
      format that is acceptable to patients. The key topics, content, and format for
      delivery of the educational component for pulmonary rehabilitation were
      identified. Future research should focus on the development of an educational
      package and assessment of its efficacy, which would facilitate equitable patient
      access to education in pulmonary rehabilitation.

PMID- 18047890
TI  - Criterion validity of the StepWatch Activity Monitor as a measure of walking
      activity in patients after stroke.
AB  - OBJECTIVES: To test the validity of the StepWatch Activity Monitor (SAM) in
      subjects with stroke against 2 criterion standards, 3-dimensional gait analysis
      (3-DGA) and footswitches in a variety of indoor and outdoor walking conditions,
      including different speeds and different terrains, and to test the accuracy of
      the SAM when worn on the paretic limb. DESIGN: Criterion standard validation
      study. SETTING: Gait laboratory and outside course. PARTICIPANTS: Twenty-five
      participants with physical disability after stroke. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The total step count measured simultaneously
      by SAM and either 3-DGA or footswitches for both paretic and nonparetic limbs.
      RESULTS: The total step count measured by the SAM and 3-DGA was highly correlated
      (nonparetic limb, r=.959; paretic limb, r=.896). The 95% limits of agreement
      (LOA) (derived from Bland-Altman analysis) between the SAM and 3-DGA were within
      +/-10 steps for SAMs worn on either the nonparetic or paretic limb. The total
      step count measured simultaneously by the SAM and footswitches was also highly
      correlated for each limb (nonparetic, r=.999; paretic, r=.963). The 95% LOA
      between the SAM and footswitches were +/-9 steps on the nonparetic limb but
      higher at +/-57 steps on the paretic limb. Further analysis showed that the
      measurement differences occurred during the outdoor component of the combined
      walk. The 95% LOA between footswitches on both limbs were not more than +/-9
      steps for walking, suggesting that the error was accounted for by the SAM on the
      paretic limb, which both over- and underread the total step count in the outdoor
      walking conditions. CONCLUSIONS: Criterion validity of the SAM to measure steps
      in both clinical and natural environments has been established when used on the
      nonparetic limb. However, more errors are apparent when the SAM is worn on the
      paretic limb while walking over a variety of outdoor terrains. Validation is
      recommended before use in patients with neurologic conditions affecting bilateral
      legs because there may be more error, particularly in outdoor activities.

PMID- 18047891
TI  - The importance of an exercise testing protocol for detecting changes of peak
      oxygen uptake in cardiac rehabilitation.
AB  - OBJECTIVE: To assess which exercise testing protocol is most sensitive for
      assessing peak oxygen uptake (VO2peak) changes as a result of cardiac
      rehabilitation. DESIGN: Prospective randomized clinical trial. SETTING:
      Outpatient cardiac rehabilitation center. PARTICIPANTS: Forty-two cardiac
      patients (33 men; mean age, 65.4+/-8.4 y). INTERVENTION: All patients were
      included into a 7-week cardiac rehabilitation program and randomized in 2
      subgroups. One group of patients was evaluated by a 1-minute stage (n=21) and
      another group by a 3-minute stage (n=21) exercise testing protocol. MAIN OUTCOME
      MEASURES: In both groups, maximal cardiopulmonary exercise tests on a bicycle
      with analysis of VO2peak, expiratory volume (VE), respiratory exchange ratio,
      heart rate, cycling resistance (W), and test duration were performed at the start
      and end of the program. RESULTS: Subgroups were closely matched, and no changes
      in beta-blocker treatment occurred during this study. As result of the
      rehabilitation program, total test duration and Wpeak improved significantly in
      both groups (P<.05). Nonetheless, VO2peak and VEpeak increased significantly in
      the 1-minute stage duration group (P<.05) but not in the 3-minute stage duration
      group (P>.05). In addition, the change of VO2peak, VEpeak, and total test
      duration was significantly greater in the 1-minute stage duration group compared
      with the 3-minute stage duration group (P<.05). CONCLUSIONS: For detecting
      changes of VO2peak as result of cardiac rehabilitation, a 1-minute stage exercise
      testing protocol is more sensitive when compared with a 3-minute stage exercise
      testing protocol.

PMID- 18047892
TI  - Mechanical alterations of rabbit Achilles' tendon after immobilization correlate
      with bone mineral density but not with magnetic resonance or ultrasound imaging.
AB  - OBJECTIVE: To assess the usefulness of magnetic resonance imaging (MRI),
      ultrasound (US) imaging, or bone mineral density (BMD) in predicting the
      mechanical properties of immobilized rabbit Achilles' tendons. DESIGN:
      Experimental study. SETTING: Basic university laboratory. ANIMALS: Twenty-eight
      rabbits. INTERVENTIONS: Twelve rabbits had 1 hindlimb casted for 4 weeks and 10
      rabbits were casted for 8 weeks. Contralateral legs and 12 normal hindlimbs
      served as controls. MAIN OUTCOME MEASURES: Achilles' tendon dimensions on MRI and
      US, T1- and T2-signal intensities on MRI, classification of abnormalities on MRI
      and US; BMD of the calcaneus with dual-energy x-ray absorptiometry. Biomechanic
      measures consisted of peak load, stiffness, and stress. Imaging variables were
      correlated with biomechanic alterations. RESULTS: Immobilized Achilles' tendons
      were weaker and showed decreased mechanical stress compared with their
      contralateral legs and controls (all P<.05). MRI and US revealed larger Achilles'
      tendons after immobilization. However, neither increased MRI nor US signal
      abnormality was found. BMD was lower in immobilized calcanei and larger in
      contralateral legs than controls. Only BMD correlated with both the decreased
      peak load (R2=.42, P<.05) and stress (R2=.54, P<.05) of immobilized Achilles'
      tendon. CONCLUSIONS: This study established weakened mechanical properties of
      immobilized Achilles' tendons. BMD of the calcaneus, but not MRI and US, was
      predictive of the mechanical alterations in immobilized Achilles' tendons. BMD
      may be a useful biomarker to monitor disease and recovery in Achilles' tendons.

PMID- 18047893
TI  - Arm crank ergometry and shoulder pain in persons with spinal cord injury.
AB  - OBJECTIVE: To determine whether a primary fitness program utilizing arm crank
      ergometry would cause increased shoulder pain in persons with spinal cord injury
      (SCI). DESIGN: Cohort study. SETTING: Clinical research center. PARTICIPANTS:
      People (N=23) with chronic SCI (>1 y) who were participating in a weight loss
      study to compare the effectiveness of diet only (1000 kcal/d for 12 wk) versus
      diet with arm crank ergometry (1000 kcal/d and arm crank ergometry 3 times a week
      for 12 wk). INTERVENTION: Arm crank ergometry. MAIN OUTCOME MEASURE: Changes in
      shoulder pain intensity using the Wheelchair User's Shoulder Pain Index (WUSPI).
      RESULTS: After adjusting for baseline scores, there was no significant difference
      between the 2 groups on postintervention WUSPI scores (F(1,20)=.85, P=.37,
      partial eta2=.04). The strength of the relationship between group assignment
      (diet only vs diet and arm crank ergometry) and final WUSPI score was weak, as
      assessed by a partial eta2, with group assignment accounting for 4% of the
      variance on the WUSPI. The adjusted means were lower in the diet and arm crank
      ergometry group (mean, 7.84) than in the diet only group (mean, 12.22); however,
      these differences did not appear to be clinically significant. CONCLUSIONS: A
      primary fitness program using arm crank ergometry does not increase shoulder pain
      in people with SCI who use wheelchairs. Further investigation with a larger group
      and what constitutes clinically significant changes on the WUSPI is warranted to
      confirm our results.

PMID- 18047894
TI  - The S1 "Scotty dog": report of a technique for S1 transforaminal epidural steroid
      injection.
AB  - OBJECTIVE: To report a technique for needle placement by using the bony landmark
      of the "Scotty dog" on an oblique view for epidural injection of corticosteroid
      into the S1 foramina. DESIGN: Brief report on a technique for S1 transforaminal
      epidural steroid injection. SETTING: Academic multispecialty spine center.
      PARTICIPANTS: Patients with L5 and S1 foraminal and paracentral disk herniation
      with concurrent L5-S1 radicular pain. INTERVENTION: Fluoroscopically guided,
      contrast-enhanced L5 and S1 transforaminal epidural steroid injections (ESIs).
      MAIN OUTCOME MEASURES: Not applicable. RESULTS: The L5-S1 foramina can be
      visualized with 1 oblique (and usually caudally tilted) fluoroscopic view. An S1
      Scotty dog can be visualized as an anatomic landmark for the guidance of the
      needle tip into the S1 foramen. While performing simultaneous L5 and S1
      transforaminal ESIs, 1 view can be used to guide both needles into the foramen.
      Thus, the procedure can be completed in less time and potentially with less
      radiation exposure than if different views for each foramen were to be used.
      CONCLUSIONS: Classic description of the S1 spinal nerve block uses an
      anteroposterior approach to the foramen. Looking for an S1 Scotty dog facilitates
      predictable visualization of the foramen, medial needle placement with epidural
      flow of contrast, and simultaneous visualization for needle placement to the L5
      foramen.

PMID- 18047895
TI  - Expert opinion and controversies in musculoskeletal and sports medicine: core
      stabilization as a treatment for low back pain.
AB  - Although there are a wide variety of therapeutic exercises that have been
      proposed as treatments for low back pain (LBP), the last 20 years have seen the
      development of a substantial focus on the use of exercises that are intended to
      address intersegmental stability in the lumbar spine. These exercise programs are
      varyingly referred to as lumbar stabilization, segmental stabilization, or core
      stabilization, among other terms, and are aimed at improving the neuromuscular
      control, strength, and endurance of a number of muscles in the trunk and pelvic
      floor that are believed to play important roles in the dynamic stability of the
      spine. Although it is difficult to quantify, there appears to have been a
      tremendous degree of penetration of these treatment concepts into the therapeutic
      arena, the medical literature, and the lay press. Despite this, there are few
      prospective studies on patients with LBP, and there is even more limited
      discussion of the concepts of patient selection, dose-response, and long-term
      outcome associated with these approaches. There also is a significant lack of
      uniformity regarding the meaning of "core stabilization" and what therapeutic
      exercises may be most effective.

PMID- 18047896
TI  - Perspectives on the state-of-the-science in rehabilitation medicine and its
      implications for Medicare postacute care policies.
AB  - Better measurement of the case-mix complexity of patients receiving
      rehabilitation services is critical to understanding variations in the outcomes
      achieved by patients treated in different postacute care (PAC) settings. The
      Medicare program recognized this issue and is undertaking a major initiative to
      develop a new patient-assessment instrument that would standardize case-mix
      measurement in inpatient rehabilitation facilities, long-term care hospitals,
      skilled nursing facilities, and home health agencies. The new instrument, called
      the Continuity Assessment Record and Evaluation Tool, builds on the scientific
      advances in measurement to develop standard measures of medical acuity,
      functional status, cognitive impairment, and social support related to resource
      need, outcomes, and continuity of care for use in all PAC settings.

PMID- 18047897
TI  - Does passive cycling induce changes in peripheral blood flow in persons with
      spinal cord injury?

PMID- 18047899
TI  - Misconceptions in measuring change.

PMID- 18047902
TI  - Safety of cervical transforaminal steroid injections.

PMID- 18047904
TI  - What is "sleep-disordered breathing" for patients with neuromuscular weakness?

PMID- 18047905
TI  - Axial spinal unloading for adolescent idiopathic scoliosis.

PMID- 18047907
TI  - Effects of alcohol consumption and other lifestyle behaviors on blood pressure
      for the middle-aged and elderly in the Guangxi Hei Yi Zhuang and Han populations.
AB  - Han is the largest group and Zhuang is the largest minority among the 56 ethnic
      groups in China. Geographically and linguistically, Zhuang can be classified into
      43 ethnic subgroups, in which Hei Yi Zhuang is proved to be the most conservative
      subgroup. Little is known about the relationship between alcohol consumption and
      blood pressure levels in this population. Therefore, the present study was
      undertaken to compare the effects of alcohol consumption and other lifestyle
      behaviors on blood pressure levels for the middle-aged and elderly in the Guangxi
      Hei Yi Zhuang and Han populations. A total of 657 subjects of Hei Yi Zhuang aged
      40 and older were surveyed by a stratified randomized cluster sampling.
      Information on demography, diet, and other lifestyle factors was collected by
      standard questionnaires. Anthropometric parameters and serum lipid levels were
      also obtained in all subjects. The results were compared with those in 520
      participants of Han Chinese from the same region. The levels of systolic blood
      pressure and pulse pressure in Hei Yi Zhuang were higher than those in Han (P <
      .01-.001). Hypertension was positively correlated with sex (male), age, physical
      activity, alcohol consumption, serum triglyceride levels, and total energy, total
      fat, and salt intakes, and negatively associated with educational level in Hei Yi
      Zhuang (P < .05-.001), whereas positively correlated with sex (male), age,
      physical activity, alcohol consumption, body mass index, waist circumference,
      serum total cholesterol levels, and total energy, total fat, and salt intakes,
      and negatively associated with educational level in Han (P < .05-.001). The
      difference in blood pressure levels between the two ethnic groups might result
      from different dietary habit, lifestyle, sodium intake, educational level,
      physical activity, and even genetic factors.

PMID- 18047908
TI  - Growth hormone response to the GABA-B agonist baclofen in 3-week abstinent
      alcoholics.
AB  - Gamma-aminobutyric acid (GABA) dysfunction is a known feature of alcoholism. We
      investigated GABA-B receptor activity in 3-week abstinent alcoholics using the
      growth hormone (GH) response to baclofen, a GABA-B receptor agonist. The study
      aimed to investigate the relationship between GABA-B receptor activity and
      alcohol withdrawal. GH response to baclofen was measured in alcohol-dependent
      males without depression (n = 22) who were on day 21 of alcohol abstinence and in
      healthy control male subjects (n = 23). After 20mg baclofen was given orally to
      the subjects, blood samples for GH assay were obtained every 30 min for the
      subsequent 150 min. The patients were divided into two subgroups (continuing
      withdrawal and recovered withdrawal subgroups) according to their withdrawal
      symptom severity scores on day 21 of alcohol cessation. Baclofen administration
      significantly altered GH secretion in the controls, but not in the patients. When
      GH response to baclofen was assessed as DeltaGH, it was lower in the patients
      with continuing withdrawal symptoms than in the controls and in the recovered
      withdrawal group. Impaired GH response to baclofen in all patients mainly
      pertained to the patients whose withdrawal symptoms partly continued. Our results
      suggest that reduced GABA-B receptor activity might be associated with longer
      term alcohol withdrawal symptoms in alcoholic patients.

PMID- 18047909
TI  - Short-term selection for acute ethanol tolerance and sensitization from an F2
      population derived from the high and low alcohol-sensitive selectively bred rat
      lines.
AB  - Previous studies have identified quantitative trait loci (QTL) in the inbred high
      and low alcohol-sensitive rat (IHAS1 and ILAS1) strains. The original development
      of the strains involved selection for ethanol sensitivity based on duration of
      the loss of the righting reflex (LORR) after a standard dose of ethanol. This
      paper confirms some of these QTL using a short-term selection procedure based on
      the difference between the blood ethanol level at LORR and regain of the righting
      response. An F(2) population of rats was developed by a reciprocal cross of IHAS1
      and ILAS1 rats. Selection for five generations was carried out using delta-blood
      ethanol concentration (dBEC) as the selection trait, where dBEC=BECLR (BEC at
      loss of righting reflex)-BECRR (BEC at regain of righting reflex). The lines were
      labeled tolerant (TOL) or sensitive (SENS). Approximately one-third of the
      offspring for each generation in each line were genotyped using DNA markers that
      had been previously found to be linked to QTL on chromosomes 1, 2, 5, 12, and 13.
      By the fifth generation of selection, the lines showed a very large difference in
      dBEC, BECRR, and duration of LORR; BECLR showed little segregation during the
      selection, and latency to lose the righting reflex showed none. IHAS allele
      frequency increased in the SENS line for markers on chromosomes 1, 5, 12, and 13
      while ILAS allele frequency increased in the TOL line. These results were in good
      agreement with the two previous QTL studies. On chromosome 2, the selection
      resulted in an accumulation of ILAS alleles in both lines. This study provides
      independent confirmation of the location of QTL on chromosomes 1, 5, 12, and 13
      for ethanol sensitivity. It also suggests that genetic differences in duration of
      LORR are mediated primarily by the dBEC phenotype.

PMID- 18047910
TI  - Prenatal ethanol exposure alters core body temperature and corticosterone rhythms
      in adult male rats.
AB  - Ethanol's effects on the developing brain include alterations in morphology and
      biochemistry of the hypothalamus. To examine the potential functional
      consequences of ethanol's interference with hypothalamic differentiation, we
      studied the long-term effects of prenatal ethanol exposure on basal circadian
      rhythms of core body temperature (CBT) and heart rate (HR). We also examined the
      late afternoon surge in corticosterone (CORT). Core body temperature and HR
      rhythms were studied in separate groups of animals at 4, 8, and 20 months of age.
      The normal late afternoon rise in plasma CORT was examined in freely moving male
      rats at 6 months of age via an indwelling right atrial cannula. Results showed
      that the CBT circadian rhythm exhibited an earlier rise after the nadir of the
      rhythm in fetal alcohol-exposed (FAE) males at all ages compared to controls. At
      8 months of age, the amplitude of the CBT circadian rhythm in FAE males was
      significantly reduced to the level observed in controls at 20 months. No
      significant effects of prenatal ethanol exposure were observed on basal HR rhythm
      at any age. The diurnal rise in CORT secretion was blunted and prolonged in 6
      month-old FAE males compared to controls. Both control groups exhibited a robust
      surge in CORT secretion around the onset of the dark phase of the light cycle,
      which peaked at 7:30 p.m. Whereas FAE males exhibited a linear rise beginning in
      mid afternoon, which peaked at 9:30 p.m. These results indicate that exposure to
      ethanol during the period of hypothalamic development can alter the long-term
      regulation of circadian rhythms in specific physiological systems.

PMID- 18047911
TI  - Ethnic differences in the association of birth weight and blood pressure: the
      Georgia cardiovascular twin study.
AB  - BACKGROUND: African Americans (AAs) not only have higher blood-pressure levels,
      but also an increased risk of low weight at birth, compared with European
      Americans (EAs). In light of fetal programming theories, it has been suggested
      that ethnic differences in blood pressure originate in utero. However, most
      previous studies in biethnic samples have not found a significant inverse
      association between birth weight and blood pressure in AAs. METHODS: In 562 EA
      and 465 AA adolescent twins of the Georgia Cardiovascular Twin Study, we
      investigated the potential ethnic difference in the association of blood pressure
      and birth weight, with the ability to control for potential confounding by
      familial factors. RESULTS: Blood-pressure levels were significantly higher in AAs
      compared to EAs, independent of birth weight (P < .01). After adjustment for
      parental factors and body mass index, the difference in systolic blood pressure
      per kg birth weight was -1.1 mm Hg (95% confidence interval, -2.7 to 0.48, P =
      .17) in EAs, and -2.5 mm Hg (95% confidence interval, -4.7 to -0.40, P = .02) in
      AAs. A significant ethnic interaction was revealed in paired analysis, where the
      inverse association remained in AAs, but not in EAs. Associations with diastolic
      blood pressure were generally weaker and nonsignificant. CONCLUSIONS: We showed
      that low birth weight was associated with an elevated systolic blood pressure in
      AAs, independent of familial factors. The results also suggest that the
      association between birth weight and blood pressure may be more pronounced in AAs
      in adolescence.

PMID- 18047912
TI  - Occupational, commuting, and leisure-time physical activity in relation to
      cardiovascular mortality among finnish subjects with hypertension.
AB  - BACKGROUND: The association between different types of physical activity and
      cardiovascular risk among hypertensive subjects is not fully understood. The
      purpose of this study was to determine the association of occupational,
      commuting, and leisure-time physical activity on cardiovascular mortality among
      hypertensive patients. METHODS: Study cohorts included 26,643 hypertensive
      Finnish men and women who were aged 25 to 64 years and free of coronary heart
      disease, stroke, and Type 1 diabetes. RESULTS: During a mean follow-up of 19.9
      years (range, 6.6 to 31.7 years), 3743 subjects died because of cardiovascular
      disease. The multivariate-adjusted (age, study year, education, alcohol
      consumption, smoking, body mass index, systolic blood pressure, total
      cholesterol, use of antihypertensive drugs, and diabetes at baseline or during
      follow-up, and the other two kinds of physical activity) hazard ratios of
      cardiovascular mortality associated with low, moderate, and high occupational
      physical activity were 1.00, 0.84, and 0.86 (P for trend = .006), respectively,
      for hypertensive men, and 1.00, 0.85, and 0.84 (P for trend = .014),
      respectively, for hypertensive women. The multivariate-adjusted hazard ratios of
      cardiovascular mortality associated with low, moderate, and high leisure-time
      physical activity were 1.00, 0.84, and 0.73 (P for trend < .001), respectively,
      for hypertensive men, and 1.00, 0.78, and 0.76 (P for trend < .001),
      respectively, for hypertensive women. Active commuting to and from work was
      significantly associated with reduced cardiovascular mortality in hypertensive
      women. CONCLUSIONS: Moderate or high levels of occupational or leisure-time
      physical activity reduce cardiovascular mortality among both men and women with
      hypertension. Walking or cycling to and from work daily reduces cardiovascular
      mortality among hypertensive women.

PMID- 18047913
TI  - Beta-adrenergic receptor genes are associated with arterial stiffness in black
      and white adults: the Bogalusa Heart Study.
AB  - BACKGROUND: Sympathetic nervous activity, which is regulated by the beta
      adrenergic receptor (beta-AR), is an important determinant of the arterial wall
      stiffening process. This study examines the genetic influence of beta-AR gene
      polymorphisms (beta(1)-AR Arg389Gly, beta(2)-AR Arg16Gly, and beta(3)-AR
      Trp64Arg) on arterial stiffness in black and white young adults. METHODS: The
      study cohort included 366 black and 891 white adults, aged 19 to 44 years,
      enrolled in the Bogalusa Heart Study. Aorta-femoral pulse-wave velocity (af-PWV)
      was measured by echo-Doppler in a subsample (n = 614). RESULTS: Pulse pressure
      and heart rate were significantly associated with af-PWV in both races, but not
      with the three polymorphisms. The af-PWV values differed significantly among the
      beta(1)-AR Arg389Gly genotype groups in whites (P = .007) and in the total sample
      (P = .005), with those who were homozygous for Gly389 showing higher values than
      those who were homozygous for Arg389, after adjusting for cardiovascular risk
      factors. The beta(3)-AR Arg64 allele was associated with higher af-PWV values in
      blacks (P = .022) and in the total sample (P = .015). The beta(2)-AR Arg16 allele
      was associated with af-PWV only in blacks (P = .020). In multivariate regression
      analysis for the total sample, age, pulse pressure, heart rate, beta(1)-AR
      Arg389Gly, beta(3)-AR trp64Gly, and smoking status were, in descending order,
      associated with af-PWV. Furthermore, af-PWV values significantly increased with
      the increasing number of beta(1)-AR Gly389, beta(2)-AR Arg16, and beta(3)-AR
      Arg64 alleles (P for trend = .0003). CONCLUSIONS: These results indicate that the
      beta-AR gene polymorphisms influence arterial stiffness in black and white young
      adults in an additive manner.

PMID- 18047914
TI  - Prevalence and persistence of masked hypertension in treated hypertensive
      patients.
AB  - BACKGROUND: Masked hypertension (MH) is defined as a normal blood pressure in the
      physician's office and an elevated blood pressure when measured out-of-office.
      The cause of MH may be termed the masked hypertension effect (MHE), and is not
      restricted to blood-pressure (BP) values around the thresholds for normal BP. We
      investigated the prevalence and persistence of MH and MHE in patients who were
      being treated for high BP and who had been followed for a period of 1 year.
      METHODS: One hundred and sixty-one treated hypertensive patients underwent office
      blood-pressure measurements (OBPMs) at seven visits and self-performed blood
      pressure measurements (SBPMs) for 1 week before each visit over a period of 1
      year. All measurements were performed with the same type of automatic device. At
      each visit, MH was determined according to the European Society of Hypertension
      definition (OBPM, <140/90 mm Hg; SBPM, >/=135 mm Hg or 85 mm Hg). In addition, we
      determined prevalences of MHE at 5/3 mm Hg (SBPM exceeds OBPM by 5 mm Hg systolic
      and 3 mm Hg diastolic), and MHE at 10/6 mm Hg (SBPM exceeds OBPM by 10 mm Hg
      systolic and 6 mm Hg diastolic), respectively. RESULTS: During the entire study,
      50% of the patients had MH, and 40% had MHE at 5/3 mm Hg at least once. At four
      sequential OBPM visits, 2% consistently had MH, and 3% had MHE at 5/3 mm Hg or
      MHE at 10/6 mm Hg. The prevalence of MH increased with lower OBPM levels but
      remained rather constant for MHE at 5/3 mm Hg and MHE at 10/6 mm Hg. The
      persistence of MH and the MHE over time in individual patients was low.
      CONCLUSIONS: We conclude that MH and MHE at 5/3 mm Hg and MHE at 10/6 mm Hg
      commonly occur in treated patients, but are not persistent phenomena and probably
      result from an accidentally low OBPM value on one particular occasion.

PMID- 18047915
TI  - The Odyssey of Masked Hypertension in the HOMERUS Trial.

PMID- 18047916
TI  - Changes in self-monitored pulse pressure correlate with improvements in B-type
      natriuretic Peptide and urinary albumin in treated hypertensive patients.
AB  - BACKGROUND: Pulse pressure (PP) is an independent marker of cardiovascular risk,
      even in treated hypertensive subjects, but is often little changed by
      antihypertensive treatment. We assessed the hypothesis that changes in PP during
      antihypertensive therapy correlate with changes in surrogate markers of target
      organ damage. METHODS: We studied 540 treated hypertensive subjects whose home
      systolic blood pressure (SBP) was >/=135 mm Hg. They were followed for 6 months
      after allocation to either a control group or an added treatment group
      (doxazosin, 1 to 4 mg plus beta-blocker when needed). The changes in PP and
      various blood pressure (BP) measures, including mean BP (MP), SBP, and diastolic
      BP (DBP) during follow-up, were related to changes in plasma B-type natriuretic
      peptide (BNP) and the urine albumin-creatinine ratio (UAR). RESULTS: Although
      self-measured MP was significantly lowered in the added treatment group, PP was
      not changed overall, although some patients showed a decrease, and others showed
      an increase. In multivariable analyses, changes in both clinic and home PP were
      positively associated with changes in log BNP, such that increases in clinic and
      home PP were paralleled by corresponding increases in BNP. However, no such
      corresponding relationships were observed when home PP decreased. The change in
      home PP, but not clinic PP, was positively and linearly associated with the
      change in UAR. CONCLUSIONS: Changes in PP during antihypertensive treatment are
      important because PP may increase in some patients, in whom there are adverse
      changes in surrogate markers of target-organ damage. These changes of PP are best
      evaluated by home monitoring.

PMID- 18047917
TI  - Mild hyperuricemia and subclinical renal damage in untreated primary
      hypertension.
AB  - BACKGROUND: Subclinical renal damage and hyperuricemia are not uncommon in
      patients with primary hypertension. Whether mild hyperuricemia reflects a
      subclinical impairment of renal function or contributes to its development is
      currently debated. We investigated the relationship between serum uric-acid
      levels and the occurrence of early signs of kidney damage. METHODS: Four hundred
      eighteen patients with primary hypertension were studied. Albuminuria was
      measured as the albumin-to-creatinine ratio, and creatinine clearance was
      estimated by the formula of Cockcroft and Gault. Interlobar resistive index and
      renal abnormalities, ie, the renal volume-to-resistive index ratio, were
      evaluated by renal Doppler and ultrasound. RESULTS: Uric acid was directly
      related to resistive index (P = .007) in women and to albuminuria (P = .04) in
      men, and was inversely related to the renal volume-to-resistive index ratio in
      both men (P = .005) and women (P = .02). Patients with uric-acid levels above the
      median showed a higher prevalence of microalbuminuria (14% v 7%, P = .012) and of
      renal abnormalities (41% v 33%, P = .007). Moreover, when creatinine clearance
      was taken as a covariate, patients with increased uric-acid levels showed higher
      albuminuria and resistive indices, and a lower renal volume-to-resistive index
      ratio. Even after adjustment for several risk factors, each standard deviation
      increase in serum uric acid entailed a 69% higher risk of microalbuminuria, and a
      39% greater risk of ultrasound detectable renal abnormalities. CONCLUSIONS: Mild
      hyperuricemia is associated with early signs of renal damage, ie,
      microalbuminuria and ultrasound-detectable abnormalities, regardless of the
      glomerular filtration rate in primary hypertension.

PMID- 18047918
TI  - Determinants of reduction of coronary flow reserve in patients with type 2
      diabetes mellitus or arterial hypertension without angiographically determined
      epicardial coronary stenosis.
AB  - BACKGROUND: Coronary flow reserve (CFR) may be reduced even in the absence of
      coronary artery disease. We investigated the determinants of CFR impairment in
      Type 2 diabetes mellitus (DM2) and in arterial hypertension (HTN) without
      epicardial coronary artery stenosis. METHODS: Twenty-eight patients with DM2 and
      27 with HTN, both with normal coronary angiography, and 18 healthy controls
      underwent transthoracic echocardiography, including Doppler recording of the
      distal left anterior descending artery, at rest as well as after high-dose
      dipyridamole. Coronary flow reserve was calculated as the hyperemic to resting
      coronary diastolic peak velocities ratio. RESULTS: The three groups were
      comparable for sex, age, and heart rate. Systolic and mean blood pressures were
      higher in DM2 and HTN patients than in control subjects. Diabetic and
      hypertensive patients had a higher left-ventricular mass index (LVMi) and
      relative wall thickness, impaired diastolic indexes, and lower CFR compared with
      control subjects (P = .02 and P = .03, respectively) because of lower hyperemic
      coronary velocity (P = .005 and P = .004, respectively). After a multilinear
      regression analysis (using age, sex, HTN status, DM2 status, smoking, total
      cholesterol/HDL-cholesterol ratio, and LVMi as potential determinants), the LVMi
      increase was the main predictor of the reduction of CFR, adjusted for mean BP (P
      < .0001), in the pooled population, with a minor contribution of age (P = .03),
      HTN status (P = .02), and DM2 status (P = .03). CONCLUSIONS: In Type 2 DM and HTN
      without epicardial coronary stenosis, an impairment of CFR is demonstrable. This
      is partly explained by an increased left-ventricular mass, able to condition the
      hyperemic stimulation of myocardial blood flow.

PMID- 18047919
TI  - Prognostic relevance of metabolic syndrome in hypertensive patients at low-to
      medium risk.
AB  - BACKGROUND: The prognostic impact of metabolic syndrome (MetS) in the
      hypertensive population at low-medium risk is unknown. In this study, we
      evaluated the prognostic relevance of MetS in hypertensive patients at low-medium
      risk. METHODS: The occurrence of nonfatal and fatal cardiac and cerebrovascular
      events was evaluated in 802 patients with mild to moderate essential hypertension
      at low-medium risk according to the 2003 World Health Organization/International
      Society of Hypertension statement on the management of hypertension. Among these
      patients, 218 (27.2%) had MetS according to a modified National Cholesterol
      Education Program Adult Treatment Panel III (NCEP ATP III) definition (body mass
      index in place of waist circumference). RESULTS: During follow-up (6.9 +/- 3.1
      years; range, 0.5 to 13.1 years, mean +/- SD), 58 first cardiovascular events
      occurred. The event rates per 100 patient-years in patients without and with MetS
      were 0.87 and 1.51, respectively. Event-free survival was significantly different
      between groups (P = .03). After adjustment for several covariates, Cox regression
      analysis showed that cardiovascular risk was significantly higher in patients
      with than in patients without MetS (relative risk, 2.64; 95% confidence interval,
      1.52 to 4.58; P = .001). Other independent predictors of outcome were age,
      smoking habit, 24-h systolic BP, and LDL cholesterol. CONCLUSIONS: Hypertensive
      patients at low-medium risk with MetS are at higher cardiovascular risk than
      those without MetS. Metabolic syndrome may be a useful tool for clinicians to
      identify subjects who are at increased risk when traditional assessment may
      indicate low-medium risk.

PMID- 18047920
TI  - Uncoupled endothelial nitric oxide synthase and oxidative stress in a rat model
      of pregnancy-induced hypertension.
AB  - BACKGROUND: Preeclampsia is a human pregnancy-associated syndrome associated with
      hypertension, proteinuria, and endothelial dysfunction. We tested whether
      increased reactive oxygen species (superoxide and peroxynitrite) production and
      decreased bioavailability of the endothelial nitric oxide (NO) synthase (eNOS)
      cofactor tetrahydrobiopterin (BH4) contributes to maternal endothelial
      dysfunction in rats with pregnancy-induced hypertension and several
      characteristics of preeclampsia. METHODS: Nonpregnant (DS) and pregnant (PDS)
      rats were treated with deoxycorticosterone acetate and 0.9% saline for
      approximately 3 weeks and nonpregnant (Con) and pregnant (P) rats received tap
      water. Blood pressure, urinary protein levels, mesenteric vascular reactivity,
      aortic protein expression, and aortic reactive oxygen species levels were
      compared between the four groups. RESULTS: The PDS rats had significantly
      decreased mesenteric endothelium-dependent relaxation responses and aortic NO
      production compared to Con, DS, and P rats despite increased aortic eNOS
      expression. Aortic superoxide and peroxynitrite levels were increased in PDS rats
      compared with Con, DS, and P rats. Scavenging of reactive oxygen species or
      increasing tetrahydrobiopterin levels normalized mesenteric endothelium-dependent
      relaxation responses, aortic NO production, and aortic superoxide and
      peroxynitrite levels in PDS rats. CONCLUSIONS: These data suggest that increased
      superoxide production by NADPH oxidase, peroxynitrite degradation of BH4, and
      uncoupled eNOS contribute to endothelial dysfunction in a rat model of pregnancy
      induced hypertension.

PMID- 18047921
TI  - Effect of telmisartan on forearm postischemic hyperemia and serum asymmetric
      dimethylarginine levels.
AB  - BACKGROUND: Although telmisartan may be more beneficial for glucose metabolism
      than other angiotensin II receptor blockers (ARBs), it has not been determined
      whether telmisartan exerts more favorable effects on biological and functional
      parameters related to endothelial function than other ARBs. METHODS: A study with
      a crossover design was conducted in 40 hypertensive patients (61 +/- 10 years
      old, mean +/- SD) who had previously been treated with ARBs other than
      telmisartan or valsartan (ie, ARBs were switched to either telmisartan 40 mg/day
      or valsartan 80 mg/day, administered alternately for 12 weeks each). Blood
      examinations were conducted, and the mean reactive hyperemia ratio (mRHR) was
      measured by plethysmography for each treatment regimen. RESULTS: There were no
      significant differences in either blood pressure or plasma levels of monocyte
      chemoattractant protein-1, C-reactive protein, 3-nitrotyrosine, or vascular cell
      adhesion molecule-1 between the two treatment regimens. The mRHR (2.7 +/- 1.0 v
      2.4 +/- 1.0, mean +/- SD) was larger (P < .05), and the plasma levels of
      asymmetric dimethylarginine (ADMA) (0.45 +/- 0.08 v 0.50 +/- 0.17 micromol/L,
      mean +/- SD) and the homeostasis model assessment index of insulin resistance
      (HOMA-IR) (2.3 +/- 1.6 v 2.8 +/- 2.1, mean +/- SD) were lower (P < .05) in
      telmisartan-treated patients than in valsartan treated patients. The percent
      change in ADMA, but not in HOMA-IR, correlated significantly with that in the
      mRHR (beta = -0.33, t value = -2.00, P = .04). CONCLUSIONS: At doses producing
      equivalent hypotensive effects, telmisartan apparently had a more favorable
      effect on functional parameters related to endothelial function than did
      valsartan. The reduction in plasma ADMA levels may contribute to this more
      favorable effect of telmisartan.

PMID- 18047922
TI  - Change in forearm reactive hyperemia after telmisartan: an endothelial effect?

PMID- 18047923
TI  - Self-measurement and self-titration in hypertension: a pilot telemedicine study.
AB  - BACKGROUND: Because of poor patient compliance and clinical inertia, hypertension
      control rates remain poor. Home blood-pressure measurements (HBPM) improve
      compliance of patients and achievement of blood pressure (BP) targets. However,
      few studies have evaluated self-BP management by patients. METHODS: In a
      multicenter, prospective, single-group, open-label pilot study of 111 patients
      whose hypertension was uncontrolled despite monotherapy, we studied satisfaction
      with, and feasibility of, HBPM and self-titration of antihypertensive treatment
      using telemedicine for compliance, efficacy, and safety. After education
      (protocol, action plan, and use of the HBPM device), patients performed a
      sequence of HBPM every 2 weeks for 8 weeks. Following a stepwise approach,
      treatment was increased by the patient at weeks 4 and 6 if average HBPM values
      exceeded predefined limits. For each titration, the patient informed the Core
      Center by telemedicine, but BP values were transferred automatically. RESULTS:
      Overall, 80% of patients were satisfied (58%) or very satisfied (23%) with the
      program (95% confidence interval, 73% to 87%). Regarding compliance, 78% of
      patients fully complied with self-measurement, and just over 71% titrated their
      treatment adequately. Physicians were satisfied (52%) or very satisfied (22%)
      with the program. Between the first and final visits (at week 8), office
      systolic/diastolic BP (mean +/- SD) decreased significantly from 151 +/- 9/91 +/-
      6 to 143 +/- 13/84 +/- 11 mmHg. During the trial, HBPM (mean +/- SD) decreased
      significantly from 149 +/- 13/86 +/- 12 to 138 +/- 16/81 +/- 10 mmHg. No
      significant safety issues were reported. CONCLUSIONS: This innovative approach to
      the management of hypertension, combining self-measurement and self-titration, is
      feasible, well-accepted by both patients and physicians, and safe.

PMID- 18047924
TI  - Prevention of hypertension, cardiovascular damage and endothelial dysfunction
      with green tea extracts.
AB  - BACKGROUND: We investigated the effect of green tea extract (GTE) in arterial
      hypertension with high oxidative stress. Angiotensin (Ang) II induces endothelial
      dysfunction (ED) that is crucial for the development of atherosclerosis and
      hypertension. METHODS: Male Sprague-Dawley rats, 13 weeks old, randomly assigned
      to drinking water with or without GTE (6 mg/mL) received a vehicle, a high (700
      microg/kg/d) or a low (350 microg/kg/d) Ang II dose for 13 days, by osmotic mini
      pumps. Blood pressure (BP) was measured with telemetry. After sacrifice, left
      ventricular (LV) mass index, small mesenteric artery media-to-lumen ratio, and
      concentration-response curves of phenylephrine-precontracted arteries to
      acetylcholine were evaluated. The effect of the superoxide dismutase (SOD-1)
      analog tempol on artery responses to acetylcholine was assessed. Oxidative stress
      was measured by plasma hydroperoxides and nitrotyrosine levels. The mRNA of heme
      oxygenase 1 (HO-1), NADPH oxidase endothelial p22(phox) subunit, and SOD-1 was
      also measured in the aorta. RESULTS: Compared with vehicle high Ang II increased
      BP, LV mass index, media-to-lumen ratio, and hydroperoxide radicals. The GTE
      blunted these increases, prevented the increase in HO-1, p22(phox), and SOD-1
      mRNA in aorta caused by Ang II, and reduced them below baseline levels. Low Ang
      II dose increased BP values and plasma hydroperoxides only during the first week.
      Both Ang II doses shifted rightward the curves to acetylcholine; this was
      prevented in vivo by GTE and abolished in vitro by tempol. CONCLUSIONS: The GTE
      prevented hypertension and target organ damage induced by a high Ang II dose,
      likely by prevention or scavenging of superoxide anion generation.

PMID- 18047925
TI  - Aldosterone breakthrough during angiotensin II receptor blockade in hypertensive
      patients with diabetes mellitus.
AB  - BACKGROUND: Aldosterone is an important pathogenetic factor, independent of the
      renin-angiotensin system in cardiovascular and renal disease. Aldosterone
      breakthrough during angiotensin-converting enzyme (ACE) inhibitor therapy was
      reported in hypertension, diabetes mellitus, and chronic renal disease. It is
      unclear whether the angiotensin II receptor blocker (ARB) causes aldosterone
      breakthrough in patients with hypertension and diabetes mellitus, and whether
      aldosterone breakthrough contributes to renal injury in these patients. METHODS:
      We prospectively studied 95 hypertensive patients with diabetes mellitus.
      Patients were treated with candesartan (8 mg/day, n = 47) or valsartan (80
      mg/day, n = 48) for 15 months. Blood pressure (BP), urinary albumin excretion
      (UAE), biochemical markers, plasma aldosterone concentration (PAC), and plasma
      renin activity (PRA) were measured before and at 3, 6, 12, and 15 months of
      treatment. Nine patients who exhibited aldosterone breakthrough after treatment
      with ARB were placed on spironolactone (25 mg/day) for 3 months, and BP, UAE, and
      biochemical markers were measured after treatment. RESULTS: Although the overall
      PAC was significantly decreased (P < .05) in each group, it eventually increased
      in 21 (candesartan, 11 patients; valsartan, 10 patients) of 95 patients (22%;
      aldosterone breakthrough). Blood pressure, PRA, and biomedical markers did not
      differ between the two groups during treatment. Although UAE was significantly
      decreased in patients with or without aldosterone breakthrough at 6 months, it
      was increased again at 15 months of treatment in patients with aldosterone
      breakthrough. Treatment with spironolactone markedly reduced UAE in these
      patients. CONCLUSIONS: Aldosterone breakthrough was seen to be equal in
      hypertensive patients with diabetes mellitus treated with candesartan or
      valsartan. Aldosterone blockade therapy may be effective in preventing renal
      injury in hypertensive patients with aldosterone breakthrough.

PMID- 18047926
TI  - Laboratory diagnosis of primary aldosteronism, and drospirenone-ethinylestradiol
      therapy.
AB  - BACKGROUND: Primary aldosteronism is recognized as the most frequent cause of
      secondary hypertension. Screening for primary aldosteronism by determination of
      the aldosterone-to-renin ratio (ARR) is much more frequently performed in current
      practice. However, most antihypertensive medications interfere with ARR
      determination, and although verapamil and alpha-adrenergic blockers are
      considered sufficiently neutral, the specific drugs which should be discontinued
      before ARR screening are a matter of debate. Our objective was to evaluate the
      possible interference of a new progestin with antimineralocorticoid activity
      (drospirenone) on the determination of ARR and the diagnosis of primary
      aldosteronism. METHODS AND RESULTS: We describe an instance of a false-positive
      laboratory diagnosis of primary aldosteronism (by both screening and confirmatory
      test) in a normotensive 34-year-old healthy woman taking Yasmin (drospirenone +
      ethinylestradiol) (Shering S.p.A., Milan, Italy). Subsequent ARR values during
      Yasmin therapy changed during the menstrual cycle (days 7, 14, 21, and 28 were
      tested), reaching values above the screening ARR threshold that led to a
      suspicion of primary aldosteronism just before menses. In contrast, during a drug
      free menstrual cycle, the ARR remained constantly below the screening ARR
      threshold. CONCLUSIONS: We report for the first time that drospirenone may
      interfere with laboratory screening and confirmatory testing for the diagnosis of
      primary aldosteronism. As a consequence, this drug should be withdrawn in
      hypertensive women investigated for secondary hypertension. Although drospirenone
      was demonstrated to possess antihypertensive properties when taken as
      postmenopausal hormonal replacement therapy, its use for contraceptive purposes
      needs to be more carefully investigated.

PMID- 18047927
TI  - Activated cells in urine and monocyte chemotactic peptide-1 (MCP-1)--sensitive
      rejection markers in renal graft recipients.
AB  - Chemokines induced during an acute immune alloresponse cause cellular
      infiltration of the allograft. These chemokines and cells are excreted with
      urine. The aim of the study was to assess the diagnostic utility of urinary
      excretion of monocyte chemotactic peptide-1 and certain cells involved in
      infiltration i.e. CD3+, CD64+ and HLA-DR+ cells. The study entailed 35 patients
      with acute renal rejection and 65 with a stable graft function. Urinary sediments
      were prepared by means of cytospin and stained with anti-CD3, anti-CD64, anti-HLA
      DR labeled monoclonal antibodies. Urinary expression of MCP-1 was assayed by
      ELISA. In the patients with acute rejection MCP-1 level was ten-fold higher than
      in the patients with a stable graft function (6.1+/-3.4 vs 0.6+/-0.4 ng/mg
      creatinine). The number of CD3+ cells was over 5 times higher than in the non
      rejection patients (13.4+/-4.6 vs 2.5+/-2.2). The number of HLA-DR+ cells was 6
      times higher in the acute rejection patients (15.7+/-5.9 vs 2.5+/-2.7). The
      number of CD64+ cells was significantly increased in the patients during an acute
      rejection episode (p<0.0001). CD3+, HLA-DR+ and CD64+ cell counts strongly
      correlated with urine excretion of MCP-1. The counts of CD3+ and HLA-DR+ cells
      correlated with Banff score. The assessment of MCP-1 as well as CD3+, CD64+ and
      HLA-DR+ cells can provide a useful non-invasive device for the diagnosis of acute
      rejection. A sole assay of HLA-DR+ cell excretion provides enough specificity and
      sensitivity for the routine monitoring of patients after kidney transplantation,
      saving costs and time.

PMID- 18047928
TI  - Steady state dendritic cells with forced IDO expression induce skin allograft
      tolerance by upregulation of regulatory T cells.
AB  - Despite recent extensive studies, the molecular mechanism through which DCs
      induce allograft tolerance largely remains poorly understood. In the current
      study, we presented strong evidence supporting a role for IDO in DC-mediated
      allograft tolerance. Pre-treatment of recipient mice with IDO-transduced donor
      specific BMDCs induced skin allograft tolerance in an antigen-dependent manner.
      Our data suggest that IDO-expressing DCs may regulate a delicate balance of
      cytokines that favors the differentiation of naive CD4+ T cells into Tregs
      instead of CD4+ effector T cells. In addition, BMDCs with forced IDO expression
      also have higher capability to expand natural Tregs. In consistent with the
      observation of augmented Tregs detected in the recipient mice, the capacity for
      splenic T cell alloresponse was significantly reduced in recipient mice pre
      treated with IDO-transduced BMDCs. Furthermore, the expression of inflammatory
      cytokines such as IL-2, IFNgamma, IL-6, IL-17A and IL-23p19, in splenic T cells
      of these recipient mice, was significantly lower as compared to that of recipient
      mice pre-treated with either GFP-transduced BMDCs or untransduced BMDCs.

PMID- 18047929
TI  - Heat preconditioning ameliorates hepatocyte viability after cold preservation and
      rewarming, and modulates its immunoactivity.
AB  - BACKGROUND: Heat preconditioning significantly preserved liver graft function
      after cold preservation in animal experimental model. The elevation of heat shock
      protein 70 (HSP70) was claimed to play a critical role in protecting grafts
      against cold preservation-induced hepatocyte apoptosis. However, little is known
      about whether HSP70 also plays an immunomodulatory role in cold preserved cells.
      This study aimed at investigating the relationship between HSP70 protein and the
      immunoactivity in response to lipopolysaccharide (LPS) stimulation. METHODS AND
      RESULTS: A normal rat hepatocyte cell line was preserved with University of
      Wisconsin (UW) solution, Ringer's lactate solution (RL), and phosphate-buffered
      saline (PBS) at 4 degrees C. No significant morphological alteration was noted in
      UW-preserved cells after 24 h through phase-contrast microscopic observation and
      fluorescent viability stain. Western blotting showed a two-fold increase in the
      ratio of HSP70/Bax proteins in cells after 24 h of UW preservation. Heat
      preconditioning significantly enhanced the recovery of lactate dehydrogenase
      (LDH) activity in both RL- and UW-preserved cells that were stored for a period
      of 12 h or less. Moreover, heat preconditioning promoted HSP70 and NF-kappaB p50
      nuclear translocation and suppressed the LPS-induced nuclear p50 accumulation in
      cells before UW preservation. Immunofluorescent stain revealed that the LPS
      induced p50 protein redistribution to nuclear membrane might contribute to NF
      kappaB activation, while heat preconditioning and UW cold preservation completely
      abrogated the p50 intranuclear redistribution. Thus NF-kappaB p50 might be
      responsible for the endotoxin tolerance induction. CONCLUSIONS: These findings
      strongly suggest that heat preconditioning not only preserves hepatocyte
      viability after cold preservation and rewarming, but also ameliorates its
      immunoactivity.

PMID- 18047930
TI  - CMV increases tubular apoptosis through the TNF-alpha-TNF-R1 pathway in a rat
      model of chronic renal allograft rejection.
AB  - INTRODUCTION: Destruction of transplanted kidneys through chronic allograft
      nephropathy [CAN], also known as chronic rejection, is the greatest obstacle in
      successful kidney transplantation. Causes behind CAN are many, from pre
      transplant causes to infections. Viral infections, especially CMV, are a risk
      factor for chronic rejection. We have previously developed a rat kidney
      transplant model, in which CMV enhances the development of chronic rejection
      under triple drug treatment. In this model we have now further studied the routes
      of apoptosis in virus induced early CAN vs. the routes of apoptosis in a later
      developing non-infectious CAN. MATERIALS AND METHODS: Renal transplantations were
      performed in a strain combination of DA/BN under immunosuppression. One group of
      animals was infected with RCMV and the other was left uninfected. The grafts were
      harvested on days 3-40 after transplantation. Apoptotic cells were visualised by
      in situ terminal transferase mediated dUTP nick end labelling [TUNEL] from
      paraffin embedded, formalin fixed kidney grafts. Cytokines were labelled
      imunohistochemically from frozen sections, among them tumour necrosis factor
      alpha [TNF-alpha] and its receptor-protein 1 [TNF-R1] as well as CD 95 [FAS],
      caspase 3 and CD14. The results were semi-quantitatively scored from 0 to 3+ over
      various tissues structures separately. RESULTS: In the CMV infected grafts, we
      could demonstrate a more intense TUNEL reaction in tubular epithelium [2.0+/-1.0
      vs. 0.8+/-0.5 at day 14, P<0.05] as well as an earlier increase in the expression
      TNF-alpha in the vascular endothelium [2.0+1.0 vs. 0.0+0.0 at days 3-5, P<0.05]
      than in the non-infected group. There was also an earlier increase in the tubular
      TNF-R1 expression [2.2+0.8 vs. 1.0+0.0 at days 5-7, P<0.05]. There was no
      difference in the expression of CD14, caspase 3 or FAS between the groups.
      CONCLUSIONS: CMV enhanced development of CAN was associated with tubular
      apoptosis and concomitant increase of TNF-alpha-TNF-R1, rather than the FAS-FAS
      ligand activation.

PMID- 18047931
TI  - Altered glycosylation of Tamm-Horsfall glycoprotein derived from renal allograft
      recipients leads to changes in its biological function.
AB  - BACKGROUND: Human urinary Tamm-Horsfall glycoprotein (THP) is a pleotropic
      protein that binds different cytokines and stimulates various immunocompetent
      cells. It is unclear whether these important functions of THP are altered in
      renal transplant patients. METHODS: We purified THPs from normal individuals (N
      THP) and renal transplant patients receiving potent immunosuppressants (R-THP).
      The carbohydrate (CHO) compositions of THPs were probed by lectin-blotting and
      lectin-binding ELISA. The functions of THP were assessed by immune cell
      stimulation as well as C1q, IL-1beta, IL-8 and TNF-alpha-binding assays. The
      roles of CHO moieties in THPs were analyzed using CHO-degrading enzyme digestion.
      RESULTS: Compared to that of N-THP, the binding capacity of R-THP to Maackia
      amurensis, Galanthus nivalis and Datura stamonium decreased, indicating that R
      THP contained lesser amount of Siaalpha(2,3)Gal/GalNAc, mannose residues, and
      beta(1,4)GlcNAc, but not GlcNAc/branched mannose. The binding capacity of R-THP
      to complement C1q and tumor necrosis factor (TNF)-alpha was also decreased. The
      stimulating effect of R-THP on mononuclear cell (MNC) proliferation and
      polymorphonuclear neutrophil (PMN) phagocytosis was less potent than that of N
      THP. We found that the defective MNC-stimulation by R-THP was due to impaired NF
      kappaB p52 nuclear translocation. The cell-stimulating effects of N- and R-THP
      could be abolished by digesting them with CHO-degrading enzymes, beta
      galactosidase and neuraminidase. Interestingly, a potent apoptosis-inducing
      effect of R-THP on MNC and PMN was noted. CONCLUSIONS: R-THP is not only modified
      in glycosylation but bears an apoptosis-inducing capacity on MNC and PMN, leading
      to an impaired immune function in renal transplant patients.

PMID- 18047932
TI  - CT60 A/G marker of the 3'-UTR of the CTLA4 gene and liver transplant.
AB  - The CTLA4 molecule is a homolog for CD28, and both molecules and their common
      ligands (CD80 and CD86) constitute the B7/CD28-CTLA4 co-stimulatory pathway for T
      cells activation. The CTLA4-ligand interaction has an inhibitory effect on T cell
      activation and might contribute to peripheral tolerance. A recently described
      CT60 A/G polymorphism affects the production of soluble CTLA4 and is strongly
      associated with immune-mediated diseases and with allogenic stem cell
      transplantation outcome. Thus, we examined this marker on liver transplant
      outcome by a PCR-RFLP method. The CT60 G allele was significantly associated with
      acute rejection (Pc=0.038; OR=1.49; AR vs. NAR). Patients who lacked this allele
      had the lowest risk of acute rejection development. Allograft survival data did
      not show statistical differences between genotypes. In conclusion, CT60 A/G
      dimorphism within the 3'-UTR of CTLA4 gene, which encodes for reduced sCTLA4
      production, influence acute rejection development in liver transplantation.

PMID- 18047933
TI  - FOXP3 mRNA expression analysis in the peripheral blood and allograft of heart
      transplant patients.
AB  - Previously, we demonstrated in heart transplant patients that FOXP3, a gene
      required for the development and function of regulatory T cells, was highly
      expressed in the graft during an acute cellular rejection. In this study, we
      analyzed whether the FOXP3 gene expression in the peripheral blood also reflects
      anti-donor immune responses, and therefore may provide clues for non-invasive
      detection of non-responsiveness or acute rejection. We examined the FOXP3
      expression patterns of peripheral blood mononuclear cells (PBMC; n=69) of 19
      heart transplant patients during quiescence and rejection in comparison with
      those of endomyocardial biopsies (EMB; n=75) of 24 heart transplant patients.
      While the FOXP3 mRNA levels were abundantly expressed in rejecting EMB (ISHLT
      rejection grade>1R) compared with EMB without histological evidence of myocardial
      damage (ISHLT rejection grade 0R-1R; p=0.003), no association with rejection or
      non-responsiveness was found for the FOXP3 mRNA levels in the peripheral blood.
      Thus, in contrast to intragraft FOXP3 gene expression, the peripheral FOXP3 mRNA
      levels lack correlation with anti-donor immune responses in the graft, and,
      consequently, FOXP3 does not appear to be a potential candidate gene for non
      invasive diagnosis of non-responsiveness or rejection.

PMID- 18047934
TI  - Diagnosis of renal allograft subclinical rejection by urine protein fingerprint
      analysis.
AB  - AIMS: This study aimed to find new biomarkers and establish urine protein
      fingerprint model for diagnosis of renal allograft subclinical rejection (SCR).
      METHODS: A total of 73 urine samples were analyzed by surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) combined
      with bioinformatics tools. RESULTS: Firstly, 22 urine samples from recipients of
      stable graft function proved by protocol biopsies and 27 from subclinical
      rejection gruop were analyzed by SELDI-TOF-MS and Zhejiang University Cancer
      Institute-ProteinChip Data Analysis System (ZUCI-PDAS). The diagnostic pattern
      comprised of 4 biomarkers could differentiate SCR group from stable group with
      sensitivity of 81.5% and specificity of 81.8%. The remaining 14 samples from
      stable group and 10 samples from SCR were analyzed on the second day as an
      independent test set. The independent tests yielded a specificity of 71.4% and
      sensitivity of 90%. CONCLUSIONS: Urine protein fingerprint analysis by SELDI-TOF
      MS combined with bioinformatics can help to discover new biomarkers and provide a
      non-invasive tool to diagnosis of SCR.

PMID- 18047935
TI  - Soluble CD30 levels as a diagnostic marker for bronchiolitis obliterans syndrome
      following human lung transplantation.
AB  - The long term survival of human lung allograft is hampered by the occurrence of
      chronic rejection, Bronchiolitis Obliterans Syndrome (BOS). This end-stage
      disease is normally diagnosed clinically by using the pulmonary function tests.
      This results in delay of BOS diagnosis and consequently prevents early
      intervention. It is generally accepted that alloimmunity plays an important role
      in chronic rejection of the allograft. In this study we analyzed serial serum
      samples from BOS+ and BOS- patients for sCD30 levels to determine the role of
      sCD30 to predict the onset of BOS. In contrast to BOS negative patients and
      normal subjects, 6 out of 9 BOS+ patients (p<0.05) studied had an increase in the
      sCD30 levels. Significantly, the rise was noted 7.57+/-2.63 months before the
      clinical diagnosis was evident. Therefore, we propose that the rise in serum
      sCD30 levels can be used as a marker for the detection of patients who are at
      risk of development of BOS.

PMID- 18047936
TI  - Increased vascular endothelial growth factor mRNA in endomyocardial biopsies from
      allografts demonstrating severe acute rejection: a longitudinal study.
AB  - Investigation into the contribution of the immune system and inflammatory cascade
      to acute rejection (AR) and cardiac allograft vasculopathy (CAV) has implicated
      vascular endothelial growth factor (VEGF). The endomyocardial biopsy (EB) has
      proved invaluable in the diagnosis of AR, and in providing information concerning
      the biological processes occurring following transplantation. The association
      between VEGF and AR and the development of CAV was examined in endomyocardial
      biopsies (EBs) from a cohort of 76 heart transplant recipients. VEGF mRNA levels
      were quantified through real time RT-PCR in 712 EBs, obtained at routine
      intervals during post-operative monitoring. VEGF and leukocyte and endothelial
      markers were assessed in a subset of biopsies through immunohistochemistry. The
      results of generalised linear modelling, adjusting for covariates, revealed VEGF
      mRNA expression was 19% greater during severe AR as compared to no rejection
      (p=0.007). Immunohistochemical results supported these findings. Mean VEGF mRNA
      levels were not significant predictors for the development of CAV (p=0.554).
      However the risk of cardiac related death increased 9-fold for a 1 unit increase
      in mean VEGF expression (p=0.006). Similarly, a single unit increase in mean AR
      severity equated to a 10-fold increase in the risk of cardiac related death
      (p<0.005). Our data suggest that increased VEGF expression is strongly associated
      with severe AR and cardiac related death.

PMID- 18047937
TI  - Chemokine redundancy in BOS pathogenesis. A possible role also for the CC
      chemokines: MIP3-beta, MIP3-alpha, MDC and their specific receptors.
AB  - Bronchiolitis obliterans syndrome (BOS) is one of the most important factors
      limiting the long-term survival of lung transplant recipients (LTR), however its
      pathogenesis still remains unclear. We hypothesized that an increased production
      of certain specific proinflammatory mediators in the first post-transplant year
      would predispose to BOS. We retrospectively evaluated temporal kinetics of some
      CC chemokines that have not yet been evaluated, including CCL3/MIP1-alpha,
      CCL4/MIP1-beta, CCL17/TARC, CCL19/MIP3-beta, CCL20/MIP3-alpha, CCL22/MDC and
      CCL26/eotaxin, in broncho-alveolar lavage fluid (BAL-f) in the first post
      transplant year in a cohort of 8 LTR before the development of BOS (pre-BOS LTR)
      and 8 LTR with long-term stable clinical conditions (stable LTR). Chemokine
      levels were assayed by means of a multiplex sandwich ELISA. Furthermore, for
      those ligands which resulted significantly predictive of BOS onset, we analyzed
      the expression of specific receptors (CCR) on BAL cells. The proportion of CCR
      expressing BAL cells was assessed by flow cytometry. We demonstrated that MIP3
      beta/CCL19, MIP3-alpha/CCL20, MDC/CCL22 levels at 6 months post-transplant
      significantly predicted BOS onset. In addition, the temporal behavior of these
      factors resulted significantly different in pre-BOS patients as compared to
      stable LTR. Finally the expression of CCR was documented on BAL lymphocytes and
      macrophages, and, in some cases, their expression was found to vary between the
      two groups. Within the complexity of the chemokine network, these three CCL
      factors could play an additive role in the pathogenesis of the inflammatory
      process leading to bronchiolar fibro-obliteration.

PMID- 18047938
TI  - Comparison of single bolus ATG and Basiliximab as induction therapy in
      presensitized renal allograft recipients receiving tacrolimus-based
      immunosuppressive regimen.
AB  - Presensitized renal allograft recipients require special management to improve
      their outcome, and there is no consensus on the optimal immunosuppressive
      strategy. We retrospectively analyzed clinical data of 82 patients, who were PRA
      positive pre-transplant (above 10%) and received single bolus ATG and basiliximab
      as induction therapy, and assessed safety and efficacy of two kinds of induction
      therapies. Patients of ATG group (n=40) received single bolus ATG (Fresenius, 9
      mg/kg preoperatively) and those of basiliximab group (n=42) were given two doses
      of basiliximab (Simulect, Novartis, 20 mg) on days 0 and 4 post-transplant. All
      patients received standard triple immunosuppressive therapy with tacrolimus (FK
      506), mycophenolate mofetil (MMF), and steroids. The follow-up time was 12
      months. There was no hyperacute rejection in two groups, and delayed graft
      function occurred in two patients of ATG group and three of basiliximab group.
      After 12-month follow-up, more acute rejection (AR) episodes were observed in
      basiliximab group than ATG group (35.7% vs. 15%, P=0.032). Although highly
      significant differences were observed between ATG group and basiliximab group
      with respect to the incidence of thrombocytopenia (P=0.001), single bolus ATG was
      well tolerated. Incidences of other adverse events and infection episodes did not
      differ between two groups (P>0.05). One-year patient and graft survival was 95%,
      92.5% and 95.2%, 88.1% in ATG and basiliximab group respectively (P>0.05). Both
      single bolus ATG and basiliximab induction therapy achieved similar one-year
      graft/patient survival. However, single bolus ATG yielded much lower AR rate than
      basiliximab without increase in infection episodes and severe adverse events.

PMID- 18047939
TI  - HLA-Cw allele frequencies in northern and southern Italy.
AB  - The evidence for HLA-Cw antigens' involvement in the modulation of the immune
      response in bone marrow transplantation, NK alloreactivity and the susceptibility
      and follow-up for different diseases has been growing in the recent years, but
      very few data on HLA-Cw distribution in healthy Italian subjects are available to
      date. This report presents an updated description of HLA-Cw frequencies in Italy,
      comparing data from the northern (Lombardia) and southern (Campania and Puglia)
      parts of the country. A total of 1101 healthy subjects of Italian origin were
      genotyped, and the results showed that HLA-Cw*04, Cw*07, Cw*12, and, in
      particular, Cw*0401, Cw*0701, Cw*1203, were the most frequent alleles found in
      all three regions analysed. Nevertheless, statistically significant differences
      were observed in Cw*07 distribution, which was more frequent in the southern than
      in the northern part of Italy (28.8% vs 22.4%; p=0.001; OR: 1.4; 95%CI: 1.14
      1.73), and in Cw*12 distribution, which was more frequent in the north than the
      south (17.0% vs 12.4%; p=0.007, OR: 1.4; 95%CI: 1.10-1.91). These results, which
      give an improved pattern of distribution of HLA-Cw alleles in the Italian
      population, would be useful in bone marrow transplantation and anthropological
      studies. Moreover, due to the important role of HLA-Cw antigens in modulation of
      the immune response and NK alloreactivity, these data would be of interest in
      studies on susceptibility, follow-up and/or protection against different
      diseases.

PMID- 18047940
TI  - Electronic media, violence, and adolescents: an emerging public health problem.
AB  - Adolescents' access to and use of new media technology (e.g., cell phone,
      personal data assistant, computer for Internet access) are on the rise, and this
      explosion of technology brings with it potential benefits and risks. Attention is
      growing about the risk of adolescents to become victims of aggression perpetrated
      by peers with new technology. In September 2006, the Centers for Disease Control
      and Prevention convened a panel of experts in technology and youth aggression to
      examine this specific risk. This special issue of the Journal of Adolescent
      Health presents the data and recommendations for future directions discussed at
      the meeting. The articles in the Journal support the argument that electronic
      aggression is an emerging public health problem in need of additional prevalence
      and etiological research to support the development and evaluation of effective
      prevention programs.

PMID- 18047941
TI  - Prevalence and predictors of internet bullying.
AB  - PURPOSE: With the Internet quickly becoming a new arena for social interaction,
      it has also become a growing venue for bullying among youth. The purpose of the
      present study was to contrast the prevalence of Internet bullying with physical
      and verbal bullying among elementary, middle, and high school boys and girls, and
      to examine whether key predictors of physical and verbal bullying also predicted
      Internet bullying. METHODS: As part of an ongoing, statewide bullying prevention
      initiative in Colorado, 3,339 youth in Grades 5, 8, and 11 completed
      questionnaires in 78 school sites during the fall of 2005, and another 2,293
      youth in that original sample participated in a follow-up survey in 65 school
      sites in the spring of 2006. Questionnaires included measures of bullying
      perpetration and victimization, normative beliefs about bullying, perceptions of
      peer social support, and perceptions of school climate. RESULTS: The highest
      prevalence rates were found for verbal, followed by physical, and then by
      Internet bullying. Physical and Internet bullying peaked in middle school and
      declined in high school. Verbal bullying peaked in middle school and remained
      relatively high during high school. Males were more likely to report physical
      bullying than females, but no gender differences were found for Internet and
      verbal bullying. All three types of bullying were significantly related to
      normative beliefs approving of bullying, negative school climate, and negative
      peer support. CONCLUSIONS: Preventive interventions that target school bullying
      by changing norms about bullying and school context may also impact Internet
      bullying, given the shared predictors.

PMID- 18047942
TI  - Electronic bullying among middle school students.
AB  - PURPOSE: Electronic communications technologies are affording children and
      adolescents new means of bullying one another. Referred to as electronic
      bullying, cyberbullying, or online social cruelty, this phenomenon includes
      bullying through e-mail, instant messaging, in a chat room, on a website, or
      through digital messages or images sent to a cell phone. The present study
      examined the prevalence of electronic bullying among middle school students.
      METHODS: A total of 3,767 middle school students in grades 6, 7, and 8 who attend
      six elementary and middle schools in the southeastern and northwestern United
      States completed a questionnaire, consisting of the Olweus Bully/Victim
      Questionnaire and 23 questions developed for this study that examined
      participants' experiences with electronic bullying, as both victims and
      perpetrators. RESULTS: Of the students, 11% that they had been electronically
      bullied at least once in the last couple of months (victims only); 7% indicated
      that they were bully/victims; and 4% had electronically bullied someone else at
      least once in the previous couple of months (bullies only). The most common
      methods for electronic bullying (as reported by both victims and perpetrators)
      involved the use of instant messaging, chat rooms, and e-mail. Importantly, close
      to half of the electronic bully victims reported not knowing the perpetrator's
      identity. CONCLUSIONS: Electronic bullying represents a problem of significant
      magnitude. As children's use of electronic communications technologies is
      unlikely to wane in coming years, continued attention to electronic bullying is
      critical. Implications of these findings for youth, parents, and educators are
      discussed.

PMID- 18047943
TI  - The co-occurrence of Internet harassment and unwanted sexual solicitation
      victimization and perpetration: associations with psychosocial indicators.
AB  - PURPOSE: Previous research in offline environments suggests that there may be an
      overlap in bullying and sexual harassment perpetration and victimization; however
      to what extent this may be true for perpetration and victimization of Internet
      harassment and unwanted sexual solicitation is unknown. METHODS: The Growing Up
      with Media survey is a national cross-sectional online survey of 1,588 youth, 10
      15 years old, who have used the Internet at least once in the last 6 months.
      Cluster analysis was conducted with four scales: Internet harassment
      perpetration, Internet harassment victimization, unwanted sexual solicitation
      perpetration, and unwanted sexual solicitation victimization. RESULTS: A four
      cluster solution was identified: youth with little to no involvement (n = 1326;
      81.7%); perpetrator-victims of Internet harassment (n = 205; 14.3%); victims of
      both Internet harassment and unwanted sexual solicitation (n = 45; 3.1%); and
      perpetrator-victims of Internet harassment and unwanted sexual solicitation (n =
      12; .9%). Involvement in Internet harassment and unwanted sexual solicitation was
      associated with concurrent reports of psychosocial problems including substance
      use; involvement in offline victimization and perpetration of relational,
      physical, and sexual aggression; delinquent peers; a propensity to respond to
      stimuli with anger; poor emotional bond with caregivers; and poor caregiver
      monitoring as compared with youth with little to no involvement. This was
      especially true for perpetrator-victims of Internet harassment and unwanted
      sexual solicitation. Findings were replicated using a frequency-based definition
      of involvement, suggesting that cluster analysis is useful in identifying
      subgroups of youth and can be used to guide frequency-based definitions, which
      are easier to implement across study samples. CONCLUSIONS: The majority of youth
      are not frequently involved in Internet harassment or unwanted sexual
      solicitation either as victims or as perpetrators. Among those who are, however,
      psychosocial problems are apparent. Perpetrator-victims of Internet harassment
      and unwanted sexual solicitation have emerged as a particularly important group
      for adolescent health professionals to be aware of, identify, and treat or refer
      into services immediately.

PMID- 18047944
TI  - Examining the overlap in internet harassment and school bullying: implications
      for school intervention.
AB  - PURPOSE: As more and more youth utilize the Internet, concern about Internet
      harassment and its consequences for adolescents is growing. This paper examines
      the potential overlap in online and school harassment, as well as the concurrence
      of Internet harassment and school behavior problems. METHODS: The Growing Up with
      Media survey is a national cross-sectional online survey of 1588 youth between
      the ages of 10 and 15 years old. Our main measures were Internet harassment
      (i.e., rude or nasty comments, spreading of rumors, threatening or aggressive
      comments) and school functioning (i.e., academic performance; skipping school;
      detentions and suspensions; and carrying a weapon to school in the last 30 days).
      RESULTS: Although some overlap existed, 64% of youth who were harassed online did
      not report also being bullied at school. Nonetheless, youth harassed online were
      significantly more likely to also report two or more detentions or suspensions,
      and skipping school in the previous year. Especially concerning, youth who
      reported being targeted by Internet harassment were eight times more likely than
      all other youth to concurrently report carrying a weapon to school in the past 30
      days (odds ratio = 8.0, p = .002). CONCLUSIONS: Although the data do not support
      the assumption that many youth who are harassed online are bullied by the same
      (or even different) peers at school, findings support the need for professionals
      working with children and adolescents, especially those working in the schools,
      to be aware of the possible linkages between school behavior and online
      harassment for some youth.

PMID- 18047945
TI  - Does online harassment constitute bullying? An exploration of online harassment
      by known peers and online-only contacts.
AB  - PURPOSE: To shed light on the nature of online harassment and the extent to which
      it may be bullying by examining differences in the characteristics of harassed
      youth, online harassment incidents, and distressing online harassment based on
      the identity of online harassers (known peer vs. online-only contact). METHODS: A
      telephone survey of a nationally representative sample of 1500 youth Internet
      users, ages 10 to 17, conducted between March and June 2005. RESULTS: Nine
      percent (n = 129) of youth were harassed online in the past year, 43% (n = 56) by
      known peers and 57% (n = 73) by people they met online and did not know in person
      (online-only contacts). Most online harassment incidents did not appear to meet
      the standard definition of bullying used in school-based research and requiring
      aggression, repetition, and power imbalance. Only 25% of incidents by known peers
      and 21% by online-only contacts involved both repeated incidents and either
      distress to targets or adult intervention. CONCLUSIONS: In many cases, the
      concept of "bullying" or "cyber-bullying" may be inappropriate for online
      interpersonal offenses. We suggest using "online harassment," with disclaimers
      that it does not constitute bullying unless it is part of or related to offline
      bullying. This would include incidents perpetrated by peers that occur entirely
      online, but arise from school-related events or relationships and have school
      related consequences for targets. The Internet provides opportunities for the
      extension of conventional school bullying to new venues. Those who study
      conventional school bullying should include online forms of the behavior in
      research, prevention, and intervention paradigms.

PMID- 18047946
TI  - Students' perspectives on cyber bullying.
AB  - The aim of this study was to gain a better understanding of the impact of cyber
      bullying on students and the possible need for prevention messages targeting
      students, educators, and parents. A total of 148 middle and high school students
      were interviewed during focus groups held at two middle and two high schools in a
      public school district. The focus groups were approximately 45 minutes in length.
      Students were divided by gender and asked a series of scripted questions by a
      same-gender student assistance counselor. We found that students' comments during
      the focus groups suggest that students-particularly females-view cyber bullying
      as a problem, but one rarely discussed at school, and that students do not see
      the school district personnel as helpful resources when dealing with cyber
      bullying. Students are currently experiencing the majority of cyber bullying
      instances outside of the school day; however there is some impact at school.
      Students were able to suggest some basic strategies for dealing with cyber
      bullying, but were less likely to be aware of strategies to request the removal
      of objectionable websites, as well as how to respond as a helpful bystander when
      witnessing cruel online behavior. We conclude that school districts should
      address cyber bullying through a combination of policies and information that are
      shared with students and parents. Schools should include cyber bullying as part
      of their bullying prevention strategies and include classroom lessons that
      address reporting and bystander behavior.

PMID- 18047947
TI  - The impact of electronic media violence: scientific theory and research.
AB  - Since the early 1960s, research evidence has been accumulating that suggests that
      exposure to violence in television, movies, video games, cell phones, and on the
      Internet increases the risk of violent behavior on the viewer's part, just as
      growing up in an environment filled with real violence increases the risk of them
      behaving violently. In the current review this research evidence is critically
      assessed and the psychological theory that explains why exposure to violence has
      detrimental effects for both the short and long-term is elaborated. Finally the
      size of the "media violence effect" is compared with some other well-known
      threats to society to estimate how important a threat it should be considered.

PMID- 18047948
TI  - Education policy implications from the Expert Panel on Electronic Media and Youth
      Violence.
AB  - The research from the Expert Panel on Electronic Media and Youth Violence makes a
      compelling case for why educators and education policymakers should care about
      the effects of media on youth behavior, and the growing phenomenon of Internet
      bullying and harassment. The ability of the U.S. education system to respond is
      limited not only by competing instructional priorities but also by the governance
      structure of the education system itself. The federal role is limited to a
      proportionally small amount of funding for states and schools, to raising public
      awareness, and to providing research and data. States can set priorities, make
      requirements, and direct funding. Districts and schools ultimately have the most
      control over prevention program selection and setting social and behavioral
      norms. Key implications of the panel's research for educators and education
      policymakers include: Internet bullying is correlated with school behavior
      problems; Internet bullying behavior may peak in middle school; Internet bullying
      shares common predictors with verbal and, to some extent, physical bullying;
      Media literacy programs may mitigate the negative effects of electronic media on
      youth. Specific recommendations based on these conclusions are discussed, and
      research priorities for the prevention and education fields are identified.

PMID- 18047950
TI  - Surf and turf wars online--growing implications of Internet gang violence.
AB  - To examine use of the Internet by gangs and its affect on youth, i-SAFE Inc.
      collected information from more than 100,000 students and 137 gang associates
      from an urban population. Although individuals who associate with a gang have
      distinguishable discrepancies in the amount of time spent online, they have
      similar online behavior as compared with those who are not involved with gangs.
      Additional research is necessary to develop a substantive link between gangs
      online and the school and community culture.

PMID- 18047949
TI  - The authority and responsibility of school officials in responding to
      cyberbullying.
AB  - Online social aggression, or cyberbullying, involves speech. Many incidents
      involve off-campus online speech that either creates or has the potential to
      create disruption at school or that may interfere with the targeted student's
      ability to participate in educational activities and programs. Addressing these
      situations requires an assessment of the extent of authority and responsibility
      of school officials to respond. "Authority" refers to the legally justified right
      to impose formal discipline. Because cyberbullying involves online speech, the
      question of legal authority necessarily involves addressing the balance between
      the student right of free speech and student safety and security.
      "Responsibility" refers to the legal obligation under negligence theory and civil
      rights laws to exercise reasonable precautions to protect students from online
      social aggression and to intervene in response to reports of actual incidents.

PMID- 18047951
TI  - Vaccine therapy for prostate cancer.
AB  - Immunotherapy with vaccines represents a novel, targeted nontoxic modality for
      the therapy of prostate cancer. Systemic immune responses to candidate prostate
      cancer antigens have been induced in a tumor that has been conventionally viewed
      as refractory to immunotherapy. Autologous dendritic cell vaccines expressing
      prostate-specific antigens have shown promising clinical outcomes in a randomized
      trial in metastatic androgen independent prostate cancer. Other vaccine
      approaches include granulocyte-macrophage colony-stimulating factor modified
      tumor cell vaccines and poxvirus vaccines. A combination of vaccines with
      chemotherapy, radiotherapy, and other biologic agents is also being evaluated.
      Efforts to optimize vaccine approaches and select ideal patient populations need
      to continue because there is no evidence supporting a single superior approach.

PMID- 18047952
TI  - Evaluation of the prostate peripheral zone/capsule in patients undergoing radical
      cystoprostatectomy: defining risk with prostate capsule sparing cystectomy.
AB  - OBJECTIVES: Prostate capsule sparing cystectomy has been performed in conjunction
      with orthotopic diversion to preserve sexual function and improve urinary
      control. Because concerns remain regarding incomplete surgical resection, we
      evaluated the risk of urothelial and prostate cancer in a series of patients
      undergoing radical cystoprostatectomy. METHODS: A total of 35 men undergoing
      radical cystoprostatectomy (August 2003-August 2005) had separate submission of
      the prostate peripheral zone/capsule from the prostate adenoma and bladder after
      surgery. These specimens were evaluated for bladder and prostate cancer grade,
      stage, and largest diameter of prostate cancer. Patient records were reviewed for
      demographic and medical information. Clinical variables were compared between
      patients with and without carcinoma involving the prostate using standard
      statistical software. RESULTS: Of patients, 57% had cancer involving the prostate
      at radical cystoprostatectomy. There were 9 patients (26%) who had urothelial
      carcinoma involving the prostate; only prostatic urethral biopsy identified these
      patients before radical cystoprostatectomy. Prostate adenocarcinoma was evident
      in 16 of 35 (47%) patients, with a majority involving the prostate peripheral
      zone/capsule (43%). There were 4 patients (11%) who had clinically significant
      prostate cancer (Gleason sum >6 or tumor volume >0.5 cm(3)). Patients with
      prostate cancer were significantly older than patients without prostate cancer (P
      = 0.01). CONCLUSIONS: No clinical variable can confidently predict patients with
      prostate cancer involving the prostate. Because a majority of patients undergoing
      radical cystoprostatectomy have cancer involving their prostate, preoperative
      evaluation with prostatic urethral and prostate biopsy may be useful to guide
      patient selection for prostate capsule sparing cystectomy.

PMID- 18047953
TI  - Is a cystogram necessary after robot-assisted radical prostatectomy?
AB  - PURPOSE: Robot-assisted radical prostatectomy has become an acceptable option for
      the treatment of clinically localized prostate cancer. The role of cystography in
      robot-assisted radical prostatectomy was evaluated prospectively. METHODS AND
      MATERIALS: A total of 80 consecutive patients who underwent robot-assisted
      radical prostatectomy with an intraperitoneal approach were evaluated. There were
      40 patients (group 1/surgeon A) who received a routine postoperative cystogram
      before Foley catheter removal. An additional 40 patients (group 2/surgeon B) had
      their catheters removed without radiographic imaging. Patient demographics,
      intraoperative data, postoperative data, and complications were recorded
      prospectively. RESULTS: The 2 groups were similar in age, Gleason score, and
      history of previous urethral/bladder neck surgery. Univariate analysis showed no
      statistical difference among case duration, estimated blood loss, need for
      bladder neck reconstruction, presence of visible anastomotic leak, or use of
      pelvic drains. Anastomosis time was the only variable that reached statistical
      significance. Mean catheter duration (11 days) was similar between the 2 groups.
      There were 3 patients from group 1 who had an anastomotic leak identified on a
      cystogram. In group 2, 1 patient had a persistent mild leak based on a cystogram
      obtained for urinary symptoms. No patient in either group had urinary retention,
      urinary tract infection, renal failure, or bladder neck contracture develop. The
      degree of postoperative urinary incontinence was similar between groups.
      CONCLUSION: Foley catheter removal on postoperative days 8-10 after robot
      assisted radical prostatectomy without routine cystography appears safe.

PMID- 18047954
TI  - Association of cyclin D1 and E1 expression with disease progression and
      biomarkers in patients with nonmuscle-invasive urothelial cell carcinoma of the
      bladder.
AB  - PURPOSE: To determine the association of cyclin D1 and E1 expression with bladder
      cancer presence, clinical and molecular characteristics, and disease progression
      in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder.
      METHODS: Immunohistochemical staining for cyclin D1, cyclin E1, p53, p21, p27,
      pRB, KI-67, and survivin was performed on a tissue microarray containing
      specimens from 9 normal controls and 74 patients with Ta, Tis, and/or T1
      urothelial cell carcinoma of the bladder. Cyclin D1 and E1 immunoreactivity were
      considered low when samples showed less than 10% and 30% nuclear reactivity,
      respectively. RESULTS: Normal bladder urothelium from all 9 control patients
      showed uniformly intense expression of cyclin D1 and cyclin E1. Cyclin D1 and E1
      expression were low in 23 of 74 (31.1%) and 27 of 74 (36.5%) specimens. Kaplan
      Meier analyses showed that low expression of cyclin E1 was significantly
      associated with an increased probability of tumor recurrence and progression in
      univariate, but not multivariate analysis. Cyclin D1 immunoreactivity was not
      associated with any pathologic characteristics or clinical outcomes. Low cyclin
      E1 expression was significantly associated with altered expression of p53, pRB,
      KI-67, and survivin. CONCLUSIONS: Tissue expression of cyclin D1 or E1 seems not
      to add independent prognostic value to standard features in patients with
      nonmuscle -invasive urothelial cell carcinoma of the bladder.

PMID- 18047955
TI  - Optimizing chemotherapy for transitional cell carcinoma by application of bcl-2
      and bcl-xL antisense oligodeoxynucleotides.
AB  - OBJECTIVE: Therapy failure after intravesical and systemic chemotherapy for
      transitional cell carcinoma (TCC) is still high. Antiapoptotic proteins such as
      Bcl-2 and Bcl-xL have been reported to promote chemoresistance in TCC. Targeting
      bcl-2 and bcl-xL messenger ribonucleic acid with antisense oligodeoxynucleotides
      (AS-ODNs) may enhance the cytotoxic effects of chemotherapeutic agents.
      Therefore, we investigated the effects of bcl-2 and bcl-xL AS-ODNs in combined
      treatment with conventional and new chemotherapeutic agents to evaluate the
      cytotoxic effects in comparison to monotreatment. METHODS AND MATERIALS: Western
      blot analysis or immunohistochemistry verified Bcl-2 and Bcl-xL expression in a
      panel of human TCC cell lines that had been monotreated with cisplatin,
      gemcitabine, mitomycin C, and paclitaxel. In addition, bcl-2 or bcl-xL AS-ODNs
      were applied in combination with each chemotherapeutic agent. Cell viability was
      determined using a standard MTT assay and Neubauer hemocytometry. RESULTS: All
      cell lines responded to chemotherapeutic monotreatment in a dose-dependent
      manner. Maximum cell death rates after monotreatment were 47.4% (cisplatin),
      39.0% (gemcitabine), 83.4% (mitomycin C), and 54.8% (paclitaxel). After combined
      treatment with chemotherapy and bcl-2 or bcl-xL AS-ODNs, cell death rates were
      significantly higher (e.g., 30.3% vs. 87.2% in HT 1197 cells for monotreatment
      vs. the combination of paclitaxel and bcl-xL AS-ODNs). Three-way analysis of
      variance revealed that combined treatment had a significant effect on all cell
      lines. CONCLUSIONS: Our study confirms that the addition of bcl-2 and bcl-xL AS
      ODNs enhances the cytotoxic potential of chemotherapeutic agents in TCC cell
      lines as a result of combined effects. Further trials in ex vivo and in vivo
      models have to be performed to promote clinical application in patients.

PMID- 18047958
TI  - Debate: Open radical prostatectomy vs. laparoscopic vs. robotic.
AB  - Surgical removal of clinically localized prostate cancer remains the most
      definitive treatment for the disease. The emergence of laparoscopic and robotic
      radical prostatectomy (RP) as alternatives to open RP has generated considerable
      discussion about the real and relative merits of each approach. Such was the
      topic of a debate that took place during the 2006 Society of Urologic Oncology
      meeting. The participants were Dr. William Catalona, Northwestern University,
      advocating for open RP, Dr. Betrand Guillonneau, Memorial Sloan Kettering Cancer
      Center advocating for laparoscopic RP, and Dr. Mani Menon, Henry Ford Hospital,
      advocating for robotic RP. The debate was moderated by Dr. Joel Nelson,
      University of Pittsburgh. This paper summarizes that debate.

PMID- 18047956
TI  - Doxazosin-induced clusterin expression and apoptosis in prostate cancer cells.
AB  - The purpose of this study was to correlate temporal expression of clusterin and
      apoptosis in androgen-independent human prostate cancer cells (PC-3) treated with
      25 microM doxazosin. DNA fragmentation, reverse transcriptase polymerase chain
      reaction, and terminal transferase-mediated biotinylated 16-desoxy-uridene
      triphosphate nick-end labeling (TUNEL) assays were used to assess degree of
      apoptosis and temporal and spatial expression of clusterin mRNA and protein. DNA
      fragmentation was significant at 48 hours. Clusterin mRNA expression was 3-fold
      higher than control at 9 hours and was maintained over 48 hours. The TUNEL assay
      showed increasing percentage of apoptotic cells and presence of clusterin after
      doxazosin treatment. During doxazosin-induced apoptosis in PC3 cells, clusterin
      appeared to initially accumulate in the cytoplasm and protect against apoptosis;
      later, after its transport to the nucleus, clusterin was no longer able to
      suppress apoptosis.

PMID- 18047959
TI  - Open radical retropubic prostatectomy.
AB  - For more than two decades, open radical prostatectomy has been considered the
      gold standard for the surgical management of prostate cancer. More recently,
      however, laparoscopic and now robotic approaches to radical prostatectomy have
      become increasingly popular. It is unclear whether these techniques are
      associated with any material advantage with regard to short-term convalescence.
      In addition, the high positive surgical margin rates reported with robotic
      prostatectomy are concerning, particularly early in the learning curve.
      Additional experience with these methods and long-term follow-up data are
      necessary to determine whether the cancer control and functional outcomes meet
      the standards of open radical prostatectomy.

PMID- 18047960
TI  - Laparoscopic radical prostatectomy: contemporary comparison with open surgery.
AB  - INTRODUCTION: The optimal outcome of radical prostatectomy is to cure cancer with
      the least impact on quality of life. The aim of this paper is to review the
      existent literature and attempt to compare the results of the retropubic (RRP)
      with the laparoscopic (LRP) approach. METHODOLOGY: Extensive Medline literature
      search for terms "radical retropubic prostatectomy" and "laparoscopic radical
      prostatectomy" from 1980 to 2006 to compare cancer control, functional outcomes
      and morbidity for both groups. Only full length English language articles
      including 100 or more patients were considered. RESULTS: The 5-year biochemical
      recurrence rates range from 70-92% for the RRP vs. 82-91% for the LRP. The global
      positive surgical margin rates are 12-20% for the RRP and 17-30% for the LRP. The
      continence rate for the RRP varies from 70-93%; the LRP varies from 82-95% for 12
      months. Considering potency 12 months after surgery, the rates are 17-75% for the
      RRP vs. 52-78% for the LRP. The blood loss for the RRP ranges from 818 to 1,500
      ml and 220 to 1,100 for the LRP. CONCLUSIONS: The concurrent literature lacks
      randomized trials comparing the different surgical techniques. No definitive
      conclusions can be drawn.

PMID- 18047961
TI  - Active surveillance for favorable risk prostate cancer: rationale, risks, and
      results.
AB  - Active surveillance for favorable risk prostate cancer has become increasingly
      popular in populations where prostate cancer screening is widespread, due to
      evidence that prostate cancer screening results in the detection of disease that
      is not clinically significant in many patients (i.e., untreated, would not pose a
      threat to health). This approach is supported by data demonstrating that patients
      who fall into the category of clinically insignificant disease can be identified
      with reasonable accuracy, and that patients who are initially classified as low
      risk who reclassify over time as higher risk and are then treated more
      aggressively are in most cases still cured. An active surveillance approach means
      (1) identifying patients who have a low likelihood of disease progression during
      their lifetime, based on clinical and pathologic features of the disease and
      patient age and comorbidity; (2) monitoring closely over time, (3) establishing
      reasonable criteria for intervention, which will both identify more aggressive
      disease in a timely fashion, and not result in excessive treatment, and (4)
      meeting the communication challenge to reduce the psychological burden of living
      with untreated cancer. The results of active surveillance, the criteria for
      patient selection, and the appropriate triggers for intervention are reviewed.

PMID- 18047962
TI  - Low risk prostate cancer in men under age 65: the case for definitive treatment.
AB  - The management of low risk prostate cancer, defined as Gleason's sum <or=6, PSA
      <10 ng/ml, and clinical stage T1c to T2a, remains controversial. There is
      substantiating evidence to suggest that a subset of early stage, low risk cancers
      can cause significant patient morbidity and death in the long term. Studies have
      shown that the natural history of untreated prostate cancer is to progress,
      particularly after 15 years of followup. The majority of men seeking definitive
      surgical treatment in contemporary series fall within 55 to 65 years of age and
      are expected to enjoy an overall life expectancy ranging from about 15 to 30
      years, placing these men at long-term risk for disease progression and prostate
      cancer-specific death if managed expectantly. During the past 2 decades,
      refinements in surgical technique and in the delivery of external beam radiation
      have resulted in excellent long-term cancer control and favorable quality of life
      outcomes following treatment. Active surveillance with selective delayed
      intervention assumes that an individual's cancer will not progress outside the
      window of curability during the surveillance period, that markers for disease
      progression are reliable, and that patients are compliant. Until we understand
      better the long-term natural history of untreated prostate cancer, have more
      reliable and accurate markers to detect disease progression with certainty, and
      can risk stratify more precisely the subgroup of men with low risk cancers who
      will eventually succumb to their disease, early definitive therapy seems prudent.

PMID- 18047963
TI  - Adjuvant radiotherapy for high-risk patients following radical prostatectomy.
AB  - It is well recognized that radiation can eradicate microscopic neoplastic
      disease. For that reason it is considered standard treatment in most cancers to
      give post operative radiation not only for patients with microscopically positive
      margins, but also for other high risk patients. In spite of the widespread use of
      adjuvant radiotherapy in other cancers, adjuvant post operative radiation has not
      been routinely or uniformly used in patients after prostatectomy. The reasons for
      this have included the following: 1) Not all patients with positive margins will
      fail; 2) A biomarker prostate specific antigen (PSA) exists that can help predict
      the patient who is at-risk prior to evidence of clinical recurrence; 3) Some
      tumors that fail locally are biologically aggressive and will invariably fail
      systemically; 4) There is no assurance that radiation consistently eradicates
      local disease; 5) Even if local disease is eradicated, distant progression may
      not be effected; and 6) Potential toxicity may outweigh benefit of adjuvant
      therapy. These issues have been debated for over 3 decades, but it appears that
      data are now available to address these questions.

PMID- 18047964
TI  - Update on partial nephrectomy and novel techniques.
AB  - The treatment of renal tumors with the technique of partial nephrectomy continues
      to evolve. The relevant literature reviewed confirmed the excellent oncological
      outcomes associated with partial nephrectomy in properly selected patients. In
      addition, much data is being accumulated regarding the safety and efficacy of
      this technique via a laparoscopic approach. With either approach, the chance for
      renal preservation would appear to be a major benefit while "non-hilar" clamping
      techniques during the open approach may maximize the likelihood for maintenance
      of long-term renal function.

PMID- 18047965
TI  - The best treatment for high-grade T1 bladder cancer is cystectomy.
AB  - OBJECTIVES: To evaluate the role of initial cystectomy in the management of high
      grade T1 bladder cancer. METHODS: A selected review of the literature was
      performed to evaluate outcomes with intravesical therapy vs. initial cystectomy
      in this patient population, with a focus on identifying risk factors for failure
      of conservative therapy. RESULTS: Many studies in the literature fail to include
      central pathologic review and re-TUR clinical staging, and there are no
      randomized studies comparing outcomes with these two initial approaches.
      Retrospective studies of patients with high-grade T1 tumors treated with initial
      intravesical therapy suggest that approximately 30% of patients will ultimately
      require cystectomy, and 30% will die of their disease with or without cystectomy.
      The risk of progression continues for the life of the patient, and late
      recurrence and progression is common. Initial clinical and pathologic factors can
      be identified that predict a high risk of progression and are reasonable
      indicators for initial cystectomy. CONCLUSION: Radical cystectomy can provide a
      very high cure rate for these patients and should be considered early in the
      treatment plan.

PMID- 18047975
TI  - Hallmarking forty years of legislative history.

PMID- 18047976
TI  - Same old, same old.

PMID- 18047977
TI  - Voice recognition technology for radiology reporting: transforming the
      radiologist's value proposition.

PMID- 18047978
TI  - The myth of Sisyphus.

PMID- 18047979
TI  - Last exit: the Clinton health care plan revisited.

PMID- 18047980
TI  - What to know about the warranties on your medical equipment.

PMID- 18047981
TI  - 2007 ACR presidential oration: four foundations for our future.
AB  - In this 2007 Presidential Address, James P. Borgstede, MD, makes 4 requests of
      radiologists. These requests are first, that they be adaptive to change. Second,
      that they uphold quality medical imaging as a part of a specialty rather than a
      commodity. Third, that they develop a pay-it-forward sense of responsibility. And
      fourth, that they embrace the perspective of patient primacy. He opines that the
      future of radiology lies in an evolution to a specialty with greater emphasis on
      functional imaging and with physiologic orientation. He states that radiology and
      the ACR cannot be the organization seeking legislative protection for exclusivity
      of imaging services based on specialty title, but instead must be the specialty
      seeking public protection based on radiologists' ability to provide services with
      quality. He further states that radiology is commoditized through the
      inappropriate use of imaging requests as orders for tests rather than requests
      for consultations and by inappropriate use of digital imaging and electronic
      transfer of data. In addition, if radiologists keep patient primacy first in all
      of their considerations, they will ultimately do what is best for radiology as a
      specialty as well.

PMID- 18047982
TI  - 2007 Robert and Alma Moreton lecture: pay for performance: more than rearranging
      the deck chairs?
AB  - Over the past 30 years, research exploring the causes and consequences of
      geographic variations in practice has called into question widely held
      assumptions about the relationship between spending and quality. Two-fold
      differences in spending are observed across U.S. regions that are not due to
      differences in illness or to the prices charged by providers. Rather, higher
      spending is due primarily to greater use of "supply-sensitive" services: the
      frequency of visits to physicians and referrals to specialists, the amount of
      time similar patients spend in the hospital, and the frequency of imaging, tests,
      and minor procedures. The paradox, however, is that greater use of these services
      has been shown to be associated with lower quality, no gain in survival, and
      worse physician and patient-reported quality of care. It may be possible,
      therefore, to lower spending while improving quality. But this will require
      addressing the underlying causes of the variations: overuse of discretionary
      services in a fee-for-service system that ensures that physicians stay busy and
      that existing capacity remains fully deployed. These findings point to 3
      strategies that will be required for pay for performance to achieve its
      potential: fostering local organizational accountability for the overall quality
      and costs of care--and for the capacity of the local delivery system; adoption of
      comprehensive longitudinal performance measures--to reassure the public that
      lower spending is compatible with higher quality care; and fundamental reform of
      the payment system.

PMID- 18047983
TI  - Recent trends in utilization rates of noncardiac thoracic imaging: an example of
      how imaging growth might be controlled.
AB  - PURPOSES: To study trends in the utilization of the various noncardiac thoracic
      imaging modalities in the Medicare population in recent years and to compare the
      roles of radiologists and nonradiologist physicians. MATERIALS AND METHODS: The
      Medicare Part B databases for 1996 through 2005 were reviewed. All Current
      Procedural Terminology, Fourth Edition, codes pertaining to noninvasive imaging
      of noncardiac thoracic structures were selected and grouped into 5 categories:
      chest radiography (CXR), chest computed tomography (CT)/computed tomographic
      angiography (CTA), noncardiac radionuclide scans, ultrasound, and magnetic
      resonance imaging/magnetic resonance angiography. Utilization rates per 1,000
      Medicare beneficiaries were calculated. Medicare physician specialty codes were
      used to ascertain utilization by radiologists compared with nonradiologist
      physicians. Trends over the 9-year period were studied. RESULTS: In 1996, a total
      of 1,044.1 noncardiac thoracic imaging examinations were performed per 1,000
      Medicare beneficiaries, increasing to 1,051.6 in 2005 (+1%). In the largest
      category, CXR, the utilization rate dropped from 995.2 in 1996 to 941.5 in 2005 (
      5%). The radionuclide scan utilization rate also dropped, from 16.9 in 1996 to
      8.3 in 2005 (-51%). By contrast, the chest CT/CTA utilization rate increased from
      30.9 in 1996 to 99.7 in 2005 (+223%). The use of magnetic resonance
      imaging/magnetic resonance angiography and ultrasound in the thorax was minimal.
      In 2005, radiologists performed 91% of CXR studies, 97% of chest CT/CTA studies,
      and 94% of noncardiac chest radionuclide scans. CONCLUSIONS: The overall
      utilization rate of noncardiac chest imaging in recent years has increased only
      minimally. Within the various categories, there has been a decline in CXR
      utilization and a substantial decline in radionuclide scan utilization. However,
      there has been a considerable increase in the utilization of chest CT/CTA.
      Radiologists strongly predominate in all aspects of noncardiac thoracic imaging.
      This seems to be a pattern in which the use of a newer and better technology, CT
      or CTA, gradually replaces older ones and overall utilization rates remain
      relatively flat. One reason for this seems to be the lack of major involvement by
      nonradiologist physicians who might be in a position to self-refer. It is in
      contradistinction to cardiac imaging, in which the utilization of radionuclide
      scans and echocardiography has sharply increased among cardiologists. These data
      suggest that utilization rates in imaging might be kept under control by
      eliminating the opportunity for self-referral.

PMID- 18047984
TI  - Economics of radiology report editing using voice recognition technology.
AB  - As voice recognition technology takes hold in radiology practices, independent
      and hospital-based practices are faced with a decision of who should be
      responsible for the report-editing process, radiologists or transcriptionists.
      Although a radiologist's time is expensive compared with a transcriptionist's, if
      certain other conditions prevail, it may be possible to eliminate
      transcriptionists from the report generation process. Among these conditions are
      political, budgeting, psychosocial, and economic constraints. The author presents
      an econometric model that examines the economic issues involved in such a
      decision. Practices, both academic and private, can use this model to help
      determine which course of action makes the most economic sense. This is not
      always obvious.

PMID- 18047985
TI  - Re: "Economics of radiology report editing using voice recognition technology".

PMID- 18047986
TI  - Preserving digital images for legal proceedings.
AB  - The legal principles governing the use of radiologic images in court and other
      legal proceedings were developed before the introduction of computers in
      radiology and nuclear medicine imaging equipment. Modern digital images present a
      wide variety of new concerns that are not adequately addressed by the principles
      used by most lawyers and courts. This article discusses the most important of
      these new concerns, such as being able to prove that an image has not been
      altered and being able to prove that the hardware and software used to create it
      were scientifically reliable. A nonexhaustive set of recommendations are given to
      guide radiologists in beginning to review the image preservation procedures of
      their practices.

PMID- 18047987
TI  - Entering-class enrollments in educational programs in radiography, radiation
      therapy, and nuclear medicine technology, 1999 to 2006.
AB  - PURPOSE: To track entering-class enrollments in primary programs in radiography,
      nuclear medicine technology, and radiation therapy and to anticipate trends in
      numbers entering those disciplines. METHODS: The American Society of Radiologic
      Technologists' annual Enrollment Snapshot of Radiography, Radiation Therapy, and
      Nuclear Medicine Educational Programs has surveyed program directors in these 3
      disciplines every fall since 2001, obtaining information on entering-class
      enrollments, retention rates, and program viability. RESULTS: These survey
      results, together with American Registry of Radiologic Technologists statistics
      on the number of first-time certification examinees (which they foreshadow by
      about 2 years) show that the number of radiologic technologists entering these 3
      disciplines declined steadily from 1995 to 2000, then increased steadily from
      2000 to 2005. However, since 2005, entering-class enrollments have begun to level
      off, especially in radiation therapy and radiography. CONCLUSIONS: Entering-class
      enrollments provide an "early warning system" with respect to trends in the
      supply of radiographers, nuclear medicine technologists, and radiation
      therapists. Given the recent stabilization of entering-class enrollments in
      radiography and radiation therapy, we can anticipate a similar leveling off of
      the number of entrants into those 2 disciplines over the next 2 years.

PMID- 18047988
TI  - The triumvirate: a new model for residency program directorship.
AB  - The authors describe their initial 5-year experience with a new model of
      residency directorship: a triumvirate of shared leadership consisting of a
      director and 2 associate directors with specific areas of expertise and assigned
      responsibility. The major appeal of this model is its potential to draw on the
      diverse talents of 3 individuals with responsibilities matched to their specific
      areas of strength. A major benefit of the model is that each director has more
      time and energy to devote to specific duties, resulting in a greater opportunity
      for innovation and creativity. In this article, the authors describe the roles,
      responsibilities, and accomplishments of each of the 3 directors. They also
      discuss potential benefits of the triumvirate model in comparison with a
      traditional residency directorship and potential pitfalls to avoid when
      implementing this model.

PMID- 18047989
TI  - Promoting educational innovation: lessons from the request for proposals for ACR
      Appropriateness Criteria Usage in Medical Education.
AB  - This article describes the development of a new ACR grant program, ACR
      Appropriateness Criteria Usage in Medical Education. Developed and funded over
      the course of a single year, the program provides grants totaling up to $60,000
      annually to support innovation in radiology education. The development and
      implementation of this program provides lessons that can help radiology educators
      and leaders craft a brighter future for radiology education.

PMID- 18047990
TI  - Too much information! What we need from IT beyond image manipulation tools.

PMID- 18047991
TI  - CT colonography: current and future applications.

PMID- 18047992
TI  - ALARA in pediatric fluoroscopy.

PMID- 18047993
TI  - Fixing our profession: the training not covered in residency.

PMID- 18047994
TI  - George Tievsky.

PMID- 18047995
TI  - Re: Apathy--the threat within.

PMID- 18047997
TI  - [Natraemia, natriuresis, inhibitors of sodium transport and high blood pressure].

PMID- 18047998
TI  - [New insights in the pathophysiology of preeclampsia and potential therapeutic
      implications].
AB  - Preeclampsia still represents the leading cause of feto-maternal morbi-mortality
      in developed countries. The reason for the persistence of such gravity results to
      a large extent from the lack of clear knowledge concerning the pathophysiology of
      this disease and consequently the lack of adequate therapy apart from placental
      extraction. Preeclampsia is the clinical result of a generalized maternal
      systemic endothelial dysfunction secondary to an abnormal placental development.
      The close mechanisms of the abnormal placental development remain elusive.
      Currently, only epidemiologic risk factors and some immuno-genetic dysfunctions
      have been identified to favour abnormal placentation and preeclampsia. On the
      other hand, the identification of two circulating anti-angiogenic proteins, the
      soluble-fms-like tyrosine kinase-1 and the soluble endoglin, produced in excess
      by the placenta during the preeclampsia, allow us now to connect clearly abnormal
      placentation to an endothelial dysfunction. The excessive production of these two
      anti-angiogenic proteins induces an endothelial dysfunction by inhibiting
      circulating proangiogenic factors such as the placental growth factor, the
      vascular endothelial growth factor but also the transforming growth factor-beta.
      So far, numerous placental factors have been proposed, however none has been able
      to induce a real typical phenotype of preeclampsia. This discovery has two
      potential medical impacts. Firstly, the potential possibility, in the future, to
      measure these surrogate markers in the blood or urine to predict the onset of
      preeclampsia before its clinical manifestations. Secondly the theoretical
      possibility to reverse the angiogenic imbalance state of preeclamspsia and
      consequently to correct the maternal syndrome transiently by adding exogenous
      proangiogenic factor.

PMID- 18047999
TI  - [Renal transplantation in patients with autosomal dominant polycystic kidney
      disease: pre-transplantation evaluation and follow-up].
AB  - Autosomal dominant polycystic kidney disease (ADPKD) which accounts for 15% of
      all renal transplantations emerges as the third cause of kidney transplantation
      in France. In addition to routine evaluation before transplantation, the ADPKD
      patient requires special assessment of three aspects: should potential kidney
      complications (recurrent upper tract infection or haemorrhage) or kidney size
      assessed by computed tomography require nephrectomy prior to transplantation? Is
      it advisable to detect intracranial aneurysm (ICA) in patients with a relative
      having experienced ruptured ICA? When transplantation from a living relative is
      considered, the existence of ADPKD in the donor should be formally ruled out by
      imaging or genetic studies. The risk of recurrence of ADPKD post-transplantation
      does not exist. Nevertheless other complications may occur. Thus, an increased
      incidence of colonic perforation has been reported. In addition, as compared to
      non-ADPKD patients, an increased risk for both skin cancer and new-onset post
      transplant diabetes mellitus has been reported recently after kidney
      transplantation. Finally, because these patients suffer from an inherited
      syndrome, physicians should carefully consider the personal and familial history
      before and after transplantation in order to respond to fatalism in some cases,
      or to attenuate excessive enthusiasm in the others. Altogether, it apears that a
      specific approach is needed for ADPKD patients when considering renal
      transplantation.

PMID- 18048000
TI  - [Characteristics of potential living kidney donors in Ivory Coast: a survey prior
      to a project of kidney transplantation in French Black Africa].
AB  - The source of living kidney donors in the general population remains underused.
      The present study aims at assessing the prevalence and the characteristics of
      potential living kidney donors in Ivory Coast in a view of a project of kidney
      transplantation in French Black Africa. A survey was undertaken in Abidjan from
      30 June to 7 July 2006. Nine hundred (and) sixty-two subjects living in the
      capital and aged between 19 and 64 years old were randomly chosen using data from
      the 1998 population census. Subjects were asked their age, gender, nationality,
      marital status, information on kidney graft and renal failure, and their
      willingness to donate kidney to a relative or friend for transplantation purpose.
      Seventy per cent of the population study appeared favourable to kidney donation.
      Potentials living kidney donors have displayed following characteristics: age
      inferior to 26 years old [OR=2.08, P<0.02, 95%CI: 1.10-3.92]; Ivorians national
      [OR=2.72, P<0.002, 95% CI 1.42-5.21]; having heard of kidney transplantation
      (OR=1.89, P<0.047, 95% CI 1-3.54]); the death of a relative or friend from renal
      failure [OR=1.82, P<0.002, 95% CI 1.25 2.67]. Being married adversely affect
      kidney donation [OR=0.52, P<0.0002, 95% CI 0.34-0.79]. Potentials living kidney
      donors are in great number in Ivory Coast, who had specific characteristics.

PMID- 18048001
TI  - [Indinavir-associated tubulointerstitial renal disease].
AB  - Indinavir, used for the treatment of HIV disease, forms distinctive crystals in
      the urine. The crystalluria has been associated principally with several urinary
      tract abnormalities which may require discontinuation of the drug. We present a
      case of progressive leucocyturia and renal impairment occurring during indinavir
      treatment which illustrates vividly the impact of the crystalluria on the
      tubulointerstitial renal compartment.

PMID- 18048002
TI  - [Cardiovascular consequences of sleep apnea].
AB  - A growing body of epidemiologic, experimental, and therapeutic data supports an
      association between sleep disordered breathing and cardiovascular morbidity and
      mortality. Pathophysiologic mechanisms including sympathetic activation,
      oxidative stress, systemic inflammation, hyperleptinemia, insulin resistance,
      lipidic peroxydation, may influence the development and progression of
      hypertension, ischemic cardiopathy, cardiac rythm disturbances, cardiac failure,
      renal failure and stroke. Treatment of apneas is associated with a decrease in
      new cardiovascular events. These results support the importance of recognising,
      treating, and if possible preventing OSA.

PMID- 18048003
TI  - [Bibliographic medical research using MEDLINE-PubMed. A practical approach based
      on examples].

PMID- 18048004
TI  - Failure to condition to a cue is associated with sustained contextual fear.
AB  - The acquisition of a conditioned fear response is adaptive, as it enables the
      organism to appropriately respond to predictors of aversive events. Consequently,
      the absence of predictive cues can be used as a signal for safety. We aimed to
      study whether deficient fear conditioning might lead to maladaptive fear.
      Following previous work, we predicted that failure to learn the CS-US association
      would result in higher contextual fear, and that participants who failed to learn
      would tend to exhibit higher trait anxiety. Conditioning took place in a virtual
      environment with two contexts. In one of the two contexts, offset of a CS (light)
      was associated with a shock. Each participant visited two places (a house and an
      apartment) in each of 12 blocks. In one of these places shocks were administered
      at the offset of an 8-s period of lights on (CS). The results showed that half of
      the participants demonstrated differential shock expectancy between situations in
      the shock context in which the CS was present versus absent. This indicates that
      these participants learned the contingencies between the shocks and both the
      context and the light CS. In contrast, the other half of the participants learned
      only the association with the context. As predicted, learning the CS-US
      contingency resulted in reduced self-reported fear in the absence of the CS in
      the danger context compared to the presence of the CS. On the other hand,
      participants who failed to learn the association displayed a sustained aversive
      state throughout the duration of the danger context. Skin conductance measures
      confirmed this pattern of results. Fear-potentiated startle during the threat
      context compared to the safe context was significant in both groups, while
      startle was only potentiated during the CS in the threat context in the group
      that learned the CS association (trend-level significant). Finally, scores on
      Spielberger's self-report scale of trait anxiety tended to be higher in the group
      of participants who did not learn the CS-shock association in the danger context
      compared to participants who did. In conclusion, these results confirm higher
      contextual fear in participants who did not acquire a conditioned response to the
      cue in comparison to participants who did. Also, virtual reality contexts provide
      a useful tool for the study of context conditioning.

PMID- 18048005
TI  - The locations of mitochondria in mammalian photoreceptors: relation to retinal
      vasculature.
AB  - Adult mammalian photoreceptors are elongated cells, and their mitochondria are
      sequestered to the ends of the cell, to the inner segments and (in some species)
      to axon terminals in the outer plexiform layer (OPL). We hypothesised that
      mitochondria migrate to these locations towards sources of oxygen, from the
      choroid and (in some species) from the deep capillaries of the retinal
      circulation. Six mammalian species were surveyed, using electron and light
      microscopy, including immunohistochemistry for the mitochondrial enzyme
      cytochrome oxidase (CO). In all 6 species, mitochondria were absent from
      photoreceptor somas and were numerous in inner segments. Mitochondria were
      prominent in axon terminals in 3 species (mouse, rat, human) with a retinal
      circulation and were absent from those terminals in 3 species (wallaby, rat,
      guinea pig) with avascular retinas. Further, in a human developmental series, it
      was evident that mitochondria migrate within rods and cones, towards and
      eventually past the outer limiting membrane (OLM), into the inner segment. In
      Muller and RPE cells also, mitochondria concentrated at the external surface of
      the cells. Neurones located in the inner layers of avascular retinas have
      mitochondria, but their expression of CO is low. Mitochondrial locations in
      photoreceptors, Muller and RPE cells are economically explained as the result of
      migration within the cell towards sources of oxygen. In photoreceptors, this
      migration results in a separation of mitochondria from the nuclear genome; this
      separation may be a factor in the vulnerability of photoreceptors to mutations,
      toxins and environmental stresses, which other retinal neurones survive.

PMID- 18048006
TI  - Sodium intake by hyperosmotic rats treated with a GABA(A) receptor agonist into
      the lateral parabrachial nucleus.
AB  - Inhibitory mechanisms in the lateral parabrachial nucleus (LPBN) and central
      GABAergic mechanisms are involved in the regulation of water and NaCl intake.
      Besides increasing fluid depletion-induced sodium intake, the activation of
      GABA(A) receptors with muscimol into the LPBN also induces ingestion of 0.3 M
      NaCl in normonatremic, euhydrated rats. It has been suggested that inhibitory
      mechanisms activated by osmotic signals are blocked by GABA(A) receptor
      activation in the LPBN, thereby increasing hypertonic NaCl intake. Therefore, in
      the present study we investigated the effects of muscimol injected into the LPBN
      on water and 0.3 M NaCl intake in hyperosmotic cell-dehydrated rats (rats treated
      with an intragastric load of 2 M NaCl). Male Wistar rats with stainless steel
      cannulas implanted bilaterally into the LPBN were used. In euhydrated rats,
      muscimol (0.5 nmol/0.2 microl), bilaterally injected into the LPBN, induced
      ingestion of 0.3 M NaCl (24.6+/-7.9 vs. vehicle: 0.5+/-0.3 ml/180 min) and water
      (6.3+/-2.1 vs. vehicle: 0.5+/-0.3 ml/180 min). One hour after intragastric 2 M
      NaCl load (2 ml), bilateral injections of muscimol into the LPBN also induced 0.3
      M NaCl intake (22.1+/-5.2 vs. vehicle: 0.9+/-0.8 ml/210 min) and water intake
      (16.5+/-3.6 vs. vehicle: 7.8+/-1.8 ml/210 min). The GABA(A) antagonist
      bicuculline (0.4 nmol/0.2 microl) into the LPBN reduced the effect of muscimol on
      0.3 M NaCl intake (7.1+/-2.1 ml/210 min). Therefore, the activation of GABA(A)
      receptors in the LPBN induces ingestion of 0.3 M NaCl by hyperosmotic cell
      dehydrated rats, suggesting that plasma levels of renin or osmolarity do not
      affect sodium intake after the blockade of LPBN inhibitory mechanisms with
      muscimol.

PMID- 18048007
TI  - Glycine modulates synaptic NR2A- and NR2B-containing NMDA receptor-mediated
      responses in the rat visual cortex.
AB  - In the central nervous system, activation of N-methyl-d-aspartate receptor (NMDA
      R) glycine binding sites is a prerequisite for activation of synaptic NMDA-Rs by
      the excitatory neurotransmitter glutamate. Here we used patch-clamp recordings in
      transverse slice preparations to study whether the glycine binding site of the
      NMDA-R saturates and to determine their subunit composition in layer II/III
      pyramidal neurons of the rat visual cortex. We found that the NMDA-R-mediated
      component of miniature excitatory postsynaptic currents (mEPSCs) could be
      potentiated by exogenously applied glycine. Similar results were obtained by
      exogenously applied d-serine. A specific antagonist for NR2B-NMDA-Rs, Ro 25-6981,
      reduced NMDA-R-mediated mEPSCs, and glycine with Ro 25-6981 enhanced NMDA-R
      mediated mEPSCs. Moreover, Zn2+, an NR2A-NMDA-R antagonist, also reduced NMDA
      mediated mEPSCs and glycine with Zn2+ enhanced the NMDA-mediated mEPSCs. Our data
      indicate that the glycine binding site of synaptic NR2A-containing and NR2B
      containing NMDA-Rs does not saturate and that glycine may act as a modulator of
      NMDA-R-mediated transmission in layer II/III pyramidal neurons of the rat visual
      cortex.

PMID- 18048008
TI  - Hemispheric asymmetries in the perceptual representations of words.
AB  - The representation of words in sentences can involve the activation and
      integration of perceptual information. For example, readers who are asked to view
      pictures of objects relating to a word in a sentence are influenced by perceptual
      information in the sentence context-readers are faster to respond to a picture of
      a whole apple after reading, "There is an apple in the bag," than after reading,
      "There is an apple in the salad." The purpose of this study was to examine how
      the two cerebral hemispheres use perceptual information about words as a function
      of sentence context. Patients who had damage to the left or right hemisphere and
      age-matched control participants read sentences that described, but did not
      entail, the shape or state of an object. They then made recognition judgments to
      pictures that either matched or mismatched the perceptual form implied by the
      sentence. Responses and latencies were examined for a match effect -- faster and
      more accurate responses to pictures in the match than mismatch condition --
      controlling for comprehension ability and lesion size. When comprehension ability
      and lesion size are properly controlled, left-hemisphere-damaged patients and
      control participants exhibited the expected match effect, whereas right
      hemisphere-damaged participants showed no effect of match condition. These
      results are consistent with research implicating the right hemisphere in the
      representation of contextually relevant perceptual information.

PMID- 18048009
TI  - Involvement of spinal Met-enkephalin in nicotine-induced antinociception in mice.
AB  - Nicotine is neuronal stimulating drug in the central nervous system and elicits
      various effects through nicotinic acetylcholine receptors. As previously
      reported, nicotine has an antinociceptive effect through activation of endogenous
      opioid neurons. However, detailed mechanisms of nicotine-induced antinociception
      are uncertain. In this study, we focused on spinal cord and investigated the
      involvement of endogenous opioidergic neurons in nicotine-induced antinociception
      in mice. In the tail-pinch test, subcutaneously administered nicotine (5 mg/kg)
      produced maximal antinociception 0.5 h after nicotine administration; this was
      attenuated by mecamylamine (MEC, 3 mg/kg, s.c.) or naloxone (NLX, 1 mg/kg, s.c.)
      administration. Intrathecal nicotine (10 mug) produced maximal antinociception at
      2 min and this was also attenuated by MEC (3 mg/kg, s.c.) or NLX (1 mg/kg, s.c.)
      administration. The preproenkephalin (ppENK) mRNA level in spinal cord, but not
      dorsal root ganglion, was significantly increased 2 h following nicotine
      administration and recovered to control level 4 h after nicotine (5 mg/kg, s.c.)
      administration. This increase in ppENK mRNA level was inhibited by MEC (3 mg/kg,
      s.c.). The mRNA levels of preprodynorphin and preproopiomelanocortin were not
      increased by nicotine (5 mg/kg, s.c.). In the dorsal horn of the lumbar spinal
      cord, methionine-enkephalin (Met-ENK)-like IR was remarkably reduced at 0.5 h
      following nicotine administration and recovered to control levels by 2 h after
      nicotine (3 mg/kg, s.c.) administration. These results suggest that nicotine has
      an antinociceptive effect by promoting the release of Met-ENK, but not dynorphins
      and endorphins, from activated opioidergic neurons in spinal cord.

PMID- 18048010
TI  - Voltage-gated potassium currents within the dorsal vagal nucleus: inhibition by
      BDS toxin.
AB  - Voltage-gated potassium (Kv) channels are essential components of neuronal
      excitability. The Kv3.4 channel protein is widely distributed throughout the
      central nervous system (CNS), where it can form heteromeric or homomeric Kv3
      channels. Electrophysiological studies reported here highlight a functional role
      for this channel protein within neurons of the dorsal vagal nucleus (DVN).
      Current clamp experiments revealed that blood depressing substance (BDS) and
      intracellular dialysis of an anti-Kv3.4 antibody prolonged the action potential
      duration. In addition, a BDS sensitive, voltage-dependent, slowly inactivating
      outward current was observed in voltage clamp recordings from DVN neurons.
      Electrical stimulation of the solitary tract evoked EPSPs and IPSPs in DVN
      neurons and BDS increased the average amplitude and decreased the paired pulse
      ratio, consistent with a presynaptic site of action. This presynaptic modulation
      was action potential dependent as revealed by ongoing synaptic activity. Given
      the role of the Kv3 proteins in shaping neuronal excitability, these data
      highlight a role for homomeric Kv3.4 channels in spike timing and
      neurotransmitter release in low frequency firing neurons of the DVN.

PMID- 18048011
TI  - Effects of stimulus-response compatibility in mediating expert performance in
      baseball players.
AB  - The purpose of this study was to examine whether the baseball players' shorter
      Go/Nogo reaction time (RT) was influenced by stimulus-response compatibility
      (SRC) effects. To accomplish this purpose, we examined RTs and event-related
      potential components in three Go/Nogo tasks, manipulating stimulus-response
      relations. The participants were nine college baseball players (Baseball) and
      nine college non-baseball players (Control). Task conditions were the following:
      spatial condition with baseball batting-specific S-R mapping (Spatial-BB) demands
      response execution or inhibition corresponding to spatial stimulus location. This
      condition was similar to the stimulus-response relations in baseball batting. The
      other two tasks demand their response based on the stimulus location or colors.
      These tasks did not have any baseball-specific stimulus-response relations. As a
      result of RTs, baseball players revealed shorter RTs in Spatial-BB than other
      tasks, but the control group showed similar RTs among three tasks. In Go trials,
      as for the interval between stimulus and lateralized readiness potential (LRP)
      onset which is the duration to the end of response selection, baseball players
      had shorter than control in Spatial-BB, whereas P300 latency and the interval
      between LRP and response did not show any difference between groups or among
      tasks. In Nogo trials, the augmented P300 amplitude of baseball players at
      frontal (Fz) was observed in Spatial-BB. The P300 amplitude in Nogo trials is
      often interpreted as the strength of inhibition. These results indicated that the
      facilitation of RTs in baseball players is likely due to a faster response
      selection and stronger inhibition caused by SRC effects in relation to specific S
      R mapping.

PMID- 18048012
TI  - Expression of survivin and p16(INK4a)/Cdk6/pRB proteins and induction of
      apoptosis in response to radiation and cisplatin in meningioma cells.
AB  - Although meningiomas represent the most common class of tumors of the central
      nervous system, the molecular events underlying their genesis and development are
      still not well defined, and therapeutic approaches based on the genetics of these
      tumors are currently lacking. In the present study we have used the
      immunoblotting technique to show that the p16(INK4A), Cdk6 and pRB proteins are
      differentially expressed in primary meningioma cells with 20-, 30- and 36-fold
      difference between the lowest and the highest levels of each protein,
      respectively. In addition, we present evidence that the level of the anti
      apoptosis survivin protein is high in these benign tumors. Moreover, the annexin
      V-associated flow cytometry technique was used to show that 60% of meningioma
      cell cultures underwent apoptosis in response to both gamma-rays and cisplatin,
      and 50% of these cells exhibited significant sensitivity to hydroxyurea. These
      agents triggered apoptosis through the mitochondrial pathway, by increasing the
      Bax/Bcl-2 ratio. Interestingly, the induction of apoptosis following radiation
      and cisplatin was significant in all cells that expressed low levels of
      p16(INK4A), Cdk6 and pRB proteins. These data shed more light on the molecular
      biology of meningioma cells and suggest that survivin and proteins of the RB
      pathway could play a determinant role in the development and the treatment of
      meningiomas.

PMID- 18048014
TI  - FT-IR spectra of alginic acid block fractions in three species of brown seaweeds.
AB  - Sodium alginates obtained by alkaline extraction of Lessonia flavicans,
      Desmarestia ligulata and Desmarestia distans (Phaeophyta) from southern Chile
      were partially hydrolyzed with HCl. Each alginate gave three fractions that were
      characterized using FT-IR spectroscopy. The fractions soluble in 0.3M HCl
      presented in the fingerprint region four vibrations at around 960, 911, 890 and
      815 cm(-1) that were assigned to heteropolymeric blocks. The fractions soluble at
      pH 2.85 showed bands at around 948, 888 and 820 cm(-1) attributed to
      homopolymannuronic acid blocks, the first band is resolved in the second
      derivative spectra into two bands at 951 and 936 cm(-1). The fractions insoluble
      at pH 2.85 presented four bands at around 947, 903, 812 and 781 cm(-1), which
      were assigned to homopolyguluronic acid blocks. For some samples, the second
      derivative FT-IR spectra showed new bands indicating the presence of other
      structures, in low proportions. Structures deduced by FT-IR spectroscopy were
      corroborated by solution (1)H and (13)C NMR spectroscopy. Two-dimensional spectra
      were collected to confirm the fine structure of the hetero- and homopolymeric
      fractions. A geometrically optimized model for the disaccharide alpha-l
      gulopyranuronosyl-(1-->4)-alpha-l-gulopyranuronic acid was calculated using
      density functional theory; good agreement was obtained between its corresponding
      calculated vibrations and the experimental bands assigned to homopolyguluronic
      acid blocks.

PMID- 18048013
TI  - Glutathione production is regulated via distinct pathways in stressed and non
      stressed cortical neurons.
AB  - Peroxynitrite-mediated damage has been linked to numerous neurological and
      neurodegenerative diseases, including stroke, Alzheimer's and Parkinson's
      Diseases, amyotrophic lateral sclerosis and multiple sclerosis. Studies on the
      toxic effects of peroxynitrite in neurons have focused primarily on adverse
      effects resulting from the nitration of cellular proteins as the principal mode
      of toxicity while the consequences of the modulation of kinase pathways by
      peroxynitrite have received relatively less attention. Our results show that
      treatment of primary rat neurons with the peroxynitrite donor, SIN-1, leads to
      decreases in glutathione (GSH) levels and cell viability via a novel
      extracellular-signal-related kinase (ERK)/c-Myc phosphorylation pathway and a
      reduction in the nuclear expression of NF-E2-related factor-2 (Nrf2) that down
      regulate the expression of glutamate cysteine ligase, the rate limiting enzyme
      for GSH synthesis. The flavonoid fisetin protects against the SIN-1-mediated
      alterations in ERK/c-Myc phosphorylation, nuclear Nrf2 levels, glutamate cysteine
      ligase levels, GSH concentration and cell viability. We also show that inhibition
      of mitogen-activated protein kinase kinase or Raf kinase can increase GSH levels
      in unstressed primary rat neurons through the same ERK/c-Myc phosphorylation
      pathway. Together, these results demonstrate that distinct signaling pathways
      modulate GSH metabolism in unstressed and stressed cortical neurons.

PMID- 18048015
TI  - WAXS and 13C NMR study of Gluconoacetobacter xylinus cellulose in composites with
      tamarind xyloglucan.
AB  - - Model composites, produced using cellulose from stationary cultures of the
      bacterium Gluconoacetobacter xylinus and tamarind xyloglucan, were examined by
      wide-angle X-ray scattering (WAXS) and CP/MAS solid-state (13)C NMR spectroscopy.
      The dominant crystallite allomorph of cellulose produced in culture media with or
      without xyloglucan was cellulose I(alpha) (triclinic). The presence of xyloglucan
      in the culture medium reduced the cross-section dimensions of the cellulose
      crystallites, but did not affect the crystallite allomorph. However, when the
      composites were refluxed in buffer, the proportion of cellulose I(beta) allomorph
      increased relative to that of cellulose I(alpha). In contrast, cellulose I(alpha)
      remained the dominant form when cellulose, produced in the absence of xyloglucan,
      was then heated in the buffer. Hence the presence of xyloglucan has a profound
      effect on the formation of the cellulose crystallites by G. xylinus.

PMID- 18048016
TI  - Preparation of glycoconjugates by dialkyl squarate chemistry revisited.
AB  - The methyl 6-hydroxyhexanoyl glycoside of lactose was treated with each of 1,2
      diaminoethane or hydrazine hydrate, and the corresponding amino amide 4 and acyl
      hydrazide 13, were treated with each of squaric acid dimethyl, diethyl, dibutyl,
      and didecyl esters. The monoesters were conjugated to bovine serum albumin (BSA)
      at different concentrations of hapten using 0.05 and 0.5M pH 9 borate buffer.
      Maximum loading was achieved faster, and the conjugation efficiency was higher,
      when the conjugation was conducted at higher concentrations of both hapten and
      buffer. Conjugations involving haptens 14-17 prepared from hydrazide 13 were
      generally slower and less efficient than those with compounds 5-8, which were
      made from amino amide 4. Maintaining pH 9 during conjugation was found to be the
      most important factor in ensuring that the conjugation was a fast, highly
      efficient, and reproducible process. When the pH of the conjugation mixture fell
      during the reaction, resulting in decreased reaction rate or even termination of
      the conjugation process, the normal course of the conjugation process could be
      restored by addition of buffer salts. Hydrolysis studies with monoesters formed
      from amino amide 4 under conjugation conditions showed that decyl ester 8 was the
      most stable and that the methyl compound 5 was the one most readily hydrolyzed.
      The stability of monoesters prepared from hydrazide 13 was similar and comparable
      to the decyl ester prepared from 4. No definite advantage was found for the use
      of any of the four dialkyl squarate reagents (methyl-, ethyl-, butyl-, and decyl
      ) for conversion of carbohydrate derivatives to species amenable for conjugation.
      Nevertheless, dimethyl squarate seemed to be the most convenient reagent because
      it is a crystalline, easy to handle, and commercially available material with
      very good reactivity.

PMID- 18048017
TI  - Effect of pH on the association behavior in aqueous solutions of pig gastric
      mucin.
AB  - In this study, dynamic light scattering (DLS), turbidity, and rheo-small angle
      light scattering (rheo-SALS) methods have been utilized to examine the impact of
      pH (1 < or = pH < or = 7) on aqueous solutions of noncommercial purified pig
      gastric mucin. The asymmetric flow field-flow fractionation (AFFFF) measurements
      established that the mucin sample has a high molecular weight and is
      polydisperse. DLS measurements on dilute solutions of mucin disclosed large
      interchain aggregates at pH 2, where the polymer has a low charge density or is
      uncharged. At lower or higher values of pH, mucin is charged and the tendency of
      forming interpolymer complexes is affected. In the semidilute concentration
      regime, pronounced junction zones ('lumps' of polymer) are evolved and a
      heterogeneous connected network is formed at pH 2, whereas the association
      structures are disintegrated (smaller 'lumps') at lower or higher pH values due
      to electrostatic repulsive interactions, and a more homogeneous network is
      evolved. The DLS and viscosity results at pH 1 indicate the development of a
      fragmented network, composed of contracted chains that are decorated by some
      positive charges. The effect of shear flow on the structure of semidilute
      solutions of mucin was investigated with the aid of rheo-SALS methods. The
      scattered intensity revealed a strong upturn at low values of the wave vector (q)
      for mucin solutions at pH 2 and pH 4, which suggests the evolution of large
      association domains. At these pH values, a flow-induced anisotropy in the 2D SALS
      patterns in the form of elliptical shapes was observed at high shear rates.

PMID- 18048018
TI  - The effect of sodium chloride on molecular mobility in amorphous sucrose detected
      by phosphorescence from the triplet probe erythrosin B.
AB  - Phosphorescence from the triplet probe erythrosin B provides spectroscopic
      characteristics such as emission energy and lifetime that are specifically
      sensitive to molecular mobility of the local environment. This study used
      phosphorescence of erythrosin B to investigate how variation in NaCl content
      modulated the mobility of the amorphous sucrose matrix over the temperature range
      from 5 to 100 degrees C. Addition of NaCl increased the emission energy and the
      energy difference with excitation at the absorption maximum and the red edge, and
      increased the lifetime by reducing the non-radiative decay rate in the glass as
      well as in the undercooled liquid in a concentration dependent manner, indicating
      that NaCl decreased the matrix molecular mobility. Emission energy and lifetime
      increased with increasing NaCl content up to a maximum at NaCl/sucrose mole ratio
      of approximately 0.5; above 0.5 mole ratio, the effect of NaCl was less
      significant and appeared to be opposed by increasing plasticization by residual
      water. Changes in the width of the distribution of the emission energy and
      lifetime and variation in the lifetime with excitation and emission wavelength
      indicated that NaCl increased the spectral heterogeneity and thus increased the
      extent of dynamic site heterogeneity. These results are consistent with a
      physical model in which sodium and chloride ions interact with sucrose OH by ion
      dipole interactions, forming clusters of less mobile molecules within the matrix.

PMID- 18048019
TI  - Exploring specificity of glycosyltransferases: synthesis of new sugar nucleotide
      related molecules as putative donor substrates.
AB  - We investigated the specificity of glycosyltransferases toward donor substrates
      in two complementary directions. First we prepared simple N-acetyl-alpha-D
      glucosamine 1-diphosphates: methyl-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)
      diphosphate, benzyl-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-diphosphate, 4
      phenylbutyl-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-diphosphate, by the
      coupling of the corresponding activated alkyl phosphates with N-acetyl-alpha-D
      glucosamine 1-phosphate. These diphosphates as well as 2-acetamido-2-deoxy-alpha
      D-glucopyranose 1-diphosphate, tested as donors of N-acetylglucosamine in a
      reaction catalyzed by Neisseria meningitidis N-acetylglucosaminyltransferase
      (LgtA), proved to be devoid of activity. Evaluated as inhibitors, only 2
      acetamido-2-deoxy-alpha-D-glucopyranose 1-diphosphate showed some inhibitory
      activity with an IC50 value of 7 mM. In the second approach, we prepared sugar
      nucleotide mimics having the diphosphate bridge replaced by the
      oxycarbonylaminosulfonyl linker. The surrogate of GDP-Fuc was synthesized as a
      9:1 alpha/beta anomeric mixture, in 40% yield, starting from chlorosulfonyl
      isocyanate, perbenzylated l-fucopyranose, and a guanosine derivative, protected
      on the exocyclic amine and secondary hydroxyl functions of ribose. Then two
      deprotection steps, hydrogenolysis and enzymatic hydrolysis catalyzed by
      penicillin G amidase afforded the target molecule to be tested as fucose donor
      with recombinant human alpha-(1-->3/4)-fucosyltransferase (FucT-III). Tested as a
      4:1 alpha/beta anomeric mixture, both in the absence and in the presence of
      cationic cofactors, this new guanosine fucose conjugate proved to be ineffective.
      Its inhibitory activity toward FucT-III evaluated through a competition
      fluorescence assay was very poor (IC50 value of 20 mM). The surrogate of UDP
      GlcNAc that was already known as its protected acetylated derivative, tested as N
      acetylglucosamine donor with LgtA in the presence of Mn(2+) turned out not to be
      active either.

PMID- 18048020
TI  - Down modulation of human TLR3 function by a monoclonal antibody.
AB  - Toll-like receptors are a family of pattern-recognition receptors that contribute
      to the innate immune response. Toll-like receptor 3 (TLR3) signals in response to
      foreign, endogenous and synthetic ligands including viral dsRNA, bacterial RNA,
      mitochondrial RNA, endogenous necrotic cell mRNA and the synthetic dsRNA analog,
      poly(I:C). We have generated a monoclonal antibody (mAb CNTO2424) that recognizes
      the extracellular domain (ECD) of human TLR3 in a conformation-dependent manner.
      CNTO2424 down-regulates poly(I:C)-induced production of IL-6, IL-8, MCP-1,
      RANTES, and IP-10 in human lung epithelial cells. In addition, mAb CNTO2424 was
      able to interfere with the known TLR3-dependent signaling pathways, namely NF
      kappaB, IRF-3/ISRE, and p38 MAPK. The generation of this neutralizing anti-TLR3
      mAb provides a unique tool to better understand TLR3 signaling and potential
      cross-talk between TLR3 and other molecules.

PMID- 18048021
TI  - Increased expression and activation of IL-12-induced Stat4 signaling in the
      mucosa of ulcerative colitis patients.
AB  - Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative
      colitis (UC), are chronic inflammatory diseases with unsolved pathogenesis.
      Imbalanced Th1/Th2 may play a role in the sustained inflammation of IBD. In
      China, CD is rare but the incidence of UC has been rising steadily in the last
      two decades. We investigated the expression of IL-12 (p40) and IFN-gamma, and the
      activational state of Stat4 signaling in mucosal tissues at the site of disease
      from 30 active UC patients in comparison with 30 healthy controls. RT-PCR
      analyses revealed increased mRNA expression of IL-12 (p40) but not IFN-gamma in
      UC patients. Western blot analyses discovered, for the first time, increased
      levels of constitutive Stat4 in the cytoplasm and phosphorylated Stat4 in the
      nucleus of mucosal cells from UC patients. We conclude that a heightened, perhaps
      persistent, activational state of IL-12/Stat4, and/or IL-23/Stat4 signaling may
      be present in active Chinese UC patients, and possibly involved in chronic
      inflammation in UC.

PMID- 18048022
TI  - National Academy of Clinical Biochemistry Laboratory Medicine Practice
      Guidelines: clinical utilization of cardiac biomarker testing in heart failure.

PMID- 18048023
TI  - Drosophila ESC-like can substitute for ESC and becomes required for Polycomb
      silencing if ESC is absent.
AB  - The Drosophila esc-like gene (escl) encodes a protein very similar to ESC. Like
      ESC, ESCL binds directly to the E(Z) histone methyltransferase via its WD region.
      In contrast to ESC, which is present at highest levels during embryogenesis and
      low levels thereafter, ESCL is continuously present throughout development and in
      adults. ESC/E(Z) complexes are present at high levels mainly during embryogenesis
      but ESCL/E(Z) complexes are found throughout development. While depletion of
      either ESCL or ESC by RNAi in S2 and Kc cells has little effect on E(Z)-mediated
      methylation of histone H3 lysine 27 (H3K27), simultaneous depletion of ESCL and
      ESC results in loss of di- and trimethyl-H3K27, indicating that either ESC or
      ESCL is necessary and sufficient for di- and trimethylation of H3K27 in vivo.
      While E(Z) complexes in S2 cells contain predominantly ESC, in ESC-depleted S2
      cells, ESCL levels rise dramatically and ESCL replaces ESC in E(Z) complexes. A
      mutation in escl that produces very little protein is viable and exhibits no
      phenotypes but strongly enhances esc mutant phenotypes, suggesting they have
      similar functions. esc escl double homozygotes die at the end of the larval
      period, indicating that the well-known "maternal rescue" of esc homozygotes
      requires ESCL. Furthermore, maternal and zygotic over-expression of escl fully
      rescues the lethality of esc null mutant embryos that contain no ESC protein,
      indicating that ESCL can substitute fully for ESC in vivo. These data thus
      indicate that ESC and ESCL play similar if not identical functions in E(Z)
      complexes in vivo. Despite this, when esc is expressed normally, escl appears to
      be entirely dispensable, at least for development into morphologically normal
      fertile adults. Furthermore, the larval lethality of esc escl double mutants,
      together with the lack of phenotypes in the escl mutant, further suggests that in
      wild-type (esc(+)) animals it is the post-embryonic expression of esc, not escl,
      that is important for development of normal adults. Thus escl appears to function
      in a backup capacity during development that becomes important only when normal
      esc expression is compromised.

PMID- 18048024
TI  - Maintenance of genomic methylation patterns during preimplantation development
      requires the somatic form of DNA methyltransferase 1.
AB  - DNA methylation at cytosine residues in CpG dinucleotides is a component of
      epigenetic marks crucial to mammalian development. In preimplantation stage
      embryos, a large part of genomic DNA is extensively demethylated, whereas the
      methylation patterns are faithfully maintained in certain regions. To date, no
      enzymes responsible for the maintenance of DNA methylation during preimplantation
      development have been identified except for the oocyte form of DNA (cytosine-5)
      methyltransferase 1 (Dnmt1o) at the 8-cell stage. Herein, we demonstrate that the
      somatic form of Dnmt1 (Dnmt1s) is present in association with chromatin in MII
      stage oocytes as well as in the nucleus throughout preimplantation development.
      At the early one-cell stage, Dnmt1s is asymmetrically localized in the maternal
      pronuclei. Thereafter, Dnmt1s is recruited to the paternal genome during
      pronuclear maturation. During the first two cell cycles after fertilization,
      Dnmt1s is exported from the nucleus in the G2 phase in a CRM1/exportin-dependent
      manner. Antibody microinjection and small interfering RNA-mediated knock-down
      decreases methylated CpG dinucleotides in repetitive intracisternal A-type
      particle (IAP) sequences and the imprinted gene H19. These results indicate that
      Dnmt1s is responsible for the maintenance methylation of particular genomic
      regions whose methylation patterns must be faithfully maintained during
      preimplantation development.

PMID- 18048026
TI  - Opioid receptors are involved in the sedative and antinociceptive effects of
      hesperidin as well as in its potentiation with benzodiazepines.
AB  - Previous reports from our laboratory described the sedative activity of
      hesperidin (hesperetin-7-rhamnoglucoside). This property is greatly increased
      when the glycoside is injected jointly with diazepam and this interaction has
      been shown to be synergistic. In the present work the generality of the
      synergistic phenomenon is proved, since potentiation also occurs with several
      other benzodiazepines, namely alprazolam, bromazepam, midazolam and
      flunitrazepam. In order to advance in the study of the mechanism of action of
      hesperidin, the possible participation of several brain receptors, which are
      implicated in the control of numerous behavioral and physiological functions, was
      explored by investigating the effects of a variety of their antagonists on
      hesperidin actions. The results showed that the 5-HT2 receptor and the alpha1
      adrenoceptor seem unlikely to be involved in the behavioral effects of
      hesperidin. Naltrexone, a nonselective antagonist of opioid receptors, totally
      blocked hesperidin effects on locomotion, and partially antagonized hesperidin
      induced decreased exploration in the hole board test. Nor-binaltorphimine, a
      selective kappa opioid receptor antagonist, was able to partially block
      hesperidin effects on locomotor activity. Furthermore, hesperidin-induced
      antinociception was partially blocked by naltrexone, and potentiated by co
      administration with alprazolam. Hence, the participation of the opioid system in
      the sedative, antinociceptive and potentianting effects of hesperidin with
      benzodiazepines in mice is highly probable. Our results suggest a possible
      beneficial use of the association of hesperidin with benzodiazepines, not only to
      improve human sedative therapy, but also in the management of pain.

PMID- 18048025
TI  - AMP-activated protein kinase is involved in hormone-induced mouse oocyte meiotic
      maturation in vitro.
AB  - We have previously shown that AMP-activated protein kinase (AMPK) can induce the
      resumption of meiosis in mouse oocytes maintained in meiotic arrest in vitro. The
      present study was carried out to determine whether AMPK activation is involved in
      hormone-induced maturation. Follicle-stimulating hormone (FSH) and the EGF-like
      peptide, amphiregulin (AR), are potent inducers of maturation in cumulus cell
      enclosed oocytes (CEO). Within 3 h of FSH treatment, phospho-acetyl CoA
      carboxylase (ACC) levels were increased in germinal vesicle (GV)-stage oocytes
      when compared to non-stimulated controls and remained elevated throughout 9 h of
      culture, indicating AMPK activation. A similar response to AR was observed after
      6 h of culture. Using anti-PT172 antibody (binds only to activated AMPK), Western
      analysis demonstrated active AMPK in both FSH- or AR-treated GV-stage oocytes
      within 6 h. The AMPK inhibitors, compound C and adenine 9-beta-d
      arabinofuranoside (araA), blocked FSH- or AR-induced meiotic resumption and ACC
      phosphorylation, further supporting a causal role for AMPK in hormone-induced
      meiotic resumption. Immunocytochemistry using anti-PT172-AMPK antibody showed an
      increased diffuse cytoplasmic staining and more intense punctate staining in the
      germinal vesicles of oocytes following treatment with the AMPK activator 5
      aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) or with FSH or AR,
      and this staining was eliminated by compound C or a blocking peptide for the anti
      PT172 antibody. Staining of oocytes from hCG-stimulated mice with the anti-PT172
      antibody also showed pronounced label in the germinal vesicles within 1-2 h.
      Furthermore, in oocytes from all groups, active AMPK was always observed in
      association with the condensed chromosomes of maturing oocytes. Taken together,
      these results support a role for AMPK in FSH and AR-induced maturation in vitro
      and hCG-induced maturation in vivo.

PMID- 18048027
TI  - Effects of dual endothelin receptor blockade on sympathetic activation and
      arrhythmogenesis during acute myocardial infarction in rats.
AB  - The effects of dual (ETA and ETB) endothelin receptor blockade on ventricular
      arrhythmogenesis during acute myocardial infarction are not well defined. We
      randomly allocated Wistar rats to bosentan (100 mg/kg daily, n=24), a dual
      endothelin receptor antagonist, or vehicle (n=23). After 7 days of treatment,
      myocardial infarction was induced by permanent coronary ligation. Ventricular
      tachyarrhythmias were evaluated for 24 h following ligation, using a miniature
      telemetry electrocardiogram recorder. Action potential duration was measured from
      monophasic epicardial recordings and sympathetic activation was assessed by heart
      rate variability and catecholamine serum level measurements. Compared to controls
      (1012+/-185 s), bosentan (59+/-24 s) markedly decreased (P<0.00001) the total
      duration of ventricular tachyarrhythmias during the delayed (1-24 h) phase post
      ligation, with a modest effect during the early (0-1 h) phase (132+/-38 s, versus
      43+/-18 s, respectively, P=0.053). Treatment did not affect infarct size or total
      mortality. Action potential duration at 90% repolarization prolonged in controls
      (from 93.1+/-4.7 ms to 117.6+/-6.9 ms), displaying increased temporal dispersion
      (from 4.14+/-0.45 ms to 10.42+/-2.51 ms, both P<0.001), but was preserved in
      treated animals. Bosentan decreased norepinephrine, but increased epinephrine
      levels 24 h post-ligation. Low frequency spectra of heart rate variability, an
      index of net sympathetic tone, were lower in bosentan-treated rats. Dual
      endothelin-1 receptor blockade decreases ventricular tachyarrhythmias during
      myocardial infarction without reperfusion, by preventing repolarization
      inhomogeneity. Diverse treatment effects on sympathetic activation may ameliorate
      the antiarrhythmic action.

PMID- 18048028
TI  - Effect of GCP-02, a PPARalpha/gamma dual activator, on glucose and lipid
      metabolism in insulin-resistant mice.
AB  - This paper reports on the effect of GCP-02, a dual activator of the peroxisome
      proliferator-activated receptors alpha/gamma (PPARalpha/gamma), on glucose and
      lipid metabolism in insulin-resistant obese mice induced by monosodium glutamate.
      The mice were divided into four groups on the basis of treatment: control group,
      rosiglitazone (positive control) (7 micromol/kg), and low- and high-dosage GCP-02
      (7 micromol/kg and 3.5 micromol/kg, respectively). Drugs were given orally once a
      day for 19 days, and mice underwent testing for insulin tolerance, oral glucose
      tolerance and gluconeogenesis, and plasma cholesterol, triglyceride and free
      fatty acid levels. Mice were sacrificed, and body length and weight were
      measured; intraperitoneal adipose, heart and liver weighed; and plasma alanine
      aminotransferase (ALT) level and aspartate aminotransferase (AST) activity
      measured. Liver, soleus muscle and myocardium were assayed for glycogen,
      triglyceride and free fatty acid content and myocardia tested for superoxide
      dismutase (SOD) activity and malonaldehyde content. RT-PCR revealed expression of
      insulin receptor substrate 1 and 2 (IRS1, IRS2) and related genes in liver. GCP
      02 had a more powerful effect than rosiglitazone on improving insulin
      sensitivity, ameliorating glucose tolerance, suppressing L-alanine-induced
      gluconeogenesis, and decreasing plasma levels of cholesterol, triglyceride and
      free fatty acid. It reduced body weight in control mice, significantly lowered
      hepatic content of glycogen, triglyceride and free fatty acid and myocardial
      content of triglyceride, and increased myocardial SOD activity. IRS2 mRNA was
      down-regulated in control mice but up-regulated by GCP-02. Thus, GCP-02 is a
      potential candidate for the prevention and therapy of diseases associated with
      insulin resistance such as type 2 diabetes mellitus and cardiovascular disease.

PMID- 18048029
TI  - Chronic morphine treatment decreases the Cav1.3 subunit of the L-type calcium
      channel.
AB  - Voltage-gated L- and N-type calcium channels (VOCs) are implicated in the
      activity of morphine, but their contribution to the expression of opioid
      tolerance remains uncertain. L- and N-type VOCs are heteropentamers of alpha(1),
      alpha(2)delta, beta, and gamma subunits. The alpha(1) subunit forms both the ion
      pore and the binding site for ligands. The Ca(v)1.2 and Ca(v)1.3 are the neuronal
      dihydropyridine (DHP)-sensitive L-type channel subunit types. The Ca(v)2.2
      subunit is found in omega conotoxin GVIA-sensitive N-type calcium channels.
      Ca(v)1.2 VOC gating properties are phosphorylation-dependent with many kinases
      implicated. We hypothesized that changes in channel subunit structure or
      phosphorylation state, induced by chronic opioid exposure, may in part explain
      changes in calcium regulation observed both in vivo and in vitro. Antibodies,
      specific for the Ca(v)1.2, Ca(v)1.3, and Ca(v)2.2 subunits of VOCs were employed
      with Western immunoassays to access whether chronic morphine treatment had an
      effect on receptor protein levels. The L-type channel Ca(v)1.3 protein, but not
      the Ca(v)1.2 protein or phosphorylation state, significantly decreased upon
      chronic morphine treatment. The Ca(v)2.2 subunit protein of the N-type channel of
      VOCs remained unchanged. The Ca(v)1.3 subunit modification may represent one of
      many potential adaptive changes in tolerance to morphine-induced changes in
      intracellular calcium.

PMID- 18048031
TI  - Effects of sex, age, and season on plasma steroids in free-ranging Texas horned
      lizards (Phrynosoma cornutum).
AB  - The Texas horned lizard (Phrynosoma cornutum) is protected in several states due
      to its apparently declining numbers; information on its physiology is therefore
      of interest from both comparative endocrine and applied perspectives. We
      collected blood samples from free-ranging P. cornutum in Oklahoma from April to
      September 2005, spanning their complete active period. We determined plasma
      concentrations of the steroids, progesterone (P), testosterone (T), and
      corticosterone (CORT) by radioimmunoassay following chromatographic separation
      and 17beta-estradiol (E2) by direct radioimmunoassay. T concentrations in
      breeding males were significantly higher than in non-breeding males. P showed no
      significant seasonal variation within either sex. CORT was significantly higher
      during the egg-laying season compared to breeding and non-breeding seasons for
      adult females and it was marginally higher in breeding than in non-breeding males
      (P=0.055). CORT concentrations also significantly increased with handling in non
      breeding males and egg-laying females. Perhaps most surprisingly, there were no
      significant sex differences in plasma concentrations of P and E2. Furthermore,
      with respect to seasonal differences, plasma E2 concentrations were significantly
      higher in breeding females than in egg-laying or non-breeding females, and they
      were significantly higher in breeding than in non-breeding males. During the non
      breeding season, yearling males exhibited higher E2 concentrations than adult
      males; no other differences between the steroid concentrations of yearlings and
      adults were detected. In comparison to other vertebrates, the seasonal steroid
      profile of P. cornutum exhibited both expected and unexpected patterns, and our
      results illustrate the value of collecting such baseline data as a springboard
      for appropriate questions for future research.

PMID- 18048030
TI  - Benidipine, an anti-hypertensive drug, inhibits reactive oxygen species
      production in polymorphonuclear leukocytes and oxidative stress in salt-loaded
      stroke-prone spontaneously hypertensive rats.
AB  - Oxidative stress is associated with exacerbation of renal injuries in
      hypertension. In clinical studies benidipine hydrochloride (benidipine), a
      dihydropyridine calcium channel blocker with antioxidant activity, reduced
      oxidative stress. However, the mechanism of suppression of oxidative stress
      remains to be fully characterized. Reactive oxygen species production by
      polymorphonuclear leukocyte plays important pathological roles in hypertension.
      Therefore, we examined the effects of benidipine both on reactive oxygen species
      production of human polymorphonuclear leukocytes and oxidative stress of an
      animal model. Human peripheral polymorphonuclear leukocytes or polymorphonuclear
      leukocyte-like differentiated HL-60 cells were used to examine effects of
      benidipine (0.1-30 microM) on formyl-Met-Leu-Phe-induced reactive oxygen species
      production, calcium mobilization, NADPH oxidase activation and phosphorylation of
      protein kinase C substrates. High-salt (8% NaCl) loaded stroke-prone
      spontaneously hypertensive rats were treated with or without benidipine (1, 3, 10
      mg/kg/day) for 2 weeks, and thiobarbituric acid reactive substances, a plasma
      oxidative stress marker, and renal expression of oxidative stress-induced genes
      were measured. Benidipine concentration-dependently suppressed formyl-Met-Leu-Phe
      induced reactive oxygen species production in polymorphonuclear leukocytes more
      potently than other calcium channel blockers such as amlodipine, azelnidipine,
      nitrendipine and nifedipine. Benidipine partially inhibited all of intracellular
      Ca(2+) elevation, protein kinase C activation and NADPH oxidase activation. Salt
      loading in stroke-prone spontaneously hypertensive rats augmented plasma
      thiobarbituric acid reactive substances levels; renal dysfunction; and renal
      expression of transforming growth factor-beta, collagen I and collagen III mRNAs;
      which were attenuated by benidipine treatment. These results indicate that
      benidipine prevents the polymorphonuclear leukocyte-derived reactive oxygen
      species production, which is due at least in part to its antioxidant action and
      inhibition of Ca(2+)/protein kinase C/NADPH oxidase signaling. The attenuation of
      reactive oxygen species production might contribute to the drug's reduction of
      oxidative stress and renal injuries in hypertension.

PMID- 18048032
TI  - Surgical wound management.

PMID- 18048033
TI  - Necrotising fasciitis of upper and lower limb: a systematic review.
AB  - Necrotising fasciitis is a rapidly progressive, life threatening soft tissue
      infection. In a significant proportion of patients, the extremities are involved
      as a result of trauma, needle puncture or extravasation of drugs, often leading
      to limb loss and devastating disability. In this systematic review of necrotising
      fasciitis of the upper and lower extremities, we report on the clinical
      characteristics, the predisposing factors, the associated diseases, the
      pathogenic bacteria, the surgical treatment and the final outcome in terms of
      limb loss and mortality. Data for a total of 451 patients were analysed for each
      parameter of interest. A percentage of 22.3% of the reviewed patients underwent
      amputation or disarticulation of a limb following failure of multiple
      debridements to control infection and the mortality rate was estimated as high as
      21.9%.

PMID- 18048034
TI  - Role of biological modifiers regulating the immune response after trauma.
AB  - Trauma induces a profound immunological dysfunction. This is characterised by an
      early state of hyperinflammation, followed by a phase of immunosuppression with
      increased susceptibility to infection and multiple organ failure. Therapeutic
      strategies directed at restoring immune homeostasis after traumatic injuries have
      largely failed in translation from "bench to bedside". The present review
      illustrates the role of biological modifiers of the posttraumatic immune response
      by portraying different modalities of therapeutic immune modulation. The emphasis
      is placed on anti-inflammatory (steroids) and immune-stimulatory (interferon)
      pharmacological strategies and modified resuscitative strategies, as well as more
      unconventional immunomodulatory approaches, such as immunonutrition.

PMID- 18048035
TI  - Immunological reactions secondary to blood transfusion.
AB  - Multiply injured patients are at risk of developing the systemic inflammatory
      response syndrome, which may involve multiple organ failure, infections/sepsis,
      longer hospital stay and mortality. These systemic complications have been
      associated with immunological changes in which several components of the immune
      system have been implicated. Recent studies have shown that blood transfusions
      may increase these changes. The immunomodulating effects of packed red blood
      cells have been identified and attributed to contaminating leukocytes and
      inflammatory mediators in the supernatant liquid. This review will outline
      immunological consequences of allogeneic blood transfusion, with a special focus
      on trauma cases.

PMID- 18048036
TI  - Modulation of immune response by head injury.
AB  - Despite the fact that traumatic brain injury (TBI) is a silently growing
      epidemic, we are yet to understand its multifaceted pathogenesis, where various
      cellular pathways are initiated in response to both the primary mechanical insult
      and secondary physiologically mediated injury. Although the brain has
      traditionally been considered an immunologically privileged site, evidence to the
      contrary exists in studies of central nervous system (CNS) pathology, in
      particular TBI. Transmigration of leukocytes following blood brain barrier (BBB)
      disruption results in activation of resident cells of the CNS, such as microglia
      and astrocytes, to possess immunological function. Both infiltrating peripheral
      immune cells and activated resident cells subsequently engage in the intrathecal
      production of cytokines, important indicators of the presence of
      neuroinflammation. Cytokines can either promote this neurotoxicity, by
      encouraging excitotoxicity and propagating the inflammatory response, or
      attenuate the damage through neuroprotective and neurotrophic mechanisms,
      including the induction of cell growth factors. Certain cytokines perform both
      functions, for example, interleukin-6 (IL-6). This review article discusses the
      notion that the inflammatory response to TBI is no longer a peripherally mediated
      phenomenon, and that the CNS significantly influences the immunological sequence
      of events in the aftermath of injury.

PMID- 18048038
TI  - Assessment of the clinical course with inflammatory parameters.
AB  - Inflammatory changes after trauma depend on the severity and the distribution of
      the injury and can be modified by the medical treatment. They precede the
      development of organ dysfunction and may be used for monitoring purposes. Among
      these, pro-inflammatory cytokines appear to be the most reliable parameters.

PMID- 18048037
TI  - Trauma and immune response--effect of gender differences.
AB  - A major consequence of traumatic injury is immunosuppression. Findings from
      previous studies suggest that the depression of immune functions is severe in
      young males, ovariectomised and aged females. In contrast, the immune functions
      in proestrus females following trauma-haemorrhage are maintained. Studies have
      also shown that the survival rate in proestrus females following trauma
      haemorrhage and the induction of subsequent sepsis is significantly higher than
      in age-matched males and ovariectomised females. Furthermore, administration of
      female sex hormone 17beta-oestradiol in males and ovariectomised females after
      trauma-haemorrhage prevents the suppression of immune response. Thus, these
      findings suggest that sex hormones play a significant role in shaping the host
      response following trauma. This article reviews studies delineating the mechanism
      by which sex hormones regulate immune cell functions in the experimental model of
      trauma-haemorrhage. The findings from the studies reviewed in this article
      suggest that sex steroids can be synthesised by the immune cell. The findings
      further indicate that T cell and macrophages express receptors for androgen and
      oestrogen. Since these cells are also the cells that produce cytokines, local
      synthesis of active steroids in these cells may become the significant factor in
      modulating their cytokine production.

PMID- 18048039
TI  - Immunoparalysis after multiple trauma.
AB  - The immunological sequelae following multiple trauma constitute an ongoing
      challenge in critical care management. The overall immune response to multiple
      trauma is a multilevel complex interdependently involving neurohormonal, cellular
      and haemodynamic factors. Immunoparalysis is characterised by a reduced capacity
      to present antigens via downregulated HLA-DR and an unbalanced monocyte-T cell
      interaction. Trauma-induced death of functionally conducive immune cells in the
      early recovery phase is significant in the emergence of posttraumatic multiple
      organ dysfunction or failure. Novel findings may contribute to more appropriate
      immunomonitoring and improved treatment. We must consider the preservation and
      support of immune function as the ultimate therapeutic goal, which may override
      the current strategy of simply antagonising excessive pro- or anti-inflammatory
      immune responses of the severely injured person. This review focuses on the
      injury-induced conduct of key immune effector cells and associated effects
      promoting immunoparalysis after multiple trauma.

PMID- 18048040
TI  - Systemic inflammation after trauma.
AB  - Trauma is still one of the main reasons for death among the population worldwide.
      Mortality occurring early after injury is due to "first hits", including severe
      organ injury, hypoxia, hypovolaemia or head trauma. Massive injury leads to
      activation of the immune system and the early inflammatory immune response after
      trauma has been defined as systemic inflammatory response syndrome (SIRS).
      "Second hits" such as infections, ischaemia/reperfusion or operations can further
      augment the pro-inflammatory immune response and have been correlated with the
      high morbidity and mortality in the latter times after trauma. SIRS can lead to
      tissue destruction in organs not originally affected by the initial trauma with
      subsequent development of multi-organ dysfunction (MOD). The initial pro
      inflammatory response is followed by an anti-inflammatory response and can result
      in immune suppression with high risk of infection and sepsis. Trauma causes
      activation of nearly all components of the immune system. It activates the
      neuroendocrine system and local tissue destruction and accumulation of toxic
      byproducts of metabolic respiration leads to release of mediators. Extensive
      tissue injury may result in spillover of these mediators into the peripheral
      bloodstream to further maintain and augment the pro-inflammatory response.
      Hormones like ACTH, corticosteroids and catecholamines as well as cytokines,
      chemokines and alarmins play important roles in the initiation and persistence of
      the pro-inflammatory response after severe injury. The purpose of this review is
      therefore to describe the immunological events after trauma and to introduce
      important mediators and pathways of the inflammatory immune response.

PMID- 18048041
TI  - Complete unilateral absence of fallopian tube.

PMID- 18048042
TI  - Cervical LEEP margin status and post-LEEP Pap smear follow-up.

PMID- 18048043
TI  - Placental stem cell markers in pre-eclampsia.
AB  - OBJECTIVE: To investigate the placental CD34, CD44, and leukemia inhibitory
      factor (LIF) levels in normotensive and pre-eclamptic women. METHOD: The study
      population consisted of 21 women with pre-eclampsia. Twenty normotensive pregnant
      women served as controls and were matched to pre-eclamptic patients by
      gestational age at delivery. Decidual samples obtained from the central part of
      the placenta were stored at -70 degrees C until analysis. CD44 and LIF were
      quantified in homogenates by enzyme-linked immunosorbent assay (ELISA), while
      CD34 was quantified by flow cytometry. RESULTS: The pre-eclamptic and
      normotensive groups were well matched. There were no significant differences in
      age, parity, weight, and gestational age at birth between the groups (P>0.05).
      The mean placental levels of CD34 (6.55+/-2.48 vs 3.16+/-1.23), CD44 (385.24+/
      178.85 vs 157.75+/-31.73, and LIF (140+/-51.11 vs 96.25+/-31.62) were
      significantly higher in pre-eclamptic compared with normotensive women,
      respectively (P<0.05). CONCLUSION: Higher levels of CD34, CD44, and LIF were
      found in the placentas of pre-eclamptic compared with normotensive women.

PMID- 18048044
TI  - The silencing of cysteine proteases in Fasciola hepatica newly excysted juveniles
      using RNA interference reduces gut penetration.
AB  - Probing protein function in parasitic flatworms is hampered by the difficulties
      associated with the development of transgenic approaches. Although RNA
      interference (RNAi) in schistosomes shows much promise, it has not been reported
      in other trematodes. Here, we show the successful silencing of the cysteine
      proteases cathepsin B and L in the infective stage of Fasciola hepatica newly
      excysted juveniles (NEJs). Silencing resulted in marked reductions in target
      transcript levels and significant diminution in the encoded proteins in the gut.
      RNAi of either enzyme in NEJs induced transient, abnormal locomotory phenotypes,
      and significantly reduced penetration of the rat intestinal wall.

PMID- 18048045
TI  - Quantification of fenitrothion and its main metabolites in poplar leaves by
      isotope dilution gas chromatography-mass spectrometry coupled with solid-phase
      microextraction.
AB  - A sensitive and specific method for determining fenitrothion and its main
      metabolites, 3-methyl-4-nitrophenol and fenitrooxon, in poplar leaves using
      deuterated isotopes as the internal standard is described. The analytes and the
      labeled isotopes were extracted from leaves by solid-phase microextraction and
      subsequently analysed by gas chromatography coupled with mass spectrometry. The
      method had a chromatographic run time of 17.0 min and good linearity over the
      range 0.01-10 mg kg(-1). The detection limits ranged between 2.5 and 0.6 microg
      kg(-1). The isotopic dilution technique allowed improving significantly the
      repetitivity even using different fibers with the same coating (RSD<5.1%). The
      method was applied successfully to study the persistence of fenitrothion in
      forestal matrices in a poplar forest after cannon spray application of the
      insecticide.

PMID- 18048046
TI  - Liquid chromatographic determination of enrofloxacin in nasal secretions and
      plasma of healthy pigs using restricted access material for on-line sample clean
      up.
AB  - A new fully automated method was developed for the quantitative analysis of an
      antibacterial drug, enrofloxacin (ENRO), in both nasal secretions and plasma
      samples of healthy pigs. The method is based on the use of a pre-column packed
      with restricted access material (RAM), namely RP-18 ADS (alkyl diol silica), for
      on-line sample clean-up coupled to a liquid chromatographic (LC) column
      containing octadecyl silica. The only off-line sample preparation was the 50-fold
      dilution of nasal secretions and plasma samples in the washing liquid composed of
      25 mM phosphate buffer of pH 7.4. A 10 microl diluted sample volume was injected
      directly onto the pre-column and washed for 7 min. By rotation of a switching
      valve, the analyte of interest was eluted in the back-flush mode with the LC
      mobile phase which consisted in a mixture of 25 mM phosphate buffer of pH 3.0 and
      acetonitrile according to a segmented gradient elution. By a new rotation of the
      switching valve, the pre-column and the analytical column were equilibrated for 3
      min with the initial mobile phases. The flow-rate was 0.8 ml min(-1) for the
      washing liquid and 1.5 ml min(-1) for the LC mobile phase. ENRO was detected by
      fluorescence at excitation and emission wavelengths of 278 and 445 nm,
      respectively. Finally, the developed method was validated using an original
      strategy based on total measurement error and accuracy profiles as a decision
      tool. The limits of quantitation of ENRO in plasma and in nasal secretions were
      30.5 and 91.6 ng/ml, respectively. The validated method was then applied
      successfully to the determination of ENRO in healthy pigs treated by
      intramuscular injection at different doses (2.5, 10 and 30 mg/kg bodyweight) for
      a pilot study. This method could be also used for the simultaneous analysis of
      ENRO and its main metabolite, ciprofloxacin (CIPRO).

PMID- 18048048
TI  - Prediction of protein retention times in gradient hydrophobic interaction
      chromatographic systems.
AB  - A two-step methodology has been developed for the prediction of protein retention
      time in linear-gradient HIC systems. Isocratic retention parameters were
      determined from ln(k')-salt concentration plots for a number of commercially
      available proteins with a range of properties. Quantitative structure property
      relationship (QSPR) models based on a support vector machine (SVM) approach were
      generated for predicting isocratic retention parameters for proteins not included
      in the model generation. The predicted parameters were then used to calculate
      protein gradient retention times and the results indicate that this approach is
      well suited for predicting experimental gradient retention data. The approach
      presented in this paper may have implications for HIC methods development at both
      the bench and process scales.

PMID- 18048047
TI  - High-performance liquid chromatography enantioseparation of proton pump
      inhibitors using the immobilized amylose-based Chiralpak IA chiral stationary
      phase in normal-phase, polar organic and reversed-phase conditions.
AB  - The chiral resolving ability of the amylose-based Chiralpak IA chiral stationary
      phase towards omeprazole and other proton pump inhibitors under reversed-phase
      conditions was investigated. Organic modifier-buffer demonstrated to be a valid
      alternative elution mode with respect to conventional polar organic and normal
      phases. No evidence of deterioration of performance of the enantioselective
      column after several multimodal cycles of elution was observed. Mobile phase
      composition was systematically changed in order to modulate the enantiomer
      elution order of set of compounds studied. A very simple method based on on-line
      detection of optical rotational sign during enantioselective HPLC was developed
      to assign the absolute configuration and enantiomeric elution order.

PMID- 18048049
TI  - Co-electrospun SiO2 hollow nanostructured fibers with hierarchical walls.
AB  - SiO(2) hollow nanostructured fibers with hierarchical walls have been fabricated
      by the sol-gel combined two-capillary spinneret co-electrospinning technique
      using triblock copolymer as the porous directing agent. The as-prepared SiO(2)
      hollow nanostructured fibers were as long as 10 cm with the outer diameter of 400
      600 nm and shell thickness of 50-200 nm, and their walls contained the random
      mesopores with the size of 6.6 nm and the micropores with size of 0.6 nm based on
      the N(2) absorption-desorption isotherm.

PMID- 18048050
TI  - Water evaporation rates across hydrophobic acid monolayers at equilibrium
      spreading pressure.
AB  - The effect of alkanoic acid [CH(3)(CH(2))(n-2)COOH; HCn] and perfluoroalkanoic
      acid [CF(3)(CF(2))(n-2)COOH; FCn] monolayers on the water evaporation rate was
      investigated by thermogravimetry tracing the decrease in amount of water with
      time. The evaporation rate from the surface covered by a monolayer was measured
      as a function of temperature and hydrophobic chain length of the acids, where the
      monolayer was under an equilibrium spreading pressure. From thermal behavior of
      the crystallized acids, their solid states are C-type in crystalline state over
      the temperature range from 298.2 to 323.2 K. The dry air was flowed through a
      furnace tube of a thermogravimetry apparatus at the flow rate of 80 mL min(-1),
      where the evaporation rate becomes almost constant irrespective of the flow rate.
      The temperature dependence of the evaporation rate was analyzed kinetically to
      evaluate the activation energy and thermodynamics values for the activated
      complex, which demonstrated that these values were almost the same for both
      alkanoic acids and perfluoroalkanoic acids, although the effect of
      perfluoroalkanoic acids on the evaporation rate was smaller than that of
      corresponding hydrogenated fatty acids. The difference in the evaporation rate
      between FCn and HCn was examined by atomic force microscopy (AFM), Brewster angle
      microscopy (BAM), surface potential (DeltaV) at equilibrium spreading pressure,
      and Langmuir curve (pi-A isotherm), and their results were consistent and
      supported the difference.

PMID- 18048051
TI  - Histopathological features of ocular leishmaniosis in the dog.
AB  - Canine leishmaniosis (CL) can present with multiple clinical signs and ocular
      disease is reported to occur in almost 25% of affected dogs. The purpose of the
      present study was to characterize the nature of inflammation within the eyes of
      dogs with leishmaniosis and to determine whether parasites were present in these
      lesions. Eyes from 60 dogs with confirmed leishmaniosis that died or were
      humanely destroyed over a 4 year period were included in the study. Sections of
      formalin-fixed globes were stained with haematoxylin and eosin (HE) and subjected
      to immunohistochemistry using a Leishmania-specific antibody. Clinically evident
      ocular signs were present in 15 of 60 dogs (13 bilaterally and 2 unilaterally).
      Thirty-five of 60 dogs received some form of anti-protozoal treatment. In 36 of
      120 eyes (30%) a granulomatous inflammatory infiltrate was found and in 32 of 120
      eyes (26.6%) the parasite was identified immunohistochemically within the globe.
      Ocular tissues affected, in order of frequency, were conjunctiva and limbus,
      ciliary body, iris, cornea, sclera and iridocorneal angle, choroid and the optic
      nerve sheath. Different microscopical patterns were defined in each of these
      structures. Leishmania organisms and associated inflammation can be found in
      different ocular tissues, accounting for some of the ocular clinical signs
      described for this disease.

PMID- 18048052
TI  - Extraction and identification of electroimmunoprecipitated proteins from agarose
      gels.
AB  - A method for the identification of protein antigens captured in
      electroimmunoprecipitates was developed. Different antigen-antibody precipitates
      were generated by agarose gel immunoelectrophoresis. The immunoprecipitates were
      excised and various methods for extracting and dissociating the precipitates were
      systematically studied by analyzing for protein components of the extracts using
      peptide mass fingerprinting after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The optimal recovery of antigen was obtained by 24-h extraction
      at 37 degrees C using a minimal volume of 0.06 M Tris-HCl, 10% SDS (pH 7). This
      simple and robust method is useful for the characterization of antibody
      specificity. It can also be used to identify antigens generating unknown
      precipitates in crossed immunoelectrophoresis with polyspecific antisera,
      including human IgG-antigen complexes electroimmunoprecipitated by secondary
      antibodies. Thus, the method may prove useful as an additional technique in
      biomarker discovery.

PMID- 18048053
TI  - Infection by the microsporidium Vairimorpha necatrix (Microspora: Microsporidia)
      elevates juvenile hormone titres in larvae of the tomato moth, Lacanobia oleracea
      (Lepidoptera: Noctuidae).
AB  - The effects of infection by a microsporidium, Vairimorpha necatrix (Kramer), on
      the endogenous levels of juvenile hormones in tomato moth (Lacanobia oleracea L.)
      larvae were investigated. Levels of juvenile hormone II (JH II) were 10-fold
      greater in the infected larvae on day two of the sixth stadium but no significant
      difference was observed on day seven. Juvenile hormone I (JH I) was also detected
      in day two and day seven sixth instar infected larvae but was not detected in non
      infected larvae. The duration of the fifth and sixth stadia was significantly
      longer for infected larvae when compared with non-infected larvae. No evidence
      was found to suggest that supernumerary moults are a feature of infection by V.
      necatrix in L. oleracea larvae. Experiments were performed to determine whether
      the elevation in JH levels, which probably prevents pupation, is an adaptive
      mechanism of the microsporidium for extending the growth phase of the host,
      thereby allowing increased spore production. A proportion of infected larvae were
      collected on days 9 and 24 of the sixth stadium and spore extracts prepared from
      each larva. These days represent the average duration of the sixth stadium
      required for uninfected larvae to reach pupation, and the average number of days
      that V. necatrix-infected larvae survive in the sixth stadium before dying from
      infection. The mean spore yields from infected larvae 24 days into the sixth
      stadium were significantly higher than the spore yields obtained from day nine
      sixth instar larvae. The hypothesis that V. necatrix manipulates host
      endocrinology (i.e. prolong the host larval state to maximise spore yield) is
      discussed in context with the results obtained.

PMID- 18048054
TI  - Surface antigens of Xenorhabdus nematophila (F. Enterobacteriaceae) and Bacillus
      subtilis (F. Bacillaceae) react with antibacterial factors of Malacosoma disstria
      (C. Insecta: O. Lepidoptera) hemolymph.
AB  - Previous research established different interactions of the insect pathogen,
      Xenorhabdus nematophila and nonpathogen, Bacillus subtilis, with antimicrobial
      hemocytes and humoral factors of larval Malacosoma disstria [Giannoulis, P.,
      Brooks, C.L., Dunphy, G.B., Mandato, C.A., Niven, D.F., Zakarian, R.J., 2007.
      Interaction of the bacteria Xenorhabdus nematophila (Enterobacteriaceae) and
      Bacillus subtilis (Bacillaceae) with the hemocytes of larval Malacosoma disstria
      (Insecta: Lepidoptera: Lasicocampidae). J. Invertebr. Pathol. 94, 20-30]. The
      antimicrobial systems were inhibited by X. nematophila and stimulated by B.
      subtilis. The bacterial surface antigens participating in these reactions were
      unknown. Thus, herein the effects of lipopolysaccharide (endotoxin) from X.
      nematophila and lipoteichoic acid from B. subtilis on the larval M. disstria
      immune factors, the hemocytes and phenoloxidase, were determined. Endotoxin
      elevated the level of damaged hemocytes limiting the removal of X. nematophila
      from the hemolymph and enhancing the rapid release of bacteria trapped by
      nodulation. Similar effects were observed with the lipid A moiety of the
      endotoxin. The effects of lipopolysaccharide and lipid A on the hemocyte
      activities were abrogated by polymyxin B (an antibiotic that binds to lipid A)
      confirming lipopolysaccharide as the hemocytotoxin by virtue of the lipid A
      moiety. Lipoteichoic acid elicited nodulation and enhanced phenoloxidase
      activation and/or activity. Although lipoidal endotoxin and lipid A inhibited
      phenoloxidase activation they enhanced the activity of the enzyme. Apolipophorin
      III precluded the effects of lipopolysaccharide, lipid A, and lipoteichoic acid
      on the hemocytes and prophenoloxidase until the antigens exceeded a critical
      threshold.

PMID- 18048055
TI  - Calmodulin kinase II inhibition disrupts cardiomyopathic effects of enhanced
      green fluorescent protein.
AB  - Transgenic expression of enhanced green fluorescent protein (eGFP) in myocardium
      can result in cardiac dysfunction and cardiomyopathy, presumably through toxic
      effects that disrupt normal cellular signaling. The multifunctional Ca(2+)- and
      calmodulin-dependent protein kinase II (CaMKII) is widely expressed in myocardium
      and CaMKII activity is increased in human and animal models of cardiomyopathy, so
      we hypothesized that increased CaMKII activity is important for cardiomyopathy
      due to transgenic expression of eGFP. Here we report that cardiomyocyte-delimited
      eGFP over-expression causes increased CaMKII activity that predicts left
      ventricular dilation and dysfunction. On the other hand, transgenic co-expression
      of a CaMKII inhibitory peptide with eGFP prevents eGFP-mediated left ventricular
      dilation and dysfunction. These findings suggest that increased CaMKII activity
      is a critical pathological signal in transgenic cardiomyopathy due to eGFP over
      expression.

PMID- 18048056
TI  - NMR structure of the Escherichia coli type 1 pilus subunit FimF and its
      interactions with other pilus subunits.
AB  - Type 1 pili from uropathogenic Escherichia coli strains mediate bacterial
      attachment to target receptors on the host tissue. They are composed of up to
      3000 copies of the subunit FimA, which form the stiff, helical pilus rod, and the
      subunits FimF, FimG, and FimH, which form the linear tip fibrillum. All subunits
      in the pilus interact via donor strand complementation, in which the incomplete
      immunoglobulin-like fold of each subunit is complemented by insertion of an N
      terminal extension from the following subunit. We determined the NMR structure of
      a monomeric, self-complemented variant of FimF, FimF(F), which has a second FimF
      donor strand segment fused to its C-terminus that enables intramolecular
      complementation of the FimF fold. NMR studies on bimolecular complexes between
      FimF(F) and donor strand-depleted variants of FimF and FimG revealed that the
      relative orientations of neighboring domains in the tip fibrillum cover a wide
      range. The data provide strong support for the intrinsic flexibility of the tip
      fibrillum. They lend further support to the hypothesis that this flexibility
      would significantly increase the probability that the adhesin at the distal end
      of the fibrillum successfully targets host cell receptors.

PMID- 18048057
TI  - Characterization and further stabilization of designed ankyrin repeat proteins by
      combining molecular dynamics simulations and experiments.
AB  - Multiple molecular dynamics simulations with explicit solvent at room temperature
      and at 400 K were carried out to characterize designed ankyrin repeat (AR)
      proteins with full-consensus repeats. Using proteins with one to five repeats,
      the stability of the native structure was found to increase with the number of
      repeats. The C-terminal capping repeat, originating from the natural guanine
      adenine-binding protein, was observed to denature first in almost all high
      temperature simulations. Notably, a stable intermediate is found in experimental
      equilibrium unfolding studies of one of the simulated consensus proteins. On the
      basis of simulation results, this intermediate is interpreted to represent a
      conformation with a denatured C-terminal repeat. To validate this interpretation,
      constructs without C-terminal capping repeat were prepared and did not show this
      intermediate in equilibrium unfolding experiments. Conversely, the capping
      repeats were found to be essential for efficient folding in the cell and for
      avoiding aggregation, presumably because of their highly charged surface. To
      design a capping repeat conferring similar solubility properties yet even higher
      stability, eight point mutations adapting the C-cap to the consensus AR and
      adding a three-residue extension at the C-terminus were predicted in silico and
      validated experimentally. The in vitro full-consensus proteins were also compared
      with a previously published designed AR protein, E3_5, whose internal repeats
      show 80% identity in primary sequence. A detailed analysis of the simulations
      suggests that networks of salt bridges between beta-hairpins, as well as
      additional interrepeat hydrogen bonds, contribute to the extraordinary stability
      of the full consensus.

PMID- 18048058
TI  - The three-dimensional structure of genomic RNA in bacteriophage MS2: implications
      for assembly.
AB  - Using cryo-electron microscopy, single particle image processing and three
      dimensional reconstruction with icosahedral averaging, we have determined the
      three-dimensional solution structure of bacteriophage MS2 capsids reassembled
      from recombinant protein in the presence of short oligonucleotides. We have also
      significantly extended the resolution of the previously reported structure of the
      wild-type MS2 virion. The structures of recombinant MS2 capsids reveal clear
      density for bound RNA beneath the coat protein binding sites on the inner surface
      of the T=3 MS2 capsid, and show that a short extension of the minimal assembly
      initiation sequence that promotes an increase in the efficiency of assembly,
      interacts with the protein capsid forming a network of bound RNA. The structure
      of the wild-type MS2 virion at approximately 9 A resolution reveals icosahedrally
      ordered density encompassing approximately 90% of the single-stranded RNA genome.
      The genome in the wild-type virion is arranged as two concentric shells of
      density, connected along the 5-fold symmetry axes of the particle. This novel RNA
      fold provides new constraints for models of viral assembly.

PMID- 18048059
TI  - A pilot study to evaluate the effects of Cerebrolysin on cognition and qEEG in
      vascular dementia: cognitive improvement correlates with qEEG acceleration.
AB  - The effects of the neurotrophic compound Cerebrolysin (Cere) on cognitive
      performance, evaluated with the ADAS-cog, and on qEEG activity were investigated
      in forty one patients with mild to moderate severe probable vascular dementia
      (VaD) according to NINDS-AIREN criteria, included in a placebo-controlled pilot
      study. Patients received i.v. infusions of Cere (10 or 30 ml) or placebo (normal
      saline) 5 days/week for 4 weeks. Mean score of change from baseline in the ADAS
      cog and percent change from baseline in slow to fast EEG power ratio (PR) scores
      were the two primary endpoints. Correlations between cognition and qEEG were also
      evaluated for both baseline scores and for scores of change from baseline in ADAS
      cog and in qEEG parameters, including EEG power ratio (PR) as an index of EEG
      slowing. Baseline ADAS-cog scores showed significant positive correlations with
      delta power, theta power and PR scores, and correlated negatively with alpha
      activity. These correlations indicating that an increased EEG slowing is
      associated with a worst cognitive performance in VaD patients. Cere treatment
      improved cognitive performance significantly at the 10 ml dose and reduced EEG
      slowing with both 10 and 30 ml dosages. A significant positive correlation
      between PR and ADAS-cog scores of change from baseline was observed in Cere
      treated patients. According to results of this pilot study, it is concluded that
      Cere improves cognitive performance and reduces EEG slowing in patients with VaD,
      and that there is a positive relationship between changes in cognition and qEEG
      activity induced by Cere. The conduction of further regular clinical trials is
      required to confirm the potential utility of Cere in the treatment of VaD
      suggested by the present results.

PMID- 18048060
TI  - Insulin modulates norepinephrine-mediated melatonin synthesis in cultured rat
      pineal gland.
AB  - The mammalian pineal gland synthesizes melatonin in a circadian manner, peaking
      during the dark phase. This synthesis is primarily regulated by sympathetic
      innervations via noradrenergic fibers, but is also modulated by many peptidergic
      and hormonal systems. A growing number of studies reveal a complex role for
      melatonin in influencing various physiological processes, including modulation of
      insulin secretion and action. In contrast, a role for insulin as a modulator of
      melatonin synthesis has not been investigated previously. The aim of the current
      study was to determine whether insulin modulates norepinephrine (NE)-mediated
      melatonin synthesis. The results demonstrate that insulin (10(- 8)M) potentiated
      norepinephrine-mediated melatonin synthesis and tryptophan hydroxylase (TPOH)
      activity in ex vivo incubated pineal glands. When ex vivo incubated pineal glands
      were synchronized (12h NE-stimulation, followed by 12h incubation in the absence
      of NE), insulin potentiated NE-mediated melatonin synthesis and arylalkylamine-N
      acetyltransferase (AANAT) activity. Insulin did not affect the activity of
      hydroxyindole-O-methyltranferase (HIOMT), nor the gene expression of tpoh, aanat,
      or hiomt, under any of the conditions investigated. We conclude that insulin
      potentiates NE-mediated melatonin synthesis in cultured rat pineal gland,
      potentially through post-transcriptional events.

PMID- 18048061
TI  - Angiotensin II mimics the hypoxic effect on regulating trophoblast proliferation
      and differentiation in human placental explant cultures.
AB  - Regulation of cytotrophoblast differentiation toward extravillous trophoblasts
      (EVTs) is critical for establishing successful pregnancy. Previous studies have
      focused primarily on the factors promoting the differentiation, while inhibitory
      regulators except hypoxia have been less documented. In this study, to test our
      hypothesis that angiotensin II (Ang II) would inhibit EVT differentiation, we
      investigated the effects of Ang II on trophoblast outgrowth and the expression of
      molecules associated with the proliferation and invasion of trophoblasts using
      human first trimester villous explant cultures. Ang II increased EVT outgrowth
      and the number of cells in cell columns. Moreover, Ang II-treated explants
      exhibited increased Ki67 and integrin alpha5 immunoreactivity in EVTs as well as
      matrix metalloproteinase-2 activity in the conditioned media, and decreased
      alpha1 integrin immunoreactivity, which are compatible with the features of the
      proliferative phenotype EVTs. These effects of Ang II were similar to those of
      hypoxia (3% O(2)). Ang II stimulated the expression of hypoxia inducible factor
      1alpha at both mRNA and protein levels, and also enhanced the expression of
      plasminogen activator inhibitor-1 (PAI-1). Data presented herein suggest a
      possible role for Ang II in impairing trophoblast differentiation toward an
      invasive phenotype, which might be associated with shallow invasion in
      preeclamptic placentas.

PMID- 18048062
TI  - In vitro and in vivo neuroprotective effect and mechanisms of glabridin, a major
      active isoflavan from Glycyrrhiza glabra (licorice).
AB  - Stroke is a life-threatening disease characterized by rapidly developing clinical
      signs of focal or global disturbance of cerebral function due to cerebral
      ischemia. A number of flavonoids have been shown to attenuate the cerebral
      injuries in stroked animal models. Glabridin, a major flavonoid of Glycyrrhiza
      glabra (licorice), possesses multiple pharmacological activities. This study
      aimed to investigate whether glabridin modulated the cerebral injuries induced by
      middle cerebral artery occlusion (MCAO) in rats and staurosporine-induced damage
      in cultured rat cortical neurons and the possible mechanisms involved. Our study
      showed that glabridin at 25mg/kg by intraperitoneal injection, but not at 5mg/kg,
      significantly decreased the focal infarct volume, cerebral histological damage
      and apoptosis in MCAO rats compared to sham-operated rats. Glabridin
      significantly attenuated the level of brain malonyldialdehyde (MDA) in MCAO rats,
      while it elevated the level of two endogenous antioxidants in the brain, i.e.
      superoxide dismutase (SOD) and reduced glutathione (GSH). Co-treatment with
      glabridin significantly inhibited the staurosporine-induced cytotoxicity and
      apoptosis of cultured rat cortical neurons in a concentration-dependent manner.
      Consistently, glabridin significantly reduced the DNA laddering caused by
      staurosporine in a concentration-dependent manner. Glabridin also suppressed the
      elevated Bax protein and caspase-3 proenzyme and decreased bcl-2 induced by
      staurosporine in cultured rat cortical neurons, facilitating cell survival.
      Glabridin also inhibited superoxide production in cultured cortical neurons
      exposed to staurosporine. These findings indicated that glabridin had a
      neuroprotective effect via modulation of multiple pathways associated with
      apoptosis. Further studies are warranted to further investigate the biochemical
      mechanisms for the protective effect of glabridin on neurons and the evidence for
      clinical use of licorice in the management of cerebral ischemia.

PMID- 18048063
TI  - Phytoremediation of shallow organically enriched marine sediments using benthic
      microalgae.
AB  - We examined whether replantation of benthic microalgae (BMA) can remediate
      shallow organically enriched sediment. Nitzschia sp., the dominant species in the
      tested area (Hiroshima Bay, Japan), was isolated and mass cultured, then
      replanted in the same area. Changes in the condition of the sediment were
      monitored for five months. During the study period, we observed an increase in
      redox potential (ORP) and a decrease in acid-volatile sulfide (AVS) in the
      experimental area, indicating that the sediment condition changed from reduced to
      oxic. Organic matter in the sediment, represented by chemical oxygen demand
      (COD), ignition loss (IL) and organic nitrogen (ON) decreased significantly,
      while inorganic nutrients (ammonia and phosphate) increased in the interstitial
      water. These changes imply that oxygen produced by the replanted BMA may have
      enhanced aerobic bacterial activity, accelerating the decomposition of organic
      matter. Thus, replantation of BMA shows potential as a novel and promising
      "phytoremediation" method for organically enriched sediment.

PMID- 18048064
TI  - The importance of the intensity and frequency of perturbations on the germination
      delay.
AB  - An iterative model is developed to evaluate the reproductive strategies of plants
      in environments with different frequencies and intensities of disturbance. Two
      extreme reproductive strategies are compared: the "homocarpic" strategy, in which
      all the seeds germinate the following spring, without dormancy, and the
      "heterocarpic" strategy, whereby, each year, half of the existing seeds
      germinate. It is observed that this sort of heterocarpy is beneficial in
      environments with strong perturbations, in which a high percentage of the
      population dies. However, the frequency of such perturbations does not cause
      changes in the advantage of one strategy over the other. The results suggest that
      the intensity of the disturbance is much more important than the frequency.

PMID- 18048065
TI  - Synchronized dynamics and non-equilibrium steady states in a stochastic yeast
      cell-cycle network.
AB  - Applying the mathematical circulation theory of Markov chains, we investigate the
      synchronized stochastic dynamics of a discrete network model of yeast cell-cycle
      regulation where stochasticity has been kept rather than being averaged out. By
      comparing the network dynamics of the stochastic model with its corresponding
      deterministic network counterpart, we show that the synchronized dynamics can be
      soundly characterized by a dominant circulation in the stochastic model, which is
      the natural generalization of the deterministic limit cycle in the deterministic
      system. Moreover, the period of the main peak in the power spectrum, which is in
      common use to characterize the synchronized dynamics, perfectly corresponds to
      the number of states in the main cycle with dominant circulation. Such a large
      separation in the magnitude of the circulations, between a dominant, main cycle
      and the rest, gives rise to the stochastic synchronization phenomenon.

PMID- 18048066
TI  - Hypoxanthine uptake and release by equilibrative nucleoside transporter 2 (ENT2)
      of rat microvascular endothelial cells.
AB  - The cardioprotective actions of adenosine are terminated by its uptake into
      endothelial cells with subsequent metabolism through hypoxanthine to uric acid.
      This process involves xanthine oxidase-mediated generation of reactive oxygen
      species (ROS), which have been implicated in the vascular dysfunction observed in
      ischemia-reperfusion injury. The equilibrative nucleoside transporter, ENT2,
      mediates the transfer of hypoxanthine into cells. We hypothesize that ENT2 also
      mediates the cellular release of hypoxanthine, which would limit the amount of
      intracellular hypoxanthine available for xanthine oxidase-mediated ROS
      production. Rat microvascular endothelial cells (MVECs) were isolated from
      skeletal muscle by lectin-affinity purification. The transport of
      [(3)H]hypoxanthine was assessed using an oil-stop method, and hypoxanthine
      metabolites were identified by thin-layer chromatography. MVECs accumulated
      hypoxanthine with a K(m) of 300 microM and a V(max) of 2.8 pmol microl(-1) s(-1).
      ATP-depleted cells loaded with [(3)H]hypoxanthine released the radiolabel with
      kinetics similar to that obtained for [(3)H]hypoxanthine influx. The uptake and
      release of [(3)H]hypoxanthine were both blocked by ENT2 inhibitors with similar
      order of potency. Thus, ENT2 mediates both the influx and efflux of hypoxanthine.
      Inhibition of ENT2 in MVECs might be expected to increase the amount of
      intracellular hypoxanthine available for metabolism by xanthine oxidase and
      enhance the intracellular production of ROS.

PMID- 18048068
TI  - The differential regulation of BDNF and TrkB levels in juvenile rats after four
      days of escitalopram and desipramine treatment.
AB  - Major depressive disorder is a major health problem in adults and is now
      recognized as a substantial problem in children as well. Tricyclic
      antidepressants, including desipramine (DMI), are no better than placebo in
      treating childhood and adolescent depression, but are effective in treating adult
      depression. Several studies have suggested that normal BDNF (brain-derived
      neurotrophic factor) signaling is necessary for antidepressant drug action.
      Antidepressant drugs induce several plastic changes in the rodent brain which may
      be associated with changes in BDNF levels and/or with BDNF function. In the
      present study we report parallel measurements of BDNF mRNA and protein in the
      frontal cortex and hippocampus after four days of twice daily treatments with
      escitalopram, a selective serotonin reuptake inhibitor, and desipramine, a
      tricyclic antidepressant. Post-natal day 13, 21, 28 and adult rats were used in
      this study. TrkB (the primary receptor for BDNF) mRNA levels were also examined
      under the same treatment conditions. BDNF mRNA and protein levels, as well as
      TrkB mRNA levels, were increased significantly in post-natal day 13 pups after
      escitalopram treatment as compared to control, but desipramine failed to increase
      either BDNF or TrkB. The failure of desipramine to increase BDNF and TrkB levels
      in juvenile rats is consistent with the lack of efficacy of desipramine in
      children and adolescents. The serotonergic nervous system matures earlier than
      the noradrenergic system, which may explain why escitalopram, but not
      desipramine, increases BDNF and TrkB levels.

PMID- 18048067
TI  - Human postmortem brain-derived cerebrovascular smooth muscle cells express all
      genes of the classical complement pathway: a potential mechanism for vascular
      damage in cerebral amyloid angiopathy and Alzheimer's disease.
AB  - Deposition of amyloid around blood vessels, known as cerebral amyloid angiopathy
      (CAA), is a major pathological feature found in the majority of Alzheimer's
      disease (AD) cases, and activated complement fragments have been detected on CAA
      deposits in AD brains. In this study, we demonstrate for the first time that
      human cerebrovascular smooth muscle cells (HCSMC) isolated from cortical vessels
      derived from postmortem brains can express mRNAs for complement genes C1qB, C1r,
      C1s, C2, C3, C4, C5, C6, C7, C8 and C9, the components of the classical
      complement pathway. Secretion of the corresponding complement proteins for these
      genes was also demonstrated, except for C1q and C5. Of particular significance
      was the observation that treatment of HCSMC with aggregated amyloid beta (Abeta)
      1-42 increased expression of complement C3 mRNA and increased release of C3
      protein. Abeta treatment of HCSMC also increased expression of C6 mRNA.
      Interferon-gamma induced expression and release of complement C1r, C1s, C2 and
      C4. As HCSMC are closely associated with Abeta deposits in vessels in the brain,
      their production of complement proteins could amplify the proinflammatory effects
      of amyloid in the perivascular environment, further compromising brain vascular
      integrity.

PMID- 18048069
TI  - Alkaloids and saponins from blue cohosh.
AB  - Blue cohosh, Caulophyllum thalictroides (L.) Michx. (Berberidaceae), is used
      primarily to cure menstrual disturbances and to ease childbirth. Alkaloids and
      saponins are considered to be responsible for its pharmacological activity. A
      detailed phytochemical investigation of blue cohosh resulted in the isolation of
      15 compounds belonging to the alkaloids and the triterpene saponins. The
      structures of two alkaloids, caulophyllumines A (1) and B (2) and a saponin,
      cauloside H (3) both previously unknown were determined by spectroscopic
      techniques, including by 1- and 2-D NMR as well as by chemical analysis.

PMID- 18048070
TI  - An in-host model of acute infection: measles as a case study.
AB  - The epidemiology of acute infections is strongly influenced by the immune status
      of individuals. In-host models can provide quantitative predictions of immune
      status and can thus offer valuable insights into the factors that influence
      transmission between individuals and the effectiveness of vaccination protocols
      with respect to individual immunity. Here we develop an in-host model of measles
      infection. The model explicitly considers the effects of immune system memory and
      CD8 T-cells, which are key to measles clearance. The model is used to determine
      the effects of waning immunity through vaccination and infection, the effects of
      booster exposures or vaccines on the level of immunity, and the immune system
      characteristics that result in measles transmission (R(0)>1) even if an
      individual has no apparent clinical symptoms. We find that the level of immune
      system CD8 T-cells at the time of exposure to measles determines whether an
      individual will experience a measles infection or simply a boost in immunity. We
      also find that the infected cell dynamics are a good indicator of measles
      transmission and the degree of symptoms that will be experienced. Our results
      indicate that the degree of immunity in adults is independent of the source of
      exposure in early childhood, be it vaccine or natural infection.

PMID- 18048071
TI  - Ligand-dependent interactions of the Ah receptor with coactivators in a mammalian
      two-hybrid assay.
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a high affinity ligand for the aryl
      hydrocarbon receptor (AhR). In this study, we investigated structure-dependent
      differences in activation of the AhR by a series of halogenated aromatic
      hydrocarbons. TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,7,8
      tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and
      3,3',4,4',5-pentachlorobiphenyl (PCB126) induced CYP1A1-dependent activities in
      HEK293 human embryonic kidney, Panc1 pancreatic cancer, and Hepa1c1c7 mouse
      hepatoma cell lines. There was a structure-dependent difference in the efficacy
      of TCDF and PCB126 in HEK293 and Panc1 cells since induced CYP1A1 mRNA levels
      were lower than observed for the other congeners. A mammalian two-hybrid assay in
      cells transfected with GAL4-coactivator and AhR-VP16 chimeras was used to
      investigate structure-dependent interactions of these chimeras in Panc1, HEK293,
      and Hepa1c1c7 cells. The reporter construct pGAL4-luc contains five tandem GAL4
      response elements linked to the luciferase gene and the GAL4-coactivator chimeras
      express several coactivators including steroid receptor coactivator 1 (SRC-1),
      SRC-2 and SRC-3, the mediator coactivator TRAP220, coactivator associated
      arginine methyl transferase 1 (CARM-1), and peroxisome proliferator-activated
      receptor gamma coactivator 1 (PGC-1). Results of the mammalian two-hybrid studies
      clearly demonstrate that activation of pGAL4-luc in cells transfected with VP-AhR
      and GAL4-coactivator chimeras is dependent on the structure of the HAH congener,
      cell context, and coactivator, suggesting that the prototypical HAH congeners
      used in this study exhibit selective AhR modulator activity.

PMID- 18048072
TI  - Inhibition of the adenine nucleotide translocator by N-acetyl perfluorooctane
      sulfonamides in vitro.
AB  - N-alkyl perfluorooctane sulfonamides have been widely used as surfactants on
      fabrics and papers, fire retardants, and anti-corrosion agents, among many other
      commercial applications. The global distribution and environmental persistence of
      these compounds has generated considerable interest regarding potential toxic
      effects. We have previously reported that perfluorooctanesulfonamidoacetate
      (FOSAA) and N-ethylperfluorooctanesulfonamidoacetate (N-EtFOSAA) induce the
      mitochondrial permeability transition (MPT) in vitro. In this study we tested the
      hypothesis that FOSAA and N-EtFOSAA interact with the adenine nucleotide
      translocator (ANT) resulting in a functional inhibition of the translocator and
      induction of the MPT. Respiration and membrane potential of freshly isolated
      liver mitochondria from Sprague-Dawley rats were measured using an oxygen
      electrode and a tetraphenylphosphonium-selective (TPP(+)) electrode,
      respectively. Mitochondrial swelling was measured spectrophotometrically. The ANT
      ligands bongkregkic acid (BKA) and carboxyatractyloside (cATR) inhibited
      uncoupling of mitochondrial respiration caused by 10 microM N-EtFOSAA, 40 microM
      FOSAA, and the positive control 8 microM oleic acid. ADP-stimulated respiration
      and depolarization of mitochondrial membrane potential were inhibited by cATR,
      FOSAA, N-EtFOSAA, and oleic acid, but not by FCCP. BKA inhibited calcium
      dependent mitochondrial swelling induced by FOSAA, N-EtFOSAA, and oleic acid.
      Seventy-five micromolar ADP also inhibited swelling induced by the test
      compounds, but cATR induced swelling was not inhibited by ADP. Results of this
      investigation indicate that N-acetyl perfluorooctane sulfonamides interact
      directly with the ANT to inhibit ADP translocation and induce the MPT, one or
      both of which may account for the metabolic dysfunction observed in vivo.

PMID- 18048073
TI  - Central role of mitochondria and p53 in PUVA-induced apoptosis in human
      keratinocytes cell line NCTC-2544.
AB  - Despite strong evidence concerning the high efficiency of PUVA therapy (psoralen
      plus UVA light), its mechanism of action has not yet been fully elucidated. In
      this study, we have evaluated in a cell line of human keratinocytes (NCTC-2544)
      the effects of two linear psoralen derivatives, 8-methoxypsoralen (8-MOP) and 5
      methoxypsoralen (5-MOP), that are widely used in PUVA therapy and two angular
      derivatives, Angelicin (ANG) and 4,6,4'-trymetyl angelicin (TMA). All derivatives
      photoinduce cellular death, TMA being the most active compound. The cell cycle
      analysis showed that the four derivatives induce, 24 h after irradiation, a cell
      cycle arrest in G1 phase later followed by massive apoptosis. The G1 arrest is
      correlated to an increase in the expression of p21(Waf1/Cip1), a protein
      associated with the cell cycle block and apoptosis. Furthermore, treatment of
      NCTC-2544 resulted in p53 activation by 5-MOP, 8-MOP, and ANG but not TMA and its
      phosphorylation at serine-15. The levels of p21(Waf1/Cip1) paralleled p53 protein
      staining pattern suggesting that p53 activation correlated with p21(Waf1/Cip1)
      induction. Simultaneous to p53 activation, psoralens induced mitochondrial
      depolarization, cytochrome c release, mitochondrial production of reactive oxygen
      species, as well as caspase-3 and -9 activation. Thus these results strongly
      indicate the necessity of p53 activation and the induction of the apoptotic
      machinery downstream of mitochondria.

PMID- 18048074
TI  - Enhanced cell surface expression, immunogenicity and genetic stability resulting
      from a spontaneous truncation of HIV Env expressed by a recombinant MVA.
AB  - During propagation of modified vaccinia virus Ankara (MVA) encoding HIV 89.6 Env,
      a few viral foci stained very prominently. Virus cloned from such foci replicated
      to higher titers than the parent and displayed enhanced genetic stability on
      passage. Sequence analysis showed a single nucleotide deletion in the 89.6 env
      gene of the mutant that caused a frame shift and truncation of 115 amino acids
      from the cytoplasmic domain. The truncated Env was more highly expressed on the
      cell surface, induced higher antibody responses than the full-length Env, reacted
      with HIV neutralizing monoclonal antibodies and mediated CD4/co-receptor
      dependent fusion. Intramuscular (i.m.), intradermal (i.d.) needleless, and
      intrarectal (i.r.) catheter inoculations gave comparable serum IgG responses.
      However, intraoral (i.o.) needleless injector route gave the highest IgA in lung
      washings and i.r. gave the highest IgA and IgG responses in fecal extracts.
      Induction of CTL responses in the spleens of individual mice as assayed by
      intracellular cytokine staining was similar with both the full-length and
      truncated Env constructs. Induction of acute and memory CTL in the spleens of
      mice immunized with the truncated Env construct by i.d., i.o., and i.r. routes
      was comparable and higher than by the i.m. route, but only the i.r. route induced
      CTL in the gut-associated lymphoid tissue. Thus, truncation of Env enhanced
      genetic stability as well as serum and mucosal antibody responses, suggesting the
      desirability of a similar modification in MVA-based candidate HIV vaccines.

PMID- 18048075
TI  - Conversion of secondary pulp/paper sludge powder to liquid oil products for
      energy recovery by direct liquefaction in hot-compressed water.
AB  - The present work demonstrated that secondary pulp/paper sludge powder, with a
      higher heating value of 18.3MJ/kg on a dry basis, could be effectively converted
      into liquid oil products by direct liquefaction in hot-compressed water with and
      without catalyst. Treatments of secondary pulp/paper sludge in water at 250-380
      degrees C for 15-120min in the presence of N(2) atmosphere resulted in yields of
      water-soluble oils at 20-45wt% and yields of heavy oils at 15-25wt%, with higher
      heating values of 10-15 and >35MJ/kg, respectively. The higher caloric values for
      the heavy oil products were accounted for by their compositions of long-chain
      carboxylic acids, heterocyclic nitrogen compounds and phenolic compounds and
      derivatives as evidenced by the gas chromatograph (GC)/MS measurements. The
      liquefaction product yields were significantly influenced by the liquefaction
      temperature, the residence time, the initial biomass concentration, catalysts and
      the liquefaction atmosphere (inert or reducing). Within the temperature range
      (250-380 degrees C) tested, the lowest temperature produced the highest yield of
      total oils (at 60wt%), while the greatest yield of heavy oil (at about 24wt%) was
      obtained at 350 degrees C. If the temperature was fixed at 280 degrees C, a
      greater yield of heavy oil (reaching as high as 25wt% for 120min) was obtained as
      the length of reaction time increased. Similarly, a higher initial biomass
      concentration produced a greater yield of heavy oil but a reduced yield of water
      soluble oil. The presence of 0.1M K(2)CO(3) dramatically enhanced organic
      conversion, but suppressed the formation of both heavy oil and water-soluble oil.
      The use of the two alkaline earth metal catalysts, i.e., Ca(OH)(2) and Ba(OH)(2),
      did not alter organic conversion, but it catalyzed the formation of water-soluble
      oil and produced higher yields of total oil products. It was also demonstrated
      that the reducing atmosphere (i.e., H(2)) in the liquefaction process promoted
      the heavy oil formation while suppressing the water-soluble oil formation. With
      the presence of 0.1M Ca(OH)(2) and 2MPa H(2), liquefaction of the sludge powder
      in water at 280 degrees C for 60min produced a higher yield of heavy oil (26wt%),
      almost two times as high as that in N(2) (13.6wt%), resulting in a greater net
      energy efficiency. It was thus suggested that direct liquefaction of secondary
      pulp/paper sludge in hot-compressed water with Ca(OH)(2) catalyst and in the
      presence of H(2) could be an effective approach to recovering energy from the
      waste for production of liquid oil products.

PMID- 18048076
TI  - Comparative study of ozonation and synthetic goethite-catalyzed ozonation of
      individual NOM fractions isolated and fractionated from a filtered river water.
AB  - This study comparatively investigated ozonation and synthetic goethite-catalyzed
      ozonation of individual natural organic matter (NOM) fractions in terms of ozone
      consumption, dissolved organic carbon (DOC) and UV-absorbance reduction,
      molecular weight (MW) distribution, and formation of low-MW oxidation by
      products. Hydrophobic acid and neutral (HOA and HON) and hydrophilic acid and
      base (HIA and HIB) were four major NOM fractions isolated from a filtered river
      water; so ozonation and catalytic ozonation were carried out on these fractions.
      Results indicate that in comparison to ozonation alone, catalytic ozonation can
      enhance ozone consumption, UV(254) and DOC reduction, fragmentation of fraction
      components with MW>3000Da, and formation of oxalic acid for these fractions under
      normal reaction conditions commonly adopted in water treatment plants. In
      addition, catalytic ozonation can enhance aldehydes formation and increase the
      percentage of easy biodegradable organic carbon compared with ozonation alone for
      HIA and HIB, but exert much less effect on these items for HOA and HON.

PMID- 18048077
TI  - Effects of chlorine on organophosphorus pesticides adsorbed on activated carbon:
      desorption and oxon formation.
AB  - We investigated effects of chlorination on four organophosphorus pesticides
      (diazinon, isoxathion, malathion, and tolclofos-methyl) adsorbed on powdered
      activated carbon (PAC). Following adsorption of each pesticide on 10mg/L of PAC
      in water, chlorine was added. After 30min of chlorination, the corresponding
      oxons were detected in the water, but the parent compounds were not detected.
      Molar ratios of the oxon concentration in solution after 30min of chlorine
      addition to the initial pesticide concentration before the adsorption process
      were 4.1% and 7.9% for diazinon, 3.9% and 5.8% for isoxathion, 1.2% and 1.7% for
      malathion, and 1.4% and 1.4% for tolchlofos-methyl, in the case of 2 and 5mg/L of
      chlorine addition. The results suggested that the oxons were desorbed from the
      PAC by chlorination. The concentrations of the desorbed oxons gradually decreased
      with time, apparently owing to their readsorption by the PAC. Results from
      additional experiments suggest the following sequence of events: (i) adsorbed
      pesticides are oxidized by chlorine on the surface of the PAC and transformed
      into corresponding oxons; (ii) the oxons are released from the PAC; (iii) the
      released oxons are gradually readsorbed by the PAC, decreasing their
      concentrations in the water phase.

PMID- 18048078
TI  - Modeling simultaneous autotrophic and heterotrophic growth in aerobic granules.
AB  - A mathematical model has been developed to describe the simultaneous autotrophic
      and heterotrophic growth in granule-based sequencing batch reactors (SBRs).
      Experimental results of a laboratory-scale granule-based SBR are used to
      calibrate and validate the model. The model is able to simulate the reactor
      performance and gain insight in autotrophic and heterotrophic growth in the
      granules. With the established model, the fractions of active biomass (autotrophs
      and heterotrophs) and inert biomass are predicted to be 55.6% and 44.4% of the
      total mixed liquid volatile suspended solid, respectively, at a solids retention
      time (SRT) of 20 days. Biomass content increases with increasing SRT, but active
      biomass ratio decreases. Autotrophs have no significant effect on the total
      biomass content, although they play an important role in nitrogen removal.
      Simulation results also demonstrate the key role of the influent substrate and
      NH(4)(+)-N in governing the composition of heterotrophic and autotrophic biomass
      in a granule-based SBR. The autotrophs are mainly located on the outer layer of
      granules, whereas the heterotrophs are present in the center of granules, or on
      the outer layer of granules.

PMID- 18048079
TI  - Occurrence and fate of endocrine disrupters in Greek sewage treatment plants.
AB  - The occurrence of five endocrine-disrupting compounds (EDCs), namely 4-n
      nonylphenol (4-n-NP), nonylphenol monoethoxylate (NP1EO), nonylphenol
      diethoxylate (NP2EO), triclosan (TCS) and bisphenol A (BPA), was assessed in the
      raw, treated wastewater and sewage sludge of eight sewage treatment plants (STPs)
      in Greece. The analytes were extracted by solid-phase extraction (dissolved
      phase) or sonication (solid phase). Qualitative and quantitative analyses were
      performed by gas chromatography-mass spectrometry (GC-MS). The average
      concentrations in the raw and treated wastewater ranged from 0.23 (4-n-NP) to
      5.76microgL(-1) (NP1EO) and from 0.15 (BPA) to 1.84microgL(-1) (NP2EO),
      respectively. A great part of the detected EDCs was sorbed on suspended solids.
      In sewage sludge, the average concentrations ranged between 0.17 (4-n-NP) and
      12.3microgg(-1)dw (NP1EO). Analysis of daily mass flows in STP of Athens showed
      that, with the exception of 4-n-NP, all other EDCs were significantly removed
      (>85%) during wastewater treatment. Regarding the fate of these compounds, a
      significant part ranging from 45% (for TCS) to more than 70% (for NP1EO, NP2EO
      and BPA) was transformed by abiotic or biotic mechanisms, while the rest was
      accumulated in sewage sludge or disposed to the environment via the effluents.
      Calculation of risk quotients showed the existence of possible threat due to the
      presence of certain EDCs in treated wastewater and sludge.

PMID- 18048080
TI  - The differences in phenolic content in rivers exposed and non-exposed to
      anthropogenic contamination.
AB  - The purpose of the work was to determine the differences in a kind, number and
      concentrations of phenol, chlorophenols, chlorocatechols chlorinated
      methoxyphenols (chloroguaiacols, chlorosyringols) and 3,4,5-trichloroveratrole in
      the drainage of the Dzierzazna river, the flow non-exposed to anthropogenic
      contamination and in the Ner river, the flow exposed to anthropogenic pollution.
      The samples of water were collected in the Dzierzazna river in the Swoboda
      locality, the inflow of the Dzierzazna river - the Ciosenka river and, also, in
      the spring situated in Ciosny Sady locality. Water of the Ner river was collected
      in points near Lodz, Konstantynow, Poddebice and Dabie towns. The compounds were
      condensed (adsorbed) and eluted with methylene chloride on octadecyl C18 layer in
      a Baker Separex system. The obtained eluent was separated using the method of gas
      chromatography and analysed using mass spectrometry technique. In samples
      collected from the drainage of the Dzierzazna river phenol, chlorophenols,
      guaiacol, trichloroguaiacol, tetrachloroguaiacol, trichlorosyringol and 3,4,5
      trichloroveratole were determined. As no anthropogenic sources are situated
      within the drainage of the Dzierzazna river, we may suppose that most of the
      determined compounds are mainly of natural origin. No or trace concentrations of
      chlorinated methoxyphenols were noted in the water of the Ner river, but a higher
      number, and concentrations of chlorophenols and additionally chlorocatechols were
      determined in this flow. It is also apparent that changes in a number and
      concentrations of phenols in the water of the Ner river did not prove a seasonal
      character, which was typical of the Dzierzazna drainage waters.

PMID- 18048081
TI  - Dental trait expression at the enamel-dentine junction of lower molars in extant
      and fossil hominoids.
AB  - Discrete dental traits are used as proxies for biological relatedness among
      modern human populations and for alpha taxonomy and phylogeny reconstruction
      within the hominin clade. We present a comparison of the expression of lower
      molar dental traits (cusp 6, cusp 7, trigonid crest pattern, and protostylid) at
      the enamel-dentine junction (EDJ) in a variety of extant and fossil hominoid
      taxa, in order to assess the contribution of the EDJ to the morphology of these
      traits at the outer enamel surface (OES). Molars (n=44) were imaged
      nondestructively using high-resolution microCT, and three-dimensional surface
      models of the EDJ and OES were created to compare trait expression at each
      surface. Our results indicate that these dental traits originate at the EDJ, and
      that the EDJ is primarily responsible for their degree of expression at the OES.
      Importantly, variable trait morphology at the EDJ (often not easily recognizable
      at the OES) indicates that different developmental processes can produce traits
      that appear similar at the enamel surface, suggesting caution in intra- and
      intertaxonomic comparisons. The results also highlight the importance of the EDJ
      for understanding the morphological development of discrete traits, and for
      establishing graded scales of variation to compare trait frequency among groups
      for the purpose of taxonomic and/or phylogenetic analysis. Finally, this study
      demonstrates that imaging the EDJ of both worn and unworn fossil hominin teeth
      provides a novel source of information about tooth development and variation in
      crown morphology.

PMID- 18048082
TI  - Assessing ageing of individual T lymphocytes: mission impossible?
AB  - Effector T lymphocytes are the progeny of a limited number of antigen-specific
      precursor cells and it has been estimated that clonotypic human T cells may
      expand million fold on their way reaching high cell numbers that are sufficient
      for immune protection. Moreover, memory T cell responses are characterized by
      repetitive expansion of antigen-specific T cell clonotypes, and limitations in
      the proliferative capacity could lead to immune senescence. Because telomeres
      progressively shorten as a function of cell division, telomere length is a
      powerful indicator of the replicative in vivo history of human T lymphocytes. In
      this review, we summarize observations made over the last decade on telomere
      length dynamics of well-defined T cell populations derived from healthy donors
      and patients with infectious disease or cancer. We focus on T cell
      differentiation, T cell ageing, and natural and vaccine induced immune responses.
      We also discuss the scientific evidence for in vivo replicative senescence of
      antigen-specific T cells, and evaluate the available methods for measuring
      telomere lengths and telomerase activity, and their potential and limitations to
      increase our understanding of T cell physiology.

PMID- 18048083
TI  - An innovative land use regression model incorporating meteorology for exposure
      analysis.
AB  - The advent of spatial analysis and geographic information systems (GIS) has led
      to studies of chronic exposure and health effects based on the rationale that
      intra-urban variations in ambient air pollution concentrations are as great as
      inter-urban differences. Such studies typically rely on local spatial covariates
      (e.g., traffic, land use type) derived from circular areas (buffers) to predict
      concentrations/exposures at receptor sites, as a means of averaging the annual
      net effect of meteorological influences (i.e., wind speed, wind direction and
      insolation). This is the approach taken in the now popular land use regression
      (LUR) method. However spatial studies of chronic exposures and temporal studies
      of acute exposures have not been adequately integrated. This paper presents an
      innovative LUR method implemented in a GIS environment that reflects both
      temporal and spatial variability and considers the role of meteorology. The new
      source area LUR integrates wind speed, wind direction and cloud cover/insolation
      to estimate hourly nitric oxide (NO) and nitrogen dioxide (NO(2)) concentrations
      from land use types (i.e., road network, commercial land use) and these
      concentrations are then used as covariates to regress against NO and NO(2)
      measurements at various receptor sites across the Vancouver region and compared
      directly with estimates from a regular LUR. The results show that, when
      variability in seasonal concentration measurements is present, the source area
      LUR or SA-LUR model is a better option for concentration estimation.

PMID- 18048085
TI  - Blood borne tissue factor revisited.

PMID- 18048084
TI  - Effect of climate on the trophic structure of temperate forested streams. a
      comparison of Mediterranean and Atlantic streams.
AB  - Climate affects many aspects of stream ecosystems, although the presence of
      riparian forests can buffer differences between streams in different climatic
      settings. In an attempt to measure the importance of climate, we compared the
      seasonal patterns of hydrology, input and storage of allochthonous organic
      matter, and the trophic structure (abundance of algae and macroinvertebrates) in
      two temperate forested streams, one Mediterranean, the other Atlantic. Hydrology
      played a leading role in shaping the trophic structure of both streams. Frequency
      and timing of floods and droughts determined benthic detritus storage. Inputs and
      retention of allochthonous organic matter were higher in the Atlantic stream,
      whereas chlorophyll concentration was lower because of stronger light limitation.
      Instead, light availability and scour of particulate organic matter during late
      winter favoured higher chlorophyll concentration in the Mediterranean stream. As
      a result, in the Mediterranean stream grazers were more prevalent and consumers
      showed a higher dependence on autotrophic materials. On the other hand, the
      Atlantic stream depended on allochthonous materials throughout the whole study
      period. The overall trophic structure showed much stronger seasonality in the
      Mediterranean than in the Atlantic stream, this being the most distinctive
      difference between these two types of temperate streams. The different patterns
      observed in the two streams are an indication that climatic differences should be
      incorporated in proper measurements of ecosystem health.

PMID- 18048086
TI  - Differential associations between lipid-lowering drugs, statins and fibrates, and
      venous thromboembolism: role of drug induced homocysteinemia?
AB  - BACKGROUND: Previous studies reported that statin use was associated with a
      decreased risk of venous thromboembolism (VTE), whereas no association was found
      between fibrate use and VTE. This report aims to test the hypothesis that part of
      these contrasting associations is related to total homocysteine level (tHcy).
      MATERIALS AND METHODS: This report from a case-control study included 677 cases
      hospitalised with confirmed VTE and no major acquired risk factor of VTE and
      their 677 controls. Statin and fibrate exposure was defined as a current use of
      drugs at admission. Fasting serum tHcy was measured in all patients. RESULTS: The
      estimated odds ratio for VTE related to statin use was 0.53 (CI 95% 0.37-0.78),
      whereas it was 1.88 (CI 95% 1.29-2.74) for fibrate use. No difference was found
      for tHcy levels between patients who were current users of statin compared to non
      users (17.7 micromol/L+/-7.3 in users vs 18.4 micromol/L+/-8.4 in non users,
      p=0.50). In contrast, fibrate users had a significant higher mean level of tHcy
      than non users (23.2 micromol/L+/-8.7 in users vs 18.4 micromol/L+/-8.4 in non
      users, p<0.0001). Nevertheless, adjustment on tHcy level did not alter
      significance and strength of the association between fibrates and VTE (1.66, CI
      95% 1.07-2.59). CONCLUSIONS: Statin use was associated with a significant
      decreased risk of VTE, whereas fibrate use was associated with a significant
      increased risk of VTE. This last association was independent of tHcy levels.

PMID- 18048087
TI  - Relationship between small-for-gestational age births and maternal thrombophilic
      mutations.
AB  - Small gestational age (SGA) is one of the major causes of fetal mortality and
      morbidity. Altered maternal homeostasis as a result of point mutations in the
      coagulation cascade has been reported as an important risk factor for this
      adverse pregnancy outcome. This study aims to investigate the relationship
      between mother's thrombophilic mutations and SGA deliveries in our population.
      The study group was consisted of sixty-six women who gave birth to one or more
      SGA babies. 104 women who gave birth to appropriate-for-gestational age (AGA)
      babies were sampled for the control group. Restriction fragment size analysis
      were performed by visualizing digested PCR products for Factor V Leiden (G1691A),
      Factor V Cambridge (A1090G), Factor V A1299G, prothrombin G20210A, methylene
      tetrahydropholate reductase C677T, A1298C and T1317C mutations. The results of
      this study indicate that maternal C677T (p=0.01) and A1298C (p<0.01) mutations in
      MTHFR gene may be suggested as risk factors for SGA outcome in our population.
      Therefore, maternal screening of these two mutations in the first trimester of
      pregnancy could help in the assessment of patients.

PMID- 18048088
TI  - Early signaling of inflammation in acute ischemic stroke: clinical and
      rheological implications.
AB  - INTRODUCTION: Several studies have highlighted the role of interleukin-6 (IL-6)
      as an early signal of the inflammatory response following acute ischemic stroke.
      This study examines the potential advantage of employing high-sensitivity (hs)-IL
      6 as a possible biomarker at the early stages of acute stroke for identifying an
      acute phase response and its potential rheological and clinical implications.
      METHODS: Venous blood was obtained from 186 stroke patients within 24 h of
      hospital admission and 3-5 days thereafter in order to characterize an
      inflammatory and hemorheological profile (including erythrocyte aggregation).
      Neurological state was assessed by the National Institutes of Health Stroke Scale
      (NIHSS) and the modified Rankin scale (mRs). RESULTS: While most biomarkers
      displayed elevated concentrations with time, serum concentrations of hs-IL-6
      declined 3-5 days following acute stroke. Initially elevated levels of hs-IL-6 at
      presentation further correlated with unfavorable clinical outcomes (by NIHSS and
      mRs) at both time points. Analysis of variance in the different quartiles
      identified an hs-IL-6 gradient-dependent correlation at both time points, such
      that the higher the initial hs-IL-6 concentration, the higher the elevation in
      inflammatory biomarkers and the poorer the neurological state at both time points
      (p<0.001 for NIHSS and p=0.001 for mRs, for trend across quartiles). CONCLUSIONS:
      This study demonstrates the potential of employing hs-IL-6 as an early stage
      biomarker for the prognosis of acute ischemic stroke. Such an advance would
      provide the means to identify at an early stage the patients who would require
      closer clinical surveillance and/or administration of therapeutic interventions.

PMID- 18048089
TI  - The urokinase-type plasminogen activator/its soluble receptor system is
      independently related to carotid atherosclerosis and associated with CC
      chemokines in uraemic patients.
AB  - INTRODUCTION: The urokinase-type plasminogen activator (uPA)/its soluble receptor
      (suPAR) and CC-chemokines are two systems contributing in the atherosclerosis. We
      try to establish whether these two systems were associated among themselves, and
      the significance of this potential association in relation to carotid
      atherosclerosis in uraemic patients. MATERIALS AND METHODS: We determined uPA,
      suPAR, CC-chemokines: monocyte chemoattractant protein-1 (CCL2), macrophage
      inflammatory proteins (CCL3, CCL4), regulated upon activation, normal T cell
      expressed and secreted (CCL5) and the intima-media thickness (IMT) values in
      uraemic patients on peritoneal dialysis (CAPD), haemodialysis (HD) and healthy
      controls. RESULTS: The values of the uPA/suPAR system, CCL2, CCL4 and IMT in the
      patients significantly exceeded those in controls, whereas CCL5 were lower in the
      patients than in the controls. CCL3 concentrations were similar in all
      investigated groups. CCL2, CCL4 and CCL5 were positively associated with
      uPA/suPAR system. CCL2 and CCL4 were associated with IMT. Multivariate analysis
      showed that uPA, suPAR and age were the strong independent variables linked to
      IMT values. CONCLUSIONS: The carotid atherosclerosis is independently related to
      uPA/its soluble receptor system in dialysis patients. In addition, the strong
      positive associations existed between uPA/suPAR system and CC-chemokines
      suggesting that these two systems could cooperate and influence of
      atherosclerosis in these patients.

PMID- 18048090
TI  - Hemostatic variation during perioperative period of orthotopic liver
      transplantation without venovenous bypass.
AB  - OBJECTIVES: To measure the variations of different parameters in the hemostatic
      system and to analyze their roles in the development of hemostatic disorder in
      patients with orthotopic liver transplantation (OLT) procedures routinely
      performed without venovenous bypass. METHODS: The blood coagulation and
      fibrinolysis parameters were analyzed in 20 patients who underwent liver
      transplantation. Blood samples were drawn from the radial artery at serial time
      points during perioperative period. Prothrombin time (PT), activated partial
      thromboplastin time (aPTT), thrombin time (TT), fibrinogen, vWF, antithrombin III
      (AT-III), protein C (PC), tissue factor pathway inhibitor (TFPI), plasminogen
      (PLG), alpha2-antiplasmin (alpha2-AP), and D-dimer were analyzed. RESULTS:
      Hemoglobin, platelet count, and fibrinogen were significantly decreased during
      anhepatic and reperfusion phases compared with preoperative values (P<0.01). VWF
      activity only showed significant increase during the reperfusion 60 min compared
      with preoperative value (P<0.05). PT, INR, aPTT, and TT were prolonged
      progressively, and they reached the maximum values at the beginning reperfusion
      15 min compared with preoperative values (P<0.01). The AT-III, PC, TFPI, PLG, and
      alpha2-AP levels were decreased significantly and D-dimer level was elevated
      significantly throughout the intraoperative period. In the postoperative period,
      these parameters progressively returned to preoperative levels. CONCLUSIONS: In
      the entire process of OLT operation, coagulation defects, hyperfibrinolysis and
      platelet numbers decrease could develop hemostatic disorder. The data obtained in
      this study might contribute to a better understanding of the pathophysiology and
      assessment of bleeding risk in the OLT.

PMID- 18048091
TI  - Neither ovariectomy nor progestin treatment prevents endometrial neoplasia in
      pten+/- mice.
AB  - OBJECTIVE: Hormonal therapy for type I (endometrioid) endometrial carcinoma is
      employed as both a conservative treatment option and for advanced or recurrent
      disease, but outcome is often poor. Our objective was to test whether
      ovariectomy, or ovariectomy followed by progestin treatment prevents the
      development of endometrial lesions in the pten+/- mouse model of endometrial
      cancer. METHODS: pten+/- mice underwent ovariectomy or sham surgery at 6 or 12
      weeks of age. Groups of mice were sacrificed at 24, 30 or 40 weeks. Different
      cohorts of pten+/- mice were ovariectomized at 6 or 12 weeks of age, followed by
      medroxyprogesterone acetate (MPA) treatment at low or high-dose (25 or 200 mg
      total dose, respectively) over 21 days, beginning at 30 weeks of age. Uteri from
      all mice were examined by routine histology and immunohistochemistry. RESULTS:
      Without MPA treatment, 16 of 18 ovariectomized animals developed endometrial
      neoplasms (atypical hyperplasia or adenocarcinoma), as did all 9 sham surgery
      mice. Immunophenotypes for all tumors were consistent with activation of the
      phosphoinositidyl-3-kinase (PI3K) pathway, showing staining for phosphorylated
      PKB/Akt, phosphorylated S6 ribosomal protein and phosphorylated GSK3alpha/beta.
      All 10 mice treated with either low or high-dose MPA developed endometrial
      tumors, again with persistent activation of the PI3K signaling pathway.
      CONCLUSIONS: Development of endometrial neoplasms and constitutive activation of
      the PI3K pathway in pten+/- mice is not affected by hormonal ablation or by
      progestin treatment. Loss of PTEN expression is common during human endometrial
      cancer development, and this may render lesions resistant to the effects of
      hormonal manipulation leading to treatment failure.

PMID- 18048092
TI  - A synthetic retinoid, TAC-101 (4-[3,5-bis (trimethylsilyl) benzamido] benzoic
      acid), plus cisplatin: potential new therapy for ovarian clear cell
      adenocarcinoma.
AB  - OBJECTIVE: A novel retinoid, TAC-101 (4-[3,5-bis (trimethylsilyl) benzamido]
      benzoic acid), induces apoptosis of ovarian clear cell adenocarcinoma. The
      antitumor effect of TAC-101 alone or combined with cisplatin was tested using
      human ovarian carcinoma. METHODS: Induction of genes related to apoptosis by TAC
      101 or cisplatin was assessed by DNA microarray analysis. TAC-101 (8 mg/kg/day
      orally for 21 days), cisplatin (7 mg/kg intravenously on day 1), or a combination
      of both drugs at the same dosages was administered to nude mice implanted
      subcutaneously with RMG-I or RMG-II clear cell adenocarcinoma cells. The
      antitumor effect was evaluated by calculating the treated/control tumor volume
      ratio at 21 days after implantation. The histoculture drug response assay was
      also performed using fresh surgical specimens of human ovarian cancer to
      determine the 50% inhibitory concentration (IC50). RESULTS: Different apoptosis
      related genes were induced by TAC-101 and cisplatin. Compared with control mice,
      the volume of both RMG-I and RMG-II tumors was significantly reduced (p<0.05) by
      either drug. The IC50 values of cisplatin and TAC-101 showed a significant
      correlation (p<0.01). CONCLUSION: These in vitro findings suggest that a
      combination of TAC-101 and cisplatin may be a potential new treatment for ovarian
      clear cell adenocarcinoma.

PMID- 18048093
TI  - Role of PACAP in the physiology and pathology of the sympathoadrenal system.
AB  - Sympathetic neurons and chromaffin cells derive from common sympathoadrenal
      precursors which arise from the neural crest. Cells from this lineage migrate to
      their final destination and differentiate by acquiring a catecholaminergic
      phenotype in response to different environmental factors. It has been shown that
      the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) and
      its PAC1 receptor are expressed at early stages of sympathetic development, and
      participate to the control of neuroblast proliferation and differentiation. PACAP
      also acts as a neurotransmitter to stimulate catecholamine and neuropeptide
      biosynthesis and release from sympathetic neurons and chromaffin cells, during
      development and in adulthood. In addition, PACAP and its receptors have been
      described in neuroblastoma and pheochromocytoma, and the neuropeptide regulates
      the differentiation and activity of sympathoadrenal-derived tumoral cell lines,
      suggestive of an important role in the pathophysiology of the sympathoadrenal
      lineage. Transcriptome studies uncovered genes and pathways of known and unknown
      roles that underlie the effects of PACAP in the sympathoadrenal system.

PMID- 18048094
TI  - Repeated neonatal separation results in different neurochemical and behavioral
      changes in adult male and female Mongolian gerbils.
AB  - We assessed whether daily separation of Mongolian gerbils (Meriones unguiculatus)
      from mothers and siblings during postnatal days 4-20 would produce behavioral and
      neurochemical changes in adulthood that parallel some features of depression in
      humans. Neonatal separation altered the behavior of adult females in the open
      field test but not in the tail suspension test, and did not affect behavior of
      males. Separated males, but not females, showed a significant decrease in
      hippocampal brain derived neurotrophic factor (BDNF) relative to controls.
      Western blot and optical densitometry measurements in the hippocampus did not
      reveal significant group differences in synaptophysin levels in either sex, but
      there was a tendency toward decreased levels of synaptophysin in the entire
      hippocampus as well as the CA1 hippocampal subregion of separated males. Repeated
      separation of neonates from mothers and siblings led to subtle behavioral and
      neurochemical changes during adulthood that were expressed differently in male
      and female gerbils.

PMID- 18048095
TI  - Structural perturbation of alphaB-crystallin by zinc and temperature related to
      its chaperone-like activity.
AB  - alphaB-crystallin is a small heat shock protein that shows chaperone-like
      activity, as it protects the aggregation of denatured proteins. In this work, the
      possible relationships between structural characteristics and the biological
      activity of alphaB-crystallin were investigated on the native protein and on the
      protein undergoing the separate effects of metal ligation and temperature. The
      chaperone-like activity of alphaB-crystallin increased in the presence of zinc
      and when temperature was increased. By using fluorescent probes to monitor
      hydrophobic surfaces on alphaB-crystallin, it was found that exposed hydrophobic
      patches on the protein surface increased significantly both in the presence of
      zinc and when the temperature was raised from 25 to 37 degrees C. The zinc
      induced increased exposure of lipophilic residues is in agreement with
      theoretical calculations performed on 3D-models of monomeric alphaB-crystallin,
      and may be significant to its increased biological activity.

PMID- 18048097
TI  - Choriogenin mRNA as a sensitive molecular biomarker for estrogenic chemicals in
      developing brackish medaka (Oryzias melastigma).
AB  - Teleost choriogenins, precursors of the inner layer subunits of the egg envelope,
      are regarded as sensitive biomarkers for estrogenic pollutants. In this study,
      two full-length cDNAs, omChgH and omChgL, which encode the choriogenin H and L
      forms, respectively, were isolated from a brackish medaka, Oryzias melastigma.
      17beta-Estradiol (E2; 10 microg/L)-dependent expression of omChgH and omChgL was
      observed starting at embryonic stage 34 and restricted exclusively to the liver.
      In hatchlings, E2 induction of omChgH was stronger than that of omChgL. Static
      exposure of adult fish to E2 (0, 1, 10, 100, and 500 ng/L), 17alpha
      ethinylestradiol (EE2; 0, 1, 10, 100 and 500 ng/L), 4-nonylphenol (NP; 0, 1, 10,
      100, and 200 microg/L), and bisphenol A (BPA; 0, 1, 10, 100, and 200 microg/L) in
      artificial seawater for 7 days resulted in dose-dependent induction of both genes
      in the liver. In the male livers, the sensitivity of omChgH to these estrogenic
      compounds was higher than that of omChgL; the lowest-observed-effect
      concentrations (LOECs) of E2, EE2, NP, and BPA on omChgH were 10 ng/L, 10 ng/L,
      100 microg/L and 100 microg/L, respectively, and on omChgL were 100 ng/L, 100
      ng/L, 100 microg/L, and 200 microg/L, respectively. All these suggest that omChgH
      can be used as a highly sensitive biomarker for monitoring estrogenic chemicals
      in the marine environment.

PMID- 18048098
TI  - Quantifying variability in phase portraits: application to gait ontogeny.
AB  - We describe new Fourier- and shape-based methods for quantifying variation in
      phase-portraits, and re-analyze previously-published ontogenetic and adult data
      [Clark, J. E., & Phillips, S. J. (1993). A longitudinal study of intralimb
      coordination in the first year of independent walking: A dynamical systems
      approach. Child Development, 64, 1143-1157]. Results show considerable variation
      between individuals and through development, but after 6 months of walking some
      gait patterns stabilize.

PMID- 18048096
TI  - Controlled release from multilayer silk biomaterial coatings to modulate vascular
      cell responses.
AB  - A multilayered silk fibroin protein coating system was employed as a drug carrier
      and delivery system to evaluate vascular cell responses to heparin, paclitaxel,
      and clopidogrel. The results demonstrated that the silk coating system was an
      effective system for drug-eluting coatings, such as for stent applications, based
      on its useful micromechanical properties and biological outcomes. Cell attachment
      and viability studies with human aortic endothelial cells (HAECs) and human
      coronary artery smooth muscle cells (HCASMCs) on the drug-incorporated silk
      coatings demonstrated that paclitaxel and clopidogrel inhibited smooth muscle
      cell (SMC) proliferation and retarded endothelial cell proliferation. Heparin
      loaded silk multilayers promoted HAEC proliferation while inhibiting HCASMC
      proliferation, desired outcomes for the prevention of restenosis. The
      preservation of the phenotype of endothelial cells on silk and heparin-loaded
      silk coatings was confirmed with the presence of endothelial markers CD-31, CD
      146, vWF and VE-Cadherin using immunocytochemistry assays. A preliminary in-vivo
      study in a porcine aorta showed integrity of the silk coatings after implantation
      and the reduction of platelet adhesion on the heparin-loaded silk coatings.

PMID- 18048099
TI  - Continuity of father-rated temperament from infancy to middle childhood.
AB  - Continuity of father-rated temperament in Finnish children (n=115) aged from 6
      months (the IBQ) to 5.5 years (the CBQ) was explored within the theoretical
      framework developed by Rothbart. Father-rated activity level, smiling and
      laughter and distress to limitations showed significant differential homotypic
      and heterotypic continuity, while soothability, duration of orienting and fear
      showed significant differential heterotypic continuity. On the level of latent
      superconstructs, father-rated positive and negative infant affectivity accounted
      for 5.1, 22.7 and 10.0% of the variance in childhood extraversion, effortful
      control and negative affectivity, respectively. Inter-parental comparisons (n=109
      family units) revealed that father-rated continuity was similar to mother-rated
      continuity. These findings give empirical credence to Rothbart's theory and to
      father-rated temperamental continuity from infancy onwards.

PMID- 18048100
TI  - Infants in group care: their interactions with professional caregivers and
      parents across the second year of life.
AB  - Seventy children were observed during structured play with their primary
      professional caregivers and three peers in the child care center and with their
      primary caregiving parents at home at 15 and 23 months of age. The same
      structured play tasks were used in the two settings and the quality of the
      children's interactions with caregivers and parents was rated using the same 7
      point scales. As expected, the quality of caregiver-child interactions
      significantly increased between 15 and 23 months. At 15 months, the quality of
      caregiver-child interactions was significantly lower than the quality of parent
      child interactions, particularly with regard to caregiver supportive presence and
      respect for the child's autonomy. At 23 months, however, the quality of caregiver
      child interactions was no longer lower and in some respects even higher than the
      quality of parent-child interactions. At both ages, the children expressed more
      negativity towards their parents than towards their professional caregivers.

PMID- 18048101
TI  - Ameliorating effects of compounds derived from Salvia miltiorrhiza root extract
      on microcirculatory disturbance and target organ injury by ischemia and
      reperfusion.
AB  - Ischemia and reperfusion (I/R) exerts multiple insults in microcirculation,
      frequently accompanied by endothelial cell injury, enhanced adhesion of
      leukocytes, macromolecular efflux, production of oxygen free radicals, and mast
      cell degranulation. Since the microcirculatory disturbance results in injury of
      organ involved, protection of organ after I/R is of great importance in clinic.
      Salvia miltiorrhiza root has long been used in Asian countries for clinical
      treatment of various microcirculatory disturbance-related diseases. This herbal
      drug contains many active water-soluble compounds, including protocatechuic
      aldehyde (PAl), 3,4-dihydroxyphenyl lactic acid (DLA) and salvianolic acid B
      (SalB). These compounds, as well as water-soluble fraction of S. miltiorrhiza
      root extract (SMRE), have an ability to scavenge peroxides and are able to
      inhibit the expression of adhesion molecules in vascular endothelium and
      leukocytes. Moreover, lipophilic compounds of SMRE also prevent the development
      of vascular damage; NADPH oxidase and platelet aggregation are inhibited by
      tanshinone IIA and tanshinone IIB, respectively, and the mast cell degranulation
      is blunted by cryptotanshinone and 15,16-dihydrotanshinone I. Thus, the water
      soluble and lipophilic compounds of SMRE appear to improve the I/R-induced
      vascular damage multifactorially and synergically. This review will summarize the
      ameliorating effect of compounds derived from SMRE on microcirculatory
      disturbance and target organ injury after I/R and will provide a new perspective
      on remedy with multiple drugs.

PMID- 18048102
TI  - [Editorial].

PMID- 18048103
TI  - [Consciousness and emotion].
AB  - This article focuses on the processes that lead to awareness of our own emotions,
      which deserve particular attention in contemporary models of emotional
      consciousness. The subjective component of emotion, or emotional experience, was
      for a long time the most neglected aspect in the study of emotions although it
      already constituted the initial point of discussion in the famous William James
      still asked question : What is an emotion? More than a century later,
      contemporary theories debate about this heritage. We examine the successive
      historic contributions to the question of the determinants of our own emotional
      experience: from James-Lange bodily changes to cognitive appraisal theories, also
      relating the major role that the fundamental emotions theory attributed to facial
      expressions. Twenty years after the debate about primacy of cognition or emotion,
      both physiological-somatic and cognitive components are integrated in
      contemporary approaches to emotions. However, their respective degree of
      implication varies according to the different levels of emotional consciousness
      which are modelized. It is on the last level that present models focus, level
      that leads to consciousness of our emotional experience, benefiting from the
      contributions of cognitive neurosciences. Models differ according to the role
      devoted to neuronal substrates in determining emotional experience, but they
      converge on the specification of a last level of consciousness, which is the only
      one that allows the subject to be conscious of emotion as it is experienced
      (feeling) and that what he is experiencing is an emotion. Then, different models
      of emotional consciousness account for different varieties of emotion experience
      and also for various cases of << unconscious >> emotions, that is occurrence of
      emotion with a lack of awareness.

PMID- 18048104
TI  - [A scientific model of consciousness: implications for neuropsychiatic diseases].
AB  - Consciousness is an essential property of human cognition. According to the
      "Global neuronal workspace" hypothesis designed by Dehaene et al., consciousness
      results from amplification and synchronisation of distant processors.
      Frontoparietal loops play a crucial role in this large scale synchronisation. At
      any given time, many modular cerebral networks are active in parallel and process
      information unconsciously. An information becomes conscious, however, if the
      neural population that represents it is mobilized by top-down attentional
      amplification into a brain-scale state of coherent activity. This long-distance
      connectivity makes the information available to a variety of processes including
      perceptual categorization, long-term memorization, evaluation, and intentional
      action. Behavioral as well as neuroimaging studies using masked subliminal
      perception support this theoretical view. Among neuropsychiatric disorders, many
      neuroscientific studies have been devoted to schizophrenia. Some of them conclude
      on a global brain disconnectivity rather than on specific and localised
      perturbations. Hence conscious integration may be the core deficit in cognitive
      disabilities observed in schizophrenia. As shown in recent results, threshold for
      access to consciousness in schizophrenic patients compared with controls is
      elevated whereas unconscious processes, such as the ones involved in subliminal
      priming remain effective. We conclude on the potential use of the "global
      neuronal workspace" model in other neuropsychiatric diseases such as Alzheimer's
      disease or multiple sclerosis.

PMID- 18048105
TI  - [Cerebral imaging and physiopathology of Alzheimer's disease].
AB  - Alzheimer's disease (AD) is characterised by macroscopic cerebral damages which
      can be studied in vivo with neuroimaging techniques, even at the earliest stage.
      Studies were conducted in patients with amnestic Mild Cognitive Impairment (MCI)
      who best represent incipient AD. Right temporo-parietal hypometabolism, assessed
      by resting-state (18)FDG-PET, distinguishes patients who further develop AD from
      those who remain stable. From the pre-dementia stage of MCI, atrophy of the
      hippocampal region detected with structural MRI contrasts with functional
      alteration of the posterior cingulate gyrus measured with (18)FDG-PET and SPECT.
      Results from resting-state fMRI confirm this pattern of functional abnormalities
      and highlight changes in the hippocampal region functional connectivity,
      decreased with the posterior cingulate region, and increased with some frontal
      areas. Altogether with a structural connectivity impairment highlighted by DTI,
      those results support the hypothesis of a dysconnexion between the hippocampal
      and the posterior cingulate regions. Finally, activation fMRI data support the
      hypothesis of a functional compensation involving not only the frontal cortex but
      also, at the pre-dementia stage, the hippocampal region. Thus, this synthesis
      focuses on the hypotheses of dysconnexion and functional compensation, suggested
      to explain the discrepancies between the structural and functional alteration
      patterns, as well as on relevant results from resting-state fMRI, DTI and
      activation fMRI studies. Furthermore, this synthesis emphasizes the relevance of
      neuroimaging for the early detection of AD.

PMID- 18048106
TI  - [Deficits in inhibitory processes in normal aging and patients with Alzheimer's
      disease: a review].
AB  - Empirical data suggest that inhibitory processing is impaired in normal aging. A
      decrease in inhibitory processing may also play an important role in the
      cognitive changes occurring in the early stages of Alzheimer's disease. The
      comparison of inhibitory deficits in Alzheimer's disease and normal aging
      emphasizes the need to discriminate quantitative changes in inhibitory
      functioning from qualitative changes which may be specifically related to the
      disease process. Inhibitory deficits in normal old adults and patients with
      Alzheimer's disease, suggest different levels of implication of the inhibitory
      processes. In the cognitive literature, the construct of inhibition, frequently
      used, is however difficult to define as it refers to many different phenomena.
      The question of whether or not inhibitory processes are to be considered as a
      single unit is challenging, and many authors suppose the existence of several
      distinct inhibitory mechanisms. A taxonomy of inhibition, based on proposals from
      Nigg and Soltzfus et al., is proposed to facilitate studies of inhibitory
      dysfunction. Such approach allows a clarification between inhibition deficits
      specific to normal aging and to Alzheimer's disease.

PMID- 18048107
TI  - [Conversion disorder in the elderly].
AB  - The dismemberment of the concept of neurosis, particularly of hysteria, in the
      current classifications (DSM-III and following, ICD-10) has led the authors to
      consider the concept of somatisation and the various situations included in it.
      Somatic disorders as the manifestation of a mental disorder, often of a
      depressive or anxious nature, bring back to the forefront both hysteria and its
      semiological forms under the global term "somatoform disorders", and in parallel
      with new pathologies, somatic symptoms as specific behaviors associated with the
      representation of a morbid condition from the point of view of an inhabitual
      physical perception. The expression of the psychic apparatus into the body, and
      its various clinical manifestations, has no direct specificity in the elderly.
      However, it is both frequent, and frequently misunderstood, thus requiring
      particular vigilance from the physician when confronted with physical complaints
      among elderly patients in whom the link between the body and the psychic
      apparatus takes on a particular role with the approach of death and the
      bereavement process that it requires. A structural approach, and search for event
      driven factors and psychodynamic elements should be the key points of the
      clinician's approach.

PMID- 18048108
TI  - [Elderly distress: cognitive schemas identification].
AB  - International classifications of psychiatric disorders appear to be insufficient
      to account for the psychological distress associated with aging. Identification
      of cognitive schemas can be very useful for the diagnostic and therapeutic levels
      in aged subjects. The aim of this study was to explore the facets of cognitive
      distress in these subjects, that is how can be integrated specific diagrams
      related to psychological changes related to aging with more general schemas
      identified with young adults, and whose interest was confirmed in old subjects.
      An inventory of sixty thoughts representative of maladaptive schemas was proposed
      to 160 subjects aged from 65 to 102 years and to a control group of 38 subjects
      aged from 50 to 64 years. The factorial analysis results showed that 9 distinct
      schemas accounted for 60% of the explained variance: six general (fear of losing
      control, dependence, vulnerability, abandonment, incompetence, self-sacrifice)
      and three specific to aging (disengagement, refusal of assistance, loss of
      individuality). A minority of schemas presented marked links with depression or
      anxiety without never merging with their assessment. In the same way, autonomy
      and institutionalization were significantly linked to some schemas, in particular
      those specific to aging. The interest to develop an standardized inventory from
      this set of schemas is discussed.

PMID- 18048110
TI  - [The beginnings of robotic surgery--from the roots up to the da Vinci
      telemanipulator system].
AB  - The history of the robotic surgery is only 22 years old. The article gives a
      short overview regarding the history of robotics, the surgical robots, the da
      Vinci telemanipulator system and some further commercial and experimental
      surgical robotic surgical simulation is also emphasized. Robotic surgery has its
      own place within the following concepts: 1. computer assisted surgery (CAS), 2.
      computer integrated surgery (CIS), 3. surgical automation, 4. surgical system
      integration and 5. artificial intelligence (AI). At the end of the paper there
      are some important sources of informations regarding robotic surgery.

PMID- 18048109
TI  - [Executive functioning and normal aging: a study of arithmetic word-problem
      solving].
AB  - Recent studies suggest that executive functions are among the first cognitive
      functions to decline with normal aging. METHODS: We studied the effect of age on
      executive functions using a set of 13 arithmetic word problems including 9
      problems of increasing complexity which were solvable in 2, 3, 4 operations, and
      4 aberrant problems. Three groups participated in the study: 18 young, 18 adult
      and 18 elderly participants. RESULTS: The results showed that elderly
      participants were more impaired to resolve complex arithmetic word problems,
      without deficit in their ability to eliminate aberrant problems. CONCLUSION: The
      current elderly sample has a dissociated pattern of performance similar to that
      of some patients with frontal lobe lesions. In these patients, relations were
      found between the inability to generate correct algorithms of resolution for
      arithmetic word problems of increasing complexity and lesions in the dorsolateral
      prefrontal cortex, and between the impaired inhibition of unsolvable word
      problems and lesions in the orbitofrontal regions. We suggest that cognitive
      aging could be better interpreted in terms of changes in some frontal systems
      rather than in all-encompassing frontal deterioration.

PMID- 18048111
TI  - [The maternal and fetal outcome of 122 triplet pregnancies].
AB  - INTRODUCTION: The wide use of infertility drugs and assisted reproduction has
      resulted in 4- to 5-fold increase in the incidence of triplet pregnancies, which
      carry an extremely high risk of maternal complications and adverse perinatal
      outcome. In Hungary, reduction of multifetal pregnancies is available for all
      pregnant women with multifetal gestation since 1998. The goal of the procedure is
      to ensure better outcome for surviving fetuses. Counseling of pregnant patients
      should include the maternal and fetal risks of triplet gestation without
      multifetal pregnancy reduction. AIM: To assess the risk of maternal
      complications, stillbirth, perinatal and neonatal mortality rates, and risk of
      neonatal morbidity in non-reduced triplets in a large case series, representing
      the Hungarian triplet population. METHODS: The study population consisted of
      triplets delivered between July 1st, 1990 and June 30th, 2006, at the 1st
      Department of Obstetrics and Gynecology. All three fetuses had to be alive on the
      18th-week ultrasound scan to be eligible. RESULTS: Out of the 122 cases, 8 (6.6%)
      ended in midtrimester miscarriage, 114 (93.4%) ended in delivery. There were no
      maternal deaths. The most common antepartum maternal complications were pregnancy
      induced hypertension (16.7%), gestational diabetes mellitus (18.4%),
      thrombocytopenia (20.2%), anemia (16.7%) and intrahepatic cholestasis (9.7%).
      Preterm labor requiring tocolysis occurred in 57.9%, preterm premature rupture of
      membranes in 32.5%. Prophylactic cerclage was performed in 15.8% of cases, and
      69.3% of patients received steroid prophylaxis. The mean gestational age at
      delivery was 32.3 +/- 3.2 weeks. The rates of very early (<28 weeks) and early
      (<32 weeks) preterm deliveries were 8.8% and 42.1%, respectively. The mean 5
      minute Apgar score was 9.2 +/- 0.8, and the mean birth weight at delivery was
      1664 +/- 506 g. 38.0% of infants were very low birth weight (<1500 g).
      Stillbirth, crude perinatal mortality and corrected perinatal mortality rates
      were 23.4 per thousand, 64.3 per thousand and 27.4 per thousand, respectively.
      11.7 per thousand of infants had some major congenital anomaly. 54.4% of infants
      required ventilation or oxygen therapy or both. The most common neonatal
      complication were respiratory distress (17.1%), transitory tachypnea (5.2%),
      sepsis or pneumonia (25.5%), intraventricular hemorrhage (4.3%) and jaundice
      (11.4%). CONCLUSIONS: Both the maternal and neonatal risks should be considered
      when patients with triplets are counseled before the decision to continue the
      triplet gestation or to choose multifetal pregnancy reduction is made.

PMID- 18048112
TI  - [Clinical utilization of combined rosiglitazone and glimepiride in the treatment
      of type 2 diabetes mellitus].
AB  - The cardiovascular mortality rate increases worldwide. The most important factor
      of the lethal outcome is the type 2 diabetes mellitus. For the treatment of this
      disease there are several preparations, thus the drugs increasing insulin
      secretion (insulin secretagogues), the compounds enhancing insulin effect
      (insulin sensitisers) and glucose absorption inhibitors. These can be applied
      both in monotherapy and in combination mode. Among the drugs approved the
      combination of glimepiride and rosiglitazone have got a great importance in
      routine use. Glimepiride stimulates the beta-cell secretion and leads to
      reduction of blood glucose values, rosiglitazone stimulates peroxisome
      proliferator-activated receptor-gamma and improves insulin resistance, at the
      vascular and metabolically active cells. The combination of glimepiride and
      rosiglitazone is generally well tolerated and their use of a fixed combination
      may lead to improved adherence of the patients to their therapy.

PMID- 18048113
TI  - [Evaluation of second-line chemotherapies most often used in recurrent epithelial
      ovarian cancer].
AB  - INTRODUCTION: Second-line chemotherapies result in a progression-free interval of
      2,3-42 months. AIM: The authors evaluated the efficacy of second-line paclitaxel
      carboplatin, topotecan, and cisplatin-epirubicin-etoposide combinations. METHODS:
      Paclitaxel-carboplatin (175 mg/m2 and AUC 5) in 3-week intervals and topotecan
      (1.5 mg/m2/d1-3) in 3-week intervals was given to 13 and 16 patients. The triple
      combination of cisplatin-epirubicin-etoposide was applied in 48 patients in 4
      week courses, with doses of 33 mg/m2/d1-3, 60 mg/m2/d1, and 100 mg/m2/d1-3.,
      respectively. The progression-free interval was calculated by the product limit
      method of Kaplan-Meier. RESULTS: A significantly better progression-free interval
      was observed in treatments with paclitaxel-carboplatin and cisplatin-epirubicin
      etoposide compared to the topotecan chemotherapy (5 and 5.5 months vs. 4 months,
      respectively, p = 0.0324 and p = 0.0087). A better progression-free interval was
      found in the platinum-sensitive tumors compared to the platinum-resistant ones by
      the above mentioned combinations (6 and 3.5 months, 7 and 4 months, and 6.5 and
      3.5 months, respectively). CONCLUSION: The lower priced cisplatin-epirubicin
      etoposide combination resulted in a slightly better efficacy compared to the 2
      other treatments both in platinum-sensitive and platinum-resistant tumors.

PMID- 18048114
TI  - [Effective treatment of a hormonally inactive carcinoid tumour with somatostatin
      analogues: application of serum chromogranin-A for clinical follow-up].
AB  - INTRODUCTION: Hormonally inactive carcinoids represent a significant proportion
      of all carcinoids tumours. Classical biochemical and hormonal parameters are not
      suitable for the diagnosis and follow-up of these tumours. However, the tumour
      marker chromogranin A that is characteristic for several neuroendocrine tumours
      and secreted by the majority of these tumours as well, may offer a better means
      of diagnosis and follow-up. Somatostatin receptors are expressed by hormonally
      inactive carcinoids and the presence of these receptors has important diagnostic
      and therapeutic consequences. CASE REPORT: The authors present the history of a
      patient with a hormonally inactive bronchial carcinoid tumour. After surgical
      removal of the bronchial carcinoid, liver metastases developed which were found
      to be somatostatin receptor positive. Somatostatin analogue treatment was
      introduced, followed by Yttrium-isotope labelled somatostatin analogue therapy.
      Serum chromogranin A was elevated before somatostatin treatment, and gradually
      decreased in parallel with therapy. The size of liver metastases remained
      unchanged during treatment. CONCLUSIONS: Chromogranin A can be efficiently
      applied for the clinical follow-up of hormonally inactive carcinoid tumours.
      Somatostatin analogues may be effective for preventing tumour progression not
      only in hormone-secreting but also in hormonally inactive carcinoid tumours.

PMID- 18048117
TI  - [Interview with Dr. Sandor Eckhardt].

PMID- 18048118
TI  - An optimal DNA segmentation based on the MDL principle.
AB  - The biological world is highly stochastic and inhomogeneous in its behaviour.
      There are regions in DNA with a high concentration of G or C bases; stretches of
      sequences with an abundance of CG dinucleotide (CpG islands); coding regions with
      strong periodicity-of-three pattern, and so forth. Transitions between these
      regions of DNA, known also as change points, carry important biological
      information. Computational methods used to identify these homogeneous regions are
      called segmentations. Viewing a DNA sequence as a non-stationary process, we
      apply recent novel techniques of universal source coding to discover stationary
      (possibly recurrent) segments. In particular, the Stein-Ziv lemma is adopted to
      find an asymptotically optimal discriminant function that determines whether two
      DNA segments are generated by the same source assuring exponentially small false
      positives. Next, we use the Minimum Description Length (MDL) principle to select
      parameters that lead to a linear-time segmentation algorithm. We apply our
      algorithm to human chromosome 9 and chromosome 20 to discover coding and
      noncoding regions, starting positions of genes, as well as the beginning of CpG
      islands.

PMID- 18048119
TI  - Dynamic visual data mining: biological sequence analysis and annotation using
      SeqVISTA.
AB  - In the post-genomic era, the volume of public sequence databases is increasing
      exponentially and visualisation-centric techniques have become more and more
      important in biological sequence analysis and annotation. In this paper, we
      present a methodology called dynamic visual data mining (DVDM), which combines
      biological object modelling, interactive display, and data analysis tools into
      one integrative platform. Using Java Development Kit v1.4, an object-oriented
      software named SeqVISTA has been developed based on DVDM. To illustrate the
      application of SeqVISTA, the following examples are shown: regular expression
      pattern matching; comparative analysis of alternative exon splicing patterns;
      Fourier analyses; exon prediction (MZEF and GENSCAN). Overall, we argue that DVDM
      is an important technique for biologists to unveil the information hidden behind
      the large genomic and proteomic databases, and SeqVISTA provides a versatile tool
      that integrates multiple computational algorithms for meeting biologists' data
      mining needs.

PMID- 18048120
TI  - How noisy and replicable are DNA microarry data?
AB  - This paper analyses variability in highly replicated measurements of DNA
      microarray data conducted on nylon filters and Affymetrix GeneChips with
      different cDNA targets, filters, and imaging technology. Replicability is
      assessed quantitatively using correlation analysis as a global measure and
      differential expression analysis and ANOVA at the level of individual genes.

PMID- 18048121
TI  - A three-stage framework for gene expression data analysis by L1-norm support
      vector regression.
AB  - The identification of discriminative genes for categorical phenotypes in
      microarray gene expression data analysis has been extensively studied, especially
      for disease diagnosis. In recent biological experiments, continuous phenotypes
      have also been dealt with. For example, the extent of programmed cell death
      (apoptosis) can be measured by the level of caspase 3 enzyme. Thus, an effective
      gene selection method for continuous phenotypes is desirable. In this paper, we
      describe a three-stage framework for gene expression data analysis based on L1
      norm support vector regression (L1-SVR). The first stage ranks genes by recursive
      multiple feature elimination based on L1-SVR. In the second stage, the minimal
      genes are determined by a kernel regression, which yields the lowest ten-fold
      cross-validation error. In the last stage, the final non-linear regression model
      is built with the minimal genes and optimal parameters found by leave-one-out
      cross-validation. The experimental results show a significant improvement over
      the current state-of-the-art approach, i.e., the two-stage process, which
      consists of the gene selection based on L1-SVR and the third stage of the
      proposed method.

PMID- 18048122
TI  - BioStar models of clinical and genomic data for biomedical data warehouse design.
AB  - Biomedical research is now generating large amounts of data, ranging from
      clinical test results to microarray gene expression profiles. The scale and
      complexity of these datasets give rise to substantial challenges in data
      management and analysis. It is highly desirable that data warehousing and online
      analytical processing technologies can be applied to biomedical data integration
      and mining. The major difficulty probably lies in the task of capturing and
      modelling diverse biological objects and their complex relationships. This paper
      describes multidimensional data modelling for biomedical data warehouse design.
      Since the conventional models such as star schema appear to be insufficient for
      modelling clinical and genomic data, we develop a new model called BioStar
      schema. The new model can capture the rich semantics of biomedical data and
      provide greater extensibility for the fast evolution of biological research
      methodologies.

PMID- 18048123
TI  - Mining and analysing scale-free protein-protein interaction network.
AB  - Protein-protein interaction network is essential to understand the fundamental
      processes that govern cell biology. In this paper, we integrate information
      extraction and data mining techniques to extract and mine the scale-free protein
      protein interaction network from biomedical literature. The experiments on around
      1,600 chromatin proteins indicate that our system is very promising for mining
      and analysing protein-protein interaction network.

PMID- 18048124
TI  - Signal processing for functional analysis of protein mutants.
AB  - We present a new technique to predict the functional behaviour of protein mutants
      using their primary sequence. The amino acid sequences of proteins are used to
      form biochemical signals. Signal processing techniques are used to extract
      functionally meaningful measures from these signals. These computational measures
      are then used to distinguish functional classes of mutant proteins.

PMID- 18048125
TI  - An overview of protein-folding techniques: issues and perspectives.
AB  - The importance of protein folding has been recognised for many years. Almost a
      half century ago, Linus Pauling discovered two quite simple, regular arrangements
      of amino acids--the alpha-helix and the beta-sheet that are found in almost every
      protein. In the early 1960s, Christian Anfinsen showed that the proteins actually
      "tie" themselves: If proteins become unfolded, they fold back into proper shape
      of their own accord; no shaper or folder is needed. The nature of the unfolded
      state plays a great role in understanding proteins. Alzheimer's disease, cystic
      fibrosis, mad cow disease, and many cancers are inherited emphysema. Recent
      discoveries show that all these apparently unrelated diseases result from protein
      folding gone wrong. Theoretical and computational studies have recently achieved
      noticeable success in reproducing various features of the folding mechanism of
      several small to medium-sized fast-folding proteins. This survey presents the
      state-of-the-art in protein structure prediction methods from a computer
      scientist perspective.

PMID- 18048126
TI  - Highly scalable algorithms for robust string barcoding.
AB  - String barcoding is a recently introduced technique for genomic based
      identification of microorganisms. In this paper, we describe the engineering of
      highly scalable algorithms for robust string barcoding. Our methods enable
      distinguisher selection based on whole genomic sequences of hundreds of
      microorganisms of up to bacterial size, on a well equipped workstation.
      Experimental results on both randomly generated and NCBI genomic data show that
      whole-genome based selection results in a number of distinguishers nearly
      matching the information theoretic lower bounds for the problem.

PMID- 18048127
TI  - Identifying d positive clones in the presence of inhibitors.
AB  - Farach et al. introduced the inhibitor model in pooling design, where existence
      of a single inhibitor clone in a pool dictates its outcome to be negative
      regardless of the existence of positive clones in the pool. Various sequential or
      multiround pooling designs have been given to identify all the positive clones
      under the inhibitor model. Recently, Hwang and Liu gave a (one round) pooling
      design for the inhibitor model which is error tolerant. More specifically,
      suppose the set of n clones to be screened contains up to d positive clones, up
      to r inhibitors and the pooling experiments can generate up to e errors, they
      show that a (d + r + 2e)-disjunct matrix does the job. In this paper, we give a
      pooling design for the case that among n clones exactly d are positive. We reduce
      the requirement of (d + r + 2e)-disjunctness to (d + r + e)-disjunctness, which
      would mean the saving of many pools. We also show how our design can be used to
      identify all positive clones when their number is, at most, d.

PMID- 18048128
TI  - Logistic support vector machines and their application to gene expression data.
AB  - One important feature of the gene expression data is that the number of genes m
      far exceeds the number of samples n. When applied to analyse the gene expression
      data, standard statistical methods do not work well when n < m. Development of
      new methodologies or modification of existing methodologies is needed for the
      analysis of microarray data. Support vector machine (SVM) has been applied in
      gene expression data classification. In traditional SVM classification, a
      classifier is usually built by a small subset of samples called support vectors.
      This may cause a loss of available information since the number of samples in a
      gene expression dataset is usually very small. In this paper, we introduce a
      logistic support vector machine (LSVM) algorithm for the classification task. In
      LSVM, all the samples are used as support vectors and parameters are estimated
      via the maximum a posteriori (MAP) estimation procedure. The proposed algorithm
      also has the advantage of providing an estimate of the underlying probability.
      This algorithm was applied to five different gene expression datasets.
      Computational results show that compared with popular classification methods such
      as traditional SVM, our algorithm usually leads to an improvement in
      classification accuracy.

PMID- 18048129
TI  - Effective statistical features for coding and non-coding DNA sequence
      classification for yeast, C. elegans and human.
AB  - This study performs a quantitative evaluation of the different coding features in
      terms of their information content for the classification of coding and non
      coding regions for three species. Our study indicated that coding features that
      are effective for yeast or C. elegans are generally not very effective for human,
      which has a short average exon length. By performing a correlation analysis, we
      identified a subset of human coding features with high discriminative power, but
      complementary in their information content. For this subset, a classification
      accuracy of up to 90% was obtained using a simple kNN classifier.

PMID- 18048130
TI  - Recombination and phylogeny: effects and detection.
AB  - The role of phylogeny in guiding comparative studies is rapidly growing in the
      post genomic era. Most phylogeny reconstruction methods though, assume a single
      tree underlying a given alignment of sequences. However, when events such as
      recombination occur, different regions in the alignment may have different
      underlying trees. In this paper, we demonstrate via simulations, the effect of
      recombination on the accuracy of phylogeny reconstruction methods. Our results,
      coupled with the significance of recombination as an evolutionary mechanism, make
      it imperative to devise efficient and accurate methods for detecting
      recombination in sequence datasets. Hence, we introduce a simple, yet effective,
      method for detecting recombination in a given alignment, based on incongruence
      among phylogenetic trees in different regions of the alignment. We have studied
      the performance of our method on synthetic and biological datasets, and obtained
      good results.

PMID- 18048131
TI  - A districted neural network for start codon prediction.
AB  - Following the theory on regional and national voting, we constructed a regional
      voting version NN from Pedersen-Nielsen's NN for start codon prediction in
      nucleotide sequences. Experiments on the TIS data of vertebrate and Arabidopsis
      thaliana sequences showed improved performances (Matthews correlation
      coefficients) of 7% and 14% over the original NN.

PMID- 18048132
TI  - Family trio phasing and missing data recovery.
AB  - Although there exist many phasing methods for unrelated adults or pedigrees,
      phasing and missing data recovery for data representing family trios is lagging
      behind. This paper is an attempt to fill this gap by considering the following
      problem. Given a set of genotypes partitioned into family trios, find for each
      trio a quartet of parent/offspring haplotypes explaining each trio without
      recombinations and recovering the SNP values missed in given genotype data. Our
      contributions include: formulating the pure-parsimony trio phasing without
      recombinations and the trio missing data recovery problems; proposing new greedy
      and integer linear programming based solution methods; extensive experimental
      validation of proposed methods showing advantage over the previously known
      methods.

PMID- 18048133
TI  - Simultaneous alignment and structure prediction of three RNA sequences.
AB  - Comparative RNA sequence analyses have contributed remarkably accurate
      predictions. The recent determination of the 30S and 50S ribosomal subunits
      bringing more supporting evidence. Several inference tools are combining free
      energy minimisation and comparative analysis to improve the quality of secondary
      structure predictions. This paper investigates the following hypotheses: the use
      of three input sequences improves the average accuracy compared to predictions
      based on two input sequences; the worse prediction (minimum accuracy) for any
      sequence should be more accurate when three input sequences are used rather than
      two; finally, the consensus structure of three sequences is probably less
      representative of the individual sequences. The average coverage should be less.

PMID- 18048134
TI  - Linear reduction method for predictive and informative tag SNP selection.
AB  - Constructing a complete human haplotype map is helpful when associating complex
      diseases with their related SNPs. Unfortunately, the number of SNPs is very large
      and it is costly to sequence many individuals. Therefore, it is desirable to
      reduce the number of SNPs that should be sequenced to a small number of
      informative representatives called tag SNPs. In this paper, we propose a new
      linear algebra-based method for selecting and using tag SNPs. We measure the
      quality of our tag SNP selection algorithm by comparing actual SNPs with SNPs
      predicted from selected linearly independent tag SNPs. Our experiments show that
      for sufficiently long haplotypes, knowing only 0.4% of all SNPs the proposed
      linear reduction method predicts an unknown haplotype with the error rate below
      2% based on 10% of the population.

PMID- 18048135
TI  - Ridge regression based hybrid genetic algorithms for multi-locus quantitative
      trait mapping.
AB  - Genetic algorithms (GAs) are increasingly used in large and complex optimisation
      problems. Here we use GAs to optimise fitness functions related to ridge
      regression, which is a classical statistical procedure for dealing with a large
      number of features in a multivariable, linear regression setting. The algorithm
      avoids overfitting, gracefully handles collinearity and leads to easily
      interpretable results. We use the method to model the relationship between a
      quantitative trait and genetic markers in a mouse cross involving 69 F2 mice. The
      approach will be useful in the context of many genomic data sets where the number
      of features far exceeds the number of observations and where features can be
      highly correlated.

PMID- 18048136
TI  - A software system for gene sequence database construction based on fast
      approximate string matching.
AB  - We propose a web-based software system for sequence acquisition and database
      construction. An example application of this system is to construct a ribosomal
      RNA gene (rDNA) sequence database to facilitate the study of microbial
      communities. A fast and accurate approximate string matching algorithm is
      implemented to fetch rDNA sequences sandwiched by two given primers from GenBank.
      A homology search algorithm based on Basic-Local-Alignment-Search-Tool (BLAST) is
      then used to extract rDNA sequences that do not contain the primers. This two
      step process leads to an rDNA sequence database for a specific taxonomic group.
      We consider the distance between the occurrences of the two given primers,
      mismatches and degeneracy when performing string matching. In the homology
      search, a chaining algorithm is combined with BLAST to obtain global alignments
      based on local alignments. This system can be used in many biological
      applications.

PMID- 18048137
TI  - A bottom-up clustering algorithm to detect ncRNA molecules with a common
      secondary structure.
AB  - Recently, there has been much interest in exploring the universe of non-protein
      coding RNA molecules that operate in the cell. We suggested an approach using a
      simple two-dimensional representation of RNA molecules that can identify common
      structural features of RNA molecules. Here, we address a common situation in
      which there is a large and diverse population of candidate molecules, and the
      task is to identify a small subset (or subsets) of RNA molecules that share a
      common structure. With certain constraints, our algorithm enumerates all possible
      sets of RNA molecules that have a common structure by first grouping together all
      molecules that have a single common structural feature and, using an iterative
      approach, search for subsets that share additional structural motifs. In a
      computational experiment, we were able to detect members of three small classes
      of RNA molecules, each containing several dozen members that were mixed in a
      population of 2778 non-coding sequences common to two trypanosome species.

PMID- 18048138
TI  - Corpus based learning of stochastic, context-free grammars combined with Hidden
      Markov Models for tRNA modelling.
AB  - In this paper, a new method for modelling tRNA secondary structures is presented.
      This method is based on the combination of stochastic context-free grammars
      (SCFG) and Hidden Markov Models (HMM). HMM are used to capture the local
      relations in the loops of the molecule (nonstructured regions) and SCFG are used
      to capture the long term relations between nucleotides of the arms (structured
      regions). Given annotated public databases, the HMM and SCFG models are learned
      by means of automatic inductive learning methods. Two SCFG learning methods have
      been explored. Both of them take advantage of the structural information
      associated with the training sequences: one of them is based on a stochastic
      version of the Sakakibara algorithm and the other one is based on a Corpus based
      algorithm. A final model is then obtained by merging of the HMM of the
      nonstructured regions and the SCFG of the structured regions. Finally, the
      performed experiments on the tRNA sequence corpus and the non-tRNA sequence
      corpus give significant results. Comparative experiments with another published
      method are also presented.

PMID- 18048139
TI  - Improved protein fold assignment using support vector machines.
AB  - Because of the relatively large gap of knowledge between number of protein
      sequences and protein structures, the ability to construct a computational model
      predicting structure from sequence information has become an important area of
      research. The knowledge of a protein's structure is crucial in understanding its
      biological role. In this work, we present a support vector machine based method
      for recognising a protein's fold from sequence information alone, where this
      sequence has less similarity with sequences of known structures. We have focused
      on improving multi-class classification, parameter tuning, descriptor design, and
      feature selection. The current implementation demonstrates better prediction
      accuracy than previous similar approaches, and has similar performance when
      compared with straightforward threading.

PMID- 18048140
TI  - Cellular function prediction and biological pathway discovery in Arabidopsis
      thaliana using microarray data.
AB  - Determination of protein function and biological pathway is one of the most
      challenging problems in the post-genomic era. To address this challenge, we have
      developed a new integrated probabilistic method for cellular function prediction
      using microarray gene expression profiles, in conjunction with predicted protein
      protein interactions and annotations of known proteins. Our approach is based on
      a novel assessment for the relationship between correlation of two genes'
      expression profiles and their functional relationship in terms of the Gene
      Ontology (GO) hierarchy. We applied the method for function prediction of
      hypothetical genes in Arabidopsis. We have also extended our method using
      Dijkstra's algorithm to identify the components and topology of signaling pathway
      of phosphatidic acid as a second messenger in Arabidopsis.

PMID- 18048141
TI  - Fast chromosome karyotyping by auction algorithm.
AB  - We consider the problem of automated classification of human chromosomes or
      karyotyping and study discrete optimisation algorithms to solve the problem as
      one of joint maximum likelihood classification. We demonstrate that the auction
      algorithm offers a simpler and more efficient solution for chromosome karyotyping
      than the previously known transportation algorithm, while still guaranteeing
      global optimality. This improvement in algorithm efficiency is made possible by
      first casting chromosome karyotyping into a problem of optimal assignment and
      then exploiting the sparsity of the assignment problem due to the inherent
      properties of chromosome data. Furthermore, the auction algorithm also works when
      the chromosome data in a cell are incomplete due to the exclusion of overlapped
      or severely bent chromosomes, as often encountered in routine quality data.

PMID- 18048142
TI  - Optimal group testing algorithms with interval queries and their application to
      splice site detection.
AB  - Given an ordered set of n items and an unknown subset P of up to p positive
      elements, we want to identify P by asking the least number of queries 'does Q
      intersect P?' where Q must consist of consecutive elements. This Interval Group
      Testing problem arises in the context of splice site detection in genes. We study
      algorithms that operate in a few stages where queries chosen depending on
      previous answers, are performed in parallel. We obtain tight bounds for two-stage
      strategies. Finally, we get results for any number of stages and positives.

PMID- 18048143
TI  - Biomolecular autonomous solution of the Hamiltonian path problem via hairpin
      formation.
AB  - The Hamiltonian path problem is one of the famous hard combinatorial problems. We
      provide the first molecular-scale autonomous solution of the decision Hamiltonian
      path problem. It is based on the formation of secondary structures of DNA
      molecules.

PMID- 18048144
TI  - Temporal gene expression classification with regularised neural network.
AB  - This paper proposes regularised neural networks for characterisation of the
      multiple heterogeneous temporal dynamic patterns of gene expressions.
      Regularisation is developed to deal with noisy, high dimensional time course data
      and overfitting problems. We test the proposed model with a popular gene
      expression data. The model's performance is compared to other classification
      techniques, such as Nearest Neighbour, Support Vector Machine, and Self Organised
      Map. Results show that the proposed model can effectively capture the dynamic
      feature of gene expression temporal patterns despite the high noise levels, the
      highly correlated attributes, the overwhelming interactions, and other complex
      features typically present in microarray data.

PMID- 18048145
TI  - Protein-protein interaction and group testing in bipartite graphs.
AB  - The interactions between bait proteins and prey proteins are often critical in
      many biological processes, such as the formation of macromolecular complexes and
      the transduction of signals in biological pathways. Thus, identifying all protein
      protein interactions is an important task in those processes, which can be
      formulated as a group testing problem in bipartite graphs. In this paper, we take
      the advantages of the characteristics of bipartite graphs and present two
      nonadaptive algorithms for this problem. Furthermore, we illustrate a
      generalisation of our solution in a more general case.

PMID- 18048146
TI  - Protein secondary structure prediction by combining hidden Markov models and
      sliding window scores.
AB  - Instead of conformation states of single residues, refined conformation states of
      quintuplets are proposed to reflect conformation correlation. Simple hidden
      Markov models combined with sliding window scores are used to predict the
      secondary structure of a protein from its amino acid sequence. Since the length
      of protein conformation segments varies within a narrow range, we can ignore the
      duration effect of the length distribution. The window scores for residues are a
      window version of the Chou-Fasman propensities estimated under an approximation
      of conditional independency. Different window widths are examined, and the
      optimal width is found to be 17. A high accuracy of about 70% is achieved.

PMID- 18048147
TI  - Reconstructing phylogenetic trees of prokaryote genomes by randomly sampling
      oligopeptides.
AB  - In this paper, we propose a method for reconstructing phylogenetic trees of a
      given set of prokaryote organisms by randomly sampling relatively small
      oligopeptides of a fixed length from their complete proteomes. For each of the
      organisms, a vector of frequencies of the sampled oligopeptides is generated and
      used as a building block in reconstructing phylogenetic trees. By this procedure,
      multiple phylogenetic trees are created independently, and a consensus tree of
      those trees is created. We have applied our method to a set of 109 organisms,
      including 16 Archaea, 87 Bacteria, and 6 Eukarya, using around 10% of all the
      3,200,000 oligopeptides of length 5 in a reconstruction of a single phylogenetic
      tree. Our consensus tree agrees with the tree of Bergey's Manual in most of the
      basic taxa. In addition, they have almost the same quality as the trees of the
      same organisms reconstructed using all the 20<SUP align=right><SMALL>K</SMALL>
      oligopeptides of length K = 5 and 6 given by Qi et al. Thus we can conclude that,
      the frequencies of a relatively small number of oligopeptides of length 5, even
      if those oligopeptides are determined in a random method, has phylogenetic
      information almost equivalent to the frequencies of all the oligopeptides of
      length 5 or 6.

PMID- 18048148
TI  - Wavelet transformation and cluster ensemble for gene expression analysis.
AB  - This paper introduces a wavelet transformation and a cluster ensemble framework
      using graph theory for clustering gene expression data sets. The experiment
      results indicate that wavelet transformation and cluster ensemble approaches
      together yield better clustering results than the single best clustering
      algorithm on both synthetic and yeast gene expression data sets.

PMID- 18048149
TI  - Experimental analysis of a new algorithm for partial haplotype completion.
AB  - This paper deals with the computational problem of inferring complete information
      on haplotypes from haplotypes with missing data. This problem is one of the main
      issues in haplotyping, as the current DNA sequencing technology often produces
      haplotypes with missing bases and therefore the complete information on
      haplotypes has to be inferred through computational methods. In this paper, we
      propose a new algorithmic approach to the problem that assumes both the
      Coalescent and the Minimum Entropy models and we provide an experimental analysis
      relating it to the previously investigated approaches. In particular, the
      reconstruction of a perfect phylogeny from haplotypes with missing data is
      addressed.

PMID- 18048150
TI  - Predicting altered pathways using extendable scaffolds.
AB  - Many diseases, especially solid tumors, involve the disruption or deregulation of
      cellular processes. Most current work using gene expression and other high
      throughput data, simply list a set of differentially expressed genes. We propose
      a new method, PAPES (predicting altered pathways using extendable scaffolds), to
      computationally reverse-engineer models of biological systems. We use sets of
      genes that occur in a known biological pathway to construct component process
      models. We then compose these models to build larger scale networks that capture
      interactions among pathways. We show that we can learn process modifications in
      two coupled metabolic pathways in prostate cancer cells.

PMID- 18048151
TI  - Jumpstarting phylogenetic analysis.
AB  - Phylogenetic analysis is a central tool in studies of comparative genomics. When
      a new region of DNA is isolated and sequenced, researchers are often forced to
      throw away months of computation on an existing phylogeny of homologous sequences
      in order to incorporate this new sequence. The previously constructed trees are
      often discarded, and the researcher begins the search again from scratch. The
      jumpstarting algorithm uses trees from the prior search as a starting point for a
      new phylogenetic search. This technique drastically decreases search time for
      large data sets. This kind of analysis is necessary as researchers analyse tree
      of life size data sets.

PMID- 18048152
TI  - Discriminating TATA box from putative TATA boxes in plant genome.
AB  - The TATA box has been used successfully to identify a transcription start site
      (TSS) and thereby a promoter. Unfortunately, there are many substrings which fit
      the profile of a TATA box and such substrings are called putative TATA boxes. We
      have applied linear and non linear classifiers for discriminating TATA box from
      putative TATA boxes and have compared their performances. We have also
      investigated the influence of the length of the pair of sequences flanking a
      putative TATA box on the prediction accuracy. The techniques we have presented in
      this paper are general enough to be applicable to other domains or to other
      genomes.

PMID- 18048153
TI  - A rich analytical environment for flow cytometry experimental results.
AB  - Existing analysis tools for flow cytometry data offer specialised but limited
      functionality. This work presents advantages of combining the cytometer's data
      with sample-specific information. Data is loaded into a relational database,
      where the analyst can query based on sample characteristics such as species,
      gender, diet type or sample stain type.

PMID- 18048155
TI  - A novel approach to medical image compression.
AB  - As medical/biological imaging facilities move towards complete film-less imaging,
      compression plays a key role. Although lossy compression techniques yield high
      compression rates, the medical community has been reluctant to adopt these
      methods, largely for legal reasons, and has instead relied on lossless
      compression techniques that yield low compression rates. The true goal is to
      maximise compression while maintaining clinical relevance and balancing legal
      risk. This paper proposes a novel model-based compression technique that makes
      use of clinically relevant regions as defined by radiologists. Lossless
      compression is used in these clinically relevant regions, and lossy compression
      is used everywhere else.

PMID- 18048154
TI  - Computational modelling and simulation of the immune system.
AB  - We have developed a software system called SIMISYS that models and simulates
      aspects of the human immune system based on the computational framework of
      cellular automata. We model tens of thousands of cells as exemplars of the
      significant players in the functioning of the immune system, and simulate normal
      and simple disease situations by interpreting interactions among the cells.
      SIMISYS 0.3, the current version, models and simulates the innate and adaptive
      components of the immune system. The specific players we model are the
      macrophages, dendritic cells, neutrophils, natural killer cells, B cells, T
      helper cells, complement proteins and pathogenic bacteria.

PMID- 18048156
TI  - Protein sub-cellular localisation prediction by analysis of short-range residue
      correlations.
AB  - Sub-cellular localisation performs an important role in genome analysis. This
      paper describes a new residue-couple model using a support vector machine to
      predict the sub-cellular localisation of proteins. This new approach provides
      better predictions than the existing methods. The total prediction accuracies on
      Reinhardt and Hubbard's dataset reach 92.0% for prokaryotic protein sequences and
      86.9% for eukaryotic protein sequences with fivefold cross validation. For a new
      dataset with 8304 proteins located in eight sub-cellular locations, the total
      accuracy achieves 88.9%. Meanwhile, the model shows robust against N-terminal
      errors in the sequences.

PMID- 18048157
TI  - Homology search with binary and trinary scoring matrices.
AB  - Protein homology search can be accelerated with the use of bit-parallel
      algorithms in conjunction with constraints on the values contained in the scoring
      matrices. Trinary scoring matrices (containing only the values -1, 0, and 1)
      allow for significant acceleration without significant reduction in the receiver
      operating characteristic (ROC) score of a Smith-Waterman search. Binary scoring
      matrices (containing the values 0 and 1) result in some reduction in ROC score,
      but result in even more acceleration. Binary scoring matrices and five-bit
      saturating scores can be used for fast prefilters to the Smith-Waterman
      algorithm.

PMID- 18048158
TI  - RNA string kernels for RNAi off-target evaluation.
AB  - RNA interference (RNAi) is a posttranscriptional gene silencing mechanism used to
      study gene functions, knock down viral genes, and treat diseases therapeutically.
      However, an 'off-target effect' deteriorates its specificity and applicability.
      Complete off-target effects can only be characterised by examining each gene in a
      genome, which is too expensive to conduct experimentally and motivates a
      computational study. To simulate the sequence matching between an siRNA and its
      target mRNA allowing for mismatches, G-U wobbles and bulges, we propose string
      kernels and develop their efficient implementations for off-target detection. We
      evaluate RNAi specificities in Schizosaccharomyces pombe, Caenorhabdithis
      elegans, and human genomes.

PMID- 18048159
TI  - Statistical evaluation of NMR backbone resonance assignment.
AB  - This paper proposes a novel statistical evaluation model for automated protein
      NMR sequential resonance assignment. It can be bound to any assignment program
      and provides confidences for the whole output assignment and each individual
      mapping. A simulation study on a set of four proteins shows that the statistical
      evaluation results are informative.

PMID- 18048160
TI  - Magnitude and spatial orientation of the hydrophobic moments of multi-domain
      proteins.
AB  - The distributions of residue hydrophobicity for individual domains as well as for
      the aggregates of domains on a single chain have been found to exhibit well
      defined second-order hydrophobic moment profiles. This indicates that most of the
      domains do fold into a stable entity with a core composed predominantly of
      hydrophobic residues as well as a prevalence of hydrophobic residues at the
      interface between domains. A simple scoring function based upon the relative
      hydrophobic moment dipole orientations shows that 80% of the dipoles of adjacent
      domains point to each other, highlighting hydrophobic residue prevalence at the
      domain interfaces.

PMID- 18048162
TI  - Multiple testing in large-scale contingency tables: inferring patterns of pair
      wise amino acid association in beta-sheets.
AB  - This study examines the feasibility of using multiple testing procedures for an
      inference of independence of categories in each cell in contingency tables. In
      the simulation study, we compare the performance of various multiple testing
      procedures in a contingency table setup and demonstrate the relationship among
      the proportion of true null hypothesis, type I error, power, and false discovery
      rate. Finally, we apply the proposed methodology to identify the patterns of pair
      wise associations of amino acids involved in beta-sheet bridges in proteins. We
      identify a number of amino acid pairs that exhibit either strong or weak
      association.

PMID- 18048161
TI  - Handling missing DNA microarray data by kriging estimators.
AB  - Microarray gene expression data provide life science researchers with much more
      sensitive and detailed information about gene expression patterns than
      conventional methodologies for the purpose of facilitating gene recognition
      efforts. However, due to insufficient image resolution and noise generated during
      microarray experiments, gene expression matrices are frequently represented with
      missing elements. Methods for estimating missing microarray data are therefore
      needed to allow further analysis. In this paper, we present two kriging
      estimators for estimating missing values in DNA microarrays. These approaches can
      be useful for downstream analysis of microarray-based gene expression data.

PMID- 18048163
TI  - Phylogenetic analysis using complete signature information of whole genomes and
      clustered Neighbour-Joining method.
AB  - A new method called Complete Composition Vector (CCV), which is a collection of
      Composition Vectors (CV), is described to infer evolutionary relationships
      between species using their complete genomic sequences. Such a method bypasses
      the complexity of performing multiple sequence alignments and avoids the
      ambiguity of choosing individual genes for species tree construction. It is
      expected to effectively retain the rich evolutionary information contained in the
      whole genomic sequence. The method was applied to infer the evolutionary
      footprints for several datasets that have been previously studied. The final
      phylogenies were built by an improved clustered Neighbour-Joining method. The
      generated phylogenetic trees are highly consistent with taxonomy hierarchy and
      previous studies, with some biologically interesting disagreements.

PMID- 18048164
TI  - Identification of hair cycle-associated genes from time-course gene expression
      profile using fractal analysis.
AB  - Microarray technology permits one to monitor thousands of processes going on
      inside the cell. This tool has been used to study gene expression profiles
      associated with the hair-growth cycle. We provide a novel method called the
      fractal analysis method to identify hair-growth cycle associated genes from time
      course gene expression profiles. Fractal analysis is a much better method than
      the computational method used by Lin et al. (2004). The fractal dimension
      obtained by fractal analysis process also indicates the irregularity in hair
      growth pattern. The computational method used by Lin et al. (2004) was unable to
      make any inference about the hair-growth pattern.

PMID- 18048165
TI  - A grid-based pseudo-cache solution for MISD biomedical problems with high
      confidentiality and efficiency.
AB  - The complexity of most biomedical/bioinformatics problems requires efficient
      solutions using collaborative/parallel computing. One promising solution is to
      implement Grid computing, as an emerging new field called BioGrid. However, one
      of the most stringent requirements in such a Grid-based solution is data privacy.
      This paper presents a novel solution to provide the Confidentiality when using
      the Grid to efficiently solve MISD biomedical problems. It is called the Grid
      Based Pseudo-Cache (GBPC) solution. It is proved to have equal or better
      performance than traditional MIMD solution. Via case studies our theories are
      validated in practice, and the data dependence is also addressed.

PMID- 18048166
TI  - Finding functional promoter motifs by computational methods: a word of caution.
AB  - The standard practice in the analysis of promoters is to select promoter regions
      of convenient length. This may lead to false results when searching for
      Transcription Factor Binding Sites (TFBSs), since the sequences may contain
      coding segments. In such cases, motif detection may single out motifs from the
      coding regions. The mapping of TFBSs to promoters may result in a misleading
      picture of 'promoter' content. We illustrate these issues using the example of
      histones H2A and H2B and show how such analysis could be misleading if care is
      not exercised to eliminate coding regions from the presumed promoter sequences.

PMID- 18048167
TI  - Memory efficient alignment between RNA sequences and stochastic grammar models of
      pseudoknots.
AB  - Stochastic Context-Free Grammars (SCFG) has been shown to be effective in
      modelling RNA secondary structure for searches. Our previous work (Cai et al.,
      2003) in Stochastic Parallel Communicating Grammar Systems (SPCGS) has extended
      SCFG to model RNA pseudoknots. However, the alignment algorithm requires O(n4)
      memory for a sequence of length n. In this paper, we develop a memory efficient
      algorithm for sequence-structure alignments including pseudoknots. This new
      algorithm reduces the memory space requirement from O(n4) to O(n2) without
      increasing the computation time. Our experiments have shown that this novel
      approach can achieve excellent performance on searching for RNA pseudoknots.

PMID- 18048168
TI  - Probabilistic models for biological sequences: selection and Maximum Likelihood
      estimation.
AB  - Probabilistic models for biological sequences (DNA and proteins) are frequently
      used in bioinformatics. We describe statistical tests designed to detect the
      order of dependency among elements of the sequence and to select the most
      appropriate probabilistic model for an experimental biological sequence. For a
      model of given type, the independence model, the first-order Markov chain and the
      hidden Markov model (HMM), we derive the uniform lower bound for the rate of
      decay for the errors of the maximum likelihood (ML) estimates of the model
      parameters and, subsequently, the uniform confidence intervals for the
      parameters.

PMID- 18048169
TI  - GE-Miner: integration of cluster ensemble and text mining for comprehensive gene
      expression analysis.
AB  - Generating high quality gene clusters and identifying the underlying biological
      mechanism of the gene clusters are the important goals of clustering gene
      expression analysis. Based on this consideration, we design and develop a unified
      system Gene Expression Miner (GE-Miner) by integrating cluster ensemble, text
      clustering and multidocument summarisation and provide an environment for
      comprehensive gene expression data analysis. Experimental results demonstrate
      that our systems can obtain high quality clusters and provide concise and
      informative textual summary for the gene clusters.

PMID- 18048170
TI  - An algorithmic approach for static and dynamic gesture recognition utilising
      mechanical and biomechanical characteristics.
AB  - We propose a novel approach for recognising static and dynamic hand gestures by
      analysing the raw data streams generated by the sensors attached to the human
      hands. We utilise the concept of 'range of motion' in the movement of fingers and
      exploit this characteristic to analyse the acquired data for recognising hand
      signs. Our approach for hand gesture recognition addresses two major problems:
      user-dependency and device-dependency. Furthermore, we show that our approach
      neither requires calibration nor involves training. We apply our approach for
      recognising American Sign Language (ASL) signs and show that more than 75%
      accuracy in sign recognition can be achieved.

PMID- 18048171
TI  - Efficient evaluation of radial queries using the target tree.
AB  - We propose a novel indexing structure, called the target tree, which is designed
      to answer a new type of spatial query, called the radial query. A radial query
      finds all objects in the spatial data set that intersect with line segments
      emanating from a single target point. Many biomedical applications use radial
      queries, including neurosurgical planning. A target tree uses a regular
      hierarchical decomposition of space using wedge shapes that emanate from the
      target point. We compare the target tree with the R*-tree and quadtree, and show
      that the target tree is significantly faster than these methods.

PMID- 18048172
TI  - On mining micro-array data by Order-Preserving Submatrix.
AB  - We study the problem of pattern-based subspace clustering which is clustering by
      pattern similarity finds objects that exhibit a coherent pattern of rises and
      falls in subspaces. Applications of pattern-based subspace clustering include DNA
      micro-array data analysis. Our goal is to devise pattern-based clustering methods
      that are capable of: discovering useful patterns of various shapes, and
      discovering all significant patterns. Our approach is to extend the idea of Order
      Preserving Submatrix (OPSM). We devise a novel algorithm for mining OPSM, show
      that OPSM can be generalised to cover most existing pattern-based clustering
      models and propose a number of extensions to the original OPSM model.

PMID- 18048173
TI  - Finding molecular complexes through multiple layer clustering of protein
      interaction networks.
AB  - Clustering protein-protein interaction networks (PINs) helps to identify
      complexes that guide the cell machinery. Clustering algorithms often create a
      flat clustering, without considering the layered structure of PINs. We propose
      the MULIC clustering algorithm that produces layered clusters. We applied MULIC
      to five PINs. Clusters correlate with known MIPS protein complexes. For example,
      a cluster of 79 proteins overlaps with a known complex of 88 proteins. Proteins
      in top cluster layers tend to be more representative of complexes than proteins
      in bottom layers. Lab work on finding unknown complexes or determining drug
      effects can be guided by top layer proteins.

PMID- 18048174
TI  - Efficient composite pattern finding from monad patterns.
AB  - Automatically identifying frequent composite patterns in DNA sequences is an
      important task in bioinformatics, especially when all the basic elements (or
      monad patterns) of a composite pattern are weak. In this paper, we compare one
      straightforward approach to assemble the monad patterns into composite patterns
      to two other rather complex approaches. Both our theoretical analysis and
      empirical results show that this overlooked straightforward method can be several
      orders of magnitude faster. Furthermore, different from the previous
      understandings, the empirical results show that the runtime superiority among the
      three approaches is closely related to the insignificance of the monad patterns.

PMID- 18048175
TI  - Computer simulation of intracardiac potential with whole-heart model.
AB  - Computer simulation of intracardiac potentials was performed based on a whole
      heart model, emphasising applications to Electrophysiology Study (EPS) and
      catheter ablation. A numerical method was proposed based on a volume conductor
      model with multiple interfaces and piecewise homogeneity. A model of a normal
      heart and a model of Wolff-Parkinson-White (WPW) Syndrome with a right free-wall
      Accessory Pathway (AP) were employed to simulate intracardiac electrograms. The
      study was validated by comparing the simulated electrograms with those in
      catheter-based EPS and ablations. Applying whole-heart modelling to the EPS and
      ablation is regarded as a new direction of electrocardiologic forward problem.

PMID- 18048176
TI  - A parallel implementation of 2-D/3-D image registration for computer-assisted
      surgery.
AB  - Image registration is a technique usually used for aligning two different images
      taken at different times and/or from different viewing points. A key challenge
      for medical image registration is to minimise computation time with a small
      alignment error in order to realise computer-assisted surgery. In this paper, we
      present the design and implementation of a parallel two-dimensional/three
      dimensional (2-D/3-D) image registration method for computer-assisted surgery.
      Our method exploits data parallelism and speculative parallelism, aiming at
      making computation time short enough to carry out registration tasks during
      surgery. Our experiments show that exploiting both parallelisms reduces
      computation time on a cluster of 64 PCs from a few tens of minutes to less than a
      few tens of seconds, a clinically compatible time.

PMID- 18048177
TI  - Rotational and translational alignment errors in 3D reconstruction of virus
      structures at high resolution.
AB  - The 3D reconstruction of virus structures at high resolution using CryoTEM data
      requires a very accurate rotational and translational alignment of individual
      views obtained experimentally. We discuss the geometrical foundations and the
      computational problems raised by rotational and translational alignment. We also
      outline the basic ideas for CTF correction.

PMID- 18048178
TI  - Concurrent numerical simulation of flow and blood clotting using the lattice
      Boltzmann technique.
AB  - In this paper, we describe a novel approach for a concurrent numerical simulation
      of the unsteady flow within an idealised stenosed artery and a simplified blood
      clotting process based on a residence time model. The applied numerical scheme is
      the lattice Boltzmann technique, which proved to be highly efficient particularly
      for transient flows and complex or varying geometries.

PMID- 18048179
TI  - MESSM: a framework for protein fold recognition using neural networks and support
      vector machines.
AB  - A new framework (called MESSM) for protein fold recognition with three key
      features is proposed in this paper. Being tested on three benchmark problems, the
      results show that the MESSM has a comparable performance on fold recognition to
      those more computational intensive, energy potential based fold recognition
      models. The MESSM leads to a better performance on alignment accuracy. The MESSM
      presents a new way to develop an efficient tool for protein fold recognition.

PMID- 18048180
TI  - High-speed multiple sequence alignment on a reconfigurable platform.
AB  - Progressive alignment is a widely used approach to compute multiple sequence
      alignments (MSAs). However, aligning several hundred sequences by popular
      progressive alignment tools requires hours on sequential computers. Due to the
      rapid growth of sequence databases biologists have to compute MSAs in a far
      shorter time. In this paper we present a new approach to MSA on reconfigurable
      hardware platforms to gain high performance at low cost. We have constructed a
      linear systolic array to perform pairwise sequence distance computations using
      dynamic programming. This results in an implementation with significant runtime
      savings on a standard FPGA.

PMID- 18048181
TI  - PRec-I-DCM3: a parallel framework for fast and accurate large-scale phylogeny
      reconstruction.
AB  - Accurate reconstruction of phylogenetic trees often involves solving hard
      optimisation problems, particularly the Maximum Parsimony (MP) and Maximum
      Likelihood (ML) problems. Various heuristics yield good results for these
      problems within reasonable time only on small datasets. This is a major
      impediment for large-scale phylogeny reconstruction. Roshan et al. introduced Rec
      I-DCM3, an efficient and accurate meta-method for solving the MP problem on large
      datasets of up to 14,000 taxa. We improve the performance of Rec-I-DCM3 via
      parallelisation. The experiments demonstrate that our parallel method, PRec-I
      DCM3, achieves significant improvements, both in speed and accuracy, over its
      sequential counterpart.

PMID- 18048182
TI  - Numerical solutions of a master equation for protein folding kinetics.
AB  - The numerical solution of a master equation involves the calculation of
      eigenpairs for the corresponding transition matrix. In this paper, we
      computationally study the folding rate for a kinetics problem of protein folding
      by solving a large-scale eigenvalue problem. Three numerical methods, the
      implicitly restarted Arnoldi, the Jacobi-Davidson, and the QR methods are applied
      to solve the corresponding large-scale eigenvalue problem of the transition
      matrix of the master equation. Comparison among three methods is performed in
      terms of the computational efficiency. It is found that the QR method demands
      tremendous computing resource when the length of sequence L > 10 due to the
      extremely large size of matrix and CPU time limitation. The Jacobi-Davidson
      method may encounter convergence issues, for some testing cases with L > 9. Among
      the three solution methods the implicitly restarted Arnoldi method is suitable
      for solving the problem. Numerical examples with various residues are
      investigated.

PMID- 18048183
TI  - Optimised fine and coarse parallelism for sequence homology search.
AB  - New biological experimental techniques are continuing to generate large amounts
      of data using DNA, RNA, human genome and protein sequences. The quantity and
      quality of data from these experiments makes analyses of their results very time
      consuming, expensive and impractical. Searching on DNA and protein databases
      using sequence comparison algorithms has become one of the most powerful
      techniques to better understand the functionality of particular DNA, RNA, genome,
      or protein sequence. This paper presents a technique to effectively combine fine
      and coarse grain parallelism using general-purpose processors for sequence
      homology database searches. The results show that the classic Smith-Waterman
      sequence alignment algorithm achieves super linear performance with proper
      scheduling and multi-level parallel computing at no additional cost.

PMID- 18048184
TI  - Supervised classification of protein structures based on convex hull
      representation.
AB  - One of the central problems in functional genomics is to establish the
      classification schemes of protein structures. In this paper the relationship of
      protein structures is uncovered within the framework of supervised learning.
      Specifically, the novel patterns based on convex hull representation are firstly
      extracted from a protein structure, then the classification system is constructed
      and machine learning methods such as neural networks, Hidden Markov Models (HMM)
      and Support Vector Machines (SVMs) are applied. The CATH scheme is highlighted in
      the classification experiments. The results indicate that the proposed supervised
      classification scheme is effective and efficient.

PMID- 18048185
TI  - Decoding algorithms in pooling designs with inhibitors and error-tolerance.
AB  - Pooling designs are used in DNA library screening to efficiently distinguish
      positive from negative clones, which is fundamental for studying gene functions
      and many other biological applications. One challenge is to design decoding
      algorithms for determining whether a clone is positive based on the test outcomes
      and a binary matrix representing the pools. This is more difficult in practice
      due to errors in biological experiments. More challenging still is a third
      category of clones called 'inhibitors' whose effect is to neutralise positives.
      We present a novel decoding algorithm identifying all positive clones in the
      presence of inhibitors and experimental errors.

PMID- 18048186
TI  - Structural Risk Minimisation based gene expression profiling analysis.
AB  - For microarray based cancer classification, feature selection is a common method
      for improving classifier generalisation. Most wrapper methods use cross
      validation methods to evaluate feature sets. For small sample problems like
      microarray, however, cross validation methods may overfit the data. In this
      paper, we propose a Structural Risk Minimisation (SRM) based method for gene
      selection in cancer classification. SRM principle allows for reducing the
      probable bound on generalisation error and thus avoids overfitting problems. The
      experimental results show that the proposed method produces significantly better
      performance than general wrapper methods that use cross validations.

PMID- 18048187
TI  - Modelling gene functional linkages using yeast microarray data.
AB  - Understanding how genes are functionally related requires efficient algorithms to
      model networks from expression data. We report a heuristic search algorithm
      called Two-Level Simulated Annealing (TLSA) that is more likely to find the
      global optimal network structure compared to conventional simulated annealing and
      other searching schemes. We have applied this method to search for a global
      optimised network structure from a synthetic data set and an expression data set
      of S. cerevisiae mutants. We have achieved better precision and recall compared
      to other searching algorithms and are able to map relationships more accurately
      among functionally-linked genes.

PMID- 18048188
TI  - Analysing the performance of personal computers based on Intel microprocessors
      for sequence aligning bioinformatics applications.
AB  - Aligning specific sequences against a very large number of other sequences is a
      central aspect of bioinformatics. With the widespread availability of personal
      computers in biology laboratories, sequence alignment is now often performed
      locally. This makes it necessary to analyse the performance of personal computers
      for sequence aligning bioinformatics benchmarks. In this paper, we analyse the
      performance of a personal computer for the popular BLAST and FASTA sequence
      alignment suites. Results indicate that these benchmarks have a large number of
      recurring operations and use memory operations extensively. It seems that the
      performance can be improved with a bigger L1-cache.

PMID- 18048189
TI  - A novel stationary wavelet denoising algorithm for array-based DNA Copy Number
      data.
AB  - High-throughput microarrays have recently been developed to detect DNA Copy
      Number (DCN) aberrations. The resulting DCN data is often very noisy. Previous
      denoising methods proposed for DCN data assumed uniform spacing between adjacent
      probes, which is not true and can potentially result in erroneous output. To
      address this issue, we developed a novel stationary wavelet denoising scheme for
      DCN data. Empirical results on synthetic data showed that our method outperformed
      the best previous method by 4.612.7% in terms of the root mean squared error.
      Experiments on a real data set also confirmed the applicability of our method.

PMID- 18048190
TI  - Prediction of the disulphide bridges in proteins using SVM.
AB  - Disulphide bonds link distant portions of protein chains and provide strong
      structural constraints in the form of long-range interactions. Prediction and
      knowledge of disulphide bond connectivity is important in reducing the search
      space of protein conformation. In this research, we present an effective way to
      predict disulphide bridges by Support Vector Machine (SVM). The SVM encoding was
      based on experimental results on the binding motifs of protein disulphide
      isomerases. The physical-chemical characteristics of the flanking sequences and
      the linear distance between the concerned cysteine pairs were also included in
      the encoding. An overall pair wise accuracy of 92% was obtained for the SP39
      dataset.

PMID- 18048191
TI  - Is the protein folding an aim-oriented process? Human haemoglobin as example.
AB  - The model for protein folding (in silico) simulation is presented. Three steps
      have been implemented: early stage folding based on the backbone conformation;
      hydrophobic collapse based on the fuzzy-oil-drop model; aim-oriented structure
      modification by the function-related ligand. The model has been verified taking
      alpha and beta haemoglobin chains as examples to fold them in two different
      conditions: with and without haem being present in the folding environment. The
      presence of haem and its participation in the folding simulation led to the
      structure more similar to the crystal one. It suggests that the haem presence
      directs the folding process towards the function-related structure.

PMID- 18048192
TI  - An ontology-based framework for bioinformatics workflows.
AB  - The proliferation of bioinformatics activities brings new challenges - how to
      understand and organise these resources, how to exchange and reuse successful
      experimental procedures, and to provide interoperability among data and tools.
      This paper describes an effort toward these directions. It is based on combining
      research on ontology management, AI and scientific workflows to design, reuse and
      annotate bioinformatics experiments. The resulting framework supports automatic
      or interactive composition of tasks based on AI planning techniques and takes
      advantage of ontologies to support the specification and annotation of
      bioinformatics workflows. We validate our proposal with a prototype running on
      real data.

PMID- 18048193
TI  - A case study of integrating protein interaction data using semantic web
      technology.
AB  - We describe a new ontology-driven semantic data integration approach for post
      genome biology studies. Here, a view-based global schema can be automatically
      generated by merging RDF schemas from local databases. The semantic inconsistency
      of the merged schema is resolved by the creation of 'RDF ontology maps'. Data
      querying capability is accomplished with a virtual data repository, in which a
      D2RQ-based 'relational-to-RDF' map is developed to link schema to the relational
      database backend. With sample RDQL queries, we demonstrate that our approach
      significantly simplifies the retrieval of human protein interaction data from
      different databases containing hundreds of thousands of records.

PMID- 18048194
TI  - The (my)Grid ontology: bioinformatics service discovery.
AB  - (my)Grid supports in silico experiments in the life sciences, enabling the design
      and enactment of workflows as well as providing components to assist service
      discovery, data and metadata management. The (my)Grid ontology is one component
      in a larger semantic discovery framework for the identification of the highly
      distributed and heterogeneous bioinformatics services in the public domain. From
      an initial model of formal OWL-DL semantics throughout, we now adopt a spectrum
      of expressivity and reasoning for different tasks in service annotation and
      discovery. Here, we discuss the development and use of the (my)Grid ontology and
      our experiences in semantic service discovery.

PMID- 18048195
TI  - A database ontology for signal transduction pathways.
AB  - Ontologies are one of the key technologies for data integration and meta
      databases, by connecting databases at a semantical level. Still, the database has
      to be connected to the ontology and vice versa. To achieve this, we propose a two
      step process. First, we automatically generate an ontology directly from the
      database schema. Next, we annotate this with concepts from a domain specific
      ontology. We demonstrate this for signal transduction pathways, which describe
      how cells can react to external stimuli. In this paper we present our mapping of
      database schemas to ontologies and describe how these ontologies can be enriched
      by semantical information.

PMID- 18048196
TI  - A pragmatic approach to mapping the open biomedical ontologies.
AB  - There has been a large increase in the number of ontologies that have been
      introduced by the biomedical community in recent years. To maximise their
      potential, there is an urgent need for a mechanism to build interoperability
      between ontologies developed by different groups. While identifying and linking
      related concepts is of obvious importance, it is also essential to analyse how
      ontologies as a whole overlap and can be clustered. This paper explores
      overlapping relationships in the Open Biomedical Ontologies (OBO) and provides an
      interoperability framework called InterOBO for sharing biomedical knowledge
      across OBO communities.

PMID- 18048197
TI  - Modelling concepts and database implementation techniques for complex biological
      data.
AB  - Biological data such as protein structure and function, DNA sequences, and
      metabolic pathways require conceptual modelling characteristics that are not
      available in the widely used Entity-Relationship (ER) model and its variants,
      such as the Enhanced-Entity Relationship (EER) model. In particular, three
      constructs that occur frequently in bioinformatics data are ordered
      relationships, functional processes, and 3-dimensional (3D) structures. In this
      paper, we suggest a solution to this problem, requiring only minimal changes to
      the EER model by introducing specialised formal relationships for ordering,
      processes and molecular spatial structure. We show how these new concepts can be
      implemented in relational databases.

PMID- 18048198
TI  - Enhanced semantic access to the protein engineering literature using ontologies
      populated by text mining.
AB  - The biomedical literature is growing at an ever-increasing rate, which pronounces
      the need to support scientists with advanced, automated means of accessing
      knowledge. We investigate a novel approach employing description logics (DL)
      based queries made to formal ontologies that have been created using the results
      of text mining full-text research papers. In this paradigm, an OWL-DL ontology
      becomes populated with instances detected through natural language processing
      (NLP). The generated ontology can be queried by biologists using DL reasoners or
      integrated into bioinformatics workflows for further automated analyses. We
      demonstrate the feasibility of this approach with a system targeting the protein
      mutation literature.

PMID- 18048199
TI  - Biomedical ontology improves biomedical literature clustering performance: a
      comparison study.
AB  - Document clustering has been used for better document retrieval and text mining.
      In this paper, we investigate if a biomedical ontology improves biomedical
      literature clustering performance in terms of the effectiveness and the
      scalability. For this investigation, we perform a comprehensive comparison study
      of various document clustering approaches such as hierarchical clustering
      methods, Bisecting K-means, K-means and Suffix Tree Clustering (STC). According
      to our experiment results, a biomedical ontology significantly enhances
      clustering quality on biomedical documents. In addition, our results show that
      decent document clustering approaches, such as Bisecting K-means, K-means and
      STC, gains some benefit from the ontology while hierarchical algorithms showing
      the poorest clustering quality do not reap the benefit of the biomedical
      ontology.

PMID- 18048200
TI  - Electronic home healthcare: concepts and challenges.
AB  - Telemedicine in homecare--also known as telehomecare (THC) or electronic home
      healthcare--uses telecommunication and videoconferencing technologies to enable a
      healthcare provider at the clinical site to communicate with patients in their
      home. Such an interaction is called a "virtual visit". Numerous applications are
      utilising commercially available monitoring devices and the internet to enable
      home-based disease management and monitoring. Prior to the implementation of
      telehomecare applications, one needs to address issues of accessible design,
      privacy and confidentiality of medical data, and reimbursement. The evaluation of
      such applications should focus on their impact on clinical processes, outcomes,
      cost of and access to care, patients' and providers' acceptance. This paper
      provides an overview of the concepts and challenges of electronic home
      healthcare.

PMID- 18048201
TI  - Business evolution or revolution? Mail-order pharmacies in Germany.
AB  - It is an interesting detail of the present reform of national public health
      service in Germany that mail-order and internet pharmacies will be founded in
      future as new (e-commerce) business models. Main points of conceivable business
      systems can be characterised as well as critical success factors. No potential
      participant can ever have all the necessary resources and competences to
      implement a competitive business system without external support. This is why
      cooperation seems to be a useful tool for competence management. The Resource
      based View will serve as theoretical background for analysis. The required and
      available competences of conceivable players can be identified. Features of
      resources can be described that recommend special types of cooperation with the
      intention of establishing and operate a business system. Especially German and
      international pharmaceutical wholesalers can be identified as conceivable
      "parents" of mail-order pharmacies in the future.

PMID- 18048202
TI  - E-health and assurance: curing hospital websites.
AB  - Hospital websites are becoming an industry standard as patients (consumers) and
      health professionals use web resources for information, research, and
      communication. Industry predictions focused on future e-hospitals that would
      integrate all stakeholders in a seamless network allowing data to be shared. This
      paper investigates web assurance strategies implemented by hospitals in the
      design of their websites. The protection of critical infrastructure and
      information is crucial to the success of the web assurance strategy. The study
      reviewed a sample of 100 premier hospital websites. Results show little progress
      in the goal of making the website a fully functional unit of the hospital.
      Current sites are limited in scope and have become more selective in their
      provision of information in light of new HIPAA regulations.

PMID- 18048203
TI  - Barriers to e-health business processes.
AB  - This paper builds from recent case study research in commercial organisations to
      develop the hypothesis that many of the barriers to e-health processes are
      similar to those encountered by commercial businesses. The paper reports findings
      from a case study within the pathology department of a UK National Health Service
      (NHS) Trust. The NHS has a risk-averse culture where many individuals practice
      defensive behaviour and there are deeply embedded working practices. The paper
      suggests that if the NHS is to seize the opportunities offered by substantial new
      investments in e-health systems that utilise internet-based ICTs, greater effort
      needs to be made to understand and address the socio-cultural factors affecting
      the UK healthcare system.

PMID- 18048204
TI  - A wireless trust model for healthcare.
AB  - In today's context of escalating costs, managed care, regulations such as the
      Health Insurance Portability and Accountability Act (HIPAA) and a technology
      savvy patient, the healthcare industry can no longer be complacent regarding
      embracing technologies to enable better, more effective and efficient practice
      management. In such an environment, many healthcare organisations are turning to
      m-commerce or wireless solutions. These solutions, in particular the mobile
      electronic patient record, have many advantages over their wired counterparts,
      including significant cost advantages, higher levels of physician acceptance,
      more functionalities as well as enabling easy accessibility to healthcare in
      remote geographic regions, however, they also bring with them challenges of their
      own. One such major challenge is security. To date, few models exist that help
      establish an appropriate framework, in the context of wireless in healthcare, in
      which to understand and evaluate all the security issues let alone facilitate the
      development of systematic and robust solutions. Our paper addresses this need by
      outlining an appropriate mobile trust model for such a scenario in healthcare
      organisations.

PMID- 18048205
TI  - Using internet GIS technology for early warning, response and controlling the
      quality of the public health sector.
AB  - Recent EU and Greek Government legislation highlights the need for the
      modernisation of the public health management system and the improvement of the
      overall health of EU citizens. In addition, the effusion of epidemics even in
      developed countries makes the need for the enhancement of public health services
      imperative. In order to best confront the above-described challenges, the
      National Technical University of Athens, in cooperation with the Greek Ministry
      of Health and Welfare and the European Commission (EC), designed and developed an
      integrated public health information network, named GEPIMI (Integrated
      Geographical System for EPIdemiological and other Medical Information), in the
      framework of a three-year pilot project. This pilot project, funded by Greek
      Ministry of Health and Welfare and the EC supported the Programme INTERREG II to
      establish an advanced and integrated web-based information system that can
      process and move information in real time, allowing public health authorities to
      monitor events at hundreds or thousands of public health facilities at once. The
      system is established among hospitals, primary healthcare authorities and health
      agents in Greece, Bulgaria, Albania, Fyrom, and Turkey. The project aims at
      demonstrating the best practices, prospects, applications and high potential of
      Telematics Healthcare Networks in Europe, with a view to promoting cooperation
      and interconnection between European communities in the field of Telematics
      Healthcare Applications. The GEPIMI System, implemented via an innovative web
      based system, constitutes a replication of a highly effective mechanism. It
      incorporates state-of-the-art technologies such as Geographic Information Systems
      (G.I.S.), web based databases, GPS, and Smart Card Technology and supports a
      variety of health-related web applications including early warning and response
      of epidemics, remote management of medical records, seamless healthcare coverage,
      comprehensive statistical analysis of data, decision-making procedures, inter
      communication between international scientific fora and other.

PMID- 18048206
TI  - Evolving medical informatics: from diagnosis to prognosis.
AB  - The application of computers to the medical field is not new; however, the
      leisurely rate of integration has left the medical field in the "dark ages" of
      technology. A brief overview of how computers and technology have been used in
      the medical field is necessary to understand medical computer science. The recent
      advances of the internet infrastructure and personal computing, combined with the
      ubiquitous nature of their application, have allowed everyday people to
      incorporate technology into their daily routine. Only a few have ventured into
      the ill-defined world of medical computer science, some with great success,
      others with hopeful failures. The purpose of this paper is to sustain the recent
      advances in medical computer science and to provide support for shifting the
      focus of medical technology from diagnosis towards patient prognosis.

PMID- 18048207
TI  - Electronic transmission of prescriptions: towards realising the dream.
AB  - The UK National Health Service (NHS) is about to commence upon major
      computerisation of its processes as part of a government plan of modernisation.
      One of these is the Electronic Transmission of Prescription (ETP). To achieve
      success it is important to know what benefits are expected from the new system
      and what barriers to adoption the systems will face. This paper reviews
      substantial ETP published material, and identifies 17 issues that need to be
      addressed. These issues are categorised under four major headings of
      stakeholders, cost, technology, and current process and practice, and are then
      further classified as positive or negative influences on the project's success.
      Many of these influences will be common to most of the computerisation projects
      to be undertaken by the NHS, and therefore this paper has wider applicability
      than ETP.

PMID- 18048208
TI  - Economic evaluation of telemedicine for a remotely located population: the case
      of two Greek islands.
AB  - A 12-month trial with telemedicine was conducted at two remote health centres
      located on Greek Islands, namely Lemnos and Skyros, where combat units of the
      Greek Airforce are situated. The units' medical services are supported by the
      251st Central Hospital of the Greek Airforce in Athens, via a PC-based ISDN
      videoconferencing link, connected at 384 Kbps. Thirty-eight patients were
      recruited for the trial. A cost minimisation analysis was undertaken, for
      comparing the costs of telemedicine to those of hospital referrals, where
      patients from remote areas travelled to the hospital for consultation. The cost,
      per patient, for remote consultation was calculated to be 203.5 euro compared to
      270 euro for referrals. These results proved to be relatively robust after being
      tested with a sensitivity analysis. The benefits and cost savings would be
      greater in the case of islands or other such remote communities, where patients
      have to travel long distances either for hospitalisation or for specialist
      consultations. However, it should be noted that the cost of telemedicine depends
      on the number of patients served in the isolated area.

PMID- 18048209
TI  - Mapping e-health strategies: thinking outside the traditional healthcare box.
AB  - E-health has evolved and emerged in many forms; for instance, prescription
      refills, appointment scheduling, online billing, online medical records, and
      patient provider communications. Among other marketable e-health strategic
      applications, the use of e-health information has proliferated and has been
      presented in the form of content-only health gateways, physician directories,
      physician-only sites, and online pharmacies. The adoption of the web as an e
      health medium has caused both traditional and e-healthcare providers to rethink
      and experiment with innovative ways of providing healthcare services. The e
      providers who can effectively market themselves on the web will have a distinct
      advantage. At this time, a lot of education appears to be needed in this field in
      order to ensure that key players in this arena are contributing to the growth and
      success of e-health. In this paper, we present a general framework for mapping e
      health strategies based on e-health business structures and their value
      proposition. Such e-health systems may be designed to meet the needs of e
      stakeholders and for gaining competitive advantages. We believe that by opening
      up this line of discussion, it will provide future-orientated healthcare
      executives and entrepreneurs with useful insights into feasible e-health
      strategic solutions and their commercial potentials.

PMID- 18048210
TI  - Establishing strategic alliance among hospitals through SAIS: a case study in
      Taiwan.
AB  - Due to a reformed healthcare insurance system and a gradually decreasing public
      affairs' budget by the government year by year, Central Taiwan Office (CTO), the
      Department of Health (DOH) in Taiwan, initiated a strategic alliance project of
      the hospitals subordinated to the DOH in November, 2001. This project was a five
      year plan with an attempt to expand and develop three more strategic alliances
      covering the northern, southern and eastern regions of Taiwan respectively.
      Through a cooperative system, such an alliance allows the following: resource
      sharing, technique collaboration, marketing affiliations and so on. In order to
      decrease operation management costs and improve the quality of service at
      hospitals, the strategic alliance practice is supported by IS. We call this
      alignment the IS-enabled strategic alliance. All the IS-enabled functions are
      supported by the Strategic Alliance Information System (SAIS). In this article,
      the SAIS developed by the CTO of the DOH is introduced.

PMID- 18048211
TI  - An examination of selected drug availability at online pharmacies.
AB  - According to the literature, prescription cost and convenience are generally
      regarded as the most important reasons for buying online. This study examines the
      availability of selected prescription drugs at some of the online pharmacies in
      the USA. Specifically, the drugs examined are among the ten most often prescribed
      by physicians.

PMID- 18048212
TI  - E-health versus KM-based health: a dilemma in researchers' minds.
AB  - Over the past several years, there have been intensive discussions about the
      importance of Knowledge Management (KM) within our society. As we are moving into
      an era of "knowledge capitalism", the management of knowledge is promoted as an
      important and necessary factor for organisational survival and maintenance of
      competitive strength. During the last 15 years, KM has changed from one
      generation to the next through constant improvements and new perspectives. Many
      researchers have presented methodologies, frameworks, technologies and have
      discussed various KM theoretical and practical issues in several sectors,
      including healthcare. E-health and KM-based health are still in an early state of
      evolution, and it is only recently that researchers decided to intensify their
      efforts in these fields. In this context, this paper aims to review the current
      status quo, analyse key issues to which researchers should pay attention and
      contribute to researchers' dilemma solving about where future research should be
      focused.

PMID- 18048213
TI  - A framework for assessing e-health preparedness.
AB  - Whilst healthcare is the biggest service industry on the globe, it has yet to
      realise the full potential of the e-business revolution in the form of e-health.
      This is due to many reasons including the fact that the healthcare industry is
      faced with many complex challenges in trying to deliver cost-effective, high
      value, accessible healthcare and has traditionally been slow to embrace new
      business techniques and technologies. Given that e-health, to a great extent, is
      a macro level concern that has far reaching micro level implications, this paper
      firstly develops a framework to assess a country's preparedness with respect to
      embracing e-health (the application of e-commerce to healthcare) and from this an
      e-health preparedness grid to facilitate the assessment of any e-health
      initiative. Taken together, the integrative framework and preparedness grid
      provide useful and necessary tools to enable successful e-health initiatives to
      ensue by helping country and/or an organisation within a country to identify and
      thus address areas that require further attention in order for it to undertake a
      successful e-health initiative.

PMID- 18048214
TI  - Setting up a Wireless Local Area Network (WLAN) for a healthcare system.
AB  - WLAN can help the medical professionals to improve their working efficiency and
      reduce medical errors. In this paper, the important issues of deploying WLAN in
      hospitals are discussed. It gives a comprehensive overview of how to set up the
      mobility, Quality of Service (QoS) and security of the WLAN for a healthcare
      system. IEEE 802.11e standard and the Health Insurance Portability and
      Accountability ACT (HIPAA) regulations are discussed and some suggestions are
      given to meet the specific requirements of a healthcare environment.

PMID- 18048215
TI  - Getting from A to C: lifecycle lessons for e-health deployment.
AB  - The 35-year history of continuous development of hospital information systems and
      the current efforts to develop an electronic health record in outpatient settings
      suggest a lifecycle that must take place before electronic technology is adopted
      in the highly decentralised US healthcare system. This six-stage lifecycle,
      called the ABCs of change, involves Acceptance of the need for change, Alignment
      of the actors to fulfil that need, Breadboard development of the desired,
      integrated system, a Blueprint for the system to be commercialised, Configuration
      methods for adapting the system to individual provider and patient needs, and
      Capital sources for the desired change. This article shows how that six-stage
      model is relevant to understanding prior development attempts and how current
      efforts to bring electronic health records to small, primary-care practices
      follow it. We conclude that it is a useful model for insight and for future
      planning.

PMID- 18048216
TI  - How organisational politics explain IS implementation outcomes in hospitals.
AB  - In the healthcare sector, the use of computer-based information systems (IS)
      offers a lot of new challenges. However, despite the compelling potential of the
      new technology, implementing IS in practice often turns out to be a pitfall.
      Concretely, the introduction of information systems, especially in hospitals,
      does not often come on time and on budget, nor does it always accomplish the
      initial organisational goals. We postulate that implementation failures occur to
      a great extent because organisations do not adequately manage the politics of
      information; especially healthcare organisations as they are par excellence
      political in nature. In our study, we elaborate in depth on the concept of
      organisational politics to understand the outcomes of IS implementation projects
      in hospitals. We propose a conceptual model that guides the empirical study of
      political processes in and around IS projects. Overall, our study seems to
      suggest that outcomes can be explained by the fact that stakeholders situated in
      a particular arena do tend to accept the standing power structures, even if these
      structures are built on bases that do not hold for the particular project
      environment.

PMID- 18048217
TI  - Improve processes on healthcare: current issues and future trends.
AB  - Information Technology (IT) is a critical resource for improving today's business
      competitiveness. However, many healthcare providers do not proactively manage or
      improve the efficiency and effectiveness of their services with IT. Survival in a
      competitive business environment demands continuous improvements in quality and
      service, while rigorously maintaining core values. Electronic commerce continues
      its development, gaining ground as the preferred means of business transactions.
      Embracing e-healthcare and treating IT as a strategic tool to improve patient
      safety and the quality of care enables healthcare professionals to benefit from
      technology formerly used only for management purposes. Numerous improvement
      initiatives, introduced by both the federal government and the private sector,
      seek to better the status quo in IT. This paper examines the current IT climate
      using an enhanced "Built to Last" model, and comments on future IT strategies
      within the healthcare industry.

PMID- 18048218
TI  - E-health in the new millennium: a research and practice agenda.
AB  - Advances in telecommunications, automated processes, web technologies and
      wireless computing are already forcing dramatic changes in a variety of sectors,
      ranging from business and industry to education and health. Yet, the electronic
      business space, in a broader sense, is still in a relatively early state of
      evolution, and it is only recently that policy makers have started looking at the
      potential of applying the tools and techniques of e-commerce to the tasks of
      other sectors. The use of the internet as a source of health information and
      connectivity between healthcare providers and consumers has increased interest in
      e-health. E-health offers the rich potential of supplementing traditional
      delivery of services and channels of communication in ways that extend the
      healthcare organisation's ability to meet the needs of its patients. To date,
      some e-health applications have improved the quality of healthcare, and later
      they will lead to substantial cost savings. However, e-health is not simply a
      technology but a complex technological and relational process. In this sense,
      practitioners and researchers who want to successfully exploit e-health need to
      pay attention to various pending issues that have to be addressed. The aim of
      this paper is to propose a novel taxonomy for e-health research in the new
      millennium by instantaneously presenting the current status with some major
      themes of e-health research.

PMID- 18048219
TI  - E-procurement and automatic identification: enhancing supply chain management in
      the healthcare industry.
AB  - The concepts of automated e-procurement, or electronic B2B (business-to-business)
      trade, are grounded in the strategic leveraging of both tangible/intangible
      assets for successful implementation and execution of electronic trade, resulting
      in significant financial benefits for firms. Some of the major reasons for this
      growth include significant process savings from automation, compliance, and
      purchasing advantage; and reduced costs that organisations can experience by
      conducting transactions electronically. Although these are the basic benefits
      associated with generic e-commerce strategies, a majority of these B2B
      transactions have focused on the purchase of indirect materials (especially
      office products and travel services). In fact, more than 93% of medical supplies
      on hospital shelves appear to have universal product numbers on them--at least
      while still in their boxes and there is a great potential for huge savings in e
      procurement in the healthcare field. However, other types of supply chain-related
      purchases, including maintenance, repair, and operating and replacement parts,
      and direct material purchases, are becoming more important operational management
      considerations. In addition, several other key considerations are: existing
      procurement strategy, the vendor, technology, suppliers, and total costs of
      ownership. Companies need to analyse their current procurement strategy before
      developing an e-procurement plan.

PMID- 18048220
TI  - Conception of a cost accounting model for doctors' offices.
AB  - Physicians are required, due to economical, financial, competitive, demographical
      and market-induced framework conditions, to pay increasing attention to the
      entrepreneurial administration of their offices. Because of restructuring
      policies throughout the public health system--on the grounds of increasing
      financing problems--more and better transparency of costs will be indispensable
      in all fields of medical activities in the future. The more cost-conscious public
      health insurance institutions or other public health funds will need professional
      cost accounting systems, which will provide, for minimum maintenance expense,
      standardised basis cost information as a device for decision. The conception of
      cost accounting for doctors' offices presented in this paper shows an integrated
      cost accounting approach based on activity and marginal costing philosophy. The
      conception presented provides a suitable basis for the development of standard
      software for cost accounting systems for doctors' offices.

PMID- 18048221
TI  - Innovation technology and application issues in Italian e-healthcare.
AB  - This work commences with a theoretical discussion about the relationship between
      innovation technology and application issues in Italian public and private
      healthcare. It argues that three contexts are important, namely, the "task",
      "normative" and "organisational" environments. The second part of the paper
      reports some findings from research, quantitative and qualitative approach, in
      progress. This describes the attitudes of Italian staff working in the public and
      private healthcare to the issue of innovation technology in healthcare.

PMID- 18048222
TI  - M-healthcare for patient self-management: a case for diabetics.
AB  - Disease management facilitated through information technology could mean a step
      forward towards a more effective and efficient care of patients afflicted with
      chronic illnesses. Focusing on diabetes, the paper explores the value proposition
      of wireless technology in enhancing patient self-management and quality of life.
      Diabetics' non-compliance with prescribed treatment plans mandates the adoption
      of advanced tools that can support patients through automated functions (e.g.,
      notification reminders for taking medication), decision-support (e.g., analysis
      of self-test data and feedback), and anytime/anywhere communication and
      intervention capability (e.g., emergency consultation by healthcare
      practitioner). A cost-benefit analysis for the mobile self-management of
      diabetics suggests time and financial savings for both patients and the
      healthcare providers.

PMID- 18048223
TI  - Toward a patient-centric medical information model: issues and challenges for US
      adoption.
AB  - As the USA moves, incrementally, toward evidence-based medicine, there is growing
      awareness of the importance of innovation in information management. Mandates for
      change include improved use of resources, accelerated diffusion of knowledge and
      an advanced consumer role. Key among these requirements is the need for a
      fundamentally different patient information recording system. Within the
      challenges identified in the most recent national health information technology
      initiative, we propose a model for an electronic, patient-centric medical
      information infrastructure, highlighting a transportable, scalable and integrated
      resource. We identify resources available for technology transfer, promoting
      consumers as integral parts of the collaborative medical decision-making process.

PMID- 18048224
TI  - Experiences in case mix implementation: a case study.
AB  - The health sector, being information-intensive, has tremendous potential for
      harnessing the power of information systems (IS). However, ironically, it is also
      one of the late-comers to the information-revolution. Only in the last two
      decades have UK hospitals started to become heavy investors in IS, led by
      Government initiatives to provide overarching information infrastructure and to
      make public sector organisations more accountable. One of these was the Resource
      Management Initiative, accompanied by the Case Mix IS - an organisation-wide
      system to provide clinical and management audit. Case Mix experiences in UK
      hospitals have typically been poorly documented, and those that have, paint a
      grim picture. This paper focuses on a detailed qualitative case study of a UK
      hospital that had relative success in implementation. As such, it provides a
      number of lessons learnt for other hospitals embarking on similar projects.

PMID- 18048225
TI  - Understanding physician acceptance of mobile technology: insights from two
      telephone interviews in Finland.
AB  - This paper sets out to investigate physicians' perceptions and usage regarding a
      new mobile medical information system in a pilot trial in the Finnish healthcare
      sector. Two sets of data were gathered in June and October 2003 by telephone
      interviews. The physicians interviewed had positive perceptions of the mobile
      system, and started to use it frequently in their work. They showed few negative
      experiences of using a Nokia Communicator. They favoured using mobile technology
      as a way to improve spreading medical knowledge. The main contents of the system,
      the Evidence-Based Medical Guidelines and the Pharmaca Fennica (the
      pharmacopoeia), were crucial for using the system. Some differences in
      physicians' behaviour across time were also found. Implications for system
      improvement are discussed.

PMID- 18048226
TI  - E-delivery of personalised healthcare information to intermediaries for suicide
      prevention.
AB  - A novel use of store-forward telemedicine is described in which healthcare
      information is provided via internet-based information and communication
      technologies (ICTs) to an intermediary (a third-party observer) rather than
      directly to the patient to deliver suicide prevention e-healthcare. To be
      effective, information must be tailored specifically for each type of
      intermediary to enable improved decision making in interacting with the patient.
      The healthcare system filters data and delivers personalised healthcare
      information enabled by Internet-based ICTs for a specific type of user. An
      application to mental health is presented.

PMID- 18048227
TI  - E-recruitment of patients for clinical trials.
AB  - Patient recruitment has long been a critical bottleneck in the clinical trials
      process. Current methods of media-driven recruitment efforts often fail to
      identify adequate patient numbers in a timely manner and cannot scale to meet the
      growing needs of pharmaceutical companies. The internet, on the other hand, is
      providing the opportunity to enhance patient recruitment. E-recruiting is proving
      to be a useful tool in recruiting study participants. It leverages the power of
      the internet to enrol qualified candidates for clinical trials in a more timely
      and efficient manner than traditional advertising. E-recruitment is a mass
      communication medium through which its ability to narrowcast can identify highly
      defined patient populations. The screening technology made available by health
      technology companies is a much smarter way to find qualified patients for
      clinical trials. In the end, web-based recruiting will prove to be a more
      efficient and cost-effective means of obtaining clinical study participants than
      traditional advertising methods.

PMID- 18048228
TI  - A modelling and simulation framework for compound medical applications in
      regional healthcare networks.
AB  - Regional healthcare information networks have already started to grow across
      Europe, in order to cover local healthcare provision needs, especially in
      isolated regions, where there is often no availability of central general
      hospitals. The paper discusses a modelling and simulation framework for the
      design of regional healthcare information networks running compound medical and
      QoS-sensitive applications. The proposed framework decomposes the compound
      medical applications into combinations of elementary traffic profiles, assesses
      appropriate values to the traffic parameters of the assigned models and defines
      suitable simulation scenarios. The simulation results are analysed and finally
      lead to reliable bandwidth estimations of the links of the healthcare information
      network under design. The proposed framework has been thoroughly validated
      through its application for the design of a healthcare network in the islands of
      the North Aegean Sea, running actual compound medical applications in the context
      of a national research project.

PMID- 18048229
TI  - E-healthcare: strategies to consider.
AB  - Healthcare decision makers need access to better-integrated patient information
      systems to facilitate organisational healthcare strategy, to improve patient
      satisfaction and to enhance patient outcomes. The impact of technology must be
      managed by healthcare organisations. This paper discusses strategies and explores
      operational issues needed to create a successful healthcare information system.

PMID- 18048230
TI  - A fl exible framework for managing temporal clinical trial data.
AB  - Clinical trials are processes that produce large volumes of complex data, with
      inherent temporal requirements, since the state of patients evolves during the
      trials, and the data acquisition phase itself needs to be monitored.
      Additionally, since the requirements for all clinical trials have a significant
      common portion, it is desirable to capture these common requirements in a
      generalised framework, which will be instantiated for each specific trial by
      supplementing the trial-specific requirements. In this paper, we present an
      integral approach to clinical trial management, using a temporal object-oriented
      methodology to capture and model the requirements, a temporal OODBMS for data
      storage and a generalised template application, through which trial-specific
      applications may be generated.

PMID- 18048231
TI  - The use of smart tokens to permit the secure, remote access of electronic health
      records.
AB  - A model is described whereby Electronic Health Records (EHRs) stored on a remote
      central server can be accessed from doctor's surgeries in regional Australia. The
      centrepiece of the model is a smart token on which reside unique identifiers,
      which facilitate secure, remote, transportable access by consulting physicians of
      patient clinical data, at the discretion of the patient.

PMID- 18048232
TI  - Revolution or evolution? An analysis of E-health innovation and impact using a
      hypercube model.
AB  - This study utilises a hypercube innovation model to analyse the changes in both
      healthcare informatics and medical related delivery models based on the
      innovations from Tele-healthcare, electronic healthcare (E-healthcare), to mobile
      healthcare (M-healthcare). Further, the critical impacts of these E-health
      innovations on the stakeholders: healthcare customers, hospitals, healthcare
      complementary providers and healthcare regulators are identified. Thereafter, the
      critical capabilities for adopting each innovation are discussed.

PMID- 18048233
TI  - A two-dimensional assessment of selected medical websites.
AB  - Two major dimensions are commonly used for assessing the breadth and depth of the
      information content in medical websites. The first dimension deals with quality
      characteristics consisting of authorship, attribution, confidentiality, currency,
      disclosure, legitimacy and purpose. Functional variables such as access to
      medical libraries, reference books, health organisations, information sites,
      guidelines and reviews, clinical trial sites, drug questions, locating an expert
      and alternative medicine make up the second dimension. The trend is toward the
      use of both dimensions for evaluating medical websites. This study examines the
      breadth and depth of the medical information in the websites of the top 51
      medical schools in the USA. The results of this study indicate that there are
      certain quality-standard measures that are present in all medical websites.
      However, there are also clear distinctions in quality as well as functional
      attributes that separate the higher-ranked medical schools from the lower ones.
      Medical professionals, computer system developers, and end-users of medical
      information will find the results of this study useful.

PMID- 18048234
TI  - Electronic healthcare: issues and challenges.
AB  - The shift in the nation's attention, resources and interest toward internet
      related healthcare activities, often called 'e-health', is dramatic and a most
      significant development in the healthcare environment. E-health, while exciting
      and promising, also presents new challenges, particularly in regard to acceptable
      standards, choice of technologies, overcoming traditional jurisdictional
      boundaries, up-front investment and privacy and confidentiality. This paper
      presents e-health architecture and various issues and challenges that need to be
      resolved before e-health becomes commonplace.

PMID- 18048235
TI  - Investigating enterprise application integration benefits and barriers in
      healthcare organisations: an exploratory case study.
AB  - Over the years, healthcare organisations have focused on the latest technological
      innovations to overcome their organisational problems. There was rarely a single
      approach for implementing Information Systems (IS), as healthcare organisations
      have developed their applications without a common enterprise architectural
      planning. Nowadays, dozens, if not hundreds of different types of open and
      proprietary systems exist in healthcare organisations. This growing complexity of
      healthcare IS has driven IS managers to seek applicable solutions for integrating
      their systems. As a result, different integration efforts have continuously been
      made to overcome integration problems. Recently technological developments have
      emerged in the area of integration technology such as enterprise application
      integration (EAI) and web services. This paper seeks to expand the knowledge on
      EAI, and focuses on understanding the EAI benefits and barriers in healthcare
      organisations.

PMID- 18048236
TI  - Towards evaluating health information portals: a Tasmanian E-health case study.
AB  - This paper investigates the provision of health information for rural residents
      through a web portal. Approaches to evaluate health portals are applied to a case
      study, where health information is made available through a portal accessed by
      rural Tasmanians. The portal was found to be a quality website, from an
      evaluation of its nature, success and quality.

PMID- 18048237
TI  - A decision support model of demand forecast for national immunisation vaccines.
AB  - This paper presents a demand forecast and optimal allocation model to support the
      decision making of national vaccine purchase. This research attempts to use ARIMA
      and Neural Network models respectively to forecast two individual values of 'The
      yearly total number of inoculations' and 'The annual birthrate' for the next
      year, and then choose the reasonable and better results generated from one of
      these two models to conduct a further forecast of 'The yearly total demand volume
      in doses of vaccines'. According to the experimental results, this research
      indeed may provide a feasible decision model for yearly vaccine procurement for
      Taiwan's government immunisation authority and establishes an optimal demand
      forecast model for a specific vaccine like DTP vaccine.

PMID- 18048238
TI  - Telemedicine: developing a framework to classify technology strategies.
AB  - The healthcare industry has recently been bombarded with new innovations in
      information technology (IT), one of the most promising of which is telemedicine.
      In this paper, a framework is developed, which classifies various types of
      telemedicine. Through the framework and examples, hopefully a better
      understanding of the various types is provided.

PMID- 18048239
TI  - A HL7 transformer application for vaccination data report.
AB  - In this paper, we design a data transformer to transform Comma Separated Value
      (CSV) format into Health Level Seven (HL7) messages without losing syntax and
      semantics. The algorithm of the data transformer is similar to a generic parser
      for solving scheme-level mapping problems. It can be extended to transform non
      uniform formats for exchanges among different hospital information systems. To
      show the flexibility and scalability of the algorithm, we use it for the
      transformation of reported data in the Vaccination Reporting System (VRS).
      Through the data transformer, different formats of vaccination data can be
      reported directly to the Taiwan's Center for Disease Control.

PMID- 18048240
TI  - Business pluralism of electronic prescriptions: state of development in Europe
      and the USA.
AB  - In this paper, we analyse the current state of the development of electronic
      prescriptions in Europe and the USA. These two places have different approaches
      to the healthcare sector, since in the former one national social insurance
      usually provides treatment for all of the people (most often only with friction
      from total costs), but in the latter one the healthcare sector is under free
      market forces. As our analysis shows in this paper, electronic prescriptions in
      both of the places have developed in recent years quite favourably, but this
      development has not produced consistent results, whether electronic prescriptions
      should be provided by for-profit companies or should they be under strict control
      of governmental authorities. We base this finding in two empirical observations:
      (1) in Europe saving potential from electronic prescriptions is estimated to be
      high, and contains many abstract national economy accounts and (2) leading US
      companies (providing electronic prescription services) have went been able to
      increase their revenues significantly, but still their profitability is
      questionable. We argue that the situation of electronic prescriptions is similar
      with airline or credit card industry. Both of these are vital for international
      and local economies, but the business models have developed well after the
      initial idea.

PMID- 18048241
TI  - Patient monitoring using infrastructure-oriented wireless LANs.
AB  - There is considerable interest in using wireless and mobile technologies in
      patient monitoring in diverse environments including hospitals and nursing homes.
      However, there has not been much work in determining the requirements of patient
      monitoring and satisfying these requirements using infrastructure-oriented
      wireless networks. In this paper, we derive several requirements of patient
      monitoring and show how infrastructure-oriented wireless LANs, such as versions
      of IEEE 802.11, can be used to support patient monitoring in diverse
      environments.

PMID- 18048242
TI  - Creating knowledge-driven healthcare processes with the Intelligence Continuum.
AB  - Medical science has made revolutionary changes in the past few decades.
      Contemporaneously, however, healthcare has made incremental changes at best. One
      area within healthcare that best exemplifies this is the operating room (OR). The
      growing discrepancy between the revolutionary changes in medicine and the minimal
      changes in healthcare processes leads to inefficient and ineffective healthcare
      deliver and one if not the significant contributor to the exponentially
      increasing costs plaguing healthcare globally. Significant quantities of data and
      information permeate the healthcare industry, yet the healthcare industry has not
      maximised this data resource by fully embracing key business management processes
      or techniques (such as Knowledge Management (KM), data mining, Business
      Intelligence (BI) or Business Analytics (BA)) to capitalise on realising the full
      value of this data/information resource to reengineer processes. The Intelligence
      Continuum (IC), a Mobius strip of sophisticated tools, techniques and process
      provides a systematic mechanism for healthcare organisations to facilitate
      superior clinical practice and administrative management. In this paper, the case
      example of the orthopaedic OR is used to illustrate the power of the IC in
      effecting more efficient and effective healthcare processes to ensue and thereby
      enabling healthcare to make evolutionary changes.

PMID- 18048243
TI  - Securing electronic health records with broadcast encryption schemes.
AB  - Information security is a concern in integrated electronic health record systems
      (EHRs). This paper discusses the development of a mathematical model to secure
      the access of EHRs. In this paper, we incorporate the notion of a broadcast
      encryption scheme for securing EHRs. We present a novel solution to allow a
      secure access to the EHRs whilst minimising the number of the encrypted
      ciphertexts. In a nutshell, our proposed solution enjoys shorter ciphertexts
      compared to having multiple ciphertexts encrypted for several different
      participants. Our proposed solution is applicable in practice to solve an
      existing open problem in the effort of securing EHRs.

PMID- 18048244
TI  - An examination of the financial feasibility of Electronic Medical Records (EMRs):
      a case study of tangible and intangible benefits.
AB  - Electronic Medical Records (EMRs) and associated systems have existed in various
      forms for almost ten years, yet they are still considered in their infancy
      sporting low adoption rates in US hospitals and physician practices. One of the
      key barriers to the adoption of these systems has been the concerns of healthcare
      providers that the system will not provide sufficient Return On Investment (ROI).
      This study examines the success of one medium-sized physician practice with the
      selection, implementation and ROI of an EMR. This study demonstrates that an EMR
      can provide both tangible (monetary) and intangible (clinical/quality of care)
      returns for the healthcare provider.

PMID- 18048245
TI  - Healthcare systems engineering: an interdisciplinary approach to achieving
      continuous improvement.
AB  - This paper argues that a systems approach can significantly enhance healthcare
      improvement efforts in patient safety, service quality and healthcare cost
      containment. The application of systems thinking to healthcare improvement
      encompasses three key principles: the systems perspective of healthcare
      processes, structured problem solving and the closed loop of continuous system
      improvement. These are encapsulated in a conceptual framework of continuous
      system improvement, which includes a reference architecture model and an analysis
      and design process model. Combined into a closed-loop, this framework allows
      users to understand and appropriately apply relevant functions, issues and
      analytical techniques. Practical applications of the framework are presented.

PMID- 18048246
TI  - Trial work: the way to successful information system projects in healthcare.
AB  - The lack of user knowledge about a new healthcare information system leads to
      project problems. A project's success is usually measured by end user and
      management satisfaction. The training of healthcare personnel about how to use a
      new system is not enough. Trial work is the essential and sometimes missing link
      between personnel knowledge and the successful use of an information system
      introduced in healthcare. Trial work should be carefully planned, organised and
      monitored. For best results, the trial use of the new information system has to
      be defined by management as a must for healthcare employees.

PMID- 18048247
TI  - Remote patient monitoring and information system.
AB  - This paper presents a remote healthcare patient monitoring system, called the
      Virtual Eye (VI), that utilises the World Wide Web infrastructure to monitor,
      collect, analyse and record patients' health status. The data is stored in the
      hospital database and can be accessed from anywhere through the internet. When a
      patient is in an alarming situation, the VI sends SMS messages to the mobile of
      the designated health personnel via the public GSM network. The novelty of the
      system lies in its security and its ability to use both the internet and the GSM
      network as communication media. Doctors can access the database server to compare
      the patient's current status with his/her medical history. It can be used by one
      physician to monitor a group of patients simultaneously, or by a group of
      physicians who all monitor the same patient. It allows plug-and-play of
      multivendor off-the-shelf hardware devices, thus avoiding proprietary standards.

PMID- 18048248
TI  - The specific role of ICT: different perspectives between traditional healthcare
      service and e-healthcare service.
AB  - The focus of the paper is on information technology and sustainable management in
      the healthcare service. Particularly, the challenge is: traditional healthcare
      vs. e-healthcare. A possible answer is that several dimensions are the same, but
      there are specific attributes underlying many differences enhancing new meaning
      to governance, government, knowledge and service. At this level, the managerial
      dimensions take into account six different elements: technical, relational,
      organisational, knowing, economical and communication. The e-healthcare service
      is a complex organisation, comparable to a network made of a series of crossing
      links, each one conforming to a different side of the hospital life. Its
      functional system produces modifications in the medical know-how and the managing
      profession.

PMID- 18048249
TI  - Analysis of semantic search within the domains of uncertainty: using Keyword
      Effectiveness Indexing as an evaluation tool.
AB  - Medical and health-related searches pose a special case of risk when using the
      web as an information resource. Uninsured consumers, lacking access to a trained
      provider, will often rely on information from the internet for self-diagnosis and
      treatment. In areas where treatments are uncertain or controversial, most
      consumers lack the knowledge to make an informed decision. This exploratory
      technology assessment examines the use of Keyword Effectiveness Indexing (KEI)
      analysis as a potential tool for profiling information search and keyword
      retrieval patterns. Results demonstrate that the KEI methodology can be useful in
      identifying e-health search patterns, but is limited by semantic or text-based
      web environments.

PMID- 18048250
TI  - Knowledge creation in the healthcare sector: a legitimation strategy.
AB  - There are two purposes of this study: 1. to examine the legitimacy-gaining model
      (the relationship between legitimation strategies and legitimacy) in the context
      of the hospital industry; 2. to explore the influence of the legitimacy-gaining
      model on the process through which knowledge is created within the hospital
      industry. This paper proposes a legitimacy-gaining model as the determinant of
      hospitals' knowledge-creation activities. We further suggest managerial and
      theoretical implications at the end of this paper.

PMID- 18048251
TI  - Technology assessment of resources for the emerging US e-health infrastructure: a
      proposed interoperability model.
AB  - Recent mandates in the USA related to the creation of a National Health
      Information Infrastructure (NHII) highlight the need for seamless interconnection
      of healthcare providers. As a necessary precondition, however, an interoperable
      infrastructure is needed to help clinicians get access to critical healthcare
      information upon which their clinical and/or treatment decisions can be based.
      Relatively little has been done to identify or assess commercially available
      technologies that might work together to meet the required interoperability
      requirements. In this exploratory technology assessment we examine three core
      technologies that could serve as a foundation for secure NHII interoperability:
      Source-Independent Access Control (SIAC), vault process technology and database
      independent multimedia capability.

PMID- 18048252
TI  - The influence of user interface usability on rural consumers' trust of e-health
      services.
AB  - A critical challenge facing e-health care providers today is developing a web
      presence that not only compels the consumer, but also inspires trust. This
      research is the first empirical study that systematically investigates the
      influence User Interface (UI) usability factors have on establishing trust
      between e-health consumers and e-health service providers in the context of
      exchanging personal relationship-based information. The findings of this research
      suggest that UI usability factors are essential elements in conveying the
      trustworthiness of a web-based system and do affect consumers' perception of
      trust in personal relationship-based information exchanges.

PMID- 18048253
TI  - Healthcare and technology: the doctrine of networkcentric healthcare.
AB  - Worldwide costs and the disparity between healthcare in the Western world and the
      developing countries increase exponentially. Increased involvement of ICT allows,
      in similarity to the military, a transition from platformcentric to more cohesive
      and collaborative networkcentric operations. In the information-intensive
      environment of healthcare, the networkcentric approach allows free and rapid
      sharing of information and effective knowledge building required for the
      development of coherent objectives and their rapid attainment. We suggest that
      the application of the proposed networkcentric doctrine is arguably the best
      chance of changing the way healthcare is accessed, provided and managed both
      nationally and across the globe.

PMID- 18048254
TI  - Impacts of physicians' usage of a mobile information system.
AB  - Healthcare professionals are increasingly using handheld devices in their
      practice. The applications for the handhelds are numerous and their usage
      contexts and environments vary. But the impact these mobile systems have on
      physicians' work has been somewhat unclear. This paper sets out to explain the
      impacts of a mobile information system by presenting findings from an interview
      study conducted on users of a medical information system running on a Nokia 9210
      Communicator. The impact on the work routines of the users was rather limited,
      despite the generally positive attitude towards the system. The actual usage
      patterns and the settings in which the system is used vary, and along with these
      the perceived impacts of the system on the work habits and the routines of the
      users.

PMID- 18048255
TI  - From buzzword to business strategy: the case for information and decision support
      systems in e-healthcare.
AB  - Although electronic healthcare can boast of a remarkable origin in modern-day e
      commerce in the form of Electronic Data Interchange (EDI), its mission-critical
      nature in information-based strategising is yet to be realised. Restricting the
      scope of e-healthcare management to product advertisements and website management
      reflects an unfortunate trend of underutilisation of the scope of electronic
      decision support systems in pricing and other business strategies. This paper
      aims to illustrate how this trend can be corrected by transforming e-healthcare
      into a full-fledged business strategy for strategic positioning and corporate
      profitability. This argument is illustrated with the aid of a business example
      related to transfer pricing.

PMID- 18048256
TI  - Substitute or support? Examining the role of consumer-centric e-discussion within
      domains of uncertainty.
AB  - While users of web-based information often report their reliance on such
      information for medical decision making, it has yet to be determined if this is
      universally true across all types of information or specialty domains. Some have
      argued that the web may be improperly used as 'substituted clinical judgement',
      rather than serving as a support tool for patients and their doctors. Further,
      little attention has been paid to the selective development of methodologies for
      consumer-centred discussions, or to selective grouping and analysis of debated
      'domains of uncertainty' in healthcare. Our objective in this study is to
      introduce a more refined qualitative model for discussion group or chatroom
      evaluation than has traditionally been used, and illustrate the application of
      grounded theory as an inductive framework, using assessment of e-discussion
      within an area of ongoing medical uncertainty, narcolepsy. Using this approach we
      find that while consumers often debate and discuss topics traditionally reserved
      for the doctor-patient relationship, they routinely encourage provider advice and
      dialogue within such discussions, even after experiencing unsatisfactory outcomes
      in such settings.

PMID- 18048257
TI  - Critical factors for assessing service quality of online pharmacies: a research
      framework.
AB  - There is a rapid growth of research on the online pharmacy and applications of
      the internet to pharmaceutical services. Increased data access to the general
      public has given rise to a class of sophisticated pharmaceutical consumers. With
      experienced and sophisticated consumers, rendering quality service is a key for
      online pharmacies. This paper identifies several key dimensions of service
      quality with a research framework for guiding online pharmacy systems'
      development and evaluation.

PMID- 18048258
TI  - Networkcentric healthcare: applying the tools, techniques and strategies of
      knowledge management to create superior healthcare operations.
AB  - The proliferation of Information Computer and Communication Technologies (IC2T)
      throughout the business environment has led to exponentially increasing amounts
      of data and information. Although these technologies were implemented to enhance
      and facilitate superior decision-making, the reality is information overload.
      Knowledge Management (KM) is a recent management technique designed to make sense
      of this information chaos. Critical to knowledge management is the application of
      IC2T. This paper discusses how effective and efficient healthcare operations can
      ensue through the adoption of a networkcentric healthcare perspective that is
      grounded in process-oriented knowledge generation and enabled through World
      Healthcare Information Grid (WHIG).

PMID- 18048259
TI  - The next generation of mobile medication management solutions.
AB  - In this paper, we describe the development of an internet-based system and a
      novel mobile home based device for the management of medication. We extend these
      concepts through the descriptions of an enhanced service with the use of mobile
      phone technology and home based digital TV services.

PMID- 18048260
TI  - A wireless ECG monitoring system for pervasive healthcare.
AB  - This paper presents an architectural framework of a system utilising mobile
      technologies to enable continuous, wireless, electrocardiogram (ECG) monitoring
      of cardiac patients. The proposed system has the potential to improve patients'
      quality of life by allowing them to move around freely while undergoing
      continuous heart monitoring and to reduce healthcare costs associated with
      prolonged hospitalisation, treatment and monitoring.

PMID- 18048261
TI  - Providing secure mAccess to medical information.
AB  - This paper provides the description of a pilot system, HERMES, which allows
      secure mobile access in geographically distributed medical databases. The HERMES
      system builds an environment where mobile medical personnel perform secure
      registration and acquisition of medical information. The system can be used as an
      overall medical communication system on which diverse medical applications could
      inter-operate and securely exchange data.

PMID- 18048262
TI  - Mobility in hospital work: towards a pervasive computing hospital environment.
AB  - Handheld computers are increasingly being used by hospital workers. With the
      integration of wireless networks into hospital information systems, handheld
      computers can provide the basis for a pervasive computing hospital environment;
      to develop this designers need empirical information to understand how hospital
      workers interact with information while moving around. To characterise the
      medical phenomena we report the results of a workplace study conducted in a
      hospital. We found that individuals spend about half of their time at their base
      location, where most of their interactions occur. On average, our informants
      spent 23% of their time performing information management tasks, followed by
      coordination (17.08%), clinical case assessment (15.35%) and direct patient care
      (12.6%). We discuss how our results offer insights for the design of pervasive
      computing technology, and directions for further research and development in this
      field such as transferring information between heterogeneous devices and
      integration of the physical and digital domains.

PMID- 18048263
TI  - The use of mobile devices for information sharing in a technology-supported model
      of care in A&E.
AB  - Using a case study as an example, this paper illustrates the current model of
      care in Accident and Emergency (A & E); in particular, the 'cells' in which
      data/information is stored and how explicit and accessible it is (or is not) to
      healthcare professionals. It is a model of care which may be summed up as static
      information/dynamic clinicians. This paper then describes how mobile devices may
      be used to track patients through an A&E department. From there, a model of care
      is proposed that has at its core the notion of dynamic information/static
      clinicians which takes into account the potential and likelihood of such mobile
      technology being used to support healthcare professionals in the future. It is
      argued, however, that such 'disruptive technologies' are merely tools at our
      disposal and that it is human activity which must be foremost when considering
      how we might work differently ('better') in treating and/or dealing with
      patients.

PMID- 18048264
TI  - An intelligent pre-hospital patient care system.
AB  - iRevive is a sensor-supported, pre-hospital patient care system for the capture
      and transmittal of electronic patient data from the field to hospitals. It is
      being developed by 10Blade and Boston MedFlight. iRevive takes advantage of
      emerging technologies to offer a robust, flexible, and extensible IT
      infrastructure for patient data collection.

PMID- 18048265
TI  - Human and organisational aspects of remote patient monitoring in residential care
      homes.
AB  - Demographic changes in the population, with a growing proportion of elderly
      people, make the efficient and effective provision of healthcare for this age
      group an increasingly important issue. We examine the organisational and human
      aspects of introducing a Remote Patient Monitoring (RPM) system that uses
      wireless and broadband networks into three residential care homes in the UK.
      Stakeholders were identified, and semi-structured one-to-one interviews were
      carried out in order to identify issues deemed most important to each group. The
      work is novel, as it requires examination of the issues of communication between
      healthcare workers in several primary and secondary care organisations. The key
      finding was the need to identify the changes in working practice and
      interpersonal communication. A key factor in particular was the change in
      relationships: staff in the remote centre needing to learn to seek support when
      reporting and requesting assistance for a problem; and for the staff at the
      health centres to respond appropriately.

PMID- 18048266
TI  - A multimedia PDA/PC speech and language therapy tool for patients with aphasia.
AB  - Aphasia is a speech disorder usually caused by stroke or head injury and may
      involve a variety of communication difficulties. As 30% of stroke sufferers have
      a persisting speech and language disorder and therapy resources are low, there is
      clear scope for the development of technology to support patients between therapy
      sessions. This paper reports on an empirical study which evaluated SoundHelper, a
      multimedia application to demonstrate how to pronounce target speech sounds. Two
      prototypes, involving either video or animation, were developed and evaluated
      with 20 Speech and Language Therapists. Participants responded positively to
      both, with the video being preferred because of the perceived extra information
      provided. The potential for the use on portable devices, since internet access is
      limited in hospitals, is explored in the light of opinions of Augmented and
      Alternative Communication (AAC) device users in the UK nd Europe who have
      expressed a strong desire for more use of internet services.

PMID- 18048267
TI  - Framework and prototype for a secure XML-based electronic health records system.
AB  - Security of personal medical information has always been a challenge for the
      advancement of Electronic Health Records (EHRs) initiatives. eXtensible Markup
      Language (XML), is rapidly becoming the key standard for data representation and
      transportation. The widespread use of XML and the prospect of its use in the
      Electronic Health (e-health) domain highlights the need for flexible access
      control models for XML data and documents. This paper presents a declarative
      access control model for XML data repositories that utilises an expressive XML
      role control model. The operational semantics of this model are illustrated by
      Xplorer, a user interface generation engine which supports search-browse-navigate
      activities on XML repositories.

PMID- 18048268
TI  - Improving patient safety with RFID and mobile technology.
AB  - Medical errors have become a leading cause of death, killing more people each
      year than AIDS or aeroplane crashes. These medical errors can be classified into
      five categories: poor decision making, poor communication, inadequate patient
      monitoring, patient misidentification, inability to respond rapidly and poor
      patient tracking. Employing innovative information technologies in correcting
      these deficiencies and meeting the Joint Commission on Accreditation of
      Healthcare Organistion (JCAHO) patient safety goals is the current trend in
      enhancing patient safety.

PMID- 18048269
TI  - Obstacles to the adoption of radio frequency identification technology in the
      emergency rooms of hospitals.
AB  - The Emergency Room (ER) receives patients in critical conditions. The operation
      of many emergency service chains is hampered because the required medical
      equipment is not always conveniently available and patient vital signs are
      manually monitored, but not automatically tracked on a real-time basis. This has
      resulted in medical errors, increased stress levels of medical teams, and poor
      utilisation of staff and equipment. Our research investigates factors that
      contribute to the adoption of Radio Frequency Identification (RFID) technologies
      by the medical team in ERs. We propose a theoretical framework to address this
      issue based upon the Unified Theory of Acceptance and Use of Technology (UTAUT)
      theory.

PMID- 18048270
TI  - High-end clinical domain information systems for effective healthcare delivery.
AB  - The Electronic Health Record (EHR) provides doctors with a quick, reliable,
      secure, real-time and user-friendly source of all relevant patient data. The
      latest information system technologies, such as Clinical Data Warehouses (CDW),
      Clinical Decision-Support (CDS) systems and data-mining techniques (Online
      Analytical Processing (OLAP) and Online Transactional Processing (OLTP)), are
      used to maintain and utilise patient data intelligently, based on the users'
      requirements. Moreover, clinical trial reports for new drug approvals are now
      being submitted electronically for faster and easier processing. Also,
      information systems are used in educating patients about the latest developments
      in medical science through the internet and specially configured kiosks in
      hospitals and clinics.

PMID- 18048271
TI  - Influential factors on physicians' behaviour towards the medical web messaging
      board: a qualitative exploration.
AB  - In the past, researches showed that patients expected to communicate with
      physicians through the internet, but physicians presented conservative attitudes.
      In this research, researchers interview 20 physicians who have communicated with
      patients through the medical web messaging board. The results reveal some factors
      that influence physicians' behaviour towards adopting it: in the personal aspect,
      physicians' slow typing skills in Chinese and patients' insufficient medical
      knowledge are factors. In the medical aspect, diseases changing with time, and
      the complexity of the medical knowledge are factors. In technological aspects,
      lack of instant response device and physical examination are factors. Thus,
      physicians avoid diagnosing through the online board. Physicians use the online
      board to educate and comfort patients.

PMID- 18048272
TI  - Hospital information management system: an evolutionary knowledge management
      perspective.
AB  - The evolving paradigm shift resulting from IT, social and technological changes
      has created a need for developing an innovative knowledge-based healthcare
      system, which can effectively meet global healthcare system demands and also
      cater to future trends. The Hospital Information Management System (HIMS) is
      developed with this sole aim in mind, which helps in processing and management of
      hospital information not only inside the boundary, but also beyond the hospital
      boundary, e.g., telemedicine or e-healthcare. The purpose of this paper is to
      present such kind of functional HIMS, which can efficiently satisfy the current
      and future system requirements by using Knowledge Management (KM) and data
      management systems. The HIMS is developed in a KM context, wherein users can
      share and use the knowledge more effectively. The proposed system is fully
      compatible with future technical, social, managerial and economical requirements.

PMID- 18048273
TI  - Critical success factors for achieving superior m-health success.
AB  - Recent healthcare trends clearly show significant investment by healthcare
      institutions into various types of wired and wireless technologies to facilitate
      and support superior healthcare delivery. This trend has been spurred by the
      shift in the concept and growing importance of the role of health information and
      the influence of fields such as bio-informatics, biomedical and genetic
      engineering. The demand is currently for integrated healthcare information
      systems; however for such initiatives to be successful it is necessary to adopt a
      macro model and appropriate methodology with respect to wireless initiatives. The
      key contribution of this paper is the presentation of one such integrative model
      for mobile health (m-health) known as the Wi-INET Business Model, along with a
      detailed Adaptive Mapping to Realisation (AMR) methodology. The AMR methodology
      details how the Wi-INET Business Model can be implemented. Further validation on
      the concepts detailed in the Wi-INET Business Model and the AMR methodology is
      offered via a short vignette on a toolkit based on a leading UK-based healthcare
      information technology solution.

PMID- 18048274
TI  - Securing electronic health records with novel mobile encryption schemes.
AB  - Mobile devices have penetrated the healthcare sector due to their increased
      functionality, low cost, high reliability and easy-to-use nature. However, in
      healthcare applications the privacy and security of the transmitted information
      must be preserved. Therefore applications require a concrete security framework
      based on long-term security keys, such as the security key that can be found in a
      mobile Subscriber Identity Module (SIM). The wireless nature of communication
      links in mobile networks presents a major challenge in this respect. This paper
      presents a novel protocol that will send the information securely while including
      the access privileges to the authorized recipient.

PMID- 18048275
TI  - The Internet and healthcare in Taiwan: value-added applications on the medical
      network in the National Health Insurance smart card system.
AB  - The introduction of smart card technology has ushered in a new era of electronic
      medical information systems. Taiwan's Bureau of National Health Insurance (BNHI)
      implemented the National Health Insurance (NHI) smart card project in 2004. The
      purpose of the project was to replace all paper cards with one smart card. The
      NHI medical network now provides three kinds of services. In this paper, we
      illustrate the status of the NHI smart card system in Taiwan and propose three
      kinds of value-added applications for the medical network, which are electronic
      exchange of medical information, retrieval of personal medical records and
      medical e-learning for future development of health information systems.

PMID- 18048276
TI  - An Eclipse-based development approach to health information technology.
AB  - The rapid proliferation of applications--electronic health record and clinical
      decision support systems among them--cannot keep up with the growing needs of
      healthcare delivery organisations. The absence of uniform standards and
      interoperability has hindered the successful deployment and acceptance of these
      applications. Eclipse and other open source applications have the potential to
      fill some of these gaps. The benefits include acceptance of open standards,
      enabling interoperability and scalability, prevention of vendor lock-in and lower
      costs. In this paper, we describe an Eclipse-based open source electronic health
      record application, a prototype. We contrast the Eclipse approach to other
      development approaches. Implementation is feasible and provides customization,
      although there are challenges to overcome. We envision organisations adopting
      open source development tools as alternatives to vendor-driven, proprietary
      systems.

PMID- 18048277
TI  - Evaluation of investment for enterprise application integration technology in
      healthcare organisations: a cost-benefit approach.
AB  - Recent developments in the field of Information Technology (IT), such as
      integration technologies have promised to bring improvements in the quality of
      services; however, costs of these technologies are relatively high. Consequently,
      investment justification for these technologies is one of the many challenges
      that are faced by managers in healthcare organisations. IT investments in
      healthcare organisations are usually justified using traditional investment
      appraisal techniques such as Return on Investment (ROI) analysis, internal rate
      of return, net present value and payback approach. The techniques are
      specifically used to measure the financial impact of the investment; therefore,
      the techniques are limited to accommodate human and organisational benefits
      associated with the adoption of integration technologies. In exploring this
      phenomenon, the paper focuses on benefits and costs of Enterprise Application
      Integration (EAI) adoption in healthcare organisations. This may be useful for
      the managers in preparing investment budget proposals.

PMID- 18048278
TI  - Principles and effects of electronic communication systems between healthcare
      providers and managed-care organisations.
AB  - The present paper studies the issue of electronic communication among healthcare
      providers, patients and Managed-Care Organisations (MCOs) and how this
      communication could be exploited in order to increase the quality of health
      services. Specifically, we review the existing electronic communication systems
      in health and how they are used by the stakeholders and the medical staff. After
      reviewing the barriers to using online communication in clinical practice, we
      emphasise the challenges and the advantages of embodying such systems in daily
      healthcare services.

PMID- 18048279
TI  - An intelligent agent approach to improving the coordination efficiency in the
      donor kidney distribution process.
AB  - Kidney transplantation is an effective treatment for an end-stage renal disease.
      Donor kidneys need to be matched with appropriate patients, distributed and
      transplanted very quickly (less than 40 hr) in order to achieve optimal medical
      results. In this paper we analyse the bottlenecks in the current donor kidney
      distribution process and investigate how agent technology can be applied to
      improve this process. We propose a distributed multi-agent system operating in a
      mobile communication environment to assist transplant coordinators in
      coordinating with multiparties in this time-critical distribution process. A
      prototype system has been developed to demonstrate the feasibility of such a
      system.

PMID- 18048280
TI  - Harmless nectar source or deadly trap: Nepenthes pitchers are activated by rain,
      condensation and nectar.
AB  - The leaves of Nepenthes pitcher plants are specialized pitfall traps which
      capture and digest arthropod prey. In many species, insects become trapped by
      'aquaplaning' on the wet pitcher rim (peristome). Here we investigate the
      ecological implications of this capture mechanism in Nepenthes rafflesiana var.
      typica. We combine meteorological data and continuous field measurements of
      peristome wetness using electrical conductance with experimental assessments of
      the pitchers' capture efficiency. Our results demonstrate that pitchers can be
      highly effective traps with capture rates as high as 80% but completely
      ineffective at other times. These dramatic changes are due to the wetting
      condition of the peristome. Variation of peristome wetness and capture efficiency
      was perfectly synchronous, and caused by rain, condensation and nectar secreted
      from peristome nectaries. The presence of nectar on the peristome increased
      surface wetness mainly indirectly by its hygroscopic properties. Experiments
      confirmed that pitchers with removed peristome nectaries remained generally drier
      and captured prey less efficiently than untreated controls. This role of nectar
      in prey capture represents a novel function of plant nectar. We propose that the
      intermittent and unpredictable activation of Nepenthes pitcher traps facilitates
      ant recruitment and constitutes a strategy to maximize prey capture.

PMID- 18048281
TI  - Crowding, sex ratio and horn evolution in a South African beetle community.
AB  - Sexually selected ornaments and weapons are exceptionally variable, even between
      closely related species. It has long been recognized that some of this diversity
      can be explained by differences in mating systems between species, but there
      remains substantial variation between species with similar mating systems. We
      investigated the roles of sex ratio (measured as operational sex ratio, OSR) and
      population density (measured as mean male crowding, a measure indicating the
      average number of conspecific males that an individual male animal will
      encounter) in determining horn presence in a community of South African dung
      beetles. Analysis of data from 14 species using a generalized least-squares model
      incorporating phylogenetic influences found that both OSR and mean crowding were
      significant predictors of horn presence, with hornless species tending to show
      female-biased sex ratios and high levels of crowding. The influence of mean
      crowding on horn diversity between species probably reflects the difficulty of
      guarding and monopolizing females when many competitors are present, meaning that
      males who adopt 'scramble' tactics tend to be favoured.

PMID- 18048282
TI  - Cheating honeybee workers produce royal offspring.
AB  - The Cape bee (Apis mellifera capensis) is unique among honeybees in that workers
      can lay eggs that instead of developing into males develop into females via
      thelytokous parthenogenesis. We show that this ability allows workers to compete
      directly with the queen over the production of new queens. Genetic analyses using
      microsatellites revealed that 23 out of 39 new queens produced by seven colonies
      were offspring of workers and not the resident queen. Of these, eight were laid
      by resident workers, but the majority were offspring of parasitic workers from
      other colonies. The parasites were derived from several clonal lineages that
      entered the colonies and successfully targeted queen cells for parasitism. Hence,
      these parasitic workers had the potential to become genetically reincarnated as
      queens. Of the daughter queens laid by the resident queen, three were produced
      asexually, suggesting that queens can 'choose' to produce daughter queens
      clonally and thus have the potential for genetic immortality.

PMID- 18048283
TI  - Pattern and timing of diversification in Yucca (Agavaceae): specialized
      pollination does not escalate rates of diversification.
AB  - The yucca-yucca moth interaction is one of the most well-known and remarkable
      obligate pollination mutualisms, and is an important study system for
      understanding coevolution. Previous research suggests that specialist pollinators
      can promote rapid diversification in plants, and theoretical work has predicted
      that obligate pollination mutualism promotes cospeciation between plants and
      their pollinators, resulting in contemporaneous, parallel diversification.
      However, a lack of information about the age of Yucca has impeded efforts to test
      these hypotheses. We used analyses of 4322 AFLP markers and cpDNA sequence data
      representing six non-protein-coding regions (trnT-trnL, trnL, trnL intron, trnL
      trnF, rps16 and clpP intron 2) from all 34 species to recover a consensus
      organismal phylogeny, and used penalized likelihood to estimate divergence times
      and speciation rates in Yucca. The results indicate that the pollination
      mutualism did not accelerate diversification, as Yucca diversity (34 species) is
      not significantly greater than that of its non-moth-pollinated sister group,
      Agave sensu latissimus (240 species). The new phylogenetic estimates also
      corroborate the suggestion that the plant-moth pollination mutualism has at least
      two origins within the Agavaceae. Finally, age estimates show significant discord
      between the age of Yucca (ca 6-10Myr) and the current best estimates for the age
      of their pollinators (32-40Myr).

PMID- 18048284
TI  - Experimental alteration of litter sex ratios in a mammal.
AB  - Adaptive theory predicts that mothers would be advantaged by adjusting the sex
      ratio of their offspring in relation to their offspring's future reproductive
      success. Studies investigating sex ratio variation in mammals, including humans,
      have obtained notoriously inconsistent results, except when maternal condition is
      measured around conception. Several mechanisms for sex ratio adjustment have been
      proposed. Here, we test the hypothesis that glucose concentrations around
      conception influence sex ratios. The change in glucose levels resulted in a
      change in sex ratios, with more daughters being born to females with
      experimentally lowered glucose, and with the change in glucose levels being more
      predictive than the glucose levels per se. We provide evidence for a mechanism,
      which, in tandem with other mechanisms, could explain observed sex ratio
      variation in mammals.

PMID- 18048285
TI  - Filling the gap between identified neuroblasts and neurons in crustaceans adds
      new support for Tetraconata.
AB  - The complex spatio-temporal patterns of development and anatomy of nervous
      systems play a key role in our understanding of arthropod evolution. However, the
      degree of resolution of neural processes is not always detailed enough to claim
      homology between arthropod groups. One example is neural precursors and their
      progeny in crustaceans and insects. Pioneer neurons of crustaceans and insects
      show some similarities that indicate homology. In contrast, the differentiation
      of insect and crustacean neuroblasts (NBs) shows profound differences and their
      homology is controversial. For Drosophila and grasshoppers, the complete lineage
      of several NBs up to formation of pioneer neurons is known. Apart from data on
      median NBs no comparable results exist for Crustacea. Accordingly, it is not
      clear where the crustacean pioneer neurons come from and whether there are NBs
      lateral to the midline homologous to those of insects. To fill this gap,
      individual NBs in the ventral neuroectoderm of the crustacean Orchestia cavimana
      were labelled in vivo with a fluorescent dye. A partial neuroblast map was
      established and for the first time lineages from individual NBs to identified
      pioneer neurons were established in a crustacean. Our data strongly suggest
      homology of NBs and their lineages, providing further evidence for a close insect
      crustacean relationship.

PMID- 18048286
TI  - Climate change and the effects of temperature extremes on Australian flying
      foxes.
AB  - Little is known about the effects of temperature extremes on natural systems.
      This is of increasing concern now that climate models predict dramatic increases
      in the intensity, duration and frequency of such extremes. Here we examine the
      effects of temperature extremes on behaviour and demography of vulnerable wild
      flying-foxes (Pteropus spp.). On 12 January 2002 in New South Wales, Australia,
      temperatures exceeding 42 degrees C killed over 3500 individuals in nine mixed
      species colonies. In one colony, we recorded a predictable sequence of
      thermoregulatory behaviours (wing-fanning, shade-seeking, panting and saliva
      spreading, respectively) and witnessed how 5-6% of bats died from hyperthermia.
      Mortality was greater among the tropical black flying-fox, Pteropus alecto (10
      13%) than the temperate grey-headed flying-fox, Pteropus poliocephalus (less than
      1%), and young and adult females were more affected than adult males (young, 23
      49%; females, 10-15%; males, less than 3%). Since 1994, over 30000 flying-foxes
      (including at least 24500 P. poliocephalus) were killed during 19 similar events.
      Although P. alecto was relatively less affected, it is currently expanding its
      range into the more variable temperature envelope of P. poliocephalus, which
      increases the likelihood of die-offs occurring in this species. Temperature
      extremes are important additional threats to Australian flying-foxes and the
      ecosystem services they provide, and we recommend close monitoring of colonies
      where temperatures exceeding 42.0 degrees C are predicted. The effects of
      temperature extremes on flying-foxes highlight the complex implications of
      climate change for behaviour, demography and species survival.

PMID- 18048287
TI  - Persistence of the emerging pathogen Batrachochytrium dendrobatidis outside the
      amphibian host greatly increases the probability of host extinction.
AB  - Pathogens do not normally drive their hosts to extinction; however,
      Batrachochytrium dendrobatidis, which causes amphibian chytridiomycosis, has been
      able to do so. Theory predicts that extinction can be caused by long-lived or
      saprobic free-living stages. The hypothesis that such a stage occurs in B.
      dendrobatidis is supported by the recent discovery of an apparently encysted form
      of the pathogen. To investigate the effect of a free-living stage of B.
      dendrobatidis on host population dynamics, a mathematical model was developed to
      describe the introduction of chytridiomycosis into a breeding population of Bufo
      bufo, parametrized from laboratory infection and transmission experiments. The
      model predicted that the longer that B. dendrobatidis was able to persist in
      water, either due to an increased zoospore lifespan or saprobic reproduction, the
      more likely it was that it could cause local B. bufo extinction (defined as
      decrease below a threshold level). Establishment of endemic B. dendrobatidis
      infection in B. bufo, with severe host population depression, was also possible,
      in agreement with field observations. Although this model is able to predict
      clear trends, more precise predictions will only be possible when the life
      history of B. dendrobatidis, including free-living stages of the life cycle, is
      better understood.

PMID- 18048288
TI  - Individual variation and the endocrine regulation of behaviour and physiology in
      birds: a cellular/molecular perspective.
AB  - Investigations of the cellular and molecular mechanisms of physiology and
      behaviour have generally avoided attempts to explain individual differences. The
      goal has rather been to discover general processes. However, understanding the
      causes of individual variation in many phenomena of interest to avian eco
      physiologists will require a consideration of such mechanisms. For example, in
      birds, changes in plasma concentrations of steroid hormones are important in the
      activation of social behaviours related to reproduction and aggression. Attempts
      to explain individual variation in these behaviours as a function of variation in
      plasma hormone concentrations have generally failed. Cellular variables related
      to the effectiveness of steroid hormone have been useful in some cases. Steroid
      hormone target sensitivity can be affected by variables such as metabolizing
      enzyme activity, hormone receptor expression as well as receptor cofactor
      expression. At present, no general theory has emerged that might provide a clear
      guidance when trying to explain individual variability in birds or in any other
      group of vertebrates. One strategy is to learn from studies of large units of
      intraspecific variation such as population or sex differences to provide ideas
      about variables that might be important in explaining individual variation. This
      approach along with the use of newly developed molecular genetic tools represents
      a promising avenue for avian eco-physiologists to pursue.

PMID- 18048289
TI  - Variation in maternal effects and embryonic development rates among passerine
      species.
AB  - Embryonic development rates are reflected by the length of incubation period in
      birds, and these vary substantially among species within and among geographical
      regions. The incubation periods are consistently shorter in North America
      (Arizona study site) than in tropical (Venezuela) and subtropical (Argentina)
      South America based on the study of 83 passerine species in 17 clades. Parents,
      mothers in particular, may influence incubation periods and resulting offspring
      quality through proximate pathways, while variation in maternal strategies among
      species can result from selection by adult and offspring mortality. Parents of
      long-lived species, as is common in the tropics and subtropics, may be under
      selection to minimize costs to themselves during incubation. Indeed, time spent
      incubating is often lower in the tropical and subtropical species than the
      related north temperate species, causing cooler average egg temperatures in the
      southern regions. Decreased egg temperatures result in longer incubation periods
      and reflect a cost imposed on offspring by parents because energy cost to the
      embryo and risk of offspring predation are both increased. Mothers may adjust egg
      size and constituents as a means to partially offset such costs. For example,
      reduced androgen concentrations in egg yolks may slow development rates, but may
      enhance offspring quality through physiological trade-offs that may be
      particularly beneficial in longer-lived species, as in the tropics and
      subtropics. We provide initial data to show that yolks of tropical birds contain
      substantially lower concentrations of growth-promoting androgens than north
      temperate relatives. Thus, maternal (and parental) effects on embryonic
      development rates may include contrasting and complementary proximate influences
      on offspring quality and deserve further field study among species.

PMID- 18048290
TI  - Neuroendocrine control of life histories: what do we need to know to understand
      the evolution of phenotypic plasticity?
AB  - Almost all life histories are phenotypically plastic: that is, life-history
      traits such as timing of breeding, family size or the investment in individual
      offspring vary with some aspect of the environment, such as temperature or food
      availability. One approach to understanding this phenotypic plasticity from an
      evolutionary point of view is to extend the optimality approach to the range of
      environments experienced by the organism. This approach attempts to understand
      the value of particular traits in terms of the selection pressures that act on
      them either directly or owing to trade-offs due to resource allocation and other
      factors such as predation risk. Because these selection pressures will between
      environments, the predicted optimal phenotype will too. The relationship
      expressing the optimal phenotype for different environments is the optimal
      reaction norm and describes the optimal phenotypic plasticity. However, this view
      of phenotypic plasticity ignores the fact that the reaction norm must be
      underlain by some sort of control system: cues about the environment must be
      collected by sense organs, integrated into a decision about the appropriate life
      history, and a message sent to the relevant organs to implement that decision. In
      multicellular animals, this control mechanism is the neuroendocrine system. The
      central question that this paper addresses is whether the control system affects
      the reaction norm that evolves. This might happen in two different ways: first,
      the control system will create constraints on the evolution of reaction norms if
      it cannot be configured to produce the optimal reaction norm and second, the
      control system will create additional selection pressures on reaction norms if
      the neuroendocrine system is costly. If either of these happens, a full
      understanding of the way in which selection shapes reaction norms must include
      details of the neuroendocrine control system. This paper presents the conceptual
      framework needed to explain what is meant by a constraint or cost being created
      by the neuroendocrine system and discusses the extent to which this occurs and
      some possible examples. The purpose of doing this is to encourage
      endocrinologists to take a fresh look at neuroendocrine mechanisms and help
      identify the properties of the system and situations in which these generate
      constraints and costs that impinge on the evolution of phenotypic plasticity.

PMID- 18048291
TI  - Hormone-mediated maternal effects in birds: mechanisms matter but what do we know
      of them?
AB  - Over the past decade, birds have proven to be excellent models to study hormone
      mediated maternal effects in an evolutionary framework. Almost all these studies
      focus on the function of maternal steroid hormones for offspring development, but
      lack of knowledge about the underlying mechanisms hampers further progress. We
      discuss several hypotheses concerning these mechanisms, point out their relevance
      for ecological and evolutionary interpretations, and review the relevant data. We
      first examine whether maternal hormones can accumulate in the egg independently
      of changes in hormone concentrations in the maternal circulation. This is
      important for Darwinian selection and female physiological trade-offs, and
      possible mechanisms for hormone accumulation in the egg, which may differ among
      hormones, are reviewed. Although independent regulation of plasma and yolk
      concentrations of hormones is conceivable, the data are as yet inconclusive for
      ovarian hormones. Next, we discuss embryonic utilization of maternal steroids,
      since enzyme and receptor systems in the embryo may have coevolved with maternal
      effect mechanisms in the mother. We consider dose-response relationships and
      action pathways of androgens and argue that these considerations may help to
      explain the apparent lack of interference of maternal steroids with sexual
      differentiation. Finally, we discuss mechanisms underlying the pleiotropic
      actions of maternal steroids, since linked effects may influence the coevolution
      of parent and offspring traits, owing to their role in the mediation of
      physiological trade-offs. Possible mechanisms here are interactions with other
      hormonal systems in the embryo. We urge endocrinologists to embark on suggested
      mechanistic studies and behavioural ecologists to adjust their interpretations to
      accommodate the current knowledge of mechanisms.

PMID- 18048292
TI  - Review. Meiotic drive and sex determination: molecular and cytological mechanisms
      of sex ratio adjustment in birds.
AB  - Differences in relative fitness of male and female offspring across ecological
      and social environments should favour the evolution of sex-determining mechanisms
      that enable adjustment of brood sex ratio to the context of breeding. Despite the
      expectation that genetic sex determination should not produce consistent bias in
      primary sex ratios, extensive and adaptive modifications of offspring sex ratio
      in relation to social and physiological conditions during reproduction are often
      documented. Such discordance emphasizes the need for empirical investigation of
      the proximate mechanisms for modifying primary sex ratios, and suggests
      epigenetic effects on sex-determining mechanisms as the most likely candidates.
      Birds, in particular, are thought to have an unusually direct opportunity to
      modify offspring sex ratio because avian females are heterogametic and because
      the sex-determining division in avian meiosis occurs prior to ovulation and
      fertilization. However, despite evidence of strong epigenetic effects on sex
      determination in pre-ovulatory avian oocytes, the mechanisms behind such effects
      remain elusive. Our review of molecular and cytological mechanisms of avian
      meiosis uncovers a multitude of potential targets for selection on biased
      segregation of sex chromosomes, which may reflect the diversity of mechanisms and
      levels on which such selection operates in birds. Our findings indicate that
      pronounced differences between sex chromosomes in size, shape, size of protein
      bodies, alignment at the meiotic plate, microtubule attachment and epigenetic
      markings should commonly produce biased segregation of sex chromosomes as the
      default state, with secondary evolution of compensatory mechanisms necessary to
      maintain unbiased meiosis. We suggest that it is the epigenetic effects that
      modify such compensatory mechanisms that enable context-dependent and precise
      adjustment of primary sex ratio in birds. Furthermore, we highlight the features
      of avian meiosis that can be influenced by maternal hormones in response to
      environmental stimuli and may account for the precise and adaptive patterns of
      offspring sex ratio adjustment observed in some species.

PMID- 18048293
TI  - Review. Do hormonal control systems produce evolutionary inertia?
AB  - Hormonal control systems are complex in design and well integrated. Concern has
      been raised that these systems might act as evolutionary constraints when animals
      are subject to anthropogenic environmental change. Three systems are examined in
      vertebrates, especially birds, that are important for assessing this possibility:
      (i) the hypothalamic-pituitary-gonadal (HPG) axis, (ii) the activational effects
      of sex steroids on mating effort behaviour, and (iii) sexual differentiation.
      Consideration of how these systems actually work that takes adequate account of
      the brain's role and mechanisms suggests that the first two are unlikely to be
      impediments to evolution. The neural and molecular networks that regulate the HPG
      provide both phenotypic and evolutionary flexibility, and rapid evolutionary
      responses to selection have been documented in several species. The
      neuroendocrine and molecular cascades for behaviour provide many avenues for
      evolutionary change without requiring a change in peripheral hormone levels.
      Sexual differentiation has some potential to be a source of evolutionary inertia
      in birds and could contribute to the lack of diversity in certain reproductive
      (including life history) traits. It is unclear, however, whether that lack of
      diversity would impede adaptation to rapid environmental change given the role of
      behavioural flexibility in avian reproduction.

PMID- 18048294
TI  - Control of the annual cycle in birds: endocrine constraints and plasticity in
      response to ecological variability.
AB  - This paper reviews information from ecological and physiological studies to
      assess how extrinsic factors can modulate intrinsic physiological processes. The
      annual cycle of birds is made up of a sequence of life-history stages: breeding,
      moult and migration. Each stage has evolved to occur at the optimum time and to
      last for the whole duration of time available. Some species have predictable
      breeding seasons, others are more flexible and some breed opportunistically in
      response to unpredictable food availability. Photoperiod is the principal
      environmental cue used to time each stage, allowing birds to adapt their
      physiology in advance of predictable environmental changes. Physiological
      (neuroendocrine and endocrine) plasticity allows non-photoperiodic cues to
      modulate timing to enable individuals to cope with, and benefit from, short-term
      environmental variability. Although the timing and duration of the period of full
      gonadal maturation is principally controlled by photoperiod, non-photoperiodic
      cues, such as temperature, rainfall or food availability, could potentially
      modulate the exact time of breeding either by fine-tuning the time of egg-laying
      within the period of full gonadal maturity or, more fundamentally, by modulating
      gonadal maturation and/or regression. The timing of gonadal regression affects
      the time of the start of moult, which in turn may affect the duration of the
      moult. There are many areas of uncertainty. Future integrated studies are
      required to assess the scope for flexibility in life-history strategies as this
      will have a critical bearing on whether birds can adapt sufficiently rapidly to
      anthropogenic environmental changes, in particular climate change.

PMID- 18048295
TI  - Individual variation in endocrine systems: moving beyond the 'tyranny of the
      Golden Mean'.
AB  - Twenty years ago, Albert Bennett published a paper in the influential book New
      directions in ecological physiology arguing that individual variation was an
      'underutilized resource'. In this paper, I review our state of knowledge of the
      magnitude, mechanisms and functional significance of phenotypic variation,
      plasticity and flexibility in endocrine systems, and argue for a renewed focus on
      inter-individual variability. This will provide challenges to conventional wisdom
      in endocrinology itself, e.g. re-evaluation of relatively simple, but unresolved
      questions such as structure-function relationships among hormones, binding
      globulins and receptors, and the functional significance of absolute versus
      relative hormone titres. However, there are also abundant opportunities for
      endocrinologists to contribute solid mechanistic understanding to key questions
      in evolutionary biology, e.g. how endocrine regulation is involved in evolution
      of complex suites of traits, or how hormone pleiotropy regulates trade-offs among
      life-history traits. This will require endocrinologists to embrace the raw
      material of adaptation (heritable, individual variation and phenotypic
      plasticity) and to take advantage of conceptual approaches widely used in
      evolutionary biology (selection studies, reaction norms, concepts of evolutionary
      design) as well as a more explicit focus on the endocrine basis of life-history
      traits that are of primary interest to evolutionary biologists (cf. behavioural
      endocrinology).

PMID- 18048296
TI  - Hormone-mediated suites as adaptations and evolutionary constraints.
AB  - Hormones mediate the expression of suites of correlated traits and hence may act
      both to facilitate and constrain adaptive evolution. Selection on one trait
      within a hormone-mediated suite may, for example, lead to a change in the
      strength of the hormone signal, causing either beneficial or detrimental changes
      in correlated traits. Theory and empirical methods for studying correlated trait
      evolution have been developed by the field of evolutionary quantitative genetics,
      and here we suggest that their application to the study of hormone-mediated
      suites may prove fruitful. We present hypotheses for how selection shapes the
      evolution of hormone-mediated suites and argue that correlational selection,
      which arises when traits interact in their effects on fitness, may act to alter
      or conserve the composition of hormone-mediated suites. Next, we advocate using
      quantitative genetic methods to assess natural covariation among hormone-mediated
      traits and to measure the strength of natural selection acting on them. Finally,
      we present illustrative examples from our own work on the evolution of
      testosterone-mediated suites in male and female dark-eyed juncos. We conclude
      that future work on hormone-mediated suites, if motivated by quantitative genetic
      theory, may provide important insights into their dual roles as adaptations and
      evolutionary constraints.

PMID- 18048298
TI  - Spatially explicit fire-climate history of the boreal forest-tundra (Eastern
      Canada) over the last 2000 years.
AB  - Across the boreal forest, fire is the main disturbance factor and driver of
      ecosystem changes. In this study, we reconstructed a long-term, spatially
      explicit fire history of a forest-tundra region in northeastern Canada. We
      hypothesized that current occupation of similar topographic and edaphic sites by
      tundra and forest was the consequence of cumulative regression with time of
      forest cover due to compounding fire and climate disturbances. All fires were
      mapped and dated per 100 year intervals over the last 2,000 years using several
      fire dating techniques. Past fire occurrences and post-fire regeneration at the
      northern forest limit indicate 70% reduction of forest cover since 1800 yr BP and
      nearly complete cessation of forest regeneration since 900 yr BP. Regression of
      forest cover was particularly important between 1500s-1700s and possibly since
      900 yr BP. Although fire frequency was very low over the last 100 years, each
      fire event was followed by drastic removal of spruce cover. Contrary to
      widespread belief of northward boreal forest expansion due to recent warming,
      lack of post-fire recovery during the last centuries, in comparison with active
      tree regeneration more than 1,000 years ago, indicates that the current climate
      does not favour such expansion.

PMID- 18048297
TI  - Sources of individual variation in plasma testosterone levels.
AB  - The steroid hormone testosterone (T) plays a central role in the regulation of
      breeding in males, because many physiological, morphological and behavioural
      traits related to reproduction are T dependent. Moreover, in many seasonally
      breeding vertebrates, male plasma T levels typically show a pronounced peak
      during the breeding season. While such population-level patterns are fairly well
      worked out, the sources and the implications of the large variability in
      individual T levels within the seasonal cycle remain surprisingly little
      understood. Understanding the potential sources of individual variation in T
      levels is important for behavioural and evolutionary ecologists, for at least two
      reasons. First, in 'honest signalling' theory, T is hypothesized to play a
      critical role as the assumed factor that enforces honesty of the expression of
      sexually selected quality indicators. Second, T is often considered a key
      mediator of central life-history trade-offs, such as investment in survival
      versus reproduction or in mating versus parental care. Here, we discuss the
      patterns of within- and between-individual variation in male plasma T levels in
      free-living populations of birds. We argue that it is unclear whether this
      variability mainly reflects differences in underlying individual quality
      (intrinsic factors such as genetic or maternal effects) or in the environment
      (extrinsic factors including time of day, individual territorial status and past
      experience). Research in avian behavioural endocrinology has mainly focused on
      the effects of extrinsic factors, while other sources of variance are often
      ignored. We suggest that studies that use an integrative approach and investigate
      the relative importance of all potential sources of variation are essential for
      the interpretation of data on individual plasma T levels.

PMID- 18048299
TI  - Trends in recent temperature and radial tree growth spanning 2000 years across
      northwest Eurasia.
AB  - This paper describes variability in trends of annual tree growth at several
      locations in the high latitudes of Eurasia, providing a wide regional comparison
      over a 2000-year period. The study focuses on the nature of local and widespread
      tree-growth responses to recent warming seen in instrumental observations,
      available in northern regions for periods ranging from decades to a century.
      Instrumental temperature data demonstrate differences in seasonal scale of
      Eurasian warming and the complexity and spatial diversity of tree-growing-season
      trends in recent decades. A set of long tree-ring chronologies provides empirical
      evidence of association between inter-annual tree growth and local, primarily
      summer, temperature variability at each location. These data show no evidence of
      a recent breakdown in this association as has been found at other high-latitude
      Northern Hemisphere locations. Using Kendall's concordance, we quantify the time
      dependent relationship between growth trends of the long chronologies as a group.
      This provides strong evidence that the extent of recent widespread warming across
      northwest Eurasia, with respect to 100- to 200-year trends, is unprecedented in
      the last 2000 years. An equivalent analysis of simulated temperatures using the
      HadCM3 model fails to show a similar increase in concordance expected as a
      consequence of anthropogenic forcing.

PMID- 18048300
TI  - Introduction. Integration of ecology and endocrinology in avian reproduction: a
      new synthesis.
AB  - Birds are some of the most familiar organisms of global ecosystems. Changes in
      the visibility and abundance of birds are therefore excellent indicators of
      population and physiological responses to habitat changes and are a major focus
      for public concern about detrimental environmental changes. In order to
      understand how birds respond to these challenges, it is essential to determine
      how the environment affects reproduction under natural conditions. The continuum
      from environmental variables (cues) to reproductive life-history traits depends
      upon a cascade of neural and physiological processes that determine the extent
      and rate at which birds will be able to adapt to changes in their environment.
      For a full understanding of this ability to adapt, ecologists and
      endocrinologists need to collaborate and build a common framework. The objective
      of this theme issue is to bring together a series of papers addressing how
      evolutionary ecologists and endocrinologists can collaborate directly using avian
      reproduction as a model system. First, we address the need to integrate ecology
      and endocrinology and what benefits to biological knowledge will be gained. The
      papers collected in this issue represent a new synthesis of ecology and
      endocrinology as discussed in three E-BIRD workshops. The three main foci are
      trade-offs and constraints, maternal effects and individual variation. Authors
      within each group present ecological and endocrinological aspects of their topics
      and many go on to outline testable hypotheses. Finally, we discuss where the
      major problems remain and how this issue points out where these need
      collaborative efforts of ecologists and endocrinologists. Specific challenges are
      raised to future researchers to break through intellectual barriers and explore
      new frontiers. This framework of topics will ultimately apply to all taxa because
      the principles involved are universal and hopefully will have direct application
      to programmes integrating organisms and genes throughout biological sciences.

PMID- 18048302
TI  - An artificial neural networks approach in managing healthcare.
AB  - Hospitals as learning organisations have evolved through complex phases of
      service failures and continuous service improvement to meet the business needs of
      a varied continuum of care customers. This paper explores the use of Artificial
      Neural Network (ANN) in the development of a decision support system to manage
      healthcare non-clinical services. The information (postal questionnaires and
      repertory grid interviews) used to develop the input to the National Healthcare
      Service Facilities Risk Exposure System (NHSFRES) was articulated from 60
      experienced healthcare operators. The system provides a reasonable early warning
      signal to the healthcare managers, and can be used by decision makers to evaluate
      the severity of risks on healthcare non clinical business operations. The
      advantage of using NHSFRES is that healthcare managers can provide their own risk
      assessment values (point score system) based on their own healthcare management
      business knowledge/judgement and corporate objectives.

PMID- 18048303
TI  - A subset polynomial neural networks approach for breast cancer diagnosis.
AB  - Breast cancer is a very common and serious cancer for women that is diagnosed in
      one of every eight Australian women before the age of 85. The conventional method
      of breast cancer diagnosis is mammography. However, mammography has been reported
      to have poor diagnostic capability. In this paper we have used subset polynomial
      neural network techniques in conjunction with fine needle aspiration cytology to
      undertake this difficult task of predicting breast cancer. The successful
      findings indicate that adoption of NNs is likely to lead to increased survival of
      women with breast cancer, improved electronic healthcare, and enhanced quality of
      life.

PMID- 18048301
TI  - Early growth conditions, phenotypic development and environmental change.
AB  - Phenotypic development is the result of a complex interplay involving the
      organism's own genetic make-up and the environment it experiences during
      development. The latter encompasses not just the current environment, but also
      indirect, and sometimes lagged, components that result from environmental effects
      on its parents that are transmitted to their developing offspring in various ways
      and at various stages. These environmental effects can simply constrain
      development, for example, where poor maternal condition gives rise to poorly
      provisioned, low-quality offspring. However, it is also possible that
      environmental circumstances during development shape the offspring phenotype in
      such a way as to better prepare it for the environmental conditions it is most
      likely to encounter during its life. Studying the extent to which direct and
      indirect developmental responses to environmental effects are adaptive requires
      clear elucidation of hypotheses and careful experimental manipulations. In this
      paper, I outline how the different paradigms applied in this field relate to each
      other, the main predictions that they produce and the kinds of experimental data
      needed to distinguish among competing hypotheses. I focus on birds in particular,
      but the theories discussed are not taxon specific. Environmental influences on
      phenotypic development are likely to be mediated, in part at least, by endocrine
      systems. I examine evidence from mechanistic and functional avian studies and
      highlight the general areas where we lack key information.

PMID- 18048304
TI  - Design of wearable cardiac telemedicine system.
AB  - Cardiovascular disease is the world's leading killer disease, accounting for 16.7
      million deaths annually. About 22 million people all over the world run the risk
      of sudden heart failure. However, deaths from cardiovascular diseases have
      decreased substantially over the past two decades, largely as a result of
      advances in acute care and cardiac surgery. These developments have resulted in a
      growing population of patients who have survived myocardial infarction. These
      patients need to be continuously monitored so that the initiation of treatment
      can be taken up within the crucial golden hour. The available conventional
      methods of monitoring restrict the mobility of these patients within a hospital
      or room. The primary aim of this paper is to design a Wearable Cardiac
      Telemedicine System that can help the mobility of patients, so as to regain their
      independence and return to an active social or work schedule, thereby improving
      their psychological well-being. The whole system has been implemented and tested.
      The results obtained are encouraging.

PMID- 18048305
TI  - Using actor network theory to understand network centric healthcare operations.
AB  - The adoption and diffusion of e-health and the application of ICT in healthcare
      is being heralded as the panacea with both European and US governments making e
      health a priority on their agendas. In this context, a model of networkcentric
      healthcare operations has been proffered as the best way to maximise the benefits
      of ICT use in healthcare. We suggest that, before we can move forward and realise
      such a state, it is vital to examine the critical issues, likely barriers and
      facilitators and, most importantly, the critical success factors. To do this
      however, we need an appropriate cognitive lens through which we can capture all
      the complexities of healthcare dynamics. In this paper we suggest why Actor
      Network Theory (ANT) should be this lens.

PMID- 18048306
TI  - Chronic disease management and the development of virtual communities.
AB  - The current volume and expected increases in the number of patients with chronic
      diseases are concerned significant and substantial. Patients with chronic
      diseases have a great need to personally manage their health-related behaviour,
      such as food consumption, and its impact on their health indicators, like blood
      pressure, body weight, blood sugar, cholesterol, to name a few. Current
      healthcare systems are unable to meet the needs of patients with chronic diseases
      for management, due to the need for acute care. An analysis of the needs was
      performed and recommendations for virtual communities were made to help patients
      with chronic diseases monitor and manage their health. Virtual communities have
      the potential to meet the need to assist with monitoring activities, education,
      community membership, and the sale of products and services. However, they also
      face risks inherent to accepting and storing any form of personal health
      information, and of remaining in compliance with the Health Insurance Portability
      and Accessibility Act of 2001.

PMID- 18048307
TI  - Customer relationship management in the contract pharmaceutical industry: an
      exploratory study for measuring success.
AB  - Managing customer relationships is a very important issue in business-to-business
      markets. This research investigates the growing number of available resources
      defining Customer Relationship Management (CRM) efforts, and how they are being
      applied within the Contract Pharmaceutical Manufacturing industry. Exploratory
      study results using face-to-face and telephone questionnaires based on four
      criteria for rating a company's CRM efforts are presented. Data was collected
      from large Contract Pharmaceutical Manufacturing companies in the US market. The
      results and conclusions are discussed relating how the Contract Pharmaceutical
      Manufacturing industry is implementing CRM including some potential steps to take
      when considering a CRM initiative.

PMID- 18048308
TI  - The major barriers and facilitators for the adoption and implementation of
      knowledge management in healthcare operations.
AB  - The importance of Knowledge Management (KM) to organisations in today's
      competitive environment is being recognised as paramount and significant. This is
      particularly evident for healthcare both globally and in the USA. The US
      healthcare system is facing numerous challenges in trying to deliver cost
      effective, high quality treatments and is turning to KM techniques and
      technologies for solutions in an attempt to achieve this goal. We examine this by
      outlining the primary barriers encountered in the adoption and implementation of
      specific KM technologies in healthcare settings and then examine these in the
      context of an orthopaedic case vignette. In doing so, we show the benefit of KM
      tools and techniques for enhancing healthcare delivery.

PMID- 18048309
TI  - How workflow management systems enable the achievement of value driven healthcare
      delivery.
AB  - Healthcare institutions globally are currently having major problems accessing
      and maintaining the large amounts of data that are continuously being generated.
      Examination of the clinical procedures relating to patient management reveals
      that many of these activities are repetitive. Workflow Management Systems (WFMS)
      can automate these repeated activities. Moreover, the introduction of WFMS would
      enable healthcare institutions to face this challenge of transforming large
      amounts of medical data into contextually relevant clinical information and
      knowledge. In order to emphasise the dynamic connection between healthcare,
      workflow and internet technologies, the intelligence continuum is introduced.

PMID- 18048310
TI  - Proteomic data mining using predicted peptide chromatographic retention times.
AB  - Correct identification of proteins from peptide fragments is important for
      proteomic analyses. Peptides are initially separated by Reversed-Phase High
      Performance Liquid Chromatography (RP-HPLC) before Mass Spectrometry (MS)
      identification. At the present time, peptide fragment retention (separation) time
      is not used as a useful scoring filter for identification of the peptide
      fragments and their parent proteins. In the present paper, we present a new web
      based tool for the prediction of peptide fragment retention times and its use in
      compiling a database of approximately 133,000 peptide fragments computationally
      obtained by digestion with trypsin of 4,265 E. coli - K12 proteins. The retention
      calculation is based on the described formulae and the fragments/protein
      identification was carried out using a simple search-scoring algorithm.

PMID- 18048311
TI  - On predicting secondary structure transition.
AB  - A function of a protein is dependent on its structure; therefore, predicting a
      protein structure from an amino acid sequence is an active area of research. To
      improve the accuracy of validation of structures, we are studying the
      predictability of secondary structure transitions using the following machine
      learning algorithms: naive Bayes, C4.5 decision tree, and random forest. The
      annotated data sets from PDB that have agreement with DSSP and STRIDE are used
      for training and testing. We have demonstrated that predicting structure
      transition with high degree of certainty is possible and we were able to get as
      high as 97.5% of prediction accuracy.

PMID- 18048312
TI  - Molecular coevolution of the vertebrate cytochrome c(1) and Rieske iron sulphur
      protein in the cytochrome bc(1) complex.
AB  - Cytochrome c(1) (cyt-c(1)) and the Rieske Iron Sulphur Protein (ISP) are subunits
      of the cytochrome bc(1) complex located in the mitochondria functioning both as a
      proton pump and an electron transporter. Vertebrate model organism phylogenies
      were used in conjunction with existing 3D protein structures to evaluate the
      biochemical evolution of cyt-c(1) and ISP in terms of selection on amino acid
      properties. We found selection acting on the exterior surfaces of both proteins
      and specifically the core region of cyt-c(1). There is evidence supporting
      coevolution of these proteins relative to alpha helical tendencies,
      compressibility and equilibrium constant.

PMID- 18048313
TI  - Pharmacogenomics: analysing SNPs in the CYP2D6 gene using amino acid properties.
AB  - The CYP2D6 gene is responsible for metabolising a large portion of the commonly
      prescribed drugs. Because of its importance, various approaches have been taken
      to analyse CYP2D6 and Single Nucleotide Polymorphisms (SNPs) throughout its
      sequence. This study introduces a novel method to analyse the effects of SNPs on
      encoded protein complexes by focusing on the biochemical properties of each non
      synonymous substitution using the program TreeSAAP. Our results show four SNPs in
      CYP2D6 that exhibit radical changes in amino acid properties which may cause a
      lack of functionality in the CYP2D6 gene and contribute to a person's inability
      to metabolise specific drugs.

PMID- 18048314
TI  - Inferring protein-protein interaction networks from protein complex data.
AB  - Present day approaches for the determination of protein-protein interaction
      networks are usually based on two hybrid experimental measurements. Here we
      consider a computational method that uses another type of experimental data:
      instead of direct information about protein-protein interactions, we consider
      data in the form of protein complexes. We propose a method for using these
      complexes to provide predictions of protein-protein interactions. When applied to
      a dataset obtained from a cat melanoma cell line we find that we are able to
      predict when a protein pair belongs to a complex with approximately 96% accuracy.
      Further, we are able to extrapolate the experimentally identified interaction
      pairs to the entire cat proteome.

PMID- 18048315
TI  - Phylogenies scores for exhaustive searches and parsimony scores searches.
AB  - Fundamental to Multiple Sequence Alignment (MSA) algorithms is modelling
      insertions and deletions (gaps). The most prevalent model is to use Gap Open
      Penalties (GOP) and Gap Extension Penalties (GEP). While GOP and GEP are well
      understood conceptually, their effects on MSA and consequently on phylogeny
      scores are not as well understood. We use exhaustive phylogeny searching to
      explore the effects of varying the GOP and GEP for three nuclear ribosomal data
      sets. Particular attention is given to optimal maximum likelihood and parsimony
      phylogeny scores for various alignments of a range of GOP and GEP and their
      respective distribution of phylogeny scores.

PMID- 18048316
TI  - Evolutionary selective pressure on three mitochondrial SNPs is consistent with
      their influence on metabolic efficiency in Pima Indians.
AB  - We investigated whether the effect of evolutionary selection on three recent
      Single Nucleotide Polymorphisms (SNPs) in the mitochondrial sub-haplogroups of
      Pima Indians is consistent with their effects on metabolic efficiency. The
      mitochondrial SNPs impact metabolic rate and respiratory quotient, and may be
      adaptations to caloric restriction in a desert habitat. Using TreeSAAP software,
      we examined evolutionary selection in 107 mammalian species at these SNPs,
      characterising the biochemical shifts produced by the amino acid substitutions.
      Our results suggest that two SNPs were affected by selection during mammalian
      evolution in a manner consistent with their effects on metabolic efficiency in
      Pima Indians.

PMID- 18048317
TI  - A study of the repetitive structure and distribution of short motifs in human
      genomic sequences.
AB  - Over the last several years the search for functional genomic elements by
      exploiting motif over-representation became increasingly popular. However, about
      half of the human genome is repetitive, and that is also the case with most
      higher eukaryotes. In this study we have shown that in addition to these known
      repeats, human sequences feature many short over-represented motifs, and that
      their frequency varies only slightly between random repeat-masked sequences and
      regions located immediately upstream of the known genes. Most of our study has
      been performed on the ENCODE sequences, which comprise about 1% of the human
      genome.

PMID- 18048318
TI  - Conservative adjustment of permutation p-values when the number of permutations
      is limited.
AB  - In this study, we show through the theory of order statistics that a considerable
      proportion of p-values will be under-evaluated by the permutation procedure. To
      solve this problem, we propose to conservatively adjust permutation p-values. The
      adjustment requires no parametric assumption on the distribution of test
      statistics. The solution can be expressed by a normalised incomplete beta
      function. The related normal distribution approximation is also discussed.
      Simulations are conducted to illustrate the proposed method and two microarray
      gene expression data sets are considered for applications.

PMID- 18048319
TI  - Savanna chimpanzees dig for food.

PMID- 18048321
TI  - Mechanoenzymes under superstall and large assisting loads reveal structural
      features.
AB  - Single-molecule experiments on the motor protein kinesin have observed runs of
      backsteps and thus a negative, that is, reverse mean velocity, V, under
      superstall loads, F; but, counterintuitively, beyond stall, V(F) displays a
      shallow minimum and then decreases in magnitude. Conversely, under assisting
      loads V(F) rises to a maximum before decreasing monotonically. By contrast, while
      the velocity of myosin V also saturates under assisting loads, the motor moves
      backward increasingly rapidly under superstall loads. For both kinesin and myosin
      V this behavior is implied remarkably well by simple two-state kinetic models
      when extrapolated to large loads. To understand the origins of such results in
      general mechanoenzymes, biochemical kinetic descriptions are discussed on the
      basis of a free-energy landscape picture. It transpires that the large-load
      performance is determined by the geometrical placement of the intermediate
      mechanochemical states of the enzymatic cycles relative to the associated
      transition states. Explicit criteria are presented for N-state sequential
      kinetics, including side-reaction chains, etc., and for parallel-pathway models.
      Physical colocalization of biochemically distinct states generally implies large
      load velocity saturation.

PMID- 18048320
TI  - Mononeme: a new secretory organelle in Plasmodium falciparum merozoites
      identified by localization of rhomboid-1 protease.
AB  - Compartmentalization of proteins into subcellular organelles in eukaryotic cells
      is a fundamental mechanism of regulating complex cellular functions. Many
      proteins of Plasmodium falciparum merozoites involved in invasion are
      compartmentalized into apical organelles. We have identified a new merozoite
      organelle that contains P. falciparum rhomboid-1 (PfROM1), a protease that
      cleaves the transmembrane regions of proteins involved in invasion. By
      immunoconfocal microscopy, PfROM1 was localized to a single, thread-like
      structure on one side of the merozoites that appears to be in close proximity to
      the subpellicular microtubules. PfROM1 was not found associated with micronemes,
      rhoptries, or dense granules, the three identified secretory organelles of
      invasion. Release of merozoites from schizonts resulted in the movement of PfROM1
      from the lateral asymmetric localization to the merozoite apical pole and the
      posterior pole. We have named this single thread-like organelle in merozoites,
      the mononeme.

PMID- 18048322
TI  - A forest-based approach to identifying gene and gene gene interactions.
AB  - Multiple genes, gene-by-gene interactions, and gene-by-environment interactions
      are believed to underlie most complex diseases. However, such interactions are
      difficult to identify. Although there have been recent successes in identifying
      genetic variants for complex diseases, it still remains difficult to identify
      gene-gene and gene-environment interactions. To overcome this difficulty, we
      propose a forest-based approach and a concept of variable importance. The
      proposed approach is demonstrated by simulation study for its validity and
      illustrated by a real data analysis for its use. Analyses of both real data and
      simulated data based on published genetic models show the effectiveness of our
      approach. For example, our analysis of a published data set on age-related
      macular degeneration (AMD) not only confirmed a known genetic variant (P value =
      2E-6) for AMD, but also revealed an unreported haplotype surrounding single
      nucleotide polymorphism (SNP) rs10272438 on chromosome 7 that was significantly
      associated with AMD (P value = 0.0024). These significance levels are obtained
      after the consideration for a large number of SNPs. Thus, the importance of this
      work is twofold: it proposes a powerful and flexible method to identify high-risk
      haplotypes and their interactions and reveals a potentially protective variant
      for AMD.

PMID- 18048323
TI  - A helix-breaking mutation in TRPML3 leads to constitutive activity underlying
      deafness in the varitint-waddler mouse.
AB  - Homozygote varitint-waddler (Va) mice, expressing a mutant isoform (A419P) of
      TRPML3 (mucolipin 3), are profoundly deaf and display vestibular and pigmentation
      deficiencies, sterility, and perinatal lethality. Here we show that the varitint
      waddler isoform of TRPML3 carrying an A419P mutation represents a constitutively
      active cation channel that can also be identified in native varitint-waddler hair
      cells as a distinct inwardly rectifying current. We hypothesize that the
      constitutive activation of TRPML3 occurs as a result of a helix-breaking proline
      substitution in transmembrane-spanning domain 5 (TM5). A proline substitution
      scan demonstrated that the inner third of TRPML3's TM5 is highly susceptible to
      proline-based kinks. Proline substitutions in TM5 of other TRP channels revealed
      that TRPML1, TRPML2, TRPV5, and TRPV6 display a similar susceptibility at
      comparable positions, whereas other TRP channels were not affected. We conclude
      that the molecular basis for deafness in the varitint-waddler mouse is the result
      of hair cell death caused by constitutive TRPML3 activity. To our knowledge, our
      study provides the first direct mechanistic link of a mutation in a TRP ion
      channel with mammalian hearing loss.

PMID- 18048324
TI  - Acute-phase protein alpha-1-acid glycoprotein mediates neutrophil migration
      failure in sepsis by a nitric oxide-dependent mechanism.
AB  - The reduction of circulating neutrophil migration to infection sites is
      associated with a poor outcome of severe sepsis. alpha-1-Acid glycoprotein (AGP)
      was isolated from the sera of severely septic patients by HPLC and acrylamide gel
      electrophoresis and identified by mass spectrometry. Both the isolated protein
      and commercial AGP inhibited carrageenin-induced neutrophil migration into the
      rat peritoneal cavity when administered i.v. at a dose of 4.0 microg per rat (95
      pmol per rat). Analysis by intravital microscopy demonstrated that both proteins
      inhibited the rolling and adhesion of leukocytes in the mesenteric
      microcirculation. The inhibitory activity was blocked by 50 mg/kg aminoguanidine,
      s.c., and was not demonstrable in inducible nitric oxide synthase (iNOS) knockout
      mice. Incubation of AGP with neutrophils from healthy subjects induced the
      production of NO and inhibited the neutrophil chemotaxis by an iNOS/NO/cyclic
      guanosine 3,5-monophosphate-dependent pathway. In addition, AGP induced the l
      selectin shedding by neutrophils. The administration of AGP to rats with mild
      cecal ligation puncture sepsis inhibited neutrophil migration and reduced 7-day
      survival from approximately 80% to 20%. These data demonstrate that AGP, an acute
      phase protein, inhibits neutrophil migration by an NO-dependent process and
      suggest that AGP also participates in human sepsis.

PMID- 18048325
TI  - Vitamin B1 biosynthesis in plants requires the essential iron sulfur cluster
      protein, THIC.
AB  - Vitamin B1 (thiamin) is an essential compound in all organisms acting as a
      cofactor in key metabolic reactions and has furthermore been implicated in
      responses to DNA damage and pathogen attack in plants. Despite the fact that it
      was discovered almost a century ago and deficiency is a widespread health
      problem, much remains to be deciphered about its biosynthesis. The vitamin is
      composed of a thiazole and pyrimidine heterocycle, which can be synthesized by
      prokaryotes, fungi, and plants. Plants are the major source of the vitamin in the
      human diet, yet little is known about the biosynthesis of the compound therein.
      In particular, it has never been verified whether the pyrimidine heterocycle is
      derived from purine biosynthesis through the action of the THIC protein as in
      bacteria, rather than vitamin B6 and histidine as demonstrated for fungi. Here,
      we identify a homolog of THIC in Arabidopsis and demonstrate its essentiality not
      only for vitamin B1 biosynthesis, but also plant viability. This step takes place
      in the chloroplast and appears to be regulated at several levels, including
      through the presence of a riboswitch in the 3'-untranslated region of THIC.
      Strong evidence is provided for the involvement of an iron-sulfur cluster in the
      remarkable chemical rearrangement reaction catalyzed by the THIC protein for
      which there is no chemical precedent. The results suggest that vitamin B1
      biosynthesis in plants is in fact more similar to prokaryotic counterparts and
      that the THIC protein is likely to be the key regulatory protein in the pathway.

PMID- 18048326
TI  - Identification of retinoic acid as an inhibitor of transcription factor Nrf2
      through activation of retinoic acid receptor alpha.
AB  - Isothiocyanates and phenolic antioxidants can prevent cancer through activation
      of Nrf2 (NF-E2 p45-related factor 2), a transcription factor that controls
      expression of cytoprotective genes through the antioxidant response element (ARE)
      enhancer. Using a human mammary MCF7-derived AREc32 reporter cell line, we now
      report that all-trans retinoic acid (ATRA), and other retinoic acid receptor
      alpha (RARalpha) agonists, markedly reduces the ability of Nrf2 to mediate
      induction of ARE-driven genes by cancer chemopreventive agents including the
      metabolite of butylated hydroxyanisole, tert-butylhydroquinone (tBHQ). The basal
      and tBHQ-inducible expression of aldo-keto reductase (AKR) AKR1C1 and AKR1C2
      genes, which are regulated by Nrf2, was also repressed by ATRA in AREc32 cells.
      Antagonists of RARalpha augmented induction of ARE-driven gene expression by
      tBHQ, as did knockdown of RARalpha by using RNAi. The expression of the ARE-gene
      battery was increased in the small intestine of mice fed on a vitamin A-deficient
      diet, and this increase was repressed by administration of ATRA. By contrast, in
      the small intestine of Nrf2 null mice, the expression of ARE-driven genes was not
      affected by vitamin A status. In MCF7 cells, ATRA did not block the nuclear
      accumulation of Nrf2 but reduced the binding of Nrf2 to the ARE enhancer as a
      consequence of forming a complex with RARalpha. These data suggest that cross
      talk between Nrf2 and RARalpha could markedly influence the sensitivity of cells
      to electrophiles and oxidative stressors and, as a consequence, to
      carcinogenesis.

PMID- 18048327
TI  - Axial ligand tuning of a nonheme iron(IV)-oxo unit for hydrogen atom abstraction.
AB  - The reactivities of mononuclear nonheme iron(IV)-oxo complexes bearing different
      axial ligands, [Fe(IV)(O)(TMC)(X)](n+) [where TMC is 1,4,8,11-tetramethyl
      1,4,8,11-tetraazacyclotetradecane and X is NCCH(3) (1-NCCH(3)), CF(3)COO(-) (1
      OOCCF(3)), or N(3)(-) (1-N(3))], and [Fe(IV)(O)(TMCS)](+) (1'-SR) (where TMCS is
      1-mercaptoethyl-4,8,11-trimethyl-1,4,8,11-tetraazacyclotetradecane), have been
      investigated with respect to oxo-transfer to PPh(3) and hydrogen atom abstraction
      from phenol O H and alkylaromatic C H bonds. These reactivities were
      significantly affected by the identity of the axial ligands, but the reactivity
      trends differed markedly. In the oxidation of PPh(3), the reactivity order of 1
      NCCH(3) > 1-OOCCF(3) > 1-N(3) > 1'-SR was observed, reflecting a decrease in the
      electrophilicity of iron(IV)-oxo unit upon replacement of CH(3)CN with an anionic
      axial ligand. Surprisingly, the reactivity order was inverted in the oxidation of
      alkylaromatic C H and phenol O H bonds, i.e., 1'-SR > 1-N(3) > 1-OOCCF(3) > 1
      NCCH(3). Furthermore, a good correlation was observed between the reactivities of
      iron(IV)-oxo species in H atom abstraction reactions and their reduction
      potentials, E(p,c), with the most reactive 1'-SR complex exhibiting the lowest
      potential. In other words, the more electron-donating the axial ligand is, the
      more reactive the iron(IV)-oxo species becomes in H atom abstraction. Quantum
      mechanical calculations show that a two-state reactivity model applies to this
      series of complexes, in which a triplet ground state and a nearby quintet excited
      state both contribute to the reactivity of the complexes. The inverted reactivity
      order in H atom abstraction can be rationalized by a decreased triplet-quintet
      gap with the more electron-donating axial ligand, which increases the
      contribution of the much more reactive quintet state and enhances the overall
      reactivity.

PMID- 18048328
TI  - Delayed leaf senescence induces extreme drought tolerance in a flowering plant.
AB  - Drought, the most prominent threat to agricultural production worldwide,
      accelerates leaf senescence, leading to a decrease in canopy size, loss in
      photosynthesis and reduced yields. On the basis of the assumption that senescence
      is a type of cell death program that could be inappropriately activated during
      drought, we hypothesized that it may be possible to enhance drought tolerance by
      delaying drought-induced leaf senescence. We generated transgenic plants
      expressing an isopentenyltransferase gene driven by a stress- and maturation
      induced promoter. Remarkably, the suppression of drought-induced leaf senescence
      resulted in outstanding drought tolerance as shown by, among other responses,
      vigorous growth after a long drought period that killed the control plants. The
      transgenic plants maintained high water contents and retained photosynthetic
      activity (albeit at a reduced level) during the drought. Moreover, the transgenic
      plants displayed minimal yield loss when watered with only 30% of the amount of
      water used under control conditions. The production of drought-tolerant crops
      able to grow under restricted water regimes without diminution of yield would
      minimize drought-related losses and ensure food production in water-limited
      lands.

PMID- 18048329
TI  - ID genes mediate tumor reinitiation during breast cancer lung metastasis.
AB  - The establishment of distant metastases depends on the capacity of small numbers
      of cancer cells to regenerate a tumor after entering a target tissue. The
      mechanisms that confer this capacity remain to be defined. Here we identify a
      role for the transcriptional inhibitors of differentiation Id1 and Id3 as
      selective mediators of lung metastatic colonization in the triple negative [TN,
      i.e., lacking expression of estrogen receptor and progesterone receptor, and
      lacking Her2 (human epidermal growth factor receptor 2) amplification] subgroup
      of human breast cancer. Although broad expression of Id1 has recently been
      documented in tumors of the rare metaplastic subtype, here we report that rare
      Id1-expressing cells are also present in the more common TN subset of human
      breast tumors but not in other subtypes. We also provide evidence that Id1
      expression is enriched in clinically obtained hormone receptor negative lung
      metastases. Functional studies demonstrate that Id1 and its closely related
      family member Id3 are required for tumor initiating functions, both in the
      context of primary tumor formation and during metastatic colonization of the lung
      microenvironment. In vivo characterization of lung metastatic progression reveals
      that Id1 and Id3 facilitate sustained proliferation during the early stages of
      metastatic colonization, subsequent to extravasation into the lung parenchyma.
      These results shed light on the proliferative mechanisms that initiate metastatic
      colonization, and they implicate Id1 and Id3 as mediators of this malignant
      function in the TN subgroup of breast cancers.

PMID- 18048330
TI  - Analysis of 81 genes from 64 plastid genomes resolves relationships in
      angiosperms and identifies genome-scale evolutionary patterns.
AB  - Angiosperms are the largest and most successful clade of land plants with
      >250,000 species distributed in nearly every terrestrial habitat. Many
      phylogenetic studies have been based on DNA sequences of one to several genes,
      but, despite decades of intensive efforts, relationships among early diverging
      lineages and several of the major clades remain either incompletely resolved or
      weakly supported. We performed phylogenetic analyses of 81 plastid genes in 64
      sequenced genomes, including 13 new genomes, to estimate relationships among the
      major angiosperm clades, and the resulting trees are used to examine the
      evolution of gene and intron content. Phylogenetic trees from multiple methods,
      including model-based approaches, provide strong support for the position of
      Amborella as the earliest diverging lineage of flowering plants, followed by
      Nymphaeales and Austrobaileyales. The plastid genome trees also provide strong
      support for a sister relationship between eudicots and monocots, and this group
      is sister to a clade that includes Chloranthales and magnoliids. Resolution of
      relationships among the major clades of angiosperms provides the necessary
      framework for addressing numerous evolutionary questions regarding the rapid
      diversification of angiosperms. Gene and intron content are highly conserved
      among the early diverging angiosperms and basal eudicots, but 62 independent gene
      and intron losses are limited to the more derived monocot and eudicot clades.
      Moreover, a lineage-specific correlation was detected between rates of nucleotide
      substitutions, indels, and genomic rearrangements.

PMID- 18048331
TI  - Clinical implications of the loss of vasoactive nitric oxide during red blood
      cell storage.

PMID- 18048332
TI  - Parallel genomic evolution and metabolic interdependence in an ancient symbiosis.
AB  - Obligate symbioses with nutrient-provisioning bacteria have originated often
      during animal evolution and have been key to the ecological diversification of
      many invertebrate groups. To date, genome sequences of insect nutritional
      symbionts have been restricted to a related cluster within Gammaproteobacteria
      and have revealed distinctive features, including extreme reduction, rapid
      evolution, and biased nucleotide composition. Using recently developed sequencing
      technologies, we show that Sulcia muelleri, a member of the Bacteroidetes,
      underwent similar genomic changes during coevolution with its sap-feeding insect
      host (sharpshooters) and the coresident symbiont Baumannia cicadellinicola
      (Gammaproteobacteria). At 245 kilobases, Sulcia's genome is approximately one
      tenth of the smallest known Bacteroidetes genome and among the smallest for any
      cellular organism. Analysis of the coding capacities of Sulcia and Baumannia
      reveals striking complementarity in metabolic capabilities.

PMID- 18048333
TI  - The all-trans-retinal dimer series of lipofuscin pigments in retinal pigment
      epithelial cells in a recessive Stargardt disease model.
AB  - The bis-retinoid pigments that accumulate in retinal pigment epithelial cells as
      lipofuscin are associated with inherited and age-related retinal disease. In
      addition to A2E and related cis isomers, we previously showed that condensation
      of two molecules of all-trans-retinal leads to the formation of a protonated
      Schiff base conjugate, all-trans-retinal dimer-phosphatidylethanolamine. Here we
      report the characterization of the related pigments, all-trans-retinal dimer
      ethanolamine and unconjugated all-trans-retinal dimer, in human and mouse retinal
      pigment epithelium. In eyecups of Abcr(-/-) mice, a model of recessive Stargardt
      macular degeneration, all-trans-retinal dimer-phosphatidylethanolamine was
      increased relative to wild type and was more abundant than A2E. Total pigment of
      the all-trans-retinal dimer series (sum of all-trans-retinal dimer
      phosphatidylethanolamine, all-trans-retinal dimer-ethanolamine, and all-trans
      retinal dimer) increased with age in Abcr(-/-) mice and was modulated by amino
      acid variants in Rpe65. In in vitro assays, enzyme-mediated hydrolysis of all
      trans-retinal dimer-phosphatidylethanolamine generated all-trans-retinal dimer
      ethanolamine, and protonation/deprotonation of the Schiff base nitrogen of all
      trans-retinal dimer-ethanolamine was pH-dependent. Unconjugated all-trans-retinal
      dimer was a more efficient generator of singlet oxygen than A2E, and the all
      trans-retinal dimer series was more reactive with singlet oxygen than was A2E. By
      analyzing chromatographic properties and UV-visible spectra together with mass
      spectrometry, mono- and bis-oxygenated all-trans-retinal dimer photoproducts were
      detected in Abcr(-/-) mice. The latter findings are significant to an
      understanding of the adverse effects of retinal pigment epithelial cell
      lipofuscin.

PMID- 18048334
TI  - Using plastid genome-scale data to resolve enigmatic relationships among basal
      angiosperms.
AB  - Although great progress has been made in clarifying deep-level angiosperm
      relationships, several early nodes in the angiosperm branch of the Tree of Life
      have proved difficult to resolve. Perhaps the last great question remaining in
      basal angiosperm phylogeny involves the branching order among the five major
      clades of mesangiosperms (Ceratophyllum, Chloranthaceae, eudicots, magnoliids,
      and monocots). Previous analyses have found no consistent support for
      relationships among these clades. In an effort to resolve these relationships, we
      performed phylogenetic analyses of 61 plastid genes ( approximately 42,000 bp)
      for 45 taxa, including members of all major basal angiosperm lineages. We also
      report the complete plastid genome sequence of Ceratophyllum demersum. Parsimony
      analyses of combined and partitioned data sets varied in the placement of several
      taxa, particularly Ceratophyllum, whereas maximum-likelihood (ML) trees were more
      topologically stable. Total evidence ML analyses recovered a clade of
      Chloranthaceae + magnoliids as sister to a well supported clade of monocots +
      (Ceratophyllum + eudicots). ML bootstrap and Bayesian support values for these
      relationships were generally high, although approximately unbiased topology tests
      could not reject several alternative topologies. The extremely short branches
      separating these five lineages imply a rapid diversification estimated to have
      occurred between 143.8 +/- 4.8 and 140.3 +/- 4.8 Mya.

PMID- 18048335
TI  - Human papillomaviruses activate caspases upon epithelial differentiation to
      induce viral genome amplification.
AB  - The life cycle of human papillomaviruses (HPVs) is linked to epithelial
      differentiation, with late viral events restricted to the uppermost stratified
      layers. Our studies indicated that HPV activates capases-3, -7, and -9 upon
      differentiation, whereas minimal activation was observed in differentiating
      normal keratinocytes. Activation occurred in the absence of significant levels of
      apoptosis, suggesting a potential role for caspases in the viral life cycle. In
      support of this, the addition of caspase inhibitors significantly impaired
      differentiation-dependent viral genome amplification. A conserved caspase
      cleavage motif was identified in the replication protein E1 ((46)DxxD(49)) that
      was targeted in vitro by both recombinant caspase-3 and caspase-7. Mutation of
      this site inhibited amplification of viral genomes, indicating that caspase
      cleavage is necessary for the productive viral life cycle. Our study demonstrates
      that HPV activates caspases upon differentiation to facilitate productive viral
      replication and represents a way by which HPV controls viral gene function in
      differentiating cells.

PMID- 18048336
TI  - Redundant and unique roles of retinol dehydrogenases in the mouse retina.
AB  - Highly abundant short-chain alcohol dehydrogenases (RDHs) in the retina were
      assumed to be involved in the recycling of 11-cis-retinal chromophore in the
      visual cycle. Mutations in human RDH genes are associated with Fundus
      albipunctatus, a mild form of night blindness (RDH5) and an autosomal recessive,
      childhood-onset severe retinal dystrophy (RDH12). Rdh12 knockout mice were found
      to be susceptible to light-induced photoreceptor apoptosis, whereas Rdh5 and Rdh8
      knockout mice displayed only delayed dark adaptation. However, each knockout
      mouse eventually regenerated normal levels of visual pigments, suggesting that
      RDHs compensate for each other in the visual cycle. Here, we established RDH
      double knockout (Rdh8(-/-)Rdh12(-/-)) and triple knockout (Rdh5(-/-)Rdh8(-/
      )Rdh12(-/-)) mice generated on various genetic backgrounds including a rod alpha
      transducin knockout to test cone function. RDH activity was severely reduced in
      Rdh8(-/-)Rdh12(-/-) retina extracts, whereas Rdh8(-/-) RDH activity was
      intermediate and Rdh12(-/-) RDH activity was reduced only slightly. Surprisingly,
      all multiple knockout mice produced sufficient amounts of the chromophore to
      regenerate rhodopsin and cone pigments in vivo. Three-month-old Rdh8(-/-)Rdh12(-/
      ) mice characteristically displayed a slowly progressing rod-cone dystrophy
      accompanied by accumulation of N-retinylidene-N-retinylethanolamine (A2E), a
      toxic substance known to contribute to retinal degeneration. A2E accumulation and
      retinal degeneration were prevented by application of retinylamine, a potent
      retinoid cycle inhibitor. The results suggest that RDH8 and RDH12 are dispensable
      in support of the visual cycle but appear to be key components in clearance of
      free all-trans-retinal, thereby preventing A2E accumulation and photoreceptor
      cell death.

PMID- 18048337
TI  - Phloem loading in Verbascum phoeniceum L. depends on the synthesis of raffinose
      family oligosaccharides.
AB  - Phloem loading is the initial step in photoassimilate export and the one that
      creates the driving force for mass flow. It has been proposed that loading occurs
      symplastically in species that translocate carbohydrate primarily as raffinose
      family oligosaccharides (RFOs). In these plants, dense fields of plasmodesmata
      connect bundle sheath cells to specialized companion cells (intermediary cells)
      in the minor veins. According to the polymer trap model, advanced as a mechanism
      of symplastic loading, sucrose from the mesophyll diffuses into intermediary
      cells and is converted there to RFOs. This process keeps the sucrose
      concentration low and, because of the larger size of the RFOs, prevents back
      diffusion. To test this model, the RFO pathway was down-regulated in Verbascum
      phoeniceum L. by suppressing the synthesis of galactinol synthase (GAS), which
      catalyzes the first committed step in RFO production. Two GAS genes (VpGAS1 and
      VpGAS2) were cloned and shown to be expressed in intermediary cells. Simultaneous
      RNAi suppression of both genes resulted in pronounced inhibition of RFO
      synthesis. Phloem transport was negatively affected, as evidenced by the
      accumulation of carbohydrate in the lamina and the reduced capacity of leaves to
      export sugars during a prolonged dark period. In plants with severe down
      regulation, additional symptoms of reduced export were obvious, including
      impaired growth, leaf chlorosis, and necrosis and curling of leaf margins.

PMID- 18048338
TI  - Mitochondrial origin-binding protein UMSBP mediates DNA replication and
      segregation in trypanosomes.
AB  - Kinetoplast DNA (kDNA) is the remarkable mitochondrial genome of trypanosomatids.
      Its major components are several thousands of topologically linked DNA
      minicircles, whose replication origins are bound by the universal minicircle
      sequence-binding protein (UMSBP). The cellular function of UMSBP has been studied
      in Trypanosoma brucei by using RNAi analysis. Silencing of the trypanosomal UMSBP
      genes resulted in remarkable effects on the trypanosome cell cycle. It
      significantly inhibited the initiation of minicircle replication, blocked nuclear
      DNA division, and impaired the segregation of the kDNA network and the flagellar
      basal body, resulting in growth arrest. These observations, revealing the
      function of UMSBP in kDNA replication initiation and segregation as well as in
      mitochondrial and nuclear division, imply a potential role for UMSBP in linking
      kDNA replication and segregation to the nuclear S-phase control during the
      trypanosome cell cycle.

PMID- 18048339
TI  - Redirection of cutaneous sensation from the hand to the chest skin of human
      amputees with targeted reinnervation.
AB  - Amputees cannot feel what they touch with their artificial hands, which severely
      limits usefulness of those hands. We have developed a technique that transfers
      remaining arm nerves to residual chest muscles after an amputation. This
      technique allows some sensory nerves from the amputated limb to reinnervate
      overlying chest skin. When this reinnervated skin is touched, the amputees
      perceive that they are being touched on their missing limb. We found that touch
      thresholds of the reinnervated chest skin fall within near-normal ranges,
      indicating the regeneration of large-fiber afferents. The perceptual identity of
      the limb and chest was maintained separately even though they shared a common
      skin surface. A cutaneous expression of proprioception also occurred in one
      reinnervated individual. Experiments with peltier temperature probes and surface
      electrical stimulation of the reinnervated skin indicate the regeneration of
      small diameter temperature and pain afferents. The perception of an amputated
      limb arising from stimulation of reinnervated chest skin may allow useful sensory
      feedback from prosthetic devices and provides insight into the mechanisms of
      neural plasticity and peripheral regeneration in humans.

PMID- 18048340
TI  - Dynamic interplay between nitration and phosphorylation of tubulin cofactor B in
      the control of microtubule dynamics.
AB  - Tubulin cofactor B (TCoB) plays an important role in microtubule dynamics by
      facilitating the dimerization of alpha- and beta-tubulin. Recent evidence
      suggests that p21-activated kinase 1 (Pak1), a major signaling nodule in
      eukaryotic cells, phosphorylates TCoB on Ser-65 and Ser-128 and plays an
      essential role in microtubule regrowth. However, to date, no upstream signaling
      molecules have been identified to antagonize the functions of TCoB, which might
      help in maintaining the equilibrium of microtubules. Here, we discovered that
      TCoB is efficiently nitrated, mainly on Tyr-64 and Tyr-98, and nitrated-TCoB
      attenuates the synthesis of new microtubules. In addition, we found that
      nitration of TCoB antagonizes signaling-dependent phosphorylation of TCoB,
      whereas optimal nitration of TCoB requires the presence of functional Pak1
      phosphorylation sites, thus providing a feedback mechanism to regulate
      phosphorylation-dependent MT regrowth. Together these findings identified TCoB as
      the third cytoskeleton protein to be nitrated and suggest a previously
      undescribed mechanism, whereby growth factor signaling may coordinately integrate
      nitric oxide signaling in the regulation of microtubule dynamics.

PMID- 18048341
TI  - Construction of effective free energy landscape from single-molecule time series.
AB  - A scheme for extracting an effective free energy landscape from single-molecule
      time series is presented. This procedure uniquely identifies a non-Gaussian
      distribution of the observable associated with each local equilibrium state
      (LES). Both the number of LESs and the shape of the non-Gaussian distributions
      depend on the time scale of observation. By assessing how often the system visits
      and resides in a chosen LES and escapes from one LES to another (with checking
      whether the local detailed balance is satisfied), our scheme naturally leads to
      an effective free energy landscape whose topography depends on in which time
      scale the system experiences the underlying landscape. For example, two
      metastable states are unified as one if the time scale of observation is longer
      than the escape time scale for which the system can visit mutually these two
      states. As an illustrative example, we present the application of extracting the
      effective free energy landscapes from time series of the end-to-end distance of a
      three-color, 46-bead model protein. It indicates that the time scales to attain
      the local equilibrium tend to be longer in the unfolded state than those in the
      compact collapsed state.

PMID- 18048342
TI  - Regulation of spine morphology and spine density by NMDA receptor signaling in
      vivo.
AB  - Dendritic spines are the major sites of excitatory synaptic transmission in the
      CNS, and their size and density influence the functioning of neuronal circuits.
      Here we report that NMDA receptor signaling plays a critical role in regulating
      spine size and density in the developing cortex. Genetic deletion of the NR1
      subunit of the NMDA receptor in the cortex leads to a decrease in spine density
      and an increase in spine head size in cortical layer 2/3 pyramidal neurons. This
      process is accompanied by an increase in the presynaptic axon bouton volume and
      the postsynaptic density area, as well as an increase in the miniature excitatory
      postsynaptic current amplitude and frequency. These observations indicate that
      NMDA receptors regulate synapse structure and function in the developing cortex.

PMID- 18048343
TI  - Global climate change, war, and population decline in recent human history.
AB  - Although scientists have warned of possible social perils resulting from climate
      change, the impacts of long-term climate change on social unrest and population
      collapse have not been quantitatively investigated. In this study, high
      resolution paleo-climatic data have been used to explore at a macroscale the
      effects of climate change on the outbreak of war and population decline in the
      preindustrial era. We show that long-term fluctuations of war frequency and
      population changes followed the cycles of temperature change. Further analyses
      show that cooling impeded agricultural production, which brought about a series
      of serious social problems, including price inflation, then successively war
      outbreak, famine, and population decline successively. The findings suggest that
      worldwide and synchronistic war-peace, population, and price cycles in recent
      centuries have been driven mainly by long-term climate change. The findings also
      imply that social mechanisms that might mitigate the impact of climate change
      were not significantly effective during the study period. Climate change may thus
      have played a more important role and imposed a wider ranging effect on human
      civilization than has so far been suggested. Findings of this research may lend
      an additional dimension to the classic concepts of Malthusianism and Darwinism.

PMID- 18048344
TI  - JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer.
AB  - Histone methylation is a dynamic process that participates in a diverse array of
      cellular processes and has been found to associate with cancer. Recently, several
      histone demethylases have been identified that catalyze the removal of
      methylation from histone H3 lysine residues. Through bioinformatic and
      biochemical analysis, we identified JARID1B as a H3K4 demethylase. Overexpression
      of JARID1B resulted in loss of tri-, di-, and monomethyl H3K4 but did not affect
      other histone lysine methylations. In vitro biochemical experiments demonstrated
      that JARID1B directly catalyzes the demethylation. The enzymatic activity
      requires the JmjC domain and uses Fe(II) and alpha-ketoglutarate as cofactors.
      Furthermore, we found that JARID1B is up-regulated in prostate cancer tissues,
      compared with benign prostate samples. We also demonstrated that JARID1B
      associates with androgen receptor and regulates its transcriptional activity.
      Thus, we identified JARID1B as a demethylase capable of removing three methyl
      groups from histone H3 lysine 4 and up-regulated in prostate cancer.

PMID- 18048345
TI  - Gravitational dynamos and the low-frequency geomagnetic secular variation.
AB  - Self-sustaining numerical dynamos are used to infer the sources of low-frequency
      secular variation of the geomagnetic field. Gravitational dynamo models powered
      by compositional convection in an electrically conducting, rotating fluid shell
      exhibit several regimes of magnetic field behavior with an increasing Rayleigh
      number of the convection, including nearly steady dipoles, chaotic nonreversing
      dipoles, and chaotic reversing dipoles. The time average dipole strength and
      dipolarity of the magnetic field decrease, whereas the dipole variability,
      average dipole tilt angle, and frequency of polarity reversals increase with
      Rayleigh number. Chaotic gravitational dynamos have large-amplitude dipole
      secular variation with maximum power at frequencies corresponding to a few cycles
      per million years on Earth. Their external magnetic field structure, dipole
      statistics, low-frequency power spectra, and polarity reversal frequency are
      comparable to the geomagnetic field. The magnetic variability is driven by the
      Lorentz force and is characterized by an inverse correlation between dynamo
      magnetic and kinetic energy fluctuations. A constant energy dissipation theory
      accounts for this inverse energy correlation, which is shown to produce
      conditions favorable for dipole drift, polarity reversals, and excursions.

PMID- 18048346
TI  - NIX is required for programmed mitochondrial clearance during reticulocyte
      maturation.
AB  - The regulated clearance of mitochondria is a well recognized but poorly
      understood aspect of cellular homeostasis, and defects in this process have been
      linked to aging, degenerative diseases, and cancer. Mitochondria are recycled
      through an autophagy-related process, and reticulocytes, which completely
      eliminate their mitochondria during maturation, provide a physiological model to
      study this phenomenon. Here, we show that mitochondrial clearance in
      reticulocytes requires the BCL2-related protein NIX (BNIP3L). Mitochondrial
      clearance does not require BAX, BAK, BCL-X(L), BIM, or PUMA, indicating that NIX
      does not function through established proapoptotic pathways. Similarly, NIX is
      not required for the induction of autophagy during terminal erythroid
      differentiation. NIX is required for the selective elimination of mitochondria,
      however, because mitochondrial clearance, in the absence of NIX, is arrested at
      the stage of mitochondrial incorporation into autophagosomes and autophagosome
      maturation. These results yield insight into the mechanism of mitochondrial
      clearance in higher eukaryotes. Furthermore, they show a BAX- and BAK-independent
      role for a BCL2-related protein in development.

PMID- 18048347
TI  - Ancient jades map 3,000 years of prehistoric exchange in Southeast Asia.
AB  - We have used electron probe microanalysis to examine Southeast Asian nephrite
      (jade) artifacts, many archeologically excavated, dating from 3000 B.C. through
      the first millennium A.D. The research has revealed the existence of one of the
      most extensive sea-based trade networks of a single geological material in the
      prehistoric world. Green nephrite from a source in eastern Taiwan was used to
      make two very specific forms of ear pendant that were distributed, between 500
      B.C. and 500 A.D., through the Philippines, East Malaysia, southern Vietnam, and
      peninsular Thailand, forming a 3,000-km-diameter halo around the southern and
      eastern coastlines of the South China Sea. Other Taiwan nephrite artifacts,
      especially beads and bracelets, were distributed earlier during Neolithic times
      throughout Taiwan and from Taiwan into the Philippines.

PMID- 18048348
TI  - The spectrin cytoskeleton influences the surface expression and activation of
      human transient receptor potential channel 4 channels.
AB  - Despite over a decade of research, only recently have the mechanisms governing
      transient receptor potential channel (TRPC) channel function begun to emerge,
      with an essential role for accessory proteins in this process. We previously
      identified a tyrosine phosphorylation event as critical in the plasma membrane
      translocation and activation of hTRPC4 channels following epidermal growth factor
      (EGF) receptor activation. To further characterize the signaling events
      underlying this process, a yeast-two hybrid screen was performed on the C
      terminus of hTRPC4. The intracellular C-terminal region from proline 686 to
      leucine 977 was used to screen a human brain cDNA library. Two members of the
      spectrin family, alphaII- and betaV-spectrin, were identified as binding
      partners. The interaction of hTRPC4 with alphaII-spectrin and betaV-spectrin was
      confirmed by glutathione S-transferase pulldown and co-immunoprecipitation
      experiments. Deletion analysis identified amino acids 730-758 of hTRPC4 as
      critical for the interaction with this region located within a coiled-coil
      domain, juxtaposing the Ca(2+)/calmodulin- and IP(3)R-binding region (CIRB
      domain). This region is deleted in the proposed deltahTRPC4 splice variant form,
      which failed to undergo both EGF-induced membrane insertion and activation,
      providing a genetic mechanism for regulating channel activity. We also
      demonstrate that the exocytotic insertion and activation of hTRPC4 following EGF
      application is accompanied by dissociation from alphaII-spectrin. Furthermore,
      depletion of alphaII-spectrin by small interference RNA reduces the basal surface
      expression of alphahTRPC4 and prevents the enhanced membrane insertion in
      response to EGF application. Importantly, depletion of alphaII-spectrin did not
      affect the expression of the delta variant. Taken together, these results
      demonstrate that a direct interaction between hTRPC4 and the spectrin
      cytoskeleton is involved in the regulation of hTRPC4 surface expression and
      activation.

PMID- 18048349
TI  - Roles of functional and structural domains of hepatocyte growth factor activator
      inhibitor type 1 in the inhibition of matriptase.
AB  - Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-bound,
      Kunitz-type serine protease inhibitor. HAI-1 inhibits serine proteases that have
      potent pro-hepatocyte growth factor-converting activity, such as the membrane
      type serine protease, matriptase. HAI-1 comprises an N-terminal domain, followed
      by an internal domain, first protease inhibitory domain (Kunitz domain I), low
      density lipoprotein receptor A module (LDLRA) domain, and a second Kunitz domain
      (Kunitz domain II) in the extracellular region. Our aim was to assess the roles
      of these domains in the inhibition of matriptase. Soluble forms of recombinant
      rat HAI-1 mutants made up with various combinations of domains were produced, and
      their inhibitory activities toward the hydrolysis of a chromogenic substrate were
      analyzed using a soluble recombinant rat matriptase. Kunitz domain I exhibited
      inhibitory activity against matriptase, but Kunitz domain II did not. The N
      terminal domain and Kunitz domain II decreased the association rate between
      Kunitz domain I and matriptase, whereas the internal domain increased this rate.
      The LDLRA domain suppressed the dissociation of the Kunitz domain I-matriptase
      complex. Surprisingly, an HAI-1 mutant lacking the N-terminal domain and Kunitz
      domain II showed an inhibitor constant of 1.6 pm, and the inhibitory activity was
      400 times higher in this HAI-1 mutant than in the mutant with all domains. These
      findings, together with the known occurrence of an HAI-1 species lacking the N
      terminal domain and Kunitz domain II in vivo, suggest that the domain structure
      of HAI-1 is organized in a way that allows HAI-1 to flexibly control matriptase
      activity.

PMID- 18048350
TI  - A short motif in Kir6.1 consisting of four phosphorylation repeats underlies the
      vascular KATP channel inhibition by protein kinase C.
AB  - Vascular ATP-sensitive K(+) channels are inhibited by multiple vasoconstricting
      hormones via the protein kinase C (PKC) pathway. However, the molecular
      substrates for PKC phosphorylation remain unknown. To identify the PKC sites,
      Kir6.1/SUR2B and Kir6.2/SUR2B were expressed in HEK293 cells. Following channel
      activation by pinacidil, the catalytic fragment of PKC inhibited the Kir6.1/SUR2B
      currents but not the Kir6.2/SUR2B currents. Phorbol 12-myristate 13-acetate (a
      PKC activator) had similar effects. Using Kir6.1-Kir6.2 chimeras, two critical
      protein domains for the PKC-dependent channel inhibition were identified. The
      proximal N terminus of Kir6.1 was necessary for channel inhibition. Because there
      was no PKC phosphorylation site in the N-terminal region, our results suggest its
      potential involvement in channel gating. The distal C terminus of Kir6.1 was
      crucial where there are several consensus PKC sites. Mutation of Ser-354, Ser
      379, Ser-385, Ser-391, or Ser-397 to nonphosphorylatable alanine reduced PKC
      inhibition moderately but significantly. Combined mutations of these residues had
      greater effects. The channel inhibition was almost completely abolished when 5 of
      them were jointly mutated. In vitro phosphorylation assay showed that 4 of the
      serine residues were necessary for the PKC-dependent (32)P incorporation into the
      distal C-terminal peptides. Thus, a motif containing four phosphorylation repeats
      is identified in the Kir6.1 subunit underlying the PKC-dependent inhibition of
      the Kir6.1/SUR2B channel. The presence of the phosphorylation motif in Kir6.1,
      but not in its close relative Kir6.2, suggests that the vascular K(ATP) channel
      may have undergone evolutionary optimization, allowing it to be regulated by a
      variety of vasoconstricting hormones and neurotransmitters.

PMID- 18048351
TI  - On the role of the first transmembrane domain in cation permeability and flux of
      the ATP-gated P2X2 receptor.
AB  - P2X receptors are a family of seven ligand-gated ion channels (P2X1-P2X7) that
      open in the presence of ATP. We used alanine-scanning mutagenesis and patch clamp
      photometry to study the role of the first transmembrane domain of the rat P2X2
      receptor in cation permeability and flux. Three alanine-substituted mutants did
      not respond to ATP, and 19 of the 22 functional receptors resembled the wild-type
      receptor with regard to the fraction of the total ATP-gated current carried by
      calcium or the permeability of calcium relative to cesium. The remaining three
      mutants showed modest changes in calcium dynamics. Two of these occurred at sites
      (Gly30 and Phe44) that are unlikely to interact with permeating cations in a
      meaningful way. The third was a conserved tyrosine (Tyr43) that may form an inter
      pore binding site for calcium. The data suggest that, with the possible exception
      of Tyr43, the first transmembrane domain contributes little to the permeation
      properties of the P2X2 receptor.

PMID- 18048352
TI  - Gene expression signatures of cAMP/protein kinase A (PKA)-promoted, mitochondrial
      dependent apoptosis. Comparative analysis of wild-type and cAMP-deathless S49
      lymphoma cells.
AB  - The second messenger cAMP acts via protein kinase A (PKA) to induce apoptosis by
      mechanisms that are poorly understood. Here, we assessed a role for mitochondria
      and analyzed gene expression in cAMP/PKA-promoted apoptosis by comparing wild
      type (WT) S49 lymphoma cells and the S49 variant, D(-) (cAMP-deathless), which
      lacks cAMP-promoted apoptosis but has wild-type levels of PKA activity and cAMP
      promoted G(1) growth arrest. Treatment of WT, but not D(-), S49 cells with 8-CPT
      cAMP (8-(4-chlorophenylthio)-adenosine-3':5'-cyclic monophosphate) for 24 h
      induced loss of mitochondrial membrane potential, mitochondrial release of
      cytochrome c and SMAC, and increase in caspase-3 activity. Gene expression
      analysis (using Affymetrix 430 2.0 arrays) revealed that WT and D(-) cells
      incubated with 8-CPT-cAMP have similar, but non-identical, extents of cAMP
      regulated gene expression at 2 h (approximately 800 transcripts) and 6 h
      (approximately 1000 transcripts) (|Fold| > 2, p < 0.06); by contrast, at 24 h,
      approximately 2500 and approximately 1100 transcripts were changed in WT and D(-)
      cells, respectively. Using an approach that combined regression analysis,
      clustering, and functional annotation to identify transcripts that showed
      differential expression between WT and D(-) cells, we found differences in cAMP
      mediated regulation of mRNAs involved in transcriptional repression, apoptosis,
      the cell cycle, RNA splicing, Golgi, and lysosomes. The two cell lines differed
      in cAMP-response element-binding protein (CREB) phosphorylation and expression of
      the transcriptional inhibitor ICER (inducible cAMP early repressor) and in cAMP
      regulated expression of genes in the inhibitor of apoptosis (IAP) and Bcl
      families. The findings indicate that cAMP/PKA-promoted apoptosis of lymphoid
      cells occurs via mitochondrial-mediated events and imply that such apoptosis
      involves gene networks in multiple biochemical pathways.

PMID- 18048353
TI  - A necessary and sufficient determinant for protein-selective glycosylation in
      vivo.
AB  - A limited number of glycoproteins including luteinizing hormone and carbonic
      anhydrase-VI (CA6) bear N-linked oligosaccharides that are modified with beta1,4
      linked N-acetylgalactosamine (GalNAc). The selective addition of GalNAc to these
      glycoproteins requires that the beta1,4-N-acetylgalactosaminyltransferase
      (betaGT) recognize both the oligosaccharide acceptor and a peptide recognition
      determinant on the substrate glycoprotein. We report here that two recently
      cloned betaGTs, betaGT3 and betaGT4, that are able to transfer GalNAc to GlcNAc
      in beta1,4-linkage display the necessary glycoprotein specificity in vivo. Both
      betaGTs transfer GalNAc to N-linked oligosaccharides on the luteinizing hormone
      alpha subunit and CA6 but not to those on transferrin (Trf). A single peptide
      recognition determinant encoded in the carboxyl-terminal 19-amino acid sequence
      of bovine CA6 mediates transfer of GalNAc to each of its two N-linked
      oligosaccharides. The addition of this 19-amino acid sequence to the carboxyl
      terminus of Trf confers full acceptor activity onto Trf for both betaGT3 and
      betaGT4 in vivo. The complete 19-amino acid sequence is required for optimal
      GalNAc addition in vivo, indicating that the peptide sequence is both necessary
      and sufficient for recognition by betaGT3 and betaGT4.

PMID- 18048354
TI  - Structure of the mature ectodomain of the human receptor-type protein-tyrosine
      phosphatase IA-2.
AB  - IA-2 (insulinoma-associated protein 2) is a protein-tyrosine phosphatase receptor
      located in secretory granules of neuroendocrine cells. Initially, it attracted
      attention due to its involvement in the autoimmune response associated to
      diabetes. Later it was found that upon exocytosis, the cytoplasmic domain of IA-2
      is cleaved and relocated to the nucleus, where it enhances the transcription of
      the insulin gene. A concerted functioning of the whole receptor is to be
      expected. However, very little is known about the structure and function of the
      transmembrane and extracellular domains of IA-2. To address this issue, we solved
      the x-ray structure of the mature ectodomain of IA-2 (meIA-2) to 1.30A
      resolution. The fold of meIA-2 is related to the SEA (sea urchin sperm protein,
      enterokinase, agrin)) domains of mucins, suggesting its participation in adhesive
      contacts to the extracellular matrix and providing clues on how this kind of
      molecule may associate and form homo- and heterodimers. Moreover, we discovered
      that meIA-2 is self-proteolyzed in vitro by reactive oxygen species, suggesting
      the possibility of a new shedding mechanism that might be significant in normal
      function or pathological processes. Knowledge of meIA-2 structure should
      facilitate the search of its possible ligands and molecular interactions.

PMID- 18048355
TI  - PKD1, PKD2, and their substrate Kidins220 regulate neurotensin secretion in the
      BON human endocrine cell line.
AB  - Neurotensin (NT) is a gut peptide that plays an important role in
      gastrointestinal secretion, motility, and growth as well as the proliferation of
      NT receptor-positive cancers. Protein kinase D (PKD) family members (PKD1, 2, and
      3) have been identified as important regulators of secretory transport at the
      trans-Golgi network. Previously, we showed that PKD1 contributes to stimulated NT
      secretion; however, the mechanisms are not entirely clear. Here, we show that
      Kidins220, which is a substrate of PKD proteins in neuroendocrine cells, is
      localized in the ends of the processes of BON cells, similar to the expression
      pattern of NT vesicles, and translocates to the membrane and large vesicle-like
      structures formed in response to phorbol 12-myristate 13-acetate treatment. The
      short hairpin RNA targeting Kidins220 inhibits NT secretion in parental BON cells
      or BON cells stably expressing the gastrin-releasing peptide receptor treated
      with either phorbol 12-myristate 13-acetate or bombesin, respectively.
      Furthermore, we demonstrate that endogenous PKD1, PKD2, and Kidins220 co-exist
      with NT-containing vesicles. Overexpression of the kinase-dead PKD1 abrogates
      Kidins220 expression and NT vesicle formation. Our data establish a physiological
      link between the PKD/Kidins220 pathway and NT-containing vesicles and suggest the
      role of this pathway in the regulation of hormone secretion. Because NT is an
      important gut hormone that affects secretion, inflammation, and both normal and
      tumor cell growth, our findings identify a novel signaling pathway that may be
      amenable to drug targeting for clinical applications.

PMID- 18048356
TI  - The TbMTr1 spliced leader RNA cap 1 2'-O-ribose methyltransferase from
      Trypanosoma brucei acts with substrate specificity.
AB  - In metazoa cap 1 (m(7)GpppNmp-RNA) is linked to higher levels of translation;
      however, the enzyme responsible remains unidentified. We have validated the first
      eukaryotic encoded cap 1 2'-O-ribose methyltransferase, TbMTr1, a member of a
      conserved family that modifies the first transcribed nucleotide of spliced leader
      and U1 small nuclear RNAs in the kinetoplastid protozoan Trypanosoma brucei. In
      addition to cap 0 (m(7)GpppNp-RNA), mRNA in these parasites has ribose
      methylations on the first four nucleotides with base methylations on the first
      and fourth (m(7)Gpppm(6,6)AmpAmpCmpm(3)Ump-SL RNA) conveyed via trans-splicing of
      a universal spliced leader. The function of this cap 4 is unclear. Spliced leader
      is the majority RNA polymerase II transcript; the RNA polymerase III-transcribed
      U1 small nuclear RNA has the same first four nucleotides as spliced leader, but
      it receives an m(2,2,7)G cap with hypermethylation at position one only
      (m(2,2,7)Gpppm(6,6)AmpApCpUp-U1 snRNA). Here we examine the biochemical
      properties of recombinant TbMTr1. Active over a pH range of 6.0 to 9.5, TbMTr1 is
      sensitive to Mg(2+). Positions Lys(95)-Asp(204)-Lys(259)-Glu(285) constitute the
      conserved catalytic core. A guanosine cap on RNA independent of its N(7)
      methylation status is required for substrate recognition, but an m(2,2,7G)-cap is
      not recognized. TbMTr1 favors the spliced leader 5' sequence, as reflected by a
      preference for A at position 1 and modulation of activity for substrates with
      base changes at positions 2 and 3. With similarities to human cap 1
      methyltransferase activity, TbMTr1 is an excellent model for higher eukaryotic
      cap 1 methyltransferases and the consequences of cap 1 modification.

PMID- 18048357
TI  - The alpha1a-adrenergic receptor occupies membrane rafts with its G protein
      effectors but internalizes via clathrin-coated pits.
AB  - The alpha(1a)-adrenergic receptor (alpha(1a)AR) occupies intracellular and plasma
      membranes in both native and heterologous expression systems. Based on multiple
      independent lines of evidence, we demonstrate the alpha(1a)AR at the cell surface
      occupies membrane rafts but exits from rafts following stimulation. In non
      detergent raft preparations, basal alpha(1a)AR is present in low density membrane
      rafts and colocalizes with its G protein effectors on density gradients. Raft
      disruption by cholesterol depletion with methyl-beta-cyclodextrin eliminates
      these light rafts. To confirm the presence of the alpha(1a)AR in plasma membrane
      rafts, fluorescence resonance energy transfer measurements were used to
      demonstrate colocalization of surface receptor and the raft marker, cholera toxin
      B. This colocalization was largely lost following alpha(1a)AR stimulation with
      phenylephrine. Similarly, receptor stimulation causes exit of the alpha(1a)AR
      from light rafts within 3-10 min in contrast to the G proteins, which largely
      remain in light rafts. Importantly, this delayed exit of the alpha(1a)AR suggests
      acute receptor signaling and desensitization occur entirely within rafts.
      Interestingly, both confocal analysis and measurement of surface alpha(1a)AR
      levels indicate modest receptor internalization during the 10 min following
      stimulation, suggesting most of the receptor has entered non-raft plasma
      membrane. Nevertheless, activation does increase the rate of receptor
      internalization as does disruption of rafts with methyl-beta-cyclodextrin,
      suggesting raft exit enables internalization. Confocal analysis of surface
      labeled hemagglutinin-alpha(1a)AR reveals that basal and stimulated receptor
      occupies clathrin pits in fixed cells consistent with previous indirect evidence.
      The evidence presented here strongly suggests the alpha(1a)AR is a lipid raft
      protein under basal conditions and implies agonist-mediated signaling occurs from
      rafts.

PMID- 18048358
TI  - Extracellular signal-regulated kinase regulation of tumor necrosis factor-alpha
      mRNA nucleocytoplasmic transport requires TAP-NxT1 binding and the AU-rich
      element.
AB  - Tumor necrosis factor-alpha (TNF-alpha) production is regulated by
      transcriptional and posttranscriptional mechanisms. Lipopolysaccharide activates
      the NFkappaB pathway increasing TNF-alpha transcription. Lipopolysaccharide also
      activates the mitogen-activated protein kinase pathways, resulting in
      stabilization and enhanced translation of the TNF-alpha message. In addition,
      nuclear export of the TNF-alpha mRNA is a posttranscriptionally regulated process
      involving the Tpl2-ERK pathway and requiring the presence of the TNF-alpha AU
      rich element (ARE). We demonstrate that nuclear export of the TNF-alpha message
      requires not only the TNF-alpha ARE but also the interaction of the proteins TAP
      and NxT1, both of which are involved in nucleocytoplasmic transport of mRNA.
      Through the use of dominant negative ERK1 and ERK2, we establish that control of
      TNF-alpha mRNA nuclear export operates specifically through ERK1. Finally, we
      examined the role of two established TNF-alpha ARE-binding proteins, HuR and
      tristetraprolin, that shuttle between the nucleus and cytoplasm. These data
      demonstrate that neither tristetraprolin nor HuR is required for TNF-alpha mRNA
      export. It is unclear at this time if ARE-binding protein(s) directly interact
      with the TAP-NxT1 complex, if each complex is independently targeted by ERK1, or
      if only one complex is targeted.

PMID- 18048359
TI  - Regulatory effects of mammalian target of rapamycin-mediated signals in the
      generation of arsenic trioxide responses.
AB  - Arsenic trioxide (As(2)O(3)) is a potent inducer of apoptosis of leukemic cells
      in vitro and in vivo, but the mechanisms that mediate such effects are not well
      understood. We provide evidence that the Akt kinase is phosphorylated/activated
      during treatment of leukemia cells with As(2)O(3), to regulate downstream
      engagement of mammalian target of rapamycin (mTOR) and its effectors. Using cells
      with targeted disruption of both the Akt1 and Akt2 genes, we found that induction
      of arsenic trioxide-dependent apoptosis is strongly enhanced in the absence of
      these kinases, suggesting that Akt1/Akt2 are activated in a negative feedback
      regulatory manner, to control generation of As(2)O(3) responses. Consistent with
      this, As(2)O(3)-dependent pro-apoptotic effects are enhanced in double knock-out
      cells for both isoforms of the p70 S6 kinase (S6k1/S6k2), a downstream effector
      of Akt and mTOR. On the other hand, As(2)O(3)-dependent induction of apoptosis is
      diminished in cells with targeted disruption of TSC2, a negative upstream
      effector of mTOR. In studies using primary hematopoietic progenitors from
      patients with acute myeloid leukemia, we found that pharmacological inhibition of
      mTOR enhances the suppressive effects of arsenic trioxide on leukemic progenitor
      colony formation. Moreover, short interfering RNA-mediated inhibition of
      expression of the negative downstream effector, translational repressor 4E-BP1,
      partially reverses the effects of As(2)O(3). Altogether, these data provide
      evidence for a key regulatory role of the Akt/mTOR pathway in the generation of
      the effects of As(2)O(3), and suggest that targeting this signaling cascade may
      provide a novel therapeutic approach to enhance the anti-leukemic properties of
      As(2)O(3).

PMID- 18048361
TI  - Structural basis for the lower affinity of the insulin-like growth factors for
      the insulin receptor.
AB  - Insulin and the insulin-like growth factors (IGFs) bind with high affinity to
      their cognate receptor and with lower affinity to the noncognate receptor. The
      major structural difference between insulin and the IGFs is that the IGFs are
      single chain polypeptides containing A-, B-, C-, and D-domains, whereas the
      insulin molecule contains separate A- and B-chains. The C-domain of IGF-I is
      critical for high affinity binding to the insulin-like growth factor I receptor,
      and lack of a C-domain largely explains the low affinity of insulin for the
      insulin-like growth factor I receptor. It is less clear why the IGFs have lower
      affinity for the insulin receptor. In this study, 24 insulin analogues and four
      IGF analogues were expressed and analyzed to explore the role of amino acid
      differences in the A- and B-domains between insulin and the IGFs in binding
      affinity for the insulin receptor. Using the information obtained from single
      substituted analogues, four multiple substituted analogues were produced. A
      "quadruple insulin" analogue ([Phe(A8), Ser(A10), Thr(B5), Gln(B16)]Ins) showed
      affinity as IGF-I for the insulin receptor, and a "sextuple insulin" analogue
      ([Phe(A8), Ser(A10), Thr(A18), Thr(B5), Thr(B14), Gln(B16)]Ins) showed an
      affinity close to that of IGF-II for the insulin receptor, whereas a "quadruple
      IGF-I" analogue ([His(4), Tyr(15), Thr(49), Ile(51)]IGF-I) and a "sextuple IGF
      II" analogue ([His(7), Ala(16), Tyr(18), Thr(48), Ile(50), Asn(58)]IGF-II) showed
      affinities similar to that of insulin for the insulin receptor. The mitogenic
      potency of these analogues correlated well with the binding properties. Thus, a
      small number of A- and B-domain substitutions that map to the IGF surface
      equivalent to the classical binding surface of insulin weaken two hotspots that
      bind to the insulin receptor site 1.

PMID- 18048360
TI  - Thrombin induces tumor invasion through the induction and association of matrix
      metalloproteinase-9 and beta1-integrin on the cell surface.
AB  - The procoagulatory serine protease, thrombin, is known to induce invasion and
      metastasis in various cancers, but the mechanisms by which it promotes
      tumorigenesis are poorly understood. Because the 92-kDa gelatinase (MMP-9) is a
      known mediator of tumor cell invasion, we sought to determine whether and how
      thrombin regulates MMP-9. The thrombin receptor, PAR-1, and MMP-9 are expressed
      in osteosarcomas, as determined by immunohistochemistry. Stimulation of U2-OS
      osteosarcoma cells with thrombin and a thrombin receptor-activating peptide
      induced pro-MMP-9 secretion as well as cell surface-associated pro-MMP-9
      expression and proteolytic activity. This was paralleled by an increase in MMP-9
      mRNA and MMP-9 promoter activity. Thrombin-induced invasion of U2-OS cells
      through Matrigel was mediated by the phosphatidylinositol 3-kinase signaling
      pathway and could be inhibited with an MMP-9 antibody. The stimulation of MMP-9
      by thrombin was paralleled by an increase in beta1-integrin mRNA and beta1
      integrin expression on the cell surface, which was also mediated by
      phosphatidylinositol 3-kinase and was required for invasion. Thrombin activation
      induced and co-localized both beta1-integrin and pro-MMP-9 on the cell membrane,
      as evidenced by co-immunoprecipitation, confocal microscopy, and a protein
      binding assay. The thrombin-mediated association of these two proteins, as well
      as thrombin-mediated invasion of U2-OS cells, could be blocked with a cyclic
      peptide and with an antibody preventing binding of the MMP-9 hemopexin domain to
      beta1-integrin. These results suggest that thrombin induces expression and
      association of beta1-integrin with MMP-9 and that the cell surface localization
      of the protease by the integrin promotes tumor cell invasion.

PMID- 18048363
TI  - Evidence that sprouty 2 is necessary for sarcoma formation by H-Ras oncogene
      transformed human fibroblasts.
AB  - Sprouty 2 (Spry2) acts as an inhibitor of receptor tyrosine kinase signaling in
      various cellular contexts. Interestingly, Spry2 also prevents the c-Cbl-induced
      degradation of epidermal growth factor receptor (EGFR). We compared human
      fibroblasts malignantly transformed by overexpression of H-Ras(V12) oncogene to
      their nontransformed parental cells and found that the malignant cells express a
      high level of Spry2. These cells also exhibited an increase in the level of EGFR
      compared with their precursor cells. We found that intact EGFR was required if H
      Ras-transformed cells were to grow in the absence of exogenous growth factors or
      form large colonies in agarose. When we decreased expression of Spry2, using a
      Spry2-specific shRNA, the H-Ras(V12)-transformed fibroblasts could no longer form
      large colonies in agarose, grow in reduced levels of serum, or form tumors in
      athymic mice. The level of active H-Ras in these cells remained unaltered. A
      similar, but less pronounced, effect in tumor formation was observed when Spry2
      was down-regulated in human patient-derived fibrosarcoma cell lines. In H-Ras
      transformed cells Spry2 sustained the level and the downstream signaling activity
      of EGFR. In the parental, non-H-Ras-transformed fibroblasts, expression of Spry2
      resulted in the inhibition of H-Ras and ERK activation, suggesting that the
      positive effect of Spry2 in tumor formation is specific to H-Ras transformation.
      Co-immunoprecipitation studies with H-Ras-transformed cells revealed that Spry2
      and H-Ras interact and that H-Ras interacts with Spry2-binding partners, c-Cbl
      and CIN85, in a Spry2-dependent manner. These data show that Spry2 plays a
      critical role in the ability of H-Ras-transformed cells to form tumors in athymic
      mice.

PMID- 18048362
TI  - Signaling by the cysteinyl-leukotriene receptor 2. Involvement in chemokine gene
      transcription.
AB  - Cysteinyl-leukotrienes are involved in inflammation and act on at least two G
      protein-coupled receptors, CysLT1 and CysLT2. However, the role of the CysLT2
      receptor as well as its signaling remain poorly understood. Here we show that
      leukotriene (LT)C(4) induced the production of the chemokine interleukin (IL)-8
      in endothelial cells. To further study the signaling cascade involved, HEK293
      cells were stably transfected with CysLT2 and used to study the transcriptional
      regulation of the IL-8 promoter. Stimulation of the cells with increasing
      concentrations of LTC(4) resulted in a time- and concentration-dependent
      induction of IL-8 transcription and protein synthesis. Use of IL-8 promoter
      mutants with substitutions in their NF-kappaB, AP-1, or NF-IL-6 binding elements
      revealed an almost total requirement for NF-kappaB and AP-1 elements, and a
      lesser requirement for the NF-IL-6 element. Overexpression of dominant-negative
      IkappaBalpha prevented the IL-8 transactivation induced by LTC(4). LTC(4)
      stimulation induced NF-kappaB and AP-1 DNA binding, which involved the formation
      of a p50/p65 and a c-JUN.c-FOS complex, respectively. Transfection of the cells
      with a dominant negative (dn) form of PKCepsilon prevented p65 phosphorylation,
      whereas dnPKCdelta prevented AP-1 binding. Moreover, dnPKCdelta, dnPKCepsilon,
      and dnPKCzeta prevented LTC(4)-induced IL-8 transcription in response to LTC(4).
      Our data show for the first time that LTC(4) can act via the CysLT2 receptor to
      transcriptionally activate chemokine production through induction of NF-kappaB
      and AP-1 transcription factors. These findings suggest the potential implication
      of CysLT2 in the inflammatory response through the modulation of chemokine gene
      transcription.

PMID- 18048364
TI  - Endoplasmic reticulum retention and rescue by heteromeric assembly regulate human
      ERG 1a/1b surface channel composition.
AB  - Defects in the trafficking of subunits encoded by the human ether-a-go-go-related
      gene (hERG1) can lead to catastrophic arrhythmias and sudden cardiac death due to
      a reduction in I(Kr)-mediated repolarization. Native I(Kr) channels are composed
      of two alpha subunits, hERG 1a and 1b. In heterologous expression systems, hERG
      1b subunits efficiently produce current only in heteromeric combination with hERG
      1a. We used Western blot analysis and electrophysiological recordings in HEK-293
      cells and Xenopus oocytes to monitor hERG 1b maturation in the secretory pathway
      and to determine the factors regulating surface expression of hERG 1b subunits.
      We found that 1b subunits expressed alone were largely retained in the
      endoplasmic reticulum (ER), thus accounting for the poor functional expression of
      homomeric 1b currents. Association with hERG 1a facilitated 1b ER export and
      surface expression. We show that hERG 1b subunits fail to mature because of an
      "RXR" ER retention signal specific to the 1b N terminus of the human sequence and
      not conserved in other species. Mutating the RXR facilitated maturation and
      functional expression of homomeric hERG 1b channels in a charge-dependent manner.
      Co-expression of the 1b RXR mutants with hERG 1a did not further enhance 1b
      maturation, suggesting that hERG 1a promotes 1b trafficking by overcoming the RXR
      mediated retention. Thus, selective trafficking mechanisms regulate subunit
      composition of surface hERG channels.

PMID- 18048365
TI  - B-cell receptor activation induces BIC/miR-155 expression through a conserved AP
      1 element.
AB  - microRNA-155 is an oncogenic microRNA that has been shown to be critical for B
      cell maturation and immunoglobulin production in response to antigen. In line
      with its function in B-cell activation, miR-155, and its primary transcript, B
      cell integration cluster (BIC), is induced by B-cell receptor (BCR) cross
      linking. Using pharmacological inhibitors in the human B-cell line, Ramos, we
      show that activation of BIC and miR-155 expression by BCR signaling occurs
      through the extracellular signaling-regulated kinase (ERK) and c-Jun N-terminal
      kinase (JNK) pathways but not the p38 pathway. BCR activation results in the
      induction of c-Fos, FosB, and JunB, and expression of these are suppressed by ERK
      and JNK inhibitors. Reporter analysis established a key role for a conserved AP-1
      site approximately 40 bp upstream from the site of initiation but not an upstream
      NF-kappaB site or a putative c-Ets located at the site of initiation. Lastly,
      chromatin immunoprecipitation analysis demonstrated the recruitment of FosB and
      JunB to the miR-155 promoter following BCR activation. These results identify key
      determinants of BCR-mediated signaling that lead to the induction of BIC/miR-155.

PMID- 18048366
TI  - Modulation of yeast Sln1 kinase activity by the CCW12 cell wall protein.
AB  - The yeast Sln1p sensor kinase is best known as an osmosensor involved in the
      regulation of the hyperosmolarity glycerol mitogen-activated protein kinase
      cascade. Down-regulation of Sln1 kinase activity occurs under hypertonic
      conditions and leads to phosphorylation of the Hog1p mitogen-activated protein
      kinase and increased osmotic stress-response gene expression. Conditions leading
      to kinase up-regulation include osmotic imbalance caused by glycerol retention in
      the glycerol channel mutant, fps1 (Tao, W., Deschenes, R. J., and Fassler, J. S.
      (1999) J. Biol. Chem. 274, 360-367). The hypothesis that Sln1p kinase activity is
      responsive to turgor was first suggested by the increased Sln1p kinase activity
      in mutants lacking Fps1p in which glycerol accumulation leads to water uptake.
      Also consistent with the turgor hypothesis is the observation that reduced turgor
      caused by treatment of cells with nystatin, a drug that increases membrane
      permeability and causes cell shrinkage, reduced Sln1p kinase activity (Tao, W.,
      Deschenes, R. J., and Fassler, J. S. (1999) J. Biol. Chem. 274, 360-367; Reiser,
      V., Raitt, D. C., and Saito, H. (2003) J. Cell Biol. 161, 1035-1040). The turgor
      hypothesis is revisited here in the context of the identification and
      characterization of the cell wall gene, CCW12, as a determinant of Sln1p
      activity. Results of this analysis suggest that the activity of the plasma
      membrane localized Sln1p is affected by the presence or absence of specific outer
      cell wall proteins and that this effect is independent of turgor.

PMID- 18048367
TI  - Sequences in intron 51 of the von Willebrand factor gene target promoter
      activation to a subset of lung endothelial cells in transgenic mice.
AB  - In vivo analyses of the VWF promoter previously demonstrated that a fragment
      spanning sequences -487 to +247 targets promoter activation to brain vascular
      endothelial cells, whereas a longer fragment including 2182 bp of the 5'-flanking
      sequences, the first exon, and the first intron activated expression in
      endothelial cells of the heart and muscles as well as the brain of transgenic
      mice. These results suggested that additional VWF gene sequences were required
      for expression in other vascular endothelial cells in vivo. We have now
      identified a region within intron 51 of the VWF gene that is DNase I
      hypersensitive (HSS) specifically in non-endothelial cells and interacts with
      endothelial and non-endothelial specific complexes that contain YY1. We
      demonstrate that beta-actin is associated with YY1 specifically in the nucleus of
      non-endothelial cells and is a component of the nuclear protein complexes that
      interact with the DNase I-hypersensitive region. In vitro transfection analyses
      demonstrated that HSS sequences containing this YY1-binding site do not
      significantly affect VWF promoter activity. However, in vivo analyses
      demonstrated that addition of these sequences to the VWF promoter (-487 to +247)
      results in promoter activation in lung and brain vascular endothelial cells.
      These results demonstrate that the HSS sequences in intron 51 of the VWF gene
      contain cis-acting elements that are necessary for the VWF gene transcription in
      a subset of lung endothelial cells in vivo.

PMID- 18048368
TI  - Effects and interactions in an environmentally relevant mixture of
      pharmaceuticals.
AB  - With the goal of assessing the environmental risk of pharmaceuticals, we have
      previously observed that a mixture of 13 different drugs at environmentally
      relevant concentrations had adverse consequences on human and zebra fish cells in
      vitro. Here we aimed to identify both main and interaction effects within the
      same environmentally relevant mixture of pharmaceuticals. We studied in vitro
      cytotoxicity in Escherichia coli, human embryonic HEK293, and estrogen-responsive
      OVCAR3 tumor cells using fractional-factorial experimental design. Our approach
      identified a subset of compounds of primary environmental concern, namely
      atenolol, bezafibrate, ciprofloxacin, and lincomycin, that had statistically
      significant effects on prokaryotic and eukaryotic cells at environmentally
      relevant exposure levels (ng/l). Drugs could interact and behave as
      chemosensitizers, with joint effects representing a statistically significant
      element of mixture toxicity. Effects and interactions were concentration
      dependent, confirming the difficulty of dose extrapolation in mixture toxicity
      data. This study suggests that a thorough investigation of mixture effects can
      direct environmental concerns toward a handful of pharmaceuticals, which may
      represent an actual risk at environmental concentrations. We indicate that risk
      identification may strongly depend on the use of environmentally relevant
      exposure scenarios. Antagonistic-synergistic interactions and dose dependency of
      effects may hamper the modeling and prediction of mixture toxicity with
      pharmaceuticals. Hazard identification for micropollutants depends heavily on
      appropriate study designs, and we indicate the use of in vitro cytotoxicity
      threshold and statistical design of experiments (DOEs) as a valid approach.

PMID- 18048369
TI  - Modeling reading vocabulary learning in deaf children in bilingual education
      programs.
AB  - The acquisition of reading vocabulary is one of the major challenges for deaf
      children in bilingual education programs. Deaf children have to acquire a written
      lexicon that can effectively be used in reading. In this paper, we present a
      developmental model that describes reading vocabulary acquisition of deaf
      children in bilingual education programs. The model is inspired by Jiang's model
      of vocabulary development in a second language (N. Jiang, 2000, 2004a) and the
      hierarchical model of lexical representation and processing in bilinguals (J. F.
      Kroll & E. Stewart, 1988). We argue that lexical development in the written
      language often fossilizes and that many words deaf readers acquire will not reach
      the final stage of lexical development. We argue that this feature is consistent
      with many findings reported in the literature. Finally, we discuss the
      pedagogical implications of the model.

PMID- 18048370
TI  - Experience-induced changes in sugar taste discrimination.
AB  - An apparent plasticity in glucose sensitivity was first noted while studying
      human taste variants, but the experimental design did not rule out regression to
      the mean. Since then, a human taste induction hypothesis that sensitivity for a
      taste stimulus increases with repeated exposure to it has been supported first by
      experience-induced changes in taste identification of monosodium glutamate and,
      subsequently, in sensory detection of glutaraldehyde, as well as in
      psychophysical and functional magnetic resonance imaging responses to novel taste
      stimuli. Yet, whether such plasticity occurs for the highly familiar taste of
      sugar remained unconfirmed. Therefore, we tested the taste induction hypothesis
      for sugar using a counterbalanced design, consisting of 3 pretreatment and 2
      treatment conditions. The effects over time also were followed with an additional
      group of participants. The results showed that 1) experience with fructose
      significantly increases sensitivity for the taste of a sugar, glucose; 2) there
      are no significant differences in the sugar sensitivity between groups of
      randomly assigned participants before treatments; 3) a single session of 5 brief
      tastings of glucose has an effect on glucose sensitivity when tested 11 or 12
      days later; and 4) without continued treatment, the increased sensitivity
      reverses within 33 or 34 days.

PMID- 18048371
TI  - Mechanistic mathematical model for in vivo aroma release during eating of
      semiliquid foods.
AB  - The paper describes a mechanistic mathematical model for aroma release in the
      oropharynx to the nasal cavity during food consumption. The model is based on the
      physiology of the swallowing process and is validated with atmospheric pressure
      chemical ionization coupled with mass spectrometry measurements of aroma
      concentration in the nasal cavity of subjects eating flavored yogurt. The study
      is conducted on 3 aroma compounds representative for strawberry flavor (ethyl
      acetate, ethyl butanoate, and ethyl hexanoate) and 3 panelists. The model
      provides reasonably accurate time predictions of the relative aroma concentration
      in the nasal cavity and is able to simulate successive swallowing events as well
      as imperfect velopharyngeal closure. The most influent parameters are found to be
      the amount of the residual product in the pharynx and its contact area with the
      air flux, the volume of the nasal cavity, the equilibrium air/product partition
      coefficient of the volatile compound, the breath airflow rate, as well as the
      mass transfer coefficient of the aroma compound in the product, and the amount of
      product in the mouth. This work constitutes a first step toward computer-aided
      product formulation by allowing calculation of retronasal aroma intensity as a
      function of transfer and volatility properties of aroma compounds in food
      matrices and anatomophysiological characteristics of consumers.

PMID- 18048372
TI  - Regulation of Rubisco activase and its interaction with Rubisco.
AB  - The large, alpha-isoform of Rubisco activase confers redox regulation of the
      ATP/ADP response of the ATP hydrolysis and Rubisco activation activities of the
      multimeric activase holoenzyme complex. The alpha-isoform has a C-terminal
      extension that contains the redox-sensitive cysteine residues and is
      characterized by a high content of acidic residues. Cross-linking and site
      directed mutagenesis studies of the C-terminal extension that have provided new
      insights into the mechanism of redox regulation are reviewed. Also reviewed are
      new details about the interaction between activase and Rubisco and the likely
      mechanism of 'activation' that resulted from mutagenesis in a 'Sensor 2' domain
      of activase that AAA(+) proteins often use for substrate recognition. Two
      activase residues in this domain were identified that are involved in Rubisco
      recognition. The results directly complement earlier studies that identified
      critical residues for activase recognition in the large subunit of Rubisco.

PMID- 18048373
TI  - Role of ethylene in the protection of tomato plants against soil-borne fungal
      pathogens conferred by an endophytic Fusarium solani strain.
AB  - An endophytic fungal isolate (Fs-K), identified as a Fusarium solani strain, was
      obtained from root tissues of tomato plants grown on a compost which suppressed
      soil and foliar pathogens. Strain Fs-K was able to colonize root tissues and
      subsequently protect plants against the root pathogen Fusarium oxysporum f.sp.
      radicis-lycopersici (FORL), and elicit induced systemic resistance against the
      tomato foliar pathogen Septoria lycopersici. Interestingly, attenuated expression
      of certain pathogenesis-related genes, i.e. PR5 and PR7, was detected in tomato
      roots inoculated with strain Fs-K compared with non-inoculated plants. The
      expression pattern of PR genes was either not affected or aberrant in leaves. A
      genetic approach, using mutant tomato plant lines, was used to determine the role
      of ethylene and jasmonic acid in the plant's response to infection by the soil
      borne pathogen F. oxysporum f.sp. radicis-lycopersici (FORL), in the presence or
      absence of isolate Fs-K. Mutant tomato lines Never ripe (Nr) and epinastic
      (epi1), both impaired in ethylene-mediated plant responses, inoculated with FORL
      are not protected by isolate Fs-K, indicating that the ethylene signalling
      pathway is required for the mode of action used by the endophyte to confer
      resistance. On the contrary, def1 mutants, affected in jasmonate biosynthesis,
      show reduced susceptibility to FORL, in the presence Fs-K, which suggests that
      jasmonic acid is not essential for the mediation of biocontrol activity of
      isolate Fs-K.

PMID- 18048374
TI  - Quantitative trait loci for flowering time and morphological traits in multiple
      populations of Brassica rapa.
AB  - Wide variation for morphological traits exists in Brassica rapa and the genetic
      basis of this morphological variation is largely unknown. Here is a report on
      quantitative trait loci (QTL) analysis of flowering time, seed and pod traits,
      growth-related traits, leaf morphology, and turnip formation in B. rapa using
      multiple populations. The populations resulted from crosses between the following
      accessions: Rapid cycling, Chinese cabbage, Yellow sarson, Pak choi, and a
      Japanese vegetable turnip variety. A total of 27 QTL affecting 20 morphological
      traits were detected, including eight QTL for flowering time, six for seed
      traits, three for growth-related traits and 10 for leaf traits. One major QTL was
      found for turnip formation. Principal component analysis and co-localization of
      QTL indicated that some loci controlling leaf and seed-related traits and those
      for flowering time and turnip formation might be the same. The major flowering
      time QTL detected in all populations on linkage group R02 co-localized with
      BrFLC2. One major QTL, controlling turnip formation, was also mapped at this
      locus. The genes that may underly this QTL and comparative analyses between the
      four populations and with Arabidopsis thaliana are discussed.

PMID- 18048375
TI  - Blood pressure and risk of renal cell carcinoma in the European prospective
      investigation into cancer and nutrition.
AB  - Elevated blood pressure has been implicated as a risk factor for renal cell
      carcinoma (RCC), but prospective studies were confined to men and did not
      consider the effect of antihypertensive medication. The authors examined the
      relation among blood pressure, antihypertensive medication, and RCC in the
      European Prospective Investigation into Cancer and Nutrition (EPIC). Blood
      pressure was measured in 296,638 women and men, recruited in eight European
      countries during 1992-1998, 254,935 of whom provided information on
      antihypertensive medication. During a mean follow-up of 6.2 years, 250 cases of
      RCC were identified. Blood pressure was independently associated with risk of
      RCC. The relative risks for the highest versus the lowest category of systolic
      (>/=160 mmHg vs. <120 mmHg) and diastolic (>/=100 mmHg vs. <80 mmHg) blood
      pressures were 2.48 (95% confidence interval: 1.53, 4.02) and 2.34 (95%
      confidence interval: 1.54, 3.55). Risk estimates did not significantly differ
      according to sex or use of antihypertensive medication. Individuals taking
      antihypertensive drugs were not at a significantly increased risk unless blood
      pressure was poorly controlled. These results support the hypothesis that
      hypertension, rather than its medications, increases the risk of RCC in both
      sexes, while effective blood pressure control may lower the risk.

PMID- 18048376
TI  - Familial patterns of preterm delivery: maternal and fetal contributions.
AB  - Women who deliver preterm (<37 completed weeks' gestation) are at high risk for
      recurrence. This has prompted exploration of candidate genes (both maternal and
      fetal) associated with preterm delivery. Epidemiologists can use recurrence
      patterns of preterm delivery across generations to assess the relative
      contributions of maternal and fetal genes. The authors used data from the Medical
      Birth Registry of Norway (1967-2004) to identify 191,282 mothers and 127,830
      fathers who subsequently had at least one singleton offspring. The authors
      stratified parents according to whether or not they had been born preterm and
      calculated the risk of preterm delivery among their firstborn. Mothers born
      preterm had a relative risk for preterm delivery of 1.54 (95% confidence interval
      (CI): 1.42, 1.67). This association was weaker for fathers born preterm (relative
      risk (RR) = 1.12, 95% CI: 1.01, 1.25). Among early preterm births (<35 weeks),
      the effect became stronger for mothers (RR = 1.85, 95% CI: 1.52, 2.27) and weaker
      for fathers (RR = 1.06, 95% CI: 0.77, 1.44). These data suggest that paternal
      genes have little, if any, effect on preterm delivery risk. This argues against
      major contributions of fetal genes inherited from either parent. The increased
      risk of preterm delivery among mothers born preterm is consistent with heritable
      maternal phenotypes that confer a propensity to deliver preterm.

PMID- 18048377
TI  - Dietary patterns and risk of incident gastric adenocarcinoma.
AB  - Few studies have assessed the relation between dietary patterns and gastric
      adenocarcinoma risk, yet this approach has advantages over single-nutrient
      analysis, including the ability to reflect eating patterns in populations and
      ease of implementing dietary recommendations. The authors evaluated associations
      between dietary patterns, a food index score, and incident gastric cancer risk in
      a Canadian study of 1,169 cases and 2,332 controls (1995-1997). Dietary patterns
      were assessed via factor analysis applied to a food frequency questionnaire. A
      food index score was derived based on risk factors for gastric cancer. A
      multivariable-adjusted prudent dietary pattern was associated with decreased risk
      of gastric cancer in women (odds ratio (OR) = 0.58, 95% confidence interval (CI):
      0.37, 0.92); a Western dietary pattern was associated with increased risk in
      women (OR = 1.86, 95% CI: 1.20, 2.89) and men (OR = 1.44, 95% CI: 1.03, 2.02).
      The food index score was associated with decreased risk among women (OR = 0.40,
      95% CI: 0.27, 0.59) and men (OR = 0.63, 95% CI: 0.45, 0.88). Dietary patterns
      especially characterized by Western features (soft drinks, processed meats,
      refined grains, and sugars) were associated with increased risk of gastric
      adenocarcinoma, whereas dietary patterns characterized by increased consumption
      of fruits, vegetables, and fish were associated with lessened risk.

PMID- 18048378
TI  - Brothers and reduction of the birth weight of later-born siblings.
AB  - It has been speculated whether maternal immune responses against male-specific
      minor histocompatibility (H-Y) antigens affect pregnancies negatively. This study
      explores, on a population level, whether previous births of boys compared with
      girls are associated with a decrease in birth weight of later-born siblings. The
      population was identified in the Danish Birth Registry and consisted of all
      Danish women who gave birth to their first-born singleton from 1980 to 1998. The
      women were followed until 2004, and their subsequent births were recorded. A
      total of 545,839 second- to fourth-born children were identified. The authors
      used linear regression to analyze the association between sex of preceding
      children and birth weight of subsequent siblings. Brothers compared with sisters
      reduced the birth weight of later-born siblings. One or two brothers,
      respectively, reduced the mean birth weight of later-born boys by 29 g (p =
      0.0001) and 38 g (p = 0.0001) and later-born girls by 17 g (p = 0.0001) and 21 g
      (p = 0.0001) compared with later-born siblings with no brothers. Part of this
      association was due to a shorter gestation among later-born siblings with
      brothers. An explanation for these results could be maternal immune reactions
      directed against the H-Y antigens initiated during pregnancies with boys. The
      findings might add to the understanding of both normal and pathologic
      pregnancies.

PMID- 18048379
TI  - Dissecting the heterogeneity of schizophrenia outcomes.

PMID- 18048380
TI  - Editorial: research progress in early-onset schizophrenia.
AB  - A substantial proportion of patients with schizophrenia experience the onset of
      their illness by age 18. Data from phenomenological, cognitive, neuroimaging, and
      genetic studies suggest a similar profile of clinical and neurobiological
      abnormalities between early- and adult-onset patients. However, children and
      adolescents with schizophrenia have been found to have more severe premorbid
      neurodevelopmental abnormalities, worse long-term outcome, more cytogenetic
      anomalies, and potentially greater loading of family histories for schizophrenia
      and associated spectrum disorders than their adult counterparts. Together, these
      data support a hypothesis that early-onset schizophrenia may reflect a more
      severe form of the disorder associated with a greater genetic predisposition. It
      is anticipated that future imaging and genetic studies of this cohort will
      provide further insight into the neurodevelopmental origins of schizophrenia and
      the complexity by which genetic and environmental factors interact to modulate
      susceptibility and/or disease phenotype. The articles on this theme provide
      updated findings from brain magnetic resonance imaging, neurocognition, and
      clinical trials in this unique cohort.

PMID- 18048381
TI  - Metastases to the breast: role of fine needle cytology samples. Our experience
      with nine cases in 2 years.
AB  - BACKGROUND: The increased survival due to the introduction of effective
      antineoplastic regimens has caused a modification of the natural history of
      numerous malignancies. Follow-up of neoplastic patients often includes the
      evaluation of masses in various body sites by fine needle cytology (FNC) in order
      to rule out cancer recurrence. Besides primary neoplasms, the breast can host a
      number of metastases: these rarely do have a typical presentation, so FNC is
      requested for their cytomorphological assessment. PATIENTS AND METHODS: This
      report describes nine consecutive cases in which a cytopathological diagnosis of
      metastasis to the breast was carried out on FNC samples. RESULTS: Primary sites
      were identified on cytomorphological and immunocytochemical bases and were
      represented by the ovary (three cases), melanoma (two cases), endocervix (one
      case), endometrium (one case), lung (one case) and prostate (one case).
      CONCLUSION: The cytopathological diagnosis of metastatic neoplasms to the breast
      is not always straightforward, especially in the absence of a clinical history of
      cancer. The usage of improved cytopathological criteria combined with
      immunocytochemistry may be of great diagnostic help in the identification of
      breast metastases.

PMID- 18048382
TI  - Prognostic factors for hematotoxicity of chemotherapy in aggressive non-Hodgkin's
      lymphoma.
AB  - BACKGROUND: Little is known on the heterogeneity of hematotoxicity in patients
      receiving multicycle chemotherapy. PATIENTS AND METHODS: We analyzed data of 1399
      patients with aggressive lymphoma from trials using CHOP (combination
      chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone)-like
      therapies. Multivariate modeling was carried out for leukocytopenia,
      thrombocytopenia and anemia and the models were validated by two large
      independent datasets from trials with/without usage of the CD20-antibody
      rituximab. RESULTS: On the basis of these models, we are able to predict the
      remarkable heterogeneity of hematotoxicity and propose to use risk groups.
      Regarding leukocytopenia, the low toxicity risk group experienced World Health
      Organization grade 4 in <10% of the cycles while the high toxicity risk group in
      almost all cycles. For thrombocytopenia, groups were detectable with almost no
      grade 3 or 4 toxicity and others where two out of three cycles were affected. In
      a separate set of models, the first cycle toxicity was the strongest predictor
      for later hematotoxicity. The risk for leukocytopenia was associated with
      infections, antibiotic use, hospitalization and treatment-related mortality,
      indicating the clinical usefulness of the models. For the first time, a Web-based
      tool is made available to easily predict the hematotoxicity in clinical practice
      (www.toxcalculator.com). CONCLUSION: This analysis has implications for patient
      management and prophylaxis.

PMID- 18048383
TI  - The long-term risks of adjuvant carboplatin treatment for stage I seminoma of the
      testis.
AB  - BACKGROUND: The use of adjuvant carboplatin in the management of stage I seminoma
      of the testis has been limited by the lack of long-term data. In this study, we
      address this issue for the first time. PATIENTS AND METHODS: Data on 199 patients
      treated with single-agent carboplatin for stage I seminoma of the testis were
      prospectively collected. Overall mortality, deaths from circulatory disease and
      the incidence of second cancers were compared with expected values derived from
      the UK general population. RESULTS: The median follow-up for the cohort was 9.0
      years (range 0.1-20.1). There has been no excess in overall mortality
      [standardised mortality ratio (SMR) 0.89; 95% CI 0.36-1.83], death from
      circulatory diseases (SMR 1.44; 95% CI 0.39-3.69) or the incidence of second
      nontestis cancers (standardised incidence ratio 0.96; 95% CI 0.26-2.45) in this
      group of patients. These findings also applied to specific follow-up periods of
      >5 or 10 years. Specifically, neither haematological nor solid nontestis tumours
      occurred in excess. There was an increase in the long-term development of
      contralateral testis cancers. CONCLUSIONS: This study addresses some of the
      concerns surrounding the long-term safety of single-agent carboplatin. It also
      helps in planning long-term follow-up for patients receiving this form of
      treatment.

PMID- 18048384
TI  - Resveratrol-induced apoptosis depends on the lipid kinase activity of Vps34 and
      on the formation of autophagolysosomes.
AB  - In human colorectal DLD1 cancer cells, the dietary bioflavonoid resveratrol (RV)
      rapidly induced autophagy. This effect was reversible (on removal of the drug)
      and was associated with increased expression and cytosolic redistribution of the
      proteins Beclin1 and LC3 II. Supplementing the cells with asparagine (Asn)
      abrogated the Beclin-dependent autophagy. When applied acutely (2 h), RV was not
      toxic; however, reiterate chronic (48 h) exposure to RV eventually led to annexin
      V- and terminal deoxinucleotidyl transferase-mediated dUTP-biotin nick end
      labeling-positive cell death. This toxic effect was autophagy dependent, as it
      was prevented either by Asn, by expressing a dominant-negative lipid kinase
      deficient class III phosphoinositide 3-phosphate kinase, or by RNA interference
      knockdown of Beclin1. Lamp2b silencing abolished the fusion of autophagosomes
      with lysosomes and preserved cell viability despite the ongoing formation of
      autophagosomes in cells chronically exposed to RV. The pan-caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone inhibited RV-induced cell death,
      but not autophagy. These results uncover a novel pathway of RV cytotoxicity in
      which autophagy plays a dual role: (i) at first, it acts as a prosurvival stress
      response and (ii) at a later time, it switches to a caspase-dependent apoptosis
      pathway. The present data also indicate that genetic or epigenetic inactivation
      of autophagy proteins in cancer cells may confer resistance to RV-mediated
      killing.

PMID- 18048385
TI  - Integrated analysis of chromosomal, microsatellite and epigenetic instability in
      colorectal cancer identifies specific associations between promoter methylation
      of pivotal tumour suppressor and DNA repair genes and specific chromosomal
      alterations.
AB  - Colorectal cancer (CRC) is a complex and heterogeneous disease in which genomic
      instability and DNA promoter methylation play important roles. The aim of this
      study was to investigate the relationship between chromosomal instability (CIN),
      microsatellite instability (MSI) and promoter methylation of CRC-associated
      genes. Therefore, 71 CRCs were analysed for CIN and MSI by comparative genomic
      hybridization and the mononucleotide marker BAT-26, respectively. Promoter
      methylation of the tumour suppressor and DNA repair genes hMLH1, O(6)-MGMT, APC,
      p14(ARF), p16(INK4A), RASSF1A, GATA-4, GATA-5 and CHFR was analysed using
      methylation-specific polymerase chain reaction. These integrative analyses showed
      that in CIN+ CRCs, promoter methylation of GATA-4 and p16(INK4A) was inversely
      related to chromosomal loss at 15q11-q21 and gain at 20q13, respectively (P
      values: 3.8 x 10(-2) and 4.5 x 10(-2), respectively). Interestingly, promoter
      methylation of RASSF1A, GATA-4, GATA-5 and CHFR, as well as a high methylation
      index (MI), was positively related to chromosomal gain at 8q23-qter (P values:
      1.5 x 10(-2), 3.8 x 10(-2), 3.9 x 10(-2), 4.9 x 10(-2) and 8.2 x 10(-3),
      respectively). MSI was associated with BRAF mutation, promoter methylation of
      hMLH1, APC and p16(INK4A) and a high MI (total number of methylated genes) (P
      values: 2.4 x 10(-2), 2.5 x 10(-3), 1.8 x 10(-2), 4.6 x 10(-2) and 1.0 x 10(-2),
      respectively). Therefore, we conclude that promoter methylation of pivotal tumour
      suppressor and DNA repair genes is associated with specific patterns of
      chromosomal changes in CRC, which are different from methylation patterns in MSI
      tumours.

PMID- 18048386
TI  - Overexpression of cyclin B1 in human esophageal squamous cell carcinoma cells
      induces tumor cell invasive growth and metastasis.
AB  - Cyclin B1, a key component in the control of cell cycle progression from G(2) to
      M phase, has been implicated in tumorigenesis and the development of malignancy.
      However, the underlying mechanism by which cyclin B1 acts as an important
      oncogenic molecule remains largely unknown. Here we show that ectopic expression
      of cyclin B1 promotes cell proliferation, enhances cell motility and migration
      and results in increased ability of cells extravasating through the capillary
      endothelium. Interestingly, isogenic esophageal squamous cell carcinoma (ESCC)
      cells overexpressing cyclin B1 reveal strong invasive growth and high potential
      of metastasis to lung in xenograft mice. Suppression of cyclin B1 expression via
      small interfering RNA approach in high-metastatic esophagus carcinoma cells
      specifically inhibits their ability to metastasize from the primary ESCC to lung.
      Notably, altered expression of epithelial markers and mesenchymal markers were
      observed in the cells overexpressing cyclin B1, suggesting that cyclin B1
      contributes to metastasis probably by promoting an epithelial-mesenchymal
      transition. These results establish a mechanistic link between cyclin B1 and ESCC
      metastasis and provide novel insight into understanding of cyclin B1 in the
      development of ESCC malignancy.

PMID- 18048387
TI  - CDC6: from DNA replication to cell cycle checkpoints and oncogenesis.
AB  - Cell division cycle 6 (CDC6) is an essential regulator of DNA replication in
      eukaryotic cells. Its best-characterized function is the assembly of
      prereplicative complexes at origins of replication during the G(1) phase of the
      cell division cycle. However, CDC6 also plays important roles in the activation
      and maintenance of the checkpoint mechanisms that coordinate S phase and mitosis,
      and recent studies have unveiled its proto-oncogenic activity. CDC6
      overexpression interferes with the expression of INK4/ARF tumor suppressor genes
      through a mechanism involving the epigenetic modification of chromatin at the
      INK4/ARF locus. In addition, CDC6 overexpression in primary cells may promote DNA
      hyperreplication and induce a senescence response similar to that caused by
      oncogene activation. These findings indicate that deregulation of CDC6 expression
      in human cells poses a serious risk of carcinogenesis.

PMID- 18048388
TI  - Downregulation of Dkk3 activates beta-catenin/TCF-4 signaling in lung cancer.
AB  - Although the oncogenic role of the Wnt/beta-catenin pathway is well defined, it
      remains unclear how this pathway is aberrantly activated in lung cancer. We found
      that Dickkopf (Dkk)-3, a member of Dkk family of Wnt antagonists, is frequently
      inactivated in lung cancer and plays a role in suppressing lung cancer cell
      growth through inhibition of beta-catenin/T-cell factor (TCF)-4 signaling. Dkk3
      is the only Dkk family member abundantly expressed in normal lung, but silenced
      by promoter hypermethylation in a large fraction of lung cancer cell lines and
      lung tumors. Downregulation of Dkk3 was correlated with tumor progression and
      expression of nuclear beta-catenin in lung tumors. Ectopic expression of Dkk3 in
      lung cancer cells with Dkk3 hypermethylation induced apoptosis and inhibited TCF
      4 activity as well as nuclear accumulation of beta-catenin and expression of TCF
      4 targets c-Myc and cyclin D1. Furthermore, small interference RNA knock down of
      Dkk3 in cells lacking Dkk3 hypermethylation was sufficient to promote cell
      proliferation, beta-catenin nuclear translocation and expression of c-Myc. These
      observations suggested that epigenetic inactivation of Dkk3 activates the
      Wnt/beta-catenin pathway, thereby promoting the growth of lung cancer cells.

PMID- 18048389
TI  - In vitro and in vivo cytotoxic effects of PRIMA-1 on hepatocellular carcinoma
      cells expressing mutant p53ser249.
AB  - Hepatocellular carcinoma (HCC) is highly lethal due to limited curative options.
      In high-incidence regions, such as parts of Africa and Southeastern Asia, >50% of
      cases carry an AGG to AGT mutation at codon 249 of the TP53 gene, considered as a
      'signature' of mutagenesis by aflatoxins. The protein product, p53ser249, may
      represent a therapeutic target for HCC. The small molecule p53 reactivation and
      induction of massive apoptosis (PRIMA)-1 has been shown to induce apoptosis in
      tumour cells by reactivating the transactivation capacity of some p53 mutants. In
      this study, we have investigated the cytotoxic effects of PRIMA-1 on HCC cells
      expressing p53ser249. In p53-null Hep3B cells, over-expression of p53ser249 or
      p53gln248 by stable transfection increased the cytotoxicity of PRIMA-1 at 50 muM.
      Furthermore, PRIMA-1 treatment delayed the growth of p53ser249-expressing Hep3B
      cells xenografted in severe combined immunodeficiency mice. However, PRIMA-1 did
      not restore wild-type DNA binding and transactivation activities to p53ser249 or
      to p53gln248 in Hep3B cells. Moreover, in PLC/PRF/5, a HCC cell line
      constitutively expressing p53ser249, small interfering RNA (siRNA) silencing of
      the mutant increased the cytotoxic effect of PRIMA-1. These apparently
      contradictory effects can be reconciled by proposing that p53ser249 exerts a gain
      of-function effect, which favours the survival of HCC cells. Thus, both
      inhibition of this effect by PRIMA-1 and removal of the mutant by siRNA can lead
      to the decrease of survival capacity of HCC cells.

PMID- 18048390
TI  - Properties of the six isoforms of p63: p53-like regulation in response to
      genotoxic stress and cross talk with DeltaNp73.
AB  - TP63, a member of the TP53 gene family, encodes two groups of three isoforms
      (alpha, beta and gamma). The TAp63 isoforms act as transcription factors. The
      DeltaNp63 isoforms lack the main transcription activation domain and act as
      dominant-negative inhibitors of transactivation (TA) isoforms. To clarify the
      role of these isoforms and to better understand their functional overlap with
      p53, we ectopically expressed each p63 isoform in the p53-null hepatocellular
      carcinoma cell line Hep3B. All TA isoforms, as well as DeltaNp63alpha, had a half
      life of <1 h when transiently expressed and were degraded by the proteasome
      pathway. The most stable form was DeltaNp63gamma, with a half-life of >8 h. As
      expected, TA isoforms differed in their transcriptional activities toward genes
      regulated by p53, TAp63gamma being the most active form. In contrast, DeltaNp63
      isoforms were transcriptionally inactive on genes studied and inhibited TA
      isoforms in a dose-dependent manner. When stably expressed in polyclonal cell
      populations, TAp63beta and gamma isoforms were undetectable. However, when
      treated with doxorubicin (DOX), p63 proteins rapidly accumulated in the cells.
      This stabilization was associated with an increase in phosphorylation.
      Strikingly, in DOX-treated polyclonal populations, increase in TAp63 levels was
      accompanied by overexpression of DeltaNp73. This observation suggests complex
      regulatory cross talks between the different isoforms of the p53 family. In
      conclusion, p63 exhibits several transcriptional and stress-response properties
      similar to those of p53, suggesting that p63 activities should be taken into
      consideration in approaches to improve cancer therapies based on genotoxic
      agents.

PMID- 18048391
TI  - SAGE library screening reveals ILT7 as a specific plasmacytoid dendritic cell
      marker that regulates type I IFN production.
AB  - Plasmacytoid dendritic cells (pDCs) link innate to acquired immune responses by
      producing high levels of type I IFN upon infection. In order to identify the
      specific genes that control pDC, we compared serial analysis of gene expression
      libraries from human pDCs, herpes simplex virus-stimulated pDCs and monocytes. We
      found that Ig-like transcript ILT7 is specifically expressed on pDC cell surfaces
      and is down-regulated when pDC mature in response to viral or bacterial
      stimulation. ILT7 expression on the cell surface required association with the Fc
      epsilon RI gamma adaptor molecule. Although treatment with one anti-ILT7-specific
      mAb suppressed type I IFN production in response to cytosine-phosphate-guanosice
      (CpG) stimulation, another anti-ILT7 mAb up-regulated type I IFN production. We
      conclude that ILT7 is a key regulator of human pDC function.

PMID- 18048392
TI  - Is moderate drinking as effective as cholesterol lowering in reducing mortality
      in high-risk coronary patients?

PMID- 18048393
TI  - Prediction of both conserved and nonconserved microRNA targets in animals.
AB  - MOTIVATION: MicroRNAs (miRNAs) are involved in many diverse biological processes
      and they may potentially regulate the functions of thousands of genes. However,
      one major issue in miRNA studies is the lack of bioinformatics programs to
      accurately predict miRNA targets. Animal miRNAs have limited sequence
      complementarity to their gene targets, which makes it challenging to build target
      prediction models with high specificity. RESULTS: Here we present a new miRNA
      target prediction program based on support vector machines (SVMs) and a large
      microarray training dataset. By systematically analyzing public microarray data,
      we have identified statistically significant features that are important to
      target downregulation. Heterogeneous prediction features have been non-linearly
      integrated in an SVM machine learning framework for the training of our target
      prediction model, MirTarget2. About half of the predicted miRNA target sites in
      human are not conserved in other organisms. Our prediction algorithm has been
      validated with independent experimental data for its improved performance on
      predicting a large number of miRNA down-regulated gene targets. AVAILABILITY: All
      the predicted targets were imported into an online database miRDB, which is
      freely accessible at http://mirdb.org.

PMID- 18048394
TI  - TOM: enhancement and extension of a tool suite for in silico approaches to
      multigenic hereditary disorders.
AB  - The study of complex hereditary diseases is a very challenging area of research.
      The expanding set of in silico approaches offers a flourishing ground for the
      acceleration of meaningful findings in this area by exploitation of rich and
      diverse sources of omic data. These approaches are cheap, flexible, extensible,
      often complementary and can continuously integrate new information and tests to
      improve the selection of genes responsible for hereditary diseases. Following
      this principle, we improved and extended our web-service TOM for the
      identification of candidate genes in the study of complex hereditary diseases.
      AVAILABILITY: Our tool is freely available online at
      http://www.micrel.deis.unibo.it/~tom/.

PMID- 18048395
TI  - MutaGeneSys: estimating individual disease susceptibility based on genome-wide
      SNP array data.
AB  - We present MutaGeneSys: a system that uses genome-wide genotype data to estimate
      disease susceptibility. Our system integrates three data sources: the
      International HapMap project, whole-genome marker correlation data and the Online
      Mendelian Inheritance in Man (OMIM) database. It accepts SNP data of individuals
      as query input and delivers disease susceptibility hypotheses even if the
      original set of typed SNPs is incomplete. Our system is scalable and flexible: it
      produces population, technology and confidence-specific predictions in
      interactive time. AVAILABILITY: Our system is available as an online resource at
      http://magnet.c2b2.columbia.edu/mutagenesys/. Our findings have also been
      incorporated into the HapMap Genome Browser as the OMIM_Disease_Associations
      track.

PMID- 18048396
TI  - An efficient strategy for extensive integration of diverse biological data for
      protein function prediction.
AB  - MOTIVATION: With the increasing availability of diverse biological information,
      protein function prediction approaches have converged towards integration of
      heterogeneous data. Many adapted existing techniques, such as machine-learning
      and probabilistic methods, which have proven successful on specific data types.
      However, the impact of these approaches is hindered by a couple of factors.
      First, there is little comparison between existing approaches. This is in part
      due to a divergence in the focus adopted by different works, which makes
      comparison difficult or even fuzzy. Second, there seems to be over-emphasis on
      the use of computationally demanding machine-learning methods, which runs counter
      to the surge in biological data. Analogous to the success of BLAST for sequence
      homology search, we believe that the ability to tap escalating quantity, quality
      and diversity of biological data is crucial to the success of automated function
      prediction as a useful instrument for the advancement of proteomic research. We
      address these problems by: (1) providing useful comparison between some prominent
      methods; (2) proposing Integrated Weighted Averaging (IWA)--a scalable, efficient
      and flexible function prediction framework that integrates diverse information
      using simple weighting strategies and a local prediction method. The simplicity
      of the approach makes it possible to make predictions based on on-the-fly
      information fusion. RESULTS: In addition to its greater efficiency, IWA performs
      exceptionally well against existing approaches. In the presence of cross-genome
      information, which is overwhelming for existing approaches, IWA makes even better
      predictions. We also demonstrate the significance of appropriate weighting
      strategies in data integration.

PMID- 18048397
TI  - Mobius: an integrated discrete-event modeling environment.
AB  - Mobius has found numerous applications in computational biology to build and
      solve stochastic models of biological processes. It provides the user with a
      modeling workflow and several sophisticated features that are not available in
      the simulation tools commonly used by computational biologists. AVAILABILITY:
      Mobius is free for academic users. It can be downloaded from www.mobius.uiuc.edu

PMID- 18048398
TI  - Monte Carlo feature selection for supervised classification.
AB  - MOTIVATION: Pre-selection of informative features for supervised classification
      is a crucial, albeit delicate, task. It is desirable that feature selection
      provides the features that contribute most to the classification task per se and
      which should therefore be used by any classifier later used to produce
      classification rules. In this article, a conceptually simple but computer
      intensive approach to this task is proposed. The reliability of the approach
      rests on multiple construction of a tree classifier for many training sets
      randomly chosen from the original sample set, where samples in each training set
      consist of only a fraction of all of the observed features. RESULTS: The
      resulting ranking of features may then be used to advantage for classification
      via a classifier of any type. The approach was validated using Golub et al.
      leukemia data and the Alizadeh et al. lymphoma data. Not surprisingly, we
      obtained a significantly different list of genes. Biological interpretation of
      the genes selected by our method showed that several of them are involved in
      precursors to different types of leukemia and lymphoma rather than being genes
      that are common to several forms of cancers, which is the case for the other
      methods. AVAILABILITY: Prototype available upon request.

PMID- 18048399
TI  - A bias in ML estimates of branch lengths in the presence of multiple signals.
AB  - Sequence data often have competing signals that are detected by network programs
      or Lento plots. Such data can be formed by generating sequences on more than one
      tree, and combining the results, a mixture model. We report that with such
      mixture models, the estimates of edge (branch) lengths from maximum likelihood
      (ML) methods that assume a single tree are biased. Based on the observed number
      of competing signals in real data, such a bias of ML is expected to occur
      frequently. Because network methods can recover competing signals more
      accurately, there is a need for ML methods allowing a network. A fundamental
      problem is that mixture models can have more parameters than can be recovered
      from the data, so that some mixtures are not, in principle, identifiable. We
      recommend that network programs be incorporated into best practice analysis,
      along with ML and Bayesian trees.

PMID- 18048400
TI  - Widespread evolutionary conservation of alternatively spliced exons in
      Caenorhabditis.
AB  - Alternative splicing (AS) contributes to increased transcriptome and proteome
      diversity in various eukaryotic lineages. Previous studies showed low levels of
      conservation of alternatively spliced (cassette) exons within mammals and within
      dipterans. We report a strikingly different pattern in Caenorhabditis nematodes
      more than 92% of cassette exons from Caenorhabditis elegans are conserved in
      Caenorhabditis briggsae and/or Caenorhabditis remanei. High levels of
      conservation extend to minor-form exons (present in a minority of transcripts)
      and are particularly pronounced for exons showing complex patterns of splicing.
      The functionality of the vast majority of cassette exons is underscored by
      various other features. We suggest that differences in conservation between
      lineages reflect differences in levels of functionality and further suggest that
      these differences are due to differences in intron length and the strength of
      consensus boundaries across lineages. Finally, we demonstrate an inverse
      relationship between AS and gene duplication, suggesting that the latter may be
      primarily responsible for the emergence of new functional transcripts in
      nematodes.

PMID- 18048401
TI  - Duplication of accelerated evolution and growth hormone gene in passerine birds.
AB  - We report the discovery of a duplication of the growth hormone (GH) gene in a
      major group of birds, the passerines (Aves: Passeriformes). Phylogenetic analysis
      of 1.3-kb partial DNA sequences of GH genes for 24 species of passerines and
      numerous outgroups indicates that the duplication occurred in the ancestral
      lineage of extant passerines. Both duplicates and their open-reading frames are
      preserved throughout the passerine clade, and both duplicates are expressed in
      the zebra finch brain, suggesting that both are likely to be functional. The
      estimated rates of amino acid evolution are more than 10-fold higher in passerine
      GH genes than in those of their closest nonpasserine relatives. In addition,
      although the 84 codons sequenced are generally highly conserved for both
      passerines and nonpasserines, comparisons of the nonsynonymous/synonymous
      substitution ratios and the rate of predicted amino acid changes indicate that
      the 2 gene duplicates are evolving under different selective pressures and may be
      functionally divergent. The evidence of differential selection, coupled with the
      preservation of both gene copies in all major lineages since the origin of
      passerines, suggests that the duplication may be of adaptive significance, with
      possible implications for the explosive diversification of the passerine clade.

PMID- 18048402
TI  - Codon usage in mitochondrial genomes: distinguishing context-dependent mutation
      from translational selection.
AB  - We analyze the frequencies of synonymous codons in animal mitochondrial genomes,
      focusing particularly on mammals and fish. The frequencies of bases at 4-fold
      degenerate sites are found to be strongly influenced by context-dependent
      mutation, which causes correlations between pairs of neighboring bases. There is
      a pattern of excess of certain dinucleotides and deficit of others that is
      consistent across large numbers of species, despite the wide variation of single
      nucleotide frequencies among species. In many bacteria, translational selection
      is an important influence on codon usage. In order to test whether translational
      selection also plays a role in mitochondria, we need to control for context
      dependent mutation. Selection for translational accuracy can be detected by
      comparison of codon usage in conserved and variable sites in the same genes. We
      give a test of this type that works in the presence of context-dependent
      mutation. There is very little evidence for translational accuracy selection in
      the mitochondrial genes considered here. Selection for translational efficiency
      might lead to preference for codons that match the limited repertoire of
      anticodons on the mitochondrial tRNAs. This is difficult to detect because the
      effect would usually be in the same direction in comparable to codon families and
      so would not cause an observable difference in codon usage between families.
      Several lines of evidence suggest that this type of selection is weak in most
      cases. However, we found several cases where unusual bases occur at the wobble
      position of the tRNA, and in these cases, some evidence for selection on codon
      usage was found. We discuss the way that these unusual cases are associated with
      codon reassignments in the mitochondrial genetic code.

PMID- 18048403
TI  - Phylogenetic comparison of huntingtin homologues reveals the appearance of a
      primitive polyQ in sea urchin.
AB  - Huntingtin is a completely soluble 3,144 amino acid (aa) protein characterized by
      the presence of an amino-terminal polymorphic polyglutamine (polyQ) tract, whose
      aberrant expansion causes the progressively neurodegenerative Huntington's
      disease (HD). Biological evidence indicates that huntingtin (htt) is beneficial
      to cells (particularly to brain neurons) and that loss of its neuronal function
      may contribute to HD. The exact protein domains involved in its neuroprotective
      function are unknown. Evolutionary analyses of htt primary aa have so far been
      limited to a few species, but its thorough assessment may help to clarify the
      functions emerging during evolution. We made an extensive comparative analysis of
      the available htt protein homologues from different organisms along the metazoan
      phylogenetic tree and defined the presence of 3 different conservative blocks
      corresponding to human htt aa 1-386 (htt1), 683-1,586 (htt2), and 2,437-3,078
      (htt3), in which HEAT (Huntingtin, Elongator factor3, the regulatory A subunit of
      protein phosphatase 2A, and TOR1) repeats are well conserved. We also describe
      the cloning and sequencing of sea urchin htt mRNA, the oldest deuterostome
      homologue so far available. Multiple alignment shows the first appearance of a
      primitive polyQ in sea urchin, which predates an ancestral polyQ sequence in a
      nonchordate environment and defines the polyQ characteristic as being typical of
      the deuterostome branch. The fact that glutamines have conserved positions in
      deuterostomes and the polyQ size increases during evolution suggests that the
      protein has a possibly Q-dependent role. Finally, we report an evident relaxing
      constraint of the N-terminal block in Ciona and drosophilids that correlates with
      the absence of polyQ and which may indicate that the N-terminal portion of htt
      has evolved different functions in Ciona and protostomes.

PMID- 18048404
TI  - Multiple recombining loci encode MaSp1, the primary constituent of dragline silk,
      in widow spiders (Latrodectus: Theridiidae).
AB  - Spiders spin a functionally diverse array of silk fibers, each composed of one or
      more unique proteins. Most of these proteins, in turn, are encoded by members of
      a single gene family thought to have arisen through duplication and divergence of
      an ancestral silk gene. Because of its remarkable mechanical properties, orb
      weaver dragline silk, a composite of 2 proteins (MaSp1 and MaSp2), is the best
      studied. Here, we demonstrate that multiple loci encode MaSp1 in widow spiders
      (Latrodectus). Because these copies may be the result of more recent duplication
      events than those leading to the currently recognized silk gene paralogs, they
      offer insight into the early evolutionary fate of silk gene duplicates. In
      addition to 3 presumed functional MaSp1 loci in Latrodectus hesperus (Western
      black widow) and Latrodectus geometricus (brown widow) genomes, we find a MaSp1
      pseudogene in L. hesperus, demonstrating the potential for unrecognized
      extinction of silk gene paralogs. We also document recombination events among L.
      hesperus MaSp1 loci and between Latrodectus MaSp1 loci and MaSp2. This result
      supports the hypothesis that concerted evolution occurs not only within an
      individual silk gene but also among silk gene paralogs. One of the L. geometricus
      MaSp1 copies encodes a protein that has diverged in amino acid composition and
      potentially converged on the secondary structure of MaSp2. Based on the presence
      of multiple MaSp1 loci and the phylogenetic distribution of MaSp1 versus MaSp2,
      we propose that MaSp2 is derived from an ancestral MaSp1 duplicate. Finally,
      divergence has occurred in the upstream flanking sequences of the L. hesperus
      MaSp1 loci, the region most likely to contain regulatory motifs, providing ample
      opportunity for differential expression. However, the benefits associated with
      increased protein production may be the primary mechanism maintaining multiple
      functional MaSp1 copies in widow genomes.

PMID- 18048405
TI  - Sensitive quantitation of isoglobotriaosylceramide in the presence of isobaric
      components using electrospray ionization-ion trap mass spectrometry.
AB  - Isoglobotriaosylceramide (iGb3) is a stimulatory antigen for a unique type of T
      cell, Natural Killer T cells. Produced in the lysosomal compartment by mammalian
      antigen-presenting cells, iGb3 is one of the few clearly identified carbohydrate
      ligands for biological receptors. A major source of glycoconjugate structural
      diversity arises from the possibility of forming different linkages between the
      same monosaccharide units. Globotriaosylceramide (Gb3) exists as a natural isomer
      for iGb3, and both isomers are frequently found together in mixtures of
      glycosphingolipids extracted from mammalian cell membranes. Discriminating these
      isomers has been feasible using monoclonal antibodies raised against specific
      carbohydrate epitopes, or by unambiguous structural characterization, which
      requires relatively large amounts of pure compounds isolated from grams, or tens
      of grams, of biological samples. However, the precise detection of iGb3 from
      small amounts of biological samples, where it may be mixed with Gb3 present in
      much higher abundance, is a prerequisite for answering further important
      biological questions such as stimulation of NKT cells. Here we describe a
      specific and sensitive method based on ion trap mass spectrometry to discriminate
      iGb3 from Gb3. We also demonstrate its application to quantifying the amount of
      iGb3 in a prototype antigen-presenting cell, rat RBL-CD1d cells, using a
      chemically synthesized short N-acyl chain iGb3 as internal standard. This
      methodology may have wide implications for functional glycosphingolipidomics of
      immune cells and glycosphingolipid biomarker analysis.

PMID- 18048406
TI  - Susceptibility to coronary artery disease and diabetes is encoded by distinct,
      tightly linked SNPs in the ANRIL locus on chromosome 9p.
AB  - Genome-wide association studies have identified a region on chromosome 9p that is
      associated with coronary artery disease (CAD). The region is also associated with
      type 2 diabetes (T2D), a risk factor for CAD, although different SNPs were
      reported to be associated to each disease in separate studies. We have undertaken
      a case-control study in 4251 CAD cases and 4443 controls in four European
      populations using previously reported ('literature') and tagging SNPs. We
      replicated the literature SNPs (P = 8x10(-13); OR = 1.29; 95% CI: 1.20-1.38) and
      showed that the strong consistent association detected by these SNPs is a
      consequence of a 'yin-yang' haplotype pattern spanning 53 kb. There was no
      evidence of additional CAD susceptibility alleles over the major risk haplotype.
      CAD patients without myocardial infarction (MI) showed a trend towards stronger
      association than MI patients. The CAD susceptibility conferred by this locus did
      not differ by sex, age, smoking, obesity, hypertension or diabetes. A
      simultaneous test of CAD and diabetes susceptibility with CAD and T2D-associated
      SNPs indicated that these associations were independent of each other. Moreover,
      this region was not associated with differences in plasma levels of low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, fibrinogen,
      albumin, uric acid, bilirubin or homocysteine, although the CAD-high-risk allele
      was paradoxically associated with lower triglyceride levels. A large antisense
      non-coding RNA gene (ANRIL) collocates with the high-risk haplotype, is expressed
      in tissues and cell types that are affected by atherosclerosis and is a prime
      candidate gene for the chromosome 9p CAD locus.

PMID- 18048407
TI  - Comprehensive analysis of the role of DNA repair gene polymorphisms on risk of
      glioma.
AB  - Much of the variation in inherited risk of glioma is likely to be explained by
      combinations of common low risk variants. The established relationship between
      glioma risk and exposure to ionizing radiation led us to examine whether variants
      in the DNA repair genes contribute to disease susceptibility. We evaluated 1127
      haplotype-tagging single-nucleotide polymorphisms (SNPs) supplemented with 388
      putative functional SNPs to capture most of the common variation in 136 DNA
      repair genes, in five unique case-control series from four different countries
      (1013 cases, 1016 controls). We identified 16 SNPs associated with glioma risk at
      the 1% significance level. The highest association observed across the five
      independent case-control datasets involved rs243356, which maps to intron 3 of
      CHAF1A (trend odds ratio, 1.32; 95% confidence interval 1.14-1.54; P = 0.0002;
      false-positive report probability = 0.055, based on a prior probability of 0.01).
      Our results provide additional support for the hypothesis that low penetrance
      variants contribute to the risk of developing glioma and suggest that a genetic
      variant located in or around the CHAF1A gene contributes to disease risk.

PMID- 18048408
TI  - Haemoglobin S and haemoglobin C: 'quick but costly' versus 'slow but gratis'
      genetic adaptations to Plasmodium falciparum malaria.
AB  - Haemoglobin S (HbS; beta6Glu-->Val) and HbC (beta6Glu-->Lys) strongly protect
      against clinical Plasmodium falciparum malaria. HbS, which is lethal in
      homozygosity, has a multi-foci origin and a widespread geographic distribution in
      sub-Saharan Africa and Asia whereas HbC, which has no obvious CC segregational
      load, occurs only in a small area of central West-Africa. To address this
      apparent paradox, we adopted two partially independent haplotypic approaches in
      the Mossi population of Burkina Faso where both the local S (S(Benin)) and the C
      alleles are common (0.05 and 0.13). Here we show that: both C and S(Benin) are
      monophyletic; C has accumulated a 4-fold higher recombinational and DNA slippage
      haplotypic variability than the S(Benin) allele (P = 0.003) implying higher
      antiquity; for a long initial lag period, the C alleles did apparently remain
      very few. These results, consistent with epidemiological evidences, imply that
      the C allele has been accumulated mainly through a recessive rather than a
      semidominant mechanism of selection. This evidence explains the apparent paradox
      of the uni-epicentric geographic distribution of HbC, representing a 'slow but
      gratis' genetic adaptation to malaria through a transient polymorphism, compared
      to the polycentric 'quick but costly' adaptation through balanced polymorphism of
      HbS.

PMID- 18048409
TI  - Reactivity of integrin-linked kinase in human mesothelial cell proliferation.
AB  - Integrin-linked kinase (ILK) is a protein kinase that links integrins and growth
      factors to a range of signalling pathways. ILK expression and activity are
      increased in a variety of human cancers. However, little is known regarding the
      role of ILK in malignant pleural mesothelioma (MPM). In this study, we assessed
      the expression of ILK in samples of human MPM, and compared it with the
      expression of epidermal growth factor receptor (EGFR). Thirty-four samples of
      human malignant mesothelioma were stained with a polyclonal antibody against ILK.
      Two independent observers evaluated the morphological pattern and intensity of
      staining. The findings have been compared with the patient's characteristics.
      Most MPM and mesothelial cell proliferation samples (87.9%) showed cytoplasmic
      ILK staining of varying intensity. Normal mesothelial cells and normal lung
      parenchyma did not stain for ILK at all. Conversely, the percentage of positive
      EGFR staining was somewhat lower (75.8%). The ILK-positive patients were
      significantly older than the ILK-negative patients. Here we report for the first
      time that ILK is indeed expressed in malignant mesothelioma. For further
      validation of a causal association between ILK and neoplastic mesothelial
      transformation, these immunohistochemical results should be supplemented with
      clinical and molecular biological data.

PMID- 18048410
TI  - Radical surgery for malignant pleural mesothelioma: results and prognosis.
AB  - The role of surgical treatment for malignant pleural mesothelioma (MPM) continues
      to be controversial. We carried out a retrospective review of the prognosis in
      patients who had radical surgery for MPM. Of 87 consecutive patients on whom
      surgical exploration for biopsy-proven MPM was performed, 31 patients underwent
      extrapleural pneumonectomy (EPP) and 34 patients underwent
      pleurectomy/decortication (P/D). Sixty-five patients having EPP or P/D included
      58 men (89%). The median age was 60 years (range 35-78) and the histologic type
      was epithelial in 48 patients (74%). IMIG staging classification was p-stage I
      disease in eight patients (12%), p-stage II in 13 (20%), p-stage III in 40 (62%)
      and p-stage IV in 4 (6%). Operative mortality was 3.2% for EPP and none for P/D.
      The median and 3-year survivals after EPP were 13 months and 33% whereas those
      after P/D were 17 months and 24%, respectively. A multivariate analysis
      demonstrated that older age (P=0.0467), non-epithelial histology (P=0.0057) and p
      stage III-IV disease (P=0.0019), but not gender, side, surgical procedure, were
      significant independent negative prognostic factors. Although P/D appears to be
      acceptable in early stages, we encourage EPP, en bloc resection without entering
      the pleural cavity with intent for curability, which provides oncologically
      complete resection of all disease.

PMID- 18048411
TI  - Calcium efflux as a component of the hypersensitive response of Nicotiana
      benthamiana to Pseudomonas syringae.
AB  - Using a model plant Nicotiana benthamiana, we have demonstrated that initial
      calcium uptake in response to the HR (hypersensitive response)-causing pathogen
      Pseudomonas syringae pv syringae 61 is followed by net calcium efflux initiated
      at about 12 h after the bacterial challenge and sustained for at least 48 h. Our
      data suggest that calcium not only acts as an important second messenger in the
      activation of resistance responses but may also be a downstream mediator of later
      cell death acceleration and completion of the defense reaction. Accordingly, we
      propose that the existing model of HR should be amended to include a PM Ca(2+)
      ATP pump as an important component of the HR to pathogens in plants.

PMID- 18048412
TI  - DrugBank: a knowledgebase for drugs, drug actions and drug targets.
AB  - DrugBank is a richly annotated resource that combines detailed drug data with
      comprehensive drug target and drug action information. Since its first release in
      2006, DrugBank has been widely used to facilitate in silico drug target
      discovery, drug design, drug docking or screening, drug metabolism prediction,
      drug interaction prediction and general pharmaceutical education. The latest
      version of DrugBank (release 2.0) has been expanded significantly over the
      previous release. With approximately 4900 drug entries, it now contains 60% more
      FDA-approved small molecule and biotech drugs including 10% more 'experimental'
      drugs. Significantly, more protein target data has also been added to the
      database, with the latest version of DrugBank containing three times as many non
      redundant protein or drug target sequences as before (1565 versus 524). Each
      DrugCard entry now contains more than 100 data fields with half of the
      information being devoted to drug/chemical data and the other half devoted to
      pharmacological, pharmacogenomic and molecular biological data. A number of new
      data fields, including food-drug interactions, drug-drug interactions and
      experimental ADME data have been added in response to numerous user requests.
      DrugBank has also significantly improved the power and simplicity of its
      structure query and text query searches. DrugBank is available at
      http://www.drugbank.ca.

PMID- 18048413
TI  - The dual control of TFIIB recruitment by NC2 is gene specific.
AB  - Negative co-factor 2 (NC2) is a conserved eukaryotic complex composed of two
      subunits, NC2alpha (Drap1) and NC2beta (Dr1) that associate through a histone
      fold motif. In this work, we generated mutants of NC2, characterized target genes
      for these mutants and studied the assembly of NC2 and general transcription
      factors on target promoters. We determined that the two NC2 subunits mostly
      function together to be recruited to DNA and regulate gene expression. We found
      that NC2 strongly controls promoter association of TFIIB, both negatively and
      positively. We could attribute the gene-specific repressor effect of NC2 on TFIIB
      to the C-terminal domain of NC2beta, and define that it requires ORF sequences of
      the target gene. In contrast, the positive function of NC2 on TFIIB targets is
      more general and requires adequate levels of the NC2 histone-fold heterodimer on
      promoters. Finally, we determined that NC2 becomes limiting for TATA-binding
      protein (TBP) association with a heat inducible promoter under heat stress. This
      study demonstrates an important positive role of NC2 for formation of the pre
      initiation complex on promoters, under normal conditions through control of
      TFIIB, or upon activation by stress via control of TBP.

PMID- 18048414
TI  - The RNA-dependent RNA polymerase essential for post-transcriptional gene
      silencing in Neurospora crassa interacts with replication protein A.
AB  - Post-transcriptional gene silencing (PTGS) pathways play a role in genome defence
      and have been extensively studied, yet how repetitive elements in the genome are
      identified is still unclear. It has been suggested that they may produce aberrant
      transcripts (aRNA) that are converted by an RNA-dependent RNA polymerase (RdRP)
      into double-stranded RNA (dsRNA), the essential intermediate of PTGS. However,
      how RdRP enzymes recognize aberrant transcripts remains a key question. Here we
      show that in Neurospora crassa the RdRP QDE-1 interacts with Replication Protein
      A (RPA), part of the DNA replication machinery. We show that both QDE-1 and RPA
      are nuclear proteins and that QDE-1 is specifically recruited onto the repetitive
      transgenic loci. We speculate that this localization of QDE-1 could allow the in
      situ production of dsRNA using transgenic nascent transcripts as templates, as in
      other systems. Supporting a link between the two proteins, we found that the
      accumulation of short interfering RNAs (siRNAs), the hallmark of silencing, is
      dependent on an ongoing DNA synthesis. The interaction between QDE-1 and RPA is
      important since it should guide further studies aimed at understanding the
      specificity of the RdRP and it provides for the first time a potential link
      between a PTGS component and the DNA replication machinery.

PMID- 18048415
TI  - Mechanisms of covalent self-assembly of the Azoarcus ribozyme from four fragment
      oligonucleotides.
AB  - RNA oligomers of length 40-60 nt can self-assemble into covalent versions of the
      Azoarcus group I intron ribozyme. This process requires a series of recombination
      reactions in which the internal guide sequence of a nascent catalytic complex
      makes specific interactions with a complement triplet, CAU, in the oligomers.
      However, if the CAU were mutated, promiscuous self-assembly may be possible,
      lessening the dependence on a particular set of oligomer sequences. Here, we
      assayed whether oligomers containing mutations in the CAU triplet could still
      self-construct Azoarcus ribozymes. The mutations CAC, CAG, CUU and GAU all
      inhibited self-assembly to some degree, but did not block it completely in 100 mM
      MgCl(2). Oligomers containing the CAC mutation retained the most self-assembly
      activity, while those containing GAU retained the least, indicating that
      mutations more 5' in this triplet are the most deleterious. Self-assembly systems
      containing additional mutant locations were progressively less functional.
      Analyses of properly self-assembled ribozymes revealed that, of two recombination
      mechanisms possible for self-assembly, termed 'tF2' and 'R2F2', the simpler one
      step 'tF2' mechanism is utilized when mutations exist. These data suggest that
      self-assembling systems are more facile than previously believed, and have
      relevance to the origin of complex ribozymes during the RNA World.

PMID- 18048416
TI  - ATR-dependent pathways control hEXO1 stability in response to stalled forks.
AB  - Nucleases play important roles in DNA synthesis, recombination and repair. We
      have previously shown that human exonuclease 1 (hEXO1) is phosphorylated in
      response to agents stalling DNA replication and that hEXO1 consequently undergoes
      ubiquitination and degradation in a proteasome-dependent manner. In the present
      study, we have addressed the identity of the pathway transducing stalled
      replication signals to hEXO1. Using chemical inhibitors, RNA interference, ATM-
      and ATR-deficient cell lines we have concluded that hEXO1 phosphorylation is ATR
      dependent. By means of mass spectrometry, we have identified the sites of
      phosphorylation in hEXO1 in undamaged cells and in cells treated with hydroxyurea
      (HU). hEXO1 is phosphorylated at nine basal sites and three additional sites are
      induced by HU treatment. Analysis of single- and multiple-point mutants revealed
      that mutation to Ala of the three HU-induced sites of phosphorylation partially
      rescued HU-dependent degradation of hEXO1 and additionally stabilized the protein
      in non-treated cells. We have raised an antibody to pS(714), an HU-induced site
      of the S/T-Q type, and we provide evidence that S(714) is phosphorylated upon HU
      but not IR treatment. The antibody may be a useful tool to monitor signal
      transduction events triggered by stalled DNA replication.

PMID- 18048417
TI  - Interplay of ion binding and attraction in DNA condensed by multivalent cations.
AB  - We have measured forces generated by multivalent cation-induced DNA condensation
      using single-molecule magnetic tweezers. In the presence of cobalt hexammine,
      spermidine, or spermine, stretched DNA exhibits an abrupt configurational change
      from extended to condensed. This occurs at a well-defined condensation force that
      is nearly equal to the condensation free energy per unit length. The multivalent
      cation concentration dependence for this condensation force gives the apparent
      number of multivalent cations that bind DNA upon condensation. The measurements
      show that the lower critical concentration for cobalt hexammine as compared to
      spermidine is due to a difference in ion binding, not a difference in the
      electrostatic energy of the condensed state as previously thought. We also show
      that the resolubilization of condensed DNA can be described using a traditional
      Manning-Oosawa cation adsorption model, provided that cation-anion pairing at
      high electrolyte concentrations is taken into account. Neither overcharging nor
      significant alterations in the condensed state are required to describe the
      resolubilization of condensed DNA. The same model also describes the
      spermidine3+/Na+ phase diagram measured previously.

PMID- 18048419
TI  - Evidence for sustained renal hypoxia and transient hypoxia adaptation in
      experimental rhabdomyolysis-induced acute kidney injury.
AB  - BACKGROUND: Indirect evidence suggests that hypoxia contributes to the
      pathophysiology of rhabdomyolysis-induced acute kidney injury (AKI). However, the
      cellular location and kinetics of hypoxia, as well as potential hypoxia
      adaptation are unclear. METHODS: Rhabdomyolysis was induced in rats by IM
      glycerol (GLY) injection, which largely recapitulates the full clinical syndrome.
      Additional rats received IV myoglobin (MYO), in order to assess the contribution
      of MYO per se. We performed immunohistochemistry for hypoxia markers
      [pimonidazole (PIM) adducts and hypoxia-inducible factors (HIFs)] and the cell
      protective HIF target gene heme oxygenase-1 (HO-1). Furthermore, we sought a
      potential negative feedback loop to terminate HIF activation, driven by HIF
      prolyl-hydroxylase-2 (PHD-2). RESULTS: In GLY, progressive tubular injury, mainly
      of proximal tubules (PT), developed over time, but its extent was heterogeneous.
      PIM, HIFalpha and HO-1 were all absent in controls, but strongly positive in GLY,
      with a specific spatio-temporal pattern. In PT, (a) PIM was detectable throughout
      the study with a maximum at 6 h, (b) HIF was activated only at 3 h and (c) HO-1
      and PHD-2 appeared at 6 h and persisted at a lower level at 24 h. Apart from
      tubular cast formation, MYO did not cause overt tissue damage, but led to strong
      activation of HIFs, in a pattern similar to 3 h of GLY. CONCLUSIONS: Our data
      suggest that renal hypoxia occurs in rhabdomyolysis, and that MYO, at least
      partly, contributes to hypoxia generation. Since in the most affected tubules
      transcriptional hypoxia adaptation is transient and inhomogeneous, pharmacologic
      HIF enhancement holds the potential to improve outcome in rhabdomyolysis-induced
      AKI.

PMID- 18048420
TI  - Dialysis-related systemic microinflammation is associated with specific genomic
      patterns.
AB  - BACKGROUND: Although several reports have focused on the clinical importance of
      the systemic microinflammatory state in the uraemic population, the relationship
      between the activation of a specific transcriptome and the development of this
      condition is still not completely defined. METHODS: Thirty haemodialysis (HD), 30
      peritoneal dialysis (PD) and 30 chronic kidney disease (CKD) patients were
      enrolled in our study. For all patients, serum C-reactive protein (CRP) and
      ferritin levels were determined. In addition, the expression level of 234
      inflammatory responses and oxidative stress pathway genes was measured, using
      oligonucleotide microarray chips (HG-U133A, Affymetrix), in peripheral blood
      mononuclear cells of 24 randomly selected patients (8 HD, 8 PD and 8 CKD).
      RESULTS: HD patients demonstrated higher CRP and ferritin levels compared to PD
      and CKD patients (P < 0.001). Statistical analysis identified 10 genes able to
      discriminate CKD from HD and PD patients (FDR = 5%, P < 0.001) and significantly
      correlated to CRP levels. All together, these genes were able to predict
      inflammation with an accuracy of 87% (P < 0.001). Among the selected genes there
      were those encoding for key regulators of inflammation and oxidative stress (e.g.
      RELA, GSS). Interestingly, only three inflammatory genes (MIF, IL8RB and CXCL12)
      were still significantly associated with inflammation when included in a
      multivariate analysis. RT-PCR for RELA, MIF, CXCL12 and western blots for IL8RB
      and GSS, using 66 patients, validated the microarray results. CONCLUSIONS: This
      study may help to better understand the physiopathology of the systemic
      inflammatory state in CKD and dialysis patients and to identify new target genes
      potentially useful for future bio-molecular studies and therapeutic approaches.

PMID- 18048421
TI  - Acute effects of low and high intravenous doses of furosemide on myocardial
      function in anuric haemodialysis patients: a tissue Doppler study.
AB  - BACKGROUND: In patients with pulmonary oedema and preserved renal function,
      furosemide has not only a renal, but also a vascular effect, causing a rapid fall
      in left ventricular filling pressure accompanied by an increase in venous
      compliance. Previous studies have shown conflicting findings regarding the
      vascular effects of furosemide in patients with end-stage renal disease (ESRD).
      The objective of our study was to investigate whether furosemide induces changes
      in central cardiac haemodynamics in anuric ESRD patients, using conventional
      echocardiography and colour tissue Doppler velocity imaging (TVI), a new
      quantitative and sensitive method. METHODS: Repeated low doses (40 mg followed by
      an additional dose of 40 mg after 30 min) of i.v. furosemide were administered to
      12 (61.6 +/- 16 years, 7 men) and a high dose (250 mg) of i.v. furosemide to 6
      (64.1 +/- 3.6 years, 5 men) clinically stable anuric haemodialysis (HD) patients.
      Conventional two-dimensional echocardiography and colour TVI images were recorded
      immediately before (0 min) the furosemide infusion in both groups, and in the
      group receiving the repeated low-dose infusion (at 0 and 30 min), 10, 20, 30, 40,
      50 and 70 min after the administration of the first infusion. In the group
      receiving the single high dose of furosemide the ultrasound investigation was
      repeated 10, 20, 30 and 40 min after the infusion. The myocardial tissue
      velocities (v; cm/s) for isovolumetric contraction (IVC), peak systole (PS),
      early (E') and late (A') myocardial diastolic filling velocities were measured in
      the left ventricle (LV) at six sites (infero-septal, antero-lateral, inferior,
      anterior, infero-lateral and antero-septal walls) at the basal region. IVC time
      (IVCT), IV relaxation time (IVRT), PS time (PSt), RR interval, mitral annulus
      motion (MAM), strain rate (SR), left ventricular filling pressure (E/E') and
      cardiac output were also measured. The average of the different walls was used to
      evaluate global function. Right ventricle (RV) dynamics was evaluated from
      measurements of IVC velocity (IVCv), peak systolic velocity (PSv), E' and A' from
      the RV free wall. RESULTS: No significant changes in cardiac output, IVCv, PSv,
      SR, MAM, E', A', E'/A', IVRT and LV filling pressure were observed, indicating
      that neither 40 mg (plus additional 40 mg after 30 min) nor 250 mg of furosemide
      had any measurable effects on LV filling pressure and LV and RV systolic and
      diastolic function. CONCLUSIONS: In anuric HD patients, low and high doses of
      furosemide had no significant effects on central cardiac haemodynamics.
      Therefore, the use of furosemide infusion in anuric ESRD patients with acute
      pulmonary oedema is not supported by the results of this study.

PMID- 18048422
TI  - Overexpression of PKD2 in the mouse is associated with renal tubulopathy.
AB  - Polycystin-2 (PC-2), a cation channel of the Trp family, is involved in autosomal
      dominant polycystic kidney disease (ADPKD) type 2 (ADPKD2). This protein has
      recently been localized to the primary cilium where its channel function seems to
      be involved in a mechanosensory phenomenon. However, its biological function is
      not totally understood, especially in tubule formation. In the present paper, we
      describe a mouse model for human PC-2 overexpression, obtained by inserting a
      human bacterial artificial chromosome (BAC) containing the PKD2 gene. Three lines
      were generated, expressing different levels of PKD2. One line, PKD2-Y, has been
      explored in more detail and we will present physiological and molecular
      exploration of these transgenic animals. Our data demonstrate that transgenic
      animals older than 12 months present tubulopathy with proteinuria and failure to
      concentrate urine. Moreover, the kidney cortex has been found disorganized.
      Finally, we observe that extracellular matrix protein expression is downregulated
      in these animals. In conclusion, overexpression of human PKD2 leads to anomalies
      in tubular function, probably due to abnormalities in tubule morphogenesis.

PMID- 18048423
TI  - Glomerular endothelium in kidneys with congenital nephrotic syndrome of the
      Finnish type (NPHS1).
AB  - BACKGROUND: The role of glomerular capillary endothelium in the pathophysiology
      of nephrotic kidney diseases is poorly known. We analysed the glomerular
      endothelial lesions in kidneys from patients with congenital nephrotic syndrome
      of the Finnish type (NPHS1). The disorder is caused by a genetic defect in a
      major podocyte slit diaphragm protein, nephrin. It manifests as nephrotic
      syndrome soon after birth and leads to glomerular sclerosis in early childhood.
      METHODS: The glomerular capillary and endothelial cell lesions in NPHS1 kidneys
      nephrectomized at infancy were studied by electron and light microscopy,
      immunohistochemistry and cytokine antibody array. RESULTS: Mesangial expansion
      and capillary obliteration were evident in practically all NPHS1 glomeruli. No
      thrombus formation was detected by fibrin staining. Electron microscopy revealed
      endothelial blebs (endotheliosis). The endothelial fenestration and the
      attachment of endothelial cells to the basement membrane were, however, quite
      normal. This fits to the abundant expression of a vascular endothelial growth
      factor (VEGF) and its transcription factor, hypoxia-inducible factor-1alpha (HIF
      1alpha), in NPHS1 glomer- uli. The proliferative activity of the intracapillary
      cells was modest and no apoptosis was detected. The expression of an endothelial
      adhesion molecule, intercellular adhesion molecule 1 (ICAM-1) and several
      chemokines was upregulated in NPHS1 glomeruli as compared to adult control
      kidneys. The recruitment of leukocytes carrying ligands for the major endothelial
      adhesion molecules, however, was modest in the mesangial area of NPHS1 glomeruli.
      CONCLUSIONS: The findings indicate that the glomerular endothelium is quite
      resistant to the nephrotic state in NPHS1 kidneys and underscores the importance
      of mesangial cells in the progression of glomerular sclerosis.

PMID- 18048425
TI  - Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and
      alleviates systemic and glomerular hypertension in experimental hyperuricaemia.
AB  - BACKGROUND: Experimentally-induced hyperuricaemia [due to inhibition of uricase
      with oxonic acid (OA)] in rats causes hypertension and renal alterations which
      can be prevented by lowering uric acid (UA) with allopurinol. Febuxostat (Fx), an
      investigational, nonpurine and selective xanthine oxidase inhibitor, is a more
      effective UA-lowering agent than allopurinol. We therefore tested the hypothesis
      that Fx might be useful in treating hyperuricemia-induced hypertension and renal
      damage. METHODS: Four groups of male rats were studied: OA (750 mg/kg by daily
      gavage) was given for 8 weeks and Fx (5-6 mg/kg/day in drinking water; OA+Fx: n =
      10) or placebo (OA+P: n = 11) were administered for 4 weeks beginning at 4 weeks
      after initiation of the study. Two groups of normal (N) rats were studied as
      controls (N+P and N+Fx: n = 10/group). Systolic blood pressure (SBP) and fasting
      plasma UA were measured in all animals at baseline and at 4 and 8 weeks.
      Glomerular haemodynamics by micropuncture techniques were determined at 8 weeks
      followed by histological evaluation of glomerular and afferent arteriole
      morphologies. RESULTS: In OA-induced hyperuricaemic rats, Fx lowered UA and
      ameliorated systemic and glomerular hypertension as well as mesangial matrix
      expansion and the development of preglomerular arteriolar disease as indicated by
      a reduction of the arteriolar area and media-to-lumen ratio. In normal rats, Fx
      tended to lower UA and had no effect on blood pressure, renal hemodynamics and
      afferent arteriole morphology. CONCLUSION: These results suggest that Fx merits
      further evaluation for the treatment of hypertension and renal alterations
      induced by hyperuricaemia.

PMID- 18048424
TI  - Guanidino compounds after creatine supplementation in renal failure patients and
      their relation to inflammatory status.
AB  - BACKGROUND: Specific guanidino compounds have been described as uraemic toxins
      and their concentrations are increased in renal failure due to dimished
      glomerular filtration, whereas the guanidino compound creatine is used as a
      performance-enhancing substance in athletes. The present study investigates the
      effects of creatine supplementation on plasma guanidino compounds in a chronic
      haemodialysis population. METHODS: Twenty male haemodialysis patients were
      included in a placebo-controlled cross-over trial. Patients were treated with
      creatine (2 g/day) or placebo during two treatment periods of 4 weeks, separated
      by a washout of 4 weeks. Plasma guanidino compounds and routine biochemical
      parameters were determined, as well as the prognostic inflammatory and
      nutritional index (PINI). RESULTS: Upon creatine supplementation,
      guanidinoacetate concentrations decreased by 15%, due to inhibition of creatine
      synthesis. Concentrations of alpha-keto-delta-guanidinovaleric acid increased
      three-fold and argininic acid concentrations doubled. Guanidinosuccinate
      concentrations did not change, but correlated inversely with CRP (r = -0.736; P =
      0.001), PINI-score (r = -0.716; P = 0.002) and correlated positively with plasma
      urea concentration (r = 0.54; P = 0.02). CONCLUSIONS: Creatine supplementation in
      haemodialysis patients significantly altered the concentration of specific
      guanidino compounds. Guanidinosuccinate correlated positively with plasma urea
      and negatively with inflammation markers.

PMID- 18048426
TI  - Off-the-shelf in-shoe heel inserts: does cost matter?
AB  - OBJECTIVE: A growing exercise culture has lead to an increase in the use of off
      the-shelf heel inserts. While there are a variety of designs in a spectrum of
      cost ranges, probably the ease of availability and cost would mainly determine
      the choice of purchase. This study was designed to determine whether expensive
      designs provide better pressure attenuation under the heel than their less
      expensive counterparts. PARTICIPANTS AND DESIGN: Six brands of off-the-shelf heel
      inserts were tested. Selection of these was based purely on their availability in
      all sizes. Cost per pair ranged from 6 pounds sterling to 30 pounds sterling.
      Thirty-five asymptomatic subjects walked on a 10 m walkway, once with no inserts
      and once with each pair of inserts. The Pedar in-shoe system recorded a range of
      parameters under the heel. SETTING: Institute of Motion Analysis and Research,
      Ninewells Hospital and Medical School, University of Dundee. MAIN OUTCOME
      MEASURES: Evaluation of plantar pressure parameters under the heel. RESULTS: All
      inserts reduced peak pressure under the heel. Maximum force and pressure-time
      integral also decreased. Contact time generally increased with the use of
      inserts. Values of contact area with and without inserts were comparable.
      CONCLUSIONS: No significant differences were observed under the heel between the
      pressure attenuation properties of the lowest-priced and the most expensive
      designs, and hence the less expensive inserts can be considered as good as the
      expensive brands. However, the endurance power of these inserts may differ and
      this should be evaluated.

PMID- 18048427
TI  - Osteoporotic fracture in an elite male Kenyan athlete.
AB  - An elite Kenyan runner presented with a tibial fracture sustained during an
      international cross-country race. There was no clear history of symptoms
      suggestive of preceding overload and no radiological features of stress fracture.
      He was found to have sustained an osteoporotic, insufficiency fracture. There are
      no previous case reports of an osteoporotic fracture in a male athlete. Possible
      aetiologies and directions for future investigation are presented.

PMID- 18048428
TI  - Injuries to junior club cricketers: the effect of helmet regulations.
AB  - OBJECTIVE: Despite the popularity of cricket at the junior community level, few
      studies have described injuries for this level of play. This study describes the
      epidemiology of cricket injuries in junior club cricket across three playing
      seasons to identify priorities for prevention. DESIGN: Prospective on-field
      injury data collection during match observation of acute injuries. Pre and post
      observational evaluation of mandatory helmet wearing. SETTING: The Sutherland
      Shire Junior Cricket Association, New South Wales, Australia during the 2002-03,
      2003-04 and 2004-05 playing seasons. PARTICIPANTS: All junior teams (Under 8 (U8)
      U16). INTERVENTION: Compulsory headgear introduced for all batters before the
      2004-05 season. MAIN OUTCOME MEASURES: Frequency of injury according to age
      level, grade of play and playing position, and injury rates per 100 registered
      players. RESULTS: 155 injuries were reported. No U8 player sustained an injury,
      and injury frequency increased with age. Traditional cricket was associated with
      more injuries than modified cricket. At each age level, the most skilled players
      had the lowest frequency of injury. Overall, batting accounted for 49% of all
      injuries and 29% occurred when fielding; contact with a moving ball was
      responsible for 55% of injuries. The most commonly injured body region was the
      face (20%), followed by the hand (14%). In batters, the frequency of
      head/neck/facial injuries fell from 62% in 2002/03 to 35% in 2003-04 to just 4%
      in 2004-05 after headgear use was compulsory. CONCLUSIONS: Injury rates in junior
      players are low, but increase with age and level of play. Use of protective
      headgear, particularly by batters, leads to a significant reduction in injuries.

PMID- 18048429
TI  - IOC consensus statement: "training the elite child athlete".

PMID- 18048430
TI  - Specific diving training-induced arterial circulation changes.
AB  - OBJECTIVE: Several stressors such as cold water immersion, hyperoxic exposure and
      decompression-induced circulating bubbles can alter arterial circulation after a
      dive. The aim of this study was to investigate the arterial modifications induced
      by a specific diving training including repeated hyperbaric exposures and
      physical training. METHOD: Arterial pressure measurement and pulse wave velocity
      (PWV) recordings were performed in 12 student military divers before and after 15
      weeks' training. The results were compared with the same investigations performed
      in 12 non-diver healthy subjects. RESULTS: A decrease in systolic blood pressure
      and pulse pressure was observed at both upper and lower limbs in student military
      divers after the training. Non-significant decreases in both carotido-femoral PWV
      and carotido-pedal PWV were found after the training. When the pulse time transit
      was divided by the cardiac cycle length between two R peaks ((RR) interval), a
      significant increase was observed between the carotid and femoral sensors. On the
      other hand, some differences were noticed between military divers and controls.
      Controls and divers were matched appropriately according to age and height,
      although the divers had a higher aerobic capacity as well as lower resting heart
      rate and lower pulse wave velocity. CONCLUSION: In trained military subjects, a
      training which includes repeated diving exposures and endurance exercises leads
      to vascular modifications suggesting an increase in central arterial compliance.
      There was no sign of arterial alteration induced by repeated diving exposures.

PMID- 18048431
TI  - Physiotherapists' use of information in identifying a concussion: an extended
      Delphi approach.
AB  - OBJECTIVE: To determine the relative importance of signs and symptoms that a
      selected cohort of sports physiotherapists use to identify a sports concussion.
      METHODS: A two-round Delphi methodology was used to achieve consensus in a cohort
      of 21 sports physiotherapists. A subsequent round involving an educational
      intervention provided the participants with an opportunity to modify their
      knowledge base through the provision of a relevant resource article. RESULTS:
      Participants provided 123 responses, which were grouped into eight descriptive
      categories with consensus (>80%) being reached for the importance of:
      cognition/orientation, memory, motor dysfunction and state of consciousness. The
      category "state of consciousness" remained the most important information source
      at the completion of the study. CONCLUSION: Participants placed considerable
      importance on the player's level of consciousness in their decision making. This
      would appear to be in conflict with recent trends to place greater importance on
      the role of symptoms in identifying a concussion.

PMID- 18048432
TI  - Decrease in body fat during an ultra-endurance triathlon is associated with race
      intensity.
AB  - OBJECTIVE: To investigate whether adipose subcutaneous tissue or skeletal muscle
      mass decreased during a non-stop ultra-endurance triathlon. DESIGN: Descriptive
      field study. SETTING: The Triple Iron Triathlon Germany 2006 in Lensahn: 11.6 km
      swimming, 540 km cycling and 126.6 km running. SUBJECTS: 17 male Caucasian
      triathletes, mean (SD) age 39.2 (7.5) years, height 178 (5) cm, body mass 80.7
      (8.9) kg and body mass index (BMI) 25.4 (2.4) kg/m(2). INTERVENTIONS: None. MAIN
      OUTCOME MEASUREMENTS: Determination of body mass, skin-fold thicknesses, limb
      circumference, skeletal muscle mass and percentage body fat in order to show
      changes after the race. RESULTS: A significant decrease was shown for body mass
      (p<0.001), BMI (p<0.001) and calculated percentage body fat (p<0.001) whereas
      skeletal muscle mass did not change significantly (p>0.05). Circumferences of the
      thigh, upper arm and calf did not decrease significantly (p>0.05), whereas all
      skin-fold thicknesses decreased significantly (p<0.05), with the exception of
      those at the chest and thigh. A significant correlation was found between the
      loss of percentage body fat and the loss of body mass (p<0.01, r(2) = 0.55) as
      well as change in percentage body fat with race performance (p<0.05, r(2) =
      0.24). CONCLUSIONS: Ultra-endurance triathletes at the Triple Iron Triathlon
      Germany 2006 showed a significant decrease in body mass and percentage body fat,
      where decrease in percentage body fat was associated with race intensity.

PMID- 18048433
TI  - Short-term glucocorticoid intake combined with intense training on performance
      and hormonal responses.
AB  - OBJECTIVE: To investigate the effects of short-term prednisolone ingestion
      combined with intense training on exercise performance, hormonal
      (adrenocorticotrophic hormone (ACTH), prolactin, luteinising hormone (LH), growth
      hormone (GH), thyroid-stimulating hormone (TSH), dehydroepiandrosterone (DHEA),
      testosterone, insulin) and metabolic parameters (blood glucose, lactate,
      bicarbonate, pH). METHODS: Eight male recreational athletes completed four
      cycling trials at 70-75% peak O(2) consumption until exhaustion just before (1)
      and after (2) either oral placebo or prednisolone (60 mg/day for 1 week)
      treatment coupled with standardised physical training (2 hours/day), according to
      a double-blind and randomised protocol. Blood samples were collected at rest,
      during exercise and passive recovery for the hormonal and metabolic
      determinations. RESULTS: Time of cycling was not significantly changed after
      placebo but significantly increased (p<0.05) after prednisolone administration
      (50.4 (6.2) min for placebo 1, 64.0 (9.1) min for placebo 2, 56.1 (9.1) min for
      prednisolone 1 and 107.0 (20.7) min for prednisolone 2). There was no significant
      difference in any measured parameters after the week of training with placebo but
      a decrease in ACTH, DHEA, PRL, GH, TSH and testosterone was seen with
      prednisolone treatment during the experiment (p<0.05). No significant change in
      basal, exercise or recovery LH, insulin, lactate, pH or bicarbonate was found
      between the two treatment, but blood glucose was significantly higher under
      prednisolone (p<0.05) at all time points. CONCLUSION: Short-term glucocorticoid
      administration induced a marked improvement in endurance performance. Further
      studies are needed to determine whether these results obtained in recreational
      male athletes maintaining a rigorous training schedule are gender-dependent and
      applicable to elite athletes.

PMID- 18048434
TI  - Autonomic and behavioural thermoregulation in tennis.
AB  - OBJECTIVES: This report describes physiological and behavioural mechanisms behind
      the control of body temperature and thermal comfort during competitive singles
      tennis. METHODS: Thermoregulatory responses and workload were observed during
      "best of three sets" tennis matches among 25 players. In total, 94 matches were
      played in ambient temperatures ranging from 14.5 to 38.4 degrees C. The thermal
      environment was assessed by dry bulb, wet bulb and natural wet bulb temperatures,
      globe temperature and wind speed. Core body and skin temperatures were recorded
      each minute throughout the match, and body mass and fluid intake were measured
      before the match, after 30 minutes of play and at the completion of the match to
      determine sweat rate. Subjective ratings of thermal strain included thermal
      comfort, sweatiness and perceived exertion. Workload observations included match,
      game and point durations, and the proportion of match time spent in play
      (effective playing time). RESULTS: Change in rectal temperature was positively
      correlated with point duration (p<0.001) and effective playing time (p<0.05).
      Sweat rate showed positive associations with air (p<0.0001), rectal (p<0.03) and
      skin (p<0.0001) temperature. Thermal comfort was reduced with increasing rectal
      (p<0.03) and skin (p<0.0001) temperature. Point duration and effective playing
      time were reduced when conditions were rated increasingly difficult (p<0.002 and
      p<0.0002, respectively). CONCLUSION: Autonomic (increase in sweat rate) and
      behavioural (reduction in workload) thermoregulation are responsible for the
      control of body temperature and thermal comfort during tennis.

PMID- 18048435
TI  - Effect of Ganoderma lucidum capsules on T lymphocyte subsets in football players
      on "living high-training low".
AB  - OBJECTIVE: G lucidum is a popular Chinese herb with an impressive array of
      reputed health benefits. The purpose of this study was to provide information
      related to the modulating effect of G lucidum capsules on T lymphocyte subsets in
      football players during a 28-day "living high-training low "(LHTL) trial and
      their possible mechanism of action. METHODS: Forty male football players were
      randomly assigned to four groups: control (living at sea level), LHTL1, LHTL2 and
      LHTL3. The three LHTL groups had stayed in normobaric hypoxic rooms for 28 days.
      The four groups trained together at sea level. LHTL1, LHTL2 and LHTL3 groups were
      provided with placebo, G lucidum 10 capsules/day and G lucidum 20 capsules/day,
      respectively, for 6 weeks (2 weeks baseline supplementation followed by 28 days
      of the treatment protocol). Lymphocyte subsets were quantitated using flow
      cytometry. RESULTS: In the LHTL1 group, when the CD4+/CD8+ ratio was expressed as
      relative changes from the baseline, a significant decrease was seen following the
      28-day trial compared to the baseline. Furthermore, a significant decrease was
      observed between LHTL1 and control groups at 21 days. In the LHTL2 group, the
      relative change of CD4+/CD8+ ratio from the baseline was significantly lower at
      28 days compared with the pretrial baseline. Generally, in the LHTL3 group there
      was a trend for the per cent changes of the CD4+/CD8+ ratio from thebaseline to
      be higher than the values for the LHTL1 andLHTL2 groups, but this was not
      significant. CONCLUSION: LHTL could affect T lymphocyte subsets significantly as
      a result of the two simultaneous stimuli of physical activity and exposure to
      hypoxia. The ingestion of G lucidum in the LHTL3 group could help to ameliorate
      the variation of the CD4+/CD8+ ratio in LHTL training, and polysaccharides from G
      lucidum might be the main active components for the cell-mediated immune
      function.

PMID- 18048436
TI  - Energy expenditure during a single-handed transatlantic yacht race.
AB  - BACKGROUND: The popularity of sports that expose people to consecutive days of
      high-intensity physical activity continues to increase. The ability to adequately
      nourish the human body to sustain the required level of competitive performance
      may be a key contributor to success in such events. METHODS: The energy
      expenditure of a male competitor in a single-handed, transatlantic race (Transat
      2004) was assessed using the doubly-labelled water technique. RESULTS: Mean total
      daily energy expenditure (TDEE) during the race (13 days) was 14.5 MJ/day with a
      peak expenditure of 18.6 MJ during the most physically demanding 24-hour period.
      DISCUSSION: This mean TDEE was approximately 25% lower than that reported in a
      previous study (14.5 vs. 19.3 MJ/day) for a 13-day leg of a fully crewed offshore
      race. The difference in results was probably due to the fact that in the previous
      study, the crew operated in "watches" (work shifts), affording each crew member
      greater opportunity to eat, rest and sleep. Effective planning and efficient
      management of resources is essential to the success of the solo sailor. However,
      the extent to which maintenance of energy balance underpins competitive success
      remains to be established. To maintain energy balance during the race, a mean
      daily energy intake of 14.5 MJ/day was necessary for the subject in this study.
      However, this mean value for energy intake would have been inadequate to match
      the peak energy expended during the most physically demanding 24 hours of the
      race.

PMID- 18048437
TI  - Joint loading modality: its application to bone formation and fracture healing.
AB  - Sports-related injuries such as impact and stress fractures often require a
      rehabilitation programme to stimulate bone formation and accelerate fracture
      healing. This review introduces a recently developed joint loading modality and
      evaluates its potential applications to bone formation and fracture healing in
      post-injury rehabilitation. Bone is a dynamic tissue whose structure is
      constantly altered in response to its mechanical environments. Indeed, many
      loading modalities can influence the bone remodelling process. The joint loading
      modality is, however, able to enhance anabolic responses and accelerate wound
      healing without inducing significant in situ strain at the site of bone formation
      or fracture healing. This review highlights the unique features of this loading
      modality and discusses its potential underlying mechanisms as well as possible
      clinical applications.

PMID- 18048438
TI  - Injury rate and socioeconomic costs resulting from sports injuries in Flanders:
      data derived from sports insurance statistics 2003.
AB  - OBJECTIVE: This study determines the injury rate (%) and the associated direct
      medical and indirect costs of sports injuries in Flanders. SETTING:
      Epidemiological cohort designs and a human capital method were set up to measure
      respectively the medical direct and indirect cost of sports injuries.
      PARTICIPANTS: 72 out of 82 Flemish sports federations participated. INTERVENTION:
      Insurance statistics from 2003 were used to determine the overall rate of injury
      and injury localisations. Using these data, the medical direct cost and the
      impact sports injuries have on indirect costs were estimated. The indirect costs
      were determined by multiplying the days of absence from work with the daily cost
      resulting from a loss of production, being 200 euros. MAIN OUTCOME: The total
      direct medical cost extrapolated for the Flemish sports participants was
      15,027,423 euros, which amounted to 0.07% to 0.08% of the total budget spent on
      healthcare. The indirect cost extrapolated for the Flemish sports participants
      was 111,420,813 euros, which is about 3.4% of the costs arising from absenteeism
      from work. RESULTS: Of the 14 in-depth analysed sports, the rate of injury was
      highest in European team handball (8.96%; 95% confidence interval (CI) 8.95-8.96)
      and lowest in swimming (0.62%; 95% CI 0.62-0.62). The highest direct medical cost
      was found for anterior cruciate ligament (ACL) injuries (1358 euros per injury)
      and the lowest for foot injuries (52 euros per injury). CONCLUSION: The costs
      calculated in this study could become critical statistics in medical care
      debates. Data obtained here will enable a cost-benefit analysis of the impact of
      preventive measures to be made.

PMID- 18048439
TI  - Evaluating SafeClub: can risk management training improve the safety activities
      of community soccer clubs?
AB  - OBJECTIVE: To evaluate a sports safety-focused risk-management training
      programme. DESIGN: Controlled before and after test. SETTING: Four community
      soccer associations in Sydney, Australia. PARTICIPANTS: 76 clubs (32
      intervention, 44 control) at baseline, and 67 clubs (27 intervention, 40 control)
      at post-season and 12-month follow-ups. INTERVENTION: SafeClub, a sports safety
      focused risk-management training programme (3x2 hour sessions) based on adult
      learning principles and injury-prevention concepts and models. MAIN OUTCOME
      MEASURES: Changes in mean policy, infrastructure and overall safety scores as
      measured using a modified version of the Sports Safety Audit Tool. RESULTS: There
      was no significant difference in the mean policy, infrastructure and overall
      safety scores of intervention and control clubs at baseline. Intervention clubs
      achieved higher post-season mean policy (11.9 intervention vs 7.5 controls),
      infrastructure (15.2 vs 10.3) and overall safety (27.0 vs 17.8) scores than did
      controls. These differences were greater at the 12-month follow-up: policy (16.4
      vs 7.6); infrastructure (24.7 vs 10.7); and overall safety (41.1 vs 18.3).
      General linear modelling indicated that intervention clubs achieved statistically
      significantly higher policy (p<0.001), infrastructure (p<0.001) and overall
      safety (p<0.001) scores compared with control clubs at the post-season and 12
      month follow-ups. There was also a significant linear interaction of time and
      group for all three scores: policy (p<0.001), infrastructure (p<0.001) and
      overall safety (p<0.001). CONCLUSIONS: SafeClub effectively assisted community
      soccer clubs to improve their sports safety activities, particularly the
      foundations and processes for good risk-management practice, in a sustainable
      way.

PMID- 18048440
TI  - Running performance, not anthropometric factors, is associated with race success
      in a Triple Iron Triathlon.
AB  - OBJECTIVES: To investigate the influence of anthropometric parameters on race
      performance in ultra-endurance triathletes. DESIGN: Descriptive field study.
      SETTING: The Triple Iron Triathlon Germany 2006 in Lensahn over 11.6 km swimming,
      540 km cycling and 126.6 km running. SUBJECTS: 17 male Caucasian triathletes
      (mean (SD) 39.2 (7.5) years, 80.7 (8.9) kg, 178 (5) cm, BMI 25.4 (2.4) kg/m(2)).
      INTERVENTIONS: None. MAIN OUTCOME MEASUREMENTS: Determination of body mass, body
      height, skin fold thicknesses, circumferences of extremities, as well as
      calculation of body mass index (BMI), skeletal muscle mass (SM), per cent SM
      (%SM) and per cent body fat (%BF) in order to correlate measured and calculated
      anthropometric parameters with race performance. RESULTS: Body mass, body height,
      skin fold thicknesses, circumferences of extremities, BMI, %SM and %BF had no
      effect (p>0.05) on race performance. No significant correlation (p>0.05) was
      observed between total race time and any of the directly measured and calculated
      anthropometric properties. A significant correlation (p<0.05) was observed
      between total race time and both running time (r(2) = 0.87) and cycling time
      (r(2) = 0.62). In contrast, no significant correlation (p>0.05) was shown between
      swimming time and total race time. CONCLUSIONS: There is no significant
      association between anthropometric parameters and race performance in ultra
      endurance triathletes. Running performance rather than cycling performance seems
      to be the most important factor in order to be successful in a Triple Iron
      Triathlon. Swimming performance seems to be of low importance.

PMID- 18048441
TI  - Walking and primary prevention: a meta-analysis of prospective cohort studies.
AB  - OBJECTIVE: To quantify the association between walking and the risk of
      cardiovascular disease (CVD) and all-cause mortality in healthy men and women.
      DATA SOURCES: Medline, Cochrane Database of Systematic Reviews, and Web of
      Science databases were searched to May 2007. STUDY SELECTION: Prospective
      epidemiological studies of walking and CVD and all-cause mortality. RESULTS: 18
      prospective studies were included in the overall analysis, which incorporated 459
      833 participants free from CVD at baseline with 19 249 cases at follow-up. From
      the meta-analysis the pooled hazard ratio of CVD in the highest walking category
      compared with the lowest was 0.69, (95% CI 0.61 to 0.77, p<0.001), and 0.68 (0.59
      to 0.78, p<0.001) for all-cause mortality. These effects were robust among men
      and women, although there was evidence of publication biases for the associations
      with CVD risk. Walking pace was a stronger independent predictor of overall risk
      compared with walking volume (48% versus 26% risk reductions, respectively).
      There was also evidence of a dose-response relationship across the highest,
      intermediate, and lowest walking categories in relation to the outcome measures.
      CONCLUSIONS: The results suggest walking is inversely associated with clinical
      disease endpoints and largely support the current guidelines for physical
      activity. The mechanisms that mediate this relationship remain largely unknown
      and should be the focus of future research.

PMID- 18048442
TI  - The relationship between changes in interstitial creatine kinase and game-related
      impacts in rugby union.
AB  - AIM: The primary purpose of this study was to investigate the relationship
      between the pre-game to post-game changes in creatine kinase concentration
      (Delta[CK]) and impact-related game statistics in elite rugby union players.
      METHODS: Twenty-three elite male rugby union players each provided interstitial
      fluid samples obtained via electrosonophoresis (ESoP) 210 min before and within a
      maximum time of 30 min after up to five rugby union games. Specific game
      statistics that were deemed to be important in determining the relationship
      between impact and [CK] were obtained from AnalyRugby software for each
      individual player. Regression equations to predict Delta[CK] from game statistics
      were created using a backwards random-effects maximum likelihood regression.
      RESULTS: The Delta[CK] (mean (SD)) from pre-game to post-game was 926.8 (204.2)
      IU. Game time and time defending were significantly correlated to Delta[CK] in
      both the forwards and backs. The predicted Delta[CK] (mean (95% confidence
      limit)) was 1439.8 (204.9) IU for the forwards and 545.3 (78.0) IU for the backs
      and was significantly correlated with the actual Delta[CK] (r = 0.69 and r =
      0.74). CONCLUSIONS: CK increased from pre-game to post-game in a position
      specific manner. A large proportion of the Delta[CK] can be explained by physical
      impact and thus can be predicted using a prescribed number of game statistics. As
      the Delta[CK] is an indicator of muscle damage, the prediction of Delta[CK]
      provides a theoretical basis for recovery strategies and adjustment of subsequent
      training sessions after rugby union games.

PMID- 18048443
TI  - Thermoregulatory responses during competitive singles tennis.
AB  - OBJECTIVES: To provide examples of thermoregulatory responses during competitive
      singles tennis and comparisons with continuous, steady-state running. METHODS:
      Typical examples of body core (rectal) temperature, skin temperature and heart
      rate were selected to show the differing characteristics of tennis and running,
      and the corresponding thermal environments. Rectal and skin temperatures were
      logged each minute and heart rate logged every 15 seconds throughout the
      competitive "best of three sets" singles tennis matches and 60-minute continuous,
      steady-state running trials. Tennis matches were completed outdoors in widely
      varying thermal environments, and the running trials were completed in the
      laboratory under stable conditions. RESULTS: Rectal temperature in tennis was
      raised only slightly above resting levels, reaching a plateau relative to the
      exercise intensity. Rectal temperature during tennis was found to take longer to
      reach a plateau than continuous, steady-state exercise. Skin temperature during
      tennis varied widely depending on environmental air temperature, and was lower
      than that of runners at the same air temperature. Heart rate was very similar
      between opponents for both average and response characteristics during tennis. A
      wider range and higher peak values were found for tennis players compared with
      runners. CONCLUSIONS: This report provides a descriptive account of
      thermoregulatory response characteristics during singles tennis. Differences
      between outdoor tennis and continuous, steady-state running in the laboratory for
      each of these responses were found.

PMID- 18048444
TI  - Isolated proximal tibiofibular joint dislocation in an elite rugby union player.
AB  - The case is presented of a professional international rugby union player who
      sustained an isolated proximal tibiofibular dislocation in a training ground
      injury. Diagnosis was made based on clinical details, plain radiography and
      magnetic resonance imaging. An initial attempt at closed reduction failed. Open
      reduction and internal fixation were subsequently carried out. Following early
      rehabilitation, the patient made a successful try-scoring return to international
      rugby union.

PMID- 18048445
TI  - The key to top-level endurance running performance: a unique example.

PMID- 18048447
TI  - An Il-lumen-ating look at ryanodine receptor modulation by disruption in triadin
      and calsequestrin interactions in cardiac myocytes.

PMID- 18048446
TI  - Imaging of opioid receptors in the central nervous system.
AB  - In vivo functional imaging by means of positron emission tomography (PET) is the
      sole method for providing a quantitative measurement of mu-, kappa and delta
      opioid receptor-mediated signalling in the central nervous system. During the
      last two decades, measurements of changes to the regional brain opioidergic
      neuronal activation--mediated by endogenously produced opioid peptides, or
      exogenously administered opioid drugs--have been conducted in numerous chronic
      pain conditions, in epilepsy, as well as by stimulant- and opioidergic drugs.
      Although several PET-tracers have been used clinically for depiction and
      quantification of the opioid receptors changes, the underlying mechanisms for
      regulation of changes to the availability of opioid receptors are still unclear.
      After a presentation of the general signalling mechanisms of the opioid receptor
      system relevant for PET, a critical survey of the pharmacological properties of
      some currently available PET-tracers is presented. Clinical studies performed
      with different PET ligands are also reviewed and the compound-dependent findings
      are summarized. An outlook is given concluding with the tailoring of tracer
      properties, in order to facilitate for a selective addressment of dynamic changes
      to the availability of a single subclass, in combination with an optimization of
      the quantification framework are essentials for further progress in the field of
      in vivo opioid receptor imaging.

PMID- 18048448
TI  - Spike timing-dependent plasticity: a learning rule for dendritic integration in
      rat CA1 pyramidal neurons.
AB  - Long-term plasticity of dendritic integration is induced in parallel with long
      term potentiation (LTP) or depression (LTD) based on presynaptic activity
      patterns. It is, however, not clear whether synaptic plasticity induced by
      temporal pairing of pre- and postsynaptic activity is also associated with
      synergistic modification in dendritic integration. We show here that the spike
      timing-dependent plasticity (STDP) rule accounts for long-term changes in
      dendritic integration in CA1 pyramidal neurons in vitro. Positively correlated
      pre- and postsynaptic activity (delay: +5/+50 ms) induced LTP and facilitated
      dendritic integration. Negatively correlated activity (delay: -5/-50 ms) induced
      LTD and depressed dendritic integration. These changes were not observed
      following positive or negative pairing with long delays (> +/-50 ms) or when NMDA
      receptors were blocked. The amplitude-slope relation of the EPSP was facilitated
      after LTP and depressed after LTD. These effects could be mimicked by voltage
      gated channel blockers, suggesting that the induced changes in EPSP waveform
      involve the regulation of voltage-gated channel activity. Importantly, amplitude
      slope changes induced by STDP were found to be input specific, indicating that
      the underlying changes in excitability are restricted to a limited portion of the
      dendrites. We conclude that STDP is a common learning rule for long-term
      plasticity of both synaptic transmission and dendritic integration, thus
      constituting a form of functional redundancy that insures significant changes in
      the neuronal output when synaptic plasticity is induced.

PMID- 18048449
TI  - Functional role of cyclic nucleotide-gated channels in rat medial vestibular
      nucleus neurons.
AB  - Although cyclic nucleotide-gated (CNG) channels are expressed in numerous brain
      areas, little information is available on their functions in CNS neurons. The aim
      of the present study was to define the distribution of CNG channels in the rat
      medial vestibular nucleus (MVN) and their possible involvement in regulating MVN
      neuron (MVNn) excitability. The majority of MVNn expressed both CNG1 and CNG2 A
      subunits. In whole-cell current-clamp experiments carried out on brainstem slices
      containing the MVNn, the membrane-permeant analogues of cyclic nucleotides, 8-Br
      cGMP and 8-Br-cAMP (1 mM), induced membrane depolarizations (8.9 +/- 0.8 and 9.2
      +/- 1.0 mV, respectively) that were protein kinase independent. The cGMP-induced
      depolarization was associated with a significant decrease in the membrane input
      resistance. The effects of cGMP on membrane potential were almost completely
      abolished by the CNG channel blockers, Cd(2+) and L-cis-diltiazem, but they were
      unaffected by blockade of hyperpolarization-activated cyclic nucleotide-gated
      channels. In voltage-clamp experiments, 8-Br-cGMP induced non-inactivating inward
      currents (-22.2 +/- 3.9 pA) with an estimated reversal potential near 0 mV, which
      were markedly inhibited by reduction of extracellular Na(+) and Ca(2+)
      concentrations. Membrane depolarization induced by CNG channel activation
      increased the firing rate of MVNn without changing the action potential shape.
      Collectively, these findings provide novel evidence that CNG channels affect
      membrane potential and excitability of MVNn. Such action should have a
      significant impact on the function of these neurons in sensory-motor integration
      processes. More generally, it might represent a broad mechanism for regulating
      the excitability of different CNS neurons.

PMID- 18048450
TI  - The KCNQ/M-current modulates arterial baroreceptor function at the sensory
      terminal in rats.
AB  - The ion channels responsible for the pattern and frequency of discharge in
      arterial baroreceptor terminals are, with few exceptions, unknown. In this study
      we examined the contribution of KCNQ potassium channels that underlie the M
      current to the function of the arterial baroreceptors. Labelled aortic
      baroreceptor neurons, immunohistochemistry and an isolated aortic arch
      preparation were used to demonstrate the presence and function of KCNQ2, KCNQ3
      and KCNQ5 channels in aortic baroreceptors. An activator (retigabine) and an
      inhibitor (XE991) of the M-current were used to establish a role for these
      channels in setting the resting membrane potential and in regulating the response
      to ramp increases in arterial pressure. Retigabine raised the threshold for
      activation of arterial baroreceptors and shifted the pressure-response curve to
      higher aortic pressures. XE991, on the other hand, produced an increase in
      excitability as shown by an increase in discharge at elevated pressures as
      compared to control. We propose that KCNQ2, KCNQ3 and KCNQ5 channels provide a
      hyperpolarizing influence to offset the previously described depolarizing
      influence of the HCN channels in baroreceptor neurons and their terminals.

PMID- 18048451
TI  - Neuronal nitric oxide synthase control mechanisms in the cutaneous vasculature of
      humans in vivo.
AB  - The physiological roles of constitutively expressed nitric oxide synthase (NOS)
      isoforms in humans, in vivo, are unknown. Cutaneous vasodilatation during both
      central nervous system-mediated, thermoregulatory reflex responses to whole-body
      heat stress and during peripheral axon reflex-mediated, local responses to skin
      warming in humans depend on nitric oxide (NO) generation by constitutively
      expressed NOS of uncertain isoform. We hypothesized that neuronal NOS (nNOS, NOS
      I) effects cutaneous vasodilatation during whole-body heat stress, but not during
      local skin warming. We examined the effects of the nNOS inhibitor 7-nitroindazole
      (7-NI) administered by intradermal microdialysis on vasodilatation induced by
      whole-body heat stress or local skin warming. Skin blood flow (SkBF) was
      monitored by laser-Doppler flowmetry (LDF). Blood pressure (MAP) was monitored
      and cutaneous vascular conductance calculated (CVC = LDF/MAP). In protocol 1,
      whole-body heat stress was induced with water-perfused suits. In protocol 2,
      local skin warming was induced through local warming units at LDF sites. At the
      end of each protocol, 56 mm sodium nitroprusside was perfused at microdialysis
      sites to raise SkBF to maximal levels for data normalization. 7-NI significantly
      attenuated CVC increases during whole-body heat stress (P < 0.05), but had no
      effect on CVC increases induced by local skin warming (P > 0.05). These
      diametrically opposite effects of 7-NI on two NO-dependent processes verify
      selective nNOS antagonism, thus proving that the nNOS isoform affects NO
      increases and hence vasodilatation during centrally mediated, reflex responses to
      whole-body heat stress, but not during locally mediated, axon reflex responses to
      local skin warming. We conclude that the constitutively expressed nNOS isoform
      has distinct physiological roles in cardiovascular control mechanisms in humans,
      in vivo.

PMID- 18048452
TI  - Exercise intensity-dependent contribution of beta-adrenergic receptor-mediated
      vasodilatation in hypoxic humans.
AB  - We previously reported that hypoxia-mediated reductions in alpha-adrenoceptor
      sensitivity do not explain the augmented vasodilatation during hypoxic exercise,
      suggesting an enhanced vasodilator signal. We hypothesized that beta-adrenoceptor
      activation contributes to augmented hypoxic exercise vasodilatation. Fourteen
      subjects (age: 29 +/- 2 years) breathed hypoxic gas to titrate arterial O(2)
      saturation (pulse oximetry) to 80%, while remaining normocapnic via a rebreath
      system. Brachial artery and antecubital vein catheters were placed in the
      exercising arm. Under normoxic and hypoxic conditions, baseline and incremental
      forearm exercise (10% and 20% of maximum) was performed during control (saline),
      alpha-adrenoceptor inhibition (phentolamine), and combined alpha- and beta
      adrenoceptor inhibition (phentolomine/propranolol). Forearm blood flow (FBF),
      heart rate, blood pressure, minute ventilation, and end-tidal CO(2) were
      determined. Hypoxia increased heart rate (P < 0.05) and minute ventilation (P <
      0.05) at rest and exercise under all drug infusions, whereas mean arterial
      pressure was unchanged. Arterial adrenaline (P < 0.05) and venous noradrenaline
      (P < 0.05) were higher with hypoxia during all drug infusions. The change (Delta)
      in FBF during 10% hypoxic exercise was greater with phentolamine (Delta306 +/- 43
      ml min(-1)) vs. saline (Delta169 +/- 30 ml min(-1)) or combined
      phentolamine/propranolol (Delta213 +/- 25 ml min(-1); P < 0.05 for both). During
      20% hypoxic exercise, DeltaFBF was greater with phentalomine (Delta466 +/- 57 ml
      min(-1); P < 0.05) vs. saline (Delta346 +/- 40 ml min(-1)) but was similar to
      combined phentolamine/propranolol (Delta450 +/- 43 ml min(-1)). Thus, in the
      absence of overlying vasoconstriction, the contribution of beta-adrenergic
      mechanisms to the augmented hypoxic vasodilatation is dependent on exercise
      intensity.

PMID- 18048455
TI  - Under microscopes the poly(styrene/butadiene) nanoparticles.
AB  - There has been considerable interest, both academic and industrial, in developing
      synthesis processes for making polymeric nanoparticles. Our effort relied on the
      nanoassembly concepts of block macromolecules in solutions to prepare particles
      with a hard core made of crosslinked plastics and a soft shell made of low T(g)
      elastomer. By a suitable variation of the composition, polymer molecular weight
      and solute concentration, we were able to produce spherical, ellipsoidal,
      cylindrical, and chain-like nanoparticles. Under microscopes, the chain-like
      nanoparticles displayed very rich conformational features in diluted and dense
      states. Our observation on the conformation characters of the nanochains in 3D
      diluted state agreed well with the proposition of the self-avoid coil model.
      However, in 2D dense state, our observation on the nanochains appeared to be in
      contradiction with the segregated globule model proposed by de Gennes.

PMID- 18048454
TI  - Apical SK potassium channels and Ca2+-dependent anion secretion in endometrial
      epithelial cells.
AB  - Apical uridine triphosphate (UTP) stimulation was shown to increase short circuit
      current (I(sc)) in immortalized porcine endometrial gland epithelial monolayers.
      Pretreatment with the bee venom toxin apamin enhanced this response. Voltage
      clamp experiments using amphotericin B-permeablized monolayers revealed that the
      apamin-sensitive current increased immediately after UTP stimulation and was K(+)
      dependent. The current-voltage relationship was slightly inwardly rectifying with
      a reversal potential of -52 +/- 2 mV, and the P(K)/P(Na) ratio was 14, indicating
      high selectivity for K(+). Concentration-response relationships for apamin and
      dequalinium had IC(50) values of 0.5 nm and 1.8 microm, respectively, consistent
      with data previously reported for SK3 channels in excitable cells and
      hepatocytes. Treatment of monolayers with 50 microm BAPTA-AM completely blocked
      the effects of UTP on K(+) channel activation, indicating that the apamin
      sensitive current was also Ca(2+) dependent. Moreover, channel activation was
      blocked by calmidazolium (IC(50) = 5 microm), suggesting a role for calmodulin in
      Ca(2+)-dependent regulation of channel activity. RT-PCR experiments demonstrated
      expression of mRNA for the SK1 and SK3 channels, but not SK2 channels. Treatment
      of monolayers with 20 nm oestradiol-17beta produced a 2-fold increase in SK3
      mRNA, a 2-fold decrease in SK1 mRNA, but no change in GAPDH mRNA expression. This
      result correlated with a 2.5-fold increase in apamin-sensitive K(+) channel
      activity in the apical membrane. We speculate that SK channels provide a
      mechanism for rapidly sensing changes in intracellular Ca(2+) near the apical
      membrane, evoking immediate hyperpolarization necessary for increasing the
      driving force for anion efflux following P2Y receptor activation.

PMID- 18048453
TI  - Zinc inhibition of rat NR1/NR2A N-methyl-D-aspartate receptors.
AB  - Zinc ions (Zn(2+)) are localized in presynaptic vesicles at glutamatergic
      synapses and released in an activity-dependent manner. Modulation of NMDA-type
      glutamate receptors by extracellular Zn(2+) may play an important role under
      physiological conditions and during pathologies such as ischaemia or seizure.
      Zn(2+) inhibits NMDA receptors containing the NR2A subunit with an IC(50) value
      in the low nanomolar concentration range. Here we investigate at the single
      channel level the mechanism of high affinity Zn(2+) inhibition of recombinant
      NR1/NR2A receptors expressed in HEK293 cells. Zn(2+) reversibly decreases the
      mean single-channel open duration and channel open probability determined in
      excised outside-out patches, but has no effect on single-channel current
      amplitude. A parallel series of experiments demonstrates that lowering
      extracellular pH (increasing proton concentration) has a similar effect on
      NR1/NR2A single-channel properties as Zn(2+). Fitting the sequence of single
      channel events with kinetic models suggests that the association of Zn(2+) with
      its binding site enhances proton binding. Modelling further suggests that
      protonated channels are capable of opening but with a lower open probability than
      unprotonated channels. These data and analyses are consistent with Zn(2+)
      mediated inhibition of NMDA receptors primarily reflecting enhancement of proton
      inhibition.

PMID- 18048456
TI  - Small clusters of granule-containing cells at the lateral side of the posterior
      cricoarytenoid muscle of the young adult rat.
AB  - Small clusters consisting of granule-containing cells, sustentacular cells and
      capillaries around them, similar in structure to the carotid body-like
      paraganglia, sometimes existed at the lateral side of the posterior
      cricoarytenoid (PCA) muscle of young adult (3 months) rats. Differing from the
      paraganglia, however, these cell clusters were discontinuously invested by
      slender cytoplasmic processes of fibroblasts. In individual granule-containing
      cells, granules varied in size and had a concentrically or eccentrically
      arranged, electron-dense material, resembling those of chromaffin cells of the
      adrenal medulla. A series of desmosome-like structures were frequently observed
      between adjacent granule-containing cells, but synapses between them were not
      necessarily clear. Nerve endings containing clear synaptic vesicles and
      occasional granulated vesicles, being possibly cholinergic in nature, sometimes
      formed synapses with the granule-containing cells, probably indicating that the
      granule-containing cells receive the efferent nerve innervation. On the other
      hand, the sustentacular cells lacked cytoplasmic granules and sent their
      cytoplasmic processes around the granule-containing cells. Capillaries in and
      around clustered cells were of the fenestrated type. From these findings, it is
      suggested that unlike the carotid body-like paraganglia, the noncapsulated cell
      clusters at the lateral side of the PCA muscle of the young adult rat may be
      identical to groups of extra-adrenal chromaffin tissues.

PMID- 18048457
TI  - Gene expression profile in labouring and non-labouring human placenta near term.
AB  - The duration of pregnancy and initiation of labour are thought to be controlled
      by fetal, maternal and placental factors. The aim of this study was to
      investigate whether labour influences gene expression in placenta near term.
      Placental samples were obtained from 27 women after vaginal delivery (labouring)
      and 17 women after elective Caesarean section (non-labouring). All women were
      Caucasian and had uncomplicated pregnancies. For global gene expression analysis,
      17 human oligo-arrays were used, representing 24 650 genes each. An empirical
      Bayes analysis was applied in order to find differentially expressed genes. About
      8000 genes that were represented on the arrays met our quality criteria. Ninety
      two genes were down-regulated and 94 genes were up-regulated in labouring
      placentas compared to non-labouring placentas. However, none of these was
      differentially expressed at a significant level (>2.5-fold change and a P-value
      of <0.01). We conclude that gene expression in near term human placenta is not
      significantly altered by labour.

PMID- 18048458
TI  - Fine-scale quantification of HCG beta gene transcription in human trophoblastic
      and non-malignant non-trophoblastic tissues.
AB  - Human chorionic gonadotropin (HCG) is produced by syncytiotrophoblast of
      placenta. It delays the apoptosis of corpus luteum and functions in implantation.
      Its possible role in male reproduction has been raised. HCG beta subunit is
      encoded by CGB, CGB5, CGB7 and CGB8 genes located at 19q13.3 in a common genome
      cluster with beta subunit non-coding CGB1 and CGB2. We conducted a sensitive
      quantification and comparison of CGB gene expression in human trophoblastic
      (blastocysts, n = 6; normal/failed pregnancy, n = 51) and non-malignant non
      trophoblastic tissues (15 different tissue types, samples n = 241), by real-time
      RT-PCR. We showed a wide transcriptional window of CGB genes in normal pregnancy,
      a significant reduction in recurrent miscarriages, and a high expression
      (especially CGB1/CGB2) in ectopic and molar pregnancies. Expression was several
      orders of magnitude lower in the non-placental tissues, with the highest CGB
      levels being seen in testis, prostate, thymus, skeletal muscle and lung samples.
      The contribution of CGB1/CGB2 to the summarized expression of six CGB genes was
      not proportional to their gene dosage: 1/1000 to 1/10,000. An interesting
      exception was the testis exhibiting a much higher CGB1/CGB2 to total CGB mRNA
      ratio of approximately one-third, corresponding to gene dosage. In conclusion,
      the expressional profile of CGB genes, activated already in blastocyst stage, is
      associated with the status of pregnancy. The presence of CGB transcripts in
      testes, and in particular CGB1/CGB2 transcripts, may indicate a role in male
      reproductive tract.

PMID- 18048459
TI  - Hormone control and expression of androgen receptor coregulator MAGE-11 in human
      endometrium during the window of receptivity to embryo implantation.
AB  - The androgen receptor (AR) is a ligand-activated transcription factor of the male
      and female reproductive tracts whose activity is modulated by coregulator
      binding. We recently identified melanoma antigen gene protein-11 (MAGE-11) of the
      MAGEA gene family that functions as an AR coregulator by binding the AR N
      terminal FXXLF motif. Here we report that MAGE-11 is expressed in a temporal
      fashion in endometrium of normally cycling women. Highest levels of MAGE-11 mRNA
      and protein occur in the mid-secretory stage, coincident with the window of
      uterine receptivity to embryo implantation. Studies in human endometrial cell
      lines together with the hormone profile of the menstrual cycle and pattern of
      estrogen receptor-alpha expression in cycling endometrium suggest the rise in
      MAGE-11 mRNA results from down-regulation by estradiol during the proliferative
      phase and up-regulation by cyclic AMP signaling in the early and mid-secretory
      stage. In agreement with its coregulatory function, MAGE-11 localizes with AR in
      glandular epithelial cell nuclei in the mid-secretory stage. The increase in AR
      protein in the mid-secretory endometrium without an increase in AR mRNA suggests
      MAGE-11 stabilizes AR in glandular epithelial cell nuclei. This was supported by
      expression studies at low androgen levels indicating AR stabilization by MAGE-11
      dependent on the AR N-terminal transactivation domain. The results suggest that
      MAGE-11 functions as a coregulator that increases AR transcriptional activity
      during the establishment of uterine receptivity in the human female.

PMID- 18048460
TI  - Intravenous magnesium sulphate vs. inhaled nitric oxide for moderate, persistent
      pulmonary hypertension of the newborn. A Multicentre, retrospective study.
AB  - We have compared intravenous magnesium sulphate vs. inhaled nitric oxide in the
      therapy of moderate persistent pulmonary hypertension of the neonate. A
      retrospective collection of clinical data from 58 neonates was carried out in six
      neonatal intensive care units of Southern Italy sharing the same operational
      protocols. In our setting, both drugs were effective in treating moderate
      persistent pulmonary hypertension of the neonate but nitric oxide (NO) treatment
      resulted in much faster amelioration of oxygenation index, taken as a marker of
      the underlying condition. No significant difference was recorded in immediate or
      long-term complications. We conclude that, wherever NO facilities are not readily
      available, magnesium sulphate is a safe and cheaper alternative for first-line
      treatment of moderate persistent pulmonary hypertension of the neonate.

PMID- 18048461
TI  - Pre-exposure purified vero cell rabies vaccine and concomitant routine childhood
      vaccinations: 5-year post-vaccination follow-up study of an infant cohort in
      Vietnam.
AB  - Children have a high risk of exposure to rabies in countries where the disease is
      endemic. This prospective, 5-year study followed two groups of children who had
      received diphtheria, tetanus, whole-cell pertussis and inactivated poliomyelitis
      vaccine (DTP-IPV) at 2, 3, 4 months and 1 year (Group B) or concomitant with
      three doses of purified Vero cell rabies vaccine (PVRV), given at 2, 4 months and
      1 year (Group A). Antibody determinations were made annually for 5 years. Data
      were available from a total of 72 subjects; 30 in Group A and 32 in Group B. In
      Group A, the percentage of patients immunized against rabies (anti-rabies > or =
      0.5 IU/ml) decreased from 100% after the third vaccination to 63%, 5 years later.
      After 5 years, 93.8% in Group A and 96.7% in Group B had seroprotective
      diphtheria antibody titers > or = 0.01 IU/ml, and all subjects had anti-polio
      (type 1, 2 and 3) seroprotective titers > or = 5 1:dil. We conclude that co
      administration of PVRV with DTP-IPV elicited protective antibody concentrations
      to all antigens that persist for at least 5 years, with continued protection
      against rabies in over 60% of subjects. These results are consistent with
      integration of pre-exposure rabies vaccination into the Expanded Program on
      Immunization (EPI) in countries where rabies is endemic.

PMID- 18048462
TI  - Ankle-brachial index and hemostatic markers in the Atherosclerosis Risk in
      Communities (ARIC) study cohort.
AB  - To determine whether elevated levels of hemostatic and inflammatory markers [von
      Willebrand factor (vWF), fibrinogen, D-dimer, factor VII, factor VIII, PAI-1,
      tPA, beta-thromboglobulin (beta-TG), CRP, and WBC count] are associated with
      increased peripheral arterial disease (PAD) prevalence, measured by low ABI, we
      studied 13,778 participants from the ARIC study in a cross-sectional analysis
      after adjustment for major cardiovascular risk factors. PAD was positively
      associated with fibrinogen, vWF, factor VIII, WBC count, D-dimer, beta-TG, and
      CRP (p for trend <0.05) but not with the other markers. Adjusted odds ratios for
      the highest versus the lowest quartile of fibrinogen in men and women,
      respectively, were 3.49 (95% CI 1.68-7.26) and 2.44 (95% CI 1.58-3.77); for vWF
      2.36 (95% CI 1.36-4.07) and 1.45 (95% CI 1.00-2.10); for factor VIII 2.31 (95% CI
      1.36-3.94) and 1.68 (95% CI 1.14-2.48). In a smaller subset, the sex and risk
      factor adjusted odds ratio for the highest versus the lowest quartile of D-dimer
      was 2.70 (95% CI 1.56-4.65), for beta-TG was 1.80 (95% CI 1.12-2.88), and for CRP
      was 1.57 (95% CI 0.84-2.95). Plasma levels of hemostatic and inflammatory markers
      are elevated in PAD, suggesting these processes are involved in the
      pathophysiology of PAD.

PMID- 18048463
TI  - Beneficial effects of 1-year optimal medical treatment with and without
      additional PTA on inflammatory markers of atherosclerosis in patients with PAD.
      Results from the Oslo Balloon Angioplasty versus Conservative Treatment (OBACT)
      study.
AB  - The influence of optimal medical treatment (OMT) with or without additional
      percutaneous transluminal angioplasty (PTA) on vascular inflammation in
      peripheral arterial occlusive disease (PAD) patients was investigated. Patients
      with intermittent claudication (IC) and angiographically verified PAD were
      randomized to OMT (n = 28) or OMT + PTA (n = 28) and followed for 12 months.
      Ankle-brachial index (ABI), treadmill walking distances (WD), visual analogue
      scale (VAS), and blood sampling for the determination of selected soluble
      biomarkers were undertaken at baseline and after 3 and 12 months. After both 3
      and 12 months, ABI, WD and VAS were highly significantly improved in favour of
      OMT + PTA (p < 0.05 for all). Significant improvements were recorded in both
      groups in serum lipids (p < 0.01 for all), except for triglycerides, and in the
      inflammatory markers P-selectin, interleukin-6, interleukin-10, monocyte
      chemoattractant protein-1 and fibrinogen (p < 0.05 for all). There were, however,
      no differences in the changes from baseline between the groups in any variable.
      Intervention with OMT alone or in combination with PTA did not differ with regard
      to the effects on serum lipids and markers of inflammation in our population of
      PAD patients. The combined treatment was, however, better for the treadmill
      walking distance.

PMID- 18048464
TI  - Increased levels of apoptosis in gastrocnemius skeletal muscle in patients with
      peripheral arterial disease.
AB  - Intermittent claudication (IC) is the major clinical manifestation of peripheral
      arterial disease (PAD). Apoptosis has been linked to skeletal muscle
      pathophysiology in other chronic diseases such as congestive heart failure. This
      study tested the hypothesis that there would be increased levels of apoptosis in
      the skeletal muscle of patients with PAD compared with control individuals. In
      total, 26 individuals with PAD and 28 age-appropriate controls underwent studies
      of peak oxygen consumption (peak VO2) and a gastrocnemius muscle biopsy in the
      most symptomatic leg. Muscle biopsies were analyzed for apoptosis and caspase-3
      activity. Patients with PAD had a reduced peak VO2 compared with controls.
      Apoptosis was increased in those with PAD compared with age-appropriate controls
      (3.83% +/- 2.6 vs 1.53% +/- 0.96; p < 0.001). In conclusion, PAD is associated
      with increased levels of apoptosis in the peripheral skeletal muscle. Further
      study is required to ascertain whether apoptosis plays a role in decreased
      functional capacity.

PMID- 18048465
TI  - Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque
      neovascularization: a new surrogate marker of atherosclerosis?
AB  - An atherosclerotic plaque requires a nutrient blood supply, which is
      predominantly derived from arterial vasa vasorum. A variety of factors
      (environmental and genetic) contribute to the initiation and growth of
      atherosclerosis within vessel walls. Chemotactic factors, such as tissue ischemic
      and hypoxic factors, stimulate the release of vascular endothelial growth factor
      (VEGF) proteins, resulting in vessel wall angiogenesis. These developments often
      precede the formation of the luminal plaque. In this report, we describe the use
      of contrast-enhanced carotid ultrasound (CECU) imaging for the detection and
      quantification of intra-plaque neovascularization. The efficacy of CECU was
      measured against the neovascular density observed within the tissue specimens
      obtained at the time of carotid endarterectomy surgery. The objective of this
      study was to provide a histologic correlation between CECU and carotid artery
      atherosclerotic plaque neovascularization. Fifteen patients with significant
      atherosclerotic carotid artery disease received a CECU examination prior to
      undergoing a carotid endarterectomy (CEA). Two patients received bilateral
      endarterectomies, resulting in a total of 17 cases. At the time of surgery,
      carotid plaque samples were surgically removed and stained with specific vascular
      markers (CD31, CD34, von Willebrand factor, and hemosiderin) designed to identify
      the presence and degree of neovascularization. The intra-plaque
      neovascularization recorded on preoperative CECU was correlated with the degree
      of neovascularization noted in the tissue specimens. The CECU neovascularization
      was correlated to CD31-stained tissue specimens. This correlation value was 0.68
      using Spearman's rank method. When CECU results were correlated with the other
      histologic markers (CD34, von Willebrand factor, and hemosiderin), a correlation
      of 0.50 was obtained. In conclusion, contrast-enhanced carotid ultrasound
      correlated to the presence and degree of intra-plaque neovascularization as
      determined from histology specimens.

PMID- 18048466
TI  - An overview of cytokine interactions in atherosclerosis and implications for
      peripheral arterial disease.
AB  - Over the last three decades, a surge in research into the inflammatory
      pathophysiology of atherosclerosis has highlighted an array of cytokines and
      other inflammatory mediators associated with underlying inflammatory burden. The
      ability to identify and simultaneously measure multiple cytokines in peripheral
      blood highlights their potential as biomarkers of atherosclerosis. This has
      prompted much research in vascular medicine to identify the ;at-risk' groups for
      atherostenotic or atheroaneurysmal disease. This review is compiled with similar
      intentions and aims to discern the relevant evidence for cytokine profiling in
      peripheral arterial disease (PAD), where such information is lacking, while
      providing a holistic overview of cytokine interactions in atherosclerosis. This
      is pertinent given that cytokine profiles from coronary artery disease and aortic
      aneurysm studies cannot be directly extrapolated to PAD due to differences in
      inflammatory environments that exist in these conditions. Whilst plaque
      morphology and blood rheology play an important role in the cardiac
      manifestations of atherosclerosis, tissue thrombogenecity is very important in
      PAD. Further, cytokines act in concert rather than in isolation in a disease
      process, and no single cytokine in a cross-sectional model is able to serve as an
      absolute screening marker. Thus, it is essential to understand the regulation of
      cytokine production in atherosclerosis prior to evaluating the viability and
      merits of a multimarker approach for clinical risk stratification in PAD.

PMID- 18048467
TI  - Rosiglitazone improves endothelial function and inflammation but not asymmetric
      dimethylarginine or oxidative stress in patients with type 2 diabetes mellitus.
AB  - We compared the vascular effects of rosiglitazone versus glyburide and evaluated
      asymmetric dimethylarginine (ADMA) and oxidative stress as potential mechanisms
      associated with changes in vascular health in patients with type 2 diabetes
      mellitus (T2DM). Patients were randomized to 6 months of either rosiglitazone (n
      = 20) or glyburide (n = 16) in addition to metformin. The following variables
      were measured pre- and post-treatment: glucose, insulin, homeostasis model
      assessment (HOMA), hemoglobin A1c (HbA1c), C-peptide, blood pressure, lipids, C
      reactive protein (CRP), ADMA, 8-isoprostane, oxidized LDL cholesterol, brachial
      artery flow-mediated dilation (FMD), endothelium-independent dilation (EID), and
      brachial and carotid artery stiffness. Rosiglitazone and glyburide treatment
      resulted in significant and equivalent decreases in glucose (p < 0.0001) and
      HbA1c (p < 0.0001), with a trend toward decreased HOMA (p = 0.09). Rosiglitazone
      significantly decreased C-peptide (p < 0.01) with a strong trend toward decreased
      fasting insulin (p = 0.05). Rosiglitazone reduced CRP compared with glyburide (p
      = 0.001), but no differences were observed between groups for ADMA or the markers
      of oxidative stress. Rosiglitazone significantly improved FMD (p < 0.05) with
      trends toward improvements in carotid artery distension (p = 0.099) and
      distensibility (p = 0.078). In conclusion, compared with glyburide, rosiglitazone
      improves endothelial function and CRP in patients with T2DM. These improvements
      are not associated with reductions in ADMA or markers of oxidative stress.

PMID- 18048468
TI  - Persistent left superior vena cava (PLSVC) with anomalous left hepatic vein
      drainage into the right atrium: role of imaging and clinical relevance.
AB  - Persistent left superior vena cava (PLSVC) is a very rare and yet the most
      commonly described thoracic venous anomaly in medical literature. It has a 10
      fold higher incidence with congenital heart disease. PLSVC often becomes apparent
      when an unknown PLSVC is incidentally discovered during central venous line
      placement, intracardiac electrode/pacemaker placement or cardiopulmonary bypass,
      where it may cause technical difficulties and life-threatening complications.
      PLSVC is also associated with disturbances of cardiac impulse formation and
      conduction including varying degrees of heart blocks, supraventricular
      arrhythmias and Wolff Parkinson White syndrome. We describe the case of an 86
      year-old male with a history of coronary artery disease and chronic atrial
      fibrillation who presented with worsening dyspnea and syncopal episodes. An ECG
      was consistent with complete heart block. During lead placement for the
      pacemaker, a left subclavian approach was unsuccessful. A left venogram was
      performed through the brachial vein that demonstrated a left superior vena cava.
      The diagnosis was confirmed with echocardiography using a bubble study and also a
      chest CT. The anatomy was unique as there was anomalous left hepatic vein
      drainage into the right atrium. The case provides insight into the diagnostic
      modalities and clinical considerations of this unusual thoracic venous anomaly.

PMID- 18048469
TI  - Applying the gender lens to abdominal aortic aneurysm screening.

PMID- 18048470
TI  - Why TASC II?

PMID- 18048471
TI  - Arterial aging: pathophysiological principles.
AB  - In the nineteenth century, prior to the introduction of the cuff
      sphygmomanometer, arteriosclerosis (stiffening of arteries) was recognized by
      clinicians and by life insurance companies as an indicator of vascular aging and
      cardiovascular risk, even in asymptomatic individuals. Through the twentieth
      century, views on aging came to focus on values of systolic and diastolic
      pressure and on obstructive atherosclerotic disease. Such focus deflected
      attention from the primary aging change which occurs in all societies, and is
      represented by stiffening and dilation of the proximal aorta. This review
      emphasizes the cushioning function of elastic arteries - principally the aorta -
      and how in youth this results in optimal interaction with the heart, and optimal
      steady flow through peripheral resistance vessels. Aortic stiffening with age is
      principally due to fatigue and fracture of elastin lamellae, with transfer of
      stress to stiffer collagenous components. Stiffening increases left ventricular
      load and myocardial blood requirement, but limits the capacity for blood supply
      during diastole. Consequences are cardiac failure and predisposition to
      ischaemia. The second, under-appreciated effect of aortic stiffening is
      transmission of flow pulsations downstream into vasodilated organs, principally
      brain and kidney, where pulsatile energy is dissipated and fragile microvessels
      are damaged. This accounts for micro infarcts and microhaemorrhages, with
      specialized cell damage, cognitive decline and renal failure. The aging process
      can be best monitored by change in the arterial pressure wave rather than by
      reliance on the cuff sphygmomanometer. This reintroduces the approaches by
      clinicians and life insurance examiners of the nineteenth century, endorses
      modern treatments for established disease, and holds the promise of detecting
      premature arterial degeneration, and better applying lifestyle measures and
      vasoactive medications to modify the aging process.

PMID- 18048472
TI  - Risk assessment in the patient with established peripheral arterial disease.
AB  - Office-based cardiovascular risk prediction continues to challenge practitioners
      in primary and secondary risk stratification settings. In patients with
      established peripheral arterial disease (PAD), the risk of cardiovascular events
      (i.e. death or morbidity due to coronary heart disease and/or cerebrovascular
      disease) is high, yet traditional risk factors and the ankle-brachial index (ABI)
      do not provide a complete secondary risk prediction. In this population, office
      based cardiovascular risk stratification may be improved by surrogate markers of
      the systemic atherosclerotic burden, as well as markers of systemic inflammation.
      This review will evaluate the utility of the ABI, clinical stage of disease, and
      the emerging role of C-reactive protein (CRP) and other inflammatory markers in
      secondary risk prediction in PAD. Defining which patients are in the highest
      category of risk may direct health care providers to emphasize secondary
      preventive measures, and facilitate patient adherence to recommended medical
      therapies and smoking cessation.

PMID- 18048473
TI  - The role of exercise training in peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is currently a major health problem affecting 8
      12 million Americans, 15-40% of whom will have intermittent claudication that can
      lead to substantial impairment in their ability to carry out normal daily
      activities as well as perform the recommended cardiovascular exercise. Supervised
      exercise training is an effective tool in the treatment of claudication and is
      currently a recommended first-line therapy for patients with this condition. In
      addition to improving pain-free walking distance and quality of life, supervised
      exercise training can improve many cardiovascular risk factors, possibly reducing
      the risk for subsequent myocardial infarction, stroke, and death. This paper will
      review the benefits of supervised exercise training in patients with PAD.

PMID- 18048475
TI  - Images in vascular medicine. Giant cell arteritis presenting with acute
      myocardial infarction.

PMID- 18048474
TI  - ACCF/AHA 2007 Clinical Competence Statement on vascular imaging with computed
      tomography and magnetic resonance.

PMID- 18048476
TI  - Images in vascular medicine. Rapid expansion of an inflammatory abdominal aortic
      aneurysm.

PMID- 18048477
TI  - Prediction-based protein engineering of domain I of Cry2A entomocidal toxin of
      Bacillus thuringiensis for the enhancement of toxicity against lepidopteran
      insects.
AB  - Issues relating to sustenance of the usefulness of genetically modified first
      generation Bt crop plants in the farmer's field are of great concern for crop
      scientists. Additional biotechnological strategies need to be in place to
      safeguard the possibility for yield loss of Bt crop by other lepidopteran insects
      that are insensitive to the Cry1A toxin, and also against the possibility for
      emergence of resistant insects. In this respect, Cry2A toxin has figured as a
      prospective candidate to be the second toxin to offer the required protection
      along with Cry1A. In the present study, the entomocidal potency of Cry2A toxin
      was enhanced through knowledge-based protein engineering of the toxin molecule.
      Deletion of 42 amino acid residues from the N-terminal end of the peptide
      followed by the replacement of Lys residues by nonpolar amino acids in the
      putative transmembrane region including the introduction of Pro resulted in a 4.1
      6.6-fold increase in the toxicity of the peptide against three major lepidopteran
      insect pests of crop plants.

PMID- 18048478
TI  - 5-Lipoxygenase-derived lipid mediators are not required for the development of
      NSAID-induced inflammatory bowel disease in IL-10-/- mice.
AB  - Leukotrienes are potent lipid mediators derived from the metabolism of
      arachidonic acid by the enzyme 5-lipoxygenase (5-LO). Elevated levels of the
      proinflammatory leukotriene LTB(4) have been found in preclinical models of
      inflammatory bowel disease (IBD) as well as in colon tissue from individuals with
      IBD. We therefore determined the extent to which absence of 5-LO-derived lipid
      mediators would alter the colitis in IL-10(-/-) mice, a model of human IBD. IL
      10(-/-)/5-LO(-/-) mice were generated and were healthy. Absence of 5-LO did not
      alter the development of spontaneous colitis in IL-10-deficient mice. We then
      evaluated the extent to which absence of 5-LO would alter the development of
      NSAID-induced colitis in IL-10(-/-) mice. Absence of 5-LO did not delay the onset
      or alter the severity of inflammation in NSAID-treated IL-10(-/-) mice. At an
      early time point, 3 days after NSAID treatment was initiated, a qualitative
      increase in the number of dendritic cells and CD4(+) T cells was noted in the
      colons of IL-10(-/-)/5-LO(-/-); however, this difference was no longer present
      after 14 days of NSAID treatment. Absence of 5-LO did not alter the degree of
      neutrophil infiltration into the in this model. Absence of 5-LO does not alter
      the development of IFN-gamma producing Th1-type CD4(+) T cells or IL-17 producing
      CD4(+) T cells. Absence of 5-LO-derived mediators did not alter the expression of
      the adhesion molecules ICAM-1 and P-selectin. Development of colitis in IL-10(-/
      ) mice was associated with increased levels of the 5-LO-derived anti-inflammatory
      lipoxin LXA(4). These studies demonstrate that 5-LO-derived leukotrienes are not
      required for the development or maintenance of spontaneous or NSAID-induced
      colonic inflammation in IL-10(-/-) mice.

PMID- 18048479
TI  - Simultaneous deletion of ghrelin and its receptor increases motor activity and
      energy expenditure.
AB  - Administration of chemically synthesized ghrelin (Ghr) peptide has been shown to
      increase food intake and body adiposity in most species. However, the biological
      role of endogenous Ghr in the molecular control of energy metabolism is far less
      understood. Mice deficient for either Ghr or its receptor (the growth hormone
      secretagogue receptor, GHS-R1a) seem to exhibit enhanced protection against high
      fat diet-induced obesity but do not show a substantial metabolic phenotype on a
      standard diet. Here we present the first mouse mutant lacking both Ghr and the
      Ghr receptor. We demonstrate that simultaneous genetic disruption of both genes
      of the Ghr system leads to an enhanced energy metabolism phenotype. Ghr/Ghr
      receptor double knockout (dKO) mice exhibit decreased body weight, increased
      energy expenditure, and increased motor activity on a standard diet without
      exposure to a high caloric environment. Mice on the same genetic background
      lacking either the Ghr or the Ghr receptor gene did not exhibit such a phenotype
      on standard chow, thereby confirming earlier reports. No differences in food
      intake, meal pattern, or lean mass were observed between dKO, Ghr-deficient, Ghr
      receptor-deficient, and wild-type (WT) control mice. Only dKO showed a slight
      decrease in body length. In summary, simultaneous deletion of Ghr and its
      receptor enhances the metabolic phenotype of single gene-deficient mice compared
      with WT mice, possibly suggesting the existence of additional, as of yet unknown,
      molecular components of the endogenous Ghr system.

PMID- 18048480
TI  - Role of mitochondria in spontaneous rhythmic activity and intracellular calcium
      waves in the guinea pig gallbladder smooth muscle.
AB  - Mitochondrial Ca(2+) handling has been implicated in spontaneous rhythmic
      activity in smooth muscle and interstitial cells of Cajal. In this investigation
      we evaluated the effect of mitochondrial inhibitors on spontaneous action
      potentials (APs), Ca(2+) flashes, and Ca(2+) waves in gallbladder smooth muscle
      (GBSM). Disruption of the mitochondrial membrane potential with carbonyl cyanide
      3-chlorophenylhydrazone, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone,
      rotenone, and antimycin A significantly reduced or eliminated APs, Ca(2+)
      flashes, and Ca(2+) waves in GBSM. Blockade of ATP production with oligomycin did
      not alter APs or Ca(2+) flashes but significantly reduced Ca(2+) wave frequency.
      Inhibition of mitochondrial Ca(2+) uptake and Ca(2+) release with Ru360 and CGP
      37157, respectively, reduced the frequency of Ca(2+) flashes and Ca(2+) waves in
      GBSM. Similar to oligomycin, cyclosporin A did not alter AP and Ca(2+) flash
      frequency but significantly reduced Ca(2+) wave activity. These data suggest that
      mitochondrial Ca(2+) handling is necessary for the generation of spontaneous
      electrical activity and may therefore play an important role in gallbladder tone
      and motility.

PMID- 18048481
TI  - Mortality and preoperative cardiac function in vascular amputees: an N-terminal
      pro-brain natriuretic peptide (NT-proBNP) pilot study.
AB  - OBJECTIVE: To determine preoperative ventricular function in vascular amputees by
      measuring N-terminal pro-brain natriuretic peptide (NT-proBNP) and to analyse the
      relationship between NT-proBNP levels and 30-day postoperative mortality. DESIGN:
      Prospective pilot study. SUBJECTS AND METHODS: In 19 patients planned for a lower
      limb amputation for non-reconstructable peripheral arterial disease NT-proBNP was
      measured the day before amputation. RESULTS: Four amputees died within 30 days
      after the amputation. In 17 of 19 patients NT-proBNP values were found more than
      2 standard deviations above the age corrected reference value. Pre-amputation NT
      proBNP levels did not differ significantly between non-survivors and survivors (P
      = 0.162). CONCLUSION: Preoperative NT-proBNP levels are not significantly related
      to 30-day mortality after lower limb amputation procedure. Preoperative NT-proBNP
      levels are very high, indicating that serious ventricular dysfunction may be
      present in vascular amputees.

PMID- 18048482
TI  - The impact of introducing an ICF-based rehabilitation tool on staff satisfaction
      with multidisciplinary team care in rheumatology: an exploratory study.
AB  - OBJECTIVE: To investigate the impact of introducing a rehabilitation tool on
      multidisciplinary team members' satisfaction with team functioning, team
      conferences and written information exchange. DESIGN: Pretest posttest design.
      SETTING: Day patient and inpatient wards of a rheumatology rehabilitation clinic.
      SUBJECTS: Members of two multidisciplinary teams. INTERVENTIONS: The introduction
      of an electronic version of the Rehabilitation Activities Profile. MAIN MEASURES:
      The Group Environment Scale and questionnaires on satisfaction with team
      conferences and administrative procedures administered before (T1) and 12 months
      after (T2) the introduction of the Rehabilitation Activities Profile. RESULTS:
      The Group Environment Scale cohesion subscale was significantly higher at T2 than
      at T1 in the day patient setting (mean difference 1.9; 95% confidence interval
      (CI) 0.3; 3.4), whereas in the inpatient setting the Group Environment Scale
      cohesion and the order and organization subscales were significantly lower (mean
      differences -3.0; 95% CI -4.7; -1.3 and -2.7; 95% CI -4.3; -1.1, respectively).
      Satisfaction with team conferences was significantly higher at T2 compared with
      T1 in the day patient setting (mean difference total score 0.6; 95% CI 0.3; 1.0),
      but not in the inpatient setting (mean difference -0.3; 95% CI -0.7; 0.2). In
      both settings, the proportions of health professionals spending >10 minutes on
      administrative tasks per patient contact were significantly higher at T2 than at
      T1. CONCLUSIONS: In the day patient setting, the introduction of a rehabilitation
      tool had a positive effect on team members' satisfaction with team functioning
      and team conferences, whereas in the inpatient setting the effect was absent or
      the opposite. In both settings, the time spent on administrative tasks increased.

PMID- 18048483
TI  - Physical limitations and self-rated overall health in family medicine patients.
AB  - OBJECTIVE: To assess how physical limitations relate to self-rated health among
      family medicine patients after adjustment for severity of illness. DESIGN: A
      telephone survey of family medicine patients, linked with medical record
      information. SETTING: A large family medicine department in Rochester, Minnesota,
      USA. SUBJECTS: Self-ratings of health were linked to medical records for 804
      adult patients. RESULTS: Adjusting for severity and other confounders using
      multiple logistic regression analysis revealed that having physical limitations
      was inversely and independently related to good self-rated health (adjusted odds
      ratio = 0.20, P<0.001). Odds ratios also were lower for high severity of illness
      (adjusted odds = 0.43). Morbidly obese patients and patients older than 65 years
      of age also had reduced odds of good self-rated health. CONCLUSIONS: In our
      sample of family medicine patients, part of the disparity in health status
      experienced by people with physical limitations is attributable to greater
      severity of illness, age and obesity.

PMID- 18048484
TI  - Screening for depression after stroke: an exploration of professionals'
      compliance with guidelines.
AB  - OBJECTIVE: National guidelines recommend screening for poststroke depression, but
      compliance is low. This research studied staff compliance in stroke units using
      the theory of planned behaviour to investigate influences upon screening. DESIGN:
      The study used a questionnaire based on a semi-structured interview and measuring
      the theory of planned behaviour components. SETTING: Sixteen stroke units
      throughout the UK were included. SUBJECTS: Seventy-five health care professionals
      in stroke services participated. MAIN MEASURES: A postal questionnaire with 7
      point rating scales and open-ended questions was used. RESULTS: Response rates
      were low, but the 75 returns demonstrated poor compliance for screening, despite
      positive attitudes towards it. Five variables, including three of the theory of
      planned behaviour components, predicted intention to screen: perceived control
      over screening, perceived expectations of others (direct and indirect normative
      beliefs), awareness of guidelines and screening being part of routine assessment.
      Perceived expectations of others, perceived control and awareness of guidelines
      also differentiated those intending to screen from 'non-intenders'. Being
      knowledgeable about screening, having screening in the job role and belief in its
      clinical value were additional facilitating factors, while time pressure and
      concerns about screening tests were barriers. Profession and psychology input
      were not associated with screening. CONCLUSIONS: The theory of planned behaviour
      provides a framework for understanding screening intentions. Both individual and
      organizational factors were associated with screening. Compliance may be enhanced
      by: training to increase knowledge and skills, providing evidence of the utility,
      increasing awareness of guidelines, support from colleagues and integrating mood
      assessment into job roles and routine assessment.

PMID- 18048485
TI  - CYP2C19 inhibition: the impact of substrate probe selection on in vitro
      inhibition profiles.
AB  - Understanding the potential for cytochrome P450 (P450)-mediated drug-drug
      interactions is a critical part of the drug discovery process. Factors such as
      nonspecific binding, atypical kinetics, poor effector solubility, and varying
      ratios of accessory proteins may alter the kinetic behavior of an enzyme and
      subsequently confound the extrapolation of in vitro data to the human situation.
      The architecture of the P450 active site and the presence of multiple binding
      regions within the active site may also confound in vitro-in vivo extrapolation,
      as inhibition profiles may be dependent on a specific inhibitor-substrate
      interaction. In these studies, the inhibition profiles of a set of 24 inhibitors
      were paneled against the CYP2C19 substrate probes (S)-mephenytoin, (R)
      omeprazole, (S)-omeprazole, and (S)-fluoxetine, on the basis of their inclusion
      in recent U.S. Food and Drug Administration guidance for in vitro drug-drug
      interactions with CYP2C19. (S)-Mephenytoin was inhibited an average of 5.6-fold
      more potently than (R)- or (S)-omeprazole and 9.2-fold more potently than (S)
      fluoxetine. Hierarchical clustering of the inhibition data suggested three
      substrate probe groupings, with (S)-mephenytoin exhibiting the largest difference
      from the rest of the substrate probes, (S)-fluoxetine exhibiting less difference
      from (S)-mephenytoin and the omeprazoles and (R)- and (S)-omeprazole exhibiting
      minimal differences from each other. Predictions of in vivo inhibition potency
      based on the in vitro data suggest that most drug-drug interactions will be
      identified by either (S)-mephenytoin or omeprazole, although the expected
      magnitude of the interaction may vary depending on the chosen substrate probe.

PMID- 18048486
TI  - Metabolism of the trisubstituted purine cyclin-dependent kinase inhibitor
      seliciclib (R-roscovitine) in vitro and in vivo.
AB  - Seliciclib (R-roscovitine, CYC202) is a small molecule inhibitor of cyclin
      dependent kinases currently in phase II clinical trials as an anticancer agent.
      We examined the metabolism of seliciclib in vitro and in vivo. Using radiolabeled
      seliciclib we found that cytochrome P450 (P450)-mediated metabolism in liver
      microsomes from human, rat, mouse, rabbit, monkey, and dog was rapid to a number
      of metabolic species, one of the most prevalent being a carboxylate previously
      identified in urine from rats and mice dosed with seliciclib. Metabolism was
      fastest in mouse microsomes and slowest in microsomes from dog. Using
      characterized human microsomes, we identified the P450s responsible for this
      metabolism as CYP3A4 and CYP2B6. Glucuronidation of seliciclib and its
      metabolites was shown to be a major elimination process in bile duct-cannulated
      rats dosed with [(14)C]seliciclib at 10 mg/kg. Elimination by the fecal route
      accounted for up to 65% of the administered dose, whereas urinary excretion
      accounted for up to 43%. Almost half of the administered dose was found to be
      eliminated via the bile, and elimination was found to be rapid, with up to 88% of
      the dose being excreted within the first 24 h. Preliminary experiments indicated
      that UDP-glucuronosyltransferase (UGT) 1A3, 1A9, and 2B7 were involved in the
      conjugation of seliciclib. Seliciclib was further shown in vitro to inhibit the
      activity of some of the enzymes responsible for its metabolism. Cytochrome P450s
      CYP3A4 and CYP2C9 and UGT1A1 were all inhibited at concentrations achieved in
      human trials, which raises the possibility of drug-drug interactions in the
      clinic.

PMID- 18048488
TI  - Hepatobiliary excretion of silibinin in normal and liver cirrhotic rats.
AB  - Silibinin is the main biologically active flavonolignan extracted from the seeds
      and fruits of milk thistle and has potential efficacy in the treatment of liver
      disease. The aim of the present study was to examine the hepatobiliary excretion
      of silibinin and its effect on dimethylnitrosamine (DMN)-induced liver cirrhosis.
      The experiments were divided into five groups: 10, 30, and 50 mg/kg silibinin
      alone, 30 mg/kg silibinin coadministered with cyclosporin A (CsA), and 50 mg/kg
      silibinin with liver cirrhosis induced by DMN. The data indicated that silibinin
      had dose-related pharmacokinetics in the dose ranges of 10 to 50 mg/kg. All of
      the unconjugated or total (unconjugated + conjugated) silibinin concentrations in
      the bile were significantly higher than those in plasma at the sampling time
      points at each dose, suggesting active hepatobiliary excretion. When
      coadministered with CsA, the area under the concentration versus time curve (AUC)
      in bile was significantly decreased. This result suggested that the active
      silibinin efflux might be partially inhibited by P-glycoprotein. In the DMN
      induced liver cirrhotic rats, the AUC of plasma unconjugated silibinin was
      reduced by 53%; however, total silibinin was increased by 182%. These results
      together suggest that the phase II conjugative reaction of silibinin was blocked
      by treatment with DNM.

PMID- 18048487
TI  - Physical incorporation of NADPH-cytochrome P450 reductase and cytochrome P450
      into phospholipid vesicles using glycocholate and Bio-Beads.
AB  - In a previous study from our laboratory (Drug Metab Dispos 34: 660-666, 2006), we
      found several limitations with published methods (cholate gel filtration and
      cholate dialysis) for the incorporation of cytochromes P450 and P450 reductase
      into phospholipid vesicles. We found that a significant proportion of reductase
      was not incorporated in the vesicles when the amount of reductase was equal to or
      greater than that of CYP2B4 in the systems reconstituted with
      phosphatidylcholine. Furthermore, implementation of these methods compromised the
      ability of the CYP2B4 to form a ferrous carbon monoxy complex. In the current
      study, a comparison of results using the detergent-dialysis method with five
      similar detergents having the "bile salt" ring structure showed that glycocholate
      results in the greatest incorporation of reductase and the least loss in the
      ferrous carbon monoxy CYP2B4 complex. The method is further improved by using Bio
      Beads SM-2 to remove detergent instead of the lengthy dialysis procedure or size
      exclusion chromatography that significantly dilutes the protein and lipid
      concentrations of the preparation. The method is shown to be applicable over a
      range of lipid/CYP2B4 ratios, and by using assay methods for total lipid,
      reductase, and CYP2B4, this improved reconstitution method resulted in increased
      incorporation efficiencies while minimizing the protein degradation inherent with
      these procedures.

PMID- 18048489
TI  - The first aspartic acid of the DQxD motif for human UDP-glucuronosyltransferase
      1A10 interacts with UDP-glucuronic acid during catalysis.
AB  - All UDP-glucuronosyltransferase enzymes (UGTs) share a common cofactor, UDP
      glucuronic acid (UDP-GlcUA). The binding site for UDP-GlcUA is localized to the C
      terminal domain of UGTs on the basis of amino acid sequence homology analysis and
      crystal structures of glycosyltransferases, including the C-terminal domain of
      human UGT2B7. We hypothesized that the (393)DQMDNAK(399) region of human UGT1A10
      interacts with the glucuronic acid moiety of UDP-GlcUA. Using site-directed
      mutagenesis and enzymatic analysis, we demonstrated that the D393A mutation
      abolished the glucuronidation activity of UGT1A10 toward all substrates. The
      effects of the alanine mutation at Q(394),D(396), and K(399) on glucuronidation
      activities were substrate-dependent. Previously, we examined the importance of
      these residues in UGT2B7. Although D(393) (D(398) in UGT2B7) is similarly
      critical for UDP-GlcUA binding in both enzymes, the effects of Q(394) (Q(399) in
      UGT2B7) to Ala mutation on activity were significant but different between
      UGT1A10 and UGT2B7. A model of the UDP-GlcUA binding site suggests that the
      contribution of other residues to cosubstrate binding may explain these
      differences between UGT1A10 and UGT2B7. We thus postulate that D(393) is critical
      for the binding of glucuronic acid and that proximal residues, e.g., Q(394)
      (Q(399) in UGT2B7), play a subtle role in cosubstrate binding in UGT1A10 and
      UGT2B7. Hence, this study provides important new information needed for the
      identification and understanding of the binding sites of UGTs, a major step
      forward in elucidating their molecular mechanism.

PMID- 18048490
TI  - Cytochrome P450 expression and regulation in CYP3A4/CYP2D6 double transgenic
      humanized mice.
AB  - Analysis of the developmental and sexual expression of cytochrome P450 drug
      metabolizing enzymes is impeded by multiple and varied external factors that
      influence its regulation. In the present study, a CYP2D6/CYP3A4-double transgenic
      (Tg-CYP2D6/CYP3A4) mouse model was employed to investigate hepatic CYP2D6 and
      CYP3A4 ontogeny and sexual dimorphism. Both age and sex have considerable effects
      on hepatic CYP3A4 protein expression in 3- to 8-week-old transgenic mice, whereas
      neither factor alters CYP2D6 content. Constitutive CYP2D6 expression resulted in
      2- to 3-fold higher dextromethorphan O-demethylase activity in Tg-CYP2D6/CYP3A4
      mouse liver microsomes compared with wild-type mice. In contrast, expression of
      CYP3A4 in transgenic mouse livers did not increase dextromethorphan N-demethylase
      and midazolam 1'-hydroxylase activities. Pretreatment with pregnenolone 16alpha
      carbonitrile (PCN) and 1,4-bis-2-(3, 5-dichloropyridyloxy)-benzene (TCPOBOP)
      elevated CYP3A4 expression in double transgenic mice. Interestingly, induction of
      hepatic CYP3A4 was greater in females than age- and treatment-matched males.
      Consequently, the increase in midazolam 1'-hydroxylase activity was markedly
      higher in 8-week-old female mice than in corresponding males (8-fold versus 6
      fold for PCN treatment and 6-fold versus 5-fold for TCPOBOP). Furthermore,
      increases in testosterone 6beta-hydroxylase activity after CYP3A induction were
      relatively lower compared with those in midazolam 1'-hydroxylation for age-, sex
      , and treatment-matched mice. The difference in CYP3A4 expression and induction
      between male and female mice suggests that women may be more susceptible to
      CYP3A4-mediated drug-drug interactions, and the extent of drug-drug interactions
      could be substrate dependent.

PMID- 18048491
TI  - Osteopontin expression in human and murine obesity: extensive local up-regulation
      in adipose tissue but minimal systemic alterations.
AB  - Obesity is associated with a chronic low-grade inflammation characterized by
      macrophage infiltration of adipose tissue (AT) that may underlie the development
      of insulin resistance and type 2 diabetes. Osteopontin (OPN) is a multifunctional
      protein involved in various inflammatory processes, cell migration, and tissue
      remodeling. Because these processes occur in the AT of obese patients, we studied
      in detail the regulation of OPN expression in human and murine obesity. The study
      included 20 morbidly obese patients and 20 age- and sex-matched control subjects,
      as well as two models (diet-induced and genetic) of murine obesity. In high-fat
      diet-induced and genetically obese mice, OPN expression was drastically up
      regulated in AT (40 and 80-fold, respectively) but remained largely unaltered in
      liver (<2-fold). Moreover, OPN plasma concentrations remained unchanged in both
      murine models of obesity, suggesting a particular local but not systemic
      importance for OPN. OPN expression was strongly elevated also in the AT of obese
      patients compared with lean subjects in both omental and sc AT. In addition, we
      detected three OPN isoforms to be expressed in human AT and, strikingly, an
      obesity induced alteration of the OPN isoform expression pattern. Analysis of AT
      cellular fractions revealed that OPN is exceptionally highly expressed in AT
      macrophages in humans and mice. Moreover, OPN expression in AT macrophages was
      strongly up-regulated by obesity. In conclusion, our data point toward a specific
      local role of OPN in obese AT. Therefore, OPN could be a critical regulator in
      obesity induced AT inflammation and insulin resistance.

PMID- 18048492
TI  - Hypothalamic phosphatidylinositol 3-kinase pathway of leptin signaling is
      impaired during the development of diet-induced obesity in FVB/N mice.
AB  - Phosphatidylinositol 3-kinase (PI3K) pathway of leptin signaling plays an
      important role in transducing leptin action in the hypothalamus. Obesity is
      usually associated with resistance to the effect of leptin on food intake and
      energy homeostasis. Although central leptin resistance is thought to be involved
      in the development of diet-induced obesity (DIO), the mechanism behind this
      phenomenon is not clearly understood. To determine whether DIO impairs the effect
      of leptin on hypothalamic PI3K signaling, we fed 4-wk-old FVB/N mice a high-fat
      diet (HFD) or low-fat diet (LFD) for 19 wk. HFD-fed mice developed DIO in
      association with hyperleptinemia, hyperinsulinemia, and impaired glucose and
      insulin tolerance. Leptin (ip) significantly increased hypothalamic PI3K activity
      and phosphorylated signal transducer and activator of transcription 3 (p-STAT3)
      levels in LFD-fed mice but not in DIO mice. Immunocytochemical study confirmed
      impaired p-STAT3 activation in various hypothalamic areas, including the arcuate
      nucleus. We next tested whether both PI3K and STAT3 pathways of leptin signaling
      were impaired during the early period of DIO. Leptin failed to increase PI3K
      activity in DIO mice that were on a HFD for 4 wk. However, leptin-induced p-STAT3
      activation in the hypothalamus measured by Western blotting and
      immunocytochemistry remained comparable between LFD- and HFD-fed mice. These
      results suggest that the PI3K pathway but not the STAT3 pathway of leptin
      signaling is impaired during the development of DIO in FVB/N mice. Thus, a
      defective PI3K pathway of leptin signaling in the hypothalamus may be one of the
      mechanisms of central leptin resistance and DIO.

PMID- 18048493
TI  - Effects of twinning and periconceptional undernutrition on late-gestation
      hypothalamic-pituitary-adrenal axis function in ovine pregnancy.
AB  - The relationships between reduced size at birth, increased activity of the
      hypothalamic-pituitary-adrenal (HPA) axis, and increased risk of disease in
      adulthood are well described in singletons but are much less clear in twins. This
      may be because the physiological processes underlying reduced size at birth are
      different in singletons and twins. Periconceptional undernutrition can cause
      altered activity of the fetal and postnatal HPA axis without altering size at
      birth. However, the independent effects of periconceptional undernutrition and
      twinning on activity of the maternal and fetal HPA axes are not well described.
      We therefore studied maternal and fetal HPA axis function during late gestation
      in twin and singleton sheep pregnancies, either undernourished around conception
      or fed ad libitum. We found that twinning led to suppressed baseline HPA axis
      function and decreased adrenal sensitivity to ACTH stimulation but increased
      fetal pituitary ACTH response both to direct stimulation by CRH (ACTH area under
      the curve response: 29.7 +/- 2.2 vs. 17.1 +/- 1.6 ng/min x ml, P < 0.01) and to
      decreased cortisol negative feedback. In contrast, periconceptional
      undernutrition resulted in a decreased pituitary response (ACTH area under the
      curve response: 19.4 +/- 1.6 vs. 26.1 +/- 2.2 ng/min x ml, P = 0.02) but no
      difference in adrenal response. Thus, the HPA axis function of twin sheep fetuses
      in late gestation is very different from that of control and undernourished
      singletons. If the HPA axis is an important mediator between fetal adaptations
      and adult disease, these data may help explain why the relationship between fetal
      growth and postnatal physiology and disease risk is inconsistent in twins.

PMID- 18048494
TI  - The long pentraxin PTX3 in human endometrium: regulation by steroids and
      trophoblast products.
AB  - Human implantation is characterized by blastocyst attachment to endometrial
      epithelial cells followed by invasion of trophoblast into the maternal decidua.
      There has been an increasing amount of data linking higher levels of the
      pentraxin PTX3, a long pentraxin, to embryo implantation. PTX3 levels were found
      to be higher in patients with preeclampsia and intrauterine growth restriction,
      both conditions caused by faulty implantation. Furthermore, PTX3 knockout mice
      have reduced fertility due to cumulus oopherus malformation as well as
      implantation failure. In a human implantation model, we and others have shown
      that trophoblast action on endometrial stromal cells induces PTX3 expression. In
      this study, we analyzed PTX3 expression throughout the menstrual cycle as well as
      its regulation by hormones involved in the implantation process. We also compared
      PTX3 expression in stromal cells induced by trophoblast conditioned medium to its
      induction by trophoblast coculture. PTX3 mRNA expression in human endometrial
      stromal cells is regulated by progesterone, estrogen, and IL-1 but not human
      chorionic gonadotropin and is increased by both trophoblast-conditioned medium as
      well as trophoblast explants. PTX3 protein production and regulation by these
      factors is shown by Western blot. Based on these findings, we conclude that
      estradiol and progesterone are involved in PTX3 induction and regulation during
      implantation. Also, of the factors secreted by trophoblast, IL-1beta induces PTX3
      in human endometrial stromal cells.

PMID- 18048495
TI  - Nesfatin-1 neurons in paraventricular and supraoptic nuclei of the rat
      hypothalamus coexpress oxytocin and vasopressin and are activated by refeeding.
AB  - Nesfatin-1, a newly discovered satiety molecule, is located in the hypothalamic
      nuclei, including the paraventricular nucleus (PVN) and supraoptic nucleus (SON).
      In this study, fine localization and regulation of nesfatin-1 neurons in the PVN
      and SON were investigated by immunohistochemistry of neuropeptides and c-Fos. In
      the PVN, 24% of nesfatin-1 neurons overlapped with oxytocin, 18% with
      vasopressin, 13% with CRH, and 12% with TRH neurons. In the SON, 35% of nesfatin
      1 neurons overlapped with oxytocin and 28% with vasopressin. After a 48-h fast,
      refeeding for 2 h dramatically increased the number of nesfatin-1 neurons
      expressing c-Fos immunoreactivity by approximately 10 times in the PVN and 30
      times in the SON, compared with the fasting controls. In the SON, refeeding also
      significantly increased the number of nesfatin-1-immunoreactive neurons and NUCB2
      mRNA expression, compared with fasting. These results indicate that nesfatin-1
      neurons in the PVN and SON highly overlap with oxytocin and vasopressin neurons
      and that they are activated markedly by refeeding. Feeding-activated nesfatin-1
      neurons in the PVN and SON could play a role in the postprandial regulation of
      feeding behavior and energy homeostasis.

PMID- 18048496
TI  - Triclocarban enhances testosterone action: a new type of endocrine disruptor?
AB  - Many xenobiotics have been associated with endocrine effects in a wide range of
      biological systems. These associations are usually between small nonsteroid
      molecules and steroid receptor signaling systems. In this report, triclocarban
      (TCC; 3,4,4'-trichlorocarbanilide), a common ingredient in personal care products
      that is used as an antimicrobial agent was evaluated and found to represent a new
      category of endocrine-disrupting substance. A cell-based androgen receptor
      mediated bioassay was used to demonstrate that TCC and other urea compounds with
      a similar structure, which have little or no endocrine activity when tested
      alone, act to enhance testosterone (T)-induced androgen receptor-mediated
      transcriptional activity in vitro. This amplification effect of TCC was also
      apparent in vivo when 0.25% TCC was added to the diet of castrated male rats that
      were supported by exogenous testosterone treatment for 10 d. All male sex
      accessory organs increased significantly in size after the T+TCC treatment,
      compared with T or TCC treatments alone. The data presented here suggest that the
      bioactivity of endogenous hormones may be amplified by exposure to commercial
      personal care products containing sufficient levels of TCC.

PMID- 18048497
TI  - Bisphenol A prevents the synaptogenic response to testosterone in the brain of
      adult male rats.
AB  - Exposure measurement data from several developed countries indicate that human
      beings are widely exposed to low levels of the synthetic xenoestrogen, bisphenol
      A. We reported previously that bisphenol A, even at doses below the reference
      safe daily limit for human exposure, recommended by the U.S. Environmental
      Protection Agency, impairs the synaptogenic response to 17beta-estradiol in the
      hippocampus of ovariectomized rats. Recent experiments revealed that bisphenol A
      also interferes with androgen receptor-mediated transcriptional activities. Thus,
      to investigate whether bisphenol A impairs synaptogenesis in the medial
      prefrontal cortex (mPFC) and hippocampus of adult male rats, castrated and sham
      operated animals were treated with different combinations of bisphenol A (300
      microg/kg), testosterone propionate (1.5 mg/kg), and sesame oil vehicle. The
      brains were processed for electron microscopic stereology, and the number of
      asymmetric spine synapses in the mPFC and CA1 hippocampal area was estimated. In
      both regions analyzed, bisphenol A reduced the number of spine synapses in sham
      operated, gonadally intact animals, which was accompanied by a compensatory
      increase in astroglia process density. In addition, bisphenol A prevented both
      the prefrontal and hippocampal synaptogenic response to testosterone
      supplementation in castrated males. These results demonstrate that bisphenol A
      interferes with the synaptogenic response to testosterone in the mPFC and
      hippocampus of adult male rats. Because the hippocampal synaptogenic action of
      androgens seems to be independent of androgen and estrogen receptors in males,
      the potential mechanisms that underlie these negative effects of bisphenol A
      remain the subject of further investigation.

PMID- 18048498
TI  - Physiological concentration of 17beta-estradiol on sympathetic reinnervation in
      ovariectomized infarcted rats.
AB  - 17beta-Estradiol (E2) has been shown to exert antiarrhythmic effect after
      myocardial infarction; however, the mechanisms remain unclear. This study was
      performed to determine whether E2 exerts beneficial effects through attenuated
      sympathetic hyperreinnervation after infarction. Two weeks after ovariectomy,
      female Wistar rats were assigned to coronary artery ligation or sham operation.
      Twenty-four hours after coronary ligation, rats underwent one of five treatments:
      1) sc vehicle treatment (control), 2) sc E2 treatment, 3) sc E2 treatment +
      tamoxifen (a potent estrogen receptor antagonist), 4) bosentan (an endothelin
      receptor blocker), or 5) sc E2 treatment + bosentan and followed for 4 wk.
      Myocardial endothelin-1 and norepinephrine levels at the remote zone revealed a
      significant elevation in control infarcted rats, compared with sham-operated
      rats, which is consistent with sympathetic hyperinnervation after infarction.
      Sympathetic hyperinnervation was blunted after giving the rats either E2 or
      bosentan, assessed by immunohistochemical analysis of tyrosine hydroxylase,
      growth-associated protein 43 and neurofilament, and Western blotting and real
      time quantitative RT-PCR of nerve growth factor. Arrhythmic scores during
      programmed stimulation in E2-treated infarcted rats were significantly lower than
      in control-infarcted rats. Addition of bosentan did not have additional
      beneficial effects, compared with rats treated with E2 alone. The beneficial
      effect of E2 on sympathetic hyperinnervation was abolished by tamoxifen. Our data
      indicated that E2 has a role for sympathetic hyperinnervation after infarction,
      probably through an endothelin-1-depedent pathway. Chronic administration of E2
      after infarction may attenuate the arrhythmogenic response to programmed
      electrical stimulation.

PMID- 18048500
TI  - Expression and biological activity of parathyroid hormone-related peptide in
      pregnant rat uterine artery: any role for 8-iso-prostaglandin F2alpha?
AB  - PTHrP is produced in vessels and acts as a local modulator of tone. We recently
      reported that PTHrP(1-34) is able to induce vasorelaxation in rat uterine
      arteries, but in pregnancy, this response is blunted and becomes strictly
      endothelium dependent. The present study aimed to get insights into the
      mechanisms involved in these changes because the adaptation of uterine blood flow
      is essential for fetal development. On d 20 of gestation, RT-PCR analysis of
      uterine arteries showed that PTH/PTHrP receptor (PTH1R) mRNA expression was
      decreased, whereas that of PTHrP mRNA was increased. This was associated with a
      redistribution of the PTHrP/PTH1R system, with both PTH1R protein and PTHrP
      peptide becoming concentrated in the intimal layer of arteries from pregnant
      rats. On the other hand, the blunted vasorelaxation induced by PTHrP(1-34) in
      uterine arteries from pregnant rats was specifically restored by indomethacin and
      a specific cyclooxygenase-2 inhibitor, NS 398. This was associated with an
      increase in cyclooxygenase-2 expression and in 8-iso-prostaglandin F(2alpha)
      release when uterine arteries from pregnant rats were exposed to high levels of
      PTHrP(1-34). Most interestingly, 8-iso-prostaglandin F(2alpha) itself was able to
      increase PTHrP expression and reduce PTH1R expression in cultured rat aortic
      smooth muscle cells. These results suggest a local regulation of uterine artery
      functions by PTHrP during pregnancy resulting from PTH1R redistribution.
      Moreover, they shed light on a potential role of 8-iso-prostaglandin F(2alpha).

PMID- 18048499
TI  - Inflammatory status influences aromatase and steroid receptor expression in
      endometriosis.
AB  - Aberrant up-regulation of aromatase in eutopic endometrium and implants from
      women with endometriosis has been reported. Aromatase induction may be mediated
      by increased cyclooxygenase-2 (COX-2). Recently, we demonstrated that
      progesterone receptor (PR)-A and PR-B serve an antiinflammatory role in the
      uterus by antagonizing nuclear factor kappaB activation and COX-2 expression. PR
      C, which antagonizes PR-B, is up-regulated by inflammation. Although estrogen
      receptor alpha (ERalpha) is implicated in endometriosis, an antiinflammatory role
      of ERbeta has been suggested. We examined stage-specific expression of aromatase,
      COX-2, ER, and PR isoform expression in eutopic endometrium, implants,
      peritoneum, and endometrioma samples from endometriosis patients. Endometrial and
      peritoneal biopsies were obtained from unaffected women and those with fibroids.
      Aromatase expression in eutopic endometrium from endometriosis patients was
      significantly increased compared with controls. Aromatase expression in
      endometriosis implants was markedly increased compared with eutopic endometrium.
      Aromatase mRNA levels were increased significantly in red implants relative to
      black implants and endometrioma cyst capsule. Moreover, COX-2 expression was
      increased in implants and in eutopic endometrium of women with endometriosis as
      compared with control endometrium. As observed for aromatase mRNA, the highest
      levels of COX-2 mRNA were found in red implants. The ratio of ERbeta/ERalpha mRNA
      was significantly elevated in endometriomas compared with endometriosis implants
      and eutopic endometrium. Expression of PR-C mRNA relative to PR-A and PR-B mRNA
      was significantly increased in endometriomas compared with eutopic and control
      endometrium. PR-A protein was barely detectable in endometriomas. Thus, whereas
      PR-C may enhance disease progression, up-regulation of ERbeta may play an
      antiinflammatory and opposing role.

PMID- 18048501
TI  - Conditional expression of a Gi-coupled receptor in osteoblasts results in
      trabecular osteopenia.
AB  - G protein-coupled receptors (GPCRs) coupled to activation of Gs, such as the PTH1
      receptor (PTH1R), have long been known to regulate skeletal function and
      homeostasis. However, the role of GPCRs coupled to other G proteins such as Gi is
      not well established. We used the tet-off system to regulate the expression of an
      activated Gi-coupled GPCR (Ro1) in osteoblasts in vivo. Skeletal phenotypes were
      assessed in mice expressing Ro1 from conception, from late stages of
      embryogenesis, and after weaning. Long bones were assessed histologically and by
      microcomputed tomography. Expression of Ro1 from conception resulted in neonatal
      lethality that was associated with reduced bone mineralization. Expression of Ro1
      starting at late embryogenesis resulted in a severe trabecular bone deficit at 12
      wk of age (>51% reduction in trabecular bone volume fraction in the proximal
      tibia compared with sex-matched control littermates; n = 11; P < 0.01). Ro1
      expression for 8 wk beginning at 4 wk of age resulted in a more than 20%
      reduction in trabecular bone volume fraction compared with sex-matched control
      littermates (n = 16; P < 0.01). Bone histomorphometry revealed that Ro1
      expression is associated with reduced rates of bone formation and mineral
      apposition without a significant change in osteoblast or osteoclast surface. Our
      results indicate that signaling by a Gi-coupled GPCR in osteoblasts leads to
      osteopenia resulting from a reduction in trabecular bone formation. The severity
      of the phenotype is related to the timing and duration of Ro1 expression during
      growth and development. The skeletal phenotype in Ro1 mice bears some similarity
      to that produced by knockout of Gs-alpha expression in osteoblasts and thus may
      be due at least in part to Gi-mediated inhibition of adenylyl cyclase.

PMID- 18048502
TI  - Derlin-1 and p97/valosin-containing protein mediate the endoplasmic reticulum
      associated degradation of human V2 vasopressin receptors.
AB  - The endoplasmic reticulum-associated degradation (ERAD), the main quality control
      pathway of the cell, is crucial for the elimination of unfolded or misfolded
      proteins. Several diseases are associated with the retention of misfolded
      proteins in the early secretory pathway. Among them is X-linked nephrogenic
      diabetes insipidus, caused by mutations in the gene encoding the V2 vasopressin
      receptor (V2R). We studied the degradation pathways of three intracellularly
      retained V2R mutants with different misfolded domains in human embryonic kidney
      293 cells. At steady state, the wild-type V2R and the complex-glycosylated mutant
      G201D were partially located in lysosomes, whereas core-glycosylated mutants L62P
      and V226E were excluded from this compartment. In pulse-chase experiments,
      proteasomal inhibition stabilized the nonglycosylated and core-glycosylated forms
      of all studied receptors. In addition, all mutants and the wild-type receptor
      were found to be polyubiquitinylated. Nonglycosylated and core-glycosylated
      receptor forms were located in cytosolic and membrane fractions, respectively,
      confirming the deglycosylation and retrotranslocation of ERAD substrates to the
      cytosol. Distinct Derlin-1-dependent and -independent ERAD pathways have been
      proposed for proteins with different misfolded domains (cytosolic, extracellular,
      and membrane) in yeast. Here, we show for the first time that V2R mutants with
      different misfolded domains are able to coprecipitate the ERAD components
      p97/valosin-containing protein, Derlin-1 and the 26S proteasome regulatory
      subunit 7. Our results demonstrate the presence of a Derlin-1-mediated ERAD
      pathway degrading wild-type and disease-causing V2R mutants with different
      misfolded domains in a mammalian system.

PMID- 18048503
TI  - Recognising and responding to acute illness in patients in hospital.

PMID- 18048504
TI  - Six year audit of cardiac arrests and medical emergency team calls in an
      Australian outer metropolitan teaching hospital.
AB  - PROBLEM: In-hospital cardiac arrest often represents failure of optimal clinical
      care. The use of medical emergency teams to prevent such events is controversial.
      In-hospital cardiac arrests have been reduced in several single centre historical
      control studies, but the only randomised prospective study showed no such
      benefit. In our hospital an important problem was failure to call the medical
      emergency team or cardiac arrest team when, before in-hospital cardiac arrest,
      patients had fulfilled the criteria for calling the team. DESIGN: Single centre,
      prospective audit of cardiac arrests and data on use of the medical emergency
      team during 2000 to 2005. SETTING: 400 bed general outer suburban metropolitan
      teaching hospital. STRATEGIES FOR CHANGE: Three initiatives in the hospital to
      improve use of the medical emergency team: orientation programme for first year
      doctors, professional development course for medical registrars, and the evolving
      role of liaison intensive care unit nurses. KEY MEASURES FOR IMPROVEMENT:
      Incidence of cardiac arrests. EFFECTS OF THE CHANGE: Incidence of cardiac arrests
      decreased 24% per year, from 2.4/1000 admissions in 2000 to 0.66/1000 admissions
      in 2005. LESSONS LEARNT: Medical emergency teams can be efficacious when
      supported with a multidisciplinary, multifaceted education system for clinical
      staff.

PMID- 18048505
TI  - Doctors and climate change.

PMID- 18048506
TI  - Colectomy and IBD. Does surgery improve survival?

PMID- 18048507
TI  - Asylum seekers' access to care. Document is worrying.

PMID- 18048508
TI  - Community acquired pneumonia: Antibiotic coverage is atypical: evidence from
      randomised trials.

PMID- 18048509
TI  - Acute bronchiolitis. There may be a treatment.

PMID- 18048510
TI  - Acute bronchiolitis: Risk of hyponatraemia.

PMID- 18048511
TI  - Climate change and health. We must all act now.

PMID- 18048513
TI  - Former UN envoy attacks UNAIDS for its "catatonic passivity".

PMID- 18048512
TI  - Foreign doctors' victory: British benevolence and betrayal.

PMID- 18048514
TI  - Drug companies are ignoring health crisis in poor countries, Oxfam says.

PMID- 18048515
TI  - Scientists "reprogramme" skin cells to create embryonic stem cells.

PMID- 18048516
TI  - More than four in 10 women were not offered the choice of a home birth, report
      says.

PMID- 18048517
TI  - Diabetes expert accuses drug company of "intimidation".

PMID- 18048519
TI  - Stringent constraints on use of patients' data are harming research.

PMID- 18048520
TI  - Targeted screening may be a cost effective way to detect glaucoma.

PMID- 18048523
TI  - Studies of environmental causes of disease need to be more rigorous, leading
      scientists say.

PMID- 18048524
TI  - UN conference on climate change will test countries' commitment to public health.

PMID- 18048525
TI  - A third of people in UK with HIV don't know they are infected.

PMID- 18048526
TI  - Israel is set to outlaw trafficking in human organs.

PMID- 18048528
TI  - Cocaine use rises in Europe while overall drug use levels out.

PMID- 18048535
TI  - Counterfeit medicines. Bitter pills.

PMID- 18048536
TI  - Learning the second way.

PMID- 18048537
TI  - Behold the Christmas miracle of antioxidants.

PMID- 18048538
TI  - Thalidomide--the drama continues.

PMID- 18048539
TI  - Competition in a publicly funded healthcare system.

PMID- 18048540
TI  - Future of quality measurement.

PMID- 18048541
TI  - Vaginal discharge.

PMID- 18048542
TI  - Pemphigus vulgaris.

PMID- 18048543
TI  - Alcohol hand rubs: hygiene and hazard.

PMID- 18048550
TI  - Postdischarge follow-up: research and practice disconnect.

PMID- 18048551
TI  - Smoking rates among adolescents in substance abuse treatment programs.

PMID- 18048549
TI  - Focus groups of Alaska Native adolescent tobacco users: preferences for tobacco
      cessation interventions and barriers to participation.
AB  - Tobacco cessation interventions developed for Alaska Native adolescents do not
      exist. This study employed focus group methodology to explore preferences for
      tobacco cessation interventions and barriers to participation among 49 Alaska
      Natives (61% female) with a mean age of 14.6 (SD = 1.6) who resided in western
      Alaska. Using content analysis, themes from the 12 focus groups were found to be
      consistent across village, gender, and age groups. Program location or site
      (e.g., away from the village, hunting, fishing), a group-based format, and
      inclusion of medication and personal stories were reported to be important
      attributes of cessation programs. Motivators to quit tobacco were the perceived
      adverse health effects of tobacco, improved self-image and appearance, and the
      potential to be a future role model as a non-tobacco user for family and friends.
      Parents were perceived as potentially supportive to the adolescent in quitting
      tobacco. The findings will be used to develop tobacco cessation programs for
      Alaska Native youth.

PMID- 18048552
TI  - "We never used to do things this way": behavioral health care reform in New
      Mexico.
AB  - This column describes the first year of efforts in New Mexico to reform the
      behavioral health system. The process, guided by principles of cultural exchange
      theory, seeks to establish a "collaborative culture" among all stakeholders
      involved, including state agencies, consumers, families, advocates, and
      providers. Challenges have included inadequate system funding; insufficient
      development of skill sets among state personnel; underestimation of time and
      labor needed to address complex tasks; varying federal statutory and funder
      requirements for individual agencies; lack of a solid infrastructure for data
      collection, management, and dissemination; and clear definitions of the roles and
      relationships of local stakeholders to the state leadership group.

PMID- 18048553
TI  - Measuring trends in mental health care disparities, 2000 2004.
AB  - OBJECTIVE: This study measured trends in disparities in mental health care by use
      of an improved method that applies the Institute of Medicine (IOM) definition of
      racial-ethnic disparities. METHODS: Data from the 2000-2001 and 2003-2004 Medical
      Expenditure Panel Surveys were used to estimate trends in two global measures of
      racial-ethnic disparities in mental health care: having any mental health visit
      and total mental health care expenditure in the past year. Disparities between
      African Americans, Hispanics, and white Americans were examined by applying a new
      methodology based on the IOM definition of racial disparity that adjusts for
      health status and allows for mediation of racial-ethnic disparities through
      socioeconomic factors. Results found by use of this measure are contrasted with
      unadjusted means. RESULTS: African-American-white and Hispanic-white disparities
      in any use of mental health care worsened from 2000-2001 to 2003-2004 when the
      IOM definition was used; however, these trends were not evident in the unadjusted
      comparison. No significant African-American-white disparities were found in total
      mental health expenditures. Hispanic-white disparities in total mental health
      expenditures were significant within each time period and increased between 2000
      2001 and 2003-2004. CONCLUSIONS: The mental health care system continues to
      provide less care to persons in African-American and Hispanic minority groups
      than to whites, suggesting the need for policy initiatives to improve services
      for these minority groups. Future efforts at identifying trends in disparities in
      mental health services should use methodologies that adjust for health status and
      allow socioeconomic factors to mediate differences.

PMID- 18048554
TI  - Ethnocultural variations in mental illness discourse: some implications for
      building therapeutic alliances.
AB  - OBJECTIVE: In the delivery of mental health services over the past decade, the
      field has attempted to shift from paternalism to client-centered care, in which
      treatment and recovery are based on client-practitioner collaboration. Such a
      shift requires that providers elicit and work with clients' discursive accounts
      of their illness experiences and understand these accounts in the context of
      clients' ethnocultural backgrounds. The purpose of this ethnography was to
      elucidate ethnocultural aspects of illness accounts and interactions with the
      mental health system. METHODS: Over 18 months, 25 ethnically diverse, unemployed,
      inner-city residents with severe and long-term mental disorders participated in
      an ethnographic (participant observation) study of illness accounts and their
      relationship to sociocultural background. Field ethnographers shared in
      activities with participants at many of their regular haunts, engaging in
      observation, conversation, and informal interviewing in many real-world contexts
      and settings. RESULTS: The study revealed significant differences between the
      ways that European Americans, African Americans, and Puerto Rican Americans
      discursively constructed their illness experiences and their interactions with
      the mental health system. The clients' narratives of their illness experiences
      provided valuable information, which clinicians could use to open up topics for
      discussion, insert themselves into an engaging relationship with clients, and
      link clinical advice or guidance with the clients' own conceptions of how mental
      illness fits into their larger lived world. CONCLUSIONS: To develop a working
      therapeutic partnership with clients, mental health service providers must become
      aware through context-sensitive, context-informed dialog of the differences in
      how individual clients "en-story," communicate, and experience their illnesses.

PMID- 18048555
TI  - Does stigma keep poor young immigrant and U.S.-born Black and Latina women from
      seeking mental health care?
AB  - OBJECTIVE: This study examined the extent to which stigma-related concerns about
      mental health care account for the underuse of mental health services among low
      income immigrant and U.S.-born black and Latina women. METHODS: Participants
      included 15,383 low-income women screened for depression in county entitlement
      services who were asked about barriers to care, stigma-related concerns, and
      whether they wanted or were getting mental health care. RESULTS: Among those who
      were depressed, compared with U.S.-born white women, each of the black groups
      were more likely to report stigma concerns (African immigrants, odds ratio
      [OR]=3.28, p=.004; Caribbean immigrants, OR=6.17, p=.005; U.S.-born blacks,
      OR=6.17, p=.06). Compared with U.S.-born white women, immigrant African women
      (OR=.18, p<.001), immigrant Caribbean women (OR=.11, p=.001), U.S.-born black
      women (OR=.31, p<.001), and U.S.-born Latinas (OR=.32, p=.03) were less likely to
      want treatment. Conversely, compared with U.S.-born white women, immigrant
      Latinas (OR=2.17, p=.02) were more likely to want treatment. There was a
      significant stigma-by-immigrant interaction predicting interest in treatment
      (p<.001). Stigma reduced the desire for mental health treatment for immigrant
      women with depression (OR=.35, p<.001) to a greater extent than it did for U.S.
      born white women with depression (OR=.52, p=.24). CONCLUSIONS: Stigma-related
      concerns are most common among immigrant women and may partly account for
      underutilization of mental health care services by disadvantaged women from
      ethnic minority groups.

PMID- 18048556
TI  - Initiation and use of public mental health services by persons with severe mental
      illness and limited english proficiency.
AB  - OBJECTIVE: Few studies have examined the effect of limited English proficiency on
      use of mental health services by persons with mental illness from ethnic minority
      groups who are uninsured or publicly insured. This study examined how indigent or
      publicly insured Latino and Asian adults with limited English proficiency
      initially accessed the public mental health system and how their use of services
      changed over time compared with English-proficient peers. METHODS: Data from San
      Diego County for fiscal years 2000-2005 were used to examine point of first
      contact and use of inpatient, emergency, and outpatient services in the 18
      subsequent months among 9,243 clients with a psychiatric diagnosis of
      schizophrenia, bipolar disorder, or major depression. Multivariate regression
      models were used to compute standardized estimates of utilization. RESULTS:
      Latino and Asian clients with limited English proficiency were significantly less
      likely to first access the system through emergency services and more likely to
      access the system through outpatient services (p<.001 for each comparison). In
      two outpatient programs that were focused on delivering services to clients with
      limited English proficiency, clients had a higher intensity of outpatient service
      use than clients in clinics that did not have such a focus (p<.05 for each).
      CONCLUSIONS: The initial pattern of service use was favorable for both groups.
      However, over time this pattern persisted for Asian clients with limited English
      proficiency but not for Latino clients with limited English proficiency. Findings
      suggest that ethnically focused programs may be an effective approach to engaging
      populations that are underrepresented in the mental health system.

PMID- 18048557
TI  - Predictors of timely follow-up care among medicaid-enrolled adults after
      psychiatric hospitalization.
AB  - OBJECTIVE: This study examined whether predictors of timely follow-up care after
      inpatient psychiatric discharge in non-Medicaid populations also predicted timely
      follow-up care among Medicaid-enrolled adults. METHODS: The study examined the
      rates of seven- and 30-day follow-up care for 6,730 Medicaid-enrolled adults
      discharged from inpatient psychiatric facilities during 2004 and 2005 by using
      claims data from the largest Medicaid managed behavioral health organization in a
      large mid-Atlantic state. The relationship between predictor variables and timely
      aftercare was examined by using multiple logistic regression. RESULTS: Thirty
      percent of individuals received follow-up care within seven days, and 49%
      received follow-up care within 30 days. After the analysis controlled for age and
      gender, those receiving clinical services in the 30 days before hospitalization
      were significantly more likely to receive follow-up care within seven days (odds
      ratio [OR]=3.59, 95% confidence interval [CI]=3.20-4.03) than individuals with
      longer inpatient stays (ten or more days) (OR=1.34, CI=1.15-1.57) and individuals
      from urban communities (OR=1.18, CI=1.05-1.34). African Americans (OR=.69, CI=.60
      .78), individuals with co-occurring behavioral health and substance use disorders
      (OR=.78, CI=.68-.89), individuals involuntarily admitted (OR=.79, CI=.68-.91),
      and individuals discharged against medical advice (OR=.59, CI=.39-.87) were
      significantly less likely than their comparison groups to receive follow-up care
      within seven days. Thirty-day follow-up care results were similar. CONCLUSIONS:
      Patient sociodemographic, clinical, and service utilization characteristics
      predicted timely follow-up care. Efforts to improve follow-up care utilization
      should target higher-risk individuals while developing and evaluating
      interventions to address specific barriers in these groups.

PMID- 18048558
TI  - Service use and cost in 2002 among clients in community settings who were
      discharged from a state hospital in 1989.
AB  - OBJECTIVE: This analysis is a follow-up of a 1992 study of service use and cost
      of care among patients discharged from a state hospital. This study documented
      utilization and cost of care in 2002. METHODS: Study participants were 150 former
      long-stay patients who were discharged from a state psychiatric hospital in 1989.
      An integrated database of all mental health and medical services reimbursed by
      Medicaid and Medicare as well as state- and county-funded services was used to
      construct descriptive statistics on service use and unit cost measures. Data on
      mortality, homelessness and criminal arrests were obtained from vital statistics,
      jail records and shelter admissions. RESULTS: During 2002, 18% of study
      participants had a psychiatric hospital admission, with a mean length of stay of
      60 days. Almost all participants (99%) received some form of outpatient mental
      health care, and 66% were living in publicly funded residential housing. The
      total annual cost per study participant for the 2002 service package was $89,699.
      Residential care accounted for 54% of the total cost. Between 1989 and 2005, 3%
      were admitted to county jails and 9% had experienced homelessness. Of the
      original discharged sample of 590 patients, 37% died between 1989 and 2002; the
      mean age at death was 63+/-15 years. CONCLUSIONS: This analysis suggests that
      individuals discharged from state psychiatric institutions have been integrated
      into community residential settings and are receiving psychiatric outpatient
      treatment on a regular basis. Cost estimates, using the consumer price index for
      2002, were $78,773 in 1992 compared with $85,850 for the exact same service
      package in 2002.

PMID- 18048559
TI  - Critical time intervention for reentry from prison for persons with mental
      illness.
AB  - Critical time intervention (CTI) is a nine-month, three-stage intervention that
      strategically develops individualized linkages in the community and seeks to
      enhance engagement with treatment and community supports through building problem
      solving skills, motivational coaching, and advocacy with community agencies. It
      is an empirically supported practice shown to enhance continuity of care for
      people with mental illness after discharge from homeless shelters and psychiatric
      hospitals. This article describes CTI as a promising model to provide support for
      reentry from prison for people with mental illness. A conceptual model is
      presented for evaluating the impact of CTI on the transition from correctional
      settings to the community. The model is potentially useful for further
      development of mental health service-driven models of reentry process and
      outcome. Although CTI is a potentially useful model for reentry services for this
      population, challenges remain in adapting it to specific correctional facilities,
      justice systems, and community contexts.

PMID- 18048560
TI  - Horizons of context: understanding the police decision to arrest people with
      mental illness.
AB  - The criminalization hypothesis assumes that deinstitutionalization coupled with
      inadequate police training has led to the increased arrest of people with mental
      illness. Arrest is viewed as a means to manage the troublesome behavior that
      often results from mental illness. Supporting research has emphasized the
      contributing role that illness plays in the arrest decision. This assumption
      largely ignores an extant criminal justice literature on the factors that
      influence arrest. On the basis of a review of this criminal justice literature,
      beginning with Bittner's 1967 seminal work, a framework is proposed that
      incorporates three contexts -- manipulative, temporal, and scenic -- surrounding
      the police encounter and the relationship of these contexts to mental illness.
      These three "horizons" incorporate the characteristics of the community, the
      offender, and the incident, all of which are recognized as influential in shaping
      police discretion. The scenic horizon is indicative of the features of the
      community. The temporal horizon includes police knowledge that stretches beyond
      the specific incident and officer characteristics. The manipulative horizon
      involves the current incident from the standpoint of the officer and includes
      considerations of safety for the community as well as the immediate concerns of
      the officer. Implications of this framework are then explored with respect to
      both police and mental health service mandates.

PMID- 18048561
TI  - Cultural competence, evidence-based medicine, and evidence-based practices.
AB  - Cultural competence and evidence-based medicine are two powerful discourses that
      have become core components of contemporary psychiatry. Evidence-based medicine
      has particularly influenced psychiatry by spawning the enthusiastic creation and
      adoption of evidence-based practices. Despite their prominence, these paradigms
      have stood somewhat in isolation from each other. This Open Forum explores the
      relationship between these two conceptual paradigms, paying particular attention
      to implications for evidence-based practices. The author aims to stimulate a
      greater degree of mutual engagement and integration of these paradigms by
      examining epistemological, philosophical, and methodological overlap and
      discrepancy. Both paradigms can stretch and enrich each other in a positive
      manner. This could help achieve a situation where cultural competency becomes
      more evidence based and evidence-based medicine becomes more culturally
      competent. Such action would help bring to fruition a shared aim of both
      discourses-more humane, just, and effective patient-centered care.

PMID- 18048562
TI  - A qualitative analysis of the perception of stigma among Latinos receiving
      antidepressants.
AB  - OBJECTIVE: This study sought to describe the role of stigma in antidepressant
      adherence among Latinos. METHODS: The study utilized data generated from six
      focus groups of Latino outpatients receiving antidepressants (N=30). By using a
      grounded theory approach, qualitative analysis focused specifically on the role
      of stigma in antidepressant treatment, as well as salient Latino values. RESULTS:
      Perceptions of stigma were related to both the diagnosis of depression and use of
      antidepressant medication. Qualitative analyses showed that antidepressant use
      was seen as implying more severe illness, weakness or failure to cope with
      problems, and being under the effects of a drug. Reports of stigma were also
      related to social consequences. Also, the perceived negative attributes of
      antidepressant use were at odds with self-perceived cultural values. CONCLUSIONS:
      Stigma was a prominent concern among Latinos receiving antidepressants, and
      stigma often affected adherence. Furthermore, culture is likely to play an
      important role in the communication of stigma and its associated complications.

PMID- 18048563
TI  - Utilization of mental health treatment and other services by battered women in
      shelters.
AB  - OBJECTIVE: This study investigated the frequency and types of resources used by
      battered women in shelters, as well as factors that relate to greater use of
      mental health services and to seeking help from a greater number of resources.
      METHODS: A total of 164 African-American (N=94) and white (N=70) battered women
      in two shelters were examined by using a series of clinical interviews and self
      report measures that assessed posttraumatic stress disorder and other axis I
      pathology, mental health treatment and other service use, abuse severity, and
      lifetime trauma prevalence. RESULTS: Results suggest that few of the women used
      available resources, especially mental health treatment, with African-American
      women less likely to use mental health treatment and criminal justice
      interventions. Additionally, possession of medical insurance and a greater number
      of types of prior trauma were significantly associated with greater help seeking.
      CONCLUSIONS: Findings highlight the need for identifying barriers to battered
      women's access to resources, as well as the importance of assisting them in
      obtaining medical coverage.

PMID- 18048564
TI  - Revalidating the brief jail mental health screen to increase accuracy for women.
AB  - OBJECTIVE: Jails need a reliable tool to identify inmates who require further
      mental health assessment and treatment. This research attempted to revalidate the
      Brief Jail Mental Health Screen (BJMHS) as such a tool. This research added four
      items to the original eight-item screen (BJMHS-R), targeting depression and
      trauma to improve performance of the screen with women. METHODS: BJMHS-R data
      were collected in four jails from 10,258 detainees. A subset of 464 were
      administered the Structured Clinical Interview for DSM-IV (SCID) for cross
      validation. RESULTS: The original BJMHS outperformed the revised screen. The
      original correctly classified 80% of males and 72% of females on the basis of
      SCID diagnoses, compared with classification rates of 72% and 66%, respectively,
      with the BJMHS-R. Overall, the BJMHS identified 16% of screened detainees as
      needing referral for further assessment, whereas the BJMHS-R identified 22%.
      CONCLUSIONS: The original eight-item BJMHS is a practical, efficient tool for
      intake screening by jail correction officers of male and female detainees.

PMID- 18048565
TI  - Routine laboratory screening among newly admitted psychiatric patients: is it
      worthwhile?
AB  - OBJECTIVE: This study compared the prevalence of abnormal results of laboratory
      tests routinely performed among newly hospitalized psychiatric patients in Spain
      and the cost-effectiveness of such tests. METHODS: Routine biochemical tests were
      performed for 510 newly hospitalized psychiatric patients. For all tests, this
      study examined the prevalence of values outside the normal range and compared the
      number needed to screen to find one abnormal result (NNSAR=1/prevalence of
      abnormal results in the studied population) with the direct cost spent to find
      one abnormal result (DCSAR=NNSAR x direct cost per test). RESULTS: The prevalence
      of values outside the normal range ranged from 1% for free thyroxine (FT4) to 36%
      for total cholesterol. The NNSAR ranged from 2.8 for total cholesterol to 127.3
      for FT4. The DCSAR ranged from .38 international dollars of 2000 (I$) for
      chloride to 402.27 I$ for FT4. CONCLUSIONS: There were large differences in the
      prevalence of abnormal results (NNSAR) and cost-effectiveness (DCSAR) for the
      laboratory tests routinely performed among newly admitted psychiatric patients.

PMID- 18048566
TI  - States' priorities for persons with mental illness in the criminal justice
      system.

PMID- 18048567
TI  - The ten commandments of services research.

PMID- 18048568
TI  - Origins of the quadrant model for persons with co-occurring disorders.

PMID- 18048571
TI  - The effects of population-based faecal occult blood test screening upon emergency
      colorectal cancer admissions in Coventry and north Warwickshire.
AB  - OBJECTIVE: The English arm of the UK Bowel Cancer Screening Pilot has recently
      concluded its third round. The primary aim of this study was to assess the
      effects of this programme on the emergency and elective cancer workload at
      University Hospitals Coventry and Warwickshire NHS Trust; the largest trust
      within the screened region. The secondary aim was to assess its effect upon Dukes
      staging, mortality and stoma formation for emergency colorectal cancer (CRC)
      admissions. DESIGN: A retrospective analysis of validated data for CRC admissions
      over a period of 6 years from 1999 to 2004 was performed. The first year, 1999,
      represented the pre-screening year (PSY) which was taken as a baseline. Data for
      the next 5 years, screening years 1-5 (SY1-SY5), were recorded for the mode of
      admission, occurrence of emergency surgery, 30-day mortality and Dukes staging.
      RESULTS: In the PSY (1999), 29.4% of CRCs were admitted as an emergency,
      decreasing to 15.8% by 2004 (p = 0.001). As a consequence, there was a
      significant decrease in the number of emergency CRC procedures performed over the
      same period (p<0.05). There was also a significant reduction in the 30-day
      mortality from 48% in 1999 to 13% in 2004 (p<0.05). Dukes stage C carcinomas,
      however, remained the predominant stage presenting as emergencies throughout the
      studied period (SY3, 53%; SY4, 38%; SY5, 50%). CONCLUSION: Following commencement
      of the UK Bowel Cancer Screening Pilot, there has been a significant decline in
      emergency CRC workload with a marked improvement in 30-day mortality and
      decreased stoma formation, in Coventry and North Warwickshire. It is postulated
      that the witnessed and notable positive impact over such a short time period is
      the result of increased detection of asymptomatic malignancies within the
      screening programme, increased public awareness of the symptoms of CRC, together
      with a change in attitudes and referral patterns of general practitioners within
      Coventry and North Warwickshire.

PMID- 18048572
TI  - Pharmacokinetics and pharmacodynamics of oral heparin solid dosage form in
      healthy human subjects.
AB  - The present investigation determined the molecular structure and the
      pharmacokinetic and pharmacodynamic profiles of oral unfractionated heparin
      containing oral absorption enhancer sodium N-[8-(2-hydroxybenzoyl)
      amino]caprylate, salcaprozate sodium (SNAC) and assessed the safety and
      tolerability of the orally dosed heparin solid dosage form versus other routes.
      Sixteen healthy men were included in this single-dose, 3-way crossover,
      randomized, open-label study. Disaccharide compositional analysis was performed
      using capillary high-performance liquid chromatography with electrospray
      ionization mass spectrometry detection. The pharmacodynamics of heparin were
      obtained from analysis of plasma anti-factor Xa, anti-factor IIa, activated
      partial thromboplastin time, and total tissue factor pathway inhibitor data. The
      molecular weight properties and the disaccharide composition of orally
      administered unfractionated heparin/SNAC and parenterally administered
      unfractionated heparin are identical and consistent with the starting
      pharmaceutical standard heparin. Furthermore, the anti-factor Xa/anti-factor IIa
      ratio achieved is of approximately 1:1. This is the first true pharmacokinetic
      study to measure the chemical compositions of heparin administered by different
      routes.

PMID- 18048573
TI  - Effect of high-dose metronidazole on pharmacokinetics of oral budesonide and vice
      versa: a double drug interaction study.
AB  - Recent case reports suggest that addition of high-dose metronidazole might be
      associated with elevated plasma concentrations of substrates of cytochrome P450
      (CYP) 3A. Because patients with fistulizing Crohn's disease benefit by using high
      doses of metronidazole for prolonged periods, this study's primary aim was to
      evaluate the effect of high-dose metronidazole on the pharmacokinetics of oral
      budesonide, a sensitive substrate of CYP3A commonly prescribed in acute
      inflammatory bowel disease. Twelve healthy adults received 1.5 g metronidazole
      per day over 1 week. The CYP3A-dependent metabolic profile of an oral dose of
      budesonide (3 mg) and that of endogenous cortisol were compared intraindividually
      before and after administration of metronidazole. There was neither a significant
      effect of high-dose metronidazole on the area under the plasma concentration-time
      curve (AUC) of budesonide (90% confidence interval, 79%-115%) nor on the AUC
      ratios of 6beta-hydroxybudesonide/budesonide and 16alpha
      hydroxyprednisolone/budesonide. In parallel, metronidazole did not significantly
      alter formation of 6beta-hydroxycortisol. Vice versa, budesonide did not affect
      the AUC of metronidazole (90% confidence interval, 91%-100%). The authors
      conclude that in contrast to concomitant intake of other imidazoles such as
      ketoconazole, concomitant intake of metronidazole may not lead to serious safety
      concerns due to elevated systemic concentrations of the glucocorticoid
      budesonide.

PMID- 18048574
TI  - A randomized, placebo-controlled trial to evaluate the efficacy, safety, and
      pharmacodynamic interaction of coadministered amlodipine and atorvastatin in 1660
      patients with concomitant hypertension and dyslipidemia: the respond trial.
AB  - Guidelines stress the importance of the simultaneous management of multiple
      cardiovascular risk factors. This can in part be achieved by coadministration of
      lipid-lowering and antihypertensive treatments. Potential pharmacodynamic
      interaction between drugs should be investigated as part of developing single
      pill combinations. The Respond trial assessed whether combining amlodipine to
      treat hypertension and atorvastatin to treat dyslipidemia affected the action of
      either monotherapy. A total of 1660 hypertensive patients with dyslipidemia
      received 1 of 15 combinations of amlodipine (placebo, 5, or 10 mg) and
      atorvastatin (placebo, 10, 20, 40, or 80 mg) in a 3 x 5 factorial randomized,
      placebo-controlled design. At 8 weeks, combination-treated patients experienced
      dose-related and statistically significant reductions in systolic blood pressure,
      low-density lipoprotein cholesterol, and Framingham risk score. Overall,
      coadministered atorvastatin and amlodipine was well tolerated and without adverse
      pharmacodynamic interaction; combination treatment did not affect the low-density
      lipoprotein cholesterol-lowering efficacy and safety of atorvastatin, or the
      systolic blood pressure-lowering efficacy and safety of amlodipine.

PMID- 18048575
TI  - Antiretroviral drugs.
AB  - The first antiretroviral drug to be licensed, zidovudine, became available in
      1987. Until December 1995, the antiretroviral drugs available and approved for
      clinical use in the United States consisted of only 5 individual drugs belonging
      to a single class of antiretroviral agents, nucleoside analog reverse
      transcriptase inhibitors. Since then, numerous other antiretroviral drugs and
      classes of antiretroviral drugs have been introduced. Additional drugs and newer
      classes of antiretrovirals are in various stages of development. Currently, there
      are 22 Food and Drug Administration (FDA)-approved antiretroviral agents
      categorized in 4 classes of drugs: nucleoside/nucleotide analog reverse
      transcriptase inhibitors, nonnucleoside analog reverse transcriptase inhibitors,
      protease inhibitors, and fusion inhibitors. The authors review the general
      characteristics of each class of antiretroviral drugs, including mechanism of
      action, pharmacologic properties, adverse effects, and drug interactions. A
      synopsis of current antiretroviral treatment guidelines is also provided.

PMID- 18048576
TI  - Commentary on ACCP position statement on the use of microdosing in the drug
      development process.

PMID- 18048579
TI  - Internalization via Antennapedia protein transduction domain of an scFv antibody
      toward c-Myc protein.
AB  - We constructed a single-chain variable fragment miniantibody (G11-scFv) directed
      toward the transactivation domain of c-Myc, which is fused with the
      internalization domain Int of Antennapedia at its carboxyl terminus (a cargo
      carrier construct). In ELISA experiments, an EC(50) for binding saturation was
      achieved at concentrations of G11-scFv-Int(-) of approximately 10(-8) M.
      Internalization of a fluoresceinated Fl-G11-scFv-Int(+) construct was observed in
      intact human cultured cells with confocal microscopy. After 5 h of incubation in
      medium containing 1 microM Fl-G11-scFv-Int(+) or Fl-G11-scFv-Int(-), fluorescence
      intensity was determined in individual cells, both for cytoplasmic and nuclear
      compartments: concentration levels of Fl-G11-scFv-Int(+), relative to the
      extracellular culture medium concentration, were 4-5 times higher in the
      cytoplasm, 7-8 times higher in the nucleus, and 10 times higher in the nucleoli.
      In the same experimental conditions, the Fl-G11-scFv-Int(-) construct was 3-4
      times more concentrated outside of the cells than inside. Cell membranes kept
      their integrity after 5 h of incubation. The antiproliferative activity of our
      miniantibody was studied on HCT116 cells. Incubation with 4 microM G11-scFv
      Int(+) for 4 days induced very significant statistical and biological growth
      inhibition, whereas Int alone was completely inactive. Miniantibodies capable of
      penetrating cell membranes dramatically broaden the potential for innovative
      therapeutic agents and attack of new targets.

PMID- 18048580
TI  - Targeting multiple Alzheimer's disease etiologies with multimodal neuroprotective
      and neurorestorative iron chelators.
AB  - Dysregulation of brain iron homeostasis is central to early neuropathological
      events in Alzheimer's disease (AD), including oxidative stress, inflammatory
      processes, amyloid deposition, tau phosphorylation, and neuronal cell cycle
      regulatory failure, leading to apoptosis. Also, there is a direct link between
      iron metabolism and AD pathogenesis, demonstrated by the presence of an iron
      responsive element in the 5' UTR of the amyloid precursor protein transcript. As
      a consequence of these findings, a new paradigm is emerging that includes the
      development of iron-chelating neuroprotective-neurorescue drugs with multimodal
      functions, acting at various pathological brain targets. This concept is
      challenging the widely held assumption that "silver bullet" agents are superior
      to "dirty drugs" in drug therapy for neurodegenerative diseases. At best, the so
      called magic bullets exhibit moderate symptomatic activity without modifying the
      course of disease progression. The present review elaborates on conventional and
      novel therapeutic targets of various multifunctional iron-chelating drugs (e.g.,
      chemically designed compounds; natural polyphenols) that address multiple central
      nervous system etiologies in AD, aimed at preventing or slowing disease
      evolution. A similar approach in drug design is being investigated for treatment
      of cancer, AIDS, cardiovascular diseases, and depression.

PMID- 18048581
TI  - Chromosome 17 and 21 aneuploidy in buccal cells is increased with ageing and in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a premature ageing syndrome characterized by
      cognitive impairment arising from neuropathological changes occurring within
      specific areas of the brain. We report a 1.5-fold increase in trisomy 21 (P <
      0.001) and a 1.2-fold increase in trisomy 17 (P < 0.001) in buccal cells of
      Alzheimer's patients compared to age- and gender-matched controls. Chromosome 17
      and chromosome 21 monosomy and trisomy increase significantly with age (P <
      0.001). Down's syndrome, which exhibits similar neuropathological features to
      those observed in AD also showed a strong increase in chromosome 17 monosomy and
      trisomy compared to matched controls (P < 0.001). These results suggest that an
      increased incidence of aneusomy for both chromosomes 17 and 21 may contribute to
      the aetiology of AD. We also investigated aneuploidy rates in hippocampal brain
      cells, which have been shown to have a low rate of cell division, which may be
      relevant in potential incidence of non-disjunction. However, aneuploidy rate for
      chromosomes 17 and 21 in the nuclei of hippocampus cells of brains from
      Alzheimer's patients and controls were not significantly different. These results
      are suggestive that the aneuploidy events investigated which are increased beyond
      the incidence in normal ageing may be influenced by genetic factors that may
      predispose to AD, but are unlikely to be a primary cause of AD brain pathology.

PMID- 18048582
TI  - Biomechanics of overground vs. treadmill walking in healthy individuals.
AB  - The goal of this study was to compare treadmill walking with overground walking
      in healthy subjects with no known gait disorders. Nineteen subjects were tested,
      where each subject walked on a split-belt instrumented treadmill as well as over
      a smooth, flat surface. Comparisons between walking conditions were made for
      temporal gait parameters such as step length and cadence, leg kinematics, joint
      moments and powers, and muscle activity. Overall, very few differences were found
      in temporal gait parameters or leg kinematics between treadmill and overground
      walking. Conversely, sagittal plane joint moments were found to be quite
      different, where during treadmill walking trials, subjects demonstrated less
      dorsiflexor moments, less knee extensor moments, and greater hip extensor
      moments. Joint powers in the sagittal plane were found to be similar at the ankle
      but quite different at the knee and hip joints. Differences in muscle activity
      were observed between the two walking modalities, particularly in the tibialis
      anterior throughout stance, and in the hamstrings, vastus medialis and adductor
      longus during swing. While differences were observed in muscle activation
      patterns, joint moments and joint powers between the two walking modalities, the
      overall patterns in these behaviors were quite similar. From a therapeutic
      perspective, this suggests that training individuals with neurological injuries
      on a treadmill appears to be justified.

PMID- 18048583
TI  - The effect of intermittent hypobaric hypoxic exposure and sea level training on
      submaximal economy in well-trained swimmers and runners.
AB  - To evaluate the effect of intermittent hypobaric hypoxia combined with sea level
      training on exercise economy, 23 well-trained athletes (13 swimmers, 10 runners)
      were assigned to either hypobaric hypoxia (simulated altitude of 4,000-5,500 m)
      or normobaric normoxia (0-500 m) in a randomized, double-blind design. Both
      groups rested in a hypobaric chamber 3 h/day, 5 days/wk for 4 wk. Submaximal
      economy was measured twice before (Pre) and after (Post) the treatment period
      using sport-specific protocols. Economy was estimated both from the relationship
      between oxygen uptake (V(.-)o2) and speed, and from the absolute V(.-)o2 at each
      speed using sport-specific protocols. V(.-)o2 was measured during the last 60 s
      of each (3-4 min) stage using Douglas bags. Ventilation (V(.-)E), heart rate
      (HR), and capillary lactate concentration ([La(-)]) were measured during each
      stage. Velocity at maximal V(.-)o2 (velocity at V(.-)o2max) was used as a
      functional indicator of changes in economy. The average V(.-)o2 for a given speed
      of the Pre values was used for Post test comparison using a two-way, repeated
      measures ANOVA. Typical error of measurement of V(.-)o2 was 4.7% (95% confidence
      limits 3.6-7.1), 3.6% (2.8-5.4), and 4.2% (3.2-6.9) for speeds 1, 2, and 3,
      respectively. There was no change in economy within or between groups (ANOVA
      interaction P = 0.28, P = 0.23, and P = 0.93 for speeds 1, 2, and 3). No
      differences in submaximal HR, [La-], Ve, or velocity at V(.-)o2(max) were found
      between groups. It is concluded that 4 wk of intermittent hypobaric hypoxia did
      not improve submaximal economy in this group of well-trained athletes.

PMID- 18048584
TI  - Point: High-frequency ventilation is the optimal physiological approach to
      ventilate ARDS patients.

PMID- 18048585
TI  - Electrotonic remodeling following myocardial infarction in dogs susceptible and
      resistant to sudden cardiac death.
AB  - Passive electrical remodeling following myocardial infarction (MI) is well
      established. These changes can alter electrotonic loading and trigger the
      remodeling of repolarization currents, a potential mechanism for ventricular
      fibrillation (VF). However, little is known about the role of passive electrical
      markers as tools to identify VF susceptibility post-MI. This study investigated
      electrotonic remodeling in the post-MI ventricle, as measured by myocardial
      electrical impedance (MEI), in animals prone to and resistant to VF. MI was
      induced in dogs by a two-stage left anterior descending (LAD) coronary artery
      ligation. Before infarction, MEI electrodes were placed in remote (left
      circumflex, LCX) and infarcted (LAD) myocardium. MEI was measured in awake
      animals 1, 2, 7, and 21 days post-MI. Subsequently, VF susceptibility was tested
      by a 2-min LCX occlusion during exercise; 12 animals developed VF (susceptible,
      S) and 12 did not (resistant, R). The healing infarct had lower MEI than the
      normal myocardium. This difference was stable by day 2 post-MI (287 +/- 32 Omega
      vs. 425 +/- 62 Omega, P < 0.05). Significant differences were observed between
      resistant and susceptible animals 7 days post-MI; susceptible dogs had a wider
      electrotonic gradient between remote and infarcted myocardium (R: 89 +/- 60 Omega
      vs. S: 180 +/- 37 Omega). This difference increased over time in susceptible
      animals (252 +/- 53 Omega at 21 days) due to post-MI impedance changes on the
      remote myocardium. These data suggest that early electrotonic changes post-MI
      could be used to assess later arrhythmia susceptibility. In addition, passive
      electrical changes could be a mechanism driving active-electrical remodeling post
      MI, thereby facilitating the induction of arrhythmias.

PMID- 18048586
TI  - Anatomical and functional development of the pre-Botzinger complex in prenatal
      rodents.
AB  - Developmental anomalies of central respiratory neural control contribute to
      newborn mortality and morbidity. Elucidation of the cellular, molecular, trophic,
      and genetic mechanisms involved in the formation and function of respiratory
      nuclei during prenatal development will provide a foundation for understanding
      pathologies. The pre-Botzinger Complex (pre-BotC) is a specific group of neurons
      located in the ventrolateral medulla that is critical for respiratory
      rhythmogenesis. Thus it has become a major focus of research. Here, we provide an
      overview of current knowledge regarding the anatomical and functional emergence
      of the rodent pre-BotC during the prenatal period.

PMID- 18048587
TI  - Heritability of lumbar flexibility and the role of disc degeneration and body
      weight.
AB  - Spinal range of motion is evaluated in assessing patients with back problems and
      monitoring outcomes, as well as in general fitness assessments. Yet, determinants
      of the substantial interindividual variation in spinal range of motion are not
      well understood. Substantial genetic effects on global measures of range of
      motion and hypermobility have been suggested from earlier studies, but genetic
      influences specifically on spinal range of motion have not been previously
      studied. The objectives of the present study were to investigate the relative
      role of genetic and environmental influences on lumbar range of motion in adult
      men and the pathways through which genes may influence range of motion. Thus we
      conducted a classic twin study of 300 monozygotic and dizygotic male twin pairs
      with consideration of covariates, using standard statistical methods. All
      subjects underwent a clinical examination, including general anthropometrics,
      lumbar range of motion, and lumbar MRI to assess disc degeneration, as well as an
      extensive interview on environmental and behavioral exposures and back pain
      history. We found the proportion of variance in lumbar range of motion
      attributable to genetic influences (heritability estimate) to be 47%. The extent
      of lumbar range of motion in flexion was predominantly determined by genetic
      influences (64%), while extension was influenced to a somewhat greater degree by
      environmental and behavioral factors. Statistically significant age-adjusted
      genetic correlations were found between lumbar extension and disc degeneration
      variables (r(a) = -0.38 to -0.43) and between flexion and body weight (r(a) = 
      0.33), suggesting two pathways through which genes influence lumbar range of
      motion.

PMID- 18048588
TI  - Perspective on the future use of genomics in exercise prescription.

PMID- 18048589
TI  - Dynamic left ventricular elastance: a model for integrating cardiac muscle
      contraction into ventricular pressure-volume relationships.
AB  - To integrate myocardial contractile processes into left ventricular (LV)
      function, a mathematical model was built. Muscle fiber force was set equal to the
      product of stiffness and elastic distortion of stiffness elements, i.e., force
      bearing cross bridges (XB). Stiffness dynamics arose from recruitment of XB
      according to the kinetics of myofilament activation and fiber-length changes.
      Elastic distortion dynamics arose from XB cycling and the rate-of-change of fiber
      length. Muscle fiber stiffness and distortion dynamics were transformed into LV
      chamber elastance and volumetric distortion dynamics. LV pressure equaled the
      product of chamber elastance and volumetric distortion, just as muscle-fiber
      force equaled the product of muscle-fiber stiffness and lineal elastic
      distortion. Model validation was in terms of its ability to reproduce cycle-time
      dependent LV pressure response, DeltaP(t), to incremental step-like volume
      changes, DeltaV, in the isolated rat heart. All DeltaP(t), regardless of the time
      in the cycle at which DeltaP(t) was elicited, consisted of three phases: phase 1,
      concurrent with the leading edge of DeltaV; phase 2, a brief transient recovery
      from phase 1; and phase 3, sustained for the duration of systole. Each phase
      varied with the time in the cycle at which DeltaP(t) was elicited. When the model
      was fit to the data, cooperative activation was required to sustain systole for
      longer periods than was possible with Ca(2+) activation alone. The model
      successfully reproduced all major features of the measured DeltaP(t) responses,
      and thus serves as a credible indicator of the role of underlying contractile
      processes in LV function.

PMID- 18048591
TI  - Multichannel thin-film electrode for intramuscular electromyographic recordings.
AB  - It is currently not possible to record electromyographic (EMG) signals from many
      locations concurrently inside the muscle in a single wire electrode system. We
      developed a thin-film wire electrode system for multichannel intramuscular EMG
      recordings. The system was fabricated using a micromachining process, with a
      silicon wafer as production platform for polyimide-based electrodes. In the
      current prototype, the flexible polymer structure is 220 microm wide, 10 microm
      thick, and 1.5 cm long, and it has eight circular platinum-platinum chloride
      recording sites of 40-microm diameter distributed along the front and back
      surfaces with 1,500-microm intersite spacing. The system prototype was tested in
      six experiments where the electrode was implanted into the medial head of the
      gastrocnemius muscle of rabbits, perpendicular to the pennation angle of the
      muscle fibers. Asynchronous motor unit activity was induced by eliciting the
      withdrawal reflex or sequential crushes of the sciatic nerve using a pair of
      forceps. Sixty-seven motor units were identified from these recordings. In the
      bandwidth 200 Hz to 5 kHz, the peak-to-peak amplitude of the action potentials of
      the detected motor units was 75 +/- 12 muV and the root mean square of the noise
      was 1.6 +/- 0.4 muV. The noise level and amplitude of the action potentials were
      similar for measures separated by up to 40 min. The experimental tests
      demonstrated that thin film is a promising technology for a new type of flexible
      wire intramuscular EMG recording system with multiple detection sites.

PMID- 18048590
TI  - Effects of resistance exercise with and without creatine supplementation on gene
      expression and cell signaling in human skeletal muscle.
AB  - To test the hypothesis that creatine supplementation would enhance the anabolic
      responses of muscle cell signaling and gene expression to exercise, we studied
      nine subjects who received either creatine or a placebo (maltodextrin) for 5 days
      in a double-blind fashion before undergoing muscle biopsies: at rest, immediately
      after exercise (10 x 10 repetitions of one-leg extension at 80% 1 repetition
      maximum), and 24 and 72 h later (all in the morning after fasting overnight).
      Creatine supplementation decreased the phosphorylation state of protein kinase B
      (PKB) on Thr308 at rest by 60% (P < 0.05) and that of eukaryotic initiation
      factor 4E-binding protein on Thr37/46 (4E-BP1) by 30% 24 h postexercise (P <
      0.05). Creatine increased mRNA for collagen 1 (alpha(1)), glucose transporter-4
      (GLUT-4), and myosin heavy chain I at rest by 250%, 45%, and 80%, respectively,
      and myosin heavy chain IIA (MHCIIA) mRNA immediately after exercise by 70% (all P
      < 0.05). Immediately after exercise, and independent of creatine, mRNA for muscle
      atrophy F-box (MAFbx), MHCIIA, peroxisome proliferator-activated receptor gamma
      coactivator-1alpha, and interleukin-6 were upregulated (60-350%; P < 0.05); the
      phosphorylation state of p38 both in the sarcoplasm and nucleus were increased
      (12- and 25-fold, respectively; both P < 0.05). Concurrently, the phosphorylation
      states of PKB (Thr308) and 4E-BP1 (Thr37/46) were decreased by 50% and 75%,
      respectively (P < 0.05). Twenty-four hours postexercise, MAFbx, myostatin, and
      GLUT-4 mRNA expression decreased below preexercise values (-35 to -50%; P <
      0.05); calpain 1 mRNA increased 70% 72 h postexercise (P < 0.05) and at no other
      time. In conclusion, 5 days of creatine supplementation do not enhance anabolic
      signaling but increase the expression of certain targeted genes.

PMID- 18048592
TI  - Differential effects of acute hypoxia and high altitude on cerebral blood flow
      velocity and dynamic cerebral autoregulation: alterations with hyperoxia.
AB  - We hypothesized that 1) acute severe hypoxia, but not hyperoxia, at sea level
      would impair dynamic cerebral autoregulation (CA); 2) impairment in CA at high
      altitude (HA) would be partly restored with hyperoxia; and 3) hyperoxia at HA and
      would have more influence on blood pressure (BP) and less influence on middle
      cerebral artery blood flow velocity (MCAv). In healthy volunteers, BP and MCAv
      were measured continuously during normoxia and in acute hypoxia (inspired O2
      fraction = 0.12 and 0.10, respectively; n = 10) or hyperoxia (inspired O2
      fraction, 1.0; n = 12). Dynamic CA was assessed using transfer-function gain,
      phase, and coherence between mean BP and MCAv. Arterial blood gases were also
      obtained. In matched volunteers, the same variables were measured during air
      breathing and hyperoxia at low altitude (LA; 1,400 m) and after 1-2 days after
      arrival at HA ( approximately 5,400 m, n = 10). In acute hypoxia and hyperoxia,
      BP was unchanged whereas it was decreased during hyperoxia at HA (-11 +/- 4%; P <
      0.05 vs. LA). MCAv was unchanged during acute hypoxia and at HA; however, acute
      hyperoxia caused MCAv to fall to a greater extent than at HA (-12 +/- 3 vs. -5 +/
      4%, respectively; P < 0.05). Whereas CA was unchanged in hyperoxia, gain in the
      low-frequency range was reduced during acute hypoxia, indicating improvement in
      CA. In contrast, HA was associated with elevations in transfer-function gain in
      the very low- and low-frequency range, indicating CA impairment; hyperoxia
      lowered these elevations by approximately 50% (P < 0.05). Findings indicate that
      hyperoxia at HA can partially improve CA and lower BP, with little effect on
      MCAv.

PMID- 18048593
TI  - Apoptotic myocytes generate monocyte chemoattractant protein-1 and mediate
      macrophage recruitment.
AB  - The mechanisms by which apoptotic myocytes are removed by macrophages have not
      been fully elucidated. This study examined whether apoptotic myocytes actively
      recruit macrophages by generating monocyte chemoattractant protein-1 (MCP-1) in
      experiments in vitro and in vivo. Neonatal rat cardiac myocytes were incubated
      for 4 h in the presence or absence of staurosporine (STS, 0.2-1 mumol/l), an
      apoptosis inducer. Nuclear staining with DAPI showed that STS induced apoptosis
      in a dose-dependent fashion. STS (1 mumol/l) caused extensive DNA fragmentation
      and increased caspase-3 activity compared with a serum-deprived control. MCP-1
      mRNA and protein levels in myocytes increased twofold and fourfold, respectively,
      on STS treatment, and immunochemical staining revealed that apoptotic myocytes
      expressed MCP-1. To elucidate the role of MCP-1 expressed in apoptotic myocytes
      to recruit macrophages/monocytes, rat monocytes were incubated in the supernatant
      of STS-treated myocytes using a trans-well system. The culture medium of STS
      treated myocytes recruited monocytes in a MCP-1-dependent fashion. In addition,
      experiments were performed in vivo using ischemia-reperfused rat hearts. Rats
      were subjected to 30 min of ligation of the left coronary artery followed by 24 h
      of reperfusion. After the reperfusion, in the ischemic border myocardium, 17.1 +/
      1.1% of myocytes were terminal deoxynucleotidyl transferase-mediated dUTP nick
      end-labeling (TUNEL) positive. Moreover, double staining using the TUNEL
      technique and immunohistochemistry with MCP-1 antibody showed that 69.8 +/- 3.9%
      of TUNEL-positive myocytes expressed MCP-1 protein. Concomitantly, activated
      macrophages infiltrated the areas of apoptosis remarkably. These results suggest
      that apoptotic myocytes produce MCP-1, which have a critical role in the active
      recruitment of macrophages.

PMID- 18048594
TI  - Sound mind, sound body.

PMID- 18048595
TI  - Presidential address of the American Orthopaedic Society for Sports Medicine:
      coming full circle.

PMID- 18048597
TI  - "I always thought they were all pure tobacco": American smokers' perceptions of
      "natural" cigarettes and tobacco industry advertising strategies.
AB  - OBJECTIVE: To examine how the US tobacco industry markets cigarettes as "natural"
      and American smokers' views of the "naturalness" (or unnaturalness) of
      cigarettes. METHODS: Internal tobacco industry documents, the Pollay 20th Century
      Tobacco Ad Collection, and newspaper sources were reviewed, themes and strategies
      were categorised, and the findings were summarised. RESULTS: Cigarette
      advertisements have used the term "natural" since at least 1910, but it was not
      until the 1950s that "natural" referred to a core element of brand identity, used
      to describe specific product attributes (filter, menthol, tobacco leaf). The term
      "additive-free", introduced in the 1980s, is now commonly used to define natural
      cigarettes. Tobacco company market research, available from 1970 to 1998,
      consistently revealed that within focus group sessions, smokers initially had
      difficulty interpreting the term "natural" in relation to cigarettes; however,
      after discussion of cigarette ingredients, smokers viewed "natural" cigarettes as
      healthier. Tobacco companies regarded the implied health benefits of natural
      cigarettes as their key selling point, but hesitated to market them because doing
      so might raise doubts about the composition of their highly profitable "regular"
      brands. CONCLUSION: Although our findings support the idea advanced by some
      tobacco control advocates that informing smokers of conventional cigarettes'
      chemical ingredients could promote cessation, they also suggest that such a
      measure could increase the ubiquity and popularity of "natural" cigarettes. A
      more effective approach may be to "denaturalise" smoking.

PMID- 18048598
TI  - Smoking cessation attempts among adolescent smokers: a systematic review of
      prevalence studies.
AB  - OBJECTIVE: To synthesise estimates of the prevalence of cessation attempts among
      adolescent smokers generally, and according to age and level of cigarette
      consumption. DATA SOURCES: PubMed, ERIC, and PsychInfo databases and Internet
      searches of central data collection agencies. STUDY SELECTION: National
      population-based studies published in English between 1990 and 2005 reporting the
      prevalence, frequency and/or duration of cessation attempts among smokers aged
      >or=10 to <20 years. DATA EXTRACTION: Five reviewers determined inclusion
      criteria for full-text reports. One reviewer extracted data on the design,
      population characteristics and results from the reports. DATA SYNTHESIS: In
      total, 52 studies conformed to the inclusion criteria. The marked heterogeneity
      that characterised the study populations and survey questions precluded a meta
      analysis. Among adolescent current smokers, the median 6-month, 12-month and
      lifetime cessation attempt prevalence was 58% (range: 22-73%), 68% (range 43-92%)
      and 71% (range 28-84%), respectively. More than half had made multiple attempts.
      Among smokers who had attempted cessation, the median prevalence of relapse was
      34, 56, 89 and 92% within 1 week, 1 month, 6 months, and 1 year, respectively,
      following the longest attempt. Younger (age<16 years) and non-daily smokers
      experienced a similar or higher prevalence of cessation attempts compared with
      older (age >or=16 years) or daily smokers. Moreover, the prevalence of relapse by
      6 months following the longest cessation attempt was similar across age and
      smoking frequency. CONCLUSIONS: The high prevalence of cessation attempts and
      relapse among adolescent smokers extends to young adolescents and non-daily
      smokers. Cessation surveillance, research and program development should be more
      inclusive of these subgroups.

PMID- 18048599
TI  - Philip Morris's website and television commercials use new language to mislead
      the public into believing it has changed its stance on smoking and disease.
AB  - OBJECTIVES: This paper analyses Philip Morris's evolving website and the legal
      strategies employed in its creation and dissemination. METHODS: Internal tobacco
      documents were searched and examined and their substance verified and
      triangulated using media accounts, legal and public health research papers, and
      visits to Philip Morris's website. Various drafts of website language, as well as
      informal discussion of the website's creation, were located in internal Philip
      Morris documents. I compared website statements pertaining to Philip Morris's
      stance on cigarette smoking and disease with statements made in tobacco trials.
      RESULTS: Philip Morris created and disseminated its website's message that it
      agreed that smoking causes disease and is addictive in an effort to sway public
      opinion, while maintaining in a litigation setting its former position that it
      cannot be proved that smoking causes disease or is addictive. CONCLUSIONS: Philip
      Morris has not changed its position on smoking and health or addiction in the one
      arena where it has the most to lose-in the courtroom, under oath.

PMID- 18048600
TI  - Working to make a disease.

PMID- 18048611
TI  - Impact of smoking images in magazines on the smoking attitudes and intentions of
      youth: an experimental investigation.
AB  - OBJECTIVE: To determine the effect of magazine incidental smoking imagery on
      youths' smoking intentions. METHODS: A magazine was developed incorporating
      photographs of smokers (Smoking Magazine). A second version of the magazine (Non
      smoking Magazine) included these photographs with the tobacco paraphernalia
      digitally erased. Equal numbers of smokers and non-smokers aged 14-17 years (n =
      357) were randomly assigned to look through one version of the magazine and then
      asked a series of questions. RESULTS: Smokers made more unprompted mention of
      smoking imagery than non-smokers after viewing Smoking Magazine (52% vs 34%;
      p<0.05). Smokers viewing Smoking Magazine were more likely to report an urge to
      smoke (54% vs 40%; p<0.05). Female non-smokers who viewed Smoking Magazine were
      more likely than those who viewed Non-smoking Magazine to state a future
      intention to smoke (13% vs 0%; p<0.05). Female smokers were more attracted to the
      male models appearing in Smoking Magazine than Non-smoking Magazine (49% vs 24%;
      p<0.05) and the opposite was true for female non-smokers (28% vs 52%; p<0.05).
      Female smokers were also marginally more likely to desire looking like the female
      models in Smoking Magazine (64% vs 46%; p = 0.06) but no difference was observed
      in the non-smoking females (46% vs 46%). Male smokers and non-smokers did not
      differ in their responses by magazine type. CONCLUSIONS: Incidental positive
      smoking imagery in magazines can generate the same sorts of consumer effects
      attributed to advertising in general, including tobacco advertising. Sex specific
      results of our study may be explained by the choice of smoking images used.

PMID- 18048612
TI  - Mortality attributable to passive smoking in Spain, 2002.
AB  - OBJECTIVE: Exposure to environmental tobacco smoke (ETS) is associated with a
      variety of health effects, including lung cancer and ischaemic heart disease. The
      objective of this study was to estimate the number of deaths caused by exposure
      to ETS among non-smokers in Spain during the year 2002 METHODS: Prevalence of ETS
      exposure among never smokers was gathered from three region based health
      interview surveys. The relative risks of lung cancer and ischaemic heart diseases
      were selected from three meta-analyses. Population attributable risk (PAR) was
      computed using a range of prevalences (minimum-maximum). The number of deaths
      attributable to ETS was calculated by applying PARs to mortality not attributable
      to active smoking in 2002. The analyses were stratified by sex, age and source of
      exposure (home, workplace and both combined). In addition, a sensitivity analysis
      was performed for different scenarios. RESULTS: Among men, deaths attributable to
      ETS ranged from 408 to 1703. From 247 to 1434 of these deaths would be caused by
      the exposure only at home, 136-196 by exposure only in the workplace and 25-73 by
      exposure at both home and the workplace. Among women, the number of attributable
      deaths ranged from 820 to 1534. Between 807 and 1477 of these deaths would be
      caused by exposure only at home, 9-32 by exposure only in the workplace and 4-25
      by exposure both at home and in the workplace. CONCLUSION: Exposure to ETS at
      home and at work in Spain could be responsible for 1228-3237 of deaths from lung
      cancer and ischaemic heart disease. These data confirm that passive smoking is an
      important public health problem in Spain that needs urgent attention.

PMID- 18048614
TI  - Use of nicotine replacement therapy to reduce or delay smoking but not to quit:
      prevalence and association with subsequent cessation efforts.
AB  - OBJECTIVE: To assess the prevalence of nicotine replacement therapy (NRT) use for
      purposes other than quitting smoking and examine the relation of this non
      standard NRT use (NSNRT) with subsequent smoking cessation efforts. DESIGN: A
      population based cohort study of adult smokers who were interviewed by telephone
      at baseline (2001-2) and at two year follow-up. The association between NSNRT use
      to cut down on smoking or to delay smoking before baseline and cessation attempts
      and smoking outcomes at two year follow-up was assessed using logistic regression
      to adjust for multiple potential confounding factors. SETTING: Massachusetts,
      USA. SUBJECTS: 1712 adult smokers in Massachusetts who were selected using a
      random digit dial telephone survey. MAIN OUTCOME MEASURES: Quit attempt in 12
      months before follow-up, NRT use at quit attempt in 12 months before follow-up,
      smoking cessation by follow-up, or 50% reduction in cigarettes smoked per day
      between baseline and follow-up. RESULTS: 18.7% of respondents reported ever
      having used NSNRT. In a multiple logistic regression analysis, there was no
      statistically significant association between past NSNRT use and quit attempts
      (OR(cut down) = 0.89, 95% CI 0.59 to 1.33; OR(delay) = 1.29, 95% CI 0.73 to
      2.29), smoking cessation (OR(cut down) = 0.74, 95% CI 0.43 to 1.24; OR(delay) =
      1.22, 95% CI 0.60 to 2.50) or 50% reduction in cigarettes smoked per day (OR(cut
      down) = 0.93, 95% CI 0.62 to 1.38; OR(delay) = 0.80, 95% CI 0.43 to 1.49) at
      follow-up. Past use of NRT to cut down on cigarettes was associated with use of
      NRT at a follow-up quit attempt (OR(cut down) = 2.28, 95% CI 1.50 to 3.47) but
      past use of NRT to delay smoking was not (OR(delay) = 1.25, 95% CI 0.67 to 2.34).
      CONCLUSIONS: Use of NRT for reasons other than quitting smoking may be more
      common than was previously estimated. This population based survey finds no
      strong evidence that NRT use for purposes other than quitting smoking is either
      harmful or helpful.

PMID- 18048613
TI  - Exposure to domestic violence associated with adult smoking in India: a
      population based study.
AB  - OBJECTIVE: To investigate the relation between domestic violence and tobacco use
      among adults in India. DESIGN: Multilevel cross sectional analyses of a
      nationally representative population based sample from the 1998-9 Indian national
      family health survey. PARTICIPANTS: 278,977 individuals aged 15 or older; and
      89,092 ever married women aged 15-49. MAIN OUTCOME: Dichotomous variables for
      smoking and chewing tobacco. RESULTS: Women who reported being abused more than
      one year ago and those who reported being abused in the past year were more
      likely to smoke and chew tobacco than women who have never experienced domestic
      violence. Compared to individuals who lived in homes where no abuse was reported,
      those who lived in homes where a woman reported experiencing domestic violence
      were more likely to smoke and chew tobacco. CONCLUSION: Domestic violence is
      associated with higher odds of smoking and chewing tobacco in India. Efforts to
      control tobacco use need to consider the larger psychosocial circumstances within
      which individuals who practise such harmful health behaviours reside.

PMID- 18048615
TI  - Ultrafine particle emissions from waterpipes.
AB  - OBJECTIVES: Ultrafine particle emissions from waterpipes and their impact on
      human health have not been extensively studied. The aim of this study was to
      characterise the inhalation pattern of waterpipe smokers, and (a) construct
      apparatus to simulate waterpipe smoking in the laboratory, and (b) characterise
      mainstream emissions from waterpipes under different smoking conditions. METHODS:
      Real life waterpipe smoking patterns were first measured with a spirometer. The
      average smoking pattern was then mechanically simulated in apparatus. Total
      particle number concentrations were determined with a condensation particle
      counter (CPC) for particles between 0.02 microm and 1 microm (P-Trak UPC, Model
      8525, TSI) and the particle size fraction was determined with a differential
      mobility analyser (DMA) for particles from 0.01 microm to 0.5 microm. This
      instrument was coupled with a laser particle spectrometer for particles between
      0.35 microm and 10 microm (Wide Range Particle Spectrometer, Model 1000XP, MSC
      Corp). Carbon monoxide levels were determined with an electrochemical sensor (Q
      Trak monitor, Model 8554, TSI). RESULTS: The tidal volume of an average waterpipe
      breath of 5 seconds was found to be 1 (SD 0.47) litre. The intervals between
      breaths on average were 25.5 (SD 10.2) seconds. Particle number concentrations of
      ultrafine particles in mainstream smoke during waterpipe smoking ranged up to 70
      x 10(9) particles per litre. The median diameter of the particles in a full
      smoking set with charcoal, tobacco and water was 0.04 microm. Smoke from the
      heated tobacco contributed to particles in the size range between 0.01 microm and
      0.2 microm. The glowing piece of charcoal only contributed to particles smaller
      than 0.05 microm. CONCLUSIONS: Waterpipe smoking emits large amounts of ultrafine
      particles. With regard to particle emissions, smoking waterpipes may carry
      similar health risks to smoking cigarettes.

PMID- 18048616
TI  - Lifetime medical expenditure and life expectancy lost attributable to smoking
      through major smoking related diseases in Taiwan.
AB  - OBJECTIVE: To estimate the lifetime financial burden on Taiwan's national health
      insurance (NHI) system, life expectancy and years of life expectancy lost (YLEL)
      attributable to smoking from major smoking related diseases. METHODS: 10 major
      smoking related diseases (seven cancers, stroke, acute myocardial infarction and
      chronic obstructive pulmonary disease) were selected for this study. A survival
      analysis was conducted on linked cohorts from the National Death Registry
      database and the National Cancer Registry (NCR) and patients at the National
      Taiwan University Hospital (NTUH). Estimation of the smoking attributable
      fraction (SAF) for the study diseases was undertaken by combining the relative
      risks of smokers against non-smokers and the prevalence of smoking in Taiwan. The
      YLEL attributable to smoking was calculated for the study diseases by combining
      the survival analysis results, the SAF and the annual incidences of each disease.
      The lifetime medical expenditure for the study diseases was estimated by
      integrating the survival curve and the mean annual medical costs calculated from
      NHI reimbursement records. RESULTS: There were 241 280 incidents of the 10 study
      diseases in 2001, of which about 53 648 cases (22.2%) were attributable to
      smoking, with a total YLEL of 191 313 at an average of about 3.6 YLEL per case.
      For each case, the average survival time was about 10.2 years. Under two
      different annual discount rates, the total lifetime financial burden on the NHI
      was estimated at between $291 million ( pound 147 million; euro 216 million) (3%
      discount) and $336 million (1% discount) for all diseases attributable to smoking
      in 2001, accounting for about 24.6% of the total estimated lifetime medical
      expenditure for all incidents of the 10 study diseases. CONCLUSIONS: Smoking
      places tremendous financial and health burdens upon both society and individuals.
      A much more stringent tobacco control strategy is needed to curb the damage from
      smoking.

PMID- 18048617
TI  - Assessing the impact of smoking cessation services on reducing health
      inequalities in England: observational study.
AB  - OBJECTIVE: NHS stop smoking services are expected to play a key part in achieving
      the infant mortality and life expectancy health inequality targets in England by
      reducing smoking prevalence in deprived areas. This paper assesses the extent to
      which services have made a contribution to reducing inequalities in smoking
      between 2003-4 and 2005-6. METHODS: Synthetic estimates of baseline smoking
      prevalence data were compared with national monitoring data about the numbers of
      smokers in receipt of services and the proportion who self report quitting at
      four weeks. The social distribution of service recipients and quitters was
      compared with estimates of smoking prevalence to assess impact on inequalities.
      Comparisons were made between officially designated disadvantaged areas (the
      Spearhead Group) and others. RESULTS: Short-term cessation rates were lower in
      disadvantaged areas (52.6%) than elsewhere (57.9%) (p<0.001), but the proportion
      of smokers being treated was higher (16.7% compared with 13.4%) (p<0.001). The
      net effect was that a higher proportion of smokers in the most disadvantaged
      areas reported success (8.8%) than in more advantaged areas (7.8%) (p<0.001).
      Using the evidence-based assumption that three-quarters of short-term quitters
      will relapse within one year, the absolute and relative rate gaps in smoking
      prevalence between Spearhead areas and others are estimated to fall by small but
      statistically significant amounts from 5.2 and 1.215 (CIs: 1.216 to 1.213) to 5.0
      and 1.212 (CIs: 1.213 to 1.210) between 2003-4 and 2005-6. CONCLUSION: NHS stop
      smoking services have probably made a modest contribution to reducing
      inequalities in smoking prevalence. To achieve government targets, however,
      requires both the development of more innovative cessation interventions for the
      most addicted smokers and action to ensure that other aspects of tobacco control
      policy make a larger contribution to inequality goals.

PMID- 18048618
TI  - The costs of smoking in Vietnam: the case of inpatient care.
AB  - OBJECTIVE: To estimate the social costs of smoking related to inpatient care in
      Vietnam using 2005 data. DESIGN: The cost of illness as a result of
      hospitalisation for three major smoking-related diseases combined with the
      prevalence-based approach to obtain the costs of smoking in Vietnam for inpatient
      care. MAIN OUTCOME MEASURE: Smoking-attributable costs of inpatient care for lung
      cancer, chronic obstructive pulmonary disease (COPD), and ischaemic heart
      disease. RESULTS: The total cost of inpatient health care caused by smoking in
      Vietnam reached at least 1 161 829 million Vietnamese dollars ($VN) (or $US 77.5
      million) in 2005. This represents about 0.22% of Vietnam gross domestic product
      (GDP) and 4.3% of total healthcare expenditure. The majority of these expenses
      are related to COPD treatment ($VN 1,033541 million or $US 68.9 million per year)
      followed by lung cancer ($VN 78,143 million, or $US 5.2 million per year) and
      ischaemic disease ($VN 50,145 million, or $US 3.3 million per year). The
      government directly finances about 51% of these costs. The rest is financed
      either by households (34%) or by the insurance sector (15%). CONCLUSIONS: The
      social costs of smoking in Vietnam as the percentage of GDP is lower compared to
      estimates from high-income countries. The true costs would be substantially
      higher if all smoking-related diseases, outpatient care and mortality-related
      costs are included. More research is needed to augment the estimates presented in
      this paper.

PMID- 18048619
TI  - Nicotine replacement therapy, professional therapy, snuff use and tobacco
      smoking: a study of smoking cessation strategies in southern Sweden.
AB  - OBJECTIVES: The strategies used to support smoking cessation among quitters were
      investigated according to year of smoking cessation and sociodemographic
      characteristics. METHODS: The 2004 public health survey in Skane, Sweden, is a
      cross-sectional study. A total of 27,757 people aged 18-80 answered a postal
      questionnaire. The participation rate was 59%. Different strategies to support
      smoking cessation--that is, no therapy, nicotine replacement (NRT), professional
      therapy and snus (snuff) use, were investigated among quitters according to year
      of smoking cessation, and demographic and socioeconomic characteristics. RESULTS:
      14.9% of the men and 18.1% of the women were daily smokers. The prevalence of
      daily snus use was 19.5% among men but only 2.3% among women. Stratifying the
      data according to year of smoking cessation (1938-2004) revealed a significant
      increase in active smoking cessation strategies such as NRT, professional therapy
      and snus use. NRT was more common among women (23.6%) than men (14.8%) among
      smokers who quit in 2000-4, but snus use was more common among men (30.4% versus
      8.7%). No replacement or other therapy at all was significantly more common among
      women (63.6%) than men (52.1%). People aged 35-80 years used more nicotine
      replacement than people aged 18-34, while men aged 18-34 used snus to quit
      smoking significantly more than men aged 55-80. CONCLUSIONS: Snus is used
      commonly among men as a support for smoking cessation in Sweden. Women use
      pharmacological NRT to a greater extent, but this can probably not compensate for
      the much higher extent of snuff use as a cessation strategy among men.

PMID- 18048620
TI  - Disease burden of adult lung cancer and ischaemic heart disease from passive
      tobacco smoking in China.
AB  - OBJECTIVE: To address the health hazards tobacco smoking imposes upon non-smokers
      in China, this paper estimates the burden of diseases in adults from passive
      tobacco smoking for two major diseases--lung cancer and ischaemic heart disease
      (IHD). METHODS: The disease burden was estimated in terms of both premature
      mortality and disability adjusted life years (DALYs), a measure that accounts for
      both the age at death and the severity of the morbidity. RESULTS: Passive smoking
      caused more than 22,000 lung cancer deaths in 2002 according to these estimates.
      When the toll of disability is added to that of mortality, passive smoking was
      responsible for the loss of nearly 230,000 years of healthy life from lung
      cancer. Using the evidence from other countries that links IHD to passive
      smoking, we estimated that approximately 33,800 IHD deaths could be attributable
      to passive smoking in China in 2002. Passive smoking is also responsible for the
      loss of more than one quarter of a million years of healthy life from IHD.
      Although most of the disease burden caused by active smoking occurs among men,
      women bear nearly 80% of the total burden from passive smoking. The number of
      deaths among women caused by passive smoking is about two-thirds of that caused
      by smoking for the two diseases we examined. CONCLUSION: Even without considering
      the passive smoking risks for other diseases and among children that have been
      documented in other countries, passive smoking poses serious health hazards for
      non-smokers, especially for adult female non-smokers in China, adding more
      urgency to the need for measures to be taken immediately to protect the health of
      non-smokers and curb the nation's tobacco epidemic.

PMID- 18048621
TI  - Comprehensive smoke-free legislation in England: how advocacy won the day.
AB  - OBJECTIVE: To examine how a government committed to a voluntary approach was
      forced by an effective advocacy coalition to introduce comprehensive smoke-free
      legislation. METHODS: A diary was kept from the start of the campaign in 2003,
      backed up by journal and press articles, and information downloaded from the web.
      Regular public opinion polls were also carried out to supplement government
      surveys and polls conducted by the media. RESULTS: The 1997 Labour Government was
      committed to a voluntary approach to deal with the problem of secondhand smoke.
      By 2003, efforts to persuade government to introduce regulation of workplace
      secondhand smoke through a health and safety code of practice with exemptions for
      the hospitality trade, had failed. Despite a lack of support from the government,
      including the health minister, a new strategy by health advocates focusing on
      comprehensive workplace legislation was able to succeed. CONCLUSIONS: In a
      democracy it is crucial to develop public knowledge and belief in the extent of
      the risks of secondhand smoke. Gaining public and media support for the issue can
      ensure that government has to take action and that the legislation will be
      enforceable. The interests of the tobacco industry and the hospitality trade
      differ and this can be used to gain hospitality trade support for comprehensive
      national legislation in order to ensure a level playing field and protection from
      litigation.

PMID- 18048622
TI  - Investigating cigarette affordability in 60 cities using the cigarette price
      daily income ratio.
AB  - OBJECTIVE: To investigate cigarette affordability in 60 cities. METHODS:
      Affordability of cigarettes is defined as the ratio of the price of one pack of
      cigarettes to daily income (cigarette price-daily income ratio: CPDIR). Daily
      income data were calculated using the mean of the seven occupations with the
      lowest daily wage, as listed in the 2006 Union Bank of Switzerland survey;
      cigarette prices in 2006 were sourced from the Economist Intelligence Unit.
      RESULTS: Cigarette affordability in most of the surveyed cities remains high.
      There is a tendency for cities with high income economies to have a high level of
      cigarette affordability. Most of the cities in Western Europe and South and North
      America have high cigarette affordability, whereas 66.7% of their counterparts in
      Eastern Europe have medium cigarette affordability. In Asia, all cities with high
      cigarette affordability belong to the group of upper middle to high income
      economies, except for the Philippines. In Africa, Johannesburg and Nairobi have
      high and medium levels of cigarette affordability, respectively. CONCLUSION:
      Cigarette affordability for most of the sampled cities, especially those in high
      income economies, is high. There is room for increasing cigarette prices via tax
      increases. There is a risk that the increase in cigarette prices in newly
      emerging economies lags behind the high speed of economic growth being
      experiencing. Tax increases should be given high priority.

PMID- 18048623
TI  - Quitlines.

PMID- 18048624
TI  - Minimal dataset for quitlines: a best practice.
AB  - OBJECTIVES: This paper discusses the development of a minimal dataset (MDS) for
      tobacco cessation quitlines across North America. The goal was to create a
      standardised instrument and protocol that would allow for comparisons and pooling
      of data across quitlines for evaluation and research purposes. Principles of
      utilisation focused evaluation were followed to achieve consensus across diverse
      stakeholder groups in two countries. METHODS: The North American Quitline
      Consortium (NAQC) assembled a working group with representatives from quitline
      service providers, funders, evaluators and researchers from Canada and the United
      States. An extensive, iterative consultation process over two years led to
      consensus on the evaluation domains, indicators and specific items. Descriptive
      information on quitline service models, data collection protocols and
      methodological issues were addressed. RESULTS: The resulting minimal dataset
      (MDS) includes 15 items collected from eligible callers at intake and eight items
      collected from smokers participating in evaluation. Recommendations for selecting
      evaluation participants, length of follow-up and repeat callers were developed.
      Full MDS questions and technical documents are available on the NAQC website.
      CONCLUSION: Adoption and implementation of the MDS occurred in the majority of
      North American quitlines by the end of 2006. Key success factors included a focus
      on utility and feasibility, a commitment to meeting multiple and varied needs,
      sensitivity to situational factors and investment in working interactively with
      stakeholders. The creation and implementation of a MDS across two countries is an
      important "first" in tobacco control which will help speed the creation of
      practice based evidence and facilitate practice based research.

PMID- 18048625
TI  - Effectiveness and cost effectiveness of television, radio and print
      advertisements in promoting the New York smokers' quitline.
AB  - OBJECTIVES: This study assessed the relative effectiveness and cost effectiveness
      of television, radio and print advertisements to generate calls to the New York
      smokers' quitline. METHODS: Regression analysis was used to link total county
      level monthly quitline calls to television, radio and print advertising
      expenditures. Based on regression results, standardised measures of the relative
      effectiveness and cost effectiveness of expenditures were computed. RESULTS:
      There was a positive and statistically significant relation between call volume
      and expenditures for television (p<0.01) and radio (p<0.001) advertisements and a
      marginally significant effect for expenditures on newspaper advertisements
      (p<0.065). The largest effect was for television advertising. However, because of
      differences in advertising costs, for every $1000 increase in television, radio
      and newspaper expenditures, call volume increased by 0.1%, 5.7% and 2.8%,
      respectively. CONCLUSIONS: Television, radio and print media all effectively
      increased calls to the New York smokers' quitline. Although increases in
      expenditures for television were the most effective, their relatively high costs
      suggest they are not currently the most cost effective means to promote a
      quitline. This implies that a more efficient mix of media would place greater
      emphasis on radio than television. However, because the current study does not
      adequately assess the extent to which radio expenditures would sustain their
      effectiveness with substantial expenditure increases, it is not feasible to
      determine a more optimal mix of expenditures.

PMID- 18048626
TI  - The association between advertising and calls to a tobacco quitline.
AB  - OBJECTIVE: This study assessed the cost effectiveness of different types of
      television and radio advertisements and the time of day in which advertisements
      were placed in generating calls to the Oregon tobacco quitline. DESIGN: Cost
      effectiveness was measured by cost per call, calculated as the cost of
      advertising divided by the number of quitline calls generated by that
      advertising. Advertising was bought in one-week or two-week blocks and included
      27 daytime television buys, 22 evening television buys and 31 radio buys.
      RESULTS: Cost effectiveness varied widely by medium, time of day and
      advertisement used. Daytime television was seven times more cost effective than
      evening television and also more cost effective than radio. The most effective
      advertisements at generating quitline calls were real life testimonials by people
      who lost family members to tobacco and advertisements that deal practically with
      how to quit. CONCLUSIONS: Placement of television advertisements during the day
      versus the evening can increase an advertisement's effectiveness in generating
      calls to a quitline. Some advertising messages were more effective than others in
      generating calls to a quitline. Quitline providers can apply findings from
      previous research when planning media campaigns. In addition, call volume should
      be monitored in order to assess the cost effectiveness of different strategies to
      promote use of the quitline.

PMID- 18048627
TI  - A systematic review of interventions for smokers who contact quitlines.
AB  - OBJECTIVE: To evaluate the effect of different types of adjunctive support to
      stop smoking for individuals contacting telephone "quitlines," including call
      back counselling, different counselling techniques and provision of self help
      materials. DATA SOURCES: This review includes quitline studies identified as part
      of Cochrane reviews of telephone counselling and self help materials for smoking
      cessation. We updated the searches for this review. STUDY SELECTION: We included
      studies that were randomised or quasi-randomised controlled trials of any
      quitline or related service with follow-up of at least six months. DATA
      EXTRACTION: Data were extracted by one author and checked by a second. The
      cessation outcome was numbers quit at longest follow-up taking the strictest
      definition of abstinence available, and assuming participants lost to follow-up
      continued to smoke. DATA SYNTHESIS: We identified 14 relevant studies. Eight
      studies (18 500 participants) comparing multiple call-backs to a single contact
      increased quitting in the intervention group (Mantel-Haenszel fixed effect odds
      ratio 1.41, 95% confidence interval 1.27 to 1.57). Two unpublished studies
      without sufficient data to include in the meta-analysis also reported positive
      effects. Three call-back trials compared two schedules of multiple calls. Two
      found a significant dose-response effect and one did not detect a difference. We
      did not find consistent differences in comparisons between counselling approaches
      (two trials) or between different types of self help materials supplied following
      quitline contact (three trials). CONCLUSIONS: Multiple call-back counselling
      improves long term cessation for smokers who contact quitline services. Offering
      more calls may improve success rates. We failed to detect an effect of the type
      of counselling or the type of self help materials supplied as adjuncts to
      quitline counselling.

PMID- 18048628
TI  - Smokers' acceptance of "cold calls" offering quitline services.
AB  - OBJECTIVE: A random sample of smokers was offered a transfer to the New York
      State Smokers' Quitline in order to assess smokers' acceptance of "cold calls"
      offering quitline services. METHOD: A 30-minute survey to assess adult tobacco
      use was administered to 121 western New York smokers who were originally sampled
      for a random digit dialled survey in 2005, and then re-interviewed one year
      later, between April and July 2006. Smokers' interest in receiving immediate
      quitline assistance was assessed at the end of the survey, when the smokers could
      choose to be transferred to the New York State Smokers' Quitline in order to
      receive the quitline's cessation services. RESULTS: 41% of smokers accepted the
      offer for, and subsequently received, New York State Smokers' Quitline services.
      After controlling for factors related to cessation, women were more likely to
      respond to the offer. CONCLUSIONS: Although telephone quitline utilisation is
      low, these data suggest that the demand is high and "cold calls" may be a
      strategy to extend the use of quitline cessation services.

PMID- 18048629
TI  - Increasing reach of quitline services in a US state with comprehensive tobacco
      treatment.
AB  - OBJECTIVE: The population reach of tobacco quitlines is an important measure of
      treatment seeking and penetration of services. Maine offers an opportunity to
      examine temporal changes in quitline reach and referral sources in the context of
      a comprehensive tobacco treatment programme. The impact of a $1.00 cigarette tax
      increase is also examined. METHODS: This is a descriptive analysis of Maine
      Tobacco Helpline call volume September 2001 to December 2006. Annual reach was
      estimated using a cross sectional state surveillance survey. Weekly call volume
      was examined during 2005, a year of marked changes in tobacco taxes and quitline
      resources. Referral patterns were analysed yearly. RESULTS: Maine's Tobacco
      Helpline observed more than a threefold increase in population reach during a
      four year interval, from 1.9% to over 6% per year. Calls increased substantially
      in 2005, concurrent with added hours of operation and a rise in the cigarette
      tax. Over time, callers increasingly reported hearing about the quitline from
      health professionals, from 10% in 2001 to 38% in 2006. CONCLUSIONS: Tobacco
      treatment programmes offering free nicotine therapy and professional medical
      education can drive quitline utilisation over time. Call volume can also be
      affected by quitline operational and policy changes that promote the reduction of
      tobacco use.

PMID- 18048630
TI  - Expanding access to nicotine replacement therapy through Minnesota's QUITLINE
      partnership.
AB  - BACKGROUND: Partnerships can expand the reach and effectiveness of quitlines
      while conserving limited tobacco control dollars. OBJECTIVE: To describe how the
      addition of free nicotine replacement therapy (NRT) to the "QUITPLAN Helpline" in
      Minnesota influenced triage and transfer to health plan quitlines and how efforts
      taken to re-establish balance in the partnership expanded population based access
      to NRT. METHODS: NRT provision began in September 2002. Call volumes, transfer
      rates and ClearWay Minnesota dollars spent serving health plan members were
      examined from May 2001 through November 2005. The process by which health plan
      quitlines began providing NRT as a result of the addition of NRT to the QUITPLAN
      Helpline in September 2002 was explored through interviews with health plan
      representatives. RESULTS: Following the addition of NRT to the QUITPLAN Helpline,
      the percentage of health plan members transferred to their health plans decreased
      because callers were resisting transfer to their health plans for telephone
      counselling that did not include NRT. Transfer rates eventually returned to pre
      NRT levels following sequential implementation of scripting changes, transfer
      requirements and collection of health plan identification numbers. These changes
      reduced ClearWay Minnesota dollars spent on providing services to insured
      Minnesotans. Through the partnership, all Minnesotans currently have access to
      both telephone counselling and NRT either at no or low cost. CONCLUSIONS:
      Minnesota's partnership has effectively expanded access to NRT through quitlines.
      The increased use of partnerships for providing quitline services may be
      effective in broadening population access while conserving limited tobacco
      control dollars for those without cessation benefits.

PMID- 18048631
TI  - Offering free NRT through a tobacco quitline: impact on utilisation and quit
      rates.
AB  - OBJECTIVE: To assess the impact on quitline utilisation and cessation outcomes of
      adding free nicotine patches to the existing programme offerings. METHODS:
      Tobacco use status data from the Ohio tobacco quitline were collected from a
      subset of quitline callers 6 months after the initial intake call. To evaluate
      the impact of the nicotine replacement therapy (NRT) initiative, quit rates for
      two groups were compared: those who entered and exited the quitline programme
      before the availability of free NRT (n = 4657) and those who entered and exited
      the quitline programme after the availability of free NRT (n = 5715). RESULTS:
      Call volume increased from 2351 intakes calls per month or 78 calls per day
      before the availability of free NRT to 3606 intake calls per month or 188 intakes
      per day following the availability of free NRT (p<0.0001). 7-day point prevalence
      abstinence at 6 months among all quitline callers increased from 10.3% (95%
      confidence interval (CI) 9.7 to 10.9) before the availability of NRT to 14.9%
      (95% CI 14.3 to 15.5) after the availability of NRT. CONCLUSION: Offering free
      NRT through a state quitline is an effective means of increasing quitline
      utilisation and improving quit rates.

PMID- 18048632
TI  - Cost effectiveness of the Oregon quitline "free patch initiative".
AB  - OBJECTIVE: We estimated the cost effectiveness of the Oregon tobacco quitline's
      "free patch initiative" compared to the pre-initiative programme. METHODS: Using
      quitline utilisation and cost data from the state, intervention providers and
      patients, we estimated annual programme use and costs for media promotions and
      intervention services. We also estimated annual quitline registration calls and
      the number of quitters and life years saved for the pre-initiative and free patch
      initiative programmes. Service utilisation and 30-day abstinence at six months
      were obtained from 959 quitline callers. We compared the cost effectiveness of
      the free patch initiative (media and intervention costs) to the pre-initiative
      service offered to insured and uninsured callers. We conducted sensitivity
      analyses on key programme costs and outcomes by estimating a best case and worst
      case scenario for each intervention strategy. RESULTS: Compared to the pre
      intervention programme, the free patch initiative doubled registered calls,
      increased quitting fourfold and reduced total costs per quit by $2688. We
      estimated annual paid media costs were $215 per registered tobacco user for the
      pre-initiative programme and less than $4 per caller during the free patch
      initiative. Compared to the pre-initiative programme, incremental quitline
      promotion and intervention costs for the free patch initiative were $86 (range
      $22-$353) per life year saved. CONCLUSIONS: Compared to the pre-initiative
      programme, the free patch initiative was a highly cost effective strategy for
      increasing quitting in the population.

PMID- 18048634
TI  - Aboriginal users of Canadian quitlines: an exploratory analysis.
AB  - OBJECTIVES: To conduct an exploratory, comparative study of the utilisation and
      effectiveness of tobacco cessation quitlines among aboriginal and non-aboriginal
      Canadian smokers. SETTING: Population based quitlines that provide free cessation
      information, advice and counselling to Canadian smokers. SUBJECTS: First time
      quitline callers, age 18 years of age and over, who called the quitline between
      August 2001 and December 2005 and who completed the evaluation and provided data
      on their ethnic status (n = 7082). MAIN MEASURES: Demographic characteristics and
      tobacco behaviours of participants at intake and follow-up; reasons for calling;
      actions taken toward quitting, and 6-month follow-up quit rates. RESULTS: 7% of
      evaluation participants in the time period reported aboriginal origins.
      Aboriginal participants were younger than non-aboriginals but had similar smoking
      status and level of addiction at intake. Concern about future health and current
      health problems were the most common reasons aboriginal participants called. Six
      months after intake aboriginals and non-aboriginals had taken similar actions
      with 57% making a 24-hour quit attempt. Quit rates were higher for aboriginals
      than non-aboriginals, particularly for men. The 6-month prolonged abstinence rate
      for aboriginal men was 16.7% compared with 7.2% for aboriginal women and 9.4% and
      8.3% for non-aboriginal men and women, respectively. CONCLUSIONS: This
      exploratory analysis showed that even without targeted promotion, aboriginal
      smokers do call Canadian quitlines, primarily for health related reasons. We also
      showed that the quitlines are effective at helping them to quit. As a population
      focused intervention, quitlines can reach a large proportion of smokers in a cost
      efficient manner. In aboriginal communities where smoking rates exceed 50% and
      multiple health risks and chronic diseases already exist, eliminating non
      ceremonial tobacco use must be a priority. Our results, although exploratory,
      suggest quitlines can be an effective addition to aboriginal tobacco cessation
      strategies.

PMID- 18048633
TI  - The effectiveness and cost effectiveness of telephone counselling and the
      nicotine patch in a state tobacco quitline.
AB  - OBJECTIVES: State and national tobacco quitlines have expanded rapidly and offer
      a range of services. We examined the effectiveness and cost effectiveness of
      offering callers single session versus multisession counselling, with or without
      free nicotine patches. METHODS: This 3x2 randomised trial included 4614 Oregon
      tobacco quitline callers and compared brief (one 15-minute call), moderate (one
      30-minute call and a follow-up call) and intensive (five proactive calls)
      intervention protocols, with or without offers of free nicotine patches (nicotine
      replacement therapy, NRT). Blinded staff assessed tobacco use by phone at 12
      months. RESULTS: Abstinence odds ratios were significant for moderate (OR = 1.22,
      CI = 1.01 to 1.48) and intensive (OR = 1.29, CI = 1.07 to 1.56) intervention, and
      for NRT (OR = 1.58, CI = 1.35 to 1.85). Intent to treat quit rates were as
      follows: brief no NRT (12%); brief NRT (17%); moderate no NRT (14%); moderate NRT
      (20%); intensive no NRT (14%); and intensive NRT (21%). Relative to brief no NRT,
      the added costs for each additional quit was $2467 for brief NRT, $1912 for
      moderate no NRT, $2109 for moderate NRT, $2641 for intensive no NRT, and $2112
      for intensive NRT. CONCLUSION: Offering free NRT and multisession telephone
      support within a state tobacco quitline led to higher quit rates, and similar
      costs per incremental quit, than less intensive protocols.

PMID- 18048635
TI  - Is a statewide tobacco quitline an appropriate service for specific populations?
AB  - OBJECTIVE: To assess whether smoking quit rates and satisfaction with the
      Washington State tobacco quitline (QL) services varied by race/ethnicity,
      socioeconomic status, area of residence (that is, urban versus non-urban), or sex
      of Washington QL callers. METHODS: From October 2004 into October 2005, we
      conducted telephone surveys of Washington QL callers about three months after
      their initial call to the QL. Analyses compared 7-day quit rates and satisfaction
      measures by race/ethnicity, education level, area of residence and sex (using
      alpha = 0.05). RESULTS: We surveyed half (n = 1312) of the 2638 adult smokers we
      attempted to contact. The 7-day quit rate among survey participants at the 3
      month follow-up was 31% (CI: 27.1% to 34.2%), 92% (CI: 89.9% to 94.1%) were
      somewhat/very satisfied overall with the QL programme, 97% (CI: 95.5% to 98.2%)
      indicated that they would probably/for sure suggest the QL to others and 95% (CI:
      92.9% to 96.4%) were somewhat/very satisfied with the QL specialist. Quit rate
      did not vary significantly by race/ethnicity, education level, area of residence
      or sex. Satisfaction levels were high across subpopulations. Almost all
      participants (99%) agreed that they were always treated respectfully during
      interactions with QL staff. CONCLUSIONS: The Washington QL appeared effective and
      well received by callers from the specific populations studied. States choosing
      to promote their QL more aggressively should feel confident that a tobacco QL can
      be an effective and well received cessation service for smokers who call from a
      broad range of communities.

PMID- 18048636
TI  - Effects of frequency and duration in telephone counselling for smoking cessation.
AB  - OBJECTIVE: This study evaluates alternative protocols in telephone counselling
      for smoking cessation. DESIGN: The American Cancer Society enrolled 6322 clients
      in a randomised trial comparing three counselling formats of varying duration and
      frequency of contact, with or without booster sessions, and mailed self help
      booklets without telephone counselling. SETTING AND PARTICIPANTS: Participants
      were drawn from callers to the American Cancer Society's National Cancer
      Information Center seeking assistance with smoking cessation who provided
      informed consent and were adult daily smokers, ready to make a quit attempt
      within two weeks, and from states not served by an evidence based proactive
      telephone counselling programme. OUTCOMES: Six-month cessation rates (30-day
      point prevalence) were measured in telephone interviews. RESULTS: There was a
      significant counselling effect. The overall cessation rates that were yielded by
      a brief protocol including booster sessions were equivalent to those obtained
      with the American Cancer Society's standard protocol with boosters. CONCLUSIONS:
      Based on these findings, the abbreviated protocol with five sessions and two
      boosters is considered to be an option for improving cost efficiency in the
      delivery of this service.

PMID- 18048637
TI  - Do state characteristics matter? State level factors related to tobacco cessation
      quitlines.
AB  - BACKGROUND: Quitline services are an effective population-wide tobacco cessation
      strategy adopted widely in the United States as part of state comprehensive
      tobacco control efforts. Despite widespread evidence supporting quitlines'
      effectiveness, many states lack sufficient financial resources to adequately fund
      and promote this service. Efforts to augment state tobacco control efforts might
      be fostered by greater knowledge of state level factors associated with the
      funding and implementation of those efforts. METHODS: We analysed data from the
      2004 North American Quitline Consortium survey and from publicly available
      sources to identify state level factors related to quitline implementation and
      funding. Factors included in the analyses were state demographic characteristics,
      tobacco use variables, state tobacco control spending, and economic and political
      climate variables. Univariate and multivariate regression analyses were
      conducted. RESULTS: The best fitting multivariate model that significantly
      predicted the presence or absence of a state quitline included only cigarette
      excise tax rate (p = 0.020). In terms of funding levels, states with high rates
      of cigarette consumption (p = 0.047) and with higher per capita expenditures for
      tobacco control programmes (p = 0 .0.004) were most likely to spend more on per
      capita operations budget for quitlines. CONCLUSION: State level factors appear to
      play a part in whether states had established quitlines by mid-2004 and the
      amount of per capita quitline funding.

PMID- 18048638
TI  - Tobacco quitlines: looking back and looking ahead.
AB  - Telephone based tobacco cessation services, or quitlines, have become central
      components of many comprehensive tobacco control programmes. This paper provides
      an overview of their history, noting milestones in the growth of quitlines. Key
      factors in their worldwide adoption were solid evidence from clinical trials with
      large community samples and strong backing from public health officials.
      Quitlines are now available throughout most of North America, Europe, Australia
      and in many other locations around the world. The paper also offers several
      recommendations for future directions in quitline practice and research.
      Benchmarks should be established for key areas of quitline implementation, such
      as accessibility, quality and cost efficiency. Advances in pharmacotherapy,
      telephony and web based applications should be investigated for opportunities to
      expand service offerings. Research and development are needed to determine how
      best to serve a diverse clientele in the most cost effective manner. Funding
      should be expanded and diversified to enable quitlines to serve much larger
      numbers of users. Healthcare providers should be targeted for quitline promotion,
      to engage them in a broad effort to increase the number of patients receiving
      cessation messages from clinicians. The goal of quitline promotion should expand
      to include an increase in unaided quit attempts in the population. Early research
      findings were quickly adopted in quitline practice, and future research to answer
      questions that have arisen through the implementation of quitlines will probably
      also find quick adoption.

PMID- 18048639
TI  - Tobacco cessation quitlines in North America: a descriptive study.
AB  - BACKGROUND: Quitlines have become an integral part of tobacco control efforts in
      the United States and Canada. The demonstrated efficacy and the convenience of
      telephone based counselling have led to the fast adoption of quitlines, to the
      point of near universal access in North America. However, information on how
      these quitlines operate in actual practice is not often readily available.
      OBJECTIVES: This study describes quitline practice in North America and examines
      commonalities and differences across quitlines. It will serve as a source of
      reference for practitioners and researchers, with the aim of furthering service
      quality and promoting continued innovation. DESIGN: A self administered
      questionnaire survey of large, publicly funded quitlines in the United States and
      Canada. A total of 52 US quitlines and 10 Canadian quitlines participated.
      Descriptive statistics are provided regarding quitline operational structures,
      clinical services, quality assurance procedures, funding sources and utilisation
      rates. RESULTS: Clinical services for the 62 state/provincial quitlines are
      supplied by a total of 26 service providers. Nine providers operate multiple
      quitlines, creating greater consistency in operation than would otherwise be
      expected. Most quitlines offer services over extended hours (mean 96 hours/week)
      and have multiple language capabilities. Most (98%) use proactive multisession
      counselling-a key feature of protocols tested in previous experimental trials.
      Almost all quitlines have extensive training programmes (>60 hours) for
      counselling staff, and over 70% conduct regular evaluation of outcomes. About
      half of quitlines use the internet to provide cessation information. A little
      over a third of US quitlines distribute free cessation medications to eligible
      callers. The average utilisation rate of the US state quitlines in the 2004-5
      fiscal year was about 1.0% across states, with a strong correlation between the
      funding level of the quitlines and the smokers' utilisation of them (r = 0.74,
      p<0.001). CONCLUSIONS: Quitlines in North America display core commonalities:
      they have adopted the principles of multisession proactive counselling and they
      conduct regular outcome evaluation. Yet variations, tested and untested, exist.
      Standardised reporting procedures would be of benefit to the field. Shared
      discussion of the rationale behind variations can inform future decision making
      for all North American quitlines.

PMID- 18048640
TI  - Placenta defects and embryonic lethality resulting from disruption of mouse
      hydroxysteroid (17-beta) dehydrogenase 2 gene.
AB  - Hydroxysteroid (17-beta) dehydrogenase 2 (HSD17B2) is a member of aldo-keto
      reductase superfamily, known to catalyze the inactivation of 17beta
      hydroxysteroids to less active 17-keto forms and catalyze the conversion of
      20alpha-hydroxyprogesterone to progesterone in vitro. To examine the role of
      HSD17B2 in vivo, we generated mice deficient in Hsd17b2 [HSD17B2 knockout (KO)]
      by a targeted gene disruption in embryonic stem cells. From the homozygous mice
      carrying the disrupted Hsd17b2, 70% showed embryonic lethality appearing at the
      age of embryonic d 11.5 onward. The embryonic lethality was associated with
      reduced placental size measured at embryonic d 17.5. The HSD17B2KO mice placentas
      presented with structural abnormalities in all three major layers: the decidua,
      spongiotrophoblast, and labyrinth. Most notable was the disruption of the
      spongiotrophoblast and labyrinthine layers, together with liquid-filled cysts in
      the junctional region and the basal layer. Treatments with an antiestrogen or
      progesterone did not rescue the embryonic lethality or the placenta defect in the
      homozygous mice. In hybrid background used, 24% of HSD17B2KO mice survived
      through the fetal period but were born growth retarded and displayed a phenotype
      in the brain with enlargement of ventricles, abnormal laminar organization, and
      increased cellular density in the cortex. Furthermore, the HSD17B2KO mice had
      unilateral renal degeneration, the affected kidney frequently appearing as a
      fluid-filled sac. Our results provide evidence for a role for HSD17B2 enzyme in
      the cellular organization of the mouse placenta.

PMID- 18048641
TI  - Intracellular mechanisms regulating corticotropin-releasing hormone receptor
      2beta endocytosis and interaction with extracellularly regulated kinase 1/2 and
      p38 mitogen-activated protein kinase signaling cascades.
AB  - Many important physiological roles of the urocortin (UCN) family of peptides as
      well as CRH involve the type 2 CRH receptor (CRH-R2) and downstream activation of
      multiple pathways. To characterize molecular determinants of CRH-R2 functional
      activity, we used HEK293 cells overexpressing recombinant CRH-R2beta and
      investigated mechanisms involved in attenuation of CRH-R2 signaling activity and
      uncoupling from intracellular effectors. CRH-R2beta-mediated adenylyl cyclase
      activation was sensitive to homologous desensitization induced by pretreatment
      with either UCN-II or the weaker agonist CRH. CRH-R2beta activation induced
      transient beta-arrestin1 and beta-arrestin2, as well as clathrin, recruitment to
      the plasma membrane. Beta-arrestin2 appeared to be the main beta-arrestin subtype
      associated with the receptor. This was followed by CRH-R2beta endocytosis in a
      mechanism that exhibited distinct agonist-dependent temporal characteristics. CRH
      R2beta also induced transient activation of the ERK1/2 and p38MAPK signaling
      cascades that peaked at 5 min and returned to basal within 20-30 min. Unlike
      p38MAPK, activated ERK1/2 was localized both in the cytoplasm and nucleus.
      Experiments employing inhibitors of receptor endocytosis showed that CRH-R2beta
      MAPK interaction does not require beta-arrestin, clathrin, or receptor
      endocytosis. Site-directed mutagenesis studies on CRH-R2beta C terminus showed
      that the amino acid cassette TAAV at the end of the C terminus is important for
      CRH-R2beta signaling because loss of a potential phospho-acceptor site in mutant
      receptors containing deletion or Ala substitution of the cassette TAAV resulted
      in reduced ERK1/2 activation and accelerated receptor internalization. These
      findings provide new insights about the signaling mechanisms regulating CRH
      R2beta functional activity and determining its biological responses.

PMID- 18048642
TI  - Estradiol stimulates transcription of nuclear respiratory factor-1 and increases
      mitochondrial biogenesis.
AB  - Estrogen has direct and indirect effects on mitochondrial activity, but the
      mechanisms mediating these effects remain unclear. Others reported that long-term
      estradiol (E(2)) treatment increased nuclear respiratory factor-1 (NRF-1) protein
      in cerebral blood vessels of ovariectomized rats. NRF-1 is a transcription factor
      that regulates the expression of nuclear-encoded mitochondrial genes, e.g.
      mitochondrial transcription factor A (TFAM), that control transcription of the
      mitochondrial genome. Here we tested the hypothesis that E(2) increases NRF-1
      transcription resulting in a coordinate increase in the expression of nuclear-
      and mitochondrial- encoded genes and mitochondrial respiratory activity. We show
      that E(2) increased NRF-1 mRNA and protein in MCF-7 breast and H1793 lung
      adenocarcinoma cells in a time-dependent manner. E(2)-induced NRF-1 expression
      was inhibited by the estrogen receptor (ER) antagonist ICI 182,780 and
      actinomycin D but not by phosphoinositide-3 kinase and MAPK inhibitors,
      indicating a genomic mechanism of E(2) regulation of NRF-1 transcription. An
      estrogen response element (ERE) in the NRF-1 promoter bound ER alpha and ER beta
      in vitro, and E(2) induced ER alpha and ER beta recruitment to this ERE in
      chromatin immunoprecipitation assays in MCF-7 cells. The NRF-1 ERE activated
      reporter gene expression in transfected cells. Small interfering RNA to ER alpha
      and ER beta revealed that ER alpha mediates E(2)-induced NRF-1 transcription. The
      E(2)-induced increase in NRF-1 was followed by increased TFAM and the
      transcription of Tfam-regulated mitochondrial DNA-encoded COI and NDI genes and
      increased mitochondrial biogenesis. Knockdown of NRF-1 blocked E(2) stimulation
      of mitochondrial biogenesis and activity, indicating a mechanism by which
      estrogens regulate mitochondrial function by increasing NRF-1 expression.

PMID- 18048643
TI  - Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase
      inhibitor, is active in patients with imatinib-resistant or -intolerant
      accelerated-phase chronic myelogenous leukemia.
AB  - Patients with imatinib-resistant or -intolerant accelerated-phase chronic
      myelogenous leukemia (CML-AP) have very limited therapeutic options. Nilotinib is
      a highly selective BCR-ABL tyrosine kinase inhibitor. This phase 2 trial was
      designed to characterize the efficacy and safety of nilotinib (400 mg twice
      daily) in this patient population with hematologic response (HR) as primary
      efficacy endpoint. A total of 119 patients were enrolled and had a median
      duration of treatment of 202 days (range, 2-611 days). An HR was observed in 56
      patients (47%; 95% confidence interval [CI], 38%-56%). Major cytogenetic response
      (MCyR) was observed in 35 patients (29%; 95% CI, 21%-39%). The median duration of
      HR has not been reached. Overall survival rate among the 119 patients after 12
      months of follow-up was 79% (95% CI, 70%-87%). Nonhematologic adverse events were
      mostly mild to moderate. Severe peripheral edema and pleural effusions were not
      observed. The most common grade 3 or higher hematologic adverse events were
      thrombocytopenia (35%) and neutropenia (21%). Grade 3 or higher bilirubin and
      lipase elevations occurred in 9% and 18% of patients, respectively, resulting in
      treatment discontinuation in one patient. In conclusion, nilotinib is an
      effective and well-tolerated treatment in imatinib-resistant and -intolerant CML
      AP. This trial is registered at www.clinicaltrials.gov as NCT00384228.

PMID- 18048644
TI  - In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit
      is achieved from a matched sibling allogeneic transplantation in first complete
      remission, and an autologous transplantation is less effective than conventional
      consolidation/maintenance chemotherapy in all patients: final results of the
      International ALL Trial (MRC UKALL XII/ECOG E2993).
AB  - An international collaboration was set up to prospectively evaluate the role of
      allogeneic transplantation for adults with acute lymphoblastic leukemia (ALL) and
      compare autologous transplantation with standard chemotherapy. Patients received
      2 phases of induction and, if in remission, were assigned to allogeneic
      transplantation if they had a compatible sibling donor. Other patients were
      randomized to chemotherapy for 2.5 years versus an autologous transplantation. A
      donor versus no-donor analysis showed that Philadelphia chromosome-negative
      patients with a donor had a 5-year improved overall survival (OS), 53% versus 45%
      (P = .01), and the relapse rate was significantly lower (P < or = .001). The
      survival difference was significant in standard-risk patients, but not in high
      risk patients with a high nonrelapse mortality rate in the high-risk donor group.
      Patients randomized to chemotherapy had a higher 5-year OS (46%) than those
      randomized to autologous transplantation (37%; P = .03). Matched related
      allogeneic transplantations for ALL in first complete remission provide the most
      potent antileukemic therapy and considerable survival benefit for standard-risk
      patients. However, the transplantation-related mortality for high-risk older
      patients was unacceptably high and abrogated the reduction in relapse risk. There
      is no evidence that a single autologous transplantation can replace
      consolidation/maintenance in any risk group. This study is registered at
      http://clinicaltrials.gov as NCT00002514.

PMID- 18048645
TI  - Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in
      the thymus.
AB  - Notch signaling establishes boundaries in the thymus by inducing T-cell
      commitment and inhibiting a B-cell choice. Here, we show a significant 1.6-fold
      increased generation of B-cell precursors in thymuses from mice deficient for
      Notch target Hes5 compared with wild-type littermates. We further show that
      culture of bone marrow-derived progenitors with increasing densities of purified
      immobilized Notch ligand (Delta1(ext-IgG)) induced increased expression of Notch
      targets Hes1 and Hes5, and that although Hes5-deficient progenitors responded
      appropriately to high densities of ligand, they misread intermediate and low
      densities. Together, our results suggest that to ensure an appropriate outcome in
      the thymus in response to a lower threshold of induced Notch signaling, induction
      of the additional target Hes5 is required.

PMID- 18048646
TI  - The retinoblastoma tumor suppressor is a critical intrinsic regulator for
      hematopoietic stem and progenitor cells under stress.
AB  - The retinoblastoma tumor suppressor protein (RB) plays important roles in the
      control of the cell division cycle. It is estimated that RB is
      dysfunctional/inactivated in up to 40% of human leukemias. The consequences of
      loss of RB on hematopoietic stem and progenitor cell (HSPC) function in vivo are
      incompletely understood. Here, we report that mice genetically deficient in Rb in
      all hematopoietic cells (Vav-Cre Rb knockout [KO] animals) showed altered
      contribution of distinct hematopoietic cell lineages to peripheral blood, bone
      marrow, and spleen; significantly increased extramedullary hematopoiesis in the
      spleen; and a 2-fold increase in the frequency of hematopoietic progenitor cells
      in peripheral blood. Upon competitive transplantation, HSPCs from Vav-Cre Rb KO
      mice contributed with an at least 4- to 6-fold less efficiency to hematopoiesis
      compared with control cells. HSPCs deficient in Rb presented with impaired cell
      cycle exit upon stress-induced proliferation, which correlated with impaired
      function. In summary, Rb is critical for hematopoietic stem and progenitor cell
      function, localization, and differentiation.

PMID- 18048648
TI  - MOST: detecting cancer differential gene expression.
AB  - We propose a new statistics for the detection of differentially expressed genes
      when the genes are activated only in a subset of the samples. Statistics designed
      for this unconventional circumstance has proved to be valuable for most cancer
      studies, where oncogenes are activated for a small number of disease samples.
      Previous efforts made in this direction include cancer outlier profile analysis
      (Tomlins and others, 2005), outlier sum (Tibshirani and Hastie, 2007), and
      outlier robust t-statistics (Wu, 2007). We propose a new statistics called
      maximum ordered subset t-statistics (MOST) which seems to be natural when the
      number of activated samples is unknown. We compare MOST to other statistics and
      find that the proposed method often has more power then its competitors.

PMID- 18048647
TI  - ZAP-70 enhances IgM signaling independent of its kinase activity in chronic
      lymphocytic leukemia.
AB  - We transduced chronic lymphocytic leukemia (CLL) cells lacking ZAP-70 with
      vectors encoding ZAP-70 or various mutant forms of ZAP-70 and monitored the
      response of transduced CLL cells to treatment with F(ab)(2) anti-IgM (anti-mu).
      CLL cells made to express ZAP-70, a kinase-defective ZAP-70 (ZAP-70-KA(369)), or
      a ZAP-70 unable to bind c-Cbl (ZAP-YF(292)) experienced greater intracellular
      calcium flux and had greater increases in the levels of phosphorylated p72(Syk),
      B-cell linker protein (BLNK), and phospholipase C-gamma, and greater activation
      of the Ig accessory molecule CD79b in response to treatment with anti-mu than did
      mock-transfected CLL cells lacking ZAP-70. Transfection of CLL cells with vectors
      encoding truncated forms of ZAP-70 revealed that the SH2 domain, but not the SH1
      domain, was necessary to enhance intracellular calcium flux in response to
      treatment with anti-mu. We conclude that ZAP-70 most likely acts as an adapter
      protein that facilitates B-cell receptor (BCR) signaling in CLL cells independent
      of its tyrosine kinase activity or its ability to interact with c-Cbl.

PMID- 18048649
TI  - Responding to serious medical error in general practice--consequences for the GPs
      involved: analysis of 75 cases from Germany.
AB  - OBJECTIVES: GPs' recollections about their 'most serious errors in treatment' and
      about the consequences for themselves. Does it make a difference, who (else)
      contributed to the error, or to its discovery or disclosure? METHODS: Anonymous
      questionnaire study concerning the 'three most serious errors in your career as a
      GP'. The participating doctors were given an operational definition of 'serious
      error'. They applied a special recall technique, using patient-induced
      associations to bring to mind former 'serious errors'. The recall method and the
      semi-structured 25-item questionnaire used were developed and piloted by the
      authors. The items were analysed quantitatively and by qualitative content
      analysis. SETTING: General practices in the North Rhine region in Germany: 32 GPs
      anonymously reported about 75 'most serious errors'. RESULTS: In more than half
      of the cases analysed, other people contributed considerably to the GPs' serious
      errors. Most of the errors were discovered and disclosed to the patient by
      doctors: either by the GPs themselves, or by colleagues. A lot of GPs suffered
      loss of reputation and loss of patients. However, the number of patients staying
      with their GP clearly exceeded the number leaving their GP, depending on who else
      contributed to the error, who discovered it and who disclosed it to the patient.
      CONCLUSIONS: The majority of patients still trusted their GP after a serious
      error, especially if the GP was not the only one who contributed to the error and
      if the GP played an active role in the discovery and disclosure or the error.

PMID- 18048650
TI  - How representative of primary care are research active practices? Cross-sectional
      survey.
AB  - BACKGROUND: There has been a continued trend towards undertaking primary care
      based research but the characteristics and generalizability of practices that
      participate in such research are not well known. OBJECTIVE: To compare research
      active and non-active practices in terms of practice demographics, disease
      prevalence and quality scores from the Quality and Outcomes Framework. DESIGN:
      Cross-sectional survey using publicly available data. SETTING: A total of 973
      general practices from the West Midlands, UK. MAIN OUTCOME MEASURES: Practice
      population characteristics, research status, disease prevalence, clinical and non
      clinical quality scores. RESULTS: Of 973 practices, 298 (31%) were defined as
      research active. Research active practices had younger populations (% over 65:
      15.2% versus 16.2%, z = 3.95, P < 0.0001) compared to non-research active
      practices, were larger [median list size 6123 (interquartile range, IQR, 3642
      9691) versus 4059 (IQR 2675-7060) z = 6.96, P < 0.0001] and more likely to be in
      deprived areas [median Townsend quintile 5 (IQR 3-5) versus 4 (IQR 3-5), z =
      3.23, P = 0.001]. Disease prevalence was similar in both research active and non
      active practices but the former attained higher median quality scores for both
      clinical [research active 534/550 (IQR 508-546) versus non-research active
      525/550 (IQR 483-542) z = 4.00, P < 0.0001] and non-clinical [310/320 (IQR 283
      319) versus 296/320 (IQR 265-314), z = 5.76, P < 0.0001] areas. CONCLUSION:
      General practices which participate in research are larger and located in more
      deprived areas than non-research active practices but disease prevalence is
      similar and research practices attain only modestly higher quality points.
      Research in research active practices is likely to be generalizable to the wider
      primary care community.

PMID- 18048651
TI  - Million-degree plasma pervading the extended Orion Nebula.
AB  - Most stars form as members of large associations within dense, very cold (10 to
      100 kelvin) molecular clouds. The nearby giant molecular cloud in Orion hosts
      several thousand stars of ages less than a few million years, many of which are
      located in or around the famous Orion Nebula, a prominent gas structure
      illuminated and ionized by a small group of massive stars (the Trapezium). We
      present x-ray observations obtained with the X-ray Multi-Mirror satellite XMM
      Newton, revealing that a hot plasma with a temperature of 1.7 to 2.1 million
      kelvin pervades the southwest extension of the nebula. The plasma flows into the
      adjacent interstellar medium. This x-ray outflow phenomenon must be widespread
      throughout our Galaxy.

PMID- 18048652
TI  - Switching from repression to activation: microRNAs can up-regulate translation.
AB  - AU-rich elements (AREs) and microRNA target sites are conserved sequences in
      messenger RNA (mRNA) 3' untranslated regions (3'UTRs) that control gene
      expression posttranscriptionally. Upon cell cycle arrest, the ARE in tumor
      necrosis factor-alpha (TNFalpha) mRNA is transformed into a translation
      activation signal, recruiting Argonaute (AGO) and fragile X mental retardation
      related protein 1 (FXR1), factors associated with micro-ribonucleoproteins
      (microRNPs). We show that human microRNA miR369-3 directs association of these
      proteins with the AREs to activate translation. Furthermore, we document that two
      well-studied microRNAs-Let-7 and the synthetic microRNA miRcxcr4-likewise induce
      translation up-regulation of target mRNAs on cell cycle arrest, yet they repress
      translation in proliferating cells. Thus, activation is a common function of
      microRNPs on cell cycle arrest. We propose that translation regulation by
      microRNPs oscillates between repression and activation during the cell cycle.

PMID- 18048653
TI  - Stellar feedback in dwarf galaxy formation.
AB  - Dwarf galaxies pose substantial challenges for cosmological models. In
      particular, current models predict a dark-matter density that is divergent at the
      center, which is in sharp contrast with observations that indicate a core of
      roughly constant density. Energy feedback, from supernova explosions and stellar
      winds, has been proposed as a major factor shaping the evolution of dwarf
      galaxies. We present detailed cosmological simulations with sufficient resolution
      both to model the relevant physical processes and to directly assess the impact
      of stellar feedback on observable properties of dwarf galaxies. We show that
      feedback drives large-scale, bulk motions of the interstellar gas, resulting in
      substantial gravitational potential fluctuations and a consequent reduction in
      the central matter density, bringing the theoretical predictions in agreement
      with observations.

PMID- 18048654
TI  - Climate change, deforestation, and the fate of the Amazon.
AB  - The forest biome of Amazonia is one of Earth's greatest biological treasures and
      a major component of the Earth system. This century, it faces the dual threats of
      deforestation and stress from climate change. Here, we summarize some of the
      latest findings and thinking on these threats, explore the consequences for the
      forest ecosystem and its human residents, and outline options for the future of
      Amazonia. We also discuss the implications of new proposals to finance
      preservation of Amazonian forests.

PMID- 18048655
TI  - The quality of public dialogue.

PMID- 18048656
TI  - Epidemiology. New estimates scale back scope of HIV/AIDS epidemic.

PMID- 18048657
TI  - Influenza. Tense meeting produces some hope for flu-sharing deal.

PMID- 18048658
TI  - Paleoanthropology. Hominid harems: big males competed for small australopithecine
      females.

PMID- 18048659
TI  - Museums. Smithsonian struggles to strike a balance with sponsors.

PMID- 18048660
TI  - Public science. Pilot NSF program flies into stiff community headwinds.

PMID- 18048661
TI  - Science advice. Germany finally picks a national science academy.

PMID- 18048662
TI  - Carbon sequestration. Should oceanographers pump iron?

PMID- 18048663
TI  - Higher education. MIT engineer shakes Korean academia to its core.

PMID- 18048664
TI  - Veterinary medicine. Camel scientists ask: what's sinking the ships of the
      desert?

PMID- 18048665
TI  - Veterinary medicine. 'Camelized' antibodies make waves.

PMID- 18048666
TI  - Space. Columbus injects science into station.

PMID- 18048667
TI  - Global and local conservation priorities.

PMID- 18048668
TI  - Comment on "Decagonal and quasi-crystalline tilings in medieval Islamic
      architecture".
AB  - Lu and Steinhardt (Reports, 23 February 2007, p. 1106) claimed the discovery of a
      large, potentially quasi-crystalline Islamic tiling in the Darb-i Imam shrine but
      regard the earlier Maragha tiling, previously described as quasiperiodic, as a
      small isolated motif. We demonstrate that the Darb-i Imam pattern is periodic and
      that the quasi-crystalline discs superimposed on its lattice are derivatives of
      the Maragha pattern.

PMID- 18048669
TI  - Climate change. Climate assessment: what's next?

PMID- 18048671
TI  - Geochemistry. The leaking mantle.

PMID- 18048670
TI  - Preschool program improves cognitive control.

PMID- 18048672
TI  - Genetics. Paradigm for life.

PMID- 18048673
TI  - Chemistry. Surface-conducting diamond.

PMID- 18048674
TI  - Chemistry. Metal-based therapeutics.

PMID- 18048675
TI  - Physics. Precision without entanglement.

PMID- 18048676
TI  - Genetics. Beta-defensin repertoire expands.

PMID- 18048677
TI  - Journey to the center of the cell. Introduction to special issue.

PMID- 18048678
TI  - Return of the matrix.

PMID- 18048679
TI  - Toward a high-resolution view of nuclear dynamics.
AB  - The nucleus is the defining feature of eukaryotic cells. It is a highly dynamic,
      membrane-bound organelle that encloses chromatin and thereby partitions gene
      transcription from sites of protein translation in the cytoplasm. Major cellular
      events, including DNA replication, messenger RNA synthesis and processing, and
      ribosome subunit biogenesis, take place within the nucleus, resulting in a
      continuous flux of macromolecules into and out of the nucleus through dedicated
      nuclear pore complexes in the nuclear envelope. Here, we review the impact of new
      technologies, especially in areas of fluorescence microscopy and proteomics,
      which are providing major insights into dynamic processes affecting both
      structure and function within the nucleus.

PMID- 18048680
TI  - Blurring the boundary: the nuclear envelope extends its reach.
AB  - The past decade has seen a complete rethinking of the traditional view of the
      nuclear envelope as simply a passive enclosure for the chromosomes. The
      convergence of several lines of clinical and basic research has revealed
      additional roles in both signaling and mitotic progression. It is becoming
      apparent that the nuclear envelope defines not only nuclear organization but also
      that of the cytoskeleton and, in this way, integrates both nuclear and
      cytoplasmic architecture.

PMID- 18048681
TI  - Crossing the nuclear envelope: hierarchical regulation of nucleocytoplasmic
      transport.
AB  - Transport of macromolecules between the nucleus and cytoplasm is a critical
      cellular process for eukaryotes, and the machinery that mediates
      nucleocytoplasmic exchange is subject to multiple levels of control. Regulation
      is achieved by modulating the expression or function of single cargoes, transport
      receptors, or the transport channel. Each of these mechanisms has increasingly
      broad impacts on transport patterns and capacity, and this hierarchy of control
      directly affects gene expression, signal transduction, development, and disease.

PMID- 18048682
TI  - Plants tolerant of high boron levels.
AB  - Reduced crop productivity due to soils containing toxic levels of boron (B) is a
      worldwide problem in food production. It is estimated that up to 17% of the
      barley yield losses in southern Australia are caused by B toxicity. We found that
      the expression of AtBOR4, an Arabidopsis paralog of BOR1, the first identified
      boron transporter gene, generates plants that are tolerant of high B levels. BOR4
      is a polarly localized borate exporter that enhances B efflux from roots. The
      present study is a foundation for the improvement of crop productivity in soils
      containing excess B, which are distributed in arid areas of the world.

PMID- 18048683
TI  - Charge transfer equilibria between diamond and an aqueous oxygen electrochemical
      redox couple.
AB  - Undoped, high-quality diamond is, under almost all circumstances, one of the best
      insulators known. However, diamond covered with chemically bound hydrogen shows a
      pronounced conductivity when exposed to air. This conductivity arises from
      positive-charge carriers (holes) and is confined to a narrow near-surface region.
      Although several explanations have been proposed, none has received wide
      acceptance, and the mechanism remains controversial. Here, we report the
      interactions of hydrogen-terminated, macroscopic diamonds and diamond powders
      with aqueous solutions of controlled pH and oxygen concentration. We show that
      electrons transfer between the diamond and an electrochemical reduction/oxidation
      couple involving oxygen. This charge transfer is responsible for the surface
      conductivity and also influences contact angles and zeta potentials. The effect
      is not confined to diamond and may play a previously unrecognized role in other
      disparate systems.

PMID- 18048684
TI  - Flow of mantle fluids through the ductile lower crust: helium isotope trends.
AB  - Heat and mass are injected into the shallow crust when mantle fluids are able to
      flow through the ductile lower crust. Minimum 3He/4He ratios in surface fluids
      from the northern Basin and Range Province, western North America, increase
      systematically from low crustal values in the east to high mantle values in the
      west, a regional trend that correlates with the rates of active crustal
      deformation. The highest ratios occur where the extension and shear strain rates
      are greatest. The correspondence of helium isotope ratios and active
      transtensional deformation indicates a deformation-enhanced permeability and that
      mantle fluids can penetrate the ductile lithosphere, even in regions where there
      is no substantial magmatism. Superimposed on the regional trend are local, high
      3He/4He anomalies indicating hidden magmatic activity and/or deep fluid
      production with locally enhanced permeability, identifying zones with high
      resource potential, particularly for geothermal energy development.

PMID- 18048685
TI  - In situ determination of the nanoscale chemistry and behavior of solid-liquid
      systems.
AB  - Many fundamental questions in crystal-growth behavior remain unanswered because
      of the difficulties encountered in simultaneously observing phases and
      determining elemental concentrations and redistributions while crystals nucleate
      and grow at the nanoscale. We show that these obstacles can be overcome by
      performing energy-dispersive x-ray spectroscopy on partially molten Al-Si-Cu-Mg
      alloy particles during in situ heating in a transmission electron microscope.
      Using this technique, we were able to (i) determine that the aluminum and silicon
      concentrations change in a complementary and symmetric manner about the solid
      liquid interface as a function of temperature; (ii) directly measure the solid-
      and liquid-phase compositions at equilibrium and in highly undercooled conditions
      for quantitative comparison with thermodynamic calculations of the liquidus and
      solidus phase boundaries; and (iii) provide direct evidence for homogeneous
      nucleation of the aluminum-rich solid.

PMID- 18048686
TI  - Fluctuation superconductivity in mesoscopic aluminum rings.
AB  - Fluctuations are important near phase transitions, where they can be difficult to
      describe quantitatively. Superconductivity in mesoscopic rings is particularly
      intriguing because the critical temperature is an oscillatory function of
      magnetic field. There is an exact theory for thermal fluctuations in one
      dimensional superconducting rings, which are therefore expected to be an
      excellent model system. We measured the susceptibility of many rings, one ring at
      a time, by using a scanning superconducting quantum interference device that can
      isolate magnetic signals that are seven orders of magnitude smaller than applied
      flux. We find that the fluctuation theory describes the results and that a single
      parameter characterizes the ways in which the fluctuations are especially
      important at magnetic fields where the critical temperature is suppressed.

PMID- 18048687
TI  - Extended male growth in a fossil hominin species.
AB  - In primates that are highly sexually dimorphic, males often reach maturity later
      than females, and young adult males do not show the size, morphology, and
      coloration of mature males. Here we describe extended male development in a
      hominin species, Paranthropus robustus. Ranking a large sample of facial remains
      on the basis of dental wear stages reveals a difference in size and robusticity
      between young adult and old adult males. Combined with estimates of sexual
      dimorphism, this pattern suggests that male reproductive strategy focused on
      monopolizing groups of females, in a manner similar to that of silverback
      gorillas. However, males appear to have borne a substantial cost in the form of
      high rates of predation.

PMID- 18048688
TI  - Boron-toxicity tolerance in barley arising from efflux transporter amplification.
AB  - Both limiting and toxic soil concentrations of the essential micronutrient boron
      represent major limitations to crop production worldwide. We identified Bot1, a
      BOR1 ortholog, as the gene responsible for the superior boron-toxicity tolerance
      of the Algerian barley landrace Sahara 3771 (Sahara). Bot1 was located at the
      tolerance locus by high-resolution mapping. Compared to intolerant genotypes,
      Sahara contains about four times as many Bot1 gene copies, produces substantially
      more Bot1 transcript, and encodes a Bot1 protein with a higher capacity to
      provide tolerance in yeast. Bot1 transcript levels identified in barley tissues
      are consistent with a role in limiting the net entry of boron into the root and
      in the disposal of boron from leaves via hydathode guttation.

PMID- 18048689
TI  - 5'-triphosphate-dependent activation of PKR by RNAs with short stem-loops.
AB  - Molecular patterns in pathogenic RNAs can be recognized by the innate immune
      system, and a component of this response is the interferon-induced enzyme RNA
      activated protein kinase (PKR). The major activators of PKR have been proposed to
      be long double-stranded RNAs. We report that RNAs with very limited secondary
      structures activate PKR in a 5'-triphosphate-dependent fashion in vitro and in
      vivo. Activation of PKR by 5'-triphosphate RNA is independent of RIG-I and is
      enhanced by treatment with type 1 interferon (IFN-alpha). Surveillance of
      molecular features at the 5' end of transcripts by PKR presents a means of
      allowing pathogenic RNA to be distinguished from self-RNA. The evidence presented
      here suggests that this form of RNA-based discrimination may be a critical step
      in mounting an early immune response.

PMID- 18048690
TI  - Direct observation of chaperone-induced changes in a protein folding pathway.
AB  - How chaperone interactions affect protein folding pathways is a central problem
      in biology. With the use of optical tweezers and all-atom molecular dynamics
      simulations, we studied the effect of chaperone SecB on the folding and unfolding
      pathways of maltose binding protein (MBP) at the single-molecule level. In the
      absence of SecB, we find that the MBP polypeptide first collapses into a molten
      globulelike compacted state and then folds into a stable core structure onto
      which several alpha helices are finally wrapped. Interactions with SecB
      completely prevent stable tertiary contacts in the core structure but have no
      detectable effect on the folding of the external alpha helices. It appears that
      SecB only binds to the extended or molten globulelike structure and retains MBP
      in this latter state. Thus during MBP translocation, no energy is required to
      disrupt stable tertiary interactions.

PMID- 18048691
TI  - Carbon dioxide activation at the Ni,Fe-cluster of anaerobic carbon monoxide
      dehydrogenase.
AB  - Anaerobic CO dehydrogenases catalyze the reversible oxidation of CO to CO2 at a
      complex Ni-, Fe-, and S-containing metal center called cluster C. We report
      crystal structures of CO dehydrogenase II from Carboxydothermus hydrogenoformans
      in three different states. In a reduced state, exogenous CO2 supplied in solution
      is bound and reductively activated by cluster C. In the intermediate structure,
      CO2 acts as a bridging ligand between Ni and the asymmetrically coordinated Fe,
      where it completes the square-planar coordination of the Ni ion. It replaces a
      water/hydroxo ligand bound to the Fe ion in the other two states. The structures
      define the mechanism of CO oxidation and CO2 reduction at the Ni-Fe site of
      cluster C.

PMID- 18048692
TI  - Solvent tuning of electrochemical potentials in the active sites of HiPIP versus
      ferredoxin.
AB  - A persistent puzzle in the field of biological electron transfer is the conserved
      iron-sulfur cluster motif in both high potential iron-sulfur protein (HiPIP) and
      ferredoxin (Fd) active sites. Despite this structural similarity, HiPIPs react
      oxidatively at physiological potentials, whereas Fds are reduced. Sulfur K-edge x
      ray absorption spectroscopy uncovers the substantial influence of hydration on
      this variation in reactivity. Fe-S covalency is much lower in natively hydrated
      Fd active sites than in HiPIPs but increases upon water removal; similarly, HiPIP
      covalency decreases when unfolding exposes an otherwise hydrophobically shielded
      active site to water. Studies on model compounds and accompanying density
      functional theory calculations support a correlation of Fe-S covalency with ease
      of oxidation and therefore suggest that hydration accounts for most of the
      difference between Fd and HiPIP reduction potentials.

PMID- 18048694
TI  - Inhibition of the cardiac L-type calcium channel current by antidepressant drugs.
AB  - Antidepressants inhibit many membrane receptors and ionic channels, including the
      L-type calcium channel. Here, we investigated the inhibition of calcium current
      (I(Ca)) by antidepressants in enzymatically isolated rat ventricular myocytes
      using whole-cell patch clamp. The molecular mechanism of inhibition was studied
      by comparing the voltage and state dependence of antidepressant inhibition of
      I(Ca) to the respective properties of calcium antagonists, and by studying the
      effect of (+/-)-1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-[trifluoromethyl]phenyl)-3
      pyridine carboxylic acid methyl ester (Bay K8644) or diltiazem on the inhibitory
      potency of the antidepressants. All selected antidepressants inhibited calcium
      currents reversibly and concentration-dependently. At a stimulation frequency of
      0.33 Hz, the antidepressants imipramine, clomipramine, desipramine,
      amitriptyline, maprotiline, citalopram, and dibenzepin blocked I(Ca), with IC(50)
      values of 8.3, 11.6, 11.7, 23.2, 31.0, 64.5, and 364 muM. The antidepressant
      drugs shifted steady-state inactivation curves of I(Ca) to negative voltages. The
      extent of the shift was similar to that induced by diltiazem or verapamil, but it
      was significantly smaller than that induced by felodipine. The use-dependent
      component of the antidepressant-induced block was similar to that of diltiazem,
      and it was significantly more and less, respectively, than those of felodipine
      and verapamil. In the presence of Bay K8644, antidepressants were more effective
      in inhibiting I(Ca). However, the inhibitory effect of antidepressants was also
      augmented by diltiazem, suggesting that these drugs do not compete with diltiazem
      for a single binding site. These data suggest that antidepressants exert their
      inhibitory action on cardiac L-type calcium channels by a specific interaction at
      a receptor site similar to, but distinct from, the benzothiazepine site.

PMID- 18048693
TI  - Expression and function of junctional adhesion molecule-C in myelinated
      peripheral nerves.
AB  - JAM-C is an adhesion molecule that is expressed on cells within the vascular
      compartment and epithelial cells and, to date, has been largely studied in the
      context of inflammatory events. Using immunolabeling procedures in conjunction
      with confocal and electron microscopy, we show here that JAM-C is also expressed
      in peripheral nerves and that this expression is localized to Schwann cells at
      junctions between adjoining myelin end loops. Sciatic nerves from JAM-C-deficient
      [having the JAM-C gene knocked out (KO)] mice exhibited loss of integrity of the
      myelin sheath and defective nerve conduction as indicated by morphological and
      electrophysiological studies, respectively. In addition, behavioral tests showed
      motor abnormalities in the KO animals. JAM-C was also expressed in human sural
      nerves with an expression profile similar to that seen in mice. These results
      demonstrate that JAM-C is a component of the autotypic junctional attachments of
      Schwann cells and plays an important role in maintaining the integrity and
      function of myelinated peripheral nerves.

PMID- 18048696
TI  - Doctors and the drug industry revisited.

PMID- 18048695
TI  - Involvement of P2Y1 and P2Y11 purinoceptors in parasympathetic inhibition of
      colonic smooth muscle.
AB  - Purinergic signaling was first recognized in the guinea pig (Cavia porcellus)
      taenia coli, where relaxation of smooth muscle by nerve-released ATP may involve
      the activation of P2Y(1) and P2Y(11) receptors, and where transcripts for both
      genes have been found. A partial sequence for P2Y(11) protein was identified; the
      full-length P2Y(1) sequence has already been described. P2Y(1) and P2Y(11)
      proteins were localized by immunohistochemistry in smooth muscle cells. P2X(2)
      and P2X(3) proteins were also localized in motoneurons of the myenteric plexus.
      alphabeta-Methylene-ATP (alphabetameATP) and dibenzoyl-ATP (BzATP) evoked fast
      relaxations in the taenia, and they were inhibited by the P2Y(1) receptor
      antagonist 2'-deoxy-N(6)-methyladenosine 3',5'-bisphosphate (MRS2179). However,
      alphabetameATP and BzATP may stimulate neuronal P2X receptors to release ATP,
      which then acts on P2Y(1) receptors. In accordance, fast relaxations evoked by
      alphabetameATP and BzATP were inhibited by the P2X(3) and P2X(2/3) receptor
      antagonist 5-({[3-phenoxybenzyl][(1S)-1,2,3,4-tetrahydro-1-naphthalenyl] amino}
      carbonyl)-1,2,4-benzene-tricarboxylic acid (A317491). When P2Y(1), P2X(3), and
      P2X(2/3) receptors were blocked and adenosine was removed enzymatically,
      alphabetameATP and BzATP evoked slow relaxations that were inhibited by Reactive
      Red. Fast and slow relaxations involve small and large conductance calcium
      activated potassium channels; the latter are dependent on intracellular cyclic
      AMP levels, which altered the duration and amplitude of relaxations.
      alphabetameATP and BzATP were confirmed as agonists, and Reactive Red as an
      antagonist, of human P2Y(11) receptors. In summary, G(q)-coupled P2Y(1) receptors
      are involved mainly in fast relaxations, whereas G(q)and G(s)-coupled P2Y(11)
      receptors are involved in both fast and slow relaxations. These P2Y receptor
      subtypes, plus neuronal P2X receptors, may explain the phenomenon of
      parasympathetic inhibition first described by Langley (1898).

PMID- 18048697
TI  - British medicine's desperate need for leadership.

PMID- 18048698
TI  - Emergency admissions a time for action and improving patient outcomes.

PMID- 18048699
TI  - The nose and sex: the nasogenital reflex revisited.

PMID- 18048700
TI  - Count me in even if I am old!

PMID- 18048702
TI  - Chronic diarrhoea.

PMID- 18048703
TI  - Heroin injecting and the introduction of HIV/AIDS into a Scottish city.

PMID- 18048705
TI  - Sexual health--what are users' views?

PMID- 18048704
TI  - Vitamin C may affect lung infections.

PMID- 18048707
TI  - Hyperglycaemia and mortality.
AB  - Several studies over the last decade have linked hyperglycaemia on hospital
      admission with subsequent mortality risk. The evidence is strongest for patients
      with myocardial infarction or acute coronary syndromes, but evidence also links
      hyperglycaemia with mortality from stroke and other medical illnesses. The effect
      seems independent of a previous diagnosis of diabetes mellitus; indeed, some
      studies suggest that mortality may be higher in patients with hyperglycaemia and
      no previous diabetes diagnosis compared with known diabetic patients. The effect
      on outcome of therapeutically lowering blood glucose levels has been considered
      in a small number of studies, but so far the results are conflicting. Further
      work is needed, focusing on more standardized surveys--previous studies vary in
      their use of blood or plasma, as well as cut-off levels for hyperglycaemia--and
      larger intervention studies.

PMID- 18048708
TI  - How and why do we measure surgical risk?

PMID- 18048709
TI  - 'A matter of faith, not science': analysis of media coverage of prostate cancer
      screening in Australian news media 2003-2006.
AB  - OBJECTIVE: Despite a near universal absence of evidence-based policies supporting
      population screening for prostate cancer, the prostate-specific antigen (PSA)
      test is aggressively promoted in the media as a life-saving form of screening.
      The objective of this study was to examine media coverage of prostate-cancer
      screening in Australia. DESIGN: Frame analysis of all direct or attributed quotes
      about prostate cancer. SETTING: Australian capital city newspapers (February 2003
      December 2006) and Sydney television news (January 2003-December 2006). MAIN
      OUTCOME MEASURES: Quotes regarding prostate cancer screening: n=436 in newspapers
      and television news. RESULTS: Seven rhetorical frames were identified. 86% of all
      quotes framed prostate screening and its outcomes as desirable, associating PSA
      testing as being consonant with other early-detection cancer-control messages.
      Adverse surgical sequelae to screening were often minimized, scientific progress
      highlighted and gender equity appeals appropriated. Those questioning screening
      were vilified, with epidemiology being framed as an inferior form of knowledge
      than clinical experience. CONCLUSIONS: Australian men are exposed to unbalanced
      and often non-evidence-based appeals to seek PSA testing. There is a disturbing
      lack of effort to redress this imbalance.

PMID- 18048710
TI  - Posterior reversible encephalopathy syndrome in (low renin) essential
      hypertension.

PMID- 18048711
TI  - Carpopedal spasm in an elderly man: an unusual presentation of coeliac disease.

PMID- 18048712
TI  - Learning how to control biases in studies to identify adverse effects of drugs.

PMID- 18048713
TI  - Please lend a hand.

PMID- 18048714
TI  - A crime against mental health?

PMID- 18048716
TI  - Proposal of Viridibacillus gen. nov. and reclassification of Bacillus arvi,
      Bacillus arenosi and Bacillus neidei as Viridibacillus arvi gen. nov., comb.
      nov., Viridibacillus arenosi comb. nov. and Viridibacillus neidei comb. nov.
AB  - A polyphasic study was undertaken to clarify the taxonomic position of endospore
      forming strains 433-D9, 433-E17 and 121-X1. BOX-PCR-generated fingerprints
      indicated that they may be members of a single species. 16S rRNA gene sequence
      similarity demonstrated that a representative of this group, 433-D9, is
      affiliated closely with Bacillus arvi DSM 16317(T) (100 %), Bacillus arenosi DSM
      16319(T) (99.8 %) and Bacillus neidei NRRL BD-87(T) (97.1 %). Sequence
      similarities revealed Bacillus pycnus NRRL NRS-1691(T) and several Kurthia
      species as the next nearest relatives. DNA-DNA hybridization results showed that
      strain 433-D9 is a member of B. arvi. Detection of l-Lys-d-Asp-based
      peptidoglycan in strain 433-D9, B. arvi DSM 16317(T) and B. arenosi DSM 16319(T)
      was in agreement with their close relationship, but differentiated these strains
      from B. neidei NRRL BD-87(T) and B. pycnus NRRL NRS-1691(T), for which l-Lys-d
      Glu was reported. A similar quinone system was detected in strains 433-D9, 433
      E17, 121-X1, B. arvi DSM 16317(T), B. arenosi DSM 16319(T) and B. neidei NRRL BD
      87(T). This system, unusual for bacilli, consisted of the major compound
      menaquinone MK-8 (69-80 %) and moderate amounts of MK-7 (19-30 %). This
      observation was in contrast to the predominance of MK-7 of the closest relative
      B. pycnus NRRL NRS-1691(T), as also reported for representatives of the closely
      related non-endospore-forming genus Kurthia. Strains 433-D9, B. arvi DSM 16317(T)
      and B. arenosi DSM 16319(T) exhibited homogeneous and discriminative polar lipid
      profiles and fatty acid profiles consisting of major acids i-C(15 : 0) and ai
      C(15 : 0) and moderate amounts of i-C(17 : 1)omega10c and i-C(17 : 1) I/ai-C(17 :
      1) B that discriminated them from closely related strains such as B. neidei NRRL
      BD-87(T). On the basis of clear-cut discriminative chemotaxonomic markers, we
      propose strains 433-D9, 433-E17 and 121-X1, B. arvi DSM 16317(T), B. arenosi DSM
      16319(T) and B. neidei NRRL BD-87(T) to be reclassified within a separate genus.
      For this new taxon, we propose the name Viridibacillus gen. nov., and we propose
      the reclassification of Bacillus arvi, Bacillus arenosi and Bacillus neidei as
      Viridibacillus arvi gen. nov., comb. nov. (the type species of Viridibacillus,
      with the type strain DSM 16317(T) =LMG 22165(T)), Viridibacillus arenosi comb.
      nov. (type strain DSM 16319(T) =LMG 22166(T)) and Viridibacillus neidei comb.
      nov. (type strain NRRL BD-87(T) =DSM 15031(T) =JCM 11077(T)).

PMID- 18048717
TI  - Salegentibacter salarius sp. nov., isolated from a marine solar saltern.
AB  - A Gram-negative, non-motile, rod-shaped bacterium, strain ISL-6(T),
      phenotypically resembling members of the genus Salegentibacter, was isolated from
      a marine solar saltern of the Yellow Sea in Korea and subjected to a polyphasic
      taxonomic investigation. Strain ISL-6(T) grew optimally at pH 7.0-8.0 and 30
      degrees C and in the presence of 8 % (w/v) NaCl. It contained MK-6 as the
      predominant menaquinone. The major fatty acids were iso-C(15 : 0) and anteiso
      C(15 : 0). The DNA G+C content was 37.5 mol%. A phylogenetic analysis based on
      16S rRNA gene sequences showed that strain ISL-6(T) belonged to the genus
      Salegentibacter. Strain ISL-6(T) exhibited 16S rRNA gene sequence similarity
      values of 92.0-98.6 % with respect to the type strains of recognized
      Salegentibacter species. Low DNA-DNA relatedness values, differential phenotypic
      properties and phylogenetic distinctiveness demonstrated that strain ISL-6(T) is
      distinguishable from the recognized Salegentibacter species. Therefore strain ISL
      6(T) represents a novel species of the genus Salegentibacter, for which the name
      Salegentibacter salarius sp. nov. is proposed. The type strain is ISL-6(T) (=KCTC
      12974(T) =CCUG 54355(T)).

PMID- 18048718
TI  - Jonquetella anthropi gen. nov., sp. nov., the first member of the candidate
      phylum 'Synergistetes' isolated from man.
AB  - Six clinical isolates of a hitherto unknown, strictly anaerobic, Gram-negative
      rod showing fastidious growth were subjected to a polyphasic taxonomic study,
      including phenotypic, genomic and phylogenetic feature analyses. 16S rRNA gene
      sequenced-based phylogeny revealed that the novel strains represent a homogeneous
      group distant from any recognized species in the candidate phylum
      'Synergistetes'. The novel isolates were most closely related to species of the
      genus Dethiosulfovibrio, with 88.2-88.7 % 16S rRNA gene sequence similarity.
      Large-scale chromosome structure and DNA G+C content also differentiated the
      novel strains from members of the genus Dethiosulfovibrio. The novel strains were
      asaccharolytic. Major metabolic end products in trypticase/glucose/yeast extract
      broth were acetic, lactic, succinic and isovaleric acids and the major cellular
      fatty acids iso-C(15 : 0) and C(16 : 0). Based on the data presented here, a new
      genus, Jonquetella gen. nov., is proposed with one novel species, Jonquetella
      anthropi sp. nov. J. anthropi is the first characterized species of the candidate
      phylum 'Synergistetes' that includes human isolates. The G+C content of the DNA
      of the type strain of J. anthropi ADV 126(T) (=AIP 136.05(T)=CIP 109408(T)=CCUG
      53819(T)) is 59.4 mol%.

PMID- 18048719
TI  - Tetrasphaera remsis sp. nov., isolated from the Regenerative Enclosed Life
      Support Module Simulator (REMS) air system.
AB  - Two Gram-positive, coccoid, non-spore-forming bacteria (strains 3-M5-R-4(T) and 3
      M5-R-7), cells of which formed diploid, tetrad and cluster arrangements, were
      isolated from air of the Regenerative Enclosed Life Support Module Simulator
      system. On the basis of 16S rRNA gene sequence similarity, these strains were
      shown to belong to the family Intrasporangiaceae and were related to members of
      the genus Tetrasphaera, with similarities to the seven known species of the genus
      Tetrasphaera of 96.71-97.76 %. The fatty acid profile supported affiliation of
      these novel isolates to the genus Tetrasphaera, although larger amounts of
      octadecanoic acid (C(18 : 0)) and cis-9-octadecenoic acid (C(18 : 1)) were
      observed in the isolates, thus enabling them to be differentiated from other
      Tetrasphaera species. In addition, DNA-DNA hybridization studies indicated that
      these strains belonged to a novel species that could be readily distinguished
      from its nearest neighbour, Tetrasphaera japonica DSM 13192(T), which had less
      than 20 % DNA-DNA relatedness. Physiological and biochemical tests showed few
      phenotypic differences, but genotypic analysis enabled these gelatin-liquefying
      strains to be differentiated from the seven Tetrasphaera species. The strains
      described in this study therefore represent a novel species, for which the name
      Tetrasphaera remsis sp. nov. is proposed; the type strain is 3-M5-R-4(T) (=ATCC
      BAA-1496(T) =CIP 109413(T)).

PMID- 18048720
TI  - Rhodococcus qingshengii sp. nov., a carbendazim-degrading bacterium.
AB  - A Gram-positive, aerobic, non-motile, mesophilic strain, djl-6(T), able to
      degrade carbendazim, was isolated from a carbendazim-contaminated soil sample
      from Jiangsu province, China. The taxonomic position of this isolate was analysed
      by using a polyphasic approach. Chemotaxonomic analysis including peptidoglycan
      type, diagnostic sugar composition, fatty acid profile, menaquinones, polar
      lipids and mycolic acids showed that the characteristics of strain djl-6(T) were
      in good agreement with those of the genus Rhodococcus. DNA-DNA hybridization
      showed that it had low genomic relatedness with Rhodococcus baikonurensis DSM
      44587(T) (31.8 %), Rhodococcus erythropolis DSM 43066(T) (23.8 %) and Rhodococcus
      globerulus DSM 43954(T) (17.7 %), the three type strains to which strain djl-6(T)
      was most closely related based on 16S rRNA gene sequence analysis (99.78, 99.25
      and 98.91 % similarity, respectively). Based on the phenotypic properties and DNA
      DNA hybridization data, strain djl-6(T) (=CGMCC 1.6580(T) =KCTC 19205(T)) is
      proposed as the type strain of a novel Rhodococcus species, Rhodococcus
      qingshengii sp. nov.

PMID- 18048721
TI  - Proposal of Umezawaea gen. nov., a new genus of the Actinosynnemataceae related
      to Saccharothrix, and transfer of Saccharothrix tangerinus Kinoshita et al. 2000
      as Umezawaea tangerina gen. nov., comb. nov.
AB  - In the course of phylogenetic analyses of the taxa within the suborder
      Pseudonocardineae, it was observed that Saccharothrix tangerinus MK27-91F2(T) was
      misplaced in the genus Saccharothrix. After a detailed examination of nucleotide
      signatures in the 16S rRNA gene sequence along with the morphological and
      chemotaxonomic characteristics of this strain, which are different from those of
      all species of Saccharothrix as well as the other genera within the suborder, it
      was concluded that this strain represents a new genus, for which the name
      Umezawaea gen. nov. is proposed. Pseudosporangia are produced on the aerial
      mycelium, the whole-cell sugar pattern consists of galactose, mannose and ribose,
      phosphatidylethanolamine, phosphatidylinositol and lyso-phosphatidylethanolamine
      are the predominant phospholipids and MK-9(H(4)) is the predominant menaquinone.
      The type species of the proposed new genus is Umezawaea tangerina gen. nov.,
      comb. nov., with the type strain MK27-91F2(T) (=NRRL B-24463(T) =DSM 44720(T)
      =FERM P-16053(T) =JCM 10302(T) =NBRC 16184(T)).

PMID- 18048722
TI  - Methylohalomonas lacus gen. nov., sp. nov. and Methylonatrum kenyense gen. nov.,
      sp. nov., methylotrophic gammaproteobacteria from hypersaline lakes.
AB  - Aerobic enrichment at 4 M NaCl, pH 7.5, with methanol as carbon and energy source
      from sediments of hypersaline chloride-sulfate lakes in Kulunda Steppe (Altai,
      Russia) resulted in the isolation of a moderately halophilic and obligately
      methylotrophic bacterium, strain HMT 1(T). The bacterium grew with methanol and
      methylamine within a pH range of 6.8-8.2 with an optimum at pH 7.5 and at NaCl
      concentrations of 0.5-4 M with an optimum at 2 M. In addition to methanol and
      methylamine, it can oxidize ethanol, formate, formaldehyde and dimethylamine.
      Carbon is assimilated via the serine pathway. The main compatible solute is
      glycine betaine. 16S rRNA gene sequence analysis placed the isolate as a new
      lineage in the family Ectothiorhodospiraceae (Gammaproteobacteria). It is
      proposed, therefore, to accommodate this bacterium within a novel genus and
      species, Methylohalomonas lacus gen. nov., sp. nov., with HMT 1(T) (=DSM 15733(T)
      =NCCB 100208(T) =UNIQEM U237(T)) as the type strain. Two strains were obtained in
      pure culture from sediments of soda lake Magadi in Kenya and the Kulunda Steppe
      (Russia) on a mineral medium at pH 10 containing 0.6 M total Na(+) using methanol
      as a substrate. Strain AMT 1(T) was enriched with methanol, while strain AMT 3
      originated from an enrichment culture with CO. The isolates are restricted
      facultative methylotrophs, capable of growth with methanol, formate and acetate
      as carbon and energy sources. With methanol, the strains grew within a broad
      salinity range from 0.3 to 3.5-4 M total Na(+), with an optimum at 0.5-1 M. The
      pH range for growth was between 8.3 and 10.5, with an optimum at pH 9.5, which
      characterized the soda lake isolates as obligate haloalkaliphiles. Carbon is
      assimilated autotrophically via the Calvin-Benson cycle. Sequence analysis of the
      gene coding for the key enzyme RuBisCO demonstrated that strain AMT 1(T)
      possessed a single cbbL gene of the 'green' form I, clustering with members of
      the family Ectothiorhodospiraceae. Analysis of the 16S rRNA gene sequence showed
      that strains AMT 1(T) and AMT 3 belong to a single species that forms a separate
      lineage within the family Ectothiorhodospiraceae. On the basis of phenotypic and
      genetic data, the novel haloalkaliphilic methylotrophs are described as
      representing a novel genus and species, Methylonatrum kenyense gen. nov., sp.
      nov. (type strain AMT 1(T) =DSM 15732(T) =NCCB 100209(T) =UNIQEM U238(T)).

PMID- 18048723
TI  - Leucobacter chromiireducens subsp. solipictus subsp. nov., a pigmented bacterium
      isolated from the nematode Caenorhabditis elegans, and emended description of L.
      chromiireducens.
AB  - A yellow-pigmented, Gram-positive, aerobic, non-motile, non-spore-forming,
      irregular rod-shaped bacterium (strain TAN 31504(T)) was isolated from the
      bacteriophagous nematode Caenorhabditis elegans. Based on 16S rRNA gene sequence
      similarity, DNA G+C content of 69.5 mol%, 2,4-diaminobutyric acid in the cell
      wall peptidoglycan, major menaquinone MK-11, abundance of anteiso- and iso-fatty
      acids, polar lipids diphosphatidylglycerol and phosphatidylglycerol and a number
      of shared biochemical characteristics, strain TAN 31504(T) was placed in the
      genus Leucobacter. DNA-DNA hybridization comparisons demonstrated a 91 % DNA-DNA
      relatedness between strain TAN 31504(T) and Leucobacter chromiireducens LMG
      22506(T) indicating that these two strains belong to the same species, when the
      recommended threshold value of 70 % DNA-DNA relatedness for the definition of a
      bacterial species by the ad hoc committee on reconciliation of approaches to
      bacterial systematics is considered. Based on distinct differences in morphology,
      physiology, chemotaxonomic markers and various biochemical characteristics, it is
      proposed to split the species L. chromiireducens into two novel subspecies,
      Leucobacter chromiireducens subsp. chromiireducens subsp. nov. (type strain L
      1(T)=CIP 108389(T)=LMG 22506(T)) and Leucobacter chromiireducens subsp.
      solipictus subsp. nov. (type strain TAN 31504(T)=DSM 18340(T)=ATCC BAA-1336(T)).

PMID- 18048725
TI  - Arenimonas malthae sp. nov., a gammaproteobacterium isolated from an oil
      contaminated site.
AB  - A Gram-negative, rod-shaped bacterium (CC-JY-1(T)) was isolated on nutrient agar
      from a soil sample collected from an oil-contaminated site located in Chyai
      county, Taiwan. 16S rRNA gene sequence analysis demonstrated that this isolate is
      unique, showing 96.7 % sequence similarity to the type strain of Arenimonas
      donghaensis and similarities of 93.0-93.8 % to species of the genera Thermomonas,
      Lysobacter and Silanimonas. The presence of ubiquinone Q-8, a polar lipid profile
      consisting of the major compounds diphosphatidylglycerol, phosphatidylglycerol
      and phosphatidylethanolamine and the fatty acid profile were in accordance with
      the phylogenetic affiliation of CC-JY-1(T). DNA-DNA reassociation experiments
      between CC-JY-1(T) and A. donghaensis KACC 11381(T) resulted in a mean
      relatedness value of 32 %, indicating that strain CC-JY1(T) represents a novel
      species in the genus Arenimonas, for which we propose the name Arenimonas malthae
      sp. nov. The type strain is CC-JY-1(T) (=CCUG 53596(T) =CIP 109310(T)).

PMID- 18048724
TI  - Identification of lactobacilli by pheS and rpoA gene sequence analyses.
AB  - The aim of this study was to evaluate the use of the phenylalanyl-tRNA synthase
      alpha subunit (pheS) and the RNA polymerase alpha subunit (rpoA) partial gene
      sequences for species identification of members of the genus Lactobacillus. Two
      hundred and one strains representing the 98 species and 17 subspecies were
      examined. The pheS gene sequence analysis provided an interspecies gap, which in
      most cases exceeded 10 % divergence, and an intraspecies variation of up to 3 %.
      The rpoA gene sequences revealed a somewhat lower resolution, with an
      interspecies gap normally exceeding 5 % and an intraspecies variation of up to 2
      %. The combined use of pheS and rpoA gene sequences offers a reliable
      identification system for nearly all species of the genus Lactobacillus. The pheS
      and rpoA gene sequences provide a powerful tool for the detection of potential
      novel Lactobacillus species and synonymous taxa. In conclusion, the pheS and rpoA
      gene sequences can be used as alternative genomic markers to 16S rRNA gene
      sequences and have a higher discriminatory power for reliable identification of
      species of the genus Lactobacillus.

PMID- 18048726
TI  - Lapillicoccus jejuensis gen. nov., sp. nov., a novel actinobacterium of the
      family Intrasporangiaceae, isolated from stone.
AB  - A novel, yellow-pigmented actinobacterium was isolated from a small stone
      collected in Jeju, Republic of Korea. The cells of the organism, designated
      strain R-Ac013(T), were Gram-positive, aerobic, non-motile cocci that occurred
      singly or in pairs. The strain showed growth at 10-37 degrees C and pH 4.1-11.1,
      and tolerated 2 % NaCl. On the basis of the 16S rRNA gene sequence, the organism
      was phylogenetically related to members of the genera Tetrasphaera (94.6-97.1 %
      sequence similarity), Terrabacter (96.5 %), Knoellia (96.4 %), Terracoccus (96.4
      %), Oryzihumus (96.4 %), Janibacter (96.1-96.4 %) and Intrasporangium (96.2 %).
      The chemotaxonomic results for the organism were as follows: ll-diaminopimelic
      acid as the diagnostic diamino acid in the peptidoglycan, acetyl-type murein, MK
      8(H(4)) as the major menaquinone, a DNA G+C content of 74.1 mol%, and a polar
      lipid profile that comprised diphosphatidylglycerol and phosphatidylinositol. The
      fatty acid profile consisted of iso- and anteiso-methyl-branched, straight-chain
      saturated and monounsaturated types, the major components being iso-C(16 : 0),
      C(17 : 1)omega8c and iso-C(15 : 0). The combination of the phenotypic and
      phylogenetic data revealed that this strain represents a novel genus and species
      of the family Intrasporangiaceae, for which the name Lapillicoccus jejuensis gen.
      nov., sp. nov. is proposed. The type strain is strain R-Ac013(T) (=KCTC
      19200(T)=DSM 18607(T)).

PMID- 18048727
TI  - Micromonospora lupini sp. nov. and Micromonospora saelicesensis sp. nov.,
      isolated from root nodules of Lupinus angustifolius.
AB  - A study was conducted to determine the taxonomic status of six actinomycete
      strains isolated from root nodules of Lupinus angustifolius. The strains were
      filamentous, Gram-positive and produced single spores at the tip of the hyphae.
      Phylogenetic, chemotaxonomic and morphological analyses demonstrated that all six
      strains belonged to the genus Micromonospora. According to the 16S rRNA gene
      sequence data, the strains were divided into two clusters that are moderately
      related to Micromonospora mirobrigensis, Micromonospora matsumotoense and
      Micromonospora purpureochromogenes. Fatty acid patterns also supported the
      division of the strains, and significant differences between the two groups were
      found in the amounts of iso-15 : 0, iso-16 : 0, iso-16 : 1 and iso-17 : 0.
      Furthermore, the two groups showed physiological differences which included
      utilization of arabinose, trehalose, alanine and sucrose and xylan hydrolysis.
      Finally, DNA-DNA hybridization and ribotyping studies confirmed that each group
      represents a novel species. Based on the genotypic and phenotypic data, the novel
      species Micromonospora lupini sp. nov. (type strain Lupac 14N(T) =DSM 44874(T)
      =LMG 24055(T)) and Micromonospora saelicesensis sp. nov. (type strain Lupac 09(T)
      =DSM 44871(T) =LMG 24056(T)) are proposed.

PMID- 18048728
TI  - Azospirillum zeae sp. nov., a diazotrophic bacterium isolated from rhizosphere
      soil of Zea mays.
AB  - Two free-living nitrogen-fixing bacterial strains, N6 and N7(T), were isolated
      from corn rhizosphere. A polyphasic taxonomic approach, including morphological
      characterization, Biolog analysis, DNA-DNA hybridization, and 16S rRNA, cpn60 and
      nifH gene sequence analysis, was taken to analyse the two strains. 16S rRNA gene
      sequence analysis indicated that strains N6 and N7(T) both belonged to the genus
      Azospirillum and were closely related to Azospirillum oryzae (98.7 and 98.8 %
      similarity, respectively) and Azospirillum lipoferum (97.5 and 97.6 % similarity,
      respectively). DNA-DNA hybridization of strains N6 and N7(T) showed reassociation
      values of 48 and 37 %, respectively, with A. oryzae and 43 % with A. lipoferum.
      Sequences of the nifH and cpn60 genes of both strains showed 99 and approximately
      95 % similarity, respectively, with those of A. oryzae. Chemotaxonomic
      characteristics (Q-10 as quinone system, 18 : 1omega7c as major fatty acid) and
      G+C content of the DNA (67.6 mol%) were also similar to those of members of the
      genus Azospirillum. Gene sequences and Biolog and fatty acid analysis showed that
      strains N6 and N7(T) differed from the closely related species A. lipoferum and
      A. oryzae. On the basis of these results, it is proposed that these nitrogen
      fixing strains represent a novel species. The name Azospirillum zeae sp. nov. is
      suggested, with N7(T) (=NCCB 100147(T)=LMG 23989(T)) as the type strain.

PMID- 18048729
TI  - Rhodanobacter ginsengisoli sp. nov. and Rhodanobacter terrae sp. nov., isolated
      from soil cultivated with Korean ginseng.
AB  - Two bacterial isolates from ginseng fields in Korea, strains GR17-7(T) and GP18
      1(T), were characterized using a polyphasic approach. Phylogenetic analysis of
      their 16S rRNA gene sequences revealed a clear affiliation with the
      Gammaproteobacteria, and showed that the closest phylogenetic relationships were
      with members of the genus Rhodanobacter. The 16S rRNA gene sequence similarity
      between strains GR17-7(T) and GP18-1(T) was 97.2 %. Both strains showed 16S rRNA
      gene sequence similarities of 95.2-96.9 % to type strains of recognized
      Rhodanobacter species. The G+C contents of the DNA of strains GR17-7(T) and GP18
      1(T) were 61.0 and 62.5 mol%, respectively. According to the DNA-DNA
      hydridization tests, the hybridization value between strains GR17-7(T) and GP18
      1(T) was 34 %. Strains GR17-7(T) and GP18-1(T) showed less than 32 % DNA-DNA
      relatedness with Rhodanobacter fulvus KCTC 12098(T) and Rhodanobacter
      spathiphylli LMG 23181(T). Strains GR17-7(T) and GP18-1(T) were aerobic, Gram
      negative, rod-shaped, and catalase- and oxidase-positive. Major fatty acids of
      both strains were iso-C(17 : 1)omega9c and iso-C(16 : 0). Based on the data
      presented, two novel Rhodanobacter species are proposed, with the names
      Rhodanobacter ginsengisoli sp. nov. (type strain GR17-7(T)=KACC 11762(T)=DSM
      18993(T)) and Rhodanobacter terrae sp. nov. (type strain GP18-1(T)=KACC
      11761(T)=DSM 19241(T)).

PMID- 18048730
TI  - Lewinella agarilytica sp. nov., a novel marine bacterium of the phylum
      Bacteroidetes, isolated from beach sediment.
AB  - A Gram-negative, aerobic, light-orange-coloured, marine bacterium (designated SST
      19(T)) was isolated from beach sediment in Jeju, Korea, and its taxonomic
      position was determined by means of a polyphasic approach. In a neighbour-joining
      phylogenetic tree based on 16S rRNA gene sequences, strain SST-19(T) was
      positioned within the family 'Saprospiraceae', class Sphingobacteria, and formed
      a consistent cluster with Lewinella persica ATCC 23167(T) (94.7 % sequence
      similarity). The levels of 16S rRNA gene sequence similarity between the isolate
      and recognized members of the family ranged from 84 to 89 %, with Lewinella
      cohaerens ATCC 23123(T), Lewinella nigricans ATCC 23147(T), Haliscomenobacter
      hydrossis DSM 1100(T) and Saprospira grandis ATCC 23119(T) showing values of 89.0
      , 88.4 , 86.4 and 84.1 %, respectively. Strain SST-19(T) required seawater for
      growth and its cells were unbranched, flexible rods or filaments with gliding
      motility. The cellular fatty acids consisted mainly of saturated, unsaturated and
      iso-branched fatty acids, the major components being C(16 : 1)omega7c and/or iso
      C(15 : 0) 2-OH (24.1 %), C(18 : 0) (13.5 %), iso-C(15 : 0) (11.1 %) and C(16 : 0)
      (10.9 %). The G+C content of the DNA was found to be 51.3 mol%. On the basis of
      the results from phenotypic and phylogenetic analyses, the isolate represents a
      novel species of the genus Lewinella, for which the name Lewinella agarilytica
      sp. nov. is proposed. The type strain is SST-19(T) (=JBRI 2009(T)=KCTC
      12774(T)=JCM 14216(T)).

PMID- 18048731
TI  - Lechevalieria xinjiangensis sp. nov., a novel actinomycete isolated from
      radiation-polluted soil in China.
AB  - A novel actinomycete was isolated from radiation-polluted soil collected from
      Xinjiang in north-western China. The isolate, strain R24(T), was found to have
      chemical and morphological properties associated with members of the genus
      Lechevalieria. An almost-complete 16S rRNA gene sequence of the isolate was
      aligned with corresponding sequences from representatives of the genus
      Lechevalieria and related taxa, using three tree-making algorithms, and was shown
      to form a distinct phyletic line in the Lechevalieria phylogenetic tree. DNA-DNA
      relatedness and phenotypic data served to distinguish strain R24(T) from members
      of the three Lechevalieria species with validly published names. The genotypic
      and phenotypic data show that the isolate should be classified as a novel species
      within the genus Lechevalieria. The name proposed for this taxon is Lechevalieria
      xinjiangensis sp. nov. The type strain is R24(T) (=CGMCC 4.3525(T)=DSM 45081(T)).

PMID- 18048732
TI  - Reclassification of Vibrio fischeri, Vibrio logei, Vibrio salmonicida and Vibrio
      wodanis as Aliivibrio fischeri gen. nov., comb. nov., Aliivibrio logei comb.
      nov., Aliivibrio salmonicida comb. nov. and Aliivibrio wodanis comb. nov.
AB  - Four closely related species, Vibrio fischeri, Vibrio logei, Vibrio salmonicida
      and Vibrio wodanis, form a clade within the family Vibrionaceae; the taxonomic
      status and phylogenetic position of this clade have remained ambiguous for many
      years. To resolve this ambiguity, we tested these species against other species
      of the Vibrionaceae for phylogenetic and phenotypic differences. Sequence
      identities for the 16S rRNA gene were > or =97.4 % among members of the V.
      fischeri group, but were < or =95.5 % for members of this group in comparison
      with type species of other genera of the Vibrionaceae (i.e. Photobacterium and
      Vibrio, with which they overlap in G+C content, and Enterovibrio, Grimontia and
      Salinivibrio, with which they do not overlap in G+C content). Combined analysis
      of the recA, rpoA, pyrH, gyrB and 16S rRNA gene sequences revealed that the
      species of the V. fischeri group form a tightly clustered clade, distinct from
      these other genera. Furthermore, phenotypic traits differentiated the V. fischeri
      group from other genera of the Vibrionaceae, and a panel of 13 biochemical tests
      discriminated members of the V. fischeri group from type strains of
      Photobacterium and Vibrio. These results indicate that the four species of the V.
      fischeri group represent a lineage within the Vibrionaceae that is distinct from
      other genera. We therefore propose their reclassification in a new genus,
      Aliivibrio gen. nov. Aliivibrio is composed of four species: Aliivibrio fischeri
      comb. nov. (the type species) (type strain ATCC 7744(T) =CAIM 329(T) =CCUG
      13450(T) =CIP 103206(T) =DSM 507(T) =LMG 4414(T) =NCIMB 1281(T)), Aliivibrio
      logei comb. nov. (type strain ATCC 29985(T) =CCUG 20283(T) =CIP 104991(T) =NCIMB
      2252(T)), Aliivibrio salmonicida comb. nov. (type strain ATCC 43839(T) =CIP
      103166(T) =LMG 14010(T) =NCIMB 2262(T)) and Aliivibrio wodanis comb. nov. (type
      strain ATCC BAA-104(T) =NCIMB 13582(T) =LMG 24053(T)).

PMID- 18048733
TI  - Reclassification of Aquaspirillum itersonii and Aquaspirillum peregrinum as
      Novispirillum itersonii gen. nov., comb. nov. and Insolitispirillum peregrinum
      gen. nov., comb. nov.
AB  - Phylogenetic analysis based on 16S rRNA gene sequences showed that Aquaspirillum
      itersonii and Aquaspirillum peregrinum form distinct phylogenetic lineages within
      the Alphaproteobacteria, whereas Aquaspirillum serpens, the type species of the
      genus Aquaspirillum, belongs to the Betaproteobacteria. A. itersonii and A.
      peregrinum exhibited 16S rRNA gene sequence similarity values of 82.0-82.4 % to
      the type strain of A. serpens and of 91.8-92.0 % to each other. A. itersonii and
      A. peregrinum were clearly distinguishable from A. serpens by differences in
      ubiquinone types and fatty acid profiles. A. itersonii subsp. itersonii LMG
      4337(T) and A. itersonii subsp. nipponicum LMG 7370(T) contained Q-10 as the
      predominant ubiquinone, and A. peregrinum subsp. peregrinum LMG 4340(T) and A.
      peregrinum subsp. integrum LMG 5407(T) contained Q-9 as the predominant
      ubiquinone, whereas A. serpens LMG 3734(T) had Q-8 as the predominant ubiquinone.
      A. itersonii and A. peregrinum were also distinguishable from A. serpens by some
      differences in the fatty acid composition, including major fatty acids and
      hydroxy fatty acids. On the basis of these data, A. itersonii and A. peregrinum
      should be reclassified into two novel genera and species, for which the names
      Novispirillum itersonii gen. nov., comb. nov. and Insolitispirillum peregrinum
      gen. nov., comb. nov., respectively, are proposed.

PMID- 18048734
TI  - Lactobacillus hayakitensis sp. nov., isolated from intestines of healthy
      thoroughbreds.
AB  - Two strains, KBL13(T) and GBL13, were isolated as one of intestinal lactobacilli
      from the faecal specimens from different thoroughbreds of the same farm where
      they were born in Hokkaido, Japan. They were Gram-positive, facultatively
      anaerobic, catalase-negative, non-spore-forming and non-motile rods. KBL13(T) and
      GBL13 homofermentatively metabolize glucose, and produce lactate as the sole
      final product from glucose. The 16S rRNA gene sequence, DNA-DNA hybridization,
      DNA G+C content and biochemical characterization indicated that these two
      strains, KBL13(T) and GBL13, belong to the same species. In the representative
      strain, KBL13(T), the DNA G+C content was 34.3 mol%. Lactobacillus salivarius JCM
      1231(T) (=ATCC 11741(T); AF089108) is the type strain most closely related to the
      strain KBL13(T) as shown in the phylogenetic tree, and the 16S rRNA gene sequence
      identity showed 96.0 % (1425/1484 bp). Comparative 16S rRNA gene sequence
      analysis of this strain indicated that the two isolated strains belong to the
      genus Lactobacillus and that they formed a branch distinct from their closest
      relatives, L. salivarius, Lactobacillus aviarius, Lactobacillus saerimneri and
      Lactobacillus acidipiscis. DNA-DNA reassociation experiments with L. salivarius
      and L. aviarius confirmed that KBL13(T) represents a novel species, for which the
      name Lactobacillus hayakitensis sp. nov. is proposed. The type strain is KBL13(T)
      (=JCM 14209(T)=DSM 18933(T)).

PMID- 18048735
TI  - Maribacter polysiphoniae sp. nov., isolated from a red alga.
AB  - A novel gliding, heterotrophic, Gram-negative, yellow-orange-pigmented, aerobic,
      oxidase- and catalase-positive bacterium, designated strain KMM 6151(T), was
      isolated from the Pacific red alga Polysiphonia japonica. Analysis of the 16S
      rRNA gene sequence of the strain revealed that it formed a distinct lineage
      within the genus Maribacter, family Flavobacteriaceae, with sequence similarities
      in the range 94.6-96.9 %. On the basis of phenotypic, genotypic and phylogenetic
      data, strain KMM 6151(T) represents a novel species of the genus Maribacter, for
      which the name Maribacter polysiphoniae sp. nov. is proposed. The type strain is
      KMM 6151(T) (=KCTC 22021(T)=LMG 23671(T)).

PMID- 18048736
TI  - Veillonella denticariosi sp. nov., isolated from human carious dentine.
AB  - Selective culture of human carious dentine for Veillonella strains resulted in
      the isolation of two strains of a Gram-negative, coccus-shaped bacterium that has
      not been described previously. Comparative 16S rRNA and dnaK gene sequence
      analysis indicated that the two strains were homogeneous and comprised a distinct
      lineage within the genus Veillonella, phylogenetically most closely related to
      Veillonella rodentium. This was supported by DNA-DNA hybridization, which showed
      clearly that the two strains were similar and distinct from other Veillonella
      species, and the production of major cellular fatty acids (C(13 : 0) and C(17 :
      1)omega8), which is consistent with other members of the genus Veillonella. Based
      on these observations, strains RBV81 and RBV106(T) represent a novel species, for
      which the name Veillonella denticariosi sp. nov. is proposed, with the type
      strain RBV106(T) (=CIP 109448(T) =CCUG 54362(T) =DSM 19009(T)).

PMID- 18048737
TI  - Methylobacterium platani sp. nov., isolated from a leaf of the tree Platanus
      orientalis.
AB  - A novel bacterial strain, designated PMB02(T), was isolated from a leaf of the
      tree Platanus orientalis. Colonies grown on TYG agar plates were circular, pink
      pigmented and slow-growing, being 0.2-1.5 mm in diameter after 3 days growth. The
      cells of strain PMB02(T) were Gram-negative, aerobic, motile rods that possessed
      oxidase and catalase activities and grew at 20-30 degrees C, pH 6-8 and in media
      containing less than 1 % NaCl. The major respiratory quinone was identified as Q
      10. A phylogenetic analysis based on 16S rRNA gene sequence comparisons indicated
      that strain PMB02(T) was related to members of the genus Methylobacterium. A
      comparative 16S rRNA gene sequence-based phylogenetic analysis placed the strain
      in a clade with the species Methylobacterium aquaticum and Methylobacterium
      variabile, with which it showed sequence similarities of 97.7 and 97.4 %,
      respectively. The values for DNA-DNA hybridization between strain PMB02(T) and M.
      aquaticum CCM 7218(T) and M. variabile GR3(T) were less than 32 %. On the basis
      of the phenotypic characterization, the phylogenetic analysis and the DNA-DNA
      relatedness data, strain PMB02(T) is considered to represent a novel species of
      the genus Methylobacterium, for which the name Methylobacterium platani sp. nov.
      is proposed. The type strain is PMB02(T) (=KCTC 12901(T)=JCM 14648(T)).

PMID- 18048738
TI  - Chitinilyticum aquatile gen. nov., sp. nov., a chitinolytic bacterium isolated
      from a freshwater pond used for Pacific white shrimp culture.
AB  - Strain c14(T), originally isolated from surface water of a freshwater pond
      located in Pingtung (southern Taiwan) used for culture of Pacific white shrimp
      (Litopenaeus vannamei), was subjected to a polyphasic taxonomic approach. The
      strain exhibited strong chitinolytic activity and was able to grow under aerobic
      and anaerobic conditions by utilizing chitin exclusively as the carbon, nitrogen
      and energy source. Phylogenetic analysis of the 16S rRNA gene sequence revealed a
      clear affiliation of the proposed bacterium to the Betaproteobacteria, most
      closely related to Chitinibacter tainanensis S1(T), Deefgea rivuli WB 3.4-79(T)
      and Silvimonas terrae KM-45(T), with 94.6, 93.6 and 92.9 % 16S rRNA gene sequence
      similarity, respectively. The predominant fatty acids detected in cells of strain
      c14(T) were C(16 : 0), C(18 : 1)omega7c and summed feature 3 (C(16 : 1)omega7c
      and/or C(15 : 0) iso 2-OH). The G+C content of the genomic DNA was 69.5 (+/-1.0)
      mol%. Biochemical, physiological, chemotaxonomic and phylogenetic analyses showed
      that strain c14(T) could not be assigned to any known genus of the
      Betaproteobacteria. Therefore, strain c14(T) is classified within a novel genus
      and species, for which the name Chitinilyticum aquatile gen. nov., sp. nov. is
      proposed. The type strain of Chitinilyticum aquatile is c14(T) (=LMG 23346(T)
      =BCRC 17533(T)).

PMID- 18048739
TI  - Knoellia aerolata sp. nov., isolated from an air sample in Korea.
AB  - An aerobic, Gram-positive, non-motile, non-spore-forming, rod-coccus-shaped
      bacterium, strain 5317S-21(T), was isolated from an air sample from Suwon city,
      Republic of Korea. The isolate was able to grow within a pH range of 5.0-9.0 and
      a temperature range of 5-35 degrees C and it tolerated up to 2 % (w/v) NaCl. The
      cell-wall peptidoglycan contained meso-diaminopimelic acid as diagnostic diamino
      acid. The predominant isoprenoid quinone was MK-8(H(4)). The major polar lipids
      were phosphatidylinositol, phosphatidylethanolamine and diphosphatidylglycerol;
      phosphatidylglycerol and several unknown phospholipids were also detected.
      Mycolic acids were absent. The only whole-cell sugar was glucose. The major
      cellular fatty acids were iso-C(16 : 0), C(17 : 1)omega8c and iso-C(15 : 0). 16S
      rRNA gene sequence analysis indicated that strain 5317S-21(T) was related
      phylogenetically to members of the genus Knoellia, with 97.4 % sequence
      similarity to the type strains of Knoellia sinensis and Knoellia subterranea. The
      G+C content of the genomic DNA of strain 5317S-21(T) was 73 mol%. Levels of DNA
      DNA relatedness between strain 5317S-21(T) and the type strains of Knoellia
      sinensis and Knoellia subterranea were 37 and 41 %, respectively. It was
      concluded that strain 5317S-21(T) represents a novel species of the genus
      Knoellia, for which the name Knoellia aerolata sp. nov. is proposed. The type
      strain is 5317S-21(T) (=KACC 20583(T) =DSM 18566(T)).

PMID- 18048740
TI  - Desulfotignum toluenicum sp. nov., a novel toluene-degrading, sulphate-reducing
      bacterium isolated from an oil-reservoir model column.
AB  - A Gram-negative, sulphate-reducing bacterium (strain H3(T)) was isolated from an
      oil-reservoir model column. The new isolate was able to oxidize toluene coupled
      to hydrogen sulphide production. For growth, the optimum salt concentration was
      1.5 % (w/v), the optimum pH was 7.2 and the optimum temperature was 34 degrees C.
      The cells were straight to slightly curved rods, 0.6-1.0 microm in diameter and
      1.4-2.5 microm in length. The predominant fatty acids were C(16 : 0), C(16 :
      1)omega7c and C(17 : 0) cyclo, and the cells also contained dimethylacetals.
      Cloning and sequencing of a 1505 bp long fragment of the 16S rRNA gene showed
      that strain H3(T) is a member of the Deltaproteobacteria and is related closely
      to Desulfotignum balticum DSM 7044(T). The G+C content of the DNA was 52.0 mol%
      and the DNA-DNA similarity to D. balticum DSM 7044(T) was 56.1 %. Based on
      differences in DNA sequence and the unique property of toluene degradation, it is
      proposed that strain H3(T) should be designated a member of a novel species
      within the genus Desulfotignum, for which the name Desulfotignum toluenicum sp.
      nov. is proposed. The type strain is H3(T) (=DSM 18732(T)=ATCC BAA-1460(T)).

PMID- 18048741
TI  - Spirosoma rigui sp. nov., isolated from fresh water.
AB  - A Gram-negative, yellow-pigmented bacterium capable of gliding motility,
      designated strain WPCB118(T), was isolated from fresh water collected from the
      Woopo wetland (Republic of Korea). Cells were rod-shaped and sometimes
      filamentous. The major fatty acids were iso-C(15 : 0) 2-OH and/or C(16 :
      1)omega7c (45.6 %), C(16 : 1)omega5c (18.5 %), iso-C(15 : 0) (9.5 %) and C(16 :
      0) (8.8 %). The predominant menaquinone and polar lipid were MK-7 and
      phosphatidylethanolamine, respectively. The DNA G+C content was 53.3 mol%. A
      phylogenetic tree based on 16S rRNA gene sequences showed that strain WPCB118(T)
      had an evolutionary lineage within the radiation encompassing the members of the
      family 'Flexibacteraceae', its closest neighbour being Spirosoma linguale LMG
      10896(T) (93.7 % gene sequence similarity). Data from this polyphasic study
      indicated that strain WPCB118(T) could not be assigned to any recognized species.
      Strain WPCB118(T) represents a novel species of the genus Spirosoma, for which
      the name Spirosoma rigui sp. nov. is proposed. The type strain is WPCB118(T)
      (=KCTC 12531(T)=NBRC 101117(T)).

PMID- 18048742
TI  - Pelagicoccus croceus sp. nov., a novel marine member of the family
      Puniceicoccaceae within the phylum 'Verrucomicrobia' isolated from seagrass.
AB  - An obligately aerobic, spherical, non-motile, pale-yellow pigmented bacterium was
      isolated from a piece of leaf of seagrass, Enhalus acoroides (L.f.) Royle, grown
      in Okinawa, Japan and was subjected to a polyphasic taxonomic study. Phylogenetic
      analyses based on 16S rRNA gene sequences revealed that the novel isolate N5FB36
      5(T) shared approximately 96-98 % sequence similarity with the species of the
      genus Pelagicoccus of the family Puniceicoccaceae within the phylum
      'Verrucomicrobia'. The DNA-DNA relatedness values of strain N5FB36-5(T) with
      Pelagicoccus mobilis 02PA-Ca-133(T) and Pelagicoccus albus YM14-201(T) were below
      70 %, which is accepted as the phylogenetic definition of a novel species. beta
      Lactam antibiotic susceptibility test and amino acid analysis of the cell wall
      hydrolysates indicated the absence of muramic acid and diaminopimelic acid in the
      cell walls, which suggested that this strain lacks an ordinary Gram-negative type
      of peptidoglycan in the cell wall. The DNA G+C content of strain N5FB36-5(T) was
      51.6 mol%; MK-7 was the major menaquinone; and the presence of C(16 : 0), C(16 :
      1)omega7c and anteiso-C(15 : 0) as the major cellular fatty acids supported the
      identification of the novel isolate as a member of the genus Pelagicoccus. On the
      basis of polyphasic taxonomic data, it was concluded that this strain should be
      classified as a novel species of the genus Pelagicoccus, for which the name
      Pelagicoccus croceus sp. nov. is proposed. The type strain is N5FB36-5(T)
      (=MBIC08283(T)=KCTC [corrected] 12903(T)).

PMID- 18048743
TI  - Phylogenetic analysis of Xanthomonas species by comparison of partial gyrase B
      gene sequences.
AB  - The genus Xanthomonas currently comprises 27 species with validly published names
      that are important crop and horticultural pathogens. We have constructed a
      phylogram from alignment of gyrase B (gyrB) sequences for all xanthomonad
      species, both to indicate inter-species relatedness and as an aid for rapid and
      accurate species-level identification. The phylogeny indicated a monophyletic
      group, with X. albilineans and X. sacchari as the most ancestral species. Three
      species, X. hyacinthi, X. translucens and X. theicola, formed an early-branching
      group. Three clades were supported by high bootstrap values: group 1 comprised X.
      cucurbitae, X. cassavae and X. codiaei; group 2 comprised X. arboricola, X.
      campestris, X. populi, X. hortorum, X. gardneri and X. cynarae; group 3 contained
      the remaining species, within which two further clades, supported by a 100 %
      bootstrap value, were identified. Group 3A comprised X. axonopodis, X.
      euvesicatoria, X. perforans and X. melonis, together with X. alfalfae, X. citri
      and X. fuscans, whose names were recently validly published. Group 3B contained
      the monocot pathogens X. vasicola and X. oryzae. Two recently identified species,
      X. cynarae and X. gardneri, were poorly discriminated and were related closely to
      X. hortorum. Three species, X. perforans, X. euvesicatoria and X. alfalfae, had
      identical gyrB sequences. Partial sequencing of a further five genes from these
      species found only minor sequence differences that confirmed their close
      relatedness. Although branch lengths between species varied, indicating different
      degrees of genetic distinctiveness, the majority (n=21) were well-differentiated,
      indicating the utility of the method as an identification tool, and we now use
      this method for routine diagnosis of xanthomonad species.

PMID- 18048744
TI  - Bacillus plakortidis sp. nov. and Bacillus murimartini sp. nov., novel
      alkalitolerant members of rRNA group 6.
AB  - The Gram-positive, alkali- and salt-tolerant marine bacterium strain P203(T) is
      described together with its closest phylogenetic neighbour, terrestrial isolate
      LMG 21005(T). Strain P203(T) was isolated from material from the sponge Plakortis
      simplex that was obtained from the Sula-Ridge, Norwegian Sea. Strain LMG 21005(T)
      was an undescribed strain that was isolated from a church wall mural in Germany.
      Strains P203(T) and LMG 21005(T) were identified as novel alkalitolerant members
      of the Bacillus rRNA group 6 with a 16S rRNA gene sequence similarity of 99.5 %.
      The closest described neighbour, Bacillus gibsonii DSM 8722(T), showed 99.0 %
      gene sequence similarity with P203(T) and 98.8 % similarity with strain LMG
      21005(T). Despite the high 16S rRNA gene sequence similarity, DNA-DNA cross
      hybridization revealed only 25.8-34.1 % similarity amongst the three strains. The
      DNA G+C contents were 41.1 mol% for strain P203(T) and 39.6 mol% for strain LMG
      21005(T). Both strains grew well between pH 7 and pH 11. Strain P203(T) showed
      growth at moderate temperatures (from 4 to 30 degrees C) and in the presence of
      up to 12 % (w/v) NaCl at pH 9.7, whereas strain LMG 21005(T) was not salt
      tolerant (up to 4 % NaCl) and no growth was observed at 4 degrees C. The major
      fatty acids of strains P203(T), LMG 21005(T) and the type strain of B. gibsonii
      were the saturated terminally methyl-branched compounds iso-C(15 : 0) (19.8, 15.6
      and 28.0 %, respectively) and anteiso-C(15 : 0) (57.1, 48.6 and 45.2 %,
      respectively). Physiological and biochemical tests allowed genotypic and
      phenotypic differentiation of strains P203(T) and LMG 21005(T) from the six
      related Bacillus species with validly published names and supported the proposal
      of two novel species, Bacillus plakortidis [type strain P203(T) (=DSM
      19153(T)=NCIMB 14288(T))] and Bacillus murimartini [type strain LMG 21005(T)
      (=NCIMB 14102(T))].

PMID- 18048745
TI  - Probable synonymy of the nitrogen-fixing genus Azotobacter and the genus
      Pseudomonas.
AB  - The relationships of the genus Azotobacter, Azomonas macrocytogenes and the genus
      Pseudomonas were revealed by comparative analysis of partial 16S rRNA and atpD,
      carA and recA gene sequences and as concatenated nucleotide and peptide
      sequences. Sequence similarities of Azotobacter species and Azomonas
      macrocytogenes indicated that these may be considered to be synonyms at the
      molecular level. In addition, these species show an intimate relationship with
      species of Pseudomonas, especially P. aeruginosa (the type species of the genus).
      In terms of the current circumscription of the genus Pseudomonas, Azotobacter and
      Azomonas macrocytogenes should be considered for amalgamation with Pseudomonas.
      Azotobacter and Azomonas comprise nitrogen-fixing strains with large pleomorphic
      cells that form cysts, and peritrichous flagella insertion; characteristics not
      included in the current circumscription of Pseudomonas. The data are discussed in
      the light of whether lateral transfer of genes could be involved in the
      determination of significant morphological characteristics, thus leading to a
      problem that may be encountered more frequently: how to resolve classification of
      taxa based on conserved sequences with those based on their phenotype. More
      fundamentally, the results illuminate problems that will increasingly be
      encountered: by what criteria can taxa be delineated, what are the most
      appropriate methods for classification, and what are the proper assumptions of
      bacterial classification?

PMID- 18048746
TI  - Cohnella laeviribosi sp. nov., isolated from a volcanic pond.
AB  - A novel thermophilic and endospore-forming Gram-positive bacterium capable of
      assimilating and isomerizing l-ribose was isolated from a volcanic area in
      Likupang, Indonesia. The isolate, RI-39(T), was able to grow at high temperatures
      (37-60 degrees C); optimum growth was observed at pH 6.5 and 45 degrees C. The
      strain contained MK-7 (87 %) as the main respiratory quinone and had a DNA G+C
      content of 51 mol%. The major cellular fatty acids of the isolate were iso-C(16 :
      0) and anteiso-C(15 : 0) and the predominant polar lipids were
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and lysyl
      phosphatidylglycerol. Phylogenetic analysis based on 16S rRNA gene sequences
      revealed that the isolate represents an evolutionary lineage that is distinct
      from those of other Cohnella species. Based on morphological, physiological and
      chemotaxonomic characteristics and 16S rRNA gene sequence comparisons, it is
      proposed that strain RI-39(T) represents a novel species, Cohnella laeviribosi
      sp. nov. The type strain is RI-39(T) (=KCTC 3987(T) =KCCM 10653P(T) =CCUG
      52217(T)).

PMID- 18048747
TI  - Ureibacillus composti sp. nov. and Ureibacillus thermophilus sp. nov., isolated
      from livestock-manure composts.
AB  - Two Gram-negative, rod-shaped, thermophilic bacterial strains, HC145(T) and
      HC148(T), were isolated from a compost sample from a compost facility in Ichon,
      Korea. Sequencing of the 16S rRNA genes of HC145(T) and HC148(T) and comparative
      analyses of the resulting sequences clearly showed that these strains had a
      phylogenetic affiliation to the genus Ureibacillus. The level of 16S rRNA
      similarity between the two novel strains was 98.4 % and the levels of sequence
      similarity between them and existing Ureibacillus species were 97.8-98.1
      (HC145(T)) and 97.4-98.7 % (HC148(T)). The DNA-DNA reassociation values between
      the two strains and the type strains of Ureibacillus species ranged from 38 to 51
      %. The polar lipid profiles for both isolates consisted of phosphatidylglycerol,
      diphosphatidylglycerol, phospholipids and glycolipids of unknown composition. The
      major quinones were MK-8, MK-9 and MK-7, the peptidoglycan type was l-Lys<--d-Asp
      and the main cellular fatty acid was iso-C(16 : 0). The DNA G+C contents of
      strains HC145(T) and HC148(T) were 42.4 and 38.5 mol%, respectively. On the basis
      of the data from this polyphasic study, strains HC145(T) and HC148(T) represent
      members of the genus Ureibacillus, for which the names Ureibacillus composti sp.
      nov. and Ureibacillus thermophilus sp. nov., respectively, are proposed. The type
      strain of U. composti is HC145(T) (=KACC 11361(T) =DSM 17951(T)) and the type
      strain of U. thermophilus is HC148(T) (=KACC 11362(T) =DSM 17952(T)).

PMID- 18048748
TI  - Bacillus kribbensis sp. nov., isolated from a soil sample in Jeju, Korea.
AB  - A Gram-positive, endospore-forming bacterium, designated strain BT080(T), was
      isolated from a soil sample in Jeju, Korea. Cells of the isolate were strictly
      aerobic rods that were motile by means of peritrichous flagella. The strain grew
      optimally at 30-33 degrees C and pH 5.5-6.5. Chemotaxonomic data (major
      isoprenoid quinone, MK-7; DNA G+C content, 43.3 mol%; major fatty acids, anteiso
      C(15 : 0), iso-C(14 : 0), iso-C(16 : 0) and iso-C(15 : 0)) supported the
      affiliation of the isolate to the genus Bacillus. Comparative 16S rRNA gene
      sequence analyses showed that strain BT080(T) formed a distinct phyletic line
      within the genus Bacillus. The levels of 16S rRNA gene sequence similarity with
      respect to related Bacillus species were below 96.4 %. On the basis of
      physiological, biochemical and phylogenetic properties, strain BT080(T)
      represents a novel species within the genus Bacillus, for which the name Bacillus
      kribbensis sp. nov. is proposed. The type strain is BT080(T) (=KCTC 13934(T)=DSM
      17871(T)).

PMID- 18048749
TI  - Sejongia marina sp. nov., isolated from Antarctic seawater.
AB  - A Gram-negative, psychrotolerant, chemoheterotrophic, aerobic, non-gliding, non
      motile, yellow-pigmented bacterium, designated IMCC3228(T), was isolated from
      coastal seawater of the Antarctic. On the basis of 16S rRNA gene sequence
      comparisons, the strain was most closely related to the genera Sejongia (95.3
      96.1 %) and Chryseobacterium (94.2-95.9 %) in the family Flavobacteriaceae.
      Phylogenetic trees generated using several treeing algorithms based on 16S rRNA
      gene sequences showed that this Antarctic marine isolate formed a distinct
      phyletic line within the genus Sejongia. The DNA G+C content of the strain was
      35.0 mol% and the major respiratory quinone was MK-6. Several phenotypic and
      chemotaxonomic characteristics, including temperature and NaCl optima for growth,
      oxidase activity and the proportions of major cellular fatty acids, served to
      differentiate the strain from the recognized species of the genus Sejongia.
      Therefore strain IMCC3228(T) represents a novel species of the genus Sejongia,
      for which the name Sejongia marina sp. nov. is proposed. The type strain is
      IMCC3228(T) (=KCCM 42689(T)=NBRC 103143(T)).

PMID- 18048750
TI  - Ulvibacter antarcticus sp. nov., isolated from Antarctic coastal seawater.
AB  - A seawater bacterium, designated IMCC3101(T), was isolated from Antarctic coastal
      seawater. The strain was Gram-negative, chemoheterotrophic, obligately aerobic,
      pigmented dark yellow (flexirubin-type pigments) and devoid of gliding and
      flagellar motility. On the basis of 16S rRNA gene sequence comparisons, the most
      closely related species was Ulvibacter litoralis (96.6 %). Phylogenetic trees
      generated by using 16S rRNA gene sequences confirmed that the strain belonged to
      the genus Ulvibacter in the family Flavobacteriaceae. The DNA G+C content was
      37.0 mol% and the major respiratory quinone was MK-6. Several phenotypic
      characteristics, including cell and colony morphology, the absence of gliding
      motility and the temperature range for growth, serve to differentiate the strain
      from the only species in the genus Ulvibacter with a validly published name (U.
      litoralis). Therefore, strain IMCC3101(T) represents a novel species of the genus
      Ulvibacter, for which the name Ulvibacter antarcticus sp. nov. is proposed. The
      type strain is IMCC3101(T) (=KCCM 42686(T)=NBRC 102682(T)).

PMID- 18048751
TI  - Shewanella haliotis sp. nov., isolated from the gut microflora of abalone,
      Haliotis discus hannai.
AB  - A motile, rod-shaped, pink-orange pigmented bacterium, designated strain DW01(T),
      was isolated from the gut microflora of abalone collected from the South Sea
      (Republic of Korea). Cells were Gram-negative, facultatively anaerobic, catalase-
      and oxidase-positive. The major fatty acids were iso-C(15 : 0) (17.7 %), C(16 :
      0) (13.4 %), iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c (12.5 %) and C(17 :
      1)omega8c (10.7 %). The DNA G+C content was 53.7 mol%. A phylogenetic tree based
      on the 16S rRNA gene sequences showed that strain DW01(T) forms a lineage of the
      genus Shewanella and is closely related to Shewanella algae ATCC 51192(T) (98.3 %
      sequence similarity) and to other members of the genus Shewanella (91.0-94.9 %).
      The phenotypic characteristics and DNA-DNA hybridization relatedness data
      indicate that strain DW01(T) should be distinguished from S. algae ATCC 51192(T).
      On the basis of the data presented in this study, strain DW01(T) represents a
      novel species, for which the name Shewanella haliotis sp. nov. is proposed. The
      type strain is DW01(T) (=KCTC 12896(T)=JCM 14758(T)).

PMID- 18048752
TI  - Nocardia speluncae sp. nov., isolated from a cave.
AB  - The taxonomic status of a mycolic acid-containing actinomycete, isolated from a
      natural cave on Jeju Island, Republic of Korea, was investigated by means of a
      polyphasic approach. The isolate, designated strain N2-11(T), produced yellow- to
      orange-coloured vegetative hyphae and white- to pinkish white-coloured aerial
      mycelia, both of which fragmented into irregular rod-shaped elements.
      Phylogenetic analyses based on 16S rRNA gene sequences revealed that the organism
      belonged to the family Nocardiaceae, occupying a distinct position between
      Nocardia harenae and a Nocardia carnea cluster. The results of chemotaxonomic
      analyses were consistent with the affiliation of the organism with the genus
      Nocardia. On the basis of 16S rRNA gene sequence similarities, the closest
      phylogenetic neighbours were the type strains of N. carnea (98.3 %), Nocardia
      flavorosea (98.0 %), Nocardia sienata (97.9 %) and Nocardia testacea (97.8 %),
      but the organism could be clearly distinguished from its phylogenetic relatives
      with reference to a broad range of physiological markers. On the basis of
      phenotypic and molecular genetic data presented in this study, strain N2-11(T)
      represents a novel species of the genus Nocardia, for which the name Nocardia
      speluncae sp. nov. is proposed. The type strain is N2-11(T) (=JBRI 2006(T) =KCTC
      19223(T) =DSM 45078(T)).

PMID- 18048753
TI  - Prevotella maculosa sp. nov., isolated from the human oral cavity.
AB  - Three strains of anaerobic Gram-negative bacilli isolated from human oral sites
      were subjected to a comprehensive range of phenotypic and genotypic tests and
      were found to comprise a homogeneous group. 16S rRNA gene sequence analysis
      revealed the strains to constitute a novel group within the genus Prevotella,
      most closely related to Prevotella oris and Prevotella salivae. A novel species,
      Prevotella maculosa sp. nov., is proposed to accommodate these strains.
      Prevotella maculosa is saccharolytic and produces acetic and succinic acids as
      end products of fermentation. The G+C content of the DNA of the type strain is 48
      mol%. The type strain of Prevotella maculosa is W1609(T) (=DSM 19339(T) =CCUG
      54766(T)).

PMID- 18048755
TI  - Emended descriptions of the genus Lewinella and of Lewinella cohaerens, Lewinella
      nigricans and Lewinella persica, and description of Lewinella lutea sp. nov. and
      Lewinella marina sp. nov.
AB  - Two strains, MKG-38(T) and FYK2402M69(T), were isolated from a marine sediment
      sample and a sea snail, respectively, both collected on the Pacific coast of
      Japan. Phylogeny of these new isolates based on 16S rRNA gene sequences indicated
      that they are members of the genus Lewinella. Morphological, physiological and
      biochemical properties of these two isolates, together with the type strains of
      the three previously described species of the genus Lewinella, were
      characterized. The new isolates were Gram-negative, aerobic, rod-shaped, chemo
      organotrophic and able to degrade starch and CM-cellulose. A comparative
      polyphasic study showed that these two isolates represent two novel species of
      the genus Lewinella, for which the names Lewinella marina sp. nov. (type strain,
      MKG-38(T)=NBRC 102633(T)=NCIMB 14312(T)) and Lewinella lutea sp. nov. (type
      strain, FYK2402M69(T)=NBRC 102634(T)=NCIMB 14313(T)) are proposed. Emended
      descriptions of the genus Lewinella (Sly et al. 1998) and of Lewinella cohaerens,
      Lewinella nigricans and Lewinella persica are also proposed.

PMID- 18048754
TI  - Howardella ureilytica gen. nov., sp. nov., a Gram-positive, coccoid-shaped
      bacterium from a sheep rumen.
AB  - An unidentified obligately anaerobic, fastidious, Gram-positive, non-motile, non
      spore-forming, non-fermentative coccoid-shaped bacterium (designated strain GPC
      589(T)) was isolated from the rumen fluid of a sheep. The major fatty acid
      constituents (>5 %) were C(16 : 0) (29.2 %), C(18 : 0) (40.7 %) and an
      unidentified compound (19.7 %) with an equivalent chain-length of 13.523. The G+C
      content of the DNA was 34 mol%. The organism was strongly ureolytic and generated
      ATP through the hydrolysis of urea. Comparative 16S rRNA gene sequence analysis
      demonstrated that strain GPC 589(T) was far removed, phylogenetically, from the
      ruminococci and related Gram-positive anaerobic cocci but exhibited a
      phylogenetic association with Clostridium rRNA cluster XIVa [as defined by
      Collins, M. D., Lawson, P. A., Willems, A., Cordoba, J. J., Fernandez-Garayzabal,
      J., Garcia, P., Cai, J., Hippe, H. & Farrow, J. A. E. (1994). Int J Syst
      Bacteriol 44, 812-826]. Sequence divergence values of 12.5 % or more were
      observed between strain GPC 589(T) and all other recognized species within this
      and related rRNA clostridial clusters. Phylogenetic analysis showed that strain
      GPC 589(T) represents a new genus within cluster XIVa. On the basis of both
      phylogenetic and phenotypic evidence, it is proposed that strain GPC 589(T)
      should be classified as representing a new genus and novel species, Howardella
      ureilytica gen. nov., sp. nov. The type strain is strain GPC 589(T) (=DSM
      15118(T)=JCM 13267(T)).

PMID- 18048756
TI  - Leuconostoc holzapfelii sp. nov., isolated from Ethiopian coffee fermentation and
      assessment of sequence analysis of housekeeping genes for delineation of
      Leuconostoc species.
AB  - A Gram-positive, ovoid lactic acid bacterium, strain LMG 23990(T), was isolated
      from Ethiopian coffee fermentation. 16S rRNA gene sequence analysis indicated
      that the novel strain belongs to the genus Leuconostoc, with Leuconostoc citreum
      and Leuconostoc lactis as the closest neighbours (99.6 and 99.0 % 16S rRNA gene
      sequence similarity, respectively). Genotypic fingerprinting by fluorescent
      amplified fragment length polymorphism, whole-cell protein electrophoresis, DNA
      DNA hybridizations, comparative sequence analysis of pheS, rpoA, atpA, and
      physiological and biochemical tests allowed us to differentiate strain LMG
      23990(T) from all established Leuconostoc species. Strain LMG 23990(T) (=CCUG
      54536(T)) therefore represents a novel species, for which the name Leuconostoc
      holzapfelii sp. nov. is proposed.

PMID- 18048757
TI  - Nocardioides marinisabuli sp. nov., a novel actinobacterium isolated from beach
      sand.
AB  - The taxonomic position of a novel actinobacterium (designated SBS-12(T)), which
      was isolated from beach sand on Jeju Island, Republic of Korea, was determined
      following a polyphasic taxonomic characterization. Cells of the organism were
      Gram-positive, catalase-positive, oxidase-negative and non-motile rods. The
      organism contained ll-diaminopimelic acid in the cell-wall peptidoglycan and MK
      8(H(4)) as predominant menaquinone, and had a polar lipid profile containing
      phosphatidylglycerol and phosphatidylinositol, iso-C(16 : 0) as the major fatty
      acid and a DNA G+C content of 73.1 mol%. A neighbour-joining tree based on 16S
      rRNA gene sequences showed that the organism occupies a distinct phylogenetic
      position within the radiation including representatives of the family
      Nocardioidaceae. High levels of 16S rRNA gene sequence similarity were found with
      Nocardioides kribbensis (97.2 %), Nocardioides aquiterrae (96.9 %), Nocardioides
      pyridinolyticus (96.6 %) and Nocardioides aquaticus (96.3 %). The combination of
      morphological and chemotaxonomic characteristics was consistent with
      classification in the genus Nocardioides, but the isolate can be differentiated
      from all Nocardioides species with validly published names by a range of
      physiological properties. The name Nocardioides marinisabuli sp. nov. is proposed
      for this novel organism, with the type strain SBS-12(T) (=JBRI 2003(T)=KCCM
      42681(T)=DSM 18965(T)).

PMID- 18048758
TI  - Methermicoccus shengliensis gen. nov., sp. nov., a thermophilic, methylotrophic
      methanogen isolated from oil-production water, and proposal of Methermicoccaceae
      fam. nov.
AB  - A thermophilic, methylotrophic methanogen, strain ZC-1(T), was isolated from the
      Shengli oilfield, China. Cells of strain ZC-1(T) were motile cocci, 0.7-1.0
      microm in diameter and always occurred in clusters of two to four cells. Lysis
      susceptibility experiments and analysis of transmission electron micrographs of
      strain ZC-1(T) suggested the presence of a proteinaceous cell wall. Strain ZC
      1(T) used methanol, methylamine and trimethylamine as substrates for
      methanogenesis. Optimal growth, with a doubling time of around 5 h, occurred at
      pH 6.0-6.5, 65 degrees C, 0.3-0.5 M NaCl and 0.05-0.20 M MgCl(2). The DNA G+C
      content of this organism was 56 mol%. Analysis of 16S rRNA gene sequence and the
      inferred amino acid sequence of the mcrA gene of strain ZC-1(T) indicated that it
      is related specifically to members of the family Methanosaetaceae (90.6 and 76.6
      % sequence similarity, respectively). However, strain ZC-1(T) failed to grow with
      acetate as substrate for methanogenesis, which is a special characteristic of the
      family Methanosaetaceae. Based on these phenotypic and phylogenic
      characteristics, strain ZC-1(T) is proposed to represent a novel genus and
      species, for which the name Methermicoccus shengliensis gen. nov., sp. nov. is
      proposed. The type strain is ZC-1(T) (=CGMCC 1.5056(T)=DSM 18856(T)).
      Methermicoccaceae fam. nov. is also proposed.

PMID- 18048759
TI  - Candida flosculorum sp. nov. and Candida floris sp. nov., two yeast species
      associated with tropical flowers.
AB  - Two ascomycetous yeast species, Candida flosculorum sp. nov. and Candida floris
      sp. nov., were isolated from tropical flowers and their associated insects. C.
      flosculorum was isolated from flower bracts of Heliconia velloziana and Heliconia
      episcopalis (Heliconiaceae) collected from two Atlantic rain forest sites in
      Brazil. C. floris was isolated from flowers of Ipomoea sp. (Convolvulaceae)
      growing on the banks of the river Paraguai in the pantanal ecosystem in Brazil
      and from an adult of the stingless bee Trigona sp. and a flower of Merremia
      quinquefolia (Convolvulaceae) in Costa Rica. C. flosculorum belongs to the
      Metschnikowiaceae clade and C. floris belongs to the Starmerella clade. The type
      strain of C. flosculorum is UFMG-JL13(T) (=CBS 10566(T)=NRRL Y-48258(T)) and the
      type strain of C. floris is UWO(PS) 00-226.2(T) (=CBS 10593(T)=NRRL Y-48255(T)).

PMID- 18048761
TI  - Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion
      injury, preconditioning, and postconditioning.
AB  - Therapeutic strategies to protect the ischemic myocardium have been studied
      extensively. Reperfusion is the definitive treatment for acute coronary
      syndromes, especially acute myocardial infarction; however, reperfusion has the
      potential to exacerbate lethal tissue injury, a process termed "reperfusion
      injury." Ischemia/reperfusion injury may lead to myocardial infarction, cardiac
      arrhythmias, and contractile dysfunction. Ischemic preconditioning of myocardium
      is a well described adaptive response in which brief exposure to
      ischemia/reperfusion before sustained ischemia markedly enhances the ability of
      the heart to withstand a subsequent ischemic insult. Additionally, the
      application of brief repetitive episodes of ischemia/reperfusion at the immediate
      onset of reperfusion, which has been termed "postconditioning," reduces the
      extent of reperfusion injury. Ischemic pre- and postconditioning share some but
      not all parts of the proposed signal transduction cascade, including the
      activation of survival protein kinase pathways. Most experimental studies on
      cardioprotection have been undertaken in animal models, in which
      ischemia/reperfusion is imposed in the absence of other disease processes.
      However, ischemic heart disease in humans is a complex disorder caused by or
      associated with known cardiovascular risk factors including hypertension,
      hyperlipidemia, diabetes, insulin resistance, atherosclerosis, and heart failure;
      additionally, aging is an important modifying condition. In these diseases and
      aging, the pathological processes are associated with fundamental molecular
      alterations that can potentially affect the development of ischemia/reperfusion
      injury per se and responses to cardioprotective interventions. Among many other
      possible mechanisms, for example, in hyperlipidemia and diabetes, the
      pathological increase in reactive oxygen and nitrogen species and the use of the
      ATP-sensitive potassium channel inhibitor insulin secretagogue antidiabetic drugs
      and, in aging, the reduced expression of connexin-43 and signal transducer and
      activator of transcription 3 may disrupt major cytoprotective signaling pathways
      thereby significantly interfering with the cardioprotective effect of pre- and
      postconditioning. The aim of this review is to show the potential for developing
      cardioprotective drugs on the basis of endogenous cardioprotection by pre- and
      postconditioning (i.e., drug applied as trigger or to activate signaling pathways
      associated with endogenous cardioprotection) and to review the evidence that
      comorbidities and aging accompanying coronary disease modify responses to
      ischemia/reperfusion and the cardioprotection conferred by preconditioning and
      postconditioning. We emphasize the critical need for more detailed and
      mechanistic preclinical studies that examine car-dioprotection specifically in
      relation to complicating disease states. These are now essential to maximize the
      likelihood of successful development of rational approaches to therapeutic
      protection for the majority of patients with ischemic heart disease who are aged
      and/or have modifying comorbid conditions.

PMID- 18048762
TI  - Cytokines and beta-cell biology: from concept to clinical translation.
AB  - The tale of cytokines and the beta-cell is a long story, starting with in vitro
      discovery in 1984, evolving via descriptive and phenomenological studies to
      detailed mapping of the signalling pathways, gene- and protein expression
      patterns, molecular and biochemical effector mechanisms to in vivo studies in
      spontaneously diabetic and transgenic animal models. Only very recently have
      steps been taken to translate the accumulating compelling preclinical data into
      clinical trials. The aim of this chapter is to present an overview of early and
      recent key observations from our own groups as well as other laboratories that
      serve to illuminate the road from concept to clinical translation.

PMID- 18048764
TI  - The role for endoplasmic reticulum stress in diabetes mellitus.
AB  - Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a
      role in the pathogenesis of diabetes, contributing to pancreatic beta-cell loss
      and insulin resistance. Components of the unfolded protein response (UPR) play a
      dual role in beta-cells, acting as beneficial regulators under physiological
      conditions or as triggers of beta-cell dysfunction and apoptosis under situations
      of chronic stress. Novel findings suggest that "what makes a beta-cell a beta
      cell", i.e., its enormous capacity to synthesize and secrete insulin, is also its
      Achilles heel, rendering it vulnerable to chronic high glucose and fatty acid
      exposure, agents that contribute to beta-cell failure in type 2 diabetes. In this
      review, we address the transition from physiology to pathology, namely how and
      why the physiological UPR evolves to a proapoptotic ER stress response and which
      defenses are triggered by beta-cells against these challenges. ER stress may also
      link obesity and insulin resistance in type 2 diabetes. High fat feeding and
      obesity induce ER stress in liver, which suppresses insulin signaling via c-Jun N
      terminal kinase activation. In vitro data suggest that ER stress may also
      contribute to cytokine-induced beta-cell death. Thus, the cytokines IL-1beta and
      interferon-gamma, putative mediators of beta-cell loss in type 1 diabetes, induce
      severe ER stress through, respectively, NO-mediated depletion of ER calcium and
      inhibition of ER chaperones, thus hampering beta-cell defenses and amplifying the
      proapoptotic pathways. A better understanding of the pathways regulating ER
      stress in beta-cells may be instrumental for the design of novel therapies to
      prevent beta-cell loss in diabetes.

PMID- 18048765
TI  - Matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in serum
      do not reflect the analytes circulating in blood.

PMID- 18048763
TI  - Glucolipotoxicity: fuel excess and beta-cell dysfunction.
AB  - Glucotoxicity, lipotoxicity, and glucolipotoxicity are secondary phenomena that
      are proposed to play a role in all forms of type 2 diabetes. The underlying
      concept is that once the primary pathogenesis of diabetes is established,
      probably involving both genetic and environmental forces, hyperglycemia and very
      commonly hyperlipidemia ensue and thereafter exert additional damaging or toxic
      effects on the beta-cell. In addition to their contribution to the deterioration
      of beta-cell function after the onset of the disease, elevations of plasma fatty
      acid levels that often accompany insulin resistance may, as glucose levels begin
      to rise outside of the normal range, also play a pathogenic role in the early
      stages of the disease. Because hyperglycemia is a prerequisite for lipotoxicity
      to occur, the term glucolipotoxicity, rather than lipotoxicity, is more
      appropriate to describe deleterious effects of lipids on beta-cell function. In
      vitro and in vivo evidence supporting the concept of glucotoxicity is presented
      first, as well as a description of the underlying mechanisms with an emphasis on
      the role of oxidative stress. Second, we discuss the functional manifestations of
      glucolipotoxicity on insulin secretion, insulin gene expression, and beta-cell
      death, and the role of glucose in the mechanisms of glucolipotoxicity. Finally,
      we attempt to define the role of these phenomena in the natural history of beta
      cell compensation, decompensation, and failure during the course of type 2
      diabetes.

PMID- 18048766
TI  - Four SNPs on chromosome 9p21 in a South Korean population implicate a genetic
      locus that confers high cross-race risk for development of coronary artery
      disease.
AB  - OBJECTIVE: Recent genome-wide association studies have identified 4 SNPs on
      chromosome 9p21 associated with CAD (rs10757274 and rs2383206) and myocardial
      infarction (MI: rs2383207 and rs10757278) in White populations in Northern Europe
      and North America. We aimed to determine whether this locus confers significant
      susceptibility to CAD in a South Korean population, and thus cross-race
      susceptibility to CAD. METHODS AND RESULTS: We performed a case-control
      association study with 611 unrelated CAD patients and 294 normal controls from
      South Korea. Allelic associations of SNPs and SNP haplotypes with CAD were
      evaluated. Multivariate logistic regression analysis was used to adjust effects
      of clinical covariates. We found that 4 SNPs on chromosome 9p21 were associated
      with susceptibility to CAD in a South Korean population. The association remained
      significant after adjusting for significant clinical covariates (P=0.001 to
      0.024). We identified one risk haplotype (GGGG; P=0.017) and one protective
      haplotype (AAAA; P=0.007) for development of CAD. Further analysis suggested that
      the SNPs probably confer susceptibility to CAD in a dominance model (covariates
      adjusted P=0.001 to 0.024; OR=2.37 to 1.54). This represents the first study that
      expands association of these 9p21 SNPs with CAD beyond White populations.
      CONCLUSIONS: Chromosome 9p21 is an important susceptibility locus that confers
      high cross-race risk for development of CAD.

PMID- 18048767
TI  - Suppression of pro-inflammatory adhesion molecules by PPAR-delta in human
      vascular endothelial cells.
AB  - OBJECTIVE: Endothelial activation is implicated in atherogenesis and diabetes.
      The role of peroxisome proliferator-activated receptor-delta (PPAR-delta) in
      endothelial activation remains poorly understood. In this study, we investigated
      the anti-inflammatory effect of PPAR-delta and the mechanism involved. METHODS
      AND RESULTS: In human umbilical vein endothelial cells (HUVECs), the synthetic
      PPAR-delta ligands GW0742 and GW501516 significantly inhibited tumor necrosis
      factor (TNF)-alpha-induced expression of vascular cell adhesion molecule-1 and E
      selectin (assayed by real-time RT-PCR and Northern blotting), as well as the
      ensuing endothelial-leukocyte adhesion. Activation of PPAR-delta upregulated the
      expression of antioxidant genes superoxide dismutase 1, catalase, and thioredoxin
      and decreased reactive oxygen species production in ECs. Chromatin
      immunoprecipitation assays showed that GW0742 switched the association of BCL-6,
      a transcription repressor, from PPAR-delta to the vascular cell adhesion molecule
      (VCAM)-1 promoter. Small interfering RNA reduced endogenous PPAR-delta expression
      but potentiated the suppressive effect of GW0742 on EC activation, which suggests
      that the nonliganded PPAR-delta may have an opposite effect. CONCLUSIONS: We have
      demonstrated that ligand activation of PPAR-delta in ECs has a potent
      antiinflammatory effect, probably via a binary mechanism involving the induction
      of antioxidative genes and the release of nuclear corepressors. PPAR-delta
      agonists may have a potential for treating inflammatory diseases such as
      atherosclerosis and diabetes.

PMID- 18048768
TI  - CXCR3 antagonist NBI-74330 attenuates atherosclerotic plaque formation in LDL
      receptor-deficient mice.
AB  - OBJECTIVE: The chemokine receptor CXCR3 is implicated in migration of leukocytes
      to sites of inflammation. Antagonizing CXCR3 may be a strategy to inhibit
      inflammation-induced leukocyte migration and subsequently reduce atherosclerosis.
      We used the CXCR3 specific antagonist NBI-74330 to block CXCR3-mediated signaling
      in peritonitis and diet-induced atherosclerosis. METHODS AND RESULTS:
      Antagonizing CXCR3 with NBI-74330 resulted in a significant reduction in CD4+ T
      cell and macrophage migration to the peritoneal cavity, which was as shown in ex
      vivo migration studies totally CXCR3 dependent. Atherosclerotic lesion formation
      in the aortic valve leaflet area and the entire aorta was significantly inhibited
      in NBI-74330 treated mice. Lymph nodes draining from the aortic arch were
      significantly smaller in treated mice and were enriched in regulatory T cells and
      contained fewer activated T cells, whereas the markers for regulatory T cells
      within the lesion were enhanced after NBI-74330 treatment. CONCLUSIONS: This
      study shows for the first time that treatment with a CXCR3 antagonist results in
      attenuating atherosclerotic lesion formation by blocking direct migration of
      CXCR3+ effector cells from the circulation into the atherosclerotic plaque and by
      beneficially modulating the inflammatory response in the lesion and the lymph
      nodes draining from the atherosclerotic lesion.

PMID- 18048769
TI  - Divergent biophysical defects caused by mutant sodium channels in dilated
      cardiomyopathy with arrhythmia.
AB  - Mutations in SCN5A encoding the principal Na+ channel alpha-subunit expressed in
      human heart (Na(V)1.5) have recently been linked to an inherited form of dilated
      cardiomyopathy with atrial and ventricular arrhythmia. We compared the
      biophysical properties of 2 novel Na(V)1.5 mutations associated with this
      syndrome (D2/S4--R814W; D4/S3--D1595H) with the wild-type (WT) channel using
      heterologous expression in cultured tsA201 cells and whole-cell patch-clamp
      recording. Expression levels were similar among WT and mutant channels, and
      neither mutation affected persistent sodium current. R814W channels exhibited
      prominent and novel defects in the kinetics and voltage dependence of activation
      characterized by slower rise times and a hyperpolarized conductance-voltage
      relationship resulting in an increased "window current." This mutant also
      displayed enhanced slow inactivation and greater use-dependent reduction in peak
      current at fast pulsing frequencies. By contrast, D1595H channels exhibited
      impaired fast inactivation characterized by slower entry into the inactivated
      state and a hyperpolarized steady-state inactivation curve. Our findings
      illustrate the divergent biophysical defects caused by 2 different SCN5A
      mutations associated with familial dilated cardiomyopathy. Retrospective review
      of the published clinical data suggested that cardiomyopathy was not common in
      the family with D1595H, but rather sinus bradycardia was the predominant clinical
      finding. However, for R814W, we speculate that an increased window current
      coupled with enhanced slow inactivation and rate-dependent loss of channel
      availability provided a unique substrate predisposing myocytes to disordered Na+
      and Ca2+ homeostasis leading to myocardial dysfunction.

PMID- 18048770
TI  - Role of TRPM2 channel in mediating H2O2-induced Ca2+ entry and endothelial
      hyperpermeability.
AB  - Oxidative stress through the production of oxygen metabolites such as hydrogen
      peroxide (H2O2) increases vascular endothelial permeability. H2O2 stimulates ADP
      ribose formation, which in turn opens transient receptor potential melastatin
      (TRPM)2 channels. Here, in endothelial cells, we demonstrate transcript and
      protein expression of TRPM2, a Ca2+-permeable, nonselective cation channel. We
      further show the importance of TRPM2 expression in signaling of increased
      endothelial permeability by oxidative stress. Exposure of endothelial cell
      monolayers to sublytic concentrations of H2O2 induced a cationic current measured
      by patch-clamp recording and Ca2+ entry detected by intracellular fura-2
      fluorescence. H2O2 in a concentration-dependent manner also decreased trans
      monolayer transendothelial electrical resistance for 3 hours (with maximal effect
      seen at 300 micromol/L H2O2), indicating opening of interendothelial junctions.
      The cationic current, Ca2+ entry, and transendothelial electrical resistance
      decrease elicited by H2O2 were inhibited by siRNA depleting TRPM2 or antibody
      blocking of TRPM2. H2O2 responses were attenuated by overexpression of the
      dominant-negative splice variant of TRPM2 or inhibition of ADP-ribose formation.
      Overexpression of the full-length TRPM2 enhanced H2O2-mediated Ca2+ entry,
      cationic current, and the transendothelial electrical resistance decrease. Thus,
      TRPM2 mediates H2O2-induced increase in endothelial permeability through the
      activation of Ca2+ entry via TRPM2. TRPM2 represents a novel therapeutic target
      directed against oxidant-induced endothelial barrier disruption.

PMID- 18048771
TI  - Extracellular matrix metalloproteinase inducer (CD147) is a novel receptor on
      platelets, activates platelets, and augments nuclear factor kappaB-dependent
      inflammation in monocytes.
AB  - In atherosclerosis, circulating platelets interact with endothelial cells and
      monocytes, leading to cell activation and enhanced recruitment of leukocytes into
      the vascular wall. The invasion of monocytes is accompanied by overexpression of
      matrix metalloproteinases (MMPs), which are thought to promote atherosclerosis
      and trigger plaque rupture. Following interaction with itself, the extracellular
      matrix metalloproteinase inducer (EMMPRIN) induces MMP synthesis via a little
      known intracellular pathway. Recently, we showed upregulation of EMMPRIN on
      monocytes during acute myocardial infarction. EMMPRIN also stimulates secretion
      of MMP-9 by monocytes and of MMP-2 by smooth muscle cells, indicating that it may
      be an important regulator of MMP activity. Expression of EMMPRIN on platelets has
      not been described until now. Here, we demonstrate that resting platelets show
      low surface expression of EMMPRIN, which is upregulated by various platelet
      stimulators (flow cytometry). EMMPRIN is located in the open canalicular system
      and in alpha granules of platelets (according to electron microscopy and sucrose
      gradient ultracentrifugation). Platelet stimulation with recombinant EMMPRIN-Fc
      induced surface expression of CD40L and P-selectin (according to flow cytometry),
      suggesting that EMMPRIN-EMMPRIN interaction activates platelets. Coincubation of
      platelets with monocytes induced EMMPRIN-mediated nuclear factor kappaB
      activation (according to Western blot) in monocytes with increased MMP-9
      (zymography), interleukin-6, and tumor necrosis factor-alpha secretion (according
      to ELISA) by monocytes. In conclusion, EMMPRIN displays a new platelet receptor
      that is upregulated on activated platelets. Binding of EMMPRIN to platelets
      fosters platelet degranulation. Platelet-monocyte interactions via EMMPRIN
      stimulate nuclear factor kappaB-driven inflammatory pathways in monocytes, such
      as MMP and cytokine induction. Thus, EMMPRIN may represent a novel target to
      diminish the burden of protease activity and inflammation in atherosclerosis.

PMID- 18048772
TI  - The importance of external validity.

PMID- 18048773
TI  - Keeping the point-of-sale environment at the forefront.

PMID- 18048774
TI  - Another example of an illicit cigarette market: a study of psychiatric patients
      in Toronto, Ontario.

PMID- 18048775
TI  - Spinning for India's independence.

PMID- 18048776
TI  - The Bandoeng Conference of 1937: a milestone in health and development.

PMID- 18048777
TI  - HIV-associated orphanhood and children's psychosocial distress: theoretical
      framework tested with data from Zimbabwe.
AB  - OBJECTIVES: We measured the psychosocial effect of orphanhood in a sub-Saharan
      African population and evaluated a new framework for understanding the causes and
      consequences of psychosocial distress among orphans and other vulnerable
      children. METHODS: The framework was evaluated using data from 5321 children aged
      12 to 17 years who were interviewed in a 2004 national survey in Zimbabwe. We
      constructed a measure of psychosocial distress using principle components
      analysis. We used regression analyses to obtain standardized parameter estimates
      of psychosocial distress and odds ratios of early sexual activity. RESULTS:
      Orphans had more psychosocial distress than did nonorphans. For both genders,
      paternal, maternal, and double orphans exhibited more-severe distress than did
      nonorphaned, nonvulnerable children. Orphanhood remained associated with
      psychosocial distress after we controlled for differences in more-proximate
      determinants. Maternal and paternal orphans were significantly more likely than
      were nonorphaned, nonvulnerable children to have engaged in sexual activity.
      These differences were reduced after we controlled for psychosocial distress.
      CONCLUSIONS: Orphaned adolescents in Zimbabwe suffer greater psychosocial
      distress than do nonorphaned, nonvulnerable children, which may lead to increased
      likelihood of early onset of sexual intercourse and HIV infection. The effect of
      strategies to provide psychosocial support should be evaluated scientifically.

PMID- 18048778
TI  - Improvements in middle school student dietary intake after implementation of the
      Texas Public School Nutrition Policy.
AB  - OBJECTIVES: We assessed the effect of the Texas Public School Nutrition Policy on
      middle school student lunchtime food consumption. METHODS: Three years of lunch
      food records were collected from middle school students in southeast Texas:
      baseline (2001-2002), after local district changes (2002-2003), and 1 year after
      implementation of the Texas Public School Nutrition Policy (2005-2006). Students
      recorded amount and source of foods and beverages they consumed. Analysis of
      variance and covariance and nonparametric tests were used to compare intake after
      the policy change with intake during the 2 previous years. RESULTS: After
      implementation of the nutrition policy, student lunch consumption of vegetables,
      milk, and several nutrients increased (protein, fiber, vitamins A and C, calcium,
      and sodium), and consumption of less desirable items (sweetened beverages, snack
      chips) decreased, as did percentage of energy from fat. Most of the desired
      nutrients and foods (vegetables and milk) were obtained from the National School
      Lunch Program meal. Fewer sweetened beverages, candy, chips, and dessert foods
      were purchased and consumed, but more of these items were brought from home and
      purchased from the snack bar. CONCLUSIONS: Overall, state school nutrition
      policies can improve the healthfulness of foods consumed by students at lunch.

PMID- 18048780
TI  - Autonomy, paternalism, and justice: ethical priorities in public health.
AB  - With attention to the field of public health ethics growing, significant time has
      been devoted to identifying a sound ethical justification for paternalistic
      interventions that override individual autonomy to prevent people from adopting
      unhealthy behaviors. Efforts focused on specifying the conditions that warrant
      paternalism, however, are largely misplaced. On empirical and ethical grounds,
      public health should seek instead to expand individual autonomy to improve
      population health. To promote autonomy, the field should redirect current efforts
      toward clarifying principles of justice. Although public health's most highly
      visible stance is associated with an egalitarian conception of "social justice,"
      it is imperative that public health professionals address gaping divisions in
      public understandings of justice. I present recommendations for initiating this
      process.

PMID- 18048779
TI  - Cardiovascular disease and global health equity: lessons from tuberculosis
      control then and now.
AB  - Early 20th-century cardiovascular voluntary organizations in the United States
      drew strength from the well-established antituberculosis movement. By mid
      century, heart disease among the young and tuberculosis had declined in this
      country. The international fight against tuberculosis has gathered force since
      the 1990s. Meanwhile, support for international cardiovascular interventions has
      lagged behind. We trace the divergent path of the international cardiovascular
      movement and suggest ways in which it could once again learn from the trials and
      achievements of tuberculosis control.

PMID- 18048781
TI  - The health of trafficked women: a survey of women entering posttrafficking
      services in Europe.
AB  - Trained counselors interviewed 192 women who had been trafficked and sexually
      exploited about abuse and evaluated their physical and mental health status
      within 14 days of entry into posttrafficking services. Most reported physical or
      sexual violence while trafficked (95%), pre-trafficking abuse (59%), and multiple
      posttrafficking physical and psychological problems. Newly identified trafficked
      women require immediate attention to address posttrauma symptoms and adequate
      recovery time before making decisions about participating in prosecutorial or
      immigration proceedings or returning home.

PMID- 18048782
TI  - Maternal depressive symptoms, parenting self-efficacy, and child growth.
AB  - OBJECTIVES: We assessed whether maternal depressive symptoms and parenting self
      efficacy were associated with child growth delay. METHODS: We collected data from
      a random sample of 595 low-income mothers and their children aged 6 to 24 months
      in Teresina, Piaui, Brazil, including information on sociodemographic
      characteristics, mothers' depressive symptoms and parenting self-efficacy, and
      children's anthropometric characteristics. We used adjusted logistic regression
      models in our analyses. RESULTS: Depressive symptoms among mothers were
      associated with 1.8 times higher odds (95% confidence interval [CI] = 1.1, 2.9)
      of short stature among children. Parenting self-efficacy was not associated with
      short stature, nor did it mediate or modify the relationship between depressive
      symptoms and short stature. Maternal depressive symptoms and self-efficacy were
      not related to child underweight. CONCLUSIONS: Our results showed that among low
      income Brazilian families maternal depressive symptoms, but not self-efficacy,
      were associated with short stature in children aged 6 to 24 months after
      adjustment for known predictors of growth.

PMID- 18048783
TI  - Racial/ethnic minority children's use of psychiatric emergency care in
      California's Public Mental Health System.
AB  - OBJECTIVES: We examined rates and intensity of crisis services use by
      race/ethnicity for 351,174 children younger than 18 years who received specialty
      mental health care from California's 57 county public mental health systems
      between July 1998 and June 2001. METHODS: We used fixed-effects regression for a
      controlled assessment of racial/ethnic disparities in children's use of hospital
      based services for the most serious mental health crises (crisis stabilization
      services) and community-based services for other crises (crisis intervention
      services). RESULTS: African American children were more likely than were White
      children to use both kinds of crisis care and made more visits to hospital-based
      crisis stabilization services after initial use. Asian American/Pacific Islander
      and American Indian/Alaska Native children were more likely than were White
      children to use hospital-based crisis stabilization services but, along with
      Latino children, made fewer hospital-based crisis stabilization visits after an
      initial visit. CONCLUSIONS: African American children used both kinds of crisis
      services more than did White children, and Asian Americans/Pacific Islander and
      American Indians/Alaska Native children visited only when they experienced the
      most disruptive and troubling kind of crises, and made nonrecurring visits.

PMID- 18048784
TI  - Epidemiological characterization of individuals with newly reported HIV
      infection: South Carolina, 2004-2005.
AB  - OBJECTIVES: We used statewide data to assess HIV disease stage at initial
      diagnosis and laboratory indications for initiating antiretroviral therapy among
      South Carolina residents with newly diagnosed HIV infection. METHODS: Initial
      CD4+ counts and viral loads among individuals diagnosed with HIV between May 2004
      and April 2005 were categorized according to current staging and treatment
      guidelines. RESULTS: Of 759 individuals who had a CD4+ count reported, 34% and
      56% had counts of 200 cells/mm(3) or below and 350 cells/mm(3) or below,
      respectively. CD4+ counts of 200 cells/mm(3) or below were significantly
      associated with male gender (adjusted odds ratio [AOR] = 2.07; 95% confidence
      interval [CI] = 1.36, 3.16), age above 29 years (AOR = 2.45; 95% CI = 1.51,
      3.96), and hospital-reported patients (AOR = 2.17; 95% CI = 1.41, 3.36). The same
      characteristics were significant risk factors for elevated viral loads.
      CONCLUSIONS: At least in South Carolina, HIV diagnoses are delayed in a
      significant percentage of patients. New testing strategies need to be implemented
      to encourage earlier HIV diagnoses, and future studies should evaluate the
      effects of expanded routine testing on earlier detection.

PMID- 18048785
TI  - Equity of skilled birth attendant utilization in developing countries: financing
      and policy determinants.
AB  - OBJECTIVES: Developing countries with higher health care spending have greater
      overall utilization of maternal health services than do countries with lower
      spending. However, the rich tend to disproportionately use these services. We
      assessed whether redistributive government policies in the context of higher
      levels of health spending were associated with more-equitable use of skilled
      birth attendants (doctors, nurses, or midwives) between rich and poor. METHODS:
      We used data from Demographic and Health Surveys of 45 developing countries and
      disaggregated by wealth quintile. Multivariable regression analyses were used to
      assess the joint effect of higher health care expenditures, the wealth
      distribution of women's fifth-grade education (a proxy for redistributive policy
      environment within the central government) and the overall proportion of women
      with fifth-grade education (a proxy for female literacy and an indicator of
      governments' commitment to girls' education). RESULTS: We found that utilization
      of skilled birth attendants was more equitable when higher health expenditures
      were accompanied by redistributive education policies. CONCLUSIONS: Higher health
      care expenditures should be accompanied by redistributive policies to reduce the
      gap in utilization of skilled birth attendants between poorer and richer women in
      developing countries.

PMID- 18048786
TI  - Understanding dog owners' increased levels of physical activity: results from
      RESIDE.
AB  - We examined the influence of dog ownership on physical activity, independent of
      demographic, intrapersonal, and perceived environmental factors, in a cross
      sectional survey of 1813 adults. Although only 23% of the dog owners walked their
      dogs 5 or more times per week, the adjusted odds of achieving sufficient physical
      activity and walking were 57% to 77% higher among dog owners compared with those
      not owning dogs (P< .05). Dog ownership was independently associated with
      physical activity and walking. Actively encouraging more dog walking may increase
      community physical activity levels.

PMID- 18048787
TI  - Immigration and generational trends in body mass index and obesity in the United
      States: results of the National Latino and Asian American Survey, 2002-2003.
AB  - OBJECTIVES: We examined patterns of body mass index (BMI) and obesity among a
      nationally representative sample of first-, second-, and third-generation Latinos
      and Asian Americans to reveal associations with nativity or country of origin.
      METHODS: We used data from the National Latino and Asian American Survey (2002
      2003) to generate nationally representative estimates of mean BMI and obesity
      prevalence and explored changes in the distribution of BMI by generational
      status. Analyses tested the association between generational status and BMI and
      examined whether this association varied by ethnicity, education, or gender.
      RESULTS: We found substantial heterogeneity in BMI and obesity by country of
      origin and an increase in BMI in later generations among most subgroups. The data
      suggest different patterns for Latinos and Asian Americans in the nature and
      degree of distributional changes in BMI with generational status in the United
      States. CONCLUSIONS: Generational status is associated with increased BMI and
      obesity among Latinos and Asian Americans. Aggregate estimates not accounting for
      nativity and country of origin may mask significant heterogeneity in the
      prevalence of obesity and patterns of distributional change, with implications
      for prevention strategies.

PMID- 18048788
TI  - Breastfeeding duration and childhood overweight among low-income children in
      Kansas, 1998-2002.
AB  - OBJECTIVES: We sought to determine whether increased duration of breast-feeding
      was associated with decreased risk of overweight among 4-year-old children in
      Kansas families with limited means. METHODS: We linked data on Kansas families
      from the Pediatric Nutrition Surveillance System and Pregnancy Nutrition
      Surveillance System, 1998 to 2002, to determine breastfeeding duration and weight
      status at age 4 years. Overweight among 4-year-old children was defined as body
      mass index-for-age at the 95th percentile and above. Linked analysis included
      3692 children. Logistic regression was applied to determine odds of being
      overweight at each duration of breastfeeding. RESULTS: Breastfeeding duration
      considered independently showed a significant protective association with
      childhood overweight at age 4 years for all non-Hispanics (odds ratio [OR]=0.72;
      95% confidence interval [CI]=0.55, 0.94) and for Whites only (OR=0.68; CI=0.50,
      0.92). When we controlled for other significant risk factors for childhood
      overweight, the association diminished and was not statistically significant.
      CONCLUSIONS: Although breastfeeding for longer duration appeared to be protective
      against overweight among 4-year-old non-Hispanic children, cultural and
      environmental factors may override this protective benefit.

PMID- 18048789
TI  - Community health workers: social justice and policy advocates for community
      health and well-being.
AB  - Community health workers are resources to their communities and to the advocacy
      and policy world on several levels. Community health workers can connect people
      to health care and collect information relevant to policy. They are natural
      researchers who, as a result of direct interaction with the populations they
      serve, can recount the realities of exclusion and propose remedies for it. As
      natural researchers, they contribute to best practices while informing public
      policy with the information they can share. In this light, community health
      workers may also be advocates for social justice.

PMID- 18048790
TI  - Results of the 2004 National Worksite Health Promotion Survey.
AB  - OBJECTIVES: We examined worksite health promotion programs, policies, and
      services to monitor the achievement of the Healthy People 2010 worksite-related
      goal of 75% of worksites offering a comprehensive worksite health promotion
      program. METHODS: We conducted a nationally representative, cross-sectional
      telephone survey of worksite health promotion programs stratified by worksite
      size and industry type. Techniques appropriate for analyzing complex surveys were
      used to compute point estimates, confidence intervals, and multivariate
      statistics. RESULTS: Worksites with more than 750 employees consistently offered
      more programs, policies, and services than did smaller worksites. Only 6.9% of
      responding worksites offered a comprehensive worksite health promotion program.
      Sites with a staff person dedicated to and responsible for health promotion were
      significantly more likely to offer a comprehensive program, and sites in the
      agriculture and mining or financial services sector were significantly less
      likely than those in other industry sectors to offer such a program. CONCLUSIONS:
      Increasing the number, quality, and types of health promotion programs at
      worksites, especially smaller worksites, remains an important public health goal.

PMID- 18048791
TI  - The healthy migrant effect: new findings from the Mexican Family Life Survey.
AB  - OBJECTIVES: We used nationally representative longitudinal data from the Mexican
      Family Life Survey to determine whether recent migrants from Mexico to the United
      States are healthier than other Mexicans. Previous research has provided little
      scientific evidence that tests the "healthy migrant" hypothesis. METHODS:
      Estimates were derived from logistic regressions of whether respondents moved to
      the United States between surveys in 2002 and 2005, by gender and urban versus
      rural residence. Covariates included physical health measurements, self-reported
      health, and education measured in 2002. Our primary sample comprised 6446
      respondents aged 15 to 29 years. RESULTS: Health significantly predicted
      subsequent migration among females and rural males. However, the associations
      were weak, few health indicators were statistically significant, and there was
      substantial variation in the estimates between males and females and between
      urban and rural dwellers. CONCLUSIONS: On the basis of recent data for Mexico,
      the largest source of migrants to the United States, we found generally weak
      support for the healthy migrant hypothesis.

PMID- 18048792
TI  - Social and emotional consequences of refraining from sexual activity among
      sexually experienced and inexperienced youths in California.
AB  - OBJECTIVES: We examined the social and emotional consequences among adolescents
      of refraining from sexual activity (oral or vaginal sex) and whether these
      consequences differed over time and by gender and sexual experience. METHODS:
      Adolescents (N=612; 58% female) recruited from 2 schools were assessed at 4 time
      points separated by 6-month intervals, beginning in fall of ninth grade. RESULTS:
      The percentage of adolescents who reported only positive consequences (e.g., they
      felt responsible, friends were proud) dramatically decreased over time, whereas
      the percentage that reported negative consequences (e.g., they felt left out,
      partners became angry) steadily increased. Adolescent girls and sexually
      experienced adolescents were more likely to report both positive and negative
      consequences than were adolescent boys and sexually inexperienced adolescents.
      Adolescents who began the study with sexual experience were more likely to report
      positive consequences of refraining from sexual activity by the end of the study
      than those who initiated sexual activity later. CONCLUSIONS: Sexual education
      programs should address how adolescents can cope with or prevent negative
      consequences of refraining from sexual activity, so that decisions to abstain are
      rewarding and decisions to engage in sexual activity are motivated by maturity
      and readiness.

PMID- 18048793
TI  - Long-term health correlates of timing of sexual debut: results from a national US
      study.
AB  - OBJECTIVES: We explored long-term health consequences of age at sexual initiation
      and of abstinence until marriage to evaluate empirical support for the claim that
      postponing sexual initiation has beneficial health effects. METHODS: We analyzed
      data from the 1996 National Sexual Health Survey, a cross-sectional study of the
      US adult population. We compared sexual health outcomes among individuals who had
      initiated sexual activity at an early or late age versus a normative age. We also
      compared individuals whose first sexual intercourse had occurred before versus
      after marriage. RESULTS: Early initiation of sexual intercourse was associated
      with various sexual risk factors, including increased numbers of sexual partners
      and recent sexual intercourse under the influence of alcohol, whereas late
      initiation was associated with fewer risk factors. However, both early and late
      initiation were associated with sexual problems such as problems with arousal and
      orgasm, primarily among men. Relationship solidity and sexual relationship
      satisfaction were not associated with early or late initiation. CONCLUSIONS:
      Early sexual debut is associated with certain long-term negative sexual health
      outcomes, including increased sexual risk behaviors and problems in sexual
      functioning. Late initiation was also associated with sexual problems, especially
      among men. Further research is needed to understand how sexual initiation
      patterns affect later health outcomes.

PMID- 18048794
TI  - Injuries among US children with different types of disabilities.
AB  - OBJECTIVES: We sought to determine whether risk of injury differs among children
      on the basis of the type of disability, and whether the characteristics of injury
      episodes differ by disability status. METHODS: We used nationally representative
      data from the 1997-2005 National Health Interview Survey to compare medically
      attended injuries among children aged 0 to 17 years who had and did not have a
      disability. Characteristics of injury episodes were compared by disability
      status. We calculated prevalence and risk of injury by type of disability.
      RESULTS: Children who had a single disability had a significantly higher
      prevalence of injury than children without a disability (3.8% vs 2.5%; P<.01).
      Characteristics of injury episodes did not differ significantly by disability
      status (P>.05). After we controlled for sociodemographic variables, we found that
      only children with emotional or behavioral problems had a significantly higher
      risk of injury compared with children without a disability (prevalence
      ratio=1.50; 95% confidence interval=1.15, 1.97; P<.01). CONCLUSIONS: Children
      with certain types of disabilities are at a significantly higher risk of injuries
      than are children without disabilities, but the characteristics of injuries are
      similar.

PMID- 18048795
TI  - Leisure-time physical activity disparities among Hispanic subgroups in the United
      States.
AB  - Studies of leisure-time physical activity disparities for Hispanic individuals
      have not adjusted for sociodemographic confounds or accounted for variation by
      country of origin. We used the National Health Interview Survey to compare
      leisure-time physical activity among Hispanic and non-Hispanic White persons. All
      Hispanic subgroups were less active than were non-Hispanic White people, yet
      significant heterogeneity existed among Hispanic persons. Sociodemographic
      factors partly accounted for disparities among men; disparities among women
      persisted despite multivariate adjustments. Interventions must attend to these
      under-served yet varied sub-communities.

PMID- 18048796
TI  - Self-reported tuberculosis disease and tuberculin skin testing in the New York
      City House Ballroom community.
AB  - OBJECTIVES: We sought to describe the history of tuberculosis disease and
      tuberculin skin testing among the New York City House Ballroom community--a
      social network of diverse sexual and gender identities or expressions. METHODS:
      Members of the House Ballroom community were convenience sampled, surveyed, and
      tested for HIV in 2004. We identified characteristics associated with history of
      tuberculosis, tuberculin skin testing, and test positivity and described the
      timing of skin testing. RESULTS: Of 504 participants, 1.4% (n=7) reported a
      history of tuberculosis and 81.1% (n=404 of 498) had received a tuberculin skin
      test. Of those tested, 16 (4%) had positive results, which indicated latent
      infection, and 68% had received a test in the 2 years prior to the survey.
      Participants with health insurance were more likely and those with little
      education were less likely to have received a skin test. HIV-infected
      participants (16%) were not more likely to have received a tuberculin skin test
      compared with non-HIV-infected individuals. Foreign-born participants and self
      identified heterosexuals and bisexuals were more likely to have had positive skin
      tests. CONCLUSIONS: Self-reported history of tuberculosis was high among the
      House Ballroom community. Although many community members had a recent skin test,
      further efforts should target services to those who are HIV infected, have low
      education, lack health insurance, or are foreign born.

PMID- 18048797
TI  - Trends and disparities among diabetes-complicated births in Minnesota, 1993-2003.
AB  - We used Minnesota birth certificate data from 1993-2003 to test 2 hypotheses:
      rates of diabetes-complicated pregnancy are increasing, and disparities between
      more and less socially advantaged groups are widening. Significant increases
      occurred in rates (per 1000 live births) of prepregnancy and gestational diabetes
      mellitus (from 2.6 to 4.9 and 25.6 to 34.8, respectively). Increases were
      significant in all demographic groups except gestational diabetes among American
      Indian mothers, and disparities worsened among all groups. Targeted interventions
      and surveillance improvements are needed.

PMID- 18048798
TI  - Use of a population-based survey to describe the health of Boston public housing
      residents.
AB  - OBJECTIVES: We compared the health of public housing residents with other Boston
      residents through a random-digit-dial survey. METHODS: We used data from the
      Boston Behavioral Risk Factor Surveillance System collected in 2001 and 2003 to
      make crude and demographically adjusted comparisons between public housing
      residents and other city residents on measures of health status, access and
      utilization, and health behaviors. RESULTS: Public housing residents were more
      likely to report fair or poor overall health status, ever-diagnosed hypertension,
      current asthma, ever-diagnosed diabetes, obesity, disability, loss of 6 or more
      teeth, and feelings of depression for 15 days or more in the past month. Public
      housing residents were slightly more likely than others to be without health
      insurance or report financial barriers to medical care. Public housing residents
      reported more smoking and physical inactivity, less past-month binge drinking and
      past-year marijuana use, and similar levels of lifetime drug use. CONCLUSIONS:
      Public housing residents reported substantially poorer health than did other city
      residents across a variety of conditions but similar levels of access to and
      utilization of health care. Public health departments may be able to use
      established surveys to measure health among public housing residents.

PMID- 18048799
TI  - Differences in cardiovascular disease mortality associated with body mass between
      Black and White persons.
AB  - We analyzed cardiovascular disease mortality risks associated with obesity using
      participant-level meta-analysis of data from the Black Pooling Project for Black
      and White individuals. The adjusted relative risks (ARRs) were stronger among
      White participants than among Black participants for coronary heart disease
      AAR=1.21 (95% confidence interval [CI]=1.07, 1.36) versus 0.87 (95% CI=0.69,
      1.09), respectively, and cardiovascular disease ARR=1.18 (95% CI=1.07, 1.29)
      versus 0.91 (95% CI=0.77, 1.05), respectively. The results suggest that obesity
      is an independent risk factor in White people, and additional study of body size
      and disease progression is necessary in the assessment of racial disparities.

PMID- 18048800
TI  - Indigenous ways of knowing: implications for participatory research and
      community.
AB  - Researchers have a responsibility to cause no harm, but research has been a
      source of distress for indigenous people because of inappropriate methods and
      practices. The way researchers acquire knowledge in indigenous communities may be
      as critical for eliminating health disparities as the actual knowledge that is
      gained about a particular health problem. Researchers working with indigenous
      communities must continue to resolve conflict between the values of the academic
      setting and those of the community. It is important to consider the ways of
      knowing that exist in indigenous communities when developing research methods.
      Challenges to research partnerships include how to distribute the benefits of the
      research findings when academic or external needs contrast with the need to
      protect indigenous knowledge.

PMID- 18048801
TI  - Immigration and risk of childhood lead poisoning: findings from a case control
      study of New York City children.
AB  - OBJECTIVES: We investigated whether foreign birthplace and residence were
      associated with an increased risk of childhood lead poisoning. METHODS: We
      conducted a matched case-control study among New York City children (mean age=3
      years) tested for lead poisoning in 2002 (n=203 pairs). Children were matched on
      age, date of test, and residential area. Blood lead and housing data were
      supplemented by a telephone survey administered to parents or guardians.
      Conditional logistic regression analysis was used to examine the relationship of
      lead poisoning status to foreign birthplace and time elapsed since most recent
      foreign residence after adjustment for housing and behavioral risk factors.
      RESULTS: Both foreign birthplace and time since most recent foreign residence had
      strong adjusted associations with lead poisoning status, with children who had
      lived in a foreign country less than 6 months before their blood test showing a
      particularly elevated risk of lead poisoning relative to US-born children with no
      foreign residential history before their blood test (odds ratio [OR]=10.9; 95%
      confidence interval [CI]=3.3, 36.5). CONCLUSIONS: Our findings demonstrate an
      increased risk of lead poisoning among immigrant children.

PMID- 18048802
TI  - A participatory action research pilot study of urban health disparities using
      rapid assessment response and evaluation.
AB  - Healthy People 2010 made it a priority to eliminate health disparities. We used a
      rapid assessment response and evaluation (RARE) to launch a program of
      participatory action research focused on health disparities in an urban,
      disadvantaged Black community serviced by a major south Florida health center. We
      formed partnerships with community members, identified local health disparities,
      and guided interventions targeting health disparities. We describe the RARE
      structure used to triangulate data sources and guide intervention plans as well
      as findings and conclusions drawn from scientific literature and epidemiological,
      historic, planning, clinical, and ethnographic data. Disenfranchisement and
      socioeconomic deprivation emerged as the principal determinants of local health
      disparities and the most appropriate targets for intervention.

PMID- 18048803
TI  - Effect of a targeted subsidy on intake of fruits and vegetables among low-income
      women in the Special Supplemental Nutrition Program for Women, Infants, and
      Children.
AB  - OBJECTIVES: Intake of fruits and vegetables protects against several common
      chronic diseases, and low income is associated with lower intake. We tested the
      effectiveness of a subsidy for fruits and vegetables to the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC). METHODS: Women who
      enrolled for postpartum services (n=602) at 3 WIC sites in Los Angeles were
      assigned to an intervention (farmers' market or supermarket, both with redeemable
      food vouchers) or control condition (a minimal nonfood incentive). Interventions
      were carried out for 6 months, and participants' diets were followed for an
      additional 6 months. RESULTS: Intervention participants increased their
      consumption of fruits and vegetables and sustained the increase 6 months after
      the intervention was terminated (model adjusted R(2)=.13, P<.001). Farmers'
      market participants showed an increase of 1.4 servings per 4186 kJ (1000 kcal) of
      consumed food (P<.001) from baseline to the end of intervention compared with
      controls, and supermarket participants showed an increase of 0.8 servings per
      4186 kJ (P=.02). CONCLUSIONS: Participants valued fresh fruits and vegetables,
      and adding them to the WIC food packages will result in increased fruit and
      vegetable consumption.

PMID- 18048804
TI  - Acrolein induces heme oxygenase-1 through PKC-delta and PI3K in human bronchial
      epithelial cells.
AB  - Heme oxygenase-1 (HO-1) catalyzes the rate limiting reaction of heme metabolism
      and plays critical roles in resistance to oxidative stress and other cellular
      functions. It is well known that HO-1 is induced in response to various stresses;
      however, the signaling pathways involved remain incompletely elucidated. Acrolein
      is an alpha,beta-unsaturated aldehyde present in cigarette smoke and also a
      product of lipid peroxidation. In this investigation we studied HO-1 induction in
      response to acrolein and determined the signaling pathways involved in human
      bronchial epithelial cells (HBE1 cells). We demonstrated that acrolein
      significantly increased the HO-1 mRNA content and promoter activity. Acrolein
      mediated HO-1 induction was significantly attenuated by pan-protein kinase C
      (PKC) inhibitors RO318220, staurosporine, and PKC-delta selective inhibitor
      rottlerin and PKC-delta small interfering RNA. The HO-1 induction was also
      decreased by phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 and
      wortmannin. No significant effects on HO-1 induction were observed with the
      pretreatment of mitogen-activated protein kinase pathway inhibitors PD98059
      (ERK), SB203580 (p38MAPK) and JNKi, and conventional and atypical PKC inhibitors.
      Furthermore, Nrf2 silencing significantly attenuated the HO-1 induction by
      acrolein. Inhibition of PKC-delta significantly decreased acrolein-mediated Nrf2
      nuclear translocation, though inhibition of PI3K had no effect. Taken together,
      our results indicate that acrolein up-regulates HO-1 expression through both PKC
      delta and PI3K pathways in HBE1 cells; PKC-delta appears to regulate HO-1
      induction via modulating Nrf2 nuclear translocation, while PI3K may work through
      targeting on downstream signaling molecules other than Nrf2.

PMID- 18048805
TI  - Pulmonary microvascular endothelial cells form a tighter monolayer when grown in
      chronic hypoxia.
AB  - Unique among the vascular beds, loss of endothelial integrity in the pulmonary
      microcirculation due to injury can lead to rapidly fatal hypoxemia. The ability
      to regain confluence and re-establish barrier function is central to restoring
      proper gas exchange. The adult respiratory distress syndrome (ARDS) is a
      heterogeneous disease, however, meaning that endothelial cells within different
      regions of the lung do not likely see the same oxygen tension as they attempt to
      proliferate and re-establish an intact endothelial monolayer; the effect of
      hypoxia on the integrity of this newly formed endothelial monolayer is not clear.
      Immortalized human pulmonary microvascular endothelial cells (PMVEC) (ST1.6R
      cells) were sparsely plated and grown to confluence over 4 days in either
      normoxia (21% oxygen) or hypoxia (5% oxygen). Confluence attained in a hypoxic
      environment resulted in a tighter, less permeable endothelial monolayer (as
      determined by an increase in transendothelial electrical resistance, decreased
      permeability to fluorescently labeled macromolecules, and decreased hydraulic
      conductance). PMVEC grown to confluence under hypoxia had decreased RhoA
      activity; consistent with this finding, inhibition of Rho kinase, a well
      described downstream target of RhoA, markedly increased electrical resistance in
      normoxic, but not hypoxic, PMVEC. These results were confirmed in primary human
      and rat PMVEC. These data suggest that PMVEC grown to confluence under hypoxia
      form a tighter monolayer than similar cells grown under normoxia. This tighter
      barrier appears to be due, in part, to the inhibition of RhoA activity in hypoxic
      cells.

PMID- 18048806
TI  - Underreporting exacerbation of chronic obstructive pulmonary disease in a
      longitudinal cohort.
AB  - RATIONALE: Unreported exacerbations and failure to seek medical attention may
      have consequences on the health of patients with chronic obstructive pulmonary
      disease. OBJECTIVES: This study aims to determine the incidence of reported and
      unreported exacerbations, to identify predictors of reporting, and to compare the
      impact of reported and unreported exacerbations on health status. METHODS: The
      study is based on a multicenter Canadian cohort of patients with chronic
      obstructive pulmonary disease. MEASUREMENTS AND MAIN RESULTS: Patients completed
      a daily diary from which exacerbations were defined as a worsening of at least
      one key symptom (dyspnea, sputum amount, sputum color) recorded on at least 2
      consecutive days. Patients were asked to contact the study center if there was a
      sustained worsening of symptom. Reported exacerbations were events that led to
      contacting study center or health care visit. The study enrolled 421 patients.
      The overall incidence of diary exacerbations was 2.7 per person per year, but
      only 0.8 per person per year was reported. Predictors of reporting included age
      (HR [hazard ratio], 0.90; 95% confidence interval [CI], 0.81-0.98 per 5-yr
      increase), FEV(1)% predicted (HR, 0.84; 95% CI, 0.70-0.99 per 10% increase),
      number of symptoms at onset (HR, 1.59; 95% CI, 1.37-1.84 per additional symptom),
      and time of the week (HR, 0.35; 95% CI, 0.22-0.56 weekend vs. weekday). There was
      a clinically important decline in health status for 52% of patients with reported
      exacerbation and 43% with unreported exacerbations. CONCLUSIONS: This study has
      shown that less than one-third of the exacerbations were reported. The number of
      symptoms at onset was the most important predictor of reporting an exacerbation,
      and both reported and unreported exacerbations had an impact on health status.

PMID- 18048807
TI  - Extrapulmonary effects of chronic obstructive pulmonary disease on physical
      activity: a cross-sectional study.
AB  - RATIONALE: Physical activity is reduced in patients with chronic obstructive
      pulmonary disease (COPD). COPD has a systemic component that includes significant
      extrapulmonary effects that may contribute to its severity in individual
      patients. OBJECTIVES: To investigate the association of extrapulmonary effects of
      the disease and its comorbidities with reduced physical activity in patients with
      COPD. METHODS: In a cross-sectional study, 170 outpatients with COPD (GOLD
      [Global Initiative for Chronic Obstructive Lung Disease] stages I-IV; BODE [body
      mass index, airway obstruction, dyspnea, and exercise capacity] score 0-10)
      underwent a series of tests. Physical activity was assessed over 5 to 6
      consecutive days by using a multisensor accelerometer armband that records steps
      per day and the physical activity level (total daily energy expenditure divided
      by whole-night sleeping energy expenditure). Cardiovascular status was assessed
      by echocardiography, vascular Doppler sonography, and levels of N-terminal pro-B
      type natriuretic peptide. Mental status, metabolic/muscular status, systemic
      inflammation, and anemia were assessed by Beck Depression Inventory,
      bioelectrical impedance analysis, handgrip strength, high-sensitivity C-reactive
      protein/fibrinogen, and hemoglobin, respectively. MEASUREMENTS AND MAIN RESULTS:
      In a multivariate linear regression analysis using either steps per day or
      physical activity level as a dependent variable, the extrapulmonary parameters
      that were associated with reduced physical activity in patients with COPD
      independently of GOLD stages or BODE score were N-terminal pro-B-type natriuretic
      peptide levels, echocardiographically measured left ventricular diastolic
      function, and systemic inflammation. CONCLUSIONS: Higher values of systemic
      inflammation and left cardiac dysfunction are associated with reduced physical
      activity in patients with COPD.

PMID- 18048808
TI  - Relief of dyspnea involves a characteristic brain activation and a specific
      quality of sensation.
AB  - RATIONALE: Central processing of dyspnea relief remains largely unknown.
      OBJECTIVES: To identify physiologic determinants, quality of sensation, and brain
      activation associated with dyspnea relief. METHODS: Dyspnea relief was induced in
      10 healthy volunteers by decreasing an adjustable external resistive load (
      approximately 15-50 cm H(2)O/L/s). Brain imaging (positron emission tomography)
      was performed during either dyspnea or relief. MEASUREMENTS AND MAIN RESULTS:
      Perceived intensity of moderate and high relief was similar to that of its
      preceding dyspnea (Borg scores = 5.10 +/- 1.49 vs. 5.3 +/- 1.4, and 2.78 +/- 0.94
      vs. 2.99 +/- 0.94, respectively; P >/= 0.05) and was predominantly related to
      reversal of dyspnea-induced increased mouth pressure/ventilation ratio (r(2) =
      0.88, P < 0.001). Dyspnea relief involved specific, mostly positively valenced
      descriptors (i.e., breathing-related pleasure and/or reward). Most significant
      relief-associated brain activation was detected in the left anterior cingulate
      cortex (Z score = 4.7, corrected P < 0.05) and additional activation (uncorrected
      P < 0.0001) in the posterior cerebellum and in the temporal and prefrontal
      cortices. For dyspnea, significant activation was located in the right caudate
      nucleus, the anterior cerebellum (Z = 5 and 4.65, respectively; corrected P <
      0.05), and the premotor cortex, whereas deactivation occurred in the left
      prefrontal cortex (Z = 4.11). CONCLUSIONS: Relief of acute load-induced dyspnea
      is not simply the neutral perception of dyspnea decrease but rather a strong,
      positively valenced sensation that is associated with characteristic brain
      activation distinct from that subserving dyspnea perception and possibly
      reflecting activation of a dyspnea modulation network.

PMID- 18048809
TI  - Ozone, oxidant defense genes, and risk of asthma during adolescence.
AB  - RATIONALE: Although oxidative stress is a cardinal feature of asthma, the roles
      of oxidant air pollutants and antioxidant genes heme oxygenase 1 (HMOX-1),
      catalase (CAT), and manganese superoxide dismutase (MNSOD) in asthma pathogenesis
      have yet to be determined. OBJECTIVES: We hypothesized that the functional
      polymorphisms of HMOX-1 ([GT](n) repeat), CAT (-262C>T -844C>T), and MNSOD (Ala
      9Val) are associated with new-onset asthma, and the effects of these variants
      vary by exposure to ozone, a potent oxidant air pollutant. METHODS: We assessed
      this hypothesis in a population-based cohort of non-Hispanic (n = 1,125) and
      Hispanic white (n = 586) children who resided in 12 California communities and
      who were followed annually for 8 years to ascertain new-onset asthma.
      MEASUREMENTS AND MAIN RESULTS: Air pollutants were continuously measured in each
      of the study communities during the 8 years of study follow-up. HMOX-1 "short"
      alleles (<23 repeats) were associated with a reduced risk for new-onset asthma
      among non-Hispanic whites (hazard ratio [HR], 0.64; 95% confidence interval [CI],
      0.41-0.99). This protective effect was largest in children residing in low-ozone
      communities (HR, 0.48; 95% CI, 0.25-0.91) (interaction P value = 0.003). Little
      evidence for an association with HMOX-1 was observed among Hispanic children. In
      contrast, Hispanic children with a variant of the CAT-262 "T" allele (CT or TT)
      had an increased risk for asthma (HR, 1.78; P value = 0.01). The effects of these
      polymorphisms were not modified by personal smoking or secondhand-smoke exposure.
      CONCLUSIONS: Functional promoter variants in CAT and HMOX-1 showed ethnicity
      specific associations with new-onset asthma. Oxidant gene protection was
      restricted to children living in low-ozone communities.

PMID- 18048810
TI  - Interaction between smoking and genetic factors in the development of chronic
      bronchitis.
AB  - RATIONALE: Smoking is a primary risk factor for chronic bronchitis, emphysema,
      and chronic obstructive pulmonary disease, but since not all smokers develop
      disease, it has been suggested that some individuals may be more susceptible to
      exogenous factors, such as smoking, and that this susceptibility could be
      genetically determined. OBJECTIVES: The aim of the present study was to assess,
      in a population-based sample of twins, the following: (1) to what extent genetic
      factors contribute to the development of chronic bronchitis, including emphysema,
      taking sex into consideration, and (2) whether the genetic influences on chronic
      bronchitis, including emphysema, are separate from those for smoking behavior.
      METHODS: Disease cases and smoking habits were identified in 44,919 twins older
      than 40 years from the Swedish Twin Registry. Disease was defined as self
      reported chronic bronchitis or emphysema, or recurrent cough with phlegm.
      Individuals who had smoked 10 pack-years or more were defined as smokers.
      Univariate and bivariate structural equation models were used to estimate the
      heritability specific for chronic bronchitis and that in common with smoking.
      MEASUREMENTS AND MAIN RESULTS: The heritability estimate for chronic bronchitis
      was a moderate 40% and only 14% of the genetic influences were shared with
      smoking. CONCLUSIONS: Genetic factors independent of those related to smoking
      habits play a role in the development of chronic bronchitis.

PMID- 18048811
TI  - p53: it has it all, but will it make it to the clinic as a marker in bladder
      cancer?

PMID- 18048812
TI  - Should patient-reported outcomes be mandatory for toxicity reporting in cancer
      clinical trials?

PMID- 18048813
TI  - Moving beyond guidelines to improve the quality of care for men with prostate
      cancer.

PMID- 18048814
TI  - Incorporation of geriatric principles in oncology clinical trials.

PMID- 18048815
TI  - p53 gene and protein status: the role of p53 alterations in predicting outcome in
      patients with bladder cancer.
AB  - PURPOSE: The p53 gene status (mutation) and protein alterations (nuclear
      accumulation detectable by immunohistochemistry; p53 protein status) are
      associated with bladder cancer progression. Substantial discordance is documented
      between the p53 protein and gene status, yet no studies have examined the
      relationship between the gene-protein status and clinical outcome. This study
      evaluated the clinical relationship of the p53 gene and protein statuses.
      MATERIALS AND METHODS: The complete coding region of the p53 gene was queried
      using DNA from paraffin-embedded tissues and employing a p53 gene-sequencing
      chip. We compared p53 gene status, mutation site, and protein status with time to
      recurrence. RESULTS: The p53 gene and protein statuses show significant
      concordance, yet 35% of cases showed discordance. Exon 5 mutations demonstrated a
      wild-type protein status in 18 of 22 samples. Both the p53 gene and protein
      statuses were significantly associated with stage and clinical outcome. Specific
      mutation sites were associated with clinical outcome; tumors with exon 5
      mutations showed the same outcome as those with the wild-type gene. Combining the
      p53 gene and protein statuses stratifies patients into three distinct groups,
      based on recurrence-free intervals: patients showing the best outcome (wild-type
      gene and unaltered protein), an intermediate outcome (either a mutated gene or an
      altered protein) and the worst outcome (a mutated gene and an altered protein).
      CONCLUSION: We show that evaluation of both the p53 gene and protein statuses
      provides information in assessing the clinical recurrence risk in bladder cancer
      and that the specific mutation site may be important in assessing recurrence
      risk. These findings may substantially impact the assessment of p53 alterations
      and the management of bladder cancer.

PMID- 18048816
TI  - Characteristics of urologists predict the use of androgen deprivation therapy for
      prostate cancer.
AB  - PURPOSE: We previously have reported wide variations among urologists in the use
      of androgen deprivation for prostate cancer. Using the Surveillance,
      Epidemiology, and End Results-Medicare linked database, we examined how
      individual urologist characteristics influenced the use of androgen deprivation
      therapy. METHODS: Participants included 82,375 men with prostate cancer who were
      diagnosed from January 1, 1992, through December 31, 2002, and the 2,080
      urologists who provided care to them. Multilevel analyses were used to estimate
      the likelihood of androgen deprivation use within 6 months of diagnosis in the
      overall cohort, in a subgroup in which use would be of uncertain benefit (primary
      therapy for localized prostate cancer), and in a subgroup in which use would be
      evidence-based (adjuvant therapy with radiation for locally advanced disease).
      RESULTS: In the overall cohort of patients, a multilevel model adjusted for
      patient characteristics, tumor characteristics, and urologist characteristics
      (eg, board certification, academic affiliation, patient panel size, years since
      medical school graduation) showed that the likelihood of androgen deprivation use
      was significantly greater for patients who saw urologists without an academic
      affiliation. This pattern also was noted when the analysis was limited to
      settings in which androgen deprivation would have been of uncertain benefit. Odds
      ratios for use in that context were 1.66 (95% CI, 1.27 to 2.16) for urologists
      with no academic affiliation and 1.45 (95% CI, 1.13 to 1.85) for urologists with
      minor versus major academic affiliations. CONCLUSION: Use of androgen deprivation
      for prostate cancer varies by the characteristics of the urologist. Patients of
      non-academically affiliated urologists were significantly more likely to receive
      primary androgen deprivation therapy for localized prostate cancer, a setting in
      which the benefits are uncertain.

PMID- 18048817
TI  - Is there a role for pelvic irradiation in localized prostate adenocarcinoma?
      Preliminary results of GETUG-01.
AB  - PURPOSE: To assess the benefit and toxicity and quality-of-life (QOL) outcomes of
      pelvic nodes irradiation in nonmetastatic prostate carcinoma patients. PATIENTS
      AND METHODS: Between December 1998 and June 2004, 444 patients with T1b-T3, N0
      pNx, M0 prostate carcinoma were randomly assigned to either pelvic and prostate
      radiotherapy or prostate radiotherapy only. Patients were stratified according to
      the prognostic factor of lymph node involvement (LNI). Short-term 6-month
      neoadjuvant and concomitant hormonal therapy was allowed only for patients in the
      high-risk group. The pelvic dose was 46 Gy. The total dose recommended to the
      prostate was changed during the course of the study from 66 Gy to 70 Gy. Criteria
      for progression-free survival (PFS) included biologic prostate-specific antigen
      recurrences or a local or metastatic evolution. Acute and late toxicities were
      recorded according to the Radiation Therapy Oncology Group and Late Effects in
      Normal Tissues Subjective, Objective, Management, and Analytic scales,
      respectively. The QOL outcome was recorded with the European Organisation for
      Research and Treatment of Cancer Quality of Life Questionnaire C30, the
      International Prostatic Symptom Score, and the Sexual Function Index scales.
      RESULTS: With a 42.1-month median follow-up time, the 5-year PFS and overall
      survival were similar in the two treatment arms for the whole series and for each
      stratified group. On multivariate analysis, low LNI risk and hormonal therapy
      were statistically associated with increased PFS. However, subgroup analyses
      based on these factors did not show any benefit for pelvic irradiation. There
      were no significant differences in acute and late digestive toxicities and in QOL
      outcomes. CONCLUSION: Pelvic node irradiation was well tolerated but did not
      improve PFS.

PMID- 18048818
TI  - Long-term toxicity monitoring via electronic patient-reported outcomes in
      patients receiving chemotherapy.
AB  - PURPOSE: In cancer treatment trials, clinicians traditionally report patient
      toxicity symptoms. Alternatively, patients could provide this information
      directly. PATIENTS AND METHODS: The Common Terminology Criteria for Adverse
      Events (CTCAE) is the mandated instrument for tracking patient toxicity symptoms
      in National Cancer Institute (NCI)-sponsored cancer treatment trials. We adapted
      CTCAE symptom items into patient language and uploaded these to an online
      platform. Lung cancer outpatients receiving chemotherapy were invited to self
      report selected symptoms at visits via waiting area computers or optional home
      access. Symptom reports were printed for nurses at visits, but no instructions
      were given with regard to use of this information. RESULTS: From June 2005
      through March 2006, 125 patients were invited to participate, and 107 chose to
      enroll. Mean length of participation was 42 weeks (range, 1 to 71 weeks), by
      which time 35% died. The average number of clinic visits was 12 (range, 1 to 40
      visits). At each consecutive visit, most patients (mean, 78%) logged in without
      significant attrition. Reasons for failure to log in included having no reminder
      and having inadequate time. Although 76% of enrollees had home computers, only
      15% self-reported from home. Satisfaction with the system was high (90%), but
      only 51% felt communication was improved. All participating nurses understood the
      reports and felt this information was useful for clinical decisions,
      documentation, and discussions. However, only one of seven nurses discussed
      reports with patients frequently, with insufficient time being the most common
      barrier to discussions. CONCLUSION: Online patient self-reporting is a feasible
      long-term strategy for toxicity symptom monitoring during chemotherapy, even
      among patients with advanced cancer and high symptom burdens. However, without
      explicit reminders and clinician feedback, patients demonstrated limited
      voluntary interest in self-reporting between visits.

PMID- 18048819
TI  - Symptom prevalence, intensity, and distress in patients with inoperable lung
      cancer in relation to time of death.
AB  - PURPOSE: To examine symptom prevalence, intensity, and association with distress
      in patients with inoperable lung cancer (LC), using time to death as point of
      reference. PATIENTS AND METHODS: A consecutive sample of 400 patients completed
      the European Organisation for Research and Treatment of Cancer Quality of Life
      Questionnaire C30 plus a 13-item LC-specific scale and the Thurstone Scale of
      Symptom Distress-Lung Cancer at six time points during the first year after
      diagnosis. Patients were divided into subgroups, using data from the time point
      closest to death (< 1; 1 to 2; > 2 to 3; > 3 to 6; > 6 to 12; and > 12 months
      before death) for analysis. RESULTS: More than 50% of patients in all subgroups
      reported problems related to physical, role, and emotional functioning; fatigue;
      dyspnea; and cough. In general, functional levels were lower and symptoms higher
      in subgroups closer to death. Notably, clinically relevant differences were also
      found in role and social functioning and appetite loss between the two groups
      furthest from death. A consistent pattern was found among the six subgroups, with
      breathing, pain, and fatigue rated as the symptoms most associated with distress.
      CONCLUSION: High prevalence of symptoms was found in all subgroups, with higher
      intensity in subgroups closer to death, indicating a need for prophylactic and
      proactive symptom management. Less concordance was found among symptom
      prevalence, intensity, and association with distress in subgroups further from
      death. Future studies should investigate longitudinal associations between
      symptoms with low intensity and high distress, and examine their clinical
      implications.

PMID- 18048820
TI  - Randomized double-blind trial of prophylactic oral minocycline and topical
      tazarotene for cetuximab-associated acne-like eruption.
AB  - PURPOSE: To evaluate the ability of either oral minocycline, topical tazarotene
      or both, to reduce or prevent cetuximab-related acneiform rash when administered
      starting on day 1 of cetuximab therapy. PATIENTS AND METHODS: Metastatic
      colorectal cancer patients preparing to initiate cetuximab were randomly assigned
      to receive daily oral minocycline or placebo, and to receive topical tazarotene
      application to either left or right side of the face. Both therapies were
      administered for 8 weeks. RESULTS: Forty-eight eligible patients were randomly
      assigned to minocycline (n = 24) or placebo (n = 24). Total facial lesion counts
      were significantly lower in patients receiving minocycline at weeks 1 through 4.
      At week 4, a lower proportion of patients in the minocycline arm reported
      moderate to severe itch than in the placebo arm (20% v 50%, P = .05). Facial
      photographs, obtained at week 4, were reviewed for rash global severity. Patients
      in the minocycline arm trended toward lower frequency of moderate to severe rash
      than patients receiving placebo (20% v 42%, P = .13). The differences in total
      facial lesion counts and subjectively assessed itch were diminished by week 8.
      Cetuximab treatment was interrupted because of grade 3 skin rash in four patients
      in the placebo arm, and none in the minocycline arm. There was no observed
      clinical benefit to tazarotene application. Tazarotene treatment was associated
      with significant irritation, causing its discontinuation in one third of
      patients. CONCLUSION: Prophylaxis with oral minocycline may be useful in
      decreasing the severity of the acneiform rash during the first month of cetuximab
      treatment. Topical tazarotene is not recommended for management of cetuximab
      related rash.

PMID- 18048821
TI  - Phase II study of uracil-tegafur with leucovorin in elderly (> or = 75 years old)
      patients with colorectal cancer: ECOG 1299.
AB  - PURPOSE: To evaluate the tolerability and effectiveness of uracil-tegafur (UFT)
      with leucovorin (LV) in the treatment of elderly patients with advanced
      colorectal cancer. PATIENTS AND METHODS: Patients > or = 75 years of age with
      previously untreated colorectal cancer were eligible for this phase II, single
      arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus
      LV 30 mg orally every 8 hours for 28 days every 35 days was administered until
      progression. RESULTS: Fifty-eight patients were enrolled between June 2000 and
      July 2001, and 55 were treated. The median age of treated patients was 81 years
      (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good
      performance status (0 to 1). The observed overall response rate was 22% (95% CI,
      11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95%
      CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months
      (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one
      ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly
      diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at
      highest risk. CONCLUSION: The results of this trial support the efficacy of oral
      UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated
      moderately well overall, particularly as compared with other fluoropyrimidine
      regimens, although there is increased GI toxicity in the most elderly. These
      results suggest that studies using newer oral fluoropyrimidine analogs should be
      investigated in this patient population.

PMID- 18048822
TI  - Prospective study of long-term impact of adjuvant high-dose and conventional-dose
      chemotherapy on health-related quality of life.
AB  - PURPOSE: To evaluate and compare health-related quality of life (HRQOL) after
      conventional- and high-dose adjuvant chemotherapy in patients with high-risk
      breast cancer. PATIENTS AND METHODS: Patients were randomly assigned to either a
      conventional or high-dose chemotherapy regimen; both regimens were followed by
      radiotherapy and tamoxifen. HRQOL was evaluated until disease progression using
      the Short Form-36 (SF-36), Visual Analog Scale, and Rotterdam Symptom Checklist
      and assessed every 6 months for 5 years after random assignment. For the SF-36,
      data from healthy Dutch women with the same age distribution served as reference
      values. RESULTS: Eight hundred four patients (conventional-dose chemotherapy, n =
      405; high-dose chemotherapy, n = 399) were included. Median follow-up time was 57
      months. Directly after high-dose chemotherapy, HRQOL decreased more compared with
      conventional chemotherapy for all SF-36 subscales. After 1 year, the reference
      value of healthy women was reached in both groups. Small differences were
      observed between the two groups in the role-physical and role-emotional
      subscales, but 1 year after treatment, these differences were minor and not
      clinically relevant. During follow-up, patients with a lower educational level
      and many complaints before chemotherapy experienced a worse HRQOL. CONCLUSION:
      Shortly after high-dose chemotherapy, HRQOL was more affected than after
      conventional-dose chemotherapy. One year after random assignment, differences
      were negligible. Identifying patients who have a higher chance of persistent
      impaired quality of life after treatment (which, in the present study, included
      patients with a lower educational level and many complaints before chemotherapy)
      is important and may open the way for better patient-tailored prevention
      strategies.

PMID- 18048823
TI  - Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active
      in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose
      escalation study.
AB  - PURPOSE: This phase I study examined whether a heat shock protein (Hsp) 90
      inhibitor tanespimycin (17-AAG; KOS-953) could be administered safely in
      combination with trastuzumab at a dose that inhibits Hsp90 function in vivo in
      lymphocytes. PATIENTS AND METHODS: Patients with an advanced solid tumor
      progressing during standard therapy were eligible. Patients were treated with
      weekly trastuzumab followed by intravenous tanespimycin, assessed in escalating
      dose levels. RESULTS: Twenty-five patients were enrolled onto four tanespimycin
      dose levels: 225 (n = 4), 300 (n = 3), 375 (n = 8), and 450 mg/m2 (n = 10). Dose
      limiting toxicity (DLT) was observed at the third and fourth cohort (1 patient
      each): more than 2-week delay for grade 4 fatigue/grade 2 nausea and anorexia
      (375 mg/m2); more than 2-week delay for thrombocytopenia (450 mg/m2). Drug
      related grade 3 toxicity included emesis, increased ALT, hypersensitivity
      reactions (two patients each), and drug-induced thrombocytopenia (n = 1). Common
      mild to moderate toxicities included fatigue, nausea, diarrhea, emesis, headache,
      rash/pruritus, increased AST/ALT, and anorexia. Pharmacokinetic analysis
      demonstrated no difference in tanespimycin kinetics with or without trastuzumab.
      Pharmacodynamic testing showed reactive induction of Hsp70 (a marker of Hsp90
      inhibition) in lymphocytes at all dose levels. Antitumor activity was noted
      (partial response, n = 1; minor response, n = 4; stable disease > or = 4 months,
      n = 4). Tumor regressions were seen only in patients with human epidermal growth
      factor receptor 2 (HER-2)-positive metastatic breast cancer. CONCLUSION:
      Tanespimycin plus trastuzumab is well tolerated and has antitumor activity in
      patients with HER-2+ breast cancer whose tumors have progressed during treatment
      with trastuzumab. These data suggest that Hsp90 function can be inhibited in vivo
      to a degree sufficient to cause inhibition of tumor growth.

PMID- 18048824
TI  - Quantitative justification of the change from 10% to 30% for human epidermal
      growth factor receptor 2 scoring in the American Society of Clinical
      Oncology/College of American Pathologists guidelines: tumor heterogeneity in
      breast cancer and its implications for tissue microarray based assessment of
      outcome.
AB  - PURPOSE: The variability in scoring of immunohistochemistry, whether a result of
      true heterogeneity or artifacts in preparation, has led to decreased reliability
      in companion diagnostics and the recommendation for new standards (eg, the
      American Society of Clinical Oncology/College of American Pathologists [ASCO-CAP]
      guidelines). The basis of this problem is the amount of tissue required to be
      representative of an entire tumor. Because protein expression on tissue
      microarrays (TMAs) can be rigorously measured and one 0.6-mm spot is equivalent
      to two to three high-power fields, we used TMAs to assess levels of heterogeneity
      and to determine optimal representation as a function of outcome. PATIENTS AND
      METHODS: We analyzed estrogen receptor (ER), progesterone receptor, and human
      epidermal growth factor receptor 2 (HER-2) expression in two cohorts (n = 676 and
      n = 152) on a series of four to five separate TMA cores and assessed
      heterogeneity by linear regression analysis. Minimum, average, and maximum scores
      were generated for each set, which were then assessed for prognostic and
      predictive value. RESULTS: Each marker shows some heterogeneity, but average r
      values between 0.7 and 0.8 are seen between TMA spots. Analysis for prognostic
      value shows that the highest maximum score (of five spots) is the most prognostic
      for ER, whereas a high HER-2 minimum score is most prognostic for poor outcome
      and most predictive of response to trastuzumab. CONCLUSION: These results suggest
      that the representivity required for each biomarker may be a function of its role
      in tumorigenesis. Furthermore, these results provide scientific basis for the
      ASCO-CAP guidelines for assessment of HER-2 expression but perhaps suggest that
      the 30% figure is still too conservative.

PMID- 18048825
TI  - Chemotherapy compared with biochemotherapy for the treatment of metastatic
      melanoma: a meta-analysis of 18 trials involving 2,621 patients.
AB  - PURPOSE: To assess the effect of adding interferon-alpha (IFN) +/- interleukin-2
      (IL-2) to chemotherapy in patients with metastatic melanoma. METHODS A published
      data meta-analysis of trials of biochemotherapy versus chemotherapy in patients
      with metastatic melanoma was undertaken. End points evaluated were rates of
      partial response (PR), complete response (CR) and overall (partial + complete)
      response (OR); response duration; progression-free survival; overall survival
      (OS); and toxicity. The only subgroup analysis performed was by type of
      immunotherapy, with trials divided according to whether IFN only or IFN and IL-2
      were administered in the biochemotherapy arm. RESULTS: Eighteen randomized trials
      were identified: 11 trials of chemotherapy +/- IFN and seven trials of
      chemotherapy +/- IFN and IL-2. More than 2,600 patients were entered onto the
      trials, with 555 responses and 2,039 deaths. There was a clear benefit for
      biochemotherapy for PR (odds ratio = 0.66; 95% CI, 0.53 to 0.82; P = .0001), CR
      (odds ratio = 0.50; 95% CI, 0.35 to 0.73; P = .0003) and OR (odds ratio = 0.59;
      95% CI, 0.49 to 0.72; P < .00001). For OR, these benefits were significant for
      both the IFN (odds ratio = 0.60; 95% CI, 0.46 to 0.79; P = .0002) and IFN + IL-2
      (odds ratio = 0.58; 95% CI, 0.44 to 0.77; P = .0001) subgroups. In contrast,
      there was no benefit overall in OS (odds ratio = 0.99; 95% CI, 0.91 to 1.08; P =
      .9), but there was evidence of heterogeneity of treatment effect between the
      individual trials (P = .006). CONCLUSION: This meta-analysis provides a
      comprehensive summary of all the data currently available, and shows that
      although biochemotherapy clearly improves response rates, this does not appear to
      translate into a survival benefit.

PMID- 18048826
TI  - Positron emission tomography for staging of pediatric sarcoma patients: results
      of a prospective multicenter trial.
AB  - PURPOSE: The objective of this study was to evaluate the impact of positron
      emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) for initial
      staging and therapy planning in pediatric sarcoma patients. PATIENTS AND METHODS:
      In this prospective multicenter study, 46 pediatric patients (females, n = 22;
      males, n = 24; age range, 1 to 18 years) with histologically proven sarcoma
      (Ewing sarcoma family tumors, n = 23; osteosarcoma, n = 11; rhabdomyosarcoma, n =
      12) were examined with conventional imaging modalities (CIMs), including
      ultrasound, computed tomography (CT), magnetic resonance imaging, and bone
      scintigraphy according to the standardized algorithms of the international
      therapy optimization trials, and whole-body FDG-PET. A lesion- and patient-based
      analysis of PET alone and CIMs alone and a side-by-side (SBS) analysis of FDG-PET
      and CIMs were performed. The standard of reference consisted of all imaging
      material, follow-up data (mean follow-up time, 24 +/- 12 months), and
      histopathology and was determined by an interdisciplinary tumor board. RESULTS:
      FDG-PET and CIMs were equally effective in the detection of primary tumors
      (accuracy, 100%). PET was superior to CIMs concerning the correct detection of
      lymph node involvement (sensitivity, 95% v 25%, respectively) and bone
      manifestations (sensitivity, 90% v 57%, respectively), whereas CT was more
      reliable than FDG-PET in depicting lung metastases (sensitivity, 100% v 25%,
      respectively). The patient-based analysis revealed the best results for SBS, with
      91% correct therapy decisions. This was significantly superior to CIMs (59%; P <
      .001). CONCLUSION: In staging pediatric sarcoma, subsidiary FDG-PET scanning
      depicts important additional information and has a relevant impact on therapy
      planning when analyzed side-by-side with CIMs.

PMID- 18048827
TI  - Prospective study of a pirarubicin, intermediate-dose cytarabine, and etoposide
      regimen in children with Down syndrome and acute myeloid leukemia: the Japanese
      Childhood AML Cooperative Study Group.
AB  - PURPOSE: To evaluate a less intensive chemotherapeutic regimen specifically
      designed for patients with Down syndrome (DS) and acute myeloid leukemia (AML),
      and to determine the prognostic factors for event-free survival. PATIENTS AND
      METHODS: Seventy-two patients with AML-DS were treated with remission induction
      chemotherapy consisting of pirarubicin (25 mg/m2/d for 2 days), cytarabine (100
      mg/m2/d for 7 days), and etoposide (150 mg/m2/d for 3 days). Patients received
      four courses of intensification therapy of the same regimen. Prophylaxis for CNS
      leukemia was not included. RESULTS: All but two patients were younger than 4
      years, and 67 of the 72 patients (93%) were diagnosed as acute megakaryoblastic
      leukemia (AMKL). Seventy of the 72 patients (97.2%) achieved a complete remission
      (CR), and the estimated 4-year event-free survival (EFS) rate was 83% +/- 9%.
      Nine patients relapsed, and one died as a result of pneumonia during CR.
      Multivariate analysis revealed that the presence of monosomy 7 was a greater risk
      factor of adverse outcome (odds ratio = 5.67; P = .027). CONCLUSION: A less
      intensive chemotherapeutic regimen produces excellent outcomes in standard-risk
      AML-DS patient. Risk-oriented therapy should be considered for future trials in
      AML-DS.

PMID- 18048829
TI  - Spontaneous rupture of the spleen in the presentation of acute myeloid leukemia.

PMID- 18048828
TI  - Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using
      intra-Ommaya 131-I-3F8.
AB  - PURPOSE: Tumors metastasizing to the CNS and leptomeninges (LM) are associated
      with significant mortality. We tested the toxicity, pharmacokinetics, and
      dosimetry of intraventricular iodine-131-labeled monoclonal antibody 3F8 (131I
      3F8) targeting GD2-positive CNS/LM disease in a phase I clinical trial. PATIENTS
      AND METHODS: Adequate CSF flow was determined by pretreatment indium-111-DTPA
      studies. Fifteen patients received a tracer (1 to 2 mCi) and therapeutic
      injection (10 to 20 mCi) of intra-Ommaya 131I-3F8. 131I-3F8 pharmacokinetics were
      studied by serial CSF and blood samplings. Dosimetry was based on
      pharmacokinetics and region of interest (ROI) analyses on whole-body gamma camera
      scans. Tumor response was determined by clinical, radiographic, and cytologic
      criteria. RESULTS: Total absorbed CSF dose was 1.12 to 13.00 Gy by sampling and
      1.00 to 13.70 Gy by ROI data. Average dosimetry ratio (Gy/mCi) of the
      therapy/tracer administration was 0.88 (+/- 0.58) and 1.08 (+/- 0.66) based on
      CSF pharmacokinetics and ROI analysis, respectively. CSF half-life by sampling
      was 3 to 12.9 hours. Toxicities included self-limited headache, fever, and
      vomiting. Dose-limiting toxicity was reached at the 20-mCi dose, when transient
      elevations in intracranial pressure and chemical meningitis were seen. Three of
      13 assessable patients achieved objective radiographic and/or cytologic
      responses. No late toxicities have been seen in two patients who remain in
      remission off therapy for more than 3.5 years. CONCLUSION: Intra-Ommaya 131I-3F8
      was generally well tolerated; the maximum-tolerated dose was 10 mCi. A high CSF
      to-blood ratio was achieved. Tracer studies reliably predicted the therapeutic
      dose to the CSF. Radioimmunoconjugates targeting GD2 may have clinical utility in
      the treatment of CNS/LM malignancies.

PMID- 18048831
TI  - Unilateral lymphoma-related leg edema.

PMID- 18048830
TI  - Unresectable adenoid cystic carcinoma of the trachea treated with chemoradiation.

PMID- 18048832
TI  - Souvenir children: death and rebirth.

PMID- 18048833
TI  - Doubts about whether docetaxel, cisplatin, plus fluorouracil has any benefit in
      advanced gastric cancer.

PMID- 18048834
TI  - The area between the curves gets no respect: is it because of the median madness?

PMID- 18048835
TI  - Reversibility of trastuzumab cardiotoxicity: is the concept alive and well?

PMID- 18048836
TI  - Low affordability may limit the effect of cervical cancer vaccination in central
      and eastern European countries.

PMID- 18048837
TI  - Lung cancer survival: vitamin D could be just a marker of physical fitness.

PMID- 18048838
TI  - The common rs9939609 gene variant of the fat mass- and obesity-associated gene
      FTO is related to fat cell lipolysis.
AB  - We investigated the rs9939609 single nucleotide polymorphism of the FTO gene in
      relation to fat cell function and adipose tissue gene expression in 306 healthy
      women with a wide range in body mass index (18-53 kg/m(2)). Subcutaneous adipose
      tissue biopsies were taken for fat cell metabolism studies and in a subgroup (n =
      90) for gene expression analyses. In homozygous carriers of the T-allele, the in
      vitro basal (spontaneous) adipocyte glycerol release was increased by 22% (P =
      0.007) and the in vivo plasma glycerol level was increased by approximately 30%
      (P = 0.037) compared with carriers of the A allele. In contrast, there were no
      genotype effects on catecholamine-stimulated lipolysis or basal or insulin
      induced lipogenesis. We found no difference between genotypes for adipose tissue
      mRNA levels of FTO, hormone-sensitive lipase, adipose triglyceride lipase,
      perilipin, or CGI-58. Finally, the adipose tissue level of FTO mRNA was increased
      in obesity (P = 0.002), was similar in subcutaneous and omental adipose tissue,
      was higher in fat cells than in fat tissue (P = 0.0007), and was induced at an
      early stage in the differentiation process (P = 0.004). These data suggest a role
      of the FTO gene in fat cell lipolysis, which may be important in explaining why
      the gene is implicated in body weight regulation.

PMID- 18048839
TI  - Prevalence of intracranial atherosclerosis and coexistent conditions in ethnic
      South Asians.

PMID- 18048840
TI  - The continued yin and yang of uric acid.

PMID- 18048841
TI  - Arrival time to stroke unit as crucial a measure as arrival time to emergency
      department.

PMID- 18048842
TI  - Infection and brain-induced immunodepression after acute ischemic stroke.

PMID- 18048843
TI  - Comments regarding the recent OAST article.

PMID- 18048844
TI  - Cholesterol measured before stroke thrombolysis is not associated with tissue
      plasminogen activator-related hemorrhagic transformation.

PMID- 18048845
TI  - Methodological quality and publication bias in observational studies on risk of
      rupture of unruptured intracranial aneurysms.

PMID- 18048846
TI  - The First Consensus Document of ICCS-SPREAD Joint Committee on Carotid Artery
      Stenting was not premature but prophetic.

PMID- 18048847
TI  - Risk of high dose hydrocortisone in patients with aneurysmal subarachnoid
      hemorrhage.

PMID- 18048848
TI  - Carotid angioplasty and stenting.

PMID- 18048849
TI  - Barriers to anticoagulation in patients with atrial fibrillation: changing
      physician-related factors.

PMID- 18048850
TI  - Carotid intervention in asymptomatic patients.

PMID- 18048851
TI  - Sex differences in acute stroke care in a statewide stroke registry.
AB  - BACKGROUND AND PURPOSE: Many studies have reported poorer stroke outcomes in
      women, and some studies have reported sex differences in care. We analyzed data
      from a hospital-based stroke registry to determine whether acute stroke care and
      discharge status differed by sex. METHODS: Detailed chart-level information was
      collected on 2566 subjects admitted for acute stroke or transient ischemic attack
      to 15 Michigan hospitals in 2002. Sex differences in stroke care and patient
      status at discharge (in-hospital mortality and modified Rankin Scale score) were
      assessed after adjusting for differences in demographics, clinical
      characteristics, and comorbidities by multivariable models. Modified Rankin Scale
      score data were analyzed by proportional-odds models. RESULTS: Women were older
      than men (70 vs 67 years) and were more likely to have congestive heart failure
      and hypertension. Men were more likely to smoke and have a history of heart
      disease and dyslipidemia. After multivariable adjustment, women were less likely
      to receive thrombolytic therapy (odds ratio [OR]=0.56; 95% CI, 0.37 to 0.86) or
      lipid testing (OR=0.76; 95% CI, 0.61 to 0.94) and were more likely to suffer
      urinary tract infections (OR=2.57; 95% CI, 1.87 to 3.54). In-hospital mortality
      was similar in women and men (9% vs 8%); however, women had poorer discharge
      modified Rankin Scale scores (OR=1.17; 95% CI, 1.01 to 1.35). CONCLUSIONS:
      Although considerable parity exists in many aspects of acute stroke care, women
      were less likely than men to receive thrombolytic treatment and lipid testing,
      even after adjustment. However, given the largely similar care observed, it is
      unlikely that differences in care explain the poorer functional outcomes in
      female stroke survivors.

PMID- 18048853
TI  - Handicap and its determinants of change in stroke survivors: one-year follow-up
      study.
AB  - BACKGROUND AND PURPOSE: Stroke, a major health issue affecting the elderly,
      limits their participation in society. The aim of this study was to investigate
      changes in stroke survivors' handicap levels and to identify their determinants
      in the subacute phase from 3 months to 1 year. METHODS: Data were collected from
      a prospective cohort of 303 Chinese stroke survivors with the use of
      questionnaires, including the Lawton Instrumental Activities of Daily Living
      Chinese Version (IADL-CV), Barthel Index, Chinese Mini-Mental State Examination,
      Chinese Geriatric Depression Scale, and the Chinese version of the London
      Handicap Scale. RESULTS: A total of 297 and 268 patients were successfully
      followed up at 6 and 12 months, respectively. Whereas IADL remained unchanged
      throughout, we found an improvement in Barthel Index but a deterioration in the
      Chinese Geriatric Depression Scale score at 12 months. Multilevel modeling
      revealed improvements in the mobility and social integration handicap domains and
      a deterioration in the orientation domain at 12 months. Overall handicap remained
      unchanged. At 12 months, depression was most significantly and independently
      associated with poststroke handicap, and advanced old age alone (>80 years) was
      associated with clinically significant deterioration in handicap. CONCLUSIONS:
      Even though IADL remained static at 1 year, mobility and social integration
      handicap dimensions can be improved in the early community phase after stroke.
      Nonphysical factors such as depression were confirmed to be significantly
      associated with handicap. Rehabilitation should target the high-risk group of
      very elderly stroke survivors who were 4 times more likely to deteriorate in
      handicap.

PMID- 18048854
TI  - Selective expansion of influenza A virus-specific T cells in symptomatic human
      carotid artery atherosclerotic plaques.
AB  - BACKGROUND AND PURPOSE: Evidence is accumulating that infection with influenza A
      virus contributes to atherothrombotic disease. Vaccination against influenza
      decreases the risk of atherosclerotic syndromes, indicating that inflammatory
      mechanisms may be involved. We tested the hypothesis that influenza A virus
      specific T cells contribute to atherosclerotic plaque inflammation, which
      mediates the onset of plaque rupture. METHODS: T-cell cultures were generated
      from atherosclerotic segments and peripheral blood of 30 patients with
      symptomatic carotid artery disease. The response of plaque and peripheral blood T
      cells to influenza A virus was analyzed and expressed as a stimulation index
      (SI). Selective outgrowth of intraplaque influenza A-specific T cells was
      calculated by the ratio of plaque T cell SI and peripheral blood T cell SI for
      each patient. Accordingly, the patients were categorized as high- (SI ratio
      >or=5), intermediate- (5 <SI ratio <or=2), and non- (SI ratio <2) responders. The
      presence of influenza A virus in the vessel fragments was evaluated by reverse
      transcription-polymerase chain reaction. RESULTS: High proliferative responses of
      plaque-derived T cells to influenza A virus were frequently observed. Among the
      30 patients, 5 were categorized as high responders, 10 were intermediate
      responders, and 15 were nonresponders. Live influenza A virus could not be
      detected in the atherosclerotic plaques by polymerase chain reaction.
      CONCLUSIONS: Selective outgrowth of influenza A virus-specific T cells occurs
      within the microenvironment of human atherosclerotic plaques. Influenza virus
      derived antigens or alternatively, mimicry antigens, appear to be potential
      candidates for triggering or sustaining plaque inflammation, which eventually
      leads to symptomatic plaque complications.

PMID- 18048852
TI  - Quantitative trait locus analysis of carotid atherosclerosis in an intercross
      between C57BL/6 and C3H apolipoprotein E-deficient mice.
AB  - BACKGROUND AND PURPOSE: Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H)
      exhibit marked differences in atherosclerotic lesion formation in the carotid
      arteries on the apolipoprotein E-deficient (apoE(-/-)) background when fed a
      Western diet. Quantitative trait locus analysis was performed on an intercross
      between B6.apoE(-/-) and C3H.apoE(-/-) mice to determine genetic factors
      contributing to variation in the phenotype. METHODS: Female B6.apoE(-/-) mice
      were crossed with male C3H.apoE(-/-) mice to generate F(1) hybrids, which were
      intercrossed to generate 241 female F(2) progeny. At 6 weeks of age, F(2) mice
      were started on a Western diet. After being fed the diet for 12 weeks, F(2) mice
      were analyzed for phenotypes such as lesion size in the left carotid arteries and
      plasma lipid levels and typed for 154 genetic markers spanning the mouse genome.
      RESULTS: One significant quantitative trait locus, named CAth1 (25 cM, log of the
      odds score: 4.5), on chromosome 12 and 4 suggestive quantitative trait loci, on
      chromosomes 1, 5, 6, and 11, respectively, were identified to influence carotid
      lesion size. One significant quantitative trait locus on distal chromosome 1
      accounted for major variations in plasma low-density lipoprotein/very-low-density
      lipoprotein, high-density lipoprotein cholesterol, and triglyceride levels.
      Carotid lesion size was not significantly correlated with plasma low-density
      lipoprotein/very-low-density lipoprotein or high-density lipoprotein cholesterol
      levels. CONCLUSIONS: These data indicate that the loci for carotid lesions do not
      overlap with those for aortic lesions as identified in a previous cross derived
      from the same parental strains, and carotid atherosclerosis and plasma lipids are
      controlled by separate genetic factors in the B6 and C3H mouse model.

PMID- 18048855
TI  - Prevalence and clinicoepidemiological features of moyamoya disease in Japan:
      findings from a nationwide epidemiological survey.
AB  - BACKGROUND AND PURPOSE: The objectives of the present study were to estimate an
      annual number of patients with moyamoya disease in Japan and to describe the
      clinicoepidemiological features of the disease. METHODS: The study consisted of 2
      questionnaire surveys, which were distributed to randomly selected departments of
      neurosurgery, internal medicine, neurology, cerebrovascular medicine, and
      pediatrics in hospitals throughout Japan. The first survey inquired about the
      number of the patients treated in 2003, and the second requested additional
      detailed clinicoepidemiological information about each patient identified in the
      first survey. RESULTS: In 2003, the total number of patients treated in Japan was
      estimated at 7700 (95% confidence interval, 6300 to 9300). Sex ratio (women to
      men) of the patients was 1.8. For men, the peak of moyamoya disease was observed
      in patients aged 10 to 14 years and for women aged 20 to 24 years. Annual rate of
      newly diagnosed cases in 2003 was 0.54 per 100,000 population. Family history of
      moyamoya disease was found in 12.1% of the patients. The majority (77.9%) were
      treated as outpatients. CONCLUSIONS: Although the clinicoepidemiological features
      of the patients in the present study were almost similar to those obtained in
      previous ones, the estimated prevalence of moyamoya disease in Japan has almost
      doubled during the recent decade (3900 in 1994 and 7700 in 2003). The increase
      could partly be explained by the increase in newly diagnosed cases (0.35 in 1994
      and 0.54 in 2003 per 100,000 population).

PMID- 18048856
TI  - Experimental model of lacunar infarction in the gyrencephalic brain of the
      miniature pig: neurological assessment and histological, immunohistochemical, and
      physiological evaluation of dynamic corticospinal tract deformation.
AB  - BACKGROUND AND PURPOSE: Lacunar infarction accounts for 25% of ischemic strokes,
      but the pathological characteristics have not been investigated systematically. A
      new experimental model of lacunar infarction in the miniature pig was developed
      to investigate the pathophysiological changes in the corticospinal tract from the
      acute to chronic phases. METHODS: Thirty-five miniature pigs underwent
      transcranial surgery for permanent anterior choroidal artery occlusion. Animals
      recovered for 24 hours (n=7), 2 (n=5), 3 (n=2), 4 (n=2), 6 (n=1), 7 (n=7), 8
      (n=2), and 9 days (n=1), 2 weeks (n=2), 4 weeks (n=3), and more than 4 weeks
      (n=3). Neurology, electrophysiology, histology, and MRI were performed. Seven
      additional miniature pigs underwent transient anterior choroidal artery occlusion
      to study muscle motor-evoked potentials and evaluate corticospinal tract function
      during transient anterior choroidal artery occlusion. RESULTS: The protocol had a
      91.4% success rate in induction of internal capsule infarction 286+/-153 mm(3)
      (mean+/-SD). Motor-evoked potentials revealed the presence of penumbral tissue in
      the internal capsule after 6 to 15 minutes anterior choroidal artery occlusion.
      Total neurological deficit scores of 15.0 (95% CI, 13.5 to 16.4) and 3.4 (0.3 to
      6.4) were recorded for permanent anterior choroidal artery occlusion and sham
      groups, respectively (P<0.001, maximum score 25) with motor deficit scores of 3.4
      (95% CI, 2.9 to 4.0) and 0.0 (CI, 0.0 to 0.0), respectively (P<0.001, maximum
      score 9). Histology revealed that the internal capsule lesion expands gradually
      from acute to chronic phases. CONCLUSIONS: This new model of lacunar infarction
      induces a reproducible infarct in subcortical white matter with a measurable
      functional deficit and evidence of penumbral tissue acutely.

PMID- 18048857
TI  - Intramuscular botulinum toxin-A reduces hemiplegic shoulder pain: a randomized,
      double-blind, comparative study versus intraarticular triamcinolone acetonide.
AB  - BACKGROUND AND PURPOSE: Shoulder pain is frequent after stroke and interferes
      with the rehabilitative process and outcome. However, treatments used for
      hemiplegic shoulder pain are limited and largely ineffective. This prospective,
      randomized, double-blind controlled study was conducted to compare the efficacies
      of botulinum toxin type A (BoNT-A) and triamcinolone acetonide (TA) on hemiplegic
      shoulder pain and their effects on arm function in patients with stroke. METHODS:
      Twenty-nine hemiplegic stroke patients with shoulder pain (duration <or=24
      months, pain on numeric rating scale >or=6/10) were randomized into 2 groups. One
      group received intramuscular injections of BoNT-A (BOTOX 100 U total) during one
      session to the infraspinatus, pectoralis and subscapularis muscles in conjunction
      with an intraarticular injection of normal saline to painful shoulder joint,
      whereas the other group received an intraarticular injection of TA (40 mg) and an
      intramuscular injection of normal saline to the same muscles. Outcome measures
      were pain (measured using a numeric rating scale), physician's global rating
      scale, shoulder range of motion (ROM) in 4 directions, arm function measured
      using Fugl-Meyer score, and spasticity measured using the modified Ashworth
      scale. Measurements were made at baseline and 2, 6, and 12 weeks after injection.
      RESULTS: At 12 weeks after treatment mean decrease in pain was 4.2 in the BoNT-A
      treated group versus 2.5 in the TA-treated group (P=0.051), and improvements in
      overall ROM were 82.9 degrees versus 51.8 degrees in these groups (P=0.059),
      showing a strong trend toward there being less pain and better ROM among those
      treated with BoNT-A than with TA. However, no significant differences were
      observed between the 2 groups in terms of improvement in physician global rating,
      Fugl-Meyer score or modified Ashworth scales. No adverse effect was observed in
      either group. CONCLUSIONS: Results from this study suggest that injection of BoNT
      A into selected muscles of the shoulder girdle might provide more pain relief and
      ROM improvement than intraarticular steroid in patients with hemiplegic shoulder
      pain. A larger clinical trial needs to be undertaken to confirm the benefits of
      this approach.

PMID- 18048858
TI  - Treatment pathways, resource use, and costs of endovascular coiling versus
      surgical clipping after aSAH.
AB  - BACKGROUND AND PURPOSE: The International Subarachnoid Aneurysm Trial (ISAT)
      reported that endovascular coiling yields better clinical outcomes than surgical
      clipping at 1 year. The high cost of the consumables associated with the
      endovascular coiling procedure (particularly the coils) led health care
      purchasers to conclude that coiling was a more costly procedure overall. To
      examine this assumption and provide evidence for future policy, accurate and
      comprehensive data are required on the overall resource usage and cost of each
      strategy. METHODS: We provide detailed results of patient treatment pathways,
      resource utilization, and costs up to 24 months postrandomization for
      endovascular and neurosurgical treatment of aSAH. We report data on costs related
      to initial and subsequent procedures (ward days, ITU, equipment, staff,
      consumables, etc), adverse events, complications, and follow up. The data are
      based on a subsample of all patients randomized in ISAT, containing all patients
      across 22 UK centers (n=1644). RESULTS: There was a nonsignificant difference -
      pound 1740 (- pound 3582 to pound 32) in the total 12-month cost of treatment in
      favor of endovascular treatment. Endovascular patients had higher costs than
      neurosurgical patients for the initial procedure, for the number and length of
      stay of subsequent procedures, and for follow-up angiograms. These were more than
      offset by lower costs related to length of stay for the initial procedure. In the
      following 12- to 24-month period, costs for subsequent procedures, angiograms,
      complications, and adverse events were greater for the endovascular patients,
      reducing the difference in total per patient cost to - pound 1228 (- pound 3199
      to pound 786) over the first 24 months of follow-up. CONCLUSIONS: No significant
      difference in costs between the endovascular and neurosurgery groups existed at
      12- or 24-month follow up.

PMID- 18048859
TI  - Lessons about brain vascular disease from another pulsating organ, the kidney.

PMID- 18048860
TI  - Predictors of rehemorrhage after treatment of ruptured intracranial aneurysms:
      the Cerebral Aneurysm Rerupture After Treatment (CARAT) study.
AB  - BACKGROUND AND PURPOSE: The primary purpose of intracranial aneurysm treatment is
      to prevent rupture. Risk factors for rupture after aneurysm treatment have not
      been clearly established, and the need to completely occlude aneurysms is
      debated. METHODS: The Cerebral Aneurysm Rerupture After Treatment (CARAT) study
      is an ambidirectional cohort study of all patients with ruptured intracranial
      aneurysms treated with coil embolization or surgical clipping at 9 high-volume
      centers in the United States from 1996 to 1998. All subjects were followed
      through 2005, and all potential reruptures were adjudicated by a panel of 3
      specialists without knowledge of the initial treatment or aneurysm
      characteristics. Degree of aneurysm occlusion post-treatment was evaluated as a
      predictor of nonprocedural rerupture in univariate Kaplan-Meier analysis (log
      rank test) and in a Cox proportional-hazards model after adjustment for potential
      confounders and censoring at time of retreatment. RESULTS: Among 1001 patients
      during a mean of 4.0 years follow-up, there were 19 postprocedural reruptures;
      median time to rerupture was 3 days and 58% led to death. The degree of aneurysm
      occlusion after treatment was strongly associated with risk of rerupture (overall
      risk: 1.1% for complete occlusion, 2.9% for 91% to 99% occlusion, 5.9% for 70% to
      90%, 17.6% for <70%; P<0.0001 in univariate and multivariable analysis). Overall
      risk of rerupture tended to be greater after coil embolization compared with
      surgical clipping (3.4% versus 1.3%; P=0.092), but the difference did not persist
      after adjustment (P=0.83). CONCLUSIONS: Degree of aneurysm occlusion after the
      initial treatment is a strong predictor of the risk of subsequent rupture in
      patients presenting with subarachnoid hemorrhage, which justifies attempts to
      completely occlude aneurysms.

PMID- 18048861
TI  - Barriers to the use of anticoagulation for nonvalvular atrial fibrillation: a
      representative survey of Australian family physicians.
AB  - BACKGROUND AND PURPOSE: Anticoagulation reduces the risk of stroke in nonvalvular
      atrial fibrillation yet remains underused. We explored barriers to the use of
      anticoagulants among Australian family physicians. METHODS: The authors conducted
      a representative, national survey. RESULTS: Of the 596 (64.4%) eligible family
      physicians who participated, 15.8% reported having a patient with nonvalvular
      atrial fibrillation experience an intracranial hemorrhage with anticoagulation
      and 45.8% had a patient with known nonvalvular atrial fibrillation experience a
      stroke without anticoagulation. When presented with a patient at "very high risk"
      of stroke, only 45.6% of family physicians selected warfarin in the presence of a
      minor falls risk and 17.1% would anticoagulate if the patient had a treated
      peptic ulcer. Family physicians with less decisional conflict and longer-standing
      practices were more likely to endorse anticoagulation. CONCLUSIONS: Strategies to
      optimize the management of nonvalvular atrial fibrillation should address
      psychological barriers to using anticoagulation.

PMID- 18048862
TI  - Evolution of neurological, neuropsychological and sleep-wake disturbances after
      paramedian thalamic stroke.
AB  - BACKGROUND AND PURPOSE: The clinical features and natural course of paramedian
      thalamic stroke is poorly known. The aim of this study was to characterize the
      evolution of neurological, neuropsychological, and sleep-wake deficits after
      paramedian thalamic stroke. METHODS: Forty-six consecutive patients, aged 48.4+/
      16.6 years, were studied. Fourteen had bilateral, 16 left-sided, and 16 right
      sided lesions. Assessment included neurological examinations, estimation of sleep
      needs, formal neuropsychological tests (n=27), and polysomnographies (n=31).
      Functional outcome was followed up over 1 year in 31 patients with the modified
      Rankin Scale and Barthel index. RESULTS: Oculomotor palsy (76% of patients), mild
      gait ataxia (67%), deficits of attention (63%), fluency and error control (59%),
      learning and memory (67%), and behavior (67%) were common in the acute stroke
      phase. Outcome was excellent with right-sided infarcts but mostly incomplete with
      bilateral and left-sided lesions. This was mainly related to persistent frontal
      lobe-related and cognitive deficits found in 100% bilateral and 90% left-sided,
      but only 33% right-sided strokes. Initially, hypersomnia was present in all
      patients associated with increased stage 1 sleep, reduced stage 2 sleep, and
      reduced sleep spindles. Sleep needs improved in patients with bilateral and
      almost disappeared with unilateral lesions after 1 year. Sleep architecture
      remained abnormal with the exception of sleep spindles that increased.
      CONCLUSIONS: Whereas neurological deficits and hypersomnia recover to large
      extent in patients with paramedian thalamic stroke, the frontal lobe-related and
      cognitive deficits, which are mainly linked with bilateral and left-sided
      lesions, often persist. As such, stroke outcome is better in right-sided than
      bilateral or left-sided infarcts.

PMID- 18048863
TI  - Change in hemostatic markers after recombinant tissue-type plasminogen activator
      is not associated with the chance of recanalization.
AB  - BACKGROUND AND PURPOSE: We evaluated the association between recombinant tissue
      type plasminogen activator recanalization and change in hemostatic markers.
      METHODS: We studied 40 patients. Recanalization was measured with transcranial
      Doppler. We evaluated the change in markers of coagulation (fibrinogen) and
      fibrinolysis (thrombin activatable fibrinolysis inhibitor and alpha(2)
      antiplasmin) in patients with ischemic stroke treated with recombinant tissue
      type plasminogen activator. Samples were obtained before and 90 minutes after
      recombinant tissue-type plasminogen activator infusion. RESULTS: The analyses (2
      way analysis of variance) showed that the change in the value of each marker did
      not depend on the vascular patency status. CONCLUSIONS: From a practical point of
      view, the measurement of these hemostatic markers is probably not useful for
      predicting recanalization.

PMID- 18048864
TI  - Analysis of lymphocyte subsets in patients with stroke and their influence on
      infection after stroke.
AB  - BACKGROUND AND PURPOSE: Recent studies have attributed the increased infection
      vulnerability of patients with stroke to stroke-induced immunosuppression. We
      have therefore explored the immunological changes in patients with ischemic
      stroke. METHODS: Blood from 46 patients with stroke was analyzed by fluorescent
      activated cell sorter to determine leukocyte subsets. To identify changes that
      represent clinically relevant immunosuppression, we compared patients who
      developed infection within 14 days after stroke with those who did not. RESULTS:
      Stroke induced a dramatic and immediate loss of T-lymphocytes, most pronounced
      within 12 hours after stroke onset. Only patients with subsequent infection
      exhibited a delay in the recovery of CD4+ T-lymphocyte counts. CONCLUSIONS: Our
      data suggest that a loss of CD4+ T cell function contributes to the stroke
      induced immunosuppression. The CD4+ T cell count on the day after stroke may
      emerge as a predictive marker for poststroke infection allowing, early
      identification of patients at risk.

PMID- 18048865
TI  - Kidney function is related to cerebral small vessel disease.
AB  - BACKGROUND AND PURPOSE: Poor kidney function, as measured by glomerular
      filtration rate (GFR), is closely associated with presence of glomerular small
      vessel disease. Given the hemodynamic similarities between the vascular beds of
      the kidney and the brain, we hypothesized an association between kidney function
      and markers of cerebral small vessel disease on MRI. We investigated this
      association in a population-based study of elderly persons. METHODS: We measured
      GFR using the Cockcroft-Gault equation in 484 participants (60 to 90 years of
      age) from the Rotterdam Scan Study. Using automated MRI-analysis we measured
      global as well as lobar and deep volumes of gray matter and white matter, and
      volume of WML. Lacunar infarcts were rated visually. Volumes of deep white matter
      and WML and presence of lacunar infarcts reflected cerebral small vessel disease.
      We used linear and logistic regression models to investigate the association
      between GFR and brain imaging parameters. Analyses were adjusted for age, sex,
      and additionally for cardiovascular risk factors. RESULTS: Persons with lower GFR
      had less deep white matter volume (difference in standardized volume per SD
      decrease in GFR: -0.15 [95% CI -0.26 to -0.04]), more WML (difference per SD
      decrease in GFR: 0.14 [95% CI 0.03 to 0.25]), and more often lacunar infarcts,
      although the latter was not significant. GFR was not associated with gray matter
      volume or lobar white matter volume. Additional adjustment for cardiovascular
      risk factors yielded similar results. CONCLUSIONS: Impaired kidney function is
      associated with markers of cerebral small vessel disease as assessed on MRI.

PMID- 18048866
TI  - The 2007 Feinberg lecture: a new road map for neuroprotection.
AB  - BACKGROUND AND PURPOSE: There have now been numerous phase III trials of
      neuroprotection that have failed to live up to the expectations created by
      preclinical testing in animal models, the most recent of which was the second
      pivotal trial of the spin trap agent NXY-059. We have reached a stage at which
      research in this area should stop altogether or radical new approaches adopted.
      The purpose of this article is to review how we reached this stage and make
      recommendations for a new approach to neuroprotection research. METHODS: The
      background to neuroprotection research is reviewed and its problems are
      highlighted based on the research of others and of our own research group. From
      this, a series of questions are posed that require answers if the field is to
      progress. A road map for future research is then proposed. RESULTS: The road map
      involves the following steps for putative neuroprotectants: (1) better proof of
      efficacy in animal models; (2) in vivo evidence of efficacy in human tissue using
      cell cultures or brain slices; (3) in vivo studies of their distribution in the
      normal and ischemic human brain, particularly focusing on the ischemic penumbra;
      (4) demonstration of efficacy in novel human models of cerebral ischemia; and (5)
      phase II and III clinical trails with penumbral selection using imaging
      techniques. CONCLUSIONS: The accumulated evidence suggests that neuroprotection
      failure in clinical trial is due to identifiable preclinical and clinical
      factors. Neuroprotection research should be pursued but with a very different and
      more rigorous approach.

PMID- 18048867
TI  - Wound healing and global action on poverty and development.

PMID- 18048868
TI  - The significance of measurements in wound healing: where do we go from here?

PMID- 18048869
TI  - Digital imaging of wounds: are measurements reproducible among observers?
AB  - Advances in digital imaging and archiving have made the measurement and
      documentation of wound areas possible over time. To assess the reproducibility
      and precision of digital image measurements, we used WoundMatrix Web
      (http://www.woundmatrix.com/) and recruited a group of caregivers from the Johns
      Hopkins Wound Center to measure the size of wounds on digital images by measuring
      length and width and tracing the circumference of the same wounds. One set of
      images was provided by WoundMatrix (WoundMatrix Inc, Chadds Ford, PA) and a
      second set used our own photographs taken at the Johns Hopkins Wound Center. Our
      results demonstrate that digital analysis with WoundMatrix Web is reproducible
      and precise with acceptable variation among readers. This supports the use of
      digital images of wounds to follow clinical progress as well as analyze the
      effects of new clinical interventions in clinical trials.

PMID- 18048870
TI  - A critical analysis of measurements used to assess and manage scars.
AB  - Scars evolve through a maturation stage during which it is necessary to adapt
      different treatments. To adapt treatments, it is necessary to assess various
      parameters linked to inflammation. To this end, clinical scar assessments are
      subjective though reliable, and validation is operator dependent. The Vancouver
      Scar Scale, Visual Analogic Scale, Patient and Observer Scar Assessment Scale,
      and the Manchester Scale assess different scar characteristics. These scales are
      interesting, depending on the type of scars, and are easy to use but subject to
      errors. To use clinical a scale, the raters must be trained. Parameters can also
      be precisely assessed by technical means, whereby they rate only one parameter,
      but are more accurate. Some scales are easy to use, have low cost, and can be
      used for clinical assessment. Others scales are more complex and expensive, and
      can be used in research or treatment evaluation.

PMID- 18048871
TI  - The role of hemodynamic measurements in the management of venous and ischemic
      ulcers.
AB  - There is a need for quantitative investigations in the vascular laboratory to
      manage lower extremity ulcers. The majority of leg ulcers are of venous (45%-60%)
      or arterial origin (10%-20%). Despite the increasing complexity of new devices
      used in vascular surgical practice, the anklebrachial pressure index (ABPI)
      remains the cornerstone for the differential diagnosis of ischemic ulcers. The
      toe-brachial pressure index and the pole test represent attractive alternative
      tests especially in patients with diabetes. Color flow Doppler imaging (CFDI) is
      advantageous over ABPI in cases in which wounds and ulcers prevent the use of a
      cuff by virtue of their size or location; additionally CFDI technology can detect
      nonflow limiting lesions, lesions to nonaxial arteries such as the deep femoral
      artery, or lesions limited to a single tibial artery. Continued improvements in
      the accuracy of CFDI have prompted some vascular surgeons to replace contrast
      arteriography in distal bypass procedures. Transcutaneous partial oxygen tension
      measurement (TcPO(2)) is another noninvasive method that is reliable to select
      the level of amputation and recommended to determine tissue viability in
      critically ischemic limbs and in the management of the diabetic foot. CFDI has
      revolutionized the diagnostic approach to venous disorders and it is considered
      the gold standard for the assessment of the venous system of the lower limb,
      causes minimal inconvenience to patients, and is easily repeatable, but it is
      considered highly operator dependent. Various plethysmography techniques are of
      limited application in ulcer investigations, because of their difficulty to
      calibrate signal, unless time measurements such as the postexercise refilling
      time are used.

PMID- 18048872
TI  - Wound fluids: a window into the wound environment?
AB  - Wound healing of the skin is a complex biologic process involving temporal
      interactions between numerous types of cells, extracellular matrix molecules, and
      soluble factors. The process of repair can be viewed as involving 3 or 4 phases:
      homeostasis, inflammation, synthesis, and remodeling. These phases occur at
      different times and differ in their cellular, biochemical, and physiologic
      requirements. Disruption of one or more of these interactions can significantly
      interfere with the repair process. Such comorbidities as age, nutrition, immune
      status, and underlying disease status (eg, diabetes or venous stasis) contribute
      additional intricacy to the repair process. Because of this complexity, care of
      chronic wounds remains highly individualized, and it should not come as a
      surprise that treatment of these wounds as a group with single target therapies
      have met with only modest success. A major hurdle in the progression toward
      improved treatment regimens has been the lack of objective biochemical and
      physiological landmarks that can be used to assess wound status. Collection and
      biochemical characterization of wound fluids presents the opportunity to
      noninvasively obtain information reflecting the status of the wound and of
      specific biomarkers. This review discusses the collection of wound fluid and
      highlights biomarkers that may be useful to this end.

PMID- 18048873
TI  - A review of the clinical significance of tissue hypoxia measurements in lower
      extremity wound management.
AB  - The aim of this paper is to review techniques that are currently available to
      measure tissue hypoxia in order to benefit the management of wounds. Direct
      measurement of tissue partial oxygen pressure (PO(2)) is invasive and therefore
      unappealing in clinical practice. Several techniques (PET scans, MRI derived
      techniques) are primarily applicable to research rather than clinical
      applications. Imaging techniques (duplex ultrasonography, arteriography, MRI
      techniques) are recommended only as part of the workup for revascularisation.
      Techniques that assess local perfusion include clearance methods, transcutaneous
      O(2) and CO( 2) pressure measurement, and laser Doppler flowmetry and imaging.
      These techniques permit interpretation of altered perfusion states. Each
      technique offers subtly different information concerning microvascular function.
      All these techniques require strict protocols to derive reliable data. The
      potential of the promising near infrared reflectance spectroscopy (NIRS)
      technique is yet to be determined.

PMID- 18048874
TI  - Outcome measurements in wound healing are not inclusive: a way forward.
AB  - Standardized outcome measurement in wound healing has been an elusive goal.
      Whilst research into wound healing science and technology continues to progress
      rapidly, the lack of a uniform outcome assessment is making comparative analysis
      of results difficult. This paper seeks to outline the reported clinical,
      physiological, and histological outcomes that have been utilized in the
      literature. A minimal data set base for wound outcome evaluation is also
      established to be validated by future multivariate analysis of patient data.

PMID- 18048875
TI  - Disabling pansclerotic morphea of childhood poses a high risk of chronic
      ulceration of the skin and squamous cell carcinoma.
AB  - Disabling pansclerotic morphea of childhood (DPMC) is a rare and severe variant
      of scleroderma. This report presents 3 cases that presented to the authors and
      studies 25 patients from the literature (English language only) for the presence
      of chronic nonhealing ulcers of skin and skin cancer. The authors identified a
      total of 30 patients (9 male and 21 female) aged between 1 and 37 years at time
      of presentation. All cases were less than 14 years old when the disease started.
      The majority of patients had an aggressive course with deep sclerotic lesions
      leading to joint contractures and immobility. Five patients suffered from chronic
      nonhealing leg ulcers (17%), but ulcers were present on other parts of the body
      (upper limbs, trunk, head) as well (n = 6). Four patients died because of
      complications of the disease such as sepsis or gangrene. Two patients developed a
      squamous cell carcinoma at the age of 16 years and 19 years, respectively (6.7%).
      The available treatment of DMPC-associated ulcers is unsatisfying. Only temporary
      improvements have been seen in a minority of patients. We report on marked
      improvement of chronic leg ulcers by a combination of sildenafil 3 x 20 mg/day
      and repeated application of a porcine small intestinal submucosal acellular
      matrix.

PMID- 18048876
TI  - Treatment of acute seizures and status epilepticus.
AB  - Overt status epilepticus and persistent obtundation after a witnessed clinical
      seizure are neurologic emergencies. Early recognition and intervention in the
      electroclinical syndrome of status epilepticus reduces morbidity, although
      treatment of the underlying etiology is also critical. This review outlines key
      concepts related to status epilepticus, delineates an approach to the early
      management of status epilepticus, and highlights novel but practical approaches
      in the evaluation and treatment of refractory status epilepticus, emphasizing the
      use of a treatment algorithm. This review is written from the perspective of the
      intensive care unit clinician, and the approach and opinions expressed stem from
      clinical experience and review of the current literature. Particular attention is
      given to an overall approach to the management of convulsive status epilepticus
      in adults and older children as well as exploring novel approaches and diagnostic
      tools that may prove useful in difficult-to-control status epilepticus.

PMID- 18048877
TI  - Adrenal insufficiency in critical illness.
AB  - One of the more controversial areas in critical care in recent decades relates to
      the issue of adrenal insufficiency and its treatment in critically ill patients.
      There is no consensus on which patients to test for adrenal insufficiency, which
      tests to use and how to interpret them, whether to use corticosteroids, and, if
      so, who to treat and with what dose. This review illustrates the complexity and
      diversity of pathophysiological changes in glucocorticoid secretion, metabolism,
      and action and how these are affected by various types of illness. It will review
      adrenal function testing and give guidance on corticosteroid replacement regimens
      based on current published literature. There remain inherent difficulties in
      interpreting the effects of glucocorticoid replacement during critical illness
      because of the diversity of effects of glucocorticoids on various tissues.
      Investigation and treatment will depend on whether the likely cause of
      corticosteroid insufficiency is adrenal or central in origin.

PMID- 18048878
TI  - Implementation of a handheld electronic point-of-care billing system improved
      efficiency in the critical care unit.
AB  - Coding and billing are time consuming and important considerations for critical
      care practitioners. A 1-year prospective, observational study incorporated the
      use of a personal digital assistant and MDeverywhere software (Hauppauge, New
      York) for patient coding and billing. Twelve months of data were examined before
      electronic implementation (pre-elec) and compared with a 12-month period after
      implementation (post-elec) by using an unpaired t test or z test with P < .05
      considered significant. The total number of charges was 2479 pre-elec and 2243
      post-elec. The days from date of service to billing for services significantly
      decreased from 37.8 pre-elec to 12.4 post-elec (P < .001); days in accounts
      receivable significantly decreased from 92.0 to 73.0 (P < .001). The net
      collection rate increased from 44.7% pre-elec to 49.3% post-elec (P < .001).
      Duplicate charges significantly decreased from 5.0% pre-elec to 1.4% post-elec (
      P < .001). The return on investment was 1.97-fold (197%). The initiation of
      personal digital assistant technology to facilitate billing and coding resulted
      in significant improvements.

PMID- 18048879
TI  - B-type natriuretic peptide and sepsis: it is not just the heart.

PMID- 18048880
TI  - On models for integrative medical practice.

PMID- 18048881
TI  - Lesson from comparison of CAM use by women with female-specific cancers to
      others: it's time to focus on interaction risks with CAM therapies.
AB  - There has been no examination as to whether the prevalence of complementary and
      alternative medicine (CAM) use, as well as personal factors associated with CAM
      use and predictive of CAM use for women with female-specific cancers, is similar
      to those in other diagnostic groups. The purpose of this review is to compare CAM
      use and personal factors associated with and predictive of CAM use by women with
      female-specific cancers to samples of other diagnostic groups. If it is the case
      that CAM use is similar across various types of samples, then it may be
      unnecessary to continue to study detailed CAM use by those in separate diagnostic
      groups and instead focus energies on the examination of CAM therapies that may
      have risks for interaction with conventional therapies, such as biologically
      based therapies. The researcher concludes that we are now in an era in which we
      need to use our restricted time, human resources, and finances to examine
      biologically based CAM use that may carry high risks for interactions or
      toxicities for specific groups under examination, rather than examine global CAM
      use, unless the situation warrants such all-inclusive study.

PMID- 18048882
TI  - Assessing the role of evidence in patients' evaluation of complementary
      therapies: a quality study.
AB  - BACKGROUND: Making the decision to use complementary and alternative medicine
      (CAM) for cancer treatment is difficult in light of the limited available
      evidence for these treatments. It is unclear how patients use evidence to make
      these decisions. OBJECTIVES: (1) Describe the type of information about CAM that
      cancer patients use in their decision making; (2) understand why certain types of
      information about CAM are accepted as evidence by cancer patients; and (3)
      explore the role of scientific evidence in treatment decision making. METHODS: A
      qualitative study design using in-depth semistructured interviews with cancer
      patients attending 4 conventional and integrative health care institutions in
      Alberta and British Columbia, Canada, was used. RESULTS: Twenty-seven patients
      were interviewed. Patients sought CAM information from a range of sources,
      including the Internet, health care providers, friends, relatives, and
      newspapers. Many expressed frustration about the overwhelming amount of available
      information and found it difficult to identify reliable information. Information
      was described as reliable if it supported them in arriving at a decision about
      CAM. Types of information participants identified included anecdotes, expert
      opinion, gut feeling, popular literature, scientific evidence, testimonials,
      advertising and trial and error. Profound differences were found between new CAM
      users, experienced CAM users, and users with late-stage cancer in type of
      information sought, the role of scientific evidence in decision making, and
      overall information needs. CONCLUSION: Although this was a relatively small
      qualitative study, the results suggest that (1) many patients do not value
      scientific evidence as highly as conventional providers and (2) it is important
      for clinicians and other information providers to be aware of the different types
      of information that patients seek out and access when making choices and
      decisions regarding CAM treatments and why they seek out these sources.

PMID- 18048883
TI  - Autophagic cell death of human pancreatic tumor cells mediated by oleandrin, a
      lipid-soluble cardiac glycoside.
AB  - Lipid-soluble cardiac glycosides such as bufalin, oleandrin, and digitoxin have
      been suggested as potent agents that might be useful as anticancer agents. Past
      research with oleandrin, a principle cardiac glycoside in Nerium oleander L.
      (Apocynaceae), has been shown to induce cell death through induction of
      apoptosis. In PANC-1 cells, a human pancreatic cancer cell line, cell death
      occurs not through apoptosis but rather through autophagy. Oleandrin at low
      nanomolar concentrations potently inhibited cell proliferation associated with
      induction of a profound G(2)/M cell cycle arrest. Inhibition of cell cycle was
      not accompanied by any significant sub G1 accumulation of cells, suggesting a
      nonapoptotic mechanism. Oleandrin-treated cells exhibited time- and concentration
      dependent staining with acridine orange, a lysosomal stain. Subcellular changes
      within PANC-1 cells included mitochondrial condensation and translocation to a
      perinuclear position accompanied by vacuoles. Use of a fluorescent oleandrin
      analog (BODIPY-oleandrin) revealed co-localization of the drug within cell
      mitochondria. Damaged mitochondria were found within autophagosome structures.
      Formation of autophagosomes was confirmed through electron microscopy and
      detection of green fluorescent protein-labeled light chain 3 association with
      autophagosome membranes. Also observed was a drug-mediated inhibition of pAkt
      formation and up-regulation of pERK. Transfection of Akt into PANC-1 cells or
      inhibition of pERK activation by MAPK inhibitor abrogated oleandrin-mediated
      inhibition of cell growth, suggesting that the reduction of pAkt and increased
      pERK are important to oleandrin's ability to inhibit tumor cell proliferation.
      The data provide insight into the mechanisms and role of a potent, lipid-soluble
      cardiac glycoside (oleandrin) in control of human pancreatic cancer
      proliferation.

PMID- 18048884
TI  - Lipid peroxidation, total antioxidant status, and total thiol levels predict
      overall survival in patients with oral squamous cell carcinoma.
AB  - Tobacco is the major etiological factor for oral cancer development through the
      generation of oxidative stress. Therefore, markers of oxidative stress such as
      total antioxidant status, lipid peroxidation, and total thiol levels might be
      useful to monitor oxidative stress and predict overall survival in oral cancer
      patients. The study included 140 oral cancer patients and 50 healthy controls,
      who were classified as with the habit of tobacco and no habit of tobacco.
      Adjacent normal and malignant tissue samples were collected from oral cancer
      patients. Plasma and tissue levels of lipid peroxidation, thiol, and total
      antioxidant status were assayed by spectrophotometric methods. Thiol levels were
      significantly lower in controls with the habit of tobacco (P= .033), oral cancer
      patients (P= .0001), and malignant tissues (P= .015) as compared to controls with
      no habit of tobacco, controls with the habit of tobacco, and adjacent normal
      tissues, respectively. Tobacco exposure was higher in oral cancer patients than
      controls with the habit of tobacco. Controls with the habit of tobacco who had
      lower thiol (odds ratio [OR]=10.58, P= .008) and high tobacco exposure (OR=0.251,
      P= .05) showed an elevated risk of oral cancer development. Patients showing a
      lipid peroxidation level above the cutoff level as compared to patients below the
      cutoff level showed poor overall survival, whereas those with thiol and total
      antioxidant status levels below the cutoff level as compared to their respective
      counterparts showed poor overall survival. In conclusion, lipid peroxidation and
      thiol could be useful for predicting the risk of oral carcinogenesis in healthy
      tobacco consumers and predicting overall survival of oral cancer patients.

PMID- 18048885
TI  - Apoptotic effect of Biophytum sensitivum on B16F-10 cells and its regulatory
      effects on nitric oxide and cytokine production on tumor-associated macrophages.
AB  - The present study is part of a large-scale investigation of the antitumor effects
      of Biophytum sensitivum on B16F-10 melanoma cells. The investigation involved the
      regulatory effect of B sensitivum on nitric oxide and cytokine production in B16F
      10 cells, tumor-associated macrophages, and peritoneal macrophages as well as on
      the apoptotic process in B16F-10 melanoma cells. B sensitivum at a concentration
      of 10 microg/mL could significantly (P< .001) inhibit production of nitric oxide
      and proinflammatory cytokines such as interleukin-1beta, interleukin-6,
      granulocyte monocyte-colony stimulating factor, and tumor necrosis factor-alpha
      in B16F-10 cells, tumor-associated macrophages, and peritoneal macrophages.
      Incubation of B16F-10 cells with B sensitivum showed the presence of apoptotic
      bodies and induced DNA fragmentation. Furthermore, B sensitivum showed an
      inhibitory effect on inducible nitric oxide synthase as well as bcl-2 expression,
      and up-regulated p53 and caspase-3 messenger RNA expression in B16F-10 melanoma
      cells. The observed results suggest that regulation of proinflammatory cytokine
      production by tumor cells, tumor-associated macrophages, and resident macrophages
      accompanied by altered inducible nitric oxide synthase, bcl-2, caspase-3, and p53
      messenger RNA expression by B sensitivum methanol extract induces apoptosis in
      B16F-10 melanoma cells.

PMID- 18048886
TI  - Studies on the protective effects of Boerhaavia diffusa L. against gamma
      radiation induced damage in mice.
AB  - The radioprotective effect of the hydro-alcoholic extract of Boerhaavia diffusa
      was studied using the in vivo mice model. The sublethally irradiated mice (600
      rads, single dose) were treated intraperitoneally with 20 mg/kg of the extract.
      The animals were sacrificed at different time periods after the whole-body
      radiation. The most affected tissues--bone marrow and intestine--were
      considerably protected by the intraperitoneal administration of B. diffusa as
      estimated by bone marrow cellularity, maturing monocytes, and intestinal
      glutathione. Total white blood cell count was lowered drastically after radiation
      exposure (ninth day, 1500+/-500 cells/ mm(3)). When the animals were exposed to
      radiation and treated with B. diffusa, the total white blood cell count was
      lowered only to 4000+/-400 cells/mm(3) on the third day, and it reached an almost
      normal level (6250+/-470 cells/mm(3)) by the ninth day. The elevated level of
      serum and liver alkaline phosphatase after radiation exposure was reduced in the
      B. diffusa-treated group. The serum and liver glutamate pyruvate transferase,
      which were elevated after radiation exposure, were also reduced by treatment with
      B. diffusa compared to the control. The lipid peroxidation level also increased
      in the irradiated animals both in the liver and serum, but in B. diffusa-treated
      animals, there was a significant reduction in lipid peroxidation levels. The
      agarose gel electrophoresis of DNA isolated from bone marrow of mice exposed to
      gamma radiation showed heavy damage that was reduced by treatment with B.
      diffusa. These results are indicative of the radioprotective effect of the whole
      plant extract of B. diffusa.

PMID- 18048887
TI  - Inhibition of endothelial cell differentiation and proinflammatory cytokine
      production during angiogenesis by allyl isothiocyanate and phenyl isothiocyanate.
AB  - Angiogenesis is a crucial step in the growth and metastasis of cancers. The
      activation of endothelial cells and their further behavior are very critical
      during angiogenesis. The authors analyze the effect of allyl isothiocyanate
      (AITC) and phenyl isothiocyanate (PITC) on angiogenesis in an in vitro model
      using human umbilical vein endothelial cells (HUVECs). AITC and PITC
      significantly inhibited endothelial cell migration, invasion, and tube formation.
      (3)H-thymidine proliferation assay showed that AITC and PITC significantly
      inhibited the proliferation of HUVECs in vitro. The authors also studied the
      effect of AITC and PITC on the serum cytokine profiles of angiogenesis-induced
      animals and found that these compounds are highly potent in the downregulation of
      vascular endothelial growth factor (VEGF) and proinflammatory cytokines such as
      interleukin (IL)-1beta , IL-6, granulocyte macrophage colony-stimulating factor
      (GM-CSF), and tumor necrosis factor alpha (TNF-alpha). Treatment with these
      compounds showed an elevation in the levels of IL-2 and tissue inhibitor of
      metalloproteinases (TIMP)-1, which are antiangiogenic factors. Moreover, studies
      using B16F-10 melanoma cells showed that both AITC and PITC significantly reduced
      VEGF mRNA expression. These findings suggest that AITC and PITC act as
      angiogenesis inhibitors through the downregulation of VEGF and proinflammatory
      cytokines such as IL-1beta, IL-6, GM-CSF, and TNF-alpha and upregulation of IL-2
      and TIMP.

PMID- 18048888
TI  - Chinese herbs of Shenghe Powder reverse multidrug resistance of gastric carcinoma
      SGC-7901.
AB  - The objective of this study was to investigate the reversal effect of Chinese
      herbs of Shenghe Powder on the multidrug resistance of the human SGC-7901 gastric
      carcinoma cell line and vincristine-resistant cell line (SGC-7901/vincristine)
      and the possible mechanism. SGC-7901 and SGC-7901/ vincristine were cultured in
      liquid medium RMPI 1640, with the addition of vincristine to the vincristine
      resistant line. The reversal effect of Shenghe Powder (using verapamil as
      control) on the multidrug resistance of SGC-7901/vincristine cells was observed
      using the 3-4,5-dimethylthiazol-2yl) -2,5-diphenylterazolium bromide method. The
      expression rate of P-glycoprotein (P-gp), lymphoma/leukemia-2 (Bcl-2), and
      apoptosis ratio of SGC-7901 and SGC-7901/vincristine with added Shenghe Powder,
      verapamil, or verapamil plus Shenghe Powder was observed by flow cytometry.
      Shenghe Powder and verapamil decreased the multidrug resistance of SGC
      7901/vincristine. The effect of Shenghe Powder (10 mg/L) was significantly higher
      than verapamil (P< .05). The intracellular concentration of vincristine was
      increased by Shenghe Powder and verapamil. The vincristine concentration of SGC
      7901/vincristine treated with Shenghe Powder was significantly higher (P< .05).
      Shenghe Powder reduced the expression level of P-gp and Bcl-2 in SGC-7901/
      vincristine and increased the apoptotic percentage of tumor cells; Shenghe Powder
      had the more significant effect on apoptosis (P< .05). In conclusion, Shenghe
      Powder increases the intracellular concentration of vincristine, consistent with
      the down-regulation of the expression of P-gp and Bcl-2. The reversal effect of
      Shenghe Powder was stronger than that of verapamil.

PMID- 18048889
TI  - Chemopreventive potential of Aloe vera against 7,12-dimethylbenz(a)anthracene
      induced skin papillomagenesis in mice.
AB  - The present investigation was undertaken to explore the antitumor-promoting
      activity of Aloe vera on 2-stage skin carcinogenesis, induced by a single topical
      application of 7,12-dimethylbenz(a)anthracene and promoted by treatment of croton
      oil for 16 weeks in Swiss albino mice. Oral administration of aloe leaf extract
      at a dose of 1000 mg/kg body weight/d and aloe gel treatment at a dose of 1 mL/9
      cm(2)/mice/d was found to be effective in decreasing the number and size of the
      papillomas. A significant reduction in tumor incidence (40.00+/-5.10, 30.00+/
      3.25, and 40.00+/-4.12 for aloe gel, aloe gel and aloe leaf extract combined, and
      aloe leaf extract alone, respectively) was observed in animals in the aloe
      extract- and aloe gel-treated groups compared with 100% tumor incidence in the
      control group. The cumulative number of papillomas during an observation period
      of 16 weeks was significantly reduced in the aloe-treated groups (8.0+/-0.34,
      6.00+/-1.10, and 9.00+/-1.41 for aloe gel, aloe gel and leaf extract, and aloe
      leaf extract, respectively) compared with a 36+/-0.98 cumulative number of
      papillomas in the control group. The average latent period was significantly
      increased from 4.9+/-0.10 weeks in the control group to 6.37+/-0.12, 6.8+/-0.25,
      and 6.2+/-0.21 weeks in the aloe-treated groups, respectively. The tumor burden
      and tumor yield were significantly decreased (2.0+/-0.25, 2.00+/-0.30, and 2.25+/
      0.2 and 0.8+/-0.25, 0.6+/-0.32, and 0.9+/-0.28, respectively) as compared with
      the 7,12-dimethylbenz(a)anthracene-treated control group (3.6+/-0.10 and 3.6+/
      0.19). Furthermore, treatment with aloe gel and/or extract by topical and/or oral
      administration resulted in a significant increase in the reduced glutathione (P<
      .05), DNA (P< .001), catalase (P< .05), and protein (P< .001) in the skin of
      mice. Conversely, lipid peroxidation levels were significantly decreased (P<
      .001) in the skin of mice.

PMID- 18048890
TI  - Takuo Aoyagi: discovery of pulse oximetry.
AB  - In the 1930s and 1940s, photo cells permitted German, English, and American
      physiologists to construct ear oximeters with red and infrared light, requiring
      calibration. In 1940 Squire recognized that changes of red and infrared light
      transmission caused by pneumatic tissue compression permitted saturation to be
      computed. In 1949 Wood used this idea to compute absolute saturation continuously
      from the ratios of optical density changes with pressure in an ear oximeter. In
      1972 Takuo Aoyagi, an electrical engineer at Nihon Kohden company in Tokyo, was
      interested in measuring cardiac output noninvasively by the dye dilution method
      using a commercially available ear oximeter. He balanced the red and infrared
      signals to cancel the pulse noise which prevented measuring the dye washout
      accurately. He discovered that changes of oxygen saturation voided his pulse
      cancellation. He then realized that these pulsatile changes could be used to
      compute saturation from the ratio of ratios of pulse changes in the red and
      infrared. His ideas, equations and instrument were adapted, improved and
      successfully marketed by Minolta about 1978, stimulating other firms to further
      improve and market pulse oximeters worldwide in the mid 1980s. Dr. Aoyagi and
      associates provided a detailed history for this paper.

PMID- 18048891
TI  - The light-tissue interaction of pulse oximetry.
AB  - The underlying science of pulse oximetry is based on a simple manipulation of the
      Lambert-Beer law, which describes the attenuation of light traveling through a
      mixture of absorbers. Signals from detected red and infrared light that has
      traveled through blood-perfused tissues are used to estimate the underlying
      arterial hemoglobin oxygen saturation. However, light scatters in tissue and
      influences some of the simplifications made in determining this relationship.
      Under most clinical circumstances, the empirical process that manufacturers use
      to calibrate the system during its design readily accommodates this and results
      in accurate readings. The same tissue light scattering properties allow sensors
      to be configured for use on opposing or adjacent surfaces, provided that the
      placement sites offer sufficient signal strength and are absent factors known to
      influence accuracy. In this paper I review the light-tissue interaction in pulse
      oximetry and describe some of the assumptions made and their implications.
      Certain deviations from the nominal conditions, whether clinical in nature or
      misuse of the product, can affect system performance. Consequently, users should
      be cautious in modifying sensors and/or using them on tissue sites not intended
      by the manufacturer (off-label use). While perhaps helpful for obtaining
      pulsatile signals or extending the lifetime of a sensor, some practices can
      disrupt the optical integrity of the measurement and negatively impact the oxygen
      saturation reading accuracy.

PMID- 18048893
TI  - Dark skin decreases the accuracy of pulse oximeters at low oxygen saturation: the
      effects of oximeter probe type and gender.
AB  - INTRODUCTION: Pulse oximetry may overestimate arterial oxyhemoglobin saturation
      (Sao2) at low Sao2 levels in individuals with darkly pigmented skin, but other
      factors, such as gender and oximeter probe type, remain less studied. METHODS: We
      studied the relationship between skin pigment and oximeter accuracy in 36
      subjects (19 males, 17 females) of a range of skin tones. Clip-on type sensors
      and adhesive/disposable finger probes for the Masimo Radical, Nellcor N-595, and
      Nonin 9700 were studied. Semisupine subjects breathed air-nitrogen-CO2 mixtures
      via a mouthpiece to rapidly achieve 2- to 3-min stable plateaus of Sao2.
      Comparisons of Sao2 measured by pulse oximetry (Spo2) with Sao2 (by Radiometer
      OSM-3) were used in a multivariate model to assess the source of errors. RESULTS:
      The mean bias (Spo2 - Sao2) for the 70%-80% saturation range was 2.61% for the
      Masimo Radical with clip-on sensor, -1.58% for the Radical with disposable
      sensor, 2.59% for the Nellcor clip, 3.6% for the Nellcor disposable, -0.60% for
      the Nonin clip, and 2.43% for the Nonin disposable. Dark skin increased bias at
      low Sao2; greater bias was seen with adhesive/disposable sensors than with the
      clip-on types. Up to 10% differences in saturation estimates were found among
      different instruments in dark-skinned subjects at low Sao2. CONCLUSIONS:
      Multivariate analysis indicated that Sao2 level, sensor type, skin color, and
      gender were predictive of errors in Spo2 estimates at low Sao2 levels. The data
      suggest that clinically important bias should be considered when monitoring
      patients with saturations below 80%, especially those with darkly pigmented skin;
      but further study is needed to confirm these observations in the relevant
      populations.

PMID- 18048894
TI  - Hemoximetry as the "gold standard"? Error assessment based on differences among
      identical blood gas analyzer devices of five manufacturers.
AB  - BACKGROUND: The calibration and testing procedures of a pulse oximeter with
      arterial blood samples from healthy subjects are based on reference values from
      the hemoximeter. There are no tests to identify the accuracy of the reference
      devices. Because of this limitation and since the true values of oxygen
      saturation (sO2 in %) in blood samples were not known, we used the differences
      between two identical devices, A and B, for error assessment. METHODS: Two
      identical devices, A and B, from five leading manufacturers were investigated.
      Seventy-two arterial blood samples from 12 healthy volunteers at three different
      levels of saturation between 100% and 70% sO2 were randomly evaluated by the test
      systems. RESULTS: The observed differences (Delta) between Devices A and B, as a
      measure for the error of the hemoximeters, increased significantly with all
      manufacturers from level 97 (Deltamin, -0.9%; Deltamax, 2.6%) to 85 (Deltamin, 
      2.4%; Deltamax, 4.3), this effect was even stronger between levels 97 and 75
      (Deltamin, -4.6%; Deltamax, 4.3%). A variance proportion analysis revealed the
      concentration of the reduced hemoglobin as the main error source for sO2
      measurements. Independent from the sO2 levels there were also significant
      differences for the carboxy hemoglobin concentration in the range of 0%-4% and
      for the methemoglobin concentration in the range of 0%-1%. CONCLUSIONS: The
      variance of sO2 measurements between identical devices increased significantly
      when saturation decreased from the normal level of 97% to the hypoxemic levels of
      85% and 75%.

PMID- 18048895
TI  - Photoplethysmography: beyond the calculation of arterial oxygen saturation and
      heart rate.
AB  - In this article, I examine the source of the photoplethysmograph (PPG), as well
      as methods of investigation, with an emphasize on amplitude, rhythm, and pulse
      analysis. The PPG waveform was first described in the 1930s. Although considered
      an interesting ancillary monitor, the "pulse waveform" never underwent intensive
      investigation. Its importance in clinical medicine was greatly increased with the
      introduction of the pulse oximeter into routine clinical care in the 1980s. Its
      waveform is now commonly displayed in the clinical setting. Active research
      efforts are beginning to demonstrate a utility beyond oxygen saturation and heart
      rate determination. Future trends are being heavily influenced by modern digital
      signal processing, which is allowing a re-examination of this ubiquitous
      waveform. Key to unlocking the potential of this waveform is an unfettered access
      to the raw signal, combined with standardization of its presentation, and methods
      of analysis. In the long run, we need to learn how to consistently quantify the
      characteristics of the PPG in such a way as to allow the results from research
      efforts be translated into clinically useful devices.

PMID- 18048896
TI  - Automated regulation of inspired oxygen in preterm infants: oxygenation stability
      and clinician workload.
AB  - Premature infants are at an increased risk of ophthalmic, neurologic, and
      respiratory sequelae related to inadequate maintenance of oxygenation and
      exposure to increased levels of inspired oxygen. Management of inspired oxygen is
      complicated in this population by an increased variability in oxygenation.
      Automated regulation of the fraction of inspired oxygen is a technology that has
      a potential of improving such outcomes as well as impacting personnel workload.
      This is a review of current experimental evidence on the effectiveness of
      automated regulation of inspired oxygen and its effects on oxygenation
      variability and personnel workload during the care of premature infants.

PMID- 18048897
TI  - Chip-scale sensor system integration for portable health monitoring.
AB  - The revolution in integrated circuits over the past 50 yr has produced
      inexpensive computing and communications systems that are powerful and portable.
      The technologies for these integrated chip-scale sensing systems, which will be
      miniature, lightweight, and portable, are emerging with the integration of
      sensors with electronics, optical systems, micromachines, microfluidics, and the
      integration of chemical and biological materials (soft/wet material integration
      with traditional dry/hard semiconductor materials). Hence, we stand at a
      threshold for health monitoring technology that promises to provide wearable
      biochemical sensing systems that are comfortable, inauspicious, wireless, and
      battery-operated, yet that continuously monitor health status, and can transmit
      compressed data signals at regular intervals, or alarm conditions immediately. In
      this paper, we explore recent results in chip-scale sensor integration technology
      for health monitoring. The development of inexpensive chip-scale biochemical
      optical sensors, such as microresonators, that are customizable for high
      sensitivity coupled with rapid prototyping will be discussed. Ground-breaking
      work in the integration of chip-scale optical systems to support these optical
      sensors will be highlighted, and the development of inexpensive Si complementary
      metal-oxide semiconductor circuitry (which makes up the vast majority of
      computational systems today) for signal processing and wireless communication
      with local receivers that lie directly on the chip-scale sensor head itself will
      be examined.

PMID- 18048898
TI  - The design, use, and results of transcutaneous carbon dioxide analysis: current
      and future directions.
AB  - Transcutaneous carbon dioxide (CO2) analysis was introduced in the early 1980s
      using locally heated electrochemical sensors that were applied to the skin
      surface. This methodology provides a continuous noninvasive estimation of the
      arterial CO2 value and can be used for assessing adequacy of ventilation. The
      technique is now established and used routinely in clinical practice.
      Transcutaneous partial pressure of CO2 (tcPco2) sensors are available as a single
      Pco2 sensor, as a combined Pco2/Po2 sensor, and more recently, as a combined
      Pco2/Spo2 sensor. CO2 is still measured potentiometrically by determining the pH
      of an electrolyte layer. The methodology has been continuously developed during
      the last 20 yr, making the tcPco2 systems easier and more reliable for use in
      clinical practice: smaller sensor size (diameter 15 mm, height 8 mm), less
      frequent sensor re-membraning (every 2 wk) and calibration (twice a day), sensor
      ready to use when connected to the monitor, lower sensor temperature (42 degrees
      C), shorter arterialization time (3 min), and increased measurement reliability
      through protection of the membrane. The present tcPco2 sensors still need to be
      regularly re-membraned and calibrated. One way to overcome these procedures is to
      use optical-only detection means. Two techniques have been developed using
      optical absorption in the near-infrared light, in the evanescent wave of a
      waveguide integrated in the sensor surface, or in a micro-optics sampling cell.
      Preliminary in vitro and in vivo CO2 measurements have been performed. The sensor
      is not affected by drift over several days, and its response time is <1 min.

PMID- 18048899
TI  - Misconceptions in reporting oxygen saturation.
AB  - BACKGROUND: We describe some misconceptions that have become common practice in
      reporting blood gas and cooximetry results. In 1980, oxygen saturation was
      incorrectly redefined in a report of a new instrument for analysis of hemoglobin
      (Hb) derivatives. Oxygen saturation (sO2) was redefined as the ratio of
      oxyhemoglobin (O2Hb) to total Hb instead of the ratio of O2Hb to active Hb (O2Hb
      + desoxyhemoglobin). In addition, the new terms "functional saturation" and
      "fractional saturation" were introduced. Since the new parameter was implemented
      in a widely used cooximeter, its use is now widespread and has caused
      misunderstandings. METHODS: In this report, we review the development of the
      definitions and measurements of sO2 and related quantities and contend that the
      misconceptions should be resolved by standardizing instrument read-outs and
      clinical reports, so that sO2, defined as the ratio of O2Hb to active Hb, should
      replace FO2Hb and be reported along with the total Hb concentration and the
      common dyshemoglobin fractions (%CO-Hb and % methemoglobin [metHb]). RESULTS: The
      redefinition of sO2 as the %O2Hb or FO2Hb did not address the confusion that
      might result from interchanging these two often-similar but different terms. The
      term fractional saturation is an inappropriate terminology and lacks clear
      physiological meaning. We see frequent cases of confusion: (a) the difference
      between the sO2 in pulse oximetry and the FO2Hb in cooximetry is called the
      "pulse oximeter gap;" (b) sO2 results are described as "method dependent;" and
      (c) reference ranges for these terms are substituted. CONCLUSIONS: Although
      either parameter could be used by clinicians who fully understand the relatively
      simple difference between these parameters, we find clear evidence that there is
      widespread confusion of these terms, even among experts in the field.
      Standardization of the reporting format would help, and instrument manufacturers
      could contribute by standardizing the reporting format for cooximetry results.

PMID- 18048900
TI  - Multiwavelength pulse oximetry: theory for the future.
AB  - BACKGROUND: As the use of pulse oximeters increases, the needs for higher
      performance and wider applicability of pulse oximetry have increased. To realize
      the full potential of pulse oximetry, it is indispensable to increase the number
      of optical wavelengths. To develop a multiwavelength oximetry system, a physical
      theory of pulse oximetry must be constructed. In addition, a theory for
      quantitative measurement of optical absorption in an optical scatterer, such as
      in living tissue, remains a difficult theoretical and practical aspect of this
      problem. METHODS: We adopted Schuster's theory of radiation through a foggy
      atmosphere for a basis of theory of pulse oximetry. We considered three factors
      affecting pulse oximetry: the optics, the tissue, and the venous blood. RESULTS:
      We derived a physical theoretical formula of pulse oximetry. The theory was
      confirmed with a full SO2 range experiment. Based on the theory, the three
      wavelength method eliminated the effect of tissue and improved the accuracy of
      Spo2. The five-wavelength method eliminated the effect of venous blood and
      improved motion artifact elimination. CONCLUSIONS: Our theory of multiwavelength
      pulse oximetry can be expected to be useful for solving almost all problems in
      pulse oximetry such as accuracy, motion artifact, low-pulse amplitude, response
      delay, and errors using reflection oximetry which will expand the application of
      pulse oximetry. Our theory is probably a rare case of success in solving the
      difficult problem of quantifying optical density of a substance embedded in an
      optically scattering medium.

PMID- 18048901
TI  - Intrapartum oximetry of the fetus.
AB  - Fetal monitoring during labor aims to identify fetal problems which, if
      uncorrected, may result in morbidity or death. A nonreassuring or abnormal fetal
      heart rate trace by cardiotocography (CTG) does not necessarily equate with fetal
      hypoxia and/or acidosis. However, in the absence of more objective data, the use
      of CTG often results in variable, but inappropriately high, operative delivery
      rates (forceps, vacuum, or cesarean delivery) for nonreassuring fetal status in
      many hospitals. The addition of fetal pulse oximetry (FPO) has the potential to
      improve the assessment of fetal well-being during labor. In this review we
      consider several aspects of FPO. Several factors, such as sensor to skin contact,
      uterine contractions, fetal hair, and caput succedaneum, influence the
      performance and use of FPO. Issues such as clinicians' perspectives of FPO sensor
      placement, maternal perspectives of FPO during labor, and an economic analysis
      have all favored FPO. Several randomized controlled trials (RCTs) of FPO reported
      a reduction in cesarean delivery for nonreassuring fetal status when FPO was
      added to conventional CTG monitoring, with no difference in overall cesarean
      delivery rates. One large RCT reported no difference in mode of birth for any
      indication. Several issues relevant to the future of FPO have been addressed by
      these RCTs, the major issue being that it makes no difference to cesarean rates.
      It may be argued that FPO has a valid clinical use in monitoring the fetus with
      congenital heart block. Additionally, in situations of nonreassuring fetal status
      and dystocia, FPO may provide the necessary reassurance until adequate resources
      for cesarean delivery are available.

PMID- 18048902
TI  - Development of a standardized method for motion testing in pulse oximeters.
AB  - BACKGROUND: Pulse oximeter performance in the presence of motion varies among
      devices and manufacturers because of variations in hardware, software, testing,
      and calibration. Compounding these differences is a lack of uniform
      characterization of motion, and the consequential effects of motion upon the wide
      range of normal and abnormal human physiology. Traditional motion testing
      attempts to standardize motion into a reproducible form by using a mechanical jig
      to produce passive motion of a known amplitude and frequency. This type of motion
      challenge fails to account for the physiologic changes induced by active
      movement. METHODS: We postulate that a more appropriate method for testing the
      performance of pulse oximeters in the presence of motion is to create a feedback
      control loop between the device and the test subject, providing a reproducible,
      actively created, and controlled motion test suitable for standardized testing
      among manufacturers. It is hoped that relying on a signal as seen from the
      oximeter's perspective will enable the creation of a sensitive and reproducible
      test method capable of separating those oximeters that can reject motion artifact
      from those that cannot. RESULTS: Preliminary results have concentrated on
      building the tools and clinical protocols needed to evaluate this method. Some
      basic observations are reported, but insufficient numbers of experienced subjects
      precludes rigorous conclusions. CONCLUSION: We have set the stage for a
      feasibility demonstration using a novel form of testing. With sufficient subjects
      and proper statistical evaluation, a robust test method for assessing the
      performance of pulse oximeters in the presence of motion may be at hand.

PMID- 18048903
TI  - The effect of motion on pulse oximetry and its clinical significance.
AB  - Pulse oximetry is an important diagnostic and patient monitoring tool. However,
      motion can induce considerable error into pulse oximetry accuracy, resulting in
      loss of data, inaccurate readings, and false alarms. We will discuss how motion
      artifact affects pulse oximetry accuracy, the clinical consequences of motion
      artifact, and the methods used by various technologies to minimize the impact of
      the motion noise.

PMID- 18048904
TI  - Maximizing the laboratory setting for testing devices and understanding
      statistical output in pulse oximetry.
AB  - Maximizing the laboratory setting for testing baseline pulse oximetry accuracy in
      an arterial desaturation study requires a study design that considers management
      of several aspects in the physiology of the test subject, special attention to
      the device under test, and great care in the preanalytical (sample handling) and
      analytical (Co-oximeter) phases. Statistics used to describe the resulting SpO2
      performance include Precision (size of the data cloud), Bias (offset of the data
      cloud), and A(rms) (accuracy root mean square), which combines the size and
      offset of the data cloud in one number. The A(rms) is the primary statistic
      required by regulatory organizations to describe general performance over the
      entire saturation range. It does not describe any one point, but is a compilation
      of all points over the range tested. Most pulse oximeters in use today specify an
      A(rms) of 2%. To meet this specification, two-thirds of the readings will be
      within 2% of the Co-oximeter reference; however, some individual readings can be
      as inaccurate as 6% or more. The A(rms) statistic does not have the capacity to
      represent all pulse oximeter behavior. Saturation pop-ups, drop-downs, frozen
      readings, and periods of no reading are not portrayed by the A(rms). The next
      steps in the advancement of regulatory validation testing would be to develop
      standards that include an expanded analysis of pulse oximeter performance by
      assessment of pop-ups, dropouts, frozen readings, and periods of no reading
      through assessment of sensitivity/specificity and possibly a "Performance Index"
      similar to the approach taken by Barker.

PMID- 18048905
TI  - Effective standards and regulatory tools for respiratory gas monitors and pulse
      oximeters: the role of the engineer and clinician.
AB  - Developing safe and effective medical devices involves understanding the
      hazardous situations that can arise in clinical practice and implementing
      appropriate risk control measures. The hazardous situations may have their roots
      in the design or in the use of the device. Risk control measures may be
      engineering or clinically based. A multidisciplinary team of engineers and
      clinicians is needed to fully identify and assess the risks and implement and
      evaluate the effectiveness of the control measures. In this paper, I use three
      issues, calibration/accuracy, response time, and protective measures/alarms, to
      highlight the contributions of these groups. This important information is
      captured in standards and regulatory tools to control risk for respiratory gas
      monitors and pulse oximeters. This paper begins with a discussion of the
      framework of safety, explaining how voluntary standards and regulatory tools
      work. The discussion is followed by an examination of how engineering and
      clinical knowledge are used to support the assurance of safety.

PMID- 18048906
TI  - Mortal and immortal DNA: Craig Venter and Keats's "Lamia".

PMID- 18048907
TI  - Quorum sensing, communication and cross-kingdom signalling in the bacterial
      world.
AB  - Although unicellular, bacteria are highly interactive and employ a range of cell
      to-cell communication or 'quorum sensing (QS)' systems for promoting collective
      behaviour within a population. QS is generally considered to facilitate gene
      expression only when the population has reached a sufficient cell density and
      depends on the synthesis of small molecules that diffuse in and out of bacterial
      cells. As the bacterial population density increases, so does the synthesis of QS
      signal molecules and consequently, their concentration in the external
      environment increases. Once a critical threshold concentration is reached, a
      target sensor kinase or response regulator is activated, so facilitating the
      expression of QS-dependent target genes. Several chemically distinct families of
      QS signal molecules have been described, of which the N-acylhomoserine lactone
      (AHL) family in Gram-negative bacteria have been the most intensively
      investigated. QS contributes to environmental adaptation by facilitating the
      elaboration of virulence determinants in pathogenic species and plant biocontrol
      characteristics in beneficial species as well as directing biofilm formation and
      colony escape. QS also crosses the prokaryotic-eukaryotic boundary in that QS
      signal molecules influence the behaviour of eukaryotic organisms in both the
      plant and mammalian worlds such that QS signal molecules may directly facilitate
      bacterial survival by promoting an advantageous lifestyle within a given
      environmental niche.

PMID- 18048908
TI  - Making sense of quorum sensing in lactobacilli: a special focus on Lactobacillus
      plantarum WCFS1.
AB  - In silico identification criteria were defined to predict if genes encoding
      histidine protein kinases (HPKs) and response regulators (RRs) could be part of
      peptide-based quorum sensing (QS) two-component regulatory systems (QS-TCSs) in
      Firmicutes. These criteria were used to screen HPKs and RRs annotated on the
      completed genome sequences of Lactobacillus species, and several (putative) QS
      TCSs were identified in this way. The five peptide-based QS-TCSs that were
      predicted on the Lactobacillus plantarum WCFS1 genome were further analysed to
      test their (QS) functionality. Four of these systems contained an upstream gene
      encoding a putative autoinducing peptide (AIP), of which two were preceded by a
      double-glycine-type leader peptide. One of these was identical to the plnABCD
      regulatory system of L. plantarum C11 and was shown to regulate plantaricin
      production in L. plantarum WCFS1. The third TCS was designated lamBDCA for
      Lactobacillus agr-like module, where the lamD gene was shown to encode a cyclic
      thiolactone peptide. The fourth TCS was paralogous to the lam system and
      contained a putative AIP-encoding gene but lacked the lamB gene. Finally, a
      genetically separated orphan HPK and RR that showed clear peptide-based QS
      characteristics could form a fifth peptide-based QS-TCS. The predicted presence
      of multiple (peptide-based) QS-TCSs in some lactobacilli and in particular in L.
      plantarum might be a reflection of the ability of these species to persist in a
      diverse range of ecological niches.

PMID- 18048909
TI  - The role of protein secretion systems in the virulence of the intracellular
      pathogen Legionella pneumophila.
AB  - Legionella pneumophila is a Gram-negative facultative intracellular pathogen,
      which multiplies in protozoa in its natural environment and can cause
      Legionnaires' disease in man, following infection of alveolar macrophages. In
      each of the different stages of infection of host cells, virulence proteins need
      to be delivered to their specific place of action and therefore must cross two
      barriers: the inner and the outer membrane. To date, several specialized
      secretion machineries for transport of proteins across the inner and outer
      membrane have been identified in L. pneumophila. Most of these secretion pathways
      have been shown to affect the virulence of this pathogen. An overview will be
      given of all the secretion pathways and the proteins transported by these
      secretion systems identified so far, with special attention paid to those that
      play a role in the pathogenicity of L. pneumophila.

PMID- 18048910
TI  - Cryptococcus neoformans laccase catalyses melanin synthesis from both D- and L
      DOPA.
AB  - The human fungal pathogen Cryptococcus neoformans produces melanin in the
      presence of various substrates, including the L enantiomer of 3,4
      dihydroxyphenylalanine (DOPA). The enzyme laccase catalyses the formation of
      melanin by oxidizing L-DOPA, initiating a series of presumably spontaneous
      reactions that ultimately leads to the polymerization of the pigment in the yeast
      cell wall. There, melanin protects the cell from a multitude of environmental and
      host assaults. Thus, the ability of C. neoformans to produce pigments from a
      variety of available substrates is likely to confer a survival advantage. A
      number of C. neoformans isolates of different serotypes produced pigments from D
      DOPA, the stereoisomer of L-DOPA. Acid-resistant particles were isolated from
      pigmented C. neoformans cells grown in the presence of D-DOPA. Biophysical
      characterization showed the particles had a stably detectable free-radical signal
      by EPR, and negative zeta potential, similar to L-DOPA-derived particles. No
      major differences were found between L- and D-DOPA ghosts in terms of binding to
      anti-melanin antibodies, or in overall architecture when imaged by electron
      microscopy. C. neoformans cells utilized L- and D-DOPA at a similar rate.
      Overall, our results indicate that C. neoformans shows little stereoselectivity
      for utilizing DOPA in melanin synthesis. The ability of C. neoformans to use both
      L and D enantiomers for melanization implies that this organism has access to a
      greater potential pool of substrates for melanin synthesis, and this could
      potentially be exploited in the design of therapeutic inhibitors of laccase.

PMID- 18048911
TI  - Characterization of the ferrioxamine uptake system of Nitrosomonas europaea.
AB  - The chemolithoautotroph Nitrosomonas europaea has two genes predicted to encode
      outer-membrane (OM) ferrioxamine transporters. Expression of the ferrioxamine
      uptake system required induction, as shown by the shorter lag phase in
      ferrioxamine-containing cultures when ferrioxamine-exposed cells were used as an
      inoculum. The two OM ferrioxamine siderophore transporters encoded by foxA(1)
      (NE1097) and foxA(2) (NE1088) were produced only in cells grown in Fe-limited
      ferrioxamine-containing medium. The inactivation of foxA(1), singly or in
      combination with foxA(2), prevented growth in Fe-limited medium containing excess
      desferrioxamine (DFX). The foxA(2)-disrupted single mutant grew poorly in the
      regular Fe-limited (0.2 microM) medium with 10 microM DFX, but grew well when the
      Fe level was raised to 1.0 microM with 10 microM DFX. For efficient acquisition
      of Fe-loaded ferrioxamine, N. europaea needs both ferrioxamine transporters
      FoxA(1) and FoxA(2). FoxA(1) probably regulates its own production, and it
      controls the production of FoxA(2) as well.

PMID- 18048912
TI  - Role of the methylcitrate cycle in propionate metabolism and detoxification in
      Mycobacterium smegmatis.
AB  - Catabolism of odd-chain-length fatty acids yields acetyl-CoA and propionyl-CoA. A
      common pathway of propionyl-CoA metabolism in micro-organisms is the
      methylcitrate cycle, which includes the dedicated enzymes methylcitrate synthase
      (MCS), methylcitrate dehydratase (MCD) and methylisocitrate lyase (MCL). The
      methylcitrate cycle is essential for propionate metabolism in Mycobacterium
      tuberculosis. Unusually, M. tuberculosis lacks an MCL orthologue and this
      activity is provided instead by two isoforms of the glyoxylate cycle enzyme
      isocitrate lyase (ICL1 and ICL2). These bifunctional (ICL/MCL) enzymes are
      jointly required for propionate metabolism and for growth and survival in mice.
      In contrast, the non-pathogenic species Mycobacterium smegmatis encodes a
      canonical MCL enzyme in addition to ICL1 and ICL2. The M. smegmatis gene encoding
      MCL (prpB) is clustered with genes encoding MCS (prpC) and MCD (prpD). Here we
      show that deletion of the M. smegmatis prpDBC locus reduced but did not eliminate
      MCL activity in cell-free extracts. The residual MCL activity was abolished by
      deletion of icl1 and icl2 in the DeltaprpDBC background, suggesting that these
      genes encode bifunctional ICL/MCL enzymes. A DeltaprpB Deltaicl1 Deltaicl2 mutant
      was unable to grow on propionate or mixtures of propionate and glucose. We
      hypothesize that incomplete propionyl-CoA metabolism might cause toxic
      metabolites to accumulate. Consistent with this idea, deletion of prpC and prpD
      in the DeltaprpB Deltaicl1 Deltaicl2 background paradoxically restored growth on
      propionate-containing media. These observations suggest that the marked
      attenuation of ICL1/ICL2-deficient M. tuberculosis in mice could be due to the
      accumulation of toxic propionyl-CoA metabolites, rather than inability to utilize
      fatty acids per se.

PMID- 18048913
TI  - A Mesorhizobium loti mutant with reduced glucan content shows defective invasion
      of its host plant Lotus japonicus.
AB  - Random transposon mutagenesis led to the isolation of a novel Mesorhizobium loti
      mutant that is defective in nitrogen fixation during symbiosis with Lotus
      japonicus. The mutated locus, designated cep, encodes a putative cell-envelope
      protein displaying no significant sequence similarity to proteins with known
      functions. This mutant elicits the formation of nodule-like bumps and root-hair
      curling, but not the elongation of infection threads, on L. japonicus roots. This
      is reminiscent of the phenotypes of rhizobial mutants impaired in cyclic beta
      glucan biosynthesis. The cep mutant exhibits partially reduced content of cell
      associated glucans and intermediate deficiency of motility under hypo-osmotic
      conditions as compared to a glucan-deficient mutant. Second-site pseudorevertants
      of the cep mutant were isolated by selecting for restoration of symbiotic
      nitrogen fixation. A subset of pseudorevertants restored both symbiotic
      capability and glucan content to levels comparable to that of the wild-type.
      These results suggest that the Cep product acts on a successful symbiosis by
      affecting cell-associated glucan content.

PMID- 18048914
TI  - Role of the C-terminal region of dextransucrase from Leuconostoc mesenteroides
      IBT-PQ in cell anchoring.
AB  - dsrP, a gene that encodes a cell-associated dextransucrase produced by
      Leuconostoc mesenteroides IBT-PQ, was isolated, sequenced and expressed in
      Escherichia coli. From sequence analysis, seven repeat units in the N-terminal
      region were found, as well as five cell wall binding repeats in the C-terminal
      region. A model of the C-terminal domain of dextransucrase was built based on the
      solenoid structure of the cell wall binding domain already described in LytA. By
      experiments involving direct interactions of the enzyme with L. mesenteroides
      cells, as well as among the cells and the single C-terminal domain expressed in
      E. coli, evidence was obtained concerning the anchoring function of this region
      in cell-associated dextransucrase, a function which may be independent of its
      capacity to bind dextran.

PMID- 18048915
TI  - Phylogenetic and biochemical characterization of a novel cluster of intracellular
      fungal alpha-amylase enzymes.
AB  - Currently known fungal alpha-amylases are well-characterized extracellular
      enzymes that are classified into glycoside hydrolase subfamily GH13_1. This study
      describes the identification, and phylogenetic and biochemical analysis of novel
      intracellular fungal alpha-amylases. The phylogenetic analysis shows that they
      cluster in the recently identified subfamily GH13_5 and display very low
      similarity to fungal alpha-amylases of family GH13_1. Homologues of these
      intracellular enzymes are present in the genome sequences of all filamentous
      fungi studied, including ascomycetes and basidiomycetes. One of the enzymes
      belonging to this new group, Amy1p from Histoplasma capsulatum, has recently been
      functionally linked to the formation of cell wall alpha-glucan. To study the
      biochemical characteristics of this novel cluster of alpha-amylases, we
      overexpressed and purified a homologue from Aspergillus niger, AmyD, and studied
      its activity product profile with starch and related substrates. AmyD has a
      relatively low hydrolysing activity on starch (2.2 U mg(-1)), producing mainly
      maltotriose. A possible function of these enzymes in relation to cell wall alpha
      glucan synthesis is discussed.

PMID- 18048916
TI  - A novel role for the yeast protein kinase Dbf2p in vacuolar H+-ATPase function
      and sorbic acid stress tolerance.
AB  - In Saccharomyces cerevisiae, the serine-threonine protein kinase activity of
      Dbf2p is required for tolerance to the weak organic acid sorbic acid. Here we
      show that Dbf2p is required for normal phosphorylation of the vacuolar H(+)
      ATPase (V-ATPase) A and B subunits Vma1p and Vma2p. Loss of V-ATPase activity due
      to bafilomycin treatment or deletion of either VMA1 or VMA2 resulted in sorbic
      acid hypersensitivity and impaired vacuolar acidification, phenotypes also
      observed in both a kinase-inactive dbf2 mutant and cells completely lacking DBF2
      (dbf2Delta). Crucially, VMA2 is a multicopy suppressor of both the sorbic acid
      sensitive phenotype and the impaired vacuolar-acidification defect of dbf2Delta
      cells, confirming a functional interaction between Dbf2p and Vma2p. The yeast V
      ATPase is therefore involved in mediating sorbic acid stress tolerance, and we
      have shown a novel and unexpected role for the cell cycle-regulated protein
      kinase Dbf2p in promoting V-ATPase function.

PMID- 18048918
TI  - The group B streptococcal alpha C protein binds alpha1beta1-integrin through a
      novel KTD motif that promotes internalization of GBS within human epithelial
      cells.
AB  - Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis
      and meningitis among neonates and a cause of morbidity among pregnant women and
      immunocompromised adults. GBS epithelial cell invasion is associated with
      expression of alpha C protein (ACP). Loss of ACP expression results in a decrease
      in GBS internalization and translocation across human cervical epithelial cells
      (ME180). Soluble ACP and its 170 amino acid N-terminal region (NtACP), but not
      the repeat protein RR', bind to ME180 cells and reduce internalization of wild
      type GBS to levels obtained with an ACP-deficient isogenic mutant. In the current
      study, ACP colocalized with alpha(1)beta(1)-integrin, resulting in integrin
      clustering as determined by laser scanning confocal microscopy. NtACP contains
      two structural domains, D1 and D2. D1 is structurally similar to fibronectin's
      integrin-binding region (FnIII10). D1's (KT)D146 motif is structurally similar to
      the FnIII10 (RG)D1495 integrin-binding motif, suggesting that ACP binds
      alpha(1)beta(1)-integrin via the D1 domain. The (KT)D146A mutation within soluble
      NtACP reduced its ability to bind alpha(1)beta(1)-integrin and inhibit GBS
      internalization within ME180 cells. Thus ACP binding to human epithelial cell
      integrins appears to contribute to GBS internalization within epithelial cells.

PMID- 18048917
TI  - The voltage-gated Na+ channel NaVBP co-localizes with methyl-accepting chemotaxis
      protein at cell poles of alkaliphilic Bacillus pseudofirmus OF4.
AB  - Na(V)BP, found in alkaliphilic Bacillus pseudofirmus OF4, is a member of the
      bacterial voltage-gated Na(+) channel superfamily. The alkaliphile requires
      Na(V)BP for normal chemotaxis responses and for optimal pH homeostasis during a
      shift to alkaline conditions at suboptimally low Na(+) concentrations. We
      hypothesized that interaction of Na(V)BP with one or more other proteins in vivo,
      specifically methyl-accepting chemotaxis proteins (MCPs), is involved in
      activation of the channel under the pH conditions that exist in the extremophile
      and could underpin its role in chemotaxis; MCPs transduce chemotactic signals and
      generally localize to cell poles of rod-shaped cells. Here, immunofluorescence
      microscopy and fluorescent protein fusion studies showed that an alkaliphile
      protein (designated McpX) that cross-reacts with antibodies raised against
      Bacillus subtilis McpB co-localizes with Na(V)BP at the cell poles of B.
      pseudofirmus OF4. In a mutant in which Na(V)BP-encoding ncbA is deleted, the
      content of McpX was close to the wild-type level but McpX was significantly
      delocalized. A mutant of B. pseudofirmus OF4 was constructed in which cheAW
      expression was disrupted to assess whether this mutation impaired polar
      localization of McpX, as expected from studies in Escherichia coli and
      Salmonella, and, if so, whether Na(V)BP would be similarly affected. Polar
      localization of both McpX and Na(V)BP was decreased in the cheAW mutant. The
      results suggest interactions between McpX and Na(V)BP that affect their co
      localization. The inverse chemotaxis phenotype of ncbA mutants may result in part
      from MCP delocalization.

PMID- 18048919
TI  - Characterization of the mycobacterial chromosome segregation protein ParB and
      identification of its target in Mycobacterium smegmatis.
AB  - Bacterial chromosomes (though not Escherichia coli and some other gamma
      proteobacterial chromosomes) contain parS sequences and parAB genes encoding
      partitioning proteins, i.e. ParA (ATPase) and ParB (DNA-binding proteins) that
      are components of the segregation machinery. Here, mycobacterial parABS elements
      were characterized for the first time. parAB genes are not essential in
      Mycobacterium smegmatis; however, elimination or overexpression of ParB protein
      causes growth inhibition. Deletion of parB also leads to a rather severe
      chromosome segregation defect: up to 10% of the cells were anucleate.
      Mycobacterial ParB protein uses three oriC-proximal parS sequences as targets to
      organize the origin region into a compact nucleoprotein complex. Formation of
      such a complex involves ParB-ParB interactions and is assisted by ParA protein.

PMID- 18048920
TI  - Structure and function of the microbial community in a full-scale enhanced
      biological phosphorus removal plant.
AB  - The structure and function of the microbial community in a full-scale enhanced
      biological phosphorus removal wastewater treatment plant (WWTP; Skagen) were
      investigated using the full-cycle rRNA approach, combined with ecophysiological
      studies. A total of 87 16S rRNA gene sequences were retrieved, and 78 operational
      taxonomic units were identified. Novel oligonucleotide probes were designed, and
      quantitative fluorescence in situ hybridization revealed that six hitherto
      undescribed probe-defined groups within the phylum Bacteroidetes (two groups),
      and classes Betaproteobacteria (two groups) and Gammaproteobacteria (two groups),
      were relatively abundant (>1% of total biovolume) in the Skagen WWTP and 10 other
      full-scale WWTPs with biological P removal. The most abundant was a group of rod
      shaped Bacteroidetes attached to filamentous bacteria, which is distantly related
      to the genus Haliscomenobacter of the family Saprospiraceae, and comprised 9-19%
      of the bacterial biovolume in all the WWTPs investigated. The other five probe
      defined groups were found in all WWTPs, but they were less abundant (1-6%). Two
      groups had a glycogen-accumulating phenotype and one Dechloromonas-related group
      had a polyphosphate-accumulating phenotype, and they were potentially all
      involved in denitrification. In total, about 81% of all bacteria hybridizing with
      the general eubacterial probe were detected in the Skagen WWTP by using clone- or
      group-specific probes, indicating that most members of the microbial community
      had been identified.

PMID- 18048921
TI  - Development of a multilocus sequence typing scheme for intestinal spirochaetes
      within the genus Brachyspira.
AB  - The purpose of this study was to evaluate a multilocus sequence typing (MLST)
      scheme for intestinal spirochaetes of the genus Brachyspira. Eight loci mainly
      coding for enzymes previously used in multilocus enzyme electrophoresis analysis
      of Brachyspira species were examined in 66 Brachyspira field isolates and
      type/reference strains. The isolates and strains were recovered from pigs, birds,
      dogs and a mouse and originated from seven European countries, the USA and
      Canada. Forty-six isolates represented recognized Brachyspira species and 20
      represented provisionally designated species or isolates that have not been
      classified. Only two loci gave PCR products for all 66 strains and isolates, but
      amplicons for seven loci were obtained for 44 of the isolates. Sequences for each
      locus had a DNA allelic variation of 30-47 and an amino acid allelic variation of
      14-47 that gave rise to the same number of sequence and amino acid types (58) for
      the strains and isolates studied. A population snapshot based on sequence and
      amino acid types showed a close phylogenetic relationship amongst the porcine
      isolates from the same geographical regions, and indicated a close evolutionary
      relationship between isolates recovered from pigs and mallards. A general
      concordance was obtained between the MLST groupings and classifications based on
      culture and biochemical tests, 16S rDNA sequence analysis and random amplified
      polymorphic DNA analysis. This is a first step towards establishing an MLST
      system for use in identifying Brachyspira species and determining relationships
      between individual strains and species in the genus.

PMID- 18048922
TI  - Consequences of a sortase A mutation in Streptococcus gordonii.
AB  - Sortase A (SrtA) is required for cell-wall anchoring of LPXTG-containing Gram
      positive surface proteins. It was hypothesized, therefore, that disruption of the
      srtA gene would alter surface anchoring and functions of target LPXTG motif
      bearing SspA and SspB proteins of Streptococcus gordonii. Mutant strains in srtA
      (V288srtA(-), DL1srtA(-)) were constructed in S. gordonii V288 (wtV288) and DL1
      (wtDL1). When compared to wtV288, the V288srtA(-) mutant showed decreased biofilm
      formation on polystyrene, and reduced binding to immobilized purified salivary
      agglutinin (BIAcore analysis). The wtV288 and V288srtA(-) strains were similar in
      ultrastructure, but immunogold-labelled SspA/SspB surface expression was reduced
      on the V288srtA(-) mutant. DL1srtA(-) was also complemented to obtain DL1srtA(+).
      From the wild-type strains (wtV288, wtDL1), srtA(-) mutants (V288srtA(-),
      DL1srtA(-)), and the complemented mutant (DL1srtA(+)), cytoplasmic, cell-wall and
      released extracellular protein fractions were isolated. Each fraction was
      analysed by SDS-PAGE and immunoblotting with anti-P1. Spent medium from srtA(-)
      mutant cells contained over-represented proteins, including SspA/SspB (P1
      antigen). Mutants showed less P1 on the cell surface than wild-types, as
      estimated using whole-cell ELISA, and no P1 appeared in the cytoplasmic
      fractions. Expression of several adhesin genes (sspA/B, cshA/B, fbpA) was
      generally upregulated in the mutants (V288srtA(-), DL1srtA(-)), but restored to
      wild-type levels in DL1srtA(+). These data therefore imply that in addition to
      its role in processing LPXTG-containing adhesins, sortase A has the novel
      function of contributing to transcriptional regulation of adhesin gene
      expression.

PMID- 18048923
TI  - Identification of multiple integration sites for Stx-phage Phi24B in the
      Escherichia coli genome, description of a novel integrase and evidence for a
      functional anti-repressor.
AB  - The key virulence factor in Shiga-toxigenic Escherichia coli is the expression of
      Shiga toxin (Stx), which is conferred by Stx-encoding temperate lambdoid phages
      (Stx-phages). It had been assumed that Stx-phages would behave similarly to
      lambda phage. However, contrary to the lambda superinfection immunity model, it
      has been demonstrated that double lysogens can be produced with the Stx-phage
      Phi24(B). Here, the Phi24(B) integrase gene is identified, and the preferred site
      of integration defined. Although an E. coli int gene was identified close to the
      Phi24(B) integration site, it was shown not to be involved in the phage
      integration event. An additional six potential integration sites were identified
      in the E. coli genome, and three of these were confirmed experimentally. Two of
      the other potential sites lie within genes predicted to be essential to E. coli
      and are therefore unlikely to support phage integration. A Phi24(B) gene,
      possessing similarity to the well-characterized P22 ant gene, was identified. RT
      PCR was used to demonstrate that ant is transcribed in a Phi24(B) E. coli
      lysogen, and expression of an anti-repressor is the likely explanation for the
      absence of immunity to superinfection. Demonstration of the ability of Phi24(B)
      to form multiple lysogens has two potentially serious impacts. First, multiple
      integrated prophages will drive the evolution of bacterial pathogens as novel Stx
      phages emerge following intracellular mutation/recombination events. Second,
      multiple copies of the stx gene may lead to an increase in toxin production and
      consequently increased virulence.

PMID- 18048924
TI  - Organization of the biosynthetic gene cluster for the macrolide antibiotic
      spiramycin in Streptomyces ambofaciens.
AB  - Spiramycin, a 16-membered macrolide antibiotic used in human medicine, is
      produced by Streptomyces ambofaciens; it comprises a polyketide lactone,
      platenolide, to which three deoxyhexose sugars are attached. In order to
      characterize the gene cluster governing the biosynthesis of spiramycin, several
      overlapping cosmids were isolated from an S. ambofaciens gene library, by
      hybridization with various probes (spiramycin resistance or biosynthetic genes,
      tylosin biosynthetic genes), and the sequences of their inserts were determined.
      Sequence analysis showed that the spiramycin biosynthetic gene cluster spanned a
      region of over 85 kb of contiguous DNA. In addition to the five previously
      described genes that encode the type I polyketide synthase involved in
      platenolide biosynthesis, 45 other genes have been identified. It was possible to
      propose a function for most of the inferred proteins in spiramycin biosynthesis,
      in its regulation, in resistance to the produced antibiotic or in the provision
      of extender units for the polyketide synthase. Two of these genes, predicted to
      be involved in deoxysugar biosynthesis, were inactivated by gene replacement, and
      the resulting mutants were unable to produce spiramycin, thus confirming their
      involvement in spiramycin biosynthesis. This work reveals the main features of
      spiramycin biosynthesis and constitutes a first step towards a detailed molecular
      analysis of the production of this medically important antibiotic.

PMID- 18048925
TI  - CsoR regulates the copper efflux operon copZA in Bacillus subtilis.
AB  - The adaptation of Bacillus subtilis to elevated levels of copper ions requires
      the copper-inducible copZA operon encoding a copper chaperone and efflux ATPase.
      Here we identify CsoR (formerly YvgZ) as the copper-sensing repressor that
      regulates the copZA operon. CsoR binds with high affinity to an operator site
      overlapping the copZA promoter and its binding is specifically inhibited by
      copper salts. As previously described, the YhdQ (CueR) protein also binds to the
      copZA regulatory region, but genetic experiments indicate that this protein is
      not responsible for the copper-dependent regulation of this operon.

PMID- 18048926
TI  - VmeAB, an RND-type multidrug efflux transporter in Vibrio parahaemolyticus.
AB  - Genes vmeA and vmeB, encoding a multidrug efflux transporter in the halophilic
      bacterium Vibrio parahaemolyticus, have been cloned using a drug-hypersusceptible
      Escherichia coli strain as the host. Cells of E. coli KAM33 (DeltaacrAB
      DeltaydhE) carrying the vmeAB region from V. parahaemolyticus conferred much
      higher MICs for a variety of antimicrobial agents than did control cells. Cells
      possessing VmeAB under energized conditions maintained very low intracellular
      concentrations of ethidium. This was as expected for an energy-dependent efflux
      system, and supports the notion--based on sequence homology--that VmeAB belongs
      to the resistance nodulation cell division (RND) family of multidrug efflux
      transporters. It is likely that VmeAB forms functional complexes with the outer
      membrane protein TolC in E. coli, because introduction of vmeAB into cells of E.
      coli KAM43, which lacks the tolC gene, failed to elevate the MICs for any of the
      antimicrobial agents tested. Therefore, a V. parahaemolyticus homologue of tolC
      was also cloned, designated vpoC, and was introduced together with vmeAB into
      cells of E. coli KAM43. The MICs of all agents tested were raised and were
      comparable to the values observed in E. coli KAM33 harbouring a plasmid carrying
      vmeAB. Finally, a vmeAB-deficient mutant of V. parahaemolyticus was constructed
      (designated TM3). TM3 showed slightly higher susceptibility than the parental V.
      parahaemolyticus to some antimicrobial agents. Survival rate of the TM3 when
      exposed to deoxycholate decreased compared with that of the parent.

PMID- 18048927
TI  - Comparative analysis of FimB and FimE recombinase activity.
AB  - FimB and FimE are site-specific recombinases, part of the lambda integrase
      family, and invert a 314 bp DNA switch that controls the expression of type 1
      fimbriae in Escherichia coli. FimB and FimE differ in their activity towards the
      fim switch, with FimB catalysing inversion in both directions in comparison to
      the higher-frequency but unidirectional on-to-off recombination catalysed by
      FimE. Previous work has demonstrated that FimB, but not FimE, recombination is
      completely inhibited in vitro and in vivo by a regulator, PapB, expressed from a
      distinct fimbrial locus. The aim of this work was to investigate differences
      between FimB and FimE activity by exploiting the differential inhibition
      demonstrated by PapB. The research focused on genetic changes to the fim switch
      that alter recombinase binding and its structural context. FimB and FimE still
      recombined a switch in which the majority of fimS DNA was replaced with a larger
      region of non-fim DNA. This demonstrated a minimal requirement for FimB and FimE
      recombination of the Fim binding sites and associated inverted repeats. With the
      original leucine-responsive regulatory protein (Lrp) and integration host factor
      (IHF)-dependent structure removed, PapB was now able to inhibit both
      recombinases. The relative affinities of FimB and FimE were determined for the
      four 'half sites'. This analysis, along with the effect of extensive swaps and
      duplications of the half sites on recombination frequency, demonstrated that FimB
      recruitment and therefore subsequent activity was dependent on a single half site
      and its context, whereas FimE recombination was less stringent, being able to
      interact initially with two half sites with equally high affinity. While
      increasing FimB recombination frequencies failed to overcome PapB repression,
      mutations made in recombinase binding sites resulted in inhibition of FimE
      recombination by PapB. Overall, the data support a model in which the
      recombinases differ in loading order and co-operative interactions. PapB exploits
      this difference and FimE becomes susceptible when its normal loading is
      restricted or changed.

PMID- 18048928
TI  - Characterization of a Giardia lamblia WB C6 clone resistant to the isoflavone
      formononetin.
AB  - Giardia lamblia is a common intestinal-dwelling protozoan and causes diarrhoea in
      humans and animals worldwide. For several years, a small number of drugs such as
      the 5-nitroimidazole metronidazole (MET) or the thiazolide nitazoxanide (NTZ)
      have been used for chemotherapy against giardiasis. However, various pre-clinical
      and clinical investigations revealed that antigiardial chemotherapy may be
      complicated by emergence of giardial resistance to these drugs. The present study
      addressed the question if isoflavones with antigiardial activity, such as
      daidzein (DAI) or formononetin (FOR), may serve as alternative compounds for
      treatment of giardiasis. For this purpose, the potential of G. lamblia clone WB
      C6 to form resistance to FOR and related isoflavones was tested in vitro. In the
      line of these experiments, a clone (C3) resistant to isoflavones, but sensitive
      to MET and NTZ, was generated. Affinity chromatography on DAI-agarose using cell
      free extracts of G. lamblia trophozoites resulted in the isolation of a
      polypeptide of approximately 40 kDa, which was identified by mass spectrometry as
      a nucleoside hydrolase (NH) homologue (EAA37551.1). In a nucleoside hydrolase
      assay, recombinant NH hydrolysed all nucleosides with a preference for purine
      nucleosides and was inhibited by isoflavones. Using quantitative RT-PCR, the
      expression of genes that are potentially involved in resistance formation was
      analysed, namely NH and genes encoding variant surface proteins (VSPs, TSA417).
      The transcript level of the potential target NH was found to be significantly
      reduced in C3. Moreover, drastic changes were observed in VSP gene expression.
      This may indicate that resistance formation in Giardia against isoflavones is
      linked to, and possibly mediated by, altered gene expression. Taken together, our
      results suggest FOR or related isoflavones as an alternative antigiardial agent
      to overcome potential problems of resistance to drugs like MET or NTZ. However,
      the capacity of Giardia to develop resistance to isoflavones can potentially
      interfere with this alternative treatment of the disease.

PMID- 18048929
TI  - Analysis of the structure of mycolic acids of Mycobacterium simiae reveals a
      particular composition of alpha-mycolates in strain 'habana' TMC 5135, considered
      as immunogenic in tuberculosis and leprosy.
AB  - Structural analysis of mycolic acids from Mycobacterium simiae (including some
      'habana' strains) was carried out using (1)H-NMR and MS. Results indicated that
      this species presents a general pattern of alpha-, alpha'- and keto-mycolates.
      alpha-Mycolates were composed of a complex mixture of 82 to 89 carbon atoms (C82
      C89), with the predominant molecular species containing two di-substituted
      cyclopropane rings. Among keto-mycolates (C84-C89), those containing one trans di
      substituted cyclopropane ring were the most abundant. The alpha'-mycolates were
      monounsaturated (C64, C66). According to MS and (1)H-NMR data, the strains
      studied differed in fine structural details of alpha-mycolates and keto
      mycolates. Notably, strain 'habana' TMC 5135 (belonging to the 'habana' group,
      and considered as highly immunogenic in tuberculosis and leprosy) presented a
      particular composition of alpha-mycolates, with a major component (C87)
      containing one cis plus one trans di-substituted cyclopropane ring, unlike the
      type strain of M. simiae and other strains of the 'habana' group (IPK-220 and IPK
      337R), in which the major component (C84) contained two cis di-substituted
      cyclopropane rings. In spite of this finding, the 'habana' strains were closely
      related to each other and mainly differed from the type strain of M. simiae in
      some details of the fine structure of keto-mycolates. The present work indicated
      that within an identical general pattern of mycolic acids, there is a complex
      composition in M. simiae and structural variation among different strains, as
      reported for pathogenic species of the genus. Noteworthy was the particular
      composition of alpha-mycolates in strain 'habana' TMC 5135.

PMID- 18048930
TI  - Identification of the dehydratase component of the mycobacterial mycolic acid
      synthesizing fatty acid synthase-II complex.
AB  - Mycolic acids are vital components of the Mycobacterium tuberculosis cell wall
      and are essential for survival. While most components of the fatty acid synthase
      II (FAS-II) enzymic machinery that synthesizes these long chain alpha-alkyl, beta
      hydroxy fatty acids have been identified, the gene encoding the beta-hydroxyacyl
      acyl carrier protein (ACP) dehydratase activity has remained elusive. Recent
      bioinformatics-based studies and drug inhibition experiments have identified the
      M. tuberculosis gene Rv0636 as a promising candidate for this role. Using a
      recently described, specialized transduction-based genetic tool we now
      demonstrate that MSMEG1341, the Mycobacterium smegmatis homologue of Rv0636, is
      an essential gene; null mutants of the gene could only be generated in a
      merodiploid strain which contained a second integrated acetamide-inducible copy
      of MSMEG1341. Growth of the conditional mutant in the absence of acetamide
      resulted in loss of mycolic acid biosynthesis and eventually loss of viability
      due to cell lysis. Null MSMEG1341 mutants could also be generated in a M.
      smegmatis strain containing an integrated copy of Rv0636, indicating that Rv0636
      was the functional counterpart of MSMEG1341 in M. tuberculosis. Our results
      demonstrate that MSMEG1341 is an essential gene involved in mycolic acid
      biosynthesis and encodes the FAS-II beta-hydroxyacyl-ACP dehydratase.

PMID- 18048931
TI  - Cloning, characterization and expression of a gene encoding dihydroxyacetone
      synthase in Mycobacterium sp. strain JC1 DSM 3803.
AB  - Dihydroxyacetone synthase (DHAS) is a key enzyme involved in the assimilation of
      methanol in Mycobacterium sp. strain JC1 DSM 3803. The structural gene encoding
      DHAS in Mycobacterium sp. strain JC1 was cloned using random-primed probes
      synthesized after PCR with synthetic primers based on the amino acid sequences
      conserved in two yeast DHASs and several transketolases. The cloned gene, dasS,
      had an ORF of 2193 nt, encoding a protein with a calculated molecular mass of
      78,197 Da. The deduced amino acid sequence of dasS contained an internal sequence
      of Mycobacterium sp. strain JC1 DHAS and exhibited 29.2 and 27.3 % identity with
      those of Candida boidinii and Hansenula polymorpha enzymes, respectively.
      Escherichia coli transformed with the cloned gene produced a novel protein with a
      molecular mass of approximately 78 kDa, which cross-reacted with anti-DHAS
      antiserum and exhibited DHAS activity. Primer-extension analysis revealed that
      the transcriptional start site of the gene was the nucleotide A located 31 bp
      upstream from the dasS start codon. RT-PCR showed that dasS was transcribed as a
      monocistronic message. Northern hybridization and beta-galactosidase assay with
      the putative promoter region of dasS revealed that the gene was transcribed only
      in cells growing on methanol. The expression of dasS in Mycobacterium sp. strain
      JC1 was free from catabolite repression.

PMID- 18048932
TI  - Protein expression diversity amongst serovars of Salmonella enterica.
AB  - Salmonella enterica is one of the most extensively studied bacterial species in
      terms of physiology, genetics, cell culture and development. As a very diverse
      group, the serovars of S. enterica display a spectrum of host specificities
      ranging from a broad host range to strictly host-adapted variants. This study
      utilized a classic proteomic approach combining 2D gel electrophoresis and mass
      spectrometry for the comparative analysis of the proteomes of serovars
      Typhimurium, Enteritidis, Choleraesuis, Pullorum and Dublin. The comparative
      analysis revealed species-specific protein factors with no significant change in
      expression amongst all isolates, as well as proteins with fluctuating expression
      levels between serovars and strains. Examples include an isoform of SodA specific
      for serovar Typhimurium, the third isoform of the lysine arginine ornithine (LAO)
      binding amino acid transporter specific for serovar Pullorum, and the enzyme GabD
      found to be unique to serovar Choleraesuis. Overall the study demonstrated the
      importance of using multiple isolates when characterizing the expression patterns
      of bacteria in order to account for the intrinsic diversity of a bacterial
      population and revealed several factors with potential roles in host adaptation
      and pathogenicity of the serovars of S. enterica.

PMID- 18048933
TI  - Transcriptome profiling of Paracoccidioides brasiliensis yeast-phase cells
      recovered from infected mice brings new insights into fungal response upon host
      interaction.
AB  - Paracoccidioides brasiliensis is a fungal human pathogen with a wide distribution
      in Latin America. It causes paracoccidioidomycosis, the most widespread systemic
      mycosis in Latin America. Although gene expression in P. brasiliensis had been
      studied, little is known about the genome sequences expressed by this species
      during the infection process. To better understand the infection process, 4934
      expressed sequence tags (ESTs) derived from a non-normalized cDNA library from P.
      brasiliensis (isolate Pb01) yeast-phase cells recovered from the livers of
      infected mice were annotated and clustered to a UniGene (clusters containing
      sequences that represent a unique gene) set with 1602 members. A large-scale
      comparative analysis was performed between the UniGene sequences of P.
      brasiliensis yeast-phase cells recovered from infected mice and a database
      constructed with sequences of the yeast-phase and mycelium transcriptome (isolate
      Pb01) (https://dna.biomol.unb.br/Pb/), as well as with all public ESTs available
      at GenBank, including sequences of the P. brasiliensis yeast-phase transcriptome
      (isolate Pb18) (http://www.ncbi.nlm.nih.gov/). The focus was on the overexpressed
      and novel genes. From the total, 3184 ESTs (64.53%) were also present in the
      previously described transcriptome of yeast-form and mycelium cells obtained from
      in vitro cultures (https://dna.biomol.unb.br/Pb/) and of those, 1172 ESTs (23.75%
      of the described sequences) represented transcripts overexpressed during the
      infection process. Comparative analysis identified 1750 ESTs (35.47% of the
      total), comprising 649 UniGene sequences representing novel transcripts of P.
      brasiliensis, not previously described for this isolate or for other isolates in
      public databases. KEGG pathway mapping showed that the novel and overexpressed
      transcripts represented standard metabolic pathways, including glycolysis, amino
      acid biosynthesis, lipid and sterol metabolism. The unique and divergent
      representation of transcripts in the cDNA library of yeast cells recovered from
      infected mice suggests differential gene expression in response to the host
      milieu.

PMID- 18048934
TI  - SufA--a novel subtilisin-like serine proteinase of Finegoldia magna.
AB  - Finegoldia magna is an anaerobic Gram-positive bacterium and commensal, which is
      also associated with clinically important conditions such as skin and soft tissue
      infections. This study describes a novel subtilisin-like extracellular serine
      proteinase of F. magna, denoted SufA (subtilase of Finegoldia magna), which is
      believed to be the first subtilase described among Gram-positive anaerobic cocci.
      SufA is associated with the bacterial cell surface, but is also released in
      substantial amounts during bacterial growth. Papain was used to release SufA from
      the surface of F. magna and the enzyme was purified by ion-exchange
      chromatography and gel filtration. A protein band on SDS-PAGE corresponding to
      the dominating proteolytic activity on gelatin zymography was analysed by MS/MS.
      Based on the peptide sequences obtained, the sufA gene was sequenced. The gene
      comprises 3466 bp corresponding to a preprotein of 127 kDa. Like other members of
      the subtilase family, SufA contains the catalytic triad of aspartic acid,
      histidine and serine with surrounding conserved residues. A SufA homologue was
      identified in 33 of 34 investigated isolates of F. magna, as revealed by PCR and
      immunoprinting. The enzyme forms dimers, which are more proteolytically active
      than the monomeric protein. SufA was found to efficiently cleave and inactivate
      the antibacterial peptide LL-37 and the CXC chemokine MIG/CXCL9, indicating that
      the enzyme promotes F. magna survival and colonization.

PMID- 18048936
TI  - The stringent response of Bacillus anthracis contributes to sporulation but not
      to virulence.
AB  - The Gram-positive, spore-forming pathogen Bacillus anthracis is the aetiological
      agent of anthrax. Its main virulence factors are two toxins and an anti
      phagocytic capsule. When B. anthracis is grown in laboratory culture, the highest
      expression of the anthrax toxin genes occurs during entry into stationary phase,
      suggesting that nutrient limitation is an environmental cue which induces toxin
      production. A common bacterial response to starvation is the so-called stringent
      response, in which the hyperphosphorylated guanosine nucleotide (p)ppGpp is the
      effector molecule. In Escherichia coli, Bacillus subtilis and other bacteria,
      accumulation of this molecule leads to down-regulation of stable RNA synthesis
      and upregulation of the expression of genes involved in survival under nutrient
      poor conditions. This study focuses on the stringent response of B. anthracis. We
      show that in B. anthracis the relA gene is responsible for the synthesis of
      (p)ppGpp and the stringent down-regulation of stable RNA synthesis upon
      starvation for the essential amino acids isoleucine, leucine and valine. The
      deletion of relA did not affect the expression of the virulence gene pagA or
      virulence in a mouse model of infection. In contrast, spore counts upon growth
      and sporulation in a defined medium were approximately 10,000-fold lower for the
      relA deletion mutant than for the parental strain. The contribution of the
      stringent response to efficient sporulation of B. anthracis is notable, as this
      suggests that the stringent response may contribute to the persistence of B.
      anthracis in the natural environment.

PMID- 18048935
TI  - Regulation of the Pseudomonas aeruginosa toxA, regA and ptxR genes by the iron
      starvation sigma factor PvdS under reduced levels of oxygen.
AB  - The level of environmental oxygen (EO) within various Pseudomonas aeruginosa
      infection sites is low (microaerobic), and this can affect the production of
      different virulence factors. Expression of the toxA gene, encoding exotoxin A
      (ETA), is regulated by regA, ptxR and pvdS. Moreover, the iron-starvation sigma
      factor PvdS directs the transcription of pyoverdine siderophore genes (e.g.
      pvdD). DNA-protein binding analysis using recombinant PvdS showed that the PvdS
      RNA polymerase holoenzyme complex specifically bound the toxA, regA and ptxR
      promoter regions. All three promoters contain a PvdS-binding site, the iron
      starvation box. To determine the relationship between these different genes and
      PvdS, we conducted a comparative analysis of toxA, regA, ptxR and pvdD
      transcription throughout the growth cycle of wild-type P. aeruginosa and its pvdS
      mutant in iron-deficient medium under aerobic-shaking (A-sh) and microaerobic
      static (M-st) conditions. Under both EO conditions, optimal toxA, regA and pvdD
      expression and pyoverdine production required PvdS, while ptxR expression was
      moderately dependent on PvdS only under A-sh conditions. Expression of regA, pvdD
      and pyoverdine production in wild-type P. aeruginosa was significantly lower
      under M-st in comparison with A-sh conditions, while the opposite was observed
      for toxA and ptxR. Although low, the level of toxA expression and ETA production
      in the pvdS mutant were higher under M-st than under A-sh conditions.
      Transcription of pvdS and PvdS expression were also reduced by low EO. We propose
      that the regulation of toxA expression under aerobic conditions primarily
      involves PvdS, while an additional EO-responsive regulator(s) besides PvdS is
      required under low EO levels. Thus, PvdS may control the transcription of the
      ptxR, regA and toxA genes, and respond to EO by acting at different levels of the
      toxA regulatory cascade.

PMID- 18048937
TI  - Invasion of HeLa cells by group B streptococcus requires the phosphoinositide-3
      kinase signalling pathway and modulates phosphorylation of host-cell Akt and
      glycogen synthase kinase-3.
AB  - The group B streptococcus (GBS) is an opportunistic bacterial pathogen with the
      ability to cause invasive disease. While the ability of GBS to invade a number of
      host-cell types has been clearly demonstrated, the invasion process is not well
      understood at the molecular level. What has been well established is that
      modulation of host-cell actin microfilaments is essential for GBS invasion to
      occur. Phosphoinositide-3 kinase (PI3K) is a key regulator of the cytoskeleton in
      eukaryotic cells. Our goal in this investigation was to explore the role of the
      PI3K/Akt signalling pathway in epithelial cell invasion by GBS. The epithelial
      cell invasion process was mimicked using the HeLa 229 cell-culture model.
      Treating HeLa cells with chemical inhibitors of PI3K, Akt or Ras prior to
      bacterial infection inhibited GBS invasion but not attachment; treatment with 30
      microM LY294002 (PI3K inhibitor) reduced GBS invasion by 75%, 20 microM L-6
      hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (ICIO) (Akt
      inhibitor) reduced GBS invasion by 50%, and 10 microM manumycin A (Ras inhibitor)
      inhibited GBS invasion by 90%. Genetic inactivation of the p85alpha or p110alpha
      PI3K subunits in HeLa cells also reduced GBS invasion by 55 and 30%,
      respectively. Western blot analysis revealed that phosphorylation of host-cell
      Akt and glycogen synthase kinase-3 (GSK-3) occurs in response to GBS infection,
      and that this is mediated upstream by PI3K. Infection of HeLa cells with GBS
      triggers pro-survival signalling and protects the HeLa cells from camptothecin
      induced caspase-3 cleavage. The results from this investigation show that GBS
      both requires and activates the PI3K/Akt host-cell signalling pathway during
      invasion of epithelial cells.

PMID- 18048938
TI  - Characterization of the NAD-glycohydrolase in streptococcal strains.
AB  - The NADase (Nga) of group A streptococci (GAS) has been implicated in the
      pathogenesis of diseases such as streptococcal toxic shock-like syndrome (STSS)
      and necrotizing fasciitis. In this study we found that the proportion of NADase
      positive strains among clinical isolates in Japan has increased over time. The
      GAS strains studied could be divided into three groups: strains lacking NADase
      activity, strains with low NADase activity, and strains with high NADase
      activity. The older strains, isolated before 1989, belonged to the 'no activity'
      group. Analysis using GST-Nga recombinants revealed that nga alleles of
      representative older strains encode inactive Nga. Mutational analysis of the GST
      Nga recombinants suggested that residue 330 could be associated with reduced
      activity, based upon deduced amino acid sequences. We also investigated NADase
      activity of streptococcal strains other than GAS. All group G streptococcal
      isolates from STSS patients possessed nga genes encoding active enzymes.

PMID- 18048939
TI  - Osmotic adaptation of the halophilic fungus Hortaea werneckii: role of osmolytes
      and melanization.
AB  - This study was intended to determine the osmoadaptation strategy of Hortaea
      werneckii, an extremely salt-tolerant melanized ascomycetous fungus that can grow
      at 0-5.1 M NaCl. It has been shown previously that glycerol is the major
      compatible solute in actively growing H. werneckii. This study showed that the
      exponentially growing cells also contained erythritol, arabitol and mannitol at
      optimal growth salinities, but only glycerol and erythritol at maximal
      salinities. The latter two were both demonstrated to be major compatible solutes
      in H. werneckii, as their decrease correlated with the severity of hypoosmotic
      shock. Besides higher amounts of erythritol and lower amounts of glycerol,
      stationary-phase cells also contained mycosporine-glutaminol-glucoside, which
      might act as a complementary compatible solute. H. werneckii is constitutively
      melanized under various salinity conditions. Ultrastructural study showed
      localization of melanin in the outer parts of the cell wall as a distinct layer
      at optimal salinity (0.86 M NaCl), whereas cell-wall melanization diminished at
      higher salinities. The role of melanized cell wall in the effective retention of
      glycerol is already known, and was also demonstrated in H. werneckii by lower
      retention of glycerol in cells with blocked melanization compared to melanized
      cells. However, these non-melanized cells compensated for the lower amounts of
      glycerol with higher amounts of erythritol and arabitol. We hypothesize that H.
      werneckii melanization is effective in reducing the permeability of its cell wall
      to its major compatible solute glycerol, which might be one of the features that
      helps it tolerate a wider range of salt concentrations than most organisms.

PMID- 18048940
TI  - Molecular characterization of the copper transport system in Staphylococcus
      aureus.
AB  - The Staphylococcus aureus copA gene codes for a putative copper-translocating P
      type ATPase and the downstream copZ gene codes for a copper chaperone. Genome
      database analyses demonstrate that these copper transport genes are highly
      conserved in S. aureus. The expression of copA and copZ was inducible by copper
      and to some extent by ferric and lead ions. A mutant strain containing a
      partially deleted copA gene was more sensitive than the parent strain to copper,
      ferric and lead ions. The copper-sensitive phenotype was due to the accumulation
      of intracellular copper and thus the copA product is involved in the export of
      copper ions. The metal-sensitive phenotype of the mutant was complemented in
      trans by a 2.7 kbp DNA containing copA. We have cloned and overexpressed the
      metal-binding domains of CopA and CopZ and have shown by site-directed
      mutagenesis that the cysteine residues in the CXXC metal-binding motif in CopA
      are involved in copper binding and thus play an important role in copper
      transport in S. aureus.

PMID- 18048942
TI  - Effects of vibration exercise on muscle performance and mobility in an older
      population.
AB  - This study was designed to investigate the effects of vibration on muscle
      performance and mobility in a healthy, untrained, older population. Forty-three
      participants (23 men, 20 women, 66-85 y old) performed tests of sit-to-stand
      (STS), 5- and 10-m fast walk, timed up-and-go test, stair mobility, and strength.
      Participants were randomly assigned to a vibration group, an exercise
      withoutvibration group, or a control group. Training consisted of 3 sessions/wk
      for 2 mo. After training, the vibration and exercise groups showed improved STS
      (12.4%, 10.2%), 5-m fast walk (3.0%, 3.7%), and knee-extension strength (8.1%,
      7.2%) compared with the control (p < 0.05). Even though vibration training
      improved lower limb strength, it did not appear to have a facilitatory effect on
      functional-performance tasks compared with the exercise-without-vibration group.
      Comparable mobility and performance changes between the experimental groups
      suggest that improvements are linked with greater knee-extension strength and
      largely attributed to the unloaded squats performed by both exercise groups.

PMID- 18048941
TI  - The role of glucose kinase in carbohydrate utilization and extracellular
      polysaccharide production in Xanthomonas campestris pathovar campestris.
AB  - The genome of the Xanthomonas campestris pathovar campestris (Xcc) strain 8004
      encodes three uncharacterized proteins, XC1166, XC1223 and XC1976, annotated as
      glucose kinase (Glk) by bioinformatic studies. Here we have investigated the
      biochemical characteristics and physiological roles of these proteins with
      particular reference to the synthesis of extracellular polysaccharide (EPS).
      XC1166, XC1223 and XC1976 were overexpressed as fusion proteins with a His(6)
      affinity tag and purified by nickel affinity chromatography. The standard Glk
      activity assay revealed that all three proteins possessed apparent Glk activity,
      with XC1976-His(6) being the most active; the specific activity values were
      1.16x10(6) U mg(-1) for XC1166-His(6), 4.36x10(7) U mg(-1) for XC1223-His(6) and
      2.63x10(8) U mg(-1) for XC1976-His(6). TLC analysis showed, however, that only
      XC1976-His(6) could phosphorylate glucose. Insertional mutants of XC1166, XC1223
      and XC1976 were generated using the suicide plasmid pK18mob. Although mutant
      strains with insertions in XC1166 or XC1223 had Glk activity similar to that of
      the wild-type strain, the XC1976 mutant had only about 6% of the wild-type
      activity. Mutation in XC1976 had complex effects on EPS production. In media
      containing arabinose, glucose, galactose, sucrose or maltose, the XC1976 mutant
      produced about 40-75% of the wild-type level of EPS, whereas in medium containing
      fructose, the mutant showed a 30% increase in EPS production compared to the wild
      type strain. The XC1976 mutant also showed attenuated virulence on the host plant
      Chinese radish (Raphanus sativus). The results indicate that XC1976 has the most
      significant role for the parameters tested.

PMID- 18048943
TI  - Dimensions of subjective well-being and effects of physical activity in Chinese
      older adults.
AB  - Subjective well-being (SWB) and its relationship with physical activity have not
      been systematically investigated in older Chinese people. This study explored
      these issues using qualitative interviews with a purposive sample of 23 community
      dwelling Chinese older adults (age 55-78 y, 12 women); 16 were physically active
      and 7 physically inactive. Using cross-case analyses, 7 dimensions of SWB
      emerged: physical, psychological, developmental, material, spiritual,
      sociopolitical, and social. Although elements of SWB may be shared across
      cultures, specific distinctions were identified. Active respondents reported the
      unique contributions of physical activity to the physical, psychological,
      developmental, and social elements of SWB. The findings suggest that physical
      activity could enhance the quality of life in Chinese older adults.

PMID- 18048944
TI  - Development and evaluation of the physical activity questionnaire for elderly
      Japanese: the Nakanojo study.
AB  - The Physical Activity Questionnaire for Elderly Japanese (PAQ-EJ) is a self
      administered physical activity questionnaire for elderly Japanese; the authors
      report here on its repeatability and direct and indirect validity. Reliability
      was assessed by repeat administration after 1 month. Direct validation was based
      on accelerometer data collected every 4 s for 1 month in 147 individuals age 65
      85 years. Indirect validation against a 10-item Barthel index (activities of
      daily living [ADL]) was completed in 3,084 individuals age 65-99 years. The test
      retest coefficient was high (r = .64-.71). Total and subtotal scores for lower
      (transportation, housework, and labor) and higher intensity activities
      (exercise/sports) were significantly correlated with step counts and durations of
      physical activity <3 and >or=3 METs (r = .41, .28, .53), respectively.
      Controlling for age and ADL, scores for transportation, exercise/sports, and
      labor were greater in men, but women performed more housework. Sex- and ADL- or
      age-adjusted PAQ-EJ scores were significantly lower in older and dependent
      people. PAQ-EJ repeatability and validity seem comparable to those of instruments
      used in Western epidemiological studies.

PMID- 18048945
TI  - Operationalizing environmental indicators for physical activity in older adults.
AB  - This qualitative study describes environmental supports and barriers to physical
      activity in an older adult sample drawn from low- and high-walkable
      neighborhoods. Thirty-seven individuals age 55 and over were recruited and
      answered open-ended survey questions, with a subsample invited back to partake in
      a semistructured interview. Content analysis identified categories and themes
      linking perceptions of neighborhood-environment characteristics to activity.
      Emerging categories and themes did not differ across neighborhood walkability, so
      results are presented for both groups combined. Infrastructure was the most
      common category identified to encourage activity, specifically, well-maintained
      sidewalks, bike paths or lanes, and traffic control. Other categories of land
      use, landscape, and aesthetics were reported. Poorly maintained or missing
      sidewalks, crosswalks, bike paths or lanes, and traffic safety were categories
      that discouraged activity. In conclusion, the information obtained is helpful in
      solidifying which environmental characteristics are important to measure as they
      relate to activity behavior in an older adult population.

PMID- 18048946
TI  - Environmental changes to increase physical activity: perceptions of older urban
      ethnic-minority women.
AB  - Despite the numerous benefits of physical activity, older adults continue to be
      more sedentary than their younger counterparts, and sedentary behavior is more
      prevalent among older racial and ethnic minorities than among Whites. This study
      used the nominal group technique (NGT) to examine participants' perceptions of
      what neighborhood environmental changes would encourage greater physical activity
      for older African American and Hispanic women. Participants age 50-75 years were
      recruited from 2 urban community health clinics. Nine NGT sessions (45
      participants) were conducted. The women were asked what changes in their
      neighborhood environment would encourage them to become more physically active.
      Responses to the research question were tabulated, and qualitative analysis was
      used to identify themes and categories. Major categories were physical
      environment changes, safety, and activities/social support. Although the physical
      environment received the greatest number of points, concerns for personal safety
      cut across categories. Participants indicated the need for more facilities in
      which to be active.

PMID- 18048947
TI  - The reliability and validity of the physical activity survey in long-term care.
AB  - The purpose of this study was to develop and test a measure of physical activity
      for residents in long-term-care facilities, the Physical Activity Survey in Long
      Term Care (PAS-LTC). Sixty-six activities are included in the PAS-LTC: routine
      physical activity, personal-care activities, structured exercise, recreational
      activities, caretaking activities, and repetitive activities. The study included
      13 residents in a long-term-care facility, most of whom were women (62%), with an
      average age of 84 years (+/- 6.0) and an average Mini Mental State Examination
      score of 6 (+/- 6.9). There was evidence of interrater reliability of the PAS-LTC
      with intraclass correlations of .83-.94. There was some evidence of validity of
      the measure with statistically significant correlations between PAS-LTC recorded
      during the evening and night shifts and the number of counts of activity per the
      ActiGraph (r = .60 and r = .57, respectively, p < .05) and the calories estimated
      (r = .58 and r = .60, respectively, p < .05). The PAS-LTC completed during the
      day shift and total activity based on the PAS-LTC showed nonsignificant
      correlations of .40 or greater with the ActiGraph activity counts and calories.

PMID- 18048948
TI  - Assessment of impairments that limit exercise and use of impairment information
      to generate an exercise.
AB  - Prescribing the correct exercise program is a challenge for older adults with
      multiple physiological impairments. The authors evaluated an assessment
      instrument that incorporates results of multiple categories of impairment,
      including strength, balance, gait, vision, and cognitive function. The physical
      therapist made judgments on the relative impact of 9 different impairments on
      specific exercises and on the total impact of all impairments on particular
      exercises. In a cohort age 75-85 y, functional limitations, impaired balance,
      pain, and low physical endurance were estimated to have the largest impact on the
      ability to carry out exercise activities, primarily walking, stair climbing,
      balance exercises, and stationary bicycling. The assessments revealed that the
      ability to exercise was related to objective measures of function, indicating
      that the therapist incorporated such objective measures into the impairment
      impact rating. The impairment-impact assessment facilitates creating
      individualized exercise prescriptions for individuals with impairments.

PMID- 18048949
TI  - Statins: a new insight into their mechanisms of action and consequent pleiotropic
      effects.
AB  - In the recent years, 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase
      inhibitors have emerged as the most important class of lipid-lowering agents.
      Through inhibition of HMG-CoA reductase, they restrict the rate-limiting step of
      cholesterol synthesis resulting in up-regulation of low density lipoproteins
      (LDL) receptors on the cell membrane and reduction of atherogenic LDL
      consequences. The wide spectrum of non-lipid-mediated pleiotropic effects of
      statins includes: improvement of endothelial dysfunction, increased nitric oxide
      bioavailability, antioxidant effects, anti-inflammatory and immunomodulatory
      properties, stabilization of atherosclerotic plaques and inhibition of cardiac
      hypertrophy. Several clinical trials have demonstrated and confirmed these
      beneficial effects of statins in cardiovascular disorders, in primary and
      secondary prevention settings. Recent studies have reported that the
      physiological background of the widespread therapeutic efficacy of HMG
      CoAreductase inhibitors involved various mechanisms, partially associated with
      statin impact on posttranslational modifications (e.g. prenylation process). In
      this review, we have focused on some of them, especially including the statin
      impact on the endothelial dysfunction and inflammation, peroxisome poliferator
      activated receptor (PPAR), beta-adrenergic signaling, renin-angiotensin system
      and their possible mutual mechanistic linkage.

PMID- 18048950
TI  - Growth hormone therapy in children and adults.
AB  - Growth hormone (GH) is a polypeptide hormone, secreted by somatotropic cells of
      the anterior part of the hypophysis. Its application in therapy, first limited to
      GH deficient children, has now been widened to various other clinical conditions,
      not necessarily related to short stature. Clinical trials conducted in recent
      years have proved the safety of its administration in both children and adults.
      The efficacy of this form of therapy varies, according to different authors, from
      enthusiastic data to very critical opinions. For many pediatric diseases, such as
      GH deficiency or Turner syndrome, GH is regarded by many experts, despite the
      high costs of the therapy, as the first-line treatment. Mounting evidence
      suggests that GH is safe and effective also in children with chronic renal
      failure and cystic fibrosis. Recently, it has also been administered to adults
      with GH deficiency and short bowel syndrome. The aim of this paper is to
      summarize the current data on GH administration in modern pharmacotherapy. In
      this paper we have included the results of the recently published studies and
      discussed not commonly known indications for GH therapy, as well as its
      experimental administration in both children and adults.

PMID- 18048951
TI  - Modulatory role of 5-HT1B receptors in the discriminative signal of amphetamine
      in the conditioned taste aversion paradigm.
AB  - Drugs of abuse, such as amphetamine (AMPH), share the ability to activate the
      mesolimbic dopamine (DA) system. The behavioral effects of AMPH are largely
      mediated by increased DA neurotransmission in the nucleus accumbens. However,
      there is evidence that serotonin (5-hydroxytryptamine - 5-HT) systems may
      regulate forebrain DA function. We examined the role of 5-HT1B receptors on the
      discriminative stimulus properties of AMPH using conditioned taste aversion (CTA)
      as the drug discrimination procedure. Male Wistar rats were deprived of water and
      trained in the CTA procedure. They received the administration of AMPH (1.0
      mg/kg) before a 10 min period of access to saccharin solution and followed by an
      injection of LiCl; on alternate days, rats received saline before and after the
      access to saccharin solution. In generalization and combination tests, the
      training dose of AMPH was substituted by 5-HT1B receptor ligands RU24969 (5-HT1B
      agonist: 0.1, 0.3 and 1.0 mg/kg), CP94253 (5-HT1B agonist: 1.0, 3.0 and 5.6
      mg/kg) and GR127935 (5-HT1B antagonist: 0.3, 1.0 and 3.0 mg/kg) or a combination
      of RU24969 (0.1, 0.3 and 1.0 mg/kg), CP94253 (1.0, 3.0 and 5.6 mg/kg) or GR127935
      (0.3, 1.0 and 3.0 mg/kg) with AMPH (0.3 mg/kg) or GR127935 (0.3, 1.0 and 3.0
      mg/kg) and CP94253 (5.6 mg/kg) with AMPH (0.3 mg/kg). The results showed that 5
      HT1B agonists RU24969 and CP94253 produced partial generalization of 48% and 60%,
      respectively, and the 5-HT1B antagonist GR127935 neither substituted for AMPH nor
      affected the discriminative cue of AMPH; however, when RU24969 or CP94253 were
      administrated in combination with AMPH, they increased the discriminative cue of
      AMPH. This effect was reversed by the administration of 5-HT1B antagonist
      GR127935. These data suggest that 5-HT1B receptors play a modulatory role in the
      discriminative cue of AMPH.

PMID- 18048952
TI  - Chronic imipramine treatment reduces inhibitory properties of group II mGlu
      receptors without affecting their density or affinity.
AB  - An increasing body of evidence indicates an important role of the glutamatergic
      system in the pathophysiology of depression. Not only ionotropic but also
      metabotropic glutamate receptors (mGlu receptors) have been suggested to be
      involved in the mechanism of action of antidepressant drugs. Moreover, several
      mGlu receptor ligands possess a great antidepressant potential. Group II mGlu
      receptor antagonists have been shown to induce antidepressant-like effects in
      rodents. An influence of chronic antidepressant treatment on group II mGlu
      receptors has also been suggested. In our studies, we examined an influence of
      repeated (21-day) imipramine treatment on the density of group II mGlu receptors
      and affinity of mGlu2 and mGlu3 receptor radioligand [3H]-LY341495 for group II
      mGlu receptors in the rat brain hippocampus and frontal cortex. Moreover, we
      analyzed an influence of chronic imipramine administration on the ability of
      group II mGlu receptor agonist, 2R,4R-APDC, to inhibit forskolin-stimulated cAMP
      accumulation in the rat brain cortical slices. We found that inhibitory
      properties of group II mGlu receptors were diminished after chronic, but not
      acute imipramine administration. However, no changes in the density or affinity
      of the mGlu2 and mGlu3 receptor ligand for group II mGlu receptors were observed.

PMID- 18048953
TI  - Effects of some new antiepileptic drugs and progabide on glucocorticoid receptor
      mediated gene transcription in LMCAT cells.
AB  - Antiepileptic drugs affect endocrine and immune system activity, however, it is
      not clear whether these effects are indirect, via interference with
      neurotransmitters, membrane receptors and ion channels or maybe independent of
      neuronal mechanisms. In order to shed more light on this problem, in the present
      study, we evaluated effects of some new-generation antiepileptic drugs and
      progabide as a GABA-mimetic on the corticosterone-induced chloramphenicol
      acetyltransferase (CAT) activity in mouse fibroblast cells stably transfected
      with mouse mammary tumor virus (MMTV)-CAT plasmid. Treatment of cells with
      felbamate for five days inhibited in a concentration-dependent manner (3-100
      microM) the corticosterone-induced reporter gene transcription. Progabide and
      loreclezole also inhibited the corticosterone-induced CAT activity, but with
      lower potency, and significant effects were observed at 10 to 100 microM
      concentration. Tiagabine and stiripentol showed less potent inhibitory effect on
      functional activity of glucocorticoid receptors (GR). In contrast, topiramate and
      lamotrigine (3-100 microM) failed to affect the corticosterone-induced gene
      transcription. These data indicate that some new antiepileptic drugs and
      progabide may suppress glucocorticoid effects via the inhibition of GR-mediated
      gene transcription. In turn, attenuation of GR function could influence
      antiepileptic drug effect on seizures, neuronal degeneration and immune system
      activity.

PMID- 18048954
TI  - Role of polymorphonuclear leukocyte infiltration in the mechanism of anti
      inflammatory effect of amiodarone.
AB  - In many physiological bodily functions, and in the pathogenesis of inflammation,
      ions are exchanged between intracellular and extracellular areas. Amiodarone is a
      multiple ion channel (Ca++, Na+, K+) blocking drug, effective anti-arrhythmic
      drug, and phospholipase inhibitor. The aim of this study is to examine a role of
      polymorphonuclear leukocyte infiltration in amiodarone's anti-inflammatory effect
      on experimental paw inflammation. After rats had been assigned to groups, their
      normal right hind paw volumes were measured using a plethysmometer. Amiodarone
      (25, 50 and 100 mg/kg) and distilled water were administrated to the experimental
      and control groups, respectively, by ip route. Thirty minutes later, paw edema
      was induced in rats by subplantar injection of 0.1 ml of histamine (0.1%) to
      those paws. Subsequent volume readings for those paws were carried out at 30-min
      intervals. Results were expressed as percentages of change from the initial
      volumes. After the final measurements, the animals were killed by decapitation
      and their paw tissues were cut for pathological investigation. Amiodarone dose
      dependently decreased the paw edema (25.05, 48.71 and 74.97%), and reduced
      polymorphonuclear leukocyte infiltration in the paw tissue (55.65, 69.76 and
      84.58%). Our findings support the view that amiodarone dose-dependently exerts a
      powerful anti-inflammatory activity. This effect of amiodarone may be due to the
      activation of nitric oxide resulting from its calcium channel antagonistic
      effects, to the inhibition of phospholipase A2 and/or to a reduction in
      neutrophil movement and activation, which may reduce free radical production and
      proteolytic enzyme release.

PMID- 18048955
TI  - Prostacyclin, but not nitric oxide, is the major mediator of acetylcholine
      induced vasodilatation in the isolated mouse heart.
AB  - In many species, acetylcholine (Ach) induces coronary vasodilatation via
      endothelium-derived nitric oxide (NO). The aim of the present study was to
      examine if this rule pertains also to the coronary circulation of the mouse. We
      examined the involvement of NO and prostacyclin (PGI2) in the coronary flow
      response to Ach as compared to response to bradykinin (Bk) in hearts isolated
      from FVB or C57Bl/6 mice and perfused according to the Langendorff technique. In
      the isolated mouse heart, response to Ach consisted of two distinct phases:
      immediate, transient vasodilatation/vasoconstriction (less than 1 min) that
      differed between FVB and C57Bl/6 mice; and delayed sustained vasodilatation (up
      to 8 min) that was similar in FVB and C57Bl/6 mice. In FVB mice, the immediate
      phase of the Ach response consisted of a short-lasting vasodilatation followed by
      a vasoconstriction. In contrast, in C57Bl/6 mice, the immediate phase of the Ach
      response consisted exclusively of a short-lasting vasoconstriction. However, both
      in FVB and C57Bl/6 mice, the delayed vasodilatation was a major part of the
      coronary flow response to Ach and it was associated with an increase in 6-keto
      PGF(1 alpha) concentration in the effluent. L-NAME (5 x 10(-4) M) displayed a
      minor effect on the delayed phase of the Ach response in either mice strain. In
      turn, indomethacin (10(-6) M), but not rofecoxib (5 x 10(-6)M), completely
      inhibited the delayed phase of the Ach response and the concomitant PGI2 release.
      On the other hand, vasodilatation induced by Bk was markedly inhibited by L-NAME,
      while it was unaffected by indomethacin in FVB as well as in C57Bl/6 mice. In
      summary, in the isolated mouse heart, Ach-induced coronary flow response displays
      an unusual biphasic nature and is mediated in major part by PGI2, but not by NO.
      Thus, in the isolated mouse heart, in parallel to Bk or other agents that are
      suited for the functional assessment of NO-dependent endothelial function, Ach
      should be used to assess PGI2-dependent endothelial function.

PMID- 18048956
TI  - Nephroprotective effect of cystathionine is due to its diverse action on the
      kidney and Ehrlich ascites tumor cells.
AB  - Tumor cells, unlike normal cells, are characterized by trace cystathionase (CST)
      activity and sulfane sulfur levels. The present studies aimed to established
      whether cystathionine (CT), a substrate of cystathionase, can selectively
      influence the thiol-dependent antioxidant power of the kidney and Ehrlich ascites
      tumor (EAT). CT treatment reversed the changes in renal concentrations of non
      protein thiols (NPSH), reactive oxygen species (ROS), sulfane sulfur and
      activities of rhodanese, cystathionase and glutathione S-transferase (GST) in
      tumor-bearing mice, which returned to the level observed in healthy animals. The
      results demonstrated that CT corrected all harmful changes in the mouse kidney
      induced by EAT. In contrast, CT did not elicit such effect in EAT cells, in which
      it only increased ROS level. It indicates that CT can selectively protect the
      kidney of tumor-bearing mice against nephrotoxicity of drugs as well as restore
      biological function of sulfane sulfur. On the other hand, cisplatin (CP) did not
      affect any of the parameters under study in the kidney of tumor-bearing mice.
      Interestingly, cisplatin markedly lowered glutathione S-transferase activity and
      increased sulfane sulfur level and rhodanese activity in tumor cells. It is also
      worth noting that CP doses devoid of nephrotoxic effect in tumor-bearing mice
      could enhance cystathionine action on the kidney, causing an additional increase
      in NPSH and CST and rhodanese activity.

PMID- 18048957
TI  - Antiproliferative activity of various Uncaria tomentosa preparations on HL-60
      promyelocytic leukemia cells.
AB  - The woody Amazonian vine Uncaria tomentosa (cat's claw) has been recently more
      and more popular all over the world as an immunomodulatory, antiinflammatory and
      anti-cancer remedy. This study investigates anti-proliferative potency of several
      cat's claw preparations with different quantitative and qualitative alkaloid
      contents on HL-60 acute promyelocytic human cells by applying trypan blue
      exclusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      reduction assay (MTT). By standardization and statistical comparison of the
      obtained results pteropodine and isomitraphylline are indicated to be most
      suitable for standardization of medical cat's claw preparations.

PMID- 18048958
TI  - Synergistic protective effect of picroside II and NGF on PC12 cells against
      oxidative stress induced by H2O2.
AB  - Epidemiological studies suggest that nerve growth factor (NGF) is associated with
      a reduced risk of acute or chronic neuropathies. We studied the synergistic
      protective effect of picroside II and NGF against the oxidative stress in PC12
      cells induced by hydrogen peroxide (H2O2). The fluorescent probe CDCFH was used
      to assess the intracellular reactive oxygen species (ROS) level, and MTT assay,
      morphological observation as well as LDH leakage test were conducted to measure
      cellular injury. The H2O2-induced cytotoxicity was significantly attenuated in
      the presence of picroside II (25 microg/ml ) and NGF (2 ng/ml). Cultures with
      this combined treatment possessed decreased level of ROS while increased cell
      survival, as compared to that of picroside II or NGF alone-treated cells.
      Accordingly, it was concluded that their synergistic protective activities
      against oxidative stress in vitro were demonstrated in various aspects, including
      reversing morphological changes, enhancing the ability of cell proliferation and
      ROS scavenging. Such action supports the therapeutic potential of picroside II
      and NGF in treating nervous disorders based on their synergistic effect.

PMID- 18048959
TI  - Some drugs inhibit in vitro hydratase and esterase activities of human carbonic
      anhydrase-I and II.
AB  - In this study, we determined the in vitro inhibitory effects of ceftriaxone
      sodium, imipenem and ornidazole on hydratase and esterase activities of human
      erythrocyte carbonic anhydrase-I and II isozymes (CA I and II). Human erythrocyte
      CAI and II isozymes were purified by Sepharose-4B L-tyrosine affinity
      chromatography column with a yield of 30% and 40%, a specific activity of 920 and
      8,000 EU/mg protein, respectively. In the overall purification procedure, human
      carbonic anhydrase (hCA)-I and (hCA)-II were purified 104 and 900-fold,
      respectively. In order to determine the purity of the enzymes, SDS-PAGE was
      performed. Inhibitory effects of the drugs on hCA-I and hCA-II were determined by
      using colorimetric method for CO2-hydratase activity assay and spectrophotometric
      method for esterase activity assay. P-Nitrophenyl acetate was used as a substrate
      in the spectrophotometric esterase activity assay. The obtained IC50 values
      (inhibitor concentrations which cause 50% inhibition of in vitro enzyme activity)
      for esterase activity were 1.900, 0.008, 0.318 mM for hCA-I and 2.542, 0.0258,
      0.343 mM for hCA-II for ceftriaxone sodium, imipenem and ornidazole,
      respectively. IC50 values for CO2-hydratase activity were 0.864, 0.00354, 0.131
      mM for hCA-I and 1.118, 0.0214, 0.263 mM for hCA-II for ceftriaxone sodium,
      imipenem and ornidazole, respectively. In conclusion, ceftriaxone sodium,
      imipenem and ornidazole showed inhibitory effects on human erythrocte carbonic
      anhydrase-I and II isozyme activities under in vitro conditions.

PMID- 18048960
TI  - Effect of repeated co-treatment with imipramine and metyrapone on the behavioral
      reactivity of the central serotonin, dopamine and alpha 1-adrenergic systems in
      rats.
AB  - The aim of present study was to examine the effect of repeated co-treatment with
      imipramine and metyrapone on the development of adaptive changes in the function
      of central serotonin 5-HT1A and 5-HT2A, dopamine D2/3 and alpha 1-adrenergic
      receptors in rats. The obtained results showed that repeated co-treatment with
      imipramine (5 or 10 mg/kg) and metyrapone (50 mg/kg) (twice daily for 14 days)
      either induced more potent inhibition of the behavioral syndrome evoked by 5-HT1A
      and 5-HT2A receptor agonists (8-OH-DPAT and (+/-)DOI, respectively), or did no
      change the action of amphetamine and wuinpirole (a dopamine D2/3 agonist) or
      phenylephrine (an alpha 1-adrenergic agonist) compared to treatment with either
      drug alone. The results described in the present paper support the hypothesis
      that repeated co-treatment with imipramine and metyrapone may possess more
      effective antidepressant activity than the treatment with imipramine alone, and
      that, among other mechanisms, 5-HT1A- and 5-HT2A (but not dopamine D2/3- or alpha
      1-adrenergic) receptors may also play some role in this effect.

PMID- 18048961
TI  - Activation of the NMDA/glutamate receptor complex antagonizes the NMDA antagonist
      induced antidepressant-like effects in the forced swim test.
AB  - The antidepressant activity of NMDA receptor antagonists has been demonstrated,
      and their mechanism of action was based on the assumption of their selectivity
      for the NMDA receptor only. However, no direct evidence for the NMDA receptor
      role in this activity was demonstrated. Now, in order to prove the NMDA pathway
      of antidepressant-like action of the NMDA antagonists in the mouse forced swim
      test (FST) we examined if antidepressant activity of NMDA receptor antagonists is
      mediated by NMDA receptors and whether the activation of different modulatory
      sites of the NMDA receptor complex influence the action of the antagonists of
      different sites of NMDA receptor. In our study, we used two NMDA ligands:
      competitive NMDA glutamate site antagonist CGP 37849, and glycineB antagonist L
      701,324; both at doses found to be effective in the FST. The antidepressant-like
      activity of the compounds was abolished by the N-methyl-D-aspartic acid (NMDA) or
      by D-serine co-treatment. Ligands at the doses active in the FST did not alter
      locomotor activity. The present study indicates the major role of the
      NMDA/glutamate pathway in the antidepressant-like activity of NMDA antagonists in
      the mouse FST.

PMID- 18048962
TI  - Nitric oxide modulates the amphetamine effect on [3H]glucose uptake in the brain
      of rats prenatally exposed to lead.
AB  - Glucose is the main source of energy for the central nervous system (CNS). In
      this study, we examined the effects of the psychostimulant amphetamine (AMPH) and
      the neuronal mediator nitric oxide (NO) on [3H]glucose uptake in the brain of
      adult rats that had been prenatally exposed to lead. Lead [Pb(CH3COO)2 . 3H2O;
      250 ppm] was added to the drinking water of pregnant Wistar rats for the duration
      of pregnancy. On the day of parturition, lead was discontinued as an additive in
      the drinking water. Offspring remained ith dams for 21 days. The control group
      consisted of rats that consumed water without lead. In adulthood, male offspring
      from both groups (lead-exposed and control) were pretreated with 7-nitroindazole
      (nNOS blocking agent) (10.0 mg/kg ip) or saline (1.0 ml/kg ip), 30 min before
      AMPH (1.0 mg/kg ip). After another 30 min, and 15 min before termination, all
      rats were injected with 6-[3H]-D-glucose (500 muCi/kg ip). Brain specimens were
      taken (striatum, frontal cortex, hippocampus, and thalamus with hypothalamus, and
      pons with medulla oblongata) for determination of radioactivity in a liquid
      scintillation counter. We found that lead did not alter [3H]glucose uptake in
      brain regions studied (with exception of frontal cortex) but that AMPH increased
      [3H]glucose uptake in the striatum, frontal cortex and hippocampus, and that the
      AMPH effect was lessened in the hippocampus of lead-exposed rats. Moreover, the
      AMPH effect on [3H]glucose uptake in the frontal cortex, hippocampus, thalamus
      with hypothalamus and pons of control rats was potentiated by 7-NI pretreatment.
      Similar effect was observed in lead-intoxicated rats (striatum, frontal cortex
      and hippocampus). These results indicate that NO modulates AMPH-induced
      [3H]glucose uptake in the brain of rats prenatally exposed to lead.

PMID- 18048963
TI  - The activity of cytochrome P450 CYP2B in rat liver during neuroleptic treatment.
AB  - The aim of the present study was to investigate the influence of classic and
      atypical neuroleptics on the activity of rat CYP2B measured as a rate of 16 beta
      hydroxylation of testosterone. The reaction was studied in control liver
      microsomes in the presence of neuroleptics, as well as in microsomes of rats
      treated intraperitoneally for one day or two weeks (twice a day) with
      pharmacological doses (mg/kg) of the drugs (promazine, levomepromazine,
      thioridazine and perazine, 10 each; chlorpromazine 3; haloperidol 0.3;
      risperidone 0.1; sertindole 0.05), in the absence of the neuroleptics in vitro.
      ome of the neuroleptics added in vitro to control liver microsomes decreased the
      activity of CYP2B. The obtained Ki values indicated that thioridazine was the
      most potent inhibitor of the studied reaction (Ki = 26 microM). The inhibitory
      effects of chlorpromazine, perazine and sertindole were moderate (Ki = 45-75
      microM), while promazine, haloperidol, levomepromazine, and risperidone were
      rather weak inhibitors of CYP2B activity (Ki = 125-225 microM, respectively).
      After a one-day (i.e. 24 h) exposure of rats to the investigated neuroleptics,
      the decreased CYP2B activity was observed after haloperidol, risperidone and
      sertindole. All the investigated neuroleptics did not produce any significant
      effect on CYP2B activity when administered in vivo for two weeks. Considering
      relatively high pharmacological/therapeutic doses and liver concentrations of
      phenothiazines, it seems that the direct inhibitory effect of those neuroleptics
      with Ki values below 100 microM found in vitro (thioridazine, chlorpromazine,
      perazine), as well as indirect effects produced by one-day treatment with
      haloperidol, risperidone or sertindole may be of some physiological,
      pharmacological or toxicological importance in vivo.

PMID- 18048964
TI  - Effect of gas phase and particulate phase of cigarette smoke on salivary
      antioxidants. What can be the role of vitamin C and pyridoxine?
AB  - The effect of smoking is in our days a serious global public health problem of
      major concern. Incidence of oral squamous cell carcinoma (SCC) in cigarette
      smokers is four to seven times higher than in nonsmokers. There is a constant and
      direct attack of various cigarette smoke constituents on the oral epithelial
      cells, which gradually accumulate and cause malignant transformation. Saliva is
      the first biological fluid that encounters inhaled cigarette smoke (CS). We have
      studied the influence of CS on salivary antioxidant capacity, uric acid, amylase
      and LDH (lactate dehydrogenase). In our study both, gas and particulate phase of
      CS were tested separately, and possible antioxidant effect of pyridoxine on
      salivary components was examined. Our results indicate that exposure to both, gas
      and particulate phase of CS caused a statistically significant decrease in
      salivary uric acid, LDH and amylase activity. We have also studied the effect of
      vitamin C (10 mg/dl) and vitamin B6 (1 mM) during incubation of saliva in the
      presence of CS. The addition of vitamin C had a significant (p < 0.05) protective
      effect on salivary uric acid level (0.25 +/- 0.12 for saliva incubated with gas
      phase of CS vs. 0.65 +/- 0.12 for saliva incubated with gas phase of CS in the
      presence of vitamin C). Vitamin C was not able to maintain/restore the original
      uric acid level. In the presence of the gas phase, pyridoxine had no protective
      effect, neither on salivary uric acid level nor on the FRAP activity of saliva.
      The purpose of our study was to discover a connection between the level of
      antioxidants in saliva in the presence of the two components of CS. Our results
      show that salivary antioxidant system is significantly and distinctly affected by
      both gas and particulate phase of CS and suggest that an adequate intake of
      antioxidants may help smokers to avoid CS-induced oxidative damage and to prevent
      degenerative diseases.

PMID- 18048965
TI  - The diagnostic efficacy of urinary TGF-beta1 and VEGF in bladder cancer:
      comparison with voided urine cytology.
AB  - The purpose of this study was to evaluate the diagnostic efficacy of urinary
      transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth
      factor (VEGF) in comparison with voided urine cytology in the detection of
      bladder cancer. This study included 120 patients with bladder cancer, 54 patients
      with benign urological disorders and 55 healthy volunteers. Urine supernatant was
      used for estimation of TGF-beta1 and VEGF by ELISA. VEGF was detected by Western
      blot (WB) analysis in the urine supernatant of randomly selected bladder cancer
      patients. The urine sediment was used for cytology. There was a statistically
      significant difference in the median levels of TGF-beta1 (P=0.002) and VEGF
      (P=0.000) between the control, benign and malignant groups. The concordance rate
      of VEGF ELISA with VEGF WB was 96.3%. The overall sensitivity and specificity
      were 70.8% and 90.8% for voided urine cytology, 71.6% and 59.6% for TGF-beta1,
      and 76.7% and 61.5% for VEGF. The combined use of voided urine cytology with TGF
      beta1 and VEGF improved the sensitivity up to 94.9%, although it lowered
      specificity to 62.0%. There was a significant association between positivity rate
      of TGF-beta1 and positive urine cytology samples (P=0.023). Median level and
      positivity rate of VEGF were significantly associated with early stage (I, II) of
      bladder carcinoma (P=0.01 and 0.025, respectively). Our data indicate that
      urinary TGF-beta1 and VEGF had higher sensitivities compared to voided urine
      cytology. Moreover, the combined sensitivity of voided urine cytology with TGF
      beta1 and VEGF together was higher than sensitivity of voided urine cytology
      alone in detection of bladder cancer.

PMID- 18048966
TI  - Soluble mesothelin-related peptides (SMRP) - high stability of a potential tumor
      marker for mesothelioma.
AB  - SMRP (soluble mesothelin-related peptides) is a promising marker for detection of
      malignant mesotheliomas (MM) in serum that has not yet been validated in
      appropriate epidemiological studies. Field studies might not always provide
      optimal conditions for storage and transport of samples, and follow-up studies
      have to rely on sample integrity. Proper validation of the marker would require
      sufficient stability of the antigen and robustness of the assay. SMRP
      concentrations were evaluated in serum samples of 98 healthy donors, using the
      MESOMARK ELISA kit. The SMRP distribution in the healthy study population was
      determined and biological and pre-analytical variations were examined regarding
      their influence on SMRP concentrations. For diagnostic decisions a best
      statistical and unbiased cut-off between 1.5 and 1.6 nmol/L was determined (95th
      percentile). No age- or gender-specific differences could be observed. SMRP
      exhibits excellent stability regarding short-term storage, long-term storage, and
      repeated freeze/thaw cycles. Scientific studies as well as real life applications
      that employ SMRP would not be limited by sample stability issues.

PMID- 18048967
TI  - High serum TIMP-1 correlates with poor prognosis in breast carcinoma - a
      validation study.
AB  - A number of studies have demonstrated that high tumor tissue levels of tissue
      inhibitor of metalloproteinases-1 (TIMP-1) are associated with a poor prognosis
      in breast cancer, suggesting that TIMP-1 could be a valid prognostic marker in
      this disease. Recently, our laboratories have presented results showing that TIMP
      1 also carries prognostic information when measured in serum. This is an
      important finding, since serum is a much more preferable material compared with
      tumor tissue extracts. The aim of the present study was to validate the previous
      results concerning the prognostic value of TIMP-1 in serum obtained
      preoperatively from 68 patients with primary breast cancer. This was done by
      measuring the same serum samples as in the previous study but in a different
      laboratory using a different ELISA assay. We confirmed that patients with the
      highest serum levels of TIMP-1 (> 197.7 ng/ml) had significantly shorter disease
      specific survival compared with patients with low serum TIMP-1 levels. In the
      group of node-negative patients, 53% of the patients with high levels of TIMP-1
      survived after 10 years of follow-up compared to 92% of the patients with low
      levels. This study thus confirms the reproducibility across laboratories of the
      results concerning the prognostic value of TIMP-1 in serum. We also investigated
      whether measurements of the specific fraction of uncomplexed TIMP-1 improved the
      prognostic value of TIMP-1 in serum, as has been shown to be the case for tumor
      tissue extracts. However, including information of the level of uncomplexed TIMP
      1 did not seem to provide additional prognostic information to that already
      provided by total TIMP-1.

PMID- 18048969
TI  - Detection of the JAK2V617F mutation by asymmetric PCR and melt curve analysis.
AB  - The chronic myeloproliferative disorders (CMPDs) are a heterogeneous group of
      clonal hematopoietic diseases characterized by production of increased numbers of
      mature leukocytes, erythrocytes, and/or platelets. Clinically these disorders are
      often insidious in onset, produce nonspecific thrombotic or hemorrhagic
      complications, and can be easily confused with a variety of benign, reactive
      conditions. Thus, confirming a CMPD can be difficult as it is often a diagnosis
      of exclusion. The recently identified JAK2(V617F) mutation is frequently present
      in the classic CMPDs polycythemia vera, essential thrombocythemia, and chronic
      idiopathic myelofibrosis. JAK2(V617F) determination has proven to be a useful
      diagnostic tool in patients with some clinical features suggestive for a CMPD,
      and may have benefit as a way to monitor known disease. There are several
      published molecular assays for the JAK2(V617F) target, of variable sensitivity
      and technical complexity, many of which are not easily replicated in a typical
      clinical laboratory. We present a robust, sensitive PCR/melt curve assay for the
      JAK2(V617F) mutation which uses the widely available Roche LightCycler platform,
      and is thus applicable to many clinical molecular laboratories.

PMID- 18048970
TI  - Association between VEGF expression in tumour-associated macrophages and elevated
      serum VEGF levels in primary colorectal cancer patients.
AB  - OBJECTIVE: Angiogenesis is stimulated by angiogenic factors released by tumour
      cells, though other cells, such as tumour-associated macrophages (TAMs), also
      contribute towards increasing the angiogenic process in colorectal cancer (CRC).
      The aim of this study was to determine in CRC patients the contribution of
      vascular endothelial growth factor (VEGF) expression in TAMs and tumour cells
      towards circulating VEGF levels, their association with p53 expression and
      microvascular density (MVD), and their prognostic value. METHODS:
      Immunohistochemical techniques were used to identify TAMs and p53 protein, and to
      evaluate the VEGF expression in TAMs, MVD and tumour cells in 110 primary CRC
      patients. Serum VEGF levels were determined using an enzyme immune assay.
      RESULTS: There was a greater expression of VEGF in tumours with a positive p53
      expression than a negative stain (p<0.01). The macrophage index was not related
      to tumour VEGF secretion. No significant association was observed between serum
      VEGF levels and VEGF tumour expression, node status, histological grade, MVD or
      p53 expression. However, the patients with high values of VEGF expression in TAMs
      showed significantly higher presurgery serum VEGF levels than those patients with
      low values of VEGF expression in TAMs (p=0.021). No statistical significant
      differences in survival were found when we compared patients with high VEGF
      expression in TAMs vs low or median VEGF expression in TAMs (p=0.093). Serum VEGF
      levels were increased 6-8 hours after tumour removal (p=0.001). CONCLUSIONS: Our
      data suggest that in primary CRC, presurgery circulating VEGF levels are related
      to VEGF produced by TAMs.

PMID- 18048968
TI  - African-American and Caucasian disparities in colorectal cancer mortality and
      survival by data source: an epidemiologic review.
AB  - Over the past four decades in the United States, there has been a divergent trend
      in mortality rates between African-Americans and Caucasians with colorectal
      cancer (CRC). Rates among Caucasians have been steadily declining, whereas rates
      among African-Americans have only started a gradual decline in recent years. We
      reviewed epidemiologic studies of CRC racial disparities between African
      Americans and Caucasians, including studies from SEER and population-based cancer
      registries, Veterans Affairs (VA) databases, healthcare coverage databases, and
      university and other medical center data sources. Elevated overall and stage
      specific risks of CRC mortality and shorter survival for African-Americans
      compared with Caucasians were reported across all data sources. The magnitude of
      racial disparities varied across study groups, with the strongest associations
      observed in university and non-VA hospital-based medical center studies, while an
      attenuated discrepancy was found in VA database studies. An advanced stage of
      disease at the time of diagnosis among African-Americans is a major contributing
      factor to the racial disparity in survival. Several studies, however, have shown
      that an increased risk of CRC death among African-Americans remains even after
      controlling for tumor stage at diagnosis, socioeconomic factors, and co
      morbidity. Despite advances in treatment, improvements in the standard of care,
      and increased screening options, racial differences persist in CRC mortality and
      survival. Therefore, continued research efforts are necessary to disentangle the
      clinical, social, biological, and environmental factors that constitute the
      racial disparity. In addition, results across data sources should be considered
      when evaluating racial differences in cancer outcomes.

PMID- 18048971
TI  - Potentials of real time control, stormwater infiltration and urine separation to
      minimize river impacts: dynamic long term simulation of sewer network, pumping
      stations, pressure pipes and waste water treatment plant.
AB  - River Panke (Berlin, Germany) suffers from hydraulic peak loads and pollutant
      loads from separate sewers and combined sewer overflows (CSOs). Pumping the
      wastewater through long pressure pipes causes extreme peak loads to the
      wastewater treatment plant (WWTP) during stormwater events. In order to find a
      good solution, it is essential not to decide on one approach at the beginning,
      but to evaluate a number of different approaches. For this reason, an integrated
      simulation study is carried out, assessing the potentials of real time control
      (RTC), stormwater infiltration, storage and urine separation. Criteria for the
      assessment are derived and multi-criteria analysis is applied. Despite spatial
      limitations, infiltration has the highest potential and is very effective with
      respect to both overflows and the WWTP. Due to a high percentage of separate
      systems, urine separation has a similar potential and causes the strongest
      benefits at the WWTP. Unconventional control strategies can lead to significant
      improvement (comparable to infiltrating the water from approximately 10% of the
      sealed area).

PMID- 18048972
TI  - Dynamic optimisation of WWTP inflow to reduce total emission.
AB  - A prerequisite for an integrated control of sewer and wastewater treatment plant
      (WWTP) is a capacity driven inflow control to WWTP. This requires reliable
      information about the current status of WWTP operation and its behaviour on
      varying hydraulic, COD and nutrient loads. So far most of the proposed control
      strategies are based on hypothetical modelling studies. In this paper the
      behaviour of three large WWTPs on increased storm water loads is analysed based
      on online measurements of several years. In all cases the main limiting factors
      for an increase of load were the sedimentation processes in the secondary
      clarifier and the nitrification capacity. In one case study predictive control
      strategies have been developed observing these processes which are backboned by
      effluent control. Tests using an integrated model of sewer and WWTP demonstrate
      that inflow control on emission load varies significantly with rain intensity.

PMID- 18048973
TI  - Thermophilic anaerobic digestion in compact systems: investigations by modern
      microbiological techniques and mathematical simulation.
AB  - Thermophilic anaerobic digestion in compact systems can be an economical and
      ecological reasonable decentralised process technique, especially for rural
      areas. Thermophilic process conditions are important for a sufficient removal of
      pathogens. The high energy demand, however, can make such systems unfavourable in
      terms of energy costs. This is the case when low concentrated wastewater is
      treated or the system is operated at low ambient temperatures. In this paper we
      present experimental results of a compact thermophilic anaerobic system obtained
      with fluorescent in situ hybridisation (FISH) analysis and mathematical
      simulation. The system was operated with faecal sludge for a period of 135 days
      and with a model substrate consisting of forage and cellulose for a period of 60
      days. The change in the microbial community due to the two different substrates
      treated could be well observed by the FISH analysis. The Anaerobic Digestion
      Model no. 1 (ADM1) was used to evaluate system performance at different
      temperature conditions. The model was extended to contribute to decreased
      methanogenic activity at lower temperatures and was used to calculate energy
      production. A model was developed to calculate the major parts of energy consumed
      by the digester itself at different temperature conditions. It was demonstrated
      by the simulation study that a reduction of the process temperature can lead to
      higher net energy yield. The simulation study additionally showed that the effect
      of temperature on the energy yield is higher when a substrate is treated with
      high protein content.

PMID- 18048974
TI  - Application of enzymes in anaerobic digestion.
AB  - Owing to the very low economic value of brewer's spent grains, its utilisation
      for biogas production is very promising. The hydrolysis of ligno-cellulose is the
      rate limiting step in anaerobic digestion. Enzymatic pre-treatment promotes the
      hydrolysis of ligno-cellulose, breaking it down to lower molecular weight
      substances which are ready to be utilised by the bacteria. A cheap raw multi
      enzyme produced by a solid state fermentation (SSF) process is a good substitute
      for expensive conventional enzyme. The SSF enzyme application to spent grain has
      been investigated by carrying out enzymatic solubility tests, hydrolytic
      experiments and two-step anaerobic fermentation of spent grain. Gas chromatograph
      analysis was conducted to quantify fatty acids concentrations, while CH(4),
      CO(2), O(2), H(2) and H(2)S were measured to determine biogas quality by means of
      a gas analyser. DS, oDS, pH were also measured to analyse the anaerobic
      digestion. The result shows that enzyme application promotes the hydrolysis of
      ligno-cellulose, indicated by higher enzymatic solubility and fatty acid
      concentration in a hydrolytic bioreactor. Moreover, biogas production is also
      increased. The quality of the gases produced is also enhanced. Since the
      anaerobic digestion can be operated in a stable performance, it can also be
      concluded that SSF enzyme is compatible with anaerobic digestion.

PMID- 18048975
TI  - Anaerobic treatment of municipal wastewater using the UASB-technology.
AB  - The anaerobic treatment of municipal wastewater enables new applications for the
      reuse of wastewater. The effluent could be used for irrigation as the included
      nutrients are not affected by the treatment. Much more interesting now are
      renewable energies and the retrenchment of CO(2) emission. With the anaerobic
      treatment of municipal wastewater, not only can the CO(2) emission be reduced but
      "clean" energy supply can be gained by biogas. Most important for the
      sustainability of this process is the gathering of methane from the liquid
      effluent of the reactor, because the negative climate-relevant effect from the
      degassing methane is much higher than the positive effect from saving CO(2)
      emission. In this study, UASB reactors were used with a flocculent sludge blanket
      for the biodegradation of the carbon fraction in the wastewater with different
      temperatures and concentrations. It could be shown that the positive effect is
      much higher for municipal wastewater with high concentrations in hot climates.

PMID- 18048976
TI  - Anaerobic co-digestion of sludge with other organic wastes in small wastewater
      treatment plants: an economic considerations evaluation.
AB  - This paper deals with an economic comparison between costs and incomes in small
      wastewater treatment plants where the anaerobic co-digestion process of sludge
      and biowaste with energy recovery is operated. Plants in the size range 1,000
      30,000 persons equivalent (pe) were considered in the study: typical costs,
      comprehensive of capital and operating costs, were in the range euro69-105 per
      person per year depending on the plant size: the smaller the size the higher the
      specific cost. The incomes deriving from taxes and fees for wastewater treatment
      are generally in the range euro36-54 per person per year and can only partially
      cover costs in small wastewater treatment plants. However, the co-treatment of
      biowaste and the use of produced energy for extra credits (green certificates)
      determine a clear improvement in the possible revenues from the plant. These were
      calculated to be euro23-25 per person per year; as a consequence the costs and
      incomes can be considered comparable for wastewater treatment plants (WWTPs) with
      size larger than 10,000 pe. Therefore, anaerobic co-digestion of biowaste and
      sludge can also be considered a sustainable solution for small wastewater
      treatment plants in rural areas where several different kinds of biowaste are
      available to enhance biogas production in anaerobic reactors.

PMID- 18048977
TI  - The impact of increasing energy crop addition on process performance and residual
      methane potential in anaerobic digestion.
AB  - In a full-scale agricultural biogas plant, the changes in process performance
      connected with the increasing energy crop addition were monitored. The substrates
      applied were pig manure, solid energy crops and agricultural residues. During the
      study, the organic loading rate and the volume-related biogas productivity were
      doubled to 4.2 kg VS/(m(.3)d) and 2.83 Nm(3)/(m(3).d) respectively, by means of
      increasing the energy crop ratio in the feedstock to 96.5% (volatile solids).
      This resulted in an increase of the electrical capacity on a level twice as high
      as before. At the same time, methane yield and organic degradation rate decreased
      slightly to 0.35 Nm(3)/kg VS(added) and 87.4%, respectively. The strongest impact
      observed was on the transfer of partly degraded organic material into the
      digestate storage and with this, an increase of the residual methane potential of
      the digestate. A maximum theoretical methane load in the digestate of 14.4%
      related to total methane production of the biogas plant was observed. This
      maximum level could be reduced to 5.5%.

PMID- 18048978
TI  - Small wastewater treatment plants in mountain areas: combination of septic tank
      and biological filter.
AB  - Research work has been carried out for more than 20 years by Eparco and the
      University of Montpellier (France) on the application of biological wastewater
      treatment processes for small communities. This research has led to a new process
      which is particularly suitable for remote populations, taking into account
      several specificities such as as the seasonal fluctuations in the population, the
      accessibility of the site, the absence of a power supply on site, the reduced
      area of land available and the low maintenance. Thus, the process, which combines
      a septic tank operating under anaerobic conditions and a biological aerobic
      filter, is a solution for wastewater treatment in mountain areas. This paper
      presents the process and three full-scale applications in the region of the Alps.

PMID- 18048979
TI  - An evaluation of applying existing bioretention sizing methods to cold climates
      with snow storage conditions.
AB  - Eight of the current sizing and design methods proposed for bioretention
      facilities were evaluated for rainfall runoff and snow storage volumes for a
      costal cold climate in Trondheim, Norway. The RECARGA bioretention infiltration
      model was used to compare the performance of the methods using 30 months of
      observed data from a pilot scale bioretention box. The surface areas, total
      ponding time, number and duration of overflow events, and snow storage volumes
      were compared. It was found that even in a costal cold climate with several
      intermittent melt cycles die snow storage requirements were an important design
      parameter, and if more than 25% of the total snow volume should stored this
      became the deciding design parameter.

PMID- 18048980
TI  - The influence of temperature on nutrient treatment efficiency in stormwater
      biofilter systems.
AB  - Nutrients can cause eutrophication of natural water bodies. Thus, urban
      stormwater which is an important nutrient source in urbanised areas has to be
      treated in order to reduce its nutrient loads. Biofilters which use soil filter
      media, biofilms and plants, are a good treatment option for nutrients. This paper
      presents the results of a biofilter column study in cold temperatures (+2 degrees
      C, +8 degrees C, control at +20 degrees C) which may cause special problems
      regarding biofilter performance. It was shown that particle-bound pollutants as
      TSS and a high fraction of phosphorus were reduced well without being negatively
      influenced by cold temperatures. Nitrogen, however, was not reduced; especially
      NO(x) was produced in the columns. This behaviour can be explained with both
      insufficient denitrification and high leaching from the columns.

PMID- 18048981
TI  - Hydraulic performance of biofilters for stormwater management: first lessons from
      both laboratory and field studies.
AB  - In order to improve knowledge on stormwater biofiltration systems, the Facility
      for Advancing Water Biofiltration (FAWB) was created at Monash University in
      Melbourne, Australia. One of the aims of FAWB is to improve hydraulic performance
      of biofilters, given that there are numerous cases of infiltration devices
      failing after a few years of operation. Experiments were conducted in the field
      to evaluate the performance of existing systems, and in the lab to understand the
      factors that influence hydraulic behavior over time. The field experiments show
      that 43% of tested systems are below nominal Australian guidelines for hydraulic
      conductivity. The preliminary lab results show a decrease in hydraulic
      conductivity during the first weeks of operation (mu=66% reduction), although
      most remain within acceptable limits. Influences of the size of the biofilter
      relative to its catchment and the importance of the type of media, on the
      evolution of hydraulic conductivity, are examined.

PMID- 18048982
TI  - Membrane filtration for particles removal after ozonation-biofiltration.
AB  - With the process combination Ozonation-Biofiltration-Membranefiltration (the OBM
      process) an average removal of 63% for UV-absorbance (UV(254)), 79% for color,
      and 28% for DOC was obtained treating NOM containing surface water. In this
      paper, focus has been made on the removal of particles after the ozonation and
      biofiltration treatment steps, using a submerged hollow fiber ultrafiltration
      membrane reactor. For this purpose the membrane performed adequately. The
      ultrafiltration step did not have a significant impact on the removal of color,
      UV(254), and DOC. However, the SS and the heterotrophic plate count (HPC) was
      almost completely removed, and the turbidity was reduced by 65% by the membrane
      filtration, even at very high fluxes. Fouling occurred during operation, and
      operational factors of both the ozonation/biofiltration and the membrane reactor
      were important for controlling this. The experiments at pH 6.5 gave a higher
      permanent fouling than at pH 8.5, which was caused by the different oxidation
      pathways and consequently by the change in size and hydrophobicity of the by
      products. On the other hand, the reversible fouling was less important at low pH.
      The mechanical cleaning was efficient, however, it seemed that the air scouring
      participated to the formation of submicron particles which favored the fouling.

PMID- 18048983
TI  - Effects of floc and bubble size on the efficiency of the dissolved air flotation
      (DAF) process.
AB  - Dissolved air flotation (DAF) is a method for removing particles from water using
      micro bubbles instead of settlement. The process has proved to be successful and,
      since the 1960s, accepted as an alternative to the conventional sedimentation
      process for water and wastewater treatment. However, limited research into the
      process, especially the fundamental characteristics of bubbles and particles, has
      been carried out. The single collector collision model is not capable of
      determining the effects of particular characteristics, such as the size and
      surface charge of bubbles and particles. Han has published a set of modeling
      results after calculating the collision efficiency between bubbles and particles
      by trajectory analysis. His major conclusion was that collision efficiency is
      maximum when the bubbles and particles are nearly the same size but have opposite
      charge. However, experimental verification of this conclusion has not been
      carried out yet. This paper describes a new method for measuring the size of
      particles and bubbles developed using computational image analysis. DAF
      efficiency is influenced by the effect of the recycle ratio on various average
      floc sizes. The larger the recycle ratio, the higher the DAF efficiency at the
      same pressure and particle size. The treatment efficiency is also affected by the
      saturation pressure, because the bubble size and bubble volume concentration are
      controlled by the pressure. The highest efficiency is obtained when the floc size
      is larger than the bubble size. These results, namely that the highest collision
      efficiency occurs when the particles and bubbles are about the same size, are
      more in accordance with the trajectory model than with the white water collector
      model, which implies that the larger the particles, the higher is the collision
      efficiency.

PMID- 18048984
TI  - Evaluation of floc strength by morphological analysis and PDA online monitoring.
AB  - This paper established a method for the evaluation of floc strength by
      morphological analysis and PDA online monitoring. Theoretically, the binding
      force of a floc can be expressed as B=k(1)d(2Df/3), where k(1) is a coefficient,
      d is floc size and D(f) is the fractal dimension of the floc. In order to
      calculate the binding force under a given flocculation condition, a jar test was
      conducted and d and D(f) were measured by image analysis. A shear force was
      exerted on the grown flocs by introducing the flocculated suspension through a
      transparent tube where the velocity gradient value of the flow could be
      accurately controlled. As the tube was connected with a particle dispersion
      analyzer (PDA), the condition of floc breakage was online monitored and the
      critical condition was identified by analyzing the PDA outputs (FI curves). The
      binding force coefficient k(1) could thus be determined, and the binding force B
      which represented the floc strength was evaluated. The validity of this method
      was proved by a series of experiments using aluminium sulphate as coagulant for
      the flocculation of humic substances.

PMID- 18048985
TI  - Highway filter drain waste arisings: a challenge for urban source control
      management?
AB  - Essential maintenance activities on highway BMP drainage controls involve
      refurbishment of filter (French) drains which can generate substantial amounts of
      "controlled waste". An innovative procedure for their re-instatement is described
      which offers a more sustainable option for filter drain/trench management. The
      quality classification of these waste arisings is problematical and it is
      difficult to reliably identify the risks posed by such materials and the most
      effective forms of management and disposal options.

PMID- 18048986
TI  - Runoff and infiltration characteristics of pavement structures--review of an
      extensive monitoring program.
AB  - The stormwater runoff and infiltration performance of permeable pavements has
      been systematically evaluated within an intensive monitoring program. The primary
      objective of the investigation was to generate a broad database, which enables
      the development of an advanced simulation module for urban drainage modelling.
      Over 160 field and lab scale experiments have been completed and analyzed for
      surface runoff and infiltration characteristics. The test series include several
      pavement types under various boundary conditions such as diverse precipitation
      impacts, varying surface slope and layer construction as well as different stages
      of surface clogging and several base and subgrade layer characteristics. The
      results represent a reliable and comprehensive database that allows profound
      conclusions and substantial recommendations.

PMID- 18048987
TI  - Occurrence and fate of organic pollutants in combined sewer systems and possible
      impacts on receiving waters.
AB  - Selected organic pollutants are classified based on an intensive literature
      survey. Two wastewater parameters (COD and ammonium) and six selected organic
      pollutants (polycyclic aromatic hydrocarbons (PAH), diethylhexylphthalate (DEHP),
      estradiol (E2), ethinylestradiol (EE2), ethylenediamine tetraacetic acid (EDTA)
      and nitrilo triaceticacid (NTA)) are specified. As a result, for the first time
      representative concentrations in dry weather flow, surface runoff and effluent of
      wastewater treatment plants (WWTPs) in combined sewer systems (CSS) are stated.
      The second part of the paper presents a first estimation of main emission out of
      a combined sewer system and possible receiving water impacts in terms of (1)
      annual discharged loads calculated by pollution load simulations in a
      hypothetical catchment and (2) concentrations calculated in combined sewer
      overflows (CSO) discharges and resulting receiving water concentrations.

PMID- 18048988
TI  - Enhanced separation of water quality parameters in the DAF (Dissolved Air
      Flotation) system using ozone.
AB  - Dissolved Air Flotation (DAF) has been used in water and wastewater treatment
      because it has an excellent separation capability. It was found that the
      separation capability of the DAF system could be even more enhanced by ozone.
      Ozone was applied as a substitute for air in the DAF system, so that the system
      was named as the DOF (Dissolved Ozone Flotation) system. Ozone not only enhances
      coagulation as is well known, but also provides larger micro-bubble volume
      because the solubility of ozone in water is much higher than that of air. Ozone
      enhanced the separation rate of SS by 13.6%, and turbidity by 21% in the DOF
      system compared to the DAF system. T-P was also removed 7.7% more in the DOF
      system. 41.5% of color and 7.4% of COD(Cr) were enhanced in their removal rate.
      Coliform and heterotrophic bacteria were removed 54% and 57.3% more in the DOF
      system. Separation capability of the DOF system was greatly enhanced for most of
      the water quality parameters because ozone provides strong oxidation power with
      large volume of micro-bubbles.

PMID- 18048989
TI  - Application of the flexible fiber filter module (3FM) filter to sea water
      filtration.
AB  - The new 3FM filter (Flexible Fiber Filter Module), implementing very fine nylon
      fibers as filtration media was tested at pilot scale for the first time on sea
      water. The objective was to improve the quality of raw sea water to produce water
      for injection into offshore wells for extraction purposes on oil-bearing fields.
      Particles larger than 5 microm must be removed from the water of injection to
      avoid clogging at the point of injection into the porous rock. The purpose of the
      tests carried out over several months at Palavas Les Flots (France) was to
      specify the optimal operating conditions of the 3FM filter. Various coagulants
      and combinations of reagents were tested at velocities ranging between 50 and 200
      m(3)/m(2)/h (ground filtration velocity). On raw sea water of about 1 NTU
      turbidity and at velocities of 100 m(3)/m(2)/h, the filtered water contained
      about 300 particles per mL larger than 1 microm, and less than 15 particles
      larger than 5 microm per mL. The filter runs range from one hour to few hours,
      variable according to the raw water turbidity, the reagent dosing rate and the
      filtration velocity. Backwashes, a succession of air scours at high air flow
      rates combined with water phases, the total duration of which did not exceed 1
      minute, were shown to be efficient during the three months testing period. 3FM
      filter performance was promising for many other possible applications.

PMID- 18048990
TI  - Nonclassic steroid 21-hydroxylase deficiency due to a homozygous V281L mutation
      in CYP21A2 detected by the neonatal mass-screening program in Japan.
AB  - Since 1989, neonatal mass screening for congenital adrenal hyperplasia (CAH) has
      been carried out in Japan. The mass screening has detected not only the patients
      with the classic form of steroid 21-hydroxylase deficiency (21-OHD), but also
      those with the nonclassic (NC) form of 21-OHD, and the molecular basis in these
      patients has been elucidated. However, the homozygous V281L mutation in CYP21A2,
      the common mutation in the NC form in Caucasians, has not been described in
      Japanese patients, implying at least two possibilities; 1) the V281L mutation
      itself might be very rare in Japanese, and 2) nonclassic 21-OHD patients bearing
      the V281L mutation might be barely detectable by the mass-screening program,
      hence overlooked in Japan. In the present study, we describe a Brazilian girl
      with the NC form of 21-OHD, who was pointed out to have mildly elevated 17 alpha
      hydroxyprogesterone in blood by the mass screening in Japan. Genetic analysis
      revealed that the patient was homozygous for the V281L mutation, and that the
      parents were heterozygous for the V281L mutation. Thus, the NC patients due to
      the homozygous V281L mutation can be detectable by the mass-screening program for
      CAH in Japan, and further accumulation and analysis of the NC patients should
      elucidate the frequency of the V281L allele in Japan.

PMID- 18048991
TI  - Divided-dose administration of miglitol just before and 15 minutes after the
      start of a meal smoothes postprandial plasma glucose excursions and serum insulin
      responses in healthy men.
AB  - We recently demonstrated that administration of miglitol at 15 min after the
      start of a meal decreased the area under the curve (AUC) of plasma glucose,
      similar to the observation following its administration just before a meal. This
      finding prompted us to examine whether a divided-dose regimen of miglitol might
      attenuate postprandial glucose excursions even more effectively. We, therefore,
      examined several schedules of miglitol administration in 15 healthy men. Miglitol
      was administered by four different schedules in each subject (control: no
      miglitol, intake 1: drug administered just before a meal (50 mg); intake 2: drug
      administered at 15 min after the start of a meal (50 mg); intake 3: drug
      administered in two divided doses: just before a meal (25 mg) and at 15 min after
      the start of a meal (25 mg). The AUC of glucose excursions, defined as increment
      above the fasting glucose level, (AUC(0-180 min) of glucose excursions) was
      significantly reduced as compared with that in the control condition after
      miglitol administration by intake schedule 3, while this parameter showed a
      tendency towards decrease after the drug administration by intake schedules 1 and
      2. The AUC(0-180 min) of the serum insulin level was also significantly decreased
      for all the intake schedules of miglitol, as compared with that in the control
      condition. Thus, administration of miglitol in two divided doses appeared to be
      the most suitable for obtaining effective regulation of postprandial glucose
      excursions in healthy men. This result may suggest that the divided-dose
      administration regimen may also be effective in diabetic patients.

PMID- 18048992
TI  - Simultaneous presentation of thyrotoxicosis and diabetic ketoacidosis resulted in
      sudden cardiac arrest.
AB  - Although many cases of simultaneous presentation of thyrotoxicosis (thyroid
      storm) and diabetic ketoacidosis have been reported, it is a clinically unusual
      situation and remains a diagnostic and management challenge in clinical practice.
      The diagnosis of diabetic ketoacidosis or thyrotoxicosis may be masked leading to
      serious complications. We report two patients with simultaneous thyrotoxicosis
      and diabetic ketoacidosis resulted in sudden cardiac arrest, emphasizing early
      recognition and prompt treatment when these two disease are presented
      concomitantly.

PMID- 18048994
TI  - [Lifestyle related diseases in elderly].

PMID- 18048993
TI  - A case of magnesium deficiency associated with insufficient parathyroid hormone
      action and severe osteoporosis.
AB  - The relationship between osteoporosis and magnesium (Mg) deficiency is still
      controversial. Here we report a case of an 82-year-old woman with a giant
      adenomatous goiter and severe osteoporosis with multiple vertebral fractures,
      whose clinical course indicated that her osteoporosis was probably due to Mg
      deficiency. She visited our hospital for treatments of tetany. Laboratory data
      showed the existence of hypomagnesemia, hypocalcemia, hypokalemia, vitamin D
      deficiency, and slightly elevated intact PTH. Intravenous administration of Mg
      not only improved these electrolyte abnormalities but also increased serum levels
      of intact PTH, bone formation markers, 1,25-dihydroxyvitamin D, as well as bone
      resorption markers in the urine, and lowered urinary phosphate reabsorption.
      Hypomagnesemia on admission seemed to arise from long-lasting poor food intake
      and malnutrition, because it improved after the disappearance of dysphagia with a
      goiter resection. After the operation, BMD values at the lumbar spine and femoral
      neck obviously increased during 6 months of Mg supplementation without any
      specific therapies for osteoporosis. Mg deficiency in this case seemed to cause
      impaired secretion of PTH from the parathyroid and the refractoriness of bone and
      kidney to the hormone, which led to the suppression of both bone remodeling and
      renal vitamin D production. These processes were probably linked to her severe
      osteoporosis, which was reversed by Mg supplementation.

PMID- 18048995
TI  - [Medical care in local community of Hokkaido in the drastic change of medical
      treatment system].

PMID- 18048996
TI  - [Parkinsonism].

PMID- 18048997
TI  - [Lacunar infarcts in the elderly with special reference to their historical
      aspects].

PMID- 18048998
TI  - [Clinical remarks of diabetes mellitus in the elderly].

PMID- 18048999
TI  - [Management of hypertension in the elderly].

PMID- 18049000
TI  - [Osteoporosis in the elderly].

PMID- 18049001
TI  - [Clinical aspects of cardiac failure in the elderly people].

PMID- 18049002
TI  - [Clinical management of the aged patients with COPD].

PMID- 18049003
TI  - [Treatment of elderly patients with hematological diseases].

PMID- 18049004
TI  - [Prevention of the falls in the elderly].

PMID- 18049005
TI  - [The role of a memory clinic in regional supporting system for mild dementia
      patients and caregivers].

PMID- 18049006
TI  - [Management of colorectal cancer in elderly patients over 80 years old].
AB  - AIM: The incidence of colorectal cancer is increasing. Surgery and chemotherapy
      for elderly patients are also increasing. We evaluated the characteristics of
      elderly colorectal cancer to clarify issues related to surgical therapy for
      elderly patients. METHOD: We studied 67 patients (38 men, 29 women) over 80 years
      old on whom we operated for colorectal cancer from 1990 to 2004. We compared them
      with 130 patients aged from 70 to 74 who were operated on in the same period,
      examining clinicopathological factors, operative methods, preoperative morbidity,
      postoperative complications, chemotherapy and postoperative survival ratio.
      RESULTS: In the elderly patients aged over 80, the rate of Dukes' B was high,
      whereas the rate of Dukes' A was high in patients aged from 70 to 74. No
      significant differences were observed in operative methods for colon cancer but
      Hartmann's operation and transanal local excision were frequent for rectal cancer
      in patients aged over 80. The rate of lymph node dissection was low in patients
      aged over 80 with rectal cancer. A significant difference was observed in lymph
      node dissection of rectal cancer between patients aged over 80 and those aged
      from 70 to 74, but there was no significant difference in curative ratio.
      Preoperative morbidity were recognized in 76% of patients aged over 80.
      Postoperative complications occurred in 51% of patients aged over 80. There were
      many cases showing delirium, but no differences in other complications between
      patients aged over 80 and those aged from 70 to 74. There was no operative
      mortality in patients aged over 80. CONCLUSION: Even elderly patients can
      anticipate safe operations without postoperative complications or decreased
      quality of life, if the appropriate operative procedure is selected with regard
      to their general condition.

PMID- 18049007
TI  - [Differences in cardiac management and in-hospital mortality between elderly
      patients with and without dementia after acute myocardial infarction: findings
      from TAMIS data].
AB  - AIM: In the United States, a study has shown that dementia is a significant
      factor negatively associated with medical treatment. Because the increasing
      number of the elderly has resulted in cause a rise in patients with dementia or
      acute myocardial infarction (AMI), or both, we need to know the differences in in
      hospital mortality between patients with or without dementia in patients with
      AMI. METHODS: We used data from 13 acute care hospitals including in the data
      from the Tokai Acute Myocardial Infarction Study (TAMIS), a retrospective study
      of all patients admitted to these hospitals from 1995 to 1997 with a diagnosis of
      AMI. We abstracted the baseline and procedural characteristics from detailed
      chart reviews. A total of 22 patients with dementia and 1,030 with no dementia
      who were aged 65 and over were included in the present study, and were divided
      into two groups according to their diagnosis of dementia. We compared the
      baseline and procedure characteristics and clinical outcomes between the two
      groups. RESULTS: Patients with dementia were older and more likely to have either
      a lower body mass index score or ADL impairment. As for medical history, patients
      with dementia were more likely to have a history of cerebrovascular disease, and
      less likely to have a history of angina or smoking. Before and after
      multivariable adjustment, no significant difference was found in in-hospital
      mortality between patients with or without dementia. CONCLUSIONS: Our study
      demonstrates that AMI elderly patients with dementia were not less likely to be
      undertreated and did not have a higher in-hospital mortality rate than non
      dementia patients.

PMID- 18049008
TI  - [An overview and prospect of demented outpatient care in a department of
      geriatric medicine: report based on statistical review of the memory clinic at
      the geriatric outpatient unit of the Nagoya University Hospital].
AB  - AIM: Although there are many reports regarding the status of memory clinics in
      Japan, most are from the clinical departments of psychiatry or neurology, and
      there are few from the geriatric outpatient clinics. This study aimed to review
      the status of the memory clinic at the geriatric outpatient unit of a university
      hospital and also to compare the results with other reports. METHODS: Patient
      records of the memory clinic at the geriatric outpatient unit of the Nagoya
      University Hospital between January 2000 and June 2006, which included clinical
      information and neuropsychological profiles were extensively reviewed for
      statistical analyses. Of the patients who first visited the memory clinic between
      January 2004 and June 2006, prior written consent are obtained from 232
      outpatients, among which 223 individuals who had intact sets of data were
      subjected to detailed analyses. RESULTS: During the period investigated, we had a
      total of 778 visits by 577 patients. The characteristics of patients were: age:
      74.5+/-8.3 years; MMSE: 23.8+/-4.7; education year: 10.7+/-2.9. Clinical profiles
      of the patients who visited during the most recent 2.5 years were as follow:
      cognitively normal, 8.1%; dementia of Alzheimer's type, 45.3%; vascular type,
      5.4%; mixed type, 2.2%; frontotemporal dementia, 3.1%; mild cognitive impairment,
      15.7%, and others. CONCLUSION: Compared with previous reports from other
      institutions, we observed that the visitors to our geriatric memory clinic had a
      relatively higher educational background with earlier stages of dementing
      disorders, which also included pre-clinical cognitive impairment.

PMID- 18049009
TI  - [Comparison of ability-based and performance-based IADL evaluation of community
      dwelling elderly using the Kihon Checklist and TMIG Index of Competence].
AB  - AIM: Elderly populations are evaluated on their ability to perform instrumental
      activities of daily living (IADL) using one of three subscales in the Tokyo
      Metropolitan Institute of Gerontology (TMIG) Index of Competence, while the Kihon
      Checklist-a tool developed to screen for frailty-is designed to measure actual
      task performance. This study examined the significance of performance-based
      evaluations. METHODS: Using five items from the TMIG Index of Competence
      assessing ability, and three items included in the Kihon Checklist assessing
      performance, 124 community-dwelling elderly persons were evaluated in five daily
      task areas: using public transportation; shopping for daily necessities; handling
      bank accounts; paying bills; and preparing meals. Physical, psychological and
      social functioning were also assessed during the evaluations. RESULTS: The study
      revealed discrepancies between participants' abilities and their performance
      levels of the same daily tasks. Of the respondents, 12.5% men and 13.4% women
      reported that "they could perform all three tasks on the Kihon Checklist, but in
      actuality did not perform at least one of them". This "borderline-performance
      group" indicated a lower functioning level than those who answered "they
      performed all tasks" in all three physical, psychological and social domains.
      However, this group indicated a higher functioning level than those reporting
      that it was "impossible to perform at least one task" in all three domains.
      CONCLUSION: Study findings suggested that borderline-performance was related to
      the early stage of functional decline. The performance-based IADL evaluation is
      an effective screening tool for preventive declines in daily task performance.

PMID- 18049010
TI  - [Effect of size of tablets on easiness of swallowing and handling among the frail
      elderly].
AB  - AIM: The purpose of the present study was to examine the effect of the size of
      tablets on the status of swallowing and handling during taking medicine among
      frail elderly persons. METHODS: The subjects of the present study were 73 frail
      elderly persons. After they conducted simulation taking medicine, they determined
      the desirable size of tablets using subjective evaluation. Their behavior and the
      time required for the simulation were examined. We also evaluated their
      activities of daily living using the ADL20, and swallowing ability using the
      repetitive saliva swallowing test (RSST). RESULTS: There was a significant
      difference in behavior during taking medicine between the frail elderly with low
      swallowing ability and other subjects with normal swallowing ability, that is,
      the elderly persons with low swallowing ability tend to swallow three tablets
      after several trials (p<0.05). Also, the required time for simulation taking
      medicine was related significantly to the size of tablets (p<0.01). CONCLUSION:
      The most desirable size based upon easiness of swallowing and handling is 7-8mm.
      These results suggest that medicine taking behavior was influenced greatly by the
      decline of swallowing ability and ADL, and the prescriptions for the frail
      elderly are needed to meet their swallowing ability.

PMID- 18049011
TI  - [Correlation between vitamin D and functional capacity, physical function among
      Japanese frail elderly living in the community].
AB  - AIM: To examine the distribution of 25-hydroxyvitamin D(3) [25(OH)D] levels among
      the Japanese frail elderly, and to explore any association in these subjects
      between 25 (OH)D levels and functional capacity or physical performance. METHODS:
      A cross-sectional survey was conducted in a town (latitude 36 degrees north) in
      June 2005 to September 2006. The 76 participants were community-dwelling elderly
      aged 65 years and over who attended a class for nursing care prevention. An
      interview was conducted based on a questionnaire. The serum levels of 25(OH)D,
      intact parathyroid hormone (iPTH) and calcium were measured. The following
      physical tests were performed: timed up and go (TUG), a 5-meter walk, functional
      reach, trunk flexion, and grip strength. Functional capacity and physical
      performance were compared between the subjects with 25(OH)D>or=50 nmol/L and
      those with 25(OH)D<50 nmol/L. RESULTS: About 52.6% experienced falls, 75.0%
      experienced stumbling or body sway more than once during the past year, and 20.0%
      were housebound. The mean 25(OH)D level (+/-SD) was 60.4+/-13.6 nmol/L (range:
      27.5-87.5). The ratio of the 25(OH)D level below 50.0 nmol/L was significantly
      higher in the group of subjects who had lower mobility or body imbalance or were
      housebound. The risk factor for stumbling or body sway was 25(OH)D<50 nmol/L (OR:
      4.41, 95%CI: 1.31-14.86). CONCLUSION: The prevalence of 25(OH)D<50 nmol/L was 21%
      among Japanese frail elderly, and 25(OH)D deficiency is associated with lower
      mobility or body imbalance. It is suggested that the level of 25(OH)D should be
      needed over 50 nmol/L for nursing care prevention in the frail elderly and that
      measurements of 25(OH)D for the frail elderly are needed.

PMID- 18049012
TI  - [Studies on factors related to delayed discharge of elderly patients from
      university hospitals].
AB  - PURPOSE: To elucidate factors associated with delayed discharge of elderly
      patients from university hospitals in Japan. METHODS: Questionnaires were sent to
      all 125 Japanese university hospitals during the period from January, 18 through
      March, 25, 2004. Thirty-four possible reasons for the delayed discharge were
      analyzed. RESULTS: Family issues were the most common reason for delayed
      discharge nationwide. Medical treatment was a factor in delayed discharge in
      metropolitan areas where university hospitals were under pressure to reduce the
      mean hospital stay. The lack of chronic beds was identified as a factor
      associated with delayed discharge. However, the low quality of care at institutes
      in rural areas may possibly cause delayed discharge, despite adequate number of
      chronic beds. CONCLUSIONS: Despite the Japanese government encouraging the care
      of elderly people at home, the present study shows that the leading cause of
      delayed discharge is that families cannot accept elderly patients directly from
      university hospitals. Even if the number of chronic beds were to increase, the
      quality of care provided would not be adequate to allow a smooth transition of
      elderly patients from university hospitals to such chronic beds in some areas.

PMID- 18049013
TI  - [A 94-year-old woman with nontuberculous mycobacterium who developed small
      intestinal intussusception associated with a percutaneous endoscopic jejunostomy
      tube].
AB  - We report a 94-year-old woman, who underwent percutaneous endoscopic Jejunostomy
      (PEJ) tube feeding for enteral nutrition, developed the intussusception of the
      small intestine. She suffered from nontuberculous mycobacterium (NTM), and her
      lung inflammation deteriorated due to aspiration pneumonia and malnutrition.
      Because of old age, dysphagia, esophageal hiatus hernia, gastro-esophageal reflux
      and her bedridden condition due to severe osteoporosis, oral nutritional
      supplementation is nearly impossible. To reduce the aspiration risk, we chose PEJ
      instead of percutaneous endoscopic gastrostomy (PEG) as the route of tube
      feeding. Six months after the placement of a PEJ tube, aspiration pneumonia was
      diagnosed and she was readmitted to our hospital. During hospitalization, she had
      sudden diarrhea, vomiting, and lower abdominal pain. Abdominal CT scan and
      radiographs using contrast medium showed small intestinal intussusception related
      to the PEJ tube. We observed the clinical course without performing surgery,
      pulling it back towards the stomach and placing an ileus tube, because the small
      intestine was not completely obstructed. Two months later, although she suffered
      from aspiration pneumonia once more, she remained in a stable condition without
      further intervention so that she could move to aother hospital. Recently PEJ has
      been expected to prevent aspiration pneumonia, but we believe that it can be a
      risk factor for intussusception. Although the PEJ can be a good parenteral
      nutrition route for frail elderly with dysphagia, we need to consider possible
      complications including intussusception.

PMID- 18049014
TI  - [A criticism on the editorial policy].

PMID- 18049016
TI  - Improvement of arterial stiffness by aerobic exercise in elderly subjects.

PMID- 18049017
TI  - The morning-evening difference in self-measured blood pressure: a potential
      predictor of cardiovascular disease.

PMID- 18049018
TI  - Report of the Working Group for Dietary Salt Reduction of the Japanese Society of
      Hypertension: (1) Rationale for salt restriction and salt-restriction target
      level for the management of hypertension.
AB  - Salt excess is well known to be involved in the pathophysiology of hypertension,
      and thus restriction of salt intake is widely recommended for management of the
      disease. Excessive salt intake induces blood pressure (BP)-dependent as well as 
      independent progression of cardiovascular disease. Although the human body is
      considered to be adapted to very low salt intake (0.5-3 g/day), restriction to
      such a low level of salt intake is extremely difficult to accomplish in developed
      countries. Significant BP reduction has been reported in large-scale clinical
      studies in which salt intake was decreased to less than 6 g/day, and the results
      of a meta-analysis have shown that systolic BP was reduced about 1 mmHg with
      every decrease in salt intake of 1 g/day in hypertensive subjects. Current
      guidelines for the treatment of hypertension, including Japanese guidelines,
      recommend dietary salt reduction to 6 g/day or less in hypertensive patients.
      However, it appears to be fairly difficult to attain this target of salt intake,
      especially in Japan. There is thus a need for feasible and effective measures to
      attain this salt restriction target.

PMID- 18049019
TI  - Report of the Working Group for Dietary Salt Reduction of the Japanese Society of
      Hypertension: (2) Assessment of salt intake in the management of hypertension.
AB  - Restriction of dietary salt is widely recommended in the management of
      hypertension, but assessment of individual salt intake has drawn little
      attention. The understanding of salt intake is important as a guide for
      optimizing salt-restriction strategies. However, precise evaluation of salt
      intake is difficult. More reliable methods are more difficult to perform, whereas
      easier methods are less reliable. Thus, the method to assess salt intake should
      be determined as the situation demands. The Working Group for Dietary Salt
      Reduction of the Japanese Society of Hypertension recommends the assessment of
      individual salt intake using one of the following methods in the management of
      hypertension. 1) The measurement of the sodium (Na) excretion from 24-h urine
      sampling or nutritionist's analysis of the dietary contents, which are reliable
      but difficult to perform, are suitable for facilities specializing in the
      treatment of hypertension. 2) Estimation of the Na excretion from the
      Na/creatinine (Cr) ratio in spot urine is less reliable but practical and is
      suitable for general medical facilities. 3) Estimation using an electronic salt
      sensor equipped with a calculation formula is also less reliable but is simple
      enough that patients can use it themselves. The patients are considered to be
      compliant with the salt-restriction regimen if salt intake measured by whichever
      method is less than 6 g (100 mmol)/day.

PMID- 18049020
TI  - Effect of acute and long-term aerobic exercise on arterial stiffness in the
      elderly.
AB  - Arterial stiffness is an important factor for cardiovascular performance and a
      predictor of cardiovascular risk. We evaluated the effects of both acute and long
      term aerobic exercise on arterial stiffness in community-dwelling healthy elderly
      subjects. In addition, we evaluated the relationship between the effects of long
      term exercise and those of acute exercise. The study subjects were participants
      in the Shimanami Health Promoting Program study (J-SHIPP), which was designed to
      investigate factors relating to cardiovascular disease, dementia, and death (67+/
      6 years). They performed mild-to-moderate aerobic exercise lasting for 30 min
      twice a week for 6 months. Arterial stiffness was assessed before and after the
      first 30-min acute exercise (n=99) and long-term 6-month aerobic training (n=40).
      The radial arterial augmentation index (AI) obtained from the radial pulse
      waveform by the tonometry method was used as a parameter of arterial stiffness.
      Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were
      significantly decreased after 30-min of aerobic exercise, however no significant
      change in AI was observed. On the other hand, there were significant decreases in
      AI (from 87 to 84%, p<0.01), SBP (from 136 to 129 mmHg, p<0.01), and DBP (from 75
      to 70 mmHg, p<0.01) after the 6-month exercise period. Long-term exercise-induced
      changes in AI were significantly and inversely correlated with the pre-exercise
      AI (r=-0.40, p<0.01). In addition, AI changes after the 6-month exercise period
      were significantly related to those observed after first 30-min exercise (r=0.48,
      p<0.01). These findings indicate that apparently healthy and sedentary elderly
      subjects with higher AI may benefit from mild-to-moderate aerobic exercise to
      improve arterial stiffness.

PMID- 18049021
TI  - Morning rise of blood pressure assessed by home blood pressure monitoring is
      associated with left ventricular hypertrophy in hypertensive patients receiving
      long-term antihypertensive medication.
AB  - To assess the influence of morning rise of systolic blood pressure (SBP) as
      assessed by home blood pressure monitoring on the left ventricular mass index
      (LVMI) in relation to the blood pressure control status, we evaluated M-mode
      cardiac echocardiography in 626 hypertensive subjects (412 men and 214 women;
      mean age, 61.3+/-10.1 years) who were receiving antihypertensive medication. The
      subjects were requested to measure their blood pressure at home in the morning
      and evening over a 3-month period. They were distributed into the following four
      groups by the average (ME Ave) and the difference (ME Dif) of the morning and
      evening SBP. The well-controlled hypertensives with a morning rise of SBP (ME
      Ave<135 mmHg and ME Dif>or=10 mmHg; n=45; 7.2%) had a greater LVMI (122.9+/-22.7
      vs. 92.7+/-15.6 g/m2, p<0.001) than the well-controlled hypertensives without a
      morning rise of SBP (ME Ave<135 mmHg and ME Dif<10 mmHg; n=367; 58.6%). The
      uncontrolled hypertensives with a morning rise of SBP (ME Ave>or=135 mmHg and ME
      Dif>or=10 mmHg; n=91; 14.5%) also had a greater LVMI (136.8+/-21.9 vs. 100.2+/
      17.5 g/m2, p<0.001) than the uncontrolled hypertensives without a morning rise of
      SBP (ME Ave>or=135 mmHg and ME Dif<10 mmHg; n=123; 19.6%). A stepwise
      multivariate regression analysis revealed that the ME Dif was the most important
      factor related to the LVMI (r2=35.1% for all subjects, p<0001; r2=39.7% for men,
      p<0.001; and r2=18.7% for women, p<0.001). These results suggest that morning
      rise of blood pressure is an important factor influencing the development of left
      ventricular hypertrophy in hypertensive patients on antihypertensive medication.

PMID- 18049022
TI  - Long-term oral administration of dipyridamole improves both cardiac and physical
      status in patients with mild to moderate chronic heart failure: a prospective
      open-randomized study.
AB  - Adenosine is known as an endogenous cardioprotectant. We previously reported that
      plasma adenosine levels increase in patients with chronic heart failure (CHF),
      and that a treatment that further elevates plasma adenosine levels may improve
      the pathophysiology of CHF. Therefore, we performed a prospective, open
      randomized clinical trial to determine whether or not exposure to dipyridamole
      for 1 year improves CHF pathophysiology compared with conventional treatments.
      The study enrolled 28 patients (mean+/-SEM: 66+/-4 years of age) attending
      specialized CHF outpatient clinics with New York Heart Association (NYHA) class
      II or III, no major complications, and stable CHF status during the most recent 6
      months under fixed medications. They were randomized into three groups with or
      without dipyridamole (Control: n=9; 75 mg/day: n=9; 300 mg/day: n=10) in addition
      to their original medications and were followed up for 1 year. The other drugs
      were not altered. Among the enrolled patients, 100%, 4%, 100%, and 79% received
      angiotensin-converting enzyme inhibitors, aldosterone analogue, loop diuretics,
      and beta-adrenoceptor blocker, respectively. Fifteen patients suffered from
      dilated cardiomyopathy, and 7/3/3 patients suffered from
      ischemic/valvular/hypertensive heart diseases, respectively. Mean blood pressure
      was comparable among the groups. While the baseline conditions were comparable,
      we found that echocardiographic ejection fraction (p<0.01 vs. baseline, p<0.01
      vs. Control), left ventricular systolic diameter (p<0.05, p<0.05), Specific
      Activity Scale (SAS) score (p<0.05, p<0.01), maximal oxygen consumption (p<0.05,
      p<0.05) and plasma B-type natriuretic peptide level (p<0.01, p<0.01) were
      significantly improved in patients with dipyridamole after 1 year, generally in a
      dose-dependent manner. Therefore, we suggest that an additional administration of
      dipyridamole further improves CHF pathophysiology.

PMID- 18049023
TI  - Awareness and treatment of hypertension and hypercholesterolemia in Japanese
      workers: the High-risk and Population Strategy for Occupational Health Promotion
      (HIPOP-OHP) study.
AB  - The objective of this study was to clarify the awareness and treatment status of
      hypertension in Japanese workers, comparing with those of hypercholesterolemia.
      The subjects were 6,186 workers (age 19 to 69 years), who worked at 12 workplaces
      in Japan and who continuously participated in the High-risk and Population
      Strategy for Occupational Health Promotion (HIPOP-OHP) study at the baseline
      (1999 or 2000) and the subsequent year (2000 or 2001). No intervention was
      performed during the study period. Blood pressure and total cholesterol level
      were measured at baseline. Awareness and treatment status were examined by a self
      administered questionnaire in the following year. Untreated subjects were defined
      as those were not aware of hypertension (or hypercholesterolemia) or those not
      taking medication and not undergoing lifestyle modification. The percentages of
      subjects with hypertension defined as aware were 65.7% in men and 72.7% in women,
      respectively. The percentages of subjects with hypercholesterolemia defined as
      aware were 55.7% in men and 58.6% in women, respectively. In subjects 40 years
      and older, the awareness rate for hypertension was significantly higher than the
      awareness rate for hypercholesterolemia (75.0% vs. 59.2%, p<0.001). The
      percentage of untreated subjects with hypertension was significantly lower than
      the percentage of untreated subjects with hypercholesterolemia (41.0% vs. 57.1%,
      p<0.001). Although Japanese workers >/=40 years old have a higher awareness of
      and are more often treated for hypertension than for hypercholesterolemia, there
      are still many unaware and untreated individuals with either disease in all age
      groups. It is important to increase the awareness of risk factors in individuals
      with positive findings for these conditions.

PMID- 18049024
TI  - Renoprotective effect of the addition of losartan to ongoing treatment with an
      angiotensin converting enzyme inhibitor in type-2 diabetic patients with
      nephropathy.
AB  - Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin II receptor
      blockers (ARBs) are frequently used for the treatment for glomerulonephritis and
      diabetic nephropathy because of their albuminuria- or proteinuria-reducing
      effects. To many patients who are nonresponsive to monotherapy with these agents,
      combination therapy appears to be a good treatment option. In the present study,
      we examined the effects of the addition of an ARB (losartan) followed by
      titration upon addition and at 3 and 6 months (n=14) and the addition of an ACE-I
      followed by titration upon addition and at 3 and 6 months (n=20) to the drug
      regimen treatment protocol in type 2 diabetic patients with nephropathy for whom
      more than 3-month administration of an ACE-I or the combination of an ACE-I plus
      a conventional antihypertensive was ineffective to achieve a blood pressure (BP)
      of 130/80 mmHg and to reduce urinary albumin to <30 mg/day. During the 12-month
      treatment, addition of losartan or addition of an ACE-I to the treatment protocol
      reduced systolic blood pressure (SBP) by 10% and 12%, diastolic blood pressure
      (DBP) by 7% and 4%, and urinary albumin excretion by 38% and 20% of the baseline
      value, respectively. However, the effects on both BP and urinary albumin were not
      significantly different between the two therapies. In conclusion, addition of
      losartan or an ACE-I to an ongoing treatment with an ACE-I, or addition of an ACE
      I to ongoing treatment with a conventional antihypertensive were equally
      effective at reducing the urinary albumin excretion and BP, and provided renal
      protection in patients with type-2 diabetic nephropathy.

PMID- 18049025
TI  - Metabolic syndrome and risk of developing chronic kidney disease in Japanese
      adults.
AB  - Metabolic syndrome is a risk factor for the development of cardiovascular
      disease. Few prospective studies, however, have examined metabolic syndrome as a
      risk factor for chronic kidney disease (CKD) in an Asian population. We studied
      the occurrence of CKD in 6,371 subjects without CKD or diabetes mellitus at
      baseline 1997 through 2002 in Okinawa, Japan. CKD was defined as dipstick
      positive proteinuria (>or=1+) or a low estimated glomerular filtration rate (<60
      mL/min/1.73 m2). Metabolic syndrome was defined according to the modified
      criteria of the Adult Treatment Panel III in which body mass index (>or=25 kg/m2)
      was substituted for the waist circumference measurement. Logistic analysis was
      used to analyze the effect of metabolic syndrome on the development of CKD.
      During the 5-year follow-up, 369 (5.7%) participants developed CKD. After
      adjusting for age, sex, current cigarette smoking and alcohol drinking habits at
      baseline, the relative risk of developing CKD was 1.86 (95% confidence interval:
      1.43-2.41, p<0.0001) in subjects with metabolic syndrome. Compared with those
      without metabolic syndrome risk components, the adjusted relative risk (95%
      confidence interval) was 1.49 (1.10-2.01), 1.89 (1.38-2.59), and 2.65 (1.19-3.68)
      in those with 1, 2, or >or=3 metabolic syndrome risk components, respectively.
      Metabolic syndrome is a significant risk factor for the development of CKD in the
      Japanese population. Detection and treatment of metabolic syndrome should be
      stressed as a strategy to prevent CKD.

PMID- 18049026
TI  - Lower birth weight is associated with higher resting heart rate during boyhood.
AB  - There is substantial evidence that low birth weight is associated with the
      development of cardiovascular disease in adult life. Moreover, resting heart rate
      is a prognostic factor of cardiovascular morbidity and mortality. However, there
      are scarce data regarding the association between birth weight and resting heart
      rate in later life. Therefore, we investigated the association of anthropometric
      data at birth and hemodynamic indices including resting heart rate in Japanese
      boys. The data of 1,107 male students of a junior high school in Tokyo, Japan,
      who underwent a medical check-up in the year of admission to the school (12 or 13
      years old) were used. Information on anthropometric data at birth based on "The
      Maternal and Child Health Handbook" was obtained from 573 students. From a
      standard 12-channel resting electrocardiogram, 8 cardiac cycles were used to
      estimate heart rate. Resting heart rate correlated positively with body mass
      index at the same age (r=0.100, p=0.017) and correlated negatively with birth
      weight (r=-0.102, p=0.015), height at birth (r=-0.125, p=0.003), and head
      circumference at birth (r=-0.095, p=0.025). The negative correlation of
      anthropometric data at birth with heart rate at the age of 12 or 13 was
      independent of body mass index at the same age. The mean value of resting heart
      rate at the age of 12 or 13 adjusted for body mass index at the same age was
      significantly higher in the lower tertile of birth weight than in the higher
      tertile of birth weight (81.7 vs. 78.5 beats/min, p=0.028). In conclusion, lower
      birth weight is associated with higher resting heart rate during boyhood,
      suggesting that elevated heart rate may be one mechanism linking small size at
      birth with the development of cardiovascular disease in future life.

PMID- 18049027
TI  - Prevalence, awareness, treatment, and control of hypertension in rural adults
      from Liaoning Province, northeast China.
AB  - Liaoning Province is located in northeast China, which has distinct weather
      conditions, geographic characteristics and lifestyles compared with other regions
      of the country; the lifestyle differences are especially pronounced in the rural
      parts of this region, where there is a dearth of financial and other resources.
      However, information on the prevalence, awareness, treatment, and control of
      hypertension in these impoverished areas is very scarce. We therefore performed
      multistage cluster random sampling of a group of 29,970 adult residents (>or=5
      years of residency; >or=35 years of age) of the rural portions of Liaoning
      Province from 2005 to 2006. The sampling included a survey on blood pressure and
      associated risk factors. The overall prevalence of hypertension in the community
      was 36.2%, and 73.0% of hypertensives were unaware of their condition. Among the
      total group of hypertensives, only 19.8% were taking prescribed medication to
      lower their BP, and 0.9% had controlled hypertension. Of all subjects, 46.4% did
      not think that high blood pressure would endanger their lives. As to the reasons
      given by hypertensives who were aware of their hypertension for not taking
      antihypertensive medication, 47.4% reported that they lacked knowledge about the
      mortality of hypertension. The average salt intake in hypertensives was 16.6+/
      9.9 g/day, and the percentages of smoking (44.3%), drinking (31.7%) and salt
      intake>6 g/day (86.8%) in hypertensives were high. Logistic regression analysis
      indicated that the relative risks (95% confidence interval [CI]) of overweight,
      obesity, smoking, drinking, increased salt intake and family history of
      hypertension for hypertension were 1.95 (range, 1.82-2.08), 2.92 (2.40-3.55),
      1.19 (1.12-1.27), 1.16 (1.08-1.25), 1.26 (1.20-1.33) and 2.85 (2.66-3.05),
      respectively. A higher education level was found to be a protective factor. In
      conclusion, the prevalence of hypertension in adults living in the rural parts of
      Liaoning Province was high, and the rates of awareness, treatment, and control
      were unacceptably low, which may have been due to unique geographical
      characteristics, unwholesome lifestyles, greater sodium intake, lower education
      levels, and genetic risk factors.

PMID- 18049028
TI  - Impact of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 system
      on large arterial stiffness in patients with essential hypertension.
AB  - The extracellular matrix is vital for maintaining tissue integrity, and the
      matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs)
      system is involved in the regulation of extracellular matrix metabolism.
      Extracellular matrix turnover plays an important role in the change of large
      arterial mechanical properties in hypertension. However, the association of the
      metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) system
      and arterial stiffness is not straightforward and existing data are rather
      limited. Our objective is to explore the impact of the MMP-9/TIMP-1 system on
      large arterial stiffness in patients with essential hypertension. An automatic
      pulse wave velocity (PWV) measuring system was used to examine carotid-femoral
      PWV (CFPWV) and carotid-radial PWV (CRPWV) as the parameters reflecting central
      elastic large arterial and peripheral muscular medium-sized arterial elasticity,
      respectively; and serum MMP-9 and TIMP-1 levels, along with a number of other
      established biomarkers, were measured by enzyme-linked immunosorbent assay
      (ELISA) in 202 essential hypertensive patients and 54 age and gender-matched
      control subjects. Compared with the control subjects, hypertensive patients
      exhibited higher levels of MMP-9 (p=0.001) and TIMP-1 (p=0.002). Spearman's
      correlation analysis showed that serum levels of MMP-9 (p=0.014) and TIMP-1
      (p=0.005) were significantly and positively correlated with CFPWV in hypertensive
      patients. A stepwise multiple regressive analysis demonstrated that age, systolic
      blood pressure, heart rate and TIMP-1 were independent predictors of CFPWV in
      patients with essential hypertension (adjusted r2=0.458). In conclusion, our
      results imply that the MMP-9/TIMP-1 system may play an important role in the
      determination of arterial function, and these findings may have implications for
      the involvement of MMP-9/TIMP-1 system in the pathophysiology of cardiovascular
      disease.

PMID- 18049029
TI  - Influence of different measurement time points on brachial-ankle pulse wave
      velocity and ankle-brachial index in hemodialysis patients.
AB  - In order to ensure that they are reliable markers of atherosclerosis and suitable
      for repetitive follow-up of disease progression and management responses in
      hemodialysis (HD) patients, brachial-ankle pulse wave velocity (baPWV) and ankle
      brachial index (ABI) should be tested to see whether they change with different
      measurement time points. The aim of this study was to assess whether baPWV and
      ABI vary according to whether they are measured before HD, after HD, or on the
      next dialysis-free day. Eighty-nine patients undergoing regular HD were enrolled.
      The baPWV and ABI were measured 10-30 min before and after HD, and if patients
      agreed, on the next dialysis-free day. The third measurement of baPWV and ABI,
      performed 22+/-2 h after HD, was taken in 72 patients (81%). The body weight
      reduction after HD was 2.5+/-0.9 kg (p<0.001). The brachial and ankle systolic
      and diastolic blood pressures before HD were significantly higher than those
      after HD and on the next dialysis-free day (p<or=0.038). Right and left baPWV
      increased significantly after HD (p<or=0.006), but returned to the pre-dialysis
      level on the next dialysis-free day. However, the right and left ABI remained
      constant before and after HD, or on the next dialysis-free day (p>or=0.498). In
      conclusion, despite the significant decrease in body weight and blood pressures,
      baPWV increased significantly after HD. In addition, baPWV, but not ABI, may vary
      at different measurement time points. Therefore, baPWV, but not ABI, should be
      assessed in a timely manner in HD patients.

PMID- 18049030
TI  - Inhibition of balloon injury-induced neointimal formation by olmesartan and
      pravastatin in rats with insulin resistance.
AB  - The combined effect of an angiotensin II type 1 receptor blocker and a 3-hydroxy
      3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor on vascular lesion
      formation in the insulin-resistant state has not been examined. We tested whether
      or not combined treatment is superior to single-drug treatment for inhibiting
      vascular lesion formation in insulin-resistant rats. The rats were maintained on
      a fructose-rich diet for 4 weeks and then treated with olmesartan (1 mg/kg/day)
      and/or pravastatin (10 mg/kg/day) for 3 weeks. After 1 week of drug treatment,
      balloon injury of the carotid arteries was performed. Two weeks later, the
      injured arteries were harvested for morphometry and immunostaining. Olmesartan
      and pravastatin each modestly attenuated neointimal formation without significant
      changes in blood pressure or serum lipid levels. The combination of olmesartan
      and pravastatin significantly suppressed the neointimal formation compared with
      either monotherapy. The number of terminal deoxynucleotidyl transferase-mediated
      dUTP nick end-labeling (TUNEL)-positive cells was increased by olmesartan but not
      by pravastatin. Olmesartan and pravastatin each decreased the number of Ki-67
      positive cells, which indicates cell proliferation, to the same extent. The
      combined treatment increased the number of TUNEL-positive cells but did not
      affect the number of Ki-67-positive cells. The combined treatment decreased the
      insulin level and increased the number of circulating endothelial progenitor
      cells. These results suggest that the combination of olmesartan and pravastatin
      is beneficial for the treatment of vascular diseases in the insulin-resistant
      state independently of blood pressure or cholesterol levels.

PMID- 18049031
TI  - Aldosterone-and-salt-induced cardiac fibrosis is independent from angiotensin II
      type 1a receptor signaling in mice.
AB  - Aldosterone infusion with high salt treatment induces cardiac fibrosis in rats.
      Aldosterone enhanced angiotensin II (Ang II) has been shown to induce
      proliferation and increase the expression of Ang II receptor mRNA and Ang II
      binding in vitro. To investigate the role of Ang II type 1a receptor (AT1aR) in
      aldosterone-and-salt (Ald-NaCl)-induced cardiac fibrosis, we subcutaneously
      infused aldosterone (0.15 microg/h) and 1% NaCl (Ald-NaCl) into AT1aR knockout
      mice (AT1aR-KO) or wild type mice (Wt). To examine the role of NaCl on cardiac
      fibrosis, we gave some of the aldosterone-treated AT1aR-KO tap water (Ald-H2O).
      Ald-NaCl treatment increased systolic blood pressure and induced cardiac
      hypertrophy in both strains, whereas there were no such changes in the mice
      without aldosterone. Severe cardiac fibrosis was seen in Ald-NaCl-treated AT1aR
      KO and not in Ald-NaCl-treated Wt. In contrast, Ald-NaCl-treated Wt with co
      administration of an active metabolite of olmesartan, the AT1aR antagonist (10
      mg/kg/day) did not show cardiac fibrosis. Na+/H+ exchanger, and Na+-K+ ATPase
      alpha2 subunit mRNA were decreased in AT1aR-KO. Na+/Ca2) exchanger mRNA was lower
      in AT1aR-KO than Wt and was decreased by Ald-NaCl in both strains.
      Phosphorylation of epidermal growth factor receptor and extracellular signal
      regulated kinase was increased by Ald-NaCl treatment in AT1aR-KO. Connective
      tissue growth factor (CTGF) and osteopontin mRNA were increased and accumulation
      of CTGF proteins was seen in the hearts of Ald-NaCl-treated AT1aR-KO. Ald-H2O
      treated AT1aR-KO did not show any cardiac fibrosis. These results suggest that
      Ald-NaCl-induced cardiac fibrosis required both aldosterone and salt. Because
      cardiac fibrosis was exaggerated in Ald-NaCl-treated AT1aR-KO but was not seen in
      Wt treated with Ald-NaCl and olmesartan, AT1aR may not play a primary role in
      progression of cardiac fibrosis by Ald-NaCl, and gene disruption of AT1aR may
      have some implications in this model.

PMID- 18049032
TI  - Albuminuria, expression of nicotinamide adenine dinucleotide phosphate oxidase
      and monocyte chemoattractant protein-1 in the renal tubules of hypertensive Dahl
      salt-sensitive rats.
AB  - In chronic renal diseases, experimental and human data suggest that excess
      albumin filtered through the glomerular capillary barrier is over-reabsorbed by
      proximal tubular cells, thereby activating these cells and upregulating the
      expression of chemokines. On the other hand, a high-salt diet has been shown to
      induce proteinuria in hypertensive Dahl salt-sensitive (DSS) rats, accompanied
      with the expression of reduced nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase in the kidney. In the current study, we therefore examined
      albuminuria and the expressions of NADPH oxidase and monocyte chemoattractant
      protein-1 (MCP-1) in the renal tubular cells in hypertensive DSS rats, as well as
      the effects of the antioxidant N-acetylcysteine (NAC) on each of these
      parameters. DSS rats were fed a normal-salt diet (0.24% NaCl), a high-salt diet
      (8% NaCl), or a high-salt diet plus NAC supplementation (15 mg/mL drinking water)
      for 4 weeks. The high-salt diet provoked an increase in glomerular injuries
      accompanied with albuminuria and in urinary H2O2 and MCP-1 excretion.
      Immunohistochemical analysis showed the prominent expression of MCP-1 in the
      dilated tubular cells, where the NADPH oxidase subunit p47phox was also
      expressed. The current results suggest that albuminuria caused expression of
      NADPH oxidase and MCP-1 in the dilated renal tubules, resulting in interstitial
      inflammation and migration of mononuclear cells in DSS rats, because blockade of
      albuminuria by NAC counteracted the p47phox and MCP-1 expression.

PMID- 18049033
TI  - Dilation of renal artery stenosis after administration of losartan.
AB  - Transluminal angioplasty with a balloon catheter is effective to dilate renal
      artery stenosis (RAS) caused by fibromuscular dysplasia (FMD), but lesions
      resistant to the angioplasty exist. In this report, we describe the case of a
      young woman with RAS of FMD that was difficult to dilate even by cutting-balloon
      angioplasty. To facilitate the formation of a smooth intimal covering at the site
      of angioplasty, we administered losartan, an angiotensin receptor blocker, for 4
      months after the angioplasty. Although re-stenosis was detected at 5 months after
      the angioplasty, the normotensive state continued without antihypertensives and
      the re-stenosis gradually dilated afterwards. The present case suggests the
      possibility of remodeling the renal artery during the normotensive state by
      administering losartan after the angioplasty.

PMID- 18049034
TI  - Gene expression profiles in mouse liver cells after exposure to different types
      of radiation.
AB  - The liver is one of the target organs of radiation-induced cancers by internal
      exposures. In order to elucidate radiation-induced liver cancers including
      Thorotrast, we present a new approach to investigate in vivo effects of internal
      exposure to alpha-particles. Adopting boron neutron capture, we separately
      irradiated Kupffer cells and endothelial cells in mouse liver in vivo and
      analyzed the changes in gene transcriptions by an oligonucleotide microarray.
      Differential expression was defined as more than 3-fold for up-regulation and
      less than 1/3 for under-regulation, compared with non-irradiated controls. Of
      6,050 genes examined, 68 showed differential expression compared with non
      irradiated mice. Real-time polymerase chain reaction validated the results of the
      microarray analysis. Exposure to alpha-particles and gamma-rays produced
      different patterns of altered gene expression. Gene expression profiles revealed
      that the liver was in an inflammatory state characterized by up-regulation of
      positive acute phase protein genes, irrespective of the target cells exposed to
      radiation. In comparison with chemical and biological hepatotoxicants, inductions
      of Metallothionein 1 and Hemopexin, and suppressions of cytochrome P450s are
      characteristic of radiation exposure. Anti-inflammatory treatment could be
      helpful for the prevention and protection of radiation-induced hepatic injury.

PMID- 18049035
TI  - Abdominal radiation initiates apoptotic mechanism in rat femur bone marrow cells
      in vivo that is reversed by IGF-1 administration.
AB  - PURPOSE: Radiation induces apoptosis as a result of damage to cellular DNA and
      RNA. The aim of our work was to study the effect of radiation on rat bone marrow
      cells (as a neighboring tissue) in the context of a model of experimental
      radiation enteritis in rats. The effect of systematic administration in
      irradiated animals of r-IGF-1 and GH was also studied. MATERIALS AND METHODS:
      Wistar type, normal rats, were divided in 4 groups. One control group and the
      other 3 groups were irradiated in the abdomen. The measured scattered irradiation
      in the femur ranged from 16.5 to 47.3 cGy. In 2 groups of irradiated animals,
      rIGF-1 (0.1 microg/g of body weight twice/d) and rGH (0.25 microg/g of body
      weight /d) were administered. Bone marrow cells were harvested from both femurs.
      DNA and RNA were analyzed in specific gels. The m-RNA was hybridized for c-fos
      proto-oncogene expression. RESULTS: The calculated low dose of radiation that
      affected the femurs of the animals induced reduction in bone marrow cell numbers
      and endonuclease activation manifested by subsequent fragmentation of DNA and
      RNA. This phenomenon was reversed by rGH and rIGF-1 administration. The c-fos
      proto-oncogene expression was upregulated by irradiation. CONCLUSION: These
      observations indicate that scattered low dose radiation is capable of initiating
      apoptosis in rat bone marrow cells and rGH and rIGF-1 administration reverse this
      process.

PMID- 18049036
TI  - Off the assembly line.

PMID- 18049038
TI  - Who will teach tomorrow's nurses?

PMID- 18049037
TI  - Have nurses turned a blind eye?

PMID- 18049039
TI  - Unnecessary C-sections.

PMID- 18049047
TI  - U.S. hospitals need staffing makeover.

PMID- 18049049
TI  - Keeping new RNs in their jobs.

PMID- 18049048
TI  - Cost-effective, culturally specific diabetes care.

PMID- 18049051
TI  - 'Every patient deserves an RN'--kids, too.

PMID- 18049052
TI  - Little women.

PMID- 18049058
TI  - 'Not tonight, dear': the elusive female libido.

PMID- 18049059
TI  - Nurses' decisions about opioid dose.

PMID- 18049060
TI  - How the new oral antineoplastics affect nursing practice: capecitabine serves to
      illustrate.
AB  - The increasing use of oral anticancer drugs has profound implications for cancer
      treatment and nursing practice, shifting care from hospitals to outpatient
      settings and from oncology specialists to patients, families, and caregivers.
      Nurses will focus less on drug administration and more on educating patients,
      monitoring for adverse effects, and performing follow-up care. This article
      discusses how these new drugs are affecting nursing practice, focusing on one
      novel oral agent-capecitabine (Xeloda), approved for treating metastatic
      colorectal and breast cancer and as adjuvant therapy for stage 3 (Dukes's C)
      colon cancer-to illustrate.

PMID- 18049062
TI  - How to try this: detecting delirium.
AB  - For patients and their loved ones, delirium can be a frightening experience. A
      fluctuating mental status is important to identify because it often signals a
      need for additional treatment. The Confusion Assessment Method (CAM) diagnostic
      algorithm enables nurses to assess for delirium by identifying the four features
      of the disorder that distinguish it from other forms of cognitive impairment. It
      can be completed in five minutes and is easily incorporated into ongoing
      assessments of hospitalized patients. (This screening tool is included in the
      series Try This: Best Practices in Nursing Care to Older Adults, from the
      Hartford Institute for Geriatric Nursing at New York University's College of
      Nursing.) For a free online video demonstrating the use of this tool, go to
      http://links.lww.com/A209.

PMID- 18049067
TI  - Nurses' roles in emergencies.

PMID- 18049065
TI  - How to try this: the mini-cog.
AB  - As the population grows and the proportion of older adults increases, the
      incidence and prevalence of dementia are expected to increase dramatically.
      Health care providers' lack of awareness of current geriatrics practice and
      persistence in holding the outdated belief that confusion is a normal part of
      aging contribute to significant under recognition of dementia in all settings.
      Early recognition and diagnosis are critical to carrying out best practices in
      the care of older patients. The Mini-Cog is a simple, effective, easily
      administered screening tool that can uncover cognitive impairment in its earliest
      stages. The tool consists of a three-item recall task and a simple clock-drawing
      task. The Mini-Cog takes only three to five minutes to administer and requires
      minimal training. For a free online video demonstrating the use of this tool, go
      to http://links.lww.com/A204.

PMID- 18049068
TI  - Health savings accounts: friend or foe?

PMID- 18049069
TI  - 'Pharm party'.

PMID- 18049070
TI  - One bike at a time.

PMID- 18049071
TI  - Ordinary things.

PMID- 18049072
TI  - Phenotypic variation in trismus-pseudocamptodactyly syndrome caused by a
      recurrent MYH8 mutation.
AB  - We report a 20-year-old man with trismus-pseudocamptodactyly (TPS) syndrome who
      was found to have the same MYH8 mutation, p.R674Q, described in previous families
      with TPS syndrome and in one family with a Carney complex variant, trismus and
      pseudocamptodactyly. This patient had facial asymmetry, ptosis and downslanting
      palpebral fissures and multiple joint involvement, with bilateral hip dysplasia,
      reduced elbow supination, vertical tali and talipes in addition to the classical
      findings of trismus and pseudocamptodactyly. These findings broaden the phenotype
      associated with p.R674Q mutations and support the use of MYH8 testing in patients
      with a clinical diagnosis of TPS syndrome.

PMID- 18049073
TI  - Screening for subtelomeric chromosome alteration in a consecutive series of
      newborns with congenital defects.
AB  - It is generally accepted that 2.5% of the patients with unexplained mental
      retardation and dysmorphic features have a chromosome alteration affecting the
      subtelomeric regions. The frequency of such alterations whether in the general
      population or in newborns with congenital defects, however, remains unknown.
      Here, we present an analysis of the subtelomeric regions in a consecutive series
      of 71 newborn babies with congenital defects, who displayed a normal high
      resolution G-band karyotype (550-850 bands). After excluding the alterations that
      could be considered to be polymorphisms, a total of seven subtelomeric anomalies
      were observed with a frequency of 9.86% (3.96-20.31). We conclude that
      fluorescence in-situ hybridization screening for subtelomeric alterations is
      relevant for infants with congenital defects detectable at birth, particularly in
      those newborn babies with congenital defects and a normal high resolution G-band
      karyotype.

PMID- 18049074
TI  - Expanding the phenotype of 22q11 deletion syndrome: the MURCS association.
AB  - The MURCS association [Mullerian Duct aplasia or hypoplasia (M), unilateral renal
      agenesis (UR) and cervicothoracic somite dysplasia (CS)] manifests itself as
      Mullerian Duct aplasia or hypoplasia, unilateral renal agenesis and
      cervicothoracic somite dysplasia. We report on a 22-year-old woman with
      bicornuate uterus, right renal agenesis, C2-C3 vertebral fusion (MURCS
      association) and 22q11.2 deletion. Angio-MRI revealed the aberrant origin of arch
      arteries. Hashimoto thyroiditis, micropolycystic ovaries with a dermoid cyst in
      the right ovary and mild osteoporosis were also diagnosed. Accurate revision of
      radiographs enabled us also to identify thoracolumbar and lumbosacral vertebral
      differentiation defects. Audiometry and echocardiogram were normal. Bone
      densitometry showed osteoporosis. As per our evaluation, the patient had short
      stature, obesity (BMI 30.7) and facial features suggestive of the 22q11 deletion
      syndrome. Multiplex ligation-dependent probe amplification analysis showed a de
      novo 22q11.2 deletion confirmed by array-comparative genomic hybridization
      analysis. We discuss whether this is a casual association or whether it is an
      additional syndrome owing to the well known phenotype extensive variability of
      the 22q11 deletion syndrome.

PMID- 18049075
TI  - Recombination of a maternal pericentric inversion results in 22q13 deletion
      syndrome.
AB  - We describe a 10-month-old boy with 22q13 deletion syndrome. Chromosomal analysis
      showed a partial duplication of 22p11.2-pter and a terminal deletion of 22q13.31
      qter. Maternal chromosomal analysis showed a pericentric inversion of chromosome
      22, with breakpoints at p11.2 and q13.31 [inv(22)(p11.2q13.31)]. The deleted
      chromosome resulted from a recombinant chromosome inherited from his mother. This
      is a rare case of 22q13 deletion syndrome associated with parental pericentric
      inversion of chromosome 22.

PMID- 18049076
TI  - A patient with de-novo partial deletion of Xp (p11.4-pter) and partial
      duplication of 22q (q11.2-qter).
AB  - We report on a girl with partial deletion of Xp and partial duplication of 22q.
      Family studies demonstrate that both the patient's mother and her nonidentical
      twin sister carry the corresponding balanced translocation;
      46,X,t(X;22)(p11.4;q11.2). This girl has developmental delay, microcephaly, mild
      dysmorphisms and hearing loss but otherwise shows few of the features described
      in individuals with duplications of the long arm of chromosome 22. She does
      manifest characteristics, such as short stature and biochemical evidence of
      ovarian failure, which are seen in partial or complete Xp deletions and Turner's
      syndrome.

PMID- 18049077
TI  - First case reported of Turner syndrome and trisomy 14 chromosomal mosaicism in a
      patient.
AB  - A 25-year-old woman with a mosaic 45,X/47XX,+14 karyotype is reported. She
      presented with short stature, short downward slanting palpebral fissures, broad
      nasal bridge, mouth with downturned corners, short and wide neck, swirly
      hyperpigmentation of the skin, and body asymmetry secondary to right
      hemihyperplasia. As there was an admixture of 45,X and trisomy 14, it was not
      possible to determine the cell line that had the greatest influence on the
      phenotype. We postulate that the proposita's survival until the third decade was
      owing to the chromosomal complementation of both aneuploidy cell lines. To our
      knowledge, this chromosomal association has not been previously reported.

PMID- 18049078
TI  - De-novo balanced translocation between 7q31 and 10p14 in a girl with central
      precocious puberty, moderate mental retardation, and severe speech impairment.
AB  - No causative gene has been found for idiopathic central precocious puberty; and
      FOXP2, located in 7q31, is the only known gene for speech and language
      disturbances. We report a girl with central precocious puberty, moderate mental
      retardation, and severe speech impairment; accompanied by a de-novo balanced
      translocation between 7q31 and 10p14. Physical mapping through molecular
      cytogenetic investigations demonstrated the breakpoints of 7q31 and 10p14 within
      a bacterial artificial chromosome (BAC) clone RP11-124G5 and a cosmid clone
      derived from a BAC clone RP11-1122C18, respectively. FOXP2 was found to be
      localized approximately 500 kb distant from the centromeric end of the disrupted
      BAC RP11-124G5 at the 7q31 breakpoint. Speech impairment in the girl might be
      derived from dysfunction of FOXP2 by a position effect of the 7q31 translocation
      breakpoint.

PMID- 18049079
TI  - Maternal heterodisomy/isodisomy and paternal supernumerary ring of chromosome 7
      in a child with Silver-Russell syndrome.
AB  - Silver-Russell syndrome (SRS) is clinically variable although most cases have
      several common signs. Different chromosomes and chromosomal regions have been
      associated with SRS. Maternal uniparental disomy (UPD) of chromosome 7 is
      responsible for 5-10% of cases, probably because of an imbalance between maternal
      and paternal imprinted genes and more recently maternal duplication or
      epimutations in the 11p15 imprinted region have been described. To date, only two
      patients with maternal UPD7 and a mosaic condition for a supernumerary ring 7
      marker have been reported, and we here report a further case. Standard QFQ
      banding of lymphocytes as well as fluorescence in-situ hybridization analyses
      were performed to identify and characterize the supernumerary marker. UPD testing
      was performed on both the patient's and parents' DNA using chromosome 7
      microsatellite markers. The patient demonstrated a ring in about 4% of the
      analysed cells. On the basis of cytogenetic and molecular results, break points
      were tentatively identified as 7p11.2 and 7q21. Maternal hetero-/iso-UPD and a
      paternal origin for the supernumerary ring were demonstrated. Clinical data
      comparison between our patient who has a SRS phenotype and cases with hetero-/iso
      UPD7 mat and mosaicism for a paternally derived chromosome 7 ring and previously
      reported ring 7 cases suggest that the SRS phenotype is probably because of the
      UPD rather than to the partial trisomy.

PMID- 18049080
TI  - Holoprosencephaly spectrum, ano/microphthalmia, and first branchial arch defects:
      evidence for a new disorder.
AB  - We report on three unrelated Brazilian patients with a holoprosencephaly
      phenotype, with variable central nervous system involvement, ano/microphthalmia,
      and first branchial arch anomalies. The features of these patients show a
      striking similarity to those of the patients reported by Guion-Almeida et al.
      (1999) and Ribeiro et al. (2005), thus confirming the existence of this rare
      condition. All cases are isolated and the etiology remains unknown.

PMID- 18049081
TI  - Fetal megalourethra associated with hypoplastic left heart and imperforate anus:
      a previously unreported association.
AB  - We report two cases of a fetus with a megalourethra associated with a hypoplastic
      left heart, dilated and echogenic bowels, vesico-colonic fistula and an
      imperforate anus. This combination of fetal abnormalities may represent an
      unclassified syndrome.

PMID- 18049082
TI  - Rhizomelia with anal atresia and anophthalmia: a new syndrome?
AB  - We report a newborn who presented with an unreported combination of anophthalmia,
      anal atresia, rhizomelia, dextrocardia and corpus callosum agenesis. Clinical and
      postmortem findings did not match any previously described syndromes with the
      type of anomalies seen in this patient. We suggested that this combination of
      congenital malformations might represent a new syndrome.

PMID- 18049083
TI  - Three siblings with Woodhouse-Sakati syndrome in an Indian family.
AB  - Woodhouse-Sakati syndrome consists of alopecia, hypogonadism, diabetes mellitus,
      mild mental retardation, sensorineural deafness and ECG abnormalities. The
      proband described here has the above-mentioned features and presented with
      idiopathic thrombocytopenic purpura not reported before. Phenotypic variability
      is present in the three affected siblings. The two sisters have hypergonadotropic
      hypogonadism and the brother has hypogonadotropic hypogonadism. Camptodactyly of
      fourth and fifth fingers is seen in proband and her brother. We report for the
      first time three affected siblings of Woodhouse-Sakati syndrome in an Indian
      family.

PMID- 18049084
TI  - Congenital partial lipodystrophy: a new variety with previously undescribed
      clinical features.

PMID- 18049085
TI  - Progressive noninfectious anterior vertebral fusion in a girl with axial
      mesodermal dysplasia spectrum.
AB  - We report a 7-year-old-girl who presented with the clinical criteria of the axial
      mesodermal dysplasia spectrum. Her parents were first cousins. Her facial
      dysmorphism was compatible with Goldenhar syndrome and in addition, she had
      anterior noninfectious vertebral fusions of the cervical and the thoracolumbar
      vertebrae, a congenital dermal sinus and a hypoplastic sacrum. The urogenital and
      the anal-recto regions were normal. To the best of our knowledge, this is the
      first clinical report of a child with axial mesodermal dysplasia in association
      with progressive noninfectious anterior vertebral fusion.

PMID- 18049086
TI  - Sudden death in a patient with mosaic ring X Turner syndrome and a neuronal
      migration disorder.

PMID- 18049087
TI  - A mutation in FGFR2 in a child with Pfeiffer syndrome and a sacral appendage.

PMID- 18049088
TI  - Agnathia-otocephaly complex in a fetus with maternal use of topical 1%
      salicylate.

PMID- 18049089
TI  - The fetal mycophenolate mofetil syndrome.

PMID- 18049090
TI  - Editor's report.

PMID- 18049091
TI  - Added value of PET and PET-CT in oesophageal cancer: a review of current
      practice.
AB  - Oesophageal carcinoma is a relatively rare form of cancer. However, it is also
      one of the most deadly forms of cancer, with a 5-year survival rate of only 3%
      for patients with nodal disease, and 42% for those without nodal disease. It is
      therefore very important to accurately stage the disease at diagnosis and before
      therapy. In this article, we review the role of commonly used investigative
      techniques in the diagnosis and staging of oesophageal carcinoma, with special
      emphasis on PET and PET-CT scanning. The literature is reviewed in the context of
      our recent experience. A retrospective review of 129 patients with oesophageal
      carcinoma, who underwent PET or PET-CT scanning over a 24-month period confirmed
      the incremental value of PET and PET-CT scanning in the staging of oesophageal
      carcinoma.

PMID- 18049092
TI  - The effects of N-butylscopolamine on bowel uptake: an 18F-FDG PET study.
AB  - PURPOSE: To determine the effect of N-butylscopolamine (buscopan) on intestinal
      uptake of 18F-FDG. METHODS: Seventy-two oncology patients were prospectively
      studied and 36 patients received 20 mg of N-butylscopolamine intravenously. All
      patients were imaged with a Siemens PET scanner. After a 4-h fast, patients were
      injected with FDG and then scanned 1 h post-injection. Two experienced observers
      interpreted all studies independently. Scans were scored visually, grading 18F
      FDG bowel uptake (0-3) and the influence of bowel uptake to a lack of confidence
      in scan reporting (0-3). For semi-quantitative comparison, the ratio of
      radiotracer uptake in the bowel to mean liver (B/L) was obtained. RESULTS: All
      results were in favour of N-butylscopolamine. For the qualitative data, a Mann
      Whitney test was used. Results for contribution of bowel uptake to lack of
      confidence in reporting scores, showed P=0.0001 for observer 1, and P=0.002 for
      observer 2; for degree of uptake in bowel scores, observer 1 results gave a value
      of P=0.0001 and observer 2 P=0.001. For agreement of uptake scores, Kappa index
      showed 'moderate' agreement between observers for the control group and 'fair'
      agreement for the N-butylscopolamine group. For contribution of bowel uptake to
      lack of confidence scores, there was 'very good' agreement for the control group
      and 'fair' agreement for the N-butylscopolamine group. The semi-quantitative
      effect of N-butylscopolamine on bowel-to-liver ratio was determined using an
      unrelated t-test that produced significance at the level of P<0.001. CONCLUSION:
      This study showed that administration of N-butylscopolamine can reduce artefacts
      in the bowel during 18F-FDG PET, and can potentially improve accuracy of 18F-FDG
      PET reporting.

PMID- 18049093
TI  - Reduced thalamic 18F-flurodeoxyglucose retention in adults with neurofibromatosis
      type 1.
AB  - OBJECTIVE: Neurofibromatosis type1 (NF1) is associated with cognitive and motor
      deficits whose pathogenesis is not well understood. 18F-Flurodeoxyglucose
      positron emission tomography (FDG PET) might be used to investigate putative
      functional correlates in the brain. METHODS: Whole-body FDG PET including the
      brain had been performed in 29 NF1 patients suspected for malignant peripheral
      nerve sheath tumours (20 females, nine males, age 31.2+/-11.8 years). Twenty-nine
      age-matched and sex-matched subjects without evidence of neurological/psychiatric
      disease in whom FDG PET had been performed for NF1-unrelated oncological
      indication served as controls. Individual brain FDG retention images were
      stereotactically normalized and scaled to a common median retention value within
      the brain. Scaled FDG retention was compared between the NF1 group and the
      control group on a voxel-by-voxel base using ANCOVA in SPM2 with the FDG uptake
      period as covariate. The corrected significance level alpha=0.05 was used. Voxel
      based analysis was complemented by volume of interest (VOI)-based analysis using
      predefined standard VOIs. RESULTS: The voxel-based group comparison revealed a
      significant reduction of scaled FDG retention in the thalamus of the NF1 subjects
      within a cluster of 11.6 ml. There were no further significant effects, neither
      hypo-retention nor hyper-retention. Reduction of relative FDG retention in the
      thalamus in the NF1 subjects was confirmed by VOI analysis. The magnitude of the
      reduction was about 8%. CONCLUSIONS: The thalamus appears to be affected in
      adults with NF1. The observed magnitude of the reduction of scaled thalamic FDG
      retention in adults is smaller than previously reported in children. This may be
      consistent with a stabilization of the disease process with age.

PMID- 18049094
TI  - Active inflammatory bowel disease: head-to-head comparison between 99mTc
      hexamethylpropylene amine oxime white blood cells and 99mTc(V)-dimercaptosuccinic
      acid scintigraphy.
AB  - PURPOSE: Evaluation and comparison between pentavalent 99mTc dimercaptosuccinic
      acid (99mTc(V)-DMSA) and 99mTc-hexamethylpropylene amine oxime white blood cell
      (99mTc-HMPAO WBC) scintigraphy in the detection and assessment of disease
      activity in patients with active inflammatory bowel disease (IBD). MATERIALS AND
      METHODS: 99mTc(V)-DMSA scintigraphy was performed in 23 patients with active IBD
      and true positive 99mTc-HMPAO WBC scintigraphy. Images were considered positive
      when an area of increased uptake was observed. To assess severity of IBD, semi
      quantitative analysis was included with reference to the uptake in the iliac
      crest. Comparison with endoscopic, radiological and clinical data was performed.
      RESULTS: The diagnostic accuracy of 99mTc-HMPAO WBC and 99mTc(V)-DMSA was 91% and
      84%, respectively. A significant correlation between the findings of both
      radioisotopic methods and scintigraphy score was demonstrated. Endoscopic
      findings were significantly correlated with scintigraphic results. Kappa
      statistics showed a moderate to good agreement between the two scintigraphic
      methods. Two patients (8.8%) had negative findings with 99mTc(V)-DMSA
      scintigraphy (false negative results). CONCLUSION: 99mTc(V)-DMSA compared to
      99mTc-HMPAO WBC could provide a simple, non-invasive alternative method for the
      assessment of disease activity, although it is slightly inferior to 99mTc-HMPAO
      WBC scintigraphy especially in the evaluation of disease localization in IBD
      patients.

PMID- 18049095
TI  - Biodistribution study and identification of inflammation sites using 99mTc
      labelled stealth pH-sensitive liposomes.
AB  - PURPOSE: To investigate the biodistribution and the ability of stealth pH
      sensitive liposomes radiolabelled with 99mTc to identify inflammatory regions in
      a rat focal inflammation model. METHODS: Preformed glutathione-containing stealth
      pH-sensitive liposomes were labelled with 99mTc-hexamethylpropylene amine oxime
      (99mTc-HMPAO). The 99mTc-HMPAO radiolabelled stealth pH-sensitive liposomes
      (99mTc-SpHL) were administered intravenously in Wistar male rats with
      inflammation induced by injection subplantar of carrageenan in the right foot. At
      pre-established time intervals the animals were anaesthetized and tissues were
      removed and analysed for 99mTc content using an automatic scintillation
      apparatus. Scintigraphic imaging was also performed after 2, 4 and 8 h of
      intravenous injection of 99mTc-SpHL. RESULTS: The 99mTc-SpHL was significantly
      taken up by the spleen (19.21+/-2.98%ID/g at 30 min post-injection). Low
      radioactivity levels were found in the liver, lungs, and kidney. Moreover, the
      99mTc-SpHL uptake was significantly higher in the inflamed foot when compared to
      the respective control (0.386+/-0.059 and 0.215+/-0.018%ID/g at 2 h post
      injection, respectively). As early as 30 min after administration of 99mTc-SpHL,
      the focus of inflammation could be visualized scintigraphically. The value of the
      inflammatory and non-inflammatory site radioactivity counting ratio was greater
      than 5. CONCLUSION: This result indicates that the 99mTc-SpHL presents a high
      tropism for inflammatory regions and may be useful as a radiopharmaceutical to
      identify these foci.

PMID- 18049096
TI  - 99mTc-HYNIC-rh-annexin-V scintigraphy: visual and quantitative evaluation of
      early treatment-induced apoptosis to predict treatment outcome.
AB  - AIM: To determine the reliability of visual analysis of 99mTc-HYNIC-rh-annexin-V
      tumour uptake (ATU) compared to quantitative tracer uptake evaluation. METHODS:
      Thirty-eight patients (22 male, 16 female, mean age 57) with histologically
      proved lymphoma (n=31), non-small cell lung cancer (NSCLC) (n=4) and head and
      neck squamous cell carcinoma (H&NSCC) (n=3) were examined. 99mTc-HYNIC-rh-annexin
      V scintigraphy (TAS) was acquired before and within 2 days after the start of
      anti-cancer treatment. Maximal counts per pixel in the tumour volume (Cmax) were
      calculated for every target lesion. To match the quantitative and visual ATU,
      both were expressed as a four-grade score. Cmax as percentages of baseline
      values: grade 1, decrease >25%; grade 0, 1-25% decrease; grade 1, 1-25% increase;
      grade 2, >25% increase. Visual analysis: 0=absent, 1=weak, 2=moderate, 3=intense.
      Intra-observer and inter-observer variability and methodological agreement
      between visual and quantitative evaluation of ATU was expressed by computing
      Cohen's kappa statistics. RESULTS: A statistically highly significant correlation
      was found between the changes in ATU and therapy outcome: r=0.97 (P<0.0001) and
      r=0.99 (P<0.0001) for visual and quantitative analysis, respectively. Good intra
      observer reproducibility, with a high kappa of 0.82 for observer 1 and a kappa of
      0.90 for observer 2, was determined. Inter-observer variability was 0.82.
      CONCLUSION: Visual evaluation of ATU after image co-registration appears to be a
      reliable and reproducible method for preliminary assessment of early treatment
      induced apoptosis.

PMID- 18049097
TI  - Evaluation of the effects of toluene inhalation on alveolar epithelial
      permeability by 99mTc-DTPA inhalation scintigraphy in automobile painters.
AB  - BACKGROUND: The main component of paint thinner used in industry is toluene
      diisocyanate (TDI) which can cause occupational asthma in 5-10% of exposed
      workers. AIM: To investigate the effect of TDI on 99mTc clearance rate of
      alveolar epithelium and on pulmonary function tests (PFT) in automobile painters,
      and to determine the relationship between 99mTc-DTPA radioaerosol lung
      scintigraphy and serum levels of antioxidant enzymes and metalloproteinases
      (MMPs) of automobile painters. METHODS: Twenty-eight automobile painters and 13
      control subjects were included in the study. 99mTc-DTPA aerosol inhalation
      scintigraphy and PFT were administered to all subjects. Clearance half-time
      (T1/2) and penetration index (PI) on the first-minute image after 99mTc-DTPA
      scintigraphy were calculated. Blood levels of MDA, antioxidant enzymes and
      metalloproteinases were measured. RESULTS: The mean T1/2 values of automobile
      painters were longer in both smoker and non-smoker subjects, but the difference
      was not significant (P>0.05). Although the PFT values decreased in automobile
      painters, there was no significant difference between each group. Any correlation
      between spirometric measurements and T1/2 or PI values in non-smoking automobile
      painters was not detected. Negative correlation among mean T1/2 value and FVC%
      and FEV1% in smoking automobile painters, and positive correlation between mean
      T1/2 value and MMP-9, GSH-Px levels in non-smoking automobile painters were
      detected. CONCLUSION: Our results suggested that the clearance of 99mTc-DTPA from
      the lungs of automobile painters was slower than in the control group, but the
      difference is not statistically significant. This data also supports the
      observation that TDI occasionally stimulates bronchial changes rather than
      alveolar changes in automobile painters.

PMID- 18049098
TI  - Evaluation of the automatic three-dimensional delineation of caudate and putamen
      for PET receptor occupancy studies.
AB  - OBJECTIVE: PET receptor occupancy studies with a baseline study and an
      intervention study are increasingly used as an aid in dose-finding procedures for
      central nervous system drug development. The aim of this study was to evaluate,
      and confirm the feasibility of two automatic, paired, three-dimensional
      delineation methods of striatal structures (caudate and putamen) for the purposes
      of PET receptor occupancy studies. METHODS: The automatic extraction was done
      with the deformable surface models from PET binding potential images. The
      segmentation result of the baseline study was utilized for segmenting the
      intervention study. The methods were evaluated with Monte Carlo simulated phantom
      images, a test-retest dataset with 11C-raclopride, and two receptor occupancy
      datasets (11C-raclopride and 18F-SPA-RQ). With the test-retest dataset, the
      reproducibility (normalized absolute differences (NAD)) and reliability
      (intraclass correlation coefficient (ICC)) of binding potential values were
      assessed with the proposed methods designed specifically for receptor occupancy
      and compared with the manual segmentation. A similar comparison was also
      performed for the receptor occupancy estimates. RESULTS: In the test-retest
      dataset, the two automatic three-dimensional segmentation methods had mean NADs
      ranging from 2.44 to 5.11% and ICCs from 0.88 to 0.98. The corresponding values
      for the manual two-dimensional segmentation were 3.45 to 6.65% and 0.82 to 0.96
      (NAD differences non-significant). The automatic methods also yielded similar
      receptor occupancy values to the manual segmentation method in a range of high
      and low occupancy values. CONCLUSION: We believe that the automated three
      dimensional segmentation will be useful in enhancing the analysis of large-scale
      PET receptor occupancy studies with high-resolution scanners.

PMID- 18049100
TI  - Reproducibility and repeatability of differential renal function in 4-week-old
      piglets.
AB  - BACKGROUND: Congenital obstructive renal disease often requires a decision early
      in the child's life on whether or not surgery is required. Differential renal
      function (DRF) calculated from the renogram provides important information for
      the correct decision in this process. A recent publication cast doubt as to the
      reliability of the renogram in providing DRF in the young child. AIM: To describe
      the day-to-day variation and reproducibility of the two commonly used agents for
      estimating DRF. METHODS: Within 1 week, 4-week-old pigs each underwent three
      examinations with both 99mTc-DTPA and 99mTc-DMSA. DRF values from the 99mTc-DTPA
      renograms were calculated using both the area under the curve (AUC) and the
      Rutland-Patlak equation. Day-to-day variations in the results using different
      background subtraction methods were analysed using the coefficient of variation
      for each case and the repeatability coefficient for each type of background
      subtraction. RESULTS: DRF calculated from the 99mTc-DMSA studies showed little
      variation, with a coefficient of variation of 3.9% in the worst case. The
      repeatability coefficient calculated from the 99mTc-DTPA studies using the AUC
      technique combined with the background subtraction method giving the least
      variation was 14.9% while using the Rutland-Patlak technique with its best
      background subtraction showed an RC of 9.4%. CONCLUSIONS: The study demonstrates
      that DRF calculated from 99mTc-DMSA studies have low variability and the results
      are highly reproducible in immature pigs. The DRF calculated from 99mTc-DTPA
      renograms failed to show acceptable reproducibility when analysed using either
      the AUC method or the Rutland-Patlak equation.

PMID- 18049099
TI  - Biodistribution and internal dosimetry of the 188Re-labelled humanized monoclonal
      antibody anti-epidemal growth factor receptor, nimotuzumab, in the locoregional
      treatment of malignant gliomas.
AB  - OBJECTIVE: To evaluate the biodistribution, internal radiation dosimetry and
      safety of the 188Re-labelled humanized monoclonal antibody nimotuzumab in the
      locoregional treatment of malignant gliomas. METHODS: Single doses of 370 or 555
      MBq of 188Re-labelled nimotuzumab were locoregionally administered to nine
      patients with recurrent high-grade gliomas, according to an approved dose
      escalation study. SPECT, planar scintigraphy and magnetic resonance images were
      combined for dosimetric and pharmacokinetic studies. Blood and urine samples were
      collected to evaluate clinical laboratory parameters and for absorbed doses
      calculations. Biodistribution, internal dosimetry, human anti-mouse antibody
      response and toxicity were evaluated and reported. RESULTS: The 188Re-nimotuzumab
      showed a high retention in the surgically created resection cavity with a mean
      value of 85.5+/-10.3%ID 1 h post-injection. It produced mean absorbed doses in
      the tumour region of approximately 24.1+/-2.9 Gy in group I (patients receiving
      370 MBq) and 31.1+/-6.4 Gy in group II (patients receiving 555 MBq); the normal
      organs receiving the highest absorbed doses were the kidneys, liver and urinary
      bladder. About 6.2+/-0.8%ID was excreted by the urinary pathway. The maximum
      tolerated dose was 370 MBq because two patients showed severe adverse effects
      after they received 555 MBq of 188Re-nimotuzumab. No patient developed human anti
      mouse antibody response. CONCLUSIONS: A locoregional single dose of 188Re
      labelled nimotuzumab of approximately 370 MBq could be used safely in the routine
      treatment of patients suffering with high-grade gliomas. The efficacy of this
      therapy needs to be evaluated in a phase II clinical trial.

PMID- 18049101
TI  - A profile of Australian nuclear medicine technologist practice.
AB  - BACKGROUND: Nuclear medicine in Australia has encountered significant change over
      the past 30 years, with a move to privately owned practices, technological
      advances and the transfer of education of the nuclear medicine technologist (NMT)
      from technical college apprenticeships to university degrees. Currently,
      shortages of nuclear medicine technologists are reported in some states of
      Australia. It is not known whether changes in NMT practice or the type of centre
      in which an NMT works have an influence on retention of staff. AIM: The primary
      objective of this survey was to establish a profile of NMT practice in Australia,
      with the aim of producing baseline data that could be used in further research to
      establish levels of retention and job satisfaction. METHODS: Chief technologists
      in three states of Australia were invited to respond to a written questionnaire.
      The questionnaire included data about staffing levels, imaging modalities,
      procedures performed, and movement of staff. Findings presented will relate to
      the profile of practice data only. RESULTS: Forty-eight (54%) chief technologists
      responded to the questionnaire with 73% working in privately owned practices. The
      majority of centres employ up to two full-time equivalent nuclear medicine
      technologists and have two gamma cameras and one full-time equivalent nuclear
      medicine physician. Most centres perform a limited range of studies with bone
      scans predominating. More than half the centres make some use of a centralized
      radiopharmacy service. CONCLUSION: Further research is required to determine how
      these changes may impact on workplace satisfaction and in turn, on retention.

PMID- 18049102
TI  - Standardization of LVEF values from MUGA scanning.

PMID- 18049104
TI  - Spontaneous operational tolerance after immunosuppressive drug withdrawal in
      clinical renal allotransplantation.
AB  - Tolerance is the so-called "Holy Grail" of transplantation, but achieving this
      state is proving a major challenge, particularly in the clinical setting. Even in
      rodents, the definition of true transplant tolerance is not applicable to many
      models, with late graft damage often occurring despite long-term graft survival.
      Hence the term "operational tolerance," based more on graft function and absence
      of exogenous immunosuppression, is being adopted. Although the most sought-after
      goal in this field is to intentionally induce this state in a controlled manner,
      translating protocols across species from rodents to the clinic, the current
      literature demonstrates that this is proving a formidable task. A complementary
      approach is to address transplant tolerance from a different angle, by studying
      tolerance-like phenomena that occur "unintentionally" in transplant patients
      after immunosuppressive drug weaning. Such spontaneous operational tolerance,
      which can take place after years of immunosuppression, is rare in kidney
      transplant recipients. However, determining exactly how this state arises and how
      it can be detected may make it possible to induce it in a greater number of
      patients and then to return to the drawing board to rationally design protocols
      that have a greater chance of clinical success. Moreover, the study of such
      patients should help in the identification of biomarkers of low immunological
      risk that could be used to select patients for potential weaning. Collaborative
      efforts through international networks, together with the application of newer
      and more powerful technologies to diagnostic, prognostic, and mechanistic
      research, may help transplanters to achieve this goal.

PMID- 18049105
TI  - Ghrelin, atherosclerosis, and glucose: GAG or causal relationships?

PMID- 18049106
TI  - Tissue-engineered human corneal endothelial cell sheet transplantation in a
      rabbit model using functional biomaterials.
AB  - BACKGROUND: This study was performed to investigate whether transplantation of
      bioengineered human corneal endothelial cell (HCEC) sheet grafts into corneas
      denuded of endothelium could restore corneal function and clarity in a rabbit
      model. METHODS: After being labeled with PKH26 fluorescent dye, the adult HCECs
      derived from eye bank corneas were cultivated on the thermoresponsive poly(N
      isopropylacrylamide) (PNIPAAm)-grafted surfaces for 3 weeks at 37 degrees C, and
      were harvested as transplantable cell sheets after incubation for 45 min at 20
      degrees C. Attached by gelatin hydrogel discs, the bioengineered cell monolayers
      were transplanted to rabbit corneas denuded of endothelium (HCEC sheet group).
      Traumatized rabbit corneas were served as controls. Postsurgical corneas
      underwent clinical observations and histological examinations for 6 months.
      RESULTS: By transmission electron microscopy and Western blot analysis of zonula
      occludens-1 and Na+,K+ -adenosine triphosphatase proteins, the structure and
      function of HCEC sheets resembled those of native corneal endothelium. After
      endothelial cells were removed, corneas of each group turned severe edematous and
      opaque. In the HCEC sheet groups, corneal clarity was gradually restored and
      corneal thickness was significantly less than that in the control groups
      (P<0.05). The attached PKH26-positive HCECs spread on rabbit Descemet's membrane
      after receiving cell sheet grafts. Intraocular delivery of HCEC sheets by means
      of a minimally invasive technique (i.e., small-incision surgery using
      biodegradable hydrogels) demonstrated long-term graft integration with damaged
      corneas. CONCLUSIONS: These results indicate that using cultured HCECs and
      functional biomaterials, PNIPAAm and gelatin, an effective cell sheet-based
      therapy can be developed for the treatment of corneal endothelium deficiency.

PMID- 18049107
TI  - Improvement of the survival rate by fetal liver cell transplantation in a mice
      lethal liver failure model.
AB  - BACKGROUND: The use of cell transplantation as an alternative therapy for
      orthotopic liver transplantation has been widely anticipated due to a chronic
      donor shortage. We previously reported the method used to enrich hepatic
      progenitor cells (HPCs) forming cell aggregations. In this study, we transplanted
      HPCs into the liver injury model mice to determine whether HPC transplantation
      may improve the liver dysfunction. METHODS: We obtained donor cells from E13.5
      fetal livers of green fluorescent protein (GFP) transgenic mice. We transplanted
      GFP-positive fetal liver cells into the transgenic mice which express diphtheria
      toxin (DT) receptors under the control of an albumin enhancer/promoter.
      Subsequently, we induced selective liver injury to recipient mice by DT
      administration. We then evaluated the engraftment of the transplanted cells and
      their effect on survivorship. RESULTS: The low dose of DT induced sublethal liver
      injury and the high dose of DT was lethal to the liver injury model mice. The
      transplanted GFP-positive cells were engrafted into the recipient livers and
      expressed albumin, resembling mature hepatocytes. They continued to proliferate,
      forming clusters. The survival rate at 25 days after transplantation of the cell
      transplanted group (8 of 20; 40.0%) was improved significantly (P=0.0047) in
      comparison to that of the sham-operated group (0 of 20; 0%). CONCLUSIONS: The
      transplanted cells were engrafted and repopulated the liver of recipient mice,
      resulting in the improvement of the survival rate of the liver injury model mice.
      We therefore propose that HPCs are a desirable cell source for cell
      transplantation.

PMID- 18049108
TI  - Association of hypertension genotypes and decline in renal function after kidney
      transplantation.
AB  - BACKGROUND: Polymorphisms of genes such as angiotensin-converting enzyme (ACE),
      angiotensinogen (AGT), and angiotensin receptor type I (AGTR1) have been
      associated with hypertension. Hypertension, in turn, has been associated with
      decreased renal allograft survival. Therefore, this study investigated whether
      single nucleotide polymorphisms (SNPs) in these genes are associated with decline
      in renal function posttransplantation. METHODS: We enrolled patients from a
      prospective cohort of renal transplant recipients of deceased donor kidneys being
      conducted at 9 centers in the Delaware Valley Region. Medical records were
      assessed every 6 months and estimated glomerular filtration rate (eGFR) was
      calculated using the Modification of Diet in Renal Disease equation. Genotypes of
      10, 2, and 5 SNPs in the AGTR1, AGT, and ACE gene were analyzed, respectively.
      RESULTS: The G and the T alleles of the respective AGTR1 SNPs rs275704 and rs5182
      were both associated with 50% decline in eGFR (HR for rs275704: CG=1.22, 95%
      confidence interval [CI] 0.67-2.25 and GG=2.55, 95% CI 1.22-5.32, overall P=0.03;
      HR for rs5182: CT=1.26, 95% CI 0.72-2.19 and TT=3.09, 95% CI 1.50-6.37, overall
      P=0.007) in the adjusted analysis. Similarly, haplotype analysis showed that
      AGTR1 SNPs were associated with 50% decline in eGFR (global P=0.010). The GG
      genotype of SNP rs275704 occurred more frequently in African Americans than in
      non-African Americans (44% vs. 7%, chi2=36.03, P<0.0001). In contrast, the TT
      genotype of SNP rs5182 occurred more frequently in non-African Americans than in
      African-Americans (24% vs. 2%, chi2=21.40, P<0.0001). Polymorphisms in the ACE
      and AGT genes were not associated with renal allograft outcomes. CONCLUSIONS:
      SNPs in AGTR1 gene are associated with decline in renal function
      posttransplantation.

PMID- 18049109
TI  - Ghrelin, glucose homeostasis, and carotid intima media thickness in kidney
      transplantation.
AB  - BACKGROUND: Abnormalities in glucose homeostasis (AGH) frequently occur in kidney
      transplantation and favor vascular lesions. The purpose of this study was to
      analyze whether C-reactive protein (CRP), adiponectin, and ghrelin are markers of
      AGH and indicators of carotid atherosclerosis in kidney transplant patients with
      fasting plasma glucose below 126 mg/dL. METHODS: This was a cross-sectional study
      of 85 kidney transplant patients (59 men; mean age: 52.4 +/- 11.6 years; median
      posttransplant follow-up 31 (range 3-61) months). All patients underwent an oral
      glucose tolerance test. Abnormalities in glucose homeostasis were diagnosed
      following American Diabetes Association criteria. CRP, adiponectin, and ghrelin
      levels were determined. Doppler ultrasound of the carotid artery was performed to
      determine intima media thickness (IMT) and atheromatous plaque. RESULTS: A total
      of 50.5% of patients had AGH (12.9% were diagnosed with new-onset diabetes
      mellitus after transplantation and 37.7% had impaired glucose tolerance or
      impaired fasting glucose), whereas 49.4% were normoglycemic. Patients with AGH
      were older (P=0.002), had greater carotid IMT (P=0.022), and lower ghrelin
      concentrations (P=0.017) than normoglycemic patients. Logistic regression
      analyses showed ghrelin to be an independent marker for AGH (P=0.012) and AGH to
      be related to greater IMT (P=0.041). No differences in adiponectin or CRP were
      found in relation to AGH or atherosclerosis; however, there was a positive
      correlation between adiponectin levels and prednisone dose (r=0.240; P=0.044).
      CONCLUSIONS: A total of 50.5% of the study patients had abnormalities in glucose
      homeostasis. Patients with AGH had a higher percentage of preclinical
      atherosclerosis (greater carotid IMT). Ghrelin is an independent marker for
      abnormalities in glucose homeostasis.

PMID- 18049110
TI  - Relevant factors to psychological status of donors before living-related liver
      transplantation.
AB  - BACKGROUND: While previous surveys have demonstrated the psychological impact on
      living-related liver transplantation (LRLT) donors, such as anxiety, depression,
      ambivalence and anger, the details regarding the relevant factors that affect
      donors' psychological status have not been well described. METHODS: To evaluate
      environmental factors, 66 donors were interviewed to obtain information regarding
      donors' decision-making motivation, process, conflicts, and internal pressure
      about donation just before surgery. To determine the donors' psychological
      status, they completed the State-Trait Anxiety Inventory, Beck Depression
      Inventory, and World Health Organization Quality of Life 26 standardized
      psychological tests for anxiety, depression, and quality of life (QOL).
      Respective recipients completed the same tests separately, in order to determine
      psychological synchronization with the donors. With regard to motivation, donors
      were divided into two groups, and further divided into three groups based on
      processes. Donors were also sorted in groups of those "with conflict" and "with
      pressure." Their psychological test results were compared within groups, as well
      as with those from recipients. RESULTS: Donors from the nonvolunteer or
      postponement groups were significantly more anxious and depressed than other
      donors. Donors from the "with conflict" or "with pressure" groups were
      significantly more anxious, more depressed, and had worse QOL. There was a
      significant positive correlation between donors' and recipients' test results for
      anxiety and QOL, especially when donors belonged to the volunteer group.
      CONCLUSIONS: Our results suggest that donors' decision-making process and
      recipients' psychological status, especially donors' state anxiety should be
      considered when assessing donors' psychological status before LRLT.

PMID- 18049112
TI  - Lower expression of Nrf2 mRNA in older donor livers: a possible contributor to
      increased ischemia-reperfusion injury?
AB  - BACKGROUND: The cellular mechanisms involved in mediating cytoprotection against
      ischemia-reperfusion (IR) injury are not well understood. In animal models, NF-E2
      related factor-2 (Nrf2) protects against IR injury by transcriptional activation
      of phase II antioxidants. Here, we investigate how the expression of Nrf2 mRNA in
      human donor livers in the setting of liver transplantation (LT) correlates with
      the histological damage associated with IR injury and whether or not this
      influences the outcome of LT. METHODS: Pairs of biopsies were acquired from 14
      donor livers; the first biopsy of each pair was taken at the start of the
      retrieval operation, prior to the IR phase of LT and the second at the end of
      transplantation. RNA was extracted from snap frozen tissue and cDNA was prepared.
      Nrf2 mRNA expression was determined using real-time polymerase chain reaction
      (PCR). The modified Suzuki scoring system was used for histological grading of IR
      injury and relevant donor, recipient, and after LT clinical data were compiled.
      RESULTS: Nrf2 expression was observed in all biopsies, both before and after IR.
      Some donor organs had greater expression of Nrf2 mRNA before IR injury, and these
      organs had lower Suzuki scores and better liver functions (ALT) after LT. Donors
      of livers with greater Nrf2 levels were significantly younger (40.5 yrs, range 28
      53 yrs) than those with low Nrf2 levels (55.5 yrs, range 48-61 yrs), P<0.05.
      CONCLUSION: Livers from older donors have lower levels of Nrf2 perhaps exposing
      these organs to more IR-related damage.

PMID- 18049111
TI  - Angiogenesis soluble factors as hepatocellular carcinoma noninvasive markers for
      monitoring hepatitis C virus cirrhotic patients awaiting liver transplantation.
AB  - BACKGROUND: Physiological angiogenesis occurs during liver regeneration, leading
      to the formation of new functional sinusoids. Pathological angiogenesis occurs in
      hepatocellular carcinoma (HCC). We aimed to evaluate the expression of angiogenic
      factors in hepatitis C virus (HCV)-HCC tissues and the utility of angiogenesis
      soluble factors as noninvasive markers of HCC and tumor growth. METHODS: Thirty
      eight HCV-HCC tumors with 10 corresponding nontumor cirrhotic tissues, as well as
      42 independent HCV cirrhotic and 6 normal liver tissues were studied using high
      density oligonucleotide arrays. Human angiogenesis microarray was used for the
      protein detection of EGF, TIMP-1, TIMP-2, HGF, angiopn-1, angiopn-2, VEGF-A, IP
      10, PDGF, KGF, angiogenin, VEGF-D, ICAM-1, and FGF in plasma samples from 40
      patients (30 HCCs and 10 HCV cirrhosis). RESULTS: From the gene expression
      analysis of the HCV-HCC tumors compared to normal livers, we found an important
      number of genes related to angiogenesis differentially expressed (alpha=0.01),
      including VEGF, PDGF, AGPTL2, ANG, EGFL6, EGFR, angiopn-1, angiopn-2, ICAM2, TIMP
      2, among others. Moreover, angiogenic genes were also differentially expressed
      when HCV-HCC samples were compared to HCV cirrhotic tissues (alpha=0.01; VEGF,
      EGFL3, EGFR, VEGFB, among others). Ten out of 14 angiogenic proteins analyzed
      were statistically differentially expressed between HCV cirrhosis and HCV-HCC
      groups (TIMP-1, TIMP-2, HGF, angiopn-1, angiopn-2, VEGF-A, IP-10, PDGF, KGF, and
      FGF; P<0.05). In addition, we observed that angiopn-2 was the most significant
      predictor (area under the curve: 0.83). CONCLUSION: Differentially expressed
      angiogenesis genes were observed between HCV patients with and without HCC.
      Soluble angiogenic factors might be useful for monitoring high-risk HCV patients.

PMID- 18049113
TI  - Toll-like receptor 4 mediates the early inflammatory response after cold
      ischemia/reperfusion.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury leads to graft dysfunction and may
      contribute to alloimmune responses posttransplantation. The molecular mechanisms
      of cold I/R injury are only partially characterized but may involve toll-like
      receptor (TLR)-4 activation by endogenous ligands. We tested the hypothesis that
      TLR4 mediates the early inflammatory response in the setting of cold I/R in a
      murine cardiac transplant model. METHODS: Syngeneic heart transplants were
      performed in mutant mice deficient in TLR4 signaling (C3H/HeJ) and wild-type mice
      (C3H/HeOuJ). Transplants were also performed between the strains (mutant hearts
      into wild-type recipients and the converse). Donor hearts were subjected to 2 hr
      of cold ischemia. The grafts were retrieved at 3 and 24 hr after reperfusion.
      Serum samples were collected for cytokine analysis. Reverse-transcription
      polymerase chain reaction and histologic analysis were used to assess intra-graft
      inflammation. RESULTS: After transplant, serum tumor necrosis factor (TNF),
      interleukin (IL)-6, JE/monocyte chemotractant protein (MCP)-1, IL-1beta, and
      troponin I levels, as well as intragraft TNF, IL-1beta, IL-6, early growth
      response (EGR)-1, intercellular adhesion molecule (ICAM)-1, and inducible nitric
      oxide synthase (iNOS) mRNA levels, were significantly lower in the mutant-
      >mutant group compared to the wild-type-->wild-type group (P< or =0.05).
      Intermediate levels of serum IL-6, JE/MCP-1, as well as intragraft TNF, IL-1beta,
      IL-6, and ICAM-1 mRNA were observed after transplants in the mutant-->wild-type
      and wild-type-->mutant groups. Immunohistochemistry revealed less myocardial
      nuclear factor-kappaB nuclear translocation at and less neutrophil infiltration
      in the mutant-->mutant group compared to the wild-type-->wild-type group.
      CONCLUSIONS: These findings demonstrate that TLR4 signaling is central to both
      the systemic and intragraft inflammatory responses that occur after cold I/R in
      the setting of organ transplantation and that TLR4 signaling on both donor and
      recipient cells contributes to this response.

PMID- 18049114
TI  - Prolongation of survival of fully allogeneic cardiac grafts and generation of
      regulatory cells by a histamine receptor 2 antagonist.
AB  - BACKGROUND: The effects of histamine on immunologic responses via the histamine
      receptor 2 (HR2) have been studied, but few investigations explored the
      immunomodulatory role of histamine in vivo. We examined whether the HR2
      antagonist ranitidine affects the alloimmune response in a murine model of
      cardiac transplantation. METHODS: CBA (H-2k) recipients were given no treatment
      or one intravenous injection of ranitidine on the day of transplantation of a
      heart from C57BL/10 (H-2b) donors. Survival of the allografts was recorded. The
      effect of the ranitidine treatment on cell proliferation and cytokine production
      was assessed by mixed leukocyte culture and enzyme-linked immunosorbent assays.
      An adoptive transfer study was conducted to determine whether regulatory cells
      were generated. The effect on graft survival of adding FK506 to the ranitidine
      treatment was also examined. RESULTS: CBA recipients given ranitidine (60 mg/kg)
      had prolonged graft survival (median survival time [MST], 87 days). Ranitidine
      treatment also suppressed the proliferation of splenocytes and production of
      interleukin (IL)-2 and up-regulated IL-10 production. Adoptive transfer of
      splenocytes and CD4 cells from ranitidine-treated allograft recipients induced
      significant prolongation of allograft survival in naive secondary recipients
      (MST, 71 and >100 days, respectively). CBA recipients given both ranitidine and
      FK506 (0.1 mg/kg/day for 14 days) had indefinite survival of cardiac allografts
      (MST, >100 days). CBA recipients treated with FK506 alone rejected the allografts
      (MST, 27 days). CONCLUSION: In our model, ranitidine treatment induced
      significantly prolonged survival of fully allogeneic cardiac grafts, generated
      CD4 regulatory cells, and indefinite survival when combined with FK506 (0.1
      mg/kg/day).

PMID- 18049115
TI  - Peptide-dependent inhibition of alloreactive T-cell response by soluble divalent
      HLA-A2/IgG molecule in vitro.
AB  - BACKGROUND: Induction of peripheral tolerance in an antigen-specific manner is a
      critical goal of transplant biology. The specificity and avidity of multimerized
      peptide/major histocompatibilty complexes suggest their potential ability to
      modulate antigen-specific T-cell sensitization and effector functions. METHODS: A
      soluble divalent HLA-A2/IgG molecule (HLA-A2 dimer) was constructed and loaded
      with a self-protein origin peptide (Tyr(368-376)) to form a divalent Tyr/HLA-A2
      molecule (Tyr/HLA-A2 dimer), which allowed for specific targeting to the epitope
      specific cytotoxic T lymphocytes in bulk alloreactive T cells. Alloreactive T
      cell response was induced by coculture of Tyr(368-376) -pulsed T2 cells (T2/Tyr)
      with peripheral blood lymphocytes of HLA-A2-negative (HLA-A2-ve) sample; five
      samples of HLA-A2-ve individuals were included in this study. After the coculture
      in the presence of Tyr/HLA-A2 dimer, the suppression of the dimer on alloresponse
      was characterized by analyzing allogeneic T-cell proliferation, specific
      cytolytic activity against the T2/Tyr, and specific Tyr/HLA-A2 tetramer staining.
      RESULTS: The Tyr/HLA-A2 dimer suppresses alloreactive T-cell response by
      inhibiting its proliferation and cytotoxicity against specific target T2/Tyr in
      vitro, and it is interesting that the suppression is peptide-specific. The
      Tyr/HLA-A2 tetramer staining suggests the reduced function of CD8+ T cell is
      caused by inhibiting the generation of the epitope-specific alloreactive T cells
      by the Tyr/HLA-A2 dimer in three samples. Moreover, the existence of epitope
      specific but function-negative T cells in the other two samples suggests that
      another mechanism might exist that is involved in silencing alloreactive
      responses by the dimer. CONCLUSION: Peptide-loaded dimers offer a novel approach
      to induce peptide-specific immunosuppression and may be useful in promoting graft
      survival.

PMID- 18049116
TI  - Ischemic central necrosis in pockets of transplanted myoblasts in nonhuman
      primates: implications for cell-transplantation strategies.
AB  - BACKGROUND: Several cell-transplantation strategies implicate the injection of
      cells into tissues. Avascular accumulations of implanted cells are then formed.
      Because the diffusion of oxygen and nutrients from the surrounding tissue
      throughout the implanted cell accumulations may be limited, central ischemic
      necrosis could develop. We analyzed this possibility after myoblast
      transplantation in nonhuman primates. METHODS: Macaca monkeys were injected
      intramuscularly with different amounts of myoblasts per single site. These sites
      were sampled 1 hr later and at posttransplantation days 1, 3, 5, and 7 and
      analyzed by histological techniques. RESULTS: One day posttransplantation, the
      largest pockets of implanted cells showed cores of massive necrosis. The width of
      the peripheral layer of living cells was approximately 100-200 microm. We thus
      analyzed the relationship between the amount of myoblasts injected per site and
      the volume of ischemic necrosis. Delivering 0.1 x 10(6) and 0.3 x 10(6) myoblasts
      did not produce ischemic necrosis; pockets of 1 x 10(6), 3 x 10(6), 10 x 10(6),
      and 20 x 10(6) myoblasts exhibited, respectively, a mean of 2%, 9%, 41%, and 59%
      of central necrosis. Intense macrophage infiltration took place in the muscle,
      invading the accumulations of necrotic cells and eliminating them by
      posttransplantation days 5 to 7. CONCLUSIONS: The desire to create more neoformed
      tissue by delivering more cells per injection site is confronted with the fact
      that the acute survival of the implanted cells is restricted to the peripheral
      layer that can profit of the diffusion of oxygen and nutriments from the
      surrounding recipient's tissue.

PMID- 18049117
TI  - Role of intra-islet endothelial cells in islet allo-immunity.
AB  - BACKGROUND: Intra-islet endothelial cells (IECs) express high levels of major
      histocompatibility complex (MHC) and are pivotal for posttransplant islet
      revascularization. We postulated that donor-specific sensitization would result
      in hyperacute rejection of IECs and prevent islet engraftment. Furthermore,
      ligation of endothelial cells with subsaturating concentrations of anti-MHC class
      I antibody (Ab) results in "accommodation" conferring protection against
      Ab/complement-mediated lysis. Therefore, we investigated whether accommodation of
      IECs would prevent hyperacute rejection of islets in sensitized recipients.
      METHODS: Islets were transplanted beneath the kidney capsule and allograft
      survival monitored using daily blood glucose (diabetes >300 mg/dL, normoglycemia
      <150 mg/dL). Recipients were presensitized with donor islets, splenocytes, or
      skin. Accommodation was induced by incubating human or murine islets with varying
      concentrations of anti-MHC class I Ab ex vivo. RESULTS: Isografts remained
      functional for >100 days, whereas allografts were rejected by day 14. Islet allo
      transplantation induced donor-specific but not third-party anti-MHC Abs. Donor
      specific, but not third-party, sensitization induced hyperacute rejection of
      subsequent islet allografts (median survival 1 day) associated with complement
      deposition. Preincubation of islets with subsaturating concentrations of anti-MHC
      I Abs (1-100 ng/mL) up-regulated Bcl-2, Bcl-xl, and HO-1 within CD31+ IEC. These
      accommodated islets were resistant against hyperacute rejection when transplanted
      into donor-(splenocyte) sensitized recipients without any immunosuppression
      (median survival 6 days). CONCLUSIONS: Pretransplant sensitization against donor
      antigens results in hyperacute rejection of murine islets. IECs may play a
      crucial role in development of donor-specific immunity after islet
      transplantation. Significantly, accommodation of IEC may confer resistance to
      hyperacute rejection in sensitized recipients.

PMID- 18049118
TI  - The involvement of FcR mechanisms in antibody-mediated rejection.
AB  - BACKGROUND: Antibody-mediated rejection is characterized by macrophage
      margination against vascular endothelium. The potential interactions triggered by
      antibodies between endothelial cells (EC) and macrophages have not been examined
      thoroughly in transplants. We used in vivo and in vitro models of antibody
      mediated rejection. METHODS: Passive transfer of monoclonal alloantibodies (Allo
      mAbs) to donor major histocompatibility complex-class I antigens was used to
      restore acute rejection of B10.A (H-2a) hearts to C57BL/6 (H-2b) immunoglobulin
      knockout (IgKO) recipients. Intragraft cytokine mRNA expression was measured by
      real-time polymerase chain reaction. In vitro, mouse EC were cultured in the
      presence of Allo-mAbs to donor major histocompatibility complex class I antigens
      and mononuclear cells. Levels of cytokines in culture supernatants were
      determined in enzyme-linked immunosorbent assay. RESULTS: Expression of MCP-1, IL
      6 and IL-1alpha mRNA was higher in rejecting transplants from recipients treated
      with Allo-mAbs compared to non-rejecting transplants. EC sensitized with Allo
      mAbs produced high levels of MCP-1 and KC. The addition of macrophages to
      sensitized EC stimulated high levels of IL-6 in addition to MCP-1, KC, Rantes,
      and TIMP-1. The levels of MCP-1 and IL-6 were significantly lower in co-cultures
      of EC sensitized with IgG1 Allo-mAbs in the presence of mononuclear cells from
      Fcgamma-Receptor III KO (FcgammaRIII-KO) graft recipients compared to co-cultures
      with wild-type cells. The levels of both cytokines were also lower in co-cultures
      of EC stimulated with F(ab')2 fragments of antibody. CONCLUSIONS: Our findings
      indicate that IgG1 Allo-mAbs to major histocompatibility complex class I antigens
      can augment graft injury by stimulating EC to produce MCP-1 and by activating
      mononuclear cells through their Fc receptors.

PMID- 18049119
TI  - Recipient-derived neoangiogenesis of arterioles and lymphatics in quilty lesions
      of cardiac allografts.
AB  - BACKGROUND: The contribution of extracardiac cells to tissue turnover in heart
      allografts has recently been demonstrated. Complex subendocardial infiltrates,
      known as Quilty lesions, are frequently observed in cardiac allografts. The
      origin of the different cellular components of Quilty lesions is not known.
      METHODS: Different constituents of these lymphonodular infiltrates were analyzed
      with regard to donor or recipient derivation. Laser-assisted microdissection with
      subsequent short tandem repeat polymerase chain reaction (PCR)-based "genetic
      fingerprinting" was employed. Combined immunofluorescence and fluorescence in
      situ hybridization for sex chromosomes was performed for confirmation in cases of
      gender-mismatched transplantation. Expression of angiogenic factors (FGF-2, PDGF
      alpha, PDGF-alpha-receptor, and VEGF-alpha) was analyzed by quantitative real
      time reverse-transcription PCR and immunohistochemistry. RESULTS: The
      inflammatory, nonvascular component of Quilty lesions was completely recipient
      derived. Blood vessels were of mixed origin. Different compartments of blood
      vessels displayed different rates of recipient derivation (endothelium up to 50%,
      smooth muscle cells up to 15%). Lymphatic vessels were mainly recipient-derived.
      Of the angiogenic molecules, VEGF-alpha expression was significantly increased in
      the adjacent myocardium, compared to controls and the Quilty lesions themselves.
      CONCLUSIONS: The inflammatory compartment of Quilty lesions is of recipient
      origin and shows chimeric neoangiogenesis of blood and lymphatic vessels. VEGF
      alpha produced in the adjacent myocardium appears to stimulate the chimeric
      neoangiogenesis.

PMID- 18049120
TI  - Infection of human endothelium in vitro by cytomegalovirus causes enhanced
      expression of purinergic receptors: a potential virus escape mechanism?
AB  - BACKGROUND: Human cytomegalovirus (CMV) uses different strategies to escape from
      human host defense reactions. Previously we have observed that infection of
      endothelial cells with CMV in vitro leads to enhanced activity of endothelial
      ectonucleotidases. These ectoenzymes are responsible for hydrolysis of
      extracellular adenine nucleotides, resulting in the formation of adenosine.
      Infection with CMV in vivo therefore may result in local increase of adenosine
      production, providing an anti-inflammatory and antiaggregatory microenvironment,
      which may facilitate entry of the virus into the target cell. METHODS: The
      present study focuses on the expression of P2 type purinergic receptors on
      endothelial cells after infection with CMV. Human endothelial cells were infected
      with CMV and compared with either uninfected cells or endothelial cells infected
      with other herpesviruses (herpes simplex virus [HSV] 1 or 2) for the expression
      of P2 receptors such as P2Y1, P2Y2, or P2X7. For comparison, cells stimulated
      with nonspecific agents were also studied. RESULTS: A strong upregulation of the
      P2 receptors tested was shown, exclusively in CMV-infected cells. Stimulation
      with either HSV-1 or HSV2, nonspecific stimulants, or various cytokines did not
      affect the expression of these P2 receptors significantly. CONCLUSION: Infection
      of endothelium with CMV causes significant upregulation of the P2 receptors
      studied. As these receptors may potentially be able to concentrate nucleotides
      along the ectonucleotidases of the endothelial cell membrane, rapid local
      hydrolysis of adenosine triphosphate and adenosine diphosphate may be facilitated
      by enhanced P2 receptor expression. Such a CMV induced mechanism might enable the
      virus to escape from an important host defense response, such as local
      microthrombus formation.

PMID- 18049121
TI  - Studies on glycolipid antigens in small intestine and pancreas from alpha1,3
      galactosyltransferase knockout miniature swine.
AB  - BACKGROUND: To avoid hyperacute rejection of xeno-organs, alpha1,3
      galactosyltransferase knockout (GalT-KO) pigs have been produced. Galalpha1,3Gal
      determinant elimination may expose cryptic carbohydrate antigens and/or generate
      new antigens. This is the first biochemical study of carbohydrate antigens in
      GalT-KO pig organs. METHODS: Neutral and acidic glycolipids were isolated from
      small intestine and pancreas of two GalT-KO and one wild-type (WT) pig.
      Glycolipid immune reactivity was tested on thin-layer chromatograms. Small
      intestine neutral glycolipids were separated by high-performance liquid
      chromatography and selected fractions were analyzed by proton nuclear magnetic
      resonance spectroscopy. Total gangliosides were quantified on thin-layer
      chromatograms and in microtiter wells. RESULTS: Using Galalpha1,3nLc4 glycolipid
      reference, total Galalpha1,3Gal glycolipid antigens in the WT animal was
      estimated at about 30 microg (small intestine) and 3 microg (pancreas) per gram
      of dry tissue. Galalpha1,3Gal determinants were not detected in GalT-KO tissues
      at a detection limit of less than 0.25% (small intestine) and 0.5% (pancreas) of
      the WT tissues. Isoglobotriaosylceramide (iGb3) was absent but trace amounts of
      Fuc-iGb3 was found in both GalT-KO and WT pig small intestine. Blood group H type
      2 core saccharide compounds were increased in GalT-KO pancreas. Total amount of
      gangliosides was decreased in GalT-KO tissues. The alpha1,3-galactosyltransferase
      acceptor, N-acetyllactosamine determinant, was not increased in GalT-KO tissues.
      Human serum antibodies reacted with WT organ Galalpha1,3Gal antigens and
      gangliosides, of which the ganglioside reactivity remained in GalT-KO tissues.
      CONCLUSIONS: Knockout of porcine alpha1,3-galactosyltransferase gene results in
      elimination of Galalpha1,3Gal-terminated glycolipid compounds. GalT-KO genetic
      modification did not produce new compensatory glycolipid compounds reactive with
      human serum antibodies.

PMID- 18049122
TI  - Acute insulin responses to glucose and arginine as predictors of beta-cell
      secretory capacity in human islet transplantation.
AB  - Islet transplantation for type 1 diabetes can enable the achievement of near
      normal glycemic control without severe hypoglycemic episodes. How much an islet
      (beta-cell) graft may be contributing to glycemic control can be quantified by
      stimulatory tests of insulin (or C-peptide) secretion. Glucose-potentiation of
      arginine-induced insulin secretion provides a measure of functional beta-cell
      mass, the beta-cell secretory capacity, as either AIR(pot) or AIR(max), but
      requires conduct of a hyperglycemic clamp. We sought to determine whether acute
      insulin responses to intravenous glucose (AIR(glu)) or arginine (AIR(arg)) could
      predict beta-cell secretory capacity in islet recipients. AIR(arg) was a better
      predictor of both AIR(pot) and AIR(max) (n=10, r2=0.98, P<0.0001 and n=7,
      r2=0.97, P<0.0001) than was AIR(glu) (n=9, r2=0.78, P=0.002 and n=6, r2=0.76,
      P=0.02). Also, the measures of beta-cell secretory capacity were highly
      correlated (n=7, r2=0.98, P<0.0001). These results support the use of AIR(arg) as
      a surrogate indicator of beta-cell secretory capacity in islet transplantation.

PMID- 18049123
TI  - Liver transplantation in children with progressive familial intrahepatic
      cholestasis.
AB  - Progressive familial intrahepatic cholestasis (PFIC) is caused by mutations of
      the bile salt export pump or the multidrug resistance P-glycoprotein, resulting
      in chronic hepatic failure. Partial external diversion of bile or ileal bypass is
      effective in some cases and, in others, liver transplantation (OLT) is necessary.
      Forty-two children were included in this study. Twenty-six children suffered from
      PFIC type 2 and 16 from PFIC type 3. Symptoms included pruritus, cholestasis,
      liver cirrhosis, and growth retardation. Seventeen patients received external
      biliary diversion. Ten had to undergo OLT in the following course. As of this
      report, three of the remaining patients were on the wait list for OLT. Twenty
      three children received a liver graft primarily with excellent outcome. Our data
      show that OLT is the option of choice in symptomatic PFIC and whenever liver
      cirrhosis is present. We suggest a very restrictive recommendation of external
      biliary diversion. However, gene therapy may be a future option for children with
      PFIC.

PMID- 18049124
TI  - A rapid method for skin grafting in mice that greatly enhances graft and
      recipient survival.
AB  - A streamlined method of skin grafting in mice is described. This procedure
      eliminates bandages, sutures, and dressings. The elimination of bandages renders
      the overall procedure fast and easy to learn. More importantly, the elimination
      of bandaging results in an increased survival of engrafted mice and a drastic
      reduction in graft displacement. Finally the lack of bandages also makes it
      possible to monitor the graft even in the earliest stages after engraftment.

PMID- 18049125
TI  - Negative and positive co-signaling with anti-BTLA (PJ196) and CTLA4Ig prolongs
      islet allograft survival.
AB  - The novel coinhibitory receptor B and T lymphocyte attenuator (BTLA) has been
      implicated in the regulation of autoimmune and may potentially play a role in
      alloimmune responses. An anti-BTLA monoclonal antibody has been reported to
      prolong fully major histocompatibility complex-mismatched cardiac allograft
      survival, and we test the hypothesis that anti-BTLA monoclonal antibody PJ196 may
      synergize with cytotoxic T lymphocyte antigen-4 immunoglobulin (CTLA4Ig)
      costimulatory blockade in islet transplantation. We investigated the potential of
      PJ196, and show that it did not deplete BTLA expressing cells, but it caused down
      regulation of BTLA on the surface of lymphocytes and accumulation of cells with
      regulatory phenotype at the graft site, promoting islet allograft acceptance
      together with CTLA4Ig. The combination of BTLA coinhibitory modulation and
      CTLA4Ig costimulatory blockade may be an effective adjunctive strategy for
      inducing long-term allograft survival.

PMID- 18049126
TI  - Giant necrotizing abscess of a liver transplant after gunshot injury.

PMID- 18049127
TI  - Successful Hepatitis C Eradication With Preservation of Renal Function in a
      Liver/kidney Transplant Recipient Using Pegylated Interferon and Ribavirin.

PMID- 18049128
TI  - The critical role of histology in an era of genomics and proteomics: a commentary
      and reflection.
AB  - The role of histologic examination in lymphoma diagnosis has been called into
      question by proponents of new technologies, such as genomics and proteomics. We
      review the history and salient features of morphologic evaluation in lymphoid
      diseases, and discuss the general and specific limitations of mature ancillary
      techniques, such as immunohistochemistry, flow cytometry, and molecular studies.
      We then speculate on the future relationship between morphology and the new
      genomic and proteomic technologies as they become integrated into clinical
      practice.

PMID- 18049129
TI  - Anatomy of the anterior prostate and extraprostatic space: a contemporary
      surgical pathology analysis.
AB  - Over 25 years ago, McNeal described a model of prostatic zonal anatomy based on
      autopsy dissections in various planes. As opposed to the cone-shaped organ seen
      in vivo, radical prostatectomy specimens are typically spherical, owing to tissue
      contraction at surgical removal and subsequent processing. Sectioning from apex
      to base yields topography at the Surgical Pathology "sign-out" that may vary from
      McNeal's descriptions. There are no in depth studies of anterior prostatic
      anatomic variability, including the periurethral region, peripheral (PZ) and
      transition (TZ) zones, anterior fibromuscular stroma (AFMS), and anterior
      extraprostatic space (EPS) using modern prosecting techniques. Detailed analysis
      of 197 entirely submitted, whole-mounted radical prostatectomy specimens focused
      on differences in zonal anatomy from apex through base, the relationship of AFMS
      to PZ and TZ, and the nature of the anterior EPS revealed features that may have
      significant impact on determination of zonal origin and pathologic staging of
      anteriorly situated prostate cancer. Among these observations are the predominant
      nature of the anterior PZ at the apex and the potential for its broad contact
      with the AFMS at this location, the differing volumes and location of the TZ in
      prostates with and without benign prostatic hyperplasia, and the composition of
      the anterior EPS, including adipose tissue, blood vessels, and skeletal muscle at
      the apex varying to include medium to large smooth muscle bundles at the base.

PMID- 18049130
TI  - The role of tissue microarrays in prostate cancer biomarker discovery.
AB  - Tissue microarrays (TMAs) offer the potential to rapidly translate genomics and
      basic science research findings to practical clinical application. This is
      particularly true in the field of cancer biomarker research, where TMAs can be
      used for candidate biomarker validation and association with patient clinical,
      pathologic, and outcomes parameters. In this review, we examine the effect of TMA
      use on prostate cancer biomarker research, focusing on the types of TMAs that
      have been used, and the biomarkers that have been examined. The results
      demonstrate that TMAs have been very effective in screening candidate biomarkers
      for subsequent, extended evaluation in large patient populations. In addition,
      the use of TMAs in multiple biomarker series allows for the statistical analysis
      of sets of biomarkers as diagnostic or prognostic tests. The processes used here
      can be applied to any tumor type to improve patient diagnosis, prognosis, and
      treatment response prediction.

PMID- 18049131
TI  - Triple negative breast carcinoma and the basal phenotype: from expression
      profiling to clinical practice.
AB  - Triple negative breast carcinomas (TNBCs) are a group of primary breast tumors
      with aggressive clinical behavior. Most TNBCs possess a basal phenotype (BP) and
      show varying degrees of basal cytokeratin and myoepithelial marker expression.
      The importance of recognizing these tumors came to light largely as the result of
      gene expression profiling studies that categorized breast cancer into 3 major
      groups. Two of these groups are defined by their respective expression of
      estrogen receptor and HER2. TNBCs represent a third group and are defined by
      negativity for hormone receptors and HER2. TNBCs currently lack effective
      targeted therapies and are frequently resistant to standard chemotherapeutic
      regimens. These tumors tend to occur in premenopausal women and members of
      specific ethnic groups and a subset are associated with heritable BRCA1
      mutations. For patients with sporadic TNBCs and BP tumors, BRCA1 dysfunction
      seems to play a major role in the development and progression of disease. The
      pathologist's role in the diagnosis and characterization of TNBCs and BP tumors
      is currently being defined as we are acquiring knowledge of the biologic and
      genetic underpinnings that drive this heterogeneous group of diseases. This
      review will provide a historical prospective on TNBCs and tumors that express
      basal cytokeratins and myoepithelial makers. Additionally, we will discuss the
      molecular biologic, genetic and pathologic aspects of these tumors. Guidelines
      will be provided on how to best approach the diagnosis of these cases and on what
      input pathologists should provide clinicians to help develop optimal therapeutic
      and preventative strategies against this aggressive group of breast cancers.

PMID- 18049132
TI  - Gastrointestinal malignancies in HIV-infected or immunosuppressed patients:
      pathologic features and review of the literature.
AB  - The gastrointestinal (GI) tract is a common internal organ to be involved by
      human immunodeficiency virus (HIV)-related malignancies. It is the second most
      common site for Kaposi sarcoma after skin, and the commonest visceral site, for
      Kaposi sarcoma in AIDS patients. GI lymphomas have been documented in
      approximately 25% of AIDS patients with systemic lymphomas. Moreover, GI
      involvement of AIDS-lymphoma has been associated with poor prognosis and short
      survival. Several other malignancies that occur in the GI tract are also closely
      related to HIV-infected or immunosuppressed individuals; these include
      posttransplant lymphoproliferative disorder, Epstein-Barr virus-associated smooth
      muscle tumors, anal precancerous lesions, and squamous cell carcinoma. As a
      result of active antiretroviral therapy, patients infected with HIV are living
      longer and are consequently at increased risk for development of cancer.
      Therefore, it is possible that the number of AIDS-associated malignancies will
      rise and the pattern of tumors may change in the future. In this paper, the
      clinicopathologic features of GI malignancies associated with AIDS patients are
      reviewed and the differential diagnosis with other mimic lesions is discussed.

PMID- 18049134
TI  - State-of-the-science on postacute rehabilitation: setting a research agenda and
      developing an evidence base for practice and public policy: an introduction.
AB  - The Rehabilitation Research and Training Center on Measuring Rehabilitation
      Outcomes and Effectiveness along with academic, professional, provider,
      accreditor, and other organizations, sponsored a 2-day State-of-the-Science of
      Post-Acute Rehabilitation Symposium in February 2007. The aim of this symposium
      was to serve as a catalyst for expanded research on postacute care (PAC)
      rehabilitation so that health policy is founded on a solid evidence base. The
      goals were to (1) describe the state of our knowledge regarding utilization,
      organization, and outcomes of postacute rehabilitation settings, (2) identify
      methodologic and measurement challenges to conducting research, (3) foster the
      exchange of ideas among researchers, policy makers, industry representatives,
      funding agency staff, consumers, and advocacy groups, and (4) identify critical
      issues related to setting, delivery, payment, and effectiveness of rehabilitation
      services. Plenary presentation and state-of-the-science summaries were organized
      around four themes: (1) the need for improved measurement of key rehabilitation
      variables and methods to collect and analyze this information, (2) factors that
      influence access to postacute rehabilitation care, (3) similarities and
      differences in quality and quantity of services across PAC settings, and (4)
      effectiveness of postacute rehabilitation services. The full set of symposium
      articles, including recommendations for future research, appear in Archives of
      Physical Medicine and Rehabilitation.

PMID- 18049135
TI  - Modified cold pressor test by cold application to the foot after spinal cord
      injury: suggestion of hemodynamic control by the spinal cord.
AB  - OBJECTIVE: Study hemodynamic responses to cold application to the foot (CAF) to
      explore the autonomic cardiovascular control by the spinal cord. DESIGN:
      Controlled experimental study. Hemodynamic variables were measured or calculated
      for 13 healthy subjects, 10 patients with traumatic T4-T6 paraplegia, and 11
      patients with traumatic C4-C7 tetraplegia. Subjects were continuously monitored
      for heart rate (HR), blood pressure (BP), and cerebral blood-flow velocity (CBFV)
      from 5 mins before to 5 mins after 40-120 secs of CAF by ice water foot
      immersion. The recorded signals were digitized online and analyzed offline in the
      time and frequency domains. RESULTS: During CAF, HR increased in the control
      group but decreased in patients (P < 0.001). BP increased significantly in the
      control and tetraplegia groups (P < 0.001) and nonsignificantly in the paraplegia
      group. HR and BP spectral components (LF, HF, LF/HF) did not change
      significantly. CBFV increased significantly in the patient groups (P < 0.05) but
      not in the control subjects. The cerebrovascular resistance increased
      significantly in the control and tetraplegia groups (P < 0.001), but not in the
      paraplegia group. CONCLUSIONS: The findings support the presence of hemodynamic
      autonomic control by the spinal cord and show that responses to CAF can be used
      to assess its integrity.

PMID- 18049136
TI  - Ultrasonographic examination on patients with chronic wrist pain: a retrospective
      study.
AB  - OBJECTIVE: To describe the results of ultrasonographic examination in a series of
      patients with chronic wrist pain and to define the proportion of occult carpal
      ganglion in these patients. DESIGN: A retrospective study including 57 patients
      with wrist pain consecutively referred for sonographic examination. The inclusion
      criteria for this study were a history of wrist pain longer than 3 mos with no
      wrist trauma, and no palpable mass at the wrist. Ultrasound examination with a 10
      MHz linear transducer was used to detect wrist pathology. A well-demarcated
      anechoic mass with posterior enhancement and without vascularity within the mass
      on sonography was defined as a ganglion cyst. RESULTS: Thirty-three of the 57
      patients (58%) were diagnosed by sonographic examination as having a ganglion in
      the wrist joint. The size of the ganglion demonstrated on sonographic imaging
      ranged from 2 x 5 mm to 10 x 9 mm on a longitudinal scan of the wrist (with a
      mean of 4 x 7 mm.). Surgical excision was carried out in 12 patients who had
      ganglions diagnosed by sonographic examination; in all cases, the mucin content
      of the specimen was demonstrated. Eight patients underwent local aspiration
      followed by steroid injection under the guidance of ultrasound. The aspirated
      content was a jelly-like substance. In these 20 treated patients, symptoms of
      wrist pain improved after intervention. CONCLUSIONS: The prevalence of occult
      carpal ganglion is common in chronic wrist pain patients. High-resolution
      sonographic examination facilitates early detection of occult carpal ganglion.

PMID- 18049137
TI  - Reports from spinal cord injury patients: eight months after the 2003 earthquake
      in Bam, Iran.
AB  - OBJECTIVE: The World Health Organization defines disaster as a sudden ecologic
      phenomenon of sufficient magnitude to require external assistance. On December
      26, 2003, the Bam earthquake left more than 200 spinal cord injury (SCI)
      patients. Our study of these SCI patients and the rehabilitation of disabled
      persons in Bam may assist in the organization of rehabilitation programs during
      future disasters. DESIGN: Eight months after the disaster, we planned to visit
      the SCI patients in Bam. We visited 61 patients in Bam, Baravat, and surrounding
      villages. We completed a questionnaire during our visit. RESULTS: The patients'
      mean age was 31.9 +/- 9.6 yrs. Twenty-nine (53.7%) patients were female, and 25
      (46.3%) were male. Fifty-two (96.3%) patients had pain syndromes, which had
      started from 3 days to 8 mos after injury. Thirty-three (61%) patients used clean
      intermittent catheterization, and 29 (53.7%) did not have bowel programs.
      Nineteen (35.2%) patients had pressure sores. CONCLUSIONS: All aspects of
      disasters should be considered seriously by all countries. The special needs of
      people with disabilities during and long after any disaster are important. The
      impact of disasters on disabled people is magnified because of their condition,
      so special attention must be paid to this group.

PMID- 18049138
TI  - Gender differences regarding career issues and promotion in academic physical
      medicine and rehabilitation.
AB  - OBJECTIVE: To assess gender differences in academic progress and attitudes toward
      promotion in academic physical medicine and rehabilitation (PM&R). DESIGN: A
      survey was sent to members of the Association of Academic Physiatrists (AAP).
      Questions addressed demographics, job description, hours worked, childcare
      responsibilities, publications, career aspirations, mentoring, and familiarity
      with promotion and tenure policies. Respondents were also asked about the
      relative importance of career aspects including the perceived benefits of and
      obstacles to promotion. Responses were anonymous. RESULTS: Women spent less time
      on scholarly activities. Women considered the fact that they disliked writing and
      did not know how to do research to be more important obstacles to promotion than
      did men. Women were more likely to have part-time appointments and lower academic
      rank. They had fewer children at home but greater responsibility for child care.
      Women were less likely to aspire to become full professor, they met less often
      with their department chair/supervisor, and they published fewer papers. Men and
      women reported equal career satisfaction. CONCLUSIONS: There are several gender
      differences in the values, attitudes, and priorities in academic PM&R. Women
      respondents were generally less interested in traditional academic pursuits than
      were their male counterparts.

PMID- 18049139
TI  - Assessment of musculoskeletal examination skills: physiatry residents as
      evaluators and models.
AB  - OBJECTIVE: To evaluate the musculoskeletal examination (MSKE) skills of junior
      (postgraduate year [PGY] 2) physical medicine and rehabilitation (PM&R) residents
      and self-confidence with these skills, and to demonstrate changes in self
      confidence in the MSKE skills of senior (PGY3 and PGY4) residents, who served as
      evaluators and models. DESIGN: Forty-one PGY2-4 residents participated in this
      retrospective cohort study, which was conducted within a residency program
      affiliated with two medical schools. Senior residents attended an instructional
      session in performing and evaluating MSKE skills, taught by a musculoskeletal
      physiatrist. The following week, junior residents were tested on their MSKE
      skills; nine seniors served as models, and another nine served as evaluators. Six
      seniors attended the instructional session only and did not participate in the
      evaluation. Juniors received a posttest teaching session on MSKE skills, before
      an unannounced repeat evaluation 5 mos later. All residents completed a survey
      regarding self-confidence in MSKE skills pre- and posttest teaching sessions.
      Performance of MSKE skills (based on PASSOR guidelines) and application of ACGME
      core competencies (medical knowledge, professionalism, interpersonal skills) were
      measured, and a survey was administered regarding self-confidence in MSKE skills.
      RESULTS: Posttest results showed a significant improvement of MSKE skills among
      juniors in the shoulder, lumbar spine, and knee examinations (P < 0.008), with
      the most robust improvement in the shoulder exam (P < 0.0001). Self-confidence of
      juniors in their MSKE skills increased significantly (P < 0.005). There was
      significant improvement (P < 0.008) in self-confidence in the MSKE skills of
      seniors who served as models and evaluators, but not in those who only attended
      the instructional session (P = 0.06). CONCLUSIONS: This evaluation and
      instructional method resulted in a significant improvement of MSKE skills of
      junior residents on formal testing. Using senior residents as evaluators and
      models improved their confidence in their own MSKE skills.

PMID- 18049140
TI  - Pedicle stress reaction in a teenage baseball pitcher.

PMID- 18049141
TI  - Coping with ethical dilemmas in the NICU.

PMID- 18049148
TI  - Implementation and evaluation of a best practice initiative. Venipuncture in the
      well baby.
AB  - Venipuncture is now the standard method of phlebotomy for well newborn infants at
      Kingston General Hospital (KGH), Canada. Newborn infants require at least one
      blood sample for mandatory genetic screening. Some will require additional
      samples for monitoring of hyperbilirubinemia or other laboratory tests. A change
      from capillary heel sticks to venipuncture was implemented when the lancets in
      use were discontinued and a suitable replacement could not be found at the time.
      A review of the literature discovered a Cochrane Neonatal Review that supported
      newborn venipuncture as a safe, pain-reducing practice when performed by trained
      phlebotomists. As a result, a quality improvement project was developed to
      implement the practice of venipuncture for the well newborn. The implementation
      and evaluation included lectures, demonstrations, return demonstrations, and
      eventual integration into clinical practice. Process and summative evaluation
      demonstrated a willingness of staff to learn a new procedure, particularly when
      they had identified the need for change. In addition, infants were not subjected
      to multiple, ineffective blood draws.

PMID- 18049149
TI  - Literature review. Outcomes associated with postnatal exposure to polychlorinated
      biphenyls (PCBs) via breast milk.
AB  - Forty years ago manufacturers commonly used polychlorinated biphenyls (PCBs) in a
      wide variety of products. In the late 1970s, following research demonstrating
      neurotoxicity in animals, even at low levels, PCBs were banned internationally.
      Today PCBs are widespread environmental contaminants and may be isolated from
      breast milk of women worldwide. This article provides an overview of the current
      research on the relationship between PCBs in breast milk and their effects on
      breastfed children with regard to neurological effects, growth and maturity,
      potential mitigating effects of breastfeeding, and immunologic effects. The vast
      majority of results from this body of research indicate that despite higher PCB
      loads, breastfed children continue to fare better than their formula-fed peers.
      At this point, there is no evidence of a threshold among the general population
      beyond which the risks of breastfeeding outweigh the benefits, nor is there any
      evidence demonstrating a clinically significant negative effect of postnatal
      exposure to PCBs via breast milk. To date the majority of studies conclude that
      despite substantially higher PCB loads among breastfed infants, breastfeeding is
      still preferable to formula feeding.

PMID- 18049150
TI  - A case report of a premature infant with coxsackie B1 meningitis.
AB  - This case report describes a 36-week gestational age infant diagnosed with
      coxsackie B1 meningitis at 20 days of age. A head ultrasound 5 days after
      diagnosis was consistent with cystic periventricular leukomalacia. The scientific
      literature does not clearly elucidate differences between bacterial and viral
      infections in infants. When difficulties arise, it is pertinent to consider a
      viral etiology for the underlying illness and obtain a detailed maternal and
      infant history focusing on clinical symptoms, seasonality, geographic location,
      exposure, and incubation period. Polymerase chain reaction is a rapid and
      sensitive diagnostic test for the identification of enteroviruses in
      cerebrospinal fluid, blood, urine, and throat specimens and should be performed
      as part of the general workup in the evaluation of a febrile infant with sepsis.
      In retrospect, it may have established an earlier diagnosis of meningitis,
      consequently preventing the unnecessary use of antibiotics, potentially
      decreasing the length of hospitalization, and eliminating the need for more
      detailed investigations to rule out other etiological factors. In addition,
      treatment with pleconaril may have affected the severity of the encephalitis.
      This article reviews the pathogenesis, clinical manifestations, and differential
      diagnoses of enteroviral infections, specifically focusing on the prevention,
      treatment, and prognosis of the disease and the implications for clinical
      practice.

PMID- 18049151
TI  - The ABCs of CMV.
AB  - Most infants exposed to cytomegalovirus (CMV) in utero will not be symptomatic;
      however, infants born with symptomatic CMV will have more severe consequences and
      poorer prognosis than will asymptomatic infants. The timing of infection during
      pregnancy largely affects the expected outcomes and consequences to the fetus. It
      is possible for a fetus to acquire congenital CMV infection from a nonprimary
      infection, although this accounts for a small number of cases. The presence of
      microcephaly, intrauterine growth restriction, petechiae, encephalitis,
      hepatosplenomegaly, and deafness are some of the physical characteristics of a
      congenital CMV infection. Treatment options remain limited at this time, so no
      routine screening has been recommended. The need for a vaccine or preventative
      treatment has been identified as a priority in the United States.

PMID- 18049153
TI  - Recorded maternal voice for preterm neonates undergoing heel lance.
AB  - PURPOSE: To determine if a recording of a mother's voice talking soothingly to
      her baby is useful in diminishing pain in newborns born between 32 and 36 weeks'
      gestational age (GA) during routine painful procedures. BACKGROUND: While
      maternal skin-to-skin contact has been proven efficacious for diminishing
      procedural pain in both full-term and preterm neonates, it is often not possible
      for mothers to be present during a painful procedure. Because auditory
      development occurs before the third trimester of gestation, it was hypothesized
      that maternal voice could substitute for maternal presence and be effective in
      diminishing pain response. SUBJECTS: Preterm infants between 32 and 36 weeks' GA
      (n = 20) in the first 10 days of life admitted to 2 urban university-affiliated
      neonatal intensive care units. DESIGN AND METHODS: Crossover design with random
      ordering of condition. Following informed consent, an audio recording of the
      mother talking soothingly to her baby was filtered to simulate the mother's voice
      traveling through amniotic fluid. A final 10-minute recording of repetition of
      mothers' talking was recorded with maximum peaks of 70 decibels (dB) and played
      at levels ranging between 60 and 70 ambient decibels (dbA), selected above
      recommendations of the American Academy of Pediatrics in order to be heard over
      high ambient noise in the settings. This was played to her infant by a portable
      cassette tape player 3 times daily during a 48-hour period after feedings
      (gavage, bottle, or breast). At the end of 48 hours when blood work was required
      for clinical purposes, using a crossover design, the infant underwent the heel
      lancing with or without the recording being played. The order of condition was
      randomized, and the second condition was within 10 days. The Premature Infant
      Pain Profile (PIPP) was used as primary outcome. This is a composite measure
      using heart rate, oxygen saturation, 3 facial actions, behavioral state, and
      gestational age. This measure has demonstrated reliability and validity indexes.
      RESULTS: There were no significant differences between groups on the PIPP or any
      of the individual components of the PIPP except a lower oxygen saturation level
      in the voice condition following the procedure. The second condition, regardless
      of whether it was voice or control, had higher heart rate scores and lower oxygen
      saturation scores even in the prelance baseline and warming phases. Order did not
      affect PIPP scores or facial actions. CONCLUSIONS: Different modalities of
      maternal presence would appear to be necessary to blunt pain response in infants,
      and recorded maternal voice alone is not sufficient. The loudness of the
      recording may have obliterated the infant's ability to discern the mother's voice
      and may even have been aversive, reflected in decreased oxygen saturation levels
      in the voice condition. Preterm neonates of 32 to 36 weeks' gestation may become
      sensitized to painful experiences and show anticipatory physiological response.

PMID- 18049154
TI  - NANN Position Statement 3015. NICU Nurse Involvement in Ethical Decisions
      (Treatment of Critically Ill Newborns).

PMID- 18049155
TI  - Commentary on NANN Position Statement 3015. NICU Nurse Involvement in Ethical
      Decisions (Treatment of Critically Ill Newborns).

PMID- 18049157
TI  - Cancer risk in Barrett's oesophagus.
AB  - (Table is included in full-text article.)Barrett's oesophagus results from the
      replacement of the normal squamous lining of the oesophagus by a columnar
      epithelium. It is the sole known premalignant condition for oesophageal
      adenocarcinoma. The annual cancer incidence of 1% in Barrett's oesophagus,
      calculated from published series, has been recently considered an overestimation
      owing to publication bias, and a 0.5% risk was proposed. The prerequisite of the
      presence of intestinal metaplasia for the diagnosis of Barrett's oesophagus,
      although widely accepted, is questioned by some authors. How adenocarcinoma
      incidence is influenced by requiring or not intestinal metaplasia for Barrett's
      oesophagus diagnosis is unknown. Most of the published studies included only (or
      preferentially) patients with long segments. Data on adenocarcinoma incidence in
      short segments (<3 cm) are very scarce, but it is believed to be lower than in
      long segments. The magnitude of cancer risk influences cost effectiveness of
      surveillance of Barrett's oesophagus. Frequently, therapeutic intervention is
      performed when high-grade dysplasia is diagnosed, preventing progression to
      adenocarcinoma. This could lead to an underestimation of cancer risk in Barrett's
      surveillance studies.

PMID- 18049158
TI  - Liver transplantation for nonsteroidal anti-inflammatory drug-induced liver
      failure: nimesulide as the first implicated compound.
AB  - Among industrialized countries, the rate of drug-induced liver failure varies
      widely accounting for about 1-12% of the indications for liver transplantation.
      Nonsteroidal anti-inflammatory drugs (NSAIDs) are with antibiotics the most
      frequently involved compounds. In this single-center series of 57 consecutive
      cases of acute liver failure treated by orthotopic liver transplantation, five
      were related to NSAIDs-induced liver damage, three being due to nimesulide use.
      This has to be taken as a further warning about the potential for this compound
      to induce liver failure.

PMID- 18049159
TI  - Anti-hepatitis A virus seroprevalence among patients with chronic viral liver
      disease in Korea.
AB  - BACKGROUND/OBJECTIVE: It is generally recommended that patients with chronic
      viral hepatitis should be vaccinated against hepatitis A virus (HAV) infection.
      We intended to evaluate the prevalence of IgG anti-HAV according to age in
      patients chronically infected with hepatitis B virus or hepatitis C virus in
      Korea. METHODS: From June to October 2006, 303 patients (226 male, 77 female)
      with chronic hepatitis, liver cirrhosis, or hepatocellular carcinoma were
      recruited (mean age 50.8+/-14.4 years; range 16-84). The sera were tested for
      antibodies to HAV, and overall and age-specific seroprevalence of anti-HAV was
      assessed. RESULTS: Hepatitis B virus infection was the etiology of liver diseases
      in 267 patients (88.1%), with hepatitis C virus infection in 36 (11.9%). The
      distribution of clinical diagnosis was chronic hepatitis in 86 patients (28.4%),
      liver cirrhosis in 36 (11.9%), and hepatocellular carcinoma in 181 (57.9%). The
      patients were categorized by decade of age and the distribution was as follows:
      nine patients (2.5%) in their teens, 23 (6.2%) in their 20s, 36 (12.4%) in their
      30s, 78 (25.7%) in their 40s, 72 (24.1%) in their 50s, and 85 (29%) >or=61 years.
      The overall seroprevalence of anti-HAV was 87.8% (266/303), and no difference was
      observed in sex (86.7 vs. 90.9%, P=0.42). The seroprevalence in each age group
      was 22.2, 26.1, 72.2, 97.4, 100 and 98.8%, respectively, showing marked increase
      in those over 40 years of age (P<0.001). CONCLUSION: Our study demonstrates that
      most Korean patients over 40 years of age with chronic liver disease have already
      been exposed to HAV.

PMID- 18049160
TI  - Response to antiviral therapy and hepatic expression of cyclooxygenases in
      chronic hepatitis C.
AB  - OBJECTIVES: The aims of this study were to investigate the expression of
      cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) in chronic hepatitis C
      (CHC) by immunohistochemistry, based on the hypothesis that COXs expression could
      vary according to genotype, viral load, liver steatosis, BMI and response to
      therapy and to determine whether the addition of selective COX inhibitors could
      have a rationale in increasing the efficacy of antiviral therapy. METHODS: We
      used 35 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle
      biopsy from patients with CHC (17F/18M) with one of two types of genotype (1b and
      3a). The presence of COX-1 and COX-2 in the cytoplasm of hepatocytes was scored
      on the basis of: (i) maximum intensity; (ii) dominant intensity; and (iii)
      extent. RESULTS: No significant differences were found in COX-1 and COX-2
      expression in CHC patients divided according to genotype or according to the type
      of response to combination therapy with pegylated-interferon and ribavirin. The
      only significant correlations were observed between the dominant intensity of COX
      2 and the presence of histological steatosis (P<0.01) and an inverse correlation
      between COX-2 extent and the viral load (P<0.02). CONCLUSIONS: The lack of
      correlation between COXs tissue expression and response to antiviral treatment
      suggests that there is no rationale to adding selective COX inhibitors to
      increase the efficacy of antiviral therapy, although further studies on larger
      patient populations are needed. On the contrary, there is a potential application
      for their use in the prevention and treatment of liver steatosis.

PMID- 18049161
TI  - Postmarketing hepatic adverse event experience with PEGylated/non-PEGylated
      drugs: a disproportionality analysis.
AB  - OBJECTIVE: To compare reporting frequencies of hepatic adverse events between
      PEGylated and non-PEGylated formulations of active medicinal compounds in
      spontaneous reporting systems using a data mining algorithm (DMA). METHODS:
      Statistical DMAs are being promoted as a means of identifying drug-event
      combinations that are disproportionately reported in large spontaneous reporting
      systems databases, a critical data source for pharmacovigilance. After a review
      of case reports of hepatotoxicity with PEGylated drugs possibly associated with
      the polyethylene glycol moiety, we carried out a retrospective disproportionality
      analysis of WHO's multinational drug safety database for events related to
      hepatic dysfunction comparing PEGylated versus non-PEGylated formulations of four
      active moieties. A threshold of posterior interval (PI) 95% lower limit >0 was
      used to define a signal of disproportionate reporting with a drug and an event
      and 90% PIs of the information component were compared to identify statistical
      differences between the two compounds. RESULTS: On the basis of a total of 18 477
      cases containing at least one of the drug pairs, we found disproportionate
      reporting for hepatic-related events with both PEGylated and non-PEGylated
      formulations. Overlapping of 90% PIs of the information components, however,
      suggested that there was no statistically significant difference between the
      frequency of hepatic injury reported with PEGylated versus non-PEGylated drug
      formulations. CONCLUSION: We did not find significant indicators of differential
      reporting of hepatic injury between PEGylated and non-PEGylated drug formulations
      in this exploratory analysis using one DMA. The analysis also suggests that
      comparative disproportionality methodology although not in itself determinative,
      could be one useful component of a risk management plan for monitoring the
      postmarketing experience of drug delivery systems that uses multiple methods and
      data streams.

PMID- 18049162
TI  - Gradual improvement of liver function after administration of ursodeoxycholic
      acid in an infant with a novel ABCB11 gene mutation with phenotypic continuum
      between BRIC2 and PFIC2.
AB  - OBJECT: The authors report the case of a boy with PFIC type 2 or BRIC type 2 who
      suffered from liver dysfunction at 2 months after birth. METHODS AND RESULTS: A
      liver biopsy specimen revealed mild liver cirrhosis, and the findings resembled
      those observed in Byler disease. Genetic examination revealed a normal familial
      intrahepatic cholestasis-1 gene, but a heterozygous mutation for the ABCB11,
      C1620A (F540L), was observed. Therefore, the patient was initially diagnosed with
      PFIC type 2. For 3 years after the diagnosis, he had severe pruritus, an
      increased serum bile acid, and normal serum values of gamma-glutamyl
      transaminase. At the age of 2, treatment with administration of ursodeoxycholic
      acid was started; subsequently, a gradual improvement in his liver function was
      observed. At the age of 3, he suffered from massive intestinal and pulmonary
      hemorrhage, which improved immediately after the administration of vitamin K. He
      was then admitted to our hospital for liver transplantation. At 1 month after the
      admission, his liver dysfunction showed further improvement, except for a mild
      increase in the serum bile acid level. This condition did not show any change
      during the 5-year follow-up period. In addition, the patient showed severe growth
      failure and was diagnosed with growth hormone deficiency. Hence, he receives
      growth hormone administration. CONCLUSION: The patient could be genetically
      diagnosed with bile salt export pump disease of PFIC type 2 or BRIC type 2.
      Various clinical features are observed in PFIC or BRIC patients with ABCB11
      mutation.

PMID- 18049163
TI  - Association of CTLA4 single nucleotide polymorphisms with viral but not
      autoimmune liver disease.
AB  - BACKGROUND: CTLA4 is an inhibitory receptor expressed on a subset of T
      lymphocytes. Single nucleotide polymorphisms of the CTLA4 gene have been
      implicated in autoimmune diseases, including autoimmune hepatitis and primary
      biliary cirrhosis. In reverse form, CTLA4 variations are associated with chronic
      infections such as chronic hepatitis B. METHODS: CTLA4 variations -318C>T and
      +49A>G were analyzed in 2366 patients with chronic liver disease of various
      etiologies, including 323 patients with chronic hepatitis B virus (HBV)
      infection, 1181 patients with chronic hepatitis C virus infection, 180 patients
      with primary biliary cirrhosis, and 127 patients with autoimmune hepatitis, as
      well as 202 healthy control individuals. Genotyping was performed by melting
      curve analysis. RESULTS: The -318C>T variation was underrepresented in patients
      with chronic HBV infection compared with healthy controls (14.6 vs. 25.7%,
      P=0.002) and with patients with chronic liver disease of other origin (14.6 vs.
      20.7%, P=0.011). Patients with cryptogenic cirrhosis also showed a lower
      frequency of the -318T allele than healthy controls (12.0 vs. 25.7%, P=0.014). No
      association of the +49G>A variation was found with any diagnosis, including
      autoimmune hepatitis and primary biliary cirrhosis. CONCLUSION: We describe the
      association of the CTLA4 -318C>T variation with chronic HBV infection and
      cryptogenic cirrhosis but find no association of the +49G>A variation with
      autoimmune liver disease.

PMID- 18049164
TI  - DNA methyltransferase 1 knockdown induces silenced CDH1 gene reexpression by
      demethylation of methylated CpG in hepatocellular carcinoma cell line SMMC-7721.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common causes of
      cancer-related mortality in the world; however, the molecular mechanisms leading
      to hepatocyte transformation, especially in epigenetic mechanisms (such as DNA
      methylation) are still poorly understood. DNA methyltransferase 1 (DNMT1) is the
      predominant maintenance methyltransferase gene required to maintain DNA
      methylation patterns in mammalian cells. AIM AND METHODS: To explore the role of
      DNMT1 in the regulation of expression of tumor-related genes in human HCC cells
      via DNA methylation of the regulatory CpG islands, we stably transfected
      expression constructs containing small interfering RNA (siRNA) of DNMT1 into the
      human HCC cell line, SMMC-7721. RESULTS: RNA interference knocked down specific
      DNMT1 protein expression, resulting in the demethylated promoter of CDH1 and the
      reexpression of CDH1 in 7721-pMT1. By contrast, promoter methylation and lack of
      gene expression were maintained when the cell lines had control constructs. Knock
      down of DNMT1 expression by siRNA induced the promoter of CDH1 demethylation and
      upregulated CDH1 transcription. High-density oligonucleotide gene expression
      microarrays were used to examine the effects of DNMT1 knock down on human HCC
      cells (SMMC-7721); these showed that a number of genes were induced in the DNMT1
      knock down cell lines, including some important tumor-related genes such as
      PDCD4, DCN and PTGES except CDH1. Only approximately 78% of the induced genes
      have CpG islands within their 5' regions, suggesting that certain genes activated
      by DNMT1 siRNA might not have resulted from the direct inhibition of promoter
      methylation. CONCLUSION: In hepatocellular carcinoma, DNMT1 is necessary to
      maintain the methylation of CpG islands in certain tumor-related genes.

PMID- 18049165
TI  - Analysis of apoptosis and cell proliferation after high intensity-focused
      ultrasound ablation combined with microbubbles in rabbit livers.
AB  - OBJECTIVE: To analyze apoptosis and expression of proliferating cell nuclear
      antigen (PCNA) sequentially in the rabbit liver tissue after high-intensity
      focused ultrasound (HIFU) ablation combined with microbubbles. METHODS: Fifty
      rabbits were divided into two groups randomly. Rabbits in group I received
      injections with ultrasound contrast agent Sonovue, before HIFU ablation, on their
      livers and those in group II were ablated by a single HIFU exposure without
      microbubbles. Rabbits were killed on days 0, 1, 3, 7 and 14 after HIFU ablation.
      The livers were excised for light microscopic examination with hematoxylin and
      eosin staining, immunohistochemical staining for PCNA expression and terminal
      deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling (TUNEL)
      staining for apoptosis. RESULTS: A fibra tissue band composed of fibrocytes and
      capillary vessels, which was detected by light microscope in the rim of the
      targeted area after 3 days in group I, was wider than that in group II. The
      apoptosis index (the number of apoptotic events divided by the total cell number
      in the same field) and PCNA-positive index (the number of PCNA-positive cells
      divided by the total cell number in the same field) in group I on days 0, 1, 3, 7
      and14 after HIFU ablation were higher than those in group II. CONCLUSION:
      Microbubbles can improve the apoptosis and cell proliferation in zones
      surrounding coagulated necrosis areas after HIFU ablation, which may be explored
      to benefit enhanced HIFU treatment.

PMID- 18049166
TI  - Short segment columnar-lined oesophagus: an underestimated cancer risk? A large
      cohort study of the relationship between Barrett's columnar-lined oesophagus
      segment length and adenocarcinoma risk.
AB  - OBJECTIVE: Longer columnar-lined oesophagus (CLO) segments have been associated
      with higher cancer risk, but few studies have demonstrated a significant
      difference in neoplastic risk stratified by CLO segment length. This study
      establishes adenocarcinoma risk in CLO by segment length. METHODS: This is a
      multicentre retrospective observational study. Medical records of 1000 patients
      registered from six centres were examined and data extracted on demographic
      factors, endoscopic features and histopathology of oesophageal biopsies.
      Adenocarcinoma incidence was evaluated for patients stratified by their
      diagnostic segment length. RESULTS: Seven hundred and eighty-one patients had
      biopsy-proven CLO and a segment length recorded. Four hundred and ninety patients
      had at least 1 year of follow-up, providing 2620 patient-years of follow-up for
      incidence analysis. The overall annual adenocarcinoma incidence was 0.62%/year
      (95% confidence interval: 0.36-1.01). The annual incidence in the segment length
      groups was 0.59% (0.19-1.37) in short segment (<or=3 cm), 0.099% (0.025-0.55) in
      >3 <or=6 cm, 0.98% (0.27-2.52) in >6 <or=9 cm and 2.0% (0.73-4.35) in >9 cm;
      P=0.004. CONCLUSION: This study demonstrates that the neoplastic risk of CLO
      varies according to segment length, and that overall, the risk of adenocarcinoma
      development is similar in short-segment and long-segment (>3 cm) CLO. The highest
      adenocarcinoma risk was found in the longest CLO segments and lowest risk in
      segments >3 <or=6 cm.

PMID- 18049167
TI  - Angiotensin-converting enzyme insertion/deletion gene polymorphism in
      inflammatory bowel diseases.
AB  - INTRODUCTION: The renin-angiotensin system is strictly related to the kallikrein
      kinin system and both are involved in many physiological and disease conditions
      and possibly in the pathogenesis of inflammatory bowel disease (IBD). Angiotensin
      converting enzyme (ACE) is the pivotal enzyme of the renin-angiotensin system and
      the main catabolic enzyme of the kallikrein-kinin system. The ACE I/D
      (insertion/deletion) is a polymorphism of the gene encoding for ACE: participants
      who are homozygous for the D allele exhibit higher ACE levels, which in turn
      appear to play a deleterious role in several diseases. AIM: To study the
      prevalence of ACE I/D polymorphism in IBD patients and its possible association
      with disease features. METHODS: A total of 232 IBD patients, 124 with ulcerative
      colitis (UC) and 108 with Crohn's disease and 99 healthy controls were genotyped
      for the ACE I/D polymorphism. RESULTS: DD, ID and II genotypes distribution did
      not show significant differences between IBD patients and controls: 42.2 vs.
      40.4%, 42.7 vs. 47.5% and 15.1 vs. 12.1%, respectively. No significant difference
      was observed between Crohn's disease and UC patients. Within UC patients, the
      presence of DD genotype and the carriage of the D allele were significantly
      associated with the presence of extraintestinal manifestations: odds ratio (OR)
      4.08, 95% confidence interval (CI): 1.62-10.28; P<0.003 and OR=3.07, 95% CI: 1.45
      6.48; P<0.003, respectively. No significant association was found with other IBD
      clinical features. CONCLUSIONS: The ACE I/D polymorphism is not associated with
      IBDs but the D allele appears to increase the risk of developing extraintestinal
      manifestations in UC patients.

PMID- 18049168
TI  - Prevalence of coeliac disease in the adult population of central Greece.
AB  - OBJECTIVES: Recent studies from several countries have shown that coeliac disease
      (CD) is increasingly being diagnosed in adults, as the availability of new,
      accurate serologic tests has made screening in the general population possible.
      No data exist regarding the prevalence of CD in Greece. The aim of this study was
      the implementation of a serologic screening procedure for CD in the adult general
      population of Thessaly, an area of central Greece, using a novel diagnostic
      algorithm. METHODS: The study included 2230 participants (1226 women, 1004 men,
      median age 46 years, range 18-80 years), selected by systematic random sampling,
      from the adult general population of Thessaly. All the serum samples were tested
      for total immunoglobulin A (IgA)-serum levels, to exclude IgA deficiency. Samples
      with total IgA within the normal range were tested for IgA antibodies against
      native human-tissue transglutaminase (anti-tTG); samples that were anti-tTG
      positive were tested for IgA antiendomysial antibodies (EmA). Samples from
      participants with selective IgA deficiency were examined for IgG antigliadin
      antibodies. Participants who were EmA-positive or antigliadin antibody-positive
      were referred for intestinal biopsy and human leucocyte antigen (HLA) typing.
      RESULTS: No participant with selective IgA deficiency was detected. Four
      individuals tested positive for EmA, all of whom were biopsy-proven coeliacs.
      Therefore, the CD prevalence in this general population sample is 1 : 558 or 1.8
      per 1000 (SE 0.13). The four new patients with abnormal histology (two men, two
      women) were aged between 18 and 35 years. Two of them were considered to be
      asymptomatic and two presented with a subclinical course. All four had the
      heterodimer HLA-DQ2. CONCLUSIONS: This first serological screening study for CD
      in Greece has demonstrated that CD prevalence in Thessaly is among the lowest
      reported in Europe.

PMID- 18049169
TI  - Chemotherapy-induced suppression to adenoma or complete suppression of the
      primary in patients with stage IV colorectal cancer: report of four cases.
AB  - BACKGROUND: Although modern chemotherapy of stage IV advanced colorectal cancer
      (CRC) has impressively improved overall survival, the response of the primary
      tumor has not been studied because surgical resection of the primary continues to
      be the standard procedure in stage IV CRC. AIM: Long-term follow-up of the
      primary in patients with stage IV CRC under chemotherapy. METHODS AND RESULTS:
      Here we report on the histological changes in the primary tumor in four patients
      suffering from stage IV CRC. Systemic chemotherapy was started immediately after
      endoscopic tumor debulking in three cases. In one case no endoscopic intervention
      was performed before chemotherapy. Neither macroscopic nor histological evidence
      for malignant tumor growth was found at the former site of the primary after 6,
      23, 26 or 48 months, respectively. Two patients had a complete suppression of the
      primary, two patients had an adenoma at the former site of the primary. To date,
      three patients have died because of progression of liver metastases and one
      patient is still alive with no signs of tumor growth. CONCLUSION: The four cases
      illustrate that today's chemotherapy may effectively induces suppression of the
      primary in CRC. The development of CRC may follow different pathways.

PMID- 18049170
TI  - Adjuvant chemotherapy for stage II colon cancer: influence of care structures'
      characteristics on a controversial clinical practice.
AB  - BACKGROUND: Adjuvant chemotherapy for stage II colon cancer is a controversial
      practice and is not recommended by the French Consensus Conference outside of
      therapeutic trial. OBJECTIVE: To assess, within a well-defined population, the
      influence of hospital characteristics in this practice. PATIENTS AND METHODS: In
      the Rhone-Alpes region (10% of the French population), 534 patients presenting
      with colon cancer stage II were operated on in 81 hospitals in the year 2000. The
      influence of hospital characteristics on the use of adjuvant chemotherapy was
      assessed using a multivariate logistic regression. RESULTS: Overall, 19.5% of
      patients received adjuvant chemotherapy. Younger age, T4 tumour, hospital volume
      lower than 20 colon cancer surgeries [odds ratio (OR) 2.96; P<0.001], formal
      multidisciplinary input with specific written account (OR 3.25; P=0.001), private
      funding of the hospital (OR 1.82; P=0.019), and clinical complications at
      diagnosis were independently associated with higher rates of chemotherapy. On the
      other hand, a number of examined lymph nodes lower than recommendations did not
      have any influence on chemotherapy use. CONCLUSION: Hospital characteristics had
      independently influenced the practice of adjuvant chemotherapy in stage II colon
      cancer. The more important institutional factor was the hospital procedure
      volume. The decisions of the multidisciplinary committees appeared at times
      paradoxical; a more comprehensive evaluation of this practice is needed.

PMID- 18049171
TI  - Conscious sedation during endoscopic retrograde cholangiopancreatography:
      midazolam or midazolam plus meperidine?
AB  - BACKGROUND AND OBJECTIVE: No consensus exists for the safest and most effective
      agent and for optimal drug doses for sedation during endoscopic retrograde
      cholangiopancreatography (ERCP). We aimed to compare the efficacy of midazolam
      with that of midazolam+meperidine, which provided comfort for the patient during
      ERCP. MATERIALS AND METHODS: The patients were randomized to sedation with
      midazolam only (2.87+/-0.67 mg) (n=48, median age 55.54+/-14.66, 21 women, 27
      men) or midazolam (1.82+/-0.71 mg) with meperidine (42.81+/-14.61 mg) (n= 48,
      median age 55.48+/-2.57, 20 women, 28 men). Procedure-related parameters and the
      efficacy of sedation as assessed by the endoscopist and the patients were
      compared. RESULTS: Prior endoscopic history, preprocedure anxiety scores, age,
      sex, baseline vital signs and type of interventions were similar in both groups.
      Sedation level, duration of procedure and recovery time were comparable in both
      groups. Sedation quality assessment scale was significantly higher in the
      midazolam with meperidine group. Degree of pain sensed during the procedure was
      significantly lower in the midazolam with meperidine group. Midazolam with
      meperidine group had better patient satisfaction. Twenty-four hours after the
      procedure, the degree of amnesia between both sedation groups was similar. The
      number of patients unwilling to repeat the procedure was distinctly higher in
      midazolam group. Development of hypoxia and arrythmia in the midazolam and
      midazolam with meperidine groups were comparable. Two patients in the midazolam
      group developed paradoxical agitation. CONCLUSIONS: Conscious sedation for ERCP
      can be successfully and safely achieved by using either only midazolam or a low
      dose of midazolam with meperidine. Adding of meperidine to midazolam resulted in
      better patient and endoscopist comfort.

PMID- 18049172
TI  - Suspected choledocholithiasis: endoscopic ultrasound or magnetic resonance
      cholangio-pancreatography? A systematic review.
AB  - There is a lack of consensus on the optimal noninvasive strategy for patients
      with suspected choledocholithiasis after a negative transabdominal ultrasound
      and/or computed tomography. A meta-analysis was conducted to compare the
      diagnostic ability of endoscopic ultrasound (EUS) and magnetic resonance
      cholangio-pancreatography (MRCP) in patients with suspected common bile duct
      (CBD) stones. A search, using the following terms 'MRCP', 'EUS' and
      'Choledocholithiasis' in Pubmed and Cochrane Controlled Trials Register, was
      performed. Abstract books and reference list of review articles, as well as
      relevant studies, were also searched to complete our EUS versus MRCP for
      choledocholithiasis comparison studies database. The analysis demonstrated that,
      with respect to sensitivity, specificity and accuracy, there was no statistically
      significant difference between EUS and MRCP for the detection of
      choledocholithiasis. Our meta-analysis of prospective comparison of MRCP and EUS
      for the detection of choledocholithiasis yielded statistically similar diagnostic
      values for both techniques.

PMID- 18049173
TI  - Acute hepatitis E with severe jaundice: report of three cases.
AB  - Hepatitis E virus (HEV) is the main cause of enterically transmitted non-A
      hepatitis worldwide. Infection is endemic in developing countries. Disease course
      is benign, and severe jaundice is rarely reported. Three patients presented to
      our department with symptomatic acute hepatitis. Two of them had recently
      travelled to endemic areas. Jaundice was very marked in all patients. HEV
      infection was documented by HEV antibodies and by HEV-RNA detection in serum and
      stools. In the autochthonous case, immunoglobulin-M was absent, and diagnosis was
      established on HEV-RNA amplification by real-time reverse transcriptase-PCR.
      Comprehensive investigation for concomitant causes of liver disease was negative
      in all patients. Histological features showed marked cholestasis with multiple
      bile plugs in dilated canaliculi. In conclusion, acute hepatitis E may be
      autochthonous in developed countries and patients may present with severe
      jaundice. HEV-RNA detection by real-time reverse transcriptase-PCR is a very
      efficacious diagnostic tool in anti-HEV immunoglobulin-M-negative cases.

PMID- 18049174
TI  - Inflammatory pseudotumor of the liver successfully treated with nonsteroidal anti
      inflammatory drugs: a challenge diagnosis for one not so rare entity.
AB  - Inflammatory pseudotumor of the liver is a rare, benign lesion characterized by a
      well-circumscribed mass of chronic inflammatory cell infiltration and
      proliferating fibrous tissue. Its etiology remains unclear, although inflammatory
      processes have been proposed. It is often misdiagnosed as a malignant tumor, and
      the management has been traditionally surgical. We report the case of a 16-year
      old boy who was referred from another hospital with a fever of >38 degrees C with
      rigor and right upper quadrant pain which he had suffered from for 5 days. The
      ultrasonographic computed tomography and MRI findings were not diagnostic, and we
      performed a needle biopsy from the lesion that was consistent with inflammatory
      pseudotumor (of liver, mixed fibrous tissue and chronic inflammatory cell
      infiltration). The patient was treated with nonsteroidal anti-inflammatory drugs
      and had an uneventful clinical course. During follow-up, the lesion subsequently
      shrank to completely vanish 1 year later.

PMID- 18049175
TI  - Type 1 and 2 gastric carcinoid tumors: long-term follow-up of the efficacy of
      treatment with a slow-release somatostatin analogue.
AB  - Little is known about the long-term results of treating gastric carcinoid tumors
      with a slow-release somatostatin analogue. We report three patients with type 1
      and 2 gastric carcinoid tumors who were treated in the above mentioned way and
      followed for 27-50 months. In all cases, alternative endoscopic or surgical
      management was considered but deemed inappropriate. Treatment with a slow-release
      somatostatin analogue was begun in light of a favorable recent report. The result
      was regression or complete disappearance of macroscopic fundal tumors. No side
      effects were reported and, most notably, none of the patients developed
      gallstones. This small study may help define the optimal duration, dose, and
      administration interval of the treatment. Slow-release somatostatin analogue is a
      safe and efficacious treatment for type 1 and 2 gastric carcinoid tumors, and can
      be used when tumors are growing rapidly. Slow-release somatostatin analogue
      represents an alternative to repeated endoscopic treatment or high-risk surgery.

PMID- 18049176
TI  - Cystic lymphangioma of the mesentery and hyposplenism in celiac disease.
AB  - Celiac disease is characterized by intestinal inflammation and mucosal atrophy
      that improves on a gluten-free diet. Delayed diagnosis can result in diet
      refractory disease known as refractory sprue, which is linked to other disorders
      (intestinal lymphoma, ulcerative jejunoileitis, mesenteric lymph-node cavitation,
      collagenous sprue, malignancy) and carries a poor prognosis. Here we report the
      case of a young woman diagnosed with Marsh stage 3C celiac disease with
      intestinal occlusion due to intra-abdominal cystic lymphangioma mimicking
      mesenteric lymph-node cavitation, and hyposplenism. Despite a number of
      prognostically negative features, the disease has been managed successfully for
      the past 2 years with a gluten-free diet. The pathogenesis, prognosis and
      therapeutic implications are discussed.

PMID- 18049177
TI  - Clinical pattern of elderly cirrhosis: an Indian experience.

PMID- 18049178
TI  - Critical flicker test: yet another tool for minimal hepatic encephalopathy.

PMID- 18049179
TI  - The Millennium Development Goals: a challenge to epidemiologists.

PMID- 18049180
TI  - Why epidemiologists cannot afford to ignore poverty.
AB  - Epidemiologists cannot afford to ignore poverty. To do so would, first, wrongly
      obscure the devastating impact of poverty on population health, and, second,
      undercut our commitment to scientific rigor. At issue is doing correct science,
      not "politically correct" science. Blot poverty and inequity from view, and not
      only will we contribute to making suffering invisible but our understanding of
      disease etiology and distribution will be marred. To make this case, I address
      current debates about the causal relationships between poverty and health, and
      provide examples of how failing to consider the impact of socioeconomic position
      has biased epidemiologic knowledge and harmed the public's health. By definition,
      the people we study are simultaneously social beings and biologic organisms-and
      we cannot study the latter without taking into account the former. It is the
      responsibility of all epidemiologists, and not only social epidemiologists, to
      keep in mind the connections between poverty and health.

PMID- 18049181
TI  - Poverty, environment, and health: the role of environmental epidemiology and
      environmental epidemiologists.
AB  - International attention is focusing increasingly on environmental concerns, from
      global warming and extreme weather to persistent chemical pollutants that affect
      our food supplies, health and well-being. These environmental exposures
      disproportionately affect the poor and those residing in developing countries,
      and may partly explain the persistent social gradients in health that exist
      within and between nations. We support recent calls for environmental
      epidemiologists to play a more active role in furthering the global agenda for
      sustainability, environmental health and equity. We further suggest that the
      discipline of environmental epidemiology, as well as relevant funding agencies,
      broaden their focus to include rigorous research on the upstream, larger-scale
      societal factors that contribute to inequitable patterns of exposure and health
      outcomes. By widening the scope of our vision and increasing the strength and
      breadth of the evidence base about how poverty and environment together affect
      health, we can better participate in efforts to promote social justice and
      responsible use and protection of the environment, and thus reduce health
      inequities. That is both a primary mode and rationale for achieving
      sustainability.

PMID- 18049182
TI  - Measuring progress towards equitable child survival: where are the
      epidemiologists?
AB  - The fourth Millennium Development Goal (MDG) is to achieve a two-thirds reduction
      in the mortality of under the age of 5 years children between 1990 and 2015. Only
      7 of the 60 priority countries are currently on track towards the goal, and
      intensified efforts are required both globally and nationally. Tackling
      inequities is essential for reaching this goal, because children from poor
      families are consistently at higher risk of dying. Efforts should be concentrated
      on achieving high and equitable coverage with low-cost, effective, off-the-shelf
      interventions, and on monitoring progress among different social groups.
      Measuring inequities in mortality, morbidity, nutritional status, and coverage,
      however, is fraught with methodologic difficulties in countries where routine
      statistics are unreliable -- a group that includes all high-mortality countries.
      Key methodologic challenges are discussed, with arguments for greater involvement
      of epidemiologists in measurement exercise that so far has been led by
      demographers, statisticians, and economists.

PMID- 18049183
TI  - Armed conflict and poverty in Central America: the convergence of epidemiology
      and human rights advocacy.
AB  - Several armed conflicts took place in Central America during the last 3 decades
      of the 20th century. In this commentary, we discuss (1) studies describing the
      interrelationships among health, violence, and poverty during and after these
      conflicts and (2) some important lessons learned from these studies. We hope that
      those lessons help epidemiologists and others who must confront, and describe,
      similar situations elsewhere.

PMID- 18049184
TI  - Depressive symptoms in low-income women in rural Mexico.
AB  - BACKGROUND: Depression is a leading cause of death and disability worldwide. This
      paper reports a cross-sectional analysis of demographic, socioeconomic, physical,
      and psychosocial factors associated with depressive symptoms among poor women in
      rural Mexico. METHODS: A cross-sectional study of 5457 women, age 20-70 years,
      were interviewed from a random sample of households from 279 poor communities
      with fewer than 2500 inhabitants in 7 rural Mexican states. Depressive symptoms
      were assessed using the Spanish translation of the Center for Epidemiologic
      Studies-Depression scale. Several other individual- and household-level variables
      were also obtained. Using hierarchical modeling, linear regression analysis, and
      population intervention model parameters, we explored correlates of depressive
      symptoms in this population. RESULTS: Most of the variation in depressive
      symptoms was at the individual level. Psychosocial factors were most strongly
      correlated with depressive symptoms; perceived stress, lack of personal control
      or social support, and low social status exhibited the strongest associations.
      Using the US-based standard Center for Epidemiologic Studies-Depression cutoff
      score of 16, 51% of this population fall into the category "at risk" for clinical
      depression; however, this cutoff may not be the most appropriate in this context.
      CONCLUSION: This sample of low-income women in rural Mexico reported a relatively
      high prevalence of depressive symptoms. The analyses suggest that reducing
      perceived stress would have the largest potential impact on depressive symptoms
      in this population. However, any interventions should take into account the broad
      context of the population's overall health. The alleviation of poverty,
      improvement of educational opportunities, and other interventions to address root
      causes of poor mental health must also be considered.

PMID- 18049185
TI  - Air pollution, social deprivation, and mortality: a multilevel cohort study.
AB  - BACKGROUND: It is becoming increasingly evident that exposure to air pollution
      and its adverse effects are not equitably distributed. Our goal was to
      investigate the role of social deprivation in explaining the effect of
      neighborhood differences in level of air pollution fine particulates (PM2.5) on
      mortality when the indicators of social deprivation are measured at both
      individual level and at neighborhood level. METHODS: All inhabitants registered
      in Oslo, Norway on 1 January 1992 in the age group 50-74 years (n = 105,359)
      constitute the study base. We used an air dispersion model (AirQUIS) to estimate
      levels of exposure in the period 1992-1995 in all 470 administrative
      neighborhoods. These data were linked to Census, educational, and death
      registries. Deaths were recorded in the period 1992-1998. MAIN RESULTS: PM2.5 was
      associated with most neighborhood-level indicators of deprivation, as was most
      clearly seen for type of dwelling and ownership of dwelling. The effect of PM2.5
      on mortality was to some extent explained by these indicators independently of
      the corresponding individual-level indicators. CONCLUSIONS: Findings from this
      study suggest that socially deprived neighborhoods have higher exposure to air
      pollution. Deprivation at both the individual and neighborhood level is
      associated with air pollution, accounting for some of the excess mortality
      associated with air pollution in these neighborhoods.

PMID- 18049186
TI  - Papanicolaou smears induce partial immunity against sexually transmitted viral
      infections.
AB  - BACKGROUND: In a case-control study of hormonal contraceptives and invasive
      cervical cancer, an unexpected finding was a substantial decline in the
      prevalence of high-risk human papillomavirus (HPV) infection according to the
      lifetime number of Pap smears received. Here we assess the risk of 3 sexually
      transmitted viral infections -- herpes simplex virus 2 (HSV2), HPV, and human
      immunodeficiency virus (HIV) 1 and 2 -- in relation to the lifetime receipt of
      Pap smears. METHODS: Stored sera taken from 1540 controls were tested for HSV2
      and HIV; cervical scrapings were tested for HPV. Confounder-adjusted odds ratios
      for the lifetime receipt of Pap smears were estimated, relative to never having
      had a Papanicolau test. RESULTS: For ever-receipt of a Papanicolau test, the odds
      ratios for HSV2 and HPV were 0.7 (95% confidence interval = 0.5-0.9) and 0.5 (0.3
      0.7), respectively, and there were dose-response trends according to the lifetime
      number of Pap smears received (test for trend P = 0.02 and 0.04, respectively).
      For HSV2 the odds ratios according to last receipt declined from 0.8 for 10 or
      more years previously to 0.4 for <1 year previously (trend P = 0.002). For HPV
      the ORs were 0.4 (0.3-0.7) for last receipt 5-9 years previously and 0.5 (0.4
      0.8) for less than 5 years previously; for HIV the odds ratio for last receipt
      less than 5 years previously was 0.4 (0.3-0.9). For HSV2 and HIV the crude odds
      ratio estimates were systematically lower than the adjusted estimates, and
      residual confounding cannot be ruled out. In particular, the true number of
      sexual partners may have been under-reported, and there was no information on the
      sexual activity of the male partners, or on other health behaviors of the women
      or their partners. CONCLUSION: We hypothesize that Pap smears may provoke a short
      term immune response against sexually transmitted viral infections.

PMID- 18049187
TI  - Breast-feeding, adipokines, and childhood obesity.
AB  - One mechanism by which breast-feeding may protect against the development of
      childhood obesity is through the activity of components of breast milk. In an
      article published in this issue of Epidemiology, Weyermann et al found that
      overweight at age 2 years was associated with higher levels of adiponectin, a
      hormone secreted by fat cells, in the breast milk of mothers who breast-fed their
      infants for at least 6 months. This finding is surprising for several reasons: it
      is doubtful that infants absorb ingested adiponectin; prior literature suggests
      that adiponectin would reduce, rather than increase, risk for overweight; and the
      authors did not find associations with breast milk leptin, another adipokine. It
      is possible that adipokine exposure in infancy determines later weight status,
      but fundamental research is needed on associations of circulating adipokines with
      excess weight gain and on determinants of adipokine levels.

PMID- 18049188
TI  - The brave new world of lives sacrificed and saved, deaths attributed and avoided.
AB  - Attributable risks are routinely estimated in "risk-factor" epidemiology. Often,
      these risks are interpreted as the numbers of deaths caused by (or numbers of
      lives lost by) exposure to the factor of interest. It is then often surmised that
      removal of exposure will avoid deaths and save lives. This reasoning leads to
      confusion because of 2 underlying assumptions. One is that removal of the
      exposure will reduce permanently the annual number of deaths by the number
      attributed to the factor. In reality, deaths are merely postponed and lives are
      merely prolonged; estimating the effect of exposure on life expectancy is both
      more straightforward and of greater public health interest. The other misleading
      premise is that the deaths attributed to a certain risk factor can be identified.
      While such identification may be possible for certain immediate external causes
      of death (eg, accidents), it is not usually feasible for deaths attributed to
      factors that merely contribute to development of chronic disease and ultimately
      death. For such exposures, it is more reasonable to suggest that they contribute
      to death in all who are exposed - more so in some people than in others. Again,
      it is more appropriate to calculate the average loss of life expectancy
      associated with exposure from follow-up studies; the years of life lost by
      individuals who are exposed then varies around this average. The "real age"
      concept popularized in lifestyle Web sites and television programs may be more
      useful than calculations of the numbers of attributable deaths for communicating
      individual as well as public health risks associated with common environmental,
      occupational and lifestyle risk factors.

PMID- 18049189
TI  - Probing STROBE.

PMID- 18049190
TI  - Is there a dark phase of this STROBE?
AB  - Suggestions for improving the reporting of observational epidemiologic studies
      are to be encouraged, but we believe the required use in reports of a checklist
      of design and analytic features relevant to study quality would have detrimental
      consequences.

PMID- 18049191
TI  - Suggestions for STROBE recommendations.
AB  - The STROBE initiative is an excellent approach to improving observational
      epidemiologic studies. Our concerns include: 1) the need for further emphasis on
      presenting a clear definition of the hypothesis, its biologic rationale, and its
      implication to the health of the public; 2) correction of the glaring omission in
      the STROBE guidelines of the necessity to consider the incubation periods for
      risk factors and diseases and to review other biologically relevant issues that
      often have a major impact on the plausibility of the observed association; 3) the
      essential importance of guidance about a careful definition of host factors,
      including a clear statement of results specific to race, sex and ethnicity rather
      than merely stating: "The interaction term was not significant"; 4) the
      importance of specifying that all studies should present the actual rates or
      numbers of events in relation to the size of the population, including the actual
      numbers for each independent variable in a multiple regression analysis, rather
      than solely presenting a hazards ratio; and 5) the need to restrict the P value
      only to those hypotheses that were generated prior to the data analysis,
      reserving retrospective analyses to point estimates and confidence limits.

PMID- 18049192
TI  - Some guidelines on guidelines: they should come with expiration dates.
AB  - The STROBE guidelines (for Strengthening the Reporting of OBservational Studies
      in Epidemiology) add to a lengthy catalog of attempts to keep epidemiologists on
      more or less straight and more or less narrow paths charted by guideline authors.
      STROBE has an ambitious goal, and may prove highly useful for some. It raises
      concern, however, about a problem generic to guidelines, namely how long they
      will be useful. Guidelines may be inevitable, but they can foster ossification
      and be counterproductive. Who today would be happy with epidemiology guidelines
      issued in, say, 1960, 1970, 1980, or even, 1990? One solution is to offer each
      set of guidelines with an expiration date, beyond which it would cease to apply.
      Such a policy would at least prompt revisions. We propose that the STROBE
      guidelines might expire on 31 December 2010 or 3 years after any revision.

PMID- 18049193
TI  - The making of STROBE.
AB  - This commentary gives a personal view of drafting the "Strengthening the
      Reporting of Observational Studies in Epidemiology" (STROBE) statement, by one of
      its authors. My initial wariness about guidelines for observational research was
      overcome by focusing on clarity of reporting, rather than on how research should
      be done. Areas of tension that arose when drafting STROBE include the problem of
      finding common ground among researchers with different research backgrounds,
      questions of the intended audience (professional epidemiologists or statisticians
      vs. all researchers who use epidemiologic study designs), and the fine line
      between encouraging clarity of reporting vs. prescribing how to do research.
      STROBE is not an instrument to evaluate the quality of research: research can be
      reported clearly or not, irrespective of its intrinsic quality. However, the
      ultimate benefit of STROBE might be that more comprehensive reporting allows for
      better discussions about published observational research, which may lead to
      better decisions about what new analyses or new studies are needed to solve a
      problem.

PMID- 18049194
TI  - The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
      statement: guidelines for reporting observational studies.
AB  - Much biomedical research is observational. The reporting of such research is
      often inadequate, which hampers the assessment of its strengths and weaknesses
      and of a study's generalizability. The Strengthening the Reporting of
      Observational Studies in Epidemiology (STROBE) Initiative developed
      recommendations on what should be included in an accurate and complete report of
      an observational study. We defined the scope of the recommendations to cover
      three main study designs: cohort, case-control and cross-sectional studies. We
      convened a 2-day workshop in September 2004, with methodologists, researchers,
      and journal editors to draft a checklist of items. This list was subsequently
      revised during several meetings of the coordinating group and in e-mail
      discussions with the larger group of STROBE contributors, taking into account
      empirical evidence and methodological considerations. The workshop and the
      subsequent iterative process of consultation and revision resulted in a checklist
      of 22 items (the STROBE Statement) that relate to the title, abstract,
      introduction, methods, results, and discussion sections of articles. 18 items are
      common to all three study designs and four are specific for cohort, case-control,
      or cross-sectional studies. A detailed "Explanation and Elaboration" document is
      published separately and is freely available on the web sites of PLoS Medicine,
      Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement
      will contribute to improving the quality of reporting of observational studies.

PMID- 18049195
TI  - Strengthening the Reporting of Observational Studies in Epidemiology (STROBE):
      explanation and elaboration.
AB  - Much medical research is observational. The reporting of observational studies is
      often of insufficient quality. Poor reporting hampers the assessment of the
      strengths and weaknesses of a study and the generalizability of its results.
      Taking into account empirical evidence and theoretical considerations, a group of
      methodologists, researchers, and editors developed the Strengthening the
      Reporting of Observational Studies in Epidemiology (STROBE) recommendations to
      improve the quality of reporting of observational studies. The STROBE Statement
      consists of a checklist of 22 items, which relate to the title, abstract,
      introduction, methods, results and discussion sections of articles. Eighteen
      items are common to cohort studies, case-control studies and cross-sectional
      studies and four are specific to each of the three study designs. The STROBE
      Statement provides guidance to authors about how to improve the reporting of
      observational studies and facilitates critical appraisal and interpretation of
      studies by reviewers, journal editors and readers.This explanatory and
      elaboration document is intended to enhance the use, understanding, and
      dissemination of the STROBE Statement. The meaning and rationale for each
      checklist item are presented. For each item, one or several published examples
      and, where possible, references to relevant empirical studies and methodological
      literature are provided. Examples of useful flow diagrams are also included. The
      STROBE Statement, this document, and the associated web site (http://www.strobe
      statement.org) should be helpful resources to improve reporting of observational
      research.

PMID- 18049196
TI  - Mort Levin and the emergence of chronic disease epidemiology.

PMID- 18049197
TI  - Irritable bowel syndrome and hysterectomy: a sequence symmetry analysis.

PMID- 18049198
TI  - Analyses of genome-wide association scans for additional outcomes.

PMID- 18049199
TI  - Do time-series studies contain residual confounding by risk factors for acute
      health events?

PMID- 18049201
TI  - Frequency of changing suction canisters and suction tubing: a descriptive study.
AB  - There is little evidence to suggest the appropriate frequency for changing
      suction canisters and tubing in the gastroenterology setting. This survey was
      initiated to determine whether there was a community standard for this issue. A
      diverse geographic response from attendees at the 2006 Society of
      Gastroenterology Nurses and Associates revealed that there is no current
      "standard of practice." Findings were diverse and are reported on the basis of
      the size of the facility, type of facility, number of endoscopic procedure rooms,
      and number of endoscopic procedures per month. The majority of respondents (91%)
      used disposable suction devices. The authors recommend the need for well
      designed, systematic studies to determine the appropriate frequency for changing
      suction canisters and tubing in the endoscopic setting.

PMID- 18049202
TI  - Complications of percutaneous endoscopic and fluoroscopic gastrostomy tube
      insertion procedures in 378 patients.
AB  - Gastrostomy tubes are used for primary and supplemental feeding and gastric
      decompression. The purpose of the study was to compare the complication rate of
      gastrostomy tube placement by either endoscopic or fluoroscopic technique.
      Between 1996 and 2004, the surgical and radiological services at a Level I trauma
      hospital placed gastrostomy tubes in 378 patients (endoscopy=268,
      fluoroscopy=110). The percutaneous gastrostomy group comprised 71% of the cohort
      with a mean age of 51+/-21 (range: 1-93 years of age), and the percutaneous
      radiographic gastrostomy group comprised the remaining cohort (29%) with a mean
      age of 57+/-19 (range: 17-95 years of age). Fifty-eight percent of the
      percutaneous gastrostomy group were female (n=155) and 42% were male (n=113),
      whereas the gender distribution for the percutaneous radiographic gastrostomy
      group was 33% female (n=36) and 67% male (n=74). There was an overall
      complication rate of 36% (22% and 70% for the endoscopic and fluoroscopic
      methods, respectively). The most frequent complication in both types of
      techniques was tube dislodgement (endoscopic=32% [19/268]; fluoroscopic=27%
      [21/110]). There were very few serious complications. Women had a higher rate of
      postprocedure complications than did men, at 35% versus 27%. We conclude that
      gastrostomy tube placement by either endoscopic or fluoroscopic methods results
      in a number of complications, though most of them are minor. Patients must
      therefore be informed that this is not a complication-free procedure.

PMID- 18049203
TI  - Methemoglobinemia and benzocaine.
AB  - Benzocaine administration to facilitate upper endoscopic procedures can result in
      the relatively uncommon but potentially fatal complication known as
      methemoglobinemia. For this reason, the Veterans Health Administration (VA)
      announced on February 8, 2006, that they would stop using benzocaine-containing
      sprays for procedures involving the mouth and throat. Methemoglobinemia should be
      considered in any patient who demonstrates cyanosis, respiratory distress,
      headache, lightheadedness, and a dark, chocolate-colored blood after receiving
      pharyngeal anesthesia. Prompt recognition of this rare (but potentially fatal)
      condition is important. Once identified, treatment is generally rapid with
      methylene blue. The patient should be monitored in the intensive care setting for
      recurrence. Knowledge of this adverse medication reaction is essential for all
      gastroenterology nurses.

PMID- 18049205
TI  - Helicobacter pylori strikes again: gastric mucosa-associated lymphoid tissue
      (MALT) lymphoma.
AB  - Infection with Helicobacter pylori is common. Over 50% of the world's population
      is estimated to be colonized with the bacteria. The association between
      Helicobacter pylori and gastric mucosa-associated lymphoid tissue (MALT) lymphoma
      is well documented. Anti-Helicobacter pylori treatment and the successful
      eradication of the bacteria can potentially cure patients who test positive for
      the bacteria and who are diagnosed with low-grade gastric MALT lymphoma. The
      purpose of this article is to review the evidence implicating Helicobacter pylori
      as a causal pathogen for the development of gastric MALT lymphoma and to
      determine that anti-Helicobacter pylori therapy is an effective first-line
      treatment. The clinical presentation, endoscopic findings, diagnosis, staging,
      treatment, and follow-up of patients with gastric MALT lymphoma who are treated
      with anti-Helicobacter pylori therapy are also discussed.

PMID- 18049207
TI  - Dietary intake and body composition of Japanese ulcerative colitis patients in
      remission.
AB  - The purpose of this pilot study (N=26) was to investigate dietary intake and body
      composition and problems associated with dietary intake (such as unnecessary
      dietary restriction) in Japanese patients in remission from ulcerative colitis.
      Findings revealed the macronutrient intake and dietary fiber (absolute amount)
      were lower than the national average in men, but this may have been due to
      differences in the methods used to measure dietary intake. Although the fat
      intake (%E) of ulcerative colitis patients in this study was similar to that of
      the Japanese population, it differed greatly from that of people in Western
      countries. No significant differences in weight, height, or body mass index were
      found when comparing the sample of individuals living with ulcerative colitis
      with the general Japanese population. Seventeen patients (65.4%) reported being
      cautious about what they ate even though in remission, and 6 patients were even
      more cautious about what they ate now than they had been in the past. The authors
      suggest further research to clarify the problems that unnecessary dietary
      restriction cause for ulcerative colitis patients who are in remission.

PMID- 18049209
TI  - Who will take your place?

PMID- 18049210
TI  - The great gluten escape: a camp for children with celiac disease.

PMID- 18049211
TI  - Are your measurements reliable?

PMID- 18049214
TI  - Lauriston S. Taylor lecture: fifty years of scientific research: the importance
      of scholarship and the influence of politics and controversy.
AB  - Over the past 50 years our laboratory has performed and published many studies in
      the fields of teratology, radiation biology and radiation embryology. The early
      work took place when I was a research employee at the University of Rochester
      Manhattan Project in 1944 and where I had my introduction to embryology and
      genetics. Over the years our lab has provided consultations dealing with the
      risks of various environmental toxicant exposures during pregnancy. With the
      advent of the Internet, consulting has become more rapid and efficient. In the
      past year our pregnancy Web site of the Health Physics Society received
      approximately 154,000 hits, of which over a thousand contacts were still quite
      anxious after reading the Web site answers and requested a personal consultation.
      From this extensive experience we have learned that many physicians and other
      counselors are not prepared to counsel patients concerning radiation risks.
      Approximately 8% of the patient contacts who have consulted a professional have
      been provided with inaccurate information that would have resulted in an
      unnecessary interruption of a wanted pregnancy. There are five areas of radiation
      embryology that are considered to be controversial. 1) Can the fetus be harmed by
      ionizing radiation if the fetus is not directly exposed? 2) Is the production of
      mental retardation from radiation during pregnancy a threshold phenomenon? 3)
      Does fractionation and protraction of radiation decrease the magnitude of the
      reproductive and developmental risks? 4) Is there a period during pregnancy when
      radiation will result in an increased mortality but not an increase in
      malformations? 5) How sensitive is the fetus to the oncogenic effects of
      radiation? We utilize the scientific information obtained from studies in these
      five areas to counsel patients concerning pregnancy radiation risks. The
      willingness and persistence of scientists to debate the controversial aspects of
      this research and apply the best available scientific information to assist
      patients in turmoil about the risks of radiation to themselves and their
      offspring has saved thousand of lives and changed family histories.

PMID- 18049216
TI  - Third annual Warren K. Sinclair keynote address: retrospective analysis of
      impacts of the Chernobyl accident.
AB  - The accident at the Chernobyl Nuclear Power Plant in 1986 was the most severe in
      the history of the nuclear industry, causing a huge release of radionuclides over
      large areas of Europe. The recently completed Chernobyl Forum concluded that
      after a number of years, along with reduction of radiation levels and
      accumulation of humanitarian consequences, severe social and economic depression
      of the affected regions and associated psychological problems of the general
      public and the workers had become the most significant problem to be addressed by
      the authorities. The majority of the >600,000 emergency and recovery operation
      workers and five million residents of the contaminated areas in Belarus, Russia,
      and Ukraine received relatively minor radiation doses which are comparable with
      the natural background levels. An exception is a cohort of several hundred
      emergency workers who received high radiation doses and of whom 28 persons died
      in 1986 due to acute radiation sickness. Apart from the dramatic increase in
      thyroid cancer incidence among those exposed to radioiodine at a young age and
      some increase of leukemia in the most exposed workers, there is no clearly
      demonstrated increase in the somatic diseases due to radiation. There was,
      however, an increase in psychological problems among the affected population,
      compounded by the social disruption that followed the break-up of the Soviet
      Union. Despite the unprecedented scale of the Chernobyl accident, its
      consequences on the health of people are far less severe than those of the atomic
      bombings of the cities of Hiroshima and Nagasaki. Studying the consequences of
      the Chernobyl accident has made an invaluable scientific contribution to the
      development of nuclear safety, radioecology, radiation medicine and protection,
      and also the social sciences. The Chernobyl accident initiated the global nuclear
      and radiation safety regime.

PMID- 18049217
TI  - Chernobyl radionuclide distribution and migration.
AB  - The accident at Unit No. 4 of the Chernobyl Nuclear Power Plant on 26 April 1986
      presented severe challenges in radiation protection. Early activity measurements
      defined the contaminated areas in order to determine what persons should be
      evacuated on the basis of the exposure limit at that time of 100 mSv (10 rem) for
      accidents. The immediate definition of these areas was accomplished with
      specially equipped aircraft capable of measuring external gamma-exposure rate and
      radionuclide spectra. Over time, maps of 137Cs contamination (the most important
      long-lived radionuclide) have become more and more sophisticated and have been
      used for further determinations of the control of the consequences of the
      accident. About 70% of the total release of 137Cs was deposited in Belarus, the
      Russian Federation, and Ukraine; but there was also widespread deposition
      throughout the countries of Western Europe. Two atlases of contamination
      throughout Europe were prepared, and the Russian atlas included data on other
      radionuclides and on external gamma-exposure rates. The radiocesiums behaved as
      volatile radionuclides because of the volatility of cesium. In contrast to the
      typical pattern after nuclear weapons tests, 90Sr behaved only as a refractory
      element, as its volatile precursors krypton and rubidium had already decayed
      within the reactor. Nearly all of the refractory elements (strontium, plutonium,
      etc.) released by the accident were confined to the 30-km zone around the
      reactor. A proposal is made to develop a more complete atlas of 137Cs deposition
      from the accident that would include the entire Northern Hemisphere. Water was
      not an important vector of exposure to human beings following the accident.

PMID- 18049218
TI  - Chernobyl radionuclide distribution, migration, and environmental and
      agricultural impacts.
AB  - The distribution and migration of radionuclides released into the environment
      following the Chernobyl accident in 1986 are described. The Chernobyl disaster
      resulted in the consumption of farm products containing radionuclides as a source
      of irradiation of the population due to the prevalence of a rural type of human
      nutrition in the affected region. Economic and radiologic importance of
      countermeasures for reducing the impacts of the accident are described. The basic
      radioecological problem is described in which the area where direct radiation
      contamination of biota was observed is considerably smaller than the zone where
      concentrations of radionuclides through the food chain exceeded the permissible
      standards. The radiation-induced effects in biota in the affected area are
      described. In the long-term post-accident period, the radionuclide distribution
      between components of ecosystems (including humans) and doses are considered in
      comparison to a technologically normal situation of nuclear power plant
      operation. This analysis demonstrates that if radiation standards protect humans,
      then biota are also adequately protected against ionizing radiation.

PMID- 18049219
TI  - Radiation-induced effects on plants and animals: findings of the United Nations
      Chernobyl Forum.
AB  - Several United Nations organizations sought to dispel the uncertainties and
      controversy that still exist concerning the effects of the Chernobyl accident. A
      Chernobyl Forum of international expertise was established to reach consensus on
      the environmental consequences and health effects attributable to radiation
      exposure arising from the accident. This review is a synopsis of the subgroup
      that examined the radiological effects to nonhuman biota within the 30-km
      Exclusion Zone. The response of biota to Chernobyl irradiation was a complex
      interaction among radiation dose, dose rate, temporal and spatial variation,
      varying radiation sensitivities of the different taxons, and indirect effects
      from other events. The radiation-induced effects to plants and animals within the
      30-km Exclusion Zone around Chernobyl can be framed in three broad time periods
      relative to the accident: an intense exposure period during the first 30 d
      following the accident of 26 April 1986; a second phase that extended through the
      first year of exposure during which time the short-lived radionuclides decayed
      and longer-lived radionuclides were transported to different components of the
      environment by physical, chemical and biological processes; and the third and
      continuing long-term phase of chronic exposure with dose rates<1% of the initial
      values. The doses accumulated, and the observed effects on plants, soil
      invertebrates, terrestrial vertebrates and fish are summarized for each time
      period. Physiological and genetic effects on biota, as well as the indirect
      effects on wildlife of removing humans from the Chernobyl area, are placed in
      context of what was known about radioecological effects prior to the accident.

PMID- 18049220
TI  - Radioactive waste management and environmental contamination issues at the
      Chernobyl site.
AB  - The destruction of the Unit 4 reactor at the Chernobyl Nuclear Power Plant
      resulted in the generation of radioactive contamination and radioactive waste at
      the site and in the surrounding area (referred to as the Exclusion Zone). In the
      course of remediation activities, large volumes of radioactive waste were
      generated and placed in temporary near-surface waste storage and disposal
      facilities. Trench and landfill type facilities were created from 1986-1987 in
      the Chernobyl Exclusion Zone at distances 0.5-15 km from the nuclear power plant
      site. This large number of facilities was established without proper design
      documentation, engineered barriers, or hydrogeological investigations and they do
      not meet contemporary waste-safety requirements. Immediately following the
      accident, a Shelter was constructed over the destroyed reactor; in addition to
      uncertainties in stability at the time of its construction, structural elements
      of the Shelter have degraded as a result of corrosion. The main potential hazard
      of the Shelter is a possible collapse of its top structures and release of
      radioactive dust into the environment. A New Safe Confinement (NSC) with a 100 y
      service life is planned to be built as a cover over the existing Shelter as a
      longer-term solution. The construction of the NSC will enable the dismantlement
      of the current Shelter, removal of highly radioactive, fuel-containing materials
      from Unit 4, and eventual decommissioning of the damaged reactor. More
      radioactive waste will be generated during NSC construction, possible Shelter
      dismantling, removal of fuel-containing materials, and decommissioning of Unit 4.
      The future development of the Exclusion Zone depends on the future strategy for
      converting Unit 4 into an ecologically safe system, i.e., the development of the
      NSC, the dismantlement of the current Shelter, removal of fuel-containing
      material, and eventual decommissioning of the accident site. To date, a broadly
      accepted strategy for radioactive waste management at the reactor site and in the
      Exclusion Zone, and especially for high level and long-lived waste, has not been
      developed.

PMID- 18049221
TI  - Physical dosimetry of chernobyl cleanup workers.
AB  - This paper presents a critical review of dosimetric monitoring practices during
      Chernobyl cleanup from 1986 to 1990. Dosimetric monitoring is considered in time
      evolution with respect to legislative background (including dose limits), methods
      of dose assessment, and coverage of workers with radiation monitoring programs as
      well as availability of data on individual doses of liquidators. Four large
      independent dosimetry services (Administration of Construction No. 605, Chernobyl
      Nuclear Power Plant, Production Association "Combinat," and the troops) had
      operated in Chernobyl covering different cohorts of cleanup workers with
      dosimetric monitoring of variable quality and comprehension. Extremes in this
      range were presented by the highly professional dosimetry service of the
      Administration of Construction No. 605 (USSR Ministry of Medium Machinery), which
      had provided total coverage of workers with high quality individual
      thermoluminescent dosimeter monitoring, and military (troops of the USSR Ministry
      of Defense) who had received the least precise group dosimetry, which, however,
      had covered the whole population of military cleanup workers. The main groups of
      liquidators are considered from the point of view of completeness and quality of
      their dosimetric data. Main gaps in dosimetric data and limitations of existing
      dose records are identified. The issues of evolution of dose limits and problems
      of monitoring internal and beta exposure are considered from the point of view of
      significance of these components and the need for missing information.

PMID- 18049222
TI  - Health effects in those with acute radiation sickness from the Chernobyl
      accident.
AB  - The Chernobyl accident resulted in almost one-third of the reported cases of
      acute radiation sickness (ARS) reported worldwide. Cases occurred among the plant
      employees and first responders but not among the evacuated populations or general
      population. The diagnosis of ARS was initially considered for 237 persons based
      on symptoms of nausea, vomiting, and diarrhea. Ultimately, the diagnosis of ARS
      was confirmed in 134 persons. There were 28 short term deaths of which 95%
      occurred at whole body doses in excess of 6.5 Gy. Underlying bone marrow failure
      was the main contributor to all deaths during the first 2 mo. Allogenic bone
      marrow transplantation was performed on 13 patients and an additional six
      received human fetal liver cells. All of these patients died except one
      individual who later was discovered to have recovered his own marrow and rejected
      the transplant. Two or three patients were felt to have died as a result of
      transplant complications. Skin doses exceeded bone marrow doses by a factor of 10
      30, and at least 19 of the deaths were felt to be primarily due to infection from
      large area beta burns. Internal contamination was of relatively minor importance
      in treatment. By the end of 2001, an additional 14 ARS survivors died from
      various causes. Long term treatment has included therapy for beta burn fibrosis
      and skin atrophy as well as for cataracts.

PMID- 18049223
TI  - Late cancer and noncancer risks among Chernobyl emergency workers of Russia.
AB  - The presented work summarizes data on estimated radiation risks among Chernobyl
      emergency workers of the Russian Federation. In 1991-1998, the excess relative
      risk (ERR) of death from malignant neoplasm was statistically significant: excess
      relative risk per 1 Gy (ERR/Gy)=2.11 with 95% confidence interval (CI) (1.31
      2.92). In 1991-2001, the ERR estimation for incident solid cancers gives a
      positive, but statistically insignificant value: ERR/Gy=0.34 with 95% CI (-0.39;
      1.22). In 1986-2003, radiation risk for leukemia incidence was investigated.
      During the first 10 y after the Chernobyl accident (1986-1996) the relative risk
      (RR) of leukemia (excluding chronic lymphocytic leukemia) was statistically
      significant: RR=2.2 with 95% CI (1.3-3.8) for emergency workers with doses>0.15
      Gy in comparison with less exposed workers. In 1986-2000, a statistically
      significant dose response was observed for incident cerebrovascular diseases:
      ERR/Gy=0.39, 95% CI=(0.004; 0.77). For doses>0.15 Gy a statistically significant
      risk of cerebrovascular diseases as a function of mean daily dose was observed:
      ERR per 0.1 Gy d(-1)=2.17 with 95% CI=(0.64; 3.69). Different but overlapping
      cohorts of Russian emergency workers were used for these estimations. No
      adjustments were made for recognized risk factors for cerebrovascular diseases.
      All results should be considered as preliminary.

PMID- 18049224
TI  - Worker health and safety issues in reinforcing the entombment of the Chernobyl
      reactor.
AB  - The paper provides an overview of current work involving the strengthening of the
      Sarcophagus over the Chernobyl Nuclear Power Plant destroyed 4th unit. It
      includes a brief summary of the types of work being performed, the radiological
      environment, the medical surveillance program, the protective measures being
      implemented, and the internal and external radiation monitoring program for the
      workers. Also, it presents a summary of the workplace monitoring data and the
      internal and external dosimetry data, and estimates of the total effective doses
      received by the workers during the work. The primary contribution to worker
      radiation doses was from external exposure. The maximum total effective doses
      received are 9.2 mSv mo(-1) and 17.4 mSv y(-1).

PMID- 18049226
TI  - Thyroid cancer incidence among people living in areas contaminated by radiation
      from the Chernobyl accident.
AB  - As a result of the Chernobyl nuclear power plant accident, massive amounts of
      radioactive materials were released into the environment and large numbers of
      individuals living in Belarus, Russia, and Ukraine were exposed to radioactive
      iodines, primarily 131I. Iodine-131 concentrated in the thyroid gland of
      residents of the contaminated areas, with children and adolescents being
      particularly affected. In the decade after the accident, a substantial increase
      in thyroid cancer incidence was observed among exposed children in the three
      affected countries, and compelling evidence of an association between pediatric
      thyroid cancer incidence and radiation exposure to the thyroid gland accumulated.
      The data currently available suggest that both the magnitude and patterns of
      thyroid cancer risk are generally consistent with those reported following
      external exposure. Based on data from case-control studies, iodine deficiency
      appeared to enhance the risk of developing thyroid cancer following exposure from
      Chernobyl. Results from a recent large cohort study, however, did not support
      these findings. Data on adult exposure are limited and not entirely consistent.
      Similarly, information on thyroid cancer risks associated with in utero exposure
      is insufficient to draw conclusions. The lack of information on these two
      population groups indicates an important gap that needs to be filled. Twenty
      years after the accident, excess thyroid cancers are still occurring among
      persons exposed as children or adolescents, and, if external radiation can be
      used as a guide, we can expect an excess of radiation-associated thyroid cancers
      for several more decades. Since considerable uncertainties about the long-term
      health effects from Chernobyl remain, continued follow-up of the exposed
      populations should provide valuable information.

PMID- 18049225
TI  - Radiation dosimetry for highly contaminated Belarusian, Russian and Ukrainian
      populations, and for less contaminated populations in Europe.
AB  - The explosions at the Chernobyl Nuclear Power Plant (CNPP) in Ukraine early in
      the morning of 26 April 1986 led to a considerable release of radioactive
      materials during 10 d. The cloud from the reactor spread many different
      radionuclides, particularly those of iodine (131I) and cesium (134Cs and 137Cs),
      over the majority of European countries, but the greatest contamination occurred
      over vast areas of Belarus, the Russian Federation and Ukraine. As the major
      health effect of Chernobyl is an elevated thyroid cancer incidence in children
      and adolescents, much attention has been paid to the thyroid doses resulting from
      intakes of 131I, which were delivered within 2 mo following the accident. The
      thyroid doses received by the inhabitants of the contaminated areas of Belarus,
      Russia, and Ukraine varied in a wide range, mainly according to age, level of
      ground contamination, milk consumption rate, and origin of the milk that was
      consumed. Reported individual thyroid doses varied up to approximately 40,000
      mGy, with average doses of a few to 1,000 mGy, depending on the area where people
      were exposed. In addition, the presence in the environment of long-lived 134Cs
      and 137Cs has led to a relatively homogeneous exposure of all organs and tissues
      of the body via external and internal irradiation, albeit at low rates. Excluding
      the thyroid doses, the whole-body (or effective) dose estimates for the general
      population accumulated during 20 y after the accident (1986-2005) range from a
      few millisieverts (mSv) to some hundred mSv with an average dose of approximately
      10 mSv in the contaminated areas of Belarus, Russia, and Ukraine. In other
      European countries, both the thyroid and the effective doses are, on average,
      much smaller.

PMID- 18049227
TI  - Leukemia following the Chernobyl accident.
AB  - The accident at the Chernobyl Nuclear Power Plant in Ukraine in 1986 led to a
      substantial increase of thyroid cancer among those exposed as children. The other
      cancer that is the most sensitive to the effects of ionizing radiation is
      leukemia, and this paper evaluates the evidence relating exposure to Chernobyl
      radioactivity and leukemia risk. Two types of objectives are identified, namely,
      scientific evidence and public health, and two approaches to addressing such
      objectives are discussed. Empirical studies in affected populations are
      summarized, and it is concluded that, possibly apart from Russian cleanup
      workers, no meaningful evidence of any statistical association between exposure
      and leukemia risk as yet exists. However, it is important to carry on with such
      studies to satisfy various public health objectives.

PMID- 18049228
TI  - Psychological and perceived health effects of the Chernobyl disaster: a 20-year
      review.
AB  - The mental health impact of Chernobyl is regarded by many experts as the largest
      public health problem unleashed by the accident to date. This paper reviews
      findings reported during the 20-y period after the accident regarding stress
      related symptoms, effects on the developing brain, and cognitive and
      psychological impairments among highly exposed cleanup workers. With respect to
      stress-related symptoms, the rates of depressive, anxiety (especially post
      traumatic stress symptoms), and medically unexplained physical symptoms are two
      to four times higher in Chernobyl-exposed populations compared to controls,
      although rates of diagnosable psychiatric disorders do not appear to be elevated.
      The symptom elevations were found as late as 11 y after the accident. Severity of
      symptomatology is significantly related to risk perceptions and being diagnosed
      with a Chernobyl-related health problem. In general, the morbidity patterns are
      consistent with the psychological impairments documented after other toxic
      events, such as the atomic bombings of Hiroshima and Nagasaki, the Three Mile
      Island accident, and Bhopal. With respect to the developing brain of exposed
      children who were in utero or very young when the accident occurred, the World
      Health Organization as well as American and Israeli researchers have found no
      significant associations of radiation exposure with cognitive impairments.
      Cognitive impairments in highly exposed cleanup workers have been reported by
      Ukrainian researchers, but these findings have not been independently confirmed.
      A seminal study found a significant excess death rate from suicide in cleanup
      workers, suggesting a sizable emotional toll. Given the magnitude and persistence
      of the adverse mental health effects on the general population, long-term
      educational and psychosocial interventions should be initiated that target
      primary care physicians, local researchers, and high risk populations, including
      participants in ongoing cohort studies.

PMID- 18049229
TI  - Rehabilitation of living conditions in territories contaminated by the Chernobyl
      accident: the ETHOS project.
AB  - The ETHOS Project, supported by the radiation protection research program of the
      European Commission (EC), was implemented in the mid-1990's with the support of
      the Belarus authorities as a pilot project to initiate a new approach for the
      rehabilitation of living conditions in the contaminated territories of the
      Republic. This initiative followed a series of studies performed in the context
      of the EC Community of Independent States cooperation program to evaluate the
      consequences of the Chernobyl accident (1991-1995), which clearly brought to the
      fore that a salient characteristic of the situation in these territories was the
      progressive and general loss of control of the population on its daily life.
      Furthermore, due to the economic difficulties during the years following the
      breakdown of the USSR, the population was developing private production and, in
      the absence of know-how and adequate means to control the radiological quality of
      foodstuffs, the level of internal exposure was rising significantly. The aim of
      the project was primarily to involve directly the population wishing to stay in
      the territories in the day-to-day management of the radiological situation with
      the goal of improving their protection and their living conditions. It was based
      on clear ethical principles and implemented by an interdisciplinary team of
      European experts with specific skills in radiation protection, agronomy, social
      risk management, communication, and cooperation in complex situations, with the
      support of local authorities and professionals. In a first phase (1996-1999), the
      ETHOS Project was implemented in a village located in the Stolyn District in the
      southern part of Belarus. During this phase, a few tens of villagers were
      involved in a step-by-step evaluation of the local radiological situation to
      progressively regain control of their daily life. In a second phase (1999-2001),
      the ETHOS Project was extended to four other localities of the District with the
      objective to evaluate the feasibility of the application of the ETHOS approach by
      local professionals and authorities. The ETHOS experience has shown that the
      direct involvement of the population in the day-to-day management of the
      radiological situation was a necessary approach to complement the rehabilitation
      program implemented by public authorities in contaminated territories. It also
      demonstrated that to be effective and sustainable, this involvement must rely on
      the dissemination of a "practical radiological protection culture" within all
      segments of the population, and especially among professionals in charge of
      public health and education. This paper discusses the post-Chernobyl context in
      the early- and mid-1990's, which led Belarus authorities to look for new
      approaches to protect the population residing in the long-term contaminated
      territories of the Republic. It then describes the ETHOS methodology and its main
      results. It also summarizes the general conclusions that can be drawn from the
      ETHOS Project.

PMID- 18049230
TI  - Lessons learned from Chernobyl and other emergencies: establishing international
      requirements and guidance.
AB  - In the past 25 years, nuclear and radiological emergencies have occurred that
      cover much of the range of causes and types that had been anticipated by experts.
      Experience from response to these emergencies has clearly demonstrated the
      importance of an efficient response system that includes, among other components,
      emergency plans, procedures, and internally consistent operational criteria. An
      analysis of lessons identified from recent responses has shown that a lack of
      crucial components in the emergency response system could result in major
      radiological and nonradiological consequences at the national level. A rigorous
      examination of the response to past emergencies has shown that there is a need
      for additional consistent international guidance on taking protective and other
      response actions and for placing the guidance in a context that is both
      comprehensive for the decision makers and can be explained to the public. This
      paper briefly describes the lessons learned from past radiation emergencies and
      how these lessons are used by the International Atomic Energy Agency in
      developing the international guidance in the area of emergency preparedness and
      response. In particular, the paper discusses the proposed extended framework of
      emergency response criteria. The framework is composed of two fundamental parts:
      (1) generic reference levels and (2) a plain language explanation for each
      generic reference level to assist the decisions makers and the public in making
      informed decisions on the actions they should take when this level is reached.
      The system of generic reference levels covers the full range of potential and
      actual exposures, from those levels that can result in severe deterministic
      health effects down to those that allow for a return to normality.

PMID- 18049231
TI  - Long-term health implications of the Chernobyl accident and relevant projects of
      the World Health Organization.
AB  - The past two decades have witnessed dramatic changes in public health governance
      and international cooperation on the Chernobyl Nuclear Power Plant accident,
      especially after the end of the Cold War. The World Health Organization (WHO) has
      committed itself deeply to the public health issues around Chernobyl and has
      participated in various health projects such as health monitoring and cancer
      screening. WHO has also been engaged in research activities such as the Chernobyl
      Tissue Bank, in close collaboration with the Ministries of Health in Belarus,
      Russia, and Ukraine. In addition to the official report of the Chernobyl Forum
      "Health Expert Groups" in 2005, the task of WHO is to not only analyze and
      clarify the global burden of Chernobyl-related illness, but also to promote the
      well-being of the local residents who suffered chronic low-level radiation
      exposure from radiation fallout.

PMID- 18049232
TI  - Current status and epidemiological research needs for achieving a better
      understanding of the consequences of the Chernobyl accident.
AB  - Twenty years after the Chernobyl accident, there is no clearly demonstrated
      increase in the incidence of cancers in the most affected populations that can be
      attributed to radiation from the accident, except for the dramatic increase in
      thyroid cancer incidence among those exposed in childhood and adolescence.
      Increases in the incidence of cancers and other diseases have been reported in
      Belarus, the Russian Federation, and Ukraine, but much of the increase appears to
      be due to other factors, including improvements in diagnosis, reporting, and
      registration. Recent findings indicate a possible doubling of leukemia risk among
      Chernobyl liquidators and a small increase in the incidence of premenopausal
      breast cancer in the very most contaminated districts. Increased risks of
      cardiovascular diseases and cataracts have also been reported. These findings,
      however, need confirmation in well-designed analytical epidemiological studies
      with careful individual dose reconstruction. The absence of demonstrated
      increases in cancer risk--apart from thyroid cancer--is not the proof that no
      increase has in fact occurred. Based on the experience of atomic bomb survivors,
      and assuming that there is a linear, no-threshold dose-response relationship
      between exposure to ionizing radiation and the development of cancer in humans, a
      small increase in the relative risk of cancer is expected, even at the low to
      moderate doses received. Given the large number of individuals exposed, the
      absolute number of cancer cases caused could be substantial, particularly in the
      future. It is therefore essential to continue to use population registries to
      monitor trends in disease morbidity and mortality in the most contaminated areas,
      as well as among liquidators, in order to assess the public health impact of the
      accident. Studies of selected populations and diseases are also essential in
      order to study the real effect of the accident and compare it to predictions.
      Careful studies may in particular provide important information on the effect of
      exposure rate and exposure type in the low to medium dose range and on factors
      that may modify radiation effects. As such, they may have important consequences
      for the radiation protection of patients and of the general population in case of
      further nuclear emergencies.

PMID- 18049233
TI  - New reactor technology: safety improvements in nuclear power systems.
AB  - Almost 450 nuclear power plants are currently operating throughout the world and
      supplying about 17% of the world's electricity. These plants perform safely,
      reliably, and have no free-release of byproducts to the environment. Given the
      current rate of growth in electricity demand and the ever growing concerns for
      the environment, nuclear power can only satisfy the need for electricity and
      other energy-intensive products if it can demonstrate (1) enhanced safety and
      system reliability, (2) minimal environmental impact via sustainable system
      designs, and (3) competitive economics. The U.S. Department of Energy with the
      international community has begun research on the next generation of nuclear
      energy systems that can be made available to the market by 2030 or earlier, and
      that can offer significant advances toward these challenging goals; in
      particular, six candidate reactor system designs have been identified. These
      future nuclear power systems will require advances in materials, reactor physics,
      as well as thermal-hydraulics to realize their full potential. However, all of
      these designs must demonstrate enhanced safety above and beyond current light
      water reactor systems if the next generation of nuclear power plants is to grow
      in number far beyond the current population. This paper reviews the advanced
      Generation-IV reactor systems and the key safety phenomena that must be
      considered to guarantee that enhanced safety can be assured in future nuclear
      reactor systems.

PMID- 18049234
TI  - Future challenges for nuclear power plant development research, and for
      radiological protection sciences.
AB  - The promise of the future shines brightly for nuclear energy technology and
      production, yet also holds many challenges. Focus on new reactor designs is
      currently aiming at what is termed the fourth generation of reactors, which will
      come into operation after 2030. The 10 countries participating in the Generation
      IV International Forum to develop the new generation of reactors have designated
      six reactor designs that will be studied. This paper will briefly discuss some of
      these challenges in new reactor designs in general. In addition to the challenges
      posed by new reactor designs, radiation protection is also faced with a series of
      challenges for the future. These are borne from experience with the
      implementation of the current system of radiological protection, from the
      evolution of radiation biological research, and from changes in society in the
      area of radiological risk assessment and management. This paper will address all
      of these emerging challenges, and point towards approaches to resolve them in the
      future.

PMID- 18049235
TI  - Moving to a low-carbon future: perspectives on nuclear and alternative power
      sources.
AB  - This paper summarizes key findings from climate science to make the case that the
      United States (and ultimately the world) will need to dramatically reduce carbon
      dioxide emissions from the energy system over the next few decades. While
      transportation energy is an important consideration, the focus of this paper is
      on electric power. Today, the United States generates just over half of its
      electric power from coal. The average size-weighted age of the fleet of U.S. coal
      plants is 35 y, and many will have to be replaced in the next few years. If that
      capacity were to be replaced with new conventional coal plants, it would commit
      the nation (and the world) to many more decades of high carbon-dioxide emissions,
      or it would make the cost of meeting a future carbon-dioxide emission constraint
      much higher than it needs to be. A range of low- and no-carbon energy
      technologies offers great potential to create a portfolio of options that can
      dramatically reduce emissions. A few of the advantages and disadvantages of these
      technologies are discussed. Policy and regulatory advances that will be needed to
      move the energy system to a low-carbon future are identified.

PMID- 18049236
TI  - Chernobyl vis-a-vis the nuclear future: an international perspective.
AB  - The paper aims to provide an international perspective on the consequences of the
      Chernobyl accident vis-a-vis the future development of the use of nuclear energy
      for peaceful purposes. It describes the major international initiatives that were
      undertaken over the years in order to quantify the consequences of the Chernobyl
      accident, and also analyzes the impact of the accident on the development of
      nuclear energy taking account of the perception of its consequences. The paper
      revisits the historical saga flowing since the fateful explosion at the Chernobyl
      Nuclear Power Plant in the Ukraine 20 y ago. It looks at some of the
      misunderstandings about the consequences of the accident and explores the
      worldwide nuclear stagnation that followed Chernobyl, surveying the negative
      public reaction and also the possibilities of a nuclear revival. It finally
      searches for a way forward, concluding that an effective international nuclear
      safety regime is urgently needed with the purpose of preventing catastrophes like
      Chernobyl from occurring and also that the Chernobyl consequences need to be
      readdressed properly. The paper concludes with an appeal to the radiation
      protection community to resolve once and for all the difficult issues of
      attributing health effects to low-level radiation exposure.

PMID- 18049242
TI  - RSO Interview with Thomas Morgan by Rene Michel.

PMID- 18049243
TI  - Release limits and decontamination efficacy for tritium: lessons learned outside
      nuclear power operations.
AB  - Various pieces of equipment in use by the Canadian Department of National Defence
      (DND) contain radiation-emitting components. One such piece is a sight knob used
      on light artillery. At the request of the DND's Director General Nuclear Safety
      (DGNS-DND's internal nuclear regulatory agency), the authors were contacted to
      remove the luminous tritium-impregnated paint strip from over 300 sight knobs.
      This paper discusses the physical description of the sight knobs, the protocol
      developed for decontaminating the sight knobs, the rationale for the release
      limits used, and experience gained in using and modifying the decontamination
      protocol.

PMID- 18049244
TI  - An Overview of 137Cs Contamination in a Southeastern Swamp Environment.
AB  - In the early 1960's, an area of privately owned swamp adjacent to the Savannah
      River Site was contaminated by site operations. Studies conducted in 1974
      estimated that approximately 925 GBq of Cs and 37 GBq of Co were deposited in the
      swamp. Subsequently, a series of surveys was initiated to characterize the
      contaminated environment. These surveys-composed of 52 monitoring locations-allow
      for continued monitoring at a consistent set of locations. Initial survey results
      indicated maximum Cs concentrations of 19.5 Bq g in soil and 8.7 Bq g in
      vegetation. By the 2004-2005 surveys, maximum concentrations had declined to 1-2
      Bq g in soil and 0.4 Bq g in vegetation.

PMID- 18049245
TI  - Aerosol collection of the (Bladewerx Corporation) breathing zone monitor and
      portable workplace monitor.
AB  - The Radiation Protection Group at the Los Alamos National Laboratory has a wind
      tunnel capable of measuring the aerosol collection efficiencies of air sampling
      devices. In the fall of 2005, the group received an internal Los Alamos request
      to perform aerosol collection efficiency tests on two air samplers manufactured
      by the Bladewerx Corporation (Rio Rancho, NM). This paper presents the results
      from tests performed in the wind tunnel facility at a test velocity of 0.5 m s.
      The SabreAlert (Portable Workplace Monitor) and the SabreBZM (Breathing Zone
      Monitor) are both designed to detect and measure the presence of alpha emitting
      isotopes in atmospheres. The SabreAlert was operated at two test air flow rates
      of 6 and 45 liters per minute (LPM), and the SabreBZM was operated at two test
      air flow rates of 3 and 19 LPM. The aerosol collection efficiencies of both
      samplers were evaluated with oleic acid (monodisperse) liquid droplet aerosols
      tagged with sodium fluorescein tracer. These test aerosols varied in size from
      about 2.3 to 17.2 microns (aerodynamic equivalent diameter). The SabreAlert was
      roughly 100% efficient in aerosol collection at a flow rate of 6 LPM, and had an
      aerodynamic cutpoint diameter of 11.3 microns at the 45 LPM flow rate. The
      SabreBZM had an aerodynamic cutpoint diameter of 6.7 microns at the 3 LPM flow
      rate, but the SabreBZM aerosol collection efficiency never exceeded 13.6% at the
      19 LPM test flow rate condition.

PMID- 18049246
TI  - Nondestructive characterization of radioactive waste drums by gamma spectrometry:
      a Monte Carlo technique for efficiency calibration.
AB  - A semi-empirical non-destructive technique to assay radioactive waste drums is
      presented. The technique is based on gamma spectrometry performed using a
      portable NaI detector and Monte Carlo simulations using the MCNP code in order to
      derive the gamma ray detector efficiency for the volume source. The derivation of
      detector efficiency was performed assuming homogeneous distribution of the source
      activity within the matrix material. Moreover, the MCNP model was used to examine
      the effect of inhomogeneities in activity distribution, variation of matrix
      material density, and drum filling height on the accuracy of the technique, and
      to estimate the measurement bias. The technique was verified by estimating
      radioactivity levels in 25 drums containing ion exchange resin waste, and
      comparing the results of the non-destructive method against the analytical
      results of samples obtained from each drum. Satisfactory agreement between the
      two assay techniques was observed. The discussed technique represents a cost
      effective technology that can be used to assay low-activity, low-density waste
      drums provided the contribution to the gamma ray spectrum can be resolved.

PMID- 18049247
TI  - The Human Monitoring Laboratory's whole body counter: monitoring the liquid
      nitrogen level as a quality control tool.
AB  - The Human Monitoring Laboratory (HML) has developed a method to measure the
      liquid nitrogen boil-off rate from the whole body counter's single dewar as a
      function of time. The device consists of a commercially available instrument that
      was modified to fit the HML's whole body counter's dewar; unfortunately, the
      modification was not perfect requiring an alternative approach to using the
      maximum fill value. The boil-off rate is now measured by taking two measurements
      and calculating the loss rate. Resulting boil-off rates are plotted on a control
      chart so that long-term trends can be easily assessed.

PMID- 18049248
TI  - Field evaluations of digital radon detectors.
AB  - Recently, digital radon detectors were made available on the market for
      homeowners at a cost comparable to that charged by some service providers for a
      single radon test. Digital radon detectors provide an easy and less expensive way
      for homeowners to monitor radon levels in their homes. In order to answer a
      frequently asked question regarding the performance of such low-cost electronic
      radon detectors, field evaluations were conducted. Evaluation results are
      reported here.

PMID- 18049249
TI  - The roles of medical health physicists in a medical radiation emergency.
AB  - Medical health physicists working in a clinical setting will have a number of key
      roles in the event of a nuclear or radiological emergency, such as a terrorist
      attack involving a radiological dispersal device or an improvised nuclear device.
      Their first responsibility, of course, is to assist hospital administrators and
      facility managers in developing radiological emergency response plans for their
      facilities and train staff prior to an emergency. During a hospital's response to
      a nuclear or radiological emergency, medical health physicists may be asked to
      (1) evaluate the level of radiological contamination in or on incoming victims;
      (2) help the medical staff evaluate and understand the significance to patient
      and staff of the levels of radioactivity with which they are dealing; (3) orient
      responding medical staff with principles of dealing with radioactive
      contaminants; (4) provide guidance to staff on decontamination of patients,
      facilities, and the vehicles in which patients were transported; and (5) assist
      local public health authorities in monitoring people who are not injured but who
      have been or are concerned that they may have been exposed to radioactive
      materials or radiation as a result of the incident. Medical health physicists may
      also be called upon to communicate with staff, patients, and the media on
      radiological issues related to the event. Materials are available from a number
      of sources to assist in these efforts. The Centers for Disease Control and
      Prevention (CDC) is developing guidance in the areas of radiological population
      monitoring, handling contaminated fatalities, and using hospital equipment for
      emergency monitoring. CDC is also developing training and information materials
      that may be useful to medical health physicists who are called upon to assist in
      developing facility response plans or respond to a nuclear or radiological
      incident. Comments on these materials are encouraged.

PMID- 18049250
TI  - Infection prevention and control.

PMID- 18049251
TI  - Turning caring into business: the nuts and bolts of starting a private-duty home
      care business.
AB  - As baby boomers age and home care grows in popularity as an alternative to
      institutionalized care, opportunities abound for entrepreneurs to meet the demand
      through professional private-duty businesses. This article examines the nuts and
      bolts of launching and operating a successful private-duty agency.

PMID- 18049252
TI  - Netting the hospice butterfly: politics, policy, and translation of an ideal.
AB  - This article presents a historical analysis of the American hospice movement. It
      examines the social and political factors that created an environment for the
      movement to emerge. In doing so, it explores the processes by which
      multidisciplinary teams came together to advance hospice as a necessary
      healthcare reform and the challenges they faced in doing so.

PMID- 18049253
TI  - Comparison of three single-person manual patient techniques for bed-to-wheelchair
      transfers.
AB  - The uniqueness of the home environment still requires home health clinicians to
      lift and transfer patients manually, tasks that are known to cause back injuries.
      Three manual patient transfers were evaluated to establish the technique with the
      least risk to the low back. Patient and worker perceptions as well as
      preferences, exposure duration, and a biomechanical low back evaluation are
      presented, together with transfer technique recommendations.

PMID- 18049254
TI  - Managing multidrug-resistant organisms in home care and hospice: surveillance,
      prevention, and control.
AB  - Multidrug-resistant organisms (MDROs), including methicillin-resistant
      Staphylococcus aureus, vancomycin-resistant enterococci, and certain gram
      negative bacilli, are transmitted most frequently in acute care facilities.
      However, these MDROs have important infection control implications for care
      provided in the home setting. Little is known about the actual occurrence of
      MDROs among home care and hospice patients. To date, no published reports have
      described transmission of an MDRO from care provided in the home setting.
      Nonetheless, all providers of care in the home should be aware of MDROs and the
      potential for their transmission from one patient to another. The Centers for
      Disease Control and Prevention's (CDC) Guideline on the Management of Multidrug
      Resistant Organisms in Healthcare Settings, 2006 provides recommendations for
      preventing and controlling the transmission of MDROs. This article discusses the
      Guideline's recommendations and how they may be implemented in the home setting
      by home health agencies, home infusion providers, hospices, and providers of
      durable medical equipment.

PMID- 18049256
TI  - Biofilms on medical devices.
AB  - Biofilm consists of microorganisms with altered phenotypes living in a self
      organized, cooperative community attached to surfaces and each other and embedded
      in a self-produced matrix of exopolymer saccharides. Biofilms are relevant for
      home care and hospice clinicians because they are related to the majority of
      infectious diseases. Colonization of medical devices plays a key role in the
      problem of healthcare-associated infections. This article aims to provide an
      overview of the science of biofilms. Understanding biofilms and the risks
      associated with them is the first step toward prevention of biofilm formation and
      the potentially serious outcomes of infections.

PMID- 18049257
TI  - Code Flu: common-sense steps to the development of an agency pandemic flu plan
      for home care.
AB  - Calling a code is a common way to sound the alarm of an emergency. Many kinds of
      codes exist: for patients who arrest, for fires, and for babies who have gone
      missing, to name a few. This article proposes a new code, Code Flu, which will
      alert staff, patients, cooperating and referring agencies, and members of the
      community that they are to operate under the preplanned pandemic flu plan.
      Suggestions for developing a Code Flu plan are outlined.

PMID- 18049258
TI  - Dangers of used sharps in household trash: implications for home care.
AB  - Between 8 and 9 million Americans are self-injecting medication at home, and the
      majority of the needles used are being thrown into the household trash. It is up
      to all stakeholders, including healthcare professionals, to help change the way
      these dangerous needles and other sharps are discarded. Are you giving your
      patients the correct information?

PMID- 18049263
TI  - A study of deaths associated with anesthesia and surgery. 1954.

PMID- 18049264
TI  - The contribution of anesthesia to surgical mortality.

PMID- 18049265
TI  - Experimental pharmacology and measurement of the subjective response. 1952.

PMID- 18049266
TI  - Pain and subjective responses.

PMID- 18049267
TI  - Surgery as placebo: a quantitative study of bias. 1961.

PMID- 18049268
TI  - Quintessential Beecher: Surgery as placebo: a quantitative study of bias. J Am
      Med Assoc. 1961;176:1102-1107.

PMID- 18049269
TI  - Ethics and clinical research. From the anaesthesia laboratory of the Harvard
      Medical School at the Massachusetts General Hospital. 1966.

PMID- 18049270
TI  - Recruiting allies for reform: Henry Knowles Beecher's "Ethics and clinical
      research".

PMID- 18049271
TI  - From LSD to the IRB: Henry Beecher's psychedelic research and the foundation of
      clinical ethics.

PMID- 18049272
TI  - A definition of irreversible coma. 1968.

PMID- 18049273
TI  - Defining brain death: motivations and future directions.

PMID- 18049274
TI  - Henry K. Beecher--his life in part: the Kansas years.

PMID- 18049277
TI  - Efferent visual dysfunction from multiple sclerosis.

PMID- 18049278
TI  - Historical perspective and future prospective for retinal nerve fiber loss in
      optic neuritis and multiple sclerosis.

PMID- 18049279
TI  - Optic neuropathy from bacteria.

PMID- 18049280
TI  - Optic neuropathy from viruses and spirochetes.

PMID- 18049281
TI  - Neuro-ophthalmologic manifestations of sarcoidosis.

PMID- 18049282
TI  - Orbital inflammatory disease.

PMID- 18049283
TI  - Ocular myasthenia gravis.

PMID- 18049284
TI  - Giant cell arteritis.

PMID- 18049285
TI  - Prion disease.

PMID- 18049286
TI  - Uveo-meningeal syndromes.

PMID- 18049287
TI  - The use of biologics and other immunosuppressants in the treatment of common
      inflammatory diseases in neuro-ophthalmology.

PMID- 18049289
TI  - 10-year research update review: psychiatric problems in children with epilepsy.
AB  - OBJECTIVE: To critically review literature published from 1996 to 2007 on
      psychopathology in children with epilepsy (CWE). METHOD: Using Ovid, we searched
      Medline and PsychInfo databases for original studies on epidemiology, risk
      factors, clinical characteristics, treatment, and outcome of psychopathology in
      CWE, ages 0 to 18 years, using the terms "psychopathology," "emotional and
      behavioral problems," and "mental health problems." We selectively present the
      findings of studies that are clinically relevant to mental health professionals.
      RESULTS: Psychopathology occurs in 37% to 77% of CWE, and attention,
      internalizing, and thought problems may be specific to epilepsy. Cognitive and
      linguistic deficits, as well as family factors, have moderating effects on
      psychopathology in CWE. The association of epilepsy-related variables, including
      antiepileptic drugs, with psychopathology is inconsistent in cognitively normal
      CWE. Children with symptomatic epilepsy and devastating epilepsy syndromes have
      high rates of global developmental delay, hyperactivity, and autistic symptoms.
      The treatment of psychopathology in CWE integrates standard psychiatric
      practices. CONCLUSIONS: Epilepsy is a neuropsychiatric disorder characterized by
      seizures, psychopathology, cognitive, and linguistic problems. Improved early
      identification of CWE at risk for psychopathology, evidence-based psychiatric
      treatment, and multidisciplinary management strategies would advance clinical
      practice in this highly complex field of pediatric neuropsychiatry.

PMID- 18049290
TI  - Cognitive-behavioral therapy for adolescent depression: a meta-analytic
      investigation of changes in effect-size estimates.
AB  - OBJECTIVE: To explicate differences between early and recent meta-analytic
      estimates of the effects of cognitive-behavioral therapy (CBT) for adolescent
      depression. METHOD: Meta-analytic procedures were used to investigate whether
      methodological characteristics moderated mean effect sizes among 11 randomized,
      controlled trials of CBT focusing on adolescents meeting diagnostic criteria for
      unipolar depression. RESULTS: Cumulative meta-analyses indicated that effects of
      CBT have decreased from large effects in early trials, and confidence intervals
      have become narrower. Effect sizes were significantly smaller among studies that
      used intent-to-treat analytic strategies, compared CBT to active treatments, were
      conducted in clinical settings, and featured greater methodological rigor based
      on CONSORT (Consolidated Standards of Reporting Trials) criteria. The mean
      posttreatment effect size of 0.53 was statistically significant. CONCLUSIONS:
      Differences in estimates of the efficacy of CBT for depressed adolescents may
      stem from methodological differences between early and more recent
      investigations. Overall, results support the effectiveness of CBT for the
      treatment of adolescent depression.

PMID- 18049291
TI  - Is stacking intervention components cost-effective? An analysis of the Incredible
      Years program.
AB  - OBJECTIVE: Research demonstrates that interventions targeting multiple settings
      within a child's life are more effective in treating or preventing conduct
      disorder. One such program is the Incredible Years Series, which comprises three
      treatment components, each focused on a different context and type of daily
      social interaction that a child encounters. This article explores the cost
      effectiveness of stacking multiple intervention components versus delivering
      single intervention components. METHOD: The data involved 459 children, ages 3 to
      8, who participated in clinical trials of the Incredible Years Series. Children
      randomized to one of six treatment conditions received one or more of the three
      following program components: a child-based program, a parent training program,
      and a teacher-based program instructing teachers in classroom management and in
      the delivery of a classroom-based social skills curriculum. RESULTS: Per-child
      treatment costs and child behavior outcomes (observer and teacher reported) were
      used to generate cost-effectiveness acceptability curves; results suggest that
      stacking intervention components is likely cost-effective, at least for
      willingness to pay above $3,000 per child treated. CONCLUSIONS: Economic data may
      be used to compare competing intervention formats. In the case of this program,
      providing multiple intervention components was cost-effective.

PMID- 18049293
TI  - Executive function in adolescents with ADHD.
AB  - OBJECTIVE: The aim of this study was to clarify executive function weakness in
      attention-deficit/hyperactivity disorder (ADHD) during adolescence and determine
      the specificity of executive function weakness to ADHD symptom domains. METHOD: A
      total of 182 adolescents (105 boys), ages 13 to 17 years, completed a multistage
      diagnostic assessment; 85 were diagnosed with ADHD: 43 primarily Inattentive type
      (ADHD-PI) and 42 Combined type (ADHD-C). Participants completed the Stop, Trail
      Making, Wisconsin Card Sort, and Stroop tasks. RESULTS: The ADHD group exhibited
      impaired performance compared with the non-ADHD group on executive function
      measures (multivariate p < .05); there were no ADHD subtype differences. A
      composite executive function factor was significantly related to inattentive but
      not hyperactive-impulsive symptoms. CONCLUSIONS: Executive function weakness in
      adolescent ADHD is specifically related to symptoms of inattention
      disorganization. Results are congruent with a dual-pathway model of ADHD
      cognitive mechanisms.

PMID- 18049292
TI  - DSM-IV diagnoses and obstructive sleep apnea in children before and 1 year after
      adenotonsillectomy.
AB  - OBJECTIVE: Obstructive sleep apnea, a common indication for adenotonsillectomy in
      children, has been linked to behavioral morbidity. We assessed psychiatric
      diagnoses in children before and after adenotonsillectomy and examined whether
      baseline sleep apnea predicted improvement after surgery. METHOD: Subjects of
      this prospective cohort study were children ages 5.0 to 12.9 years old who had
      been scheduled for adenotonsillectomy (n = 79) or care for unrelated surgical
      conditions (n = 27, among whom 13 had surgery after baseline assessment). Before
      intervention and 1 year later, subjects underwent structured diagnostic
      interviews and polysomnography. The main outcome measure was frequency of DSM-IV
      attention and disruptive behavior disorder diagnoses at baseline and follow-up.
      RESULTS: At baseline, attention and disruptive behavior disorders were diagnosed
      in 36.7% of adenotonsillectomy subjects and 11.1% of controls (p < .05);
      attention-deficit/hyperactivity disorder was found in 27.8% and 7.4%,
      respectively (p < .05). One year later, group differences were nonsignificant;
      attention and disruptive behavior disorders were diagnosed in only 23.1% (p <
      .01), and 50% of subjects with baseline attention-deficit/hyperactivity disorder
      no longer met diagnostic criteria. Obstructive sleep apnea on polysomnography at
      baseline did not predict concurrent psychiatric morbidity or later improvement.
      CONCLUSIONS: Attention and disruptive behavior disorders, diagnosed by DSM-IV
      criteria, were more common before clinically indicated adenotonsillectomy than 1
      year later. Surgery may be associated with reduced morbidity, even among subjects
      lacking polysomnographic evidence of obstructive sleep apnea.

PMID- 18049294
TI  - Methylphenidate in the treatment of children and adolescents with bipolar
      disorder and attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To examine the short-term efficacy of methylphenidate in the treatment
      of youths with bipolar disorder (BD) and comorbid attention deficit/hyperactivity
      disorder (ADHD). METHOD: A 4-week double-blind, placebo-controlled trial in
      youths ages 5 to 17 years was conducted. Subjects met DSM-IV criteria for bipolar
      disorder and ADHD, were currently receiving a stable dose of at least one
      thymoleptic, and while euthymic continued to have clinically significant symptoms
      of ADHD. Patients received 1 week each of placebo, methylphenidate 5 mg twice
      daily, methylphenidate 10 mg twice daily, and methylphenidate 15 mg twice daily
      using a crossover design. Subjects were randomly assigned to receive one of six
      possible dosing orders. At study's end, and before the blind being broken, a
      "best dose week" for each subject was determined. The primary outcome measure was
      the total score on the parent-completed ADHD Rating Scale-IV. RESULTS: Sixteen
      patients, with a mean age of 10.43 (SD 3.14) years completed the trial. Lower
      scores during best dose treatment compared to the week of placebo treatment were
      found on the ADHD Rating Scale-IV (p < .05), suggesting a therapeutic benefit. A
      large effect size (Cohen's d = 0.90) was found for methylphenidate. Treatment was
      generally well tolerated. CONCLUSIONS: Euthymic youths with bipolar disorder and
      ADHD may benefit from short-term concomitant treatment with methylphenidate.

PMID- 18049295
TI  - Maternal stress during pregnancy predicts cognitive ability and fearfulness in
      infancy.
AB  - OBJECTIVE: To examine the effects of prenatal stress on cognition and behavioral
      fearfulness in infants. METHOD: Mothers were recruited at amniocentesis at Queen
      Charlotte's and Chelsea Hospital, London, between 2001 and 2005, and recalled
      when their children were 14 to 19 months to assess cognitive development using
      the Bayley Scales and fearfulness using the Lab-TAB. Measures of prenatal and
      postnatal life events and current psychological state were collected at the
      postnatal visit. RESULTS: Prenatal stress predicted both mental development (rs =
      -0.39, n = 123 p < .0001) and observed fearfulness (rs = 0.33, n = 106, p <
      .001); the magnitude of effect was essentially unchanged after covarying
      postnatal stressors, maternal education and psychological state, exposures to
      medications and substances during pregnancy, and birth outcomes. Prenatal stress
      accounted for 17% of the variance in cognitive ability and 10% of the variance in
      observed fearfulness. The correlation between mental development and fearfulness
      was minimal (r = -0.06, not significant). Prenatal partner relationship strain
      accounted for 73.5% and 75.0% of the prenatal stress related variance on infant
      cognitive and fearfulness scores, respectively. CONCLUSIONS: These findings
      strengthen previous research that suggests that fetal programming can be
      important for neurodevelopmental and psychiatric outcomes. They imply that the
      mechanisms by which mental development and fearfulness are affected are different
      and that prenatal stress due to relationship strain may warrant particular
      attention.

PMID- 18049296
TI  - Selective mutism and social anxiety disorder: all in the family?
AB  - OBJECTIVE: To examine the history of lifetime psychiatric disorders in the
      parents of children with selective mutism (SM) compared to parents of children in
      a control group. METHOD: Seventy parent dyads (n = 140) of children with lifetime
      SM and 31 parent dyads (n = 62) of children without SM were interviewed with the
      Structured Clinical Interview for DSM-IV (IV and II) anxiety disorders, mood
      disorders, avoidant personality disorder, and schizoid personality disorder
      modules via telephone. Interviewers were blind to proband status. The NEO
      Personality Inventory was also administered. RESULTS: Lifetime generalized social
      phobia was present in 37.0% of SM parents compared to 14.1% of control parents
      (chi2 = 10.98; p < .001; odds ratio 3.6, 95% confidence interval 1.6-7.9).
      Avoidant personality disorder was present in 17.5% of the SM parents compared to
      4.7% of control parents (chi2 = 6.18; p < .05; odds ratio 4.3, 95% confidence
      interval 1.3-14.9). The proportion of parents with other psychiatric disorders
      was not different between groups. SM parents had higher neuroticism and lower
      openness scores on the NEO Personality Inventory than control parents.
      CONCLUSIONS: These results support earlier uncontrolled findings of a familial
      relationship between generalized social phobia and SM.

PMID- 18049297
TI  - Long-term associations of childhood suicide ideation.
AB  - OBJECTIVE: We investigated in a prospective longitudinal population-based study
      whether childhood suicide ideation is associated with negative mental health
      outcome in adulthood. METHOD: A total of 1,022 Dutch children who were 11 years
      or younger in 1983 were prospectively followed over 10 to 14 years into
      adulthood. Parent reports of suicide ideation in childhood (11 years or younger;
      n = 20) were examined in relation to mental health in adulthood assessed with a
      structured psychiatric interview (mood disorder, anxiety disorder, alcohol
      abuse/dependence, and externalizing disorder) and self-reported suicide ideation
      and history of suicide attempt. RESULTS: Childhood suicide ideation was highly
      predictive of suicide ideation in adulthood (odds ratio 10.70, 95% confidence
      interval 3.26-35.09), and lifetime history of suicide attempt (odds ratio 5.80,
      95% confidence interval 1.53-22.02). Childhood suicide ideation was associated
      with an increased likelihood of mood disorder and anxiety disorder in adulthood
      and to a lesser extent externalizing disorder, although these effects decreased
      considerably after adjusting for childhood internalizing and externalizing
      behavior. CONCLUSIONS: Suicide ideation in childhood may be a stable
      characteristic with worrying consequences in adulthood. Children with parent
      reported suicide ideation at a young age may require additional resources, age
      appropriate intervention, and careful monitoring into adulthood.

PMID- 18049298
TI  - Validation of the Children's Interview for Psychiatric Syndromes (ChIPS) with
      psychiatrically hospitalized adolescents.
AB  - OBJECTIVE: To examine the concurrent validity of the Children's Interview for
      Psychiatric Syndromes (ChIPS) for adolescent inpatients. METHOD: Participants
      included 97 adolescents ages 12 to 18 admitted to an adolescent inpatient unit.
      Participants were administered the ChIPS and the Schedule for Affective Disorders
      and Schizophrenia for School-Age Children-Present and Lifetime version (present
      questions only). Participants also completed self-report measures of adjustment
      (e.g., the Reynolds Adolescent Depression Scale-2). RESULTS: More diagnoses were
      made with the ChIPS (mean 4.44) compared to the Schedule for Affective Disorders
      and Schizophrenia for School-Age Children-Present and Lifetime version (mean
      3.04; p <.001). The percentage of agreement ranged from 59% to 98%. Kappa
      coefficients indicated agreement ranging from slight for oppositional defiant
      disorder (kappa = .18) to substantial for substance use (kappa = .66); the
      majority of kappa values ranged from .26 to.60. When ChIPS endorsements were
      examined relative to construct-specific self-report measures of impairment,
      adolescents diagnosed by the ChIPS with a disorder scored significantly higher
      than adolescents who were not diagnosed with a disorder. CONCLUSIONS: The
      findings indicate moderate agreement between ChIPS diagnoses and Schedule for
      Affective Disorders and Schizophrenia for School-Age Children-Present and
      Lifetime version diagnoses. ChIPS diagnoses appear consistent with self-report
      measures of adjustment.

PMID- 18049299
TI  - Multidisciplinary management of pediatric nonepileptic seizures.

PMID- 18049300
TI  - Practice parameter for the assessment and treatment of children and adolescents
      with depressive disorders.
AB  - This practice parameter describes the epidemiology, clinical picture,
      differential diagnosis, course, risk factors, and pharmacological and
      psychotherapy treatments of children and adolescents with major depressive or
      dysthymic disorders. Side effects of the antidepressants, particularly the risk
      of suicidal ideation and behaviors are discussed. Recommendations regarding the
      assessment and the acute, continuation, and maintenance treatment of these
      disorders are based on the existent scientific evidence as well as the current
      clinical practice.

PMID- 18049301
TI  - Short patent lives jeopardize drug and patient safety.
AB  - Exposure of patients to new medications carries potential safety hazards during
      widespread clinical practice. These are often detected only after a substantial
      period of use. Thus, there is considerable need for measures reducing drug
      related morbidity and mortality, such as adequate, active postmarketing drug
      safety surveillance systems with obligatory follow-up studies of suspected safety
      problems, or even an additional "Phase IV" safety study before marketing.
      However, drug development processes erode substantially into the useful patent
      life of a new drug. Therefore, we suggest that the potential benefits of patent
      life prolongation should be considered, under certain conditions for the sake of
      patient safety.

PMID- 18049302
TI  - Analysis of vasodilator responses to peroxynitrite in the hindlimb vascular bed
      of the cat.
AB  - The free radical peroxynitrite (ONOO-) is formed in biological systems from the
      reaction of nitric oxide (NO) with superoxide (O2-) and can react with protein
      and nonprotein thiol groups to produce tissue injury. However, these pathologic
      actions of (ONOO-) may have been overemphasized, in that (ONOO-) has vasorelaxant
      properties through activation of soluble guanylate cyclase; inhibits leukocyte
      endothelial cell interactions; and reduces ischemia-reperfusion injury in the
      heart, lung, and liver. It has been reported that tolerance develops to the
      vasodilator actions of (ONOO-) and that (ONOO-) impairs vascular function.
      However, little, if anything, is known about responses to (ONOO-) in the hindlimb
      circulation of the cat. To better understand the effects of (ONOO-) on responses
      to vasoactive agonists and the mechanism by which (ONOO-) induces vasodilation,
      the effects of short-term exposure to (ONOO-) were investigated under constant
      flow conditions in the hindlimb vascular bed of the cat. In these studies, direct
      intraarterial injections of (ONOO-) produced dose-dependent decreases in
      hindquarters perfusion pressure. The vasodilator responses to (ONOO-) were rapid
      in onset, were short in duration, and could be repeated without exhibiting
      tachyphylaxis. Vasodilator responses to (ONOO-) were not changed in the presence
      of inhibitors of nitric-oxide synthase, cyclooxygenase, or K+-ATP (adenosine
      triphosphate-sensitive potassium) channels. Furthermore, responses to (ONOO-)
      were enhanced in duration by the type 5-cGMP (cyclic guanosine monophosphate)
      phosphodiesterase inhibitor zaprinast, whereas rolipram, a type 4-cGMP
      phosphodiesterase inhibitor, was without effect. Repeated administration of (ONOO
      ) had no significant effect on responses to vasoconstrictor or to vasodilator
      agents including acetylcholine. These results show that (ONOO-) has significant
      vasodilator activity in the hindlimb vascular bed of the cat and suggest that the
      response is mediated by a cGMP- dependent mechanism. The results of experiments
      with repeated injections of (ONOO-) indicate that (ONOO-) does not impair
      vasoconstrictor and endothelium-dependent or endothelium-independent vasodilator
      responses. Furthermore, tolerance did not develop with repeated short-term
      exposure to (ONOO-). Moreover, the results of experiments with inhibitors suggest
      that responses to (ONOO-) are not dependent on K-ATP (adenosine triphosphate
      sensitive potassium) channel activation, increased NOS activity, or the formation
      of products in the cyclooxygenase pathway. The results of these studies are
      consistent with the hypothesis that (ONOO-) is rapidly converted in the hindlimb
      circulation to a substance that has the properties of an NO donor. These studies
      suggest that under physiologic conditions, the cytotoxic effects of (ONOO-) on a
      short-term basis may have been overemphasized.

PMID- 18049303
TI  - Telmisartan improves endothelial function in patients with essential
      hypertension.
AB  - BACKGROUND: : Hypertension is a cardiovascular risk factor commonly associated
      with endothelial dysfunction and increased renal vascular resistance. Angiotensin
      receptor blockers (ARBs) may beneficially affect these parameters via antagonism
      of angiotensin type 1 (AT1) receptor-mediated vasoconstriction and vascular
      superoxide production. We therefore investigated whether the new ARB telmisartan
      improves endothelial function and renal vascular resistance in patients with
      essential hypertension. METHODS: : Thirty-seven patients with essential
      hypertension were randomized to receive telmisartan, the calcium channel blocker
      nisoldipine, or their combination for 6 weeks in a prospective, parallel group
      study. Brachial artery flow-mediated (endothelium-dependent) dilation (FMD) and
      renal vascular resistance index (RVRI) were evaluated using high-resolution
      ultrasound before, at 3 weeks (low dose), and at 6 weeks (high dose) after
      initiation of treatment. RESULTS: : At baseline, FMD and RVRI did not
      significantly differ between treatment groups. After 3 weeks of treatment neither
      treatment significantly changed FMD or RVRI. After 6 weeks of treatment, patients
      randomized to receive telmisartan alone or the combination, but not those treated
      with nisoldipine alone, displayed a significantly improved FMD, whereas RVRI
      values again were not significantly different as compared to those at baseline.
      CONCLUSION: : In our study cohort of patients with essential hypertension,
      treatment with telmisartan improved FMD but did not change RVRI. Future studies
      will demonstrate whether this telmisartan-induced effect may contribute to a
      blood pressure-independent reduction in cardiovascular morbidity.

PMID- 18049304
TI  - Angiotensin II type 2 receptor vasoactivity in internal mammary arteries of
      patients with coronary artery disease.
AB  - BACKGROUND: Several animal studies suggested that the angiotensin II type 2 (AT2)
      receptor subtype mediates vasodilation, yet the results in human arteries are
      less well described and more inconsistent. Therefore, we evaluated the role of
      the AT2 receptor stimulation on the vasotonus of human internal mammary arteries.
      METHODS: Internal mammary arteries were obtained from 50 patients undergoing
      coronary bypass surgery. The expression of angiotensin II type 1 (AT1) receptor
      and AT2 receptor mRNA was determined by using real-time polymerase chain
      reaction. In addition, angiotensin II and CGP42112A concentration-response curves
      (concentration range: 10(-10) M to 10(-6) M) were constructed in absence or
      presence of candesartan (10(-5) M) and/or the AT2 receptor-antagonist PD-123319
      (10(-6) M) and/or the alpha receptor antagonist phentolamine. RESULTS: Both AT1
      and AT2 receptor protein and mRNA were detected, and higher AT2 receptor mRNA
      expression levels were associated with increased contractile response to
      angiotensin II. Angiotensin II caused vasoconstriction up to 41.1 +/- 6.5% of the
      maximal response to phenylephrine, and PD123319 significantly reduced this
      response (28.6 +/- 9.6%, P < 0.001). Candesartan completely blocked the
      angiotensin II-mediated response (1.4 +/- 3.1%, P < 0.001 versus control), and
      additional blockade of the AT2 receptor with PD123319 did not change this effect
      (1.8 +/- 5.1%). Phentolamine (10(-5) M) caused attenuation and rightward shift of
      the angiotensin II concentration response curves. The AT2 receptor agonist
      CGP42112A did not induce a significant response. CONCLUSION: Although AT2
      receptor mRNA is present in human internal mammary arteries, AT2 receptor
      stimulation does not mediate vasodilation in these arteries.

PMID- 18049305
TI  - Tamoxifen stimulates calcium entry into human platelets.
AB  - The anti-estrogenic drug tamoxifen, which is used therapeutically for treatment
      and prevention of breast cancer, can lead to the development of thrombosis. We
      found that tamoxifen rapidly increased intracellular free calcium [Ca2+]i in
      human platelets from both male and female donors. Thus 10 microM tamoxifen
      increased [Ca2+]i above the resting level by 197 +/- 19%. Tamoxifen acted
      synergistically with thrombin, ADP, and vasopressin to increase [Ca2+]i. The anti
      estrogen ICI 182780 did not attenuate the effects of tamoxifen to increase
      [Ca2+]i; however, phospholipase C inhibitor U-73122 blocked this effect. 4
      hydroxytamoxifen, a major metabolite of tamoxifen, also increased [Ca2+]i, but
      other tamoxifen metabolites and synthetic derivatives did not. Three hydroxylated
      derivatives of triphenylethylene (corresponding to the hydrophobic core of
      tamoxifen) which are transitional structures between tamoxifen (Ca agonist) and
      diethylstilbestrol (Ca antagonist) increased [Ca2+]i slightly (6% to 24%) and
      partially inhibited thrombin-induced [Ca2+]i elevation (68% to 79%). Therefore
      the dimethylaminoethyl moiety is responsible for tamoxifen being a Ca agonist
      rather than antagonist. 4-Hydroxytamoxifen and polymer-conjugated derivatives of
      4-hydroxytamoxifen increased [Ca2+]i, with similar efficacy. The ability of
      tamoxifen to increase [Ca2+]i in platelets, leading to platelet activation, and
      its ability to act synergistically with other platelet agonists may contribute to
      development of tamoxifen-induced thrombosis.

PMID- 18049306
TI  - Adverse balance of nitric oxide/peroxynitrite in the dysfunctional endothelium
      can be reversed by statins.
AB  - Vascular endothelial dysfunction is a complex phenomenon that might be caused by
      a deficiency of nitric oxide (NO) and an overproduction of peroxynitrite (ONOO-).
      This study used a nanotechnological approach to monitor the in vitro effect of
      statins on the [NO]/[ONOO-] balance in normal and dysfunctional endothelial
      cells. NO and (ONOO-) were measured by electrochemical nanosensors in a single
      human umbilical vein endothelial cell (HUVEC) treated with atorvastatin or
      simvastatin for 24 hours in the presence or absence of 50 microg/mL oxidized-LDL.
      An imbalance between [NO]/[ONOO-] concentrations was used as an indicator of
      endothelial dysfunction and correlated with endothelial nitric oxide synthase
      (eNOS) expression. Ox-LDL induced dysfunction of the endothelium by uncoupling
      eNOS. NO concentration decreased from 300 +/- 12 to 146 +/- 8 nmol/L and (ONOO-)
      increased from 200 +/- 9 to 360 +/- 13 nmol/L. The [NO]/[ONOO-] balance decreased
      from 1.50 +/- 0.04 (control) to 0.40 +/- 0.03 for cells co-incubated with ox-LDL.
      Treatment with statins reversed eNOS uncoupling, induced by oxidized-LDL and
      significantly increased the [NO]/[ONOO-] balance to 1.2 +/- 0.1. These results
      demonstrate that statins can restore endothelial function by increasing eNOS
      expression, decreasing eNOS uncoupling, reducing the (ONOO-) level (nitroxidative
      stress), and shifting the [NO]/[ONOO-] balance towards NO.

PMID- 18049307
TI  - Therapeutic concentrations of tacrolimus do not interfere with endothelial nitric
      oxide synthesis in rat thoracic aortas and coronary arteries.
AB  - This study aimed to investigate the potential effect of in vivo administration of
      immunosuppressive agent FK-506 (tacrolimus) on the endothelial function of rat
      thoracic aortas with respect to nitric oxide (NO) synthesis. In vitro effect of
      the drug on NO synthesis in cultured rat coronary microvascular endothelial cells
      (CMEC) was also studied.In vivo administration of tacrolimus (1 mg/kg/d,
      intramuscular) to rats for 14 days resulted in decreased relaxant responses to
      the higher concentrations (1 to 30 muM) of acetylcholine in the aortas; however,
      responses to calcium ionophore A23187, sodium nitroprusside, L-arginine, and L
      NAME did not change significantly. No changes were observed in phenylephrine
      induced contractions in endothelium-denuded or -intact preparations.
      Administration of the vehicle for 14 days did not affect these parameters. In
      order to evaluate the in vitro effect of tacrolimus on NO release, CMEC isolated
      from rat hearts were incubated with either tacrolimus (0.01, 0.1 microM) or the
      vehicle. Basal, calcium ionophore-stimulated, or interleukin-1 beta-induced NO
      synthesis was determined by measuring total nitrite in the media. Neither
      tacrolimus nor the vehicle changed nitrite accumulation. It has been concluded
      that therapeutic concentrations of tacrolimus do not alter NO production in rat
      thoracic aorta or cultured CMEC; however, it impairs relaxant responses of rat
      aorta induced by higher concentrations of acetylcholine, possibly through changes
      in the downstream of receptor activation or through an imbalance between
      endothelium-dependent relaxant and contracting factors within the endothelium in
      favor of the contracting factor(s).

PMID- 18049308
TI  - Pharmacokinetics and pharmacology of hirulog-like peptide.
AB  - Hirulog-like peptide (HLP), a new thrombin peptide inhibitor, effectively reduces
      neointimal formation or restenosis in rat and rabbit vascular injury models. The
      present study investigated the pharmacokinetics and pharmacology of HLP in
      Sprague-Dawley (SD) rats. The input response of HLP in rats was studied using
      radioisotopic tracing method. Male SD rats were intravenously injected with a
      single dose of I-HLP (3.2, 6.4, or 12.8 mg/kg) for pharmacokinetic analysis. The
      concentration-time curve of I-HLP following bolus injection fitted a 3
      compartment model. The half-life of HLP in rats was between 25 and 31 min
      following 3.2 to 12.8 mg/kg of bolus injection. Radioactivity of I-HLP was
      detected in all tested tissues and was most abundant in kidneys or stomachs.
      Blood pressure, respiratory frequency, and heart rates were not significantly
      altered during continuous intravenous infusion with saline or 1.6 to 3.2 mg/kg/h
      of HLP for 4 h. Bleeding time and activated partial thromboplastin time were
      significantly prolonged in rats infused with HLP compared to vehicle. ADP-induced
      platelet aggregation was significantly reduced in the HLP-treated groups compared
      with controls. The results suggest that HLP possesses first-order kinetic
      characteristics. HLP is secreted mainly through kidneys. Beside its anticoagulant
      activity, no other adverse effect was detected in SD rats receiving HLP.

PMID- 18049309
TI  - Effective pharmacotherapy against oxidative injury: alternative utility of an ATP
      sensitive potassium channel opener.
AB  - Cardiomyocyte viability following ischemia-reperfusion critically depends on
      mitochondrial function. In this regard, potassium channel openers (KCOs)
      targeting mitochondria have emerged as powerful cardioprotective agents when
      applied at the onset of ischemia. However, it is controversial whether openers
      are still protective when applied at the onset of reoxygenation. Here, H9c2
      cardiomyocytes and mitochondria isolated from the rat heart ventricle were
      subjected to ischemia-reoxygenation or oxidative stress in the absence or
      presence of 100 microM diazoxide, a potassium channel opener. Ischemia
      reoxygenation or oxidative stress significantly reduced cell viability, induced
      structural damage in association with increased mitochondrial protein release,
      and impaired oxidative phosphorylation. However, treatment with diazoxide before
      anoxia or at the onset of reoxygenation, as well as during oxidative stress,
      prevented cell death and mitochondrial dysfunction and preserved cellular and
      mitochondrial structural integrity. These protective effects were blocked by 5
      hydroxydecanoate. Thus, treatment with potassium channel openers even at the time
      of reoxygenation may provide a significant protection of the myocardium. The
      protective mechanism is at least in part endogenous to the mitochondria because
      protection was also observed in isolated mitochondria.

PMID- 18049310
TI  - Preconditioning with levosimendan prevents contractile dysfunction due to H2O2
      induced oxidative stress in human myocardium.
AB  - We studied the inotropic and possible antioxidant effects of levosimendan in
      human atrial strips, before and after induction of oxidative stress induced by
      H2O2. Levosimendan (10(-9) to 10(-6) M) increased contractions induced by
      electrical stimulation (ES) in human atrial strips. The maximal positive
      inotropic effect of levosimendan was 145.6 +/- 4.6% of predrug values. H2O2 (10(
      6) to 10(-3) M) significantly reduced contractions induced by ES. The maximum
      inhibition by H2O2 on the ES induced contraction was 47.2 +/- 3.5%. Levosimendan
      significantly increased the isometric contractions induced by ES when compared
      with the values obtained in the presence of 10 M H2O2 by 89.0 +/- 4.7%, 98.9 +/-
      3.4%, and 111.2 +/- 3.7% at 10(-8), 10(-7), and 10(-6) M concentrations,
      respectively. In concentrations of 10(-7) and 10(-6) M levosimendan, the maximum
      responses to ES increased when compared with the values obtained in the presence
      of 10(-3) M H2O2 by 87.1 +/- 3.6% and 95.1 +/- 5.3%, respectively. The
      cumulatively applied H2O2 (10(-6)-10(-3) M) did not change the positive inotropic
      response to levosimendan. In conclusion, levosimendan reverses the myocardial
      dysfunction induced by oxidative stress in human right atrial strips.
      Levosimendan prevents myocardial dysfunction if administered before oxidative
      stress.

PMID- 18049311
TI  - Therapeutic effects of autologous bone marrow cells and metabolic intervention in
      the ischemic hindlimb of spontaneously hypertensive rats involve reduced cell
      senescence and CXCR4/Akt/eNOS pathways.
AB  - Peripheral arterial disease (PAD) is a major health problem, especially when
      associated with severe hypertension. Administration of autologous bone marrow
      cells (BMCs) is emerging as a novel intervention to induce neoangiogenesis in
      ischemic limb models and in patients with PAD. This study evaluates the
      neovascularization capacity of BMCs alone or in combination with metabolic
      cotreatment (0.8% vitamin E, 0.05% vitamin C, and 5% of L-arginine) in a rat
      model of ischemic hindlimbs of spontaneously hypertensive rats (SHR) and
      normotensive Wistar-Kyoto rats (WKY). Molecular mechanisms were investigated in
      bone marrow-derived endothelial progenitor cells (BM-EPC) derived from rats. BMC
      therapy increased blood flow and capillary densities and Ki67 proliferative
      marker, and it decreased interstitial fibrosis. These effects were amplified by
      metabolic cotreatment, an intervention that induces vascular protection at least
      partly through the nitric oxide (NO)/endothelial nitric oxide synthase (eNOS)
      pathway, reduction of systemic oxidative stress, and macrophage activation. In
      addition, BMC therapy alone and, more consistently, in combination with metabolic
      treatment, ameliorated BM-EPC functional activity via decreased cellular
      senescence and improved homing capacity by increasing CXCR4-expression levels.
      These data suggest potential therapeutic effects of autologous BMCs and metabolic
      treatment in hypertensive PAD patients.

PMID- 18049312
TI  - Inhibitory effect of GSPE on RAGE expression induced by advanced glycation end
      products in endothelial cells.
AB  - Advanced glycation end products' (AGEs) engagement of a cell-surface receptor for
      AGEs (RAGE) has been causally implicated in the pathogenesis of diabetic vascular
      complications via induction of reactive oxygen species (ROS) and subsequent
      alteration of many gene expressions, including RAGE itself. Grapeseed
      proanthocyanidin extract (GSPE), which is a naturally occurring polyphenolic
      compound, has been reported to possess potent radical-scavenging and antioxidant
      properties and to display significant cardiovascular protective action. In this
      study, we investigated whether GSPE could inhibit AGE-induced RAGE expression
      through interference with ROS generation in human umbilical-vein endothelial
      cells (HUVECs). AGE-modified bovine serum albumin (AGE-BSA) was prepared by
      incubating BSA with high-concentration glucose. Stimulation of cultured HUVECs
      with 200 microg/mL of AGE-BSA significantly enhanced intracellular ROS formation
      and subsequently upregulated the protein and mRNA expression of RAGE; unmodified
      BSA and GSPE alone had no effect. However, GSPE preincubation markedly
      downregulated AGE-induced surface expression of RAGE in a time- and concentration
      dependent manner. In AGE-stimulated HUVECs, GSPE also dose-dependently decreased
      RAGE mRNA levels and inhibited AGE-induced ROS generation at defined time
      periods. These results demonstrate that GSPE can inhibit enhanced RAGE expression
      in AGE-exposed endothelial cells by suppressing ROS generation, thereby limiting
      the AGE-RAGE interaction. Hence, GSPE may have therapeutic potential in the
      prevention and treatment of vascular complications in diabetic patients.

PMID- 18049313
TI  - Role of tyrosine phosphorylation in U46619-induced vasoconstriction of pulmonary
      vasculature and its modulation by genistein, daidzein, and equol.
AB  - We compared the effects of genistein with its structural derivatives daidzein and
      equol on excitation of pulmonary artery and vein. The concentration of genistein
      necessary to inhibit contractions evoked by U46619 (1nM-100 microM) ranged from
      10 to 100 microM. Genistein (55 microM) reduced KCl-responses by approximately
      50% and essentially abolished those evoked by U46619. Daidzein was much less
      effective against either agonist, and equol was ineffective against U46619.
      A23187-evoked contractions were markedly reduced by all 3 isoflavones, but
      caffeine-evoked contractions were not. Using the Western blot technique, we found
      many proteins were tyrosine phosphorylated within 30 seconds after stimulation
      with U46619, reaching a peak at 120 seconds and then falling at 300 seconds. One
      band at 110 kD was increased nearly 300% above baseline, while 3 others ranging
      from 60 to 80 kD were more than doubled in intensity. Genistein had little effect
      on baseline levels of phosphorylation but largely prevented the U46619-induced
      change; daidzein was much less effective in this respect, and equol did not
      significantly affect this phosphorylation. We conclude that these isoflavones
      provide powerful tools in the study of excitation-contraction coupling of
      pulmonary vasculature and that inhibition of tyrosine kinase activity may be
      useful clinically against pulmonary hypertension.

PMID- 18049315
TI  - Comparison of the efficacies of five different statins on inhibition of human
      saphenous vein smooth muscle cell proliferation and invasion.
AB  - Statins (HMG-CoA reductase inhibitors) exhibit beneficial effects on the
      vasculature independently of their cholesterol-lowering properties. These
      pleiotropic effects underlie the ability of statins to reduce intimal hyperplasia
      in saphenous vein (SV) bypass grafts by attenuating smooth muscle cell (SMC)
      invasion and proliferation. Although all statins can effectively lower
      cholesterol, the pleiotropic effects of individual statins may well differ. We
      therefore compared the concentration-dependent effects of 4 lipophilic statins
      (simvastatin, atorvastatin, fluvastatin, and lovastatin) and 1 hydrophilic statin
      (pravastatin) on the proliferation and invasion of SMC cultured from SV of 9
      different patients undergoing coronary artery bypass grafting (CABG). The
      lipophilic statins inhibited SV-SMC proliferation over a 4-day period with an
      order of potency of fluvastatin > atorvastatin > simvastatin > lovastatin (IC50
      range = 0.07 to 1.77 microM). Similarly, these statins also inhibited SV-SMC
      invasion through an artificial basement membrane barrier (fluvastatin >
      atorvastatin > simvastatin >> lovastatin; IC50 range = 0.92 to 26.9 microM). In
      contrast, the hydrophilic pravastatin had no significant effect on SV-SMC
      proliferation at concentrations up to 10 microM, nor did it attenuate SV-SMC
      invasion (up to 30 microM). Our data provide strong evidence that individual
      statins possess differential pleiotropic effects on SV-SMC function. This may be
      of clinical relevance in the selection of individual statins for the treatment of
      CABG patients.

PMID- 18049314
TI  - Redox state of dipyridamole is a critical determinant for its beneficial
      antioxidant and antiinflammatory effects.
AB  - Dipyridamole, a well-known inhibitor of cGMP-dependent phosphodiesterase and the
      adenosine transporter, reportedly possesses antioxidant properties and attenuates
      reactive oxygen species (ROS) formation in platelet and endothelial cells. The
      relevance of the redox status of this compound or the mechanism for its redox
      dependent effects is unknown. Oxidation of dipyridamole by horseradish peroxidase
      and hydrogen peroxide diminished its fluorescence and attenuated dipyridamole
      mediated DPPH and ferric ferrozine reduction. Oxidation also led to elimination
      of dipyridamole's redox-sensitive properties, including inhibiting Cu (II)
      induced LDL oxidation and ROS generation. Attenuation of activation- induced
      platelet release of soluble CD40 ligand (sCD40L) was diminished after
      dipyridamole oxidation. Dipyridamole but not oxidized dipyridamole effectively
      inhibited platelet adhesion to collagen-coated slides under flow conditions. By
      Western blot analysis, dipyridamole enhanced stimulation-induced platelet VASP
      phosphorylation, whereas oxidized dipyridamole caused attenuation. Using
      luciferase assays and nuclear translocation studies with confocal microscopy and
      Western blot analysis, native dipyridamole diminished TNF alpha or thrombin
      induced NF kappa B activation and I kappa B alpha phosphorylation. Oxidized
      dipyridamole had no effect on TNFalpha-mediated NF kappa B activation. These
      results indicate: (1) the redox state of dipyridamole regulates its antioxidant
      properties; (2) dipyridamole's platelet inhibitory effects are manifested by
      enhanced VASP phosphorylation and platelet adhesion on collagen; and (3)
      dipyridamole's antioxidant effects in vascular cells are at least partially
      mediated via suppression of inflammatory NF kappa B signaling.

PMID- 18049316
TI  - Modulating role of alcohol and acetaldehyde on neutrophil and monocyte functions
      in vitro.
AB  - Moderate alcohol intake lowers coronary heart disease risk. Because
      polymorphonuclear neutrophils (PMN) and monocytes (Mo) play a role in
      atherosclerotic plaque destabilization we investigated in vitro effects of
      clinically relevant concentrations of ethanol (0.05, 0.125, 0.25, and 0.5%) and
      its metabolite acetaldehyde (0.0625, 0.125, and 0.5 mM) on human PMN and Mo
      phagocytic functions. PMN and Mo from healthy volunteers were separated and
      purified according standard methods and the following parameters were determined:
      phagocytic activity (percent of phagocytes with at least one ingested particle),
      ingestion index (number of ingested particles per 100 phagocytic cells), and
      intracellular killing (percent of dead ingested particles per 100 phagocytes)
      using acridine orange method and living yeast cells as targets. Reactive oxygen
      species (ROS) formation of ethanol-treated PMN and Mo was evaluated using 2,7
      dichlorofluorescin method and results were expressed as percent of fluorescence
      positive cells. Ethanol and acetaldehyde significantly reduced PMN phagocytic
      functions, with the exception of phagocytic activity, starting at 0.125% for
      ethanol and 0.0625 mM for acetaldehyde. Mo ingestion and microbicidity were
      decreased at ethanol concentrations of 0.5% without effect on Mo phagocytic
      activity. Acetaldehyde impaired Mo ingestion ability starting at 0.0625 mM and
      phagocytic activity at 0.5 mM while was without effect on Mo microbicidity. ROS
      production was significantly increased at ethanol concentrations 0.25 and 0.5% in
      PMN and at 0.5% in Mo. These results might partly explain the beneficial role of
      moderate use of alcohol on cardiovascular disease.

PMID- 18049317
TI  - Racial differences in parental reports of attention-deficit/hyperactivity
      disorder behaviors.
AB  - OBJECTIVE: Accurate assessment of racial disparities in attention
      deficit/hyperactivity disorder (ADHD) depends on measurement that is equally
      valid for all groups. This study examines differences among African American and
      white children in ADHD measurement with a widely used parental report instrument,
      the Diagnostic Interview Schedule for Children (DISC). METHODS: Data come from
      1070 children in the Fast Track Project, a longitudinal study of predominantly
      low-income children at risk of emotional and/or behavioral problems. Item
      Response Theory (IRT) methodology is used to determine whether ADHD screening
      items provide comparable information for African American and white children or
      whether differential item function (DIF) exists. IRT scores and race/ethnicity
      are entered in logistic regression models predicting use of ADHD medication.
      RESULTS: Seven of 39 DISC items performed differently among African Americans and
      whites. In most cases, parents of white children were more likely to endorse
      these items than were parents of African American children at comparable
      underlying levels of children's hyperactivity. When items exhibiting differential
      functioning were deleted, race disparities predicting underlying need as
      indicated by ADHD medication use decreased and were no longer statistically
      significant. CONCLUSIONS: Perceptions of ADHD-related symptoms among parents of
      African American children appear to differ in important ways from those of
      parents of white children, and screening instruments relying on parent report may
      yield different results for African American and white children with similar
      underlying treatment needs. Gathering information from additional sources
      including teachers and school counselors can provide a more complete picture of
      the behavioral functioning and therapeutic needs of children in all race/ethnic
      groups.

PMID- 18049318
TI  - Cerebral blood flow velocity asymmetry, neurobehavioral maturation, and the
      cognitive development of premature infants across the first two years.
AB  - OBJECTIVE: Premature infants are at risk of adverse developmental outcomes even
      with no demonstrable neurological damage. Neonatal physiological measures that
      can serve as indicators of later development are therefore important for early
      evaluation and intervention. METHODS: We followed the development of 51 low birth
      weight, premature infants across the first 2 years. Mean systolic cerebral blood
      flow velocity (CBFV) in the left and right middle cerebral arteries was measured
      at 37 weeks gestational age, neurobehavioral maturation was assessed with the
      Neonatal Behavior Assessment Scales (NBAS), and cognitive development was
      evaluated at 6, 12, and 24 months. RESULTS: Different patterns emerged for CBFV
      in the right versus left middle cerebral artery. Greater absolute values of right
      systolic CBFV were related to poorer performance on the habituation and
      orientation scales of the NBAS, whereas greater left systolic CBFV absolute
      values were related to better Mental Development Index (MDI) scores at 24 months.
      Right systolic CBFV asymmetry was related to poor neonatal orientation and low
      MDI score at 24 months. On the other hand, infants with left systolic CBFV
      asymmetry showed a more rapid increase in cognitive skills from 12 to 24 months
      and better cognitive performance at 2 years. CONCLUSION: Measurement of systolic
      CBFV in the neonatal period may assist in identifying infants at risk of poor
      developmental outcome.

PMID- 18049319
TI  - Psychiatric features and parenting stress profiles of subtypes of attention
      deficit/hyperactivity disorder: results from a clinically referred Taiwanese
      sample.
AB  - OBJECTIVE: This study attempts to evaluate whether there are attention deficit/
      hyperactivity disorder (ADHD) subtype differences regarding psychiatric features,
      comorbidity pattern and parenting stress profiles in an Asian population.
      METHODS: A total of 182 ADHD children and their primary caretakers recruited from
      a university-affiliated hospital were surveyed. Subjects were two groups of
      preadolescent (6 to 12 years old) ADHD children: children with ADHD-inattentive
      subtype (n=58) and ADHD-combined subtype (n=124). Various information was
      collected and compared, including the child's characteristics (current age,
      gender, number of family members, age at ADHD diagnosis, duration of
      pharmaceutical intervention, psychiatric comorbidities, and intelligence
      quotient); the primary caretaker's characteristics, and profiles obtained with
      the Parenting Stress Index (PSI). RESULTS: Group comparison showed that these two
      subtypes were statistically distinguishable from each other in total scores on
      the PSI, four subscale scores on the PSI, the child's age at diagnosis, and
      comorbidity profiles (all p<.05). Parents of children of the combined subtype
      experienced higher parenting stress and felt their children displayed qualities
      that made it difficult for them to fulfill their parenting roles. School failure
      (p=.001) and anxiety disorders (p=.022) were significantly more prevalent in the
      inattentive subtype children, while oppositional defiant disorder was
      significantly more present in the combined subtype children (p=.000).
      CONCLUSIONS: Our findings supported the cross-cultural equivalence of the
      nosological distinction in ADHD subtypes. The need for specific clinical
      intervention according to the subtype difference was stressed.

PMID- 18049320
TI  - Neurocognitive correlates of problem behavior in environmentally at-risk
      adolescents.
AB  - OBJECTIVE: This study prospectively examines the correlation between
      neurocognitive (NC) functioning and problem behavior in early adolescence.
      METHODS: As part of a longitudinal study, African American urban youths of lower
      socioeconomic status, mean age 12.1 years (SD=1.2, n=111), were administered a
      battery of 16 NC tasks assessing eight NC systems (two tasks per system)
      including four systems primarily associated with frontal cortex and four
      primarily associated with nonfrontal cortex. The former systems included (1)
      executive cognitive functioning (ECF), (2) cognitive control, (3) working memory,
      and (4) reward processing. The latter systems included (5) receptive language,
      (6) spatial cognition, (7) visual cognition, and (8) memory. The Teacher's Report
      Form of the Achenbach System of Empirically Based Assessment was performed
      approximately at the same age that the NC assessments were performed. Bivariate
      correlations were calculated between the eight NC system composite scores and the
      externalizing scores. RESULTS: Significant negative relationships were found
      between ECF and receptive language ability and externalizing behavior. Further
      analyses, using linear regression, showed that receptive language was more
      predictive of externalizing behavior than ECF. CONCLUSION: Based on these results
      we conclude that (1) NC functioning, specifically in ECF and in receptive
      language systems, was associated with adolescent problem behavior and (2)
      receptive language was more strongly associated with problem behavior than ECF.

PMID- 18049321
TI  - Examining the effects of maternal chronic illness on child well-being in single
      parent families.
AB  - OBJECTIVE: Chronic illness is highly prevalent among adults with children. It is
      therefore important to understand how parental illness may or may not have an
      impact on affected families. Findings thus far have suggested that differences
      between children with and without a sick parent are minimal, but there are
      individual and familial moderators of outcome. It is unclear whether these
      results are generalizable to single-parent families. The purpose of the present
      study was to examine whether maternal chronic illness affects multiple aspects of
      child functioning in a large, ethnically diverse sample of single-parent families
      compared to those not affected by illness. Potential moderators of differences,
      including maternal distress, parenting variables (aggravation and warmth),
      functional impairment related to illness, and demographic characteristics were
      also tested. METHODS: Using data from the Child Development Study (CDS), 812
      mother-child pairs were studied. Mothers completed measures of child
      internalizing, externalizing, and positive behaviors, while children completed a
      measure of depression. RESULTS: The results indicated that overall there were no
      differences between children with or without a sick mother on the measures of
      well-being. Higher symptom levels among both cohorts were associated with
      maternal distress and aggravation in parenting only. However, children with a
      sick mother were more likely to have a consultation due to emotional
      difficulties. CONCLUSION: Several areas for future work on how illness affects
      single-parent families were identified such as prospectively studying illnesses
      with a variable course and determining which protective factors promote
      resiliency for children in this difficult situation.

PMID- 18049323
TI  - The effect of educational interventions with siblings of hospitalized children.
AB  - OBJECTIVE: Research has demonstrated that siblings of chronically ill children
      can experience significant emotional and behavior changes; however, few studies
      have looked at the specific impact of pediatric hospitalization on the
      nonhospitalized child. Studies also indicate that children who receive age
      appropriate information are better equipped to handle the stress and anxiety
      often associated with hospitalization.This study explored whether siblings of
      hospitalized children who received educational interventions had lower anxiety
      levels compared to siblings who did not receive interventions. METHODS: A pretest
      posttest experimental design was used with 50 subjects, ages 6-17 years,
      recruited from a children's hospital within a university medical center. Subjects
      were matched according to age, sex, and race, with 25 siblings each in the
      experimental and control groups. Siblings assigned to the experimental group
      received interventions from a standardized educational intervention protocol
      developed by the researcher. Interventions focused on teaching the sibling about
      hospitalization, illness or injury, and treatment for the patient, based on
      cognitive stages of development. All interventions were conducted by child life
      specialists on staff at the hospital with extensive training and experience in
      preparation and procedural teaching. RESULTS: Results shows that siblings who
      received educational interventions had significantly lower anxiety levels after
      interventions, compared to siblings who did not receive interventions.
      CONCLUSION: These findings have significant impact on children's health care and
      supporting family needs when a child is hospitalized.

PMID- 18049324
TI  - Interactive music as a treatment for pain and stress in children during
      venipuncture: a randomized prospective study.
AB  - OBJECTIVE: The experience of venipuncture is seen by children as one of the most
      fearful experiences during hospitalization. Children experience anxiety both
      before and during the procedure. Therefore, any intervention aiming to prevent or
      reduce distress should focus on the entire experience of the procedure, including
      waiting, actual preparation, and conclusion. This study was designed to determine
      whether the presence of musicians, who had attended specific training to work in
      medical settings, could reduce distress and pain in children undergoing blood
      tests. METHODS: Our sample population was composed of 108 unpremedicated children
      (4-13 years of age) undergoing blood tests. They were randomly assigned to a
      music group (n=54), in which the child underwent the procedure while interacting
      with the musicians in the presence of a parent or to a control group (n=54), in
      which only the parent provided support to the child during the procedure. The
      distress experienced by the child before, during and after the blood test was
      assessed with the Amended Form of the Observation Scale of Behavioral Distress,
      and pain experience with FACES scale (Wong Baker Scale) only after the
      venipuncture. RESULTS: Our results show that distress and pain intensity was
      significantly lower (p<.001; p<.05) in the music group compared with the control
      group before, during, and after blood sampling. CONCLUSIONS: This controlled
      study demonstrates that songs and music, performed by "professional" musicians,
      have a beneficial effect in reducing distress before, during, and after blood
      tests. This study shows, moreover, that the presence of musicians has a minor,
      but yet significant, effect on pain due to needle insertion.

PMID- 18049325
TI  - The struggle to assure equal treatment for all children with ADHD.
AB  - This commentary considers the impact of applying IRT to a parent-report measure
      of ADHD for the purposes of reducing racial disparities in the instrument's
      performance. It dwells on the difficulties of assessing complex, dynamic
      conditions such as ADHD and the particular problems presented by cultural
      variations in how the condition presents itself and informants view the behaviors
      tied to it.

PMID- 18049326
TI  - Disruptive and oppositional behavior in an 11-year old boy.

PMID- 18049327
TI  - Biological systems and the development of self-regulation: integrating behavior,
      genetics, and psychophysiology.
AB  - Self-regulation is the ability to control inner states or responses with respect
      to thoughts, emotions, attention, and performance. As such, it is a critical
      aspect of development and fundamental to personality and behavioral adjustment.
      In this review, we focus on attentional, cognitive, and emotional control as we
      discuss the genetic mechanisms and brain mechanisms that contribute to individual
      differences in self-regulation. We conclude with a discussion of the implications
      for deviations in the development of this complex construct and suggestions for
      future research.

PMID- 18049330
TI  - In vivo vaccination with tumor cell lysate plus CpG oligodeoxynucleotides
      eradicates murine glioblastoma.
AB  - Dendritic cell (DC) vaccines have shown antitumor activity in experimental glioma
      models and in human glioma patients. The typical approach has been to generate
      the vaccine ex vivo, by pulsing DCs with tumor lysate or peptides, then
      administering the DCs back into the patient. This process requires significant
      expertise and expenses in DC generation. Immature DCs which present antigens to T
      cells in the absence of appropriate costimulatory signals can lead to induction
      of immune tolerance. Recent studies have shown that coadministration of toll-like
      receptor 9 agonists, CpG oligodeoxynucleotides, can promote DC vaccines to break
      immune tolerance to tumor antigens. We investigated the therapeutic efficacy of
      in vivo DC activation, by directly administering glioma cell lysate with CpG
      oligodeoxynucleotides (CpG/lysate), in glioma-bearing mice. Subcutaneous
      vaccination with CpG/lysate induced a significant increase (P<0.05) in the number
      of total T cells and activated DCs in lymph nodes draining the vaccination site
      as compared to mice treated with CpG or tumor lysate alone. Mice vaccinated with
      CpG/lysate exhibited over 2 times greater median survival than mice in the
      control groups (P<0.05). Up to 55% of mice vaccinated with CpG/lysate were
      rendered tumor-free as assessed by survival and bioluminescent imaging.
      Splenocytes taken from mice vaccinated with CpG/lysate elaborated significantly
      more IFN-gamma production and displayed greater tumor cell lysis activity
      compared with the control groups (P<0.05). These results suggest direct
      vaccination with CpG/lysate provides an alternative and effective approach to
      induce host antitumor immunity and warrants clinical investigation in the
      immunotherapy of cancer.

PMID- 18049331
TI  - Strictly target cell-dependent activation of T cells by bispecific single-chain
      antibody constructs of the BiTE class.
AB  - Bispecific antibodies have been extensively studied in vitro and in vivo for
      their use in redirected tumor cell lysis. A particular challenge of bispecific
      antibody constructs that recognize the invariant CD3 signaling complex is a
      controlled polyclonal activation of T cells that, ideally, is exquisitely
      dependent on the presence of target cells. Otherwise, overt production of
      inflammatory cytokines and secondary reactions may occur as side effects, as can
      be observed with constitutively T-cell activating monoclonal antibodies to CD3 or
      CD28, and with bispecific antibodies bearing Fc gamma portions. Here we analyzed
      2 distinct bispecific single-chain antibody constructs of the BiTE class, called
      MT110 and MT103 (or MEDI-538), for conditional T-cell activation. In the presence
      of target-expressing cell lines, low picomolar concentrations of the BiTE
      molecules were sufficient to stimulate a high percentage of peripheral human T
      cells to express cytokines and surface activation markers, enter into cell cycle,
      and induce redirected lysis of target cells. However, in the absence of target
      cells, the 2 BiTE molecules even at high concentrations did not detectably
      activate T cells. Our data show that T cell activation by monomeric forms of
      MT110 and MT103 is highly conditional in that it is strictly dependent on the
      presence of cells expressing the proper target antigen. BiTE molecules therefore
      qualify for a highly controlled polyclonal T-cell therapy of cancer.

PMID- 18049332
TI  - Generation of a tumor-specific systemic response after intratumoral injection of
      IL-12 and IL-18-loaded polylactic acid microspheres.
AB  - We evaluated the impact and mechanism of interleukin (IL)-18 alone or in
      combination with IL-12 or tumor necrosis factor-alpha when delivered
      intratumorally via polylactic acid microspheres (PLAMs). C57BL6 mice with
      established B16 melanomas underwent a single intratumoral injection of IL-12,
      tumor necrosis factor-alpha, or IL-18 PLAM, alone or in combination. Tumor
      draining lymph nodes and splenocytes were assessed for specific antitumor
      response by FACS analysis and IFN-gamma release assay and enzyme-linked
      immunosorbent spot. Mice with established pulmonary metastases were killed for
      enumeration of pulmonary metastatic nodules after treatment of the primary tumor.
      Intratumoral treatment with IL-12 in combination with IL-18 led to significant
      tumor suppression compared with either cytokine alone. FACS analysis revealed the
      combination of IL-12 and IL-18 resulted in an increase in the percentage of CD3+
      cells within the tumor draining lymph node, attributable to increases in both
      CD4+ and CD8+ T cells. Both IFN-gamma release assay and enzyme-linked
      immunosorbent spot demonstrated a significant and substantial increase in tumor
      specific response with the combination. Treatment of the primary tumor with IL-12
      and IL-18 PLAM led to a significant decrease in pulmonary metastases and
      improvement in survival compared with either cytokine alone. The systemic effects
      were abrogated after depletion of CD8+ or natural killer cells, but not CD4+
      cells. IL-12 and IL-18, when released intratumorally in a sustained fashion as
      can be accomplished through the use of PLAM, demonstrate both local effects on
      tumor growth and the generation of a tumor-specific response capable of
      eradicating distant disease.

PMID- 18049333
TI  - Generation of EBV-specific T cells for adoptive immunotherapy: a novel protocol
      using formalin-fixed stimulator cells to increase biosafety.
AB  - Adoptive immunotherapy with in vitro generated Epstein-Barr virus (EBV)-specific
      T cells is a safe and effective treatment in patients with EBV-related
      complications after transplantation. More frequent use of EBV-specific T cells is
      held back by their cost and time-intensive generation under good manufacturing
      practice (GMP) conditions. Currently, EBV-specific T cells are produced by
      repetitive stimulation of peripheral blood mononuclear cells with EBV-infected
      lymphoblastoid cell lines (LCLs), a protocol that requires several open GMP
      handling steps. The aim of the present study was to improve T-cell generation
      under GMP conditions. We introduce a novel generation protocol that replaces
      repetitive with short-term LCL stimulation of PMBCs. Vital and formalin-fixed
      LCLs were used to further increase biosafety. Stimulated T cells were selected by
      the clinically approved cytokine secretion assay followed by nonspecific
      expansion. Sufficient numbers of EBV-specific T-cell lines were generated with
      all protocols. Specific recognition and killing of EBV-infected targets was found
      and was independent of the generation protocol applied. The novel protocol based
      on formalin-fixed cells, selection, and expansion reduced open GMP-handling steps
      and increased biosafety. Furthermore, fixation will allow the use of transgenic
      LCLs (eg, with cytomegalovirus or tumor antigens) and thereby facilitate the
      generation of antigen-specific T cells directed against pathogens other than EBV.

PMID- 18049335
TI  - Monocyte-derived IL-10 expression predicts prognosis of stage IV melanoma
      patients.
AB  - There are no standard methods to predict response to treatment or outcome of
      stage IV melanoma. Our previous assessment of peripheral blood mononuclear cells
      (PBMC) from immunized patients demonstrated that interleukin (IL)-10 expression
      might be associated with prognosis. However, PBMC are a mixture of CD4+ cells,
      CD8+ cells, and monocytes. This study identified the subset of PBMC responsible
      for IL-10 expression and evaluated the prognostic value of IL-10 expression in
      immunized stage IV patients. Eighty-seven patients with stage IV melanoma were
      randomly selected from our database. All patients had received an allogeneic
      melanoma whole-cell vaccine (Canvaxin) after complete resection of clinical
      disease. Blood samples had been collected serially during Canvaxin administration
      and cryopreserved. Intracellular IL-10 expression was assessed by double staining
      fluorescence-activated cell sorter. CD14+ monocytes are the predominant PBMC
      producing IL-10. Sixteen weeks after treatment (week 16), IL-10 levels were
      significantly (P=0.02) higher in poor-survival patients than those with favorable
      outcomes. Patients were separated into 2 groups on the basis of the CD14+
      monocyte IL-10 response: either increasing or decreasing IL-10 expression from
      preimmunization (week 0) to week 16 blood draws. Patients with increasing IL-10
      levels had significantly shorter survival than those whose IL-10 levels decreased
      at week 16 (P<0.0001). Multivariate analysis demonstrated that trends in IL-10
      levels inversely correlated with survival (P<0.0001). We conclude that CD14+
      monocytes are the dominant cellular source of IL-10 among PBMC and that changes
      in IL-10 expression may serve as an immunologic-based surrogate for predicting
      outcome for stage IV patients after surgical resection.

PMID- 18049334
TI  - Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell
      cancer associated with enteritis and hypophysitis.
AB  - The inhibitory receptor CTLA4 has a key role in peripheral tolerance of T cells
      for both normal and tumor-associated antigens. Murine experiments suggested that
      blockade of CTLA4 might have antitumor activity and a clinical experience with
      the blocking antibody ipilimumab in patients with metastatic melanoma did show
      durable tumor regressions in some patients. Therefore, a phase II study of
      ipilimumab was conducted in patients with metastatic renal cell cancer with a
      primary end point of response by Response Evaluation Criteria in Solid Tumors
      (RECIST) criteria. Two sequential cohorts received either 3 mg/kg followed by 1
      mg/kg or all doses at 3 mg/kg every 3 weeks (with no intention of comparing
      cohort response rates). Major toxicities were enteritis and endocrine
      deficiencies of presumed autoimmune origin. One of 21 patients receiving the
      lower dose had a partial response. Five of 40 patients at the higher dose had
      partial responses (95% confidence interval for cohort response rate 4% to 27%)
      and responses were seen in patients who had previously not responded to IL-2.
      Thirty-three percent of patients experienced a grade III or IV immune-mediated
      toxicity. There was a highly significant association between autoimmune events
      (AEs) and tumor regression (response rate=30% with AE, 0% without AE). CTLA4
      blockade with ipilimumab induces cancer regression in some patients with
      metastatic clear cell renal cancer, even if they have not responded to other
      immunotherapies. These regressions are highly associated with other immune
      mediated events of presumed autoimmune origin by mechanisms as yet undefined.

PMID- 18049336
TI  - Phase I/II trial of outpatient PEG-interferon with interleukin-2 in advanced
      renal cell carcinoma: a cytokine working group study.
AB  - A phase I/II trial was undertaken to determine the maximum tolerated dose of
      polyethylene glycol interferon-alpha-2b (PEG-IFN) with interleukin-2 (IL-2), and
      to evaluate the efficacy and toxicity in patients with metastatic renal cell
      carcinoma. Patients initially received subcutaneous PEG-IFN, 3.0 mcg/kg/wk,
      combined with IL-2, but owing to unexpected toxicity a revised phase I schedule
      ensued. Patients received 1.0, 1.5, 2.0, or 3.0 mcg/kg/wk of PEG-IFN on days 1,
      8, 15, and 22; subcutaneous IL-2 was given at a dose of 5 x 10 IU/m2 every 8
      hours x 3 on day 1, followed daily at 5 x 10 IU/m2 days 2, 3, 4, and 5 of week 1,
      then 5 times per week for 3 weeks, followed by 2 weeks off. The maximum tolerated
      dose of PEG-IFN was 2.0 mcg/kg/wk. Fifty-four patients were enrolled. Frequent
      grade III/IV cardiac and neurologic toxicities led to an expanded phase I trial.
      Eleven serious events in 33 patients in the phase II portion led to early
      termination. No patient died from treatment. The overall response rate in 53
      evaluable patients was 30.2% (95% confidence interval 20.5-39.9), with 2 complete
      responses and 14 partial responses and at least 1 response at each dose level.
      The median duration of response was 11 months (range, 2 to 65+ mo); median
      survival was 20 months (range, 2 to 71+ mo); median time to progression was 4
      months. Despite clinical efficacy, the study was closed prematurely owing to
      excess toxicity. Although all serious adverse events resolved, this degree of
      toxicity is unacceptable for an outpatient treatment regimen.

PMID- 18049337
TI  - Immunization with a recombinant MAGE-A3 protein after high-dose therapy for
      myeloma.
AB  - MAGE-A3 is frequently expressed in high-risk multiple myeloma (MM). We immunized
      a healthy donor with MAGE-A3 protein formulated in AS02B to transfer immunity to
      her identical twin, diagnosed with MAGE-A3-positive MM. After a melphalan 200
      mg/m syngeneic peripheral blood stem cell transplant, primed donor cells
      collected after immunizations were transferred and followed by repeated patient
      immunizations. MAGE-A3 immunizations were well tolerated. Strong MAGE-A3-specific
      antibody, cytotoxic T-lymphocyte (CTL), and T-helper responses were induced in
      both twins. A humoral response was transferred to the patient with the donor
      peripheral blood stem cells and increased by booster immunization. The CTL
      response targeted a previously undescribed HLA-A*6801 binding MAGE-A3115-123
      peptide. MAGE-A3115-123 CTLs were detected in the patient more than 1 year after
      the last immunization. Multiple T-helper cellular responses were detected with
      the dominant response to an HLA-DR11 restricted MAGE-A3 epitope. The patient
      remains in remission 2.5 years after the second transplant. This report shows for
      the first time that immunization of a healthy donor with a defined cancer-testis
      protein induces immune responses that can be transferred and expanded
      posttransplant in the recipient. MAGE-A3 immunization may be a useful adjunct to
      high dose melphalan-based peripheral blood stem cell transplant, providing a new
      therapeutic option for high-risk MM.

PMID- 18049339
TI  - Language access and Latino health care disparities.

PMID- 18049340
TI  - National trends in ethnic disparities in mental health care.
AB  - OBJECTIVE: To compare trends in office-based treatment of mental disorders
      between Hispanics and non-Hispanics. DESIGN, SETTING, AND PARTICIPANTS: Analysis
      of a nationally representative sample of visits to office-based physicians
      conducted between 1993 and 2002 (N = 251,905). Visits were grouped into 3
      discrete time periods, 1993-1996, 1997-1999 and 2000-2002. MAIN OUTCOME MEASURES:
      Rate of diagnosis, type of mental health visit, type of treatment received
      (medication or psychotherapy), rate of psychotropic medications prescription, and
      specialty of the treating physician. RESULTS: From 1993-1996 to 2000-2002, the
      proportion of office visits in which mental health care was provided decreased
      for Hispanics from 12.2% to 11.7% while it increased from 13.1% to 15.7% for non
      Hispanics (P < 0.05). Visits with a diagnosis of mental disorder decreased from
      5.2% to 5.1% in Hispanics but increased from 6.0% to 8.8% in non-Hispanics (P <
      0.05). Visits resulting in prescription of a psychotropic medication decreased
      from 10.2% to 9.3% in Hispanics, while they increased from 10.2% to 12.5% in non
      Hispanics (P < 0.05). Psychotherapy visits decreased from 2.4% to 1.3% in
      Hispanics (P < 0.05), whereas they remained constant (2.5%) in non-Hispanics.
      Visits to a psychiatrist decreased from 2.5% to 1.3% in Hispanics (P < 0.05),
      while they increased (nonsignificantly) from 3.1% to 3.5% for non-Hispanics. Most
      differences persisted after adjusting for age and insurance status. CONCLUSIONS:
      From 1993 to 2002, there was an increase in mental health care disparities
      between Hispanics and non-Hispanics treated by office-based physicians.
      Improvement of the mental health care for Hispanics continues to be an important
      public health priority, with clear opportunities and challenges for health care
      policy-makers and practitioners.

PMID- 18049341
TI  - Association between language proficiency and the quality of primary care among a
      national sample of insured Latinos.
AB  - BACKGROUND: Latinos experience substantial barriers to primary care. Limited
      English language proficiency may be a mechanism for these deficiencies, even for
      Latinos with health coverage. OBJECTIVE: To determine the relationship between
      English language proficiency and the experience of primary care reported by
      insured Latinos. DESIGN, SETTING, PARTICIPANTS: Analysis of the National Latino
      and Asian American Study, a nationally representative household survey, 2002
      2003. This analysis was restricted to Latinos who reported current health
      insurance (n= 1792), and included information on ethnic subgroups. MAIN OUTCOME
      MEASURES: Four outcomes addressed different aspects of the quality of primary
      care: (1) not having a regular source of care or lacking continuity of care, (2)
      difficulty getting an appointment over the phone, (3) long waits in the waiting
      room, and (4) difficulty getting information or advice by phone. RESULTS: English
      language proficiency was associated with the experience of primary care for 3 of
      the 4 outcomes. Insured Latinos with poor/fair English language proficiency were
      more likely than those with good/excellent proficiency to report not having a
      regular source of care or lacking continuity [odds ratio (OR) 2.20, 95%
      confidence interval (CI) 1.60-3.02], long waits (OR, 1.88; CI, 1.34-2.64), and
      difficulty getting information/advice by phone (OR, 1.76; 95% CI, 1.25-2.46).
      CONCLUSIONS: Among insured Latinos, low English language proficiency is
      associated with worse reports of the quality of primary care. These results
      suggest that interventions to address limited English proficiency may be
      important to improving the quality of primary care for this rapidly growing
      population.

PMID- 18049342
TI  - Development and validation of a short-form, rapid estimate of adult literacy in
      medicine.
AB  - BACKGROUND: Although prior studies used the 66-item Rapid Estimate of Adult
      Literacy in Medicine (REALM instrument) for literacy assessment, researchers may
      require a shorter, validated instrument when designing interventions for clinical
      contexts. OBJECTIVE: To develop and validate a very brief literacy assessment
      tool, the REALM-Short Form (REALM-SF). PATIENTS: The model development,
      validation, and field testing validation samples included 1336, 164, and 50
      patients, respectively. SETTING: General medicine and subspecialty clinics and
      medicine inpatient wards. DESIGN: For development and validation samples,
      indicator variables for REALM instrument items were evaluated as potential
      predictors of REALM instrument score by stepwise multiple regression analysis
      with subsequent bootstrap and confirmatory factor analysis of selected items.
      Pearson correlations compared REALM-SF and REALM instrument scores and kappa
      analyses compared grade level assignments. For the field testing validation
      sample, Pearson correlations compared Wide Range Achievement Test and REALM-SF
      scores. RESULTS: The REALM-SF included 7 items with stable model coefficients and
      1 underlying linear factor. REALM-SF and REALM instrument scores were highly
      correlated in development (r = 0.95, P < 0.001) and validation (r = 0.94, P <
      0.001) samples. There was excellent agreement between REALM-SF and REALM
      instrument grade-level assignments when dichotomized at the 6th grade
      (development: 97% agreement, K = 0.88, P < 0.001; validation: 88% agreement, K =
      0.75, P < 0.001) and 8th grade levels (development: 94% agreement, K = 0.78, P <
      0.001; validation: 84% agreement, K = 0.67, P < 0.001). REALM-SF and Wide Range
      Achievement Test scores were highly correlated (r = 0.83, P < 0.001) in field
      testing validation. CONCLUSIONS: The REALM-SF provides researchers a brief,
      validated instrument for assessing patient literacy in diverse research settings.

PMID- 18049343
TI  - Attitudes toward health care providers, collecting information about patients'
      race, ethnicity, and language.
AB  - BACKGROUND: Experts recommend that health care providers (HCPs) collect patients'
      race/ethnicity and language, but we know little about public attitudes towards
      this. OBJECTIVES: To determine attitudes towards HCPs collecting race/ethnicity
      and language data. PARTICIPANTS: A telephone survey was held with 563
      Californians, including 105 whites, 97 blacks, 199 Hispanics (162 Spanish
      speaking), 129 Asians (73 Chinese-speaking), and 33 multiracial individuals.
      MEASURES: Attitudes towards HCPs asking patients their race/ethnicity and
      preferred language, concerns about providing their own information, reactions to
      statements explaining the rationale for data collection, and attitudes towards
      possible policies. RESULTS: Most (87.8%) somewhat or strongly agreed that HCPs
      should collect race/ethnicity information and use this to monitor disparities,
      and 73.6% supported state legislation requiring this. Support for collection of
      patients' preferred language was even higher. However, 17.2% were uncomfortable
      (score 1-4 on 10-point scale) reporting their own race/ethnicity, and 46.3% of
      participants were somewhat or very worried that providing information could be
      used to discriminate against them. In addition, 35.9% of Hispanics were
      uncomfortable reporting their English proficiency. All statements explaining the
      rationale for data collection modestly increased participants' comfort level; the
      statement that this would be used for staff training increased comfort the most.
      CONCLUSIONS: Although most surveyed believe that HCPs should collect information
      about race/ethnicity and language, many feel uncomfortable giving this
      information and worry it could be misused. Statements explaining the rationale
      for collecting data may assuage concerns, but community engagement and
      legislation to prevent misuse may be needed to gain more widespread trust and
      comfort.

PMID- 18049344
TI  - Ethnicity/race and outcome in the treatment of depression: results from STAR*D.
AB  - OBJECTIVES: This secondary analysis of data from the Sequenced Treatment
      Alternatives to Relieve Depression (STAR*D) study compared rates of remission and
      response for blacks (n = 495), whites (n = 1853), and Hispanics (n = 327) with
      nonpsychotic major depressive disorder who were treated with citalopram. METHODS:
      STAR*D included representative outpatients treated in 23 psychiatric and 18
      primary care centers. Participants received flexible doses of citalopram for up
      to 14 weeks, with dosage adjustments based on routine clinical assessments.
      Efforts were made to achieve remission, using a measurement-based care approach
      with adjustments based on symptoms and side effects assessed at each visit.
      RESULTS: There were significant differences among groups on many baseline
      demographic, sociocultural, and clinical variables. Blacks and Hispanics were
      more socially disadvantaged and had more comorbidity than whites. Before
      adjusting for differences, blacks had lower remission rates than whites, with
      Hispanics intermediate between the 2. After adjustments, remission rates for
      groups were not significantly different on the 17-item Hamilton Rating Scale for
      Depression (HRSD), but remained lower for blacks compared with whites with the 16
      item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR). Blacks
      took longer to achieve remission or response, though this did not remain after
      adjusting for baseline differences. CONCLUSIONS: Overall, black and to a lesser
      extent Hispanic participants had a poorer response to citalopram. After adjusting
      for baseline differences, the remission rates seemed to be more similar on the
      HRSD, but remained worse for blacks on the QIDS-SR. We discuss the possible
      biologic and sociocultural factors that may underlie these findings.

PMID- 18049345
TI  - The cumulative effects of quality improvement for depression on outcome
      disparities over 9 years: results from a randomized, controlled group-level
      trial.
AB  - BACKGROUND: Quality improvement (QI) programs for depression can improve outcomes
      of care and reduce outcome disparities; but cumulative effects on mental health
      outcome disparities have seldom been evaluated. OBJECTIVE: To estimate cumulative
      effects over many years of short-term QI programs for depression in primary care
      on mental health outcome disparities, and to develop an interpretation for
      annualized, cumulative mental health outcome scores. DESIGN: : We conducted a
      group-level, randomized controlled trial in 6 US healthcare organizations. The QI
      programs supported provider and patient education in depression treatment and
      resources for medication management (QI-Meds) or access to evidence-based
      psychotherapy (QI-Therapy). Sites were selected to oversample minorities.
      PATIENTS: Results were extrapolated to 1188 initially enrolled and living
      patients depressed at baseline. MAIN OUTCOME: Psychologic well-being (MHI-5)
      estimated as cumulative outcomes and outcome disparities (minority-whites) over 9
      years, and annualized. RESULTS: Across analyses there was a significant
      interaction of intervention status and ethnicity [lowest F(2,160) = 4.96, P =
      0.008]. QI-therapy improved cumulative outcomes among minorities (mean, 37.92
      44.29 MHI-5 points) and reduced outcome disparities for the whole sample relative
      to usual care (UC) (by mean, 39.44-59.01 MHI-5 points) and relative to QI-Meds
      (by mean, 53.90-74.41 MHI-5 points), lowest t(103) = 3.12, P = 0.002. By
      comparison, UC patients who lost a loved one in the year after baseline had lower
      psychologic well being by 6.18 MHI-5 scale points compared with similar UC
      patients without such a loss [t(15)=2.52, P = 0.02]. CONCLUSIONS: QI programs
      incorporating support for evidence-based psychotherapy offer an approach to
      substantially reduce cumulative outcome disparities for depressed primary care
      patients.

PMID- 18049346
TI  - Identification and treatment of mental and substance use conditions: health plans
      strategies.
AB  - BACKGROUND: Mental health and substance use conditions are under-recognized and
      under-treated. Private health plans may be able to affect the extent of screening
      and, thus, identification of enrollees who need treatment. OBJECTIVES: The goals
      of this study were to determine strategies used by health plans to identify
      mental health and substance use conditions; and describe the characteristics of
      health plans associated with use of these strategies. METHODS: In 2003, we
      conducted a nationally representative survey of private health plans regarding
      behavioral health services. A total of 368 health plans (83% response rate)
      provided information about their managed care products: health maintenance
      organization (HMO), point-of-service (POS), or preferred provider organization
      (PPO) products (812 in total). MEASURES: We asked whether plans verify primary
      care providers' screening for mental health or substance use conditions, screen
      outside of primary care, and distribute practice guidelines. We characterized
      each product in terms of "carve-out" to a specialty behavioral health vendor, tax
      status, and region and market area population. RESULTS: Thirty-four percent of
      products verify primary care providers' screening for mental health, but only 8%
      verify alcohol or drug screening. Outside of primary care, 31% conduct screening
      through the mail, phone, or internet. Depression guidelines are distributed to
      primary care providers by 78% of managed care products: alcohol or drug
      guidelines are distributed by 33%. In multivariate analyses, specialty
      contracting was positively associated, and PPO product type was negatively
      associated with these strategies. CONCLUSIONS: Most health plans use multiple
      strategies to improve identification of behavioral health conditions, but use of
      such strategies was greater for mental health than for substance use conditions.

PMID- 18049347
TI  - Explaining racial and ethnic differences in children's use of stimulant
      medications.
AB  - OBJECTIVES: To document and explain racial/ethnic differences in the use of
      stimulant drugs among US children. DATA AND METHODS: We use a nationally
      representative sample of children ages 5-17 years old from the Medical
      Expenditure Panel Survey (MEPS) for the years 2000-2002. We estimate race
      specific means and regressions to highlight differences across groups in
      individual/family characteristics that may affect stimulant use and differences
      in responses to these characteristics. Then, we use Oaxaca-Blinder decomposition
      methods to quantify the portion of differential use explained by differences in
      individual/family characteristics. Finally, we use pooled regressions with
      race/ethnicity interactions to formally test the hypothesis that responses to
      perceived mental health and behavioral problems vary across groups. RESULTS:
      White children are about twice as likely to use stimulants as either Hispanic or
      Black children. Differences in individual/family characteristics account for
      about 25% of the difference between whites and Hispanics, but for none of the
      difference between whites and blacks. Pooled regressions show that racial/ethnic
      gaps in stimulant use persist among children with otherwise similar reported
      mental health conditions. CONCLUSIONS: Our finding that the majority of
      racial/ethnic differences in children's stimulant use is explained by differences
      in responses to individual/family characteristics highlights the importance of
      further research to examine the reasons for these differences. It is striking
      that children with otherwise similar reports of mental health problems have such
      different outcomes in terms of stimulant use. Potential explanations range from
      discrimination to cultural differences by race/ethnicity or community.

PMID- 18049348
TI  - Receiving advice about child mental health from a primary care provider: African
      American and Hispanic parent attitudes.
AB  - BACKGROUND: Primary care providers (PCPs) play a critical role in the
      identification and treatment of child and adolescent mental health problems but
      few studies have examined parents' attitudes on receiving advice about child
      mental health from a PCP and whether attitudes are associated with race or
      ethnicity. OBJECTIVE: To determine if race and ethnicity were associated with
      parents' attitudes on receiving advice about child mental health from a PCP.
      SUBJECTS: Data were collected during 773 visits to 54 PCPs in 13 diverse clinics.
      Families were 56.5% white, 33.3% African American, and 10.1% Hispanic. MEASURES:
      The parent reported attitudes associated with receiving advice about child mental
      health from the PCP. The parent completed the Strengths and Difficulties
      Questionnaire to report youth mental health. PCPs completed measures of
      psychosocial orientation, confidence in mental health treatment skills, and the
      accessibility of mental health specialists. RESULTS: Hispanics were more likely
      than Non-Hispanics to agree that PCPs should treat child mental health and were
      more willing to allow their child to receive medications or visit a therapist for
      a mental health problem if recommended by the PCP. African Americans were
      significantly less willing than whites and Hispanics to allow their child to
      receive medication for mental health but did not differ in their willingness to
      visit a therapist. CONCLUSIONS: Race and ethnicity were associated with parents'
      attitudes on receiving advice about child mental health from a PCP. Primary care
      may be a good point of intervention for Hispanic youth with mental health needs.

PMID- 18049349
TI  - Is lower 30-day mortality posthospital admission among blacks unique to the
      Veterans Affairs health care system?
AB  - BACKGROUND: Several studies have reported lower risk-adjusted mortality for
      blacks than whites within the Veterans Affairs (VA) health care system,
      particularly for those age 65 and older. This finding may be a result of the VA's
      integrated health care system, which reduces barriers to care through subsidized
      comprehensive health care services. However, no studies have directly compared
      racial differences in mortality within 30 days of hospitalization between the VA
      and non-VA facilities in the US health care system. OBJECTIVE: To compare risk
      adjusted 30-day mortality for black and white males after hospital admission to
      VA and non-VA hospitals, with separate comparisons for patients younger than age
      65 and those age 65 and older. RESEARCH DESIGN: Retrospective observational study
      using hospital claims data from the national VA system and all non-VA hospitals
      in Pennsylvania and California. SUBJECTS: A total of 369,155 VA and 1,509,891 non
      VA hospitalizations for a principal diagnosis of pneumonia, congestive heart
      failure, gastrointestinal bleeding, hip fracture, stroke, or acute myocardial
      infarction between 1996 and 2001. MEASURES: Mortality within 30 days of hospital
      admission. RESULTS: Among those under age 65, blacks in VA and non-VA hospitals
      had similar odds ratios of 30-day mortality relative to whites for
      gastrointestinal bleeding, hip fracture, stroke, and acute myocardial infarction.
      Among those age 65 and older, blacks in both VA and non-VA hospitals had
      significantly reduced odds of 30-day mortality compared with whites for all
      conditions except pneumonia in the VA. The differences in mortality by race are
      remarkably similar in VA and non-VA settings. CONCLUSIONS: These findings suggest
      that factors associated with better short-term outcomes for blacks are not unique
      to the VA.

PMID- 18049350
TI  - Effect of increased copayments on pharmacy use in the Department of Veterans
      Affairs.
AB  - OBJECTIVES: In February 2002, the Department of Veterans Affairs (VA) raised
      medication copayments from $2 to $7 per 30-day supply of medication for certain
      veteran groups. We examined the impact of the copayment increase on medication
      acquisition from VA. METHODS: This was a retrospective cohort study using data
      from national VA databases from February 2001 through February 2003. We took a
      random sample of over 5% of male VA users in 2001. Of 149,107 veterans sampled,
      19,504 (13%) had copayments for no drugs, 101,410 (68%) had copayments for some
      drugs, and 28,193 (19%) had copayments for all drugs. We used multivariable count
      models to examine changes in the number of 30-day medication supplies after the
      increase. RESULTS: After the copayment increase, veterans subject to copayments
      for all drugs received 8% fewer 30-day supplies of medication annually relative
      to veterans with no copayments (P < 0.001). The effect of the copayment increased
      as the number of different medications veterans received increased. Among
      veterans subject to copayments for all drugs, acquisition of lower-cost drugs
      fell by 36%, higher-cost medications fell by 6%, over-the-counter medications
      fell by 40%, and prescription-only medications fell by 4% relative to veterans
      with no drug copayments. CONCLUSIONS: The number of medications veterans obtained
      from VA decreased after the copayment increase. There were relatively larger
      impacts on veterans with higher medication use and on lower-cost and over-the
      counter medications.

PMID- 18049351
TI  - Are surname telephone oversamples an efficient way to better understand the
      health and healthcare of minority group members?
AB  - OBJECTIVES: Surname oversamples are commonly used in health research to increase
      the number of persons from minority racial and ethnic groups represented in
      general population surveys. This article considers the sample design efficiency
      in the use of Hispanic, Hmong, and Asian surname samples. METHODS: The study uses
      3 state surveys (Alabama, Missouri, and Minnesota) that used surname oversamples
      to increase the proportion of Hispanic, Hmong, or Asian respondents included in
      the studies. We examine whether surname oversamples lead to more completed
      surveys with the targeted minority groups than would have been achieved if
      surname oversamples had not been used. We also assess gains in terms of effective
      sample sizes from the use of surname oversampling. RESULTS: The sensitivities of
      the Hispanic surname list ranged from 46% to 63% across the 3 surveys. The
      sensitivity of the Asian survey was 34%, and the sensitivity of the Hmong was
      38%. Although the use of surname increased the number of targeted minority group
      members in the final study, the increased number had a very minimal impact on the
      effective sample size of the minority populations for the key survey estimates of
      interest in the 3 health surveys. CONCLUSIONS: The use of surname samples
      achieved the goal of having more persons who identify as Hispanic, Hmong, or
      Asian in the final sample. However, the use of surname oversamples is inefficient
      when considering the statistical power gained for minority group estimates.

PMID- 18049352
TI  - Delayed presentation for human immunodeficiency virus (HIV) care among veterans:
      a problem of access or screening?
AB  - BACKGROUND: Despite the effectiveness of antiretroviral therapy, nearly half of
      patients entering human immunodeficiency virus (HIV) care have advanced disease.
      Many attribute this delay to poor access to healthcare. Others argue that delays
      will persist until routine screening is adopted. The Veterans Health
      Administration (VA) is a unique laboratory to examine whether access to
      comprehensive health benefits results in earlier entry into HIV care. METHODS:
      Retrospective observational study of 4368 HIV-positive patients entering HIV care
      during 1998-2002 at VA medical centers nationwide. OUTCOMES OF INTEREST: rates of
      acquired immune deficiency syndrome in year of presentation; duration of VA
      utilization before HIV presentation; presence of "clinical triggers," signaling
      greater risk of HIV infection, before presentation. RESULTS: Fifty-one percent (n
      = 2211) of all patients presented with CD4 counts of < 200 cells/mm. Thirty-nine
      percent (n = 1697) of all patients used other VA services before presentation for
      HIV care, with median duration of 3.6 years (interquartile range 25-75: 2.2-5.1
      year) and 6 physician visits [interquartile range (IQR), 25-75: 2-18 visits]
      between first utilization and HIV presentation. No difference existed in the
      percentage presenting with CD4 counts <200 cells/mm among those with and without
      prior VA healthcare (50% vs. 51%, P = 0.76). Only 13% of those with prior VA
      healthcare demonstrated a clinical trigger before HIV presentation. CONCLUSIONS:
      More than half of veterans entered HIV care with an acquired immune deficiency
      syndrome diagnosis at presentation irrespective of whether they had previously
      established healthcare in the VA. Access to care does not seem to be the primary
      cause of delayed HIV presentation. Widespread HIV screening is needed to improve
      rates of early detection.

PMID- 18049353
TI  - The effect of integrated medical-substance abuse treatment during an acute
      illness on subsequent health services utilization.
AB  - BACKGROUND: The acute care hospital provides a context for engaging difficult to
      reach patients in substance abuse treatment (SAT); however, little is known
      regarding the effects of such engagement on subsequent health services
      utilization. We examined whether a structured day hospital (DH) intervention
      integrating SAT and medical care during an acute medical hospitalization would
      reduce subsequent emergency department (ED) use and rehospitalization compared
      with a control group receiving usual medical care and referral to intensive
      outpatient SAT. METHODS: Between October 2001 and June 2002, we enrolled 390
      hospitalized substance using patients in a nonrandomized clinical trial. Once
      stabilized, patients were assigned to either the DH intervention (n = 63) or
      usual care control group (n = 327). Baseline interview and chart review collected
      data on demographics, substance use, and acute and chronic medical conditions.
      Subsequent chart review collected data on ED, hospital and ambulatory care
      utilization in the 6 months pre-enrollment and 6 months postdischarge. Univariate
      and multiple logistic regression methods were used to assess the independent
      effects of the DH intervention on postdischarge health care utilization. RESULTS:
      Overall 25%, 48%, and 42% reported > or =3 ED episodes, > or =1
      rehospitalization, and > or =1 ambulatory care visit during the postdischarge
      period. Subjects who completed the DH intervention were significantly less likely
      to have > or =3 ED episodes (AOR = 0.27; 95% CI, 0.08-0.89) and more likely to
      have > or =1 ambulatory care visit (AOR = 4.05; 95% CI, 1.44-11.37) than the
      usual care group. No similarly beneficial effects were seen for patients who
      initiated but did not complete the DH intervention. CONCLUSIONS: : A DH model
      that engages acutely ill substance using patients in integrated medical and
      substance abuse treatment can positively influence subsequent health care seeking
      behavior.

PMID- 18049354
TI  - Gender differences in healthcare-seeking behavior for urinary incontinence and
      the impact of socioeconomic status: a study of the Medicare managed care
      population.
AB  - BACKGROUND: Despite the gender difference in etiology, prevalence and management
      of urinary incontinence (UI) among community-living older adults, little is known
      about the effect of gender on their healthcare-seeking behaviors. OBJECTIVE: To
      determine gender differences in professional care seeking, receipt of UI
      treatment, and the impact of age and socioeconomic status. RESEARCH DESIGN:
      National survey of Medicare managed care enrollees in 2003 and 2004. SUBJECTS: A
      total of 28,724 patients who were noninstitutionalized, age 65 and older, and had
      self-reported UI problem in the last 6 months. MEASURES: Whether a patient with
      UI had discussed the problem with a health provider, and whether a patient having
      had such a discussion received treatment. RESULTS: Compared with incontinent men,
      incontinent women were less likely to seek professional help for the UI problem
      [46.2% vs. 55.7%; adjusted odds-ratio (AOR) = 0.65, P < 0.01], but more likely to
      receive treatment (54.8% vs. 51.4%; AOR = 1.12, P < 0.01) after consulting a
      health professional. These gender differences varied by age, education, or annual
      household income level. For incontinent women, the predicted rate of receiving
      treatment decreased with older age, lower education, and lower income level.
      CONCLUSIONS: Community-living older women with UI problem are less likely to seek
      professional help than their male counterparts, but more likely to be treated
      after a health professional is consulted. Patients' socioeconomic status can
      affect physician behavior and ultimately, their receipt of treatment of UI,
      especially for women. Current efforts to promote awareness and quality-of-care of
      UI among older adults should account for gender and other sociodemographic
      factors.

PMID- 18049355
TI  - Down under optometry takes a big leap.

PMID- 18049357
TI  - Bilateral abducens palsies and facial weakness as initial manifestations of a
      Chiari 1 malformation.
AB  - PURPOSE: Chiari I malformations are rare, congenital anomalies involving the
      caudal herniation of the cerebellar tonsils into the upper cervical spinal canal.
      Osseous abnormalities of the skull permit the extension of the hindbrain below
      the foramen magnum and engender syringohydromyelia formation. Neuroophthalmic
      manifestations are not uncommon; nevertheless, this is the first report of
      concomitant bilateral abducens palsies and facial nerve impairment as presenting
      manifestations of a Chiari I malformation. CASE REPORT: A 30-year-old black
      female presented with a recent history of blurred vision and binocular diplopia
      in both left and right gazes. Headaches, dizziness, and orofacial sensorimotor
      impairments were noted in conjunction with the onset of her diplopia. No history
      of surgery, trauma, or systemic illness was elicited. Extraocular motility
      testing confirmed a complete bilateral abduction deficit. Additional cranial
      nerve testing revealed bilateral facial nerve weakness and tactile hypesthesia in
      the perioral region. No taste disturbances were reported. Nuclear magnetic
      resonance imaging studies revealed a Chiari I malformation with a
      syringohydromyelia formation in the vicinity of the patient's sixth cervical
      vertebrae. Foramen magnum decompression surgery was performed. Two months after
      surgery, abduction capacity was restored along with resolution of symptoms of
      perioral numbness and signs of facial weakness. CONCLUSION: Bilateral sixth nerve
      palsies are rare clinical commodities especially when they do not occur in
      isolation. Intracranial neoplams, trauma, subarachnoid hemorrhaging,
      demyelinating disease, and meningeal infarcts have all been shown to induce mixed
      cranial neuropathies. The concomitant bilateral abducens palsy and concomitant
      facial nerve weakness reported in this case represents an atypical and previously
      unreported presentation of a Chiari I malformation.

PMID- 18049358
TI  - Racial differences in macular thickness in healthy eyes.
AB  - PURPOSE: The relationship between race and macular thickness remains unknown.
      This relationship may be important for early and accurate diagnosis of macular
      disease and glaucoma, and may also provide insight into disease mechanisms. In
      this study, we compared macular thickness in healthy eyes of black and white
      subjects using optical coherence tomography (Stratus OCT). METHODS: This study
      used a matched, cross-sectional design. Subjects underwent OCT macular thickness
      map scanning in each eye, four-field, 45-degree digital retinal imaging in each
      eye, and blood pressure measurement. Retinal images were evaluated for absence of
      posterior pole disorders, including macular and optic nerve disease. Retinal
      thickness was evaluated in the central fovea, and in rings placed at 1, 3, and 6
      mm from fixation. RESULTS: Compared with whites (n = 7), blacks (n = 7) had
      significantly thinner total foveal thickness (TFT, retinal thickness in the
      central 1 mm diameter area; OD: p < 0.03; OS: p < 0.02; OU average: p < 0.02),
      and thinner total macular thickness (TMT, retinal thickness in 6mm diameter area
      excluding central foveal thickness; OS: p < 0.02; OU average: p < 0.03). There
      was a trend for central foveal thickness (retinal thickness at fixation) to be
      thinner in blacks than whites (OD: p = 0.12; OS: p = 0.08). There was no
      significant difference in macular thickness between right and left eyes.
      CONCLUSIONS: Retinal thickness as measured by Stratus OCT in the fovea and macula
      is significantly thinner in blacks compared with age-matched whites. Larger
      multiracial prospective studies are needed to confirm these results and to
      evaluate the need for race-specific normative values.

PMID- 18049359
TI  - Estimating variability in placido-based topographic systems.
AB  - PURPOSE: To describe a new software tool for the detailed presentation of corneal
      topography measurements variability by means of color-coded maps. METHODS:
      Software was developed in Visual Basic to analyze and process a series of 10
      consecutive measurements obtained by a topographic system on calibration spheres,
      and individuals with emmetropic, low, high, and irregular astigmatic corneas.
      Corneal surface was segmented into 1200 segments and the coefficient of variance
      of each segment's keratometric dioptric power was used as the measure of
      variability. The results were presented graphically in color-coded maps
      (Variability Maps). Two topographic systems, the TechnoMed C-Scan and the TOMEY
      Topographic Modeling System (TMS-2N), were examined to demonstrate our method.
      RESULTS: Graphic representation of coefficient of variance offered a detailed
      representation of examination variability both in calibration surfaces and human
      corneas. It was easy to recognize an increase in variability, as the irregularity
      of examination surfaces increased. In individuals with high and irregular
      astigmatism, a variability pattern correlated with the pattern of corneal
      topography: steeper corneal areas possessed higher variability values compared
      with flatter areas of the same cornea. Numerical data permitted direct
      comparisons and statistical analysis. CONCLUSIONS: We propose a method that
      permits a detailed evaluation of the variability of corneal topography
      measurements. The representation of the results both graphically and
      quantitatively improves interpretability and facilitates a spatial correlation of
      variability maps with original topography maps. Given the popularity of
      topography based custom refractive ablations of the cornea, it is possible that
      variability maps may assist clinicians in the evaluation of corneal topography
      maps of patients with very irregular corneas, before custom ablation procedures.

PMID- 18049360
TI  - The impact of lipid on contact angle wettability.
AB  - PURPOSE: To analyze the effect of in vitro lipid doping on conventional hydrogel
      (CH) and silicone hydrogel (SH) lens wettability, assessed by sessile drop
      contact angle (CA) measurement. METHODS: Nine contact lens materials, five SHs
      and four CH, were incubated with two different lipid tear solutions (LTS)
      containing cholesterol, cholesteryl oleate, oleic acid, oleic acid methyl ester,
      and triolein. The first LTS was a "low" concentration solution, which was close
      to human values, and the second was a "high" concentration. Lenses were soaked in
      the two LTS types for 2 or 5 days and compared with lenses soaked in phosphate
      buffered saline (PBS) only. After soaking, advancing CAs were measured on a
      customized computerized device using a sessile drop method. RESULTS: Compared
      with PBS, CAs for untreated SHs were unaffected by soaking in the LTS, with
      typical CA values of >95 degrees (p > 0.05). The surface-treated SH materials
      exhibited markedly reduced CAs after lipid exposure, with the high concentration
      LTS reducing the CA to <5 degrees (p < 0.01). The CH materials all exhibited
      lower CAs after soaking, with values typically decreasing to 35 degrees , which
      was significantly lower than that seen with PBS (p < 0.01). CONCLUSION: Exposure
      to lipid may improve the wettability of certain SH and CH materials, particularly
      those SH materials that are surface treated. This may help to explain why certain
      SH materials appear to improve in comfort for some patients during the first few
      hours or days of wear.

PMID- 18049361
TI  - Biocompatibility and light transmission of liposomal lenses.
AB  - PURPOSE: To validate the biocompatibility and transmittance properties of contact
      lenses bearing intact liposomes. These liposomal lenses loaded with therapeutics
      can be used as ophthalmic drug delivery systems. METHODS: The biocompatibility of
      soft contact lenses, coated with liposomes was evaluated through in vitro direct
      and indirect cytocompatibility assays on human corneal epithelial cells, on
      reconstructed human corneas and on ex vivo rabbit corneas. The direct and
      indirect transmission spectra of liposome-covered lenses were also evaluated to
      test if they transmit all wavelengths of the ultraviolet-visible spectrum, to
      thereby fulfill their optical function, without gross alteration of the colors
      perception and with a minimum of light dispersion. RESULTS: Contact lenses
      bearing layers of stable liposomes did not induce any significant changes in cell
      viability and in cell growth, compared with lenses bearing no liposome. Elution
      assays revealed that no cytotoxic compound leaks from the lenses whether bearing
      liposomes or not. Histological analyses of reconstructed human corneas and ex
      vivo rabbit corneas directly exposed to liposomal lenses revealed neither
      alteration to the cell nor to the tissue structures. Contact lenses bearing
      layers of liposomes did not significantly affect light transmission compared with
      control lenses without liposome at the wavelength of maximal photopic
      sensitivity, i.e., 550 nm. In addition, the contact lenses afford more eye
      protection in the ultraviolet spectrum, compared with the control lenses.
      CONCLUSIONS: Liposomal contact lenses are biocompatible and their transmittance
      properties are not affected in the visible light range.

PMID- 18049362
TI  - Visual acuity with spherical and toric soft contact lenses in low- to moderate
      astigmatic eyes.
AB  - PURPOSE: To evaluate the visual acuity of myopic, astigmatic eyes, with spherical
      and toric soft contact lenses. METHODS: A randomized, masked, cross-over study
      was conducted to compare acuity with soft spherical and toric contact lenses on
      patients with between -0.75 and -2.00 D of refractive astigmatism. A total of 15
      patients (30 eyes) were fitted with four brands of spherical and toric lenses
      (Acuvue Advance, Biomedics 55, Frequency 55, and SofLens 66), in random order. An
      initial visit was conducted to fit the lenses and an over-refraction (OR) was
      performed to determine the best prescription. At the measurement visit, patients'
      pupils were dilated with 1.0% tropicamide and 2.5% phenylephrine to allow
      wavefront aberration measurements, and a final OR was performed. A 6-mm aperture
      was held in front of the eye to measure visual acuity through just the contact
      lens and the contact lens with the final OR. Acuity was measured monocularly,
      under photopic and mesopic conditions with high- and low-contrast logMAR charts
      at distance. Differences in acuity were analyzed using repeated measures analysis
      of variance. RESULTS: Visual acuity with soft spherical contact lenses was not
      significantly different between lens brands. For toric contact lenses, acuity was
      significantly better with Biomedics 55 and SofLens 66 than with Acuvue Advance;
      and acuity with SofLens 66 was significantly better than with Frequency 55. Low
      astigmatic eyes gained between 3 and 5.5 letters of acuity with toric contact
      lenses vs. spherical lenses; and moderate-astigmatic eyes gained between 8 and
      12.5 letters. CONCLUSIONS: Both low- and moderate-astigmatic eyes showed
      improvements in acuity with toric contact lenses. Lens brand had a measurable
      effect on acuity for toric contact lenses. Further investigation of aberrations
      induced by contact lens design is warranted to explain the observed differences
      in visual performance.

PMID- 18049363
TI  - The development of validated bulbar redness grading scales.
AB  - PURPOSE: To develop a perceptually and physically based bulbar redness grading
      scale. METHODS: Digital conjunctival hyperemia photographs were taken using a
      photo-slit lamp at controlled exposures. Nine participants arranged 25 images on
      a tabletop over a range of 1.5 m, using separation to represent changes in
      redness. The position of each image was recorded and normalized for a 0 to 100
      scale, and compared to chromaticity of each image obtained using a
      spectrophotometer. The performance of two versions of the scale (5 and 10 images)
      and a continuous grading scale was evaluated based on repeatability data
      collected from nineteen observers who used each scale twice to grade 30 randomly
      presented images of bulbar redness. RESULTS: Psychophysical scaling was highly
      correlated between single observers (Pearson's r >or= 0.92, p < 0.05). The
      averaged subjective grades significantly correlated with chromaticity (r = 0.95
      and r = 0.99, p < 0.001 for CIE u* and log u*, respectively). Across all
      observers, test and retest ratings were highly correlated with either scale (r
      >or= 0.98), and showed high levels of repeatability expressed by intraclass
      correlation coefficients (ICC >or= 0.98), correlation coefficients of concordance
      (CCC >or= 0.96), and coefficients of repeatability (COR <or= 5.64). Despite
      single unit increment options, the majority of grade values assigned using the
      discrete scales were distributed in multiples of 5. CONCLUSIONS: Combining
      psychophysical and physical attributes is a promising method for the development
      of novel anterior segment scales; the newly developed scales performed well in a
      clinical setting.

PMID- 18049364
TI  - On the longitudinal chromatic aberration of the intraocular lenses.
AB  - PURPOSE: Primary properties of the optical materials used for intraocular lenses
      (IOLs) are biocompatibility and stability over time after implantation.
      Additionally, modern IOLs need to be flexible to be implanted through a small
      incision. Several compounds are usually added to existing materials (such as
      acrylic) to enhance the above-mentioned properties. Moreover, UV-absorbing
      substances are added in the IOL materials to mimic the spectral transmittance of
      the natural lens. Although manufacturers usually provide information for the
      geometry of IOLs, chromatic dispersion data are usually not available. The
      purpose of this study was to estimate the dispersion properties of a few
      materials used for IOLs. METHODS: We measured the chromatic focal shift of two
      common types of IOLs using a simple, optical method. From the chromatic focal
      shift, we calculated the dispersion properties of the materials
      (polymethylmethacrylate and acrylic) used for the IOLs under investigation.
      RESULTS: The results deviate from the existing data in the literature for the
      corresponding pure materials. CONCLUSIONS: The presence of the UV absorber in the
      optical material significantly affects its dispersive properties. Longitudinal
      chromatic aberration (LCA) of the IOLs is approximately three times higher than
      LCA of the natural crystalline lens. It is expected that eyes implanted with IOLs
      suffer from increased LCA in comparison with intact eyes. It remains to be
      investigated if this increase in LCA has a significant impact on visual function.

PMID- 18049365
TI  - Changes in lens dimensions and refractive index with age and accommodation.
AB  - PURPOSE: To measure changes in human eye lens dimensions and refractive index
      with age and state of accommodation. METHODS: MRI methods were used to measure
      refractive index maps and lens geometry (diameter and thickness) of an axial
      slice through the lens in 44 volunteers aged 18 to 59 years, with an
      accommodation stimulus of 0.17 D (unaccommodated state). In a subpopulation of 26
      young volunteers aged 18 to 33 years, lens dimensions were also measured in an
      accommodated (6.67 D stimulus) state. For a subpopulation of six of the young
      volunteers (22 to 33 years), refractive index maps were also acquired with an
      accommodation stimulus of 6.67 D. RESULTS: Unaccommodated lens thickness
      increased significantly with age (T = 3.31 +/- 0.10 mm + 0.0180 +/- 0.0036 mm x
      Age; p < 0.0001). Lens diameter (D = 9.33 +/- 0.0033 mm) and central refractive
      index (nc = 1.4198 +/- 0.0067) showed no significant age dependence. Lens
      thickness increased (DeltaT = 0.050 +/- 0.024 mm/D) and diameter decreased
      (DeltaD = -0.067 +/- 0.030 mm/D) on accommodation. A slight decrease in central
      refractive index with accommodation was not statistically significant.
      CONCLUSIONS: The results are consistent with the Helmholtz theory of
      accommodation.

PMID- 18049367
TI  - Acanthamoeba keratitis.

PMID- 18049369
TI  - Quadrivalent human vaccine - a call to action and for additional research.

PMID- 18049370
TI  - Retinoic acid fails to reverse oligohydramnios-induced pulmonary hypoplasia in
      fetal rats.
AB  - All-trans retinoic acid (ATRA) stimulates platelet-derived growth factor (PDGF)-A
      expression and enhances alveolarization in rat lungs. On d 16 of gestation,
      pregnant Sprague-Dawley rats were randomly assigned to either a retinoic acid
      group (intragastric ATRA at 10 mg/kg body weight) or a vehicle group. We
      punctured each amniotic sac, and fetuses in the opposite uterine horn served as
      controls. On d 21 of gestation, the fetuses were delivered by cesarean section.
      Rats subjected to oligohydramnios exhibited significantly lower lung weights and
      lung/body weight ratios, and ATRA had no effects on the body or lung weights of
      oligohydramnios-exposed rats. Lung PDGF-A and -B mRNA expression was
      significantly lower in oligohydramnios-exposed rats compared with control
      littermates of maternal vehicle-treated dams. Maternal retinoic acid treatment
      significantly increased PDGF-A and -B mRNA expression in control and
      oligohydramnios-exposed rats compared with all rats and oligohydramnios-exposed
      rats of maternal vehicle-treated dams, respectively. Rats exposed to
      oligohydramnios exhibited a significantly lower generation of alveolar saccules
      than did control rats in the maternal retinoic acid- and vehicle-treated groups.
      In this model, maternal retinoic acid treatment showed no positive effects on
      oligohydramnios-induced pulmonary hypoplasia in the pseudoglandular stage.

PMID- 18049371
TI  - Resuscitation of hypoxic newborn piglets with oxygen induces a dose-dependent
      increase in markers of oxidation.
AB  - Newborn resuscitation with pure oxygen may be associated with long-term
      detrimental effects. Due to the change in attitude toward use of less oxygen upon
      resuscitation, there is a need to study effects of intermediate hyperoxia. The
      aim was to study dose-response correlation between inspiratory fraction of oxygen
      used for resuscitation and urinary markers of oxidative damage to DNA and amino
      acids. Hypoxemia was induced in newborn piglets following a standardized model;
      they were resuscitated for 15 min with either 21%, 40%, 60% or 100% oxygen and
      observed for 1 h. Urine samples were collected. Urinary elimination of 8-hydroxy
      2'-deoxyguanosine (8-oxo-dG), 2'deoxyguanosine (2dG), ortho-tyrosine (o-Tyr) and
      phenylalanine (Phe) were determined by HPLC and tandem mass spectrometry (HPLC
      MS/MS). Quotient of 8-oxo-dG/2dG and o-Tyr/Phe ratios were significantly and dose
      dependant higher in piglets resuscitated with supplementary oxygen. 8-oxodG/dG:
      Mean (SD) 5.76 (1.81) versus 22.44 (12.55) p < 0.01 and o-Tyr/Phe: 19.07 (10.7)
      versus 148.7 (59.8)for 21% versus 100%, p < 0.001. Hypoxia and subsequent
      resuscitation for 15 min with graded inspiratory fraction of oxygen causes
      increased oxidative stress and a dose-dependant oxidation of DNA and
      Phenylalanine. The increase in the hydroxyl attack may lead to a pro-oxidative
      status and risk for genetic instability.

PMID- 18049372
TI  - Cytotoxicity is predicted by unbound and not total bilirubin concentration.
AB  - Although it has been suggested that the unbound, free, (B(f)) rather than total
      (B(T)) bilirubin level correlates with cell toxicity, direct experimental
      evidence supporting this conclusion is limited. In addition, previous studies
      never included a direct measurement of B(f), using newer, accurate methods. To
      test "the free bilirubin hypothesis", in vitro cytotoxicity was assessed in four
      cell lines exposed to different B(f) concentrations obtained by varying
      B(T)/Albumin ratio, using serum albumins with different binding affinities,
      and/or displacing unconjugated bilirubin (UCB) from albumin with a sulphonamide.
      B(f) was assessed by the modified, minimally diluted peroxidase method.
      Cytotoxicity varied among cell lines but was invariably related to B(f) and not
      B(T). Light exposure decreased toxicity parallel to a decrease in B(f). In the
      absence of albumin, no cytotoxicity was found at a B(f) of 150 nM whereas in the
      presence of albumin a similar B(f) resulted in a 40% reduction of viability
      indicating the importance of total cellular uptake of UCB in eliciting toxic
      effect. In the presence of albumin-bound UCB, bilirubin-induced cytotoxicity in a
      given cell line is accurately predicted by B(f) irrespective of the source and
      concentration of albumin, or total bilirubin level.

PMID- 18049373
TI  - Transient inhibition of astrocytogenesis in developing mouse brain following
      postnatal caffeine exposure.
AB  - Caffeine is frequently administered in human preterm newborns. Although some data
      suggest a potential risk for the developing brain, its impact has not been fully
      evaluated. We used a murine model of postnatal caffeine treatment in which mouse
      pups received intraperitoneal injections of caffeine from postnatal days 3 to 10.
      Caffeine exposure resulted in a transient reduction of glial fibrillary acidic
      protein and S100beta protein expression in various brain areas during the first 2
      postnatal weeks (19.8% and 23.2% reduction in the hippocampus at P15,
      respectively). This effect was dose-dependent and at least partly involved a
      reduction of glial proliferation, as a caffeine-induced decrease of 5
      bromodeoxyuridine incorporation was observed in the dentate gyrus and
      subventricular zone (25.8% and 26.6%, respectively) and no increase of programmed
      cell death (cleaved caspase-3 immunostaining) was observed at postnatal day 7.
      This effect could be reproduced with an antagonist of A(2a) adenosine receptor
      (A(2a)R) and was blocked by co-injection of an agonist. These results suggest
      that postnatal caffeine treatment might induce an alteration of astrocytogenesis
      via A(2a)R blockade during brain development. Although no obvious neuritic
      abnormalities (microtubule-associated protein 2 and synaptophysin immunostaining)
      were observed, postnatal caffeine treatment could have long-term consequences on
      brain function.

PMID- 18049375
TI  - Evolving microbiology and molecular epidemiology of acute otitis media in the
      pneumococcal conjugate vaccine era.
AB  - The addition of the 7-valent pneumococcal conjugate vaccine (PCV7) to the routine
      immunization schedule in the United States for infants has produced a much more
      favorable impact on the incidence of acute otitis media (AOM) than anticipated.
      Because the serotypes included in PCV7 were those most frequently expressing
      antibiotic resistance in 2001, predictions were made that up to 98% of
      pneumococcal AOM episodes would be caused by penicillin susceptible strains.
      However, recent studies have shown that the benefits of PCV7 are becoming eroded.
      Replacement serotypes of pneumococci have emerged, expressing polysaccharide
      capsules different from those included in PCV7, with increasing frequency. These
      replacement strains are coming to dominate in the nasopharynx and in AOM isolates
      (and in invasive disease). Expansion in the isolation of serotypes 3, 7F,
      15B/C/F, 19A, 22F, 33F, and 38 has been described in various surveillance
      systems. Pneumococcal strains expressing non-PCV7 capsular serotypes also appear
      to be rapidly acquiring resistance to penicillin and other antibiotics. Emergence
      of strains of pneumococci expressing non-PCV7 capsular serotypes is occurring by
      multiple mechanisms including capsular switching as suggested by molecular
      epidemiology studies. Expansion of the number of serotypes included in
      pneumococcal conjugate vaccines is needed to sustain a long-term benefit from
      immunization against these bacteria.

PMID- 18049376
TI  - Bacterial biofilms in otitis media: evidence and relevance.
AB  - A biofilm is a highly organized, multicellular network of bacteria encased in a
      matrix and found in close association with a surface. Substantial effort in
      understanding the biologic and biochemical nature of biofilms has resulted in
      evidence supporting their importance in otitis media (OM), both from the
      perspective how pathogens develop viable communities in the middle ear as well as
      how this structure impedes successful antibiotic therapy. This new understanding
      may explain the recurrent nature of OM, and the persistence of middle ear fluid
      after infection. This article looks closely at biofilms in OM and suggests that
      an improved understanding of the unique properties of bacteria resident within a
      biofilm and the proteins they express while part of this organized community has
      the potential to identify novel and perhaps biofilm-specific molecular targets
      for the design of vaccine candidates for the prevention of OM.

PMID- 18049377
TI  - Prospects for prevention of otitis media.
AB  - Understanding the pathogenesis of acute otitis media provides insight into
      strategies for immunoprophylaxis. This article evaluates the interactions between
      pathogen and host defense, and identifies potential bacterial and viral vaccine
      targets. Discussed in detail are the attributes for a candidate antigen necessary
      to achieve a greater reduction in the burden of middle ear disease. These
      include: (1) the need to target a broad spectrum of otopathogens; (2) antigens
      need to be shared across all (or most) isolates within a bacterial species; (3)
      antigens need to be surface exposed during middle ear infection; and (4)
      preferred antigens have an essential function such that nonexpressing bacterial
      mutants have reduced virulence. A vaccine candidate (Pnc-PD) that encompasses
      these "attributes" is discussed from the perspective of how it may provide
      additional protection from middle ear disease if further studies confirm initial
      data on efficacy.

PMID- 18049380
TI  - The burden and outcome of respiratory tract infection in Australian and
      aboriginal children.
AB  - The burden of otitis media in developing and disadvantaged populations is
      substantial. This article looks at that burden in developed affluent and
      indigenous populations (in Australia). A model is presented to explain the high
      prevalence of chronic suppurative otitis media in indigenous populations, and an
      assessment of efforts to improve these outcomes if not prevent these infections
      is provided. Lastly, various international guidelines for managing acute otitis
      media are compared.

PMID- 18049381
TI  - The challenge of recalcitrant acute otitis media: pathogens, resistance, and
      treatment strategy.
AB  - Recalcitrant acute otitis media (AOM), including 2 well-defined and sometimes
      related entities (persistent AOM and recurrent AOM), is a common pediatric
      problem. Episodes of AOM in children with either persistent or recurrent AOM were
      shown to be associated with recovery of middle ear fluid bacterial pathogens
      (particularly Streptococcus pneumoniae) with higher resistance to antibiotics
      compared with children with AOM not recently treated with antibiotics. The
      relationships between nasopharyngeal carriage of Streptococcus pneumoniae and
      persistence of middle ear fluid pathogens despite clinical improvement or cure
      and subsequent recurrence are discussed in depth. The findings emphasize the
      importance of bacteriologic eradication in the prevention of recurrent AOM
      episodes.

PMID- 18049383
TI  - Probabilistic risk analysis is practical.
AB  - This article shows how health care organizations can analyze their reported near
      miss and sentinel events using probabilistic risk analysis (PRA). The specific
      aims are to model risks and identify known hazards that threaten patient safety.
      This article provides an introduction to PRA. To demonstrate how the approach
      could work with small data sets, we provide a tutorial for analysis of 10
      incidences of medication errors. We show that time to errors can be used to
      measure progress in reducing medication errors. We show that the influence of
      various causes of errors can be quantified on the basis of the prevalence of the
      cause among a handful of incidences and among the error-free cases. PRA enables
      health care organizations to (1) incorporate objective data into the
      deliberations of the safety teams, (2) gauge even small progress in incidences of
      sentinel events, and (3) set objective priorities for risk-reduction strategies.
      Critics may argue that PRA is too complicated to learn and has onerous data
      requirements. This is not true. We report on training of health care analysts who
      successfully analyzed risks within health care organization within 2 months time
      using the PRA. The training of these analysts and their success in applying their
      new learned skills show that the approach is practical.

PMID- 18049384
TI  - Tutorial on discrete hazard functions.
AB  - Risk analysis requires estimation of hazard functions. A hazard rate is the
      conditional probability of adverse sentinel event occurring in the next time
      period, given that it has not yet occurred. This tutorial shows how hazard
      functions are estimated from survival functions, the probability of going through
      a time period without the sentinel event. Survival functions are built on
      cumulative distribution functions, which measure the probability of occurrence of
      sentinel event in current and prior time periods. Cumulative distribution
      functions are calculated from probability density functions, which give the
      probability of an event occurring at a particular time period. Probability
      density functions are typically estimated from incidence reports, which are
      readily available to safety officers. Sometimes, these functions are estimated by
      making assumptions about the shape of the distribution function. For discrete
      data, the typical probability density functions are Bernoulli, Binominal,
      Geometric, and Poisson distributions. This tutorial starts with estimating a
      probability distribution and then proceeds to calculation of hazard and relative
      risk rates.

PMID- 18049385
TI  - Tutorial on monitoring time to next medication error.
AB  - Alemi and colleagues in this issue of the journal have proposed that rare events
      can be monitored by shifting from frequency of the event to the examination of
      the time to the event. This article examines their claim with data obtained from
      an acute care hospital in the United States. We examined the data on medication
      omissions to see whether changes in underlying process can be detected through
      control charts. Medication errors are rare; the article examines medication
      errors due to omission, which makes the phenomena rarer. The empirical question
      was whether changes in process of care could be detected using control charts
      from data on medication omissions. Two different types of control chart, the XmR
      and Tukey charts, were used to analyze the data. The control chart with the
      tightest control limits was chosen for further interpretation. The XmR chart
      showed that there was sufficient power to detect unusual days in which the time
      to omission error was higher than historical norm. This article suggests that
      even rare events can be monitored through judicious use of time to the event. It
      shows the viability of safety teams using time to sentinel events to monitor
      progress in reducing frequency of sentinel events.

PMID- 18049386
TI  - Root cause analysis and Bayesian networks of Down syndrome and necrotizing
      enterocolitis.
AB  - OBSERVATION: This study demonstrates the use of root cause analysis and Bayesian
      networks in assessing risk of Down syndrome and infant mortality due to
      necrotizing enterocolitis (NEC). SUBJECTS AND METHODS: The contribution of
      maternal age, ethnicity, smoking, and infant's comorbidities on mortality
      associated with NEC (83 cases) was investigated using data obtained from the
      North Carolina linked birth/infant death files from 1999 to 2003. The data
      related to Down syndrome, which included 747 infants born with Down syndrome
      between the years of 1999 and 2003, were provided by the North Carolina Birth
      defects Monitoring Program. Flowcharts were built to identify potential risk
      factors and their associations, while the Bayesian network methodology was
      utilized to encode probabilistic relationships among these variables. RESULTS AND
      CONCLUSIONS: On the basis of the NEC model, the 3 most common causes of NEC
      infant mortality were respiratory tract conditions, cardiac, and infection
      related problems. For the second application, prior live births (at least 1 prior
      birth) and infant's gender (male) were found to be the most prevalent causes of
      Down syndrome. Bayesian belief networks constitute an excellent tool for
      explorative and causal data analysis, and can assist health care providers in
      gaining insight into a complex problem.

PMID- 18049387
TI  - Risk analysis of falls in an assisted living community.
AB  - PURPOSE: A tutorial in the utilization of probabilistic risk analysis to analyze
      the causes of falls in the ambulatory population of an assisted living community.
      METHODS: Review of 9 documented incidents of resident falls and interviews with
      staff regarding the probability of fall causes. A literature review was also
      conducted. RESULTS: Age-related physiological changes in conjunction with
      medical/diseases demonstrate a higher risk of falls than age-related
      physiological changes alone. CONCLUSIONS: The utilization of the fall risk model
      can aid in identifying the risk factors and the probability of the causes
      associated with documented falls to identify residents with the propensity to
      have a fall-related injury given a small set of data. Additional research will
      enhance the findings of additional fall-related causes.

PMID- 18049389
TI  - Probabilistic risk analysis of medication error.
AB  - Over the years, the United States has spent billions of dollars in its quest to
      improve the quality and safety of health care through the development of new
      drugs and technologies. Using the probabilistic risk analysis of medication error
      process, we demonstrate the application of Bayesian Causal Network Model to
      assess the probabilities of occurrence of rare events related to medication
      errors. This article summarizes the methodology involved in the process. METHODS:
      A convenience sample of annual incident reports from a Northeast acute care
      community hospital was used for the study. Importance sampling was used to
      improve the accuracy of estimates of the rare events so that we can better
      understand the relationship of causes within the reported events. DISCUSSION: The
      Bayesian Causal Network Model provided contextual maps of the behaviors and
      errors that lead to medication delivery process failures, including unanticipated
      risks associated with actual errors as well as near misses and common deviations
      from standard procedures and policies. Health care administrators, clinicians,
      regulators, and educators can prospectively identify and prioritize risk
      reduction interventions using the Bayesian Causal Network Model. CONCLUSIONS: The
      Bayesian Causal Network Model can identify behavioral and systemic factors that
      can enhance or reduce the risk of wrong drug, wrong frequency, wrong dose,
      omitted dose, drug interactions, and wrong patient medication errors in
      hospitals.

PMID- 18049388
TI  - Utilization of failure mode effects analysis in trauma patient registration.
AB  - AIM: Our goal was to identify strategies that would reduce risks and improve
      patient safety during registration of trauma patients and subsequent electronic
      data linkage. Recently, the health care industry and the Joint Commission on
      Accreditation of Healthcare Organizations have supported failure mode effects
      analysis (FMEA) as a tool for proactively reducing risk to patients. METHODS: We
      utilized FEMA for a comprehensive evaluation of our trauma patient registration
      process for system weaknesses. RESULTS: We found several areas of our processes
      that placed patients at risk. On the basis of our findings, we implemented
      changes that included education of staff, role clarification, task reallocation,
      and established a list of personnel authorized to request the electronic data
      linkage process. Further recommendations were made for information system
      changes, which are under review. CONCLUSIONS: FMEA helped us to systematically
      identify and prioritize risks to patient safety. Our findings directed changes,
      which, in turn, reduced potential errors. We recommend this method of evaluation
      to other health care personnel interested in improving patient safety.

PMID- 18049392
TI  - Laparoscopic highly selective vagotomy with nissen fundoplication: is there any
      role?
AB  - INTRODUCTION: Nissen fundoplication (NF) has not been a uniformly successful
      treatment for gastroesophageal reflux disease (GERD). Acid lowering procedures
      such as highly selective vagotomy (HSV) have not yet been fully evaluated as an
      adjunctive treatment. NFHSV was evaluated in GERD. MATERIALS AND METHODS: Between
      June 2003 and June 2005, 8 women with a history of 6 months of GERD unrelieved by
      medication, preprandial pain, peptic ulcer disease, or severe gastritis underwent
      laparoscopic NFHSV. They have been followed for a mean 12 months. Preoperative
      and postoperative Heartburn Severity scores (HSS) were obtained. RESULTS: Mean
      operative time was 110 minutes. There were no complications. One patient needed
      postoperative proton pump inhibitor, which was discontinued after smoking
      cessation 5 months after NFHSV. All 8 patients showed marked improvement in
      symptoms and HSS. CONCLUSIONS: This series lends credence to the notion that
      NFHSV was effective. Several studies need to be performed to demonstrate the full
      efficacy and safety of this approach.

PMID- 18049393
TI  - Use of surgisis mesh in laparoscopic repair of hiatal hernias.
AB  - BACKGROUND: Breakdown of the crural closure is a frequent reason for failure of
      antireflux surgical procedures. This retrospective study aimed to determine the
      effectiveness of using absorbable mesh in preventing recurrence of hiatal hernia
      after posterior cruroplasty. DESIGN: Comparative retrospective analysis. METHOD:
      The charts of 220 adults who underwent antireflux surgery with posterior
      cruroplasty between 1997 and 2005 were retrospectively reviewed. Patients were
      divided into 2 groups: posterior cruroplasty+absorbable mesh reinforcement
      (n=127) and posterior cruroplasty alone (n=93). Symptomatic outcome was assessed
      by telephone interview in 92 patients (72%) in the mesh group at a median of 3.2
      years postoperatively and 59 patients (63%) in the no mesh group of men studied
      at a median of 3.8 years postoperatively. MAIN OUTCOME MEASURES: Incidence of
      recurrence and persistent symptoms. RESULTS: In the mesh group, 74/92 (80%)
      patients remained asymptomatic at a median of 3.2 years postoperatively. Of these
      patients, 31 underwent either an upper endoscopy or an upper gastrointestinal
      (UGI) series; none had recurrence of hiatal hernia. Of the 18 symptomatic
      patients, 13 underwent an upper endoscopy or an UGI series to determine the
      etiology of symptoms; 3 recurrences were confirmed for a 3.3% overall proven
      recurrence rate. In the no mesh group, 26/59 (44%) patients were symptomatic. Of
      these, 18 underwent either an upper endoscopy or an UGI series. Recurrence of
      hernia was confirmed in 12 patients for a 20% overall proven recurrence rate.
      There were no instances of mesh infection or erosion. CONCLUSIONS: Symptomatic
      recurrence rates of hiatal hernia after antireflux surgery vary. Recurrence of a
      hiatal hernia may or may not lead to symptoms. This retrospective analysis
      demonstrates that absorbable mesh is safe and may lead to a significant reduction
      in the incidence of symptomatic recurrent hiatal hernia.

PMID- 18049394
TI  - Laparoscopic anterior cardiomyotomy plus anterior Dor fundoplication without
      division of lateral and posterior periesophageal anatomic structures for
      treatment of achalasia of the esophagus.
AB  - Laparoscopic cardiomyotomy is the treatment of choice for patients with achalasia
      of the esophagus. Several different techniques and modifications have been
      reported concerning the approach (thoracoscopic or laparoscopic), type and length
      of the myotomy, with or without fundoplication, type of fundoplication, etc. In
      this prospective study, we report our simplified technique for anterior
      cardiomyotomy with Dor fundoplication and the results obtained using this
      procedure. Only the anterior wall of the esophagus was exposed without dissection
      of the lateral or posterior periesophageal anatomic structures for the technique.
      Twenty-five patients were operated by a single surgeon. The diagnosis was based
      on the clinical, radiologic, endoscopic, and functional esophageal tests.
      Achalasia was classified into 3 types: achalasia type I was diagnosed in 5
      patients, type II in 6 patients, and type III in 14 patients. Manometry
      demonstrated a mean resting pressure of 33.5 mm Hg (range, 18 to 55), associated
      with incomplete relaxation. The hospital stay was 3 days; the median operative
      time was 115 minutes (range, 90 to 150), 2 small mucosal perforations occurred
      which were immediately sutured during surgery without conversion into open
      technique and no postoperative complications occurred. After operation, lower
      esophageal sphincter pressure returned to normal values and complete relaxation
      in all patients. In type II and III achalasia, the esophageal body diameter
      decreased more than 50% (P=0.001) compared with the preoperative diameter, and
      the internal diameter of the esophagogastric junction increased significantly
      (P=0.001). Only 2 patients presented occasional heartburn and 2 patients received
      1 session of hydrostatic dilatation due to mild residual dysphagia. No late
      recurrence of dysphagia has been observed to the present time (1 to 5 y of follow
      up). In conclusion, the goals of the surgery for achalasia are obtained with this
      simplified technique.

PMID- 18049395
TI  - Needlescopic Cholecystectomy Versus Needlescope-assisted Laparoscopic
      Cholecystectomy.
AB  - This clinical study was performed to compare the feasibility, safety, and best
      use of the needlescope and needlescopic instruments. Needlescopic cholecystectomy
      (NC) or needlescope-assisted cholecystectomy (NAC) was performed in 40 cases of
      gallbladder (GB) stone or polyp. There were 12 men and 28 women, with a mean age
      of 51.8 years (range, 27 to 79 y). The port sites consisted of three 2-mm ports
      at the right upper quadrant and one 12-mm port at the umbilicus. To evaluate the
      feasibility and safety of the needlescope, the time taken to perform each
      operative step was compared for NC and NAC. Operation time was divided into: (1)
      skin incision to insertion of the 4 ports; (2) insertion of the 4 ports to
      cannulation into the cystic duct; (3) time of intraoperative cholangiography
      (IOC); (4) skin incision to cutting of the cystic duct without IOC; (5) cutting
      the cystic duct to dissection of the GB; (6) dissection of the GB to removal of
      the GB; (7) removal of the GB to skin closure; and (8) total operation time. IOC
      was performed successfully in 10 cases of NC and 10 cases of NAC. Respective mean
      times of the 8 steps were 5.4 versus 5.3 minutes, 34.2 versus 32.2 minutes, 20.1
      versus 18.4 minutes, 33.9 versus 31.3 minutes, 19.6 versus 18.9 minutes, 3.1
      versus 2.9 minutes, 10.0 versus 10.2 minutes and 82.5 versus 77.8 minutes for NC
      versus NAC, respectively. There were no significant differences in any of the
      factors related to surgical procedures between the 2 groups, and there were no
      perioperative complications. The use of a needlescope and needlescopic
      instruments was feasible and safe for laparoscopic cholecystectomy in both
      surgical laparoscopic procedures for highly selected patients.

PMID- 18049396
TI  - Laparoscopic cholecystectomy: complications and conversions with the 3-trocar
      technique: a 10-year review.
AB  - BACKGROUND: Traditional laparoscopic cholecystectomy (LC) includes the use of 4
      trocars. The aim of this study is to show that LC can be performed safely with
      the 3-trocar technique, thus simplifying a very well-known technique. METHODS: We
      performed a retrospective analysis of 1878 patients (male-to-female ratio was
      1:3; median age of 44 y) that underwent 3-trocar LC between May 1994 and December
      2004. RESULTS: Three-trocar LC was successful in 1774 patients (94%) with a
      postoperative morbidity of 1.5% (0.5% of major complications), which includes 2
      minor common bile duct lesions (type D according to Strasberg classification) and
      1 right common iliac artery laceration. Mortality was nil. Among 249 cases of
      acute cholecystitis, the 3-trocar LC was successful in 172 patients (70%). The
      adoption of a fourth trocar was necessary in only 82 patients (4.3%). Conversion
      to laparotomy occurred in a total of 67 patient (3.5%), 22 of which directly from
      the 3-trocar technique. The median operating time of the 3-trocar LC was 40
      minutes (range, 16 to 130) for chronic cholecystitis, and 80 minutes (range, 30
      to 145) for acute cholecystitis. The difference in duration of the surgical
      procedure between the 2 groups was significant (P<0.05). Severe adhesions were
      more commonly the reason for conversion (P<0.05). CONCLUSIONS: The study achieves
      to conclude that the 3-trocar technique can be safely performed, is not
      technically demanding, and yields in experienced hands a complication rate
      comparable with the conventional LC. Furthermore, it is less expensive and has a
      better cosmetic result.

PMID- 18049398
TI  - Laparoscopic proctocolectomy with ileal pouch-anal anastomosis.
AB  - In recent years laparoscopic proctocolectomy with ileal pouch-anal anastomosis
      has been used as an alternative to conventional open techniques. However, many
      published series on proctectomy and ileal pouch-anal anastomosis are based on
      open experience. This paper presents our experience of laparoscopic
      proctocolectomy with ileal pouch-anal anastomosis to 23 patients with ulcerative
      colitis and familial adenomatous polyposis. In operations only sample
      exteriorization and pouch formation were performed using a small left flank
      incision of about 4 cm, all other steps were performed entirely laparoscopically.
      None of the laparoscopic procedures required conversion to an open operation, and
      there were no intraoperative complications. The median operative time was 315
      minutes (240 to 460 min), the average blood loss was 130 mL (70 to 270 mL).
      Postoperative pain was minimal and no patients required analgesic drugs. Bowel
      function returned in a median of 2 days (1 to 3 d). Postoperative complications
      were encountered in 5 patients 22%). No patient required surgical reintervention.
      The median hospital stay was 9 days (7 to 16 d). In conclusion, laparoscopic
      proctocolectomy with ileal pouch-anal anastomosis is technically feasible and
      safe. The technique described in this study provides some potential advantages
      such as improved cosmetic result and less blood loss. It can be used in patients
      with familial adenomatous polyposis and ulcerative colitis.

PMID- 18049397
TI  - Comparison of iatrogenic splenectomy during open and laparoscopic colon
      resection.
AB  - Iatrogenic splenic injury requiring splenectomy is a well-recognized and
      potentially serious complication of colon resection. Iatrogenic splenectomy is
      associated with significant morbidity and mortality, including bleeding and the
      postsplenectomy sepsis syndrome. Our study aims to compare the incidence of
      iatrogenic splenectomy in laparoscopic colon resection with that of open colon
      resection over an 11-year-period at Mount Sinai. A retrospective chart review of
      all patients undergoing colon resection at Mount Sinai Medical Center during the
      last 11 years was performed to identify patient demographics, procedure,
      indication, and outcome. There was a significant difference (P=0.03) in the
      incidence of iatrogenic splenectomy during open colectomy (13/5477, 0.24%) versus
      laparoscopic colectomy (0/1911, 0%). All cases complicated by iatrogenic
      splenectomy involved splenic flexure mobilization. Laparoscopy has many
      recognized advantages over open procedures, including shorter recovery and length
      of stay. This retrospective review of our experience at Mount Sinai presents
      another potential benefit of the laparoscopic approach to colon resection.

PMID- 18049399
TI  - Laparoscopic adrenalectomy (LA): keys to success: correct surgical indications,
      adequate preoperative preparation, surgical team experience.
AB  - BACKGROUND: Laparoscopic adrenalectomy (LA) has become the surgical procedure of
      choice for the treatment of most adrenal lesions. Controversy still remains about
      the treatment for primary and secondary malignant lesions and for
      pheochromocytoma. MATERIALS AND METHODS: From September 1997 to December 2005, 77
      patients were operated on for adrenal tumors in a single center. Three patients
      had bilateral lesion for a total of 80 adrenalectomies. Selection criteria for
      laparoscopic treatment included benign characteristics of the lesions regardless
      of size and absence of virilization syndrome. A multidisciplinary approach was
      used for adequate preparation of patients with functional lesions. Fifty-five
      patients were eligible for LA and 22 for open surgery. RESULTS: Mean operative
      time was 142 minutes (range 45 to 240) in the laparoscopic group (53 patients)
      and 161 minutes (range 90 to 300) for the open group (24 patients). In 2 patients
      (4%) conversion to open procedure was necessary for intraoperative bleeding.
      Laparoscopic surgery in patients with pheochromocytoma was associated with a
      better intraoperative hemodynamic stability. CONCLUSIONS: LA is the treatment of
      choice for benign adrenal tumors regardless of size. Appropriate selection of
      patients, adequate preoperative preparation of patients with functional lesions
      and expertise in adrenal surgery and advanced laparoscopic skills are necessary
      to allow reduction of perioperative morbidity and early recovery.

PMID- 18049400
TI  - Laparoscopy offers diagnosis and treatment in abdominal stab injuries.
AB  - PURPOSE: To assess the role of laparoscopy in the diagnosis and treatment of
      abdominal stab injuries (ASI). METHODS: Patients who underwent laparoscopic
      procedures due to ASI were included in the study. Hemodynamic instability,
      injuries to the posterior trunk, concomitant severe cranial injuries, and prior
      abdominal operations were considered as contraindication for laparoscopy.
      RESULTS: From January 1997 to March 2006, 88 patients underwent laparoscopic
      management of ASI. In 45 patients (51.1%), there was no intra-abdominal pathology
      requiring surgical intervention (nontherapeutic laparoscopy) and 5 patients in
      this group had no peritoneal penetration (negative laparoscopy). In another 25
      patients (28.4%), laparoscopic treatment was performed (therapeutic laparoscopy),
      including bleeding control in liver, colonic, gastric, and diaphragmatic repairs
      and intra-abdominal bleeding control. Laparotomy was avoided in a total of 70
      (79.5%) patients. In 18 patients (20.5%), laparoscopy was converted to
      laparotomy. There was no mortality, and except one missed small bowel injury nor
      perioperative morbidity in patients undergoing laparoscopy. In the laparotomy
      group, major complications were seen in 7 patients. CONCLUSIONS: Laparoscopy is
      safe and efficient in the management of ASI and should be more frequently
      considered as a therapeutic tool.

PMID- 18049401
TI  - The impact of haptic learning in telemanipulator-assisted surgery.
AB  - BACKGROUND: The use of a telemanipulator requires special training and surgical
      performance is associated with a learning curve. The aim of this study was to
      demonstrate the potential value of Haptic-Visual over Visual-Only passive
      Training in telemanipulator-assisted surgery. METHODS: Two telemanipulator
      consoles (da Vinci, Intuitive Surgical) were linked through an Application
      Programer's Interface allowing the applicant at the training console to register
      the position and passively follow the motions of the instructor's master
      telemanipulators (MTMs) at the master console (Haptic-Visual Learning group,
      HVL). The applicant could not actively interfere with the MTM movements. Both the
      trainee and the instructor shared the same 3-dimensional vision. Alternatively,
      subjects received only standard visual training without touching the MTMs (Visual
      Only Learning group, VL). A standardized demonstration of tasks and the system
      was given for both groups. Participants (n=20) without previous experience with
      telemanipulation performed a set of various tasks in a randomized order. Study
      end points were time and accuracy required to perform the different task.
      RESULTS: The first task, with moving items to appropriate locations, showed
      differences in time to perform the task [mean: 4:06 min (HVL) vs. 5:16 min (VL)
      (P=0.2)] and accuracy differed among groups [mean number of errors 1.7 (VL) vs.
      1.3 (HVL) P=0.38]. With more challenging tasks [cut out round figures (cut) and
      performing double dot suture lines (sti)] the number of errors was less in the
      HVL group [mean: 1.1 errors (cut) (P=0.05) and 1.8 errors (sti) (P=0.26)]
      compared with the VL group [mean: 1.8 errors (cut) and 2.3 errors (sti)]. In
      addition, the time to perform the tasks decreased in the HVL group with mean:
      5.42 minutes (cut) (P=0.26) and 9.41 minutes (sti) (P=0.36) compared with the VL
      group with mean: 7.09 minutes (cut) and 11.43 minutes (sti). CONCLUSIONS: This
      study demonstrated the impact of haptic-visual passive learning in
      telemanipulator-assisted surgery which may alter the training for telemanipulator
      assisted endoscopic procedures.

PMID- 18049402
TI  - Endogastric surgery for gastric diseases--simplifying technical aspects.
AB  - Minimally invasive surgery has become the preferred treatment strategy for most
      gastrointestinal diseases. Owing to specific anatomical reasons and in highly
      selected patients, gastric diseases offer the opportunity for an endogastric
      approach. In this setting, 2 different strategies may be used: (1) endogastric
      mucosectomy for superficial lesions such as highly selected early gastric cancer
      and (2) stapled wedge resection for intramural lesions such as gastric stromal
      tumors. A detailed description of this simple and radical treatment option is
      performed which requires standard laparoscopic instrumentation and basic
      laparoscopic skills. With the widespread of this approach, endogastric surgery is
      expected to become the preferred initial step in the management of various
      gastric diseases.

PMID- 18049403
TI  - Virtually bloodless laparoscopic liver resection of recurrent hepatoma with a new
      laparoscopic sealer device: report of our initial laparoscopic experience.
AB  - Liver resections have always been challenging especially when dealing with
      hemostasis. This is even more true in the laparoscopic approach. Excessive
      intraoperative blood loss is known to increase morbidity and reduce survival of
      patients undergoing major cancer procedures. Multiple techniques and devices have
      been employed in the past to deal with this problem. Use of recent technologies
      such as radiofrequency energy for hemostasis in solid organs of both human and
      animals have been reported with promising results. The Habib Laparoscopic Sealer
      4XL device is a new instrument that functions using such energy sources. Since
      the first successful use of a similar device for removing a liver tumor was
      performed in September 2005, new hopes and horizons have been generated for the
      laparoscopic approach. We report our initial experience of using such a device
      for laparoscopic liver resections in our center.

PMID- 18049405
TI  - Completely minimally invasive approach to restorative total proctocolectomy with
      j-pouch construction in children.
AB  - Restorative total proctocolectomy with J-pouch is a procedure used for children
      with severe ulcerative colitis or premalignant conditions like familial
      polyposis. The classic approach requires a laparotomy incision. Most published
      minimally invasive techniques still require a somewhat smaller incision to
      complete the procedure. We present a completely minimally invasive approach to
      accomplish the same goal, using a combined laparoscopic and endorectal technique
      and present our current clinical results with this method.

PMID- 18049404
TI  - Vertical rotation and impaction to the choledochal duct of a migrated biliary
      self-expanding metal stent.
AB  - Self-expanding metal stent (SEMS) placement is a well accepted and highly
      effective method for both treating and palliating obstructive lesions of the
      biliary tree, still complications may occur including premature occlusion and
      stent migration. Migration can occur either proximally or distally, usually early
      after SEMS placement and almost exclusively in covered ones. Distal migration is
      the most common type and is reported in 5.8% to 6% of cases. In our case,
      proximal migration of the stent occurred and surprisingly it rotated and impacted
      to the common bile duct transversally. This precluded any attempt to reposition
      or remove the SEMS. We effectively treated this unusual complication by placing
      an additional plastic stent into the common bile duct that restored biliary
      drainage.

PMID- 18049406
TI  - Fisherman's technique, introducing a novel method for using the umbilical port
      for removal of appendix during laparoscopic appendectomy.
AB  - We describe a useful technique for removing the dissected appendix after
      laparoscopic appendectomy. This technique allows laparoscopic appendectomy to be
      completed with a single 10-mm and two 5-mm ports using only one 10-mm telescope.
      In this technique the dissected appendix is tied with an endoloop and then the
      end of this loop is railroaded through the umbilical port that will allow the
      appendix to be pulled (or fished) through the umbilical port. The advantage of
      this technique over older techniques is that it uses the full width of the 10 mm
      port, which makes it suitable for almost all cases with no chance of appendicular
      fragmentation during retrieval. The technique is safe, inexpensive, and does not
      need the use of retrieval bags.

PMID- 18049407
TI  - Application of laparoscopic techniques for resection of individual gastric
      submucosal tumors.
AB  - Large gastric submucosal tumors should be excised to prevent ischemic mucosal
      ulceration of the overlying surface and central necrosis of the neoplasm, which
      may in turn lead to massive hemorrhage. Large tumors near the esophagocardiac
      junction or on the posterior wall are usually resected by an open procedure. We
      describe 2 cases of upper gastrointestinal tract bleeding owing to huge
      submucosal tumors in the posterior gastric high body treated by laparoscopic
      resection of the gastric tumors. These 2 patients recovered smoothly without
      major or minor complications. We emphasize that design of specific strategies for
      individual tumors is essential for the successful laparoscopic resection of
      tumors adjacent to the esophagocardiac junction and large tumors on the posterior
      wall.

PMID- 18049408
TI  - Gastro-bronchial fistula after laparoscopic nissen fundoplication.
AB  - Gastro-bronchial fistula (GBF) is an unusual complication of Nissen
      fundoplication, particularly when performed via a transabdominal approach. The
      mechanism of such fistula is thought to be related to a previously untreated
      ulcer in the mucosa of the wall of the gastric wrap or to a subclinical injury to
      the gastric wall during the process of division of the short gastric vessels and
      gastric mobilization. This process is greatly aided by herniation of the wrap
      into the chest in the postoperative period, placing the stomach in intimate
      contact with the bronchial tree. The diagnosis of GBF is often difficult to
      establish and requires a high index of suspicion. Most investigative studies tend
      to be unrevealing. Historically, an upper gastrointestinal series was the
      recommended study of choice in the literature. Newer reports, however, highlight
      the value and importance of upper endoscopy as a diagnostic tool in this
      condition. The majority of GBF were reported in the era of transthoracic Nissen
      fundoplication. The incidence of this complication seems to have markedly
      decreased after the widespread adoption of the transabdominal approach to the
      treatment of GERD. We are reporting the second case in the literature of a GBF
      developing after a laparoscopic Nissen fundoplication in a 28-year-old male
      patient. This case report should serve to increase awareness of this uncommon
      complication that should be considered in the differential diagnosis of patients
      with recurrent pneumonia or refractory hemoptysis after major upper
      gastrointestinal surgical procedures.

PMID- 18049409
TI  - Ectopic papilla of vater in the stomach, blind antrum with aberrant pyloric
      opening, and congenital gastric diverticula: an unreported association.
AB  - We present an extremely rare combined congenital anomaly consisting of ectopic
      drainage of the common bile duct in the lesser curvature of the stomach,
      congenital gastric diverticula, blind antrum with aberrant pyloric opening, and
      redundant spleen. The diagnosis was made during routine endoscopy in a 35-year
      old woman, who presented complaining for regurgitation and retrosternal burning
      in the last 4 years. To our knowledge this is the first description of this rare
      combination of congenital anomalies. The possible embryogenetic backgrounds, and
      the possible clinical significance of this rare condition are discussed.

PMID- 18049410
TI  - Erosion of gastric electrical stimulator electrodes: evaluation, management, and
      laparoscopic techniques.
AB  - BACKGROUND AND OBJECTIVE: Gastric electrical stimulation is a promising
      technology for treatment of gastroparesis. Few studies address potential
      complications of the device. MATERIALS: We review the diagnosis and laparoscopic
      management of 2 cases of gastric stimulator (GS) electrode erosion through the
      gastric wall. RESULTS: Both patients presented with late (16 and 21 mo) device
      infection. Diagnosis of electrode erosion was verified by upper endoscopy. The
      electrodes were successfully removed laparoscopically. A new GS and electrodes
      were implanted laparoscopically in 1 patient 6 months later. CONCLUSIONS:
      Electrode erosion is an unusual complication. Surgeons must have a high index of
      suspicion for electrode erosion when patients present with late GS infections.
      Eroded electrodes can be removed and replaced laparoscopically.

PMID- 18049411
TI  - Laparoscopic-assisted colonoscopic polypectomy for juvenile polyp in children: a
      new minimal-invasive therapeutic approach.
AB  - An 8-year-old boy was hospitalized with fresh bloody stool passage for 1 week. He
      underwent colonoscopy that revealed 1 large polyp in the rectosigmoid junction.
      The polyp was too large to be encircled by the snare. Laparoscopic-assisted
      colonoscopic polypectomy was performed successfully to remove this large polyp
      without the need for segmental resections. This patient treated using this
      technique were discharged 2 days after the procedure and returned to full
      activity within 3 to 4 days. There were no complications.

PMID- 18049412
TI  - Laparoscopic resection for malignant lymphoma of the ileum causing ileocecal
      intussusception.
AB  - A 22-year-old man was admitted with right lower abdominal pain. Colonoscopy
      revealed a ball-like tumor at the ileum. Abdominal sonography and computed
      tomography showed ileocecal intussusception. Microscopic examination of the
      biopsy specimen showed malignant lymphoma. Laparoscopic ileocecal resection was
      performed. Histologic diagnosis of the resected tumor was diffuse large B cell
      type malignant lymphoma. Intussusception due to malignant lymphoma is relatively
      rare in adults. If contraindications of laparoscopy are not present, laparoscopic
      resection can be performed safely and should be considered for diagnosis and
      treatment for intussusception in ileocecal lesions in adults.

PMID- 18049413
TI  - Endoscopic closure of fecal colo-cutaneous fistula by using metal clips.
AB  - Fecal colo-cutaneous fistula often requires surgical intervention for successful
      closure increasing the morbidity and mortality associated with this condition.
      Endoscopic fistula closure can be a less invasive modality. We report successful
      closure of fecal colo-cutaneous fistula by endoscopic application of metal hemo
      clips after failure of prolonged treatment including diverting proximal ileostomy
      in 2 consecutive patients after emergency primary repair of cecal perforation
      caused by stab injury of abdomen and iatrogenic fecal fistula after left
      hemicolectomy and colo-colic anastomosis for adenocarcinoma of descending colon,
      respectively. The endoscopic closure of fecal colo-cutaneous fistula by using
      metal clips is an effective, safe, and less invasive treatment modality. It can
      add to therapeutic armamentarium of surgeons and may obviate the need for
      additional surgical intervention and associated morbidity in a proportion of such
      patients.

PMID- 18049414
TI  - Silent perforation: an iatrogenic complication of colonoscopy.
AB  - A 55-year-old woman presented with a complaint of 3 months of bloody diarrhea
      with an approximately 8 stools per day. She initially underwent a flexible
      sigmoidoscopy at an outside hospital with biopsies showing acute and chronic
      colitis. She was started on asacol 2 tablets 3 times per day. Her symptoms
      persisted and she was placed on prednisone with only transient improvement in her
      symptoms. She continued to have diarrhea and malaise with 30-lb weight loss over
      2 months. Outpatient colonoscopy was performed for evaluation of this change in
      bowel habit. Colonoscopy showed 2-cm terminal ileal polyp, focal ulcer of the
      cecum, and severe ulcerative colitis from mid-ascending colon to rectum, with
      touch friability, spontaneous bleeding, pseudopolyps, and ulceration. Multiple
      biopsies were taken of the friable and ulcerated regions. After colonoscopy, the
      patient remained stable with no complaints of pain. She was then taken for
      computed tomographic enterography showing severe colitis but also reflecting a
      large amount of air surrounding the right abdominal structures including the
      liver, gallbladder, right kidney, and right side of the colon. Air extended
      inferiorly into the right thigh and superiorly into the chest where it reached
      the mediastinum and pericardium. There was also a small amount of air in the
      peritoneal cavity under the diaphragm and adjacent to the liver. These findings
      were thought most likely secondary to asymptomatic colonic perforation secondary
      to colonoscopy. The patient remained stable, afebrile, and pain-free small bowel
      pathology from colonoscopy revealed carcinoid tumor of the terminal ileum. The
      patient remained stable despite intraperitoneal, retroperitoneal, and
      subcutaneous free air on follow-up x-ray. Patient underwent elective
      ileocecectomy 2 weeks later with postoperative films showing no evidence of free
      air. Iatrogenic perforation of the colon is a rare but feared complication of
      coloscopy with an incidence in some studies of 0.03% to 0.09%. This case
      demonstrates asymptomatic colonic perforation to a dramatic effect.

PMID- 18049415
TI  - Laparoscopic management of splenic cysts: marsupialization, cavity lining with
      surgicel and omentopexy to prevent recurrence.
AB  - INTRODUCTION: Open total splenectomy, once the treatment of choice for splenic
      cysts, has largely been replaced by laparoscopic, splenic preserving procedures.
      These techniques have resulted in reduced hospitalization times and rates of
      overwhelming postsplenectomy infection. We report 2 cases of laparoscopic
      management of large, symptomatic splenic cysts. METHODS: Two patients presented
      with symptomatic splenic cysts. The first was a simple cyst by history, the
      second a posttraumatic cyst. Both patients were treated by laparoscopic cyst
      marsupialization followed by lining the cavity with Surgicel (Ethicon,
      Somerville, NJ) and performance of an omentopexy. RESULTS: Both procedures were
      performed without complication. At 25 months, neither patient showed any evidence
      of symptomatic or radiologic recurrence. Pathology confirmed the preoperative
      diagnoses. CONCLUSIONS: Laparoscopic marsupialization of splenic cysts in
      combination with lining the cyst cavity with Surgicel and omentopexy is a safe,
      feasible, and efficacious method of management with excellent results at 25-month
      follow-up.

PMID- 18049416
TI  - Endovascular management of a splenic artery aneurysm.
AB  - Splenic artery aneurysms represent the third most common aneurysm in the abdomen.
      The majority are asymptomatic and discovered incidentally by abdominal imaging.
      The overall rupture rate is low but the associated mortality rate is high,
      especially in pregnant women and patients with portal hypertension.
      Traditionally, open surgical modalities represented the only viable treatments.
      More recently, laparoscopic and endovascular techniques have been applied to
      these vascular lesions. We report a case of a giant splenic artery aneurysm that
      was diagnosed incidentally and managed successfully by percutaneous splenic
      artery embolization. The case is presented and general considerations regarding
      the presentation, diagnosis, and management of splenic artery aneurysms are
      reviewed.

PMID- 18049417
TI  - Laparoscopic treatment of a wandering spleen causing partial colonic obstruction:
      report of a case.
AB  - Wandering spleens are rarely encountered ectopic localizations of the spleen.
      They are either congenital or acquired owing to the lack of or weakening of the
      major splenic ligaments. Herein, we present a female patient who was admitted to
      our hospital with the complaint of abdominal distension and chronic constipation.
      We performed laparoscopic splenectomy in this case for the diagnosis of a
      wandering spleen located in the right upper quadrant. The accepted treatment of
      this pathology is splenopexy unless there is no necrosis of the organ. Minimal
      invasive procedures should be the primary choice in the treatment of this entity.

PMID- 18049418
TI  - Laparoscopic splenectomy for recurrent splenic cyst after laparoscopic
      marsupialization.
AB  - We describe laparoscopic splenectomy for recurrent splenic cyst after
      laparoscopic marsupialization. The patient was a 24-year-old woman with a 20-cm
      palpable mass in the left upper quadrant. She had undergone laparoscopic
      marsupialization for splenic cyst 62 months previously. Abdominal ultrasonography
      and computed tomography revealed a huge cystic lesion of the spleen, and magnetic
      resonance imaging demonstrated multiple cystic lesions occupying almost the
      entire spleen. We performed laparoscopic splenectomy for the recurrent splenic
      cyst. The operation took 170 minutes. Histologic examination of the resected
      spleen revealed a hemangioma with cyst formation. The cyst wall consisted of
      fibrous tissue, covered by stratified cuboid or squamous epithelium. The patient
      had no abdominal symptoms during 13 months of follow-up. Postoperative follow-up
      examination by ultrasound or computed tomography is required after surgical
      treatment for splenic cyst to exclude the possibility of recurrence after
      preservation of the spleen.

PMID- 18049419
TI  - Retroperitoneoscopic nephrectomy for pelvic kidney.
AB  - The retroperitoneoscopic approach for renal operations is an accepted efficacious
      one. It is, however, significantly less popular than its transperitoneal rival,
      even for small kidneys. We present this case because it magnifies some of the
      advantages of the retroperitoneoscopic approach and because we believe that it is
      probably the approach of choice in this unusual situation.

PMID- 18049420
TI  - Delayed pneumothorax after tubeless percutaneous nephrolithotomy.
AB  - Percutaneous nephrolithotomy is the treatment of choice for large urinary stone
      and staghorn stone. Supracostal access through the upper calyx provides a
      straight tract along the long axis of the kidney and is the optimal route for the
      treatment of staghorn stone. However, the supracostal access bears higher risk
      for pleural or lung injury resulting in hydrothorax or pneumothorax. Percutaneous
      nephrolithotomy induced pneumothorax usually occurs immediately after operation.
      We report a case of delayed pneumothorax after tubeless percutaneous
      nephrolithotomy for a complete staghorn stone.

PMID- 18049421
TI  - Polytetrafluoroethylene prosthesis migration into the bladder after laparoscopic
      hernia repair: a case report.
AB  - Mesh migration after laparoscopic inguinal hernia repair is an unusual and late
      complication. We report a 50-year-old man with persistent painless hematuria and
      urinary infection who underwent bilateral laparoscopic intraperitoneal onlay mesh
      4 years ago. Polytetrafluoroethylene (PTFE) prosthesis was used and fixed with
      tackers. The patient underwent cystoscopy and laparotomy for excision of the
      migrated PTFE prosthesis into the bladder. This is the first case of PTFE
      prosthesis migration into the bladder after laparoscopic hernia repair. We also
      reviewed the literature involving migration of mesh after all inguinal hernial
      repairs.

PMID- 18049422
TI  - The association between HIV infection and alcohol use: a systematic review and
      meta-analysis of African studies.
AB  - To summarize the association between alcohol use and human immunodeficiency virus
      (HIV) infection based on studies conducted in Africa, EMBASE and PubMed were
      searched for African studies that related alcohol use to HIV infection. Meta
      analyses were conducted to obtain pooled univariate and multivariate relative
      risk estimates. Subgroup analyses were performed for studies having different
      sample types: males or females and population-based or high-risk, and ones that
      differentiated between problem and asymptomatic drinkers. Alcohol drinkers were
      more apt to be HIV+ than nondrinkers. The pooled unadjusted odds ratio (OR) from
      20 studies was 1.70 (95% confidence interval, CI = 1.45-1.99). Results from 11
      studies that adjusted for other risk factors produced a pooled risk estimate of
      1.57 (95% CI = 1.42-1.72). Males and females had similar risk estimates, while
      studies involving high-risk samples tended to report larger pooled odds ratios
      than studies of the general population. When compared with nondrinkers, the
      pooled estimates of HIV risk were 1.57 (95% CI = 1.33-1.86) for non-problem
      drinkers versus 2.04 (95% CI = 1.61-2.58) for problem drinkers, a statistically
      significant difference (z = 2.08, P <0.04). Alcohol use was associated with HIV
      infection in Africa and alcohol-related interventions might help reduce further
      expansion of the epidemic.

PMID- 18049423
TI  - Preventing unintended pregnancy and HIV transmission: dual protection or dual
      dilemma?

PMID- 18049424
TI  - Comparing prevalence of condom use among 15,379 female sex workers injecting or
      not injecting drugs in China.
AB  - OBJECTIVES: To compare the prevalence of condom use with clients and regular sex
      partners between female sex workers (FSWs) who were or were not injecting drug
      users (IDUs). METHODS: Behavioral surveillance data (2002-2004) conducted in
      Sichuan, China were analyzed. Mapping exercises were done. About 250 to 400 FSWs
      were anonymously interviewed from selected establishments in 19 surveillance
      sites. RESULTS: Of all 15,379 FSWs studied, 3.2% were IDUs. This group, when
      compared with the non-IDU group, was less likely to have used condoms with
      clients (last episode: 71.1% vs. 81.2%, OR = 0.6, P < 0.01; consistent use in the
      last month: 26.7% vs. 40.4%, OR = 0.5, P < 0.01) or to possess a condom (68.7%
      vs. 77.8%, OR = 0.6, P < 0.01). The between-group difference in last month's
      consistent condom use with clients remained significant in the multivariate
      analyses, after adjusting for other significant factors [age, education level,
      age at first sex, having a regular sex partner, HIV-related knowledge and
      perceptions, HIV antibody testing (OR = 1.1-2.9, P < 0.05); STD symptoms, type of
      sex workers, longer duration of sex work, larger number of clients per week, and
      not having received HIV-related information (OR = 0.4-0.9)]. Comparable results
      were obtained for condom use with the last client. Such between-group differences
      were, however, not observed for condom use with regular sex partners (P > 0.05).
      Exposure to HIV-related services was associated with condom use with clients (OR
      = 1.3-2.8, P < 0.05). CONCLUSIONS: Higher sexual risk behaviors were found among
      FSWs who were also IDUs, when compared with those who were non-IUDs. A double
      risk bridging population for HIV transmission thereby exists.

PMID- 18049425
TI  - Herpes simplex virus-2 and HIV among noninjecting drug users in New York city.
AB  - OBJECTIVE: To examine the relationship between herpes simplex virus 2 (HSV-2)
      seroprevalence and human immunodeficiency virus (HIV) seroprevalence among
      noninjecting heroin and cocaine users in New York City. METHODS: Four hundred
      sixty-two noninjecting cocaine and heroin users were recruited from a drug
      detoxification program in New York City. Smoking crack cocaine, intranasal use of
      heroin, and intranasal use of cocaine were the most common types of drug use. A
      structured interview was administered and a serum sample was collected for HIV
      and HSV testing. RESULTS: HIV prevalence was 19% (95% CI 15%-22%) and HSV-2
      seroprevalence was 60% (95% CI 55%-64%). The adjusted risk ratio for the
      association between HSV-2 and HIV was 1.9 (95% CI 1.21%-2.98%). The relationship
      between HSV-2 and HIV was particularly strong among females, among whom 86% were
      HSV-2 seropositive, 23% were HIV seropositive, and all HIV seropositives were
      also HSV-2 seropositive. CONCLUSIONS: HSV-2 appears to be an important factor in
      sexual transmission of HIV among noninjecting cocaine and heroin users in New
      York City, especially among females. The estimated population attributable risk
      for HIV infection attributable to HSV-2 infection in this sample was 38%.
      Programs to manage HSV-2 infection should be developed as part of comprehensive
      HIV prevention for noninjecting drug users.

PMID- 18049426
TI  - Evaluation of hawthorn extract on immunomodulatory biomarkers in a pressure
      overload model of heart failure.
AB  - BACKGROUND: Hawthorn extract (Crataegeus sp.) a botanical complementary and
      alternative medicine is often used to treat heart failure. The mechanism(s) by
      which hawthorn extract may treat heart failure is unknown but may include,
      theoretically, immunological effects. Therefore, the purpose of this study is to
      determine the effect of hawthorn extract on the immunomodulatory response in a
      pressure overload model of heart failure. MATERIAL/METHODS: A total of 62 male
      Sprague-Dawley rats were randomized to either aortic constriction + vehicle (AC;
      n=15), aortic constriction + hawthorn 1.3 mg/kg (HL, n=17), aortic constriction +
      hawthorn 13 mg/kg (HM, n=15), or aortic constriction + hawthorn 130 mg/kg (HH,
      n=15). Six months after surgical procedure animals were sacrificed and plasma
      samples obtained for the measurement of the following immunomodulatory markers:
      interleukin (IL) IL-1ss, IL-2, IL-6, IL-10; and leptin. RESULTS: The mortality
      rate following 6 months of aortic constriction was 40% in the AC group compared
      to 41%, 60%, and 53% for the HL, HM, and HH groups respectively (P>0.05 compared
      to AC). Aortic constriction produced a similar increase in the left
      ventricle/body weight ratio for all groups. Hawthorn extract had no effect on the
      immunomodulatory markers measured in this study, although there appeared to be a
      trend suggesting suppression of IL-2 plasma concentrations. CONCLUSIONS: In this
      animal model of heart failure, hawthorn extract failed to significantly affect
      the immunomodulatory response characterized after 6 months of pressure overload
      at a time when approximately 50% mortality was exhibited. Mechanisms other than
      immunological may better define hawthorn's effect in treating heart failure.

PMID- 18049427
TI  - The role of osteoactivin-derived peptides in osteoblast differentiation.
AB  - BACKGROUND: In our previous studies, we found that osteoactivin (OA) plays an
      important role in the regulation of osteoblast differentiation in vitro. Our
      studies also suggested that the region of OA protein that contains an RGD motif
      might play a vital role in the function of OA in osteoblast differentiation. In
      this study, we examined the functional role of OA-derived peptide containing the
      RGD motif (OA-D) in osteoblast differentiation. MATERIAL/METHODS: For this
      purpose, we designed another peptide, termed OA-E, that has sequence similar to
      OA-D but with glutamic acid (E) instead of aspartic acid (D). The effect of OA-E
      peptide on osteoblast differentiation was examined. Interestingly, OA-E peptide
      induced osteoblast differentiation in a manner similar to OA-D peptide. These
      data suggested that the effect of OA-derived peptides is RGD independent and it
      could be dependent on other features in the amino acid sequence of these
      peptides. RESULTS: OA-D peptide treatment markedly induced osteoblast
      differentiation markers in vitro compared to cultures treated with negative
      control peptide (NCP). Interestingly, OA-E peptide induced osteoblast
      differentiation in a manner similar to OA-D peptide. These data suggested that
      the effect of OA-derived peptides is RGD independent and it could be dependent on
      other features in the amino acid sequence of these peptides. Since
      phosphorylation of amino acid residues in proteins and peptides plays a major
      role in biological systems, the phosphorylation pattern of amino acid sequences
      of OA-derived peptides and OA protein family members were examined using
      bioinformatic analysis tools. We found that OA-derived peptides and OA protein
      family members have serine residue, close to c-terminus and might be
      phosphorylated with casein kinase II. Casein kinase II is known to phosphorylate
      many osteoblast-related proteins that regulate osteoblast development and
      differentiation such as osteopontin and vitronectin. CONCLUSIONS: Collectively,
      these data showed that both OA-D and OA-E peptides significantly induced
      osteoblast differentiation in vitro and that effect is RGD independent.

PMID- 18049428
TI  - Protective effect of lysozyme chloride on gastric oxidative stress and
      hemorrhagic ulcers in severe atherosclerotic rats.
AB  - BACKGROUND: Calcium and cholesterol play major roles in the formation of
      atherosclerosis. Whether severe atherosclerosis induced by co-administration of a
      mixture containing vitamin D2 (vit D2) and cholesterol can result in gastric
      hemorrhagic damage is unknown. Gastric oxidative stress and hemorrhagic
      ulceration in rats with atherosclerosis induced by co-administration of vit D2
      and cholesterol and the protective effect of lysozyme chloride on this ulcer
      model were investigated. MATERIAL/METHODS: Male Wistar rats were challenged
      intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vit
      D2 and cholesterol to induce atherosclerosis. Control rats received the same
      volume of corn oil only. After 24-h fasting followed by gastric surgery, the rat
      stomachs were irrigated for 3 h with simulated rat gastric juice or normal
      saline. Various gastric mucosal ulcerogenic factors (acid back-diffusion, lipid
      peroxides, histamine concentration, and hemorrhagic ulcers) and defensive
      substances (mucosal glutathione and mucus secretion) were determined. RESULTS:
      Augmentation of serum calcium concentration, total cholesterol, and low-density
      lipoprotein was observed in atherosclerotic rats. Greater mucosal ulcerogenic
      parameters and lower defensive substances were achieved in these rats. High
      correlation between decreased mucosal glutathione and ulceration as well as
      between increased mucosal lipid peroxide levels and ulceration was also found in
      the atherosclerotic rats. Daily intragastric lysozyme chloride dose-dependently
      protected gastric mucosal hemorrhagic damage in the atherosclerotic rats.
      CONCLUSIONS: Atherosclerosis induced by co-administration of vit D2 and
      cholesterol could produce gastric oxidative stress and hemorrhagic ulcer that was
      ameliorated by lysozyme chloride in rats.

PMID- 18049429
TI  - CD30 (Ber-H2) expression by thymocytes and thymic epithelial cells during the
      late first and second trimester of gestation: an immunohistochemical and in situ
      hybridization (ISH) study.
AB  - BACKGROUND: The exact biological function of CD30 in the thymus during
      development has been only partially elucidated, although data indicate it may be
      involved in negative selection. This study was prompted by the observation of a
      positive reaction of thymic epithelial cells (TECs), Hassall's corpuscles, and
      thymocytes with the monoclonal antibody CD30 during the late first and second
      trimester. MATERIAL/METHODS: Twenty paraffin-embedded fetal thymus specimens at
      the late first and second trimester were investigated by conventional histology
      and immunohistology for CD30 expression. To provide additional information on the
      nature and localization of CD30+ thymocytes and CD30+ TECs, in situ hybridization
      (ISH) was performed on the specimens. RESULTS: 1) In the medulla, a statistically
      significant difference between CD30+ thymocytes from the late first trimester and
      those from the second trimester (p<0.0001, t-test) was demonstrated. No
      significant difference was found concerning CD30+ thymocytes in the cortex. 2)
      Many medullary TECs and Hassall's corpuscles showed high expression of CD30
      during the second trimester, whereas small numbers of CD30+ TECs were found
      during the late first trimester. No statistically significant difference was
      found concerning CD30+ TECs in the cortex. CD30 was expressed by ISH in many
      cells in the medulla and along the septa, whereas the cortex showed little if any
      expression. Accordingly, a higher CD30 expression was found in medullary than in
      cortical thymocytes. CONCLUSIONS: Comparison of CD30 expression by TECs and
      thymocytes during the late first trimester and second trimester suggests an
      important role for CD30 in thymic selection.

PMID- 18049430
TI  - Effect of turmeric and curcumin on oxidative stress and antioxidant enzymes in
      streptozotocin-induced diabetic rat.
AB  - BACKGROUND: There is increasing evidence that complications related to diabetes
      are associated with increased oxidative stress. Curcumin, an active principle of
      turmeric, has several biological properties, including antioxidant activity. The
      protective effect of curcumin and turmeric on streptozotocin (STZ)-induced
      oxidative stress in various tissues of rats was studied. MATERIAL/METHODS: Three
      month-old Wistar-NIN rats were made diabetic by injecting STZ (35 mg/kg body
      weight) intraperitoneally and fed either only the AIN-93 diet or the AIN-93 diet
      containing 0.002% or 0.01% curcumin or 0.5% turmeric for a period of eight weeks.
      After eight weeks the levels of oxidative stress parameters and activity of
      antioxidant enzymes were determined in various tissues. RESULTS: STZ-induced
      hyperglycemia resulted in increased lipid peroxidation and protein carbonyls in
      red blood cells and other tissues and altered antioxidant enzyme activities.
      Interestingly, feeding curcumin and turmeric to the diabetic rats controlled
      oxidative stress by inhibiting the increase in TBARS and protein carbonyls and
      reversing altered antioxidant enzyme activities without altering the
      hyperglycemic state in most of the tissues. CONCLUSIONS: Turmeric and curcumin
      appear to be beneficial in preventing diabetes-induced oxidative stress in rats
      despite unaltered hyperglycemic status.

PMID- 18049431
TI  - Insulin treatment reduces pre-prandial plasma ghrelin concentrations in children
      with type 1 diabetes.
AB  - BACKGROUND: Ghrelin is well recognized as a key factor in regulating appetite and
      energy homeostasis. The aim of the present study is to characterize the plasma
      ghrelin concentrations in children with type 1 diabetes at the time of diagnosis
      and to determine the effect of metabolic control after insulin therapy on
      circulating ghrelin levels. Also, the relationship between the simultaneous blood
      glucose concentrations and fasting plasma ghrelin concentrations was explored.
      MATERIAL/METHODS: This prospective study assessed the changes in pre-prandial
      plasma ghrelin levels after treatment of type 1 diabetes with insulin. RESULTS:
      The study comprised 19 children with new onset diabetes mellitus. Mean plasma
      ghrelin levels declined by 29% in diabetic children post insulin treatment
      (p=0.007). There was a significant correlation between plasma ghrelin and body
      mass index (BMI) in children with type 1 diabetes at diagnosis (r=-0.54), but not
      at follow up. The difference in ghrelin at diagnosis and at 3 month follow up
      demonstrated an inverse relationship to difference in plasma glucose (r=-0.48).
      CONCLUSIONS: Plasma ghrelin concentrations could be suppressed in untreated type
      1 diabetic children by improved glycemic control following insulin replacement.

PMID- 18049432
TI  - Association of angiotensin-converting enzyme/DD genotype with sarcoidosis
      susceptibility in Slovenian patients.
AB  - BACKGROUND: Sarcoidosis is a multisystemic chronic inflammatory disorder of
      unknown etiology with multifactorial genetic predisposition. An elevated ACE
      serum level is considered to be the activity marker of the disease. The
      involvement of the ACE I/D polymorphism in sarcoidosis susceptibility has been
      investigated in different populations, but results have been inconclusive. The
      purpose of this study was to evaluate the possible association of angiotensin
      converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism with
      sarcoidosis in the Slovene population. MATERIAL/METHODS: In 105 sarcoidosis
      patients (69 female, 36 male, mean age: 41+/-1 years) and in 80 sex- and age
      matched control subjects, genotyping for the ACE gene I/D polymorphism was
      performed by PCR and restriction enzyme digestion. RESULTS: An increased
      frequency of DD homozygotes vs. II homozygotes + ID heterozygotes was found in
      the group of sarcoidosis patients compared with the control group (OR: 2.19,
      95%CI: 1.12-4.26, p=0.02). No differences in genotype frequencies were found in
      the group of sarcoidosis patients when considering the clinical course or
      presentation of the disease. CONCLUSIONS: These results indicate that the ACE
      gene I/D polymorphism might be a risk factor for sarcoidosis susceptibility in
      the Slovene population and imply the possible role of population origin in the
      modulation of the influence of ACE gene variability in the pathophysiology of
      sarcoidosis.

PMID- 18049433
TI  - Alcohol craving, limbic irritability, and stress.
AB  - BACKGROUND: Recent findings indicate that craving during alcohol withdrawal, also
      in abstinent patients, can relate to kindling phenomena caused by sensitization
      in temporo-limbic structures. Because limbic structures are involved in stress,
      anxiety, and emotional processing, kindling and temporolimbic seizure-like
      activity are also closely related to various psychiatric symptoms frequently
      presented without seizure disorders. Recent findings also show that these seizure
      like processes are related to limbic irritability, which may also be
      significantly influenced by stressful life events. MATERIAL/METHODS: The
      hypothesis tested in the present study is that limbic irritability could be
      closely related to craving symptoms. Therefore, limbic irritability and craving
      were assessed using psychometric measures in 40 alcohol-dependent patients and
      the results were compared with those of 40 healthy controls. RESULTS: Statistical
      analysis showed highly significant correlation (r=0.75, p<0.0000001) between
      limbic irritability (LSCL-33) and craving (ACQ-R) and highly increased limbic
      irritability scores in the patients compared with the healthy controls.
      CONCLUSIONS: The results indicate that craving symptoms are related to the
      kindling process presented in the form of cognitive, affective, sensory, somatic,
      behavioral, and memory symptoms linked to limbic irritability and temporo-limbic
      seizure-like activity.

PMID- 18049434
TI  - Changes in intra-abdominal pressure and central venous and brain venous blood
      pressure in patients during extracorporeal circulation.
AB  - BACKGROUND: The aim was to analyze IAP changes and the relationships between IAP,
      CVP, and brain venous blood pressure, which are still unknown, in patients
      undergoing coronary artery bypass grafting (CABG) with extracorporeal
      circulation. MATERIAL/METHODS: Twenty-five male patients (aged 53-67 years)
      underwent CABG under general anesthesia with normovolemic hemodilution. IAPs were
      measured in the urinary bladder, CVP by left internal jugular vein cannulation,
      and brain venous blood pressure by retrograde cannulation of the right jugular
      vein bulb (JVP, jugular vein pressure) at seven time-points: 1) after induction
      of anesthesia before the operation, 2) during internal thoracic artery
      preparation, 3) 10 minutes after heart-lung machine disconnection, 4) after
      procedure completion, before sending the patient to the intensive postoperative
      care unit, 5) one hour after the procedure, 6) 6 hours after the procedure, and
      7) 18 hours after the procedure. RESULTS: IAP increased from points 3 to 6. CVP
      increased from points 3, 4, and 5 and decreased at point 7. Similar changes were
      noted in JVP. There were significant correlations between IAP and CVP at points
      1, 2, 3, 4, and 5, IAP and JVP at points 3, 4, and 5, and CVP and JVP at all
      points. The overall analysis showed correlations between IAP and CVP and JVP and
      very strong correlation between CVP and JVP. CONCLUSIONS: 1) CABG with
      extracorporeal circulation resulted in increases in IAP, CVP, and brain venous
      blood pressure. 2) The changes in CVP and brain venous blood pressure correlated
      with intra-abdominal pressure.

PMID- 18049435
TI  - The effect of Nigella sativa L. (black cumin seed) on intractable pediatric
      seizures.
AB  - BACKGROUND: Despite the availability and use of numerous antiepileptic drugs
      (AEDs), nearly 15% of childhood epilepsy cases are resistant to treatment.
      However, in traditional medicine, Nigella Sativa L. ("black cumin seed") has been
      known for its anticonvulsant effects. This plant is naturally distributed in Iran
      and has been widely used as a natural remedy for a long time. In this study the
      efficacy of this agent in reducing the frequency of seizures in childhood
      refractory epilepsy was assessed. MATERIAL/METHODS: In this double-blinded
      crossover clinical trial conducted on children with refractory epilepsy, the
      aqueous extract of black seed was administered as an adjunct therapy and the
      effects were compared with those of a placebo. Twenty-three children were entered
      in the study and 20 remained in the study (13 months to 13 years old, 10 boys and
      10 girls). All patients were receiving constant treatment for at least one month
      before the study. They received extract (40 mg/kg/8 h) or placebo for a period of
      four weeks and between these periods for two weeks they received only their pre
      existing anti-epileptic drugs (AEDs). RESULTS: The mean frequency of seizures
      decreased significantly during treatment with extract (p<0.05). CONCLUSIONS: It
      can be concluded that the water extract of Nigella sativa L. has antiepileptic
      effects in children with refractory seizures.

PMID- 18049436
TI  - Biochemical changes after a qigong program: lipids, serum enzymes, urea, and
      creatinine in healthy subjects.
AB  - BACKGROUND: The aim of the present study was to analyze the effects of a qigong
      training program on blood biochemical parameters. MATERIAL/METHODS: Twenty-nine
      healthy subjects participated in the study of whom 16 were randomly assigned to
      the experimental group and 13 to the control. The experimental subjects underwent
      daily qigong training for one month. Blood samples for the quantification of
      biochemical parameters (total cholesterol, HDL, LDL, triglycerides,
      phospholipids, GOT, GPT, GGT, urea, creatinine) were taken before and after the
      training program. As statistical analysis, ANCOVA was performed. RESULTS:
      Statistically significant differences were found showing that the experimental
      group had lower serum levels of GOT (glutamic-oxaloacetic transaminase), GPT
      (glutamic-pyruvic transaminase), and urea and that there was a trend towards
      significance in GGT (gamma-glutamyltransferase). CONCLUSIONS: This study
      demonstrates that after practicing qigong for the short period of one month,
      noteworthy changes in several blood biochemical parameters were induced. While it
      is tempting to speculate on the relevance and implications of these biochemical
      variations, further investigation is needed to elucidate the scope of these
      findings.

PMID- 18049437
TI  - Is there any relationship between streptococcal infection and multiple sclerosis?
AB  - BACKGROUND: Multiple sclerosis (MS) is an immune-mediated inflammatory
      demyelinating disease of uncertain etiology. Although the mechanisms of inducting
      autoimmunity by some of the infectious agents have been investigated, there is
      not yet enough research on streptococcal infections. MATERIAL/METHODS: To
      understand the effect of past group A streptococcal infection on MS,
      antistreptolysin O (ASO) and antideoxyribonuclease B (ADNase B) were measured in
      21 patients with relapsing-remitting MS and 21 healthy blood donors by
      nephelometric assay. RESULTS: ADNase B levels in the patients with MS were found
      to be significantly higher than in the controls (p<0.001); however, ASO levels
      were similar in both groups. CONCLUSIONS: These findings indicate that a
      relationship between multiple sclerosis and streptococcal infections may exist,
      but to acquire a better understanding of the role of group A streptococci in the
      pathogenesis of multiple sclerosis, more studies with animal models are
      necessary.

PMID- 18049438
TI  - Low-grade inflammation in white-coat hypertension.
AB  - BACKGROUND: C-reactive protein (CRP), a marker of systemic low-grade
      inflammation, is frequently elevated in essential hypertension and predicts
      cardiovascular prognosis independently of conventional risk factors. The risk
      profile of white-coat hypertension is not yet completely clear. The aim of this
      study was to determine the levels of high-sensitivity CRP (hs-CRP) in white-coat
      hypertensive subjects. MATERIAL/METHODS: Thirty-six age-, sex-, and body mass
      index-matched white-coat hypertensive subjects, 36 essential hypertensive
      patients, and 36 normotensive subjects were included in the study. RESULTS: Hs
      CRP levels were significantly higher in the essential hypertensive and white-coat
      hypertensive groups than in the normotensive group (0.66+/-0.29, 0.47+/-0.32, and
      0.27+/-0.22 mg/dl, respectively, p<0.001). It was also higher in the essential
      hypertensive group than in the white-coat hypertensive group (p=0.014).
      CONCLUSIONS: Our data show that patients with white-coat hypertension have higher
      hs-CRP levels than normotensive patients and this may be an indication of
      increased risk.

PMID- 18049439
TI  - The role of echocardiography and its comparison with NT-proBNP measurements in
      patients with acute myocardial infarction.
AB  - BACKGROUND: This study investigated the use of echocardiography in the early
      detection of regional wall motion abnormalities (RWMA) in patients presenting
      with acute myocardial infarction (AMI). The relationship between RWMA and
      mechanical complications, as assessed by two-dimensional echocardiography, and
      admission levels of amino terminal fragment of pro-brain natriuretic peptide (NT-
      proBNP) was also examined. MATERIAL/METHODS: The study population comprised 226
      patients admitted to hospital with a diagnosis of AMI. Echocardiography and NT
      proBNP measurements were performed on all patients. RESULTS: Sixty-eight percent
      of the patients with AMI were found to have RWMA on echocardiography.
      Significantly more patients had RWMA within any given range of ejection fraction
      (EF) (p<0.001), but this difference was most pronounced in those with left
      ventricular (LV) dysfunction. Mitral regurgitation was the most common
      complication (48%) seen on echocardiography. The majority of patients (84%) had
      elevated NT-proBNP levels on admission; this was evident in all categories of EF
      (p=0.003). In those with normal EF on echocardiography (58%), more patients had
      elevated levels regardless of the presence of RWMA. CONCLUSIONS: This study
      showed that echocardiography is useful in the detection of RWMA in the early
      stages of AMI. No significant relationship was demonstrated between NT-proBNP
      levels and RWMA in patients with normal or abnormal LV function. Admission plasma
      NT-proBNP may, however, be considered as an additional marker in the diagnosis of
      AMI, especially in those without RWMA.

PMID- 18049440
TI  - The effects of medical treatment and rehabilitation in a patient with adult
      tethered cord syndrome in the late postoperative period.
AB  - BACKGROUND: The possibility of functional tethered cord syndrome (TCS) should be
      considered when adolescent patients present with unexplained lumbar, buttock, and
      leg symptoms. Symptoms progress if untreated. Success depends on early diagnosis,
      the complete untethering of the spinal cord, and rehabilitation. A rare case of
      adult TCS is reported. CASE REPORT: A 42-year-old female patient with lower back
      and leg pain, severe flexor reflex responses, and a walking disorder was
      evaluated. Gabapentin and tizanidine were given to treat the neuropathic pain and
      flexor reflex responses. An exercise program was applied to improve the walking
      disorder. Finally, the patient's complaints of pain considerably decreased,
      flexor reflex responses were reduced, and a more comfortable walking motion was
      observed. CONCLUSIONS: A rehabilitative approach is very important and a
      multidisciplinary follow-up and treatment procedure is required in the clinical
      healing process of all patients presenting with a tethered cord condition,
      whether surgical intervention is carried out or not.

PMID- 18049441
TI  - Paraganglioma of the larynx: a case report.
AB  - BACKGROUND: Paragangliomas arise from paraganglion cells as part of the diffuse
      neuroendocrine system. These tumors are generally considered benign. They appear
      rarely in the larynx and most of them are supraglottic. CASE REPORT: We present
      the case of a 45-year-old female patient who presented with a history of
      hoarseness for two months and difficulties in swallowing for twenty days.
      Fiberoptic endoscopic examination showed a submucosal mass involving the left
      side of the larynx. The subglottic area of the larynx was normal as were the base
      of the tongue and pharynx. The mobility of the true vocal cords was normal. There
      was no stridor or signs of airway obstruction and no neck lemphadenopathy. The
      patient underwent a direct microlaryngoscopy under general anesthesia. The tumor
      was entirely removed along with the left aryepiglottic fold with respect to the
      surrounding tissues. Histopathological examination showed a benign laryngeal
      paraganglioma. CONCLUSIONS: Paragangliomas of the larynx are rare neuroendocrine
      tumors. Most of them are supraglottic. The differential diagnosis of laryngeal
      paraganglioma includes typical carcinoid, atypical carcinoid, small-cell
      neuroendocrine carcinoma, malignant melanoma, and medullary carcinoma of the
      thyroid gland. Although these tumors are generally considered benign, their
      surgical removal with respect to the surrounding tissues and maximal possible
      preservation of laryngeal function is the treatment of choice.

PMID- 18049442
TI  - Effects of Yoga and an Ayurveda preparation on gait, balance and mobility in
      older persons.

PMID- 18049443
TI  - Piezosurgery in the excision of middle-ear tumors: effects on mineralized and non
      mineralized tissues.
AB  - BACKGROUND: Piezosurgery is a new instrument able to cut bone without necrosis
      and non-mineralized tissue damage. The aim of this study was to test the
      Piezosurgery as a new and alternative method for the excision of middle-ear
      tumors and to analyze its effects on soft tissues. MATERIAL/METHODS: The
      Piezosurgery device was used to excise eight glomus tympanicum tumors and two
      primary B-cell lymphomas of the middle ear. The piezoelectric device uses low
      frequency ultrasonic waves (24.7-29.5 kHz); the applied power can be modulated
      between 2.8 and 16 W and is programmed in accordance to the density of the bone.
      The equipment consists of two hand-pieces, two inserts, and two peristaltic
      pumps. The microvibrations that are created in the piezoelectric hand-piece cause
      the inserts to vibrate linearly by between 60 and 210 microm. RESULTS:
      Piezosurgery provided excellent control in all the patients, without bleeding and
      harmful effects on the adjacent structures of the middle and inner ear.
      CONCLUSIONS: Piezosurgery is a new and revolutionary osteotomy technique
      utilizing the microvibrations of scalpels at ultrasonic frequency, so that soft
      tissue will not be damaged even upon accidental contact with the cutting tip. The
      vibration frequency of Piezosurgery is optimal for mineralized tissue and does
      not cut the adjacent soft tissue, minimizing the risk of harming the adjacent
      tissues. This renders the piezoelectric device ideal for application at the
      border between hard and soft tissues as in the excision of a middle-ear tumor.

PMID- 18049444
TI  - Mandatory neonatal male circumcision in Sub-Saharan Africa: medical and ethical
      analysis.
AB  - The majority of those infected with HIV in sub-Saharan Africa do not have access
      to antiretroviral therapy, which is known to prolong the lives of HIV-positive
      persons in industrialized countries. Although the availability of antiretroviral
      therapy for those infected with HIV has increased worldwide, the infection rate
      out surpasses those started on such treatment. Without an AIDS vaccine or
      curative treatment, and given the difficulty in getting persons at risk to adopt
      healthy sexual behaviors, alternative approaches to decrease the spread of HIV
      infection are urgently needed. Three recent randomized controlled trials
      undertaken in Kisumu, Kenya, Raki District, Uganda and Orange Farm, South Africa
      have confirmed that male circumcision reduces the risk of heterosexually acquired
      HIV infection in men by approximately 51% to 60%. These three studies provide a
      solid evidence-base for future health policy. The procedure for adolescents and
      adults is expensive compared to abstinence, condoms or other methods; and the
      surgery is not without serious risks if performed by traditional healers using
      unsterilized blades as often happens in rural Africa. However, neonatally, the
      procedure is relatively inexpensive and the risks diminish considerably.
      Mandating neonatal male circumcision is an effective therapy that has minimal
      risks, is cost efficient and will save human lives. To deny individuals access to
      this effective therapy is to deny them the dignity and respect all persons
      deserve. Neonatal male circumcision is medically necessary and ethically
      imperative.

PMID- 18049445
TI  - Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade
      systemic inflammation.
AB  - Plasma levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha,
      and lipid peroxides are high whereas those of endothelial nitric oxide are low in
      insulin resistance, obesity, type 2 diabetes mellitus, hypertension,
      hyperlipidemias, metabolic syndrome X, and Alzheimer's disease suggesting that
      these diseases are characterized by low-grade systemic inflammation. Recent
      studies showed that the plasma and tissue activities of enzymes
      butyrylcholinesterase and acetylcholinesterase are elevated in patients with
      Alzheimer's disease, and diabetes mellitus, hypertension, insulin resistance, and
      hyperlipidemia. As a result of this increase in the activities of enzymes
      acetylcholinesterase and butyrylcholinesterase, the plasma and tissue levels of
      acetylcholine (ACh) will be low. The "cholinergic anti-inflammatory pathway"
      mediated by acetylcholine acts by inhibiting the production of tumor necrosis
      factor, interleukin-1, macrophage migration inhibitory factor, and high mobility
      group box-1 and suppresses the activation of nuclear factor-kappa B expression.
      ACh is a neurotransmitter and regulates the levels and activities of serotonin,
      dopamine and other neuropeptides and thus, modulates both immune response and
      neurotransmission. Hence, both acetylcholinesterase and butyrylcholinesterase by
      inactivating acetylcholine may enhance inflammation. This suggests that increased
      plasma and tissue activities of acetylcholinesterase and butyrylcholinesterase
      seen in various clinical conditions could serve as a marker of low-grade systemic
      inflammation.

PMID- 18049446
TI  - Persistence of evolutionary memory: primordial six-transmembrane helical domain
      mu opiate receptors selectively linked to endogenous morphine signaling.
AB  - Biochemical, molecular and pharmacological evidence for two unique six
      transmembrane helical (TMH) domain opiate receptors expressed from the micro
      opioid receptor (MOR) gene have been shown. Designated micro3 and micro4
      receptors, both protein species are Class A rhodopsin-like members of the
      superfamily of G-protein coupled receptors but are selectively tailored to
      mediate the cellular regulatory effects of endogenous morphine and related
      morphinan alkaloids via stimulation of nitric oxide (NO) production and release.
      Both micro3 and micro4 receptors lack an amino acid sequence of approximately 90
      amino acids that constitute the extracellular N-terminal and TMH1 domains and
      part of the first intracellular loop of the micro1 receptor, but retain the
      empirically defined ligand binding pocket distributed across conserved TMH2,
      TMH3, and TMH7 domains of the micro1 sequence. Additionally, the receptor
      proteins are terminated by unique intracellular C-terminal amino acid sequences
      that serve as putative coupling or docking domains required for constitutive NO
      synthase activation. Because the recognition profile of micro3 and micro4
      receptors is restricted to rigid benzylisoquinoline alkaloids typified by
      morphine and its extended family of chemical congeners, it is hypothesized that
      conformational stabilization provided by interaction of extended extracellular N
      terminal protein domains and the extracellular loops is required for binding of
      endogenous opioid peptides as well as synthetic flexible opiate alkaloids.

PMID- 18049447
TI  - Loss-of-function mutations in the filaggrin gene and allergic contact
      sensitization to nickel.
AB  - Allergic contact dermatitis is one of the most frequent dermatological problems
      affecting 7% of the general population. Impaired skin barrier function
      facilitates the penetration of contact allergens and irritants into the epidermal
      layer and is regarded as an important cofactor promoting the process of allergic
      contact sensitization. Filaggrin is crucial for the maintenance of the skin
      barrier function. Loss-of-function mutations within the filaggrin (FLG) gene are
      associated with skin barrier diseases such as ichthyosis vulgaris and atopic
      eczema (AE). To assess the impact of FLG on allergic contact sensitization and
      plausible intermediate traits, the two prevalent FLG mutations R501X and 2282del4
      were typed in 1,502 individuals of the KORA C population-based cohort with
      extensive dermatologic phenotyping. Associations of FLG mutations with AE could
      be replicated. Strong associations were seen with dry skin, palmar
      hyperlinearity, and keratosis pilaris. In addition, an association with contact
      sensitization to nickel and contact sensitization to nickel combined with
      intolerance to fashion jewelry, but not with other contact allergens, was
      observed. From these data, we conclude that a genetically determined FLG
      deficiency manifests as dry skin and features of ichthyosis vulgaris. In
      addition, FLG deficiency may also represent a risk factor for contact
      sensitization to allergens.

PMID- 18049448
TI  - Propionibacterium acnes stimulates pro-matrix metalloproteinase-2 expression
      through tumor necrosis factor-alpha in human dermal fibroblasts.
AB  - Propionibacterium acnes (P. acnes) is a commensal microorganism found in sebum
      rich skin and plays a role in acne inflammation by stimulating keratinocyte to
      produce a number of proinflammatory cytokines. However, the role of P. acnes in
      the dermis of acne lesions, where tissue remodeling after inflammation eventually
      takes place, is not known. In this study, we investigated whether P. acnes
      induces matrix metalloproteinase (MMP), a key enzyme involved in matrix
      remodeling in human dermal fibroblasts (hDF). We found that P. acnes increased
      expression of pro-matrix metalloproteinase (proMMP)-2 mRNA/protein in hDF, but
      not that of proMMP-9. Concomitantly, P. acnes induced tumor necrosis factor-alpha
      (TNF-alpha) mRNA/protein expression in hDF, which in turn increases both proMMP-2
      mRNA and protein expression. P. acnes induced such changes through the activated
      NF-kappaB pathway. Doxycycline was found to inhibit the expression of proMMP-2
      induced either by P. acnes or TNF-alpha. These results suggest that P. acnes
      stimulates hDF to produce TNF-alpha, which mediates the expression of proMMP-2
      through the NF-kappaB pathway. The secretion of proMMP-2 from hDF upon P. acnes
      stimulation may contribute to the pathogenesis of tissue remodeling in acne skin.

PMID- 18049449
TI  - KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to
      TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome.
AB  - Naegeli-Franceschetti-Jadassohn syndrome (NFJS) is a rare autosomal dominant
      disorder characterized by loss of dermatoglyphics, reticulate hyperpigmentation
      of the skin, palmoplantar keratoderma, abnormal sweating, and other developmental
      anomalies of the teeth, hair, and skin. We recently demonstrated that NFJS is
      caused by heterozygous nonsense or frameshift mutations in the E1/V1-encoding
      region of KRT14, but the mechanisms for their deleterious effects in NFJS remain
      elusive. In this study, we further expand the spectrum of NFJS-causing mutations
      and demonstrate that these mutations result in haploinsufficiency for keratin 14
      (K14). As increased apoptotic activity was observed in the epidermal basal cell
      layer in NFJS patients and as previous data suggested that type I keratins may
      confer resistance to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in
      epithelial tissues, we assessed the effect of down-regulation of KRT14 expression
      on apoptotic activity in keratinocytes. Using a HaCaT cell-based assay, we found
      that decreased KRT14 expression is associated with increased susceptibility to
      TNF-alpha-induced apoptosis. This phenomenon was not observed when cells were
      cultured in the presence of doxycycline, a known negative regulator of TNF-alpha
      dependant pro-apoptotic signaling. Collectively, our results indicate that NFJS
      results from haploinsufficiency for K14 and suggest that increased susceptibility
      of keratinocytes to pro-apoptotic signals may be involved in the pathogenesis of
      this ectodermal dysplasia syndrome.

PMID- 18049450
TI  - Polymorphisms of TP53 Arg72Pro, but not p73 G4C14>A4TA4 and p21 Ser31Arg,
      contribute to risk of cutaneous melanoma.

PMID- 18049451
TI  - The epidermal growth factor receptor system in skin repair and inflammation.
AB  - The epidermal growth factor (EGF) family comprises multiple mediators such as
      transforming growth factor-alpha, amphiregulin, heparin binding-EGF, and
      epiregulin, which are crucially involved in the tissue-specific
      proliferation/differentiation homeostasis. Typically, they act in an autocrine
      and paracrine manner on their specific cell membrane receptor and mount an
      effective reparative response to any attack to biophysical integrity. In
      addition, the EGFR can be activated by transactivation from a variety of G
      protein-coupled receptors, integrins, and cytokine receptors, so that it acts as
      the major transducer of disparate cell functions, including changes in
      proliferation rate, cellular shape, attachment and motility, and regulation of
      proinflammatory activation. However, numerous experimental observations indicate
      that the different EGFR ligands are not redundant, but may rather provide
      distinct and specific contributions to keratinocyte functions. Importantly,
      increasing evidence now suggests that the EGFR pathway has a major impact on the
      inflammatory/immune reactions of the skin, in the apparent effort of enhancing
      innate immune defense while opposing overactivation of keratinocyte pro
      inflammatory functions. This review covers the molecular mechanisms and functions
      activated by this major growth factor system in the regulation of keratinocyte
      biology and focuses on the complex contribution of EGFR signaling to the
      inflammatory processes in the skin.

PMID- 18049452
TI  - Development of atopic dermatitis in mice transgenic for human apolipoprotein C1.
AB  - Mice with transgenic expression of human apolipoprotein C1 (APOC1) in liver and
      skin have strongly increased serum levels of cholesterol, triglycerides, and free
      fatty acids, indicative of a disturbed lipid metabolism. Importantly, these mice
      display a disturbed skin barrier function, evident from increased transepidermal
      water loss, and spontaneously develop symptoms of dermatitis including scaling,
      lichenification, excoriations, and pruritus. Histological analysis shows
      increased epidermal thickening and spongiosis in conjunction with elevated
      numbers of inflammatory cells (eosinophils, neutrophils, mast cells, macrophages,
      and CD4+ T cells) in the dermis. In addition, affected mice have increased serum
      levels of IgE and show abundant IgE(+) mast cells in the dermis. Partial
      inhibition of disease could be achieved by restoration of the skin barrier
      function with topical application of a lipophilic ointment. Furthermore, the
      development of atopic dermatitis in these mice was suppressed by corticosteroid
      treatment. These findings in APOC1(+/+) mice underscore the role of skin barrier
      integrity in the pathogenesis of atopic dermatitis.

PMID- 18049453
TI  - Pseudoxanthoma elasticum: oxidative stress and antioxidant diet in a mouse model
      (Abcc6-/-).
AB  - Pseudoxanthoma elasticum (PXE), a multisystem disorder characterized by ectopic
      mineralization of soft connective tissues, is caused by mutations in the ABCC6
      gene. The pathomechanistic details of the mineralization process are largely
      unknown, but oxidative stress has been suggested to play a role. In this study,
      we tested Abcc6(-/-) mice, which serve as a model of PXE, for markers of the
      oxidative stress in the liver and serum. The total antioxidant capacity as well
      as markers of protein oxidation and lipid peroxidation suggested the presence of
      chronic oxidative stress. Feeding these mice for 5 months with a diet
      supplemented with antioxidants (vitamins C and E, selenium, and N-acetylcysteine)
      countered the oxidative stress but did not modify the ectopic mineralization
      process. These results suggest that the Abcc6(-/-) mice suffer from chronic
      oxidative stress but this does not contribute to connective tissue
      mineralization, the hallmark of PXE.

PMID- 18049454
TI  - Glove-derived foreign proteins induce allergen-specific IgE in a mouse model.
AB  - Currently, most medical gloves are produced with a low content of natural rubber
      latex (NRL) protein. However, they may be substituted by proteins of foreign
      origin to maintain specific properties of the material. The aim of this study was
      to investigate the allergenicity and immunogenicity of unexpected proteins (i.e.,
      soy and casein) compared with NRL proteins in a murine model in BALB/c mice. All
      respective allergen sources (extracts from three brands of NRL gloves, soy, and
      casein) were able to induce significant allergen-specific IgE and IgG(1)
      responses. On average, the highest IgE induction occurred after immunization with
      NRL, followed by soy and casein. Certain individuals from each treatment group
      exhibited levels of specific IgE as high as due to NRL. To analyze further
      specific IgE responses on a single allergen level, we established a microarray
      based on recombinant allergens for allergen-specific murine IgE detection.
      Besides specific IgE against rHev b 3, -6, -7, -8, and -11, specific IgE against
      kappa-casein could be detected in mice immunized with NRL glove extract,
      indicating a sensitization potential of the contained foreign protein. The
      substitution of genuine latex proteins by proteins of foreign origin may lead to
      a shift and de novo increase in sensitization to the finished products.

PMID- 18049455
TI  - Coding and non-coding polymorphisms in alcohol dehydrogenase alters protein
      expression and alcohol-associated erythema.
AB  - Ethanol (EtOH), isopropyl alcohol (IPA), and propylene glycol (PG) increase
      topical drug delivery, but are sometimes associated with erythema. A potential
      genetic basis for alcohol-associated erythema was investigated as the function of
      polymorphisms in coding and non-coding regions of class IB alcohol dehydrogenase
      (ADHIB) and evaluated for altered gene expression in vitro and metabolic activity
      in vivo via altered skin blood flow (Doppler velocimeter) and erythema
      (reflectance colorimeter a*) following topical challenge to 5 M EtOH, IPA, PG,
      and butanol (ButOH). Promoter polymorphisms G-887A and C-739T and exon G143A form
      eight ADHIB haplotypes with different frequencies in Caucasians vs Asians and
      exhibit variable gene expression and metabolic activity. Polymorphisms C-739T and
      G-887A independently alter gene expression, which is further increased by IPA and
      PG, but not EtOH or ButOH. EtOH and ButOH increase erythema as a function of skin
      blood flow. IPA increases skin blood flow without erythema and PG increased
      erythema with decreased skin blood flow, all as a function of ADHIB haplotype. PG
      induced erythema was uniquely associated with tumor necrosis factor-alpha
      expression. Thus, erythema following alcohol exposure is alcohol type specific,
      has a pharmacogenetic basis related to ADHIB haplotype and can be functionally
      evaluated via Doppler velocimetry and reflectance colorimetry in vivo.

PMID- 18049456
TI  - A novel DSF-like signal from Burkholderia cenocepacia interferes with Candida
      albicans morphological transition.
AB  - In addition to producing lethal antibiotics, microorganisms may also use a new
      form of antagonistic mechanism in which signal molecules are exported to
      influence the gene expression and hence the ecological competence of their
      competitors. We report here the isolation and characterization of a novel
      signaling molecule, cis-2-dodecenoic acid (BDSF), from Burkholderia cenocepacia.
      BDSF is structurally similar to the diffusible signal factor (DSF) that is
      produced by the RpfF enzyme of Xanthomonas campestris. Deletion analysis
      demonstrated that Bcam0581, which encodes an RpfF homologue, was essential for
      BDSF production. The gene is highly conserved and widespread in the Burkholderia
      cepacia complex. Exogenous addition of BDSF restored the biofilm and
      extracellular polysaccharide production phenotypes of Xanthomonas campestris pv.
      campestris DSF-deficient mutants, highlighting its potential role in inter
      species signaling. Further analyses showed that Candida albicans germ tube
      formation was strongly inhibited by either coculture with B. cenocepacia or by
      exogenous addition of physiological relevant levels of BDSF, whereas deletion of
      Bcam0581 abrogated the inhibitory ability of the bacterial pathogen. As B.
      cenocepacia and C. albicans are frequently encountered human pathogens,
      identification of the BDSF signal and its activity thus provides a new insight
      into the molecular grounds of their antagonistic interactions whose importance to
      microbial ecology and pathogenesis is now becoming evident.

PMID- 18049457
TI  - Effect of earthworms on the community structure of active methanotrophic bacteria
      in a landfill cover soil.
AB  - In the United Kingdom, landfills are the primary anthropogenic source of methane
      emissions. Methanotrophic bacteria present in landfill biocovers can
      significantly reduce methane emissions via their capacity to oxidize up to 100%
      of the methane produced. Several biotic and abiotic parameters regulate methane
      oxidation in soil, such as oxygen, moisture, methane concentration and
      temperature. Earthworm-mediated bioturbation has been linked to an increase in
      methanotrophy in a landfill biocover soil (AC Singer et al., unpublished), but
      the mechanism of this trophic interaction remains unclear. The aims of this study
      were to determine the composition of the active methanotroph community and to
      investigate the interactions between earthworms and bacteria in this landfill
      biocover soil where the methane oxidation activity was significantly increased by
      the earthworms. Soil microcosms were incubated with 13C-CH4 and with or without
      earthworms. DNA and RNA were extracted to characterize the soil bacterial
      communities, with a particular emphasis on methanotroph populations, using
      phylogenetic (16S ribosomal RNA) and functional methane monooxygenase (pmoA and
      mmoX) gene probes, coupled with denaturing gradient-gel electrophoresis, clone
      libraries and pmoA microarray analyses. Stable isotope probing (SIP) using 13C
      CH4 substrate allowed us to link microbial function with identity of bacteria via
      selective recovery of 'heavy' 13C-labelled DNA or RNA and to assess the effect of
      earthworms on the active methanotroph populations. Both types I and II
      methanotrophs actively oxidized methane in the landfill soil studied. Results
      suggested that the earthworm-mediated increase in methane oxidation rate in the
      landfill soil was more likely to be due to the stimulation of bacterial growth or
      activity than to substantial shifts in the methanotroph community structure. A
      Bacteroidetes-related bacterium was identified only in the active bacterial
      community of earthworm-incubated soil but its capacity to actually oxidize
      methane has to be proven.

PMID- 18049458
TI  - Effects of aboveground grazing on coupling among nitrifier activity, abundance
      and community structure.
AB  - The influence of switches in grassland management to or from grazing on the
      dynamics of nitrifier activity, as well as the abundance of ammonia-oxidizing
      bacteria, AOB and ammonia-oxidizing archeae, AOA, was analyzed for two years
      after changing management. Additionally community structure of AOB was surveyed.
      Four treatments were compared in mesocosms: grazing on previously grazed
      grassland (G-G); no grazing on ungrazed grassland (U-U); grazing on ungrazed
      grassland (U-G) and cessation of grazing on grazed grassland (G-U). Nitrifier
      activity and abundance were always higher for G-G than U-U treatments and AOB
      community structure differed between these treatments. AOA abundance was in the
      same range as AOB abundance and followed the same trend. Grazing led to a change
      in AOB community structure within <5 months and a subsequent (5-12 months)
      increase in nitrifier activity and abundance. In contrast, cessation of grazing
      led to a decrease in nitrifier activity and abundance within <5 months and to a
      later (5-12 months) change in AOB community structure. Activity in G-U and U-G
      was similar to that in U-U and G-G, respectively, after 12 months. Sequence
      analysis of 16S rRNA gene clones showed that AOB retrieved from soils fell within
      the Nitrosospira lineage and percentages of AOB related to known Nitrosospira
      groups were affected by grazing. These results demonstrate that AOB and AOA
      respond quickly to changes in management. The selection of nitrifiers adapted to
      novel environmental conditions was a prerequisite for nitrification enhancement
      in U-G, whereas nitrification decrease in G-U was likely due to a partial
      starvation and decrease in the abundance of nitrifiers initially present. The
      results also suggest that taxonomic affiliation does not fully infer functional
      traits of AOB.

PMID- 18049459
TI  - Physiology and genetic traits of reverse osmosis membrane biofilms: a case study
      with Pseudomonas aeruginosa.
AB  - Biofilm formation of Pseudomonas aeruginosa on the surface of a reverse osmosis
      (RO) membrane was studied using a synthetic wastewater medium to simulate
      conditions relevant to reclamation of secondary wastewater effluent. P.
      aeruginosa biofilm physiology and spatial activity were analyzed following growth
      on the membrane using a short-life green fluorescent protein derivative expressed
      in a growth-dependent manner. As a consequence of the limiting carbon source
      prevailing in the suspended culture of the RO unit, a higher distribution of
      active cells was observed in the biofilm close to the membrane surface, likely
      due to the higher nutrient levels induced by concentration polarization effects.
      The faster growth of the RO-sessile cells compared to the planktonic cells in the
      RO unit was reflected by the transcriptome of the two cultures analyzed with DNA
      microarrays. In contrast to the findings recently reported in gene expression
      studies of P. aeruginosa biofilms, in the RO system, genes related to stress,
      adaptation, chemotaxis and resistance to antibacterial agents were induced in the
      planktonic cells. In agreement with the findings of previous P. aeruginosa
      biofilm studies, motility- and attachment-related genes were repressed in the RO
      P. aeruginosa biofilm. Supported by the microarray data, an increase in both
      motility and chemotaxis phenotypes was observed in the suspended cells. The
      increase in nutrient concentration in close proximity to the membrane is
      suggested to enhance biofouling by chemotaxis response of the suspended cells and
      their swimming toward the membrane surface.

PMID- 18049460
TI  - Comparison of lysogeny (prophage induction) in heterotrophic bacterial and
      Synechococcus populations in the Gulf of Mexico and Mississippi River plume.
AB  - Lysogeny has been documented as a fundamental process occurring in natural marine
      communities of heterotrophic and autotrophic bacteria. Prophage induction has
      been observed to be prevalent during conditions of low host abundance, but
      factors controlling the process are poorly understood. A research cruise was
      undertaken to the Gulf of Mexico during July 2005 to explore environmental
      factors associated with lysogeny. Ambient physical and microbial parameters were
      measured and prophage induction experiments were performed in contrasting
      oligotrophic Gulf and eutrophic Mississippi plume areas. Three of 11 prophage
      induction experiments in heterotrophic bacteria (27%) demonstrated significant
      induction in response to Mitomycin C. In contrast, there was significant
      Synechococcus cyanophage induction in seven of nine experiments (77.8%). A strong
      negative correlation was observed between lysogeny and log-transformed activity
      measurements for both heterotrophic and autotrophic populations (r=-0.876,
      P=0.002 and r=-0.815, P=0.025, respectively), indicating that bacterioplankton
      with low host growth favor lysogeny. Multivariate statistical analyses indicated
      that ambient level of viral abundance and productivity were inversely related to
      heterotrophic prophage induction and both factors combined were most predictive
      of lysogeny (rho=0.899, P=0.001). For Synechococcus, low ambient cyanophage
      abundance was most predictive of lysogeny (rho=0.862, P=0.005). Abundance and
      productivity of heterotrophic bacteria was strongly inversely correlated with
      salinity, while Synechococcus was not. This indicated that heterotrophic
      bacterial populations were well adapted to the river plume environments, thus
      providing a possible explanation for differences in prevalence of lysogeny
      observed between the two populations.

PMID- 18049461
TI  - Interactions between bacterial carbon monoxide and hydrogen consumption and plant
      development on recent volcanic deposits.
AB  - Patterns of microbial colonization and interactions between microbial processes
      and vascular plants on volcanic deposits have received little attention. Previous
      reports have shown that atmospheric CO and hydrogen contribute significantly to
      microbial metabolism on Kilauea volcano (Hawaii) deposits with varied ages and
      successional development. Relationships between CO oxidation and plant
      communities were not clear, however, since deposit age and vegetation status
      covaried. To determine plant-microbe interactions in deposits of uniform ages, CO
      and hydrogen dynamics have been assayed for unvegetated tephra on a 1959 deposit
      at Pu'u Puai (PP-bare), at the edge of tree 'islands' within the PP deposit (PP
      edge) and within PP tree islands (PP-canopy). Similar assays have been conducted
      for vegetated and unvegetated sites on a 1969 Mauna Ulu (MU) lava flow. Net in
      situ atmospheric CO uptake was highest at PP-edge and PP-bare sites (2.2+/-0.5
      and 1.3+/-0.1 mg CO m(-2) day(-1), respectively), and least for PP-canopy (-3.2+/
      0.9 mg CO m(-2) day(-1), net emission). Respiration rates, microbial biomass and
      maximum CO uptake potential showed an opposing pattern. Comparisons of
      atmospheric CO uptake and CO(2) production rates indicate that CO contributes
      significantly to microbial metabolism in PP-bare and MU-unvegetated sites, but
      negligibly where vegetation is well developed. Nonetheless, maximum potential CO
      uptake rates indicate that CO oxidizer populations increase with increasing plant
      biomass and consume CO actively. Some of these CO oxidizers may contribute to
      elevated nitrogen fixation rates (acetylene reduction) measured within tree
      islands, and thus, support plant successional development.

PMID- 18049464
TI  - Retraction: Reduced semen quality in chronic prostatitis patients that induce the
      release of apoptotic protein Omi/HtrA2 from spermatozoa.

PMID- 18049462
TI  - Report from London.

PMID- 18049465
TI  - Protein engineers turned evolutionists.
AB  - When generating novel tailor-made proteins, protein engineers routinely apply the
      principles of 'Darwinian' evolution. However, laboratory evolution of proteins
      also has the potential to test evolutionary theories and reproduce evolutionary
      scenarios, thus reconstructing putative protein intermediates and providing a
      glimpse of 'protein fossils'. This commentary describes research at the interface
      of applied and fundamental molecular evolution, and provides a personal view of
      how synergy between fundamental and applied experiments indicates novel and more
      efficient ways of generating new proteins in the laboratory.

PMID- 18049466
TI  - Dissecting protein structure and function using directed evolution.
AB  - To characterize the contributions of individual amino acids to the structure or
      function of a protein, researchers have adopted directed evolution approaches,
      which use iterated cycles of mutagenesis and selection or screening to search
      vast areas of sequence space for sets of mutations that provide insights into the
      protein of interest.

PMID- 18049467
TI  - Switching parasite proteins on and off.

PMID- 18049468
TI  - Illuminating aggregate heterogeneity in neurodegenerative disease.

PMID- 18049469
TI  - High-resolution insertion-site analysis by linear amplification-mediated PCR (LAM
      PCR).
AB  - Integrating vector systems used in clinical gene therapy have proven their
      therapeutic potential in the long-term correction of immunodeficiencies. The
      integration loci of such vectors in the cellular genome represent a molecular
      marker unique for each transduced cell and its clonal progeny. To gain insight
      into the physiology of gene-modified hematopoietic repopulation and vector
      related influences on clonal contributions, we have previously introduced a
      technology--linear amplification-mediated (LAM) PCR--for detecting and sequencing
      unknown DNA flanking sequences down to the single cell level (Supplementary Note
      online). LAM-PCR analyses have enabled qualitative and quantitative measurements
      of the clonal kinetics of hematopoietic regeneration in gene transfer studies,
      and uncovered the clonal derivation of non-leukemogenic and leukemogenic
      insertional side effects in preclinical and clinical gene therapy studies. The
      reliability and robustness of this method results from the initial
      preamplification of the vector-genome junctions preceding nontarget DNA removal
      via magnetic selection. Subsequent steps are carried out on a semisolid
      streptavidin phase, including synthesis of double complementary strands,
      restriction digest, ligation of a linker cassette onto the genomic end of the
      fragment and exponential PCR(s) with vector- and linker cassette-specific
      primers. LAM-PCR can be adjusted to all unknown DNA sequences adjacent to a known
      DNA sequence. Here we describe the use of LAM-PCR analyses to identify 5' long
      terminal repeat (LTR) retroviral vector adjacent genomic sequences.

PMID- 18049471
TI  - The war against influenza: discovery and development of sialidase inhibitors.
AB  - The threat of a major human influenza pandemic, in particular from highly
      aggressive strains such as avian H5N1, has emphasized the need for therapeutic
      strategies to combat these pathogens. At present, two inhibitors of sialidase
      (also known as neuraminidase), a viral enzyme that has a key role in the life
      cycle of influenza viruses, would be the mainstay of pharmacological strategies
      in the event of such a pandemic. This article provides a historical perspective
      on the discovery and development of these drugs--zanamivir and oseltamivir--and
      highlights the value of structure-based drug design in this process.

PMID- 18049472
TI  - Interferons at age 50: past, current and future impact on biomedicine.
AB  - The family of interferon (IFN) proteins has now more than reached the potential
      envisioned by early discovering virologists: IFNs are not only antivirals with a
      spectrum of clinical effectiveness against both RNA and DNA viruses, but are also
      the prototypic biological response modifiers for oncology, and show effectiveness
      in suppressing manifestations of multiple sclerosis. Studies of IFNs have
      resulted in fundamental insights into cellular signalling mechanisms, gene
      transcription and innate and acquired immunity. Further elucidation of the
      multitude of IFN-induced genes, as well as drug development strategies targeting
      IFN production via the activation of the Toll-like receptors (TLRs), will almost
      certainly lead to newer and more efficacious therapeutics. Our goal is to offer a
      molecular and clinical perspective that will enable IFNs or their TLR agonist
      inducers to reach their full clinical potential.

PMID- 18049473
TI  - The way forward in HCV treatment--finding the right path.
AB  - Infection with the hepatitis C virus (HCV) represents an important health-care
      problem worldwide. The prevalence of HCV-related disease is increasing, and no
      vaccine is yet available. Since the identification of HCV as the causative agent
      of non-A, non-B hepatitis, treatment has progressed rapidly, but morbidity and
      mortality rates are still predicted to rise. Novel, more efficacious and
      tolerable therapies are urgently needed, and a greater understanding of the viral
      life cycle has led to an increase in the number of possible targets for antiviral
      intervention. Here we review the specific challenges posed by HCV, and recent
      developments in the design of vaccines and novel antiviral agents.

PMID- 18049474
TI  - The design of drugs for HIV and HCV.
AB  - Since the discovery of the human immunodeficiency virus (HIV) in 1983, dramatic
      progress has been made in the development of novel antiviral drugs. The HIV
      epidemic fuelled the development of new antiviral drug classes, which are now
      combined to provide highly active antiretroviral therapies. The need for the
      treatment of hepatitis C virus (HCV), which was discovered in 1989, has also
      provided considerable impetus for the development of new classes of antiviral
      drugs, and future treatment strategies for chronic HCV might involve combination
      regimens that are analogous to those currently used for HIV. By considering the
      drug targets in the different stages of the life cycle of these two viruses, this
      article presents aspects of the history, medicinal chemistry and mechanisms of
      action of approved and investigational drugs for HIV and HCV, and highlights
      general lessons learned from anti-HIV-drug design that could be applied to HCV.

PMID- 18049475
TI  - Caenorhabditis elegans WNK-STE20 pathway regulates tube formation by modulating
      ClC channel activity.
AB  - WNK kinases are a small group of unique serine/threonine protein kinases that are
      conserved among multicellular organisms. Mutations in WNK1-4 cause
      pseudohypoaldosteronism type II-a form of hypertension. WNKs have been linked to
      the STE20 kinases and ion carriers, but the underlying molecular mechanisms by
      which WNKs regulate cellular processes in whole animals are unknown. The
      Caenorhabditis elegans WNK-like kinase WNK-1 interacts with and phosphorylates
      germinal centre kinase (GCK)-3--a STE20-like kinase--which is known to inactivate
      CLH-3, a CIC chloride channel. The wnk-1 or gck-3 deletion mutation causes an Exc
      phenotype, a defect in the tubular extension of excretory canals. Expression of
      the activated form of GCK-3 or the clh-3 deletion mutation can partly suppress
      wnk-1 or gck-3 defects, respectively. These results indicate that WNK-1 controls
      the tubular formation of excretory canals by activating GCK-3, resulting in
      downregulation of CIC channel activity.

PMID- 18049476
TI  - Che-1 activates XIAP expression in response to DNA damage.
AB  - X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of
      apoptosis proteins family that selectively binds and inhibits caspase-3, -7 and 
      9. As such, XIAP is an extremely potent suppressor of apoptosis and an attractive
      target for cancer treatment. Che-1 is an antiapoptotic agent involved in the
      control of gene transcription and cell proliferation. Recently, we showed that
      the checkpoint kinases ATM/ATR and checkpoint kinase 2 physically and
      functionally interact with Che-1 and promote its phosphorylation and accumulation
      in response to DNA damage. These Che-1 modifications induce transcription of p53,
      and Che-1 depletion strongly sensitizes tumor cells to anticancer drugs. Here we
      show that Che-1 activates XIAP expression in response to DNA damage. This effect
      is mediated by Che-1 phosphorylation and requires NF-kappaB. Notably, we found
      that XIAP expression is necessary for antiapoptotic activity of Che-1 and that in
      vivo downregulation of Che-1 by small interference RNA strongly enhanced the
      cytotoxicity of anticancer drugs.

PMID- 18049477
TI  - Identification and expansion of the tumorigenic lung cancer stem cell population.
AB  - Lung carcinoma is often incurable and remains the leading cancer killer in both
      men and women. Recent evidence indicates that tumors contain a small population
      of cancer stem cells that are responsible for tumor maintenance and spreading.
      The identification of the tumorigenic population that sustains lung cancer may
      contribute significantly to the development of effective therapies. Here, we
      found that the tumorigenic cells in small cell and non-small cell lung cancer are
      a rare population of undifferentiated cells expressing CD133, an antigen present
      in the cell membrane of normal and cancer-primitive cells of the hematopoietic,
      neural, endothelial and epithelial lineages. Lung cancer CD133(+) cells were able
      to grow indefinitely as tumor spheres in serum-free medium containing epidermal
      growth factor and basic fibroblast growth factor. The injection of 10(4) lung
      cancer CD133(+) cells in immunocompromised mice readily generated tumor
      xenografts phenotypically identical to the original tumor. Upon differentiation,
      lung cancer CD133(+) cells acquired the specific lineage markers, while loosing
      the tumorigenic potential together with CD133 expression. Thus, lung cancer
      contains a rare population of CD133(+) cancer stem-like cells able to self-renew
      and generates an unlimited progeny of non-tumorigenic cells. Molecular and
      functional characterization of such a tumorigenic population may provide valuable
      information to be exploited in the clinical setting.

PMID- 18049478
TI  - Fold up or perish: unfolded protein response and chemotherapy.

PMID- 18049479
TI  - Rap1 is involved in the signal transduction of myelin-associated glycoprotein.
AB  - Myelin-associated glycoprotein (MAG) is a well-characterized axon growth
      inhibitor in the adult vertebrate nervous system. Several signals that play roles
      in inhibiting axon growth have been identified. Here, we report that soluble MAG
      induces activation of Rap1 in postnatal cerebellar granule neurons (CGNs) and
      dorsal root ganglion (DRG) neurons. The p75 receptor associates with activated
      Rap1 and is internalized in response to MAG. After MAG is applied to the distal
      axons of the sciatic nerves, the activated Rap1, internalized p75 receptor, and
      MAG are retrogradely trafficked via axons to the cell bodies of the DRG neurons.
      Rap1 activity is required for survival of the DRG neurons as well as CGNs when
      treated with MAG. The transport of the signaling complex containing the p75
      receptor and Rap1 may play a role in the effect of MAG.

PMID- 18049480
TI  - Notch1 activation reduces proliferation in the multipotent hematopoietic
      progenitor cell line FDCP-mix through a p53-dependent pathway but Notch1 effects
      on myeloid and erythroid differentiation are independent of p53.
AB  - Signaling mediated by activation of the transmembrane receptor Notch influences
      cell-fate decisions, differentiation, proliferation, and cell survival. Activated
      Notch reduces proliferation by altering cell-cycle kinetics and promotes
      differentiation in hematopoietic progenitor cells. Here, we investigated if the
      G(1) arrest and differentiation induced by activated mNotch1 are dependent on
      tumor suppressor p53, a critical mediator of cellular growth arrest. Multipotent
      wild-type p53-expressing (p53(wt)) and p53-deficient (p53(null)) hematopoietic
      progenitor cell lines (FDCP-mix) carrying an inducible mNotch1 system were used
      to investigate the effects of proliferation and differentiation upon mNotch1
      signaling. While activated Notch reduced proliferation of p53(wt)-cells, no
      change was observed in p53(null)-cells. Activated Notch upregulated the p53
      target p21(cip/waf) in p53(wt)-cells, but not in p53(null)-cells. Induction of
      the p21(cip/waf) gene by activated Notch was mediated by increased binding of p53
      to p53-binding sites in the p21(cip/waf) promoter and was independent of the
      canonical RBP-J binding site. Re-expression of p53(wt) in p53(null) cells
      restored the inhibition of proliferation by activated Notch. Thus, activated
      Notch inhibits proliferation of multipotent hematopoietic progenitor cells via a
      p53-dependent pathway. In contrast, myeloid and erythroid differentiation was
      similarly induced in p53(wt) and p53(null) cells. These data suggest that Notch
      signaling triggers two distinct pathways, a p53-dependent one leading to a block
      in proliferation and a p53-independent one promoting differentiation.

PMID- 18049481
TI  - A molecular chaperone inducer protects neurons from ER stress.
AB  - The endoplasmic reticulum (ER) stress response is a defense system for dealing
      with the accumulation of unfolded proteins in the ER lumen. Recent reports have
      shown that ER stress is involved in the pathology of some neurodegenerative
      diseases and cerebral ischemia. In a screen for compounds that induce the ER
      mediated chaperone BiP (immunoglobulin heavy-chain binding protein)/GRP78 (78 kDa
      glucose-regulated protein), we identified BiP inducer X (BIX). BIX preferentially
      induced BiP with slight inductions of GRP94 (94 kDa glucose-regulated protein),
      calreticulin, and C/EBP homologous protein. The induction of BiP mRNA by BIX was
      mediated by activation of ER stress response elements upstream of the BiP gene,
      through the ATF6 (activating transcription factor 6) pathway. Pretreatment of
      neuroblastoma cells with BIX reduced cell death induced by ER stress.
      Intracerebroventricular pretreatment with BIX reduced the area of infarction due
      to focal cerebral ischemia in mice. In the penumbra of BIX-treated mice, ER
      stress-induced apoptosis was suppressed, leading to a reduction in the number of
      apoptotic cells. Considering these results together, it appears that BIX induces
      BiP to prevent neuronal death by ER stress, suggesting that it may be a potential
      therapeutic agent for cerebral diseases caused by ER stress.

PMID- 18049482
TI  - Firework-related eye injury in the UK.

PMID- 18049483
TI  - Retinoblastoma presenting as Coats' disease.

PMID- 18049484
TI  - The influence of the new general ophthalmic services (GOS) contract in
      optometrist referrals for glaucoma in Scotland.
AB  - PURPOSE: To assess the quality of referrals from community optometrists in the
      northeast of Scotland to the hospital glaucoma service before and after the
      implementation of the new General Ophthalmic Services (GOS) contract in Scotland.
      METHODS: Retrospective study encompassing two 6-month periods, one before the
      implementation of the new GOS (Scotland) contract in April 2006 (from June to
      November 2005), and the other after (from June to November 2006). The community
      optometrist referral forms and hospital glaucoma service notes were reviewed.
      Comparisons were performed using the t-test and chi (2)-test. RESULTS: In all,
      183 referrals were made during the first 6-month period from June to November
      2005, and 120 referrals were made during the second 6-month period from June to
      November 2006. After the introduction of the new GOS contract, there was a
      statistically significant increase in true-positive referrals (from 18.0 to
      31.7%; P=0.006), decrease in false-positive referrals (from 36.6 to 31.7%;
      P=0.006), and increase in the number of referrals with information on applanation
      tonometry (from 11.8 to 50.0%; P=0.000), dilated fundal examination (from 2.2 to
      24.2%; P=0.000), and repeat visual fields (from 14.8 to 28.3%; P=0.004) when
      compared to the first 6-month period. However, only 41.7% of referrals fulfilled
      the new GOS contract requirements, with information on applanation tonometry the
      most commonly missing. CONCLUSIONS: After the implementation of the new GOS
      (Scotland) contract in April 2006, there has been an improvement in the quality
      of the glaucoma referrals from the community optometrists in the northeast of
      Scotland, with a corresponding reduction in false-positive referrals. Despite the
      relatively positive effect so far, there is still scope for further improvement.

PMID- 18049485
TI  - Bilateral basal cell carcinoma of the lower eyelids following radium treatment
      for blepharitis.

PMID- 18049486
TI  - Amfenac increases the radiosensitivity of uveal melanoma cell lines.
AB  - PURPOSE: To evaluate the proliferation rates of five human uveal melanoma (UM)
      cell lines after treatment with amfenac, a cyclooxygenase (COX)-2 inhibitor, and
      subsequent radiation exposure. METHODS: Five human UM cell lines (92.1, SP6.5,
      MKT-BR, OCM-1, and UW-1) and one human fibroblast cell line (BJ) were incubated
      with amfenac. Treated and non-treated cell lines were then exposed to various
      doses of gammaradiation: 0, 2, 4, 6, and 8 Gy. Sulphorhodamine-B assay was used
      to assess proliferation rates 48 h post-radiation. RESULTS: Treatment of UM cell
      lines with amfenac prior to radiation led to a marked reduction in proliferation
      rates. This difference was statistically significant in all cell lines at every
      radiation dose (P<0.005), with the exception of 92.1 at 2 Gy (P=0.157).
      Fibroblasts treated with amfenac showed significantly higher proliferation rates
      after 2 and 8 Gy, with no significant differences at 0, 4, and 6 Gy. CONCLUSIONS:
      The radiosensitivity of UM cell lines was increased by the administration of
      amfenac, the active metabolite of nepafenac. There appears to be a
      radioprotective effect of amfenac on human fibroblasts. The topical
      administration of nepafenac may decrease tumour recurrence and radiation-induced
      complications while broadening the indications for radiotherapy by treating
      larger tumours.

PMID- 18049487
TI  - Papillophlebitis and uveitis as a manifestation of post-streptococcal uveitis
      syndrome.

PMID- 18049489
TI  - Efficacy of regulatory T-cell immunotherapy: are inflammatory cytokines key
      determinants?

PMID- 18049490
TI  - [CO2 + H2O = true].

PMID- 18049491
TI  - [Nobel Prize for genetic modification].

PMID- 18049492
TI  - [Multimodal treatment in colorectal cancer].

PMID- 18049493
TI  - [Food intolerance--a diagnostic challenge].

PMID- 18049494
TI  - [Evaluation of the genetic lactose intolerance test].
AB  - BACKGROUND: Lactose intolerance afflicts 5-10% of the population in western
      Europe, but is very common (up to 90%) in the southern hemisphere. Traditional
      analysis methods are based on lactose intake followed by determination of blood
      glucose concentration or exhaled H 2 and CH 4 . In many diagnostic laboratories,
      single nucleotide polymorphism (SNP) analysis on C/T-13910 has been introduced as
      a replacement for the traditional lactose intolerance testing. Homozygozity for
      the C-allele of this SNP results in very low or absent lactase enzyme activity.
      We have compared our present routine test (blood glucose measurements) to genetic
      SNP testing for C/T-13910. MATERIAL AND METHODS: Blood glucose measurements
      (after intake of lactose) and genotyping of C/T-13910 were performed on 137 adult
      participants after they had given informed consent. The maximal difference from
      fasting blood glucose was compared with real-time PCR analysis of C/T-13910.
      RESULTS AND INTERPRETATION: Lactose intolerance using blood glucose was positive
      for 20.4% of those tested; for the genetic test the corresponding result was
      17.5%. The correlation between the methods was strong (90%) with a kappa
      statistics index of 0.67 (0.51 - 0.83, 95% CI). Our results indicate that the
      genetic test for C/T-13910 complements the traditional phenotype measurements.

PMID- 18049495
TI  - [Borreliosis as the cause of disability pensions in Norway].
AB  - BACKGROUND: Borreliosis is a bacterial infection transferred by tick-bites.
      Neuroborreliosis is the most frequent disseminated form of the disorder in
      Norway. Registers exist in Norway on all reported communicable diseases (The
      Norwegian Surveillance System for Communicable Diseases [MSIS]) and disability
      pension diagnoses (The Norwegian Directorate of Labour and Welfare). MATERIAL AND
      METHODS: Geographic distributions of borreliosis and changes over time are
      presented. Disability pensions (coded by International Classification of Diseases
      [ICD]) in the period 1998-2005, in which borreliosis was used as the primary or
      secondary diagnosis (ICD-10), were compared with MSIS-data for borreliosis on
      municipal and county levels. RESULTS: Borreliosis was the cause of disability
      pensions in 55 cases. The Vestfold and Agder counties had the highest number of
      cases. Larvik municipality had 9 cases, Arendal had four and Kristiansand had
      nine cases. The annual rates of new disability pensions caused by borreliosis
      were low but increasing in the period 1998-2005. The disability pension rates
      tended to reflect changes in the number of MSIS-reported cases, with pensions
      changing 1-2 years after MSIS-changes. Most MSIS-reported cases are in the Agder
      and Telemark counties. INTERPRETATION: Disability pension are rarely caused by
      borreliosis. The annual incidence of disability pensions seems to reflect the
      number of MSIS-reported cases of borreliosis. The Agder and Vestfold counties
      have the highest incidence.

PMID- 18049496
TI  - [Migraine--mechanisms and consequences for treatment].
AB  - BACKGROUND: Migraine is a common headache syndrome. The understanding of
      processes in the brain during a migraine attack has increased significantly
      during recent years. MATERIAL AND METHODS: The article is based on literature
      retrieved from PubMed, and on own knowledge of older and more recent migraine
      literature. RESULTS AND INTERPRETATION: Patients with migraine probably have
      increased cortical excitability. Attacks may be initiated by the
      neurophysiological phenomenon "cortical spreading depression". This may again
      lead to meningeal inflammation and irritation of pain-sensitive fibres in the
      trigeminal nerve. There is compelling evidence that an episodic dysfunction of
      the brain stem plays an important role, either as a primary generator of or a
      secondary contributor to, migraine attacks. Patients often report allodynia as an
      expression for central sensitization. Activity in pain-modulating mechanisms is
      disturbed, and serotonin agonists efficiently stop attacks. The tendency to have
      repetitive migraine attacks is probably due to a genetic predisposition.

PMID- 18049497
TI  - [Dialysis treatment of infants with end stage failure].
AB  - BACKGROUND: End stage renal failure in infants is rare, and was until recently
      regarded as untreatable. Advancements in dialysis techniques and other renal
      replacement therapy, have now made lifesaving treatment possible. MATERIAL AND
      METHODS: Three infants who developed end stage renal failure shortly after birth
      and were subsequently treated with long-term dialysis (as a bridge to
      transplantation) are presented and their results are compared with those from
      other dialysis centres. RESULTS AND INTERPRETATION: All three patients were
      successfully dialysed until transplantation, two with peritoneal dialysis and one
      with haemodialysis. Complications were rare and manageable. The results are in
      accordance with findings from previous studies. Long-term dialysis in infants
      with chronic renal failure should no longer be considered experimental and is now
      a real alternative until the child is big enough to have a transplantation.
      Treatment outcome is affected by co-morbidity. The treatment requires a
      multidisciplinary approach with specialists from many fields including
      paediatrics, paediatric surgery, nephrology, nutrition and dialysis. In addition
      it is essential to cooperate with the parents, as the treatment is demanding for
      the family as well as for the medical personnel.

PMID- 18049498
TI  - [Classification of drug-related problems].
AB  - BACKGROUND: Drug-related problems are prevalent and cause considerable patient
      morbidity and in some cases death, as well as increased health care expenditures.
      A classification system may contribute to identify such problems, and further to
      resolve and prevent them. MATERIAL AND METHODS: A draft classification was
      circulated to a panel of physicians and pharmacists and comments were requested.
      Consensus was achieved after two subsequent hearing rounds where the structure,
      content and relevance of the draft were discussed. By means of mini cases the
      classification was validated concerning various professionals' understanding and
      interpretation of the problem categories. RESULTS: The classification has a
      hierarchical structure with 6 main categories (drug choice, dosing, adverse
      reaction, interaction, wrong use and other) and 12 subcategories. The system is
      relevant for hospitals, general practices, nursing homes and pharmacies.
      Validation of the system revealed that a majority would assign identical
      categories to 9/10 cases. INTERPRETATION: We propose a validated Norwegian
      classification system for drug-related problems. The systems may facilitate
      better and more systematic documentation and communication on such problems.

PMID- 18049499
TI  - [Limbic encephalitis--a diagnostic challenge].
AB  - BACKGROUND: The etiology of limbic encephalitis (LE) is often autoimmune.
      Autoimmune LE is often paraneoplastic and should be suspected in patients with
      subacute confusional states. Subgroups of LE require different treatment, and the
      prognosis is variable; making the correct diagnosis is therefore essential for a
      good outcome. MATERIAL AND METHODS: The article is based on the authors' clinical
      experience with these patients and a review of recent literature retrieved from
      PubMed with the key words limbic encephalitis, limbic inflammation,
      paraneoplastic encephalitis, limbic and cancer, ion channel antibodies and viral
      encephalitis. Two case reports illustrate important clinical points. RESULTS AND
      INTERPRETATION: Patients with LE constitute a heterogenous group with
      neuropsychiatric features, seizures and amnesia as the main symptoms. An early
      diagnosis is essential to limit sequelae. Viral encephalitis and Wernicke
      Korsakoff Syndrome are important differential diagnoses. Presence of an
      onconeural antibody in serum is a specific tumour marker that should be used for
      screening all patients for malignancy. Not all cases of LE are paraneoplastic;
      ion channel antibodies can be an important marker for good response to
      immunosuppressive therapy in this group.

PMID- 18049500
TI  - [Treatment of gastroesophageal reflux disease].

PMID- 18049501
TI  - [Radiotherapy of rectal cancer].
AB  - BACKGROUND: Of the approximately 1,100 new cases of rectal cancer in Norway
      annually, many can be cured by surgery alone, but a large group of patients need
      supplemental treatment. We here present the national consensus for radiotherapy
      of rectal cancer. MATERIAL AND METHODS: This review is based on relevant
      publications up to April 2007, the authors' own research and clinical
      experiences, data from The Norwegian Colorectal Cancer Register and guidelines
      from The Norwegian Gastrointestinal Cancer Group. RESULTS AND INTERPRETATION: It
      is important to discuss these patients in multidisciplinary teams (surgeon,
      oncologist, radiologist and preferably pathologist). Indications for preoperative
      radiotherapy are T4-tumours, tumours independent of the T-stadium that threaten
      the mesorectal fascie (3 mm or less from the tumour) or a pathologic lymph node
      in mesorectum. The indication for postoperative radiotherapy is perioperative
      perforation of a tumour or a R1-resection, i.e. histologically verified
      circumferential resection margin less than 2 mm. The radiotherapy is given in 2
      Gy fractions over 25 days concomitant with chemotherapy.

PMID- 18049502
TI  - [Adjuvant chemotherapy for colon cancer].
AB  - BACKGROUND: Radical resection is the main treatment for adenocarcinoma of the
      colon. Adjuvant chemotherapy may reduce the recurrence rate of the disease. It is
      therefore important that those who may benefit from such therapy are offered the
      optimal regimens in due time. The background for adjuvant chemotherapy of colon
      cancer is presented. MATERIAL AND METHODS: The manuscript is based on a survey of
      randomized clinical trials (from 1990 to 2007) retrieved from PubMed, and on own
      clinical experience. RESULTS AND INTERPRETATION: Cure rates after curative
      resections of colon cancer (stage III) are improved by about 12% if patients are
      treated with adjuvant chemotherapy with oxaliplatin combined with 5-fluoruracil
      and folinat (or capecitabine) for 6 months. Certain subgroups of stage II (Dukes'
      stage B) are also likely to benefit from adjuvant chemotherapy.

PMID- 18049503
TI  - [Treatment of locally recurrent rectal cancer].
AB  - BACKGROUND: It has not been common practice to operate local recurrence after
      rectal cancer and the treatment has received little attention in the J Norw
      Medical Ass. MATERIAL AND METHODS: This overview is based on literature retrieved
      from PubMed and own experience during 16 years. RESULTS AND INTERPRETATIONS: Type
      of local recurrence and the treatment related to it are classified and described.
      Most recurrences will benefit from preoperative irradiation. The difficulties
      caused by the confusion of postoperative fibrosis and recurrent cancer with
      regard to diagnosis, operability, the demand for multivisceral resection and the
      operative technique are discussed. The operations will often require cooperation
      between rectal surgeons, urologists, orthopaedists as well as plastic surgeons
      and gynaecologists. Our hospital has one of the largest published series, most
      other materials are small (< 70 patients). The results vary considerably
      regarding both survival and re-recurrences. This may be caused by differences in
      patient selection, oncological treatment and surgical aggressiveness. The
      surgical radicality is the most important prognostic factor. After a microscopic
      radical resection (R0 resection) the survival is similar to that for resection of
      Dukes C-grade primary colorectal cancer. The prognosis can probably be improved
      by improving the preoperative chemoradiation. This treatment should only be
      offered in a few centres in Norway because of the specific requirements.

PMID- 18049504
TI  - [Recurrence of rectal cancer--treatment in Norwegian hospitals].
AB  - BACKGROUND: The aim of this study was to examine if Norwegian surgeons had a
      passive attitude to treatment of patients with local recurrence of rectal cancer
      after primary treatment and if attitudes to treatment differed between hospitals.
      MATERIAL AND METHODS: All 46 departments for gastrointestinal surgery in Norway
      answered a questionnaire detailing their policy for workup, referral and
      treatment of patients with pelvic recurrence after surgery for rectal cancer.
      RESULTS: All hospitals used MRI for evaluation of the pelvis. Most clinics
      initially considered the patients potentially curable. Many wished to refer the
      patients to hospitals with more competence. Most patients in Norway are treated
      in eight different departments. Most of the surgeons give preoperative
      chemoradiotherapy before surgical resection of the local recurrence.
      INTERPRETATION: There seems to be a reasonable consensus among Norwegian surgeons
      about treatment of recurrent rectal cancer. The doctors themselves have to a
      certain degree centralized the treatment. Patients with recurrent rectal cancer
      should be discussed in multidisciplinary teams.

PMID- 18049505
TI  - [Fewer new drugs from drug industry].

PMID- 18049506
TI  - [Knowledge-based assessment of health risk].

PMID- 18049507
TI  - [Good choice of action, medical students!].

PMID- 18049508
TI  - [Women and blood pressure--an non-prioritized field].

PMID- 18049510
TI  - [Not only nirvana].

PMID- 18049512
TI  - Spatial interference of coherent atomic waves by manipulation of the internal
      quantum state.
AB  - A trapped >(87)Rb Bose-Einstein condensate is initially put into a superposition
      of two internal states. Under the effect of gravity and by means of a second
      transition, we prepare two vertically displaced condensates in the same internal
      state. These constitute two coherent sources of matter waves with adjustable
      spatial separation. Fringe patterns, observed after free expansion, are
      associated with the interplay between internal and external degrees of freedom
      and substantially agree with those for a double-slit experiment.

PMID- 18049513
TI  - Tapered holey fibers for spot-size and numerical-aperture conversion.
AB  - Adiabatically tapered holey fibers are shown to be potentially useful for guided
      wave spot-size and numerical-aperture conversion. Conditions for adiabaticity and
      design guidelines are provided in terms of the effective-index model. We also
      present finite-difference time-domain calculations of downtapered holey fiber,
      showing that large spot-size conversion factors are obtainable with minimal loss
      by use of short, optimally shaped tapers.

PMID- 18049514
TI  - Comparative study of large-mode holey and conventional fibers.
AB  - Little information exists regarding how large-mode holey fibers compare, in
      practical terms, with their conventional counterparts. We present what is to our
      knowledge the first experimental study of mode area and bend loss for a range of
      large-mode holey and conventional fibers. It is demonstrated here that large-mode
      holey fibers exhibit mode areas and bending losses that are comparable to those
      of conventional fibers at 1.55mu . However, the novel wavelength dependence of
      the numerical aperture in a holey fiber offers a significant advantage for
      broadband and short-wavelength applications in which single-mode operation is
      required.

PMID- 18049515
TI  - Four-wave mixing in microstructure fiber.
AB  - We report what we believe to be the first experimental demonstration of
      nondegenerate four-wave mixing in a microstructure fiber. The effect of the
      chi((3)) nonlinearity is enhanced in such a fiber because of the small core area,
      and we achieve phase matching by operating near the zero-dispersion wavelength
      (?750 nm) . We have observed parametric gains of more than 13 dB in 6.1-m-long
      fiber with a pump peak power of only 6 W. We compare our experimental gain
      results with those predicted by theory and explore the effects of Raman shift and
      (or) amplification and cascaded nonlinear mixing.

PMID- 18049516
TI  - Whispering-gallery-mode laser at 1.56 mum excited by a fiber taper.
AB  - We report the observation of whispering-gallery-mode lasers based on Er(3+) 
      doped ZBLAN microspheres coupled with half-tapered and tapered optical fibers. A
      multimode lasing effect is observed at 1.56mu when the taper diameters are
      properly adjusted so that their fundamental propagation constants match those of
      the resonant modes of interest. Overlap between the pump and the laser
      geometrical modes is optimized by pumping at 1.48mu .

PMID- 18049517
TI  - All-fiber tunable ytterbium-doped double-clad fiber ring laser.
AB  - We have designed and realized a cw all-fiber tunable Yb-doped double-clad fiber
      laser in a unidirectional ring cavity. The side-pumping V-groove technique is
      used, yielding very good launching efficiency of the high-power pumping laser
      diode, together with a compact configuration. The fiber laser delivers as much as
      800 mW of power and is tunable in the spectral range 1.04-1.10 microm . The laser
      linewidth is ~0.1 nm .

PMID- 18049518
TI  - Eye-safe actively Q-switched microchip laser with an electro-absorbing
      semiconductor modulator.
AB  - We present what we believe to be the first actively Q -switched monolithic
      microchip laser with a wavelength of 1.55 microm that uses an electro-absorbing
      semiconductor modulator. At an absorbed pump power of 130 mW and a switching
      voltage of 2.2 V, the laser produces 470-nJ pulses at a repetition rate of 10
      kHz. The output is a stable single longitudinal mode with a center wavelength of
      1.553 microm, and the transverse beam profile is close to an ideal Gaussian, with
      an M(2) value of 1.15.

PMID- 18049519
TI  - Instability in a laser-diode-pumped microchip Nd:YAG laser in a n-ary product
      scheme.
AB  - Dynamical instability, chaotic pulsations, and generalized bistability have been
      observed in a laser-diode-pumped microchip Nd:YAG laser operating in a double
      transition scheme in which lasing occurs on two transitions with overlapping gain
      profiles, F(3/2)(4)(2)? I(11/2)(4)(3) and F(3/2)(4)(1)? I(11/2)(4)(2), and
      simultaneously involves excited Nd atoms from different sublevels of the upper
      manifold. The modeling of the experimental results requires rate equations that
      include cross-gain coupling among oscillating modes that belong to different
      transitions whose population inversion densities are determined by the Boltzmann
      distribution.

PMID- 18049520
TI  - Optical scatter imaging: subcellular morphometry in situ with Fourier filtering.
AB  - We demonstrate a quantitative optical scatter imaging (OSI) technique, based on
      Fourier filtering, for detecting alterations in the size of particles with
      wavelength-scale dimensions. We generate our scatter image by taking the ratio of
      images collected at high and low numerical aperture in central dark-field
      microscopy. Such an image spatially encodes the ratio of wide to narrow angle
      scatter and hence provides a measure of local particle size. We validated OSI on
      sphere suspensions and live cells. In live cells, OSI revealed biochemically
      induced morphological changes that were not apparent in unprocessed differential
      interference contrast images. Unlike high-resolution imaging methods, OSI can
      provide size information for particles smaller than the camera's spatial
      resolution.

PMID- 18049521
TI  - Photon-transport forward model for imaging in turbid media.
AB  - A photon-transport forward model for image reconstruction in turbid media is
      derived that treats weak inhomogeneities through a Born approximation of the
      Boltzmann radiative transfer equation. This model can conveniently replace the
      commonly used diffusion approximation in optical tomography. An analytical
      expression of the background Green's function is obtained from the cumulant
      solution of the Boltzmann equation. Our model provides the correct behavior of
      photon migration at early times and reduces at long times to the center-moved
      diffusion approximation. Numerical comparisons between this model and the
      standard and center-moved diffusion models are presented.

PMID- 18049522
TI  - Simplified method for polarization-sensitive optical coherence tomography.
AB  - We report a method for extracting the birefringence properties of biological
      samples with micrometer-scale resolution in three dimensions, using a new form of
      polarization-sensitive optical coherence tomography. The method measures net
      retardance, net fast axis, and total reflectivity as a function of depth into the
      sample. Polarization sensing is accomplished by illumination of the sample with
      at least three separate polarization states during consecutive acquisitions of
      the same pixel, A scan, or B scan. The method can be implemented by use of non
      polarization-maintaining fiber and a single detector. In a calibration test of
      the system, net retardance was measured with an average error of 7.5 degrees
      (standard deviation 2.2 degrees ) over the retardance range 0 degrees to 180
      degrees , and a fast axis with average error of 4.8 degrees over the range 0
      degrees to 180 degrees .

PMID- 18049523
TI  - Three-dimensional total internal reflection microscopy.
AB  - We investigate the inverse-scattering problem that arises in total internal
      reflection microscopy. An analytic solution to this problem within the weak
      scattering approximation is used to develop a novel form of three-dimensional
      microscopy with subwavelength resolution.

PMID- 18049524
TI  - Real-time full-color three-dimensional display with a micromirror array.
AB  - We designed, realized, and tested what is believed to be the first real-time,
      full-color, autostereoscopic three-dimensional (3-D) display with a micromirror
      array. Compared with the diffractive partial pixel architecture [Opt. Lett. 20,
      1418 (1995)], this approach has certain advantages:(1) Micromirrors are
      reflective and thus achromatic (panchromatic) and (2) a variety of displays can
      be used as the image source. We used backlit transparencies to test the system
      and then used an ordinary color CRT to show several computer-generated full-color
      3-D animations.

PMID- 18049525
TI  - Acousto-optic lens with very fast focus scanning.
AB  - We propose and experimentally demonstrate an acousto-optic cylindrical lens with
      a very fast (400-kHz) focal scanning. The lens is realized by use of two adjacent
      acousto-optic scanners with counterpropagating acoustic waves that have the same
      frequency modulation but a pi phase difference. This scheme completely suppresses
      the lateral scan but adds the linear chirp of the two waves and thus functions as
      a fast focal-scan lens. We also demonstrate the use of this scanning lens in a
      very fast confocal profilometer.

PMID- 18049526
TI  - Dendrimer molecules with record large two-photon absorption cross section.
AB  - We report what is to our knowledge a record high value for an intrinsic two
      photon absorption (TPA) cross section, sigma(2) = 11 x 10(-47)> cm>(4)> s photon(
      1) molecule(-1), measured with femtosecond pulses in a new dendrimer molecule
      comprising 29 repeat units of 4, 4(?)-bis(diphenylamino)stilbene chromophore. We
      measure the dependence of TPA on excitation wavelength in three consecutive
      generations of the dendrimer and show that the maximum sigma(2) value increases
      faster than the total number of stilbene chromophores. This result indicates that
      it is possible to obtain even larger sigma(2) values in higher generations of
      this dendrimer family.

PMID- 18049527
TI  - Spatial patterns induced in a laser beam by thermal nonlinearities.
AB  - Stable spatial laser patterns were observed in a high-finesse Fabry-Perot cavity
      containing up to 2 atm of CO(2) and O(2). The gases displayed the same sequence
      of patterns that obey a scaling law of the form P(beta)p(2), where P is the power
      stored in the cavity, p is the pressure of the gas, and beta is a material
      dependent parameter.

PMID- 18049528
TI  - Wide-bandwidth 25-dB amplitude noise suppression in a pump-and-signal-resonant
      optical parametric oscillator.
AB  - We present a pump-and-signal-resonant optical parametric oscillator that provides
      25 dB of amplitude noise suppression of the transmitted pump beam from dc to 20
      kHz. The upper frequency range of the optical limiter increases as the pump power
      is increased, up to 1 MHz with 580 mW of input power. The amount of noise
      suppression is limited by pump-depletion effects. The upper frequency range is
      limited by the temporal response of the device. We present a numerical analysis
      that predicts this behavior.

PMID- 18049529
TI  - Temporal solitary waves due to optical rectification and the electro-optic
      effect.
AB  - Temporal solitary waves that are due to the mutual interaction of optical
      rectification and the electro-optic effect in the presence of a second-order
      nonlinearity are studied. It is found that a two-parameter family of solitons
      exists. Analytical solutions are found for special cases. Numerical soliton
      solutions of the system of equations include single- and multiple-hump solitary
      waves.

PMID- 18049530
TI  - Dark and bright photovoltaic spatial solitons in photorefractive crystals with
      positive refractive-index perturbation.
AB  - We have demonstrated, for what is believed to be the first time, that in a
      photorefractive crystal with positive refractive-index perturbation a two
      dimensional dark or bright photovoltaic spatial soliton can be formed in the same
      crystal by a signal beam and a background beam of different wavelengths. We
      discuss the conditions on the effective Glass constants and the absorption
      coefficients of the background and signal beams in determining the formation of
      the spatial soliton.

PMID- 18049531
TI  - Retardation-induced plasmon resonances in coupled nanoparticles.
AB  - We study the coupling induced by retardation effects when two plasmon-resonant
      nanoparticles are interacting. This coupling leads to an additional resonance,
      the strength of which depends on a subtle balance between particle separation and
      size. The scattering cross section and the near field associated with this
      coupled resonance are studied for cylindrical particles in air and in water.
      Implications for surface-enhanced Raman scattering and nano-optics are discussed.

PMID- 18049532
TI  - Sequence influence of nonidentical InGaAsP quantum wells on broadband
      characteristics of semiconductor optical amplifiers--superluminescent diodes.
AB  - Extremely broadband emission is obtained from semiconductor optical amplifiers
      superluminescent diodes with nonidentical quantum wells made of InGaAsP/InP
      materials. The well sequence is experimentally shown to have a significant
      influence on the emission spectra. With the three In(0.67) Ga(0.33) As(0.72)
      P(0.28) quantum wells near the n -cladding layer and the two In(0.53) Ga(0.47) As
      quantum wells near the p -cladding layer, all bounded by In(0.86) Ga(0.14)
      As(0.3)P(0.7) barriers, the emission spectrum could cover from less than 1.3 to
      nearly 1.55 microm, and the FWHM could be near 300 nm.

PMID- 18049533
TI  - Photonic crystal tapers for ultracompact mode conversion.
AB  - We have studied the coupling of a classic ridge waveguide with a two-dimensional
      photonic crystal (PC) waveguide, using finite-difference time-domain
      calculations. The ridge waveguide exhibits only a weak refractive-index
      confinement of light, as it is commonly used in buried-heterostructure or ridge
      waveguide lasers. The light is coupled to a PC waveguide that consists of one
      missing row along the ?K direction in a triangular lattice of air cylinders in
      AlGaAs. We compare various designs for PC tapers with that of a classic taper and
      for butt coupling. The calculation yields high coupling efficiency that exceeds
      80% for a 2.5-microm-long PC taper. In addition, the dependence of the efficiency
      on the PC air-fill factor and on alignment tolerances is analyzed.

PMID- 18049534
TI  - Direct detection of ultrafast thermal transients by use of a chirped,
      supercontinuum white-light pulse.
AB  - An experimental technique is demonstrated that permits direct optical measurement
      of ultrafast material transients during a single excitation-relaxation cycle.
      Reflection of a linearly chirped, supercontinuum optical pulse from a gold film
      with changing surface temperature induced by an ultrafast pump pulse allows the
      thermal transients to be encoded onto the spectrum of the probe pulse.
      Calibrating the chirp of the probe pulse and the wavelength sensitivity of the
      sample permits mapping of the measured transient into the time domain.
      Measurements are completed over the course of 100 ps with subpicosecond time
      resolution. Results obtained with this technique are compared with similar
      measurements obtained with conventional pump-probe correlation techniques.

PMID- 18049535
TI  - Exponentially convergent lattice sums.
AB  - For any oblique incidence and arbitrarily high order, lattice sums for one
      dimensional gratings can be expressed in terms of exponentially convergent
      series. The scattering Green's function can be efficiently evaluated also in the
      grating plane. Numerical implementation of the method is 200 times faster than
      for the previous best result.

PMID- 18049536
TI  - Phase quantization of a grating without altering the diffraction pattern.
AB  - Quantization of the phase-delay profile of a diffractive optical element often
      leads to unwanted deviations of considerable extent in the diffraction pattern. A
      method for avoiding this flaw for periodic phase gratings is described. The idea
      is to forgo strict periodicity and use the new degrees of freedom thus obtained
      to compensate for quantization-related deviations. The method is demonstrated for
      Fourier-array illuminator gratings designed with an iterative Fourier-transform
      algorithm.

PMID- 18049537
TI  - Study of spatial-temporal characteristics of optical fiber based on ultrashort
      pulse interferometry.
AB  - We demonstrate a method for reconstruction of the modal intensity distribution of
      light at the output of an optical fiber. Spatial modes of the optical fiber are
      separated in time as a result of differences in group velocity and are detected
      experimentally by observation of the interference of the modal field distribution
      with the time-gating reference field. The detected interference patterns of the
      modal fields are analyzed, providing the spatial impulse response of the fiber.
      We also use interferometric correlation to determine the spatiotemporal
      characteristics of the fiber modes, such as pulse width, linear chirp, and group
      velocity, for each mode.

PMID- 18049538
TI  - High-order dispersion-managed solitons for dense wavelength-division multiplexed
      transmissions.
AB  - Optimal dense wavelength-division multiplexed transmission is obtained based on
      high-order periodic dispersion-managed solitons in a dispersion-slope-compensated
      fiber link.

PMID- 18049539
TI  - Effects of precompensation and postcompensation on timing jitter in dispersion
      managed systems.
AB  - We present an analytic theory of timing jitter in dispersion-managed light-wave
      systems that is based on the moment method and the assumption of a chirped
      Gaussian pulse. We apply the theory to a soliton system and show that 50%
      postcompensation of the accumulated dispersion can reduce the jitter by a factor
      of 2. We also apply the theory to a low-power light-wave system employing the
      return-to-zero format and find that timing jitter can be minimized along the
      fiber link for an optimal choice of precompensation and postcompensation.

PMID- 18049540
TI  - Measurements of beat length in short low-birefringence fibers.
AB  - We describe a new experimental method of determining low birefringence in fibers,
      based on adjusting the fiber twist in a fiber-optic loop mirror. The method
      allows simple birefringence measurement in fibers with beat length within the
      range 0.05-100 m.

PMID- 18049541
TI  - Miniature all-fiber devices based on CO(2) laser microstructuring of tapered
      fibers.
AB  - A focused carbon dioxide laser beam is used to microstructure fibers that have
      already been narrowed by conventional fiber tapering. We describe three new
      miniature devices made with this technique: a fused fiber microcoupler with an
      interaction length of 200 mum, a long-period grating made from a periodic chain
      of microtapers, and a new type of prolate whispering-gallery mode microcavity.

PMID- 18049542
TI  - All-optical image processing by means of a photosensitive nonlinear liquid
      crystal film: edge enhancement and image addition-subtraction.
AB  - We demonstrate two simple yet efficient all-optical image-processing techniques
      that use nonlinear photosensitive dye-doped nematic liquid-crystal films, namely,
      edge enhancement and image addition-subtraction operations. These films require
      no external bias and function at much lower optical powers and shorter response
      times than other conventional methods.

PMID- 18049543
TI  - Demonstration of optical coherent transient true-time delay at 4 Gbits/s.
AB  - Multigigabit-per-second true time delay (TTD) was experimentally demonstrated by
      use of optical coherent transient techniques in a Tm(3+):YAG crystal. A delay
      accuracy of 1 ps and a delay resolution of 7 ps (both measurement limited) were
      achieved. The retrieved data retained good fidelity.

PMID- 18049544
TI  - Rainbow holographic camera.
AB  - A rainbow holographic camera system is presented. The system uses only a single
      laser beam for recording, so an antivibration arrangement is not required. The
      slit effect of the rainbow hologram is generated by replication from the slit
      master plate. Clear three-dimensional images have been sucessfully recorded by
      the system. The system is also useful for holographic interferometery.

PMID- 18049545
TI  - Simultaneous multicolor image formation with a single diffractive optical
      element.
AB  - A design for a novel diffractive optical element (DOE) that can reconstruct three
      different intensity patterns when it is illuminated by three different
      wavelengths is presented. If the chosen wavelengths are red, green, and blue,
      full-color reconstruction capability is obtained. Reconstruction is achieved in
      the near field (Fresnel domain). Computer simulation results as well as
      experimental evidence are presented, proving the capabilities of this novel DOE
      design procedure.

PMID- 18049546
TI  - Versatile 7-fs optical parametric pulse generation and compression by use of
      adaptive optics.
AB  - We have compressed the output from a beta-barium borate noncollinear optical
      parametric amplifier to ~7-fs pulse durations, using a micromachined deformable
      mirror with an efficient search algorithm. This compression method allows phase
      compensation of both material and gain dispersion, which produces an optimized
      wavelength-tunable pulse shape for ultrahigh-resolution time-domain spectroscopy.

PMID- 18049547
TI  - Pulse compression over a 170-THz bandwidth in the visible by use of only chirped
      mirrors.
AB  - We report on double-chirped mirrors with custom-tailored dispersion
      characteristics over a bandwidth of 170 THz in the visible. The mirrors are used
      in a prismless compressor for a noncollinear optical parametric amplifier in the
      visible. The compressed pulses, characterized for the what is believed to be
      first time by use of the spectral phase interferometry for direct electric field
      reconstruction technique, display a nearly flat phase from 510 to 710 nm and have
      a duration of 5.7 fs.

PMID- 18049548
TI  - Simultaneous generation of spectrally distinct third harmonics in a photonic
      crystal fiber.
AB  - By coupling femtosecond pulses at lambda - 1.55mum in a short length (Z - 95 cm)
      of photonic crystal fiber, we observe the simultaneous generation of two visible
      radiation components. Frequency-resolved optical gating experiments combined with
      analysis and modal simulations suggest that the mechanism for their generation is
      third-harmonic conversion of the fundamental pulse and its split Raman self
      shifted component.

PMID- 18049549
TI  - Three-dimensional object recognition by use of a photorefractive volume
      holographic processor.
AB  - We present a photorefractive volume holographic processor for recognition of
      three-dimensional (3D) objects. The templates are recorded by use of a volume
      hologram in a photorefractive LiNbO(3):Fe crystal located at the Fresnel
      diffraction region and correlated in real time with a 3D object illuminated by
      coherent light. Experimental results for recognition of 3D objects are presented
      and discussed. To the best of our knowledge, this is the first time a
      photorefractive volume holographic technique for 3D object recognition has been
      reported.

PMID- 18049550
TI  - Blind data restoration with an extracted filter function.
AB  - A method for performing blind deconvolutions on degraded images and data has been
      developed. The technique uses a power law relation applied to the Fourier
      transform of the degraded data to extract a filter function. This filter function
      closely resembles the point-spread function of the system and can be used to
      restore and enhance higher-frequency content. The process is noniterative and
      requires only that the point-spread function be space invariant and the transfer
      function be real. The algorithm has been validated by direct comparisons by use
      of a pseudoinverse filter with known transfer functions.

PMID- 18049551
TI  - Nulling interferometry by use of geometric phase.
AB  - Nulling interferometry is a method of detecting a faint source near a bright one,
      in which destructive interference is realized for the light from the bright
      source. A nulling interferometer that makes use of geometric phase (Pancharatnam
      phase) is proposed. An experimental setup is constructed to simulate a stellar
      interferometer with geometric-phase modulation. We attained extinction of 6 x 10(
      5) in white light.

PMID- 18049552
TI  - Displacement measurement with adjustable range by use of the photoelectromotive
      force effect and a frequency-modulated laser diode.
AB  - We demonstrate a scheme for displacement measurement by use of the
      photoelectromotive force effect and a frequency-modulated laser diode. The
      measurement range can be adjusted by a change in the depth of frequency
      modulation, thus making the measurement method both simple and versatile.

PMID- 18049553
TI  - All-optical programmable shaping of narrow-band nanosecond pulses with picosecond
      accuracy by use of adapted chirps and quadratic nonlinearities.
AB  - We experimentally demonstrate pure optical pulse picosecond shaping of narrow
      bandwidth nanosecond pulses. The method used is based on the manipulation in the
      spectral domain of strongly chirped femtosecond pulses and on the use of either
      frequency addition or frequency difference.

PMID- 18049554
TI  - Resonant excess quantum noise in focused-gain lasers.
AB  - We demonstrate that the transverse eigenmodes in a waveguide that combines a
      parabolic index guide with a Gaussian gain guide can be highly nonorthogonal. The
      excess-noise factor K that arises from this nonorthogonality exhibits resonant
      features with maximum values that can easily reach K approximately 400 . This
      simple model applies directly to stable-cavity microchip lasers with focused
      gain.

PMID- 18049555
TI  - Resonance Raman detection of carotenoid antioxidants in living human tissues.
AB  - We have used resonance Raman scattering as a novel noninvasive optical technology
      to measure carotenoid antioxidants in living human tissues of healthy volunteers.
      By use of blue-green laser excitation, clearly distinguishable carotenoid Raman
      spectra superimposed on a fluorescence background are obtained. The Raman spectra
      are obtained within less than a minute, and the required laser light exposure
      levels are well within safety standards. Our technique can be used for rapid
      screening of carotenoid levels in large populations and may have applications for
      assessing antioxidant status and the risk for diseases related to oxidative
      stress.

PMID- 18049556
TI  - Imaging of 1-nm-thick films with 193-nm microscopy.
AB  - We have implemented a reflected-light microscope operating in the deep
      ultraviolet at 193 nm. Many materials absorb strongly at this wavelength,
      providing greatly enhanced contrast compared with visible and near-ultraviolet
      microscopes. Polymer films as thin as 1 nm and SiO(2) films as thin as 3 nm have
      been imaged with this nonoptimized instrument. We have also calculated image
      contrast for several thin-film materials that are important in semiconductor
      processing, and we show that 193-nm light provides 60-485x better contrast than
      visible light (500 nm) and 4-95x better contrast than near-ultraviolet light (315
      nm) for these materials.

PMID- 18049557
TI  - Dipole-mode vector solitons in anisotropic nonlocal self-focusing media.
AB  - We demonstrate, theoretically and experimentally, that dipole-mode vector
      solitons created in biased photorefractive media possess a number of anisotropy
      driven properties, such as stability of a selected orientation, wobbling, and
      incomplete rotation, owing to the anisotropic nonlocal response of the
      photorefractive non-linearity. Such features are found for higher-order
      (multipole) vector solitons, and they are carefully verified in an experiment.

PMID- 18049558
TI  - Asymmetric transmissive behavior of liquid-crystal diffraction gratings.
AB  - We have used computer simulations to predict that the beam-steering efficiency of
      a common liquid-crystal diffraction grating will depend on which side is
      presented to the incident beam. The finite-difference time-domain method and the
      Helmholtz-Kirchhoff diffraction integral were utilized to simulate the
      performance of an idealized configuration of the grating.

PMID- 18049559
TI  - Mechanisms of ultrasonic modulation of multiply scattered coherent light: a Monte
      Carlo model.
AB  - A Monte Carlo model of the ultrasonic modulation of multiply scattered coherent
      light in scattering media is provided. The model is based on two mechanisms: the
      ultrasonic modulation of the index of refraction, which causes a modulation of
      the optical path lengths between consecutive scattering events, and the
      ultrasonic modulation of the displacements of scatterers, which causes a
      modulation of optical path lengths with each scattering event. Multiply scattered
      light accumulates modulated optical path lengths along its path. Consequently,
      the intensity of the speckles that are formed by the multiply scattered light is
      modulated. The contribution from the index of refraction is comparable with the
      contribution from displacement when the acoustic-wave vector is less than a
      critical fraction of the transport mean free path and becomes increasingly
      greater than the contribution from displacement beyond this critical point. This
      Monte Carlo model agrees well with an independent analytical model for
      isotropically scattering media. Both mechanisms are coherent phenomena, requiring
      the use of a coherent light source.

PMID- 18049560
TI  - Defective photonic crystals with greatly enhanced second-harmonic generation.
AB  - A one-dimensional defective photonic crystal structure is proposed with the aim
      of studying its nonlinear optical properties. In such a structure, extremely
      enhanced second-harmonic generation with an efficiency ~5 orders of magnitude
      higher than that of ordinary films is demonstrated in a numerical simulation.
      Extraordinary phase conditions of the process in such a structure were explored,
      and efficient forward and backward second-harmonic generation could be achieved
      simultaneously. The mechanism of the enhancement is the high field intensity and
      efficient wave coupling introduced by light localization in defect states, from
      which many other nonlinear processes can also benefit.

PMID- 18049561
TI  - Dielectric omnidirectional visible reflector.
AB  - We demonstrate the fabrication of an all-dielectric omnidirectional mirror for
      visible frequencies. The dielectric reflector consists of a stack of 19
      alternating layers of tin (IV) sulfide and silica. Using a combination of thermal
      evaporation (for tin sulfide) and thick electron-beam evaporation (for silica),
      we have achieved a refractive-index contrast of 2.6/1.46 , one of the highest
      refractive-index contrasts demonstrated in one-dimensional photonic bandgap
      systems designed for the visible frequency range. The tin sulfide-silica material
      system developed allowed the formation of a broadband visible reflector with an
      omnidirectional range greater than 10%. Possible applications of the system
      include efficient reflectors, high-frequency waveguides for communications and
      power delivery, and high- Q cavities.

PMID- 18049563
TI  - Fiber Fourier optics.
AB  - The Fourier transform of a coherent optical image can be evaluated physically by
      use of a single lens plus free-space propagation, thereby providing the basis for
      the field of Fourier optics. I point out that one can similarly evaluate the
      discrete Fourier transform of a sampled or pixelated optical array physically by
      passing the discrete array amplitudes through a network of single-mode fibers or
      optical waveguides. A passive optical network that evaluates the fast Fourier
      transform of a coherent array can be fabricated by use of (N/2)log(2)[N] optical
      3-dB couplers plus small added phase shifts. Implementing such networks in fiber
      or integrated optical form could provide the basis for a possible technology of
      fiber Fourier optics.

PMID- 18049562
TI  - Efficient high-order diffraction of extreme-ultraviolet light and soft x-rays by
      nanostructured volume gratings.
AB  - We report what is believed to be the first demonstration that volume gratings
      diffract extreme-ultraviolet light (EUV) or soft x-rays into high orders
      approximately an order of magnitude more efficiently than predicted by classical
      thin-grating theory. At the 13-nm wavelength, copolymer grating structures with
      200-nm period and aspect ratios of ~10:1 achieved diffraction efficiencies of
      11.2%, 15.3%, 11.5%, and 9.1% in the orders m of 2, 3, 4, and 5, respectively. In
      addition, the measured transmission spectra are consistent with electrodynamic
      calculations by coupled-wave theory. High-order diffraction can now be employed
      for substantially improved diffractive EUV and x-ray optics, e.g., highly
      resolving diffractive lenses and large-aperture condensers.

PMID- 18049564
TI  - Comment on "Rigorous solution for transient propagation of electromagnetic waves
      through a medium: causality plus diffraction in time".
AB  - In a previous Letter [Opt. Lett. 25, 995 (2000)], Xiao claimed to have found a
      "rigorous solution for transient propagation of electromagnetic waves through a
      medium." We show that Xiao's results apply strictly only to vacuum, which serves
      as a reference medium in classical electromagnetics.

PMID- 18049565
TI  - Nonlocal and spontaneous material responses: Reply to comment on "Rigorous
      solution for transient propagation of electromagnetic waves through a medium:
      causality plus diffraction in time".
AB  - I reply to the Comment by Weiglhofer and Lakhtakia on Opt. Lett. 25, 995 (2000).
      I agree with the comment to such an extent that it is generally known that
      nonlocal effects and material response time have to be considered in using
      collective macroscopic material response parameters. However, I believe that the
      Comment is incomplete and bears no special connection with the study that I
      reported in the original Letter.

PMID- 18049566
TI  - Simultaneous occurrence of beam deflection, holographic recording, and self
      interference in one lithium niobate crystal.
AB  - Coupling of the acousto-optic effect and the photorefractive effect in a
      magnesium-doped lithium niobate crystal was studied by a holographic recording
      technique. The process of self-interference that is due to the coupling of these
      two effects was observed. Our results demonstrate that beam splitting and
      deflection, holographic recording, and self-interference can occur simultaneously
      in one crystal.

PMID- 18049567
TI  - Fiber-optic liquid-level sensor using a long-period grating.
AB  - A liquid-level sensor based on the refractive-index sensitivity of long-period
      fiber-optic gratings is proposed and demonstrated. The form of the transmission
      spectrum of the long-period grating is dependent on the fraction of the length of
      the long-period grating that is surrounded by the liquid. The sensor shows a
      large linear range, with sensitivity of 4.8% change in transmission per
      millimeter, for a long-period grating with a length of 40 mm and a periodicity of
      400mu;m .

PMID- 18049568
TI  - Generation and dynamics of ghost pulses in strongly dispersion-managed fiber
      optic communication systems.
AB  - We investigate the nonlinear generation and dynamics of ghost pulses in high
      speed strongly dispersion-managed fiber-optic communication systems. Particular
      consideration is given to the importance of system parameters for the properties
      of the emerging ghost pulses. Conclusions are drawn about the growth rate and the
      temporal position of the ghost pulses in different systems.

PMID- 18049569
TI  - Low-temperature hypersensitization of phosphosilicate waveguides in hydrogen.
AB  - Conventional hydrogen loading of phosphosilicate optical fibers at relatively low
      temperatures (80 degrees C) is sufficient to enhance the fiber's photosensitivity
      after hydrogen outdiffusion, allowing permanent Bragg grating structures to be
      produced. Thermal sensitization is proposed to be a major contributor to stable
      index change.

PMID- 18049570
TI  - 2R-regenerative all-optical switch based on a highly nonlinear holey fiber.
AB  - We report the fabrication of a highly nonlinear holey fiber made from pure silica
      with an effective area of just ~2.8mu;m(2) at 1550 nm. We believe this to be the
      smallest effective area yet measured for a holey fiber at 1550 nm. We also report
      the operation of a 2R regenerative optical switch based on just 3.3 m of the
      fiber that is shown to have 30 times the nonlinear figure of merit of previous
      devices based on dispersion-shifted fiber.

PMID- 18049571
TI  - Control of critical coupling in a ring resonator-fiber configuration: application
      to wavelength-selective switching, modulation, amplification, and oscillation.
AB  - By controlling the internal loss of a ring resonator near critical coupling, we
      demonstrate control of the transmitted power in a fiber that is coupled to the
      resonator. We also demonstrate wavelength-selective optical amplification and
      oscillation.

PMID- 18049572
TI  - Bandpass filters based on pi-shifted long-period fiber gratings for actively mode
      locked erbium fiber lasers.
AB  - We have fabricated bandpass filters based on pi-shifted long-period gratings for
      application in actively mode-locked erbium fiber lasers. Introducing the pi-phase
      shift in the middle of the grating opens a bandpass within the core-cladding mode
      resonance peaks. With a 22-nm bandwidth filter inserted in an actively mode
      locked erbium fiber sigma laser, solitonlike pulses are generated, with a power
      dependent duration of approximately 3-5 ps , at a 3-GHz repetition rate. These
      all-fiber filters have the advantages of low insertion loss (<0.5 dB) and a wide
      bandwidth (10-20 nm), and they do not require that a circulator be inserted into
      the laser cavity.

PMID- 18049573
TI  - Optical image encryption with multistage and multichannel fractional Fourier
      domain filtering.
AB  - We present a novel image-encryption algorithm that employs multichannel and
      multistage fractional Fourier-domain filtering architecture. We perform the
      encryption and decryption by randomly filtering the spatial frequency of the
      image and then recombining the information from the algorithm in a multistage
      fractional Fourier domain with pure random-intensity-encoded masks and their
      complements in a multichannel scheme. The algorithm can be implemented
      iteratively in an electro-optical setup. Numerical simulations have verified the
      validity of the algorithm.

PMID- 18049574
TI  - Demonstration of a radio-frequency spectrum analyzer based on spectral hole
      burning.
AB  - Spectral hole-burning (SHB) technology is considered for >10-GHz instantaneous
      bandwidth signal-processing applications. In this context we report on what is
      believed to be the first demonstration of a SHB microwave spectrometer. A set of
      gratings engraved in a SHB crystal is used to filter one sideband of the
      optically carried microwave signal. The setup is confined to narrow-bandwidth
      operation, over a 35-MHz-wide interval. The first findings confirm the validity
      of the architecture in terms of spectral resolution, angular channel separation,
      and simultaneous detection of multiple spectral lines.

PMID- 18049575
TI  - Optical pattern recognition by use of a segmented semiconductor optical
      amplifier.
AB  - A technique for high-speed, all-optical pattern recognition based on cross
      correlation in a segmented semiconductor optical amplifier (SSOA) is presented. A
      counterpropagating pump-probe setup is used to perform cross correlation of the
      spatial gain-loss pattern in the SSOA with the optical data pattern (pump), and
      the result is read out with a counterpropagating probe. Cross correlation of 4
      bit patterns at 85 Gbits/s is experimentally demonstrated. Simulations show
      reasonable agreement with experimental measurements and are used to address
      scalability to higher bit rates and longer data patterns.

PMID- 18049576
TI  - Total reflection of light propagating from an isotropic medium to an anisotropic
      medium.
AB  - We study the propagation of light from an isotropic medium to an anisotropic
      medium. It is shown that total reflection can occur only for propagation from a
      denser medium to a rarer medium; this result does not agree with that of Lin and
      Wu [Opt. Lett. 23, 22 (1998)].

PMID- 18049577
TI  - High-pass filters give histograms with positive kurtosis.
AB  - If we filter an ensemble of natural images with a high-pass filter, the output is
      a random variable. The probability density for this variable will, under fairly
      general assumptions, be a Gaussian scale mixture. The kurtosis for this type of
      distribution is always positive.

PMID- 18049578
TI  - Technique for detecting changes in fluorescence lifetime by means of
      optoelectronic circuit auto-oscillation.
AB  - We present a new, simple, inexpensive, and highly precise approach to excited
      state fluorescence-lifetime-based measurements. The detection system consists of
      a closed-loop optoelectronic arrangement containing a radio frequency resonance
      amplifier, a fluorescence excitation light source, a fiber-optic delay line, and
      a photodetector. The system exhibits auto-oscillations in the form of intensity
      modulation. The oscillation frequency varies with the modulation phase shift of
      the fluorescent light. This frequency is used as the detection parameter, which
      is advantageous because frequency may be measured easily, inexpensively, and with
      high precision. This technique is well suited for chemical or biosensor
      applications.

PMID- 18049579
TI  - Quantitative measurement of low propagation losses at 1.55 mum on planar photonic
      crystal waveguides.
AB  - The Fabry-Perot resonance technique has been used to determine the propagation
      losses of planar photonic crystal (PC) waveguides. The structures are patterned
      into a GaInAsP confining layer on an InP substrate. Losses as low as 11 dB/mm
      have been measured on a guiding structure with three missing rows. The influence
      of the PC guide width and air-filling factor is demonstrated.

PMID- 18049581
TI  - Giant birefringence in anisotropically nanostructured silicon.
AB  - We performed a study of the in-plane birefringence of anisotropically
      nanostructured Si layers, which exhibit a greater difference in the main value of
      the anisotropic refractive index than that of natural birefringent crystals. The
      anisotropy parameters were found to be strongly dependent on the typical size of
      the Si nanowires used to assemble the layers. This finding opens the possibility
      of an application of birefringent Si retarders to a wide spectral range for
      control of the polarization state of light.

PMID- 18049580
TI  - 11-mJ, 15-Hz single-frequency diode-pumped Q-switched Er, Yb:phosphate glass
      laser.
AB  - A single-frequency diode-pumped Q-switched Er, Yb:phosphate glass laser that
      oscillates at an eye-safe 1.54etam wavelength has been developed for use in
      coherent Doppler lidar. A maximum TEM(00)-mode Q-switched output energy of 10.9
      mJ and a relatively long pulse width of 228 ns were obtained at a repetition rate
      of 15 Hz by use of a modified 2-m-long telescopic cavity. Frequency stability of
      as high as +/-1.9-MHz standard deviation and a side-mode suppression ratio of
      more than 30 dB were also achieved.

PMID- 18049582
TI  - Optical processing of light-induced autofluorescence for characterization of
      tissue pathology.
AB  - We describe an optical processing method for characterizing tissue pathology that
      is based on principal-component analysis of light-induced autofluorescence. A set
      of optical spectral filters, which are related to the principal-component loading
      vectors, is designed to process the autofluorescence signal optically and to
      generate principal-component scores from the autofluorescence spectra. The scores
      are then correlated with the tissue pathology. An optical processing system is
      designed that uses the in vivo fluorescence spectra recorded from nasopharyngeal
      tissues. We demonstrate that the system can differentiate nasopharyngeal
      carcinoma from normal tissue with a high degree of sensitivity and specificity
      and that the optical filters used in the system can be manufactured.

PMID- 18049583
TI  - Phase-referenced interferometer with subwavelength and subhertz sensitivity
      applied to the study of cell membrane dynamics.
AB  - We report a highly sensitive means of measuring cellular dynamics with a novel
      interferometer that can measure motional phase changes. The system is based on a
      modified Michelson interferometer with a composite laser beam of 1550-nm low
      coherence light and 775-nm CW light. The sample is prepared on a coverslip that
      is highly reflective at 775 nm. By referencing the heterodyne phase of the 1550
      nm light reflected from the sample to that of the 775-nm light reflected from the
      coverslip, small motions in the sample are detected, and motional artifacts from
      vibrations in the interferometer are completely eliminated. We demonstrate that
      the system is sensitive to motions as small as 3.6 nm and velocities as small as
      1 nm/s. Using the instrument, we study transient volume changes of a few
      (approximately three) cells in a monolayer immersed in weakly hypotonic and
      hypertonic solutions.

PMID- 18049584
TI  - Fixing multiple waveguides induced by photorefractive solitons: directional
      couplers and beam splitters.
AB  - We show how to transform multiple real-time photorefractive solitons into
      permanent two-dimensional single-mode waveguides impressed into the crystalline
      lattice of the host material. We experimentally demonstrate two specific
      configurations of such fixed multiple waveguides: directional couplers and
      multiple beam splitters.

PMID- 18049585
TI  - Efficiency of quadratic soliton generation.
AB  - We report what is believed to be the first experimental demonstration of soliton
      content as a function of the intensity of input light for multicolor quadratic
      solitons. Experiments were conducted with spatial solitons excited with Gaussian
      beams in a bulk crystal cut for second-harmonic generation. The effects
      introduced by the finite crystal length and by the scheme employed to elucidate
      the soliton energy are highlighted.

PMID- 18049586
TI  - Micromachined silicon nitride deformable mirrors for focus control.
AB  - We have built a 1000mum-diameter silicon nitride deformable mirror for focus
      control applications, using micro-optoelectromechanical systems technology. We
      achieved variable focal lengths from 36 to 360 mm while maintaining zero primary
      spherical aberration, using a maximum control voltage of 100 V. Active control of
      spherical aberration of approximately two waves at 660 nm was demonstrated.

PMID- 18049587
TI  - Optical-frequency balanced mixer.
AB  - Optical signal processing devices based on quasi-phase-matched three-wave mixing
      and cascaded three-wave mixing in guided-wave geometries have been demonstrated
      to operate efficiently at practical pump-power levels. We describe operation of
      such devices in a balanced mode that allows mixing without wavelength offset and
      separation of mixed output from pump and signal input without wavelength
      selective filters. We present a design for an optical-frequency balanced mixer
      using quasi-phase-matched, cascaded second-order nonlinear processes. Using this
      design, we fabricated a balanced mixer in periodically poled lithium niobate
      waveguides that has the expected linear and nonlinear optical performance.

PMID- 18049588
TI  - Influence of nanoscale cutoff in random self-affine fractal silver surfaces on
      the excitation of localized optical modes.
AB  - We report rigorous numerical calculations of the near field scattered from rough,
      one-dimensional self-affine fractal silver surfaces. We show that fractal lower
      scale cutoff (decreased to the order of tens of nanometers) has a strong effect
      on excitation and strength of localized optical modes, leading to very large
      enhancements of the intensity (larger than 10(4)) and fluctuations of the
      electric field.

PMID- 18049589
TI  - Evidence for particle-shape sensitivity in the correlation between polarization
      states of light scattering.
AB  - The cross correlation between polarization states of scattered laser speckle as a
      function of scattering angle is observed for a range of spherical and
      nonspherical particle suspensions. A variation in the degree of correlation
      between polarization states is observed, and this information is indicative of
      the particle shape. A comparison with a theoretical model for small particles is
      made, suggesting that variations in polarization correlation with angle originate
      from the nonisotropic polarizability of nonspheres. Experiments are also
      performed on large spheroids and random-shaped polydispersions, and the results
      indicate that the measurement method has significant potential for nonsphere
      detection and characterization.

PMID- 18049590
TI  - C-axis Josephson plasma resonance observed in Tl(2)Ba(2)CaCu(2)O(8)
      superconducting thin films by use of terahertz time-domain spectroscopy.
AB  - We have unambiguously observed the c -axis Josephson plasma resonance (JPR) in
      high-critical-temperature (T(c)) cuprate (Tl(2)Ba(2)CaCu(2)O(8)) superconducting
      thin films, employing terahertz time-domain spectroscopy in transmission as a
      function of temperature in zero magnetic field. These are believed to be the
      first measurements of the JPR temperature dependence of a high-T(c) material in
      transmission. With increasing temperature, the JPR shifts from 705 GHz at 10 K to
      ~170 GHz at 98 K, corresponding to an increase in c-axis penetration depth from
      22.4+/-0.6mum to 94+/-9mum . The linewidth of the JPR peak increases with
      temperature, which indicates an increase in the quasi-particle scattering rate.
      We have probed the onset of the c -axis phase coherence to ~0.95T(c) . The JPR
      vanishes above T(c) as expected.

PMID- 18049591
TI  - Carrier-phase control among subharmonic pulses in a femtosecond optical
      parametric oscillator.
AB  - We have generated femtosecond subharmonic pulses by using an optical parametric
      oscillator. The optical frequencies of the idler and the signal are one third and
      two thirds, respectively, of the optical frequency of the pump pulse. The carrier
      phase of the signal pulse relative to that of the pump pulse was locked by
      electronic feedback. The carrier-envelope phase slip frequency of the signal
      pulse relative to that of the pump was locked to F/6 , where F is defined as the
      repetition frequency.

PMID- 18049592
TI  - Observation of Ramsey fringes in an atomic cell with buffer gas.
AB  - Temporal Ramsey fringes that are due to light scattering by coherently prepared
      rubidium atoms diffusing through a cell containing neon as a buffer gas have been
      observed. The effect leads to increasing magneto-optical rotation of cw light
      polarization at weak magnetic fields.

PMID- 18049593
TI  - Wideband tunable wavelength conversion of 10-Gbit/s return-to-zero signals by
      optical time gating of a highly chirped rectangular supercontinuum light source.
AB  - We propose a novel technique for wideband tunable wavelength conversion of return
      to-zero signals by optical time gating of a supercontinuum (SC) light source. A
      SC pulse generated by nonlinear propagation in a normal-dispersion fiber has a
      rectangular shape with highly linear upchirping. By control of the optical time
      gating position, the center wavelength of time-gated SC pulse can be precisely
      tuned. Error-free 10-Gbit/s wavelength conversion with a tuning range of 27.1 nm
      is experimentally demonstrated.

PMID- 18049594
TI  - Figure of merit for near-velocity-matched traveling-wave modulators.
AB  - We derive a relationship between the bandwidth and active length and a figure of
      merit for velocity- and near-velocity-matched lithium niobate traveling-wave
      electro-optic modulators. The figure of merit is given by the bandwidth per unit
      drive voltage squared and is independent of the length of the device.
      Alternatively, this figure of merit can be described by its inverse, which is
      proportional to the device's switching energy.

PMID- 18049595
TI  - Fiber delivery of femtosecond pulses from a Ti:sapphire laser.
AB  - We propose a way to deliver nanojoule-energy, 100-fs pulses at 800 nm through a
      few meters of standard optical fiber. Pulses from a mode-locked laser are
      compressed temporally, and then spectrally, to produce the desired pulses at the
      end of the fiber. Initial experiments agree well with calculations and
      demonstrate the benefits of this technique: For an energy of ~0.5 nJ , the
      delivered pulses are ~5 times shorter than those delivered by other techniques.
      The issues that must be addressed to scale the technique up to delivered pulse
      energies of 5 nJ are identified, and the apparatus employs only readily available
      components. Thus we expect it to find use in the many applications that would
      benefit from fiber delivery of femtosecond pulses.

PMID- 18049596
TI  - Algebraic and geometric space-time analogies in nonlinear optical pulse
      propagation.
AB  - We extend recently developed algebraic space-time analogies for the dispersive
      and nonlinear propagation of optical breathers. Geometrical arguments can explain
      the similarity of evolutionary behavior between spatial and temporal phenomena
      even when strict algebraic translation of solutions may not be possible. This
      explanation offers a new set of tools for understanding and predicting the
      evolutionary structure of self-consistent Gaussian breathers in nonlinear optical
      fibers.

PMID- 18049597
TI  - Single-frequency master-oscillator fiber power amplifier system emitting 20 W of
      power.
AB  - We report a master-oscillator fiber power-amplifier system consisting of a diode
      pumped monolithic nonplanar ring laser as the master oscillator and a Yb-doped
      large-mode-area double-clad fiber as the power amplifier. The system emits up to
      20.1 W of single-frequency radiation at a wavelength of 1064 nm with diffraction
      limited beam quality (M(2)</=1.3) . The optical emission spectrum and amplitude
      noise behavior are investigated. Furthermore, the power-scaling possibilities are
      discussed.

PMID- 18049598
TI  - Optimized grating-frustrated coupler.
AB  - A complete theoretical analysis of a modified grating-frustrated coupler with a
      second grating in the input channel is presented. We show that this second
      grating allows for a reduction to zero of backreflected light and transmits all
      the radiation near the Bragg wavelength to a drop port.

PMID- 18049599
TI  - Broadband laser amplifier based on gas-phase dimer molecules pumped by the Sun.
AB  - We report the design and experimental realization of a solar-pumped dimer gas
      laser amplifier. The amplifying medium is Te(2) gas, which is capable of
      amplifying laser signals over a broad spectral range. A gain of 42% was measured
      at a wavelength of 632.8 nm. We also present studies of the material
      characteristics and a brief review of the study of other candidate materials for
      solar pumping.

PMID- 18049600
TI  - Perturbation Monte Carlo methods to solve inverse photon migration problems in
      heterogeneous tissues.
AB  - We introduce a novel and efficient method to provide solutions to inverse photon
      migration problems in heterogeneous turbid media. The method extracts derivative
      information from a single Monte Carlo simulation to permit the rapid
      determination of rates of change in the detected photon signal with respect to
      perturbations in background tissue optical properties. We then feed this
      derivative information to a nonlinear optimization algorithm to determine the
      optical properties of the tissue heterogeneity under examination. We demonstrate
      the use of this approach to solve rapidly a two-region inverse problem of photon
      migration in the transport regime, for which diffusion-approximation-based
      approaches are not applicable.

PMID- 18049602
TI  - Polarization coherent anti-Stokes Raman scattering microscopy.
AB  - We report polarization coherent anti-Stokes Raman scattering (P-CARS) microscopy
      that allows vibrational imaging with high sensitivity and spectral selectivity.
      The nonresonant background signals from both Raman scatterers and the solvent are
      efficiently suppressed in P-CARS microscopy. We demonstrate P-CARS imaging of
      unstained cells based on the contrast of the protein amide I band.

PMID- 18049601
TI  - Whole-field five-dimensional fluorescence microscopy combining lifetime and
      spectral resolution with optical sectioning.
AB  - We report a novel whole-field three-dimensional fluorescence lifetime imaging
      microscope that incoporates multispectral imaging to provide five-dimensional (5
      D) fluorescence microscopy. This instrument, which can acquire a 5-D data set in
      less than a minute, is based on potentially compact and inexpensive diode-pumped
      solid-state laser technology. We demonstrate that spectral discrimination as well
      as optical sectioning minimize artifacts in lifetime determination and illustrate
      how spectral discrimination improves the lifetime contrast of biological tissue.

PMID- 18049603
TI  - Transient dark photovoltaic spatial solitons and induced guiding in slab LiNbO(3)
      waveguides.
AB  - Dark photorefractive photovoltaic spatial solitons are demonstrated at 532 nm in
      nominally undoped and slightly Fe-doped LiNbO(3) planar optical waveguides. The
      spatial solitons are observed in a transient regime before transverse modulation
      instability occurs. Their widths are intensity independent as predicted by
      theory. Meanwhile, excited mode distribution and Fe-doping concentration are
      shown to influence soliton width. The guiding properties of soliton-induced
      waveguides are also presented.

PMID- 18049604
TI  - Second-harmonic generation in Ge(20)As(25)S(55) glass irradiated by an electron
      beam.
AB  - Second-harmonic generation was observed in Ge(20)As(25)S(55) chalcogenide glass
      irradiated by an electron beam. The second-harmonic intensity increased with
      increasing electron-beam current and accelerating voltage. The second-harmonic
      generation in Ge(20)As(25)S(55) glass was caused by the space-charge
      electrostatic field that was generated by irradiation of an electron beam. Second
      order nonlinearity X((2)) as great as 0.8 pm/V was obtained. The results of
      measurements of thermally stimulated depolarization current indicated that the
      glass was poled in the thin layers of its surface (several micrometers) and that
      the nonlinearity was stable.

PMID- 18049605
TI  - Generation of mid-infrared pulses by X(3) difference frequency generation in
      CaF(2) and BaF(2).
AB  - Tunable mid-IR pulses in the range 1300-4200 cm(-1) (7.7-2.4 microm) are
      generated through a phase-matched four-wave mixing process in ordinary mid-IR
      window materials such as CaF(2) and BaF(2) . In this process the difference
      frequency v(3)=2v(2)-v(1) is generated from pump fields v(1) and v(2) . The
      process can be phase matched to different frequencies by adjustment of the angle
      between the pump fields.

PMID- 18049606
TI  - Experimental demonstration of 1535-1555-nm simultaneous optical wavelength
      interchange with a nonlinear photonic crystal.
AB  - We present results of what is to our knowledge the first experimental
      demonstration of simultaneous optical wavelength interchange by use of a two
      dimensional second-order nonlinear photonic crystal. Fabrication and performance
      parameters of a 1535-1555-nm wavelength interchange nonlinear photonic crystal
      fabricated in lithium niobate are discussed.

PMID- 18049607
TI  - White-light supercontinuum generation with 60-ps pump pulses in a photonic
      crystal fiber.
AB  - The generation of a spatially single-mode white-light supercontinuum has been
      observed in a photonic crystal fiber pumped with 60-ps pulses of subkilowatt peak
      power. The spectral broadening is identified as being due to the combined action
      of stimulated Raman scattering and parametric four-wave-mixing generation, with a
      negligible contribution from the self-phase modulation of the pump pulses. The
      experimental results are in good agreement with detailed numerical simulations.
      These findings demonstrate that ultrafast femtosecond pulses are not needed for
      efficient supercontinuum generation in photonic crystal fibers.

PMID- 18049608
TI  - Three-dimensional magneto-optic trap for micro-object manipulation.
AB  - A magneto-optic trap for micro-objects is described. Magnetic beads were trapped
      by optical tweezers while being rotated by a new integrated magnetic manipulator.
      Rotation was achieved with eight electromagnets with tip-pole geometry. The time
      orbital potential technique was used to achieve rotation of magnetic beads.
      Trapping in three dimensions and rotation of magnetic beads on three axes are
      demonstrated with forces up to 230 pN and force momenta of up to 10(-16)N m . A
      position-detection apparatus based on an interferometric scheme provides
      nanometer sensitivities in a few milliseconds.

PMID- 18049609
TI  - Sensitivity-bandwidth product for electro-optic modulators.
AB  - For lumped-element electro-optic modulators, the sensitivity ( partial
      differentialphi/ partial differentialV) of the phase, phi , in response to an
      applied voltage V is related to the optical group delay, T(g) , and the
      bandwidth, Domega . This relationship imposes a fundamental trade-off between the
      sensitivity and the bandwidth of electro-optic modulators: ( partial
      differentialphi/ partial differentialV)Domega= (dn/dV)(omega /n) , where n is the
      optical index. A similar relationship for traveling-wave modulators sets an upper
      limit on ( partial differentialphi/ partial differentialV) that is proportional
      to T(g) .

PMID- 18049610
TI  - Diffraction-free and dispersion-free pulsed beam propagation in dispersive media.
AB  - The diffraction of pulsed beams of light is formulated as an anomalously
      dispersive phenomenon. In a dispersive material, the effects of material group
      velocity dispersion and diffraction on pulsed beam propagation can mutually
      cancel if the transverse profile of the pulse is suitably chosen.

PMID- 18049611
TI  - Generation of correlated photons in controlled spatial modes by downconversion in
      nonlinear waveguides.
AB  - We report the observation of correlated photon pairs generated by spontaneous
      parametric downconversion of a 400-nm pump pulse in a quasi-phase-matched
      KTiOPO(4) nonlinear waveguide. The highest ratio of coincidence to single-photon
      count rates observed near 800 nm exceeds 18%. This suggests that nonlinear
      waveguides will be a promising source of correlated photons for metrology and
      quantum information processing applications. We also discuss possibilities of
      controlling the spatial characteristics of the downconverted photons produced in
      multimode waveguide structures.

PMID- 18049612
TI  - Low-loss infrared dielectric material system for broadband dual-range
      omnidirectional reflectivity.
AB  - A material system for broadband thermal IR applications based on branched
      polyethylene and tellurium is introduced. This system exhibits low absorption
      losses from 3.5 to 35 microm , has a large index contrast, and is readily
      deposited as a thin film. These unique features were used to investigate the
      formation of an omnidirectional reflector that exhibits two distinct, broadband
      omnidirectional ranges at thermal wavelengths. Reflectivity measurements are
      presented that confirm the existence of two omnidirectional ranges in the solar
      atmospheric windows extending from 8 to 12 microm and from 4.5 to 5.5 microm .
      The measurements are in good agreement with simulations.

PMID- 18049613
TI  - Spatiotemporal control of ultrashort optical pulses by refractive-diffractive
      dispersive structured optical elements.
AB  - Structured optical elements that control the spatial and temporal characteristics
      of femtosecond light pulses are analyzed and synthesized. We show that unique
      spatiotemporal effects can be attained based on the diffraction, refraction, and
      dispersive effects that appear in the femtosecond regime. We argue that the
      design requirements for ultrafast optics are beyond the achromatization
      considerations that are usually applied to incoherent illumination because of the
      need to consider coherent effects. Despite fundamental limitations in the space
      time control of ultrashort pulses, we show the potential of this technique to
      improve simultaneously the spatial and the temporal resolution of a lens and to
      generate ultrafast pulse sequences.

PMID- 18049614
TI  - White-light frequency comb generation with a diode-pumped Cr:LiSAF laser.
AB  - We have created a broad spectrum spanning more than an optical octave by
      launching femtosecond pulses from a battery operated Cr:LiSAF laser into a
      photonic crystal fiber. Despite the massive broadening in the fiber, the comb
      structure of the spectrum is preserved, and this frequency comb is perfectly
      suited for applications in optical frequency metrology.

PMID- 18049615
TI  - Multiple four-wave mixing-induced modulational instability in highly birefringent
      fibers.
AB  - Theoretical and experimental results are presented that illustrate efficient
      generation of new optical frequencies by means of induced modulational
      instability in birefringent fibers for an initially highly phase-mismatched
      process. Modulational instability is assisted by multiple four-wave mixing
      interactions. This technique relaxes the strict spectral limitations imposed by
      the phase-matching conditions on the signal used for frequency conversion by
      means of modulational instability.

PMID- 18049616
TI  - Detection of multiregion objects embedded in nonoverlapping noise.
AB  - The concept of a statistical filter for objects that comprise several regions is
      introduced. The process is optimal in the presence of nonoverlapping noise for
      the target and may perform independently of variations in the mean value in every
      region. The basic performance of the filter is described, and a comparison with
      other types of processing is made.

PMID- 18049617
TI  - Time-to-frequency Fourier transformation with photon echoes.
AB  - We propose to use photon echoes in rare-earth-doped crystals to implement the
      Fourier-transform chirp algorithm. The process is considered for application to
      spectral analysis of fast radio-frequency signals. Compared with surface acoustic
      wave devices, the proposed scheme gives access to the larger bandwidths of rare
      earth-doped crystals and greater flexibility. An experimental demonstration of
      the proposed process is reported.

PMID- 18049618
TI  - Simple trace criterion for classification of multilayers.
AB  - The action of any lossless multilayer is described by a transfer matrix that can
      be factorized in terms of three basic matrices. We introduce a simple trace
      criterion that sorts the multilayers into three classes, each of whose properties
      are closely related to one (and only one) of the three basic matrices.

PMID- 18049619
TI  - Demonstration of a neonlike argon soft-x-ray laser with a picosecond-laser
      irradiated gas puff target.
AB  - We demonstrate a neonlike argon-ion x-ray laser, using a short-pulse laser
      irradiated gas puff target. The gas puff target was formed by pulsed injection of
      gas from a high-pressure solenoid valve through a nozzle in the form of a narrow
      slit and irradiated with a combination of long, 600-ps and short, 6-ps high-power
      laser pulses with a total of 10 J of energy in a traveling-wave excitation
      scheme. Lasing was observed on the 3p (1)S(0)?3s (1)P(1) transition at 46.9 nm
      and the 3d (1)P(1)?3p (1)P(1) transition at 45.1 nm. A gain of 11 cm(-1) was
      measured on these transitions for targets up to 0.9 cm long.

PMID- 18049620
TI  - Phase synchronization in coupled Nd:YAG lasers.
AB  - We investigate experimentally the transition to phase synchronization in coupled
      Nd:YAG lasers. As the coupling strength increases, the phase difference of two
      chaotic laser outputs develops from nonsynchronous to a phase-synchronous state
      via +/-2pi phase jumps. We analyze this transition.

PMID- 18049621
TI  - Reconstruction of blurred images by controlled formation of spatial solitons.
AB  - Diffracted digital images are reconstructed by excitation of spatial solitons in
      a bulk chi((2)) crystal, in the regime of single-pass parametric amplification of
      the quantum noise.

PMID- 18049622
TI  - Broadband infrared generation with noncollinear optical parametric processes on
      periodically poled LiNbO(3).
AB  - Broadband signal and idler generation based on the spectral retracing behavior in
      noncollinear phase matching of optical parametric generation in periodically
      poled LiNbO(3) (PPLN) is reported. Using PPLN of 29.5-mum quasi-phase-matching
      period and a Q-switched Nd:YAG laser as a pump, we obtained a broad signal
      spectrum from 1.66 to 1.96 mum and corresponding idler wavelengths from 2.328 to
      2.963 mum. The experimental results were consistent with theoretical predictions.
      Circular and elliptical pump beams were also compared.

PMID- 18049623
TI  - Periodic mode hopping induced by thermo-optic effects in continuous-wave optical
      parametric oscillators.
AB  - We show that thermal effects can lead to periodic mode hopping in cw optical
      parametric oscillators (OPOs). This mode hopping may occur as soon as two modes
      have different intensities at the point where they exchange their stability; this
      condition is easily fulfilled in OPOs that are triply resonant, or doubly
      resonant with a weakly resonant pump. We have observed such oscillations
      experimentally in a type II OPO in both configurations. A simple thermo-optic
      multimode model reproduces well the experimental regimes. We expect that
      multimode instabilities based on this mechanism can be observed with various
      aspects in many experimental setups at high pumping rate.

PMID- 18049624
TI  - Adaptative lensing driven by the radiation pressure of a continuous-wave laser
      wave upon a near-critical liquid liquid interface.
AB  - The bending of a liquid interface by the radiation pressure of a cw laser wave is
      generally weak. To strongly enhance the coupling, we investigate lensing in a
      near-critical phase-separated liquid mixture. By continuously tuning the softness
      of the meniscus by varying the temperature, we observed huge stationary interface
      deformations at low beam power that led to an important variation of the
      resultant soft lensing. We also illustrate the crucial role played by temperature
      in this process to demonstrate its potential use in lens adaptation.

PMID- 18049625
TI  - Energy transfer at optical frequencies to silicon-on-insulator structures.
AB  - The refractive-index distribution that is intrinsic to the silicon-on-insulator
      (SOI) material system makes it possible for optical-frequency guided waves to be
      confined by the SOI silicon layer. The same refractive-index distribution is
      unusual among nonmetals in that it is possible for those SOI guided waves to
      interact strongly with nearby optical-frequency radiators, absorbers, and
      scatterers (e.g., atoms, molecules, and nanoparticles). We calculate the guided
      mode excitation efficiency for an exterior particle near the SOI surface and show
      that it can attain values greater than 80% under appropriate conditions, thus
      showing that the SOI waveguide system is an attractive platform for the study of
      optical-frequency surface interactions.

PMID- 18049626
TI  - Pancharatnam--Berry phase in space-variant polarization-state manipulations with
      subwavelength gratings.
AB  - We report the appearance of a geometrical phase in space-variant polarization
      state manipulations. This phase is related to the classic Pancharatnam-Berry
      phase. We show a method with which to calculate it and experimentally demonstrate
      its effect, using subwavelength metal stripe space-variant gratings. The
      experiment is based on a unique grating for converting circularly polarized light
      at a wavelength of 10.6 mum into an azimuthally polarized beam. Our experimental
      evidence relies on analysis of far-field images of the resultant polarization.

PMID- 18049627
TI  - Compact transmission system using single-sideband modulation of light for quantum
      cryptography.
AB  - We report a new transmission that can be used for quantum key distribution. The
      system uses single-sideband-modulated light in an implementation of the BB84
      quantum cryptography protocol. The system is formed by two integrated unbalanced
      Mach-Zehnder interferometers and is based on interference between phase-modulated
      sidebands in the spectral domain. Experiments show that high interference
      visibility can be obtained.

PMID- 18049628
TI  - High-resolution Doppler-free molecular spectroscopy with a continuous-wave
      optical parametric oscillator.
AB  - We present a reliable, narrow-linewidth (100-kHz) continous-wave optical
      parametric oscillator (OPO) suitable for high-resolution spectroscopy
      applications. The singly resonant OPO with a resonated pump is based on
      periodically poled lithium niobate crystal and features a specially designed
      intracavity etalon, which permits precise tuning to any desired wavelength in a
      wide range. We demonstrate Doppler-free spectroscopy of a rovibrational
      transition of methane at 3.39 mum.

PMID- 18049629
TI  - Homodyne and heterodyne imaging through a scattering medium.
AB  - We introduce a novel two-dimensional (2D) homodyne and heterodyne technique for
      imaging objects through or embedded in a scattering medium. Our imaging approach
      is based on heterodyning of light with different Doppler broadenings that is
      scattered from objects of two different textures or from an opaque object and a
      textured scattering medium. We report on the initial demonstration of pulling
      signals out of noise for an object hidden behind a scattering medium.
      Enhancements of signal-to-noise ratio of the order of 50 have been achieved by
      use of a 2D holographic phase-sensitive detector. We also discuss the
      experimental feasibility of this approach for objects embedded in a scattering
      medium.

PMID- 18049630
TI  - Single-shot measurement of carrier-envelope phase changes by spectral
      interferometry.
AB  - We demonstrated single-shot measurements of spectral interference between a white
      light continuum generated in a hollow-fiber and its second harmonic. The
      interference has information on the carrier-envelope phase of an input pulse to
      the fiber and the time delay of the blue wing of the continuum. By analyzing the
      observed spectral interference, we estimated shot-by-shot changes of the carrier
      envelope phase. This method is useful for determining the carrier-envelope phase
      changes of a low-repetition-rate, high-intensity laser.

PMID- 18049631
TI  - Two-element-cavity femtosecond Cr(4+):YAG laser operating at a 2.6-GHz repetition
      rate.
AB  - A femtosecond Cr(4+):YAG laser with a simple two-element cavity was built. This
      laser typically attained a repetition rate of 2.64 GHz with a pulse width of 115
      fs at a center wavelength of 1540 nm. Output pulses were characterized by second
      harmonic generation frequency-resolved optical gating. Alignment of the two
      element cavity for mode-locked operation was easy; moreover, the cavity structure
      has the potential to produce an even higher repetition rate because one can
      miniaturize it simply by shortening a gain medium length.

PMID- 18049632
TI  - Ultrashort-laser-pulse measurement using swept beams.
AB  - We demonstrate a frequency-resolved optical gating (FROG) device that uses a
      sweepshot geometry that combines the advantages of multishot and single-shot
      pulse-measurement devices, has only one moving part, a galvanometer, and requires
      no computer control. Like a multishot device, it focuses the beam to a small spot
      (rather than a line focus) and has a high intensity in the nonlinear medium. Like
      single-shot devices, it makes measurements quickly, generating an entire FROG
      trace on a single camera screen (rather than requiring many camera downloads).

PMID- 18049633
TI  - Fundamental functions for ultrafast optical routing by temporal frequency-to
      space conversion.
AB  - We demonstrate fundamental functions for ultrafast optical routing by using an
      elemental part of an ultrafast optical technique for conversion of time to two
      dimensional space. A preliminary experimental result shows that recognition of
      header signals can be achieved at a rate of more than 600 Gbytes/s.

PMID- 18049634
TI  - Alloy-ceramic oxide multilayer mirrors for water-window soft x rays.
AB  - Alloy-ceramic oxide multilayers of Ni(80)Nb(20)- MgO with 3.56-nm period have
      been made by use of the pulsed-laser deposition technique and characterized by
      means of grazing-incidence x-ray reflectivity. The interface roughness was found
      to be only ~0.35 nm at the two interfaces, Ni(80)Nb(20)- MgO and MgO
      Ni(80)Nb(20), leading to a peak reflectivity of ~38% at the first order. The
      atomic structure in the two individual layers, Ni(80)Nb(20) and MgO, is found to
      be amorphous, in agreement with the deposition conditions. These multilayers can
      be used as mirrors for soft x rays in the angular range 18 degrees to 39 degrees
      , depending on the actual wavelength of radiation in the water-window region.

PMID- 18049635
TI  - Atomic spectral detection of tunable extreme ultraviolet pulses.
AB  - A novel method of detecting the spectral width and wavelength of extreme
      ultraviolet (XUV) pulses with a minimum number of experimental tools is
      demonstrated. The method relies on the photoionization probability of an atom as
      a function of the electric field. A tunable laser source in the XUV is used that
      is based on higher-harmonic generation of the frequency-doubled output of a 50-fs
      Ti:sapphire laser. The bandwidth and the wavelength of the seventh harmonic
      (~57nm) are detected with Ne, and the resolving power is lambda/Dlambda=10(5).

PMID- 18049636
TI  - Single-beam trapping in front of reflective surfaces.
AB  - We show that the optical trapping of dielectric particles by a single focused
      beam in front of a weakly reflective surface is considerably affected by
      interference of the incident and reflected beams, which creates a standing-wave
      component of the total field. We use the two-photon-excited fluorescence from a
      trapped dyed probe to detect changes in the distance between the trapped beam
      focus as the focus approaches the reflective surface. This procedure enables us
      to determine the relative strengths of the single-beam and the standing-wave
      trapping forces. We demonstrate that, even for reflection from a glass-water
      interface, standing-wave trapping dominates, as far as 5 mum from the surface.

PMID- 18049637
TI  - Fundamental-mode cutoff in a photonic crystal fiber with a depressed-index core.
AB  - We report a photonic crystal fiber with a depressed-index core doped with
      fluorine. The effective index of the cladding matches that of the core at an
      antiguiding wavelength, below which the fiber does not guide light at all.

PMID- 18049638
TI  - Polarization mode dispersion probability distribution for arbitrary distances.
AB  - The probability distribution of the differential group delay (DGD) at any fiber
      length is determined by use of a physically reasonable model of the fiber
      birefringence. We show that if the fiber correlation length is of the same order
      as or larger than the beat length, the DGD distribution approaches a Maxwellian
      in roughly 30 fiber correlation lengths, corresponding to a couple of kilometers
      in realistic cases. We also find that the probability distribution function of
      the polarization dispersion vector at the output of the fiber depends on the
      angle between it and the local birefringence vector on the Poincare sphere,
      showing that the DGD remains correlated with the orientation of the local
      birefringence axes over arbitrarily long distances.

PMID- 18049639
TI  - Soliton compression in Brillouin fiber lasers.
AB  - Pulse propagation in optical fibers may electrostrictively excite acoustic waves
      as a result of cladding Brillouin scattering, transversally propagating with
      respect to the fiber axis in the fiber's cladding, and mechanical coating. We
      show, for the first time to our knowledge, experimentally and theoretically that
      these transverse resonances within finite frequency ranges may cooperatively
      couple with the acoustic longitudinal modes of a fiber resonator, giving rise to
      stable trains of either spread or compressed three-wave Brillouin solitons and
      propose a first stability map for the rich four-wave dissipative dynamics.

PMID- 18049640
TI  - Neural network for three-dimensional object recognition based on digital
      holography.
AB  - We present a two-layer neural network for processing of three-dimensional (3D)
      images that are obtained by digital holography. The network is trained with a
      real 3D object to compute the weights of the layers. Experiments are presented to
      illustrate the system performance. The system is designed to detect a 3D object
      in the presence of various distortions. As an example, experiments are presented
      to illustrate how the system is able to recognize a 3D object with 360 degrees
      out-of-plane rotation.

PMID- 18049641
TI  - Three-dimensional display by use of integral photography with dynamically
      variable image planes.
AB  - A computer-generated integral photography system operating with a variable image
      plane is proposed. In this scheme, the gap between a lens array and a display
      panel is adjusted in real time. A synchronized elemental image array for real or
      virtual mode is integrated in front of or behind the lens array. This integration
      gives an observer an enhanced perception of depth. The proposed method can be
      applied to animated three-dimensional imaging.

PMID- 18049642
TI  - Laser relaxation-oscillation frequency imaging.
AB  - We describe a new imaging technique based on modification of laser relaxation
      frequency induced by coherent optical feedback from an external target. A direct
      comparison (both theoretical and experimental) is made with laser feedback
      interferometry techniques, in which there is a modification of the laser's steady
      state. We show that, for a laser with a cavity damping rate gamma(c) higher than
      the population damping rate, gamma(1) , the modification of the laser relaxation
      frequency can be several orders of magnitude more sensitive than the perturbation
      of the laser's output power. Application of this technique to imaging is
      reported.

PMID- 18049643
TI  - Secure communication scheme using chaotic laser diodes subject to incoherent
      optical feedback and incoherent optical injection.
AB  - We propose a secure communication scheme based on anticipating synchronization of
      two chaotic laser diodes, one subject to incoherent optical feedback and the
      other to incoherent optical injection. This scheme does not require fine tuning
      of the optical frequencies of both lasers as is the case for other schemes based
      on chaotic laser diodes subject to coherent optical feedback and injection. Our
      secure communication scheme is therefore attractive for experimental
      investigation.

PMID- 18049644
TI  - Stable route-tracking synchronization between two chaotically pulsing
      semiconductor lasers.
AB  - Stable route-tracking synchronization is experimentally demonstrated in two
      semiconductor lasers with delayed optoelectronic feedback. When the two lasers
      are stably synchronized, the receiver laser is observed to track the route to
      chaotic pulsing of the transmitter laser. The stability of the route-tracking
      synchronization is examined by calculation of the transverse Lyapunov exponents
      of the coupled system.

PMID- 18049645
TI  - Path-length distribution and path-length-resolved Doppler measurements of
      multiply scattered photons by use of low-coherence interferometry.
AB  - We report first results of measurements by low-coherence Doppler interferometry
      of the path-length distribution of photons undergoing multiple scattering in a
      highly turbid medium. We use a Mach-Zehnder interferometer with multimode graded
      index fibers and a superluminescent diode as the light source. The path-length
      distribution is obtained by recording of the heterodyne fluctuations that arise
      from the Brownian motion of particles in an Intralipid suspension as a function
      of the optical path length. The experimental path-length distribution is in good
      agreement with predictions of Monte Carlo simulations. In the heterodyne
      spectrum, an increase of the mean Doppler frequency with path length is observed.

PMID- 18049646
TI  - Micromachining of diamond with a near-field scanning optical microscope.
AB  - Direct-write laser micromachining of diamond on a submicrometer scale with a near
      field scanning optical microscope with an uncoated tapered fiber tip has been
      demonstrated. Micromachined structures can be imaged in situ immediately after
      modification of the sample. An early stage of the ablation process, which is
      believed to be conversion of diamond into graphite, has been visualized.

PMID- 18049647
TI  - Information transfer via cascaded collisions of vector solitons.
AB  - We demonstrate experimentally the transport of information from one vector
      (Manakov-like) spatial soliton to another via collisions with a third,
      intermediate soliton.

PMID- 18049648
TI  - Focal-shift formula in apodized nontelecentric focusing systems.
AB  - A single analytical formulation for evaluating the focal shift in any apodized
      nontelecentric focusing setup is reported. The formulation is also useful in the
      case of imaged paraxial beams. We show explicitly that the magnitude of the focal
      shift is determined by only one parameter that depends on the effective width of
      the pupil filter and its axial position. To illustrate our approach we examine
      different focusing setups.

PMID- 18049649
TI  - Photon antibunching in the fluorescence of a single dye molecule embedded in a
      thin polymer film.
AB  - We used scanning confocal microscopy to study the fluorescence from a single
      terrylene molecule embedded in a thin polymer film of polymethyl methacrylate, at
      room temperature, with a high signal-to-background ratio. The photon-pair
      correlation function g((2))(tau) exhibits perfect photon antibunching at tau = 0
      and a limit of 1.3, compatible with bunching associated with the molecular
      triplet state. Application of this molecular system to a triggered single-photon
      source based on single-molecule fluorescence is investigated.

PMID- 18049650
TI  - Frequency-dependent optical pumping in atomic ?-systems.
AB  - We consider the effects of optical pumping on the conversion of laser-frequency
      modulation into intensity modulation by an atomic absorption line in a vapor of
      alkali atoms driven in a ?-configuration. It is found that, due to optical
      pumping in combination with the excited-state hyperfine structure, the absorption
      line shape is distorted substantially as the Fourier frequency of the FM is
      changed. The most significant effect of the distortion is a shift of the apparent
      line center, which depends on how the frequency of the modulation compares with
      the optical pumping rate. This shift has implications for locking lasers to
      atomic transitions and also for FM-AM noise conversion in atomic vapors.

PMID- 18049651
TI  - Homodyne detection in spectral phase interferometry for direct electric-field
      reconstruction.
AB  - We study and demonstrate a version of spectral phase interferometry for direct
      electric-field reconstruction (SPIDER) that uses self-referencing homodyne
      detection. This technique has a higher sensitivity than conventional SPIDER, is
      self-calibrating, and can be adjusted for a wider range of pulse parameters.

PMID- 18049652
TI  - Terahertz reflection imaging using Kirchhoff migration.
AB  - We describe a new imaging method that uses single-cycle pulses of terahertz (THz)
      radiation. This technique emulates data-collection and image-processing
      procedures developed for geophysical prospecting and is made possible by the
      availability of fiber-coupled THz receiver antennas. We use a simple migration
      procedure to solve the inverse problem; this permits us to reconstruct the
      location and shape of targets. These results demonstrate the feasibility of the
      THz system as a test-bed for the exploration of new seismic processing methods
      involving complex model systems.

PMID- 18049653
TI  - Photonic device fabrication in glass by use of nonlinear materials processing
      with a femtosecond laser oscillator.
AB  - Single-mode X couplers and three-dimensional waveguides are fabricated in
      transparent glasses by use of an unamplified femtosecond laser generating
      energies of up to 100 nJ. Changing fabrication parameters such as power and
      scanning speed permits creation of waveguides with a wide range of structures and
      refractive-index difference. Optical coherence tomography shows large refractive
      index changes of up to ~10(-2) in the waveguides; these changes are consistent
      with guided mode analysis.

PMID- 18049654
TI  - Dispersion-managed soliton in a strong dispersion map limit.
AB  - A dispersion-managed optical system with stepwise periodic variation of
      dispersion is studied in a strong dispersion map limit in the framework of the
      path-averaged Gabitov-Turitsyn equation. The soliton solution is obtained by
      analytical and numerical iteration of the path-averaged equation. An efficient
      numerical algorithm for finding a DM soliton shape is developed. The envelope of
      soliton oscillating tails is found to decay exponentially in time, and the
      oscillations are described by a quadratic law.

PMID- 18049655
TI  - Differential-phase-to-intensity conversion based on injection locking of a
      semiconductor laser.
AB  - A novel method of optical phase-shift detection using differential-phase-to
      intensity conversion (DPIC) based on injection locking of a semiconductor laser
      is proposed. We predict DPIC numerically and verify it experimentally. We then
      demonstrate detection of OC-48 (2.48832-Gbit/s) phase-modulated signals by use of
      DPIC.

PMID- 18049656
TI  - Chemical sensing with microbent optical fiber.
AB  - We propose and demonstrate the possibility of using a permanently microbent bare
      optical fiber for detecting chemical species. Two detection schemes, viz., a
      bright-field detection scheme (for the core modes), and a dark-field detection
      scheme (for the cladding modes) have been employed to produce a fiber-optic
      sensor. The sensor described here is sensitive enough to detect concentrations as
      low as nanomoles per liter of a chemical species, with a dynamic range of more
      than 6 orders of magnitude.

PMID- 18049657
TI  - Analytical method for designing dispersion-managed fiber systems.
AB  - Using the equations of motion of pulse width and chirp, we present an analytical
      method for designing dispersion-managed (DM) fiber systems without optical
      losses. We show that the initial Gaussian pulse considered for the analytical
      design of periodically amplified DM fiber systems with losses will propagate as a
      proximity fixed point. Then averaging the DM soliton fields obtained from the
      slow dynamics of the proximity fixed point will yield the exact fixed point.

PMID- 18049658
TI  - Theory of self-focusing in photorefractive InP.
AB  - We present a theory of self-focusing and solitons in photorefractive InP,
      including the previously unexplained intensity resonance and the resonant
      enhancement of the space-charge field.

PMID- 18049659
TI  - Synthetic-aperture experiment in the visible with on-axis digital heterodyne
      holography.
AB  - We have developed a new on-axis digital holographic technique, heterodyne
      holography. The resolution of this technique is limited mainly by the amount of
      data recorded on two-dimensional photodetectors, i.e., the number of pixels and
      their size. We demonstrate that it is possible to increase the resolution
      linearly with the amount of recorded data by aperture synthesis as done in the
      radar technique but with an optical holographic field.

PMID- 18049660
TI  - Graded-index mid-infrared planar optical waveguides made from silver halides.
AB  - Since the index of refraction of AgCl(x)Br(1-x) (x<1) is higher than that of
      AgCl, by diffusing Br(-) ions into AgCl it was possible to control the index and
      thus obtain planar waveguides made from silver chlorobromide (AgClBr) on a AgCl
      substrate. Silver halides are transparent in the mid IR, and it was therefore
      possible to characterize the waveguides by transmission of 10.6-mum CO(2)-laser
      radiation through them. In a typical case, the thickness was optically measured
      and was found to be 65mum , and the propagation loss was 16 dB/cm. The output
      beam profile distribution was determined experimentally and found to be well
      correlated with a numerical analysis simulation based on a ray-tracing model of
      the eikonal equation. Planar waveguides that are transparent in the mid IR will
      likely be useful in numerous applications.

PMID- 18049661
TI  - Experimental observation of traveling waves in the transverse section of a laser.
AB  - The selection of a transverse traveling wave by an inhomogeneous pump profile has
      been experimentally observed in a class B laser structure. The laser structure
      consisted of a wide-aperture edge-emitting laser diode operating in pulsed mode
      to avoid thermal guiding effects. The injection current's profile was modified
      from the usual top-hat configuration to a Lorentzian-like profile by the
      inclusion of a 10-mum p-type expitaxial spreading layer. Spatial dependance of
      the far field on the near field was observed. The same behavior is also
      demonstrated numerically by use of Maxwell-Bloch equations for semiconductor
      lasers.

PMID- 18049662
TI  - Fiber laser mode locked by a Sagnac interferometer with nonlinear polarization
      rotation.
AB  - We describe a new fiber laser configuration based on a nonlinear optical loop
      mirror with a symmetrical coupler, a quarter-wave retarder, and highly twisted,
      birefringent fiber in the loop. The nonlinear optical loop mirror configuration
      operates by nonlinear polarization rotation. We have achieved stable generation
      of subpicosecond pulses with milliwatts of average output power.

PMID- 18049663
TI  - Reducing the linewidth of a diode laser below 30 Hz by stabilization to a
      reference cavity with a finesse above 10(5).
AB  - An extended-cavity diode laser operating in the Littrow configuration emitting
      near 657 nm is stabilized through its injection current to a reference cavity
      with a finesse of more than 10(5) and a corresponding resonance linewidth of 14
      kHz. The laser linewidth is reduced from a few megahertz to a value below 30 Hz.
      The compact and robust setup appears ideal as a portable optical frequency
      standard that uses the calcium intercombination line.

PMID- 18049664
TI  - High-peak-power diode-pumped Nd:YAG laser with a Brillouin phase-conjugation-
      pulse-compression mirror.
AB  - We demonstrate stimulated Brillouin scattering compression of diode-pumped Nd:YAG
      laser pulses with a 3-ns duration into 350-ps pulses at a pulse-repetition rate
      of 100 Hz for what is believed to be the first time. The output pulse energy was
      6.5 mJ, with a beam-quality factor M(2) of 1.15, and after final amplification
      the energy reached 36 mJ, with M(2) of 2.5.

PMID- 18049665
TI  - Rapid temperature tuning of a 1.4-mum diode laser with application to high
      pressure H(2)O absorption spectroscopy.
AB  - Enhanced wavelength tuning of a distributed-feedback InGaAsP diode laser is
      demonstrated by use of rapid temperature cycling. The laser-active region is
      cycled from -10 to +50 degrees C (scanning the output from 1399 to 1403 nm) at
      kilohertz rates by pulsed heating with an auxiliary 532-nm laser. Such 4-nm scans
      represent a ten-fold increase in the wavelength-scanning range offered by
      standard current-tuning techniques and thus extend the capabilities of scan
      wavelength sensors and systems. As an example application, we demonstrate
      absorption spectroscopy of H(2)O vapor at a pressure of 10 atm.

PMID- 18049666
TI  - Influence of the phase function on determination of the optical properties of
      biological tissue by spatially resolved reflectance.
AB  - Spatially resolved reflectance measurements are widely used for determination of
      the optical properties of biological media. However, the influence of the phase
      function on these measurements has not been quantified. We show that errors in
      the derived reduced scattering and absorption coefficients are as great as 100%
      for both absolute and relative spatially resolved reflectance measurements if a
      standard solution of the diffusion equation is used in the analysis. In addition,
      we investigated nonlinear regressions, using Monte Carlo simulations and an
      additional fitting parameter that characterizes the phase function, and found
      that the errors in the obtained optical coefficients were </=20% .

PMID- 18049667
TI  - Spatial solitons in a pumped semiconductor resonator.
AB  - Bright and dark spatial solitons are observed in an optically pumped
      semiconductor resonator. The pumping allows us to reduce considerably the light
      intensity necessary for the existence of the solitons and alleviates thermal load
      problems. Experiments are found to agree qualitatively with calculations based on
      a simple large-aperture semiconductor resonator model. The role of the signs of
      the absorptive and reactive nonlinearities in soliton existence is discussed in
      relation to the nonlinear resonance effect, the tilted-wave mechanism of pattern
      formation, and the sign of the population inversion.

PMID- 18049668
TI  - Collisions between (2+1)D rotating propeller solitons.
AB  - We study theoretically the collisions between (2+1)D rotating-dipole-type bimodal
      solitons and find that such interactions exhibit many interesting exchanges of
      angular momentum.

PMID- 18049669
TI  - Ultraviolet upconversion in thulium-doped fluorozirconate fiber observed under
      two-color excitation.
AB  - Ultraviolet upconversion signals at 293, 351, and 366 nm were observed from
      thulium-doped fluorozirconate fiber pumped with a 458-nm Ar(+) laser. The
      upconversion signal's intensity was enhanced 5x when the fiber was simultaneously
      pumped with a 458-nm Ar(+) laser and a 585-nm dye laser. There is evidence of the
      formation of defect centers under simultaneous excitation by visible and near
      infrared lasers (458 and 750 nm), and there is no evidence of color-center
      formation when both of the exciting beams are in the visible (458 and 585 nm).

PMID- 18049670
TI  - Continuous-wave-pumped Raman-assisted fiber optical parametric amplifier and
      wavelength converter in conventional dispersion-shifted fiber.
AB  - We present a continuous-wave-pumped fiber optical parametric amplifier, operating
      near 1539 nm in conventional dispersion-shifted fiber, with maximum on-off gain
      and wavelength-conversion efficiency of 13.7 and 13.1 dB, respectively. In
      addition, we show a novel configuration based on Raman amplification assistance
      in the parametric gain fiber that further increases the gain and wavelength
      conversion efficiencies to 16.7 and 16.2 dB, respectively.

PMID- 18049671
TI  - Gallium-diffused waveguides in sapphire.
AB  - The fabrication and characterization of gallium-diffused planar waveguides in
      sapphire are reported. Waveguides were fabricated by diffusion of 60-200-nm-thick
      films of gallium oxide into c -cut sapphire at 1600 degrees C for times ranging
      from 6 to 16 h. Near-field intensity profiles of the guided modes were measured
      at wavelengths from 488 to 850 nm, and the surface-index elevation was estimated
      to be up to (0.6+/-0.02)x10(-2) . Potential applications for low-threshold
      Ti:sapphire waveguide lasers and for optical integrated circuits with passive and
      active elements in sapphire are discussed.

PMID- 18049672
TI  - Absolute frequency measurement of the 435.5-nm (171)Yb+-clock transition with a
      Kerr-lens mode-locked femtosecond laser.
AB  - We have measured the frequency of the 6s(2)S(1/2)(2)-5d D(3/2)(2) electric
      quadrupole transition of (171)(Yb) (+) with a relative uncertainty of 1x10(-14) ,
      nu(Yb)=688358 979309312Hz +/-6Hz . We used a femtosecond frequency comb generator
      to phase-coherently link the optical frequency derived from a single trapped ion
      to a cesium-fountain-controlled hydrogen maser. This measurement is one of the
      most accurate measurements of optical frequencies ever reported, and it
      represents a contribution to the development of optical clocks based on a
      (171)Yb(+)-ion standard.

PMID- 18049673
TI  - Optimization of ultrashort-pulse squeezing by spectral filtering with the Fourier
      pulse-shaping technique.
AB  - We propose an adaptive waveform-control approach to optimize photon-number
      squeezing by the nonlinear fiber spectral filtering method. More than -8-dB
      squeezing of the sech envelope pulse is numerically predicted when the spectral
      phase is modulated before the pulse is sent to a fiber. The quantum cross
      correlations of the photon-number fluctuation become uniformly negative when the
      pulse is optimally shaped.

PMID- 18049674
TI  - Far-field radiation from quantum boxes located in pillar microcavities.
AB  - Far-field radiation for quantum boxes located in pillar microcavities was
      investigated spatially and spectrally at room temperature. We have found that
      small-diameter pillars show directional emission for the fundamental cavity mode
      together with a spectral behavior dominated by the pillar's discrete modal
      structure. These results may be important in the context of single-photon
      emitters for quantum communications.

PMID- 18049675
TI  - Validity of the paraxial approximation in the focal region of a small-f-number
      lens.
AB  - For small- f -number lenses, whereas the paraxial approximation cannot be used
      for a description of propagation of light from the lens to the focal region, it
      is shown that the approximation is still valid for propagation of light over
      relatively small distances in the region near the focus.

PMID- 18049676
TI  - Vortex revivals with trapped light.
AB  - We predict that vortex dipoles nested in light beams trapped in graded-index
      media can undergo closed Berry trajectories, yielding periodic vortex
      annihilations and revivals along the light-propagation direction. The vortex
      revivals from vortex-free wave fronts are mediated by Freund stationary point
      bundles that carry the necessary Poincare-Hopf indices. Vortex spiraling and
      spontaneous generation of circular-edge dislocations are also found to occur.

PMID- 18049677
TI  - Selective transparency of single-mode waveguides with surface scattering.
AB  - Random surface scattering in a one-mode waveguide is studied for a surface
      profile that has long-range correlations along the waveguide. Analytical
      treatment of this scattering shows that, with the proper choice of surface, one
      can arrange any desired combination of transparent and nontransparent frequency
      windows. We suggest a method for finding such profiles and demonstrate its
      effectiveness by making use of direct numerical simulations.

PMID- 18049678
TI  - Fourth- and sixth-order polarization aberrations of antireflection-coated optical
      surfaces.
AB  - For single-layer antireflection-coated (ARC) optical surfaces, the first five
      derivatives of reflectance with respect to angle of incidence phi for the p and s
      polarizations are zero at normal incidence, whereas the first three derivatives
      of differential transmission phase shift D(t)(= D(tp)-D(ts)) with respect to phi
      are also zero at phi=0 . Consequently, ARC optical systems with numerical
      apertures of <0.7(phi<45 degrees ) exhibit fourth- and sixth-order polarization
      aberrations owing to retardance and diattenuation, respectively. Results for ARC
      Ge and ZnS surfaces are presented to illustrate these effects.

PMID- 18049679
TI  - Photoacoustic monitoring of trace gases by use of a diode-based difference
      frequency laser source.
AB  - We present a compact mid-infrared laser spectrometer for trace-gas monitoring.
      Difference frequency generation in periodically poled LiNbO(3) is used as laser
      source, yielding a tuning range 3.2-3.7mum at a linewidth of 154 MHz. The
      relatively high average power of 3 to 5 mW favors detection with a small resonant
      photoacoustic gas cell. Measurements of methane yield a detection limit in the
      low parts in 10(6) by volume concentration range.

PMID- 18049680
TI  - Single-shot spectral interferometry with chirped pulses.
AB  - We present a method for obtaining time-resolved measurements of the amplitude
      modulation and the phase shift of a chirped probe pulse interacting with a
      femtosecond-laser-produced plasma. Based on spectral interferometry, the
      technique allows for single-shot measurements and keeps the temporal resolution
      associated with the full bandwidth of the probe pulse. We demonstrate the
      efficiency of this technique by probing femtosecond-laser breakdown of plastic
      targets.

PMID- 18049681
TI  - All-optical square-pulse generation and multiplication at 1.5 mum by use of a
      novel class of fiber Bragg gratings.
AB  - A new class of linearly chirped fiber Bragg gratings, suitable for all-fiber
      optical multiplication and reshaping of picosecond pulse trains, is proposed and
      experimentally demonstrated. Repetition-rate multiplication, based on the
      temporal Talbot effect, is achieved by accurate control of the grating chirp, and
      a suitable design of the index-modulation depth profile allows for simultaneous
      square-pulse shaping. A 50-ps squarelike optical pulse train at 10-GHz repetition
      rate is obtained, starting from a 2.5-GHz Gaussian pulse train emitted by a mode
      locked Er-Yb laser.

PMID- 18049682
TI  - Monitoring the ultrafast electric field change at a mid-infrared plasma Bragg
      mirror.
AB  - The electric field change of a femtosecond mid-infrared (MIR) pulse reflected by
      a new type of Bragg mirror is directly measured by time-resolved cross
      correlation spectroscopy. The refractive-index contrast of the plasma Bragg
      mirror is achieved by use of different doping levels of only one type of
      semiconductor material (n(+) -doped GaAs and undoped GaAs). The direct
      measurement of the time dependence of the electric field of a reflected MIR pulse
      permits the observation of a noninstantaneous response of a Bragg mirror compared
      with a metallic surface, which is due to the penetration of the pulse into the
      multilayer structure.

PMID- 18049683
TI  - ?erenkov-based radiation from superluminal excitation in microdroplets by
      ultrashort pulses.
AB  - We demonstrate from a generalized Lorenz-Mie theory that ultrashort pulses can
      induce superluminal excitation in microdroplets. A ?erenkov-like effect can thus
      be expected for sufficiently intense ultrashort pulses.

PMID- 18049684
TI  - Three-dimensional cooling of cesium atoms in a reflecting copper cylinder.
AB  - We present what is to our knowledge the first observation of spin-polarized atoms
      cooled within a reflecting cylinder in a high-power medium. A low-pressure vapor
      of cesium atoms is stored in a glass cell whose volume is 58 cm(3). Cooling laser
      light (lambda=852 nm) is injected into the cell by optical fibers and is recycled
      by multiple reflections from the walls of the cylinder. The technique used in
      this experiment greatly simplifies the generation of laser-cooled atoms. A
      maximum of 2.5 x 10(8) cold atoms was detected by a time-of-flight technique. The
      damping of atomic motion has lead to temperatures as low as 3.5muK .

PMID- 18049685
TI  - Antireflection microstructures fabricated upon fluorine-doped SiO(2) films.
AB  - Two-dimensional periodic structures were fabricated upon a fluorine-doped SiO(2)
      film in which the fluorine content changed gradually in the direction of film
      thickness. The films were deposited by plasma-enhanced chemical-vapor deposition.
      The film was periodically patterned into a 1-mum period and an ~1-mum -groove
      depth by inductive coupled plasma reactive-ion etching followed by chemical
      etching in a diluted HF solution. A surface reflectance of 0.7% was attained at
      1.85-mum wavelength, a value that is one fifth as large as the 3.5% Fresnel
      reflection of a SiO(2) substrate with a flat surface.

PMID- 18049686
TI  - Transform spectrometer based on measuring the periodicity of Talbot self-images.
AB  - We demonstrate a compact transform spectrometer based on measuring the
      periodicity of Talbot self-images. The system has no moving parts; it contains
      only a tilted absorption grating that is imaged onto a CCD camera. The linear
      architecture of the system makes it possible to use this design in imaging arrays
      of spectrometers. Unlike other transform spectrometers, its resolution is
      independent of wavelength.

PMID- 18049687
TI  - Synthesis of diffractive axicons for partially coherent light based on asymptotic
      wave theory.
AB  - A general, noniterative method for designing diffractive axicons is derived. This
      new technique clarifies the earlier phenomenological design principle that was
      used for coherent light and extends it to the domain of partial coherence. The
      approach is based on the method of stationary phase in fluctuating diffracted
      wave fields, and it applies to arbitrary axially symmetric radiation of the
      Schell-model type. It is shown that the general design equation can be solved
      numerically, in a straightforward way, for any reasonable illumination and image
      specifications.

PMID- 18049688
TI  - Polarizing diffraction-grating triplicators.
AB  - We report experimental results with a reflective continuous anisotropic
      polarizing diffraction-grating beam splitter that produces three diffraction
      orders. The diffraction efficiencies and polarizations of the diffracted orders
      are controlled through the incoming polarization state and by use of a wave plate
      with arbitrary orientation located between the grating and a mirror. In
      particular, we show experimental evidence of a diffraction triplicator-a 100%
      efficiency diffractive device that generates three orders with equal power.

PMID- 18049689
TI  - Group velocity of solitons.
AB  - It is shown that, in addition to the well-known phase accumulation of a traveling
      soliton, which may be interpreted as a change of phase velocity as a result of
      the Kerr nonlinearity, there is a change in the speed of travel of the envelope,
      the group velocity. This analysis is extended to dispersion-managed solitons, for
      which it is shown that the discrepancy between phase- and group-velocity changes
      is generally smaller.

PMID- 18049690
TI  - Residual stress relaxation in the core of optical fiber by CO(2) laser
      irradiation.
AB  - We observed residual stress relaxation by CO(2) laser irradiation in the cores of
      optical fibers by direct stress measurement. It was demonstrated that the
      mechanical stress was fully relaxed by CO(2) laser irradiation and that the
      remaining stress in the core was thermal stress that was due to a mismatch of the
      thermal expansion coefficients of the fiber core and cladding. The net core
      stresses after relaxation were 17, 68, and 203 MPa in Ge-B-codoped fibers drawn
      at 0.53, 1.38, and 3.48 N, respectively. Changes in the refractive indices of the
      cores as a result of residual stress relaxation were also estimated.

PMID- 18049691
TI  - Confinement losses in microstructured optical fibers.
AB  - We describe a multipole formulation that can be used for high-accuracy
      calculations of the full complex propagation constant of a microstructured
      optical fiber with a finite number of holes. We show how the imaginary part of
      the microstructure, which describes confinement losses not associated with
      absorption, varies with hole size, the number of rings of holes, and wavelength,
      and give the minimum number of rings of holes required for a specific loss for
      given parameters.

PMID- 18049692
TI  - Dependence of Gordon-Haus timing jitter on the ratio of the forward and backward
      pump powers.
AB  - The Gordon-Haus timing jitter of optical pulses in dispersion-managed
      communication systems with distributed amplification is studied. The jitter
      penalty for equal forward and backward pump powers and a pump spacing of 100 km
      is almost 9 dB lower than the jitter penalty for lumped amplification and an
      amplifier spacing of 100 km.

PMID- 18049693
TI  - High-frame-rate joint Fourier-transform correlator based on Sn(2)P(2)S(6)
      crystal.
AB  - We present a joint Fourier-transform correlator working at a 10-kHz repetition
      rate. It is based on a photorefractive Sn(2)P(2)S(6) crystal operated in the
      pulsed direct band-to-band photoexcitation regime at a wavelength of 532 nm and a
      pulse length of 50 ns. The intersection of two plane waves with a total pulse
      fluence of 100muJ/cm(2) results in a buildup of thin dynamic holograms to a
      typical diffraction efficiency of 10(-4) in a time of ~1mus and decay again in
      less than 10mus . The correlator was tested by a fast image sequence generated by
      the pulsed readout of a holographic memory system. Successful correlation at a
      rate of 10 kHz has already been achieved for a pulse energy of only 200 nJ in the
      template images.

PMID- 18049694
TI  - Thermal effects in a dual-clad ytterbium fiber laser.
AB  - We present experimental results of temperature tuning in a dual-clad ytterbium
      fiber laser. We varied the temperature of the fiber from 0 to 100 degrees C and
      found significant changes in operating wavelength, power, and threshold. Over
      this range, the wavelength shifted at a rate of 0.2 nm/ degrees C, and the lasing
      threshold increased by a factor of 2.

PMID- 18049695
TI  - Yb:YAG power oscillator with high brightness and linear polarization.
AB  - A diode-pumped Yb:YAG laser with a novel end-pumped zigzag slab architecture has
      been developed. This architecture provides uniform transverse pump profiles,
      conduction cooling of the laser crystal, mechanical robustness, and ready
      scalability to higher powers. At room temperature the laser emits 415 W of cw
      power with 30% optical conversion efficiency. An image-inverting stable resonator
      permits a high-brightness output of 252 W with linear polarization and an average
      M(2) beam quality of 1.45. Q-switched pulse energies of as much as 20 mJ and
      average Q<i/>-switched powers of as much as 150 W were obtained while M(2) was
      maintained at <1.5.

PMID- 18049696
TI  - Room-temperature Tm, Ho:LuLiF(4) laser with a novel quasi-end-pumping technique.
AB  - A novel diode-pumped, efficient, quasi-end-pumping scheme that uses two lens
      ducts to achieve homogeneous pumping in a gain medium was proposed and evaluated.
      With this technique, room-temperature laser action at a pulse repetition
      frequency up to 20 Hz was demonstrated in 5%Tm, 0.5%Ho:LuLiF(4), which we grew by
      the Czochralski method. At 10 Hz a long-pulse laser output energy in excess of 24
      mJ and a slope efficiency with respect to the incident pump energy of 10.7% were
      obtained.

PMID- 18049697
TI  - Laser emission in highly doped Nd:YAG crystals under (4)F(5/2) and (4)F(3/2)
      pumping.
AB  - A comparison of laser emission in highly doped (2.4-and 3.5-at. %) Nd:YAG
      crystals is made for conventional 808-nm pumping in F(5/2)(4) and resonant
      pumping at 885 nm in the band that collects the hot transitions Z(2)?R(1) and
      Z(3)?R(2) of I(9/2)(4)?F(3/2)(4) absorption. A systematic improvement of the
      laser parameters (slope efficiency and emission threshold) in absorbed power
      under hot-band pumping is observed, as expected from the reduction of the pump's
      quantum defect. Together with the expected reduction of heat generation, resonant
      hot-band pumping in concentrated components shows prospect for greatly increasing
      the emission capabilities of the Nd:YAG lasers.

PMID- 18049698
TI  - Ultrashort-laser-pulse-induced persistent spectral hole burning of Eu(3+) in
      sodium borate glasses.
AB  - We have observed persistent spectral hole burning (PSHB) in Eu(3+) -doped sodium
      borate glasses irradiated with near-IR femtosecond laser pulses. As-prepared
      glasses, i.e., glasses melted in air, do not show PSHB even at low temperatures
      (~77K) , but room-temperature PSHB occurs in the irradiated glasses. The exposure
      to IR radiation causes both the reduction of Eu(3+) to Eu(2+) and the formation
      of intrinsic defects. We propose that the photoinduced redistribution of electric
      charges between Eu(3+) to Eu(2+) is responsible for the occurrence of PSHB.

PMID- 18049699
TI  - Multiple-objective microscopy with three-dimensional resolution near 100 nm and a
      long working distance.
AB  - The resolution of microscopes is limited by the sizes of their point-spread
      functions. The invention of confocal, theta, and 4Pi microscopes has permitted
      the classic Abbe limit to be exceeded. We propose the use of a combination of 4Pi
      and theta microscopy to decrease resolution by using four illumination objectives
      and two detection objectives. Using middle numerical aperture, long-working
      distance objectives yielded a resolution near 100 nm in the three dimensions,
      which opens the possibility of exploring large volumes with a high resolution.

PMID- 18049700
TI  - Second-harmonic generation in a near-field optical-fiber probe.
AB  - Second-harmonic generation (SHG) in a near-field optical-fiber probe was
      observed. The tip of the probe consists of a triple-tapered fiber with an
      aluminum coating. For a fiber probe with an aperture size of 100 nm, the SHG
      conversion factor was 2.0 x 10(-11)cm(2)/W , which is as large as that of a 5-mm
      KDP crystal. In a probe-to-probe experiment, we demonstrated that SHG took place
      at the aluminum coating on the fiber probe.

PMID- 18049701
TI  - Signal readdressing by steering of spatial solitons in bulk nematic liquid
      crystals.
AB  - Fully three-dimensional spatial solitons in bulk nematic liquid crystals form
      self-consistent waveguides that are able to confine a weak, collinear copolarized
      signal at different wavelengths and with large trapping angles. We use a
      milliwatt cw source to generate a soliton and, by angular steering of the
      soliton, spatially readdress the guided signal.

PMID- 18049702
TI  - Periodically poled BaMgF(4) for ultraviolet frequency generation.
AB  - Ferroelectric domain inversion has been demonstrated in BaMgF(4) . Transparency
      has been measured to <140nm, and no change in transmission was measured under 157
      nm irradiation for >1.1x10(9) shots at 2mJ/cm(2) per pulse. First-order quasi
      phase-matched generation of 157 nm is predicted by use of grating periods as long
      as 1.5mum. This material should permit shorter-wavelength chi((2)) frequency
      mixing processes than with any other crystalline material.

PMID- 18049703
TI  - Compensation for self-focusing by use of cascade quadratic nonlinearity.
AB  - We demonstrate theoretically and experimentally compensation for positive Kerr
      phase shifts with negative phases generated by cascade quadratic processes.
      Experiments show correction of small-scale self-focusing and whole-beam self
      focusing in the spatial domain and self-phase modulation in the temporal domain.

PMID- 18049704
TI  - Theoretical upper limits and experimental overestimates for molecular
      hyperpolarizabilities: a symbiosis.
AB  - A recently developed theory concerning the physical limits on optical
      hyperpolarizabilities is shown to be useful in the theoretical prediction of
      contributions of multiphoton fluorescence to experimentally determined
      hyperpolarizability values. Recent experimental results are compared with the
      theoretical limit. Without correction for the fluorescence contribution, results
      for the first hyperpolarizability in the forbidden region can be obtained. Proper
      correction of the systematic error shifts these values to the theoretical limit.
      Hence, experimental values above the theoretical upper limit should be suspect,
      but an appropriate fluorescence suppression technique is available. Reversing the
      argument, the observation that artificially overestimated values for the first
      hyperpolarizability are reduced from the forbidden region to exactly this upper
      limit is found to corroborate the limiting theory.

PMID- 18049705
TI  - Reflection-type polarization holograms in bacteriorhodopsin films for low-light
      recording.
AB  - Reflection-type polarization holograms with phase-conjugated readout are very
      useful for low-light recording with bacteriorhodopsin (BR) films. The dependence
      of reflection-type holograms with parallel and orthogonal recording beams on
      their intensity ratio (1:1-1:20) was investigated. It was found that for
      orthogonally polarized beams the phase-conjugated signal depends significantly
      less on the beam intensity ratio than predicted by coupled-wave theory. This
      finding is of particular relevance for recording of very low object-beam
      intensities with BR films, e.g., in interferometry, where signals with a high
      signal-to-noise ratio, owing to the different polarizations of the scattered
      light and the signal, and with low dependence of the diffraction efficiency on
      the ratio between the reference and object-beam intensities are obtained. With
      this asymmetric recording process, holograms were recorded successfully in BR
      films with a good signal-to-noise ratio at exposures (from the object side) as
      low as 50muJ/cm(2) . These exposures are in the range of those typically used for
      silver halide films.

PMID- 18049707
TI  - Propagation of nonparaxial beams with a modified Arnoldi method.
AB  - We have developed a modified Arnoldi method that includes a complex square-root
      approximation, which excels at modeling the propagation of highly diverging beams
      in various media. Simulations of one transverse dimensional beam with an
      ultranarrow width and of cylindrical Gaussian beams with various divergence
      angles reveal the strength of this nonparaxial-beam propagation method.

PMID- 18049706
TI  - Near fields and far fields generated by sources in the presence of dielectric
      structures with cylindrical symmetry.
AB  - A full-vectorial integral equation method is presented for calculating near
      fields and far fields generated by sources in the presence of general finite
      sized dielectric structures with cylindrical symmetry. The method is relevant for
      modeling of a class of antenna designs and some optical components with
      cylindrical symmetry, e.g., vertical-cavity surface-emitting lasers, microdisk
      lasers, and light-emitting diodes.

PMID- 18049708
TI  - Spatial Fourier-transform polarimetry using space-variant subwavelength metal
      stripe polarizers.
AB  - A novel method for rapid polarization measurement is suggested. The method is
      based on a periodic space-variant polarizer that can be realized by use of
      subwavelength metal-stripe gratings. The Stokes parameters of the incident beam
      are determined by Fourier analysis of the space-variant intensity transmitted
      through the grating, thus permitting real-time polarization measurement. We
      discuss the design and realization of such polarizers and demonstrate our
      technique with polarization measurements of CO(2)-laser radiation at a wavelength
      of 10.6mum.

PMID- 18049709
TI  - Ultrasensitive pulsed, balanced homodyne detector: application to time-domain
      quantum measurements.
AB  - A pulsed, balanced homodyne detector has been developed for precise measurement
      of the electric field quadratures of pulsed optical quantum states. A high level
      of common mode suppression (>85 dB) and low electronic noise (730 electrons per
      pulse) provide a signal-to-noise ratio of 14 dB for measurement of the quantum
      noise of individual pulses. Measurements at repetition rates as high as 1 MHz are
      possible. As a test, quantum tomography of the coherent state was performed, and
      the Wigner function and the density matrix were reconstructed with 99.5%
      fidelity. The detection system can be used for ultrarsensitive balanced detection
      in cw mode, e.g., for weak absorption measurements.

PMID- 18049710
TI  - Ellipsometric measurements by use of photon pairs generated by spontaneous
      parametric downconversion.
AB  - We present a novel interferometric technique for performing ellipsometric
      measurements. This technique relies on the use of a nonclassical optical source,
      namely, polarization-entangled twin photons generated by spontaneous parametric
      downconversion from a nonlinear crystal, in conjunction with a coincidence
      detection scheme. Ellipsometric measurements acquired with this scheme are
      absolute; i.e., they do not require source and detector calibration.

PMID- 18049711
TI  - Amplitude-squeezed emission from a transverse single-mode vertical-cavity surface
      emitting laser with weakly anticorrelated polarization modes.
AB  - We discuss the polarization-resolved intensity noise characteristics of a
      transverse single-mode vertical-cavity surface-emitting laser (VCSEL).
      Measurements by a sensitivity-enhanced lock-in amplifier detection scheme yield
      only an imperfect anticorrelation between the strong and the weak orthogonally
      polarized fundamental modes. Yet the total emission shows amplitude squeezing of
      0.4 dB below the shot-noise level. Unlike for transverse two-mode emission, a
      perfect anticorrelation between the two polarization modes is not necessary for
      generation of amplitude-squeezed emission in a transverse single-mode VCSEL, in
      agreement with theoretical predictions.

PMID- 18049712
TI  - Diode-pumped Kerr-lens mode-locked Yb:KY(WO(4))(2) laser.
AB  - A self-starting Kerr-lens mode-locked Yb:KY(WO(4))(2) laser directly end pumped
      by two 1.6-W diodes is demonstrated for what is to our knowledge the first time.
      Pulses as short as 71 fs with 120-mW average output power, at a center wavelength
      of 1057 nm, were obtained at a repetition rate of 110 MHz. A 10-nm tuning range
      was achieved with longer pulses and higher average output power.

PMID- 18049713
TI  - Structural changes in fused silica after exposure to focused femtosecond laser
      pulses.
AB  - Using in situ Raman scattering in a confocal microscopy setup, we have observed
      changes in the network structure of fused silica after modifying regions inside
      the glass with tightly focused 800-nm 130-fs laser pulses at fluences of 5-200 J
      cm(-2). The Raman spectra show a large increase in the peaks at 490 and 605cm(
      1), owing to 4- and 3-membered ring structures in the silica network, indicating
      that densification occurs after exposure to the femtosecond laser pulses. The
      results are consistent with the formation of a localized plasma by the laser
      pulse and a subsequent microexplosion inside the glass.

PMID- 18049714
TI  - Phase-locked, time-delayed, harmonic pulses for high spectral resolution in the
      extreme ultraviolet: errata.

PMID- 18049715
TI  - Differential regulation of neuregulin 1 expression by progesterone in astrocytes
      and neurons.
AB  - Glial-neuronal interactions are crucial processes in neuromodulation and synaptic
      plasticity. The neuregulin 1 family of growth and differentiation factors have
      been implicated as bidirectional signaling molecules that are involved in
      mediating some of these interactions. We have shown previously that neuregulin 1
      expression is regulated by the gonadal hormones progesterone and 17beta-estradiol
      in the CNS, which might represent a novel, indirect mechanism of the
      neuromodulatory actions of these gonadal hormones. In the present study, we
      sought to determine the effects of progesterone and 17beta-estradiol on
      neuregulin 1 expression in rat cortical astrocytes and neurons in vitro. We
      observed that progesterone increased the expression of neuregulin 1 mRNA and
      protein in a dose-dependent manner in cultured astrocytes, which was blocked by
      the progesterone receptor antagonist RU-486. In contrast, 17beta-estradiol did
      not increase either neuregulin 1 mRNA or protein in astrocytes. We observed no
      effect of either progesterone or 17beta-estradiol on neuregulin 1 mRNA and
      protein in rat cortical neurons in vitro. Finally, we observed that treatment of
      cortical neurons with recombinant NRG1-beta1 caused PSD-95 to localize in puncta
      similar to that observed following treatment with astrocyte-conditioned medium.
      These results demonstrate that progesterone regulates neuregulin 1 expression,
      principally in astrocytes. This might represent a novel mechanism of progesterone
      mediated modulation of neurotransmission through the regulation of astrocyte
      derived neuregulin 1.

PMID- 18049716
TI  - Laterality in Maternal Cradling and Infant Positional Biases: Implications for
      the Development and Evolution of Hand Preferences in Nonhuman Primates.
AB  - Left-sided maternal cradling has been widely reported in human populations. In
      this paper, I review the evidence of laterality in maternal cradling and infant
      positional biases in non-human primates. The review revealed some evidence of
      population-left sided cradling in great apes but little consistency in bias was
      found among Old and New World monkeys. Very little data have been reported in
      prosimians. I further describe how asymmetries in either maternal cradling or
      infant positional biases may explain individual and species differences in hand
      preference.

PMID- 18049717
TI  - Potential Role of the AMP-activated Protein Kinase in Regulation of Insulin
      Action.
AB  - Because of the predominant role of skeletal muscle in insulin-stimulated
      clearance of blood glucose, understanding mechanisms for increasing the ability
      of muscle to respond to insulin could potentially lead to novel strategies for
      treatment or prevention of diabetes. Recently, the AMP activated protein kinase
      (AMPK) has emerged as a promising candidate for potentiation of insulin action.
      Several antidiabetic drugs have been shown to activate AMPK, cellular stresses
      such as exercise that increase AMPK activity also increase insulin action, and
      several downstream targets of AMPK seem to be involved in regulation of insulin
      action. Although the picture is currently incomplete, it seems possible that AMPK
      or one of its effectors is a positive regulator of insulin-stimulated glucose
      transport. In addition to discussion of the latest literature regarding AMPK and
      insulin action, this review includes a non-technical summary for students,
      academics from other fields, interested professionals, and the general public.

PMID- 18049719
TI  - Epilepsy: being ill in more ways than one.
AB  - The majority of patients with epilepsy suffer from one or more psychiatric or
      somatic comorbid conditions, whose nature and prevalence vary with age and
      sociodemographic factors. In these patients, comorbid conditions have a major
      adverse effect on overall health and quality of life and substantially increase
      health care costs. Although there is an understanding of epidemiological aspects
      of the comorbidity of epilepsy, little is known about causal relationships,
      clinical interventions to prevent comorbidities, or the management of patients
      with multiple coexisting conditions. Both the effects of epilepsy therapies on
      comorbidities and the effects of comorbidities on the efficacy of epilepsy
      treatments warrant further study.

PMID- 18049720
TI  - ApoE, MemorE, and EpilepsE.

PMID- 18049721
TI  - Transcranial magnetic stimulation and sleep deprivation as experimental tools:
      when sleep deprivation is too exciting.

PMID- 18049722
TI  - Retigabine: has the orphan found a home?

PMID- 18049723
TI  - To treat or not to treat...Is it still the question?

PMID- 18049724
TI  - Hippocampal cell loss in posttraumatic human epilepsy.

PMID- 18049725
TI  - Animal modeling of poststroke seizures and epilepsy: 5-year update.
AB  - Poststroke seizures and epilepsy have been described in numerous clinical and
      epidemiological studies over many years. In contrast, the pathophysiological
      events occurring in injured brain that establish poststroke epileptogenesis and
      epilepsy are not known. However, in the last several years, animal modeling has
      made significant inroads toward an improved understanding of the progressive
      biochemical, anatomical, and physiological changes associated with both early and
      late seizures following stroke. A review of animal studies of poststroke seizures
      and epilepsy is presented.

PMID- 18049726
TI  - Does one neonatal seizure alter synaptic plasticity and cause lifelong cognitive
      impairment?

PMID- 18049727
TI  - Go "West," young man...The quest for animal models of infantile spasms (West
      syndrome).

PMID- 18049728
TI  - GABA excites and sculpts immature neurons well before delivery: modulation by
      GABA of the development of ventricular progenitor cells.

PMID- 18049730
TI  - Facile synthesis of hydrophobic fluoroalkyl functionalized silsesquioxane
      nanostructures.
AB  - New fluorinated polyhedral oligomeric silsesquioxane (F-POSS) structures
      possessing a high degree of hydrophobicity have been prepared via a facile corner
      capping methodology.

PMID- 18049729
TI  - Carboranyl thymidine analogues for neutron capture therapy.
AB  - Neutron capture therapy (NCT) is a binary radio-chemotherapeutic modality for the
      treatment of cancer. A major focus of NCT-related research is the development of
      novel tumor-selective agents that serve as the chemical component in NCT.
      Thymidine analogues substituted with a boron-containing carborane cluster at the
      N3 position, designated 3CTAs (3-carboranyl thymidine analogues), constitute one
      class of these new improved NCT agents. Their chemical, structural and biological
      properties are discussed in this Feature Article.

PMID- 18049731
TI  - Construction of a small-molecule-integrated semisynthetic split intein for in
      vivo protein ligation.
AB  - A new split intein-based protein ligation tool that is synthetically accessible
      and can be used for protein semisynthesis on the cell surface and potentially
      inside cells has been constructed.

PMID- 18049732
TI  - Low valent phosphorus in the molecular anions [P5Se12]5- and beta-[P6Se12]4-:
      phase change behavior and near infrared second harmonic generation.
AB  - The caesium salts of the novel molecular anions [P5Se12]5- and [P6Se12]4- are
      phase change materials and exhibit near infrared, non-linear optical second
      harmonic generation; [P5Se12]5- is a coordination complex with an octahedral P3+
      center chelated by two [P2Se6]4- ligands whereas [P6Se12]4- features a [P2]4+
      dimer chelated by two [P2Se6]4- ligands.

PMID- 18049733
TI  - Highly crystalline anisotropic superstructures via magnetic field induced
      nanoparticle assembly.
AB  - A magnetic field is successfully utilized to induce the fabrication of size
      controllable one-dimensional (1-D) supercrystals which are composed of a highly
      crystalline assembly of fcc-packed cobalt nanoparticles; the anisotropy
      associated supercrystal magnetism is enhanced with four times higher coercivity
      than that of randomly aggregated nanoparticles.

PMID- 18049734
TI  - Monodisperse water-soluble magnetite nanoparticles prepared by polyol process for
      high-performance magnetic resonance imaging.
AB  - A new class of monodisperse water-soluble magnetite nanoparticles was prepared by
      a simple and inexpensive method based on a polyol process, and their potential as
      MRI contrast agents was investigated.

PMID- 18049735
TI  - Syntheses and structures of mononuclear lutetium imido complexes with very short
      Lu-N bonds.
AB  - The reaction of 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-imine (ImDippNH) with
      trimethylsilylmethyllithium and anhydrous lutetium trichloride affords the imido
      complex [LuCl2(ImNDipp)(THF)3], which, on further reaction with dipotassium
      cyclooctatetraenide, K2(C8H8), leads to the half-sandwich cyclooctatetraenyl
      complex [(eta8-C8H8)Lu(ImNDipp)(THF)2]; both complexes contain very short Lu-N
      bond lengths, which are shorter than any previously reported Lu-N distances.

PMID- 18049736
TI  - Effective anion sensing based on the ability of copper to affect electron
      transport across self-assembled monolayers.
AB  - The ability of copper ions to affect the charge-transfer resistance of self
      assembled monolayers (SAMs) of a tris-(2-pyridylmethyl)amine-based ligand on to
      gold electrodes is used to create a novel, sensitive and selective
      electrochemical cyanide sensor.

PMID- 18049737
TI  - A hamburger-shaped helical stacking of disk-shaped ligands mediated by silver(II)
      ions.
AB  - We describe a hamburger-shaped helical structure of chiral and achiral C3
      symmetric disk-shaped ligands mediated by silver ions.

PMID- 18049738
TI  - Preferential separation of fullerene[84] from fullerene mixtures by
      encapsulation.
AB  - The encapsulation of fullerenes with a cyclotriveratrylene derivative, capable to
      self assemble into a dimer by means of three strong 4-ureidopyrimidinone
      quadruple hydrogen bonds is described. The system shows preference for C84,
      allowing its easy enrichment directly from fullerene mixtures.

PMID- 18049739
TI  - Electrochemical detection of kinase-catalyzed thiophosphorylation using gold
      nanoparticles.
AB  - An electrochemical biosensor for kinase-catalyzed reactions is coupled with the
      thiophosphorylation of the substrate peptide using adenosine 5'-[gamma-thio]
      triphosphate (ATP-S) as the co-substrate.

PMID- 18049740
TI  - A photocatalytic water splitting device for separate hydrogen and oxygen
      evolution.
AB  - A two-compartment Plexiglas cell has been set up and tested for separate hydrogen
      and oxygen production from photocatalytic water splitting on a thin TiO2 layer
      deposited by magnetron sputtering on a flat Ti electrode inserted between the two
      cell compartments.

PMID- 18049741
TI  - A diastereoselective carbocyclisation of allene-hydrazones through the
      intramolecular allylic transfer reaction.
AB  - A diastereoselective synthesis of cyclic hydrazines was achieved from a
      carbocyclisation of allene-hydrazones by the Pd-catalyzed distannylation of an
      allene moiety, followed by the transmetallation of allylic stannane intermediates
      with TiCl4.

PMID- 18049742
TI  - A multifunctional nanoassembly of mesogen-bearing amphiphiles and porphyrins for
      the simultaneous photodelivery of nitric oxide and singlet oxygen.
AB  - We report a molecular nanoassembly able to supply simultaneously, in the same
      region of space and under the exclusive control of visible light, nitric oxide
      and singlet oxygen, two species playing a key role in the therapy of cancer; the
      considerable fluorescence of this nanoaggregate and its reduced size (ca. 40 nm)
      represent additional advantages that make this photoactive vehicle an appealing
      candidate to be tested in biological systems.

PMID- 18049743
TI  - Entangled palladium nanoparticles in resin plugs.
AB  - Palladium nanoparticles were entrapped within resin plugs and used in a range of
      ligand-free cross-coupling reactions; the convenient modular format of the resin
      plug enhanced resin handling and allowed the catalysts to be easily recovered and
      multiply reused.

PMID- 18049744
TI  - Iridium catalysed synthesis of piperazines from diols.
AB  - A green and atom-economical method has been developed for the synthesis of
      piperazines by cyclocondensation of diols and amines in aqueous media in the
      presence of a catalytic amount of [Cp*IrCl2]2.

PMID- 18049745
TI  - Tetravalent cerium carbene complexes.
AB  - The tetravalent organometallic cerium complex [CeL4] is readily accessible from
      the oxidation of the trivalent [CeL3], L=a bidentate N-heterocyclic carbene
      alkoxide ligand, [C{(NPri)CHCHN}CH2CMe2O]. The [CeL4] complex should behave like
      the [UL4] analogue, but the two complexes show significantly different
      structures, highlighting the differences between 4f and 5f metals.

PMID- 18049746
TI  - The hydrothermal synthesis of tetragonal tungsten bronze-based catalysts for the
      selective oxidation of hydrocarbons.
AB  - Mixed metal oxides with tetragonal tungsten bronze (TTB) structure, showing high
      activity and selectivity for the gas phase partial oxidation of olefins, have
      been prepared by hydrothermal synthesis from Keggin-type heteropolyacids.

PMID- 18049747
TI  - Strong inhibition of cholera toxin binding by galactose dendrimers.
AB  - Galactose-containing dendrimers with long spacer arms inhibit cholera toxin
      binding as strongly as the natural ganglioside GM1 oligosaccharide does.

PMID- 18049748
TI  - Homoleptic Cu-phosphorus and Cu-ethene complexes.
AB  - Stable salts of the first homoleptic Cu-phosphorus and Cu-ethene complexes,
      [Cu(eta2-P4)2]+ and [Cu(eta2-C2H4)3]+, isolated by the aid of the weakly
      coordinating anion (WCA) [Al(OC(CF3)3)4]-, were obtained.

PMID- 18049749
TI  - Bismesitylmagnesium: a thermally stable and non-nucleophilic carbon-centred base
      reagent for the efficient preparation of silyl enol ethers.
AB  - Bismesitylmagnesium has been established as an accessible, practical, convenient,
      and non-nucleophilic carbon-centred base reagent for efficient access to silyl
      enol ethers from a series of ketone substrates at readily utilisable
      temperatures.

PMID- 18049750
TI  - Unique formation of two high-nuclearity metallamacrocycles from a mononuclear
      complex [Zn(dmpzdtc)2] (dmpzdtc=3,5-dimethylpyrazole-1-dithiocarboxylate) via CS2
      elimination.
AB  - Dissolution of a mononuclear complex [Zn(dmpzdtc)2] in BrCH2CH2Br or DMF
      saturated with water followed by CS2 elimination led to the formation of two
      unique high-nuclearity metallamacrocyclic complexes, [Zn4(micro-dmpz)6(micro
      OH)2]2 and [Zn4(micro-dmpz)6(micro-OH)2]4.

PMID- 18049751
TI  - Copper(I) mediated oligomerisation of a phosphaalkyne.
AB  - The oligomerisation of tert-butylphosphaalkyne, tBuC[triple bond, length as m
      dash]P, mediated by Cu(I) complexes yields an unprecedented C4P5 cage compound,
      which is stabilised in a matrix of copper(I) iodide.

PMID- 18049752
TI  - Bicyclic guanidine-catalyzed enantioselective phospha-Michael reaction: synthesis
      of chiral beta-aminophosphine oxides and beta-aminophosphines.
AB  - Chiral bicyclic guanidine has been found to catalyze the phospha-Michael
      reactions of diaryl phosphine oxide to nitroalkenes with high
      enantioselectivities, offering a direct methodology to prepare chiral beta
      aminophosphine oxides and beta-aminophosphines.

PMID- 18049753
TI  - Regioregular poly(3-hexyl)selenophene: a low band gap organic hole transporting
      polymer.
AB  - The synthesis of regioregular poly(3-hexyl)selenophene is reported, and its
      optical and electrical properties are compared to those of regioregular poly(3
      hexyl)thiophene.

PMID- 18049754
TI  - Asymmetric synthesis of (+)-cis-nemorensic acid from a chiral Diels-Alder adduct
      of 2,5-dimethylfuran.
AB  - (+)-cis-Nemorensic acid was synthesized from a chiral Diels-Alder adduct prepared
      by a catalytic enantioselective Diels-Alder reaction with 2,5-dimethylfuran and
      2,2,2-trifluoroethyl acrylate.

PMID- 18049755
TI  - Ionic strength mediated hydrophobic force switching of CF3-terminated ethylene
      glycol self-assembled monolayers (SAMs) on gold.
AB  - We have synthesised novel oligo(ethylene glycol), CF3-terminated switching self
      assembled monolayers, which allow the force experienced by a hydrophobic object
      to be controlled via the ionic strength of the environment.

PMID- 18049756
TI  - Ligand-free Pd/C-catalyzed Suzuki-Miyaura coupling reaction for the synthesis of
      heterobiaryl derivatives.
AB  - We have developed a mild and efficient protocol for the ligand-free and
      heterogeneous Pd/C-catalyzed hetero Suzuki-Miyaura coupling reaction that allows
      for the synthesis of both heteroaryl-aryl and heteroaryl-heteroaryl derivatives
      in good to excellent yields.

PMID- 18049757
TI  - Rapid intramolecular heterolytic dihydrogen activation by a four-membered
      heterocyclic phosphane-borane adduct.
AB  - A four-membered cyclic intramolecular phosphane-borane adduct activates
      dihydrogen to yield the respective ethylene-bridged zwitterionic phosphonium
      hydridoborate system, which reduces benzaldehyde.

PMID- 18049758
TI  - Liquid crystals carrying stereodefined vicinal difluoro- and trifluoro- alkyl
      motifs.
AB  - The synthesis of the stereospecifically fluorinated difluoro- and trifluoro- rac
      3 and rac-4 is described where the fluorine atoms are positioned adjacent/vicinal
      to each other and the physical characteristics of these candidate liquid crystals
      including negative dielectric anisotropy are measured and rationalised.

PMID- 18049759
TI  - Umbrella motion in aziridines: use of simple chemical inputs to reversibly
      control the rate of pyramidal inversion.
AB  - The molecular motion associated with atomic inversion at an aziridine nitrogen
      can be essentially halted by metal complexation; addition of a second chemical
      input that decomplexes the metal from the aziridine restores fast inversion (k=40
      s(-1) at 303 K).

PMID- 18049760
TI  - Ansa-tris(allyl) complexes of alkali metals: tripodal analogues of
      cyclopentadienyl and ansa-metallocene ligands.
AB  - Alkali metal complexes of two types of ansa-tris(allyl) ligand are reported; a
      monoanionic ansa-tris(allyl) ligand containing tin(II) is formally valence
      isoelectronic to the cyclopentadienyl ligand and a trianionic ansa-tris(allyl)
      ligand containing silicon(IV) is formally valence isoelectronic to an ansa
      metallocene ligand; the potential wider use of these tripodal ligands in
      coordination chemistry is discussed.

PMID- 18049761
TI  - Macropolyhedral boron-containing cluster chemistry. Novel intercluster linkages
      from the reaction of [Pt(cod)Cl2] and [PtMe2(PMe2Ph)2] with 6,6'-(B10H13)2O.
AB  - 6,6'-(B10H13)2O with [Pt(cod)Cl2] gives the [(B10H13OB10H11)Pt-{(B10H10OB10H12)]2
      anion in which, uniquely, the units are held together by a B-O-B linkage in
      combination with a B-B linkage; with [PtMe2(PMe2Ph)2] it gives [(PMe2Ph)2PtB10H10
      O,H-B10H11Pt(PMe2Ph)] in which, uniquely, the units are held together by an
      unsupported hydrogen-to-metal linkage as well as a B-O-B linkage.

PMID- 18049762
TI  - The unprecedented ring transformation from thiazoline-spiro-thiophene to
      thieno[2,3-b]pyrazine involved in the reaction of 2-thiocarbamoyl thiazolium
      salts with dimethyl acetylenedicarboxylate.
AB  - Reaction of 2-thiocarbamoyl thiazolium salts with dimethyl acetylenedicarboxylate
      proceeded via a tandem [3+2] cycloaddition and a unprecedented ring
      transformation to produce functionalized thieno[2,3-b]pyrazine derivatives in
      good to excellent yields.

PMID- 18049763
TI  - Removal of amorphous carbon for the efficient sidewall functionalisation of
      single-walled carbon nanotubes.
AB  - The sidewall functionalisation of carbon nanotubes using the standard nitric acid
      treatment can be greatly enhanced by first removing the amorphous carbon present
      in the sample.

PMID- 18049764
TI  - New water-soluble polyanionic dendrimers and binding to acetylcholine in water by
      means of contact ion-pairing interactions.
AB  - A new water-soluble polyanionic dendrimer containing 81 benzoate termini
      (diameter: 11+/-1 nm from DOSY NMR spectroscopy) has been synthesized; it
      interacts with acetylcholine cations in water-soluble assemblies in which each
      carboxylate terminus reversibly forms contact ion pairs and aggregates at the
      tether termini, as shown by 1H NMR spectroscopy.

PMID- 18049765
TI  - Synthesis of 5'-amino-5'-deoxyguanosine-5'-N-phosphoramidate and its enzymatic
      incorporation at the 5'-termini of RNA molecules.
AB  - 5'-amino-5'-deoxyguanosine-5'-N-phosphoramidate (GNHP) was synthesized in four
      steps from guanosine and was found to initiate T7 RNAP-promoted transcriptions to
      afford 5'-H2N-RNA that can be conjugated to activated esters.

PMID- 18049767
TI  - Understanding water quality trading: the basics.
AB  - The United States has entered a new era in water quality protection: the era of
      market-based incentives. In January 2003, the United States Environmental
      Protection Agency (EPA) issued its National Water Quality Trading Policy (Trading
      Policy) (USEPA, 2003). This action has generated greater interest in water
      quality trading and has prompted EPA to develop tools and training to assist
      interested parties in understanding what water quality trading is and what
      constitutes a successful trading program.

PMID- 18049768
TI  - Aquatic environmental nanoparticles.
AB  - Researchers are now discovering that naturally occurring environmental
      nanoparticles can play a key role in important chemical characteristics and the
      overall quality of natural and engineered waters. The detection of nanoparticles
      in virtually all water domains, including the oceans, surface waters,
      groundwater, atmospheric water, and even treated drinking water, demonstrates a
      distribution near ubiquity. Moreover, aquatic nanoparticles have the ability to
      influence environmental and engineered water chemistry and processes in a much
      different way than similar materials of larger sizes. This review covers recent
      advances made in identifying nanoparticles within water from a variety of
      sources, and advances in understanding their very interesting properties and
      reactivity that affect the chemical characteristics and behaviour of water. In
      the future, this science will be important in our vital, continuing efforts in
      water safety, treatment, and remediation.

PMID- 18049769
TI  - Application of flow cytometry and cell sorting to the bacterial analysis of
      environmental aerosol samples.
AB  - Flow cytometry (FCM) combined with viability staining is a useful tool in
      discerning viable bacteria in environmental samples where traditional culture
      methods may fail. Contamination of aerosol samples with dust and other non
      biological particles can interfere with accurate sample analysis and therefore
      there is a desire to exclude those particles from analysis. Particles were sorted
      according to their light scattering properties, cultured and isolates obtained.
      Isolates were cultured in suspension and reanalyzed by flow cytometry. The
      isolates were also analyzed and identified by DNA sequence analysis. Isolates
      with statistically similar light scattering properties shared common sequence
      identification. Isolates exhibited distinct light scattering profiles that
      roughly correlated with their originating gate, but often the peak of the profile
      was outside that gate.

PMID- 18049770
TI  - A novel biomonitoring system using microbial fuel cells.
AB  - A novel biomonitoring system using microbial fuel cells for detecting the inflow
      of toxic substances into water systems has been developed for the purpose of on
      site and on-line monitoring. The characteristics of electric current generation
      by electrochemically-active bacteria were conveniently monitored using a
      microbial fuel cell format and a computer-controlled potentiometer. When toxic
      substances (an organophosphorus compound, Pb, Hg, and PCBs) were added to the
      microbial fuel cell, rapid decreases in the current were observed. The inhibition
      ratios caused by inflow of these toxic substances (1 mg l(-1)) were 61%, 46%, 28%
      and 38%, respectively, when compared to the control, and generally increased in
      proportion to the addition time and concentration of toxic substances. When real
      wastewater was applied from a local wastewater treatment plant, more significant
      current decreases and higher inhibition ratios were observed following the
      introduction of toxic substances than in the laboratory tests. For example, the
      inhibition ratio was 76% on addition of a 1 mg l(-1) Cd and 1 mg l(-1) Pb
      mixture. Application of the microbial fuel cell for pollutant biomonitoring is
      discussed.

PMID- 18049771
TI  - Determination of organophosphorus fire retardants and plasticizers in wastewater
      samples using MAE-SPME with GC-ICPMS and GC-TOFMS detection.
AB  - Determination of organophosphorus fire retardants and plasticizers at trace
      levels in wastewater is described. In this work, microwave assisted extraction
      (MAE) and solid-phase microextraction (SPME) are used for sample preparation to
      extract and preconcentrate the analytes, followed by analysis by gas
      chromatography coupled to inductively coupled plasma mass spectrometry (GC-ICP
      MS) for phosphorus-specific detection. Gas chromatography coupled to time of
      flight mass spectrometry (GC-TOF-MS) was used to confirm the organphosphorus fire
      retardants in wastewater. The detection limits of organophosphorus fire
      retardants (OPFRs) were 29 ng L(-1) for tri-n-butyl phosphate (TnBP), 45 ng for
      L(-1) for tris(2-butoxyethyl)phosphate (TBEP), and 50 ng L(-1) for tris(2
      ethylhexyl)phosphate (TEHP). Optimized extraction conditions were performed at 65
      degrees C for 30 min and with 10% NaCl. Application of MAE during the sample
      preparation prior to the SPME allowed the detection of tris(2-ethylhexyl)
      phosphate, which has been difficult to determine in previous work. Application of
      the method to wastewater samples resulted in detecting 3.1 microg L(-1) P from
      TnBP, 5.0 microg L(-1) P from TBEP, and 4.0 microg L(-1) P from TEHP. The
      presence of these compounds were also confirmed by SPME-GC-TOF-MS.

PMID- 18049772
TI  - Monitoring terbutryn pollution in small rivers of Hesse, Germany.
AB  - Four small river systems in Hesse, Germany, were investigated with respect to
      seasonal and spatial concentrations of the herbicide terbutryn [2-(t-butylamino)
      4-(ethylamino)-6-(methylthio)-s-triazine]. Despite introduction of a ban on its
      use as a herbicide in July 2003, terbutryn was still present in the rivers during
      the whole sampling period from September 2003 to September 2006, and there was no
      trend of decreasing concentration during this time. In the Weschnitz and Modau
      river systems the mean terbutryn concentration exceeded the German drinking water
      ordinance threshold value for single biocides. Maximum concentrations of up to
      5.6 microg l(-1) were determined in the Weschnitz River. Higher terbutryn
      concentrations in summer are suggested to originate from agricultural sources, as
      well as from sediment redissolution. Effluents of two sewage treatment plants had
      high terbutryn concentrations, indicating that terbutryn enters the rivers from
      this source. Sources other than agriculture must explain terbutryn occurrence in
      the rivers during winter, when farm pesticide application typically ceases. The
      potential for mobilization of terbutryn from sediments and leaching from soils
      are discussed.

PMID- 18049773
TI  - Catalytic hydrogenation of polyaromatic hydrocarbon (PAH) compounds in
      supercritical carbon dioxide over supported palladium.
AB  - A series of supported palladium catalysts were evaluated for their ability to
      mediate the complete hydrogenation of polycyclic aromatic hydrocarbon (PAH)
      compounds. Benzo[a]pyrene (B[a]P) or phenanthrene (Phe) in hexane was merged with
      a hydrogen-carbon dioxide [5% (w/w) H(2)/CO(2)] stream and transferred to a flow
      through mini-reactor (capacity ca. 1 g) that was maintained at 90 degrees C under
      a back-pressure of 20.68 MPa. Effluent from the reactor trapped in hexane was
      monitored/quantified by gas chromatography-mass spectrometry. Catalyst
      formulations supported on iron powder, high density polyethylene (HDPE) or gamma
      alumina were prepared and compared in terms of hydrogenation activity as measured
      by the quantity of substrate per unit time that could be perhydrogenated to
      toxicologically innocuous products. Both of the Pd preparations supported on
      gamma-alumina were more efficient than a commercial Pd(0) (5% w/w) on gamma
      Al(2)O(3) formulation or preparations supported on HDPE or the iron powder.
      Bimetallic mixtures with Pd increased the hydrogenation activity when co
      deposited with Cu or Ni but not with Ag or Co. However, increases in
      hydrogenation activity by increasing the loading of Pd (or bimetallic mixture) on
      this surface were limited. Despite using supercritical carbon dioxide (scCO(2))
      to swell the surfaces of the polymer, the deposition of nanoparticles within the
      polyethylene formulation was appreciably less active than either the oxidic or
      the Fe(0) formulations.

PMID- 18049774
TI  - Performance of an electrochemical COD (chemical oxygen demand) sensor with an
      electrode-surface grinding unit.
AB  - An electrochemical COD (chemical oxygen demand) sensor using an electrode-surface
      grinding unit was investigated. The electrolyzing (oxidizing) action of copper on
      an organic species was used as the basis of the COD measuring sensor. Using a
      simple three-electrode cell and a surface grinding unit, the organic species is
      activated by the catalytic action of copper and oxidized at a working electrode,
      poised at a positive potential. When synthetic wastewater was fed into the
      system, the measured Coulombic yields were found to be dependent on the COD of
      the synthetic wastewater. A linear correlation between the Coulombic yields and
      the COD of the synthetic wastewater was established (10-1000 mg L(-1)) when the
      electrode-surface grinding procedure was activated briefly at 8 h intervals. When
      various kinds of wastewater samples obtained from various sewage treatment plants
      were measured, linear correlations (r(2)> or = 0.92) between the measured EOD
      (electrochemical oxygen demand) value and COD of the samples were observed. At a
      practical wastewater treatment plant, the measurement system was successfully
      operated with high accuracy and good stability over 3 months. These experimental
      results show that the application of the measurement system would be a rapid and
      practical method for the determination of COD in water industries.

PMID- 18049775
TI  - Reproducibility and imputation of air toxics data.
AB  - Ambient air quality datasets include missing data, values below method detection
      limits and outliers, and the precision and accuracy of the measurements
      themselves are often unknown. At the same time, many analyses require continuous
      data sequences and assume that measurements are error-free. While a variety of
      data imputation and cleaning techniques are available, the evaluation of such
      techniques remains limited. This study evaluates the performance of these
      techniques for ambient air toxics measurements, a particularly challenging
      application, and includes the analysis of intra- and inter-laboratory precision.
      The analysis uses an unusually complete-dataset, consisting of daily measurements
      of over 70 species of carbonyls and volatile organic compounds (VOCs) collected
      over a one year period in Dearborn, Michigan, including 122 pairs of replicates.
      Analysis was restricted to compounds found above detection limits in > or =20% of
      the samples. Outliers were detected using the Gumbell extreme value distribution.
      Error models for inter- and intra-laboratory reproducibility were derived from
      replicate samples. Imputation variables were selected using a generalized
      additive model, and the performance of two techniques, multiple imputation and
      optimal linear estimation, was evaluated for three missingness patterns. Many
      species were rarely detected or had very poor reproducibility. Error models
      developed for seven carbonyls showed median intra- and inter-laboratory errors of
      22% and 25%, respectively. Better reproducibility was seen for the 16 VOCs
      meeting detection and reproducibility criteria. Imputation performance depended
      on the compound and missingness pattern. Data missing at random could be
      adequately imputed, but imputations for row-wise deletions, the most common type
      of missingness pattern encountered, were not informative. The analysis shows that
      air toxics data require significant efforts to identify and mitigate errors,
      outliers and missing observations, and that these steps are essential and should
      be performed prior to using these data in receptor, exposure, health and other
      applications.

PMID- 18049776
TI  - Adsorption of domoic acid to marine sediments and clays.
AB  - Conditional solid-water distribution coefficients (K(d)) for the adsorption of
      domoic acid (DA) to a series of complex sediments and clays were determined in
      artificial seawater. K(d) ranged from 5.11 L g(-1) to 0.97 L g(-1), with a
      corresponding ranking of: kaolinite > Gulf of Mexico sediment > Santa Barbara
      Basin sediment > Bread and Butter Creek sediment > poorly crystallized kaolin >
      Ca-montmorillonite > Na-montmorillonite > well crystallized kaolin > diatomaceous
      earth. Adsorption correlated with the anion exchange capacity of the clays tested
      (R(2) = 0.98), but not the more structurally complex sediments. The effect of
      added transition metals (Fe(iii), Cu(ii), Al(iii)) and terrestrially derived
      dissolved organic matter (Suwannee River DOM, SRDOM) on DA adsorption to Na
      montmorillonite, well crystallized kaolin, and Gulf of Mexico sediment, was also
      tested. The addition of transition metals led to increased adsorption to all
      surfaces by a factor of 2-7, presumably by enabling the adsorption of DA-metal
      complexes. SRDOM enhanced DA adsorption by a factor of approximately 2.5. The
      release of adsorbed DA from sediments was also examined. Under our conditions,
      adsorbed DA equilibrated with the overlying aqueous phase within minutes with
      approximately 50% release.

PMID- 18049777
TI  - Effects of marine biofouling on gas sensor membrane materials.
AB  - The use of underwater gaseous sensors has increased rapidly in the last 10 years.
      The majority of such sensors employ a thin membrane through which the gas
      diffuses. These sensors are potentiometric gas-sensing probes and essentially
      they are ion-selective electrodes. The deployment time of these membranes is
      curtailed by the formation of biofouling on the membrane leading to erroneous
      results. The physical properties of a variety of commonly used membranes were
      investigated using SEM and AFM. This showed that there were differences in
      topography between the PTFE membranes, such as pore sizes and surface roughness,
      which may be attributed to the manner in which they are manufactured. The pore
      size of the PTFE membranes varied greatly, ranging from circular pores with a
      diameter of 500 nm to elongated pores measuring 1 x 22 microm. The contact angle
      of each membrane showed that they were all hydrophobic. The amount of fouling on
      each was also observed and its affect on oxygen diffusion was monitored. Fouling
      slowed down the response of the instrument and caused reduced diffusion through
      the membranes. The amount of fouling varied between the membranes with the YSI
      membrane fouling least. Some of the membranes tested did foul less than others
      and there could be lifetime advantages of choosing a membrane with a smoother
      surface and a small pore size.

PMID- 18049778
TI  - Investigation of 15-year-old municipal solid waste deposit profiles by means of
      FTIR spectroscopy and thermal analysis.
AB  - Five profiles of a 15-year-old bank containing over three weeks composted
      municipal solid waste were characterized by means of different parameters
      habitually applied in waste management (loss on ignition, total organic carbon,
      total nitrogen, NH(4)-N, pH), and in addition by humic acid determination, FTIR
      spectroscopy and thermal analysis. Stabilization processes are revealed by humic
      acid contents. Over the 15 year period organic matter had developed in various
      ways. Highest humic acid contents were found at 0.5 m below the surface. Below
      1.0-1.5 m anaerobic conditions dominated causing a strong decline of humic acid
      concentrations. Despite similar contents of organic matter at 0.5 m and at 3.0 m
      organic matter quality differed. These differences were verified by infrared
      spectroscopic investigations and thermal analyses (differential scanning
      calorimetry DSC). The spectral pattern of 15-year-old profile samples (municipal
      solid waste including the biogenic fraction) was compared to current municipal
      solid waste and abandoned landfill materials. Current municipal solid waste
      samples comprised different degradation stages from fresh materials to stabilized
      waste, suitable for landfilling according to Austrian standards. Municipal solid
      waste originating from abandoned landfills closed in the seventies represented
      stable material. Principal component analysis was performed to detect
      similarities and differences. It is evident that the profile samples constitute a
      particular group in between municipal solid waste and abandoned landfill
      material. Some differences can be attributed to the divergent composition of
      municipal solid waste in the eighties when the organic fraction was not
      separated. Otherwise, landfill materials from the seventies with the same
      composition regarding the organic fraction were deposited together with
      construction waste. Heat flow curves (DSC profiles) of municipal solid waste,
      representing different decomposition stages, illustrate the development of
      enthalpies and reveal the status of the profile samples. It is evident that
      mechanical-biological pretreatment leads to a faster stabilization of waste
      organic matter.

PMID- 18049779
TI  - Clear and present danger? The use of a yeast biosensor to monitor changes in the
      toxicity of industrial effluents subjected to oxidative colour removal
      treatments.
AB  - Discharges of coloured effluents into surface waters provide conspicuous evidence
      of the impact of industry on the environment. The textile industry is an obvious
      candidate for sources of such discharges. Conventional treatment methods appear
      to alleviate this situation by removing colour, however the affect on toxicity is
      less obvious. The objective of this study was to examine the changes in effluent
      toxicity during the course of two alternative wastewater treatment methods,
      ozonation and electrochemical oxidation, using a novel toxicity biosensor,
      GreenScreen EM. The biosensor is capable of measuring both general acute toxicity
      (cytotoxicity), and more specifically genotoxicity, that is damage to a cell's
      DNA structure, replication or distribution, caused by substances that may be
      mutagenic and/or carcinogenic. The biosensor utilises a modified strain of the
      brewers yeast Saccharomyces cerevisiae, incorporating a gene encoding green
      fluorescent protein (GFP) linked to the inducible promoter of the DNA damage
      responsive RAD54 gene. Upon exposure to a genotoxin, the production of GFP is up
      regulated in parallel with RAD54, and the resulting cellular fluorescence
      provides a measure of genotoxicity. Acute toxicity is simultaneously determined
      by monitoring relative total growth of the cell culture during incubation. The
      results presented in this paper show that a reduction in colouration does not
      necessarily correspond to a reduction in effluent toxicity.

PMID- 18049780
TI  - Gaseous and particulate polycyclic aromatic hydrocarbons (PAHs) emissions from
      commercial restaurants in Hong Kong.
AB  - Commercial cooking emissions are important air pollution sources in a heavily
      urbanized city. Exhaust samples were collected in six representative commercial
      kitchens including Chinese restaurants, Western restaurants, and Western fast
      food restaurants in Hong Kong during peak lunch hours. Both gaseous and
      particulate emissions were evaluated. Eight gaseous and twenty-two particulate
      polycyclic aromatic hydrocarbons (PAHs) were quantified in this study. In the
      gaseous phase, naphthalene (67-89%) was the most abundant PAH in all of the
      exhaust samples. The contribution of acenaphthylene in the gaseous phase was
      significantly higher in emissions from the Chinese restaurants, whereas fluorene
      was higher in emissions from the Western cooking style restaurants (i.e., Western
      restaurants and Western fast-food restaurants). Pyrene is the most abundant
      particulate PAH in the Chinese restaurants (14-49%) while its contribution was
      much lower in the Western cooking style restaurants (10-22%). Controlled cooking
      conditions were monitored in a staff canteen to compare the emissions from
      several different local cooking styles, including deep frying, steaming, and
      mixed cooking styles (combination of steaming and frying). Deep frying produced
      the highest amount of total gaseous PAHs, 6 times higher than the steaming.
      However, steaming produced the highest particulate emissions. The estimated
      annual gaseous PAH emissions for the Chinese restaurants, Western restaurants,
      and Western fast-food restaurants were 255, 173, and 20.2 t y(-1) whereas 252,
      1.9, and 0.4 t y(-1) were estimated for particulate phase PAH emissions. The
      study provides useful information and estimates for PAH emissions from commercial
      cooking exhaust in Hong Kong.

PMID- 18049781
TI  - Source to sink tracking of selected human pharmaceuticals from two Oslo city
      hospitals and a wastewater treatment works.
AB  - The occurrence of twenty pharmaceutical compounds was quantitatively determined
      in effluents from two major Oslo city hospitals, Rikshospitalet and Ulleval,
      along with influent, sludge and final effluent from the city's VEAS wastewater
      treatment works (WTW). Composite hospital effluents were collected over a twelve
      week period and were showed to contain paracetamol, metoprolol, diclofenac,
      ibuprofen, 17beta-Estradiol, estriol, estrone, oxytetracycline, tetracycline,
      doxycycline, chlorotetracycline, demeclocycline, trimethoprim, ciprofloxacin,
      sulfamethoxazole, cyclophosphamide and ifosfamide. Three pharmaceuticals were not
      detected above the limit of detection; cefuroxime, 17alpha-ethinylestradiol and
      meclocycline. Composite influent, sludge and effluent samples were collected from
      VEAS WTW over a seven week period. The influent into VEAS WTW contained all of
      the same selected substances detected in the hospital effluents, except for
      oxytetracycline, chlorotetracycline, demeclocycline, cyclophosphamide and
      ifosfamide. The percentage of pharmaceuticals entering the works from the
      hospitals was <10% for all of the selected compounds. VEAS sludge samples
      contained a different profile of substances reflecting their physico-chemical
      properties. Hydrophobic antibiotics, such as oxytetracycline, tetracycline and
      ciprofloxacin, were detected in all of the collected sludge samples. Their
      absence in the collected influent samples suggests that they enter the works
      bound to effluent particles, with the dissolved fraction observed in the hospital
      effluents partitioning onto particulate matter within the sewerage network. The
      final effluent from VEAS WTW contained reduced concentrations of many
      pharmaceuticals, including paracetamol, ibuprofen and sulfamethoxazole. For other
      compounds, such as metoprolol, diclofenac and trimethoprim, there were often
      higher concentrations in the effluent than the influent. These effluent
      concentrations represent median inputs varying from low g day(-1) (e.g.
      paracetamol and ibuprofen) to nearly 200 g day(-1) (e.g. metoprolol and
      trimethoprim) into Oslofjord. A simple risk assessment showed that the antibiotic
      ciprofloxacin may at times pose an acute risk to the Oslofjord aquatic
      environment.

PMID- 18049782
TI  - Phthalate levels in Norwegian indoor air related to particle size fraction.
AB  - Phthalates are found in numerous consumer products, including interior materials
      like polyvinyl chloride (PVC). Several studies have identified phthalates in
      indoor air. A recent case-control study demonstrated associations between
      allergic symptoms in children and the concentration of phthalates in dust
      collected from their homes. Here we have analyzed the content of selected
      phthalates in particulate matter (PM): PM(10) and PM(2.5) filter samples
      collected in 14 different indoor environments. The results showed the presence of
      the phthalates di-n-butyl phthalate (DBP), butyl benzyl phthalate (BBP),
      dicyclohexyl phthalate (DCHP) and diethyl hexyl phthalate (DEHP) in the samples.
      The dominating phthalate in both PM(10) and PM(2.5) samples from all locations
      was DBP. More than a 10-fold variation in the mean concentration of total
      phthalates between sampling sites was observed. The highest levels of total
      phthalates were detected in one children's room, one kindergarten, in two primary
      schools, and in a computer room. The relative contribution of total phthalates in
      PM(10) and PM(2.5) was 1.1 +/- 0.3% for both size fractions. The contribution of
      total phthalates in PM(2.5) to total phthalates in PM(10) ranged from 23-81%,
      suggesting different sources. Of the phthalates that were analyzed in the PM
      material, DBP was found to be the major phthalate in rubber from car tyres.
      However, our analyses indicate that tyre wear was of minor importance for indoor
      levels of both DBP as well as total phthalates. Overall, these results support
      the notion that inhalation of indoor PM contributes to the total phthalate
      exposure.

PMID- 18049783
TI  - Interpretation of standard leaching test BS EN 12457-2: is your sample hazardous
      or inert?
AB  - A slag sample from a lead refiner has been obtained and given to two analytical
      laboratories to determine the release of trace elements from the sample according
      to BS EN 12457-2. Samples analysed by one laboratory passed waste acceptance
      criteria, leading it to be classified as an inert material; samples of the same
      material analysed by the other laboratory failed waste acceptance criteria and
      were classified as hazardous. It was found that the sample preparation procedure
      is the critical step in the leaching analysis and that the effects of particle
      size on leachability should be taken into account when using this standard. The
      purpose of this paper is to open a debate on designing a better defined standard
      leaching test and making current waste acceptance criteria more flexible.

PMID- 18049785
TI  - [2007 Nobel Prize in medicine. Knock-out mice revolutionize genetics].

PMID- 18049786
TI  - Polybrominated diphenyl ethers and polybrominated biphenyls in sediment and
      floodplain soils of the Saginaw River watershed, Michigan, USA.
AB  - Despite known historical release of polybrominated biphenyls (PBBs; brominated
      flame retardants) into the Pine River (St. Louis, MI, USA), a tributary of the
      Tittabawassee River which subsequently forms the Saginaw River and flows into
      Saginaw Bay-Lake Huron, little is known about spatial patterns of sediment
      contamination by PBBs in this watershed. In this study, concentrations of two
      groups of brominated flame retardants, polybrominated diphenyl ethers (summation
      PBDE; BDE-28, -47, -66, -100, -99, -85, -154, -153, -138, and -209) and PBBs were
      measured in more than 120 floodplain soil samples, surface sediment samples, and
      sediment cores collected in 2004 from the Shiawassee River, the Saginaw River,
      and Saginaw Bay, Michigan. In addition, sediment samples collected in 2002 from
      the Pine River and the Tittabawassee River were analyzed, to elucidate riverine
      transport and attenuation of PBBs and PBDEs in this watershed. The mean
      concentration of summation PBDE decreased from upstream to downstream, from the
      Shiawassee River and the Tittabawassee River to Saginaw Bay. BDE-209 was the
      predominant congener, accounting for 79% of the total PBDE concentration in the
      Shiawassee River and 90% in the Saginaw River. BDE-209 was followed, in order of
      decreasing abundance, by BDE-47, -99, and -100. The proportions of BDE congeners
      varied by water body, and by sample type, whether floodplain soil or sediment.
      High summation PBDE concentrations were found in floodplain soil collected from
      the Shiawassee River near Chase Lake (55 ng/g, dry weight) and in sediment from
      the Saginaw River near Middleground Island (49 ng/g, dry weight). There was a
      significant positive correlation between summation (9)PBDE (tri- to hexa-BDE) and
      BDE-209 in samples collected from the Shiawassee River and Saginaw Bay, but not
      in samples from the Saginaw River. Among PBBs, bromobiphenyl congener 153 (BB
      153) was found in sediments from the Saginaw River but not in sediments from the
      Shiawassee River. An elevated concentration of BB-153 (13.5 ng/g, dry weight) was
      found in floodplain soil collected from the Pine River. The BB-153 concentration
      in sediment decreased by two to three orders of magnitude, from the Pine River
      downstream to Saginaw Bay. An elevated concentration of BB-153 (4.7 ng/g) was
      found in sediment collected from the mouth of the Saginaw River. Surface
      sediments collected near the mouth of the Saginaw River contained higher
      concentrations of both PBDEs and PBBs than did the subsurface sediments at these
      locations.

PMID- 18049787
TI  - Overlapping covered stents to exclude a postcoarctation stenting aortic aneurysm.
AB  - An 18-year-old boy who underwent coil occlusion of a patent ductus arteriosus and
      stenting for aortic coarctation at 13 years of age had evidence of re-stenosis.
      Cardiac catheterization and angiography showed a 25-mmHg gradient across the
      stent and a large aneurysm originating at midstent level. The aneurysm measured 2
      cm in width and 4.3 cm in length. At a subsequent catheterization procedure, two
      4.5-cm-long overlapping Cheatham platinum covered stents were implanted,
      completely excluding the aneurysm. Computed tomographic (CT) angiography 2 years
      later showed no evidence of endoleak or re-stenosis.

PMID- 18049788
TI  - When the third degree is necessary: do pediatricians obtain enough information to
      detect patients at risk for HCM?
AB  - This study was designed to see if pediatricians are collecting sufficient data in
      family histories to be able to ascertain whether children are at risk for
      hypertrophic cardiomyopathy (HCM). Surveys were returned by 326 general
      pediatricians who were members of the Second Chapter of the American Academy of
      Pediatrics. The majority of pediatricians (98.2%) reported taking family
      histories; however, only 51.2% reported that this information was updated on a
      regular basis. Only 29.8% of the pediatricians reported including all five risk
      factors for HCM in a medical family history. Although almost all of the
      pediatricians reported including first-degree relatives in medical family
      histories, only 40.5% reported including all second-degree relatives. Female
      physicians were found to take more thorough medical family histories than male
      physicians, and foreign medical school graduates were found to take more thorough
      medical family histories than US medical school graduates. Additionally,
      graduates of foreign medical schools reported updating medical family histories
      more often than graduates of US medical schools. This study suggests that
      pediatricians might not be identifying risks pertinent to the identification of
      HCM.

PMID- 18049789
TI  - Relationship of inferior gluteal nerves and vessels: target for application of
      stimulation devices for the prevention of pressure ulcers in spinal cord injury.
AB  - A study was carried out to determine whether the location of the inferior gluteal
      nerve could be reliably predicted using external anatomy or vascular imaging.
      This study was motivated by our group's development of an electrical stimulation
      system to provide direct gluteal stimulation in paralyzed individuals, in
      particular those with spinal cord injury (SCI). Pressure ulcers are a common
      complication for many individuals with reduced mobility. Numerous approaches have
      been employed to treat and prevent pressure ulcers; however no procedure or
      nursing care regimen has been successful in eradicating them completely. Our
      group seeks to prevent skin breakdown in susceptible patients by direct
      electrical stimulation of the paralyzed gluteal muscle, leading to improved
      circulation and increased muscle mass (hypertrophy) in the treated area.
      Currently, percutaneous electrodes are placed through an extensive probing
      process to select the motor point of the target muscle. We examined 15 cadaver
      gluteal regions to identify the relationship between the internal anatomy of the
      inferior gluteal artery and nerve as well as the relationship to external
      anatomic landmarks. The cadavers displayed variability with regard to the
      morphology of the branches of both nerve and artery. Furthermore, there did not
      appear to be any relationship between the relative positions of the nerve and
      artery. However, the potential target area of the proximal origin of the inferior
      gluteal nerve could reliably be predicted from the external bony anatomy of the
      lower pelvis.

PMID- 18049790
TI  - Radiographic and microscopic anatomy of the mid-palatal suture in the elderly.
AB  - In a previous radiological study of the mid-palatal suture, it has been
      demonstrated that its obliteration was occurring during adult life and varied. In
      order to determine the histological status of mid-palatal suture in elderly men,
      20 human palates aged more than 70 were examined by occlusal radiographs and
      histological study of the suture. In all palates the suture was ossified in the
      anterior thirds and made of conjunctive tissue in the posterior third. This
      particular evolution could be correlated to the mastication forces acting on the
      maxillary bones during the entire life.

PMID- 18049791
TI  - Does the maxillary division of the trigeminal nerve traverse the cavernous sinus?
      An anatomical study and review of the literature.
AB  - AIM: Many authors have included the V2 segment of the trigeminal nerve as a
      component of the cavernous sinus. However, many authorities have stated that this
      part of the fifth cranial nerve is not within this intracranial venous sinus.
      MATERIALS AND METHODS: To further elucidate this potentially important
      relationship, 10 fresh cadaveric heads underwent injection of the cavernous sinus
      with blue latex or a cresyl-violet solution. Subsequent sectioning in the coronal
      plane in 1 cm sections from the level of the trigeminal ganglia anteriorly to the
      level of the superior orbital fissure was made. Observations were then made
      between the relationships of the cavernous sinus and the V2 nerve. RESULTS: On
      all 20 sides, the V2 segment of the trigeminal nerve did not have filling of
      latex or cresyl-violet mixture lateral to it thus implying that this part of the
      trigeminal nerve is not found within the cavernous sinus. Two sides did
      demonstrate an emissary vein that traveled with the V2 part of the trigeminal
      nerve through the foramen rotundum toward the cavernous sinus. CONCLUSIONS: Based
      on our findings, the V2 part of the trigeminal nerve is not found bathed with
      venous blood within the cavernous sinus. Reports that state the contrary may have
      confused laterally positioned emissary veins as being part of the cavernous sinus
      and therefore erroneously concluded that V2 was within this cranial venous sinus.
      These data may prove useful to neurosurgeons that operate in the region of the
      cavernous sinus or to radiologists who interpret imaging of this area.

PMID- 18049792
TI  - Occurrence of genetic bottlenecks during citrus tristeza virus acquisition by
      Toxoptera citricida under field conditions.
AB  - In this study, we address the involvement of T. citricida in strain segregation
      and genetic bottleneck events by comparing the nucleotide diversity of CTV coat
      protein (CP) gene variants present in field-grown trees with that of variants
      retrieved from single apterous aphids. Plant material and aphids were collected
      in orange orchards in the northern part of Portugal. Shoots from two trees that
      were found to be positive using ELISA and twenty-four apterous aphids from these
      same trees were selected for individual molecular assays. CTV was detected in 60%
      of the aphids by amplification of a 417-bp fragment of the CP gene. Analysis of
      molecular variance (AMOVA) of this fragment revealed that most of the variation
      of the virus was found among individual aphids (FSC: 0.766) within each location.
      Nucleotide diversity comparison between the pool of sequences obtained from a
      given shoot and sequences obtained from individual aphids present on that shoot
      showed a reduction of more than one order of magnitude in most cases. Computer
      simulations of random virus acquisition by single aphids showed that in 54% of
      the cases only a single CP gene phylogenetic group was acquired. However, a small
      number of aphids (e.g. 6) was enough to acquire the full complement of
      phylogenetic groups present.

PMID- 18049793
TI  - Lack of association of single nucleotide polymorphism in LRCH1 with knee
      osteoarthritis susceptibility.
AB  - A genetic association of knee osteoarthritis (OA) and a C/T transition single
      nucleotide polymorphism (SNP) (rs912428) located in intron 1 of the LRCH1 gene
      has recently been reported in European Caucasians; however, the results are
      inconsistent. Our objective was to evaluate the association in different knee OA
      populations. Three case-control association studies were conducted in Han
      Chinese, Japanese, and Greek Caucasian populations. The LRCH1 SNP was genotyped
      in patients who had primary symptomatic knee OA with radiographic confirmation
      and in matched controls, and the association was examined. We performed a meta
      analysis for the studies together with results of two previous papers using the
      DerSimonian-Laird procedure and calculated the power of the pooled studies by the
      software R. A total of 1,145 OA patients and 1,266 controls were genotyped. No
      significant difference was detected in genotype or allele frequencies between
      knee OA and control groups in the three populations (all P > 0.05). Association
      was not observed even after stratification by gender and Kellgren/Lawrence (K/L)
      scores. Meta-analysis also supported the lack of association between LRCH1 and
      knee OA. The strong heterogeneity between original and replication studies was
      detected in Caucasian populations. However, a tendency for the increase of TT
      genotype was observed in the European populations (OR = 1.46, P = 0.06). The
      powers for European and Asian replication studies were less than 0.8. Our results
      suggest that there is no association between LRCH1 and knee OA. However, lack of
      association should be concluded by further replication studies.

PMID- 18049794
TI  - Submucosal glycerol injection-assisted laser surgical treatment of oral lesions.
AB  - Recently, we modified laser surgery for superficial lesions in the oral cavity by
      using submucosal glycerol injection. This procedure was based on a technique for
      endoscopic mucosal resection (EMR) in the gastrointestinal tract. The aim of this
      study was to evaluate the effectiveness of the modified laser surgery assisted by
      a submucosal glycerol injection. Eleven superficial oral lesions in ten patients
      were treated with diode laser (continuous wave mode, 3 W) after a submucosal
      injection of glycerol solution. Injection of glycerol solution created mucosal
      expansion, which enabled the procedures to be done without bleeding, over
      cutting, over coagulation and unintended irradiation. The surface of the wounds
      showed little carbonization, resulting in good healing. Submucosal glycerol
      injection for laser treatment in the oral cavity is a promising technique for
      treating superficial oral lesions by virtue of less invasion and good results.

PMID- 18049795
TI  - Comparison of the effects of pretreatment with tirofiban, clopidogrel or both on
      the inhibition of platelet aggregation and activation in patients with acute
      coronary syndromes.
AB  - OBJECTIVE: We sought to compare platelet inhibition produced by three
      antiplatelet regimens. METHODS AND RESULTS: Sixty NSTE-ACS patients undergoing
      coronary angiography treated with aspirin and enoxaparin were randomised to
      receive tirofiban 0.4 microg/kg/min over 30 min plus 0.15 microg/kg/min over 24 h
      (A), clopidogrel 600 mg (B), clopidogrel 300 mg plus tirofiban (C); blood samples
      were taken at baseline and 2, 6 and 24 h after the drug administration, and were
      analyzed by light transmission aggregometry and flow cytometry. Treatment with
      clopidogrel 600 mg significantly reduced P-selectin expression in comparison with
      tirofiban alone at all time points (group B vs. A: P < 0.0001). However tirofiban
      inhibited platelet aggregation significantly more than clopidogrel 600 mg during
      the first 6 h (group A vs. B: P < 0.0001), and the addition of clopidogrel 300 mg
      did not inhibit platelet aggregation any more than tirofiban alone throughout the
      24 h (group C vs. A: P = NS). All of the changes over time within each group were
      highly significant (P < 0.0001). CONCLUSIONS: Tirofiban leads to greater early
      inhibition of platelet aggregation but less suppression of P-selectin expression
      than clopidogrel 600 mg. The addition of clopidogrel to tirofiban does not add
      any anti-aggregatory effect, but reduces P-selectin expression, thus likely
      adding a significant biological and clinical protective effect and providing a
      rationale for the combined use of the two drugs.

PMID- 18049796
TI  - Functional analysis of rice HOMEOBOX4 (Oshox4) gene reveals a negative function
      in gibberellin responses.
AB  - The homeodomain-leucine zipper (HD-Zip) putative transcription factor genes are
      divided into 4 families. In this work, we studied the function of a rice HD-Zip I
      gene, H OME O BO X4 (Oshox4). Oshox4 transcripts were detected in leaf and floral
      organ primordia but excluded from the shoot apical meristem and the protein was
      nuclear localized. Over-expression of Oshox4 in rice induced a semi-dwarf
      phenotype that could not be complemented by applied GA3. The over-expression
      plants accumulated elevated levels of bioactive GA, while the GA catabolic gene
      GA2ox3 was upregulated in the transgenic plants. In addition, over-expression of
      Oshox4 blocked GA-dependent alpha-amylase production. However, down-regulation of
      Oshox4 in RNAi transgenic plants induced no phenotypic alteration. Interestingly,
      the expression of YAB1 that is involved in the negative feedback regulation of
      the GA biosynthesis was upregulated in the Oshox4 over-expressing plants. One
      hybrid assays showed that Oshox4 could interact with YAB1 promoter in yeast. In
      addition, Oshox4 expression was upregulated by GA. These data together suggest
      that Oshox4 may be involved in the negative regulation of GA signalling and may
      play a role to fine tune GA responses in rice.

PMID- 18049797
TI  - Molecular genetics of puroindolines and related genes: regulation of expression,
      membrane binding properties and applications.
AB  - Kernel texture of wheat is a primary determinant of its technological properties.
      Soft kernel texture phenotype results when the Puroindoline a and Puroindoline b
      genes are present and encode the wild-type puroindolines PINA and PINB,
      respectively, and various mutations in either or both gene(s) result in hard
      phenotypes. A wealth of information is now available that furthers our
      understanding regarding the spatial and temporal regulation of expression of
      Puroindoline genes. Through the use of model membranes and synthetic peptides we
      also have a clearer understanding of the significance of the cysteine backbone,
      the tryptophan-rich domain (TRD) and the helicoid tertiary structures of PIN
      proteins in relation to their membrane-active properties. Many studies suggest
      individual yet co-operative modes of action of the PIN proteins in determining
      kernel texture, and significant evidence is accumulating that the proteins have
      in vivo and in vitro antimicrobial activities, shedding light on the biological
      roles of this unique ensemble of proteins. The puroindolines are now being
      explored for grain kernel texture modifications as well as antimicrobial
      activities.

PMID- 18049798
TI  - Molecular genetics of puroindolines and related genes: allelic diversity in wheat
      and other grasses.
AB  - The hardness or texture of cereal grains is a primary determinant of their
      technological and processing quality. Among members of the Triticeae, most
      notably wheat, much of the variation in texture is controlled by a single locus
      comprised of the Puroindoline a, Puroindoline b and Grain Softness Protein-1 (Gsp
      1) genes. Puroindolines confer the three major texture classes of soft and hard
      common wheat and the very hard durum wheat. The protein products of these genes
      interact with lipids and are associated with the surface of isolated starch (as a
      protein fraction known as 'friabilin'). During the past ten years a great
      diversity of alleles of both Puroindoline genes have been discovered and
      significant advances made in understanding the relationship between the gene
      presence/absence, sequence polymorphism and texture of cereal grains. Efforts
      have also focussed on Puroindoline and Gsp-1 genes in diploid progenitors, other
      Triticeae grasses and synthetic wheats in order to understand the evolution of
      this gene family and find potentially useful variants. The puroindoline
      homologues in other cereals such as rye and barley are also receiving attention.
      This work summarises new developments in molecular genetics of puroindolines in
      wheat and related Triticeae grasses, and the related genes in other cereals.

PMID- 18049799
TI  - The association between selected risk factors for pancreatic cancer and the
      expression of p53 and K-ras codon 12 mutations.
AB  - BACKGROUND: Pancreatic cancer is a major contributor to cancer mortality. Studies
      suggest that a few risk factors, including cigarette smoking, body mass index,
      having a relative with pancreatic cancer, and diabetes may be related to
      pancreatic cancer risk. AIM OF THE STUDY: We conducted a case-control study in
      southeastern Michigan to examine the relation between the above mentioned risk
      factors and mutations of the K-ras oncogene and p53 tumor suppressor gene.
      METHODS: Two hundred forty-five patients with newly diagnosed pancreatic cancer
      and 420 general population controls were enrolled in the study. For this
      analysis, all case subjects were restricted to the pancreatic cancer patients
      that had tissue blocks available for study (n = 51). In-person interviews were
      conducted to ascertain information on demographic and lifestyle factors. Adjusted
      logistic regression analyses were conducted to compare various subject
      characteristics of pancreatic cancer patients with K-ras and p53 mutations and
      their subtypes to the characteristics of the general population controls.
      RESULTS: Smoking (adjusted odds ratio [aOR] = 2.0; 95% confidence interval
      [95%CI] = 0.9-4.3) and diabetes diagnosed 5 or more years before interview (aOR =
      3.4; 95%CI = 1.3-8.8) were associated with pancreatic cancer patients positive
      for K-ras codon 12 mutations, but not with pancreatic cancer patients negative
      for K-ras codon 12 mutations. On the other hand, none of the examined risk
      factors were meaningfully related to patients with p53 mutations. CONCLUSIONS:
      This study suggests that some recognized risk factors for pancreatic cancer may
      also be associated with K-ras codon 12 mutations. However, further large-scale
      studies are warranted.

PMID- 18049800
TI  - Cloning and sequencing of an original gene encoding a maltogenic amylase from
      Bacillus sp. US149 strain and characterization of the recombinant activity.
AB  - A gene encoding maltogenic amylase from acidic Bacillus sp. US149 (maUS149) was
      cloned, sequenced and over-expressed in Escherichia coli. The nucleotide sequence
      analysis revealed an open reading frame (ORF) of 1749 bp encoding a protein of
      582 residues. The alignment of deduced amino acid sequence revealed a relatively
      low homology with the already reported maltogenic amylases. In fact, its highest
      identity, of only 60%, was found with the maltogenic amylase of Thermus sp.
      IM6501. The recombinant enzyme (MAUS149) was found to be intracellular and was
      purified to homogeneity from the cell crude extract with a yield of 23%.
      According to PAGE analysis, under reducing and non-reducing conditions, the
      recombinant enzyme has an apparent molecular weight of 135 kDa and is composed of
      two identical subunits of 67.5 kDa each. The maximum activity was obtained at 40
      degrees C and pH 6.5. MAUS149 could be classified as a maltogenic amylase since
      it produces mainly maltose from starch, maltose and glucose from beta
      cyclodextrin, and panose from pullulan.

PMID- 18049804
TI  - Founding the first hernia center in Turkey.
AB  - For years, centers dedicated to hernia surgery have been operating in North
      America and Europe. However, such centers have not been available to patients in
      most other countries, including Turkey. In 2006, the first Turkish center devoted
      to hernia surgery, the "Ankara Hernia Center", was opened. In this paper, we
      present general information about the center's construction, staff, practice,
      patient profiles, and future goals.

PMID- 18049805
TI  - ATP synthesis by decarboxylation phosphorylation.
AB  - Adenosine triphosphate (ATP) is used as a general energy source by all living
      cells. The free energy released by hydrolyzing its terminal phosphoric acid
      anhydride bond to yield ADP and phosphate is utilized to drive various energy
      consuming reactions. The ubiquitous F(1)F(0) ATP synthase produces the majority
      of ATP by converting the energy stored in a transmembrane electrochemical
      gradient of H(+) or Na(+) into mechanical rotation. While the mechanism of ATP
      synthesis by the ATP synthase itself is universal, diverse biological reactions
      are used by different cells to energize the membrane. Oxidative phosphorylation
      in mitochondria or aerobic bacteria and photophosphorylation in plants are well
      known processes. Less familiar are fermentation reactions performed by anaerobic
      bacteria, wherein the free energy of the decarboxylation of certain metabolites
      is converted into an electrochemical gradient of Na(+) ions across the membrane
      (decarboxylation phosphorylation). This chapter will focus on the latter
      mechanism, presenting an updated survey on the Na(+)-translocating decarboxylases
      from various organisms. In the second part, we provide a detailed description of
      the F(1)F(0) ATP synthases with special emphasis on the Na(+)-translocating
      variant of these enzymes.

PMID- 18049806
TI  - [HPV and skin neoplasia].
AB  - Human papillomaviruses (HPV) induce benign and malignant tumors of skin and
      mucosa. Non-melanoma skin cancer (NMSC) is the most frequent malignancy in fair
      skinned populations, particularly frequent in countries with high sun exposure
      and in immunosuppressed patients. The high prevalence of Beta-HPV in skin tumors
      renewed interest in a possible etiologic role of HPV. In contrast to cervical
      cancer, the presence of HPV is probably not mandatory for maintenance of the
      malignant phenotype of skin cancer cells, since only low copy numbers of HPV DNA
      persist in skin cancers. Higher viral loads in actinic keratoses are compatible
      with a carcinogenic role of cutaneous HPV in early phases of NMSC development.
      There is some evidence from case-control studies for an increased risk of
      cutaneous squamous cell carcinoma related to beta-HPV infection. HPV8 is clearly
      carcinogenic in transgenic mice. At the molecular level, oncogenic activities of
      beta-HPV have been attributed to effective inhibition of apoptosis and
      interference with DNA repair pathways by viral E6 proteins. In addition E7
      proteins deregulate the cell cycle and enhance invasive growth.

PMID- 18049807
TI  - [Minimally invasive unicondylar knee arthroplasty with simultaneous ACL
      reconstruction : treatment of medial compartment osteoarthritis and cruciate
      ligament defect].
AB  - BACKGROUND: Low postoperative pain level, decreased length of hospital stay and
      accelerated rehabilitation are the major benefits of unicondylar knee
      arthroplasty. Especially in comparably young, not yet retired and still active
      patients with an isolated medial gonarthrosis, these prostheses offer many
      advantages. However, one important requirement to be treated with such implants
      is a well functioning stability system of the muscles and ligaments. Thus in
      patients with degenerated or destroyed anterior cruciate ligaments it is
      contraindicated to use this method. In order to still take advantage of this
      therapy for treatment of isolated arthrosis, reestablishment of the
      proprioceptive structures through simultaneous or staged ACL reconstruction is
      mandatory. PATIENTS AND METHODS: Pursuing this goal we performed unicondylar knee
      arthroplasty with simultaneous ACL reconstruction on eligible patients. Between
      2003 and 2006 we treated 32 knees with this combined surgery and followed them
      for a mean of 31 months (range: 10-38). RESULTS: The mean Knee Society Score
      significantly improved from 83.2 (44-103) to 167.6 (145-177) at a mean follow-up
      of 31 months (10-38). CONCLUSIONS: Preliminary results of this short-term follow
      up are promising. Especially the predominant number of patients who were able to
      return to work soon after rehabilitation and the significantly improved score
      postoperatively reflect the benefits of this prosthesis system in select
      patients. However, long-term follow-up and larger case numbers are necessary to
      confirm these encouraging results in the future.

PMID- 18049808
TI  - [Varicocele and pubertal testicular growth. A prospective study].
AB  - BACKGROUND: We prospectively assessed male students in the 4th and 8th forms to
      see whether varicoceles affect testicular growth. PARTICIPANTS AND METHODS:
      Ultrasound measurements were done in 778 boys to define testicular size according
      to the different pubertal stages. Seven hundred boys had a left or bilateral
      varicocele; 257 children and 287 adolescents with unilateral varicoceles were
      assessed for testicular size discrepancies in relationship to the varicocele size
      and the Doppler grades of venous reflux in the upright and supine positions.
      RESULTS: Rapid testicular growth occurred at puberty. By comparing the
      frequencies and extent of ipsilateral growth failures in adolescents, we noted
      significant differences among the varicocele grades. A volume loss of >or=15% was
      associated with the higher varicocele grades and the reflux grades in the supine
      position. CONCLUSION: Varicoceles may impair testicular growth at puberty. The
      severity of volume loss depends on the varicocele size and the related
      alterations in circulatory flow.

PMID- 18049809
TI  - [The role of lubrication in transurethral electrical resection].
AB  - Transurethral resection inevitably leads to thermal as well as mechanical stress
      on the urethra, and it is important to reduce both. This can be achieved by using
      a suitable lubricant. Measurements in saline irrigation fluid as long as 30 years
      ago showed that the distribution of high-frequency current in the region of the
      urethra during transurethral electrical resection depends on the different
      resection systems, i.e. the varying placement of the neutral electrode.
      Application of a lubricant with appropriate conductivity makes it possible to
      avoid dangerous current surges in the region of the urethra. When it is used for
      reduction of the mechanical stress on the urethra, the consistency and amount of
      the lubricant used and also the frequency of application are important.
      Theoretically, even in the case of the so-called bipolar transurethral resection
      procedure in saline used today, the possibility that the electric current will
      cause thermal damage to the urethra is as great as when a conventional monopolar
      resection procedure using nonconductive irrigation fluid is performed.

PMID- 18049810
TI  - Attenuation by methyl mercury and mercuric sulfide of pentobarbital induced
      hypnotic tolerance in mice through inhibition of ATPase activities and nitric
      oxide production in cerebral cortex.
AB  - This study is aimed at exploring the possible mechanism of hypnosis-enhancing
      effect of HgS or cinnabar (a traditional Chinese medicine containing more than
      95% HgS) in mice treated with pentobarbital. We also examined whether the effect
      of HgS is different from that of the well-known methyl mercury (MeHg). After a
      short period (7 days) of oral administration to mice, a nontoxic dose (0.1 g/kg)
      of HgS not only significantly enhanced pentobarbital-induced hypnosis but also
      attenuated tolerance induction; while a higher dose (1 g/kg) of HgS or cinnabar
      exerted an almost irreversible enhancing effect on pentobarbital-hypnosis similar
      to that of MeHg (2 mg/kg) tested, which was still effective even after 10 or 35
      days cessation of administration. To study comparatively the effects of different
      mercury forms from oral administration of MeHg and HgS on membrane ATPase
      activities of experimental mice, analysis of the Hg content in the cerebral
      cortex revealed that correlated with the decrease of Na(+)/K(+)-ATPase and Ca(2+)
      ATPase activities. Furthermore, NO levels of blood but not that of cerebral
      cortex were also decreased by mercuric compounds. Although pentobarbital alone
      enhanced cytochrome p450-2C9 in time dependent manner, all of mercurial compounds
      tested had no such effect. All of these findings indicated that the mercurial
      compounds including cinnabar, HgS and MeHg exert a long-lasting enhancing
      hypnotic activity without affecting pentobarbital metabolism, which provides
      evidence-based sedative effect of cinnabar used in Chinese traditional medicine
      for more than 2,000 years. The nontoxic HgS dosing (0.1 g/kg/day) for consecutive
      7 days is perhaps useful for delaying or preventing pentobarbital-tolerance.

PMID- 18049811
TI  - Does context influence the duration of locomotor sensitization to ethanol in
      female DBA/2J mice?
AB  - RATIONALE: Repeated exposure to ethanol produces a progressive increase in
      locomotor sensitivity, referred to as locomotor sensitization. Locomotor
      sensitization may persist for some time after termination of repeated drug
      exposure, and context appears to facilitate expression of the behavioral
      phenomenon. However, many unanswered questions remain concerning the persistence
      of and degree to which context influences locomotor sensitization to alcohol
      (ethanol). OBJECTIVES: The goal of the present work was to determine the duration
      of locomotor sensitization to ethanol and the degree to which context dependence
      positively influences the induction, expression, and persistence of the
      behavioral phenomenon in female DBA/2J mice. MATERIALS AND METHODS: Sensitized
      (with or without ethanol-paired exposure to the testing chamber) and non
      sensitized saline control mice were left undisturbed in their home cages until
      subsequent ethanol challenge and testing in the locomotor activity testing
      chambers 7, 14, 21, 28, 42, 56, and/or 70 days after cessation of the ethanol
      sensitization procedure. Retro-orbital sinus bloods were sampled to determine
      whether the sensitization procedure had altered blood ethanol clearance rates.
      RESULTS: Locomotor sensitization persisted through post-sensitization day 14, and
      repeated paring of the drug and testing context prolonged the expression of this
      phenomenon through at least post-sensitization day 28. Blood ethanol
      concentrations did not differ. CONCLUSIONS: Locomotor sensitization to ethanol
      persists for some time after cessation of repeated ethanol exposure, and the
      association of contextual cues with the ethanol experience lengthens this
      persistence. The present data lay the groundwork for investigations into the
      neuroadaptive changes that underlie locomotor sensitization to ethanol in mice.

PMID- 18049813
TI  - The study of surface properties of an IgE-sensitive aptasensor using an acoustic
      method.
AB  - We applied the acoustic transverse shear mode (TSM) method for study of the
      surface properties of a DNA aptasensor that specifically binds human
      immunoglobulin E (IgE). The biotinylated 45-mer DNA aptamers were immobilized on
      the surface of a self-assembled layer composed of a mixture of polyamidoamine
      dendrimers of the fourth generation with 1-hexadecanetiol covered by neutravidin.
      Using the TSM method, we studied the kinetics of changes of the series resonant
      frequency, f(s), and the motional resistance, R(m), of a quartz crystal
      transducer, used as a support for formation of the sensing layer. We have shown
      that attachment of the biotinylated DNA aptamers onto the surface covered by
      neutravidin results in a decrease of f(s), but in an increase of R(m). Similar
      changes of f(s) and R(m) were observed following addition of IgE. This suggests
      the contribution of friction forces to the crystal oscillation, which was taken
      into account in the calculation of the mass changes at the sensor surface
      following binding processes.

PMID- 18049812
TI  - Hippocampal endocannabinoids inhibit spatial learning and limit spatial memory in
      rats.
AB  - RATIONALE: As exogenous cannabinoid agonists impair memory formation, could it be
      that antagonists have opposing effects and act as memory-enhancing drugs?
      OBJECTIVES: Here, we studied the effects of the cannabinoid antagonist SR141716A
      (SR; Rimonabant) on spatial learning and memory formation and assessed the
      possible involvement of hippocampal CB(1) receptor in these actions. MATERIALS
      AND METHODS: In the water maze, spatial reference memory was probed using
      different training protocols followed by assessment of behavioral flexibility.
      The CB(1) receptor antagonist SR (3 mg/kg) was intraperitoneally administered
      before or immediately after training in experiment 1, or via minipumps
      intrahippocampally (0.89 ng and 0.089 ng/day) either during or after spatial
      learning, or subcutaneously in experiment 2. RESULTS: In experiment 1, systemic
      SR impaired spatial learning when given intraperitoneally (ip) before training
      coincident with increasing swim speed and thigmotaxis. Pretraining before drug
      treatment eliminated these effects while post-training injections had no effect.
      In experiment 2, intrahippocampal infusion of 0.089 ng SR during training
      enhanced acquisition learning, but did not affect long-term consolidation of
      spatial memory. In contrast, subcutaneous infusion of SR via minipumps had no
      effect. Post-training infusion of SR did not affect reversal learning, but short
      term memory (1 h post-training) was weaker, and long-term memory for the reversal
      platform location was enhanced. CONCLUSIONS: Systemic Rimonabant-induced deficits
      are due to anxiogenic properties of the drug. The difference between
      administration regimes is discussed in terms of CB(1) receptor blockade in
      multiple non-memory and memory-related brain regions and the possibility that
      selective inactivation of hippocampal CB(1) receptors may be memory enhancing.

PMID- 18049814
TI  - (239, 240, 241)Pu fingerprinting of plutonium in western US soils using ICPMS:
      solution and laser ablation measurements.
AB  - Sector field inductively coupled plasma mass spectrometry (SF-ICPMS) has been
      used with analysis of solution samples and laser ablation (LA) of
      electrodeposited alpha sources to characterize plutonium activities and atom
      ratios prevalent in the western USA. A large set of surface soils and attic dusts
      were previously collected from many locations in the states of Nevada, Utah,
      Arizona, and Colorado; specific samples were analyzed herein to characterize the
      relative contributions of stratospheric fallout vs. Nevada Test Site (NTS)
      plutonium. This study illustrates two different ICPMS-based analytical strategies
      that are successful in fingerprinting Pu in environmental soils and dusts. Two
      specific datasets have been generated: (1) soils are leached with HNO3-HCl,
      converted into electrodeposited alpha sources, counted by alpha spectrometry,
      then re-analyzed using laser ablation SF-ICPMS; (2) samples are completely
      dissolved by treatment with HNO3-HF-H3BO3, Pu fractions are prepared by
      extraction chromatography, and analyzed by SF-ICPMS. Optimal laser ablation and
      ICPMS conditions were determined for the re-analysis of archived alpha
      spectrometry "planchette" sources. The best ablation results were obtained using
      a large spot size (200 microm), a defocused beam, full repetition rate (20 Hz)
      and scan rate (200 microm s(-1)); LA-ICPMS data were collected with a rapid
      electrostatic sector scanning experiment. Less than 10% of the electroplated
      surface area is consumed in the LA-ICPMS analysis, which would allow for multiple
      re-analyses. Excellent agreement was found between (239+240)Pu activities
      determined by LA-ICPMS vs. activity results obtained by alpha spectrometry for
      the same samples ten years earlier. LA-ICPMS atom ratios for 240Pu/239Pu and
      241Pu/239Pu range from 0.038-0.132 and 0.00034-0.00168, respectively, and plot
      along a two-component mixing line (241Pu/239Pu = 0.013 [240Pu/239Pu] - 0.0001; r2
      = 0.971) with NTS and global fallout end-members. A rapid total dissolution
      procedure, followed by extraction chromatography and SF-ICPMS solution Pu
      analysis, generates excellent agreement with certified (239+240)Pu activities for
      standard reference materials NIST 4350b, NIST 4353, NIST 4357, and IAEA 385.
      (239+240)Pu activities and atom ratios determined by total dissolution reveal
      isotopic information in agreement with the LA-ICPMS dataset regarding the
      ubiquitous mixing of NTS and stratospheric fallout Pu sources in the regional
      environment. For several specific samples, the total dissolution method reveals
      that Pu is incompletely recovered by simpler HNO3-HCl leaching procedures, since
      some of the Pu originating from the NTS is contained in refractory siliceous
      particles.

PMID- 18049815
TI  - Selection of fluorescent aptamer beacons that light up in the presence of zinc.
AB  - In order to generate nucleic acid biosensors that could undergo a reversible
      conformation change in the presence of the metal zinc, a random sequence pool of
      single-stranded DNA was immobilized on an oligonucleotide affinity column. In the
      presence of zinc, those species that underwent a conformational change were
      released from the column, collected, and amplified. A series of negative and
      positive selections refined the metal specificity of the selected aptamer
      beacons. Since the aptamer beacons contained a fluorophore, while the bound
      oligonucleotide contained a quencher, zinc binding also resulted in an increase
      in fluorescence. One of the selected beacons, Zn-6m2, bound zinc in the low
      micromolar range, gave a dose-dependent fluorescence signal, and showed an
      approximately sixfold increase in fluorescence on zinc binding. While some cross
      reactivity with cadmium was observed, it should nonetheless prove possible to use
      the novel selection method to generate and tune the specificity of a variety of
      reversible metal biosensors. Such biosensors could potentially be used for
      continuous monitoring of metals in environmental samples.

PMID- 18049816
TI  - Evidence for direct projections from the basal nucleus of the amygdala to
      retrosplenial cortex in the Macaque monkey.
AB  - The role of the primate retrosplenial cortex (RSC) in memory processing and
      spatial navigation has been well established. Recently, processing emotionally
      salient information has been attributed to the RSC as well. Little anatomical
      data, however, exist linking the RSC with known emotional processing centers
      within the brain. The amygdala has been implicated as a substrate for modulating
      memory for emotionally salient events; yet no study to date has demonstrated that
      this area has a direct connection in the primate brain. With modern retrograde
      tracer injections into the RSC and adjacent cortical areas of the monkey (Macaca
      fascicularis), we demonstrate that there are efferent projections from the basal
      nucleus of the amygdala to the RSC and area 31. These projections offer
      anatomical data supporting the hypothesis that the RSC might receive emotionally
      salient input directly from the amygdala and suggest a role for the RSC as a node
      within a neural system potentially capable of integrating emotional information
      for use in memory or other cognitive processes.

PMID- 18049817
TI  - Estimation of binding parameters for the protein-protein interaction using a site
      directed spin labeling and EPR spectroscopy.
AB  - Sensitivity of the electron paramagnetic resonance (CW EPR) to molecular tumbling
      provides potential means for studying processes of molecular association. It uses
      spin-labeled macromolecules, whose CW EPR spectra may change upon binding to
      other macromolecules. When a spin-labeled molecule is mixed with its liganding
      partner, the EPR spectrum constitutes a linear combination of spectra of the
      bound and unbound ligand (as seen in our example of spin-labeled cytochrome c(2)
      interacting with cytochrome bc(1) complex). In principle, the fraction of each
      state can be extracted by the numerical decomposition of the spectrum; however,
      the accuracy of such decomposition may often be compromised by the lack of the
      spectrum of the fully bound ligand, imposed by the equilibrium nature of
      molecular association. To understand how this may affect the final estimation of
      the binding parameters, such as stoichiometry and affinity of the binding, a
      series of virtual titration experiments was conducted. Our non-linear regression
      analysis considered a case in which only a single class of binding sites exists,
      and a case in which classes of both specific and non-specific binding sites co
      exist. The results indicate that in both models, the error due to the unknown
      admixture of the unbound ligand component in the EPR spectrum causes an
      overestimation of the bound fraction leading to the bias in the dissociation
      constant. At the same time, the stoichiometry of the binding remains relatively
      unaffected, which overall makes the decomposition of the EPR spectrum an
      attractive method for studying protein-protein interactions in equilibrium. Our
      theoretical treatment appears to be valid for any spectroscopic techniques
      dealing with overlapping spectra of free and bound component.

PMID- 18049819
TI  - Transient activation of tumor-associated T-effector/memory cells promotes tumor
      eradication via NK-cell recruitment: minimal role for long-term T-cell immunity
      in cure of metastatic disease.
AB  - Local delivery of IL-12 and GM-CSF to advanced primary tumors results in T- and
      NK-cell-dependent cure of disseminated disease in a murine spontaneous lung
      metastasis model. Post-therapy functional dynamics of cytotoxic T- and NK-cells
      were analyzed in primary and metastatic tumors to determine the specific roles of
      each subset in tumor eradication. Time-dependent depletion of CD8+ T and NK-cells
      demonstrated that CD8+ T-cells were critical to eradication of metastatic tumors
      within 3 days of treatment, but not later. In contrast, NK-cells were found to be
      essential to tumor regression for at least 10 days after cytokine delivery.
      Analysis of tumor-infiltrating lymphocyte populations in post-therapy primary
      tumors demonstrated that treatment resulted in the activation of tumor-associated
      CD8+ T-cells within 24 h as determined by IFNgamma and perforin production. T
      cell activity peaked between days 1 and 3 and subsided rapidly thereafter.
      Activation was not accompanied with an increase in cell numbers suggesting that
      treatment mobilized pre-existing T-effector/memory cells without inducing
      proliferation. In contrast, therapy resulted in a > or = 3-fold enhancement of
      both the quantity and the cytotoxic activity of NK-cells in primary and
      metastatic tumors on day 3 post-therapy. NK-cell activity was also transient and
      subsided to pre-therapy levels by day 5. Depletion of CD4+ and CD8+ T-cells prior
      to treatment completely abrogated NK-cell infiltration into primary and
      metastatic tumors demonstrating the strict dependence of NK-cell recruitment on
      pre-existing T-effector/memory cells. Treatment failed to induce significant NK
      cell infiltration in IFNgamma-knockout mice establishing the central role of
      IFNgamma in NK-cell chemotaxis to tumors. These data show that transient
      activation of tumor-associated T-effector/memory and NK-cells, but not long-term
      CD8+ T-cell responses, are critical to suppression of metastatic disease in this
      model; and reveal a novel role for preexisting adaptive T-cell immunity in the
      recruitment of innate effectors to tumors.

PMID- 18049818
TI  - Trans-species polymorphism and evidence of selection on class II MHC loci in tuco
      tucos (Rodentia: Ctenomyidae).
AB  - Balancing selection acting over the evolutionary history of a lineage can result
      in the retention of alleles among species for longer than expected under neutral
      evolution. The associated pattern of trans-species polymorphism, in which similar
      or even identical alleles are shared among species, is often used to infer that
      balancing selection has occurred. The genes of the major histocompatibility
      complex (MHC) are thought to be subject to balancing selection that maintains
      alleles associated with response to specific pathogens. To explore the role of
      balancing selection in shaping MHC diversity in ctenomyid rodents, we examined
      allelic variability at the class II DRB and DQA loci in 18 species in the genus
      Ctenomys. Previous studies of four of these species had revealed significant
      within-population evidence of positive selection on MHC loci. The current study
      expands upon these analyses to (1) evaluate among-species evidence of positive
      selection and (2) explore the potential for balancing selection on MHC genes.
      Interspecific nucleotide sequence variation revealed significant evidence of
      positive selection on the DRB and DQA loci. At the same time, comparisons of
      phylogenetic trees for these MHC loci with a putative species tree based on
      mitochondrial sequence data revealed multiple examples of trans-specific
      polymorphism, including sharing of identical DRB and DQA alleles among distantly
      related species of Ctenomys. These findings suggest that MHC genes in these
      animals have historically been subject to balancing selection and yield new
      insights into the complex suite of forces shaping MHC diversity in free-living
      vertebrates.

PMID- 18049821
TI  - Phonotactic response of female crickets on the Kramer treadmill: methodology,
      sensory and behavioural implications.
AB  - Since population-level variation in female mating preferences can shape
      intraspecific communication systems within the context of sexual selection it is
      essential to quantify these preferences and their sources of variation. We
      calculated individual female response functions for four male calling song traits
      in the field cricket Gryllus bimaculatus, by performing untethered phonotaxis
      measurements on a spherical locomotor compensator (Kramer treadmill). Firstly, we
      quantify the population-level sources of phonotactic variation and correct for
      factors that adversely affect this measurement. Secondly, we develop methodology
      for the characterisation of individual female phonotactic response functions
      suitable for population-level analyses and demonstrate the applicability of our
      method with respect to recent literature on Orthopteran acoustic communication.
      Phonotaxis towards a preferred stimulus on different occasions is highly
      repeatable, with lower repeatabilities away from the most preferred signal
      traits. For certain male signal traits, female preference and selectivity are
      highly repeatable. Although phonotactic response magnitude deteriorated with age,
      preference functions of females remained the same during their lifetimes.
      Finally, the limitations of measuring phonotaxis using a spherical locomotor
      compensator are described and discussed with respect to the estimation of the
      selectivity of female response.

PMID- 18049822
TI  - Primary pleural synovial sarcoma presenting as a multiloculated cyst in an
      adolescent.
AB  - Primary pleural synovial sarcoma (PPSS) is a rare pleural malignancy with a grave
      prognosis. Most cases present as a well-circumscribed mass with foci of
      haemorrhage and necrosis. We present an unusual case in a Nepalese boy that
      presented as a multiloculated cyst mimicking hydatid disease. The diagnosis was
      confirmed by histology and cytogenetic analysis.

PMID- 18049823
TI  - Nonlinearities make a difference: comparison of two common Hill-type models with
      real muscle.
AB  - Compared to complex structural Huxley-type models, Hill-type models
      phenomenologically describe muscle contraction using only few state variables.
      The Hill-type models dominate in the ever expanding field of musculoskeletal
      simulations for simplicity and low computational cost. Reasonable parameters are
      required to gain insight into mechanics of movement. The two most common Hill
      type muscle models used contain three components. The series elastic component is
      connected in series to the contractile component. A parallel elastic component is
      either connected in parallel to both the contractile and the series elastic
      component (model [CC+SEC]), or is connected in parallel only with the contractile
      component (model [CC]). As soon as at least one of the components exhibits
      substantial nonlinearities, as, e.g., the contractile component by the ability to
      turn on and off, the two models are mechanically different. We tested which model
      ([CC+SEC] or [CC]) represents the cat soleus better. Ramp experiments consisting
      of an isometric and an isokinetic part were performed with an in situ cat soleus
      preparation using supramaximal nerve stimulation. Hill-type models containing
      force-length and force-velocity relationship, excitation-contraction coupling and
      series and parallel elastic force-elongation relations were fitted to the data.
      To test which model might represent the muscle better, the obtained parameters
      were compared with experimentally determined parameters. Determined in situations
      with negligible passive force, the force-velocity relation and the series elastic
      component relation are independent of the chosen model. In contrast to model
      [CC+SEC], these relations predicted by model [CC] were in accordance with
      experimental relations. In conclusion model [CC] seemed to better represent the
      cat soleus contraction dynamics and should be preferred in the nonlinear
      regression of muscle parameters and in musculoskeletal modeling.

PMID- 18049824
TI  - Characteristic phenotype of immortalized periodontal cells isolated from a Marfan
      syndrome type I patient.
AB  - The periodontal ligament (PDL) is situated between the tooth root and alveolar
      bone, thereby supporting the tooth, and is composed of collagen and elastic
      system fibers. Marfan syndrome type I (MFS1, MIM #154700) is caused by mutations
      in FBN1 encoding fibrillin-1, which is a major microfibrillar protein of elastic
      system fibers. MFS1 is characterized by tall stature, aortic/mitral valve
      prolapse, and ectopia lentis and is occasionally accompanied by severe
      periodontitis. Since little is known about the biological functions of elastic
      system fibers in PDLs and the pathogenesis of the periodontitis in MFS1, PDL
      cells were isolated from an MFS1 patient with a heterozygous missense mutation in
      a calcium-binding epidermal-growth-factor-like domain of FBN1. Isolated PDL cells
      were immortalized by transducing a retrovirus carrying genes for the human
      Polycomb group protein, Bmi-1, and human telomerase reverse transcriptase.
      Immortalized PDL cells from the MFS1 patient (termed M-HPL1) and those of a
      healthy volunteer (termed HPDL2) both expressed various PDL-related genes. The
      growth and attachment of M-HPL1 and HPDL2 to hydroxyapatite particles were
      comparable. However, when M-HPL1 were transplanted with hydroxyapatite particles
      into immunodeficient mice, disorganized cell alignment and irregular microfibril
      assembly were noted. The activation of the signaling of transforming grwoth
      factor-beta (TGF-beta) is thought to cause the pathogenesis for lung and
      cardiovascular abnormalities in MFS1. Interestingly, M-HPL1 shows a higher level
      of activated TGF-beta than HPDL2. Thus, M-HPL1 represent a powerful tool for
      clarifying the biological roles of elastic system fibers in PDL and the
      pathogenesis of periodontitis in MFS1. Our findings also suggest that FBN1
      regulates cell alignment and microfibril assembly in PDLs.

PMID- 18049825
TI  - Leaf litter input mediates tadpole performance across forest canopy treatments.
AB  - Understanding the mechanisms limiting the distributions of organisms is necessary
      for predicting changes in community composition along habitat gradients. In many
      areas of the USA, land originally cleared for agriculture has been undergoing a
      process of reforestation, creating a gradient of canopy cover. For small
      temporary wetlands, this gradient can alter abiotic conditions and influence the
      resource base of wetland food webs by affecting litter inputs. As distributions
      of amphibians and many other temporary wetland taxa correlate with canopy cover,
      we experimentally manipulated shade levels and litter types in pond mesocosms to
      explore mechanisms limiting species performance in wetlands with canopy cover.
      Most differences between ponds were mediated by litter type rather than direct
      effects of shading. Although all three amphibian species tested are open-canopy
      specialists, spring peepers were the only species to show decreased survival in
      shaded ponds. Pond litter type generally had strong effects on growth and
      development rates, with tadpoles of two species in grass litter ponds growing to
      twice the size of, and metamorphosing 7 days earlier than, those in leaf litter
      ponds. Contrary to our initial hypothesis, shade level and litter type showed
      very few significant interactions. Our results indicate that the effects of
      shading cannot be considered in isolation of vegetation changes in pond basins
      when evaluating the effects of forest succession on temporary pond communities.

PMID- 18049826
TI  - Stem and leaf hydraulics of congeneric tree species from adjacent tropical
      savanna and forest ecosystems.
AB  - Leaf and stem functional traits related to plant water relations were studied for
      six congeneric species pairs, each composed of one tree species typical of
      savanna habitats and another typical of adjacent forest habitats, to determine
      whether there were intrinsic differences in plant hydraulics between these two
      functional types. Only individuals growing in savanna habitats were studied. Most
      stem traits, including wood density, the xylem water potential at 50% loss of
      hydraulic conductivity, sapwood area specific conductivity, and leaf area
      specific conductivity did not differ significantly between savanna and forest
      species. However, maximum leaf hydraulic conductance (K (leaf)) and leaf
      capacitance tended to be higher in savanna species. Predawn leaf water potential
      and leaf mass per area were also higher in savanna species in all congeneric
      pairs. Hydraulic vulnerability curves of stems and leaves indicated that leaves
      were more vulnerable to drought-induced cavitation than terminal branches
      regardless of genus. The midday K (leaf) values estimated from leaf vulnerability
      curves were very low implying that daily embolism repair may occur in leaves. An
      electric circuit analog model predicted that, compared to forest species, savanna
      species took longer for their leaf water potentials to drop from predawn values
      to values corresponding to 50% loss of K (leaf) or to the turgor loss points,
      suggesting that savanna species were more buffered from changes in leaf water
      potential. The results of this study suggest that the relative success of savanna
      over forest species in savanna is related in part to their ability to cope with
      drought, which is determined more by leaf than by stem hydraulic traits.
      Variation among genera accounted for a large proportion of the total variance in
      most traits, which indicates that, despite different selective pressures in
      savanna and forest habitats, phylogeny has a stronger effect than habitat in
      determining most hydraulic traits.

PMID- 18049827
TI  - Tree fern trunks facilitate seedling regeneration in a productive lowland
      temperate rain forest.
AB  - Seedling regeneration on forest floors is often impaired by competition with
      established plants. In some lowland temperate rain forests, tree fern trunks
      provide safe sites on which tree species establish, and grow large enough to take
      root in the ground and persist. Here we explore the competitive and facilitative
      effects of two tree fern species, Cyathea smithii and Dicksonia squarrosa, on the
      epiphytic regeneration of tree species in nutrient-rich alluvial forests in New
      Zealand. The difficulties that seedlings have in establishing on vertical tree
      fern trunks were indicated by the following observations. First, seedling
      abundance was greatest on the oldest sections of tree fern trunks, near the base,
      suggesting that trunks gradually recruited more and more seedlings over time, but
      many sections of trunk were devoid of seedlings, indicating the difficulty of
      establishment on a vertical surface. Second, most seedlings were from small
      seeded species, presumably because smaller seeds can easily lodge on tree fern
      trunks. Deer browsing damage was observed on 73% of epiphytic seedlings growing
      within 2 m of the ground, whereas few seedlings above that height were browsed.
      This suggests that tree ferns provide refugia from introduced deer, and may slow
      the decline in population size of deer-preferred species. We reasoned that tree
      ferns would compete with epiphytic seedlings for light, because below the tree
      fern canopy photosynthetically active radiation (PAR) was about 1% of above
      canopy PAR. Frond removal almost tripled %PAR on the forest floor, leading to a
      significant increase in the height growth rate (HGR) of seedlings planted on the
      forest floor, but having no effects on the HGRs of epiphytic seedlings. Our study
      shows evidence of direct facilitative interactions by tree ferns during seedling
      establishment in plant communities associated with nutrient-rich soils.

PMID- 18049828
TI  - Do secondary compounds inhibit microbial- and insect-mediated leaf breakdown in a
      tropical rainforest stream, Costa Rica?
AB  - We examined the hypothesis that high concentrations of secondary compounds in
      leaf litter of some tropical riparian tree species decrease leaf breakdown by
      inhibiting microbial and insect colonization. We measured leaf breakdown rates,
      chemical changes, bacterial, fungal, and insect biomass on litterbags of eight
      species of common riparian trees incubated in a lowland stream in Costa Rica. The
      eight species spanned a wide range of litter quality due to varying
      concentrations of nutrients, structural and secondary compounds. Leaf breakdown
      rates were fast, ranging from 0.198 d(-1 )(Trema integerrima) to 0.011 d(-1)
      (Zygia longifolia). Processing of individual chemical constituents was also
      rapid: cellulose was processed threefold faster and hemicellulose was processed
      fourfold faster compared to similar studies in temperate streams. Leaf toughness
      (r = -0.86, P = 0.01) and cellulose (r = -0.78, P = 0.02) were the
      physicochemical parameters most strongly correlated with breakdown rate. Contrary
      to our initial hypothesis, secondary compounds were rapidly leached (threefold
      faster than in temperate studies), with all species losing all secondary
      compounds within the first week of incubation. Cellulose was more important than
      secondary compounds in inhibiting breakdown. Levels of fungal and bacterial
      biomass were strongly correlated with breakdown rate (fungi r = 0.64, P = 0.05;
      bacteria r = 0.93, P < 0.001) and changes in structural compounds (lignin r = 
      0.55, P = 0.01). Collector-gatherers were the dominant functional group of
      insects colonizing litterbags, in contrast to temperate studies where insect
      shredders dominate. Insect biomass was negatively correlated with breakdown rate
      (r = -0.70, P = 0.02), suggesting that insects did not play an important role in
      breakdown. Despite a wide range of initial concentrations of secondary compounds
      among the eight species used, we found that secondary compounds were rapidly
      leached and were less important than structural compounds in determining
      breakdown rates.

PMID- 18049830
TI  - Echocardiography in leiomyomatosis of the uterus: how to guide your surgeon.

PMID- 18049831
TI  - Effect of statin therapy on reperfusion arrhythmia in patients who underwent
      successful primary angioplasty.
AB  - BACKGROUND: In animal models, pretreatment with statin can prevent reperfusion
      arrhythmia. In the observational study, we investigated whether pretreatment with
      statin may prevent reperfusion arrhythmia in patients who underwent primary
      coronary intervention for acute myocardial infarction (AMI). METHOD AND RESULTS:
      A total of 226 consecutive patients who underwent successful primary angioplasty
      for a first AMI were studied. Reperfusion arrhythmias were defined as all
      arrhythmias that occurred within 2 h after successful primary angioplasty. The
      reperfusion arrhythmia was found in 130 of 226 patients. There were no
      significant differences in clinical characteristics between the patients with and
      without statin pretreatment. However, the 41 patients receiving statin treatment
      before admission had lower incidence of the reperfusion arrhythmia than those
      without it (19.5% and 65.9%, P < 0.01). Multivariable logistic regression
      analysis revealed that absence of statin pre-treatment was a significant
      predictor of the reperfusion arrhythmia along with absence of pre-infarction
      angina and inferior AMI. CONCLUSION: Pre-treatment with statin could reduce the
      reperfusion arrhythmias after acute myocardial infarction in human.

PMID- 18049832
TI  - Heart rate recovery after exercise is associated with resting QTc interval in
      young men.
AB  - Heart rate recovery (HRR) after exercise and spectral decomposition of heart rate
      variability (HRV), measures of autonomic nervous system function, are predictors
      of cardiovascular morbidity/mortality. QT interval, an index of ventricular
      depolarization and repolarization attained from surface ECG, is also associated
      with morbidity/mortality and is strongly influenced by autonomic tone. The
      purpose of this study was to assess the association between HRR after exercise,
      resting HRV and resting rate corrected QT interval in young healthy men. HRR was
      assessed in 37 men (23.3 +/- 0.6 years) 1 minute after a graded exercise test.
      Resting QT interval was derived from ECG recordings and rate corrected using five
      formulae (Bazett, Fridericia, Hodges, Framingham, and the nomogram method of
      Karjalainen). Resting HRV was spectrally decomposed using an autoregressive
      approach. A negative correlation was detected for QTc interval and HRR for each
      method (r = -0.36 to -0.48, P < 0.05). There was no correlation between high
      frequency power of HRV (a marker of parasympathetic modulation) and QTc interval.
      There was a negative relationship between absolute LF power (a marker of both
      sympathetic and parasympathetic modulation) and QTc interval for Karjalainen,
      Framingham, and Bazett correction methods (r = -0.33 to -0.47, P < 0.05). Resting
      LF power of HRV and HRR after exercise are inversely associated with resting QTc
      interval in young healthy men, supporting a relationship between cardiac
      autonomic nervous system function and ventricular depolarization and
      repolarization.

PMID- 18049833
TI  - Skin autonomic reactivity to thermoalgesic stimuli.
AB  - OBJECTIVE: Quantitative sensory testing (QST) is a subjective method of assessing
      thermal sensation, but it does not provide an objective measure of physiological
      changes. Our aim was to establish whether fluctuations in sudomotor autonomic
      activity correlate with warmth and heat pain (thermoalgesic) perception. METHODS:
      We conducted various thermal stimuli protocols in 22 healthy volunteers and
      recorded the visual analog scale (VAS) and sudomotor activity using surface
      electrodes attached to the hand. Sympathetic skin responses (SSR) and the mean
      level of electrodermal activity (EDA) were measured. EDA was analyzed by looking
      at the four VAS-based phases, which were divided into segments defined by the
      relevant psychophysical markers. RESULTS: In all stimuli paradigms, the mean
      delay time of the SSR was 1.6 s after the warmth or pain sensation. There was an
      association between the low amplitude (predominantly negative) SSR and warm
      stimuli, and the large amplitude (predominantly positive) SSR and heat pain
      stimuli (chi-square; P < 0.05). Mean EDA was significantly higher during the pain
      phase in comparison with pre-perception, warmth and post-perception phases.
      INTEPRETATION: Thermoalgesic stimuli induce reflex changes in sudomotor activity
      that correlate with subjective perception of warmth and heat pain sensations.
      This association may be useful in clinical practice.

PMID- 18049834
TI  - Exercise training improves cardiovascular and autonomic profiles in HIV.
AB  - OBJECTIVES: Human immunodeficiency virus (HIV) is associated with cardiovascular
      (CV) and autonomic dysfunction, however the effects of fitness on vascular and
      autonomic mechanisms in HIV disease are unknown. METHODS: We studied forty-eight
      subjects (40.4 +/- 4.2 years) in a cross-sectional design matched for age,
      gender, BMI, and fitness. Participants were assigned to 1 in 4 groups: 1) Healthy
      Unfit (HU), 2) Healthy Fit (HF), 3) HIV Positive Unfit (HPU), and 4) HIV Positive
      Fit (HPF). Fitness was assessed via open-circuit spirometry; arterial compliance
      and autonomic modulations were measured via applanation tonometry and power
      spectral analysis, respectively, and baroreflex sensitivity was obtained using
      the alpha index. RESULTS: Arterial compliance was augmented in HPF vs. HPU [7.4
      +/- 1.9 mmHg x second vs. 4.4 +/- 1.7 mmHg x second (P = 0.006)]. Parasympathetic
      modulation was higher in HPF vs. HPU [2244.5 +/- 2997.6 msecond(2) vs. 489.1 +/-
      552.9 msecond(2) (P < 0.05)]. Sympathetic modulation was lower in HPF vs. HU [4.7
      +/- 5.0 mmHg(2) vs. 12.9 +/- 9.7 mmHg(2) (P < 0.05)]. Baroreflex sensitivity was
      higher in HPF vs. HPU [17.3 +/- 10.2 msecond/mmHg vs. 7.4 +/- 3.8 msecond/mmHg (P
      = 0.003)], and HPF vs. HU [17.3 +/- 10.2 msecond/mmHg vs. 6.2 +/- 3.0
      msecond/mmHg (P = 0.004)]. CONCLUSIONS: Augmentations in arterial compliance and
      baroreflex sensitivity associated with fitness portent an improved CV and
      autonomic profile for HIV-positive individuals. Physical activity may be an
      adjuvant method to enhance the overall vascular health in HIV-compromised
      individuals.

PMID- 18049835
TI  - Renal artery stump to inferior vena cava fistula: unusual clinical presentation
      and transcatheter embolization with the Amplatzer vascular plug.
AB  - Fistulous communication between the renal artery stump and inferior vena cava
      following nephrectomy is rare. We describe the case of a 52-year-old man with a
      fistula detected on investigation for hemolytic anemia in the postoperative
      period. The patient had had a nephrectomy performed 2 weeks prior to presentation
      for blunt abdominal trauma. The fistula was successfully occluded percutaneously
      using an Amplatzer vascular plug. The patient recovered completely and was
      discharged 2 weeks later.

PMID- 18049836
TI  - Chromosome X modulates incidence of testicular germ cell tumors in Ter mice.
AB  - Germ cell tumor development in humans has been proposed to be part of testicular
      dysgenesis syndrome (TDS), which manifests as undescended testes, sterility,
      hypospadias, and, in extreme cases, as germ cell tumors. Males of the Ter mouse
      strain show interesting parallels to TDS because they either lack germ cells and
      are sterile or develop testicular germ cell tumors. We found that these defects
      in Ter mice are due to mutational inactivation of the Dead-end (Dnd1) gene. Here
      we report that chromosome X modulates germ cell tumor development in Ter mice. We
      tested whether the X or the Y chromosome influences tumor incidence. We used
      chromosome substitution strains to generate two new mouse strains: 129-Ter/Ter
      that carry either a C57BL/6J (B6)-derived chromosome (Chr) X or Y. We found that
      Ter/Ter males with B6-Chr X, but not B6-Chr Y, showed a significant shift in
      propensity from testicular tumor development to sterile testes phenotype. Thus,
      our studies provide unambiguous evidence that genetic factors from Chr X modulate
      the incidence of germ cell tumors in mice with inactivated Dnd1.

PMID- 18049837
TI  - Genotype of bovine sterol regulatory element binding protein-1 (SREBP-1) is
      associated with fatty acid composition in Japanese Black cattle.
AB  - To investigate genetic factors that affect fatty acid composition in beef
      carcass, we previously investigated genetic profiles of stearoyl-CoA desaturase
      (SCD) and their effect on fatty acid composition in fat tissue of cattle. It has
      been known that sterol regulatory element binding protein (SREBP) is a
      transcription factor that regulates gene expression levels of SCD and other genes
      relevant to lipid and fatty acid metabolism in tissue. Therefore, we determined
      the full-length sequence of bovine SREBP-1 cDNA and then surveyed polymorphisms
      in whole exons and introns in the bovine genome. Large 84-bp insertion (long
      type: L) and deletion (short type: S) were found in intron 5 of bovine SREBP-1 in
      Japanese Black cattle, although there was no notable mutation in exon regions.
      The associations between the SREBP-1 genotypes and fatty acid compositions/fat
      melting points were analyzed by using genomic DNA with carcass trait information
      from 606 Japanese Black cattle. The S type contributed to 1.3% higher
      monounsaturated fatty acid (MUFA) proportion and 1.6 degrees C lower melting
      point in intramuscular fat. Genotyping of bovine SREBP-1 is considered to reflect
      a genetic variation which is associated with physiologic characteristics of fat
      tissue in Japanese black cattle.

PMID- 18049838
TI  - Novel repeat polymorphisms of the dopaminergic neurotransmitter genes among dogs
      and wolves.
AB  - Genetic polymorphisms of the neurotransmission systems are intensively studied in
      the human because of a possible influence on personality traits and the risk of
      psychiatric disorders. The investigation of genetic variations of the dog genome
      has recently been a promising approach, as a considerable similarity can be
      observed between dogs and humans, in both genetic and social aspects, suggesting
      that the dog could become an appropriate animal model of human behavioral genetic
      studies. The aim of our study was the identification and analysis of variable
      number of tandem repeats polymorphisms (VNTRs) in the genes of the dopaminergic
      neurotransmitter system of dogs. The in silico search was followed by the
      development of PCR-based techniques for the analysis of the putative VNTRs.
      Highly variable repetitive sequence regions were found in the tyrosine
      hydroxylase (TH), dopamine transporter (DAT), and dopamine beta-hydroxylase (DBH)
      genes. Allele frequency and genotype distribution of these novel polymorphisms
      together with the exon 3 and exon 1 VNTR of the dopamine D4 receptor gene were
      determined in a large sample involving four dog breeds (German Shepherd, Belgian
      Tervueren, Groenandael, and Malinois) and European Grey Wolves. A significant
      difference of allele and genotype frequencies was demonstrated among the analyzed
      breeds; therefore, an association analysis was also carried out between the
      activity-impulsivity phenotype and the described VNTRs. Preliminary findings are
      presented that polymorphisms of the DRD4, DBH, and DAT genes can be associated
      with attention deficit among Belgian Tervuerens.

PMID- 18049839
TI  - Transperineal rectocele repair with polyglycolic acid mesh: a case series.
AB  - PURPOSE: This study was designed to evaluate the outcome of transperineal
      rectocele repair using polyglycolic acid mesh. METHODS: Eighty-three consecutive
      females with predominant, symptomatic Stage II or Stage III rectocele underwent
      transperineal rectocele repair using polyglycolic acid (Soft PGA Felt(R)) mesh
      and finished their six-month follow-up. No additional interventions, including
      levatoroplasty or perineorraphy, were performed. The preoperative and
      postoperative symptom scores and stages of the posterior vaginal wall prolapse
      were recorded. The end points were reassessed at six months, postoperatively.
      RESULTS: Preoperatively, 39 patients had Stage II and 44 patients had Stage III
      rectocele. The mean total symptom score was 9.87 +/- 1.93, which was reduced to
      1.62 +/- 0.59 postoperatively (P < 0.0001). Objective evaluation of anatomic
      repair revealed that 74 patients (89.2 percent) had anatomic cure. Surgical
      complications were seen in a total of seven patients (8.4 percent), including
      hemorrhage (3.6 percent) and wound infection (4.8 percent). Mesh erosion, mesh
      infection, or worsening of sexual function was not noted. CONCLUSIONS:
      Transperineal repair of rectocele with the polyglycolic acid mesh is an efficient
      therapy for patients with rectocele. It is highly successful in eliminating
      symptoms of obstructed defecation, and it is free of significant complications.

PMID- 18049840
TI  - Pancreatic cancer cell genetics and signaling response to treatment correlate
      with efficacy of gemcitabine-based molecular targeting strategies.
AB  - INTRODUCTION: Pancreatic cancer is a deadly cancer with limited sensitivity to
      gemcitabine. Molecular targeting of critical signaling pathways [nuclear factor
      kappa-B (NF-kappaB), PI3K/AKT, and mitogen-activated protein kinase (MAPK)] in
      combination with gemcitabine may improve sensitivity. We hypothesize that
      pancreatic cancer cell genetics and signaling response to treatment correlate
      with efficacy of gemcitabine-based molecular targeting strategies. MATERIALS AND
      METHODS: PANC-1, PaCa-2, and BxPC-3 cells were treated with curcumin, LY294002,
      or PD325901 alone or in combination with gemcitabine. Proliferation was measured
      by cell counts and enzyme activity by Western blot and electrophoretic mobility
      shift assay. RESULTS: Each agent dose-dependently decreased proliferation. All
      cells decreased NF-kappaB activity with curcumin(24 h) except PaCa-2, MEK
      activity with PD325901(24 h), and PI3Kinase with LY294002(3 h). However, PI3K
      rebounded to(PaCa-2) or above (Panc-1,BxPC-3) basal in LY294002-treated cells (24
      h). Combinations with gemcitabine resulted in at least additive effects on
      proliferative inhibition. For PANC-1, curcumin + gemcitabine was nearly
      synergistic, correlating with gemcitabine-induced NF-kappaB activity. LY294002 +
      gemcitabine was nearly synergistic in PaCa-2 cells, which showed a lower
      induction of PI3Kinase activity with LY294002. Finally, gemcitabine + PD325901
      was only effective in BxPC-3, which exhibited increased MEK activity with
      gemcitabine. CONCLUSIONS: These results demonstrate differences in treatment
      efficacy, which correlate with the cell's signaling response to treatment.
      Signaling profiles of each tumor may be necessary to determine an optimal
      chemotherapy for pancreatic cancer.

PMID- 18049842
TI  - Gender differences in early outcomes following hand-assisted laparoscopic Roux-en
      Y gastric bypass surgery : gender differences in bariatric surgery.
AB  - BACKGROUND: Male gender has been associated with a higher morbidity and mortality
      rate after bariatric surgery including laparoscopic and open procedures. This
      study focused on hand-assisted laparoscopic Roux-en-Y gastric bypass and
      morbidity and mortality among genders. METHODS: Hand-assisted laparoscopic Roux
      en-Y gastric bypass operations (N = 319) were evaluated from October 2003 to
      March 2006. Comparison between males (N = 54) and females (N = 265) were
      conducted using t test or Fishers exact test and chi-square analysis. RESULTS:
      Patients' average age was 42.3 +/- 10.3 and the average body mass index (BMI) was
      49.2 +/- 7.9. There was no significant difference between males and females in
      age or BMI. Males had a significantly greater average weight than females (p <
      0.001) and were significantly more likely to experience sleep apnea (p = 0.006)
      and have heart disease (p = 0.017). For operative risk factors, males had a
      significantly longer anesthesia time (p = 0.003), operative time (p = 0.027), and
      length of roux limb (p = 0.038). At 6 and 12 months postsurgery, there was no
      significant difference between males and females with complications. Although BMI
      did not differ significantly, males continued to weigh significantly more than
      females and lost significantly more pounds than did females at both 6 and 12
      months postoperation. CONCLUSION: Given their larger size and tendency to
      accumulate fat in the abdominal compartment that increases the technical
      difficulty of the procedure, males are historically associated with a higher
      morbidity and mortality following bariatric surgery. Based on the current study,
      however, there is no difference in outcome among genders following hand-assisted
      laparoscopic Roux-en-Y gastric bypass.

PMID- 18049841
TI  - Increase in ghrelin levels after weight loss in obese Zucker rats is prevented by
      gastric banding.
AB  - BACKGROUND: Gastric banding is thought to decrease appetite in addition to the
      mechanical effects of food restriction, although this has been difficult to
      demonstrate in human studies. Our aim was to investigate the changes in
      orexigenic signals in the obese Zucker rat after gastric banding. METHODS: Obese
      Zucker rats (fa/fa) were submitted to gastric banding (GBP), sham gastric banding
      fed ad libitum (sham), or sham operation with food restriction, pair-fed to the
      gastric banding group (sham-PF). Lean Zucker rats (fa/+) were used as additional
      controls. Body weight and food intake were daily recorded for 21 days after
      surgery when epididymal fat was weighed and fasting ghrelin and hypothalamic NPY
      mRNA expression were measured. RESULTS: Gastric banding in obese Zucker rats
      resulted in a significant decrease of cumulative body weight gain and food
      intake. Furthermore, gastric banded rats were leaner than Sham-PF, as expressed
      by a significantly lower epididymal fat weight. Ghrelin levels of gastric banded
      rats were not increased when compared to sham-operated animals fed ad libitum and
      were significantly lower than the levels of weight matched sham-PF rats (1116.9
      +/- 103.3 g GBP vs 963.2 +/- 54.3 g sham, 3,079.5 +/- 221.6 sham-PF and 2,969.9
      +/- 150.9 g lean rats, p < 0.001); hypothalamic NPY mRNA expression was not
      increased in GBP when compared to sham-operated rats. CONCLUSION: In obese Zucker
      rats, GBP prevents the increase in orexigenic signals that occur during caloric
      deprivation. Our data support the hypothesis that sustained weight loss observed
      after gastric banding does not depend solely on food restriction.

PMID- 18049851
TI  - Feasibility of the fast-track recovery program after cardiac surgery in Japan.
AB  - OBJECTIVES: The purpose of this study was to determine if a fast-track recovery
      protocol that is applied in other countries can be used in the present Japanese
      medical system. Second, we wanted to evaluate the differences if the protocol was
      adapted from the viewpoint of cost saving, postoperative hospital stay, and
      adverse complications. METHODS: We retrospectively analyzed 94 consecutive
      patients who underwent cardiovascular surgery with conventional techniques on
      cardiac arrest requiring cardiopulmonary bypass between July 1, 2004 and June 30,
      2006. We started our fast-track recovery protocol from July 1, 2005. We compared
      the results of the conventional group (before July 1, 2005) and the fast-track
      recovery protocol group (after July 1, 2005). Moreover, we used a unique
      questionnaire and investigated how the patients in the fast-track group felt
      about the short hospital stay postoperatively. RESULTS: The mean postoperative
      hospital stay was 36.7 +/- 6.0 days for the conventional group and 15.0 +/- 12.4
      days for the fast-track group, with a statistically significant difference (P =
      0.01). The mean cost fell by almost half, from 712545 yen to 383268 yen (P =
      0.038). The difference in complication rates was not statistically significant.
      CONCLUSION: A fast-track recovery protocol can be safely adapted to patients in
      the Japanese system without increasing the mortality or morbidity rate. Based on
      our unique questionnaires, the most important factor was sufficient and repeated
      explanations preoperatively to the patients and their family members. Second,
      good pain control with routine use of acetaminophen and sporadic morphine orally
      has a great effect on the patients' recovery.

PMID- 18049852
TI  - Barium-enhanced imaging of the coronary vasculature of the porcine myocardium:
      empirical investigation into the theory of the ventricular myocardial band.
AB  - OBJECTIVE: The ventricular myocardium is thought to exist as a single continuous
      muscle band that extends from the pulmonary artery to the aorta, wrapped into a
      double helical coil Torrent-Guasp's theory of the ventricular myocardial band
      (VMB). The purpose of this study was to examine the coronary blood supply to the
      VMB and to evaluate the effect of coronary blood systems on structure-function
      relations in the myocardium. METHODS: VMBs of nine swine hearts were unwrapped
      after postmortem barium coronary angiography. Unwrapped VMBs underwent
      radiography, and vascular images of barium remaining in the VMBs were evaluated.
      RESULTS: We were able to achieve a single longitudinal and stretched myocardial
      band in all nine porcine hearts. The corresponding regions supplied by each
      coronary artery were clearly distinguishable in the VMBs. The right segment of
      the basal loop was supplied by the right coronary artery. The left segment of the
      basal loop was supplied by the left circumflex artery. Most of the descending
      segment of the apical loop was supplied by the left anterior descending artery,
      with an inferior portion supplied by the right coronary artery. Most of the
      ascending segment of the apical loop was supplied by the left anterior descending
      artery, with a posterior portion supplied by the left circumflex artery.
      CONCLUSION: Understanding the trinity of structure, function, and coronary blood
      supply from the viewpoint of the VMB should facilitate development of more
      effective surgical treatment for severe ischemic heart disease.

PMID- 18049853
TI  - Pulmonary metastasis from colorectal carcinoma with hepatic metastasis.
AB  - OBJECTIVE: Although some beneficial effects of surgical treatments for pulmonary
      or hepatic metastases from colorectal carcinoma have been reported, identifying
      candidates for these aggressive surgical procedures is controversial. In this
      study, patients with pulmonary metastases from colorectal carcinoma, particularly
      those with pulmonary and hepatic metastases, were retrospectively analyzed.
      METHODS: Forty-six patients who had undergone complete resection for pulmonary
      metastases from colorectal carcinoma were retrospectively analyzed. RESULTS: The
      median follow-up period after pulmonary resection was 26 months, and the 5-year
      postoperative survival rate was 34%. The 5- and 10-year survival rates of
      patients with pulmonary metastasis alone, metachronous pulmonary metastasis after
      liver metastasis, and synchronous metastasis to the liver and lung were 75%, 75%,
      and 25% and 25%, 38%, and 0%, respectively, when calculated from the time of
      primary colorectal resection (P < 0.01). Patients with synchronous metastases had
      a poorer prognosis than did the patients in the other two groups. CONCLUSIONS:
      Surgical treatments for patients with pulmonary metastasis alone or metachronous
      metastasis can provide a beneficial outcome. Patients with synchronous metastasis
      have a poor prognosis, and effective pre- and postoperative systemic treatments
      should be considered to prolong their survival.

PMID- 18049854
TI  - Salvage esophagectomy following definitive chemoradiotherapy.
AB  - OBJECTIVES: To evaluate the outcome of salvage surgery following definitive
      chemoradiotherapy (CRT) for locally advanced esophageal cancer. METHODS: We
      reviewed patients undergoing salvage esophagectomy from August 2000 through April
      2006 at the National Cancer Center Hospital East, following 5-fluorouracil and
      cisplatinum chemotherapy with concurrent radiotherapy over 50 Gy.
      Clinicopathological backgrounds, complications, and survival were analyzed.
      RESULTS: Forty-six patients (42 men, all with squamous cell carcinoma) underwent
      salvage surgery after full-dose concurrent chemoradiotherapy. The median age was
      61 years (range, 43-72). Thirteen patients had a relapse after complete response;
      26 patients partial response; 4 patients progressive disease; 3 patients NC to
      CRT. Salvage surgery consisted of transthoracic esophagectomy, three-field node
      dissection, and reconstruction with the colon or stomach with vascular
      restoration. Operation time ranged from 257 to 602 min. Postoperative
      complications were pneumonia in 5; anastmotic leakage in 10; wound infection in
      3; anastomotic stenosis in 2; recurrent nerve palsy in 4; pyothorax in 2;
      multiple organ failure in 1; myocardial infarction in 1; trachea necrosis in 1.
      There were four 30-day operative deaths and three more hospital deaths. The
      median survival time from salvage surgery was 12 months and that from CRT was 22
      months. The 3-year survival rate was 17%. Three patients are surviving more than
      3 years and their diseases were pathological NO. CONCLUSION: Mobidity and
      mortality rates were high among patients undergoing salvage esophagectomy.
      However, there are some long-term survivors, and highly selected patients should
      be indicated for salvage surgery.

PMID- 18049855
TI  - Neurally mediated syncope after thoracic surgery diagnosed in the intensive care
      unit.
AB  - We report a postoperative patient who developed neurally mediated syncope, which
      was diagnosed using head-up tilt testing after the patient developed syncope in
      the intensive care unit. The patient had been misdiagnosed as having epilepsy
      since her childhood. Therefore, in patients with presumed epilepsy who present
      with syncope and have a nondiagnostic electroencephalogram, cardiac causes of
      syncope, such as neurally mediated syncope, should be considered.

PMID- 18049856
TI  - Pulmonary Paragonimus westermani with false-positive fluorodeoxyglucose positron
      emission tomography mimicking primary lung cancer.
AB  - We report the case of a 66-year-old woman with pulmonary Paragoniumus westermani
      showing false-positive fluorodeoxyglucose positron emission tomograpy (FDG-PET).
      Based on chest computed tomography and FDG-PET findings, we could not rule out
      the possibility of primary lung cancer. She underwent right middle and lower
      lobectomies as a primary lung cancer. As a possibility in the differential
      diagnosis of a pulmonary nodule with FDG-PET positive findings, paragonimiasis
      should be considered, although it is rarely seen.

PMID- 18049857
TI  - Total arch replacement through re-median sternotomy after coronary surgery.
AB  - We report the case of 78-year-old-man who required graft replacement of an aortic
      arch aneurysm. He previously had undergone off-pump coronary artery bypass
      grafting with the right internal thoracic artery bypassed to the left anterior
      descending artery. For this difficult case, we successfully performed total arch
      replacement using selective antegrade cerebral perfusion through a re-median
      sternotomy without injuring the right internal thoracic artery, which was the
      only blood source for the left and right coronary arteries.

PMID- 18049858
TI  - Bronchopulmonary foregut malformation in an adult.
AB  - A 50-year-old man with repeated episodes of right epigastric pain was seen in our
      hospital. Chest computed tomography and angiography revealed several arteries
      feeding an enhanced large mass located in the right lower lobe region. A right
      lower lobectomy was done with a provisional diagnosis of an intralobar
      sequestration. A 5-mm duct that was lined with esophageal mucous membrane that
      tracked from the lower esophagus toward the sequestrated lung was detected. A
      bronchopulmonary foregut malformation (BPFM) was diagnosed based on the
      histological finding that the duct was composed of ciliated epithelium and smooth
      muscle layers. BPFM is a subgroup of pulmonary sequestrations that communicate
      with the gastrointestinal tract. In contrast to pulmonary sequestrations, 75% of
      BPFMs are located on the right side. Thus, a BPFM should be considered in
      patients with right-sided pulmonary sequestrations, and their gastrointestinal
      tracts should be examined.

PMID- 18049859
TI  - N-acetylmuramic acid 6-phosphate lyases (MurNAc etherases): role in cell wall
      metabolism, distribution, structure, and mechanism.
AB  - MurNAc etherases cleave the unique D-lactyl ether bond of the bacterial cell wall
      sugar N-acetylmuramic acid (MurNAc). Members of this newly discovered family of
      enzymes are widely distributed among bacteria and are required to utilize
      peptidoglycan fragments obtained either from the environment or from the
      endogenous cell wall (i.e., recycling). MurNAc etherases are strictly dependent
      on the substrate MurNAc possessing a free reducing end and a phosphoryl group at
      C6. They carry a single conserved sugar phosphate isomerase/sugar phosphate
      binding (SIS) domain to which MurNAc 6-phosphate is bound. Two subunits form an
      enzymatically active homodimer that structurally resembles the isomerase module
      of the double-SIS domain protein GlmS, the glucosamine 6-phosphate synthase.
      Structural comparison provides insights into the two-step lyase-type reaction
      mechanism of MurNAc etherases: beta-elimination of the D-lactic acid substituent
      proceeds through a 2,3-unsaturated sugar intermediate to which water is
      subsequently added.

PMID- 18049861
TI  - An evaluation study of trace element content in colorectal liver metastases and
      surrounding normal livers by X-ray fluorescence.
AB  - BACKGROUND: Trace elements are involved in many key pathways involving cell cycle
      control. The levels of trace metals such as iron, copper, and zinc in colorectal
      liver metastases have not previously been assessed. METHODS: The trace element
      content in snap-frozen cancerous liver tissue from patients who underwent liver
      resection for colorectal liver metastases was compared with the normal
      surrounding liver (distant from the cancer) using X-ray fluorescence (XRF).
      RESULTS: X-ray fluorescence was performed on a total of 60 samples from 30
      patients. Of these 29 matched pairs (of cancer and normal liver distant from
      cancer from the same patient) were eligible for univariate analysis. Iron
      (0.00598 vs. 0.02306), copper (0.00541 vs. 0.00786) and zinc (0.01790 vs.
      0.04873) were statistically significantly lower in the cancer tissue than the
      normal liver. Iron, copper, and zinc were lower in the cancer tissue than in the
      normal liver in 24/29 (82.8%), 23/29 (79.3%), and 28/29 (96.6%) of cases
      respectively. Multivariate analysis of the 60 samples revealed that zinc was the
      only trace element decreased in the cancer tissue after adjusting for the other
      elements. Zinc levels were not affected by any of the histopathological
      variables. CONCLUSION: Iron, copper, and zinc are lower in colorectal liver
      metastases than normal liver. An investigation into the pathways underlying these
      differences may provide a new understanding of cancer development and possible
      novel therapeutic targets.

PMID- 18049860
TI  - Darier's disease: a calcium-signaling perspective.
AB  - Ca(2+) influx evoked across the plasma membrane upon internal store depletion is
      essential for a myriad of cellular functions including gene expression, cell
      proliferation, differentiation and even apoptosis. Darier's disease (DD), an
      autosomal dominant inherited disorder of the skin, arising due to mutations in
      the isoform 2 of the sarco (endo) plasmic reticulum Ca(2+) ATPase (SERCA2),
      exemplifies an anomaly of Ca(2+) signaling disturbances. Owing to loss of
      function mutations in SERCA2, keratinocytes in DD patients have a reduced pool of
      endoplasmic reticulum (ER) Ca(2+). Importantly, the status of ER Ca(2+) is
      critical for the activation of a class of plasma membrane Ca(2+) channels
      referred to as store operated Ca(2+) channels (SOCs). The widely expressed
      transient receptor potential (TRP) family of channels is proposed to be SOCs. In
      this review we discuss DD from the viewpoint of Ca(2+) signaling and present a
      potential role for TRPC1 in the disease pathogenesis.

PMID- 18049862
TI  - Using metastasis suppressor proteins to dissect interactions among cancer cells
      and their microenvironment.
AB  - Cancer metastasis is a complex, dynamic process that begins with dissemination of
      cells from the primary tumor and culminates in the formation of clinically
      detectable, overt metastases at one or more discontinuous secondary sites.
      Evidence from in vivo video microscopy as well as PCR and immunohistochemical
      studies suggest that cancer cell dissemination is an early event in tumor
      progression and that cells may persist in a potentially dormant state for a
      prolonged period. Similarly, the mechanisms by which these disseminated cells
      initiate growth and complete the process of metastatic colonization remain
      largely unknown. Understanding signal transduction pathways regulating this final
      step of metastasis is therefore critical for successful clinical management.
      While genetic mutations or epigenetic changes may be required for a cell or group
      of cells to separate and survive distant from the primary tumor, the
      microenvironment within secondary tissues plays a substantial role in influencing
      whether disseminated cells survive and proliferate. Our work is focused on using
      metastasis suppressor proteins to gain insight into why the majority of
      disseminated cells, which should be fully malignant, do not proliferate
      immediately at secondary sites. The translational goal of this work is to
      identify targets for inhibiting metastatic growth and prolonging disease-free
      survival.

PMID- 18049863
TI  - Osteopontin: regulation in tumor metastasis.
AB  - Osteopontin is a secreted phosphoprotein that has been implicated as an important
      mediator of tumor metastasis and has been investigated for use as a biomarker for
      advanced disease and as a potential therapeutic target in the regulation of
      cancer metastasis. The OPN DNA sequence is highly conserved and the protein
      contains several important functional domains including alpha(v)beta integrin and
      CD44 binding sites. High levels of OPN expression correlate with tumor invasion,
      progression or metastasis in multiple cancer. Studies demonstrate that
      osteopontin mediates the molecular mechanisms which determine metastatic spread,
      such as prevention of apoptosis, extracellular matrix proteolysis and remodeling,
      cell migration, evasion of host-immune cells and neovascularization.
      Transcriptional regulation of OPN is complex and involves multiple pathways,
      including AP-1, Myc, v-Src, Runx/CBF, TGF-B/BMPs/Smad/Hox, and Wnt/ss
      catenin/APC/GSK-3ss/Tcf-4. The current state of knowledge of OPN biology suggests
      that it is an attractive target for therapeutic modulation of metastatic disease.

PMID- 18049864
TI  - Effect of siRNA targeted against MKK4 on myostatin-induced downregulation of
      differentiation marker gene expression.
AB  - The c-Jun N-terminal kinase (JNK) pathway was reported to be involved in
      myostatin signaling and MKK4 was suggested as the only upstream kinase for
      myostatin-induced JNK activation, implying that MKK4 is a suitable target of RNA
      interference (RNAi) for blocking myostatin activity. The aim of this study was to
      evaluate the effect of small interfering RNA (siRNA) targeted against MKK4 on
      myostatin-induced downregulation of differentiation marker gene expression. Real
      time quantitative PCR revealed that the level of MKK4 expression was efficiently
      reduced by MKK4-specific siRNA. Western blot assays showed that knockdown of MKK4
      attenuated the myostatin-induced downregulation of MyoD and myogenin expression.

PMID- 18049865
TI  - Secretory cargo composition affects polarized secretion in MDCK epithelial cells.
AB  - Polarized epithelial cells secrete proteins at either the apical or basolateral
      cell surface. A number of non-epithelial secretory proteins also exhibit
      polarized secretion when they are expressed in polarized epithelial cells but it
      is difficult to predict where foreign proteins will be secreted in epithelial
      cells. The question is of interest since secretory epithelia are considered as
      target tissues for gene therapy protocols that aim to express therapeutic
      secretory proteins. In the parathyroid gland, parathyroid hormone is processed by
      furin and co-stored with chromogranin A in secretory granules. To test the
      secretion of these proteins in epithelial cells, they were expressed in MDCK
      cells. Chromogranin A and a secreted form of furin were secreted apically while
      parathyroid hormone was secreted 60% basolaterally. However, in the presence of
      chromogranin A, the secretion of parathyroid hormone was 65% apical, suggesting
      that chromogranin can act as a "sorting escort" (sorting chaperone) for
      parathyroid hormone. Conversely, apically secreted furin did not affect the
      sorting of parathyroid hormone. The apical secretion of chromogranin A was
      dependent on cholesterol, suggesting that this protein uses an established
      cellular sorting mechanism for apical secretion. However, this sorting does not
      involve the N-terminal membrane-binding domain of chromogranin A. These results
      suggest that foreign secretory proteins can be used as "sorting escorts" to
      direct secretory proteins to the apical secretory pathway without altering the
      primary structure of the secreted protein. Such a system may be of use in the
      targeted expression of secretory proteins from epithelial cells.

PMID- 18049866
TI  - Effect of SPLUNC1 protein on the Pseudomonas aeruginosa and Epstein-Barr virus.
AB  - Short palate, lung and nasal epithelium clone 1 (SPLUNC1) gene coded a secreted
      protein found at the surface of nasopharyngeal epithelium, which may be an innate
      immunity defensive molecular and a risk factor for nasopharyngeal carcinoma
      (NPC). Here, we observed the effects of SPLUNC1 on the Gram negative bacteria
      Pseudomonas aeruginosa, evaluated the ability of SPLUNC1 protein binding to
      lipopolysaccharide. To observe the effect of SPLUNC1 protein on Epstein-Barr
      virus (EBV), we raised three EBV-transformed B-lymphocyte lines and treated the
      cells by SPLUNC1 protein; cellular disruption, apoptosis, EBV DNA content, and
      viral oncogene expression were analyzed. We found that SPLUNC1 protein can bind
      to bacterial lipopolysaccharide, inhibit the growth of P. aeruginosa, enhance the
      disruption and apoptosis of EBV-infected B-lymphocytes, downregulate protein
      expression of EBV latent membrane protein 1, while upregulate protein expression
      of EBV envelope glycoprotein gp350/220. The total EBV DNA in the culture medium
      was decreased significantly after 7 days of treatment by SPLUNC1. This study
      shows that SPLUNC1 not only has the role of antibacteria and antivirus, but also
      inhibits the potential oncogenicity of EBV in respiratory epithelium.

PMID- 18049867
TI  - Pitx3 promoter directs Cre-recombinase specifically in a human neuroblastoma cell
      line.
AB  - The Pitx3 gene is a homeobox transcription factor. This gene is expressed only in
      midbrain dopaminergic-neurons in the central nervous system, where its expression
      is important for development and survival of mesencephalic-dopaminergic neurons.
      The promoter region of the Pitx3 gene is not yet completely delimited. We used
      the Cre-loxP system to demonstrate the efficiency and specificity of a 4.2-kbp
      sequence in the 5'-flanking region of the Pitx3-gene promoter inserted in the 5'
      terminus of the Cre-recombinase gene. A Cre-recombinase-reporter assay indicated
      that this 5'-flanking region possesses promoter activity. The cell-specific gene
      regulation of the Pitx3 promoter in neurons was demonstrated by a reverse
      transcription polymerase chain reaction (RT-PCR) and Western blot detection of
      Cre-recombinase in SH-SY5Y cells but not in MCF7 cells. Functionality of the Cre
      recombinase was confirmed in vitro. The Pitx3-promoter-Cre cassette here
      described can be used to develop transgenic mice with the specific expression of
      Cre-recombinase in midbrain-dopaminergic neurons to elucidate the gene function
      in which the conventional knockout leads to an early lethal phenotype. Such
      specific expression of the Pitx3 promoter may be used for gene therapy studies of
      Parkinson's disease.

PMID- 18049868
TI  - The effect of maternal and cord-blood vitamin C, vitamin E and lipid peroxide
      levels on newborn birth weight.
AB  - Background Newborn birth weight has been shown to significantly correlate with
      the blood levels of vitamin C. Objective This study was planned to answer the
      question of why vitamin C levels correlate with birth weight; does such
      correlation reflect a protective effect of vitamin C on fetal growth, by its
      antioxidant characteristics or does it correspond to the nutritional status of
      both the mother and the fetus. We examined the hypothesis that maternal blood
      levels of vitamin C, but not vitamin E influence newborn birth weight. We
      determined maternal and newborn blood levels of vitamin C, vitamin E, and lipid
      peroxides (an index of oxidative insult) and the birth weights of full-term
      newborns delivered at our hospital. Results Compared with maternal blood levels,
      newborns have higher levels of vitamin C and lipid peroxides, but lower levels of
      vitamin E. There was a significant correlation in levels between mothers and
      their newborns for blood levels of vitamin C (r = 0.82, P < 0.01) and vitamin E
      (r = 0.61, P < 0.02) but not for lipid peroxides (r = 0.001). This suggests that
      maternal vitamin C and vitamin E intake can influence fetal vitamin C and vitamin
      E levels. Linear regression analysis shows a significant positive relationship
      between newborn birth weight and maternal plasma vitamin C (r = 0.51, P < 0.02).
      Similarly, there was a modest but significant positive relationship between
      newborn birth weights and newborn vitamin C levels (r = 0.61, P < 0.05). However,
      there was no relationship between maternal or fetal vitamin E or lipid peroxides
      levels and the newborn birth weight. Conclusions This study with a small number
      of subjects suggests a significant association between newborn birth weight and
      maternal and newborn plasma vitamin C levels. Lack of relationship between birth
      weight and vitamin E and lipid peroxides suggest that antioxidant function of
      vitamin C does not appear to have a major role in the effect of vitamin C on
      birth weight.

PMID- 18049869
TI  - Preparation of porous apatite granules from calcium phosphate cement.
AB  - A versatile method for preparing spherical, micro- and macroporous (micro: 2-10
      and macro: 150-550 microm pores), carbonated apatitic calcium phosphate (Ap-CaP)
      granules (2-4 mm in size) was developed by using NaCl crystals as the porogen.
      The entire granule production was performed between 21 and 37 degrees C. A CaP
      cement powder, comprising alpha-Ca3(PO4)2 (61 wt.%), CaHPO4 (26%), CaCO3 (10%)
      and precipitated hydroxyapatite, Ca10(PO4)6(OH)2 (3%), was dry mixed with NaCl
      crystals varying in size from 420 microm to 1 mm. Cement powder (35 wt.%) and
      NaCl (65 wt.%) mixture was kneaded with an ethanol-Na2HPO4 initiator solution,
      and the formed dough was immediately agitated on an automatic sieve shaker for a
      few minutes to produce the spherical granules. Embedded NaCl crystals were then
      leached out of the granules by soaking them in deionized water. CaP granules were
      micro- and macroporous with a total porosity of 50% or more. Granules were
      composed of carbonated, poorly crystallized, apatitic CaP phase. These were the
      first spherical and porous CaP granules ever produced from a self-setting calcium
      phosphate cement. The granules reached their final handling strength at the
      ambient temperature through the cement setting reaction, without having a need
      for sintering.

PMID- 18049870
TI  - Nanoscale surface topography enhances cell adhesion and gene expression of madine
      darby canine kidney cells.
AB  - Substrate topography is one of the key factors that influence cell behavior, such
      as cell attachment, adhesion, proliferation and differentiation. In the present
      work, nanostructures were produced on polystyrene Petri dish by polarized laser
      irradiation with the wavelength of 266 nm and the energy of 3.0 mJ/cm2. Cell
      adhesion, growth and gene expression of Madine darby canine kidney (MDCK) cells
      cultured on smooth and nanogrooved substrates were investigated. The results
      indicated that cells preferred to adhere and grow on nanogrooved substrate. The
      distribution of cell cycle for cells on smooth substrates was different from that
      on nanogrooved substrate. The percentage of G1 phase cells on nanogrooved
      substrate (48.6 +/- 1.4%) was lower than that on smooth substrate (57.6 +/-
      4.4%), while the percentage of cells on nanogrooved substrate in S (30.2 +/-
      0.5%) and G2/M (21.2 +/- 1.1%) phase was higher than those on smooth substrate
      (25.1 +/- 1.5% and 17.3 +/- 3.3%, respectively). Moreover, the gene expression of
      cyclin D1 and keratin 18, which was examined by semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR), was significantly enhanced by
      nanogrooves, with an increase of cyclin D1 mRNA by 98% and an increase of keratin
      18 mRNA by 75%. In conclusion, the nanogrooved surface features on polystyrene
      could alter cell cycle and enhance gene expression of cyclin D1 and keratin 18 in
      MDCK cells, which partly explained the increased cell adhesion and growth on
      nanogrooved substrate.

PMID- 18049871
TI  - Plasma polymerized n-butyl methacrylate coating with potential for re
      endothelialization of intravascular stent devices.
AB  - Rapid re-endothelialization at an atherosclerotic lesion after stent employment
      is essential for reducing or preventing local thrombus formation and restenosis.
      To prevent these complications via enhanced rapid re-endothelialization, poly n
      butyl methacrylate (PPBMA) coating was deposited on the stent surface through a
      radio-frequency plasma polymerization process, with oxygen as the carrier gas.
      Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron
      spectroscopy (XPS) characterization confirmed the occurrence of the plasma
      polymerization and the chemistry properties of the PPBMA. Scanning electron
      microscopy (SEM) revealed a smooth and dense surface. The wettability of the
      polymeric films measured by the contact angle indicated that the surface was more
      hydrophilic (2.0 +/- 1 degrees ) than the original surface (24 +/- 1 degrees ) by
      the introduction of the PPBMA coating, with a slight decrease even after 4 days.
      The results of the culture of human umbilical cord veins endothelial cells
      (HUVEC) in vitro showed that compared with the control of 316L stainless steel,
      the attachment and growth of cells on the PPBMA-coated surface was significantly
      enhanced, and a confluent endothelial cells layer was formed after a 4-day
      culture. A platelet adhesion experiment revealed that the blood compatibility of
      the substrate surface after PPBMA deposition was also obviously improved. The
      PPBMA coating remained intact on the stent surface after expansion according to
      the clinic protocol, indicating that the adhesive strength of PPBMA coating was
      high enough to withstand the external force in the process of stent expansion.
      This in vitro pilot study prior to in vivo experiments suggested that this plasma
      PPBMA was promising for coating stent materials for rapid re-endothelialization.

PMID- 18049872
TI  - Evaluation of the biocompatibility of a new vascular prosthesis coating by
      detection of prosthesis-specific antibodies.
AB  - In recent experimental studies, we could demonstrate the occurrence of antibodies
      against the prosthesis matrix and coating following implantation of polyester
      based vascular grafts. Therefore, this study aimed at evaluating the
      biocompatibility of a new absorbable polymer coating by detection of antibodies
      against the coating and the polyester matrix. Two polyester vascular prostheses
      coated either with the polymer (PP-prosthesis) or with gelatine (PG-prosthesis)
      were functionally implanted into sheep (n = 22 per group). Blood was drawn on
      days 1 (pre-OP) and 7, 14, 28, 56, 84, 140 (post-OP). Homogenates from both
      prostheses (PP-target or PG-target) or from an uncoated prosthesis (P-target)
      were used as assay targets in a particle-based immunoassay. The antibody binding
      against the P-target was significantly higher in the PP-group than in the PG
      group on days 7-56, but not on days 84 and 140. Within both groups, no
      significant differences but a significant correlation between the binding against
      the P-target and the coated target was found. Therefore, the absorbable polymer
      did not induce a specific humoral immune response. In conclusion, the overall
      immunogenicity of the polymer-coated graft was comparable to the gelatine-coated
      graft. The detection of prosthesis-specific antibodies seems to be useful for in
      vivo biocompatibility testing.

PMID- 18049873
TI  - Effect of hot water and heat treatment on the apatite-forming ability of titania
      films formed on titanium metal via anodic oxidation in acetic acid solutions.
AB  - Titanium and its alloys have been widely used for orthopedic implants because of
      their good biocompatibility. We have previously shown that the crystalline
      titania layers formed on the surface of titanium metal via anodic oxidation can
      induce apatite formation in simulated body fluid, whereas amorphous titania
      layers do not possess apatite-forming ability. In this study, hot water and heat
      treatments were applied to transform the titania layers from an amorphous
      structure into a crystalline structure after titanium metal had been anodized in
      acetic acid solution. The apatite-forming ability of titania layers subjected to
      the above treatments in simulated body fluid was investigated. The XRD and SEM
      results indicated hot water and/or heat treatment could greatly transform the
      crystal structure of titania layers from an amorphous structure into anatase, or
      a mixture of anatase and rutile. The abundance of Ti-OH groups formed by hot
      water treatment could contribute to apatite formation on the surface of titanium
      metals, and subsequent heat treatment would enhance the bond strength between the
      apatite layers and the titanium substrates. Thus, bioactive titanium metals could
      be prepared via anodic oxidation and subsequent hot water and heat treatment that
      would be suitable for applications under load-bearing conditions.

PMID- 18049874
TI  - Bioactivity of wollastonite/aerogels composites obtained from a TEOS-MTES matrix.
AB  - Organic-inorganic hybrid materials were synthesized by controlled hydrolysis of
      tetraethoxysilane (TEOS), methyltrimethoxysilane (MTES), synthetic wollastonite
      powders and polydimethylsiloxane (PDMS) in an ethanol solution. Aerogels were
      prepared from acid hydrolysis of TEOS and MTES with different volume ratio in
      ethanol, followed by addition of wollastonite powder and PDMS in order to obtain
      aerogels with 20 wt% of PDMS and 5 wt% of CaO of the total silica. Finally, when
      the wet gels were obtained, they were supercritically dried at 260 degrees C and
      90 bar, in ethanol. In order to obtain its bioactivity, one method for surface
      activation is based on a wet chemical alkaline treatment. The particular interest
      of this study is that we introduce hybrid aerogels, in a 1 M solution of NaOH,
      for 30 s at room temperature. We evaluate the bioactivity of TEOS-MTES aerogel
      when immersed in a static volume of simulated body fluid (SBF). An apatite layer
      of spherical-shaped particles of uniform size smaller than 5 microns is observed
      to form on the surface of the aerogels after 25 days soaking in SBF.

PMID- 18049875
TI  - Porous calcium phosphate ceramic granules and their behaviour in differently
      loaded areas of skeleton.
AB  - Two kinds of calcium phosphate ceramic (CPC) granules of high porosity (50 +/-
      5%) and improved (for such materials) compressive strength (10-25 MPa) consisted
      of hydroxyapatite (PHA) and a mixture of hydroxyapatite (HA) and beta-tricalcium
      phosphate (beta-TCP) in 60 HA/40 beta-TCP composition (PCPC) were developed. A
      comparative study of in vivo behavior of the materials implanted into an almost
      unloaded (greater trochanter of femur) and loaded (distal methaphysis of femur)
      zones in the skeleton of rabbits was performed. Significant activating influence
      of loading on the processes of new bone formation and reconstruction in
      macropores of both materials during all periods of implantation (up to 6 months)
      was observed. The role of relevant cells in the processes in the unsoluble PHA
      and the degradable PCPC (in which the processes was observed to intensify due to
      dissolution of the material) was studied and is discussed. Great disturbance in
      pore structure of the BCPC was revealed in more late periods of implantation.
      After 6 months, presence of large composite fragments located in intertrabecula
      spaces of greater trochanter was a characteristic feature of the PCPC crushing.
      The developed CPC materials seems to have good perspective for using in bone
      defect plasty in some loaded areas of the skeleton.

PMID- 18049876
TI  - Time-dependent effects of pre-aging polymer films in cell culture medium on cell
      adhesion and spreading.
AB  - We have tested the hypothesis that cell adhesion and spreading on polymer films
      are influenced by the amount of time that the polymer films are pre-aged in cell
      culture medium. Cell adhesion and spreading were assessed after a 6-h culture on
      poly(D,L-lactic acid) (PDLLA) films that had been pre-aged in cell culture medium
      for 30 min, 1, 3 or 7 d. Cell adhesion and spread area were enhanced as the
      duration of pre-aging PDLLA films in cell culture medium was increased. Materials
      characterization showed that the hydrophobicity and surface morphology of the
      PDLLA films changed with increasing length of pre-aging time. These results
      suggest that cell adhesion and spreading are sensitive to the time-dependent
      changes in PDLLA hydrophobicity and surface morphology that occur during exposure
      of the polymer to cell medium for different lengths of time. These results
      demonstrate that cell response to a degradable, biomedical polymer can change as
      a function of the amount of time that the polymer is exposed to physiological
      medium.

PMID- 18049877
TI  - Fabrication of biphasic calcium phosphates/polycaprolactone composites by melt
      infiltration process.
AB  - Synthesis and characterization of material properties of biphasic calcium
      phosphates (BCP)/polycaprolactone (PCL) composites, which were obtained by melt
      infiltration of PCL using porous BCP bodies, were investigated. Using 70 vol.% of
      poly methyl methacrylate (PMMA) powder as a pore-forming agent, porous BCP bodies
      were obtained by pressure less sintering depending on the temperature. The porous
      bodies obtained showed interconnected, spherical pores about 200 microm in
      diameter. Densification of the pore frame improved and grain growth increased
      remarkably as the sintering temperature increased. Molten PCL was infiltrated
      into porous BCP bodies to obtain the BCP/PCL composites. The material properties
      such as the relative density, hardness, bending strength, and elastic modulus of
      BCP/PCL composite, which was sintered at 1200 degrees C, were 95.7%, 11.2 Hv,
      31.6 MPa and 10.2 GPa, respectively.

PMID- 18049878
TI  - Proangiogenic potential of a collagen/bioactive glass substrate.
AB  - PURPOSE: Previous attempts to stimulate angiogenesis have focused on the delivery
      of growth factors and cytokines, genes encoding for specific angiogenic inductive
      proteins or transcription factors, or participating cells. While high
      concentrations of bioactive glasses have exhibited osteogenic potential, recent
      studies have demonstrated that low concentrations of particular bioactive glasses
      are angiogenic. We hypothesized that a well known bioactive glass (Bioglass 45S5)
      possesses proangiogenic potential over a limited range of concentrations.
      MATERIALS AND METHODS: Varying amounts of Bioglass were loaded into absorbable
      collagen sponges. The proangiogenic potential of Bioglass was determined by
      examining the capacity of the soluble products to induce endothelial cell
      proliferation, tubule formation in a co-culture, and upregulate vascular
      endothelial growth factor (VEGF) production. RESULTS: We determined a range of
      Bioglass concentrations which exhibit proangiogenic potential. Furthermore, we
      demonstrated that the proangiogenic capacity of this material is related to the
      soluble dissolution products of Bioglass and the subsequent production of cell
      secreted angiogenic factors by stimulated cells. CONCLUSIONS: These studies
      suggest that this bioactive glass possesses a robust proangiogenic potential, and
      this strategy may provide an alternative to recombinant inductive growth factors.

PMID- 18049879
TI  - Clinical utility of predictors of return-to-work outcome following work-related
      musculoskeletal injury.
AB  - INTRODUCTION: Clinical expertise is one source of evidence that is generally
      under-utilised in the development of an evidence-base in rehabilitation. The
      current study aimed to incorporate this valuable clinical expertise in
      determining the utility of multiple predictors of return-to-work outcome
      following injury. METHODS: Following systematic review of the rehabilitation
      literature and review, a total of 85 predictors were evaluated for clinical
      relevance by an expert panel of rehabilitation practitioners (n = 12). Each
      predictor was rated according the importance of the predictor in rehabilitation,
      its potential for modification and its classification into one of seven broad
      areas. In addition, practitioners were asked to provide a rationale as to why the
      predictor was important to rehabilitation. Analyses were conducted using inter
      rater agreement statistics and text analysis. RESULTS: Predictors that were most
      commonly reviewed in the literature were not considered to be of greatest
      clinical utility, according to the current sample. From the total predictor set,
      only nine predictors were identified as clinically useful (i.e., both highly
      important and highly modifiable). Text analysis of the qualitative data revealed
      that these nine predictors highlighted the significance of time, context and
      engagement in rehabilitation practice. CONCLUSION: In the current study,
      predictors that were considered most clinically relevant were those that
      generally described workplace related processes. The findings confirmed the
      underlying supportive and collaborative processes that integrate predictors and
      account for their influence on outcome. Future rehabilitation efforts and indeed,
      individual outcomes, could benefit by incorporating these key predictors in
      targeted programs.

PMID- 18049880
TI  - Acid synthesis of luminescent amine-functionalized or erbium-doped silica spheres
      for biological applications.
AB  - In this work we discuss and investigate the morphological and optical properties
      of luminescent silica spheres which can have interesting applications in
      bioimaging and biosensing. The spheres are synthesized following an acid route by
      the hydrolysis and condensation of tetraethylortosilicate (TEOS) and can be
      functionalized by incorporation of aminopropyl-triethoxysilane (APTES) during the
      synthesis, inducing a significant luminescence that can be attributed to a
      recombination mechanism from localized organic defects related to -NH(2) groups.
      It is shown that the acid synthesis route produces very regular spherical
      particles, but their diameter vary in the range of 200-4,000 nm. The luminescence
      properties have been investigated and optimized by variation of the annealing
      temperature for the functionalized spheres, obtaining the most efficient PL
      emission after a thermal treatment of 1 h at 600 degrees C in air. Moreover, the
      possibility to introduce rare earths like erbium in the spheres was also studied
      and the corresponding Er(3) luminescence emission at 1.53 microm is reported in
      terms of intensity and lifetime, pointing out that erbium can be easily and
      efficiently incorporated during the acid synthesis giving high PL intensity with
      a good lifetime of 3.9 ms.

PMID- 18049881
TI  - Equilibrium analysis of the DNA binding domain of the ultraspiracle protein
      interaction with the response element from the hsp27 gene promoter--the
      application of molecular beacon technology.
AB  - Ecdysteroids initiate molting and metamorphosis in insects via a receptor which
      belongs to the superfamily of nuclear receptors. The ecdysone receptor consists
      of two proteins: the ecdysone receptor (EcR) and the ultraspiracle (Usp). The EcR
      Usp dimer conducts transcription through a hsp27(pal) response element. Usp acts
      as an anchor orienting the whole complex on the DNA. The molecular beacon
      methodology was applied to detect the sequence-specific DNA of a natural hsp27
      (pal) or mutated protein interaction with the DNA binding domain from the Usp.
      The dissociation constant, K(d), of the UspDBD-hsp27 (pal) complex was determined
      to be 1.42+/-0.48 nM, whereas K(d) for UspDBD(DeltaA)-hsp27(pal) was 6.6+/-0.5
      nM. Mutation of Val-71 for Ala blocks formation of the protein-DNA complex in
      contrast to Glu-19 mutation for Ala for which K(d)=4.31+/-1.01 nM. The results
      obtained with the molecular beacon technology are related to those obtained by
      fluorescence anisotropy titrations.

PMID- 18049882
TI  - Two-photon absorption properties of 9,10-disubstituted 2,6-bis(p
      dihexylaminostyryl)anthracene derivatives. Effect of 9,10-substituents.
AB  - A series of 2,6-bis(p-dihexylaminostyryl)anthracence derivatives having phenyl,
      styryl, and phenylethynyl groups at 9,10-positions (1-4) have been synthesized
      and their two-photon cross-sections were determined. Overall, the wavelengths of
      the longest wavelength absorption band and emission spectra increase with
      increase in the conjugation length and the electron withdrawing ability of the
      9,10-substituents. All compounds show two-photon cross sections in the range of
      740-3940 GM at 780-960 nm, which increase significantly by the donor and acceptor
      groups at 9,10-positions. In addition, Ph and phenylethynyl groups are better
      when compared to the styryl group at the 9,10-positions in terms of the two
      photon action cross section. From a practical perspective, 1a, 2a-c, and 4b
      showed significant two-photon action cross-section and are most useful for
      applications that use two-photon excited fluorescence.

PMID- 18049883
TI  - Study of structural and photoluminescent properties of Ca8Eu2(PO4)6O2.
AB  - In this work it is presented for the first time the nanostructured
      hydroxyapatites doped with 0.5, 1.0 and 2.0 wt% of Eu(3+) prepared at room
      temperature by the mechanical alloying technique. X-ray diffraction powder (XRD),
      infrared (IR) and Raman scattering spectroscopy, scanning electron microscopy
      (SEM), microhardness measurements as well as luminescent data of Eu(3+) were used
      to investigate the structural and optical properties of these nanomaterials. The
      electrical and dielectrical analyses were used with the intention of having a
      better comprehension about the electromagnetic fields in pure and doped
      hydroxyapatites.

PMID- 18049884
TI  - Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic
      cell maturation and polarization via thymic stromal lymphopoietin.
AB  - Human exposure to air pollutants, including ambient particulate matter, has been
      proposed as a mechanism for the rise in allergic disorders. Diesel exhaust
      particles, a major component of ambient particulate matter, induce sensitization
      to neoallergens, but the mechanisms by which sensitization occur remain unclear.
      We show that diesel exhaust particles upregulate thymic stromal lymphopoietin in
      human bronchial epithelial cells in an oxidant-dependent manner. Thymic stromal
      lymphopoietin induced by diesel exhaust particles was associated with maturation
      of myeloid dendritic cells, which was blocked by anti-thymic stromal
      lymphopoietin antibodies or silencing epithelial cell-derived thymic stromal
      lymphopoietin. Dendritic cells exposed to diesel exhaust particle-treated human
      bronchial epithelial cells induced Th2 polarization in a thymic stromal
      lymphopoietin-dependent manner. These findings provide new insight into the
      mechanisms by which diesel exhaust particles modify human lung mucosal immunity.

PMID- 18049885
TI  - A multilevel analysis of state and regional disparities in childhood and
      adolescent obesity in the United States.
AB  - This study examines state- and regional disparities in obesity prevalence among
      46,707 US children and adolescents aged 10-17 years before and after adjusting
      for individual socioeconomic and behavioral characteristics and area deprivation
      measures. The 2003 National Survey of Children's Health was used to calculate
      obesity prevalence in nine geographic regions and in the 50 states and the
      District of Columbia (DC). Logistic regression was used to estimate odds of
      obesity and adjusted prevalence. OLS regression was used to determine the amount
      of variance explained by income inequality, poverty, and violent crime rates. The
      prevalence of childhood obesity varied substantially across geographic areas,
      with the Southcentral regions of the US having the highest prevalence (> or =18%)
      and the Mountain region the lowest prevalence (11.4%). Children in West Virginia,
      Kentucky, Texas, Tennessee, and North Carolina (adjusted prevalence >18.3%) had
      over twice the odds of being obese than their Utah counterparts (adjusted
      prevalence = 10.4%). Geographic disparities in obesity were similar for male and
      female children. Individual characteristics such as race/ethnicity, household
      socioeconomic status, neighborhood social capital, television viewing,
      recreational computer use, and physical activity accounted for 55% of the state
      and 25% of the regional disparities in obesity. Area poverty rates accounted for
      an additional 18% of the state variance in adjusted obesity prevalence. Although
      individual and area level socioeconomic factors are important predictors,
      substantial geographic disparities in childhood and adolescent obesity remain.
      Prevention efforts targeting individual risk factors as well as contextual social
      and environmental factors may reduce geographic disparities in childhood and
      adolescent obesity.

PMID- 18049887
TI  - The sequence and model structure analysis of three Polish peanut stunt virus
      strains.
AB  - Peanut stunt virus (PSV) belongs to the Cucumovirus genus of the family
      Bromoviridae and is widely distributed worldwide, also in Poland. PSV is a common
      pathogen of a wide range of economically important plants. Its coat protein (CP),
      similarly as in other viruses, plays an important role in many processes during
      viral life cycle and has great impact on the infectivity. In this study, we
      present the results of sequence-structure analysis of CP derived from three
      Polish strains of PSV: PSV Ag, G, and P. Sequences were determined using RT-PCR
      amplification followed by sequencing and compared with each other and also with
      CP from other known PSV viruses. We analyzed their phylogenetic relationship,
      based on CP sequence, using bioinformatic tools as well as their spatial model
      using homology-modeling approach with combination of ROSETTA algorithm for de
      novo modeling. We compared our model with those recently obtained for other
      cucumoviruses including PSV-Er. Our results have shown that all Polish strains
      probably belong to the first subgroup of PSV viruses. Homology level between
      strains Ag and G proved very high. Using theoretical modeling approach we
      obtained a model very similar to the one resolved previously with the differences
      caused by slightly different amino acid sequence. We have also undertaken an
      attempt to analyze its distant regions; however, results are not unequivocal.
      Analysis of symptoms and their correlation with specific amino acid position was
      also performed on the basis of results published elsewhere. The definite
      interpretation is impeded by the presence of satellite RNAs in Ag and P strains
      modulating symptoms' severity, though.

PMID- 18049886
TI  - Complete nucleotide sequence and experimental host range of Okra mosaic virus.
AB  - Okra mosaic virus (OkMV) is a tymovirus infecting members of the family
      Malvaceae. Early infections in okra (Abelmoschus esculentus) lead to yield losses
      of 12-19.5%. Besides intensive biological characterizations of OkMV only minor
      molecular data were available. Therefore, we determined the complete nucleotide
      sequence of a Nigerian isolate of OkMV. The complete genomic RNA (gRNA) comprises
      6,223 nt and its genome organization showed three major ORFs coding for a
      putative movement protein (MP) of M r 73.1 kDa, a large replication-associated
      protein (RP) of M r 202.4 kDa and a coat protein (CP) of M r 19.6 kDa. Prediction
      of secondary RNA structures showed three hairpin structures with internal loops
      in the 5'-untranslated region (UTR) and a 3'-terminal tRNA-like structure (TLS)
      which comprises the anticodon for valine, typical for a member of the genus
      Tymovirus. Phylogenetic comparisons based on the RP, MP and CP amino acid
      sequences showed the close relationship of OkMV not only to other completely
      sequenced tymoviruses like Kennedya yellow mosaic virus (KYMV), Turnip yellow
      mosaic virus (TYMV) and Erysimum latent virus (ErLV), but also to Calopogonium
      yellow vein virus (CalYVV), Clitoria yellow vein virus (CYVV) and Desmodium
      yellow mottle virus (DYMoV). This is the first report of a complete OkMV genome
      sequence from one of the various OkMV isolates originating from West Africa
      described so far. Additionally, the experimental host range of OkMV including
      several Nicotiana species was determined.

PMID- 18049888
TI  - Tat protein vaccination of cynomolgus macaques influences SHIV-89.6P cy243
      epitope variability.
AB  - In a previous study we showed that vaccination with the native Tat protein
      controlled virus replication in five out of seven monkeys against challenge with
      the simian human immunodeficiency virus (SHIV)-89.6P cy243 and that this
      protection correlated with T helper (Th)-1 response and cytotoxic T lymphocyte
      (CTL) activity. To address the evolution of the SHIV-89.6P cy243 both in control
      and vaccinated infected monkeys, the sequence of the human immunodeficiency virus
      (HIV)-1 Tat protein and the C2-V3 Env region of the proviral-DNA-derived clones
      were analyzed in both control and vaccinated but unprotected animals. We also
      performed analysis of the T cell epitope using a predictive epitope model taking
      into consideration the phylogeny of the variants. Our results suggest that even
      though the viral evolution observed in both groups of monkeys was directed toward
      variations in the major histocompatibility complex (MHC)-I epitopes, in the
      control animals it was associated with mutational escape of such epitopes. On the
      contrary, it is possible that viral evolution in the vaccinated monkeys was
      linked to mutations that arose to keep high the viral fitness. In the vaccinated
      animals the reduction of epitope variability, obtained prompting the immune
      system by vaccination and inducing a specific immunological response against
      virus, was able to reduce the emergence of escape mutants. Thus the intervention
      of host's selective forces in driving CTL escape mutants and in modulating viral
      fitness appeared to be different in the two groups of monkeys. We concluded that
      in the vaccinated unprotected animals, vaccination with the Tat protein induced a
      broad antiviral response, as demonstrated by the reduced ability to develop
      escape mutants, which is known to help in the control of viral replication.

PMID- 18049889
TI  - The effects of GnRH antagonist on the endometrium of normally menstruating women.
AB  - PURPOSE: To study the effects of GnRH antagonist (ganirelix-Orgalutran) on the
      endometrium of regularly menstruating women. MATERIALS AND METHODS: Prospective,
      self-controlled study. The thirty-five volunteers were studied for two cycles:
      one as a control and the other, GnRH antagonist-treated cycles in which ganirelix
      0.25 mg/d was given daily for 3 days, starting when the largest follicle reached
      15 mm. In both cycles, serum estradiol, LH and endometrial thickness were
      measured when the largest follicle was > or =18 mm. Endometrial biopsy was
      performed on day 6 after ovulation for histological dating and morphometric
      study. RESULTS: No statistical differences between histological dating and the
      endometrial thickness in the control and GnRH antagonist-treated cycles. All
      morphometric parameters were also not different. Serum estradiol and LH levels
      were significantly lower in GnRH antagonist-treated cycles. CONCLUSION: GnRH
      antagonist has no effect on the endometrium of regularly menstruating women as
      assessed by either histological dating or morphometric analysis.

PMID- 18049890
TI  - Single nucleotide polymorphisms of the aromatase gene (CYP19A1), HER2/neu status,
      and prognosis in breast cancer patients.
AB  - PURPOSE: Estrogen exposure is involved in both breast cancer susceptibility and
      the prognosis in patients with breast cancer. Aromatase is involved in the
      production of estrogens, and altered expression of it might be associated with
      the prognosis. The aim of this study was to examine the effect of single
      nucleotide polymorphisms (SNPs) in the aromatase gene, CYP19A1, on the prognosis,
      and in relation to tumor and patient characteristics in a cohort of breast cancer
      patients. PATIENTS AND METHODS: The cohort analyzed in this study consisted of
      1,257 patients with invasive primary breast cancer. Polymorphisms rs10046, rs4646
      and rs700519 were genotyped within this group. RESULTS: The variant genotypes of
      rs10046 and rs4646 were associated with a lower percentage of HER2-positive
      tumors. There was no association of rs700519 and rs4646 with disease-free
      survival (DFS) or overall survival (OS). The variant genotype of rs10046 was
      significantly associated with a better 5-year DFS (hazards ratio 0.51; 95% CI,
      0.32 to 0.81; P=0.004) adjusted for age, nodal status, tumor size grading, and
      hormone receptor status. This effect appeared to be determined in the subgroup of
      premenopausal patients. CONCLUSION: SNPs rs10046 and rs4646 may influence the
      HER2 status of breast cancer tumors, and rs10046 genotypes are associated with an
      altered DFS. Genotypes of aromatase polymorphisms may influence the prognosis for
      breast cancer patients not only by affecting the extent of estrogen exposure but
      also through an alteration in tumor characteristics.

PMID- 18049891
TI  - NBS1 variant I171V and breast cancer risk.
AB  - The NBS1/p95 protein has a pivotal role in the sensing and repair of chromosome
      breaks. A missense mutation in the NBS1 gene, I171V, has recently been associated
      with a ninefold increased risk of breast cancer in Polish patients. Positive
      associations have also been reported for leukaemia and larynx cancer suggesting
      that I171V could be a more general susceptibility factor for malignancies. We
      investigated the prevalence of this mutation in two large hospital-based case
      control series from Germany and from the Republic of Belarus. The I171V
      substitution was detected in 20/1,636 Byelorussian breast cancer patients and in
      18/1,014 Byelorussian controls (OR: 0.68; 95%CI: 0.36-1.30, P=0.3). The I171V
      substitution was furthermore detected in 10/1,048 German breast cancer patients
      and in 7/1,017 German controls (OR: 1.39; 95%CI: 0.53-3.67, P=0.7). There were no
      significant differences between I171V carriers and non-carriers among the cases
      with regard to age at diagnosis, family history or bilateral occurrence of
      disease. A meta-analysis of all hitherto available studies did not reveal a
      difference in the prevalence of I171V between breast cancer cases and controls
      (OR: 1.05; 95%CI: 0.64-1.74, P=0.9). We conclude that the I171V substitution is
      unlikely to constitute a strong risk factor for breast cancer in our study
      populations.

PMID- 18049892
TI  - Commentary to "Interaction between Abeta peptide and alpha synuclein: molecular
      mechanisms in overlapping pathology of Alzheimer's and Parkinson's in dementia
      with Lewy body disease".

PMID- 18049893
TI  - Antioxidant enzyme activities following acute or chronic methylphenidate
      treatment in young rats.
AB  - Methylphenidate (MPH) is psychostimulants used to treat Attention
      Deficit/Hyperactivity Disorder and can lead to a long-lasting neurochemical and
      behavioral adaptations in experimental animals. In the present study, the
      cerebral antioxidant enzymatic system, superoxide dismutase (SOD) and catalase
      (CAT) was evaluated at in different age following MPH (1, 2 or 10 mg/kg MPH,
      i.p.) treatment in young rats. In the acute treatment the SOD activity decreased
      in the cerebral prefrontal cortex with opposite effect in the cerebral cortex;
      and the CAT activity decreased in hippocampus. In the chronic treatment the SOD
      activity increased in the hippocampus and cerebral cortex and decreased in the
      striatum. The observed changes on the enzyme activities in rat brain were
      dependent on the structure brain region and duration of treatment with MPH.
      Probably, the activity of enzymes was not be enough to prevent MPH-induced
      oxidative damage in specific regions from brain, such as observed for us in
      another recent study.

PMID- 18049894
TI  - Screening for postpartum depression in a rural community.
AB  - Postpartum depression is a serious mental health issue affecting as many as 10
      15% of families during the postpartum period. The current study discusses
      implementation of a screening protocol for postpartum depression in a rural
      community health setting with a sample of 498 primarily minority women utilizing
      the Postpartum Depression Screening Scale. Results indicate that 22.5% of the
      sample population demonstrate some symptoms of postpartum depression, with
      Hispanic women demonstrating less symptoms than other minority groups. Results
      also indicate that variables such as race, feeding method and history of
      depression impact scale scores.

PMID- 18049895
TI  - Path models of quality of life among people with schizophrenia living in the
      community in Hong Kong.
AB  - The utilization of quality of life (QOL) in psychiatric community rehabilitation
      could be enhanced by developing an appropriate conceptual model of QOL. The focus
      of this study was to construct and test, using path analytic techniques, a
      pertinent conceptual model of QOL among people with schizophrenia living in the
      community. A total of 201 participants with schizophrenia living in the community
      were assessed with regard to their clinical characteristics and QOL. Findings
      largely supported the proposed model in which community/social functioning was
      the strongest predictor of QOL, followed by symptom levels. Important
      implications for the design and implementation of appropriate services in
      functioning augmentation that resulted in QOL enhancement were highlighted.
      Further recommendations on both clinical and environmental interventions to
      promote QOL were suggested.

PMID- 18049896
TI  - Outcome from a community-based smoking cessation program for persons with serious
      mental illness.
AB  - Six and 12-month outcomes are reported on 79 mentally ill persons attending
      either a 4- or 8-session community-based smoking cessation group. Quit rates at
      post, 3-, 6-, and 12-month follow-ups were 16, 19, 16, and 19%, respectively,
      with no significant effect of program length. These success rates are comparable
      to outcomes reported following group-based treatment with mentally healthy
      smokers. The majority of quitters used nicotine replacement therapy. Psychotropic
      medication dosages did not vary over time in quitters or non-quitters. No
      reductions in smoking were observed among non-quitters. Quitting smoking had no
      untoward effects on symptoms of mental illness or general functioning.

PMID- 18049897
TI  - Anti-Saccharomyces cerevisiae antibodies in primary biliary cirrhosis.
AB  - AIM: The aim of this study was to evaluate, retrospectively, the frequency of
      anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with primary biliary
      cirrhosis (PBC). METHODS: ASCA, IgG, and IgA, were determined by ELISA in sera of
      95 PBC patients; 80 healthy blood donors served as controls. RESULTS: The
      frequency of ASCA (IgG or IgA) was significantly higher in PBC patients than in
      the control group (24.2% vs 3.7%, P = 0.0001). The frequency of ASCA IgG and ASCA
      IgA in PBC patients was also significantly higher than that found in the control
      group (18.9% vs 2.5%, P = 0.0006 and 11.6% vs 1.2%, P = 0.007, respectively). Six
      patients out of 95 (6.3%) had both ASCA IgG and ASCA IgA; in contrast, none of
      the control group had both isotypes (P = 0.02). There was no correlation between
      ASCA levels and mitochondrial autoantibodies (AMA) titres in PBC patients.
      CONCLUSION: We conclude that ASCA are common in patients with PBC.

PMID- 18049898
TI  - The short-term effects of different doses of dexamethasone on the numbers of some
      bacteria in the ileum.
AB  - Glucocorticoids are known to affect intestinal biota both directly or indirectly.
      The aim of the study reported here was to determine the short-term effects of
      different doses of dexamethasone on the numbers of various ileal bacteria
      populations. Rats were randomly put into groups, and each group was administered
      a single-dose injection of dexamethasone at either 0.1, 0.5, 1, 2.5, 5, or 10
      mg/kg body weight. At 48-h post-injection, the numbers of total aerobe, anaerobe,
      lactobacilli and coliform bacteria in the ileum were determined. The numbers of
      total aerobes and lactobacilli were higher in the groups receiving 5 and 10 mg/kg
      dexamethasone than in the control and other dose groups (P < 0.01 and P < 0.001,
      respectively). The number of ileal anaerobic bacteria was higher in group
      receiving 5 mg/kg than in the other groups (P < 0.01). There were more coliform
      bacteria in the group receiving 0.1 mg/kg than in the groups receiving 0.5, 1 and
      10 mg/kg (P < 0.05). In light of these results, the effects of dose-dependent
      increases in the number of different bacterial groups affecting gut functions
      have still to be determined in future studies.

PMID- 18049899
TI  - Tumour necrosis factor alpha in segmental colitis associated with diverticula.
AB  - The pathogenesis of segmental colitis associated with diverticula (SCAD) is
      unclear, but tumour necrosis factor alpha (TNF-alpha) has been shown to play a
      pivotal role in the pathogenesis of inflammatory bowel diseases. The aim of this
      study was to assess TNF-alpha levels in patients with SCAD. In a post hoc
      analysis of a prospective multicenter study, tissue samples from 13 patients
      diagnosed with SCAD were subjected to histological analyses. The severity of the
      inflammation was assessed by means of a histological score and histomorphometry
      (number of inflammatory cells/mm2). Immunohistochemical staining with an antibody
      against TNF-alpha was performed on all biopsies and the degree of staining
      expressed as the percentage of positive stromal cells/1000 counted (TNF-alpha
      score). Matched patients with irritable bowel syndrome (IBS) were used as
      controls. Over-expression of TNF-alpha was found in all SCAD patients (38.6 +/-
      10.4%), and it was associated with a high histological score (2.5 +/- 0.5) and
      neutrophil cell count (16.3 +/- 3/mm2). These values were distinctly higher than
      those found in the IBS controls. Our data suggest that TNF-alpha activity is
      involved in SCAD pathogenesis, similarly to what occurs in Crohn's disease and
      ulcerative colitis.

PMID- 18049900
TI  - Liver histology changes in nonalcoholic steatohepatitis after one year of
      treatment with probucol.
AB  - BACKGROUND: Probucol, a lipid-lowering agent with antioxidant effects, is
      effective in normalizing liver enzymes in patients with nonalcoholic
      steatohepatitis (NASH). We studied changes in the liver histology of patients
      with NASH after use of probucol for one year. METHODS: Ten patients with biopsy
      proven NASH were included. Subjects were given 500 mg probucol daily. Liver
      biopsies were performed before treatment and after one year. RESULTS: Eight
      patients completed treatment. The mean alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) levels decreased from 94 and 55 to 41 and 26,
      respectively (P = 0.004 and 0.001 respectively). The scores for hepatic steatosis
      and necroinflammation decreased from 7.4 to 5.6 (P = 0.03). The fibrosis score
      changed from 1.1 to 1.3 (P = 0.79). No adverse drug effects were observed.
      CONCLUSION: Probucol is effective in normalizing aminotransferase levels in
      patients with NASH. It also significantly reduces the histology grade of
      steatohepatitis after one year of treatment.

PMID- 18049901
TI  - Simvastatin attenuates trinitrobenzene sulfonic acid-induced colitis, but not
      oxazalone-induced colitis.
AB  - PURPOSE: To determine whether simvastatin is able to inhibit inflammation in
      trinitrobenzene sulfonic acid (TNBS)-induced or oxazalone (OXA)-induced colitis.
      RESULTS: In the prophylactic protocol, simvastatin dose-dependently suppressed
      the decrease in body weight and inflammatory grade of TNBS-treated mice. In
      contrast, in the therapeutic protocol, no significant difference in body weight
      reduction was observed between simvastatin-treated and control mice. IFN-gamma
      release from LP cells was significantly suppressed in mice receiving high-dose
      simvastatin in the prophylactic protocol. In contrast to TNBS colitis, even high
      dose prophylactic simvastatin had no suppressive effects on either weight
      reduction or the inflammatory grade in OXA colitis. CONCLUSION: Our results
      indicate that simvastatin negatively regulates inflammation in TNBS-induced
      colitis, but not in OXA-induced colitis. In TNBS-induced colitis, simvastatin
      suppressed the Th1-polarized immune response. Our findings suggest that
      simvastatin has potential effects as a therapeutic agent in human inflammatory
      bowel disease, particularly Crohn's disease.

PMID- 18049902
TI  - Characterization of hemodynamic forces induced by mechanical heart valves:
      Reynolds vs. viscous stresses.
AB  - Bileaflet mechanical heart valves (BMHV) are widely used to replace diseased
      heart valves. Implantation of BMHV, however, has been linked with major
      complications, which are generally considered to be caused by mechanically
      induced damage of blood cells resulting from the non-physiological hemodynamics
      environment induced by BMHV, including regions of recirculating flow and elevated
      Reynolds (turbulence) shear stress levels. In this article, we analyze the
      results of 2D high-resolution velocity measurements and full 3D numerical
      simulation for pulsatile flow through a BMHV mounted in a model axisymmetric
      aorta to investigate the mechanical environment experienced by blood elements
      under physiologic conditions. We show that the so-called Reynolds shear stresses
      neither directly contribute to the mechanical load on blood cells nor is a proper
      measurement of the mechanical load experienced by blood cells. We also show that
      the overall levels of the viscous stresses, which comprise the actual flow
      environment experienced by cells, are apparently too low to induce damage to red
      blood cells, but could potentially damage platelets. The maximum instantaneous
      viscous shear stress observed throughout a cardiac cycle is <15 N/m(2). Our
      analysis is restricted to the flow downstream of the valve leaflets and thus does
      not address other areas within the BMHV where potentially hemodynamically
      hazardous levels of viscous stresses could still occur (such as in the hinge gaps
      and leakage jets).

PMID- 18049903
TI  - Acetylcholine inhibits long-term hypoxia-induced apoptosis by suppressing the
      oxidative stress-mediated MAPKs activation as well as regulation of Bcl-2, c
      IAPs, and caspase-3 in mouse embryonic stem cells.
AB  - This study examined the effect of acetylcholine (ACh) on the hypoxia-induced
      apoptosis of mouse embryonic stem (ES) cells. Hypoxia (60 h) decreased both the
      cell viability and level of [3H] thymidine incorporation, which were prevented by
      a pretreatment with ACh. However, the atropine (ACh receptor [AChR] inhibitor)
      treatment blocked the protective effect of ACh. Hypoxia (90 min) increased the
      intracellular level of reactive oxygen species (ROS). On the other hand, ACh
      inhibited the hypoxia-induced increase in ROS, which was blocked by an atropine
      treatment. Subsequently, the hypoxia-induced ROS increased the level of p38
      mitogen activated protein kinase (MAPK) and Jun-N-terminal kinase (JNK)
      phosphorylation, which were inhibited by the ACh pretreatment. Moreover, hypoxic
      exposure (90 min) increased the level of nuclear factor-kappa B (NF-kappa B)
      phosphorylation, which was blocked by a pretreatment with SB 203580 (p38 MAPK
      inhibitor) or SP 600125 (JNK inhibitor). However, hypoxia (60 h) decreased the
      protein levels of Bcl-2 and c-IAPs (cellular inhibitor of apoptosis proteins) but
      increased the level of caspase-3 activation. All these effects were inhibited by
      a pretreatment with ACh. In conclusion, ACh prevented the hypoxia-induced
      apoptosis of mouse ES cells by inhibiting the ROS-mediated p38 MAPK and JNK
      activation as well as the regulation of Bcl-2, c-IAPs, and caspase-3.

PMID- 18049905
TI  - Prospective investigation into the influence of various stressors on skin
      impedance.
AB  - BACKGROUND: The control mechanisms during general anesthesia include circulation
      parameters and vegetative reactions. A possible way to quantify vegetative
      reactions is to measure the impedance of the skin. An activation of the eccrine
      sweat glands via sympathetic sudomotor fibers induces a secretion of sweat, which
      generates a drop in skin impedance. The aim of the present study was to
      investigate the influence which different stressors and measurement electrodes
      have upon skin impedance. MATERIAL AND METHOD: The changes in skin impedance and
      were measured after application of various stimuli (T1 value at rest, T2 acoustic
      stimulus, T3 visual stimulus, T4 tactile stimulus, T5 pain stimulus, T6 Valsalva
      manoeuvre, T7 forced inspiration/expiration). About 62 awake subjects underwent
      four standardized test sequences, during which several types of electrodes and
      recording sites (palmarly, plantarly) were explored. RESULTS: All physiological
      (T6-T7) and external stimuli (T2-T5) led to significant changes in skin impedance
      (14.9 +/- 18.2 kOmega) and heart rate. These changes happened independently of
      BMI, gender and measurement electrode types. The time it took to react to the
      stimuli was significantly shorter for palmar applications than that obtained from
      plantar sites. The reaction times were as follows: palmarly 1.2 +/- 0.5 seconds
      for solidgel electrodes and 1.15 +/- 0.5 seconds for hydrogel electrodes,
      plantarly 2.3 +/- 1.0 seconds for solidgel electrodes and 2.21 +/- 1.2 seconds
      for hydrogel electrodes. The forced inspiration and expiration manoeuvres
      generated greater variations in skin impedance than did pain stimulus and
      acoustic stimulus. Measurements that were performed with solidgel electrodes
      revealed significantly greater average decreases in skin impedance following
      exposure to a stimulus. CONCLUSION(S): External, but primarily also physiological
      stressors, generate direct and reproducible variations in skin impedance.
      Solidgel ECG electrodes should be used for all measurements.

PMID- 18049904
TI  - Glucocorticoid receptor physiology.
AB  - Glucocorticoid action in cells is mediated by a specific receptor protein, the
      glucocorticoid receptor (GR). GR is a member of a superfamily of ligand-inducible
      transcription factors that control a variety of physiological functions; such as,
      metabolism, development, and reproduction. Unliganded GR is predominantly
      localized within the cytoplasm but rapidly and efficiently translocates to the
      nucleus following hormone binding. This review will focus on the intracellular
      signaling pathway utilized by the GR including the mechanisms that control its
      intracellular trafficking, hormone binding and transcriptional regulation. Many
      receptor-interacting proteins are involved in distinct steps in GR signal
      transduction, each with a unique mechanism to regulate receptor action and
      providing potential drug targets for the manipulation of cellular responses to
      glucocorticoids.

PMID- 18049906
TI  - Concentrations and inventories of polycyclic aromatic hydrocarbons and
      organochlorine pesticides in watershed soils in the Pearl River Delta, China.
AB  - The concentration levels, source, and inventories of polycyclic aromatic
      hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in 55 surface vegetable
      soils in the watershed of the Pearl River Delta (PRD) were analyzed and compared
      with those of the surface sediments in the Pearl River Estuary (PRE) and northern
      South China Sea (SCS). The 16 priority PAHs on US EPA list range from 58 to 3,077
      microg/kg (average: 315 microg/kg). The concentrations of DDTs and HCHs range
      from 3.58 to 831 microg/kg (average: 82.1 microg/kg) and from 0.19 to 42.3
      microg/kg (average: 4.42 microg/kg). The ratios of DDT/ (DDD+DDE) are higher than
      2 in majority of the soil samples, suggesting that DDT contamination still
      exists. The PAH ratios suggest that the source of PAHs is petroleum, and
      combustion of fossil fuel, biomass, and coal. The average concentrations of PAHs
      and the linear regression slope between PAHs and TOC for the soils and the
      sediments are quite similar. It was estimated that the soil mass inventories at 0
      20 cm depth are 1,292 metric tons for PAHs and 356 metric tons for OCPs in the
      studied region. The average PAHs inventory per unit area for the soil samples
      investigated in PRD is about 0.86 time that of surface sediments in the Pearl
      River Estuary, and about 2.43 times that of surface sediments in the northern
      South China Sea. PAHs in the soils in PRD have similar source to those of the
      surface sediments in PRE. All of those may suggest that PAHs in PRE and SCS are
      probably mainly inputted from the soils in PRD via soil erosion and river
      transport.

PMID- 18049907
TI  - The role of atmospheric circulation system playing in coupling relationship
      between spring NPP and precipitation in East Asia area.
AB  - In many East Asia regions, spring (from March to May) precipitation is an
      important restricting factor to vegetation growth, and atmospheric circulation
      system may influence spring precipitation patter. It is helpful to under the
      response of ecosystem to climate change by studying the influence of atmospheric
      circulation system on the coupling relationship between spring net primary
      productivity and precipitation. Driving CASA (Carnegie-Ames-Stanford Approach)
      NPP (Net Primary Productivity) model, we estimated spring NPP for East Asia area
      (70 degrees E-1 70 degrees E, 10 degrees N-70 degrees N) from 1982 to 1999, and
      by the method of singular value decomposition we further analyzed the coupling
      features of spring NPP with precipitation. The result showed that the response
      features of NPP to precipitation were mainly embodied within the leading six NPP
      precipitation paired-modes. The interpretation rates of the leading six paired
      modes to the covariance of NPP-precipitation were 42.91, 23.29, 9.96, 5.60, 5.04
      and 3.95%, respectively, and total to 90.75%. The temporal correlation
      coefficients of the leading six paired-modes were 0.830, 0.889, 0.841, 0.747,
      0.912 and 0.923, respectively, and all the correlations were significant at
      significant level of 0.001. In some high latitude regions, there was no obviously
      corresponding relationship between NPP and precipitation in the leading two
      paired-modes, and the reason of it may be that spring temperature was the main
      restricting factor to NPP. In middle and low latitude regions, the effect of
      precipitation on NPP was relatively more notable. Nine atmospheric circulation
      factors in spring affected the patterns of NPP and precipitation greatly, and the
      regions with interpretation rate over 50% shared 60.41 and 65.58% of the whole
      study area, respectively.

PMID- 18049908
TI  - Molecular assembly of Zn porphyrin complexes using synthetic light-harvesting
      model polypeptides.
AB  - Synthetic single alpha-helix hydrophobic polypeptides, which have similar amino
      acid sequences to the hydrophobic core in the native light-harvesting 1-beta
      polypeptide from Rhodobacter sphaeroides, formed Zn porphyrin complexes on a gold
      electrode, as well as in n-octyl-beta-glucoside micelles: this process is
      dependent on the structure of the pigments and the polypeptides. Interestingly,
      an enhanced photoelectric current was observed when Zn mesoporphyrin monomer
      complexed with the synthetic light-harvesting model polypeptide in an alpha
      helical configuration was assembled with a defined orientation onto the
      electrode. Analog of these light-harvesting model complexes are also useful in
      providing insights into the effect of polypeptide structure on the formation of
      light-harvesting complexes on and off electrodes.

PMID- 18049909
TI  - Shenfu injection suppresses apoptosis by regulation of Bcl-2 and caspase-3 during
      hypoxia/reoxygenation in neonatal rat cardiomyocytes in vitro.
AB  - Shenfu injection (the major components of which are ginsenosides compound,
      extract of Panax ginseng shown to have antioxidant properties) is a well-known
      important Chinese traditional medicine used for the treatment of various diseases
      especial for cardiac diseases. The precise mechanism of the biological actions of
      this plant is not fully understood, in order to elucidate the protection of
      cardiomyocytes. The aim of the present study was to investigate the effect of
      Shenfu injection on hypoxia/reoxygenation (H/R)-induced apoptosis and the
      expression of bcl-2 and caspase-3 in cultured neonatal rat cardiomyocytes in
      vitro. Ventricular myocytes were isolated from neonatal rat hearts and were
      exposed to 4 h of hypoxia followed by 16 h of reoxygenation. The results
      indicated that treatment with different doses of Shenfu injection protected
      cardiacmyocyte cultures from hypoxia/reoxygenation-induced apoptosis. Caspase-3
      activation was decreased in hypoxic/reoxygenationed cardiomyocytes co-treated
      with Shenfu injection when compared to hypoxia/reoxygenation alone treated
      cultures. Expression of the Bcl-2 proteins was increased in Shenfu injection
      treated cardiomyocytes subjected to hypoxia/reoxygenation. In conclusion,
      ginsenosides compound has obviously protective effects on cardiacmyocytes against
      apoptosis induced by hypoxia/reoxygenation injury, whose mechanisms probably
      involve the inhibition of down-regulation of Bcl-2 protein levels and sequential
      activation of caspase-3.

PMID- 18049923
TI  - Potential ecological and human health impacts of antibiotics and antibiotic
      resistant bacteria from wastewater treatment plants.
AB  - The occurrence of antibiotics and other pharmaceuticals in the environment has
      become an increasing public concern as recent environmental monitoring activities
      reveal the presence of a broad range of persistent pharmaceuticals in soil and
      water. Studies show that municipal wastewater treatment plants (WWTPs) are
      important point sources of antibiotics and antibiotic-resistant bacteria in the
      environment. The fate of antibiotics and other pharmaceuticals in WWTPs is
      greatly influenced by the design and operation of treatment systems. Because
      knowledge on the fate of antibiotics and resistant bacteria in WWTPs is important
      in estimating their potential impacts on ecology and human health, investigations
      on occurrence, treatment, and observed effects are reviewed in this article. In
      addition, human health risk assessment protocols for antibiotic and resistant
      bacteria are described. Although data on other pharmaceutical compounds are also
      presented, discussion is focused on antibiotics in the environment because of the
      potential link to increased emergence of resistance among pathogenic bacteria.
      The applications of modern analytical methods that facilitate the identification
      of novel transformation products of pharmaceuticals in environmental matrices are
      also included to illustrate that the disappearance of the parent pharmaceuticals
      in WWTPs does not necessarily equate to their complete removal.

PMID- 18049911
TI  - The extracolonic cancer spectrum in females with the common 'South African' hMLH1
      c.C1528T mutation.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant
      disease, characterized by the occurrence of predominantly colon and endometrial
      cancer and, less frequently, cancer of the small bowel, stomach, hepatobiliary
      tract, ureter, renal pelvis, ovaries and brain. The phenotypic diversity may
      partially be explained by allelic heterogeneity. The aim of this study was to
      investigate the frequency of extracolonic cancers in a cohort of females sharing
      the same c.C1528T disease-predisposing mutation in the hMLH1 gene. Data on cancer
      history were obtained from 87 mutation-positive females and 121 mutation-negative
      sisters, as a control group. Testing for microsatellite instability (MSI) and
      expression of the wild-type hMLH1 allele was performed on extra-colonic tumour
      tissue blocks of mutation-positive individuals. Extracolonic cancer occurred in
      14% (12/87) of mutation-positive females vs. 7% (8/121) of mutation-negative
      females (P = 0.10). Multiple primary cancers occurred at a significantly higher
      incidence in the first group. Breast cancer, which was the most frequent extra
      colonic cancer in mutation positive females (53%), occurred at a young age, and
      occurred bilaterally in two out of seven cases. Involvement of the hMLH1 gene was
      confirmed in five out of seven cases of breast cancer, two cases of endometrial
      cancer, one case of ovarian cancer and one case of renal cell carcinoma, by
      detecting immunohistochemical compromise of the gene product. Although the study
      might not have been adequately statistically powered (to provide a significant P
      value), the noteworthy findings in this study include the confirmation of a range
      of Lynch II type cancers in a cohort we previously thought was wholly predisposed
      to Lynch I features, and a confirmation of breast cancer as part of the spectrum
      of Lynch syndrome cancers affecting women.

PMID- 18049924
TI  - A review of Thimerosal (Merthiolate) and its ethylmercury breakdown product:
      specific historical considerations regarding safety and effectiveness.
AB  - Thimerosal (Merthiolate) is an ethylmercury-containing pharmaceutical compound
      that is 49.55% mercury and that was developed in 1927. Thimerosal has been
      marketed as an antimicrobial agent in a range of products, including topical
      antiseptic solutions and antiseptic ointments for treating cuts, nasal sprays,
      eye solutions, vaginal spermicides, diaper rash treatments, and perhaps most
      importantly as a preservative in vaccines and other injectable biological
      products, including Rho(D)-immune globulin preparations, despite evidence, dating
      to the early 1930s, indicating Thimerosal to be potentially hazardous to humans
      and ineffective as an antimicrobial agent. Despite this, Thimerosal was not
      scrutinized as part of U.S. pharmaceutical products until the 1980s, when the
      U.S. Food and Drug Administration finally recognized its demonstrated
      ineffectiveness and toxicity in topical pharmaceutical products, and began to
      eliminate it from these. Ironically, while Thimerosal was being eliminated from
      topicals, it was becoming more and more ubiquitous in the recommended
      immunization schedule for infants and pregnant women. Furthermore, Thimerosal
      continues to be administered, as part of mandated immunizations and other
      pharmaceutical products, in the United States and globally. The ubiquitous and
      largely unchecked place of Thimerosal in pharmaceuticals, therefore, represents a
      medical crisis.

PMID- 18049925
TI  - Environmental chemicals: from the environment to food, to breast milk, to the
      infant.
AB  - Food is a source of exposure to many environmental chemicals found in human milk
      and other biological specimens. Ingestion of foods containing high amounts of
      animal fat is the main route of human exposure to lipophilic chemicals, such as
      persistent organic pollutants, which tend to bioaccumulate in the lipid
      compartment. Bioaccumulation results in increased exposure of these chemicals for
      humans, but particularly to breastfeeding infants, who are at the top of the food
      chain. The extent to which food contributes to a person's overall exposure
      depends on individual dietary habits and the concentrations of chemical residues
      in the food. These, in turn, are affected by (1) application methods, (2)
      properties and amounts of the chemical, and (3) preparation, handling, and the
      properties of the food. Once the food is ingested by the lactating woman, the
      chemical's pharmacokinetics and the transport mechanisms producing the movement
      of solutes across mammary alveolar cells determine the passage of chemicals from
      the blood to the milk. Thus, several factors affect the presence in human milk of
      environmental chemicals from dietary sources.

PMID- 18049926
TI  - The occurrence and incorporation of copper and zinc in hair and their potential
      role as bioindicators: a review.
AB  - This article reviews evidence that suggests Cu and Zn concentrations are not
      altered significantly by exogenous processes and may be useful in applications of
      hair analysis. The review attempts to identify what Cu and Zn concentrations may
      actually indicate biogenically and investigates the mechanisms by which they are
      incorporated into hair. Associations with specific hair components are proposed
      and avenues for development as a bioindicator are identified. Areas of research
      that offer promise in application or confirming the use of Cu and Zn are also
      indicated. Correlations and relationships with other health disorders are
      reviewed. Endogenous blood concentrations may also explain alterations in hair
      structure relating to breast cancer.

PMID- 18049927
TI  - Noncholinesterase effects induced by organophosphate pesticides and their
      relationship to cognitive processes: implication for the action of acylpeptide
      hydrolase.
AB  - Organophosphate pesticides have been classically described as inhibitors of
      acetylcholinesterase (AChE) activity in insects and invertebrates. However, there
      is now more evidence supporting the hypothesis that these compounds also act
      through noncholinergic pathways, especially those related to cognitive processes.
      The enzyme acylpeptide hydrolase was identified as a new target for
      organophosphate pesticides. This enzyme is more sensitive than AChE to some
      organophosphates (OP), including dichlorvos, which is the parent compound for
      metrifonate, a therapeutic agent used in the treatment of cognitive impairment
      associated to Alzheimer's disease. Therefore, there is some doubt as to whether
      the mechanism of action of this drug is mediated by a potentiation of cholinergic
      transmission. However, the direct action of acylpeptide hydrolase in cognitive
      processes and the physiological and molecular mechanisms underlying subacute
      exposure to OP have yet to be demonstrated. This review deals with evidence
      demonstrating the existence of mechanisms of actions of OP, which are independent
      of cholinergic pathway potentiation and which have an effect on cognitive
      processes. In addition, the possible participation of the enzyme acylpeptide
      hydrolase in these processes is also discussed. Finally, the possibility of using
      this enzyme activity as a new biomarker for exposure to OP is considered.

PMID- 18049928
TI  - A tribute to the legacy of John Bowlby at the centenary of his birth.

PMID- 18049929
TI  - Babies and toddlers in non-parental daycare can avoid stress and anxiety if they
      develop a lasting secondary attachment bond with one carer who is consistently
      accessible to them.
AB  - Babies and toddlers will have their attachment seeking response activated in the
      absence of the primary or a secondary attachment figure when they are in the
      presence of a stranger and in unfamiliar surroundings. Between the ages of about
      6 months and 30 months, babies and toddlers can only terminate their attachment
      seeking response by reaching proximity to an attachment figure, and unless this
      can be achieved their attachment seeking response will remain unterminated. This
      is the experience of many babies and toddlers each day during certain forms of
      non-parental daycare. Day-care without access to a secondary attachment figure is
      more likely to be the case in group settings such as day-nurseries, than when
      care is provided by an individual carer such as a childminder, nanny, or
      grandmother, who is more likely to be a secondary attachment figure. This paper
      discusses the likelihood of babies and toddlers being able to terminate their
      attachment seeking response during different forms of non-parental daycare, and
      discusses some of the psychological defence processes (including dissociation),
      that may be activated when the attachment seeking response remains unterminated
      throughout the day. This paper briefly examines a model of non-parental daycare
      that actively promotes and monitors long-term secondary attachment bonds between
      baby and carer.

PMID- 18049930
TI  - Attachment theory and John Bowlby: some reflections.
AB  - The 100th anniversary of Edward John Mostyn Bowlby's birth (February 26th, 1907)
      was celebrated at the Tavistock Clinic in London by his family and colleagues,
      with presentations of ongoing research as well as reflections on both the person
      and his theory. My own reflections include the influence of ethological thinking
      on the development of attachment theory, Bowlby's focus on observations followed
      by explanation, his appreciation of emotional communication as well as behavior,
      and his recognition of the role of the family as well as the child/caregiver
      dyad. While always remaining open to new avenues of research, John Bowlby was
      firmly insistent on the precise use of attachment terminology, and quite rightly
      too!

PMID- 18049931
TI  - John Bowlby and couple psychotherapy.
AB  - The centenary of John Bowlby's birth provides a context for considering the
      policy, research and practice legacies that he left for practitioners working in
      many different fields supporting couples and families. Part historical, and part
      forwardlooking, this paper considers the links between attachment in the infant
      parent dyad that was at the heart of Bowlby's concern and the nature of the
      affective ties that bind couples together in adult romantic relationships. An
      overview of the influence of his theory on family policy and adult attachment
      research is followed by an appreciation of its significance for the practice of
      couple psychotherapy. The paper concludes with a comment on the implications of
      current neuroscience knowledge for therapeutic technique.

PMID- 18049932
TI  - John bowlby at the Tavistock.
AB  - Bowlby's best know work at the Tavistock Clinic is his foundational research into
      attachment relationships. This paper describes his other significant
      contributions, as a clinician interested in family dynamics and the impact of
      real events in the genesis of childhood anxieties, and as an institution builder
      in his role in establishing a psychoanalytically based training in Child
      Psychotherapy oriented towards public health.

PMID- 18049933
TI  - Accentuating the positive in adult attachments.
AB  - This paper proposes that attachment theory, with its emphasis on stability and
      security, accentuates the positive aspects of affectional relationships and
      suggests a way to look at the process of adult psychotherapy. Attachment-based
      research has shown that positive attachment experiences are related to feelings
      of joy, comfort, and contentment throughout life. In contrast, experiences that
      are hurtful or traumatic, and especially if they are chronic or repeated, can
      have negative effects on thoughts and emotions as well as the body. In applying
      these findings to psychotherapy, the role of the therapist can be seen as
      providing a positive emotional experience within which to examine and gain a new
      perspective on the origins and development of distress. Through therapy, the
      opportunity to experience a relationship of secure attachment enhances
      psychological and physical well-being and the capacity to make and maintain
      lasting affectional bonds with others.

PMID- 18049934
TI  - A sibling adoption study of adult attachment: the influence of shared environment
      on attachment states of mind.
AB  - This study extends existing research investigating sibling concordance on
      attachment by examining concordance for adult attachment in a sample of 126
      genetically unrelated sibling pairs. The Adult Attachment Interview (George,
      Kaplan, & Main, 1985; Main, Goldwyn, & Hesse, 2003) was used to assess states of
      mind with regard to attachment. The average age of the participants was 39 years
      old. The distribution of attachment classifications was independent of adoptive
      status. Attachment concordance rates were unassociated with gender concordance
      and sibling age difference. Concordance for autonomous/non-autonomous
      classifications was significant at 61% as was concordance for primary
      classifications at 53%. The concordance rate for not-unresolved/unresolved was
      non-significant at 67%. Our findings demonstrate similarity of working models of
      attachment between siblings independent of genetic relatedness between siblings
      and generations (i.e., parent and child). These findings extend previous research
      by further implicating shared environment as a major influence on sibling
      similarities on organized patterns of attachment in adulthood. The non
      significant concordance for the unresolved classification suggests that
      unresolved loss or trauma may be less influenced by shared environment and more
      likely to be influenced by post-childhood experiences or genetic factors.

PMID- 18049935
TI  - Maternal secure base support and preschoolers' secure base behavior in natural
      environments.
AB  - Bowlby and Ainsworth's theory of attachment poses that concurrent caregiving
      behavior is a key factor in influencing and maintaining a child's organization of
      secure-base behavior, and ultimately, security throughout childhood. Empirical
      demonstrations of the relation between the constructs after infancy are
      relatively scant and research is needed to examine the relation between the
      variables across a wide range of contexts, over longer observational periods, and
      in developmentally appropriate ways. Two studies of preschoolers and their
      mothers were conducted in naturalistic settings. Fifty child-mother middle-class
      dyads, predominantly Caucasian, participated in Study 1 and 40 in Study 2. The
      mean age for children was 52 months (Study 1) and 36 months (Study 2). In Study
      1, a home and a playground visits were conducted. In Study 2, two home and a
      playground visits were conducted. Observers used the Maternal Behavior for
      Preschoolers Q-Set to provide age-relevant descriptions of maternal behavior, and
      the Attachment Q-Set to provide descriptions of child behavior. Overall, findings
      indicated that maternal secure base support was significantly related to the
      organization of child secure base behavior (r = .31 and .49 for Study 1 and Study
      2, respectively). Results are discussed in terms of the importance of specifying
      caregiving domains and contexts of assessments, and their implications for
      attachment theory.

PMID- 18049936
TI  - A decade of swings and arrows.

PMID- 18049938
TI  - Influence of menopause on mood: a systematic review of cohort studies.
AB  - OBJECTIVE: This systematic evidence review evaluates the independent influence of
      the menopausal transition on mood including depression, anxiety, and other
      psychological symptoms. METHODS: Community-based, prospective cohort studies of
      mid-life women transitioning through menopause that assessed at least one mood
      symptom on two or more occasions were identified by searches of MEDLINE (1966
      2007) and PsycINFO (1974-2007) databases. Articles were selected based on
      predetermined inclusion and exclusion criteria. Each study was quality-rated by
      three authors; poor quality studies were excluded. RESULTS: Nine studies met
      inclusion criteria. They varied broadly in design, outcome measures, statistical
      methodology, and in consideration of and adjustment for important confounders.
      Five found no association between the menopausal transition and depression,
      negative mood, major depressive disorder, other psychological symptoms, and
      general mental health. Three found that women entering or completing the
      menopausal transition were more likely than premenopausal women to be depressed.
      One found that well-being increased from the early to late menopausal transition.
      CONCLUSION: There is no demonstrated pattern of an adverse independent influence
      of the menopausal transition on mood symptoms in mid-life women. However, the
      available studies are too methodologically diverse to be definitive.

PMID- 18049939
TI  - False alarm: postmenopausal hormone therapy and ovarian cancer.
AB  - BACKGROUND: In a follow-up study of 948,576 women, based on respective relative
      risk (RR) estimates of 1.23 and 1.20 for incident and fatal ovarian cancer among
      current users of postmenopausal hormone therapy (HT), the Million Women Study
      investigators have estimated that, since 1991, HT has resulted in 1300 additional
      cases and 1000 deaths. CRITIQUE: The association was almost entirely confined to
      hysterectomized women, some of whom would not have been at risk because their
      ovaries had been removed; the findings in that group were uninterpretable. Among
      non-hysterectomized women, the RR was 1.12 and compatible with chance. The
      response rate to a follow-up questionnaire was only 64%, and HT-exposed women who
      developed ovarian cancer may selectively have responded. The risk of ovarian
      cancer was no longer increased once women stopped using HT - an effect that was
      pathologically and clinically incompatible with causation. Symptoms of as yet
      undiagnosed ovarian cancer may have 'caused' HT use, rather than the reverse. The
      histological classification of the tumors was not centrally adjudicated. A meta
      analysis of nine studies of current HT use, for which the aggregated RR was 1.28,
      was acknowledged by the investigators to be defective. CONCLUSIONS: Only the
      findings among non-hysterectomized women were to some limited extent
      interpretable and, among them, there was virtually no evidence to suggest that
      current HT use increases the risk of ovarian cancer. It follows that the
      estimated numbers of additional cases of incident and fatal ovarian cancer that
      were attributed to HT use were spurious, and arbitrary extrapolation back to
      1991, which was many years before the Million Women Study, had no scientific
      rationale.

PMID- 18049940
TI  - Individual differences in equol production capability modulate blood pressure in
      tibolone-treated postmenopausal women: lack of effect of soy supplementation.
AB  - OBJECTIVES: Equol, a gut bacterial metabolite of the isoflavone daidzein, has
      been associated with beneficial health effects. Recent studies indicate that
      women with intestinal capacity to convert daidzein to equol also have the
      capacity to alter steroid metabolism and bioavailability of estrogens. METHODS:
      We evaluated whether individual equol production capability, while not consuming
      soy supplement, was associated with lower blood pressure in postmenopausal women
      using tibolone. In addition, in a randomized, placebo-controlled, cross-over
      trial we assessed the effect of soy supplementation on blood pressure in both
      equol-producing (n = 20) and non-equol-producing (n = 20) women using tibolone.
      Blood pressure was recorded with a validated oscillometric technique. RESULTS:
      The circulating equol levels rose 20-fold in the equol producers and 1.9-fold in
      the non-equol producers. At baseline, systolic blood pressure (129.9 +/- 2.6 vs.
      138.5 +/- 3.1 mmHg, p = 0.02), diastolic blood pressure (72.2 +/- 1.5 vs. 76.6 +/
      1.3 mmHg, p = 0.01) and mean arterial blood pressure (93.5 +/- 1.7 vs. 99.9 +/-
      1.8 mmHg, p = 0.007) were lower in equol producers compared to non-equol
      producers. Soy supplementation had no effect on blood pressure in either group,
      whereas the baseline differences persisted. CONCLUSIONS: Postmenopausal women
      using tibolone characterized as equol producers had lower blood pressure compared
      to non-equol producers. Soy supplementation for 2 months had no blood pressure
      lowering effect.

PMID- 18049941
TI  - The influence of smoking on uterine bleeding during continuous and interrupted
      oral hormone therapy.
AB  - OBJECTIVE: To study the influence of smoking on uterine bleeding patterns during
      continuous and interrupted oral hormone therapy (HT). METHODS: Using a post-hoc
      strategy, we included five oral HT groups from three studies. The therapies
      consisted of continuous estrogen (estradiol, estradiol valerate or piperazine
      estrone sulfate) in combination with continuous progestogen (cyproterone acetate,
      gestodene or norethisterone acetate) or in combination with interrupted
      progestogen (norethisterone) given on days 4-6, 10-12, 16-18, 22-24 and 28-30. A
      total of 145 healthy postmenopausal women (54 smokers and 91 non-smokers), who
      had been followed for 2 years, were included in the analyses. Uterine bleeding
      data were collected from bleeding calendars. RESULTS: In general, smoking women
      experienced significantly less days with uterine bleeding per cycle than non
      smoking women during continuous and interrupted HT (0.53 +/- 0.1 vs. 1.6 +/- 0.1;
      p < 0.001). Smoking women were also more likely than non-smoking women to be
      amenorrheic during these therapies (48.2% vs. 29.7%; p < 0.05). Finally, more
      smoking than non-smoking women attained amenorrhea during HT (94.4% vs. 76.9%p <
      0.01). CONCLUSIONS: In healthy postmenopausal women, smoking may reduce uterine
      bleeding during interrupted and continuous HT regimens containing a broad
      selection of estrogens and progestogens. Further study with appropriate
      stratification for smoking status is warranted.

PMID- 18049942
TI  - Moderate alcohol consumption contributes to women's well-being through the
      menopausal transition.
AB  - OBJECTIVES: To examine the association of alcohol consumption with well-being in
      mid-aged Australian women, taking into account other lifestyle factors. METHODS:
      A prospective, observational study was carried out among 438 urban Australian
      women aged 45-55 years at baseline. They were assessed annually for 8 years using
      a questionnaire on health and lifestyle, including self-ratings of well-being and
      daily 'hassles'. Statistical analyses were performed using cluster and repeated
      measures analyses. RESULTS: About 80% of the women had consumed alcohol in the
      week preceding the interview. Alcohol intake was weakly associated with well
      being overall (p = 0.094). Women who consumed alcohol at moderate levels had
      higher well-being scores than non-drinkers or heavy drinkers, however, provided
      they were also non-smokers and exercised weekly or more (p for interaction =
      0.023) (21% of all study participants). Everyday symptoms and stresses had a
      negative impact on well-being (all p values < 0.001). CONCLUSIONS: Among women
      undergoing menopausal transition, well-being is positively associated with
      moderate alcohol consumption along with other lifestyle factors in a synergistic
      fashion, rather than any individual factor having a dominant or an independent
      effect.

PMID- 18049943
TI  - Raloxifene, soy phytoestrogens and endothelial function in postmenopausal women.
AB  - OBJECTIVE: To compare the effects of raloxifene and soy phytoestrogens on
      endothelial function in healthy, postmenopausal women. DESIGN: Randomized, double
      blind, placebo-controlled, cross-over trial. Subjects (n = 22; mean age 58.5
      years) underwent endothelial function testing at baseline and following 6 weeks
      of daily raloxifene 60 mg, soy phytoestrogens 55 mg, and placebo in random
      sequence with intervening 6-week wash-out periods. Endothelial function was
      assessed as flow-mediated vasodilatation (FMD) of the brachial artery using high
      resolution ultrasound; digital flux was measured with laser Doppler velocimetry.
      RESULTS: Baseline (pretreatment) FMD was almost within normal range at 9.6% (+/
      6.4). FMD did not change from baseline within any treatment group, and no between
      group differences were detected. FMD values following treatment with raloxifene,
      soy, and placebo were 10.3% (+/-12.3), 8.3% (+/-7.7), and 9.5% (+/-4.4),
      respectively. Area under curve ratios showed no treatment differences for digital
      velocimetry. CONCLUSIONS: In this study, neither raloxifene nor soy enhanced
      endothelial function in postmenopausal women. However, the cohort had relatively
      normal endothelial function at baseline. Further study is required to determine
      if particular subgroups of postmenopausal women derive vascular benefit from the
      use of selective estrogen receptor modulators or soy phytoestrogens.

PMID- 18049944
TI  - Management of cardiovascular risk in the perimenopausal women: a consensus
      statement of European cardiologists and gynecologists.
AB  - Cardiovascular risk is poorly managed in women, especially during the menopausal
      transition when susceptibility to cardiovascular events increases. Clear gender
      differences exist in the epidemiology, symptoms, diagnosis, progression,
      prognosis and management of cardiovascular risk. Key risk factors that need to be
      controlled in the perimenopausal woman are hypertension, dyslipidemia, obesity
      and other components of the metabolic syndrome, with the avoidance and careful
      control of diabetes. Hypertension is a particularly powerful risk factor and
      lowering of blood pressure is pivotal. Hormone replacement therapy is
      acknowledged as the gold standard for the alleviation of the distressing
      vasomotor symptoms of the menopause, but the findings of the Women's Health
      Initiative (WHI) study generated concern for the detrimental effect on
      cardiovascular events. Thus, hormone replacement therapy cannot be recommended
      for the prevention of cardiovascular disease. Whether the findings of WHI in
      older postmenopausal women can be applied to younger perimenopausal women is
      unknown. It is increasingly recognized that hormone therapy is inappropriate for
      older postmenopausal women no longer displaying menopausal symptoms. Both
      gynecologists and cardiovascular physicians have an important role to play in
      identifying perimenopausal women at risk of cardiovascular morbidity and
      mortality, and should work as a team to identify and manage risk factors, such as
      hypertension.

PMID- 18049946
TI  - Childhood anxiety sensitivity index factors predict unique variance in DSM-IV
      anxiety disorder symptoms.
AB  - Anxiety sensitivity (AS) is an established cognitive risk factor for anxiety
      disorders. In children and adolescents, AS is usually measured with the Childhood
      Anxiety Sensitivity Index (CASI). Factor analytic studies suggest that the CASI
      is comprised of 3 lower-order factors pertaining to Physical, Psychological and
      Social Concerns. There has been little research on the validity of these lower
      order factors. We examined the concurrent and incremental validity of the CASI
      and its lower-order factors in a non-clinical sample of 349 children and
      adolescents. CASI scores predicted symptoms of DSM-IV anxiety disorder subtypes
      as measured by the Spence Children's Anxiety Scale (SCAS) after accounting for
      variance due to State-Trait Anxiety Inventory scores. CASI Physical Concerns
      scores incrementally predicted scores on each of the SCAS scales, whereas scores
      on the Social and Psychological Concerns subscales incrementally predicted scores
      on conceptually related symptom scales (e.g. CASI Social Concerns scores
      predicted Social Phobia symptoms). Overall, this study demonstrates that there is
      added value in measuring AS factors in children and adolescents.

PMID- 18049945
TI  - Cognitive factors that maintain social anxiety disorder: a comprehensive model
      and its treatment implications.
AB  - Social anxiety disorder (SAD) is a common, distressing and persistent mental
      illness. Recent studies have identified a number of psychological factors that
      could explain the maintenance of the disorder. These factors are presented here
      as part of a comprehensive psychological maintenance model of SAD. This model
      assumes that social apprehension is associated with unrealistic social standards
      and a deficiency in selecting attainable social goals. When confronted with
      challenging social situations, individuals with SAD shift their attention toward
      their anxiety, view themselves negatively as a social object, overestimate the
      negative consequences of a social encounter, believe that they have little
      control over their emotional response, and view their social skills as inadequate
      to effectively cope with the social situation. In order to avoid social mishaps,
      individuals with SAD revert to maladaptive coping strategies, including avoidance
      and safety behaviors, followed by post-event rumination, which leads to further
      social apprehension in the future. Possible disorder-specific intervention
      strategies are discussed.

PMID- 18049947
TI  - A quantitative estimate of schema abnormality in socially anxious and non-anxious
      individuals.
AB  - Although cognitive theories of anxiety suggest that anxious individuals are
      characterized by abnormal threat-relevant schemas, few empirical studies have
      estimated the nature of these cognitive structures using quantitative methods
      that lend themselves to inferential statistical analysis. In the present study,
      socially anxious (n = 55) and non-anxious (n = 62) participants completed 3 Q
      Sort tasks to assess their knowledge of events that commonly occur in social or
      evaluative scenarios. Participants either sorted events according to how commonly
      they personally believe the events occur (i.e. "self" condition), or to how
      commonly they estimate that most people believe they occur (i.e. "other"
      condition). Participants' individual Q-Sorts were correlated with mean sorts
      obtained from a normative sample to obtain an estimate of schema abnormality,
      with lower correlations representing greater levels of abnormality. Relative to
      non-anxious participants, socially anxious participants' sorts were less strongly
      associated with sorts of the normative sample, particularly in the "self"
      condition, although secondary analyses suggest that some significant results
      might be explained, in part, by depression and experience with the scenarios.
      These results provide empirical support for the theoretical notion that threat
      relevant self-schemas of anxious individuals are characterized by some degree of
      abnormality.

PMID- 18049948
TI  - Differences in inter-rater reliability and accuracy for a treatment adherence
      scale.
AB  - Inter-rater reliability and accuracy are measures of rater performance. Inter
      rater reliability is frequently used as a substitute for accuracy despite
      conceptual differences and literature suggesting important differences between
      them. The aims of this study were to compare inter-rater reliability and accuracy
      among a group of raters, using a treatment adherence scale, and to assess for
      factors affecting the reliability of these ratings. Paired undergraduate raters
      assessed therapist behavior by viewing videotapes of 4 therapists' cognitive
      behavioral therapy sessions. Ratings were compared with expert-generated
      criterion ratings and between raters using intraclass correlation (2,1). Inter
      rater reliability was marginally higher than accuracy (p = 0.09). The specific
      therapist significantly affected inter-rater reliability and accuracy. The
      frequency and intensity of the therapists' ratable behaviors of criterion ratings
      correlated only with rater accuracy. Consensus ratings were more accurate than
      individual ratings, but composite ratings were not more accurate than consensus
      ratings. In conclusion, accuracy cannot be assumed to exceed inter-rater
      reliability or vice versa, and both are influenced by multiple factors. In this
      study, the subject of the ratings (i.e. the therapist and the intensity and
      frequency of rated behaviors) was shown to influence inter-rater reliability and
      accuracy. The additional resources needed for a composite rating, a rating based
      on the average score of paired raters, may be justified by improved accuracy over
      individual ratings. The additional time required to arrive at a consensus rating,
      a rating generated following discussion between 2 raters, may not be warranted.
      Further research is needed to determine whether these findings hold true with
      other raters and treatment adherence scales.

PMID- 18049949
TI  - Hierarchical model of vulnerabilities for emotional disorders.
AB  - Clark and Watson's (1991) tripartite model of anxiety and depression has had a
      dramatic impact on our understanding of the dispositional variables underlying
      emotional disorders. More recently, calls have been made to examine not simply
      the influence of negative affectivity (NA) but also mediating factors that might
      better explain how NA influences anxious and depressive syndromes (e.g. Taylor,
      1998; Watson, 2005). Extending preliminary projects, this study evaluated two
      hierarchical models of NA, mediating factors of anxiety sensitivity and
      intolerance of uncertainty, and specific emotional manifestations. Data provided
      a very good fit to a model elaborated from preliminary studies, lending further
      support to hierarchical models of emotional vulnerabilities. Implications for
      classification and diagnosis are discussed.

PMID- 18049951
TI  - Sprouty gene expression is regulated by nerve and FGF6 during regeneration of
      mouse muscles.
AB  - Sprouty (Spry) proteins were identified as negative regulators of fibroblast
      growth factor (FGF) signaling in vertebrates and invertebrates. Given the
      importance of the FGFs in myogenesis, we performed cardiotoxin injury-induced
      regeneration experiments on soleus muscles of both, adult control and FGF6 ( - / 
      ) mutant mice and analyzed the accumulation of Spry (1, 2 and 4) transcripts
      using semi-quantitative and real-time RT-PCR assays and in situ hybridization. We
      also analyzed the effects of muscle denervation on the accumulation of Spry
      transcripts. The three Spry genes begin to be expressed as early as the first
      stages of muscle regeneration and are characterized by distinct expression
      patterns. Moreover, Spry gene expression was highly and differentially up
      regulated, precociously by the lack of FGF6, and belatedly by muscle denervation
      strongly suggesting that the transient rise of Spry mRNA accumulation was
      associated to muscle differentiation. Rescue experiments supported the idea of a
      specific relationship between FGF6 and Spry 2, both being known for their
      particular involvement in myogenesis.

PMID- 18049950
TI  - Human brain endothelial cells (HUBEC) promote SCID repopulating cell expansion
      through direct contact.
AB  - The objective of this study was to re-evaluate the previously published
      hematopoietic stem cell (HSC) expansion work using human brain endothelial cells
      (HUBEC). The expansion effect of contact and non-contact conditions was reported
      to be equivalent by others. However, we report here different results that the
      expansion can be achieved only with direct contact. We co-cultured human CD34+
      cells with and without HUBEC contact for seven days with cytokines and the
      readouts were CD34+ / CD38 - phenotype and SCID repopulating cell (SRC)
      frequency. Also tested was the inhibitory effect of Wnt receptor inhibitor Dkk-1
      on HUBEC contact ex vivo expansion; whether an increased expression of Wnt3
      occurs on the HUBEC surface; and detection of an increased nuclear localization
      of beta-catenin in CD34+ / CD38- cells in HUBEC contact culture condition. We
      conclude that the successful expansion by HUBEC contact culture is a candidate
      explanation based on the Wnt family protein, possibly Wnt3, expression on HUBEC.

PMID- 18049952
TI  - Disease-related quantitation of TGF-beta3 in human aqueous humor.
AB  - TGF-beta3 has been implicated in the pathology of ocular diseases, but its
      concentration in human aqueous humor has never been assessed. In this study, we
      established an enzyme-linked immunosorbent assay (ELISA) for TGF-beta3 and
      quantitated it in aqueous humor collected from patients with pseudoexfoliation
      syndrome (PE), primary open angle glaucoma, chronic angle closure glaucoma and
      cataract (as the control). To develop the TGF-beta3 ELISA, we screened antibodies
      to identify the best combination, validated the assay for aqueous humor, and
      optimized the procedure for preparing activated TGF-beta3. As a result, our ELISA
      was highly selective and reproducible. Using our ELISA, we discovered a
      significantly elevated concentration of TGF-beta3 in PE eyes. We also developed
      new TGF-beta1 and -beta2 ELISAs, and were able, for the first time, to quantitate
      all the TGF-beta isoforms in the aqueous humor from a single eye, to assess their
      proportional effects on the pathogenesis of ocular diseases.

PMID- 18049953
TI  - De novo design of beta-helical polypeptides.
AB  - Many proteins, including several growth factor receptors such as the IGF-1R and
      EGFR family, contain variants of the beta-helix fold. Inspection of the irregular
      protein beta-helices suggested that different families of regular beta-helical
      polypeptides can be designed using a series of hinged vectors and the constraints
      imposed by the geometry of a peptide backbone. We have conceived beta-helices
      with five and six beta-strands per turn and designed, in detail, a series of
      regular beta-helices with rhomboidal or triangular cross-sections. Each beta
      helix was modeled by threading C(alpha) atoms to follow the vectorial beta-helix
      and then creating the H-bonded polypeptide backbone and appropriate side-chain
      orientations. The conformational stability of these regular beta-helices was
      assessed using molecular dynamics simulations. Several potential repeat amino
      acid sequences were identified for different geometries of beta-helix. Regular
      beta-helices offer new possibilities for the study of protein folding, the
      production of nanofibers, catalysts, inhibitors of growth factor receptors and
      drug carriers.

PMID- 18049954
TI  - Effects of platelet factors on biodegradation and osteogenesis in metaphyseal
      defects filled with nanoparticular hydroxyapatite--an experimental study in
      minipigs.
AB  - There are no studies on the cellular activity in the early phase of
      biodegradation and bone healing of bone substitutes loaded with platelet factors
      (PLF). The purpose of this study was to evaluate the cellular effects of PLF in
      combination with nanoparticulate hydroxyapatite (HA) on the biodegradation and
      bone formation after 20 days. Autogenous PLFs were obtained by centrifugation of
      miniature pig blood samples and subsequent degranulation of platelets by calcium
      and thrombin. A cylindrical bone defect with a diameter of 8.9 mm was created in
      the distal femoral condyle of 20 miniature pigs. Four of the defects were left
      empty, 8 were filled with HA with loading and 8 with HA loaded with PLF. The
      distal femur was harvested after 20 days and TRAP-staining, cathepsin-K and CD44
      staining and scanning electron microscopy were performed for cellular assessment
      of biodegradation was done. Histomorphometry of new bone formation and of
      biodegradation of HA material was performed. PLF loading of HA led to
      statistically significant more TRAP-positive cells with enhanced biodegradation
      of the nanoparticulate HA but no statistically enhanced new bone formation
      compared to unloaded HA. Furthermore, there was a higher number of CD44 and
      cathepsin-K positive cells by PLF-loading. In summary, PLF led to stimulation of
      the cellular process of the biodegradation of HA.

PMID- 18049955
TI  - Impact of obesity on female reproductive health: British Fertility Society,
      Policy and Practice Guidelines.
AB  - Obesity has a significant adverse impact on reproductive outcome. It influences
      not only the chance of conception but also the response to fertility treatment,
      and increases the risk of miscarriage, congenital anomalies and pregnancy
      complications in addition to potential adverse effects on long term health of
      both mother and infant. Women should aim for a normal BMI before starting any
      form of fertility treatment. Treatment should be deferred until the BMI is less
      than 35 kg/m2, although in those with more time (e.g., less than 37 years; normal
      serum FSH concentration) a weight reduction to a BMI of less than 30 kg/m2 is
      preferable. Clinicians should consider deferring treatment to women outside these
      guidelines. Women should be provided with assistance to lose weight, including
      psychological support, dietary advice, exercise classes and where appropriate,
      weight reducing agents or bariatric surgery. Even a moderate weight loss of 5-10%
      of body weight can be sufficient to restore fertility and improve metabolic
      markers.

PMID- 18049956
TI  - Regulation of female fertility by the endocannabinoid system.
AB  - The role of endocannabinoids in mammalian reproduction is an emerging concept.
      Cannabinoids have been always identified as being harmful drugs, because of their
      negative effects on female reproduction. The discovery of endocannabinoids,
      endogenous lipids that bind to cannabinoid receptors, and of their involvement in
      procreation permitted better understanding of the significance of
      cannabinoid/endocannabinoid signalling in fertilization, preimplantation embryo
      development, implantation and postimplantation embryonic growth. These studies
      have also opened new perspectives in clinical applications, pointing to
      endocannabinoid signalling as a new target for correcting infertility, and for
      improving reproductive health in humans. This review will present
      endocannabinoids, their target receptors and metabolic enzymes, and will discuss
      the involvement of these bioactive lipids in female mammalian reproduction.

PMID- 18049957
TI  - Infertility and its management in men with cystic fibrosis: review of literature
      and clinical practices in the UK.
AB  - Cystic fibrosis (CF) is the most common life-shortening autosomal recessive
      disorder of Caucasians. Most of the men with CF (>95%) have congenital bilateral
      absence of vas deferens (CBAVD), which makes them infertile. However, with
      advances in assisted reproductive techniques, it is now potentially possible for
      these patients to father their own biological children. Spermatozoa may be
      retrieved from either the epididymis or the testes and combined in vitro with
      oocytes retrieved from the female partner. Epididymal sperm may be collected
      either by microsurgical or percutaneous epididymal sperm aspiration. It is
      important to remember that when assisted reproductive techniques are used for
      such patients, there is the inevitability of transmitting a mutated cystic
      fibrosis transmembrane (CFTR) gene, which increases the risk of producing an
      affected child and can have serious long-term implications. It is therefore
      mandatory to offer genetic counselling to the men with CF (and CBAVD) and their
      partners before carrying out assisted reproductive techniques. In the literature,
      there are a very few studies on fertility treatment of these men. However, even
      though the reported number of live births in men with CF is small, given the
      current technology, there are definitely more opportunities for these men to
      become parents.

PMID- 18049958
TI  - Anonymity and openness and the recruitment of gamete donors. Part 2: Oocyte
      donors.
AB  - This invited review paper, the last in a series of two, presents an overview of
      the research evidence concerning oocyte donors' views on anonymity and openness.
      In the period from 2000 to the present, nine such studies that appeared in
      referred journals were located. This research shows that many donors have been
      recruited as personal or known donors, and that many of those who were recruited
      as anonymous donors were willing to be identified to offspring in the future.
      Research from studies of potential donors is presented, and this also indicates
      that recruitment of identifiable donors is possible. The implications of this
      research evidence, particularly as it relates to professional and clinic
      attitudes, the motivations of donors, the demographics of those donors who are
      prepared to be identifiable, and to meeting the needs of donors is highlighted
      and used as the basis for presenting a strategic approach to the recruitment of
      gamete donors--both sperm and oocyte.

PMID- 18049961
TI  - Development and evaluation of Mandarin disyllabic materials for speech audiometry
      in China.
AB  - The purpose of this study is to develop and evaluate disyllabic Mandarin speech
      test materials (MSTMs) in order to facilitate wider use of speech audiometry in
      Chinese audiology clinics. Phonologically balanced Mandarin disyllabic materials
      with high familiarity were designed based on the basic rules for developing
      speech materials and the particular characteristics of Mandarin, and recorded
      digitally. In order to establish the validity and reliability of these Mandarin
      disyllabic materials, equivalence of difficulty between the word lists was
      evaluated for a group of 60 subjects (age-range 18-25 years) with normal hearing.
      Subsequently, performance-intensity (PI) functions were measured in a group of 30
      subjects with normal hearing (age-range 18-25 years), and a group of 35 subjects
      with sensineural hearing loss. The nine lists of Mandarin disyllabic materials
      were found to have sufficient reliability and validity to be used in clinical
      situations.

PMID- 18049962
TI  - Prevalence of hearing impairment in an adult population in Southern Taiwan.
AB  - The objective of this study was to estimate the prevalence of hearing impairment
      in a representative adult population in southern Taiwan and compare the results
      to those of similar studies in other countries. A stratified systematic cluster
      sample of 1140 residents, aged > or =20 years, of Tainan City was studied from
      2001 to 2003. The test battery included otoscopy, pure-tone audiometry, and a
      questionnaire covering relevant personal, occupational, and family history. The
      hearing threshold level (HTL) was defined as the better ear pure-tone average
      (BPTA) (i.e. the average of hearing thresholds at frequencies 500, 1000, 2000,
      and 4000 Hz). The prevalence of hearing impairment was 21.4% (95% confidence
      interval: 19.3-23.7%) at BPTA > or =25 dB HTL. Middle ear disease was a
      significant risk factor for hearing impairment in addition to age and gender. The
      overall prevalence of hearing impairment may be higher in Taiwan (17.1%) than in
      western populations (11.5%), but differences in the definition of hearing
      impairment severity and variation in sex distribution among studies may account
      for this higher prevalence.

PMID- 18049963
TI  - Presbycusis among older Chinese people in Taipei, Taiwan: a community-based
      study.
AB  - The purpose of this study was to estimate the prevalence and severity of
      presbycusis in older Chinese people in Taipei, Taiwan. Pure-tone audiometry and a
      questionnaire were administered to a randomly-recruited cohort of people > 65
      years old (n=1221) from a community in Taipei. The study cohort showed pure-tone
      thresholds worsening, especially at frequencies >2 kHz, with increasing age. The
      mean pure-tone average at speech frequencies (0.5, 1, and 2 kHz) of the better
      ear of subjects stratified by five-year age groups ranged from 34.9 dB hearing
      level (HL) to 46.4 dB HL. The pure-tone average at speech frequency in women was
      slightly higher than that in men in all age groups. The prevalence of presbycusis
      (M3 > or = 55 dBHL) was 1.6% (65-69 years), 3.2% (70-74 years), 7.5% (75-79
      years), and 14.9% (> or =80 years). Persistent tinnitus was present in 13.9% of
      subjects, and 18.8% of subjects had a history of vertigo. Of subjects with a
      clinically evident hearing impairment (M3 > or = 55 dB HL), 18.4% used hearing
      aids. These data provide estimates of the prevalence and severity of presbycusis
      in community-dwelling older persons in Taiwan.

PMID- 18049964
TI  - Toward a standard description of hearing loss.
AB  - Hearing losses are frequently described by categories that characterize the
      configuration, severity, and site of lesion from a pure-tone audiogram. Although
      many category descriptors are in common use, there are no standard definitions of
      those terms, nor have the category definitions been validated against current
      clinical practice. The development and validation of AMCLASStrade mark is
      described. To validate the classification method, five expert judges selected
      configuration, severity, and site of lesion categories for 231 audiograms that
      varied widely in audiometric configuration. Interjudge comparisons indicated that
      expert judges frequently disagree on how they describe an audiogram. Category
      definitions were adjusted to maximize agreement between AMCLASStrade mark and the
      consensus of the judges. The final set of category definitions produced
      categories that agreed with the consensus more often than the average agreement
      between pairs of judges.

PMID- 18049965
TI  - Development of a hearing aid self-efficacy questionnaire.
AB  - Discontinued hearing-aid use is caused by a number of factors, most of which may
      lead to low hearing-aid self-efficacy (i.e. low confidence in one's ability to B
      a successful hearing-aid user). This paper describes the development of the
      Measure of Audiologic Rehabilitation Self-Efficacy for Hearing Aids (MARS-HA),
      which was constructed in accordance with published recommendations for self
      efficacy questionnaire development. The psychometric properties of the MARS-HA
      were evaluated with new and experienced hearing-aid users. The results revealed
      strong internal consistency and good test-retest reliability in both groups, with
      the following subscales identified both for the new users and the experienced
      users: (1) basic handling, (2) advanced handling, (3) adjustment to hearing aids,
      and (4) aided listening skills. Validity was established through the examination
      of expected differences based on group comparisons, training effects, and the
      impact of particular hearing aid features. The MARS-HA is a reliable and valid
      measure of hearing-aid self-efficacy and can be used to assist clinicians in
      identifying areas of low confidence that require additional audiologic training.

PMID- 18049966
TI  - Genetic and environmental influences on hearing at different frequencies
      separately for the better and worse hearing ear in older women.
AB  - The purpose of the present study was to examine the relative contribution of
      genetic and environmental effects on the air-conducted hearing threshold levels
      at low (0.125-0.5 kHz), mid (1-2 kHz), and high (4-8 kHz) frequencies separately
      for the better and worse hearing ear in older women. We also examined the
      distribution of audiogram configurations. Data was analysed using quantitative
      genetic modelling. As part of the Finnish twin study on aging (FITSA), hearing
      was measured in 103 monozygotic and 114 dizygotic female twin pairs aged 63-76
      years. Approximately every third subject had a flat type, and two-thirds a
      descending type of audiogram configuration. No significant difference was
      observed in the distribution of audiogram configurations between zygosity groups.
      In the better ear, additive genetic effects accounted for 64%-74% of the total
      variance at different frequencies. For the worse ear, environmental effects were
      larger. Although overall heritability is rather constant across the frequency
      spectrum, it is noteworthy that at low and high frequencies frequency-specific
      genetic and environmental effects together accounted for the majority of the
      total variance.

PMID- 18049967
TI  - The SCAN-C in testing for auditory processing disorder in a sample of British
      children.
AB  - The SCAN-C is a test for auditory processing disorders in children developed in
      the USA. There are concerns that the SCAN-C may over-diagnose auditory processing
      disorders in UK children. There are also questions concerning the impact of
      language level and interpretation of SCAN-C results. SCAN-C results from 99
      Oxfordshire school children aged 6 to 10 were compared to US-based normative
      data. Across all age bands, the UK sample scored significantly worse on two
      subtests: the filtered words (FW) and auditory figure-ground (AFG) sections as
      well as on the composite score. Differences in performance were largely due to
      accent effects. Applying US norms to UK children's performance results in a high
      rate of over-identification of listening difficulties. However, we show that US
      norms can be used provided SCAN-C scores for children in the UK are adjusted by
      adding a constant. Using factor analysis, SCAN-C subtests mapped onto two
      factors; FW and AFG onto a 'monaural low-redundancy degradation' factor, and CW
      and CS onto a 'binaural separation/competition' factor. Implications for use of
      the SCAN-C with UK children are discussed.

PMID- 18049968
TI  - Communication: access to inclusion.

PMID- 18049969
TI  - The impact of partner training on the communicative involvement of students with
      multiple and severe disability in special schools.
AB  - BACKGROUND: The outcomes of a pilot program of staff development in communication
      support in the context of observed changes in student behaviour states and
      interactive abilities are reported. Participant reports about the impact of the
      program on their professional practices are included. METHOD: Six teachers and
      six teacher aides in special (segregated) schools were provided with a short,
      intensive training program designed to improve their communicative interactions
      with students with multiple and severe disability (MSD) in their classes.
      Behaviour state assessment was used for pre- and post-testing of six students.
      Teachers and aides completed self-report scales related to their communication
      skills, knowledge and concerns prior to and at the conclusion of the training
      program. RESULTS: While staff reported improved skills and knowledge, this was
      not reflected in improvements in the communicative interactions of the students
      as observed in their classrooms. CONCLUSIONS: The training provided may not have
      been sufficient to change well-established teaching and interaction processes.
      Further research using in-school collaborative mentors is planned.

PMID- 18049970
TI  - Presumed competence reflected in the educational programs of students with IDD
      before and after the Beyond Access professional development intervention.
AB  - BACKGROUND: Judgements about students' competence influence the goals of their
      individualised education programs (IEPs), the location of service delivery, and
      their placement in general education (GE) as opposed to special education (SE)
      classes. The purpose of this study was to describe how presumed competence to
      learn the GE curriculum was reflected in the IEPs of students with intellectual
      and developmental disabilities (IDD), and in the reported percentage of time that
      these students spent in GE classes prior to and following the Beyond Access
      professional development intervention. METHOD: Five educational teams of students
      with IDD participated in a professional development intervention that emphasised
      students' presumed competence to learn grade-level GE curriculum. Students' pre-
      and post-intervention IEPs were qualitatively analysed and team member reports of
      percentage time spent in GE classes were averaged. RESULTS: Five categories of
      presumed competence were identified. Following intervention, emphasis on learning
      the GE curriculum, a shift in location of service delivery from outside to within
      the GE classroom, and increased time spent in GE classes were reported.
      CONCLUSIONS: The Beyond Access intervention shows promise for enhancing views of
      the competence of students with IDD to learn the GE curriculum and for increasing
      their inclusion in GE classrooms.

PMID- 18049971
TI  - "Please listen, it's my turn": instructional approaches, curricula and contexts
      for supporting communication and increasing access to inclusion.
AB  - BACKGROUND: Four elementary (primary) school students with severe speech and
      physical impairments (SSPI) who used augmentative and alternative communication
      (AAC) aids were selected to take part in an intensive, 4-week summer intervention
      program. The program was designed to explore effective approaches, content and
      contexts for supporting communication (including oral language, literacy, and
      technology skills) among young people who require AAC. METHOD: Features of the
      intervention included (i) using an integrated approach to provide language and
      literacy opportunities intended to elicit the students' active involvement in
      meaningful, productive and expressive tasks in everyday contexts; (ii) constant
      modelling of AAC usage; (iii) requiring family involvement as a criterion for
      participation in the program; and (iv) follow-up visits to schools during which
      effective instructional strategies were shared with staff. RESULTS: Formative and
      summative assessment measures revealed that all four participants made progress
      during intervention. However two of the students maintained these gains into the
      follow-up period, whereas the other two did not. Each pair seemed to share
      certain characteristics, which are illustrated in this paper by two case study
      synopses. One relates the story of a child whose successes continued into the
      follow-up period, and the other chronicles the experiences of the child whose
      successes quickly waned. CONCLUSIONS: This study provides a range of
      instructional approaches, curricula and contexts to promote communication for
      children with complex communication needs. These instructional supports are more
      likely to improve access to inclusion in schools that seek to work in partnership
      with parents, plan educational transitions, and implement adequate training and
      awareness-raising among their staff.

PMID- 18049972
TI  - Developing social interaction and understanding in individuals with autism
      spectrum disorder: a groupwork intervention.
AB  - BACKGROUND: Difficulties with social interaction and understanding lie at the
      heart of the communication disorder that characterises the autism spectrum. This
      study sought to improve social communication for individuals with autism spectrum
      disorder (ASD) by means of a groupwork intervention focusing on social and
      emotional perspective-taking, conversation skills, and friendship skills. It also
      aimed to address some of the limitations of previous interventions, including a
      lack of generalisation to other settings, so as to maximise inclusion in the
      community. METHOD: A group of 46 high functioning children and adolescents with
      ASD (38 boys, 8 girls, age range 6-16 years) were allocated to one of 6
      intervention groups. Each group met over a period of 12-16 weeks for a minimum of
      one 1(1/2)-hour weekly session aimed at promoting key areas of social interaction
      and understanding, supported by home-based practice. RESULTS: Significant gains
      were achieved in comparison with a normative population, and individual parent
      ratings showed marked and sustained changes in the key areas targeted in the
      group sessions. CONCLUSION: Social communication in children and adolescents with
      ASD can be enhanced through the use of a groupwork intervention addressing social
      interaction and understanding.

PMID- 18049973
TI  - Vocabulary selection for Australian children who use augmentative and alternative
      communication.
AB  - BACKGROUND: Augmentative and alternative communication (AAC)1 systems are
      commonly used to support children with complex communication needs in Australian
      preschools. However, such systems will only be effective if they contain words
      and messages that adequately meet these children's communication needs. The aim
      of this study was to identify the words most frequently and commonly used by
      typically developing Australian preschool-aged children, in order to inform the
      selection of vocabulary for their classmates who use AAC. METHOD: Communication
      samples were collected from 6 typically developing children during regular
      preschool activities. The samples were analysed to determine the number of
      different words used by the children, the frequency with which each word was
      used, and the commonality of use across children. RESULTS: The children used a
      small core vocabulary comprising frequently and commonly used words, together
      with large and highly individualised fringe vocabularies. CONCLUSIONS: The
      results are consistent with the findings of previous studies, and highlight the
      importance of providing both core and fringe vocabulary to preschool-aged
      children who use AAC.

PMID- 18049974
TI  - Perceptions of communication before and after a speech pathology intervention for
      an adult with intellectual disability.
AB  - BACKGROUND: The aim of this study was to explore, from the perspective of key
      communication partners, the meaning of a communication intervention and
      associated changes for an adult with severe intellectual disability (ID). METHOD:
      The parents and key support workers of Mark, a 22-year-old man with ID and
      complex communication needs, were interviewed. The interviews were conducted
      prior to and following a speech pathology intervention and were guided by a
      communication inventory based on the concept of social networks. Interview
      transcripts were analysed qualitatively, with a focus on the subjective meaning
      of communication changes. These changes were explored according to both the
      specific information sought through the inventory and additional information
      provided. RESULTS: The findings were organised into three key themes relating to
      Mark, his familiar communication partners (i.e., parents and disability support
      workers), and the community. Information obtained from the interviews indicated
      that Mark's reported communication level remained stable across the intervention.
      However, an in-depth analysis of the interview transcripts revealed some gains in
      his communication skills. From the perspective of Mark's familiar communication
      partners, key sub-themes emerged which were related to changes in ascription of
      responsibility for developing skills and strategies to enhance Mark's
      communication. Furthermore, greater participation by Mark in his home community
      was evident. CONCLUSIONS: The findings are discussed in terms of the assessment
      of an individual's communication through interactions with communication
      partners, and how changes associated with an intervention can be best understood
      from analysis of rich data.

PMID- 18049975
TI  - An exploration of loneliness: communication and the social networks of older
      people with cerebral palsy.
AB  - BACKGROUND: There is a large body of research focusing on the experiences of
      loneliness of older adults, yet little is known about the loneliness experiences
      of older adults with lifelong disability. In this paper, the authors present some
      findings from a larger qualitative study on the loneliness experiences of older
      people with cerebral palsy. METHOD: Seven older adults with cerebral palsy
      participated in in-depth interviews. Analysis of the interviews identified
      overarching themes and recurrent topics in the data. These topics were coded and
      then grouped under the overarching themes. RESULTS: Six themes were identified.
      All participants agreed that the themes of communication and social networks are
      most important when considering loneliness. In this paper, the participants'
      discussion of these two themes and their related topics are presented.
      CONCLUSIONS: The results demonstrate the need to provide support and training in
      communication to older people with cerebral palsy who experience communication
      difficulty, as well as to their communication partners. They also indicate the
      need for policy development to assist older adults with cerebral palsy to develop
      and maintain their social networks and form relationships that are rewarding and
      enriching.

PMID- 18049977
TI  - The 2007 IAAF Consensus Conference on Nutrition for Athletics.

PMID- 18049979
TI  - Nutrition for the sprinter.
AB  - The primary roles for nutrition in sprints are for recovery from training and
      competition and influencing training adaptations. Sprint success is determined
      largely by the power-to-mass ratio, so sprinters aim to increase muscle mass and
      power. However, extra mass that does not increase power may be detrimental.
      Energy and protein intake are important for increasing muscle mass. If energy
      balance is maintained, increased mass and strength are possible on a wide range
      of protein intakes, so energy intake is crucial. Most sprinters likely consume
      ample protein. The quantity of energy and protein intake necessary for optimal
      training adaptations depends on the individual athlete and training demands;
      specific recommendations for all sprinters are, at best, useless, and are
      potentially harmful. However, if carbohydrate and fat intake are sufficient to
      maintain energy levels, then increased protein intake is unlikely to be
      detrimental. The type and timing of protein intake and nutrients ingested
      concurrently must be considered when designing optimal nutritional strategies for
      increasing muscle mass and power. On race day, athletes should avoid foods that
      result in gastrointestinal discomfort, dehydration or sluggishness. Several
      supplements potentially influence sprint training or performance. Beta-alanine
      and bicarbonate may be useful as buffering agents in longer sprints. Creatine may
      be efficacious for increasing muscle mass and strength and perhaps increasing
      intensity of repeat sprint performance during training.

PMID- 18049980
TI  - Nutritional strategies to optimize training and racing in middle-distance
      athletes.
AB  - Middle-distance athletes implement a dynamic continuum in training volume,
      duration, and intensity that utilizes all energy-producing pathways and muscle
      fibre types. At the centre of this periodized training regimen should be a
      periodized nutritional approach that takes into account acute and seasonal
      nutritional needs induced by specific training and competition loads. The
      majority of a middle-distance athlete's training and racing is dependant upon
      carbohydrate-derived energy provision. Thus, to support this training and racing
      intensity, a high carbohydrate intake should be targeted. The required energy
      expenditure throughout each training phase varies significantly, and thus the
      total energy intake should also vary accordingly to better maintain an ideal body
      composition. Optimizing acute recovery is highly dependant upon the immediate
      consumption of carbohydrate to maximize glycogen resynthesis rates. To optimize
      longer-term recovery, protein in conjunction with carbohydrate should be
      consumed. Supplementation of beta-alanine or sodium bicarbonate has been shown to
      augment intra- and extracellular buffering capacities, which may lead to a small
      performance increase. Future studies should aim to alter specific exercise
      (resistance vs. endurance) and/or nutrition stimuli and measure downstream
      effects at multiple levels that include gene and molecular signalling pathways,
      leading to muscle protein synthesis, that result in optimized phenotypic
      adaptation and performance.

PMID- 18049981
TI  - Nutrition for distance events.
AB  - The goal of training is to prepare the distance athlete to perform at his or her
      best during major competitions. Whatever the event, nutrition plays a major role
      in the achievement of various factors that will see a runner or walker take the
      starting line in the best possible form. Everyday eating patterns must supply
      fuel and nutrients needed to optimize their performance during training sessions
      and to recover quickly afterwards. Carbohydrate and fluid intake before, during,
      and after a workout may help to reduce fatigue and enhance performance. Recovery
      eating should also consider issues for adaptation and the immune system that may
      involve intakes of protein and some micronutrients. Race preparation strategies
      should include preparation of adequate fuel stores, including carbohydrate
      loading for prolonged events such as the marathon or 50-km walk. Fluid and
      carbohydrate intake during races lasting an hour or more should also be
      considered. Sports foods and supplements of value to distance athletes include
      sports drinks and liquid meal supplements to allow nutrition goals to be achieved
      when normal foods are not practical. While caffeine is an ergogenic aid of
      possible value to distance athletes, most other supplements are of minimal
      benefit.

PMID- 18049982
TI  - Nutrition for throwers, jumpers, and combined events athletes.
AB  - Throwers, jumpers, and combined events athletes require speed, strength, power,
      and a wide variety of technical skills to be successful in their events. Only a
      handful of studies have assessed the nutritional needs of such athletes. Because
      of this, recommendations for nutritional requirements to support and enhance
      training and competition performances for these athletes are made using research
      findings from sports and exercise protocols similar to their training and
      competitive events. The goals of the preparation cycle of nutrition periodization
      for these athletes include attaining desirable body weight, a high ratio of lean
      body mass to body height, and improving muscular power. Nutritional
      recommendations for training and competition periods include: (1) meeting energy
      needs; (2) timing consumption of adequate fluid and electrolyte intakes before,
      during, and after exercise to promote adequate hydration; (3) timing consumption
      of carbohydrate intake to provide adequate fuel for energy demands and to spare
      protein for muscle repair, growth, and maintenance; (4) timing consumption of
      adequate protein intake to meet protein synthesis and turnover needs; and (5)
      consuming effective nutritional and dietary supplements. Translating these
      nutrient and dietary recommendations into guidelines these athletes can apply
      during training and competition is important for enhancing performance.

PMID- 18049983
TI  - Physique and performance for track and field events.
AB  - Evidence of the importance of physique in the athletics disciplines is supported
      by the persistence of certain characteristics over long periods, despite marked
      secular changes in the source population. These characteristics may also result
      in physiological benefits such as effective thermoregulation or a greater power
      to-weight ratio. Coaches and athletes are often convinced of weight or fat loss
      benefits based on personal or anecdotal experience, intuition, and "trained eye"
      observation of successful competitors. This may entice athletes into adopting
      unbalanced, erratic or highly restrictive eating patterns that increase the risk
      for nutrient deficiencies, and disordered eating. Despite heavy training loads
      and often extreme diets, some athletes fall short of their physique goals as
      ultimately phenotype is under genetic control. Professionals assisting athletes
      with physique management need to be highly skilled in anthropometry and require a
      thorough understanding of sports-specific nutrition requirements. Careful
      assessment of the risks and benefits of various approaches to weight and fat loss
      is required before they are recommended to athletes.

PMID- 18049984
TI  - The female athlete triad: components, nutrition issues, and health consequences.
AB  - This paper, which was part of the International Association of Athletics
      Federations (IAAF) 2007 Nutritional Consensus Conference, briefly reviews the
      components of the female athlete triad (Triad): energy availability, menstrual
      status, and bone health. Each component of the Triad spans a continuum from
      health to disease, and female athletes can have symptoms related to each
      component of the Triad to different degrees. Low energy availability is the
      primary factor that impairs menstrual dysfunction and bone health in the Triad.
      We discuss nutritional issues associated with the Triad, focusing on intakes of
      macronutrients needed for good health, and stress fractures, the most common
      injury associated with the Triad. Finally, we briefly discuss screening and
      treatment for the Triad and the occurrence of the Triad in men.

PMID- 18049985
TI  - Nutrition for the young athlete.
AB  - Athletics is a popular sport among young people. To maintain health and optimize
      growth and athletic performance, young athletes need to consume an appropriate
      diet. Unfortunately, the dietary intake of many young athletes follows population
      trends rather than public health or sports nutrition recommendations. To optimize
      performance in some disciplines, young athletes may strive to achieve a lower
      body weight or body fat content and this may increase their risk for delayed
      growth and maturation, amenorrhoea, reduced bone density, and eating disorders.
      Although many of the sports nutrition principles identified for adults are
      similar to those for young athletes, there are some important differences. These
      include a higher metabolic cost of locomotion and preferential fat oxidation in
      young athletes during exercise. Young athletes, particularity children, are at a
      thermoregulatory disadvantage due to a higher surface area to weight ratio, a
      slower acclimatization, and lower sweating rate. An appropriate dietary intake
      rather than use of supplements (except when clinically indicated) is recommended
      to ensure young athletes participate fully and safely in athletics.

PMID- 18049986
TI  - Fluid needs for training and competition in athletics.
AB  - The diverse nature of the athletic events, together with the varied training
      programmes and individuality of athletes taking part, inevitably means that fluid
      needs are highly variable--between athletes, perhaps between training and
      competition, and with differing environmental conditions and degree of training
      and heat acclimatization. There are limited data from athletics on all aspects of
      fluid balance, but wherever possible we have focused on this information to draw
      conclusions. When appropriate, euhydration will best be ensured by consuming 6-8
      ml . kg body mass(-1) of a sodium-containing fluid, or sodium-free fluid together
      with food, about 2 h before exercise. The individual sweat responses are so
      variable that athletes should assess their own individual sweat losses to
      determine if these are likely to be a cause for concern. The volume of drink that
      is consumed should never be so much that an athlete gains mass over an event,
      unless perhaps there is evidence that they began in a hypohydrated state. This
      may be a particular concern in the field events and multi-event disciplines when
      competition can be spread over a number of hours and when there are significant
      rest periods between activities.

PMID- 18049987
TI  - Fatigue and illness in athletes.
AB  - Adequate nutrition before, during, and after training and competition is a key
      element to maintaining health. During both sprint and endurance exercise, the
      availability of glycogen is fundamental to performance and any deficit will lead
      to early fatigue. In addition, strategies to offset the negative effects of the
      products of metabolism are presented. Although nutritional strategies can
      attenuate the immunosuppressive effects of exercise, there remains a period of
      susceptibility to infection after a hard exercise session and when this is
      repeated without sufficient recovery an athlete can enter a period of
      "overtraining" during which performance deteriorates. The aetiology and
      identification of this state is not clear and some current ideas are discussed.
      Finally, gastrointestinal problems during running can negate any training
      benefits and we propose some suggestions to reduce this problem.

PMID- 18049988
TI  - The use of dietary supplements by athletes.
AB  - Many athletes use dietary supplements as part of their regular training or
      competition routine, including about 85% of elite track and field athletes.
      Supplements commonly used include vitamins, minerals, protein, creatine, and
      various "ergogenic" compounds. These supplements are often used without a full
      understanding or evaluation of the potential benefits and risks associated with
      their use, and without consultation with a sports nutrition professional. A few
      supplements may be helpful to athletes in specific circumstances, especially
      where food intake or food choice is restricted. Vitamin and mineral supplements
      should be used only when a food-based solution is not available. Sports drinks,
      energy bars, and protein-carbohydrate shakes may all be useful and convenient at
      specific times. There are well-documented roles for creatine, caffeine, and
      alkalinizing agents in enhancing performance in high-intensity exercise, although
      much of the evidence does not relate to specific athletic events. There are
      potential costs associated with all dietary supplements, including the risk of a
      positive doping result as a consequence of the presence of prohibited substances
      that are not declared on the label.

PMID- 18049989
TI  - Innovations in athletic preparation: role of substrate availability to modify
      training adaptation and performance.
AB  - World records for athletic events continue to improve and in the search for
      superior methods to gain a competitive edge, coaches and athletes are constantly
      searching for the latest "magic bullet". Although it is assumed that optimal
      adaptation to the demands of repeated training sessions requires a diet that can
      sustain muscle energy reserves, this premise does not consider the unsolved
      longstanding question of whether it is a lack or a surplus of a substrate that
      triggers the training adaptation. As such, recent scientific enquiry has re
      focused attention on the role of substrate availability before, during, and after
      training to amplify the training adaptation. There has also been a resurgence of
      interest in the potential for protein ingestion to improve performance and/or
      promote training-induced adaptations in skeletal muscle. Altitude training (real
      or simulated) is now an accepted part of competition preparation for many
      athletic events, and such interventions attract their own nutritional issues.
      These and other diet-training interactions with the potential to alter training
      adaptation and performance are discussed.

PMID- 18049990
TI  - Nutrition for travel.
AB  - The training and competitive programmes of elite athletes incorporate travel
      schedules, often long journeys, across multiple time zones. In such cases, travel
      causes both transient fatigue and a malaise known as "jet-lag" that persists for
      some days. Jet-lag is due to the disturbance of the body's circadian rhythms:
      diurnal and performance rhythms are displaced, depending on the direction of
      travel and the number of time zones crossed in flight. Attention to diet and
      hydration is relevant during the flight and following disembarkation until
      adjustment to the new meridian is complete. The consequences of jet-lag on
      rhythms in digestion may be compounded if food preparation and hygiene are
      inadequate in training camps or competitive venues overseas. The irony of travel
      is that it often places athletes at a greater risk of failing to meet their
      specific nutrition goals or succumbing to illness, at a time when the demands or
      outcomes of performance are of greatest importance. In addition, gastrointestinal
      infections related to travelling are frequent among athletes. Fastidious planning
      and organization among the support staff is recommended before the journey to
      prevent any such problems arising. Equally, athletes often need special education
      initiatives to assist them to cope with the challenges of a new and unusual food
      supply, or altered access to food.

PMID- 18049991
TI  - Air pollution and hospital admissions for pneumonia in a tropical city:
      Kaohsiung, Taiwan.
AB  - This study was undertaken to determine whether there was an association between
      air pollutant levels and hospital admissions for pneumonia in Kaohsiung, Taiwan.
      Hospital admissions for pneumonia and ambient air pollution data for Kaohsiung
      were obtained for the period of 1996-2004. The relative risk of hospital
      admission was estimated using a case-crossover approach, controlling for weather
      variables, day of the week, seasonality, and long-term time trends. In the single
      pollutant models, on warm days (= 25 degrees C) statistically significant
      positive associations were found for all pollutants. On cool days (< 25 degrees
      C), all pollutants were also significantly associated with number of pneumonia
      admissions. For the two-pollutant model, O3 and CO were significant in
      combination with each of the other four pollutants on warm days. On cool days,
      PM10 and NO2 remained statistically significant in all the two-pollutant models.
      This study provides evidence that higher levels of ambient air pollutants
      increase the risk of hospital admissions for pneumonia. The effects of air
      pollutants on hospital admissions for pneumonia were temperature dependent.

PMID- 18049992
TI  - Gemfibrozil ingestions reported to Texas poison control centers, 2000-2005.
AB  - Review of the literature failed to identify any information on potentially
      adverse ingestions of the cholesterol-lowering drug gemfibrozil (GEM) reported to
      poison control centers. Data from Texas poison control centers were used to
      describe the pattern of isolated GEM ingestions reported during 2000-2005. A
      total of 118 cases were identified. The mean maximum dose ingested was 2407 mg
      (range 300-18,000 mg) or 3.3 tablets/capsules (range 1-30 tablets/capsules). The
      patient was male in 55% of the cases. The most common circumstances of the
      exposure were unintentional therapeutic error (49%), general unintentional (34%),
      and suspected attempted suicide (11%). The management site was on site (84%),
      already at/en route to a health care facility (10%), referred to a health care
      facility (5%), and other (2%). The ingestion considered potentially toxic in 3%
      of the cases and no deaths were reported. A specific adverse clinical effect was
      listed for 9% of the cases, being gastrointestinal (5%), neurological (3%), or
      cardiovascular (1%). A specific treatment was listed for 54% of the cases, most
      frequently decontamination by dilution (39%) or food (15%). Potentially adverse
      isolated GEM ingestions reported to poison control centers generally do not
      involve serious medical outcomes and are successfully managed at home with a
      favorable outcome.

PMID- 18049993
TI  - Approaches to acrylamide physiologically based toxicokinetic modeling for
      exploring child-adult dosimetry differences.
AB  - Dietary exposure to acrylamide is common as a result of its formation during the
      cooking of carbohydrate foods. This leads to widespread human exposure in adults
      and children alike. Acrylamide is neurotoxic and is metabolized by cytochrome P
      450 (CYP) 2E1 to a mutagenic epoxide, glycidamide. This article describes a
      modeling framework for assessing acrylamide and glycidamide dosimetry in rats and
      human adults and children. The challenges in building a physiologically based
      toxicokinetic (PBTK) model that is compatible with existing rat and human data
      are described, with an emphasis on calibration against the hemoglobin adduct
      database. This exploratory PBTK model was adapted to children by incorporating
      life-stage-specific parameters consistent with children's changing physiology and
      metabolic capacity for processes involved in acrylamide disposition in terms of
      CYP2E1, glutathione conjugation, and epoxide hydrolase. Monte Carlo analysis was
      used to simulate the distribution of internal doses to gain an initial
      understanding of the range of child/adult differences possible. This analysis
      suggests modest dosimetry differences between children and adults, with area
      under-the-curve (AUC) doses for the 99th percentile child up to fivefold greater
      than the median adult for both acrylamide and glycidamide. Early life
      immaturities tended to exert a greater effect on acrylamide than glycidamide
      dosimetry because immaturities in CYP2E1 and glutathione counteract one another
      for glycidamide AUC, but both lead to greater acrylamide dose. The analysis
      points toward glutathione conjugation parameters as being particularly
      influential and uncertain in early life, making this a key area for future
      research.

PMID- 18049994
TI  - A test of association between spatially defined exposure patterns and health
      outcome risk contours.
AB  - Advances in the availability of geographically referenced health and
      environmental quality data of high spatial resolution have created new
      opportunities in environmental epidemiology. Novel statistical methods for
      linking health, exposure, and hazards are required to underpin the development of
      public health tracking. A test for the association between spatial contours of
      health risk and exposure is outlined. This test is examined using, as an example,
      the spatial contours of congenital malformation risk obtained from a routine
      dataset in the vicinity of a landfill site and an exposure model based on
      exponential reduction with distance from the site. Spatial contours of risk of
      congenital malformation were simulated using the exposure model stated and a
      given population pattern. These were compared with the corresponding expected
      risk derived from routine birth data to yield relative risk contours. For each
      simulation three test statistics were devised: the slope of the regression line
      of standardized relative risk on exposure level, the proportion of standardized
      relative risks above zero, and the mean standardized relative risk of individuals
      not subject to exposure. The distributions of these test statistics (under the
      null no exposure from site and alternative hypotheses) were determined from a
      simulation exercise. A comparison of receiver operator characteristic (ROC)
      curves between those relating to the proposed test and those relating to a widely
      used method proposed by Stone (1988) demonstrated our test to be more efficient.
      Formal statistical testing of the concordance between spatial contours of risk
      and environmental exposure enables optimal use of spatial data.

PMID- 18049995
TI  - Hospitalization patterns associated with Appalachian coal mining.
AB  - The goal of this study was to test whether the volume of coal mining was related
      to population hospitalization risk for diseases postulated to be sensitive or
      insensitive to coal mining by-products. The study was a retrospective analysis of
      2001 adult hospitalization data (n = 93,952) for West Virginia, Kentucky, and
      Pennsylvania, merged with county-level coal production figures. Hospitalization
      data were obtained from the Health Care Utilization Project National Inpatient
      Sample. Diagnoses postulated to be sensitive to coal mining by-product exposure
      were contrasted with diagnoses postulated to be insensitive to exposure. Data
      were analyzed using hierarchical nonlinear models, controlling for patient age,
      gender, insurance, comorbidities, hospital teaching status, county poverty, and
      county social capital. Controlling for covariates, the volume of coal mining was
      significantly related to hospitalization risk for two conditions postulated to be
      sensitive to exposure: hypertension and chronic obstructive pulmonary disease
      (COPD). The odds for a COPD hospitalization increased 1% for each 1462 tons of
      coal, and the odds for a hypertension hospitalization increased 1% for each 1873
      tons of coal. Other conditions were not related to mining volume. Exposure to
      particulates or other pollutants generated by coal mining activities may be
      linked to increased risk of COPD and hypertension hospitalizations. Limitations
      in the data likely result in an underestimate of associations.

PMID- 18049996
TI  - Single-walled carbon nanotubes: geno- and cytotoxic effects in lung fibroblast
      V79 cells.
AB  - With the development of nanotechnology, there is a tremendous growth of the
      application of nanomaterials, which increases the risk of human exposure to these
      nanomaterials through inhalation, ingestion, and dermal penetration. Among
      different types of nanoparticles, single-walled carbon nanotubes (SWCNT) with
      extremely small size (1 nm in diameter) exhibit extraordinary properties and
      offer possibilities to create materials with astounding features. Since the
      release of nanoparticles in an enclosed environment is of great concern, a study
      of possible genotoxic effects is important. Our previous data showed that
      pharyngeal aspiration of SWCNT elicited pulmonary effects in C57BL/6 mice that
      was promoted by a robust, acute inflammatory reaction with early onset resulting
      in progressive interstitial fibrogenic response and the formation of granulomas.
      In the present study, the genotoxic potential of SWCNT was evaluated in vitro.
      The genotoxic effects of nanoparticles were examined using three different test
      systems: the comet assay and micronucleus (MN) test in a lung fibroblast (V79)
      cell line, and the Salmonella gene mutation assay in strains YG1024/YG1029.
      Cytotoxicity tests showed loss of viability in a concentration- and time
      dependent manner after exposure of cells to SWCNT. Results from the comet assay
      demonstrated the induction of DNA damage after only 3 h of incubation with 96
      microg/cm2 of SWCNT. The MN test indicated some but not significant micronucleus
      induction by SWCNT in the V79 cell line at the highest concentrations tested.
      With two different strains of Salmonella typhimurium, no mutations were found
      following SWCNT exposure.

PMID- 18049997
TI  - Genotoxicity of organic extracts of house dust from Shanxi, China.
AB  - Indoor combustion of solid fuel such as coal may generate respirable particles
      containing polycyclic aromatic hydrocarbons (PAH) that may adhere to settled
      dust. Dust might therefore present a major source of PAH exposure in humans. This
      study evaluated the in vitro and in vivo genotoxicity of PAH mixtures extracted
      from house dust samples. Four dust samples (E1-4) were collected from houses in
      Shanxi, China, where coal is heavily used for heating and cooking. For
      comparison, a coal sample was also collected from one of the houses and included
      in the analyses. The samples were extracted with methylene chloride:acetone (95:5
      v/v), dried, and redissolved in appropriate solvents for assessment in
      genotoxicity assays. Samples were evaluated for their ability to induce point
      mutations in bacteria and DNA adducts in vivo. DNA adduct levels were analyzed by
      nuclease P1-enhanced 32P-postlabeling. PAH were quantified using gas
      chromatography/mass spectrometry. Based on chemical analysis, sample E1 had the
      highest concentration by sampling area of benzo[a]pyrene (BaP) (181 microg/m2)
      and total PAH (10100 microg/m2). However, based on the microbial genotoxicity
      assay, sample E3, with the highest carcinogenic PAH/total PAH ratio (26%),
      produced the greatest number of revertants. In mice, administration of the
      extract of coal induced more adducts (9.81 adducts per 10(9) nucleotides) than
      dust extracts. The results of this study confirm the presence of genotoxic
      chemicals in residential dust. Inhalation of respirable particles containing
      similar mixtures of PAH represents a cancer risk for humans.

PMID- 18049998
TI  - Evaluating nephrotoxicity of high-molecular-weight organic compounds in drinking
      water from lignite aquifers.
AB  - High-molecular-weight organic compounds such as humic acids and/or fulvic acids
      that are naturally mobilized from lignite beds into untreated drinking-water
      supplies were suggested as one possible cause of Balkan endemic nephropathy (BEN)
      and cancer of the renal pelvis. A lab investigation was undertaken in order to
      assess the nephrotoxic potential of such organic compounds using an in vitro
      tissue culture model. Because of the infeasibility of exposing kidney tissue to
      low concentrations of organics for years in the lab, tangential flow
      ultrafiltration was employed to hyperconcentrate samples suitable for discerning
      effects in the short time frames necessitated by tissue culture systems. Effects
      on HK-2 kidney cells were measured using two different cell proliferation assays
      (MTT and alamarBlue). Results demonstrated that exposure of kidney tissue to high
      molecular-weight organics produced excess cell death or proliferation depending
      on concentration and duration of exposure.

PMID- 18050000
TI  - Prediction of hemispheric asymmetry as measured by handedness from digit length
      and 2D:4D digit ratio.
AB  - Hemispheric asymmetry is widely theorised as having a basis in prenatal androgen
      levels. However, these theories ignore a second round of asymmetrical changes in
      the brain, which occur at the same time as post-puberty surges in androgens.
      Hemispheric asymmetry in adults might therefore be explained in terms of the
      joint effects of prenatal and post-pubertal androgen levels. Evidence is emerging
      that the ratio between the length of the second and fourth digits (2D:4D) is
      related to prenatal androgen exposure, and that digit length is related to post
      puberty levels of androgen exposure. In this study, hemispheric asymmetry is
      measured as handedness, prenatal androgen levels as 2D:4D, and post-puberty
      androgen levels as digit length. Right-handedness is associated with consistent
      prenatal and post puberty androgen release whereas left-handedness is associated
      with mixed levels of androgen release. Age, race, and sex effects were explored
      but were not significant.

PMID- 18049999
TI  - Evaluation of cytotoxicity attributed to thimerosal on murine and human kidney
      cells.
AB  - Renal inner medullary collecting duct cells (mIMCD3) and human embryonic kidney
      cells (HEK293) were used for cytoscreening of thimerosal and mercury chloride
      (HgCl2). Thimerosal and HgCl2 acted in a concentration-dependent manner. In
      mIMCD3 cells the 24-h LC50 values for thimerosal, thiosalicylic acid, 2,2
      dithiosalicylic acid, and 2-sulfobenzoic acid were 2.9, 2200, >1000, and >10,000
      microM, respectively. The 24-h LC50 value for HgCl2 in mIMCD3 cells was 40
      microM. In HEK293 cells, the 24-h LC50 value for thimerosal was 9.5 microM. These
      data demonstrate that the higher cytotoxicity produced by thimerosal on renal
      cells with respect to similar compounds without Hg may be related to this metal
      content. The present study also establishes mIMCD3 cells as a valuable model for
      evaluation of cytotoxicity of nephrotoxic compounds.

PMID- 18050001
TI  - Review and theory of handedness, birth order, and homosexuality in men.
AB  - Research has repeatedly shown that older brothers increase the odds of
      homosexuality in later-born males. This phenomenon has been called the fraternal
      birth order effect. The most highly developed explanation of this phenomenon is
      the maternal immune hypothesis, which proposes that the fraternal birth order
      effect reflects the progressive immunisation of some mothers to male-specific
      antigens by each succeeding male foetus and the concomitantly increasing effects
      of anti-male antibodies on the sexual differentiation of the brain in each
      succeeding male foetus. Recent studies indicate that older brothers increase the
      odds of homosexuality in right-handed males but not in non-right-handed males.
      The present article explores how the maternal immune hypothesis might be extended
      or modified to account for the apparent interaction of older brothers and
      handedness. Two possibilities are considered: (1) non-right-handed foetuses are
      insensitive to the presence of maternal anti-male antibodies, and (2) mothers of
      non-right-handed foetuses do not produce anti-male antibodies.

PMID- 18050002
TI  - A new means of measuring index/ring finger (2D:4D) ratio and its association with
      gender and hand preference.
AB  - Relative finger length can predict a person's gender or their hand preference. We
      measured finger length using a new "tubes" test, which required participants to
      slide a clear plastic tube over their fingers and read the length from an
      attached mm scale. Data collected from 600 students demonstrated that the right
      fingers are longer than the left for dextrals, but not for non-dextrals.
      Examination of the relative length of the index and ring fingers revealed a clear
      gender effect. There was also an effect of hand preference on index/ring finger
      ratio whereby non-dextrals showed a more masculine pattern compared to dextrals.
      For non-dextrals, prenatal exposure to high testosterone levels may have caused
      both a shift away from dextrality and a more masculine pattern of finger ratio.
      In the second experiment, finger length was measured by the tubes test and by
      photocopying the hands in 124 undergraduates. The tubes test yielded a longer
      estimate of ring finger length compared to the photocopy method. Despite this,
      there was a strong correlation between the tests and both showed an association
      with gender. Finally, test-retest scores for 45 participants showed a high level
      of reliability for absolute and relative finger measures. We conclude that the
      tubes technique provides an effective and easy-to-use means of measuring finger
      length, which can be administered in a classroom setting.

PMID- 18050003
TI  - Chimeric faces, visual field bias, and reaction time bias: have we been missing a
      trick?
AB  - The chimeric faces test is a frequently used behavioural test of lateralisation
      for cognitive processing. Performance on this task is typically quantified in
      terms of bias towards selecting faces where positive facial emotion is expressed
      in the viewer's left visual field, indicating right hemisphere dominance for the
      task. This paper examines an alternative measure that may be extracted from
      responses to the chimeric faces test: reaction time bias. There was a strong
      positive correlation between the two asymmetry measures, which remained even
      after controlling for sex and handedness. The possible uses of reaction time bias
      in the measurement of cerebral lateralisation are discussed.

PMID- 18050005
TI  - Post-operative use of remoulding orthoses following cranial vault remodelling: a
      case series.
AB  - The use of external orthoses following surgical cranial vault remodelling in
      infants with craniosynostosis was first described in the 1980s. While a few
      preliminary reports have been published on its use, there are no reports
      outlining specific orthotic considerations. The purpose of this paper is to
      present the orthotic community with an introduction to the various
      craniosynostoses, the resultant cranial morphologies, and specific orthotic
      considerations associated with these morphologies, including trigocephaly,
      frontal plagiocephly, brachycephaly, scapholocephaly, and occipital
      plagiocephaly. For each presentation, guidelines are presented as to where the
      cranial remoulding orthosis should maintain contact, thereby discouraging cranial
      growth, and where the voids should be established and maintained to allow for
      corrective cranial growth. Principles are supported by photographs of
      representative cases.

PMID- 18050006
TI  - Balance control enhancement using sub-sensory stimulation and visual-auditory
      biofeedback strategies for amputee subjects.
AB  - Sub-sensory electrical or mechanical stimulation can enhance the sensitivity of
      the human somatosensory system to improve the balance control capabilities of
      elderly. In addition, clinical studies suggest that visual-auditory biofeedback
      can improve sensory compensation for the elderly. This study hypothesizes that
      the static balance and gait performance of single leg quiet standing and
      treadmill walking could be improved for providing proprioceptive neuromuscular
      facilitation using sub-sensory stimulation and visual-auditory biofeedback in
      amputee subjects. To test this, a computerized foot pressure biofeedback sensory
      compensation system using sub-threshold low-level electrical stimulation combined
      with visual-auditory biofeedback was developed. Seven unilateral trans-tibial
      amputees who wore prostheses over 2 years were recruited. The subjects performed
      multiple single leg quiet standing trials with sub-sensory electrical stimulation
      applied at the quadriceps muscle during half of the trials. Static balance
      performance was characterized by using a Zebris motion analysis system to measure
      the sway distance and duration of the centre of mass on the second sacral (S2) of
      the subjects. In addition, multiple treadmill ambulatory trials with or without
      visual-auditory biofeedback was performed. Dynamic gait performance was
      characterized with a Zebris instrumented insole to measure the temporal responses
      of foot pressure sensors. Experimental results showed an improvement in three
      balance performance indices (Holding Time Index, HTI, Maximum Sway Distance
      Index, MSDI, and Average Sway Distance Index, ASDI) during single leg quiet
      standing by applying sub-sensory stimulation. The improvement ratio of these
      balance performance indices across subjects for single leg quiet standing tests
      resulted in 132.34% in HTI, 44.61% in MSDI, and 61.45% in ASDI. With visual
      auditory biofeedback as a cue for heel contact and toe push-off condition during
      treadmill ambulation, the improvement of four dynamic gait performance measures
      (Double Support Period, DSP, Constant Time Cadence, CTC, Single Support Period,
      SSP, and Stance/Swing Ratio, SSR) in amputees was verified. This resulted in
      7.89% in DSP (affected side), 5.09% in CTC, 16.67% in SSP (sound side), 45.30% in
      SSR (sound side), and 40.30% in SSR (affected side) respectively. These findings
      suggest that sub-threshold electrical stimulation and visual-auditory biofeedback
      rehabilitation strategies may be effective in compensating sensory loss and
      improving static balance and dynamic ambulation performance for amputees.

PMID- 18050007
TI  - Results of an Internet survey of myoelectric prosthetic hand users.
AB  - The results of a survey of 54 persons with upper limb amputations who anonymously
      completed a questionnaire on an Internet homepage are presented. The survey ran
      for four years and the participants were divided into groups of females, males,
      and children. It was found that the most individuals employ their myoelectric
      hand prosthesis for 8 hours or more. However, the survey also revealed a high
      level of dissatisfaction with the weight and the grasping speed of the devices.
      Activities for which prostheses should be useful were stated to include
      handicrafts, personal hygiene, using cutlery, operation of electronic and
      domestic devices, and dressing/undressing. Moreover, additional functions, e.g.,
      a force feedback system, independent movements of the thumb, the index finger,
      and the wrist, and a better glove material are priorities that were identified by
      the users as being important improvements the users would like to see in
      myoelectric prostheses.

PMID- 18050008
TI  - Development of a hinge compatible with the kinematics of the knee joint.
AB  - This study aims to present a new concept of a knee hinge based on a crossed four
      bar linkage mechanism which has been designed to optimally follow a motion curve
      representing the knee kinematics in the position at which the knee hinge should
      be placed. The methodology used to determine the optimal knee hinge is based on
      the optimization of certain variables of the crossed four-bar mechanism using
      genetic algorithms in order to follow a certain motion curve, which was
      determined using a biomechanical model of the knee motion. Two current,
      commercially available knee hinges have been used to theoretically determine
      their motion by means of the path performed by their instantaneous helical axis.
      Comparison between these two different knee hinges, Optimal Knee Hinge and the
      theoretical motion performed by a human knee reveals that a common monocentric
      hinge has a maximum misalignment of up to 27.2 mm; a polycentric hinge has a
      maximum misalignment of 23.9 mm. In contrast, the maximum misalignment produced
      by the Optimal Knee Hinge is 1.99 mm. The orthotic joint presented significantly
      improves the kinematical compatibility and the adjustment between orthotic and
      human joint motion, and should provide several advantages in terms of comfort and
      safety. Furthermore, the determination of the instantaneous helical axis for a
      particular user, by means of human movement measurement techniques, will enable
      the optimal crossed four-bar mechanisms to be determined in a customized and
      personalized manner. As a consequence, this new concept of orthotic knee joint
      design may improve the adaptability of lower limb orthoses for the user, and may
      lead to significant advantages in the field of orthotics for the lower limb.

PMID- 18050009
TI  - Effect of a shock-absorbing pylon on transmission of heel strike forces during
      the gait of people with unilateral trans-tibial amputations: a pilot study.
AB  - The primary objective was to test the hypothesis that walking with a shock
      absorbing pylon (SAP) decreases the peak magnitude and frequency content of the
      heel-strike-initiated shock wave transmitted to the stump. The secondary
      hypotheses were that walking with a SAP decreases the heel-strike transient force
      between the ground and the foot and increases function as measured by walking
      velocity and subjective assessments. Seven people with unilateral trans-tibial
      amputations walked at self-selected speeds without and with a SAP. As the primary
      outcome measure, accelerometers were used mounted proximally and distally along
      the prosthetic pylon to measure the transmitted shock wave. Secondary measures
      included ground reaction forces from a force plate, a ten-minute walking test to
      determine walking speed and a questionnaire to evaluate gait function and
      subjective preference. The SAP provided no significant shock absorption as
      indicated by either the mean peak proximal accelerations of 3.19 g and 2.82 g (p
      = 0.28) without and with the SAP respectively or the mean difference between the
      peak proximal and distal accelerometers, 0.16 g and 0.19 g (p = 0.58). No
      significant change in the frequency content was found. Variances were high. There
      were no significant differences noted in the secondary measures. Although this
      study failed to identify any statistically significant effects due to the SAP,
      the magnitude and variance of the data will permit an accurate estimation of the
      appropriate sample size for future studies required to determine the efficacy of
      SAPs.

PMID- 18050011
TI  - Comment on: animal welfare in experiments.

PMID- 18050010
TI  - Rasch analysis of the Locomotor Capabilities Index-5 in people with lower limb
      amputation.
AB  - The aim of this study was to perform a Rasch analysis on the 5-level ordinal
      scale version of the Locomotor Capabilities Index (LCI-5), in order to
      investigate rating scale quality and conduct reliability and validity
      assessments. A questionnaire was mailed to 144 subjects who had undergone lower
      limb amputation (LLA) in the previous five years and completed a rehabilitation
      and prosthetic training programme. A total of 123 persons (85%) responded to the
      questionnaire, a self-report assessment of prosthetic capability and performance
      which included the LCI-5, the Mobility Section of the Prosthesis Evaluation
      Questionnaire (PEQ-MS) and other variables associated to prosthetic wear and use.
      Following Rasch analysis and expert review, the LCI-5 response categories level 1
      ('yes, if someone helps me') and 2 ('yes, if someone is near me') were combined
      into a single category and 4 items were deleted (due to misfitting). The
      remaining 10 items fitted the Rasch model (LCI10-4) and demonstrated good
      reliability (person separation reliability = 0.94, item separation reliability =
      0.98) and internal construct validity. Moreover, the good correlation with the
      PEQ-MS (r(s) = 0.77) and with prosthetic wear and use (r(s) range 0.34 - 0.51)
      supported the convergent validity of the scale. In conclusion, Rasch analysis
      provided the rationale for improving the measurement qualities of the LCI-5,
      refining its rating scale (through category diagnostics), identifying those items
      most useful for measuring the intended construct (as per the indexes of
      unidimensionality and internal construct validity) and showing that one can place
      high confidence in the consistency of both the person-ability and item-difficulty
      estimates obtained (reliability).

PMID- 18050015
TI  - Renal transplant and secondary hyperparathyroidism.
AB  - OBJECTIVE: To investigate the impact of mineral metabolism, renal function,
      months on dialysis and months since transplant for predicting intact parathyroid
      hormone (iPTH) levels in a cohort of patients who had undergone their first renal
      graft with estimated glomerular filtration rates (eGFRs) of 30-60 and >60
      ml/min/1.73 m2. MATERIAL AND METHODS: One hundred and twenty-eight patients (mean
      age 56.0 +/- 14.6 years) with an eGFR of >30 ml/min/1.73 m2 were included. The
      median time since transplant was 88.6 months (range 2.8-403.2 months). Blood
      samples were collected for measurement of iPTH, 25-hydroxyvitamin D3, 1,25
      dihydroxyvitamin D3, calcium, albumin, phosphate and creatinine. The eGFR was
      calculated using the formula for the modification of diet in renal disease.
      RESULTS: One hundred and three patients (80%) had an elevated level of iPTH, 29
      (23%) had hypercalcaemia and 42 (35%) had a 25-hydroxyvitamin D3 level of <40
      nmol/L. In stepwise backward regression, eGFR and 25-hydroxyvitamin D3 were
      associated with iPTH, as follows: iPTH = 24.91 -(0.06 x 25-hydroxyvitamin D3) -
      (0.16 x eGFR) (R2 = 0.14). No associations with these two variables were,
      however, detected in patients with an eGFR of >60 ml/min/1.73 m2. Forty patients
      (31%) were transplanted pre-emptively, and the iPTH concentrations were
      significantly lower in these patients. CONCLUSIONS: Decreasing eGFR was the
      single most important variable predicting iPTH level in a cohort of renal
      transplant patients with an eGFR of 30-60 ml/min/1.73 m2, but not in patients
      with an eGFR of >60 ml/min/1.73 m2. Patients transplanted pre-emptively had a
      statistically significantly lower iPTH level compared with patients who had
      received dialysis.

PMID- 18050016
TI  - Endoscopic treatment of massive rectal bleeding following transrectal ultrasound
      guided prostate biopsy.
AB  - Rectal bleeding is frequently seen in patients undergoing transrectal ultrasound
      guided prostate biopsy. This report details a case of life-threatening rectal
      bleeding following this procedure which was successfully treated by means of
      endoscopic sclerotherapy. The aim of this report is to share our experience of
      the management of massive rectal bleeding following prostate biopsy.

PMID- 18050017
TI  - In utero laser treatment of type II vasa previa.
AB  - Vasa previa, defined as fetal vessels coursing within the membranes between the
      presenting part and the cervix, occurs in approximately 1:2500-5000 pregnancies.
      Type II vasa previa consists of fetal vessels crossing over the internal os
      connecting a bilobed placenta or a succenturiate lobe with the main placental
      mass. These vessels are prone to compression during labor or may tear when
      membranes rupture potentially resulting in fetal exsanguination and neonatal
      death. This complication could be avoided altogether if the vessels could be
      obliterated in utero. The purpose of this communication is to report the
      successful in utero laser ablation of type II vasa previa at 22.5 weeks of
      gestation. Subsequent ruptured membranes did not result in untoward fetal
      consequences. Risks and benefits of this novel procedure are discussed.

PMID- 18050018
TI  - Expression of cytokines and chemokines in cervical and amniotic fluid:
      relationship to histological chorioamnionitis.
AB  - OBJECTIVE: To correlate cervical and amniotic fluid cytokines and macrophage
      related chemokines to the development of histological chorioamnionitis (HCA) in
      patients with preterm labor (PTL) and preterm prelabor rupture of the membranes
      (PPROM). STUDY DESIGN: Cervical and amniotic fluid interleukin (IL)-6, IL-8, IL
      18, monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 from pregnant women
      (at <or=34 weeks of gestation) in PTL (N = 42) were analyzed and related to the
      subsequent occurrence of HCA or inflammatory signs in the placenta. For the
      patients with PPROM (N = 30) only amniotic fluid proteins were analyzed. RESULTS:
      Intra-amniotic levels of IL-6, IL-8, IL-18, MCP-1, and MCP-3 were significantly
      higher in PTL cases with HCA compared to non-HCA controls, whereas no such
      relationship was obtained in the PPROM group. Cervical IL-8 and IL-6 (but not IL
      18, MCP-1, MCP-2, and MCP-3) in PTL patients was associated with HCA, and at a
      cut-off level of 10.0 ng/mL cervical IL-8 was a strong predictor of HCA in the
      PTL cases (sensitivity 100%, specificity 67%, positive predictive value 63%,
      negative predictive value 100%). The cytokine and chemokine levels in the group
      with inflammatory signs were generally higher than in controls but lower compared
      to the concentrations in the HCA group. CONCLUSIONS: The amniotic levels of IL-6,
      IL-8, IL-18, and the CC-chemokines MCP-1 and MCP-3 in PTL patients all predicted
      HCA, whereas only IL-8 was a clinically useful marker of HCA in the cervical
      fluid. In addition there is indication that the levels of inflammatory proteins
      are related to the degree of inflammatory infiltration in placental tissue
      samples.

PMID- 18050019
TI  - Obstetrician-gynecologists' knowledge of preterm birth frequency and risk
      factors.
AB  - OBJECTIVES: To assess obstetrician-gynecologists' knowledge of preterm birth,
      including prevalence, risk factors, and utility of various tests in predicting
      increased risk. METHODS: A questionnaire was mailed to 1193 members of the
      American College of Obstetricians and Gynecologists. RESULTS: The response rate
      was 59%. The majority of respondents were familiar with basic preterm birth
      prevalence rates. However, 21% underestimated the proportion of women with
      presumptive preterm labor in whom preterm birth will not occur. The majority
      (55%) overestimated the proportion of preterm births accounted for by multiples.
      Twelve percent indicated bed rest as a proven method for improving newborn
      outcome. Respondents were fairly accurate as to which factors produce the biggest
      increased risk of spontaneous preterm labor or rupture of membranes; however,
      they tended to overestimate the risk associated with smoking, hypertension, and
      non-gestational diabetes. They tended to underestimate, or were unsure of, the
      predictive value of positive fetal fibronectin (fFN) test results or short
      cervical length. CONCLUSIONS: Obstetrician-gynecologists' basic knowledge
      concerning preterm birth prevalence and risk factors was adequate. However, they
      tended to overestimate the risk associated with various maternal factors and
      underestimate the predictive value of various test results.

PMID- 18050020
TI  - Glucose challenge test: screening threshold for gestational diabetes mellitus and
      associated outcomes.
AB  - OBJECTIVE: To examine whether women with an 1-hour 50-g glucose challenge test
      (GCT) for gestational diabetes mellitus (GDM) between 120 and 140 mg/dL and
      >or=140 mg/dL are at risk of perinatal complications. STUDY DESIGN: A
      retrospective cohort study of women with singleton pregnancies screened for GDM
      between 1988 and 2001 with a 1-hour 50-g GCT. Values of GCT were stratified into
      four subgroups: <120, 120-129, 130-139, and >or=140 mg/dL. Perinatal outcomes
      were compared using the Chi-square test and multivariable logistic regression
      analysis. RESULTS: There were 13 901 women meeting the study criteria. Compared
      to women with a GCT of <120 mg/dL, women with a GCT of 130-139 mg/dL and >or=140
      mg/dL were more likely to have preeclampsia and operative vaginal or cesarean
      deliveries. Neonates born to women with a GCT of 130-139 mg/dL also had higher
      odds of having a 5-minute Apgar score <7 (odds ratio (OR) = 1.51, 95% confidence
      interval (CI) 1.01-2.29), shoulder dystocia (OR = 2.02, 95% CI 1.16-2.55), birth
      trauma (OR = 1.47, 95% CI 1.06-2.02), and composite morbidity (OR = 1.25, 95% CI
      1.03-1.51). Women with a GCT of >or=140 mg/dL had higher odds of macrosomia (OR =
      1.32, 95% CI 1.13-1.54) and shoulder dystocia (OR = 1.68, 95% CI 1.11-2.55).
      CONCLUSION: Women with GCT results of 130-139 mg/dL appear to be at increased
      risk for perinatal morbidity. Thus, utilizing a diagnostic test in women with a
      GCT above 130 mg/dL should be considered.

PMID- 18050022
TI  - [Diagnosis of functional voice disorders by using the high speed recording
      technics].
AB  - INTRODUCTION: Malfunctions of the human voice with unknown causes are denoted by
      "functional voice disorders". The high speed video imaging technique (HVT) allows
      the recording of the oscillating vocal folds in real time. A new method is
      presented, describing different types of oscillation and their onset
      mathematically. A precise classification of the kind of functional voice
      disorders is possible. METHODS: For 71 young women, from the HVT recordings two
      parameters were mathematically estimated, reflecting the phonation onset
      dynamics: The threshold value A(th), corresponding with the myoelastic tone of
      the vocal folds and a maximum sound pressure level of speech L(max),
      characterising the efficiency of voice. RESULTS: Both values are sensitive for
      functional voice disorders and enable a differentiation between these
      pathologies. DISCUSSION: Significant differences of the computed parameters
      between the pathological groups and normal voices substantiate the presented
      method as a stable and objective tool for medical diagnosis.

PMID- 18050024
TI  - [Glitazones critically evaluated].

PMID- 18050025
TI  - [Knowledge and experience of palliative medicine among general practitioners in
      Germany].
AB  - BACKGROUND AND OBJECTIVES: Levels of experience and competence in palliative
      medicine vary considerably among physicians. The aim of the study was to collect
      information from specially interested general practitioners on education, pivotal
      lectures and experience regarding the delivery of palliative care. SUBJECT AND
      METHODS: 92 general practitioners (41 women and 22 men) attending a basic course
      in palliative medicine were asked to fill in a standardized questionnaire
      relating to their knowledge and experience of palliative medicine. 63 responded
      (68%), 54 in general private practice, nine worked in a hospital. The same number
      worked in urban and in rural health care facilities. RESULTS: The majority of
      those questioned (53%) gained their first experience in palliative medicine as
      junior hospital doctors about a quarter (26%) only after starting in private
      practice. Many of the doctors (31%) admitted to taking more interest in
      palliative medicine only after having made mistakes, a significant percentage
      (20%) after the death of a relative. 28% expressed the view that practical
      courses were an important part in learning about palliative medicine.
      CONCLUSIONS: The implementation of practice-based c tuition of medical students
      and of continuing education of established general practitioners and hospital
      physicians in palliative medicine is indispensable.

PMID- 18050026
TI  - [Acquired reactive perforating collagenosis associated with diabetes mellitus and
      renal insufficiency requiring dialysis].
AB  - HISTORY: A 60-year-old man with diabetes mellitus and chronic renal insufficiency
      needing hemodialysis was admitted with a 3 months history of multiple
      hyperkeratotic papules on the trunk and extremities partly ulcerated with a
      keratotic central plug. INVESTIGATIONS: Laboratory tests revealed elevated levels
      of blood urea nitrogen, creatinine, and HbA (1c). Histopathology showed vertical
      strands of collagen perforating from the ulcerated lesions. COURSE, DIAGNOSIS AND
      TREATMENT: The biopsy specimen was consistent with acquired reactive perforating
      collagenosis. The progression was stopped and secondary wound healing was
      initiated after two weeks of therapy with allopurinol and PUVA. CONCLUSION:
      Acquired reactive perforating collagenosis should be considered when ulcera with
      oystershell-like keratotic plugs are found especially in patients with
      predisposing diseases like diabetes and renal insufficiency. A good
      interdisciplinary cooperation between internist and dermatologist is crucial for
      the early recognition by histopathology and the immediate treatment.

PMID- 18050027
TI  - [Persistent left superior vena cava].

PMID- 18050028
TI  - [Therapy with glitazones--a risk for cardiovascular disease?].
AB  - INTRODUCTION: Thiazolidinediones significantly reduce fasting plasma glucose and
      HbA (1c). These effects are due to improved insulin sensitivity by activating the
      nuclear PPAR-gamma (peroxisomal proliferator-activated receptors-gamma) and
      affection of different intracellular functions. The objective of this review was
      to analyse recently published studies and meta-analyses about thiazolidinediones,
      which suggested a significant cardiovascular risk associated with rosiglitazone
      therapy. Therefore clinicians have been left uncertain as to whether
      rosiglitazone should still be considered for the treatment of type-2-diabetes.
      DISCUSSION: An important side-effect of thiazolidinediones is fluid retention and
      edema. Therefore, heart failure NYHA I-IV is a contraindication for treatment
      with Thiazolidinediones. Pioglitazone shows favourable changes in lipid
      parameters like decrease of serum-triglycerides and increase of HDL-cholesterol,
      while Rosiglitazone temporarily increases LDL-cholesterol. In patients with type
      2-diabetes mellitus and a high cardiovascular risk the PROactive study did not
      show a significant effect on the primary endpoint but significantly reduced the
      predefined secondary combined endpoint of total mortality, nonfatal myocardial
      infarction and stroke. Conversely, recently published meta-analyses suggested an
      increased cardiovascular risk and myocardial infarction rate associated with
      rosiglitazone therapy. CONCLUSION: Treatment with Rosiglitazone should be
      reconsidered because of a potential cardiovascular risk. In high risk patients
      without heart failure pioglitazone may be favoured for treatment of type 2
      diabetes mellitus.

PMID- 18050029
TI  - [Modern endoscopic procedures for diseases of the respiratory tract].
AB  - Bronchoscopy is the most important diagnostic procedure for the work-up of
      central bronchial processes and parenchymal lung diseases, such as lung cancer,
      pneumonias or diffuse lung diseases. Recent progress - ultrasound, navigation
      systems or ultrathin bronchoscopes - was made to achieve a better yield in the
      diagnosis of peripheral and peribronchial lesions. Bronchial recanalisation by
      thermal ablation or stenting is mainly performed with rigid instruments; these
      procedures as well as brachytherapy in local anaesthesia should be restricted to
      specialized centers. If pleuracentesis does not provide the etiology of pleural
      effusion, thoracoscopy in local anaesthesia is the method of choice. The
      procedure does not only provide a definite diagnosis for almost all of the
      patients, it also allows the immediate option for talcum poudrage in case of
      pleural malignancy.

PMID- 18050030
TI  - [To disclose or not to disclose? Chances and risks of the publication of medical
      quality comparisons].

PMID- 18050031
TI  - [Percutaneous liver biopsy].

PMID- 18050032
TI  - [What happens in the brain of my patients? Neuroimaging and neurogenetics as
      ethical challenges in medicine].
AB  - Precise diagnosis of many neurological or psychiatric diseases has for long been
      one of the main problems in medicine. New diagnostic procedures like neuroimaging
      or neurogenetics seem now able to change thi situation but evoke new ethical
      questions. How should we cope with the fact that we may be able to diagnose and
      even predict diseases like schizophrenia or Alzheimer's Disease? How should we
      deal with incidental findings in neuroimaging? Can and should we use neuroimaging
      or neurogenetic procedures to detect certain behavioral dispositions? A new
      interdisciplinary research programme, called "neuroethics", can provide an
      ethical orientation for such questions.

PMID- 18050033
TI  - [Determining the current position regarding the value of pioglitazone for the
      therapy of diabetes].

PMID- 18050034
TI  - [Dopamine: less important in emergency medicine?].

PMID- 18050035
TI  - Stabler's sign revisited in a spontaneously ruptured neuroblastoma of the
      newborn.
AB  - Retroperitoneal hemorrhage is known to cause bruising of flanks (Turner's sign),
      umbilicus (Cullen's sign), pubis and groin (Stabler's sign), upper thigh (Fox's
      sign), or scrotum (Bryant's sign). Spontaneous adrenal hemorrhage is the most
      common cause of nontraumatic parietal ecchymosis sign in neonates. Only 20 such
      neonatal cases have been reported in the literature. Because all of them were of
      benign etiology, conservative management is generally recommended in the presence
      of this sign. We report the sign for the first time in a case of spontaneously
      ruptured adrenal neuroblastoma of newborn. Perinatal physicians need to be aware
      of this unusual presentation of neonatal neuroblastoma.

PMID- 18050036
TI  - A neonate with microphthalmia and median clefting of the lower lip and mandible.
AB  - Median clefts of the lower lip and mandible are very rare congenital anomalies.
      We report a female infant born to nonconsanguineous parents with unilateral
      microphthalmia and complete median clefting of the lower lip and mandible. This
      uncommon constellation of congenital malformations has never been reported in a
      liveborn infant.

PMID- 18050037
TI  - Effects of repeated courses of antenatal corticosteroids on somatic development
      in children 6 to 10 years of age.
AB  - This study assessed the effects of repeated courses of antenatal corticosteroids
      on biometric characteristics, salivary cortisol, and heart function in children 6
      to 10 years of age using a retrospective cohort study. Twenty-nine children whose
      mothers had received two or more courses of antenatal corticosteroids were
      identified from hospital charts. Eighty-seven children whose mothers did not
      receive antenatal corticosteroids were frequency matched with the exposed group
      by child's age, sex, and ethnicity. The body development, heart function, and
      salivary corticosteroid level were evaluated at 6 to 10 years of age. The
      percentiles of body measurements were calculated based on the 2000 Centers for
      Disease Control and Prevention growth charts. The general linear models were
      applied to assess the observed association. Decreased head circumference (
      P=0.017) and body mass index (BMI) ( P=0.047) in children 6 to 10 years of age
      were associated with repeated courses of antenatal corticosteroids. Morning
      salivary cortisol level was lower in the exposed group than the unexposed group (
      P=0.048). No difference was found in height, weight, blood pressure, heart rate,
      and echocardiogram measurements between the two groups. Repeated courses of
      antenatal corticosteroid therapy are associated with decreased head
      circumference, BMI, and salivary cortisol level in children 6 to 10 years of age.

PMID- 18050038
TI  - [Experience with the G-DRG-system five years after its introduction, as assessed
      by the Society of Pediatric Oncology and Hematology (GPOH)].

PMID- 18050039
TI  - Defining leukemia stem cells in MLL-translocated leukemias: implications for
      novel therapeutic strategies.
AB  - Hematological malignancies and probably many other tumors are dependent on highly
      proliferating and self-renewing cancer stem cells. An important question in the
      development of novel, less toxic antileukemic strategies specifically targeting
      leukemia stem cells is how closely leukemia stem cells are related to normal
      hematopoietic stem cells. It has been recently demonstrated that leukemia stem
      cells can be derived from different stages in normal hematopoiesis and have
      unique phenotypic and genetic features. Introduction of Mixed-lineage leukemia (
      MLL)-fusion oncoproteins, frequently found in infant leukemias and therapy
      related leukemias, into differentiated hematopoietic progenitor cells results in
      the generation of leukemias with a high frequency of leukemia stem cells. The
      progenitor-derived leukemia stem cells ectopically express a limited stem cell
      program while maintaining the global identity of differentiated myeloid cells.
      Development of therapeutic strategies that specifically target the leukemia stem
      cell program while sparing normal hematopoietic stem cells may represent a novel
      therapeutic approach in human leukemias with high efficacy yet less side effects.

PMID- 18050040
TI  - Which clinical and biological tumor markers proved predictive in the prospective
      multicenter trial HIT'91--implications for investigating childhood
      medulloblastoma.
AB  - BACKGROUND: Most recent studies analyzing candidate biological prognostic factors
      in childhood medulloblastoma (MB) are limited by small patient numbers due to
      dependence on fresh-frozen tumor material. By contrast, large archives of
      formalin-fixed, paraffin-embedded MB samples exist from homogeneously treated
      patients. PATIENTS AND METHODS: We have optimized RNA and DNA isolation from
      formalin-fixed paraffin-embedded MB samples. We then analyzed archived tumor
      samples from well-documented patients treated within the prospective randomized
      multicenter trial HIT'91 for DNA amplification of c-myc and N-myc, and mRNA
      expression of c-myc and trkC. RESULTS: TrkC and c-myc mRNA expression were
      identified as independent prognostic factors by multivariate analysis. Three risk
      groups were identified: 1) Favorable risk group: All 8 patients (2 metastatic)
      with elevated trkC and reduced c-myc mRNA expression (compared to levels of human
      cerebellum) remained relapse-free (7-year EFS 100%). 2) Poor risk group: 10 of 15
      patients with metastatic disease and high c-myc and low trkC mRNA expression
      relapsed (7-year EFS 33%). 3) Intermediate risk group: The 7-year EFS of the
      remaining 78 patients was 65%. CONCLUSIONS: While the collection of fresh-frozen
      tumor samples is remaining a major challenge in large clinical trials, routinely
      processed paraffin-embedded tissue samples can be used to quantitate biological
      prognostic factors on the DNA and RNA level. Upon prospective validation of cut
      off levels, this may lead to better risk-based stratification systems for
      children with medulloblastoma.

PMID- 18050042
TI  - First experiences with laparoscopic adjustable gastric banding (LAGB) in the
      treatment of patients with childhood craniopharyngioma and morbid obesity.
AB  - Craniopharyngiomas are embryogenic malformations which lead to eating disorders
      and morbid obesity due to hypothalamic involvement in about 50% of all patients
      with pediatric craniopharyngioma. The experience with laparoscopic adjustable
      gastric banding (LAGB) in obese craniopharyngioma patients is limited. We are
      reporting on four patients with childhood craniopharyngioma diagnosed at age 2,
      11, 12, and 21 years. BMI-SDS at diagnosis was +0.9, +4.5, +4.7 and -0.1 SD.
      During follow-up, all patients developed morbid obesity (BMI-SDS: +13.9, +10.3,
      +11.4, +7.3) so that 11, 6, 9 and 3 years after diagnosis LAGB were performed.
      After a follow-up of 4.5, 1.5, 3.0 and 2.5 years BMI decreased or stabilized
      continuously in all patients (BMI-SDS at latest visit: +9.9, +9.7, +9.5, +5.9
      SD). The eating behavior changed in all patients profoundly. The addiction to
      food and especially sweets significantly improved based on self-assessment. In
      two patients a dislocation of the LAGB occurred and resulted in weight gain. We
      conclude that LAGB could be effective in weight reduction of obese
      craniopharyngioma patients with hypothalamic syndrome. Close follow-up is
      necessary in order to analyze long-term effects and complications of LAGB in
      patients with childhood craniopharyngioma and morbid obesity.

PMID- 18050041
TI  - Serial intense chemotherapy combining topotecan, etoposide, carboplatin and
      cyclophosphamide (TECC) followed by autologous hematopoietic stem cell support in
      patients with high risk soft tissue sarcoma (STS).
AB  - In nine patients (pts) with soft tissue sarcoma refractory to conventional
      therapy (incomplete response or relapse) intensified chemotherapy was
      administered combining 0.75 mg/m (2) topotecan, 100 mg/m (2) etoposide, 100 mg/m
      (2) carboplatin and 200 mg/m (2) cyclophosphamide on day 1-5 (TECC). To avoid
      prolonged intervals between the serial TECC courses autologous hematopoietic stem
      cell supports (median 1.0 x 10(6) CD34+ cells per kg body weight (bw), range 0.5
      2.8 x 10(6) CD34+ cells/kg bw, SD 0.6 x 10(6) CD34+ cells/kg bw) were given on
      day 7. All pts received granulocyte colony stimulating factor (GCSF) from day 8
      in addition. All together 39 TECC courses (minimum 2 courses, maximum 6 courses
      per pt) were administered, with a median interval of 32 (range 21-52) days until
      recovery. Leukopenia (<1000/microl) occurred 9 days (range 3-13 days; SD 2.4
      days) after end of chemotherapy and persisted for 9 (range 3-15 days; SD 3 days)
      days. In 31/39 TECC courses readmission to hospital was required for supportive
      therapy mainly due to neutropenic fever. In this period pts received 0.83 (range
      0-1) red blood cell units and 2.35 (range 1-4) platelet units. C-reactive protein
      in neutropenic pts as an indicator for infection after TECC chemotherapy was
      detectable after 36 of 39 chemotherapy courses leading to further supportive
      therapy (median 10.4 mg/dl, range 1.1-28.3 mg/dl; SD 6.67 mg/dl). Duration of
      total inpatient treatment per TECC course including supportive therapy was in
      median 13.5 days (range 7-53 days; SD 4.3 days). Only two children had a
      prolonged infection (77 and 100 days). Clinical and objective tumor responses,
      defined as complete remission, very good partial response and partial response
      were observed in 9/9 pts at eight weeks after the last TECC course and were
      maintained at six months in 7/9 pts. Median time to progression and median
      overall survival time after TECC chemotherapy were 20.3 months and 25.2 months,
      respectively. These data provide evidence that in very high risk pts refractory
      to standard high risk therapy, a combination of TECC chemotherapy and stem cell
      support is feasible in pts with incomplete remission respectively relapsed STS
      pts and demonstrates promising antineoplastic activity. Therefore, this regimen
      warrants further investigation in prospective trials.

PMID- 18050043
TI  - [Results of an endocrinological follow-up of patients with childhood-or
      adolescent-onset malignancies].
AB  - BACKGROUND: Established reports about endocrine follow-ups in children and
      adolescents with cancer were rare. PATIENTS: 53 children were included in the
      clinical trial. The mean age was 9.6 years (0.5; 17.2 years), 10 patients died
      within the study period. The mean body length was normal with -0.14 SDS (-2.3;
      2.5 SDS), as well as the body weight with 0.01 SDS and BMI with a mean of -0.03
      SDS. Children and adolescents with different types of malignant tumors were
      included. According to the therapy protocol or tumor entity we divided this
      population in 5 subgroups (group 1 leukemia with 17 patients, group 2 lymphoma
      with 11 patients, group 3 tumor of CNS with 10 patients, group 4 bone and soft
      tissue tumors with 8 patients, group 5 different tumors with 7 patients). METHOD:
      Anthropometrical and laboratory parameters were analyzed in intervals of 6 months
      over 2 years from the time point of diagnosis. RESULTS: We found differences in
      body height in children affected by cerebral tumors at the time of diagnosis and
      therefore before any therapy was started. These patients were significantly
      shorter (-0.6 SDS) than the other children. The body weight increased within the
      first year of therapy and was still higher than normal in the second year
      (comparison at the time point; from start to the first year+0.5 SDS, to second
      year+0.4 SDS) independently from the cortisone administration. Moreover,
      significant differences in the growth factor concentrations between the groups
      and time points were identified. Interestingly, children who survived their
      malignant disease tended to have higher levels of IGF-I and IGFBP-3 concentration
      than the patients who died within the study period. Additionally, the thyroid
      function was affected, shown as an increase of TSH with a concomitant decrease of
      the free thyroxin in 91% of all patients independent from the diagnosis (start
      TSH 1.8, fT4 15.6, after first year TSH 2.8, fT4 15.0). Thyroid function was
      monitored in 12 children, in 5 patients a short- or long-term substitution with
      thyroid hormone was indicated. Endocrine testing was initiated in 4 children, in
      2 patients affection of the adrenal gland could be excluded, a suspected
      pituitary dysfunction after radiation was confirmed in 2 patients. CONCLUSION: We
      could represent that children and adolescents with malignant diseases showed
      affection of the endocrine system due to the tumour and the intensive therapy.
      The dysregulations in the endocrine system can be diagnosed through closely
      spaced monitoring and interdisciplinary cooperation.

PMID- 18050044
TI  - From neonates to adolescents--the diagnostic significance of pitted erythrocytes
      in hyposplenic and asplenic children.
AB  - BACKGROUND: Splenic function may be reduced or absent in a range of medical
      conditions in childhood, most prominently in homozygous sickle cell disease,
      celiac disease, or after total or partial splenectomy. In neonates and patients
      with malignant disease, transient hyposplenia has been reported as well. A simple
      method with reliable reference values is required to determine a patient's
      splenic function and thereby assess the risk of systemic infection. PATIENTS:
      Pitted erythrocytes (pitE) were determined semi-quantitatively in patients up to
      20 years of age. This included splenectomized individuals, patients at risk for
      hyposplenia (homozygous sickle cell anemia (HbSS), leukemia, nephroblastoma and
      Hodgkin's disease after irradiation, patients after stem cell transplantation
      (SCT)), term and preterm neonates, and 90 controls (0-20 years of age, no
      neonates). METHOD: A capillary blood sample was diluted in buffered
      glutaraldehyde. PitE were scored using differential interference contrast
      microscopy with Nomarski optics. RESULTS: PitE were <2% in all controls
      regardless of age, in splenectomized individuals >18%. In patients with HbSS,
      pitE scores ranged from 6.2 to 44%. Scores did not exceed 2% in patients after
      SCT, irradiation, or during chemotherapy for leukaemia. In term neonates, pitE
      were increased in the perinatal period only. The elevation in preterm neonates
      persisted up to 2 months after birth. CONCLUSION: Serial measurement of pitE can
      be used to accurately and reliably assess splenic function in children. Except
      for neonates, pitE are consistently <2% in healthy individuals. For clinical
      purposes, the degree of hyposplenia can be determined to give an estimation of
      the risk of severe infection, e.g. in patients with HbSS or after partial
      splenectomy.

PMID- 18050045
TI  - Severe combined immunodeficiency signalized by eosinophilia and lymphopenia in
      rotavirus infected infants.
AB  - BACKGROUND: Severe combined immunodeficiency (SCID) is a heterogeneous disease
      consisting of several different subtypes. Most subtypes present during infancy
      and without treatment, infections usually lead to early death. Diagnosis of SCID
      can be difficult as new subtypes are expected to be discovered soon. Late
      diagnosis is associated with a poorer outcome. Infections like rotavirus
      enteritis cannot be cleared in children with SCID due to impaired immunity. The
      aim of our study was to identify clues in children with rotavirus enteritis that
      aid to diagnose SCID early. PATIENTS AND METHODS: Total white blood counts in a
      cohort of SCID patients with persistent rotavirus infection at diagnosis (n=18)
      were compared to total white blood counts in matched control patients without
      SCID but with rotavirus infection. RESULTS: Relative and absolute lymphopenia and
      eosinophilia were more common in SCID patients (p<0.005). CONCLUSION: In infants
      with rotavirus infection, a full blood count should be performed: Eosinophilia
      and/or lymphopenia raise a high suspicion of SCID.

PMID- 18050046
TI  - [Wegener's granulomatosis in pediatric patients].
AB  - Wegener's Granulomatosis (WG) is a disease occurring rarely in childhood and
      adolescence. Together with the Churg-Strauss-Syndrome and the microscopic
      Polyangiitis it belongs to the vasculitis syndromes associated with ANCA. WG
      mostly affects the upper and lower respiratory tract and kidneys. It is
      characterized by a chronic development and high tendency to relapse. In cases of
      persistent disturbances of the respiratory system which do not have infectious or
      allergic geneses differential diagnosis should also consider WG. Although
      clinical course and prognosis have improved since the introduction of
      immunosuppressive therapy, WG, leading to renal failure in about one third of all
      cases, remains a disease which has to be taken seriously. Early treatment has
      been proven to improve prognosis. Due to the necessity of longterm treatment less
      toxic immunosuppressive therapy should be applied (e.g. Methotrexate).

PMID- 18050047
TI  - Diphtheria (D) and tetanus (T) antibody values in children with acute
      lymphoblastic leukaemia (ALL) after treatment according to Co-ALL 05/92.
AB  - BACKGROUND: Children and adolescents after acute lymphoblastic leukemia are at
      risk for a prolonged period of immunodeficiency. Normally within 6 to 9 months
      after the end of maintenance treatment an adequate immune recovery is present.
      Factors such as immunity against specific antigens prior to disease (applied
      baseline vaccination), intensity of treatment and age can play a role in the
      appearance of antibodies in serum. Diphtheria (D) and Tetanus (T) antibodies are
      known to appear within 3 to 6 months after end of treatment as a sign of immune
      recovery and the reinstatement of immunological memory. A number of different
      questions are of interest: What differences are seen in the antibodies to D and T
      in children of different ages after treatment with a standardized protocol? What
      is the influence of post-treatment revaccination with Diphtheria/Tetanus (D/T)
      and treatment group on the production of D/T antibodies? PATIENTS AND METHODS:
      Out of 142 children and adolescents until the age of 16, treated according to the
      Co-ALL 05/92 protocol, 59 patients were eligible for evaluation: 31 Low-Risk (LR)
      and 28 High-Risk (HR) patients. Antibodies against Diphtheria (D) and Tetanus
      (T) were measured 3-12 months after the end of treatment and after revaccination
      in case of low antibody levels against D and/or T. In patients without adequate
      response after repeated revaccination the cellular immunity was examined with a
      skin test. RESULTS: After the end of treatment, children in the low-risk (LR)
      group showed more frequently adequate antibody titres against D and T than
      children of the high-risk (HR)-group. Antibodies against T were present in 50% of
      all patients. After revaccination antibodies against T were found in nearly all
      patients whereas for D this is only the case in some children. Patients without
      sufficient antibody levels mainly showed an adequate cellular immunity.
      CONCLUSION: In children and adolescents with ALL after therapy antibody levels of
      D and T are dependent on treatment intensity. Revaccination leads to an adequate
      immunological answer against T in most patients , which is not the case for the
      diphtheria vaccination. Prospective multicenter trials starting together with the
      ALL-treatment should be able to gain more information about the behavior of
      antibody levels and the risk of infection from vaccine-preventable disease in
      immunocompromised patients and thus lead to standardized vaccination guidelines
      such as immunization with conjugate vaccines already during maintenance
      treatment.

PMID- 18050049
TI  - [Position paper by the Gesellschaft fur Padiatrische Onkologie und Hamatologie
      (GPOH) and the Deutsche Leukamie-Forschungshilfe (DLFH) on psycho-social care for
      pediatric oncology and hematology patients in hospital].
AB  - Psychosocial Care has been an integral part of the overall treatment in pediatric
      oncology for 25 years. The need for it and its effectiveness are well documented
      in several reputable studies and psychosocial service has proved its worth in
      everyday clinical settings. In order to secure comparable quality standards and
      in consequence of reorganisations within the health-care system a position paper
      has been prepared and adopted by the Psychosoziale Arbeitsgemeinschaft in der
      Padiatrischen Onkologie und Hamatologie (PSAPOH), the Gesellschaft fur
      Padiatrische Onkologie und Hamatologie (GPOH) and the Deutsche Leukamie
      Forschungshilfe (DLFH). The following article gives a short survey of this
      position paper and provides insight into the goals, conditions and outcomes of
      psychosocial care in pediatric oncology and hematology.

PMID- 18050048
TI  - [A rare inborn error of intracellular processing of cobalamine presenting with
      microcephalus and megaloblastic anemia: a report of 3 children].
AB  - INTRODUCTION: Defects of methionine synthase or methionine synthase reductase
      result in an impaired remethylation of homocysteine to methionine. Patients
      present with megaloblastic anemia, failure to thrive and various neurological
      manifestations including mental retardation, cerebral atrophy, muscular hypotonia
      or hypertonia, ataxia, seizures, nystagmus and visual disturbances. PATIENTS: We
      report on three children (two girls, one boy), aged 3.5-7.5 years, who presented
      with severe megaloblastic anemia, micro-cephalus and partly nystagmus (2/3) due
      to a rare inborn error of remethylation. RESULTS: Methionine synthase reductase
      deficiency, cblE type of homocystinuria (OMIM 236270), is a rare autosomal
      recessive inherited disorder described only in 14 patients worldwide. Metabolic
      hallmarks of the disease are hyperhomocysteinemia (median 98 micromol/l, normal
      range <15) without methylmalonic aciduria but often hypomethioninemia. The
      patients described here were diagnosed at ages of 2-18 months. The importance of
      an early recognition of this possibly underdiagnosed congenital disease is
      stressed. Treatment consisted of the application of hydroxocobalamine (1-2 mg
      weekly, i.m.), betaine (100-200 mg/kg daily, p.o.), folate (5-10 mg daily, p.o.)
      and intensive physical therapy. CONCLUSION: Defects of intracellular processing
      of cobalamine must be considered in all patients with neurological symptoms in
      combination with megaloblastic anemia. Measurements of homocysteine and
      methionine in plasma as well as methylmalonic acid in urine is required for
      confirming the diagnosis. Early treatment im-proves the outcome, although mental
      disability may not be prevented. Treatment has a positive impact on megaloblastic
      anemia but only slight effect on hyperhomocysteinemia. The long-term
      cardiovascular risk of hyperhomocysteinemia in cblE deficient patients is not
      known yet.

PMID- 18050050
TI  - [Diagnostic and differential-diagnostic considerations regarding the assessment
      of children's reactions within the scope of psychosocial care in paediatric
      oncology and haematology].
AB  - Oncological diseases in children and adolescents represent a considerable burden
      for the children themselves and for their families. In order to position such
      concomitants of a life-threatening disease appropriately among the diagnostic
      options of psychosocial cancer care one is repeatedly confronted with the issue
      of giving a diagnosis from the area of reactions to burdens and adaptive
      disturbances (ICD 10: F: 43 ff). This touches the question of whether or not
      confronting a life-threatening disease in and by itself suffices to fully justify
      establishing one of the psychiatric diagnoses mentioned, which would imply that
      the intensity of the burden experienced justified the assumption of a psychiatric
      disturbance in the person affected. Whereas considerable effort is regularly
      spent on taking action and giving support and care, and reactions occasionally
      exceed the appropriate degree, a fair majority show no pathological processes
      that would justify determining a psychiatric diagnosis as a rule. Ultimately, one
      would arrive at a false interpretation of actually altogether adequate reactions
      of the patient to the burden. The ICD and DSM classification systems, however, do
      not provide for diagnoses other than those allocated disease status; it must
      therefore be considered whether it may be better in these cases to speak not of a
      reaction to a burden or an adaptive disturbance in the sense of the ICD 10,
      Section F, but rather of a sustained reaction to a burden. This opinion is
      increasingly gaining acceptance in pediatric oncology.

PMID- 18050053
TI  - Moment-knee angle relation in well trained athletes.
AB  - The purpose of this work was to investigate whether different modes of long-term
      competitive physical activity cause functional differences in the moment-knee
      angle relation of the M. quadriceps femoris (QF). Therefore, a sample (n = 40) of
      young male competitive endurance runners, cyclists, triathletes and tennis
      players performed isometric maximal voluntary knee extensions (MVC) with their
      stronger leg at six different knee joint angles while keeping the hip joint angle
      constant. Muscle activation of QF-muscles during MVC was estimated using surface
      electromyography (EMG). Moments and EMG data of each subject were normalized to
      the largest value produced at any knee joint position [% Max.]. No significant
      differences in the normalized [% Max.] moment-knee angle relation of the QF were
      found between endurance runners, cyclists and triathletes. Despite few
      unsystematic exceptions, no functional differences in the normalized moment-knee
      angle relation of the QF occurred among tennis players and the endurance-oriented
      athletic groups. Obtained by curve fitting, the optimal knee joint angle for
      moment production was not significantly different among all athletic groups. We
      conclude that long-term competitive endurance running, cycling, triathlon and
      tennis do not provoke functional differences in the moment-knee angle relation of
      the whole QF.

PMID- 18050051
TI  - [Assessment of staffing and infrastructures of paediatric oncology and
      haematology centres in Germany].
AB  - BACKGROUND AND METHODS: At the end of 2003, the Competence Network Paediatric
      Oncology and Haematology conducted a survey of paediatric oncology centres in
      Germany as one of its measures to support and advance the collaboration of
      paediatric oncology centres and trials in science and health care. There was a
      lack of key figures to describe their combined position in the health care
      system. The survey aimed to quantify existing structures in terms of personnel,
      facilities, and patients as well as to collect preliminary information on
      patterns of care and on quality assurance. Starting with the largest patient
      numbers, 53 German centres were included, which cared for at least 10 patients
      under the age of 15 years with a newly diagnosed malignant disease per year. MAIN
      RESULTS: 49 (92%) centres contributed to the survey. 40 centres cared for a total
      of 1712 patients under the age of 15 years with a first occurrence of a malignant
      disease, which corresponds to 83% of all such patients registered in the German
      Childhood Cancer Registry in 2003. The total number of patients cared for in
      these centers, which also includes those with a relapse and the above 15-year
      olds, exceeds the Registry numbers by about 50%. The survey's outcome on staffing
      revealed about two work positions per bed (in-patient or day-clinic). A
      significant part of this personnel is financed by third-party funds. On average,
      the centres responding to the survey were equipped with 7 physician, 21 nursing
      and 4,4 psychologist, social worker, medical documentarist, and secretariat posts
      to care for a mean of 54 patients or 18 in-patient beds. Including those working
      positions financed by third-party funds, the majority of centres scored staffing
      as good or excellent. Yet, one out of ten centres scored the staffing of one or
      more occupational groups as poor. CONCLUSIONS: The survey provided for the first
      time a national assessment of the variable levels of staffing and facilities in
      the most relevant German paediatric oncology centres. The data indicate that the
      relationship between several key figures such as the Registry patient subset's
      numbers and in-patient bed numbers, for example, is weak, whereas physician post
      numbers, for example, correlate reasonably well with actual patient numbers.
      Further data include the variety of special health care offered and preliminary
      provisions for quality assurance per centre. According to a comparison with a
      seminal publication on needs in German paediatric oncology health care published
      in 1991 and with a needs survey of the UK National Institute for Health and
      Clinical Excellence (NICE), there seems to be an insufficient response to the
      needs, which is undermined by the centres survey responses. In view of the DRG
      reimbursement system being introduced throughout German health care, future
      surveys should also focus on key figures related to the DRG system such as case
      numbers, but such data should be merged with patient data in order to maintain a
      perspective on the course of health care provision to children and young adults
      with cancer.

PMID- 18050054
TI  - Effect of regular exercise on senile dementia patients.
AB  - Dementia population worldwide is considerable in elderly people. Exercise
      regulates the brain function, but the mechanism by which it does so is unknown.
      The effect of regular exercise on cognitive function and exercise capacity in
      senile dementia patients was investigated. Thirty female patients with senile
      dementia who participated in the study were divided into two groups: the exercise
      group (EG, n = 15) and the control group (CG, n = 15). The exercise group
      completed a regular exercise program, and their cognitive function, activities of
      daily living and exercise capacity levels were evaluated at baseline, 6 months
      and after 12 months. Subjects exercised 30 - 60 minutes per day, 2 - 3 times per
      week for 12 months. Mini-mental state examination (MMSE) (pre: 14.53 +/- 5.34,
      post: 17.47 +/- 6.90) and ADL (pre: 14.40 +/- 5.32, post: 17.53 +/- 5.46) scores
      were significantly enhanced in the exercise group with senile dementia, compared
      to those in the control group. Exercise capacities such as cardiopulmonary
      function (pre: 128.47 +/- 55.43, post: 184.40 +/- 41.16), muscle strength (pre:
      10.07 +/- 3.61, post: 13.7 +/- 3.90), muscular endurance (pre: 8.13 +/- 4.45,
      post: 12.13 +/- 5.14), flexibility (- 1.53 +/- .30, post: 2.20 +/- .70, balance
      (pre: 1.73 +/- .28, post: 1.20 +/- .77), and agility (pre: 21.80 +/- 3.24, post:
      10.87 +/- 2.99) also increased in the exercise group. Our findings showed that
      regular exercise can enhance cognitive and functional activity scores in dementia
      patients, suggesting that senile dementia may improve by participating in a
      regular exercise program.

PMID- 18050055
TI  - Reliability of power output during dynamic cycling.
AB  - The aims of the present study were to determine the influence of familiarization
      on the reliability of power output during a dynamic 30-km cycling trial and to
      determine the test-retest reliability following a 6-week period. Nine trained
      male cyclists performed five self-paced 30-km cycling trials, which contained
      three 250-m sprints and three 1-km sprints. The first three of these trials were
      performed in consecutive weeks (Week 1, Week 2 and Week 3), while the latter two
      trials were consecutively conducted 6 wk following (Week 9 and Week 10). Subjects
      were instructed to complete each sprint, as well as the entire trial in the least
      time possible. Reproducibility in average power output over the entire 30-km
      trial for Week 2 and 3 alone (coefficient of variation, CV = 2.4 %, intra-class
      correlation coefficient, ICC = 0.93) was better than for Week 1 and 2 (CV = 5.5
      %, ICC = 0.77) and Week 9 and 10 alone (CV = 5.3 %, ICC = 0.57). These results
      indicate that high reliability during a dynamic 30-km cycling trial may be
      obtained after a single familiarization trial when subsequent trials are
      performed within 7 days. However, if cyclists do not perform trials for six
      weeks, the same level of reliability is not maintained.

PMID- 18050056
TI  - MMP-2, jumping exercise and nandrolone in skeletal muscle.
AB  - Matrix metalloproteinases (MMPs) are crucial to the development and maintenance
      of healthy tissue. The aim of this study was to investigate MMP-2 activity in
      gastrocnemius, soleus, extensor digitorium longus (EDL) and tibialis anterior
      (TA) muscles after exercise associated with an anabolic androgenic steroid (AAS).
      Wistar rats were grouped into: sedentary (S); sedentary with AAS (AAS); trained
      without (T) and with (AAST) AAS. Exercised groups performed a 7-week water
      jumping program. The exercise increased MMP-2 activity in gastrocnemius and
      soleus, but not in TA and EDL. The AAS treatment decreased MMP-2 activity of EDL,
      as compared to the S group, with no effect in gastrocnemius and soleus. The
      association of AAS and training restored the normal MMP activity of EDL. Training
      increases tissue turnover in primary motor muscles, which in turn respond
      differently to AAS treatment. This data may be useful for a better understanding
      of muscular physiology under AAS use.

PMID- 18050057
TI  - Discrimination of recombinant and endogenous urinary erythropoietin by
      calculating relative mobility values from SDS gels.
AB  - Erythropoietin (EPO) promotes the production of red blood cells, the key factor
      in the regulation of the oxygen transport, and has been abused by athletes for
      performance enhancement in endurance sports. Current methods to detect EPO misuse
      are based on isoelectric focussing (IEF), double blotting, and chemiluminescence
      detection. A new approach utilizing SDS-PAGE mobilities of target analytes is
      presented. Employing two internal standards (novel erythropoiesis stimulating
      protein and recombinant rat EPO), the assay provides a tool which allows the
      calculation of relative mobility values for endogenous urinary EPO and
      recombinant epoetins (e.g., Dynepo) and, thus, the distinction of these analytes
      in doping control samples. A reference group of 53 healthy volunteers and samples
      originating from a Dynepo (epoetin delta) excretion study conducted with a single
      person were analyzed and led to a significant discrimination of endogenous
      urinary and recombinant EPO. A clear differentiation was accomplished over a
      period of four days post-administration of a single injection of 50 IU/kg body
      weight. Hence, the method may be useful as a screening procedure in doping
      control or as complementary confirmation tool to the established IEF assay.

PMID- 18050058
TI  - Cardiac autonomic responses to standing up and cognitive task in overtrained
      athletes.
AB  - This study compared the autonomic responses to an active orthostatic test and
      Stroop Color Word Test (Stroop) as well as cognitive performance in Stroop in
      twelve severely overtrained (OA, 6 men and 6 women) and twelve control athletes
      (CA, 6 men and 6 women). RR-intervals were recorded during the orthostatic test,
      the Stroop, and a relaxation period succeeding the Stroop. Low frequency power
      during standing in the orthostatic test was lower in OA than in CA (1322 +/- 955
      ms2 vs. 2262 +/- 1029 ms2, p = 0.030, respectively). During Stroop, OA had higher
      relative total power (50 +/- 47 % vs. 19 +/- 14 % of the individual total power
      during supine rest after awakening, p = 0.028, respectively) and high frequency
      power (38.5 +/- 9.4 % vs. 13.5 +/- 2.3 % of the individual high frequency power
      during supine rest after awakening, p = 0.035, respectively) than CA. In the
      Stroop, OA made more mistakes than CA (9.7 +/- 6.5 % vs. 5.4 +/- 3.0 %, p =
      0.045). The increase in absolute total power from the Stroop to relaxation
      correlated negatively with the amount of mistakes in the Stroop (r = - 0.588, p =
      0.003). Thus, cardiac autonomic modulation during orthostatic task and responses
      to cognitive task and to relaxation, as well as the cognitive performance were
      attenuated in severe overtraining.

PMID- 18050059
TI  - Seasonal variation of red blood cell variables in physically inactive men:
      effects of strength training.
AB  - The purpose of this study was to investigate if strength training affects red
      blood cell variables in physically inactive men when taking into account seasonal
      variations. Seventy-four men aged 20-45 were randomly assigned to training (n =
      52) and control (n = 22) groups. Training group underwent 20-week progressive
      strength training. Body composition and maximal voluntary contraction (MVC)
      during knee extension were measured before and after intervention. Fasting blood
      samples were analysed for haematocrit (Hct), count of red blood cells (RBC),
      haemoglobin (Hb), mean cell haemoglobin concentration (MCHC), and mean cell
      volume (MCV) at baseline, 10-week and 20-week follow-up. MVC and lean body mass
      increased in the training group. Hct, Hb and MCHC showed seasonal variation in
      the control group. The training group increased their Hct from 44.7 +/- 2.6 % to
      45.4 +/- 2.5 % (p = 0.026) while the control group decreased their Hct from 44.3
      +/- 2.2 % to 43.1 +/- 2.6 % (p = 0.037) after 20-week intervention. By contrast
      to the control group, the training group increased their Hct (p = 0.001), RBC (p
      = 0.005) and decreased their MCHC (p < 0.001) from 10-week to 20-week follow-up.
      We concluded that strength training could affect seasonal variation patterns of
      red cell variables. Unlike "sport anaemia" induced by endurance training, 20-week
      strength training elevated Hct.

PMID- 18050060
TI  - Hip abductor weakness is not the cause for iliotibial band syndrome.
AB  - Muscular deficits in the hip abductors are presumed to be a major factor in the
      development of Iliotibial Band Syndrome in runners. No definite relationship
      between muscular weakness of the hip abductors and the development of Iliotibial
      Band Syndrome or different ratios between hip adduction to abduction have been
      reported so far. Isokinetic measurements were taken from 10 healthy runners and
      10 runners with Iliotibial Band Syndrome. Primary outcome variables were
      concentric, eccentric, and isometric peak torque of the hip abductors and
      adductors at 30 degrees/s, and a concentric endurance quotient at the same angle
      velocity. Differences in muscle strength of the hip abductors between healthy
      (CO) and injured runners (ITBS) were not statistically significant in any of the
      muscle functions tested. Both groups showed the same strength differences between
      hip adduction and abduction, and increased strength in hip adduction. Weakness of
      hip abductors does not seem to play a role in the etiology of Iliotibial Band
      Syndrome in runners, since dynamic and static strength measurements did not
      differ between groups, and differences between hip abduction and adduction were
      the same. Strengthening of hip abductors seems to have little effect on the
      prevention of Iliotibial Band Syndrome in runners.

PMID- 18050061
TI  - Different diagnostic tools in nonfunctional overreaching.
AB  - The current diagnosis of overreaching and overtraining is based on exclusion. In
      the present paper, four possible confirmative tools have been examined in three
      female speed skaters between 16 and 19 years old. A nonfunctional overreached
      (NFO) athlete, an athlete who was recovering from NFO and a healthy athlete were
      examined. The NFO athlete showed high stress and low regeneration levels at the
      Recovery Stress Questionnaire for Athletes. The recovering athlete showed a more
      favorable profile, although she still showed higher stress and lower recovery
      than the control athlete. On the Profile of Mood States, the NFO athlete showed
      an unfavorable profile. The control athlete showed the typical iceberg profile.
      The recovering athlete showed a profile similar to sedentary individuals. Results
      on a reaction time task showed decreased performance under pressure for the NFO
      but not for the control and the recovering athlete. Hormonal reactions to two
      maximal exercise bouts also differed between the three subjects with an
      overreaction after the second exercise bout of the NFO athlete as the most
      remarkable finding. The Recovery Stress Questionnaire for Athletes, reaction
      times and hormonal reactions to exercise showed to be possible tools that can be
      used in the diagnostic procedure.

PMID- 18050062
TI  - Tibial wedge osteotomy for osteochondral transplantation in talar lesions.
AB  - Between 1999 and 2002, 16 patients with osteochondral lesions on the central and
      posterior talar dome underwent osteochondral autografting. A new approach with
      temporary removal and replacement of a tibial bone block from the anterior tibial
      plafond was adopted. Inclusion criteria were joint stability, an age between 18
      and 50 years, and osteochondral lesions stages 3 and 4 according to the
      radiological classification of Loomer, for which previous arthroscopic treatment
      was not successful. All patients underwent clinical and MRI evaluation after 12,
      35 and 59 months. The AOFAS Ankle Hindfoot score improved significantly between
      the preoperative period and 1 year (p < 0.001), between 1 and 3 years (p <
      0.001), but not between 3 and 5 years postoperative (p = 0.37). The score was
      independent from patients gender (p = 0.44) and age. The Spearman coefficient of
      correlation between clinical outcome and defect size was - 0.79 (p = 0.01),
      indicating that patients with small lesions had the best results. Control
      radiographs and MRIs showed no reduced joint space and good integration of the
      tibial bone block without incongruency. Osteochondral grafting with temporary
      removal of a tibial bone block is a successful technique with good midterm
      results in osteochondral talar lesions for which arthroscopic excision, curettage
      and drilling has failed.

PMID- 18050063
TI  - Psychological effects of music tempi during exercise.
AB  - The purpose of this study was to investigate the effects of music tempi on music
      preference, intrinsic motivation, and flow during long-duration exercise
      (approximately 26 min). Subjects (n = 29) selected the music of a single artist
      then walked at 70 % of maximum heart rate reserve (maxHRR) on a treadmill under
      three experimental conditions (medium tempi, fast tempi, and mixed tempi) and a
      no-music control. A music preference item, the Intrinsic Motivation Inventory,
      and Flow State Scale-2 were completed after each trial. Data were analyzed using
      a mixed-model (Gender x Condition) ANOVA and MANOVA. The Gender x Condition
      interaction was nonsignificant in both analyses (p > 0.05). Contrary to
      expectations, higher preference scores were recorded for medium tempi than for
      mixed tempi (means: 7.8 +/- 1.3 vs. 7.1 +/- 1.1). The medium tempi music also
      yielded the highest levels of intrinsic motivation (p < 0.001). Pairwise
      comparisons showed that interest-enjoyment was higher for medium tempi when
      compared to mixed tempi, 95% CI = 1.80-8.48, p = 0.001, and that each of the
      music preference experimental conditions yielded higher scores than the no-music
      control. Also, pressure-tension was lower for medium tempi compared to fast
      tempi, 95% CI = -3.44-0.19, p = 0.022, and for both medium and mixed tempi
      compared to control (95% CI = -5.33-2.89, p = 0.000; 95% CI = -4.24 - 0.64, p =
      0.004). A main effect was found for global flow (p = 0.000) with the highest mean
      score evident in the medium tempi condition (14.6 +/- 1.5). Follow-up comparisons
      indicated that the medium tempi condition yielded higher flow scores than the
      control, 95% CI = 1.25-3.60, p = 0.000, as did fast tempi, 95% CI = 0.89-3.14, p
      = 0.000, and mixed tempi, 95% CI = 1.36-3.76, p = 0.000. It was concluded that a
      medium tempi music program was the most appropriate for an exercise intensity of
      70% maxHRR.

PMID- 18050064
TI  - Cerebrospinal fluid and serum chitotriosidase levels in patients with aneurysmal
      subarachnoid haemorrhage: preliminary results.
AB  - AIM: The purpose of this study was to investigate the time course(s) of the
      cerebrospinal fluid and serum chitotriosidase changes in patients with aneurysmal
      subarachnoid hemorrhage and to show whether cerebrospinal fluid and/or serum
      chitotriosidase levels might be used as a specific marker for disease severity.
      MATERIAL AND METHODS: Chitotriosidase in the cerebrospinal fluid and serum was
      measured within the first 3 days, at Day 5 and at Day 7 after aneurysmal
      subarachnoid hemorrhage in 20 patients, and the results were compared to 8
      patients with normotensive hydrocephalus. RESULTS: Mean cerebrospinal fluid
      chitotriosidase levels were found to be higher on days 5 and 7 of subarachnoid
      hemorrhage and the serum levels were always higher than controls at all times in
      subarachnoid hemorrhage patients. However, no relationship was found between
      elevated chitotriosidase levels and the clinical parameters including symptomatic
      vasospasm and outcome at 6 months. CONCLUSION: Results indicate that
      chitotriosidase is elevated in the acute stages of subarachnoid hemorrhage but is
      not a specific marker of subarachnoid hemorrhage severity.

PMID- 18050065
TI  - Simulation of cerebrovascular circulation in the human cadaver for surgical
      neuroanatomy training.
AB  - OBJECTIVE: The current progress in diagnostic and screening methods and surgical
      equipment technologies facilitates the accessibility to numerous anatomic
      structures through various interventional approaches. Consequently, the exact
      knowledge of the anatomic locations of neurovascular structures and their
      interactions may ensure that the surgical intervention is planned in the most
      appropriate way and the structures are accessed with the least complication risk
      during the intervention. MATERIAL AND METHODS: A decapitated and formalin fixated
      whole-head of a male human cadaver kept for educational and research purposes in
      the Dokuz Eylul University Department of Anatomy was used in this study. Two
      separate reservoirs (for the arterial and the venous system) were connected to
      the Truno System 3 labeled perfusion pump. The reservoirs were filled with blue
      and red warm tap water. Colored tap water pumped on the right was emptied from
      the left. Continuous flow of the water in the closed-circuit arterial and venous
      systems was achieved. As the circulation was continuing, pterional craniotomy was
      performed and the dura mater was accessed and lifted under the Zeiss dissecting
      microscope. CONCLUSION: We believe that this model may contribute to neuroanatomy
      education and provide experience for the safe and ethical performance of surgical
      interventions during the intraoperative period.

PMID- 18050066
TI  - Spontaneously resorbed idiopathic syringomyelia: a case report.
AB  - A 28-year-old female patient presented with severe neck and back pain in 2003. No
      abnormality was observed at neurological examination. Syringomyelia in the
      cervical region was determined at MRI. MRI examination of the cranial, thoracal
      and lumbosacral regions was normal. The patient refused surgery and was followed
      up. A control cervical MRI 17 months later showed that the syringomyelia had
      disappeared. This spontaneously resorbed case of idiopathic syringomyelia,
      presenting solely due to neck and back pain and with a normal neurological
      examination, was evaluated in the light of syringomyelia pathogenesis as only
      three similar cases have been identified in the literature.

PMID- 18050067
TI  - Familial syringomyelia in two siblings: case report.
AB  - We report on syringomyelia of the thoracic spinal cord in two sisters without a
      Chiari or any other malformation. In both cases syringomyelia was determined by
      magnetic resonance imaging (MRI). Spinal MRI showed a syringomyelia between T6-T8
      levels in the first sibling and between T7- T9 in the second sibling. The cranio
      cervical junction was normal and tonsiller ectopia was not present. Neurological
      examination of both sisters was normal. They did not undergo surgery as they had
      mild symptoms without neurological deficit and the size of the syrinx was small.
      Familial syringomyelia is a very rare finding and extremely rare at only the
      thoracic level. Genetic and environmental factors seem to be involved in familial
      syringomyelia.

PMID- 18050068
TI  - A rare cause of "foot drop": spinal epidural brucella granuloma.
AB  - Spinal epidural abscess is rare but serious medical condition which may cause
      permanent neurological deficits, or even death, if not treated. Staphylococcus
      aureus is the responsible microorganism in most spinal abscess cases. However,
      rarely other microorganisms like Brucella may be responsible. Brucellosis, a
      zoonotic infection endemic in the Mediterranean Region, Middle East; and South
      and Central America, most frequently involves the reticuloendothelial and
      musculoskeletal systems. Vertebral involvement is rarely seen; and its
      differential diagnosis is rather difficult. Spondylodiscitis and rarely spinal
      abscess or development of a granuloma are the main pathologies. Spinal epidural
      granulomas due to brucellosis may cause neurologic deficits. In this case
      presentation, a spinal epidural brucella granuloma causing foot drop is discussed
      taking other reports into account.

PMID- 18050069
TI  - Intermittent priapism in degenerative lumbar spinal stenosis: case report.
AB  - BACKGROUND: Symptomatic lumbar spinal stenosis produces gradually progressive
      back and leg pain with standing and walking, relieved by sitting or lying. One of
      the uncommon symptoms is involuntary intermittent penile erection due to spinal
      canal stenosis. This symptom is very rare and often forgotten when history is
      taken. METHODS: In this case report, a patient suffering from intermittent
      priapism due to degenerative spinal canal stenosis and spondylolisthesis is
      described. On admission his symptoms were intermittent neurogenic claudication
      and involuntary erection provoked by walking a short distance. RESULTS: Bilateral
      laminectomy and posterior fusion was performed. His symptoms resolved over the
      first postoperative days. CONCLUSION: Cauda equina compression due to LSS may
      rarely cause intermittent priapism. This rare symptom should not be forgotten
      when taking the patient's history and should also be kept in mind during follow
      up.

PMID- 18050070
TI  - Transsellar transsphenoidal rhino-oral encephalocele.
AB  - Transsphenoidal encephaloceles are rare and the transsellar variety is the least
      common. We present a 1-year-old male patient with transsellar transsphenoidal
      encephalocele which herniated into the oral cavity through the congenital split
      palate. The patient was operated on using a combined transcranial and
      transpalatal approach without mortality or permanent morbidity. Clinical
      findings, imaging reviews, surgical repair techniques and postoperative morbidity
      are discussed with the relevant literature. We conclude that repair of a
      transsphenoidal encephalocele should be coordinated between a team of
      neurosurgeons and otorhinolaryngologists. Our surgical outcome supports a
      transcranial approach for the treatment of these difficult lesions, with
      transpalatal dissection and exposure.

PMID- 18050071
TI  - Lumbar radiculopathy due to unilateral facet hypertrophy following lumbar disc
      hernia operation: a case report.
AB  - OBJECTIVE: To present a radiculopathy case due to unilateral facet hypertrophy
      developing three years after a lumbar disc hernia operation. CASE REPORT: A fifty
      two-year-old female patient, who had been operated on for a left L5-S1 herniated
      lumbar disc three years ago, was hospitalized and re-operated with a diagnosis of
      unilateral facet hypertrophy. She had complaints of left leg pain and walking
      restrictions for the last six months. Left Straight Leg Raising test was positive
      at 40 degrees , left ankle dorsiflexion muscle strength was 4/5, left Extensor
      Hallucis Longus muscle strength was 3/5, and left Achilles reflex was hypoactive.
      Lumbar spinal Magnetic Resonance Imaging revealed left L5-S1 facet hypertrophy.
      RESULTS AND CONCLUSIONS: Lumbar radiculopathy due to lumbar facet hypertrophy is
      a well-known neurological condition. Radicular pain develops during the late
      postoperative period following lumbar disc hernia operations that are often
      related to recurrent disc herniation or to formation of post-operative scar
      tissue. In addition, it can be speculated that unilateral facet hypertrophy,
      which may develop after a disc hernia operation, might also be one of the causes
      of radiculopathy.

PMID- 18050072
TI  - Agenesis of the left internal carotid artery associated with anterior
      communicating artery aneurysm: case report.
AB  - We present a rare case of agenesis of the left internal carotid artery in a 43
      year old woman, associated with an aneurysm of the anterior communicating artery
      and presenting with subarachnoid hemorrhage. The left internal carotid artery was
      not visualized on the left carotid angiogram. The left middle cerebral artery was
      perfused from the basilar artery via the dilated posterior communicating artery
      on vertebral angiogram. Absence of the left carotid canal was proven on temporal
      bone computed tomography. Absence of the left internal carotid artery was
      verified at operation. Absence of internal carotid artery is discussed in
      relation to aneurysm formation.

PMID- 18050073
TI  - Ultrasound examination in the surgical treatment for upper extremity peripheral
      nerve injuries: part I.
AB  - AIM: The aim of this clinical study was to evaluate the benefits of
      ultrasonographic imaging in the surgical treatment of upper extremity peripheral
      nerve lesions. MATERIAL AND METHODS: Peripheral nerves in the upper extremity
      were evaluated by using real-time ultrasonographic examination. The capability of
      ultrasonography in terms of determination the type of injury, the position of the
      proximal and distal nerve stumps, the presence or absence of a neuroma and
      perilesional scar tissue were evaluated in cases with peripheral nerve injury.
      RESULTS: Thirty-six cases with upper extremity peripheral nerve injury aged
      between 24 and 60 years were included in this study. Four (11%) had brachial
      plexus injury, 9 (26%) ulnar nerve injury, 6 (16%) radial nerve injury and the
      remaining 17 (47%) cases had median nerve injury. The capability of
      ultrasonographic examination was satisfactory for all evaluation parameters.
      CONCLUSION: Preoperative and intraoperative ultrasonography for upper extremity
      peripheral nerve lesions may be used in the description of the degree of injury,
      determination of complete or incomplete nerve sectioning, the presence of
      hematoma and foreign body, the continuity of the nerve, determination of nerve
      stumps and perilesional scar tissue, and the presence of neuroma.

PMID- 18050074
TI  - Tarsal tunnel syndrome in a patient on long-term peritoneal dialysis: case
      report.
AB  - Tarsal tunnel syndrome (TTS) is defined as the entrapment of the posterior tibial
      nerve in the tarsal tunnel of the ankle. The etiologies of tarsal tunnel syndrome
      are mainly the presence of a ganglion, osseous prominence with tarsal bone
      coalition, trauma, varicose veins, neurinoma, hypertrophy of the flexor
      retinaculum, or systemic disease (rheumatoid arthritis, ankylosing spondylitis).
      However, no specific cause can be identified in some cases. Patients with chronic
      renal failure tend to develop peripheral nerve entrapment and carpal tunnel
      syndrome is the best-known peripheral entrapment neuropathy among them. Contrary
      to carpal tunnel syndrome, tarsal tunnel syndrome is observed less frequently in
      chronic renal failure patients. The common presenting symptoms of TTS are
      paresthesias and/or pain in the plantar side of the foot. Motor symptoms are
      rarely detected. Diagnosis is made primarily by electroneuromyographic studies
      and physical examination. Surgery is the treatment of choice and the outcome is
      generally favourable. In this report, we present a patient with tarsal tunnel
      syndrome complicating peritoneal dialysis.

PMID- 18050075
TI  - Extraaxial chloroma of the cerebellopontine angle: case report.
AB  - A chloroma or granulocytic sarcoma is an extramedullary leukemia. It can be
      encountered at any anatomical location, but until now only three cases have been
      reported in the cerebellopontine angle. We present an 8-year old patient with an
      extraaxial chloroma of the cerebellopontine angle to highlight this very rare and
      malignant pathology in the differential diagnosis of cerebellopontine angle
      tumors. The presented case, being the fourth chloroma in the cerebellopontine
      angle, occurred in the absence of relapse which is very unusual for these
      lesions. Chloroma should be remembered as a very rare and a malignant pathology
      in the differential diagnosis of pediatric cerebellopontine angle tumors.

PMID- 18050076
TI  - Chronic subdural hematoma after endoscopic third ventriculostomy: case report.
AB  - Endoscopic third ventriculostomy (ETV) is an effective and rather safe treatment
      for noncommunicating hydrocephalus secondary to aqueductal stenosis and other
      obstructive pathologies. It has become a popular alternative to ventricular
      shunts for noncommunicating hydrocephalus. Although it is a safe procedure,
      several complications related to this procedure have been reported in the
      literature. We report a rare case of a large chronic subdural hematoma (ChSDH)
      after ETV in a patient with aqueductal stenosis. A 42-year-old female patient
      presented with acute symptoms of obstructive hydrocephalus, headaches and
      blurring of consciousness. A computerized tomogram (CT) of the patient's brain
      revealed marked triventricular supratentorial hydrocephalus and an external
      ventricular drainage (EVD) was performed first. After this procedure, magnetic
      resonance imaging (MRI) demonstrated hydrocephalus secondary to aqueductal
      stenosis. ETV was performed and the EVD removed uneventfully. The patient was
      discharged home after a few days without any complications. She then presented
      with headaches 4 weeks following ETV. A CT demonstrated chronic subdural hematoma
      on the contralateral side. This was treated with burr-hole evacuation.
      Postoperatively, her headaches improved. During the follow-up period, she remains
      symptom-free and has radiographic evidence of a patent ventriculostomy. This case
      confirms chronic subdural hematoma formation is a possible complication following
      endoscopic third ventriculostomy.

PMID- 18050077
TI  - Idiopathic bilateral trigeminal neuralgia treated by bilateral microvascular
      decompression.
AB  - Idiopathic trigeminal neuralgia is the most common type of cranial neuralgia.
      Trigeminal neuralgia is a form of facial pain characterized by proximal
      lancinating pain confined to the somatosensory distribution of the trigeminal
      nerve. Bilateral trigeminal neuralgia is a rare situation with an incidence of 1%
      to 6% in large trigeminal neuralgia series. There is no single or standard method
      for the treatment of bilateral trigeminal neuralgia. Microvascular decompression
      for treatment trigeminal neuralgia is an effective and relatively safe method in
      older patients. We report a rare case of bilateral trigeminal neuralgia treated
      by bilateral microvascular decompression.

PMID- 18050078
TI  - A general review of competition genetic effects with an emphasis on swine
      breeding.
AB  - A review of previous studies is presented on estimates of genetic parameters and
      responses to selection with traditional breeding approaches, on correlations
      between agonistic behavior and growth performance, and on theoretical frameworks
      for selection incorporating interactions among individuals and on practical
      methods for incorporating competition effects in breeding programs.

PMID- 18050079
TI  - Identification of Glomerella cingulata f. sp phaseoli recombinants by RAPD
      markers.
AB  - We examined the capacity of strains of Glomerella cingulata f. sp phaseoli fungus
      (Colletotrichum lindemuthianum sexual stage) to form recombinants, using random
      amplified polymorphic DNA (RAPD). Crosses of all possible combinations between
      strains 40, 42, 20, 21, 22, 23, 24, 25, and 26 were made on Petri dishes using M3
      culture medium. The 42 x 21 cross produced the largest number of perithecia and
      five asci; the respective ascospores were isolated. RAPD analysis was performed
      on the parents and descendants. The 62 polymorphic RAPD bands obtained were used
      to assess the genetic similarity using the method of Sorence and Dice and
      clustering analysis in the form of a dendrogram by the UPGMA method. The RAPD
      markers allowed identification of recombinants from the cross between strains 42
      and 21 of G. cingulata f. sp phaseoli and 40 ascospores presented 63 and 49%
      genetic similarity with parents 2 (strain 42) and 1 (strain 21), respectively.

PMID- 18050080
TI  - Abnormal cytokinesis in microsporogenesis of Brachiaria humidicola (Poaceae:
      Paniceae).
AB  - Microsporogenesis was evaluated in the Brachiaria humidicola collection of the
      Embrapa Beef Cattle Center, represented by 60 accessions. One accession (H121)
      presented an abnormal pattern of cytokinesis that had never been reported in this
      genus. Among 900 meiocytes analyzed in the first division, 10.7% underwent
      precocious and multiple cytokinesis in metaphase I, fractionating the genome and
      the cytoplasm into two or more parts. The expected cytokinesis after telophase I
      did not occur. The abnormal meiocytes from the first division entered the second
      division but the second cytokinesis after telophase II was also abnormal. Among
      the 857 meiocytes analyzed in the second division, 10.9% presented abnormal,
      incomplete or total absence of cytokinesis. Dyads and binucleated microspores
      were recorded among the meiotic products. The use of this accession in the
      Embrapa breeding program is compromised.

PMID- 18050081
TI  - Differentiation of Nijmegen breakage syndrome from Fanconi anemia.
AB  - Nijmegen breakage syndrome (NBS) is a rare auto-somal recessive condition with
      chromosomal instability. Clinical and biological overlap between Fanconi anemia
      and ataxia telangiectasia has been reported. We report two cases of NBS born to
      consanguineous parents. Case one had NBS and Falconi anemia clinical features but
      relatively little chromosome breakage. The second case had mild NBS features,
      while cytogenetic evaluation with mitomycin C induction showed chromosome damage.
      Chromosomal analysis of bone marrow cells revealed tetraploidy, which indicates
      progression towards leukemia. On the basis of clinical and cytogenetic
      evaluation, these two cases were confirmed as NBS. However, detailed molecular
      studies are essential for accurate diagnosis and management of this disease.

PMID- 18050082
TI  - Cytogenetic characterization of Rhamdia quelen (Siluriformes, Heptapteridae) from
      the Bodoquena Plateau, Mato Grosso do Sul, Brazil.
AB  - We made a cytogenetic study of the fish Rhamdia quelen collected from the
      Bodoquena Plateau, an isolated national park region in Mato Grosso do Sul State,
      Brazil. The diploid number was 2n = 58, with 36 metacentric + 16 submetacentric +
      6 subtelocentric chromosomes. We found one to three B chromosomes, which were
      metacentric and submetacentric and of medium size, showing both intra- and
      interindividual variation. The nucleolus organizer region (NOR) was located in
      the terminal region of the short arm of submetacentric pair 20. Staining with
      CMA3 fluorochrome revealed the NOR location, while there was no evidence of
      fluorescent staining with DAPI. C banding revealed heterochromatin mainly in the
      terminal regions of the chromosome arms, including the NOR pair. In addition,
      metacentric pair 2 showed three heterochromatic blocks in the terminal portions
      and in the pericentromeric region. The B chromosomes appeared euchromatic. The CB
      + CMA3 staining combination demonstrated only one chromosome pair with
      fluorescence, probably the NOR-bearing one, while CB + DAPI gave various
      fluorescent signals, including metacentric pair 2, indicating that these
      heterochromatic regions are AT-rich in this population of R. quelen. The R.
      quelen population in this isolated region of Brazil is chromosomally distinct
      from that of other populations that have been studied.

PMID- 18050083
TI  - Vegetative compatibility and parasexual segregation in Colletotrichum
      lindemuthianum, a fungal pathogen of the common bean.
AB  - The heterokaryotic and vegetative diploid phases of Colletotrichum lindemuthianum
      are described using nutritional and biochemical markers. Nitrate non-utilizing
      mutants (nit), derived from R2047, R89, R73, R65, and R23 isolates, were paired
      in all possible combinations to obtain heterokaryons. Although pairings
      R2047/R89, R2047/R73, R65/R73, and R73/R23 showed complete vegetative
      incompatibility, prototrophic heterokaryons were obtained from pairings
      R2047/R65, R2047/R23, R65/R89, R65/R23, R73/R89, R89/R23, R2047/R2047, R65/R65,
      R89/R89, R73/R73, and R23/R23. Heterokaryons gave rise to spontaneous mitotic
      segregants which carried markers corresponding to one or the other of the
      parental strains. Heterokaryons spontaneously produced prototrophic fast-growing
      sectors too, characterized as diploid segregants. Diploids would be expected to
      yield auxotrophic segregants following haploidization in basal medium or in the
      presence of benomyl. Parental haploid segregants were in fact recovered from
      diploid colonies growing in basal medium and basal medium containing the
      haploidizing agent. Although barriers to the formation of heterokaryons in some
      crosses were detected, the results demonstrate the occurrence of parasexuality
      among vegetative compatible mutants of C. lindemuthianum.

PMID- 18050084
TI  - Localization of HSP single-copy genes by inexpensive, permanent non-fluorescent
      in situ hybridization on meiotic chromosomes of the grasshopper Schistocerca
      pallens (Acrididae).
AB  - There have been many studies on Schistocerca gregaria and Locusta migratoria,
      which are important grasshopper pests in many parts of the world. However, the
      main pest grasshopper species in Brazil, S. pallens, Rhammatocerus
      schistocercoides and Stiphra robusta, are very poorly characterized genetically.
      We adapted a permanent in situ hybridization method to extend the genetic
      characterization of S. pallens by mapping the single-copy genes Hsp70, Hsp83,
      Hsp27, and Ubi on meiotic chromosomes. Hsp70 was mapped on the L2 chromosome, in
      which 82% of the signals were observed. Hsp83 was mapped on a medium-sized
      chromosome, on which 81% of the signals were observed, tentatively identified as
      M7. The hybridization signals for the Hsp27 gene were detected on the L1
      chromosome at a frequency of 58%. The main hybridization site of the Ubi probe
      was on the L2 chromosome, with 73% of the signals. All mapped genes also
      presented secondary hybridization signals, always at frequencies below 30%. These
      are the first single-copy genes mapped for S. pallens and also for the Acrididae
      family. Since the Acrididae generally present very similar karyotypes, these data
      are useful as new landmarks for chromosome identification and as a tool for
      phylogenetic studies on the genus Schistocerca and for comparison with other
      insects.

PMID- 18050085
TI  - Cytogenetic characterization of Crenicichla (Pisces, Perciformes, Cichlidae) of
      the Iguacu River.
AB  - Three populations of the genus Crenicichla, namely Crenicichla iguassuensis,
      Crenicichla sp 1 and Crenicichla sp 2, from the Iguacu River, were analyzed
      cytogenetically, and their nucleolus organizer regions, constitutive
      heterochromatin distribution and chromomycin A3 markings were studied. Karyotype
      analyses showed a diploid number of 48 chromosomes, made up of 2 metacentric
      pairs, 2 submetacentric pairs, 7 subtelocentric pairs, and 13 acrocentric pairs
      for the three Crenicichla species and no sexual chromosome differentiation.
      Nucleolus organizer regions showed strong interstitial marking on the first
      chromosome pair, coincident with a constriction presented by Giemsa and positive
      marking by chromomycin. Although constitutive heterochromatin patterns were also
      similar, with pericentromeric markings, small differences in the three species
      could be observed. Crenicichla sp 2 presented some chromosomes with bitelomeric
      markings absent in Crenicichla iguassuensis and Crenicichla sp 1.

PMID- 18050086
TI  - DNA extraction from bristles and quills of Chaetomys subspinosus (Rodentia:
      Erethizontidae) using a novel protocol.
AB  - DNA extraction protocols are as varied as DNA sources. When it comes to
      endangered species, it is especially important to pay attention to all details
      that ensure the completion of the study goals and effectiveness in attaining
      useful data for conservation. Chaetomys subspinosus (Rodentia: Erethizontidae) is
      a secretive arboreal porcupine endemic to certain ecosystems of the Brazilian
      Atlantic Forest. A multidisciplinary study (including genetic data) was performed
      to create a management plan for the conservation of this species. Individuals
      from natural populations of the states of Bahia, Espirito Santo and Sergipe were
      sampled. To obtain a reliable and abundant amount of starting material, non
      destructive methods were tested, extracting DNA from the bristles and quills that
      comprise most of this animal's hide. This method has also been innovative in
      adapting a DNA extraction protocol traditionally used for plants. Digestion using
      proteinase K was followed by protein precipitation with CTAB, a chloroform
      isoamyl alcohol cleaning and DNA precipitation with isopropyl alcohol. This
      protocol supplies good-quality DNA for genetic analysis with molecular markers
      based on PCR.

PMID- 18050087
TI  - Laronidase for treating mucopolysaccharidosis type I.
AB  - Mucopolysaccharidoses are a group of inherited metabolic diseases caused by the
      absence or deficiency of the lysosomal enzymes that are needed for breaking down
      glycosaminoglycans (GAGs). Over time, GAGs collect in cells, blood and connective
      tissues, and increased amounts are excreted in the urine. The result is permanent
      and includes progressive cell damage that affects the individual's appearance,
      physical abilities, organ and system functioning and, in certain cases, mental
      development. Enzyme replacement therapies are currently in use or are being
      tested for at least three different subtypes (I, II and VI). The aim of the
      present study was to evaluate the effectiveness and safety of laronidase for
      treating mucopolysaccharidosis type I. A systematic review of the literature was
      conducted. A computerized electronic search was then conducted using the CENTRAL,
      Pubmed, EMBASE, and LILACS databases, to identify any randomized controlled
      trials. The last date of the search was June 2006. There was no possibility of
      combining the results, because only one study was included. In the pivotal
      placebo-controlled trial conducted over a 26-week period, there was a reduction
      in the urinary excretion of GAGs among treated patients. Regarding adverse
      events, there were no laronidase-related serious adverse events or deaths.
      Laronidase seems to be a promising agent for treating mucopolysaccharidosis type
      I, as shown by the reduction in the urinary excretion of GAGs and the associated
      improvements in vital capacity and in the performance of defined physical tasks.

PMID- 18050088
TI  - Genetic variability of Brazilian Indian landraces of Arachis hypogaea L.
AB  - The Kayabi Indians who inhabit the Xingu Indigenous Park, located in West Central
      Brazil, have grown and managed peanuts for a long time. A great number of
      landraces are being maintained by these tribes and some of this germplasm has
      morphological traits that exceed the variation described in the taxonomic
      literature. Here, we analyzed the genetic variability of these landraces using a
      set of microsatellite markers. The analysis showed that, in general, the
      indigenous samples grouped according to the villages where they were collected.
      The microsatellite markers used in the present study detected high levels of
      genetic variation. Similarity groups, genetically distant from each other, were
      formed, allowing a more efficient use of the existing genetic variability. The
      present study also showed that these materials can extend the genetic variability
      available for peanut-breeding programs. Additionally, the microsatellite markers
      revealed a large dissimilarity among germplasm accessions representing Arachis
      hypogaea varieties so far included in the same subspecies fastigiata
      (aequatoriana + peruviana vs fastigiata + vulgaris), a subject that deserves
      further investigation. Finally, the Xingu Indigenous Park proved to be an
      important center of diversity for peanut.

PMID- 18050089
TI  - Computing numerator relationships between any pair of animals.
AB  - We describe a simple method to compute the numerator relationship between any or
      all pairs of animals in the numerator relationship matrix. The method depends on
      output of the MTDFNRM program from the MTDFREML set of programs. An option of the
      MTDFNRM program creates a file that includes the inbreeding coefficient for each
      animal. The method also makes use of how the inbreeding coefficient is
      traditionally calculated: one-half of the relationship between the animal's
      parents. To obtain the numerator relationship between any pair of animals, the
      original pedigree file is augmented with a dummy animal with an identification
      number (ID) greater than for any animal in the original pedigree file. The ID of
      the pair of animals for which the relationship is wanted is included as parents.
      MTDFNRM is then run with the option to create a file of ordered and original IDs
      for animals and their parents along with the inbreeding coefficients. We then
      multiply the inbreeding coefficient for a dummy animal by two to obtain the
      numerator relationship between the two animals designated as parents.

PMID- 18050090
TI  - Genetic mapping of a new set of microsatellite markers in a reference common bean
      (Phaseolus vulgaris) population BAT93 x Jalo EEP558.
AB  - The present study describes a new set of 61 polymorphic microsatellite markers
      for beans and the construction of a genetic map using the BAT93 x Jalo EEP558
      (BJ) population for the purpose of developing a reference linkage map for common
      bean (Phaseolus vulgaris). The main objectives were to integrate new
      microsatellites on the existing framework map of the BJ population, and to
      develop the first linkage map for the BJ population based exclusively on
      microsatellites. Of the total of 264 microsatellites evaluated for polymorphism,
      42.8% showed polymorphism between the genitors. An integrated map was created
      totaling 199 mapped markers in 13 linkage groups, with an observed length of 1358
      cM and a mean distance between markers of 7.23 cM. For the map constructed
      exclusively with microsatellites, 106 markers were placed in 12 groups with a
      total length of 606.8 cM and average distance of 6.8 cM. Linkage group
      designation and marker order for BM microsatellites generally agreed with
      previous mapping, while the new microsatellites were well distributed across the
      genome, corroborating the utility of the BJ population for a reference map. The
      extensive use of the microsatellites and the availability of a reference map can
      help in the development of other genetic maps for common bean through the
      transfer of information of marker order and linkage, which will allow comparative
      analysis and map integration, especially for future quantitative trait loci and
      association mapping studies.

PMID- 18050091
TI  - Karyotypic studies of Cratylia argentea (Desv.) O. Kuntze and C. mollis Mart. ex
      Benth. (Fabaceae - Papilionoideae).
AB  - Cratylia argentea and C. mollis (Fabaceae-Papilionoideae) are legume shrubs
      native to the Cerrado and Caatinga, respectively. Both species show great
      resistance to drought and high nutritive value, which makes them a valuable
      forage resource in tropical regions. Cytogenetic studies were carried out on
      accessions of C. argentea and C. mollis from Germplasm Banks of Embrapa Gado de
      Leite (Juiz de Fora, MG) and Embrapa Semi-Arido (Petrolina, PE), respectively.
      Root tips were treated with 3 mM 8-hydroxyquinoline and slides were made using
      the air-dry technique. Karyotype description for each accession took into account
      the following features: chromosome number; total length, relative length and arm
      ratio of each chromosome; haploid set length, and degree of asymmetry. Mitotic
      metaphases in both species showed 2n = 22 chromosomes, where this is the first
      report of diploid number for C. mollis. Chromosome length was also quite similar
      for the two species, ranging from 5.08 to 2.50 microm in C. argentea and 5.12 to
      2.51 microm in C. mollis, with haploid sets of equal size, measuring 38.10 and
      37.85 microm, respectively. However, they did not show the same karyotypic
      formula, which was 5 m + 4 sm + 2 st for C. argentea and 7 m + 2 sm + 2 st for C.
      mollis. This indicates the occurrence of rearrangements within chromosomes I and
      VI. Both karyotypes showed a tendency for asymmetry.

PMID- 18050092
TI  - Differential characterization of holocentric chromosomes in triatomines
      (Heteroptera, Triatominae) using different staining techniques and fluorescent in
      situ hybridization.
AB  - A comparative study of holocentric chromosomes in the triatomine species
      Panstrongylus megistus, Rhodnius pallescens and Triatoma infestans was carried
      out in order to characterize heterochromatin, rDNA active sites and nucleolar
      proteins. Cytological preparations of seminiferous tubules were stained by silver
      impregnation, C banding, fluorochromes cma3/da and dapi/da, and fluorescent in
      situ hybridization (FISH) with Drosophila melanogaster 28S rDNA probe. Our
      results showed interesting aspects of the organization of chromatin and
      chromosomes in the meiotic cells of these insects. In R. pallescens, sex
      chromosomes (X, Y) were distinct from autosomes, when submitted to silver
      impregnation, C banding, CMA3 staining, and FISH, confirming that these
      chromosomes bear nucleolar organizer regions (NORs). In P. megistus, two of the
      three sex chromosomes were CMA3/DAPI-; at early meiotic prophase and at
      diakinesis, silver impregnation corresponded with FISH signals, indicating that
      in this species, two chromosomes (probably a sex chromosome and an autosome) bear
      NORs. In T. infestans, silver nitrate and FISH also stained corresponding areas
      on meiotic chromosomes. Our data suggest that in triatomines, in general, the
      number and location of NORs are species-specific. These regions may be considered
      important chromosome markers for comparative studies to improve the understanding
      of evolutionary mechanisms in these hematophagous insects.

PMID- 18050093
TI  - Identification of nutrient-dependent changes in extracellular pH and acid
      phosphatase secretion in Aspergillus nidulans.
AB  - The present study was designed to identify nutrient-dependent changes in
      extracellular pH and acid phosphatase secretion in the biA1 palC4 mutant strain
      of Aspergillus nidulans. The palC4 mutant was selected as lacking alkaline
      phosphatase, but having substantially increased acid phosphatase activity when
      grown on solid minimal medium under phosphate starvation, pH 6.5. Gene palC was
      identified as a putative member of a conserved signaling cascade involved in
      ambient alkaline sensing whose sole function is to promote the proteolytic
      activation of PacC at alkaline pH. We showed that both poor growth and
      conidiation of the palC4 mutant strain on solid medium, alkaline pH, were
      relative to its hypersensitivity to Tris (hydroxymethyl) aminomethane buffer.
      Also, the secretion of acid phosphatase was repressed when both the wild-type and
      palC4 mutant strains were grown in low-phosphate yeast extract liquid medium, pH
      5.0, indicating that the secretion of this enzyme is not necessary to regenerate
      inorganic phosphate from the organic phosphate pool present in yeast extract.

PMID- 18050094
TI  - [Patterns of health resources use and costs in patients with neurological
      disorders in primary care].
AB  - AIM: To determine the pattern of services use and costs of patients requiring
      care for neurological disorders (ND) in primary care in the context of routine
      clinical practice. PATIENTS AND METHODS: We performed a retrospective study of
      all patients older consulting primary care at least once for ND, attended by five
      primary care teams in 2006. A comparative group was formed with the remaining
      outpatients without ND. The main measurements were age, gender, case
      mix/comorbidity, Charlson index (severity) and health resource utilization and
      corresponding outpatient costs (drugs, diagnostic tests and visits). Multiple
      logistic regression analysis and ANCOVA models were applied (Bonferroni adjust),
      p < 0.05. RESULTS: A total of 80,775 patients were assessed, of which 19,423 had
      some type of ND (24%; 95% CI = 23.7-24.3%). Patients consulting for ND had a
      greater number of health problems (6.1 vs. 4.3; p < 0.0001) and higher resource
      consumption, mainly all-type medical visits/patient/year (9.9 vs. 7.2; p <
      0.0001). The mean annual cost per patient was higher for patients with ND (708.25
      vs. 443.10 euros, p < 0.0001), and this difference remained significant after
      adjusting by age, sex and comorbidities, with adjusts cost of 932.87 vs. 712.38
      euros. All components of outpatient management costs were significantly higher in
      the ND group. CONCLUSION: Outpatients seeking care for some type of ND had a high
      number of comorbidities and showed greater annual cost per patient in the primary
      care setting.

PMID- 18050095
TI  - [The psychometric properties of the Spanish version of the stroke-adapted 30-item
      Sickness Impact Profile (SIP30-AI)].
AB  - AIM: To assess the psychometric attributes of the stroke-adapted 30-item version
      of the Sickness Impact Profile, Spanish version (SA-SIP30), in stroke survivors.
      PATIENTS AND METHODS: 79 patients were evaluated (mean age: 68.1 years) by means
      of the modified Rankin Scale (m-RS), Scandinavian Stroke Scale (SSS), Barthel
      Index (BI), and the modified 23-item Beck-Hamilton's Depression Rating Scale
      (HDRS). Health-related quality of life was evaluated using the MOS-Short Form 36
      (SF-36) and the SA-SIP30. RESULTS: SA-SIP30 mean score was 36.8. SA-SIP30 floor
      and ceiling effects were 3.8% and 0%. Regarding SA-SIP30 categories, floor effect
      ranged from 15.2% (social interaction) to 49.4% (alertness behavior), whereas
      ceiling effect ranged from 2.5% (social interaction) to 26.6% (household
      management). A floor effect was observed in seven SA-SIP30 categories. The
      internal consistency of SA-SIP30 (Cronbach's alpha = 0.87), physical (Cronbach's
      alpha = 0.89) and psychosocial (Cronbach's alpha = 0.75) dimensions were
      satisfactory. Standard error of measurement (SEM) values for each SA-SIP30
      category ranged from 15.9 (household management) to 26.3 (ambulation). SEM values
      for overall SA-SIP30, physical and psychosocial dimensions were 8, 10 and 17.3,
      respectively. Corrected item-category correlations ranged from 0.17 (item 28) to
      0.83 (item 23). A significant correlation (Spearman's correlation coefficient; p
      < 0.0001) between SA-SIP30 scores and BI (-0.71), m-RS (0.68), SSS (-0.67), HDRS
      (0.52), SF-36 physical (-0.67) and mental components (-0.51) was found. SA-SIP30
      mean score significantly increased as m-RS increased (discriminative validity;
      Kruskal-Wallis, p < 0.0001). CONCLUSION: The Spanish-version of the SA-SIP30 has
      satisfactory internal consistency, convergent validity and discriminative
      validity in stroke patients.

PMID- 18050096
TI  - [Validity and reliability of the CERAD-Col neuropsychological battery].
AB  - INTRODUCTION: Alzheimer's disease (AD) is an important public health problem due
      to its disabling character and high individual, familial and social costs. The
      CERAD neuropsychological battery has been widely used for evaluation and
      diagnosis of the cognitive deficit associated with AD. This instrument has been
      adapted to the Colombian culture (CERAD-Col) for the Neurosciences Group.
      SUBJECTS AND METHODS: A study was carried out to establish the validity and
      reliability of the CERAD-Col in Colombian, Spanish-speaking individuals aged 50
      years or more. It included 151 controls and 151 AD patients. Controls were
      selected from a convenience sample of 848 adults aged 50 years or more. The
      construct validity was determined in three ways: 1) factorial analysis; 2)
      correlation with the functional scales FAST and GDS (convergent-type validity)
      and, 3) comparison between the two groups. Internal consistency was determined by
      means of Cronbach's alpha coefficient. RESULTS: Three factors -memory, language
      and praxis- explained 88% of the total variance. Moderate but statistically
      significant correlations were found between neuropsychological tests and
      functional scales. Internal consistency and test-retest reproducibility were
      high. The AD group exhibited significantly lower scores (p < 0.05) than the
      control one. CONCLUSION: CERAD-Col is valid and reliable for the diagnosis of AD
      in Colombian Spanish-speaking population aged 50 years or more.

PMID- 18050097
TI  - [The prevalence of clotting disorders in a series of cases of thrombosis of the
      cerebral venous sinuses].
AB  - INTRODUCTION: Cerebral venous sinus thrombosis (CVSTs) constitutes an infrequent
      location of the venous thrombotic disease. It is caused by diverse factors,
      although up to 35% of the CVSTs can remain without aetiologic diagnosis.
      Coagulation disorders have been involved in up to 75% of the CVSTs. AIM. To
      describe the prevalence of coagulation disorders in a consecutive series of
      CVSTs. PATIENTS AND METHODS: We performed a retrospective revision of the
      clinical history of all patients with CVST admitted in our service between
      January, 1st 1995 and December, 31st 2005. The thrombophilic study was carried
      out a posteriori in whatever individual who lacked it. RESULTS: We studied twenty
      one cases (7 men and 14 women), within an age range of 16-69 years old
      (corresponding to an average of 35,4 +/- 14,4 years old). The thrombophilic study
      was carried out in eighteen patients. Five (27,7%) presented some hereditary
      coagulation disorder; in four of them, a hormonal cause coexisted. CONCLUSION:
      Recent advances in the diagnostic procedures for the detection of thrombophilias
      and hereditary prothrombotic mutations have enabled the specialists to be more
      precise in the aetiologic diagnosis of suspected CVST. Even so, the apparent
      cause for a high percentage of patients with CVST has not been found yet.

PMID- 18050099
TI  - [Cap myopathy: a case report].
AB  - AIM: To report a new case of a little-known congenital myopathy. Cap myopathy is
      a rare congenital disease caused by an alteration in the structure of the fibre,
      with disorganised myofibrils at the edges. Since it was first described, only a
      few cases have been reported in the literature. CASE REPORT: We describe the case
      of a 16-year-old patient with a history of neonatal hypotonia and psychomotor
      retardation. At the age of 4 years, the patient presented myopathic facies with
      atrophied pectoral muscles, winged scapula and lumbar hyperlordosis. A myopathic
      pattern was observed in the electromyogram. A muscle biopsy showed a very marked
      predominance of type I fibres, atrophy in part of the population of this type and
      20% of them had cap-shaped subsarcolemmal accumulations, which were intensely
      positive with DPNH and SDH; in the ultrastructural study they correspond to
      disorganised peripheral myofibrils with preservation of the Z band and the
      absence of A bands. These alterations are similar to those described in what is
      known as cap disease or cap myopathy. Today, the patient has mild proximal
      tetraparesis and moderate restrictive respiratory failure.

PMID- 18050098
TI  - [Ziconotide: an innovative alternative for intense chronic neuropathic pain].
AB  - INTRODUCTION: Intense chronic pain is a very important health problem, as it has
      a high prevalence (5-10%), a multifactorial aetiology and its management is very
      often a very complex affair. Treatment of severe cases sometimes requires
      interventional approaches, such as continuous intrathecal infusion of opioids.
      CASE REPORT: We report the case of a 38-year-old female with intense neuropathic
      pain in the lower back and the lower limbs secondary to three operations on the
      L5-S1 lumbar segment. After implementing several different pharmacological
      regimes involving both oral and implanted systems (spinal cord stimulation and
      subarachnoid infusion pump with different pharmacological combinations) with no
      clinical improvement, intrathecal infusion with ziconotide was included in the
      protocol. CONCLUSIONS: Ziconotide is the first specific neuronal blocker that
      acts on the calcium channel by blocking the N-type voltage-dependent calcium
      channels. It is a new non-opioid analgesic with approved indication in the
      treatment of intense chronic pain, in patients who require intrathecal analgesics
      and are refractory to other analgesic treatments. Therefore, we shall have to
      consider this drug as a therapeutic alternative in patients do not experience
      sufficient relief with the pharmacological agents and means currently available
      to treat them.

PMID- 18050100
TI  - [Brain regulation of food intake and expenditure energy: molecular action of
      insulin, leptin and physical exercise].
AB  - INTRODUCTION: Overweight and obesity present significant public health concerns
      because of the link with numerous chronic health conditions. During the last ten
      years, since the discovery of leptin, great advances were obtained in the
      characterization oh the hypothalamic mechanisms involved in the control of food
      intake and thermogenesis. DEVELOPMENT: This review will present some the most
      recent findings in this field. It will be focused on the actions of leptin and
      insulin in the hypothalamus and will explore the hypothesis that hypothalamic
      resistance to the action of these hormones may play a key role in the development
      of obesity. CONCLUSIONS: The physical activity is an important component on long
      term weight control. The exercise markedly increased phosphorylation activity of
      several proteins involved in leptin and insulin signal transduction in the
      hypothalamus. Recently our laboratory showed that physical activity increase in
      sensitivity to leptin- and insulin-induced anorexia after enhances interleukin-6
      production. These findings provide support for the hypothesis that the appetite
      suppressive actions of exercise may be mediated by the hypothalamus.

PMID- 18050101
TI  - [Characterisation and prevalence of the psychological and behavioural symptoms in
      patients with dementia].
AB  - AIM: To assess the prevalence of behavioural and psychological symptoms (BPS's)
      in patients with dementia in Spain and their dementia-specific characteristics.
      PATIENTS AND METHODS: A cross-sectional and retrospective study of 1025 patients
      from 52 specialized dementia care units using the Neuropsychiatric Inventory
      (NPI). Patients with a probable diagnosis of Alzheimer's disease (AD), dementia
      with Lewy bodies (DLB) and Parkinson's disease and dementia (PDD) were selected
      for BPS's characterisation. RESULTS: The global prevalence of BPS's was 66.7%
      (684 patients; 95% CI = 63.8-69.6%). BPS's were under-diagnosed in one third of
      cases. A total of 668 patients with NPI of 4 or superior and a diagnosis of AD (n
      = 380; 56.8%), DLB (n = 156; 23.3%) and PDD (n = 132; 19.7%) had a NPI mean of
      21.1 (SD = 14.7), 25.6 (SD = 13.9) and 21.8 (SD = 14.2), respectively. Apathy,
      depression and anxiety were the most common BPS's. Delusions and hallucinations
      were significantly more prevalent in DLB. Dementia severity was correlated with
      the global NPI value and with all the sub-items, but anxiety and euphoria. The
      presence of agitation, euphoria or lability was associated with a deficient
      therapeutic fulfillment. CONCLUSION: A high prevalence of non-diagnosed BPS's was
      observed in the studied population. This has serious negative consequences for
      the quality of life of patients and their social environment. Therefore we
      propose an active search and subsequent correct treatment of BPS's in all
      patients with dementia.

PMID- 18050102
TI  - [Relationship between essential tremor, Parkinson's disease and dementia with
      Lewy bodies].
AB  - INTRODUCTION: Although essential tremor (ET), Parkinson's disease (PD) and
      dementia with Lewy bodies (DLB) are considered to be distinct illnesses, there is
      a certain overlap between some of their clinical, pathological and genetic
      features. AIM: To conduct a critical examination of the evidence for and against
      the association between these three pathological conditions. DEVELOPMENT: The
      body of evidence supporting the notion of a relation between ET and PD is growing
      all the time; the same can be said of the fact that a postural tremor may appear
      years before the onset of other extrapyramidal symptoms, the involvement of
      common genes in the development of both conditions or the presence of common
      pathological findings. In addition, it has also been suggested that there are
      several aspects linking PD and DLB, and it has even been claimed that that they
      might be part of the clinical spectrum of the same disease. The concept of ET as
      a benign single-symptom disease has changed in recent years and, since it has
      been related to cognitive disorders and Lewy bodies in the central nervous
      system, it is now considered to be a neurodegenerative pathology. CONCLUSIONS.
      ET, PD and DLB could represent different points on the same clinical spectrum.

PMID- 18050103
TI  - [The origins of occupational therapy in Spain].
AB  - INTRODUCTION: Occupational therapy is a young discipline in many aspects, but
      since ancient times an important number of reports have appeared in the health
      sciences literature and in the early days of neurology and psychiatry that can
      shed light on the origins and the fundamental principles that underlie this
      profession today. We have gathered examples that show how the philosophy and the
      clinical practice of the procedures used in occupational therapy stem from the
      process of humanising medical care. AIMS: After analysing the information
      currently available to us on the history of the influence of humanism on the
      development of medicine in Spain, the authors believe they have found enough
      evidence to identify the precursors of occupational therapy at that point in
      history. DEVELOPMENT: Our study examines facts that appear to situate the
      earliest evidence of occupational therapy at the origins of Spanish neurology and
      psychiatry in the 15th century, and which were later to have such a powerful
      influence on the birth of certain aspects of Pinel's moral treatment.
      CONCLUSIONS: If we accept 'moral treatment' as being one of the main forerunners
      of occupational therapy, and if we take into account that the humanitarian way
      patients were dealt with in Spanish neurological and psychiatric institutions and
      hospitals in the 15th century had a notable influence on the principles that
      regulated that 'moral treatment', then it is reasonable to state that the
      earliest evidence of occupational therapy is to be found in the development of
      humanisation within Spanish medical care.

PMID- 18050105
TI  - [Shaken baby syndrome and stroke].

PMID- 18050106
TI  - [Botulinum toxin in disabling stuttering].

PMID- 18050107
TI  - [Preadmission use of statins as treatment for strokes].

PMID- 18050109
TI  - [In memoriam. Cristobal Lamote de Grignon i Nicolau (1913-2006)].

PMID- 18050110
TI  - Dry eye syndrome in diabetic children.
AB  - PURPOSE: To compare the symptoms, signs, and results of objective tests for dry
      eye syndrome (DES) in type 1 diabetes mellitus (T1DM) patients and controls.
      METHODS: A total of 104 children with T1DM and 104 age- and sex-matched controls
      were compared in terms of the symptoms, signs, and results of objective tests for
      DES. Duration of T1DM, presence of diabetic retinopathy, mean hemoglobin A1c
      level, pubertal status, and a history of accompanying autoimmune disease were
      noted in T1DM group. Analysis of variance, multivariate regression analysis,
      Student t, Mann-Whitney U, and chi-square tests were used for statistical
      analysis. RESULTS: A total of 15.4% of diabetic children complained of dry eye
      symptoms, versus 1.9% of the controls (p=0.029). Dry eye signs were detected in
      7.7% of diabetic children, versus 0.96% of controls (p=0.034). Tear break-up time
      (TBUT) and Schirmer test results were significantly lower in T1DM group than
      controls (p=0.018, p=0.024, respectively). A total of 7.7% of diabetic children
      had definite and 0.96% had probable diagnosis of DES, versus none of the controls
      (p=0.03). TBUT and Schirmer test results were significantly lower in patients
      with more than 10 years duration of T1DM (p<0.001 for both). CONCLUSIONS: The
      prevalence of symptoms, signs, and definite diagnosis of DES are higher and basal
      tear secretion and tear film stability are lower in diabetic children than
      controls. Duration of T1DM is the only disease-related variable which is
      associated with basal tear secretion and tear film stability.

PMID- 18050111
TI  - Cyclooxygenase-2 expression in primary and recurrent pterygium.
AB  - PURPOSE: Pterygium is a proliferative, inflammatory, and invasive ocular surface
      disease associated with excessive ultraviolet radiation exposure and has several
      tumor-like characteristics. Cyclooxygenase-2 (COX-2) is an inducible enzyme and
      recently increased expression of the enzyme was found in many cancers and
      premalign lesions. This study was conducted to identify the COX-2 expression in
      pterygium tissues. METHODS: Immunohistochemical staining using a primary antibody
      for COX-2 was performed on 30 specimens with primary pterygium (20 pterygium
      without recurrence and 10 pterygium which recurred during a 12-month follow-up),
      11 specimens with recurrent pterygium, and 8 specimens of conjunctival tumor. As
      a control we used 10 specimens of normal conjunctiva. Extent and intensity of
      cytoplasmic and membranous staining in epithelial cells were evaluated. RESULTS:
      Higher expression of COX-2 was detected in conjunctival tumor (87.5%) specimens
      and recurrent pterygium specimens (72.7%) compared to the both normal conjunctiva
      (30%) and primary pterygium without recurrence (30%). COX-2 expression in primary
      pterygium tissues with recurrence (60%) was not different from primary pterygium
      without recurrence (p=0.114) and recurrent pterygium (p=0.537). However,
      recurrent pterygium tissues were found to express higher COX-2 than primary
      pterygium without recurrence (p=0.022). CONCLUSIONS: COX-2 expression is
      increased in recurrent pterygium tissues and COX-2 expression may be a marker for
      the prediction of recurrence.

PMID- 18050112
TI  - Fixation patterns evaluation by means of MP-1 microperimeter in microstrabismic
      children treated for unilateral amblyopia.
AB  - PURPOSE: The aim of the study was to evaluate the fixation patterns of
      microstrabismic children previously treated for unilateral amblyopia. METHODS:
      Thirty-three children (mean age 7.3+/-1.5 years) were included in the study.
      Visual acuity (VA) was measured using the Early Treatment of Diabetic Retinopathy
      Study charts. Fixationwas assessed by MP-1 microperimeter. Differences in
      position and stability of fixation between the fellow and the microstrabismic
      eyes were calculated by using the percentage of the preferred fixation points
      within central fixation and the percentage of the fixation points within target
      fixation, respectively. For statistical analysis Mann-Whitney test was used. To
      evaluate the influence of age and duration of anti-amblyopic treatment on
      microstrabismic eyes fixation, linear regression analysis was performed. RESULTS:
      In the microstrabismic eyes VA was significantly reduced when compared to the
      fellow eyes (0.1236+/-0.0204 vs 0.0042+/-0.0032 logMAR; p<0.001). Position and
      stability of fixation were significantly better in the fellow eyes (93.21+/-0.65%
      vs 70.91+/-4.80%; p=0.002, and 89.88+/-0.94% vs 71.73+/-2.94%; p<0.001,
      respectively). A significant correlation was found between fixation stability and
      both the duration of anti-amblyopic treatment and pretreatment VA (p=0.024 and
      p=0.009, respectively) and between fixation centrality and pretreatment VA
      (p<0.001). CONCLUSIONS: VA, centrality, and stability of fixation were
      significantly impaired in the microstrabismic eyes. Pretreatment VA was a risk
      factor for fixation impairment. The severity of fixation stability impairment was
      linked to the duration of anti-amblyopic treatment.

PMID- 18050113
TI  - In vivo confocal microscopy of corneal grafts shortly after penetrating
      keratoplasty.
AB  - PURPOSE: To describe the microstructural status of corneal grafts shortly after
      penetrating keratoplasty (PK) and to evaluate the efficacy and safety of confocal
      microscopy in examining corneal grafts at that time. METHODS: A confocal
      microscope with a 40 x front lens was used to examine corneal grafts in 32
      patients (32 eyes) 4 days after PK. Images were analyzed, and endothelial cell
      density counts were compared with presurgical, eye bank values determined by
      specular microscopy. RESULTS: Microstructural alterations of the graft included
      epithelial and stromal edema, epithelial degeneration in both superficial and
      basal cell layers, dark stromal striae, activated keratocytes, and needle-like
      structures in the stroma. Descemet membrane folds were visible in 31 of 32
      grafts; in 1 graft, the dense stromal edema did not allow imaging of posterior
      layers. Stromal nerve fibers were imaged in 28 grafts (88%). Endothelial cell
      density ranged from 1666 to 2548 cells/mm2 (mean+/-SD, 2125+/-283 cells/mm2);
      perioperative endothelial cell density loss varied from 0% to 29% (mean, 12%). No
      adverse reactions or signs of worsening of clinical condition were observed after
      the examination. CONCLUSIONS: White light scanning slit confocal microscopy
      permits imaging of a graft's microstructure (including epithelium and stromal
      layers), as well as calculation of endothelium cell density, as soon as 4 days
      after PK. The most frequently observed morphologic alterations of corneal grafts
      shortly after PK include epithelial and stromal edema, epithelial degeneration,
      stromal striae, and Descemet membrane folds. Stromal nerves can still be seen in
      the graft 4 days after PK.

PMID- 18050114
TI  - Air-guided manual deep anterior lamellar keratoplasty: long-term results and
      confocal microscopic findings.
AB  - PURPOSE: To evaluate the long-term results of air-guided manual deep anterior
      lamellar keratoplasty (DALK) and to perform confocal microscopy on postoperative
      DALK corneas. METHODS: Seven postoperative consecutive DALK corneas were
      evaluated 1 year after suture removal. All patients underwent a complete
      ophthalmologic examination evaluating visual acuity, astigmatism, corneal
      thickness, and endothelial cell count. Confocal microscopy was performed to
      examine the corneas of the seven eyes and to obtain the measured interface depth.
      RESULTS: Eighteen months after surgery, the mean postoperative uncorrected visual
      acuity was 20/38 and the mean best-corrected visual acuity was 20/23.
      Postoperative mean value of residual recipient stroma thickness was 65.57 microm
      +/- 28.74. CONCLUSIONS: Maximum depth DALK can lead to significant advantages for
      quality of vision when compared to other types of anterior lamellar keratoplasty.
      Still, it remains a challenging procedure. These results show that a deep
      dissection without baring Descemet membrane makes good visual results possible,
      preventing corneal perforation and conversion to penetrating graft.

PMID- 18050115
TI  - Behaviour of the phakic iris-claw intraocular lens (Artisan /Verisyse) during
      accommodation: an optical coherence biometry study.
AB  - PURPOSE: To evaluate variations in the position of the phakic iris claw lens
      (Artisan, Verisyse) and the natural crystalline lens during the accommodation
      process. METHODS: We measured changes in position of the iris claw lens and the
      crystalline lens during the accommodation using optical coherence biometry (AC
      Master/Carl Zeiss Meditec, Germany) in 17 patients (28 eyes) with a phakic iris
      claw lens implanted for high myopia and/or myopic astigmatism. Accommodative
      effort was obtained using an internal optical target within the measuring device.
      RESULTS: There was a forward shift of the phakic iris claw lens with a mean of 70
      microm (8-178 microm) of the optical path length (OPL). At the same time the
      anterior pole of the natural lens showed a forward mean movement of 85 microm (4-
      260 microm). CONCLUSIONS: An anterior displacement of the iris-claw phakic lens
      was shown in a series of eyes during the accommodation process. As this
      displacement goes along with the forward displacement of the anterior pole of the
      crystalline lens, the preoperative measurement of the latter might provide some
      additional information about the position of the iris claw lens in the
      accommodative state after implantation.

PMID- 18050116
TI  - Clinical features, complications, and incidence of intraoperative floppy iris
      syndrome in patients taking tamsulosin.
AB  - PURPOSE: To evaluate the intraoperative findings, complication rates, effect of
      intracameral adrenaline, and incidence of intraoperative floppy iris syndrome
      (IFIS) in patients using tamsulosin. METHODS: In this prospective nonrandomized
      observational study, 858 eyes of 774 patients who had phacoemulsification between
      August 2005 and November 2006 were evaluated. Duration and preoperatively
      discontinuing time of tamsulosin intake were questioned. Preoperative pupil size,
      intraoperative iris behavior, progressive miosis, adrenalin usage, and
      complications were recorded. RESULTS: The incidence of IFIS was 1.6% and IFIS was
      seen in 14 of the 18 eyes of patients using tamsulosin (77.8%). One eye had
      floppy iris only, 2 eyes had floppy iris and intraoperative miosis, 3 eyes had
      floppy iris and iris prolapse, and 8 eyes had all three signs of IFIS. IFIS was
      seen in 7 of the 10 eyes where intracameral adrenaline was used, and in 7 of the
      8 eyes without adrenaline (p=0.588). Intraoperative miosis was seen only in 3 of
      the 10 eyes with adrenaline and in 7 of the 8 eyes without adrenaline (p=0.025).
      Posterior capsule rupture occurred in 1 of the eyes with IFIS and in 5 eyes focal
      iris stromal atrophy caused by prolapse was seen. CONCLUSIONS: IFIS occurred in
      1.6% of cases having phacoemulsification. Intracameral adrenaline usage did not
      change the IFIS occurrence rate, but it seemed to be effective in preventing
      intraoperative miosis. There are still many questions about IFIS, and there is
      need for future studies strengthening the understanding of IFIS.

PMID- 18050117
TI  - Prevalence of diplopia related to cataract surgery among cases of diplopia.
AB  - PURPOSE: To evaluate the prevalence of diplopia in Greece after cataract surgery
      among diplopia cases. METHODS: The authors retrospectively reviewed the medical
      records of 571 patients with diplopia over an 8-year period in order to evaluate
      the prevalence of diplopia related to cataract surgery. The surgical and
      anesthetic records were also reviewed. All patients had full orthoptic assessment
      including prisms with cover test in all gaze positions. The chi-square and cross
      tabulation statistical tests were used for statistical analysis. RESULTS: Thirty
      nine cases (6.8%) were having persistent diplopia related to cataract surgery.
      Type of anesthesia was peribulbar. Hyaluronidase was not used. Thirteen patients
      were men and 26 were women. Left eyes were involved in 22 cases (56.4%), right in
      17 cases (43.6%). Mean age was 72.5 years. Patients were divided into four
      groups. Group 1 consisted of 29 patients related to surgical trauma due to
      anesthesia. Group 2 consisted of 7 patients related to pre-existing disorders.
      Group 3 consisted of 2 patients related to aniseikonia or anisometropia. Group 4
      with 1 patient related to macular pathology. Vertical diplopia was mostly noted
      (28 cases). Twenty-nine patients were corrected with prisms, 9 needed strabismus
      surgery, and 1 needed both surgery and prisms. CONCLUSIONS: Cataract surgery is
      not a common cause of persistent diplopia. However, this report highlights that
      prevalence of diplopia related to cataract is high among cases of diplopia in
      general, with diplopia being mostly vertical (p=0.001), affecting females
      (p=0.006), and being more common in left eyes, although results did not reach
      statistical significance (p=0.133).

PMID- 18050118
TI  - Pre- and postoperative C-reactive protein levels in patients with cataract and
      age-related macular degeneration.
AB  - PURPOSE: To assess whether patients with early or intermediate forms of age
      related macular degeneration (AMD) benefit from cataract surgery in terms of
      visual acuity and contrast sensitivity, and to determine the levels of high
      sensitivity C-reactive protein (hsCRP) as a systemic marker of inflammation
      before and after cataract surgery in patients with AMD. METHODS: Three groups of
      patients (n=132) were studied at baseline and 8-12 weeks later: 1) a study group
      of patients with AMD who underwent cataract surgery (n=47), 2) a control group of
      patients without ocular comorbidities who underwent cataract surgery (n=36), and
      3) a second control group with AMD and no surgery (n=49). Visual acuity (VA) was
      obtained by letter charts and expressed as decimal notations +/- SD. Contrast
      sensitivity was measured employing a Ginsburg Box, VSCR-CST-6500. The hsCRP was
      measured by means of particle enhanced immunonephelometry on a BN Systems.
      RESULTS: Postoperatively in both groups of the operated patients an improvement
      of VA (0.23+/-0.17 vs 0.64+/-0.25 and 0.23+/-0.18 vs 0.83+/-0.17, respectively,
      p<0.0001) and contrast sensitivity (at different spatial frequencies, from 1.5 to
      18 cycles/degree, p<0.05) was determined. At baseline, the hsCRP level in Group 1
      patients was higher than the level in controls (2.67+/-2.36 vs 1.67+/-1.36,
      p<0.01, or 1.12+/-0.99 mg/L, p<0.0001, respectively). After 8-12 weeks, the hsCRB
      level only in Group 1 significantly increased (2.67+/-2.36 vs 3.74+/-3.54 mg/L,
      p<0.05), whereas in the controls it did not change. CONCLUSIONS: Patients with
      AMD benefit from cataract surgery, both in terms of VA and contrast sensitivity.
      The level of hsCRP is significantly higher in patients with AMD and moderate
      cataract than in patients with one of these eye disorders. The hsCRP only
      increases after cataract surgery in patients with AMD.

PMID- 18050119
TI  - Glaucoma drainage implants in the treatment of refractory glaucoma in pediatric
      patients.
AB  - PURPOSE: The aim of this study is to report the clinical course, effectiveness,
      and safety of glaucoma drainage implants (Molteno and Baerveldt devices) in
      primary and secondary childhood glaucomas refractory to conventional surgical
      treatments and medical therapy. METHODS: This retrospective study included 76
      children (76 eyes) younger than 18 years who underwent glaucoma drainage device
      (GDD) implantation in our clinic between 1990 and 2004. The mean age at time of
      surgery was 6.9+/-5.3 years (range: 4 months to 17.5 years). Intraocular pressure
      (IOP), visual acuity, corneal diameter, axial length, intraoperative and
      postoperative complications, and number of glaucoma medications were evaluated.
      Criteria for success were defined as IOP between 7 and 22 mmHg with or without
      glaucoma medications, no further glaucoma surgery, the absence of visually
      threatening complications, and no loss of light perception. Results were compared
      for children with primary and secondary glaucomas. The mean follow-up was 7.1+/
      6.5 years (range: 1.6 to 15.2 years). RESULTS: Mean preoperative and
      postoperative IOP was 33.6+/-11.4 mmHg and 17.1+/-6.5 mmHg (p<0.001),
      respectively. Kaplan-Meier survival analysis showed cumulative probability of
      success: 93% at 6 months, 91% at 1 year, 82% at 2 years, 76% at 3 years, 71% at 4
      years, 67% at 5 years, and 65% at 6 years. There was no difference between
      patients with primary (n=31 eyes) and secondary glaucoma (n=45 eyes) in terms of
      cumulative success (p=0.186), final IOP, number of medications, or length of
      follow-up. On average, the GDI surgery was successful for a mean period of 6.7
      years. Fourteen eyes of 76 (18.4%) failed: 10 eyes with uncontrolled IOP, 2 eyes
      with retinal detachment, and 2 eyes with no light perception. Statistical
      regression model did not show influence of gender and previous surgery. Lower age
      at the time of surgery was found to be associated with higher probability of
      treatment failure. CONCLUSIONS: Molteno and Baerveldt glaucoma drainage implants
      surgery seems to be safe and effective treatment for primary and secondary
      pediatric glaucoma refractory to the initial surgical procedure and medical
      therapy.

PMID- 18050120
TI  - Increased vascular endothelial growth factor levels in aqueous humor and serum of
      patients with quiescent uveitis.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are
      angiogenic mediators that share a significant proinflammatory activity. Both
      substances have been suggested to play a key role in uveitis pathogenesis. The
      authors analyzed VEGF and IL-8 levels in the aqueous humor and serum of patients
      with different types of uveitis during a quiet phase of the disease. METHODS:
      Thirteen patients with intermediate uveitis, uveitis associated with ankylosing
      spondylitis, Vogt-Koyanagi-Harada disease, Fuchs uveitis syndrome, idiopathic
      chronic anterior uveitis, or Behcet disease, as well as 10 normal matched
      subjects, were included in the study. VEGF and IL-8 concentrations were measured
      in aqueous humor and serum by enzyme-linked immunosorbent assay. RESULTS: VEGF
      levels were significantly higher in both the aqueous humor and serum of patients
      with uveitis as compared with controls. IL-8 concentrations in aqueous humor were
      significantly higher in patients with uveitis with extraocular manifestations
      than in those with eye-limited disease. CONCLUSIONS: These findings suggest that
      VEGF plays a role in uveitis pathogenesis even during inactive disease and that
      IL-8 levels are significantly influenced by the presence of uveitis-associated
      extraocular changes.

PMID- 18050121
TI  - The effect of complement factor H Y402H polymorphism on the outcome of
      photodynamic therapy in age-related macular degeneration.
AB  - PURPOSE: Photodynamic therapy (PDT) has been widely used in the treatment of age
      related macular degeneration (AMD). The complement cascade has an important role
      in the tissue reactions occurring after PDT. The Y402H polymorphism of the
      complement factor H (CFH) gene has been identified as a risk factor for AMD.
      Since CFH is central in the regulation of the complement system the authors
      wanted to analyze whether the CFH Y402H polymorphism modifies the PDT outcome in
      AMD. METHODS: A total of 88 patients having been treated with PDT and without
      further scheduled PDT sessions were analyzed. Depending on the situation at their
      final PDT session the patients were classified retrospectively as PDT-responders
      or PDT-nonresponders. All patients were genotyped for the CFH Y402H polymorphism.
      RESULTS: The proportion of PDT-responders was 18/26 (69.2%) in patients
      homozygous for the CFH Y402H risk allele, 34/50 (68.0%) in heterozygous, and 7/12
      (58.3%) in patients with the normal genotype (p=0.520). The median number of PDT
      treatments of the PDT-responders was three for all the genotypes. CONCLUSIONS:
      The dysfunction of the CFH related to the risk of AMD and caused by the Y402H
      polymorphism does not modify the outcome of PDT. Genotyping for CFH Y402H cannot
      be used to select patients for this treatment.

PMID- 18050122
TI  - Assessment of the contribution of insulin-like growth factor I receptor 3174 G-
      >A polymorphism to the progression of advanced retinopathy of prematurity.
AB  - PURPOSE: Retinopathy of prematurity (ROP) is a leading cause of blindness in
      children with short gestational age and low birthweight. The condition can cause
      abnormal vessel development that can lead to retinal detachment and blindness. It
      has been recently reported that a low level of insulin-like growth factor I (IGF
      I) is associated with ROP. However, the most prevalent polymorphism of IGF-I
      receptor (IGF-IR 3174 G-->A) that was reported to be producing low level of IGF-I
      was not found to be associated with ROP in a certain population. In order to
      reproduce this data in a different cohort and to learn more about the
      contribution of IGF-IR polymorphism to ROP, the authors hypothesized that it is
      possible that such a polymorphism would occur more frequently in a different
      cohort of infants with advanced ROP than those children with mild or no disease.
      METHODS: For genetic analysis, eligible patients were selected consecutively by
      experienced pediatric ophthalmologists and leukocyte DNA from affected (n=52) and
      normal patients (n=33) were amplified by polymerase chain reaction. The amplified
      products were subjected to restriction enzyme digestion with 10 units of MnlI
      enzyme. The digested products were analyzed by polyacrylamide gel electrophoresis
      followed by ethidium bromide staining to visualize the restriction fragment
      length polymorphism. RESULTS: The analysis suggests that there is no
      statistically significant difference in allelic frequency of the most prevalent
      IGF-IR gene polymorphism between normal subjects and patients with ROP in this
      cohort. The G-->A polymorphism did not occur more frequently in patients with
      ROP. CONCLUSIONS: The results do not support the association of the most
      prevalent IGF-IR gene polymorphism and the risk of advanced ROP in a different
      cohort, confirming the earlier report.

PMID- 18050123
TI  - Extended silicone oil tamponade in primary vitrectomy for complex retinal
      detachment in proliferative diabetic retinopathy: a long-term follow-up study.
AB  - PURPOSE: To investigate long-term anatomic and functional results of extended
      silicone oil (SO) tamponade in primary vitrectomy for patients with proliferative
      diabetic retinopathy (PDR) and complex retinal detachment (RD). METHODS: From
      January 1999 to June 2005, clinical records of consecutive patients with PDR who
      underwent primary vitrectomy with extended SO tamponade for complex RD were
      retrospectively reviewed. Main outcome measures included anatomic outcome,
      functional outcome, and postoperative complications. Statistical analyses were
      used to determine factors affecting anatomic and functional outcomes and to
      evaluate the potential adverse effects on vision from long-term oil tamponade.
      RESULTS: Fifty-four eyes of 45 patients (18 male and 27 female) were included in
      this series. All patients underwent follow-up >or= 12 months (28.2+/-15.1 months;
      range: 12 to 69 months). Anatomic success was achieved in 85.2% at the third
      month postoperatively and 83.3% at last followup. Breaks with adjacent unreleased
      traction was identified as the only variable associated with final anatomic
      success (OR=0.173, p=0.024). Best-corrected visual acuity (BCVA) improved or
      remained unchanged in 89% at the third month postoperatively and in 78% at last
      follow-up. Ambulatory vision was achieved in 41% at the third month postoperative
      and 44% at last follow-up. Preoperative BCVA was identified as the only variable
      statistically associated with final BCVA (p<0.001) (multivariate analysis). The
      change of BCVA from the third month to last follow-up has no correlation with
      follow-up duration in the 45 eyes with final anatomic success (Pearson
      correlation coefficient = -0.022, p=0.888). Postoperative complications included
      peri-silicone oil proliferation in 4 eyes, neovascular glaucoma in 4 eyes, oil
      migration into anterior chamber in 9 eyes, and pupillary-block induced IOP
      elevation in 5 eyes. CONCLUSIONS: Prolonged SO tamponade may provide anatomic
      success and functional stability after primary diabetic vitrectomy. Significant
      complications compromising visual prognosis were uncommon with prolonged SO
      tamponade.

PMID- 18050124
TI  - Ocular manifestations of chronic graft-versus-host disease in patients treated
      with extracorporeal photochemotherapy.
AB  - PURPOSE: Eye involvement has long been appreciated in patients with chronic graft
      versus host disease (cGVHD). In particular, ocular complications are frequent and
      can be potentially severe in patients with steroid-refractory cGVHD, and
      therefore necessitate close monitoring. This prospective study was designed to
      describe eye manifestations of cGVHD in a large series of patients monitoring
      them before and after 1 year of extracorporeal photochemotherapy (ECP). ECP is a
      relatively new therapeutic approach based on the biological effects of psoralen 8
      methoxypsoralen (8-MOP) and ultraviolet A light (UVA) on mononuclear cells
      collected by apheresis, and reinfused into the patient. METHODS: Only patients
      with steroid-refractory cGVHD under treatment with ECP, who developed cGVHD
      related eye symptoms, were selected for the study. Ophthalmologic examination was
      repeated every 3 months. Only patients with complete recovery of the ocular
      manifestations and symptoms were considered responsive. RESULTS: In our study we
      observed eye alterations in 24 out of 140 patients (17%) with cGVHD. After 12
      months of ECP, 10 out of 21 patients (48%) completely responded to the therapy.
      In all these cases the contribution of ECP was also essential in all the other
      organs subject to cGVHD. CONCLUSIONS: Further studies are necessary to clarify
      the role of ECP in patients with cGVHD, especially in associated eye
      manifestations. Although our experience is limited, it suggests that ECP could be
      a safe and effective therapy for steroid-refractory eye manifestations of cGVHD.

PMID- 18050125
TI  - Squamous cell carcinoma presenting as an orbital cyst with radiologic evidence of
      perineural invasion.
AB  - PURPOSE: To report clinical and radiologic findings of cystic squamous cell
      carcinoma (SCC) of the orbit with evidence of perineural involvement. METHODS:
      Analysis of clinical findings and radiology with a literature review. RESULTS: A
      66-year-old man with SCC of the forehead 8 years prior presented with
      paraesthesias, diplopia, and proptosis. Magnetic resonance imaging showed a well
      defined, cystic mass of the orbit with a single, linear structure running through
      its center. Lateral orbitotomy revealed a cyst adherent to adjacent periorbita
      containing viscous, clear, yellow substance and a nerve coursing through the
      center. Histopathology confirmed poorly differentiated spindle cell carcinoma
      with positive staining for cytokeratin markers, consistent with SCC. CONCLUSIONS:
      Orbital cysts associated with altered sensation are suggestive of SCC with
      perineural spread, requiring prompt investigation and treatment to minimize
      morbidity and mortality. The involved nerve may be seen as a single, linear
      structure within the mass on imaging.

PMID- 18050126
TI  - Unilateral vernal keratoconjunctivitis: a case report.
AB  - PURPOSE: A rare case of unilateral vernal keratoconjunctivitis is presented.
      METHODS: A 5-year-old boy had itching, foreign body sensation, redness, and
      ptosis in his left eye. Impression cytology specimens were taken from both upper
      eyelid tarsal conjunctiva. RESULTS: On slit-lamp biomicroscopy, unilateral
      cobblestone papillae and a shield ulcer were found in the left eye. On impression
      cytology examination, there was a significant increase in inflammation, presence
      of a honeycomb pattern, plasma cells, and mucus strands in the upper tarsal
      conjunctiva of the specimens. CONCLUSIONS: Giant papillary conjunctivitis must be
      considered in differential diagnosis of unilateral vernal conjunctivitis.
      Impression cytology method may be combined with the clinical findings in vernal
      keratoconjunctivitis diagnosis.

PMID- 18050127
TI  - Peribulbar tramadol, clonidine, and ropivacaine in blind and seeing painful eyes.
AB  - PURPOSE: To report on the treatment of painful eyes by peribulbar injection of
      tramadol, clonidine, and ropivacaine. METHODS: The authors treated a 72-year-old
      woman with chronic prephthisical pain in the left eye secondary to graft
      rejection after penetrating keratoplasty and an 81-year-old woman with severe
      ocular pain in her left eye for neovascular glaucoma secondary to an ischemic
      central vein occlusion. They were treated with a medial canthus injection of
      tramadol (100 mg/2 mL ampules), clonidine (0.15 mg/1 mL ampules), and 1%
      ropivacaine. RESULTS: Both injections were very well tolerated and neither
      transient nor lasting complications were reported. Complete pain relief was
      obtained in both patients within 1 day and was maintained throughout the follow
      up (11 months and 7 months). CONCLUSIONS: Peribulbar tramadol, clonidine, and
      ropivacaine injection may represent a safe and effective treatment modality in
      the management of chronic ocular pain.

PMID- 18050129
TI  - Intravitreal bevacizumab for adult-onset vitelliform dystrophy: a case report.
AB  - PURPOSE: Adult-onset foveomacular vitelliform dystrophy (AFVD) is often
      misdiagnosed as occult choroidal neovascularization (CNV) secondary to age
      related macular degeneration (AMD). The authors report the anatomic and
      functional outcome of intravitreal bevacizumab in a case of AFVD associated with
      a suspected occult CNV. METHODS: Prospective, interventional, single case report.
      One female patient with decreased visual acuity (VA) and metamorphopsia secondary
      to AFVD received one single intravitreal injection of bevacizumab 1.25 mg.
      RESULTS: The patient reported unchanged VA and decreased metamorphopsia 6 weeks
      after the injection. Fluorescein angiography (FA) and optical coherence
      tomography (OCT) showed progressive decrease of subretinal fluid until complete
      disappearance. VA, OCT, and FA remained unchanged during 10 months follow-up.
      CONCLUSIONS: Intravitreal bevacizumab showed a morphologic improvement and stable
      VA in a patient with AFVD. Further case series are required to confirm this
      observation.

PMID- 18050128
TI  - Retinal angiomatous proliferation reactivation 6 months after high-dose
      intravitreal acetonide triamcinolone and photodynamic therapy.
AB  - PURPOSE: To describe the incidence of retinal angiomatous proliferation (RAP)
      reactivation after combined treatment with a high-dose intravitreal triamcinolone
      acetonide (IVTA) and photodynamic therapy (PDT) at 1-year follow-up. METHODS: All
      patients had undergone a full ophthalmic examination. High-dose IVTA (20 mg) was
      injected via pars plana. Four to 7 days later, PDT was delivered. RESULTS:
      Fourteen eyes of 13 patients were included. Eight lesions (57%) reopened and
      needed retreatment with combined therapy at 6 months follow-up. At 1-year follow
      up, the lesion was obliterated in nine cases (64.2%) and best-corrected visual
      acuity improved from 0.87 logMar (range, 0.7-1) to 0.79 logMar (range, 0.5-1).
      CONCLUSIONS: Combined therapy using high-dose IVTA and PDT is beneficial in
      stabilizing RAP. However, a high incidence of RAP reactivation has been observed
      at 6 months, even with a high-dose IVTA injection.

PMID- 18050130
TI  - Systemic bevacizumab for retinal angiomatous proliferation associated with
      retinal pigment epithelial detachment.
AB  - PURPOSE: To report the off-label use of systemic bevacizumab in a patient with
      stage 3 retinal angiomatous proliferation (RAP) associated with a vascularized
      pigmented epithelium detachment (PED). METHODS: Interventional case report.
      RESULTS: The patient was treated with systemic bevacizumab after obtaining fully
      informed consent. At 3 months post-treatment, the authors observed an improvement
      of one line (seven letters) in visual acuity and total regression of the PED on
      ocular coherence tomography. No adverse effects were observed. CONCLUSIONS:
      Systemic bevacizumab therapy appears to be safe and effective in the treatment of
      RAP associated with PED during this short follow-up period of 3 months. The
      authors recommend a large trial with long-term follow-up to confirm the promising
      results and evaluate the occurrence of adverse effects associated with systemic
      bevacizumab.

PMID- 18050132
TI  - Intravitreal ranibizumab in a patient with choroidal neovascularization secondary
      to multiple evanescent white dot syndrome.
AB  - PURPOSE: To report the effect of a single intravitreal injection of ranibizumab
      in a patient with choroidal neovascularization (CNV) secondary to multiple
      evanescent white dot syndrome (MEWDS). METHODS: A 65-year-old woman with visual
      acuity (VA) 20/40, mild vitreous inflammation, optic disc edema, and white deep
      retinal round lesions in the right eye underwent fluorescein angiography,
      indocyanine green angiography, and optical coherence tomography. The diagnosis of
      MEWDS with peripapillary CNV was made and a single injection of ranibizumab (0.5
      mg) was administered. RESULTS: At the 6-month follow-up visit, the VA in the
      right eye was 20/20, the CNV completely regressed, and the MEWDS findings
      disappeared. CONCLUSIONS: Intravitreal ranibizumab appears to be a safe and
      effective treatment option in cases of CNV secondary to MEWDS, resulting in fast
      resolution of the macular edema and regression of the CNV. On the other hand, it
      is unclear whether the administration of ranibizumab contributed to a prompt
      regression of MEWDS.

PMID- 18050131
TI  - Retinal pigment epithelial tears after intravitreal bevacizumab injection for
      predominantly classic choroidal neovascularization.
AB  - PURPOSE: To detect retinal pigment epithelium (RPE) tears in predominantly
      classic choroidal neovascularization (CNV) secondary to age-related macular
      degeneration (AMD) treated with intravitreal bevacizumab injections. METHODS:
      Forty consecutive patients with predominantly classic CNV secondary to AMD were
      treated with 1.25 mg of intravitreal bevacizumab. Patients were evaluated with
      visual acuity (VA) measured with Early Treatment Diabetic Retinopathy Study
      charts, optical coherence tomography, and fluorescein angiography. RESULTS: Three
      patients developed a RPE tear after the first injection. The first patient had
      been treated with verteporfin therapy and VA remained unchanged. In the other two
      cases the CNV was naive and VA improved since the foveal center was not involved
      by the tear and macular edema was reduced. CONCLUSIONS: RPE tears can occur
      following intravitreal bevacizumab injections in patients with predominantly
      classic CNV although VA is not always affected.

PMID- 18050133
TI  - Phenotypic intrafamilial variability associated with S212G mutation in the
      RDS/peripherin gene.
AB  - PURPOSE: To describe an Italian family in which two separate phenotypes
      (retinitis pigmentosa and adult onset vitelliform macular dystrophy) are
      associated with an identical mutation (S212G) in the peripherin/RDS gene. This
      mutation has already been reported in patients with retinitis pigmentosa, but it
      has never been previously detected in association with adult onset vitelliform
      macular dystrophy. METHODS: A 38-year-old woman complained of bilateral mild
      metamorphopsias and on ophthalmologic examination she showed the clinical
      phenotype of adult onset vitelliform macular dystrophy. Her 62-year-old mother
      was clinically diagnosed with a retinitis pigmentosa, with a severe clinical
      course. RESULTS: In both patients, molecular genetic analysis revealed a 874A-->G
      transition in the exon 2 of the RDS gene leading to the amino acid change of
      S212G. CONCLUSIONS: Peripherin/RDS S212G mutation may have damaging effects on
      the formation and stability of the photoreceptors' disk structure and may be
      associated with different clinical phenotypes, even in the same family.
      Intrafamilial phenotypic variability has been reported for other RDS mutations;
      this supports the possible influence of modifier genes or environmental factors
      in the clinical expression of RDS gene variants. Moreover, it suggests that in
      patients with retinal degeneration and peripherin/RDS mutation, caution should be
      taken both in using molecular genetic results to predict the clinical course of
      the disease and in offering genetic counseling.

PMID- 18050134
TI  - Protein S deficiency and retinal arteriolar occlusion in pregnancy.
AB  - PURPOSE: To report two cases of retinal arteriolar occlusion in pregnant women
      with transient protein S (PS) deficiency. METHODS: Observational case reports.
      RESULTS: Two pregnant women in their 30s presented with a paracentral scotoma in
      their right and left eye, respectively. In both cases the only risk factor for
      vascular occlusion was pregnancy. Systemic diseases were excluded. Free and
      functional PS activity was physiologically reduced in both patients. In Case 1,
      free PS was 47% and functional PS was 22%. In Case 2, free PS was 43% and
      functional PS was 25%. These levels of PS seem to be lower than those published
      for normal pregnancy. CONCLUSIONS: There might be a special relationship between
      PS deficiency and the development of arterial occlusion in pregnant women. A
      direct effect may be possible. Although the prevalence and incidence of
      vasoocclusive disease in these patients are low, PS deficiency should be
      considered as another risk factor. Further studies are necessary to evaluate
      changes in PS and to assess its relationship with thromboembolic events during
      pregnancy.

PMID- 18050135
TI  - Correlates of vitamin A deficiency among Indian rural preschool-age children.
AB  - PURPOSE: In India, 52,000 children go blind every year on account of vitamin A
      deficiency. The purpose of the study was to determine the correlates of vitamin A
      deficiency among 4,205 preschool-age children. METHODS: Case-control study in
      Bihta Primary Health Center area, Bihar, India. Main outcome measures were
      dietary habits, maternal literacy, and birth order. RESULTS: Vitamin A deficiency
      was found to be significantly higher (p<0.01) in children on a vegetarian diet
      (7.14%) (OR 5.32). Children born to a literate mother had a prevalence of only
      1.35% in relation to a corresponding value of 4.11% in children born to
      illiterate mothers (p<0.01) (OR 3.15). Birth order of preschool-age children was
      significantly related to vitamin A deficiency. In birth order less than or equal
      to three, the prevalence was 2.81%, in comparison to those with birth order four
      or more, in whom the magnitude was significantly higher (p<0.01) at 5.61% (OR
      2.08).

PMID- 18050136
TI  - The impact of meta-analyses on clinical practice: the benefits.
AB  - Meta-analyses are frequently criticized because in most cases they are compiled
      from quite heterogeneous studies. In spite of this limitation meta-analyses are
      increasingly published because in many areas of clinical research the results of
      individual studies are devoid of statistical power and end up with conflicting
      results. Meta-analyses, if performed with a rigorous and exhaustive search of all
      accountable information on a specific topic, have the potential of overcoming the
      drawbacks of single studies and, in addition, of adjusting for publication bias
      and interstudy variability. These strengths of meta-analyses can be exploited to
      provide conclusive answers on diagnostic and therapeutic issues being debated,
      which in turn may help guide doctors toward more rational decisions.

PMID- 18050137
TI  - Therapeutic implications of recent megatrials in hypertension: in favor of new
      drugs.
AB  - Blood pressure reduction represents a key priority for any preventive strategy in
      hypertension. However, one of the issues that has been raised repeatedly over the
      last few years is whether blood pressure reduction is all that matters in the
      treatment of hypertension, or if other properties related to antihypertensive
      drugs may be relevant for cardiovascular and renal outcomes. In this view, a long
      debate has emerged in the scientific and medical community, whether the newer
      classes of antihypertensive agents have additional properties beyond blood
      pressure control and, further, are superior to traditional antihypertensive
      drugs. The evidence accumulated over the last 20 years have consistently
      demonstrated that "new" drugs are as effective as "old" drugs in terms of blood
      pressure-lowering effect and in several clinical trials even more effective than
      old drugs on major cardiovascular outcomes. In addition, they have been
      demonstrated to effectively antagonize the progression of the hypertensive
      disease, as monitored through the development of intermediate end points.
      Finally, in view of the need for using combination therapy to effectively achieve
      blood pressure control in the clinical management of hypertension, the
      antihypertensive combinations based on new drugs, especially those using
      angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor
      blockers with a low-dose thiazide diuretic or those using calcium channel
      blockers and ACE inhibitors, are now considered more effective and safer than
      those using beta-blockers and low-dose thiazide diuretic, especially in view of
      their better metabolic profile and their better tolerability.

PMID- 18050138
TI  - Early renal dysfunctions in type 1 diabetes and pathogenesis of diabetic
      nephropathy.
AB  - Diabetic nephropathy develops in only a subgroup of patients affected by type 1
      diabetes. Once established, this complication is quite difficult to control, and
      consequently its prevention is presently considered the first target to achieve.
      As hyperglycemia has immediate effects on renal function and structure, it is
      reasonable to say that, in predisposed individuals, the pathogenesis of diabetic
      nephropathy also begins with the onset of diabetes. Two major hypotheses have
      been put forward to explain how the renal abnormalities that characterize the
      first years of diabetes - i.e., hyperfiltration and hypertrophy - will later lead
      to the appearance of microalbuminuria and end-stage renal disease. The first
      hypothesis considers hyperfiltration as the driving dysfunction and hypertrophy
      as the consequence. Conversely, the second points to proximal tubule hypertrophy
      as the starting point and hyperfiltration as the result. Whatever the case, tight
      glucose control from the very first days of disease seems to be the only
      established therapy to prevent future complications in type 1 diabetes.

PMID- 18050139
TI  - Emerging therapeutic strategies in diabetic nephropathy.
AB  - Diabetic nephropathy is one of the main causes of end-stage renal disease (ESRD)
      and is associated with elevated cardiovascular morbidity and mortality. Current
      renoprotective treatment for diabetic nephropathy includes strict glycemic and
      optimal blood pressure control, proteinuria/albuminuria reduction and the use of
      renin-angiotensin-aldosterone system (RAAS) blocking agents. However, the
      renoprotection provided by these treatments is only partial, and many patients
      still have progressive disease, thus suggesting that a more effective approach is
      urgently needed. This review examines emerging strategies for the treatment of
      diabetic nephropathy, including aggressive RAAS blockade, statins,
      pentoxifylline, glitazones, ruboxistaurin, as well as sulodexide. Pilot studies
      that used surrogate end points, mainly albuminuria, will be discussed. New
      insights suggest that treating microalbuminuric diabetic patients with statins,
      pentoxifylline, glitazones and sulodexide could be a new approach for reducing
      the incidence of clinical proteinuria. In diabetic patients with overt
      nephropathy, the administration of statins, pentoxifylline, sulodexide or
      aggressive RAAS inhibition, including RAAS dual blockade (i.e., angiotensin
      converting enzyme [ACE] inhibitors plus angiotensin receptor blockers or
      aldosterone antagonists plus ACE inhibitors or angiotensin receptor blockers),
      seems to be a promising way to preserve renal function and to prevent progression
      to ESRD. Results of ongoing, long-term trials on major renal and cardiovascular
      clinical outcomes, as well as on mortality are needed to establish whether the
      current standard of care of diabetic nephropathy might be improved with these new
      strategies.

PMID- 18050140
TI  - Treating anemia at different stages of renal disease.
AB  - Cardiovascular disease is the leading cause of the poor long-term survival of
      patients with chronic kidney disease (CKD). Anemia, which is a frequent and early
      complication of CKD, not only impairs patients' quality of life, but also is an
      independent risk factor for adverse cardiovascular outcomes. This may be due to
      its impact on cardiac function leading to the development of left ventricular
      hypertrophy. Starting from the clear association between higher hemoglobin levels
      and better outcomes found in observational surveys, a number of interventional
      studies have been designed to verify whether correcting anemia fully improves
      patient outcomes. The results have not indicated any major effect, although the
      majority of the studies were not primarily designed to test the effect of anemia
      correction on mortality. This is especially true in the case of CKD patients not
      undergoing dialysis. Many of these studies have also suffered from relatively
      short follow-up periods and from the fact that their statistical power was
      reduced because the difference in achieved hemoglobin levels between the
      experimental and control groups was often less than expected. Further studies
      aimed at better investigating the complex mechanisms underlying responsiveness to
      erythropoiesis-stimulating agents will probably help to explain the disagreement
      between observational studies and randomized clinical trials.

PMID- 18050141
TI  - The endothelium as a target in renal diseases.
AB  - The endothelium is a fundamental layer in the arterial wall both for the local
      regulation of flow to critical organs like the heart, brain and kidney, and for
      the protection of the vascular system from atherogenic insults. Inhibition of
      nitric oxide (NO) synthesis has profound effects at systemic and renal levels.
      Low NO bioavailability may occur in essential hypertension and in a variety of
      conditions associated with high cardiovascular risk. High oxidative stress and
      low availability of the substrate of NO-synthase, l-arginine, as well as an
      increase of endogenous NO inhibitors such as asymmetric dimethylarginine (ADMA)
      may engender endothelial dysfunction. This alteration is very frequent in
      patients with chronic kidney disease (CKD) and may contribute to accelerated
      progression of CKD, hypertension and cardiovascular complications. The kidney not
      only reabsorbs but also synthesizes l-arginine and appears to be a central organ
      for the catabolism of ADMA, mainly because it is richly endowed with the enzyme
      that degrades ADMA, dimethylarginine dimethylaminohydrolase (DDAH). Recent
      studies demonstrated that ADMA accumulation predicts both progression to end
      stage renal disease and death in patients with CKD, again further suggesting that
      ADMA is a potentially important treatment target in clinical trials aimed at
      reducing the rate of loss of renal function in these patients.

PMID- 18050142
TI  - Therapeutic implications of recent megatrials: in favor of old drugs.
AB  - Data from controlled clinical studies comparing active drugs versus placebo or
      comparing different classes of drugs and their meta-analysis seem to indicate
      that although more subtle differences in the effects of various antihypertensive
      drugs cannot be ruled out, the protective effects against cardiovascular
      morbidity and mortality of all classes of drugs, including conventional therapy
      based on diuretics and beta-blockers and their combination, are largely explained
      by the extent of blood pressure (BP) reduction. Therefore BP control is still the
      main target of antihypertensive therapy. The benefits of diuretics have been well
      documented, particularly when these drugs are used at appropriate and/or optimal
      doses to achieve the optimal antihypertensive effect with the least occurrence of
      side effects, including negative metabolic effects. Therefore they must still be
      included among first line antihypertensive drugs. By contrast, beta-blockers seem
      recently to have lost their previously favored status as initial therapy for
      hypertension owing to their lower preventive effects against cardiovascular
      events as compared with diuretics in elderly hypertensive patients and against
      stroke as compared with other treatments, and to their negative metabolic
      effects. However, although evidence-based data must be taken into account, the
      choice of antihypertensive therapy aimed at BP control in individual patients
      must be made according to clinical characteristics. We believe that a wide range
      of choices among various antihypertensive drugs, above all diuretics and also
      beta-blockers, offers an appropriate possibility of selecting the right drug and
      the right combinations according to the clinical profile of the individual
      patient.

PMID- 18050143
TI  - Arterial stiffness: a new surrogate end point for cardiovascular disease?
AB  - Measurement of arterial stiffness is assuming an increasing role in the clinical
      assessment of patients. Indeed, arterial stiffness and wave reflections are now
      well accepted as the most important determinants of increasing systolic and pulse
      pressure in our aging community, and thus as the cause of cardiovascular (CV)
      complications and events, including stroke and myocardial infarction. Carotid
      femoral pulse wave velocity (PWV), which is a direct measure of arterial
      stiffness, is the gold standard, since it requires little technical expertise and
      is supported by the greatest amount of epidemiological evidence. Indeed, aortic
      stiffness has independent predictive value for all-cause and CV mortality, CV
      disease, fatal and nonfatal coronary events and fatal strokes in patients with
      various levels of CV risk. Carotid pulse pressure and augmentation index are only
      indirect, surrogate measures of arterial stiffness. However, they provide
      additional information concerning wave reflections. They have demonstrated their
      predictive value in patients with end-stage renal disease (ESRD). Carotid
      stiffness was predictive of CV events in a small number of patients with ESRD or
      following renal transplantation, but had no independent predictive value in a
      larger number of patients with manifest arterial disease or in the healthy
      elderly patients of the Rotterdam study. To be not only an intermediate end point
      but also a surrogate end point, aortic stiffness has to demonstrate that its
      attenuation has an effect on CV mortality, coronary events and stroke. This
      remains to be established in populations at low to medium CV risk Eth i.e., with
      hypertension, dyslipidemia, diabetes and moderate chronic kidney disease.

PMID- 18050144
TI  - Improving cardiovascular risk stratification: the case for redefining
      microalbuminuria.
AB  - Large epidemiological studies have pointed out that regardless of the degree of
      hypertension, the cost-effectiveness of antihypertensive treatment increases in
      parallel with the global burden of risk. Therefore, there has been growing
      interest in developing sensitive and easy-to-perform ways to accurately and
      inexpensively identify patients at high cardiovascular risk. Numerous studies
      over the past years have provided evidence that microalbuminuria is a concomitant
      of extrarenal signs of hypertensive organ damage, as well as a strong,
      independent predictor of cardiovascular and cerebrovascular events. Recent
      clinical data indicate that the risk of cardiovascular morbidity and mortality is
      linearly related to the degree of urinary albumin excretion, with no identifiable
      threshold or plateau. Furthermore, it has been demonstrated that a reduction in
      albuminuria under antihypertensive treatment is paralleled by changes in
      cardiovascular risk. Therefore, the routine search for microalbuminuria could
      lead to a significant improvement in the evaluation and treatment of patients
      with primary hypertension.

PMID- 18050145
TI  - Microalbuminuria, endothelial dysfunction and inflammation in primary
      hypertension.
AB  - We investigated the relationship between microalbuminuria (an indicator of
      systemic and renal endothelial dysfunction), inflammation (high-sensitivity C
      reactive protein [CRP]) and endothelial function (hemodynamic response to
      acetylcholine [ACh] in the forearm) in 110 never-treated subjects with
      uncomplicated essential hypertension and serum creatinine within the normal
      range. Microalbuminuria was associated with the hemodynamic response to ACh
      (r=0.27, p=0.006) and with serum creatinine (r=0.34, p<0.001), and these
      associations held true in multivariate analyses. On the other hand,
      microalbuminuria was largely independent of serum CRP. Since microalbuminuria,
      response to ACh and serum CRP are all considered risk factors for renal
      insufficiency and since these factors were significantly related to creatinine at
      univariate analysis, we tested their association with creatinine in a multiple
      regression model including also the full set of Framingham risk factors. In this
      analysis, serum CRP and microalbuminuria maintained a significant association
      with serum creatinine, while the hemodynamic response to ACh lost substantial
      predictive value for serum creatinine. In conclusion, microalbuminuria in
      essential hypertension is weakly related to the vasodilatory response to ACh and
      unrelated to inflammation but maintains an independent link with serum
      creatinine. Collectively, these associations suggest that microalbuminuria
      reflects a local (renal) endothelial dysfunction and that it may contribute to
      renal impairment independently of inflammation and hemodynamic endothelial
      dysfunction in hypertensive patients.

PMID- 18050146
TI  - Blood pressure load, vascular permeability and target organ damage in primary
      hypertension.
AB  - BACKGROUND: Target organ damage (TOD) is an often reversible subclinical
      condition that may precede major cardiovascular events in primary hypertensive
      patients. Furthermore, TOD has been shown to be a complex, multifactorial process
      which does not depend on blood pressure (BP) reduction alone. We therefore
      investigated the relationship between BP load, vascular permeability and the
      occurrence of TOD. PATIENTS AND METHODS: Thirty-seven never-treated, nondiabetic
      hypertensive patients were enrolled. Albuminuria was measured as the albumin to
      creatinine ratio (ACR), left ventricular mass index (LVMI) was assessed by
      echocardiography, systemic vascular permeability was evaluated by transcapillary
      escape rate of albumin (TERalb), and BP was measured by means of 24-hour
      ambulatory BP monitoring. RESULTS: Patients with microalbuminuria showed higher
      levels of body mass index (BMI) (p<0.034), 24-hour systolic BP levels (p<0.001),
      left ventricular mass index (LVMI) (p=0.003) and capillary permeability to
      albumin (p<0.005), as compared with normoalbuminurics. Increased BP load and
      vascular permeability were associated with higher LVMI (p=0.012) and with an
      increased risk of having microalbuminuria and/or left ventricular hypertrophy
      (Chi square=17.4; p<0.001). Logistic regression analysis showed that the risk of
      having at least 1 sign of TOD was 10-fold higher in patients with TERalb above
      the median, and almost 5-fold higher for each 10 mm Hg increase in systolic blood
      pressure. CONCLUSIONS: Abnormal vascular permeability and increased BP load are
      potentially modifiable risk factors that are independently associated with the
      development of subclinical cardiac and renal damage.

PMID- 18050147
TI  - The adoption of hospital information systems.
AB  - This paper empirically examines the diffusion of hospital information systems
      (ISs), specifically, pharmacy, laboratory, and radiology systems. Given the
      policy significance of health IS and the widespread perception that it's
      diffusion is slow, a better understanding of the mechanisms driving IS adoption
      is needed. A novel data set incorporating both IS adoption and hospital
      characteristics was constructed. These data follow the behavior of 1965 hospitals
      for the years 1990-2000. Hypotheses pertaining to hospital characteristics,
      hospital competition, and strategic behavior are tested utilizing proportional
      hazard models. I find that IS adoption is related to multi-hospital system
      membership, payer mix, and hospital scale. The role of scale, however,
      significantly diminishes throughout the time period, likely reflecting improved
      personal computer performance and improved IT scalability. Conversely, I find
      little that strategic behavior or hospital competition affects IS adoption.
      Likewise, hospital ownership does not affect the adoption of these systems.
      Overall, these results suggest that hospital IS diffusion has not been
      normatively slow.

PMID- 18050148
TI  - Hospital costs estimation and prediction as a function of patient and admission
      characteristics.
AB  - The present work analyzed the association between hospital costs and patient
      admission characteristics in a general public hospital in the city of Rio de
      Janeiro, Brazil. The unit costs method was used to estimate inpatient day costs
      associated to specific hospital clinics. With this aim, three "cost centers" were
      defined in order to group direct and indirect expenses pertaining to the clinics.
      After the costs were estimated, a standard linear regression model was developed
      for correlating cost units and their putative predictors (the patients gender and
      age, the admission type (urgency/elective), ICU admission (yes/no), blood
      transfusion (yes/no), the admission outcome (death/no death), the complexity of
      the medical procedures performed, and a risk-adjustment index). Data were
      collected for 3100 patients, January 2001-January 2003. Average inpatient costs
      across clinics ranged from (US$) 1135 [Orthopedics] to 3101 [Cardiology]. Costs
      increased according to increases in the risk-adjustment index in all clinics, and
      the index was statistically significant in all clinics except Urology, General
      surgery, and Clinical medicine. The occupation rate was inversely correlated to
      costs, and age had no association with costs. The (adjusted) per cent of
      explained variance varied between 36.3% [Clinical medicine] and 55.1% [Thoracic
      surgery clinic]. The estimates are an important step towards the standardization
      of hospital costs calculation, especially for countries that lack formal hospital
      accounting systems.

PMID- 18050149
TI  - Interventions to improve recall of medical information in cancer patients: a
      systematic review of the literature.
AB  - This systematic review investigates which interventions are effective to improve
      recall of medical information in cancer patients. A literature research was done
      in PubMed, PsychINFO, CINAHL and Cochrane Library, following the guidelines of
      the Cochrane Collaboration. The methodological quality of selected studies was
      assessed independently by two reviewers. The results were synthesized with a Best
      Evidence Synthesis. Of initially 5173 found publications, 10 met all selection
      criteria. The results indicate that an audiotape of the patients' own
      consultation has added value upon oral information only. However, providing
      patients with a general audiotape does not improve recall of information and
      might even inhibit patients' recall. Furthermore, there is scientific evidence,
      although limited, that the use of a question prompt sheet (QPS) has a positive
      effect on recall of information, provided that the physician actively endorses
      this sheet. No evidence was found for an effect of providing patients with a
      summary letter of the consultation on recall, although research on this subject
      is scarce. In conclusion, the review suggests that interventions that are
      tailored to the individual cancer patient, such as an audiotape of the
      consultation or a QPS, are most effective. Further research needs to be done to
      establish robust results.

PMID- 18050150
TI  - Pharmaceutical expenditure, total health-care expenditure and GDP.
AB  - This paper analyses the evolution of pharmaceutical expenditure with respect to
      GDP for a group of the most important OECD economies. We find that this
      relationship is not stable across the sample considered (1960-2003), and
      heterogeneity is found in the temporal evolution of the variables and across
      countries. Furthermore, we can see differences in the income elasticity
      estimation when we disaggregate pharmaceutical expenditure into its private and
      government components or when the total health-care expenditure (Total HCE) is
      disaggregated into its pharmaceutical and non-pharmaceutical components. We
      conclude that the changes in the elasticity of pharmaceutical expenditure and in
      the Total HCE elasticity are due to the private component and the pharmaceutical
      expenditure behaviour, respectively.

PMID- 18050151
TI  - Ignorability and stability assumptions in neighborhood effects research.
AB  - Two central assumptions concerning causal inference in the potential outcomes
      framework for estimating neighborhood effects are examined. The stable unit
      treatment value assumption in the context of neighborhood effects requires that
      an individual's outcome does not depend on the treatment assigned to
      neighborhoods other than the individual's own neighborhood. The assumption is
      important in that it makes estimation feasible, although some progress can be
      made even when the assumption is relaxed. Some discussion is given concerning the
      contexts in which the neighborhood-level stable unit treatment value assumption
      is likely to hold. The ignorability assumption allows the researcher to move from
      conclusions about association to conclusions about causation. In the context of
      neighborhood-wide interventions, the ignorability assumption for the individual
      level potential outcomes framework can be easily adapted for neighborhood
      effects.

PMID- 18050152
TI  - Extending social health insurance to the informal sector in Kenya. An assessment
      of factors affecting demand.
AB  - This paper contributes to analysing and understanding the demand for (social)
      health insurance of informal sector workers in Kenya by assessing their
      perceptions and knowledge of and concerns regarding health insurance and the
      Kenyan National Hospital Insurance Fund (NHIF). It serves to explore how informal
      sector workers could be integrated into the NHIF. To collect data, focus group
      discussions were held with organized groups of informal sector workers of
      different types across the country, backed up by a self-administered
      questionnaire completed by heads of NHIF area branch offices. It was found that
      the most critical barrier to NHIF enrollment is the lack of knowledge of informal
      sector workers about the NHIF, its enrollment option and procedures for informal
      sector workers. Inability to pay is a critical factor for some, but people were,
      in principle, interested in health insurance, and thus willing to pay for it. In
      sum, the mix of demand-side determinants for enrolling in the NHIF is not as
      complex as expected. This is good news, as these demand-side determinants can be
      addressed with a well-designed strategy, focusing on awareness raising and
      information, improvement of insurance design features and setting differentiated
      and affordable contribution rates.

PMID- 18050153
TI  - The impact of cancer and quality of life for long-term survivors.
AB  - This study reports on health status and quality of life (QOL) outcomes in long
      term cancer survivors, and potential correlates including cancer type, age at
      diagnosis, health status, and key sociodemographic variables. METHOD: One hundred
      and ninety-three cancer survivors 5-10 years post-diagnosis completed a mailed
      survey assessing physical and mental health status, QOL, post-traumatic growth,
      and impact of cancer (IOC). RESULTS: Respondents were comparable to population
      norms on physical and mental health status. After controlling for
      sociodemographic and medical status variables, older respondents reported better
      overall QOL (p=0.004) and mental health (p<0.001), but worse physical health
      (p=0.04). Survivors reporting low income (p=0.02) and comorbidities (p=0.003)
      indicated worse physical functioning. A higher negative IOC score was associated
      with worse physical functioning (p<0.0001), worse mental health (p<0.0001), and
      lower overall QOL (p<0.0001). A higher positive IOC score was associated with
      better mental health (p=0.0004) and better overall QOL (p=0.005). CONCLUSION:
      Perceptions of how cancer has affected survivors' lives in both positive and
      negative ways may influence, or be influenced by, their functional abilities and
      QOL.

PMID- 18050154
TI  - INCA: new statistic for estimating the number of clusters and identifying
      atypical units.
AB  - This paper presents a solution to two problems that arise in the classification
      of data such as types of tumor, samples of gene expression profiles or general
      biomedical data. First, to estimate the real number of clusters in a data set and
      second to decide whether a new unit belongs to one of these previously identified
      clusters or it is an outlier or atypical unit. We propose a new statistic which
      allows us to solve these problems. As our approach is based on a measure of
      distance or dissimilarity between any pair of units, it can be applied to any
      kind of multivariate data (continuous, binary or multi-attribute data) and it has
      applications in many biomedical fields. We validated the approach in simulated
      examples and applied it to the diagnosis of dermal diseases and to the analysis
      of lymphatic cancer data, showing the good performance of our approach.

PMID- 18050155
TI  - Neurostatistics: applications, challenges and expectations.
AB  - Brain function and its relations to cognition and behavior can be elucidated only
      by the use of various complementary methods. Over the past 20 years, we have been
      studying the brain mechanisms underlying spatial processes using different
      methods, including the recording of single cell activity in behaving monkeys,
      functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in
      human subjects, all performing the same tasks. These methods provide partially
      overlapping perspectives, resulting in a gain in knowledge beyond the province of
      the individual method. A common aspect in this endeavor is the statistical
      analysis of the data acquired by different methods, especially regarding the
      encoding of information in unitary elements (single cell activity in
      neurophysiology, blood oxygenation level-dependent (BOLD) activation of voxels in
      fMRI, magnetic field strength in MEG) and the decoding of information from
      ensembles. In this paper we illustrate the various approaches, their data
      analysis and possible applications to medicine in the context of operations in
      space.

PMID- 18050156
TI  - 14N NQR study of nicotinamide and related compounds.
AB  - 14N nuclear quadrupole resonance (NQR) frequencies have been measured in
      picolinamide, nicotinamide, isonicotinamide, 2,6-pyridine dicarboxamide, and
      acetamide by double resonance. The 14N NQR spectra in picolinamide, nicotinamide,
      isonicotinamide, and 2,6-pyridine dicarboxamide show the presence of two distinct
      nitrogen positions: the ring position with the quadrupole coupling constant about
      4,5 MHz and the amide position with the quadrupole coupling constant about 2.6
      MHz. The NQR data are related to the structure of the investigated compounds and
      to the N--H...O hydrogen bonds.

PMID- 18050161
TI  - New EU regulations: towards biosecurity but not censorship.

PMID- 18050162
TI  - Running to stand still: BCR-like signaling suppresses type I IFN responses in
      pDC.
AB  - Plasmacytoid dendritic cells (pDC) specialize in the secretion of type I
      interferon (IFN). Although multiple pathways that modulate type I IFN responses
      have been described they are inadequately defined. In this issue of the European
      Journal of Immunology, evidence for a B cell receptor (BCR)-like signaling
      cascade in pDC that suppresses type I IFN production is provided.

PMID- 18050163
TI  - Autoreactive B cells get activated in extrafollicular sites.
AB  - Autoreactive B cells are prevented from producing autoantibodies that may cause
      pathogenicity in autoimmune diseases by the induction of tolerance. When
      autoreactive B cells escape regulation in autoimmune-prone individuals, large
      amounts of autoantibodies are produced with somatic mutations in their variable
      regions. In this issue of the European Journal of Immunology, a new and very
      useful model is presented that induces activation and hypermutation of
      autoreactive B cells upon injection of chromatin-containing immune complexes. The
      differentiation and hypermutation of autoreactive B cells takes place at
      extrafollicular sites.

PMID- 18050165
TI  - Vasculitides associated with malignancies: analysis of sixty patients.
AB  - OBJECTIVE: To describe characteristics and outcomes of vasculitides associated
      with malignancies. METHODS: The requirement for inclusion in this retrospective,
      10-year study was development of vasculitis in patients with a progressing
      malignancy. Malignancies secondary to immunosuppressants used to treat vasculitis
      were excluded. The main characteristics of vasculitides were analyzed and
      compared according to the type of malignancy. RESULTS: Sixty patients were
      included (male/female sex ratio 2.53, mean age 62.4 years). Mean followup
      duration was 45.2 months. Vasculitides were cutaneous leukocytoclastic (45%),
      polyarteritis nodosa (36.7%), Wegener's granulomatosis (6.7%), microscopic
      polyangiitis (5%), and Henoch-Schonlein purpura (5%). Malignancies were
      distributed as follows: hematologic in 63.1%, myelodysplastic syndrome (MDS) in
      32.3%, lymphoid in 29.2%, and solid tumor in 36.9%. Vasculitides were diagnosed
      concurrently with malignancy in 38% of the cases. Manifestations of vasculitides
      were fever (41.7%), cutaneous involvement (78.3%), arthralgias (46.7%),
      peripheral neuropathy (31.7%), renal involvement (23.3%; 11.7%
      glomerulonephritis, 11.7% microaneurysms, 6.7% renal insufficiency), and
      antineutrophil cytoplasmic antibody (20.4%). Vasculitis treatments were
      corticosteroids (78.3%) and immunosuppressant(s) (41.7%). Vasculitis was cured in
      65% of patients, but 58.3% died, with 1 death secondary to vasculitis.
      Independent of subtype, patients with vasculitides associated with MDS more
      frequently had renal manifestations (P = 0.02) and steroid dependence (P = 0.04)
      and achieved complete remission less often (P = 0.04) than patients with
      vasculitides associated with other malignancies. Patients with vasculitides
      associated with a solid tumor more frequently had peripheral neurologic
      involvement (P = 0.05). Patients with vasculitides associated with lymphoid
      malignancy had less frequent arthralgias (P = 0.01) and renal involvement (P =
      0.02). CONCLUSION: Vasculitides occurring during malignancies present distinctive
      features according to the vasculitis subtype and nature of the malignancy.

PMID- 18050166
TI  - Atherosclerosis in patients with biopsy-proven giant cell arteritis.
AB  - OBJECTIVE: To examine the presence of atherosclerosis in a series of giant cell
      arteritis (GCA) patients attended to in a community hospital and to determine
      whether clinical features or steroid therapy might be associated with the
      development of atherosclerotic disease. METHODS: Forty consecutive patients
      diagnosed with biopsy-proven GCA, periodically followed at the rheumatology
      outpatient clinic of Hospital Xeral-Calde, Lugo (Spain), who had ended steroid
      therapy and had at least 3 years of followup were assessed for the presence of
      atherosclerosis by determination of the carotid intima-media thickness (IMT) and
      carotid plaques using high-resolution B-mode ultrasound. Forty matched controls
      were also studied. RESULTS: GCA patients exhibited less carotid artery IMT than
      did matched controls (mean +/- SD 1.01 +/- 0.16 mm versus 1.13 +/- 0.20 mm; P =
      0.005; difference in means 0.12, 95% confidence interval 0.04-0.20). Patients who
      required steroid therapy for >2 years had greater mean +/- SD carotid IMT (1.04
      +/- 0.17 mm versus 0.95 +/- 0.15 mm) but the difference was not statistically
      significant (P = 0.10). A positive correlation between age at the time of the
      study and the carotid artery IMT in GCA patients was observed (r = 0.673, P <
      0.001). However, adjusting for age, sex, and classic atherosclerosis risk
      factors, no significant correlation between carotid IMT and the routine
      laboratory markers of inflammation assessed at the time of disease diagnosis,
      disease duration, or cumulative prednisone dose was found. CONCLUSION: The
      present study demonstrates that atherosclerotic macrovascular disease is not
      increased in patients with GCA.

PMID- 18050167
TI  - A systematic review of secondary thromboprophylaxis in patients with
      antiphospholipid antibodies.
AB  - OBJECTIVE: To systematically review the efficacy and safety data of different
      therapeutic approaches in patients with antiphospholipid antibodies (aPL) and
      thrombosis. METHODS: The Medline database and references from selected reports
      and review articles were used. Randomized controlled trials, prospective and
      retrospective cohort studies, and subgroup analysis (n > 15) that focused on the
      secondary thromboprophylaxis in patients with aPL were selected. RESULTS: Sixteen
      studies were selected. Patients with venous events and a single test for aPL
      showed a low recurrence rate while receiving oral anticoagulation at a target
      international normalized ratio (INR) of 2.0-3.0. Patients with stroke and a
      single positive aPL test had no increased risk compared with those without aPL.
      Recurrence rates in patients with definite antiphospholipid syndrome (APS) and
      previous venous thromboembolism were lower than in patients with arterial and/or
      recurrent events, both with and without therapy. Only 3.8% of recurrent events
      occurred at an actual INR >3.0. Mortality due to recurrent thrombosis was higher
      than mortality due to bleeding (18 patients versus 1 patient reported).
      CONCLUSION: For patients with definite APS, we recommend prolonged warfarin
      therapy at a target INR of 2.0-3.0 in APS patients with first venous events and
      >3.0 for those with recurrent and/or arterial events. For patients with venous
      thromboembolism or stroke and a single positive aPL test, we recommend further
      testing to determine if they have a persisting antibody. If they do not, the same
      therapy as for the general population should be used (warfarin at a target INR of
      2.0-3.0 and low-dose aspirin, respectively).

PMID- 18050168
TI  - Hypomagnesemia associated with chondrocalcinosis: a cross-sectional study.
AB  - OBJECTIVE: To determine an association between magnesium (Mg) depletion and
      chondrocalcinosis, which has been reported but not investigated in a cross
      sectional study. METHODS: Prevalence of chondrocalcinosis was investigated in 144
      individuals: 72 patients receiving home parenteral nutrition (HPN) compared with
      72 age- and sex-matched controls. Presence of chondrocalcinosis was assessed by
      knee radiographs. Blood serum and globular Mg levels and 24-hour urinary Mg
      content were compared. RESULTS: Mean +/- SD age for both patients and controls
      was 51 +/- 17 years, and 51% in both groups were women. Mean duration of HPN was
      6.4 years. Prevalence of chondrocalcinosis was markedly higher in patients
      receiving HPN than controls (16.6% versus 2.7%; P = 0.006, odds ratio [OR] 7.0,
      95% confidence interval [95% CI] 1.45-66.1). Mean +/- SD serum and globular Mg
      levels were significantly lower in patients than controls (serum: 0.75 +/- 0.09
      mmoles/liter versus 0.81 +/- 0.08 mmoles/liter, P = 0.0006; globular Mg: 1.8 +/-
      0.31 mmoles/liter versus 2.0 +/- 0.35 mmoles/liter, P = 0.0003). Twenty-four-hour
      urinary Mg level was lower in patients than controls (mean +/- SD 3.85 +/- 1.50
      mmoles versus 5.37 +/- 3.71 mmoles; P = 0.001). Prevalence of chondrocalcinosis
      was significantly higher in patients with a low serum Mg level (OR 13.5, 95% CI
      2.76-127.3, P < 0.0001), with a similarly high but not significant occurrence of
      chondrocalcinosis in patients with a low globular Mg level (OR 4.09, 95% CI 0.603
      20.26, P = 0.08) and in patients with a low 24-hour urinary Mg level (OR 3.9, 95%
      CI 0.77-16.34, P = 0.05). CONCLUSION: Long-lasting Mg depletion is strongly
      associated with chondrocalcinosis.

PMID- 18050169
TI  - Osteoporosis disease management for fragility fracture patients: new
      understandings based on three years' experience with an osteoporosis care
      service.
AB  - OBJECTIVE: To review the 3-year performance of an established osteoporosis care
      service and consider further improvements in an effort to reduce fragility
      fractures. METHODS: Osteoporosis care has been coordinated for all willing and
      able patients with orthopedic fragility fractures in our health system by a nurse
      and medical director since 2003, using a guideline-based care algorithm and task
      management software. Patients were followed by telephone for 2 years to monitor
      their status and optimize adherence to treatment. Demographics, management
      recommendations, clinical data, and adherence to treatment were reviewed for the
      2003-2005 patient population. RESULTS: Of 1,019 patients with fragility
      fractures, 61% underwent osteoporosis evaluation and treatment. The remainder
      included 15% who refused to participate and 24% who were unable to participate
      for various logistical and health reasons. More patients age >80 years were
      unwilling or unable to participate. Bone densities (dual x-ray absorptiometry
      [DXA]) were normal, low, or osteoporotic in 24%, 55%, and 21% of patients,
      respectively, and 60% of the osteoporotic group had > or = 1 abnormal metabolic
      bone laboratory result. Only 17% of the total reported a previous fracture, and
      47% had ever undergone DXA. Few experienced bone loss, a new fracture, or
      bisphosphonate intolerance during treatment. CONCLUSION: An osteoporosis care
      service has coordinated care for every willing and able fragility fracture
      patient with positive outcomes. In addition, the results suggest a high priority
      for earlier proactive diagnosis and intervention of the at-risk population if
      fractures are to be reduced.

PMID- 18050170
TI  - High titer of anti-phosphatidylserine-prothrombin complex antibodies in patients
      with cutaneous polyarteritis nodosa.
AB  - OBJECTIVE: To investigate possible correlations between cutaneous polyarteritis
      nodosa (CPN) and antiphospholipid syndrome-associated antibodies. METHODS:
      Sixteen patients were referred with CPN features. To investigate the possible
      role of antiphospholipid antibodies (aPL) in CPN, we measured serum lupus
      anticoagulant (LAC), IgG and IgM anticardiolipin (aCL) and anti
      phosphatidylserine-prothrombin complex (anti-PS/PT) antibodies, and anti-beta(2)
      glycoprotein I-dependent cardiolipin (anti-beta(2)GPI/CL) antibodies in the 16
      CPN patients, 8 microscopic polyangiitis (MPA) patients, 33 systemic lupus
      erythematosus (SLE) patients, and 23 healthy controls. LAC was determined
      according to the Subcommittee on Lupus Anticoagulant/Phospholipid Dependent
      Antibody guidelines. Anti-PS/PT, aCL, and anti-beta(2)GPI/CL antibodies were
      measured by enzyme-linked immunosorbent assay. RESULTS: Anti-PS/PT antibodies
      and/or LAC were detected in all CPN patients, but not in any controls. Serum IgM
      anti-PS/PT antibody was found in 13 (81.3%) CPN patients. The mean +/- SD serum
      anti-PS/PT IgM level (19.9 +/- 12.4 units/ml) in CPN patients was significantly
      elevated compared with SLE patients (5.7 +/- 5.9 units/ml). IgG anti-PS/PT
      antibody was detected in 5 (31.3%) CPN patients, but not in any controls. The IgG
      PS/PT antibody titers were similar in CPN patients (12.3 +/- 12.0 units/ml) and
      SLE patients (13.8 +/- 14.3 units/ml). Three (18.8%) CPN patients were positive
      for IgG aCL antibody and 2 (12.5%) for IgM aCL antibody. No MPA patients had aPL.
      CPN skin manifestations included livedo reticularis (14 [87.5%]). Direct
      immunofluorescence (DIF) revealed C3 within the affected vessels in 7 (77.8%) of
      9 CPN patients. CONCLUSION: Our study demonstrated that presence of anti-PS/PT
      antibodies and/or LAC could serve as markers in CPN patients. CPN could be
      dependently associated with the presence of anti-PS/PT antibody. Clinicians need
      to recognize these titers to permit early accurate diagnosis and treatment. We
      believe that anti-PS/PT antibodies will become widely recognized as a new factor
      when diagnosing CPN.

PMID- 18050171
TI  - Treatment of refractory polymyalgia rheumatica with etanercept: an open pilot
      study.
AB  - OBJECTIVE: To investigate whether etanercept has a steroid-sparing effect in the
      treatment of patients with relapsing polymyalgia rheumatica (PMR). METHODS: The
      study group comprised patients with relapsing PMR who were not able to reduce
      their prednisone dosage below 7.5-10 mg/day and who had experienced
      corticosteroid-related side effects. Patients received injections of etanercept
      25 mg twice weekly for 24 weeks, and were followed up for 3 additional months
      after treatment withdrawal. Patients regularly underwent clinical assessment,
      measurement of erythrocyte sedimentation rate and C-reactive protein level, and
      ultrasound (US) examination of the shoulders during the 9 months of the followup
      period. RESULTS: All 6 enrolled patients responded to etanercept with sustained
      remission (improvement of at least 70% according to European League Against
      Rheumatism response criteria for PMR in 4 patients and at least 50% in 2
      patients) and were able to significantly reduce their median prednisone daily
      dosage without experiencing a disease relapse (8.75 mg versus 2.5 mg; P = 0.026)
      at the end of the 9-month study period. US shoulder examination performed at the
      end of followup demonstrated a parallel reduction of glenohumeral and
      periarticular inflammation. A significant reduction in the cumulative prednisone
      dose 9 months before versus the 9-month study period was observed (mean +/- SD
      1,767 +/- 524 mg versus 730 +/- 182 mg; P = 0.028). Three patients developed
      nonsevere side effects: bacterial cystitis in 2 and influenza in 1. CONCLUSION:
      These results, which should be confirmed in a controlled study, suggest that
      etanercept may be a safe and useful corticosteroid-sparing agent in relapsing
      PMR.

PMID- 18050172
TI  - Diagnostic and prognostic relevance of neuromuscular biopsy in primary Sjogren's
      syndrome-related neuropathy.
AB  - OBJECTIVE: To evaluate the clinicobiologic presentation in patients with primary
      Sjogren's syndrome (SS)-related peripheral neuropathy, the histologic results of
      neuromuscular biopsy (NMB), and clinical outcome, and to identify prognostic
      factors. METHODS: We retrospectively studied clinical and biologic presentation
      of 40 patients with primary SS-related neuropathy who underwent NMB. Prognostic
      factors of clinical outcome were assessed by univariate and multivariate
      analysis. RESULTS: Patients with vasculitis (lymphocytic [n = 8] or necrotizing
      [n = 14]) had a higher prevalence of acute-onset neuropathy, multiple
      mononeuropathy, sensorimotor involvement, vascular purpura, general symptoms,
      increased C-reactive protein level, positivity for rheumatoid factor,
      hypocomplementemia, and monoclonal gammopathy compared with those without
      vasculitis (n = 18). Comparison between patients with necrotizing or lymphocytic
      vasculitis did not reveal significant differences in clinical or biologic
      presentation except for the presence of general symptoms and rheumatoid factor.
      Regarding clinical evolution, the results of NMB (P < 0.0001), in particular the
      presence of necrotizing vasculitis (P < 0.001), an acute neuropathy onset (P <
      0.0001), general symptoms (P < 0.0001), multiple mononeuropathy (P = 0.0007),
      presence of sensorimotor involvement (P = 0.002), and increased C-reactive
      protein level (P = 0.008), were significantly associated with a better outcome in
      univariate analysis. In multivariate analysis, NMB resulting in the
      identification of patients with necrotizing vasculitis was the only variable that
      remained significantly associated with a better outcome (P = 0.01). CONCLUSION:
      NMB is necessary to identify patients with necrotizing vasculitis, who have a
      better response to immunosuppressive therapy. NMB might therefore have both a
      diagnostic and prognostic relevance in primary SS-related neuropathy.

PMID- 18050173
TI  - The Rasch measurement model in rheumatology: what is it and why use it? When
      should it be applied, and what should one look for in a Rasch paper?

PMID- 18050174
TI  - Internal construct validity of the Oxford Knee Scale: evidence from Rasch
      measurement.
AB  - OBJECTIVE: Symptomatic knee osteoarthritis (OA) is present in 1 in 8 patients age
      >60 years and is associated with significant activity limitation. Several tools
      have been devised to assess knee problems. The goal of this study was to evaluate
      the Oxford Knee Scale (OKS) against strict modern psychometric standards through
      application of the Rasch measurement model. METHODS: A total of 224 OKS
      assessments were included from patients with a clinical diagnosis of knee OA.
      Data from the OKS were fitted to the Rasch measurement model. We examined the
      validity of the item scoring functions, the presence of item bias or differential
      item functioning, the fit of data to model expectations, and whether or not the
      item set formed a unidimensional scale, thus giving a valid summed score.
      RESULTS: The mean age of the 224 patients was 61 years (range 26-90) and 61.5%
      were women. After rescoring some items, the scale showed good fit to the Rasch
      model, with a chi-square interaction statistic of 42.663 (36 df, P = 0.206).
      Overall targeting of the scale (to the patients) was good, with high reliability.
      CONCLUSION: Data from the OKS were consistent with the expectations of the
      unrestricted (partial credit) derivation of the Rasch model. The targeting of the
      instrument shows good coverage of thresholds across the whole construct and has
      good reliability (internal consistency) with a high patient separation.
      Consequently, this scale can be used in confidence with the knowledge that it is
      a unidimensional scale largely free of bias.

PMID- 18050175
TI  - Prognosis of hip pain in general practice: a prospective followup study.
AB  - OBJECTIVE: Hip pain in the elderly is the main feature of osteoarthritis of the
      hip. In this prospective followup study, we wanted to determine which patients
      with hip pain show disease progression, and what the incidence of total hip
      replacement (THR) is in this group of patients after 3 and 6 years of followup.
      METHODS: Within general practices in the area of Rotterdam (The Netherlands),
      persons age > or = 50 years with incident hip pain were included. After 3 and 6
      years, progression of hip pain was assessed. RESULTS: A total of 224 patients
      were included. After 3 years disease progressed in 29 (15%) patients and 23 (12%)
      received a THR. After 6 years disease progressed in 45 (28%) patients and 36
      (22%) received a THR. The prognostic variables for a THR after 3 and 6 years
      related to history taking were age > or = 60 years, morning stiffness, and pain
      in the groin/medial thigh; variables related to physical examination were
      decreased extension/adduction, painful internal rotation, and a body mass index <
      or = 30 kg/m(2); and the variable related to radiologic findings was a
      Kellgren/Lawrence grade of 2 or higher. CONCLUSION: In this study population,
      approximately 12% of patients presenting with hip pain to their general
      practitioner will undergo a THR within 3 years, and approximately 22% after 6
      years. Using the variables obtained from history taking, physical examination,
      and radiologic findings enables better identification of persons at high risk for
      a THR.

PMID- 18050176
TI  - Long-term outcome following total hip arthroplasty: a controlled longitudinal
      study.
AB  - OBJECTIVE: To assess long-term outcome and predictors of prognosis following
      total hip arthroplasty (THA) for osteoarthritis (OA). METHODS: We studied 282
      patients from 2 English health districts approximately 8 years after THA, along
      with 295 controls selected from the general population. Baseline data were
      collected by interview and examination, on sex, age, comorbidity, body mass index
      (BMI), and Short Form 36 (SF-36) functional status, and preoperative radiographic
      severity of OA was graded. Functional status was reassessed at followup by postal
      questionnaire. Predictors of change in physical functioning were analyzed by
      linear regression. RESULTS: Over followup, cases who had THA reported a median
      improvement of 10 points in SF-36 score for physical functioning, whereas in
      controls there was a median deterioration of 10 points (P < 0.0001). Mental
      health improved by a median of 12 points in both cases and controls. Change in
      physical functioning was significantly worse in women and at older ages among
      both cases and controls. In cases, Croft grade 5 OA was associated with a
      physical functioning score improvement 19.4 points (95% confidence interval 7.7,
      31.2) greater than the improvement in grades 0-3, but BMI was unrelated to change
      in physical functioning. CONCLUSION: Improvements in physical functioning
      following THA for OA are sustained in the long term and are more frequent in
      patients with more severe radiographic features preoperatively. We found no
      indication that patients who are overweight benefit less from THA, but further
      evidence is needed on the prognostic influence of more severe obesity.

PMID- 18050177
TI  - Factors associated with restricted mobility outside the home in community
      dwelling adults ages fifty years and older with knee pain: an example of use of
      the International Classification of Functioning to investigate participation
      restriction.
AB  - OBJECTIVE: To investigate the links between knee pain characteristics and
      restricted mobility outside the home, and how these are influenced by mobility
      specific activity limitation, age, sex, socioeconomic status, environmental
      factors, and comorbidity. METHODS: We conducted a cross-sectional survey of
      community-dwelling adults age > or = 50 years. A total of 2,252 responders
      reporting pain in and around the knee in the last year were eligible. The primary
      outcome was self-reported restricted mobility outside the home in the previous 4
      weeks (dichotomized as present or absent). RESULTS: Knee pain severity was
      strongly associated with restricted mobility outside the home, an association
      largely mediated by perceived limitation in walking. After adjusting for
      demographic and socioeconomic characteristics, individual contributions from
      selected comorbidities, knee pain severity, limitation in walking, and specific
      environmental factors remained. These environmental factors included perceived
      need of aids and assistance (adjusted odds ratio [OR] 3.1, 95% confidence
      interval [95% CI] 2.2-4.4), poor access to public transportation (adjusted OR
      2.3, 95% CI 1.4-3.9), and having no access to a car (adjusted OR 1.6, 95% CI 1.1
      2.4). CONCLUSION: There are a range of potential health and social targets that,
      if addressed, might reduce restricted mobility outside the home in middle-aged
      and older individuals with knee pain. Our results suggest that, in addition to
      treating the knee symptoms, such targets might include comorbidity, walking
      ability, and environmental barriers such as poor access to public transportation.
      Moreover, removing environmental barriers may reduce immobility outside the home
      even in the continued presence of osteoarthritis symptoms and specific activity
      limitations.

PMID- 18050178
TI  - Case management of arthritis patients in primary care: a cluster-randomized
      controlled trial.
AB  - OBJECTIVE: To assess whether providing information on arthritis self-management
      through general practitioners (GPs) increases the quality of life in patients
      with osteoarthritis and whether additional case management provided by practice
      nurses shows better results. METHODS: We conducted a pragmatic, cluster
      randomized, controlled, 3-arm trial that included 1,021 patients from 75 primary
      care practices in Germany. GPs were randomized to intervention group I, group II,
      or a control group. GPs of both intervention groups participated in 2 peer group
      meetings. In intervention group II, additional case management was conducted via
      telephone by a practice nurse. The primary outcome was change in quality of life,
      assessed by the German version of the Arthritis Impact Measurement Scales Short
      Form (AIMS2-SF). Secondary outcomes were health service utilization,
      prescriptions, and physical activity. Data were controlled for depression using
      the Patient Health Questionnaire 9 as a potential confounder. RESULTS: Of 1,125
      administered questionnaires, 1,021 were analyzed. Compared with the control
      group, no significant changes occurred in intervention group I with respect to
      the primary outcome. Performed radiographs decreased significantly (P = 0.050),
      whereas prescriptions of acetaminophen increased significantly (P < 0.001). In
      intervention group II, significant changes in the AIMS2-SF dimensions social (P <
      0.001), symptom (P = 0.048), and lower body (P = 0.049) were identified.
      Radiographs (P = 0.031) and orthopedic referrals (P = 0.044) decreased whereas
      prescriptions of pain relievers increased significantly. CONCLUSION: Improving
      the quality of life in patients with arthritis using arthritis self-management
      seems challenging. Simply providing this information through GPs is not
      sufficient but combining it with case management seems to be a promising
      approach.

PMID- 18050179
TI  - Reproducibility of the measurement of knee joint proprioception in patients with
      osteoarthritis of the knee.
AB  - OBJECTIVE: To estimate the inter- and intrarater reliability and agreement of
      instrumented knee joint proprioception measurement in subjects with knee
      osteoarthritis (OA) and healthy subjects; to assess the effect of variations in
      the measurement procedure on agreement parameters. METHODS: Proprioception was
      measured by a computer-controlled knee angular motion-detecting device in a
      movement-detecting task. The angular displacement between the starting position
      and the position at the instant of movement detection by the subject was
      recorded. Two raters independently assessed knee joint proprioception. After 14
      days the assessment was repeated. Complete data were obtained from 24 subjects
      with knee OA and 26 healthy subjects. The inter- and intrarater reliability
      coefficients (intraclass correlation coefficients [ICC]) and inter- and
      intrarater agreement measures (standard error of measurement [SEM] and minimal
      detectable difference [MDD]) were calculated. Additionally, the effect of
      changing the velocity of angular displacement and applying headphone music during
      the measurement on the absolute error (i.e., SEM and MDD) was estimated at the
      second occasion. RESULTS: Interrater reliability was good in subjects with knee
      OA and healthy subjects (ICC 0.91 and 0.89, respectively). Interrater agreement
      was higher in subjects with knee OA than in healthy subjects (SEM 2.13 degrees
      versus 0.43 degrees , MDD 5.90 degrees versus 1.19 degrees ). Intrarater
      reliability was good in subjects with knee OA and healthy subjects (ICC 0.91 and
      0.86, respectively). Intrarater agreement (SEM and MDD) was 2.26 degrees and 6.26
      degrees in subjects with knee OA and 0.39 degrees and 1.08 degrees in healthy
      subjects. The original measurement and the 2 variations in measurement showed
      comparable measurement errors for subjects with knee OA and healthy subjects.
      CONCLUSION: In knee OA subjects and healthy subjects, knee proprioception
      measurement shows adequate intra- and interreliability. However, the absolute
      measurement error is rather high. Therefore, this measurement has limited value
      in the assessment of individual subjects, but can be recommended for scientific
      research in groups of individuals.

PMID- 18050180
TI  - Health-related quality of life in women with symptomatic hand osteoarthritis: a
      comparison with rheumatoid arthritis patients, healthy controls, and normative
      data.
AB  - OBJECTIVE: Data on the burden of disease and impact on health-related quality of
      life (HRQOL) in hand osteoarthritis (OA) are limited. The goal of this study was
      to compare HRQOL in patients with hand OA with HRQOL in patients with rheumatoid
      arthritis (RA), healthy controls, and normative data from the general population.
      METHODS: A total of 190 women with hand OA were compared with 194 women with RA
      and 144 healthy women of the same age. Health status was measured using the Short
      Form 36 (SF-36), Short Form 6D (SF-6D), modified Health Assessment Questionnaire
      (M-HAQ), pain and fatigue visual analog scales, and grip strength. Scores were
      compared by analysis of variance and a multivariate analysis of covariance,
      adjusting for age, number of comorbidities, and years of education. Gaps between
      patients and population subjects were assessed by calculating S scores on all
      dimensions of the SF-36. RESULTS: Hand OA and RA patients had worse scores on all
      assessed dimensions of subjective health compared with healthy controls. RA
      patients showed poorest general health (SF-36), poorest physical function (M-HAQ,
      SF-36 physical, grip strength), and highest level of fatigue compared with hand
      OA patients. Hand OA patients reported poorer mental health. Mean utility scores
      (SF-6D) in hand OA and RA were 0.64 and 0.63, respectively, with a mean
      difference compared with healthy controls of 0.13 in hand OA and 0.14 in RA
      patients. S scores confirmed a marked disparity between individuals with a
      rheumatic diagnosis (hand OA, RA) and population subjects. CONCLUSION: This study
      illustrates that patients with hand OA experience a broad impact on HRQOL
      compared with healthy controls. Fatigue and physical function are worse in RA
      than hand OA.

PMID- 18050181
TI  - Hylan versus hyaluronic acid for osteoarthritis of the knee: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To compare the effectiveness and safety of intraarticular high
      molecular hylan with standard preparations of hyaluronic acids in osteoarthritis
      of the knee. METHODS: We performed a systematic review and meta-analysis of
      randomized controlled trials comparing hylan with a hyaluronic acid in patients
      with knee osteoarthritis. Trials were identified by systematic searches of
      Central, Medline, EMBase, Cinahl, the Food and Drug Administration, and Science
      Citation Index supplemented by hand searches of conference proceedings and
      reference lists (last update November 2006). Literature screening and data
      extraction were performed in duplicate. Effect sizes were calculated from
      differences in means of pain-related outcomes between treatment and control
      groups at the end of the trial, divided by the pooled standard deviation. Trials
      were combined using random-effects meta-analysis. RESULTS: Thirteen trials with a
      pooled total of 2,085 patients contributed to the meta-analysis. The pooled
      effect size was -0.27 (95% confidence interval [95% CI] -0.55, 0.01), favoring
      hylan, but between-trial heterogeneity was high (I(2) = 88%). Trials with blinded
      patients, adequate concealment of allocation, and an intent-to-treat analysis had
      pooled effect sizes near null. The meta-analyses on safety revealed an increased
      risk associated with hylan for any local adverse events (relative risk [RR] 1.91;
      95% CI 1.04, 3.49; I(2) = 28%) and for flares (RR 2.04; 95% CI 1.18, 3.53; I(2) =
      0%). CONCLUSION: Given the likely lack of a superior effectiveness of hylan over
      hyaluronic acids and the increased risk of local adverse events associated with
      hylan, we discourage the use of intraarticular hylan in patients with knee
      osteoarthritis in clinical research or practice.

PMID- 18050182
TI  - Delay in consultation with specialists for persons with suspected new-onset
      rheumatoid arthritis: a population-based study.
AB  - OBJECTIVE: Care in rheumatoid arthritis (RA) is optimized by involvement of
      rheumatologists. We wished to determine whether patients suspected of having new
      onset RA in Quebec consulted with a rheumatologist, to document any delay in
      these consultations, and to determine factors associated with prompt
      consultation. METHODS: Physician reimbursement administrative data were obtained
      for all adults in Quebec. Suspected new-onset cases of RA in the year 2000 were
      defined operationally as a physician visit for RA (based on the International
      Classification of Diseases, Ninth Revision diagnostic codes), where there had
      been no prior visit code to any physician for RA in the preceding 3 years. For
      those patients who were first diagnosed by a nonrheumatologist, Cox regression
      modeling was used to identify patient and physician characteristics associated
      with time to consultation with a rheumatologist. RESULTS: Of the 10,001 persons
      coded as incident RA by a nonrheumatologist, only 27.3% consulted a
      rheumatologist within the next 2.5-3.5 years. Of those who consulted, the median
      time from initial visit to a physician for RA to consultation with a
      rheumatologist was 79 days. The strongest predictors of shorter time to
      consultation were female sex, younger age, being in a higher socioeconomic class,
      and having greater comorbidity. CONCLUSION: Our data suggest that the vast
      majority of patients suspected of having new-onset RA do not receive rheumatology
      care. Further action should focus on this issue so that outcomes in RA may be
      optimized.

PMID- 18050183
TI  - Influence of -308 A/G polymorphism in the tumor necrosis factor alpha gene on
      etanercept treatment in rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether the -308 A/G tumor necrosis factor alpha
      (TNFalpha) gene polymorphism can predict the outcome of etanercept therapy in 86
      patients with rheumatoid arthritis (RA), as already observed in patients treated
      with infliximab. METHODS: Eighty-six RA patients treated with etanercept were
      genotyped for -308 A/G TNFalpha gene polymorphism by polymerase chain reaction
      and melting curve analysis, using specific gene primers and probes. Patients were
      subdivided into group A (G/A genotype) and group G (G/G genotype). We compared
      clinical responses to etanercept between groups A and G after 6 months, using the
      Disease Activity Score in 28 joints (DAS28). After 12-month treatment, 48 of 86
      patients were evaluated again. RESULTS: Of 86 patients, 18 (21%) belonged in
      group A and 68 (79%) belonged in group G. After 6-month treatment, 55.6% of
      patients in group A and 82.4% of patients in group G had DAS28 improvement >1.2
      (P = 0.027 by chi-square). The mean +/- SD DAS28 improvement was 1.69 +/- 1.31 in
      group A and 2.23 +/- 1.19 in group G (P = 0.098 by t-test). After 1-year
      treatment 48 patients were tested again: 10 (21%) belonged in group A and 38
      (79%) belonged in group G. Forty percent of patients in group A and 87% in group
      G had DAS28 improvement >1.2 (P = 0.005 by chi-square). The mean +/- SD DAS28
      improvement was 1.334 +/- 1.37 in group A and 2.29 +/- 1.47 in group G (Mann
      Whitney U test = 115, P = 0.0057). CONCLUSION: RA patients with a -308 G/G
      TNFalpha genotype respond to etanercept better than patients with a -308 A/G
      genotype.

PMID- 18050184
TI  - The risk of herpes zoster in patients with rheumatoid arthritis in the United
      States and the United Kingdom.
AB  - OBJECTIVE: To determine whether the incidence of herpes zoster is elevated in
      patients with rheumatoid arthritis (RA) and whether herpes zoster is associated
      with use of disease-modifying antirheumatic drugs (DMARDs) in patients with RA.
      METHODS: Two retrospective cohort studies were conducted using data from a US
      integrated managed care database (PharMetrics claims database) from 1998-2002 and
      the UK General Practice Research Database (GPRD) between 1990-2001. Rates of
      herpes zoster among patients with RA and randomly sampled non-RA patients were
      compared. A nested case-control analysis was performed within each RA cohort to
      examine the effect of current treatment on herpes zoster risk. RESULTS: A total
      of 122,272 patients with RA from the PharMetrics database and 38,621 from the
      GPRD were included. The adjusted hazard ratios of herpes zoster for patients with
      RA compared with non-RA patients were 1.91 (95% confidence interval [95% CI] 1.80
      2.03) in the PharMetrics database and 1.65 (95% CI 1.57-1.75) in the GPRD. In the
      PharMetrics database, current use of biologic DMARDs alone was associated with
      herpes zoster (odds ratio [OR] 1.54, 95% CI 1.04-2.29), as was current use of
      traditional DMARDs alone (OR 1.37, 95% CI 1.18-1.59). In the GPRD, current use of
      traditional DMARDs was associated with herpes zoster (OR 1.27, 95% CI 1.10-1.48).
      In both data sources, use of oral corticosteroids was associated with herpes
      zoster regardless of concomitant therapies. CONCLUSION: Data from 2 large
      databases suggested that patients with RA are at increased risk of herpes zoster.
      Among patients with RA, DMARDs and/or use of oral corticosteroids appeared to be
      associated with herpes zoster.

PMID- 18050185
TI  - Prevalence of and annual ambulatory health care visits for pediatric arthritis
      and other rheumatologic conditions in the United States in 2001-2004.
AB  - OBJECTIVE: To estimate the prevalence of and the annual number of ambulatory
      health care visits for pediatric arthritis and other rheumatologic conditions.
      METHODS: We used physician office visit, outpatient department visit, and
      emergency department visit data from the 2001-2004 National Ambulatory Medical
      Care Survey and 2001-2004 National Hospital Ambulatory Medical Care Survey to
      estimate annual visits for the International Classification of Diseases, Ninth
      Revision, Clinical Modification codes thought to represent significant pediatric
      arthritis and other rheumatologic conditions (SPARC). We converted visit
      estimates into prevalence estimates using data on the number of prior annual
      visits per patient. Synthetic estimates for states were produced using national
      rates. RESULTS: The average annualized estimate of the number of children with
      SPARC was 294,000 (95% confidence interval [95% CI] 188,000-400,000). The
      annualized number of ambulatory health care visits for SPARC was 827,000 (95% CI
      609,000-1,044,000). CONCLUSION: Pediatric arthritis estimates have varied widely
      because it is an umbrella term for which there are many definitions and because
      it is a relatively uncommon condition from a population surveillance perspective.
      Our estimates suggest that arthritis-related health care visits impose a
      substantial burden on the pediatric health care system. One advantage of this
      surveillance paradigm is that it has established a starting point for tracking
      the national prevalence of arthritis and rheumatologic conditions in children on
      an ongoing basis using existing infrastructure rather than expensive new surveys.
      This surveillance system will help us monitor and predict the health care needs
      of patients with these conditions.

PMID- 18050186
TI  - Reliability of exercise testing and functional activity questionnaires in
      children with juvenile arthritis.
AB  - OBJECTIVE: To determine the reliability of formal exercise testing and the
      reliability of functional and activity questionnaires in children with juvenile
      idiopathic arthritis (JIA). METHODS: Children with JIA of any subtype ages 8-16
      years who were recruited to a randomized trial comparing different exercise
      therapies participated in 2 preintervention sessions of exercise testing 2-6
      weeks apart. Exercise testing included 1) submaximal oxygen uptake (VO(2submax)),
      2) peak VO(2) (VO(2peak)), and 3) anaerobic power using modified Wingate tests
      (W(ant)). Two physical function questionnaires (the Childhood Health Assessment
      Questionnaire [C-HAQ] and Revised Activity Scale for Kids [ASK]) and 1 daily
      physical activity questionnaire (the Habitual Activity Estimation Scale [HAES])
      were also completed at these times. Test-retest reliability was assessed using
      type 3, intrarater intraclass correlation coefficient (ICC(3,1)) and Bland and
      Altman plots were used to determine limits of agreement. RESULTS: Data were
      available for 74 patients (58 girls). VO(2submax), VO(2peak), and W(ant)
      demonstrated high reliability (ICC(3,1) 0.82, 0.91, and 0.94, respectively). C
      HAQ and ASK questionnaires also had very high reliability (ICC(3,1) 0.82 and
      0.91, respectively). The HAES demonstrated low reliability for total activity
      score (ICC(3,1) 0.15) and moderate reliability when the number of very active
      hours was analyzed separately (ICC(3,1) 0.59). CONCLUSION: Results of this
      investigation suggest that exercise testing and functional questionnaires in
      children with JIA are consistent and reliable. Reliability of the HAES total
      score was poor, but moderate when the very active hours subscale score was used.

PMID- 18050187
TI  - Impact of memory impairment on employment status in persons with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To assess the specific contribution of memory impairment to employment
      status in persons with systemic lupus erythematosus (SLE). METHODS: A total of
      832 patients with SLE were surveyed and data collected on demographics, SLE
      symptoms and activity, health status, depression, medications, health resource
      utilization, and current employment status. Participants underwent screening for
      memory impairment and based on their scores were categorized to 3 levels of
      memory function: intact, mild-moderate impairment, and severe impairment.
      Employment status was compared across impairment levels using multivariate
      logistic regression, adjusting for sociodemographic characteristics (i.e., age,
      sex, race, education, and marital status), employment status at year of
      diagnosis, disease activity, disease duration, and depression. RESULTS: In the
      intact memory function group, 54.2% were employed, versus 40.6% in the mild
      moderate impairment group and 31.0% in the severe impairment group. In the intact
      memory function group, 29.2% were unable to work, versus 40.6% in the mild
      moderate impairment group and 56.3% in the severe impairment group. After
      multivariate adjustment, increasing levels of memory impairment predicted a
      decreased likelihood of being employed: odds ratio (OR) 0.70, 95% confidence
      interval (95% CI) 0.48-1.02 for the mild-moderate impairment group and OR 0.57,
      95% CI 0.32-1.00 for the severe impairment group. Participants with memory
      impairment were more likely to report being unable to work: OR 1.36, 95% CI 0.90
      2.04 for the mild-moderate impairment group, and OR 1.99, 95% CI 1.12-3.55 for
      the severe impairment group. These findings were statistically significant only
      in the severe impairment groups. CONCLUSION: The findings suggest that severe
      memory impairment is an important factor associated with employment status in
      persons with SLE.

PMID- 18050188
TI  - General and specific factors associated with severity of cognitive impairment in
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine factors affecting the severity of cognitive impairment in
      systemic lupus erythematosus (SLE) and to analyze its anatomic location. METHODS:
      Fifteen cognitive functions grouped into 8 domains were evaluated in 52 patients
      with SLE and 20 with rheumatoid arthritis. Patients were classified according to
      severity of impairment as normal, mild, or moderate/severe. Multivariate analysis
      was performed to identify the main factors affecting severity of cognitive
      deficits. The most likely anatomic site of damage according to neuropsychological
      performance was compared with the lesion's location on magnetic resonance imaging
      (MRI). RESULTS: In SLE patients, a stepwise regression analysis showed that the
      number of impaired functions (dependent variable) was associated with
      antiphospholipid antibody positivity (aPL+; P = 0.04), the Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology Damage Index
      (SDI; P = 0.001), hypertension (P = 0.032), and was inversely related to
      educational level (P = 0.021). Including MRI, the number of impaired functions
      was associated with severity of MRI (P < 0.001), the SDI (P = 0.013), and the
      presence of Raynaud's phenomenon (P = 0.04). The contemporary presence of aPL+
      and Raynaud's phenomenon resulted in a higher probability to develop
      moderate/severe cognitive deficits (P = 0.015). Two logistic multiple regression
      analyses identified hypertension (P < 0.05), the SDI (P < 0.01), and
      moderate/severe MRI findings as main predictors of moderate/severe impairment
      (dependent variable). The damage site hypothesized through neuropsychological
      testing corresponded with MRI findings in 71.7% of SLE patients K = 0.42, P =
      0.005). CONCLUSION: Hypertension, aPL+, accumulated damage, and MRI lesions are
      the main factors affecting severity of cognitive impairment in SLE. The
      hypothesized sites of central nervous system involvement according to
      neuropsychological testing correlated with MRI findings in most patients.

PMID- 18050189
TI  - Treatment of early rheumatoid arthritis: a randomized magnetic resonance imaging
      study comparing the effects of methotrexate alone, methotrexate in combination
      with infliximab, and methotrexate in combination with intravenous pulse
      methylprednisolone.
AB  - OBJECTIVE: To compare the effects of methotrexate (MTX), alone or in combination
      with intravenous (IV) methylprednisolone (MP) or infliximab, on magnetic
      resonance imaging (MRI)-detected synovitis, bone edema, and erosive changes in
      patients with early rheumatoid arthritis (RA). METHODS: Forty-four patients with
      early RA were randomized to receive MTX alone (MTX group), MTX plus IV MP (IV MP
      group), or MTX plus infliximab (infliximab group), infused on day 0 and weeks 2,
      6, 14, 22, 30, 38, and 46. Gadolinium-enhanced MRI scans of the
      metacarpophalangeal joints, wrists, and metatarsophalangeal joints were performed
      at baseline, week 18, and week 52. RESULTS: Scores for MRI-detected synovitis and
      bone edema improved over time in the 3 groups, with significantly lower synovitis
      scores in the infliximab group compared with the MTX group and significantly
      lower bone edema scores in the infliximab group compared with the MTX and the IV
      MP groups. Scores for MRI-detected erosion significantly increased over time in
      all groups. There were no differences in erosion scores between the MTX group and
      the other groups. It is of note that patients treated with IV MP showed more
      significant progression in MRI-detected erosions compared with patients treated
      with infliximab. At week 22, response rates according to the American College of
      Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 were
      significantly higher in both the IV MP group and the infliximab group compared
      with the MTX group. At week 52, remission was achieved in 40% of patients in the
      MTX group and in 70% of patients in the IV MP and infliximab groups. Health
      Assessment Questionnaire scores improved significantly over time in all groups,
      with patients receiving IV MP experiencing significantly more improvement
      compared with patients treated with MTX alone. No severe side effects were
      observed, except 1 case of MTX-related pneumonitis. CONCLUSION: The combination
      of MTX and infliximab is superior to MTX alone for reducing MRI-detected signs of
      synovitis and bone edema in patients with early RA. Progression of MRI-detected
      erosion was greater in patients treated with MTX plus IV MP compared with that in
      patients who received MTX plus infliximab.

PMID- 18050190
TI  - Clinical images: A rheumatoid arthritis patient with swelling of the shoulder.

PMID- 18050191
TI  - Type IV collagen alpha-chain composition in synovial lining from trauma patients
      and patients with rheumatoid arthritis.
AB  - OBJECTIVE: Normal synovial lining is composed of macrophage-like type A and
      fibroblast-like type B lining cells. This sheet-like structure lacks a basement
      membrane, but its intercellular substance contains some basement membrane
      components, including type IV collagen. We undertook this study to determine the
      alpha-chain composition of type IV collagen in normal and arthritic synovial
      lining, using monoclonal alpha-chain antibodies. METHODS: Samples were analyzed
      using avidin-biotin-peroxidase complex staining for the presence of collagen
      alpha1/2(IV), alpha3(IV), alpha4(IV), alpha5(IV), alpha6(IV), matrix
      metalloproteinase 2 (MMP-2), and MMP-9, and the enzyme activity was detected
      using gelatin zymography. Double immunofluorescence was performed for type IV
      collagen/MMP-9 and type IV collagen/CD68. Synovial fibroblasts were studied using
      quantitative reverse transcriptase-polymerase chain reaction. RESULTS: In mildly
      inflamed synovium from 5 trauma patients, alpha1/2(IV) chains were strongly
      stained, but alpha5(IV) and alpha6(IV) chains were weakly stained. Coding
      messenger RNA was shown in cultured synovial fibroblasts. Basement membranes of
      blood vessels contained all alpha(IV) chains and served as useful positive sample
      controls. In the synovial lining from 5 patients with rheumatoid arthritis (RA),
      all alpha-chains were absent/very weakly stained. This was coupled with numerous
      type A lining cells containing MMP-9 (type IV collagenase), also found in
      synovial fluid. CONCLUSION: Synovial lining has a unique and very limited alpha
      chain composition, different from that of the vascular basement membrane, which
      contains all alpha-chains. This special composition and lack of nidogen are
      probably of relevance for the bidirectional translining diffusion. Such tentative
      alpha-chain-dependent adhesive and transport-regulating properties seem to be
      deranged in RA, probably in part due to type IV collagenases produced in the
      lining and/or released by transmigrating or synovial fluid neutrophils.

PMID- 18050192
TI  - Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis
      of synovial fibroblasts.
AB  - OBJECTIVE: To compare the expression of galectin 9 (Gal-9) in synovial tissue
      (ST) from rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients and
      to evaluate the effects of Gal-9 on fibroblast-like synoviocytes (FLS) in these
      patients. METHODS: The expression of Gal-9 in ST and FLS was compared using
      immunohistochemical techniques. Apoptotic cells in RA and OA ST samples were
      detected by TUNEL assay. Apoptosis of FLS was analyzed by the sub-G(1) method in
      vitro. The in vivo suppressive effects of Gal-9 on collagen-induced arthritis
      (CIA) in a mouse model were also elucidated. RESULTS: The percentage of Gal-9
      positive cells in ST samples and the amount of Gal-9 in synovial fluid samples
      were significantly higher in patients with RA than in patients with OA,
      suggesting the involvement of Gal-9 in the development of RA. Compared with the 2
      wild-type Gal-9 forms, stable Gal-9, a mutant protein resistant to proteolysis,
      significantly induced apoptosis of FLS from RA patients. In contrast, other
      galectins, such as Gal-1, Gal-3, and Gal-8, did not induce apoptosis or suppress
      the proliferation of human RA FLS. Stable Gal-9 preferentially induced apoptosis
      and suppressed the proliferation of RA FLS in vitro. It also induced apoptosis of
      cells in RA ST implanted into SCID mice in vivo. In a mouse model of CIA,
      apoptotic cells were detected in the joints of stable Gal-9-treated mice, but not
      phosphate buffered saline-treated mice, and suppressed CIA characterized by
      pannus formation with inflammatory cell infiltration and bone/cartilage
      destruction. CONCLUSION: Gal-9-induced apoptosis of hyperproliferative RA FLS may
      play a critical role in the suppression of RA.

PMID- 18050193
TI  - Determination of N-glycosylation sites and site heterogeneity in a monoclonal
      antibody by electrospray quadrupole ion-mobility time-of-flight mass
      spectrometry.
AB  - This paper presents an improved analytical method for glycosylation structural
      characterizations of a monoclonal antibody (mAb) using a newly developed
      quadrupole ion-mobility time-of-flight (ESI-Q-IM-TOF) mass spectrometer. Using
      this method, high-resolution mass spectra were acquired to produce the overall
      glycosylation profile of the mAb. Additionally, the light and heavy chains from
      the reduced antibody were separated in the gas phase by the ion mobility
      functionality of the instrument, allowing accurate mass measurement of each
      subunit. Furthermore, the glycan sequences, as well as the glycosylation site,
      were determined by a two-step sequential fragmentation process using the unique
      dual-collision-cell design of the instrument, thus providing detailed
      characterizations of the glycan structures.

PMID- 18050194
TI  - Analysis of transition-metal acetylacetonate complexes by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Transition-metal acetylacetonate complexes of the form Metal(acac)(2), where
      Metal = Fe(II), Co(II), Ni(II), Cu(II), and Zn(II), and Metal(acac)(3), where
      Metal = V(III), Cr(III), Mn(III), Fe(III), and Co(III), were investigated by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS). The data was acquired using the aprotic, electron transfer matrix,
      2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]malononitrile (DCTB), and
      the observation of positive radical ions is shown clearly to depend on the metal
      element and the oxidation state it occupies. The ionization energy of DCTB was
      calculated to be 8.08 eV by density functional theory methods, which is notably
      lower than the experimental value, but within the range of other computational
      values. This value is very close to those of the analytes, so the existing
      electron transfer mechanism which is based on the ionization energies of the
      matrix and analyte, cannot be used predictively. Similarly, the data neither
      proves nor disproves the validity of the existing electron transfer ionization
      mechanism, with respect to metal coordination complexes without strong
      chromophores. In this case, periodic trends may be more useful in explaining the
      observed species and the prediction of species from sets of similar complexes.
      The addition of a sodium salt benefits the MALDI-TOFMS characterization of
      certain compounds studied, but the benefit of the addition of ammonium or silver
      salts is negligible.

PMID- 18050195
TI  - Rates of infiltration by macrophages and dendritic cells and expression of
      interleukin-18 and interleukin-12 in the chronic inflammatory lesions of
      Sjogren's syndrome: correlation with certain features of immune hyperactivity and
      factors associated with high risk of lymphoma development.
AB  - OBJECTIVE: To evaluate the expression profile of infiltrating macrophages and
      dendritic cells (DCs) as well as of interleukin-18 (IL-18) and IL-12 in the minor
      salivary gland (MSG) lesions of patients with Sjogren's syndrome (SS), and to
      assess the relationship of these factors with disease parameters. METHODS:
      Macrophages, DCs, T cells, B cells, proIL-18, mature IL-18, and IL-12 were
      detected by single- and double-labeling immunohistochemistry in MSG specimens
      from 21 patients with primary SS (13 of 21 tested for IL-12), 7 patients with
      secondary SS, and 9 disease control patients. Expression profiles were assessed
      for correlations with various disease parameters, including adverse predictors of
      lymphoma development. RESULTS: MSGs from patients with SS (but not from disease
      controls) manifested increased infiltration by macrophages and DCs, strong
      expression of IL-18 by macrophages (particularly in B cell-rich areas and in
      germinal center-like structures in primary SS), and expression of IL-12 by
      mononuclear cell infiltrates. In primary SS, high infiltration by macrophages
      correlated with SG enlargement (P = 0.01). The DC infiltration rate correlated
      positively with the macrophage infiltration rate (P = 0.04), occurrence of SG
      enlargement (P = 0.03), and presence of C4 hypocomplementemia (P = 0.05), and
      inversely with serum C4 complement levels (P = 0.001). The rate of infiltration
      by IL-18-expressing cells correlated positively with biopsy focus scores (P <
      0.001), larger infiltrates of macrophages (P = 0.01), DCs (P = 0.01), and B cells
      (P = 0.02), and SG enlargement (P = 0.02), and negatively with serum C4
      complement levels (P = 0.02). The rate of infiltration by IL-12-expressing cells
      correlated inversely with that by IL-18-expressing cells (P = 0.001), biopsy
      focus scores (P = 0.003), and SG enlargement (P = 0.01), and positively with
      serum C4 complement levels (P = 0.05). CONCLUSION: In patients with primary SS,
      infiltration of the SG by macrophages and DCs and expression of IL-18 and IL-12
      appear to play active roles in the expansion and organization of infiltrative
      injuries and have a correlation with certain predictors of lymphoma development.

PMID- 18050197
TI  - Association of an IRF5 gene functional polymorphism with Sjogren's syndrome.
AB  - OBJECTIVE: Interferon regulatory factor 5 (IRF-5) is a transcription factor
      involved in the regulation of the host defense. Previous studies have
      demonstrated a significant association of various IRF5 gene polymorphisms with
      systemic lupus erythematosus (SLE) in Caucasians. The purpose of this case
      control study was to investigate whether IRF5 polymorphisms are involved in the
      genetic predisposition to primary Sjogren's syndrome (SS), an autoimmune disease
      closely related to SLE. METHODS: We analyzed IRF5 rs2004640, rs2070197,
      rs10954213, and rs2280714 polymorphisms in a cohort of 212 primary SS patients
      and 162 healthy blood donors, all of whom were of Caucasian origin. The 4
      polymorphisms examined were genotyped by competitive allele-specific polymerase
      chain reaction using fluorescence resonance energy transfer technology. RESULTS:
      The IRF5 rs2004640 GT or TT genotype (T allele carriers) was identified in 87% of
      primary SS patients compared with 77% of controls (P = 0.01, odds ratio [OR] 1.93
      [95% confidence interval (95% CI) 1.15-3.42]). The IRF5 rs2004640 T allele was
      found on 59% of chromosomes from primary SS patients compared with 52% of
      chromosomes from controls (P = 0.04, OR 1.36 [95% CI 1.01-1.83]). No significant
      association of primary SS with rs2070197, rs10954213, or rs2280714 was seen when
      they were analyzed independently. Nevertheless, haplotype reconstructions based
      on the 4 polymorphisms examined suggest that various allele combinations of
      rs2004640 and rs2070197 could define susceptibility or protective haplotypes.
      CONCLUSION: This study is the first to demonstrate a significant association
      between primary SS and the IRF5 rs2004640 T allele. These results, which require
      further replication on larger populations, suggest that besides their association
      with identical major histocompatibility complex gene polymorphisms, primary SS
      and SLE share IRF gene polymorphisms as a common genetic susceptibility factor.

PMID- 18050196
TI  - Augmented interferon-alpha pathway activation in patients with Sjogren's syndrome
      treated with etanercept.
AB  - OBJECTIVE: Recent clinical trials suggest that etanercept is ineffective in
      controlling Sjogren's syndrome (SS). To address the hypothesis that tumor
      necrosis factor blockade can result in increased levels of interferon-alpha
      (IFNalpha) and BAFF, we quantified those mediators in plasma from etanercept- and
      placebo-treated SS patients. METHODS: We studied plasma samples from 20 patients
      with SS treated with etanercept (25 mg twice weekly) or placebo in a 12-week,
      randomized, double-blind clinical trial. In addition, we studied plasma samples
      from 29 healthy controls. IFNalpha activity was determined by reporter cell
      assay, and BAFF levels were determined by enzyme-linked immunosorbent assay.
      RESULTS: Baseline IFNalpha plasma activity and BAFF levels were increased in SS
      patients compared with healthy controls (mean +/- SD IFNalpha plasma activity
      score 4.43 +/- 2.60 versus 2.08 +/- 0.91; P < 0.0001) (mean +/- SD BAFF level
      0.83 +/- 0.27 ng/ml versus 0.60 +/- 0.15 ng/ml; P = 0.008). A significant
      increase in IFNalpha activity was detected after 12 weeks of treatment in the
      etanercept group, but not in the placebo group (P = 0.04 and P = 0.58,
      respectively). Furthermore, a statistically significant increase in BAFF levels
      was noted in patients receiving etanercept, but not in those receiving placebo (P
      = 0.01 and P = 0.56, respectively). In vitro culture of control peripheral blood
      mononuclear cells with etanercept resulted in a dose-dependent increase in the
      expression of IFNalpha and the IFNalpha-inducible genes IFN-induced protein with
      tetratricopeptide repeats 1 and BAFF. CONCLUSION: IFNalpha activity and BAFF
      levels are elevated in the plasma of patients with SS compared with healthy
      controls. Etanercept treatment exacerbates IFNalpha and BAFF overexpression,
      providing a possible explanation for the lack of efficacy of this agent in SS.

PMID- 18050198
TI  - Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in
      patients with ankylosing spondylitis: a multicenter, randomized, double-blind,
      placebo-controlled study.
AB  - OBJECTIVE: To compare the efficacy of adalimumab versus placebo in reducing
      spinal and sacroiliac (SI) joint inflammation, by magnetic resonance imaging
      (MRI) in patients with active ankylosing spondylitis (AS). METHODS: This was a
      randomized, multicenter, double-blind, placebo-controlled study. Patients (n =
      82) received 40 mg adalimumab or placebo every other week during an initial 24
      week double-blind period. MRIs of both the spine and SI joints were obtained at
      baseline, week 12, and week 52. Spinal and SI joint inflammation were measured
      using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index.
      RESULTS: The spine SPARCC score in placebo-treated patients increased by a mean
      of 9.4% from baseline, compared with a mean decrease of 53.6% in adalimumab
      treated patients (P < 0.001); the SI joint SPARCC score decreased by a mean of
      12.7% from baseline in placebo-treated patients and by 52.9% in adalimumab
      treated patients (P = 0.017). The response in adalimumab-treated patients was
      maintained at week 52. Placebo-treated patients were switched to open-label
      adalimumab treatment at week 24 and experienced similar reductions in spinal and
      SI joint inflammation by week 52. Similar large reductions in the spine and SI
      joint SPARCC scores were noted, even in patients who failed to meet the
      ASsessment in Ankylosing Spondylitis (International Working Group) criteria
      (nonresponders) at 12 weeks. In adalimumab-treated patients, a reduced C-reactive
      protein concentration at week 12 was significantly associated with improvement in
      the spine SPARCC score (P = 0.018). CONCLUSION: Adalimumab significantly reduced
      both spinal and SI joint inflammation in patients with active AS after 12 weeks
      of treatment, and these improvements were maintained for up to 52 weeks.

PMID- 18050199
TI  - Longitudinal assessment of synovial, lymph node, and bone volumes in inflammatory
      arthritis in mice by in vivo magnetic resonance imaging and microfocal computed
      tomography.
AB  - OBJECTIVE: To develop longitudinal 3-dimensional (3-D) measures of outcomes of
      inflammation and bone erosion in murine arthritis using contrast-enhanced
      magnetic resonance imaging (CE-MRI) and in vivo microfocal computed tomography
      (micro-CT) and, in a pilot study, to determine the value of entry criteria based
      on age versus synovial volume in therapeutic intervention studies. METHODS: CE
      MRI and in vivo micro-CT were performed on tumor necrosis factor-transgenic (TNF
      Tg) mice and their wild-type littermates to quantify the synovial and popliteal
      lymph node volumes and the patella and talus bone volumes, respectively, which
      were validated histologically. These longitudinal outcome measures were used to
      assess the natural history of erosive inflammatory arthritis. We also performed
      anti-TNF versus placebo efficacy studies in TNF-Tg mice in which treatment was
      initiated according to either age (4-5 months) or synovial volume (3 mm(3) as
      detected by CE-MRI). Linear regression was performed to analyze the correlation
      between synovitis and focal erosion. RESULTS: CE-MRI demonstrated the highly
      variable nature of TNF-induced joint inflammation. Initiation of treatment by
      synovial volume produced significantly larger treatment effects on the synovial
      volume (P = 0.04) and the lymph node volume (P < 0.01) than did initiation by
      age. By correlating the MRI and micro-CT data, we were able to demonstrate a
      significant relationship between changes in synovial and patellar volumes (R(2) =
      0.75, P < 0.01). CONCLUSION: In vivo CE-MRI and micro-CT 3-D outcome measures are
      powerful tools that accurately demonstrate the progression of erosive
      inflammatory arthritis in mice. These methods can be used to identify mice with
      arthritis of similar severity before intervention studies are initiated, thus
      minimizing heterogeneity in outcome studies of chronic arthritis seen between
      genetically identical littermates.

PMID- 18050200
TI  - Can biochemical markers serve as surrogates for imaging in knee osteoarthritis?
AB  - OBJECTIVE: Osteoarthritis (OA) is a complex heterogeneous joint disease affecting
      more than 35 million people worldwide. The current gold standard diagnostic
      investigation is the plain radiograph, which lacks sensitivity. Biochemical
      markers have the potential to act as adjunct markers for imaging in the
      assessment of knee OA. We undertook this study to determine the association
      between individual biochemical markers and radiographic features, and to
      establish whether the association is strengthened when selected biochemical
      markers are combined into a single factor (a theoretical marker). METHODS: Twenty
      serum and urinary biochemical markers were analyzed in 119 patients with
      predominantly tibiofemoral knee OA. Pearson's correlation was performed, and
      corresponding coefficients of determination (R(2)) were calculated to determine
      the association between biochemical markers and a range of imaging features from
      radiographs and dual x-ray absorptiometry of the knee. Biochemical markers
      demonstrating a significant association (P < 0.05) with a specific imaging
      feature were combined by principal components analysis (PCA). Pearson's
      correlation was repeated to establish whether the combined panel of biochemical
      markers showed a stronger association with imaging than the best single marker.
      RESULTS: Fourteen biochemical markers showed significant associations with one or
      more imaging features. By combining specific panels of biochemical markers to
      form factors, the association of markers with imaging features (R(2)) increased
      from 11.9% to 22.7% for the Kellgren/Lawrence (K/L) score, from 5.9% to 9.2% for
      joint space width (JSW), from 6.6% to 10.8% for sclerosis, from 13.5% to 22.6%
      for osteophytes, and from 12.0% to 14.2% for bone mineral density (BMD).
      Biochemical markers identifying patients with osteophytes overlapped with those
      correlated with a high K/L score, while markers of subchondral BMD formed a
      completely separate group. Biochemical markers of JSW included markers associated
      with both osteophytes and BMD. CONCLUSION: The PCA results suggest that
      biochemical marker combinations may be more sensitive than individual biochemical
      markers for reflecting structural damage in patients with knee OA. The
      differences in biochemical marker profiles associated with osteophytes compared
      with those associated with subchondral BMD raise the possibility that these 2
      processes, commonly seen in bone in knee OA, have underlying biologic
      differences.

PMID- 18050201
TI  - Effect of meniscal damage on the development of frequent knee pain, aching, or
      stiffness.
AB  - OBJECTIVE: To evaluate the effect of meniscal damage on the development of
      frequent knee pain, aching, or stiffness in middle-aged and older adults.
      METHODS: The Multicenter Osteoarthritis Study is a prospective study of 3,026
      individuals 50 years of age or older who have or are at high risk of developing
      knee osteoarthritis (OA). We investigated knees at baseline and at 15 months.
      Case knees (n = 110) were those with no pain, aching, or stiffness on most days
      at baseline, but that had developed frequent pain, aching, or stiffness at 15
      months. Control knees (n = 220) were drawn randomly from knees with no frequent
      symptoms at baseline that did not become case knees. Using 1.0T magnetic
      resonance imaging performed at baseline and at followup, 2 musculoskeletal
      radiologists blinded to the case-control status assessed the meniscal damage
      using the following scale: 0 = intact, 1 = minor tear, 2 = nondisplaced tear or
      prior surgical repair, and 3 = displaced tear, resection, maceration, or
      destruction. The effect of meniscal damage was analyzed by contingency tables and
      logistic regression. RESULTS: Meniscal damage was common at baseline both in case
      knees (38%) and in control knees (29%). Although there was a modest association
      between the meniscal damage score (range 0-3) and the development of frequent
      knee pain, aching, or stiffness (odds ratio [OR] 1.21, 95% confidence interval
      [95% CI] 0.96-1.51, adjusted for age, sex, and body mass index), meniscal damage
      was mostly present in knees with OA. When considering the co-occurrence of OA, we
      found no independent association between meniscal damage and the development of
      frequent knee symptoms (OR 1.05, 95% CI 0.80-1.37). CONCLUSION: In middle-aged
      and older adults, any association between meniscal damage and the development of
      frequent knee pain seems to be present because both pain and meniscal damage are
      related to OA and not because of a direct link between the two.

PMID- 18050202
TI  - The efficacy and safety of diacerein in the treatment of painful osteoarthritis
      of the knee: a randomized, multicenter, double-blind, placebo-controlled study
      with primary end points at two months after the end of a three-month treatment
      period.
AB  - OBJECTIVE: To determine whether the efficacy of diacerein persists at 2 months
      after the end of a 3-month treatment period, compared with placebo, in patients
      with painful knee osteoarthritis (OA). METHODS: After a 1-week nonsteroidal
      antiinflammatory drug washout period, patients received either diacerein or
      placebo for 3 months, followed by an off-treatment period of 3 months to
      determine the carryover effects of the drug. Although patients were followed up
      through month 6, the primary efficacy end point was the percent change from
      baseline in pain (Western Ontario and McMaster Universities Osteoarthritis Index
      [WOMAC] A) at month 5 (i.e., 2 months after the end of treatment) compared with
      placebo. The co-primary efficacy end point was the percent change from baseline
      in the total WOMAC score, also at month 5 versus placebo. RESULTS: Two hundred
      three patients were screened, and 168 patients with painful knee OA were
      randomized. One hundred sixty-five patients were analyzed in an intent-to-treat
      analysis. At month 5, diacerein showed statistically significant superiority
      versus placebo as assessed with both the WOMAC A (P < 0.0001) and the total WOMAC
      (P < 0.0001), demonstrating the carryover effect of the drug. This superiority
      was already evident from month 2 for pain (P = 0.001) and month 1 for total WOMAC
      (P = 0.0021). Diacerein was safe and well tolerated. No serious or previously
      undocumented adverse events were observed during the study. CONCLUSION: This is
      the first published study of a symptomatic slow-acting OA drug in which the time
      of assessment of the primary outcome end points was 2 months after the end of a 3
      month treatment period. The results show that diacerein is safe and effective for
      the treatment of knee OA and has a long carryover effect.

PMID- 18050203
TI  - Articular cartilage and biomechanical properties of the long bones in Frzb
      knockout mice.
AB  - OBJECTIVE: Ligands and antagonists of the WNT pathway are linked to osteoporosis
      and osteoarthritis. In particular, polymorphisms in the FRZB gene, a secreted WNT
      antagonist, have been associated with osteoarthritis. The aim of this study was
      to examine cartilage and bone in Frzb(-/-) mice. METHODS: The Frzb gene in mice
      was inactivated using a Cre/loxP strategy. Three models of osteoarthritis were
      used: collagenase, papain, and methylated bovine serum albumin induced. Bone
      biology was studied using density measurements and microfocal computed
      tomography. Bone stiffness and mechanical loading-induced bone adaptation were
      studied by compression of the ulnae. RESULTS: Targeted deletion of the Frzb gene
      in mice increased articular cartilage loss during arthritis triggered by
      instability, enzymatic injury, or inflammation. Cartilage damage in Frzb(-/-)
      mice was associated with increased WNT signaling and matrix metalloproteinase 3
      (MMP-3) expression and activity. Frzb(-/-) mice had increased cortical bone
      thickness and density, resulting in stiffer bones, as demonstrated by stress
      strain relationship analyses. Moreover, Frzb(-/-) mice had an increased
      periosteal anabolic response to mechanical loading as compared with wild-type
      mice. CONCLUSION: The genetic association between osteoarthritis and FRZB
      polymorphisms is corroborated by increased cartilage proteoglycan loss in 3
      different models of arthritis in Frzb(-/-) mice. Loss of Frzb may contribute to
      cartilage damage by increasing the expression and activity of MMPs, in a WNT
      dependent and WNT-independent manner. FRZB deficiency also resulted in thicker
      cortical bone, with increased stiffness and higher cortical appositional bone
      formation after loading. This may contribute to the development of osteoarthritis
      by producing increased strain on the articular cartilage during normal locomotion
      but may protect against osteoporotic fractures.

PMID- 18050204
TI  - Role of hypoxia and cAMP in the transdifferentiation of human fetal cardiac
      fibroblasts: implications for progression to scarring in autoimmune-associated
      congenital heart block.
AB  - OBJECTIVE: Identification of isolated congenital heart block (CHB) predicts, with
      near certainty, the presence of maternal anti-SSA/Ro antibodies; however, the 2%
      incidence of CHB in first offspring of anti-SSA/Ro+ mothers, 20% recurrence in
      subsequent pregnancies, and discordance in identical twins suggest that an
      environmental factor amplifies the effect of the antibody. Accordingly, this
      study was carried out to explore the hypothesis that hypoxia potentiates a
      profibrosing phenotype of the fetal cardiac fibroblast. METHODS: Evidence of an
      effect of hypoxia was sought by immunohistologic evaluation of CHB-affected fetal
      heart tissue and by determination of erythropoietin levels in cord blood. The in
      vitro effect of hypoxia on gene expression and phenotype in fibroblasts derived
      from fetal hearts and lungs was investigated by Affymetrix arrays, quantitative
      polymerase chain reaction (PCR), immunofluorescence, and immunoblotting. RESULTS:
      In vivo hypoxic exposure was supported by the prominent intracellular fibroblast
      expression of hypoxia-inducible factor 1alpha in conduction tissue from 2 fetuses
      in whom CHB led to death. The possibility that hypoxia was sustained was
      suggested by significantly elevated erythropoietin levels in cord blood from CHB
      affected, as compared with unaffected, anti-SSA/Ro-exposed neonates. In vitro
      exposure of cardiac fibroblasts to hypoxia resulted in transdifferentiation to
      myofibroblasts (a scarring phenotype), as demonstrated on immunoblots and
      immunofluorescence by increased expression of smooth muscle actin (SMA), an
      effect not seen in lung fibroblasts. Hypoxia-exposed cardiac fibroblasts
      expressed adrenomedullin at 4-fold increased levels, as determined by Affymetrix
      array, quantitative PCR, and immunofluorescence, thus focusing attention on cAMP
      as a modulator of fibrosis. MDL12,330A, an adenylate cyclase inhibitor that
      lowers the levels of cAMP, increased expression of fibrosis-related proteins
      (mammalian target of rapamycin, SMA, plasminogen activator inhibitor type 1, and
      type I collagen), while the cAMP activator forskolin attenuated transforming
      growth factor beta-elicited fibrosing end points in the cardiac fibroblasts.
      CONCLUSION: These findings provide evidence that hypoxia may amplify the
      injurious effects of anti-SSA/Ro antibodies. Modulation of cAMP may be a key
      component in the scarring phenotype. Further assessment of the susceptibility of
      cardiac fibroblasts to cAMP modulation offers a new research direction in CHB.

PMID- 18050205
TI  - Hyperexpression of cyclooxygenase 2 in the lupus immune system and effect of
      cyclooxygenase 2 inhibitor diet therapy in a murine model of systemic lupus
      erythematosus.
AB  - OBJECTIVE: To investigate the role of cyclooxygenase 2 (COX-2) in the functioning
      of different cell types involved in the lupus autoimmune response, and to examine
      the therapeutic effect of COX-2 inhibitors in mice prone to spontaneously develop
      systemic lupus erythematosus (SLE). METHODS: Lupus-prone (SWR x NZB)F(1) mice
      were fed with a diet containing different doses of the COX-2-specific inhibitor
      celecoxib or the nonspecific inhibitor aspirin, or a combination of both, and the
      effects of the therapy on autoantibody production, development of lupus
      nephritis, and mortality were determined. Expression of COX-2 by different cells
      of the lupus immune system and the effect of COX-2 inhibitors on the function of
      these cells in vitro and in vivo were assessed. RESULTS: The immune cells of mice
      with SLE spontaneously hyperexpressed COX-2, and COX-2 inhibitors could cause
      cell apoptosis. Treatment with COX-2 inhibitors resulted in decreased
      autoantibody production and inhibition of the T cell response to the major lupus
      autoantigen, nucleosome, and its presentation by antigen-presenting cells.
      Surprisingly, a significant increase in survival occurred only in mice receiving
      intermittent therapy with the lowest dose of celecoxib (500 parts per million),
      approximating <100 mg of celecoxib/day in humans. A continuous diet, but not
      intermittent feeding, with the combination of celecoxib and aspirin delayed
      development of nephritis temporarily, but failed to prolong survival. Indeed,
      treatment with aspirin alone increased mortality. CONCLUSION: The contributions
      of the major players in the pathogenic autoimmune response, namely, T cells, B
      cells, dendritic cells, and macrophages that are abnormally hyperactive in lupus,
      depend on the increased expression and activity of COX-2, similar to inflammatory
      cells in target organs. Intermittent pulse therapy with low doses of select COX-2
      inhibitors would be of value in the treatment of lupus.

PMID- 18050206
TI  - Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in
      patients with systemic lupus erythematosus: results of a multicenter, phase Ib,
      double-blind, placebo-controlled, dose-escalating trial.
AB  - OBJECTIVE: To assess the safety and tolerability of atacicept in patients with
      systemic lupus erythematosus (SLE) and the biologic effect of atacicept on B
      lymphocyte and immunoglobulin levels. Atacicept is a TACI-Ig fusion protein that
      inhibits B cell stimulation by binding to B lymphocyte stimulator and a
      proliferation-inducing ligand. METHODS: This phase Ib, double-blind, placebo
      controlled, dose-escalating trial comprised 6 cohorts of patients treated with
      atacicept or placebo in a 3:1 ratio of active drug to placebo (n = 8 per group; n
      = 7 in cohort 5). Cohorts 1-4 received a single subcutaneous dose of placebo or
      either 0.3 mg/kg, 1 mg/kg, 3 mg/kg, or 9 mg/kg of atacicept. Cohorts 5 and 6
      received weekly doses of placebo or either 1 mg/kg or 3 mg/kg of atacicept for 4
      weeks. Patients were followed up for 6 weeks (cohorts 1-4) or 9 weeks (cohorts 5
      and 6). Patients with mild-to-moderate SLE were enrolled. RESULTS: Biologic
      activity of atacicept was demonstrated by dose-dependent reductions in
      immunoglobulin levels and in mature and total B cell numbers. This effect was
      most pronounced in the repeated-dose cohorts and was sustained throughout the
      followup period. There were no changes in the numbers of T cells, natural killer
      cells, or monocytes. Mild injection-site reactions occurred more frequently among
      the atacicept group than the placebo group. There were no differences in the
      frequency or type of adverse events and no severe or serious adverse events in
      patients treated with atacicept. CONCLUSION: Atacicept administered
      subcutaneously was well tolerated and demonstrated biologic activity consistent
      with the proposed mechanism of action.

PMID- 18050208
TI  - Disease remission and sustained halting of radiographic progression with
      combination etanercept and methotrexate in patients with rheumatoid arthritis.
AB  - OBJECTIVE: The Trial of Etanercept and Methotrexate with Radiographic Patient
      Outcomes (TEMPO) is a 3-year, double-blind, multicenter study evaluating the
      efficacy and safety of etanercept, methotrexate, and the combination of
      etanercept plus methotrexate in patients with active rheumatoid arthritis (RA).
      The results after 1 and 2 years of the study have been previously reported. Here
      we provide the 3-year clinical and radiographic outcomes and safety of
      etanercept, methotrexate, and the combination in patients with RA. METHODS: In
      this randomized, double-blind, multicenter TEMPO study, 682 patients received
      etanercept 25 mg twice weekly, methotrexate < or =20 mg weekly, or the
      combination. Key efficacy assessments included the Disease Activity Score (DAS)
      and the DAS in 28 joints. RESULTS: Combination therapy resulted in significantly
      greater improvement in the DAS and in more patients with disease in remission
      than either monotherapy. This finding was confirmed by longitudinal analysis;
      patients receiving combination therapy were more than twice as likely to have
      disease in remission than those receiving either monotherapy. Independent
      predictors of remission included male sex, lower disease activity, lower level of
      joint destruction, and/or better physical function. Combination and etanercept
      therapy both resulted in significantly less radiographic progression than did
      methotrexate (P < 0.05). Etanercept and combination treatment were well
      tolerated, with no new safety findings. CONCLUSION: Etanercept plus methotrexate
      showed sustained efficacy through 3 years and remained more effective than either
      monotherapy, even after adjustment for patient withdrawal. Combination therapy
      for 3 years led to disease remission and inhibition of radiographic progression,
      2 key goals for treatment of patients with RA.

PMID- 18050209
TI  - Fine specificity of the anti-citrullinated protein antibody response is
      influenced by the shared epitope alleles.
AB  - OBJECTIVE: In classic studies on the genetic background of antibody production,
      the major histocompatibility complex (MHC) has been shown to act as the most
      prominent immune response gene that controls the magnitude and the specificity of
      antibody production. The strongest genetic risk factor for rheumatoid arthritis
      (RA), the human MHC HLA-DRB1 shared epitope (SE) alleles, predisposes for
      antibodies against citrullinated proteins (ACPAs). ACPA levels are higher in SE
      positive patients with RA than in SE-negative patients with RA. The aim of the
      present study was to determine whether SE influences not only the magnitude but
      also the specificity of the ACPA response. METHODS: In 2 cohorts of anti
      citrullinated peptide 2-positive patients with RA, one from a study of recent
      onset arthritis (n = 206) and the other from a treatment strategy study (n =
      141), serum antibodies against a citrullinated peptide derived from vimentin
      (cVim) and antibodies against a citrullinated fibrinogen peptide (cFibr) were
      determined by enzyme-linked immunosorbent assay. HLA-DRB1 genotyping was
      performed. RESULTS: In the first cohort, SE alleles were significantly associated
      with the presence of antibodies against cVim (odds ratio [OR] 4.95, 95%
      confidence interval [95% CI] 1.87-15.3) and were not significantly associated
      with the presence of antibodies against cFibr (OR 1.71, 95% CI 0.70-4.14). These
      results were replicated in the second cohort (OR 5.05, 95% CI 1.92-13.6 and OR
      1.19, 95% CI 0.30-3.97, respectively). CONCLUSION: In 2 cohorts of ACPA-positive
      patients with RA, SE alleles predisposed for the development of antibodies
      against cVim but not for the development of antibodies against cFibr. These data
      indicate that SE alleles act as "classic" immune response genes in the ACPA
      response, because they influence both the magnitude and the specificity of this
      RA-specific antibody response.

PMID- 18050210
TI  - HO-1 promoter polymorphism associated with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the role of the HO-1 gene as a novel functional
      candidate gene for rheumatoid arthritis (RA). METHODS: We performed a case
      control study including 736 RA patients and 846 healthy controls of Spanish
      Caucasian origin. Two putative functional HO-1 promoter polymorphisms, a (GT)(n)
      microsatellite and a -413 A/T single-nucleotide polymorphism (SNP), were selected
      as genetic markers and genotyped using polymerase chain reaction-based methods.
      In addition, the intracellular expression of heme oxygenase 1 (HO-1) was
      determined in healthy individuals with different (GT)(n) genotypes. RESULTS: The
      distribution of HO-1 (GT)(n) short (S) alleles (< or =25 GT repeats) and long (L)
      alleles (>25 GT repeats) revealed a significant protective effect of S (GT)(n)
      alleles (P = 0.019) (odds ratio [OR] 0.8, 95% confidence interval [95% CI] 0.7
      0.9) and the SS (GT)(n) genotype (P = 0.002) (OR 0.6, 95% CI 0.4-0.9). In
      contrast, the -413 HO-1 promoter SNP did not yield any statistically significant
      deviation between RA patients and controls, considering either allele or genotype
      frequencies. The haplotype analysis showed a strong protective effect of the S/A
      haplotype (P = 7 x 10(-7), corrected P [P(corr)] = 3 x 10(-6)) (OR 0.4, 95% CI
      0.3-0.6), whereas the L/A haplotype showed the opposite tendency (P = 0.008,
      P(corr) = 0.03) (OR 1.2, 95% CI 1.0-1.4). In addition, we demonstrated that
      monocytes from individuals carrying the SS (GT)(n) genotype showed a
      significantly higher percentage of HO-1 expression than did cells from LL
      homozygous individuals (P = 0.0003). CONCLUSION: In this study, we identified the
      HO-1 (GT)(n) microsatellite as a new genetic marker involved in RA genetics in
      our population.

PMID- 18050211
TI  - Treg cells suppress osteoclast formation: a new link between the immune system
      and bone.
AB  - OBJECTIVE: To investigate whether Treg cells can suppress osteoclast
      differentiation, and to define a new potential link between the immune system and
      the skeleton. METHODS: Regulatory CD4+,CD25+,Foxp3+ T cells were isolated and
      purified from the spleen and cocultured with CD11b+ osteoclast precursor cells
      isolated from bone marrow. Osteoclastogenesis and bone erosion were assessed by
      tartrate-resistant acid phosphatase staining and pit resorption assay,
      respectively. In addition, Transwell experiments and cytokine-blocking
      experiments were performed to define the mechanisms of interaction between Treg
      cells and osteoclasts. RESULTS: CD4+,CD25+,Foxp3+ T cells, but not CD4+,CD25- T
      cells, dose dependently inhibited macrophage colony-stimulating factor- and RANKL
      dependent osteoclast formation. Pit formation was inhibited by up to 80% when
      Treg cells were added. The blockade of osteoclast formation was not based on the
      alteration of RANKL/osteoprotegerin balance but was essentially dependent on
      direct cell-cell contact via CTLA-4. Treg cell-mediated expression of
      transforming growth factor beta, interleukin-4 (IL-4), and IL-10 contributed but
      was not essential to the inhibitory effect on osteoclastogenesis. CONCLUSION:
      These data show that CD4+,CD25+,Foxp3+ Treg cells suppress osteoclast formation,
      provide a new link between the immune system and bone, and extend our knowledge
      on regulation of bone homeostasis by the immune system.

PMID- 18050212
TI  - FRZB: a bone and joint connection.

PMID- 18050213
TI  - British Isles Lupus Assessment Group 2004 index is valid for assessment of
      disease activity in systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the construct and criterion validity of the British Isles
      Lupus Assessment Group 2004 (BILAG-2004) index for assessing disease activity in
      systemic lupus erythematosus (SLE). METHODS: Patients with SLE were recruited
      into a multicenter cross-sectional study. Data on SLE disease activity (scores on
      the BILAG-2004 index, Classic BILAG index, and Systemic Lupus Erythematosus
      Disease Activity Index 2000 [SLEDAI-2K]), investigations, and therapy were
      collected. Overall BILAG-2004 and overall Classic BILAG scores were determined by
      the highest score achieved in any of the individual systems in the respective
      index. Erythrocyte sedimentation rates (ESRs), C3 levels, C4 levels, anti-double
      stranded DNA (anti-dsDNA) levels, and SLEDAI-2K scores were used in the analysis
      of construct validity, and increase in therapy was used as the criterion for
      active disease in the analysis of criterion validity. Statistical analyses were
      performed using ordinal logistic regression for construct validity and logistic
      regression for criterion validity. Sensitivity, specificity, positive predictive
      value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Of the
      369 patients with SLE, 92.7% were women, 59.9% were white, 18.4% were Afro
      Caribbean and 18.4% were South Asian. Their mean +/- SD age was 41.6 +/- 13.2
      years and mean disease duration was 8.8 +/- 7.7 years. More than 1 assessment was
      obtained on 88.6% of the patients, and a total of 1,510 assessments were
      obtained. Increasing overall scores on the BILAG-2004 index were associated with
      increasing ESRs, decreasing C3 levels, decreasing C4 levels, elevated anti-dsDNA
      levels, and increasing SLEDAI-2K scores (all P < 0.01). Increase in therapy was
      observed more frequently in patients with overall BILAG-2004 scores reflecting
      higher disease activity. Scores indicating active disease (overall BILAG-2004
      scores of A and B) were significantly associated with increase in therapy (odds
      ratio [OR] 19.3, P < 0.01). The BILAG-2004 and Classic BILAG indices had
      comparable sensitivity, specificity, PPV, and NPV. CONCLUSION: These findings
      show that the BILAG-2004 index has construct and criterion validity.

PMID- 18050214
TI  - Involvement of protein kinase Czeta in interleukin-1beta induction of ADAMTS-4
      and type 2 nitric oxide synthase via NF-kappaB signaling in primary human
      osteoarthritic chondrocytes.
AB  - OBJECTIVE: Protein kinase Czeta (PKCzeta), an atypical PKC, has been found to be
      transcriptionally up-regulated in human osteoarthritic (OA) articular cartilage.
      This study was undertaken to examine the role of PKCzeta in interleukin-1beta (IL
      1beta)-induced NF-kappaB signaling in human OA chondrocytes, and ultimately to
      better understand its function in the regulation of downstream mediators of
      cartilage matrix degradation. METHODS: Pharmacologic inhibitors or genetic
      knockdown techniques were used to investigate the role of PKCzeta. Western blot
      analysis was used to evaluate phosphorylation of PKCzeta and NF-kappaB.
      Quantitative polymerase chain reaction (PCR) and activity assays were used to
      evaluate ADAMTS-4 expression and aggrecanase activity, respectively. Quantitative
      PCR, biochemical identification, and Western blot analysis were used to evaluate
      type 2 nitric oxide synthase (NOS2) and NO production. RESULTS: Phosphorylation
      of PKCzeta and NF-kappaB was induced by IL-1beta treatment in a time-dependent
      manner, and was specifically inhibited by inhibitors of atypical PKCs. Inhibition
      of PKCzeta suppressed IL-1beta-induced up-regulation of ADAMTS-4 messenger RNA
      (mRNA) and aggrecanase activity. Inhibitors of atypical PKCs also inhibited IL
      1beta-induced NO production and NOS2 mRNA expression, demonstrating a novel link
      between PKCzeta and NO production. Furthermore, small interfering RNA- or short
      hairpin RNA-mediated knockdown of PKCzeta mRNA resulted in significant repression
      of both ADAMTS-4 and NOS2 mRNA expression. CONCLUSION: Our results show that
      PKCzeta is involved in the regulation of IL-1beta-induced NF-kappaB signaling in
      human OA chondrocytes, which in turn regulates downstream expression of ADAMTS-4
      and NOS2. Therefore, inhibition of PKCzeta could potentially regulate the
      production of matrix-degrading enzymes as well as NO production and have a
      profound effect on disease progression in OA.

PMID- 18050215
TI  - Hypoxia-inducible factor 1alpha is involved in the prostaglandin metabolism of
      osteoarthritic cartilage through up-regulation of microsomal prostaglandin E
      synthase 1 in articular chondrocytes.
AB  - OBJECTIVE: To investigate crosslinks between catabolic and anabolic pathways in
      articular cartilage by examining the synthesis and distribution pattern of
      microsomal prostaglandin E synthase 1 (mPGES-1) in healthy and osteoarthritic
      (OA) cartilage and analyzing its functional relationship to hypoxia-inducible
      factor 1alpha (HIF-1alpha) in primary articular chondrocytes. METHODS: Normal
      cartilage and OA cartilage were subjected to immunohistochemical staining for
      mPGES-1 and HIF-1alpha. Isolated chondrocytes were cultivated under 21% or 1%
      O(2). Microarray analysis and quantitative reverse transcriptase-polymerase chain
      reaction were used to detect genes differentially expressed in chondrocytes
      cultured under normoxic compared with hypoxic conditions. Immunoblotting was
      conducted to evaluate intracellular protein levels of mPGES and nuclear
      accumulation of HIF-1alpha under different oxygen tension levels and with
      different stimulatory or inhibitory chemical agents. RESULTS: We found enhanced
      levels of expression of the mPGES-1 gene and an increased number of OA
      chondrocytes showing staining for mPGES-1 in OA cartilage. Microarray analysis
      demonstrated that mPGES-1 was among the genes that were up-regulated to the
      greatest degree in primary chondrocytes exposed to 1% O(2). In vitro, hypoxia led
      to an enhanced synthesis of mPGES-1, coinciding with a nuclear accumulation of
      the transcription factor HIF-1alpha. In chondrocyte culture, stimulation with
      dimethyloxaloylglycine promoted the expression of mPGES-1, phosphoglycerate
      kinase 1, and cyclooxygenase 2 (COX-2) by stabilizing HIF-1alpha protein levels.
      A reduction of mPGES-1 synthesis was detected after treatment with 2
      methoxyestradiol, correlating with lower HIF-1alpha activity. In contrast,
      synthesis of mPGES-1 was not influenced by treatment with the specific COX-2
      inhibitor NS398. CONCLUSION: These findings suggest that the transcription factor
      HIF-1alpha is involved in the up-regulation of mPGES-1 and may therefore play an
      important role in the metabolism of OA cartilage.

PMID- 18050216
TI  - Collagen-induced arthritis as a model of hyperalgesia: functional and cellular
      analysis of the analgesic actions of tumor necrosis factor blockade.
AB  - OBJECTIVE: There is a disparity in the animal models used to study pain in
      rheumatoid arthritis (RA), which tends to be acute in nature, and models used to
      assess the pathogenesis of RA. The latter models, like human RA, are lymphocyte
      driven and polyarthritic. We assessed pain behavior and mechanisms in collagen
      induced arthritis (CIA), the model of preclinical arthritis used most commonly in
      the field of immunology. We then validated the model using anti-tumor necrosis
      factor (anti-TNF) therapy, which has analgesic effects in models of inflammation
      as well as in human RA. METHODS: CIA was induced in DBA/1 mice by immunization
      with type II collagen at the base of the tail. Swelling and mechanical and
      thermal hyperalgesia were assessed before and for 28 days after the onset of
      arthritis. Spontaneous behavior was assessed using an automated activity monitor.
      Glial activity was assessed by glial fibrillary acidic protein expression, and
      nerve damage was evaluated by activating transcription factor 3 expression. The
      actions of anti-TNF therapy on nociception were then evaluated. RESULTS:
      Arthritis resulted in a decrease in the threshold for thermal and mechanical
      stimuli, beginning on the day of onset. Decreased spontaneous activity was also
      observed. A significant increase in the number of hyperplasic spinal cord
      astrocytes was observed beginning 10 days after the onset of arthritis. Anti-TNF
      therapy was profoundly analgesic, with an efficacy similar to that of
      cyclooxygenase 2 inhibition, and reduced astrocyte activity in CIA. CONCLUSION:
      This study shows that the CIA model is suitable for testing not only
      antiinflammatory but also analgesic drugs for potential use in RA, and highlights
      the importance of using appropriate disease models to assess relevant pain
      pathways.

PMID- 18050217
TI  - It is the best of times; it is the worst of times: is there a way forward? A
      plethora of treatment options for rheumatoid arthritis, but critical trial design
      issues.

PMID- 18050218
TI  - Resemblance of osteophytes in experimental osteoarthritis to transforming growth
      factor beta-induced osteophytes: limited role of bone morphogenetic protein in
      early osteoarthritic osteophyte formation.
AB  - OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage damage, synovial
      fibrosis, and osteophyte formation. Both transforming growth factor beta
      (TGFbeta) and bone morphogenetic protein 2 (BMP-2) can induce the formation of
      osteophytes during OA, but their specific role in this process is unclear. The
      purpose of this study was to investigate the respective contributions of TGFbeta
      and BMP-2 to OA. METHODS: Mouse knee joints injected with adenovirus (Ad-TGFbeta
      or Ad-BMP-2) were compared histologically with knee joints from murine models of
      OA (joints injected with collagenase and joints from STR/Ort mice with
      spontaneous OA). To further investigate the role of BMP during osteophyte
      formation, adenovirus Ad-Gremlin was injected into knee joints that had
      previously been injected with Ad-TGFbeta or collagenase. RESULTS: BMP-2 induced
      early osteophytes, which bulged from the growth plates on the femur and grew on
      top of the patella, whereas TGFbeta induced early osteophyte formation on the
      bone shaft beneath the collateral ligament on the femur as well as on top of the
      patella. The pattern of osteophyte formation during experimental OA closely
      resembled that of TGFbeta-induced osteophyte formation, but differed from the
      pattern induced by BMP-2. Ad-Gremlin proved to be able to totally block BMP-2
      induced osteophyte formation. However, blocking BMP activity inhibited neither
      TGFbeta-induced nor experimental OA-associated osteophyte formation. CONCLUSION:
      Our findings demonstrate that the role of BMP during the onset of TGFbeta-induced
      and experimental OA-induced osteophyte formation is limited. The latter finding
      does not rule out a role of BMP during osteophyte maturation.

PMID- 18050219
TI  - Antibody responses to Borrelia burgdorferi in patients with antibiotic
      refractory, antibiotic-responsive, or non-antibiotic-treated Lyme arthritis.
AB  - OBJECTIVE: To compare the pattern of antibody responses to Borrelia burgdorferi
      in patients with antibiotic-refractory, antibiotic-responsive, or non-antibiotic
      treated Lyme arthritis as an indirect measure of spirochetal persistence or
      eradication. METHODS: At least 3 serial serum samples from 41 patients with
      antibiotic-refractory arthritis and 23 patients with antibiotic-responsive
      arthritis, and samples from 10 non-antibiotic-treated, historical control
      patients were tested for IgG reactivity with B burgdorferi sonicate and 4
      differentially expressed outer surface lipoproteins of the spirochete, by enzyme
      linked immunosorbent assay. RESULTS: Among non-antibiotic-treated patients,
      antibody titers to B burgdorferi antigens remained high throughout a 2-5-year
      period of arthritis. In contrast, in patients with antibiotic-responsive
      arthritis, in whom joint swelling usually resolved during a 1-month course of
      oral antibiotic therapy, the median antibody titers to most of the spirochetal
      antigens remained steady or decreased during the first 1-3 months after starting
      antibiotic therapy. In patients with antibiotic-refractory arthritis, who had
      persistent joint swelling for a median duration of 10 months despite 2-3 months
      of oral or intravenous antibiotics, the median titers to most antigens increased
      slightly during the first 1-3 months. However, by 4-6 months after starting
      antibiotic therapy, reactivity with all antigens declined similarly in both
      antibiotic-treated groups. CONCLUSION: Whereas the antibody titers to B
      burgdorferi remained high in non-antibiotic-treated patients, the titers declined
      similarly 4-6 months after starting therapy in patients with antibiotic
      responsive or antibiotic-refractory arthritis, suggesting that synovial
      inflammation persisted in patients with antibiotic-refractory arthritis after the
      period of infection.

PMID- 18050220
TI  - Can sciatica induced by disc herniation be treated with tumor necrosis factor
      alpha blockade?

PMID- 18050221
TI  - Safety and efficacy of additional courses of rituximab in patients with active
      rheumatoid arthritis: an open-label extension analysis.
AB  - OBJECTIVE: To determine the safety and efficacy of additional courses of
      rituximab in patients with rheumatoid arthritis (RA). METHODS: An open-label
      extension analysis of RA patients previously treated with rituximab was
      conducted. Patients who had participated in any of 3 double-blind trials were
      eligible for additional courses (2 infusions of 1,000 mg given 2 weeks apart) if
      they exhibited a swollen joint count and tender joint count of > or =8 with > or
      =16 weeks elapsing after the previous course. Safety was assessed in patients
      receiving all or a portion of a rituximab course. Efficacy was assessed 24 weeks
      after each course, using the American College of Rheumatology 20% criteria for
      improvement (ACR20), ACR50, ACR70, European League Against Rheumatism (EULAR)
      response criteria, Disease Activity Score in 28 joints, the disability index of
      the Health Assessment Questionnaire, and Short Form 36 scores, stratified
      according to prior tumor necrosis factor (TNF) inhibitor exposure. RESULTS: A
      total of 1,039 patients received > or =1 course of rituximab. Of these, 570
      received 2 courses, 191 received 3 courses, and 40 received 4 courses, for a
      total of 1,669 patient-years. Irrespective of prior TNF inhibitor exposure, ACR20
      responses were comparable at week 24 after course 1 and at week 24 after course 2
      (65% versus 72%), as were ACR50 and ACR70 responses. EULAR moderate/good
      responses were also comparable in course 2 relative to course 1 (88% versus 79%),
      with EULAR remission occurring in a 2-fold higher proportion of patients after
      course 2 than after course 1 (13% versus 6%). The most common adverse events,
      which were mild-to-moderate acute infusion-related events, decreased with each
      course. The serious infection rate after course 1 (5.1 per 100 patient-years)
      remained stable through additional courses. The proportion of patients with
      circulating IgM and IgG levels below the lower limit of normal (LLN) increased
      with subsequent courses; however, serious infection rates in these patients (5.6
      per 100 patient-years in patients with low IgM levels and 4.8 per 100 patient
      years in patients with low IgG levels were comparable with those in patients with
      immunoglobulin levels above the LLN (4.7 per 100 patient-years). Patients with
      human antichimeric antibody (9.2%) did not exhibit decreasing efficacy or present
      additional safety concerns. CONCLUSION: These findings indicate that patients
      treated with repeated courses of rituximab have sustained clinical responses with
      no new adverse events.

PMID- 18050222
TI  - Immunohistochemical analysis as a means to predict responsiveness to rituximab
      treatment.
AB  - OBJECTIVE: Anti-CD20-mediated B cell depletion with rituximab is a new and
      effective therapy for rheumatoid arthritis (RA). Although B cells in peripheral
      blood (PB) are consistently depleted in all patients, the clinical effects are
      more heterogeneous, possibly related to differences in the depleting effects of
      lymphoid or solid tissues. The aim of this study was to investigate B cell
      depletion in different compartments (PB, bone marrow, and synovium) and determine
      predictive variables for responsiveness to rituximab therapy. METHODS: Before and
      12 weeks after rituximab treatment, samples of PB, bone marrow, and synovium were
      collected from 25 patients with RA refractory to disease-modifying antirheumatic
      drugs and tumor necrosis factor-blocking agents. CD19+ and CD20+ B cells in PB
      and bone marrow were measured by flow cytometric analysis, whereas CD79a+ and
      cytoplasmic CD20+ B cells in the synovium were stained by immunohistochemistry.
      The effects of rituximab on serum Ig and autoantibodies were measured by enzyme
      linked immunosorbent assay. RESULTS: Rituximab effectively depleted the CD20+
      subset of B cells in the PB, bone marrow, and synovium of RA patients. Rituximab
      significantly reduced autoantibody production (anti-citrullinated protein
      antibodies [ACPAs] and rheumatoid factor [RF]), in part due to a nonspecific
      decrease in total Ig production. Importantly, positivity for circulating ACPA
      IgM, in combination with a high infiltration of CD79a+ B cells in the synovium,
      but not of CD138+ plasma cells, was a predictor of clinical outcome after
      rituximab treatment. ACPA IgM titers were independently associated with synovial
      infiltration of CD20-,CD79a+ B cells, but not with CD138+ plasma cells.
      CONCLUSION: These data provide novel insights into the mechanisms of CD20
      mediated B cell depletion in the lymphoid and solid tissues of RA patients and
      suggest a pivotal role for ACPA IgM-producing plasmablasts in RA.

PMID- 18050223
TI  - Articulating a justice ethic for rheumatology: A critical analysis of disparities
      in rheumatic diseases.

PMID- 18050224
TI  - Warfarin and the antiphospholipid syndrome: does one size fit all?

PMID- 18050225
TI  - Measurement of fatigue in systemic lupus erythematosus: a systematic review.
AB  - OBJECTIVE: To systematically review fatigue instruments used in patients with
      systemic lupus erythematosus (SLE) and to seek consensus on which instruments
      should be recommended for future studies and which data on comorbid conditions
      should be reported when evaluating fatigue in patients with SLE. METHODS: We used
      data from Medline and EMBase databases (from January 1970 to June 2006), clinical
      experts, and bibliographies. Data were extracted independently by 4 authors and
      reviewed by a working group and larger expert panel to produce a recommendation.
      Instruments were examined for construct validity, reliability, and responsiveness
      to change. Correlations between fatigue and some components of the Medical
      Outcomes Study Short Form 36 (SF-36), disease activity, and comorbidities were
      reviewed. RESULTS: We identified 34 studies that used 15 fatigue instruments in
      patients with SLE. The Fatigue Severity Scale (FSS) was used in 56% of the
      studies. The Systemic Lupus Activity Measure was significantly correlated with
      fatigue, but the Systemic Lupus Erythematosus Disease Activity Index was not.
      Fatigue was also correlated with pain, poor quality of sleep, depression, and
      with each subscale of the SF-36. CONCLUSION: The working group and expert panel
      recommend the 9-item FSS for evaluating fatigue in SLE patients. Responsiveness
      to change of fatigue instruments has not been well established in SLE and needs
      further study. The panel suggested that an important improvement or response
      could be a 15% decrease in the FSS. The effect of several important confounding
      factors of fatigue such as sleep disorders, depression, fibromyalgia, and anemia
      needs to be collected and reported.

PMID- 18050226
TI  - Increased apoptosis of peripheral blood lymphocytes and its association with
      interleukin-18 in patients with active untreated adult-onset Still's disease.
AB  - OBJECTIVE: To determine spontaneous and activation-induced apoptosis of
      peripheral blood lymphocytes (PBLs) from patients with active untreated adult
      onset Still's disease (AOSD) and to examine the role of interleukin-18 (IL-18)
      involved in the apoptosis related to this disease. METHODS: The percentages of
      spontaneous and IL-18-stimulated apoptotic lymphocytes in peripheral blood of 20
      patients with active untreated AOSD, 20 with active untreated systemic lupus
      erythematosus (SLE), and 20 healthy controls were determined using annexin
      V/propidium iodide staining and flow cytometry. Serum IL-18 levels were measured
      using enzyme-linked immunosorbent assay. The transcripts of caspase 3 gene and
      apoptosis-regulating genes, including Fas, FasL, Bcl-2, and p53 in IL-18-treated
      peripheral blood mononuclear cells (PBMCs) from 8 AOSD patients, 4 SLE patients,
      and 4 healthy controls, were examined by real-time quantitative polymerase chain
      reaction. RESULTS: Significantly higher percentages of spontaneous and IL-18
      stimulated apoptotic PBLs were found in patients with active untreated AOSD and
      those with active untreated SLE than in healthy controls. The percentages of
      spontaneous and IL-18-stimulated apoptotic lymphocytes correlated positively with
      clinical activity scores and serum IL-18 levels for AOSD patients and SLE
      patients. The percentages of spontaneous and activation-induced apoptotic PBLs
      significantly declined, paralleling clinical remission and the decrease in serum
      IL-18 levels after effective therapy in AOSD patients. Up-regulation of FasL and
      p53 transcripts was demonstrated in IL-18-treated PBMCs from AOSD patients and
      SLE patients in a dose-dependent manner. CONCLUSION: The increased apoptosis of
      PBLs from AOSD patients may be associated with the effect of IL-18 through up
      regulation of FasL and p53 transcripts.

PMID- 18050227
TI  - Racial/ethnic disparities in patient-reported nonsteroidal antiinflammatory drug
      (NSAID) risk awareness, patient-doctor NSAID risk communication, and NSAID risk
      behavior.
AB  - OBJECTIVE: Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used and
      frequently lead to serious adverse events. Little is known about NSAID-related
      ethnic/racial disparities. We focused on differences in patient NSAID risk
      awareness, patient-doctor NSAID risk communication, and NSAID risk-avoidance
      behavior. METHODS: We performed a cross-sectional analysis of survey data from
      the Alabama NSAID Patient Safety Study. Eligible patients were > or = 65 years
      old and currently taking prescription NSAIDs (Rx NSAIDS). Generalized linear
      latent and mixed models accounted for nesting of patients within physicians.
      RESULTS: Of all 404 participants, 32% were African American and 73% were female.
      The mean +/- SD age was 72.8 +/- 7.5 years, and 64% reported an annual household
      income <$20,000. African American patients were less likely than white patients
      to recognize any risk associated with over-the-counter (OTC) NSAIDs (13.3% versus
      29.3%; P = 0.001) and Rx NSAIDs (31.3% versus 49.6%; P = 0.001), report that
      their doctor discussed possible NSAID-related gastrointestinal problems (38.0%
      versus 52.4%; P = 0.007), and take medications to reduce ulcer risk (30.5% versus
      50.2%; P = 0.001). Patients with lower income and education reported
      significantly less risk awareness for OTC and Rx NSAIDs. Racial/ethnic
      differences persisted after adjusting for multiple confounders. CONCLUSION: In
      this community-based study of low income elderly individuals receiving NSAIDs, we
      identified important racial/ethnic differences in risk awareness, communication,
      and behavior. Additional efforts are needed to promote safe NSAID use and reduce
      ethnic/racial disparities.

PMID- 18050228
TI  - Subspecialty choice: why did you become a rheumatologist?
AB  - OBJECTIVE: To determine the reasons trainees choose rheumatology as a
      subspecialty and to review the literature on career choices among physicians,
      particularly regarding the choice of subspecialty. METHODS: A questionnaire was
      designed to identify and analyze factors that influence rheumatology fellows to
      join the field of rheumatology. The questionnaire was administered online and
      answers were collated through the American College of Rheumatology Training and
      Workforce Committee, Subcommittee on Medical Student and Resident Recruitment. We
      reviewed the medical literature, using Medline and PubMed to find references to
      career choice among medical trainees. RESULTS: The majority of rheumatology
      fellows had their initial exposure to rheumatology as second-year and third-year
      medical students, and >75% solidified their decision during internship and
      residency. Clinical rotations in rheumatology and exposure to role models and
      mentors were the most influential factors. Approximately 40% of rheumatology
      fellows cite their intellectual interest in the field as the most important
      contributor to their decision. CONCLUSION: Career decision-making occurs
      throughout medical training. Exposure to clinical experiences and mentors are
      particularly influential and may have an impact during medical school, as well as
      during internal medicine residency training. These findings suggest that there
      are a variety of opportunities throughout medical training to influence career
      decision-making and improve recruitment into rheumatology. Additional financial
      resources that support recruitment efforts may be required, and followup studies
      assessing the effects of these efforts should be done.

PMID- 18050229
TI  - Small-vessel and medium-vessel vasculitis.

PMID- 18050230
TI  - Sensitivity of the classification of psoriatic arthritis criteria in early
      psoriatic arthritis.

PMID- 18050231
TI  - Delay in imaging versus clinical response: a rationale for prolonged treatment
      with anti-tumor necrosis factor medication in early rheumatoid arthritis.

PMID- 18050232
TI  - Short digits...what's up?

PMID- 18050233
TI  - Switching tumor necrosis factor alpha inhibitors in HLA-B27-associated severe
      heel enthesitis.

PMID- 18050236
TI  - Potential treatment of calciphylaxis with vitamin K(2): Comment on the article by
      Jacobs-Kosmin and DeHoratius.

PMID- 18050238
TI  - Circulating levels of tumor necrosis factor receptors are highly predictive of
      mortality in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether circulating levels of soluble tumor necrosis
      factor receptors (sTNFR) are predictive of mortality in rheumatoid arthritis
      (RA). METHODS: Levels of sTNFRI and sTNFRII at study entry were quantified using
      enzyme-linked immunosorbent assays in sera from 401 white patients with RA
      followed up for 13 years. Patients were tracked via the National Health Service
      Central Register, and the relationship between sTNFR levels and mortality was
      analyzed using a Cox proportional hazards regression model. Hazard ratios (HRs)
      and 95% confidence intervals (95% CIs) were calculated. RESULTS: At the end of
      the followup period, 132 (32.9%) of 401 patients had died. Of these, 64 (48.5%)
      died of cardiovascular disease (CVD). Significant associations between all-cause
      mortality and baseline levels of sTNFRI and sTNFRII were identified in men (HR
      1.7 [95% CI 1.2-2.4] and HR 1.18 [95% CI 1.05-1.32], respectively) and women (HR
      1.33 [95% CI 0.99-1.8] and HR 1.14 [95% CI 1.02-1.28], respectively). Analysis
      including levels of both sTNFRI and sTNFRII indicated that the sTNFRII level was
      the best overall predictor of mortality. Multivariate analysis also revealed that
      the sTNFRII level was a predictor of all-cause and CVD mortality independently of
      age, sex, disease duration, C-reactive protein level, erythrocyte sedimentation
      rate, rheumatoid factor, nodular disease, modified Health Assessment
      Questionnaire score, taking CVD drugs, and smoking. CONCLUSION: Our data indicate
      that serum levels of sTNFR are powerful predictors of mortality in RA. Elevated
      levels are particularly associated with mortality due to CVD and may be useful
      for identifying patients at increased risk of premature death.

PMID- 18050240
TI  - Characterization of in vitro metabolites of deoxypodophyllotoxin in human and rat
      liver microsomes using liquid chromatography/tandem mass spectrometry.
AB  - The in vitro metabolism of deoxypodophyllotoxin (DPT), a medicinal herbal product
      isolated from Anthriscus sylvestris (Apiaceae), was investigated in rats and
      human microsomes and human recombinant cDNA-expressed CYPs. The incubation of DPT
      with pooled human microsomes in the presence of NADPH generated five metabolites
      while its incubation with dexamethasone (Dex)-induced rat liver resulted in seven
      metabolites (M1-M7) with major metabolic reactions including mono-hydroxylation,
      O-demethylation and demethylenation. Reasonable structures of the seven
      metabolites of DPT could be proposed, based on the electrospray tandem mass
      spectra. Chemical inhibition by ketoconazole and metabolism studies with human
      recombinant cDNA-expressed CYPs indicated that CYP 3A4 and 2C19 are the major CYP
      isozymes in the metabolism of DPT in human liver microsomes.

PMID- 18050241
TI  - Analysis of biologically active compounds in water by ultra-performance liquid
      chromatography quadrupole time-of-flight mass spectrometry.
AB  - A new method based on ultra-performance liquid chromatography (UPLC) quadrupole
      time-of-flight mass spectrometry ((Q-ToF)-MS) was developed for the analysis of
      32 biologically active compounds including anti-inflammatories, analgesics, lipid
      regulators, psychiatric drugs, anti-ulcer agents, antibiotics, beta-blockers and
      phytoestrogens. This new method allows chromatographic analysis in 14 min, with
      instrumental detection limits from 2 to 84 pg, and limits of quantification
      ranging from 0.1 to 15 ng/L in tap water, and from 2 to 300 ng/L in wastewater.
      The potential of liquid chromatography with triple quadrupole mass spectrometry
      (LC/QqQ-MS) was compared with that of UPLC/(Q-ToF)-MS for the analysis of
      biologically active compounds in water samples. LC/Q-ToF provides accurate mass
      information and a significantly higher mass resolution than quadrupole analyzers.
      The available mass resolution of ToF instruments diminishes the problem of
      isobaric interferences and helps the analysis of trace compounds in complex
      samples. In this work UPLC/Q-ToF chromatograms were recorded containing full scan
      spectral data. The m/z values of analytes were extracted from the total ion
      chromatogram (TIC) and the accurate masses of the compounds were obtained. In
      addition, to increase the selectivity of ToF measurements a narrow accurate mass
      interval (20 m m/z units mass window) was used to reconstruct the chromatographic
      traces. However, regarding quantitative performance in terms of dynamic range and
      limits of detection (LODs), typical LODs achieved by QqQ instruments operating in
      multiple-reaction monitoring (MRM) mode ranged from 1 to 50 ng/L in wastewater,
      and the linear response for QqQ instruments generally covers three orders of
      magnitude. This is an important advantage over ToF instruments and one of the
      reasons why QqQ instruments are widely used in quantitative environmental
      analysis.

PMID- 18050242
TI  - Clinical significance of a persistent left superior vena cava.

PMID- 18050243
TI  - One-week Short-Term Life Review interview can improve spiritual well-being of
      terminally ill cancer patients.
AB  - PURPOSE: The primary aim of this study was to assess the efficacy of the Short
      Term Life Review on the spiritual well-being, as well as anxiety, depression,
      suffering, and happiness of terminally ill cancer patients. METHOD: Thirty
      patients reviewed their lives in the first session and they confirmed the
      contents in the album based on the life review in the second session. Duration of
      the treatment was one week. Measurement instruments included Functional
      Assessment Chronic Illness Therapy-Spiritual (FACIT-Sp), Hospital Anxiety and
      Depression Scale (HADS), Numeric Rating Scales of Suffering (from 0 to 6) and
      Happiness (from 1 to 7). RESULTS: After the therapy, the mean FACIT-Sp scores
      increased from 16+/-8.2 to 24+/-7.1, anxiety score significantly decreased from
      6.8+/-4.7 to 3.0+/-2.2, depression score significantly decreased from 10.2+/-4.7
      to 6.6+/-4.1, suffering score significantly decreased from 3.4+/-1.9 to 1.8+/
      1.4, and happiness score significantly increased from 4.6+/-1.9 to 5.6+/-1.6.
      Total HADS scores significantly decreased from 17+/-8.6 to 9.5+/-5.4. CONCLUSION:
      The Short-Term Life Review is feasible and may be effective in improving the
      spiritual and psychosocial well-being of terminally ill cancer patients.

PMID- 18050244
TI  - A binary matrix of 2,5-dihydroxybenzoic acid and glycerol produces homogenous
      sample preparations for matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - We introduce a two-component matrix for ultraviolet matrix-assisted laser
      desorption/ionization mass spectrometry (UV-MALDI-MS) that consists of 2,5
      dihydroxybenzoic acid (DHB) and glycerol. Upon slow evaporation of residual
      water/methanol solvents in a pre-vacuum chamber sample preparations are obtained
      that exhibit a homogeneous morphology with analyte-matrix crystals evenly
      distributed over the whole sample spot. At a molar DHB/glycerol ratio of
      approximately 1:5, the crystals range in length from approximately 100 to 300
      microm and are about 15-30 microm wide. Mass spectra of peptides, proteins, and
      an oligosaccharide are presented and compared with those recorded from standard
      dried-droplet DHB matrix. The ion signals show a reproducibility of the order of
      10-15% when scanning the surface of an individual sample or even different
      samples that contain the same amount of peptide, A close to linear relationship
      between peptide concentration and the corresponding peptide ion signal is found
      over three orders of magnitude of sample prepared. However, when a fixed position
      is irradiated with a large number of laser pulses, a monotonous decay of peptide
      ion signal with time is observed. Potentially, the binary matrix will be
      especially useful for the analysis of samples that are stabilized in buffered
      aqueous glycerol solution and preliminary results addressing this aspect are
      shown.

PMID- 18050245
TI  - Randomized placebo-controlled trial of escitalopram and venlafaxine XR in the
      treatment of generalized anxiety disorder.
AB  - Generalized anxiety disorder (GAD) is a highly prevalent and disabling condition.
      Escitalopram and venlafaxine extended release (XR) both are indicated for the
      treatment of GAD. Outpatients (ages 18-65 years) with DSM-IV-defined GAD
      (Hamilton Anxiety Scale [HAMA] >or=20) were eligible to participate in this
      randomized, double-blind, placebo-controlled, multicenter, flexible-dose trial.
      Following randomization, patients received 8 weeks of double-blind treatment with
      escitalopram (10-20 mg/day; N=127), venlafaxine XR (75-225 mg/day; N=129), or
      placebo (N=136). The primary efficacy parameter was mean change from baseline at
      week 8 in HAMA total score, using the Last Observation Carried Forward (LOCF)
      approach. Secondary efficacy parameters were HAMA psychic anxiety subscale,
      Clinical Global Impressions of Severity (CGI-S) and Improvement (CGI-I) scales.
      Treatment was completed by 77% of patients. The least square mean difference for
      change from baseline at week 8 in HAMA total score for escitalopram and
      venlafaxine XR versus placebo were -1.52 (P=.09) and -2.27 (P=.01), respectively,
      for LOCF, and -1.92 (P=.033) and -3.02 (P=.001), respectively, for Observed Cases
      (OC). On all secondary parameters, both active treatments were significantly
      superior to placebo on the LOCF and OC analyses. Discontinuation due to adverse
      events was not different for escitalopram versus placebo (7 versus 5%, P=.61),
      but was significantly greater for venlafaxine XR (13%) versus placebo (P=.03).
      Venlafaxine XR, but not escitalopram, separated from placebo on the primary
      efficacy measure, using the LOCF approach. However, overall efficacy analyses
      suggest that escitalopram and venlafaxine XR are both effective treatments for
      GAD. Escitalopram was better tolerated.

PMID- 18050246
TI  - Functional magnetic resonance imaging assessment of cognitive function in
      childhood-onset systemic lupus erythematosus: a pilot study.
AB  - OBJECTIVE: To investigate changes in brain activation patterns detected by
      functional magnetic resonance imaging (FMRI), and the relationship between FMRI
      activation patterns and results of formal neuropsychological testing, in patients
      with childhood-onset systemic lupus erythematosus (SLE). METHODS: Ten patients
      with childhood-onset SLE underwent formal neuropsychological testing and FMRI
      using 3 paradigms: a continuous performance task (CPT) to evaluate attention, an
      N-Back task to assess working memory, and verb generation to evaluate language
      processing. Composite Z maps were generated to summarize the brain activation
      patterns for each FMRI paradigm in patients with childhood-onset SLE and to
      compare these patterns with those observed in healthy controls. Between-group
      comparison Z maps showing differences in activation between childhood-onset SLE
      patients and controls were generated, using a significance level of P < 0.05 in a
      general linear model. RESULTS: Compared with the control group, the childhood
      onset SLE group showed statistically significant increased activation of brain
      areas involved in the CPT, N-Back, and verb generation tasks. In contrast, in the
      absence of active stimulus, e.g., during times of the paradigm control tasks,
      childhood-onset SLE patients consistently undersuppressed activity in the
      expected brain areas. Activation in selected cortical areas was found to
      correlate negatively with results of a subset of individual neuropsychological
      test scores. CONCLUSION: FMRI abnormalities are present in childhood-onset SLE,
      manifesting as an imbalance between active and inhibitory responses to an array
      of stimuli. Differences in brain activation patterns compared with those observed
      in controls suggest that childhood-onset SLE may be associated with abnormalities
      in white matter connectivity resulting in neuronal network dysfunction, rather
      than injury of specific gray matter areas.

PMID- 18050247
TI  - Identification of novel susceptibility genes in childhood-onset systemic lupus
      erythematosus using a uniquely designed candidate gene pathway platform.
AB  - OBJECTIVE: Childhood-onset systemic lupus erythematosus (SLE) presents a unique
      subgroup of patients for genetic study. The present study was undertaken to
      identify susceptibility genes contributing to SLE, using a novel candidate gene
      pathway microarray platform to investigate gene expression in patients with
      childhood-onset SLE and both of their parents. METHODS: Utilizing bioinformatic
      tools, a platform of 9,412 single-nucleotide polymorphisms (SNPs) from 1,204
      genes was designed and validated. Molecular inversion probes and high-throughput
      SNP technologies were used for assay development. Seven hundred fifty three
      subjects, corresponding to 251 full trios of childhood-onset SLE families, were
      genotyped and analyzed using transmission disequilibrium testing (TDT) and
      multitest corrections. RESULTS: Family-based TDT showed a significant association
      of SLE with a N673S polymorphism in the P-selectin gene (SELP) (P = 5.74 x 10(
      6)) and a C203S polymorphism in the interleukin-1 receptor-associated kinase 1
      gene (IRAK1) (P = 9.58 x 10(-6)). These 2 SNPs had a false discovery rate for
      multitest correction of <0.05, and therefore a >95% probability of being
      considered as proven. Furthermore, 7 additional SNPs showed q values of <0.5,
      suggesting association with SLE and providing a direction for followup studies.
      These additional genes notably included TNFRSF6 (Fas) and IRF5, supporting
      previous findings of their association with SLE pathogenesis. CONCLUSION: SELP
      and IRAK1 were identified as novel SLE-associated genes with a high degree of
      significance, suggesting new directions in understanding the pathogenesis of SLE.
      The overall design and results of this study demonstrate that the candidate gene
      pathway microarray platform used provides a novel and powerful approach that is
      generally applicable in identifying genetic foundations of complex diseases.

PMID- 18050248
TI  - Acute Kawasaki disease is associated with reverse regulation of soluble receptor
      for advance glycation end products and its proinflammatory ligand S100A12.
AB  - OBJECTIVE: Receptor for advanced glycation end products (RAGE) serves as a
      pattern recognition receptor for several endogenous ligands that are potent
      inducers of inflammation. By activating endothelial cells and leukocytes, RAGE
      augments recruitment of leukocytes to sites of inflammation, which is a key
      process, especially in vasculitis. Soluble RAGE (sRAGE) acts as a naturally
      occurring inhibitor of RAGE by neutralizing proinflammatory ligands, e.g.,
      S100A12. This neutrophil-derived protein has been reported to be associated with
      Kawasaki disease (KD) and to provoke proinflammatory responses. The aim of this
      study was to investigate circulating sRAGE in an acute inflammatory disorder and
      to compare these data directly with concentrations of the proinflammatory RAGE
      ligand S100A12. METHODS: Serum concentrations of sRAGE and S100A12 were analyzed
      by specific enzyme-linked immunosorbent assays in 50 children with KD, and
      additionally in 39 patients with juvenile idiopathic arthritis (JIA). In 28 of
      the patients with KD, levels were analyzed longitudinally over the course of the
      disease. RESULTS: Patients with KD and those with systemic-onset JIA had
      decreased levels of sRAGE during active disease, especially those patients with
      KD who were more severely affected and not responding to treatment. In addition,
      the level of sRAGE correlated negatively with the level of proinflammatory
      S100A12. After intravenous immunoglobulin (IVIG) therapy in patients with KD, the
      S100A12:sRAGE ratio was significantly different between responders and
      nonresponders. CONCLUSION: Inverse regulation of both sRAGE and its
      proinflammatory ligand S100A12 seems to be a relevant molecular mechanism
      promoting systemic inflammation. Calculating the S100A12:sRAGE ratio might help
      to detect patients with KD who are at risk of being unresponsive to IVIG therapy.

PMID- 18050249
TI  - Elevated CD16 expression by monocytes from patients with tumor necrosis factor
      receptor-associated periodic syndrome.
AB  - OBJECTIVE: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is
      an inherited autosomal-dominant autoinflammatory condition caused by mutations in
      the ectodomain of the 55-kd tumor necrosis factor (TNF) receptor superfamily 1A.
      Proinflammatory blood monocytes with the phenotype CD14+,CD16+,HLA-DR++ are a
      major source of TNF, and the number of such monocytes is increased during
      infection and inflammation. The aim of this study was to investigate whether the
      expression of circulating CD16+ monocytes is affected in patients with TRAPS.
      METHODS: Peripheral blood obtained from patients with TRAPS and healthy control
      subjects was stained with monoclonal antibodies to detect CD14++,CD16- monocytes
      and CD14+,CD16+ monocytes, using flow cytometry. Lipopolysaccharide-induced TNF
      production was measured by intracellular cytokine staining. Activation-induced
      shedding of CD16 was investigated by treating blood samples with phorbol
      myristate acetate. RESULTS: The level of CD16 expression by CD14+,CD16+
      monocytes, but not their absolute number, was significantly elevated in patients
      with TRAPS, even though the patients were not experiencing clinically overt
      episodes of autoinflammation at the time of sampling. These findings are similar
      to those for the C-reactive protein levels and erythrocyte sedimentation rates in
      the same patients. The enhanced level of CD16 expression by monocytes from
      patients with TRAPS was not attributable to a defect in activation-induced
      shedding of CD16. The CD14+,CD16+ monocytes were the predominant source of TNF in
      both patients and healthy control subjects. CONCLUSION: The level of CD16
      expression by monocytes was elevated in patients with TRAPS, as a feature of the
      underlying constitutive inflammation status.

PMID- 18050250
TI  - Endothelin is a downstream mediator of profibrotic responses to transforming
      growth factor beta in human lung fibroblasts.
AB  - OBJECTIVE: Fibrosis is excessive scarring caused by the accumulation and
      contraction of extracellular matrix proteins and is a common end pathway in many
      chronic diseases, including scleroderma (systemic sclerosis [SSc]). Indeed,
      pulmonary fibrosis is a major cause of death in SSc. Transforming growth factor
      beta (TGFbeta) induces endothelin 1 (ET-1) in human lung fibroblasts by a Smad
      independent, JNK-dependent mechanism. The goal of this study was to assess
      whether ET-1 is a downstream mediator of the profibrotic effects of TGFbeta in
      lung fibroblasts. METHODS: We used a specific endothelin receptor antagonist to
      determine whether ET-1 is a downstream mediator of TGFbeta responses in lung
      fibroblasts, using microarray technology, real-time polymerase chain reaction,
      and Western blot analyses. RESULTS: The ability of TGFbeta to induce the
      expression of a cohort of profibrotic genes, including type I collagen,
      fibronectin, and CCN2, and to contract a collagen gel matrix, depends on ET-1.
      CONCLUSION: ET-1 contributes to the ability of TGFbeta to promote a profibrotic
      phenotype in human lung fibroblasts, consistent with the notion that endothelin
      receptor antagonism may be beneficial in controlling fibrogenic responses in lung
      fibroblasts.

PMID- 18050251
TI  - Persistence of abnormal bronchoalveolar lavage findings after cyclophosphamide
      treatment in scleroderma patients with interstitial lung disease.
AB  - OBJECTIVE: Bronchoalveolar lavage (BAL) is a procedure for sampling the terminal
      airspace cell population to diagnose alveolitis, a condition that predicts
      changes in lung function in scleroderma patients. Cyclophosphamide (CYC)
      stabilizes the progression of lung disease in some, but not all, patients with
      active alveolitis. However, it is unknown whether the BAL fluid cell count
      obtained after CYC treatment of alveolitis predicts long-term lung function
      outcomes and can therefore be used to assist in therapeutic decision-making. The
      purpose of this study was to determine whether CYC therapy for active lung
      disease alters BAL fluid neutrophil and eosinophil counts and whether the
      persistence of abnormal BAL findings after CYC therapy predicts a decline in lung
      function in patients with scleroderma and interstitial lung disease (ILD).
      METHODS: We systematically reviewed the records of scleroderma patients who had
      active ILD, as evidenced by neutrophilia or eosinophilia on BAL fluid analysis
      before CYC therapy and on repeat analysis after completion of CYC. Pulmonary
      function tests (PFTs) were performed before initiation of therapy, at completion
      of therapy, and during long-term followup (mean +/- SD 3.6 +/- 1.94 years).
      RESULTS: Of the 25 study patients, in only 6 did the BAL fluid cell counts
      normalize after CYC therapy. No significant differences were observed between the
      proportions of patients who had a > or =10% decline in the % predicted DLCO or
      FVC on the second set of PFTs and had abnormal findings on followup BAL fluid
      analysis. During long-term followup, patients with persistent alveolitis had a
      decline in lung function (mean +/- SD change in % predicted FVC -0.6 +/- 10.8
      liters and mean +/- SD change in % predicted DLCO -4.7 +/- 21.43 ml/minute/mm
      Hg), but their lung function did not significantly differ from that in patients
      whose BAL fluid cell counts had normalized (P = 0.70 and P = 0.62, respectively).
      CONCLUSION: Persistently abnormal results on BAL fluid analysis following CYC
      treatment is a common finding and does not predict a subsequent decline in lung
      function.

PMID- 18050252
TI  - Hypoxia-induced increase in the production of extracellular matrix proteins in
      systemic sclerosis.
AB  - OBJECTIVE: Insufficient angiogenesis with tissue ischemia and accumulation of
      extracellular matrix are hallmarks of systemic sclerosis (SSc). Based on the
      severely decreased oxygen levels in the skin of patients with SSc, we aimed to
      investigate the role of hypoxia in the pathogenesis of SSc. METHODS: Subtractive
      hybridization was used to compare gene expression in dermal fibroblasts under
      hypoxic and normoxic conditions. Dermal fibroblasts were further characterized by
      exposure to different concentrations of oxygen and for different time periods as
      well as by interference with hypoxia-inducible factor 1alpha (HIF-1alpha). The
      systemic normobaric hypoxia model in mice was used for in vivo analyses. RESULTS:
      Several extracellular matrix proteins and genes involved in extracellular matrix
      turnover, such as thrombospondin 1, proalpha2(I) collagen, fibronectin 1, insulin
      like growth factor binding protein 3, and transforming growth factor beta-induced
      protein, were induced by hypoxia in SSc and healthy dermal fibroblasts. The
      induction of these genes was time- and dose-dependent. Experiments with HIF
      1alpha-knockout mouse embryonic fibroblasts, deferoxamine/cobalt ions as chemical
      stabilizers of HIF-1alpha, and HIF-1alpha small interfering RNA consistently
      showed that extracellular matrix genes are induced in dermal fibroblasts by HIF
      1alpha-dependent, as well as HIF-1alpha-independent, mechanisms. Using the
      systemic normobaric hypoxia mouse model, we demonstrated that dermal hypoxia
      leads to the induction of the identified extracellular matrix genes in vivo after
      both short exposure and prolonged exposure to hypoxia. CONCLUSION: These data
      show that hypoxia contributes directly to the progression of fibrosis in patients
      with SSc by increasing the release of major extracellular matrix proteins.
      Targeting of hypoxia pathways might therefore be of therapeutic value in patients
      with SSc.

PMID- 18050257
TI  - Osteoporosis, vitamin D deficiency, and supplementation in juvenile systemic
      lupus erythematosus: comment on the article by Compeyrot-Lacassagne et al.

PMID- 18050253
TI  - Drug-specific and time-dependent risks of bacterial infection among patients with
      rheumatoid arthritis who were exposed to tumor necrosis factor alpha antagonists.

PMID- 18050258
TI  - Serum amyloid P and fibrosis in systemic sclerosis: comment on the article by
      Tennent et al.

PMID- 18050260
TI  - Cancer, mental disorders, suicidal ideation and attempts in a large community
      sample.
AB  - PURPOSE: To determine the association between cancer diagnosis, mental disorders
      and suicidal behavior among community dwelling adults. METHODS: Data were drawn
      from the nationally representative Canadian Community Health Survey Cycle 1.2
      (N=36 984, response rate 77%, age 15+). Respondents were grouped into three age
      groups (15-54, 55-74, and 75+ years), and multiple regression analyses were
      conducted to examine the relationship between cancer and mental disorders:
      unadjusted and adjusted for sociodemographics, social supports and other mental
      disorders. RESULTS: Among respondents aged 15-54, cancer was associated with
      increased odds of major depression (odds ratio [OR]=3.18; 95% confidence interval
      [CI]: 1.69-5.96), panic attacks (OR=2.15; 95% CI: 1.22-3.77) and any mental
      disorder. Among respondents aged 55-75, cancer was associated with increased odds
      of agoraphobia (OR=5.94; 95% CI: 1.68-21.03) and decreased odds of social phobia
      (OR=0.22; 95% CI: 0.06-0.80). Cancer was not associated with any mental disorder
      in the 75+ age group. Results persisted after adjustments for the covariates.
      Suicidal ideation was associated with cancer in the 55-74 age group (OR=5.07; 95%
      CI: 1.25-20.47) in unadjusted models; however, this relationship became non
      significant when adjusting for the other covariates. CONCLUSION: Clinicians
      should consider screening for depression and panic disorder in young, community
      dwelling patients with cancer.

PMID- 18050261
TI  - Study on the formation of an amoxicillin adduct with methanol using electrospray
      ion trap tandem mass spectrometry.
AB  - The possibility of using the protonated methanol-adduct of antimicrobial
      amoxicillin for its identification and quantification at residue levels has been
      investigated, since it is impossible to completely suppress the formation of
      these adducts when methanol is present in the solvent system. This process has
      been monitored over time and as a function of concentration. It was determined
      that adducts were instantly formed and that the abundance of the protonated
      methanol-adduct at m/z 398 increased at the expense of the protonated molecule
      m/z 366 with storage time. The effect of several common solvents and mobile-phase
      additives on the ionization efficiency of amoxicillin and the formation of the
      methanol adduct has also been investigated. It was shown that the mass spectra of
      amoxicillin were strongly influenced by the solvent in which the analyte is
      dissolved and by the analyte concentration, as well as by the composition of
      mobile phase. Methanol was determined to be the best spray solvent, as it
      provided spectra with the lowest abundance of dimer ions. It was also determined
      that acetic acid as the mobile-phase additive provided the highest signal
      intensities, while ammonium acetate should not be used as an additive for the
      determination of amoxicillin at residue levels. Using high-performance liquid
      chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS),
      fragmentation of the protonated molecules and the protonated methanol-adduct
      ions, in both positive and negative ion mode, has been performed. The
      fragmentation was stable and strong product ion spectra were obtained. The
      linearity of the MS detector response, and that of the chromatographic method,
      was tested. Due to the linear behaviour it was concluded that the protonated
      methanol-adduct ion can be used for analytical purposes, i.e. for identification
      and quantification of amoxicillin at trace levels.

PMID- 18050262
TI  - Serotonin transporter polymorphism (5-HTTLPR) association with melancholic
      depression: a female specific effect?
AB  - Earlier studies yielded inconsistent results on the association between variation
      in the serotonin transporter (5-HTT) gene and depression, with evidence for a
      differential effect of the 5-HTTLPR on melancholic versus atypical depression. To
      further delineate the impact of 5-HTT gene variation on psychopathology in
      depression, in this analysis the influence of the 5-HTTLPR and the functionally
      closely related 5-HTT rs25531 was investigated in 340 Caucasian patients with a
      major depressive episode (DSM-IV) with particular attention to the subtype of
      depression (melancholic depression versus atypical depression) applying logistic
      regression models adjusted for age and gender. The homozygous, more active 5
      HTTLPR LL genotype was significantly associated with melancholic depression (odds
      ratio, OR, 1.7; 95% confidence interval, CI, 1.1-2.6; P=0.04), with the effect
      originating in the female subgroup of patients (OR 1.9; 95%CI 1.0-3.4; P=0.05).
      Also, the more active 5-HTTLPR/5-HTT rs25531 haplotype L(A)L(A) conveyed a
      significant risk for melancholic depression (OR 2.0; 95%CI 1.3-3.1; P=0.001),
      again only in the female subsample of patients (OR 2.1; 95%CI 1.1-4.1; P=0.02).
      The present results provide further support for an association of genetic
      variation increasing serotonin transporter activity with the melancholic subtype
      of depression as well as evidence for a potential female-specific mechanism
      underlying this effect.

PMID- 18050263
TI  - Maintaining and optimising anti-TNF therapy.

PMID- 18050266
TI  - Process intensification of whole-cell biocatalysis with ionic liquids.
AB  - The unique properties of room temperature ionic liquids such as non-volatility,
      nonflammability, and, in many cases, high thermal and chemical stability have
      made them an environmentally attractive alternative to organic solvents. Biphasic
      biocatalytic processes with nonmiscible liquid phases are usually applied with
      whole-cell biocatalysts to overcome low water solubility of substrates or
      products, inhibitory effects of the reactants on the biocatalyst, or low
      stability of substrates or products in the aqueous phase. The surprising
      noninvasive effects on cellular membranes of hydrophobic ionic liquids especially
      of those with hexafluorophosphate and bis(trifluoromethylsulfonyl)imide anions in
      biphasic ionic liquid/water systems make them superior to many organic solvents
      so far applied in whole-cell biotransformations. Impressive process
      intensification in simple biphasic batch processes was recently demonstrated on
      the examples of asymmetric synthesis with whole-cell biocatalysts, if the
      distribution coefficients of inhibitory substrates and products between ionic
      liquids and aqueous phase exceed a log D of about 2 (e.g., ketones and beta
      ketoesters with lipophilic side chains and their corresponding chiral alcohols).

PMID- 18050264
TI  - Ferutinin stability in human plasma and interaction with human serum albumin.
AB  - Ferutinin is a potent phytoestrogen extracted from plants of the genus Ferula.
      The biological activity of this sesquiterpene is associated with the
      esterification of p-hydroxybenzoic acid with the daucane alcohol,
      jaeschkeanadiol. A HPLC method was developed to investigate the stability of
      ferutinin in acidic and basic solutions (pH 1.5 and 9.0, respectively), in buffer
      (pH 7.4) as well as in serial dilutions of albumin and in human plasma. The
      degradation of ferutinin was relatively slow at physiological pH 7.4 compared
      with low or high pH. Ferutinin was fully stable in human plasma as well as in
      albumin solution and the stability increased with albumin concentration. The
      binding of ferutinin to albumin was investigated by fluorescence spectroscopy.
      Ferutinin decreased the fluorescence of HSA and that of the only tryptophan
      residue located in domain IIA. As a result of the interaction between ferutinin
      and albumin, the binding of bilirubin decreased. The stability of ferutinin in
      plasma is attributable to ferutinin-albumin binding.

PMID- 18050267
TI  - Alpha4/3 conotoxins: phylogenetic distribution, functional properties, and
      structure-function insights.
AB  - This review examines the alpha4/3 conotoxins as an example of molecular diversity
      in a class of compounds that have evolved in a group of closely related species
      in a single phylogenetic lineage. The species examined belong to Stephanoconus, a
      clade of Conus, a genus that contains 500-700 different species of carnivorous
      marine snails. We examine earlier work that describes the identification and
      characterization of alpha-ImI, the founding alpha4/3 toxin, and two other
      alpha4/3 toxins, alpha-ImII and alpha-RgIA. These three toxins all inhibit
      nicotinic acetylcholine receptors (nAChRs) belonging to a subset of nAChRs that
      are composed of only alpha subunits; they are, however, diverse in terms of the
      all-alpha subtype they preferentially antagonize and the receptor site that they
      bind to. We thus speculate that the alpha4/3 toxins may be a rich source of
      functionally diverse all-alpha subunit nAChR inhibitors. We review extensive work
      that has established a detailed model for alpha-ImI binding to one of its
      preferred nAChR subtypes (the alpha7 nAChR) and, by comparing the alpha-ImI,
      alpha-ImII and alpha-RgIA sequences demonstrate how structural features of
      alpha4/3 peptides that account for their diverse functional properties can be
      identified. This approach is extended to derive models of receptor-toxin binding
      that may account for the different subtype specificities of alpha4/3 peptides. We
      also speculate on how rational modification of alpha4/3 toxins may allow
      engineering of ligands with desired subtype specificities. The chemical diversity
      produced by the closely related animals in Stephanoconus is thus functionally
      differentiated, although structurally homologous.

PMID- 18050270
TI  - Requirement of secondary lymphoid tissues for the induction of primary and
      secondary T cell responses against Listeria monocytogenes.
AB  - Activation of naive T cells is tightly controlled and depends on cognate
      interactions with professional antigen-presenting cells. We analyzed dependency
      on secondary lymphoid tissues for the activation of naive and memory CD4(+) and
      CD8(+) T cells following primary and secondary Listeria monocytogenes infection,
      respectively. In splenectomized lymphotoxin-beta receptor-deficient mice, lacking
      all secondary lymphoid tissues, oral infection with L. monocytogenes failed to
      induce bacteria-specific CD4(+) and CD8(+) T cell responses. Treatment of
      splenectomized wild-type mice with FTY720, a drug that prevents egress of T cells
      from lymph nodes, also reduced T cell responses after oral L. monocytogenes
      infection and blocked T cell responses after intravenous infection. FTY720
      treated wild-type and lymphotoxin-beta receptor-deficient mice show only slightly
      impaired recall responses. However, T cell responses were profoundly inhibited
      when mice were splenectomized subsequently to recovery from primary infection. T
      cell transfer experiments demonstrated that the impaired secondary T cell
      response was not simply due to removal of a large fraction of memory T cells by
      splenectomy. Overall, these results indicate that not only primary T cell
      responses, but also secondary T cell responses, highly depend on the lymphoid
      environment for effective activation.

PMID- 18050271
TI  - Expression of PI(4,5)P2-binding proteins lowers the PI(4,5)P2level and inhibits
      FcgammaRIIA-mediated cell spreading and phagocytosis.
AB  - We found that FcgammaRII-mediated cell spreading and phagocytosis were correlated
      with an increase of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] level in
      cells. During the spreading, a long-lasting elevation of PI(4,5)P(2) and
      concomitant actin polymerization occurred. Filopodia and lamellae of spreading
      cells were enriched in phosphatidylinositol 4-phosphate 5-kinase Ialpha (PIP5
      kinase Ialpha) that colocalized with PI(4,5)P(2 )and actin filaments. Both
      spreading and phagocytosis were inhibited by expression of the C(374-440)
      fragment of PIP5-kinase Ialpha or the pleckstrin homology domain of phospholipase
      Cdelta(1 )(PLCdelta(1)-PH), two probes binding PI(4,5)P(2). These probes reduced
      the amount of PI(4,5)P(2) in the cells, evoked reorganization of the actin
      cytoskeleton and abolished PI(4,5)P(2) elevation during phagocytosis.
      Simultaneously, PLCdelta(1)-PH-GFP reduced the amount of PIP5-kinase Ialpha
      associated with the plasma membrane. In vitro studies demonstrated that PIP5
      kinase Ialpha-GST bound PI(4,5)P(2), phosphatidylinositol 4-monophosphate, and
      less efficiently, phosphatidic acid. The data suggest that the PLCdelta(1)-PH
      domain, and possibly also the C(374-440) fragment, when expressed in cells, can
      compete with endogenous PIP5-kinase Ialpha for PI(4,5)P(2 )binding in the plasma
      membrane leading eventually to PI(4,5)P(2) depletion.

PMID- 18050272
TI  - Characterization of the encephalitogenic immune response in a model of multiple
      sclerosis.
AB  - Experimental autoimmune encephalomyelitis (EAE) can be actively induced with the
      extracellular domain of myelin oligodendrocyte glycoprotein (MOG 1-125). MOG-EAE
      closely mimics multiple sclerosis (MS) especially as far as demyelination, lesion
      formation and axonal pathology are concerned. MOG 91-108 is the encephalitogenic
      stretch within MOG 1-125 in two EAE-susceptible MHC congenic LEW rat strains
      [LEW.1AV1 (RT1(av1)) and LEW.1N (RT1(n))] and DA (RT1(av1)) rats. In LEW.1AV1
      rats, disease could be induced with MOG 96-104 and to a lesser extent with MOG 98
      106, whereas in LEW.1N rats, only MOG 98-106 was pathogenic. Both peptides bound
      well to their restricting MHC class II molecules, i.e., RT1.D(n) in the LEW.1N
      rat and RT1.B(a) in the LEW.1AV1 rat. TCR spectratyping of MOG 91-108 immunized
      LEW.1N, LEW.1AV1 and DA rats revealed that MHC class II determined the TCRBV
      preference of CNS infiltrating T cells. The data demonstrate that the most
      critical factor in inducing MS like pathology is presentation of autoantigenic
      peptides on MHC class II molecules resulting in demyelination and axonal
      pathology.

PMID- 18050273
TI  - Natural killer T cells and innate immune B cells from lupus-prone NZB/W mice
      interact to generate IgM and IgG autoantibodies.
AB  - Lupus-prone NZB/W F1 mice develop glomerulonephritis after T helper cell
      dependent isotype switching of autoantibody secretion from IgM to IgG at about 6
      months of age. We compared innate immune natural killer (NK) T cells and
      conventional T cells for their capacity to help spontaneous in vitro
      immunoglobulin and autoantibody secretion of innate immune (B-1 and marginal
      zone) and conventional (follicular) B cell subsets from NZB/W F1 mice. We found
      that purified NKT cells not only increased spontaneous secretion of IgM and IgM
      anti-double-stranded (ds)DNA antibodies by B-1 and marginal zone B cells, but
      also facilitated secretion of IgG anti-dsDNA antibodies predominantly by B-1 B
      cells. Few IgM or IgG anti-dsDNA antibodies were secreted by follicular B cells,
      and conventional T cells failed to provide potent helper activity to any B cell
      subset. All combinations of T and B cell subsets from normal C57BL/6 mice failed
      to generate vigorous IgM and IgG secretion. NZB/W NKT cell helper activity was
      blocked by anti-CD1 and anti-CD40L mAb. In conclusion, direct interactions
      between innate immune T and B cells form a pathway for the development of IgM and
      IgG lupus autoantibody secretion in NZB/W mice.

PMID- 18050274
TI  - Elastic image registration of 2-D gels for differential and repeatability
      studies.
AB  - One of the main applications of electrophoretic 2-D gels is the analysis of
      differential responses between different conditions. For this reason, specific
      spots are present in one of the images, but not in the other. In some other
      occasions, the same experiment is repeated between 2 and 12 times in order to
      increase statistical significance. In both situations, one of the major
      difficulties of these analysis is that 2-D gels are affected by spatial
      distortions due to run-time differences and dye-front deformations, resulting in
      images that are significantly dissimilar not only because of their content, but
      also because of their geometry. In this technical brief, we show how to use free,
      state-of-the-art image registration and fusion algorithms developed by us for
      solving the problem of comparing differential expression profiles, or computing
      an "average" image from a series of virtually identical gels.

PMID- 18050275
TI  - Opposite pathobiochemical fate of pyruvate kinase and adenylate kinase in aged
      rat skeletal muscle as revealed by proteomic DIGE analysis.
AB  - Sarcopenia is the drastic loss of skeletal muscle mass and strength during
      ageing. In order to better understand the molecular pathogenesis of age-related
      muscle wasting, we have performed a DIGE analysis of young adult versus old rat
      skeletal muscle. Proteomic profiling revealed that out of 2493 separated 2-D
      spots, 69 proteins exhibited a drastically changed expression. Age-dependent
      alterations in protein abundance indicated dramatic changes in metabolism,
      contractile activity, myofibrillar remodelling and stress response. In contrast
      to decreased levels of pyruvate kinase (PK), enolase and phosphofructokinase, the
      mitochondrial ATP synthase, succinate dehydrogenase, malate dehydrogenase,
      isocitrate dehydrogenase and adenylate kinase (AK) were increased in senescent
      fibres. Higher expression levels of myoglobin and fatty acid binding-protein
      indicated a shift to more aerobic-oxidative metabolism in a slower-twitching aged
      fibre population. The drastic increase in alphaB-crystallin and myotilin
      demonstrated substantial filament remodelling during ageing. An immunoblotting
      survey of selected muscle proteins confirmed the pathobiochemical transition
      process in aged muscle metabolism. The proteomic analysis of aged muscle has
      identified a large cohort of new biomarkers of sarcopenia including opposite
      changes in PK and AK, which might be useful for the design of improved diagnostic
      procedures and/or therapeutic strategies to counteract ageing-induced muscle
      degeneration.

PMID- 18050277
TI  - Proteomic analysis of the proteins regulated by HrpB from the plant pathogenic
      bacterium Burkholderia glumae.
AB  - Plant pathogenic bacteria transfer effector proteins into plant cells via the
      hypersensitive response and pathogenicity (Hrp) type III protein secretion system
      (T3SS) during infection. The genes encoding the Hrp T3SS are expressed only under
      plant apoplast-mimicking conditions in an AraC-type transcriptional activator
      HrpB-dependent manner. To identify the proteins controlled by HrpB in
      Burkholderia glumae in vitro, we constitutively expressed hrpB and analyzed the
      proteins showing altered expression using 2-DE and ESI-MS/MS. Among 46 proteins
      exhibiting consistently altered expression, which were encoded by 34 different
      genes, 34 were secretory proteins and 12 were cytoplasmic. Twenty-eight of the
      secreted proteins showed increased accumulation, whereas the other six showed
      decreased accumulation. None of the HrpB-dependent proteins had significant
      homology to known T3SS-dependent proteins, except for HrpK from Pseudomonas
      syringae pv. syringae and two T3SS-associated cytoplasmic proteins from Ralstonia
      solanacearum. Twenty-one of the 34 genes had putative HrpB-binding sequences in
      their upstream regulatory regions. Secretion of all 34 extracellular proteins was
      independent of the Hrp T3SS, and 16 were secreted via a type II protein secretion
      system (T2SS). Mutants lacking the T2SS or Hrp T3SS produced toxoflavin but were
      less virulent to rice panicles, indicating the importance of these proteins in
      pathogenicity.

PMID- 18050278
TI  - Methodological aspects of in vitro sensing of L-glutamate in acute brain slices.
AB  - L-Glutamate is a major amino acid neurotransmitter in the central neuronal system
      of the mammalian brain and plays a vital role in brain development, synaptic
      plasticity, neurotoxicity, and neuropathological disorders. Despite technical
      limitations, progress is being made in sensing L-glutamate in vivo and in vitro.
      Sophisticated microsensors with the necessary spatial and temporal resolution
      have recently been emerging, which enable us to discern regional distribution,
      concentration levels, and temporal changes of L-glutamate in acute brain slices.
      The L-glutamate sensors for in vitro sensing have different structures and sizes,
      such as glass capillary-based enzyme sensors, polymer-coated enzyme sensors, and
      patch sensors based on natural sensing probes. The concentration of L-glutamate
      released in brain slices by chemical stimulation is markedly dependent on
      neuronal regions, types of stimulation, and sensing methods. Real- and long-time
      monitoring of L-glutamate in acute hippocampal slices is beginning to shed light
      on L-glutamate release related to the molecular mechanisms of long-term
      potentiation. Progress is also being made toward the visualization of L-glutamate
      release in acute hippocampal slices. The methodological aspects of in vitro
      sensing of L-glutamate are discussed.

PMID- 18050279
TI  - Cyclotrimerization reactions of arynes and strained cycloalkynes.
AB  - The use of arynes and related species as substrates in metal-catalyzed
      cycloaddition reactions leads to structurally interesting products. Palladium
      catalyzed cyclotrimerization of arynes provides a new method for the synthesis of
      polycyclic aromatic hydrocarbons. For instance, the chemoselective formal [2 + 2
      + 2] cocycloaddition of 2,3-triphenylynes with alkynes affords extended
      triphenylenes, which are good candidates to behave as liquid crystals.
      Cotrimerization of benzyne and electron-deficient alkenes selectively affords
      dihydrophenanthrenes or ortho-olefinated biaryls depending on the catalytic
      system employed. The use of 2,2'-bis(diphenylphosphino)-1,1'-binophythyl (BINAP)
      based palladium(0) catalysts in the cocyclotrimerization of 7-methoxynaphthalyne
      and dimethyl acetylenedicarboxylate affords an enantiomerically enriched
      tetrasubstituted pentahelicene, the first example of a metal-catalyzed
      enantioselective reaction involving arynes. Strained cyclic alkynes can also
      participate in the palladium-catalyzed cyclotrimerization reactions, which again
      lead to structurally interesting products.

PMID- 18050280
TI  - A history of research on yeasts 11. The study of solute transport: the first 90
      years, simple and facilitated diffusion(1).

PMID- 18050281
TI  - Extended left-sided pancreatectomy with spleen preservation.
AB  - BACKGROUND: Distal pancreatectomy (DP) is frequently performed with splenectomy,
      although splenectomy can be linked to various untoward effects, and sparing of
      the main splenic vessels (SVs) is not necessary for successful spleen
      preservation (SP). METHODS: We reviewed all DPs in a single-surgeon practice to
      assess feasibility and outcomes of SP. RESULTS: Between 1997 and 2007, 41 of 177
      pancreatic resections involved a DP (23%). There were 14 men (34%) and 27 women
      (66%), with a median age of 60 years (range: 34-86). Four procedures were en bloc
      resections, two total pancreatectomies, while eight of the remaining 35 DPs were
      performed laparoscopically. SP was accomplished in 33 of 34 possible cases (SP
      rate 97%), despite SV resection in 27 of these (82%). The postoperative
      complication rate was 24%, without death. Pancreatic fistulae occurred in two
      patients (5% of patients at risk), and one SPDP led to splenic infarct. No other
      clinically relevant problems specific to SP have become apparent. CONCLUSIONS:
      Pancreatic fistula rate and other outcomes in this small DP experience compare
      favorably to other DP series. Few spleen-specific complications and the
      radicality of resection support the liberal use of SP with SV resection,
      irrespective of an open or laparoscopic approach.

PMID- 18050282
TI  - Electrical impedance scanning as a new breast cancer risk stratification tool for
      young women.
AB  - BACKGROUND: Electrical impedance scanning (EIS) measures changes in breast tissue
      associated with breast cancer (Br-Ca) development. The T-Scan(tm2000 (ED is
      designed to use EIS to identify women ages 30-39 with elevated risk of breast
      cancer (i.e., T-Scan+ women). AIM: To estimate the relative probability of breast
      cancer in a T-Scan+ woman compared to a randomly selected young woman. METHODS: A
      prospective, two-cohort trial was conducted in pre-menopausal women. The
      Specificity (S(p))-Cohort evaluated T-Scan specificity in 1,751 asymptomatic
      women ages 30-39. The Sensitivity)S(n))-Cohort evaluated T-Scan sensitivity in
      390 women ages 45-30 scheduled for biopsy. Specificity, sensitivity, and
      conservative estimate of disease prevalence were used to calculate relative
      probability. RESULTS: In the S(p)-Cohort, 93 of 1,751 women were T-Scan+ (S(p) =
      94.7%; 95% CI: 93.7-95.7%). In the S(n)-Cohort, 23 of 87 biopsy-proven cancers
      were T-Scan+ (S(n) = 26.4%; 95% CI: 17.4-35.4%). Given S(p) = 94.7%, S(n) = 26.4%
      and prevalence of 1.5 cancers/1,000 women (ages 30-39), the relative probability
      of a T-Scan+ woman having Br-Ca is 4.95: (95% CI: 3.16-7.14). CONCLUSION: EIS can
      identify a subset of young women with a relative probability of breast cancer
      almost five times greater than in the population of young women at-large. T-Scan+
      women have a sufficiently high risk of Br-Ca to warrant further surveillance or
      imaging.

PMID- 18050283
TI  - Papillary thyroid microcarcinoma: prognostic factors and treatment.
AB  - BACKGROUND AND OBJECTIVES: Within the group of patients with papillary thyroid
      microcarcinoma (PTMC), the prognostic factors have not been well defined and the
      optimal treatment has not been proved. The aim of this study was to find out the
      factors associated with the tumor recurrence in the patients with PTMC. METHODS:
      A total of 228 patients with PTMC (189 females, 39 males; age 14-85 years, median
      46 years) were treated at our Institute between 1975 and 2006. The data on
      patients' gender, age, extent of disease, pathomorphological characteristics,
      therapy, locoregional control, disease-free survival and disease-specific
      survival were collected. Statistical correlation between possible prognostic
      factors and the duration of disease-free interval was analyzed by univariate and
      Cox's multivariate survival analysis. RESULTS: The tumor diameter ranged from 0.1
      to 10 mm (mean 6.1 mm). The median length of observation was 84 months (range 1
      385). During the follow-up period, the recurrence was diagnosed in 7 patients (6
      locoregional and 1 distant). Multivariate analysis showed that tumor size and
      lymph node metastases were independent prognostic factors for disease-free
      interval. CONCLUSIONS: Longer disease-free interval was found in the patients
      with a tumor diameter < or =6 mm and without lymph-node metastases.

PMID- 18050284
TI  - Predictors and outcomes of recurrent disease after a negative second look
      laparotomy.
AB  - BACKGROUND AND OBJECTIVES: To analyze the predictors and outcomes of recurrent
      disease in patients with epithelial ovarian carcinoma (EOC) after a negative
      second look laparotomy (SLL). METHODS: One hundred nine EOC patients with a
      negative SLL treated at Hacettepe Hospital were retrospectively analyzed.
      RESULTS: Of these patients, 70 (64.2%) had no evidence of disease during follow
      up while remaining 39 (35.8%) had recurrence. Majority of the recurrences (82.1%)
      were detected within the initial 2 years of the SLL procedure. Multivariate
      analysis revealed stage and grade of the disease to be the significant predictors
      for the recurrent disease (P < 0.01 and P = 0.025, respectively). A second
      analysis with respect to initial metastatic sites revealed omental metastatis was
      significantly associated with recurrent disease (P < 0.001). Survival of patients
      with a recurrent disease was significantly poorer and dropped abruptly once a
      recurrence is developed. CONCLUSIONS: Patients with initial omental metastasis,
      advanced stage and high grade tumors have highest risk for developing recurrences
      after a (-) SLL. Most of the recurrences develop during the initial 2 years
      following the (-) SLL and survival drops to less than 2 years once a recurrence
      is found.

PMID- 18050285
TI  - Function, disability, and health-related quality of life after allograft
      prosthesis composite reconstructions of the proximal femur.
AB  - BACKGROUND: Factors affecting function, disability and health-related quality of
      life after allograft-prosthesis composite reconstructions have been poorly
      studied. METHODS: Retrospective study of eighteen patients who underwent
      reconstruction with proximal femoral allograft-prosthesis composites and answered
      questionnaires to assess hip function (Postel and Merle d'Aubigne, self-reported
      Harris Hip Score), disability (Toronto Extremity Salvage Score), and health
      related quality of life (SF-36). RESULTS: The median Toronto Extremity Salvage
      Score was 76 (IQR: 48-85), the median self-reported Harris Hip Score was 90 (IQR:
      48-95) and the median Postel and Merle d'Aubigne score was 17 (IQR: 12-17). Older
      age, female gender, and presentation with a pathologic fracture were associated
      with increased disability and poorest function. The median Physical Component
      Summary score was 44 (IQR: 39-45) and Mental Component Summary scores were 49
      (IQR: 46-56). Male gender and recurrence of disease were associated with poorer
      health-related quality of life. There was a high degree of correlation between
      function, disability scores and Physical Component Summary score. CONCLUSIONS:
      Patients' characteristics at presentation such as age, gender, and occurrence of
      a pathologic fracture play an important role in determining disability, function,
      and health-related quality of life after allograft-prosthesis composite
      reconstruction of the proximal femur.

PMID- 18050286
TI  - Does sentinel node biopsy improve the management of endometrial cancer? Data from
      43 patients.
AB  - OBJECTIVES: To map sentinel lymph nodes (SLNs) detected by intracervical
      injection in patients with endometrial cancer and to determine the prevalence of
      node micrometastases. METHODS: Radionuclide and blue dye injections were used for
      SLN detection in 43 patients with clinical stage I endometrial cancer.
      Lymphoscintigraphy was done before surgery. Intraoperatively, the pelvic and para
      aortic territories were examined for blue and/or radioactive nodes. Pelvic
      lymphadenectomy was performed with or without para-aortic lymphadenectomy. SLNs
      stained with hematoxylin-eosin-saffron were examined and, when negative,
      evaluated using step sectioning and immunohistochemistry. RESULTS: Feasibility
      was 100%. No adverse effects occurred. SLNs were identified in 30 patients
      (69.8%), usually in an interiliac location (28/30 patients, 93.3%). SLNs were
      found only in the common iliac chain in 1 (3%) patient and in both the common
      iliac chain and promontory area in another (3%). No patients had para-aortic SLNs
      or SLNs confined to the promontory. Node metastases were identified in eight
      patients and were confined to SLNs in six. In 2 (2/30, 6%) patients, SLNs
      contained micrometastases. No false-negatives occurred. CONCLUSIONS:
      Intracervical injection of radionuclide and blue dye chiefly revealed pelvic
      SLNs. The prevalence of micrometastases was within the expected range.
      Comparisons with peritumoral injection are needed.

PMID- 18050287
TI  - The use of artificial dermis for surgical defects in the treatment of oral
      premalignant lesions.
AB  - BACKGROUND: This study investigated the application of an artificial dermis as a
      substitute for split-thickness skin graft in an oral mucosal defect after
      excision of a premalignant lesion. METHODS: We examined a total of 125 sites
      repaired with artificial dermis in 84 patients. Forty-one of 84 patients had two
      different defects and 43 had a single defect. Of 84 patients, there were 52 oral
      leukoplakia and 32 oral submucous fibrosis. RESULTS: Most patients chewed betel
      nuts (97.6%). Most of the premalignant lesions were located in the buccal mucosa
      (94%). The overall success rate was 100% without any or partial graft loss. The
      minor wound oozing occurred in three grafts (2.4%). No patient had an immunologic
      reaction or experienced with significant pain. CONCLUSIONS: Therefore, an
      artificial dermis may be an alterative to a split-thickness skin graft for
      patients with oral mucosal defects after removal of premalignant lesions.

PMID- 18050288
TI  - No mortality after 150 consecutive pancreatoduodenctomies with duct-to-mucosa
      pancreaticogastrostomy.
AB  - BACKGROUND AND OBJECTIVES: The mortality rate after pancreatoduodenectomy (PD)
      remains 0-5% at major surgical centers with the major cause of operative death
      being a leak at the pancreaticojejunal anastomosis. The aim of this retrospective
      study was to evaluate the safety of duct-to-mucosa pancreaticogastrostomy (PG) at
      a single institute. METHODS: One hundred fifty consecutive patients with
      pancreato-biliary diseases undergoing duct-to-mucosa PG following PD between 1995
      and 2005 were evaluated. One hundred forty patients underwent a pylorus
      preserving PD and 10 patients underwent a conventional PD (Whipple operation).
      External drainage of pancreatic juice was performed in 77 cases. RESULTS: The
      mean operating time was 378 min and the mean blood loss was 1,640 ml. Blood
      transfusion was not required in 97 patients (65%). The morbidity rate was 50%
      (75/150), but the mortality rate was 0%. Pancreatic fistulae occurred in 11
      patients (7%). Gender, age, operative procedure, portal vein resection, external
      drainage of the pancreatic juice, operative time, blood loss and blood
      transfusion did not affect the rate of pancreatic fistula. The rate of pancreatic
      fistulae tended to be lower in pancreatic carcinoma (3%) than non-pancreatic
      carcinoma (11%). CONCLUSIONS: Duct-to-mucosa PG is a safe procedure for
      reconstruction following PD.

PMID- 18050289
TI  - Clinical outcome of parosteal osteosarcoma.
AB  - BACKGROUND: Parosteal osteosarcoma is a rare type of osteosarcoma with distinct
      characteristics. Clinical outcome of 21 patients was analyzed to assess the
      predictive relevance of surgical margin, intramedullary tumor extension and
      histologic grade. METHODS: There were 5 mens and 16 womens with an average age of
      26 years. Average follow-up was 9.1 years (range 2.5-22.1). Most common sites
      were distal femur (15) and proximal humerus (2). No patient presented with
      metastasis. Surgical margin was wide in 13 and marginal in 8. Intramedullary
      extension was seen in 10 patients (48%). Focal high-grade 2 and 3 tumors were
      seen in 11 (52%) and 3 (14%) patients respectively. RESULTS: Twenty patients
      (95%) were alive without disease. Two (10%) had relapse, one with local
      recurrence and another with local recurrence and lung metastasis. Of eight
      marginal procedures performed, 2 turned out to have histologically tumor-positive
      margins, both of whom later developed relapses. All patients with histologically
      negative margins remained disease-free. Presence of intramedullary extension and
      focal high-grade tumor was not significantly associated with relapse.
      CONCLUSIONS: A marginal but histologically negative margin of excision appears
      adequate for parosteal osteosarcoma. However, long-term follow-up is warranted
      for monitoring of rare incidences of local recurrences or distant metastases.

PMID- 18050290
TI  - Management of carcinoma of the gallbladder: a single-institution experience in 16
      years.
AB  - BACKGROUND: Radical surgery is the only curative treatment for carcinoma of
      gallbladder. This study aimed to evaluate the outcome of patients with carcinoma
      of gallbladder managed in a single institution over 16 years. METHODS: From April
      1988 to November 2003, 86 patients (29 males, 57 females) were diagnosed to have
      carcinoma of gallbladder. Tumor staging, treatment modalities and clinical
      outcome of these patients were evaluated. Thirty-two patients (37%) had early
      stage (TNM stage I or II) disease whereas 54 patients (63%) had advanced stage
      (TNM stage III or IV) disease. Curative treatment by surgical resection was
      performed in 23 patients (27%). RESULTS: Overall survival was significantly
      better in patients with curative treatment (1-year: 85%; 2-year: 63%; 3-year:
      55%) than those with palliative treatment (1-year: 11%; 2-year: 3%; 3-year: 0%; P
      < 0.01). Using Cox regression model, curative treatment was the only independent
      prognostic factor affecting overall survival of patients with carcinoma of
      gallbladder. A significantly better survival was associated with curative
      treatment compared with palliative treatment in patients with incidental
      gallbladder cancer. The median survival was 33.9 months for the curative
      treatment group versus 3 months for the palliative treatment group (P = 0.0001).
      CONCLUSION: Favorable survival outcome can be achieved in patients with carcinoma
      of gallbladder after curative resection.

PMID- 18050291
TI  - Cytoreduction of the small bowel surfaces.

PMID- 18050292
TI  - Adjuvant therapy for pancreatic cancer: a review.
AB  - Pancreatic cancer is uniformly fatal unless it can be surgically resected.
      Survival rates for the 15% to 20% of patients who have resectable disease,
      however, are a disappointing 10% to 30%, depending on the status of margins and
      surrounding lymph nodes. In the mid-1980s, a landmark study by the
      Gastrointestinal Tumor Study Group was the first to demonstrate a survival
      benefit from adjuvant therapy in the form of chemoradiation. Since then, several
      studies in both North America and Europe have tested the role of adjuvant
      chemotherapy or chemoradiation in pancreatic cancer, and the results have stirred
      great controversy. For this review, the evidence for adjuvant therapy in
      pancreatic cancer was examined, and the significant practice differences that
      exist between North American and European oncologists were highlighted. The
      authors investigated the results from the European Study Group for Pancreatic
      Cancer-1 trial and the reasons why that study has served to reinforce rather than
      resolve these trans-Atlantic differences. They also reviewed preliminary data
      from more recent adjuvant trials and explored the possible benefits of a
      neoadjuvant approach.

PMID- 18050293
TI  - Treatment failure after primary and salvage therapy for prostate cancer.

PMID- 18050294
TI  - Treatment failure after primary and salvage therapy for prostate cancer:
      likelihood, patterns of care, and outcomes.
AB  - BACKGROUND: The authors report the likelihood of treatment failure and the
      outcomes after salvage therapy among men with prostate cancer who initially
      either received external-beam radiation therapy (EBRT) or underwent radical
      prostatectomy (RP). METHODS: Using a national disease registry, the Cancer of the
      Prostate Strategic Urological Research Endeavor (CaPSURE) database, 5277 men with
      prostate cancer were identified who initially either underwent RP (4342 men) or
      received EBRT (935 men). Outcomes after disease recurrence and subsequent salvage
      therapy were assessed. RESULTS.: Recurrent disease developed in 1590 men (30%),
      including 1003 patients (23%) in the RP group and 587 patients (63%) in the EBRT
      group, at a mean of 34 months and 38 months, respectively (P= .003). Patients who
      had recurrent disease had greater rates of overall death (19% vs 3%; P< .01) and
      bone metastases (15% vs 1%; P< .01). Data after salvage therapy were available
      for 1050 patients (620 men in the RP group and 430 men in the EBRT group).
      Androgen-deprivation therapy (ADT) was the most common salvage treatment in both
      groups. Overall, 420 men in the RP group (68%) and 319 men in the EBRT group
      (74%) failed salvage therapy at mean of 43.6 months and 43.8 months, respectively
      (P= .95). These patients had a greater overall death rate than the 311 patients
      who did not fail salvage therapy (24.8% vs 6.9%, respectively; P< .001). No
      survival benefit in terms of prostate cancer-related death (P= .91) was
      identified with any particular combination of primary and salvage therapy.
      CONCLUSIONS: Disease recurrence developed in 30% of patients who were treated for
      prostate cancer, and ADT was the most common salvage therapy used. Patients who
      failed salvage therapy had worse overall survival, and no survival benefit was
      noted for any particular combination of primary and salvage therapy.

PMID- 18050295
TI  - Active Crohn's disease and ulcerative colitis can be specifically diagnosed and
      monitored based on the biostructure of the fecal flora.
AB  - BACKGROUND: The intestinal microflora is important in the pathogenesis of
      inflammatory bowel disease (IBD). The impact of its spatial organization on
      health and disease is unknown. METHODS: We investigated sections of paraffin
      embedded punched fecal cylinders. Fluctuations in spatial distribution of 11
      bacterial groups were monitored in healthy subjects (n = 32), patients with IBD
      (n = 204), and other gastrointestinal diseases (n = 186) using fluorescence in
      situ hybridization (FISH). RESULTS: The microbial structure differed in patients
      with Crohn's disease (CD), ulcerative colitis (UC), and healthy and disease
      controls. The profiles of CD and UC were distinctly opposite in 6 of 11 FISH
      probes used. Most prominent were a depletion of Faecalibacterium prausnitzii
      (Fprau<1 x 10(9)/mL) with a normal leukocyte count in CD and a massive increase
      of leukocytes in the fecal-mucus transition zone (>30 leukocytes/10(4) microm(2))
      with high Fprau in patients with UC. These 2 features alone enabled the
      recognition of active CD (Crohn's Disease Activity Index [CDAI] >150) or UC
      (Clinical Activity Index [CAI] >3) with 79%/80% sensitivity and 98%/100%
      specificity. The mismatch in the sensitivity was mainly due to overlap between
      single IBD entities, and the specificity was exclusively due to the similarity of
      Crohn's and celiac disease. When inflammatory bowel disease (IBD) patients were
      pooled the sensitivity was 100% for severe disease, 84% for moderate activity,
      72% for IBD with < or =12 months remission, and 24% for IBD with >12 months
      remission. CONCLUSIONS: The fecal flora is highly structured and spatially
      organized. Diagnosing IBD and monitoring disease activity can be performed based
      on analysis of punched fecal cylinders independent from the patient's complaints.

PMID- 18050296
TI  - Steroid-refractory ulcerative colitis: predictive factors of response to
      cyclosporine and validation in an independent cohort.
AB  - BACKGROUND: One-third of patients with steroid-refractory ulcerative colitis (UC)
      do not respond to cyclosporine and require colectomy. Since alternative
      pharmacological treatments for this condition are available, it is pertinent to
      identify factors that predict response. The objective of this study was to
      determine predictive factors of response prior to cyclosporine administration,
      with validation in an independent cohort. METHODS: The 2 cohorts of patients were
      identified from prospectively established databases. All patients had received 1
      mg/kg/day prednisolone or equivalent for at least 5 days before cyclosporine. The
      efficacy measure was need of early surgery (within 3 months). RESULTS: From 1998
      to 2005, 34 patients were treated in 1 institution (derivation cohort) and 38
      patients in the second institution (validation cohort). Eleven patients in the
      derivation cohort and 9 patients in the validation cohort underwent early
      colectomy. Univariate analysis in the derivation cohort demonstrated a
      significant association of colectomy with C-reactive protein (P = 0.012) and the
      Ho index before initiation of cyclosporine (P = 0.013). Regression analysis
      showed that only the Ho index (P = 0.011) had an independent predictive value.
      The Ho index predicted need of colectomy, with an area under the characteristic
      receiver operating curve of 0.79 (95% confidence interval [CI], 0.59-0.99) in the
      derivation cohort and 0.74 (95% CI, 0.53-0.96) in the validation cohort. The
      cutoff point with the best sensitivity and specificity ratio was > or =5.
      CONCLUSIONS: The Ho-based predictive score is a good predictor of response to
      cyclosporine and avoidance of colectomy, and may aid in the indication of this
      treatment for management of steroid-resistant UC.

PMID- 18050297
TI  - Campylobacter and IFNgamma interact to cause a rapid loss of epithelial barrier
      integrity.
AB  - BACKGROUND: The intestinal epithelium is a single layer of polarized cells and is
      the primary barrier separating foreign antigen and underlying lymphoid tissue.
      IFNgamma alters epithelial barrier function during inflammation by disrupting
      tight cell junctions and facilitating the paracellular transport of luminal
      antigens. The aim of this work was to determine whether Campylobacter infection
      of cells exposed to IFNgamma would lead to greater disruption of cell monolayers
      and hence increased bacterial translocation. METHODS: Monolayers were polarized
      on Transwell polycarbonate membranes for 14 days and then cultured in the
      presence or absence of 100 U/mL IFNgamma. Campylobacter was added to the apical
      side of the monolayer at an MOI of 30. Transepithelial electrical resistance
      (TEER) was recorded and bacteria in the basal well counted every 2 hours. Cells
      were stained for occludin, actin, and nuclear DNA, and cell viability determined
      by measurement of apoptosis. RESULTS: In the presence of IFNgamma, TEER dropped
      significantly after 18 hours, indicating a reduction in barrier function. A
      further significant decrease was seen in the presence of both IFNgamma and
      Campylobacter, indicating a synergistic effect, and cellular morphology and
      viability were affected. Bacterial translocation across the monolayer was also
      significantly greater in the presence of IFNgamma. CONCLUSIONS: These combined
      effects indicate that Campylobacter infection concomitant with intestinal
      inflammation would result in a rapid and dramatic loss of epithelial barrier
      integrity, which may be a key event in the pathogenesis of Campylobacter-mediated
      colitis and the development of bloody diarrhea.

PMID- 18050298
TI  - Fecal S100A12 and fecal calprotectin as noninvasive markers for inflammatory
      bowel disease in children.
AB  - BACKGROUND: Fecal calprotectin is a sensitive marker for gut inflammation.
      Recently, we have established that a related protein, S100A12, is elevated in the
      feces of children with inflammatory bowel disease (IBD). This may represent a
      specific and sensitive disease marker. The objective was to investigate the
      utility of fecal S100A12, in comparison to fecal calprotectin and standard
      inflammatory markers, as a screening marker for IBD in children with
      gastrointestinal symptoms. METHODS: Stool samples were obtained from 61 children
      presenting with gastrointestinal symptoms requiring endoscopy. Fecal S100A12,
      calprotectin, and serum S100A12 levels were measured and correlated to final
      diagnosis and standard tests (ESR, CRP, platelet count, and albumin). RESULTS:
      Children diagnosed with IBD (n = 31) had elevated fecal S100A12 (median 55.2
      mg/kg) and calprotectin (median 1265 mg/kg) levels compared with the children
      without IBD (n = 30; S100A12: median 1.1 mg/kg, P < 0.0001; calprotectin: median
      30.5 mg/kg; P < 0.0001). The sensitivity and specificity of fecal S100A12 (cutoff
      10 mg/kg) for the detection of IBD were both 97%, whereas fecal calprotectin
      (cutoff 50 mg/kg) gave a sensitivity of 100% and a specificity of 67%.
      CONCLUSIONS: Both fecal markers were superior to the sensitivities and
      specificities of any standard inflammatory test. Both fecal S100A12 and
      calprotectin are sensitive markers of gastrointestinal inflammation, but fecal
      S100A12 provided exceptional specificity in distinguishing children with IBD from
      children without IBD. Fecal S100A12 is a simple, noninvasive test that can be
      used to screen and select children warranting further invasive and laborious
      procedures such as endoscopy for the investigation of their gastrointestinal
      symptoms.

PMID- 18050299
TI  - Is there a role for imatinib in inflammatory bowel disease?

PMID- 18050300
TI  - Safe use of infliximab for the treatment of fistulizing Crohn's disease during
      pregnancy within 3 months of conception.

PMID- 18050301
TI  - Analysis of metal ion-induced DNA damage, apoptosis, and necrosis in human
      (Jurkat) T-cells demonstrates Ni2+ and V3+ are more toxic than other metals:
      Al3+, Be2+, Co2+, Cr3+, Cu2+, Fe3+, Mo5+, Nb5+, Zr2+.
AB  - It remains unclear how metal released from implants affects cells of the immune
      system and, in particular, cells of the adaptive immune system, that is, T-helper
      lymphocytes. In this study, we investigated the effects of aluminum, chromium,
      cobalt, copper, iron, molybdenum, nickel, niobium, vanadium, and zirconium ions
      at concentrations from 0.05 to 5.0 mM on human CD4+ T lymphocytes. The DNA
      damage, apoptosis, necrosis, and proliferation responses of a human T-helper
      lymphocyte (Jurkat) cell line were evaluated to test our hypothesis that some
      metals will preferentially induce genotoxicity (DNA damage). Our results
      demonstrated that metal ions did not preferentially induce Jurkat T-lymphocyte
      DNA damage prior to other forms of toxicity, that is, apoptosis and/or direct
      necrosis. Nickel and vanadium induced the most DNA damage and were the most
      apoptotic metals tested, inducing >50% caspase-9 positive T cells at 0.05 mM and
      0.1 mM concentrations, respectively. Cobalt and niobium were the most toxic
      metals, inducing <50% viability at approximately 0.5 mM concentrations. Nickel
      and vanadium were the only metals to induce DNA damage at nearly the same
      concentrations that induced >50% apoptosis (i.e., <0.05 mM). All the metals
      tested induced T-cell apoptosis at a lower dose than that required to affect DNA
      damage or toxicity, implying that soluble metals released from implants may not
      be preferentially genotoxic to lymphocytes.

PMID- 18050302
TI  - Comprehensive analysis of loss of heterozygosity events in glioblastoma using the
      100K SNP mapping arrays and comparison with copy number abnormalities defined by
      BAC array comparative genomic hybridization.
AB  - We have undertaken an extensive high-resolution analysis of loss of
      heterozygosity (LOH) in 30 high grade gliomas using the Affymetrix 100K SNP
      mapping array. Only 70% of LOH events were accompanied by a copy number loss
      (CNA(loss)), and of the other 30%, the distal region of 17p preferentially showed
      copy number neutral (CNN)-associated LOH. Combined analysis of CNA(loss) and LOH
      using MergeLevels analysis software predicts whether the observed losses occurred
      on a diploid or tetraploid background. In a side-by-side comparison between SNP
      and bacterial artificial chromosome (BAC) arrays, the overall identification of
      CNAs was similar on both platforms. The resolution provided by the SNP arrays,
      however, allowed a considerably more accurate definition of breakpoints as well
      as defining small events within the cancer genomes, which could not be detected
      on BAC arrays. CNN LOH was only detected by the SNP arrays, as was ploidy
      prediction. From our analysis, therefore, it is clear that simultaneously
      defining CNAs and CNN-LOH using the SNP platform provides a higher resolution and
      more complete analysis of the genetic events that have occurred within tumor
      cells. Our extensive analysis of SNP array data has also allowed an objective
      assessment of threshold LOH scores that can accurately predict LOH. This
      capability has important implications for interpretation of LOH events since they
      have consistently been used to localize potential tumor suppressor genes within
      the cancer genome.

PMID- 18050303
TI  - Aberrant splicing of the PTPRD gene mimics microdeletions identified at this
      locus in neuroblastomas.
AB  - Neuroblastoma (NBL), a pediatric tumor arising from precursor cells of the
      sympathetic nervous system, is characterized by numerous recurrent large-scale
      chromosomal imbalances. High resolution oligonucleotide array CGH analysis of NBL
      has previously identified microdeletions that are confined to the 5' UTR of the
      protein tyrosine phosphatase receptor D (PTPRD) gene, implicating this gene in
      the pathogenesis of these tumors. Here, we demonstrate that the 5' UTR of this
      gene, consisting of 11 noncoding exons, is also aberrantly spliced in >50% of NBL
      primary tumors and cell lines. The loss of exons from the 5' UTR region through
      aberrant splicing results in aberrant mRNA isoforms that are similar to those
      generated through microdeletions. The aberrant splicing or microdeletion of 5'
      UTR exons in such a high proportion of tumors indicates that loss of these exons
      dys-regulates the mRNA sequence. To further validate the role of PTPRD in NBL, we
      have examined the expression of this gene in normal fetal adrenal neuroblasts
      (the cell of origin of NBL) and in tumors from patients with either low stage or
      high stage disease. This gene is expressed at lower levels in high stage NBL
      tumors, particularly those with amplification of MYCN, relative to low stage
      tumors or normal fetal adrenal neuroblasts, consistent with the possibility that
      loss of the 5' UTR exons have destabilized the mRNA.

PMID- 18050304
TI  - A new type of MAML2 fusion in mucoepidermoid carcinoma.
AB  - The present study reports for the first time a CRTC3-MAML2 fusion gene in a
      mucoepidermoid carcinoma, as determined by RT-PCR and sequencing. We screened a
      total of 67 formalin-fixed, paraffin-embedded mucoepidermoid carcinomas for the
      presence of chimeric genes. In one of these samples, a CRTC3-MAML2 fusion gene
      was detected. Thus, this report demonstrates the existence of a fusion of MAML2
      with CREB regulated transcriptional coactivator CRTC3 additional to the already
      known fusion of MAML2 and CRTC1. Both gene fusions seem to result in an identical
      tumor phenotype and the fusion genes CRTC1-MAML2 and CRTC3-MAML2 may play a
      similar role in the development of mucoepidermoid carcinomas.

PMID- 18050305
TI  - Further characterization of the first seminoma cell line TCam-2.
AB  - Testicular germ cell tumors of adolescents and adults (TGCTs) can be classified
      into seminomatous and nonseminomatous tumors. Various nonseminomatous cell lines,
      predominantly embryonal carcinoma, have been established and proven to be
      valuable for pathobiological and clinical studies. So far, no cell lines have
      been derived from seminoma which constitutes more than 50% of invasive TGCTs.
      Such a cell line is essential for experimental investigation of biological
      characteristics of the cell of origin of TGCTs, i.e., carcinoma in situ of the
      testis, which shows characteristics of a seminoma cell. Before a cell line can be
      used as model, it must be verified regarding its origin and characteristics.
      Therefore, a multidisciplinary approach was undertaken on TCam-2 cells,
      supposedly the first seminoma cell line. Fluorescence in situ hybridization,
      array comparative genomic hybridization, and spectral karyotyping demonstrated an
      aneuploid DNA content, with gain of 12p, characteristic for TGCTs. Genome wide
      mRNA and microRNA expression profiling supported the seminoma origin, in line
      with the biallelic expression of imprinted genes IGF2/H19 and associated
      demethylation of the imprinting control region. Moreover, the presence of
      specific markers, demonstrated by immunohistochemistry, including (wild type)
      KIT, stem cell factor, placental alkaline phosphatase, OCT3/4 (also demonstrated
      by a specific Q-PCR) and NANOG, and the absence of CD30, SSX2-4, and SOX2,
      confirms that TCam-2 is a seminoma cell line. Although mutations in oncogenes and
      tumor suppressor genes are rather rare in TGCTs, TCam-2 had a mutated BRAF gene
      (V600E), which likely explains the fact that these cells could be propagated in
      vitro. In conclusion, TCam-2 is the first well-characterized seminoma-derived
      cell line, with an exceptional mutation, rarely found in TGCTs.

PMID- 18050306
TI  - VGluT2 expression in painful Achilles and patellar tendinosis: evidence of local
      glutamate release by tenocytes.
AB  - The pathogenesis of chronic tendinopathy is unclear. We have previously measured
      high intratendinous levels of glutamate in patients with tendinosis, suggesting
      potential roles of glutamate in the modulation of pain, vascular function, and
      degenerative changes including apoptosis of tenocytes. However, the origin of
      free glutamate found in tendon tissue is completely unknown. Surgical biopsies of
      pain-free normal tendons and tendinosis tendons (Achilles and patellar) were
      examined immunohistochemically using antibodies against vesicular glutamate
      transporters (VGluT1 and VGluT2), as indirect markers of glutamate release. In
      situ hybridization for VGluT2 mRNA was also conducted. Specific immunoreactions
      for VGluT2, but not VGluT1, could be consistently detected in tenocytes. However,
      there were interindividual variations in the levels of immunoreactivity. The
      level of immunoreaction for VGluT2 was higher in tendinosis tendons compared to
      normal tendons (p < 0.05). In situ hybridization of VGluT2 demonstrated that mRNA
      was localized in a similar pattern as the protein, with marked expression by
      certain tenocytes, particularly those showing abnormal appearances. Reactivity
      for VGluT1 and -2 was absent from nerves and vessel structures in both normal and
      painful tendons. The current data demonstrate that tenocytes may be involved in
      the regulation of extracellular glutamate levels in tendons. Specifically, the
      observations suggest that free glutamate may be locally produced and released by
      tenocytes, rather than by peripheral neurons. Excessive free glutamate is
      expected to impact a variety of autocrine and paracrine functions important in
      the development of tendinosis, including tenocyte proliferation and apoptosis,
      extracellular matrix metabolism, nociception, and blood flow.

PMID- 18050307
TI  - Assessment of a goat model of posterolateral knee instability.
AB  - The development of an in vivo animal model of posterolateral knee instability is
      desired for devising effective interventions for this injury. Sequential
      sectioning of the popliteus tendon, lateral collateral ligament, and lateral
      capsule was done in cadaveric goat knees to create knee joint instability,
      followed by in vivo studies (Studies 1 and 2) of 7 and 3 months duration,
      respectively. In Study 1, the popliteus tendon and lateral collateral ligament
      were sectioned; in Study 2, these structures as well as the lateral joint capsule
      were sectioned. Biomechanical testing and histological assessments were done to
      determine the severity of the instability and the morphological changes.
      Sectioning the lateral collateral ligament and popliteus tendon (Study 1)
      resulted in a significant increase in varus instability at 90 degrees .
      Sectioning the lateral collateral ligament, popliteus tendon, and lateral capsule
      (Study 2) resulted in significant varus instability at 30 degrees , 60 degrees ,
      and 90 degrees , and significant internal-external rotation at 60 degrees and 90
      degrees ; however, the lesions of osteoarthritis in the operated knees were
      similar to those in unoperated control knees. This study confirms that
      posterolateral knee instability can be created in a goat model, but we were
      unable to demonstrate lesions of osteoarthritis that were of sufficient severity
      to allow evaluation of disease reduction in future intervention procedures.
      Future studies will determine if further manipulation of the model results in
      sufficient morphological changes to allow its use in the assessment of
      intervention strategies.

PMID- 18050308
TI  - Prevention of strain-related osteopenia in aseptic loosening of hip prostheses
      using perioperative bisphosphonate.
AB  - The hypothesis tested in this study was that perioperative administration of the
      bisphosphonate zoledronate will reduce strain protection-related calcar
      osteopenia and maintain functional integration of the femoral component in an
      ovine hemiarthroplasty model. Twelve sheep received a unilateral cemented
      hemiarthroplasty where six animals were given nine intravenous infusions of
      zoledronate (10 microg/kg) pre-, peri-, and postsurgery over 8 months. Control
      animals received physiological saline only. Implants remained in vivo for 9
      months. Ground reaction force (GRF) was used to assess functional loading of the
      implanted limb, bone mineral density (BMD) was quantified using dual energy X-ray
      absorptiometry (DEXA). Cortical bone area, thickness, and viable osteocytes were
      assessed histologically. No significant differences in GRF data between groups
      was identified. Results demonstrated a significant drop in BMD values in the
      control group (9.7%) when compared with the bisphosphonate-treated group (3.2%)
      (p = 0.0159). Histological results showed that cortical area, thickness, and the
      percentage of lacunae with viable osteocytes was significantly greater in the
      bisphosphonate-treated group when compared with control (p = 0.002, p = 0.001, p
      = 0.003, respectively). The administration of zoledronate reduced cortical
      osteopenia in the calcar region of the proximal femur and this therapy could be
      used as a preventive measure to combat strain protection osteopenia and its
      contribution to associated aseptic loosening in total hip replacement surgery.

PMID- 18050310
TI  - Optimizing CO2 normalizes pH and enhances chondrocyte viability during cold
      storage.
AB  - Fresh osteochondral allografts are an important treatment option for the repair
      of full-thickness articular cartilage defects. Viable chondrocytes within the
      transplanted tissue are considered important to maintaining matrix integrity. The
      purpose of this study is to determine whether an increase in pH decreases
      chondrocyte viability during cold storage and whether equilibration of Dulbecco's
      modified Eagle's medium (DMEM) in 5% CO(2) normalizes pH and increases
      chondrocyte survival during storage at 4 degrees C. Freshly isolated bovine
      articular chondrocytes cultured in alginate beads were stored for up to 5 days at
      4 degrees C or 37 degrees C in DMEM exposed to ambient air or in DMEM
      equilibrated with 5% CO(2). Chondrocyte viability was determined by flow
      cytometry. Physiologic pH was maintained when DMEM was equilibrated with 5%
      CO(2), while pH increased in ambient air. After 5 days of storage at 4 degrees C,
      chondrocyte necrosis was higher when stored in ambient air than if equilibrated
      with 5% CO(2). No decrease in chondrocyte viability was observed with storage at
      37 degrees C. In addition, chondrocyte viability in bovine cartilage
      osteochondral cores was examined after storage for 14 days at 4 degrees C in DMEM
      with and without HEPES, and with and without 5% CO(2). Under these conditions,
      the superficial layer of chondrocytes was more viable when stored in DMEM with
      HEPES or DMEM equilibrated with 5% CO(2) than when stored in DMEM in ambient air.
      This data shows that an increase in pH decreased bovine chondrocyte viability
      when refrigerated at 4 degrees C in DMEM, and that optimization of CO(2)
      normalized pH and improved chondrocyte viability during cold storage in DMEM.

PMID- 18050309
TI  - Inhibition of integrative repair of the meniscus following acute exposure to
      interleukin-1 in vitro.
AB  - Damage or loss of the meniscus is associated with progressive osteoarthritic
      degeneration of the knee joint. Injured and degenerative joints are characterized
      by elevated levels of the pro-inflammatory cytokine interleukin-1 (IL-1), which
      with prolonged exposure can induce catabolic and anti-anabolic activities that
      inhibit tissue repair. We used an in vitro model system to examine the hypotheses
      that acute exposure to IL-1 inhibits meniscal repair, and that an IL-1-mediated
      increase in matrix metalloproteinase (MMP) activity is associated with the
      inhibition of repair. Integrative tissue repair was studied between concentric
      explants of porcine medial menisci that were treated with IL-1alpha acutely (100
      pg/mL for 1 or 3 days) or chronically (100 pg/mL for entire culture duration).
      After 14 and 28 days in culture, biomechanical testing, cell viability, and
      histology were performed to assess meniscal repair. Total specific MMP activity
      in the culture media was measured using a quenched fluorescent substrate. As
      little as 1 day of IL-1 exposure significantly reduced shear strength, cell
      accumulation, and tissue repair compared to controls. IL-1 exposure for 1 or 3
      days significantly increased MMP activity that subsided by day 9. With chronic IL
      1 exposure, MMP activity remained elevated for the duration of culture and was
      negatively correlated with repair strength. Our study shows that short-term
      exposure to physiologically relevant concentrations of IL-1 significantly reduces
      meniscal repair in vitro, and thus may potentially inhibit the intrinsic repair
      response in vivo. The suppression of IL-1 or MMP expression and/or activity
      warrant investigation as potential strategies for promoting meniscal repair.

PMID- 18050311
TI  - Altered osteoclast development and function in osteopontin deficient mice.
AB  - The role of osteopontin in bone resorption was elucidated by studies of mice with
      knock out of the osteopontin gene generated by a different approach compared to
      previous models. Thus, a targeting vector with the promoter region as well as
      exons 1, 2, and 3 of the osteopontin gene was replaced by a loxP-flanked Neo-TK
      cassette, and this cassette was eliminated through transient expression of Cre
      recombinase. The recombined ES cells were used to create mice lacking expression
      of the osteopontin gene. Tissues from these mice were subjected structural and
      molecular analyses including morphometry and proteomics. The bone of the null
      mice contained no osteopontin but showed no significant alterations with regard
      to other bone proteins. The bone volume was normal in young null animals but in
      the lower metaphysis, the volume and number of osteoclasts were increased.
      Notably, the volume and length of the osteoclast ruffled border was several folds
      lower, indicating a lower resorptive capacity. The null mice did not develop the
      bone loss characteristic for osteoporosis demonstrated in old wild-type female
      animals. This quantitative study demonstrates a bone phenotype in the osteopontin
      null mice of all ages. The data provides further evidence for a role of
      osteopontin in osteoclast activity.

PMID- 18050312
TI  - The quantitative and functional relation between insulin-like growth factor-I
      (IGF) and IGF-binding proteins during human osteoarthritis.
AB  - A previous hypothesis stated that during osteoarthritis (OA) increased insulin
      like growth factor (IGF) binding proteins (IGFBPs) sequester IGFs and limit their
      access to the cell. The objective of this article was to test this by: (1)
      quantifying IGF and IGFBP-3 as well as their ratios in human OA cartilages, and
      (2) measuring the metabolic responses of diseased cartilage to IGF-I and its
      IGFBP-insensitive analogs. Knee or hip OA cartilages were staged for OA by
      histology. Cartilage slices were either extracted for assays of IGF proteins, or
      maintained intact as organ cultures. Proteoglycan (PG) metabolism +/- IGFs was
      measured by use of the (35)S-sulfate precursor. IGFBP-3 (ng/mg protein) was
      weakly correlated with OA score by regression analysis (R(2) = 0.122; p = 0.040;
      n = 35). IGF-I (ng/mg protein) was constant across all OA groups (ANOVA; p =
      .428, n = 18) and the IGF-I/IGFBP-3 ratios were > 1 in most samples. All OA
      cartilages responded to hrIGF-I by increasing PG synthesis [average 2.29-fold +/-
      0.55 (+/-SD) at saturation, n = 12] irrespective of OA score. The des (1-3) IGF-I
      analog (which lacks the three N-terminal amino acids) had similar maximal effects
      (average 2.23-fold stimulation +/- 0.71, n = 10), but it was more effective in
      two out of three samples at suboptimal doses. The effect of hrIGF-I, des (1-3)
      IGF-I, or the B-chain analog on degradation was minimal. In summary, catabolism
      was insensitive to IGF-I, and this was probably not due to IGFBPs. By contrast,
      IGF-I exerted a robust stimulation of anabolism at sufficiently high doses, even
      though IGFBPs could tone down the ligand effect at low doses.

PMID- 18050313
TI  - Craniosynostosis and maternal smoking.
AB  - BACKGROUND: Several previous studies suggested increased risk of craniosynostosis
      among infants born to women who smoked. METHODS: This study used data from the
      National Birth Defects Prevention Study, a multi-state, population-based case
      control study of infants delivered from 1997-2003. Nonmalformed, liveborn
      controls were selected randomly from birth certificates or birth hospitals. Data
      from maternal telephone interviews were available for 531 cases and 5008
      controls. RESULTS: Smoking during the first month of pregnancy was not associated
      with craniosynostosis. Smoking later in pregnancy was associated with increased
      risk, but only among mothers who smoked at least one pack/day. For example,
      during the second trimester, the odds ratio for smoking <5 cigarettes/day was 1.0
      (95% confidence interval [CI] 0.6, 1.8), but the odds ratio (OR) for smoking 15
      or more cigarettes/day was 1.6 (95% CI 0.9, 2.8), after adjustment for maternal
      age, education, race-ethnicity, sub-fertility, parity, folic acid supplement
      intake, body mass index, and study center. Among women who did not smoke,
      adjusted odds ratios suggested that secondhand smoke exposure at home, but not at
      work/school, was associated with modestly increased risk; the OR for home
      exposure was 1.3 (95% CI 0.9, 1.9). Results followed a similar pattern for some,
      but not all, specific suture types, but numbers for some groupings were small.
      CONCLUSIONS: The results suggest moderately increased risk of craniosynostosis
      among mothers who were the heaviest smokers and who continued to smoke after the
      first trimester. Results are somewhat equivocal, given that most confidence
      intervals included one.

PMID- 18050314
TI  - Diffusion-weighted imaging of the fetal brain in vivo.
AB  - A method of performing diffusion-weighted imaging (DWI) and diffusion tensor
      imaging (DTI) of the fetal brain in utero is proposed. The major difficulty of
      performing diffusion imaging in utero is the presence of motion. By modifying
      conventional single-shot spin-echo echo-planar DWI with a short repetition time
      sequence, a sequence that performs DWI and DTI within a breath-hold of the mother
      (13 sec and 18 sec, respectively) was devised. T(1) weighting caused by the use
      of short repetition times is compensated by interspersing diffusion imaging with
      additional b=0 image acquisitions. In utero fetal brain DWI and DTI were
      performed using this sequence. Quantitative analysis revealed minimal differences
      in the obtained apparent diffusion coefficient (ADC; directionally averaged ADC)
      values when using this sequence. The method can be readily implemented in a
      clinical setting and is especially useful when scanning mothers who cannot
      tolerate lengthier breath-holds.

PMID- 18050315
TI  - Intracellular water specific MR of microbead-adherent cells: HeLa cell
      intracellular water diffusion.
AB  - The (1)H MR signal arising from flowing extracellular media in a perfused,
      microbead-adherent cultured cell system can be suppressed with a slice-selective,
      spin-echo pulse sequence. The signal from intracellular water can, thus, be
      selectively monitored. Herein, this technique was combined with pulsed field
      gradients (PFGs) to quantify intracellular water diffusion in HeLa cells. The
      intracellular water MR diffusion-signal attenuation at various diffusion times
      was well described by a biophysical model that characterizes the incoherent
      displacement of intracellular water as a truncated Gaussian distribution of
      apparent diffusion coefficients (ADCs). At short diffusion times, the water
      "free" diffusion coefficient and the surface-to-volume ratio of HeLa cells were
      estimated and were, 2.0 +/- 0.3 microm(2)/ms and 0.48 +/- 0.1 microm(-1) (mean +/
      SD), respectively. At long diffusion times, the cell radius of 10.1 +/- 0.4
      microm was inferred and was consistent with that measured by optical microscopy.
      In summary: 1) intracellular water "free" diffusion in HeLa cells was rapid, two
      thirds that of pure water; and 2) the cell radius inferred from modeling the
      incoherent displacement of intracellular water by a truncated Gaussian
      distribution of ADCs was confirmed by independent optical microscopy measures.

PMID- 18050316
TI  - Varying kernel-extent gridding reconstruction for undersampled variable-density
      spirals.
AB  - Nonuniform, non-Cartesian k-space trajectories enable fast scanning with reduced
      motion and flow artifacts. In such cases, the data are usually convolved with a
      kernel and resampled onto a Cartesian grid before reconstruction. For
      trajectories such as undersampled variable-density spirals, the mainlobe width of
      the kernel for undersampled high spatial frequencies has to be larger to limit
      the amount of aliasing energy. Continuously varying the kernel extent is time
      consuming. By dividing k-space into several annuli and using appropriate mainlobe
      widths for each, the aliasing energy and noise can be reduced at the expense of
      lower resolution towards the edge of the field of view (FOV). Resolution can
      instead be preserved at the center of the FOV, which is expected to be free of
      artifacts, without any artifact reduction. The image reconstructed from each
      annulus can be deapodized separately. The method can be applied to most k-space
      trajectories used in MRI.

PMID- 18050317
TI  - Imaging periodic currents using alternating balanced steady-state free
      precession.
AB  - Existing functional brain MR imaging methods detect neuronal activity only
      indirectly via a surrogate signal such as deoxyhemoglobin concentration in the
      vascular bed of cerebral parenchyma. It has been recently proposed that neuronal
      currents may be measurable directly using MRI (ncMRI). However, limited success
      has been reported in neuronal current detection studies that used standard
      gradient or spin echo pulse sequences. The balanced steady-state free precession
      (bSSFP) pulse sequence is unique in that it can afford the highest known SNR
      efficiency and is exquisitely sensitive to perturbations in free precession
      phase. It is reported herein that when a spin phase-perturbing periodic current
      is locked to an RF pulse train, phase perturbations are accumulated across
      multiple RF excitations and the spin magnetization reaches an alternating
      balanced steady state (ABSS) that effectively amplifies the phase perturbations
      due to the current. The alternation of the ABSS signal therefore is highly
      sensitive to weak periodic currents. Current phantom experiments employing ABSS
      imaging resulted in detection of magnetic field variations as small as 0.15nT in
      scans lasting for 36 sec, which is more sensitive than using gradient-recalled
      echo imaging.

PMID- 18050319
TI  - Measurement of glycine in human brain by triple refocusing 1H-MRS in vivo at
      3.0T.
AB  - A new (1)H-MRS filtering strategy for selective measurement of glycine (Gly) in
      human brain in vivo at 3.0T is proposed. Investigation of multiple refocusing
      following a 90 degrees excitation pulse indicated that triple refocusing is most
      effective for suppression of the strongly coupled resonances of myo-inositol (mI)
      at the Gly 3.55-ppm resonance. The echo times of the triple refocusing were
      optimized, with numerical analysis of the filtering performance, as {TE(1),
      TE(2), TE(3)} = {67, 62, 69} ms. Compared with the 90 degrees -acquired mI signal
      the mI suppression ratios of the filter were 170 and 1000, in terms of peak
      amplitude and area, respectively, between 3.51 and 3.59 ppm. From LCModel
      analyses, using density-matrix calculated spectra as basis functions, the
      concentration of Gly in parieto-occipital cortex of healthy adults was estimated
      to be 0.5 +/- 0.1 mM (mean +/- SD, n = 6), with reference to creatine at 8 mM.

PMID- 18050320
TI  - High-resolution MRI of deep-seated atherosclerotic arteries using motexafin
      gadolinium.
AB  - PURPOSE: To evaluate the potential of using motexafin gadolinium (MGd) to
      characterize atherosclerotic plaques of deep-seated arteries with MRI. MATERIALS
      AND METHODS: We exposed vascular endothelial cells (EC) and smooth muscle cells
      (SMC) in vitro to varying concentrations of MGd. The fluorescence properties of
      MGd were then exploited using confocal microscopy to image exposed cells. For an
      in vivo validation study, we performed surface coil-based and intravascular coil
      based high-resolution MRI of the iliac arteries and the abdominal aorta of three
      atherosclerotic Yucatan pigs. Subsequently, MGd enhancement of the target vessel
      walls was quantitatively evaluated and MR images were correlated with histology
      of the target vessels. RESULTS: The in vitro study confirmed the
      intracellularization of MGd in both cell types and determined the optimum MGd
      dosage of 0.004 mmol/kg that produced the sufficiently high intracellular
      fluorescent intensity. The in vivo study showed a steady increase of MGd
      enhancement to approximately 25% at three hours postinjection of MGd. MRI showed
      areas of strong enhancement along the lumen boundary, which corresponded to
      fibrous tissue seen in histology. CONCLUSION: This study provides initial
      evidence that MGd may enhance MR vessel wall imaging for the characterization of
      plaque in deep-seated arteries.

PMID- 18050321
TI  - Comparison of the effects of independently-controlled end-tidal PCO(2) and PO(2)
      on blood oxygen level-dependent (BOLD) MRI.
AB  - PURPOSE: To assess the effect of changes in end-tidal partial pressure of O(2)
      (PETO(2)) on cerebrovascular reactivity (CVR) estimated from changes in blood
      oxygen level-dependent (BOLD) signal during cyclic changes in end-tidal partial
      pressure of CO(2) (PETCO(2)). MATERIALS AND METHODS: BOLD response to fixed
      cyclic step changes in PETCO(2) (range = 30.4-48.8 mmHg) and PETO(2) (range =
      100.6-444.0 mmHg) was studied in four healthy volunteers. RESULTS: The BOLD
      reactivity to PETCO(2) and PETO(2) were 0.283 (0.188-0.379) (median, range) and
      0.004 (0.003-0.006)%/mmHg, respectively, in the whole brain; 0.438 (0.382-0.614)
      vs. 0.006 (0.004-0.009)%/mmHg, respectively, in the gray matter; and 0.075 (0.065
      0.093) vs. 0.002 (0.001-0.002)%/mmHg, respectively, in the white matter.
      CONCLUSION: The BOLD reactivity to PETO(2) was much smaller than that to
      PETCO(2). However, BOLD reactivity can be significantly distorted by CO(2)
      induced changes in PETO(2). We conclude that PETO(2) should be carefully
      controlled during studies that use BOLD reactivity as an indicator of CVR.

PMID- 18050322
TI  - Functional imaging of the parotid glands using blood oxygenation level dependent
      (BOLD)-MRI at 1.5T and 3T.
AB  - PURPOSE: To evaluate the function of the parotid glands before and during
      gustatory stimulation, using an intrinsic susceptibility-weighted MRI method
      (blood oxygenation level dependent, BOLD-MRI) at 1.5T and 3T. MATERIALS AND
      METHODS: A total of 10 and 13 volunteers were investigated at 1.5T and 3T,
      respectively. Measurements were performed before and during gustatory stimulation
      using ascorbate. Circular regions of interest (ROIs) were delineated in the left
      and right parotid glands, and in the masseter muscle for comparison. The effects
      of stimulation were evaluated by calculating the difference between the
      relaxation rates, DeltaR(2)*. Baseline and stimulation were statistically
      compared (Student's t-tests), merging both parotid glands. RESULTS: The averaged
      DeltaR(2)* values prestimulation obtained in all parotid glands were stable (
      0.61 to 0.38 x 10(-3) seconds(-1)). At 3T, these values were characterized by an
      initial drop (to -2.7 x 10(-3) seconds(-1)) followed by a progressive increase
      toward the baseline. No significant difference was observed between baseline and
      parotid gland stimulation at 1.5T, neither for the masseter muscle at both field
      strengths. A considerable interindividual variability (over 76%) was noticed at
      both magnetic fields. CONCLUSION: BOLD-MRI at 3T was able to detect DeltaR(2)*
      changes in the parotid glands during gustatory stimulation, consistent with an
      increase in oxygen consumption during saliva production.

PMID- 18050323
TI  - MRI assessment of lung parenchymal motion in normal mice and transgenic mice with
      sickle cell disease.
AB  - PURPOSE: To test the feasibility of a method to quantify regional pulmonary
      parenchymal motion via nonrigid registration algorithm at small animal scales.
      MATERIALS AND METHODS: Voxel-wise displacement vector field maps were generated
      between end-inspiratory and end-expiratory coronal thoracic MR images on normal
      mice (N = 5) to analyze the magnitude and direction of parenchymal motion in the
      segmented regions. The analysis was repeated before and after short-term exposure
      to hypoxia to demonstrate the effect of hypoxia on the respiratory motion in
      transgenic (Tg) mice with sickle cell disease (SCD) (N = 4). RESULTS: Normal mice
      revealed that the right and left lungs moved symmetrically but that there was
      greater movement in the lower regions than in the upper regions. Calculated
      strain was uniform in the entire lung. In the Tg mice, the pulmonary motion
      before hypoxia was similar to that observed in the normal mice. Upon exposure to
      hypoxia, the displacement magnitude reduced and the direction of motion in some
      areas became distorted. CONCLUSION: MR quantification of pulmonary motion was
      feasible in mice and the principle that the method could detect mechanical
      abnormalities due to pathologic changes was proven. Quantification of pulmonary
      motion has the potential to lead to earlier disease diagnosis and better
      monitoring of disease treatments.

PMID- 18050324
TI  - Renal T2-weighted turbo-spin-echo imaging with BLADE at 3.0 Tesla: initial
      experience.
AB  - PURPOSE: The purpose of this study is to evaluate the feasibility and image
      quality of multishot T2-weighted (T2w) renal morphologic imaging based on the
      acquisition of rotating rectangular strips of k-space data after successive
      radiofrequency excitations (BLADE technique). MATERIALS AND METHODS: A total of 7
      healthy volunteers and 27 patients with suspected renal and renovascular diseases
      were included in this prospective intraindividual study. All exams were performed
      at 3.0T in a random order with a standard T2w turbo-spin-echo (TSE) sequence and
      with a T2w-BLADE sequence with equal spatial resolution. Phantom measurements
      were performed to measure the objective signal-to-noise ratio (SNR). Two
      radiologists rated the image sharpness, the flow signal suppression, the presence
      of artifacts, and the overall image quality of both techniques and determined
      their preferred sequence. RESULTS: The SNR did not show significant differences.
      The overall image quality was rated significantly higher for the T2w-BLADE (P <
      0.05). Equally, the presence of disturbing artifacts and the sharpness was ranked
      significantly better for T2w-BLADE than for the T2w-TSE (P < 0.05). The T2w-BLADE
      was the preferred sequence in 59% of all cases, the T2w-TSE in 9%.T2w-BLADE
      sequences seem to be superior for the depiction of the kidneys at 3.0T,
      particularly due to the decreased number of artifacts and sharper delineation of
      the organs.

PMID- 18050325
TI  - Diffusion imaging concepts for clinicians.
AB  - This review covers the fundamentals of diffusion tensor imaging. It is written
      with the clinician in mind and assumes the reader has a passing familiarity with
      magnetic resonance imaging (MRI). Topics covered include comparison of diffusion
      MRI with conventional MRI, water apparent diffusion coefficient (ADC), diffusion
      anisotropy, tract tracing, and changes of water apparent diffusion in response to
      injury. The discussion centers primarily on applications to the central nervous
      system, but examples from other tissues are included.

PMID- 18050326
TI  - Effect of hyaluronan on osteogenic differentiation of porcine bone marrow stromal
      cells in vitro.
AB  - Hyaluronan (HA) plays a predominant role in tissue morphogenesis, cell migration,
      proliferation, and cell differentiation. The aims of the present study were to
      investigate whether (i) prolonged presence of high concentration (4.0 mg/mL) 800
      KDa HA and (ii) pretreatment with HA can modify osteogenic differentiation of pig
      bone marrow stromal cells (pBMSC). Cell proliferation and mineralization were
      measured. Expression of differentiation-related genes was evaluated by means of
      real-time reverse transcription polymerase chain reaction (RT-PCR). HA increased
      cell proliferation on day 7. HA decreased the basal level of bone-related gene
      expression and increased the basal level of sox9 marginally during 7-day
      pretreatment with HA. HA increased calcium deposit on day 21. cbfa1, ALP, and
      type 1 alpha collagen (Col1) expression was increased when pBMSC were cultivated
      in osteogenic medium, whereas their expression was decreased in the presence of
      HA on day 7. On day 14, the addition of HA upregulated cbfa1 and ALP expression
      compared to osteogenic medium group; there was no significant difference in Col1
      expression. At day 21, osteocalcin (OC) expression showed 2.5-fold upregulation
      over osteogenic medium. These results suggest that exogenous HA stimulates
      endogenous HA, which together may play a synergetic role in osteogenic
      differentiation under osteoinducing conditions although gene expression was
      inhibited at the early stage.

PMID- 18050327
TI  - Rapid 3D-T(1) mapping of cartilage with variable flip angle and parallel imaging
      at 3.0T.
AB  - PURPOSE: To rapidly acquire T(1)-weighted images using a three-dimensional fast
      low angle shot (3D FLASH) sequence in combination with generalized
      autocalibrating partially parallel acquisitions (GRAPPA) and variable flip angle
      (VFA) method at 3.0T. MATERIALS AND METHODS: 3D T(1) maps of model systems
      (gadolinium [Gd] and agarose phantoms), bovine cartilage, and human subjects were
      constructed on a 3.0T clinical whole-body MR scanner. The T(1) values of model
      systems measured using the 2D inversion-recovery fast-spin-echo (IR-FSE) sequence
      were considered as a reference method to validate the rapid 3D method for
      comparison. RESULTS: The root mean square coefficient of variation percentage
      (RMS-CV%) of the median T(1) of agarose phantom across different acquisition
      methods was approximately 6.2%. The RMS-CV% of the median T(1) of bovine
      cartilage across different acquisition methods was approximately 4.1%. The RMS
      CV% of median T(1) of the cartilages among the subjects was between approximately
      7.3% to 11.1%. In our study, rapid 3D-T(1) mapping with VFA and parallel imaging
      with different acceleration factors (AFs) (AF = 1, 2, 3, and 4) seems to have no
      obvious influence on the T(1) mapping (before and after contrast agent
      administration). CONCLUSION: The preliminary results demonstrate that it is
      possible to quantify 3D-T(1) mapping of the whole knee joint (with 0.7 mm(3)
      isotropic resolution) under approximately five minutes with excellent in vivo
      reproducibility at 3.0T.

PMID- 18050328
TI  - Navigator-triggered isotropic three-dimensional magnetic resonance
      cholangiopancreatography in the diagnosis of malignant biliary obstructions:
      comparison with direct cholangiography.
AB  - PURPOSE: To compare the diagnostic accuracy of navigator-triggered isotropic
      three-dimensional (3D) MR cholangiopancreatography (MRCP) using parallel imaging
      for malignant biliary obstruction with direct cholangiography. MATERIALS AND
      METHODS: A total of 23 patients with malignant biliary obstruction underwent MRCP
      and endoscopic retrograde cholangiopancreatography (ERCP)/percutaneous
      transhepatic cholangiography (PTC). Two observers retrospectively evaluated 3D
      MRCP and ERCP/PTC and recorded the level of obstruction and extent of tumor along
      with their confidence. The quality of images and morphologic appearance of
      stricture were also evaluated by two reviewers. The results of MRCP and ERCP/PTC
      were compared with surgical and histopathological data. RESULTS: 3D-MRCP was of
      diagnostic quality and free of artifacts in all patients, whereas ERCP/PTC
      examinations failed in three patients. For the evaluation of level of
      obstruction, there was no statistical significance between 3D-MRCP and ERCP/PTC.
      3D-MRCP was superior to ERCP/PTC in the assessment of anatomical extent of hilar
      bile duct involvement, but did not show statistical significance. The accuracy of
      3D-MRCP in determining tumoral extent of hilar cancer was higher than that of
      ERCP/PTC, but it was not statistically significant. The image quality of 3D-MRCP
      was superior to ERCP/PTC. There was good agreement between morphologic appearance
      at MRCP and those at ERCP/PTC. CONCLUSION: 3D-MRCP can accurately assess the
      level of obstruction and extent of tumor in patients with malignant biliary
      obstruction.

PMID- 18050329
TI  - Gray and white matter changes in Alzheimer's disease: a diffusion tensor imaging
      study.
AB  - PURPOSE: To investigate microstructural changes in cortical and white matter
      pathways in patients with Alzheimer's disease using diffusion tensor imaging
      (DTI). MATERIALS AND METHODS: Measures of mean diffusivity (MD) and fractional
      anisotropy (FA) were compared in the brains of 13 Alzheimer's disease (AD)
      patients and a group of 13 aged-matched control participants employing an
      optimized DTI technique involving a fully automated, voxel-based morphometric
      (VBM) analysis. RESULTS: After rigorous control for anatomical variation and
      confounding partial volume effects, we found significantly elevated MD measures
      within the hippocampus, amygdala, and medial temporal, parietal, and frontal lobe
      gray matter regions in the AD participants. The largest number of pixels with
      increased MD was localized bilaterally, within the posterior cingulate gyrus. The
      FA was significantly reduced within the thalamus, parietal white matter, and
      posterior limbs of the internal capsule, indicating significant involvement of
      corticothalamic and thalamocortical radiations. CONCLUSION: This study
      demonstrates that rigorous VBM analysis of DTI data can be used to investigate
      microstructural changes in cortical, subcortical, and white matter regions in AD.

PMID- 18050330
TI  - Gray matter prefrontal changes in type 2 diabetes detected using MRI.
AB  - PURPOSE: To examine the volumes of the gray and white matter both globally and
      regionally in patients diagnosed with type 2 diabetes and controls. MATERIALS AND
      METHODS: Our samples were comprised of 26 patients with type 2 diabetes, 26
      patients with diabetes and major depressive disorder, and 25 nondiabetic,
      nondepressed control subjects. All subjects were studied cross-sectionally on a
      1.5 T scanner and were recruited from medicine/diabetes clinics. Both gray and
      white matter volumes were estimated using an automated method, and the prefrontal
      areas studied included the anterior cingulate, the gyrus rectus, and the
      orbitofrontal regions. RESULTS: Patients with diabetes, both with and without
      depression, had smaller total brain gray matter volumes when compared with the
      control subjects after controlling for age, intracranial volume, and years of
      education. This group also had smaller gray matter volumes in the anterior
      cingulate and orbitofrontal regions when compared with the controls after
      additionally controlling for total gray matter volume. The depressed and
      nondepressed diabetic groups did not differ on any neuroimaging measure.
      Cerebrovascular risk factors correlated negatively with gray matter volumes.
      CONCLUSION: The findings indicate that type 2 diabetes is associated with
      specific neuroanatomical abnormalities in the prefrontal gray matter. Vascular
      disease might contribute to the findings observed in our sample. These
      observations have implications for the behavioral sequelae of diabetes.

PMID- 18050331
TI  - Stimulated-echo acquisition mode (STEAM) MRI for black-blood delayed
      hyperenhanced myocardial imaging.
AB  - PURPOSE: To develop a breathhold method for black-blood viability imaging of the
      heart that may facilitate identifying the endocardial border. MATERIALS AND
      METHODS: Three stimulated-echo acquisition mode (STEAM) images were obtained
      almost simultaneously during the same acquisition using three different
      demodulation values. Two of the three images were used to construct a black-blood
      image of the heart. The third image was a T(1)-weighted viability image that
      enabled detection of hyperintense infarcted myocardium after contrast agent
      administration. The three STEAM images were combined into one composite black
      blood viability image of the heart. The composite STEAM images were compared to
      conventional inversion-recovery (IR) delayed hyperenhanced (DHE) images in nine
      human subjects studied on a 3T MRI scanner. RESULTS: STEAM images showed black
      blood characteristics and a significant improvement in the blood-infarct signal
      difference to noise ratio (SDNR) when compared to the IR-DHE images (34 +/- 4.1
      vs. 10 +/- 2.9, mean +/- standard deviation (SD), P < 0.002). There was
      sufficient myocardium-infarct SDNR in the STEAM images to accurately delineate
      infarcted regions. The extracted infarcts demonstrated good agreement with the IR
      DHE images. CONCLUSION: The STEAM black-blood property allows for better
      delineation of the blood-infarct border, which would enhance the fast and
      accurate measurement of infarct size.

PMID- 18050332
TI  - Automatic correction of echo-planar imaging (EPI) ghosting artifacts in real-time
      interactive cardiac MRI using sensitivity encoding.
AB  - PURPOSE: To develop a method that automatically corrects ghosting artifacts due
      to echo-misalignment in interleaved gradient-echo echo-planar imaging (EPI) in
      arbitrary oblique or double-oblique scan planes. MATERIALS AND METHODS: An
      automatic ghosting correction technique was developed based on an alternating EPI
      acquisition and the phased-array ghost elimination (PAGE) reconstruction method.
      The direction of k-space traversal is alternated at every temporal frame,
      enabling lower temporal-resolution ghost-free coil sensitivity maps to be
      dynamically estimated. The proposed method was compared with conventional one
      dimensional (1D) phase correction in axial, oblique, and double-oblique scan
      planes in phantom and cardiac in vivo studies. The proposed method was also used
      in conjunction with two-fold acceleration. RESULTS: The proposed method with
      nonaccelerated acquisition provided excellent suppression of ghosting artifacts
      in all scan planes, and was substantially more effective than conventional 1D
      phase correction in oblique and double-oblique scan planes. The feasibility of
      real-time reconstruction using the proposed technique was demonstrated in a scan
      protocol with 3.1-mm spatial and 60-msec temporal resolution. CONCLUSION: The
      proposed technique with nonaccelerated acquisition provides excellent ghost
      suppression in arbitrary scan orientations without a calibration scan, and can be
      useful for real-time interactive imaging, in which scan planes are frequently
      changed with arbitrary oblique orientations.

PMID- 18050333
TI  - MRI-guided radiofrequency ablation of breast cancer: preliminary clinical
      experience.
AB  - This study was designed to demonstrate the feasibility of MRI-guided
      radiofrequency ablation (RFA) of breast cancer. A total of three women diagnosed
      with invasive ductal breast cancer were treated with percutaneous MRI-guided RFA,
      according to a treat and resect protocol, in our hospital. RFA procedures were
      performed in an open 0.5T Signa-SP imager allowing direct patient access and real
      time monitoring of the procedure. In all patients ablation was performed with a
      15-gauge insulated MRI-compatible multiple needle probe. MRI thermometry and
      contrast-enhanced postablation MRI were used to evaluate the ablation process.
      Patients underwent lumpectomy within a week of the RFA procedure. Histopathology
      confirmed successful (100%) tumor ablation in one patient, and partial tumor
      destruction (33% and 50%, respectively) in two patients. Challenges of MRI-guided
      breast RFA that need to be solved to facilitate progress of the technique toward
      clinical practice are discussed.

PMID- 18050334
TI  - Usefulness of apparent diffusion coefficient map in diagnosing prostate
      carcinoma: correlation with stepwise histopathology.
AB  - PURPOSE: To elucidate the performance of apparent diffusion coefficient (ADC) map
      in localizing prostate carcinoma (PC) using stepwise histopathology as a
      reference. MATERIALS AND METHODS: Preoperative MR images of 37 patients with PC
      who had undergone radical prostatectomy were retrospectively evaluated. First, T2
      weighted images (T2WI) alone were interpreted (T2WI reading), and then T2WI along
      with ADC map were interpreted (T2WI/ADC map reading). Sextant-based sensitivity
      and specificity, and the ratio of the detected volume to the whole tumor volume
      (% tumor volume) were compared between the two interpretations, and results were
      also correlated to Gleason's scores (GS). ADC values were correlated to
      histological grades. RESULTS: Sensitivity was significantly higher in T2WI/ADC
      map reading than in T2WI reading (71% vs. 51%), but specificity was similar (61%
      vs. 60%). By adding ADC map to T2WI, % tumor volume detected increased
      significantly in transitional zone (TZ) lesions, but not in peripheral zone (PZ)
      lesions. % tumor volume detected with T2WI/ADC map reading showed a positive
      correlation with GS of the specimens. Less differentiated PC were associated with
      lower ADC values and higher detectability. CONCLUSION: T2WI/ADC map reading was
      better than T2WI reading in PC detection and localization. This approach may be
      particularly useful for detecting TZ lesions and biologically aggressive lesions.

PMID- 18050335
TI  - In vivo glenohumeral analysis using 3D MRI models and a flexible software tool:
      feasibility and precision.
AB  - PURPOSE: To implement a PC-based morphometric analysis platform and to evaluate
      the feasibility and precision of MRI measurements of glenohumeral translation.
      MATERIALS AND METHODS: Using a vertically open 0.5T MRI scanner, the shoulders of
      10 healthy subjects were scanned in apprehension (AP) and in neutral position
      (NP), respectively. Surface models of the humeral head (HH) and the glenoid
      cavity (GC) were created from segmented MR images by three readers. Glenohumeral
      translation was determined by the projection point of the manually fitted HH
      center on the GC plane defined by the two main principal axes of the GC model.
      RESULTS: Positional precision, given as mean (extreme value at 95% confidence
      level), was 0.9 (1.8) mm for the HH center and 0.7 (1.6) mm for the GC centroid;
      angular GC precision was 1.3 degrees (2.3 degrees ) for the normal and about 4
      degrees (7 degrees ) for the anterior and superior coordinate axes. The two
      dimensional (2D) precision of the HH projection point was 1.1 (2.2) mm. A
      significant HH translation between AP and NP was found. CONCLUSION: Despite a
      limited quality of the underlying model data, our PC-based analysis platform
      allows a precise morphometric analysis of the glenohumeral joint. The software is
      easily extendable and may potentially be used for an objective evaluation of
      therapeutical measures.

PMID- 18050336
TI  - Visualization and interpretation of birth defects data using linked micromap
      plots.
AB  - BACKGROUND: Many states have implemented birth defects surveillance systems to
      monitor and disseminate information regarding birth defects. However, many of
      these states rely on tabular methods to disseminate statistical birth defects
      summaries. An innovative presentation technique for birth defect data that
      portrays the information in a joint geographical and statistical context is the
      linked micromap (LM) plot. METHODS: LM plots were generated for oral cleft data
      at two geographical resolutions-USA states and counties of Utah. The LM plots
      also included demographic and behavioral risk data. RESULTS: A LM plot for the
      USA reveals spatial patterns indicating higher oral cleft occurrence in the
      southwest and the midwest and lower occurrence in the east. The LM plot also
      indicates relationships between oral cleft occurrence and maternal smoking rates
      and the proportion of American Indians and Alaskan Natives. In particular, the
      five states with the highest oral cleft occurrence had a higher proportion of
      American Indians and Alaskan Natives. Among the 15 states with the highest oral
      cleft occurrence, nine had a smoking rate of 16% or higher while among the 15
      states with the lowest oral cleft occurrence only one state had a smoking rate
      greater than 16%. The LM plot for the state of Utah shows no clear geographic
      pattern, due perhaps to a relatively small number of cases in a limited
      geographic area. CONCLUSIONS: LM plots are effective in representing complex and
      large volume birth defects data. Integration to birth defects surveillance
      systems will improve both presentation and interpretation.

PMID- 18050337
TI  - Impact of folic acid food fortification on the birth prevalence of
      lipomyelomeningocele in Canada.
AB  - BACKGROUND: Recent studies reported no reduction in the frequency of
      lipomeningomyelocele (LMMC) in Hawaii and Nova Scotia after the implementation of
      a folic acid food fortification policy in 1998, while a marked reduction in the
      prevalence of other NTDs was observed. This study was performed to assess the
      prevalence of LMMC in Canada in relation to the timing of food fortification.
      METHODS: The study population included livebirths, stillbirths, and terminations
      of pregnancies because of fetal anomaly to women residing in seven Canadian
      provinces, from 1993 to 2002. In each province, the ascertainment of NTD cases
      relied on multiple sources, and in addition all medical charts were reviewed. The
      study period was divided into pre-, partial, and full fortification periods,
      based on results of red cell folate tests published in the literature. RESULTS: A
      total of 86 LMMC cases were recorded among approximately 1.9 million live births.
      The average birth prevalence rate was 0.05/1,000, ranging from a minimum of
      0.01/1,000 in 2002 to a maximum of 0.08/1,000 in 1999. There was statistical
      heterogeneity between years (p = .01), but no pattern compatible with a decrease
      following fortification. Comparing the full fortification period with the
      prefortification period, there was a slight but not statistically significant
      decrease in LMMC birth prevalence. CONCLUSIONS: LMMC seems to be pathogenically
      distinct from myelomeningocele and more studies are needed to understand the
      embryologic mechanisms leading to this condition, and the environmental and
      genetic factors involved in its etiology.

PMID- 18050338
TI  - Deep vertical collagen fibrils play a significant role in mechanics of articular
      cartilage.
AB  - The primary orientation of collagen fibrils alters along the cartilage depth;
      being horizontal in the superficial zone, random in the transitional zone, and
      vertical in the deep zone. Commonly used confined and unconfined (when with no
      underlying bone) testing configurations cannot capture the mechanical role of
      deep vertical fibril network. To determine this role in cartilage mechanics, an
      axisymmetric nonlinear fibril-reinforced poroelastic model of tibial cartilage
      plateaus was developed accounting for depth-dependent properties and distinct
      fibril networks with physical material properties. Both creep and relaxation
      indentation models were analyzed which results were found equivalent in the
      transient period but diverged in post-transient periods. Vertical fibrils played
      a significant role at the transient period in dramatically increasing the
      stiffness of the tissue and in protecting the solid matrix against large
      distortions and strains at the subchondral junction. This role, however,
      disappeared both with time and at loading rates slower than those expected in
      physiological activities such as walking. The vertical fibrils demonstrated a
      chevron-type deformation pattern that was further accentuated with time in creep
      loading. Damages to deep vertical collagen fibril network or their firm anchorage
      to the bone, associated with bone bruises, for example, would weaken the
      transient stiffness and place the tissue at higher risk of failure particularly
      at the deep zone.

PMID- 18050339
TI  - Dynamic and static mechanical compression affects Akt phosphorylation in porcine
      patellofemoral joint cartilage.
AB  - Protein kinase B (Akt)-dependent signaling pathways induced by mechanical loading
      have been identified in a variety of tissue. However, there is no evidence for a
      potential regulation of Akt in cartilage mechanotransduction. This study was
      conducted in order to determine whether or not the Akt in chondrocytes is
      regulated by mechanical loading. Porcine patellofemoral joints were loaded in
      compression at 500 N for 150 s either dynamically at 12 Hz or 1 Hz or statically
      using a custom-designed loading frame. Left-sided knees served as intervention,
      right-sided as unloaded control. Cartilage samples were harvested at different
      time points after mechanical loading and the phosphorylation of Akt was analyzed
      immunohistochemically. A downregulation of Akt phosphorylation was seen in
      cartilage 300 s after mechanical loading whereas Akt phosphorylation remained
      unchanged in unloaded specimens. In addition, regulation of Akt appeared to
      change with the frequency of loading, presenting different patterns in Akt
      phosphorylation with static and dynamic loading. Variations in Akt
      phosphorylation were detected through different zones of cartilage. Overall, our
      findings indicate that Akt signaling in porcine patellofemoral joint cartilage is
      dependent upon frequency of loading, cartilage zone, and the time interval
      between loading and cartilage harvest. It may be concluded that Akt plays a role
      in cartilage mechanotransduction.

PMID- 18050340
TI  - Microcomputed tomography imaging in a rat model of delayed union/non-union
      fracture.
AB  - We aimed to develop a clinically relevant delayed union/non-union fracture model
      to evaluate a cell therapy intervention repair strategy. Histology, three
      dimensional (3D) microcomputed tomography (micro-CT) imaging and mechanical
      testing were utilized to develop an analytical protocol for qualitative and
      quantitative assessment of fracture repair. An open femoral diaphyseal osteotomy,
      combined with periosteal diathermy and endosteal excision, was held in
      compression by a four pin unilateral external fixator. Three delayed union/non
      union fracture groups established at 6 weeks--(a) a control group, (b) a cell
      therapy group, and (c) a group receiving phosphate-buffered saline (PBS)
      injection alone--were examined subsequently at 8 and 14 weeks. The histological
      response was combined fibrous and cartilaginous non-unions in groups A and B with
      fibrous non-unions in group C. Mineralized callus volume/total volume percentage
      showed no statistically significant differences between groups. Endosteal
      calcified tissue volume/endosteal tissue volume, at the center of the fracture
      site, displayed statistically significant differences between 8 and 14 weeks for
      cell and PBS intervention groups but not for the control group. The percentage
      load to failure was significantly lower in the control and cell treatment groups
      than in the PBS alone group. High-resolution micro-CT imaging provides a powerful
      tool to augment characterization of repair in delayed union/non-union fractures
      together with outcomes such as histology and mechanical strength measurement.
      Accurate, nondestructive, 3D identification of mineralization progression in
      repairing fractures is enabled in the presence or absence of intervention
      strategies.

PMID- 18050341
TI  - Single-shot dual-z-shimmed sensitivity-encoded spiral-in/out imaging for
      functional MRI with reduced susceptibility artifacts.
AB  - Blood oxygenation level-dependent (BOLD) functional MRI (fMRI) can be severely
      hampered by signal loss due to susceptibility-induced static magnetic field
      (B(0)) inhomogeneities near air/tissue interfaces. A single-shot spiral-in/out
      sequence with a z-shim gradient embedded between the two acquisitions was
      previously proposed to efficiently recover the signal. However, despite promising
      results, this technique had several limitations, which are addressed here as
      follows. First, by adding a second z-shim gradient before the spiral-in
      acquisition and optimizing both z-shim gradients slice-by-slice, a significantly
      more uniform signal recovery can be achieved. Second, by acquiring a B(0) map,
      the optimal z-shim gradients can be directly, efficiently, and accurately
      determined for each subject. Third, by complementing the z-shimming approach with
      sensitivity encoding (SENSE), the in-plane spatial resolution can be increased
      and, hence, susceptibility artifacts further reduced, while maintaining a high
      temporal resolution for fMRI applications. These advantages are demonstrated in
      human functional studies.

PMID- 18050342
TI  - Displacement encoding for the measurement of cartilage deformation.
AB  - Articular cartilage is a load bearing and lubricating tissue in animal joints.
      Heterogeneous deformations arise in the structured and zonal tissue under the
      application of mechanical load. The character of these deformations is altered by
      degenerative joint disease. Here, we document an MRI-based technique for
      determining deformations throughout the volume of the tissue based on
      displacement encoding with stimulated echoes (DENSE) and a fast spin echo (FSE)
      readout. A DENSE-FSE technique was designed to image cartilage at 9.4 Tesla in a
      deformed state during the application of cyclic mechanical loading. Artifact
      elimination arising from stimulated echoes and FSE was accomplished by radio
      frequency pulse phase cycling. The error of the technique was random and was
      quantified in terms of precision as better than 0.17% strain. Heterogeneous
      deformation field patterns in axial, transverse, and shear directions were
      quantified in a single tissue explant loaded in simple uniaxial compression. The
      technique is appropriate for documenting tissue deformations during applied
      physiologically relevant stress levels and loading rates. It may also be applied
      to characterize the micromechanical strain environment in normal, diseased, or
      regenerated cartilage in response to applied mechanical loading.

PMID- 18050343
TI  - Quantitative proton spectroscopic imaging of the neurochemical profile in rat
      brain with microliter resolution at ultra-short echo times.
AB  - Proton spectroscopy allows the simultaneous quantification of a high number of
      metabolite concentrations termed the neurochemical profile. The spin echo full
      intensity acquired localization (SPECIAL) scheme with an echo time of 2.7 ms was
      used at 9.4T for excitation of a slab parallel to a home-built quadrature surface
      coil in conjunction with phase encoding in the two remaining spatial dimensions
      to yield an effective spatial resolution of 1.7 microL. The absolute
      concentrations of at least 10 metabolites were calculated from the spectra of
      individual voxels using LCModel analysis. The calculated concentrations were used
      for constructing quantitative metabolic maps of the neurochemical profile in
      normal and pathological rat brain. Summation of individual spectra was used to
      assess the neurochemical profile of unique brain regions, such as corpus
      callosum, in rat for the first time. Following focal ischemia in rat pups,
      imaging the neurochemical profile indicated increased choline groups in the
      ischemic core and increased glutamine in the penumbra, which is proposed to
      reflect glutamate excitotoxicity. We conclude that it is feasible to achieve a
      sensitivity that is sufficient for quantitative mapping of the neurochemical
      profile at microliter spatial resolution.

PMID- 18050344
TI  - 19F NMR in vivo spectroscopy reflects the effectiveness of perfusion-enhancing
      vascular modifiers for improving gemcitabine chemotherapy.
AB  - Nuclear magnetic resonance spectroscopy of fluorine-19 ((19)F NMR) has proven
      useful for evaluating kinetics of fluorinated chemotherapy drugs in tumors in
      vivo. This work investigated how three perfusion-enhancing vascular modifiers
      (BQ123, thalidomide, and Botulinum neurotoxin type A [BoNT-A]) would affect the
      chemotherapeutic efficacy of gemcitabine, a fluorinated drug widely used in human
      cancer treatment. Murine tumor growth experiments demonstrated that only BoNT-A
      showed a strong trend to enhance tumor growth inhibition by gemcitabine (1.7 days
      growth delay, P = 0.052, Student t-test). In accord with these results, (19)F NMR
      experiments showed that only BoNT-A increased significantly the uptake of
      gemcitabine in tumors (50% increase, P = 0.0008, Student t-test). Further
      experiments on gemcitabine kinetics (NMR vs time) and distribution ((19)F MRI)
      confirmed the uptake-enhancing properties of BoNT-A. The results of this study
      demonstrate that (19)F NMR can monitor modulation of the pharmacokinetics of
      fluorinated chemotherapy drugs in tumors. The results also show that (19)F NMR
      data can give a strong indication of the effectiveness of perfusion-enhancing
      vascular modifiers for improving gemcitabine chemotherapy in murine tumors. (19)F
      NMR is a promising tool for preclinical evaluation of such vascular modifiers and
      may ultimately be used in the clinic to monitor how these modifiers affect
      chemotherapy.

PMID- 18050345
TI  - Diffusion tensor metrics, T2 relaxation, and volumetry of the naturally aging
      human caudate nuclei in healthy young and middle-aged adults: possible
      implications for the neurobiology of human brain aging and disease.
AB  - In this study of a cohort of 33 young and middle-age adults (19-59 years) we
      report simultaneous measurements of normal age-related changes in the caudate
      nuclei volume, diffusion tensor metrics, and T(2) relaxation time. Both the
      absolute caudate volume and its ratio relative to the total intracranial volume
      decreased rapidly with age in both men and women (r = -0.55; P < 0.001). The
      fractional diffusion tensor anisotropy of the caudate nuclei increased with age
      in both males and females (r = 0.48; P = 0.005). The corresponding age
      correlations of the caudate axial (r = 0.17; P = 0.35), transverse (r = -0.12; P
      = 0.50), mean diffusivities (r = 0.018; P = 0.92), and T(2) relaxation times (r =
      0.194; P = 0.28) were weaker and did not reach statistical significance (P >
      0.05). Our preliminary findings warrant further studies on the older and aging
      adults and indicate that caudate diffusion tensor imaging-derived metrics can be
      used as surrogates in modeling the neuronal substrates of gray matter atrophy.

PMID- 18050346
TI  - Quantitative assessment of intervertebral disc glycosaminoglycan distribution by
      gadolinium-enhanced MRI in orthopedic patients.
AB  - Our hypothesis was that the enhanced MRI of cartilage (dGEMRIC) imaging protocol
      could be used in patients to quantify the sulfated glycosaminoglycan (sGAG) in
      intervertebral discs (IVD). To test this hypothesis, 23 patients with
      degenerative disc pathology scheduled for surgery were studied by a specific
      dGEMRIC protocol: each patient underwent two MRI scans, before and 3.5 hr after
      Gd(DTPA)2-injection of a nonconventional dose of 40 mL. Then, T(1PRE-ENH) and
      T(1POST-ENH) parametric images of the disc were obtained, from which a new index
      DeltaT(1) of the molecular status of the IVD was computed (T(1PRE-ENH) - T(1POST
      ENH)). A total of 31 tissue samples (one or two from each patient) obtained at
      herniectomy were collected and biochemically analyzed for sGAG content and used
      as the gold standard for comparison. DeltaT(1) values in correspondence to
      degenerated sectors were higher (158 +/- 36 ms) compared to normal sectors (80 +/
      13 ms). Linear regression analysis between MRI-derived and biochemistry-derived
      measurements resulted in a significant correlation (r = 0.73, P < 0.0001). The
      DeltaT(1) parametric images, calculated using the modified dGEMRIC technique,
      provided noninvasive quantitative information about sGAG content within discal
      tissue in vivo, which resulted in agreement with biochemical analysis. The
      application of this new MRI method could provide diagnostic information for
      standard treatment of lumbar discopathy and for innovative therapies of
      regenerative medicine.

PMID- 18050347
TI  - Comparison of the effectiveness of saturation pulses in the heart at 3T.
AB  - Cardiac MRI at 3T provides a means to increase the contrast-to-noise ratio (CNR)
      for first-pass perfusion MRI. However, both the static magnetic field (B(0)) and
      radio frequency (RF) field (B(1)) variations within the heart are comparatively
      higher at 3T than at 1.5T. The increased field variations can degrade the
      performance of a single rectangular saturation pulse that is conventionally used
      for magnetization preparation. The accuracy of T(1)-weighted signal measurement
      depends on the uniformity of the magnetization saturation. The purpose of this
      study was to assess the relative effectiveness of the rectangular, pulse train,
      and adiabatic composite (BIR-4) saturation pulses in the human heart at 3T. In
      volunteers, after nominal saturation, the mean residual magnetization within the
      left ventricle (LV) was different between all three pulses (0.13 +/- 0.06 vs.
      0.03 +/- 0.02 vs. 0.03 +/- 0.01, respectively; P < 0.001). Within paired groups,
      the mean residual magnetization was significantly higher for the rectangular
      pulse than for either the pulse train and BIR-4 pulses (P < 0.001), but not
      different between the pulse train and BIR-4 pulses. The performances of all three
      saturation pulses were comparatively poorer in the right ventricle (RV) than in
      the LV, respectively.

PMID- 18050348
TI  - Optimization of scan parameters in pulmonary partial pressure oxygen measurement
      by hyperpolarized 3He MRI.
AB  - The dependence of hyperpolarized (HP) (3)He T(1) on local oxygen concentration
      provides the basis for measuring the partial pressure of oxygen (pO(2)) and
      oxygen depletion rate (R) in the lungs. Precise measurements of this type are
      difficult because the oxygen effect manifests itself through a decay of signal,
      leading to noisy images at the end of the series. The depolarization caused by RF
      excitation pulses further complicates the problem. It is therefore important to
      optimize scan parameters, such as measurement timing and flip angle, to obtain
      accurate and reproducible measurements. This work presents a new single
      acquisition technique in conjunction with the multiple regression fitting method
      for data evaluation. Analytical expressions for the measurement uncertainties are
      derived. A total of four types of single-acquisition timing schemes are
      investigated; simulation shows a large uncertainty variation between these
      schemes (pO(2): 7.5-30.2%; R: 47.4-173.7%). A basic procedure for optimizing scan
      parameters is then described. A phantom experiment was conducted to verify the
      simulation results. Repeated in vivo measurements with the optimal scheme in a
      rabbit experiment showed that average variation of global mean is 6.2% for pO(2)
      and 12.0% for R, and that the average variation of percentiles (10th, 25th, 50th,
      75th, and 90th) is 8.7% for pO(2) and 19.0% for R.

PMID- 18050349
TI  - SELOVS: brain MRSI localization based on highly selective T1- and B1- insensitive
      outer-volume suppression at 3T.
AB  - In vivo, high-field MR spectroscopic imaging (MRSI) profits from signal-to-noise
      ratio (SNR) gain and increased spectral resolution. However, bandwidth
      limitations of slice-selective excitation and refocusing pulses lead to strong
      chemical-shift displacement at high field strength when using conventional MRSI
      localization based on PRESS. Consequential metabolic information, particularly of
      border regions such as cortical brain tissue, is distorted. In addition, lipid
      contamination remains a major confound. To address these problems it is proposed
      to abandon PRESS selection and rely on a novel scheme of highly selective T(1)-
      and B(1)-insensitive outer-volume suppression in combination with slice-selective
      spin-echo acquisition for brain MRSI. Multiple cycles of overlapping suppression
      slabs are applied with flip angles optimized to account for tissue-dependent T(1)
      relaxation times and band crossings. Broadband frequency modulated saturation
      pulses with polynomial phase-response are utilized in order to minimize chemical
      shift displacement. Efficacy of the outer-volume suppression sequence was
      simulated and evaluated in vitro and in vivo. Brain MRSI localization at 3T was
      significantly improved and reliable suppression of short-range lipid
      contamination enabled, leading to substantial enhancement of spectral quality,
      particularly in cortical tissue. Hence, the new method holds potential to expand
      the applicability of high-field MRSI to the entire brain.

PMID- 18050350
TI  - Improved focal liver lesion detection: comparison of single-shot spin-echo echo
      planar and superparamagnetic iron oxide (SPIO)-enhanced MRI.
AB  - PURPOSE: To prospectively compare single-shot spin-echo echo-planar imaging (SSSE
      EPI) using b = 0, 10, 150, and 400 seconds/mm(2) with standard MRI techniques
      after intravenous super paramagnetic iron oxide (SPIO) in the detection and
      characterization of focal liver lesions with focus on small (<10 mm) focal liver
      lesions. MATERIALS AND METHODS: A total of 25 patients suspected for colorectal
      liver metastases were included. Number of detected lesions was evaluated. Image
      quality was compared between SSSE-EPI sequence and post-SPIO (fat-suppressed T1
      weighted [T1w] gradient echo [GE], T2-weighted [T2w] turbo spin echo [TSE] and
      T2* GE) sequences using rank order statistic (RIDIT). Lesion characterization was
      performed for SSSE-EPI and for all remaining sequences pre- and post-SPIO.
      Reference standard comprised surgery, biopsy, and/or follow-up. RESULTS:
      Reference standard demonstrated 25 hemangiomas and 70 metastases. Best lesion
      detection respectively best image quality (P < 0.05) was achieved with SSSE-EPI
      (b = 10 seconds/mm(2)) post-SPIO T1w GE and T2w turbo spin echo. Lesion
      characterization using all sequences pre- and post-SPIO performed best for lesion
      characterization compared with SSSE-EPI. CONCLUSION: This preliminary study shows
      the potential of SSSE-EPI as a stand-alone sequence for the detection of liver
      hemangiomas and metastases when compared with SPIO-enhanced imaging. Sequences
      pre- and post-SPIO are needed for qualitative lesion characterization.

PMID- 18050351
TI  - Anterior cruciate ligament volume: analysis of gender differences.
AB  - In this study, gender differences in the anterior cruciate ligament (ACL) were
      assessed with high resolution MRI. Using a quadrature extremity coil at 1.5T,
      volumes of the separate bundles of the ACL (anteromedial [AMB] and posterolateral
      [PLB]) were measured with shaded surface three-dimensional (3D) reconstruction in
      63 knees (33 male, 30 female). Bundle volumes were measured from consecutive fat
      suppressed fast spin-echo proton-density coronal MR images and intraobserver
      reproducibility was recorded. The data were divided into subgroups based on
      gender, age, height, weight, and body mass index (BMI) for statistical analysis.
      Results of the study revealed the mean ACL volume to be significantly different
      for males (1.07 cc) and females (0.77 cc) (P = 0.0025), yet when adjusting for
      body height differences, these were no longer significantly different. Mean AMB
      volume was smaller than the PLB volume for females (0.33 cc vs. 0.44 cc; P <
      0.0001) and males (0.49 cc vs. 0.58 cc; P < 0.0001). Correlation coefficients
      were highest for height (r = 0.597) and weight (r = 0.5371) and regression
      analysis revealed height to be the most significant factor affecting ACL volume.
      Intraobserver measurements were reproducible (r = 0.90). From this data, we
      conclude that gender differences in ACL volume are present, but may be accounted
      for by height differences between males and females.

PMID- 18050352
TI  - Evaluation of manual and automatic segmentation of the mouse heart from CINE MR
      images.
AB  - PURPOSE: To compare global functional parameters determined from a stack of
      cinematographic MR images of mouse heart by a manual segmentation and an
      automatic segmentation algorithm. MATERIALS AND METHODS: The manual and automatic
      segmentation results of 22 mouse hearts were compared. The automatic segmentation
      was based on propagation of a minimum cost algorithm in polar space starting from
      manually drawn contours in one heart phase. Intra- and interobserver variability
      as well as validity of the automatic segmentation was determined. To test the
      reproducibility of the algorithm the variability was calculated from the intra-
      and interobserver input. RESULTS: The mean time of segmentation for one dataset
      was around 10 minutes and approximately 2.5 hours for automatic and manual
      segmentation, respectively. There were no significant differences between the
      automatic and the manual segmentation except for the end systolic epicardial
      volume. The automatically derived volumes correlated well with the manually
      derived volumes (R(2) = 0.90); left ventricular mass with and without papillary
      muscle showed a correlation R(2) of 0.74 and 0.76, respectively. The manual
      intraobserver variability was superior to the interobserver variability and the
      variability of the automatic segmentation, while the manual interobserver
      variability was comparable to the variability of the automatic segmentation. The
      automatic segmentation algorithm reduced the bias of the intra- and interobserver
      variability. CONCLUSION: We conclude that automatic segmentation of the mouse
      heart provides a fast and valid alternative to manual segmentation of the mouse
      heart.

PMID- 18050353
TI  - Assessment of pulmonary perfusion in a single shot using SEEPAGE.
AB  - PURPOSE: To present a single-shot perfusion imaging sequence that does not
      require contrast agents or a subtraction of a tag and a control image to create
      the perfusion-weighted contrast. The proposed method is based on SEEPAGE.
      MATERIALS AND METHODS: Experiments with healthy volunteers were performed to
      qualitatively and quantitatively obtain pulmonary perfusion values in coronal as
      well as sagittal orientation. In addition, a first experiment with a lung cancer
      patient was performed to explore the potentials of SEEPAGE in a clinical
      application. RESULTS: All experiments clearly showed a perfusion-weighted
      contrast, providing clinical quality images with high spatial resolution. The
      quantified perfusion rates were consistent in the different imaging orientations
      and covered the interval of 1.00-4.00 mL/min/mL. In addition, the gravitational
      dependence of pulmonary perfusion, the influence of adiabatic pulse duration on
      signal intensity, and the tracer saturation effect were examined. In the patient
      examination the presented technique provided additional information of the lung
      deficiency compared to a conventional anatomical image. CONCLUSION: SEEPAGE has
      proved to be a robust and reproducible technique for obtaining perfusion-weighted
      images in a single measurement and for quantifying pulmonary perfusion using an
      additional reference scan. Furthermore, the proposed method shows promise for
      future clinical application.

PMID- 18050354
TI  - Renal artery stenosis: extracting quantitative parameters with a mathematical
      model fitted to magnetic resonance blood flow data.
AB  - PURPOSE: To investigate the feasibility of quantitative parameter extraction from
      a mathematical model fitted to renal artery magnetic resonance flow data.
      MATERIAL AND METHODS: A total of 16 subjects, eight patients, and eight normal
      controls, were examined with cine phase-contrast velocity measurements, and blood
      flow data from the aorta and both renal arteries were extracted by means of
      contour detection. A mathematical model with eight parameters describing the
      time, duration, and amplitude of the systolic acceleration and the diastolic
      deceleration was fitted to the aorta and renal artery blood flow data from each
      subject. The curve fitting was evaluated with R(2) values. Statistical analysis
      was performed with unpaired Wilcoxon tests and stepwise logistic regression.
      RESULTS: A total of three data sets out of 48 yielded R(2) values below 0.80 and
      were considered unreliable for parameter estimation. Basal flow was
      significantly, and systolic peak amplitude almost significantly, lower in
      stenotic arteries. Logistic regression indicated that two parameters describing
      basal flow and the duration of acceleration can accurately predict stenosis.
      CONCLUSION: The results suggest that it is technically feasible to fit a
      mathematical model to renal blood flow data, extracting quantitative parameters
      that may prove useful for quantification and diagnosis of renal artery stenosis.

PMID- 18050355
TI  - Effects of doubling and tripling the spatial resolution in standard 3D contrast
      enhanced magnetic resonance angiography of carotid artery disease.
AB  - PURPOSE: To determine whether three-dimensional (3D) contrast-enhanced MR
      angiography (CE-MRA) of carotid artery disease may be more effective when
      performed at double or triple the spatial resolution of the present common
      clinical standard at 1.5T. MATERIALS AND METHODS: A total of 110 consecutive
      patients with suspected carotid artery disease were imaged with elliptical
      centric 3D CE-MRA. The total acquisition time was increased from the standard
      clinical protocol of 21 seconds up to 60 seconds in 10-second steps, with
      corresponding voxel volume reductions from 0.95 mm(3) down to 0.35 mm(3).
      Quantitative and blinded qualitative measurements were then performed to
      determine the preferred imaging time. RESULTS: In patients with significant
      stenosis, the 40-second acquisition with 0.53-mm(3) voxels produced significantly
      sharper images of the carotid bifurcation than the 21-second standard using 0.95
      mm(3) voxels, but did not have a significant effect in patients without disease.
      CONCLUSION: In patients with carotid artery stenosis, decreasing the voxel volume
      to 0.5 mm(3) by increasing the scan time from 21 to 40 seconds resulted in
      sharper depiction of the carotid stenosis. Further decreases in voxel volume, by
      extending the acquisition time further, did not improve the vessel depiction due
      to both signal-to-noise ratio (SNR) and sharpness losses.

PMID- 18050356
TI  - Bony impingement affects range of motion after total hip arthroplasty: A subject
      specific approach.
AB  - Hip range of motion after total hip arthroplasty has been shown to be dependent
      on prosthetic design and component placement. We hypothesized that bony anatomy
      would significantly affect range of motion. Computer models of a current
      generation hip arthroplasty design were virtually implanted in a model of pelvis
      and femur in various orientations ranging from 35 degrees to 55 degrees cup
      abduction, 0 degrees to 30 degrees cup anteversion, and 0 degrees to 30 degrees
      femoral anteversion. Four head sizes ranging from 22.2 to 32 mm and two neck
      sizes ranging from 10-mm and 12-mm diameter were tested. Range of motion was
      recorded as maximum flexion-extension, abduction-adduction, and axial rotation of
      the femur before any contact between prosthetic components or bone was detected.
      Bony impingement preceded component impingement in about 44% of all conditions
      tested, ranging from 66% in adduction to 22% in extension. Range of motion
      increased as head size increased. However, increasing head size also increased
      the propensity for bony impingement, which tended to reduce the beneficial effect
      of increased head size on range of motion. Reducing neck diameter had a greater
      effect on prosthetic impingement (mean, 3.5 degrees increase in range of motion)
      compared to bone impingement (mean, 1.9 degrees ). This model allowed for a
      clinically relevant assessment of range of motion after total hip arthroplasty
      and may also be used with patient-specific geometry [such as that obtained from
      preoperative computed tomography (CT) scans] for more accurate preoperative
      planning.

PMID- 18050357
TI  - Lymphocytic vacuolization in sialic acid storage disease.

PMID- 18050358
TI  - Na+/Ca2+-exchanger-mediated Mn2+-enhanced (1)H2O MRI in hypoxic, perfused rat
      myocardium.
AB  - Paramagnetic Mn2+ has emerged in the search for non-invasive magnetic resonance
      imaging (MRI) techniques to monitor Ca2+ in diagnostic and prognostic
      cardiovascular disease tests because it both alters MRI contrast and behaves as a
      Ca2+ 'surrogate' in vivo. However, the reliance on macroscopically averaged
      measurements to infer microscopic processes constitutes a major limitation of
      MRI. This investigation circumvents this limitation and contributes an MRI-based
      myocardial Ca2+-transporter assay, which probes the Na+/Ca2+-exchanger
      involvement in Mn2+ (and presumably Ca2+) transport by virtue of its response to
      pharmacological inhibition. In the model employed herein, ex vivo arrested rat
      hearts underwent normoxia and then hypoxia while a constant (hyperkalemic)
      perfusion minimized flow (and uncontrolled Ca2+-channel) contributions to Mn2+
      enhanced MRI measurements. The results (i) demonstrate that Mn2+ (and presumably
      Ca2+) accumulates via Na+/Ca2+-exchanger-mediated transport during hyperkalemic
      hypoxia and further, (ii) implicate hypo-perfusion (rather than the diminished
      participation of an isolated sarcolemmal Ca2+-transporter) as the mechanism that
      underlies the reported reductions of Mn2+ accumulation (relative to healthy
      myocardium) subsequent to myocardial insults in MRI studies. Although myriad
      studies have employed Mn2+-enhanced MRI in myocardial investigations, this
      appears to be the first attempt to assay the Na+/Ca2+-exchanger with MRI under
      highly circumscribed conditions. MRI-based Ca2+)transporter assays, such as the
      Na+/Ca2+-exchanger assay utilized here, will inevitably impact disciplines in the
      medical sciences and beyond.

PMID- 18050359
TI  - Can we differentiate true white matter fibers from pseudofibers inside a brain
      abscess cavity using geometrical diffusion tensor imaging metrics?
AB  - High fractional anisotropy (FA) usually reflects the orientation and integrity of
      white matter (WM) fibers. Other regions of increased FA have been described, such
      as brain abscesses, developing cortex, and areas of hemorrhage. It may not be
      possible to differentiate true fibers from the pseudofibers found inside an
      abscess cavity on the basis of FA and mean diffusivity (MD). The aim of this
      study was to differentiate true WM fibers from pseudo WM tracts inside the
      abscess cavity using geometrical diffusion tensor imaging metrics [linear
      anisotropy (CL), planar anisotropy (CP), and spherical anisotropy (CS)].
      Diffusion tensor imaging was performed in 42 patients with brain abscess and 10
      age/sex-matched controls. Automated segmentation using Java-based software
      divided the abscess cavity into two sub-regions with FA < 0.20 and FA > or =
      0.20. Quantitation was carried out on the sub-regions of the abscess cavity with
      FA > or = 0.20. In healthy controls, regions of interest were placed on the
      corpus callosum, posterior limb of the internal capsule, and periventricular and
      subcortical WM. Significantly increased CP values were observed inside the
      abscess cavity compared with various normal WM regions. Significantly increased
      FA and CL values were observed in the abscess cavity compared with subcortical WM
      only. However decreased FA and CL values were observed in the cavity compared
      with the corpus callosum, posterior limb of the internal capsule, and
      periventricular WM. The 95% confidence intervals of means for the abscess cavity
      were well separated from those for WM in the case of CL and CP; however, they
      overlapped in the case of FA, MD, and CS. High CP with low CL inside the abscess
      cavity suggests that the shape of the diffusion tensor is predominantly planar,
      whereas it is linear in WM tracts. These geometrical indices may have advantages
      over FA for differentiating true from pseudo WM tracts inside the abscess cavity.

PMID- 18050360
TI  - Potentially inappropriate prescribing to hospitalised patients.
AB  - PURPOSE: The objective of this study was to evaluate the prevalence of potential
      drug-drug interactions (DDIs) in hospitalised patients in correlation with
      patient's age and number of drugs prescribed and to determine the prevalence of
      inappropriate drugs prescribed to elderly patients. METHODS: Drugs prescribed
      during 1 day to all hospitalised patients at seven wards of Department of
      Medicine in University Hospital Rijeka were recorded by reviewing patient medical
      charts. Potential DDIs were evaluated using a list of potentially harmful drug
      combinations compiled from the literature. Beers criteria were used to identify
      potentially inappropriate medications in patients aged 65 years or older.
      RESULTS: The study included 225 patients that received a total of 1301 drugs.
      Twenty-two percent of the patients receiving drug therapy were prescribed drug
      combinations that are potentially harmful. The most common potentially harmful
      drug combination was an ACE inhibitor with a potassium supplement (33.9% of all
      combinations). In the multivariate analysis, age and number of drugs are
      significantly associated with potential DDIs (r = 0.8629). One quarter of elderly
      patients received a drug potentially inappropriate considering their age. The
      most commonly prescribed potentially inappropriate drug was amiodarone, followed
      by diazepam. CONCLUSION: Polypharmacy and older age have been proven to be
      important risk factors for potential drug interactions. We identified a high rate
      of prescribing potentially inappropriate medications among elders. Results of
      this study indicate that particular caution should be given when prescribing
      drugs to patients already receiving drugs and to elderly patients, considering
      the risk of drug-related problems.

PMID- 18050361
TI  - SPR identification of mild elution conditions for affinity purification of E6
      oncoprotein, using a multivariate experimental design.
AB  - The purification of "difficult" proteins for structural and functional studies
      remains a challenge. A widely used approach is their production as fusions with
      an affinity tag, so that a generic tag-based purification protocol can be
      applied. Alternatively, immuno-affinity using a protein-specific antibody allows
      purification of unmodified proteins in a single step, if mild elution conditions
      can be identified for dissociating the complex without disrupting the folding of
      the protein. Here, we describe a quantitative structure activity relationship
      (QSAR) strategy to predict optimized elution conditions from a mathematical model
      that relates target/antibody dissociation to environmental changes. We illustrate
      the strategy with the E6 protein of the human papilloma virus (HPV) 16, a highly
      unstable protein central to HPV-induced carcinogenesis. Surface plasmon resonance
      (SPR) was used to measure the kinetics of dissociation of an E6 peptide from an
      E6-specific antibody in a set of multivariate conditions, where three
      environmental factors (pH, NaCl concentration, and temperature) were varied. The
      QSAR model indicated that dissociation is favored at pH < 5, which is detrimental
      to E6 folding, and also at pH > or = 10 if the temperature is high. We verified
      that the conclusions of the QSAR study with the peptide were valid for the
      scFv1F4/E6 protein complex, and that the recovered protein was capable of
      mediating p53 degradation. Finally, we demonstrated that the optimized elution
      conditions (pH 10, 35 degrees C) were adequate for purifying the recombinant E6
      protein from crude cell extracts.

PMID- 18050362
TI  - Do patients with schizophrenia receive state-of-the-art lung cancer therapy? A
      brief report.
AB  - OBJECTIVE: Patients with schizophrenia sometimes receive substandard medical
      care. This study explored such disparities among lung cancer patients with
      underlying schizophrenia. METHODS: This retrospective study focused on patients
      with pre-existing schizophrenia (or in some instances schizoaffective disorder)
      and a lung cancer diagnosis made between 1980 and 2004. 'Disparity' was defined
      as a patient's having been prescribed less aggressive therapy for a potentially
      curable cancer based on state-of-the-art treatment standards for the time and for
      the cancer stage. Qualitative methods were used to assess healthcare providers'
      decision-making. RESULTS: 29 patients were included. The median age was 59 years;
      38% were men. Twenty-three had non-small cell lung cancer and 6 small cell lung
      cancer; 17 had potentially curable cancers. Five of 17 had a 'disparity' in
      cancer care: (1) no cancer therapy was prescribed because of chronic obstructive
      pulmonary disease; (2) no cancer therapy was prescribed because of infection; (3)
      no chemotherapy was prescribed because the patient declined it; radiation was
      provided; (4) no chemotherapy was prescribed because of the patient's
      schizophrenia symptoms; radiation was administered; and (5) no surgery was
      performed because of disorientation from a lobotomy; radiation was prescribed.
      Comments from healthcare providers suggest reflection and ethical adjudication in
      decision-making. CONCLUSION: Schizophrenia was never the sole reason for no
      cancer treatment in patients with potentially curable lung cancer. This study
      provides the impetus for others to begin to assess the effect of schizophrenia on
      lung cancer management in other healthcare settings.

PMID- 18050363
TI  - The presence of high-risk chromosome aberrations in chronic lymphocytic leukaemia
      does not correlate with centrosome aberrations.
AB  - Chromosome aberrations are frequently found in B-cell chronic lymphocytic
      leukaemia (B-CLL), and specific chromosome aberrations identify poor prognostic
      subgroups. Almost all the aberrations identified in B-CLL involve loci where
      genes with a role in the regulation of centrosome duplication have been mapped.
      Centrosome aberrations have been described as a possible cause of numerical
      chromosome abnormalities in both solid and haematological tumours. However,
      little is known about the possible role of centrosome aberrations in B-CLL. To
      investigate whether centrosome aberrations do occur in B-CLL and correlate with
      cytogenetically defined prognostic subgroups, we examined a set of 64 B-CLL
      samples by immunofluorescent staining. B-CLL cases differed significantly from
      controls in the mean frequency of cells with centrosome aberrations, while no
      difference was found between subgroups with or without specific chromosome
      aberrations. Our results indicated that although centrosome aberrations were a
      common feature in B-CLL, they did not represent a reliable prognostic marker.

PMID- 18050364
TI  - Peripheral T-cell lymphomas, unspecified (or not otherwise specified): a review.
AB  - Peripheral T-cell lymphomas (PTCL) comprises a heterogeneous group of
      haematological tumours, which originate from mature T-cells, and constitute less
      than 15% of all non-Hodgkin's lymphomas (NHLs) in adults. The current WHO
      classification recognizes nine distinct clinicopathologic peripheral T-cell NHLs,
      being the 'unspecified variant' (PTCL-U) the most common subtype. These neoplasms
      often present in advanced stage at diagnosis, and most commonly have an
      aggressive clinical course requiring prompt treatment. The rarity of these
      tumours requires additional studies to better understand their biology and search
      for new therapies which may hopefully improve the dismal outcome of most
      patients. This review aims to describe the pathobiological aspects as well the
      clinical characteristics and current therapeutic strategies of the PTCLs, with
      special attention to the group of PTCL-U.

PMID- 18050365
TI  - Hepatitis A-associated macrophage activation syndrome in children with systemic
      juvenile idiopathic arthritis: report of 2 cases.
AB  - OBJECTIVE: We describe two 3-year-old patients with systemic juvenile idiopathic
      arthritis (SJIA) who developed hepatitis A-associated macrophage activation
      syndrome (MAS). One patient showed MAS as the presenting manifestation of SJIA,
      while MAS complicated SJIA during the second year of the disease course in the
      other child. Both girls presented with fever, jaundice, hepatosplenomegaly,
      neurological involvement, mucosal hemorrhage, and purpura. Cytopenias,
      hypofibrinogenemia, and hemophagocytosis confirmed the diagnosis. After
      aggressive treatment with high-dose corticosteroids and immunosuppressants one
      patient entered remission while the other one died. Hepatitis A virus may induce
      severe MAS in SJIA.

PMID- 18050366
TI  - Etanercept treatment improves longitudinal growth in prepubertal children with
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: Anti-tumor necrosis factor (TNF) therapy is known to decrease disease
      activity of juvenile idiopathic arthritis (JIA), but its effect on longitudinal
      growth in relation to puberty is not clear. We studied longitudinal growth in
      response to etanercept treatment in prepubertal and pubertal patients with JIA.
      METHODS: Out of 52 children treated with etanercept, we studied 20 prepubertal
      and 11 early/midpubertal patients adherent to treatment for at least 1 year. We
      collected data on growth and glucocorticoid medication and calculated each
      patient's height standard deviation score (SDS) in relation to the mid-parental
      height, the change of this value (DeltahSDS) from 1 to 0 and 0 to 1 year of
      treatment, and the change between the DeltahSDS values to assess growth
      improvement. RESULTS: In the prepubertal group, the relative height SDS (mean +/-
      standard error of the mean) was 1.8 +/- 0.2, 2.1 +/- 0.3, and 1.9 +/- 0.3, and in
      the pubertal group 1.1 +/- 0.4, 1.3 +/- 0.3, and 1.1 +/- 0.3 at 1, 0, and +1 year
      of treatment, respectively. The DeltahSDS before etanercept was 0.3 +/- 0.1 in
      prepubertal and 0.2 +/- 0.2 in pubertal patients. Over the first year with
      etanercept, DeltahSDS was +0.2 +/- 0.1 in prepubertal (p = 0.001 vs before
      etanercept; paired Student t-test) and +0.2 +/- 0.1 in pubertal patients (p =
      0.071). Nevertheless, most prepubertal (17/20) and pubertal (8/11) patients had
      improved growth (DeltahSDS) in response to etanercept treatment when analyzed
      individually. The need for intraarticular glucocorticoid injections was
      negatively correlated to the improved growth (p = 0.001). CONCLUSION: TNF
      inhibition with etanercept improved growth in a majority of patients with JIA.
      Our data demonstrate that growth improvement with etanercept was independent of
      the pubertal growth spurt.

PMID- 18050367
TI  - T regulatory cells are markedly diminished in diseased salivary glands of
      patients with primary Sjogren's syndrome.
AB  - OBJECTIVE: To investigate the abnormalities of T regulatory cells (Treg) in
      salivary glands and peripheral blood in patients with primary Sjogren's syndrome
      (pSS). METHODS: Levels of CD4+CD25+ high T cells of the peripheral blood of 52
      patients with pSS were measured by flow-cytometric assay. Lower lip salivary
      gland biopsies were examined by immunohistochemistry, using monoclonal mouse anti
      human antibodies [CD25, CD4, CD8, CD68, forkhead transcription factor (Foxp3)] in
      30 patients with pSS. Using real-time polymerase chain reaction, Foxp3 messenger
      RNA expression was assessed in the salivary glands and CD4+ T cells from
      peripheral blood. RESULTS: Many inflammatory cells, predominantly CD4+ and CD8+ T
      cells and macrophages, were found in salivary glands of patients with SS, but
      CD4+CD25+ Treg numbers and Foxp3 expression were markedly reduced in those biopsy
      samples. Levels of CD4+CD25+ high T cells and Foxp3 expression in peripheral
      blood of patients with pSS were significantly lower than in healthy controls.
      However, the inhibitory function of CD4+CD25+ T cells in pSS was unchanged
      compared to that of controls. Peripheral CD4+CD25+ high T cell numbers in pSS did
      not correlate with Schirmer's test and salivary flow rate, or with the presence
      or absence of anti-SSA/SSB antibodies and immunoglobulin level. CONCLUSION: The
      remarkable reduction of Treg numbers in salivary glands and reduction of
      CD4+CD25+ high T cells in peripheral blood suggests a possible role for absence
      of Treg in the pathogenesis of salivary gland destruction in pSS.

PMID- 18050368
TI  - Longterm effect of intermittent cyclical etidronate therapy on corticosteroid
      induced osteoporosis in Japanese patients with connective tissue disease: 7-year
      followup.
AB  - OBJECTIVE: To determine the efficacy and safety of intermittent cyclical
      etidronate therapy of up to 7 years for corticosteroid-induced osteoporosis.
      METHODS: One hundred two Japanese patients who originally participated in a 3
      year prospective randomized study were enrolled into an open-label followup
      study. All patients had received > 7.5 mg of prednisolone daily for at least 90
      days before entry into the original study and were randomly assigned to 2
      treatment arms: E, those receiving etidronate disodium (200 mg per day) for 2
      weeks together with 3.0 g of calcium lactate and 0.75 microg of alphacalcidol
      daily; and C, controls receiving only the latter. Endpoints included changes from
      baseline in bone mineral density (BMD) of the lumbar spine and the rate of new
      vertebral fractures. RESULTS: The mean (+/- SD) lumbar spine BMD had increased by
      5.9% +/- 8.8% (p = 0.00007) and 2.2% +/- 5.8% (p = 0.013) from baseline after 7
      years in groups E and C, respectively. This improvement in BMD in group E was
      significantly better than in group C (p = 0.02). The frequency of new vertebral
      fractures was lower in group E, resulting in reduction of the risk of such new
      fractures by 67% at year 7 (odds ratio 3.000; 95% confidence interval, 0.604
      14.90; p = 0.18). There were no severe adverse events in group E during our
      study. CONCLUSION: Our results indicate that longterm (up to 7 years)
      intermittent cyclical etidronate therapy is safe and effective for prevention and
      treatment of corticosteroid-induced osteoporosis in patients with connective
      tissue diseases.

PMID- 18050369
TI  - Diagnostic accuracy of serum procalcitonin concentrations for detecting systemic
      bacterial infection in patients with systemic autoimmune diseases.
AB  - OBJECTIVE: To examine whether serum procalcitonin (PCT) concentrations are useful
      for distinguishing bacterial infections from disease flares in patients with
      systemic autoimmune diseases. METHODS: Patients with systemic autoimmune diseases
      who were admitted to our hospitals due to either a suspected deterioration of
      their primary diseases or an infectious disease were enrolled. Serum PCT levels
      were measured in 99 serum samples of 98 patients who had elevated serum C
      reactive protein (CRP) levels; 29 samples were obtained from patients with
      bacterial infections, and 70 samples were obtained from patients with disease
      deterioration without a detectable infection. The diagnostic accuracy,
      sensitivity, and specificity for identifying a bacterial infection were estimated
      using the receiver-operating characteristic curve. Multiple logistic regression
      analysis was also done with PCT level, age, sex, steroid dose, and use of
      immunosuppressive agents. RESULTS: Serum PCT levels were higher in the bacterial
      infection group than in the disease flare group (mean +/- SD, 4.539 +/- 9.677 vs
      0.116 +/- 0.127; p < 0.0001). The diagnostic accuracy of PCT for bacterial
      infection was 0.797, sensitivity 53.3%, and specificity 97.1%. On multivariate
      analysis, the odds ratio of a PCT > or = 0.5 ng/ml was significant (OR 59.085,
      95% CI 7.705 453.088, p < 0.0001) for identifying bacterial infection.
      CONCLUSION: Elevated serum PCT levels have a good specificity for diagnosing
      bacterial infection in patients with systemic autoimmune diseases regardless of
      their dosage of oral corticosteroids and immunosuppressive agents.

PMID- 18050370
TI  - Developing classification criteria for polymyalgia rheumatica: comparison of
      views from an expert panel and wider survey.
AB  - OBJECTIVE: This report summarizes the findings from a consensus process to
      identify potential classification criteria for polymyalgia rheumatica (PMR).
      METHODS: A 3-stage hybrid consensus approach was used to develop potential PMR
      classification criteria. The first stage consisted of a facilitated meeting of 27
      international experts who anonymously rated the importance of 68 potential
      criteria. The second stage involved a meeting of the experts, who were provided
      with the results of the first round of ratings and were then asked to re-rate the
      criteria. In the third stage, the wider acceptance of the 43 criteria that
      received > 50% support at round 2 was evaluated using an extended mailed survey
      of 111 rheumatologists and 53 nonrheumatologists in the United States, Canada,
      and Northern and Western Europe. RESULTS: A total of 68 and 50 criteria were
      identified and rated in round 1 and round 2, respectively. In round 2, 43 of the
      50 items achieved at least 50% support, including 10 core criteria achieving 100%
      support. In round 3, over 70% of survey respondents agreed on the importance of 7
      core criteria. These were age >or=50 years, duration >or=2 weeks, bilateral
      shoulder and/or pelvic girdle aching, duration of morning stiffness > 45 min,
      elevated erythrocyte sedimentation rate, elevated C-reactive protein, and rapid
      steroid response (> 75% global response within 1 wk to prednisolone/prednisone 15
      20 mg daily). Among physical signs, more than 70% of survey respondents agreed on
      the importance of assessing pain and limitation of shoulder (84%) and/or hip
      (76%) on motion, but agreement was low for peripheral signs like carpal tunnel,
      tenosynovitis, and peripheral arthritis. CONCLUSION: There are differences in
      opinion as to what PMR is and how it should be treated. These findings make it
      important to develop classification criteria for PMR. The next step is to perform
      an international prospective study to evaluate the utility of candidate
      classification criteria for PMR in patients presenting with the polymyalgic
      syndrome.

PMID- 18050371
TI  - The CD40/CD40 ligand system in the skin of patients with subacute cutaneous lupus
      erythematosus.
AB  - OBJECTIVE: To investigate whether CD40 and CD40 ligand (CD40L) is expressed in
      the skin of patients with subacute cutaneous lupus erythematosus (SCLE). METHODS:
      Six female patients with SCLE were studied. Skin biopsies were obtained from
      lesional and healthy sunprotected skin. Frozen sections were stained
      immunohistochemically using monoclonal antibodies to CD4, CD40, and CD40L. As
      controls we used 5 patients with discoid LE (DLE), 5 with dermatomyositis (DM), 3
      with lichen planus (LP), and 2 with erythema multiforme (EM), as well as the
      normal-appearing skin of 5 healthy volunteers. RESULTS: The CD40 was intensely
      expressed in all SCLE, DLE, and DM lesions, and only focally in healthy
      sunprotected skin specimens. The number of CD40+ cells in SCLE dermis was lower
      than in DLE, similar to that in DM, LP and EM, and higher than in SCLE
      sunprotected skin. CD40L+ cells infiltrated the SCLE, DLE, DM, LP, and EM
      lesional dermis, and were more numerous in SCLE lesional skin than in SCLE
      healthy sunprotected skin. CONCLUSION: We showed that the CD40/CD40L system may
      represent an important pathway of induction of SCLE lesions. The expression of
      such costimulatory system in healthy sunprotected skin also may signify that its
      abnormal activation is constitutive in SCLE, as previously observed in systemic
      LE.

PMID- 18050372
TI  - Early psoriatic arthritis: the clinical spectrum.
AB  - OBJECTIVE: To characterize the clinical pattern of early psoriatic arthritis
      (PsA). METHODS: We studied 47 consecutive patients: 29 had definite PsA and 18
      had the "sine psoriasis" subset. Inclusion criteria were articular and/or
      entheseal involvement of < or =12 weeks' duration and the exclusive use, before
      enrollment, of nonsteroidal antiinflammatory drugs to control articular symptoms.
      All patients underwent clinical examination, blood tests, total-body bone
      scintigraphy, articular ultrasonography, and radiography of clinically involved
      joints and/or entheses. RESULTS: On the basis of clinical examination, early PsA
      was an oligo-enthesoarthritis in over 75% of patients studied. In contrast, the
      number of joints and/or entheses showing increased tracer uptake on bone
      scintigraphy was 3 times greater, compared to the clinical evidence (p < 0.001).
      Articular ultrasonography confirmed the inflammatory involvement of synovium
      and/or entheses in all articular sites active at time of bone scintigraphy, but
      silent at clinical examination. In addition, 7 patients showed the occurrence of
      joint and/or entheseal erosions on standard radiography. CONCLUSION: Bone
      scintigraphy yields a more accurate evaluation of entheso-articular involvement
      and distribution in patients with early PsA. Our results suggest that clinical
      oligo-enthesoarthritic presentation of early PsA might represent in most cases a
      polyarticular condition that is at increased risk for clinical progression. These
      findings have a significant influence on the clinical decision-making process in
      patients with early PsA.

PMID- 18050373
TI  - Retinol (vitamin A) and retinol-binding protein levels are decreased in
      ankylosing spondylitis: clinical and genetic analysis.
AB  - OBJECTIVE: Retinol (vitamin A) plays an important role in bone structure and
      function. Treatment with retinoids has been associated with bone abnormalities
      mimicking spondyloarthropathy and diffuse idiopathic skeletal hyperostosis. To
      determine whether retinol concentrations are altered in patients with ankylosing
      spondylitis (AS), we examined serum retinol levels in patients with AS and
      healthy controls. METHODS: Retinol was assessed using mass spectrometry, and
      retinol-binding protein levels were assessed by ELISA. Retinol levels were
      correlated with clinical disease activity indices. The CYP26 gene, which plays a
      key role in retinol metabolism, was examined to define any single-nucleotide
      polymorphisms (SNP) associations with AS. RESULTS: Retinol levels were
      significantly lower in the AS cohort than in controls (mean 2.39 +/- 0.88
      micromol/l for AS, 3.34 +/- 1.01 micromol/l for controls; p < 0.0001). Retinol
      binding protein levels were also lower in AS than controls (AS 4.65 +/- 2.10
      microg/l; controls 7.48 +/- 4.87 microg/l; p < 0.001). Serum retinol levels did
      not correlate with indices of disease activity defined serologically (C-reactive
      protein, erythrocyte sedimentation rate) or clinically (Bath AS Disease Activity
      Index, Bath AS Functional Index). Genetic analysis showed that an exonic CYP26C1
      SNP (rs11187265) is not associated with AS. CONCLUSION: The hallmark of AS is neo
      ossification. AS is associated with abnormal serum levels of retinol, a
      biochemical factor linked to pathological hyperostosis. Further genetic studies
      are warranted into the genetic basis of the retinol-AS relationship.

PMID- 18050374
TI  - Prevalence of ossification of posterior longitudinal ligament in patients with
      ankylosing spondylitis.
AB  - OBJECTIVE: To determine the prevalence of ossification of the posterior
      longitudinal ligament (OPLL) in patients with ankylosing spondylitis (AS).
      METHODS: A cross-sectional radiological examination was performed in patients
      diagnosed with AS. A bone and joint radiologist screened and confirmed the
      cervical radiographs of these patients. A review of the medical records was also
      conducted to investigate the relationship between the clinical manifestations and
      the actual expression of OPLL in patients with AS. RESULTS: Among 544 patients
      with AS, 470 (86.4%) were men and 96.1% were HLA-B27-positive. The mean age was
      34.3 +/- 9.3 years and mean disease duration was 12.4 +/- 7.2 years. After
      reviewing the cervical radiographs, OPLL was found in 19 patients (3.5%; 95% CI
      1.9, 5.0). The mean age of these 19 patients was 39.9 +/- 10.7 years, and the
      male to female ratio was 18:1. Interestingly, a statistically significant number
      of patients who expressed OPLL were older (p = 0.007). However, we were unable to
      determine whether OPLL was significantly associated with AS disease duration,
      peripheral arthritis, anterior uveitis/iritis, HLA-B27, anterior atlantoaxial
      subluxation, diffuse idiopathic skeletal hyperostosis, or other paraspinal
      ligament disorders. CONCLUSION: Our study showed that the frequency of OPLL in
      Korean patients with AS was 3.5%, which was considerably lower than previously
      reported values (15.5% in 103 Mexican AS). We were able to determine that OPLL in
      AS was associated with older age.

PMID- 18050375
TI  - Relationship between spinal mobility and radiographic damage in ankylosing
      spondylitis and psoriatic spondylitis: a comparative analysis.
AB  - OBJECTIVE: To correlate measures of spinal mobility used in the assessment of
      spondyloarthritis with radiographic severity, and to compare ankylosing
      spondylitis (AS) and psoriatic spondylitis (Ps-Sp) in this clinical-radiographic
      correlation. METHODS: As part of the International SPondyloarthritis
      Interobserver Reliability Exercise (INSPIRE) study, 20 spondyloarthropathy (SpA)
      experts met for an examination exercise assessing 19 patients with SpA -- 10 with
      Ps-Sp (9 men, mean age 52 yrs, mean disease duration 17 yrs) and 9 with AS (7
      men, mean age 38 yrs, mean disease duration 16 yrs). Spearman correlation with
      bias correction was used to correlate median values of the spinal measurements
      obtained in the INSPIRE study with modified Stoke AS spinal score (mSASSS) and
      Bath AS Radiology Index-spine (BASRI-s) scores calculated by consensus of 2
      assessors. RESULTS: The 2 radiographic measures performed comparably in relation
      to clinimetrics in the SpA group as a whole. There was very good correlation
      between mSASSS and the occiput-to-wall distance, tragus-to-wall distance,
      modified Schober, and lateral spinal flexion in the entire group (rs > 0.64, p <
      0.05 for each measure). There was also good correlation between mSASSS and
      cervical rotation and chest expansion (rs = 0.58 and 0.54, p <0.05,
      respectively). The clinical-radiographic correlations were comparable in the AS
      and Ps-Sp, except for cervical rotation, which correlated better with mSASSS in
      Ps-Sp than in AS. CONCLUSION: Our study documents the structure-function
      correlations in axial SpA and provides evidence supporting application of
      radiographic and clinical measures used in AS to studies of Ps-Sp.

PMID- 18050376
TI  - Evaluation of immunogenicity of the T cell costimulation modulator abatacept in
      patients treated for rheumatoid arthritis.
AB  - OBJECTIVE: The immunogenicity of abatacept, a selective costimulation modulator,
      administered intravenously, was assessed across Phase II and III trials in
      patients with rheumatoid arthritis (RA). METHODS: Two direct-format enzyme-linked
      immunosorbent assays evaluated antibody responses [whole abatacept molecule (CTLA
      4 and Ig portion) and CTLA-4 portion only (Assay A)] in the Phase II trials.
      During the Phase III trials and 2-year open-label periods, a similar, but more
      sensitive, Assay B was employed. Serum samples collected prestudy, during
      treatment, and 56 and/or 85 days following the last dose were evaluated.
      Seropositive samples with anti-CTLA-4 reactivity and sufficiently low drug levels
      were further characterized for neutralizing activity (cell-based bioassay).
      RESULTS: A total of 2237 patients with both pre- and post-baseline serum samples
      were eligible for assessment. Of these, 62 (2.8%) patients demonstrated an anti
      abatacept or anti-CTLA-4 response, determined using either Assay A or B. Using
      the more sensitive Assay B, 60 of 1990 patients (3.0%) demonstrated an antibody
      response to the whole abatacept molecule (n = 41, 2.1%) or the CTLA-4 portion (n
      = 19, 1.0%). Of the 1764 RA patients evaluated in the Phase III studies, 203
      discontinued therapy and had sera collected 56 and/or 85 days after
      discontinuation. Patients who discontinued had a higher incidence of
      immunogenicity versus patients who did not discontinue (7.4% vs 2.6%,
      respectively). Of 20 patients positive for anti-CTLA-4 reactivity, 13 were
      eligible for assessment with the neutralization bioassay. Of these, 8 patients
      exhibited neutralizing activity. Seroconversion occurred with no adverse safety
      outcomes or effect on pharmacokinetic parameters. No consistent pattern was
      observed between antibody response and loss of efficacy (American College of
      Rheumatology 20 and Health Assessment Questionnaire responses). CONCLUSION:
      Abatacept was associated with a low incidence of immunogenicity in patients with
      RA and lacked any adverse sequelae.

PMID- 18050377
TI  - Association of periodontal disease and tooth loss with rheumatoid arthritis in
      the US population.
AB  - OBJECTIVE: To test for an association of periodontitis and tooth loss with
      rheumatoid arthritis (RA). METHODS: The third National Health and Nutrition
      Examination Survey (NHANES III) is a nationally representative cross-sectional
      survey of noninstitutionalized civilians. We included participants aged > or = 60
      years who had undergone both musculoskeletal and dental examinations. RA was
      defined based on American College of Rheumatology criteria. Dental examinations
      quantified decayed and filled surfaces, missing teeth, and periodontitis.
      Periodontitis was defined as at least 1 site exhibiting both attachment loss and
      a probing depth of > or = 4 mm. We classified dental health status as (1) no
      periodontitis, (2) periodontitis, or (3) edentulous (i.e., complete tooth loss).
      We performed multivariate multinomial logistic regression models with dental
      health status as the dependent and RA as the independent variables. RESULTS: The
      sample consisted of 4461 participants, of whom 103 were classified as having RA.
      Participants with RA had more missing teeth (20 vs 16 teeth; p < 0.001), but less
      decay (2% vs 4%; p < 0.001) than participants without RA. After adjusting for
      age, sex, race/ethnicity, and smoking, subjects with RA were more likely to be
      edentulous [odds ratio (OR) 2.27, 95% confidence interval (CI) 1.56 3.31] and
      have periodontitis (OR 1.82, 95% CI 1.04 3.20) compared with non-RA subjects. In
      participants with seropositive RA there was a stronger association with dental
      health status, in particular with edentulism (OR 4.5, 95% CI 1.2 17). CONCLUSION:
      RA may be associated with tooth loss and periodontitis.

PMID- 18050378
TI  - Relative efficiencies of physician/assessor global estimates and patient
      questionnaire measures are similar to or greater than joint counts to distinguish
      adalimumab from control treatments in rheumatoid arthritis clinical trials.
AB  - OBJECTIVE: To estimate relative efficiencies of the 7 rheumatoid arthritis (RA)
      Core Data Set measures to distinguish adalimumab from control treatments in 4
      clinical trials. METHODS: Four adalimumab clinical trials were analyzed for
      arithmetic and percentage changes for each Core Data Set measure from baseline to
      endpoint: 3 assessor/physician measures -- swollen joints, tender joints, and
      global estimate; 1 laboratory test -- C-reactive protein; and 3 patient measures 
      - physical function, pain, and global estimate. Relative efficiencies of each
      measure to distinguish adalimumab from control group responses were assessed,
      with tender joint count as the referent measure. RESULTS: Relative efficiencies
      were in a similar range for physician/assessor, patient, and laboratory measures,
      with some variation between trials. Among physician/assessor measures, relative
      efficiencies for global estimates were greater than for swollen and tender joint
      counts in 8/8 comparisons. Among patient measures, relative efficiencies for
      global estimates were greater than for physical function and pain scores in at
      least 6/8 comparisons. Among all measures, relative efficiencies for patient
      global estimates were greater than for swollen joint counts in 5/8 comparisons,
      and for tender joint counts in 8/8 comparisons. CONCLUSION: Patient and
      physician/assessor measures distinguished adalimumab from control treatment
      groups in similar ranges. Among all measures, physician/assessor global estimate
      was most efficient, and tender joint count least efficient, in all 4 trials. This
      information suggests that while joint counts are the most specific measure to
      assess RA, their sensitivity to detect treatment effects in patients with RA is
      generally no greater, and usually less, than other measures.

PMID- 18050379
TI  - The Italian registry of aggressive rheumatoid arthritis -- the GIARA project.
AB  - OBJECTIVE: In 1999, the Italian Society of Rheumatology started a project to
      determine the prevalence and clinical characteristics of aggressive rheumatoid
      arthritis (ARA). METHODS: For 1 year, all patients with RA for > 5 years and
      referred to participating centers were entered in a registry and classified as
      having ARA if they fulfilled the following criteria: 10 swollen joints for at
      least 6 weeks, positive rheumatoid factor (RF), and at least one bone erosion (if
      disease duration of 2 years); (a) RF-positive and having 10 swollen joints or at
      least one newly eroded joint, or (b) if RF-negative, having 10 swollen joints and
      at least one newly eroded joint (if disease duration > 2 to < 5 years). RESULTS:
      The 94 participating centers enrolled 1218 patients with RA, 1130 of whom had
      enough data to be classified as ARA (29.0%) or non-ARA (71.0%). The frequency of
      ARA was 15% in the 2-year group and 63% in the > 2 to < 5-year group, but 35% of
      the patients in the 2-year group had erosions. Bone erosions were associated with
      disease duration, a Health Assessment Questionnaire value > 1.5, female sex, and
      RF positivity. Conditions other than RA were recorded in about 50% of the
      patients, and only 30% 40% were taking disease modifying antirheumatic drugs.
      CONCLUSION: In an Italian RA population, the GIARA (Gruppo Italiano Artrite
      Reumatoide Aggressiva) criteria for ARA were met by 15% of the patients with
      disease duration of 2 years, but erosions were seen in 35%. Upon referral, most
      of the RA patients were inadequately treated and had other conditions.

PMID- 18050381
TI  - Incidence of clinically important 10-year health status and disease activity
      levels in population-based cohorts with rheumatoid arthritis.
AB  - OBJECTIVE: To calculate the average age- and sex-specific annual incidence of
      rheumatoid arthritis (RA) linked to clinically important levels of health status
      after 10 years, and to study time trends in 10-year disease status during a 6
      year period. METHODS: Patients between 20 and 79 years of age with onset of RA
      from 1988 to 1993 (n = 550) were asked to participate in a 10-year followup
      examination. Two hundred sixteen patients in different age and sex groups from 6
      different annual cohorts met during the period 1998-2003. Study variables
      included demographic variables, medication, swollen, tender and deformed joint
      counts, erythrocyte sedimentation rate, Disease Activity Score (DAS28), Health
      Assessment Questionnaire, and pain and fatigue on a 100 mm visual analog scale
      and Arthritis Impact Measurement Scale 2. Age- and sex-specific incidences of RA
      exceeding clinically important levels 10 years after disease onset were
      calculated using the Poisson distribution with 95% confidence intervals. Analysis
      of covariance and logistic regression were used to test the influence of time on
      10-year DAS28 and presence of deformed joints. RESULTS: The average annual
      incidence of cases exceeding clinically important levels in disease activity and
      health status 10 years after disease onset increased with higher age and was
      highest among women. There was a tendency to lower disease activity 10 years
      after disease onset in the latest cohorts compared to the earliest cohorts.
      CONCLUSION: These results from population-based RA incidence cohorts provide
      important information to healthcare planners and support findings of secular
      decline in disease burden.

PMID- 18050382
TI  - Clinical evidence for utilization of the A3 adenosine receptor as a target to
      treat rheumatoid arthritis: data from a phase II clinical trial.
AB  - OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3
      adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor,
      overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in
      patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally
      bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to
      dose, designed to assess the clinical activity and safety of CF101 in active RA.
      Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid
      for 12 weeks. The primary efficacy endpoint was American College of Rheumatology
      20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC
      from 18 patients. RESULTS: . Maximal responses were observed with 1.0 mg bid,
      lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients
      receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively.
      CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and
      rash (2.7%) being the most common treatment-related adverse events. Statistically
      significant correlations between A3AR overexpression at baseline and ACR50 and
      ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks
      resulted in improvement in signs and symptoms of RA that did not achieve
      statistical significance, and was safe and well tolerated. The expression level
      of A3AR was directly correlated with patient responses to CF101, suggesting its
      utilization as a biomarker for the pharmacodynamic and therapeutic effects of
      this novel agent. These findings require confirmation in a double-blind
      randomized placebo-controlled trial, currently under way.

PMID- 18050383
TI  - Subclinical coronary artery calcification and relationship to disease duration in
      women with rheumatoid arthritis.
AB  - OBJECTIVE: To examine the association between disease duration of rheumatoid
      arthritis (RA) and the presence and extent of coronary artery calcification (CAC)
      in women with RA. METHODS: In this cross-sectional study, 185 women with RA
      duration of at least 2 years and no clinical cardiovascular disease completed
      electron-beam tomography (EBT) scans and risk factor assessment. Multivariable
      logistic regression was used to associate RA duration quartiles with subclinical
      CAC and extent of CAC. RESULTS: Age was similar across the quartiles of RA
      duration. Patients with RA > 23 years had significant increased odds (unadjusted
      OR 2.60, 95% CI 1.21 5.53) of having more extensive CAC compared to the referent
      group, those with RA for 2 7 years. This association remained significant after
      adjustment for traditional coronary heart disease (CHD) risk factors and RA
      related covariates. Patients with intermediate RA duration (8 13 yrs) were more
      likely to have presence of any CAC (OR 3.03, 95% CI 1.06 8.66) compared to the
      referent group only after adjusting for age, race, and traditional CHD risk
      factors. Patients with longer RA duration were more likely to have cumulative
      joint damage, manifested as prior joint surgery, joint deformity, and greater
      functional disability. Lower body mass index also was associated with longer RA
      duration. CONCLUSION: Patients with longstanding RA have more extensive
      subclinical atherosclerosis or CAC compared to patients of the same age,
      independent of other CHD risk factors. RA duration may be a surrogate for factors
      related to the disease process or its treatment that may promote coronary
      atherogenesis.

PMID- 18050384
TI  - Clinical and ultrasonographic monitoring of response to adalimumab treatment in
      rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate by clinical, laboratory, and sonographic assessment the
      effects of adalimumab therapy in patients with rheumatoid arthritis (RA) over 24
      months of treatment. METHODS: Twenty-five patients with RA were commenced on
      adalimumab therapy. Before the beginning of the therapy (Time 0) and after 3
      (T1), 12 (T2), and 24 (T3) months we evaluated erythrocyte sedimentation rate, C
      reactive protein, physician and patient visual analog scale for disease activity,
      number of tender and swollen joints, Health Assessment Questionnaire, and Disease
      Activity Score in 28 joints. In addition, musculoskeletal ultrasound (US) was
      performed bilaterally in the 2nd and 5th metacarpophalangeal, 3rd
      interphalangeal, wrist, and knee joints and in the tendon sheaths and bursae of
      those areas. A semiquantitative score (0 3) was used to indicate the presence of
      a localized inflammatory process and/or structural damage. The summed total was
      used as an indicator of global change in each joint (single joint score). The sum
      of the single joint scores was used as an indicator of overall polyarticular
      involvement in each patient (total score). RESULTS: Patients who did not submit
      to the planned examinations strictly on time were excluded from the study. Then
      25 patients were examined at T0 and T1, 20 at T2, and 9 at T3. All clinical and
      laboratory measures as well as the US scores were significantly reduced during
      the followup. CONCLUSION: A positive response to treatment with adalimumab was
      demonstrated by clinical, laboratory, and US evaluation by both short- and
      longterm followup.

PMID- 18050385
TI  - Improved health-related quality of life for patients with active rheumatoid
      arthritis receiving rituximab: Results of the Dose-Ranging Assessment:
      International Clinical Evaluation of Rituximab in Rheumatoid Arthritis (DANCER)
      Trial.
AB  - OBJECTIVE: To evaluate the effect of rituximab treatment on health-related
      quality of life (HRQOL) in patients with active rheumatoid arthritis (RA), who
      have had an inadequate response to disease-modifying antirheumatic drugs,
      including biologic agents. METHODS: A randomized, multicenter, double-blind,
      placebo-controlled clinical trial involving 367 rheumatoid factor-positive
      patients was conducted. Patients received 2 infusions 2 weeks apart of placebo (n
      = 122), rituximab 500 mg (n = 123), or rituximab 1000 mg (n = 122), with or
      without glucocorticoids. All patients received stable doses of methotrexate (10
      25 mg/wk). Measures included SF-36, assessed at baseline and at 24 weeks, as well
      as the HAQ and FACIT-Fatigue scale assessed at baseline and monthly for 24 weeks.
      Patients exceeding prespecified minimal clinically important differences (MCID)
      were examined. Clinical efficacy measurements (ACR20/50/70 and EULAR responses)
      were compared with HRQOL outcomes. RESULTS: At 24 weeks, the rituximab 500 mg and
      1000 mg groups both reported statistically significantly greater improvements on
      the SF-36 physical component summary (4.37 and 4.89 points higher, respectively,
      vs placebo; p < 0.001). SF-36 physical function, bodily pain, vitality, social
      function, and role-physical subscale scores also statistically significantly
      improved vs placebo. At 24 weeks, 62.6% and 67.2% of the rituximab 500 mg and
      1000 mg groups, respectively, exceeded the MCID of 0.22 in HAQ (p < 0.001). For
      FACIT-Fatigue, 55.3% and 65.6% of patients exceeded the MCID of 3.5 points
      compared with 35.2% of placebo over 24 weeks (p < 0.001). ACR20/50/70 and EULAR
      responders demonstrated greater improvements in mean baseline to 24 week changes
      in SF-36 and FACIT-Fatigue scores compared with nonresponders (p < 0.05).
      CONCLUSION: Both rituximab doses in combination with methotrexate were effective
      in improving all HRQOL outcomes in patients with active RA consistent with
      clinical efficacy.

PMID- 18050386
TI  - Increased augmentation index in rheumatoid arthritis and its relationship to
      coronary artery atherosclerosis.
AB  - OBJECTIVE: Arterial stiffness, assessed by the augmentation index and pulse wave
      velocity, is an independent risk factor for cardiovascular disease. Rheumatoid
      arthritis (RA) is associated with accelerated atherosclerosis and increased
      cardiovascular mortality. We examined the hypothesis that augmentation index and
      pulse wave velocity are increased in RA, and are related to coronary artery
      atherosclerosis. METHODS: We measured augmentation index and brachial pulse wave
      velocity in 117 patients with RA [57 with early (< 6 yrs) and 60 with late
      disease (> 10 yrs)] and 65 healthy controls. Coronary artery calcification was
      measured by electron beam computed tomography. Augmentation index and pulse wave
      velocity were compared in patients with early RA, late RA, and controls, and the
      association with coronary atherosclerosis was examined. RESULTS: Patients with
      late RA had a higher augmentation index (median 33.8%, interquartile range 27.5%
      37.0%) than those with early disease (median 27.5%, IQR 21.0% 34.0%) (p = 0.008)
      and controls (median 27.0%, IQR 20.4% 33.0%) (p < 0.001). After adjusting for
      height and cardiovascular risk factors, the association between late disease and
      augmentation index remained significant (p = 0.02). Augmentation index was
      associated with coronary calcification score (rs = 0.19, p = 0.046), and the
      association was marginal after adjustment for cardiovascular risk factors,
      disease status, and disease activity (p = 0.09). There was no significant
      difference in brachial pulse wave velocity among patients with late (9.2 +/- 1.7
      m/s) and early RA (9.1 +/- 1.6 m/s) and controls (8.9 +/- 1.5 m/s) (p = 0.78).
      CONCLUSION: Patients with RA have increased augmentation index independent of
      cardiovascular risk factors. Augmentation index was associated with coronary
      artery calcification in patients with RA; this was attenuated after adjusting for
      cardiovascular risk factors.

PMID- 18050387
TI  - Requirement of methotrexate in combination with anti-tumor necrosis factor-alpha
      therapy for adequate suppression of osteoclastogenesis in rheumatoid arthritis.
AB  - OBJECTIVE: To determine that concomitant use of methotrexate (MTX) is required to
      achieve adequate suppression of bone destruction in treating rheumatoid arthritis
      (RA) with tumor necrosis factor-alpha (TNF-alpha)-inhibiting biologic therapy. We
      quantitatively compared the suppressive effects of treatment with a combination
      of infliximab and MTX and treatment with each of these 2 agents alone on bone
      destruction in SCID-HuRAg-pit mice. METHODS: Tissue derived from human RA pannus
      was implanted with a slice of dentin subcutaneously in the backs of SCID mice
      (SCID-HuRAg-pit model). Infliximab was administered daily to SCID-HuRAg-pit mice
      using an osmotic pump for 2 weeks with or without oral administration of MTX.
      Histological changes in tissue and the pits formed on the dentin slice were
      examined 8 weeks after transplant. Serum concentrations of TNF-alpha and
      interleukin 6 (IL-6) were also measured. RESULTS: Treatment with a combination of
      infliximab and MTX suppressed pit formation significantly, while treatment with
      neither infliximab alone nor MTX alone had a significant effect on pit formation.
      Synovial inflammation and serum TNF-alpha and IL-6 levels were suppressed by
      infliximab with or without MTX. CONCLUSION: This is the first evidence in an
      animal model of arthritis that concomitant use of MTX is required to achieve
      adequate suppression of bone destruction when treating RA with a TNF-alpha
      inhibiting biologic. Our findings suggest that infliximab suppresses bone
      destruction through a mechanism of action different from that mediating its
      antiinflammatory effects in the treatment of RA.

PMID- 18050388
TI  - Web resources for C. elegans studies.

PMID- 18050389
TI  - Pristionchus pacificus genetic protocols.

PMID- 18050390
TI  - Interactions with microbial pathogens.
AB  - A wide variety of bacterial pathogens, as well as several fungi, kill C. elegans
      or produce non-lethal disease symptoms. This allows the nematode to be used as a
      simple, tractable model host for infectious disease. Human pathogens that affect
      C. elegans include gram-negative bacteria of genera Burkholderia, Pseudomonas,
      Salmonella, Serratia and Yersinia; gram-positive bacteria Enterococcus,
      Staphylococcus and Streptococcus; and the fungus Cryptococcus neoformans.
      Microbes that are not pathogenic to mammals, such as the insect pathogen Bacillus
      thuringiensis and the nematode-specific Microbacterium nematophilum, are also
      studied with C. elegans. Many of the pathogens investigated colonize the C.
      elegans intestine, and pathology is usually quantified as decreased lifespan of
      the nematode. A few microbes adhere to the nematode cuticle, while others produce
      toxins that kill C. elegans without a requirement for whole, live pathogen cells
      to contact the worm. The rapid growth and short generation time of C. elegans
      permit extensive screens for mutant pathogens with diminished killing, and some
      of the factors identified in these screens have been shown to play roles in
      mammalian infections. Genetic screens for toxin-resistant C. elegans mutants have
      identified host pathways exploited by bacterial toxins.

PMID- 18050391
TI  - Natural variation and population genetics of Caenorhabditis elegans.
AB  - C. elegans presents a low level of molecular diversity, which may be explained by
      its selfing mode of reproduction. Recent work on the genetic structure of natural
      populations of C. elegans indeed suggests a low level of outcrossing, and little
      geographic differentiation because of migration. The level and pattern of
      molecular diversity among wild isolates of C. elegans are compared with those
      found after accumulation of spontaneous mutations in the laboratory. The last
      part of the chapter reviews phenotypic differences among wild isolates of C.
      elegans.

PMID- 18050392
TI  - Evolution of development in nematodes related to C. elegans.
AB  - The knowledge about C. elegans provides a paradigm for comparative studies.
      Nematodes are very attractive in evolutionary developmental biology given the
      species richness of the phylum and the easiness with which several of these
      species can be cultured under laboratory conditions. Embryonic, gonad, vulva and
      male tail development were studied and compared in nematodes of five different
      families, providing a detailed picture of evolutionary changes in development. In
      particular, vulva development has been studied in great detail and substantial
      differences in the cellular, genetic and molecular mechanisms have been observed
      between C. elegans and other nematodes. For example, vulva induction relies on
      the single anchor cell in C. elegans, whereas a variety of different cellular
      mechanisms are used in related species. In recent years, a few species have been
      developed as satellite systems for detailed genetic and molecular studies, such
      as Oscheius tipulae and Pristionchus pacificus.

PMID- 18050393
TI  - Nematode genome evolution.
AB  - Nematodes are the most abundant type of animal on earth, and live in hot springs,
      polar ice, soil, fresh and salt water, and as parasites of plants, vertebrates,
      insects, and other nematodes. This extraordinary ability to adapt, which hints at
      an underlying genetic plasticity, has long fascinated biologists. The fully
      sequenced genomes of Caenorhabditis elegans and Caenorhabditis briggsae, and
      ongoing sequencing projects for eight other nematodes, provide an exciting
      opportunity to investigate the genomic changes that have enabled nematodes to
      invade many different habitats. Analyses of the C. elegans and C. briggsae
      genomes suggest that these include major changes in gene content; as well as in
      chromosome number, structure and size. Here I discuss how the data set of ten
      genomes will be ideal for tackling questions about nematode evolution, as well as
      questions relevant to all eukaryotes.

PMID- 18050394
TI  - The phylogenetic relationships of Caenorhabditis and other rhabditids.
AB  - C. elegans is a member of a group of nematodes called rhabditids, which
      encompasses a large number of ecologically and genetically diverse species. A
      new, preliminary phylogenetic analysis is presented for concatenated sequences of
      three nuclear genes for 48 rhabditid and diplogastrid species (including 10
      Caenorhabditis species), as well as four species representing the outgroup.
      Although many relationships are well-resolved, more data are still needed to
      resolve some key relationships, particularly near the base of the rhabditid tree.
      There is high confidence for two major clades: (1) a clade comprising
      Mesorhabditis Parasitorhabditis, Pelodera, Teratorhabditis plus a few other
      species; (2) a large clade (Eurhabditis) comprising most of the remaining
      rhabditid genera, including Caenorhabditis and its sistergroup Protorhabditis
      Prodontorhabditis-Diploscapter. Eurhabditis also contains the parasitic
      strongylids, the entomopathogenic Heterorhabditis, and the monophyletic group
      Oscheius which includes the satellite model organism O. tipulae. The
      relationships within Caenorhabditis are well resolved. The analysis also suggests
      that rhabditids include diplogastrids, to which the second satellite model
      organism Pristionchus pacificus belongs. Genetic disparity within Caenorhabditis
      is as great as that across vertebrates, suggesting Caenorhabditis lineages are
      quickly evolving, ancient, or both. The phylogenetic tree can be used to
      reconstruct evolutionary events within rhabditids. For instance, the reproductive
      mode changed multiple times from gonochorism to hermaphroditism, but only once
      from hermaphroditism to gonochorism. Complete retraction of the male tail tip,
      leading to a blunt, peloderan tail, evolved at least once. Reversions to
      unretracted tail tips occurred within both major rhabditid groups. The phylogeny
      also provides a guide to species which would be good candidates for future genome
      projects and comparative studies.

PMID- 18050395
TI  - Introduction to nematode evolution and ecology.

PMID- 18050396
TI  - Egg-laying.
AB  - C. elegans hermaphrodites are self-fertile, and their rate and temporal pattern
      of egg-laying are modulated by diverse environmental cues. Egg-laying behavior
      has served as an important phenotypic assay for the genetic dissection of
      neuronal signal transduction mechanisms. This chapter reviews our current
      understanding of the neuronal and neurochemical mechanisms underlying the control
      of egg-laying in C. elegans. The roles of specific neurons in the egg-laying
      motor circuit, which release multiple neurotransmitters affecting distinct
      parameters of egg-laying muscle activity, and the possible mechanisms for sensory
      control of egg-laying behavior, are discussed.

PMID- 18050397
TI  - GABA.
AB  - The most abundant synapses in the central nervous system of vertebrates are
      inhibitory synapses that use the neurotransmitter gamma-aminobutyric acid (GABA).
      GABA is also an important neurotransmitter in C. elegans; however, in contrast to
      vertebrates where GABA acts at synapses of the central nervous system, in
      nematodes GABA acts primarily at neuromuscular synapses. Specifically, GABA acts
      to relax the body muscles during locomotion and foraging and to contract the
      enteric muscles during defecation. The importance of this neurotransmitter for
      basic motor functions of the worm has facilitated the genetic analysis of
      proteins required for GABA function. Genetic screens have identified the GABA
      biosynthetic enzyme, the vesicular transporter, inhibitory and excitatory
      receptors, and a transcription factor required for the differentiation of GABA
      cell identity. The plasma membrane transporter and other GABA receptors have been
      identified by molecular criteria.

PMID- 18050398
TI  - Synaptic function.
AB  - C. elegans has emerged as a powerful genetic model organism in which to study
      synaptic function. Most synaptic proteins in the C. elegans genome are highly
      conserved and mutants can be readily generated by forward and reverse genetics.
      Most C. elegans synaptic protein mutants are viable affording an opportunity to
      study the functional consequences in vivo. Recent advances in
      electrophysiological approaches permit functional analysis of mutant synapses in
      situ. This has contributed to an already powerful arsenal of techniques available
      to study synaptic function in C. elegans. This review highlights C. elegans
      mutants affecting specific stages of the synaptic vesicle cycle, with emphasis on
      studies conducted at the neuromuscular junction.

PMID- 18050399
TI  - Potassium channels in C. elegans.
AB  - Ion channels are the "transistors" (electronic switches) of the brain that
      generate and propagate electrical signals in the aqueous environment of the brain
      and nervous system. Potassium channels are particularly important because, not
      only do they shape dynamic electrical signaling, they also set the resting
      potentials of almost all animal cells. Without them, animal life as we know it
      would not exist, much less higher brain function. Until the completion of the C.
      elegans genome sequencing project the size and diversity of the potassium channel
      extended gene family was not fully appreciated. Sequence data eventually revealed
      a total of approximately 70 genes encoding potassium channels out of the more
      than 19,000 genes in the genome. This seemed to be an unexpectedly high number of
      genes encoding potassium channels for an animal with a small nervous system of
      only 302 neurons. However, it became clear that potassium channels are expressed
      in all cell types, not only neurons, and that many cells express a complex
      palette of multiple potassium channels. All types of potassium channels found in
      C. elegans are conserved in mammals. Clearly, C. elegans is "simple" only in
      having a limited number of cells dedicated to each organ system; it is certainly
      not simple with respect to its biochemistry and cell physiology.

PMID- 18050400
TI  - Synaptogenesis.
AB  - Synaptogenesis is a process involving the formation of a neurotransmitter release
      site in the presynaptic neuron and a receptive field at the postsynaptic
      partners, and the precise alignment of pre- and post-synaptic specializations. In
      C. elegans synapses are found as en passant axonal swellings along the nerve
      processes. Genetic screens using a synaptic vesicle-associated GFP marker have
      identified key players in synaptic target recognition and organization of the
      presynaptic terminals. Importantly, the functions of most genes are
      evolutionarily conserved. Further studies using a combination of genetic modifier
      screens and reverse genetics have begun to reveal the underlying signaling
      pathways.

PMID- 18050401
TI  - Specification of the nervous system.
AB  - Nervous systems are characterized by an astounding degree of cellular diversity.
      The nematode Caenorhabditis elegans has served as a valuable model system to
      define the genetic programs that serve to generate cellular diversity in the
      nervous system. This review discusses neuronal diversity in C. elegans and
      provides an overview of the molecular mechanisms that define and specify neuronal
      cell types in C. elegans.

PMID- 18050402
TI  - Wnt signaling.
AB  - The use of Wnt ligands for signaling between cells is a conserved feature of
      metazoan development. Activation of Wnt signal transduction pathways upon ligand
      binding can regulate diverse processes including cell proliferation, migration,
      polarity, differentiation and axon outgrowth. A 'canonical' Wnt signaling pathway
      has been elucidated in vertebrate and invertebrate model systems. In the
      canonical pathway, Wnt binding leads to the stabilization of the transcription
      factor beta-catenin, which enters the nucleus to regulate Wnt pathway target
      genes. However, Wnt binding also acts through beta-catenin-independent,
      noncanonical pathways, such as the planar cell polarity (PCP) pathway and a
      pathway involving Ca2+ signaling. This chapter examines our current understanding
      of Wnt signaling and Wnt-mediated processes in the nematode C. elegans. Like
      other species, the C. elegans genome encodes multiple genes for Wnt ligands
      (five) and Wnt receptors (four frizzleds, one Ryk/Derailed). Unlike vertebrates
      or Drosophila, the C. elegans genome encodes three beta-catenin genes, which
      appear to have distinct functions in Wnt signaling and cell adhesion. Canonical
      Wnt signaling clearly exists in C. elegans, utilizing the beta-catenin BAR-1.
      However, a noncanonical pathway utilizing the beta-catenin WRM-1 also exists, and
      to date a similar pathway has not been described in other species. Evidence for
      beta-catenin independent noncanonical Wnt signaling is currently limited. The
      role of Wnt signaling in over a dozen C. elegans developmental processes,
      including the regulation of cell fate, polarity and migration, is described.

PMID- 18050403
TI  - LIN-12/Notch signaling in C. elegans.
AB  - Receptors of the LIN-12/Notch family mediate cell-cell interactions during animal
      development, and aberrations in LIN-12/Notch signaling have been implicated in
      human disease. Studies in C. elegans have been instrumental in defining the basic
      features of the LIN-12/Notch pathway, the role of LIN-12/Notch proteins as
      receptors for intercellular signals, the mechanism of signal transduction, and
      the regulation of LIN-12/Notch signaling during cell fate decisions. This chapter
      is focused on detailing how the "awesome power of C. elegans genetics" has
      identified many core components and modulators of LIN-12/Notch activity.

PMID- 18050404
TI  - TGF-beta signaling.
AB  - TGF-beta superfamily ligands play fundamental roles in the development and
      physiology of diverse animal species. Genetic and genomic analyses in the model
      organism Caenorhabditis elegans have contributed to the understanding of TGF-beta
      related signal transduction mechanisms. In this chapter, I describe the currently
      characterized TGF-beta-related signals and signal transduction cassettes in C.
      elegans. Homology searches of the genome identify five TGF-beta-related genes,
      for which functions have been identified for three. Two of the TGF-beta-related
      genes, daf-7 and dbl-1, function through conventional signaling pathways. These
      signaling pathways are comprised of ser/thr kinase receptors, Smads, and
      transcription co-factors. A third TGF-beta-related gene, unc-129, functions in
      axonal guidance using novel signaling mechanisms. Thus, TGF-beta-related
      signaling in C. elegans proceeds via both conserved and novel paradigms that can
      inform studies in other animal systems.

PMID- 18050405
TI  - Genomic overview of protein kinases.
AB  - Protein kinases are one of the largest and most influential of gene families:
      constituting some 2% of the proteome, they regulate almost all biochemical
      pathways and may phosphorylate up to 30% of the proteome. Bioinformatics and
      comparative genomics were used to determine the C. elegans kinome and put it in
      evolutionary and functional context. Kinases are deeply conserved in evolution,
      and the worm has family homologs for over 80% of the human kinome. Almost half of
      the 438 worm kinases are members of worm-specific or worm-expanded families. Such
      radiations include genes involved in spermatogenesis, chemosensation, Wnt
      signaling and FGF receptor-like kinases. The C. briggsae kinome is largely
      similar apart from the expanded classes, showing that such expansions are
      evolutionarily recent.

PMID- 18050407
TI  - Notch signaling in the C. elegans embryo.
AB  - Cell-cell interactions mediated by the Notch signaling pathway occur throughout
      C. elegans embryogenesis. These interactions have major roles in specifying cell
      fates and in tissue morphogenesis. The network of Notch interactions is linked in
      part through the Notch-regulated expression of components of the pathway,
      allowing one interaction to pattern subsequent ones. The Notch signal
      transduction pathway is highly conserved in animal embryogenesis. The REF-1
      family of bHLH transcription factors are major targets of Notch signaling in the
      C. elegans embryo, and are distantly related to HES proteins that are targets of
      Notch signaling in Drosophila and vertebrates.

PMID- 18050408
TI  - Epidermal morphogenesis.
AB  - The morphogenesis of the C. elegans embryo is largely controlled by the
      development of the epidermis, also known as the hypodermis, a single epithelial
      layer that surrounds the animal. Morphogenesis of the epidermis involves cell
      cell interactions with internal tissues, such as the developing nervous system
      and musculature. Genetic analysis of mutants with aberrant epidermal morphology
      has defined multiple steps in epidermal morphogenesis. In the wild type,
      epidermal cells are generated on the dorsal side of the embryo among the progeny
      of four early embryonic blastomeres. Specification of epidermal fate is regulated
      by a hierarchy of transcription factors. After specification, dorsal epidermal
      cells rearrange, a process known as dorsal intercalation. Most epidermal cells
      fuse to generate multinucleate syncytia. The dorsally located epidermal sheet
      undergoes epiboly to enclose the rest of the embryo in a process known as ventral
      enclosure; this movement requires both an intact epidermal layer and substrate
      neuroblasts. At least three distinct types of cellular behavior underlie the
      enclosure of different regions of the epidermis. Following enclosure, the
      epidermis elongates, a process driven by coordinated cell shape changes.
      Epidermal actin microfilaments, microtubules, and intermediate filaments all play
      roles in elongation, as do body wall muscles. The final shape of the epidermis is
      maintained by the collagenous exoskeleton, secreted by the apical surface of the
      epidermis.

PMID- 18050409
TI  - Gastrulation in C. elegans.
AB  - Gastrulation is the process by which the germ layers become positioned in an
      embryo. C. elegans gastrulation serves as a model for studying the molecular
      mechanisms of diverse cellular and developmental phenomena, including
      morphogenesis, cell polarization, cell-cell signaling, actomyosin contraction and
      cell-cell adhesion. One distinct advantage of studying these phenomena in C.
      elegans is that genetic tools can be combined with high resolution live cell
      imaging and direct manipulations of the cells involved. Here we review what is
      known to date about the cellular and molecular mechanisms that function in C.
      elegans gastrulation.

PMID- 18050410
TI  - Translational control of maternal RNAs.
AB  - Early development of many species depends on the temporal and spatial control of
      maternal gene products. This review discusses the control of maternal mRNAs that
      encode regulators of C. elegans embryogenesis. In the C. elegans embryo, maternal
      mRNA regulation is crucial to the patterning of early cell fates. Translational
      control of key mRNAs spatially organizes cell signaling pathways, localizes
      transcription factor activities, and controls germ cell precursor development.
      From the few mRNAs studied thus far, some themes are beginning to emerge. Control
      of maternal mRNA translation begins in the hermaphrodite germ line. Distinct
      regulatory systems keep mRNAs silent during different stages of oogenesis, and
      lead to precise temporal and spatial patterns of translation in the embryo. In
      the embryo, cell polarity factors control the localization of translational
      regulators. Each maternal mRNA contains multiple elements in its 3' untranslated
      region (3' UTR) that specify the timing and localization of translation. A
      relatively small number of RNA-binding proteins likely control many mRNAs through
      these 3' UTR elements. Therefore, the combination of RNA elements and the
      regulatory complexes recruited to them specify unique patterns of translation for
      different mRNAs. The mechanisms of translational control are only beginning to be
      explored, but are likely to regulate diverse developmental and cellular events in
      metazoans.

PMID- 18050411
TI  - Asymmetric cell division and axis formation in the embryo.
AB  - Asymmetric cell divisions play an important role in generating diversity during
      metazoan development. In the early C. elegans embryo, a series of asymmetric
      divisions are crucial for establishing the three principal axes of the body plan
      (AP, DV, LR) and for segregating determinants that specify cell fates. In this
      review, we focus on events in the one-cell embryo that result in the
      establishment of the AP axis and the first asymmetric division. We first describe
      how the sperm-derived centrosome initiates movements of the cortical actomyosin
      network that result in the polarized distribution of PAR proteins. We then
      briefly discuss how components acting downstream of the PAR proteins mediate
      unequal segregation of cell fate determinants to the anterior blastomere AB and
      the posterior blastomere P1. We also review how a heterotrimeric G protein
      pathway generates cortically based pulling forces acting on astral microtubules,
      thus mediating centrosome and spindle positioning in response to AP polarity
      cues. In addition, we briefly highlight events involved in establishing the DV
      and LR axes. The DV axis is established at the four-cell stage, following
      specific cell-cell interactions that occur between P2 and EMS, the two daughters
      of P1, as well as between P2 and ABp, a daughter of AB. The LR axis is
      established shortly thereafter by the division pattern of ABa and ABp. We
      conclude by mentioning how findings made in early C. elegans embryos are relevant
      to understanding asymmetric cell division and pattern formation across metazoan
      evolution.

PMID- 18050412
TI  - Control of oocyte meiotic maturation and fertilization.
AB  - Sexual reproduction depends upon meiosis for the generation of haploid gamete
      nuclei, which unite after fertilization to form the diploid zygote. The oocytes
      of most animal species arrest during meiotic prophase, and complete meiosis in
      response to intercellular signaling in a process called meiotic maturation.
      Oocyte meiotic maturation is defined by the transition between diakinesis and
      metaphase of meiosis I and is accompanied by nuclear envelope breakdown,
      rearrangement of the cortical cytoskeleton, and meiotic spindle assembly. Thus,
      the meiotic maturation process is essential for meiosis and prepares the oocyte
      for fertilization. In C. elegans, the processes of meiotic maturation, ovulation,
      and fertilization are temporally coupled: sperm utilize the major sperm protein
      as a hormone to trigger oocyte meiotic maturation, and in turn, the maturing
      oocyte signals its own ovulation thereby facilitating fertilization. This chapter
      highlights recent advances in understanding meiotic maturation signaling and
      gametic interactions required for fertilization.

PMID- 18050413
TI  - Germline proliferation and its control.
AB  - The C. elegans germ line proliferates from one primordial germ cell (PGC) set
      aside in the early embryo to over a thousand cells in the adult. Most germline
      proliferation is controlled by the somatic distal tip cell, which provides a stem
      cell niche at the distal end of the adult gonad. The distal tip cell signals to
      the germ line via the Notch signaling pathway, which in turn controls a network
      of RNA regulators. The FBF-1 and FBF-2 RNA-binding proteins promote continued
      mitoses in germ cells located close to the distal tip cell, while the GLD-1, GLD
      2, GLD-3, and NOS-3 RNA regulators promote entry into meiosis as germ cells leave
      the stem cell niche. In addition to these key regulators, many other genes affect
      germline proliferation.

PMID- 18050414
TI  - Specification of the germ line.
AB  - In C. elegans, the germ line is set apart from the soma early in embryogenesis.
      Several important themes have emerged in specifying and guiding the development
      of the nascent germ line. At early stages, the germline blastomeres are
      maintained in a transcriptionally silent state by the transcriptional repressor
      PIE-1. When this silencing is lifted, it is postulated that correct patterns of
      germline gene expression are controlled, at least in part, by MES-mediated
      regulation of chromatin state. Accompanying transcriptional regulation by PIE-1
      and the MES proteins, RNA metabolism in germ cells is likely to be regulated by
      perinuclear RNA-rich cytoplasmic granules, termed P granules. This chapter
      discusses the molecular nature and possible roles of these various germline
      regulators, and describes a recently discovered mechanism to protect somatic
      cells from following a germline fate.

PMID- 18050415
TI  - Introduction to the germ line.

PMID- 18050416
TI  - X-Chromosome dosage compensation.
AB  - In mammals, flies, and worms, sex is determined by distinctive regulatory
      mechanisms that cause males (XO or XY) and females (XX) to differ in their dose
      of X chromosomes. In each species, an essential X chromosome-wide process called
      dosage compensation ensures that somatic cells of either sex express equal levels
      of X-linked gene products. The strategies used to achieve dosage compensation are
      diverse, but in all cases, specialized complexes are targeted specifically to the
      X chromosome(s) of only one sex to regulate transcript levels. In C. elegans,
      this sex-specific targeting of the dosage compensation complex (DCC) is
      controlled by the same developmental signal that establishes sex, the ratio of X
      chromosomes to sets of autosomes (X:A signal). Molecular components of this
      chromosome counting process have been defined. Following a common step of
      regulation, sex determination and dosage compensation are controlled by distinct
      genetic pathways. C. elegans dosage compensation is implemented by a protein
      complex that binds both X chromosomes of hermaphrodites to reduce transcript
      levels by one-half. The dosage compensation complex resembles the conserved 13S
      condensin complex required for both mitotic and meiotic chromosome resolution and
      condensation, implying the recruitment of ancient proteins to the new task of
      regulating gene expression. Within each C. elegans somatic cell, one of the DCC
      components also participates in the separate mitotic/meiotic condensin complex.
      Other DCC components play pivotal roles in regulating the number and distribution
      of crossovers during meiosis. The strategy by which C. elegans X chromosomes
      attract the condensin-like DCC is known. Small, well-dispersed X-recognition
      elements act as entry sites to recruit the dosage compensation complex and to
      nucleate spreading of the complex to X regions that lack recruitment sites. In
      this manner, a repressed chromatin state is spread in cis over short or long
      distances, thus establishing the global, epigenetic regulation of X chromosomes
      that is maintained throughout the lifetime of hermaphrodites.

PMID- 18050417
TI  - The evolution of nematode sex determination: C. elegans as a reference point for
      comparative biology.
AB  - Sex determination was a founding topic of C. elegans research. After three
      decades of research, a complex signal transduction pathway with multiple layers
      of regulation has been elucidated. This pathway links karyotype to phenotype by
      coordinating the development of sexually dimorphic tissues. In this article, this
      pathway is placed in two broader contexts. The first is that of nematodes and
      animals in general. The important role of C. elegans studies in revealing the
      first universally conserved component of metazoan sex determination is discussed,
      as is the role of cooption of genes into the sex determination and dosage
      compensation pathways. The second context is that of a subset of more closely
      related species, with emphasis on other members of the genus Caenorhabditis.
      Studies reviewed here have determined the gene-level conservation of the known
      pathway and the relative rates of molecular evolution in conserved components,
      and made substantial progress in the manipulation of gene activity in non-elegans
      species. Special attention is paid to the origins of hermaphroditism, which
      evolved from gonochorism through germline-specific changes in sex determination.
      Recent studies suggest that the most rapidly evolving aspects of sex
      determination are germline functions related to evolutionary shifts in mating
      systems, while somatic sex determination is relatively conservative. From all of
      these studies, a picture emerges in which C. elegans utilizes an intriguing
      mixture of general and species-specific genes and regulatory mechanisms.

PMID- 18050418
TI  - Vulval development.
AB  - C. elegans vulval development is an intensively studied example of animal
      organogenesis. A network of intercellular signaling, signal transduction, and
      transcriptional regulation underlies the precise formation of this organ, which
      is the connection between the hermaphrodite uterus and the outside of the
      nematode. A single cell of the somatic gonad, the anchor cell, organizes the
      development of the vulva from epidermal precursors as well as the physical
      connection of the epidermis with the uterus. WNT signaling acting via the HOX
      gene lin-39 renders six epidermal precursor cells competent to respond to other
      developmental signals. The anchor cell induces nearby epidermal precursor cells
      to generate vulval cells via an epidermal growth factor (EGF) signaling pathway.
      The precise pattern of vulval precursor cell fates involves the graded action of
      the EGF signaling and LIN-12 (Notch) mediated lateral signaling. EGF promotes the
      primary fate while LIN-12 promotes the secondary fate. Both EGF and LIN-12
      prevent precursor cells from adopting the tertiary fate, which generates non
      specialized epidermis. EGF-receptor and Notch signaling are antagonistic: EGF
      receptor signaling leads to down-regulation of the Notch-like receptor LIN-12,
      while LIN-12 signaling induces negative regulators of EGF-receptor signaling such
      as MAP kinase phosphatase LIP-1 and the tyrosine kinase ARK-1. The primary
      precursor cell generates vulE and vulF mature vulval cells; the pattern of vulE
      and vulF cells requires an additional signal from the anchor cell as well as WNT
      signaling. The two secondary precursor cells generate vulA, vulB1, vulB2, vulC
      and vulD cells but in mirror symmetric polar patterns: ABCD and DCBA. The
      reversed polarity of the posterior secondary precursor cell lineage requires WNT
      signaling mediated by both Frizzled class and Ryk class WNT-receptors LIN-17 and
      LIN-18, respectively. A network of transcription factors controls the seven
      mature adult cell types; these include the LIM domain protein LIN-11, the
      Pax2/5/8 protein EGL-38, the zinc finger protein LIN-29, and the Nkx6.1/6.2
      protein COG-1. The anchor cell also patterns nearby uterine cells, via the DSL
      ligand LAG-2 and LIN-12, to generate the four uv1 cells that form the tight
      connection with the vulva. This connection is initiated by the anchor cell, which
      invades between the vulF cells in a process analogous to invasive behavior of
      metastatic tumor cells. During this invasion process, the basement membranes
      between the gonad and body wall are degraded. The extensive information about
      vulval development in C. elegans has helped it become a paradigmatic case for
      identifying and studying a variety of regulatory pathways.

PMID- 18050419
TI  - Male development.
AB  - The features that differentiate the C. elegans male from the hermaphrodite arise
      during postembryonic development. The major male mating structures, consisting of
      the blunt tail with fan and rays, the hook, the spicules and proctodeum, and the
      thin body, form just before the last larval molt. Male and hermaphrodite
      embryogenesis are similar but some essential male cell fates are already
      established at hatching. The male mating structures arise from three important
      sets of male-specific blast cells. These cells generate a total of 205 male
      specific somatic cells, including 89 neurons, 36 neuronal support cells, 41
      muscles, 23 cells involved in differentiating the hindgut, and 16 hypodermal
      cells associated with mating structures. Genetic and molecular studies have
      identified many genes required for male development, most of which also function
      in the hermaphrodite. Cell-cell interactions play a role in patterning all three
      of the generative tissues. Male-specific neurons, including sensory neurons of
      the rays, hook, post-cloacal sensilla, and spicules, differentiate at the end of
      the last larval stage and send out axons to make connections into the existing
      neuropil, greatly enlarging the posterior ganglia. The hindgut is highly
      differentiated to accommodate the spicules and the joining of the reproductive
      tract to the cloaca. A complex male-specific program generates many new muscles
      for copulation. The cell lineage and genetic program that gives rise to the one
      armed male gonad appears to be a variation on that of the hermaphrodite.

PMID- 18050421
TI  - The cadherin superfamily.
AB  - The cadherins are a major class of membrane proteins with prominent roles in cell
      adhesion, and the regulation of tissue organisation and morphogenesis. The C.
      elegans genome encodes 13 cadherins, including representatives of the major
      cadherin sub-types that are conserved between insects and vertebrates: the so
      called classic, Fat-like, Flamingo and calsyntenin classes. The function of most
      of these in C. elegans is still unknown, or poorly understood, mainly because
      clear loss-of-function mutations have been isolated for only a few. As is true
      for the cadherin families of other organisms, most is known about classic
      cadherin function. C. elegans has a single classic cadherin gene, which encodes
      two isoforms: one predominantly expressed in the nervous system, and the other
      more broadly expressed in all epithelial cells. The epithelial cadherin-catenin
      complex appears to be functionally equivalent to that found in Drosophila and
      vertebrates, and is critically required for embryonic morphogenesis. Mutant
      phenotypes have also been described for cdh-3 and fmi-1, which encode a Fat-like
      cadherin, and the C. elegans Flamingo homologue, respectively. cdh-3 mutants
      display incompletely penetrant defects in the morphogenesis of hyp10, the cell
      which forms the tip of the tail, and the excretory duct cell; though the
      mechanistic role of CDH-3 in these processes is not known. FMI-1 is required
      during neuronal development consistent with the known role of the Drosophila
      homologue in controlling tissue polarity. Five of the cadherins have no obvious
      homologues beyond the nematodes, and thus may be phyla-specific.

PMID- 18050422
TI  - Cell-cycle regulation.
AB  - Cell-division control affects many aspects of development. Caenorhabditis elegans
      cell-cycle genes have been identified over the past decade, including at least
      two distinct Cyclin-Dependent Kinases (CDKs), their cyclin partners, positive and
      negative regulators, and downstream targets. The balance between CDK activation
      and inactivation determines whether cells proceed through G1 into S phase, and
      from G2 to M, through regulatory mechanisms that are conserved in more complex
      eukaryotes. The challenge is to expand our understanding of the basic cell cycle
      into a comprehensive regulatory network that incorporates environmental factors
      and coordinates cell division with growth, differentiation and tissue formation
      during development. Results from several studies indicate a critical role for CKI
      1, a CDK inhibitor of the Cip/Kip family, in the temporal control of cell
      division, potentially acting downstream of heterochronic genes and dauer
      regulatory pathways.

PMID- 18050423
TI  - Basement membranes.
AB  - Basement membranes are thin, specialized extracellular matrices surrounding most
      tissues in all metazoans. The compositions and functions of basement membranes
      have generally been well conserved throughout the subkingdom. Genetic analyses of
      basement membrane components in C. elegans have provided insights into their
      assembly and functions during development. Immuno- or GFP-tagged localization
      studies have shown that basement membranes on different tissues, or even sub
      regions of tissues, contain different sets of proteins or alternatively spliced
      isoforms of them. Several components, including laminin, perlecan, type IV
      collagen and possibly osteonectin/SPARC, are essential for completion of
      embryogenesis, being necessary for tissue organization and structural integrity.
      In contrast, type XVIII collagen and nidogen are not required for viability but
      primarily influence organization of the nervous system. All of these proteins,
      with the exception of nidogen and the addition of fibulin, have roles of varying
      degree in morphogenesis of the gonad. A major family of cellular receptors for
      basement membrane proteins, the integrins, have also been characterized in C.
      elegans. As one might expect, integrins have been shown to function in many of
      the same processes as their potential ligands, the basement membrane components.
      While much remains to be explored, studies of basement membranes in C. elegans
      have been highly informative and hold great promise for improving our
      understanding of how these structures are assembled and how they function in
      development.

PMID- 18050424
TI  - Ubiquitin-mediated pathways in C. elegans.
AB  - Ubiquitin is a highly conserved 76 amino acid polypeptide, which is covalently
      attached to target proteins to signal their degradation by the 26S proteasome or
      to modify their function or localization. Regulated protein degradation, which is
      associated with many dynamic cellular processes, occurs predominantly via the
      ubiquitin-proteasome system. Ubiquitin is conjugated to target proteins through
      the sequential actions of a ubiquitin-activating enzyme, ubiquitin-conjugating
      enzymes, and ubiquitin-protein ligases. The nematode Caenorhabditis elegans has
      one ubiquitin-activating enzyme, twenty putative ubiquitin-conjugating enzymes,
      and potentially hundreds of ubiquitin-protein ligases. Research in C. elegans has
      focused on the cellular functions of ubiquitin pathway components in the context
      of organismal development. A combination of forward genetics, reverse genetics,
      and genome-wide RNAi screens has provided information on the loss-of-function
      phenotypes for the majority of C. elegans ubiquitin pathway components.
      Additionally, detailed analysis of several classes of ubiquitin-protein ligases
      has led to the identification of their substrates and the molecular pathways that
      they regulate. This review presents a comprehensive overview of ubiquitin
      mediated pathways in C. elegans with a description of the known components and
      their identified molecular, cellular, and developmental functions.

PMID- 18050425
TI  - C. elegans microRNAs.
AB  - MicroRNAs (miRNAs) are small, non-coding regulatory RNAs found in many phyla that
      control such diverse events as development, metabolism, cell fate and cell death.
      They have also been implicated in human cancers. The C. elegans genome encodes
      hundreds of miRNAs, including the founding members of the miRNA family lin-4 and
      let-7. Despite the abundance of C. elegans miRNAs, few miRNA targets are known
      and little is known about the mechanism by which they function. However, C.
      elegans research continues to push the boundaries of discovery in this area. lin
      4 and let-7 are the best understood miRNAs. They control the timing of adult cell
      fate determination in hypodermal cells by binding to partially complementary
      sites in the mRNA of key developmental regulators to repress protein expression.
      For example, lin-4 is predicted to bind to seven sites in the lin-14 3'
      untranslated region (UTR) to repress LIN-14, while let-7 is predicted to bind two
      let-7 complementary sites in the lin-41 3' UTR to down-regulate LIN-41. Two other
      miRNAs, lsy-6 and mir-273, control left-right asymmetry in neural development,
      and also target key developmental regulators for repression. Approximately one
      third of the C. elegans miRNAs are differentially expressed during development
      indicating a major role for miRNAs in C. elegans development. Given the
      remarkable conservation of developmental mechanism across phylogeny, many of the
      principles of miRNAs discovered in C. elegans are likely to be applicable to
      higher animals.

PMID- 18050426
TI  - Trans-splicing and operons.
AB  - About 70% of C. elegans mRNAs are trans-spliced to one of two 22 nucleotide
      spliced leaders. SL1 is used to trim off the 5' ends of pre-mRNAs and replace
      them with the SL1 sequence. This processing event is very closely related to cis
      splicing, or intron removal. The SL1 sequence is donated by a 100 nt small
      nuclear ribonucleoprotein particle (snRNP). This snRNP is structurally and
      functionally related to the U snRNAs (U1, U2, U4, U5 and U6) that play key roles
      in intron removal and trans-splicing, except that it is consumed in the process
      of splicing. More than half of C. elegans pre-mRNAs are subject to SL1 trans
      splicing. About 30% are not trans-spliced at all. The remaining genes are trans
      spliced by SL2. These genes are all downstream genes in closely spaced gene
      clusters similar to bacterial operons. They are transcribed from a promoter at
      the 5' end of the cluster of between 2 and 8 genes. This transcription makes a
      polycistronic pre-mRNA that is co-transcriptionally processed by cleavage and
      polyadenylation at the 3' end of each gene, and this event is closely coupled to
      the SL2 trans-splicing event that occurs only approximately 100 nt further
      downstream. Recent studies on the mechanism of SL2 trans-splicing have revealed
      that one of the 3' end formation proteins, CstF, interacts with the only protein
      known to be specific to the SL2 snRNP. The operons contain primarily genes whose
      products are needed for mitochondrial function and the basic machinery of gene
      expression: transcription, splicing and translation. Many operons contain genes
      whose products are known to function together. This presumably provides co
      regulation of these proteins by producing a single RNA that encodes both.

PMID- 18050427
TI  - Alternative splicing in C. elegans.
AB  - Alternative splicing is a common mechanism for the generation of multiple
      isoforms of proteins. It can function to expand the proteome of an organism and
      can serve as a way to turn off gene expression post-transcriptionally. This
      review focuses on splicing and its regulation in C. elegans. The fully-sequenced
      C. elegans genome combined with its elegant genetics offers unique advantages for
      exploring alternative splicing regulation in metazoans. The topics covered in
      this review include constitutive splicing factors, identification of
      alternatively spliced genes, examples of alternative splicing in C. elegans, and
      alternative splicing regulation. Key genes whose regulated alternative splicing
      are reviewed include let-2, unc-32, unc-52, egl-15 and xol-1. Factors involved in
      alternative splicing that are discussed include mec-8, smu-1, smu-2, fox-1, exc-7
      and unc-75.

PMID- 18050428
TI  - Transcriptional regulation.
AB  - The regulation of transcription in C. elegans shares many similarities to
      transcription in other organisms. The details of how specific transcription
      factors bind to target promoters and act as either activators or repressors are
      still being examined in many cases, but an increasing number of factors and their
      binding sites are being characterized. This chapter reviews the general concepts
      that have emerged with regards to promoter function in C. elegans. Included are
      the methods that have been successfully employed as well as limitations
      encountered to date. Specific cis-acting promoter elements from myo-2, hlh-1 and
      lin-26 are discussed as examples of complex promoters regulated by multiple
      sequence elements. In addition, examples of organ-, tissue-, and cell type
      specific mechanisms for generating spatial specificity in gene expression are
      discussed.

PMID- 18050429
TI  - Caenorhabditis briggsae methods.

PMID- 18050430
TI  - Carbohydrates and glycosylation.
AB  - The C. elegans genome contains sequences similar to a large number of mammalian
      genes implicated in the assembly, processing, and modification of glycans. In
      recent years, spectacular progress has been made in developing and refining tools
      to obtain structural information with small amounts of material, increasing our
      understanding of glycan structural complexity in this organism. These approaches
      have revealed novel N- and O-glycan structures in C. elegans, as well as a high
      degree of conservation in glycosaminoglycan structure. In parallel, studies in
      which glycan structure is perturbed by genetic manipulation have begun to reveal
      the roles of specific carbohydrate moieties in developmental and physiological
      processes. This review summarizes recent work elucidating the fine structure of
      complex carbohydrates in C. elegans as well as genetic studies that have
      uncovered novel roles for complex carbohydrates in developmental processes.

PMID- 18050431
TI  - Biology and genome of Trichinella spiralis.
AB  - Clade I nematode species in the genus Trichinella can cause infections in humans
      that lead to mortality and serious morbidity. There are currently eight
      recognized species or genotypes that comprise this genus. The species display
      diverse biological characteristics, the evolutionary significance of which
      recently has been extensively clarified. Some of that diversity translates into
      variable importance as zoonotic pathogens, with T. spiralis having the highest
      significance. Trichinellosis has re-emerged as an important zoonotic infection in
      various parts of the world, reminding us that control of this infection depends
      on persistent vigilance. Trichinella species display unique and biologically
      interesting complexity in interactions with host cells that they inhabit.
      Significant progress has been made toward understanding details of these
      interactions. Progress on transcriptomics, proteomics and now genomics offers
      exciting prospects for accelerating advances in future research. An overview of
      these parasites regarding biology, significance as zoonotic pathogens and
      selected research topics is presented here.

PMID- 18050433
TI  - Chemosensation in C. elegans.
AB  - C. elegans has a highly developed chemosensory system that enables it to detect a
      wide variety of volatile (olfactory) and water-soluble (gustatory) cues
      associated with food, danger, or other animals. Much of its nervous system and
      more than 5% of its genes are devoted to the recognition of environmental
      chemicals. Chemosensory cues can elicit chemotaxis, rapid avoidance, changes in
      overall motility, and entry into and exit from the alternative dauer
      developmental stage. These behaviors are regulated primarily by the amphid
      chemosensory organs, which contain eleven pairs of chemosensory neurons. Each
      amphid sensory neuron expresses a specific set of candidate receptor genes and
      detects a characteristic set of attractants, repellents, or pheromones. About 500
      1000 different G protein-coupled receptors (GPCRs) are expressed in chemosensory
      neurons, and these may be supplemented by alternative sensory pathways as well.
      Downstream of the GPCRs, two signal transduction systems are prominent in
      chemosensation, one that uses cGMP as a second messenger to open cGMP-gated
      channels, and one that relies upon TRPV channels. These sensory pathways are
      modulated and fine-tuned by kinases and phosphatases. Chemosensory preferences
      can be modified by sensory adaptation, developmental history, and associative
      learning, allowing C. elegans to integrate context and experience into its
      behavior.

PMID- 18050434
TI  - Electrophysiological recordings from the neuromuscular junction of C. elegans.
AB  - Electrophysiology provides a quantifiable measure of synaptic activity useful in
      the functional analysis of synaptic proteins. Recent advances in the application
      of this technique to C. elegans provides a means of coupling genetics to
      electrophysiological analysis, providing new insights into the molecular
      mechanisms regulating neurotransmission. Here we describe a dissection technique
      that exposes the neuromuscular junctions of C. elegans for electrophysiological
      analysis. This technique can be adapted to record from virtually any excitable
      cell in the worm.

PMID- 18050432
TI  - Heterotrimeric G proteins in C. elegans.
AB  - Heterotrimeric G proteins, composed of alpha, beta, and gamma subunits, are able
      to transduce signals from membrane receptors to a wide variety of intracellular
      effectors. In this role, G proteins effectively function as dimers since the
      signal is communicated either by the G alpha subunit or the stable G betagamma
      complex. When inactive, G alpha-GDP associates with G betagamma and the
      cytoplasmic portion of the receptor. Ligand activation of the receptor stimulates
      an exchange of GTP for GDP resulting in the active signaling molecules G alpha
      GTP and free G betagamma, either of which can interact with effectors. Hydrolysis
      of GTP restores G alpha-GDP, which then reassociates with G betagamma and
      receptor to terminate signaling. The rate of G protein activation can be enhanced
      by the guanine-nucleotide exchange factor, RIC-8, while the rate of GTP
      hydrolysis can be enhanced by RGS proteins such as EGL-10 and EAT-16. Evidence
      for a receptor-independent G-protein-signaling pathway has been demonstrated in
      C. elegans early embryogenesis. In this pathway, the G alpha subunits GOA-1 and
      GPA-16 are apparently activated by the non-transmembrane proteins GPR-1, GPR-2,
      and RIC-8, and negatively regulated by RGS-7. The C. elegans genome encodes 21 G
      alpha, 2 G beta and 2 G gamma subunits. The alpha subunits include one ortholog
      of each mammalian G alpha family: GSA-1 (Gs), GOA-1 (Gi/o), EGL-30 (Gq) and GPA
      12 (G12). The remaining C. elegans alpha subunits (GPA-1, GPA-2, GPA-3, GPA-4,
      GPA-5, GPA-6, GPA-7, GPA-8, GPA-9, GPA-10, GPA-11, GPA-13, GPA-14, GPA-15, GPA
      16, GPA-17 and ODR-3) are most similar to the Gi/o family, but do not share
      sufficient homology to allow classification. The conserved G alpha subunits, with
      the exception of GPA-12, are expressed broadly while 14 of the new G alpha genes
      are expressed in subsets of chemosensory neurons. Consistent with their
      expression patterns, the conserved C. elegans alpha subunits, GSA-1, GOA-1 and
      EGL-30 are involved in diverse and fundamental aspects of development and
      behavior. GOA-1 acts redundantly with GPA-16 in positioning of the mitotic
      spindle in early embryos. EGL-30 and GSA-1 are required for viability starting
      from the first larval stage. In addition to their roles in development and
      behaviors such as egg laying and locomotion, the EGL-30, GSA-1 and GOA-1 pathways
      interact in a network to regulate acetylcholine release by the ventral cord motor
      neurons. EGL-30 provides the core signals for vesicle release, GOA-1 negatively
      regulates the EGL-30 pathway, and GSA-1 modulates this pathway, perhaps by
      providing positional cues. Constitutively activated GPA-12 affects pharyngeal
      pumping. The G alpha subunits unique to C. elegans are primarily involved in
      chemosensation. The G beta subunit, GPB-1, as well as the G gamma subunit, GPC-2,
      appear to function along with the alpha subunits in the classic G protein
      heterotrimer. The remaining G beta subunit, GPB-2, is thought to regulate the
      function of certain RGS proteins, while the remaining G gamma subunit, GPC-1, has
      a restricted role in chemosensation. The functional difference for most G protein
      pathways in C. elegans, therefore, resides in the alpha subunit. Many cells in C.
      elegans express multiple G alpha subunits, and multiple G protein pathways are
      known to function in specific cell types. For example, Go, Gq and Gs-mediated
      signaling occurs in the ventral cord motor neurons. Similarly, certain amphid
      neurons use multiple G protein pathways to both positively and negatively
      regulate chemosensation. C. elegans thus provides a powerful model for the study
      of interactions between and regulation of G protein signaling.

PMID- 18050435
TI  - Culture of embryonic C. elegans cells for electrophysiological and
      pharmacological analyses.
AB  - Despite the considerable advantages that C. elegans offers for studying gene
      function in vivo, this system is quite challenging for in vivo
      electrophysiological analysis of channel function, particularly in neurons. A
      major problem is that C. elegans neurons are confined in a pressurized and hard
      to-penetrate cuticle. Recently, a method for culturing C. elegans embryonic cells
      has been developed and numerous researchers have already applied this option to
      study a variety of native ion channels and transporters using various
      configurations of the patch-clamp technique. C. elegans embryonic cells are
      obtained from eggs harvested from synchronized gravid adults and then are
      dissociated using a combination of enzymatic treatment and manual pipetting. Once
      plated on a surface covered with peanut lectin, cells adhere and differentiate
      into neurons, muscle and epithelial cells. Cultured embryonic cells recapitulate
      the expression of differentiation markers and are found in the culture in
      proportion to their cell type in the mature embryo. Differentiated cells survive
      well for at least 2 weeks. It should be noted that postembryonic cells do not
      appear to be generated in these cultures. Cultures can be used for
      electrophysiological study, testing of pharmacological sensitivities, and for
      RNAi. C. elegans cell culture thus constitutes the basis for the application of
      experimental procedures that are not easily applicable to the intact nematode.

PMID- 18050436
TI  - Transcription mechanisms.
AB  - Appropriate regulation of mRNA transcription is central to the differentiation
      and functions of eukaryotic cells, and to the development of complex organisms.
      mRNAs are synthesized by the coordinated action of a set of general transcription
      and mRNA modification factors. These factors and the fundamental mechanisms
      involved in transcription are conserved among eukaryotes, including C. elegans.
      Recent studies in various systems have revealed that this apparatus is not
      controlled through a simple on/off "switch" at the promoter, and that the factors
      and mechanisms involved in transcription are instead subject to regulation at a
      surprising number of different levels. In this chapter we will discuss examples
      in which regulation involving the general mRNA transcription apparatus or other
      transcription co-factors plays a central role in C. elegans development, and in
      which C. elegans studies have provided new insights into eukaryotic transcription
      mechanisms. Together, these studies have shown that regulatory mechanisms that
      involve the general Pol II machinery are a central participant in many aspects of
      C. elegans biology.

PMID- 18050437
TI  - C. elegans network biology: a beginning.
AB  - The architecture and dynamics of molecular networks can provide an understanding
      of complex biological processes complementary to that obtained from the in-depth
      study of single genes and proteins. With a completely sequenced and well
      annotated genome, a fully characterized cell lineage, and powerful tools
      available to dissect development, Caenorhabditis elegans, among metazoans,
      provides an optimal system to bridge cellular and organismal biology with the
      global properties of macromolecular networks. This chapter considers omic
      technologies available for C. elegans to describe molecular networks-
      encompassing transcriptional and phenotypic profiling as well as physical
      interaction mapping--and discusses how their individual and integrated
      applications are paving the way for a network-level understanding of C. elegans
      biology.

PMID- 18050438
TI  - Oscheius tipulae.
AB  - Oscheius tipulae is a common soil nematode of the same family as C. elegans
      (Rhabditidae), which presents the same hermaphroditic mode of reproduction and is
      easily cultured in the same conditions. Oscheius tipulae has been used as a
      developmental genetic model system to study vulva formation. Compared to C.
      elegans, it has a simpler vulval cell lineage, a reduced competence group and a
      different mechanism of vulval cell fate patterning. The spectrum of vulval
      phenotypes obtained in genetic screens differs from that found in C. elegans. Its
      easy isolation from soil and the availability of numerous wild isolates of O.
      tipulae from all over the world facilitate population genetic and
      microevolutionary studies, especially of the evolution of cell lineage. The
      Oscheius genus also presents many species with interesting evolutionary changes
      in mode of reproduction, gonad development, body size, etc.

PMID- 18050439
TI  - Neurophysiological methods in C. elegans: an introduction.
AB  - The simple and well-defined structure of the C. elegans nervous system has made
      it an attractive model for studying the neural and genetic basis of behavior.
      However, the wider use physiological methods for monitoring neural activity in
      vivo or determining the effects of specific ion channels on neuronal function has
      been a relatively recent development. This chapter presents a compendium of
      protocols and technical reports on the current state of the art in C. elegans
      electrophysiology and neuroimaging. These include methods for calcium imaging in
      intact animals, in situ electrical recording from neurons and muscle cells, and
      in vitro recording from cultured neurons and oocytes.

PMID- 18050440
TI  - Imaging the activity of neurons and muscles.
AB  - Optical methods provide a noninvasive way to monitor the activity of neurons and
      muscles in C. elegans. Although optical techniques are of use in many
      experimental systems, they are of particular interest for C. elegans researchers.
      Worms are optically transparent, and thus can be imaged while fully intact, and a
      variety of genetically encoded indicators are available which can be targeted to
      cells of interest with appropriate promoters. Optical calcium indicators appear
      to provide a good indirect measure of the activity of neurons and muscles. This
      chapter reviews the principles of operation of some common genetically encoded
      indicators, describes the microscopy equipment and image analysis needed to
      optically measure activity, discusses general principles and pitfalls of applying
      optical methods in biological samples, and finally gives example protocols for
      imaging calcium in specific muscles and neurons.

PMID- 18050441
TI  - Heterologous expression of C. elegans ion channels in Xenopus oocytes.
AB  - Physiological methods entered the world of C. elegans, a model system used for
      many years to study development and a plethora of biological processes mainly
      employing genetic, molecular and anatomical techniques. One of the methods
      introduced by physiologists is the use of Xenopus oocytes for expression of C.
      elegans ion channels. Oocytes of the South African frog Xenopus laevis are used
      widely for the expression of mammalian channels and transporters contributing to
      numerous discoveries in these fields. They now promise to aid C. elegans
      researchers in deciphering mechanisms of channels function and regulation with
      implications for mammalian patho-physiology. Heterologous cRNA can be easily
      injected into Xenopus oocytes and translated proteins can be studied using
      several techniques including electrophysiology, immunocytochemistry and protein
      biochemistry. This chapter will focus on techniques used for oocyte preparation
      and injection, and will give a brief overview of specific methods. Limitations of
      the use of Xenopus oocytes will be also discussed.

PMID- 18050442
TI  - Electrophysiological recordings from the pharynx.

PMID- 18050443
TI  - Isolation of C. elegans and related nematodes.

PMID- 18050444
TI  - Pristionchus pacificus genomics: from genetics to genome sequence.

PMID- 18050445
TI  - Profiling C. elegans gene expression with DNA microarrays.

PMID- 18050446
TI  - Immunohistochemistry.

PMID- 18050447
TI  - Protocols for large scale in situ hybridization on C. elegans larvae.

PMID- 18050448
TI  - RNA in situ hybridization of dissected gonads.

PMID- 18050449
TI  - Reporter gene fusions.

PMID- 18050450
TI  - Genetic balancers.

PMID- 18050451
TI  - Maintenance of C. elegans.

PMID- 18050453
TI  - Nomarski images for learning the anatomy, with tips for mosaic analysis.

PMID- 18050452
TI  - Genetic dissection of developmental pathways.

PMID- 18050454
TI  - Genetic mapping and manipulation: chapter 10--Suppressor mutations.

PMID- 18050455
TI  - Genetic mapping and manipulation: chapter 9--Synthetic and enhancer mutations.

PMID- 18050456
TI  - Genetic mapping and manipulation: chapter 8--Dominant mutations.

PMID- 18050457
TI  - Genetic mapping and manipulation: chapter 7--Making compound mutants.

PMID- 18050458
TI  - Genetic mapping and manipulation: chapter 6--Mapping with deficiencies and
      duplications.

PMID- 18050459
TI  - Genetic mapping and manipulation: chapter 5--SNPs: three-point mapping.

PMID- 18050460
TI  - Genetic mapping and manipulation: chapter 4--SNPs: introduction and two-point
      mapping.

PMID- 18050461
TI  - Genetic mapping and manipulation: chapter 3--Three-point mapping with genetic
      markers.

PMID- 18050462
TI  - Genetic mapping and manipulation: chapter 2--Two-point mapping with genetic
      markers.

PMID- 18050463
TI  - Genetic mapping and manipulation: chapter 1--Introduction and basics.

PMID- 18050464
TI  - Ecology of Caenorhabditis species.
AB  - Although several Caenorhabditis species are now studied in laboratories in great
      detail, the knowledge of the ecology of most Caenorhabditis species is scarce. In
      this chapter we present data on the habitat, animal associations, and
      geographical distribution of the eighteen described and five undescribed
      Caenorhabditis species currently known to science. The habitats of these species
      are very diverse, ranging from rotting cactus tissue to inflamed auditory canals
      of zebu cattle. Some species, including C. elegans, have only been isolated from
      anthropogenic habitats. Consequently, their natural habitat is unknown. All
      Caenorhabditis species are colonizers of nutrient- and bacteria-rich substrates
      and none of them is a true soil nematode. Dauer juveniles of many Caenorhabditis
      species were shown to be associated with terrestrial arthropods or gastropods. An
      association with invertebrates is also likely for the remaining species. The type
      of association is either phoresy (for transport to a new habitat) or necromeny
      (to secure the body of the associated animal as a future food source). There are
      also some records of Caenorhabditis species associated with vertebrates. The
      Caenorhabditis stem species was probably a colonizer of nutrient-rich substrates
      and was phoretic on arthropods. Some evolutionary trends within the taxon are
      discussed.

PMID- 18050465
TI  - A quick tour of nematode diversity and the backbone of nematode phylogeny.
AB  - Contrary to textbook dogma, nematodes are not only highly diverse, but often also
      complex and biologically specialized metazoans. Just a few of the many
      fascinating adaptations are reviewed in this chapter, as a prelude to a quick
      tour through phylogenetic relationships within the phylum. Small Subunit rDNA
      sequences have confirmed several controversial prior hypotheses, as well as
      revealing some unexpected relationships, resulting in a recent proposal for
      revised classification. Three major lineages exist within the phylum:
      Chromadoria, Enoplia and Dorylaimia. The exact order of appearance of these
      lineages is not yet resolved, which also leaves room for uncertainty about the
      biology and morphology of the exclusive common ancestor of nematodes. Enoplia and
      Dorylaimia differ considerably in many respects from C. elegans, which is a
      member of Chromadoria. The latter group is extremely diverse in its own right,
      for example in ecological range, in properties of the cuticle and in structure of
      the pharynx. The formerly relatively widely accepted class Secernentea is deeply
      nested within Chromadoria, and has therefore recently been relegated to the rank
      and name of order Rhabditida. Within this order, closer relatives of C. elegans
      include strongylids, diplogasterids and bunonematids. Tylenchs, cephalobs and
      panagrolaimids are also members of Rhabditida, albeit probably more distantly
      related to C. elegans.

PMID- 18050466
TI  - Mechanosensation.
AB  - Wild C. elegans and other nematodes live in dirt and eat bacteria, relying on
      mechanoreceptor neurons (MRNs) to detect collisions with soil particles and other
      animals as well as forces generated by their own movement. MRNs may also help
      animals detect bacterial food sources. Hermaphrodites and males have 22 putative
      MRNs; males have an additional 46 MRNs, most, if not all of which are needed for
      mating. This chapter reviews key aspects of C. elegans mechanosensation,
      including MRN anatomy, what is known about their contributions to behavior as
      well as the neural circuits linking MRNs to movement. Emerging models of the
      mechanisms used to convert mechanical energy into electrical signals are also
      discussed. Prospects for future research include expanding our understanding of
      the molecular basis of mechanotransduction and how activation of MRNs guides and
      modulates behavior.

PMID- 18050467
TI  - Male mating behavior.
AB  - Caenorhabditis elegans male mating provides an excellent opportunity to determine
      how sensory perception regulates behavior and motor programs. The male-specific
      nervous system and muscles are superimposed over the general nervous system and
      musculature. Genetic screens and genomic approaches have identified male-specific
      and male-enriched genes as well as non-sex specific molecules specialized for
      mating sub-behaviors. In this chapter, we discuss the cellular, genetic, and
      molecular basis for male mating behavior.

PMID- 18050468
TI  - Ionotropic glutamate receptors: genetics, behavior and electrophysiology.
AB  - Most rapid excitatory synaptic signaling is mediated by glutamatergic
      neurotransmission. An important challenge in neurobiology is to understand the
      molecular architecture of functional glutamatergic synapses. By combining the
      techniques of genetics, molecular biology and electrophysiology in C. elegans we
      have the potential to identify and characterize the molecules that contribute to
      the function of glutamatergic synapses. In C. elegans both excitatory and
      inhibitory ionotropic glutamate receptors are linked to neural circuits and
      behavior. Genetic analysis has identified genes required for receptor expression,
      trafficking, localization, stabilization and function at synapses. Significantly,
      novel proteins required for glutamate receptor function have been discovered in
      the worm. These advances may also lead to a better understanding of glutamatergic
      signaling in vertebrates.

PMID- 18050469
TI  - Homologs of the Hh signalling network in C. elegans.
AB  - In Drosophila and vertebrates, Hedgehog (Hh) signalling is mediated by a cascade
      of genes, which play essential roles in cell proliferation and survival, and in
      patterning of the embryo, limb buds and organs. In C. elegans, this pathway has
      undergone considerable evolutionary divergence; genes encoding homologues of key
      pathway members, including Hh, Smoothened, Cos2, Fused and Suppressor of Fused,
      are absent. Surprisingly, over sixty proteins (i.e. WRT, GRD, GRL, and QUA),
      encoded by a set of genes collectively referred to as the Hh-related genes, and
      two co-orthologs (PTC-1,-3) of fly Patched, a Hh receptor, are present in C.
      elegans. Several of the Hh-related proteins are bipartite and all can potentially
      generate peptides with signalling activity, although none of these peptides
      shares obvious sequence similarity with Hh. In addition, the ptc-related (ptr)
      genes, which are present in a single copy in Drosophila and vertebrates and
      encode proteins closely related to Patched, have undergone an expansion in number
      in nematodes. A number of functions, including roles in molting, have been
      attributed to the C. elegans Hh-related, PTC and PTR proteins; most of these
      functions involve processes that are associated with the trafficking of proteins,
      sterols or sterol-modified proteins. Genes encoding other components of the Hh
      signalling pathway are also found in C. elegans, but their functions remain to be
      elucidated.

PMID- 18050470
TI  - Signaling in the immune response.
AB  - Many pathogens that can infect C. elegans have been described, including some
      that co-exist with the nematode in its natural environment. This chapter
      describes our current understanding of the different innate immune responses of
      C. elegans that follow infection. It focuses on the main signalling pathways that
      have been identified and highlights the inclusion of certain molecular cassettes
      in both immune and developmental functions.

PMID- 18050471
TI  - Nuclear hormone receptors in C. elegans.
AB  - Nuclear receptors (NRs) are transcription factors typically regulated by
      lipophilic hormones, which coordinate metazoan metabolism, development and
      homeostasis. C. elegans has undergone a remarkable expansion of the family,
      harboring 284 of these receptors in its genome. Approximately 20 of them have
      been analyzed genetically, most of which correspond to conserved homologs in
      other metazoans. These NRs variously affect broad life history traits such as sex
      determination, molting, developmental timing, diapause, and life span. They also
      impact neural development, axon outgrowth and neuronal identity. Finally, they
      influence lipid and xenobiotic metabolism. The study of C. elegans NRs holds
      great promise for dissecting nuclear receptor signaling pathways in vivo in the
      context of complex endocrine networks.

PMID- 18050473
TI  - The putative chemoreceptor families of C. elegans.
AB  - Chemoreception of environmental stimuli is a major sensory system in small soil
      nematodes like C. elegans. As in other animals, chemoreception is mediated in C.
      elegans by members of the seven-transmembrane G-protein-coupled receptor class
      (7TM GPCRs). We summarize the many large putative chemoreceptor gene families,
      including the str family (which includes odr-10, the only receptor with an
      identified ligand), and the sra, srab, srb, srbc, srd, sre, srg, srh, sri, srj,
      srm, srr, srsx, srt, sru, srv, srw, srx, srxa, and srz families. Together these
      comprise +/-1280 apparently intact genes and +/-420 apparent pseudogenes, about
      7% of the total gene count of C. elegans. These genes are unusually clustered on
      chromosomes, both within and between families, and are enigmatically concentrated
      on the large chromosome V. Comparative studies with C. briggsae have revealed
      extraordinary divergence of the chemoreceptor repertoire between the two species,
      including frequent amplifications of subfamilies in C. elegans and positive
      selection in the srz family. The size and complexity of the chemoreceptor gene
      families also facilitate studies of promoter elements using paralogous and
      orthologous comparisons, as well as other aspects of gene family and genome
      evolution.

PMID- 18050472
TI  - Small GTPases.
AB  - Small GTPases of the Ras superfamily are key regulators of diverse cellular and
      developmental events, including differentiation, cell division, vesicle
      transport, nuclear assembly, and control of the cytoskeleton. The C. elegans
      genome encodes 56 members of the major Ras GTPase subfamilies, including the
      Ras/Ral/Rap family, the Rho family, the Rab family, Ran, and the Arf/Sar family.
      Studies in C. elegans have shown that Ras/Rap family members control cell fate
      specification and differentiation; Rho GTPases control morphogenesis and actin
      dynamics, including axon pathfinding and cell migration; Rab GTPases control
      synaptic vesicle trafficking and release and gene expression responses in innate
      immunity; the Ran GTPase controls nuclear import/export, nuclear reassembly after
      mitosis, and kinetechore association with microtubules; and Arf/Sar GTPases
      control morphogenesis and microtubule organization and possibly cilia
      development. Functions for many of the small GTPases remain to be discovered, and
      continuing studies in C. elegans will elucidate the roles of these molecules in
      animal development.

PMID- 18050474
TI  - RTK/Ras/MAPK signaling.
AB  - Receptor Tyrosine Kinase (RTK)/Ras GTPase/MAP kinase (MAPK) signaling pathways
      are used repeatedly during metazoan development to control many different
      biological processes. In the nematode Caenorhabditis elegans, two different RTKs
      (LET-23/EGFR and EGL-15/FGFR) are known to stimulate LET-60/Ras and a MAPK
      cascade consisting of the kinases LIN-45/Raf, MEK-2/MEK and MPK-1/ERK. This
      Ras/MAPK cascade is required for multiple developmental events, including
      induction of vulval, uterine, spicule, P12 and excretory duct cell fates, control
      of sex myoblast migration and axon guidance, and promotion of germline meiosis.
      Studies in C. elegans have provided much insight into the basic framework of this
      RTK/Ras/MAPK signaling pathway, its regulation, how it elicits cell-type specific
      responses, and how it interacts with other signaling pathways such as the Wnt and
      Notch pathways.

PMID- 18050475
TI  - Embryological variation during nematode development.
AB  - Early cell lineages and arrangement of blastomeres in C. elegans are similar to
      the pattern found in Ascaris and other studied nematodes leading to the
      assumption that embryonic development shows little variation within the phylum
      Nematoda. However, analysis of a larger variety of species from various branches
      of the phylogenetic tree demonstrate that prominent variations in crucial steps
      of early embryogenesis exist among representatives of this taxon. So far, most of
      these variations have only been studied on a descriptive level and thus
      essentially nothing is known about their molecular or genetic basis.
      Nevertheless, it is obvious that the limited morphological diversity of the
      freshly hatched juvenile and the uniformity of the basic body plan contrast with
      the many modifications in the way a worm is generated from the egg cell. This
      chapter focuses on the initial phase between egg activation and gastrulation and
      deals with the following aspects: reproduction and diploidy, polarity, cleavage
      and germ line, cell lineages; cell cycles and maternal contribution, cell-cell
      communication and cell specification, gastrulation.

PMID- 18050476
TI  - Germline genomics.
AB  - The completion of the C. elegans genome sequence permits the comprehensive
      examination of the expression and function of genes. Annotation of virtually
      every encoded gene in the genome allows systematic analysis of those genes using
      high-throughput assays, such as microarrays and RNAi. This chapter will center on
      the use of microarrays to comprehensively identify genes with enriched expression
      in the germ line during development. This knowledge provides a database for
      further studies that focus on gene function during germline development or early
      embryogenesis. Additionally, a comprehensive overview of germline gene expression
      can uncover striking biases in how genes expressed in the germ line are
      distributed in the genome, leading to new discoveries of global regulatory
      mechanisms in the germ line.

PMID- 18050477
TI  - Germline chromatin.
AB  - The DNA in eukaryotes is wrapped around a histone octamer core, together
      comprising the main subunit of chromatin, the nucleosome. Modifications of the
      nucleosomal histones in the genome correlate with the ability or inability of
      chromatin to form higher order structures, that in turn influence gene activity.
      The genome in primordial germ cells in early C. elegans germ cells carries a
      unique pattern of histone modifications that correlate with transcriptional
      repression in these cells, and aspects of this chromatin regulation are conserved
      in Drosophila. Loss of repression causes sterility in the adults, suggesting that
      chromatin-based repression is essential for germ line maintenance. The post
      embryonic germ line also exhibits unique and dynamic aspects of chromatin
      regulation, with chromosome-wide regulation particularly evident on the X
      chromosome. Several properties of X-specific chromatin assembly are also sex
      specific. These properties appear to be responding to the meiotic pairing status
      of the X chromosome, rather than the sex of the germ cells. Finally, gamete
      specific chromatin regulation during gametogenesis impacts on X chromatin
      assembly in the offspring, leading to an apparent sperm-imprinted X inactivation
      in the early embryo. Other potential roles for germline-specific modes of
      chromatin assembly in genome regulation and protection are discussed.

PMID- 18050478
TI  - Spermatogenesis.
AB  - Spermatogenesis creates functional sperm from an initially undifferentiated germ
      cell. In the nematode Caenorhabditis elegans, both males and hermaphrodites
      engage in spermatogenesis. The hermaphrodite germ line, like that of the male,
      initiates spermatogenesis during the L4 larval stage. The hermaphrodite germ line
      differs from that of the male because it ceases spermatogenesis and switches to
      oogenesis during the adult stage. Each hermaphrodite stores her sperm and uses
      them to fertilize her oocytes. Many mutants have been identified where
      hermaphrodite self-fertility is disrupted. If such a self-sterile hermaphrodite
      is mated to a wild-type male, mutant hermaphrodites that either lack sperm or
      contain defective sperm will produce outcross progeny. Easily implemented tests
      are then applied to identify the subset of these mutants that produce defective
      sperm. Currently, more than 44 genes are known that are required for normal
      spermatogenesis. This chapter discusses the 25 best-understood genes that affect
      spermatogenesis and mutants are grouped based on the cellular structure or
      process that is affected. C. elegans spermatozoa lack an acrosome and a
      flagellum, which are organelles found in the spermatozoa produced by most other
      species. Like other nematodes, C. elegans spermatozoa move by crawling using a
      single pseudopod. Wild-type spermatogenesis and its defects in mutants can be
      studied in vivo because the animal is transparent and in vitro because a simple,
      chemically defined medium that supports development has been discovered. Unlike
      nearly all other C. elegans cells, homogeneous sperm can be obtained in
      sufficient quantities to permit biochemical analyses.

PMID- 18050479
TI  - Somatic sex determination.
AB  - C. elegans occurs in two natural sexes, the XX hermaphrodite and the XO male,
      which differ extensively in anatomy, physiology, and behavior. All somatic
      differences between the sexes result from the differential activity of a "global"
      sex determination regulatory pathway. This pathway also controls X chromosome
      dosage compensation, which is coordinated with sex determination by the action of
      the three SDC proteins. The SDC proteins control somatic and germline sex by
      transcriptional repression of the her-1 gene. HER-1 is a secreted protein that
      controls a regulatory module consisting of a transmembrane receptor, TRA-2, three
      intracellular FEM proteins, and the zinc finger transcription factor TRA-1. The
      molecular workings of this regulatory module are still being elucidated.
      Similarity of TRA-2 to patched receptors and of TRA-1 to GLI proteins suggests
      that parts of the global pathway originally derived from a Hedgehog signaling
      pathway. TRA-1 controls all aspects of somatic sexual differentiation, presumably
      by regulating a variety of tissue- and cell-specific downstream targets,
      including the cell death regulator EGL-1 and the male sexual regulator MAB-3. Sex
      determination evolves rapidly, and conservation of sexual regulators between
      phyla has been elusive. An apparent exception involves DM domain proteins,
      including MAB-3, which control sexual differentiation in nematodes, arthropods,
      and vertebrates. Important issues needing more study include the detailed
      molecular mechanisms of the global pathway, the identities of additional sexual
      regulators acting in the global pathway and downstream of TRA-1, and the
      evolutionary history of the sex determination pathway. Recently developed genetic
      and genomic technologies and comparative studies in divergent species have begun
      to address these issues.

PMID- 18050480
TI  - Hermaphrodite cell-fate specification.
AB  - There are two sexes in C. elegans, hermaphrodite and male. While there are many
      sex-specific differences between males and hermaphrodites that affect most
      tissues, the basic body plan and many of its structures are identical. However,
      most structures required for mating or reproduction are sexually dimorphic and
      are generated by sex-specific cell lineages. Thus to understand cell fate
      specification in hermaphrodites, one must consider how the body plan, which is
      specified during embryogenesis, influences the fates individual cells. One
      possible mechanism may involve the asymmetric distribution of POP-1/Tcf, the sole
      C. elegans Tcf homolog, to anterior-posterior sister cells. Another mechanism
      that functions to specify cell fates along the anterior-posterior body axis in
      both hermaphrodites and males are the Hox genes. Since most of the cell fate
      specifications that occur in hermaphrodites also occur in males, the focus of
      this chapter will be on those that only occur in hermaphrodites. This will
      include the cell fate decisions that affect the HSN neurons, ventral hypodermal P
      cells, lateral hypodermal cells V5, V6, and T; as well as the mesodermal M, Z1,
      and Z4 cells and the intestinal cells. Both cell lineage-based and cell-signaling
      mechanisms of cell fate specification will be discussed. Only two direct targets
      of the sex determination pathway that influence cell fate specification to
      produce hermaphrodite-specific cell fates have been identified. Thus a major
      challenge will be to learn additional mechanisms by which the sex determination
      pathway interacts with signaling pathways and other cell fate specification genes
      to generate hermaphrodite-specific cell fates.

PMID- 18050481
TI  - Sperm motility and MSP.
AB  - Form follows function, and this maxim is particularly true for the nematode sperm
      cell. Motility is essential for fertilization, and the process of spermatogenesis
      culminates in the production of a crawling spermatozoon with an extended
      pseudopod. However, the morphological similarity to amoeboid cells of other
      organisms is not conserved at the molecular level. Instead of utilizing the actin
      cytoskeleton and motor proteins, the pseudopod moves via the regulated assembly
      and disassembly of filaments composed of the major sperm protein (MSP). The
      current work reviews the structure and dynamics of MSP filament formation, the
      critical role of pH in MSP assembly, and the recent identification of components
      that regulate this process. The combination of cytological, biochemical, and
      genetic approaches in this relatively simple system make nematode sperm an
      attractive model for investigating the mechanics of amoeboid cell motility.

PMID- 18050482
TI  - Epithelial junctions and attachments.
AB  - A distinctive feature of polarized epithelial cells is their specialized
      junctions, which contribute to cell integrity and provide platforms to
      orchestrate cell shape changes. The chapter discusses the composition and
      assembly of C. elegans cell-cell and cell-extracellular matrix junctions,
      proteins that anchor the cytoskeleton and mechanisms involved in establishing
      epithelial polarity. The focus remains cellular and does not properly deal with
      epithelial cells in the context of the developing embryo.

PMID- 18050483
TI  - Sarcomere assembly in C. elegans muscle.
AB  - Sarcomeres within body wall muscle in C. elegans include attachments to the
      sarcolemma that are remarkably similar in structure to vertebrate adhesion
      complexes. Crucial early steps in muscle sarcomere assembly, a highly
      orchestrated affair involving many proteins, involve the assembly of these
      sarcomere attachments. The steps involved in initiating the correct placement of
      these attachments and other sarcomere substructures are poorly understood. Using
      mutants in C. elegans we are attempting to dissect the various steps in this
      process. We review what has been discovered to date and present a model of
      sarcomere assembly that initiates at the plasma membrane and involves proteins
      within muscle, the hypodermis and within the extracellular matrix.

PMID- 18050484
TI  - Cell division.
AB  - The C. elegans embryo is a powerful model system for studying the mechanics of
      metazoan cell division. Its primary advantage is that the architecture of the
      syncytial gonad makes it possible to use RNAi to generate oocytes whose cytoplasm
      is reproducibly (typically >95%) depleted of targeted essential gene products via
      a process that does not depend exclusively on intrinsic protein turnover. The
      depleted oocytes can then be analyzed as they attempt their first mitotic
      division following fertilization. Here we outline the characteristics that
      contribute to the usefulness of the C. elegans embryo for cell division studies.
      We provide a timeline for the first embryonic mitosis and highlight some of its
      key features. We also summarize some of the recent discoveries made using this
      system, particularly in the areas of nuclear envelope assembly/dissassembly,
      centrosome dynamics, formation of the mitotic spindle, kinetochore assembly,
      chromosome segregation, and cytokinesis.

PMID- 18050485
TI  - Intracellular trafficking.
AB  - Studies in C. elegans have begun to reveal new components and new mechanisms
      associated with intracellular membrane traffic in a variety of cell types. The
      worm benefits from many of the advantages of yeast as a genetically tractable
      organism for these kinds of studies while offering the unique opportunity to
      probe how these pathways have been extended and modified in the context of a
      multicellular animal undergoing development to produce diverse cell types such as
      muscles, nerves, and polarized epithelia. This review summarizes recent work
      elucidating endocytic pathways, primarily in the worm germ line and coelomocytes,
      and also touches on diverse studies of secretion, especially in ectodermal cells
      of epithelial character.

PMID- 18050486
TI  - Cell fusion.
AB  - Selective cell fusion is a natural part of development. It is found in sexually
      reproducing organisms that require fertilization to propagate and in muscles,
      placenta, bones, lens of the eye and stem cells. Cell fusion is particularly
      important in the development of C. elegans: in addition to 300 sperm and oocytes
      that fuse during fertilization, 300 of the 1090 somatic cells born, fuse
      throughout development. Studies of cell fusion in C. elegans have shown that
      although different types of cells fuse, cell membrane merger is initiated through
      a common mechanism involving the action of one gene, eff-1. In worms with
      mutations that inactivate eff-1, almost none of the 300 somatic cells that
      normally fuse do so, but appear to differentiate, attach and behave in the same
      way as fusing cells. Such worms develop and survive but have numerous
      morphological, behavioral and fertility defects associated to cell fusion failure
      in the epidermis, pharynx, male tail, vulva and uterus. Cell fusion in embryonic
      dorsal epithelial cells has been analyzed in great detail by confocal microscopy
      using membrane fluorescent probes, apical junction markers and cytoplasmic
      aqueous fluorescent probes allowing the direct observation of membrane
      disappearance, pore expansion and cytoplasmic content mixing. The complete
      elimination of the membranes between two fusing cells takes about 30 min and
      involves vesiculation of the fusing membranes. Genetic and cell biological
      evidence indicates that eff-1 activity is both necessary and sufficient to fuse
      epithelial and myoepithelial cells in vivo. Based on electron microscopic
      analyses of intermediates of cell fusion in eff-1 mutants, it appears that eff-1
      is required for both initiation and expansion of fusion pores, similar to the
      fusogen of Influenza virus. While only one gene encoding a novel candidate
      component of the cell membrane fusion machinery has been found, the nematode's
      cell fusion program is under the control of many cell-specific transcriptional
      regulators. A large number of these conserved regulators prevent cell fusion by
      repressing eff-1 activity. For example, if either ceh-16/engrailed or the GATA
      factor EGL-18/ELT-5 is inactivated, the lateral epidermal cells that normally do
      not fuse in the embryo will fuse causing embryonic lethality. And if either the
      Hox protein lin-39/Deformed or its cofactor ceh-20/Extradenticle is inactivated,
      the ventral epidermal vulval precursor cells that normally do not fuse in the
      larvae will fuse and the hermaphrodite will have no vulva. In addition, there is
      evidence for coordinated and complex regulation of lin-39 in the ventral
      epidermis by Ras, Wnt, Rb/E2F, NuRD and lin-15 pathways. It appears that in many
      cells that normally do not fuse, specific transcription complexes repress eff-1
      expression preventing cell fusion. ref-2 (REgulator of Fusion-2) encodes a Zn
      finger protein that is required to generate ventral Pn.p cells and to keep them
      unfused both in males and hermaphrodites. ref-2 is necessary, but not sufficient,
      to maintain Pn.p cells unfused. This review shows that far from cell fusion being
      an unusual phenomenon, there is the clear prospect that animal cells in all
      tissues are intrinsically programmed to fuse, and are only prevented from fusing
      by transcriptional and post-transcriptional control mechanisms. There are three
      major questions that remain open for future research: (1) How does eff-1 fuse
      cells? (2) How do Ras, Wnt, Rb, NuRD, E2F, heterochronic and other pathways
      control cell fusion? (3) What are the implications of cell fusion beyond worms?

PMID- 18050487
TI  - RNA-binding proteins.
AB  - The C. elegans genome encodes many RNA-binding proteins (RBPs) with diverse
      functions in development, indicative of extensive layers of post-transcriptional
      control of RNA metabolism. A number of C. elegans RBPs have been identified by
      forward or reverse genetics. They tend to display tissue-specific mutant
      phenotypes, which underscore their functional importance. In addition, several
      RBPs that bind regulatory sequences in the 3'untranslated regions of mRNAs have
      been identified molecularly. Most C. elegans RBPs are conserved throughout
      evolution, suggesting that their study in C. elegans may uncover new conserved
      biological functions. In this review, we primarily discuss RBPs that are
      associated with well-characterized mutant phenotypes in the germ line, the early
      embryo, or in somatic tissues. We also discuss the identification of RNA targets
      of RBPs, which is an important first step to understand how an RBP controls C.
      elegans development. It is likely that most RBPs regulate multiple RNA targets.
      Once multiple RNA targets are identified, specific features that distinguish
      target from non-target RNAs and the type(s) of RNA metabolism that each RBP
      controls can be determined. Furthermore, one can determine whether the RBP
      regulates all targets by the same mechanism or different targets by distinct
      mechanisms. Such studies will provide insights into how RBPs exert coordinate
      control of their RNA targets, thereby affecting development in a concerted
      fashion.

PMID- 18050488
TI  - Mechanism and regulation of translation in C. elegans.
AB  - C. elegans represents a favorable system to study the extraordinarily complicated
      process of eukaryotic protein synthesis, which involves over 100 RNAs and over
      200 polypeptides just for the core machinery. Initial research in protein
      synthesis relied on fractionated mammalian and plant systems, but in the mid
      1970s, the powerful genetics of Saccharomyces cerevisiae began to yield new
      insights for translation in all eukaryotes. C. elegans has many features of
      higher eukaryotes that are not shared by yeast. This allows protein synthesis
      researchers to combine biochemistry, cell biology, developmental biology,
      genetics, and genomics to study regulation of gene expression at the
      translational level. Most components of the core translational machinery have
      been identified in C. elegans, including rRNAs, 5S RNA, tRNAs, ribosomal
      proteins, and aminoacyl tRNA synthetases. C. elegans has amino acid sequence
      homologs for 56 of the known initiation, elongation, and release factor
      polypeptides, but few of these have been isolated, functionally identified, or
      studied at the biochemical level. Similarly, C. elegans has homologs for 22
      components of the major signal transduction pathways implicated in control of
      protein synthesis. The translational efficiency of individual mRNAs relies on cis
      regulatory elements that include either a 7-methylguanosine- or 2,2,7
      trimethylguanosine-containing cap, the 5'-terminal spliced leader, sequence
      elements in the 3'-untranslated regions, and the 3'-terminal poly(A) tract.
      Several key developmental pathways in C. elegans are predominantly governed by
      translational mechanisms. Some evidence has been presented that well described
      regulatory mechanisms in other organisms, including covalent modification of
      translation factors, sequestration of translation factors, and mRNA-specific
      changes in poly(A) length, also occur in C. elegans. The most interesting
      unexplored questions may involve changes in the translation of individual mRNAs
      during development, in response to physiological changes, or after genetic
      manipulations. Given the highly developed state of C. elegans genomics, it can be
      expected that future application of computational tools, including data
      visualization, will help detect new instances of translational control.

PMID- 18050489
TI  - DNA repair.
AB  - The integrity of the genome is essential to the health of the individual and to
      the reproductive success of a species. Transmission of genetic information is in
      a selective balance between two opposing forces, the maintenance of genetic
      stability versus elimination of mutational change and loss of evolutionary
      potential. Caenorhabditis elegans provides many advantages for the study of DNA
      surveillance and repair in a multicellular organism. Several genes have been
      identified by mutagenesis and RNA interference that affect DNA damage checkpoint
      and repair functions. Many of these DNA damage response genes also play essential
      roles in DNA replication, cell cycle control, development, meiosis and mitosis.
      To date, no obvious DNA damage-induced checkpoint has been described in C.
      elegans somatic cells. In contrast, the DNA damage response in the germ line is
      characterized by two spatially separate checkpoints; mitotic germ nuclei
      proliferation arrest and apoptosis of damaged meiotic nuclei. Both of these
      responses are regulated by checkpoint genes including mrt-2, hus-1, rad-5 and cep
      1, the C. elegans ortholog of the human tumour suppressor p53. The germ line DNA
      damage checkpoints in C. elegans provide an excellent model in which to study the
      genes required to maintain genomic stability and to test compounds which might
      have tumor suppressing properties. In addition to single gene studies,
      integration of data from high-throughput screens has identified genes not
      previous implicated in the DNA damage response and elucidated novel connections
      between the different repair pathways. Most of the genes involved are conserved
      between worms and humans, and in humans, are associated with either oncogenesis
      or tumor-suppression. Thus, studies of the physical and functional interactions
      of the components of the repair pathways in C. elegans will provide information
      about human repair disorders and cancer predisposition.

PMID- 18050490
TI  - Pristionchus pacificus.
AB  - In the last decade, nematodes other than C. elegans have been studied intensively
      in evolutionary developmental biology. A few species have been developed as
      satellite systems for more detailed genetic and molecular studies. One such
      satellite species is the diplogastrid nematode Pristionchus pacificus. Here, I
      provide an overview about the biology, phylogeny, ecology, genetics and genomics
      of P. pacificus.

PMID- 18050491
TI  - Strongyloides spp.
AB  - Strongyloides is a genus of parasitic nematodes, which, unusually, has a free
      living adult generation. Here we introduce the biology of this genus, especially
      the fascinating, but complex, life-cycle together with an overview of the
      taxonomy, morphology, genetics and genomics of this genus.

PMID- 18050492
TI  - C. elegans and volatile anesthetics.
AB  - The mechanism of action of volatile anesthetics remains an enigma, despite their
      worldwide use. The nematode C. elegans has served as an excellent model to
      unravel this mystery. Genes and gene sets that control the behavior of the animal
      in volatile anesthetics have been identified, using multiple endpoints to mimic
      the phenomenon of anesthesia in man. Some of these studies have clear
      translational implications in more complicated organisms.

PMID- 18050493
TI  - Genomics and biology of the nematode Caenorhabditis briggsae.
AB  - The soil nematode Caenorhabditis briggsae is an attractive model system for
      studying evolution of both animal development and behavior. Being a close
      relative of C. elegans, C. briggsae is frequently used in comparative studies to
      infer species-specific function of the orthologous genes and also for studying
      the dynamics of chromosome evolution. The genome sequence of C. briggsae is
      valuable in reverse genetics and genome-wide comparative studies. This review
      discusses resources and tools, which are currently available, to facilitate study
      of C. briggsae in order to unravel mechanisms of gene function that confer
      morphological and behavioral diversity.

PMID- 18050494
TI  - Roles of chromatin factors in C. elegans development.
AB  - It is now well established that cells modify chromatin to establish
      transcriptionally active or inactive chromosomal regions. Such regulation of the
      chromatin structure is essential for the proper development of organisms. C.
      elegans is a powerful organism for exploring the developmental role of chromatin
      factors and their regulation. This chapter presents an overview of recent studies
      on chromatin factors in C. elegans with a description of their key roles in a
      variety of cellular and developmental processes.

PMID- 18050495
TI  - The C. elegans intestine.
AB  - The intestine is one of the major organs in C. elegans and is largely responsible
      for food digestion and assimilation as well as the synthesis and storage of
      macromolecules. In addition, the intestine is emerging as a powerful experimental
      system in which to study such universal biological phenomena as vesicular
      trafficking, biochemical clocks, stress responses and aging. The present chapter
      describes some of these many and varied properties of the C. elegans intestine:
      the embryonic cell lineage, intestine morphogenesis, structure and physiology of
      the intestinal cell and, finally, the transcription factor network controlling
      intestine development and function.

PMID- 18050496
TI  - Obesity and the regulation of fat metabolism.
AB  - As in all living organisms, survival in C. elegans requires adequate management
      of energy supplies. Genetic screens have revealed that C. elegans fat regulation
      involves a complex network of genes with known or likely functions in food
      sensation, neuroendocrine signaling, uptake, transport, storage and utilization
      of fats. Core fat and sugar metabolic pathways are conserved in C. elegans. Flux
      through these pathways is modulated by cellular energy sensors that operate via
      transcriptional and translational regulatory mechanisms. In turn, neuroendocrine
      mechanisms couple sensory and metabolic pathways while neuromodulatory pathways
      influence both metabolic and food seeking/consumption pathways. The shared
      ancestry of C. elegans and mammalian fat regulatory pathways extends to
      developmental programs that underlie fat storage capacity, despite lack of
      dedicated adipocytes, and genes whose human homologs are implicated in obesity.
      This suggests that many of the newly identified C. elegans fat regulatory
      pathways play similar roles in mammals. C. elegans is ideally suited for the
      integrated study of mechanisms that operate in multiple tissues and elicit
      feedback responses that affect processes as diverse as metabolism and behavior.

PMID- 18050497
TI  - The cuticle.
AB  - The nematode cuticle is an extremely flexible and resilient exoskeleton that
      permits locomotion via attachment to muscle, confers environmental protection and
      allows growth by molting. It is synthesised five times, once in the embryo and
      subsequently at the end of each larval stage prior to molting. It is a highly
      structured extra-cellular matrix (ECM), composed predominantly of cross-linked
      collagens, additional insoluble proteins termed cuticlins, associated
      glycoproteins and lipids. The cuticle collagens are encoded by a large gene
      family that are subject to strict patterns of temporal regulation. Cuticle
      collagen biosynthesis involves numerous co- and post-translational modification,
      processing, secretion and cross-linking steps that in turn are catalysed by
      specific enzymes and chaperones. Mutations in individual collagen genes and their
      biosynthetic pathway components can result in a range of defects from abnormal
      morphology (dumpy and blister) to embryonic and larval death, confirming an
      essential role for this structure and highlighting its potential as an ECM
      experimental model system.

PMID- 18050498
TI  - Sex determination in the germ line.
AB  - Sexual identity is one of a few basic parameters that specify how development
      should proceed. Although sex determination has profound effects on many tissues,
      its most ancient and fundamental role is ensuring that some germ cells become
      sperm, and others become oocytes or eggs. Spermatocytes and oocytes are usually
      produced in male and female animals, respectively, but C. elegans is uniquely
      suitable for studying the control of these cell fates because both types of cells
      are made from a common pool of progenitors in XX hermaphrodites. Extensive
      genetic and molecular studies have shown that the sexual fate of germ cells in C.
      elegans is controlled by the same genes that regulate sexual identity in other
      parts of the animal. However, this regulatory pathway has additional features
      that are unique to the germ line. First, several genes, like the three fogs, act
      only in germ cells. Second, the three fem genes act in concert with targets of
      tra-1 to control germ cell fates, but do not act this way in the soma. Third,
      translational repression of tra-2 is essential for hermaphrodite spermatogenesis.
      Fourth, translational repression of fem-3 is needed for oogenesis. In this
      review, we present genetic and molecular models for how these processes work, and
      summarize the evidence upon which they are built.

PMID- 18050499
TI  - The biology and genome of Heterorhabditis bacteriophora.
AB  - Heterorhabditis bacteriophora is an entomopathogenic nematode (EPN) mutually
      associated with the enteric bacterium, Photorhabdus luminescens, used globally
      for the biological control of insects. Much of the previous research concerning
      H. bacteriophora has dealt with applied aspects related to biological control.
      However, H. bacteriophora is an excellent model to investigate fundamental
      processes such as parasitism and mutualism in addition to its comparative value
      to Caenorhabditis elegans. In June 2005, H. bacteriophora was targeted by NHGRI
      for a high quality genome sequence. This chapter summarizes the biology of H.
      bacteriophora in common and distinct from C. elegans, as well as the status of
      the genome project.

PMID- 18050500
TI  - Strongyloides stercoralis: a model for translational research on parasitic
      nematode biology.
AB  - Because of their free-living life cycle alternatives, Strongyloides and related
      nematode parasites may represent the best models for translating C. elegans
      science to the study of nematode parasitism. S. stercoralis, a significant
      pathogen of humans, can be maintained in laboratory dogs and gerbils. Biosafety
      precautions necessary for work with S. stercoralis, though unfamiliar to many C.
      elegans researchers, are straightforward and easily accomplished. Although
      specialized methods are necessary for large-scale culture of the free-living
      stages of S. stercoralis, small-scale cultures for experimental purposes may be
      undertaken using minor modifications of standard C. elegans methods. Similarly,
      the morphological similarities between C. elegans and the free-living stages of
      S. stercoralis allow investigational methods such as laser cell ablation and DNA
      transformation by gonadal microinjection to be easily adapted from C. elegans to
      S. stercoralis. Comparative studies employing these methods have yielded new
      insights into the neuronal control of the infective process in parasites and its
      similarity to regulation of dauer development in C. elegans. Furthermore, we have
      developed a practical method for transient transformation of S. stercoralis with
      vector constructs having various tissue- and cell-specific expression patterns
      and have assembled these into a modular vector kit for distribution to the
      community.

PMID- 18050501
TI  - Biogenic amine neurotransmitters in C. elegans.
AB  - Four biogenic amines: octopamine, tyramine, dopamine and serotonin act in C.
      elegans to modulate behavior in response to changing environmental cues. These
      neurotransmitters act at both neurons and muscles to affect egg laying,
      pharyngeal pumping, locomotion and learning. A variety of experimental approaches
      including genetic, imaging, biochemical and pharmacological analyses have been
      used to identify the enzymes and cells that make and release the amines and the
      cells and receptors that bind them. Dopamine and serotonin act through receptors
      and downstream signaling mechanisms similar to those that operate in the
      mammalian brain suggesting that C. elegans will provide a valuable model for
      understanding biogenic amine signaling in the brain.

PMID- 18050502
TI  - Acetylcholine.
AB  - Acetylcholine is the major excitatory neurotransmitter at nematode neuromuscular
      junctions, and more than a third of the cells in the C. elegans nervous system
      release acetylcholine. Through a combination of forward genetics, drug-resistance
      selections, and genomic analysis, mutants have been identified for all of the
      steps specifically required for cholinergic function. These include two enzymes,
      two transporters, and a bewildering assortment of receptors. Cholinergic
      transmission is involved, directly or indirectly, in many C. elegans behaviors,
      including locomotion, egg laying, feeding, and male mating.

PMID- 18050503
TI  - The C. elegans pharynx: a model for organogenesis.
AB  - The C. elegans foregut (pharynx) has emerged as a powerful system to study organ
      formation during embryogenesis. Here I review recent advances regarding cell-fate
      specification and epithelial morphogenesis during pharynx development. Maternally
      supplied gene products function prior to gastrulation to establish pluripotent
      blastomeres. As gastrulation gets under way, pharyngeal precursors become
      committed to pharyngeal fate in a process that requires PHA-4/FoxA and the Tbox
      transcription factors TBX-2, TBX-35, TBX-37 and TBX-38. Subsequent waves of gene
      expression depend on the affinity of PHA-4 for its target promoters, coupled with
      combinatorial strategies such as feed-forward and positive-feedback loops. During
      later embryogenesis, pharyngeal precursors undergo reorganization and a
      mesenchymal-to-epithelial transition to form the linear gut tube. Surprisingly,
      epithelium formation does not depend on cadherins, catenins or integrins. Rather,
      the kinesin ZEN-4/MKLP1 and CYK-4/RhoGAP are critical to establish the apical
      domain during epithelial polarization. Finally, I discuss similarities and
      differences between the nematode pharynx and the vertebrate heart.

PMID- 18050504
TI  - Gene expression changes associated with aging in C. elegans.
AB  - Great inroads into the understanding of aging have been made using C. elegans as
      a model system. Several genes have been identified that, when mutated, can extend
      lifespan. Yet, much about aging remains a mystery, and new technologies that
      allow the simultaneous assay of expression levels of thousands of genes have been
      applied to the question of how and why aging might occur. With correct
      experimental design and statistical analysis, differential gene expression
      between two or more populations can be obtained with high confidence. The ability
      to survey the entire genome in an unbiased way is a great asset for the study of
      complex biological phenomena such as aging. Aging undoubtedly involves changes in
      multiple genes involved in multiple processes, some of which may not yet be
      known. Gene expression profiling of wild type aging, and of strains with
      increased life spans, has provided some insight into potential mechanisms, and
      more can be expected in the future.

PMID- 18050505
TI  - The sensory cilia of Caenorhabditis elegans.
AB  - The non-motile cilium, once believed to be a vestigial cellular structure, is now
      increasingly associated with the ability of a wide variety of cells and organisms
      to sense their chemical and physical environments. With its limited number of
      sensory cilia and diverse behavioral repertoire, C. elegans has emerged as a
      powerful experimental system for studying how cilia are formed, function, and
      ultimately modulate complex behaviors. Here, we discuss the biogenesis,
      distribution, structures, composition and general functions of C. elegans cilia.
      We also briefly highlight how C. elegans is being used to provide molecular
      insights into various human ciliopathies, including Polycystic Kidney Disease and
      Bardet-Biedl Syndrome.

PMID- 18050506
TI  - Mistletoe in tumour therapy. Abstracts of the 4th Mistletoe Symposium, 8-10
      November 2007, Nonnweiler-Otzenhausen, Germany.

PMID- 18050508
TI  - [Abstracts of the 49th annual meeting of the Clinical Research Club of Quebec,
      September 20-22, 2007, Mont-Tremblant, Canada].

PMID- 18050507
TI  - Abstracts of the joint annual meeting of the Swiss Society of Anaesthesiologie
      and Reanimation and the Swiss Society of Intensive Medicine, November 1-3, 2007,
      Interlaken, Switzerland.

PMID- 18050510
TI  - [Abstracts of the annual meeting of the Ophthalmologists Society of Saxony, 26-27
      October 2007, Chemnitz].

PMID- 18050509
TI  - Abstracts from the 27th Annual Conference on Dialysis, February 18-20, 2007,
      Denver, Colorado, USA.

PMID- 18050511
TI  - Abstracts of the International Society of Haematology, Congress of the European
      and African Division, 29 August-2 September, 2007, Budapest, Hungary.

PMID- 18050512
TI  - Abstracts of the 29th Annual Meeting of the American Society for Bone and Mineral
      Research, September 16-19, 2007, Honolulu, Hawaii, USA.

PMID- 18050513
TI  - [More and more Cesarean sections in China].

PMID- 18050514
TI  - Progesterone and preterm birth.

PMID- 18050515
TI  - Isolated systolic hypertension in the elderly.

PMID- 18050516
TI  - Childhood leukaemia and socioeconomic status.

PMID- 18050517
TI  - DNA-programmed chemistry in rapid homogeneous assays for DNA and protein targets.

PMID- 18050518
TI  - Call to atheists.

PMID- 18050519
TI  - Headline matters:creation of artificial life.

PMID- 18050520
TI  - Sea-change riches.

PMID- 18050521
TI  - Q & A. Richard Vallee.

PMID- 18050522
TI  - Real-time label-free acoustic technology for rapid detection of Escherichia coli
      O157:H7.

PMID- 18050523
TI  - An innovative, flow-assisted, noncompetitive chemiluminescent immunoassay for the
      detection of pathogenic bacteria.

PMID- 18050524
TI  - Application of liquid chromatography-mass spectrometry technology for early
      detection of microalbuminuria in patients with kidney disease.

PMID- 18050525
TI  - Closing the gap: improving front-line clinician proficiency in epilepsy care.

PMID- 18050526
TI  - Standards of care and the burden of treatment failure in type 2 diabetes.
AB  - Despite the armamentarium of oral and injectable agents available for the
      treatment of type 2 diabetes, there is clearly a significant gap between current
      recommendations for glycemic targets and the proportion of patients who can
      achieve and maintain glycemic control. Early diagnosis and intervention,
      particularly with the initiation of insulin therapy, may delay the progressive
      loss of pancreatic beta cells and the risk for macrovascular and microvascular
      complications. While there are numerous myths and misconceptions surrounding
      insulin therapy, physician and patient education, as well as an awareness of
      cultural sensitivities, can be instrumental in overcoming these barriers.

PMID- 18050527
TI  - Contemplating complementary medicine?

PMID- 18050528
TI  - The impact of obesity on cardiometabolic risk.

PMID- 18050529
TI  - Hypertension within the cardiovascular disease risk paradigm.
AB  - Hypertension remains a significant health issue not only for Americans but for
      the worldwide population. Elevated BP can not only be controlled but can be
      prevented, by addressing modifiable risk factors for CVD, including increased
      body weight, physical inactivity, poor dietary habits, alcohol consumption, and
      smoking. The challenge for the clinician is to reduce the global risk for CVD by
      preventing or at least delaying the onset ofmodifiable CVD risk factors, and,
      when pharmacologic intervention is warranted, managing hypertension aggressively
      in order to help patients achieve recommended BP goals.

PMID- 18050530
TI  - Establishing sound goals for hypertension management.
AB  - There is a clear need to reduce the prevalence of hypertension and, therefore,
      cardiovascular risk, among Americans. Many are unaware they have elevated BP,
      less than half who have been diagnosed with hypertension are treated, and only a
      third of those treated reach recommended goals. While hypertension affects
      American men and women of many ethnicities, prevalences are notably increased
      among blacks and Hispanics. Merely adopting positive lifestyle changes that
      include more exercise, a healthy, low-sodium diet for weight reduction, and
      smoking cessation can significantly improve both systolic and diastolic BP When
      pharmacologic treatment is needed, several classes ofantihypertensive agents with
      differing mechanisms of action are available for use as monotherapy or in various
      combinations to help patients reach their BP goals. Often three or more
      antihypertensive drugs are necessary for adequate BP control; however, the
      antihypertensive regimen must be tailored to the individual patient. It is more
      meaningful to assess and understand the individual patient with hypertension in
      order to set realistic BP goals than to expect all patients to reach the same
      goal with a uniform therapeutic plan.

PMID- 18050531
TI  - Case studies: applying JNC-7 treatment guidelines.
AB  - Patients with hypertension often have other comorbidities, such as heart failure,
      diabetes, or CKD, that can complicate their clinical management. Controlling BP
      in these patients is key to reducing their overall risk for morbidity and
      mortality. Current recommendations indicate which classes of antihypertensive
      agents are appropriate for patients with cardiovascular, renal, and metabolic
      comorbidities. The recommendations are based on prospective, randomized clinical
      trials in specific patient populations that evaluated several classes of
      antihypertensives, including beta-blockers, ARBs, ACE inhibitors, and CCBs,
      administered as monotherapy or in various combinations. These cases illustrate
      the application of clinical trials evidence to the management of hypertension in
      clinical practice.

PMID- 18050532
TI  - [Internal medicine and internists in Germany. A historical sketch of the history
      of the German Society of Internal Medicine].

PMID- 18050533
TI  - Outbreak news. Rift Valley fever, Sudan--update.

PMID- 18050534
TI  - Progress in global measles control  and mortality reduction, 2000-2006.

PMID- 18050535
TI  - A place for women: a selective annotated bibliography on Civil War women in
      medical services.

PMID- 18050536
TI  - Surviving a flood.

PMID- 18050537
TI  - William James on an unseen order.

PMID- 18050538
TI  - Promoting civil rights through the welfare state: how Medicare integrated
      Southern hospitals.

PMID- 18050539
TI  - Questions diagnosis of frenulum of the epiglottis in racehorse.

PMID- 18050540
TI  - For the love of mustard.

PMID- 18050541
TI  - Educational Quiz. A painful gum.

PMID- 18050542
TI  - Charting the terrain of touch.
AB  - Discusses the Laboratory for Human and Machine Haptics at the Massachusetts
      Institute of Technology, nicknamed the Touch Lab, which investigates new
      technologies involved in the sense of touch.

PMID- 18050543
TI  - Professional practice. The peugeot led recovery.

PMID- 18050544
TI  - Shoulder pain.

PMID- 18050545
TI  - Malaria.

PMID- 18050546
TI  - Childless women in the plays of William Inge.

PMID- 18050547
TI  - "The best or none!" Spinsterhood in nineteenth-century New England.

PMID- 18050548
TI  - Rudolph Fisher: an updated selected bibliography.

PMID- 18050550
TI  - Monstrous productions or the best of womanhood? Progressive-Era women in
      medicine.

PMID- 18050551
TI  - Alcohol and temperance.

PMID- 18050552
TI  - Promoting clean water in nineteenth-century public policy: professors, preachers,
      and polliwogs in Kingston, Ontario.

PMID- 18050553
TI  - A note from the editor-in-chief.

PMID- 18050554
TI  - [Organogenesis in mammals: Introduction].

PMID- 18050555
TI  - ISOEAID '05 in Kumamoto. Towards the consecutive and comprehensive control
      measures for prevention of allergy and immuno-toxicity in the workplace and
      living environment. Preface.

PMID- 18050556
TI  - Sex, gender and condom use.

PMID- 18050557
TI  - Prevalence and risk factors of undetected elevated blood pressure in an elderly
      Southeast Asian population.
AB  - Data on the prevalence of Hypertension (HTN) among elderly Asians is limited. We
      investigated the prevalence of elevated blood pressure (EBP) and its risk factors
      in a multiracial Southeast Asian elderly population who participated in the
      National Kidney Foundation Singapore nationwide screening programme. Among 19,848
      subjects > or =65 years (approximately 6% of the total Singapore population), the
      mean age was 70.6 +/- 5.26 yrs. After excluding 36.6% with known HTN, analysis
      revealed that 5,889 (46.8%) of the remaining population had previously undetected
      EBP > 140/90. Increasing age, male gender, BMI > or =23 kg/m2 and pre-existing
      diabetes were significantly associated with previously undetected EBP on
      multivariate analysis. 6% of cases with undetected EBP had proteinuria suggestive
      of longstanding EBP and renal damage. We conclude that there is a high prevalence
      of undetected EBP in elderly Asians, suggesting the need for increased efforts in
      screening in the elderly population.

PMID- 18050558
TI  - Awareness and perception about tuberculosis in the general population of Delhi.
AB  - The present study was conducted to assess awareness and perception regarding
      tuberculosis among the general population of Delhi. A total of 1008 adults,
      selected by multistage stratified systematic sampling, were interviewed using a
      pre-tested proforma. The majority had heard about tuberculosis (99.1%) and most
      (89.2%) perceived it to be an infectious disease. The correct mode of
      transmission i.e. airborne (coughing/sneezing) was known to 71.8% study subjects.
      The majority (90.1%) knew cough as a symptom. Nearly all (98.2%) perceived
      Tuberculosis to be a preventable disease, citing the treatment of patients as the
      mainstay of preventing spread of the disease. However, responses like separation
      of utensils or hospitalisation of the patient to prevent the spread of the
      disease indicate persistence of stigma and discrimination in a small proportion
      of the population. There is a need to widen the scope and intensify the
      information and education being provided to the population based on gaps
      identified.

PMID- 18050559
TI  - Exploring the economics of motorcycle helmet laws--implications for low and
      middle-income countries.
AB  - This paper reviews economic evaluations of motorcycle helmet interventions in
      preventing injuries. A comprehensive literature review focusing on the
      effectiveness of motorcycle helmet use, and on mandatory helmet laws and their
      enforcement was done. When helmet laws were lifted between 1976-80, 48 states
      within the U.S.A. experienced a cost of $342,047 per excess fatality of annual
      net savings. Helmet laws in the USA had a benefit-cost ratio of 1.33 to 5.07.
      Taiwan witnessed a 14% decline in motorcycle fatalities and a 22% reduction of
      head injury fatalities with the introduction of a helmet law. In Thailand, where
      70-90% of all crashes involve motorcycle, after enforcement of a helmet law,
      helmet-use increased five-fold, the number of injured motorcyclists decreased by
      33.5%, head injuries decreased by 41.4%, and deaths decreased by 20.8%. There is
      considerable evidence that mandatory helmet laws with enforcement alleviate the
      burden of traffic injuries greatly. For low and middle-income countries with high
      rates of motorcycle injuries, enforced, mandatory motorcycle helmet laws are
      potentially one of the most cost-effective interventions available.

PMID- 18050560
TI  - Relationship between reproductive exposures and age-related cataract in women.
AB  - The objective of this study is to evaluate the relationship between reproductive
      exposures and age-related cataract among women. This was a hospital based case
      control study. The study population included female patients, aged 50 years and
      above who attended the Eye clinic at the University of Malaya Medical Centre. The
      outcome measurement was based on ophthalmologic examination by an
      ophthalmologist. The data on exposure was obtained from face to face interview
      using a structured questionnaire. In order to reduce the recall bias, patients'
      medical records were used to substantiate the exposure status. Multiple logistic
      regression was used to assess the association of age-related cataract with
      exogenous estrogen usage (HRT and OCP) and duration of menses. Important
      confounders such as age, history of diabetes, cigarette smoking and steroids
      usage were controlled for in the analysis. Females with 29 years or less of
      endogenous estrogen exposure of, have almost three times the risk of developing
      age related cataract (adjusted OR 3.42: 95% CI: 1.28, 9.16), similarly among
      those with exposure of 30-32 years (adjusted OR 3.64: 95% CI: 1.08, 12.26).
      Hormone Replacement Therapy used for more than three years was found to be a
      protective factor of age-related cataract. There is evidence that reproductive
      exposure may play a role in reducing the occurrence of age-related cataract among
      Malaysian women.

PMID- 18050561
TI  - Factors associated with inappropriate utilisation of emergency department
      services.
AB  - This study was carried out to determine the associated factors and the reasons
      for inappropriate utilisation of Emergency Department (ED) services at Universiti
      Sains Malaysia Hospital. A case-control study was conducted with 170 cases from
      ED and 170 controls from the Outpatient Department (OPD). A self-administered
      questionnaire was designed and used to obtain sociodemographic data, knowledge on
      the functions of ED and OPD, health seeking attitude and behaviour, and reasons
      for seeking treatment at ED. The study found that gender, marital status, family
      size, shift work, perceived illness, and knowledge on the role and functions of
      ED and OPD were significant associated factors. The three most common reasons for
      inappropriate utilisation of ED were as follows: "due to severity of illness"
      (85%), "can't go to OPD during office hours" (42%), and "ED near my house" (27%).

PMID- 18050562
TI  - Economic disparity and child survival in Cambodia.
AB  - Despite improvements in child survival in recent decades, levels of infant and
      child mortality remain unacceptably high, particularly among the poor in
      developing countries recovering from recent wars and civil unrests. Using
      information on 8498 childbirths in five years preceding the 2000 Cambodia
      Demographic and Health Survey, this study measured the association between
      economic disparity and infant mortality using multivariate Weibull regression.
      Results indicate that children born in the poorest 40% households were more than
      twice as likely to die during infancy as those born in the richest 20%
      households, even after controlling for pregnancy care, birth weight, household
      living conditions, and other factors. Children born in the middle-income
      households also had significantly higher mortality risks. Not receiving antenatal
      care and low birth weight were associated with an increased risk. Also, boys had
      a higher risk than girls. The study concludes that poverty is strongly negatively
      associated with infant survival in Cambodia.

PMID- 18050563
TI  - Gender differences in sexual behavior and condom-related behaviours and attitudes
      among Korean youths.
AB  - We examined gender differences in sexual behaviours, condom-related behaviours
      and attitudes to premarital sex in order to identify gender differences in young
      Korean singles aged 19 to 30 years. This study was based on data from the 2003
      national survey of attitudes and behaviours towards AIDS in the Korean adult
      population, which contains information on a national sample of the general
      population aged 19 to 59 years. We selected 501 unmarried subjects between the
      ages of 19-30 from 1995 respondents. The selection criterion for the subjects'
      age was based on the 2003 Korean mean age for marriage which was 29.8 for men and
      27.0 for women. Gender differentials in sexual behaviour, condom use and related
      attitudes toward condom use were assessed. Although men initiated sexual practice
      earlier and had more multiple partners than women, both genders were equally
      likely to have engaged in inconsistent condom use, even when having sex with a
      high risk partner. These findings suggest that sex education focusing on condom
      use should be included in the school curricula. Implementation of early sexual
      education should start before the students initiate sexual activity to give them
      a chance to prepare gradually.

PMID- 18050564
TI  - Trends in olive pollen allergy. Introduction.

PMID- 18050565
TI  - Olive pollen recombinant allergens: value in diagnosis and immunotherapy.
AB  - Olive pollen has a complex allergenic profile, from which more than 10 allergens
      have been identified and characterized. Some of these belong to well-known
      protein families and others cannot be included in reported biochemical types.
      Most of these allergens have been produced by recombinant technology, mainly in
      Escherichia coli or in Pichia pastoris, and they are good candidates for
      diagnostic and therapeutic purposes. Diagnosis and immunotherapy of allergy
      currently use extracts prepared from homogenates of natural sources, which only
      allow us to detect sensitivity to the complete source. These extracts can be
      successfully replaced by mixtures with controlled amounts of specific allergenic
      proteins obtained by recombinant technology in order to define the sensitization
      profile of individual patients. Recombinant Ole e 1 can be used as a marker for
      sensitization to Oleaceae. Recombinants Ole e 2 (profilin) and Ole e 3
      (polcalcin) can serve as markers of polysensitivity. Finally, recombinant forms
      of Ole e 6, Ole e 10, and the carboxy-terminal and amino-terminal domains of Ole
      e 9 would help to detect sensitization to these minority allergens that could be
      overlooked in the complete olive pollen extract. These recombinant molecules can
      help provide an accurate diagnosis of sensitivity to individual allergens and,
      therefore, improve the design of more efficacious allergen-based immunotherapy
      strategies.

PMID- 18050566
TI  - Degree of olive pollen exposure and sensitization patterns. Clinical
      implications.
AB  - BACKGROUND: Very high levels of exposure to olive pollen in the south of Spain
      lead to differential allergen sensitization profiles. Therefore, new approaches
      to allergen standardization, diagnosis, and vaccination are necessary. METHODS:
      Quantification of minor allergens in extracts, component-resolved patient
      diagnosis, and IgG4 individual allergen responses were used to evaluate new
      strategies in the management of olive pollen allergy. RESULTS: Allergen
      variability observed between different olive cultivars can be used to identify
      suitable allergen sources that can be combined to yield consistent allergen
      extracts for diagnosis and immunotherapy. Component-resolved diagnosis can
      provide a better patient classification. IgG4 levels to major allergens increase
      significantly, whereas specific IgG4 to minor allergens does not seem to
      increase, at least during the early phases of immunotherapy. CONCLUSION: Patients
      exposed to extreme olive pollen levels display a different severity of allergy
      from those exposed to normal levels, which makes it necessary to follow a
      different clinical approach. The use of component-resolved diagnosis, better
      standardized allergen extracts, and new efficacy monitoring techniques will lead
      to a significant improvement in the management of olive allergy disease.

PMID- 18050567
TI  - Differential characteristics of olive pollen from different cultivars: biological
      and clinical implications.
AB  - The olive tree is grown in many parts of the world. Its germplasm is very broad,
      with 250 varieties in Spain alone. Variations in the ability of pollen to
      germinate have been studied in detail and show conspicuous differences between
      varieties. However, commercial olive pollen from cultivars whose origin is
      unknown is the material that is commonly used for clinical and biological
      studies. We aim to assess the putative heterogeneity of olive cultivars with
      regard to the presence of several pollen allergens and to determine whether these
      differences have biological and clinical relevance. Previous studies show that
      most allergens isolated and characterized to date are highly polymorphic. Olive
      cultivars display wide differences in the expression levels of many allergens and
      in the number and molecular characteristics of the allergen isoforms expressed.
      These differences are maintained over the years, and are intrinsic to the
      genetics of each cultivar. Such broad polymorphism seems to be involved in the
      physiology of the olive reproductive system, which might include the adaptation
      of the plant to different environmental conditions, the establishment of the
      compatibility system, and pollen performance. The differences in allergen
      composition in cultivars, particularly in the Ole e 1 allergen, are responsible
      for the important differences in the allergenic potency of the extracts. These
      findings could have a number of implications for the diagnosis and therapy of
      olive pollen allergy. We discuss how cultivar differences affect extract quality,
      diagnostic and therapeutic efficacy and safety, and the development of new
      vaccines based on the use of recombinant allergens.

PMID- 18050568
TI  - Modelling diseases: the allergens of Olea europaea pollen.
AB  - This study analyzes the influence of the IgE response to certain olive pollen
      allergens in the modulation of the different clinical phenotypes of allergic
      disease and their relationship with the level of exposure to pollen and genetic
      factors. Patients from high-exposure areas had a complex IgE antibody response to
      allergens of Olea euroapea, which included 3 or more allergens in 75% of cases.
      The majority allergens were Ole e 1, Ole e 2 (profilin), Ole e 7 (lipid
      transporting protein), Ole e 9 (glucanase), and Ole e 10. The existence of the
      antigen HLA-DR2 (15) led to a higher risk of sensitization to Ole e 10 and a
      greater trend towards the development of severe asthma, which increased in the
      presence of an anti-profilin IgE. Thirty percent of patients suffering from
      pollinosis simultaneously presented allergy to vegetable foods. Anti-Ole e 7 IgE
      was significantly associated with fruit anaphylaxis and anti-profilin IgE was
      detected in 90% of patients with oral syndrome. Finally, we analyzed the role of
      glucanase and Ole e 10 as causes of the pollen-latex-fruit syndrome.

PMID- 18050569
TI  - Modulation of allergic response by gene-environment interaction: olive pollen
      allergy.
AB  - This article summarizes the most important advances of recent years in the field
      of gene-environment interaction in allergic response. It specifically examines
      sensitization to olive pollen as an example of one of the main causes of allergic
      disease in the Mediterranean area. The presence of at least 20 proteins with
      allergic activity has been demonstrated in olive pollen, and 10 of these have
      been characterized (Ole e 1 to Ole e 10). Ole e 1, which is considered to be the
      majority allergen (causing sensitization in more than 70% of patients), has been
      the subject of many studies looking for risk factors and ways to protect against
      sensitization. Markers of the major histocompatibility complex and other genetic
      loci associated with the allergic response have been analyzed using population
      based, family-based, and functional approaches, which have revealed the
      involvement of genetic regulation in this type of response. Furthermore,
      evaluation of environmental factors and their relationship with genetic factors
      is essential when attempting to understand this type of disease. In this review,
      we provide examples of how exposure to high doses of olive pollen allergen in a
      specific genetic context can trigger different allergic conditions (from asthma
      to nonresponse). We stress the importance of evaluating these factors in order to
      modulate this response correctly.

PMID- 18050570
TI  - Component-resolved diagnosis to optimize allergen-specific immunotherapy in the
      Mediterranean area.
AB  - Allergen-specific immunotherapy (SIT) is the only allergen-specific treatment for
      allergy. It can prevent progression of the disease and has a long-lasting
      therapeutic effect. Since SIT is allergen-specific, the identification of the
      disease-eliciting allergen is an essential prerequisite for the accurate
      prescription of treatment. Diagnostic tests based on allergen extracts consist of
      mixtures of various allergens of which some are specific for the allergen source
      and others occur as cross-reactive allergens in various unrelated allergen
      sources. It may therefore be difficult and sometimes impossible to identify the
      disease-causing allergen with such tests, particularly in patients who are
      sensitized to more than one allergen source. Sensitization to pollens from olive,
      grasses, and Parietaria in the Mediterranean area is frequently treated with SIT.
      Here, we describe allergen molecules from these sources that can be used for
      component-resolved diagnosis of allergy to facilitate the selection of patients
      for SIT and monitor the immunological effects of treatment.

PMID- 18050571
TI  - Pla 1 1 and Ole e 1 pollen allergens share common epitopes and similar
      ultrastructural localization.
AB  - BACKGROUND: English plantain (Plantago lanceolata L.) and olive (Olea europaea
      L.) pollens are important causes of pollinosis in large areas of North America,
      Australia, and the Mediterranean basin. The major pollen allergens of both
      plants, Pla I 1 and Ole e 1, share 38.7% of their amino acid sequences.
      OBJECTIVE: To analyze putative cross-reactivity between these 2 proteins.
      METHODS: Several antibodies and patients' sera were used in immunoblot and
      immunocytochemistry experiments. RESULTS: Two anti-Pla I 1 antibodies were able
      to bind to 3 polypeptides from olive pollen protein extracts, which correspond to
      the 3 glycosylation isoforms of Ole e 1 (18-22 kDa) previously described.
      Moreover, Pla I 1 protein was found in the cytoplasm of both the vegetative and
      the generative cells of P lanceolata mature pollen. On olive pollen sections,
      these anti-Pla I 1 antibodies displayed significant labeling in the cytoplasm of
      the vegetative cell and in both the exine and the material adhering to this outer
      layer of the pollen wall. In addition, the anti-Ole e 1 antibody 10H1 was found
      to cross-react with proteins of similar masses (16-20 kDa) to Pla I 1 variants.
      In Plantago pollen sections, the 10H1 antibody recognized proteins located in the
      cytoplasm of both the vegetative and generative cells. Cross-reaction was
      confirmed using sera from patients allergic to either plant pollen. CONCLUSION:
      Both allergens share common epitopes, which can be cross-recognized by different
      antibodies and sera from different patients, although this antigenic similarity
      seems to have little clinical relevance.

PMID- 18050574
TI  - Caring for the person with special needs: a rewarding professional
      responsibility.

PMID- 18050573
TI  - Dental cements--are you confused?

PMID- 18050572
TI  - Are there any alternatives to alendronate (Fosamax) for osteoporosis to avoid the
      risk of osteonecrosis of the jaw?

PMID- 18050575
TI  - Aging patients: turning dental tragedies into triumphs. Transcript of a lecture
      presented on June 28 at the 2007 AGD Annual Meeting & Exhibits in San Diego.

PMID- 18050576
TI  - Combination of aspirin and clopidogrel for the prevention of thrombosis:
      implications for the dental practitioner.
AB  - The use of aspirin and clopidogrel as effective antiplatelet therapy in
      preventing secondary thromboembolic events is well-established. However, there is
      controversy among dentists and physicians regarding the appropriate dental
      management of patients receiving dual antiplatelet therapy due to the lack of
      clinical studies about hemorrhagic risk in these patients. Indications for
      modifying dual antiplatelet therapy--whether it is done by altering doses,
      switching to monotherapy, or discontinuing it completely--occur infrequently, as
      most patients can be treated in a dental office setting. In all cases, patients
      must be managed jointly by the dentist and physician, taking into account the
      patient's medical and dental history. This article reviews the current use of
      aspirin and clopidogrel as combination therapy, examining their effect on
      platelet function, the associated hemorrhagic risk during dental procedures for
      patients using this therapy, and how oral health care providers can manage these
      patients safely and effectively.

PMID- 18050577
TI  - Removal of the smear layer from flattened canals using different chemical
      substances.
AB  - This study used scanning electron microscopy to evaluate the flattened root
      canals of human mandibular incisors cleaned with nickel-titanium instruments and
      different chemical substances. Teeth were selected and divided randomly into five
      groups (n = 10) according to the chemical substances used in the biomechanical
      preparation: 5.25% sodium hypochlorite (Group 1), 5.25% sodium hypochlorite plus
      a final irrigation with 17% EDTAC (Group 2), EDTA gel combined with 5.25% sodium
      hypochlorite (Group 3), 2% chlorhexidine gel (Group 4), and 5.25% sodium
      hypochlorite combined with Glyde File Prep gel (Group 5). Data analysis showed a
      statistically significant difference (p < 0.001) among groups. Groups 1 and 5
      were similar statistically (p > 0.001) and displayed a higher amount of smear
      layer on canal walls. Samples from Groups 2, 3, and 4 revealed root canal walls
      without smear layer and exposed dentin tubules. Among the associations tested in
      this study, 5.25% sodium hypochlorite solution combined with 17% EDTAC, 5.25%
      sodium hypochlorite combined with EDTA gel, and 2% chlorhexidine gel all were
      effective substances for removing the smear layer from flattened root canals.

PMID- 18050578
TI  - The potential effects of pH and buffering capacity on dental erosion.
AB  - Soft drink pH (initial pH) has been shown to be a causative factor--but not
      necessarily the primary initiating factor--of dental erosion. The titratable
      acidity or buffering capacity has been acknowledged as playing a significant role
      in the etiology of these lesions. This in vitro study sought to evaluate five
      different soft drinks (Coca-Cola Classic, Diet Coke, Gatorade sports drink, Red
      Bull high-energy drink, Starbucks Frappucino coffee drink) and tap water
      (control) in terms of initial pH and buffering capacity. Initial pH was measured
      in triplicate for the six beverages. The buffering capacity of each beverage was
      assessed by measuring the weight (in grams) of 0.10 M sodium hydroxide necessary
      for titration to pH levels of 5.0, 6.0, 7.0, and 8.3. Coca-Cola Classic produced
      the lowest mean pH, while Starbucks Frappucino produced the highest pH of any of
      the drinks except for tap water. Based on statistical analysis using ANOVA and
      Fisher's post hoc tests at a P < 0.05 level of significance, Red Bull had the
      highest mean buffering capacity (indicating the strongest potential for erosion
      of enamel), followed by Gatorade, Coca-Cola Classic, Diet Coke, and Starbucks
      Frappucino.

PMID- 18050579
TI  - Transitory paresis of the lateral pterygoid muscle during a posterior superior
      alveolar nerve block--a case report.
AB  - The posterior superior alveolar nerve (PSAN) is a major sensory branch of the
      maxillary division of the trigeminal nerve. A PSAN block is a dental nerve block
      used for profound anesthesia of the maxillary molars. Complications arising from
      the PSAN block include hematoma formation, transient diplopia, blurred vision,
      and temporary blindness. This article presents a case of temporary paresis in the
      lateral pterygoid muscle following a PSAN block that utilized a 27-gauge long
      needle. The anatomical parameters and pathogenesis of such a complication are
      reviewed.

PMID- 18050580
TI  - Current role of thalidomide in HIV-positive patients with recurrent aphthous
      ulcerations.
AB  - Among patients with HIV/AIDS, mucosal lesions of unknown etiology such as
      recurrent aphthous ulcerations (RAUs) often are unresponsive to standard
      therapies, resulting in substantial morbidity. The literature regarding RAUs
      suggests that the inflammatory response contributes to its pathogenesis; however,
      the role of cytokines in this mucosal immune response remains largely unknown.
      Thalidomide first was marketed as a sedative in the 1950s and withdrawn from the
      market in 1961 following reports of teratogenicity. Later, it was used as an
      investigational agent for the treatment of Hansen's disease, Kaposi's sarcoma,
      myelofibrosis, RAUs, and wasting associated with HIV. Thalidomide's mechanism of
      action in RAUs still is not understood completely, but it appears to be mediated
      by inhibition of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF
      alpha). This article discusses the current status of thalidomide for treating
      RAUs in HIV-positive patients. Suggestions regarding the safe and effective
      prescribing of thalidomide have been included so that dental professionals will
      be able to treat these patients safely.

PMID- 18050581
TI  - Diagnosis and clinical management of patients with skeletal Class III dysplasia.
AB  - This paper summarizes the current literature on the diagnosis and treatment of a
      patient with Class III skeletal dysplasia. It also includes a report of two
      siblings with Class III skeletal dysplasia, although each received different
      treatment due to different causes of the condition. This review illustrates that
      early appropriate diagnosis, including cephalometric analysis, is important for
      identifying the location of the dysplasia. If the dysplasia is in the maxilla,
      treatment may prevent the need for future orthognathic surgery. Treatment for
      mandibular prognathism usually involves waiting for the patient's growth to
      complete (this could occur past the age of 18 in women and the age of 20 in men)
      and performing orthognathic surgery at that time.

PMID- 18050582
TI  - Flexible, removable partial denture for a patient with systemic sclerosis
      (scleroderma) and microstomia: a clinical report and a three-year follow-up.
AB  - This article describes an optional mode of treatment for a partially edentulous
      patient with severe microstomia, severe changes to the intraoral soft tissues,
      and compromised hand function. The principles discussed in this article describe
      a patient with systemic sclerosis but are applicable to any patient who suffers
      from scarring in the oral and facial areas due to disease, trauma, or burning
      injuries. Since dental implants were contraindicated, it was determined that long
      term comfort and function could be achieved only through the use of a removable
      partial denture (RPD). A Valplast flexible RPD was used because of its unique
      characteristics and a specially designed folded custom impression tray was used
      to obtain an accurate impression of hard and soft tissues. This article describes
      the complete process and management of the patient's needs, focusing on the
      decision-making process for the chosen treatment plan, the special impression
      technique, and the completion of the RPD.

PMID- 18050583
TI  - Demographic characteristics of general dental practice sites.
AB  - This study investigates the demographic characteristics of general dental
      practice sites in the United States and develops a model that identifies practice
      site characteristics commonly associated with general dental practices.
      Demographic data and general dental practices were organized by zip codes and
      analyzed using Discriminant Analysis. The demographic characteristics associated
      with zip codes that contained a general dental practice were determined. The
      resulting model correctly classified 85.2% of the 30,115 zip code areas, based on
      the presence or absence of a general dental practice. The variables most closely
      associated with a zip code containing a general dental practice included
      population size, age distribution of the population, educational background, and
      economic status. Demographic characteristics are predictive of sites with or
      without a general dental practice. Zip codes with large, urban populations that
      have positive socio-economic characteristics, such as high income and education
      levels, are the most likely to have a general dental practice. A significant
      number of zip codes in the U.S. (852) have the demographic characteristics
      associated with a general dental practice site but do not have a general dentist.

PMID- 18050584
TI  - Can jua be a weapon in combating oral diseases?
AB  - Jua (or Joazeiro) is a plant that has been used in Brazil as a folk remedy for
      many diseases, but mostly as a dentifrice. Several scientific investigations have
      been conducted in Brazil to examine the therapeutic use of Jua for oral health.
      This article presents information about the Ziziphus joazeiro plant, its
      medicinal use, and its chemical components while also reviewing the literature
      concerning Jua and especially its anti-plaque activity. Although Joazeiro has
      been investigated, more studies must be performed to better understand these Jua
      compounds, their antimicrobial activity, and their mechanism of action. Such
      studies would confirm whether Joazeiro has the potential to fight or prevent
      diseases like dental caries and periodontitis.

PMID- 18050585
TI  - Pharmacologic management of type 2 diabetes: a review for dentistry.
AB  - Over the last 40 years, diabetes mellitus has increased sixfold in the United
      States. Reported cases increased by more than 6.0% in 2006. Type 2 diabetes
      accounts for approximately 90% of all cases and is becoming more common in
      children and adolescents. The cause of Type 2 diabetes involves both genetic and
      environmental factors. The recent increase in the incidence and prevalence of
      Type 2 diabetes is related largely to obesity. Type 2 diabetes is managed by
      lifestyle interventions, drug therapy, and control of risk factors for
      cardiovascular disease. Patients with renal failure can be treated by
      transplantation of a kidney and pancreas. Islet cell transplantation is
      available, but long-term results have not been good. Pharmacologic treatment is
      accomplished with several classes of oral drugs. This article reviews the
      literature to provide recent innovations in the pharmacologic management of Type
      2 diabetes mellitus.

PMID- 18050586
TI  - Tobacco use in a dental school patient population.
AB  - A retrospective study was performed to determine the incidence of tobacco usage
      and cessation in a dental school patient population. The study was conducted to
      assess the magnitude of the tobacco problem in a dental school patient population
      and determine patients' interest and success in cessation. The study reviewed
      1,030 randomly selected charts of patients who were seen during 2004. Of these
      surveys, 1,025 met the study criteria: a medical history form with completed
      questions concerning tobacco usage. Of the 1,025 surveys reviewed, 565 patients
      (55%) had used tobacco and 219 (39%) continued to use tobacco products, including
      25 current users whose attempts to quit had failed. Surprisingly, 32% of the 219
      tobacco users were not interested in quitting. Patients in the 20-29 age group
      had the highest prevalence of current tobacco users. Tobacco cessation increased
      steadily with age; the cessation trend was 21% in patients aged 20-29, increasing
      steadily to 100% prevalence among patients 90 or older. Tobacco usage also was
      found to be more prevalent among men than among women. Of the total patient
      population, 25% were current smokers, a percentage well above the national health
      goal to reduce tobacco usage to 12% by 2010. Dental care providers must work to
      reduce the percentage of tobacco-using patients by providing cessation
      information and support.

PMID- 18050587
TI  - Knowledge, attitudes, practices, and training needs of Kentucky dentists
      regarding violence against women.
AB  - Dentists may be the first (and perhaps the only) health care professionals to
      treat patients who have experienced oral facial trauma resulting from domestic
      violence. Dentists are likely to see the signs of abuse while performing an oral
      examination and they often develop relationships with patients that could allow
      them to detect subtle changes in patients that may indicate signs of domestic
      violence. This study sought to assess the knowledge, attitudes, practices, and
      training needs of Kentucky dentists regarding domestic violence against women
      (VAW). A written survey was sent to a population of 1,892 eligible licensed
      dentists in Kentucky; 790 (42%) were returned. Ninety percent of the respondents
      were general dentists and the distribution by practice location was almost equal
      among urban, suburban, and rural dentists. Only 7.0% of respondents reported
      having any training in the prevention of VAW. When asked "... are you legally
      required to report suspected cases of VAW to the appropriate authorities,
      regardless of the patient's wishes?", 42% answered "no." An overwhelming majority
      (82%) indicated that they would like more training and information regarding VAW
      identification and management. Based on analysis of the data, Kentucky dentists
      would benefit from and be interested in additional education opportunities
      concerning recognizing, referring, and managing patients who may be the victim of
      domestic violence.

PMID- 18050588
TI  - Oral diagnosis. Mandibular radiopacities. Idiopathic osteosclerosis.

PMID- 18050589
TI  - Oral diagnosis. Panoramic radiopacities. Sialolithiasis.

PMID- 18050590
TI  - [Unexpected diagnosis in a child. Herpes zoster].

PMID- 18050591
TI  - [Preventing the spontaneous fracture in your patients].

PMID- 18050592
TI  - [Vertebral body fracture--or what?].

PMID- 18050593
TI  - [Elderly patients with gastrointestinal symptoms--what you must keep in mind].

PMID- 18050594
TI  - [Special gastrointestinal problems of elderly patients].
AB  - Only a few gastrointestinal diseases develop specifically at advanced ages (e.g.
      Zenker diverticulum, atrophic gastritis, mesenterial ischaemia). However, the
      frequency of certain diseases increases and various illnesses are found to take
      other, mostly silent, courses in elderly people. As a rule, more complications in
      gastrointestinal diseases are to be expected and the presence of comorbidities
      can make diagnosis and therapy more difficult. The possibility of tumours should
      always be considered in the differential diagnosis of elderly patients. The
      diagnosis and treatment of elderly patients for gastrointestinal diseases are no
      different from that of other age groups.

PMID- 18050595
TI  - [Drug side effects as the cause of gastrointestinal problems in elderly people].
AB  - Adverse drug reactions on the digestive tract are very common. Some special
      aspects must be heeded, especially in geriatric patients who often take several
      medications concomitantly. These include a potentially altered drug metabolism,
      possible lack of compliance, potential drug interactions as a result of
      polypharmaceutical therapy, the influence of comorbidities as well as the
      possibility of increased sensitivity and hence, toxic effect on the target
      organs.

PMID- 18050596
TI  - [Scurvy--a wrongly forgotten avitaminosis].
AB  - We treated a chronic alcoholic patient who showed all the symptoms of scurvy
      (petechiae, greyish skin colour, areas of thinning hair on the head, gingivitis,
      elevated liver enzyme levels, hyponatraemia, hypalbuminaemia and hypothyroidism)
      at admission. Even today, alcoholics and chronically ill people in particular can
      develop symptoms of diet-related vitamin C deficiency.

PMID- 18050597
TI  - [Relaxation techniques for patients with high blood pressure].

PMID- 18050598
TI  - [How do you clarify acute lumbago?].

PMID- 18050599
TI  - [How to manage patients who complain].

PMID- 18050600
TI  - [Epidemiology of over- and underweight in Swiss college students].
AB  - Overweight and obesity rates are increasing worldwide. In this study 409
      adolescents and young adults (age range 15-22 years) in a Swiss college were
      studied. The prevalence of overweight was 6.13% in the girls and 5.95% in the
      boys. 9.52% of the boys and 16.51% of the girls were underweight (BMI < 18.5
      kg/m2). 16.98% of the girls had a fat mass > 30%. 2.98% of the boys had a fat
      mass of > 20%. Male adolescents with a fat mass > 15% judged their physical
      activity on a visual analogue scale (VAS) significantly lower than male
      adolescents with a fat mass of < 15% (mean +/- SD VAS score: 4.49 +/- 2.08 vs.
      6.00 +/- 2.08, p = 0.03). The same was found in female adolescents: girls with a
      fat mass > 30% reported a lower physical activity level than females with a fat
      mass < 30% (mean +/- SD VAS score: 4.84 +/- 1.74 vs. 5.68 +/- 1.82, p = 0.04).
      Obesity and fatness, but also underweight, is a serious problem in Swiss
      adolescents. Well chosen public health strategies to address both sides of the
      energy balance equation are strongly needed.

PMID- 18050601
TI  - [Adrenal insufficiency and hypercalcemia--an unusual presentation].
AB  - A 49 y.o. man was admitted for investigation of an intense fatigue associated
      with nausea, vomiting, weight loss and headache. Examination and work-up reveals
      a moderate hypercalcaemia and a panhypopituitarism attributed to a
      craniopharyngioma. Extensive work-up has excluded the most frequent causes of
      hypercalcaemia and we finally attributed this anomaly to the adrenal failure. In
      this article, we discuss the diagnostic approach, the etiology and
      physiopathology of this hypercalcemia and his association with endocrinological
      anomalies such as adrenal failure.

PMID- 18050602
TI  - [Really drunk?].
AB  - We report about a 42-year-old patient who was admitted to the emergency
      department because of suspected alcohol abuse. He declared himself to be drunk.
      He stated in his case history that he had suffered from right sided neck and
      facial pain for several days. The clinical examination revealed a left sided
      hemiparesis. Together with the demonstrated right hemispherical brain ischemia by
      computed tomography, a presumptive diagnosis of a dissection of the right
      internal carotid artery was made. This diagnosis was finally confirmed by
      ultrasound and magnetic resonance imaging. A therapy with full dose heparin was
      begun and oral anticoagulation was subsequently initiated. After two weeks of
      follow-up, the neurological deficiencies were partially regredient.

PMID- 18050603
TI  - [Chronic fatigue. IV--Assessment of a 40-year-old patient].
AB  - A forty year old patient was referred by the federal insurance for medical
      assessment. His presenting complaint was chronic fatigue. The patient had been an
      intravenous drug user for years and had been infected with hepatitis C. He was
      treated with interferon. The patient history showed that he also suffered from
      anaemia and depression. He participated in a methadone substitution program. Our
      diagnostic procedures showed that he also has Hashimoto's thyroiditis.

PMID- 18050604
TI  - [CME--laboratory 4. "Tumor marker"].

PMID- 18050605
TI  - [How laboratories came to the Amazon or the ethnopathology of Max Kuczynski].

PMID- 18050606
TI  - [Contraception--methods of preventing pregnancy. Part I: fertility,
      contraception, natural methods of birth control].
AB  - The right to have a desired number of children is one of the main human rights
      Physical contacts, which are the source of considerable satisfaction and
      pleasure, are often performed not only for procreation. Human fertility depends
      mainly on the age, and is the highest in young women. Therefore, the group of
      patients who are emotionally immature but biologically mature enough to become
      mothers, needs the most effective prevention methods. There exist numerous
      methods of fertility control, which serve this purpose. In this article different
      contraception methods are presented. The natural methods, which consist in
      periodical sexual abstinence, are described in details. Their use can decrease
      the possibility of an unwanted pregnancy on hand, and facilitate the conceiving
      on the other.

PMID- 18050607
TI  - [Analysis of blood coagulation factors in patients undergoing surgery due to
      endometrial cysts].
AB  - OBJECTIVES: The study was undertaken to evaluate selected blood coagulation
      factors in patients undergoing surgery, due to endometrial cysts and other
      ovarian benign cysts. MATERIALS AND METHODS: Women involved in our study had not
      received any previous treatment for endometriosis and they had no history of any
      prior haemostatic disorders. Blood samples were collected before surgery and
      investigated for plasminogen, alpha2-antyplasmin, PAI-1 and tPA activity. As a
      control group, we have analyzed patients with benign gynecological diseases
      treated in our Department. RESULTS: We have noticed higher mean concentration of
      plasminogen and alpha2-antyplasmin and lower mean concentration of PAI-1 and tPA
      activity in our patients in comparison with control group. Obtained results did
      not show any statistical significance. CONCLUSIONS: Our analysis of haemostatic
      factors in blood samples did not show coagulation disorders in patients with
      endometriosis. Maybe there are only local coagulation disorders in endometrial
      tissue and its surrounding. In our opinion this problem requires further research
      and taking into consideration other factors.

PMID- 18050608
TI  - [The analysis of CFTR mutations in men with azoospermia, oligozoospermia and
      asthenozoospermia].
AB  - Mutations in cystic fibrosis transductance regulator gene (CFTR) are known to
      result in some forms of male infertility. An association between CFTR gene
      mutations and obstructive azoospermia in cystic fibrosis (CF) and in congenital
      unilateral and bilateral absence of vas deferens (CUAVD, CBAVD) has been proven.
      However, the role of CFTR gene mutations in the etiology of non-obstructive
      azoospermia, as well as in the regulation of spermatogenesis remains unsolved.
      OBJECTIVES: The aim of the study was to evaluate the frequency of CFTR mutations
      in patients diagnosed with different forms of spermatogenesis impairment
      MATERIAL: The molecular analyses were performed in the group of 93 infertile men,
      diagnosed with either azoospermia, oligospermia or asthenoteratozoospermia.
      RESULTS: The results of the study revealed the presence of F508del and IVS8-T in
      5.4% of analyzed cases. No difference in CFTR gene mutations frequencies among
      patients with azoospermia, oligospermia and asthenoteratozoospermia has been
      observed. CONCLUSION: The CFTR gene mutations frequency in men with
      nonobstructive azoospermia, oligozoospermia and asthenozoospermia is similar to
      those observed in general population.

PMID- 18050609
TI  - [Co-occurence of indol-producing bacterial strains in the vagina of women
      infected with Chlamydia trachomatis].
AB  - OBJECTIVES: The aim of this study was to determine if cervicitis, caused by
      Chlamydia trachomatis (C. trachomatis), has an influence on the frequency of
      occurrence of selected aerobic and anaerobic bacterial strains, connected with
      etiology of aerobic vaginitis (AV) and bacterial vaginosis (BV). Indole-producing
      bacteria have received particular attention due to their possibly inductive role
      in chronic cervicitis caused by C. trachomatis. MATERIAL AND METHODS: The swabs
      from vagina and cervical canal have been obtained from 122 women (aged 18-40).
      The presence of C. trachomatis antigen had been detected and diagnosed with the
      help of direct immunofluorescence, BV with Amesl and Nugent criteria, whereas the
      AV with Donders criteria. The identification of the bacterial strains isolated
      from vagina has been performed according to classical microbiological
      diagnostics. RESULTS: Disruption of vaginal microflora (4-10 in Nugent score) was
      determined in 11,5% of observed women. AV was diagnosed in 4.5% women with
      chlamydial cervicitis, BV was diagnosed in 10.9% and 5.45% of these women, on the
      basis of Amsel and Nugent criteria respectively. CONCLUSIONS: Indole-producing
      bacterial strains connected with BV and AV (Peptostreptococcus anaerobius,
      Propionibacterium acnes, Escherichia coli) have been isolated significantly more
      often from vagina of women infected with C trachomatis (p = 0.0405, chi2 = 4.20)
      and these findings confirm co-importance of indole-producing bacterial strains in
      cervicitis caused by C trachomatis .

PMID- 18050610
TI  - [Nasal bone (NB) length measurement in the first trimester of pregnancy in Polish
      population and its validity as fetal aneuploidy indicator].
AB  - OBJECTIVES: Dynamic development of prenatal diagnostics is mostly directed
      towards search for non-invasive screening. The main role of the screening methods
      is to select high-risk fetal aneuploidy group of pregnant women. The base for the
      prenatal screening in modern obstetrics is ultrasound scanning. DESIGN: The aim
      of the study was to estimate typical value range for the fetal nasal bone length
      measurement (NB) between 11th and 20th week of pregnancy, in Polish population.
      The second aim was to assess the value of the parameter as an aneuploidy marker.
      MATERIALS AND METHODS: The study was conducted between 1999-2006, in the 1st
      Division of Obstetrics and Gynaecology, Medical University in lodz. The
      investigated population comprised 2960 pregnant women. 53 cases of the fetal
      chromosomal aneuploidies were diagnosed. RESULTS: Typical values for the nasal
      bone measurement were estimated. The investigations showed that until 13th
      gestation week, visualization of the presence or absence of the nasal bone on the
      ultrasound scan is a better marker for fetal aneuploidy diagnosis than the
      measurement. However, since the 14th week, it is the measurement that becomes the
      most adequate method of the fetal nasal bone assessment. CONCLUSIONS: (1) We
      estimated the normal value range for the fetal nasal bone length measurement (NB)
      between 11 and 20 weeks of pregnancy. (2) The nasal bone length is an useful
      marker for the fetal aneuploidy. 3. The predictive value of the method suggests
      the visualization of the nasal bone presence in the 1st trimester of the
      pregnancy as a screening method. The measurement of the NB proves to be a useful
      method in the prenatal diagnostic in the 2nd trimester of the pregnancy.

PMID- 18050611
TI  - [Fetal activin A in labor complicated by meconium-stained amniotic fluid].
AB  - OBJECTIVE: During pregnancy the placenta and the fetal membranes are the main
      sources of activin A. An increased level of activin A has been found in the serum
      of women with preeclampsia, diabetes mellitus and intrauterine growth
      restriction. Meconium is the predictor for adverse perinatal outcome, such as
      meconium aspiration syndrome or brain damage. The aim of our study was to
      evaluate the levels of fetal activin A in labors complicated by meconium-stained
      amniotic fluid. MATERIAL AND METHODS: Cord blood samples were collected from 65
      full-term neonates from single pregnancies. In each case, the hematological
      parameters of cord blood and activin A (ELISA--Oxford Bio-Innovation Activin A
      Assay Kit) were assessed. RESULTS: There were no significant differences in the
      concentration of activin A in cord blood between the group with and the group
      without meconium-stained amniotic fluid. The mean count of nucleated erythrocytes
      and white blood cells as well as the percentage of reticulocytes was
      significantly higher in the meconium group. There were no significant differences
      between concentration of fetal activin A in a vaginal delivery (0.58 +/- 0.38
      ng/ml) and cesarean section after labor (0.44 +/- 0.32 ng/ml) or elective
      cesarean section (0.62 +/- 0.47 ng/ml) groups. There were also no correlations
      between the levels of activin A and the parameters of fetal acid base status or
      cord blood hematological values. CONCLUSIONS: Fetal activin A has a limited
      significance for diagnosing fetal hypoxia in labors complicated by meconium
      stained amniotic fluid. There were no correlations between the parameters of
      fetal acid base status and fetal activin A. The levels of fetal activin A do not
      depend on the mode of the delivery. Meconium-stained amniotic fluid resulted in
      significant changes of the hematological variables in cord blood.

PMID- 18050612
TI  - [Search for the etiopathogenesis of polycystic ovary syndrome (PCOS)].
AB  - Polycystic ovary syndrome (PCOS) is a common disorder which affects about 10% of
      women in reproductive age. According to the Rotterdam consensus criteria, PCOS is
      diagnosed in the presence of two out of three following symptoms: (1)
      oligomenorrhoea, anovulation, (2) hyperandrogenism, (3) polycystic ovaries at
      ultrasound scan. Etiology of the syndrome, although widely speculated, still
      remains unknown. Analysis of the prevalence of PCOS among the families reveals
      that genetic contribution to the outcome of the syndrome is highly probable.
      However, the pattern of inheritance is not clear. On the basis of common clinical
      symptoms, disorders in metabolic pathways involved in biosynthesis and action of
      steroid hormones and insulin, as well as in development of inflammatory state,
      have been searched. As part of the research, large-scale analysis of "candidate
      genes", whose protein products are engaged in several metabolic processes, have
      been performed. According to research, at least in some of them mutations or
      polymorphisms, mainly SNP-type, affecting transcription of the gene or protein
      properties, have been found. Nevertheless, none of them seem to play a key role
      in the pathogenesis of the syndrome, indicating that PCOS may be a result of
      several genes abnormalities interactions. In this review we present the current
      state of knowledge concerning particular genes, products of which seem to take
      part in the modulation of the clinical sings of the disease.

PMID- 18050613
TI  - [Xenobiotics influence on estrogen activity].
AB  - Many chemical compounds which imitate estrogens effect are present in the
      environment. There are natural substances (phytoestrogens), as well as synthetic
      (xenoestrogens, metaloestrogens) ones. A lot of xenobiotics are inductors or
      inhibitors of enzymes, also those enzymes which take part in estrogens
      metabolism. However, little is still known about the influence of xenobiotics on
      estrogens activity, there can be no question of the importance of the problem.
      One of them are the diminished effects of endogenous estrogens in women smokers,
      also weakness or lack of oral hormonal replacement therapy (HRT) effect among
      women smokers, as well as the influence of estrogens on dioxins toxicity. The
      issue of estrogen compounds presence in cosmetics deserves special attention. It
      is essential for us to remember, that estrogens are compounds with high
      biological activity. Thus, hormonal balance disturbance can have serious health
      consequences, including tumors. In this research we have attempted to present a
      review of studies which concern exogenous factors influence on estrogens activity
      and have summarized current state of knowledge.

PMID- 18050614
TI  - [Combined oral contraception and the risk of reproductive organs cancer in
      women].
AB  - COCs (combined oral contraceptives) remain the most widely used effective and
      reversible means of family planning. Their beneficial effects are well
      documented, but many questions are still raised concerning a possible association
      between the use of COCs and the development of cancer. The authors provide a
      broad and up-to-date review of the literature regarding the relation between COC
      use and carcinogenesis in reproductive organs. Studies have not unequivocally
      confirmed that such a relation exists with regard to breast cancer. Much research
      has been focused on the COCs usage and its positive connection with the incidence
      of cervical cancer; most of it was done by J. Smith. This author confirmed the
      existence of a weak relation between COCs and the development of cervical
      carcinoma, especially in women using COCs for longer periods. Ovarian carcinoma
      has the worst prognosis of all cancers of reproductive organs in women.
      Nonetheless, the risk of developing ovarian cancer in women using COCs is at
      least 40% smaller than in other women; the degree of protection given by COCs
      being proportional to the duration of use of this form of contraception.
      Scientific data proved convincingly that the risk of endometrial cancer is
      smaller in COCs users than in women who never took COCs.

PMID- 18050615
TI  - [Leptin, leptin gene, leptin gene receptor polymorphisms and pregnancy].
AB  - The article presents information about leptin as the major metabolic hormone. The
      structure, localization of the hormone and its receptor have been described
      focusing on maturation and fertility processes. Several polymorphisms of leptin
      gene and its receptor have been described as potential developmental factors of
      pregnancy complications such as diabetes mellitus or pregnancy induced
      hypertension.

PMID- 18050616
TI  - [Perinatal results of intrauterine open fetal surgery of fetuses diagnosed with
      myelomeningocoele--the clinical report of ten cases].
AB  - The purpose of the study was to demonstrate our approach to qualification for
      open fetal surgery (OFS) and surgery techniques. We also tried to determinate the
      outcome of fetal surgical treatment. OFS was performed in 10 out of 15 cases with
      prenataly diagnosed myelomeningocele. Patients were qualified for the surgery on
      the basis of precisely determined inclusion criteria and after assessment by
      multidisciplinary team of specialists. Surgery was performed between 22nd and
      29th week of pregnancy. Fist and second surgery were performed in 29th and 27th
      week of pregnancy, some patients have undergone the surgery before 26th week of
      pregnancy. Babies were delivered by cesarean section. Gestational age by the time
      of the delivery ranged from 25th and 37th and a half week of pregnancy. In two
      cases the delivery was at term. Main complications included: PROM, placental
      ablation and vaginal bleeding. In half of all the cases we did not observe
      hydrocephalus increase after the surgery. OFS can be beneficial but it can also
      carry certain amount of risk both for the fetus and the mother. Therefore,
      further randomized research deems necessary to better comprehend and determine
      the safety and effectiveness of such procedures.

PMID- 18050617
TI  - [CTG--sinusoidal tracing].

PMID- 18050618
TI  - [Influence of acupuncture on the immune function of immunosuppressive Cx43
      knockout mice].
AB  - OBJECTIVE: To observe the influence of acupuncture on the immune function in
      immunosuppressive Cx43 knockout mice so as to explore the relationship between
      connexin 43 (Cx43) and acupuncture signal transmission. METHODS: Eighteen male
      Cx43 knockout mice (Cx43 + / -, 8-9 weeks old) and eighteen wide-type mice (Cx43
      + / + ) were divided into normal group, model group and acupuncture group
      randomly, with 6 cases in each. The immunosuppressive mice model was established
      by intraperitoneal injection of Cyclophosphamide. Mice in acupuncture group were
      treated with manual acupuncture of "Zusanli" (ST 36) and "Guanyuan" (CV 4), once
      daily for 7 days. Spleen index, thymus index, number of leukocytes in the
      peripheral blood were calculated and the percentage of T lymphocyte subpopulation
      was detected by using flow cytometry. RESULTS: Compared with normal control
      group, the spleen index, thymus index and leukocyte number of model group in both
      Cx43 + / + mice and Cx43 + / - mice were obviously lower (P < 0.05, 0.01), while
      in Cx43 + / + mice and in comparison with model group, the spleen index, thymus
      index and leukocyte number of acupuncture group were significantly higher (P <
      0.05, 0.01) and no significant differences were found between acupuncture group
      and control group (P > 0.05). But in Cx43 + / - mice , no obvious differences
      were found between acupuncture and model groups in the aforementioned 3 indexes
      (P > 0.05), showing a disappearance of the effect of acupuncture in raising
      immune function after Cx43 knockout. There were no obvious differences between
      two control groups and between two model groups in the 3 indexes of Cx43 + / +
      mice and Cx43 + / - mice. The immune function of Cx43 + / + mice was obviously
      stronger than that of Cx43 + / - mice in acupuncture group. CONCLUSION: Knockout
      of Cx43 gene inhibits the effect of acupuncture in reinforcing mouse immunity,
      suggesting an important role of Cx43 in the transmission of acupuncture signals
      for adjusting immunity function.

PMID- 18050619
TI  - [Effect of electroacupuncture of "Neiguan" (PC 6) on Na+-K+-ATPase activity and
      its gene expression in cardiocyte membrane in rats with myocardial ischemia
      reperfusion injury].
AB  - OBJECTIVE: To compare the effects of electroacupuncture (EA) of "Neiguan" and
      other acupoints on Na+ -K+ -ATPase activity and its gene expression in ischemic
      myocrardial cell membrane in rats. METHODS: A total of 50 Wistar rats were
      randomly divided into pseudo-operation (control), model, Neiguan (PC6), Shenmen
      (HT7) and Hegu (LI4) groups, with 10 rats in each group. Myocardial ischemia
      reperfusion (I/R) model was duplicated by occlusion of the descending anterior
      branch of the left coronary artery and reperfusion. EA (30/100 Hz, 2-4 mA) was
      applied to the above-mentioned acupoints for 20 min respectively. Na+ -K+ -ATPase
      activity was determined by inorganic phosphorus colorimetry, and Na+ -K+ -ATPase
      gene expression was detected using reverse transcription polymerase chain
      reaction (RT-PCR) technique. RESULTS: Compared with control group, the activity
      of Na+ -K+ -ATPase in model, PC6, HT7 and LI4 groups decreased significantly
      after myocardial I/R (P<0.05, 0.01); while in comparison with model, the activity
      of Na+ -K+ -ATPase in PC6 group increased considerably (P<0.01). Regarding the
      expression of Na+ -K+ -ATPase mRNA, compared with control group, it was down
      regulated significantly in model, HT7 and LI4 groups (P<0.01); while in PC6
      group, Na+ -K+ -ATPase mRNA expression was up-regulated markedly compared with
      model group (P<0.05); The activity of Na+ -K+ -ATPase and the expression of Na+ 
      K+ -ATPase mRNA in HT7 and LI4 groups were significantly lower than those in PC6
      group (P<0.01, 0.05). No significant differences were found between HT7 and LI4
      groups in the activity of Na+ -K+ -ATPase and the expression of Na+ -K+ -ATPase
      mRNA (P>0.05). CONCLUSION: EA of "Neiguan" (PC6) may potentiate the activity of
      Na+ -K+ -ATPase and up-regulate Na+ -K+ -ATPase mRNA expression, which may
      contribute to its protective effect on ischemic cardiocytes.

PMID- 18050620
TI  - [Effects of acupoint-embedding of medicinal thread and electroacupuncture on
      contents of TNF-alpha and IL-6 of hippocampus tissue in rats with focal cerebral
      ischemia-reperfusion injury].
AB  - OBJECTIVE: To observe the effects of acupoint-embedding (AE) of collagen plus
      Tetramethylpyrazine and electroacupuncture (EA) on the contents of TNF-alpha and
      IL-6 in hippocampus tissue in rats with focal cerebral ischemia-reperfusion (CI
      R) injury. METHODS: A total of 120 SD rats were randomly divided into normal
      control (n=8), sham operation (n=24), model (CI-R, n=24), EA (n=24) and AE (n=24)
      groups, and the later 4 groups were further divided into 24 h, 72 h and 120 h
      subgroups (time-points) separately, with 8 cases in each. CI-R model was
      established by middle cerebral artery occlusion (MCAO) and reperfusion. For
      animals of AE group, the medicinal thread consisting of collagen and
      Tetramethylpyrazine was implanted into "Dazhui" (GV14) and bilateral "Neiguan"
      (PC6), once daily. For rats of EA group, EA (120 cycles/min, 1 mA) was applied to
      GV14 and PC6 for 30 min, once daily. The contents of TNF-alpha and IL-6 in the
      hippocampus were detected by using radio-immunoassay after processing the tissue
      samples (homogenate, centrifuge). RESULTS: The contents of TNF-alpha and IL-6 in
      hippocampus tissue of model group at 24 h, 72 h and 120 h time-points were
      significantly higher than those of normal control and sham operation groups
      (P<0.05), while after EA and AE, the contents of TNF-alpha at the 3 time-points
      decreased significantly (P<0.05), and IL-6 contents at the same 3 time-points
      increased further and significantly (P<0.05). Comparison between EA and AE groups
      showed that the contents of TNF-alpha of the later group at 72 h and 120 h were
      significantly lower than those of EA group (P<0.05), while IL-6 contents of AE
      group were significantly higher than those of EA group at the same time-points
      (P<0.05). CONCLUSION: Both EA and AE of collagen and Tetramethylpyrazine can
      evidently lower TNF-alpha content and significantly raise IL-6 level in
      hippocampus in rats with cerebral ischemia/reperfusion injury and the effect of
      AE is significantly superior to that of EA, which may contribute to their
      protective effects on ischemic cerebral neurons.

PMID- 18050621
TI  - [Observation on the analgesic effect of repeated electroacupuncture and its
      relation to changes of plasma beta-EP, ACTH and COR levels].
AB  - OBJECTIVE: To observe the regularity of electroacupuncture (EA) analgesia and to
      analyze its relation to hypothalamus-pituitary-adrenal cortex axis function in
      chronic constrictive injury (CCI) and ovariectomy (OVX) rats. METHODS: A total of
      110 Wistar rats anesthetized with mixture solution of 1.5% chloralose (50 mg/kg)
      and 25% urethrane (420 mg/kg, i.p.) were randomized into control (n=10), CCI (n
      =10), CCI + EA (n=30), OVX + CCI (n=30), OVX + CCI + EA (n=30) groups, and the
      later 3 groups were further divided into 2 times (2 t), 2 weeks (2 w) and 3 w
      time courses, with 10 cases in each. Forty-five days after OVX, Morris water maze
      test was conducted to evaluate the OVX rats' memory-learning ability. Chronic
      pain model was established by ligating the right sciatic nerve with a piece of
      suture. EA (2/15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST 36)
      "Yanglingquan" (GB 34) for 30 min, once daily for 2 t, 2 w, 3 w respectively. The
      paw withdrawal latency (PWL) was detected to be used as the pain threshold. Under
      deep anesthesia, the rat was decapitated for collecting blood samples. Plasma
      adrenocorticotropic hormone (ACTH), beta-endorphine (EP), cortisone (COR)
      contents were detected using radioimmunoassay. RESULTS: In comparison with
      control group, PWL difference values (PWLDV) of CCI + EA, OVX + CCI and OVX + CCI
      + EA groups increased significantly (P<0.05), suggesting a marked decrease of
      pain threshold. Compared with CCI group, PWLDV of CCI + EA group at 3 w decreased
      significantly (P<0.05), being close to normal control group (P>0.05). Compared
      with OVX + CCI group, PWLDV of OVX + CCI + EA at 2 w and 3 w lowered
      significantly (P<0.05), suggesting an evident pain relief. In comparison with CCI
      + EA group, PWLDV of OVX + CCI + EA group at most time courses were considerably
      higher (P<0.05), showing a better cumulative analgesic effect in CCI rats without
      OVX. In CCI group, plasma beta-EP increased slightly, ACTH had no clear changes,
      and COR lowered lightly at 2 t. No significant differences were found between
      control and CCI + EA groups in beta-EP and ACTH levels at 2 w and 3 w (P>0.05),
      only COR levels of CCI + EA group at 2 w and 3 w increased significantly
      (P<0.05). Compared with control group, beta-EP levels of OVX + CCI group at 2 w
      and 3 w increased significantly (P<0.05); plasma ACTH had no marked changes
      (P>0.05); COR contents of OVX + CCI group decreased evidently at 2 t and
      increased markedly at 2 w (P<0.05). Compared with OVX + CCI group, in OVX + CCI +
      EA group, beta-EP levels of 2 t and 2 w decreased significantly (P<0.05); ACTH
      levels increased evidently at 2 t and 3 w, and decreased markedly at 2 w
      (P<0.05); and COR level at 2 w decreased significantly (P<0.05). It indicated
      that when cumulative EA analgesia appeared, in CCI animals, only plasma COR level
      increased pronouncedly, while in OVX + CCI rats, both plasma beta-EP and COR
      contents decreased evidently. CONCLUSION: Both plasma beta-EP and COR are
      involved in the accumulative analgesic effect of EA in the rat, and decline of
      learning memory ability may weaken the analgesic effect of EA to a certain
      degree, but no clear correlation tendency is found between changes of plasma beta
      EP and COR and the improvement of pain behavior.

PMID- 18050622
TI  - [Effect of acupuncture of different acupoints on electrical activities of
      hypothalamic sexual arousal stimulation-related neurons at different stages of
      oestrous cycle in rats].
AB  - OBJECTIVE: To compare the effects of acupuncture stimulation of different
      acupoints on discharges of hypothalamic sexual arousal stimulation-related
      excitatory neurons in the rat so as to selected effective acupoints for
      regulating genito-endocrine function. METHODS: Experiments were performed in 32
      female Sprague-Dawley rats. Examination of vaginal castoff cell smear (HE
      staining) was performed to determine the rats' estrous cycle. Those being in
      proestrus/estrus were 14 animals and those being in diestrus/metaestrus were 18.
      Extracellular discharges of neurons within the medial preoptic area, the arcuate
      nucleus and the paraventricular nucleus of the hypothalamus (AP: 4.0-9.0 mm, R:
      <1.0 mm, L: <2.0 mm) were recorded by using glass micro-pipettes in anesthetized
      rats (10% urethane). Sexual arousal stimulation was made by using a cotton-ball
      stick to touch the clitoris repeatedly (30 s). When a marked change of the
      neuronal firing rate was found, beta-estradiol (20 ng/mL, 1.5-2.5 mL/kg) was
      injected intravenously from the external jugular vein for observing its feedback
      regulatory effect. Acupoints "Neiguan" (PC6), "Shanzhong" (CV17), "Jueyinshu"
      (BL14), "Zhongwan" (CV12), Shenshu" (BL23), "Guanyuan" (CV4), Z"igong" (EX-CA )
      and "Zusanli" (ST 6) were punctured and stimulated manually by twirling the
      acupuncture needle continuously for 30 s. RRESULTS After manual acupuncture, the
      sequence of acupoints with a stronger excitatory reaction of the firing rates of
      the hypothalamic neurons related to sexual arousal stimulation was EX-CA1, CV4,
      ST36, BL23, CV12, BL14, PC6 and CV17 in proestrus/estrus; and CV4, EX-CA1, ST36,
      CV12, BL23, BL14, PC6 and CV17 respectively in diestrus/metaestrus. According to
      the place of the stimulated acupoints potentiating the electrical activity of the
      hypothalamic sexual arousal stimulation-related neurons, the sequence from
      stronger to the weaker responses was lower abdomen (below umbilicus), lower limb,
      lower back (L1-S5), upper abdomen, upper back (above T12), thorax, and upper
      limbs. After administration of estradiol, the excitatory response of these sexual
      arousal-related neurons decreased significantly in both estrus and non-estrus
      (P<0.05). CONCLUSION: Acupuncture can effectively activate the electrical
      activity of hypothalamic sexual arousal stimulation-related excitatory neurons.
      The closer the acupoint to the genital organs, the stronger is the excitatory
      effect, including "Zigong" (EX-CA1), "Guanyuan" (CV4) and "Zusanli" (ST36) among
      the 8 acupoints observed.

PMID- 18050623
TI  - [Effects of pricking bleeding at "Weizhong" (BL40) on sciatic nerve conduction
      velocity and interleukin-1alpha content in the lumbar vertebral nucleus pulposus
      in experimental lumbar intervertebral disc protrusion rabbits].
AB  - OBJECTIVE: To observe the effect of "Weizhong" (BL40) bleeding on sciatic nerve
      conduction velocity (SNCV) and interleukin-1alpha (IL-1alpha) content of the
      lumbar vertebral nucleus pulposus tissue in experimental lumbar intervertebral
      disc protrusion (LIDP) rabbits so as to explore the underlying mechanism of blood
      letting in the treatment of LIDP. METHODS: Forty healthy New Zealand rabbits were
      randomly assigned to control, model, BL40 and non-point (1 cm medial to BL40)
      groups, with 10 cases in each group. LIDP model was established by pushing the
      intervertebral disc tissue rightward to protrude the posterior longitudinal
      ligament with a self-made instrument after exposing the L6-7 vertebrae and
      intervertebral space. Blood-letting was performed at "Weizhong" (BL40) and non
      point by using a triangle-edged needle to prick the local tissue, once daily and
      continuously for 7 days. SNCV was detected by using BL-410 physiological signal
      recording system, and the content of IL-1alpha in L6-7 intervertebral disc tissue
      determined with enzyme linked immunsorbent assay (ELISA). RESULTS: In comparison
      with control group and pre-modeling, SNCV decreased significantly in model, BL40
      and non-acupoint groups after LIDP; while compared with model group, values of
      SNCV in BL40 group increased considerably (P<0.05), no significant changes were
      found between non-acupoint group and model group (P>0.05). Compared with control
      group, the contents of IL-1alpha in the nucleus pulposus in model and non
      acupoint groups increased remarkably (P<0.05, 0.01), but no significant
      difference was found between control and BL40 groups in IL-1alpha level (P>0.05).
      CONCLUSION: Blood-letting at "Weizhong" (BL40) can relieve LIDP-induced nerve
      injury and mechanical oppression to improve SNCV, which may be closely related to
      its effect in decreasing inflammatory factor IL-1alpha level.

PMID- 18050624
TI  - [Effect of lysis of acupotomology on plasma vasoactive substance levels in rats
      with third lumbar vertebra transverse process syndrome].
AB  - OBJECTIVE: To observe the effect of small needle-knife lysis on plasma calcitonin
      gene-related peptide (CGRP), endothelin (ET), 6-keto-prostaglandin F1alpha (6
      keto-PGF1alpha), thromboxane A2 (TXA2) contents in rats with experimental third
      lumbar vertebra transverse process syndrome (TLVTPS) so as to explore its
      underlying mechanism in clinical treatment. METHODS: Forty SD rats were randomly
      divided into normal control, model, lysis and EA groups. TLVTPS model was
      established by embedding a piece of gelatin sponge (0.5 cm x 0.5 cm) to the
      transverse process of the 3rd lumbar vertebra under anesthesia. EA (2/100 Hz, 1-2
      mA) was applied to left "Shenshu" (BL23) -"Yaoyangguan" (GV3) for 20 min, once
      every other day, 6 times altogether. For animals of lysis group, the lysis was
      performed by using a small needle-knife in the induration spot or cord-like
      region near the incision, once a week and twice altogether. Four weeks later
      after modeling, plasma CGRP, ET, 6-keto-PGF1alpha and TXA2 contents were detected
      by using radioimmunoassay and enzyme linked immunosorbent assay (ELISA). RESULTS:
      Compared with normal control group, plasma CGRP, ET, TXA2 and 6-keto-PGF1alpha
      increased significantly in model group (P<0.01); in comparison with model group,
      plasma CGRP, TXA2 and 6-keto-PGF1alpha in both EA and lysis groups decreased
      considerably (P<0.05, 0.01). No significant differences were found between EA and
      lysis groups in plasma CGRP, ET and 6-keto-PGF1alpha levels (P>0.05). CONCLUSION:
      Both EA and lysis of acupotomology have an adjusting effect on vasoactive
      substances (CGRP, TXA2 and 6-keto-PGF1alpha) levels in TLVTPS rats, which may
      contribute to their effects in improving local blood circulation and relieving
      soft tissue injury in the treatment of third lumbar vertebra transverse process
      syndrome.

PMID- 18050625
TI  - [Effect of electroacupuncture and moxibustion of "Dazhui" (GV14) on the number
      and distribution of degranulated mast cells in GV14 region].
AB  - OBJECTIVE: To compare the effects of electroacupuncture (EA) and moxibustion on
      the degranulated mast cell number and distribution in "Dazhui" (GV14) region of
      rats. METHODS: Fifteen Wistar rats were randomly divided into normal control, EA
      and moxibustion groups, with 5 cases in each group. "Dazhui" (GV14) was
      stimulated by EA (3/10 Hz, 2-4 V, 20 mm) or moxibustion (2 cones, 20 mm),
      thereafter, the tissues of GV14 region were sampled, quickly frozen, sectioned
      (20 microm) and stained with toluidine blue separately for observing the
      degranulated state of mast cells under microscope. RESULTS: The mast cells (MCs)
      distributed widely in GV14 region from the dermis, subcutaneous tissue to muscle
      layer. Compared with control group, MCs of moxibustion group were significantly
      fewer in the number (P<0.05), and those degranulated MCs in both EA and
      moxibustion groups were evidently more in the number (P<0.01), and the number and
      percentage of the degranulated MCs in moxibustion group were significantly more
      than those of EA group (P<0.05), suggesting that EA and moxibustion could promote
      the release of granules of mast cells in the stimulated acupoint region, and the
      effect of moxibustion is stronger. CONCLUSION: Both EA and moxibustion can
      promote the degranulation of MCs, and the effect of moxibustion is markedly
      stronger in potentiating the release of granules from MCs in GV14 in rats.

PMID- 18050626
TI  - [Changes of cutaneous temperature and the activity of Ca2+- and Mg2+ -ATPase in
      the tissues along the running course of meridians in rabbit].
AB  - OBJECTIVE: To study the interrelation between the change of temperature and Ca2+
      , Mg2+ -ATPase activity in the tissues along the running course of meridians in
      the rabbit. METHODS: Seven healthy mongrel rabbits were used in this study.
      Before and after moxibustion of "Zusanli" (ST36) and "Yinlingquan" (SP9), the
      cutaneous temperature along the Stomach Meridian and Spleen Meridian was detected
      with an infra-red thermography. The tissues showing higher temperature (including
      skin, subcutaneous tissue and muscle, 100 mg) and non-higher temperature (skin,
      subcutaneous tissue and muscle about 0.5 cm beside the higher temperature region,
      100 mg) after moxibustion were sampled respectively for detecting the activity of
      Ca2+- and Mg2+ -ATPase with enzymologic method. RESULTS: After moxibustion of
      "Zusanli" (ST36) and 'Yinlingquan" (SP9), the temperature of the skin along the
      Stomach Meridian and Spleen Meridian on the same side increased significantly
      (P<0.05, 0.01); correspondingly, the activity of Mg2+ -ATPase in the higher
      temperature regions (lateral side of the left thigh, and the medial side of the
      right hindlimb) increased moderately and significantly separately in comparison
      with the control regions (P<0.05). No marked changes were found in the activity
      of Ca2+ -ATPase in the same tissues of the higher temperature regions (P>0.05).
      CONCLUSION: In the tissues of higher temperature region after moxibustion of SP9,
      Mg2+ -ATPase activity increased evidently, that may contribute to the increase of
      temperature along the skin of the Spleen Meridian after moxibustion, while Ca2+ 
      ATPase may play a minor role therein.

PMID- 18050627
TI  - [Effect of acupuncture on hemorheology in patients with diabetic nephropathy].
AB  - OBJECTIVE: To explore the underlying mechanisms of acupuncture in treating
      diabetic nephropathy (DN) by observing the effect of acupuncture on blood
      rheology of DN. METHODS: A total of 54 cases of DN patients were randomly divided
      into control (n=24) and acupuncture group (n=30). Patients of control group were
      treated with diet-control, oral administration of Gliguidone (30-60 mg, t. i. d.)
      or subcutaneous injection of insulin, and those of acupuncture group treated with
      the same medication as those of control group and additional manual acupuncture
      stimulation of Ganshu (BL18), Pishu (BL20), Zusanli (ST 36), etc., once daily for
      30 days. Hemorheology was detected with LBY-N6A Automatic Hemorheological
      Analyser. The treatment duration in 2 groups was 30 days. RESULTS: After the
      treatment, of the 24 and 30 cases in control and acupuncture groups, 6 (25.0%)
      and 16 (53.3%) cases experienced remarkable improvement in their symptoms; 10
      (41.6%) and 12 (40.0%) had improvement, 8 (33.3%) and 2 (6.7%) failed, with the
      effective rates being 66.7% and 93.3% respectively. Self-comparison showed that
      after the treatment, no significant changes were found in lower shear rate (LSR)
      and higher shear rate (HSR) of whole blood viscosity, plasma viscosity (etap),
      hematocrit (HCT) and profibrin in control group; while LSR of whole blood
      viscosity, etap and profibrin in acupuncture group decreased significantly
      (P<0.05). The therapeutic effect of acupuncture group was significantly superior
      to that of control group in lowering LSR of whole blood viscosity and profibrin
      (P<0.05). CONCLUSION: Acupuncture can improve DN patients' clinical symptoms and
      blood rheology, and hence, has a certain effect in postponing the development of
      DN.

PMID- 18050628
TI  - [Effect of different acupuncture needle-retaining time on hemorheology in
      ischemic stroke patients].
AB  - OBJECTIVE: To observe the effect of different needle-retaining duration on
      hemorheology in ischemic stroke patients in order to explore its underlying
      mechanism in the treatment of ischemic stroke. METHODS: A total of 251 ischemic
      apoplexy patients were, according to their state (mild, moderate and severe) of
      disease, randomly divided into 20 min, 40 min and 60 min groups respectively.
      Acupoints Jianyu (LI15), Quchi (LI11), Waiguan (TE5), Hegu (LI4), Futu (ST32),
      Zusanli (ST 36), etc. were punctured and stimulated electrically with parameters
      of 2 Hz, 2-6 mA for 20 min, 40 min and 60 min separately, once daily for 10
      times. In addition, the patients were also treated with medicines for lowering
      intracranial pressure as manicol, etc. Higher shearing rate (HSR) and lower
      shearing rate (LSR) of whole blood viscosity (etab), plasma viscosity (etap),
      hematocrit (HCT) and profibrin were detected separately before and after the
      treatment. RESULTS: After acupuncture treatment, of the 83, 80 and 82 cases in 20
      min, 40 min and 60 min groups, 3 (3.61%), 4 (5.00%) and 9 (10.98%) were cured
      basically, 15 (18.07%), 17 (21.25%) and 21 (25.61%) experienced remarkable
      improvement in their symptoms and signs, 24 (28.92%), 33 (41.25%) and 40 (48.78%)
      had an improvement, 41 (49.40%), 26 (32.50%) and 12 (14.63%) failed in the
      treatment, with the markedly effective rates being 21.68% , 26.25% and 36.59% and
      the effective rates being 50.60%, 67.50% and 85.37% separately. The effective
      rate of 60 min group was significantly higher than those of 20 min and 40 min
      groups (P<0.01, 0.05). Self-comparison showed that HSR, LSR of etab, etap, HCT
      and profibrin levels decreased considerably in comparison with pre-treatment in
      each group (P<0.01). Difference values of HSR, LSR, etap, HCT and profibrin (pre
      treatment--those of post-treatment) in 60 min group were significantly higher
      than those of 20 min and 40 min groups (P<0.05, 0.01), and those of HSR, HCT and
      profibrin of 40 min group were markedly higher than those of 20 min group
      (P<0.01, 0.05). The therapeutic effect of 60 min group was the best. CONCLUSION:
      Acupuncture can effectively improve stroke patients' symptoms and signs, and
      lower various parameters of hemorheology.

PMID- 18050629
TI  - [Randomized controlled study on the analgesic effect of superficial needling plus
      electrostimulation of sanyinjiao (SP6) for primary dysmenorrhea].
AB  - OBJECTIVE: To evaluate the analgesic and therapeutic effects of electro
      superficial-acupuncture (ESA) of Sanyinjiao (SP6) for treating primary
      dysmenorrhea (PD). METHODS: A total of 171 patients were randomly divided into
      ESA (n=57), superficial acupuncture (SA) (n=57) and medication (n=57) groups. For
      patients in SA group, bilateral SP6 were punctured superficially with special
      single-use needles, and for those in ESA group, after puncturing, electric
      stimulation (60 Hz, 2-3 V) was applied to SP6 for 30 min. Patients of medication
      group were ordered to take Brufen sustained-release capsules (0.3 mg, b. i. d.,
      for 3 days), then, take it again from the 3rd day on before the onset of
      menstruation to the 2nd day after the onset. The cumulative score of clinical
      symptoms were evaluated before and after the treatment. RESULTS: Comparison among
      3 groups showed that the difference values of score (pre-treatment--post
      treatment) of both ESA and SA groups were significantly bigger than that of
      medication group (P<0.001). After the treatment from 1 min to 30 min, patients
      with complete relief of dysmenorrhea of ESA group were significantly more than
      those of SA group during the 1st menstrual cycle (P<0.05). Results of intention
      to-treat (ITT) analysis showed that of the three 57 cases in ESA, SA and
      medication groups, the cured cases were 40, 38 and 10, the markedly effective
      were 9, 10 and 27, the effective were 5, 4 and 7, and the failed were 3, 5 and
      13, with the total effective rates being 94.74%, 91.23% and 77.19% respectively.
      The effective rates of ESA and SA groups were significantly higher than that of
      medication group (P<0.01), and the results of per-protocol analysis (PP) were
      similar to those of ITT analysis. CONCLUSION: The analgesic effect of both ESA
      and SA at SP6 for PD patients is significantly better than that of oral
      administration of Brufen.

PMID- 18050630
TI  - [Research of integrated traditional Chinese and Western medicine on regularity of
      clinical acupuncture].
AB  - In the present article, the authors, in the light of their research in recent a
      decade of years, make an overall summary on the regularities of clinical
      acupuncture from the stimulated points, the superficial and deep layers, the
      literature basis and the innovation points. These basic regularities include
      symmetry or corresponding, segmental innervation, center or central axis,
      superiority of distal limbs, ending-stimulation accelerating analgesia, periphery
      stimulation accelerating easiness and smooth, local feed back, specific feed
      back, selection of the stimulated points, acupuncture of different layers, etc..
      They also discuss the possibility of integration of traditional Chinese and
      Western medicine from the view-points of neuroanatomy, neurophysiology and
      rehabilitation medicine. Systematic analysis on the regularities of clinical
      acupuncture makes the ancient meridian-collateral theory and abundant clinical
      experience summed up in definite concepts, simplifies the complicated theory
      system of acupuncture learning, and favors the communication about the
      terminology of Chinese medicine and Western medicine.

PMID- 18050631
TI  - [Review on clinical application of needling techniques in chapter Guan Zhen
      (Official Needling Techniques) of Ling Shu (Spiritual Pivot)].
AB  - In the present paper, more than 380 theses related with clinical application of
      "nine needling techniques", "twelve needling techniques" and "five needling
      techniques" recorded in chapter Guan Zhen (Official Needling Techniques) of Ling
      Shu (Spiritual Pivot) were found through retrieving the data in the internet in
      latest 10 years. Among the 130 theses about clinical application of "nine
      needling techniques", 108 involve the application of opposing needling. Of the
      180 theses about clinical application of "twelve needling techniques", 95 involve
      the application of triple needling. Out of the 60 theses on clinical application
      of "five needling techniques", 37 involve the application of Hegu needling (multi
      direction needling). To sum up, the above-mentioned needling techniques were
      mainly applied to the treatment of diseases of dermatology, surgery, pediatrics,
      traumatology, five sense organs, etc.. It indicates that these needling
      techniques are widely being used in clinical practice now. Therefore, researchers
      should lay the stress on the scientific methodology, rigorous research process,
      as well as objective analysis of the results so as to make an objective
      conclusion and improve the level of the research.

PMID- 18050632
TI  - [Survey on the relationship between pathological reactions of acupoints and
      Zangfu organs/meridians].
AB  - In this article, the authors make an analysis on the regularity of correlation
      between pathological reactions of acupoints and Zangfu organs/meridians, current
      clinical application and mechanism research, and summarize the relative
      specificity of the correlation between abnormal reactions of acupoints and states
      of Zangfu organs/meridians. In addition, the authors also point out some
      shortcomings in current researches on the above-mentioned aspects, for examples,
      only observation on the phenomenon without definite conclusion on the regularity
      of acupoint reactions, being restricted in the objective specificity, etc.. They
      stress that we should sum up a series of regularities for clinical application
      (early diagnosis), and conduct profound research on its underlying mechanism in
      the coming days.

PMID- 18050633
TI  - [Semen Semenovich Girgolav (1881-1957)].

PMID- 18050634
TI  - [Surgical treatment of patients with post-infarction aneurysm of the left
      ventricle and diffuse lesion of the anterior interventricular artery].
AB  - Diffuse lesions of the anterior interventricular artery (AIVA) at different
      levels were diagnosed in 27 out of 417 patients operated for post-infarction
      aneurysm of the left ventricle (PIALV). During the preoperative period
      coronography, ventriculography, ultrasonic examination of the heart were made in
      all the patients, one-photon emission computed tomography with 123I-iodopent was
      used for radioisotope investigation of perfusion and metabolism of the
      myocardium. The presence of PIALV, diffuse atherosclerotic lesion of AIVA and
      viable myocardium in its basin was taken as an indication for autovenous plasty
      of the artery with the following shunt of the left intrathoracic artery and
      resection of PIALV.

PMID- 18050635
TI  - [Intracardial transplantation of mononuclear cells of the autologous bone marrow
      in complex treatment of patients with valvular heart diseases].
AB  - The authors present the first clinical experience with intramyocardial
      transplantation of the mononuclear fraction of cells of the autologous bone
      marrow in complex surgical treatment of 10 patients with valvular heart disease.
      The cellular transplantation was fulfilled intraoperatively when making a
      prosthetic mitral (5 patients) and aortal (5 patients) valves on the open heart
      under conditions of extracorporeal circulation. Simultaneously direct
      revascularization of the myocardium (aorto-coronary and mammary-coronary shunts)
      was performed in 4 patients (1--with a mitral and 3--with aortal heart diseases).
      An investigation of the results of the examination including ECG, EchoCG and
      investigation of the myocardium perfusion using one-photon emission computed
      tomography fulfilled in the early postoperative period and within 6-12 months
      after operation has shown that the cell cardiomyoplasty with mononuclear fraction
      of cells of the autologous bone marrow improves the myocardium perfusion,
      however, in the early postoperative period the appearance of transitory
      impairments of the heart rate is possible.

PMID- 18050636
TI  - [Resection of the left atrium in lung cancer].
AB  - An analysis of results of surgical treatment of 28 patients with lung cancer who
      underwent resection of the left atrium has shown that squamous cell cancer was
      diagnosed in 18 patients (64%), adenocarcinoma--in 5 (18%), dimorphous cancer--in
      2 (7%), mucoepidermoid cancer in 2 (7%), atypical carcinoid--in 1 patient (4%).
      The degree of regional lymphogenic spread of the tumor NO took place in 11
      patients (39%), N1--in 6 patients (22%), N2--in 11(39%). True invasion of the
      tumor to the left atrium myocardium took place in 20 patients (71%), involvement
      of the pulmonary vein orifices in the tumor process--in 8 (29%). Resection of the
      atrium was made using mechanical suturing apparatuses. The right side resections
      were fulfilled in 16 patients (57%), left side resections in 12 patients (43%).
      Pneumonectomy was fulfilled in 26 patients (93%), lobectomy--in 2 patients (7%).
      The operative interventions in five cases (18%) were estimated as microscopically
      non-radical (R1). The average time in the intensive care unit after operation was
      3 days (from 1 till 12), in the surgical thoracal department--18 days (from 13
      till 37). In the early postoperative period one patient died (4%), complications
      were noted in 5 patients (18%). The total one year survival was 69%, three year
      survival--39%, 5 year survival--17%. The survival median was 23 months. Resection
      of the left atrium in the selected lung cancer patients was not followed by
      growing operative lethality and the acceptable long term results were obtained.

PMID- 18050637
TI  - [Intraperitoneal pressure in acute small bowel obstruction].
AB  - The dynamics of intraperitoneal pressure (IPP) in acute small bowel obstruction
      was investigated in 50 patients with acute small bowel obstruction (ASBO), 25 men
      and 25 women aged from 16 through 82 years. The measurements were made in a
      nasogastral probe. Commissural ASBO was found in 24 (48%) patients, obturation-
      in 6 (12%), invagination--in 3 (6%) patients. Two groups of patients with high
      IPP (median 124 mm H2O) and low IPP (median 35 mm H2O) were established. The IPP
      level over 100 mm H2O, measured at admittance, can be considered an indication to
      operative treatment. Increased IPP makes the lethality risk of the patient
      higher. In case of non-complicated course of the postoperative period IPP is not
      higher than 10 mm H2O by the 2nd day. IPP higher than 30 mm H2O points to the
      development of intraperitoneal complications.

PMID- 18050638
TI  - [Laryngoscopy in patients undergoing thyroidectomy].
AB  - In a group of 365 patients undergoing thyroidectomy, the group of 21 patients
      with invasive thyroid malignancy was compared with 344 patients with benign
      thyroid disease or noninvasive cancers. It was shown that the method of indirect
      laryngoscopic examination was a simple and efficient method for detection of
      vocal cord paralysis and for the assessment of involvement of the surrounding
      tissues by the tumor. For the preoperative diagnosis of invasion of the recurrent
      nerve area such criteria as changed voice, results of CT and MRT were shown to be
      insufficiently reliable.

PMID- 18050639
TI  - [The use of blocked rods for pseudoarthroses and defects of the forearm bones].
AB  - The authors propose a method of reconstructive operation for treatment of
      pseudoarthroses and defects of the forearm bones. The method consists in
      performing bone plasty with a cylindrical hollow cortical-spongy autotransplant
      from the iliac crest in combination with the intramedullary osteosynthesis with
      block. The method can be recommended for practical use in traumatologic
      orthopedic hospitals having an electro-optical transducer.

PMID- 18050640
TI  - [Prophylactics of urological complications in patients with a vertebro-spinal
      trauma].
AB  - An original method of evacuation of urine from the bladder in spinal patients and
      patients with infravesical obstruction of different genesis (cystocuteneostoma)
      was worked out by the authors in experiments and introduced into clinical
      practice. A comparative analysis of the results of treatment of patients using
      ordinary methods and that developed by the authors has shown considerable
      advantages of the latter: less number of complications such as urethritis,
      urinary bladder calculi, pyelonephritis.

PMID- 18050641
TI  - [Defects of providing surgical care for closed injuries of the abdomen].
AB  - The aim of the work was to study defects of providing surgical care for closed
      injuries of the abdomen. An analysis of 19 reports of forensic medical
      examinations and 125 medical inpatients' cards helped to establish the leading
      causes of unfavorable outcomes of treatment and ways of improvement of the
      quality of providing medical care to such patients.

PMID- 18050642
TI  - [Surgical infection in children: new tendencies and principles].
AB  - The epidemiology, etiology, peculiarities of the clinical course of surgical
      infection (SI) and immune status in children aged from 0 to 15 years were
      investigated in 1970-2003. The results of the investigation are presented. The
      significance of evolution of the pathogenic agents and of the organism's
      resistance in the appearance of specific features of the clinical course of SI in
      childhood is discussed.

PMID- 18050643
TI  - [Choise of the strategy of treatment of patients over 60 years of age with a
      destructive cholecystitis complicated by abdominal sepsis].
AB  - The age of 242 patients with a destructive pathology of the gall-bladder
      complicated by abdominal sepsis was from 60 through 93 years. During the first
      day operations were made on 48 (19.83%) patients with peritonitis and systemic
      disorders, 10 patients died (43.47%). Within 1-5 days after conservative therapy
      194 (80.17%) patients were operated on, 13 patients died. The following symptoms
      of inflammation were observed: syndrome of systemic inflammatory reaction--in 13
      (5.37%) patients, sepsis--in 190 (78.51%), severe sepsis in 16 (6.61%), septic
      shock--in 23 (9.5%) patients.

PMID- 18050644
TI  - ["Preliminary" amputation for the irreversible ischemia of the lower
      extremities].
AB  - The author has summarized experiences of amputations of the shin and femur in 301
      patients for 10 years of work, has developed a surgical strategy for certain
      kinds of high amputations that allowed improving the results of amputations of
      lower extremities in 178 patients in the following three years. One of important
      factors in decreasing the number of purulent postoperative complications and
      lethality was using the method of "preliminary" amputation and reamputation.

PMID- 18050645
TI  - [Lipid peroxidation before and after amputation of the lower extremity in
      patients with atherosclerotic gangrene].
AB  - Activity of lipid peroxidation processes in blood was studied in 60 patients with
      atherosclerotic gangrene of the lower extremity subjected to amputation of the
      extremity in a prospective controlled investigation. Activation of the lipid
      peroxidation processes with a lower number and less activity of the antioxidant
      system enzymes was demonstrated in patients with severe critical ischemia of
      lower extremities. The operation trauma was followed by further stress of the
      system of free radical oxidation of lipids. The increased concentration of lipid
      peroxidation products with a decreased or low level of activity of the
      antioxidant system enzymes allows prognosis of the development of purulent
      complications at the early postoperative period.

PMID- 18050646
TI  - [The potential of surgical and bronchoscopic treatment of idiopathic scarry
      stenoses of the trachea].
AB  - Tracheolaryngeal resection is indicated for treatment of idiopathic scarry
      stenosis of the trachea with destruction of the cartilaginous tracheal semi-rings
      and cricoid cartilage. The proximity of anastomosis to the vocal folds does not
      influence the function of the vocal folds, if all technical peculiarities of the
      operation are observed. The bronchoscopic elimination of the scarry stenosis
      using laser dissection of the fibrous tissue, bougieurage and temporary
      endoprosthesis with a silicon T-shape stent is indicated in case of the saved
      integrity of the cartilaginous carcass of the trachea and larynx.

PMID- 18050647
TI  - [Minimally invasive interventions for acute cholecystitis complicated by
      mechanical jaundice in elderly and senile patients].
AB  - Results of the diagnosis and treatment of 165 patients with acute cholecystitis
      complicated by mechanical jaundice in elderly and senile age were analyzed. The
      method of endoscopic retrograde papillocholangiography used in 153 patients with
      acute cholecystitis complicated by mechanical jaundice is thought to be the most
      informative method of investigation of the bile ducts which allows determination
      of the exact cause and the level of disturbance of their patency. In 138 (83.6%)
      patients the cause of these complications was choledocholithiasis, in 18 (10.9%)
      isolated scarry strictures of the terminal part of the common bile duct and major
      duodenal papilla and in 9 patients (5.5%) a combination of these two diseases.
      Purulent cholangitis developed in 61 patients. Operations were fulfilled in 122
      patients at the second stage, in 38 patients it was laparoscopic cholecystectomy.
      The differentiated medico-diagnostic strategy for acute cholecystitis complicated
      by mechanical jaundice using a two-stage method of decompression and sanitation
      of the bile ducts is the most rational method of treatment of elderly and senile
      patients.

PMID- 18050648
TI  - [Comparative assessment of the Longo operation and suture ligation of the
      terminal branches of the upper rectal artery in treatment of chronic
      hemorrhoids].
AB  - The immediate and long-term results of treatment of patients with chronic
      hemorrhoids were compared in two groups of patients. The A. Longo method of
      operation was used in one group of patients, suture ligation of the distal
      branches of the superior rectum artery was used in the other group. The second
      method was shown to have some advantages over the Longo operation, but the long
      term results show greater effectiveness of the Longo method.

PMID- 18050649
TI  - [Necrosis of the round ligament of the liver].

PMID- 18050650
TI  - [Acute calculous cholecystitis: "protocols of diagnostics and treatment"].
AB  - The proposed protocols of diagnostics and treatment of acute calculous
      cholecystitis were developed in St. Petersburg Djanelidze Research Institute of
      Emergency Medicine where the problems of treatment of patients with acute
      inflammatory diseases of the bile ducts are investigated in collaboration with
      the leading experts in this field in Saint Petersburg and Leningradskaya oblast.
      The protocols are based on the collective experience of many authors, who
      realized in their work different strategic directives and methods of treatment of
      complicated forms of cholelithiasis and nevertheless came to similar conclusions.
      They contain recent developments of the organization and carrying out diagnostic
      and medical measures for patients with this pathology which could improve results
      of treatment of this not simple category of patients.

PMID- 18050651
TI  - [Pathogenesis, diagnostics and treatment of chyloperitoneum].

PMID- 18050652
TI  - [Methods of diagnostics of intestine paresis in acute surgical diseases of organs
      of the abdominal cavity].

PMID- 18050653
TI  - [Extracapsular extension as an unfavorable factor of prognosis in cancer of the
      prostate].

PMID- 18050654
TI  - [Approaches to elimination of postoperative pain].

PMID- 18050655
TI  - [Artificial inhibition of the complement system].
AB  - A great number of natural substances affect the complement system in addition to
      its natural regulators. Among the complement effectors, the most important are
      inhibitors of the activation cascade. The necessity of searching for preparations
      capable of a purposeful effect on complement by inhibition of single stages of
      the activation cascade and without influence on its other functions is connected
      with the current importance of use in medicine of novel therapeutic regulators of
      the complement system. Important directions are the search for complement
      inhibitors that (a) interfere with the rejection of transplants; (b) can replace
      C1 inhibitor in hereditary angioedema, and (c) have a high anti-inflammatory
      activity in the therapy of rheumatic diseases, diabetes, and other autoimmune
      disorders. It is expedient to use the available techniques for the directed
      detection of the action of medicinal substances on complement, which allow the
      determination of their action on the complement system at various stages of the
      cascade of its activation.

PMID- 18050656
TI  - [Ion channels of various types induced in lipid membranes by gramicidin A
      derivatives carrying a cationic sequence at their C-termini].
AB  - The channel-forming activity of gramicidin A derivatives carrying positively
      charged amino acid sequences at their C-termini was studied on planar bilayer
      lipid membranes and liposomes. We showed previously that, at low concentrations,
      these peptides form classical cation-selective pores typical of gramicidin A,
      whereas, at high concentrations, they form large nonselective pores. The ability
      of the peptides to form nonselective pores, which was determined by the efflux of
      carboxyfluorescein, an organic dye, from liposomes, decreased substantially as
      the length of the gramicidin fragment in the series of cationic analogues was
      truncated. CD spectra showed that large pores are formed by peptides having both
      beta6.3 single-stranded and beta5.6 double-stranded helical conformations of the
      gramicidin fragment, with the C-terminal cationic sequence being extended. The
      dimerization of the peptides by the oxidation of the terminal cysteine promoted
      the formation of nonselective pores. It was shown that nonselective pores are not
      formed in membranes of erythrocytes, which may indicate a dependence of the
      channel-forming ability on the membrane type. The results may be of interest for
      the directed synthesis of peptides with antibacterial activity.

PMID- 18050657
TI  - [Duodenase activates rat peritoneal mast cells via protease-activated receptors
      of type 1].
AB  - It was found that duodenase, a serine protease from the bovine duodenum,
      activates rat peritoneal mast cells (PMC) in vitro presumably via protease
      activated receptors (PARs). Like thrombin (a serine protease from the blood
      coagulation system) and the PAR1 agonist peptide (PAR1-AP), duodenase was shown
      to accelerate the secretion of beta-hexosaminidase (a marker of cell
      degranulation) by PMC in a dose-dependent manner. The blockage of the proteolytic
      activity of duodenase toward the substrate Tos-Gly-Pro-Lys-pNA by the soybean
      Bauman-Birk protease inhibitor substantially reduced (by 40%) the ability of
      duodenase to stimulate the secretory activity of PMC. Pretreatment of PMC with
      duodenase decreased the beta-hexosaminidase secretion induced by thrombin and
      PAR1-AP by 35 and 41.7%, respectively, and abolished the antiinflammatory effect
      of activated protein C. At the same time, pretreatment of PMC with duodenase did
      not affect the secretion of beta-hexosaminidase induced by compound 48/80, a
      nonspecific degranulator of mast cells. Duodenase, unlike PAR1-AP (30-100
      microM), in a broad concentration range (10-100 nM) did not induce aggregation of
      human platelets, but suppressed the platelet aggregation elicited by PAR1-AP.

PMID- 18050659
TI  - [Positively charged acyl derivatives of carbohydrates as promising transfection
      agents].
AB  - A convenient approach to the synthesis of mono- and polycationic glycolipid
      amphiphiles is suggested. The compounds obtained can be used for study of the
      structure-activity relationship and determination of the effect of hydrophobic
      and cationic domains on transfection efficiency.

PMID- 18050658
TI  - [Isosteric triphosphonate analogues of dNTP: synthesis and substrate properties
      toward various DNA polymerases].
AB  - Isosteric triphosphonate derivatives of 2',3'-dideoxy-2',3'-didehydroadenosine
      and 3'-deoxy-2',3'-didehydrothymidine and their beta,gamma-substituted analogues
      were synthesized. Their substrate properties toward a number of reverse
      transcriptases of the human immunodeficiency and bird myeloblastosis viruses,
      human DNA polymerases alpha and beta, and the Klenow fragment of Escherichia coli
      DNA polymerase I were studied.

PMID- 18050660
TI  - [Depth-dependent investigation of the apolar zone of lipid membranes using a
      series of fluorescent probes, Me4-BODIPY-8-labeled phosphatidylcholines].
AB  - A series of lipid probes, phosphatidylcholines labeled with Me4-BODIPY-8 (4,4
      difluoro-1,3,5,7- tetramethyl-4-bora-3a,4a-diaza-s-indacen-8-yl) fluorophore
      attached to the end of an acyl residue at different distances from the polar
      head, were used as depth-dependent probes for the apolar zone of model membrane
      systems, large unilamellar vesicles (LUVs). Data on the anisotropy of probe
      fluorescence demonstrated different mobility profiles for the fluorophore
      microenvironment in LUVs of different composition at various temperatures, which
      indicates a high sensitivity of these probes as tools for studying membrane
      systems. An interesting anomaly was observed for LUVs from
      dimiristoylphosphatidylcholine (DMPC) or from a DMPC-cholesterol mixture: the
      anisotropy of the fluorophore located near the bilayer center is larger than that
      of the fluorophore located further from the center; i.e., the mobility of the
      microenvironment is lower in the first case. This anomaly is supposed to result
      from the penetration of the unlabeled long chain of the probes into the opposite
      bilayer leaflet. Such a possibility should be taken into account in constructing
      fluorescent probes and interpreting the results.

PMID- 18050661
TI  - [Development of a rapid method for the detection of prostate-specific antigen by
      immunochromatography].
AB  - A single-step qualitative rapid test for the determination of prostate-specific
      antigen (PSA) in samples of human blood serum by immunochromatography using a
      complex of colloidal gold with monoclonal antibodies to PSA as the detection
      agent was developed. The determination limit for PSA in serum blood samples is 10
      ng/ml; the analysis time, 15-25 min; the sensitivity of the method, 100%; and its
      specificity, 92.5%.

PMID- 18050662
TI  - [Regioselectivity of ferulic acid polymerization catalyzed by oxidases].
AB  - Enzymatic oxidation of ferulic acid catalyzed by oxidases (laccase and
      peroxidase) was carried out. Ferulic acid was shown to be subjected to oxidative
      processes leading to the formation of oligomeric and polymeric structures. The
      polymer formation takes place due to the formation of CAr-CAr-, and CAr-O-CAr
      bonds, as well as due to reactions of opening of the propane chain double bond.
      Different dynamic conditions of the enzymatic reactions were used to study the
      effects of conditions on the biosynthesis in vitro of some dehydropolymers: the
      method of dropwise mixing (endwise polymers) and a single addition (bulk
      polymers). The chemical structures of the resulting compounds were examined by
      the methods of IR, 1H NMR, and 13N NMR spectroscopy. Differences in the
      quantitative ratio of structural fragments in a polymer cause changes in its
      thermal characteristics.

PMID- 18050663
TI  - [Polycationic catalysts for phosphodiester bond cleavage on the basis of 1,4
      diazabicyclo[2.2.2]octane].
AB  - A number of tetracationic compounds capable of phosphodiester bond cleavage
      within a 21 -membered ribooligonucleotide were designed and synthesized. The
      artificial ribonucleases represent two residues of quaternized 1,4
      diazabicyclo[2.2.2]octane bearing alkyl substituents of various lengths and
      connected with a rigid linker. The efficiency of cleavage of phosphodiester bonds
      in an RNA target depends on the linker structure and the length of alkyl
      substituent.

PMID- 18050664
TI  - [Oligonucleotide conjugates with minor groove ligands as probes for hybridization
      microarray chips].
AB  - A possibility of using oligonucleotide conjugates with minor groove ligands as
      probes for hybridization microarray chips was studied. The oligonucleotide
      conjugates contain a hairpin ligand (MGB) composed of two tripyrrolcarboxamide
      residues with an aminocaproic acid residue as a linker and bound to the
      oligonucleotide duplex AT tract in a site-specific manner. We used as (5'-3')
      probes GACAAGAp, GACAAAAp, GACAAGA-MGB, and GACAAAA-MGB. The oligonucleotides
      labeled with Cy3 cyanine dye, Cy3-ACTAATTTTGTC and Cy3-ACTAATCTTGTC, were used as
      targets. The maximal MGB effect on the fluorescence level of microarray chip
      spots, which caused its fourfold increase as compared with the initial unmodified
      duplex, was observed for the duplex containing only AT pairs in the ligand
      binding site. The presence of A-C and G-T mutations in the binding site
      (imperfect duplexes) or a C-G pair (perfect duplex) affects the change in
      fluorescence level to a considerably lesser degree.

PMID- 18050665
TI  - [Study of the mechanism of Ras-dva small GTPase intracellular localization].
AB  - An analysis of amino acid sequences of small GTPases of the Ras-dva family
      allowed us to determine the C-terminal prenylation motif, which could be
      responsible for the membrane localization of these proteins. We demonstrated
      using in vivo EGFP tracing that the Ras-dva small GTPases from Xenopus laevis
      embryo cells and NIH-3T3 fibroblasts are localized on both plasma membranes and
      endomembranes (the endoplasmic reticulum, the Golgi apparatus, and vesicles). At
      the same time, the replacement of the Cys residue, the SH group of which must be
      theoretically farnesylated, in the C-terminal prenylation motif of the Ras-dva
      small GTPase by the Ser residue prevented the membrane localization of the
      protein. These results indicate that the C-terminal prenylation site is critical
      for the membrane localization of small Ras-dva GTPases.

PMID- 18050666
TI  - [The effects of age on insulin sensitivity and insulin secretion in Japanese
      subjects with normal glucose tolerance].
AB  - The prevalence of impaired glucose tolerance and type 2 diabetes increases with
      age. However, controversial results have been reported in regard to which has a
      greater influence on the deterioration of glucose tolerance with age, namely
      impaired insulin sensitivity or impaired insulin secretion. The conflicting
      results may arise mainly from differences in the evaluation of insulin secretion
      and insulin sensitivity, and from differences in the physical composition and the
      ethnicity of the study subjects. We therefore selected Japanese subjects, between
      20 and 80 years of age, with normal glucose tolerance (NGT) and with a body mass
      index (BMI) below 25.0 kg/m2, and then examined the subject's insulin sensitivity
      based on the indices of a homeostasis model assessment-insulin resistance index
      (HOMA-IR) and ISI composite (ISI), and beta-cell function by these of HOMA-beta,
      AUC I/G(0-120), an insulinogenic index (deltaI30/deltaG30), and then
      (deltaI30/deltaG30)/HOMA-IR derived from a 75 g-oral glucose tolerance test
      (OGTT). The subjects were divided into the six subgroups according to sex and
      age, below age 30, between ages 30 and 49, and equal to and over age 50. Both
      HOMA-IR and the ISI showed no differences across the range of age and sex. HOMA
      beta decreased with age, and AUC I/G(0-120) decreased in the elderly. No change
      was observed in deltaI30/deltaG30 across the age range in men, however
      deltaI30/deltaG30/HOMA-IR, the index of the early phase insulin secretion
      adjusted for insulin sensitivity, decreased with age in both men and women. These
      data indicated that aging itself had no effect on insulin sensitivity, while
      insulin secretion in both the early and late phase during the OGTT deteriorated
      with age even within the NGT subjects.

PMID- 18050667
TI  - [Clinical usefulness for measurement of plasma brain natriuretic peptide in
      diabetic patients].
AB  - Plasma brain natriutetic peptide (BNP) concentrations in type 2 diabetic patients
      were measured by newly developed enzyme immunoassay, and their clinical
      application was evaluated. Precision of the measurement system was satisfactory
      for clinical use, and the value obtained by this system had good correlation to
      that by radioimmunoassay. Tubes containing NaF in addition to EDTA, usually used
      for measurement of plasma glucose and HbA1c in diabetic patients, could be used
      for the collection of plasma sample. In 133 type 2 diabetic patients who had no
      symptom for heart failure, plasma BNP was elevated in those with ischemic heart
      disease and it was also significantly elevated even in the patients who had no
      ischemic change on double Master two-step exercise testing than that in control
      subjects. In 52 patients receiving the examination by cardiosonography, plasma
      BNP levels significantly correlated to the left ventricular mass index, and also
      had a significant correlation to peak flow velocity in early diastole/peak flow
      velocity in late diastole (E/A) ratio, one of a simple index for an asymptomatic
      diastolic heart failure. Multiple logistic regression analysis revealed that age
      and coronary heart disease were extracted as a significant valuable for plasma
      BNP level in type 2 diabetic patients. These results suggest that measurement of
      plasma BNP in type 2 diabetic patients was useful as a screening method for
      evaluating the latent deterioration of heart function such as asymptomatic
      ischemic heart disease.

PMID- 18050668
TI  - Development of a quantitative evaluation system for motor control using wrist
      movements--an analysis of movement disorders in patients with cerebellar
      diseases.
AB  - In this study, we developed a new system for quantitative evaluation of the wrist
      movement. We designed this system to analyze the causal relationship between
      movement disorders and abnormal muscle activities. In addition, this system was
      also designed to be non-invasive and used handily at the bedside. We tested this
      system for analysis of movement disorders in the cerebellar patients. As an
      experimental task, we asked subjects to perform step-tracking wrist movements
      with a manipulandum, and simultaneously recorded wrist joint movements and muscle
      activities of four wrist prime movers with surface electrodes. The participants
      included eight patients with cerebellar diseases and eight normal controls.
      First, we made quantitative analysis of movement kinematics in the cerebellar
      patients in terms of accuracy and directional deviation of wrist movements. Then
      we examined how well the wrist movement could be explained with the activities of
      the four prime movers. Specifically, we compared the wrist joint torque
      calculated from the movement of the wrist (kinematic torque) and the wrist joint
      torque estimated from the muscle activities (muscle torque). Then we evaluated
      match between the two. Our surprising observation was that there were very high
      correlations between the kinematic torque and the muscle torque for both normal
      controls and cerebellar patients. Correlation coefficients R for normal controls
      were 0.85 +/- 0.06 for X-axis component and 0.78 +/- 0.09 for Y-axis component.
      On the other hand, correlation coefficients R for cerebellar patients were 0.78
      +/- 0.11 for X-axis component and 0.78 +/- 0.1 for Y-axis component. These
      results strongly suggested that there were enough information in the activities
      of the four muscles to explain the position, speed and acceleration of the wrist
      joint. In other words, with our system, it is possible to identify causal
      abnormality of muscle activities for movement disorders. Therefore, it is
      possible with our system to analyze movement disorders at a motor command level.

PMID- 18050669
TI  - In situ hybridization with novel biotinyl-tyramide: fundamental studies and its
      utility of the detection of human papilloma virus in tissue sections.
AB  - We developed an in situ hybridization (ISH) method with a higher sensitivity and
      less background staining than the generally used catalyzed reporter deposition
      amplification method of in situ hybridization (CARD-ISH). The characteristics of
      this method are follows: sections heated in citrate buffer (pH6.0) containing
      0.1% Triton X-100 showed the strongest signals, and a well-preserved morphology.
      The strongest signals were observed when borate buffer of biotinyl-tyramide stock
      and phosphate buffer of working solution were changed to Tris-HCl buffer.
      Compared with hematoxylin counter staining, alcian blue counter staining made it
      easier to identify dot, diffuse, and mixed type signals, respectively. Thus, we
      were able to clearly detect positive signals in the SiHa cell line with 1-2
      copies of the integrated human papilloma virus-16 (HPV-16) gene, and in formalin
      fixed, paraffin-embedded cervical lesion specimens for the HPV-16 gene.

PMID- 18050670
TI  - [Anaerobiospirillum succiniciproducens septicemia].
AB  - We report the first case of septicemia caused by anaerobic spiral-shaped Gram
      negative bacilli, Anaerobiospirillum succiniciproducens in Japan. A 71-year-old
      male who had been suffered from terminal stage of liver cirrhosis and
      hepatocelluler carcinoma was admitted to our hospital for his symptoms of general
      malaise and increasing ascites on September 1, 2004. He developed diarrhea seven
      times a day on the eighth hospital day and had fever of 38.7 degrees C with WBC
      12,600/microl and CRP 6.6 mg/dl on the next day. Blood culture grew Gram negative
      spiral bacilli. We initially could not identify the offending bacterium that
      resembled to Campyrobacter morphologically using commercially available
      indentification kits. However, 16SrRNA sequencing test revealed 100%
      compatibility with Anaerobiospirillum succiniciproducens.

PMID- 18050671
TI  - [Preanalytical issues].
AB  - Preanalytical issues in laboratory medicine have been recognized to be important
      but not so much effort have been focused to them. Urinalysis is one of the most
      susceptible examinations to preanalytical issues because urine samples are
      collected by patients themselves and so is stool examination too. Midstream urine
      catch is well-known appropriate procedure for many urinalysis. Surface scratching
      is an appropriate method of stool occult blood testing for colorectal cancer and
      also strategies to avoid the contact of stool with toilet water is another
      important technique. We also report a case of abnormal results of creatinine
      clearance (Ccr) caused by the urine collection apparatus as an example of
      preanalytical issue.

PMID- 18050672
TI  - [Microbiology laboratory as a base of information sending].
AB  - The goal of our microbiology laboratory is to provide an accurate microbiological
      result and a useful information for every healthcare workers (HCWs). For this
      purpose, we were trying to do several activities, such as improving the work-flow
      of microbiology testings, starting 365-day-open microbiology tests, providing
      some training courses of microbiology and sending many useful informations about
      infectious diseases and infection control. Before these activities, we needed
      another 5 microbiology technicians beside 3 technicians and had started the
      program to educate them. We have successfully finished it and enabled all plans
      begin in April, 2005. Since then we are open for 365 days and also sending HCWs
      many newsletters for performing effective microbiological testings via the intra
      network system and having lectures for both doctors and nurses, especially for
      new resident doctors at the orientation. We had also the training course for
      certified infection control nurses and accepted two technicians from Africa, who
      came to study a basic microbiology via JICA. These activities have enabled every
      technician not only to report and analyze microbiological test result effectively
      but also to improve writing and presentation skills. Through these activities all
      technicians have realized that accurate and rapid information from a microbiology
      laboratory is a key to treat patients with infectious diseases and improve their
      prognosis. It is suggested that skill-up of technicians lead to report an
      accurate result in microbiology and at the same time improve the attitude for
      their job.

PMID- 18050673
TI  - [Thrombotic tendency and laboratory medicine in metabolic syndrome].
AB  - Metabolic syndrome is defined as a complex of hypertriglyceride, insulin
      resistance, hypertension, and accumulation of visceral fat. This syndrome is
      often accompanied by thrombotic diseases (e.g., myocardial infarction, cerebral
      infarction), but the mechanism (s) of thrombotic tendency has not yet been
      elucidated. Plasminogen activator inhibitor-1 (PAI-1), a principal regulator of
      fibrinolytic system, plays a pathological role in the development of thrombosis
      and cardiovascular diseases. PAI-1 is regarded to be one of adipocytokines
      because it is produced and secreted by adipocytes. The expression of PAI-1 in
      adipocytes is upregulated by insulin, TNF-alpha, and TGF-beta, suggesting that it
      is relevant to insulin resistance. PAI-1 antigen level in plasma is elevated in
      obese subjects and increases in parallel with their BMI and visceral fat. It was
      experimentally revealed that PAI-1 expression in adipose tissue was dramatically
      increased in genetically obese mice and abundant expression of PAI-1 was
      localized to adipocytes in vivo. PAI-1 deficient mice were resistant to high fat
      diet-induced body weight gain, adipose accumulation, and insulin resistance in
      association with lack of decreased expression of adiponectin. Taken together, PAI
      1 may be a key molecule to develop obesity and insulin resistance as well as
      thrombotic diseases. It is possible to prevent thrombotic complications and
      cardiovascular diseases in obese patients by controlling PAI-1 expression and
      function. Each pathology included in metabolic syndrome could stimulate PAI-1
      expression, and thus, PAI-1 would be a good marker of progression of metabolic
      syndrome itself and of risk for thrombotic cardiovascular diseases as well.

PMID- 18050674
TI  - [New surgical technologies in oncology].
AB  - Despite new efficient methods of pharmaco- and radiotherapy, surgery is still
      applied to most patients with malignant tumors as the main treatment. Rational
      definition of indications to a surgical intervention based upon precise
      morphological verification of the diagnosis and correct staging is half a battle
      of surgical success. When planning the time and volume of surgery, its aim
      (whether it is radical, palliative, or reconstructive intervention) should be
      understood very clearly. The ideology of oncosurgery has changed to a great
      extent. On the one hand, wide clinical application of contemporary imaging
      techniques (CT, MRI, and PET) has resulted in more frequent detection of non
      advanced tumors. Another aspect of present-day big oncosurgery is the application
      of advanced surgical techniques as well as the development of broad resection
      techniques and methods of en bloc removal of locally advanced tumors from
      different locations. By examples of thoracoabdominal tumors (neoblastomas of the
      bronchi, mediastinum, stomach, and kidney) and bone tumors the author considers
      the main aspects of modern operative strategy in oncology.

PMID- 18050675
TI  - [The development of radiotherapeutic techniques at the beginning of the 21st
      century in Blokhin Russian Oncological Research Center of Russian Academy of
      Medical Sciences].
AB  - The article describes the development of radiotherapeutic techniques in Blokhin
      Russian Oncological Scientific Center of Russian Academy of Medical Sciences at
      the end of the 20th and the beginning of the 21st centuries. Such developmental
      directions in radiation oncology as the development of non-conventional modes of
      radiation dose fractioning, the development of new radiotherapeutic techniques
      based on volumetric 3D dosimetric radiotherapy planning, the perfection of
      combined (contact plus distant) radiotherapy, the use of multidirectional
      radiomodifying agents, the application of radiotherapy as a part of combined and
      complex treatment with chemotherapy and surgery in different tumoral sensitivity
      to conservative treatment, are considered in the article. Immediate and long-term
      results achieved at the institution by the use of radiotherapy alone or as a part
      of combined or complex treatment in cases with certain malignant tumor
      localizations are described.

PMID- 18050676
TI  - [High technologies in radiodiagnostics: possibilities and prospects].
AB  - Diagnostic radiology includes several basic techniques such as conventional
      radiography, computed tomography, magnetic resonance imaging, radionuclide study,
      ultrasonography, and positron emission tomography as the most important methods.
      Radiological screening procedures or preclinical diagnostic techniques, as well
      as interventional radiological procedures, are being used more and more widely in
      clinical medicine. The integration and combination of different technologies, the
      introduction of digital diagnostic technologies, and the creation of radiological
      information systems on their basis are important factors increasing diagnostic
      efficiency. Improved technologies make it possible to change diagnostic tactics
      in the majority of diseases; the diagnostic process shortens because preference
      is given to most informative methods. Intensive technological development
      requires changes in the arrangement of radiologists' work.

PMID- 18050677
TI  - [Complex radiodiagnostics of non-Hodgkin's thoracic or abdominal lymphoma in
      children].
AB  - The clinical manifestations of non-Hodgkin's lymphoma (NHL)-associated lesions of
      thoracic or abdominal organs and tissues, and the results of application of
      radiodiagnostic techniques in 414 children with the disease, were analyzed. The
      results of the analysis of radiological and ultrasonographic manifestations of
      thoracic and abdominal lesions in children with NHL make it possible to perform
      more effective early diagnostics of the disease in wide healthcare practice.
      Also, these results confirm the mandatory character of the general principle of
      pediatric tumor diagnosis, i.e. complex application of clinical, morphological,
      endoscopic, laboratory, and radiological techniques, including routine X-ray
      diagnostics, computed tomography, ultrasound tomography, and radioisotopic
      examination.

PMID- 18050678
TI  - [Innovation approaches to treatment of children with malignant tumors of the
      musculoskeletal system].
AB  - The Department of Musculoskeletal System Tumors was formed in November 1989
      within Research Institute of Pediatric Oncology and Hematology of N. N. Blokhin
      Russian Oncological Scientific Center of Russian Academy of Medical Sciences.
      Treatment is carried out with the newest achievements in oncopediatrics applied;
      priority is given to limb-sparing techniques. The total 5-year survival rate of
      patients with Ewing's sarcoma is 65.6%, the total 2-year survival rate of
      patients with soft tissue sarcomas is 62.2%, and the total 2-year survival rate
      of children with osteosarcoma is 76%. Study of complications and side-effects of
      chemotherapy, as well as the development of methods of their prevention and
      correction, present a separate direction in the department's activity. In 1999,
      the team of the institution's researchers was awarded Russian Federation State
      Prize for outstanding scientific achievements in the work Development and
      Clinical Application of Combined Methods of Treatment of Osteogenic Sarcoma. In
      2003 and 2004, leading researcher N. M. Ivanova was awarded the institution's
      diplomas as a part of Biotech prize for the development of new methods of
      treatment of malignant tumors in children.

PMID- 18050679
TI  - [The pharmacological strategy of overcoming the phenotype of the multiple
      pharmacoresistance of non-small-cell lung cancer].
AB  - The authors discuss literature data and the results of their own many-year
      research into molecular markers of multiple pharmacoresistance associated with
      the function of ABC-transporters (MDRABC) from the point of view of their
      clinical significance. They consider the evolution of views on the mechanism of
      functioning and intracellular localization of ABC-transporters in normal and
      tumoral cells, in particular, the role of these transport proteins in the
      protection of nuclear targets from toxic agents, including antitumoral
      preparations. By the example of non-small-cell lung cancer (NSCLC) the authors
      critically analyze the reasons why data on the frequency of ABC-transporters
      expression in human solid tumors and on their prognostic value are inconsistent.
      The article contains a detailed analysis of the results of the authors' own
      research into the activity of ABC-transporters in NSCLC, in which the frequency
      of expression and co-expression of different transport proteins (including Pgp
      and MRP) is defined and new characteristics and mechanisms of the regulation of
      the functioning of MDRABC molecular markers are revealed. A methodical approach
      to routine characterization of MDRABC phenotype in NSCLC is offered. The main
      directions of pharmacological strategy of overcoming the multiple
      pharmacoresistance of NSCLC are formulated.

PMID- 18050680
TI  - [Multiple medication resistance of apoptosis-resistant tumoral cells].
AB  - A4 clone cells, received by CD95-mediated selection from the parental line of
      Jurkat T-lymphoblast human leukosis, lost their ability of apoptosis as a result
      of programmed cell death mechanism breakdown. The complex of their acquired
      phenotypic properties meets tumor progression criteria: oxidative stress
      resistance, active immune suppression, and low requirement for growth factors.
      The loss of A4 cell ability of apoptosis is accompanied by acquisition of the
      phenotype of multiple medication resistance to a wide spectrum of antineoplastic
      chemotherapeutic drugs and cytotoxins.

PMID- 18050681
TI  - [Cancer vaccinotherapy: from the experiment to clinical application].
AB  - Methods of cancer immunotherapy with dendritic cell-based vaccines, activated
      outside the organism, as well as techniques employing genetically modified whole
      cell antitumoral vaccines, transfected by cytokine gens and stimulating the
      patient's dendritic cell stimulation in vivo, have been developed in Russian
      Oncological Research Center. Phase 1 clinical trials of dendritic cell vaccine in
      patients with disseminated melanoma and colon cancer have been carried out. The
      treatment is well-tolerated; significant adverse effects are absent. Moderate
      clinical efficacy and immune activation have been noted. Preclinical and phase 1
      clinical studies of genetically modified vaccines also demonstrate the safety of
      this treatment and its ability to activate antitumoral immune response. Both
      vaccines are promising as subjects of rationally planned clinical trials of the
      efficacy of this treatment.

PMID- 18050682
TI  - [Method of forensic medical examination of pathological changes caused by
      undernutrition].
AB  - A method of forensic medical examination of pathological changes caused by
      undernutrition is proposed. The method consists of several stages including an
      algorithm of detection of diagnostic characters of alimentary dystrophy and
      deficiency of body weight. Use of this method will assist in observance of the
      law about reliability of expert reports.

PMID- 18050683
TI  - [Using some modern mathematical models of postmortem cooling of the human body
      for the time of death determination].
AB  - Mathematical questions of data errors of modern thermometrical models of
      postmortem cooling of the human body are considered. The main diagnostic areas
      used for thermometry are analyzed to minimize these data errors. The authors
      propose practical recommendations to decrease data errors of determination of
      prescription of death coming.

PMID- 18050684
TI  - [Necessity of unified approach to on-site corpse inspection].
AB  - The authors give general analysis of the work of 51-th Territorial Bureau of RF
      Forensic-Medical Expert Examination for on-site corpse inspection and detailed
      analysis of the work of the Moscow operative investigation group during 2006. The
      corpse inspection quality and effectiveness depend on timely and complete
      realization of organizing preparatory measures ensuring optimal conditions for
      the inspection. Adoption of new and use of existing scientific and technical
      methods make it possible to increase the reliability of conclusions regarding
      prescription of death coming.

PMID- 18050685
TI  - [Forensic-medical assessment of diaphysis fractures in childhood].
AB  - The authors established that special structure of bones in childhood have a
      significant influence on the fractures of long tubular bones. The formation of
      unusual fractures shows it. Under condition of low speed of bending in the area
      of fracture many microfissures are formed, which leads to structural failure of
      intraosseous microcirculation and osteocytes.

PMID- 18050686
TI  - [Gender determination based on osteometric characteristics of the upper and lower
      extremities by discriminant analysis].
AB  - The authors studied the osteological collection of the Chair of Antropology of
      the Moscow State University. The results of measurement of length of long tubular
      bones and articular parts of scapula and pelvis were statistically treated. The
      complex of discriminant models calculated by the Fisher's method is recommended
      for the sex identification. The diagnostic accuracy is 74 - 83.5% (separated
      bones) and 85.7 - 95.2% (complex of bones of upper and lower extremities).

PMID- 18050687
TI  - [Personality identification of unidentified corps in the morgue].
AB  - In order to identify unidentified corps in morgue, new possibilities of
      craniofascial identification based on use of the dental status and facial
      skeleton asymmetry were studied. An original computer program was created. The
      program contains all identification signs and information search base making it
      possible to improve corpse authentication and identification.

PMID- 18050688
TI  - [Combined use of molecular genetic technologies to identify the Russian citizens
      died during tsunami in Thailand].
AB  - Main stages, methodological aspects and practical results of molecular genetic
      research to identify the citizens of Russia died during tsunami in Thailand are
      considered.

PMID- 18050689
TI  - [Analysis of elemental composition of bone tissue by the method of laser mass
      spectrometry to diagnose of human medico-biological characteristics].
AB  - The results of analysis of elemental composition of human bone tissue by the
      method of laser mass spectrometry are published for the first time. This method
      makes it possible to detect about 20 elements of bone tissue at once.
      Quantitative analysis of 1 microgram/gram of an element contained in bone tissue
      is sufficient to diagnose of human medico-biological characteristics by this
      method.

PMID- 18050690
TI  - [Determination of lithium content in human biological objects (liver, kidney) by
      the method of flame photometry].
AB  - The authors give a method of determination of the content of lithium in
      biological objects (liver, kidney) by the method of flame photometry. It is
      possible to use this method in forensic medicine in cases of acute intoxication.

PMID- 18050691
TI  - [Characteristics of dipyridamol isolation from biological material].
AB  - Acetone is proposed as an isolating agent for extraction of dipyridamolum from
      biological material. Optimal conditions of isolating dipyridamolum from human
      cadaveric liver tissue with acetone are determined and quantitative estimation of
      isolation results is provided.

PMID- 18050693
TI  - [The urban environment and human health].

PMID- 18050692
TI  - [Modern foreign car safety systems and their forensic-medical significance].
AB  - The author gives a characteristic of active and passive security systems
      installed in cars of foreign production. These security systems significantly
      modify the classic car trauma character decreasing frequency of occurrence and
      dimensions of specific and typical injuries. A new approach based on the theory
      of probability to estimate these injuries is required. The most common active and
      passive security systems are described in the article; their principles of
      operation and influence on the trauma character are estimated.

PMID- 18050694
TI  - [Topical problems of the comprehensive hygienic characterization of urban
      environmental factors and their influence on the population's health].
AB  - The authors consider the topical problems of the influence of urban environmental
      factors (the quality of drinking water, the pollution of the ambient and dwelling
      airs and soil) on the health of residents in the urbanized areas. They show it
      necessary to apply a comprehensive approach to studying and analyzing the
      influence of a large number of interrelated factors on the population's health
      and its vulnerable subgroups, by employing the current sensitive biomedical
      studies, as well as to develop and introduce noninvasive techniques for the early
      diagnosis of environment-induced diseases.

PMID- 18050695
TI  - [Topical aspects of dwelling environmental hygiene and ways of their solution].

PMID- 18050696
TI  - [Hyienic assessment of the formation of a total risk to the population's health
      in urbanized areas].

PMID- 18050697
TI  - [Complex issues of health risk management in solving the problems of sanitary-and
      epidemic well-being provision at the municipal level].

PMID- 18050698
TI  - [Current problems in the assessment of health risks and damages from the
      influence of environmental factors].
AB  - In the past decade, a great number of risk assessment projects have been
      implemented; experience in using the risk-assessing methodology in sociohygienic
      monitoring, in the hygienic evaluation of a possible impact of new or rebuilt
      plants on human health, and in the estimation of natural and cost damages from
      the influence of environmental factors has been gained. Along with the legal
      aspects of using the risk-assessing methodology, there is a diversity of urgent
      and unsolved problems: a discrepancy between the hygienic standards and the risk
      assessing criteria established in our country, recommended by international
      organizations, or used in the leading countries of the world; evaluation of
      exposures; availability of data on exposures in both individual regions and
      Russia as whole; development of methods for the assessment of damages and for the
      comparative assessment of risks, including such indices and their value terms as
      lost life years and life years with consideration of the severity of
      abnormalities.

PMID- 18050699
TI  - [Structural and energy changes in water and its biological activity].
AB  - The authors consider the structural and energy changes occurring in water during
      its treatment using physical methods and the impact of these conditions on
      metabolic processes. Emphasis is laid on the necessity of putting the integral
      indices, considering the magnitude of changes in the structural and energetic
      conditions of water and its biological activity, into practice.

PMID- 18050700
TI  - [Improving the standard and methodological basis for bacteriological monitoring
      the quality of drinking water].
AB  - The paper presents materials to provide a scientific rationale for the
      microbiological parameters enhancing the efficiency of drinking water quality
      control from the point of view of reliability in the provision of epidemic water
      consumption safety (coliform bacteria being identified by the glucose index; E.
      coli). Based on the criterion assessment of the significance of microbial water
      contamination in relation to morbidity rates, the authors have been developed
      bacteriological standards--the absence of microorganisms in a 300-ml water
      sample. Evidence is provided for the epidemically significant level--more than 2
      CFU of coliform bacteria in 100 ml. A rapid determination procedure has been
      substantiated in the experimental studies of the effects of oxidase reagents on
      the viability and biochemical properties of E. coli bacteria. In search for
      current technologies for membrane filtration, experimental rationale has been
      made for the possibility of using track membranes for sanitary and
      bacteriological water analyses.

PMID- 18050701
TI  - [Oil pollution of a number of Moscow residential and recreational areas].
AB  - The soils of residential areas were studied in different Moscow districts
      differing in the level of a man-caused load. Oil pollution was estimated by the
      soil content of oil hydrocarbons. A correlation was established between the
      levels of hydrocarbons and the sanitary ill-being of the city's soils.

PMID- 18050702
TI  - [Analyzing the population's health risks from the influence of environmental
      factors of various nature in vicinity of the Siberian chemical complex].
AB  - The paper provides the results of calculating the risks to human health in the
      cities of Seversk and Tomsk. The cancer risk from man-caused radiation is 2
      orders of magnitude lower than that from air pollution with chemical carcinogens.
      Air contamination of classical chemical pollutants presents a major hazard to
      human health.

PMID- 18050703
TI  - [Influence of the environmental hygienic state on the intellectual development of
      Voronezh schoolchildren].
AB  - Voronezh belongs to the areas that have a poor hygienic situation in the
      environmental pollution with heavy metal compounds. The subject of the studies
      was pupils from 2 Voronezh schools situated in the areas hygienically contrast in
      the ambient air and soil pollution with heavy compounds. Their intellectual
      development was studied. A total of 245 pupils from the 2nd, 7th, and 10th forms
      were examined. The best intellectual development indices were recorded among all
      age groups of children living in the hygienically favorable areas. The findings
      are in agreement with the data published by Russian and foreign investigators.

PMID- 18050704
TI  - [Pollutants and their entry into the air of localities].

PMID- 18050705
TI  - [Comparative toxicity of photosensitizers in varying destruction].
AB  - The toxicity of the photosensitizers proflavine acetate (PA) versus methylene
      blue (MB) was evaluated during their varying destruction. Under the influence of
      visible light, a partial (25%) transformation of the photosensitizers was shown
      to be attended by their enhanced toxicity and 100% destruction of the parent
      substances caused a reduction in their hazard. PA and its phototransformation
      products mainly affect the antiperoxide protection system and the structural and
      functional states of the liver, kidney, and duodenum. The maximum noneffective
      dose is 0.002 mg/kg. The possibility of using PA for water disinfection depends
      on the ratio of safe and effective concentrations. A partial (25%) MB destruction
      products cause mutagenic effects; the permissible dose of the mutagen is 0.00025
      mg/kg. MB is not recommended for disinfection of all types of waters.

PMID- 18050707
TI  - [Relationship of the allelic types of xenobiotic detoxification genes to the
      cytogenetic response to a mutagen].

PMID- 18050706
TI  - [Rapid experimental rationale for a waste hazard class by cytotoxicity].
AB  - The paper presents the results of experimental and analytical studies
      substantiating a classification of waste hazard by the cytotoxicity indices. The
      authors have established a significant correlation between the substance toxicity
      values obtained in vivo and in vitro and show it possible to make an approximate
      forecast of the average lethal concentration of substances by the estimates made
      on cell cultures. The criteria for toxicological waste hazard, which are adequate
      to those for the hazards of chemicals by DL50, are given.

PMID- 18050708
TI  - [Use of morphofunctional and cytogenetic studies to analyze the influence of
      environmental factors].
AB  - Long-term studies of 2 (cytohistology and genetic monitoring) laboratories of the
      Research Institute of Human Ecology and Environmental Hygiene, Russian Academy of
      Medical Sciences, to investigate the influence of environmental factors in the
      experiments made it possible to develop a noninvasive procedure for evaluating
      their cytological and cytogenetic impacts on man. A concurrent study of
      morphofunctional (histological, cytological) and cytogenetic parameters in both
      experimental and field trials can substantially extend and refine the
      interpretation of responses to environmental factors, which generates a need for
      using these parameters in hygienic and epidemiological studies.

PMID- 18050709
TI  - [Healthy lifestyle: medical and social approaches].

PMID- 18050710
TI  - [Molecular epidemiology of tick-borne encephalitis].
AB  - The review presents information on the development of studies into the molecular
      epidemiology of tick-borne encephalitis (TBE) in Russia and foreign countries.
      The existence of three major virus genotypes has been established by various
      techniques, such as genomic fragment sequencing, molecular hybridization using
      genotype-specific probes, and restriction fragment length polymorphism test. Each
      of the genotypes prevails in different parts of a natural habitat; the Ural
      Siberian genotype (a Siberian subtype) is most commonly encountered. The genetic
      differences between the strains belonging to different genotypes are great and
      comparable with differences between some mammalian flaviviruses transmitted by
      ticks (viruses of a TBE complex). Further studies of the molecular epidemiology
      of TBE are of importance in understanding the evolution of the causative agent,
      improving the taxonomy and the classification of flavivuruses, and designing
      highly effective methods for the specific diagnosis, prevention, and treatment of
      the disease.

PMID- 18050711
TI  - [Biological and molecular genetic characteristics of a Far-Eastern tick-borne
      encephalitis virus population and its pathogenetic implication].
AB  - The authors have got an idea of the structure of the tick-borne encephalitis
      (TBE) virus population forming in the human body after tick bite in the south of
      the Far East. A hundred and forty-five antigen-positive samples were
      virologically studied in enzyme immunoassays. Human blood leukocytic virus
      isolation on the first day of tick suction testified to the capacity of the virus
      to adsorb and multiply just in the peripheral blood immunocompetent cells. The
      bulk (as high as 70%) of the TBE virus population was non-neuroinvasive strains,
      most of which could rapidly eliminate from man and albino mice. The neuroinvasive
      strains (as high as 30%) caused encephalitis in albino mice and different TBE
      forms (inapparent, feverish, focal). The sequences of 160 bp fragment of
      glycoprotein E gene of 24 strains have shown that they belong to one Far Eastern
      subtype of TVE virus.

PMID- 18050712
TI  - [Development of amplification technology-based methods for tick-borne
      encephalitis virus detection and genotyping].
AB  - The development of methods for tick-borne encephalitis (TBE) virus genotyping,
      such as determination of nucleotide sequences, analysis of restriction fragment
      length polymorphism, polymerase chain reaction using genotype-specific probes
      with hybridization-fluorescence detection, is under consideration. The capacities
      and application area of varions typing techniques, such as TBE detection and
      genotyping in the field, autoptic, and cultural materials; study of circulating
      genotypes in different natural foci and in various viral vectors and carriers,
      are described. Each technique was tested using a large number of strains isolated
      from ill humans and ticks in different regions of the country and employed to
      investigate abundant materials.

PMID- 18050713
TI  - [Experience in implementing the mass immunization program against tick-borne
      encephalitis in the Sverdlovsk Region].
AB  - The urgency of the tick-borne encephalitis (TBE) problem in the Sverdlovsk Region
      is determined by the high rates of morbidity, disability, and mortality in all
      age groups, which is associated with the high activity of a natural focus of TBE.
      A regional mass immunization program against TBE has been developed and put into
      practice to reduce morbidity in the Sverdlovsk Region. Implementation of the
      program requires the administration of all the vaccines registered and permitted
      for use in the Russian Federation. Studies have shown their high epidemiological
      and immunological effectiveness.

PMID- 18050714
TI  - [Current approaches to emergency specific prevention of tick-borne encephalitis].
AB  - Emergency specific prevention of tick-borne encephalitis (TBE) by using
      homologous immunoglobulin is an important element in the package of controlling
      measures against this viral natural and focal infection. There are annually a few
      hundred thousand referrals for health care facilities for tick bites. Their
      maximum coverage tactics via immunoglobulin prevention is medically unreal and
      unjustifiable. The paper presents the results of a long-term application of
      another approach based on preliminary rapid studies of the ticks taken from
      victims or the blood of patients in the period of possible development of
      virusemia and preventive immunoglobulin use only in the persons bitten with TBE
      virus-infected ticks. Examination of the material available from more than 56
      thousand referrals indicated the high epidemiological (more than 99%) and
      economic effectiveness of the target administration of an immunological drug. By
      taking into account the accumulated data on a wide spread of combined foci of TBE
      and other tick-borne infections and the authors' own experience, it is suggested
      that it is necessary to organize a comprehensive differential laboratory
      diagnosis and emergency prevention against the whole complex of Ixodes tick-borne
      infections.

PMID- 18050716
TI  - [Nonspecific prevention of tick-borne encephalitis and other tick-borne
      infections under the present conditions].
AB  - The present situation associated with the use of nonspecific preventive means
      against natural and focal tick-borne infections is analyzed. There is evidence
      that tick populations can be controlled using pesticides. Achieved considerable
      advances in enhancing the efficiency of individual protective means in humans
      against tick attack and suction are reported. It is suggested that these means
      may play a decisive role in the nonspecific prevention of tick-borne infections.

PMID- 18050715
TI  - [Vaccines, immunoglobulins, and test systems for the prevention and diagnosis of
      tick-borne encephalitis].
AB  - The quality of drugs used in the Russian Federation to prevent and diagnose tick
      borne encephalitis (TBE) was analyzed. The TBE vaccines made in Russian were
      shown to be as effective as those manufactured in foreign countries and to have
      the similar production techniques and quality indices therefore they may be
      interchangeable in the population's vaccination. The specific activity of has
      recently increased in terms of the content of TBE virus antibodies. In Russia, a
      wide range of enzyme immunoassay systems have been designed and manufactured for
      the detection of human serum (plasma) IgM and IgG antibodies to TVE virus and for
      that of TBE viral antigen in the biological objects, primarily in the ticks.

PMID- 18050718
TI  - [Main aspects and prospects of medical rehabilitation of urological and
      andrological patients].

PMID- 18050717
TI  - [Molecular genetic characteristics of the strain A/chicken/Moscow/2/2007 (H5N1)
      strain from a epizootic focus of highly pathogenic influenza A among agricultural
      birds in the neear-Moscow region (February 2007)].
AB  - Among agricultural birds in the near-Moscow Region (February 2007), local
      epizootics caused by the highly pathogenic avian influenza A/H5N1 virus seem to
      be of unintended manual origin. Such a situation may be considered to be model
      when the source of inoculation is elucidated in cases of potentially possible
      acts of bioterrorism. Molecular genetic analysis of isolated
      A/chicken/Moscow/2/2007 strain established its genetic similarity with the highly
      pathogenic strains detected in the Black-and-Caspian Sea region in 2006. At the
      same time, comparison of nucleotide sequences of the strain
      A/chicken/Moscow/2/2007 with the strains of Qinghai-Siberian genotype (CSG) for
      which the sequences of full-sized genomes are known in the international
      databases revealed a significant distinction of the near-Moscow strain from the
      earlier known analogues. The uniqueness of the primary structure of the PB1 gene
      is shown. The paper discusses the functional value of amino acid substitutions in
      the proteins of the strain A/chicken/Moscow/2/2007 and in other variants of CSG
      of the subtype H5N1.

PMID- 18050719
TI  - [The state of transmitter systems of the peripheral blood in the norm and in
      patients with exertion angina during laser reflexotherapy].

PMID- 18050720
TI  - [Cardiohemodynamic effects of the ozone therapy in patients with essential
      hypertension].

PMID- 18050721
TI  - [Intermittent hypoxic training in the sanatorium and spa treatment for patients
      with chronic obstructive pulmonary disease].
AB  - The combined examination and treatment in the course of normobaric interval
      hypoxic training of 550 patients with chronic obstructive pulmonary disease was
      performed. Characteristics of change of state of functional respiratory system,
      immunological reactivity, electroencephalography after adaptation to hypoxia in
      the course of interval hypoxic training were determined. Revealed improvement of
      oxygen supply on all stages of its transfer and increase of oxygen consumption in
      tissues resulted in normalization of electrobiological activity of cerebral
      cortex, correction of immunological reactivity. High efficiency of interval
      hypoxic training in the combined treatment for patients with chronic obstructive
      pulmonary disease was proved.

PMID- 18050722
TI  - [Infitatherapy of children with bronchial asthma].
AB  - Use of nonmedicamental methods of treatment assists to improve the control of
      children's bronchial asthma clinical course. Pulsed low-frequency electromagnetic
      field regulates the state of central and vegetative nervous system and improves
      psychological status of child. Inphytotherapy has bronchial spasmolytic and
      immune correction effects.

PMID- 18050723
TI  - [Postoperative rehabilitation of patients with dyshormonal hyperplasia of the
      prostate].

PMID- 18050724
TI  - [Successive postoperative rehabilitation of patients after reconstructive plastic
      surgery in the connection with tube-peritoneal sterility].

PMID- 18050725
TI  - [Biorhythms to improve efficiency of the treatment of patients with chronic
      opisthorchosis].
AB  - To make the treatment of bile-excreting dysfunctions more effective still remains
      an actual problem of clinical medicine. Use of chronobiological approach in the
      treatment is possible to resolve that problem. For any system including bile
      excreting one, its own biorhythms are typical. Lesion of these systems causes
      changes of the biorhythms. Use of parameters of biorhythms of bile-excreting
      system activity expects an individual or group chronobiological approach in the
      treatment of patients with chronic opisthorchosis. The combined treatment of
      opisthorchosis with the use of such approach makes possible to improve efficiency
      of the treatment and to maintain received effect up to 6 months. It indicates
      increase the terms of remission and prevents development of early recidivation.

PMID- 18050726
TI  - [Changes in cerebral hemodynamics in patients with posterior cervical sympathetic
      syndrome under the manual therapy in combination with alternating magnetic
      field].

PMID- 18050727
TI  - [Training in a diabetes school and physiotherapy in the treatment of patients
      with type II diabetes mellitus].

PMID- 18050729
TI  - [All Russian Forum "Zdravnitsa-2007". Ufa, Bashkortostan Republic, May 15-18,
      2007].

PMID- 18050730
TI  - [Advances in the study of expression and regulation of P-glycoprotein].
AB  - Resistance to the cytotoxic actions of antineoplastic drugs remains a barrier to
      the establishment of curative chemotherapy regimens for cancer. Over-expression
      of P-glycoprotein (P-gp), encoded by the MDR1 gene is the major molecular
      mechanism enhancing efflux pump for various anticancer agents, hence caused MDR.
      Transcription factor, DNA methylation, histone acetylation/deacetylation,
      phosphorylation and glycosylation and MDR1 gene polymorphisms play pivotal role
      in regulation of P-glycoprotein, and may become new therapeutic targets. This
      paper summarized the advances of studies on expression and regulation of P
      glycoprotein.

PMID- 18050731
TI  - [Advances in the study of ginsenoside compound K].
AB  - Ginsenoside compound K is the main metabolite of protopanaxadiol type ginseng
      saponins in intestine after oral administration and also is the major form of
      protopanaxadiol saponins absorbed to the body. Recently, ginsenoside compound K
      has received increasing attention, because in vivo or in vitro various biological
      actions of anticancer, hepatoprotective and anti-inflammatory etc, have shown to
      be mediated by this metabolite. In this paper, the studies of preparation,
      bioactivities, absorption, distribution and pharmacokinetics of compound K were
      reviewed in detail.

PMID- 18050732
TI  - [Recent advances in the study of dendrimers-based drug delivery systems].
AB  - Dendrimers are hyperbranched, monodisperse and three dimensional macromolecules,
      which consist of an apolar core and polar shell have been referred to as
      "unimolecular micelles". This paper briefly describes the development and
      structural characteristics of dendrimers and also explains the feature of
      dendrimers as drug carrier and the dendrimer-drug interactions in details.
      Recently, dendrimers, which have attracted increasing attention for their
      applications in many fields such as drug targeted delivery systems and gene
      transfection, are becoming potential novel carriers.

PMID- 18050733
TI  - Effects of Ginkgo biloba extract on expressions of IL-1beta, TNF-alpha, and IL-10
      in U937 foam cells.
AB  - This study is to investigate the protein and mRNA expressions of pro-inflammatory
      and anti-inflammatory cytokines in U937 foam cells and effects of Ginkgo biloba
      extract (GbE) on the cytokines. U937 cells were cultured with different
      concentrations of GbE (0.1, 1, and 10 microg x L(-1)), and stimulated by 100 mg x
      L(-1) oxidized low density lipoprotein (ox-LDL) for 24 h. The expressions of
      interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-10 (IL-10) in culture solution were detected by enzyme-linked
      immunosorbant assay (ELISA) and reverse transcriptase polymerase chain reaction
      (RT-PCR). The results showed that incubated with 100 mg x L(-1) ox-LDL for 24 h,
      the U937 cells became foam cells, the protein or mRNA expressions of IL-1beta,
      TNF-alpha, IL-10, and its receptor IL-10R in U937 foam cells were higher markedly
      than those in normal U937 cells. When the cells were pretreated with GbE (0.1, 1,
      and 10 microg x L(-1)), the increases of IL-1beta and TNF-alpha in U937 foam
      cells were remarkably inhibited, but IL-10 expression increased greatly.
      Especially when cells were pretreated with 10 microg x L(-1) GbE, the protein and
      mRNA expressions of IL-1beta and TNF-alpha were markedly lower than those in U937
      foam cells. The protein expression of IL-10 and mRNA expressions of IL-10 and its
      receptor IL-10R were markedly higher than those in U937 foam cells. GbE inhibited
      production of pro-inflammatory cytokines IL-1beta and TNF-alpha, but up-regulated
      the production of anti-inflammatory cytokine IL-10 and its receptor IL-10R in
      U937 foam cells, which might be related with its anti-atherosclerotic actions.

PMID- 18050734
TI  - [Protective effect of (-) clausenamide against neurotoxicity induced by okadaic
      acid and beta-amyloid peptide25-35].
AB  - This study is to investigate the protective effect of (-) clausenamide against
      the neurotoxicity of okadaic acid in SH-SY5Y cell line, and injection beta
      amyloid peptide25-35 (Abeta25-35) to the cerebral ventricle in ovariectomy (OVX)
      rats. MTT assay, LDH assay, and Hoechst 33258 staining were used to detect the
      effect of (-) clausenamide on the toxicity of okadaic acid in SH-SY5Y cell line.
      The animal model was induced by ovariectomized and injection of Abeta25-35 in the
      cerebroventricle of rats. The effect of (-) clausenamide on learning and memory
      deficiency was observed by step-through test. Electron microscope, Nissl body
      staining, and HE staining were used to examine the morphological changes in
      hippocampus and cerebral cortex neurons. Pretreatment of (-) clausenamide and
      LiCl decreased the rate of cell death from MTT, LDH release, and apoptosis from
      Hoechst 33258 staining in SH-SY5Y cell line. The step-through tests showed (-)
      clausenamide could improve the ability of learning and memory. The Nissl body
      staining and HE staining experiments also showed the neuroprotective effects of (
      ) clausenamide on the neurons of hippocampus and cerebral cortex. (-)
      Clausenamide has the protective effects against the neurotoxicity induced by
      okadaic acid and Abeta25-35.

PMID- 18050735
TI  - [Expression and bioactivity of the cloned staphylococcal enterotoxin O].
AB  - This study is to clone the gene of staphylococcal enterotoxins O, obtain
      recombinant protein (rSEO) and investigate its activity on mice lymphocyte.
      Staphylococcus aureus O gene is cloned into GST gene fusion vector pGEX-4T-1. The
      resultant plasmid pGEX-4T-SEO was used to transform E. coLi BL21, where the GST
      SEO fusion protein was expressed efficiently. Then SEO was purified by
      Glutathione Sepharose 4B affinity column and digested with thrombin. The
      bioactivity of SEO was analyzed by MTT assay on mice lymphocyte and tumor cells.
      The nucleotide sequence was confirmed to code for the protein correctly, and
      soluble SEO was expressed efficiently in E. coli BL21 with pGEX-4T-SEO. The
      protein purified by affinity chromatography resulted to be one single band by SDS
      PAGE detection. The MTT assay of the purified rSEO demonstrated that its
      abilities of stimulating T cells and inhibiting the proliferation of K562, K562
      ADM and B16 cells were equivalent to that of SEC in vitro. The expression plasmid
      pGEX-4T-SEO was constructed and the recombinant superantigen was expressed
      successfully, which may provide a foundation for the further research of the
      anticancer activity of SEO.

PMID- 18050736
TI  - [Reversal effect and mechanism of arsenic trioxide on multidrug resistance of
      gastric carcinoma cells SGC7901].
AB  - The purpose of this study is to investigate the reversal effect and its mechanism
      of arsenic trioxide (As2O3) on multidrug resistance of gastric carcinoma cells.
      The concentration of vincristine (VCR) increased gradually to induce the drug
      resistance of gastric carcinoma cell SGC7901. MTT assay was used to determine the
      lethal effect of anticarcinogens on tumor cells and Western blotting assay was
      applied to determine the expression of P-glucoprotein (P-gp) and glutathione S
      transferase (GST-s) in tumor cells. As a result, the resistance of SGC7901/VCR
      cells to VCR, fluorouracil and epirubicin was 16.56, 2.69 and 13.05 times,
      respectively, more than that of SGC7901 cells. After 24 h precondition with
      As2O3, RI of vincristine, fluorouracil and epirubicin decreased significantly (P
      < 0.05). Expression of P-gp and GST-s in resting SGC7901/VCR cells was
      significantly higher than that in carcinogen-sensitive SGC7901 cells. As2O3
      decreased the expression of P-gp and GST-s in SGC7901/VCR cells significantly,
      while it showed no significant effect on carcinogen-sensitive SGC7901 cells. The
      result suggested that As2O3 could partly reverse drug resistance of SGC7901/VCR
      cells by probably the mechanism of decreasing the expression of P-gp and GST-s.

PMID- 18050737
TI  - [Protective effect against monoammonium glycyrrhizinate on lipopolysaccharide
      induced acute lung injury in mice].
AB  - The aim of this study is to investigate the effect of monoammonium
      glycyrrhizinate (MAG) on lipopolysaccharide (LPS) -induced acute lung injury
      (ALI) and its anti-inflammatory mechanism in mice. All male ICR mice were
      randomly divided into six groups: LPS group; control group; MAG 3, 10, and 30 mg
      x kg(-1) groups; and dexamethasone (DXM) 5 mg x kg(-1) group. Lung dry weight and
      wet weight percentage and permeability were detected. Neutrophil infiltration in
      bronchoalveolar lavage fluid (BALF) and lung tissues was detected by cell count
      and morphological analysis. The levels of TNF-alpha and IL-10 in lung were
      detected by ELISA. MPO activity was determined followed the specification. MAG
      induced a decrease in lung wet weight/dry weight ratio, and significantly
      decreased in total leucocyte number and neutrophil percentage in the BALF, and
      MPO activity of lung in a dose-dependent manner. Importantly, It could up
      regulate the IL-10 level and down-regulate the TNF-alpha level in the lung tissue
      of ALI mice. These results suggested that the protective effect of MAG in mice on
      LPS induced ALI was associated with the regulation of TNF-alpha/IL-10 balance,
      and MAG maybe a potentially treatment for ALI/ARDS.

PMID- 18050738
TI  - Two novel compounds from Ardisia punctata Lindl.
AB  - To study the chemical constituents of Ardisia punctata, compounds were isolated
      with a combination of multi-chromatography. Their structures were determined on
      the basis of spectral analysis and comparison to those of the known compounds. A
      1,4-benzoquinone derivative and a alkylphenol were isolated from the petroleum
      ether extract of the roots of Ardisia punctata. Their structures were elucidated
      as 2-tridecyl-3-[(2-tridecyl-4-acetoxy-6-methoxy)-phenoxyl] -6-methoxy-1,4
      benzoquinone (1) and 2-methoxy-4-hydroxy-6-tridecyl-phenyl acetate (2). The two
      compounds are both new.

PMID- 18050739
TI  - [A new chemical component of Pueraria lobata (Willd.) Ohwi].
AB  - Pueraria lobata (Willd.) Ohwi. was extracted for two times with 70% ethanol and
      the 70% ethanol-extracts was condensed. Various column chromatography with AB-8
      macroreticular resin, Toyopearl HW-40, pharmadex LH-20, and silica gel were
      employed for the isolation and purification of the 70% ethanol-extracts from
      Pueraria lobata (Willd.) Ohwi. Five compounds were isolated and their structures
      were identified by physiochemical properties and spectral analysis (UV, IR, MS,
      1H NMR, 13C NMR, HMQC, HMBC, etc.): (4R)-3-[ 2-hydroxy-4-methoxyphenyl]-4-(4-beta
      D-glucopyranosyloxybenzyl) but-2-en-4-olide (1), 4', 8-dimethoxyl-7-O-beta-D
      glucopyranosyl isoflavone (2), eicosanoic acid (3), hexadecanoic acid (4),
      tetracosanoid acid-2,3-dihydroxypropyl ester (5). Compound 1 was a new compound,
      and compounds 2, 3, 4 were isolated from this plant for the first time.

PMID- 18050740
TI  - [Fingerprint of volatile oil of Atractylodes lancea by GC-MS].
AB  - To study the fingerprint of the volatile oil of Atractylodes lancea (Thunb.) DC.,
      and to offer the characteristic data for the quality evaluation, GC-MS analysis
      was performed for 17 samples of different areas used as Atractylodes lancea
      (Thunb.) DC. Nine kinds of same components were selected. TIC profiles were
      evaluated by "Computer Aided Similarity Calculation". The characteristic peaks in
      chromatograms were identified by comparing mass data with literatures.
      Hierarchical clustering analysis was performed by SPSS based on the relative peak
      area (RPA) of identified peak to atractydin in 17 samples. The mutual mode
      fingerprint plots of genuine Atractylodes lancea (Thunb.) DC. have been
      established, the matching of active components was characteristic that
      atractylon, hinesol, beta-eudesmol, atractydin as (0.89 - 1.12): (0.11 - 0.15) :
      (0.48 - 0.61) : 1. The difference of resemblance of not genuine samples with
      genuine samples was remarkable. Two categorizations were clustered. Atractylodes
      lancea (Thunb.) DC. from genuine and Tangshan and Nanshan, Jiangsu Prov. were in
      a group, while those from Anhui and Hubei Prov. were in another group. The
      characteristic fingerprint of genuine Atractylodes lancea (Thunb.) DC. combined
      with the study of the matching of active components for the quality control and
      the resemblance calculation of fingerprints and SPSS hierarchical clustering
      analysis provided a new analytic method for the quality evaluation and
      discrimination of Atractylodes lancea (Thunb.) DC.

PMID- 18050741
TI  - [Determination of curcumol in plasma by HPLC-MS/MS method and its
      pharmacokinetics in Beagle dogs].
AB  - To establish a high performance liquid chromatography (HPLC) coupled with tandem
      mass spectrometry quantitative detection method for the determination of
      curcumol, the main ingredient of zedoary turmeric oil fat emulsion, and
      investigate its pharmacokinetics in Beagle dogs, nine healthy Beagle dogs were
      divided into three groups, and blood samples were collected at scheduled time
      points after intravenous injection of 7.5, 10 and 12.5 mg x kg(-1) zedoary
      turmeric oil fat emulsion. The concentrations of curcumol were determined and
      pharmacokinetics was calculated. A good linearity was obtained from 0.25 to 100
      ng x mL(-1) in plasma. The relative recoveries were from 91.33% to 103.17%, and
      the absolute recoveries were from 31.61% to 37.20%. The intra-day and inter-day
      variances (RSD) were < 15%. The main pharmacokinetic parameters of curcumol after
      intravenous injection of 7.5, 10 and 12.5 mg x kg(-1) zedoary turmeric oil fat
      emulsion were as follows, T1/2 : (2.0 +/- 0.4), (1.7 +/- 0.2) and (2.3 +/- 0.8)
      h, AUC(0-infinity): (15.1 +/- 2.7), (18.3 +/- 2.0) and (29.5 +/- 4.0) ng x mL(-1)
      x h; MRT: (0.9 +/- 0.1), (0.8 +/- 0.2) and (0.8 +/- 0.1) h, CL: (21.9 +/- 4.0),
      (24.9 +/- 6.0) and (18.4 +/- 1.2) L x h(-1) x kg; Vd : (65.4 +/- 26.5), (62.0 +/-
      13.4) and (61.2 +/- 19.8) L x kg(-1), respectively. The developed method was
      rapid, highly sensitive and specific and could be used in curcumol
      pharmacokinetic studies in vivo. A three-compartment model was best fit to the
      plasma concentration--time curves obtained in Beagle dogs and the plasma AUC was
      increased proportionally with doses.

PMID- 18050742
TI  - [Determination of artemisinin, arteannuin B and artemisinic acid in Herba
      Artemisiae Annuae by HPLC-UV-ELSD].
AB  - To establish an HPLC-UV-ELSD method for the determination of the content of
      artemisinin, arteannuin B and artemisinic acid in Herba Artemisiae Annuae. The
      analytical column was Nucleodur RP-C18 (250 mm x 4.6 mm, 5 microm ID). The mobile
      phase was acetonirile-0.1% acetic acid (50: 50) and the flow rate was 1.0 mL x
      min(-1) with a UV detector for artemisinin, the detection wavelength at 209 nm,
      and the evaporative light-scattering detector (ELSD) for arteannuin B and
      artemisinic acid, the drift tube temperature: 50 degrees C, the nitrogen flow
      rate 30 psi and the gain was 50. The resolution of artemisinin, arteannuin B and
      artemisinic acid was good. The linear calibration curves were obtained over the
      range of 0.52 - 2.6 microg for artemisinin (r = 0.999 4, n = 5), 0.022 - 4.4
      microg for artemisinin B (r = 0.999 9, n = 5) and 0.203 - 8.12 microg for
      artemisinic acid (r = 0.999 8, n = 5), separately. The mean recoveries of the
      three compounds were 99.45%, 102.37% and 101.10% with RSD of 2.3%, 1.7% and
      0.79%, respectively. This method is simple, rapid, accurate and suitable for the
      determination of the content of the three compounds in the herbs.

PMID- 18050743
TI  - [Cationic liposomes loaded with doxorubicin targeting to the tumor neovasculature
      in vitro].
AB  - This study was conducted to investigate the in vitro characteristics of cationic
      liposomes composed of 3beta-[N-[2-(N', N'-dimethylamino) ethyl] carbamoyl]
      cholesterol (DC-Chol) and dipalmitoylphosphatidylcholine loaded with doxorubicin
      (DXR), and to provide useful information for the in vivo tumor vascular targeting
      of cationic liposomes. Cationic liposomes composed of different amounts of DC
      Chol (0 mol%, 10 mol%, 25 mol%, 50 mol%) were loaded with the conventional anti
      cancer drug doxorubicin. Their size, zeta potential, encapsulation efficiency,
      and DXR release in vitro were investigated. Moreover, their uptake by rat aortic
      endothelial cells (RAECs) was observed at 15 min, 30 min, 1 h, and 4 h of
      incubation. FITC-Dextran was i.v. injected to the H22 tumor-bearing KM mice to
      stain the neovasculature. The characteristics of resulting DXR-loaded cationic
      liposomes were in stable characteristics with particle sizes around 100 - 200 nm
      and capsulation efficiency greater than 90%. Increased cationic lipid led to
      enhanced zeta potential, and meanwhile it also resulted in quick release of the
      loaded drug, indicating increased slits or pores on the membrane upon the
      addition of DC-Chol. RAECs could more avidly take up DXR-loaded cationic
      liposomes when the content of DC-Chol increased in the liposomes, and DXR were
      quickly released in the cytoplasm and transported to the nuclei. The
      neovasculature stained by FITC-Dextran was clearly observed. DXR-cationic
      liposomes composed of DC-Chol could be used for tumor vascular targeting in vivo
      for further study.

PMID- 18050744
TI  - [The inhibitory effect of pluronic on P-glycoprotein drug pump].
AB  - To investigate the inhibitory effect of Pluronic on P-glycoprotein (P-gp) drug
      efflux pump, Caco-2 cells and animal models were established to study the
      influence of Pluronic on celiprolol transport across Caco-2 cell monolayer and
      intestinal mucous membrane with verapamil set as a positive control. Drug
      concentration was measured by HPLC and the apparent permeability coefficient
      (P(app)), absorption rate constant (k(a)) and the effective permeability
      coefficient (P(eff)) were calculated. P(app) of basolateral to apical side and
      apical to basolateral side was (2.10 +/- 0.13) x 10(-6) and (0.333 +/- 0.018) x
      10(-6) cm x s(-1), respectively. Transports of celiprolol across Caco-2 cell
      monolayer were influenced by both verapamil and Pluronic. The absorption
      constants (k(a)) of celiprolol at duodenum, jejunum, ileum, and colon were (0.09
      +/- 0.03), (0.14 +/- 0.04), (0.11 +/- 0.03) and (0.05 +/- 0.02) h(-1), k(a) of
      celiprolol in verapamil group were (0.14 +/- 0.03), (0.24 +/- 0.02), (0.25 +/-
      0.03) and (0.23 +/- 0.02) h(-1), and k(a) of celiprolol in Pluronic group were
      (0.13 +/- 0.02), (0.22 +/- 0.02), (0.22 +/- 0.03) and (0.20 +/- 0.03) h(-1),
      respectively. Pluronic showed significant effect on inhibiting P-gp of Caco-2
      cell and intestinal mucosa in rats.

PMID- 18050745
TI  - [Increasing the content of active constituents in Polygonum cuspidatum hairy root
      by gene transformation technology].
AB  - To increase the content of active constituent--RE and PD of Polygonum cuspidatum
      hairy root, through Ri-mediated gene transformation technology, modified high
      salt low pH method was used to distill genome DNA of grapevine (Vitis raparia).
      Primer was designed according to sequence of Genebank (AF128861). Through PCR
      amplification obtain RS gene sequence was obtained. Binary vector pCAMBIA1300-35S
      RS was constructed. Frost thawing method was used to transform Agrobacterium
      rhizogenes ATCC11325. Scratched aseptic seedling leaf of Polygonum cuspidatum was
      contaminated subsequently. DNA conformity and mRNA expression of RS gene were
      investigated by PCR and RT-PCR respectively. RE and PD in transgenic hairy root
      were determined by HPLC. For the first time successfully inducement acquires
      transformed RS gene hairy root of Polygonum cuspidatum. Content of active
      constituents--RE and PD were 17 - 187 microg x g(-1) DW and 836 - 1 970 microg x
      g(-1) DW, respectively, the non-transgenic hairy root was 0 - 130 microg x g(-1)
      DW and 190 - 320 microg x g(-1) DW. In the different root selected, the content
      of PD was much higher than that in non-transformed hairy roots of Polygonum
      cuspidatum, the highest content is 5 times, but the content of RE has not
      increased apparently.

PMID- 18050746
TI  - [Optimization of expression condition of SARS-CoV PUPs genes in E. coli].
AB  - According to previous studies of SARS-CoV (Severe acute respiratory syndrome
      coronavirus), a variety of novel accessory genes have been identified in SARS-CoV
      genome, which were interspersed the structural genes of SARS-CoV and considered
      to be unique to the SARS-CoV genome. The predicted unknown proteins (PUPs)
      encoded by the accessory genes might play important roles in the SARS-CoV
      infection. Three of those genes, called X4, X5 and ORF10, were synthesized and
      introduced into E. coli to induce expression. SDS-PAGE and Western blotting
      revealed that the three genes have been expressed in E. coli. The induction of
      SARS PUPs genes expression in different temperatures, induction times, IPTG
      concentrations and A values of E. coli cells were performed. The optimal
      induction condition of SARS-CoV PUPs genes was characterized according to the
      orthorgonal analysis. The ratio of recombinant proteins of PUPs to total proteins
      is as follows: X4, 20%; X5, 27.8%; ORF10, 68.5% under the optimum conditions.

PMID- 18050747
TI  - ANA BACKGROUNDERS: influenza season 2007-2008.

PMID- 18050748
TI  - Patients generally love nurses because nurses help them and advocate for them.

PMID- 18050749
TI  - [Introduction to the development and evolution of Spanish Urology].

PMID- 18050750
TI  - [The meaning of erection, genitality, and other representations of urologic
      topics in the paleolithic imaginary].
AB  - The history of urology starts with written documents making express reference to
      procedures, practices and descriptions of morbid processes related with the male
      genitourinary tract. Oddly, the most recent prehistoric period, the superior
      Paleolithic (from approximately 40.000 years to 12.000 years ago; the longest
      period since our species entered the history of humanity) also has graphic
      documents expressing how the human being understood the physiologic phenomena and
      how he observed the pathologic processes of this organism. The representations
      with genitality expressions enable us to understand the meaning of erection from
      the Paleolithic perspective, and even the possible existence of a culture based
      on preputial retraction or rituals of circumcision. Several urologic disorders
      such us phimosis, paraphimosis, discharge, priapism, and even scrotal mass appear
      represented at that time and constitute the first sign of knowledge of what can
      be called primitive urologic knowledge.

PMID- 18050751
TI  - [Urological diseases in the works of Abulcasis].
AB  - OBJECTIVES: To perform a study on the surgical work of Abulcasis in the field of
      urology, to know the surgical tools and different techniques used, as well as the
      innovations applied to solve some features of urological diseases. METHODS: The
      part on urology from the book XXX by Tasrif, the edition from Strasbourg in 1532
      was reviewed and translated from Latin. RESULTS: The author does not refer much
      to the clinical features of the various pathologies of the genitourinary
      apparatus; he focuses instead on the surgical treatment of them. The author
      usually used the "cautery" mainly to control hemorrhage in various operations.
      Some of these surgical practices are being used nowadays. CONCLUSIONS: Abulcasis
      was the first doctor born in Spain that studied the surgical treatment of
      urological diseases and performed a graphic study on the tools used. He
      introduced technical innovations on different operations and described for the
      first time the vesical lithotomy on women, and vesical and urethral lithotripsy.

PMID- 18050752
TI  - [Male aging in the Middle Ages: commentaries on the book by Arnau de Vilanova
      "Conservatio juventute preservatio senectute"].
AB  - In the Middle Ages medical texts the notes about personal hygiene are scarce and
      they are dedicated to the Kings or the aristocracy. In his work Regimen sanitatis
      ad inclytum regen Aragorum, Amaldo de Vilanova underlines six things that are
      necessary for cleanliness, among which he includes his well-known proposition
      Conservatio juventute preservatio senectute. We compared his text with those from
      other authors with references to the issue and, once examined, Vilanova's work
      stands out. Doctors in the middle ages were already interested in aging and
      propositions considered today as modern are found described in various works from
      that period.

PMID- 18050753
TI  - [The intervention of Dr Francisco Diaz in the inquisitorial process against
      Elena/o de Cespedes, a transsexual surgeon found guilty by the Inquistion in
      Toledo in 1587].
AB  - OBJECTIVES: To make known, comprehensively, an almost unknown episode in the life
      of Dr. Francisco Diaz (1527-1590), surgeon of the king Philip II, and author of
      the first urology treaty in the history of medicine. To our knowledge, to date
      there were few references about the participation that, as an expert, Francisco
      Diaz had to have in the inquisitorial process against Elena de Cespedes, a
      presumed hermaphrodite accused by the Inquisition because being a woman married
      another one pretending to be a man. The trial was carried out in Toledo in 1587
      and had great impact in that time, because the accused, dressing with male
      clothes and usurping the prerogatives of a man, had gotten by fraud titles and
      favours which were forbidden for women, the title of surgeon among them. Except
      for the reference by Folch Jou and Burshatin, both short and incomplete, no other
      author or biographer of the famous surgeon had cited this episode of his life,
      which to our judgment could mean a great damage to his reputation. METHODS: We
      reviewed the works by the two aforementioned authors, all the works and
      biographies about Dr. Francisco Diaz that we could found, and microfilmed and
      transcript the whole bundle 234, expedient 24, from the section Inquisition at
      the National Historical Archive in Madrid, corresponding to Elena de Cespedes
      (alias Eleno) (> 500 pages) to obtain the greatest amount of data about the
      accused and the performance of Dr. Francisco Diaz. RESULTS AND CONCLUSIONS:
      Francisco Diaz was requested, as an expert, by the Vicar of Madrid to perform the
      examination of the genitourinary organs to give or not marriage license to that
      woman saying she was a man. In his report in the year 1586, surprisingly the
      urologist declared that the petitioner was a man. As it would be demonstrated
      during the trial, the accused, who alleged being hermaphrodite in her defense,
      had been able to deceive the expert with her tricks altering her genital
      morphology. Thanks to her surgical knowledge she had mutilated herself surgically
      closing her vagina and placed a device to simulate she was a male. At the end,
      after the opinion of the counter experts of the Inquisition Francisco Diaz had to
      retract, confirmed that the accused was a female, and accused her of witchcraft
      to save his responsibility. Nevertheless, in the work we conclude that the
      accused was a male transsexual, which, in part, would excuse the urologist's
      error 400 years later.

PMID- 18050754
TI  - [Pedro Martin Martinez, professor of anatomy at the General Hospital of Madrid].
AB  - OBJECTIVES: The study of the anatomical works written by Martin Martinez and his
      relationship with urology. Also, the appreciation of his open scientific
      mentality and scepticism in a historic environment imbued of a scholastic spirit
      and dogmatism. METHODS: Several Martin Martinez's works were reviewed, mainly the
      treaty Complete human anatomy, entire text obtained from the electronic page of
      the Complutense University library, and also the words from other authors of his
      time. RESULTS: The medical and philosophical personality of Martin Martinez and
      his influence in the medical knowledge in the Spanish Court during the first
      quarter of the 18th century are ascertained. The importance he had as Professor
      of anatomy in the functioning and development of the Madrid's Anatomical
      Amphitheater in the General Hospital and his positive repercussion on the
      training of students and surgeons of that time and posterior years is
      appreciated. Writing his works in Spanish contributed to it. CONCLUSIONS:
      Although he cannot be considered an outstanding scientific personality in
      comparison with authors from other European countries, he must be recognized for
      his great merit with his open mind and his labour against dogmatism in front of
      the blocked-in-servility medical mentality, and also in the study of classic
      authors from previous centuries.

PMID- 18050755
TI  - [Urology before illustration. From the Urology of the Royal College of Cadiz to
      that of the "veneranda" gathering].
AB  - The study of the urological activity in the Andalusian occident is contained in
      the printed and handwritten "Observations" of the records of the Royal Society of
      Medicine of Seville and the Royal College of Surgery of Cadiz. They encompass the
      period from 1693 to the first third of the 18th century. By the first of October
      1701, the "Veneranda" gathering consolidates and Philip V gives the "royal
      warrant". The "Royal Society of Medicine and Other Sciences of Seville" starts
      its medical-surgical path. It should be reminded that all the Andalusian surgery
      and specially the one from Cadiz (through the Royal College of Surgeons) was
      present in the Royal Society. Ordonez de la Barrera, Sanchez Bernal, Fray
      Ambrosio de Guibeville, Juan Lacombe, Pedro Virgili and many others were founders
      of this extraordinary event. Surgical training and, by extension, urological
      training had their root and basement in the anatomical amphitheaters (Seville
      1731 and Cadiz 1728), which were considered ungodly by the Church. Jose Celestino
      Mutis (1750-53) and Pedro Fernandez Castilla (1741) excluded the university from
      this new movement. There was and intense relationship between Navy surgeons and
      the Royal Society, being members since its foundation: Guibeville (1719); Sanchez
      Bernal (1719); Gregorio Arias (1729); Gaspar de Pellicer (1729); Lacombe (1730);
      Fernandez Castilla (1741); Calero (1789). The main protagonist was Luis Montero,
      real paradigm with projection to the next century, having a neat French influence
      altogether with Ramos, both of them being Beaumond's alumni (an anatomist of
      recognized prestige).

PMID- 18050756
TI  - [Knowledge of the urogenital diseases in the work of Gaspar Casal, "natural and
      medical history of the Principality of Asturias" (1762)].
AB  - OBJECTIVES: Gaspar Casal (Gerona, 1680, Madrid, 1759) made most of his medical
      work in Oviedo (Asturias, Spain), where he lived for thirty-four years, before
      his return to Madrid as a doctor for the Royal House. Fruits of this work is the
      book "Natural and medical history of the Principality of Asturias" (Madrid,
      1762), considered the best exponent of the Spanish medicine of the 18th century,
      and where the "disease of the rose", known later as pellagra or hypovitaminosis
      B, was first described in. METHODS: Study of the life of Gaspar Casal and
      analysis of "Natural and medical history of the Principality of Asturias",
      speculating on the knowledge about nephro-urologic and external genitalia
      diseases that can be deduced from the text. RESULTS: Casal knows and treats
      kidney lithiasis, relating it either to joint diseases and gout, or to dietetic
      excess and sedentary life in some of his patients. Other diseases coursing with
      poliuria and oedemas, are compatible with the nowadays diagnosis of infectious or
      degenerative nephritis. He rarely uses a bladder catheter for cases of stranguria
      and anuria, probably including some patients with anuria and others with urinary
      retention in the term "renal ischuria or high suppression", although he also uses
      the term "vesical ischuria" for the last ones. He treats the symptoms disuria
      stranguria and haematuria, with empiric therapy, and, as it may be deduced from
      the text, some local surgeons didn't use or know to alleviate those symptoms with
      urethral catheterisation. He attends an epidemics of mumps, with orchitis in male
      patients, that were treated with bloodletting, although he stood against the
      misuse of phlebotomy in several diseases. Only occasionally he orders surgical
      treatment for several testis diseases. CONCLUSIONS: "Natural and medical history
      of the Principality of Asturias" reflects the spectrum of diseases that conforms
      the day-to-day working schedule of a Spanish family doctor in the beginning of
      the 18th century, that is to say: diseases resulting from dietary shortage,
      infective, parasite, degenerative and vascular-cerebral diseases in older
      patients. From the nephro-urologic point of view, it is very interesting to read
      about the knowledge on stone diseases and lower urinary tract symptoms, that were
      treated as recommended by the classic authors, with physical therapy and empiric
      formulas, rarely with bladder catheterization. To a lesser degree, the results of
      the medical treatment of orchitis and the surgical treatment of some testis
      diseases are also depicted.

PMID- 18050757
TI  - [Goya and his lower urinary tract symptoms in Bordeaux, 1825].
AB  - The famous painter Francisco de Goya y Lucientes (1746-1828) suffered during his
      life one or several diseases, the nature of which has not been determined with
      certainty. The partially documented morbid episodes that happened during the
      years 1792-1793 in Seville and Cadiz, 1819 in Madrid, and 1825 in Bordeaux could
      be related. In the latter one, the urological signs and symptoms the
      distinguished patient presented have been demonstrated. The objective of this
      paper is to propose the hypothesis of neurosyphilis' dorsal tabes responsible for
      the voiding disorders he presented in Bordeaux in the spring of 1825, having as a
      resource Goya's "diplomatario", with the letters and documents that have been
      collected and made known to date, with the purpose of using an inductive
      deductive method for their study and interpretation, setting an interrelation
      between these valuable sources with both the medical knowledge of the period and
      the current, particularly in urological features, and reviewing the available
      bibliography on that topic, with the natural reserve about giving a retrospective
      diagnosis which cannot be completely true due to its inherent characteristics. In
      the same way, and as a complement, we include a brief review of some
      circumstances and characters that surrounded the artist in France to help to
      incardinate and better understand the personality of Goya, already old and sick
      at that time.

PMID- 18050758
TI  - [Federico Rubio y Gali, "Prince of Surgery", and the Urology in Seville in the
      19th century].
AB  - The present work describes the figure of Dr. Federico Rubio y Gali, pioneer and
      promoter of Spanish Medicine during the 19th century, as well as the repercussion
      of his scientific talent in the development of modern urology. It is also
      mentioned the creation of the Free School of Medicine and Surgery of Seville, as
      concretion of his educational vocation and contribution to the teaching of
      urological knowledge.

PMID- 18050759
TI  - [The start of urological teaching in the Spanish University. Dr. Alberto Suarez
      de Mendoza].
AB  - OBJECTIVES: We present a biographical sketch of Dr. Suarez de Mendoza, one of the
      first urologists trained as so in the Necker Hospital in Paris with Dr. Guyon,
      who opened the field to the creation of this speciality in Spain, and first
      official professor of the subject of in the Faculty of Medicine of Madrid.
      METHODS: We reviewed his academic expedient in the National Historical Archive
      and search for data about his presence in Spain in the Faculty of Medicine and
      Medical College of Madrid. From the Royal Decrees we obtained information about
      the Free School of Medicine, and the creation of medical specialities in the
      University study plans; finally, we analyzed his written works.
      RESULTS/CONCLUSIONS: We consider Dr. Suarez de Mendoza one of the personalities
      giving entity to Urology in our country, for his education, for the amplitude of
      his knowledge, and for his wide experience, as professor of the subject in the
      Spanish University, as author of a great number of published works, and as
      inventor of his contributions to the development of anesthesia and urology. His
      treaty the first in Spanish covering in detail the innovations in urological
      examination methods, enables us to know and value the progressive advance and
      evolution of knowledge in urology.

PMID- 18050760
TI  - [The teaching of Dr. Francisco Romero Aguirre].
AB  - OBJECTIVES: After the death of Professor Francisco Romero Aguirre (Zaragoza
      6/7/1918-6/28/2006) we want to make known his great teaching vocation, so that we
      covered his link with University from the start of his studies to his
      professorship as first professor in urology in the Spanish University (1961), and
      his work at the chairmanship of the Professional Postgraduate School of Urology
      in the University of Zaragoza. METHODS: We reviewed his biography, his edited
      works and publications of the Urology Chair at the University of Zaragoza, and
      obtained as many references as we found about his teaching activity. RESULTS:
      From the start of his academic training he kept a constant union with University
      and cooperated in all disciplines he had relation with before he got the
      responsibility of teaching urology. His university spirit and great formation had
      the chairman of surgical pathology see the convenience of separating urology from
      the common trunk of surgery, a proposal that, being accepted by the staff meeting
      of the Faculty of Medicine of Zaragoza and submitted to the Ministry resulted in
      the designation of urology as an independent subject in the degree of medicine.
      His labour as responsible was marked by work and continuous achievements in his
      classes, many publications, doctorate and urological monographic courses carried
      out, thesis and memories directed, all of which enabled him to create to the
      Professional Urological Specialization School, the culmination of more than 40
      years dedicated to teaching in the university. CONCLUSIONS: We find Prof.
      Romero's life completely dedicated to University and teaching. His wide
      urological and propedeutical formation made him a person who joined the necessary
      conditions and abilities to take the responsibility and carry out a satisfactory
      performance as responsible of teaching urology in the school of medicine of
      Zaragoza, a subject which thanks to his virtue and good performance was for the
      first time elevated to the level of independent subject.

PMID- 18050761
TI  - [Dr. Narciso Serrallach Mauri's Urological Records].
AB  - We present a summary of the most interesting works and commentaries by Dr.
      Norciso Serrallach Mauri, presented in Urological Records, a journal edited under
      his direction continuously from 1913 to 1935, annually or every six months. The
      state-of-the-art urological topics of the time rising the highest interest can be
      found in the journal, as well as in the publications and activities of the
      medical societies where he carried out his professional urological activity. We
      also emphasize the evaluation of his activity in relation to the estate of
      science and society at his time.

PMID- 18050762
TI  - [History of rachianesthesia and epidural anesthesia in Spain].
AB  - OBJECTIVES: To show the beginning of spinal and epidural anesthesia in our
      country and the contributions of Spanish urologists. METHODS: We reviewed books
      and writings of History of Medicine, Urology and Anesthesia and Doctoral thesis
      about spinal and epidural anesthesia. RESULTS: In the 20th century, surgeons also
      gave the anesthetic drugs to the patients. Spinal and epidural anesthesia were
      used for the first time in 1900. A lot of Spanish urologists like F Rusca
      Domenech, J.M. Batrina, M. Barragan Bonet, R. Lozano Monzon, L. Guedea Calvo, Gil
      Vernet, Fidel Pages Mirave, V Sagarra Lascurain, Gomez Ulla, etc, did research,
      writings in scientific journals and Doctoral thesis about anesthesia.

PMID- 18050763
TI  - [Field notebooks and histologic drawings in the work of Salvador Gil Vernet].
AB  - Our work is based on 11 field notebooks with his notes and descriptions of
      macroscopic and microscopic anatomic preparations. There is also one notebook
      with several handmade drawings on black lead pencil, reproducing the microscopic
      anatomy of the bladder neck; there are also five 60 x 40 cm prints with
      histologic drawings, several histologic preparations, as well as several letter
      papers with Dr. Salvador's letterhead in his various institutional aspects.

PMID- 18050764
TI  - [Birth and development of ureterorenoscopy].
AB  - In this paper we describe the history of the development of rigid
      ureterorenoscopy. It started in 1979 and today is a reality in most urological
      departments of the world. From the first ureterorenoscope with a extraordinarily
      large caliber and no dilation or operative systems, the current technique have
      developed, so that from hydraulic water pump to laser fragmentation have enabled
      to make ureterorenoscopy a common procedure for the resolution of urinary stones,
      extraction of foreign bodies in the ureter or kidney, treatment of stenosis,
      diagnosis of unilateral hematuria and endourological treatment of selected
      urothelial tumors.

PMID- 18050765
TI  - [My first steps in laparoscopic surgery].
AB  - OBJECTIVES: The author describes his first steps in laparoscopic surgery and the
      sources of some of his ideas. He thanks his father's influence and the technical
      stimuli that catalysed his scientific curiosity. For the benefit of young
      urologists at the beginning of their careers he shows how the frustrations of
      working with the early instruments became the vital challenges that inspired
      creative solutions. METHODS: His urological surgeon father inspired in his young
      son a passion for his calling. He developed an immediate and compelling interest
      in the shape and function of urological instruments like, for example, Freyer's
      lithotripter and the Iglesias resectoscope. Books of urological history and the
      works of pioneer urologists fascinated him. Watching Jose Maria Gil Vernet
      operate particularly impressed him and he says that Gil Vernet was the first
      urologist he saw using a laparoscope to diagnose an abdominal testicle. While
      working in an Oxford University hospital in 1985, he designed a balloon device to
      dissect the retropubic space. This procedure was the precursor of what several
      years later became extraperitoneal surgery The following year, he read the manual
      of Semm's laparoscopy and later described a laparoscopic varicocelectomy. In
      1993, he published the first description of a laparoscopic radical cystectomy and
      ileal conduit. In 1997, he adapted a surgical robotic system with a master-slave
      arm to carry out firstly a transurethral resection. RESULTS/CONCLUSIONS: He says
      that a good idea is beyond price because it helps the inspired individual to make
      true a long-held ambition and achieve the signal success that lifts him out of
      the mud of mediocrity.

PMID- 18050766
TI  - [Diagnosis and treatment of chronic urethritis in the military health-care system
      with the change of the century (XIX-XX)].
AB  - OBJECTIVES: We can say that in military hospitals, pioneer institutions in health
      care in our country, approximately 25% of the pathology over the second half of
      the 19th century would correspond to sexually transmitted diseases (STD), with
      hospital wards dedicated to these diseases, initially associated with
      genitourinary diseases. The "military drip" or blennorrhagic urethritis was a
      venereal disease with great incidence and prevalence in the pre-antibiotic era.
      This article reviews the diagnostic and therapeutic methods employed by Spanish
      military doctors during such period. METHODS: In the introduction we state the
      relationship between the knowledge of the time and the environment in which
      military doctors developed their professional activity. We make reference to
      military health-care journals, vehicle for their worries and demonstration of the
      level of theoretical and practical knowledge they were distinguished for. Based
      on their service records and publications we refer the urologists from the
      military health-care system that showed a greater interest in the field of
      urethral diseases, talking about the methodology they used for diagnosis and
      treatment of blennorrhagic urethritis. RESULTS AND CONCLUSIONS: Military health
      care at the end of 18th century and the beginning of the 19th century joined a
      group of professionals who demonstrated talent and perseverance in the treatment
      of "military drip". To know the concepts for the diagnosis and treatment of
      urethritis improves our perspective in the knowledge of these pathologies, and
      confirms us in the evaluation of the advances available for us today, thanks to
      the addition of efforts of our predecessors.

PMID- 18050767
TI  - [The history of extracorporeal shockwave lithotripsy in Spain].
AB  - We give a historical outline of urinary lithiasis with emphasis in the
      alternative therapeutic options to surgery. We expose the previous steps that led
      to the birth of extracorporeal shockwave lithotripsy and its implementation in
      our country.

PMID- 18050768
TI  - [Vicissitudes of a humble inventor].
AB  - Mechanized procedure for the treatment of female stress urinary incontinence.
      Retropubic fixation of the vagina with a stapler specifically designed, using the
      pubis' symphysis as the site for anchoring. We intend to demonstrate the
      physiopathologic rationale to achieve continence by anchoring the urethra. In our
      elementary conditions for research and development we could not design the
      suitable procedure, although the idea was presented to international companies.
      We summarize the development of the instrument until it was operative, filming
      one operation which was presented to the Hispanic-American Congress in Madrid
      1992. The instrument was patented in the Spanish Office of Patents and Trademarks
      in July 1992 with the category of invention patent because there were no previous
      mechanized procedures for vaginal fixation.

PMID- 18050769
TI  - [Carlos Younger de la Pena (1920-1996). "Urology in Madrid during the second half
      of the 20th century"].
AB  - Carlos Younger de la Pena (1920-1996) was one of the representative urologists of
      his time, both in urology as a whole and particularly in urology in Madrid,
      during the 40 years between 1945 to 1985. His professional training was linked to
      the department of urology in the "La Princesa" Hospital chaired by Dr. Pedro
      Cifuentes Diaz first and Luis Cifuentes Delatte posteriorly. The important
      influence of French urology led Carlos Younger to complete his studies in the
      departments of urology chaired by professors J. Cibert (Lyon), Truc (Montpellier)
      and Couvelaire (Paris). When he returned from France he completed his doctoral
      thesis with the title "Experimental study on the ureterosigmoidostomy type Coffey
      I" directed by Prof. J. Garcia Orcoyen in 1957. His first publications started in
      1946 and he ended with almost 100, including communications to various speciality
      congresses and meetings. Established in his private clinic in the Ferraz Street
      in Madrid he alternated his professional practice between Social Security
      patients and the Red Cross Central Hospital. At the end of his life he had
      collected near to 10.000 patients' clinical records. He was member of various
      scientific societies (among them the International Society Of Nephrology) and
      received various awards such as the one from the Pediatric Surgeons Association
      for his work on "bladder exstrophy "and the one from the Medical Academy of
      Valladolid for his study "Vascular renal hypertension". In 1961 he performed the
      second renal transplant in Spain. His professional interest was preferentially
      focused on uro-oncology, pediatric urology, gynecologic urology, and endoscopic
      surgery. He left many disciples with the same interests. The professional life of
      Carlos Younger de la Pena, in the period of time under analysis, is much
      significant as a reflex of the evolution of urology and urologists over half a
      century.

PMID- 18050770
TI  - [The Spanish participation in the Congresses of the International Society of
      Urology during the 20th century].
AB  - OBJECTIVES: With the occasion of the Centenary of the Constitution in 1907 of the
      International Society of Urology, initially named Association, we point at the
      topics treated and analyze the presence of the Spanish urologists in the
      foundation act as well as their role and contributions in the meetings during the
      20th century. METHODS: We obtained the data from the information in various
      periodic publications, from the memories of some participant urologists and from
      the meeting records. RESULTS: We obtained notes from the foundation meeting of
      the International Association and two congresses, and also from the 25 congresses
      of the Society. We mainly extract data from the records edited by the meeting
      secretary, about the assistance of Spanish urologists and their contribution with
      conferences or communications and also about the relevance they have had holding
      positions within the organization. CONCLUSIONS: From 1907 the presence of Spanish
      urologists both in the Association and the International Society of Urology has
      been a constant. During the first half of the century, a time when our Urology
      was in a period of consolidation, the people in charge of the main urology
      departments in big hospitals in our country where the ones that could transmit
      their experience, with a level and quality comparable with the rest of Europeans.
      During the second half, once the nations recovered from wars, the scientific
      activity continued with an increasing Spanish contribution, which extended all
      over the country with the creation of the net of Social Security hospitals. They
      had hierarchical urology departments that performed study and analysis of their
      case series and started clinical and experimental research, significantly
      increasing the number of Spanish communications, mainly in congresses celebrated
      in Spanish speaking or European cities. As a consequence of their participation,
      three of the 25 meetings organized during the 20th century have been held in
      Spain. The Spanish presence in the directing boards of the society was favoured
      by the presence of Dr. Salvador Gil Vernet to consecutive periods.

PMID- 18050771
TI  - Antiretroviral treatment: current approach and future prospects.
AB  - Pharmacologic treatment of HIV infection involves the combination of drugs that
      exert their antiretroviral effects at different stages in the life-cycle of the
      virus. Strongpublic-health programs are necessary for HIV control. To be
      successful in treating HIV, the clinician must establish a treatment alliance
      with the patient to forge optimal adherence to the treatment regimen. Potential
      adverse reactions,toxicities and drug-drug interactions must be understood and
      detected early. Disparity exists in the treatment of HIV between most African and
      western countries and can be bridged through improved access to drugs and
      treatment infrastructure. The search for a cure is led by ongoing research in
      novel concepts such as structured treatment intervention and immune-based
      therapy.

PMID- 18050772
TI  - Oral manifestation of HIV/AIDS.
AB  - The Human Immunodeficiency Virus (HIV) infection and Acquired Deficiency Syndrome
      (AIDS) have become a pandemic with about 40 million infected people world-wide.
      The virus attacks the immune cells resulting in a defective cell-mediated immune
      response thus exposing the host to opportunistic infections. Oral and peri-oral
      lesions are often seen in HIV infections and sometimes, appear as the first
      indicators of the disease. The appearance of these lesions in a known HIV
      infected person could also be a signal of the deterioration of the infection into
      a full-blown AIDS. It is therefore necessary that Health care givers should have
      a good working knowledge of the possible oral manifestations of the disease. This
      write-up highlights the clinical features and treatment of oral lesions
      associated with HIV infections.

PMID- 18050773
TI  - Responding to the HIV epidemic in the developing world. Capacity building and
      technology transfer for monitoring with HAART: a Caribbean experience.
AB  - This paper examines the concept of a developing nation that has a high HIV
      prevalence and lacks appropriate laboratory infrastructure necessary to cope with
      a treatment and care program. Several issues are discussed including personal
      experience in the context of project management for the creation and coordination
      of a facility aimed at providing the laboratory support required for the
      appropriate delivery and monitoring of HAART. Key issues about political will and
      prioritization are discussed in concert with current international guidelines and
      mechanisms of technology transfer and human resource development. The paper gives
      the benefit of the teams experience in coordinating the project, dealing
      specifically with issues such as the process of equipment procurement, staff
      recruitment, and capacity building. The need for the highest level of quality
      control and standard operating practices are discussed in the context of limited
      regional expertise and manpower support. Emphasis is placed on the long term
      objectives of operational research focusing on cheaper and simpler algorithms for
      monitoring and providing support for a comprehensive but affordable and
      sustainable program.

PMID- 18050774
TI  - Hospital treatment of HIV patients.
AB  - Treatment of patients with HIV/AIDS in Nigeria has progressed from the stage of
      inactivity, unconcern, abandonment and neglect to the present stage of holistic
      care involving treatment of the infection with Highly Active Anti Retroviral
      Agents, complications of the disease and side effects of antiretroviral therapy
      as well as that of human behavioural responses towards the disease with hope and
      promising outcome. The goal of the treatment is to prolong the patient's life
      while maintaining the best possible quality of health and life. It is now a
      continuum of care between the hospital and the different sectors of the
      community. Hospital treatment of patients with HIV-AIDS is complex and yet a
      simple task if there is healthy interaction of the patients and health care
      providers in a milieu of well equipped hospital setting with available treatment
      facilities for proper management of diseases. Similarly, for the care to achieve
      its goal, it requires a joint participation of the community and the commitment
      of the government not only on curtailment of the reservoir of HIV infection by
      antiretroviral therapy but total eradication of diseases, poverty and ignorance
      in all its entirety.

PMID- 18050775
TI  - Sociocultural aspects of HIV/AIDS infection in Nigeria.
AB  - With a population of about 134 million people distributed among 389 ethnic
      groups, Nigeria is a country of great diversity. The socio-cultural factors or
      practices in Nigeria that may be related to HIV/AIDS transmission are legion.
      These include the patriarchal family and gender differentiation, early marriage,
      polygyny, marital instability and remarriage, domestic violence, prostitution,
      scarification and other skin piercing practices, incision or cutting operations
      including circumcision, and all sorts of culturally imposed traditions and norms
      that discriminate against women. The paper discusses these phenomena with respect
      to HIV transmission and suggests imminent changes and social re-engineering that
      are essential in the era of HIV/AIDS.

PMID- 18050776
TI  - AIDS-associated malignancies.
AB  - A number of immunodeficiency states--both inherited (such as agammaglobulinaemia,
      Bloom's syndrome, hereditary telangiectasia) and acquired (e.g. immunosuppressive
      therapy) have been associated with varieties of cancers. HIV induces more
      profound immunodeficiency state and it should not be difficult to imaging why
      cancer diagnosis is made in over 40% of HIV infected patients. Impairment of
      normal function of natural killer cells as a result of lack of helper signals
      from CD4+ T-lymphocytes may be a major mechanism of increased susceptibility to
      cancer development in HIV infected patients. Although many neoplastic diseases
      could occur at a frequency not higher than would be expected by chance alone, the
      biological behaviour of such malignancies tend to be more aggressive. Three
      neoplastic diseases are associated so commonly with HIV infection that each of
      them has become recognized as an AIDS defining illness. These are Kaposi's
      Sarcoma (KS), Non-Hodgkin's Lymphoma (NHL) and Cervical Carcinoma. Both KS and
      NHL were recognized as AIDS associated cancers from the onset of the epidemic in
      1981 but carcinoma of the cervix became AIDS defining in 1993. The epidemiology,
      aetiopathogenesis, clinical manifestation, diagnostic tools and modalities of
      therapeutic intervention for KS and NHL form the subject of this review.

PMID- 18050777
TI  - A phytotherapeutic approach to Nigerian anti-HIV and immunomodulatory drug
      discovery.
AB  - Effective therapies for management of HIV infection are top priority due to the
      high rate of morbidity and mortality of the disease, globally and this has
      assumed devastating dimension in the African continent. In Nigeria, many patients
      use herbal remedies for the management of HIV/AIDS, without sufficient scientific
      proof that they possess anti-HIV activity. In this report, the role of the
      tropical rainforest plants, identified through ethnomedical approach, as a source
      of antiviral and immunomodulating agents is highlighted. Some plant derived
      antiviral and immunomodulatory agents are briefly discussed. An outline of in
      vitro antiviral and immunomodulatory assays that can be adapted to the Nigerian
      environment is given. The urgent need to identify and evaluate the medicinal
      plants in the Nigerian biodiversity reputedly used for management of viral
      infections is also emphasized.

PMID- 18050778
TI  - HIV/AIDS and the surgeon.
AB  - Human Immunodeficiency Virus and Acquired Immunodeficiency Disease (HIV/AIDS) are
      one of the most difficult challenges facing practicing surgeons worldwide. The
      challenge is more acute in sub-Saharan Africa as it currently has the highest
      prevalence of HIV infection in the world. Surgeons are at risk of occupationally
      acquired infection as a result of intimate contact with the blood and other body
      fluids of HIV patients requiring surgery. Patients also risk being infected by
      surgeons and other health care workers during surgical or dental procedures. The
      seropositive status of the majority of HIV positive patients may be unsuspected
      by the attending medical personnel who may not practice universal precautions
      against infection. The non-availability of relevant devices is however the most
      important factor militating against the use of universal precautions, especially
      in developing countries. There is therefore a need to increase the awareness
      about universal precautions and to provide the necessary devices to promote
      constant adherence to these procedures in order to reduce the risk of nosocomial
      HIV infection.

PMID- 18050779
TI  - Peripheral blood and bone marrow changes in patients with acquired
      immunodeficiency syndrome.
AB  - There is dearth of information on the haematologic complications of HIV/AIDS in
      this country. The aim of this work was to evaluate the importance of peripheral
      blood and bone marrow changes in a population of adult Nigerians managed for
      symptomatic HIV infection at the OAUTHC, Ile-Ife, between 1995 and 2001. The
      study was prospective. Peripheral blood cells counts (haemetocrit value, total
      and differential leucocyte counts, and platelet counts) and bone marrow cytology
      of serologically confirmed HIV/AIDS patients seen within the study period were
      studied. The associated opportunistic disorder (s) was noted for each patient.
      Individuals with conditions that are ordinarily associated with haematologic
      disorders (e.g. cancer and inherited haemoglobinopathies) and patients diagnosed
      in pregnancy were not included. Significant levels of differences in mean values
      of blood cells within groups were determined by student's t-test. Seventy-two
      patients were recorded, out of which 49 (68%) were evaluable. There were 32 (65%)
      males and 17 (35%) females, all aged between 21 and 51 (median = 36) years. None
      of the patients had conventional antiretroviral therapy. Lymphopenia (lymphocytes
      < 2 x 10(9)/l) was seen in 64.4% of the patients, 50% and over 40% of the
      patients had moderate-severe anaemia and neutropenia, respectively. Blood cells
      values were not significantly different between patients with mild disease and
      those with moderate-severe diseases. The most characteristic marrow abnormality
      was the abundance of naked nuclei of megakarycytes in 20 (60.1%) of the patients.
      Dysplatic changes were evident in 15 (45.5%) of the bone marrow specimens
      studied. Such changes are characterised by dysgranulopoiesis, Pelger-Huet anomaly
      in some of the mature granulocytes, vacuolation of some erythroid and myeloid
      cells, unilobular micromegakaryocytes and megaloblastic erythroid precursors
      (15.1% of the marrow).

PMID- 18050780
TI  - HIV infection among patients with pulmonary tuberculosis in Nigeria.
AB  - Respiratory problems like Pneumocystic carinni and Pulmonary tuberculosis (PTB)
      are among the common opportunistic infections in patients with HIV/AIDS. The risk
      of acquiring Mycobacterium tuberculosis in a community becomes greater with
      increase in the number of HIV positive persons with active tuberculosis. This
      study was carried out to determine the magnitude of HIV infection among PTB
      patients in different parts of Nigeria as part of the year 2000 national HIV
      surveillance programme. Blood samples were collected on blotting paper from a
      total of 2826 individuals attending TB clinics between 1st of September and 1st
      November, 2000. Samples were collected from patients with confirmed PTB from 12
      states in the 6 geopolitical/health zone (2 states/zone) of Nigeria as part of
      high risk sentinel population groups. Samples were tested for the presence of HIV
      antibodies using commercial ELISA (Genescreen HIV-1/2, Sanofi Pasteur, Paris).
      All initially reactive samples were retested with a rapid EIA (Gene II, Sanofi
      Pasteur, Paris) according to the WHO recommendations (option II). HIV Prevalence
      in the states varied from 4.2% in Oyo to 35.1% in Benue States with a median
      prevalence of 17.0%. HIV Prevalence increased with age to a peak of 23.9% among
      PTB patients 30-39 years and then declined progressively to 12.8% among those 60
      years and above. A relatively high HIV infection rate (13.8%) was found among the
      young adolescent age group 10-19 years. There was no significant difference in
      the rate among male and female PTB patients tested. Comparison with results of
      previous HIV sero-surveys shows a steady increase in HIV prevalence among PTB
      patients over the years. The high prevalence of HIV among young PTB patients aged
      10-19 years in this study is worrisome and must be noted for intervention.

PMID- 18050782
TI  - Attitudes towards community based residential care for people living with
      HIV/AIDS in Nigeria.
AB  - Community based care and support are important aspects of HIV/AIDS management in
      resource-poor African countries in view of increasing incidence of the disease
      and absence of a cure. A representative community sample (n = 2040) selected
      using a clustered stratified selection procedure was studied in Ogun, Oyo, and
      Osun states. A single item question which formed part of a larger survey of the
      stigma of mental illness was used to elicit information about the opinion of
      respondents regarding provision of a group home in their neighborhood for the
      care of persons experiencing a range of medical and social conditions which
      include HIV/AIDS, mental handicap, previous jail term, physical disability,
      mental illness, and drug abuse. Of the respondents, 906 (44.4%) were males and
      1134(55.65) were females. The mean age was 43.5 (SD 19.72). Over 71% of the
      respondents disagreed or strongly disagreed with the location of a residential
      care for persons living with HIV/AIDS (PLWHA) in their neighborhood. This level
      of rejection was only comparable to that for drug addicts and alcoholics. PLWHA's
      were more likely to be rejected than ex-convicts for whom about 55% expressed
      rejection. Decreasing education (X2 = 32.55, p < 0.003) lower income (X2 = 21.25,
      p < 0.01), urban residence of the respondents (X2 = 15.11, p < 0.05) and female
      gender (X2 = 9.25, p < 0.05) were associated with a negative attitude to such a
      residential care for PLWHA. These results suggest a deep-seated prejudice against
      the provision of a group home for the PLWHA. A community-based enlightenment
      program anchored on the nature and course of HIV/AIDS should be part of a
      holistic management approach to the disease.

PMID- 18050781
TI  - Heart disease in HIV/AIDS. How much is due to cachexia?
AB  - HIV/AIDS affects the heart through different mechanisms. Before the advent of
      HIV/AIDS, cachexia had been established as a cause of cardiac morbidity.
      Interestingly when HIV/AIDS affects the heart, not much role is ascribed to
      cachexia; one of the major criteria for diagnosis. As most electrocardiographic
      (ECG) changes in HIV/AIDS are also seen in cachexia, it became necessary to look
      at the ECG changes in HIV/AIDS in relation to body mass index (BMI). This was to
      see if any relationship existed. One hundred, 78 and 80 full blown AIDS, HIV
      positive asymptomatic and HIV negative subjects underwent 12 lead resting ECG
      respectively. Their BMI were determined from the heights and weights. BMI was
      least in the first group and highest in the last group. The mean differences
      achieved statistical significance. Systolic and diastolic blood pressures
      significantly fell from HIV negative to the AIDS patients. This was as BMI fell.
      Systolic and diastolic blood pressures fall significantly with cachexia. The
      following indices on ECG: heart rate, corrected QT interval, ST segment
      depression and T wave inversion increased from the HIV negative to the full blown
      AIDS patients. This was also the direction of reduction in BMI. Since these ECG
      changes have long been known with cachexia, it is being suggested that the
      cachexia associated with HIV/AIDS contributes to the heart disease in them.

PMID- 18050783
TI  - Characteristics of lymphocyte subsets in a normal Afro-Caribbean population and
      the implications in HIV management.
AB  - The Caribbean relies on normal lymphocyte subsets ranges established in other
      geographical locations and from different racial ethnic groups for the basis of
      the clinical management of HIV and AIDS with Highly Active Anti Retroviral
      Therapy (HAART). Normal ranges of these parameters have not been previously
      established in an Afro-Caribbean population. So we set out to determine how the
      normal lymphocyte subset ranges compare to those reported in other, races and
      geographical locations. A prospective study was done on 112 healthy Afro
      Caribbean clients who attended the Blood Collection Unit, Queen Elizabeth
      Hospital, Barbados from July 15th to November 12th 2004. Analysis for lymphocyte
      subsets was done by flow cytometry, which allows simultaneous identification and
      enumeration of total T Helper, cytotoxic T, natural killer and B lymphocyte
      cells. HIV-1, Hepatitis B and C, HTLV-1 and full blood count test were done as
      part of the normal screening routine of all blood donors. Absolute white blood
      cell counts and percentage lymphocytes for males and females were not
      significantly different, and the absolute and percentage of the T-Helper CD4
      positive lymphocyte cells were not significantly higher in females than in males.
      Absolute Cytotoxic T cell CD8 positive lymphocyte cells were higher in males than
      in females. CD56 Natural Killer cells absolute and percentage counts were higher
      in males than females however CD19 B Lympocyte absolute and percentage counts
      were not different between the two sexes in this sample population. Compared to
      published normal ranges published by the WHO and CDC, there were no significantly
      differences observed in any of the lymphocyte subsets. These finding are very
      similar to what has been reported in previous studies. We conclude that WHO/CDC
      recommendations established for the treatment and monitoring of HIV/AIDS patients
      based on CD4 levels can be safely utilized in our population.

PMID- 18050784
TI  - Demographic and social characteristics of regular donors who sero-converted in
      Harare.
AB  - Zimbabwe, like any other country, is currently experiencing a fast growing
      HIV/AIDS pandemic. A considerable number of infections are caused by blood
      transfusion. The aim of this study is to determine risk factors, events and socio
      demographic characteristics associated with incidence of HIV infections and to
      prevent sero-conversion of regular blood donor. A retrospective cross sectional
      study was done. 22,922 regular donors at National Blood Transfusion Services in
      Harare were used. The number of all regular donors who sero-converted and their
      status during the 1999 to 2001 period were determined. About 327 (1.4%) of the
      regular donors sero-converted. Two hundred and seventy-four (84%) were males and
      53(16%) were females. 52.6% of the males were married, 46.7% were single and .7%
      separated. 30.2% of the females were married, single women 67.9% and separated
      women 1.9%. Increased sero-conversion was associated with unemployment, high
      density area residence and the sexually active age group (21 to 45 year olds).
      There was an association between gender and marital status among sero-converters
      (c2 = 8.48; P-value = 0.014) and males were likely to be older than females (t =
      2.9; P-value = 0.0019). It can be concluded that unemployment and living in high
      density residential areas are highly associated with HIV sero-conversion among
      regular donors. Single females, working class males and the sexually active age
      group are highly exposed to risk factors. It is recommended that donor education
      schemes and knowledge of these factors should be considered during donor
      recruitment.

PMID- 18050785
TI  - Partner disclosure of HIV status among HIV positive mothers in Northern Nigeria.
AB  - Partner consent and support can substantially enhance adherence to PMTCT
      interventions. This study explores the issues concerning disclosure of HIV status
      to partners of HIV sero-positive mothers in a PMTCT programme in Jos, Northern
      Nigeria. Previously field-tested questionnaires were administered by trained
      counsellors to 570 consenting HIV positive mothers who were participating in the
      PMTCT programme at Jos University Teaching Hospital (JUTH), Jos. The findings
      were entered into Epi Info and analysed using frequencies. The median age of
      respondents was 29 years while that of their partners was 37 years. Five hundred
      and fifty-five (99.5%) of respondents were married. Majority of the women were
      Christians (82.9%) while 16.9% were Moslems. Seventy four percent (419/563) of
      the mothers were aware of their husband's HIV sero-status. Of these, 65.4%
      (274/419) of the partners were HIV positive while 34.6% were sero-negative.
      Eighty nine percent (500/560) of the women have disclosed their HIV status to
      their partners. Of these, 39.6% (199/502) required the assistance of health
      workers while 59.4% (298/502) did it by themselves. Following disclosure of HIV
      status, 86.9% (430/495) of the partners were supportive, 5.7% were indifferent,
      6.7% were quarrelsome and abusive while 1.0% was violent. The reactions of
      partners of HIV positive mothers to disclosure of their wives' HIV status are
      predominantly supportive. This should strengthen strategies to promote partner
      disclosure.

PMID- 18050786
TI  - HIV status of partners of HIV positive pregnant women in different regions of
      Nigeria: matters arising.
AB  - This study was conducted to determine the pattern of HIV sero-status of Partners
      of HIV Positive Pregnant Women in three different regions of Nigeria and to
      explore the implications for HIV prevention interventions. The Site Coordinators
      of PMTCT programs in three Nigerian cities obtained data of the HIV status of the
      partners of HIV positive pregnant women. The selection of Benin City, Jos and
      Kano was made after consideration of their ethnic, religious and cultural
      representation of Nigeria. Benin City represents a traditional southern Nigeria
      city, Kano a traditional northern city and Jos, a middle-belt, ethnically diverse
      cosmopolitan setting. The data were analyzed using frequencies. A total of 500
      partners of HIV infected pregnant women were tested for HIV using Determine
      Abbott test kits. Positive results were confirmed using Western blot or a second
      rapid test kit. The city-by-city results showed that in Benin City (Southern
      Nigeria), 78.8% (104/132) of the partners were HIV negative (sero-discordant),
      Jos (Middle-Belt) had 48.4% (103/213) sero-discordance while Kano (Northern
      Nigeria) recorded a sero-discordance rate of only 7.7% (12/155). These results
      indicate that the dynamics of HIV transmission in marital settings in Nigeria are
      different in the various regions of the country. Socio-cultural and religious
      settings play a significant role in HIV transmission among couples. These
      findings should guide prevention interventions in order to achieve maximal
      impact.

PMID- 18050788
TI  - Ethical issues in HIV/AIDS research, counselling and testing in Nigeria.
AB  - HIV/AIDS is a major pubic health problem in Nigeria. This paper identifies the
      ethical issues involved in HIV/AIDS biomedical and behavioural research,
      counselling and testing in the country. These concerns are discussed in the
      context of the three universal ethical principles of respect for persons,
      beneficence, and justice. Written informed consent, which is a component of
      respect for persons, is a challenge in Nigeria because of skepticism to
      documentation, sensitivity of sexual practices often explored in behavioural
      research, and a tradition that discourages patients from questioning medical
      authority. Although monetary inducement of research participants is ethically
      acceptable, the high levels of poverty in Nigeria raise concerns that payment of
      money may unduly induce indigent participants to enroll in research. The
      disclosure of results in situations when married HIV positive persons insist that
      their status should not be revealed to their spouse illustrate the dilemma that
      health workers face in adhering to the ethical norm of keeping confidentiality
      and the public health obligation of preventing HIV transmission in a third party.
      Some recommendations are offered to address these concerns.

PMID- 18050787
TI  - Reliability of testing and potential impact on HIV prevention in Nigeria.
AB  - Several factors including variability of human immunodeficiency virus (HIV),
      laboratory facilities, cost and competence of personnel handling the tests are
      some of the important factors that affect accuracy and reliability of HIV testing
      in most parts of Africa. Recently investigators in Africa have observed that
      antibody detection assays based on antigens derived from HIV-1 subtype B show
      moderate to significantly lower sensitivity for detection of infection by various
      non-B subtypes. In this study, we evaluated the reliability of two EIA and 12
      rapid HIV-1/2 test kits that are commercially available in Nigeria using the
      Western immunoblotting technique as reference. A panel of 100 sera from Western
      blot confirmed symptomatic or asymptomatic HIV-1 infected persons and 90
      seronegative patients from those referred for testing in our laboratory were used
      for this study. Each sample was tested with two HIV-1/2 EIA, and 12 HIV-1/2 rapid
      test kits commercially available at one time or the other for HIV-1/2 testing in
      Nigeria. Overall, the sensitivity of the two EIA kits were 100% and 91.0% with
      specificity of 96.7% and 91.1% respectively. The sensitivity of the rapid test
      kits ranged from 88% to 98.0% with specificity of 92.2% to 100%. Further analysis
      showed significant variation in the sensitivity and specificity of the same kit
      based on whether an individual had asymptomatic or symptomatic infection The
      results of this study highlight the problem of diagnosis of HIV infections in
      Africa. It shows that the sensitivity of most of the rapid assays shall not be
      adequate for detection of early infection. The implications of possible
      misdiagnosis on the various intervention strategies that rely predominantly on
      correct HIV status of an individual are enormous. Thus, there is an urgent need
      for review of the current HIV testing assays or algorithms in Nigeria and other
      parts of Africa.

PMID- 18050789
TI  - Association between sexual violence and psychiatric morbidity among HIV positive
      women in South Africa.
AB  - This study examined the association between rape and psychiatric morbidity among
      recently diagnosed HIV-infected women in South-Africa. One hundred and five women
      attending an out-patient infectious disease clinic of the Department of Internal
      Medicine, Tygerberg Hospital, Cape Town, South-Africa participated in the study.
      Full medical as well as socio-demographic histories were obtained for each
      patient. Psychiatric morbidity was assessed with the MINI International
      Neuropsychiatric Interview (MINI). Life-time prevalence of rape among the women
      was 4.8%. A significant relationship was found between rape and (i) drug
      dependence (X2 = 40.77, P < 0.00), (ii) alcohol dependence (X2 = 14.37, P <
      0.01), (iii) post traumatic stress disorder (X2 = 8.91, P < 0.02), and (iv) major
      depression (X2 = 4.57, P < 0.05). Women who were raped were more likely to be
      younger (t = 2.86, P < 0.05), Afrikaans-speaking (X2 = 7.39, P < 0.02), and
      unemployed (X2 = 6.42, P < 0.04). HIV positive women with a history of having
      been raped may experience a number of psychiatric disorders. As part of the
      comprehensive medical care of HIV, it is important that health workers assess
      past sexual abuse and current psychiatric symptoms.

PMID- 18050790
TI  - Wireless networks for surveillance, data capture and data management in the human
      immunodeficiency virus epidemic care and treatment programmes.
AB  - Biomedical and demographic data capture and the subsequent management of such
      information are critical factors in the implementation of any level of healthcare
      prevention and treatment program. The developing world is seriously handicapped
      by lack of infrastructure to acquire such data let alone manipulate the
      information banks for projections, forecasting and priority project planning.
      With this in mind we set about to use the recent proliferation of wireless
      cellular networks and easily accessible Personal Digital Assistants (PDA), to
      devise a means of collecting such data even from the most remote primary
      healthcare facility. Our priority is aimed at initially at providing a support
      technology for the HIV expanded program. This technology can be implemented in
      the absence of computerization and regular power supply. Utilizing a PDA to
      capture patient data (demographic, clinical and laboratory parameters), the
      healthcare giver can use a wireless link between the PDA and a cellular phone to
      transfer the data to a central medical data base. These can then become permanent
      and secure data banks for future use by health providers, either at the same
      location or at other health facility that have authorized access to the data
      bank. It also affords a platform for integrating reference labs into the network
      as well as the opportunity to disseminate continuing medical educational
      material. The network can also be adapted to electronic remote consultations and
      eventually its data banks can be assimilated into protocols of artificial
      intelligence and data mining.

PMID- 18050791
TI  - Dry cat food.

PMID- 18050792
TI  - An ethicist's commentary on veterinarians and animal welfare.

PMID- 18050793
TI  - Factors affecting Canadian veterinarians' use of analgesics when dehorning beef
      and dairy calves.
AB  - Data collected through a national, randomized mail survey (response rate 50%)
      were used to identify reasons why veterinarians were likely (i) to use analgesic
      drugs when dehorning calves, and (ii) to perceive dehorning without analgesia as
      very painful. Logistic regression analysis indicated that veterinarians were more
      likely to be analgesic users the more they perceived that dehorning without
      analgesia was painful (OR = 1.7, P < 0.001). Other positive influences were if
      the veterinarian worked in British Columbia or Alberta (OR = 5.9, P = 0.005), and
      if they were primarily in dairy practice (OR = 3.7, P = 0.012) rather than beef
      practice. This effect of dairy practice was negated if the veterinarian also
      perceived that owners were unwilling to pay for analgesia (interaction term: OR =
      0.25, P = 0.038). Veterinarians were also less likely to perceive dehorning
      without analgesia as very painful if they perceived that owners were unwilling to
      pay (OR = 0.58, P = 0.029). However, this effect on pain perception was offset by
      concern for personal safety (OR = 2.7, P = 0.015). The results are consistent
      with the relatively high level of outreach about animal welfare among farmers and
      veterinarians in the western provinces. The results confirm that many
      veterinarians' approach to pain management for dehorning is influenced
      considerably by concern about cost. However, pain management for dehorning is not
      expensive and there is unequivocal evidence that dehorning calves without pain
      management causes significant distress. Continuing education of veterinarians
      should help to increase analgesic usage.

PMID- 18050794
TI  - Factors associated with West Nile virus disease fatalities in horses.
AB  - In 2003, the occurrence and location of horses with clinical signs of West Nile
      virus infection were identified in the southern portion of Saskatchewan with the
      help of veterinarians, owners, and the regional laboratory. A total of 133
      clinical cases were reported between July 30 and September 19, 2003; however,
      postseason surveillance suggests that the number of cases was underestimated. The
      case fatality rate was 43.8% (95% CI 35.2, 52.4). Factors associated with
      fatality in clinical cases included sex, week of onset of clinical signs, and
      coat color. Reported clinical cases clustered within regional health authority
      districts, suggesting regional differences in geographic factors, potentially
      including climate and mosquito control, that could contribute to the risk of
      disease. However, most of the variation in the risk of fatality in clinical cases
      is explained at the individual level rather than the Regional Health Authority
      level, which suggests the outcome of clinical disease is primarily determined by
      characteristics of, or management factors affecting, the individual horse.

PMID- 18050795
TI  - Evidence of Parelaphostrongylus tenuis infections in free-ranging elk (Cervus
      elaphus) in southern Ontario.
AB  - The antemortem detection of a Parelaphostrongylus tenuis infection in a free
      ranging wild elk (Cervus elaphus) in southern Ontario is documented. Postmortems
      on other free-ranging elk that died during 2000-2005 indicated that 59% (17/29)
      were infected with P. tenuis, based on presence of lesions in the brain.

PMID- 18050796
TI  - Actinomyces endophthalmitis and pneumonia in a dog.
AB  - Actinomyces endophthalmitis and pneumonia were diagnosed in a young rottweiler
      that was presented with lethargy, weight loss, right blepharospasm, and ocular
      discharge. The affected eye was enucleated, and the pneumonia was treated
      successfully with systemic antibiotics.

PMID- 18050797
TI  - Immune mediated neutropenia and thrombocytopenia in 3 giant schnauzers.
AB  - Neutropenia, thrombocytopenia, and splenomegaly were recognized in 3 adult female
      giant schnauzers. Antineutrophil antibodies were demonstrated in 2 dogs.
      Following splenectomy, administration of prednisone and azathioprine resulted in
      normalization of neutrophil and platelet numbers in all dogs.

PMID- 18050798
TI  - Change in blood antioxidant status of horses moved from a stable following
      diagnosis of equine motor neuron disease.
AB  - The antioxidant status of 10 horses living in stable 1 where 2 cases of equine
      motor neuron disease had previously been diagnosed was assessed before and 9
      weeks after moving to another stable. Duration of residence in stable 1,
      subsequent moving, or both, significantly affected several parameters of the
      antioxidant status.

PMID- 18050799
TI  - Osteosarcoma in a 6-year-old Newfoundland dog: limb-sparing surgery and cisplatin
      chemotherapy.
AB  - A 6-year-old Newfoundland dog was presented with left forelimb lameness, which
      was diagnosed as osteosarcoma and treated with an endoprosthetic limb-spare
      surgery and cisplatin chemotherapy.

PMID- 18050800
TI  - The United States' prohibition of horsemeat for human consumption: is this a good
      law?

PMID- 18050801
TI  - How much is your practice worth? CVMA practice value estimate.

PMID- 18050802
TI  - Ancylostoma caninum infection in a Texas-born Blue Lacy dog--Alberta.

PMID- 18050803
TI  - Radiation therapy of canine nontonsillar squamous cell carcinoma.

PMID- 18050804
TI  - Diagnostic ophthalmology. Anterior uveal neoplasia and anterior uveitis.

PMID- 18050806
TI  - Combined phacovitrectomy for macular hole: long-term results.
AB  - BACKGROUND AND OBJECTIVE: To present the long-term results of patients undergoing
      combined phacovitrectomy surgery for idiopathic macular hole at a single center.
      PATIENTS AND METHODS: A retrospective review of the records for 57 eyes of 53
      consecutive patients who underwent combined phacovitrectomy for idiopathic
      macular hole during an 18-month period was completed at the Southampton Eye Unit.
      RESULTS: In 45 of 57 eyes (78.9%), the macular hole closed after one surgical
      procedure. Forty-seven patients had a follow-up period of more than 12 months
      (mean = 22.1 months). In this group, the mean visual acuity (standard deviation)
      improved by 0.37 (+/- 0.46) logarithm of the minimum angle of resolution units.
      Thirty-two (68%) cases had improved visual acuity of 2 or more Snellen lines.
      Hole closure rate at the final follow-up examination was 87.2%. CONCLUSION:
      Combining phacoemulsification and vitrectomy for an idiopathic macular hole has
      many benefits. It is a safe procedure and produces long-term results that are
      comparable to previously published series.

PMID- 18050805
TI  - Endophthalmitis caused by staphylococcus epidermidis: in vitro antibiotic
      susceptibilities and clinical outcomes.
AB  - BACKGROUND AND OBJECTIVE: To investigate the antibiotic sensitivities and
      clinical outcomes of eyes with endophthalmitis caused by methicillin-sensitive
      versus methicillin-resistant Staphylococcus epidermidis (MSSE/MRSE). PATIENTS AND
      METHODS: A retrospective, consecutive case series of all patients with
      endophthalmitis caused by S. epidermidis from January 1, 1996, through July 1,
      2004, was conducted. The antibiotic sensitivities and clinical outcomes were
      obtained from the corresponding medical records. RESULTS: The study included 86
      eyes of 86 patients with S. epidermidis endophthalmitis (34 MSSE and 52 MRSE).
      Endophthalmitis categories included cataract surgery (58), glaucoma surgery (12),
      trauma (7), vitrectomy (4), penetrating keratoplasty (4), and corneal suture
      ulcer (1). In vitro testing revealed that all MSSE and MRSE isolates were
      sensitive to vancomycin, 67% of MSSE isolates and 67% of MRSE isolates were
      sensitive to gatifloxacin, and 73% of MSSE isolates and 67% of MRSE isolates were
      sensitive to moxifloxacin (overall 68% sensitive). All eyes were treated with
      intravitreal vancomycin and either ceftazidime or amikacin. Visual acuity
      improved to a median of 20/80 at 3 months and 20/60 at 1 year. I CONCLUSIONS: In
      the current study, all MSSE and MRSE isolates were sensitive to vancomycin and
      68% were sensitive to the fourth-generation fluoroquinolones. There were no
      significant differences in visual acuity outcomes of endophthalmitis caused by
      MSSE versus MRSE isolates.

PMID- 18050807
TI  - Effect of the preservation-to-surgery interval on corneal allograft survival in
      low-risk patients.
AB  - BACKGROUND AND OBJECTIVE: To investigate the role of the preservation-to-surgery
      interval on corneal allograft survival in low-risk patients. PATIENTS AND
      METHODS: Eighteen donor corneas obtained from an overseas eye bank were preserved
      and transported overseas in Optisol-GS solution (Chiron Vision, Irvine, CA) in
      Group 1. Thirty fresh, young, healthy, and unscreened donor corneas soaked in the
      same medium were used in Group 2. Average preservation-to-surgery time was more
      than 8 days in Group 1 and less than 30 hours in Group 2. Corneal allograft
      survival rates were determined by Kaplan-Meier estimates of the survivor
      functions. The log-rank test was used to determine statistical significance of
      the differences between groups. was 233.3 +/- 37.7 hours in Group 1 and 20.8 +/-
      4.6 hours in Group 2 (P < .05 for the comparison of average times). There were
      significant differences between the groups with respect to donors' age and
      enucleation time, but there were no statistically significant differences between
      the groups in terms of graft diameter and recipient diameter or for corneal
      allograft survival in low-risk patients. The graft survival rate was 83.3% in
      Group 1 and 93.3% in Group 2 at the end of the follow-up period. CONCLUSIONS:
      Preservation-to-surgery time has no effect on corneal allograft survival in low
      risk patients. However, prospective, randomized, long-term and large-scale
      clinical trials are necessary to confirm these findings.

PMID- 18050809
TI  - Surgical outcomes of traditional limbal-based versus fornix-based trabeculectomy
      with corneal valve.
AB  - BACKGROUND AND OBJECTIVE: To compare the safety and efficacy of fornix-based
      trabeculectomy with corneal valve to traditional limbal-based trabeculectomy with
      mitomycin C (MMC) in eyes with open-angle glaucoma. PATIENTS AND METHODS: In this
      retrospective, nonrandomized, comparative study, 42 eyes that underwent limbal
      based trabeculectomy with MMC were compared with 32 eyes with fornix-based
      trabeculectomy with corneal valve with MMC. Success was defined as final
      intraocular pressure (IOP) of at least 20% less than preoperative IOP and between
      5 and 22 mm Hg. mean IOPs were 23.5 +/- 12.2 and 11.5 +/- 5.3 mm Hg,
      respectively, in the limbal-based group and 24.8 +/- 11.1 and 11.7 +/- 2.5 mm Hg,
      respectively, in the fornix-based group (P < .001 and P = .85, respectively). The
      fornix-based group had significantly less hypotony (3% vs. 21%, P < .05).
      CONCLUSIONS: Fornix-based corneal valve trabeculectomy with posterior placement
      of MMC sponges provides IOP control comparable to limbal-based traditional
      trabeculectomy, with decreased incidence of hypotony.

PMID- 18050808
TI  - Surgical and functional results of augmented superior oblique muscle z-tenotomy
      in patients with superior oblique overaction and Brown's syndrome.
AB  - BACKGROUND AND OBJECTIVE: To compare the effectiveness of augmented superior
      oblique Z-tenotomy (SOZT) with fixed standard SOZT in canceling preoperative
      superior oblique overaction associated with A pattern anisotropia or V pattern in
      Brown's syndrome. PATIENTS AND METHODS: Sixteen consecutive patients with
      superior oblique overaction or Brown's syndrome were treated by removal of a
      triangular piece of the superior oblique tendon near its insertion (augmented
      SOZT). Outcome was compared with 20 consecutive historical controls after
      standard SOZT. RESULTS: The decrease in superior oblique overaction in the right
      and left eyes and fundus intorsion and the collapse of A pattern anisotropia were
      more significant for patients with superior oblique overaction (P = .003, P =
      .007, P = .05, P = .0015, respectively) and patients with Brown's syndrome (P =
      .025, P = .03, and P = .05, respectively). No study patient with superior oblique
      overaction and A pattern anisotropia required reoperation compared with 5 of 14
      controls (37.5%); rates for patients with Brown's syndrome were 0 for the study
      group and 3 of 6 (50%) for the control group. CONCLUSIONS: Augmented SOZT is
      superior to standard SOZT for correcting superior oblique overaction, intorsion,
      A or V pattern, and stereopsis. It is not associated with complications or
      reoperation. The size of the Z-tenotomy can be modified according to the
      intraoperative assessment to achieve symmetric results.

PMID- 18050810
TI  - Can optical coherence tomography predict the outcome of laser photocoagulation
      for diabetic macular edema?
AB  - BACKGROUND AND OBJECTIVE: To assess the outcome of laser photocoagulation in
      patients with diabetic macular edema. PATIENTS AND METHODS: Forty-seven patients
      (51 eyes) with clinically significant macular edema (CSME) undergoing grid laser
      photocoagulation were included. Clinical examination and optical coherence
      tomography (OCT) were performed at baseline and 3 to 4 months after treatment.
      The central foveal thickness, mean inner macular thickness (average retinal
      thickness in fovea and inner macular circle), and mean macular thickness were
      calculated. Based on the greatest OCT thickness at baseline, patients were
      grouped according to mild (< 300 microm; Group 1), moderate (300 to 399 microm;
      Group 2), and severe (> or = 400 microm; Group 3) macular edema. RESULTS: Group 2
      showed significant reductions in central foveal thickness (23 microm, P = .02),
      mean inner macular thickness (18 microm, P = .02), and mean macular thickness (9
      microm, P = .04) with slight improvement in visual acuity. Groups 1 and 3 did not
      show any significant change in macular thickness values and there was a
      statistically insignificant worsening of visual acuity in these groups.
      CONCLUSIONS: Patients with moderate macular thickening of 300 to 400 microm
      benefit most from laser treatment. OCT may help in choosing the appropriate
      treatment for CSME based on the degree of macular thickening. Long-term studies
      are warranted to confirm these findings.

PMID- 18050811
TI  - Diode laser-induced mitosis in the rabbit retinal pigment epithelium.
AB  - BACKGROUND AND OBJECTIVE: The induction of retinal pigment epithelium (RPE)
      proliferation without damaging the inner layers of the retina might be helpful in
      patients with RPE atrophic changes and degeneration. This study aimed to induce
      mitosis in the RPE of the rabbit after subthreshold photocoagulation with the
      diode laser. MATERIALS AND METHODS: Twenty-five male Dutch rabbits received
      retinal photocoagulation using an 810-nm diode laser with different power
      settings and exposure times. The eyes were processed for light microscopy,
      electron transmission microscopy, and immunohistochemistry. RESULTS: Neither
      morphological alterations nor mitotic activity was found after 5-mJ energies.
      Retinal layers were not affected and RPE hyperplasia appeared in the treated
      areas associated with mitotic activity when 10 mJ was used. Mitosis induction and
      retinal damage appeared with 20, 50, and 100 mJ and were associated with
      ophthalmoscopic damage. CONCLUSIONS: The use of subthreshold 810-nm diode laser
      treatment may induce mitosis in the RPE without causing damage to the neighboring
      layers.

PMID- 18050812
TI  - Light flashbacks during retinal laser photocoagulation following fluorescein
      angiography.
AB  - BACKGROUND AND OBJECTIVE: Yellow light flashbacks can often be seen in cases of
      laser photocoagulation performed shortly after fluorescein angiography. To
      determine whether unblocked secondary emission from retained aqueous and vitreous
      fluorescein may be reaching the treating ophthalmologist, the absorption
      characteristics of serial dilutions of sodium fluorescein were studied at
      wavelengths similar to the output of the krypton laser. MATERIALS AND METHODS: A
      Unicam sp500 series II visible spectrophotometer (Pye Unicam Ltd., Cambridge, UK)
      was used to measure fluorescein absorption at serial dilutions ranging from
      100,000,000 to 100 ng/mL at 488, 518, 568, and 647 nm. sive dilution of
      fluorescein concentration and with increased wavelength. Blue (488 nm) and green
      (518 nm) light absorbed at all dilutions of fluorescein. Yellow light (568 nm)
      did not show any significant absorption below a concentration of 100,000 ng/mL
      and red light (647 nm) absorbed little below a concentration of 3,000,000 ng/mL.
      CONCLUSIONS: Dilutions of fluorescein absorbed all commonly used laser
      wavelengths. There is concern that fluorescein absorption results in emission of
      light at 520 nm (range: 450 to 700 nm), which may not be blocked by the filters
      currently placed in fixed laser delivery systems.

PMID- 18050813
TI  - Leuprolide acetate and central retinal vein occlusion.
AB  - A 63-year-old man suffered a central retinal vein occlusion 2 months after he
      began taking leuprolide acetate for prostate cancer. Despite control for possible
      systemic hypertension (126/90 mm Hg) and mild hypercholesterolemia (total
      cholesterol level =246 mg/dL [range: 16 to 200 mg/dL], high-density lipoprotein
      level =67 mg/dL [range: 40 to 59 mg/dL], and low-density lipoprotein level =144
      mg/dL [range: 0 to 130 mg/dL]), progression of the venous occlusive disease
      occurred. Leuprolide acetate, which is associated with thromboembolic events and
      diffuse intravascular coagulation, may be implicated in central retinal vein
      occlusion.

PMID- 18050814
TI  - Combined panretinal photocoagulation and cataract surgery in a patient with
      diabetes mellitus.
AB  - A case is presented whereby a simple method of applying indirect laser during
      cataract surgery in the presence of retinal and iris neovascularization is
      described. The method involves placing an infusion cannula into the anterior
      chamber following standard phacoemulsification and soft lens matter removal. The
      main section is then sutured and indirect laser is delivered to the far retinal
      periphery with gentle manipulation of the eye. Successful delivery of indirect
      panretinal photocoagulation despite inadvertent vitreous loss in this case
      demonstrates the advantages of its use. Other advantages, including its use in
      previously vitrectomized eyes and allowing manipulation/indentation of the eye,
      control of bleeding, and better visualization, are discussed.

PMID- 18050815
TI  - Serous retinal detachment following glaucoma surgery.
AB  - The authors report the occurrence and clinical course of serous retinal
      detachment following glaucoma surgery in three patients. Serous detachment
      resolved in all patients spontaneously following treatment with oral and topical
      steroids.

PMID- 18050816
TI  - In vivo evidence of hypotrophic ciliary body in ocular ischemic syndrome by
      ultrasound biomicroscopy.
AB  - In ocular ischemic syndrome, the ischemic condition is due to markedly reduced
      blood flow and increased vascular resistance of retrobulbar circulation, as in
      the central retina and posterior ciliary arteries. Chronic hypoxia affects even
      the iris and ciliary body. The hypoperfusion of the ciliary body leads to a
      relative hypotony, presumably related to decreased aqueous humor production.
      Histopathologic study has demonstrated ciliary body atrophy on an ischemic basis.
      The authors used ultrasound biomicroscopy to demonstrate in vivo the hypotrophic
      condition of the ciliary body in ocular ischemic syndrome.

PMID- 18050817
TI  - Prolonged exposure of intraocular lens implant with preservation of globe
      integrity and visual function.
AB  - A 70-year-old woman had corneal ulcer and melting after complicated cataract
      surgery with polymethylmethacrylate lens implant insertion. A conjunctival flap
      was initially used to cover the defect with a plan to perform keratoplasty later.
      Fifteen months postoperatively, she presented with total absence of central
      corneal tissue and iris and exposure of the implant. The eye was not inflamed,
      painful, or hard on palpation and visual acuity was counting fingers at 3 m. The
      preservation of globe integrity despite exposure of the polymethylmethacrylate
      implant implies a stable adhesion between polymethylmethacrylate and residual
      corneal tissue and may prove useful in keratoprosthesis design.

PMID- 18050818
TI  - Optical coherence tomography demonstration of Best's vitelliform macular
      dystrophy in a child.
AB  - Considering the importance of optical coherence tomography in clinical decision
      making, the veracity of these images is critical. The authors describe a 5-year
      old girl with Best's vitelliform macular dystrophy of different stages of
      development in both eyes in which the optical coherence tomography appearance
      correlated well with both the staves of the disease and the visual function.

PMID- 18050819
TI  - Optical coherence tomography of corneal and scleral melts.
AB  - Corneal and scleral melts can be difficult to assess by slit-lamp due to the
      overlying opacity. The authors demonstrate the role of optical coherence
      tomography (OCT) in the diagnosis and management of two cases of corneal and
      scleral melt. A high-speed anterior segment OCT system operating at a 1310-nm
      wavelength was used. Cross-sectional OCT images showed the depth and extent of
      the melt. OCT images were obtained through an opaque pannus in one case and
      through a calcium plaque in the other. OCT images at the follow-up examination
      revealed a thin fluid space between the amniotic graft and cornea and its
      subsequent resolution in the first case and the fits of an epicardial graft and a
      subsequent clear lamellar corneal graft in the second case. OCT images allow
      physicians to assess melts through opaque media and subsequent graft integration
      after repair.

PMID- 18050820
TI  - The effect of myopia on the position of the ora serrata.
AB  - This article evaluated the effect of myopia on the position of the ora serrata
      relative to the extraocular muscle insertions. In this prospective case series,
      11 patients were evaluated during scleral buckling procedures. Intraoperative
      measurements of the distance from the ora serrata to the muscle insertion in each
      quadrant were compared to baseline refractive error. The distance between the ora
      serrata and the muscle insertion increased with increasing myopia superonasally
      and inferonasally. The surgeon must be aware of the need to position a scleral
      buckle more posteriorly with increasing myopia to avoid improper scleral buckling
      position and consequent surgical failure.

PMID- 18050821
TI  - Capsulorhexis in white cataract using a green-light endoillumination probe.
AB  - The authors describe a technique for performing a safe and controlled continuous
      curvilinear capsulorhexis (CCC) in white cataracts using the contrast-enhancing
      effect of green light from an endoillumination probe. After attaching a green
      filter to the endoillumination unit of the vitrectomy set, a CCC was performed
      under the green light of the endoillumination probe, which was placed on the
      periphery of the cornea in a manner that followed the tearing edge of the
      capsulorhexis. This technique may be an alternative to capsular dyes in
      performing a safe and controlled CCC in white cataracts.

PMID- 18050822
TI  - Lightweight autoclavable wide-angle contact lens for vitreous surgery.
AB  - The authors describe an autoclavable, self-stabilizing, lightweight wide-angle
      contact lens for vitrectomy. The lens has two optical pieces with perforated
      plastic casing to sustain a high temperature (150 degrees C) for autoclaving. The
      lens has a 106 degrees static and 127 degrees dynamic field of view. The
      footplates and reduced weight (2.4 grams) due to the plastic casing allow self
      stabilization of the lens. The open lens design.with high temperature resistant
      plastic prevents fogging during autoclaving and surgery. The autoclavable, self
      stabilizing, lightweight wide-angle contact lens allows visualization of the
      peripheral retina during surgery and faster sterilization by autoclaving between
      surgeries without the disadvantage of lens fogging.

PMID- 18050823
TI  - Illuminated curved vitrectomy probe for vitreoretinal surgery.
AB  - A new self-illuminated and curved vitrectomy probe was designed for better
      accessibility of the peripheral retina, particularly in phakic patients. This
      probe has a 20-gauge pneumatic cutter. The curvature at the shaft has a 19.4-mm
      radius and is 25 mm long. A 2.5-cm piece of polyethylene terephthalate tubing
      (heat-shrink tubing) is threaded over both the probe and the 0.5-mm diameter
      fiberoptic light source to assemble the illuminated probe. Use of this instrument
      avoids inadvertent trauma to the clear lens in phakic eyes and allows the surgeon
      to illuminate the anterior vitreous with one hand while the other hand can be
      used to depress the sclera. This instrument complements wide-angle viewing for
      safe and quick surgical treatment of peripheral retinal pathology in phakic
      patients.

PMID- 18050824
TI  - Omental torsion secondary to right inguinal hernia: case report and cumulative
      review of the English literature.
AB  - A case of omental torsion secondary to right inguinal hernia in a 51-year-old man
      was operated on in Naga Hospital. Preoperative computed tomography (CT) showed a
      characteristic whirling fatty mass and entering into a right inguinal hernia.
      Omental torsion is a relatively rare disease, and the preoperative diagnosis is
      difficult because of nonspecific clinical signs and symptoms. In this report, we
      gathered 36 patients with omental torsion from the English language literature
      since 1986, with the addition of the patient herein reported, and clarified the
      symptoms, imaging findings, and management of omental torsion.

PMID- 18050825
TI  - Experimental study of Composix mesh for ventral hernia.
AB  - We aimed to compare conventional single-layer mesh and composite mesh in terms of
      the degree of tissue repair on the abdominal wall side of the mesh and the degree
      of mechanical adhesion to the intestine and to confirm the stability of composite
      mesh. We used a single-layer polypropylene (PP) mesh and a two-layer Composix
      mesh (E/X type) consisting of a PP mesh and an expanded polytetrafluoroethylene
      mesh. Twenty rats were divided into two groups. Three months after mesh
      placement, histopathologically, ingrowth of granulation tissue into the mesh on
      the abdominal wall side was prominent without mesh shrinkage or shift in either
      group. In the PP mesh group, 50% of the rats had firm adhesions between the mesh
      and the intestine, whereas the Composix mesh group had no adhesions to the
      intestine. Unlike conventional PP mesh, Composix mesh prevented adhesions to the
      intestine on the peritoneal side without impairing tissue union with the visceral
      peritoneum, suggesting its usefulness in clinical onlay mesh repair for ventral
      defects.

PMID- 18050826
TI  - Laparoscopic management of gallbladder duplication.
AB  - Gallbladder duplication is a rare condition. Because laparoscopic cholecystectomy
      is the primary treatment modality for the diseased single gallbladders, it should
      be the choice of treatment for double gallbladders. However, preoperative imaging
      methods may be unsatisfactory for the correct diagnosis. As a result, incomplete
      resections may be performed. Intraoperative cholangiography should be performed
      in suspected cases to prevent inadvertent injury to the biliary system. In this
      report, we present a symptomatic patient with double gallbladders with separate
      cystic ducts in whom the gallbladders were successfully resected as a single
      specimen by laparoscopic means. The pitfalls of diagnostic modalities and
      surgical strategy are discussed in the context of the available literature.

PMID- 18050827
TI  - Mirizzi syndrome in a patient with anomalous connection of the cystic duct into
      the right hepatic duct.
AB  - In 1948, Mirizzi described a syndrome characterized as the obstruction of the
      common hepatic duct by a stone located in the gallbladder's neck or in the cystic
      duct. We present a rare case of Mirizzi syndrome resulting from a fistula
      involving the cystic duct, the neck of the gallbladder, and the right hepatic
      duct. This finding was possible because the patient had a rare biliary anatomic
      variation: the insertion of the cystic duct straight in the right hepatic duct.
      The diagnosis was suggested by abdominal ultrasonography and confirmed by
      endoscopic retrograde cholangiopancreatography. The surgical approach was
      performed by means of an open cholecystectomy, common biliary duct exploration
      using the right hepatic duct and a transduodenal papillotomy, and insertion of a
      long limb T-tube through the right hepatic duct to drain the common duct. The
      procedure was successful, and after an 18-month period, the patient is free of
      symptoms.

PMID- 18050828
TI  - Irinotecan hydrochloride (CPT-11) and cisplatin as first-line chemotherapy after
      initial surgery for ovarian clear cell adenocarcinoma.
AB  - Patients with ovarian clear cell adenocarcinoma (OCCA) show a poor response to
      conventional platinum-based chemotherapy. Recently, it was reported that
      combination chemotherapy with cisplatin plus irinotecan hydrochloride (P-CPT)
      achieves high response rates for primary advanced and recurrent or resistant
      OCCA. We retrospectively reviewed the outcome of 20 OCCA patients treated with P
      CPT by the Gynecology Service at The Jikei University Hospital after initial
      surgery. These patients received a total of 101 cycles of P-CPT, with a median of
      5 cycles each. Two complete responses (CRs) were obtained in the three patients
      with measurable disease, and response duration was 7 and 15 months, respectively.
      One patient had stable disease (SD), and the time to progression was 5 months.
      The estimated 3- and 5-year survival rates were 69% and 69%, respectively. Our
      current data and previous reports suggest that P-CPT is a candidate first-line
      chemotherapy regimen for OCCA.

PMID- 18050829
TI  - Sigmoid colon cancer with mediastinal lymph node metastases.
AB  - Mediastinal lymph node metastasis from colorectal cancer is rarely seen. We
      herein report on a 74-year-old man who was hospitalized with multiple brain
      metastases and mediastinal lymph node metastasis from an adenocarcinoma of the
      sigmoid colon. A preoperative brain magnetic resonance image showed multiple
      brain tumors, and a chest computed tomography (CT) scan indicated a mediastinal
      tumor. CT-guided aspiration biopsy cytology of the mediastinal tumor showed
      metastatic adenocarcinoma from a digestive tract tumor. Barium enema and sigmoid
      colonoscopy showed that the cancer was located in the sigmoid colon. Laparoscopic
      assisted sigmoidectomy with lymph node dissection was performed. Pathological
      findings of the specimen showed a moderately differentiated adenocarcinoma that
      invaded to the subserosa, but no evidence of lymph node metastasis was found. The
      patient was discharged 3 weeks after the operation and died 3 months later.

PMID- 18050830
TI  - Case of breast cancer with endocrine differentiation.
AB  - An 89-year-old woman presented with a chief complaint of induration in the left
      breast persisting for 1 month. Core needle biopsy of the lesion showed invasive
      breast cancer. Therefore, we diagnosed the lesion as left breast cancer and
      performed a modified mastectomy. On the immunohistochemical study, the tumor was
      positive for synaptophysin and positive in part for chromogranin-A and
      carcinoembryonic antigen. Therefore, we diagnosed the lesion as breast cancer
      with endocrine differentiation. We report the clinical and pathological features
      of this disease herein.

PMID- 18050831
TI  - An unusual tumor presentation.
AB  - Germ cell cancer is the most common malignancy in men 15-35 years of age; 5% of
      malignant germ cell tumors are of extragonadal origin. The key to diagnosis and
      management is tumor histology. This point is highlighted in this case review. It
      also reinforces that germ cell tumor markers should be done in all young patients
      diagnosed with malignancy. We describe the case of a 21-year-old man who was
      diagnosed as having inoperable cancer of the ascending colon, which turned out to
      be extragonadal germ cell tumor after studies. This patient has responded very
      well to bleomycin, etoposide, and cisplatin chemotherapy.

PMID- 18050832
TI  - Appendiceal Enterobius vermicularis infestation in adults.
AB  - The objective of this study is to evaluate the incidence of Enterobius
      vermicularis in the appendices of the adult population and a possible
      relationship between E. vermicularis and acute appendicitis. E. vermicularis was
      identified in 18 (2%) of 890 patients. Six hundred sixty-five operations were
      performed for presumptive diagnosis of acute appendicitis, and E. vermicularis
      was found in 12 (2%) patients. The histopathological examination revealed acute
      inflammatory cells in four cases (33%). Three of these four specimens included
      luminal ova and one E. vermicularis. Histopathological examination of six cases
      revealed E. vermicularis in 225 incidental appendectomies with no evidence of
      either acute or chronic inflammatory cells. This study suggests a relationship
      between the presence of E. vermicularis ova and acute inflammation, but the
      presence of the pinworm in the lumen of the appendix is coincidental. On the
      other hand E. vermicularis in the appendix lumen can cause symptoms of acute
      appendicitis.

PMID- 18050833
TI  - Distant solitary skeletal muscle metastasis from papillary thyroid carcinoma.
AB  - An unusual case of isolated trapezoid muscle metastasis from a papillary
      carcinoma of the thyroid gland is described. Although extrathyroidal extension to
      the soft tissues of the neck may occur, distant metastases are rare in papillary
      thyroid carcinoma. Skeletal muscle metastasis from a differentiated thyroid
      carcinoma seems to be extremely rare, even for the follicular type of this
      cancer, well known for its hematogenous spread to various sites.

PMID- 18050834
TI  - Pancreatic metastasis from renal cell carcinoma 13 years after a nephrectomy:
      report of a case.
AB  - The pancreas is an uncommon site of metastasis from renal cell carcinoma. We
      herein present the case of a 59-year-old woman in whom pancreatic metastasis from
      renal cell carcinoma, found 13 years after undergoing a nephrectomy, was
      successfully resected and who has since showed no evidence of recurrence or
      metastasis. The efficacy of performing a pancreatectomy for metastatic renal cell
      carcinoma is also presented. We recommend careful long-term follow-up in patients
      with a history of renal cell carcinoma. Imaging modalities should be used during
      the routine follow-up to detect any asymptomatic metastases at an early stage.

PMID- 18050835
TI  - Mesorectum amputation technique for laparoscopic anterior resection.
AB  - The objective of this study was to assess our original procedure, the cutting off
      method (COM), where the rectum and mesorectum are cut off with an autosuture
      device simultaneously in laparoscopic anterior resection. From 2001 to 2003,
      laparoscopic anterior resection was performed in 21 patients at our institution
      using the COM (n = 14) and trimming method (TM; n = 7). We reviewed the medical
      records for operative duration, intraoperative blood loss, and postoperative
      complications. The operation lasted 165 minutes (range, 140-215 minutes) in the
      TM group, but only 120 minutes (range, 95-135 minutes) in the COM group (P <
      0.01). Intraoperative blood loss was 90 ml (range, 60-140 ml) in the TM group and
      30 ml (range, 5-90 ml) in the COM group (P < 0.01). There were no postoperative
      complications in the COM group, although one complication of minor leakage was
      observed in the TM group.

PMID- 18050836
TI  - Appropriate approach to bronchobiliary fistulas: a case series with hydatid
      disease and algorithm of case-based management.
AB  - Bronchobiliary fistula caused by liver echinococcosis is a relatively unusual but
      severe complication of hydatid disease. Optimal management of cases is crucially
      important in establishing rapid recovery and avoiding additional complications.
      The use of an algorithmic guide is essential because of an ongoing dilemma that
      involves a large variety of therapeutic options. We present four patients with
      bronchobiliary fistulas caused by liver hydatid disease to discuss the management
      of therapeutic options through a case-based approach and an extent review to
      finally generate an algorithm. In this series, two patients were treated
      surgically, and the remaining were treated with conservative methods. To date,
      they have developed neither recurrence nor need for additional intervention.
      Although treatment of bronchobiliary fistulas is traditionally thought to be
      surgical, most of the less severe cases can be treated nonoperatively. Making an
      accurate selection among less invasive methods and/or open surgical interventions
      seems to be a key component of management.

PMID- 18050837
TI  - Gut flora in health and small intestinal bacterial overgrowth syndrome.

PMID- 18050838
TI  - Living donor liver transplantation.
AB  - Initially living donor liver transplantation (LDLT) was almost exclusively
      performed in infants and children. Adult LDLT programmes were initiated several
      years later. In the west this programme was introduced in view of a critical
      shortage of deceased donors and a constant increase in waiting list mortality. At
      present, this procedure is accepted as a therapeutic option for patients with end
      stage liver disease to make up for the shortage of donor organs from dead
      patients. In Asia, however, LDLT has become the predominant means of liver
      transplantation as donor organs from the diseased cannot be used for religious
      and ethical reasons. Although there have been significant improvements in
      surgical techniques and consequently in recipient outcome over recent years, the
      LDLT procedure is still associated with donor morbidity and even mortality. The
      overall reported donor mortality was 0.2% and donor morbidity ranged between 0%
      and 100%. Biliary complications and infections were the most commonly reported
      donor complications. Therefore, a thorough medical as well as psychological
      evaluation of the donor and recipient are necessary prior to this procedure. To
      date, LDLT comprises less than 5% of adult liver transplantations in Europe and
      in the United States. Recipient and graft survival are almost identical to those
      seen with liver transplantations from deceased donors (DD). Biliary and vascular
      complications are more often seen in the LDLT setting. So far, no studies have
      focussed on the impact of LDLT on waiting list mortality. There is international
      consensus that this procedure should be restricted to centres with large
      experience in deceased donor liver transplantations as well as in hepatobiliary
      surgery. Ethical issues, optimal utility and application of adult LDLT and
      optimal recipient and donor characteristics have yet to be defined.

PMID- 18050839
TI  - Management of gastric variceal bleeding.

PMID- 18050840
TI  - Genotype III - HCV infection.

PMID- 18050842
TI  - Role of liver biopsy in management of chronic hepatitis B and chronic hepatitis
      C.

PMID- 18050841
TI  - Modification of small bowel microflora in chronic alcoholics with alcoholic liver
      disease.
AB  - The bacterial flora of the gastrointestinal tract plays an essential role in
      human physiology. Our aim was to study the pattern of change in bacterial
      microflora in the small intestines of patients with chronic alcoholic liver
      disease (ALD). Patients of ALD made up the test group and nonalcoholics served as
      controls. Duodenal (D2) biopsies were obtained by upper gastrointestinal
      endoscopy and processed immediately for microbiological analysis. Marked
      qualitative and quantitative alterations of small intestinal microflora was
      documented in chronic alcoholics. There was increased bacterial growth of both
      gram-positive cocci and gram-negative bacilli in the ALD group.

PMID- 18050843
TI  - Correlation between endoscopic suspicion of gastric cancer and histology in
      Nigerian patients with dyspepsia.
AB  - Gastric mucosal biopsies of 77 dyspeptic patients whose endoscopic features were
      suggestive of cancer and 56 patients with uncomplicated duodenal ulcer (DU) were
      subjected to histopathological analysis. Gastric cancer was confirmed in 18
      (23.4%) of the 77 patients but not in 59 (76.6%). 4 (5.2%) of the 18 patients had
      early gastric cancer (EGC). Histopathological findings in the stomach biopsy of
      the 59 patients in whom cancer could not be confirmed were compared with those of
      the 56 patients with DU. Intestinal metaplasia (IM) was present in 32.2% of the
      59 cases with endoscopic suspicion of gastric cancer and in 16.1% of the 56 DU
      controls (P < 0.05). Mucosa-associated lymphoid tissue (MALT) occurred in 28.8%
      of the cancer-resembling cases and in 12.5% of the DU patients (P < 0.05). The
      difference in the prevalence of gastric mucosal atrophy and Helicobacter pylori
      infection between the two groups (83% vs. 71.4%) did not reach statistical
      significance (P > 0.10). All 18 patients with gastric cancer were positive for
      Helicobacter pylori and the prevalence of the infection approached 95% in those
      with IM and MALT. This study shows that IM and MALT present with endoscopic
      appearances that resemble that of gastric cancer and that along with the latter,
      their main aetiological agent is Helicobacter pylori.

PMID- 18050844
TI  - Gall bladder carcinoid: a case report and review of literature.
AB  - Gall bladder carcinoid tumours are rare and usually lack specific symptoms. In
      most instances, they are incidentally detected after a cholecystectomy and rarely
      do they manifest with carcinoid syndrome. We report a case of gall bladder
      carcinoid in a patient who had undergone surgery for rectal carcinoid 10 years
      back. Occurrence of rectal carcinoid and gall bladder carcinoid in the same
      patient has not been reported before.

PMID- 18050845
TI  - Colonic actinomycosis masquerading as perforated colonic carcinoma.
AB  - A case of Actinomycosis affecting the transverse colon masquerading as an
      abdominal neoplasm with perforation to abdominal parietal wall is presented.
      Abdominal actinomycosis lesions may present as a perforated abdominal neoplasm
      requiring emergency laparotomy. This case report highlights the diagnostic
      dilemma and the management algorithm for such infections.

PMID- 18050846
TI  - Management of anorectal melanomas: a 10-year review.
AB  - BACKGROUND: Anorectal melanoma (AM) is a rare tumour with poor prognosis. The
      primary modality of treatment for AM is surgery. However, the choice of operation
      is controversial. Historically, radical operations like abdominoperineal excision
      of rectum (APER) with or without inguinal lymph node dissection were preferred.
      However, as no stage-specific survival advantage has been seen with APER later
      studies have recommended wide local excision (WLE) as the preferred treatment
      where negative margins can be achieved. The aim of our study was to review our
      results. METHODS: Inpatient and outpatient charts of all patients treated for AM
      between 1996 and 2005 were reviewed. Patient characteristics, clinical
      presentation, evaluation, staging, treatment, complications and followup were
      studied. Patients were followed up to assess disease free and overall survival
      according to the stage of disease and the surgical procedure performed. RESULTS:
      17 patients were treated for AM between 1996 and 2005. At presentation 4 (23%)
      had metastatic and 1 (6%) had inoperable disease. 12 patients (71%) had operative
      therapy of which 10 had APER and two had WLE. 82% of these patients were followed
      up for a mean duration of 8 months (range 3-30 months) and their overall and
      disease free survival compared. The stage specific disease free and overall
      survival for patients who underwent APER was 8 months and 13 months for stage I
      and 7 months and 10 months for stage II respectively. The disease free survival
      and overall survival for patients who underwent WLE, both for stage I disease,
      was 10 months and 27 months respectively. CONCLUSION: Despite surgical resection
      and emergence of various forms of adjuvant therapy, the overall prognosis of
      anorectal melanoma remains dismal. From a review of literature and our own
      experience, though limited, we conclude that WLE be recommended where negative
      margins can be achieved and where this is technically feasible. APER should be
      reserved for large tumours where WLE is not technically possible.

PMID- 18050847
TI  - Liver abscess, portal vein thrombosis and cavernoma formation following umbilical
      vein catherisation in two neonates.
AB  - Liver abscess is a rare condition in neonates and its diagnosis requires a high
      degree of suspicion. CT scan and ultrasound are the most sensitive diagnostic
      modalities for detecting hepatic abscess. Portal vein thrombosis and cavernoma
      formation are rare complications following neonatal liver abscess and sepsis. We
      describe the case of two neonates with hepatic abscess following umblical vein
      catheterisation, with rare complications of portal vein thrombosis and portal
      vein cavernoma formation. Therefore, unreserved caution should be exercised in
      performing umbilical cannulation in neonates due to the inherent risks involved
      with this procedure.

PMID- 18050848
TI  - Neonatal gastrointestinal mucormycosis--a case report.
AB  - Mucormycosis is a rare opportunistic fungal infection. It occurs mainly in
      immunocompromised patients and is usually fatal in children. This fungus can
      affect central nervous system, nasopharynx, lungs, skin and gastrointestinal
      tract. It invades the blood vessels and causes thrombosis, leading to infarction
      of the surrounding tissues. The diagnosis depends mainly on histopathological
      examination and demonstration of the fungus in the tissue sections, therefore a
      high index of suspicion and early exploration is required. We report a case of
      malnourished child who presented with perforation peritonitis. Investigations
      revealed very low total serum proteins and raised serum creatinine and blood urea
      levels. On exploratory laparotomy three perforations were located in the
      gastrointestinal tract. Histopathlogical examination of the perforation edge
      sections showed characteristic fungal hyphae confirming the diagnosis of
      gastrointestinal mucormycosis.

PMID- 18050849
TI  - Isolated tubercular splenic abscess in an immunocompetent child.
AB  - Splenic abscess is an uncommon entity in children, more so of tubercular etiology
      in immunocompetent patients. The few cases reported have usually revealed
      solitary abscesses in the spleen. We present a case of a 12 year-old
      immunocompetent girl who presented with fever and pain abdomen and was detected
      to have multiple tubercular abscesses in the spleen in the absence of any other
      focus of tuberculosis.

PMID- 18050850
TI  - Peritoneal penetrating pencil injury.
AB  - An 8 year old school going boy sustained an accidental peritoneal penetrating
      injury while playing with a pencil in his trouser pocket. Surgical exploration
      revealed intact intraperitoneal and retroperitoneal viscera and the pencil could
      be successfully removed. In addition to the acute injuries there are numerous
      late sequlae of pencil injuries that cause concern.

PMID- 18050851
TI  - [Socio-economic context in the Lower Iseo Lake area after World War II].
AB  - In the second part of the 20th century, the Basso Sebino Area (Northern Italy)
      underwent a transformation into an industrial context. The first factories were
      engaged in the production of textiles, clothes and pasta. This was followed by a
      major development of mechanic, plastic and rubber industry. The latter activity
      was concentrated on the production of buttons. This text describes the evolution
      of the unions'activity in order to obtain a more decent salary and better working
      conditions in all productive areas. Within this reality, the production of
      asbestos goods started in 1950 in the Colombo enterprise, run by Rinaldo Colombo,
      The latter was also the manager of the chrysotile quarry in Balangero, province
      of Torino (the biggest asbestos mine in Western Europe). Through these
      connections, asbestos was conveyed from Balangero to the Basso Sebino Area in
      such a way that most of the asbestos chain (extraction, processing of asbestos
      goods and sales) was under the control of the same firm.

PMID- 18050852
TI  - [The productive district of textile asbestos in the Lower Iseo Lake area].
AB  - In the Bergamo area of Basso Sebino (lower Lake Iseo), for decades there has been
      a large concentration of small firms (mostly family-run), specialised in the
      production of rubber gaskets. Within this production field, some companies used
      to manufacture textile asbestos exclusively or as part of their business. The
      asbestos goods were therefore marketed as they were or subsequently cut and
      transformed into gaskets. Among the 5 companies involved, "Manifattura Colombo &
      C" was the first one that started this production in the district, and the one
      that engaged the greatest number of employees (considering both the Sarnico and
      Predore factories). In the Predore factory, operating from the fifties to 1979,
      the asbestos thread production was carried out exclusively and to the complete
      technological cycle (i.e. from crashing the raw asbestos that was brought in from
      Balangero). The whole process was performed in an extremely dusty environment
      (according to the witness of former workers), expecially during the first
      production steps. In the Sarnico factory which operated from 1920 to 1993, they
      produced textile asbestos items (laces, ropes, etc.), as well as rubber and metal
      gaskets. The latter were coupled with asbestos by means of metal-plastics co
      moulding operations, in order to obtain gaskets highly resistant to exhaust
      vapours, gases, oils, solvents and so on. The environmental data available
      (referred to the 1980-1992 period), supply evidence of severe exposure in the
      first years of activity, whilst a sharp reduction in the asbestos-fiber
      concentration rate was achieved along the years, thanks mainly to the completion
      and improvement of exhaust systems installed on winding and braiding machines.
      Finally we shortly describe the work of the four other factories and in more
      detail that of the "Manifattura Sebina srl" is mentioned herein because, although
      this is a "typical" textile mill and exclusively manufacturing cotton products, a
      considerable number of cases of mesothelioma has been detected among its
      workforce. This has been attributed to the presence of asbestos insulated piping,
      to maintenance and replacement interventions on looms brake pads, and above all
      to the nearly 50 asbestos blankets that were employed in the weekly fire-fighting
      exercises, and usually leaned against the walls of departments, with no
      protection whatsoever.

PMID- 18050853
TI  - [The epidemiologic surveillance of malignant mesothelioma in the Lower Iseo Lake
      area].
AB  - Starting from an hospital observation of the mesotheliomas cluster in women
      living in a lakeside area (Iseo lake, Northern Italy), an epidemiological
      surveillance of this tumour was performed by the local occupational health
      service. This cluster wasn't notified, in spite of the relevant number of
      factories producing asbestos textile materials in this area. From 1977 to august
      2006, 45 cases of mesothelioma were detected among the workers of 3 textile
      industries located in 3 little villages: 14 cases occurred working crocidolite
      and chrysotile rope and gasket; 20 cases in a textile factory producing cotton
      garments, that was adjacent to and polluted by the farmer and were asbestos
      insulation and blankets used for fireproofing are present; 11 cases occurred
      among women working in silk factories. The mesothelioma cases occurred in the
      same period in this area, which constituted the recruitment area of the people
      working in the 3 textile plants (11 villages, about 43,000 inhabitants), are
      55.93% of which had been occupationally exposed to asbestos. Out of the dockyard
      and the asbestos-cement industries, this frequency of occupational exposed
      workers is the highest never observed in Italy. The majority of the cases (66%)
      occurred among women working in the textile factories. In a women, producing
      asbestos textile materials and suffered form peritoneal mesothelioma and pleural
      plaques, the analysis (by SEM) of asbestos fibre lung burden show 286 million
      fibres x gr. of dry tissue. Between the 42 mesothelioma cases occurring in the
      population of the 3 villages where the textile plants was located, we observed
      only one case with possible environmental exposure to asbestos: a gardener of the
      village where the manufacturing asbestos ropes and gasket plant is present. In
      the silk factories, asbestos exposure was probable because of the presence of
      asbestos insulated pipes. The female pleural mesothelioma standard incidence
      observed in this area (6.8 x 100,000, 1977-2005) is the highest never estimate in
      Italy. The epidemiological surveillance of the mesothelioma appear essential to
      identify cases unreported and allow the collection of information useful to
      understand clearly the asbestos exposure effects on health's workers and to
      estimate the tumour incidence in the population.

PMID- 18050855
TI  - [Asbestos exposure in the non-asbestos textile industry: the experience of the
      Lombardy Mesothelioma Registry].
AB  - The Lombardy Mesothelioma Registry, activated in 2000, receives more than 300
      cases per year of suspected malignant mesothelioma; the standardized (age and
      gender) incidence rate of pleural mesothelioma is 2.4/100,000 inhabitants (CI 95%
      2.0-2.7). The finding of an increasing number of cases among workers of the non
      asbestos-textile industry, classified as "unknown exposure to asbestos", upheld
      the suspect of presence of asbestos in this compartment. Specific information
      about a possible asbestos exposure were collected by technicians, maintenance
      personnel and other experts; industrial machinery utilized in the past was
      thoroughly examined; direct inspections were carried out in several workplaces
      that had not yet undergone significant changes with respect to the past. A large
      amount of asbestos had been regularly used on the ceilings and also to the walls
      of factories in order to avoid both condensation of steam and reflection of
      noise. In addition, asbestos had also been widely used to insulate water and
      steam pipes. The braking systems of most of machines also had asbestos gaskets,
      and on several looms some brakes operated continuously. The population in study
      was composed of 119 subjects, 27 males and 92 females, median age of 72 years.
      Asbestos exposure was ascribed to work in 106 cases (89%). The system devised by
      the Lombardy Registry had brought to light an occupational hazard in a
      professional area previously never believed as a source of asbestos exposure. In
      consideration of the described experience, both environmental and clinical, it
      seems reasonable to consider the non-asbestos-textile as a new department at risk
      for asbestos exposure.

PMID- 18050854
TI  - [Epidemiological surveillance of malignant mesothelioma cases in Italy: incidence
      and asbestos exposure figures by the Italian mesothelioma registry (ReNaM)].
AB  - The Study describes the epidemiological surveillance of mesothelioma cases
      carried out by the Italian mesothelioma register (ReNaM). A Regional Operating
      Centre (COR) is present in nearly all Italian regions (17 out of 20) and it
      collects malignant mesothelioma cases and investigate the modalities of asbestos
      exposure by using a structured questionnaire. The register produces malignant
      mesothelioma incidence measures and analyses of the modalities of the asbestos
      exposure. The standardized incidence rate of malignant mesothelioma in 2001 was
      2.98 (in 100,000 inhabitants) among men and 0.98 among women; a professional
      (certain, probable, possible) exposure has been detected in 67.4% of defined
      cases. In addition to the conventional sectors (shipbuilding, railways repair and
      demolition, asbestos-cement production), also textile, building, transport,
      chemical and glass industries, petroleum and sugar refineries, electricity
      production and distribution plants are getting involved. Despite the absence of
      some regions completing the national coverage and the non homogeneity in
      collecting and coding data, the epidemiological surveillance of malignant
      mesothelioma carried out by ReNaM is an important tool for the scientific
      knowledge and the prevention of asbestos-related diseases.

PMID- 18050856
TI  - [The work of the social security and welfare branch of the Trade Union supporting
      workers suffering from mesothelioma and asbestos related diseases].

PMID- 18050858
TI  - [Criminal responsibility in non pre-meditated personal injury caused by
      inhalation of asbestos].

PMID- 18050857
TI  - [Regione Lombardia 2006-2010: action plan for asbestos derived risk prevention].

PMID- 18050859
TI  - [Asbestos fibers and mesothelioma pathogenesis].

PMID- 18050860
TI  - [Mesothelioma incidence decreases parallel to asbestos exposure decrement or
      interruption: a confirmation of a dose-response relationship, with implications
      in public health].
AB  - On the basis of the available evidence, several groups of experts and
      investigators identified a dose-response relationship between exposure to
      commercial types of asbestos fibres and mesothelioma risk. The first mathematical
      model was proposed by Peto et al. It was derived from a conceptualisation of the
      multistage theory of cancer and provides an interpretation of the risk for the
      occurrence of mesothelioma in cohorts of exposed workers. In the study described
      in this paper, the author reviewed the data suggesting a decrease in
      mesotheliomas rate follosing reduction or interruption of exposure. Descriptive
      analyses and the few available long-term cohort studies indicate a decrease in
      risk. This is supported also by the fact that even the most biopersistent
      asbestos fibres are eliminated from the lungs. Indeed, a slow but effective
      reduction of risk has been demonstrated in the cohort of Wittenoom workers in
      Australia, previously exposed to crocidolite.

PMID- 18050861
TI  - [Asbestos: a long lasting tragedy. Useful considerations for a historical
      reconstruction of the most remarkable facts].
AB  - A thought back on the "epic of asbestos" scanning the fundamental steps, from the
      "discovery" of the adverse effects for the workers. A first phase, the
      "asbestosis one" concluded in Britain in the early thirties with the issue of a
      technical legislation is described. It was the first regulation shared by the
      Unions and the asbestos companies, some of which were or will then become leaders
      all over the world. The main effect of this legislation enforcement is the
      reduction of the exposure in some units of the asbestos textile industry; no
      effects were observed instead in other asbestos industrial divisions where it's
      consumption for insulations and asbestos cement increased massively. The second
      phase lasting approximately thirty years next sees together to a formidable
      diffusion of all the asbestos fibres including the crocidolite ones, advertised
      and accepted like "indispensable" for the economical and social development, an
      absolute leadership of the companies in the management of health effects
      information for the workers and therefore also those on the pulmonary
      cancerogenicity. Such selfish and aggressive leadership, receives in return from
      government, labour and consumers organizations just inertia, impotence and
      incredulity. This attitude will also continue in the third phase, beginning in
      the early sixties of the last century. The time period will be dominated by
      mesothelioma with all its new and terrible meanings, the dangerousness of
      asbestos exposure especially to the blue one even at lower levels than those
      observed in the past for other pathologies and the long latency before the
      appearance of the effects. Discussing about asbestos substitutes was out of the
      agenda, indeed just in the period where the mining and the consumption of
      asbestos touched the highest levels. The initiatives assumed in some countries
      like the auto limitation of the use of crocidolite and a more rigorous reduction
      of the occupational exposures will only turn out useful in order to lower the
      risk for asbestosis and, probably, the one for pulmonary tumour. In the United
      States, the judicial litigation for compensation between the workers and the
      companies begins. The same phenomenon will characterize also in the other
      countries industrializes the fourth phase of the epic, until our days; it is just
      in these years, and especially during the eighties, that industry starts thinking
      about the substitution of asbestos; the lively public debate will favour
      initiatives oriented to obtain economic compensation for damages caused by past
      occupational and environmental exposures. These legal actions will carry to
      bankruptcy all the asbestos companies and later to the ban of asbestos. The
      judicial debates will also uncover "confidential" information useful to better
      reconstruct the epic, to formulate more dispassionate historical judgments and to
      allow everyone on answering to more complex questions and more important than how
      much generally it was previously believed; all this should happen contextualizing
      the ages in which the scientific acquaintances on the effects of asbestos have
      been published and disproving prejudgments, able to affect some conclusions of
      the past.

PMID- 18050862
TI  - [Asbestos exposure circumstances and malignant mesothelioma casuistry of the
      Tuscan Registry: preliminary indications on the efficacy of dust control measures
      introduced during the Seventies].

PMID- 18050863
TI  - [A common professional identity].

PMID- 18050864
TI  - [What is the clinical nursing evaluation of nephrology patients in Quebec?].

PMID- 18050865
TI  - [Injections in dialysis: are you taking risks?].

PMID- 18050866
TI  - [Benefits of predialysis consultations].

PMID- 18050867
TI  - [Nursing in teledialysis].

PMID- 18050868
TI  - [What is the role of nurses in hemodialysis?].

PMID- 18050869
TI  - [Vascular access in hemodialysis].

PMID- 18050870
TI  - [Incidence of use of flexible needles on the quality of kidney dialysis].

PMID- 18050871
TI  - [Evaluation of hemostatic compression on vascular access in hemodialysis].

PMID- 18050872
TI  - [Water quality in hemodialysis].

PMID- 18050873
TI  - [Anticoagulation of extra-corporeal circuits by citrates].

PMID- 18050874
TI  - [Improving the administration of erythropoietin].

PMID- 18050875
TI  - [Deficiency of serum albumin, a factor determining hemoglobin level in the
      hemodialysis patient].

PMID- 18050876
TI  - [Balance of calcium phosphates in the eyes of patients].

PMID- 18050877
TI  - [If pain has overwhelmed me].

PMID- 18050878
TI  - [A better understanding of patient noncompliance].

PMID- 18050879
TI  - [Booklet of receipts for hemodialysis patients].

PMID- 18050880
TI  - [Peritoneal dialysis at the disposal of everyone].

PMID- 18050881
TI  - [Optimizing the results of kidney transplantation].

PMID- 18050882
TI  - Data collection important step in fight against racial, ethnic disparities.

PMID- 18050883
TI  - Physician-focused option shows savings.
AB  - CMS' first pay-for-performance initiative for physicians shows two groups earned
      performance payments for quality and cost efficiency of $7.3 million as part of
      their share of the $9.5 million savings in the first year.

PMID- 18050884
TI  - Physician support critical for DM.
AB  - A supportive physician backing a DM program can often be the difference between
      success and a lost opportunity.

PMID- 18050885
TI  - Shape from shading: new perspectives from the Polo Mint stimulus.

PMID- 18050886
TI  - Vaginal hysterectomy: dispelling the myths.

PMID- 18050887
TI  - The Sixth World Congress on Alternatives and Animal Use in the Life Sciences.

PMID- 18050888
TI  - Axonal degeneration and neuropathy target esterase.
AB  - This brief review summarizes recent observations which suggest a possible
      mechanism for organophosphate-induced delayed neuropathy (OPIDN). Neuropathy
      target esterase (NTE) has been shown to deacylate endoplasmic reticulum (ER)
      membrane phosphatidylcholine (PtdCho). Raised levels of PtdCho are present in the
      brains of Swiss cheese/NTE mutant Drosophila together with abnormal membrane
      structures, axonal and dendritic degeneration and neural cell loss. Similar
      vacuolated pathology is found in the brains of mice with brain-specific deletion
      of the NTE gene and, in old age, these mice show clinical and histopathological
      features of neuropathy resembling those in wild-type mice chronically dosed with
      tri-ortho-cresylphosphate. It is suggested that OPIDN results from the loss of
      NTE's phospholipase activity which in turn causes ER malfunction and perturbation
      of axonal transport and glial-axonal interactions.

PMID- 18050889
TI  - Surgical site infection: the host factor.
AB  - More than 30 million surgical procedures are performed annually in the United
      States, and surgical site infections (SSIs) remain a major postoperative
      complication. Although bacteria contaminate all surgical wounds, not all wounds
      become infected. In most cases, the host response eradicates the microbes. The
      patient's (ie, host's) responsiveness, therefore, is an important variable in the
      equation of factors that influence the rate of infection. Optimizing the
      patient's physiological condition can help prevent SSIs. Initiatives that show
      promise in reducing SSI rates include use of supplemental oxygen, maintenance of
      core body temperature, and rigorous management of blood sugar. Perioperative
      nurses play an important role as the patient's infection control advocate.

PMID- 18050890
TI  - High-dose-rate remote afterloaders for intraoperative radiation therapy.
AB  - Intraoperative radiation therapy (IORT) is a treatment option that directly
      irradiates a surgically exposed tumor or tumor bed while preventing radiation
      exposure of normal tissues. This article discusses the high-dose-rate
      intraoperative radiation therapy (HDR-IORT) technique by reviewing the roles of
      IORT team members, discussing needed equipment and supplies, describing quality
      assurance processes, explaining the HDR-IORT treatment delivery procedure, and
      reviewing the post-treatment phase.

PMID- 18050891
TI  - Ontologies for bioinformatics.

PMID- 18050892
TI  - Scapulothoracic dissociation: a rare but severe traumatic injury with special
      implications for HEMS decision making at the scene.

PMID- 18050893
TI  - [Finding of translocon].

PMID- 18050894
TI  - [Making attempts at humane understanding of bipolar disorders].

PMID- 18050895
TI  - [Progress in psychosocial therapy for schizophrenic patients and their families].

PMID- 18050896
TI  - [Schizophrenic patients with premorbid vulnerability to stress].

PMID- 18050898
TI  - [Disturbance in receptive prosody as a premorbid vulnerability to schizophrenia].

PMID- 18050897
TI  - [Stressful life events influence occurrence, recurrence and the course of
      schizophrenia].

PMID- 18050899
TI  - [Pathological change of brain and premorbid vulnerability to stress in patients
      with schizophrenia].

PMID- 18050900
TI  - [Premorbid stress vulnerability and genetic polymorphism of brain-derived
      neurotrophic factor].

PMID- 18050901
TI  - [Formation of premorbid stress vulnerability in schizophrenia].

PMID- 18050902
TI  - [Genetic counseling in clinical psychiatry].

PMID- 18050903
TI  - [Sleep disorders].

PMID- 18050904
TI  - The reverse proteomics for identification of tumor antigens.
AB  - The identification of tumor antigens is essential for the development of
      anticancer therapeutic vaccines and clinical diagnosis of cancer. SEREX
      (serological analysis of recombinant cDNA expression libraries) has been used to
      identify such tumor antigens by screening sera of patients with cDNA expression
      libraries. SEREX-defined antigens provide markers for the diagnosis of cancers.
      Potential diagnostic values of these SEREX-defined antigens have been evaluated.
      SEREX is also a powerful method for the development of anticancer therapeutics.
      The development of anticancer vaccines requires that tumor antigens can elicit
      antigen-specific antibodies or T lymphocytes. More than 2000 antigens have been
      discovered by SEREX. Peptides derived from some of these antigens have been
      evaluated in clinical trials. This review provides information on the application
      of SEREX for identification of tumor-associated antigens (TAA) for the
      development of cancer diagnostics and anticancer therapeutics.

PMID- 18050905
TI  - Identification of novel mitochondrial membrane protein (Cdf 3) from Arabidopsis
      thaliana and its functional analysis in a yeast system.
AB  - We screened the Arabidopsis cDNA library to identify functional suppressors of
      AtBI-1, a gene that suppresses cell death induced by Bax gene expression in
      yeast. Cdf 3 encodes a 118-amino-acid protein with a molecular mass of 25 kDa.
      This protein has two uncharacterized domains at amino acids residues 5-64 and 74
      117. In the present study, CDF3 was found to induce growth defects in yeast and
      arrested yeast growth, although the cell-growth defect was somewhat less than
      that of Bax. Its localization in the inner mitochondria was essential for
      suppression of yeast-cell proliferation. The morphological abnormality of the
      intracellular network, which is a hallmark of AtBI-1, was attenuated by Cdf 3
      expression.

PMID- 18050906
TI  - The dynamics of protein decomposition in lakes of different trophic status-
      reflections on the assessment of the real proteolytic activity in situ.
AB  - Abstract The aim of this paper is to discuss the methodology of our investigation
      of the dynamics of protein degradation and the total in situ proteolytic activity
      in meso/eutrophic, eutrophic, and hypereutrophic freshwater environments.
      Analysis of the kinetics and rates of enzymatic release of amino acids in water
      samples preserved with sodium azide allows determination of the concentrations of
      labile proteins (C(LAB)), and their half-life time (T(1/2)). Moreover, it gives
      more realistic information on resultant activity in situ (V(T(1/2))) of ecto- and
      extracellular proteases that are responsible for the biological degradation of
      these compounds. Although the results provided by the proposed method are
      generally well correlated with those obtained by classical procedures, they
      better characterize the dynamics of protein degradation processes, especially in
      eutrophic or hypereutrophic lakes. In these environments, processes of protein
      decomposition occur mainly on the particles and depend primarily on a metabolic
      activity of seston-attached bacteria. The method was tested in three lakes. The
      different degree of eutrophication of these lakes was clearly demonstrated by the
      measured real proteolytic pattern and confirmed by conventional trophic state
      determinants.

PMID- 18050907
TI  - Screening and characterization of an enzyme with beta-glucosidase activity from
      environmental DNA.
AB  - A novel beta-glucosidase gene, bglA, was isolated from uncultured soil bacteria
      and characterized. Using genomic libraries constructed from soil DNA, a gene
      encoding a protein that hydrolyzes a fluorogenic analog of cellulose, 4
      methylumbelliferyl beta-D-cellobioside (MUC), was isolated using a microtiter
      plate assay. The gene, bglA, was sequenced using a shotgun approach, and
      expressed in E. coli. The deduced 55-kDa amino acid sequence for bglA showed a
      56% identity with the family 1 glycosyl hydrolase Chloroflexus aurantiacus. Bg1A
      included two conserved family 1 glycosyl hydrolase regions. When using p
      nitrophenyl-beta-D-glucoside (pNPG) as the substrate, the maximum activity of the
      purified beta-glucosidase exhibited at pH 6.5 and 55 degrees C, and was enhanced
      in the presence of Mn2+. The Km and Vmax values for the purified enzyme with pNPG
      were 0.16 mM and 19.10 micromol/min, respectively. The purified BglA enzyme
      hydrolyzed both pNPG and p-nitrophenyl-beta-D-fucoside. The enzyme also exhibited
      substantial glycosyl hydrolase activities with natural glycosyl substrates, such
      as sophorose, cellobiose, cellotriose, cellotetraose, and cellopentaose, yet low
      hydrolytic activities with gentiobiose, salicin, and arbutin. Moreover, Bg1A was
      able to convert the major ginsenoside Rb1 into the pharmaceutically active minor
      ginsenoside Rd within 24 h.

PMID- 18050908
TI  - Cohnella panacarvi sp. nov., a xylanolytic bacterium isolated from ginseng
      cultivating soil.
AB  - A Gram-positive, aerobic, rod-shaped, nonmotile, endospore-forming bacterium,
      designated Gsoil 349T, was isolated from soil of a ginseng field and
      characterized using a polyphasic approach. Comparative analysis of 16S rRNA gene
      sequences revealed that the strain Gsoil 349T belongs to the family
      Paenibacillaceae, and the sequence showed closest similarity with Cohnella
      thermotolerans DSM 17683T (94.1%) and Cohnella hongkongensis DSM 17642T (93.6%).
      The strain showed less than 91.3% 16S rRNA gene sequence similarity with
      Paenibacillus species. In addition, the presence of MK-7 as the major menaquinone
      and anteiso-C(15:0), iso-C(16:0), and C(16:0) as major fatty acids suggested its
      affiliation to the genus Cohnella. The G+C content of the genomic DNA was 53.4
      mol%. On the basis of its phenotypic characteristics and phylogenetic
      distinctiveness, strain Gsoil 349T should be treated as a novel species within
      the genus Cohnella for which the name Cohnella panacarvi sp. nov. is proposed.
      The type strain is Gsoil 349T (=KCTC 13060T = DSM 18696T).

PMID- 18050909
TI  - Functional characterization of antagonistic fluorescent pseudomonads associated
      with rhizospheric soil of rice (Oryza sativa L.).
AB  - Antagonistic fluorescent pseudomonads isolated from rhizospheric soil of rice
      were characterized by 16S rRNA amplicon and fatty acid methyl ester (FAME)
      analyses. Antagonistic isolates were grown in the fermentation media, and
      production of antibiotics was confirmed by thin-layer chromatography (TLC) and
      high-performance liquid chromatography (HPLC). Production of fungal cell-wall
      degrading enzymes such as protease, cellulase, pectinase, and chitinase was
      determined. Dendrogram based on the major and differentiating fatty acids
      resulted into 5 clusters, viz., cluster I (P. pseudoalcaligenes group), cluster
      II (P. plecoglossicida group), cluster III (P. fluorescens group), cluster IV (P.
      aeruginosa group), and cluster V (P. putida group). Characteristic presence of
      high relative proportions of cyclopropane (17:0 CYCLO w7c) was observed in
      antagonistic bacteria. Data revealed biodiversity among antagonistic fluorescent
      pseudomonads associated with the rice rhizosphere. Results presented in this
      study will help to identify the antagonistic isolates and to determine their
      mechanisms that mediate antagonism against fungal pathogens of rice.

PMID- 18050910
TI  - Functional analysis of olfactory receptors expressed in a HEK-293 cell system by
      using cameleons.
AB  - Cameleon is a genetically engineered Ca2+ sensing molecule consisting of two
      variants of the green fluorescent protein (GFP), calmodulin and calmodulin
      binding protein, M13. HEK-293 cells stably expressing three types of cameleons,
      yellow cameleon-2, cameleon-3er, and cameleon-2nu, were constructed, and the
      expression and localization of these cameleons were confirmed by fluorescent
      imaging. Among the cameleons, the yellow cameleon-2 was selected for analyzing
      the change in Ca2+ induced by the olfactory receptor-mediated signal
      transduction, because it is localized in the cytosol and binds to cytosolic Ca2+
      ions. Cells stably expressing yellow cameleon-2 were transfected with each of the
      test olfactory receptor genes, odr-l0 and 17, and the expression of the olfactory
      receptor genes were examined using immunocytochemical methods and RT-PCR.
      Stimulating each olfactory receptor with its specific odorant caused an increase
      in the intracellular Ca2+ level, which was measured using yellow cameleon-2.
      These results demonstrate that yellow cameleon-2 can be conveniently used to
      examine the function of the olfactory receptors expressed in heterologous cells.

PMID- 18050911
TI  - Proteome analysis of Paenibacillus polymyxa E681 affected by barley.
AB  - Paenibacillus polymyxa E681 is known to be able to suppress plant diseases by
      producing antimicrobial compounds and to promote plant growth by producing
      phytohormones, and secreting diverse degrading enzymes. In spite of these
      capabilities, little is known regarding the flow of information from the
      bacterial strain to the barley roots. In an attempt to determine the flow of
      information from the bacterial strain to barley roots, the train was grown in the
      presence and absence of barley, and two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) and MALDI-TOF mass spectrometry were used. 2D-PAGE
      detected approximately 1000 spots in the cell and 1100 spots in the supernatant
      at a pH 4-10 gradient. Interestingly, about 80 spots from each sample showed
      quantitative variations. Fifty-three spots from these were analyzed by MALDI-TOF
      mass spectrometry and 28 proteins were identified. Most of the cytosolic proteins
      expressed at higher levels were found in P. polymyxa E681 cells grown in the
      presence of barley rather than in the absence of barley. Proteins detected at a
      lower level in the surpernatant of P. polymyxa E681 cells grown in the presence
      of barley were lipoprotein, glucose-6-phosphate 1-dehydrogenase, heat-shock
      protein HtpG spermidine synthase, OrfZ, ribonuclease PH, and coenzyme PQQ
      synthesis protein, and flagellar hook-associated protein 2 whereas proteins
      detected at a higher level in the surpernatant of P. polymyxa E681 cells grown in
      the presence of barley included D-alanyl-D-alanine ligase A,
      isopentenyldiphosphate delta-isomerase, ABC transporter ATP-binding protein Uup,
      lipase. Many of the proteins belonging to plant-induced stimulons are associated
      with biosynthetic metabolism and metabolites of proteins and transport. Some of
      these proteins would be expected to be induced by environmental changes resulting
      from the accumulation of plant-secreted substances.

PMID- 18050912
TI  - Relationship between genome similarity and DNA-DNA hybridization among closely
      related bacteria.
AB  - DNA-DNA hybridization has been established as an important technology in
      bacterial species taxonomy and phylogenetic analysis. In this study, we analyzed
      how the efficiency with which the genomic DNA from one species hybridizes to the
      genomic DNA of another species (DNA-DNA hybridization) in microarray analysis
      relates to the similarity between two genomes. We found that the predicted DNA
      DNA hybridization based on genome sequence similarity correlated well with the
      experimentally determined microarray hybridization. Between closely related
      strains, significant numbers of highly divergent genes (<55% identity) and/or the
      accumulation of mismatches between conserved genes lowered the DNA-DNA
      hybridization signal, and this reduced the hybridization signals to below 70% for
      even bacterial strains with over 97% 16S rRNA gene identity. In addition, our
      results also suggest that a DNA-DNA hybridization signal intensity of over 40%
      indicates that two genomes at least shared 30% conserved genes (>60% gene
      identity). This study may expand our knowledge of DNA-DNA hybridization based on
      genomic sequence similarity comparison and further provide insights for bacterial
      phylogeny analyses.

PMID- 18050913
TI  - Expression of antihypertensive peptide, His-His-Leu, as tandem repeats in
      Escherichia coli.
AB  - His-His-Leu (HHL), a tripeptide derived from a Korean soybean paste, is an
      angiotensin-I-converting enzyme (ACE) inhibitor. We report here a method of
      producing this tripeptide efficiently by expressing tandem multimers of the
      codons encoding the peptide in E. coli and purifying the HHL after hydrolysis of
      the peptide multiners. The HHL gene, tandemly multimerized to a 40-mer, was
      ligated with ubiquitin as a fusion gene (UH40). UH40 was inserted into vector
      pET29b; the UH40 fusion protein was then produced in E. coli BL21. The
      recombinant UH40 protein was purified by cation-exchange chromatography with a
      yield of 17.3 mg/l and analyzed by matrix-assisted laser desorption ionization
      (MALDI) time-of-flight (TOF) mass spectrometry and protein N-terminal sequencing.
      Leucine aminopeptidase was used to cleave a 405-Da HHL monomer from the UH40
      fusion protein and the peptide was purified using reverse-phase high-performance
      liquid chromatography (HPLC) on a C18 HPLC column, with a final yield of 6.2
      mg/l. The resulting peptide was confirmed to be HHL with the aid of MALDI-TOF
      mass spectrometry, glutamine-TOF mass spectrometry, N-terminal sequencing, and
      measurement of ACE inhibiting activity. These results suggest that our production
      method is useful for obtaining a large quantity of recombinant HHL for functional
      antihypertensive peptide studies.

PMID- 18050914
TI  - Simultaneous and sequential co-immobilization of glucose oxidase and catalase
      onto florisil.
AB  - The co-immobilization of Aspergillus niger glucose oxidase (GOD) with bovine
      liver catalase (CAT) onto florisil (magnesium silicate-based porous carrier) was
      investigated to improve the catalytic efficiency of GOD against H2O2
      inactivation. The effect of the amount of bound CAT on the GOD activity was also
      studied for 12 different initial combinations of GOD and CAT, using simultaneous
      and sequential coupling. The sequentially co-immobilized GOD-CAT showed a higher
      efficiency than the simultaneously co-immobilized GOD-CAT in terms of the GOD
      activity and economic costs. The highest activity was shown by the sequentially
      co-immobilized GOD-CAT when the initial amounts of GOD and CAT were 10 mg and 5
      mg per gram of carrier. The optimum pH, buffer concentration, and temperature for
      GOD activity for the same co-immobilized GOD-CAT sample were then determined as
      pH 6.5, 50 mM, and 30 degrees C, respectively. When compared with the
      individually immobilized GOD, the catalytic activity of the co-immobilized GOD
      CAT was 70% higher, plus the reusability was more than two-fold. The storage
      stability of the co-immobilized GOD-CAT was also found to be higher than that of
      the free form at both 5 degrees C and 25 degrees C. The increased GOD activity
      and reusability resulting from the co-immobilization process may have been due to
      CAT protecting GOD from inactivation by H2O2 and supplying additional O2 to the
      reaction system.

PMID- 18050915
TI  - Identification of two entomopathogenic bacteria from a nematode pathogenic to the
      Oriental beetle, Blitopertha orientalis.
AB  - A pathogenic nematode, Butlerius sp., was isolated from Oriental beetle,
      Blitopertha orientalis. The infective juveniles exhibited dose- as well as time
      dependent entomopathogenicity on the larvae of B. orientalis. Two bacterial
      species, Providencia vermicola (KACC 91278) and Flavobacterium sp. (KACC 91279),
      were isolated from the infective juveniles and identified. P. vermicola
      outnumbered Flavobacterium sp. in the nematode host, in which the colony density
      of P. vermicola was found to be 21 times higher than that of Flavobacterium sp.
      However, when the two bacterial species were cocultured in culture media without
      the nematode host, they showed similar growth rates. Both bacteria induced
      significant entomopathogenicity against Spodoptera exigua larvae infesting
      economically important vegetable crops, where P. vermicola was more potent than
      Flavobacterium sp.

PMID- 18050916
TI  - Physicochemical properties of the exopolysaccharides produced by marine bacterium
      Zoogloea sp. KCCM10036.
AB  - The physicochemical properties of the exopolysaccharide (EPS) produced by marine
      bacterium Zoogloea sp. KCCM10036 were investigated. Two types of isolated EPSs
      were shown to have average relative molecular masses (Mr) of 4.07 x 10(6) of CBP
      (cell-bound polysaccharide) and 3.43 x 10(6) of WSP (water-soluble
      polysaccharide), respectively. When the CBP was utilized as an emulsifier, it
      stabilized the emulsion for up to 148 h. Compared with other commercially
      available hydrocolloids such as xanthan gum, the Tween series, and Triton, the
      CBP showed much better emulsifying capability on a water-in-oil system. Phase
      separation occurred in the Tween series after 24 h, whereas the emulsion was
      better stabilized by the CBP. The CBP thus has potential as an emulsifying agent
      in commercial emulsions. The flocculating activity was also greatest at 0.01%
      (w/v) and decreased at higher concentrations than the optimized concentration of
      the WSP and CBP. The results also showed that both types of exopolysaccharides
      from Zoogloea sp. had excellent flocculating activity.

PMID- 18050917
TI  - Diversity of halophilic archaea from six hypersaline environments in Turkey.
AB  - The diversity of archaeal strains from six hypersaline environments in Turkey was
      analyzed by comparing their phenotypic characteristics and 16S rDNA sequences.
      Thirty-three isolates were characterized in terms of their phenotypic properties
      including morphological and biochemical characteristics, susceptibility to
      different antibiotics, and total lipid and plasmid contents, and finally compared
      by 16S rDNA gene sequences. The results showed that all isolates belong to the
      family Halobacteriaceae. Phylogenetic analyses using approximately 1,388 bp
      comparisions of 16S rDNA sequences demonstrated that all isolates clustered
      closely to species belonging to 9 genera, namely Halorubrum (8 isolates),
      Natrinema (5 isolates), Haloarcula (4 isolates), Natronococcus (4 isolates),
      Natrialba (4 isolates), Haloferax (3 isolates), Haloterrigena (3 isolates),
      Halalkalicoccus (1 isolate), and Halomicrobium (1 isolate). The results revealed
      a high diversity among the isolated halophilic strains and indicated that some of
      these strains constitute new taxa of extremely halophilic archaea.

PMID- 18050918
TI  - Optimized serological isolation of lung-cancer-associated antigens from a yeast
      surface-expressed cDNA library.
AB  - The technique of serological analysis of antigens by recombinant cDNA expression
      library (SEREX) uses autologous patient sera as a screening probe to isolate
      tumor-associated antigens for various tumor types. Isolation of tumor-associated
      antigens that are specifically reactive with patient sera, but not with normal
      sera, is important to avoid false-positive and autoimmunogenic antigens for the
      cancer immunotherapy. Here, we describe a selection methodology to isolate
      patient sera-specific antigens from a yeast surface-expressed cDNA library
      constructed from 15 patient lung tissues with non-small cell lung cancer (NSCLC).
      Several rounds of positive selection using patient sera alone as a screening
      probe isolated clones exhibiting comparable reactivity with both patient and
      normal sera. However, the combination of negative selection with allogeneic
      normal sera to remove antigens reactive with normal sera and subsequent positive
      selection with patient sera efficiently enriched patient sera-specific antigens.
      Using the selection methodology described here, we isolated 3 known and 5 unknown
      proteins, which have not been isolated previously, but and potentially associated
      with NSCLC.

PMID- 18050919
TI  - Development of homogeneous enzyme immunoassay for the organophosphorus
      insecticide fenthion.
AB  - A rapid, convenient homogeneous competitive enzyme immunoassay for estimating the
      amount of fenthion is described. The assay utilizes glucose-6-phosphate
      dehydrogenase-hapten conjugates that are inhibited in solution by antibodies
      obtained from bovine serum albumin-hapten conjugates. In order to investigate the
      effects of bridging group recognition on the sensitivity of dose response
      characteristics, the bridging groups of varying alkyl chain length were attached
      at the phosphate position of fenthion. Among the antibodies used, the one
      obtained from the use of hapten (fenthion analog) with the same bridging group
      structure that was used in preparing the enzyme-fenthion conjugates showed
      maximum inhibition (up to 51.8%) in the absence of fenthion. In the presence of
      fenthion, the activity of the enzyme-hapten conjugate is regained in an amount
      proportional to the fenthion concentration. Under the optimized condition, the
      ED50 value for fenthion was 0.809 microg/ml. The assay developed in this study is
      a rapid effective screening method for fenthion prior to precise analysis.

PMID- 18050920
TI  - Biochemical analysis on the parallel pathways of methionine biosynthesis in
      Corynebacterium glutamicum.
AB  - Two alternative pathways for methionine biosynthesis are known in Corynebacterium
      glutamicum: one involving transsulfuration (mediated by metB and metC) and the
      other involving direct sulthydrylation (mediated by metY). In this study, MetB
      (cystathionine gamma-synthase) and MetY (O-acetylhomoserine sulfhydrylase) from
      C. glutamicum were purified to homogeneity and the biochemical parameters were
      compared to assess the functional and evolutionary importance of each pathway.
      The molecular masses of the native MetB and MetY proteins were measured to be
      approximately 170 and 280 kDa, respectively, showing that MetB was a homotetramer
      of 40-kDa subunits and MetY was a homohexamer of 45-kDa subunits. The Km values
      for the O-acetylhomoserine catalysis effected by MetB and MetY were 3.9 and 6.4
      mM, and the maximum catalysis rates were 7.4 (kcat = 21 s(-1)) and 6.0 (kcat=28
      s(-1)) micromol mg(-1) min(-1), respectively. This suggests that both MetB and
      MetY can be comparably active in vivo. Nevertheless, the Km value for sulfide
      ions by MetY was 8.6 mM, which was too high, considering the physiological
      condition. Moreover, MetB was active at a broad range of temperatures (30 and 65
      degrees C) and pH (6.5 and 10.0), as compared with MetY, which was active in a
      range from 30 to 45 degrees C and at pH values from 7.0 to 8.5. In addition, MetY
      was inhibited by methionine, but MetB was not. These biochemical data may provide
      insight on the role of the parallel pathways of methionine biosynthesis in C.
      glutamicum with regard to cell physiology and evolution.

PMID- 18050921
TI  - Cloning of fibrinolytic enzyme gene from Bacillus subtilis isolated from
      Cheonggukjang and its expression in protease-deficient Bacillus subtilis strains.
AB  - Bacillus subtilis CH3-5 was isolated from cheonggukjang prepared according to
      traditional methods. CH3-5 secreted at least four different fibrinolytic
      proteases (63, 47, 29, and 20 kDa) into the culture medium. A fibrinolytic enzyme
      gene, aprE2, encoding a 29 kDa enzyme was cloned from the genomic DNA of CH3-5,
      and the DNA sequence determined. aprE2 was overexpressed in heterologous B.
      subtilis strains deficient in extracellular proteases using a E. coli-Bacillus
      shuttle vector. A 29 kDa AprE2 band was observed and AprE2 seemed to exhibit
      higher activities towards fibrin rather than casein.

PMID- 18050922
TI  - Human apolipoprotein E2 transgenic mice show lipid accumulation in retinal
      pigment epithelium and altered expression of VEGF and bFGF in the eyes.
AB  - We investigated the human apolipoprotein E2 (apoE2) transgenic mouse as an animal
      model system for age-related macular degeneration (AMD). Transgenic mice
      expressing human apoE2 and C57BL/6J mice were fed normal chow or a high-fat diet
      for 4 weeks. Eyes were collected from the mice and lipid deposits in retinal
      pigment epithelium (RPE) were assessed using electron microscopy. The expressions
      of apoE, vascular endothelial growth factor (VEGF), basic fibroblast growth
      factor (bFGF), and pigment-epithelium derived factor (PEDF), which are molecular
      markers for angiogenesis, were assessed with immunohistochemistry. Eyes from
      apoE2 mice, regardless of diet, contained lipid accumulation in RPE under
      electron microscopy, whereas control C57BL/6J eyes did not. Lipid accumulation
      was found predominantly in the RPE and the Bruch's membrane and increased in the
      eyes of apoE2 mice after one month of a high-fat diet (8 +/- 2 per 50 microm2 for
      normal chow and 11 +/- 2 per 50 microm2, p < 0.05). ApoE expression was similar
      in the apoE2 and control mice; however, VEGF and bFGF were overexpressed in the
      retinal pigment epithelium of apoE2 eyes compared with control eyes, and PEDF
      expression was slightly decreased. These expression patterns of VEGF, bFGF, and
      PEDF suggest angiogenesis is progressing in apoE2 eyes. In conclusion, the eyes
      of apoE2 mice develop typical lipid accumulations, a common characteristic of
      AMD, making them a suitable animal model for AMD. The expression profile of VEGF
      and bFGF on the retinal pigment epithelium suggests that apoE2 may induce
      neovascularization by altering angiogenic cytokines.

PMID- 18050923
TI  - Double-enhancement strategy: A practical approach to a femto-molar level
      detection of prostate specific antigen-alpha1-antichymotrypsin (PSA/ACT complex)
      for SPR immunosensing.
AB  - Prostate specific antigen-alpha1-antichymotrypsin was detected by a double
      enhancement strategy involving the exploitation of both colloidal gold
      nanoparticles (AuNPs) and precipitation of an insoluble product formed by HRP
      biocatalyzed oxidation. The AuNPs were synthesized and conjugated with horse
      radish peroxidase-PSA polyclonal antibody by physisorption. Using the protein
      colloid for SPR-based detection of the PSA/ACT complex showed their enhancement
      as being consistent with other previous studies with regard to AuNPs enhancement,
      while the enzyme precipitation using DAB substrate was applied for the first time
      and greatly amplified the signal. The limit of detection was found at as low as
      0.027 ng/ml of the PSA/ACT complex (or 300 fM), which is much higher than that of
      previous reports. This study indicates another way to enhance SPR measurement,
      and it is generally applicable to other SPR-based immunoassays.

PMID- 18050924
TI  - Correlation between enhancing effect of sodium butyrate on specific productivity
      and mRNA transcription level in recombinant Chinese hamster ovary cells producing
      antibody.
AB  - Sodium butyrate (NaBu) has been used to enhance protein expression levels in
      mammalian cell culture. To determine the clonal variability of recombinant
      Chinese hamster ovary (rCHO) cells in response to NaBu addition regarding
      specific antibody productivity (q(Ab)), three rCHO clones were subjected to
      different concentrations of NaBu. For all three clones, NaBu addition inhibited
      cell growth and decreased cell viability in a dose-dependent manner. On the other
      hand, the enhancing effect of NaBu on q(Ab) varied significantly among the
      clones. NaBu addition enhanced the antibody production of only one clone. RT-PCR
      analysis revealed that the changes in q(Ab) correlated linearly with those of the
      mRNA transcription level. Thus, it was concluded that the different enhancing
      effects of NaBu on protein expression in rCHO cell clones resulted from their
      different mRNA transcription levels.

PMID- 18050925
TI  - Genetic variability and phylogenetic relationship among proton-beam-irradiated
      strains of Pleurotus ostreatus.
AB  - To assess the effects of a proton beam on oyster mushrooms (Pleurotus ostreatus),
      the genetic diversity and phylogenetic relationships among strains induced by a
      proton beam were investigated based on a clustering analysis. According to an
      AFLP DNA polymorphism analysis, the induced strains were divided into four groups
      that coincided with the dose. When applying proton-beam radiation, the
      dissimilarity among the induced strains increased when increasing the dose. When
      using more than 400 Gy, the genetic dissimilarity of the irradiated strains was
      46-58%. Thus, evaluating the induced strains using the AFLP technique was
      effective in revealing the mutation effect of the proton beam.

PMID- 18050926
TI  - Increase of CoQ10 production level by the coexpression of decaprenyl Diphosphate
      synthase and 1-deoxy-D-xylulose 5-phosphate synthase isolated from Rhizobium
      radiobacter ATCC 4718 in recombinant Escherichia coli.

PMID- 18050927
TI  - Optimization of tannase production by Aureobasidium pullulans DBS66.
AB  - Tannase production by Aureobasidium pullulans DBS66 was optimized. The organism
      produced maximum tannase in the presence of 1% tannic acid after 36 h. Maximum
      gallic acid accumulation was observed within 36 h and tannic acid in the
      fermented broth was completely degraded after 42 h of growth. Glucose had a
      stimulatory effect on tannase synthesis at 0.1% (w/v) concentration. The organism
      showed maximum tannase production with (NH4)2HPO4 as nitrogen source. Shaking
      speed of 120 rpm and 50-ml broth volume have been found to be suitable for
      maximum tannase production.

PMID- 18050928
TI  - New finding and optimal production of a novel extracellular alkaline lipase from
      Yarrowia lipolytica NRRL Y-2178.
AB  - Lipases are industrially useful versatile enzymes that catalyze numerous
      different reactions including hydrolysis of triglycerides, transesterification,
      and chiral synthesis of esters under natural conditions. Although lipases from
      various sources have been widely used in industrial applications, such as in
      food, chemical, pharmaceutical, and detergent industries, there are still
      substantial current interests in developing new microbial lipases, specifically
      those functioning in abnormal conditions. We screened 17 lipase-producing yeast
      strains, which were prescreened for substrate specificity of lipase from more
      than 500 yeast strains from the Agricultural Research Service Culture Collection
      (Peoria, IL, U.S.A.), and selected Yarrowia lipolytica NRRL Y-2178 as a best
      lipase producer. This report presents new finding and optimal production of a
      novel extracellular alkaline lipase from Y. lipolytica NRRL Y-2178. Optimal c
      ulture conditions f orlipase production by Y. lipolytica NRRL Y-2178 were 72 h
      incubation time, 27.5 degrees C, pH 9.0. Glycerol and glucose were efficiently
      used as the most efficient carbon sources, and a combination of yeast extract and
      peptone was a good nitrogen source for lipase production by Y. lipolytica NRRL Y
      2178. These results suggested that Y. lipolytica NRRL Y-2178 showsgood industrial
      potential as a new alkaline lipase producer.

PMID- 18050929
TI  - [Understanding left ventricular hypertrophy].

PMID- 18050930
TI  - [Morphometric and morphologic studies in right ventricular hypoplasia].
AB  - In hypoplastic right ventricle the dysplasia of the tricuspid valve (TV) has
      repercussions on the development of the right ventricle. This paper documents the
      results of an anatomopathologic and morphometric studies of the tricuspid valve
      and the right ventricle in 25 hearts with this cardiopathy, which were
      morphologically analyzed using the segmentary sequential system. The following
      measurements were made: the annulus of the tricuspid valve, the thickness of the
      walls of the right ventricle, the ventricular septum and the distances from the
      atrioventricular-apex (AV-A) and from the apex-pulmonary valve (A-PV). The values
      obtained were compared with those of normal hearts of equivalent ages; the
      morphologic features of the tricuspid valve and the right ventricle were
      described. The thickness of the anterior and posterior walls of righ ventricle
      was between 2 and 10 times greater than normal. The tickness of the ventricular
      septum was 1 to 3 times greater than normal and the anterior wall of the
      infundibulum from 1 to 4 times greater than normal; the AV-A and A-PV distances
      were reduced in a half of the normal length. The great reduction of the right
      ventricular cavity was found to be related to the great hypertrophy of the right
      ventricular walls. The TV was dysplastic with Ebstein's anomaly (72%). The size
      of the tricuspid valve was small and it was a good indicator for the size of the
      right ventricle. Morphometric studies are useful because they quantitatively
      document alterations in the dimensions of valves, walls and diameters of the
      cardiac chambers in congenital heart disease.

PMID- 18050931
TI  - Predictors of mortality and adverse outcome in elderly high-risk patients
      undergoing percutaneous coronary intervention.
AB  - OBJECTIVES: We sought to identify predictors of in-hospital and long-term (> 1
      year) mortality and major adverse cardiac events (MACE) in elderly patients
      referred for percutaneous coronary intervention (PCI). METHODS: Seventy-three
      patients (> or = 80 years) were included. Clinical and interventional
      characteristics were collected retrospectively. Primary end points were in
      hospital and long-term mortality, and a composite of non-fatal myocardial
      infarction, target vessel revascularization, urgent coronary artery bypass graft
      surgery, and death (MACE). RESULTS: Eighty-three percent of the patients had
      acute coronary syndromes, 43% three-vessel disease, and 42% heart failure. In
      hospital mortality and MACE were 16.4% and 19%, respectively. Long-term mortality
      and MACE were 11.3% and 16.4%, respectively. Univariate characteristics
      associated with in-hospital mortality and MACE were: Killip Class III-IV, heart
      failure, cardiogenic shock, TIMI 0-2 flow prior and after intervention, diabetes
      mellitus, contrast nephropathy, and presence of A-V block or atrial fibrillation
      (AF). Long term predictors for mortality were the presence of heart failure,
      cardiogenic shock, diabetes mellitus, TIMI flow 0-2 before and after
      intervention, and A-V block or AF. CONCLUSION: The identification of the factors
      previously mentioned may help to predict complications in elderly patients.

PMID- 18050932
TI  - [Endomyocardial biopsy. Revision and experience of 176 procedures].
AB  - Endomyocardial biopsy (EB) is often used in the clinical evaluation of several
      cardiac disease. Hundred-seventy-six consecutive procedures were performed in 65
      patients, 43 men and 22 women mean age was 29.86 +/- 11.53 (range 4 days to 66
      years). Group A, 26 postcardiac transplantation patients in whom 137 EB were
      performed (39 heterotopic and 98 orthotopic), average sample 5.2 biopsy for each
      patient. Group B (n = 39) was studied for several cardiac diseases during cardiac
      diagnostic catheterism. The jugular venous approach was performed in 3 patients
      (1.7%), femoral in 173 patients. Major complications were found in 3 (1.7%) cases
      consisting in cerebrovascular accident (stroke) and coronary fistula into the
      right ventricle. Endomyocardial biopsy provides a low incidence of adverse
      reactions, mortality was 0%.

PMID- 18050933
TI  - [Tuberculous pericarditis. Ten years experience].
AB  - We review the clinical files of patients who entered the Regional General
      Hospital No. 20 IMSS in the City of Tijuana Mexico between May 1994 and May 2004
      with diagnosis of primary acute pericardial disease. Patients diagnosed as having
      active tuberculous pericardial effusion were eligible for the study. Twenty-one
      were included in the study (14 men and 7 women). The aged ranged from 16 to 48
      years (mean 36 years). The diagnosis was made by the following studies:
      identification of tubercle bacilli in the pericardial fluid or tissue (n = 4),
      identification of caseating granulomas in the pericardium or elsewhere (n = 2),
      positive culture for Mycobacterium tuberculosis in pericardial fluid (n = 8), in
      pleural fluid (n = 1), sputum culture (n = 3), gastric aspirate samples (n = 1),
      lymph node biopsy (n = 1), and pericardial effusion without obvious cause,
      responding to antituberculous therapy (n = 5). The clinical, laboratory,
      electrocardiography, radiographic, and echocardiography features were analyzed.
      We review in each patient follow-up, pericardial fluid cytology, and pericardial
      biopsy, if available. All patients had pericardial effusion; nine (42.8%)
      patients had cardiac tamponade. Pericardiocentesis was performed in 16 patients,
      "therapeutic" pericardiocentesis was performed in 43.7%, and "diagnostic"
      pericardiocentesis was performed in 56.2% all cases. Constrictive pericarditis
      developed in two patients, all required partial pericardiectomy. All patients
      received triple antituberculous chemotherapy. No patient died.

PMID- 18050934
TI  - [Balloon angioplasty for native aortic coarctation in children younger than 12
      months: immediate and medium-term results].
AB  - INTRODUCTION AND OBJECTIVES: The use of the balloon angioplasty (BA) in the
      treatment of patients with native aortic coarctation during childhood,
      particularly during the first 12 months of age, is controversial. The aim of this
      study was to report our experience with the use of this therapeutic technique and
      review the immediate and middle-term results in patients until 12 months age with
      native aortic coarctation and to identify those factors related with the outcome.
      MATERIAL AND METHOD: We review retrospectively the clinical records of 35
      patients less than 12 months of age with diagnosis of native aortic coarctation
      who underwent balloon angioplasty as first choice treatment during an eight year
      span (1998-2005). Total population was divided in two groups: group A patients <
      or = 3 months of age (n = 19) and group B patients between 4-12 months of age (n
      = 16). RESULTS: Mean age at the time of balloon angioplasty was 4.3 +/- 3.3
      months (range 0.7-12 months) and the mean body weight was 5.5 +/- 1.7 kg (range
      2.6-10 kg). Initial result after BA was successful in 30 of 35 patients (85.8%)
      with a peak residual pressure gradient < or = 20 mm Hg. Successful result were
      obtained in 15 of 19 patients in group A (78.9%) and in 15 of 16 patients in
      group B (93.8%). The mean peak residual pressure gradient change from 46.9 +/-
      20.3 mm Hg to 11.6 +/- 8.1 mmHg (p < 0.001) and the maximal coarctation diameter
      increase from 3.0 +/- 1.6 mm to 6.0 +/- 1.8 mm after BA in the group total. We
      did not observe deaths related to the procedure. On the follow-up recoarctation
      was observed in 17/35 patients (48.6%) 13 of them in group A (68.4%) and 4 in
      group B (25%). Ten patients with recoarctation underwent immediate surgical
      correction (9 in group A) while the other 7 underwent a second BA procedure (4 in
      group A). At the end of the study period AB was effective in 23 of 35 patients
      (65.7%), 9 of them in group A (47.3%) and 14 in group B (87.5%). The incidence of
      complications following BA was higher in group A (21%) than for group B (12.5%).
      Incidence of aneurysms was 15.8% for group A and 18.8% for group B (3 patients in
      each group). CONCLUSIONS: Balloon angioplasty is a safe and effective alternative
      treatment for native aortic coarctation, even during the neonatal period. Due to
      the high incidence of aneurysm formation in children less than 1 year of age, a
      better selection of patients, the use of low-profile balloons and optimal
      postoperative care is mandatory to improve the final outcome and decrease the
      incidence of complications. A second balloon angioplasty procedure might improve
      the final outcome.

PMID- 18050935
TI  - [Coronary artery disease in Mexican women].
AB  - OBJECTIVE: To identify differences between both genders regarding coronary artery
      disease occurrence. PATIENTS AND METHODS: In referred patients for cardiac
      catheterization we investigated coronary risk factors, clinical diagnosis,
      associated diseases, left ventricle ejection fraction, and coronary lesions. Data
      were analyzed by X2 test, Student t test, odds ratio and confidence intervals, a
      p value < 0.05 was considered significant. RESULTS: We studied 586 patients, 409
      were men. Women were older than men (59.43 +/- 9.93 vs 56.80 +/- 10.14 years old,
      p < 0.05). The frequency of coronary lesions in women was 56 vs 81% in men. The
      proportions of positive nuclear medicine studies (14 vs 16%) and exercise
      treadmill test (36 vs 28%) were similar. Acute myocardial infarction was the most
      frequent diagnosis in men (46%) whereas in women it was angor pectoris (57%).
      Smoking was observed more in men (72 vs 26%) and systemic arterial hypertension
      in women (65 vs 48%), There were no differences in diabetes mellitus and
      dyslipidemia frequencies. CONCLUSION: Systemic arterial hypertension was the risk
      factor more frequent in women, where as in men it was smoking. Ischemia induction
      tests are less specific to identify coronary atherosclerosis in women. In spite
      of the clinical data, image and laboratory results, we had a great proportion of
      women without coronary lesions.

PMID- 18050936
TI  - [Left juxtaposition of the heart atrial appendages].
AB  - We present the first case of left juxtaposition of the right atrial appendages
      that has been seen at the Children's Hospital of the state of Sonora. This
      anomaly was associated with a complex congenital heart defect, i.e. absence of
      the right atrioventricular connection and transposition of the great arteries.
      The two-dimensional echocardiogram is the usual study to reach a clinical
      diagnoses, but it may also be an incidental of finding during surgery or during
      autopsy, in ocurred in our case. Its timely diagnosis may have implications in
      the surgical treatment and in therapeutic cardiac catheterization.

PMID- 18050937
TI  - [Paradigms and paradoxes of left ventricular hypertrophy: from the research
      laboratory to the clinical consultation].
AB  - Cardiac hypertrophy can occur as an adaptative response to increased cardiac
      workload. Different types of cardiac hypertrophy arise from a combination of
      genetic, physiologic, and environmental factors. When hypertophic growth of the
      heart leads to left ventricular dysfunction and heart failure, the response is
      considered as maladaptive or pathological hypertrophy. After analyzed left
      ventricular functional and structural changes in rats induced by arterial
      hypertension, banding of aortic root, isoproterenol administration, or myocardial
      infarction, as well as in patients with arterial hypertension, aortic stenosis,
      or hypertrophic miocardiopathy, we found a maladaptive response considered as
      pathological hypertrophy. However, the adaptation of the left ventricle, found in
      response to physical activity or to pregnancy in humans, seems to help the heart
      adapt to the increase in workload acting as physiological hypertrophy. These
      considerations allow us to speculate for the use of future interventions to
      stimulate the development of physiological hypertrophy in several pathological
      situations or to change a pathological into a physiological response.

PMID- 18050938
TI  - [Electro-histological comparison in a case of Chagasic chronic cardiomyopathy].
AB  - The case of a 50 years old man, coming from an endemic Chagas' disease zone, is
      reported. This patient came with a dilated cardiomyopathy, likely of Chagasic
      etiology, and heart failure. He died in our Institute, were it was possible to
      register an ECG, and perform the necropsy, on the same day of his death. The ECG
      showed signs of heart chambers dilatation, inactive myocardium in subendocardial
      anterolateral regions of the left ventricle, and extensive subepicardial injury.
      The anatomical study demonstrated the four heart chambers dilatation, and a
      subendocardial fibrosis essentially located in anterolateral portions of the left
      ventricle. The histological examination proved that the distribution of injured
      zones corresponded to location of the inflammatory foci. Furthermore, Trypanosoma
      cruzi inoculation in mice produced inflammatory foci, predominantly located in
      the ventricular epicardial and subepicardial regions.

PMID- 18050939
TI  - Oxygenase-based whole-cell biocatalysis in organic synthesis.

PMID- 18050940
TI  - Agricultural fertilizers as economical alternative for cultivation of
      Haematococcus pluvialis.
AB  - A Haematococcus pluvialis strain isolated from the ruins of Ephesus in Turkey was
      investigated as regards its adaptation to laboratory conditions and maximum
      growth rate. In the first stage of the experiment, the growth of H. pluvialis was
      compared in common culture media. Furthermore, in an effort to minimize the
      culture costs, the second stage of the experiment compared the growth rate in the
      culture medium selected in the first stage with that in commercial plant
      fertilizers. The results demonstrated that the maximum cell concentration of 0.90
      g/l, corresponding to a growth rate of 0.150 d(-1), was found with an N-P-K
      20:20:20 fertilizer under a light intensity of 75 micromol photons m(-2) s(-1) on
      the 12th day of cultivation.

PMID- 18050941
TI  - Effect of a 20 kHz sawtooth magnetic field exposure on the estrous cycle in mice.
AB  - Female mice post weaning were exposed to 20 kHz sawtooth electric and magnetic
      fields (EMF) with 6.25 microT peak intensity for 6 weeks. Estrous cycles were
      checked using vaginal smears over the last 10 days of the experimental period.
      The vaginal smears from EMF-exposed mice revealed an increase in the frequency of
      one or two phases persisting. The number of estrous cycles less than 1 was more
      in the EMF-exposed group than in the sham control group. Furthermore, in the EMF
      exposed group, the duration of proestrous and metestrous stages of the estrous
      cycle was significantly increased compared with the control group. In conclusion,
      our results suggest that exposure to 20 kHz sawtooth EMF may affect normal
      cycling of the estrous cycle by disrupting the female reproductive endocrine
      physiology. We should not disregard the possible adverse reproductive effect of
      the 20 kHz sawtooth EMF generated under the occupational exposure situation in
      females.

PMID- 18050942
TI  - Biosynthesis of bile acids in a variety of marine bacterial taxa.
AB  - Several marine bacterial strains, which were isolated from seawater off the
      island Dokdo, Korea, were screened to find new bioactive compounds such as
      antibiotics. Among them, Donghaeana dokdonensis strain DSW-6 was found to produce
      antibacterial agents, and the agents were then purified and analyzed by LC-MS/MS
      and 1D- and 2D-NMR spectrometries. The bioactive compounds were successfully
      identified as cholic acid and glycine-conjugated glycocholic acid, the 7alpha
      dehydroxylated derivatives (deoxycholic acid and glycodeoxycholic acid) of which
      were also detected in relatively small amounts. Other masine isolates,
      taxonomically different from DSW-6, were also able to produce the compounds in a
      quite different production ratio from DSW-6. As far as we are aware of, these
      bile acids are produced by specific members of the genus Streptomyces and
      Myroides, and thought to be general secondary metabolites produced by a variety
      of bacterial taxa that are widely distributed in the sea.

PMID- 18050943
TI  - Gene cloning, expression, and functional characterization of an ornithine
      decarboxylase protein from Serratia liquefaciens IFI65.
AB  - Putrescine has a negative effect on health and is also used as an indicator of
      quality on meat products. We investigated the genes involved in putrescine
      production by Serratia liquefaciens IFI65 isolated from a spoiled Spanish dry
      cured ham. We report here the genetic organization of its ornithine decarboxylase
      encoding region. The 5506-bp DNA region showed the presence of three complete and
      two partial open reading frames. Putative functions have been assigned to several
      gene products by sequence comparison with proteins included in the databases. The
      second gene putatively coded for an ornithine decarboxylase. The functionality of
      this decarboxylase has been experimentally demonstrated by complementation to an
      E. coli defective mutant. Based on sequence comparisons of some enterobacterial
      ornithine decarboxylase regions, we have elaborated a hypothetical pathway for
      the acquisition of putrescine biosynthetic genes in some Enterobacteriaceae
      strains.

PMID- 18050944
TI  - Influence of CO2 on growth and hydrocarbon production in Botryococcus braunii.
AB  - Botryococcus braunii is a green colonial fresh water microalga and it is
      recognized as one of the renewable resources for production of liquid
      hydrocarbons. CFTRI-Bb-1 and CFTRI-Bb-2 have been reported for the first time and
      their performance with regard to growth and biochemical profile is presented
      here. The present study focused on effect of carbon dioxide (CO2) on biomass,
      hydrocarbon, carbohydrate production, fatty acid profile, and carotenoid content
      in various species of B. braunii (LB-572, SAG 30.81, MCRC-Bb, N-836, CFTRI-Bb-1,
      and CFTRI-Bb-2) at 0.5, 1.0, and 2.0% (v/v) levels using a two-tier flask. CO2 at
      2.0% (v/v) level enhanced growth of the organism, and a two-fold increase in
      biomass and carotenoid contents was observed in all the B. braunii strains
      studied compared with control culture (without CO2 supplementation). At 1% and 2%
      (v/v) CO2 concentrations, palmitic acid and oleic acid levels increased by 2.5 to
      3 folds in one of the strains of B. braunii (LB-572). Hydrocarbon content was
      found to be above 20% at 2% CO2 level in the B. braunii LB-572, CFTRI-Bb-2, CFTRI
      Bb-1, and N-836 strains, whereas it was less than 20% in the SAG 30.81 and MCRC
      Bb strains compared with control culture. This culture methodology will provide
      information on CO2 requirement for growth of algae and metabolite production. B.
      braunii spp. can be grown at the tested levels of CO2 concentration without much
      influence on culture pH.

PMID- 18050945
TI  - Temperature effects on Korean entomopathogenic nematodes, Steinernema glaseri and
      S. longicaudum, and their symbiotic bacteria.
AB  - We investigated the temperature effects on the virulence, development,
      reproduction, and motility of two Korean isolates of entomopathogenic nematodes,
      Steinernema glaseri Dongrae strain and S. longicaudum Nonsan strain. In addition,
      we studied the growth and virulence of their respective symbiotic bacterium,
      Xenorhabdus poinarii for S. glaseri and Xenorhabdus sp. for S. longicaudum, in an
      insect host at different temperatures. Insects infected with the nematode
      bacterium complex or the symbiotic bacterium was placed at 13 degrees C, 18
      degrees C, 24 degrees C, 30 degrees C, or 35 degrees C in the dark and the
      various parameters were monitored. Both nematode species caused mortality at all
      temperatures tested, with higher mortalities occurring at temperatures between 24
      degrees C and 30 degrees C. However, S. longicaudum was better adapted to cold
      temperatures and caused higher mortality at 18 degrees C than S. glaseri. Both
      nematode species developed to adult at all temperatures, but no progeny
      production occurred at 13 degrees C or 35 degrees C. For S. glaseri, nematode
      progeny production was best at inocula levels above 20 infective juveniles/host
      at 24 degrees C and 30 degrees C, but for S. longicaudum, progeny production was
      generally better at 24 degrees C. Steinernema glaseri showed the greatest
      motility at 30 degrees C, whereas S. longicaudum showed good motility at 24
      degrees C and 30 degrees C. Both bacterial species grew at all tested
      temperatures, but Xenorhabdus sp. was more virulent at low temperatures (13
      degrees C and 18 degrees C) than X poinarii.

PMID- 18050946
TI  - Humic substances act as electron acceptor and redox mediator for microbial
      dissimilatory azoreduction by Shewanella decolorationis S12.
AB  - The potential for humic substances to serve as terminal electron acceptors in
      microbial respiration and the effects of humic substances on microbial
      azoreduction were investigated. The dissimilatory azoreducing microorganism
      Shewanella decolorationis S12 was able to conserve energy to support growth from
      electron transport to humics coupled to the oxidation of various organic
      substances or H2. Batch experiments suggested that when the concentration of
      anthraquinone-2-sulfonate (AQS), a humics analog, was lower than 3 mmol/l,
      azoreduction of strain S12 was accelerated under anaerobic condition. However,
      there was obvious inhibition to azoreduction when the concentration of the AQS
      was higher than 5 mmol/l. Another humics analog, anthraquinone-2-sulfonate
      (AQDS), could still prominently accelerate azoreduction, even when the
      concentration was up to 12 mmol/l, but the rate of acceleration gradually
      decreased with the increasing concentration of the AQDS. Toxic experiments
      revealed that AQS can inhibit growth of strain S12 if the concentration past a
      critical one, but AQDS had no effect on the metabolism and growth of strain S12
      although the concentration was up to 20 mmol/l. These results demonstrated that a
      low concentration of humic substances not only could serve as the terminal
      electron acceptors for conserving energy for growth, but also act as redox
      mediator shuttling electrons for the anaerobic azoreduction by S. decolorationis
      S12. However, a high concentration of humic substances could inhibit the
      bacterial azoreduction, resulting on the one hand from the toxic effect on cell
      metabolism and growth, and on the other hand from competion with azo dyes for
      electrons as electron acceptor.

PMID- 18050947
TI  - Biological control of strawberry gray mold caused by Botrytis cinerea using
      Bacillus licheniformis N1 formulation.
AB  - Bacillus licheniformis N1 is a biological control agent to control gray mold
      diseases caused by Botrytis cinerea. Various formulations of B. licheniformis N1
      were generated and evaluated for the activity to control strawberry gray mold.
      The wettable powder type formulation N1E was selected in pot experiments with
      remarkable disease control activity on both strawberry leaves and flowers. The
      N1E formulation contained 400 g of corn starch, 50 ml of olive oil, and 50 g of
      sucrose per a liter of bacterial fermentation culture. Optimum dilution of N1E to
      appropriately control the strawberry gray mold appeared to be 100-fold dilution
      in plastic house artificial infection experiments. The significant reduction of
      symptom development in the senescent leaves was apparent by the treatment of N1E
      at 100-fold dilution when N1E was applied before Bo. cinerea inoculation, but not
      after the inoculation. Both artificial infection experiments in a plastic house
      and natural infection experiments in the farm plastic house under production
      conditions revealed that the disease severity of gray mold on strawberry leaves
      and flowers was significantly reduced by N1E treatment. The disease control value
      of N1E on strawberry leaves was 81% under production conditions, as compared with
      the 61.5% conferred by a chemical fungicide, iprodione. This study suggests that
      our previously generated formulation of B. licheniformis N1 will be effective to
      control strawberry gray mold by its preventive activity.

PMID- 18050948
TI  - Effect of electrochemical redox reaction on growth and metabolism of
      Saccharomyces cerevisiae as an environmental factor.
AB  - The effect of an electrochemically generated oxidation-reduction potential and
      electric pulse on ethanol production and growth of Saccharomyces cerevisiae ATCC
      26603 was experimented and compared with effects of electron mediators (neutral
      red, benzyl viologen, and thionine), chemical oxidants (hydrogen peroxide and
      hypochlorite), chemical reductants (sulfite and nitrite), oxygen, and hydrogen.
      The oxidation (anodic) and reduction (cathodic) potential and electric pulse
      activated ethanol production and growth, and changed the total soluble protein
      pattern of the test strain. Neutral red electrochemically reduced activated
      ethanol production and growth of the test strain, but benzyl viologen and
      thionine did not. Nitrite inhibited ethanol production but did not influence
      growth of the test strain. Hydrogen peroxide, hypochlorite, and sulfite did not
      influence ethanol production and growth of the test strain. Hydrogen and oxygen
      also did not influence the growth and ethanol production. It shows that the test
      strain may perceive electrochemically generated oxidation-reduction potential and
      electric pulse as an environmental factor.

PMID- 18050949
TI  - Enzymatic characterization and substrate specificity of thermostable beta
      glycosidase from hyperthermophilic archaea, Sulfolobus shibatae, expressed in E.
      coli.
AB  - Enzymatic properties and substrate specificity of recombinant beta-glycosidases
      from a hyperthermophilic archaeon, Sulfolobus shibatae (rSSG), were analyzed.
      rSSG showed its optimum temperature and pH at 95 degrees C and pH 5.0,
      respectively. Thermal inactivation of rSSG showed that its half-life of enzymatic
      activity at 75 degrees C was 15 h whereas it drastically decreased to 3.9 min at
      95 degrees C. The addition of 10 mM of MnCl2 enhanced the hydrolysis activity of
      rSSG up to 23% whereas most metal ions did not show any considerable effect.
      Dithiothreitol (DTT) and 2-mercaptoethanol exhibited significant influence on the
      increase of the hydrolysis activity of rSSG. rSSG apparently preferred
      laminaribiose (beta1-->3Glc), followed by sophorose (beta1-->2Glc), gentiobiose
      (beta1-->6Glc), and cellobiose (beta1--4Glc). Various intermolecular transfer
      products were formed by rSSG in the lactose reaction, indicating that rSSG
      prefers lactose as a good acceptor as well as a donor. The strong intermolecular
      transglycosylation activity of rSSG can be applied in making functional
      oligosaccharides.

PMID- 18050951
TI  - Accurate delimitation of Phanerochaete chrysosporium and Phanerochaete sordida by
      specific PCR primers and cultural approach.
AB  - White rot fungi, Phanerochaete chrysosporium and Phanerochaete sordida, have been
      mostly studied in a variety of industrial processes like biopulping and pulp
      bleaching as well as in bioremediation. Whereas P. sordida is widely distributed
      in the North Temperate Zone, P. chrysosporium is reported in the restricted area
      and hundreds of reports have been described from a few strains of P.
      chrysosporium, which are deposited at various fungal collections in the world.
      The isolates of two species are not easily discriminated because of their
      morphological and molecular similarity. Through the ITS sequence analyses, a
      region containing substantial genetic variation between the two species was
      identified. PCR amplification using two specific primers was successfully used to
      differentiate P. chrysosporium from P. sordida. These results were supported by
      cultural studies. The growth rates at 37 degrees C on PDA, MEA, and Cza and the
      microscopic features of conidia on PDA and YMA were also very useful to
      differentiate those two species.

PMID- 18050950
TI  - Expression of enterotoxin genes in Staphylococcus aureus isolates based on mRNA
      analysis.
AB  - Staphylococcus aureus strains are important foodborne pathogens that produce
      various toxins. To evaluate the risk of the enterotoxins, four S. aureus strains
      from kinbap and two clinical samples were isolated and identified, and their
      expression of the enterotoxin genes were analyzed using a reverse transcription
      real-time PCR. Various enterotoxin genes were detected, including sea, seg, seh,
      sei, sen, seo, and sem, where each isolate contained one or two. When the mRNA
      detection of the enterotoxin genes was analyzed using a reverse transcriptase
      PCR, various levels of expression were found depending on the species and
      enterotoxin gene. Therefore, it is reasonable to suggest that the poisoning risk
      of S. aureus can be effectively evaluated based on the gene expression at the
      mRNA level.

PMID- 18050952
TI  - Escherichia coli can produce recombinant chitinase in the soil to control the
      pathogenesis by Fusarium oxysporum without colonization.
AB  - Fusarium wilt of cucumbers was effectively controlled by Escherichia coli
      expressing an endochitinase gene (chiA), and the rate was as effective (60.0%) as
      the wildtype strain S. proteamaculans 3095 (55.0%) where the gene was cloned.
      However, live cells of soil inoculated E. coli host harboring the chiA gene did
      not proliferate but declined 100-fold from 108 CFU during the first week and
      showed less than 10 cells after day 14, suggesting that E. coli was able to
      express and produce the chitinase enzyme to the soil even as the population was
      gradually decreasing. Because the majority of the strains was alive for only a
      short period of time and the Fusarium-affected seedlings showed symptoms of
      wilting within 7-10 days, it seems that the pathogen control was decided early
      after the introduction of the biocontrol agent, eliminating the survival of the
      antagonist. These results indicated that soil inoculated E. coli could
      sufficiently express and produce the recombinant protein to control the pathogen,
      and root or soil colonization of the antagonist might not be a significant factor
      in determining the efficacy of biological control.

PMID- 18050953
TI  - Rapid detection and isolation of known and putative alpha-L-arabinofuranosidase
      genes using degenerate PCR primers.
AB  - alpha-L-Arabinofuranosidases (AFases; EC 3.2.1.55) are exo-type enzymes, which
      hydrolyze terminal nonreducing arabinose residues from various polysaccharides
      such as arabinan and arabinoxylan. Genome-wide BLAST search showed that various
      bacterial strains possess the putative AFase genes with well-conserved motif
      sequences at the nucleotide and amino acid sequence levels. In this study, two
      sets of degenerate PCR primers were designed and tested to detect putative AFase
      genes, based on their three highly conserved amino acid blocks (PGGNFV, GNEMDG,
      and DEWNVW). Among 20 Bacillus-associated species, 13 species were revealed to
      have putative AFase genes in their genome and they share over 67% of amino acid
      identities with each other. Based on the partial sequence obtained from an
      isolate, an AFase from Geobacillus sp. was cloned and expressed in E. coli.
      Enzymatic characterization has verified that the resulting enzyme corresponds to
      a typical AFase. Accordingly, degenerate PCR primers developed in this work can
      be used for fast, easy, and specific detection and isolation of putative AFase
      genes from bacterial cells.

PMID- 18050954
TI  - Rapid identification of Lactobacillus and Bifidobacterium in probiotic products
      using multiplex PCR.
AB  - Lactic acid bacteria (LAB) are beneficial for the gastrointestinal tract and
      reinforce immunity in human health. Recently, many functional products using the
      lactic acid bacteria have been developed. Among these LAB, Lactobacillus
      acidophilus, Lactobacillus rhamnosus, Bifidobacterium longum, and Bifidobacterium
      bifidum are frequently used for probiotic products. In order to monitor these LAB
      in commercial probiotic products, a multiplex PCR method was developed. We
      designed four species-specific primer pairs for multiplex PCR from the 16S rRNA,
      16S-23S rRNA intergenic spacer region, and 23S rRNA genes in Lactobacillus
      acidophilus, Lactobacillus rhamnosus, Bifidobacterium longum, and Bifidobacterium
      bifidum. Using these primer pairs, 4 different LAB were detected with high
      specificity in functional foods. We suggest that the multiplex PCR method
      developed in this study would be an efficient tool for simple, rapid, and
      reliable identification of LAB used as probiotic strains.

PMID- 18050955
TI  - A discrete mathematical model applied to genetic regulation and metabolic
      networks.
AB  - This paper describes the use of a discrete mathematical model to represent the
      basic mechanisms of regulation of the bacteria E. coli in batch fermentation. The
      specific phenomena studied were the changes in metabolism and genetic regulation
      when the bacteria use three different carbon substrates (glucose, glycerol, and
      acetate). The model correctly predicts the behavior of E. coli vis-a-vis
      substrate mixtures. In a mixture of glucose, glycerol, and acetate, it prefers
      glucose, then glycerol, and finally acetate. The model included 67 nodes; 28 were
      genes, 20 enzymes, and 19 regulators/biochemical compounds. The model represents
      both the genetic regulation and metabolic networks in an inrtegrated form, which
      is how they function biologically. This is one of the first attempts to include
      both of these networks in one model. Previously, discrete mathematical models
      were used only to describe genetic regulation networks. The study of the network
      dynamics generated 8 (2(3)) fixed points, one for each nutrient configuration
      (substrate mixture) in the medium. The fixed points of the discrete model reflect
      the phenotypes described. Gene expression and the patterns of the metabolic
      fluxes generated are described accurately. The activation of the gene regulation
      network depends basically on the presence of glucose and glycerol. The model
      predicts the behavior when mixed carbon sources are utilized as well as when
      there is no carbon source present. Fictitious jokers (Joker1, Joker2, and
      Repressor SdhC) had to be created to control 12 genes whose regulation mechanism
      is unknown, since glycerol and glucose do not act directly on the genes. The
      approach presented in this paper is particularly useful to investigate potential
      unknown gene regulation mechanisms; such a novel approach can also be used to
      describe other gene regulation situations such as the comparison between non
      recombinant and recombinant yeast strain, producing recombinant proteins,
      presently under investigation in our group.

PMID- 18050956
TI  - Increasing production in Korean shrimp farms with white-spot syndrome virus PCR
      negative brood stock.
AB  - White-spot syndrome virus (WSSV) is a devastating, infectious virus affecting
      shrimp. Although sensitive techniques involving PCR have been developed to assist
      farmers in screening shrimp (brood stock) for WSSV prior to stocking ponds, such
      practices have not yet been applied in Korea. Despite the rationality of
      implementing screening, there has been some doubt as to whether the stocking of
      WSSV-PCR-negative fry epidemiologically decreases white-spot disease outbreaks.
      Here, we report a retrospective analysis of data from shrimp farms in the western
      coast of Korea where WSSV-PCR-negative brood stocks were used to stock rearing
      ponds. A total of 366 shrimp from Heuksan Island were sampled for WSSV with PCR.
      Of the tested shrimp, 7.2% (28 brood stocks) were identified as WSSV positive;
      only WSSV-PCR-negative shrimp were used for brood stocks. Total unit production
      (final shrimp production/ the area of the ponds) was higher, at 1.96, in ponds
      where WSSV-PCR-negative shrimp were used, as compared with 1.02 in other ponds in
      Korea in 2004. This retrospective analysis of WSSV in Korea may be useful to the
      shrimp aquaculture industry, suggesting a testable hypothesis that may contribute
      to the eventual control of WSSV outbreaks.

PMID- 18050957
TI  - Rapid detection of Enterobacter sakazakii using TaqMan real-time PCR assay.
AB  - Enterobacter sakazakii is an emerging food pathogen, which induces severe
      meningitis and sepsis in neonates and infants, with a high fatality rate. The
      disease is generally associated with the ingestion of contaminated infant
      formula. In this study, we describe the development of a real-time PCR protocol
      to identify E. sakazakii using a TaqMan probe, predicated on the nucleotide
      sequence data of the 16S rRNA gene obtained from a variety of pathogens. To
      detect E. sakazakii, four primer sets and one probe were designed. Five strains
      of E. sakazakii and 28 non-E. sakazakii bacterial strains were used in order to
      ensure the accuracy of detection. The PCR protocol successfully identified all of
      the E. sakazakii strains, whereas the 28 non-E. sakazakii strains were not
      detected by this method. The detection limits of this method for E. sakazakii
      cells and purified genomic DNA were 2.3 CFU/assay and 100 fg/assay, respectively.
      These findings suggest that our newly developed TaqMan real-time PCR method
      should prove to be a rapid, sensitive, and quantitative method for the detection
      of E. sakazakii.

PMID- 18050958
TI  - Physical properties of nisin-incorporated gelatin and corn zein films and
      antimicrobial activity against Listeria monocytogenes.
AB  - Edible films of gelatin and corn zein were prepared by incorporating nisin to the
      film-forming solutions. Corn zein film with nisin of 12,000 IU/ml had an increase
      of 11.6 MPa in tensile strength compared with the control, whereas gelatin film
      had a slight increase with the increase of nisin concentration added. Water vapor
      permeability for both corn zein and gelatin films decreased with the increase of
      nisin concentration, thus providing a better barrier against water. Antimicrobial
      activity against Listeria monocytogenes increased with the increase of nisin
      concentration, resulting in 1.4 log cycle reduction for corn zein film and 0.6
      log cycle reduction for gelatin film at 12,000 IU/ml. These results suggest that
      incorporation of nisin into corn zein and gelatin films improve the physical
      properties of the films as well as antimicrobial activity against pathogenic
      bacteria during storage, resulting in extension of the shelf life of food
      products by providing with antimicrobial edible packaging films.

PMID- 18050959
TI  - Physiological responses of Bacillus amyloliquefaciens spores to high pressure.
AB  - Pressure inactivation behavior of Bacillus amyloliquefaciens spores was
      investigated in deionized water. The spores of B. amyloliquefaciens were
      subjected to 105 degrees C and 700 MPa. The magnitude of the decrease in
      viability after pressure treatment was similar to that after pressure treatment
      followed by heat shock. The increase of dipicolinic acid (DPA) release was
      correlated with the spore inactivation, and the hydrophobicity did not
      significantly change during the pressure-assisted thermal processing (PATP). Lag
      phase duration increased with increasing pressure process time. The mechanisms of
      spore germination and inactivation during the PATP were related to a complex
      physiological process.

PMID- 18050960
TI  - Antimicrobial effects of flavone analogues and their structure-activity
      relationships.
AB  - It has been well known that the use of Saccharomyces cerevisiae can cause
      fungemia in critically ill patients and flavone shows an antimicrobial effect on
      S. cerevisiae. Therefore, we have investigated the activities of thirteen flavone
      analogues on S. cerevisiae in our studies. Because flavonoids including flavones
      have antioxidative effects, we try to carry out the activity studies of flavone
      analogues in vitro and in vivo. In addition, the relationships between the
      structures of flavone analogues and their biological activities, such as
      antimicrobial and antioxidative effects, were elucidated using Comparative
      Molecular Field Analysis calculations. Of the flavone analogues tested here, 3,2'
      dihydroxyflavone showed both good antimicrobial and antioxidative activities.

PMID- 18050961
TI  - Comparative transcriptome analysis for avermectin overproduction via Streptomyces
      avermitilis microarray system.
AB  - Avermectin and its analogs are major commercial antiparasitic agents in the
      fields of animal health, agriculture, and human infections. To increase our
      understanding about the genetic mechanism underlying avermectin overproduction,
      comparative transcriptomes were analyzed between the low producer S. avermitilis
      ATCC31267 and the high producer S. avermitilis ATCC31780 via a S. avermitilis
      whole genome chip. The comparative transcriptome analysis revealed that fifty S.
      avermitilis genes were expressed at least two-fold higher in S. avermitilis
      ATCC31780. In particular, all the avermectin biosynthetic genes, including
      polyketide synthase (PKS) genes and an avermectin pathway-specific regulatory
      gene, were less expressed in the%low producer S. avermitilis ATCC31267. The
      present results imply that avermectin overproduction in S. avermitilis ATCC31780
      could be attributed to the previously unidentified fifty genes reported here and
      increased transcription levels of avermectin PKS genes.

PMID- 18050962
TI  - Glycosylation of flavonoids with E. coli expressing glycosyltransferase from
      Xanthomonas campestris.
AB  - Glycosyltransferase family 1 (UGT) uses small chemicals including phenolics,
      antibiotics, and alkaloids as substrates to have an influence in biological
      activities. A glycosyltransferase (XcGT-2) from Xanthomonas campestris was cloned
      and consisted of a 1,257 bp open reading frame encoding a 45.5 kDa protein. In
      order to use this for the modification of phenolic compounds, XcGT-2 was
      expressed in Escherichia coli as a glutathione S-transferase fusion protein. With
      the E. coli transformant expressing XcGT-2, biotransformation of flavonoids was
      carried out. Flavonoids having a double bond between carbons 2 and 3, and
      hydroxyl groups at both C-3' and C-4', were glycosylated and the glycosylation
      position was determined to be at the hydroxyl group of C-3', using nuclear
      magnetic resonance spectroscopy. These results showed that XcGT-2
      regiospecifically transferred a glucose molecule to the 3'-hydroxyl group of
      flavonoids containing both 3' and 4'-hydroxyl groups.

PMID- 18050964
TI  - [Who will protect physicians?].

PMID- 18050963
TI  - Synthesis and biological activity of fungal metabolite, 4-hydroxy-3-(3'-methyl-2'
      butenyl)-benzoic acid.
AB  - 4-Hydroxy-3-(3'-methyl-2'-butenyl)-benzoic acid (HMBA) was previously isolated
      from Curvularia sp. KF119 as a cell-cycle inhibitor. However, the present study
      used a novel and practical synthetic method to prepare a large quantity of HMBA.
      The synthetic HMBA was found to inhibit the cell-cycle progression of HeLa cells
      with a comparable potency to the natural fungal metabolite. The inhibition of the
      cell-cycle progression by the synthetic HMBA involved both the activation of
      p21(WAFI) and the inhibition of cyclin Dl expression in the cells. Consequently,
      this new synthetic procedure provides an easy and convenient way to produce or
      manipulate the original fungal metabolite.

PMID- 18050965
TI  - [Role and significance of poison control centers].

PMID- 18050966
TI  - [Influence of mental disorders on working ability assessment].
AB  - BACKGROUND/AIM: There is an increasing need for evaluation of working ability due
      to lower level of social protection of workers and growing number of patients
      with mental diseases in Bosnia and Herzegovina (B&H). The aim of this study was
      to establish the influence of mental diseases on the occurrence of disability of
      I and III categories in B&H during the period from January 1st 2005 to December
      31st 2006. METHODS: This study involved 1792 examinees with the complete loss of
      working ability (I disability category) (n = 921). Disability category III
      consisted of persons with limited working ability (n = 871). The instruments of
      research in this multricentric and retrospective study were the forms P-6 and D-2
      for the years of service in B&H, and the form IN for persons with years of
      service abroad and personal features questionnaire (EPQ). RESULTS: The study
      included 1494 men (78.5%) and 298 women (21.5%). Univariant analysis represented
      very high statistical significance (p = 0.001) concerning: age (X2 = 65.428),
      years of service (X2=28.438), drinking (X2 = 33.234), smoking (X2=70.880),
      father's education (X2 = 58.124), migrations (X2 = 14.874), sick leave (X2 =
      29.190), medical treatment (X2 = 95.073) and rehabilitation (X2 = 29.453).
      Multivariant analysis represented the influence on disability cate gory I by
      parameters such as: years of service, sick leave, psychoticism and depression (p
      = 0.001). Hospital treatment and fatigation had influence on disability in both
      groups. Mental diseases are the leading cause in disability category I in 14.98%
      and in disability category III in 9.3% persons. Leading diseases in both
      disability categories were depression and schizophrenia followed by alcoholism,
      anxiety, brain organ psychosyndrome (BOPS) and other diseases. CONCLUSION: The
      following parameters have highest influence on the disability category: the years
      of service, sick leave, psychoticism, depression, and long-lasting disease,
      medical treatments and fatigation on the disability category III.

PMID- 18050967
TI  - [Analytical confirmation of lethal heroin overdose by the use of liquid
      chromatography methods].
AB  - BACKGROUND/AIM: Heroin is diacetylated morphine. Its ability to induce euphoria
      has led to its frequent abuse, giving rise to psychological and physical
      dependence. It has a short half-life, of approximately 2-6 min. In the brain,
      heroin undergoes deacetylation to 6-monoacetylmorphine (6-MAM) and morphine.
      Detection of 6-acetylmorphine in the urine is indicative of heroin use. The aim
      of this study was to compare sensitivity and reliability of two analytical
      methods, a multicolumn liquid chromatography system with UV scanning detector
      (HPLC-UV) and liquid chromatography-mass spectrometry detection (LC-MS) in opiate
      determining in post mortem material. METHODS: Post mortem samples (blood, urine
      and vitreous humor) were analyzed by liquid chromatography with UV and MS
      detection. The samples were prepared by liquid-liquid extraction with mixture
      chloroform-isopropanol (9:1). Separation was performed on C8 column with mobile
      phase composed of 55% acetonitrile-glacial acetic acid (99:1) and 45% 20 mM
      ammonium acetate. RESULTS: The analysis of blood samples, urine, and eye liquid
      by the use of multicolumn HPLC-UV method confirmed the presence of morphine in
      the samples of blood and urine, codeine only in urine, and 6-MAM in the samples
      of urine and eye liquid. Using LC-MS method morphine was confirmed in all of the
      samples, while codeine was confirmed in urine and in the sample of eye liquid. In
      the samples of eye liquid and urine 6-MAM was confirmed. CONCLUSION: For
      determination of opiates in post mortem material LC-MS technique is more
      sensitive and reliable as compared to multicolumn liquid chromatography.

PMID- 18050968
TI  - [Vitamin B2 content determination in liver paste by using acid and acid-enzyme
      hydrolysis].
AB  - BACKGROUND/AIM: Vitamin B2 is available in foodstuff in the form of coenzyme and
      in free form. For its content determination a few procedures should be performed
      (deliberation from a complex, extraction of free and deliberated form) and
      detection, identification and quantification. There is a particular problem in
      determination of vitamin B2 in the meat products. For a determination of total
      vitamin B2 content in liver paste two preparation procedures are compared: acid
      and acid-enzymatic hydrolysis. The aim of this study thus, was to compare the
      effectivenes of these two different procedures for vitamin B2 content
      determination in liver paste. METHODS: High pressure liquid chromatography (HPLC)
      method with fluorescence detector, as specific and adequately sensitive for the
      foodstuff of a complex composition with a natural vitamin content, was used for
      determination of vitamin B2 in liver paste. Acid hydrolysis was performed with
      the application 0.1 M hydrochloric acid in a pressure cooker, and enzymatic
      hydrolysis was performed with the 10% takadiastase on 45 degrees C within four
      hours. Ten samples of liver paste from the supply of the Serbian Army were
      examined. Separation was performed on the analytical column Nucleosil 50-5 C18
      with mobile phase 450 ml CH3OH + 20 ml 5 mM CH3COONH4, and detection on the
      fluorescent detector with the variable wave length. Both methods were validated:
      examining a detection limit, quantification limit, specificity (because of a
      possible B2 vitamin interference with reagents), linearity of a peak area and
      standard concentration of B2 vitamin ratio in the range from 0.05 microg/ml to 2
      microg/ml, precision for the 0.05 microg/ml concentration and recovery. RESULTS:
      All the previously examined parameters validated both methods as specific,
      precise and reproductive, with a high recovery (98.5% for acid and 98.2% for acid
      enzymatic hydrolysis), as well as linearity in a range that significantly
      superseded the expected content in the samples (r = 0.9994, and r = 0.99987).
      Hydrolysis procedures make a sample suitable for vitamin B2 determination. In the
      liver paste samples a high content of vitamin B2 was determined: 0.83 mg/100 g
      after acid hydrolysis, and 0.909 mg/100 g after acid-enzyme hydrolysis. There
      were statistically significantly higher values determined after the acid-enzyme
      hydrolysis (p < 0.05). CONCLUSION: Using acid-enzyme hydrolysis and separation
      instrument technique (liquid chromatography) with a fluorescent detector as
      detection system, statistically significantly greater vitamin B2 quantities were
      determined than after using acid hydrolysis procedure. Vitamin B2 content
      determined in ten liver paste samples was high (0.881-0.936 mg/100 g) indicating
      that this meat product is a good vitamin B2 source.

PMID- 18050970
TI  - Computer-assisted quantitative analysis of Ki-67 antigen in dysplasia--associated
      lesions or masses in ulcerative colitis.
AB  - BACKGROUND/AIM: The aim of this study was to apply computer-assisted methodology
      in assessment of Ki-67 positivity in "adenoma-like" dysplasia associated lesions
      or masses (DALMs), and carcinoma in ulcerative colitis (UC), and to determine a
      new approach to grading of Ki-67 staining intensity. METHODS: Immunohistochemical
      slides were quantitatively analyzed for estimation of proportion and intensity of
      Ki-67 positive-stained cells in a total of 50 "adenoma-like" DALMs (27 with low
      grade dysplasia and 23 with high-grade dysplasia), and 17 adenocarcinomas
      associated with UC. The four grades of immunohistochemical staining intensity
      were established by an automated classification of nuclear optical densities.
      RESULTS: The Ki-67 labeling index (LI) in low-grade dysplasia was significantly
      lower than in high-grade dysplasia, and carcinoma (p < 0.001). The Ki-67 LI of
      carcinomas was not significantly different from the value obtained in high-grade
      dysplasia (p > 0.05), however having the difference in percentage values of the
      moderate stained nuclei (p < 0.05). The overall average values of chromogene
      nuclear optical density, showed statistically significant differences between
      DALMs and carcinoma (p < 0.05), although not between normal mucosa and low-grade
      dysplasia (p > 0.05). CONCLUSION: The obtained results imply, according to the
      overall percentage of labeled nuclei, that high-grade dysplasia is very close to
      carcinoma, while there is the difference in the percentage of moderately stained
      nuclei. We showed that Ki-67 positivity have a different internal distribution
      which could be useful in analysing these lesions. These findings also, indicate
      the important biological differences between low-grade dysplasia and carcinoma in
      UC, and a low proliferative potential of the former. Automated image analysis
      permits an objective [corrected] estimation of Ki-67 immunohistochemical staining
      in UC-associated dysplasia and carcinoma.

PMID- 18050969
TI  - [Cardiovascular risk factors in patients with subclinical hypothyroidism].
AB  - BACKGROUND/AIMS: Overt hypothyroidism is disease associated with accelerated
      arteriosclerosis and coronary heart disease. Whether subclinical hypothyroidism
      (SH) is associated with increased cardiovascular risk is contraversial. As SH is
      a high prevalence thyroid dysfunction, specially in older women, it is important
      to evaluate cardiovascular risk factors in these patients and that was the aim of
      this study. METHODS: We examined 30 patients with SH and 20 healthy controls.
      Subclinical hypothireoidism was defined as an elevated thyrotropin (TSH) (> 4.5
      mU/L) and normal free thyroxine (FT4) level. In all the participants we
      determined body mass index (BMI), blood pressure, TSH, FT4, antibodies to thyroid
      peroxidase, antibodies to thyroglobulin, total cholesterol, high density
      lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol,
      triglicerides, total cholesterol/HDL cholesterol ratio and LDL/HDL cholesterol
      ratio. RESULTS: Mean BMI in patients with SH was significantly higher (p < 0.05),
      as well as diastolic blood pressure (p < 0.01) compared with the controls.
      Average levels of total cholesterol (5.40 +/- 0.62 vs 5.06 +/- 0.19 mmol/l, p <
      0.01) and triglycerides (2.16 +/- 0.56 vs 1.89 +/- 0.24 mmol/l, p < 0.05) were
      also significantly higher in the group with SH. Individual analysis revealed that
      the percentage of patients with SH having borderline elevated total cholesterol
      (63.33%), hypertrigliceridemia (43.33%) and elevated total cholesterol/HDL
      cholesterol ratio (26.67%) were significantly higher than the percentage in the
      controls. No significant correlation between TSH and lipid parameters was
      detected. CONCLUSION: Subclinical hypothyroidism was associated with higher BMI,
      diastolic hypertension, higher total cholesterol and triglicerides levels and
      higher total cholesterol/HDL cholesterols ratio. This might increase the risk of
      accelerated arteriosclerosis in patients with SH.

PMID- 18050971
TI  - [Risk factors for the appearance of central venous catheters colonisation].
AB  - INTRODUCTION/AIM: Intravascular device placement (IVD) is a part of everyday
      medical practice, however, its application is associated with a high risk of
      onset of nosocomial infections (NI) and increased mortality and morbidity.
      Nosocomial blood infections (NBIs) account for 10% of all the registered NI. NBIs
      are more frequent in patients with a placed IVD and it present an important risk
      factor for the onset of NBI, i.e. catheter-associated NBIs (CANBIs). Pathogenesis
      of CANBIs is complex and conditioned by the presence of different characteristics
      related to a catheter, patient and a specific causative organism. The most common
      CRBSI causes include coagulase-negative staphylococcus, S. aureus, Enterobacter
      spp, Candida spp, Klebsiella spp, Pseudomonas spp. and Enterococcus spp. METHODS:
      All the patients hospitalized at the Intensive Care Department of the Clinic of
      Digestive Diseases over the period January 1, 2004-September 1, 2004 were
      retrospectively analyzed. The study included 107 patients in whom central venous
      catheter (CVC) was placed for more than 48 h. All the causes isolated from a CVC
      segment were recorded. Culture, isolation and identification of the causative
      organisms were performed using standard microbiological methods in the
      Bacteriological Laboratory within the Emergency Center, Clinical Center of
      Serbia. Catheter segment samples (tip of the CVC 3-5 cm long) were analyzed.
      Based on the insight into medical documentation, patients' examination and
      medical staff interview, catheter and patient-related characteristics were
      recorded. RESULTS: A total of 107 CVCs were analyzed, out of which 56 (52%) were
      sterile while 51 (48%) were colonized. The results of our study evidenced that
      total parenteral nutrition (TPN) (p < 0.05), number of catheterization days (p <
      0.05), and central venous pressure measurement (p < 0.05) were significantly
      associated with CVC colonization. In this study, no statistically significant
      difference in catheter colonization was found with respect to sex, age,
      anatomical insertion site and CVC placement site. CONCLUSION: According to the
      results of our study, TPN, the number of catheterization days and measurement of
      central venous pressure play major roles in colonization of CVC. Understanding
      risk factors associated with CVC colonization and onset of CANBIs is a
      prerequisite for quality preventive work of health professionals.

PMID- 18050972
TI  - [Pathogenesis of Alzheimer disease].

PMID- 18050973
TI  - [Treatment of hepatorenal syndrome].

PMID- 18050974
TI  - [Class II malocclusion therapy using fixed orthodontic appliance].
AB  - BACKGROUND: Depending on the indication, and the age of a patient, class II
      division I malocclusion can be treated by a fixed or mobile orthodontic
      appliance, with or without teeth extraction. CASE REPORT: A treatment of a male
      patient, 15 years old, with dentoalveolar class II division I was described. On
      the base of clinical findings, study case analysis, analysis of orthopan and
      profile cephalogram, there were class II division I with protrusion of frontal
      teeth and mild crowding in lower jaw assesed. The patient was treated by fixed
      orthodontics appliances (SWA Roth .022") in both jaws for 18 months, with the
      retention period of the same length. CONCLUSION: Fixed ortodontic appliances are
      necessary when bodily movement of the teeth is indicated--in this case for
      cuspids distalization and retraction of incisors.

PMID- 18050975
TI  - [Identification of residual ischemia in the occluded coronary artery irrigation
      area using myocardial perfusion scintigraphy].
AB  - BACKGROUND: Inspite the indisputable significance of coronarography, the
      implications of a revealed stenosis--and how close it is to occlusion could vary
      in regard to its physiological importance. Myocardial perfusion scintigraphy
      (MPS) possiblity to prove and objectivise the presence of ischemia and myocardial
      viability within an occlusion found coronarographically is especially significant
      since it makes possible to the clinitian to choose an adequate therapy. CASE
      REPORT: We reported a 43-year-old male patient who had been hospitalized to
      another institution due to acute myocardial infarction (AMI) of posterolateral
      localisation. Following the acute AMI stage the ergometric test per Bruce
      protocole was performed, negative to ischemic heart disease, while multislice
      computed tomography showed no significant changes on the coronary arteries. The
      performed one-day-protocole MPS showed a massive area of residual ischemia within
      myocardial infarction (MI) type culprit lesion of the posterolateral zone
      starting from the subapical level to the basal cross-section. According to the
      MPS findings coronarography was indicated due to a revascularisation assessment.
      The performed coronarography revealed an occlusion of the circumflex coronary
      artery (CCA) right after the division of obtuse branch (OB) that presented
      discretely in the distal parts from the homo- and heterocolaterals. The distal
      portion of CCA presented discretely out off the right coronary artery (RCA).
      Echocardiography confirmed an ejection fraction of 50% with hypokinesia of
      inferior and posterior walls, as well as the septum, showing a mild reduction of
      the general contractility. Flows through confluences were well. A month after MI
      a percutane coronary intervention (PCI) was performed with the implantation of a
      drug-releasing stent (Taxus). Early after PCI (within two weeks) a control MPS
      was done to evaluate the effects of the therapy giving the normal findings of
      myocardial perfusion. CONCLUSION: Determination and identificantion of vivid but
      ischemic myocard of culprit lesion type in the occluded artery irrigation zone
      enable making choice of the best therapy for a patient.

PMID- 18050976
TI  - Atypical pyoderma gangrenosum in a patient with osteomyelofibrosis.
AB  - BACKGROUND: Atypical forms of pyoderma gangrenosum generally appear on the upper
      extremities; most frequently they are associated with myeloproliferative
      disorders, including osteomyelofibrosis. A response to systemic steroids is more
      pronounced than in classical form. Sometimes it may be the first sign of an
      underlying malignancy. CASE REPORT: We reported a patient with atypical pyoderma
      gangrenosum developed during the course of a myeloid malignancy-
      osteomyelofibrosis. The lesions occurred after a minor trauma. Painful blistering
      plaques, with an elevated, bluish-gray border were located on the dorsal aspect
      of hands. No skin malignancy was found. The lesions resolved rapidly to systemic
      steroids. CONCLUSION: Considering the unusual clinical presentation which makes
      the diagnosis difficult, as well as the fact that atypical forms of pyoderma
      gangrenosum can be the first sign of malignancies, especially myeloproliferative
      ones, recognizing this entity enables timely guiding future investigations toward
      their prompt detection.

PMID- 18050977
TI  - [The Poison Control Centre in the Military Medical Academy--organization and
      activities in a ten-year period].

PMID- 18050978
TI  - Orientation to a provider unit.
AB  - This column reviews the process of orienting a program coordinator into a newly
      created position of nurse planner for an American Nurses Credentialing Center
      accredited provider unit. Examples of the orientation plan and components of the
      process are addressed.

PMID- 18050979
TI  - Assessing the bleeding patient: factors affecting hemostasis and common
      coagulation studies.
AB  - This column discusses the factors affecting hemostasis and the common coagulation
      studies used to assess patients with bleeding disorders.

PMID- 18050980
TI  - Guidelines for asking questions.
AB  - This column discusses guidelines for asking questions to improve communication in
      clinical, academic, and other settings.

PMID- 18050981
TI  - Approaches to gathering evidence for educational practices in nursing.
AB  - There are many initiatives under way to teach nursing staff about evidence-based
      practice, but how many educators seek evidence as a basis for their teaching?
      Nursing education needs more higher quality research, teachers willing to
      question their current practices, and nurse educators who ask whether there is a
      better way of promoting learning and performance. This article provides a
      perspective of how nurse educators can develop an evidence-based approach to
      their teaching using the research that is available in nursing education.

PMID- 18050982
TI  - Development of a postbasic critical care program for registered nurses: a
      collaborative venture between education and practice.
AB  - This article describes a collaborative venture between nursing education and
      nursing practice focused on continuing education. A province-wide assessment of
      the educational needs of registered nurses identified the need to create a
      critical care education program. A critical care project team was established to
      develop a Postbasic Critical Care Program for registered nurses. The development
      of the project team, initiation of the program, and the mutual benefits and
      challenges posed by this collaborative venture are presented.

PMID- 18050983
TI  - The role of the clinical nurse specialist in promoting evidence-based practice
      and effecting positive patient outcomes.
AB  - Clinical nurse specialists (CNSs) are vital members of the healthcare delivery
      leadership team. The knowledge and expertise of the CNS is germane to the quality
      of care a patient receives. More than 50 CNSs practice at Massachusetts General
      Hospital (the state's first Magnet hospital), where they share their clinical
      skills, mentor staff through difficult situations, identify learning needs, and
      implement innovative approaches to patient care. This article presents a brief
      history of the CNS role and describes how the CNS role is operationalized at
      Massachusetts General Hospital and its impact on unit-based and organizational
      outcomes. In addition, several programs and interventions identified by the CNSs
      in response to results of the Staff Perception of the Professional Practice
      Environment Survey are discussed. How the CNS influences the professional
      development of staff and potential implications for the future role of the CNS
      are described. An exemplar is included depicting a typical work day of a CNS on
      an acute adult medical unit.

PMID- 18050984
TI  - Improving program documentation quality through the application of continuous
      improvement processes.
AB  - Maintaining the integrity of record keeping and retrievable information related
      to the provision of continuing education credit creates challenges for a large
      organization. Accurate educational program documentation is vital to support the
      knowledge and professional development of nursing staff. Quality review and
      accurate documentation of programs for nursing staff development occurred at one
      institution through the use of continuous improvement principles. Integration of
      the new process into the current system maintains the process of providing
      quality record keeping.

PMID- 18050985
TI  - The Human Capital Competencies Inventory for developing nurse managers.
AB  - BACKGROUND: Nurse managers play a vital role in healthcare delivery systems.
      Psychometrically sound measures of management practices grounded in empirical
      practice data are needed. METHOD: An integrative review provided content domain
      for the Human Capital Competencies Inventory (HCCI). Analyses from nurse managers
      in one northeastern state revealed considerable consistency in performance of
      activities. RESULTS: There is validity and reliability for the HCCI with the
      sample used. CONCLUSIONS: There is early support for the Mastery Path as a
      competency-based model for developing nurses for management in healthcare
      organizations. Development and testing of four other management practices in the
      Mastery Path is ongoing.

PMID- 18050986
TI  - [IT solutions on their way].

PMID- 18050987
TI  - [After the Chernobyl accident: no basis for increased cancer risk in Sweden].

PMID- 18050988
TI  - [Researching physicians soon "endangered" species?].

PMID- 18050989
TI  - [Omega-3-fatty acids protect against dementia. Also early symptoms of mild
      Alzheimer disease seem to be inhibited].

PMID- 18050990
TI  - [Research support more often granted to male than female researchers. The
      distribution is mostly explained by formal competence differences].

PMID- 18050991
TI  - ["Broken heart" or Takotsubo cardiomyopathy mostly in postmenopausal women.
      Stress-induced condition resembling acute myocardial infarction].

PMID- 18050992
TI  - [Results following implementation of PCI in Varmland. 30-day mortality after
      myocardial infarction halved].

PMID- 18050993
TI  - [Fraud reporting as "punishment"].

PMID- 18050994
TI  - [(Where is) the crisis of psychiatry?].

PMID- 18050995
TI  - [Costa's world and mine].

PMID- 18050996
TI  - [Clinical nutrition--big tasks demand mustering of strength].

PMID- 18050997
TI  - [House calls wanted].

PMID- 18050998
TI  - [Low dosage CT is insignificant as regular radiography in the diagnosis of
      rhinosinusitis].

PMID- 18050999
TI  - [A pupil of Florence Nightingale became a pioneer in Sweden].

PMID- 18051000
TI  - A new age of professional responsibility.

PMID- 18051001
TI  - Clinical effectiveness of two microabrasion materials for the removal of enamel
      fluorosis stains.
AB  - This study evaluated the effectiveness of two microabrasion products for the
      removal of enamel fluorosis stains. Using a split-mouth study design, two
      operators used PREMA (PM) and Opalustre (OP) to remove fluorosis-like stains from
      36 subjects (10-12 years old). Both products were rubbed onto the surface of the
      affected teeth for 30 seconds. This procedure was repeated five times during each
      clinical appointment. A maximum of three clinical appointments were scheduled.
      The subjects and/or their parents were questioned about their satisfaction with
      the treatment. Two blinded evaluators appraised both sides of the mouth using a
      visual scale system. The data were analyzed by Friedman repeated measures ANOVA
      and Wilcoxon test. The majority of the subjects (approximately 97%) reported
      satisfaction at the end of the treatment (p = 0.0001). A significant improvement
      in appearance was detected after the second clinical appointment when using PREMA
      and Opalustre (p < 0.002). After the first clinical appointment, OP showed a
      statistically higher mean rating for improvement in appearance (3.4 +/- 0.7) than
      PM (2.4 +/- 0.5) (p = 0.002).

PMID- 18051002
TI  - Clinical measurement of palatal tooth wear following coating by a resin sealing
      system.
AB  - This study investigated the hypothesis that coating eroded teeth with a resin
      based dentin bonding agent gave protection from tooth wear. Nineteen adults with
      palatal tooth wear exposing dentin were recruited, following referral by their
      general dental practitioner. Alternate teeth were coated with the resin adhesive,
      while the uncoated teeth acted as controls. Accurate impressions of the eroded
      teeth, onto which were cemented machined stainless steel discs to act as
      reference areas, were scanned with a non-contacting laser profilometer at 3, 6,
      12 and 24 months. The mean thickness of resin at baseline application was 0.15 mm
      and, from 0 to 6 months, the rate of wear of the control teeth was higher than
      those covered with Seal & Protect. There was a statistically significant
      difference in "wear" measured between resin covered and control teeth at three
      months. The Inter Class Correlations (repeated measurements) for the step heights
      obtained for the original and repeat impressions was excellent at 0.99. This
      study shows that coating eroded teeth with a resin-based adhesive has the
      potential to prevent further tooth wear.

PMID- 18051003
TI  - Clinical evaluation of three desensitizing agents in relieving dentin
      hypersensitivity.
AB  - OBJECTIVES: This in vivo study determined whether the application of three
      different desensitizing agents on exposed dentin surfaces was effective in
      reducing dentin hypersensitivity in subjects with slight-to-moderate sensitivity.
      METHODS: Sixty patients with a history of sensitivity were included in this
      study. At baseline visit, the initial sensitivity levels were recorded using a
      visual analog scale (VAS). In order to activate the sensitivity, evaporative (air
      blast) and thermal (chloraethyl) stimuli were applied to each subject. The
      subjects' responses to the stimuli were marked on the VAS. Then, the subjects
      were assigned to one of the treatment groups or to a placebo. The agents used
      were Seal&Protect (Dentsply DeTrey GmbH, Konstanz, Germany), Vivasens (Ivoclar
      Vivadent AG, Schaan, Liechtenstein) and BisBlock (BISCO, Schaumburg, IL, USA);
      whereas, distilled water was used as the placebo. The subjects were recalled
      after four weeks, and their responses were again recorded. RESULTS: The VAS
      scores of the treatment and placebo groups were not different from each other at
      baseline (p > 0.05), and thermal stimuli caused higher patient discomfort than
      evaporative stimuli (p < 0.05). Alleviation effects of the desensitizing agents
      were not significantly different from each other; however, the placebo was an
      exception (p < 0.05). The differences between the VAS scores at baseline and
      after four weeks were significant for all three desensitizing agents (p < 0.05).
      However, in the placebo group, the evaporative stimuli led to insignificant pain
      variations (p > 0.05). CONCLUSION: It was concluded that the desensitizing agents
      used in this clinical study were effective in alleviating dentin
      hypersensitivity. Meanwhile, the placebo response was shown to play a significant
      role.

PMID- 18051004
TI  - In vivo study of two carbamide peroxide gels with different desensitizing agents.
AB  - This study evaluated tooth whitening and sensitivity that occurred during and
      after 14 days of overnight bleaching with 15% carbamide peroxide gel with
      potassium nitrate and fluoride (Opalescence 15% PF, OP) and 16% carbamide
      peroxide with amorphous calcium phosphate (Nite White 16%, NW). Thirty-two
      subjects bleached their teeth using custom trays. The subjects had a baseline
      evaluation and returned after 7, 14, 21, 35 and 90 days for subjective and
      objective color evaluations. The subjects also recorded daily tooth and gingival
      sensitivity. The treatments were compared for differences in mean L*, a*, b* and
      shade guide rank order at baseline and each appointment thereafter, using
      repeated measures analysis of variance (ANOVA). OP and NW showed significant
      tooth whitening. Subjects using OP were significantly lighter in b* and E* than
      those using NW, while exhibiting no difference in tooth or gingival sensitivity
      overall or during any evaluation.

PMID- 18051005
TI  - Survival of inlays and partial crowns made of IPS empress after a 10-year
      observation period and in relation to various treatment parameters.
AB  - This study evaluated the long-term survival of inlays and partial crowns made of
      IPS Empress. For this purpose, the patient data of a prospective study were
      examined in retrospect and statistically evaluated. MATERIALS AND METHODS: All of
      the inlays and partial crowns fabricated of IPS-Empress within the Department of
      Operative Dentistry at the School of Dental Medicine of Philipps University,
      Marburg, Germany were systematically recorded in a database between 1991 and
      2001. The corresponding patient files were revised at the end of 2001. The
      information gathered in this way was used to evaluate the survival of the
      restorations using the method described by Kaplan and Meyer. RESULTS: A total of
      n = 1624 restorations were fabricated of IPS-Empress within the observation
      period. During this time, n = 53 failures were recorded. The remaining
      restorations were observed for a mean period of 18.77 months. The failures were
      mainly attributed to fractures, endodontic problems and cementation errors. The
      last failure was established after 82 months. At this stage, a cumulative
      survival probability of p = 0.81 was registered with a standard error of 0.04. At
      this time, n = 30 restorations were still being observed. Restorations on vital
      teeth (n = 1588) showed 46 failures, with a cumulative survival probability of p
      = 0.82. Restorations performed on non-vital teeth (n = 36) showed seven failures,
      with a cumulative survival probability of p = 0.53. Highly significant
      differences were found between the two groups (p < 0.0001) in a log-rank test. No
      significant difference (p = 0.41) was found between the patients treated by
      students (n = 909) and those treated by qualified dentists (n = 715). Likewise,
      no difference (p = 0.13) was established between the restorations seated with a
      high viscosity cement (n = 295) and those placed with a low viscosity cement (n =
      1329).

PMID- 18051006
TI  - Role of additional retention on marginal adaptation and sealing of large resin
      composite Class II restorations.
AB  - PURPOSE: To compare marginal leakage and gap formation in large resin composite
      Class II cavities with their gingival margins in cementum, using three different
      additional retentions in the proximal box. METHODS: Standardized large Class II
      MOD cavities with gingival margins in cementum were prepared in 40 recently
      extracted molars and divided into four groups according to their retention in the
      proximal box: (G1) no retention; (G2) vertical grooves in the buccal and lingual
      walls; (G3) "pot holes" in the gingival wall and (G4) horizontal grooves in the
      gingival wall. All groups were restored with the incremental technique using the
      same resin composite (QuiXfil, Dentsply) and a bonding agent (Prime Bond NT,
      Dentsply). After polishing, all of the restored teeth were immersed in dye
      solution and submitted to simultaneous cyclic loading. Impressions of the
      gingival margins were made before and after loading, and epoxy resin replicas
      were evaluated for gap formation using a scanning electron microscope. The
      microleakage and gap extension data were evaluated by ANOVA and Tukey's test (p <
      0.05). Gap extension before and after mechanical loading was compared by
      Student's t-test. A correlation analysis was made between the gap extension and
      microleakage (Pearson's correlation test). RESULTS: All groups with additional
      retention (G2 = 0.565, G3 = 0.346 and G4 = 0.078) showed fewer gap formations
      than the control group (G1 = 2.076). Similar results were found for microleakage
      tests. All groups presented an increase in gap extension after loading, with the
      exception of the group with gingival retention grooves (G4). G4 showed the best
      results in relation to both parameters. There was a low correlation between gap
      extension and microleakage.

PMID- 18051007
TI  - Evaluation of curing light distance on resin composite microhardness and
      polymerization.
AB  - This study evaluated the influence of the curing tip distance on cure depth of a
      resin composite by measuring Vickers microhardness and determining the degree of
      conversion by using FT-Raman spectroscopy. The light curing units used were
      halogen (500mW/cm2) and LED (900mW/cm2) at a conventional intensity and an Argon
      laser at 250mW. The exposure time was 40 seconds for the halogen light, 20
      seconds for the LED and 20 and 30 seconds for the Argon laser. The curing tip
      distances of 0, 3, 6 and 9 mm were used and controlled via the use of metal
      rings. The composite was placed in a black matrix in one increment at a thickness
      of 1 mm to 4 mm. The values of microhardness and the degree of conversion were
      analyzed separately by ANOVA (Analysis of Variance) and Tukey test, with a
      significance level set at 5%. Correlations were analyzed using the Pearson test.
      The results obtained conclude that greater tip distances produced a decrease in
      microhardness and degree of conversion values, while increasing the resin
      thickness decreased the microhardness and degree of conversion values. A higher
      correlation between microhardness and the degree of conversion was shown. This
      study suggests that the current light curing units promote a similar degree of
      conversion and microhardness, provided that the resin is not thicker than 1 mm
      and the light source is at a maximum distance of 3 mm from the resin surface.

PMID- 18051008
TI  - Effect of mechanical cycling on the push-out bond strength of fiber posts
      adhesively bonded to human root dentin.
AB  - This study evaluated the effect of mechanical cycling on the bond strength of
      fiber posts bonded to root dentin. The hypotheses examined were that bond
      strength is not changed after fatigue testing and bond strength does not present
      vast variations according to the type of fiber post. Sixty crownless, single
      rooted human teeth were endodontically treated, with the space prepared at 12 mm.
      Thirty specimens received a quartz fiber post (Q-FRC) (DT Light-Post), and the
      remaining 30 specimens received a glass fiber post (G-FRC) (FRC Postec Plus). All
      the posts were resin luted (All Bond+Duolink), and each specimen was embedded in
      a cylinder with epoxy resin. The specimens were divided into six groups: G1- Q
      FRC+no cycling; G2- Q-FRC+20,000 cycles (load: 50N; angle of 450; frequency:
      8Hz); G3- Q-FRC+2,000,000 cycles; G4- G-FRC+no cycling; G5- G-FRC+20,000 cycles;
      G6- G-FRC+2,000,000 cycles. The specimens were cut perpendicular to their long
      axis, forming 2-mm thick disc-samples, which were submitted to the push-out test.
      ANOVA (alpha = .05) revealed that: (a) Q-FRC (7.1 +/- 2.2MPa) and G-FRC (6.9 +/-
      2.1MPa) were statistically similar (p = 0.665); (b) the "no cycling" groups (7.0
      +/- 2.4MPa), "20,000 cycles" groups (7.0 +/- 2.1MPa) and "2,000,000 cycles"
      groups (7.0 +/- 2.0MPa) were statistically similar (p = 0.996). It concluded that
      mechanical cycling did not affect the bond strength of two fiber posts bonded to
      dentin.

PMID- 18051009
TI  - Effects of new formulas of bleaching gel and fluoride application on enamel
      microhardness: an in vitro study.
AB  - This in vitro study evaluated the new formulas of bleaching products and the
      effect of subsequent applications of fluoride on the hardness of enamel during
      and after tooth bleaching. The crowns of 60 extracted intact human molars were
      sectioned longitudinally; the buccal part was embedded in acrylic resin, the
      occlusal part was ground flat, exposing enamel and dentin, and then polished.
      Baseline Knoop microhardness (KHN) of enamel was determined. The specimens were
      then randomly divided into six groups of 10 specimens, and each group was
      assigned to a specific 10% carbamide peroxide (CP) bleaching agent. A:
      Opalescence, B: Opalescence PF (3% potassium nitrate and 0.11% fluoride), C: Nite
      White Excel 3 (ACP), D: Opalescence + F (acidulated phosphate fluoride 1.23%), E:
      Opalescence PF + F, F: Nite White Excel 3 + F. The teeth were bleached for eight
      hours; after each procedure, the specimens were stored in artificial saliva at 37
      degrees C. Immediately after day 21 of bleaching, the specimens in groups D, E
      and F received fluoride 1.23% for five minutes. KHN tests w ere performedbefore
      (baseline = control), during (14, 21) and two weeks (35 days) after the bleaching
      procedure and were statistically compared using ANOVA/Tukey's t-test (alpha <
      0.05). The statistical analysis revealed no significant difference among the
      bleaching materials (p = 0.123). A significant enamel KHN reduction (p < 0.001)
      was observed for all bleaching materials, with no difference among them. Two
      weeks after bleaching, all the groups that received fluoride showed a significant
      increase in microhardness. For the new bleaching formulas, the enamel was
      restored to a value similar to baseline.

PMID- 18051010
TI  - Effect of a ferrule and increased clinical crown length on the in vitro fracture
      resistance of premolars restored using two dowel-and-core systems.
AB  - This study investigated the effect of a crown-lengthening ferrule on the fracture
      resistance of endodontically-treated teeth restored with two dowel-core systems.
      Thirty-two extracted mandibular first premolars were sectioned perpendicular to
      the long axis at a point 1.0 mm occlusal to the buccal cementoenamel junction.
      Following endodontic treatment, the teeth were randomly assigned to four groups:
      cast Ni-Cr alloy dowel-core with no ferrule (Group A1), cast Ni-Cr alloy dowel
      core with 2.0 mm ferrule (Group A2), prefabricated carbon fiber-reinforced dowel
      resin core with no ferrule (Group B1) and carbon fiber-reinforced dowel-resin
      core with 2.0 mm ferrule (Group B2). Each specimen was embedded in a self-cured
      acrylic resin block from 2.0 mm apical to the margins of a cast Ni-Cr alloy
      crown, then loaded at 150 degrees from the long axis in a universal testing
      machine at a crosshead speed of 1.0 mm/minute until fracture. The data were
      recorded and analyzed using ANOVA and Fisher's exact tests, with alpha = 0.05.
      Mean failure loads (kN) for the A1, A2, B1 and B2 Groups were: 1.46 (S.D. 0.45),
      1.07 (0.21), 1.13 (0.30) and 1.02 (0.27). The teeth restored with cast Ni-Cr
      dowel-cores and 2.0 mm ferrules demonstrated significantly lower fracture
      strengths, p = 0.04. There were significant differences in the root fracture
      patterns between the two dowel systems, with the carbon fiber-reinforced dowel
      resin core system, being the less severe p < 0.05. Crown lengthening with a 2.0
      mm apical extended ferrule resulted in reduced fracture strengths for
      endodontically-treated teeth restored using two dowel-core systems and cast metal
      crowns. The carbon fiber-reinforced dowel-resin core system reduced the severity
      of the root fractures.

PMID- 18051011
TI  - Effects of filling techniques on the regional bond strength to lateral walls in
      Class I cavities.
AB  - OBJECTIVES: Using the push-out technique, this study compared the influence of
      different composite insertion techniques in Class I cavities on the regional
      shear bond strength to lateral walls. MATERIALS AND METHOD: Standardized Class I
      cavities were prepared on the occlusal surface of 60 freshly extracted third
      molars, which were randomly assigned to one of five groups (n = 10). The cavities
      were bonded with the self-etch adhesive AdheSE and restored with Tetric Ceram
      resin composite by one of five techniques: G1, incremental technique (four
      oblique layers); G2, flowable composite as liner and bulk technique; G3, bulk
      technique and G4, light cone technique. The total-etch adhesive (Single Bond) and
      incremental technique were used as the control procedure. Each specimen was
      sectioned perpendicular to the long axis of the tooth in 1 mm-thick dentin
      slices. A push-out test was performed to measure regional bond strengths and
      identify the type of failure. Two additional teeth per group were prepared for
      the morphological interface study using scanning electron microscopy. RESULTS:
      Differences between the groups were tested by one-way ANOVA and Scheffe post hoc
      test (F = 29.635, p < 0.001). The highest shear bond strength values were
      obtained with the incremental technique, regardless of the adhesive used.
      Significant differences in bond strength to superficial and deep dentin were only
      found when a total-etch adhesive was used (Single Bond). CONCLUSIONS: Use of the
      incremental technique with total-etch or self-etch adhesives is the most
      effective method of inserting resin-based composites in large Class I cavities.

PMID- 18051012
TI  - Effect of different fluoridation regimes on the microhardness of bleached enamel.
AB  - PURPOSE: This in vitro study evaluated the effects of toothpaste fluoridation and
      toothpaste plus gel fluoridation and influence of the time period of fluoride gel
      application on the microhardness of bleached enamel. METHODS: Ninety bovine
      enamel samples were distributed among nine groups (A-I), each having 10 samples.
      Half of each surface was bleached with 10% carbamide peroxide gel (8 hours/daily)
      for 14 days, while the remaining surface was not bleached and served as the
      control. Groups A-H were fluoridated with toothpaste twice daily throughout the
      experiment (42 days) and assigned to fluoride gel treatment during the pre
      bleaching period (14 days), during the bleaching period and/or during the post
      bleaching period (14 days): A: prior, B: during, C: post, D: prior+during, E:
      during+post, F: prior+post, G: prior+during+post, H: no gel. Group I was neither
      fluoridated by toothpaste nor gel. The Knoop microhardness (KHN) of each specimen
      was determined at baseline, after pre-bleaching (day 14), after bleaching (day
      28) and after post-bleaching (day 42). Statistical analysis of the percentage of
      change at baseline KHN was performed by ANOVA and t-test (p < 0.05). RESULTS:
      Bleaching led to a significant decrease of KHN in Group I (unfluoridated)
      compared to Groups A-H, where microhardness did not fall below baseline values.
      Fluoridation treatment in Groups A-H increased microhardness in bleached and
      unbleached samples, but additional supplementation of fluoride gel in Groups A-G
      was not superior to toothpaste fluoridation only (H). After the post-bleaching
      period, the microhardness of the bleached and unbleached surfaces was not
      significantly different in Groups A-H. CONCLUSION: Regular toothpaste
      fluoridation prevents microhardness loss due to bleaching treatment in vitro. The
      additional supplementation of fluoride gel did not enhance the beneficial effect
      of toothpaste fluoridation, and microhardness was not influenced by the time
      period of gel fluoridation.

PMID- 18051013
TI  - The effect of curing units and staining solutions on the color stability of resin
      composites.
AB  - This study investigated the effects of two different light curing units and two
      staining solutions on the color stability of a hybrid composite and a nanohybrid
      composite after different immersion periods. Thirty disk-shaped specimens (10 mm
      in diameter, 2-mm thick) were fabricated for each of the resin composites,
      Clearfil AP-X and Filtek Supreme. The specimens were randomly divided into two
      groups according to the curing unit used: Group I specimens (n = 15) were cured
      with a quartz-tungsten-halogen (QTH) light for 40 seconds, and Group II specimens
      (n = 15) were cured with a light-emitting diode (LED) unit in standard mode for
      40 seconds. The specimens were incubated in 100% humidity at 37 degrees C for 24
      hours. Then, the baseline color values (L*, a*, b*) of each specimen were
      measured with a spectrophotometer according to the CIELab color scale. After
      baseline color measurements, five randomly selected specimens from each group
      (Groups I and II) were immersed in one of two staining solutions (tea or coffee)
      or distilled water (control). After 1, 7 and 30 days of immersion, the color
      values of each specimen were remeasured and the color change value (deltaE*ab)
      calculated. Color changes caused by immersion in tea and coffee for 30 days were
      only perceptible in the Clearfil AP-X specimens cured with QTH or LED. In the
      Filtek Supreme specimens, coffee perceptibly stained the teeth after all
      immersion periods and tea stained after 30 days. Polymerization with QTH or LED
      did not cause any significant difference in the color stability of Clearfil AP-X
      or Filtek Supreme. While there were no significant differences between staining
      solutions in the Clearfil AP-X specimens cured with LED after one and seven days
      of storage and one day of storage in the QTH cured specimens, significant
      differences were observed between water and coffee after seven days of storage.
      In the Filtek Supreme specimens cured with QTH or LED, there were statistically
      significant differences between the staining solutions after one and seven days
      of storage. After 30 days of storage, no significant difference was found between
      tea and coffee in either resin composite cured with QTH or LED. The effect of the
      staining solutions (tea, coffee) on color changes in composites was immersion
      time and resin-material dependent.

PMID- 18051014
TI  - The effect of surface preparation and luting agent on bond strength to a
      zirconium-based ceramic.
AB  - OBJECTIVES: To investigate the bond strength of modern "self-adhesive" resin
      cements to a zirconium-based dental ceramic following different surface
      preparations and storage conditions. METHODS: The surface of zirconium-based
      ceramic discs (12 x 2 mm) were either left untreated, prepared using alumina grit
      blasting or tribochemical treatment. Resin composite cylinders were bonded to
      ceramic specimens using Panavia-F, RelyX Unicem or Maxcem resin cements. The
      shear bond strength of specimens (n = 10) was tested "dry," following 24-hour
      water immersion or a thermocycling regime. RESULTS: For each surface preparation,
      a significant reduction in bond strength following 24-hour water immersion and
      thermocycling compared to "dry" storage conditions was identified for both
      Panavia-F and Maxcem. However, Unicem specimens exhibited statistically similar
      SBS values for tribochemically-treated specimens stored dry following 24-hour
      water immersion or thermocycling (11.7 +/- 1.3, 14.1 +/- 6.3 and 11.7 +/- 4.9
      MPa, respectively) (p > 0.05). No significant differences in bond strength were
      identified for Panavia-F or Unicem specimens for any surface preparation
      following the thermocycling regime (p > 0.05). In contrast, for each surface
      preparation following thermocycling (p < 0.001), Maxcem exhibited a significant
      decrease in SBS compared with Panavia-F and Unicem specimens. CONCLUSIONS: The
      pre-treatment of a zirconium-based ceramic surface with grit-blasting and
      tribochemical treatment improves the bond strength of resin cements. Following
      "wet" storage conditions, Panavia-F and Unicem demonstrated superior bond
      strength compared with Maxcem. Differences in ceramic surface preparation and the
      chemistry of resin cements will affect the nature of the bonding mechanism and
      durability of the adhesive layer.

PMID- 18051015
TI  - Hospice heritage. Introduction.

PMID- 18051016
TI  - Patient care: past, present, and future.
AB  - The 40 years since St Christopher's Hospice opened has witnessed a burgeoning
      international interest in palliative care. Its key characteristics comprise a
      focus on the whole-person (physical, psychological, social, and spiritual),
      patient-centeredness (partnership with and empowerment of the patient and
      family), openness and honesty in communication, an acceptance of the
      inevitability of death coupled with improvement in the quality of life, multi
      professional teamwork integrated with community (volunteer) involvement. Although
      much has been achieved, much remains to be done. Both in resource-poor countries
      and in more wealthy ones, the scope of palliative care has changed. Initially in
      the United Kingdom, palliative care was mostly limited to cancer patients but now
      strenuous efforts are being made to extend coverage to other patient groups,
      e.g., those with end-stage heart disease or renal failure. In India, with a
      dearth of chronic care facilities, palliative care services increasingly embrace
      those with chronic disability as well as progressive end-stage disease. In Sub
      Saharan Africa, the devastating impact of AIDS is having a major impact on the
      development and delivery of palliative care. To maximize the benefits of limited
      financial and other resources, a strategic approach is necessary. The World
      Health Organization emphasizes three essential foundation measures: health
      service policy, public awareness and professional education, and drug
      availability. However, at the end of the day, if we are truly to honor Cicely
      Saunders, palliative care must remain a movement with momentum, combining
      creative charisma with inevitable bureaucratic routinization.

PMID- 18051017
TI  - Family care before and after bereavement.
AB  - Distress reverberates throughout the family during palliative care and
      bereavement, inviting consideration of a family-centered model of care. Targeting
      families thought to be "at risk" has merit. The Family Focused Grief Therapy
      model was tested in a randomized controlled trial of 81 families (353
      individuals) and bereavement outcome is reported here for treatment completers
      compared to controls. There were no significant baseline differences between
      treatment completers and non-completers. Significant reduction in distress
      occurred at 13 months post death for the families completing treatment, with
      further improvements for the 10% of individuals most distressed at baseline. A
      preventive model of family-centered care applied to those at greatest risk is
      meritorious and in keeping with the aspirations of Cicely Saunders for improving
      the quality of hospice care.

PMID- 18051018
TI  - Spirituality and the care of patients at the end-of-life: an essential component
      of care.
AB  - Spirituality is an essential component of the care of patients with serious
      illness and those that are dying. Dame Cicely Saunders developed the hospice
      movement based on the biopsychosocialspiritual model of care, in which all four
      dimensions are important in the care of patients. Of all the models of care,
      hospice and palliative care recognize the importance of spiritual issues in the
      care of patients and their families. The National Consensus Project Guidelines
      for Quality Palliative Care, in the United States, provides specific
      recommendations about all domains of care including the spiritual domain, which
      is recognized as a critical component of care (The National Consensus Project for
      Quality Palliative Care www.nationalconsensusproject.org). Studies indicate that
      the majority of patients would like their spiritual issues addressed, yet find
      that their spiritual needs are not being met by the current system of care.
      Interestingly, spirituality is the one dimension that seems to get slightly less
      emphasis than the biopsychosocial dimensions of care. Some reasons may include
      the difficulty with definitions of spirituality for clinical and research
      purposes, the time constraints and financial burdens in the current healthcare
      system in the United States, and the lack of uniform training for all healthcare
      professionals. Yet, there are theoretical and ethical frameworks that support
      spiritual care as well as some educational models in spirituality and health that
      have been successful in medical education in the United States. Spirituality can
      be seen as the essential part of the humanity of all people. It is at its root,
      relational and thus forms the basis of the altruistic care healthcare
      professionals are committed to. Spirituality has to do with respecting the
      inherent value and dignity of all persons, regardless of their health status. It
      is the part of humans that seeks healing, particularly in the midst of suffering.
      Spiritual care models are based on an intrinsic aspect that calls for
      compassionate presence to patients as well as an extrinsic component where
      healthcare professionals address spiritual issues with patients and their loved
      ones. Currently in the healthcare system, evidence-base models are the criteria
      for practice recommendations. Yet, spirituality may not be amenable entirely to
      strict evidence-base criteria. As hospice and palliative care continues to
      develop as a field, healthcare professionals are challenged to think of ways to
      advocate for and include the spiritual dimension of care.

PMID- 18051019
TI  - Spreading the word ... hospice information systems.
AB  - The rapid spread of Saunders' thinking across the world has been facilitated by
      the Hospice Information service and library at St Christopher's Hospice which she
      helped to create and further enhanced by Help the Hospices. We have set this
      article in the context of the Web and other information systems as they are
      developing today. "Connecting people" and "collecting people's experiences" were
      terms often used by Cicely Saunders when she described the work of Hospice
      Information, a service that has in some measure contributed to the rapid spread
      of her thinking across the world and which is currently in close contact with
      palliative care workers in over 120 countries. Connecting--or networking--putting
      people and organizations in touch with each other for mutual benefit and
      collecting and disseminating people's experiences are central to our work as a
      U.K. and international resource on hospice and palliative care for professionals
      and the public. Add to these the crucial role of information provision and
      advocacy for patients, carers, and health professionals alike and we hope that
      you may begin to appreciate how our respective organizations have contributed to
      the spread of Cicely Saunders' vision.

PMID- 18051020
TI  - St Christopher's and the future.
AB  - The founding vision of St Christopher's Hospice was based on a recognition that
      permeating mainstream health care services would be essential and an emphasis on
      an adaptable philosophy rather than a building. Today, demographic and disease
      related changes mean that need and demand for end-of-life care will inevitably
      outstrip professional and financial resource. Hospices must engage with the
      development of cost-effective models of service delivery and rational planning.
      Only partnership working with the National Health Service, care homes, and others
      will ensure that appropriate care is available to everyone wherever the bed in
      which they die, regardless of diagnosis. Only collaboration and active engagement
      will ensure that future strategy in end-of-life care retains the original insight
      that its focus rightly includes not only patients but also the social context
      that will be affected by their death. Cost and patient choice dictate an emphasis
      on care at home. Health-promoting, public education and family-focused strategies
      will be essential. At a pivotal moment for the delivery of health care generally,
      hospices can play a vital part by marrying the role of "insistent conscience" of
      the health care service with continued cost-effective clinical innovation.

PMID- 18051021
TI  - Palliative medicine in Britain.
AB  - In Britain, Palliative Medicine was recognized as a subspecialty of Internal
      Medicine exactly 20 years after Cicely Saunders founded St Christopher's, at
      exactly the same time that government was at last recognizing the worth and the
      needs of general practice. Both had far-reaching effects and implications for
      patients, doctors, and the future of medicine. For Palliative Medicine it meant
      units wishing to train specialists going through a rigorous selection process;
      the development of an equally rigorous training program for the doctors who had
      already gained a higher qualification before starting Palliative Medicine,
      demonstrating the need for and benefits of palliative medicine to the sceptics in
      the profession and, now, continuing to recruit the staff for the steadily
      increasing number of new services. Today there are more Palliative Medicine
      consultants/specialists than there are oncologists and neurologists combined,
      with Hospital Palliative Care Teams in every major hospital and cancer center.
      With nine Chairs in Palliative Medicine, there is now a drive for research and
      professional education. The specialty faces major challenges, however, ranging
      from training to care for patients with non-malignant disease to enabling
      patients to die in the place of their choice-something that rarely happens today;
      from defining what is distinctive or unique about palliative medicine to
      clarifying the respective place of general practice and the specialty. Most would
      agree that the biggest challenge for the young, thriving specialty is how to
      share its principles with other doctors wherever they work.

PMID- 18051022
TI  - Development of hospice and palliative care in the United States.
AB  - More than 30 years have passed since palliative care was introduced in the United
      States, and what began as a small rebellion has evolved into a fairly large
      health care industry. Although the palliative care movement has considerably
      improved the care given to those at the end of life, many challenges remain for
      palliative care providers in the United States. This article discusses the
      history of hospice and palliative care in the United States, the Medicare Hospice
      Benefit, the growth of hospice and palliative care, and challenges such as the
      need for regulatory change, workforce issues, improving access to care, and
      improving the quality of palliative care.

PMID- 18051023
TI  - End-of-life care around the world: achievements to date and challenges remaining.
AB  - From the moment her interest in terminal care was awakened, Cicely Saunders was
      alert to the international dimensions of the subject. Her first patient in the
      late 1940s was an emigre Polish Jew dying alone and in isolation in a busy London
      hospital. Her letters from the 1950s onwards show an unquenchable thirst for new
      knowledge and a span of contacts and communications that was global in its reach.
      By the early 1960s, she was making fact-finding visits to the United States and
      Europe. Even before it opened to patients, St Christopher's Hospice was a beacon
      of inspiration to like-minded colleagues from many countries, eager to see how
      the model of practice was being operationalized and--more important still--how it
      could be adapted and modified in other settings. In the later years of her life,
      Cicely Saunders remained in contact with colleagues all over the world. She wrote
      introductions to numerous textbooks and collections; recorded interviews that
      were broadcast at international conferences; harnessed her name and energies to
      major efforts to promote palliative care globally; and, to the very end, served
      as a source of inspiration to palliative care activists, policy makers,
      educators, and researchers. As this special issue of the journal demonstrates so
      eloquently, that legacy lives on.

PMID- 18051024
TI  - Hospice: achievements, legacies, and challenges.

PMID- 18051025
TI  - Reversible airway obstruction in casual and competitive athletes.

PMID- 18051026
TI  - Primary ectopic breast cancer of the axilla.
AB  - Ectopic breast cancer in the axilla may be misdiagnosed as a lipoma, enlarged
      lymph node, sebaceous cyst, or as hidradenitis suppurativa. We report a case of
      ectopic breast cancer and review the literature regarding the pathophysiology,
      prognosis and treatment of this disease. The case demonstrates how it is
      imperative that one include cancer in the differential diagnosis when evaluating
      an axillary mass.

PMID- 18051027
TI  - Unusual cause of shoulder pain in a 15-year-old male.

PMID- 18051028
TI  - A cooperative life saving program of physicians, hospitals, and health
      departments in the field of accident prevention and control: A poison control
      program for Connecticut. 1957.

PMID- 18051029
TI  - On mentoring--an opportunity for the "seniors" among us.

PMID- 18051030
TI  - Response to Dr. Arnold D. Newman's comments on radiology then and now.

PMID- 18051031
TI  - CPD, an effective means of professional development...or is it?

PMID- 18051032
TI  - The criminal use of improvised and re-activated firearms in Great Britain and
      Northern Ireland.
AB  - Following the Hungerford Massacre the British Government imposed additional
      strict firearms legislation in 1988 that involved several classes of arms being
      placed into the prohibited category. By way of compensation a scheme was
      introduced to allow the unrestricted possession and transfer of the newly
      prohibited arms, other firearms and "prohibited weapons", if de-activated to a
      standard acceptable to the Secretary of State. Approved standards for firearm de
      activation were drawn up in 1989. The inspection of the de-activated arms was
      devolved to the two Gun Barrel Proof Houses at London and Birmingham, as
      otherwise the task of inspecting the thousands of guns involved would have
      overloaded the firearms section at the Huntingdon Forensic Science Service
      Laboratory, who were already dealing with criminal firearms cases submitted by 41
      of the 43 police forces throughout England and Wales, as well as providing
      technical assistance to the Home Office and Government Ministers. Members of the
      Gun Trade made representations to the Minister involved during the initial stages
      of setting up the official de-activation standards. This resulted in some measure
      of compromise in the range and nature of the de-activation requirements. Although
      it was clear that some individuals possessing the necessary skill and equipment
      might attempt to restore the odd weapon to a working condition, the scheme
      appeared to work reasonably well for the next few years. However, over the
      passage of time, criminal casework submissions to the Huntingdon Laboratory from
      industrial city areas along the M62 corridor of northern England revealed a
      steadily growing trend in the use of re-activated arms, which in a significant
      number of cases involved the use of fully automatic weapons. At first, the nature
      of the re-activation processes used to restore these arms was quite crude.
      However, with the passage of time a steady improvement in the machining and
      welding skills used by the some of the culprits involved became more and more
      apparent, as was a move by them to bulk restoration. The use of restored arms in
      serious and often drug related crime, spread to the other mainland British
      cities, and eventually to Northern Ireland. More rigorous de-activation standards
      were introduced in 1995 to help counter this perceived threat, particularly in
      respect of handguns and full-automatic weapons. Blank cartridge pistols and air
      cartridge pistols were also being modified to allow their use with bulleted
      ammunition in the commission of criminal offences. As a result all air cartridge
      guns were placed into the prohibited weapons category in 2003, and the possession
      of imitation firearms in a public place without good reason, also became an
      offence. The Government is now considering further legislation, which will affect
      the sale of replica firearms and cartridge reloading equipment and materials.

PMID- 18051033
TI  - Effectiveness of contamination prevention procedures in a trace explosives
      laboratory.
AB  - The effectiveness of a number of the explosives contamination prevention controls
      that are adopted within the Forensic Explosives Laboratory (FEL) principal trace
      laboratory has been scrutinised. Within the trace laboratory, rigorous procedures
      for processing forensic swab samples for traces of organic explosives are
      routinely adopted by forensic scientists. In order to demonstrate the
      effectiveness of these procedures, and the principle of separating the sample
      from the laboratory and the forensic scientist, explosives-free swab samples and
      appropriate controls have been processed, in accordance with trace laboratory
      procedures, in several explosives contaminated environments. In all cases, no
      explosives were detected in the post-processing samples, demonstrating that the
      contamination prevention procedures are effective, robust and fit-for-purpose.

PMID- 18051034
TI  - The use of grain size distribution analysis of sediments and soils in forensic
      enquiry.
AB  - The use of grain size distribution analysis in forensic enquiry was investigated
      with reference to four forensic case studies which contained the type of sample
      restraints and limitations often encountered in criminal case work. The problems
      of the comparison of trace and bulk samples are outlined and the need for
      multiple sample analysis is highlighted. It was found that the problems of soil
      analysis, particularly when the soil was recovered from anthropogenic sources,
      focused on the lack of identification of pre-, syn- and post-forensic event
      mixing of materials, thus obscuring the recognition of false-negative or false
      positive exclusions between samples. It was found that grain size distribution
      analysis was a useful descriptive tool but it was concluded that if it were to be
      used in any other manner the derived results should be treated with great
      caution. The statistical analyses of these data did not improve the quality of
      the interpretation of the results.

PMID- 18051035
TI  - Fingerprint recovery from human skin surfaces.
AB  - A study was conducted to investigate whether certain dactyloscopic powders and
      reagents can recover latent fingerprints on human skin surfaces. Four fingerprint
      powders, Magnetic Jet Black, Magnetic Silver, Silver Special, Swedish Black, and
      two other methods, cyanoacrylate fuming (CA) and Ruthenium tetroxide (RTX), were
      used. Having examined skin surfaces with a forensic light source, we observed
      that the fingerprint impressions remained visible up to 15 min after
      intentionally placing them on the skin surface of living subjects and dead
      bodies. Finger marks were recovered and positive results were achieved with
      Magnetic Black and Swedish Black powder on living subjects. On dead bodies finger
      marks treated with cyanoacrylate were visible but those treated with RTX, Swedish
      Black and Magnetic Jet Black powder were useful for potential comparison. On dead
      bodies best results were obtained with RTX method.

PMID- 18051036
TI  - Sediment fingerprints: a forensic technique using quartz sand grains--a response.

PMID- 18051037
TI  - Geodesic-loxodromes for diffusion tensor interpolation and difference
      measurement.
AB  - In algorithms for processing diffusion tensor images, two common ingredients are
      interpolating tensors, and measuring the distance between them. We propose a new
      class of interpolation paths for tensors, termed geodesic-loxodromes, which
      explicitly preserve clinically important tensor attributes, such as mean
      diffusivity or fractional anisotropy, while using basic differential geometry to
      interpolate tensor orientation. This contrasts with previous Riemannian and Log
      Euclidean methods that preserve the determinant. Path integrals of tangents of
      geodesic-loxodromes generate novel measures of over-all difference between two
      tensors, and of difference in shape and in orientation.

PMID- 18051038
TI  - Quantification of measurement error in DTI: theoretical predictions and
      validation.
AB  - The presence of Rician noise in magnetic resonance imaging (MRI) introduces
      systematic errors in diffusion tensor imaging (DTI) measurements. This paper
      evaluates gradient direction schemes and tensor estimation routines to determine
      how to achieve the maximum accuracy and precision of tensor derived measures for
      a fixed amount of scan time. We present Monte Carlo simulations that quantify the
      effect of noise on diffusion measurements and validate these simulation results
      against appropriate in-vivo images. The predicted values of the systematic and
      random error caused by imaging noise are essential both for interpreting the
      results of statistical analysis and for selecting optimal imaging protocols given
      scan time limitations.

PMID- 18051039
TI  - In-utero three dimension high resolution fetal brain diffusion tensor imaging.
AB  - We present a methodology to achieve 3D high resolution in-utero fetal brain DTI
      that shows excellent ADC as well as promising FA maps. After continuous DTI
      scanning to acquire a repeated series of parallel slices with 15 diffusion
      directions, image registration is used to realign the images to correct for fetal
      motion. Once aligned, the diffusion images are treated as irregularly sampled
      data where each voxel is associated with an appropriately rotated diffusion
      direction, and used to estimate the diffusion tensor on a regular grid. The
      method has been tested successful on eight fetuses and has been validated on
      adults imaged at 1.5T.

PMID- 18051040
TI  - Real-time MR diffusion tensor and Q-ball imaging using Kalman filtering.
AB  - Magnetic resonance diffusion imaging (dMRI) has become an established research
      tool for the investigation of tissue structure and orientation. In this paper, we
      present a method for real time processing of diffusion tensor and Q-ball imaging.
      The basic idea is to use Kalman filtering framework to fit either the linear
      tensor or Q-ball model. Because the Kalman filter is designed to be an
      incremental algorithm, it naturally enables updating the model estimate after the
      acquisition of any new diffusion-weighted volume. Processing diffusion models and
      maps during ongoing scans provides a new useful tool for clinicians, especially
      when it is not possible to predict how long a subject may remain still in the
      magnet.

PMID- 18051041
TI  - Finsler tractography for white matter connectivity analysis of the cingulum
      bundle.
AB  - In this paper, we present a novel approach for the segmentation of white matter
      tracts based on Finsler active contours. This technique provides an optimal
      measure of connectivity, explicitly segments the connecting fiber bundle, and is
      equipped with a metric which is able to utilize the directional information of
      high angular resolution data. We demonstrate the effectiveness of the algorithm
      for segmenting the cingulum bundle.

PMID- 18051042
TI  - Segmentation of myocardial volumes from real-time 3D echocardiography using an
      incompressibility constraint.
AB  - Real-time three-dimensional (RT3D) echocardiography is a new imaging modality
      that presents the unique opportunity to visualize the complex three-dimensional
      (3-D) shape and the motion of left ventricle (LV) in vivo. To take advantage of
      this opportunity, automatic segmentation of LV myocardium is essential. While
      there are a variety of efforts on the segmentation of LV endocardial (ENDO)
      boundaries, the segmentation of epicardial (EPI) boundaries is still problematic.
      In this paper, we present a new approach of coupled-surfaces propagation to
      address this problem. Our method is motivated by the idea that the volume of the
      myocardium is close to being constant during a cardiac cycle and takes this tight
      coupling as an important constraint. We employ two surfaces, each driven by the
      image-derived information that takes into account the ultrasound physics by
      modeling speckle using shifted Rayleigh distribution while maintaining the
      coupling. By evolving two surfaces simultaneously, the final representation of
      myocardium is thus achieved. Results from 328 sets of RT3D echocardiographic data
      are evaluated against the outlines of three observers. We show that the results
      from automatic segmentation are comparable to those from manual segmentation.

PMID- 18051043
TI  - Localized shape variations for classifying wall motion in echocardiograms.
AB  - To quantitatively predict coronary artery diseases, automated analysis may be
      preferred to current visual assessment of left ventricular (LV) wall motion. In
      this paper, a novel automated classification method is presented which uses shape
      models with localized variations. These sparse shape models were built from four
      chamber and two-chamber echocardiographic sequences using principal component
      analysis and orthomax rotations. The resulting shape parameters were then used to
      classify local wall-motion abnormalities of LV segments. Various orthomax
      criteria were investigated. In all cases, higher classification correctness was
      achieved using significantly less shape parameters than before rotation. Since
      pathologies are typically spatially localized, many medical applications
      involving local classification should benefit from orthomax parameterizations.

PMID- 18051044
TI  - Image guidance of intracardiac ultrasound with fusion of pre-operative images.
AB  - This paper presents a method for registering 3D intracardiac echo (ICE) to pre
      operative images. A magnetic tracking sensor is integrated on the ICE catheter
      tip to provide the 3D location and orientation. The user guides the catheter into
      the patient heart to acquire a series of ultrasound images covering the anatomy
      of the heart chambers. An automatic intensity-based registration algorithm is
      applied to align these ultrasound images with pre-operative images. One of the
      important applications is to help electrophysiology doctors to treat complicated
      atrial fibrillation cases. After registration, the doctor can see the position
      and orientation of the ICE catheter and other tracked catheters inside the heart
      anatomy in real time. The image guidance provided by this technique may increase
      the ablation accuracy and reduce the amount of time for the electrophysiology
      procedures. We show successful image registration results from animal
      experiments.

PMID- 18051045
TI  - 3D reconstruction of internal organ surfaces for minimal invasive surgery.
AB  - While Minimally Invasive Surgery (MIS) offers great benefits to patients compared
      with open surgery surgeons suffer from a restricted field-of-view and obstruction
      from instruments. We present a novel method for 3D reconstruction of soft tissue,
      which can provide a wider field-of-view with 3D information for surgeons,
      including restoration of missing data. The paper focuses on the use of Structure
      from Motion (SFM) techniques to solve the missing data problem and application of
      competitive evolutionary agents to improve the robustness to missing data and
      outliers. The method has been evaluated with synthetic data, images from a
      phantom heart model, and in vivo MIS image sequences using the da Vinci
      telerobotic surgical system.

PMID- 18051046
TI  - Cardiolock: an active cardiac stabilizer. First in vivo experiments using a new
      robotized device.
AB  - Off-pump Coronary Artery Bypass Grafting (CABG) is still today a technically
      difficult procedure. In fact, the mechanical stabilizers used to locally suppress
      the heart excursion have been demonstrated to exhibit significant residual
      motion. We therefore propose a novel active stabilizer which is able to
      compensate for this residual motion. The interaction between the heart and a
      mechanical stabilizer is first assessed in vivo on an animal model. Then, the
      principle of active stabilization, based on the high speed vision-based control
      of a compliant mechanism, is presented. In vivo experimental results are given
      using a prototype which structure is compatible with a minimally invasive
      approach.

PMID- 18051047
TI  - Automated segmentation of the liver from 3D CT images using probabilistic atlas
      and multi-level statistical shape model.
AB  - An atlas-based automated liver segmentation method from 3D CT images is
      described. The method utilizes two types of atlases, that is, the probabilistic
      atlas (PA) and statistical shape model (SSM). Voxel-based segmentation with PA is
      firstly performed to obtain a liver region, and then the obtained region is used
      as the initial region for subsequent SSM fitting to 3D CT images. To improve
      reconstruction accuracy especially for largely deformed livers, we utilize a
      multi-level SSM (ML-SSM). In ML-SSM, the whole shape is divided into patches, and
      principal component analysis is applied to each patches. To avoid the
      inconsistency among patches, we introduce a new constraint called the
      adhesiveness constraint for overlap regions among patches. In experiments, we
      demonstrate that segmentation accuracy improved by using the initial region
      obtained with PA and the introduced constraint for ML-SSM.

PMID- 18051048
TI  - Statistical and topological atlas based brain image segmentation.
AB  - This paper presents a new atlas-based segmentation framework for the delineation
      of major regions in magnetic resonance brain images employing an atlas of the
      global topological structure as well as a statistical atlas of the regions of
      interest. A segmentation technique using fast marching methods and tissue
      classification is proposed that guarantees strict topological equivalence between
      the segmented image and the atlas. Experimental validation on simulated and real
      brain images shows that the method is accurate and robust.

PMID- 18051049
TI  - A boosted segmentation method for surgical workflow analysis.
AB  - As demands on hospital efficiency increase, there is a stronger need for
      automatic analysis, recovery, and modification of surgical workflows. Even though
      most of the previous work has dealt with higher level and hospital-wide workflow
      including issues like document management, workflow is also an important issue
      within the surgery room. Its study has a high potential, e.g., for building
      context-sensitive operating rooms, evaluating and training surgical staff,
      optimizing surgeries and generating automatic reports. In this paper we propose
      an approach to segment the surgical workflow into phases based on temporal
      synchronization of multidimensional state vectors. Our method is evaluated on the
      example of laparoscopic cholecystectomy with state vectors representing tool
      usage during the surgeries. The discriminative power of each instrument in regard
      to each phase is estimated using AdaBoost. A boosted version of the Dynamic Time
      Warping (DTW) algorithm is used to create a surgical reference model and to
      segment a newly observed surgery. Full cross-validation on ten surgeries is
      performed and the method is compared to standard DTW and to Hidden Markov Models.

PMID- 18051050
TI  - Detection of spatial activation patterns as unsupervised segmentation of fMRI
      data.
AB  - In functional connectivity analysis, networks of interest are defined based on
      correlation with the mean time course of a user-selected 'seed' region. In this
      work we propose to simultaneously estimate the optimal representative time
      courses that summarize the fMRI data well and the partition of the volume into a
      set of disjoint regions that are best explained by these representative time
      courses. Our approach offers two advantages. First, is removes the sensitivity of
      the analysis to the details of the seed selection. Second, it substantially
      simplifies group analysis by eliminating the need for a subject-specific
      threshold at which correlation values are deemed significant. This unsupervised
      technique generalizes connectivity analysis to situations where candidate seeds
      are difficult to identify reliably or are unknown. Our experimental results
      indicate that the functional segmentation provides a robust, anatomically
      meaningful and consistent model for functional connectivity in fMRI.

PMID- 18051051
TI  - Robotic assistance for ultrasound guided prostate brachytherapy.
AB  - We present a robotically assisted prostate brachytherapy system and test results
      in training phantoms. The system consists of a transrectal ultrasound (TRUS) and
      a spatially co-registered robot integrated with an FDA-approved commercial
      treatment planning system. The salient feature of the system is a small parallel
      robot affixed to the mounting posts of the template. The robot replaces the
      template interchangeably and uses the same coordinate system. Established
      clinical hardware, workflow and calibration are left intact. In these
      experiments, we recorded the first insertion attempt without adjustment. All
      clinically relevant locations were reached. Non-parallel needle trajectories were
      achieved. The pre-insertion transverse and rotational errors (measured with
      Polaris optical tracker relative to the template's coordinate frame) were 0.25mm
      (STD = 0.17mm) and 0.75 degrees (STD = 0.37 degrees). The needle tip placement
      errors measured in TRUS were 1.04mm (STD = 0.50mm). The system is in Phase-I
      clinical feasibility and safety trials, under Institutional Review Board
      approval.

PMID- 18051053
TI  - Simulation and fully automatic multimodal registration of medical ultrasound.
AB  - The fusion of 3D freehand ultrasound with CT and CTA has benefits for a variety
      of clinical applications, however a lot of manual work is usually required for
      correct registration. We developed new methods that allow one to simulate medical
      ultrasound from CT in real-time, reproducing the majority of ultrasonic imaging
      effects. The second novelty is a robust similarity measure that assesses the
      correlation of a combination of multiple signals extracted from CT with
      ultrasound, without knowing the influence of each signal. This serves as the
      foundation of a fully automatic registration, which aligns a freehand ultrasound
      sweep with the corresponding 3D modality using a rigid or an affine
      transformation model, without any manual interaction. We also present the used
      initialization, global and local parameter optimization schemes, and validation
      on abdominal CTA and ultrasound imaging of 10 patients.

PMID- 18051052
TI  - Closed-loop control in fused MR-TRUS image-guided prostate biopsy.
AB  - Multi-modality fusion imaging for targeted prostate biopsy is difficult because
      of prostate motion during the biopsy procedure. A closed-loop control mechanism
      is proposed to improve the efficacy and safety of the biopsy procedure, which
      uses real-time ultrasound and spatial tracking as feedback to adjust the
      registration between a preoperative 3D image (e.g. MRI) and real-time ultrasound
      images. The spatial tracking data is used to initialize the image-based
      registration between intraoperative ultrasound images and a preoperative
      ultrasound volume. The preoperative ultrasound volume is obtained using a 2D
      sweep and manually registered to the MRI dataset before the biopsy procedure. The
      accuracy of the system is 2.3 +/- 0.9 mm in phantom studies. The results of
      twelve patient studies show that prostate motion can be effectively compensated
      using closed-loop control.

PMID- 18051054
TI  - Improving the contrast of breast cancer masses in ultrasound using an
      autoregressive model based filter.
AB  - The assessment and diagnosis of breast cancer with ultrasound is a challenging
      problem due to the low contrast between cancer masses and benign tissue. Due to
      this low contrast it has proven to be difficult to achieve reliable segmentation
      results on breast cancer masses. An autoregressive model has been employed to
      filter out of the backscattered RF-signal from a tissue harmonic image which is
      not degraded by harmonic leakage. Measurements on the filtered image have shown a
      significant (up to 45%) increase in contrast between cancer masses and benign
      tissue.

PMID- 18051055
TI  - Outlier rejection for diffusion weighted imaging.
AB  - This paper introduces an outlier rejection and signal reconstruction method for
      high angular resolution diffusion weighted imaging. The approach is based on the
      thresholding of Laplacian measurements over the sphere of the apparent diffusion
      coefficient profiles defined for a given set of gradient directions. Exemplary
      results are presented.

PMID- 18051056
TI  - Generating fiber crossing phantoms out of experimental DWIs.
AB  - In Diffusion Tensor Imaging (DTI), differently oriented fiber bundles inside one
      voxel are incorrectly modeled by a single tensor. High Angular Resolution
      Diffusion Imaging (HARDI) aims at using more complex models, such as a two-tensor
      model, for estimating two fiber bundles. We propose a new method for creating
      experimental phantom data of fiber crossings, by mixing the DWI-signals from high
      FA-regions with different orientation. The properties of these experimental
      phantoms approach the conditions of real data. These phantoms can thus serve as a
      'ground truth' in validating crossing reconstruction algorithms. The angular
      resolution of a dual tensor model is determined using series of crossings,
      generated under different angles. An angular resolution of 0.67pi was found in
      data scanned with a diffusion weighting parameter b = 1000 s/mm2. This resolution
      did not change significantly in experiments with b = 3000 and 5000 s/mm2, keeping
      the scanning time constant.

PMID- 18051057
TI  - Motion and positional error correction for cone beam 3D-reconstruction with
      mobile C-arms.
AB  - CT-images acquired by mobile C-arm devices can contain artefacts caused by
      positioning errors. We propose a data driven method based on iterative 3D
      reconstruction and 2D/3D-registration to correct projection data inconsistencies.
      With a 2D/3D-registration algorithm, transformations are computed to align the
      acquired projection images to a previously reconstructed volume. In an iterative
      procedure, the reconstruction algorithm uses the results of the registration
      step. This algorithm also reduces small motion artefacts within 3D
      reconstructions. Experiments with simulated projections from real patient data
      show the feasibility of the proposed method. In addition, experiments with real
      projection data acquired with an experimental robotised C-arm device have been
      performed with promising results.

PMID- 18051058
TI  - Cortical hemisphere registration via large deformation diffeomorphic metric curve
      mapping.
AB  - We present large deformation diffeomorphic metric curve mapping (LDDMM-Curve) for
      registering cortical hemispheres. We showed global cortical hemisphere matching
      and evaluated the mapping accuracy in five subregions of the cortex in fourteen
      MRI scans.

PMID- 18051059
TI  - Tagged volume rendering of the heart.
AB  - We present a novel system for 3-D visualisation of the heart and coronary
      arteries. Binary tags (generated offline) are combined with value-gradient
      transfer functions (specified online) allowing for interactive visualisation,
      while relaxing the offline segmentation criteria. The arteries are roughly
      segmented using a Hessian-based line filter and the pericardial cavity using a
      Fast Marching active contour. A comparison of different contour initialisations
      reveals that simple geometric shapes (such as spheres or extruded polygons)
      produce suitable results.

PMID- 18051060
TI  - One-class acoustic characterization applied to blood detection in IVUS.
AB  - Intravascular ultrasound (IVUS) is an invasive imaging modality capable of
      providing cross-sectional images of the interior of a blood vessel in real time
      and at normal video framerates (10-30 frames/s). Low contrast between the
      features of interest in the IVUS imagery remains a confounding factor in IVUS
      analysis; it would be beneficial therefore to have a method capable of detecting
      certain physical features imaged under IVUS in an automated manner. We present
      such a method and apply it to the detection of blood. While blood detection
      algorithms are not new in this field, we deviate from traditional approaches to
      IVUS signal characterization in our use of 1-class learning. This eliminates
      certain problems surrounding the need to provide "foreground" and "background"
      (or, more generally, n-class) samples to a learner. Applied to the blood
      detection problem on 40 MHz recordings made in vivo in swine, we are able to
      achieve approximately 95% sensitivity with approximately 90% specificity at a
      radial resolution of approximately 600 microm.

PMID- 18051061
TI  - Phase sensitive reconstruction for water/fat separation in MR imaging using
      inverse gradient.
AB  - This paper presents a novel method for phase unwrapping for phase sensitive
      reconstruction in MR imaging. The unwrapped phase is obtained by integrating the
      phase gradient by solving a Poisson equation. An efficient solver, which has been
      made publicly available, is used to solve the equation. The proposed method is
      demonstrated on a fat quantification MRI task that is a part of a prospective
      study of fat accumulation. The method is compared to a phase unwrapping method
      based on region growing. Results indicate that the proposed method provides more
      robust unwrapping. Unlike region growing methods, the proposed method is also
      straight-forward to implement in 3D.

PMID- 18051062
TI  - LOCUS: local cooperative unified segmentation of MRI brain scans.
AB  - We propose to carry out cooperatively both tissue and structure segmentations by
      distributing a set of local and cooperative models in a unified MRF framework.
      Tissue segmentation is performed by partitionning the volume into subvolumes
      where local MRFs are estimated in cooperation with their neighbors to ensure
      consistency. Local estimation fits precisely to the local intensity distribution
      and thus handles nonuniformity of intensity without any bias field modelization.
      Structure segmentation is performed via local MRFs that integrate localization
      constraints provided by a priori general fuzzy description of brain anatomy.
      Structure segmentation is not reduced to a postprocessing step but cooperates
      with tissue segmentation to gradually and conjointly improve models accuracy. The
      evaluation was performed using phantoms and real 3T brain scans. It shows good
      results and in particular robustness to nonuniformity and noise with a low
      computational cost.

PMID- 18051063
TI  - Spline based inhomogeneity correction for 11C-PIB PET segmentation using
      expectation maximization.
AB  - With the advent of biomarkers such as 11C-PIB and the increase in use of PET,
      automated methods are required for processing and analyzing datasets from
      research studies and in clinical settings. A common preprocessing step is the
      calculation of standardized uptake value ratio (SUVR) for inter-subject
      normalization. This requires segmented grey matter (GM) for VOI refinement.
      However 11C-PIB uptake is proportional to amyloid build up leading to
      inhomogeneities in intensities, especially within GM. Inhomogeneities present a
      challenge for clustering and pattern classification based approaches to PET
      segmentation as proposed in current literature. In this paper we modify a MR
      image segmentation technique based on expectation maximization for 11C-PIB PET
      segmentation. A priori probability maps of the tissue types are used to
      initialize and enforce anatomical constraints. We developed a Bezier spline based
      inhomogeneity correction techniques that is embedded in the segmentation
      algorithm and minimizes inhomogeneity resulting in better segmentations of 11C
      PIB PET images. We compare our inhomogeneity with a global polynomial correction
      technique and validate our approach using co-registered MRI segmentations.

PMID- 18051064
TI  - Hyperspherical von Mises-Fisher mixture (HvMF) modelling of high angular
      resolution diffusion MRI.
AB  - A mapping of unit vectors onto a 5D hypersphere is used to model and partition
      ODFs from HARDI data. This mapping has a number of useful and interesting
      properties and we make a link to interpretation of the second order spherical
      harmonic decompositions of HARDI data. The paper presents the working theory and
      experiments of using a von Mises-Fisher mixture model for directional samples.
      The MLE of the second moment of the HvMF pdf can also be related to fractional
      anisotropy. We perform error analysis of the estimation scheme in single and
      multi-fibre regions and then show how a penalised-likelihood model selection
      method can be employed to differentiate single and multiple fibre regions.

PMID- 18051065
TI  - Use of varying constraints in optimal 3-D graph search for segmentation of
      macular optical coherence tomography images.
AB  - An optimal 3-D graph search approach designed for simultaneous multiple surface
      detection is extended to allow for varying smoothness and surface interaction
      constraints instead of the traditionally used constant constraints. We apply the
      method to the intraretinal layer segmentation of 24 3-D optical coherence
      tomography (OCT) images, learning the constraints from examples in a leave-one
      subject-out fashion. Introducing the varying constraints decreased the mean
      unsigned border positioning errors (mean error of 7.3 +/- 3.7 microm using
      varying constraints compared to 8.3 +/- 4.9 microm using constant constraints and
      8.2 +/- 3.5 microm for the inter-observer variability).

PMID- 18051066
TI  - Automatic segmentation of bladder and prostate using coupled 3D deformable
      models.
AB  - In this paper, we propose a fully automatic method for the coupled 3D
      localization and segmentation of lower abdomen structures. We apply it to the
      joint segmentation of the prostate and bladder in a database of CT scans of the
      lower abdomen of male patients. A flexible approach on the bladder allows the
      process to easily adapt to high shape variation and to intensity inhomogeneities
      that would be hard to characterize (due, for example, to the level of contrast
      agent that is present). On the other hand, a statistical shape prior is enforced
      on the prostate. We also propose an adaptive non-overlapping constraint that
      arbitrates the evolution of both structures based on the availability of strong
      image data at their common boundary. The method has been tested on a database of
      16 volumetric images, and the validation process includes an assessment of inter
      expert variability in prostate delineation, with promising results.

PMID- 18051067
TI  - Characterizing spatio-temporal patterns for disease discrimination in cardiac
      echo videos.
AB  - Disease-specific understanding of echocardiographic sequences requires accurate
      characterization of spatio-temporal motion patterns. In this paper we present a
      method of automatic extraction and matching of spatio-temporal patterns from
      cardiac echo videos. Specifically, we extract cardiac regions (chambers and
      walls) using a variation of multiscale normalized cuts that combines motion
      estimates from deformable models with image intensity. We then derive spatio
      temporal trajectories of region measurements such as wall motion, volume and
      thickness. The region trajectories are then matched to infer the similarities in
      disease labels of patients. Validation results on patient data sets collected
      from many hospitals are presented.

PMID- 18051068
TI  - Integrating functional and structural images for simultaneous cardiac
      segmentation and deformation recovery.
AB  - Because of their physiological meaningfulness, cardiac physiome models have been
      used as constraints to recover patient information from medical images. Although
      the results are promising, the parameters of the physiome models are not patient
      specific, and thus affect the clinical relevance of the recovered information
      especially in pathological cases. In view of this problem, we incorporate patient
      information from body surface potential maps in the physiome model to provide a
      more patient-specific while physiological plausible guidance, which is further
      coupled with patient measurements derived from structural images to recover the
      cardiac geometry and deformation simultaneously. Experiments have been conducted
      on synthetic data to show the benefits of the framework, and on real human data
      to show its practical potential.

PMID- 18051069
TI  - Statistical shape modeling using MDL incorporating shape, appearance, and expert
      knowledge.
AB  - We propose a highly automated approach to the point correspondence problem for
      anatomical shapes in medical images. Manual landmarking is performed on a small
      subset of the shapes in the study, and a machine learning approach is used to
      elucidate the characteristic shape and appearance features at each landmark. A
      classifier trained using these features defines a cost function that drives key
      landmarks to anatomically meaningful locations after MDL-based correspondence
      establishment. Results are shown for artificial examples as well as real data.

PMID- 18051070
TI  - False positive reduction in mammographic mass detection using local binary
      patterns.
AB  - In this paper we propose a new approach for false positive reduction in the field
      of mammographic mass detection. The goal is to distinguish between the true
      recognized masses and the ones which actually are normal parenchyma. Our proposal
      is based on Local Binary Patterns (LBP) for representing salient micro-patterns
      and preserving at the same time the spatial structure of the masses. Once the
      descriptors are extracted, Support Vector Machines (SVM) are used for classifying
      the detected masses. We test our proposal using a set of 1792 suspicious regions
      of interest extracted from the DDSM database. Exhaustive experiments illustrate
      that LBP features are effective and efficient for false positive reduction even
      at different mass sizes, a critical aspect in mass detection systems. Moreover,
      we compare our proposal with current methods showing that LBP obtains better
      performance.

PMID- 18051071
TI  - Fuzzy nonparametric DTI segmentation for robust cingulum-tract extraction.
AB  - This paper presents a novel segmentation-based approach for fiber-tract
      extraction in diffusion-tensor (DT) images. Typical tractography methods,
      incorporating thresholds on fractional anisotropy and fiber curvature to
      terminate tracking, can face serious problems arising from partial voluming and
      noise. For these reasons, tractography often fails to extract thin tracts with
      sharp changes in orientation, e.g. the cingulum. Unlike tractography--which
      disregards the information in the tensors that were previously tracked--the
      proposed method extracts the cingulum by exploiting the statistical coherence of
      tensors in the entire structure. Moreover, the proposed segmentation-based method
      allows fuzzy class memberships to optimally extract information within partial
      volumed voxels. Unlike typical fuzzy-segmentation schemes employing Gaussian
      models that are biased towards ellipsoidal clusters, the proposed method models
      the manifolds underlying the classes by incorporating nonparametric data-driven
      statistical models. Furthermore, it exploits the nonparametric model to capture
      the spatial continuity and structure of the fiber bundle. The results on real DT
      images demonstrate that the proposed method extracts the cingulum bundle
      significantly more accurately as compared to tractography.

PMID- 18051073
TI  - Coronary artery segmentation and skeletonization based on competing fuzzy
      connectedness tree.
AB  - We propose a new segmentation algorithm based on competing fuzzy connectedness
      theory, which is then used for visualizing coronary arteries in 3D CT angiography
      (CTA) images. The major difference compared to other fuzzy connectedness
      algorithms is that an additional data structure, the connectedness tree, is
      constructed at the same time as the seeds propagate. In preliminary evaluations,
      accurate result have been achieved with very limited user interaction. In
      addition to improving computational speed and segmentation results, the fuzzy
      connectedness tree algorithm also includes automated extraction of the vessel
      centerlines, which is a promising approach for creating curved plane reformat
      (CPR) images along arteries' long axes.

PMID- 18051072
TI  - Adaptive metamorphs model for 3D medical image segmentation.
AB  - In this paper, we introduce an adaptive model-based segmentation framework, in
      which edge and region information are integrated and used adaptively while a
      solid model deforms toward the object boundary. Our 3D segmentation method stems
      from Metamorphs deformable models. The main novelty of our work is in that,
      instead of performing segmentation in an entire 3D volume, we propose model-based
      segmentation in an adaptively changing subvolume of interest. The subvolume is
      determined based on appearance statistics of the evolving object model, and
      within the subvolume, more accurate and object-specific edge and region
      information can be obtained. This local and adaptive scheme for computing edges
      and object region information makes our segmentation solution more efficient and
      more robust to image noise, artifacts and intensity inhomogeneity. External
      forces for model deformation are derived in a variational framework that consists
      of both edge-based and region-based energy terms, taking into account the
      adaptively changing environment. We demonstrate the performance of our method
      through extensive experiments using cardiac MR and liver CT images.

PMID- 18051074
TI  - Mixtures of Gaussians on tensor fields for DT-MRI segmentation.
AB  - In this paper, an original approach for the segmentation of tensor fields is
      proposed. Based on the modeling of the data by means of Gaussian mixtures
      directly in the tensor domain, this technique presents a wide range of
      applications in medical image processing, particularly for Diffusion Tensor
      Magnetic Resonance Imaging (DT-MRI). The performance of the segmentation method
      proposed is shown through the segmentation of the corpus callosum from a dataset
      of 32 DT-MRI volumes. Comparison with a recent and related segmentation approach
      is favorable to our method, showing its capability for the automatic extraction
      of anatomical structures in the white matter.

PMID- 18051075
TI  - Soft level set coupling for LV segmentation in gated perfusion SPECT.
AB  - We present a new segmentation approach for the myocardium in gated and non-gated
      perfusion SPECT images. To this end, we represent the epi- and endocardium by
      separate signed distance functions and couple them by a soft constraint to give
      explicit control over the wall thickness. By an explicit modeling of the basal
      plane, the volume of the blood pool as well as the myocardium are determinable.
      Furthermore, prior shape information is incorporated by applying a kernel density
      estimation on a number of expert segmentations in a low-dimensional PCA subspace.
      Thereby, information along the time axis is fully taken into account by employing
      4-dimensional embedding functions.

PMID- 18051076
TI  - Nonrigid image registration with subdivision lattices: application to cardiac MR
      image analysis.
AB  - In this paper we present a new methodology for cardiac motion tracking in tagged
      MRI using nonrigid image registration based on subdivision surfaces and
      subdivision lattices. We use two sets of registrations to do the motion tracking.
      First, a set of surface registrations is used to create and initially align the
      subdivision model of the left ventricle with short-axis and long-axis MR images.
      Second, a series of volumetric registrations are used to perform the motion
      tracking and to reconstruct the 4D cardiac motion field from the tagged MR
      images. The motion of a point in the myocardium over time is calculated by
      registering the images taken during systole to the set of reference images taken
      at end-diastole. Registration is achieved by optimizing the positions of the
      vertices in the base lattice so that the mutual information of the images being
      registered is maximized. The presented method is validated using a cardiac motion
      simulator and we also present strain measurements obtained from a group of normal
      volunteers.

PMID- 18051077
TI  - Spatio-temporal registration of real time 3D ultrasound to cardiovascular MR
      sequences.
AB  - We extend our static multimodal nonrigid registration to a spatio-temporal (2D+T)
      co-registration of a real-time 3D ultrasound and a cardiovascular MR sequence.
      The motivation for our research is to assist a clinician to automatically fuse
      the information from multiple imaging modalities for the early diagnosis and
      therapy of cardiac disease. The deformation field between both sequences is
      decoupled into spatial and temporal components. Temporal alignment is firstly
      performed to re-slice both sequences using a differential registration method.
      Spatial alignment is then carried out between the frames corresponding to the
      same temporal position. The spatial deformation is modeled by the polyaffine
      transformation whose anchor points (or control points) are automatically detected
      and refined by calculating a local mis-match measure based on phase mutual
      information. The spatial alignment is built in an adaptive multi-scale framework
      to maximize the phase-based similarity measure by optimizing the parameters of
      the polyaffine transformation. Results demonstrate that this novel method can
      yield an accurate registration to particular cardiac regions.

PMID- 18051078
TI  - Nonlinear registration of diffusion MR images based on fiber bundles.
AB  - In this paper, we explore the use of fiber bundles extracted from diffusion MR
      images for a nonlinear registration algorithm. We employ a white matter atlas to
      automatically label major fiber bundles and to establish correspondence between
      subjects. We propose a polyaffine framework to calculate a smooth and invertible
      nonlinear warp field based on these correspondences, and derive an analytical
      solution for the reorientation of the tensor fields under the polyaffine
      transformation. We demonstrate our algorithm on a group of subjects and show that
      it performs comparable to a higher dimensional nonrigid registration algorithm.

PMID- 18051079
TI  - Multivariate normalization with symmetric diffeomorphisms for multivariate
      studies.
AB  - Current clinical and research neuroimaging protocols acquire images using
      multiple modalities, for instance, T1, T2, diffusion tensor and cerebral blood
      flow magnetic resonance images (MRI). These multivariate datasets provide unique
      and often complementary anatomical and physiological information about the
      subject of interest. We present a method that uses fused multiple modality
      (scalar and tensor) datasets to perform intersubject spatial normalization. Our
      multivariate approach has the potential to eliminate inconsistencies that occur
      when normalization is performed on each modality separately. Furthermore, the
      multivariate approach uses a much richer anatomical and physiological image
      signature to infer image correspondences and perform multivariate statistical
      tests. In this initial study, we develop the theory for Multivariate Symmetric
      Normalization (MVSyN), establish its feasibility and discuss preliminary results
      on a multivariate statistical study of 22q deletion syndrome.

PMID- 18051080
TI  - Non-rigid surface registration using spherical thin-plate splines.
AB  - Accurate registration of cortical structures plays a fundamental role in
      statistical analysis of brain images across population. This paper presents a
      novel framework for the non-rigid intersubject brain surface registration, using
      conformal structure and spherical thin-plate splines. By resorting to the
      conformal structure, complete characteristics regarding the intrinsic cortical
      geometry can be retained as a mean curvature function and a conformal factor
      function defined on a canonical, spherical domain. In this transformed space,
      spherical thin-plate splines are firstly used to explicitly match a few prominent
      homologous landmarks, and in the meanwhile, interpolate a global deformation
      field. A post-optimization procedure is then employed to further refine the
      alignment of minor cortical features based on the geometric parameters preserved
      on the domain. Our experiments demonstrate that the proposed framework is highly
      competitive with others for brain surface registration and population-based
      statistical analysis. We have applied our method in the identification of
      cortical abnormalities in PET imaging of patients with neurological disorders and
      accurate results are obtained.

PMID- 18051081
TI  - A study of hippocampal shape difference between genders by efficient hypothesis
      test and discriminative deformation.
AB  - Hypothesis testing is an important way to detect the statistical difference
      between two populations. In this paper, we use the Fisher permutation and
      bootstrap tests to differentiate hippocampal shape between genders. These methods
      are preferred to traditional hypothesis tests which impose assumptions on the
      distribution of the samples. An efficient algorithm is adopted to rapidly perform
      the exact tests. We extend this algorithm to multivariate data by projecting the
      original data onto an "informative direction" to generate a scalar test
      statistic. This "informative direction" is found to preserve the original
      discriminative information. This direction is further used in this paper to
      isolate the discriminative shape difference between classes from the individual
      variability, achieving a visualization of shape discrepancy.

PMID- 18051082
TI  - Graph cuts framework for kidney segmentation with prior shape constraints.
AB  - We propose a novel kidney segmentation approach based on the graph cuts
      technique. The proposed approach depends on both image appearance and shape
      information. Shape information is gathered from a set of training shapes. Then we
      estimate the shape variations using a new distance probabilistic model which
      approximates the marginal densities of the kidney and its background in the
      variability region using a Poisson distribution refined by positive and negative
      Gaussian components. To segment a kidney slice, we align it with the training
      slices so we can use the distance probabilistic model. Then its gray level is
      approximated with a LCG with sign-alternate components. The spatial interaction
      between the neighboring pixels is identified using a new analytical approach.
      Finally, we formulate a new energy function using both image appearance models
      and shape constraints. This function is globally minimized using s/t graph cuts
      to get the optimal segmentation. Experimental results show that the proposed
      technique gives promising results compared to others without shape constraints.

PMID- 18051084
TI  - Real-time synthesis of image slices in deformed tissue from nominal volume
      images.
AB  - This paper presents a fast image synthesis procedure for elastic volumes under
      deformation. Given the node displacements of a mesh and the 3D image voxel data
      of an undeformed volume, the method maps the image plane pixels to be synthesized
      from the deformed configuration back to the nominal pre-deformed configuration,
      where the pixel intensities are obtained easily through interpolation in the
      regular-grid structure of the voxel volume. For smooth interpolation, this
      mapping requires the identification of the mesh element enclosing each image
      pixel. To accelerate this point location procedure, a fast method of marking the
      image pixels is employed by finding the intersection of the mesh and the image,
      and marking this intersection on the image pixels using Bresenham's line drawing
      algorithm. A deformable tissue phantom was constructed, it was modeled using the
      finite element method, and its 3D ultrasound volume was acquired in its
      undeformed state. Actual B-mode images of the phantom under deformation by the
      ultrasound probe were then compared with the corresponding synthesized images
      simulated for the same deformations. Results show that realistic images can be
      synthesized in real-time using the proposed technique.

PMID- 18051083
TI  - Attenuation resilient AIF estimation based on hierarchical Bayesian modelling for
      first pass myocardial perfusion MRI.
AB  - Non-linear attenuation of the Arterial Input Function (AIF) is a major problem in
      first-pass MR perfusion imaging due to the high concentration of the contrast
      agent in the blood pool. This paper presents a technique to reconstruct the true
      AIF using signal intensities in the myocardium and the attenuated AIF based on a
      Hierarchical Bayesian Model (HBM). With the proposed method, both the AIF and the
      response function are modeled as smoothed functions by using Bayesian penalty
      splines (P-Splines). The derived AIF is then used to estimate the impulse
      response of the myocardium based on deconvolution analysis. The proposed
      technique is validated both with simulated data using the MMID4 model and ten in
      vivo data sets for estimating myocardial perfusion reserve rates. The results
      demonstrate the ability of the proposed technique in accurately reconstructing
      the desired AIF for myocardial perfusion quantification. The method does not
      involve any MRI pulse sequence modification, and thus is expected to have wider
      clinical impact.

PMID- 18051085
TI  - Quantitative comparison of two cortical surface extraction methods using MRI
      phantoms.
AB  - In the last decade several methods for extracting the human cerebral cortex from
      magnetic resonance images have been proposed. Studies comparing these methods
      have been few. In this study we compare a recent cortical extraction method with
      FreeSurfer, which has been widespread in the scientific community during recent
      years. The comparison is performed using realistic phantoms generated from
      surfaces extracted from original brain scans. The geometrical accuracy of the
      reconstructed surfaces is compared to the surfaces extracted from the original
      scan. We found that our method is comparable with FreeSurfer in terms of
      accuracy, and in some cases it performs better. In terms of speed our method is
      more than 25 times faster.

PMID- 18051086
TI  - Stabilization of image motion for robotic assisted beating heart surgery.
AB  - The performance of robotic assisted minimally invasive beating heart surgery is a
      challenging task due to the rhythmic motion of the heart, which hampers delicate
      tasks such as small vessel anastomosis. In this paper, a virtual motion
      compensation scheme is proposed for stabilizing images from the surgical site.
      The method uses vision based 3D tracking to accurately infer cardiac surface
      deformation and augmented reality for rendering a motion stabilized view for
      improved surgical performance. The method forgoes the need of fiducial markers
      and can be integrated with the existing master-slave robotic consoles. The
      proposed technique is validated with both simulated surgical scenes with known
      ground truth and in vivo data acquired from a TECAB procedure. The experimental
      results demonstrate the potential of the proposed technique in performing
      microscale tasks in a moving frame of reference with improved precision and
      repeatability.

PMID- 18051087
TI  - Robotic assistant for transperineal prostate interventions in 3T closed MRI.
AB  - Numerous studies have demonstrated the efficacy of image-guided needle-based
      therapy and biopsy in the management of prostate cancer. The accuracy of
      traditional prostate interventions performed using transrectal ultrasound (TRUS)
      is limited by image fidelity, needle template guides, needle deflection and
      tissue deformation. Magnetic Resonance Imaging (MRI) is an ideal modality for
      guiding and monitoring such interventions due to its excellent visualization of
      the prostate, its sub-structure and surrounding tissues. We have designed a
      comprehensive robotic assistant system that allows prostate biopsy and
      brachytherapy procedures to be performed entirely inside a 3T closed MRI scanner.
      We present a detailed design of the robotic manipulator and an evaluation of its
      usability and MR compatibility.

PMID- 18051088
TI  - Virtually extended surgical drilling device: virtual mirror for navigated spine
      surgery.
AB  - This paper introduces a new method for navigated spine surgery using a
      stereoscopic video see-through head-mounted display (HMD) and an optical tracking
      system. Vertebrae are segmented from volumetric CT data and visualized in-situ. A
      surgical drilling device is virtually extended with a mirror for intuitive
      planning of the drill canal, control of drill direction and insertion depth. The
      first designated application for the virtually extended drilling device is the
      preparation of canals for pedicle screw implantation in spine surgery. The
      objective of surgery is to install an internal fixateur for stabilization of
      injured vertebrae. We invited five surgeons of our partner clinic to test the
      system with realistic replica of lumbar vertebrae and compared the new approach
      with the classical, monitor-based navigation system providing three orthogonal
      slice views on the operation site. We measured time of procedure and scanned the
      drilled vertebrae with CT to verify accuracy of drilling.

PMID- 18051089
TI  - Improved statistical TRE model when using a reference frame.
AB  - Target registration error (TRE) refers to the uncertainty in localizing a point
      of interest after a point-based registration is performed. Common in medical
      image registration, the metric is typically represented as a root-mean-square
      statistic. In the late 1990s, a statistical model was developed based on the
      rigid body definition of the fiducial markers and the localization error
      associated in measuring the fiducials. The statistical model assumed that the
      fiducial localizer error was isotropic, but recently the model was reworked to
      handle anisotropic fiducial localizer error (FLE). In image guided surgery, the
      statistical model is used to predict the surgical tool tip tracking accuracy
      associated with optical spatial measurement systems for which anisotropic FLE
      models are required. However, optical tracking systems often track the surgical
      tools relative to a patient based reference tool. Here the formulation for
      modeling the TRE of a surgical probe relative to a reference frame is developed
      mathematically and evaluated using a Monte Carlo simulation. The effectiveness of
      the statistical model is directly related to the FLE model, the fiducial marker
      design and the distance from centroid to target.

PMID- 18051090
TI  - 3D/2D image registration: the impact of X-ray views and their number.
AB  - An important part of image-guided radiation therapy or surgery is registration of
      a three-dimensional (3D) preoperative image to two-dimensional (2D) images of the
      patient. It is expected that the accuracy and robustness of a 3D/2D image
      registration method do not depend solely on the registration method itself but
      also on the number and projections (views) of intraoperative images. In this
      study, we systematically investigate these factors by using registered image
      data, comprising of CT and X-ray images of a cadaveric lumbar spine phantom and
      the recently proposed 3D/2D registration method. The results indicate that the
      proportion of successful registrations (robustness) significantly increases when
      more X-ray images are used for registration.

PMID- 18051091
TI  - Magneto-optic tracking of a flexible laparoscopic ultrasound transducer for
      laparoscope augmentation.
AB  - In abdominal surgery, a laparoscopic ultrasound transducer is commonly used to
      detect lesions such as metastases. The determination and visualization of
      position and orientation of its flexible tip in relation to the patient or other
      surgical instruments can be of much help to (novice) surgeons utilizing the
      transducer intraoperatively. This difficult subject has recently been paid
      attention to by the scientific community . Electromagnetic tracking systems can
      be applied to track the flexible tip. However, the magnetic field can be
      distorted by ferromagnetic material. This paper presents a new method based on
      optical tracking of the laparoscope and magneto-optic tracking of the transducer,
      which is able to automatically detect field distortions. This is used for a
      smooth augmentation of the B-scan images of the transducer directly on the camera
      images in real time.

PMID- 18051092
TI  - Evaluation of a novel calibration technique for optically tracked oblique
      laparoscopes.
AB  - This paper proposes an evaluation of a novel calibration method for an optically
      tracked oblique laparoscope. We present the necessary tools to track an oblique
      scope and a camera model which includes changes to the intrinsic camera
      parameters thereby extending previously proposed methods. Because oblique scopes
      offer a wide 'virtual' view on the surgical field, the method is of great
      interest for augmented reality guidance of laparoscopic interventions using an
      oblique scope. The model and an approximated version are evaluated in an
      extensive validation study. Using 5 sets of 40 calibration images, we compare
      both camera models (i.e. model and approximation) and 2 interpolation schemes.
      The selected model and interpolation scheme reaches an average accuracy of 2.60
      pixel and an equivalent 3D error of 0.60 mm. Finally, we present initial
      experience of the presented approach with an oblique scope and optical tracking
      in a clinical setup. During a laparoscopic rectum resection surgery the setup was
      used to augment the scene with a model of the pelvis. The method worked properly
      and the attached probes did not interfere with normal procedure.

PMID- 18051093
TI  - Fiducial-free registration procedure for navigated bronchoscopy.
AB  - Navigated bronchoscopy has been developed by various groups within the last
      decades. Systems based on CT data and electromagnetic tracking enable the
      visualization of the position and orientation of the bronchoscope, forceps, and
      biopsy tools within CT data. Therefore registration between the tracking space
      and the CT volume is required. Standard procedures are based on point-based
      registration methods that require selecting corresponding natural landmarks in
      both coordinate systems by the examiner. We developed a novel algorithm for a
      fully automatic registration procedure in navigated bronchoscopy based on the
      trajectory recorded during routine examination of the airways at the beginning of
      an intervention. The proposed system provides advantages in terms of an unchanged
      medical workflow and high accuracy. We compared the novel method with point-based
      and ICP-based registration. Experiments demonstrate that the novel method
      transforms up to 97% of tracking points inside the segmented airways, which was
      the best performance compared to the other methods.

PMID- 18051094
TI  - Automatic target and trajectory identification for deep brain stimulation (DBS)
      procedures.
AB  - This paper presents an automatic surgical target and trajectory identification
      technique for planning deep brain stimulation (DBS) procedures. The probabilistic
      functional maps, constructed from population-based actual stimulating field
      information and intra-operative electrophysiological activities, were integrated
      into a neurosurgical visualization and navigation system to facilitate the
      surgical planning and guidance. In our preliminary studies, we compared the
      actual surgical target locations and trajectories established by an experienced
      stereotactic neurosurgeon with those automatically planned using our
      probabilistic functional maps on 10 subthalamic nucleus (STN) DBS procedures. The
      average displacement between the surgical target locations in both groups was
      1.82mm with a standard deviation of 0.77mm. The difference between the surgical
      trajectories was 3.1 degrees and 2.3 degrees in the lateral-to-medial and
      anterior-to-posterior orientations respectively.

PMID- 18051095
TI  - Application of open source image guided therapy software in MR-guided therapies.
AB  - We present software engineering methods to provide free open-source software for
      MR-guided therapy. We report that graphical representation of the surgical tools,
      interconnectively with the tracking device, patient-to-image registration, and
      MRI-based thermal mapping are crucial components of MR-guided therapy in sharing
      such software. Software process includes a network-based distribution mechanism
      by multi-platform compiling tool CMake, CVS, quality assurance software DART. We
      developed six procedures in four separate clinical sites using proposed software
      engineering and process, and found the proposed method is feasible to facilitate
      multicenter clinical trial of MR-guided therapies. Our future studies include use
      of the software in non-MR-guided therapies.

PMID- 18051096
TI  - Statistical atlases of bone anatomy: construction, iterative improvement and
      validation.
AB  - We present an iterative bootstrapping framework to create and analyze statistical
      atlases of bony anatomy such as the human pelvis from a large collection of CT
      data sets. We create an initial tetrahedral mesh representation of the target
      anatomy and use deformable intensity-based registration to create an initial
      atlas. This atlas is used as prior information to assist in deformable
      registration/segmentation of our subject image data sets, and the process is
      iterated several times to remove any bias from the initial choice of template
      subject and to improve the stability and consistency of mean shape and
      variational modes. We also present a framework to validate the statistical
      models. Using this method, we have created a statistical atlas of full pelvis
      anatomy with 110 healthy patient CT scans. Our analysis shows that any given
      pelvis shape can be approximated up to an average accuracy of 1.5036 mm using the
      first 15 principal modes of variation. Although a particular intensity-based
      deformable registration algorithm was used to produce these results, we believe
      that the basic method may be adapted readily for use with any registration method
      with broadly similar characteristics.

PMID- 18051097
TI  - A new benchmark for shape correspondence evaluation.
AB  - This paper introduces a new benchmark study of evaluating landmark-based shape
      correspondence used for statistical shape analysis. Different from previous shape
      correspondence evaluation methods, the proposed benchmark first generates a large
      set of synthetic shape instances by randomly sampling a specified ground-truth
      statistical shape model. We then run the test shape-correspondence algorithms on
      these synthetic shape instances to construct a new statistical shape model. We
      finally introduce a new measure to describe the difference between this newly
      constructed statistical shape model and the ground truth. This new measure is
      then used to evaluate the performance of the test shape-correspondence algorithm.
      By introducing the ground-truth statistical shape model, we believe the proposed
      benchmark allows for a more objective evaluation of the shape correspondence than
      those that do not specify any ground truth.

PMID- 18051098
TI  - Automatic inference of sulcus patterns using 3D moment invariants.
AB  - The goal of this work is the automatic inference of frequent patterns of the
      cortical sulci, namely patterns that can be observed only for a subset of the
      population. The sulci are detected and identified using brainVISA open software.
      Then, each sulcus is represented by a set of shape descriptors called the 3D
      moment invariants. Unsupervised agglomerative clustering is performed to define
      the patterns. A ratio between compactness and contrast among clusters is used to
      select the best patterns. A pattern is considered significant when this ratio is
      statistically better than the ratios obtained for clouds of points following a
      Gaussian distribution. The patterns inferred for the left cingulate sulcus are
      consistent with the patterns described in the atlas of Ono.

PMID- 18051099
TI  - Classifier selection strategies for label fusion using large atlas databases.
AB  - Structural segmentations of brain MRI can be generated by propagating manually
      labelled atlas images from a repository to a query subject and combining them.
      This method has been shown to be robust, consistent and increasingly accurate
      with increasing numbers of classifiers. It outperforms standard atlas-based
      segmentation but suffers, however, from problems of scale when the number of
      atlases is large. For a large repository and a particular query subject, using a
      selection strategy to identify good classifiers is one way to address problems of
      scale. This work presents and compares different classifier selection strategies
      which are applied to a group of 275 subjects with manually labelled brain MR
      images. We approximate an upper limit for the accuracy or overlap that can be
      achieved for a particular structure in a given subject and compare this with the
      accuracy obtained using classifier selection. The accuracy of different
      classifier selection strategies are also rated against the distribution of
      overlaps generated by random groups of classifiers.

PMID- 18051100
TI  - Groupwise combined segmentation and registration for atlas construction.
AB  - The creation of average anatomical atlases has been a growing area of research in
      recent years. It is of increased value to construct representations of, not only
      intensity atlases, but also their segmentation into required tissues or
      structures. This paper presents novel groupwise combined segmentation and
      registration approaches, which aim to simultaneously improve both the alignment
      of intensity images to their average shape, as well as the segmentations of
      structures in the average space. An iterative EM framework is used to build
      average 3D MR atlases of populations for which prior atlases do not currently
      exist: preterm infants at one- and two-years old. These have been used to
      quantify the growth of tissues occurring between these ages.

PMID- 18051101
TI  - Subject-specific biomechanical simulation of brain indentation using a meshless
      method.
AB  - We develop a meshless method for simulating soft organ deformation. The method is
      motivated by simple, automatic model creation for real-time simulation. Our
      method is meshless in the sense that deformation is calculated at nodes that are
      not part of an element mesh. Node placement is almost arbitrary. Fully
      geometrically nonlinear total Lagrangian formulation is used. Geometric
      integration is performed over a regular background grid that does not conform to
      the simulation geometry. Explicit time integration is used via the central
      difference method. To validate the method we simulate indentation of a swine
      brain and compare the results to experimental data.

PMID- 18051102
TI  - Towards an identification of tumor growth parameters from time series of images.
AB  - In cancer treatment, understanding the aggressiveness of the tumor is essential
      in therapy planning and patient follow-up. In this article, we present a novel
      method for quantifying the speed of invasion of gliomas in white and grey matter
      from time series of magnetic resonance (MR) images. The proposed approach is
      based on mathematical tumor growth models using the reaction-diffusion formalism.
      The quantification process is formulated by an inverse problem and solved using
      anisotropic fast marching method yielding an efficient algorithm. It is tested on
      a few images to get a first proof of concept with promising new results.

PMID- 18051103
TI  - Real-time modeling of vascular flow for angiography simulation.
AB  - Interventional neuroradiology is a growing field of minimally invasive therapies
      that includes embolization of aneurysms and arteriovenous malformations, carotid
      angioplasty and carotid stenting, and acute stroke therapy. Treatment is
      performed using image-guided instrument navigation through the patient's
      vasculature and requires intricate combination of visual and tactile
      coordination. In this paper we present a series of techniques for real-time high
      fidelity simulation of angiographic studies. We focus in particular on the
      computation and visualization of blood flow and blood pressure distribution
      patterns, mixing of blood and contrast agent, and high-fidelity simulation of
      fluoroscopic images.

PMID- 18051104
TI  - A training system for ultrasound-guided needle insertion procedures.
AB  - Needle placement into a patient body under guidance of ultrasound is a frequently
      performed procedure in clinical practice. Safe and successful performance of such
      procedure requires a high level of spatial reasoning and hand-eye co-ordination
      skills, which must be developed through intensive practice. In this paper we
      present a training system designed to improve the skills of interventional
      radiology trainees in ultrasound-guided needle placement procedures. Key issues
      involved in the system include surface and volumetric registration, solid texture
      modelling, spatial calibration, and real-time synthesis and rendering of
      ultrasound images. Moreover, soft tissue deformation caused by the needle
      movement and needle cutting is realised using a mass-spring-model approach. These
      have led to a realistic ultrasound simulation system, which has been shown to be
      a useful tool for the training of needle insertion procedures. Preliminary
      results of a construct evaluation study indicate the effectiveness and usefulness
      of the developed training system.

PMID- 18051105
TI  - Anisotropic wave propagation and apparent conductivity estimation in a fast
      electrophysiological model: application to XMR interventional imaging.
AB  - Cardiac arrhythmias are increasingly being treated using ablation procedures.
      Development of fast electrophysiological models and estimation of parameters
      related to conduction pathologies can aid in the investigation of better
      treatment strategies during Radio-frequency ablations. We present a fast
      electrophysiological model incorporating anisotropy of the cardiac tissue. A
      global-local estimation procedure is also outlined to estimate a hidden parameter
      (apparent electrical conductivity) present in the model. The proposed model is
      tested on synthetic and real data derived using XMR imaging. We demonstrate a
      qualitative match between the estimated conductivity parameter and possible
      pathology locations. This approach opens up possibilities to directly integrate
      modelling in the intervention room.

PMID- 18051106
TI  - Automatic trajectory planning for deep brain stimulation: a feasibility study.
AB  - DBS for Parkinson's disease involves an extensive planning to find a suitable
      electrode implantation path to the selected target. We have investigated the
      feasibility of improving the conventional planning with an automatic calculation
      of possible paths in 3D. This requires the segmentation of anatomical structures.
      Subsequently, the paths are calculated and visualized. After selection of a
      suitable path, the settings for the stereotactic frame are determined. A
      qualitative evaluation has shown that automatic avoidance of critical structures
      is feasible. The participating neurosurgeons estimate the time gain to be around
      30 minutes.

PMID- 18051107
TI  - Automatic segmentation of blood vessels from dynamic MRI datasets.
AB  - In this paper we present an approach for blood vessel segmentation from dynamic
      contrast-enhanced MRI datasets of the hand joints acquired from patients with
      active rheumatoid arthritis. Exclusion of the blood vessels is needed for
      accurate visualisation of the activation events and objective evaluation of the
      degree of inflammation. The segmentation technique is based on statistical
      modelling motivated by the physiological properties of the individual tissues,
      such as speed of uptake and concentration of the contrast agent; it incorporates
      Markov random field probabilistic framework and principal component analysis. The
      algorithm was tested on 60 temporal slices and has shown promising results.

PMID- 18051108
TI  - Automated planning of scan geometries in spine MRI scans.
AB  - Consistency of MR scan planning is very important for diagnosis, especially in
      multi-site trials and follow-up studies, where disease progress or response to
      treatment is evaluated. Accurate manual scan planning is tedious and requires
      skillful operators. On the other hand, automated scan planning is difficult due
      to relatively low quality of survey images ("scouts") and strict processing time
      constraints. This paper presents a novel method for automated planning of MRI
      scans of the spine. Lumbar and cervical examinations are considered, although the
      proposed method is extendible to other types of spine examinations, such as
      thoracic or total spine imaging. The automated scan planning (ASP) system
      consists of an anatomy recognition part, which is able to automatically detect
      and label the spine anatomy in the scout scan, and a planning part, which
      performs scan geometry planning based on recognized anatomical landmarks. A
      validation study demonstrates the robustness of the proposed method and its
      feasibility for clinical use.

PMID- 18051109
TI  - Cardiac-motion compensated MR imaging and strain analysis of ventricular
      trabeculae.
AB  - In conventional CMR, bulk cardiac motion causes target structures to move in and
      out of the static acquisition plane. Due to the partial volume effect, accurate
      localisation of subtle features through the cardiac cycle, such as the trabeculae
      and papillary muscles, is difficult. This problem is exacerbated by the short
      acquisition window necessary to avoid motion blur and ghosting, especially during
      early systole. This paper presents an adaptive imaging approach with COMB multi
      tag tracking that follows true 3D motion of the myocardium so that the same
      tissue slice is imaged throughout the cine acquisition. The technique is
      demonstrated with motion-compensated multi-slice imaging of ventricles, which
      allows for tracked visualisation and analysis of the trabeculae and papillary
      muscles for the first time. This enables novel in-vivo measurement of
      circumferential and radial strain for trabeculation and papillary muscle
      contractility. These statistics will facilitate the evaluation of diseases such
      as mitral valve insufficiency and ischemic heart disease. The adaptive imaging
      technique will also have significant implications for CMR in general, including
      motion-compensated quantification of myocardial perfusion and blood flow, and
      motion-correction of sequences with long acquisition windows.

PMID- 18051110
TI  - High throughput analysis of breast cancer specimens on the grid.
AB  - Breast cancer accounts for about 30% of all cancers and 15% of all cancer deaths
      in women in the United States. Advances in computer assisted diagnosis (CAD)
      holds promise for early detecting and staging disease progression. In this paper
      we introduce a Grid-enabled CAD to perform automatic analysis of imaged
      histopathology breast tissue specimens. More than 100,000 digitized samples (1200
      x 1200 pixels) have already been processed on the Grid. We have analyzed results
      for 3744 breast tissue samples, which were originated from four different
      institutions using diaminobenzidine (DAB) and hematoxylin staining. Both linear
      and nonlinear dimension reduction techniques are compared, and the best one
      (ISOMAP) was applied to reduce the dimensionality of the features. The
      experimental results show that the Gentle Boosting using an eight node CART
      decision tree as the weak learner provides the best result for classification.
      The algorithm has an accuracy of 86.02% using only 20% of the specimens as the
      training set.

PMID- 18051111
TI  - Thoracic CT-PET registration using a 3D breathing model.
AB  - In the context of thoracic CT-PET volume registration, we present a novel method
      to incorporate a breathing model in a non-linear registration procedure,
      guaranteeing physiologically plausible deformations. The approach also accounts
      for the rigid motions of lung tumors during breathing. We performed a set of
      registration experiments on one healthy and four pathological data sets. Initial
      results demonstrate the interest of this method to significantly improve the
      accuracy of multimodal volume registration for diagnosis and radiotherapy
      applications.

PMID- 18051112
TI  - Quantification of blood flow from rotational angiography.
AB  - For assessment of cerebrovascular diseases, it is beneficial to obtain three
      dimensional (3D) information on vessel morphology and hemodynamics. Rotational
      angiography is routinely used to determine the 3D geometry and we propose a
      method to exploit the same acquisition to determine the blood flow waveform and
      the mean volumetric flow rate. The method uses a model of contrast agent
      dispersion to determine the flow parameters from the spatial and temporal
      development of the contrast agent concentration, represented by a flow map.
      Furthermore, it also overcomes artifacts due to the rotation of the c-arm using a
      newly introduced reliability map. The method was validated on images from a
      computer simulation and from a phantom experiment. With a mean error of 11.0% for
      the mean volumetric flow rate and 15.3% for the blood flow waveform from the
      phantom experiments, we conclude that the method has the potential to give
      quantitative estimates of blood flow parameters during cerebrovascular
      interventions.

PMID- 18051113
TI  - Modeling glioma growth and mass effect in 3D MR images of the brain.
AB  - In this article, we propose a framework for modeling glioma growth and the
      subsequent mechanical impact on the surrounding brain tissue (mass-effect) in a
      medical imaging context. Glioma growth is modeled via nonlinear reaction
      advection-diffusion, with a two-way coupling with the underlying tissue elastic
      deformation. Tumor bulk and infiltration and subsequent mass-effects are not
      regarded separately, but captured by the model itself in the course of its
      evolution. Our formulation is fully Eulerian and naturally allows for updating
      the tumor diffusion coefficient following structural displacements caused by
      tumor growth/infiltration. We show that model parameters can be estimated via
      optimization based on imaging data, using efficient solution algorithms on
      regular grids. We test the model and the automatic optimization framework on real
      brain tumor data sets, achieving significant improvement in landmark prediction
      compared to a simplified purely mechanical approach.

PMID- 18051114
TI  - Towards tracking breast cancer across medical images using subject-specific
      biomechanical models.
AB  - Breast cancer detection, diagnosis and treatment increasingly involves images of
      the breast taken with different degrees of breast deformation. We introduce a new
      biomechanical modelling framework for predicting breast deformation and thus
      aiding the combination of information derived from the various images. In this
      paper, we focus on MR images of the breast under different loading conditions,
      and consider methods to map information between the images. We generate subject
      specific finite element models of the breast by semi-automatically fitting
      geometrical models to segmented data from breast MR images, and characterizing
      the subject-specific mechanical properties of the breast tissues. We identified
      the unloaded reference configuration of the breast by acquiring MR images of the
      breast under neutral buoyancy (immersed in water). Such imaging is clearly not
      practical in the clinical setting, however this previously unavailable data
      provides us with important data with which to validate models of breast
      biomechanics, and provides a common configuration with which to refer and
      interpret all breast images. We demonstrate our modelling framework using a pilot
      study that was conducted to assess the mechanical performance of a subject
      specific homogeneous biomechanical model in predicting deformations of the breast
      of a volunteer in a prone gravity-loaded configuration. The model captured the
      gross characteristics of the breast deformation with an RMS error of 4.2 mm in
      predicting the skin surface of the gravity-loaded shape, which included tissue
      displacements of over 20 mm. Internal tissue features identified from the MR
      images were tracked from the reference state to the prone gravity-loaded
      configuration with a mean error of 3.7 mm. We consider the modelling assumptions
      and discuss how the framework could be refined in order to further improve the
      tissue tracking accuracy.

PMID- 18051115
TI  - Inter-subject modelling of liver deformation during radiation therapy.
AB  - This paper presents a statistical model of the liver deformation that occurs in
      addition to the quasi-periodic respiratory motion. Having an elastic but still
      compact model of this variability is an important step towards reliable targeting
      in radiation therapy. To build this model, the deformation of the liver at
      exhalation was determined for 12 volunteers over roughly one hour using 4DMRI and
      subsequent non-rigid registration. The correspondence between subjects was
      established based on mechanically relevant landmarks on the liver surface. Leave
      one-out experiments were performed to evaluate the accuracy in predicting the
      liver deformation from partial information, such as a point tracked by ultrasound
      imaging. Already predictions from a single point strongly reduced the
      localisation errors, whilst the method is robust with respect to the exact choice
      of the measured predictor.

PMID- 18051116
TI  - Contributions to 3D diffeomorphic atlas estimation: application to brain images.
AB  - This paper focuses on the estimation of statistical atlases of 3D images by means
      of diffeomorphic transformations. Within a Log-Euclidean framework, the
      exponential and logarithm maps of diffeomorphisms need to be computed. In this
      framework, the Inverse Scaling and Squaring (ISS) method has been recently
      extended for the computation of the logarithm map, which is one of the most time
      demanding stages. In this work we propose to apply the Baker-Campbell-Hausdorff
      (BCH) formula instead. In a 3D simulation study, BCH formula and ISS method
      obtained similar accuracy but BCH formula was more than 100 times faster. This
      approach allowed us to estimate a 3D statistical brain atlas in a reasonable
      time, including the average and the modes of variation. Details for the
      computation of the modes of variation in the Sobolev tangent space of
      diffeomorphisms are also provided.

PMID- 18051117
TI  - Measuring brain variability via sulcal lines registration: a diffeomorphic
      approach.
AB  - In this paper we present a new way of measuring brain variability based on the
      registration of sulcal lines sets in the large deformation framework. Lines are
      modelled geometrically as currents, avoiding then matchings based on point
      correspondences. At the end we retrieve a globally consistent deformation of the
      underlying brain space that best matches the lines. Thanks to this framework the
      measured variability is defined everywhere whereas a previous method introduced
      by P. Fillard requires tensors extrapolation. Evaluating both methods on the same
      database, we show that our new approach enables to describe different details of
      the variability and to highlight the major trends of deformation in the database
      thanks to a Tangent-PCA analysis.

PMID- 18051118
TI  - Effects of registration regularization and atlas sharpness on segmentation
      accuracy.
AB  - In this paper, we propose a unified framework for computing atlases from manually
      labeled data at various degrees of "sharpness" and the joint registration
      segmentation of a new brain with these atlases. In non-rigid registration, the
      tradeoff between warp regularization and image fidelity is typically set
      empirically. In segmentation, this leads to a probabilistic atlas of arbitrary
      "sharpness": weak regularization results in well-aligned training images and a
      "sharp" atlas; strong regularization yields a "blurry" atlas. We study the
      effects of this tradeoff in the context of cortical surface parcellation by
      comparing three special cases of our framework, namely: progressive registration
      segmentation of a new brain to increasingly "sharp" atlases with increasingly
      flexible warps; secondly, progressive registration to a single atlas with
      increasingly flexible warps; and thirdly, registration to a single atlas with
      fixed constrained warps. The optimal parcellation in all three cases corresponds
      to a unique balance of atlas "sharpness" and warp regularization that yield
      statistically significant improvements over the previously demonstrated
      parcellation results.

PMID- 18051119
TI  - Generalized surface flows for deformable registration and cortical matching.
AB  - Despite being routinely required in medical applications, deformable surface
      registration is notoriously difficult due to large intersubject variability and
      complex geometry of most medical datasets. We present a general and flexible
      deformable matching framework based on generalized surface flows that efficiently
      tackles these issues through tailored deformation priors and multiresolution
      computations. The value of our approach over existing methods is demonstrated for
      automatic and user-guided cortical registration.

PMID- 18051120
TI  - Real-time nonlinear finite element analysis for surgical simulation using
      graphics processing units.
AB  - Clinical employment of biomechanical modelling techniques in areas of medical
      image analysis and surgical simulation is often hindered by conflicting
      requirements for high fidelity in the modelling approach and high solution
      speeds. We report the development of techniques for high-speed nonlinear finite
      element (FE) analysis for surgical simulation. We employ a previously developed
      nonlinear total Lagrangian explicit FE formulation which offers significant
      computational advantages for soft tissue simulation. However, the key
      contribution of the work is the presentation of a fast graphics processing unit
      (GPU) solution scheme for the FE equations. To the best of our knowledge this
      represents the first GPU implementation of a nonlinear FE solver. We show that
      the present explicit FE scheme is well-suited to solution via highly parallel
      graphics hardware, and that even a midrange GPU allows significant solution speed
      gains (up to 16.4x) compared with equivalent CPU implementations. For the models
      tested the scheme allows real-time solution of models with up to 16000
      tetrahedral elements. The use of GPUs for such purposes offers a cost-effective
      high-performance alternative to expensive multi-CPU machines, and may have
      important applications in medical image analysis and surgical simulation.

PMID- 18051121
TI  - Modeling of needle-tissue interaction using ultrasound-based motion estimation.
AB  - A needle-tissue interaction model is an essential part of every needle insertion
      simulator. In this paper, a new experimental method for the modeling of needle
      tissue interaction is presented. The method consists of measuring needle and
      tissue displacements with ultrasound, measuring needle base forces, and using a
      deformation simulation model to identify the parameters of a needle-tissue
      interaction model. The feasibility of this non-invasive approach was demonstrated
      in an experiment in which a brachytherapy needle was inserted into a prostate
      phantom. Ultrasound radio-frequency data and the time-domain cross-correlation
      method, often used in ultrasound elastography, were used to generate the tissue
      displacement field during needle insertion. A three-parameter force density model
      was assumed for the needle-tissue interaction. With the needle displacement,
      tissue displacement and needle base forces as input data, finite element
      simulations were carried out to adjust the model parameters to achieve a good fit
      between simulated and measured data.

PMID- 18051122
TI  - Modelling intravasation of liquid distension media in surgical simulators.
AB  - We simulate the intravasation of liquid distention media into the systemic
      circulation as it occurs during hysteroscopy and transurethral resection of the
      prostate. A linear network flow model is extended with a correction for non
      newtonian blood behaviour in small vessels and an appropriate handling of vessel
      compliance. We then integrate a fast lookup scheme in order to allow for real
      time simulation. Cutting of tissue is accounted for by adjusting pressure
      boundary conditions for all cut vessels. We investigate the influence of changing
      distention fluid pressure settings and of the position of tissue cuts. Our
      simulation predicts significant intravasation only on the venous side, and just
      in cases when larger veins are cut. The implemented methods allow the realistic
      control of bleeding for short-term and the total resulting intravasation volume
      for long-term complication scenarios. While the simulation is fast enough to
      support real-time training, it is also adequate for explaining intravasation
      effects which were previously observed on a phenomenological level only.

PMID- 18051123
TI  - Registration of cardiac SPECT/CT data through weighted intensity co-occurrence
      priors.
AB  - The introduction of hybrid scanners has greatly increased the popularity of
      molecular imaging techniques. Many clinical applications benefit from combining
      complementary information based on the precise alignment of the two modalities.
      In case the alignment is inaccurate, then this crucial assumption often made for
      subsequent processing steps will be violated. However, this violation may not be
      apparent to the physician. In CT-based attenuation correction (AC) for cardiac
      SPECT/CT data, critical misalignments between SPECT and CT can lead to spurious
      perfusion defects. In this work, we focus on increasing the accuracy of rigid
      volume registration of cardiac SPECT/CT data by using prior knowledge. A new
      weighting scheme for an intensity co-occurrence prior is introduced to assure
      accurate and robust alignment in the local heart region. Experimental results
      demonstrate that the proposed method out-performs mutual information registration
      and shows robustness across a selection of learned distributions acquired from 15
      different patients.

PMID- 18051124
TI  - Prostate implant reconstruction with discrete tomography.
AB  - We developed a discrete tomography method for prostate implant reconstructions
      using only a limited number of X-ray projection images. A 3D voxel volume is
      reconstructed by back-projection and using distance maps generated from the
      projection images. The true seed locations are extracted from the voxel volume
      while false positive seeds are eliminated using a novel optimal geometry coverage
      model. The attractive feature of our method is that it does not require exact
      seed segmentation of the X-ray images and it yields near 100% correct
      reconstruction from only six images with an average reconstruction accuracy of
      0.86 mm (std = 0.46mm).

PMID- 18051125
TI  - A new and general method for blind shift-variant deconvolution of biomedical
      images.
AB  - We present a new method for blind deconvolution of multiple noisy images blurred
      by a shift-variant point-spread-function (PSF). We focus on a setting in which
      several images of the same object are available, and a transformation between
      these images is known. This setting occurs frequently in biomedical imaging, for
      example in microscopy or in medical ultrasound imaging. By using the information
      from multiple observations, we are able to improve the quality of images blurred
      by a shift-variant filter, without prior knowledge of this filter. Also, in
      contrast to other work on blind and shift-variant deconvolution, in our approach
      no parametrization of the PSF is required. We evaluate the proposed method
      quantitatively on synthetically degraded data as well as qualitatively on 3D
      ultrasound images of liver. The algorithm yields good restoration results and
      proves to be robust even in presence of high noise levels in the images.

PMID- 18051126
TI  - Registration of lung tissue between fluoroscope and CT images: determination of
      beam gating parameters in radiotherapy.
AB  - Significant research has been conducted in radiation beam gating technology to
      manage target and organ motions in radiotherapy treatment of cancer patients. As
      more and more on-board imagers are installed onto linear accelerators,
      fluoroscopic imaging becomes readily available at the radiation treatment stage.
      Thus, beam gating parameters, such as beam-on timing and beam-on window can be
      potentially determined by employing image registration between treatment planning
      CT images and fluoroscopic images. We propose a new registration method on
      deformable soft tissue between fluoroscopic images and DRR (Digitally
      Reconstructed Radiograph) images from planning CT images using active shape
      models. We present very promising results of our method applied to 30 clinical
      datasets. These preliminary results show that the method is very robust for the
      registration of deformable soft tissue. The proposed method can be used to
      determine beam-on timing and treatment window for radiation beam gating
      technology, and can potentially greatly improve radiation treatment quality.

PMID- 18051127
TI  - Null point imaging: a joint acquisition/analysis paradigm for MR classification.
AB  - Automatic classification of neurological tissues is a first step to many
      structural analysis pipelines. Most computational approaches are designed to
      extract the best possible classification results out of MR data acquired with
      standard clinical protocols. We observe that the characteristics of the latter
      owe more to the historical circumstances under which they were developed and the
      visual appreciation of the radiographer who acquires the images than to the
      optimality with which they can be classified with an automatic algorithm. We
      submit that better performances could be obtained by considering the acquisition
      and analysis processes conjointly rather than optimising them independently.
      Here, we propose such a joint approach to MR tissue classification in the form of
      a fast MR sequence, which nulls the magnitude and changes the sign of the phase
      at the boundary between tissue types. A simple phase-based thresholding algorithm
      then suffices to segment the tissues. Preliminary results show promises to
      simplify and shorten the overall classification process.

PMID- 18051128
TI  - Characterizing task-related temporal dynamics of spatial activation distributions
      in fMRI BOLD signals.
AB  - We present a new functional magnetic resonance imaging (fMRI) analysis method
      that incorporates both spatial and temporal dynamics of blood-oxygen-level
      dependent (BOLD) signals within a region of interest (ROI). 3D moment descriptors
      are used to characterize the spatial changes in BOLD signals over time. The
      method is tested on fMRI data collected from eight healthy subjects performing a
      bulb-squeezing motor task with their right-hand at various frequencies. Multiple
      brain regions including the left cerebellum, both primary motor cortices (MI),
      both supplementary motor areas (SMA), left prefrontal cortex (PFC), and left
      anterior cingulate cortex (ACC) demonstrate significant task-related changes.
      Furthermore, our method is able to discriminate differences in activation
      patterns at the various task frequencies, whereas using a traditional intensity
      based method, no significant activation difference is detected. This suggests
      that temporal dynamics of the spatial distribution of BOLD signal provide
      additional information regarding task-related activation thus complementing
      conventional intensity-based approaches.

PMID- 18051129
TI  - Contraction detection in small bowel from an image sequence of wireless capsule
      endoscopy.
AB  - This paper describes a method for automatic detection of contractions in the
      small bowel through analyzing Wireless Capsule Endoscopic images. Based on the
      characteristics of contraction images, a coherent procedure that includes
      analyzes of the temporal and spatial features is proposed. For temporal features,
      the image sequence is examined to detect candidate contractions through the
      changing number of edges and an evaluation of similarities between the frames of
      each possible contraction to eliminate cases of low probability. For spatial
      features, descriptions of the directions at the edge pixels are used to determine
      contractions utilizing a classification method. The experimental results show the
      effectiveness of our method that can detect a total of 83% of cases. Thus, this
      is a feasible method for developing tools to assist in diagnostic procedures in
      the small bowel.

PMID- 18051130
TI  - Boundary-specific cost functions for quantitative airway analysis.
AB  - Computed tomography (CT) images of the lungs provide high resolution views of the
      airways. Quantitative measurements such as lumen diameter and wall thickness help
      diagnose and localize airway diseases, assist in surgical planning, and determine
      progress of treatment. Automated quantitative analysis of such images is needed
      due to the number of airways per patient. We present an approach involving
      dynamic programming coupled with boundary-specific cost functions that is capable
      of differentiating inner and outer borders. The method allows for precise
      delineation of the inner lumen and outer wall. The results are demonstrated on
      synthetic data, evaluated on human datasets compared to human operators, and
      verified on phantom CT scans to sub-voxel accuracy.

PMID- 18051131
TI  - Automatic dry eye detection.
AB  - Dry Eye Syndrome is a common disease in the western world, with effects from
      uncomfortable itchiness to permanent damage to the ocular surface. Nevertheless,
      there is still no objective test that provides reliable results. We have
      developed a new method for the automated detection of dry areas in videos taken
      after instilling fluorescein in the tear film. The method consists of a multi
      step algorithm to first locate the iris in each image, then align the images and
      finally analyze the aligned sequence in order to find the regions of interest.
      Since the fluorescein spreads on the ocular surface of the eye the edges of the
      iris are fuzzy making the detection of the iris challenging. We use RANSAC to
      first detect the upper and lower eyelids and then the iris. Then we align the
      images by finding differences in intensities at different scales and using a
      least squares optimization method (Levenberg-Marquardt), to overcome the movement
      of the iris and the camera. The method has been tested on videos taken from
      different patients. It is demonstrated to find the dry areas accurately and to
      provide a measure of the extent of the disease.

PMID- 18051132
TI  - Ultrasound myocardial elastography and registered 3D tagged MRI: quantitative
      strain comparison.
AB  - Ultrasound Myocardial Elastography (UME) and Tagged Magnetic Resonance Imaging
      (tMRI) are two imaging modalities that were developed in the recent years to
      quantitatively estimate the myocardial deformations. Tagged MRI is currently
      considered as the gold standard for myocardial strain mapping in vivo. However,
      despite the low SNR nature of ultrasound signals, echocardiography enjoys the
      widespread availability in the clinic, as well as its low cost and high temporal
      resolution. Comparing the strain estimation performances of the two techniques
      has been of great interests to the community. In order to assess the cardiac
      deformation across different imaging modalities, in this paper, we developed a
      semi-automatic intensity and gradient based registration framework that rigidly
      registers the 3D tagged MRIs with the 2D ultrasound images. Based on the two
      registered modalities, we conducted spatially and temporally more detailed
      quantitative strain comparison of the RF-based UME technique and tagged MRI. From
      the experimental results, we conclude that qualitatively the two modalities share
      similar overall trends. But error and variations in UME accumulate over time.
      Quantitatively tMRI is more robust and accurate than UME.

PMID- 18051133
TI  - Robust kernel methods for sparse MR image reconstruction.
AB  - A major challenge in contemporary magnetic resonance imaging (MRI) lies in
      providing the highest resolution exam possible in the shortest acquisition
      period. Recently, several authors have proposed the use of L1-norm minimization
      for the reconstruction of sparse MR images from highly-undersampled k-space data.
      Despite promising results demonstrating the ability to accurately reconstruct
      images sampled at rates significantly below the Nyquist criterion, the extensive
      computational complexity associated with the existing framework limits its
      clinical practicality. In this work, we propose an alternative recovery framework
      based on homotopic approximation of the L0-norm and extend the reconstruction
      problem to a multiscale formulation. In addition to several interesting
      theoretical properties, practical implementation of this technique effectively
      resorts to a simple iterative alternation between bilteral filtering and
      projection of the measured k-space sample set that can be computed in a matter of
      seconds on a standard PC.

PMID- 18051134
TI  - How do registration parameters affect quantitation of lung kinematics?
AB  - Assessing the quality of motion estimation in the lung remains challenging. We
      approach the problem by imaging isolated porcine lungs within an artificial
      thorax with four-dimensional computed tomography (4DCT). Respiratory kinematics
      are estimated via pairwise non-rigid registration using different metrics and
      image resolutions. Landmarks are manually identified on the images and used to
      assess accuracy by comparing known displacements to the registration-derived
      displacements. We find that motion quantitation becomes less precise as the
      inflation interval between images increases. In addition, its sensitivity to
      image resolution varies anatomically. Mutual information and cross-correlation
      perform similarly, while mean squares is significantly poorer. However, none of
      the metrics compensate for the difficulty of registering over a large inflation
      interval. We intend to use the results of these experiments to more effectively
      and efficiently quantify pulmonary kinematics in future, and to explore
      additional parameter combinations.

PMID- 18051135
TI  - Diffuse parenchymal lung diseases: 3D automated detection in MDCT.
AB  - Characterization and quantification of diffuse parenchymal lung disease (DPLD)
      severity using MDCT, mainly in interstitial lung diseases and emphysema, is an
      important issue in clinical research for the evaluation of new therapies. This
      paper develops a 3D automated approach for detection and diagnosis of DPLDs
      (emphysema, fibrosis, honeycombing, ground glass). The proposed methodology
      combines multi-resolution image decomposition based on 3D morphological
      filtering, and graph-based classification for a full characterization of the
      parenchymal tissue. The very promising results obtained on a small patient
      database are good premises for a near implementation and validation of the
      proposed approach in clinical routine.

PMID- 18051136
TI  - Unsupervised reconstruction of a patient-specific surface model of a proximal
      femur from calibrated fluoroscopic images.
AB  - In this paper, we present an unsupervised 2D/3D reconstruction scheme combining a
      parameterized multiple-component geometrical model and a point distribution
      model, and show its application to automatically reconstruct a surface model of a
      proximal femur from a limited number of calibrated fluoroscopic images with no
      user intervention at all. The parameterized multiple-component geometrical model
      is regarded as a simplified description capturing the geometrical features of a
      proximal femur. Its parameters are optimally and automatically estimated from the
      input images using a particle filter based inference method. The estimated
      geometrical parameters are then used to initialize a point distribution model
      based 2D/3D reconstruction scheme for an accurate reconstruction of a surface
      model of the proximal femur. We designed and conducted in vitro and in vivo
      experiments to compare the present unsupervised reconstruction scheme to a
      supervised one. An average mean error of 1.2 mm was found when the supervised
      reconstruction scheme was used. It increased to 1.3 mm when the unsupervised one
      was used. However, the unsupervised reconstruction scheme has the advantage of
      elimination of user intervention, which holds the potential to facilitate the
      application of the 2D/3D reconstruction in surgical navigation.

PMID- 18051137
TI  - A new method for spherical object detection and its application to computer aided
      detection of pulmonary nodules in CT images.
AB  - A novel method called local shape controlled voting has been developed for
      spherical object detection in 3D voxel images. By introducing local shape
      properties into the voting procedure of normal overlap, the proposed method
      improves the capability of differentiating spherical objects from other
      structures, as the normal overlap technique only measures the 'density' of normal
      overlapping, while how the normals are distributed in 3D is not discovered. The
      proposed method was applied to computer aided detection of pulmonary nodules
      based on helical CT images. Experiments showed that this method attained a better
      performance compared to the original normal overlap technique.

PMID- 18051138
TI  - Global medical shape analysis using the Laplace-Beltrami spectrum.
AB  - This paper proposes to use the Laplace-Beltrami spectrum (LBS) as a global shape
      descriptor for medical shape analysis, allowing for shape comparisons using
      minimal shape preprocessing: no registration, mapping, or remeshing is necessary.
      The discriminatory power of the method is tested on a population of female
      caudate shapes of normal control subjects and of subjects with schizotypal
      personality disorder.

PMID- 18051139
TI  - Real-time tracking of the left ventricle in 3D echocardiography using a state
      estimation approach.
AB  - In this paper we present a framework for real-time tracking of deformable
      contours in volumetric datasets. The framework supports composite deformation
      models, controlled by parameters for contour shape in addition to global pose.
      Tracking is performed in a sequential state estimation fashion, using an extended
      Kalman filter, with measurement processing in information space to effectively
      predict and update contour deformations in real-time. A deformable B-spline
      surface coupled with a global pose transform is used to model shape changes of
      the left ventricle of the heart. Successful tracking of global motion and local
      shape changes without user intervention is demonstrated on a dataset consisting
      of 21 3D echocardiography recordings. Real-time tracking using the proposed
      approach requires a modest CPU load of 13% on a modern computer. The segmented
      volumes compare to a semi-automatic segmentation tool with 95% limits of
      agreement in the interval 4.1 +/- 24.6 ml (r = 0.92).

PMID- 18051140
TI  - Vessel and intracranial aneurysm segmentation using multi-range filters and local
      variances.
AB  - Segmentation of vessels and brain aneurysms on non-invasive and flow-sensitive
      phase contrast magnetic resonance angiographic (PCMRA) images is essential in the
      detection of vascular diseases, in particular, intracranial aneurysms. In this
      paper, we devise a novel method based on multi-range filters and local variances
      to perform segmentation of vessels and intracranial aneurysms on PCMRA images.
      The proposed method is validated and compared using a synthetic and numerical
      image volume and four clinical cases. It is experimentally shown that the
      proposed method is capable of segmenting vessels and aneurysms with various sizes
      on PCMRA images.

PMID- 18051141
TI  - Fully automatic segmentation of the hippocampus and the amygdala from MRI using
      hybrid prior knowledge.
AB  - The segmentation of macroscopically ill-defined and highly variable structures,
      such as the hippocampus Hc and the amygdala Am, from MRI requires specific
      constraints. Here, we describe and evaluate a hybrid segmentation method that
      uses knowledge derived from a probabilistic atlas and from anatomical landmarks
      based on stable anatomical characteristics of the structures. Combined in a
      previously published semi-automatic segmentation method, they lead to a fast,
      robust and accurate fully automatic segmentation of Hc and Am. The probabilistic
      atlas was built from 16 young controls and registered with the "unified
      segmentation" of SPM5. The algorithm was quantitatively evaluated with respect to
      manual segmentation on two MRI datasets: the 16 young controls, with a leave-one
      out strategy, and a mixed cohort of 8 controls and 15 subjects with epilepsy with
      variable hippocampal sclerosis. The segmentation driven by hybrid knowledge leads
      to greatly improved results compared to that obtained by registration of the
      thresholded atlas alone: mean overlap for Hc on the 16 young controls increased
      from 78% to 87% (p < 0.001) and on the mixed cohort from 73% to 82% (p < 0.001)
      while the error on volumes decreased from 10% to 7% (p < 0.005) and from 18% to
      8% (p < 0.001), respectively. Automatic results were better than the semi
      automatic results: for the 16 young controls, average overlap increased from 84%
      to 87% (p < 0.001) for Hc and from 81% to 84% (p < 0.002) for Am, with equivalent
      improvements in volume error.

PMID- 18051142
TI  - Clinical neonatal brain MRI segmentation using adaptive nonparametric data models
      and intensity-based Markov priors.
AB  - This paper presents a Bayesian framework for neonatal brain-tissue segmentation
      in clinical magnetic resonance (MR) images. This is a challenging task because of
      the low contrast-to-noise ratio and large variance in both tissue intensities and
      brain structures, as well as imaging artifacts and partial-volume effects in
      clinical neonatal scanning. We propose to incorporate a spatially adaptive
      likelihood model using a data-driven nonparametric statistical technique. The
      method initially learns an intensity-based prior, relying on the empirical Markov
      statistics from training data, using fuzzy nonlinear support vector machines
      (SVM). In an iterative scheme, the models adapt to spatial variations of image
      intensities via nonparametric density estimation. The method is effective even in
      the absence of anatomical atlas priors. The implementation, however, can
      naturally incorporate probabilistic atlas priors and Markov-smoothness priors to
      impose additional regularity on segmentation. The maximum-a-posteriori (MAP)
      segmentation is obtained within a graph-cut framework. Cross validation on
      clinical neonatal brain-MR images demonstrates the efficacy of the proposed
      method, both qualitatively and quantitatively.

PMID- 18051143
TI  - Active-contour-based image segmentation using machine learning techniques.
AB  - We introduce a non-linear shape prior for the deformable model framework that we
      learn from a set of shape samples using recent manifold learning techniques. We
      model a category of shapes as a finite dimensional manifold which we approximate
      using Diffusion maps. Our method computes a Delaunay triangulation of the reduced
      space, considered as Euclidean, and uses the resulting space partition to
      identify the closest neighbors of any given shape based on its Nystrom extension.
      We derive a non-linear shape prior term designed to attract a shape towards the
      shape prior manifold at given constant embedding. Results on shapes of ventricle
      nuclei demonstrate the potential of our method for segmentation tasks.

PMID- 18051144
TI  - Methods for inverting dense displacement fields: evaluation in brain image
      registration.
AB  - In medical image analysis there is frequently a need to invert dense displacement
      fields which map one image space to another. In this paper we describe inversion
      techniques and determine their accuracy in the context of 18 inter-subject brain
      image registrations. Scattered data interpolation (SDI) is used to initialise
      locally and globally consistent iterative techniques. The inverse-consistency
      error, E(IC) is computed over the whole image and over 10 specific brain regions.
      SDI produced good results with mean (max) E(IC) approximately 0.02mm (2.0mm).
      Both iterative method produced mean errors of approximately 0.005mm but the
      globally consistent method resulted in a smaller maximum error (1.9mm compared
      with 1.4mm). The largest errors were in the cerebral cortex with large outlier
      errors in the ventricles. Simple iterative techniques are, on this evidence, able
      to produce reasonable estimates of inverse displacement fields provided there is
      good initialisation.

PMID- 18051145
TI  - Registration of high angular resolution diffusion MRI images using 4th order
      tensors.
AB  - Registration of Diffusion Weighted (DW)-MRI datasets has been commonly achieved
      to date in literature by using either scalar or 2nd-order tensorial information.
      However, scalar or 2nd-order tensors fail to capture complex local tissue
      structures, such as fiber crossings, and therefore, datasets containing fiber
      crossings cannot be registered accurately by using these techniques. In this
      paper we present a novel method for non-rigidly registering DW-MRI datasets that
      are represented by a field of 4th-order tensors. We use the Hellinger distance
      between the normalized 4th-order tensors represented as distributions, in order
      to achieve this registration. Hellinger distance is easy to compute, is scale and
      rotation invariant and hence allows for comparison of the true shape of
      distributions. Furthermore, we propose a novel 4th-order tensor re-transformation
      operator, which plays an essential role in the registration procedure and shows
      significantly better performance compared to the re-orientation operator used in
      literature for DTI registration. We validate and compare our technique with other
      existing scalar image and DTI registration methods using simulated diffusion MR
      data and real HARDI datasets.

PMID- 18051146
TI  - Non-rigid image registration using graph-cuts.
AB  - Non-rigid image registration is an ill-posed yet challenging problem due to its
      supernormal high degree of freedoms and inherent requirement of smoothness. Graph
      cuts method is a powerful combinatorial optimization tool which has been
      successfully applied into image segmentation and stereo matching. Under some
      specific constraints, graph-cuts method yields either a global minimum or a local
      minimum in a strong sense. Thus, it is interesting to see the effects of using
      graph-cuts in non-rigid image registration. In this paper, we formulate non-rigid
      image registration as a discrete labeling problem. Each pixel in the source image
      is assigned a displacement label (which is a vector) indicating which position in
      the floating image it is spatially corresponding to. A smoothness constraint
      based on first derivative is used to penalize sharp changes in displacement
      labels across pixels. The whole system can be optimized by using the graph-cuts
      method via alpha-expansions. We compare 2D and 3D registration results of our
      method with two state-of-the-art approaches. It is found that our method is more
      robust to different challenging non-rigid registration cases with higher
      registration accuracy.

PMID- 18051147
TI  - Probabilistic speckle decorrelation for 3D ultrasound.
AB  - Recent developments in freehand 3D ultrasound (US) have shown how image
      registration and speckle decorrelation methods can be used for 3D reconstruction
      instead of relying on a tracking device. Estimating elevational separation
      between untracked US images using speckle decorrelation is error prone due to the
      uncertainty that plagues the correlation measurements. In this paper, using
      maximum entropy estimation methods, the uncertainty is directly modeled from the
      calibration data normally used to estimate an average decorrelation curve.
      Multiple correlation measurements can then be fused within a maximum likelihood
      estimation framework in order to reduce the drift in elevational pose estimation
      over large image sequences. The approach is shown to be effective through
      empirical results on simulated and phantom US data.

PMID- 18051148
TI  - De-enhancing the dynamic contrast-enhanced breast MRI for robust registration.
AB  - Dynamic enhancement causes serious problems for registration of contrast enhanced
      breast MRI, due to variable uptakes of agent on different tissues or even same
      tissues in the breast. We present an iterative optimization algorithm to de
      enhance the dynamic contrast-enhanced breast MRI and then register them for
      avoiding the effects of enhancement on image registration. In particular, the
      spatially varying enhancements are modeled by a Markov Random Field, and
      estimated by a locally smooth function with boundaries using a graph cut
      algorithm. The de-enhanced images are then registered by conventional B-spline
      based registration algorithm. These two steps benefit from each other and are
      repeated until the results converge. Experimental results show that our two-step
      registration algorithm performs much better than conventional mutual information
      based registration algorithm. Also, the effects of tumor shrinking in the
      conventional registration algorithms can be effectively avoided by our
      registration algorithm.

PMID- 18051150
TI  - Robust computation of mutual information using spatially adaptive meshes.
AB  - We present a new method for the fast and robust computation of information
      theoretic similarity measures for alignment of multi-modality medical images. The
      proposed method defines a non-uniform, adaptive sampling scheme for estimating
      the entropies of the images, which is less vulnerable to local maxima as compared
      to uniform and random sampling. The sampling is defined using an octree partition
      of the template image, and is preferable over other proposed methods of non
      uniform sampling since it respects the underlying data distribution. It also
      extends naturally to a multi-resolution registration approach, which is commonly
      employed in the alignment of medical images. The effectiveness of the proposed
      method is demonstrated using both simulated MR images obtained from the BrainWeb
      database and clinical CT and SPECT images.

PMID- 18051149
TI  - Deformable density matching for 3D non-rigid registration of shapes.
AB  - There exists a large body of literature on shape matching and registration in
      medical image analysis. However, most of the previous work is focused on matching
      particular sets of features--point-sets, lines, curves and surfaces. In this
      work, we forsake specific geometric shape representations and instead seek
      probabilistic representations--specifically Gaussian mixture models--of shapes.
      We evaluate a closed-form distance between two probabilistic shape
      representations for the general case where the mixture models differ in variance
      and the number of components. We then cast non-rigid registration as a deformable
      density matching problem. In our approach, we take one mixture density onto
      another by deforming the component centroids via a thin-plate spline (TPS) and
      also minimizing the distance with respect to the variance parameters. We validate
      our approach on synthetic and 3D arterial tree data and evaluate it on 3D
      hippocampal shapes.

PMID- 18051151
TI  - Shape analysis using a point-based statistical shape model built on
      correspondence probabilities.
AB  - A fundamental problem when computing statistical shape models is the
      determination of correspondences between the instances of the associated data
      set. Often, homologies between points that represent the surfaces are assumed
      which might lead to imprecise mean shape and variability results. We propose an
      approach where exact correspondences are replaced by evolving correspondence
      probabilities. These are the basis for a novel algorithm that computes a
      generative statistical shape model. We developed an unified MAP framework to
      compute the model parameters ('mean shape' and 'modes of variation') and the
      nuisance parameters which leads to an optimal adaption of the model to the set of
      observations. The registration of the model on the instances is solved using the
      Expectation Maximization--Iterative Closest Point algorithm which is based on
      probabilistic correspondences and proved to be robust and fast. The alternated
      optimization of the MAP explanation with respect to the observation and the
      generative model parameters leads to very efficient and closed-form solutions for
      (almost) all parameters. Experimental results on brain structure data sets
      demonstrate the efficiency and well-posedness of the approach. The algorithm is
      then extended to an automatic classification method using the k-means clustering
      and applied to synthetic data as well as brain structure classification problems.

PMID- 18051152
TI  - Robust autonomous model learning from 2D and 3D data sets.
AB  - In this paper we propose a weakly supervised learning algorithm for appearance
      models based on the minimum description length (MDL) principle. From a set of
      training images or volumes depicting examples of an anatomical structure,
      correspondences for a set of landmarks are established by group-wise
      registration. The approach does not require any annotation. In contrast to
      existing methods no assumptions about the topology of the data are made, and the
      topology can change throughout the data set. Instead of a continuous
      representation of the volumes or images, only sparse finite sets of interest
      points are used to represent the examples during optimization. This enables the
      algorithm to efficiently use distinctive points, and to handle texture variations
      robustly. In contrast to standard elasticity based deformation constraints the
      MDL criterion accounts for systematic deformations typical for training sets
      stemming from medical image data. Experimental results are reported for five
      different 2D and 3D data sets.

PMID- 18051153
TI  - On simulating subjective evaluation using combined objective metrics for
      validation of 3D tumor segmentation.
AB  - In this paper, we present a new segmentation evaluation method that can simulate
      radiologist's subjective assessment of 3D tumor segmentation in CT images. The
      method uses a new metric defined as a linear combination of a set of commonly
      used objective metrics. The weighing parameters of the linear combination are
      determined by maximizing the rank correlation between radiologist's subjective
      rating and objective measurements. Experimental results on 93 lesions demonstrate
      that the new composite metric shows better performance in segmentation evaluation
      than each individual objective metric. Also, segmentation rating using the
      composite metric compares well with radiologist's subjective evaluation. Our
      method has the potential to facilitate the development of new tumor segmentation
      algorithms and assist large scale segmentation evaluation studies.

PMID- 18051154
TI  - Detection and segmentation of pathological structures by the extended graph
      shifts algorithm.
AB  - We propose an extended graph-shifts algorithm for image segmentation and
      labeling. This algorithm performs energy minimization by manipulating a dynamic
      hierarchical representation of the image. It consists of a set of moves occurring
      at different levels of the hierarchy where the types of move, and the level of
      the hierarchy, are chosen automatically so as to maximally decrease the energy.
      Extended graph-shifts can be applied to a broad range of problems in medical
      imaging. In this paper, we apply extended graph-shifts to the detection of
      pathological brain structures: (i) segmentation of brain tumors, and (ii)
      detection of multiple sclerosis lesions. The energy terms in these tasks are
      learned from training data by statistical learning algorithms. We demonstrate
      accurate results, precision and recall in the order of 93%, and also show that
      the algorithm is computationally efficient, segmenting a full 3D volume in about
      one minute.

PMID- 18051155
TI  - Cutting tool system to minimize soft tissue damage for robot-assisted minimally
      invasive orthopedic surgery.
AB  - Minimally invasive surgery in orthopedic field is considered to be a challenging
      problem with a milling robot. One objective of this study is to minimize
      collision of the cutting tool with soft tissue. The authors have developed a
      robot with redundant axis to avoid the collision so far. Some important
      components are modeled based on physical requirements, and a geometric
      optimization approach based on the model has been also proposed to improve
      performance. In this paper, a protective mechanism to cover the non-working part
      of the cutting edge is proposed to avoid soft tissue damage. Hardware and
      software have been developed for this application and the effectiveness of this
      technique was evaluated with urethane bone.

PMID- 18051156
TI  - Shear resonance behavior of single-domain PZN-PT single crystals.
AB  - The shear resonance behavior of rectangular-shaped samples of single-domain PZN
      PT single crystal samples of 3m symmetry and having three faces parallel to the
      (111), (112), and (110) crystal planes has been examined. Sample geometries with
      separable resonance peaks are identified, which give shear properties consistent
      with 3m symmetry, namely, k15 approximately k24 and d15 approximately d24. Sample
      geometries with inseparable resonance peaks are also distinguished. The latter
      sample geometries are not suitable for shear property characterization of
      piezoelectric single crystals of 3m symmetry as the broad coupled resonance peak
      often results in inflated k15 and d15 values.

PMID- 18051157
TI  - Application of RF varactor using Ba(x)Sr(1-x)TiO3/TiO2/HR-Si substrate for
      reconfigurable radio.
AB  - In this paper, the potential feasibility of integrating Ba(x)Sr(1-x)TiO3 (BST)
      films into Si wafer by adopting tunable interdigital capacitor (IDC) with TiO2
      thin film buffer layer and a RF tunable active bandpass filter (BPF) using BST
      based capacitor are proposed. TiO2 as a buffer layer is grown onto Si substrate
      by atomic layer deposition (ALD) and the interdigital capacitor on BST(500
      nm)/TiO2 (50 nm)/HR-Si is fabricated. BST interdigital tunable capacitor
      integrated on HR-Si substrate with high tunability and low loss tangent are
      characterized for their microwave performances. BST/TiO2/HR-Si IDC shows much
      enhanced tunability values of 40% and commutation quality factor (CQF) of 56.71.
      A resonator consists of an active capacitance circuit together with a BST
      varactor. The active capacitor is made of a field effect transistor (FET) that
      exhibits negative resistance as well as capacitance. The measured second order
      active BPF shows bandwidth of 110 MHz, insertion loss of about 1 dB at the 1.81
      GHz center frequency and tuning frequency of 230 MHz (1.81-2.04 GHz).

PMID- 18051159
TI  - Elasticity imaging using conventional and high-frame rate ultrasound imaging:
      experimental study.
AB  - High-frame rate ultrasound imaging is necessary to track fast deformation in
      ultrasound elasticity imaging, but the image quality may be degraded. Previously,
      we investigated the performance of strain imaging using numerical models of
      conventional and ultrafast ultrasound imaging techniques. In this paper, we
      performed experimental studies to quantitatively evaluate the strain images and
      elasticity maps obtained using conventional and high frame rate ultrasound
      imaging methods. The experiments were carried out using point target and tissue
      mimicking phantoms. The experimental results were compared with the results of
      numerical simulation. Our experimental studies confirm that the signal-to-noise
      ratio (SNR), contrast-to-noise ratio (CNR), and axial/lateral resolution of the
      displacement and strain images acquired using high-frame rate ultrasound imaging
      are slightly lower but comparable with those obtained using conventional imaging.
      Furthermore, the quality of elasticity images also exhibits similar trends. Thus,
      high-frame rate ultrasound imaging can be used reliably for static elasticity
      imaging to capture the internal tissue motion if the frame rate is critical.

PMID- 18051158
TI  - Theoretical quality assessment of myocardial elastography with in vivo
      validation.
AB  - Myocardial elastography (ME), a radio frequency (RF)-based speckle tracking
      technique with one-dimensional (1-D) cross correlation and novel recorrelation
      methods in a 2-D search was proposed to estimate and fully image 2-D transmural
      deformation field and to detect abnormal cardiac function. A theoretical
      framework was first developed in order to evaluate the performance of 2-D
      myocardial elastography based on a previously developed 3-D finite-element model
      of the canine left ventricle. A normal (control) and an ischemic (left
      circumflex, LCx) model, which more completely represented myocardial deformation
      than a kinematic model, were considered. A 2-D convolutional image formation
      model was first used to generate RF signals for quality assessment of ME in the
      normal and ischemic cases. A 3-D image formation model was further developed to
      investigate the effect of the out-of-plane motion on the 2-D, in-plane motion
      estimation. Both orthogonal, in-plane displacement components (i.e., lateral and
      axial) between consecutive RF frames were iteratively estimated. All the
      estimated incremental 2-D displacements from end-diastole (ED) to end-systole
      (ES) were then accumulated to acquire the cumulative 2-D displacements, which
      were further used to calculate the cumulative 2-D systolic finite strains.
      Furthermore, the cumulative systolic radial and circumferential strains, which
      were angle- and frame-rate independent, were obtained from the 2-D finite-strain
      components and imaged in full view to detect the ischemic region. We also
      explored the theoretical understanding of the limitations of our technique for
      the accurate depiction of disease and validated it in vivo against tagged
      magnetic resonance imaging (tMRI) in the case of a normal human myocardium in a 2
      D short-axis (SA) echocardiographic view. The theoretical framework succeeded in
      demonstrating that the 2-D myocardial elastography technique was a reliable tool
      for the complete estimation and depiction of the in-plane myocardial deformation
      field as well as for accurate identification of pathological mechanical function
      using established finite-element, left-ventricular canine models. In a
      preliminary study, the 2-D myocardial elastography was shown capable of imaging
      myocardial deformation comparable to equivalent tMRI estimates in a clinical
      setting.

PMID- 18051160
TI  - Mechanical properties of single cells by high-frequency time-resolved acoustic
      microscopy.
AB  - In this paper, we describe a new, high-frequency, time-resolved scanning acoustic
      microscope developed for studying dynamical processes in biological cells. The
      new acoustic microscope operates in a time-resolved mode. The center frequency is
      0.86 GHz, and the pulse duration is 5 ns. With such a short pulse, layers thicker
      than 3 microm can be resolved. For a cell thicker than 3 microm, the front echo
      and the echo from the substrate can be distinguished in the signal. Positions of
      the first and second pulses are used to determine the local impedance of the cell
      modeled as a thin liquid layer that has spatial variations in its elastic
      properties. The low signal-to-noise ratio in the acoustical images is increased
      for image generation by averaging the detected radio frequency signal over 10
      measurements at each scanning point. In conducting quantitative measurements of
      the acoustic parameters of cells, the signal can be averaged over 2000
      measurements. This approach enables us to measure acoustical properties of a
      single HeLa cell in vivo and to derive elastic parameters of subcellular
      structures. The value of the sound velocity inside the cell (1534.5 +/- 33.6 m/s)
      appears to be only slightly higher than that of the cell medium (1501 m/s).

PMID- 18051161
TI  - Fast B-flow imaging: a method for improving frame rate in Golay coded B-flow
      imaging.
AB  - A technique for Golay coded B-flow imaging, called fast B-flow imaging, has been
      developed. This technique improves the frame rate of Golay coded B-flow imaging.
      In this technique, three instead of four input pulses are used to produce each
      scan line. A standard Golay pulse-pair is used as two of the three inputs, and
      pulse compression is performed upon receive returning the echoes from stationary
      (tissue) objects in the image. The third input is a repetition of one of the
      first two inputs. Upon receive, this pulse is cross correlated with an inverted
      copy of its input pulse. Addition of the cross-correlated signals produced from
      the identical input pulses results in the cancellation of the strong tissue
      echoes, and enables visualization of the weaker/moving blood echoes. Combining a
      small fraction of the tissue echoes with the weaker blood echoes allows both to
      be visualized in the same gray scale image. By using three instead of four input
      pulses, this technique can achieve a frame rate improvement of 33% compared with
      standard Golay coded B-flow imaging, with some loss in signal-to-noise ratio. The
      impact of axial and lateral motion on these techniques is examined. A
      quantitative comparison of both techniques is presented.

PMID- 18051162
TI  - Radial modulation of microbubbles for ultrasound contrast imaging.
AB  - Over the past few years, extensive research has been carried out in the field of
      ultrasound contrast imaging. In addition to the development of new types of
      ultrasound contrast agents, various imaging methods dedicated to contrast agents
      have been introduced, and some of them are now commercially available. In this
      study, we present results of an imaging technique that is capable of detecting
      echoes from microbubbles and eliminating those emanating from nonoscillating
      structures (tissue), thereby enhancing contrast imaging. The method is based on
      mixing a low frequency (LF) modulator signal and a high frequency (HF) imaging
      signal to effectively modulate the size of the contrast microbubble through its
      volumetric oscillations using the LF signal and to probe the radial motion using
      the HF imaging signal. To evaluate the performances and limitations of the
      method, high-speed optical observations and acoustic measurements were carried
      out on soft-shelled microbubbles. The results showed that, by incorporating the
      modulator signal, the bubbles respond differently compared to the HF excitation
      alone. The decorrelation between the signals obtained at the compression and
      expansion phase of the modulator signal is significantly high to be used as a
      parameter to detect contrast microbubbles and discriminate them from tissue. The
      echo received from a solid reflector shows identical responses during the
      compression and rarefaction phase of the LF signal. In conclusion, these results
      demonstrate the feasibility of this fully linear approach for improving the
      contrast detection.

PMID- 18051163
TI  - Sensitive ultrasonic delineation of steroid treatment in living dystrophic mice
      with energy-based and entropy-based radio frequency signal processing.
AB  - Duchenne muscular dystrophy is a severe wasting disease, involving replacement of
      necrotic muscle tissue by fibrous material and fatty infiltrates. One primary
      animal model of this human disease is the X chromosome-linked mdx strain of mice.
      The goals of the present work were to validate and quantify the capability of
      both energy and entropy metrics of radio-frequency ultrasonic backscatter to
      differentiate among normal, dystrophic, and steroid-treated skeletal muscle in
      the mdx model. Thirteen 12-month-old mice were blocked into three groups: 4
      treated mdx-dystrophic that received daily subcutaneous steroid (prednisolone)
      treatment for 14 days, 4 positive-control mdx-dystrophic that received saline
      injections for 14 days, and 5 negative-control animals. Biceps muscle of each
      animal was imaged in vivo using a 40-MHz center frequency transducer in
      conjunction with a Vevo-660 ultrasound system. Radio-frequency data were acquired
      (1 GHz, 8 bits) corresponding to a sequence of transverse images, advancing the
      transducer from "shoulder" to "elbow" in 100-micron steps. Data were processed to
      generate both "integrated backscatter" (log energy), and "entropy" (information
      theoretic receiver, H(f)) representations. Analyses of the integrated-backscatter
      values delineated both treated-and untreated-mdx biceps from normal controls (p <
      0.01). Complementary analyses of the entropy images differentiated the steroid
      treated and positive-control mdx groups (p < 0.01). To our knowledge, this study
      represents the first reported use of quantitative ultrasonic characterization of
      skeletal muscle in mdx mice. Successful differentiation among dystrophic, steroid
      treated, and normal tissues suggests the potential for local noninvasive
      monitoring of disease severity and therapeutic effects.

PMID- 18051164
TI  - A two-dimensional CVIB imaging system with a snake-based tracking algorithm.
AB  - Quantitative ultrasound tissue characterization based on integrated backscatter
      (IB) has shown great potential in detecting myocardial ischemia. The magnitude of
      the cyclic variation in IB (CVIB) has recently been considered as one of the most
      promising parameters in assessing regional myocardial contractile performance.
      Our laboratory previously developed a novel ultrasonic fusion imaging method
      based on the CVIB. However, the major problem for clinical applications of this
      technique and other existing analytical methods based on IB is that the
      myocardial tissue can't be traced effectively without the cardiologist's
      intervention. In order to solve this problem, this paper presents a snake-based
      tracking algorithm to trace myocardial tissue automatically. A mathematical
      method is also introduced to extend the application of the snake model for
      detecting non-closed contours. The system developed in our previous research was
      redesigned to synchronize the radio frequency signal, the electrocardiographic
      signal, and the video signal, which allows verification of the system. Our
      results suggest that the system using the auto-tracking method increases the
      accuracy of detecting myocardial ischemia.

PMID- 18051165
TI  - Two-dimensional localization with a single diffuse ultrasound field excitation.
AB  - Traditional ultrasound imaging methods rely on the bandwidth and center frequency
      of transduction to achieve axial and radial image resolution, respectively. In
      this study, a new modality for spatially localizing scattering targets in a two
      dimensional field is presented. In this method, the bandwidth of field excitation
      is high, and the center frequency is lowered such that the corresponding
      wavelengths are substantially larger than the target profiles. Furthermore, full
      two-dimensional field measurements are obtained with single send-receive
      sequences, demonstrating a substantial simplification of the traditional scanning
      techniques. Field reconstruction is based on temporal-spectral cross-correlations
      between measured backscatter data and a library of region of interest (ROI)
      backscatter data measured a priori. The transducer design is based upon a wedge
      shaped geometry, which was shown to yield spatially frequency-separated
      bandwidths of up to 156% with center frequencies of 1.38 MHz. Initial results
      with these send-and-receive transducer parameters and cylindrical reflection
      targets in a 10-mm x 10-mm ROI demonstrate two-dimensional target localization to
      within 0.5 mm. Spatial localization of point scatterers is demonstrated for
      single and multiple scattering sites.

PMID- 18051166
TI  - A novel pyroelectric method of determining ultrasonic transducer output power:
      device concept, modeling, and preliminary studies.
AB  - This paper describes a new thermally based method of monitoring acoustic output
      power generated by ultrasonic transducers. Its novelty lies in the exploitation
      of the pyroelectric properties of a thin membrane of polyvinylidene fluoride
      (PVDF). The membrane is backed by a thick layer of polyurethane rubber that is
      extremely attenuating to ultrasound, with the result that the majority of the
      applied acoustic power is absorbed within a few millimeters of the membrane
      backing interface. Through the resultant rapid increase in temperature of the
      membrane, a voltage is generated across its electrodes whose magnitude is
      proportional to the rate of change of temperature with respect to time. Changes
      in the pyroelectric voltage generated by switching the transducer ON and OFF are
      related to the acoustic power delivered by the transducer. Features of the
      technique are explored through the development of a simple one-dimensional model.
      An experimental evaluation of the potential secondary measurement technique is
      also presented, covering the frequency range 1 to 5 MHz, for delivered powers up
      to a watt. Predictions of the sensor output signals, as well as the frequency
      dependent sensitivity, are in good agreement with observation. The potential of
      the new method as a simple, rapid means of providing traceable ultrasonic power
      measurements is outlined.

PMID- 18051167
TI  - The thermal effect of metal electrodes on thickness-shear vibrations of crystal
      plates.
AB  - The effectiveness of theoretical approaches based on the initial thermal field on
      vibrations elastic solids has been demonstrated by a series of analyses
      concerning the thermal behavior of crystal resonators with results in good
      agreement with measurements. These equations have been implemented in a finite
      element method in addition to simple analytical solutions we are familiar with.
      Starting with an infinite plate under a temperature increase in both crystal and
      metal layers, the frequency equation based on incremental thermal field
      formulation is obtained and solved analytically for thickness-shear vibrations
      with electrodes of different metals and configuration. Numerical examples show
      that the thermal effect of thicker electrodes on frequency-temperature relations
      of thickness-shear vibrations of AT-cut quartz crystal plates are generally
      positive and should be considered in the design process.

PMID- 18051168
TI  - A stator for a self-running, ultrasonically-levitated sliding stage.
AB  - Here we propose a self-running, ultrasonically-levitated sliding stage and
      investigate the levitation and propulsion characteristics of its stator. The
      stator consists of two aluminum beams and four PZT plates, which have two-paired
      bimorph configurations. A flexural standing wave was generated along the beam by
      applying an input voltage to the PZTs, and the stator could be levitated from a
      flat substrate by the acoustic radiation force generated by its own vibrating
      beam. The size of the stator was optimized using finite-element analysis (FEA) to
      maximize the vibration displacement amplitude of the beam. The flexural vibration
      modes at 24.3 and 102 kHz were the most prominent vibration modes having large
      displacement amplitudes. The stator was levitated at 23.2 and 96.1 kHz, which are
      close to the frequencies predicted by the FEA results. A standing wave was
      observed along the beam. The experimental and the simulated results showed good
      agreement. The levitation distance h was measured by varying the vibration
      displacement amplitude of the beam u, and was found to be proportional to u. When
      a traveling wave was excited along the beam by controlling the temporal phase
      difference of the two transducers, the stator could be made to hover and to move
      in the opposite direction to the traveling wave. The stator moved in the positive
      direction when the phase difference was in the ranges 0 degrees to 200 degrees
      and 310 degrees to 360 degrees, and in the negative direction when the phase
      difference was between 220 degrees and 260 degrees.

PMID- 18051169
TI  - A single probe spatial averaging technique for guided waves and its application
      to surface wave rail inspection.
AB  - The nondestructive testing of structures using guided waves requires systems with
      high mode selectivity. Usually this is achieved with relatively complex probes
      comprising multiple transducer rings or arrays. For the rapid inspection of very
      long structures with only partial access to the waveguide, this may not be a
      viable solution. In this paper we present a very flexible alternative whereby a
      simple robust probe is scanned along the wave guide, and the acquired scan data
      is used for customizing the mode selectivity at the postprocessing stage. The
      characteristics of this spatial averaging method are discussed using a simple
      analytical model and compared to an existing linear array technique. The mode
      selectivity is found to be mainly limited by the uncertainty of the phase
      velocity assumed for the mode of interest. The method was successfully applied to
      surface wave rail inspection and was found to suppress unwanted modes very
      efficiently.

PMID- 18051170
TI  - Ultrasonic scattering in chocolate and model systems containing sucrose,
      tripalmitin and olive oil.
AB  - Ultrasonic measurements of attenuation versus frequency were made on model
      systems comprising olive oil, sucrose, and tripalmitin to represent the
      constituents of chocolate. Corresponding measurements also were made on chocolate
      flowing in a pipeline at a pilot plant where the temperature, pressure, and
      temper of the chocolate were precisely controlled and monitored. Experimental
      results combined with simulation studies indicate that the effect of ultrasonic
      scattering from tripalmitin crystals in olive oil is modified by the addition of
      sucrose crystals at a high concentration. It is proposed that the presence of
      seed crystals in chocolate (temper) cannot be detected ultrasonically in the
      practical measurement range 1-12 MHz due to a similar process.

PMID- 18051171
TI  - Circuital model for the analysis of the piezoelectric response of A1N films using
      SAW filters.
AB  - In this paper we describe a method to assess the piezoelectric response of a
      piezoelectric thin film deposited on a conductive substrate. It is based on
      analyzing the frequency response of a surface acoustic wave (SAW) filter made on
      the piezoelectric thin film. For this analysis, we use a circuital model that
      takes into account the theoretical response of the ideal filter along with all
      the external and internal parasitic effects that deteriorate the response. Using
      this model, we can obtain the electromechanical coupling factor of the
      piezoelectric material (k2m) with good accuracy. If parasitic effects are not
      considered, k2m can be underestimated by a factor of up to 20. We have tested our
      model using SAW filters made on A1N thin films sputtered on substrates with
      different conductivities. A discussion on the relation between the different
      circuital elements and the physical properties of the filters also is provided.

PMID- 18051172
TI  - Modeling and analysis on ring-type piezoelectric transformers.
AB  - This paper presents an electromechanical model for a ring-type piezoelectric
      transformer (PT). To establish this model, vibration characteristics of the
      piezoelectric ring with free boundary conditions are analyzed in advance. Based
      on the vibration analysis of the piezoelectric ring, the operating frequency and
      vibration mode of the PT are chosen. Then, electromechanical equations of motion
      for the PT are derived based on Hamilton's principle, which can be used to
      simulate the coupled electromechanical system for the transformer. Such as
      voltage stepup ratio, input impedance, output impedance, input power, output
      power, and efficiency are calculated by the equations. The optimal load
      resistance and the maximum efficiency for the PT will be presented in this paper.
      Experiments also were conducted to verify the theoretical analysis, and a good
      agreement was obtained.

PMID- 18051173
TI  - Calculation of dissipation resistances in a single-element transducer.
AB  - In this paper, a new formulation of the electrical input impedance of a single
      element transducer is presented. The resistive part of the electrical impedance
      that takes into account acoustic radiation in the front medium and losses in the
      transducer is split into a radiation resistance on one hand and into dissipation
      resistances related to each transducer component on the other hand. To confirm
      these theoretical results, characterization methods based on temperature
      measurements and pulse-echo response are presented. Measurements have been
      conducted on 1 MHz transducers, which consist of a piezoelectric ceramic glued on
      a backing. The results show a good agreement between experience and theory for
      dissipation resistance and radiation resistance values, which confirms the
      theoretical approach.

PMID- 18051174
TI  - Effective shear modulus reconstruction obtained with approximate mean normal
      stress remaining unknown.
AB  - We previously reported Methods A and B for reconstructing tissue shear modulus
      and density using mean normal stress as an unknown. The use of Method A enables
      us to obtain such reconstructions with the mean normal stress remaining unknown
      by using an iterative method to solve algebraic equations. However, Method A
      results in a low convergence speed and a low reconstruction accuracy compared
      with Method B that enables a reconstruction of mean normal stress together. Thus,
      in this report, we describe a new, rapid and accurate method, Method C, that
      enables the reconstructions of shear modulus and density in real time with a
      higher accuracy than Method A. In Method A, no reference mean normal stress is
      used. In Method C, an arbitrary finite value is used as a quasireference mean
      normal stress at an arbitrary point (i.e., a quasireference point) or an
      arbitrary region (i.e., a quasireference region) in the region of interest on the
      basis of the fact that the gradient operator implemented on the mean normal
      stress becomes positive-definite. When a quasireference region can be realized,
      Method C enables such reconstructions with a high accuracy and a high convergence
      speed similar to Method B. The effectiveness of Method C was verified using
      simulated phantom deformation data. Method C must be used instead of Method A as
      a practical method, in combination with Method B.

PMID- 18051175
TI  - On real-time optimal FIR estimation of linear TIE models of local clocks.
AB  - In this paper, we present an optimal finite-impulse response (FIR) filter for the
      linear time-interval error (TIE) model of a local clock and compare its estimates
      to those obtained by the unbiased FIR filter via the global positioning system
      (GPS)-based sawtooth measurements. We show theoretically and verify
      experimentally that there is no reasonable necessity in using optimal filters for
      GPS-based estimation of the TIE of precision crystal, rubidium, and cesium
      clocks. For these clocks, the optimal FIR filter requiring four coefficients
      degenerates to a simple unbiased FIR filter requiring only one coefficient.

PMID- 18051176
TI  - An analysis of partially electroded, contoured, quartz resonators with beveled
      cylindrical edges.
AB  - We report the last set of data from a series of theoretical studies of contoured
      resonators with beveled cylindrical edges. What is new in this report is that the
      contoured region is only partially electroded. The equation for transversely
      varying thickness modes in doubly-rotated quartz resonators is used. Resonant
      frequency, mode shape, and motional capacitance are calculated.

PMID- 18051180
TI  - An adaptable connectionist text-retrieval system with relevance feedback.
AB  - This paper introduces a new connectionist network for certain domain-specific
      text-retrieval and search applications with expert end users. A new model
      reference adaptive system is proposed that involves three learning phases.
      Initial model-reference learning is first performed based upon an ensemble set of
      input-output of an initial reference model. Model-reference following is needed
      in dynamic environments where documents are added, deleted, or updated. Relevance
      feedback learning from multiple expert users then optimally maps the original
      query using either a score-based or a click-through selection process. The
      learning can be implemented, in regression or classification modes, using a three
      layer network. The first layer is an adaptable layer that performs mapping from
      query domain to document space. The second and third layers perform document-to
      term mapping, search/retrieval, and scoring tasks. The learning algorithms are
      thoroughly tested on a domain-specific text database that encompasses a wide
      range of Hewlett Packard (HP) products and for a large number of most commonly
      used single- and multiterm queries.

PMID- 18051181
TI  - Neural network approach to background modeling for video object segmentation.
AB  - This paper presents a novel background modeling and subtraction approach for
      video object segmentation. A neural network (NN) architecture is proposed to form
      an unsupervised Bayesian classifier for this application domain. The constructed
      classifier efficiently handles the segmentation in natural-scene sequences with
      complex background motion and changes in illumination. The weights of the
      proposed NN serve as a model of the background and are temporally updated to
      reflect the observed statistics of background. The segmentation performance of
      the proposed NN is qualitatively and quantitatively examined and compared to two
      extant probabilistic object segmentation algorithms, based on a previously
      published test pool containing diverse surveillance-related sequences. The
      proposed algorithm is parallelized on a subpixel level and designed to enable
      efficient hardware implementation.

PMID- 18051182
TI  - The Bayesian ARTMAP.
AB  - In this paper, we modify the fuzzy ARTMAP (FA) neural network (NN) using the
      Bayesian framework in order to improve its classification accuracy while
      simultaneously reduce its category proliferation. The proposed algorithm, called
      Bayesian ARTMAP (BA), preserves the FA advantages and also enhances its
      performance by the following: (1) representing a category using a
      multidimensional Gaussian distribution, (2) allowing a category to grow or
      shrink, (3) limiting a category hypervolume, (4) using Bayes' decision theory for
      learning and inference, and (5) employing the probabilistic association between
      every category and a class in order to predict the class. In addition, the BA
      estimates the class posterior probability and thereby enables the introduction of
      loss and classification according to the minimum expected loss. Based on these
      characteristics and using synthetic and 20 real-world databases, we show that the
      BA outperformes the FA, either trained for one epoch or until completion, with
      respect to classification accuracy, sensitivity to statistical overlapping,
      learning curves, expected loss, and category proliferation.

PMID- 18051184
TI  - Hierarchically clustered adaptive quantization CMAC and its learning convergence.
AB  - The cerebellar model articulation controller (CMAC) neural network (NN) is a well
      established computational model of the human cerebellum. Nevertheless, there are
      two major drawbacks associated with the uniform quantization scheme of the CMAC
      network. They are the following: (1) a constant output resolution associated with
      the entire input space and (2) the generalization-accuracy dilemma. Moreover, the
      size of the CMAC network is an exponential function of the number of inputs.
      Depending on the characteristics of the training data, only a small percentage of
      the entire set of CMAC memory cells is utilized. Therefore, the efficient
      utilization of the CMAC memory is a crucial issue. One approach is to quantize
      the input space nonuniformly. For existing nonuniformly quantized CMAC systems,
      there is a tradeoff between memory efficiency and computational complexity.
      Inspired by the underlying organizational mechanism of the human brain, this
      paper presents a novel CMAC architecture named hierarchically clustered adaptive
      quantization CMAC (HCAQ-CMAC). HCAQ-CMAC employs hierarchical clustering for the
      nonuniform quantization of the input space to identify significant input segments
      and subsequently allocating more memory cells to these regions. The stability of
      the HCAQ-CMAC network is theoretically guaranteed by the proof of its learning
      convergence. The performance of the proposed network is subsequently benchmarked
      against the original CMAC network, as well as two other existing CMAC variants on
      two real-life applications, namely, automated control of car maneuver and
      modeling of the human blood glucose dynamics. The experimental results have
      demonstrated that the HCAQ-CMAC network offers an efficient memory allocation
      scheme and improves the generalization and accuracy of the network output to
      achieve better or comparable performances with smaller memory usages. Index Terms
      Cerebellar model articulation controller (CMAC), hierarchical clustering,
      hierarchically clustered adaptive quantization CMAC (HCAQ-CMAC), learning
      convergence, nonuniform quantization.

PMID- 18051185
TI  - Density-driven generalized regression neural networks (DD-GRNN) for function
      approximation.
AB  - This paper proposes a new nonparametric regression method, based on the
      combination of generalized regression neural networks (GRNNs), density-dependent
      multiple kernel bandwidths, and regularization. The presented model is generic
      and substitutes the very large number of bandwidths with a much smaller number of
      trainable weights that control the regression model. It depends on sets of
      extracted data density features which reflect the density properties and
      distribution irregularities of the training data sets. We provide an efficient
      initialization scheme and a second-order algorithm to train the model, as well as
      an overfitting control mechanism based on Bayesian regularization. Numerical
      results show that the proposed network manages to reduce significantly the
      computational demands of having individual bandwidths, while at the same time,
      provides competitive function approximation accuracy in relation to existing
      methods.

PMID- 18051190
TI  - Block-based neural networks for personalized ECG signal classification.
AB  - This paper presents evolvable block-based neural networks (BbNNs) for
      personalized ECG heartbeat pattern classification. A BbNN consists of a 2-D array
      of modular component NNs with flexible structures and internal configurations
      that can be implemented using reconfigurable digital hardware such as field
      programmable gate arrays (FPGAs). Signal flow between the blocks determines the
      internal configuration of a block as well as the overall structure of the BbNN.
      Network structure and the weights are optimized using local gradient-based search
      and evolutionary operators with the rates changing adaptively according to their
      effectiveness in the previous evolution period. Such adaptive operator rate
      update scheme ensures higher fitness on average compared to predetermined fixed
      operator rates. The Hermite transform coefficients and the time interval between
      two neighboring R-peaks of ECG signals are used as inputs to the BbNN. A BbNN
      optimized with the proposed evolutionary algorithm (EA) makes a personalized
      heartbeat pattern classifier that copes with changing operating environments
      caused by individual difference and time-varying characteristics of ECG signals.
      Simulation results using the Massachusetts Institute of Technology/Beth Israel
      Hospital (MIT-BIH) arrhythmia database demonstrate high average detection
      accuracies of ventricular ectopic beats (98.1%) and supraventricular ectopic
      beats (96.6%) patterns for heartbeat monitoring, being a significant improvement
      over previously reported electrocardiogram (ECG) classification results.

PMID- 18051193
TI  - A biologically inspired spiking neural network for sound source lateralization.
AB  - In this paper, a binaural sound source lateralization spiking neural network (NN)
      will be presented which is inspired by most recent neurophysiological studies on
      the role of certain nuclei in the superior olivary complex (SOC) and the inferior
      colliculus (IC). The binaural sound source lateralization neural network
      (BiSoLaNN) is a spiking NN based on neural mechanisms, utilizing complex neural
      models, and attempting to simulate certain parts of nuclei of the auditory system
      in detail. The BiSoLaNN utilizes both excitatory and inhibitory ipsilateral and
      contralateral influences arrayed in only one delay line originating in the
      contralateral side to achieve a sharp azimuthal localization. It will be shown
      that the proposed model can be used both for purposes of understanding the
      mechanisms of an NN of the auditory system and for sound source lateralization
      tasks in technical applications, e.g., its use with the Darmstadt robotic head
      (DRH).

PMID- 18051205
TI  - Carex (genus in family Cyperaceae).

PMID- 18051195
TI  - Synchrony in silicon: the gamma rhythm.
AB  - In this paper, we present a network of silicon interneurons that synchronize in
      the gamma frequency range (20-80 Hz). The gamma rhythm strongly influences
      neuronal spike timing within many brain regions, potentially playing a crucial
      role in computation. Yet it has largely been ignored in neuromorphic systems,
      which use mixed analog and digital circuits to model neurobiology in silicon. Our
      neurons synchronize by using shunting inhibition (conductance based) with a
      synaptic rise time. Synaptic rise time promotes synchrony by delaying the effect
      of inhibition, providing an opportune period for interneurons to spike together.
      Shunting inhibition, through its voltage dependence, inhibits interneurons that
      spike out of phase more strongly (delaying the spike further), pushing them into
      phase (in the next cycle). We characterize the interneuron, which consists of
      soma (cell body) and synapse circuits, fabricated in a 0.25-microm complementary
      metal-oxide-semiconductor (CMOS). Further, we show that synchronized interneurons
      (population of 256) spike with a period that is proportional to the synaptic rise
      time. We use these interneurons to entrain model excitatory principal neurons and
      to implement a form of object binding.

PMID- 18051206
TI  - A novel and effective approach to treating rhinitis with nasal antihistamines.
AB  - OBJECTIVES: To review existing treatments for rhinitis and summarize data
      available on the use of a nasal antihistamine (azelastine) in treating allergic
      and nonallergic vasomotor rhinitis. DATA SOURCES: Relevant articles and
      references published between 1995 and 2007 regarding the treatment of allergic
      and vasomotor rhinitis were identified from PubMed, review articles, meta
      analyses, and practice guidelines. STUDY SELECTION: All key relevant articles
      were reviewed and the most relevant selected for inclusion in this review.
      RESULTS: The efficacy and safety of azelastine nasal spray in treating allergic
      rhinitis and vasomotor rhinitis have been determined in a number of U.S.
      multicenter, randomized, double-blind, placebo-controlled trials. In all trials,
      azelastine was associated with a rapid onset of action and a sustained
      improvement over time in rhinitis, congestion, and other symptoms. In patients
      with allergic rhinitis, the combination of azelastine and nasal corticosteroids
      increased treatment efficacy by more than 40% compared with either product alone.
      CONCLUSIONS: Intranasal antihistamine therapy represents an effective mode of
      drug delivery in patients with allergic and nonallergic vasomotor rhinitis and is
      an important option for rhinitis therapy, particularly if rapid symptom relief is
      required or if congestion is a major symptom. Use of azelastine plus nasal
      corticosteroids is effective in both allergic rhinitis and vasomotor rhinitis,
      suggesting that this combination represents an effective treatment strategy for
      all patients with either allergic or nonallergic vasomotor rhinitis.

PMID- 18051207
TI  - Intimate behavior and allergy: a narrative review.
AB  - OBJECTIVE: To determine how sex and intimate contacts can represent a risk factor
      for allergic reactions, because they may favor direct contact with sensitizing
      substances. DATA SOURCES: We collected in this review the available literature on
      this subject. The MEDLINE database was searched by a combination of keywords: sex
      OR sexual intercourse OR kiss OR seminal plasma OR condom AND allergy OR allergic
      reaction. STUDY SELECTION: The studies retrieved were independently evaluated by
      the authors and included in this review based on their clinical pertinence (i.e.,
      dealing with clinical presentation, diagnosis, or treatment). RESULTS: Sex and
      intimate behavior seem to be increasingly described as triggers of allergic
      reactions, although the pertaining literature is represented mostly by case
      reports. Kissing has been described as a risk factor for food- and drug-induced
      severe reactions. Seminal plasma allergy has been repeatedly described and
      investigated. In this case, practical diagnostic algorithms have been proposed,
      and desensitization protocols are available. Similarly, there are numerous case
      reports of allergic reaction due to latex condoms, for which the diagnostic
      procedure is standardized. CONCLUSIONS: The available literature on intimate
      behavior, and sex in general, as a trigger of allergic reactions is not abundant.
      This is probably because of the particular nature of the problem, which concerns
      intimacy. Nevertheless, reliable diagnostic procedures are available in some
      specific cases. The possible link between sex and allergy should become part of
      the personal culture of allergists to extend and improve the diagnosis of unusual
      or unexplained conditions.

PMID- 18051208
TI  - The role of nasal allergy in chronic secretory otitis media.
AB  - BACKGROUND: Chronic secretory otitis media (SOM) has multifactorial causes, and
      nasal allergy is suspected as one of these causative factors. OBJECTIVES: To
      investigate the possible role of nasal allergy in SOM in adults and to determine
      the diagnostic value of nasal challenges with allergens (nasal provocation tests)
      combined with tympanometry for the diagnosis of this disorder. METHODS: In 69
      young adults with chronic or recurrent SOM, 173 nasal challenges with allergens
      were performed by anterior rhinomanometry combined with tympanometry (pure-tone
      air conduction tympanometry). In 42 control subjects with only allergic rhinitis
      and no history of middle ear disease, 42 nasal challenges with allergens were
      repeated and combined with tympanometry. The study design was a placebo
      controlled comparison. RESULTS: Of the 69 patients, 54 developed 129 positive
      nasal responses of various types (P < .01), 117 of which were accompanied by
      significant changes in middle ear pressure (P < .01). No significant
      tympanometric changes (P > .10) were recorded during the 42 positive nasal
      responses in control subjects. CONCLUSIONS: These results may confirm the
      occurrence of chronic SOM in some adult patients and the possible involvement of
      nasal allergy in chronic SOM. The nasal challenges with allergen performed by
      rhinomanometry, combined with tympanometry, seem to be a valuable supplementary
      tool for the diagnosis of this disorder.

PMID- 18051209
TI  - Risk factors related to fixed airway obstruction in patients with asthma after
      antiasthma treatment.
AB  - BACKGROUND: There are many unanswered questions about the role of airway
      remodeling in asthma. OBJECTIVE: To evaluate the physiologic factors related to
      airway remodeling after antiasthma drug treatment for 1 year. METHODS: We gave
      582 patients with asthma long-term control medication for 1 year according to the
      severity of their asthma. Airway remodeling was defined using forced expiratory
      volume in 1 second/forced vital capacity and a predicted forced expiratory volume
      in 1 second of less than 75% after antiasthma treatment. RESULTS: Of the 582
      patients, 49 (8.4%) had airway remodeling. Severe asthma resulted in more airway
      remodeling than mild-to-moderate asthma. Asthmatic patients with airway
      remodeling were significantly older and had a longer duration of asthma.
      Asthmatic patients with airway remodeling had more emphysema on high-resolution
      computed tomography, a higher rate of near-fatal asthma attacks, a lower
      percentage of sputum eosinophils, a lower atopy frequency, a greater response to
      short-acting bronchodilators, and a lower body mass index (BMI) than those
      without airway remodeling. Age, asthma duration, and BMI were important
      discriminators of airway remodeling. CONCLUSION: Nonatopy, asthma duration,
      emphysema on high-resolution computed tomography, sputum eosinophils, age, and
      BMI before antiasthma treatment are important factors related to airway
      remodeling in patients with asthma.

PMID- 18051210
TI  - Acute primary Chlamydophila pneumoniae bronchitis and bronchial
      hyperresponsiveness in young nonasthmatic Thai military recruits.
AB  - BACKGROUND: A correlation between chronic Chlamydophila pneumoniae infection and
      chronic airway diseases has been suggested by several studies, but direct
      evidence to support the link between acute Cpneumoniae infection and new-onset
      asthma is insufficient. OBJECTIVES: To determine the association between C.
      pneumoniae infection and subsequent bronchial hyperresponsiveness (BHR) and hence
      asthma. METHODS: We studied 110 Thai military conscripts during an epidemic of
      Cpneumoniae infection in Thailand, from November 1, 1998, through February 28,
      1999. The diagnosis was based on a standardized microimmunofluorescence
      technique. Spirometry and methacholine challenge tests (MCTs) were conducted.
      This cohort study excluded all conscripts with preexisting positive MCTs.
      RESULTS: Ninety-three percent of the conscripts presented with an acute cough of
      a mean duration of 15.2 days. The pattern of serologic response revealed that 83%
      had acute primary infections and 10% had acute reinfections. Mean forced
      expiratory volume in 1 second was 99.5%, with an improvement of 1.8% after
      bronchodilator administration. Only 3.6% revealed small airways disease (forced
      expiratory flow between 25% and 75% of <65%) on spirometry. Methacholine
      challenge tests failed to demonstrate BHR in all conscripts, and none had
      developed a new-onset wheeze (physician-diagnosed asthma) at up to 2 years of
      follow-up. CONCLUSIONS: This study demonstrates that cough in patients with acute
      primary Cpneumoniae infection is not associated with BHR among previously healthy
      adults. The pathogenetic mechanism by which organisms cause coughing and wheezing
      in acute bronchitis seems to be different among causative respiratory pathogens.

PMID- 18051211
TI  - A profile of U.S. asthma centers, 2006.
AB  - BACKGROUND: Asthma is a significant public health problem that results in 1.8
      million annual emergency department (ED) visits. Many ED visits may be prevented
      with specialized asthma care. OBJECTIVE: To describe US asthma centers with a
      long-term goal of exploring their potential role in improving outcomes for ED
      patients with acute asthma. METHODS: We conducted initial online surveys in 2004.
      One survey identified asthma centers and their directors through reports by
      emergency medicine researchers and fellowship directors (allergy/immunology,
      pulmonary, and critical care) at US hospitals. A second survey asked asthma
      center directors to describe their asthma center. Follow-up surveys were
      conducted 2 years later in 2006. RESULTS: Eighty-seven (49%) of the 177 hospitals
      surveyed have asthma clinics. Although spirometry was available on the day of the
      visit at all asthma centers surveyed in 2006, only 21% (95% confidence interval,
      11 %-34%) of sites reported that at least 90% of visits per week included a
      spirometry test. Only one quarter (26%; 95% confidence interval, 15%-40%) of
      asthma centers reported that at least 90% of patients undergo a skin or blood
      test for environmental allergens during 1 of their visits. Half of center
      directors (53%) were unsure of the approximate number of annual ED visits for
      acute asthma at their hospital. No significant measured changes were noted in
      asthma centers between 2004 and 2006. CONCLUSIONS: Asthma centers are
      heterogenous, with different services available. Although challenges remain,
      collaboration between EDs and asthma centers may contribute to improved asthma
      outcomes and merits further study.

PMID- 18051212
TI  - An economic evaluation of prophylactic self-injectable epinephrine to prevent
      fatalities in children with mild venom anaphylaxis.
AB  - BACKGROUND: Mild (cutaneous) venom anaphylaxis is the most common presentation of
      systemic venom hypersensitivity during childhood. Guidelines recommend
      prophylactic self-injectable epinephrine for children with mild venom
      anaphylaxis. However, progressive venom-associated reactions are uncommon in this
      population. OBJECTIVE: To characterize the cost-effectiveness of prophylactic
      self-injectable epinephrine in mild childhood venom anaphylaxis from a societal
      perspective. METHODS: Cohort simulations were used, and the base case was
      represented by a 6-year-old child with a history of mild venom-associated
      anaphylaxis. Long-term survival was modeled using age-adjusted mortality from the
      2002 U.S. life tables together with the risk of venom-associated mortality. Model
      assumptions included market costs of self-injectable epinephrine; the prevalence
      of venom allergy; US census estimates; venom-associated fatality estimates by the
      Joint Council of Allergy, Asthma, and Immunology (at least 40 deaths per year);
      and venom-associated mortality statistics from January 1, 1999, to December 31,
      2003, provided by the Centers for Disease Control and Prevention. RESULTS: The
      incremental cost of prophylactic self-injectable epinephrine for mild childhood
      venom anaphylaxis was $469,459 per year of life saved ($6,882,470 per death
      prevented). In sensitivity analyses, the strategy was only cost-effective when
      the annual venom-associated fatality rate exceeded 2 per 100,000 persons at risk.
      CONCLUSION: Use of prophylactic self-injectable epinephrine to prevent fatalities
      in children with mild venom anaphylaxis is not cost-effective if the annual venom
      associated fatality rate is less than 2 per 100,000 persons at risk.

PMID- 18051213
TI  - Food-induced anaphylaxis and repeated epinephrine treatments.
AB  - BACKGROUND: Research on the use of more than 1 dose of epinephrine in the
      treatment of food-induced anaphylaxis is limited. OBJECTIVE: To perform a medical
      record review to examine the frequency of repeated epinephrine treatments in
      patients presenting with food-induced anaphylaxis to the emergency department
      (ED). METHODS: We reviewed 39 medical records of patients who presented with food
      induced allergic reactions to the Massachusetts General Hospital ED during a 1
      year period. The analysis focused on the timing of the onset of symptoms and on
      the number of epinephrine treatments given before and during the ED visit.
      RESULTS: Of the 39 patients, 34 had an acute food-induced allergic reaction.
      Nineteen had anaphylaxis. Twelve patients with anaphylaxis (63%; 95% confidence
      interval, 38%-84%) received at least 1 dose of epinephrine, and 3 (16%; 95%
      confidence interval, 3%-40%) were given 2 doses. Although statistical analysis
      was not possible, repeated epinephrine treatment occurred in patients with
      anaphylaxis to peanut or tree nut and hypotension. There was no apparent
      association between time from ingestion of the causative agent to epinephrine
      treatment(s). CONCLUSIONS: Of patients presenting to the ED with food-induced
      anaphylaxis, approximately 16% were treated with 2 doses of epinephrine. This
      study supports the recommendation that patients at risk for food-induced
      anaphylaxis carry 2 doses of epinephrine. Further study is needed to confirm
      these results and to expand them to patients who do not present to the ED because
      that group may have a lower frequency of epinephrine use.

PMID- 18051214
TI  - Analysis of genetic defects in patients with the common variable immunodeficiency
      phenotype in a single Taiwanese tertiary care hospital.
AB  - BACKGROUND: Seven known genetic defects, including Bruton tyrosine kinase (Btk),
      CD4OL, and signaling lymphocyte activation molecule-associated protein (SAP) (all
      X-linked) and inducible costimulator molecule (ICOS), transmembrane activator and
      calcium-modulator and cytophilin ligand interactor (TACI), B-cell-activating
      factor of the tumor necrosis family receptor (BAFFR), and CD19 (all autosomal
      recessive), were found in patients with the phenotype of common variable
      immunodeficiency (CVID). OBJECTIVE: To investigate these 7 candidate protein
      expressions and candidate gene sequences for comprehensive analysis of known
      genetic defects in patients with CVID. METHODS: These 7 candidate protein
      expressions were evaluated by flow cytometry or Western blot, and candidate genes
      were evaluated by direct sequencing. RESULTS: Of 9 CVID patients from a single
      Taiwanese tertiary care hospital, we identified 2 cousins with decreased Btk
      expression who had a mutated (Asp521Val) kinase domain of Btk (1694A>T in exon
      15) and 1 patient with decreased CD40L expression who had a mutated (Thr254Met)
      extracellular domain of CD40L (782T>C in exon 5). CONCLUSION: This comprehensive
      approach revealed that, in Taiwan, in some patients mild forms of X-linked
      agammaglobulinemia and hyper-IgM syndrome caused the CVID phenotype. No mutations
      of SAP, ICOS, TACI, BAFFR, and CD19 were identified in this study, although
      selection bias among the small study population and genetic variation may exist.

PMID- 18051215
TI  - Effect of sublingual administration with a native or denatured protein allergen
      and adjuvant CpG oligodeoxynucleotides or cholera toxin on systemic T(H)2 immune
      responses and mucosal immunity in mice.
AB  - BACKGROUND: Sublingual immunotherapy has been recently used for allergic
      diseases, but its mechanisms are still unclear. OBJECTIVE: To examine the effect
      of sublingual administration of a native or denatured allergen alone or plus
      adjuvant on systemic T(H)2 responses and mucosal immunity in mice. METHODS: Naive
      or sensitized BALB/c mice were sublingually vaccinated biweekly for 3 weeks with
      ovalbumin (OVA) or urea-denatured OVA (CM-OVA) only or plus adjuvant CpG
      oligodeoxynucleotides (CpG) or cholera toxin (CT). Two weeks later, their
      specific serum IgG, IgG1, IgG2a, IgE, and saliva secretory IgA (SIgA) antibody
      responses and the cytokine profiles of spleen and cervical lymph node cells were
      investigated. RESULTS: Specific SIgA antibody responses were induced by
      vaccination with CM-OVA plus CpG or CT. Whereas vaccination with CM-OVA and CpG
      enhanced T(H)1 responses but inhibited IgE production, vaccination with CT and CM
      OVA or OVA increased cervical lymph node cell production of interleukin (IL) 4,
      IL-5, and IL-6 and serum IgG1 antibody responses. In previously sensitized mice,
      sublingual vaccination with OVA or CM-OVA plus CT or CpG stimulated mucosal SIgA
      antibody responses, but did not enhance ongoing IgE antibody responses.
      CONCLUSIONS: Sublingual vaccination with OVA or CM-OVA plus adjuvant CT or CpG
      all can induce systemic and mucosal immunity, but CM-OVA plus CpG had the best
      prophylactic and therapeutic effects on IgE antibody production. It is likely
      that sublingual vaccines may have a role for the prophylaxis and immunotherapy of
      allergic reactions.

PMID- 18051216
TI  - Sublingual-swallow immunotherapy with standardized 3-grass pollen extract: a
      double-blind, placebo-controlled study.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) is accepted as a safe and effective
      route for the treatment of grass pollen allergy, but clarification of its
      clinical and biological efficacy requires more study. OBJECTIVE: To evaluate the
      efficacy, safety, and compliance of SLIT with a standardized 3-grass pollen
      extract in patients with grass pollen seasonal allergic rhinoconjunctivitis, with
      or without mild asthma. METHODS: This multicenter, randomized, double-blind study
      included 127 patients (aged 12-41 years; mean age, 24.9 years) with grass pollen
      seasonal allergic rhinoconjunctivitis, with or without mild asthma. They received
      either SLIT with a high-dose, standardized, 3-grass pollen extract or placebo for
      10 months before and during the grass pollen season. The efficacy evaluation
      compared weekly clinical scores (defined as the sum of the symptom score and
      rescue medication score) to measure rhinoconjunctivitis and asthma for the first
      8 weeks of the pollen season. We also evaluated safety and compliance and
      measured changes in anti-Dactylis specific IgG4 antibody levels. RESULTS: There
      was a trend in favor of the study group in the mean adjusted clinical score. The
      groups were not comparable on inclusion (P = .02): the SLIT group included more
      subjects with asthma and had a higher mean IgG4 serum level. Additional
      exploration according to subgroups with and without asthma found that among the
      patients without asthma, the SLIT group had a significantly better clinical score
      (P = .045). Anti-Dactylis specific IgG4 levels increased significantly in the
      SLIT group. CONCLUSION: SLIT with a standardized, high-dose, 3-grass pollen
      extract is safe and significantly improves the clinical score in patients with
      hay fever and without asthma during the pollen season.

PMID- 18051217
TI  - Assessment and clinical interpretation of polysaccharide antibody responses.
AB  - This second article in the miniseries Practical Aspects of Ambulatory Diagnosis
      and Management of Immunodeficiency Disorders' extends the discussion on
      evaluation of individuals with suspected humoral immunodeficiency by reviewing
      the logistics and interpretation of the patient's ability to produce antibodies
      to polysaccharide antigens, specifically pneumococcal surface polysaccharides.
      The response to these polysaccharides is important in the evaluation of patients
      with documented immune abnormalities and those individuals who have normal total
      immunoglobulin levels. Although profound immune deficiencies, such as X-linked
      agammaglobulinemia and severe combined immunodeficiency, are always associated
      with a defect in specific antibody production, some immune disorders may have
      variable responses, whereas others with persistent IgG or IgG subclass
      deficiencies may have normal or clearly abnormal antipolysaccharide antibodies.
      Measurement of the response to pneumococcal polysaccharides is preferred because
      of the availability of a pure polysaccharide vaccine for antigen challenge and
      standardized techniques to measure specific antibody responses.

PMID- 18051218
TI  - Hypersensitivity pneumonitis as a cause of airway-centered interstitial fibrosis.
AB  - BACKGROUND: Airway-centered interstitial fibrosis (ACIF) has been postulated to
      be related to environmental exposures. OBJECTIVE: To describe a patient with ACIF
      associated with hypersensitivity pneumonitis. METHODS: We evaluated a patient
      with a 2-year history of progressive dyspnea and exercise intolerance. We
      performed computed tomography, pulmonary function tests, and skin prick tests.
      RESULTS: The patient's computed tomogram suggested hypersensitivity pneumonitis.
      Pulmonary function testing demonstrated a restrictive pattern. Results of skin
      prick tests to chicken, goose, canary, and budgie were negative. However, serum
      precipitins were positive to serum from pigeon, goose, duck, and chicken
      feathers. The patient was diagnosed as having ACIF. CONCLUSION: We believe that
      ACIF may represent a final common pathway for lung injury due to environmental
      exposure.

PMID- 18051220
TI  - Carboplatin desensitization.

PMID- 18051219
TI  - Radiocontrast-induced anaphylaxis despite pretreatment and use of iso-osmolar
      contrast.

PMID- 18051221
TI  - Response to "Allergist report: America faces an allergy/asthma crisis".

PMID- 18051222
TI  - [Quality of care in diabetic patients receiving pharmacologic treatment].
AB  - Diabetes mellitus is a chronic disease with an increasing prevalence. Appropriate
      treatment of the disease and prevention of chronic complications reduce morbidity
      and mortality in a cost-effective manner. These actions should be measured
      through the use of validated indicators for quality of care. The goal of this
      study was to assess the quality of care in diabetic patients under pharmacologic
      treatment in a private university hospital. A retrospective study was conducted
      in adult patients who bought insulin or oral hypoglycemic agents during a 3 month
      period; demographic and clinical data were obtained for 12 consecutive months
      following the buying period. The study included 305 adult patients; most were
      males (60%), with type 2 diabetes (95%), and using oral hipoglycemic agents
      (86%). Control of blood pressure was registered in 80%, foot exam in 5%, eye exam
      in 27%, HbA1C blood level in 85%, complete lipid profile in 82%, microalbuminuria
      in 27% and creatinine clearance in 22% of patients, respectively. Mean values
      were HbA1C 7.1(+/- 1.6)%, and < or = 7% in 66%, LDL 113 (+/- 33.6) mg/dl and <100
      mg/dl in 30%, BP 136-79 mm Hg and < 130-80 mm Hg in 46% of patients,
      respectively. This study emphasizes the need for quality of care assessment
      through validated indicators and points out the aspects that should be improved
      within a health care system.

PMID- 18051223
TI  - [Association between hip fractures and risk factors for osteoporosis.
      Multivariate analysis].
AB  - In this observational, case-control study, 376 inpatients were evaluated in order
      to determine the association of risk factors (RF) and hip fracture; 151 patients
      had osteoporotic hip fracture (cases); the remaining were controls. Data were
      obtained from medical charts, and through a standardized questionnaire about RF.
      Mean age of the sample (+/- SD) was 80.6 +/- 8.1 years, without statistically
      significant difference between cases and controls; the female:male ratio was 3:1
      in both groups. Fractured women were older than men (82.5 +/- 8.1 vs. 79.7 +/-
      7.2 years, respectively; p < 0.01). Physical activity, intake of alcohol and
      tobacco, and sun exposure were low in all patients. Falls among cases happened
      predominantly at home (p < 0.001). Among female cases, time spent in household
      duties was a RF (p = 0.007), which was absent in males. In multivariate analysis,
      the following RF were significantly more frequent: Cognitive impairment (p =
      0.001), and previous falls (p < 0.0001); whereas the following protective factors
      were significantly different from controls: Calcium intake during youth (p <
      0.0001), current calcium intake (p < 0.0001), and mechanical aid for walking (p <
      0.0001). Evaluation of RF and protective factors may contribute to diminish the
      probability of hip fracture, through a modification of personal habits, and
      measures to prevent falls among elderly adults. Present information can help to
      develop local and national population-based strategies to diminish the burden of
      hip fractures for the health system.

PMID- 18051224
TI  - [Lung involvement in systemic sclerosis].
AB  - The objective of this study was to determine clinical predictors of interstitial
      lung disease in patients with systemic sclerosis (SSc) and pulmonary involvement
      as defined by presence of a decreased diffusing capacity for carbon monoxide
      (DLCO). Forty subjects with SSc were retrospectively evaluated. Patients were
      categorized according to their level of DLCO (< o > or = 80% of predicted).
      Sensitivity of dyspnea to detect a decreased DLCO was 46.6% and specificity 90%,
      whereas oxygen desaturation showed a sensitivity of 71.4% and a specificity of
      80%. Patients with decreased DLCO (n = 18) were not different in age (51.1 +/-
      13.5 vs. 53.5 +/- 9.3 y, p = 0.5182), sex (male 13.6%, p = 0.6088), prevalence of
      Raynaud (86.6% vs. 85%, p = 0.6272), sicca syndrome (6.2% vs. 10.5% p = 1.0000)
      diffuse cutaneous involvement (94.1% vs. 83.3%, p = 0.6026) or esophageal
      dilatation. The duration of symptoms since diagnosis was no different. Prevalence
      of pulmonary hypertension assessed by Doppler echocardiography or abnormal
      nailfold capillaroscopic findings were identical in both populations. Patients
      with low DLCO had a significatly higher prevalence of anti topoisomerase
      antibodies. (5/9 vs. 0/11, p = 0.0081) and restrictive lung disease. Patients
      with low DLCO showed a significantly higher prevalence of abnormal HRCT findings
      suggestive of ILD (82.3% vs. 5.8%, p < or = 0.0001). We conclude that a low DLCO
      is a frequent finding in SSc patients, strongly associated with HRCT signs of
      ILD. We have not found clinical factors predictive for a low DLCO.

PMID- 18051225
TI  - Is tumor necrosis factor-376A promoter polymorphism associated with
      susceptibility to multiple sclerosis?
AB  - A single nucleotide polymorphism (SNP) at position -376 of the tumor necrosis
      factor alpha gene (TNFA) has been associated with susceptibility to multiple
      sclerosis (MS) in Spain. However, no association was found in populations from
      the USA and The Netherlands. Here we investigate the association between the TNFA
      376A SNP and MS susceptibility in Argentinean patients with MS. The A/G genotype
      was found in 4.4% of patients (n=90) and in 4.8% of healthy individuals (n=84;
      p=0.92; odds ratio=0.93; confidence interval: 0.23-3.84). Thus, no significant
      differences in genotype and allele frequencies were found between healthy
      individuals and patients with MS in Argentina.

PMID- 18051226
TI  - Effect of hypercortisolism control on high blood pressure in Cushing's syndrome.
AB  - Many hypertensive patients affected by endogenous Cushing's syndrome (CS) persist
      with high blood pressure (HBP) despite good control of cortisol excess. We
      assessed the effect of preoperative ketoconazole administration and of definitive
      treatment of CS on arterial hypertension and analysed the factors involved in the
      persistence of hypertension. We assessed retrospectively 71 patients with CS and
      HBP (60 women, 11 men; 50 pituitary, 21 adrenal) successfully treated by surgery
      and/or radiotherapy; 19 of them received ketoconazole (KNZ) before surgery. After
      treatment, patients were divided into those with persistent high blood pressure
      (PHBP) and those with normal blood pressure (NBP). As possible predictive factors
      for PHBP we analysed age, duration and family history of HBP, pre-treatment 24
      hour urinary free cortisol (24h-UFC) and body mass index (BMI). HBP normalized in
      53 out of 71 patients (74.6%), regardless of the origin of Cushing's syndrome.
      PHBP patients were older (p=0.003), had longer duration (p=0.007) and higher
      systolic blood pressure before treatment (p=0.046) than NBP patients. Thirteen
      out of 19 patients (68.4%) treated with ketoconazole, normalized their
      hypertension and remained normotensive after successful surgery. Five patients
      became normotensive only after surgery. IN CONCLUSION: a) blood pressure levels
      normalized in most patients after remission of CS; b) ketoconazole was effective
      for the Control of HBP and seems to be a good indicator of post-surgical outcome,
      and c) higher age at presentation, longer duration of hypertension and higher
      systolic blood pressure figures before treatment negatively influence
      normalization of blood pressure after resolution of Cushing's syndrome.

PMID- 18051227
TI  - Dual renin-angiotensin system blockade plus oral methylprednisone for the
      treatment of proteinuria in IgA nephropathy.
AB  - Renin-angiotensin system inhibition is a widely accepted approach to initially
      deal with proteinuria in IgA nephropathy, while the role of immunosuppressants
      remains controversial in many instances. A prospective, uncontrolled, open-label
      trial was undertaken in patients with biopsy-proven IgA nephropathy with
      proteinuria > 0.5 g/day and normal renal function to assess the efficacy of a
      combination treatment of angiotensin converting enzyme inhibitors plus
      angiotensin receptor blockers enalapril valsartan coupled with methylprednisone
      to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included:
      Age 37.45 +/- 13.26 years (50% male); 7 patients (35%) were hypertensive;
      proteinuria 2.2 +/- 1.86 g/day; serum creatinine 1.07 +/- 0.29 mg/dl; mean follow
      up 60.10 +/- 31.47 months. IgA nephropathy was subclassified according to Haas
      criteria. Twelve patients (60%) were class II; seven (35%) were class III and one
      (5%) class V. All patients received dual renin-angiotensin system blockade as
      tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8
      weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was
      reached. Oral steroids were discontinued after 24 weeks (6 months) of therapy but
      renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy
      proteinuria decreased to 0.15 +/- 0.07 g/day (P < 0.001) while serum creatinine
      did not vary: 1.07 +/- 0.28 mg/dl (P = ns). After a mean follow-up of 42.36 +/-
      21.56 months urinary protein excretion (0.12 +/- 0.06 g/day) and renal function
      (serum creatinine 1.06 +/- 0.27 mg/dl) remained stable. No major side effects
      were reported during the study. Renin-angiotensin blockade plus oral steroids
      proved useful to significantly decrease proteinuria to < 0.5 g/day in patients
      with IgA nephropathy without changes in renal function.

PMID- 18051228
TI  - Erythrocyte membrane, plasma and atherosclerotic plaque lipid pattern in coronary
      heart disease.
AB  - The objective was to analyze the lipid composition of the atherosclerotic plaque
      (AP), plasma and erythrocyte membrane (EM) in patients with advanced coronary
      heart disease (CHD). AP were obtained through endarterectomy in 18 patients. Ten
      normolipemic healthy subjects were selected to obtain the normal lipid pattern
      profile. Total lipids of AP and EM were determined by HPTLC, and the fatty acid
      profile from AP, EM and plasma using TLC-FID. The relative amount of the lipid
      species analyzed in AP was in line with the data in the literature
      [phospholipids: 23.5 mol% +/- 3.5; total cholesterol 68.9 mol% +/- 7.9;
      triglyceride 7.6 mol% +/- 3.4]. Plasma and EM from CHD patients compared to
      controls, showed a decrease in polyunsaturated fatty acids and an increase in
      saturated fatty acids leading to a decrease in the unsaturation index (plasma:
      1.67 +/- 0.06 vs. 1.28 +/- 0.03, P < 0.05; EM: 2.28 +/- 0.04 vs. 1.25 +/- 0.010,
      P < 0.05) and an enhancement in the saturated/unsaturated ratio (plasma: 0.35 +/-
      0.02 vs. 0.52 +/- 0.02, P < 0.05; EM: 0.45 +/- 0.01 vs. 0.83 +/- 0.04, P < 0.05).
      These data are consistent with an essential fatty acid deficiency. Total
      cholesterol was increased in the CHD's EM (32.3 +/- 0.8 vs. 40.6 +/- 2.5, P <
      0.05) with a decrease in phospholipid percentage (67.7 +/- 0.7 vs. 59.4 +/- 2.6,
      P < 0.05) indicating an alteration in membrane fluidity. These findings suggest
      changes in EM lipids in CHD patients in spite of different pathological
      conditions such as age, smoking status and diabetes. The analysis of the lipid
      composition of EM could provide a useful tool to monitor the evolution of the
      CHD.

PMID- 18051229
TI  - [Behavior of Argentine lymphocytic choriomeningitis virus strains in rodents].
AB  - The activity of LCM virus was first reported in Argentina at the beginning of the
      seventies and only five strains have been isolated from rodents Mus domesticus
      and two from humans. The objective of this paper was to find differential
      biological characteristics of Argentine strains of LCM virus comparing them in
      relation to the historical strains WE and Armstrong. Regarding the results
      obtained in tissue culture, when L 929 cells were used, plaque forming units
      (PFU) were obtained with human and mouse strains, whilst on Vero cells only human
      strains developed PFU. Differentials characteristics of historical and Argentine
      strain's plates were not found, neither differences related to the strain's
      origin. Neither historical nor Argentine strains were lethal to new-born mice
      giving a persistent infection, that was demonstrated when we inoculated new-born
      mouse by intracranial route with different strains of LCM virus and virus was
      isolated from brains harvested at different days post inoculation. The only
      exception was Cba An 13065 strain that exhibited virulence in new-born mice, only
      with 0.026 PFU was obtained 1 DL50. All the strains resulted lethal to adult
      mice. The mouse strains were more virulent than human strains, being Cba An 13065
      the most virulent. These results demonstrate a different behavior in tissue
      culture between human and mouse strains and allow the identification of virulence
      markers by intracranial inoculation into new-born or adult mice.

PMID- 18051230
TI  - [RAC3 nuclear receptor co-activator has a protective role in the apoptosis
      induced by different stimuli].
AB  - RAC3 belongs to the family of p160 nuclear receptors coactivators and it is over
      expressed in several tumors. We have previously shown that RAC3 is a NF-kappaB
      coactivator. In this paper, we investigated the role of RAC3 in cell-sensitivity
      to apoptosis, using H2O2 in the human embryonic kidney cell line (HEK293), and
      tumor necrosis factor-related apoptosis inducing ligand (TRAIL) in a human
      chronic myeloid leukemia cell line (K562) naturally resistant to TRAIL. We
      observed that the tumoral K562 cells have high levels of RAC3 if compared with
      the non-tumoral HEK293 cells. The normal or transfected coactivator over
      expression inhibits apoptosis through a diminished caspase activity and AIF
      nuclear translocation, increased NF-kappaB, AKT and p38, and decreased ERK
      activities. In contrast, inhibition of RAC3 by siRNA induced sensitivity of K562
      to TRAIL-induced apoptosis. Such results suggest that over-expression of RAC3
      contributes to tumor development through molecular mechanisms that do not depend
      strictly on acetylation and/or steroid hormones, which control cell death. This
      could be a possible target for future tumor therapies.

PMID- 18051231
TI  - [Systemic inflammation and experimental cancer in a murine model].
AB  - The link between cancer and inflammation in an organ or tissue has firmly been
      established on the basis that cancer tends to occur at sites of chronic
      inflammation and that local inflammatory processes can accelerate the growth of
      preexisting tumors in both animals and human beings. In contrast, the
      relationship between cancer and systemic inflammation has been less studied. In
      this work, we demonstrated that the growth of the murine fibrosarcoma MC-C, was
      accompanied by manifestations of systemic inflammation, as demonstrated by an
      increase in both the number of circulating polymorphonuclear neutrophils (PMN)
      and the serum concentration of the proinflammatory cytokines interleukin-1beta
      (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and
      the acute phase proteins C reactive (CRP) and serum A amyloid (SAA). Two
      temporally separate peaks of systemic inflammation were detected during tumor
      development. The first was displayed during the first week after tumor
      inoculation. The second peak began around day 14 and its intensity was
      proportional to tumor size. In mice bearing a large MC-C tumor, a high number of
      circulating PMN and myeloid precursors were evident. Most of these cells
      exhibited activation evidenced by an increased reactive oxygen species generation
      and high expression of the Gr1+/Mac1+ markers. Inoculation of thioglycolate 
      which generates a transient systemic inflammation-accelerated the growth of MC-C
      tumor and reciprocally, inhibition of such systemic inflammation by using
      indomethacin, prevented that enhancing effect. This suggests that the systemic
      inflammation that the tumor generates on its own, could be part of its growth
      strategy.

PMID- 18051232
TI  - [Pheochromocytoma associated with von Recklinghausen neurofibromatosis].
AB  - A pheochromocytoma is an adrenal gland tumor that secretes epinephrine and
      norepinephrine hormones, and is responsible for regulating heart rate and blood
      pressure, among other functions. The condition can occur alone or in combination
      with other disorders, and genetic and environmental factors play a key role.
      Neurofibromatosis-1 (NF-1) an inherited "autosomal dominant" disorder is one of
      the most common genetic disorders, characterized by formation of neurofibromas
      (tumors involving nerve tissue) in the skin, subcutaneous tissue, cranial and
      spinal root nerves. NF1 generally is diagnosed by physical examination. There is
      no cure for NF1, but there are ways to treat some of its effects.
      Neurofibromatosis arterial hypertension caused by pheochromocytoma is extremely
      rare, less frecuent than 1% in childrens less than 10 years old, and young
      adults. We present a case of an extremely infrequent association between
      neurofibromatosis and a pheochromocytoma in a young woman with a newly diagnosed
      hypertension. We discuss the underlying pathophysiological mechanisms and
      clinical implications.

PMID- 18051233
TI  - [Frey syndrome secondary to submaxillectomy and botulinic treatment].
AB  - A case of Frey syndrome (FS) secondary to submaxillar gland exeresis is presented
      and the results of the treatment with botulinum toxin (BTX) type A. FS is a
      condition of sweating cheek and preauricular area during realtime as a sequel
      detected in about 20-60% of patients after parotidectomy. The clinical symptoms
      include swelling, flushing and hyperhidrosis. The treatment choice for this
      condition is intracutaneous injection of BTX type A which blocks acetylcholine
      release at the sweat glands. A 30-year-old man, with thyroid medullar carcinoma
      diagnosed in 2002 received 6 cicles of cisplatin plus doxorubicin previous to the
      thyroidectomy with anterolateral neck dissection. During surgery the left ramus
      marginalis mandibulae was damaged. Two years later the patient referred sweating
      in submaxillar region during meals. CT scan demonstrated the absence of left
      submaxillar gland. Minor's test disclosed the affected area and BTX type A was
      injected (2.5 U/cm2/17 points). A twenty-one-day control showed a 95% reduction
      of the affected skin area. Persistent efficacy was observed up to one year follow
      up time when he was reinjected. The FS, also known as "gustatory hyperhidrosis",
      was probably first reported by M. Duphenix in 1757. Lucja Frey considered its
      physiopathology as a disorder of both sympathetic and parasympathetic
      innervation. In our case the FS was caused by a misdirected regeneration of
      postganglionic parasympathetic nerve fibers that arrised from the nervus
      lingualis rami ganglionares of the nervus trigeminus. After nerve injury the
      colinergic parasympathetic fibers seek out colinergic receptors--sympathetic
      receptors of the skin--innervating sweat glands and small skin vessels. All
      previous cases were located at masseter region post-parotidectomy. We have not
      found any description of FS in the submaxillary region. The self-assessed
      efficacy of the treatment with a hyperhidrosis disease severity scale revealed a
      very satisfied patient at 20 months follow-up after being injected twice with BTX
      type A.

PMID- 18051234
TI  - [Emergency contraception with levonorgestrel].
AB  - Emergency contraception may avoid pregnancy after unprotected intercourse or when
      regular contraceptive measures fail. Levonorgestrel, a synthetic gestagen, is
      recommended for emergency contraception as a single 1.5-mg dose or,
      alternatively, two 0.75-mg doses taken 12 h apart. Its efficacy is moderate,
      preventing about 80% of pregnancies. Efficacy is higher the earlier after
      unprotected intercourse the drug is taken, but it may be administered up to 5
      days post-coitum. Tolerance is similar to, or better than, those of other oral
      emergency contraceptives. Adverse effects include nausea, vomiting, headache,
      breast tenderness and transient alteration of menstrual bleeding pattern. It is
      not known whether levonogestrel increases the risk of ectopic pregnancy when the
      treatment fails. Its use as an ongoing contraceptive method is discouraged. When
      given before the preovulatory LH peak, levonorgestrel blocks or delays ovulation.
      It may also affect sperm migration in the female reproductive tract and have an
      effect on fertilization. Although it has been often postulated, there is no
      evidence for an anti-implantatory effect. Acquaintance with the method is quite
      variable among different societies, but it remains underutilized even where it is
      well known. Advance provision of the drug has been proposed as a way to promote
      its use. In clinical trials, advance provision did not adversely modify sexual or
      regular contraceptive behavior, but it did not reduce pregnancy or abortion rate
      either. Therefore, emergency contraception with levonorgestrel should be regarded
      as a backup method which is not a substitute for the continued use of more
      effective contraceptive methods.

PMID- 18051236
TI  - [Court intervention in medical decisions and the generation of new conflicts].
AB  - In the last decades, medical decisions are increasingly submitted to the courts
      of law for a number of reasons, also in our country. The various causes and
      different issues involved in such proceedings require comments referred to the
      possibility of causing an additional conflict to that which the courts of law are
      in theory required to address. In that context, this paper explores the repeated
      cases in which, due to the lack of positive legislation on a given issue, or due
      to different interpretations of existing legislation, or for lack of
      understanding of scientific progress or medical facts, defensive medicine finds
      its way to the detriment of society as a whole. In many other cases, fearful
      inexplicable attitudes of the doctors involved result in a transfer of
      exclusively medical decisions to the courts of law. This attitude contributes to
      the dismantling of a profession such as medicine, which is already subject to the
      difficult context of a variety of health systems that fail to sufficiently comply
      with their obligation of taking care of a community that needs and supports them.

PMID- 18051235
TI  - [Regulatory T cells and their influence in kidney allograft survival].
AB  - The immune response elicited by an allogenic transplant usually leads to an
      effector response resulting in allograft rejection; however, some individuals
      maintain a long-term functioning transplant without signs of rejection
      (operational tolerance) even in the absence of immunosuppression. It has been
      suggested that the same mechanisms are responsible for tolerance to self-antigens
      and alloantigens. One of such mechanisms is immune regulation and several cell
      subsets with regulatory properties have been identified. Among them, the best
      characterized cell populations are the regulatory T cells (Treg). Although Treg
      in mice are CD4+CD25+, in humans the Treg phenotype is restricted to CD4 T cells
      with high expression of CD25 (CD25high) and Foxp3. Phenotypic and functional
      analysis of circulating regulatory or suppressor T cells in transplant patients
      may be useful for detection of operationally tolerant patients. Moreover, future
      in vitro manipulation of these cells with therapeutic purposes could lead to
      accomplish induction of in vivo tolerance in clinical transplantation. Herein, we
      review the experimental and clinical evidence for the role of regulatory cells in
      transplant biology.

PMID- 18051237
TI  - [Cells and transistors].

PMID- 18051238
TI  - [Lymphangioleiomyomatosis and translational medicine].

PMID- 18051239
TI  - [Generational transformation of biomedical investigation].

PMID- 18051240
TI  - [Intestinal histoplasmosis in an HIV positive patient].

PMID- 18051241
TI  - [Penicillin allergy: real or consequence of?].

PMID- 18051242
TI  - Medical and technical protocol for automatic navigation of a wireless device in
      the carotid artery of a living swine using a standard clinical MRI system.
AB  - A 1.5 mm magnetic sphere was navigated automatically inside the carotid artery of
      a living swine. The propulsion force, tracking and real-time capabilities of a
      Magnetic Resonance Imaging (MRI) system were integrated into a closed loop
      control platform. The sphere was released using an endovascular catheter
      approach. Specially developed software is responsible for the tracking,
      propulsion, event timing and closed loop position control in order to follow a 10
      roundtrips preplanned trajectory on a distance of 5 cm inside the right carotid
      artery of the animal. Experimental protocol linking the technical aspects of this
      in vivo assay is presented. In the context of this demonstration, many challenges
      which provide insights about concrete issues of future nanomedical interventions
      and interventional platforms have been identified and addressed.

PMID- 18051243
TI  - [The Hisayama study from the viewpoint of gerentology].

PMID- 18051244
TI  - [Tumor-suppressing role of cellular senescence and chromatin structure].

PMID- 18051245
TI  - Abstracts of the 9th International Workshop on Adverse Drug Reactions and
      Lipodystrophy in HIV, 19-21 July 2007, Sydney, Australia.

PMID- 18051246
TI  - Why theory matters.

PMID- 18051247
TI  - Bibliography. Current world literature. Gastrointestinal hormones.

PMID- 18051248
TI  - Bibliography. Current world literature. Neuroendocrinology.

PMID- 18051249
TI  - Bibliography. Current world literature. Thyroid.

PMID- 18051250
TI  - Abstracts of the 19th Annual Symposium of Transcatheter Cardiovascular
      Therapeutics, October 20-25, 2007, Washington, DC, USA.

PMID- 18051251
TI  - [News about restless legs syndrome].

PMID- 18051252
TI  - The corrected values for duration and frequency of angina at baseline in the
      clinical outcomes utilizing revascularization and aggressive drug evaluation
      trial.

PMID- 18051253
TI  - Bibliography. Current world literature. Reproductive endocrinology.

PMID- 18051254
TI  - [Yes to warning illustrations on tobacco products].

PMID- 18051255
TI  - [Debate about the indication for neurophysiologic examination in upper extremity
      pain].

PMID- 18051256
TI  - Bibliography. Current world literature. Raynaud phenomenon, scleroderma, overlap
      syndromes and other fibrosing syndromes.

PMID- 18051257
TI  - Bibliography. Current world literature. Infectious arthritis and immune
      dysfunction.

PMID- 18051258
TI  - [Future hospital services].

PMID- 18051259
TI  - "A more enlightened approach?" Venereal disease legislation in post World War II
      Australia.

PMID- 18051260
TI  - [Names as bodily signs: the example of Yemeni women of nobility].

PMID- 18051261
TI  - Madness and colonization: psychiatry in the British and French Empires, 1800
      1962.

PMID- 18051262
TI  - Urchins, loafers and the cult of the cowboy: urbanization and delinquency in Dar
      es Salaam, 1919-61.

PMID- 18051263
TI  - Hospital emergency on-call coverage: is there a doctor in the house?
AB  - The nation's community hospitals face increasing problems obtaining emergency on
      call coverage from specialist physicians, according to findings from the Center
      for Studying Health System Change's (HSC) 2007 site visits to 12 nationally
      representative metropolitan communities. The diminished willingness of specialist
      physicians to provide on-call coverage is occurring as hospital emergency
      departments confront an ever-increasing demand for services. Factors influencing
      physician reluctance to provide on-call coverage include decreased dependence on
      hospital admitting privileges as more services shift to non-hospital settings;
      payment for emergency care, especially for uninsured patients; and medical
      liability concerns. Hospital strategies to secure on-call coverage include
      enforcing hospital medical staff bylaws that require physicians to take call,
      contracting with physicians to provide coverage, paying physicians stipends, and
      employing physicians. Nonetheless, many hospitals continue to struggle with
      inadequate on-call coverage, which threatens patients' timely access to high
      quality emergency care and may raise health care costs.

PMID- 18051264
TI  - Bacillus thuringiensis as a specific, safe, and effective tool for insect pest
      control.
AB  - Bacillus thuringiensis (Bt) was first described by Berliner [10] when he isolated
      a Bacillus species from the Mediterranean flour moth, Anagasta kuehniella, and
      named it after the province Thuringia in Germany where the infected moth was
      found. Although this was the first description under the name B. thuringiensis,
      it was not the first isolation. In 1901, a Japanese biologist, Ishiwata
      Shigetane, discovered a previously undescribed bacterium as the causative agent
      of a disease afflicting silkworms. Bt was originally considered a risk for
      silkworm rearing but it has become the heart of microbial insect control. The
      earliest commercial production began in France in, 1938, under the name Sporeine
      [72]. A resurgence of interest in Bt has been attributed to Edward Steinhaus
      [105], who obtained a culture in 1942 and attracted attention to the potential of
      Bt through his subsequent studies. In 1956, T. Angus [3] demonstrated that the
      crystalline protein inclusions formed in the course of sporulation were
      responsible for the insecticidal action of Bt. By the early 1980's, Gonzalez et
      al. [48] revealed that the genes coding for crystal proteins were localized on
      transmissible plasmids, using a plasmid curing technique, and Schnepf and
      Whiteley [103] first cloned and characterized the genes coding for crystal
      proteins that had toxicity to larvae of the tobacco hornworm, from plasmid DNA of
      Bt subsp. kurstaki HD-1. This first cloning was followed quickly by the cloning
      of many other cry genes and eventually led to the development of Bt transgenic
      plants. In the 1980s, several scientists successively demonstrated that plants
      can be genetically engineered, and finally, Bt cotton reached the market in 1996
      [104].

PMID- 18051265
TI  - Microbial community profiling in cis- and trans-dichloroethene enrichment systems
      using denaturing gradient gel electrophoresis.
AB  - The effective and accurate assessment of the total microbial community diversity
      is one of the primary challenges in modem microbial ecology, especially for the
      detection and characterization of unculturable populations and populations with a
      low abundance. Accordingly, this study was undertaken to investigate the
      diversity of the microbial community during the biodegradation of cis- and trans
      dichloroethenes in soil and wastewater enrichment cultures. Community profiling
      using PCR targeting the 16S rRNA gene and denaturing gradient gel electrophoresis
      (PCR-DGGE) revealed an alteration in the bacterial community profiles with time.
      Exposure to cis- and trans-dichloroethenes led to the disappearance of certain
      genospecies that were initially observed in the untreated samples. A cluster
      analysis of the bacterial DGGE community profiles at various sampling times
      during the degradation process indicated that the community profile became stable
      after day 10 of the enrichment. DNA sequencing and phylogenetic analysis of
      selected DGGE bands revealed that the genera Acinetobacter, Pseudomonas,
      Bacillus, Comamonas, and Arthrobacter, plus several other important uncultured
      bacterial phylotypes, dominated the enrichment cultures. Thus, the identified
      dominant phylotypes may play an important role in the degradation of cis- and
      trans-dichloroethenes.

PMID- 18051266
TI  - Production and characterization of monoclonal and recombinant antibodies against
      antimicrobial sulfamethazine.
AB  - A monoclonal antibody (mab) against the antimicrobial sulfamethazine was prepared
      and characterized by an indirect competitive enzyme-linked immunosorbent assay
      (IC-ELISA). Sulfamethazine in the range of 0.2 and 45 ng/ml could be determined
      with the mab by IC-ELISA. cDNAs encoding a variable heavy chain and variable
      light chain of the mab were cloned to produce recombinant antibodies using phage
      display technology. Following phage rescue and three rounds of panning, a single
      chain variable fragment (scFv) antibody with high sulfamethazine-binding affinity
      was obtained. ELISA analysis revealed that scFv antibody and parent mab showed
      similar, but not identical, characteristics. The IC50 value by IC-ELISA with scFv
      antibody was 4.8 ng/ml, compared with 1.6 ng/ml with the parent mab. Performances
      of the assays in the presence of milk matrix were compared; the mab-based assay
      was less affected than the scFv-based assay. Sixty milk samples were analyzed by
      mab-based IC-ELISA, and four samples were sulfamethazine positive; these results
      were favorably correlated with those obtained by HPLC.

PMID- 18051267
TI  - Expression of recombinant human growth hormone in a soluble form in Escherichia
      coli by slowing down the protein synthesis rate.
AB  - Formation of inclusion bodies is usually observed when foreign proteins are
      overexpressed in E. coli. The formation of inclusion bodies might be prevented by
      lowering the rate of protein synthesis, and appropriate regulation of the protein
      expression rate may lead to the soluble expression. In this study, human growth
      hormone (rhGH) was expressed in a soluble form by slowing down the protein
      synthesis rate, which was controlled in the transcriptional and translational
      levels. The transcriptional level was controlled by the regulation of the amount
      of RNA polymerase specific to the promoter in front of the rhGH gene. For
      lowering the rate of translation, the T7 transcription terminator-deleted vector
      was used to synthesize the longer mRNA of the target gene because the longer mRNA
      is expected to reduce the availability of free ribosomes. In both methods, the
      percentage of soluble expression increased when the expression rate slowed down,
      and more than 93% of rhGH expressed was a soluble form in the T7 transcription
      terminator-deleted expression system.

PMID- 18051268
TI  - Inhibition of seed germination and induction of systemic disease resistance by
      Pseudomonas chlororaphis O6 requires phenazine production regulated by the global
      regulator, gacS.
AB  - Seed coating by a phenazine-producing bacterium, Pseudomonas chlororaphis O6,
      induced dose-dependent inhibition of germination in wheat and barley seeds, but
      did not inhibit germination of rice or cucumber seeds. In wheat seedlings grown
      from inoculated seeds, phenazine production levels near the seed were higher than
      in the roots. Deletion of the gacS gene reduced transcription from the genes
      required for phenazine synthesis, the regulatory phzI gene and the biosynthetic
      phzA gene. The inhibition of seed germination and the induction of systemic
      disease resistance against a bacterial soft-rot pathogen, Erwinia carotovora
      subsp. carotovora, were impaired in the gacS and phzA mutants of P chlororaphis
      O6. Culture filtrates of the gacS and phzA mutants of P chlororaphis 06 did not
      inhibit seed germination of wheat, whereas that of the wild-type was inhibitory.
      Our results showed that the production of phenazines by P chlororaphis O6 was
      correlated with reduced germination of barley and wheat seeds, and the level of
      systemic resistance in tobacco against E. carotovora.

PMID- 18051269
TI  - Abridged region from Escherichia coli periplasmic stress sensor DegS acts as
      plasminogen activator in vitro.
AB  - It is well known that the Escherichia coli inner membrane-bound protease DegS is
      a periplasmic stress sensor for unfolded outer membrane proteins (OMPs). Previous
      studies have also shown that the outer membrane protease OmpT activates
      plasminogen in vitro and this may be exploited by bacteria in the course of
      pathogenesis. However, there has been no research on the plasminogen activation
      ability of the important periplasmic protein DegS. Accordingly, in this study,
      the whole-length and truncated degS genes were separately overexpressed in
      Escherichia coli, the recombinant proteins purified by affinity chromatography,
      and their plasminogen activator role tested in vitro. The results suggested that
      the whole-length DegS was able to activate plasminogen on a plasma plate. The
      truncated form of DegS (residues 80-345), designated delta DegS, also acted as a
      plasminogen activator, as confirmed by different assays. The serine protease
      property of delta DegS was verified based on the complete inhibition of its
      enzyme activity by PMSF (phenylmethanesulfonyl fluoride). Therefore, the present
      results indicate that DegS is a plasminogen activator in vitro.

PMID- 18051270
TI  - Effect of ionic liquid on the kinetics of peroxidase catalysis.
AB  - The effect of a water-miscible ionic liquid, 1-butyl-3-methylimidazolium
      tetrafluoroborate ([BMIM][BF4]), on the horseradish peroxidase (HRP)-catalyzed
      oxidation of 2-methoxyphenol (guaiacol) with hydrogen peroxide (H2O2) was
      investigated. HRP maintains its high activity in the aqueous mixtures containing
      various concentrations of the ionic liquid and even in 90% (v/v) ionic liquid. In
      order to minimize the effect of solution viscosity on the kinetic constants of
      HRP catalysis, the enzymatic reactions in the subsequent kinetic study were
      performed in water-ionic liquid mixtures containing 25% (v/v) ionic liquid at
      maximum. As the concentration of [BMIM][BF4] increased for the oxidation of
      guaiacol by HRP, the K(m) value increased with a slight decrease in the k(cat)
      value: The K(m) value increased from 2.8 mM in 100% (v/v) water to 22.5 mM in 25%
      (v/v) ionic liquid, indicating that ionic liquid significantly weakens the
      binding affinity of guaiacol to HRP.

PMID- 18051271
TI  - Cloning, expression, and characterization of a cold-adapted lipase gene from an
      antarctic deep-sea psychrotrophic bacterium, Psychrobacter sp 7195.
AB  - A psychrotrophic strain 7195 showing extracellular lipolytic activity towards
      tributyrin was isolated from deep-sea sediment of Prydz Bay and identified as a
      Psychrobacter species. By screening a genomic DNA library of Psychrobacter sp.
      7195, an open reading frame of 954 bp coding for a lipase gene, lipA1, was
      identified, cloned, and sequenced. The deduced LipA1 consisted of 317 amino acids
      with a molecular mass of 35,210 kDa. It had one consensus motif, G-N-S-M-G
      (GXSXG), containing the putative active-site serine, which was conserved in other
      cold-adapted lipolytic enzymes. The recombinant LipA1 was purified by column
      chromatography with DEAE Sepharose CL-4B, and Sephadex G-75, and preparative
      polyacrylamide gel electrophoresis, in sequence. The purified enzyme showed
      highest activity at 30 degrees C, and was unstable at temperatures higher than 30
      degrees C, indicating that it was a typical cold-adapted enzyme. The optimal pH
      for activity was 9.0, and the enzyme was stable between pH 7.0-10.0 after 24 h
      incubation at 4 degrees C. The addition of Ca2+ and Mg2+ enhanced the enzyme
      activity of LipA1, whereas the Cd2, Zn2+, Co2+, Fe3+, Hg2+, Fe2+, Rb2+, and EDTA
      strongly inhibited the activity. The LipA1 was activated by various detergents,
      such as Triton X-100, Tween 80, Tween 40, Span 60, Span 40, CHAPS, and SDS, and
      showed better resistance towards them. Substrate specificity analysis showed that
      there was a preference for trimyristin and p-nitrophenyl myristate (C14 acyl
      groups).

PMID- 18051272
TI  - Immunogenicity and safety of Vi capsular polysaccharide typhoid vaccine in
      healthy persons in Korea.
AB  - The purpose of this study was to evaluate the immunogenicity and safety of
      Salmonella Typhi Vi capsular polysaccharide vaccine (Vi vaccine) in Korea. The
      immunogenicity of a single dose of Vi vaccine was evaluated in 157 subjects (75
      children and 82 adults) before and at 1, 6, and 12 months after vaccination.
      Immunogenicity was measured with a passive hemagglutination assay (PHA),
      quantified as geometric mean titers (GMTs) and seroconversion rates. The safety
      of the vaccine was investigated by determining adverse reactions occurring within
      4 h, 3 days, and 1 month after injection. The seroconversion rate for children
      and adults 1 month after vaccination was 96.92% and 89.02%, respectively. In the
      case of children, the GMTs of Vi antibodies before vaccination were 5.87 +/- 1.34
      and 142.59 +/- 2.39 at one month after vaccination. For adults, the GMTs before
      and one month after vaccination were 5.58 +/- 1.28 and 58.56 +/- 3.67,
      respectively. Vi antibodies persisted for as long as 6 and 12 months after
      vaccination. All adverse reactions in adults and children were minor and did not
      require treatment. The Vi CPS vaccine was safe and immunogenic in adults and
      children older than 5 years.

PMID- 18051273
TI  - Effects of inoculum level and pressure pulse on the inactivation of Clostridium
      sporogenes spores by pressure-assisted thermal processing.
AB  - The effects of initial concentration and pulsed pressurization on the
      inactivation of Clostridium sporogenes spores suspended in deionized water were
      determined during thermal processing (TP; 105 degrees C, 0.1 MPa) and pressure
      assisted thermal processing (PATP; 105 degrees C and 700 MPa) treatments for 40
      min and 5 min holding times, respectively. Different inoculum levels (10(4),
      10(6), and 10(8) CFU/ml) of C. sporogenes spores suspended in deionized water
      were treated at 105 degrees C under 700 MPa with single, double, and triple
      pulses. Thermally treated samples served as control. No statistical significances
      (p > 0.05) were observed among all different inoculum levels during the thermal
      treatment, whereas the inactivation rates (k1 and k2) were decreased with
      increasing the initial concentrations of C. sporogenes spores during the PATP
      treatments. Double- and triple-pulsed pressurization reduced more effectively the
      number of C. sporogenes spores than single-pulse pressurization. The study shows
      that the spore clumps formed during the PATP may lead to an increase in pressure
      thermal resistance, and multiple-pulsed pressurization can be more effective in
      inactivating bacterial spores. The results provide an interesting insight on the
      spore inactivation mechanisms with regard to inoculum level and pulsed
      pressurization.

PMID- 18051274
TI  - Purification and characterization of two thermostable proteases from the
      thermophilic fungus Chaetomium thermophilum.
AB  - Thermostable protease is very effective to improve the industrial processes in
      many fields. Two thermostable extracellular proteases from the culture
      supernatant of the thermophilic fungus Chaetomium thermophilum were purified to
      homogeneity by fractional ammonium sulfate precipitation, ion-exchange
      chromatography on DEAE-Sepharose, and PhenylSepharose hydrophobic interaction
      chromatography. By SDS-PAGE, the molecular mass of the two purified enzymes was
      estimated to be 33 kDa and 63 kDa, respectively. The two proteases were found to
      be inhibited by PMSF, but not by iodoacetamide and EDTA. The 33 kDa protease
      (PRO33) exhibited maximal activity at pH 10.0 and the 63 kDa protease (PRO63) at
      pH 5.0. The optimum temperature for the two proteases was 65 degrees C. The PRO33
      had a K(m) value of 6.6 mM and a V(max) value of 10.31 micromol/l/min, and PRO63
      17.6 mM and 9.08 micromol/l/min, with casein as substrate. They were thermostable
      at 60 degrees C. The protease activity of PRO33 and PRO63 remained at 67.2% and
      17.31%, respectively, after incubation at 70 degrees C for 1 h. The thermal
      stability of the two enzymes was significantly enhanced by Ca2+. The residual
      activity of PRO33 and PRO63 at 70 degrees C after 60 min was approximately 88.59%
      and 39.2%, respectively, when kept in the buffer containing Ca2+. These
      properties make them applicable for many biotechnological purposes.

PMID- 18051275
TI  - A cytoplasmic polyhedrosis virus isolated from the pine processionary
      caterpillar, Thaumetopoea pityocampa.
AB  - A cytoplasmic polyhedrosis virus (CPV) was isolated from the larvae of
      Thaumetopoea pityocampa and shown to cause an infection of midgut cells. This
      viral infection revealed several important diagnostic symptoms, including
      discoloration of the posterior midgut, reduced feeding, and extended development
      time of the larvae. The virus infection is lethal to Thaumetopoea pityocampa, and
      with the increasing doses kills the larvae within 4-5 days post infection.
      Electron microscopy studies showed typical cytoplasmic polyhedral inclusion
      bodies that are icosahedral, and ranged from 2.4 to 5.3 microm in diameter.
      Electrophoretic analysis of the RNA genome showed that the virus has a genome
      composed of 10 equimolar RNA segments with the sizes of 3,907, 3,716, 3,628,
      3,249, 2,726, 1,914, 1,815, 1,256, 1,058, and 899 bp, respectively. Based on
      morphology and nucleic acid analysis, this virus was named Thaumetopoea
      pityocampa cytoplasmic polyhedrosis virus (TpCPV), and belongs to the genus
      Cypovirus, family Reoviridae.

PMID- 18051276
TI  - Stress-governed expression and purification of human type II hexokinase in
      Escherichia coli.
AB  - The full encoding sequence for human type II hexokinase (HXK II) was cloned into
      the E. coli expression vector pET 21b and expressed as a C-terminally
      hexahistidine-tagged protein in the BL21 (DE3) strain. The IPTG-induced HXK II
      approximately accounted for 17% of the total E. coli proteins, and 81% of HXK
      II(6xHis) existed in inclusion bodies. To improve the production of soluble
      recombinant HXK II protein, in the functionally active form, we used low
      temperature, and the osmotic stress expression method. When expressed at 18
      degrees C, about 83% of HXK II(6xHis) existed in the soluble fraction, which
      amounted to a 4.1-fold yield over that expressed at 37 degrees C. The soluble
      form of HXK II(6xHis) was also highly produced in the presence of 1 M sorbitol
      under the standard condition (37 degrees C), which indicated that temperature
      downshift and low water potentials were required to improve the yield of active
      recombinant HXK II protein. The expressed protein was purified by metal chelate
      affinity chromatography performed in an IDA Excellose column charged with Ni2+
      ions, resulting in about 40 mg recombinant HXK II protein obtained with purity
      over 89% from 5 l of E. coli culture. The identity of HXK II(6xHis) was confirmed
      by Western blotting analysis. Taken together, using the stress-governed
      expression described in this study, human active HXK II can be purified in
      sufficient amounts for biochemical and biomedical studies.

PMID- 18051277
TI  - A response surface model based on absorbance data for the growth rates of
      Salmonella enterica serovar typhimurium as a function of temperature, NaCl, and
      pH.
AB  - Response surface model was developed for predicting the growth rates of
      Salmonella enterica sv. Typhimurium in tryptic soy broth (TSB) medium as a
      function of combined effects of temperature, pH, and NaCl. The TSB containing six
      different concentrations of NaCl (0, 2, 4, 6, 8, and 10%) was adjusted to an
      initial of six different pH levels (pH 4, 5, 6, 7, 8, 9, and 10) and incubated at
      10 or 20 degrees C. In all experimental variables, the primary growth curves were
      well (r2 = 0.900 to 0.996) fitted to a Gompertz equation to obtain growth rates.
      The secondary response surface model for natural logarithm transformations of
      growth rates as a function of combined effects of temperature, pH, and NaCl was
      obtained by SAS's general linear analysis. The predicted growth rates of the S.
      Typhimurium were generally decreased by basic (9, 10) or acidic (5, 6) pH levels
      or increase of NaCl concentrations (0-8%). Response surface model was identified
      as an appropriate secondary model for growth rates on the basis of coefficient
      determination (r2 = 0.960), mean square error (MSE = 0.022), bias factor (B(f) =
      1.023), and accuracy factor (A(f) = 1.164). Therefore, the developed secondary
      model proved reliable predictions of the combined effect of temperature, NaCl,
      and pH on growth rates for S. Typhimurium in TSB medium.

PMID- 18051278
TI  - Optimization of lipase pretreatment prior to lipase immobilization to prevent
      loss of activity.
AB  - In our previous work, a method of pretreating lipase was developed to prevent
      loss of its activity during covalent immobilization. In this study, Rhizopus
      oryzae lipase was pretreated before immobilization and then immobilized on a
      silica gel surface. The effects of the various materials and conditions used in
      the pretreatment stage on the activity of immobilized lipase were investigated.
      Immobilized lipase pretreated with 0.1% of soybean oil had better activity than
      those pretreated with other materials. The optimal temperature, agitation speed,
      and pretreating time for lipase pretreatment were determined to be 40 degrees C,
      200 rpm, and 45 min, respectively. The activity of immobilized soybean oil
      pretreated lipase was 630 U/g matrix, which is 20 times higher than that of
      immobilized non-pretreated lipase. In addition, immobilized lipase activity was
      maintained at levels exceeding 90% of its original activity after 10 reuses.

PMID- 18051279
TI  - Effect of dietary inclusion of Lactobacillus acidophilus ATCC 43121 on
      cholesterol metabolism in rats.
AB  - This study examined the effects of Lactobacillus acidophilus ATCC 43121 (LAB) on
      cholesterol metabolism in hypercholesterolemia-induced rats. Four treatment
      groups of rats (n = 9) were fed experimental diets: normal diet, normal diet+LAB
      (2 x 10(6) CFU/day), hypercholesterol diet (0.5% cholesterol, w/w), and
      hypercholesterol diet + LAB. Body weight, feed intake, and feed efficiency did
      not differ among the four groups. Supplementation with LAB reduced total serum
      cholesterol (25%) and VLDL + IDL + LDL cholesterol (42%) in hypercholesterol diet
      groups, although hepatic tissue cholesterol and lipid contents were not changed.
      In the normal diet group, cholesterol synthesis (HMG-CoA reductase expression),
      absorption (LDL receptor expression), and excretion via bile acids (cholesterol 7
      alpha-hydroxylase expression) were increased by supplementation with LAB, and
      increased cholesterol absorption and decreased excretion were found in the
      hypercholesterol diet group. Total fecal acid sterols excretion was increased by
      supplementation with LAB. With proportional changes in both normal and
      hypercholesterol diet groups, primary bile acids (cholic and chenodeoxycholic
      acids) were reduced, and secondary bile acids (deoxycholic and lithocholic acids)
      were increased. Fecal neutral sterol excretion was not changed by LAB. In this
      experiment, the increase in insoluble bile acid (lithocholic acid) reduced blood
      cholesterol level in rats fed hypercholesterol diets supplemented with LAB. Thus,
      in the rat, L. acidophilus ATCC 43121 is more likely to affect deconjugation and
      dehydroxylation during cholesterol metabolism than the assimilation of
      cholesterol into cell membranes.

PMID- 18051280
TI  - Morphological changes induced in listeria monocytogenes V7 by a bacteriocin
      produced by Pediococcus acidilactici.
AB  - Pediococcus acidilactici produces bacteriocin, which kills Listeria
      monocytogenes. The bactericidal mode of action of the bacteriocin against L.
      monocytogenes V7 was investigated by transmission electron microscopy. The
      bacteriocin was purified partially from the cell-free extract using Micro-Cel and
      cation-exchange chromatography, and the specific activity was increased 1,791
      fold. The bacteriocin (6,400 AU/ ml) was inoculated with L. monocytogenes V7 and
      incubated for 0.5 h, 1 h, 3 h, and 6 h. The bacteriocin was found to destroy most
      of the cell wall and released most of the inclusions in the cells after 6 h of
      incubation. These results suggest that the bactericidal effect of the bacteriocin
      was due to bacterial lysis.

PMID- 18051281
TI  - Metagenomic analysis of BTEX-contaminated forest soil microcosm.
AB  - A microcosmal experiment using a metagenomic technique was designed to assess the
      effect of BTEX (benzene, toluene, ethylbenzene, and xylenes) on an indigenous
      bacterial community in a Daejeon forest soil. A compositional shift of bacterial
      groups in an artificial BTEX-contaminated soil was examined by the 16S rDNA PCR
      DGGE method. Phylogenetic analysis of 16S rDNAs in the dominant DGGE bands showed
      that the number of Actinobacteria and Bacillus populations increased. To confirm
      these observations, we performed PCR to amplify the 23S rDNA and 16S rDNA against
      the sample metagenome using Actinobacteria-targeting and Bacilli-specific primer
      sets, respectively. The result further confirmed that a bacterial community
      containing Actinobacteria and Bacillus was affected by BTEX.

PMID- 18051283
TI  - Bacterial surface display of GFP(uv) on bacillus subtilis spores.
AB  - To analyze a cotG-based Bacillus subtilis spore display system directly, GFP(uv)
      was expressed on the surface of Bacillus subtilis spores. When GFP(uv) was fused
      to the C-terminal of the cotG structural gene and expressed, the existence of a
      CotG-GFP(uv) fusion protein on the B. subtilis spore was confirmed by flow
      cytometry confocal microscopic analysis. When the cotG anchoring motif was
      deleted, no fluorescence emission was observed under flow cytometry and confocal
      microscopic analysis from the purified spore, confirming the essential role of
      CotG as an anchoring motif. This GFP(uv) displaying spore might be used for
      another signaling application triggered by intracellular or extracellular
      stimuli.

PMID- 18051282
TI  - Detection of methicillin resistance in Staphylococcus aureus isolates using two
      step triplex PCR and conventional methods.
AB  - A two-step triplex PCR assay targeting the mecA, femA, and nuc genes was
      developed for the detection of methicillin resistance genes harbored by some
      Staphylococcus aureus isolates and for the simultaneous identification of such
      isolates at the species level. The triplex PCR revealed the presence of the femA
      and nuc genes in all the S. aureus isolates examined (n=105). Forty-four clinical
      isolates were mecA positive and no foodborne isolates were mecA positive. The PCR
      results had a 98 or 99% correlation with the results of PBP2a latex agglutination
      tests or oxacillin susceptibility tests, respectively.

PMID- 18051284
TI  - Quantitative analysis of phosphinothricin-N-acetyltransferase in genetically
      modified herbicide tolerant pepper by an enzyme-linked immunosorbent assay.
AB  - An immunoassay method was developed to quantitatively detect phosphinothricin-N
      acetyltransferase (PAT) encoded by the Bialaphos resistance (bar) gene in
      genetically modified (GM) pepper. The histidine-tagged PAT was overexpressed in
      Escherichia coli M15 (pQE31-bar) and efficiently purified by Ni2+ affinity
      chromatography. A developed sandwich enzyme-linked immunosorbent assay (S-ELISA)
      method (detection limit: 0.01 microg/ml) was 100-fold more sensitive than a
      competitive indirect ELISA (CI-ELISA) method or Western blot analysis in
      detecting the recombinant PAT. In real sample tests, PAT in genetically modified
      herbicide-tolerant (GMHT) peppers was successfully quantified [4.9 +/- 0.4
      microg/g of sample (n = 6)] by the S-ELISA method. The S-ELISA method developed
      here could be applied to other GMHT crops and vegetables producing PAT.

PMID- 18051285
TI  - Cloning and expression of glucose-1-phosphate thymidylyltransferase gene (schS6)
      from Streptomyces sp. SCC-2136.
AB  - The deoxysugar biosynthetic gene cluster of Sch 47554/Sch 47555 was cloned from
      Streptomyces sp. SCC-2136. One of the ORFs, schS6, appeared to encode glucose-1
      phosphate thymidylyltransferase, which converts dTTP and glucose-1-phosphate to
      TDP-D-glucose and pyrophosphate. The dTDP-D-glucose is a key metabolite in
      prokaryotics as a precursor for a large number of modified deoxysugars, and these
      deoxysugars are a major part of various antibiotics, ranging from glycosides to
      macrolides. SchS6 was expressed in E. coli vector pSCHS6 and the expressed
      protein was purified to apparent homogeneity by ammonium sulfate precipitation
      and Ni-NTA affinity column chromatography. The specific activity of the purified
      enzyme increased 4.7-fold with 17.5% recovery. It migrated as a single band on
      SDS-PAGE with an apparent molecular mass of 56 kDa. The purified protein showed
      glucose-1-phosphate thymidylyltransferase activity, catalyzing a reversible
      bimolecular group transfer reaction. In the forward reaction, the highest
      activity was obtained with combination of dTTP and alpha-D-glucose-1-phosphate,
      and only 12% of that activity was obtained with the substrates UTP/alpha-D
      glucose-1-phosphate. In the opposite direction, the purified protein was highly
      specific for dTDP-D-glucose and pyrophosphate.

PMID- 18051286
TI  - Production of weak acid by anaerobic fermentation of soil and antifungal effect.
AB  - Acetic acid and butyric acid were produced by the anaerobic fermentation of soil
      mixed with wheat or rice bran. The concentration of acetic acid produced in the
      wheat and rice bran-treated soil was 31.2 mM and 8 mM, respectively, whereas the
      concentration of butyric acid in the wheat and rice bran-treated soil was 25.0 mM
      and 8 mM, respectively. The minimal fungicidal concentration (MFC) for all the
      fungal strains was 40-60 mM acetic acid, 20-40 mM butyric acid, and 40-60 mM
      mixture of acetic acid: butyric acid (1:1, v/v). Consequently, the efficacy of
      mixing wheat-bran with soil to control soil diseases was demonstrated.

PMID- 18051287
TI  - Characterization of cyclofructans from inulin by Saccharomyces cerevisiae Strain
      displaying cell-surface cycloinulooligosaccharide fructanotransferase.
AB  - The cycloinulooligosaccharide fructanotransferase (CFTase) gene (cft) from
      Paenibacillus macerans (GenBank access code AF222787) was expressed on the cell
      surface of Saccharomyces cerevisiae by fusing with Aga2p linked to the membrane
      anchored protein Aga1p. The surface display of CFTase was confirmed by
      immunofluorescence microscopy and enzymatic assay. The optimized reaction
      conditions of surface-displayed CFTase were as follows; pH, 8.0; temperature, 50
      degrees C; enzyme amount, 30 milliunit; substrate concentration, 5%; inulin
      source, Jerusalem artichoke. As a result of the reaction with inulin,
      cycloinulohexaose was produced as a major product along with cycloinuloheptaose
      and cycloinulooctaose as minor products.

PMID- 18051288
TI  - Comparison of full genome sequences between two hepatitis B virus strains with or
      without preC mutation (A1896) from a single Korean hepatocellular carcinoma
      patient.
AB  - This report describes the full-length sequences of 2 HBV clones from a
      hepatocellular carcinoma (HCC) patient, one with preC mutation (1896A) and the
      other without preC mutation. The high level of discrepancy in mutation frequency
      between these 2 strains was observed in the Core (C) region among 4 ORFs. These
      data support previous results that Korean HBV strains, belonging to genotype C2,
      are prone to mutations. It is possible that the mutations (BCP and preC
      mutations) associated with the HBeAg defective production might contribute to the
      diversity of mutations related to HBV persistence, playing an important role in
      hepatocarcinogenesis in this patient.

PMID- 18051289
TI  - Chitinophaga soli sp. nov. and Chitinophaga terrae sp. nov., isolated from soil
      of a ginseng field in Pocheon Province, Korea.
AB  - Two novel strains of the Cytophaga-Flexibacter-Bacteroides (CFB) group,
      designated Gsoil 219" and Gsoil 2381, were isolated from soil of a ginseng field
      of Pocheon Province in Korea. Both strains were Gram-negative, aerobic,
      nonmotile, nonspore-forming, and rod-shaped. Phylogenetic analysis based on 16S
      rRNA gene sequences indicated that both isolates belong to the genus Chitinophaga
      but were clearly separated from established species of this genus. The sequence
      similarities between strain Gsoil 219T and type strains of the established
      species and between strain Gsoil 238T and type strains of the established species
      ranged from 91.4 to 94.7% and 91.6 to 94.2%, respectively. Phenotypic and
      chemotaxonomic data (major menaquinone, MK-7; major fatty acids, iso-C15:0 and
      C(16:1) omega5c; major hydroxy fatty acid, iso-C(17:0) 3-OH; major polyamine,
      homospermidine) supported the affiliation of both strains Gsoil 219T and Gsoil
      238T to the genus Chitinophaga. Furthermore, the results of physiological and
      biochemical tests allowed genotypic and phenotypic differentiation of both
      strains from the other validated Chitinophaga species. Therefore, the two
      isolates represent two novel species, for which the name Chitinophaga soli sp.
      nov. (type strain, Gsoil 219T=KCTC 12650T=DSM 18093T) and Chitinophaga terrae sp.
      nov. (type strain, Gsoil 238T=KCTC 12651T=DSM 18078T) are proposed.

PMID- 18051290
TI  - Differences in optimal pH and temperature for cell growth and antibody production
      between two Chinese hamster ovary clones derived from the same parental clone.
AB  - To investigate clonal variations of recombinant Chinese hamster ovary (rCHO)
      clones in response to culture pH and temperature, serum-free suspension cultures
      of two antibody-producing CHO clones (clones A and B), which were isolated from
      the same parental clone by the limiting dilution method, were performed in a
      bioreactor at pH values in the range of 6.8-7.6, and two different temperatures,
      33 degrees C and 37 degrees C. In regard to cell growth, clone A and clone B
      displayed similar responses to temperature, although their degree of response
      differed. In contrast, clones A and B displayed different responses to
      temperature in regard to antibody production. In the case of clone A, no
      significant increase in maximum antibody concentration was achieved by lowering
      the culture temperature. The maximum antibody concentration obtained at 33
      degrees C (pH 7.4) and 37 degrees C (pH 7.0) were 82.0 +/- 2.6 and 73.2 +/- 4.1
      microg/ml, respectively. On the other hand, in the case of clone B, an
      approximately 2.5-fold increase in maximum antibody concentration was achieved by
      lowering the culture temperature. The enhanced maximum antibody concentration of
      clone B at 33 degrees C (132.6 +/- 14.9 microg/ml at pH 7.2) was due to not only
      enhanced specific antibody productivity but also to prolonged culture longevity.
      At 33 degrees C, the culture longevity of clone A also improved, but not as much
      as that of clone B. Taken together, CHO clones derived from the same parental
      clone displayed quite different responses to culture temperature and pH with
      regards antibody production, suggesting that environmental parameters such as
      temperature and pH should be optimized for each CHO clone.

PMID- 18051291
TI  - Synthesis of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) with
      thermostabilized low-specific L-threonine aldolase from Streptomyces coelicolor
      A3(2).
AB  - Stability-enhanced mutants, H44, 11-94, 5A2-84, and F8, of L-threonine aldolase
      (L-TA) from Streptomyces coelicolor A3(2) (SCO1085) were isolated by an error
      prone PCR followed by a high-throughput screening. Each of these mutant, had a
      single amino acid substitution: H177Y in the H44 mutant, A169T in the 11-94
      mutant, D104N in the 5A2-84 mutant and Fl81 in the F8 mutant. The residual L-TA
      activity of the wild-type L-TA after a heat treatment for 20 min at 60 degrees C
      was only 10.6%. However, those in the stability-enhanced mutants were 85.7% for
      the H44 mutant, 58.6% for the F8 mutant, 62.1% for the 5A2-84 mutant, and 67.6%
      for the 11-94 mutant. Although the half-life of the wild-type L-TA at 63 degrees
      C was 1.3 min, those of the mutant L-TAs were longer: 14.6 min for the H44
      mutant, 3.7 min for the 11-94 mutant, 5.8 min for the 5A2-84 mutant, and 5.0 min
      for the F8 mutant. The specific activity did not change in most of the mutants,
      but it was decreased by 45% in the case of mutant F8. When the aldol condensation
      of glycine and 3,4-dihydroxybenzaldehyde was studied by using whole cells of
      Escherichia coli containing the wild-type L-TA gene, L-threo-3,4
      dihydroxyphenylserine (L.-threo-DOPS) was successfully synthesized with a yield
      of 2.0 mg/ml after 20 repeated batch reactions for 100 h. However, the L-threo
      DOPS synthesizing activity of the enzyme decreased with increased cycles of the
      batch reactions. Compared with the wild-type L-TA, H44 L-TA kept its L-threo-DOPS
      synthesizing activity almost constant during the 20 repeated batch reactions for
      100 h, yielding 4.0 mg/ml of L-threo-DOPS. This result showed that H44 L-TA is
      more effective than the wild-type L-TA for the mass production of L-threo-DOPS.

PMID- 18051292
TI  - pT7MT, a metallothionein 2A-tagged novel prokaryotic fusion expression vector.
AB  - In the present article, a novel fusion expression vector for Escherichia coli was
      developed based on the pTORG plasmid, a derivative of pET32a. This vector, named
      pT7MT (GenBank Accession No DQ504436), carries a T7 promoter and it drives the
      downstream gene encoding Metallothionein 2A (MT2A). There are in-framed multiple
      cloning sites (MCS) downstream of the MT2A gene. A target gene can be cloned into
      the MCS and fused to the C-terminal of the MT2A gene in a compatible open reading
      frame (ORF) to achieve fusion expression. The metal-binding capability of MT2A
      allows the purification of fusion proteins by metal chelating affinity
      chromatogralhy, known as Ni2+-affinity chromatography. Using this expression
      vector, we successfully got the stable and high-yield expression of MT2A-GST and
      MT2A-Troponin I fusion proteins. These two proteins were easily purified from the
      supernatant of cell lysates by one-step Ni2+ -affinity chromatography. The final
      yields of MT2A-GST and MT2A-Troponin I were 30 mg/l and 28 mg/l in LB culture,
      respectively. Taken together, our data suggest that pT7MT can be applied as a
      useful expression vector for stable and high-yield production of fusion proteins.

PMID- 18051293
TI  - Partial purification and characterization of exoinulinase from Kluyveromyces
      marxianus YS-1 for preparation of high-fructose syrup.
AB  - An extracellular exoinulinase (2,1-beta-D fructan fructanohydrolase, EC 3.2.1.7),
      which catalyzes the hydrolysis of inulin into fructose and glucose, was purified
      23.5-fold by ethanol precipitation, followed by Sephadex G-100 gel permeation
      from a cell-free extract of Kluyveromyces marxianus YS-1. The partially purified
      enzyme exhibited considerable activity between pH 5 to 6, with an optimum pH of
      5.5, while it remained stable (100%) for 3 h at the optimum temperature of 50
      degrees C. Mn2+ and Ca2+ produced a 2.4-fold and 1.2-fold enhancement in enzyme
      activity, whereas Hg2+ and Ag2+ completely inhibited the inulinase. A preparation
      of the partially purified enzyme effectively hydrolyzed inulin, sucrose, and
      raffinose, yet no activity was found with starch, lactose, and maltose. The
      enzyme preparation was then successfully used to hydrolyze pure inulin and raw
      inulin from Asparagus racemosus for the preparation of a high-fructose syrup. In
      a batch system, the exoinulinase hydrolyzed 84.8% of the pure inulin and 86.7% of
      the raw Asparagus racemosus inulin, where fructose represented 43.6 mg/ml and
      41.3 mg/ml, respectively.

PMID- 18051294
TI  - Production of recombinant polyhedra containing Cry1Ac fusion protein in insect
      cell lines.
AB  - Insect cell lines and the control of infection for obtaining the maximum amount
      of polyhedrin-CrylAc-polyhedrin fusion protein from Bactrus in monolayer and
      suspension culture systems were tested. Growth rates of the Trichoplusia ni (High
      Five) cell line in both culture systems were better than the other insect cell
      lines, Spodoptera fiugiferda (Sf-9, Sf-21), Trichoplusia ni (Tn5), and Spodoptera
      exigua (Se301). The expression of the fusion protein in a monolayer culture
      showed that Se301 cells were 2.3-4.8 times more productive on a per cell basis
      than the other cell lines. However, in suspension culture, only High-Five cells
      were productive. High-Five cells infected with Bactrus at a multiplicity of
      infection (MOI) of 5 and a cell density of 3.0 x 10(5) cells per ml were more
      productive than the other infection condition in a suspension culture suitable
      for a large-scale production of baculovirus. In conclusion, for the large-scale
      production of Bactrus in vitro, High-Five cells showing good growth and high
      productivity are suitable.

PMID- 18051295
TI  - Purification and characterization of extracellular beta-glucosidase from
      Sinorhizobium kostiense AFK-13 and its algal lytic effect on Anabaena flos-aquae.
AB  - A beta-glucosidase from the algal lytic bacterium Sinorhizobium kostiense AFK-13,
      grown in complex media containing cellobiose, was purified to homogeneity by
      successive ammonium sulfate precipitation, and anion-exchange and gel-filtration
      chromatographies. The enzyme was shown to be a monomeric protein with an apparent
      molecular mass of 52 kDa and isoelectric point of approximately 5.4. It was
      optimally active at pH 6.0 and 40'C and possessed a specific activity of 260.4
      U/mg of protein against 4-nitrophenyl-beta-D-glucopyranoside (pNPG). A
      temperature-stability analysis demonstrated that the enzyme was unstable at 50
      degrees C and above. The enzyme did not require divalent cations for activity,
      and its activity was significantly suppressed by Hg+2 and Ag+, whereas sodium
      dodecyl sulfate (SDS) and Triton X-100 moderately inhibited the enzyme to under
      70% of its initial activity. In an algal lytic activity analysis, the growth of
      cyanobacteria, such as Anabaena flos-aquae, A. cylindrica, A. macrospora,
      Oscillatoria sancta, and Microcystis aeruginosa, was strongly inhibited by a
      treatment of 20 ppm/disc or 30 ppm/disc concentration of the enzyme.

PMID- 18051297
TI  - Biochemical and genetic characterization of arazyme, an extracellular
      metalloprotease produced from Serratia proteamaculans HY-3.
AB  - Serratia proteamaculans HY-3 isolated from the digestive tract of a spider
      produces an extracellular protease named arazyme, with an estimated molecular
      mass of 51.5 kDa. The purified enzyme was characterized as having high activities
      at wide pH and temperature ranges. We further characterized biochemical features
      of the enzymatic reactions under various reaction conditions. The protease
      efficiently hydrolyzed a broad range of protein substrates including albumin,
      keratin, and collagen. The dependence of enzymatic activities on the presence of
      metal ions such as calcium and zinc indicated that the enzyme is a
      metalloprotease, together with the previous observation that the proteolytic
      activity of the enzyme was not inhibited by aspartate, cysteine, or serine
      protease inhibitors, but strongly inhibited by 1,10-phenanthroline and EDTA. The
      araA gene encoding the exoprotease was isolated as a 5.6 kb BamHl fragment after
      PCR amplification using degenerate primers and subsequent Southern hybridization.
      The nucleotide sequence revealed that the deduced amino acid sequences shared
      extensive similarity with those of the serralysin family of metalloproteases from
      other enteric bacteria. A gene (inh) encoding a putative protease inhibitor was
      also identified immediately adjacent to the araA structural gene.

PMID- 18051298
TI  - Optimization of ascorbic acid-2-phosphate production from ascorbic acid using
      resting cell of Brevundimonas diminuta.
AB  - With the aim to produce ascorbic acid-2-phosphate (AsA-2-P) from L-ascorbic acid
      (AsA, Vitamin C), nine bacteria conferring the ability to transform AsA to AsA-2
      P were isolated from soil samples alongside known strains from culture
      collections. Most isolates were classified to the genus Brevundimonas by 16S
      phylogenetic analysis. Among them, Brevundimonas diminuta KACC 10306 was selected
      as the experimental strain because of its the highest productivity of AsA-2-P.
      The optimum set of conditions for the AsA-2-P production from AsA using resting
      cells as the source of the enzyme was also investigated. The optimum cultivation
      time was 16 h and the cell concentration was 120 g/l (wet weight). The optimum
      concentrations of AsA and pyrophosphate were 550 mM and 450 mM, respectively. The
      most effective buffer was 50 mM sodium formate. The optimum pH was 4.5 and
      temperature was 40 degrees C. Under the above conditions, 27.5 g/l of AsA-2-P was
      produced from AsA after 36 h of incubation, which corresponded to a 19.7%
      conversion efficiency based on the initial concentration of AsA.

PMID- 18051296
TI  - Diversity of Paenibacillus spp. in the rhizosphere of four sorghum (Sorghum
      bicolor) cultivars sown with two contrasting levels of nitrogen fertilizer
      assessed by rpoB-based PCR-DGGE and sequencing analysis.
AB  - The diversity of Paenibacillus species was assessed in the rhizospheres of four
      cultivars of sorghum sown in Cerrado soil amended with two levels of nitrogen
      fertilizer (12 and 120 kg/ha). Two cultivars (IS 5322-C and IS 6320) demanded the
      higher amount of nitrogen to grow, whereas the other two (FBS 8701-9 and IPA
      1011) did not. Using the DNA extracted from the rhizospheres, a Paenibacillus
      specific PCR system based on the RNA polymerase gene (rpoB) was chosen for the
      molecular analyses. The resulting PCR products were separated into community
      fingerprints by DGGE and the results showed a clear distinction between
      cultivars. In addition, clone libraries were generated from the rpoB fragments of
      two cultivars (IPA 1011 and IS 5322-C) using both fertilization conditions, and
      318 selected clones were sequenced. Analyzed sequences were grouped into 14
      Paenibacillus species. A greater diversity of Paenibacillus species was observed
      in cultivar IPA 1011 compared with cultivar IS 5322-C. Moreover, statistical
      analyses of the sequences showed that the bacterial diversity was more influenced
      by cultivar type than nitrogen fertilization, corroborating the DGGE results.
      Thus, the sorghum cultivar type was the overriding determinative factor that
      influenced the community structures of the Paenibacillus communities in the
      habitats investigated.

PMID- 18051299
TI  - Characterization and purification of acidocin 1B, a bacteriocin produced by
      Lactobacillus acidophilus GP1B.
AB  - In the present study, acidocin 1B, a bacteriocin produced by Lactobacillus
      acidophilus GP1B, exhibited profound inhibitory activity against a variety of LAB
      and pathogens, including Gram-negative bacteria, and its mode of action was to
      destabilize the cell wall, thereby resulting in bactericidal lysis. Acidocin 1B
      was found to be heat stable, because it lost no activity when it was heated up to
      95 degrees C for 60 min. It retained approximately 67% of the initial activity
      after storage for 30 days at 4 degrees C, and 50% of its initial activity after
      30 days at 25 degrees C and 37 degrees C. The molecular mass of acidocin 1B was
      estimated to be 4214.65 Da by mass spectrometry. Plasmid curing results indicated
      that a plasmid, designated as pLA1B, seemed to be responsible for both acidocin
      1B production and host immunity, and that the pLA1B could be transformed into
      competent cells of L. acidophilus ATCC 43121 by electroporation. Our findings
      indicate that the acidocin 1B and its producer strain may have potential value as
      a biopreservative in food systems.

PMID- 18051300
TI  - Removal of organic load from olive washing water by an aerated submerged
      biofilter and profiling of the bacterial community involved in the process.
AB  - The present work aims to use a biofilter technology (aerated submerged filters)
      for the aerobic transformation at laboratory-scale of olive washing water (OWW)
      generated in the first steps of olive oil processing, as well as the genetic
      profiling and identification to the species level of the bacteria involved in the
      formation of the biofilm, by means of TGGE. Chemical parameters, such as
      biological oxygen demand at five days (BOD5) and chemical oxygen demand (COD),
      decreased markedly (up to 90 and 85%, respectively) by the biological treatment,
      and the efficiency of the process was significantly affected by aeration and
      inlet flow rates. The total polyphenol content of inlet OWW was only moderately
      reduced (around 50% decrease of the inlet content) after the biofilter treatment,
      under the conditions tested. Partial 16S rRNA genes were amplified using total
      DNA extracted from the biofilm and separated by TGGE. Sequences of isolated bands
      were mostly affiliated to the alpha-subclass of Proteobacteria, and often
      branched in the periphery of bacterial genera commonly present in soil
      (Rhizobium, Reichenowia, Agrobacterium, and Sphingomonas). The data obtained by
      the experimentation at laboratory scale provided results that support the
      suitability of the submerged filter technology for the treatment of olive washing
      waters with the purpose of its reutilization.

PMID- 18051302
TI  - The brown-rot basidiomycete Fomitopsis palustris has the endo-glucanases capable
      of degrading microcrystalline cellulose.
AB  - Two endoglucanases with processive cellulase activities, produced from Fomitopsis
      palustris grown on 2% microcrystalline cellulose (Avicel), were purified to
      homogeneity by anion-exchange and gel filtration column chromatography systems.
      SDS-PAGE analysis indicated that the molecular masses of the purified enzymes
      were 47 kDa and 35 kDa, respectively. The amino acid sequence analysis of the 47
      kDa protein (EG47) showed a sequence similarity with fungal glycoside hydrolase
      family 5 endoglucanase from the white-rot fungus Phanerochaete chrysosporium. N
      terminal and internal amino acid sequences of the 35-kDa protein (EG35), however,
      had no homology with any other glycosylhydrolases, although the enzyme had high
      specific activity against carboxymethyl cellulose, which is a typical substrate
      for endoglucanases. The initial rate of Avicel hydrolysis by EG35 was relatively
      fast for 48 h, and the amount of soluble reducing sugar released after 96 h was
      100 microg/ml. Although EG47 also hydrolyzed Avicel, the hydrolysis rate was
      lower than that of EG35. Thin layer chromatography analysis of the hydrolysis
      products released from Avicel indicated that the main product was cellobiose,
      suggesting that the brown-rot fungus possesses processive EGs capable of
      degrading crystalline cellulose.

PMID- 18051301
TI  - Cloning and characterization of glycogen-debranching enzyme from
      hyperthermophilic archaeon Sulfolobus shibatae.
AB  - A gene encoding a putative glycogen-debranching enzyme in Sulfolobus shibatae
      (abbreviated as SSGDE) was cloned and expressed in Escherichia coli. The
      recombinant enzyme was purified to homogeneity by heat treatment and Ni-NTA
      affinity chromatography. The recombinant SSGDE was extremely thermostable, with
      an optimal temperature at 85 degrees C. The enzyme had an optimum pH of 5.5 and
      was highly stable from pH 4.5 to 6.5. The substrate specificity of SSGDE
      suggested that it possesses characteristics of both amylo-1,6-glucosidase and
      alpha-1,4-glucanotransferase. SSGDE clearly hydrolyzed pullulan to maltotrlose,
      and 6-O-alpha-maltosyl-beta-cyclodextrin (G2-beta-CD) to maltose and beta
      cyclodextrin. At the same time, SSGDE transferred maltooligosyl residues to the
      maltooligosaccharides employed, and maltosyl residues to G2-beta-CD. The enzyme
      preferentially hydrolyzed amylopectin, followed in a decreasing order by
      glycogen, pullulan, and amylose. Therefore, the present results suggest that the
      glycogen-debranching enzyme from S. shibatae may have industrial application for
      the efficient debranching and modification of starch to dextrins at a high
      temperature.

PMID- 18051303
TI  - Generation of a specific marker to discriminate Gacillus anthracis from other
      bacteria of the Bacillus cereus group.
AB  - Bacillus anthracis is a soil pathogen capable of causing anthrax that is closely
      related to several environmental species, including B. cereus, B. mycoides, and
      B. thuringiensis. DNA homology studies showed that B. anthracis, B. cereus, B.
      mycoides, and B. thuringiensis are closely related, with a high sequence
      homology. To establish a method to specifically detect B. anthracis in situations
      such as environmental contamination, we initially performed RAPD-PCR with a 10
      mer random primer and confirmed the presence of specific PCR bands only in B.
      anthracis species. One region specific for B. anthracis was cloned and sequenced,
      and an internal primer set was designed to amplify a 241-bp DNA fragment within
      the sequenced region. The PCR system involving these specific primer sets has
      practical applications. Using lyses methods to prepare the samples for PCR, it
      was possible to quickly amplify the 241-bp DNA segment from samples containing
      only a few bacteria. Thus, the PCR detection method developed in this study is
      expected to facilitate the monitoring of environmental B. anthracis
      contamination.

PMID- 18051304
TI  - Isolation and ars detoxification of arsenite-oxidizing bacteria from abandoned
      arsenic-contaminated mines.
AB  - The ecosystems of certain abandoned mines contain arsenic-resistant bacteria
      capable of performing detoxification when an ars gene is present in the bacterial
      genome. The ars gene has already been isolated from Pseudomonas putida and
      identified as a member of the membrane transport regulatory deoxyribonucleic acid
      family. The arsenite-oxidizing bacterial strains isolated in the present study
      were found to grow in the presence of 66.7 mM sodium arsenate (V; Na2HAsO4.7H2O),
      yet experienced inhibited growth when the sodium arsenite (III; NaAsO2)
      concentration was higher than 26 mM. Batch experiment results showed that
      Pseudomonas putida strain OS-5 completely oxidized 1 mM of As(III) to As(V)
      within 35 h. An arsB gene encoding a membrane transport regulatory protein was
      observed in arsenite-oxidizing Pseudomonas putida strain OS-5, whereas arsB,
      arsH, and arrA were detected in strain OS-19, arsD and arsB were isolated from
      strain RW-18, and arsR, arsD, and arsB were found in E. coli strain OS-80. The
      leader gene of arsR, -arsD, was observed in a weak acid position. Thus, for
      bacteria exposed to weak acidity, the ars system may cause changes to the
      ecosystems of As-contaminated mines. Accordingly, the present results suggest
      that arsR, arsD, arsAB, arsA, arsB, arsC, arsH, arrA, arrB, aoxA, aoxB, aoxC,
      aoxD, aroA, and aroB may be useful for arsenite-oxidizing bacteria in abandoned
      arsenic-contaminated mines.

PMID- 18051305
TI  - Cloning and characterization of a gene encoding phosphoketolase in a
      Lactobacillus paraplantarum isolated from Kimchi.
AB  - A gene coding for phosphoketolase, a key enzyme of carbohydrate catabolism in
      heterofermentative lactic acid bacteria (LAB), was cloned from a Lactobacillus
      paraplantarum C7 and expressed in Escherichia coli. The gene is 2502 bp long and
      codes for a 788-amino-acids polypeptide with a molecular mass of 88.7 kDa. A
      Shine-Dalgamo sequence (aaggag) and an inverted-repeat terminator sequence are
      located upstream and downstream of the phosphoketolase gene, respectively. The
      gene exhibits an identity of >52% with phosphoketolases of other LAB. The
      phosphoketolase of Lb. paraplantarum C7 (LBPK) contains several highly conserved
      phosphoketolase signature regions and typical thiamine pyrophosphate (TPP)
      binding sites, as reported for other TPP-dependent enzymes. The phosphoketolase
      gene was fused to a glutathione S-transferase (GST::LBPK) gene for purification.
      The GST::LBPK fusion protein was detected in the soluble fraction of a
      recombinant Escherichia coli BL21. The GST::LBPK fusion protein was purified with
      a yield of 4.32 mg/400 ml by GSTrap HP affinity column chromatography and
      analyzed by N-terminal sequencing. LBPK was obtained by factor Xa treatment of
      fusion protein and the final yield was 3.78 mg/400 ml. LBPK was examined for its
      N-terminal sequence and phosphoketolase activity. The K(M) and Vmax values for
      fructose-6-phosphate were 5.08 +/- 0.057 mM (mean +/- SD) and 499.21 +/- 4.33
      micromol/min/mg, respectively, and the optimum temperature and pH for the
      production of acetyl phosphate were 45 degrees C and 7.0, respectively.

PMID- 18051306
TI  - Cloning, sequencing, and characterization of the pradimicin biosynthetic gene
      cluster of Actinomadura hibisca P157-2.
AB  - Pradimicins are potent antifungal antibiotics having an unusual
      dihydrobenzo[alpha]naphthacenequinone aglycone substituted with D-alanine and
      sugars. Pradimicins are polyketide antibiotics produced by Actinomadura hibisca
      P157-2. The gene cluster involved in the biosynthesis of pradimicins was cloned
      and sequenced. The pradimicin gene cluster was localized to a 39-kb DNA segment
      and its involvement in the biosynthesis of pradimicin was proven by gene
      inactivation of prmA and prmB (ketosynthases alpha and beta). The pradimicin gene
      cluster consists of 28 open reading frames (ORFs), encoding a type II polyketide
      synthase (PKS), the enzymes involved in sugar biosynthesis and tailoring enzymes
      as well as two resistance proteins. The deduced proteins showed strong
      similarities to the previously validated gene clusters of angucyclic polyketides
      such as rubromycin, griseorhodin, and fredericamycin. From the pradimicin gene
      cluster, prmP3 encoding a component of the acetyl-CoA carboxylase complex was
      disrupted. The production levels of pradimicins of the resulting mutants
      decreased to 62% of the level produced by the wild-type strain, which indicate
      that the acetyl-CoA carboxylase gene would have a significant role in the
      production of pradimicins through supplying the extender unit precursor, malonyl
      CoA.

PMID- 18051307
TI  - Expression and purification of recombinant active prostate-specific antigen from
      Escherichia coli.
AB  - Human prostate-specific antigen (PSA), a 33 kDa serine protease with
      comprehensive homology to glandular kallikrein, is secreted from prostatic tissue
      into the seminal fluid and enters into the circulation. The level of PSA
      increases in the serum of patients with prostatic cancer and hence is widely
      employed as a marker of the disease status. In particular, an enzymatically
      active PSA that is a form cleaved at the N-terminal seven-amino-acids
      prosequence, APLILSR, of proPSA may play an important roll in the progression of
      prostate cancer. Thus, the presence of the active form would selectively
      discriminate the cancer from benign prostatic hyperplasia. In this study, we
      developed a convenient purification method for the acquisition of active PSA and
      proPSA. Recombinant proPSA and active PSA were expressed directly in Escherichia
      coli, easily and efficiently isolated from inclusion bodies, refolded, and
      purified. Moreover, the enzymatic activity of the recombinant active PSA was
      confirmed as serine protease using chromogenic chymotrypsin substrate. This
      purified active PSA could be further applied to scrutinize the biological or
      conformational characteristics of the protein and to develop specific diagnostic
      and/or therapeutic agents against prostate cancer.

PMID- 18051308
TI  - An efficient method for the extraction of astaxanthin from the red yeast
      Xanthophyllomyces dendrorhous.
AB  - This study investigated an efficient method for the extraction of astaxanthin
      from the red yeast Xanthophyllomyces dendrorhous. The extraction process
      comprised three steps: (1) cultivating the yeast; (2) treating the yeast culture
      suspension with microwaves to destroy the cell walls and microbodies; and (3)
      drying the yeast and extracting the astaxanthin pigment using ethanol, methanol,
      acetone, or a mixture of the three as the extraction solvent. Ultimately, various
      treatment tests were performed to determine the conditions for optimal pigment
      extraction, and the total carotenoid and astaxanthin contents were quantified. A
      frequency of 2,450 MHz, an output of 500 watts, and irradiation time of 60 s were
      the most optimum conditions for yeast cell wall destruction. Furthermore, optimal
      pigment extraction occurred when using a cell density of 10 g/l at 30 C over 24
      h, with a 10% volume of ethanol.

PMID- 18051309
TI  - Raceway cultivation of Spirulina platensis using underground water.
AB  - The semi-outdoor cultivation of Spirulina platensis was attempted using an
      underground-water-based medium. Occurrence of contaminant organisms such as
      Chlorella sp. and Chlamydomonas sp. was not found from a microscopic observation
      and bacteria were not detected from denaturing gradient gel electrophoresis
      (DGGE) analysis of PCR-amplified 16S rDNA during the cultivation, owing to pH
      control and the high quality of the underground water. The mean productivity was
      high at 10.5 g/m2/d with a range of 4.2-12.3 g/m2/d despite the unfavorable
      weather conditions of the rainy season. The cultivated S. platensis included a
      normal protein content of 58.9%. Consequently, the underground water improved the
      biomass productivity and the biomass quality because of an abundant
      supplementation of natural minerals and through a contaminant-free culture.

PMID- 18051310
TI  - Antibacterial activity of sophoraflavanone G isolated from the roots of Sophora
      flavescens.
AB  - This study investigated the antibacterial activities of sophoraflavanone G from
      Sophora flavescens in combination with two antimicrobial agents against oral
      bacteria. The combined effect of sophoraflavanone G and the antimicrobial agents
      was evaluated using the checkerboard method to obtain a fractional inhibitory
      concentration (FIC) index. The sophoraflavanone G+ampicillin (AM) combination was
      found to have a synergistic effect against S. mutans, S. sanguinis, S. sobrinus,
      S. gordonii, A. actinomycetemcomitans, F. nucleatum, P. intermedia, and P.
      gingivalis, whereas the sophoraflavanone G+gentamicin (GM) combination had a
      synergistic effect against S. sanguinis, S. criceti, S. anginosus, A.
      actinomycetemcomitans, F. nucleatum, P. intermedia, and P. gingivalis. Neither
      combination exhibited any antagonistic interactions (FIC index >4). In
      particular, the MICs/MBCs for all the bacteria were reduced to one-half - one
      sixteenth as a result of the drug combinations. A synergistic interaction was
      also confirmed by time-kill studies for nine bacteria where the checkerboard
      suggested synergy. Thus, a strong bactericidal effect was exerted through the
      drug combinations, plus in vitro data suggested that sophoraflavanone G combined
      with other antibiotics may be microbiologically beneficial rather than
      antagonistic.

PMID- 18051311
TI  - Redoxcitrinin, a biogenetic precursor of citrinin from marine isolate of fungus
      Penicillium sp.
AB  - A chemical analysis of the fermentation of the marine-derived fungus Penicillium
      sp. led to the isolation of a biogenetic precursor of citrinin, redoxcitrinin
      (1), together with polyketide mycotoxins, phenol A (2), citrinin H2 (3), 4
      hydroxymellein (4), citrinin (5), and phenol A acid (6). The structures of
      compounds 1-6 were determined on the basis of physicochemical data analyses.
      Among them, compounds 1-3 exhibited a potent radical scavenging activity against
      1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC50 values of 27.7, 23.4, and 27.2
      microM, respectively.

PMID- 18051312
TI  - Genetic and antigenic characterization of swine H1N2 influenza viruses isolated
      from Korean pigs.
AB  - H1N2 influenza viruses are circulating in pigs worldwide and cause considerable
      economic losses to the pig industry. We genetically analyzed the genes of our
      isolates from Korean pigs, and compared the antigenicity of our isolates with
      swine H1N2 viruses isolated from pigs in the U.S.A. In addition, we serologically
      surveyed the infection rate of swine H1N2 viruses in pigs. We found that H1N2
      isolates from Korean pigs are genetically more related to swine H1N2 viruses
      isolated from pigs in the U.S.A. than those in European countries. When
      antigenicity was compared, our isolates were weakly reacted to antibodies against
      swine H1N2 viruses isolated from pigs in the U.S.A. The serological surveillance
      using sera from pigs in Korea showed that about 46% was positive for H1N2
      viruses. Our results suggest that swine H1N2 viruses are widespread in Korean
      pigs, and the development of a vaccine against H1N2 viruses may help to control
      their infection in pigs.

PMID- 18051313
TI  - Microorganisms against Plasmodiophora brassicae.
AB  - In order to find microorganisms showing antifungal activities against
      Plasmodiophora brassicae, which causes club root, Korean salt-fermented fishery
      products were tested. Several fermented broths of microorgansims isolated from
      Ammodytes personatus fishery products showed high antifungal activities. The
      identification of microorganisms and their in vivo antifungal activities are
      reported herein.

PMID- 18051314
TI  - Prions and prion diseases: fundamentals and mechanistic details.
AB  - Prion diseases, often called transmissible spongiform encephalopathies (TSEs),
      are infectious diseases that accompany neurological dysfunctions in many
      mammalian hosts. Prion diseases include Creutzfeldt-Jakob disease (CJD) in
      humans, bovine spongiform encephalopathy (BSE, "mad cow disease") in cattle,
      scrapie in sheep, and chronic wasting disease (CWD) in deer and elks. The cause
      of these fatal diseases is a proteinaceous pathogen termed prion that lacks
      functional nucleic acids. As demonstrated in the BSE outbreak and its
      transmission to humans, the onset of disease is not limited to a certain species
      but can be transmissible from one host species to another. Such a striking nature
      ofprions has generated huge concerns in public health and attracted serious
      attention in the scientific communities. To date, the potential transmission
      ofprions to humans via foodbome infectiorn and iatrogenic routes has not been
      alleviated. Rather, the possible transmission of human to human or cervids to
      human aggravates the terrifying situation across the globe. In this review, basic
      features about prion diseases including clinical and pathological
      characteristics, etiology, and transmission of diseases are described. Based on
      recently accumulated evidences, the molecular and biochemical aspects of prions,
      with an emphasis on the molecular interactions involved in prion conversion that
      is critical during prion replication and pathogenesis, are also addressed.

PMID- 18051315
TI  - Tylosin production by Streptomyces fradiae using raw cornmeal in airlift
      bioreactor.
AB  - Using a 50-l airlift bioreactor, for the effective production of tylosin from
      Streptomyces fradiae TM-224 using raw cornmeal as the energy source, various
      environmental factors were studied in flask cultures. The maximum tylosin
      concentration was obtained at 32 degrees C and pH between 7.0 and 7.5. When seed
      was inoculated after 24 h of culture, the maximum tylosin concentration, 5.7 g/l,
      was obtained after 4 days of culture. Various concentrations of raw cornmeal were
      tested to investigate the optimum initial concentration for the tylosin
      production. An initial raw cornmeal concentration of 80 g/l gave the highest
      tylosin concentration, 5.8 g/l, after 5 days of culture. Of the various nitrogen
      sources, soybean meal and fish meal were found to be the most effective for the
      production of tylosin. In particular, with the optimal mixing ratio, 12 g/l of
      soybean meal to 14 g/l of fish meal, 7.2 g/l of tylosin was obtained after 5 days
      of culture. To compare raw cornmeal and glucose for the production oftylosin in
      the 50-1 airlift bioreactor for 10 days, fed-batch cultures were carried out
      under the optimum culture conditions. When raw corn meal was used as the energy
      source, the tylosin production increased with increasing culture time. The
      maximum tylosin concentration after 10 days of culture was 13.5 g/l, with a
      product yield from raw cornmeal of 0.123 g/g of consumed carbon source, which was
      about 7.2 times higher than that obtained when glucose was used as the carbon
      source.

PMID- 18051316
TI  - Generation of FISH probes using laser microbeam microdissection and application
      to clinical molecular cytogenetics.
AB  - Chromosome microdissection and the reverse FISH technique is one of the most
      useful methods for the identification of structurally abnormal chromosomes. In
      particular, the laser microbeam microdissection (LMM) method allows rapid
      isolation of a target chromosome or a specific region of chromosomes without
      damage of genetic materials and contamination. Isolated chromosomes were directly
      amplified by the degenerate oligonucleotide-primed polymerase chain reaction (DOP
      PCR), and then the FISH probes labeled with spectrum green- or spectrum red-dUTP
      were generated by nick-translation. Whole chromosome painting (WCP) probes were
      successfully generated from only 5 copies of the chromosome. With this method, we
      produced 24 WCP probes for each human chromosome. We also tried to characterize a
      marker chromosome, which seemed to be originated from chromosome 11 on
      conventional banding technique. The marker chromosomes were isolated by the LMM
      method and analyzed by reverse FISH. We elucidated that the marker chromosome was
      originated from the short arm of chromosome 5 (5p11-->pter). A fully automated
      and computer-controlled LMM method is a very simple laboratory procedure, and
      enables rapid and precise characterization of various chromosome abnormalities.

PMID- 18051317
TI  - The analysis and application of a recombinant monooxygenase library as a
      biocatalyst for the Baeyer-Villiger reaction.
AB  - Because of their selectivity and catalytic efficiency, BVMOs are highly valuable
      biocatalysts for the chemoenzymatic synthesis of a broad range of useful
      compounds. In this study, we investigated the microbial Baeyer-Villiger oxidation
      and sulfoxidation of thioanisole and bicyclo[3.2.0]hept-2-en-6-one using whole
      Escherichia coli cells that recombined with each of the Baeyer-Villiger
      monooxygenases originated from Pseudomonas aeruginosa PAO1 and two from
      Streptomyces coelicolor A3(2). The three BVMOs were identified in the microbial
      genome database by a recently described protein sequence motif; e.g., BVMO motif
      (FXGXXXHXXXW). The reaction products were identified as (R)-/(S)sulfoxide and 2
      oxabicyclo/3-oxabicyclo[3.3.0]oct-6-en-2-one by GC-MS analysis. Consequently,
      this study demonstrated that the three enzymes can indeed catalyze the Baeyer
      Villiger reaction as a biocatalyst, and effective annotation tools can be
      efficiently exploited as a source of novel BVMOs.

PMID- 18051318
TI  - Cloning, purification, and characterization of a new DNA polymerase from a
      hyperthermophilic archaeon, Thermococcus sp. NA1.
AB  - Genomic analysis of Thermococcus sp. NA revealed the presence of a 3,927-base
      pair (bp) family B-type DNA polymerase gene, TNA1_pol. TNA1_pol, without its
      intein, was overexpressed in Escherichia coli, purified using metal affinity
      chromatography, and characterized. TNA1_pol activity was optimal at pH 7.5 and 75
      degrees C. TNA1_pol was highly thermostable, with a half-life of 3.5 h at 100
      degrees C and 12.5 h at 95 degrees C. Polymerase chain reaction parameters of
      TNA1_pol such as error-rate, processivity, and extension rate were measured in
      comparison with rTaq, Pfu, and KOD DNA polymerases. TNA1_pol averaged one
      incorrect bp every 4.45 kilobases (kb), and had a processivity of 150 nucleotides
      (nt) and an extension rate of 60 bases/s. Thus, TNA1_pol has a much faster
      elongation rate than Pfu DNA polymerase with 7-fold higher fidelity than that of
      rTaq.

PMID- 18051319
TI  - Molecular modeling and its experimental verification for the catalytic mechanism
      of Candida antarctica lipase B.
AB  - Quantum mechanical and molecular dynamics simulation analysis has been performed
      on the model system for CALB (Candida antarctica lipase B) with esters to study
      the reaction mechanism and conformational preference of catalytic hydrolysis and
      the esterification reaction. Using quantum mechanical analysis, the ping-pong bi
      bi mechanism was applied and energies and 3-dimensional binding configurations of
      the whole reaction pathways were calculated. Further molecular dynamics
      simulation analysis was performed on the basis of the transition state obtained
      from quantum mechanical study to observe the effect of structures of,the
      substrates. Calculation results using substrates of different chain length and
      chiral configurations were compared for conformational preference. The calculated
      results showed very small influence on chain length, whereas chiral conformation
      showed big differences. Calculated results from molecular modeling studies have
      been compared qualitatively with the experimental data using racemic mixtures of
      (+/-)-cis-4-acetamido-cyclopent-2-ene-1-ethyl acetate as substrates.

PMID- 18051320
TI  - Cloning and characterization of squalene synthase (SQS) gene from Ganoderma
      lucidum.
AB  - This report provides the complete nucleotide sequences of the full-length cDNA
      encoding squalene synthase (SQS) and its genomic DNA sequence from a triterpene
      producing fungus, Ganoderma lucidum. The cDNA of the squalene synthase (SQS)
      (GenBank Accession Number: DQ494674) was found to contain an open reading frame
      (ORF) of 1,404 bp encoding a 468-amino-acid polypeptide, whereas the SQS genomic
      DNA sequence (GenBank Accession Number: DQ494675) consisted of 1,984 bp and
      contained four exons and three introns. Only one gene copy was present in the G
      lucidum genome. The deduced amino acid sequence of Ganoderma lucidum squalene
      synthase (Gl-SQS) exhibited a high homology with other fungal squalene synthase
      genes and contained six conserved domains. A phylogenetic analysis revealed that
      G. lucidum SQS belonged to the fungi SQS group, and was more closely related to
      the SQS of U. maydis than to those of other fungi. A gene expression analysis
      showed that the expression level was relatively low in mycelia incubated for 12
      days, increased after 14 to 20 days of incubation, and reached a relatively high
      level in the mushroom primordia. Functional complementation of Gl-SQS in a SQS
      deficient strain of Saccharomyces cerevisiae confirmed that the cloned cDNA
      encoded a squalene synthase.

PMID- 18051321
TI  - Effects of culture conditions on osteogenic differentiation in human mesenchymal
      stem cells.
AB  - Human bone marrow-derived mesenchymal stem cells (hBMMSCs) must differentiate
      into osteogenic cells to allow for successful bone regeneration. In this study,
      we investigated the effects of different combinations of three soluble osteogenic
      differentiation-inducing factors [L-ascorbic acid (AC), beta-glycerophosphate
      (betaG), and bone morphogenic protein-2 (BMP-2)] and the presence of a
      hydroxyapatite (HA) substrate on hBMMSC osteogenic differentiation in vitro.
      hBMMSCs were cultured in medium containing various combinations of the soluble
      factors on culture plates with or without HA coating. After 7 days of culture,
      alkaline phosphatase (ALP) activity, calcium deposition, and osteoprotegerin
      (OPG) and osteopontin (OPN) expression were measured. The effects of individual
      and combined factors were evaluated using a factorial analysis method. BMP-2
      predominantly affected expression of early markers of osteogenic differentiation
      (ALP and OPG). HA had the highest positive effect on OPN expression and calcium
      deposition. The interaction between AC, betaG, and HA had the second highest
      positive effect on ALP activity.

PMID- 18051322
TI  - Assessment of lipopolysaccharide-binding activity of Bifidobacterium and its
      relationship with cell surface hydrophobicity, autoaggregation, and inhibition of
      interleukin-8 production.
AB  - This study was performed to screen probiotic bifidobacteria for their ability to
      bind and neutralize lipopolysaccharides (LPS) from Escherichia coli and to verify
      the relationship between LPS-binding ability, cell surface hydrophobicity (CSH),
      and inhibition of LPS-induced interleukin-8 (IL-8) secretion by HT-29 cells of
      the various bifidobacterial strains. Ninety bifidobacteria isolates from human
      feces were assessed for their ability to bind fluorescein isothiocyanate (FITC)
      labeled LPS from E. coli. Isolates showing 30-60% binding were designated LPS
      high binding (LPS-H) and those with less than 15% binding were designated LPS-low
      binding (LPS-L). The CSH, autoaggregation (AA), and inhibition of LPS-induced IL
      8 release from HT-29 cells of the LPS-H and LPS-L groups were evaluated. Five
      bifidobacteria strains showed high levels of LPS binding, CSH, AA, and inhibition
      of IL-8 release. However, statistically significant correlations between LPS
      binding, CSH, AA, and reduction of IL-8 release were not found. Although we could
      isolate bifidobacteria with high LPS-binding ability, CSH, AA, and inhibition of
      IL-8 release, each characteristic should be considered as strain dependent.
      Bifidobacteria with high LPS binding and inhibition of IL-8 release may be good
      agents for preventing inflammation by neutralizing Gram-negative endotoxins and
      improving intestinal health.

PMID- 18051323
TI  - Bifidus fermentation increases hypolipidemic and hypoglycemic effects of red
      ginseng.
AB  - Antihyperlipidemic and antihyperglycemic effects of Red Ginseng (RG, steamed and
      dried root of Panax ginseng C. A. Meyer, family Araliaceae), major component of
      which is ginsenoside Rg3, and Bifidodoterium-fermented RG (FRG), major component
      of which is ginsenoside Rh2, were investigated. Orally administered RG and FRG
      potently reduced the serum triglyceride levels in corn-oil-induced
      hypertriglycemidemic mice as well as total cholesterol and triglyceride levels in
      Triton WR-1339-induced hyperlipidemic mice. Of the saponin and polysaccharide
      fractions of RG and FRG, the polysaccharide fraction inhibited postprandial blood
      glucose elevation of maltose- or starch-loaded mice and reduced the blood
      triglyceride levels in corn-oil-induced hypertriglycemidemic mice. The saponin
      fraction and its ginsenosides Rg3 and Rh2 reduced blood triglyceride and total
      cholesterol levels in Triton WR1339-induced hyperlipidemic mice. The inhibitory
      effect of FRG and its main constituents against hyperlipidemia and hyperglycemia
      in mice were more potent than those of RG. These findings suggest that
      hypolipidemic and hypoglycemic effects of RG can be enforced by Bifidus
      fermentation and FRG may improve hyperlipidemia and hyperglycemia.

PMID- 18051324
TI  - Inhibitory effects of cordycepin (3'-deoxyadenosine), a component of Cordyceps
      militaris, on human platelet aggregation induced by thapsigargin.
AB  - Cordycepin (3'-deoxyadenosine) is an adenosine analog, isolated from Cordyceps
      militaris, and it has been used as an anticancer and anti-inflammation ingredient
      in traditional Chinese medicine. We investigated the effects of cordycepin (3'
      deoxyadenosine) on human platelet aggregation, which was induced by thapsigargin,
      a tumor promoter, and determined the cytosolic free Ca2+ levels ([Ca2+]i) (an
      aggregation-stimulating molecule) and cyclic-guanosine monophosphate (cGMP) (an
      aggregation-inhibiting molecule). Cordycepin inhibited thapsigargin-induced
      platelet aggregation in a dose-dependent manner, and it clearly reduced the
      levels of [Ca+]i, which was increased by thapsigargin (1 microM) or U46619 (3
      microM). Cordycepin also increased the thapsigargin-reduced cGMP levels.
      Accordingly, our data demonstrated that cordycepin may have a beneficial effect
      on platelet aggregation-mediated thrombotic diseases through the [Ca2+]i
      regulating system such as cGMP.

PMID- 18051325
TI  - The effect of pulse electric field on accumulation of selenium in cells of
      Saccharomyces cerevisiae.
AB  - Cultures of Saccharomyces cerevisiae were subjected to the effect of PEF (pulse
      electric field) and a source of selenium. The culture period after which yeast
      cells were subjected to PEF treatment was optimized, as was the duration of the
      exposure. Optimization of the nutrient medium composition in S. cerevisiae
      cultures resulted in an over 1.8-fold increase in selenium accumulation with
      relation to cultures on the initial substrate. Optimization of the pH value and
      of culture duration resulted in selenium accumulation increase by approximately
      78%. A significant correlation was found between the accumulation of selenium in
      yeast cells and its concentration in the culture substrate. The highest
      accumulation of selenium in the biomass of yeast, approx. 240 microg/g d.m., was
      obtained after 15-min exposure to PEF on a 20-h culture. An approx. 50% higher
      content of selenium in cells was recorded, as compared with the control culture
      without the application of PEF.

PMID- 18051326
TI  - Biodegradation of endocrine-disrupting bisphenol A by white rot fungus Irpex
      lacteus.
AB  - Biodegradation of endocrine-disrupting bisphenol A was investigated with several
      white rot fungi (Irpex lacteus, Trametes versicolor, Ganoderma lucidum,
      Polyporellus brumalis, Pleurotus eryngii, Schizophyllum commune) isolated in
      Korea and two transformants of T versicolor (strains MrP 1 and MrP 13). I.
      lacteus degraded 99.4% of 50 mg/l bisphenol A in 3 h incubation and 100% in 12 h
      incubation. which was the highest degradation rate among the fungal strains
      tested. T. versicolor degraded 98.2% of 50 mg/l bisphenol A in 12 h incubation.
      Unexpectedly, the transformant of the Mn-repressed peroxidase gene of T.
      versicolor, strain MrP 1, degraded 76.5% of 50 mg/l bisphenol A in 12 h
      incubation, which was a lower degradation rate than wild-type T. versicolor. The
      removal of bisphenol A by I. lacteus occurred mainly by biodegradation rather
      than adsorption. Optimum carbon sources for biodegradation of bisphenol A by I.
      lacteus were glucose and starch, and optimum nitrogen sources were yeast extract
      and tryptone in a minimal salts medium; however, bisphenol A degradation was
      higher in nutrient-rich YMG medium than that in a minimal salts medium. The
      initial degradation of endocrine disruptors was accompanied by the activities of
      manganese peroxidase and laccase in the culture

PMID- 18051328
TI  - Development of a novel vector system for programmed cell lysis in Escherichia
      coli.
AB  - Although widely used as a host for recombinant protein production, Escherichia
      coli is unsuitable for massive screening of recombinant clones, owing to its poor
      secretion of proteins. A vector system containing T4 holin and T7 lysozyme genes
      under the control of the ptsG promoter derivative that is inducible in the
      absence of glucose was developed for programmed cell lysis of E. coli. Because E.
      coli harboring the vector grows well in the presence of glucose, but is lysed
      upon glucose exhaustion, the activity of the foreign gene expressed in E. coli
      can be monitored easily without an additional step for cell disruption after the
      foreign gene is expressed sufficiently with an appropriate concentration of
      glucose. The effectiveness of the vector was demonstrated by efficient screening
      of the amylase gene from a Bacillus subtilis genomic library. This vector system
      is expected to provide a more efficient and economic screening ofbioactive
      products from DNA libraries in large quantities.

PMID- 18051327
TI  - Production of monoclonal antibody against Listeria monocytogenes and its
      application to immunochromatography strip test.
AB  - An immunochromatography (ICG) strip test based on a monoclonal antibody for the
      rapid detection of L. monocytogenes in meat and processed-meat samples was
      developed in this study. A monoclonal antibody (MAb) specific to L. monocytogenes
      was produced from cloned hybridoma cells (FKLM-3B12-37) and used to develop an
      ICG strip test. The antibody showed a stronger binding to L. monocytogenes than
      other Listeria species, and a weak cross-reaction to S. aureus based on an ELISA.
      The detection limit of the ICG strip test was 10(5) cell/ml. In total, 116 meat
      and processed-meat samples were collected and analyzed using both the ICG strip
      test and a PCR. The ICG strip test and PCR indicated L. monocytogenes
      contamination in 34 and 27 meat samples, respectively. The 7 meat samples not
      identified as L. monocytogenes positive by the PCR were also tested using an API
      kit and found to be contaminated by Listeria species. In conclusion, the ICG
      strip test results agreed well with those obtained using the PCR and API kit.
      Thus, the developed ICG has potential use as a primary screening tool for L.
      monocytogenes in various foods and agricultural products, generating results
      within 20 min without complicated steps.

PMID- 18051329
TI  - Cloning of four genes involved in limonene hydroxylation from Enterobacter
      cowanii 6L.
AB  - Genes encoding proteins responsible for limonene catabolism were cloned from a
      limonene-degrading microorganism, Enterobacter cowanii 6L, which was isolated
      from citron (Citrus junos) peel. The 8.6, 4.7, and 7.7 kb fragments (CD3, CD4,
      and CD6) of E. cowanii 6L chromosomal DNA that confer to E. coli the ability to
      grow on limonene have been cloned and their corresponding DNA sequences were
      determined. Nine open reading frames (ORFs) were identified, and the four ORFs
      (921 bp of CD3-2; 1515 bp of CD4-1; 1776 bp of CD6-1; and 1356 bp of CD6-2) that
      encode limonene hydroxylase were confirmed by independently expressing these
      genes in E. coli. FAD and NADH were found to stimulate the hydroxylation reaction
      if added to cell extracts from E. coli recombinants, and multiple compounds
      (linalool, dihydrolinalool, perillyl alcohol, alpha-terpineol, and gamma
      terpineol) were the principal products observed. Our results suggest that the
      isolate E. cowanii 6L has a broad metabolic capability including utilization of
      limonene. This broad metabolic ability was confirmed by identifying four novel
      limonene hydroxylase functional ORFs in E. cowanii 6L.

PMID- 18051330
TI  - Simultaneous detection and identification of Bacillus cereus group bacteria using
      multiplex PCR.
AB  - Bacillus cereus group bacteria share a significant degree of genetic similarity.
      Thus, to differentiate and identify the Bacillus cereus group efficiently, a
      multiplex PCR method using the gyrB and groEL genes as diagnostic markers is
      suggested for simultaneous detection. The assay yielded a 400 bp amplicon for the
      groEL gene from all the B. cereus group bacteria, and a 253 bp amplicon from B.
      anthracis, 475 bp amplicon from B. cereus, 299 bp amplicon from B. thuringiensis,
      and 604 bp amplicon from B. mycoides for the gyrB gene. No nonspecific amplicons
      were observed with the DNA from 29 other pathogenic bacteria. The specificity and
      sensitivity of the B. cereus group identification using this multiplex PCR assay
      were evaluated with different kinds of food samples. In conclusion, the proposed
      multiplex PCR is a reliable, simple, rapid, and efficient method for the
      simultaneous identification of B. cereus group bacteria from food samples in a
      single tube.

PMID- 18051331
TI  - Effect of 3,3',4',5-tetrachlorosalicylanilide on reduction of excess sludge and
      nitrogen removal in biological wastewater treatment process.
AB  - A metabolic uncoupler, 3,3',4',5-tetrachlorosalicylanilide (TCS), was used to
      reduce excess sludge production in biological wastewater treatment processes.
      Batch experiments confirmed that 0.4 mg/l of TCS reduced the aerobic growth yield
      of activated sludge by over 60%. However, the growth yield remained virtually
      constant even at the increased concentrations of TCS when cultivations were
      carried out under the anoxic condition. Reduction of sludge production yield was
      confirmed in a laboratory-scale anoxic-oxic process operated for 6 months.
      However, it was found that ammonia oxidation efficiency was reduced by as much as
      77% in the presence of 0.8 mg/l of TCS in the batch culture. Similar results were
      also obtained through batch inhibition tests with activated sludges and by
      bioluminescence assays using a recombinant Nitrosomonas europaea (pMJ217).
      Because of this inhibitory effect of TCS on nitrification, the TCS-fed continuous
      system failed to remove ammonia in the influent. When TCS feeding was stopped,
      the nitrification yield of the process was resumed. Therefore, it seems to be
      necessary to assess the nitrogen content of wastewater if TCS is used for
      reducing sludge generation.

PMID- 18051332
TI  - Detection and kinetics of mucosal pathogenic bacteria binding with
      polysaccharides.
AB  - The detection and kinetics of mucosal pathogenic bacteria binding on
      polysaccharide ligands were studied using a surface plasmon resonance biosensor.
      The kinetic model applied curve-fitting to the experimental surface plasmon
      resonance sensorgrams to evaluate the binding interactions. The kinetic
      parameters for the mucosal pathogenic bacteria (Pseudomonas aeruginosa,
      Pseudomonasfluorescens, Serratia marcescens) with the alginate ligand were
      determined from a kinetic model. In addition, the binding interactions of the
      mucosal pathogenic bacteria with polysaccharide binding pairs (Pseudomonas
      aeruginosa/alginate, Streptococcus pneumoniae/pneumococcal polysaccharide,
      Staphylococcus aureus/pectin) were also compared with their kinetic parameters.
      The rate constants of association for Pseudomonas aeruginosa with the alginate
      ligand were higher than those for Pseudomonas fluorescens. Serratia marcescens
      had no detectable interaction with the alginate ligand. The adhesion affinity of
      Pseudomonas aeruginosa with alginate was higher than that for the other binding
      pairs. The binding affinities of the pathogenic bacteria with their own
      polysaccharide were higher than that of Staphylococcus aureus with pectin.
      Measuring the contact angle was found to be a feasible method for detecting
      binding interactions between analytes and ligands.

PMID- 18051333
TI  - Involvement of extracellular matrix and integrin-like proteins on conidial
      adhesion and appressorium differentiation in Magnaporthe oryzae.
AB  - Conidial adhesion and appressorium formation of Magnaporthe oryzae on the rice
      surface are important early events in the infection process. As an initiative
      step to understand the mechanisms underlying these cellular processes at a
      biochemical level, the effect of a human fibronectin antibody (HFA) and RGD
      peptides on conidial adhesion and appressorium formation was evaluated. HFA
      inhibited conidial adhesion and appressorium formation in a dosage-dependent
      manner. RGD peptides also inhibited these cellular events. Conidial adhesion and
      appressorium formation inhibited by RGD peptides were restored by chemicals
      involved in the cyclic AMP-dependent signaling pathway. These results suggest
      that extracellular matrix proteins might be involved in conidial adhesion and
      appressorium formation through integrin-like receptor mediation and modulation of
      cAMP-dependent signaling in the cells.

PMID- 18051334
TI  - Functional analysis of the residues C770 and G771 of E. coli 16S rRNA implicated
      in forming the intersubunit bridge B2c of the ribosome.
AB  - Structural analyses have shown that nucleotides at the positions 770 and 771 of
      Escherichia coli 16S rRNA are implicated in forming one of highly conserved
      intersubunit bridges of the ribosome, B2c. To examine a functional role of these
      residues, base substitutions were introduced at these positions and mutant
      ribosomes were analyzed for their protein synthesis ability using a specialized
      ribosome system. The results showed requirement of a pyrimidine at the position
      770 for ribosome function regardless of the nucleotide identity at the position
      771. Sucrose gradient profiles of ribosomes revealed that the loss of protein
      synthesis ability of mutant ribosome bearing a base substitution from C to G at
      the position 770 stems from its inability to form 70S ribosomes. These findings
      indicate involvement of nucleotide at the position 770, not 771, in ribosomal
      subunit association and provide a useful rRNA mutation that can be used as a
      target to investigate the physical interaction between 16S and 23S rRNA.

PMID- 18051335
TI  - Repeated batch production of epothilone B by immobilized Sorangium cellulosum.
AB  - Production of extracellular epothilone B, one of the potent anticancer agents, by
      free and immobilized Sorangium cellulosum was studied using the repeated batch
      culture process. The concentration of alginate used in immobilization was
      directly related to the mass transfer rate of nutrients, mechanical stability,
      and the epothilone B production yield. With the optimized 3% (w/v) calcium
      alginate carrier, a prolonged repeated batch culture was investigated for the 5
      repeated batches for 24 days. The maximum productivity of epothilone B obtained
      from the alginate-immobilized cells was 5.03 mg/l/day, which is 3 times higher
      than that of free cells (1.68 mg/l/day).

PMID- 18051336
TI  - Development of a monitoring vector for Leuconostoc mesenteroides using the green
      fluorescent protein gene.
AB  - The vector pCW5 with plasmid pC7, originally isolated in Lactobacillus
      paraplantarum C7 derived from kimchi, was constructed using a p32 strong
      promoter, the pC7 replicon, and green fluorescent protein (GFP) as the reporter.
      The constructed vector was transformed into E. coli and Leuconostoc
      mesenteroides, and GFP expression detected using a Western blot analysis. GFP
      fluorescence was recognized in E. coli and Leuconostoc mesenteroides using a
      confocal microscope. In addition, GFP fluorescence was also clearly detected in
      several industrially important lactic acid bacteria (LAB), including
      Lactobacillus bulgaricus, Lactobacillus paraplantarum, and Lactobacillus
      plantarum. Thus, pCW5 was shown to be effective for Leuconostoc mesenteroides
      when using GFP as the reporter, and it can also be used as a broad-host-range
      vector for other lactic acid bacteria.

PMID- 18051337
TI  - Antifungal cyclopeptolide from fungal saprophytic antagonist Ulocladium atrum.
AB  - The saprophytic fungus Ulocladium atrum Preuss is a promising biological control
      agent for Botrytis cinerea in greenhouse- and field-grown crops. However, despite
      its known potent antifungal activity, no antifungal substance has yet been
      reported. In an effort to characterize the antifungal substance from U atrum, we
      isolated an antibiotic peptide. Based on extensive spectroscopic analyses, its
      structure was established as a cyclopeptolide with a high portion of N-methylated
      amino acids, and its 1H and 13C chemical shifts were completely assigned based on
      extensive 1D and 2D NMR experiments. Compound 1 exhibited potent antifungal
      activity against the plant pathogenic fungus Botrytis cinerea and moderate
      activity against Alternaria alternate and Magnaporthe grisea.

PMID- 18051339
TI  - Role of oral appliances in the management of sleep bruxism and temporomandibular
      disorders.

PMID- 18051338
TI  - Batch and continuous culture kinetics for production of carotenoids by beta
      ionone-resistant mutant of Xanthophyllomyces dendrorhous.
AB  - A beta-ionone-resistant mutant strain isolated from the red yeast
      Xanthophyllomyces dendrorhous KCTC 7704 was used for batch and continuous
      fermentation kinetic studies with glucose media in a 2.5-1 jar fermentor at 22
      degrees C and pH 4.5. The kinetic pattern of growth and carotenoid concentration
      in the batch fermentations exhibited a so-called mixed-growth-associated product
      formation, possibly due to the fact that the content of intracellular carotenoids
      depends on the degree of physical maturation toward adulthood. To determine the
      maximum specific growth rate constant (microm) and Monod constant (k(s)) for the
      mutant, glucose-limited continuous culture studies were performed at different
      dilution rates within a range of 0.02-0.10 h(-1). A reciprocal plot of the steady
      state data (viz., reciprocal of glucose concentration versus residence time)
      obtained from continuous culture experiments was used to estimate a microm of
      0.15 h(-1) and k(s) of 1.19 g/l. The carotenoid content related to the residence
      time appeared to assume a typical form of saturation kinetics. The maximum
      carotenoid content (Xm) for the mutant was estimated to be 1.04 microg/mg dry
      cell weight, and the Lee constant (k(m)), which was tentatively defined in this
      work, was found to be 3.0 h.

PMID- 18051340
TI  - Evolution and integration of current restorative endodontic concepts.

PMID- 18051341
TI  - Understanding and managing dental caries: a medical approach.
AB  - This article has taken a medical approach toward the understanding and managing
      of dental caries. Caries has been defined as a point in a person's life when
      there is an imbalance between protective and pathologic factors such that the
      process of demineralization of tooth structure by acid from bacteria in the tooth
      biofilm exceeds the patient's ability to remineralized tooth structure. The
      patient diagnosed with caries is out of balance. Caries is a diagnosis of a
      person. People have caries, teeth have lesions. Caries lesion detection,
      classification, and analysis are done at the level of the tooth surface. Caries
      is a process in time. Today we establish a diagnosis. For the future we establish
      a prediction. Patients can be diagnosed as caries active, caries balanced, or
      caries undetermined. For an improved treatment plan, future risk and prognosis
      assessments are accomplished by classifying all patients as either low, moderate,
      or high risk. A combination of diagnosis and risk or prognosis assessment leads
      to five treatment groups, each with an appropriate protocol for managing the
      disease process. The five protocols follow from the use of the four-step medical
      model for caries management. In the end, there are two treatment plans for these
      patients: a restorative therapy plan that treats the holes and a disease
      management plan that treats the disease. Surgical treatment does not manage the
      disease. Today we are managing tooth decay with medicine instead of a drill.

PMID- 18051342
TI  - Ten fundamental components of dental practice management.

PMID- 18051343
TI  - Access to dental care: a social justice discussion.

PMID- 18051345
TI  - What is a Jewish dentist doing in church?

PMID- 18051344
TI  - Surgical soft tissue management.

PMID- 18051346
TI  - On the road again.

PMID- 18051347
TI  - Nanotechnology in biodevices.
AB  - Nanotechnology is the creation and utilization of materials, devices, and systems
      through the control of matter on the nanometer. The technology has been applied
      to biodevices such as bioelectronics and biochips to improve their performances.
      Nanoparticles, such as gold (Au) nanoparticles, are the most widely used of the
      various other nanotechnologies for manipulation at the nanoscale as well as
      nanobiosensors. The immobilization of biomolecules is playing an increasingly
      important role in the development of biodevices with high performance.
      Nanopatterning technology, which is able to increase the density of chip arrays,
      offers several advantages, including cost lowering, simultaneous multicomponent
      detection, and the efficiency increase of biochemical reactions. A microfluidic
      system incorporated with control of nanoliter of fluids is also one of the main
      applications of nanotechnologies. This can be widely utilized in the various
      fields because it can reduce detection time due to tiny amounts of fluids,
      increase signal-to-noise ratio by nanoparticles in channel, and detect multi
      targets simultaneously in one chamber. This article reviews nanotechnologies such
      as the application of nanoparticles for the detection of biomolecules, the
      immobilization of biomolecules at nanoscale, nanopatterning technologies, and the
      microfluidic system for molecular diagnosis.

PMID- 18051348
TI  - Identification and molecular characterization of novel cry1-type toxin genes from
      Bacillus thuringiensis K1 isolated in Korea.
AB  - To clone novel cry1-type genes from the Bacillus thuringiensis K1 isolate, about
      2.4-kb-long PCR fragments were amplified with two primer sets of ATG1-F/N400-R
      and 1BeATG1-F/N400-R. Using PCR-RFLP, three novel cry1-type genes, cry1-1, cry1
      7, and cry1-44, were obtained from B. thuringiensis K1 and the complete coding
      sequences of these novel genes were analyzed. The Cry1-1, Cry1-7, and Cry1-44
      proteins showed maximum similarities of about 78.0%, 99.7%, and 91.0% with the
      Cry1Ha1, Cry1Be1, and Cry1Ac2 proteins, respectively. These novel cry1-type genes
      were expressed using a baculovirus expression vector system and their
      insecticidal activities were investigated. Whereas all three novel genes were
      toxic to Plutella xylostella larvae, only Cry1-1 showed insecticidal activity
      against Spodoptera exigua larvae.

PMID- 18051349
TI  - Isolation and characterization of biopolymers extracted from the bark of
      Acanthopanax sessiliflorus and their anticomplement activity.
AB  - The crude biopolymer (AS-S1) and endo-biopolymer (AS-S2) were isolated from the
      dry stem bark of Acanthopanax sessiliflorus and tested for anti complement
      activity. The two potent anticomplement biopolymers, AS-1 and AS-2-Fr.I, were
      isolated by the combination of ion-exchange chromatography and gel filtration
      methods from the endo-biopolymers (AS-S2). The anticomplement activity of AS-1
      (MW 12 kDa) and AS-2-Fr.I (MW 180 kDa) were found to be 84.4% and 100.0%,
      respectively, at the concentration of 25 microg/ml. Activated pathway of the
      complement system occurred in both classical and alternative pathways, as
      evidenced by crossed immunoelectrophoresis (CIEP), where a major pathway was
      detected to be the classical one. It was found that the anticomplement activities
      of the periodate oxidized were decreased significantly, but those of pronase
      digested biopolymers of AS-1 and AS-2-Fr.I were decreased very little. The AS-1
      contained 2,4,6-tri-O-methyl-D-glucitol, 2,3,6-tri-O-methyl-D-glucitol, and 2,3,6
      tri-O-methyl-D-galacitol, which indicated that AS-1 contained a (1 --> 3), (1 -->
      4)-linked glucopyranosyl residue and a (1 --> 4)-linked galactosyl residue. AS-2
      Fr.I contained mainly 2,4-di-O-methyl-D-mannitol and 2,3,4-tri-O-methyl-D
      galacitol, which contained (1 --> 3), (1 --> 6) linked mannosyl and (1 --> 6)
      linked galactosyl residues.

PMID- 18051350
TI  - Cloning, characterization, and expression of xylanase A gene from Paenibacillus
      sp. DG-22 in Escherichia coli.
AB  - The xynA gene encoding the xylanase A of Paenibacillus sp. DG-22 was isolated
      with a DNA probe obtained by PCR amplification, using degenerated primers deduced
      from the amino acid residues of the known N-terminal region of the purified
      enzyme and the conserved region in the family 11 xylanases. The positive clones
      were screened on the LB agar plates supplemented with xylan, by the Congo-red
      staining method. The xynA gene consists of a 630-bp open reading frame encoding a
      protein of 210 amino acids, and the XynA preprotein contains a 28-residues signal
      peptide whose cleavage yields a 182-residues mature protein of a calculated
      molecular weight of 20,000 Da and pI value of 8.77. The cloned DNA fragment also
      has another ORF of 873 nucleotides that showed 76% identity to the putative
      transcriptional activator of Bacillus halodurans C-125. Most of the xylanase
      activity was found in the periplasmic space of E. coli. The xynA gene was
      subcloned into pQE60 expression vector to fuse with six histidine-tag. The
      recombinant xylanase A was purified by heating and immobilized metal affinity
      chromatography. The optimum pH and temperature of the purified enzyme were 6.0
      and 60 degrees C, respectively. This histidine-tagged xylanase A was less
      thermostable than the native enzyme.

PMID- 18051351
TI  - Cloning, expression, and characterization of Bacillus sp. snu-7 inulin
      fructotransferase.
AB  - A gene encoding inulin fructotransferase (di-D-fructofuranose 1,2': 2,3'
      dianhydride [DFA III]-producing IFTase, EC 4.2.2.18) from Bacillus sp. snu-7 was
      cloned. This gene was composed of a single, 1,353-bp open reading frame encoding
      a protein composed of a 40-amino acid signal peptide and a 410-amino acid mature
      protein. The deduced amino acid sequence was 98% identical to Arthrobacter
      globiformis C11-1 IFTase (DFA III-producing). The enzyme was successfully
      expressed in E. coli as a functionally active, His-tagged protein, and it was
      purified in a single step using immobilized metal affinity chromatography. The
      purified enzyme showed much higher specific activity (1,276units/mg protein) than
      other DFA III-producing IFTases. The recombinant and native enzymes were
      optimally active in very similar pH and temperature conditions. With a 103-min
      half-life at 60 degrees C, the recombinant enzyme was as stable as the native
      enzyme. Acidic residues and cysteines potentially involved in the catalytic
      mechanism are proposed based on an alignment with other IFTases and a DFA IIIase.

PMID- 18051352
TI  - Isolation and characterization of mucous exopolysaccharide (EPS) produced by
      Vibrio furnissii strain VB0S3.
AB  - Marine bacterial strains were isolated from coastal regions of Goa and screened
      for the strains that produce the highest amount of mucous exopolysaccharide
      (EPS). Our screening resulted in the identification of the strain Vibrio
      furnissii VB0S3 (hereafter called VB0S3), as it produced the highest EPS in batch
      cultures during the late logarithmic growth phase. The isolate was identified as
      VB0S3 based on morphological and biochemical properties. Growth and EPS
      production were studied in mineral salts medium supplemented with NaCl (1.5%) and
      glucose (0.2%). The exopolymer was recovered from the culture supernatant by
      using three volumes of cold ethanol precipitation and dialysis procedure.
      Chemical analyses of EPS revealed that it is primarily composed of neutral
      sugars, uronic acids, and proteins. Fourier-transform infrared (FT-IR)
      spectroscopy revealed the presence of carboxyl, hydroxyl, and amide groups, which
      correspond to a typical heteropolymeric polysaccharide, and the EPS also
      possessed good emulsification activity. The gas chromatographic analysis of an
      alditol-acetate derivatized sample of EPS revealed that it was mainly composed of
      galactose and glucose. Minor components found were mannose, rhamnose, fucose,
      ribose, arabinose, and xylose. EPS was readily isolated from culture
      supernatants, which suggests that the EPS was a slime-like exopolysaccharide.
      This is the first report of exopolysaccharide characterization that describes the
      isolation and characterization of an EPS expressed by Vibrio furnissii strain
      VB0S3. The results of the study contribute significantly and go a long way
      towards an understanding of the correlation between growth and EPS production,
      chemical composition, and industrial applications of the exopolysaccharide in
      environmental biotechnology and bioremediation.

PMID- 18051353
TI  - Microcosm study for revegetation of barren land with wild plants by some plant
      growth-promoting rhizobacteria.
AB  - Growth promotion of wild plants by some plant growth-promoting rhizobacteria
      (PGPR) was examined in the microcosms composed of soils collected separately from
      a grass-covered site and a nongrass-covered site in a lakeside barren area at
      Lake Paro, Korea. After sowing the seeds of eight kinds of wild plants and
      inoculation of several strains of PGPR, the total bacterial number and microbial
      activity were measured during 5 months of study period, and the plant biomasses
      grown were compared at the end of the study. Acridine orange direct counts in the
      inoculated microcosms, 1.3-9.8 x 10(9) cells x g soil(-1) in the soil from the
      grass-covered area and 0.9-7.2 x 10(9) cells x g soil(-1) in the soil from the
      nongrass-covered site, were almost twice higher than those in the uninoculated
      microcosms. The number of Pseudomonas sp., well-known bacteria as PGPR, and the
      soil dehydrogenase activity were also higher in the inoculated soils than the
      uninoculated soils. The first germination of sowed seeds in the inoculated
      microcosm was 5 days earlier than the uninoculated microcosm. Average lengths of
      all plants grown during the study period were 26% and 29% longer in the
      inoculated microcosms starting with the grass-covered soil and the nongrass
      covered soil, respectively, compared with those in the uninoculated microcosms.
      Dry weights of whole plants grown were 67-82% higher in the inoculated microcosms
      than the uninoculated microcosms. Microbial population and activity and growth
      promoting effect by PGPR were all higher in the soils collected from the grass
      covered area than in the nongrass-covered area. The growth enhancement of wild
      plants seemed to occur by the activities of inoculated microorganisms, and this
      capability of PGPR may be utilized for rapid revegetation of some barren lands.

PMID- 18051354
TI  - Cloning and overexpression of a Paenibacillus beta-glucanase in Pichia pastoris:
      purification and characterization of the recombinant enzyme.
AB  - Isolation, expression, and characterization of a novel endo-beta-1,3(4)-D
      glucanase with high specific activity and homology to Bacillus lichenases is
      described. One clone was screened from a genomic library of Paenibacillus sp. F
      40, using lichenan-containing plates. The nucleotide sequence of the clone
      contains an ORF consisting of 717 nucleotides, encoding a beta-glucanase protein
      of 238 amino acids and 26 residues of a putative signal peptide at its N
      terminus. The amino acid sequence showed the highest similarity of 87% to other
      beta-1,3-1,4-glucanases of Bacillus. The gene fragment Bg1 containing the mature
      glucanase protein was expressed in Pichia pastoris at high expression level in a
      3-1 high-cell-density fermenter. The purified recombinant enzyme Bgl showed
      activity against barley beta-glucan, lichenan, and laminarin. The gene encodes an
      endo-beta-1,3(4)-D-glucanase (E. C. 3.2.1.6). When lichenan was used as
      substrate, the optimal pH was 6.5, and the optimal temperature was 60 degrees C.
      The K(m), V(max), and k(cat) values for lichenan are 2.96 mg/ml, 6,951
      micromol/min x mg, and 3,131 s(-1), respectively. For barley beta-glucan the
      values are 3.73 mg/ml, 8,939 micromol/min x mg, and 4,026 s(-1), respectively.
      The recombinant Bg1 had resistance to pepsin and trypsin. Other features of
      recombinant Bg1 including temperature and pH stability, and sensitivity to some
      metal ions and chemical reagents were also characterized.

PMID- 18051355
TI  - Monitoring of microbial diversity and activity during bioremediation of crude oil
      contaminated soil with different treatments.
AB  - The present study compared the microbial diversity and activity during the
      application of various bioremediation processes to crude oil-contaminated soil.
      Five different treatments, including natural attenuation (NA), biostimulation
      (BS), biosurfactant addition (BE), bioaugmentation (BA), and a combined treatment
      (CT) of biostimulation, biosurfactant addition, and bioaugmentation, were used to
      analyze the degradation rate and microbial communities. After 120 days, the level
      of remaining hydrocarbons after all the treatments was similar, however, the
      highest rate (k) of total petroleum hydrocarbon (TPH) degradatioN was observed
      with the CT treatment (P < 0.05). The total bacterial counts increased during the
      first 2 weeks with all the treatments, and then remained stable. The bacterial
      communities and alkane monooxygenase gene fragment, alkB, were compared by
      denaturing gradient gel electrophoresis (DGGE). The DGGE analyses of the BA and
      CT treatments, which included Nocardia sp. H17-1, revealed a simple dominant
      population structure, compared with the other treatments. The Shannon-Weaver
      diversity index (H') and Simpson dominance index (D), calculated from the DGGE
      profiles using 16S rDNA, showed considerable qualitative differences in the
      community structure before and after the bioremediation treatment as well as
      between treatment conditions.

PMID- 18051356
TI  - Molecular cloning and functional expression of esf gene encoding enantioselective
      lipase from Serratia marcescens ES-2 for kinetic resolution of optically active
      (S)-flurbiprofen.
AB  - An enantioselective lipase gene (esf) for the kinetic resolution of optically
      active (S)-flurbiprofen was cloned from the new strain Serratia marcescens ES-2.
      The esf gene was composed of a 1,845-bp open reading frame encoding 614 amino
      acid residues with a calculated molecular mass of 64,978 Da. The lipase expressed
      in E. coli was purified by a three-step procedure, and it showed preferential
      substrate specificity toward the medium-chain-length fatty acids. The esf gene
      encoding the enantioselective lipase was reintroduced into the parent strain S.
      marcescens ES-2 for secretory overexpression. The transformant S. marcescens BESF
      secreted up to 217 kU/ ml of the enantioselective lipase, about 54-fold more than
      the parent strain, after supplementing 3.0% Triton X-207. The kinetic resolution
      of (S)-flurbiprofen was carried out even at an extremely high (R,S)-flurbiprofen
      ethyl ester [(R,S)-FEE] concentration of 500 mM, 130 kU of the S. marcescens ES-2
      lipase per mmol of (R,S)-FEE, and 1,000 mM of succinyl beta-cyclodextrin as the
      dispenser at 37 degrees C for 12 h, achieving the high enantiomeric excess and
      conversion yield of 98% and 48%, respectively.

PMID- 18051357
TI  - Distinct regulation of the sprC gene encoding Streptomyces griseus protease C
      from other chymotrypsin genes in Streptomyces griseus IFO13350.
AB  - The sprC gene encodes Streptomyces griseus protease C (SGPC), a bacterial
      chymotrypsin-like serine protease. Because the published data on sprC was not
      complete, we cloned and analyzed a new DNA fragment spanning downstream to
      upstream of the sprC gene from S. griseus IFO13350. The cloned 2.3-kb DNA
      fragment was placed on a high-copy number plasmid and introduced into
      Streptomyces lividans TK24. Chymotrypsin activity of the transformant was 8.5
      times higher than that of the control after 3 days of cultivation and stably
      maintained until 9 days of cultivation, which clearly indicated that the cloned
      2.3-kb fragment contained the entire sprC gene with its own promoter. When the
      same construct was introduced in the S. griseus IFO13350 (wild strain) and its
      two mutant strains in the A-factor regulatory cascade, deltaadpA and HO1, the
      chymotrypsin activity increased fivefold only in the deltaadpA strain.
      Transcriptional analysis based on RT-PCR revealed that the sprC gene is normally
      transcribed in both strains; however, earlier transcription was observed in the
      wild strain compared with the deltaadpA strain. A gel mobility shift assay showed
      that the AdpA protein did not bind to the promoter region of sprC. All these data
      clearly indicate that the expression of sprC is not dependent on the AdpA
      protein, but is distinctly regulated from other chymotrypsin genes composing an
      AdpA regulon. Earlier morphological differentiation was observed in S. lividans
      TK24, and S. griseus IFO13350 and HO1, transformed with the expression vector.
      The transformant of S. griseus deltaadpA formed markedly larger colonies.
      Antisense repression of sprC resulted in severe decrease of chymotrypsin
      activity, down to one-third of the control, and delayed morphological
      differentiation. All these data suggest that SGPC is related to normal
      morphogenesis in S. griseus.

PMID- 18051358
TI  - Enhanced proteomic analysis of Streptomyces peucetius cytosolic protein using
      optimized protein solubilization protocol.
AB  - Improvements in the dissolution of proteins in two-dimensional gel
      electrophoresis have greatly advanced the ability to analyze the proteomes of
      microorganisms under a wide variety of physiological conditions. This study
      examined the effect of various combinations of chaotropic agents, a reducing
      agent, and a detergent on the dissolution of the Streptomyces peucetius cytosolic
      proteins. The use of urea alone in a rehydration buffer as a chaotropic agent
      gave the proteome a higher solubility than any of the urea and thiourea
      combinations, and produced the highest resolution and clearest background in two
      dimensional gel electrophoresis. Two % CHAPS, as a detergent in a rehydration
      buffer, improved the protein solubility. After examining the effect of several
      concentrations of reducing agent, 50 mM DTT in a rehydration buffer was found to
      be an optimal condition for the proteome analysis of Streptomyces. Using this
      optimized buffer condition, more than 2,000 distinct and differentially expressed
      soluble proteins could be resolved using two-dimensional gel electrophoresis with
      a pI ranging from 4-7. Under this optimized condition, 15 novel small proteins
      with low-level expression, which could not be analyzed under the non-optimized
      conditions, were identified. Overall, the optimized condition helped produce a
      better reference gel for Streptomyces peucetius.

PMID- 18051359
TI  - Two bacterial entophytes eliciting both plant growth promotion and plant defense
      on pepper (Capsicum annuum L.).
AB  - Plant growth-promoting rhizobacteria (PGPR) have the potential to be used as
      microbial inoculants to reduce disease incidence and severity and to increase
      crop yield. Some of the PGPR have been reported to be able to enter plant tissues
      and establish endophytic populations. Here, we demonstrated an approach to screen
      bacterial endophytes that have the capacity to promote the growth of pepper
      seedlings and protect pepper plants against a bacterial pathogen. Initially, out
      of 150 bacterial isolates collected from healthy stems of peppers cultivated in
      the Chungcheong and Gyeongsang provinces of Korea, 23 putative endophytic
      isolates that were considered to be predominating and representative of each
      pepper sample were selected. By phenotypic characterization and partial 16S rDNA
      sequence analysis, the isolates were identified as species of Ochrobacterium,
      Pantoea, Pseudomonas, Sphingomonas, Janthinobacterium, Ralstonia, Arthrobacter,
      Clavibacter, Sporosarcina, Acidovorax, and Brevundimonas. Among them, two
      isolates, PS4 and PS27, were selected because they showed consistent colonizing
      capacity in pepper stems at the levels of 10(6)-10(7) CFU/g tissue, and were
      found to be most closely related to Pseudomonas rhodesiae and Pantoea ananatis,
      respectively, by additional analyses of their entire 16S rDNA sequences.
      Drenching application of the two strains on the pepper seedlings promoted
      significant growth of peppers, enhancing their root fresh weight by 73.9% and
      41.5%, respectively. The two strains also elicited induced systemic resistance of
      plants against Xanthomonas axonopodis pv. vesicatoria.

PMID- 18051360
TI  - Production of gamma-aminobutyric acid (GABA) by Lactobacillus buchneri isolated
      from kimchi and its neuroprotective effect on neuronal cells.
AB  - Lactic acid bacteria that accumulated gamma-aminobutyric acid (GABA) in culture
      medium were screened to identify strains with high GABA-producing ability. One
      strain, MS, which was isolated from kimchi, showed the highest GABA-producing
      ability among the screened strains. MS was identified as Lactobacillus buchneri
      based on Gram-staining, metabolic characteristics, and 16S rDNA sequence
      determination. Optimum culture conditions for GABA production were determined:
      MRS broth containing 5% MSG, 1% NaCl, and 1% glucose, at an initial pH of 5.0,
      the incubation temperature at 30 degrees C for 36 h. Under these conditions, MS
      produced GABA at a concentration of 251 mM with a 94% GABA conversion rate.
      Moreover, culture extracts of Lb. buchneri MS partially or completely protected
      neuronal cells against neurotoxicant-induced cell death.

PMID- 18051361
TI  - Enrichment of electrochemically active bacteria using a three-electrode
      electrochemical cell.
AB  - Electrochemically active bacteria were successfully enriched in an
      electrochemical cell using a positively poised working electrode. The positively
      poised working electrode (+0.7 V vs. Ag/AgCl) was used as an electron acceptor
      for enrichment and growth of electrochemically active bacteria. When activated
      sludge and synthetic wastewater were fed to the electrochemical cell, a gradual
      increase in amperometric current was observed. After a period of time in which
      the amperometric current was stabilized (generally 8 days), linear correlations
      between the amperometric signals from the electrochemical cell and added BOD
      (biochemical oxygen demand) concentrations were established. Cyclic voltammetry
      of the enriched electrode also showed prominent electrochemical activity. When
      the enriched electrodes were examined with electron microscopy and confocal
      scanning laser microscopy, a biofilm on the enriched electrode surface and
      bacterium-like particles were observed. These experimental results indicate that
      the electrochemical system in this study is a useful tool for the enrichment of
      an electrochemically active bacterial consortium and could be used as a novel
      microbial biosensor.

PMID- 18051362
TI  - Development of bioreactor system for L-tyrosine synthesis using thermostable
      tyrosine phenol-lyase.
AB  - An efficient enzyme system for the synthesis of L-tyrosine was developed using a
      fed-batch reactor with continuous feeding of phenol, pyruvate, and ammonia. A
      thermo- and chemostable tyrosine phenol-lyase from Symbiobacterium toebii was
      employed as the biocatalyst in this work. The enzyme was produced using a
      constitutive expression system in Escherichia coli BL21, and prepared as a
      soluble extract by rapid clarification, involving treatment with 40% methanol in
      the presence of excess ammonium chloride. The stability of the enzyme was
      maintained for at least 18 h under the synthesis conditions, including 75 mM
      phenol at pH 8.5 and 40 degrees C. The fed-batch system (working volume, 0.5 1)
      containing 1.0 kU of the enzyme preparation was continuously fed with two
      substrate preparations: one containing 2.2 M phenol and 2.4 M sodium pyruvate,
      and the other containing 0.4 mM pyridoxal-5-phosphate and 4 M ammonium chloride
      (pH 8.5). The system produced 130 g/l of L-tyrosine within 30 h, mostly as
      precipitated particles, upon continuous feeding of the substrates for 22 h. The
      maximum conversion yield of L-tyrosine was 94% on the basis of the supplied
      phenol.

PMID- 18051364
TI  - Ectopic expression of apple MbR7 gene induced enhanced resistance to transgenic
      Arabidopsis plant against a virulent pathogen.
AB  - A disease resistance related gene, MbR7, was identified in the wild apple
      species, Malus baccata. The MbR7 gene has a single open reading frame (ORF) of
      3,288 nucleotides potentially encoding a 1,095-amino acid protein. Its deduced
      amino acid sequence resembles the N protein of tobacco and the NL27 gene of
      potato and has several motifs characteristic of a TIR-NBS-LRR R gene subclass.
      Ectopic expression of MbR7 in Arabidopsis enhanced the resistance against a
      virulent pathogen, Pseudomonas syringae pv. tomato DC3000. Microarray analysis
      confirmed the induction of defense-related gene expression in 35S::MbR7
      heterologous Arabidopsis plants, indicating that the MbR7 gene likely activates a
      downstream resistance pathway without interaction with pathogens. Our results
      suggest that MbR7 can be a potential target gene in developing a new disease
      resistant apple variety.

PMID- 18051363
TI  - Molecular cloning and characterization of trehalose biosynthesis genes from
      hyperthermophilic archaebacterium Metallosphaera hakonesis.
AB  - The trehalose (alpha-D-glucopyranosyl-[1,1]-alpha-D-glucopyranose) biosynthesis
      genes MhMTS and MhMTH, encoding a maltooligosyltrehalose synthase (MhMTS) and a
      maltooligosyltrehalose trehalohydrolase (MhMTH), respectively, have been cloned
      from the hyperthermophilic archaebacterium Metallosphaera hakonesis. The ORF of
      MhMTS is 2,142 bp long, and encodes 713 amino acid residues constituting a 83.8
      kDa protein. MhMTH is 1,677 bp long, and encodes 558 amino acid residues
      constituting a 63.7 kDa protein. The deduced amino acid sequences of MhMTS and
      MhMTH contain four regions highly conserved for MTSs and three for MTHs that are
      known to constitute substrate-binding sites of starch-hydrolyzing enzymes.
      Recombinant proteins obtained by expressing the MhMTS and MhMTH genes in E. coli
      catalyzed a sequential reaction converting maltooligosaccharides to produce
      trehalose. Optimum pH of the MhMTS/MhMTH enzyme reaction was around 5.0 and
      optimum temperature was around 70 degrees C. Trehalose-producing activity of the
      MhMTS/ MhMTH was notably stable, retaining 80% of the activity after
      preincubation of the enzyme mixture at 70 degrees C for 48 h, but was gradually
      abolished by incubating at above 85 degrees C. Addition of thermostable 4-alpha
      glucanotransferase increased the yield of trehalose production from maltopentaose
      by 10%. The substrate specificity of the MhMTS/MhMTH-catalyzed reaction was
      extended to soluble starch, the most abundant maltodextrin in nature.

PMID- 18051365
TI  - Substitution of Pro206 and Ser86 residues in the retinal binding pocket of
      Anabaena sensory rhodopsin is not sufficient for proton pumping function.
AB  - Anabaena sensory rhodopsin is a seven transmembrane protein that uses all
      trans/13-cis retinal as a chromophore. About 22 residues in the retinal-binding
      pocket of microbial rhodopsins are conserved and important to control the quality
      of absorbing light and the function of ion transport or sensory transduction. The
      absorption maximum is 550 nm in the presence of all-trans retinal at dark. Here,
      we mutated Pro206 to Glu or Asp, of which the residue is conserved as Asp among
      all other microbial rhodopsins, and the absorption maximum and pKa of the proton
      acceptor group were measured by absorption spectroscopy at various pHs. Anabaena
      rhodopsin was expressed best in Escherichia coli in the absence of extra leader
      sequence when exogenous all-trans retinal was added. The wild-type Anabaena
      rhodopsin showed small absorption maximum changes between pH 4 and 11. In
      addition, Pro206Asp showed 46 nm blue-shift at pH 7.0. Pro206Glu or Asp may
      change the contribution to the electron distribution of the retinal that is
      involved in the major role of color tuning for this pigment. The critical residue
      Ser86 (Asp 96 position in bacteriorhodopsin: proton donor) for the pumping
      activity was replaced with Asp, but it did not change the proton pumping activity
      of Anabaena rhodopsin.

PMID- 18051366
TI  - The within-host population dynamics of normal flora in the presence of an
      invading pathogen and antibiotic treatments.
AB  - A mathematical competition model between normal flora and an invading pathogen
      was devised to allow analysis of bacterial infections in a host. The normal flora
      includes the various microorganisms that live on or within the host and act as a
      primary human immune system. Despite the important role of the normal flora, no
      mathematical study has been undertaken on models of the interaction between it
      and invading pathogens against a background of antibiotic treatment. To quantify
      key elements of bacterial behavior in a host, pairs of nonlinear differential
      equations were used to describe three categories of human health conditions,
      namely, healthy, latent infection, and active infection. In addition, a cutoff
      value was proposed to represent the minimum population level required for
      survival. The recovery of normal flora after antibiotic treatment was also
      included in the simulation because of its relation to human health recovery. The
      significance of each simulation parameter for the bacterial growth model was
      investigated. The devised simulation showed that bacterial proliferation rate,
      carrying capacity, initial population levels, and competition intensity have a
      significant effect on bacterial behavior. Consequently, a model was established
      to describe competition between normal flora and an infiltrating pathogen. Unlike
      other population models, the recovery process described by the devised model can
      describe the human health recovery mechanism.

PMID- 18051367
TI  - Expression profiles and pathway analysis in HEK 293 T cells overexpressing HIV-1
      Tat and nucleocapsid using cDNA microarray.
AB  - Human immunodeficiency virus type 1 (HIV-1) infections are responsible for a
      substantial number of deaths annually and represent a significant threat to
      public health. According to the latest study, the Tat (Transactivator of
      transcription) protein is essential in transcription and replication of viral
      genes, and is among the early expression genes involved in the life cycle of HIV.
      The virion NC (nucleocapsid) plays an important role in early mRNA expression and
      contributes to the rapid viral replication that occurs during HIV-1 infection.
      Therefore, we attempted to elucidate the relationship between the Tat protein and
      nucleocapsid protein. In a comparison of two independently prepared and
      hybridized samples, flag NC overexpressed HEK 293T cells and pTat overexpressed
      HEK 293T cells, and hybridization showed the differences in expression in each
      case. Among the microarray results confirmed with real-time reverse transcriptase
      assay, twelve genes were identified to be involved according to their gene
      expression profiles. Of approximately 8,208 human genes that were analyzed, we
      monitored candidate genes that might have been related to NC and Tat genes from
      gene expression profiles. Additionally, the pathways could be viewed and analyzed
      through the use of PathwayStudio software. The pathways from the gene list were
      built and paths were found among the molecules/cell objects/processes by the
      curation method.

PMID- 18051368
TI  - Construction of conjugative gene transfer system between E. coli and moderately
      thermophilic, extremely acidophilic Acidithiobacillus caldus MTH-04.
AB  - A genetic transfer system for introducing foreign genes to biomining
      microorganisms is urgently needed. Thus, a conjugative gene transfer system was
      investigated for a moderately thermophilic, extremely acidophilic biomining
      bacterium, Acidithiobacillus caldus MTH-04. The broad-host-range IncP plasmids
      RP4 and R68.45 were transferred directly into A. caldus MTH-04 from Escherichia
      coli by conjugation at relatively high frequencies. Additionally the broad-host
      range IncQ plasmids pJRD215, pVLT33, and pVLT35 were also transferred into A.
      caldus MTH-04 with the help of plasmid RP4 or strains with plasmid RP4 integrated
      into their chromosome, such as E. coli SM10. The Km(r) and Sm(r) selectable
      markers from these plasmids were successfully expressed in A. caldus MTH-04.
      Futhermore, the IncP and IncQ plasmids were transferred back into E. coli cells
      from A. caldus MTH-04, thereby confirming the initial transfer of these plasmids
      from E. coli to A. caldus MTH-04. All the IncP and IncQ plasmids studied were
      stable in A. caldus MTH-04. Consequently, this development of a conjugational
      system for A. caldus MTH-04 will greatly facilitate its genetic study.

PMID- 18051369
TI  - "Bring to lab" of 19 novel species among 60 isolates retrieved from a freshwater
      pond.
AB  - We report here on the cultivation of numerous novel bacterial species from a
      eutrophic freshwater pond. A total of 60 strains, 15 strains per each culture
      medium, were obtained from the surface of a eutrophic freshwater pond by
      employing a conventional dilution-plating method with four different kinds of
      culture media, including R2A, 1/10R2A, PCA, and 1/10PCA. Among the 60 strains
      isolated, 27 strains showed less than 97% 16S rRNA gene sequence similarities to
      validly published species, and thus they are considered to comprise 19 novel
      species. Of the 27 strains assigned to the novel species, the majority of the
      strains (20 strains) were affiliated with the Alphaproteobacteria and
      Betaproteobacteria. The remaining 7 strains were affiliated with the
      Gammaproteobacteria, Firmicutes, Actinobacteria, and Deinococci. Because we have
      isolated 19 novel species from a usual freshwater pond using a conventional
      culturing technique, our results suggest that an unexplored ecosystem, even if it
      looks like a common ecosystem found elsewhere, harbors diverse unidentified
      microbes, which will be definitely further characterized.

PMID- 18051370
TI  - Cadaverine protects Vibrio vulnificus from superoxide stress.
AB  - An electron paramagnetic resonance (EPR) signal characteristic of the 5,5'
      dimethyl-1-pyrroline-N-oxide (DMPO)-OH spin adduct, which is formed from the
      reaction of DMPO with superoxide radicals generated by xanthine oxidase-mediated
      reaction, was significantly reduced by the cadaverine or Escherichia coli Mn
      containing superoxide dismutase (MnSOD). Likewise, cytochrome c reduction by
      superoxide was inhibited by cadaverine, and the inhibition level increased in
      proportion to the level of cadaverine. The cadA mutant of Vibrio vulnificus,
      which does not produce cadaverine because of the lack of lysine decarboxylase,
      exhibits less tolerance to superoxide stress in comparison with wild type. The
      results indicate that cadaverine scavenges superoxide radicals, and protects
      cells from oxidative stress.

PMID- 18051371
TI  - R-type pyocin is required for competitive growth advantage between Pseudomonas
      aeruginosa strains.
AB  - R-type pyocin is a bacteriophage tail-shaped bacteriocin produced by Pseudomonas
      aeruginosa, but its physiological roles are relatively unknown. Here we describe
      a role of R-type pyocin in the competitive growth advantages between P.
      aeruginosa strains. Partial purification and gene disruption revealed that the
      major killing activity from the culture supernatant of PA14 is attributed to R
      type pyocin, neither F-type nor S-type pyocins. These findings may provide
      insight into the forces governing P. aeruginosa population dynamics to promote
      and maintain its biodiversity.

PMID- 18051372
TI  - [Chemical biology: overview].

PMID- 18051373
TI  - [Fluorescent probes to visualize only what we want to watch: measurements of
      reactive oxygen species, enzyme activity, and selenoproteins].

PMID- 18051374
TI  - [Detection of in-vivo free radical reaction using magnetic resonance].

PMID- 18051375
TI  - [Development of fluorescent probes for nitric oxide].

PMID- 18051376
TI  - [Mechanism-based molecular design of highly selective peroxynitrite probe].

PMID- 18051377
TI  - [Development of Zn2+ fluorescent probes for visualizing Zn2+ functions in
      neuronal system].

PMID- 18051379
TI  - [Chemistry in studies of fluorescent proteins].

PMID- 18051378
TI  - [Development of fluorescent probes for intracellular magnesium measurement and
      their applications to analysis of cellular mechanism].

PMID- 18051380
TI  - [Fluorescent bioimaging using degraton probes].

PMID- 18051381
TI  - [Imaging molecular processes in living cells].

PMID- 18051382
TI  - [HaloTag: a novel technology for in vivo bioimaging and protein functional
      analysis].

PMID- 18051383
TI  - [Fluorescent labeling of proteins by in-cell-directed chemistry].

PMID- 18051384
TI  - [Molecular design of hypoxic tumor cell-targeting drugs and imaging probes].

PMID- 18051385
TI  - [In-vivo cancer fluorescence imaging with novel precisely-designed fluorescence
      probes].

PMID- 18051386
TI  - [Fluorescent detection of protein kinase activity: methodology to visualize
      "phosphate"].

PMID- 18051387
TI  - [Fluorescent molecular thermometers for bioimaging].

PMID- 18051388
TI  - [Control of cellular microenvironment with a caged compound immobilized on a
      surface].

PMID- 18051389
TI  - [Bioprobe for imaging RNA in living cells].

PMID- 18051390
TI  - [Advanced fluorescence microscopes for future work].

PMID- 18051391
TI  - [Imaging and nano-manipulation of single biomolecules].

PMID- 18051392
TI  - [Strategy for chemical biology using affinity magnetic nanobeads].

PMID- 18051393
TI  - [Reprogramming the genetic code using flexizyme].

PMID- 18051394
TI  - [From systematic analysis of protein interaction networks to chemical-biology].

PMID- 18051395
TI  - [Synthesis of chemical probes based on combinatorial chemistry and lab
      automation].

PMID- 18051396
TI  - [Unelucidated biological phenomena].

PMID- 18051397
TI  - [Chemical biology of bioactive natural products controlling the rhythmic movement
      in plants].

PMID- 18051398
TI  - [Chemical factors depend on the density of organisms].

PMID- 18051399
TI  - [Mating behavior and pheromone production in moths].

PMID- 18051400
TI  - [Screening of bioactive metabolites that suppress inflammation].

PMID- 18051401
TI  - [Cancer cell informatics and chemical biology].

PMID- 18051402
TI  - [Peptide-lead drug discovery].

PMID- 18051403
TI  - [Protease inhibitors].

PMID- 18051404
TI  - [Kinase inhibitors].

PMID- 18051405
TI  - [Development of farnesyltransferase inhibitor for anti-cancer drugs].

PMID- 18051406
TI  - [Identification of target molecules for small-molecule inhibitors using yeast].

PMID- 18051407
TI  - [Biosynthesis of natural products from microbes].

PMID- 18051408
TI  - [Bioorganic chemistry of plant triterpene biosynthesis].

PMID- 18051409
TI  - [Biosynthesis of a hybrid terpenoid polyketide-derived natural product and
      production of useful prenylated compounds by using prenyltransferase].

PMID- 18051410
TI  - [Glycochemical biology].

PMID- 18051411
TI  - [Biological diversity of protein lysine acetylation which has been revealed by
      small molecule inhibitors].

PMID- 18051412
TI  - [New generation of Ca2+ indicators with greatly improved fluorescence
      properties].

PMID- 18051413
TI  - [Measurement of cytosolic free Ca2+ in individual small cells using fluorescence
      microscopy with dual excitation wavelengths].

PMID- 18051414
TI  - [Fluorescence ratio imaging of cyclic AMP in single cells].

PMID- 18051415
TI  - [Quantitation of transcription and clonal selection of single living cells with
      beta-lactamase as reporter].

PMID- 18051416
TI  - [Green fluorescent protein as a marker gene expression].

PMID- 18051417
TI  - [Crystal structure of the Aequorea victoria green fluorescent protein].

PMID- 18051418
TI  - [Fluorescent indicators for Ca2+ based on green fluorescent proteins and
      calmodulin].

PMID- 18051419
TI  - [Rapid photolytic release of adenosine 5'-triphosphate from a protected analogue:
      utilization by the Na:K pump of human red blood cell ghosts].

PMID- 18051420
TI  - [In-vivo imaging of tumors with protease activated near-infrared fluorescent
      probes].

PMID- 18051421
TI  - [In-vivo visualization of gene expression using magnetic resonance imaging].

PMID- 18051422
TI  - [Two-photon laser scanning fluorescence microscopy].

PMID- 18051423
TI  - [Engineering chemical reactivity on cell surfaces through oligosaccharide
      biosynthesis].

PMID- 18051424
TI  - [Identification of the cardiac beta-adrenergic receptor protein: solubilization
      and purification by affinity chromatography].

PMID- 18051425
TI  - [An approach to the targeted attachment of peptides and proteins to solid
      supports].

PMID- 18051426
TI  - [A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl
      isomerase].

PMID- 18051427
TI  - [Potent and specific inhibition of mammalian histone deacetylase both in vivo and
      in vitro by trichostatin A].

PMID- 18051428
TI  - [A mammalian histone deacetylase related to the yeast transcriptional regulator
      Rpd3p].

PMID- 18051429
TI  - [New type of synthetic peptide library for identifying ligand-binding activity].

PMID- 18051430
TI  - [Controlling signal transduction with synthetic ligands].

PMID- 18051431
TI  - [Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype
      based screen].

PMID- 18051432
TI  - [Synthetic small molecules that control stem cell fate].

PMID- 18051433
TI  - [Chemical switch for inhibitor-sensitive alleles of any protein kinase].

PMID- 18051434
TI  - [Synthesis of proteins by native chemical ligation].

PMID- 18051435
TI  - [Proteomic profiling of mechanistically distinct enzyme classes using a common
      chemotype].

PMID- 18051436
TI  - [Drug target validation and identification of secondary drug target effects using
      DNA microarrays].

PMID- 18051437
TI  - [Rapid identification of subtype-selected agonists of the somatostatin receptor
      through combinatorial chemistry].

PMID- 18051438
TI  - [Exploiting chemical libraries, structure, and genomics in the search for kinase
      inhibitors].

PMID- 18051439
TI  - [Role of LXRs in control of lipogenesis].

PMID- 18051441
TI  - [Discovering high-affinity ligands for proteins: SAR by NMR].

PMID- 18051440
TI  - [In-vivo activation of the p53 pathway by small-molecule antagonists of MDM2].

PMID- 18051442
TI  - [Mechanisms in the action of anesthetics].

PMID- 18051443
TI  - [Therapeutic angiogenesis using bone marrow cells].

PMID- 18051444
TI  - [Entity of TRALI and its therapeutic strategy].

PMID- 18051445
TI  - [General anesthesia/pain control in large and companion animals].

PMID- 18051446
TI  - [Neuronal regenerative medicine by using embryonic stem cells].

PMID- 18051447
TI  - [Clinical use of heart rate variability in the field of anesthesiology].

PMID- 18051448
TI  - [Mechanisms of surgical injury-induced pain].

PMID- 18051449
TI  - [Clinical electroencephalographic monitoring of depth of anesthesia].

PMID- 18051450
TI  - [Pathologic pain and vision are cross-modal].

PMID- 18051451
TI  - [Contribution of CB1 receptor in the DRG for nociception and its use for pain
      treatment].

PMID- 18051452
TI  - [Introduction: position of the research on anesthetic mechanisms from the
      anesthesiologist's perspectives].

PMID- 18051453
TI  - [Mechanisms of consciousness and anesthetic action explored by functional brain
      imaging].

PMID- 18051454
TI  - [Analysis of hypnotic or analgesic effect of anesthetic agents by in-vivo patch
      clamp recordings from somatosensory cortex in rats].

PMID- 18051455
TI  - [Role of presynaptic mechanisms in propofol-induced facilitation of gamma-amino
      butyric acid (GABA)-mediated inhibitory neurotransmission].

PMID- 18051456
TI  - [Approach to mechanism of general anesthesia from sleep physiology--from micro to
      macro].

PMID- 18051457
TI  - [Introduction: clinical aspects of spinal actions of anesthetic (anesthesia
      related) drugs].

PMID- 18051458
TI  - [Pain and glutamate receptors].

PMID- 18051459
TI  - [Function of spinal GABA receptor and its modulation].

PMID- 18051460
TI  - [Opioids and spinal analgesia].

PMID- 18051461
TI  - [Alpha2-adrenergic receptors in the dorsal horn of the spinal cord--their
      function and the descending inhibitory systems].

PMID- 18051462
TI  - [Prostaglandin and nociceptin/orphanin FQ].

PMID- 18051463
TI  - [Kampo medicine for the pain and the psychosomatic disorder--diagnosis and
      treatment].

PMID- 18051464
TI  - [Management of climacteric disturbance by Kampo medicine].

PMID- 18051465
TI  - [Clinical evaluation of Kampo medicine for the menopausal symptoms].

PMID- 18051466
TI  - [Application of herb medicine in pain clinic--focusing on the basic research of
      Aconiti tuber].

PMID- 18051467
TI  - [Addictive behavior disorders].
AB  - "Addiction" used to remind anyone of the use or abuse of chemical substances. In
      recent years, however, researchers and clinicians have begun to classify other
      excessive behaviors including gambling, eating shopping and self-injury into the
      addictive behavior. Above all, pathological gambling and bulimia nervosa patients
      often make trouble for psychiatrists and psychologists, not only for their
      family. On the other hand, the neural substrata underlying substance dependence
      have been revealed. Especially, it is implicated that the mesolimbic neuron plays
      a crucial role on the reward system. The recent studies suggest that reduced
      activation of the reward system might be related to the addictive behaviors such
      as pathological gambling, binge eating and sexual behavior. Further biological
      researches about the addictive behavior would help our deeper understanding of
      its disorders. As to the pharmacotherapy, many studies have demonstrated the
      efficacy of selective serotonin reuptake inhibitors (SSRIs) in treating the
      addictive behaviors.

PMID- 18051468
TI  - [Difference in mechanisms between psychological and physical dependence].

PMID- 18051469
TI  - [Development of a manualized cognitive behavioral therapy program for Japanese
      drug addicts and a study of the efficacy of the program].
AB  - In the West, various psychological programs have been developed to treat drug
      dependence. Although some programs have been performed as trials in a few
      facilities in Japan, there are no psychological treatment programs available in
      many facilities, and their effects on Japanese drug abusers have not been well
      studied. We developed a manualized cognitive behavior therapy (CBT) program for
      Japanese clients with drug dependence based on a review of the literature. The
      program focused on the development of relapse prevention skills through role
      playing, enhancement of motivation for recovery and self-care using relaxation
      technique. We studied the effects of the program for Japanese drug abusers. We
      evaluated the change after treatment, and compared findings between an
      intervention group and a control group. The results indicated that the program
      improved self-efficacies to cope with cravings and situations that increased the
      risk of relapse only in the intervention group, and physical complaints were
      decreased in the intervention group, although such complaints were increased in
      the control group. Seventy percent of the intervention group members indicated
      satisfaction and 50% indicated that the program was useful. These findings showed
      that the relapse prevention program was effective for Japanese clients. However,
      most emotional factors relevant to craving were not adequately changed in either
      group. We should improve the program, allowing the clients an opportunity to try
      the relapse prevention skills outside the facility and focus the emotion during a
      trial in vivo.

PMID- 18051471
TI  - [Space surgery].

PMID- 18051470
TI  - [A preliminary study on outpatient relapse prevention program for methamphetamine
      dependent patients: Serigaya Methamphetamine Relapse Prevention Program
      (SMARPP)].
AB  - Although methamphetamine use disorder has been prevalent in Japan for more than
      fifty years, there have been hardly any effective medical treatment modalities
      other than improving methamphetamine-induced psychosis through hospitalization
      and/or participation in self help groups and private rehabilitation centers. As
      such limited social resources for recovering methamphetamine dependents are
      insufficient to prevent patients from relapse, there are growing needs for
      developing effective outpatient treatment program based on a chronic care
      perspective. We have developed a relapse prevention program for Japanese
      methamphetamine abusers, modifying "Matrix" model and incorporating other
      treatment materials. Then a preliminary study on implementing the program was
      conducted in an outpatient setting at Kanagawa Psychiatric Center, Serigaya
      Hospital. Of sixty eight methamphetamine dependent patients who visited the
      hospital for the first time between September 2006 and February 2007, four agreed
      to participate in the study. The program was manual- and workbook-based, and we
      suggested participants to attend to the session three-times per week for two
      months. Also participants were asked randomly to turn in urine samples once a
      week. The participants consisted of a female and three males, with an average age
      of thirty. The length of abstinent period since the last use varied
      substantially, from five days to more than four years. Three had the experience
      of serving in prison for violating the Stimulant Drugs Control Law. The results
      of the present study were that all four completed the program, and presented with
      negative urine samples throughout the period. However, in terms of treatment
      retention, two out of the four dropped out of the outpatient treatment within a
      month after the program termination. These outcomes suggest that a relapse
      prevention program may successfully be provided for Japanese methamphetamine
      abusers in an outpatient setting, with a favorable, treatment retaining effect
      during the program period.

PMID- 18051473
TI  - [Trends in neonatal surgery in Japan].
AB  - A nationwide survey on neonatal surgery is conducted every five years by the
      Japanese Society of Pediatric Surgeons. The first survey was in 1964, and the
      most recent was in 2003. Three thousands seven hundreds and nine cases were
      collected in 2003. The number of newborns undergoing surgical management had
      increased substantially, in spite of a gradual decline in the annual birth rate
      for more than three decades. The overall mortality rate for newborns having
      surgery had improved to 9.0% in 2003, down from 32% in 1968. Intestinal
      perforations showed the worst mortality rate of 31.6%, probably due to an
      increment in the rate of low birth-weight babies. The mortality rate of Bochdalek
      hernias had been improving gradually and achieved 25.4%. Esophageal atresias and
      omphaloceles, which are frequently associated severe anomalies, had a mortality
      rate of more than 10%. The management of low birth-weight babies and of severe
      complicated anomalies should be improved.

PMID- 18051474
TI  - [Antenatal diagnosis of neonatal surgical diseases].
AB  - With advances in noninvasive fetal diagnostic tools, such as ultrasonography and
      magnetic resonance imaging, the percentage of neonatal surgical patients detected
      antenatally has increased. Recently, color Doppler as well as 3D imaging has
      contributed to more accurate diagnoses with ultrasonography. The significance of
      antenatal diagnosis for neonatal surgical disease and the current progress in
      fetal surgery are described and discussed. At present, congenital diaphragmatic
      hernia with extremely severe hypoplastic lung, congenital cystic adenomatoid
      malformation with hydrops, obstructive uropathy with oligohydramnios, and simple
      ovarian cyst greater than 5cm in diameter are considered to be appropriate
      indications for fetal surgery.

PMID- 18051475
TI  - [Current and future strategy in the treatment of congenital diaphragmatic
      hernia].
AB  - The severity of congenital diaphragmatic hernia (CDH) depends on the degree of
      lung hypoplasia. It is still difficult to rescue the most severely affected
      infants with cardiopulmonary insufficiency immediately after birth. However, the
      recent treatment strategy has improved the outcome of CDH. High-frequency
      ventilation (HFV) and gentle ventilation have been reported to be effective in
      the treatment of CDH by minimizing the barotrauma of the hypoplastic lung.
      Various vasodilators such as nitric oxide and prostaglandin-E1 have been found to
      be improve the pulmonary hypertension due to hypoplastic lung. On the other hand,
      the indications for extracorporeal membrane oxygenation (ECMO), which used to be
      the most powerful life support for severe CDH, have become limited. In our
      institute, antenatally diagnosed CDH infants with inadequate oxygenation despite
      maximum respiratory support immediately after birth are excluded from ECMO
      candidates because of fatal lung hypoplasia. Recently, it has been reported that
      temporary tracheal occlusion can accelerate fetal lung growth and improve the
      outcome of severe CDH. Percutaneous fetal endoluminal tracheal occlusion is
      expected to become an effective and minimally invasive treatment for fatal lung
      hypoplasia due to CDH.

PMID- 18051476
TI  - [Present and future treatment of esophageal atresia].
AB  - There has been steady improvement in the overall survival rate of patients with
      esophageal atresia during the past 30 years. With modern neonatal intensive care,
      very low birth-weight infants with esophageal atresia are also expected to
      survive. However, there are many questions in the treatment including delayed
      primary surgery and multistaged esophageal elongation for extremely low birth
      weight infants and patients with long-gap esophageal atresia, respectively. On
      the other hand, reports of thoracoscopic repair of esophageal atresia are
      increasing, although there has been no report on long-term follow-up. This
      procedure has many advantages including wound cosmesis and little thoracic
      deformity, but it is technically difficult even for experienced endoscopic
      surgeons and is performed only in a few children's hospital in Japan. Easier
      thoracoscopic surgery using robotic technology is expected in the near future.

PMID- 18051477
TI  - [Bowel perforation in the newborn baby].
AB  - The pattern of neonatal gastrointestinal perforation has changed with the
      previous high frequency of gastric rupture being replaced by necrotizing
      enterocolitis (NEC) in recent years. NEC has become the most common cause of
      gastrointestinal perforation resulting in a surgical emergency in the Neonatal
      Intensive Care Unit (NICU). Over the last 20 years, the infant mortality rate
      attributable to NEC has not decreased. However, in our institutions, more than
      70% of babies with NEC are premature infants weighing less than 1,000g, which is
      one of the main reasons why the mortality rate due to neonatal gastrointestinal
      perforation has not improved in recent years. NEC totalis or massive necrosis of
      nearly all of the intestine is uniformly fatal. Limited resection followed by
      second-look laparotomy after abdominal drainage is one method used to limit the
      length of intestinal resection but most of these infants died from sepsis with
      cardiovascular collapse and multisystem organ failure. Among extremely low birth
      weight infants surviving after NEC significant growth delay and adverse
      neurodevelopmental outcome are common sequelae. More recently, many extremely low
      birth-weight infants are commenced on early low-volume feeds of breast milk or
      probiotics. This appears to be reducing the incidence of NEC and may explain a
      drop in the mortality rate over the last five years.

PMID- 18051478
TI  - [Recent development of congenital heart surgery in neonates and small infants].
AB  - Cardiac surgery has been developed dramatically during these 50 years since Gross
      and Lellihei pioneered repair of intracardiac anomalies using cardiopulmonary
      bypass in mid 1950's. In late 1960's and early 1970's, the technique of deep
      hypothermia and circulatory arrest (DHCA) has been developed in Japan and Sir
      Brian Barratt-Boyes in New Zealand used Kyoto technique (DHCA) to repair many
      infants and small children with complex congenital heart diseases (CHD). The
      introduction of DHCA was an important development in the history of the treatment
      of CHD, allowing the approach of previously unrepairable lesions. Open heart
      surgery in neonates has been adopted worldwide since Castaneda in Boston
      performed neonatal arterial switch in mid 1980's. Since then, most of our efforts
      have been led to repair most of the CHD primarily in neonate and small infants.
      Mortality of open heart surgery in neonates has dropped significantly during
      recent 10 years and now, more than 95% of the children with CHD survive in Japan.
      Surgical strategies and results in each CHD were summarized.

PMID- 18051479
TI  - [The actual situation of MDRP infections].

PMID- 18051480
TI  - [What we can learn from a case of medical malpractice--cases of a central venous
      hyperalimentation catheter breaking on attempted removal leaving the end of the
      catheter in the heart].

PMID- 18051481
TI  - [Surgery for atrial fibrillation].

PMID- 18051482
TI  - [Modular organization of a teaching process in the postgraduate training of
      physicians].

PMID- 18051483
TI  - [European Foundation for Education in Anesthesiology (FEEA): the first steps in
      Russia].
AB  - The mission, structure, and working schedule of the Foundation for European
      Education in Anesthesiology (FEEA), an international non-profitable organization
      with 70 centers being located in Europe, Central and South Americas, Africa, and
      Asia, are described in the article. The first FEEA seminars in Russia were
      organized in St. Petersburg in 2006-2007 by the Association and Society of
      Anesthesiologists and by all the anesthesiology departments of the city. Today's
      geography of FEEA seminars dedicated to European Society of Anesthesiology
      diploma exam training is expanding in Russia.

PMID- 18051484
TI  - [Extramural training of medical students in the area "anesthesiology and
      reanimatology"].

PMID- 18051485
TI  - [Training of anesthesiology-resuscitations physicians in clinical residency:
      resident's experience].
AB  - An educational process in clinical residency is discussed in terms of the results
      of anonymous questionnaire survey: the respondents were 77 residents in
      anesthesiology. A significant proportion (28%) of the trainees felt knowledge
      shortage and even more (47%) were diffirent in their own professional future.
      There were serious problems regarding practical training organization. Half of
      the trainees pointed out patients' inaccessibility. In the residents' opinion,
      the best clinical teacher is a staff anesthetist (42%) or assistant professor
      (39%). The vast majority (84%) of the trainees believe that one tutor should
      teach more than two trainees. The ways of solving these or those problems in
      clinical residency training and the prospects for primary postgraduate education
      in anesthesiology are discussed.

PMID- 18051486
TI  - [Informational needs of anesthesiologists and their address satisfaction in the
      postgraduate training system].
AB  - Large-scale questionnaire survey of anesthesiologists, the attendees of advanced
      training courses, showed the rating of the most important applied topics. Of
      paramount value appeared to be issues devoted to respiratory support and
      monitoring. Every third respondent reported the importance of applied
      psychological training for anesthetists. Moreover, a list of topics the attendees
      should like to listen to, but they had not obtained necessary information was
      compiled. Among these topics, these included applied intensive care, the legal
      aspects of the specialty, etc. Knowledge of the current informational needs of
      attendees is required for the effective operation of postgraduate education.

PMID- 18051487
TI  - [Mechanisms of psychological adaptation of anesthesiologists-resuscitators to the
      stress-induced conditions of professional occupation and possibilities of their
      correction within a teaching process].
AB  - High psychological tension results in the development of specific coping
      behavior. Ninety-six anesthesiologists, including 62 (64.6%) males and 34 (35.4%)
      females, were examined to reveal the mechanisms of psychological adaptation to
      stress-induced conditions of professional occupation. The respondents were
      ascertained to most frequently use cognitive, emotional, and behavioral
      constructive copings in settling stress situations. Nonadaptive copings most
      commonly contemplate a refusal to get over difficulties due to the lack of faith
      in power, to the underestimation of the importance of negative events, to
      passivity, isolation, etc., which is traditionally considered to be a
      manifestation of the emotional burnout syndrome in attendants. Psychological
      training within a teaching process may be regarded as a help to physicians in
      developing constructive coping strategies, training in self-diagnosis and self
      help in the early manifestations of emotional burnout.

PMID- 18051488
TI  - [Quality assurance of the therapy of patients in the department of anesthesiology
      and intensive care].
AB  - Emphasis is laid on the fact that the normative legal basis of an
      anesthesiological-resuscitative service is contrary to the real conditions of its
      operation at the present stage. Data on the age-sex and nosological structures of
      patients treated at an intensive care unit of a large multidisciplinary hospital,
      the scope of their examination and treatment, and the results of work time
      keeping in the employees of the unit are given. The authors' proposals to improve
      the organization of service work and to upgrade its quality are presented in
      conclusion.

PMID- 18051489
TI  - [The cardiac performance recovery pattern and central hemodynamics in patients
      with coronary heart disease during coronary bypass surgery under extracorporeal
      circulation].
AB  - Central hemodynamic parameters were retrospectively studied in 284 patients.
      After aortic declamping, sinus rhythm spontaneously restored in 179 patients
      (Group 1), ventricular fibrillation occurred in 105 (Group 2). The preoperative
      parameters were similar in both groups. The number of grafts and the time of
      aortic clamping and cardiopulmonary bypass (CPB) were higher in Group 1. In the
      groups, the volume of cardioplegic solution and the average dose of phenylephrine
      and nitroglycerin per perfusion did not differ. After CPB, the values of cardiac
      output (CO) and cardiac index (CI) were significantly higher in Group 1 than in
      Group 2. At the end of an operation and 3 hours after its termination, there were
      no differences between two groups. Twelve hours after surgery, cardiac output and
      systolic blood pressure were significantly higher in Group 1. Following 24 hours
      of surgery, heart rate was significantly greater in Group 1 than in Group 2 After
      surgery, all hemodynamic parameters were within normal physiological values. The
      mean duration and the degree of inotropic support did not differ in the groups.
      The incidence of atrial fibrillation, perioperative myocardial infarction, and
      low cardiac output syndrome were comparable in both groups. Thus, various modes
      of cardiac performance recovery affect perioperative hemodynamics; however, this
      impact is insignificant and does not make management policy be changed in such
      patients. After aortic declamping, ventricular fibrillation requiring for
      defibrillation is not a clinical sensitive factor that negatively affects the
      intra- and postoperative period.

PMID- 18051490
TI  - [Risk factors of prolonged intensive care after early activation of
      cardiosurgical patients].
AB  - The purpose of the study was to reveal the predictors of more than 24-hour
      intensive care unit stay for patients activated early (up to 5 hours) after
      surgery under extracorporeal circulation and to explore the possibilities of
      predicting the prolongation of postoperative intensive care in the clinical
      situation under examination. The protocols of anesthetic maintenance, early
      activation, and postoperative intensive care were analyzed in 83 patients (50
      males and 33 females) aged 31 to 82 years, who had been operated on under
      extracorporeal circulation for various cardiosurgical diseases. The multiple
      regression analysis showed that the significant predictors of more prolonged
      intensive care after early activation were the level of arterial lactatemia (p =
      0.0021), the dosages of adrenaline and/or noradrenaline (p = 0.0048), age (p =
      0.0051), and female sex (p = 0.0142). It was shown that the multiple regression
      analysis could approximately predict the duration of intensive care after early
      activation. The predicted and actual durations of intensive care in patients with
      an intensive care unit stay length of more than 24 hours coincided in 52% of
      cases. In patients with an intensive care unit stay length of less than 24 hours,
      the estimated and actual durations of intensive care were in agreement in 92% of
      cases. It is concluded that it is expedient to take into account the results of
      the performed analysis in choosing the optimum postoperative management policy in
      cardiosurgical patients who are to undergo early activation.

PMID- 18051491
TI  - [Efficiency of preemptive intravenous paracetamol analgesia in abdominal
      surgery].
AB  - In a randomized, controlled study, 50 patients underwent elective surgery for
      abdominal cancer lesions under perioperative epidural analgesia. All the patients
      were randomized to receive paracetamol in a single intravenous dose of 1 g or
      placebo 30 minutes prior to the start of surgery. The use of 1 g of paracetamol
      as a single intravenous preemptive dose in abdominal surgery with perioperative
      epidural analgesia does not reduce the consumption of the analgesic and the
      intensity of pain in the postoperative period.

PMID- 18051492
TI  - [Oxidative stress and hepatic monooxygenase function in patients with coronary
      heart disease before and after cardiac surgery].
AB  - The parameters of lipid peroxidation (LPO) and hepatic monooxygenase function
      (HMF) were studied in 92 patients with coronary heart disease (CHD). After
      termination of and within the first 24 hours after myocardial revascularization,
      the levels of malonic dialdehyde and conjugate trienes were found to show 45.6
      and 62.1% increases, respectively. The half-life of antipyrine (AP T(1/2))
      increased by 23.5%. Studies on postoperative days 3-4 and 10-12 revealed a
      reduction in LPO rates and normalized HMF. After off-pump surgery, LPO and HMF
      significantly unchanged. On the contrary, open heart surgery resulted in a
      noticeable activation of LPO and an almost 1.5-fold decrease in HMF. The increase
      in oxidative stress and the deceleration of hepatic microsomal oxidation were
      ascertained to be directly related to the duration of extracorporeal circulation
      and the time of myocardial ischemia. After surgery, the rate of LPO and the
      reduction of HMF were more considerable in patients with multiple organ
      dysfunctions, as compared with the uncomplicated postoperative period. Within the
      first 24 hours following surgery, AP T(1/2) increased by 83.4%, but on
      postoperative days 10 to 14, it remained to be decreased by almost 1.5 times as
      compared with the baseline. Thus, LPO activation is one of the leading mechanisms
      of decelerated hepatic xenobiotic biotransformation after myocardial
      revascularization. Diminished lower HMF enhances the sensitivity of CHD patients
      to drug therapy and requires a differential approach to its use.

PMID- 18051493
TI  - [Does nitroglycerin show the properties of a selective venodilator?].
AB  - The central hemodynamic effect of continuous intravenous nitroglycerin infusion
      at an increasing rate (0.01-0.1 microg x kg(-1) x min(-1)) was evaluated by
      noninvasive (tetrapolar rheography) and invasive (pulmonary arterial
      catheterization) techniques. The study included 10 healthy volunteers and 30
      patients having usual indications for nitroglycerin infusion. The findings
      suggest that when even infused at low rates, nitroglycerin canses mainly
      arteriolar vasodilatation, which appears as increased stroke volume due to the
      predominance of diminished postload over lowered preload. It is obvious that the
      notion of nitroglycerin as a selective venodilator should be revised.

PMID- 18051494
TI  - [Efficiency of antioxidative therapy for acute poisoning by cautery substances].
AB  - Analysis of the clinical and laboratory parameters in patients with acute
      poisoning by cauterants has demonstrated that inclusion of the antioxidant
      mexidole into the package of therapeutic measures is effective in treating the
      above pathology. This is supported by the reductions in the proportion of fatal
      outcomes by more than twice and in the incidence of pneumonia complicating the
      course of the underlying disease, as well as by the increase in the rate of
      regeneration of ulceronecrotic defects in the gastrointestinal tract and by the
      decrease in the number of gastric cicatricial deformities when mexidole is
      locally used.

PMID- 18051495
TI  - [Noninvasive cardiac output determinations].
AB  - The thermodilution determination of cardiac output (CO) by pulmonary arterial
      catheterization is considered to be the gold standard. However, a diversity of
      complications associated with the insertion and use of a catheter has made for
      the design of CO-measuring devices in a mini- or noninvasive mode. This
      prospective controlled study has been conducted to compare various CO
      determination techniques by the shape of the arterial curve (ART), as shown by
      the use of a transesophageal Doppler ultrasonic sensor (TEDUS) determining the
      blood flow velocity in the descending thoracic aorta by the Fick's backward
      equation with partial CO2 recirculation, by measuring thoracic bioimpedance
      (Tbio) by bolus thermodilution as the reference method (CO BT). In all the study
      examined, the mean CO values are lower than those in the reference method. In
      addition, there was a wide scatter of the CO values calculated by alternative
      methods. The mean difference and its standard deviation are 1.27 +/- 2.26 (ART);
      0.87 +/- 1.57 (TEDUS); 1.01 +/- 1.46 (Fick); and 1.46 +/- 1.70 (Tbio). The errors
      of the methods, as compared to CO BT have the following values: APT, 27% (24-31%
      conference interval (CI)); TEDUS, 19% (17-21% CI); Fick, 20% (19-22%); Tbio, 25%
      (22-27%). By taking into account the findings, it should be stated that there is
      not any accurate mini- or noninvasive CO determination method that could
      completely substitute for the classical thermodilution technique.

PMID- 18051497
TI  - [Regional anesthesia: combined spinal epidural anesthesia].
AB  - The review deals with the promising method of regional anesthesia--combined
      epidural anesthesia. It gives indications for anesthesia, the specific features
      of its technical performance, and possible complications.

PMID- 18051496
TI  - [Comparison of cardiac output measurements by six different methods before and
      after extracorporeal circulation].

PMID- 18051498
TI  - [Therapy for chronic pain: historic experience and prospects].

PMID- 18051499
TI  - [Study on the THz spectra of tyrosine].
AB  - Terahertz time-domain spectroscopy (TDS) has been used to study the spectral
      properties of tyrosine at room temperature. The terahertz spectra of sample were
      observed. The result shows that the sample has the spectral response in terahertz
      spectral range, a fact demonstrating that the terahertz spectra of tyrosine could
      be used to study the molecular structure and vibration of sample. Two absorption
      peaks were found at 0.23 and 2.46 THz respectively for the first time. The
      corresponding theoretical spectra were given by using HF and DFT methods for both
      tyrosine monomer and dimmer. The difference between the theoretical and
      experimental results was analyzed in detail. The origin of the observed
      absorption at 0.23 THz was assigned to the wagging of the two tyrosine molecules
      linked by hydrogen bond.

PMID- 18051500
TI  - [Using the statistic preprocessing method to raise the measurement accuracy of
      dynamic spectrum].
AB  - The development of the non-invasive measurement of blood compositions by near
      infrared spectroscopy has attracted significant interests in recent years. But it
      has not yet been applied to the clinical field except the oximeter. The most
      important and difficult problem is that the instrument accuracy does not meet the
      requirement of the non-invasive measurement of blood compositions due to the
      effect of the individual discrepancy and complicated measurement conditions. So
      how to reach the instrument accuracy required is its key part. Based on the
      dynamic spectroscopy, a new non-invasive measurement method of blood compositions
      is presented, where the measurement accuracy is raised through the outlier
      eliminating and the assembly average of several measurement results. It has been
      proved by the experiment that the measurement accuracy can be raised by the
      outlier eliminating and the assembly average of several measurement results.

PMID- 18051501
TI  - [Study of thermal diffusivity by piezoelectric photoacoustic phase].
AB  - Piezoelectric photoacoustic phase information can be applied to determine the
      thermal diffusivity of sample. In actual experiments, the results of phase versus
      modulation frequency deviate from the theory heavily because of the disturbance
      of instrumental contribution from the whole detecting system. Considering that
      the instrumental contribution of phase from PA cell can be ignored reasonably,
      there will be no additional phase contribution after the piezoelectric PA cell
      has been replaced by microphone PA cell while the other experimental conditions
      have been kept invariable. Based on this hypothesis, the conventional
      photoacoustic cell with microphone is employed to determine the instrumental
      contribution of whole detecting system by studying the PA phase of solid rare
      earth complexes. The instrumental contribution of phase was considered to be
      constant for that the same detecting system was used in both the microphone PA
      method and piezoelectric PA method. This method has been proved by detecting the
      thermal diffusivity of aluminium sample. The corrected results of experiments
      match the theory well, showing that the method of subtracting the instrumental
      contribution from the original experimental phase can be applied reasonably in
      relevant chopping frequency region. While in lower chopping frequency region,
      there will be a little deviation from the theoretical results. The method has
      been also employed to the photoacoustic detection of leaf, and the thermal
      diffusivity of leaf can be acquired by studying the piezoelectric photoacoustic
      phase.

PMID- 18051502
TI  - [Calibration of the detection performance for hyperspectral imager].
AB  - As an image-spectrum merging technology, hyperspectral imaging has been used in
      battlefield reconnaissance rapidly. The calibration of hyperspectral imager is a
      process that corrects itself's output. An UV/Vis/NIR hyperspectral military
      detection system based on BTCCD and concave grating parts is analyzed, and it's
      spectral resolution is 3.3 nm. Some calibration and evaluation methods are
      discussed for hyperspectral imaging system which operates at 0.25-1.1 mm
      waveband. Image quality assessment based on an uniform radiation source with
      target, spectral quality assessment based on laser and Hg lamp, and radiation
      performance calibration based on high accuracy standard are researched
      detailedly. After several steps of radiation calibration and spectral fidelity
      verification, the reflective curve which represents the objective spectral
      character was obtained, satisfying the requirement of 0.2 mrad spatial resolution
      and +/-0.5% dispersive linearity. Finally, satisfactory results were obtained
      with these methods in a military detection system.

PMID- 18051503
TI  - [Study on the emission spectra of N2 plasma jet by AC glow discharge].
AB  - N2 plasma jet was generated from a nozzle using an AC discharge at about 15 kV.
      The emission spectra were obtained by using the concentration modulation
      spectroscopic technique. The dependence of spectral signal on the discharge
      current was discussed. It was found that the vibrational temperature decreased
      first and then increased downstream from the nozzle by measuring the emission
      spectra from different axial positions in the jet. A phenomenological model was
      presented to explain the vibrational temperature variation with different axial
      position z. The N2+/N2 ratio varied along the axis and the property of discharge
      in the experimental system was studied.

PMID- 18051504
TI  - [Spectrum analysis of modulated polarized light in phase retardation
      measurement].
AB  - The fundamental principle of light modulation is presented. The characteristic of
      light modulator is discussed both in time and frequency domains. Fourier
      transform spectrum of the intensity shows that the intensity distribution of
      outgoing light is the superposition of a series of Dirac functions in the
      frequency domain. The corresponding intensity distribution curves are also
      presented. A novel method for phase retardation measurement based on modulated
      polarized light is introduced. The spectrum analysis indicates that the perfect
      compensation condition can be satisfied only when the odd frequency components
      disappear. Under this condition, the phase retardation to be detected can be
      directly obtained from the compensation quantity of the compensator. This method
      is a direct measurement which is clearly superior to those indirect methods,
      especially in terms of high accuracy and low error. Based on the theoretical
      analysis, relevant experiments were conducted. And experimental results with high
      precision were obtained.

PMID- 18051505
TI  - [Investigation of optical and EPR spectra of ZnO : V3+ crystal].
AB  - In the present paper, the 45 X 45 energy matrix of the 3d2 ions in trigonal
      symmetry with the strong-field-coupling mechanism is established. The forty-five
      optical energy levels and five EPR parameters (including the zero-field splitting
      D, g factors g//, g perpendicular and hyperfine structure constants A//, A
      perpendicular) of ZnO : V3+ cryst are calculated from the diagonalization of this
      complete energy matrix. The calculated results are in agreement with the observed
      values. Based on the calculation, it was found that the local structure of V3+
      impurity center is different from the corresponding structure in the host
      crystal, i. e., the V3+ ion in ZnO does not occupy the exact Zn2+ site, but is
      displaced by DeltaZ approximately 0.003 nm along the c3 axis. The reasonableness
      of these results is discussed.

PMID- 18051506
TI  - [The inspection of amoxicillin medicines studied by the terahertz time-domain
      spectroscopy technique].
AB  - The amoxicillin medicines are widely used in the clinical medicine and ordinary
      life. The inspection of them is vitally important to the health of the patients
      and the protection of the legal manufactures. Terahertz is a newly developed
      electromagnetic radiation with many characteristic properties. In the present
      paper, three amoxicillin capsules produced by three different companies were
      studied by the terahertz time-domain spectroscopy technique. The time-domain
      spectra and the frequency-domain spectra were obtained, and consequently both the
      absorption coefficient and the refraction index were calculated. The results
      indicated that the absorption coefficient of the three samples were almost the
      same, while the refractive indexes of them were different to some extent. It is
      suggested that the terahertz time-domain spectroscopy is a powerful candidate
      technique in the quality inspection of penicillin medicines and the crackdowr on
      the fake drugs.

PMID- 18051507
TI  - [Spectrum study on highly saturated blue organic top-emitting devices with
      microcavity structure].
AB  - The blue top-emitting organic light-emitting devices with cavity effect have been
      fabricated. The authors used the TBADN : 3% DSAPh as emitting material of blue
      microcavity OLEDs. The devices consisted of Ag/ITO/CuPc/NPB/TBADN : 3%
      DSAPh/Alq3/LiF/Al(Ag) structure. On a patterned glass substrate, silver was
      deposited as reflective anode, and copper phthalocyanine (CuPc) layer as HIL and
      4'-bis[N-(1-Naphthyl)-N-phenyl-amino] biphenyl (NPB) layer as HTL were made.
      Aluminum and silver thin films were made as semi-transparent cathode. The
      transmittance of aluminum and silver (Al/Ag) cathode was about 30%. In EL
      spectrum, the full width at half maximum (FWHM) was only 17 nm. By changing the
      thicknesses of ITO, highly saturated color with Commission Internationale de
      L'Eclairage chromaticity coordinates (CIEx,y) of (0.141, 0.049) was obtained. In
      the present article, the emission intensity of spectrum was studied. An
      appropriate cathode transmittance will result in maximal emission intensity. By
      using the formula of microcavity, the approximative curve that describes the
      change of emission intensity with cathode transmittance (or reflectance) was
      figured out.

PMID- 18051508
TI  - [Influence of sample surface roughness on mathematical model of NIR quantitative
      analysis of wood density].
AB  - Near infrared spectroscopy is widely used as a quantitative method, and the main
      multivariate techniques consist of regression methods used to build prediction
      models, however, the accuracy of analysis results will be affected by many
      factors. In the present paper, the influence of different sample roughness on the
      mathematical model of NIR quantitative analysis of wood density was studied. The
      result of experiments showed that if the roughness of predicted samples was
      consistent with that of calibrated samples, the result was good, otherwise the
      error would be much higher. The roughness-mixed model was more flexible and
      adaptable to different sample roughness. The prediction ability of the roughness
      mixed model was much better than that of the single-roughness model.

PMID- 18051509
TI  - [Application study of ant colony algorithm in near infrared spectroscopy
      quantitative analysis].
AB  - Ant colony algorithm is a novel bio-inspired optimization algorithm, which
      simulates the foraging behavior of ants for solving various complex combinatorial
      optimization problems. The advantages of ant colony algorithm are intelligent
      search, global optimization, robustness, distributed computation and easy
      combination with other heuristic method. Near infrared spectroscopy quantitative
      analysis has been applied in many fields, whereas the key step is building the
      calibration model of measured data. In the present paper, ant colony algorithm
      was used to build the quantitative analysis model of Fourier transform near
      infrared diffuse spectroscopy for protein in cereal. Satisfied results were
      obtained. For calibration set, the correlation coefficient and relative standard
      deviation were 0.943 and 3.41%, respectively, while for prediction set, the
      correlation coefficient and relative standard deviation were 0.913 and 4.67%,
      respectively.

PMID- 18051510
TI  - [Application of FTIR array of correlation coefficient to the identification of
      Salvia miltiorrhizae Bge].
AB  - Based on the fingerprint infrared spectrum database, array of correlation
      coefficient has been first applied to identify traditional Chinese medicine
      slviae miltiorrhizae Bge. from different producing areas and growing
      environments. The result showed that the setting of high correlation coefficient
      in particular ranges of spectrum could differentiate the producing area of
      Slviae, while the setting of low correlation coefficient threshold of R5 to R7
      ranges could identify wild or cultivated samples. This approach seems to be not
      only a simple but also an accurate method for identifying the character of
      different Slviae.

PMID- 18051511
TI  - [FTIR spectroscopy analysis of mosses with different kinds of peristomes and its
      systematic significance].
AB  - The spectra of 23 species of mosses belonging to different kinds of peristomes
      were determined by Fourier transform infrared (FTIR) spectroscopy. Based on
      comparing the differences in the spectra of five representative species, four
      ranges of 1790-1330 cm(-1), 1200-960 cm(-1), 895-830 cm(-1) and 725-655 cm(-1)
      were selected as the characteristic spectra for analysis. The results show that
      hierarchical cluster analysis (HCA) and principal components analysis (PCA) using
      the second derivatives FTIR spectra can effectively identify five kinds of
      mosses: Sphagnidae, Nematodontae, Acrocarpi-Haplolepideae, Acrocarpi
      Diplolepideae, and Pleurocarpi-Diplolepideae, which are well suited for the known
      moss systems based on peristome structure. Therefore, FTIR spectra combined with
      chemometrics can be used as a useful tool in systematic research on bryophytes.

PMID- 18051512
TI  - [Theoretical study on infrared vibration spectrum of (SiO2)nO2H4].
AB  - Infrared vibration spectra of nanosize (SiO2)n,O2H4 with line, ring and cage
      structures were calculated using the density-functional theory (B3LYP) at 6
      31G(d) level. For quasi 1D (one dimension) line and ring structure, the
      frequencies of stronger infrared vibration modes monotonically change as a
      function of the length, which shows strong size effect. The IR vibration modes in
      directions parallel and perpendicular to the axis of nanoline or nanoring have
      opposite size dependence trends, showing the real vibration anisotropy property
      of nano scale material. Due to constructional complexity, cage structure does not
      have quasi 1D character. Morever, IR vibration modes increase as structural
      symmetry decreases. Vibrations of two-membered ring, isolated hydroxyls of three
      structures and framework SiO4 tetrahedron in cage structure agree well with
      experimental data. Theoretical calculation result of IR spectra can be used to
      guide characterization of silicon oxide nano scale materials fabricated in
      experiment.

PMID- 18051513
TI  - [Study on identification of Gastrodia elata Bl. by Fourier self-deconvolution
      infrared spectroscopy].
AB  - In the present article the FTIR spectra of the wild and planting Gastrodia elata
      Bl. from different habitats and its confusable varieties such as Canna edulis Ker
      Gawl, Colocasia esculenta (L.) Schott and Solanum tuberosum L. were obtained by
      horizontal attenuated total reflection infrared spectroscopy (HATR-FTIR), and
      were all transformed by Fourier self-deconvolution. The authors investigated the
      discrepancy extent of Fourier self-deconvolution of Gastrodia elata Bl and
      confusable varieties under various bandwidth and enhancement, and found that the
      discrepancy extent of Gastrodia elata Bl and confusable varieties was the most
      obvious when the bandwidth was between 75.0 and 76.0 and enhancement was 3.2. By
      adopting Fourier self-deconvolution infrared spectroscopy (FSD-IR) analytical
      method the samples were studied in detail. The results showed that we could find
      out the difference among them by means of Fourier self-deconvolution infrared
      spectroscopy, although it was very difficult to find out the difference in FSD-IR
      spectra of wild and planting Gastrodia elata Bl., and asexual reproduction and
      sexual reproduction Gastrodia elata Bl. The difference in FSD-IR spectra between
      Gastrodia elata Bl. and its confusable varieties is also very great. Therefore,
      this method can be used to recognize different Gastrodia elata Bl. and its
      confusable varieties simply, rapidly and accurately.

PMID- 18051514
TI  - [Analysis and identification of sea cucumber and products].
AB  - As high-grade health foods, the deep-processed products of sea cucumber, such as
      its capsule, injection and etc, have a broad prospect. But so far there is not a
      generalized efficient verification method or standard for these products. In this
      research, the authors used Fourier transform infrared spectroscopy (FTIR) and two
      dimensional correlation infrared spectroscopy (2D-IR) to determine fine sea
      cucumber products. At first, by processing live sea cucumber, the authors got
      some standard spectra. Then the authors used them to compare with different kinds
      of products, from the correlation coefficient of which the authors found the sea
      cucumber capsule made by Hai-Yan-Tang Corp. the most correlative with ours. This
      indicates that the capsule is filled with pure sea cucumber powder and has high
      quality. The authors' research also implies that the quality-verification for sea
      cucumber products by using a database of their standard spectra is quite
      possible.

PMID- 18051515
TI  - [Estimation of soluble solids content of intact citrus fruit by Vis/NIR
      spectroscopy].
AB  - Visible/Near-infrared (Vis/NIR) spectroscopy has become a very popular technique
      for the non-invasive assessment of intact fruit. The feasibility of using Vis/NIR
      spectroscopic technology for rapid quantifying soluble solids content (SSC) of
      citrus fruit was investigated by means of spectral transmittance mode. A total of
      110 citrus fruit samples were used to develop the calibration and prediction
      models. The relationship between actual SSC and Vis/NIRS spectra of citrus fruit
      samples was analyzed via pricipal component regression (PCR) and partial least
      squares (PLS) regression method using TQ 6.2 spectral analysis software. Models
      based on the different spectral pre-processing methods were compared in the
      present research. Performance of different models was assessed in terms of root
      mean square errors of prediction (RMSEP) and correlation coefficients (r2) of
      prediction set of samples. The best predictive models feature a RMSEP of 0.538%
      and correlation coefficient (r2) of 0.801 for SSC. The results show that the
      Vis/NIR transmittance technique is a feasible, accurate and fast method for non
      invasive estimation of citrus fruit SSC.

PMID- 18051516
TI  - [Study on the relationship between spectral properties of oilseed rape leaves and
      their chlorophyll content].
AB  - Chlorophyll is the important factors of the crop in its growth stage, and it is
      the favorable indicator of nutrition stress and photosynthesis. Site-specific
      crop nutrition diagnosis is the basics of the scientific fertilizer management,
      and it is essential for the practice of precision agriculture. Spectral
      properties of the oilseed rape leaves in different nitrogenous fertilizer levels
      were measured using visible-near infrared reflectance spectroscopy (Vis-NIRS)
      with natural illumination in the present study. According to the unique spectral
      properties of the crop, multiple stepwise regression technique was used to find
      the relationships between chlorophyll content and red edge, green edge. The
      result shows that the model with two independent variables (red edge, green edge)
      was better than with the one independeot variable (red edge). The correlation
      coefficient was 0.863, 0.848, and SEC was 5.273, 5.459, respectively. It can be
      seen the combination of the red edge and green edge can accurately predict
      chlorophyll content.

PMID- 18051517
TI  - [Study on quality detection of milk powder based on near infrared spectroscopy
      (NIR)].
AB  - The traditional NIR model was usually built according to various parameters of an
      individual type of milk powder so that it's really time-consuming. To simplify
      the application of NIR in real-time quality detection of milk powder, it was
      proposed in the present paper to build NIR models for a sample set composed of
      different types of milk powder. With 70 samples provided by one manufacturer, 6
      NIR models including acidity, fat, lactose, sucrose, protein and ash, were built
      by optimizing algorithms. The results indicated that these NIR models except the
      acidity model have good stability and high prediction ability (RSD<10%, RPD>3).

PMID- 18051518
TI  - [Research on discrimination method of orange juice variety based on spectroscopy
      technology].
AB  - In order to quickly analyze varieties of orange juice with near infrared spectra,
      firstly, principal component analysis (PCA) was used to analysze the clustering
      of orange juice samples, and the characteristic differentia of four orange juice
      varieties was obtained through qualitative analysis. Then plentiful spectral data
      were compressed by wavelet transform (WT) and the model was built with radial
      basis function neural network (RBF-NN), which offered a quantitative analysis of
      orange juice varieties discrimination. The model regarded the compressed data as
      the input of RBF-NN input vectors and built a RBF-NN model. Two hundred forty
      samples from four varieties were selected randomly to build the training model,
      which in turn was used to predict the varieties of 60 unknown samples. The
      discrimination rate of 100% was achieved by WT-RBFNN method. It was indicated
      that wavelet transform combined with RBF-NN is an available method for variety
      discrimination based on the near infrared reflectance spectroscopy technology. It
      offered a new approach to the fast discrimination of varieties of orange juice.

PMID- 18051519
TI  - [Application of near infrared sensor to the radio control count system].
AB  - Using reflective near infrared sensor, radio receiving/transmitting module and
      four-in-one function mix count integrated circuits, the radio control infrared
      counter was studied when a product enters the infrared surveillance area, part of
      the infrared signal will be reflected by the product, received by the
      photosensitive tube installed parallel with the transmitting tube, and
      transformed to a similar frequency electric signal, which is amplified by the
      internal circuits of infrared sensor module. After comparing and processing, a
      high level signal will be output to start transmitting module. When the receiving
      device receives the radio control encoded signal, it will demodulate and decode
      the signal, and send out an encoded pulse. By counting this pulse signal, the
      statistics of the products can be realized. The whole device is of a module
      configuration. It has the advantage of simple installing, strong anti-detonation
      ability, far distance-transmitting, work reliability, precise counting and high
      luminance digital display. It can be used in heavy industry, light and textile
      industry, food industry, and farming and animal husbandry, to radio control the
      count of yield or volume in some facilities or assembly lines.

PMID- 18051520
TI  - [Rapid measurement of citric acids in orange juice using visible and near
      infrared reflectance spectroscopy].
AB  - Visible and near infrared reflectance spectroscopy (Vis/NIRS) as a new method was
      proposed for the rapid and nondestructive measurement of citric acids in orange
      juice. High performance liquid chromatography (HPLC) was used as a reference
      method for the spectral analysis of citric acids. The original spectral data were
      preprocessed by the smoothing method with five smoothing points in order to
      eliminate the noise. Before modeling, large spectral data were compressed by
      wavelet transform (WT) in Matlab7.01 with the edited program to reduce the
      dimensions and modeling time, and then the new variables after being compressed
      were used to build PLS calibration in spectral software Unscrambler 9.5.
      Considering the effect of different wavelet functions and decomposed scales on
      the data compressed, the optimal wavelet function Db4 and decomposed scale 5 were
      determined by predictive residual error sum of squares (PRESS). A total of forty
      samples were used in our experiment, including thirty samples for the calibration
      model and ten unknown samples for the prediction. The quality of the calibration
      model was evaluated by the correlation coefficients (r) and standard error of
      calibration (SEC), and the prediction results were assessed by correlation
      coefficients (r) and standard error of prediction (SEP). Comparing WT-PLS model
      with PLS model, the result of WT-PLS model was r of 0.901 and SEP of 0.937, while
      the result of PLS model was r of 0.849 and SEP of 1.662, indicating that the
      prediction result from PLS model with wavelet transform was better than that from
      PLS model.

PMID- 18051521
TI  - [Influence of sample loading and test conditions on NIR veracity and study of
      analysis error source].
AB  - The influence of sample test conditions on the NIR veracity was studied with
      homemade grating diffuse NIR instrument using Yunnan flue-cured tobacco. Deducing
      analysis error was achieved by model self-emendation when a global NIR model was
      set up. Without regarding the influence of loading samples and test conditions,
      the test repetition error, re-loading error and samples tightness error, which
      were brought by instrument S/N, accounted for 50%, 30% and 20% of the total
      error, respectively. Depressing sample could reduce errors brought by sample
      tightness. Changes in test conditions could bring more analysis error, which was
      larger than the total of repetition error. These results theoretically explain
      the influence of sample test conditions on the NIR analysis veracity, which can
      provide basic theory data for farther improvement of homemade instrument and
      offer a new idea for resolving this problem.

PMID- 18051522
TI  - [Influence of sample annum and distribution of chemical values on NIR veracity].
AB  - The influence of sample annum and the distribution of sample component on NIR
      veracity was studied with homemade grating diffuse NIR instrument using Yunnan
      flue-cured tobacco. Results showed that sample annum had an obvious influence on
      the total sugar and nicotine models, but had an unconspicuous influence on the
      total-nitrogen model. Models set up by samples, whose component content
      distribution was normal school, was better than those set up by even
      distribution. The conclusion in this study has a significant referenced value for
      the method and principle to select representative samples to modeling from a
      large amount of specimens.

PMID- 18051523
TI  - [Surface enhanced Raman spectroscopic study on the gold-labeled protein self
      assembled surface].
AB  - The human IgG molecules were labeled with 13 nm gold nanoparticles and the
      complex of the gold-labeled human IgG molecules was immobilized on a silicon
      surface modified by 3-aminopropyltriethoxysilane and glutaraldehyde. The method
      increases not only the tightness but also the surface coverage for immobilization
      of the complex and retains protein configuration well on the silicon surface. The
      self-assembled complex surface was observed by AFM. The complex aggregated on the
      silicon surface and the "island" monolayer of the complex was obtained. Meanwhile
      the SERS spectrum of the complex self-assembled "island" monolayer on silicon
      surface was presented. In the present paper, the gold labeled human IgG molecules
      were self-assembled on the silicon surface, SERS spectra of protein were obtained
      and as SERS active substrates were provided for the study of the protein
      molecules.

PMID- 18051524
TI  - [Study of Raman spectra of single carcinoma of nasopharynx cell].
AB  - The Raman spectra from carcinoma of nasopharynx cell lines (CNE2) and normal
      airway epithelial cell lines (HBE) were investigated using a laser tweezers Raman
      spectroscopy (LTRS). The Raman scattering measurements were obtained from three
      different places in every single cell. Visual inspection of the spectra shows
      that the differences observed in spectra of the cancer cells and normal cells are
      obvious. The peak ratio I1 304/I1 336 is 1.05 for the normal cell and 1.22 for
      the cancer cell. Using a combination of principal component analysis (PCA) and
      discriminant function analysis (DFA), the authors are able to predict cancer
      cells, and normal cells and the DFA is better for single Raman spectrum. The
      sampling locations did not seriously affect the result of PCA and DFA. PCA and
      DFA also show that the uniformity of normal cells is better than that of cancer
      cells. The results indicate that the Raman spectra may offer the experimental
      basis for colorectal cancer diagnosis.

PMID- 18051525
TI  - [Excitation-emission-matrix spectral property of dissolved organic matter in
      seawater of Jiaozhou Bay, China].
AB  - Excitation-emission matrix spectroscopy (EEMs) was applied to measure the
      fluorescence properties of dissolved organic matter (DOM) in seawater collected
      from Jiaozhou Bay in June, 2005. The study areas include central Bay area,
      receptor areas of Dagu River, Licun River and Haibo River. The aim was to
      investigate the influence of discharges from several typical rivers to the
      receiving seawater. Dagu River discharges mostly freshwater, while the other two
      rivers discharges include more wastewaters from factories and sewages treatments.
      The results indicate that there is a redshift of the position of humic-like
      fluorescence peaks due to the discharges from sewages and wastewaters from
      factories. The intensities of protein-like and humic-like peaks were the
      strongest in the samples from area near Haibo River and Licun River, while the
      weakest fluorescence intensities of both protein-like and humic-like were
      observed in the samples collected from central bay area. This suggests that river
      inputs are the mains sources of DOM in seawater of Jiaozhou Bay, while DOM
      produced by bioactivity in situ dominates those in central Bay area. The
      relationships of protein-like and humic-like fluorescence intensities vary
      depending on the water samples. The DOM in seawater of Jiaozhou Bay may be
      polluted by protein-like organic matter produced by human activity, as indicated
      by higher ratios of protein-like and humic-like fluorescence intensities. The
      results suggest the potential utility of EEMs technique for trace DOM and land
      based pollution sources.

PMID- 18051526
TI  - [Progress in predicting animal feed intake of plant secondary compounds by
      spectral analysis].
AB  - Study on feed intake of phytophagic animals is a key issue in promoting animal
      productivity and conservation of wild life. However, how to accurately predict
      the feed intake of grazing animal and wild life is a long remaining problem.
      Under the mechanism of co-evolution, plant produces secondary compounds such as
      phenolics, terpenoids and nitrogen-containing compounds to avoid or reduce animal
      herbivorous damage as a defensive strategy, while animal attained detoxification
      capacity of biotransforming and mineralizing the compounds by microbial
      activities and reactions such as hydrolysis and reduction. The attributes of
      feedstuff and the amount of a particular feed consumed by the animal affect
      directly the urinary excretion of secondary metabolites. Plant secondary
      compounds and their metabolites can be efficiently extracted, separated and
      structure-identified by spectroscopic analytic method. Then the feed intake of
      the animal can be accurately measured or predicted by the inference model of
      concentration-ratio that is based on the regression of correlating the secondary
      metabolites to the precursors in plant. Aromatic compounds, an universal
      occurrence in vascular plants, play an important role in predicting feed intake
      of ruminants. Progresses have been made all-around about the new method.
      Intensive studies have found that different species and developing stage of plant
      have varying kinds and levels of secondary compounds, and the age, gender and
      type of animal have different capacity of metabolizing the compounds. Increasing
      concentrations of the compounds in the diet led to a dose-dependent decrease in
      food intake best described as an exponential decay. Animals that had not
      previously been exposed to the compounds ate significantly more when first
      offered food containing the compound than on subsequent days. Advanced
      spectroscopic analytic method has been developed and widely applied in extraction
      (e. g. microwave assisted extraction and ultrasonic extraction), separation and
      purification (e. g. paper chromatography, VLC, GC, HSCCC, Micro-LC and HPLC), and
      structure-identification (e. g. Fourier transform infrared spectroscopy,
      ultraviolet spectroscopy, and nuclear magnetic resonance spectroscopy) of plant
      secondary compounds and their metabolites. Studies suggest that some aromatic
      compounds like phenolic alkaloids, flavonoids, tannins, lignin and N-alkane are
      suited internal markers and find that the method to predict animal feed intake of
      plant secondary compound by spectral analysis is quick, accurate and applicable.
      The further focus should be on selecting appropriate compounds and their fate in
      metabolizing and excretion, and the development of intelligentized spectroscopy
      equipments.

PMID- 18051527
TI  - [Spectrofluorometric detection of protein with a novel hydrophilic cyanine dye].
AB  - A sensitive fluorescence quantitative determination for bovine serum albumin
      (BSA) or human serum albumin (HSA) has been developed by using a new hydrophilic
      cyanine dye 1, 1'-sulfonopropyl-3,3,3', 3'-tetramethylindolium-5,5'-disulfonic
      potassium (STDP) as a fluorescence probe. Using BSA as a representative protein,
      characteristics of the fluorescence reaction of STDP with protein were
      investigated. Effects of the concentration of the hydrophilic cyanine dye, pH
      value of the buffer solution, and ion-intensity of NaCl were also studied as well
      as the ratio of ethanol. In the citrate-HCl buffer solution, the fluorescence
      emission wavelength of BSA-STDP system was 562 nm with the maximum excitation
      wavelength of 548 nm, and the Stokes displacement was 14 nm. With the pH ranging
      from 1.0 to 2.0, the fluorescence was increasing and up to the maximum at pH 2.0.
      However, in the pH range of 3.0-5.0, the interaction of BSA and STDP was weakened
      due to the decrease in positive charge on the BSA chain, which resulted in an
      observable decrease of the enhancement of the fluorescence intensity. At the
      optimum pH of 2.0, electrostatic interactions of positive charges of the BSA
      chain and negative charges on the sulfonic groups of STDP were carried out. The
      interactions of the indole group of STDP and some active groups of BSA (viz.
      amido, carboxyl or sulfhydryl) were also achieved, and resulted in the
      combination of indole group of cyanine dye into the chain of BSA. So the
      hydrophobic effect and the protection provided by the skeleton chain of BSA were
      both improved to prevent the fluorescent energy of STDP from losing in the
      solution, which caused a notable fluorescence increase with an observable shift
      to the longer emission wavelength. Furthermore, with the augmentation of BSA, the
      alpha-helix structure of BSA molecular turned from the unwrapped state to the
      enfolded state, in favor of restraining free-oscillation of fluorescence probe in
      the solution and maintaining a high energy transfer efficiency. Such a fact
      fueled a highly enhancement of the fluorescence too. Besides, effects of the
      concentration of cyanine dye on the determination of BSA were also investigated.
      The fluorescence intensity (DeltaF) was enhanced with the increase in the
      quantity of STDP and gained the peak at 1.00 micromol x L(-1). However, when STDP
      ranged from 1.50 to 5.00 micromol x L(-1), some negative congregate effects on
      the nature of cyanine dye might happen and resulted in a too high fluorescence
      background. A rapid decrease of the fluorescence intensity was observed. The
      effects of ion-intensity of NaCl and ethanol on the fluorescence of BSA-STDP
      system were obvious. Though the fluorescence still remained high at the level of
      NaCl of 0.025 mol x L(-1), a rapid decrease happen at the level of NaCl from 0.05
      to 0.15 mol x L(-1). With the addition of ethanol, the dissolvation capacity of
      both STDP and BSA was improved and their interactions were accelerated. An
      increasing fluorescence with the augment of ethanol was obtained and the maximum
      was achieved with the ratio of ethanol at 10%. Influences of coexistent
      substances such as amino acid, metal ions such as Cu2+, Na+, Ca2+, Mg2+, Al3+ and
      Fe3+ were also investigated. Most substances had no notable influences on the
      determination of BSA except Fe3+ and Cu2+ ions. Under the optimum conditions, the
      fluorescence of STDP was enhanced markedly with the addition of the BSA or HSA
      protein. Good calibration curves of the proteins were obtained in the range of
      0.20-15.00 microg x mL(-1) for BSA and 0.20-12.00 microg x mL(-1) for HSA with
      detection limits (3sigma/K) of 0.01 microg x mL(-1). Applied to simulant BSA
      samples, this method was adaptable. And the results were satisfied with good
      recoveries ranging from 94.5% to 103.3% at the revels of 4.00, 6.00 and 8.00
      microg x mL(-1) respectively.

PMID- 18051528
TI  - [The study of fermentation liquid's absorption spectra in elastase fermentation].
AB  - The present article studied the fermentation liquid's absorption spectra,
      bacteria growth period and elastase' production in elastase fermentation, and
      compared and analyzed the their relation. The results show that the changes in
      the absorption spectra were closely related with bacteria growth and elastase'
      production. The UV spectroscopic technique is helpful for detecting the change of
      the organic nitrogen base and enzyme. The study offers a new method to detect
      fermentation process and is basic for detecting fermentation process on line by
      UV spectroscopic technique.

PMID- 18051529
TI  - [Studies on the interaction between puerarin and bovine serum albumin].
AB  - The interaction of puerarin and bovine serum albumin (BSA) under physiological
      condition was studied by fluorospectrophotometry. The experiment demonstrated
      that the quenching mechanism of puerarin a BSA was static quenching process. The
      quenching constant is 7.29 x 10(12) L x mol(-1) x s(-1), and the binding constant
      is 5.04 x 10(4) L x mol(-1). According to the Forster nonradiative energy
      transfer theory, the binding distance between donor (BSA) and acceptor (puerarin)
      was calculated to be 3.35 nm. The influence of the presence of puerarin on
      structure of BSA was studied by synochronous fluorescence method, the binding
      distance between BSA and puerarin was also measured, and the binding mechanism
      was discussed. In addition, the effect of some ions on the binding constant of
      puerarin with BSA was also studied.

PMID- 18051530
TI  - [Monitoring of photodynamic therapy of port wine stain by fluorescence
      spectroscopy].
AB  - The blood drug level and the formation of photoproduct were monitored during
      photodynamic therapy (PDT) of port wine stain (PWS) by fluorescence spectroscopy.
      The irradiation was implemented by a 532 nm double-frequency Nd:YAG laser, and
      the collection of fluorescence spectra was completed with the use of spectrograph
      and ICCD. In the experiment for validation of the system, the fluorescence basis
      spectra of hematoporphyrin monomethyl ether (HMME)-sensitized mouse normal skin
      were constructed, and, by least-square fitting, HMME fluorescence (624 nm) could
      be discriminated from that of photoproduct (652 nm). The fitting of fluorescence
      spectra measured from PWS patients skin containing PSD-007 was performed with the
      same basis spectra as those from the mouse skin. The curves of blood drug level
      of different patients with significant variance, as well as those of formation
      and bleaching of photoproduct were obtained. Fluorescence spectroscopy monitoring
      system and fitting method presented here can provide technical means for rigorous
      quantitative PDT dosimetry method, and the results obtained here will make for
      the individual scheme of PDT.

PMID- 18051531
TI  - [Preparation and spectra characterization of optically variable pigments with
      four symmetrical configurations].
AB  - The optically variable pigments with four symmetrical configurations were
      obtained by using the mica titanium as the host materials, which was pretreated
      in acid and alkaline condition. The reflection differences between the host
      materials and the coatings were increased by optimizing the number of layers and
      the arrangement order. The optically variable effect was investigated by X-Rite
      MA86II five angles spectrophotometer. The impact of symmetrical configurations on
      improving the color travel effect was studied, and the influence of different
      coating materials on the hue and the color travel effect was researched. The
      results show that the reflection rate and the color travel effect of the pigment
      were improved by coating another material on three symmetrical configurations.

PMID- 18051532
TI  - [Study on the spectrum response of Brassica Campestris L leaf to the zinc
      pollution].
AB  - In the present paper, the spectrum response of Brassica Campestris L leaf to the
      stress of heavy metal zinc pollution was studied in three spectral rangess of the
      red edge position (680-740 nm), the visible spectrum (460-680 nm) and the near
      infrared spectrum (750-1000 nm). The results indicate that the Zn content in
      cabbage leaves increases and the chlorophyll level reduces with the increase in
      Zn concentration in soil. With the Zn content of Brassica Campestris L leaves
      increasing, the leaf spectral reflectivity in visible light (A1) and the range of
      red edge shift (S) ascends, the the leaf spectral reflectivity in the near
      infrared light (A2) decreases. The three indices of A1, A2 and S are fitted much
      linearly with the logarithm of zinc content in Brassica Campestris L leaves with
      the high squared regression coefficients of 0.942, 0.981 and 0.969 respectively.
      The regression models are reliable to estimate the zinc content in Brassica
      Campestris L leaves.

PMID- 18051533
TI  - [Fluorescence microscopic study of environmental water sample by a self-ordered
      ring technique with microwave heating].
AB  - A self-ordered ring (SOR) technique with microwave heating is proposed for the
      environmental water samples based on the capillary flow of solvent on the solid
      surface of glass slide support. In the reaction medium of pH 4.58 HAc-NaAc
      containing poly (vinyl alcohol)-124, a SOR of berberine with the outer diameter
      of 1.1 mm and the ring belt width of 19.2 microm can be formed using microwave
      heating and its fluorescence was quenched by picric acid. The maximum
      fluorescence intensity (Imax) was found to be proportional to picric acid
      content. When a 0.1 microL droplet of berberine-picric acid mixture was spotted
      on the solid surface, picric acid in the range of 1.3-30.0 x 10(-7) mol x L(-1)
      can be detected, and the limit of detection can reach 1.3 x 10(-8) mol x L(-1).
      With the present method, the contents of picric acid in natural water samples and
      synthetic samples were satisfactorily determined with its recoveries of 96.3%
      108.0% and RSD lower than 3.3%. The sensitivity enhanced 50 times than that by
      spot analysis, and 60 times than that in solution. Moreover, the interference
      from background was reduced greatly. The authors believe that the SOR technique
      will find wide practicability and superiority in both environment and
      biochemistry.

PMID- 18051534
TI  - [Applications of quantum dots to biological probes].
AB  - Quantum dots (QDs) have shown unique optical properties compared with traditional
      organic dyes. Now, more and more attention has been paid to them, especially in
      the fields of biological medicine and materials. Much work about QDs application
      in biology has been done by many researchers. In resent years, QDs have been
      widely used as biological probes. By observing the conjugation site between QDs
      and target molecules or tracking the movement of QDs in live cells, some
      information about transferring signals mechanism may be obtained, therefore,
      offering apparent evidence for controlling cell's growth and finding the factors
      in the deterioration of cancer. In the present paper, interactions among macro
      molecules are introduced with fluorescence resonance energy transfer (FRET),
      fluorescent labeling of biological macro molecules, labeling and imaging of cells
      and tissues, and imaging in vivo. Furthermore, some developments and problems in
      application are summarized. Thirty seven references are cited.

PMID- 18051535
TI  - [Application of hyperspectral data to the classification and identification of
      severity of wheat stripe rust].
AB  - Wheat stripe rust, caused by Puccinia strii formis f. sp. tritici, is one of
      pandemic diseases causing severe losses in China. Monitoring and warning of this
      disease is principal for its precise prediction and for implementing effective
      measures to control it. The hyperspectral data used for analysis were attained
      from 88 leaves including healthy leaves and infected leaves over a range of
      disease severity levels. Support vector machine (SVM) was applied to classify and
      identify the severity of wheat leaves infected by the pathogen. The model was
      built based on 44 proof-read samples to estimate 44 proof-test samples. And the
      identification accuracy is totally 97%. So SVM can be used in the classification
      and identification of severity of wheat stripe rust based on attained
      hyperspectral data.

PMID- 18051536
TI  - [The common and variation peak ratio dual index sequence analysis on UV
      fingerprint spectra of Paeonia Lactiflora Pall].
AB  - Baishao and Chishao (Paeonia Lactiflora Pall.) and their close relative Danpi
      (Paeonia Suffruticosa Andr) samples were estimated quantitatively, based on their
      UV fingerprint spectra of the extracts obtained with chloroform, ethanol and
      water, by applying the common and variation peak ratio dual index sequence
      analysis method. The analytical results showed that the Baishao samples B2, B3
      and B4 from the closest regions were the most similar samples. Their common peak
      ratios were larger than 70 percent and their variation peak ratios were less than
      33.3 percent. However, there existed obvious differences among Baishao sample
      group 1 (B1 and B5), group 2 (B2, B3 and B4) and group 3 (B6) from different
      regions. The common peak ratios among group 1 (B1 and B5) and group 2(B2, B3 and
      B4) were lower than 60 percent, while those among group 1 (B1 and B5) and group 3
      (B6) were less than 57 percent. The Baishao samples B1 and B5 from the same
      region collected in different years were of significant disparity, their common
      peak ratio was only 44.4 percent, but their variation peak ratios were larger
      than 100 percent. In fact, this method reaches the limitation of quantitative
      identification of herbs, and can distinguish at least two samples quantitatively.

PMID- 18051537
TI  - [Spectroscopic study the interaction of cucurbit[n]urils with 1-naphthol, 2
      naphthol].
AB  - Interaction of cucurbit[n]urils with two naphthol isomers and the influence of pH
      on the interaction were studied by using UV-Vis spectroscopy and fluorescence
      spectrophotometry. The experimental results revealed that cucurbit[8]urils always
      forms a 1:1 complex with the naphthol isomers. However, UV-Vis spectroscopy and
      fluorescence spectrophotometry method showed no obvious interaction of
      cucurbit[6]urils and cucurbit[7]urils with naphthol isomers in all pH values.
      Formation constant of Kf was found to be 4.2 x 10(4) L x mol(-1), 1.6 x 10(4) L x
      mol(-1) of 1-naphthol and 2-naphthol with cucurbit[8]urils respectively by using
      fluorescence spectrophotometry. Formation constant of Kf was found to be 4.2 x
      10(4) L x mol(-1), 5.4 x 10(4) L x mol(-1) of 1-naphthol and 2-naphthol with
      cucurbit[8]urils respectively by using UV-Vis spectroscopy. There is no
      interaction between cucurbit[8]urils and the naphthol isomers in strong
      alkalescent medium. The cucurbit[8]urils could include the guest with a 1:1 ratio
      in acid and neutral medium.

PMID- 18051538
TI  - [Study on influence of pH on interaction of cucurbit[n=7,8] uril with two
      naphthylamine isomers].
AB  - The interaction of cucurbit[n=7,8]urils (Q[7], Q[8]) with two naphthylamine
      isomers and the influence of pH on the interaction were studied by using UV-Vis
      spectroscopy and 1H NMR technique. The experimental results revealed that Q[7]
      always forms a 1:1 complex with the naphthylamine isomers respectively in the pH
      range (-0.3<pH<8) and the interaction of Q[7] with the title guests was not
      observed in the 8<pH<14 range. However, there are five interaction stages for
      Q[8]-naphthylamine isomer systems, no obvious interaction between the host Q[8]
      and the title naphthylamine guest(s) at the "highest" and the "lowest" pH (pH>14
      and pH<-0.3 respectively); the Q[8] could include the guest with a 1:1 ratio
      between the "highest" and a "higher" pH or the "lowest" and a "lower" pH (
      0.3<pH<4 and 9.5<pH<14); between the higher and the lower pH (4<pH<9.5), the Q[8]
      includes the guest and forms a inclusion complex with 1:2 ratio of host to guest.

PMID- 18051539
TI  - [Spectroscopic studies on the binding of phenazopyridine hydrochloride and bovine
      serum albumin].
AB  - The binding of phenazopyridine hydrochloride and bovine serum albumin under
      physiological conditions was studied by spectroscopic method. The quenching
      mechanism of the fluorescence of bovine serum albumin by phenazopyridine
      hydrochloride was studied with fluorescence and absorption spectroscopy. The
      binding constant Kb and the number of binding sites n were determined at
      different temperatures according to Scatchard equation, and the main binding
      force was discussed by thermodynamic equations. The effect of the drug on bovine
      serum albumin conformation was also studied by using synchronous fluorescence
      spectroscopy. The quenching mechanism of phenazopyridine hydrochloride to bovine
      serum albumin is static quenching and non-radiation energy transfer. The binding
      constants Kb at 15, 25 and 37 degrees C are 2.47 x 10(7), 9.15 x 10(6) and 4.36 x
      10(6) mol(-1) with one binding site, respectively. The thermodynamic parameters
      of the reaction are DeltaH = -71.2 kJ x mol(-1), and DeltaS = 124.8 J x mol(-1) x
      K(-1). Binding phenazopyridine hydrochloride to bovine serum albumin is a
      spontaneous inter-molecular interaction in which entropy increases and Gibbs free
      energy decreases. The binding distance r between phenazopyridine hydrochloride
      and bovine serum albumin is 1.61 nm according to Forster theory of non-radiation
      energy transfer. The binding force is electrostatic interaction. Phenazopyridine
      hydrochloride can be deposited and transported by serum protein in vivo.
      Phenazopyridine hydrochloride does affect the serum protein conformation.

PMID- 18051540
TI  - [Pollution characteristics analysis of Hg, Pb and As in soils of nonferrous metal
      mine area by the BCR and HG-ICP-AES technique].
AB  - A method for the determination of Hg, Pb and As concentrations in soil and
      sediment samples by the BCR and HG-ICP-AES technique was described. Under the
      optimum experimental conditions and instrumental operation parameters, the
      detection limits of Hg, Pb and As of the method were 0.6, 1.5 and 0.8 ng x mL(-1)
      , respectively. Meanwhile, the analytical results of Hg, Pb and As in the Chinese
      national standard sediment reference samples were in good agreement with the
      certified values with the RSDs below 8%. Using the BCR and HG-ICP-AES technique,
      the content of each chemical species of Hg, Pb and As in soils of nonferrous
      metal mine area in western Hunan province was studied. The result showed that the
      Hg, Pb and As contents in soils were dominated by residual form, followed by
      organic and Fe-Mn oxides form, whereas acid-exchangeable form was rather low. The
      concentrations of the four Hg species in mine soil were 1.2, 3.0, 47 and 272
      times higher than those in the control soil. While the concentrations of Pb and
      As in the same samples were 1.2, 4.6, 8.1 and 4.5 times and 1.5, 2.9, 3.3 and 2.2
      times higher than those in the control soil, respectively. The results indicated
      that the soil in mine area in western Hunan province was co-polluted polluted by
      Hg, Pb and As.

PMID- 18051541
TI  - [Determination of copper, chromium and arsenic in wood and its products by high
      pressure digest-ICP-AES].
AB  - Sample preparation was studied, samples were sawn to be sawdust, screened by a 35
      mesh sieve, dryed 4-5 h at 105 degrees C, and its homogeneity was tested by
      variance analysis. Sample pretreatment methods were investigated with wet
      decomposition, dry ashing, high pressure digest (including microwave-assisted
      closed digestion and steel liner PTFE vessel digestion). According to the
      comparative results, wet decomposition is fit for testing soluble copper,
      chromium and arsenic. Dry ashing and high pressure digest are fit for testing
      total copper, chromium and arsenic, but arsenic is easy to lose in dry ashing.
      Acidity effect and matrix effect were discussed. A method was proposed for the
      determination of total copper, chromium and arsenic in wood and its products by
      high pressure digest-ICP-AES. The detection limit of copper, chromium and arsenic
      was 1.2, 0.2 and 7.1 mg x kg(-1), respectively, RSDs were in the range of 0.2%
      1.5%, and recoveries were between 92% and 106%. Using this method, more
      reasonable results will be given for controlling toxic substances from wood and
      its products and their wastes. This method has been applied to practical sample
      analysis.

PMID- 18051542
TI  - [Study on the method of using ICP-MS to determine microelements in the animal
      feed].
AB  - The method for the determination of microelements such as Cu, Zn, Fe, Mn, Cr, Cd,
      Pb, As and Se in the animal feed by inductively coupled plasma-mass spectrometry
      was developed. The operation parameters, spectrum interference, matrix effect and
      memorial effect were studied in detail. Under optimal condition, the detection
      limits of these nine elements were from 2.03 x 10(-3) to 3.17 microg x L(-1), and
      the linear range was over three orders with a correlation coefficient above
      0.999. This method was applied directly to determine microelements in real
      samples involving the standard wheat powder, formular feed and pre-mix feed. The
      determination results of microelements in the standard wheat powder accorded with
      reference results. The recovery of microelements in the formular feed was from
      86% to 115%, and the relative standard deviations < or = 8.2% (n = 6). The
      results of elements content in the pre-mix feed were identical with those
      determined by national standard method. This method is simple, sensitive,
      accurate and can perform simultaneous multi-elements determination compared with
      conventional method of animal feed determination. The results were satisfactory.

PMID- 18051543
TI  - [Change of the trace elements content from cigarettes (tobacco) to its ash and to
      look at harm of stuck cigarette].
AB  - After the digestion of cigarettes and its ash are digested with concentrated
      nitric acid and perchloric acid, the change in mineral elements (Ca, Mg, Cu, Fe,
      Zn, Mn, Ni, Co, Cr, Pb and Cd) content in the cigarette and its ash were
      determined by flame atomic absorptionspectrophotometry. The experimental results
      showed that there were differences between the cigarette (tobacco) and its ash,
      especially, the contents of Pb and Cd harmful to human health in the ash are
      lowed 26.4% and 44.2%, respectively. It is concluded that a part of Pb and Cd in
      the cigarette passes through the human lung respiration and air environment.

PMID- 18051544
TI  - [Determination of microelements in different parts of Limonium bicolor by FAAS].
AB  - Eight microelements in the flower, stem, leaf and root of limonium bicolor were
      determined by FAAS. Different parts of the powder were digested with HNO3-HClO4
      mixed acid (4+1) before the determination. Work conditions, accuracy and
      precision of the method were studied. The experimental results show that the
      recovery (n = 7) is 99.3%-105.3%, while RSD (n = 7) is 0.34%-1.04%. The content
      of each microelement in the different parts of limonium bicolor is not the same.
      For the flower: Na>K>Mg>Ca>Fe>Zn>Co>Cu, stem: K>Mg>Ca>Na>Fe>Zn>Cu>Co, leaf:
      K>Mg>Ca>Na>Fe>Zn>Co>Cu, and root: K>Mg>Na>Fe>Ca>Zn>Cu>Co, but the contents of K,
      Mg, Cu, Na and Fe in all different parts of limonium bicolor are relatively high.
      The method has good precision and accuracy so that it is able to meet the
      requirements for analysis.

PMID- 18051545
TI  - [Determination of selenium in Tricholoma giganteum by flow injection-hydride
      generation-atomic absorption spectrometry].
AB  - Various test conditions and effect factors for the determination of selenium by
      flow injection-hydride generation-atomic absorption spectrometry were discussed
      and a method for the determination of selenium in tricholoma giganteum has been
      developed. The linear range for selenium is 0-50 microg x L(-1). The relative
      standard deviation is less than 3% and the recovery is 96%-105%. This method is
      simple, rapid and has been applied to the determination of selenium in tricholoma
      giganteum with satisfactory results.

PMID- 18051546
TI  - [Determination of trace elements in cardiocrinum giganteum by FAAS].
AB  - Conditions for simultaneous determination of multi-tract elements in Cardiocrinum
      giganteum by flame atomic absorption spectrometry were studied. Elements K, Ca,
      Na, Mg, Fe, Zn, Mn, Cu and Cr in different growth periods of Cardiocrinum
      giganteum were determined, the relative standard deviation of the method is
      between 0.20% and 2.1%, and the recovery is between 97.8% and 104.9%. Analytical
      results were satisfactory. The results showed that some elements essential to
      human such as Zn, K, Ca, Mg and Mn in Cardiocrinum giganteum are abundant,
      implying that the nutritive value of Cardiocrinum giganteum is high.

PMID- 18051547
TI  - [Study of the sensitizing effects of surfactants on the determination of aluminum
      by air-acetylene flame atomic absorption spectrometry].
AB  - The sensitizing effects of ten surfactants, such as cetyl trimethyl ammonium
      bromide (CTMAB) and cetyl pyridinium chloride (CPC), on the determination of
      aluminum were studied. The results showed that the cationic surfactants in the
      experiment were good sensitizers for the determination of aluminum, and the
      sensitization time was about 3.0. On the other hand, anionic surfactants had
      inhibition action, while particular surfactants had no action. With the
      sensitizing agent of CTMAB, the operating parameters of the spectrometer and the
      effects of CTMAB, solution medium and interfering elements in aluminum-nickel
      alloy sample were studied. The content of aluminum in aluminum-nickel alloy
      sample was determined by air-acetylene flame atomic absorption spectrometry, the
      linear range of aluminum of this method was 0.10-2.0 g x L(-1), the relative
      standard deviation was 2.6%, and the recoveries were in the range of 97%-103%.

PMID- 18051548
TI  - [Indirect determination of Vc with flame atomic absorption spectrometry].
AB  - In the present paper, a new method for indirect determination of Vc by atomic
      absorption spectrometry is proposed, based on the reducing properties of Ag+. The
      effects of temperature, reaction time and use level of Ag+ on the experiment were
      studied. Room-temperature and reaction time of 35 minutes were chosen. The
      oxidant amount is 2.0 mL solution of Ag+ (1.0 microg mL(-1)). Meanwhile the AAS
      working conditions for Ag determination were optimized. The proposed method
      allows the determination of Vc in a wide range with a relative standard deviation
      of 2.04%, and the detection limit is less than 1 microg x mL(-1). The method
      cannot be disturbed by the colour of sample. The interference of coexistent
      substance is also weak. Other methods for determining Vc could be remedied by
      this method. Two kinds of standard curves were plotted, standard working curve of
      sliver and standard working curve of Vc. The former is easier, while the latter
      is more accurate and could be applied flexibly according to the physical
      circumstances. This method is easy to control and has been applied to the
      determination of ascorbic acid in pharmaceutical preparations and orange juice.
      The recovery ratio of this method is 99.30%-106.06%. The results obtained in the
      analysis agreed well with the iodimetry in pharmacopeia.

PMID- 18051549
TI  - [Novel identification of donkeyhide glue by X-ray fluorescence analysis].
AB  - A new fast identification method for a Chinese patent medicine donkeyhide glue
      was established. Six samples from different producing areas were collected and
      determined by X-ray fluorescence analysis(XRF). Elements characteristic graphs
      were plotted and compared with those from the comparison sample. Many elements
      such as Ca, Na, Cl, K, Fe, Zn, Al, Mg, etc are contained in the six samples, but
      the contents of elements Cl, Ca, Na and K are obviously different. Some other
      microelements occur only in one or two samples. According to the above
      differentia the counterfeits of donkeyhide glue can be distinguished successfully
      by XRF. XRF is accurate, robust a nd objective, and could b e applied in t he
      discrimination of o th er traditionalChinese medicines.

PMID- 18051550
TI  - [Study on absorption spectra of cell substrate for Hep-2 cell after being
      radiated by X-ray].
AB  - UV-absorption spectra of the Hep-2 cell's culture medium RPMI1640 (10% Foetal
      Calf Serum) were collected by UV-3101 spectrophotometer after the Hep-2 cell was
      radiated by X-ray and cultivated for 24, 48 and 72 h, and the absorbability of
      the proteins in the substrate was analyzed. From these results it was found that
      there were visible differences among these absorption spectra. In particular, the
      absorption peaks of the RPMI1640 culture medium during the cultivation shifted
      from 233 to 235 nm, while the absorption peak at 278 nm became more and more
      smooth and even finally disappeared with the cultivation time. On the other hand,
      the absorption intensity of the different-dose groups rose greatly with the time,
      and were all lower than the control group until the cells were cultivated for 72
      h after being radiated by X-ray. It was showed that the content of each amino
      acid has already changed. That is, during the growing course of the cancer cells,
      the tryptophan and casein were not depleted equivalently. And there were some
      important relations between the absorption spectra and the cells' apoptosis and
      necrosis induced by X-ray. This will be a foundation for the study of the best X
      ray dose for the larynx carcinoma.

PMID- 18051551
TI  - [Method for determination of RE2O3 by X-ray fluorescence spectrometry].
AB  - A simple and rapid quantitative method for determining RE2O3 in rare earth oxide
      by X-ray fluorescence spectrometry was developed. A new method for manufacturing
      sample was brought up. The sample pedestal plate was lathed with
      polytetrafluoroethylene. A filter paper located in the sample pedestal plate was
      used to absorb 1 mL analytical solution, dried under infrared lamp or in stove
      and measured by X-ray fluorescence spectrometry with a 6 microm covering film. No
      remainder was detected in the sample pedestal plate. Vanadium was confirmed as
      the internal standard to compensate the influence of the location of absorbing
      filter paper within the sample pedestal plate, the analytical range was large,
      the accuracy and precision were satisfactory, the results agreed with other
      methods, and the method has been used in routine analyses for ten years. Also the
      method for manufacturing sample has been applied to a variety of materials.

PMID- 18051552
TI  - [The study on energy band structure of silicon nanowires with XPS].
AB  - Silicon nanowires were obtained via oxide-assisted method, which was operated in
      a high temperature furnace at 1250 degrees C under 1000 Pa for 5 h using Ar as
      carrier gas. The silicon nanowires were etched with 5% HF aqueous solution for 5
      min, and reacted with 1 X 10(-3) mol X L(-1) AuCL3 solution, and Au-modified
      silicon nanowires were obtained. The crystal structure of the products was
      characterized with XRD, and both of the patterns of Si and Au were observed. The
      morphology checked with SEM and TEM indicated large scale uniform silicon
      nanowires and Au particles on the surface of silicon nanowires. The average
      diameter of Au nanoparticls was 8 nm. The energy band structures obtained with
      XPS showed that gold nanoparticles are in negative charge and exist both at donor
      and acceptor levels. The Fermi level moved towards the top of valence band due to
      oxygen.

PMID- 18051553
TI  - [Beam hardening simulated correction research for X-ray TICT in testing
      composites workpiece].
AB  - In X-ray TICT, when X-ray is transmitted in the materal, the phenomenon of energy
      spectrum hardening takes place, resulting in artifacts. Thus, hardening
      correction has to be done. In the present paper, the phenomenon of X-ray beam
      hardening resulting in analyized, and the relation between the X-ray beam sum and
      the transmission thickness in testing composites workpiece is discussed.
      According to the Beer law and the characteristics of the interaction between X
      ray and the material, and getting the data of X-ray beam sum, the relation
      equation between the beam sum and transmission thickness is simulated firstly,
      and testing composites workpiece. Then, the relation and the method of
      equivalence are carried out between the equivalent transmission thickness and the
      transmission thickness for X-ray beam sum being corrected for monochromatic ray
      beam. Finally, the attenuation coefficient beam hardening simulated value for X
      ray equivalent monochromatic is reasoned out in testing composites workpiece.
      Then, the attenuation coefficient simulated value that has been corrected is used
      for product back-projection reconstruction. Thus, the effect caused by X-ray beam
      hardening is wipped off effectively in testing composites workpiece.

PMID- 18051555
TI  - [Preparation and spectra analysis of nano-ZnS].
AB  - The nano-zinc sulfide was prepared in RPBR (rotating packed bed reactor) using
      zinc nitrate and hydrogen sulfide as the raw materials. The size and morphology,
      crystal structure, composition and optical properties of the nano-zinc sulfide
      were analyzed by transmission electron microscopy (TEM), X-ray diffraction (XRD),
      X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectrometry
      (FTIR), UV-visible spectrophotometer and energy dispersive X-ray detector (EDX).
      The results show that the nano-zinc sulfide particles are spherical and their
      average size is about 42 nm. The XRD pattern shows that the nano-zinc sulfide is
      in a good sphalerite crystal phase. The XPS spectra show that the binding energy
      of the S (2p) is 162.6 eV, while those of the Zn 2p3/2 and 2p1/2 are 1021.4 and
      1044.6 eV respectively. The IR spectrum shows that the nano-zinc sulfide has good
      transmittance within the wavelength number range from 400 to 4000 cm(-1). The UV
      Vis spectrum shows that the nano-zinc sulfide has strong absorption within the
      wavelength range from 200 to 340 nm. The optical gap of the nano-zinc sulfide is
      3.57 eV by calculation. The EDX spectrum shows that the nano-zinc sulfide has
      high purity.

PMID- 18051554
TI  - [Determination and analysis of toluene diisocyanate metabolites in mice using gas
      chromatography-mass spectrometry].
AB  - In the present research we used gas chromatography-mass spectrometry (G C-MS) to
      determine metabolites of toluene diisocyanate (TDI) in mice and deduce the
      pathway for toluene diisocyanate metabolism in the organism. Conditions for TDI
      chromatography: Supelco PTETM-5 chromatographic column (30 mm x 0.25 mm x 0.25
      microm); initial column temperature: 90 degrees C, which was maintained for 30
      min, then the temperature was increased at a rate of 40 degrees C x min(-1) to
      280 degrees C, and maintained for 5.25 min; temperature for the vaporizing
      chamber: 250 degrees C; carrier gas: helium flowing at 1.0 microL x min(-1).
      Conditions for chromatography of TDI metabolites in the organism: 94% methyl, 4%
      ethenyl-bonded-phase fused-silica capillary column (30 + 2 m x 0.25 + 0.02 mm);
      initial column temperature: 30 degrees C, which was maintained for 5 min, after
      and then was increased at a rate of 80 degrees C x min(-1) to 280 degrees C, and
      maintained for 5 min; temperature for the vaporizing chamber: 250 degrees C;
      carrier gas: helium flowing at 1.0 microL x min(-1). Conditions for mass
      spectrometry: EI for ionization; 70 eV for ionization energy; 280 degrees C for
      connecting tube temperature; 35-350 micro for range of scanning; and 1.0 microL
      for sample size. The results showed that 2 ,4-toluene diisocyanate was
      metabolized into 2,4-diaminotoluene. Under the conditions selected for GC-MS, TDI
      metabolites in the organism can be isolated and identified.

PMID- 18051556
TI  - [Structure and photoluminescence of ASnO3 (A = Ca, Sr and Ba) : Eu
      nanocrystalline].
AB  - The present paper reports the photoluminescence properties of nanocrytalline
      ASnO3 (A = Ca, Sr and Ba) : 1% Eu phosphor synthesized by the Pechini-type sol
      gel method. The powder was characterized by X-ray diffraction (XRD), UV-Vis
      absorption spectra, transmission electron microscopy (TEM) and photoluminescence
      measurements. The experimental results show that BaSnO3 has the ideal cubic
      peroskite structure, while SrSnO3 and CaSnO3 are both distorted from cubic
      symmetry by an octahedral tilting distortion. The difference of structure in
      induced the different spectral properties of ASnO3 : 1% Eu. On the other hand,
      when A2+ changes from Ca2+ to Ba2+, the luminescence intensity becomes weak. So
      CaSnO3 : 1% Eu seems to be a good candidate for new phosphors.

PMID- 18051557
TI  - [Supervised feature extraction based on FDA and galaxy spectra classification].
AB  - With the recent technological advances in wide field survey astronomy and the
      implementation of several large scale astronomical survey proposals, celestial
      spectra are becoming very rich and the study of automated processing methods is
      attracting more and more attention. In the present work, the authors pointed out
      that it is necessary to investigate supervised feature extraction by analyzing
      the characteristics of the spectra classification research in literature and the
      limitations of unsupervised feature extraction methods. And the authors studied
      supervised feature extraction based on Fisher discriminant analysis (FDA) and its
      application in galaxy spectra classification. FDA could effectively reduce
      dimension and extract the features based on the classifying capability by fusing
      information in training data. Experiments show its superior performance in
      dimensional reduction for galaxy spectra classification.

PMID- 18051558
TI  - [Attaching importance to the management of allergic rhinitis in children].

PMID- 18051559
TI  - [Genetic epidemiological study on allergic rhinitis in Nantong region of Jiangsu
      Province].
AB  - OBJECTIVE: To explore the effects of genetic factors on the occurrence of
      allergic rhinitis (AR). METHODS: The morbidity rate of AR was surveyed by
      multistage sampling among 95 300 individuals (23,825 families) in Natong region,
      Jiangsu province. And a genetic epidemiologic investigation on AR was carried out
      to estimate the segregation ratio and heritability (h2) of AR by the methods of
      Li-Mantel-Gart and Falconer respectively. RESULTS: The morbidity rate of AR in
      Natong region was 1.20% (Male 1.21%, Female 1.18%, no statistical significance
      between them); By the data of the AR ancestry, the segregation ratio of AR in
      Nantong region was 0.078, significantly less than 0.25, and the genetic model
      belonged to polygenetics. The 1st, the 2nd, and the 3rd generation h2 of AR were
      (82.6 +/- 2.19)%, (80.8 +/- 2.93)%, (78.4 +/- 7.04)%. The h2 of AR was (81.86 +/-
      1.70)%. In the ancestry of AR, the morbidity rate of the 1st generation with AR
      was 12.11%; the 2nd generation with AR was 5.12%; the 3rd generation with AR was
      2.75%; and the morbidity rate of AR in general population was 1.20%. CONCLUSIONS:
      The heredity in family with AR is obvious. Several genes plus the environmental
      factors may cause AR, which accords with the characteristics of the polygene
      heredity disease.

PMID- 18051560
TI  - [Cardiac safety evaluation of loratadine in the treatment of allergic rhinitis in
      elderly patients].
AB  - OBJECTIVE: To evaluate the cardiac safety of the second-generation H1
      antihistamine loratadine in the treatment of allergic rhinitis in elderly
      patients. METHODS: Forty patients with perennial allergic rhinitis were enrolled
      in the study. There were 25 males and 15 females, aged 50 to 88 years (mean, 64.4
      years-old). 17 cases (42.5%) had a history of cardiovascular diseases and/or
      presented abnormal ECG parameters, but had no prolonged QT-interval. The subjects
      received loratadine 10 mg once-daily for 30 days. A series of baseline ECG
      recordings was obtained before treatment. ECG effects of the treatments were then
      compared with the baseline ECGs. RESULTS: There were no changes in sinus rhythm
      in all patients 30 days after treatment by loratadine. No statistically
      significant difference was found between the heart rates, P durations, PR and QRS
      intervals at baseline and end-point ECGs (P > 0.05), with no significant
      prolongation of the QT as well as QTc corrected for heart rate using Bazett'
      formula (P > 0.05). CONCLUSION: The results suggest no cardiotoxicity of
      loratadine, at the usual recommended dose, in long-term treatment of allergic
      rhinitis in the elderly.

PMID- 18051562
TI  - [Differential gene expression profile in seasonal allergic rhinitis with and
      without asthma].
AB  - OBJECTIVE: To screen the differential expression gene profile in nasal mucosa of
      seasonal allergic rhinitis (SAR) and SAR with asthma, oligonucleotide microarray
      (Affymetrix HG-U133-plus2) was employed to analyze the changes of gene
      expressions with GeneSpring software. METHODS: Inferior turbinate mucosa was
      obtained from five SAR patients and four SAR with asthma patients. Total RNA was
      extracted from the nasal mucosal biopsies and pooled into one SAR control pool
      and one SAR with asthma patient pool, and biotin-labeled cRNA probes were
      hybridized with Affymetrix HG-U133-plus2 array. The hybridization results were
      confirmed by RT-PCR analysis. The analysis of differential expression profiles
      were performed by GeneSpring software 7.3. RESULTS: Out of 47,000 analysed
      transcripts, 1,900 genes were differentially expressed at least 2-fold in which
      849 genes were up-regulated and 1,051 genes were down-regulated in nasal mucosa
      of SAR with asthma patients compared with that in SAR patients. These genes were
      involved in cell metabolism, gene transcription, cell proliferation, signal
      transduction, immune response, enzyme activity, transmembrane receptor activity,
      cytoskeletal protein binding, and many other aspects. Pathway analysis displayed
      161 groups, of which including more than 20 genes were as follow: cytokine
      cytokine receptor interaction, focal adhesion, cell adhesion molecules (CAMs),
      regulation of actin cytoskeleton, cell communication, gap junction, MAPK
      signaling pathway, calcium signaling pathway, leukocyte transendothelial
      migration, and purine metabolism. CONCLUSIONS: The data suggested that
      multigentic expression and regulation changes were involved in the development of
      SAR and SAR complicated with asthma, whose molecular mechanisms might be
      elucidated by identification of these differential genes.

PMID- 18051561
TI  - [Relationship between alpha- and beta-isoform of corticosteroid receptors and
      corticosteroid resistant allergic rhinitis].
AB  - OBJECTIVE: To clarify the relationship between the expression of alpha- and beta
      isoform of corticosteroid receptors (CS) in peripheral blood mononuclear cell
      (PBMC) and response to corticosteroid in patients with allergic rhinitis (AR).
      METHODS: Semi-quantitative RT-PCR was used to detect the expression of CS-alpha,
      beta in PBMC in patients with AR and to observe the different responses to
      corticosteroid in controls. Immunocytochemical assay was used to detect the
      expression of protein of CS-alpha and CS-beta. RESULTS: 1) The expression of CS
      alpha mRNA was detected in the sensitive group and the resistant group of
      patients with AR and the controls with CS-alpha/GAPDH mRNA (x +/- s) 1.15 +/-
      0.75, 1.63 +/- 0.78, 1.27 +/- 0.51 respectively. 2) The expression of CS-beta
      mRNA in PBMC in the resistant group of patients with AR was significantly higher
      than that in the sensitive group and the controls (P < 0.05), with CS-beta/GAPDH
      mRNA 1.42 +/- 0.73, 0.82 +/- 0.59, 0.80 +/- 0.68 respectively. 3) The number of
      CS-beta-positive PBMC in the resistant group was significantly higher than that
      in the sensitive group and the controls (P < 0.01), with the number of CS-beta
      positive PBMC 28.8% +/- 9. 9%, 5.9% +/- 3.2%, 5.5% +/- 6.8% respectively.
      CONCLUSIONS: It is shown that the excessive expression of CS-beta may serve as a
      novel predictor of corticosteroid resistance in patients with AR.

PMID- 18051563
TI  - [Prenatal diagnosis for hereditary deaf families assisted by genetic testing].
AB  - OBJECTIVE: To provide prenatal diagnosis for deaf families, which the first child
      was confirmed to be hereditary deafness caused by gap junction beta-2 (GJB2) or
      SLC26A4 (PDS) mutation, to avoid another deaf birth in these families. METHODS:
      Eight deaf families joined in this study. Each family had one child with severe
      to profound hearing loss while parents had normal hearing except a deaf father
      from family 8; mothers had been pregnant for 6-28 weeks. Genetic testing of GJB2,
      SLC26A4 and mitochondrial DNA (mtDNA) A1555G mutation were firstly performed in
      probands and their parents whose DNA was extracted from peripheral blood, and
      then prenatal testing was carried out in the fetus whose DNA was extracted from
      different fetus materials depending on the time of gestation. RESULTS: The
      probands from family 1-4 were found to carry homozygous or compound GJB2
      mutations while their parents carried corresponding heterozygous GJB2 mutations.
      The probands from family 5-8 and the deaf father from family 8 were found to
      carry compound SLC26A4 mutations while their parents and the mother from family 8
      carried a single SLC26A4 mutation. Prenatal testing showed that the fetuses from
      family 1, 5, 8 only carried the paternal mutation and the fetuses from family 2,
      3, 6 didn't carry any GJB2 or SLC26A4 mutations. The new born babies from these
      six families all had normal hearing revealed by new born hearing screening.
      However, the fetuses from family 4,7 carried the same mutations with probands in
      each family. The parents from family 4, 7 decide to terminate pregnancy.
      CONCLUSION: Prenatal diagnosis assisted by genetic testing can provide efficient
      information about hearing condition of their offsprings.

PMID- 18051564
TI  - [Primary investigation of central auditory function in patients with temporal
      lobe epilepsy].
AB  - OBJECTIVE: To investigate the function of central auditory, Speech-perception-in
      noise test (SPIN test) was used to assess that whether temporal lobe epilepsy
      patients have central auditory processing disorders. METHODS: Four audiological
      test were performed in 9 patients with temporal lobe epilepsy and 19 age-matched
      normal hearing persons as controls, which include pure tone audiometry, acoustic
      immittance measurement, ABR (auditory brainstem response) and SPIN test. All the
      temporal lobe epilepsy patients were performed by CT or MRI and diagnosed by the
      neurologists prior to the test. The testing materials of speech and noise in SPIN
      test was recorded in independent tracks and the S/N was identified by -25 dB by
      pre-experiment. In the test, every words were read twice and both the results
      were recorded. RESULTS: In the ABR test, only wave V latency showed longer values
      in the left ear, other waves like I, III and inter-peak intervals had'nt shown
      significant statistical differences in both ears of temporal lobe epilepsy
      patients. However, in the SPIN test, there's no significant statistical
      differences in both left and right ears of the controls by the first-time hearing
      (P = 0.107), and the differences showed by the second-time hearing (P = 0.048);
      but in the comparison of both ears in temporal lobe epilepsy patients, both time
      of hearing showed no significant statistical differences with P = 0.174 and P =
      0.163. In additional, the SPIN recognition score of the temporal lobe epilepsy
      patients, whether in the fist or second time hearing, whether in the monaural or
      binaural models, presented significant statistical differences compared to the
      controls (P = 0.000). CONCLUSIONS: There was no statistically significant
      difference in pure tone audiometry and ABR test for all the groups. But the
      speech recognition score obtained from SPIN test of tempol lobe epilepsy patients
      is lower than the normal persons, which has statistically significant difference.
      (P < 0.001) Then we can come to the conclusion that Temporal lobe epilepsy
      patients had central auditory dysfunctions and SPIN test is a sensitive way to
      assess this abnormal.

PMID- 18051565
TI  - [Retrospective analysis of the effect of intranasal endoscopic resection of
      olfactory neuroblastoma].
AB  - OBJECTIVE: To investigate the effectiveness of intranasal endoscopic resection of
      olfactory neuroblastoma and the significance of assistant radiotherapy. METHODS:
      Six patients (4 men and 2 women) ranging in age from 9-68 years (median age, 48
      years) with olfactory neuroblastoma treated endoscopically at the Third
      Affiliated Hospital of SUN Yat-sen University between August 2001 and September
      2005 were retrospectively analyzed. The Kadish clinical stage was determined for
      all six cases, two cases with stage B, and 4 with stage C. The duration of
      endoscopic follow-up ranged from fourteen months to sixty three months. RESULTS:
      The tumor in five patients was completely excised including one case underwent
      craniotomy firstly and one case underwent neck dissection and the another case
      had her tumor subtotally resected. Five cases underwent assistant radiotherapy
      after operation without any evidence of recurrence so far, while the other one
      (Kadish stage B, tumor totally resection), who had no radiotherapy after first
      procedure, died from local recurrence and cerebellar metastasis 31 months after
      operation. The medium survival duration was 44.5 months. CONCLUSIONS: With simple
      approach, excellent visualization, a less operative invasiveness and no scar on
      face, the endoscopic approach appears to be the method of choice for the
      treatment of olfactory neuroblastoma. But it was necessary for good prognosis to
      combine with radiotherapy after operation.

PMID- 18051566
TI  - [CT evolution of nasal steroid management of chronic rhinosinusitis].
AB  - OBJECTIVE: To evaluate the efficacy of topical steroid treatment of nonpolypoid
      chronic sinusitis. METHODS: Two cohorts of adult and children with nonpolypoid
      chronic sinusitis were investigated. The first cohort consisted of 11 pediatric
      patients [mean age, (11.8 +/- 3.2) years] with a mean Lund score of 10.3 +/- 5.7
      (x +/- s). The second cohort consisted of 13 adult patients [mean age, (36.7 +/-
      11.0) years] with a mean Lund score of 12.2 +/- 5.7. The mean duration of the
      nasal budesonide (Rhinocort) treatment was (7.5 +/- 3.2) weeks for adult patients
      (256 microg/d) and (7.0 +/- 3.4) weeks for pediatric patients (128 microg/d).
      Each Lund score and the patient's assessment of nasal symptoms were evaluated
      after treatment. RESULTS: The average Lund score was significantly decreased to
      6.5 -/+ 7.5 (t = 3.82, P < 0.01) in adult patients and to 2.6 +/- 3.7 (t = 5.08,
      P < 0.01) in pediatric patients after treatment. Thirty-eight percent of the
      adult patients and 73% of the pediatric patients were cured on CT images. The
      patient's self-assessment of efficacy was positively correlated with pretreatment
      Lund score in adult patients (r = 0.676, P < 0.05), but not so in pediatric
      patients. CONCLUSIONS: These findings demonstrate that most of patients with
      nonpolypoid chronic sinus did well with topical steroid treatment. Therefore,
      surgery was required in few patients.

PMID- 18051567
TI  - [Treatment experience of tracheal stenosis from endotracheal granuloma forming
      after tracheostomy].

PMID- 18051568
TI  - [Surgical management of tumor in the conjunctive area among neck, thorax and
      axilla].
AB  - OBJECTIVE: To study the surgical management of tumors in the conjunctive area
      among the neck, thorax and axilla and its efficacy. METHODS: From Oct. 1999 to
      March 2006, eleven cases with benign tumors in the area between the neck, thorax
      and axilla were collected and analysed. Among them, five neurilemmoma, three
      neurofibroma, two chondroma and one meningioma, respectively. CT scans showed
      that the neck, thorax and axilla were affected simultaneously more or less. In
      this group, direct invasion to the vertebra was found in 4 cases, and spinal
      compression in one patient. After the disarticulation and displacement of the
      clavicle, the tumor was removed with the structures of importance in the neck,
      thorax and axilla under direct views. A bypass was constructed between the
      axillary vein and the medial end of the subclavian vein. RESULTS: All these
      tumors were completely removed, injury of vertebral artery was encounter in two
      cases, and immediate repair was successfully carried out. No other serious
      complications were found in this group. During the follow-up period from 3 months
      to 3 years and 5 months, local recurrence was found in no patient. CONCLUSIONS:
      Benign tumors in the area between neck, thorax and axilla could be successfully
      dissected and removed with displacement of the medial portion of the clavicle.

PMID- 18051569
TI  - [Parathyroid adenoma complicating laryngeal obstruction: report of a case].

PMID- 18051570
TI  - [Prevention of facial nerve paralysis induced by herpes simplex virus type 1 (HSV
      1) in mouse and establishment of a relapse model induced by reactivation of
      latent HSV-1].
AB  - OBJECTIVE: To establish an animal model of Bell's palsy induced by the
      reactivation of latent herpes simplex virus type 1 (HSV-1), and observe the
      effect of interferon and IgG on the facial nerve paralysis induced by HSV-1
      infection. METHODS Totally 64 four-week-old female Balb/c mice weighted 16-18
      gram were selected. Using scratching the surface of bilateral auricles by a 26
      gauge needle, 25 microl HSV-1 with a titer of 6.7 x 10(8) PFU/ml was inoculated
      into the left auricle and the same volume of PBS was placed in the right in order
      to develop a mouse model of latent HSV-1. In this study, interferon and IgG
      administration were performed before and after facial nerve paralysis and
      continued for 3 days. Controls were given normal sodium instead of interferon and
      IgG, and the incidence and duration of facial nerve paralysis were compared in
      the groups interferon and IgG and control. Ciclosporin was given to the mice
      eight weeks after recovery from facial nerve paralysis caused by inoculation with
      HSV-1. The HSV-1 DNA in bilateral facial nerve and bilateral trigeminal ganglion
      after the treatment were examined with polymerase chain reaction (PCR) analysis.
      RESULTS There were 10 mice of facial nerve paralysis in the first group. The
      incidence of facial nerve paralysis was 50% and the duration of facial nerve
      paralysis was (7.2 +/- 2.2) days. There were 6 mice of facial nerve paralysis in
      the second group. The incidence of facial nerve paralysis was 30% and the
      duration of facial nerve paralysis was (4.5 +/- 1.8) days. There were 16 mice of
      facial nerve paralysis in the control group. The incidence of facial nerve
      paralysis was 67% and the duration of facial nerve paralysis was (8.9 +/-2.6)
      days. IgG didn't reduce the incidence and duration of facial nerve paralysis by
      statistics analysis (P > 0.05), but interferon reduced the incidence and duration
      of facial nerve paralysis (P < 0.05). After administration of ciclosporin, 3/28
      of mice developed facial nerve paralysis. The HSV-1 DNA was detected from facial
      nerve of all the mice of facial palsy. No facial palsy was observed in mice in
      which no HSV-1 DNA was detected from facial nerve. CONCLUSIONS: Facial nerve
      paralysis might be caused by reactivation of latent HSV-1, and the reactivation
      might be related with immunosuppression. Administration of interferon reduces the
      incidence and duration of facial nerve paralysis. Administration of IgG can't
      reduced the incidence and duration of facial nerve paralysis.

PMID- 18051571
TI  - [Expression and clinical significance of Endostatin, vascular endothelial growth
      factor and fibroblast growth factor basic-2 in laryngeal carcinoma].
AB  - OBJECTIVE: To evaluate the expression and clinical significance of Endostatin,
      vascular endothelial growth factor (VEGF) and fibroblast growth factor basic-2
      (FGF-2) in the laryngeal squamous cell carcinoma (LSCC). METHODS: The expression
      of Endostatin, VEGF and FGF-2 in 50 specimens of LSCC, 40 specimens of para
      carcinoma and 10 specimens of normal laryngeal tissues were examined by Flow
      cytometry. RESULTS: Compared with para-carcinoma and normal laryngeal tissues,
      the expression level and positive rate of Endostatin, VEGF, FGF-2 in LSCC were
      different in statistics (P < 0.05); the expression level and positive rate of
      endostatin, VEGF, FGF-2 in LSCC are obviously higher than those in para-carcinoma
      and normal laryngeal tissues. The expression level and positive rate of
      Endostatin, VEGF, FGF-2 were no difference in statistics between para-carcinoma
      and normal laryngeal tissues (P > 0.05). The expression level and positive rate
      of Endostatin, VEGF, FGF-2 in LSCC were associated with lymphoid metastasis and
      clinical stage, not associated with age, sex and clinical group. CONCLUSIONS:
      Endostatin, VEGF and FGF-2 play important role in the incidence, development and
      prognosis of the LSCC.

PMID- 18051572
TI  - [One case of pleomorphic adenoma of the larynx].

PMID- 18051573
TI  - [Investigation of CD133 as putative marker of tumor-initiating cell in laryngeal
      carcinoma].
AB  - OBJECTIVE: To detect the expression of CD133 in human established larynx tumors
      cell line, Hep-2 cell line and observe tumorigenicity of CD133(+) tumorigenic
      cells, CD133(-) tumorigenic cells and unsorted Hep-2 cells in vivo. The marker of
      cancer stem cells in Hep-2 cell line was explored. METHODS: Flow cytometry was
      used to detect the expression of putative tumor-initiating cell marker CD133 in
      Hep-2 cell line. The immunomagnetic beads separation was applied to purify CD133
      positive cells. CD133(+) tumor cells , CD133(-) tumor cells and unsorted Hep-2
      cells were injected to severe combined immune deficiency mice individually to
      observe their ability of forming new tumors. To determine whether the difference
      in tumorigenicity in subpopulation of Hep-2 cells was due to differences in cell
      growth activity and cell cycle. The growth of sorted cells in vitro was observed
      with HE stain and analyzed cell cycle of CD133(+) cells and unsorted cells by
      flow cytometry. RESULTS: Only a small proportion (3.15 +/- 0.83)% of cells in Hep
      2 cell line express CD133. Both unsorted cells and sorted cells were all
      consistent with the character of malignant tumor. Comparison of the cell cycle
      status of sorted and unsorted cancer cells after magnetic sorting revealed that
      both cells exhibited a similar cell cycle distribution. In 20 injection sites, 16
      sites contained tumor in CD133(+) group, whereas only 10 sites in unsorted group,
      7 sites in CD133(-) group contained tumor. Compared with CD133(-) group (X2 =
      8.286, P = 0.004) and unsorted group (X2 = 3.956, P = 0.047), CD133 positive
      cells possessed a marked capacity for giving rise to new tumors in vivo.
      CONCLUSIONS: CD133 is one of makers for cancer stem cell in human larynx tumors,
      Hep-2 cell line. Identification of it provides a powerful tool to investigate the
      tumorigenic process in the larynx and to develop therapies targeted to the tumor
      initiating cell.

PMID- 18051574
TI  - [In vivo study on the tumor-suppressing effects of VP3 gene on nasopharyngeal
      carcinoma transplanted tumor].

PMID- 18051575
TI  - [Correlation between the expression of NF-kappaB and the T helper cell
      predominant differentiation in a rat model of otitis media with effusion].

PMID- 18051576
TI  - [Applied anatomy about operation on labyrinthine segment of facial nerve via
      middle cranial fossa approach].

PMID- 18051577
TI  - [Reconstruction of maxillary defects by distraction osteogenesis of zygoma and
      free fibula composite flap].

PMID- 18051578
TI  - [Congenitally malformed external-middle ear accompanied by cholesteatoma in
      temporal bone in a patient].

PMID- 18051579
TI  - [Accessory auricle in the nasopharynx in a case].

PMID- 18051580
TI  - [Nasal mucus and nasal inflammation].

PMID- 18051581
TI  - [Allergen-specific subcutaneous immunotherapy for allergic rhinitis].

PMID- 18051582
TI  - [The summary of 5th international conference on newborn hearing screening].

PMID- 18051583
TI  - Commemorating the 125th anniversary of the birth of professor Frantisek Burian
      (17.9.1881 - 15.10.1965).

PMID- 18051584
TI  - Grafting posterior tibial nerve with ipsilateral sural nerve cables in leg
      replantation--a common sense approach.
AB  - In a leg replantation requiring grafting of the posterior tibial nerve, the
      benefits of utilization of the ipsilateral sural nerve are shown. Sparing the
      other leg for obtaining nerve graft and using the incision to harvest the sural
      nerve for achieving fasciotomies minimizes the therapy trauma and helps to
      accomplish early rehabilitation. The simplicity and effectiveness of the
      procedure are discussed in context with peripheral nerve reconstructions
      requiring nerve grafts.

PMID- 18051585
TI  - Bilateral cheek-to-nose advancement flap: an alternative to the paramedian
      forehead flap for reconstruction of the nose.
AB  - Skin cancer on the nose is commonly treated with surgical excision resulting in
      defects that require closure. The surgeon is faced with many reconstructive
      options. The paramedian forehead flap is one commonly used technique. In this
      study we describe the bilateral cheek-to-nose advancement flap as an alternative
      to the paramedian forehead flap in patients with strong nasolabial folds and
      prominent cheek tissue laxity, who require closure of MOHS surgery defects on the
      nasal dorsum and sidewall. Twelve patients were treated with the latter flap and
      evaluated after 2 weeks and 6 months. The patients' subjective and the surgeons'
      objective evaluation after 6 months were either completely satisfied or
      satisfied. The bilateral cheek-to-nose advancement flap is a reliable tool in the
      interventional portfolio of the reconstructive surgeon.

PMID- 18051586
TI  - Case series: variations in the embryology of congenital midline cervical clefts.
AB  - Congenital midline cervical clefts (CMCC) is a clinical diagnosis and represents
      a spectrum of rare developmental anomalies. Fewer than 100 cases have been
      reported overall, the first being described by Bailey in 1924 (1). It is not a
      true cleft because it does not include a gap between adjacent skin flaps. It is
      thought to represent a failure of midline fusion of the branchial arches although
      this is controversial. It is a clinical diagnosis and presents at birth with a
      ventral midline defect of the skin of the neck. This consists of a skin tag
      (nipple-like projection), an atrophic mucosal surface and a caudal sinus. It may
      be associated with a subcutaneous fibrous cord, which can cause a vertical
      midline tethering restricting cervical extension. Associated defects may be a
      median cleft of the mandible, tongue and lower lip. There may be an associated
      delay in mandibular development and hypoplasia or absence of neck structures such
      as the hyoid bone. Associated thyroglossal and bronchogenic cysts may occur as
      well as defects in other parts of the body such as a sternal cleft (2). CMCC has
      been previously reported in the literature as being of a branchial origin,
      however a review of the histology of previous cases suggests a combined branchial
      and bronchogenic component (2-6). We report on two cases that presented with the
      clinical picture of a classical CMCC. Our first case appears to have a
      bronchogenic origin with possible branchial components and the second case
      appears to be solely branchial in origin. There is much debate as to the
      embryology of this clinical entity; we shall endeavour to address the main
      theories.

PMID- 18051587
TI  - Vacuum-assisted closure (VAC) therapy in the management of digital pulp defects.
AB  - Vacuum-assisted closure (VAC) therapy is a relatively new technique in the field
      of wound management. It has been increasingly used in treating various types of
      open wounds with effective results and minimal adverse effects. Digital injuries
      can occasionally be problematic. We report a new application of vacuum-assisted
      closure therapy in treating digital pulp defects.

PMID- 18051588
TI  - Unexpected ulnar nerve schwannoma. The reasonable risk of misdiagnosis.
AB  - Peripheral nerve tumors are rare clinical entities that can present with mild
      symptoms and no neurological deficit. The authors describe one case of
      asymptomatic schwannoma of the ulnar nerve in a 64-year-old man. The mass was
      associated with mild and sporadic discomfort due to the mass size; the clinical
      neurological examination was not conclusive, with Tinel's sign negative; surgery
      confirmed the nervous origin of the tumor and the histopathologic exam confirmed
      the diagnosis of schwannoma. These tumors are difficult to diagnose clinically
      and have often been confused with other benign tumors such as lipomas,
      hemangiomas, synovial cysts, neurofibromas, etc. Clinical care is important to
      prevent, during the surgery, the unfortunate resection of the nerve; all too
      frequently this diagnosis is made intraoperatively or postoperatively with the
      potential to compromise the outcome of the treatment. An appropriate degree of
      awareness is necessary for the inclusion of peripheral nerve tumors as a
      differential diagnosis of an upper extremity mass.

PMID- 18051589
TI  - Cancer chemopreventive effects of lactic acid bacteria.
AB  - Lactic acid bacteria (LAB) provide several potential health and nutritional
      benefits, including improving the nutritional value of food, controlling serum
      cholesterol levels, and controlling some types of cancer. Numerous in vitro, in
      vivo, human, and epidemiological studies have provided evidence of the
      chemopreventive effects of LAB on colon, bladder, liver, breast, and gastric
      cancers. These effects act via diverse mechanisms, including alteration of the
      gastrointestinal microflora, enhancement of the host's immune response, and
      antioxidative and antiproliferative activities. This review discusses the recent
      progresses on the chemopreventive effects of LAB on specific cancer types and the
      underlying molecular mechanisms.

PMID- 18051590
TI  - Analysis of factors affecting the periplasmic production of recombinant proteins
      in Escherichia coli.
AB  - Five fusion proteins between Z domains derived from Staphylococcal Protein A and
      Green Fluorescent Protein or Human Proinsulin were produced on the periplasm of
      Escherichia coli. The effects of the molecular weight and amino acid composition
      of the translocated peptide, culture medium composition, and growth phase of the
      bacterial culture were analyzed regarding the expression and periplasmic
      secretion of the recombinant proteins. It was found that secretion was not
      affected by the size of the translocated peptide (17-42 kDa) and that the highest
      periplasmic production values were obtained on the exponential phase of growth.
      Moreover, the highest periplasmic values were obtained in minimal medium, showing
      the relevance of the culture medium composition on secretion. In silico
      prediction analysis suggested that with respect to the five proteins used in this
      study, those that are prone to form alpha-helix structures are more translocated
      to the periplasm.

PMID- 18051591
TI  - Critical factors to high thermostability of an alpha-amylase from
      hyperthermophilic archaeon Thermococcus onnurineus NA1.
AB  - Genomic analysis of a hyperthermophilic archaeon, Thermococcus onnurineus NA1
      [1], revealed the presence of an open reading frame consisting of 1,377 bp
      similar to alpha-amylases from Thermococcales, encoding a 458-residue polypeptide
      containing a putative 25-residue signal peptide. The mature form of the alpha
      amylase was cloned and the recombinant enzyme was characterized. The optimum
      activity of the enzyme occurred at 80 degrees C and pH 5.5. The enzyme showed a
      liquefying activity, hydrolyzing maltooligosaccharides, amylopectin, and starch
      to produce mainly maltose (G2) to maltoheptaose (G7), but not pullulan and
      cyclodextrin. Surprisingly, the enzyme was not highly thermostable, with half
      life (t(1/2)) values of 10 min at 90 degrees C, despite the high similarity to
      alpha-amylases from Pyrococcus. Factors affecting the thermostability were
      considered to enhance the thermostability. The presence of Ca2+ seemed to be
      critical, significantly changing t(1/2) at 90 degrees C to 153 min by the
      addition of 0.5 mM Ca2+. On the other hand, the thermostability was not enhanced
      by the addition of Zn2+ or other divalent metals, irrespective of the
      concentration. The mutagenetic study showed that the recovery of zinc-binding
      residues (His175 and Cys189) enhanced the thermostability, indicating that the
      residues involved in metal binding is very critical for the thermostability.

PMID- 18051592
TI  - Analysis of active center in hyperthermophilic cellulase from Pyrococcus
      horikoshii.
AB  - A hyperthermostable endoglucanase from Pyrococcus horikoshii with the capability
      of hydrolyzing crystalline cellulose was analyzed. A protein engineering study
      was carried out to obtain a reduced-size mutant. Five amino acid residues at both
      the N- and C-terminus were found to be removable without any loss of activity or
      thermal stability. Site-directed mutagenesis was also performed on R102, N200,
      E201, H297, Y299, E342, and W377, residues possibly involved in the active center
      or in the recognition and binding of a cellulose substrate. The activity of the
      resulting mutants was considerably decreased, confirming that the mutated
      residues were all important for activity. A reduced-size enzyme, as active as the
      wild-type endoglucanase, was successfully obtained, plus the residues critical
      for its activity and specificity were confirmed. Consequently, an engineered
      enzyme with a reduced size was obtained, and the amino acids essential for
      activity were confirmed by site-directed mutagenesis and comparison with a known
      three-dimensional structure.

PMID- 18051593
TI  - Detection of nitrate/nitrite bioavailability in wastewater using a luxCDABE-based
      Klebsiella oxytoca bioluminescent bioreporter.
AB  - In the present study, we have constructed a bioluminescent bioreporter for the
      assessment of nitrate/nitrite bioavailability in wastewater. Specifically, an
      approximately 500-bp DNA fragment containing a nitrate/nitrite-activated nasR
      like promoter (regulating expression of genes encoding nitrite reductase in the
      genus Klebsiella) was fused upstream of the Vibrio fischeri luxCDABE gene
      cassette in a modified mini-Tn5 vector. Characterization of this strain,
      designated W6-1, yielded dose-dependent increased bioluminescence coincident with
      increased nitrate, nitrite, and ammonium added to the growth medium from 1 to 11
      ppm. Bioluminescence in response to nitrogen species addition was light dependent
      up to 10, 7, and 8 ppm with nitrate, nitrite, and ammonium, respectively. This
      response was linear in the range from 1 to 8 ppm for nitrate (R2 = 0.98), 1 to 6
      ppm for nitrite (R2 = 0.99), and 1 to 7 ppm for ammonium (R2 = 0.99). A
      significant bioluminescent response was also recorded when strain W6-1 was
      incubated with slurries from aged, nitrate/nitrite contaminated wastewater. Thus,
      bioreporter strain W6-1 can be used to elucidate factors that constrain the use
      of nitrate/nitrite in wastewaters.

PMID- 18051594
TI  - Evaluation of arabinofuranosidase and xylanase activities of Geobacillus spp.
      isolated from some hot springs in Turkey.
AB  - Some hot springs located in the west of Turkey were investigated with respect to
      the presence of thermophilic microorganisms. Based on phenotyping characteristics
      and 16S rRNA gene sequence analysis, 16 of the isolates belonged to the genus
      Geobacillus and grew optimally at about 60 degrees C on nutrient agar. 16S rRNA
      gene sequence analysis showed that these isolates resembled Geobacillus species
      by > or = 97%, but SDS-PAGE profiles of these 16 isolates differ from some of the
      other species of the genus Geobacillus. However, it is also known that analysis
      of 16S rRNA gene sequences may be insufficient to distinguish between some
      species. It is proposed that recN sequence comparisons could accurately measure
      genome similarities for the Geobacillus genus. Based on recN sequence analysis,
      isolates 11, IT3, and 12 are strains of G stearothermophilus; isolate 14.3 is a
      strain of G thermodenitrificans; isolates 9.1, IT4.1, and 4.5 are uncertain and
      it is required to make further analysis. The presence of xylanase and
      arabinofuranosidase activities, and their optimum temperature and pH were also
      investigated. These results showed that 7 of the strains have both xylanase and
      arabinofuranosidase activities, 4 of them has only xylanase, and the remaning 5
      strains have neither of these activities. The isolates 9.1, 7.1, and 3.3 have the
      highest temperature optima (80 degrees C), and 7.2, 9.1, AO4, 9.2, and AO17 have
      the highest pH optima (pH 8) of xylanase. Isolates 7.2, AO4, AC15, and 12 have
      optimum arabinofuranosidase activities at 75 degrees C, and only isolate AC 15
      has the lowest pH of 5.5.

PMID- 18051595
TI  - Purification, characterization, and cloning of fibrinolytic metalloprotease from
      Pleurotus ostreatus mycelia.
AB  - A fibrinolytic protease (PoFE) was purified from the cultured mycelia of the
      edible oyster mushroom Pleurotus ostreatus, using a combination of various
      chromatographies. The purification protocol resulted in an 876-fold purification
      of the enzyme, with a final yield of 6.5%. The apparent molecular mass of the
      purified enzyme was estimated to be 32 kDa by SDS-PAGE, fibrin-zymography, and
      size exclusion using FPLC. The optimal reaction pH value and temperature were pH
      6.5 and 35 degrees C, respectively. PoFE effectively hydrolyzed fibrinogen,
      preferentially digesting the A alpha-chain and the B beta-chain over the gamma
      chain. Enzyme activity was enhanced by the addition of Ca2+, Zn2+, and Mg2+ ions.
      Furthermore, PoFE activity was potently inhibited by EDTA, and it was found to
      exhibit a higher specificity for the chromogenic substrate S-2586 for
      chymotrypsin, indicating that the enzyme is a chymotrypsin-like metalloprotease.
      The first 19 amino acid residues of the N-terminal sequence were
      ALRKGGAAALNIYSVGFTS, which is extremely similar to the metalloprotease purified
      from the fruiting body of P. ostreatus. In addition, we cloned the PoFE protein,
      encoding gene, and its nucleotide sequence was determined. The cDNA of cloned
      PoFE is 867 nucleotides long and consists of an open reading frame encoding 288
      amino acid residues. Its cDNA showed a high degree of homology with PoMEP from P.
      ostreatus fruiting body. The mycelia of P. ostreatus may thus represent a
      potential source of new therapeutic agents to treat thrombosis.

PMID- 18051596
TI  - Shelf-life extension of fresh-cut iceberg lettuce (Lactuca sativa L) by different
      antimicrobial films.
AB  - This study was conducted to investigate the antibacterial activity and shelf-life
      extension effect of iceberg lettuce packed in BN/PE film. The BN/PE film has a
      strong microbial suppression effect on pathogenic bacteria such as Escherichia
      coli, Salmonella enteritidis, and S. typhimurium. The number of psychrophiles and
      mesophiles during 5 days of cold storage of fresh-cut iceberg lettuce at 10
      degrees C packaged in BN/PE film was strictly suppressed in comparison with other
      tested films (OPP, PE, and PET film). When fresh processed iceberg lettuce was
      processed and stored under the current conditions, the shelf-life of the product
      was longer than 5 days in the BN/PE film package, whereas the shelf-life when
      using the other films tested, PE, OPP and PET, was no longer than 3-4 days. The
      decay rates of the iceberg lettuce packed in the BN/PE film was maintained at
      29.8 +/- 2.1% on the 5th day of preservation. The samples packed in BN/PE film
      maintained an excellent visual quality during the 3 days of storage without
      significant differences in comparison with the initial visual quality. No
      browning was observed in the samples packed in BN/PE film for up to 3 days. The
      texture of shredded iceberg lettuce packaged in BN/PE film remained unchanged up
      to 3 days, and then a moderate decrease in texture was observed after 4 days of
      storage. In addition, the overall acceptability of fresh-cut iceberg lettuce
      packaged in BN/PE film did not change for up to 3 days, whereas the samples
      packaged in the other films were inedible by 3 days of storage. In conclusion,
      the shelf-life of fresh-cut iceberg lettuce packaged in the BN/PE film was
      extended to more than 5 days at 10 degres C, whereas that in the other films was
      2 days at 10 degrees C. Therefore, the shelf-life extension effect of the fresh
      cut iceberg lettuce in BN/PE film packaging was very effective compared with the
      other films tested.

PMID- 18051597
TI  - Characterization and action patterns of two beta-1,4-glucanases purified from
      cellulomonas uda CS1-1.
AB  - Two beta-1,4-glucanases (DI and DIII fractions) were purified to homogeneity from
      the culture filtrate of a cellulolytic bacteria, Cellulomonas sp. CS1-1, which
      was classified as a novel species belonging to Cellulomonas uda based on
      chemotaxanomic and phylogenetic analyses. The molecular mass was estimated as
      50,000 Da and 52,000 Da for DI and DIII, respectively. Moreover, DIII was
      identified as a glycoprotein with a pI of 3.8, and DI was identified as a non
      glycoprotein with a pI of 5.3. When comparing the ratio of the CMC-saccharifying
      activity and CMC-liquefying activity, DI exhibited a steep slope, characteristic
      of an endoglucanase, whereas DIII exhibited a low slope, characteristic of an
      exoglucanase. The substrate specificity of the purified enzymes revealed that DI
      efficiently hydrolyzed CMC as well as xylan, whereas DIII exhibited a high
      activity on microcrystalline celluloses, such as Sigmacells. A comparison of the
      hydrolysis patterns for pNP-glucosides (DP 2-5) using an HPLC analysis
      demonstrated that the halosidic bond 3 from the nonreducing end was the
      preferential cleavage site for DI, whereas bond 2, from which the cellobiose unit
      is split off, was the preferential cleavage site for DIII. The partial N-terminal
      amino acid sequences for the purified enzymes were 1Ala-Gly-Ser-Thr-Leu-Gln-Ala
      Ala-Ala-Ser-Glu-Ser-Gly-Arg-Tyr15- for DI and 1Ala-Asp-Ser-Asp-Phe-Asn-Leu-Tyr
      Val-Ala-Glu-Asn-Ala-Met-Lys15- for DIII. The apparent sequences exhibited high
      sequence similarities with other bacterial beta-1,4-glucanases as well as beta
      1,4-xylanases.

PMID- 18051598
TI  - Effectiveness of various Pseudomonas spp. and Burkholderia caryophylli containing
      ACC-deaminase for improving growth and yield of wheat (Triticum aestivum L.).
AB  - This study assessed the possible role of different traits in selected plant
      growth-promoting rhizobacteria (PGPR) for improving wheat growth and yield under
      natural conditions. Rhizobacteria exhibiting 1-aminocyclopropane-1-carboxylate
      (ACC)-deaminase activity were isolated and screened for their growth-promoting
      activity in wheat under axenic conditions. Five isolates belonging to Pseudomonas
      and one Burkholderia caryophylli isolate that showed promising performances under
      axenic conditions were selected and characterized for in vitro ACC-deaminase
      activity, chitinase activity, auxin production, P solubilization, and root
      colonization. These isolates were then used as inocula for wheat cultivated under
      natural conditions in pot and/or field trials. Significant increases in root
      elongation, root weight, tillers per pot, 1,000-grain weight, and grain and straw
      yields were observed in response to inoculation with PGPR in the pot trials.
      Inoculation with these PGPR was also effective under field conditions and
      increased the wheat growth and yield significantly. However, the efficacy of the
      strains was inconsistent under the axenic, pot, and field conditions.
      Pseudomonasfluorescens (ACC50), which exhibited a relatively high in vitro ACC
      deaminase activity, chitinase activity, auxin production, and P solubilization
      and more intensive root colonization, was the most efficient isolate under the
      field conditions. Therefore, these results demonstrated that ACC-deaminase
      activity is an efficient parameter for the selection of promising PGPR under
      axenic conditions. However, additional traits of PGPR, including auxin
      production, chitinase activity, P solubilization, and root colonization, are also
      important for selecting PGPR as biofertilizers.

PMID- 18051599
TI  - In vitro evolution of lipase B from Candida antarctica using surface display in
      hansenula polymorpha.
AB  - ALipase B from Candida antarctica (CalB) displayed on the cell surface of H.
      polymorpha has been functionally improved for catalytic activity by molecular
      evolution. CalB was displayed on the cell surface by fusing to a cell-wall anchor
      motif (CwpF). A library of CalB mutants was constructed by in vivo recombination
      in H. polymorpha. Several mutants with increased whole-cell CalB activity were
      acquired from screening seven thousand transformants. The two independent mutants
      CalB10 and CalB14 showed an approximately 5 times greater whole-cell activity
      than the wild-type. When these mutants were made as a soluble form, CalB 10
      showed 6 times greater activity and CalB14 showed an 11 times greater activity
      compared with the wild-type. Sequence analyses of mutant CALB genes revealed
      amino acid substitutions of Leu278Pro in CalB10 and Leu278Pro/Leu219Gln in
      CalB14. The substituted Pro278 in both mutants was located near the proline site
      of the alpha10 helix. This mutation was assumed to induce a conformational change
      in the alpha10 helix and increased the k(cat) value of mutant CalB approximately
      6 times. Site-directed mutagenized CalB, LQ (Leu219Gln) was secreted into the
      culture supernatant at an amount of approximately 3 times more without an
      increase in the CalB transcript level, compared with the wild-type.

PMID- 18051600
TI  - Development of a protein secretion system with the application of sec-dependent
      protein secretion components.
AB  - In order to induce high levels of protein secretion, we have constructed a
      recombinant plasmid, designated pBP244, into which was incorporated key
      components of the type-II Sec-dependent secretion system, including LepB (signal
      peptidase), SecA (ATPase), and SecB (chaperone). The biological activities of the
      LepB, SecA, and SecB components expressed from genes harbored by pBP244 appeared
      to play their normal roles. In order to evaluate the protein secretion, a pspA
      (Streptococcus pneumoniae surface protein A) gene was cloned into pBP244,
      resulting in pBP438. S. typhimurium harboring pBP438 grown until the stationary
      phase, secreted a higher level of PspA into the culture supernatants than did the
      strain harboring pYA3494. The strain harboring pBP438 secreted a supernatant
      amount 1.71-fold, a periplasmic space amount 1.47-fold, and an outer membrane
      amount 1.49-fold higher than that of pYA3494. S. typhimurium chi8554 kept the
      Asd+ plasmid pBP244 and pBP438 for 60 generations in LB broth harboring DAP,
      thereby indicating that pBP244 and pBP438 were quite stable in the Salmonella
      strain.

PMID- 18051601
TI  - Candicidal action of resveratrol isolated from grapes on human pathogenic yeast
      C. albicans.
AB  - Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring, multi
      biofunctional chemical existing in grapes and various other plants as a
      polyphenol type, and it is one of the best known natural anticancer and
      antiatherosclerosis reagents. In this study, we investigated the antifungal
      action by resveratrol in Candida albicans, which is a human infectious fungi as
      an agent of candidiasis. Resveratrol displayed potent fungicidal activity in an
      energy-dependent manner, without any hemolytic effects against human
      erythrocytes. It was found that the serum-induced mycelial forms, which play a
      crucial role in the pathogenesis of C. albicans during host tissue invasion, were
      disrupted by resveratrol. To understand the correlation between lethal effects
      and resveratrol action, we examined the physiological changes of C. albicans. A
      significant accumulation of intracellular trehalose was induced by stress
      responses to resveratrol action, and a remarkable arrest of cell-cycle processes
      at the S-phase in C. albicans occured. Therefore, the fungicidal effects of
      resveratrol demonstrate that this compound is a potential candidate as an
      antifungal agent in treating infectious diseases by candidal infections.

PMID- 18051603
TI  - Streptochlorin, a marine natural product, inhibits NF-kappaB activation and
      suppresses angiogenesis in vitro.
AB  - Angiogenesis is an essential step in tumor progress and metastasis. Accordingly,
      small molecules that inhibit angiogenesis would appear to be a promising way to
      cure angiogenesis-related diseases, including cancer. In the present study, we
      report that streptochlorin, a small molecule from marine actinomycete, exhibits a
      potent antiangiogenic activity. The compound potently inhibited endothelial cell
      invasion and tube formation stimulated with vascular endothelial cell growth
      factor (VEGF) at low micromolar concentrations where it showed no cytotoxicity to
      the cells. In addition, streptochlorin inhibited TNF-alpha-induced NF-kappaB
      activation in the newly developed cell-based reporter gene assay. These data
      demonstrate that streptochlorin is a new inhibitor of NF-kappaB activation and
      can be a basis for the development of novel anti-angiogenic agents.

PMID- 18051604
TI  - Identification of Pseudomonas aeruginosa genes crucial for hydrogen peroxide
      resistance.
AB  - An opportunistic human pathogen, Pseudomonas aeruginosa, contains the major
      catalase KatA, which is required to cope with oxidative and osmotic stresses. As
      an attempt to uncover the H2O2-dependent regulatory mechanism delineating katA
      gene expression, four prototrophic H2O2-sensitive mutants were isolated from
      about 1,500 TnphoA mutant clones of P. aeruginosa strain PA14. Arbitrary PCR and
      direct cloning of the transposon insertion sites revealed that one insertion is
      located within the katA coding region and two are within the coding region of
      oxyR, which is responsible for transcriptional activation of several antioxidant
      enzyme genes in response to oxidative challenges. The fourth insertion was within
      PA3815 (IscR), which encodes a homolog of the Escherichia coli iron-sulfur
      assembly regulator, IscR. The levels of catalase and SOD activities were
      significantly reduced in the iscR mutant, but not in the oxyR mutant, during the
      normal planktonic culture conditions. These results suggest that both IscR and
      OxyR are required for the optimal resistance to H2O2, which involves the
      expression of multiple antioxidant enzymes including KatA.

PMID- 18051605
TI  - Expression analysis of the csp-like genes from Corynebacterium glutamicum
      encoding homologs of the Escherichia coli major cold-shock protein cspA.
AB  - Three csp-like genes were identified in the Corynebacterium glutamicum genome and
      designated cspA, cspB, and cspA2. The genes cspA and cspA2 encode proteins,
      comprising of 67 amino acid residues, respectively. They share 83% identity with
      each other. Identity of those proteins with Escherichia coli Csp proteins was
      near 50%. The cspB gene encodes a protein composed of 127 amino acids, which has
      40% and 35% sequence identity with CspA and CspA2, respectively, especially at
      its N-terminal region. Analysis of the gene expression profiles was done using
      transcriptional cat fusion, which identified not only active expression of the
      three genes at the physiological growth temperature of 30 degrees C but also
      growth phase-dependent expression with the highest activity at late log phase.
      The promoters of cspA and cspA2 were more active than that of cspB. The
      expression of the two genes increased by 30% after a temperature downshift to 15
      degrees C, and such stimulation was more evident in the late growth phase. In
      addition, the cspA gene appeared to show DNA-binding activity in vivo, and the
      activity increased at lower temperatures. Interestingly, the presence of cspA in
      multicopy hindered the growth of the host C. glutamicum cells at 20 degrees C,
      but not at 30 degrees C. Altogether, these data suggest that cspA, cspB, and
      cspA2 perform functions related to cold shock as well as normal cellular
      physiology. Moreover, CspA and its ortholog CspA2 may perform additional
      functions as a transcriptional regulator.

PMID- 18051606
TI  - Plant growth-promoting potential of endophytic bacteria isolated from roots of
      coastal sand dune plants.
AB  - Endophytic bacteria associated with the roots of coastal sand dune plants were
      isolated, taxonomically characterized, and tested for their plant growth
      promoting activities. Ninety-one endophytic bacterial isolates were collected and
      assigned to 17 different genera of 6 major bacterial phyla based on partial 16S
      rDNA sequence analyses. Gammaproteobacteria represented the majority of the
      isolates (65.9%), and members of Pseudomonas constituted 49.5% of the total
      isolates. When testing for antagonism towards plant pathogenic fungi, 25 strains
      were antagonistic towards Rhizoctonia solani, 57 strains were antagonistic
      towards Pythium ultimum, 53 strains were antagonistic towards Fusarium oxysporum,
      and 41 strains were antagonistic towards Botrytis cinerea. Seven strains were
      shown to produce indole acetic acid (IAA), 33 to produce siderophores, 23 to
      produce protease, 37 to produce pectinase, and 38 to produce chitinase. The
      broadest spectra of activities were observed among the Pseudomonas strains,
      indicating outstanding plant growth-promoting potential. The isolates from C.
      kobomugi and M. sibirica also exhibited good plant growth-promoting potential.
      The correlations among individual plant growth-promoting activities were examined
      using phi coefficients, and the resulting data indicated that the production of
      protease, pectinase, chitinase, and siderophores was highly related.

PMID- 18051607
TI  - Exopolysaccharide production and mycelial growth in an air-lift bioreactor using
      Fomitopsis pinicola.
AB  - For effective exopolysaccharide production and mycelial growth by a liquid
      culture of Fomitopsis pinicola in an air-lift bioreactor, the culture
      temperature, pH, carbon source, nitrogen source, and mineral source were
      initially investigated in a flask. The optimal temperature and pH for mycelial
      growth and exopolysaccharide production were 25degrees C and 6.0, respectively.
      Among the various carbon sources tested, glucose was found to be the most
      suitable carbon source. In particular, the maximum mycelial growth and
      exopolysaccharide production were achieved in 4% glucose. The best nitrogen
      sources were yeast extract and malt extract. The optimal concentrations of yeast
      extract and malt extract were 0.5 and 0.1%, respectively. K2HPO4 and MgSO4 x 7H2O
      were found to be the best mineral sources for mycelial growth and
      exopolysaccharide production. In order to investigate the effect of aeration on
      mycelial growth and exopolysaccharide production in an air-lift bioreactor,
      various aerations were tested for 8 days. The maximum mycelial growth and
      exopolysaccharide production were 7.9 g/l and 2.6 g/l, respectively, at 1.5 vvm
      of aeration. In addition, a batch culture in an air-lift bioreactor was carried
      out for 11 days under the optimal conditions. The maximum mycelial growth was
      10.4 g/l, which was approximately 1.7-fold higher than that of basal medium. The
      exopolysaccharide production was increased with increased culture time. The
      maximum concentration of exopolysaccharide was 4.4 g/l, which was about 3.3-fold
      higher than that of basal medium. These results indicate that exopolysaccharide
      production increased in parallel with the growth of mycelium, and also show that
      product formation is associated with mycelial growth. The developed model in an
      air-lift bioreactor showed good agreement with experimental data and simulated
      results on mycelial growth and exopolysaccharide production in the culture of F
      pinicola.

PMID- 18051608
TI  - Sufflavibacter maritimus gen. nov., sp. nov., novel Flavobacteriaceae bacteria
      isolated from marine environments.
AB  - Four Gram-negative, chemoheterotrophic, nonmotile, yellow-colored strains were
      isolated from the East Sea or from deep-sea sediments of Nankai Trough by
      standard dilution plating. Characterization by polyphasic approaches indicated
      that the four strains are members of the same species. Phylogenetic analyses
      based on 16S rRNA gene sequences revealed that the strains formed a coherent and
      novel genus-level lineage within the family Flavobacteriaceae. The dominant
      cellular fatty acids were i-C15:0, 3-OH i-C17:0, and 2-OH i-C15:0 and/or C16:1
      omega7c. Predominance of 2-OH i-C 15:0 and/or C16:1omega7c clearly differentiated
      the strains from closely related members. The DNA G+C contents ranged 35.1-36.2
      mol%. It is proposed, from the polyphasic evidence, that the strains should be
      placed into a novel genus and species named Sufflavibacter maritimus gen. nov.,
      sp. nov., with strain IMCC 1001T (=KCCM 42359T=NBRC 102039T) as the type strain.

PMID- 18051609
TI  - Engineering and characterization of the isolated C-terminal domain of 5
      enolpyruvylshikimate-3-phosphate (EPSP) synthase.
AB  - 5-Enolpyruvylshikimate-3-phosphate (EPSP) synthase catalyzes the formation of
      EPSP and inorganic phosphate from shikimate-3-phosphate (S3P) and
      phosphoenolpyruvate (PEP) in the biosynthesis of aromatic amino acids. To
      delineate the domain-specific function, we successfully isolated the
      discontinuous C-terminal domain (residues 1-21, linkers, 240-427) of EPSP
      synthase (427 residues) by site-directed mutagenesis. The engineered C-terminal
      domains containing no linker (CTD), or with gly-gly (CTD(GG)) and gly-ser-ser-gly
      (CTD(GSSG)) linkers were purified and characterized as having distinct native
      like secondary and tertiary structures. However, isothermal titration calorimetry
      (ITC), 15N-HSQC, and 31P-NMR revealed that neither its substrate nor inhibitor
      binds the isolated domain. The isolated domain maintained structural integrity,
      but did not function as the half of the full-length protein.

PMID- 18051611
TI  - Acaricidal effects of quinone and its congeners and color alteration of
      Dermatophagoides spp. with quinone.
AB  - Acaricidal activity of the active constituent derived from Pyrus ussuriensis
      fruits against Dermatophagoides farinae and D. pteronyssinus was examined and
      compared with that of the commercial benzyl benzoate. The LD50 value of the ethyl
      acetate fraction obtained from the aqueous extract of P ussuriensis fruits was
      9.51 and 8.59 microg/cm3 against D. farinae and D. pteronyssinus, respectively.
      The active constituent was identified as quinone by spectroscopic analyses. On
      the basis of LD50 values with quinone and its congeners, the compound most toxic
      against D. farinae was quinone (1.19 microg/cm3), followed by quinaldine (1.46),
      benzyl benzoate (9.32), 4-quinolinol (86.55), quinine (89.16), and 2-quinolinol
      (91.13). Against D. pteronyssinus, these were quinone (1.02 microg/ cm3),
      followed by quinaldine (1.29), benzyl benzoate (8.54), 4-quinolinol (78.63),
      quinine (82.33), and 2-quinolinol (86.24). These results indicate that the
      acaricidal activity of the aqueous extracts can be mostly attributed to quinone.
      Quinone was about 7.8 and 8.4 times more toxic than benzyl benzoate against D.
      farinae and D. pteronyssinus. Additionally, quinaldine was about 6.4 and 6.6
      times more toxic than benzyl benzoate against D. farinae and D. pteronyssinus,
      respectively. Furthermore, the skin color of the dust mites was changed from
      colorless-transparent to dark brown-black by the treatment of quinone. These
      results indicate that quinone can be very useful as potential control agents,
      lead compounds, or the indicator of house dust mites.

PMID- 18051610
TI  - Analysis of the stress effects of endocrine disrupting chemicals (EDcs) on
      Escherichia coli.
AB  - In this study, three of the representative EDCs, 17beta-estradiol, bisphenol A,
      and styrene, were employed to find their mode of toxic actions in E. coli. To
      accomplish this, four different stress response genes, recA, katG, fabA, and grpE
      genes, were used as a representative for DNA, oxidative, membrane, or protein
      damage, respectively. The expression levels of these four genes were quantified
      using a real-time RT-PCR after challenge with three different EDCs individually.
      Bisphenol A and styrene caused high-level expression of recA and katG genes,
      respectively, whereas 17beta-estradiol made no significant changes in expression
      of any of those genes. These results lead to the classification of the mode of
      toxic actions of EDCs on E. coli.

PMID- 18051612
TI  - The virulence of Vibrio vulnificus is affected by the cellular level of
      superoxide dismutase activity.
AB  - The virulence of superoxide dismutase (SOD) mutants of Vibrio vulnificus, as
      tested by intraperitoneal injection into mice, decreases in the order of sodC
      mutant, sodA mutant, and sodB mutant lacking CuZnSOD, MnSOD, and FeSOD,
      respectively. The survival of SOD mutants under superoxide stress also decreases
      in the same order. The virulence of soxR mutant, which is unable to induce MnSOD
      in response to superoxide, is similar to that of the sodA mutant, as the survival
      of the soxR mutant under superoxide stress is similar to that of the sodA mutant.
      Consistently, the lowered survival of the soxR mutant is complemented not only
      with soxR but also with sodA. Thus, the virulence of V. vulnificus is
      significantly affected by the cellular level of SOD activity, and an increase in
      SOD level through MnSOD induction by SoxR under superoxide stress is essential
      for virulence.

PMID- 18051613
TI  - Isolation and structure determination of streptochlorin, an antiproliferative
      agent from a marine-derived Streptomyces sp. 04DH110.
AB  - An antiproliferative agent, streptochlorin, was isolated from the fermentation
      broth of a marine actinomycete isolated from marine sediment. Phylogenetic
      analysis of the 16S rRNA gene sequence indicated that the strain belongs to the
      genus Streptomyces. Bioactivity guided fractionation of the culture extract by
      solvent partitioning, ODS open flash chromatography, and reversed-phase HPLC gave
      a pure compound, streptochlorin. Its structure was elucidated by extensive 2D NMR
      and mass spectral analyses. Streptochlorin exhibited significant
      antiproliferative activity against human cultured cell lines.

PMID- 18051614
TI  - [Strengthening parenting competences through primary prevention: one ounce of
      prevention weighs more than one pound of therapy].
AB  - Upon a clarification of the term and main components of parenting competences,
      the present contribution first delineates research-focused aspects and various
      target groups for primary familial prevention. Then, an overview of a selection
      of preventive measures for German speaking countries aiming at strengthening
      parental competences is provided for universal prevention programs including
      available information on the effectiveness of the corresponding programs. Next,
      an account of some meta-analytic findings and cost-benefit analyses concerning
      the relevance of parenting programs is presented. Finally, some desiderata
      concerning the development and evaluation of preventive approaches to
      strengthening parenting competences are briefly addressed.

PMID- 18051615
TI  - [Promoting sensitivity and parenting competencies in teenage mothers].
AB  - Relevant concepts of parenting emphasize biologically oriented behavioral
      tendencies as intuitive parenting that unconsciously guides interaction with the
      infant. They can be violated by risk factors or adverse life conditions and are
      to be perceived in parental problems to cope with the infants' needs and even in
      neglecting and maltreating behavioral displays. In particular high risk groups as
      teenage mothers are affected. Early and preventive intervention efforts promoting
      parent-child relationship seem to be successful to prevent maltreatment and later
      behavioral problems in the child. An attachment-oriented and video-based program
      for intervention with teenage mothers is described. Chances and limits of
      promoting parent-child attachment in teenage mothers are discussed.

PMID- 18051616
TI  - [Promotion of parental competence with triple P].
AB  - Parental competencies have great impact on child development. The concept of
      parental competency is a comprehensive construct, that involves functional and
      dysfunctional rearing behavior as well as evaluation of parental coping with
      challenging rearing situations and self-efficacy of rearing. Enhancing parental
      education is an important challenge on the background of high prevalence rates of
      child behavior problems. In the present randomised controlled study the effects
      of a Triple P parent training on parental competence was examined. 280 families
      were randomly assigned to a training of a control group. After pre-assessment,
      the training group participated in a Triple P parent training. 6 and 12 month
      after pre-assessment, post- and follow-up-1-year-assessments were conducted.
      Mothers in the training group showed significantly increased parental
      competencies compared to the control group. Especially overt functional and
      dysfunctional rearing behavior changed positively. Fathers showed no such change,
      but did often also not participate in the training. The study illustrates that
      parental competence can be promoted through Triple P.

PMID- 18051617
TI  - [17 tips on parenting--which strategies do parents apply?].
AB  - The necessity to make available education support to parents is undisputed
      because of the epidemiology of child behavior problems. Parent trainings are a
      method to increase parenting competence. Triple P as a successful example of a
      parenting and family support program is introduced briefly with his theoretical
      bases, intervention levels, basic principles and education strategies. In
      addition, findings are reported to the effectiveness and consumer satisfaction.
      The present work examines which Triple P-strategies use parents after the
      training in the everyday life. The data come from the project "Zukunft Familie"
      in which the long-term effectiveness of the Triple P-training was examined in a
      controlled study in 280 families. 144 parents took part in the Triple P-group
      training and filled before, directly after the intervention and with 1-year
      follow up questionnaires to the education strategies. The results show that the
      positive education strategies were used for promotiong child development already
      before the training more often as the ideas to managing misbehavior. More than
      90% of the parents, above all, the positive education strategies also practised
      with the 1-year follow-up. In addition, there was a significant decrease by the
      use of the "time out"-strategy.

PMID- 18051618
TI  - [ELTERN-AG--the low threshold school for parents for the early childhood].
AB  - ELTERN-AG is a selective program of primary prevention. It is a low threshold
      program and establishes resources of the parents. The groups are homogeneous
      which means that all families have similar problems. It works with deprived
      parents from the moment when they plan to get a baby up to their child's school
      entry. The concept ELTERN-AG theoretically derives from the need-oriented
      psychological model set up by Epstein (1990) and Grawe (2004) and was modified by
      Armbruster (2006). It assumed, that deprived people are prevented from meeting
      their essential needs, so that they are not able to perceive and meet the
      children's basic needs adequately. ELTERN-AG aims in 20 sessions at the training
      of competences in early education and the strengthening of the parents' self-help
      potentials through empowerment. The results of the 3-year long scientific
      accompanying research show that parents that participated in a course see
      themselves strengthened when dealing with their children, assess in total the
      relationship to children more positively and are more confident when coping with
      problems which occur in connection with their children. During the course parents
      notice a change about themselves which is recognized by mentors as well as
      professional multipliers and is confirmed as positive change.

PMID- 18051619
TI  - [Research and practice. Learning from the results of a study on problems that
      elicit nursing surveillance].

PMID- 18051620
TI  - [Epidemiology of problems related to drugs and devices in nursing homes in
      various regions of Italy].
AB  - The premises, questions and methodological problems of a multicentre study aimed
      at describing the epidemiology of patients' problems that require a nursing
      intervention are described. The main points and methodological challenges are
      presented and discussed: (a.) the choice of focusing on patients cared for in
      Nursing homes and districts because a. they are complex, originate very high
      nursing workload, b. few studies and data from the nursing point of view are
      produced; c. information on everyday care and problems are lacking, d. they are
      marginal populations both in research and organization of care; (b.) the need of
      involving nurses in a surveillance exercise, to increase the attention on
      problems, their causes and potential avoidability, focusing the attention on
      problems related to drugs and devices; (c.) the importance-and challenge- of
      describing what happens in everyday' care, taking in account the variability
      related to contexts and people. The recognition of a problem is, in fact, related
      to factors such as the knowledge of the patient and his/her story, the level of
      knowledge and expertise of the nurse, the attention paid, the context and the
      organization. The main lessons learned are summarised.

PMID- 18051621
TI  - [The safety of drug therapies: strategies and methods for nurses].

PMID- 18051622
TI  - [Condemned to pain].

PMID- 18051602
TI  - Annotation and expression profile analysis of cDNas from the Antarctic diatom
      Chaetoceros neogracile.
AB  - To better understand the gene expression of the cold-adapted polar diatom, we
      conducted a survey of the Chaetoceros neogracile transcriptome by cDNA sequencing
      and expression of interested cDNAs from the Antarctic diatom. A non-normalized
      cDNA library was constructed from the C. neogracile, and a total of 2,500 cDNAs
      were sequenced to generate 1,881 high-quality expressed sequence tags (ESTs)
      (accession numbers EL620615-EL622495). Based on their clustering, we identified
      154 unique clusters comprising 342 ESTs. The remaining 1,540 ESTs did not
      cluster. The number of unique genes identified in the data set is thus estimated
      to be 1,694. Taking advantage of various tools and databases, putative functions
      were assigned to 939 (55.4%) of these genes. Of the remaining 540 (31.9%) unknown
      sequences, 215 (12.7%) appeared to be C. neogracile-specific since they lacked
      any significant sequence similarity to any sequence available in the public
      databases. C. neogracile consisted of a relatively high percentage of genes
      involved in metabolism, genetic information processing, cellular processes,
      defense or stress resistance, photosynthesis, structure, and signal transduction.
      From the ESTs, the expression of these putative C. neogracile genes was
      investigated: fucoxanthin chlorophyll (chl) a,c-binding protein (FCP), ascorbate
      peroxidase (ASP), and heat-shock protein 90 (HSP90). The abundance of ASP and
      HSP90 changed substantially in response to different culture conditions,
      indicating the possible regulation of these genes in C. neogracile.

PMID- 18051623
TI  - [Restraining without coercion].

PMID- 18051624
TI  - [The new challenges of interventions in humanitarian emergencies: working with
      Doctors Without Borders].

PMID- 18051625
TI  - Rigid spine syndrome: vacuolar variant multimodal evoked potentials.
AB  - BACKGROUND: Overt or covert central nervous system (CNS) abnormalities have been
      reported in various primary muscle diseases, including congenital muscular
      dystrophies. PURPOSE: To ascertain by neurophysiologic techniques evidence of CNS
      dysfunction in a relatively large, homogeneous group of patients with the
      "vacuolar variant" of the rigid spine syndrome (RSS). METHODS: Standard evoked
      potential (EP) techniques were used to study the visual, auditory and
      somatosensory pathways in patients with RSS. RESULTS: Abnormal values were
      recorded in 78% (7/9) of patients, specifically of visual pathways (2/9),
      brainstem auditory pathways (2/9), and somatosensory pathways (5/9), and the
      retina (1/9). Abnormal findings were not correlated with clinical measures of
      patient age, disease duration nor degree of weakness. CONCLUSION:
      Electrophysiological studies showed that the CNS is not primarily involved in any
      disease process that underlies this congenital myopathy. There were reasonable
      other explanations for most abnormal measurements.

PMID- 18051626
TI  - Electromyographic validation of the deltoideus (anterior portion) and pectoralis
      major (clavicular portion) muscles in pull-over exercises.
AB  - The electromyographic activity of the deltoideus (anterior portion) and
      pectoralis major (clavicular portion) muscles was analyzed in 24 male volunteers
      in two different modalities of pull-over exercises. The PMC activity varied from
      weak to moderate in both modalities, while the DA activity was moderate in the
      pull-over and strong in the pull-over with bent arms exercises.

PMID- 18051627
TI  - Electromyographic analysis of the arm muscles in "back support" exercises.
AB  - This study aims at quantifying through electromyography the actions of the biceps
      brachii-BB (long head), triceps brachii-TB (long head) and deltoideus-DA
      (clavicular portion) muscles, during the going (G) and return (R) phases in "back
      support" exercises. Surface electrodes were placed at the muscles, according to
      DELAGI (1981). It was used a specific software and a A/D plate to take the
      signals. After being collected, the records were processed resulting in efficient
      values (RMS), were normalized by maximum isometric contraction (MVIC = 100%) and
      statistically analysed using the Friedman, DSM and Wilcox non-parametric tests.
      All the muscles presented electromyographic activity of the movements. The
      triceps brachii was the muscle with higher activity in both phases of the
      movement. It was concluded that the exercise is indicated for the arm muscle
      strength development.

PMID- 18051628
TI  - Changes in soleus motoneuron pool reflex excitability and surface EMG parameters
      during fatiguing low- vs. high-intensity isometric contractions.
AB  - The fatigue-related changes in soleus motoneuron pool reflex excitability and
      surface electromyography (EMG) parameters, and maximal voluntary contraction
      (MVC) force of the plantarflexor (PF) muscles during repeatedly sustained low-
      (30% MVC) vs. high-intensity (70% MVC) isometric contractions were evaluated
      Twelve young men with mean (+/- SE) age of 22.4 +/- 0.3 years participated in two
      fatigue tasks on separate days with at least 1-week interval. The fatigue task
      consisted of three sustained isometric contractions of PF muscles at a target
      force level until exhaustion separated with 2-min pause between contractions. M
      wave (muscle compound action potential) amplitude (M(max)), Hoffmann reflex
      maximal amplitude (H(max)) to M-wave amplitude ratio (H(max)/M(max)), and root
      mean square amplitude (RMS) and median frequency (MF) of EMG power spectrum were
      recorded from the soleus muscle. The M(max) remained constant immediately post
      fatigue and during recovery for low- and high-intensity fatigue tasks, whereas
      H(max)/M(max) was significantly (p < 0.05) reduced only after high-intensity
      fatigue task. The increase in RMS and decrease in MF during isometric
      contractions, and reduction in MVC force immediately after the exercise was
      greater (p < 0.05) for low-intensity fatigue task. We conclude that low-intensity
      isometric contractions, repeatedly sustained to fatigue, resulted in a marked
      increase in the EMG amplitude and spectral compression without a significant post
      fatigue reflex inhibition of soleus motoneuron pool. High-intensity contractions,
      however, resulted in post-fatigue reflex inhibition of soleus motoneuron pool and
      less pronounced EMG spectral compression during fatiguing contractions. A failure
      of neuromuscular transmission-propagation was not evident after repetitive
      fatiguing isometric contractions.

PMID- 18051629
TI  - The relationship between skin temperature and neuronal characteristics in the
      median, ulnar and radial nerves of non-impaired individuals.
AB  - The purpose of this study was to evaluate the relationship between the nerve
      conduction characteristics in the median, ulnar and radial nerves and presenting
      skin temperature in non-impaired individuals as they were subjected to
      electrophysiological testing. Previous researchers artificially manipulated the
      skin temperature and demonstrated that there was a positive relationship between
      temperature and nerve conduction velocity and a negative correlation between
      distal latency and evoked motor action potential (EMAP). The sample population
      was 50 non-impaired individuals derived from a venue in the New York City and
      Long Island region. The independent variable was skin temperature. The dependent
      variables were: motor nerve conduction velocity, motor distal latency, EMAP of
      median and ulnar nerves, sensory distal latency and sensory nerve action
      potential (SNAP) of median, ulnar and radial nerves. The data were analyzed using
      descriptive statistics, the Bonferroni correction factor and correlation
      statistics. The study showed significant correlation in median motor distal
      latency, ulnar motor distal latency, ulnar sensory distal latency, median sensory
      amplitude, and ulnar sensory amplitude. The NCV, the distal latency and the
      amplitude of the median, ulnar and radial nerves were similar in values to other
      researchers' normal values.

PMID- 18051630
TI  - Neurophysiological monitoring of lumbosacral spinal roots during spinal surgery:
      continuous intraoperative electromyography (EMG).
AB  - INTRODUCTION: Neurophysiological monitoring during spinal surgery reduces the
      associated neurological complications. Continuous EMG recording has developed an
      useful technique for spinal root monitoring PATIENTS AND METHODS: Fifty four
      patients who underwent surgery for several lumbosacral spinal lesions (low and
      high degree spondylolisthesis, spinal stenosis, degenerated or herniated lumbar
      discs) were studied to evaluate the effectiveness of continuous EMG recording in
      monitoring spinal root function during surgery. Electrical root or screw
      stimulation was also performed in nine of them. To correlate surgical spinal root
      lesion with a precise EMG injury activity an animal study with 5 pigs was
      performed; lesion was produced by prolonged spinal root traction. RESULTS: In the
      porcine group EMG discharges lasting longer than one minute after cessation of
      root traction was noted in 74% of spinal root levels (neurotonic discharges or
      pseudo-rhythmic activity in 70% of the cases). Spinal root lesion was
      demonstrated through EMG three weeks after surgery. In the patient group
      pathological-significant EMG activity was not recorded in any case during
      monitoring. Mechanical or chemical root stimulation during surgery produced brief
      lasting EMG bursts of no pathological significance. Only a patient developed a
      mild acute L5-S1 radiculopathy after surgery (1 false negative) and post
      operative deficit was not observed in the rest. Electrical stimulation of spinal
      roots and screws allowed to identify root level and prove the adequate placement
      of screws. CONCLUSION: Spontaneous and evoked EMG recordings are simple
      techniques that provide continuous information about lumbosacral spinal roots
      function throughout surgery.

PMID- 18051631
TI  - Introduction of the vastus medialis oblique H-reflex during traction of the leg.
AB  - To clarify the excitability of the alpha-motoneuron pool corresponding to the
      vastus medialis oblique (VMO), this study investigated the H-reflex from the VMO
      by traction of the leg. One healthy male subject participated in this study, and
      retesting was performed after 3 days. The surface stimulating electrodes were
      applied over the course of the femoral nerve on the skin immediately distal to
      the inguinal ligament. An active electrode for recording the H-reflex was placed
      on the VMO, and a reference electrode was placed immediately proximal to the
      patella. The H-reflex was recorded before, during and after traction of the leg.
      Two patterns of H-reflex modulations were found as follows: 1) the H-reflex
      amplitudes tended to be lower during traction than before traction, 2) the H
      reflex amplitudes tended to be higher after traction. With regard to the decrease
      in H-reflex amplitude during traction of the leg, the Ib inhibition for the VMO
      was believed to have occurred by prolonged stretching of the quadriceps tendon
      and patellar tendon. Also, with regard to the tendency of the VMO H-reflex to
      increase after traction, disinhibition of the alpha-motoneuron might have
      occurred in this study.

PMID- 18051632
TI  - Changes in ulnar nerve conduction velocity across the elbow in different angles
      of elbow flexion.
AB  - OBJECTIVES: The goal of this study is to determine the changes in motor and
      sensory nerve conduction velocity (NCV) of ulnar nerve at elbow area in different
      angles of elbow flexion and also to define the optimum angle at which there is an
      ideal correlation between the across elbow and below elbow NCVs of ulnar nerve.
      METHODS: Motor and sensory NCVs of ulnar nerve were studied in 50 able-bodied
      subjects (100 limbs) for the below elbow and across elbow segments to evaluate
      the effect of 5 different angles of elbow (0 degrees, 45 degrees, 90 degrees, 110
      degrees 135 degrees of elbow flexion) on NCV changes of ulnar nerve. At each
      angle the across elbow NCVs were measured and compared with below elbow segments.
      RESULTS: At 0 degrees of elbow flexion the across elbow NCVs were found to be
      slower than below elbow segments and at 45 degrees there was no statistical
      difference between below elbow and across elbow NCV. At each subsequent angles of
      elbow flexion there was an increment in motor and sensory NCVs for the across
      elbow compared to below elbow segment (P < 0.05). This increment progressed as
      the degree of flexion increased, so the most erroneous increment was found at 135
      degrees of elbow flexion. CONCLUSIONS: Since the 45 degrees of elbow flexion was
      found to be the position of least variation in motor and sensory NCVs between the
      across elbow and below elbow segments, this position of elbow flexion seems to be
      the ideal angle during nerve conduction study of ulnar nerve at elbow area. In
      this position the upper limit of normal difference between across elbow and below
      elbow motor NCVs (mean + 2SD) was calculated 8 m/sec.

PMID- 18051633
TI  - Lumbosarcral radiculopathties--the importance of EDX information other than
      needle electromyography.
AB  - OBJECTIVE: This study evaluates the importance of varying electrodiagnostic (EDX)
      parameters abnormalities in patients with possible lumbosacral radiculopathies
      (LSR). METHODS: 34 patients referred for EDX studies with clinical findings
      consistent with a LSR without other causes for their symptoms were evaluated.
      Studies included not only standard (Routine EDX) nerve conduction studies (NCS)
      including F-waves and needle electromyography (nEMG) but also a multiparameter
      automated analysis system using prefabricated nerve conduction electrodes without
      nEMG (NC-stat EDX). RESULTS: Abnormal Routine EDX was present in 24 of the
      patients. Abnormal nEMG was present in only 14 of these patients, all of whom
      also had other relevant NCS abnormalities. Abnormal NC-stat EDX was found in 29
      of the patients. In all but one patient there was agreement in the radicular
      localization between Routine and NC-stat EDX. In 30 patients, there was recent
      computed tomography or magnetic resonance imaging of the lumbosacral region.
      Comparable statistical agreements with the radiographic information were obtained
      for Routine EDX and NC-stat data. This was true including when the analyses were
      based on the neuroradiological evaluation of likely root injury. CONCLUSION: This
      study emphasizes the importance of EDX studies other than nEMG in the evaluation
      of patients with possible LSR and supports the value of a computerized
      mutliparameter methodology in these patients.

PMID- 18051634
TI  - Predators, parasitoids, and pathogens: a cross-cutting examination of intraguild
      predation theory.
AB  - Although the canonical concept of intraguild predation evokes images of predators
      and prey, several subdisciplines within ecology have developed theory not
      specifically framed in terms of predation and competition and often using system
      specific terminology, yet functionally quite similar. Here, we formulate models
      combining exploitation and competition in predator-prey, host-parasitoid, and
      host-pathogen communities to compare dynamics, food web structure, and
      coexistence criteria for these disparate communities. Although dynamic stability
      in the coexistence region varies strongly among systems, in all cases coexistence
      of two consumers on a single resource occurs only if the intraguild prey species
      is more efficient than the intraguild predator at suppressing the abundance of
      the basal resource, and if the intraguild predator accrues a sufficient gain from
      attacking the intraguild prey. In addition, equilibrial abundances of all species
      in all three formulations respond similarly to increases in productivity of the
      basal resource. Our understanding of predator-prey and parasitoid-host
      communities has benefited from explicit examination of intraguild predation (IGP)
      theory, and we suggest that future research examining pathogen communities, in
      particular, will benefit substantially from explicit recognition of predictions
      from IGP theory.

PMID- 18051635
TI  - The influence of intraguild predation on prey suppression and prey release: a
      meta-analysis.
AB  - Intraguild predation (IGP) occurs when one predator species consumes another
      predator species with whom it also competes for shared prey. One question of
      interest to ecologists is whether multiple predator species suppress prey
      populations more than a single predator species, and whether this result varies
      with the presence of IGP. We conducted a meta-analysis to examine this question,
      and others, regarding the effects of IGP on prey suppression. When predators can
      potentially consume one another (mutual IGP), prey suppression is greater in the
      presence of one predator species than in the presence of multiple predator
      species; however, this result was not found for assemblages with unidirectional
      or no IGP. With unidirectional IGP, intermediate predators were generally more
      effective than the top predator at suppressing the shared prey, in agreement with
      IGP theory. Adding a top predator to an assemblage generally caused prey to be
      released from predation, while adding an intermediate predator caused prey
      populations to be suppressed. However, the effects of adding a top or
      intermediate predator depended on the effectiveness of these predators when they
      were alone. Effects of IGP varied across different ecosystems (e.g., lentic,
      lotic, marine, terrestrial invertebrate, and terrestrial vertebrate), with the
      strongest patterns being driven by terrestrial invertebrates. Finally, although
      IGP theory is based on equilibrium conditions, data from short-term experiments
      can inform us about systems that are dominated by transient dynamics. Moreover,
      short-term experiments may be connected in some way to equilibrium models if the
      predator and prey densities used in experiments approximate the equilibrium
      densities in nature.

PMID- 18051636
TI  - The interaction of cannibalism and omnivory: consequences for community dynamics.
AB  - Although cannibalism is ubiquitous in food webs and frequent in systems where a
      predator and its prey also share a common resource (intraguild predation, IGP),
      its impacts on species interactions and the dynamics and structure of communities
      are still poorly understood. In addition, the few existing studies on cannibalism
      have generally focused on cannibalism in the top-predator, ignoring that it is
      frequent at intermediate trophic levels. A set of structured models shows that
      cannibalism can completely alter the dynamics and structure of three-species IGP
      systems depending on the trophic position where cannibalism occurs. Contrary to
      the expectations of simple models, the IG predator can exploit the resources more
      efficiently when it is cannibalistic, enabling the predator to persist at lower
      resource densities than the IG prey. Cannibalism in the IG predator can also
      alter the effect of enrichment, preventing predator-mediated extinction of the IG
      prey at high productivities predicted by simple models. Cannibalism in the IG
      prey can reverse the effect of top-down cascades, leading to an increase in the
      resource with decreasing IG predator density. These predictions are consistent
      with current data. Overall, cannibalism promotes the coexistence of the IG
      predator and IG prey. These results indicate that including cannibalism in
      current models can overcome the discrepancy between theory and empirical data.
      Thus, we need to measure and account for cannibalistic interactions to reliably
      predict the structure and dynamics of communities.

PMID- 18051637
TI  - Alternative prey and the dynamics of intraguild predation: theoretical
      perspectives.
AB  - A rich body of theoretical literature now exists focused on the three-species
      module of intraguild predation (IGP), in which a top predator both attacks and
      competes with an intermediate predator. Simple models of intraguild predation are
      often unstable, either because one consumer is excluded, or because sustained
      oscillations emerge from long feedback loops. Yet, many natural IGP systems
      robustly persist. Standard models of intraguild predation simplify natural
      systems in crucial ways that could influence persistence; in particular, many
      empirical IGP systems are embedded in communities with alternative prey species.
      We briefly review the key conclusions of standard three-species IGP theory, and
      then present results of theoretical explorations of how alternative prey can
      influence the persistence and stability of a focal intraguild predation
      interaction.

PMID- 18051638
TI  - Habitat structure affects intraguild predation.
AB  - Intraguild predation is thought to be ubiquitous in natural food webs. Yet,
      theory on intraguild predation predicts the intraguild prey to persist only under
      limited conditions. This gap between theory and empirical observations needs
      scrutiny. One reason might be that theory has focused on equilibrium dynamics and
      a limited set of species (usually three) that interact in well-mixed populations
      in unstructured habitats, and these assumptions will often not hold in natural
      systems. In this review, we focus on the effects of habitat structure on
      intraguild predation. Habitat structure could reduce encounter rates between
      predators and prey and could create refuges for prey. In both cases, habitat
      structure could reduce the strength of intraguild interactions, thereby
      facilitating species coexistence. A meta-analysis of studies on manipulation of
      habitat structure shows that intraguild prey indeed suffer less from intraguild
      predation in structured habitats. This was further confirmed by a meta-analysis
      in which studies on intraguild predation were classified according to habitat
      structure. Intraguild predation reduced densities of the intraguild prey
      significantly more in habitats with little structure than in habitats rich in
      structure. The effect of intraguild predation on the shared prey was negative,
      and not significantly affected by habitat structure. We conclude that habitat
      structure may increase persistence of the intraguild prey by decreasing the
      strength of the interaction between intraguild predator and intraguild prey.

PMID- 18051639
TI  - Trade-offs, temporal variation, and species coexistence in communities with
      intraguild predation.
AB  - Intraguild predation/parasitism (IGP: competing species preying on or
      parasitizing each other) is widespread in nature, but the mechanisms by which
      intraguild prey and predators coexist remain elusive. Theory predicts that a
      trade-off between resource competition and IGP should allow local niche
      partitioning, but such trade-offs are expressed only at intermediate resource
      productivity and cannot explain observations of stable coexistence at high
      productivity. Coexistence must therefore involve additional mechanisms beside the
      trade-off, but very little is known about the operation of such mechanisms in
      nature. Here I present the first experimental test of multiple coexistence
      mechanisms in a natural community exhibiting IGP. The results suggest that, when
      resource productivity constrains the competition-IGP trade-off, a temporal refuge
      for the intraguild prey can not only promote coexistence, but also change species
      abundances to a pattern qualitatively different from that expected based on the
      trade-off or a refuge alone. This is the first empirical study to demonstrate a
      mechanism for why communities with IGP do not lose species diversity in highly
      productive environments. These results have implications for diversity
      maintenance in multi-trophic communities, and the use of multiple natural enemies
      in biological control.

PMID- 18051640
TI  - Pre-migratory life history stages of juvenile Arctic birds: costs, constraints,
      and trade-offs.
AB  - Many young birds on the Arctic tundra are confronted by a challenging task: they
      must molt their feathers and accumulate fat stores for the autumn migration
      before climatic conditions deteriorate. Our understanding of the costs and
      constraints associated with these stages is extremely limited. We investigated
      post-juvenal molt and premigratory fattening in free-ranging juvenile White
      crowned Sparrows (Zonotrichia leucophrys gambelii) on the Arctic tundra. We found
      evidence for trade-offs between premigratory fat accumulation and molt: heavily
      molting birds had significantly less fat. Birds increased the rate of fat
      accumulation as the season progressed, but we found no evidence of a similar
      increase in rate of molt. Using a controlled captive study to isolate the
      energetic costs of body feather replacement, we found no difference in fat or
      size-corrected mass of birds actively growing body feathers as compared to
      controls. Molting birds, however, consumed 17% more food than controls,
      suggesting a significant cost of body feather growth. Our results provide
      evidence of significant costs, constraints, and trade-offs associated with post
      juvenal molt and premigratory fat accumulation in young Arctic birds.

PMID- 18051641
TI  - Geographical gradients in diet affect population dynamics of Canada lynx.
AB  - Geographical gradients in the stability of cyclic populations of herbivores and
      their predators may relate to the degree of specialization of predators. However,
      such changes are usually associated with transition from specialist to generalist
      predator species, rather than from geographical variation in dietary breadth of
      specialist predators. Canada lynx (Lynx canadensis) and snowshoe hare (Lepus
      americanus) populations undergo cyclic fluctuations in northern parts of their
      range, but cycles are either greatly attenuated or lost altogether in the
      southern boreal forest where prey diversity is higher. We tested the influence of
      prey specialization on population cycles by measuring the stable carbon and
      nitrogen isotope ratios in lynx and their prey, estimating the contribution of
      hares to lynx diet across their range, and correlating this degree of
      specialization to the strength of their population cycles. Hares dominated the
      lynx diet across their range, but specialization on hares decreased in southern
      and western populations. The degree of specialization correlated with cyclic
      signal strength indicated by spectral analysis of lynx harvest data, but overall
      variability of lynx harvest (the standard deviation of natural-log-transformed
      harvest numbers) did not change significantly with dietary specialization. Thus,
      as alternative prey became more important in the lynx diet, the fluctuations
      became decoupled from a regular cycle but did not become less variable. Our
      results support the hypothesis that alternative prey decrease population cycle
      regularity but emphasize that such changes may be driven by dietary shifts among
      dominant specialist predators rather than exclusively through changes in the
      predator community.

PMID- 18051642
TI  - Predator hunting mode and habitat domain alter nonconsumptive effects in predator
      prey interactions.
AB  - Predators can affect prey populations through changes in traits that reduce
      predation risk. These trait changes (nonconsumptive effects, NCEs) can be
      energetically costly and cause reduced prey activity, growth, fecundity, and
      survival. The strength of nonconsumptive effects may vary with two functional
      characteristics of predators: hunting mode (actively hunting, sit-and-pursue, sit
      and-wait) and habitat domain (the ability to pursue prey via relocation in space;
      can be narrow or broad). Specifically, cues from fairly stationary sit-and-wait
      and sit-and-pursue predators should be more indicative of imminent predation
      risk, and thereby evoke stronger NCEs, compared to cues from widely ranging
      actively hunting predators. Using a meta-analysis of 193 published papers, we
      found that cues from sit-and-pursue predators evoked stronger NCEs than cues from
      actively hunting predators. Predator habitat domain was less indicative of NCE
      strength, perhaps because habitat domain provides less reliable information
      regarding imminent risk to prey than does predator hunting mode. Given the
      importance of NCEs in determining the dynamics of prey communities, our findings
      suggest that predator characteristics may be used to predict how changing
      predator communities translate into changes in prey. Such knowledge may prove
      particularly useful given rates of local predator change due to habitat
      fragmentation and the introduction of novel predators.

PMID- 18051643
TI  - Herbivory mediates grass-endophyte relationships.
AB  - Endophytic fungi are plant symbionts living asymptomatically within plant
      tissues. Neotyphodium spp., which are asexual vertically transmitted systemic
      fungal endophytes of cool-season grasses, are predicted to be plant mutualists.
      These endophytes increase host plant resistance to environmental stresses and/or
      increase the production of alkaloid-based herbivore deterrents. The ubiquity of
      this defense mutualism is unclear, and a variety of alternative mechanisms may
      explain the observed variation in infection rates, levels of deterrence, and the
      maintenance of asexual endophytes in grass populations. We found that grass
      endophyte interactions are variable and ordered along an herbivory gradient in an
      undisturbed subarctic alpine ecosystem. Native grass populations in grazed sites
      had significantly greater frequency of Neotyphodium infection compared to
      ungrazed sites. Tillers from grazed sites had significantly higher hyphal
      densities compared to ungrazed sites. The ability of grass-Neotyphodium
      constituents to deter vertebrate herbivory in natural systems is thought to be
      rare. In grazed meadows, we showed that endophyte infection resulted in the
      deterrence of grazing by native vertebrate herbivores. However, the same
      herbivores did not distinguish between infected and uninfected grass harvested
      from ungrazed areas. These results demonstrate that the relationship between
      vertically transmitted endophytes and grasses in the alpine tundra vary greatly
      within populations. This may be based in part on defense mutualism and is
      consistent, under varying levels of herbivory, with the predictions of optimal
      defense theory.

PMID- 18051644
TI  - Increased plant size in exotic populations: a common-garden test with 14 invasive
      species.
AB  - The "evolution of increased competitive ability" (EICA) hypothesis predicts that
      exotic species will adapt to reduced herbivore pressure by losing costly defenses
      in favor of competitive ability. Previous studies often support the prediction
      that plants from exotic populations will be less well defended than plants from
      native populations. However, results are mixed with respect to the question of
      whether plants from exotic populations have become more competitive. In a common
      garden experiment involving plants from two native and two exotic populations of
      14 different invasive species, we tested whether exotic plants generally grow
      larger than conspecific native plants, and whether patterns of relative growth
      depend on the intensity of competition. We found a quite consistent pattern of
      larger exotic than native plants, but only in the absence of competition. These
      results suggest that invasive species may often evolve increased growth, and that
      increased growth may facilitate adaptation to noncompetitive environments.

PMID- 18051645
TI  - Quasi-Poisson vs. negative binomial regression: how should we model overdispersed
      count data?
AB  - Quasi-Poisson and negative binomial regression models have equal numbers of
      parameters, and either could be used for overdispersed count data. While they
      often give similar results, there can be striking differences in estimating the
      effects of covariates. We explain when and why such differences occur. The
      variance of a quasi-Poisson model is a linear function of the mean while the
      variance of a negative binomial model is a quadratic function of the mean. These
      variance relationships affect the weights in the iteratively weighted least
      squares algorithm of fitting models to data. Because the variance is a function
      of the mean, large and small counts get weighted differently in quasi-Poisson and
      negative binomial regression. We provide an example using harbor seal counts from
      aerial surveys. These counts are affected by date, time of day, and time relative
      to low tide. We present results on a data set that showed a dramatic difference
      on estimating abundance of harbor seals when using quasi-Poisson vs. negative
      binomial regression. This difference is described and explained in light of the
      different weighting used in each regression method. A general understanding of
      weighting can help ecologists choose between these two methods.

PMID- 18051646
TI  - On the choice of statistical models for estimating occurrence and extinction from
      animal surveys.
AB  - In surveys of natural animal populations the number of animals that are present
      and available to be detected at a sample location is often low, resulting in few
      or no detections. Low detection frequencies are especially common in surveys of
      imperiled species; however, the choice of sampling method and protocol also may
      influence the size of the population that is vulnerable to detection. In these
      circumstances, probabilities of animal occurrence and extinction will generally
      be estimated more accurately if the models used in data analysis account for
      differences in abundance among sample locations and for the dependence between
      site-specific abundance and detection. Simulation experiments are used to
      illustrate conditions wherein these types of models can be expected to outperform
      alternative estimators of population site occupancy and extinction.

PMID- 18051647
TI  - Random forests for classification in ecology.
AB  - Classification procedures are some of the most widely used statistical methods in
      ecology. Random forests (RF) is a new and powerful statistical classifier that is
      well established in other disciplines but is relatively unknown in ecology.
      Advantages of RF compared to other statistical classifiers include (1) very high
      classification accuracy; (2) a novel method of determining variable importance;
      (3) ability to model complex interactions among predictor variables; (4)
      flexibility to perform several types of statistical data analysis, including
      regression, classification, survival analysis, and unsupervised learning; and (5)
      an algorithm for imputing missing values. We compared the accuracies of RF and
      four other commonly used statistical classifiers using data on invasive plant
      species presence in Lava Beds National Monument, California, USA, rare lichen
      species presence in the Pacific Northwest, USA, and nest sites for cavity nesting
      birds in the Uinta Mountains, Utah, USA. We observed high classification accuracy
      in all applications as measured by cross-validation and, in the case of the
      lichen data, by independent test data, when comparing RF to other common
      classification methods. We also observed that the variables that RF identified as
      most important for classifying invasive plant species coincided with expectations
      based on the literature.

PMID- 18051649
TI  - Habitat provisioning for aboveground predators decreases detritivores.
AB  - Although provisioning of habitat by ecosystem engineers is one of the most common
      biological interactions, previous studies have mostly focused on facilitative or
      bottom-up processes. Here we show that engineering effects can indirectly
      strengthen top-down effects mediated by predator abundance. We conducted a small
      scale manipulative field experiment and broad-scale field observations of the
      plant, web spider, and detrital insect system in forest understory habitats. In
      the field experiment, artificially increasing architectural elements enhanced the
      abundance of spiders by providing physical support for web building. Moreover,
      aerial insects derived from the detrital food web decreased in response to
      increased spider abundance. As artificial architecture per se did not affect
      aerial detritivores, these results indicate that ecosystem engineering indirectly
      strengthens top-down effects mediated by predators. In field observations
      conducted in 12 cedar forests, path analyses supported the importance of an
      indirect pathway originating from understory vegetation complexity to spider
      abundance and to aerial detritivores. The effect size of spiders on detrital
      insects was similar in the field experiment and in the observations. These
      results indicate that the engineering effects of plants cascade to detrital
      insects through web spiders across different scales.

PMID- 18051648
TI  - Quantitative approaches to the analysis of stable isotope food web data.
AB  - Ecologists use stable isotopes (delta13C, delta15N) to better understand food
      webs and explore trophic interactions in ecosystems. Traditionally, delta13C vs.
      delta15N bi-plots have been used to describe food web structure for a single time
      period or ecosystem. Comparisons of food webs across time and space are
      increasing, but development of statistical approaches for testing hypotheses
      regarding food web change has lagged behind. Here we present statistical
      methodologies for quantitatively comparing stable isotope food web data. We
      demonstrate the utility of circular statistics and hypothesis tests for
      quantifying directional food web differences using two case studies: an arthropod
      salt marsh community across a habitat gradient and a freshwater fish community
      from Lake Tahoe, USA, over a 120-year time period. We calculated magnitude and
      mean angle of change (theta) for each species in food web space using mean
      delta13C and delta15N of each species as the x, y coordinates. In the coastal
      salt marsh, arthropod consumers exhibited a significant shift toward dependence
      on Spartina, progressing from a habitat invaded by Phragmites to a restored
      Spartina habitat. In Lake Tahoe, we found that all species from the freshwater
      fish community shifted in the same direction in food web space toward more
      pelagic-based production with the introduction of nonnative Mysis relicta and
      onset of cultural eutrophication. Using circular statistics to quantitatively
      analyze stable isotope food web data, we were able to gain significant insight
      into patterns and changes in food web structure that were not evident from
      qualitative comparisons. As more ecologists incorporate a food web perspective
      into ecosystem analysis, these statistical tools can provide a basis for
      quantifying directional food web differences from standard isotope data.

PMID- 18051650
TI  - Trophic structure of coastal Antarctic food webs associated with changes in sea
      ice and food supply.
AB  - Predicting the dynamics of ecosystems requires an understanding of how trophic
      interactions respond to environmental change. In Antarctic marine ecosystems,
      food web dynamics are inextricably linked to sea ice conditions that affect the
      nature and magnitude of primary food sources available to higher trophic levels.
      Recent attention on the changing sea ice conditions in polar seas highlights the
      need to better understand how marine food webs respond to changes in such broad
      scale environmental drivers. This study investigated the importance of sea ice
      and advected primary food sources to the structure of benthic food webs in
      coastal Antarctica. We compared the isotopic composition of several seafloor taxa
      (including primary producers and invertebrates with a variety of feeding modes)
      that are widely distributed in the Antarctic. We assessed shifts in the trophic
      role of numerically dominant benthic omnivores at five coastal Ross Sea
      locations. These locations vary in primary productivity and food availability,
      due to their different levels of sea ice cover, and proximity to polynyas and
      advected primary production. The delta15N signatures and isotope mixing model
      results for the bivalves Laternula elliptica and Adamussium colbecki and the
      urchin Sterechinus neumeyeri indicate a shift from consumption of a higher
      proportion of detritus at locations with more permanent sea ice in the south to
      more freshly produced algal material associated with proximity to ice-free water
      in the north and east. The detrital pathways utilized by many benthic species may
      act to dampen the impacts of large seasonal fluctuations in the availability of
      primary production. The limiting relationship between sea ice distribution and in
      situ primary productivity emphasizes the role of connectivity and spatial
      subsidies of organic matter in fueling the food web. Our results begin to provide
      a basis for predicting how benthic ecosystems will respond to changes in sea ice
      persistence and extent along environmental gradients in the high Antarctic.

PMID- 18051651
TI  - Biodiversity mediates productivity through different mechanisms at adjacent
      trophic levels.
AB  - Biodiversity may enhance productivity either because diverse communities more
      often contain productive species (selection effects) or because they show greater
      complementarity in resource use. Our understanding of how these effects influence
      community production comes almost entirely from studies of plants. To test
      whether previous results apply to higher trophic levels, we first used
      simulations to derive expected contributions of selection and complementarity to
      production in competitive assemblages defined by either neutral interactions,
      dominance, or a trade-off between growth and competitive ability. The three types
      of simulated assemblages exhibited distinct interaction signatures when diversity
      effects were partitioned into selection and complementarity components. We then
      compared these signatures to those of experimental marine communities. Diversity
      influenced production in fundamentally different ways in assemblages of
      macroalgae, characterized by growth-competition trade-offs, vs. in herbivores,
      characterized by dominance. Forecasting the effects of changing biodiversity in
      multitrophic ecosystems will require recognizing that the mechanism by which
      diversity influences functioning can vary among trophic levels in the same food
      web.

PMID- 18051652
TI  - A multivariate analysis of beta diversity across organisms and environments.
AB  - We examined variability in hierarchical beta diversity across ecosystems,
      geographical gradients, and organism groups using multivariate spatial mixed
      modeling analysis of two independent data sets. The larger data set comprised
      reported ratios of regional species richness (RSR) to local species richness
      (LSR) and the second data set consisted of RSR:LSR ratios derived from nested
      species-area relationships. There was a negative, albeit relatively weak,
      relationship between beta diversity and latitude. We found only relatively subtle
      differences in beta diversity among the realms, yet beta diversity was lower in
      marine systems than in terrestrial or freshwater realms. Beta diversity varied
      significantly among organisms' major characteristics such as body mass, trophic
      position, and dispersal type in the larger data set. Organisms that disperse via
      seeds had highest beta diversity, and passively dispersed organisms showed the
      lowest beta diversity. Furthermore, autotrophs had lower beta diversity than
      organisms higher up the food web; omnivores and carnivores had consistently
      higher beta diversity. This is evidence that beta diversity is simultaneously
      controlled by extrinsic factors related to geography and environment, and by
      intrinsic factors related to organism characteristics.

PMID- 18051653
TI  - Modification of hosts' behavior by a parasite: field evidence for adaptive
      manipulation.
AB  - Parasites relying on trophic transmission to complete their life cycles often
      induce modifications of their host's behavior in ways that may increase their
      susceptibility to predation by final hosts. These modifications have often been
      interpreted as parasite adaptations, but very few studies have demonstrated that
      host manipulation has fitness benefits for the parasite. The aim of the present
      study was to address the adaptive significance of parasite manipulation by
      coupling observations of behavioral manipulation to estimates of trophic
      transmission to the definitive host in the natural environment. We show that the
      acanthocephalan parasite Pomphorhynchus laevis manipulates the drifting behavior
      of one of its intermediate hosts, the amphipod Gammarus pulex, but not of a
      sympatric host, the introduced amphipod Gammarus roeseli. We found a 26.3-28.3
      times higher proportion of infected G. pulex in the stomach content of one of the
      definitive hosts of P. laevis, the bullhead Cottus gobio, than in the benthos. No
      such trend was observed for G. roeseli. The bell-shaped curve of mean parasite
      abundance (MPA) relative to host size observed in G. pulex also supported an
      increased predation mortality of P. laevis-infected individuals compared to
      uninfected amphipods. Again, no such pattern was observed in G. roeseli.
      Furthermore, our results indicate that the modifications induced by P. laevis are
      specific to the definitive host and do not increase the risk of predation by
      inappropriate hosts, here the adult edible frog Rana esculenta. Overall, our
      study is original in that it establishes, under field conditions, a direct link
      between parasitic manipulation and increased transmission to the definitive host,
      and more importantly, identifies the specificity of the manipulation both in the
      intermediate host species and toward the definitive host.

PMID- 18051654
TI  - The inflationary effects of environmental fluctuations ensure the persistence of
      sink metapopulations.
AB  - Under current rates of environmental change many populations may be found in
      habitats of low quality and low conservation value, creating population sinks. We
      test recent theory that suggests, surprisingly, that stochastic environmental
      variability may enhance the long-term persistence of sink metapopulations. Using
      experimental populations of Paramecium aurelia we show that it is possible for a
      metapopulation comprised entirely of sink populations to persist for many
      generations in a random environment. In accordance with the theory, we show that
      positive temporal autocorrelation and low spatial correlation in the environment
      can ensure the long-term persistence and enhance the mean and maximum abundance
      of sink metapopulations. High levels of spatial correlation in the environment
      created strong population synchrony and limited the persistence time of the sink
      metapopulations. These results have important implications for the development of
      a theory underlying the synergistic effects of habitat fragmentation and
      environmental change on population persistence.

PMID- 18051655
TI  - Population inertia and its sensitivity to changes in vital rates and population
      structure.
AB  - Because the (st)age structure of a population may rarely be stable, studies of
      transient population dynamics and population momentum are becoming ever more
      popular. Yet, studies of "population momentum" are restricted in the sense that
      they describe the inertia of population size resulting from a demographic
      transition to the stationary population growth rate. Although rarely mentioned,
      inertia in population size is a general phenomenon and can be produced by any
      demographic transition or perturbation. Because population size is of central
      importance in demography, conservation, and management, formulas relating the
      sensitivity of population inertia to changes in underlying vital rates and
      population structure could provide much-needed insight into the dynamics of
      populations with unstable (st)age structure. Here, we derive such formulas, which
      are readily computable, and provide examples of their potential use in studies of
      life history and applied arenas of population study.

PMID- 18051656
TI  - Host plant quality and local adaptation determine the distribution of a gall
      forming herbivore.
AB  - Herein we report results of transplant experiments that link variation in host
      plant quality to herbivore fitness at the local scale (among adjacent plants)
      with the process of local (demic) adaptation at the landscape scale to explain
      the observed distribution of the specialist gall former Belonocnema treatae
      (Hymenoptera: Cynipidae) within populations of its host plant, Quercus
      fusiformis. Field surveys show that leaf gall densities vary by orders of
      magnitude among adjacent trees and that high-gall-density trees are both rare (<
      5%) and patchily distributed. B. treatae from each of five high-gall-density
      trees were reared on (1) the four nearest low-gall-density trees, (2) the four
      alternative high-gall-density trees, and (3) their natal trees (control). Each
      treatment (source X rearing site) was replicated three times. Nine components of
      performance that sequentially contribute to fitness were evaluated with over
      21000 galls censused across the 25 experimental trees. When reared on their natal
      trees and compared with low-gall-density neighbors, transplanted gall formers had
      higher gall initiation success (P < 0.05), produced more (P < 0.001) and larger
      galls (P < 0.001), and produced a higher proportion of galls that exceeded the
      threshold size for natural enemy avoidance (P < 0.05). Comparison of gall-former
      performance on natal vs. alternative high-gall-density trees demonstrated
      significant (P < 0.001) differences in six performance measures with five
      differing in the direction predicted by the hypothesis of local adaptation.
      Overall, these linked experiments document direct and indirect effects of host
      plant variation on gall-former performance and demonstrate convincingly that (1)
      high-gall-density trees equate to high-quality trees that are surrounded by trees
      of relatively lower quality to the herbivore and (2) gall-former populations have
      become locally adapted to individual trees.

PMID- 18051657
TI  - Variation in responses of late-seral herbs to disturbance and environmental
      stress.
AB  - Clonal herbs that attain maximum development in late-seral forest are often
      assumed to have similar responses to disturbance and to be functionally
      equivalent. However, little is known about the demographic or physiological
      responses of these plants to disturbance or to the altered conditions of the post
      disturbance environment. Following harvest of a mature coniferous forest, we
      compared abundance, demographic changes, and physiological acclimation of three
      clonal herbs (Asarum caudatum, Clintonia uniflora, and Pyrola picta) that differ
      in belowground morphology and leaf longevity. We measured ramet density, leaf
      area, and demographic variables (survival, clonal growth, flowering, and seedling
      establishment) before and for two years after harvest, and in adjacent
      undisturbed forest. Acclimation to increased solar radiation was assessed two
      years after harvest by measuring leaf mass per unit area (LMA) and chlorophyll
      a:b ratios of leaves produced in the current year. Although initial declines in
      abundance were similar, demographic responses indicate that patterns of recovery
      varied greatly among species. Two years after logging, ramet survival and clonal
      growth (production of new ramets) of Clintonia were greater in the harvest area
      than in the forest. Asarum had lower survival in the harvest area, but greater
      clonal growth, and Pyrola showed no difference in either survival or growth
      between environments. Only Asarum produced seedlings, although their survival was
      low in the harvest area. All species had higher LMA in the harvest area, but only
      Clintonia (with annual leaves) had a higher chlorophyll a:b ratio, suggesting the
      greatest potential for acclimation to increased light. Our results demonstrate
      that forest herbs with greater rhizome plasticity and shorter leaf duration have
      greater potential to acclimate after disturbance than those with rigid
      architectures and persistent leaves. Thus, species with comparable successional
      roles can vary substantially in their demographic and physiological responses to
      disturbance, with potential consequences for long-term recovery.

PMID- 18051658
TI  - Multidecadal climate variability and climate interactions affect subalpine fire
      occurrence, western Colorado (USA).
AB  - This study investigates the influence of climatic variability on subalpine forest
      fire occurrence in western Colorado during the AD 1600-2003 period. Interannual
      and multidecadal relationships between fire occurrence and the El Nino Southern
      Oscillation (ENSO), Pacific Decadal Oscillation (PDO), and Atlantic Multidecadal
      Oscillation (AMO) were examined, in addition to the effects of phase interactions
      among these oscillations. Fires occurred during short-term periods of significant
      drought and extreme cool (negative) phases of ENSO and PDO and during positive
      departures from mean AMO index. At longer time scales, fires exhibited 20-year
      periods of synchrony with the cool phase of the PDO, and 80-year periods of
      synchrony with extreme warm (positive) phases of the AMO. Years of combined
      positive AMO and negative ENSO and PDO phases represent "triple whammies" that
      significantly increased the occurrence of drought-induced fires. Fires were
      synchronous with this phase combination over 0-30 year periods and distinctly
      asynchronous with the opposite phase combination. Overall, because fires are
      synchronous at supra-annual to multidecadal time scales with warm AMO events,
      particularly when combined with cool ENSO and PDO phases, this suggests that we
      may be entering a qualitatively different fire regime in the next few decades due
      to the recent shift in 1998 to a likely long-term warm AMO phase. Although
      uncertainty remains regarding the effects of CO2-induced warming at regional
      scales, given the multidecadal persistence of the AMO there is mounting evidence
      that the recent shift to the positive phase of the AMO will promote higher fire
      frequencies in the region.

PMID- 18051659
TI  - Effects of macrophyte functional group richness on emergent freshwater wetland
      functions.
AB  - Most plant diversity-function studies have been conducted in terrestrial
      ecosystems and have focused on plant productivity and nutrient uptake/retention,
      with a notable lack of attention paid to belowground processes (e.g., root
      dynamics, decomposition, trace gas fluxes). Here we present results from a
      mesocosm experiment in which we assessed how the richness of emergent macrophyte
      functional groups influences aboveground and belowground plant growth and
      microbial-mediated functions related to carbon and nitrogen cycling, with an
      emphasis on methane (CH4) efflux and potential denitrification rates. We found
      that an increase in the richness of wetland plant functional groups enhanced
      belowground plant biomass, altered rooting patterns, and decreased methane
      efflux, while having no effect on aboveground plant production or denitrification
      potential. We hypothesize that the greater root production and increased rooting
      depth in the highest diversity treatments enhanced CH4 oxidation to a relatively
      greater degree than methane production, leading to an overall decrease in CH4
      efflux across our plant functional group richness gradient.

PMID- 18051660
TI  - Influence of fish on habitat choice of water birds: a whole system experiment.
AB  - It is notoriously difficult to study population interactions among highly mobile
      animals that cannot be meaningfully confined to experimental plots of limited
      size. For example, migratory water birds are believed to suffer from competition
      with resident fish populations for shared food resources. While observational
      evidence in support of this hypothesis is accumulating, replicated experiments
      addressing this issue at the proper spatial scale are lacking. Here, we report
      from a replicated whole-system experiment in which we stocked large (0.07 km2),
      shallow (< or =2.5 m deep), highly eutrophic ponds in the bird protection area
      "Ismaninger Speichersee mit Fischteichen" with different densities of carp and
      assessed the responses of water birds and their food resources during summer over
      several years. In all years, the biomasses of benthic macroinvertebrates,
      macroalgae, and macrophytes as well as the densities of herbivorous, carnivorous,
      and omnivorous water birds were reduced in carp ponds compared to fishless ponds.
      The negative effects of carp on food resources and on the numbers of water birds
      feeding in carp ponds increased over the season (May-September) and were stronger
      at high than at low stocking densities of carp. Consequently, differences in
      resource densities between ponds with and without carp increased, and the ranking
      of ponds with respect to resource densities became more predictable over the
      season. These factors may have contributed to a seasonal improvement of the
      birds' abilities to track resource densities across ponds, as suggested by tight
      correlations of bird numbers on ponds with resource densities late, but not
      early, in the season.

PMID- 18051661
TI  - Avian herbivory: an experiment, a field test, and an allometric comparison with
      mammals.
AB  - Mechanistic studies on herbivore functional responses have largely taken place in
      mammals; very little has been done in herbivorous birds so far. Here we aim to
      fill that gap by experimentally quantifying the (short-term) functional response
      of a large avian herbivore, the Bewick's Swan (Cygnus columbianus bewickii). We
      explicitly distinguish between encounter-limited and handling-limited foraging by
      analyzing the results in the framework of the models of D. E. Spalinger and N. T.
      Hobbs, originally developed for mammalian herbivory. Bite size in captive swans
      was experimentally manipulated by varying sward height. The time interval between
      two bites increased with bite size, which supports the handling-limited model
      (process 3) and rejects the encounter-limited models (processes 1 and 2).
      Subsequently, we took the obtained functional response parameters into the field
      in order to predict, from measurements of sward height, (1) bite sizes, (2)
      handling times, and (3) short-term intake rates in free-ranging swans. Indeed,
      for all three variables, the observed values closely matched the experimentally
      based predictions. Finally, we review functional response parameters available in
      the literature on avian herbivores and scale them allometrically in relation to
      mammals. This analysis revealed that maximum bite sizes, and therefore maximum
      intake rates, in herbivorous birds are smaller than in herbivorous mammals. We
      hypothesize and provide evidence that birds compensate by longer daily foraging
      times.

PMID- 18051662
TI  - Flightlessness and the energetic cost of wing molt in a large sea duck.
AB  - Although the replacement of feathers apparently represents the major event of
      somatic production in the annual cycle of wild birds, knowledge about the
      energetics of molt has always been hampered by logistical and technical
      difficulties, which are exacerbated by the fact that birds are able to compensate
      behaviorally to buffer any variation in energy demand. During wing molt, sea
      ducks (Mergini) and other diving birds lose all of their wing feathers at once,
      leading to a period of temporary flightlessness of variable duration, a condition
      that considerably restricts their movements and increases the probability of
      predation. In the present study, we present the first results aimed at
      quantifying the duration of flightlessness, energy expenditure, and foraging
      effort during molt of a wing-propelled diving bird, the Common Eider (Somateria
      mollissima). Data loggers were implanted in the body cavity of 13 females to
      record heart rate and hydrostatic pressure (depth) every two seconds for a period
      of 220 days. Flight frequency and duration were assessed from elevated and
      constant heart rate, and the absence of flight was used to quantify the duration
      of flightlessness, which lasted, on average, 36 +/- 8 days (mean +/- SD). Using a
      period of four weeks before and four weeks after the flightless period, we found
      that dive depth (ranging from 1 to 2 m, on average) and daily diving time did not
      vary during the course of the study. Daily metabolic rate increased by 9%, and
      resting metabolic rate by 12% from the pre-molt period to the flightless period
      and remained high during the post-molt period. This study indicates that the
      energetic costs of replacing flight remiges in female eiders are substantial,
      although this is not associated with any change in foraging effort, which
      suggests that female Common Eiders lose mass during wing molt. Finally, estimates
      of energy savings associated with the total absence of flights during wing molt
      represent 6% of daily metabolic rate or 14% of resting metabolic rate. This
      finding contrasts with the classical view that little or no benefit is associated
      with a flightless condition. We suggest that such energy savings may have favored
      the evolution of temporary flightlessness in diving birds.

PMID- 18051663
TI  - Age and race, BMI and CVD mortality.

PMID- 18051664
TI  - Evaluating accountability in the Vaccines for Children program: protecting a
      federal investment.
AB  - The Vaccines for Children (VFC) program supplies health-care providers with
      federally purchased vaccines at no cost for administration to eligible children.
      Evaluation of vaccine accountability activities ensures appropriate and timely
      vaccinations are delivered. Program grantees in 50 states, Washington, five large
      U.S. metropolitan cities, and five U.S. territories and possessions completed a
      Web-based survey between December 2002 and January 2003 focused on current
      vaccine accountability operational systems. Most grantees required providers to
      complete profiles describing the vaccination needs and demographics of their
      practices. More than half requested providers use benchmarking data, doses
      administered reports, and/or claims or encounter data to determine their VFC
      program-eligible population size; however, > 65% did not have written procedures
      for investigating and reconciling discrepancies between estimated vaccine needs
      and actual vaccine-use data. Most grantees had written standard policies
      requiring providers to report vaccine loss and wastage routinely and to explain
      why they occurred. Ninety percent of grantees did not have procedures to check
      providers for fraud and abuse sanctions, and 52% did not have written procedures
      to address complaints of vaccine fraud and abuse. These results suggested
      specific areas in which the Centers for Disease Control and Prevention should
      work with grantees to improve vaccine accountability practices. As a result,
      enhancements to the VFC program are being implemented to address these areas and
      their impact evaluated for their effectiveness in ensuring the continued success
      of the VFC program in protecting the nation's most vulnerable children and
      adolescents.

PMID- 18051665
TI  - Respiratory protection programs for firefighters: a survey of practices for the
      state of Kentucky.
AB  - OBJECTIVE: Firefighters play a crucial role as first responders in a variety of
      situations that can expose them to respiratory hazards. To ensure their safety
      and health, fire departments should have a respiratory protection program in
      place for all firefighters. A survey of Kentucky fire departments was conducted
      to assess their respiratory protection practices, barriers to program
      implementation, and medical evaluation programs. METHOD: A 21-question survey
      assessing respiratory practices during the previous 12 months was mailed to all
      Kentucky fire departments. RESULTS: A 62% survey response rate was achieved, with
      116 of Kentucky's 120 counties returning at least one survey. All respondents
      indicated they were utilizing some type of respiratory protection, but only 37%
      indicated they had a written respiratory protection program. Compensation status
      and department sizes were found to be significant variables (p < 0.01) in
      determining if a fire department had a written respiratory protection program.
      Lack of funding (48%) and lack of understanding (39%) were cited as the greatest
      barriers to program implementation. Only 51% indicated they require their
      firefighters to receive a fit testing of their respirator, and 23% indicated they
      had a health-care provider who reviewed medical questionnaires or provided
      medical evaluations. CONCLUSION: This survey indicates that many Kentucky fire
      departments are not meeting the legal and voluntary respiratory protection
      standards and guidelines, and demonstrates the need for improved education and
      funding to ensure that firefighters are adequately protected from respiratory
      hazards. This is particularly applicable to small rural volunteer departments,
      which had the greatest gap in compliance.

PMID- 18051666
TI  - Comparison of health and social characteristics of people leaving New York City
      jails by age, gender, and race/ethnicity: implications for public health
      interventions.
AB  - OBJECTIVES: We compared health and social needs by gender, age, and race/
      ethnicity of people leaving New York City jails and assessed the implication of
      these differences for the development of jail reentry programs. METHODS: Surveys
      were completed with 1,946 individuals (536 men, 704 women, and 706 adolescent
      males) between 1997 and 2004. Structured questionnaires captured data on
      demographic, criminal justice, substance use, and health characteristics.
      Bivariate comparisons were performed to determine variations between men and
      women, men and male adolescents, and non-Latino black and Hispanic/Latino
      respondents. RESULTS: The majority of participants were black and
      Hispanic/Latino, reported high levels of substance use, had high rates of
      recidivism, and experienced difficult living circumstances. Compared with men,
      women were more likely to be homeless, use illicit drugs, report drug charges at
      index arrest, have health problems, and be parents. Adolescent males were more
      likely than men to rely on illegal activities for income and to have used
      marijuana and alcohol recently, and were less likely to report homelessness or
      health problems. Ethnic/racial differences between black and Hispanic/Latino
      respondents within gender and age groups were smaller than differences among
      these groups. CONCLUSIONS: Jails concentrate individuals with multifaceted health
      and social problems, providing opportunities to engage at-risk populations in
      comprehensive reentry programs. Gender, age, and ethnic/racial differences among
      incarcerated populations require that interventions be tailored to the specific
      needs of these different groups.

PMID- 18051667
TI  - Impact of a smoke-free hospital campus policy on employee and consumer behavior.
AB  - OBJECTIVE: Although smoke-free hospital campuses can provide a strong health
      message and protect patients, they are few in number due to employee retention
      and public relations concerns. We evaluated the effects of implementing a clean
      air policy on employee attitudes, recruitment, and retention; hospital
      utilization; and consumer satisfaction in 2003 through 2005. METHODS: We
      conducted research at a university hospital campus with supplemental data from an
      affiliated hospital campus. Our evaluation included (1) measurement of employee
      attitudes during the year before and year after policy implementation using a
      cross-sectional, anonymous survey; (2) focus group discussions held with
      supervisors and security personnel; and (3) key informant interviews conducted
      with administrators. Secondary analysis included review of employment records and
      exit interviews, and monitoring of hospital utilization and patient satisfaction
      data. RESULTS: Employee attitudes toward the policy were supportive (83.3%) at
      both institutions and increased significantly (89.8%) at post-test at the
      university hospital campus. Qualitatively, administrator and supervisor attitudes
      were similarly favorable. There was no evidence on either campus of an increase
      in employee separations or a decrease in new hiring after the policy was
      implemented. On neither campus was there a change in bed occupancy or mean daily
      census. Standard measures of consumer satisfaction were also unchanged at both
      sites. CONCLUSION: A campus-wide smoke-free policy had no detrimental effect on
      measures of employee or consumer attitudes or behaviors.

PMID- 18051668
TI  - Potential implications of missing income data in population-based surveys: an
      example from a postpartum survey in California.
AB  - OBJECTIVES: Income data are often missing for substantial proportions of survey
      participants and these records are often dropped from analyses. To explore the
      implications of excluding records with missing income, we examined
      characteristics of survey participants with and without income information.
      METHODS: Using statewide population-based postpartum survey data from the
      California Maternal and Infant Health Assessment, we compared the age, education,
      parity, marital status, timely prenatal care initiation, and neighborhood poverty
      characteristics of women with and without reported income data, overall, and by
      race/ethnicity/nativity. RESULTS: Overall, compared with respondents who reported
      income, respondents with missing income information generally appeared younger,
      less educated, and of lower parity. They were more likely to be unmarried, to
      have received delayed or no prenatal care, and to reside in poor neighborhoods;
      and they generally appeared more similar to lower- than higher-income women.
      However, the patterns appeared to vary by racial/ethnic/nativity group. For
      example, among U.S.-born African American women, the characteristics of the
      missing-income group were generally similar to those of low-income women, while
      European American women with missing income information more closely resembled
      their moderate-income counterparts. CONCLUSIONS: Respondents with missing income
      information may not be a random subset of population-based survey participants
      and may differ on other relevant sociodemographic characteristics. Before
      deciding how to deal analytically with missing income information, researchers
      should examine relevant characteristics and consider how different approaches
      could affect study findings. Particularly for ethnically diverse populations, we
      recommend including a missing income category or employing multiple-imputation
      techniques rather than excluding those records.

PMID- 18051669
TI  - Epidemiology of non-canine bite and sting injuries treated in U.S. emergency
      departments, 2001-2004.
AB  - OBJECTIVES: This study was conducted to estimate the burden of non-canine-related
      bite and sting injuries in the U.S.; describe the affected population, injury
      severity, and bite or sting source; and provide considerations for prevention
      strategies. METHODS: Data were from the 2001 through 2004 National Electronic
      Injury Surveillance System-All Injury Program (NEISS-AIP) (a stratified
      probability sample of U.S. hospitals). Records included information about age,
      body part affected, cause, diagnosis, disposition, and gender. Narrative
      descriptions were coded for the source of the bite or sting. RESULTS: Between
      2001 and 2004, an estimated 3.6 million people were treated in emergency
      departments for injuries related to non-canine bites and stings. Results detail
      the reported sources of the bite or sting, and examine sources by gender and age
      group. Common sources included bees (162,000 cases annually), spiders (123,000
      cases annually), and cats (66,000 cases annually). Female adults were more likely
      than male adults to be treated for cat bites. Although rare, of the known
      venomous snakebites, more than half (58.4%) of the patients were hospitalized.
      CONCLUSIONS: Our results demonstrate the public health burden of non-canine
      related bite and sting injuries. More than 900,000 people were treated in
      emergency departments annually for non-canine bite or sting injuries, or roughly
      1.7 injuries per minute. Treatment consumes substantial health-care resources.
      While preventing these injuries should be the first line of defense, resources
      could be conserved by educating the public about immediate first aid and when
      warning signs and symptoms indicate the need for professional or emergency care.

PMID- 18051670
TI  - Panel classification of self-reported exposure histories: a useful exposure index
      after a mass-casualty event.
AB  - OBJECTIVE: Although rapid epidemiologic investigations of toxic exposures require
      estimates of individual exposure levels, objective measures of exposure are often
      unavailable. We investigated whether self-reported exposure histories, when
      reviewed and classified by a panel of raters, provided a useful exposure metric.
      METHODS: A panel reviewed exposure histories as reported by people who
      experienced a chlorine release. The panelists received no information about
      health-care requirements or specific health effects. To each exposure case, each
      panelist assigned one of five possible exposure severity ratings. When assigned
      ratings were not in initial agreement, the panelists discussed the case and
      assigned a consensus rating. Percent agreement and kappa statistics assessed
      agreement among panelists, Kendall's W measured agreement among panelists in
      their overall ordering of the exposure histories, and Spearman's rho compared the
      resultant rankings with individual health outcome. RESULTS: In 48% of the cases,
      the panelists' initial ratings agreed completely. Overall, initial ratings for a
      given case matched the consensus rating 69% to 89% of the time. Pair-wise
      comparisons revealed 85% to 95% agreement among panelists, with weighted kappa
      statistics between 0.69 and 0.83. In their overall ranking of the exposure
      histories, the panelists reached significant agreement (W = 0.90, p < 0.0001).
      Disagreement arose most frequently regarding probable chlorine concentration and
      duration of exposure. This disagreement was most common when panelists
      differentiated between adjacent categories of intermediate exposure. Panel
      assigned exposure ratings significantly correlated with health outcome
      (Spearman's rho = 0.56; p < 0.0001). CONCLUSION: Epidemiologists and public
      health practitioners can elicit and review self-reported exposure histories and
      assign exposure severity ratings that predict medical outcome. When objective
      markers of exposure are unavailable, panel-assigned exposure ratings may be
      useful for rapid epidemiologic investigations.

PMID- 18051671
TI  - Rapid assessment of exposure to chlorine released from a train derailment and
      resulting health impact.
AB  - OBJECTIVES: After a train derailment released approximately 60 tons of chlorine
      from a ruptured tanker car, a multiagency team performed a rapid assessment of
      the health impact to determine morbidity caused by the chlorine and evaluate the
      effect of this mass-casualty event on health-care facilities. METHODS: A case was
      defined as death or illness related to chlorine exposure. Investigators gathered
      information on exposure, treatment received, and outcome through patient
      questionnaires and medical record review. An exposure severity rating was
      assigned to each patient based on description of exposure, distance from
      derailment, and duration of exposure. A case involving death or hospitalization >
      or = 3 nights was classified as a severe medical outcome. Logistic regression was
      used to examine factors associated with severe medical outcomes. RESULTS: Nine
      people died, 72 were hospitalized in nine hospitals, and 525 were examined as
      outpatients. Fifty-one people (8%) had a severe medical outcome. Of 263 emergency
      department visits within 24 hours of the incident, 146 (56%) were in Augusta,
      Georgia; at least 95 patients arrived at facilities in privately owned vehicles.
      Patients with moderate-to-extreme exposure were more likely to experience a
      severe medical outcome (relative risk: 15.2; 95% confidence interval 4.8, 47.8)
      than those with a lower rating. CONCLUSIONS: The rapid investigation revealed
      significant morbidity and mortality associated with an accidental release of
      chlorine gas. Key findings that should be addressed during facility, community,
      state, and regional mass-casualty planning include self-transport of symptomatic
      people for medical care and impact on health-care facilities over a wide
      geographic area.

PMID- 18051673
TI  - Lessons learned from the 1918-1919 influenza pandemic in Minneapolis and St.
      Paul, Minnesota.

PMID- 18051672
TI  - Evaluation findings from the Institute for Public Health and Faith
      Collaborations.
AB  - OBJECTIVE: The Institute for Public Health and Faith Collaborations sought to
      cultivate boundary leadership to strengthen collaboration across religious and
      health sectors to address health disparities. This article presents findings from
      an evaluation of the Institute and its impact on participating teams of faith and
      public health leaders. METHODS: . Self-administered surveys were completed by
      participating team members (n = 243) immediately post-Institute. Semistructured
      telephone interviews were conducted with at least one health and one faith leader
      per team six to eight months after the Institute. RESULTS: Significant self
      reported improvement occurred for all short-term outcomes assessed, with the
      largest increases in describing organizational frames and why they are important
      for community change, and understanding the role of boundary leaders in community
      systems change. Six months after the Institute, participants spoke of
      inspiration, team building, and understanding their own leadership strengths as
      important outcomes. Leadership growth centered on functioning in groups, making a
      change in their work, a renewed faith in self, and a renewed focus on applying
      themselves to faith/health work. Top team accomplishments included planning or
      implementing a program or event, or solidifying or sustaining a collaborative
      structure. The majority felt they were moving in the right direction to reduce
      health disparities, but had not yet made an impact. CONCLUSIONS: Results suggest
      the Institute played a role in helping to align faith and health assets in many
      of the participating teams.

PMID- 18051674
TI  - A model for enhancing evidence-based capacity to make informed policy decisions
      on the introduction of new vaccines in the Americas: PAHO's ProVac initiative.

PMID- 18051675
TI  - Massachusetts et al. v Environmental Protection Agency: implications for public
      health policy and practice.

PMID- 18051676
TI  - [Thyroid cancer incidence among Chernobyl emergency workers: follow-up period
      1986-2003].
AB  - A vast amount of research articles devoted to the increase in childhood thyroid
      cancer incidence in the most contaminated by radionuclides territories of
      Belarus, Russia and Ukraine affected by the Chernobyl accident were published
      recent years. However, the amount of research studies of thyroid cancer incidence
      among the Chernobyl emergency workers (liquidators) is quite scanty. In the
      article results of the study of thyroid cancer incidence in the cohort of the
      Chernobyl liquidators (103427 persons) residing in 6 administrative regions of
      Russia (North-West, Volgo-Vyatsky, Central-Chernozemny, Povolzhsky, North
      Caucasus and Urals) are described and discussed. For the period 1986-2003 eighty
      seven cases of thyroid cancer were detected in the cohort. Statistically
      significant excess of the incidence among liquidators over baseline incidence,
      SIR = 3.39 (95% CI: 2.73; 4.16), among men of Russia has been found. The highest
      thyroid cancer incidence (SIR = 6.49) was registered among liquidators who had
      been involved in mitigation works during April-July 1986. At the same time no
      statistically significant relationship between the incidence rate and external
      radiation dose, ERR = 1.68 (95% CI: -0.95; 6.46), was detected.

PMID- 18051677
TI  - [Postnatal effects in children irradiated during the intra-uterine development,
      as a result of failure at the Chernobyl NPP].
AB  - Somatic and genetic effects at children who have undergone the influence of
      ionizing radiation during in utero development and at the subsequent stages
      ontogenesis are investigated, in view of dozes of the general irradiation and
      equivalent dozes of an irradiation of red bone brain. 1144 children were
      examined: 1st group consisted of children who have been born from women pregnant
      at the moment of failure, evacuated from Pripyat; 2nd group included children who
      have been born from women pregnant at the moment of failure, stayed to live in a
      zone of the strict radiation control; 3rd group was the control group--children
      who have been born in 1986, living in safe region of the Ukraine according to
      radiation conditions. The presence of direct correlation link between quantity of
      small anomalies of the development and the total radiation dose of the fetus (R =
      0.61, p < 0.002) and inverse link with fetus age at the moment of radiation
      factor effect (R = -0.53, p < 0.003) has been established. Significant
      correlation links between the total radiation dose and the level of children
      health (R = 0.45, p < 0.03); the equivalent radiation dose of the red bone marrow
      and the frequency of damages in the chromosomal apparatus of the somatic cells
      (1st group--R = 0.51, p < 0.02; 2nd group--R = 0.62, p < 0.002) have been
      revealed.

PMID- 18051679
TI  - [Development of radioadaptive properties for microscopic fungi, long time located
      on terrains with a heightened background radiation after emergency on Chernobyl
      NPP].
AB  - In 7 species of micromycetes which were isolated from radioactive contaminated
      areas of Chernobyl NPP zone under exposure of two artificial sources: y-low
      energy (121Sn) and radiation mix type gamma + beta (137Cs). Two new earlier
      unknown radioadaptive properties for fungi--radiotropism and radiostimulation
      were established. The strains, which were isolated from clean areas, did not have
      such features. All investigated strains, which have shown positive radiotropism
      at the same time, have shown stimulation of conidia germination and of length of
      the emergent hyphum under exposure to one of sources of radiation. It was shown
      that micro fungi having radioadaptive properties, the adaptive response to high
      (100-1000 Gy) ionizing radiation doses was found that is evidence of that these
      strains have high radio resistance level. Nevertheless fungal strains have shown
      varied response to presence of ionizing radiation depending on its type and
      absorbed dose.

PMID- 18051678
TI  - [The estimation of 90Sr and 137Cs excretion parameters from the organism of wild
      and laboratory small mammals in vivo, after natural contamination of them in the
      Chernobyl zone].
AB  - In the course of laboratory experiment, parameters of 90Sr and 137Cs excretion
      were estimated in individuals of bank vole Clethrionomys glareolus, captured at
      one of the most contaminated sites of the Chernobyl zone. The animals were kept
      under laboratory conditions using "clean" feed during 50 days. The similar
      investigation was carried out with laboratory mice Mus musculus (Big Blue line)
      during a longer period (184 days). The measurements of 90Sr content in the
      animals' body were in vivo carried out, using a specially designed beta
      spectrometer with appropriate software, and 137Cs one--by the gamma-spectrometer.
      During the experiment, the animals had lost less 0.4% of activity due to physical
      decay of radionuclides. The organism was depurated mainly through biological
      excretion. In accordance with parameters of one-component exponential decay
      equation, 99.3% of 137Cs initial content in vole was excreted with half-life
      period of 2.18 days, and mice--4.4 days (99%). 90Sr excretion had longer half
      life period: 11.7 days (56%) in voles, and 49.9 days (87%) in laboratory mice.
      The rest radionuclides amount of given model was considered as non-excreted from
      the organism during the observation period. It was determined on the example of
      voles that 90Sr and 137Cs loss in males was faster than in females, and among
      females more intensive excretion was in lactating females. 137Cs excretion from
      the body of bank vole is mainly with urine (74.7%), whereas 90Sr one--with feces
      and urine in approximately equal amounts. Due to the birth of babies and
      consequent feeding female lose appreciably less amount of radionuclides body
      burden than at daily loss with urine and feces.

PMID- 18051680
TI  - [The adaptive response of first generation offsprings irradiated parents].
AB  - In offspring's of first generation irradiated inhabitants of Techa river
      (fathers, mothers and both parents) the spontaneous level of damaged blood
      lymphocytes, sensitivity of lymphocytes to the additional acute irradiation in
      dose 1.0 Gy and radioinduced adaptive response after adaptive (5 cGy) and
      challenge (1.0 Gy) irradiation 5 h after was studied. The micronuclei test with
      cytochalasin B as a criteria of the effect have been used. It was shown, that
      descendents of irradiated parents differ from the control group. The main
      difference is the significant decrease of the adaptive response frequency in the
      progeny. In the offspring's of the irradiated fathers and mothers there is no one
      individuals with the adaptive response; in the offspring's of both irradiated
      parents the frequency of individuals with adaptive response decreases in control
      from 19.5% to 6.8%. The distribution of descendents according to response on
      adaptive irradiation differ significantly from the control distribution and from
      the each other. And the tendency to the radiosensitivity increase after adaptive
      irradiation was observed. In the whole joint group of progeny the mean
      spontaneous cell frequency with micronuclei decreased, but the sensitivity of
      lymphocytes to the additional acute irradiation doesn't differ from the control.
      The results of the paper permit to suppose that transgenerational genome
      instability in human can be determined. Earlier discovered decrease of the
      adaptive response frequency in the Techa river livings is observed in the
      offspring's of irradiated fathers, mothers and both parents.

PMID- 18051681
TI  - [The effects of chronic radiation exposure on the frequency of mutations at
      minisatellite DNA loci in residents of the Techa Riverside Villages].
AB  - The frequency of mutations at eight minisatellite DNA loci (B6.7, CEB1, CEB15,
      CEB25, CEB 36, MS1, MS31 and MS32) in peripheral blood cells were assessed for
      exposed residents of the Techa riverside villages as a function of individual
      exposure doses. The frequency of minisatellite mutations was found to be
      significantly higher in male gametes than in female ones; no clear-cut dose
      effect relationship was traced. There was no evidence of dependence of mutation
      frequency on exposure dose rates in the year of conception, the offspring's
      intrauterine red bone marrow dose and soft tissues doses.

PMID- 18051682
TI  - [The phenomenon of the single-strand DNA breaks level decrease in blood system
      cells in first generation chronically irradiated mice].
AB  - For the first time has been shown experimentally that chronic low dose-rate gamma
      radiation (0.04 mGy/hr) exposure leads to decrease of the single-strand DNA
      breaks level in spleen cells in 2.3 times (p < 0.001) and blood leukocytes in 6.1
      times (p < 0.01), a decrease of the apoptotic cells frequency in 1.3 times (p <
      0.05) and an increase in the spleen relative mass ratio B 1.2 times (p < 0.001)
      in CBA mice offspings (F1) from the chronically irradiated parents and exposed to
      chronic irradiation during the embryonic and postembryonic periods. A hypothesis
      about the more compact chromatin structure of blood system cells in the
      individuals of the first generation from chronically irradiated mice is proposed.

PMID- 18051683
TI  - [The influence of low doze gamma-irradiation on life span of Drosophila mutants
      with defects of DNA damage sensation and repair].
AB  - It was shown that life span of wild type strain Canton-S increased after low doze
      gamma-irradiation. It was revealed the decrease of life span after irradiation in
      Drosophila mutants with defects of DNA damage sensation and repair genes mei-9
      and mei-41, both in homozygous and heterozygous lines. In mei-41 line males'
      lives longer than females in contrast to other lines.

PMID- 18051684
TI  - [The effect of low-dose rate radiation simulating the high-altitude flight
      conditions on mice in vivo].
AB  - In present work, we investigated the peculiarities of the effect of a low-dose
      rate high-LET radiation that simulates the spectral and component composition of
      the radiation field formed in the atmosphere at a height of 10 km on mice in
      vivo. The dose dependence and adaptive response were examined. Irradiation of
      mice was performed for 24 h a day in the radiation field behind the concrete
      shield of the Serpukhov accelerator of 70 GeV protons for the time (15-31 days)
      necessary to accumulate the required doses. The experiments demonstrated that
      irradiation of mice in vivo in the dose range of 11.5-31.5 cGy leads to an
      increase in cytogenetic damage to bone marrow cells and induces no adaptive
      response in bone marrow cells.

PMID- 18051685
TI  - [The hormonal and genetic effects induced by an irradiation in small dozes at
      Tradescantia (a clone 02)].
AB  - The purpose of the present work was studying the possible interrelation of the
      hormonal status of plants and size of the genetic effects induced by an
      irradiation in small dozes. The frequency of somatic mutations in strings
      Tradescantia (a clone 02) at an irradiation in dozes up to 28 cGy was estimated.
      Influence radiations in a range from background up to 28 cGy on the maintenance
      in inflorescences Tradescantia (a clone 02) the basic groups of plant hormones is
      investigated: abscisic acid, cytokinin, auxin and gibberellin A3. It is shown,
      that small dozes of an irradiation cause extremely radical changes of hormonal
      balance in fabrics of inflorescences Tradescantia. Received results are discussed
      with attraction of the data on influence phytohormones on kinetics a cellular
      cycle.

PMID- 18051686
TI  - [The recovery parameters of DNA strand breaks of Ehrlich ascites cells after the
      combined action of ionizing radiation and hyperthermia].
AB  - A mathematical model of DNA strand breaks postirradiation repair and the
      methodology allowing to differentiate the mechanism of inhibition of DNA strand
      breaks recovery after combined actions of ionizing radiation and hyperthermia
      have been described in this paper. Using this model and the results published by
      other authors for DNA strand breaks of Ehrlich ascites cells, there have been
      obtained the data showing that the portion of DNA-damages that the cell incapable
      to recover after consecutive thermoradiation action was risen with an increase in
      thermal load under insignificant change of repair constant. It means the
      mechanism of DNA strand breaks recovery inhibition is realized in a greater
      extent through the formation of irreversible damages but not through the damage
      of repair process itself.

PMID- 18051687
TI  - [The prognosis of the portion of irreversible radiation damages after
      simultaneous action of hyperthermia and ionizing radiation on yeast cells].
AB  - The results of experimental research of diploid yeasts cells survival after
      simultaneous action of hyperthermia and ionizing radiation (60Co) have been
      described. It was shown that the cell ability to liquid holding recovery
      decreased with an increase in the temperature, at which the exposure was carried
      out. due to the increase in the irreversible component determining the relative
      part of radiation damage which cells are incapable to recover. To predict
      theoretically the relative part of irreversible radiation damage after combined
      action, the mathematical model was suggested taking into account the synergistic
      interaction of agents. Good correlation between experimental results and model
      prediction was demonstrated. The importance of the results obtained for the
      interpretation of the mechanism of synergistic interaction of various factors is
      discussed.

PMID- 18051688
TI  - [Study of dose-rate effects of neutron radiation in a wild-type and a repair
      deficient yeasts saccharomyces].
AB  - We report here a comparative analysis of RBE for lethality of a single pulse
      (duration 65 micros) of fast neutron with ultra high dose rates (up to 6 x 10(6)
      Gy/s) and continuous neutron radiation (3.6 x 10(3) s) of the pulse reactor BARS
      6. Three diploid strains, one haploid strain and three diploid repair-deficient
      strains (rad52-1/rad52-1; rad54/rad54; rad2/rad2) were used. The RBE values
      (D(0gamma)/1D(0n)) of a single pulse and continuous neutron irradiation were
      equal (1.7-1.8) with maximum RBE (4.1-3.1) in region of low doses (shoulder
      region). Haploid cells were found to be more (3 times) sensitive to both gamma
      rays and neutrons than the wild type. There was no obvious decrease in the RBE of
      1.9 in highly sensitive haploid cells as compared with highly resistant diploid
      cells. The repair-deficient strains (rad52-1/rad52-1; rad54/rad54) were more (up
      to 10 fold) sensitive to both neutrons and gamma-rays as compared with their
      parent line. The RBE values of 1.5-1.7 of neutrons for these mutants (independent
      by of the mode of irradiation) were found. The repair-deficient mutant rad2/rad2
      had similar sensitivity as a wild type and a RBE value was 2.0. We have concluded
      that biological effectiveness of the neutrons of pulse reactor BARS-6 was
      independent of the dose-rate, differing up to 10(8) fold. The RBE didn't vary
      significantly with the capacity of cells to repair DNA damages.

PMID- 18051689
TI  - [The assessment of biocenosis contamination in the region of radioactive waste
      storage (RWS) placing and influence of this storage on rodents].
AB  - The results of radiative and of chemical monitoring show definite contamination
      of this zone by 90Sr and toxic metals. The essential local contaminations of
      geosystems (up to 2.3 x 10(4) Bk/kg of soil) require in environmental condition
      assessment at biocenosis level. Biotesting found the increase of
      metallothioneines levels in kidney (up to 15.63 microg/g of tissue) and liver (up
      to 19.22 microg/g of tissue) of rodents inhabited in the region of RWS placing as
      compared with the control group (3.51 and 4.44 microg/g of tissue accordingly).
      Besides, the decrease of total quantity of leucocytes (by 14.5% as compared with
      the control group) and absolute quantity all forms of them in animal blood were
      noted. It was assumed the increase of protein--MT is the result of complex
      influence by ionizing radiation and toxic metals.

PMID- 18051690
TI  - [The concentration and distribution of 137Cs in soils of forest and agricultural
      ecosystems of Tula Region].
AB  - The paper deals with a comparative study of 137Cs contamination in forest, old
      arable and cultivated soils of Tula Region. Initial interception of Chernobyl
      derived 137Cs is higher in forest ecosystems: oak-forest > birch-forest > pine
      forest > agricultural ecosystems. Vertical migration of 137Cs in deeper layers of
      soils was intensive in agricultural ecosystems: cultivated soils > old arable
      soils > birch-forest soils > oak-forest soils > pine-forest soils. In study have
      been evaluated spatial variability of 137Cs in soil and asymmetrical
      distribution, that is a skew to the right. Spatial heterogeneity of 137Cs in
      agricultural soils is much lower than in forest soils. For cultivated soil are
      determined the rate of resuspension, which equal to 6.1 x 10(-4) day(-1). For
      forest soils are described the 137Cs concentration in litter of different
      ecosystems. The role of main accumulation and barrier of 137Cs retain higher
      layers of soils (horizon A1(A1E) in forest, horizon Ap in agricultural
      ecosystems) in long-term forecast after Chernobyl accident.

PMID- 18051691
TI  - [The accumulation of radionuclides 137Cs and 90Sr by different kinds and grades
      legumes crops].
AB  - The decision of protein problem on contaminated by radionuclides territories as a
      result of the accident on Chernobyl NPP is not possible without increase of the
      sowing areas legumes crops (peas, lupine, soybean). Introduction in agricultural
      manufacture of grades with a low level of accumulation radionuclides (peas--Aist,
      Polesskay, Gomelskay Agat; soybean--Severnaya zvezda, Mageva) will allow to
      receive agricultural production adequate "Republican allowable levels of the
      contents of 137Cs and 90Sr in agricultural raw material and forages" on arable
      lands at their higher density of radioactive contamination: 137Cs--1300-1480
      kBq/m2 (35.0-40.0 Ci/km2): 90Sr--18.5-37.0 kBq/m2 (0.50-1.00 Ci/km2).

PMID- 18051692
TI  - Every day brings a first impression.

PMID- 18051693
TI  - Just a minute.

PMID- 18051694
TI  - A tribute to the Calgary Family Nursing Unit: lessons that go beyond family
      nursing.

PMID- 18051695
TI  - Darwin's surprise: why are evolutionary biologists bringing back extinct deadly
      viruses?

PMID- 18051696
TI  - Poverty and human development.

PMID- 18051697
TI  - Clinical utility of B-type natriuretic peptide in early severe sepsis and septic
      shock.
AB  - B-type natriuretic peptide (BNP) has diagnostic, therapeutic, and prognostic
      utility in critically ill patients. For severe sepsis and septic shock patients
      in particular, similar clinical utility from the most proximal aspects of
      hospital presentation to the intensive care unit has not been examined. BNP
      levels were measured at 0, 3, 6, 12, 24, 36, 48, 60, and 72 hours in 252 patients
      presenting to the emergency department with severe sepsis and septic shock. The
      clinicians were blinded to the BNP levels. Elevated BNP levels (>100 pg/mL) were
      seen in 42% and 69% of patients on presentation and at 24 hours, respectively.
      Elevated BNP ranges (>230 pg/mL) were significantly associated with myocardial
      dysfunction and severity of global tissue hypoxia. When adjusted for age, gender,
      history of heart failure, renal function, organ dysfunction, and mean arterial
      pressure, a BNP greater than 210 pg/mL at 24 hours was the most significant
      independent indicator of increased mortality: odds ratio 1.061 (1.026-1.097), P <
      .001, 95% confidence interval. Patients with severe sepsis and septic shock often
      have elevated BNP levels, which are significantly associated with organ and
      myocardial dysfunction, global tissue hypoxia, and mortality. Serial BNP levels
      may be a useful adjunct in the early detection, stratification, treatment, and
      prognostication of high-risk patients.

PMID- 18051698
TI  - The effect of wild type P53 gene transfer on growth properties and tumorigenicity
      of PANC-1 tumor cell line.
AB  - BACKGROUND: The p53 protein function is essential for the maintenance of the
      nontumorigenic cell phenotype. Pancreatic tumor cells show a very high frequency
      of p53 mutation. To determine if restoration of wild type p53 function can be
      used to eliminate the tumorigenic phenotype in these cells, pancreatic tumor cell
      lines, PANC-1 and HTB80, differing in p53 status were stably transfected with
      exogenous wild type p53 gene. METHODS: The transfection was performed using
      Polybrene/DMSO-Assisted Gene Transfer method. The wild type p53 gene integration
      into genomic DNA was detected by Southern blot and PCR. Furthermore, the
      expression of wild type p53 protein was detected in selected clones by
      immunohistochemistry and Western blot. RESULTS: While HTB80 cell line failed to
      produce a stable p53 expressing clone, the PANC-1 cells produced stable lines.
      Following characterization of clones, the growth rate and tumorigenicity of PANC
      1 wild type p53 clones were compared to the control cells. Our data showed that
      the expression of wild type p53 decreased the growth rate of PANC-1 cells. It was
      also observed that the expression of wild type p53 in PANC-1 cells suppressed its
      potential for tumor formation in nude mice, completely, while the parental line
      leads to the formation of a relatively large tumor. CONCLUSION: Our results
      suggest that gene therapy based on restoration of wild type p53 protein function
      in pancreatic tumor cells with high amount of mutant p53 is a feasible option in
      pancreatic cancer treatment.

PMID- 18051699
TI  - Differential expression of rheumatoid factor-associated cross-reactive idiotypes
      in Iranian seropositive and seronegative patients with rheumatoid arthritis.
AB  - INTRODUCTION: High levels of rheumatoid factors (RF) are detectable in serum of
      the majority of patients with rheumatoid arthritis (RA), but 5-10% of patients
      remain seronegative (SN). Despite clinical and genetic similarities between these
      two subsets of RA, it has been proposed that they may be regarded as distinct
      clinical entities. METHODS: In the present study a panel of monoclonal antibodies
      (mAb) recognizing RF-associated cross-reactive idiotypes (CRI) linked to the VH1
      (G8), VH4 (LC1), VK3b (17-109) and a mAb recognizing the VK3 subgroup (C7) of
      immunoglobulin variable region (IgV) gene products were used to quantitate the
      level of expression of these gene products in serum and synovial fluid of 35
      seropositive (SP) and 8 SN RA patients by capture ELISA. RESULTS: While the
      concentration and relative proportion of the IgV are recognized by the mAb G8, 17
      109 and C7 were significantly higher in serum and synovial fluid of the SP RA,
      compared to the SN-RA patients (G8, p = 0.009; 17-109, p = 0.0001; C7, p =
      0.001). The CRI recognized by the mAb LC1 was highly represented in serum and
      synovial fluid of the SN-RA patients. There have been no significant differences
      in the level of expression of these IgV gene products (other than the product
      recognized by C7 mAb in SP patients) between serum and synovial fluid of either
      group of patients. CONCLUSION: Our results suggest that the expressed repertoire
      of Ig VH and VK genes in these two subsets of RA is differentially regulated and
      may be influenced by selective mechanisms leading to positive or negative
      selection of certain genes.

PMID- 18051700
TI  - Assessment of morphological and functional changes in the mouse testis and
      epididymal sperms following busulfan treatment.
AB  - BACKGROUND: Busulfan, a cytotoxic drug, which is currently used as a
      chemotherapeutic agent, has many side effects on different body organs. In this
      research, the effects of busulfan on sperm parameters and microstructure of mouse
      testis were investigated. METHODS: Busulfan was injected intrapretoneally at 10,
      20, 30, 40 and 50 mg/kg and testes were removed after 4, 6 and 8 weeks, weighed
      and processed for light microscopic examination. Transverse and cross section
      diameters of testes, seminiferous tubules diameters, percentage of different
      types of tubules, epithelium thickness, spermatogenic cell numbers and capsule
      thickness as well as the sperm parameters in epididymis were measured. RESULTS:
      There was a significant decline in sperm numbers and marked changes in testes
      structures. Almost 8 weeks after the injection of drug, some of the changes are
      reversed. Accordingly, the changes in percent of normal tubules without sperm,
      abnormal tubules and capsule thickness were increased until 6 weeks of drug
      administration, the changes declined thereafter. CONCLUSION: In general, busulfan
      caused a decrease in all analyzed parameters (except capsule thickness, normal
      tubules without sperm and abnormal tubules), probably due to the arrest of
      spermatogenesis. Our results also revealed that some of the changes are
      reversible and dose dependent.

PMID- 18051701
TI  - Identification of Mycobacterium tuberculosis CTL epitopes restricted by HLA
      A*0201 in HHD mice.
AB  - BACKGROUND: CD8 T cells are thought to play an important role in protective
      immunity to tuberculosis. The major histocompatibility complex class I subtype
      HLA-A*0201 is one of the most prevalent class I alleles, with a frequency of over
      30% in most populations. HLA-A*0201 transgenic, H-2D(b)/mouse beta2-microglobulin
      double-knockout mice (HHD) which express human HLA-A*0201 but no mouse class 1,
      was shown to provide a powerful model for studying induction of HLA-A*0201
      restricted immune responses in vivo. METHODS: HHD mice were immunized with
      plasmid DNA encoding MPB51 by using a gene gun, and IFN-gamma production from the
      immune spleen cells was analyzed in response to a synthetic overlapping peptide
      library covering the mature MPB51 sequence. catatonic T lymphocytes (CTL)
      activity was measured using cytotoxicity assay and the three-color flowcytometry
      was used to reveal IFN-gamma-producing immune spleen cells. RESULTS: Our findings
      were shown that only one peptide, p51-70, appeared to stimulate the immune
      splenocytes to produce IFN-gamma. Flow cytometric analysis with intracellular IFN
      gamma and the T-cell phenotype revealed that the p51-70 peptide contains an
      immunodominant CD8+ T-cell epitope. Further analysis with computer-assisted
      algorithms permitted identification of a T-cell nona mer epitope, p54-62.
      Finally, we proved that the p54-62/HLA-A*0201 complex is strongly recognized by
      HLA class I-restricted CD8+ MPB5 1-specific CTL cells. CONCLUSION: These results
      suggest that vaccination with MPB51 gene elicited MPB51-specific CTL. In
      addition, the P54-62 epitope thus represent potential subunit component for the
      design of vaccines against tuberculosis.

PMID- 18051702
TI  - Depletion of serotonin synthesis with p-CPA pretreatment alters EEG in urethane
      anesthetized rats under whole body hyperthermia.
AB  - BACKGROUND: Serotonin is believed as an important factor in brain function. The
      role of serotonin in cerebral psycho-patho-physiology has already been well
      established. However, the function of serotonin antagonist in anesthetized
      subjects under hyperthermia has not been studied properly. METHODS: Experiments
      were performed in three groups of urethane-anesthetized rats, such as: (i)
      control group, (ii) whole body hyperthermia group and (iii) p-CPA (para
      Chlorophenylalanine) pretreated hyperthermia group. Hyperthermia was produced by
      subjecting the rats to high ambient temperature of 38 +/- 1 degrees C (relative
      humidity 45-50%). Each group was divided for EEG (electroencephalogram) study and
      for determination of edematous swelling in the brain. RESULTS: Urethane
      anesthetized rats under hyperthermia show highly significant reduction in their
      survival time. The body temperature recorded during the hyperthermia was observed
      with significant and linear rise with marked increase in brain water content,
      which was analyzed just after the death of the subjects. The results of the
      electroencephalographic study in urethane-anesthetized rats recorded before death
      indicate that brain function varies in systematic manner during hyperthermia as
      sequential changes in EEG patterns were observed. However, a serotonin
      antagonist, p-CPA pretreatment increases the survival time with significant
      reduction in edematous swelling in brain but it does not affect the relationship
      between the core body temperature and the brain cortical potentials as observed
      in urethane anesthetized subjects exposed to whole body hyperthermia. The core
      body temperature in p-CPA pretreated rats show non-linear relationship with
      respect to the exposure time as it was observed in drug untreated subjects.
      CONCLUSION: The findings of the present study indicate that although pretreatment
      of p-CPA in rats has a marked correlation between the extravasations of the blood
      brain barrier under hyperthermia but shows minimum effect on the EEG in a model
      of hyperthermia under irreversible anesthesia.

PMID- 18051703
TI  - A study of the oxidation-induced conformational and functional changes in
      neuroserpin.
AB  - BACKGROUND: Neuroserpin, a member of the Serine Proteinase Inhibitor (Serpin)
      superfamily, is known to be a neuroprotective factor in the focal ischemic stroke
      followed by reducing the microglial activation. Neuroserpin is a protein rich of
      methionine residues that can scavenge the free radical species which may increase
      its neuroprotective effect. On the other hand, the oxidative modifications of the
      amino acid residues in neuroserpin may lead to changes in its conformation and
      function. In this study, it was investigated the changes in the conformation and
      the function of the oxidized neuroserpin. METHODS: Neuroserpin expressed in E.
      coli, BL21 or M15 harboring plasmid pQE81L containing neuroserpin cDNA. Expressed
      neuroserpin was purified by resin sulfopropyl A50 precharged with 0.1 M NiSO4
      under denaturing condition. Neuroserpin was oxidized under oxidative stress
      condition in the presence of different concentration of hydrogen peroxide. The
      oxidation of neuroserpin was conveniently detected by a carbonyl content assay
      using 2, 4 dinitrophenylhydrazine. Changes in tertiary structure of neuroserpin
      were monitored by spectrofluorimeter to study the alteration of intrinsic
      fluorescence and also fluorescence of 8-anilinonaphthalin-1 sulfonic acid (ANS)
      in native and oxidized form of neuroserpin. RESULTS: Total expressed neuroserpin
      was estimated 4-5 mg/lit in 2XYT culture media. SDS-PAGE analysis of purified
      neuroserpin showed a single band which reflects the efficiency of the resin SP
      A50 for purification of the proteins containing 6xHis tag. Carbonyl content of
      oxidized and native neuroserpin was estimated 12.3 +/- 0.3 and 0.45 +/- 0.05,
      respectively. The inhibitory activity of oxidized neuroserpin decreased up to 40
      60% as compared with native form of neuroserpin. Intrinsic fluorescence and also
      the emission of ANS bind to the hydrophobic region of the protein altered from
      380 to 85 and in the case of ANS from 105 to 150 in oxidized and native form of
      neuroserpin, respectively. CONCLUSION: The decreased intrinsic fluorescence
      intensity, an enhancement in the fluorescence of ANS, and loss of the inhibitory
      activity up to 40-60% in neuroserpin, all suggested a conformational modification
      in the protein under the oxidative stress condition. Remaining the inhibitory
      activity of neuroserpin reflects that the protein tolerates the oxidative stress
      condition effectively.

PMID- 18051704
TI  - Comparing invasive and non-invasive of isolated Shigella flexneri by electron
      microscopy of cell culture, SDS-PAGE and Congo red method.
AB  - BACKGROUND: The aim of this study was to compare invasive and non-invasive
      strains of Shigella flexneri isolated from Tehran by a 120 kDa protein band by
      SDS-PAGE, electron microscopy of cell culture and Congo red dye methods. METHODS:
      S. flexneri strains were isolated by standard bacterial methods from fecal
      specimens of children attending to the 3 children's hospitals. Phenotype analysis
      for screening virulent of strains of S. flexneri was done on a plate of tryptic
      soy agar contained 0.003% Congo red dye. Whole membrane protein preparations were
      used to examine the protein profiles of the inner and outer membrane of these
      Gram-negative bacteria. The protein mixture was electrophoresed through a
      polyacrylamide gel. The gel was stained with Coomassie brilliant blue R250 and
      destained with ethanol and acetic acid. HeLa cell culture was done by two-step
      preparations: one for light microscopy and the other for electron microscopy.
      RESULTS: Some of S. flexneri (46%) were Congo red positive colonies. S. flexneri
      with negative Congo red phenotype could not enter the HeLa cell culture. A 120
      kDa protein band was found in 46% of these bacteria which could enter into HeLa
      cell culture. Pseudopod structures which facilitate bacterial cell-to-cell spread
      were readily identified by electron microscopy. DISCUSSION: Since the existence
      of 120-kDa protein band was corresponded to enter of S. flexneri into the HeLa
      cell culture and correlated with Congo red dye positive, for identification of
      invasive and non-invasive S. flexneri strains, the use of a 120-kDa protein band
      by SDS-PAGE or a simple, rapid and very cheap Congo red dye method is
      recommended. Because, there are some deaths due to Shigella sp. in our country,
      notification on the isolation of these bacteria in both children hospitals
      laboratories and private clinical laboratories is important.

PMID- 18051705
TI  - Intercellular trafficking of VP22, a herpes simplex virus type 1 tegument
      protein.
AB  - BACKGROUND: The herpes simplex virus type 1 (HSV-1) tegument protein, VP22 has
      been reported to have the property of intercellular transport. The previous
      studies have shown that following expression of a fusion protein containing VP22;
      it spreads to every cell in a monolayer and concentrates in the nucleus. In spite
      of these reports, some studies have shown that VP22 trafficking and its nucleus
      accumulation is an artifact and no improvement in translocation of proteins fused
      to VP22 has been detected. METHODS: To better understand about VP22
      translocation, VP22-GFP (Green Fluorescent Protein) vector was constructed and
      its nuclear accumulation, transportation to the nomtransfected cells and
      translocation between different cell types were studied by fluorescent
      microscope. RESULTS: VP22-fusion protein was detected in nontransfected cells
      which in some of them the fusion protein was shown in nucleus. CONCLUSION: The
      results demonstrated that VP22 can easily transport between different cells but
      nuclear accumulation of the protein is not common in all of the recipient cells.

PMID- 18051706
TI  - Distribution of hepatitis B virus (HBV) genotypes among HBV carriers in Isparta.
AB  - BACKGROUND: The aim of this study was to investigate the prevalence of hepatitis
      B virus (HBV) genotypes in Isparta, Southwest of Turkey, as well as the clinical
      features and transmission route for patients with HBV infections. METHODS:
      Patients (n = 135) with HBV infection were included in the study. Epidemiological
      and clinical data were obtained. HBV genotypes were determined with a preS2
      epitope ELISA kit. RESULTS: Although the HBV transmission route remained
      unidentified in 51.1% of the patients, blood contact was determined as the most
      common probable transmission route (38.5%). One hundred twenty-four (91.8%) of
      135 samples, could be genotyped. One hundred fifteen (85.1%) were genotyped as
      type D/E, six (4.4%) were genotyped as type A, two (1.4%) were genotyped as type
      C, and one (0.7%) were genotyped as type F. CONCLUSION: Genotype D/E is
      determined as the predominant HBV genotype circulating in Isparta, Southwest of
      Turkey. No relationship between genotypes and disease severity and transmission
      route has been detected.

PMID- 18051707
TI  - The effect of Teucrium polium (Calpoureh) on liver function, serum lipids and
      glucose in diabetic male rats.
AB  - BACKGROUND: Teucrium polium is an analgesic, antidiabetic and antilipeidemic
      herbal medicament. The aim of this survey was to evaluate the effect of aqueous
      extract T. polium on liver enzymes linked to liver dysfunction, serum lipids and
      glucose, in diabetic male rats. METHODS: A total of 20 Sprague-Dawly male rats
      became diabetic by intraperitoneal injection of streptozotocin (60 mg/kg). the
      animals were divided randomly into two groups. Experimental group was fed
      Teucrium polium (50 mg/kg) for a month but control group was received the same
      volume of distilled water. Liver enzymes, biochemical parameters (cholesterol,
      triglyceride, low density lipoprotein, alanine transaminase, aspartae
      transaminase) and glucose were measured by kinetic (Enzymatic) and colorimetric
      methods. Data obtained were analyzed and mean values were compared by paired
      student's t-test. The results were expressed as mean +/- SD. Significant
      differences were set at P < 0.05. RESULTS: Our results showed that in test group,
      serum glucose values decreased significantly (P < 0.05), but cholesterol,
      triglyceride, low density lipoprotein, alanine transaminase and aspartae
      transaminase increased significantly after use of T. polium (P < 0.05). This
      parameters value did not show any changes in control group. CONCLUSION: Although
      the aqueous extract of Teucrium polium has strong hypoglycemic properties in
      experimental animals, but because of some hepatotoxic effects, it is not suitable
      to use it in human as an antidiabetic agent.

PMID- 18051708
TI  - [Modern prevention strategies of cervical cancer].
AB  - Cervical cancer is the most common malignancy of the female genital tract. Its
      incidence is still increasing with lower average onset age. Mass screening should
      be above prevention and treatment, and three screening programs, including the
      optimal program, the general program, and the basic program, are currently
      adopted in China. Cervical intraepithelial neoplasia (CIN) , a precancerous
      lesion, can be confirmed by the combined use of cytology, colposcopy, and
      histology and then managed with standardized approach. Human papillomavirus (HPV)
      infection is an essential factor during the development of cervical cancer, and
      persistent infection of high-risk HPVs may lead to CIN and subsequently develop
      to cervical cancer. High-risk HPV detection can be used for screening,
      differentiation of the atypical squamous cells of undetermined significance/ low
      grade squamous intraepithelial lesion (ASCUS/LSIL) triage, and follow-up after
      treatment. The modern strategy of HPV infection is "to treat the disease, CIN,
      means to treat the virus, HPV". The licensing of HPV vaccine is an important
      event in cancer prevention, and this vaccine can be used for the primary
      prevention. However, early diagnosis and early treatment are still the most basic
      strategies for cervical cancer prevention and treatment.

PMID- 18051709
TI  - [Highly efficient expression of codon-optimized human papillomavirus 16 L2E7 gene
      in Escherichia coli].
AB  - OBJECTIVE: To enhance the expression level of human papillomavirus (HPV) 16 L2E7
      in Escherichia coli (E. coli), in aim of providing high-level expression of HPV16
      L2E7 strain for pre-clinical high-throughout production. METHODS: The whole L2E7
      gene was optimized by software of Synthetic Gene Designer, reflecting E. coli
      codon usage. Two parts of codon-optimized gene were cloned into pET9a vector step
      by step. The positive clone, which was sequenced to be corrected, was transfected
      to BL21 (DE3+) via isopropyl-beta-D-thiogalactoside (IPTG) induction. They
      produced the HPV16 L2E7 fusion protein, which was further detected by SDS-PAGE
      and Western blot. The induction temperature, induction time, and IPTG
      concentration were also optimized by a series of experiments. Further
      purification modes of this protein were also explored. RESULTS: Codon-optimized
      HPV16 L2E7 was highly expressed in E. coli. The target protein accounted for
      nearly 60% of the total cell extract. CONCLUSION: High-level expression of HPV16
      L2E7 was successfully constructed.

PMID- 18051710
TI  - [Linkage of modified human papillomavirus type 16 E7 to CD40 ligand enhances
      specific CD8+ T-lymphocyte induction and anti-tumour activity of DNA vaccine].
AB  - OBJECTIVE: To develop human papillomavirus (HPV) 16 DNA vaccine for the treatment
      of HPV16 infection and its related tumors. METHODS: HPV16 oncogene E7 was
      modified by combined approaches including insertion and replication of specific
      region of E7 gene, murine codon optimization, and point-mutation at transforming
      regions of the E7 protein. The resulting artificial gene, named as mE7, was
      obtained by gene synthesis. The mE7 gene was then genetically fused to murine
      CD40 ligand (CD40L) by overlapping PCR to form the mE7/CD40L fusion gene. The
      mE7/CD40L gene was inserted into pVR1012 plasmid and then immunized C57/BL6 mice
      intramuscularly. The E7-specific IFN-gamma-secreting CD8+ T cells were analyzed
      with EIISPOT, and E7-specific antibody was measured by indirect ELISA. FACS
      assays were performed to analyze the activation of E7-specific Th cells. Mice
      were vaccinated, followed by tumor challenged or challenged before immunization.
      Tumor growth was observed. RESULTS: The mE7 DNA vaccine elicited an increased E7
      specific antibody level (P < 0.01), E7-specific IFN-gamma-secreting CD8+ T (P <
      0.01), and CD4+ T cells number (P < 0.05), compared with those of mice immunized
      with wE7 gene. Furthermore, the mE7/CD40L DNA vaccine elicited an increased
      number of E7-specific IFN-gamma secreting CD8+ T cell compared with that of mice
      immunized with mE7 gene (P < 0.01); however, no significant differences were
      found between mice immunized with the mE7 gene and mE7/CD40L fusion gene in the
      E7-specific antibody production and Th cell activation. In the preventive
      experiment, all mice received the mE7 or mE7/CD40L remained tumor-free 7 weeks
      after challenges with TC-1 tumor cells, while the wE7 group exhibited tumor
      growth within 2 weeks. In the therapeutic experiment, all the mice in the wE7
      group exhibited tumor growth within 8 days, while among mice receiving the mE7
      and mE7/CD40L, 30% and 45% of mice remained tumor-free after TC-1 challenge,
      respectively. HE staining of tumor tissues showed copious lymphocytes
      infiltration around tumor cells in mE7 and mE7/CD40L mice with regression of
      tumor growth. CONCLUSIONS: The mE7 DNA vaccine increases the E7-specific humoral
      and cellular immune responses, and the fusion of CD40L to mE7 gene enhances the
      specific immune responses and anti-tumor effects against HPV16 E7-expressing
      murine tumors. mE7/CD40L may therefore be a suitable and promising target for
      HPV16 therapeutic vaccine.

PMID- 18051711
TI  - [Relationship between human papillomavirus 16 infection and the expression of
      p33(ING1b), human telomerase reverse transcriptase in cervical squamous cell
      carcinoma of Uygur female in Xinjiang Uygur Autonomous Region].
AB  - OBJECTIVE: To explore the relationship between human papillomavirus (HPV) 16
      infection and the expression of p33(ING1b), human telomerase reverse
      transcriptase (hTERT) in cervical squamous cell carcinoma of Uygur Female in
      Xinjiang Uygur Autonomous Region. METHODS: Polymerase chain reaction (PCR) and
      immunohistochemical methods were used to detect HPV16 infection and the
      expression of p33(ING1b) and hTERT in the normal control group (n=12), the
      patients with cervical intraepithelial neoplasm (CIN) (n=34), and the patients
      with cervical squamous cell carcinoma (SCC) (n=50). RESULTS: In the cervical
      tissues of Uygur female, the HPV16 infection rate was 0 in control group, 22.2%
      in the CIN 1 group, 44.0% in CIN 2 & CIN 3 group, and 74.0% in SCC group (P =
      0.000). The expression rate of p33(ING1b) decreased was 91.7% in control group,
      77.7% in CIN 1 group, 68.0% in CIN 2 & CIN 3 group, and 36.0% in SCC group (P =
      0. 000). The expression rate of hTERT was 50.0% in control group, 66.6% in CIN 1
      group, 88.0% in CIN 2 & CIN 3 group, and 94.0% in SCC group (P = 0.000). In the
      cervical tissues of Uygur female, the HPV16 infection rate was negatively
      correlated with the expression of p33(ING1b) (r = -0.294, P = 0.004), and was
      positively correlated with the expression of hTERT (r = 0.286, P = 0.005). The
      expression of p33(ING1b) was negatively correlated with the expression of hTERT
      (r = -0.361, P = 0.000). CONCLUSION: The infection of HPV 16 correlates with the
      decreased expression of p33(ING1b) and increased expression of hTERT in the
      cervical squamous cell carcinoma of Uygur female in Xinjiang.

PMID- 18051712
TI  - [Comparative proteome analysis of human papillomavirus-infected cervical
      specimens and the difference between the high- and low-risk genotypes of human
      papillomavirus].
AB  - OBJECTIVE: To perform an comparative proteome analysis of human papillomavirus
      infected cervical specimens and to investigate different expressions between high
      and low-risk genotypes. METHODS: The cervical specimens were divided into two
      groups (cervical intraepithelial neoplasia group and condyloma acuminatum group)
      according to their genotypes. Using comparative proteome technology, high-risk
      human papillomavirus-infected cervical intraepithelial neoplasia, low-risk human
      papillomavirus-infected condyloma acuminatum, and normal cervical intraepithelial
      tissue were compared. The differential expression protein spots were identified
      by mass spectrometry. RESULTS: Totally 26 differential spots were selected and
      analyzed, and 22 peptide mass fingerprints (PMF) maps were obtained by MALDI-TOF
      MS. Eighteen proteins were preliminarily identified after searching the NCBInr
      database. The function information of these 18 proteins mainly involved cell
      metabolism, signal transduction, cell secretion, cell cytoskeleton construction,
      cell proliferation, and apoptosis. CONCLUSION: The proteomic expressions after
      the cervical infection of high- or low-risk genotype of human papillomavirus are
      obviously different.

PMID- 18051713
TI  - [Clinical evaluation of the xMAP technology in detection of high-risk human
      papillomavirus].
AB  - OBJECTIVE: To evaluate the clinical application value of flexible multi-analyte
      profiling (xMAP) technology in detecting high-risk human papillomavirus (HR-HPV).
      METHODS: Totally 1 061 women, aged 21-65 years, were randomly enrolled into the
      study. Cervical exfoliated cells were used in xMAP technology and hybrid capture
      II (hc2). Pathological diagnosis was used as golden standard. Consistency of
      these two methods was assessed. RESULTS: The sensitivity and specificity of xMAP
      technology were 80.31% and 85.83%, respectively. The positive and negative
      predictive values were 44.5% and 96.9%, respectively. The Kappa value for
      consistency between xMAP technology and hc2 was 0.58. CONCLUSIONS: The
      specificity of xMAP technology is similar to hc2 test, but the sensitivity is
      inferior to hc2. However, these two methods show good consistency in the
      detection of HR-HPV.

PMID- 18051714
TI  - [Application of high-risk human papillomavirus testing in women with abnormal
      cytology].
AB  - OBJECTIVE: To detect the high-risk human papillomavirus (HPV) infectious
      condition in women with abnormal cytology and evaluate its values in the
      screening of high grade squamous intraepithelial lesion. METHODS: We used hybrid
      capture 2 (hc2) method to examine 949 patients with abnormal cervical cytology
      results [ > or =atypical squamous cells of undetermined significance (ASC-US)
      according to the 2001 The Bethesda System diagnosis criteria]. All subjects also
      received colposcopy for tissue studies. RESULTS: Among 949 patients with abnormal
      cytology, the diagnoses of atypical squamous cells (ASC), low grade squamous
      intraepithelial lesion (LSIL), and high grade squamous intraepithelial lesion
      (HSIL) were made in 432, 310, and 207 patients, respectively. The high-risk HPV
      positive rate in ASC, LSIL, and HSIL were 40.3%, 44.8%, and 89.4%, respectively.
      The numbers of patients with pathologically confirmed results of negative
      intraepithelial lesion or malignancy (NILM), cervical intraepithelial neoplasia
      1, 2, 3 (CIN 1, 2, 3), and squamous cell carcinoma (SCC) were 335, 388, 118, 101,
      and 7, and the high-risk HPV positive rate was 17.3%, 66.2%, 92.4%, 97.0%, and
      100%, respectively. Among patients with atypical squamous cells of undetermined
      significance (ASC-US), rate of HSIL in high-risk HPV positive group and negative
      group were 10.2% and 0.8%, respectively (P < 0.01). In screening HSIL, the
      sensitivities of cytology [ > or = ASC cannot exclude HSIL (ASC-H)] and cytology
      ( > or = ASC-H) plus high-risk HPV testing were 0.925 and 0.991, and the
      specificities were 0.510 and 0.748, respectively (P < 0.01). Sensitivitives of
      cytology ( > or = LSIL) and cytology (> or = LSIL) plus high risk HPV in
      detecting HSIL were 0.898 and 0.982, respectively, while the specificitives were
      0. 567 and 0.779, respectively (P < 0.01). CONCLUSIONS: The positive rate of high
      risk HPV increases with the gravity of cervical lesions. In patients with
      abnormal cervical cytology, high-risk HPV testing can improve the sensitivity and
      specificity in the screening of HSIL.

PMID- 18051715
TI  - [Inhibition of malignant activities of nasopharyngeal carcinoma cell by ectopic
      expression of BCSC-1 gene].
AB  - OBJECTIVE: To study effects of ectopic expression of BCSC-1 gene on the malignant
      activi-BCSC-1 cDNA was isolated by RT-PCR ties of human nasopharyngeal carcinoma
      cell CNE-2L2. METHODS: and inserted into pMAL-c2X and pcDNA4/myc-His A. BCSC-1
      protein was expressed in prokaryocytes. Rabbit antiserum to BCSC-1 was developed
      by means of immunization of rabbit with the BCSC-1 protein. Expression of BCSC-1
      gene in wild type CNE-2L2 cell (W cell) was examined by real-time RT-PCR and
      immunofluorescence staining with the antiserum as a probe. pcDNA4/myc-His A-BCSC
      1 was transfected into W cell at the presence of LipofectAmine. The cells were
      selected by G418 and cloned. Ectopic expression of BCSC-1 gene in W cell was
      examined by Western blot. Cell growth was detected by drawing of growth curves
      and colony formation tests. Cells were inoculated into nude mice. Size of tumors
      was assayed once a week. Lungs of the mice were sectioned continuously and
      metastatic loci in lungs were examined upon a microscope. RESULTS: Rabbit BCSC-1
      antiserum was prepared. Expression of BCSC-1 gene in W cell was found to be very
      low. CNE-2L2 cell with ectopic expression of BCSC-1 gene was developed. Growth in
      vitro, colony formation, tumorigenesis in nude mice, and lung metastasis of the
      tumor were profoundly inhibited of the cell with ectopic expression of BCSC-1
      gene in comparison with controls, wild type cell and the cell transfected with
      mock. Conclusion Ectopic expression of BCSC-1 gene exerts profound inhibitive
      effect on the malignant activities of CNE-2L2 cell.

PMID- 18051716
TI  - [Identification and expression of non-coding RNAs NC28 and NC119 in human
      tumors].
AB  - OBJECTIVE: To explore and identify the non-coding RNAs related to tumors.
      METHODS: We used RT-PCR and Northern blot to analyze non-coding RNAs in tumor
      tissues and cell lines. RESULTS: Two predicted non-coding RNAs were confirmed to
      be expressed in cancer tissues and cell lines by RT-PCR and DNA sequencing. We
      detected the expression of two non-coding RNA transcripts by Northern blot. The
      length of NC28 was about 1800 nt, and that of NC119 was about 1200nt.
      CONCLUSIONS: NC28 and NC119 have a tumor-associated expression pattern. The non
      coding RNAs may play a role in the development of tumors.

PMID- 18051717
TI  - [Measurement of glutamine concentration in Zelanian rabbits' skeletal muscle by
      non-invasive magnetic resonance spectroscopy].
AB  - OBJECTIVE: To study the feasibility of non-invasive magnetic resonance
      spectroscopy (MRS) in measuring glutamine (GLN) level in Zelanian rabbits'
      skeletal muscle. METHODS: Non-invasive MRS was used to get the data of peak
      height ratio of GLN + glutamic acid (GLx) at 3.8 ppm and creatine (Cr) at 3.0
      ppm, peak area ratio of GLx at 3.8 ppm and Cr at 3.0 ppm. High performance liquid
      chromatography (HPLC) was used to examine the actual GLx levels of muscle from 22
      Zelanian rabbits. The feasibility of MRS was then evaluated by HPLC method.
      RESULTS: The ratio of peak height and peak area of GLx and Cr by means of MRS
      were 0.162 +/- 0.045 and 0.092 +/- 0.065, respectively. The average concentration
      of GLx in skeletal muscle by means of HPLC was (4.19 +/- 2.50) micromol/g. The
      ratio of GLx and plasma Cr level by means of HPLC was 4.576 -/+ 0.599. The ratio
      of peak height and peak area of GLx and Cr by means of MRS were correlated
      significantly with the ratio of concentration of GLx in skeletal muscle and
      plasma Cr by means of HPLC (r = 0.7, P = 0.001; r = 0.6, P = 0.001). CONCLUSION:
      Non-invasive MRS is feasible to measure GLN level in skeletal muscle of rabbit.

PMID- 18051718
TI  - [Experimental siCD44-targeted therapy of human nasopharyngeal carcinoma mediated
      by adenovirus].
AB  - OBJECTIVE: To explore the possibility of treating solid tumor with siCD44.
      METHODS: Human nasopharyngeal carcinoma cell CNE-2L2 with high expression of CD44
      was used in this study. The malignant activities of cells were examined by colony
      formation test, tumorigenesis, and lung metastasis of the tumor in nude mice. Ad5
      siCD44 was constructed and adenoviruses were produced in 293 cells. CNE-2L2 cells
      were subcutaneously inoculated into nude mice. When tumors grew to 50-100 mm3,
      Ad5-siCD44 was injected into tumors, and Ad5-egfp and PBS were also injected as
      controls. The size and weight of tumors were compared after 2 weeks. RESULTS:
      Suppression of CD44 expression profoundly inhibited the malignant activities of
      CNE-2L2 cell. The average sizes of the tumors were (3.139 +/- 0.850), (3.612 +/-
      0.888), and (1.512 +/- 0.742) cm3 after the intra-tumor injection of PBS, Ad5
      egfp, and Ad5-siCD44, respectively, after two weeks. Significant difference was
      found between Ad5-siCD44 group and control groups (P < 0.05). The average weights
      were (2.28 +/- 0.73), (1.83 +/- 0.26), and (1.20 +/- 0.64) g, respectively, and
      significant difference was also found between Ad5-siCD44 group and control groups
      (P < 0.05). CONCLUSION: Intra-tumor injection of Ad5-siCD44 can exhibit the
      therapeutic effect on the tumor inoculated with CNE-2L2 cells with high
      expression of CD44 in nude mice.

PMID- 18051719
TI  - [Effects of interleukin-1beta on nitric oxide production and ATP synthesis in rat
      surplus hepatocytes after partial hepatectomy].
AB  - OBJECTIVE: To detect the nitric oxide (NO) production and energy metabolism of
      the interleukin (IL)-1beta-treated residual hepatocytes from rats after partial
      hepatectomy. METHODS: Forty rats were equally divided into partial hepatectomies
      (PH) group and control group. In the control group the rats were otherwise
      matched and underwent sham surgeries. The residual hepatocytes were separated by
      the collagenase perfusion method. The hepatocytes were cultured with cytokines
      such as IL-1beta. The production of NO in the two groups were measured with
      Griess reagent method, the production of inducible nitric oxide synthase (iNOS)
      protein detected with Western blot, the content of the nucleotide in the
      hepatocytes detected with high-performance liquid chromatography, and the content
      of the ketone body in the hepatocytes of the two groups determined with the
      enzymatic method. Afterwards the ketone body ratio (acetoacetate/beta-hydroxy
      butyrate, KBR) was calculated. RESULTS: The production of NO in the PH group was
      twice as much as that in the Sham group. IL-1beta decreased the content of ATP
      and the KBR in the hepatocytes of both groups, and the decrease magni tude in the
      PH group was significantly larger than that in the Sham group. After the
      injection of L-arginine, the production of NO in the hepatocytes in the PH group
      increased, and the level of ATP and KBR decreased. N(G)-methyl-L-arginine (L
      NMMA), the inhibitor of NO synthase, inhibited the production of NO and reversed
      the decrease of ATP and KBR. CONCLUSION: After partial hepatectomy, increased NO
      production in the hepatocytes after the treatment of interleukin-1beta may
      disturb the function of mitochondria by inhibiting the synthesis of ATP.

PMID- 18051720
TI  - [Hemocompatibility of bovine pericardium with additional sodium bisulfite
      treatment].
AB  - OBJECTIVE: To evaluate the hemocompatibility of glutaraldehyde (GA)-tanned bovine
      pericardium additionally treated by sodium bisulfite (SOB) solution. METHODS: The
      hemocompatibility of GA-tanned bovine pericardium treated by SOB solution is
      evaluated by using dynamic clotting time test, blood platelet adhension test, D
      dimeride determination, and complement activation test. The GA-tanned bovine
      pericardium was used as control. RESULTS: The curve of absorbance-clotting time
      of two kinds of bovine pericardium was similar in dynamic clotting time test.
      There was no significant difference between SOB-treated and control groups in
      blood platelet adhension test. The D-dimeride contents of all bioprostheses were
      at normal level, and the D-dimeride content of GA-tanned bovine pericardium
      treated by SOB solution was significantly lower than that of control group (P <
      0.05). In complement activation test, the level of complement C3a in SOB-treated
      group was significantly lower than that in control group (P < 0.05). CONCLUSION:
      GA-tanned bovine pericardium treated by SOB solution meets the demands of cardiac
      interstitial implanted materials in hemocompatibility.

PMID- 18051721
TI  - [Alterations in gene expression of calcium handling proteins in patients with
      chronic atrial fibrillation].
AB  - OBJECTIVE: To discuss the role of calcium-overloading in initiation and
      maintenance of atrial fibrillation (AF). METHODS: The right atrial appendages
      were obtained from 14 patients with AF and 12 patients with sinus rhythm. The
      mRNA expression of proteins influencing the calcium homeostasis was measured by
      semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and
      normalized to the mRNA level of glyceraldehyde-3- phosphate dehydrogenase. The
      left atrial diameter (LAD), mitral valvular area (MVOA), and systolic pulmonary
      arterial pressure were obtained by echocardiography before surgery. RESULTS:
      Compared to sinus rhythm group, the mRNA levels of L-type calcium channel alc,
      sarcoplasmic reticulum (SR), calcium adenosine triphosphatase (Ca2+ -ATPase), and
      ryanodine receptor type-2 (R(Y) R2) were significantly decreased (P < 0.01); the
      mRNA level of inositol triphosphate receptor type-1 (IP3R1) was significantly
      increased (P < 0.05). No changes in the mRNA expression of phospholamban and
      calsequestrin were observed between two groups (P > 0.05). Correlations were
      found between MVOA and mRNA levels of LVDC-Calc, SR Ca2+ -ATPase (r = 0.719, P =
      0.004; r = 0.625, P = 0.017). The mRNA level of SR Ca2+ -ATPase was negatively
      correlated with LAD (r = -0.573, P = 0.032). CONCLUSIONS: Calcium loading may be
      responsible for the occurrence and maintenance of AF, and abnormal regulation in
      the mRNA expression may be the molecular mechanism of intracellular Ca2+
      overload. The progressive nature of AF involves structural change.

PMID- 18051723
TI  - [Clinical evaluation of hemofiltration without anticoagulation in critically ill
      patients at high risk of bleeding].
AB  - OBJECTIVE: To explore the safety and therapeutic efficacy of hemofiltration
      without anticoagulation in critically ill patients at high risk of bleeding.
      METHODS: We retrospectively analyzed 41 patients undergoing bedside
      hemofiltration in the Intensive Care Unit of PUMC Hospital from December 2005 to
      December 2006. The hemofiltration cases with or without anticoagulation were
      compared. RESULTS: Totally 224 hemofiltration circuits were performed in these 41
      patients, including 114 (50.89%) circuits without anticoagulation in 27 patients
      at high risk of bleeding and 110 (49.11%) with anticoagulation by heparin. The
      circuit life of hemofiltration without anticoagulation was (13.21 +/- 9.73) hours
      (3-55 hours), and that of hemofiltration with anticoagulation was (28. 35 +/-
      26.43) hours (9-126) hours (P < 0.01). The circuit life had no correlation with
      prothrombin time (PT), activitated partial thromboplastin time (APTT), fibrinogen
      (Fbg), and platelet count (PLT) levels before the therapy (P > 0.05). The levels
      of blood creatinine, blood urea nitrogen, potassium, and pH value significantly
      improved after both therapies (P < 0.05). Urea reduction rates were (38.4 +/-
      26.7)% and (24.3 +/- 13.2)% in hemofiltration with and without anticoagulation,
      respectively. The levels of Fbg and PLT significantly decreased after therapy in
      both groups (P < 0.01). PT and APTT did not change in hemofiltration without
      anticoagulation (P > 0.05), while APTIT was prolonged in hemofiltration with
      heparin (P < 0.01). Of the 21 patients who initially received hemofiltration with
      heparin, 7 patients turned to hemofiltration without anticoagulation for
      hemorrhagic complications. Seventeen (41.5%) of 41 patients died during hospital
      stay, but none of them died of complications of hemofiltration. CONCLUSIONS:
      Hemofiltration without anticoagulation reduces bleeding risks and achieves an
      acceptable circuit life. The strategy can be applied as an alternative to
      critically ill patients at high risks of bleeding who need continuous blood
      purification.

PMID- 18051722
TI  - [Biological activity of human single-chain antibody against amyloid beta peptide
      involved in Alzheimer's disease].
AB  - OBJECTIVE: To explore the biological activity of recombinant human single-chain
      antibody against amyloid beta peptide in vitro. METHODS: Human single-chain
      antibody against amyloid beta peptide was obtained from recombinant bacteria. The
      antigen-binding activity of this antibody was measured by enzyme-linked
      immunosorbent assay (ELISA) and competitive ELISA. Human neuroblastoma SH-SY5Y
      cells were used as cell models to test the protective role of human single-chain
      antibody against amyloid beta peptide. RESULTS: Recombinant human single-chain
      antibody was mainly located in the insoluble inclusion bodies of bacteria. The
      antibody was dissolved by urea and purified by metal affinity chromatography as
      active form to bind synthetic amyloid beta peptide 40 or amyloid beta peptide 42.
      The improvement of the survival rates of human neuroblastoma cells was
      significantly superior in amyloid peptide 42 plus equimolar antibody group than
      in amyloid peptide 42 group (P < 0.05), and was significantly superior in the
      amyloid peptide 40 plus equimolar antibody group than in amyloid peptide 40 group
      (P < 0.01). CONCLUSION: The recombinant human single-chain antibody against beta
      amyloid peptide 40 from E. coli can partially inhibit the neurotoxicity effect of
      amyloid beta peptide in vitro.

PMID- 18051724
TI  - [Hemodynamic responses to orotracheal intubation with upsherscope or Macintosh
      direct laryngoscope].
AB  - OBJECTIVE: To compare the hemodynamic responses to orotracheal intubation via
      Upsher-scope (USSP) or Macintosh direct laryngoscope (MDLS) under general
      anesthesia. METHODS: Fifty patients with ASA grade I-II and undergoing the
      elective plastic surgery and requiring orotracheal intubation were randomly
      allocated to either the USSP (U group) (n=25) or MDLS (M group) (n=25). After
      standard intravenous anesthetic induction, orotracheal intubation was performed
      using a USSP or a MDLS. Noninvasive systolic blood pressure (SBP), diastolic
      blood pressure (DBP), and heart rate (HR) were recorded before and after
      anesthetic induction, at intubation and every minute thereafter for 5 minutes.
      The time spent in tracheal intubation was recorded. The mean blood pressure (MBP)
      and rate-pressure product (RPP) were calculated. RESULTS: The intubation time was
      not significantly different between these two groups (P > 0.05). After anesthetic
      induction, SBP, DBP, MAP, and RPP in these two groups decreased significantly as
      compared with preinduction values. The orotracheal intubation caused significant
      increases in SBP, DBP, MAP, and RPP in these two groups in comparision with
      postinduction values (P < 0.05), but these hemodynamic changes lasted only 1 to 2
      minutes and then decreased gradually to the postinduction level. The blood
      pressure changes caused by orotracheal intubation did not exceed the preinduction
      values (P > 0.05). As compared to, the maximal HR values in these two groups
      during observation (from the beginning of intravenous anesthetic induction to 5
      min after intubation) were significantly higher than their preinduction values (P
      < 0.05). The maximal RPP values in M group during observation were significantly
      higher than their preinduction values (P < 0.05), but no such significant
      difference was observed in U group (P > 0.05). The hemodynamic data at each time
      point during the observation had no significant differences between these two
      groups. (P > 0.05). CONCLUSIONS: Orotracheal intubation using the USSP and MDLS
      may result in similar hemodynamic responses. The standard general anaesthesia can
      effectively inhibit the pressor, but not the tachycardiac responses caused by
      orotracheal intubation via USSP or MDLS. USSP is not superior than MDLS in
      palliating the adverse cardiovascular stress responses to orotracheal intubation.

PMID- 18051725
TI  - [Risk factors in the living environment of early spontaneous abortion pregnant
      women].
AB  - OBJECTIVE: To study the relationship between early spontaneous abortion and
      living environment, and explore the risk factors of spontaneous abortion.
      METHODS: We conducted analysis based on the interview of 200 spontaneous abortion
      cases and the matched control (age +/- 2 years) by using multifactor Logistic
      regression analysis. RESULTS: The proportions of watching TV > or =10 hours/week,
      operating computer > or =45 hours/week, using copycat, microwave oven and mobile
      phone, electromagnetism equipment near the dwell or work place, e. g. switch room
      < or =50 m and launching tower < or =500 m in the cases are significantly higher
      than those in the controls in single factor analysis (all P < 0.05). After
      adjusted the effect of other risk factors by multifactor analysis, using
      microwave oven and mobile phone, contacting abnormal smell of fitment material >
      or =3 months, having emotional stress during the first term of pregnancy and
      spontaneous abortion history were significantly associated with risk of
      spontaneous abortion. The odds ratios of these risk factors were 2.23 and 4.63,
      respectively. CONCLUSION: Using microwave oven and mobile phone, contacting
      abnormal smell of fitment material > or =3 months, having emotional stress during
      the first term of pregnancy, and spontaneous abortion history are risk factors of
      early spontaneous abortion.

PMID- 18051726
TI  - [Etiological diagnosis and specific treatment of chronic cough in 106 patients].
AB  - OBJECTIVE: To analyze the etiological diagnosis and efficacy of specific therapy
      of chronic cough. METHODS: Totally 106 patients with chronic cough were diagnosed
      using a diagnostic protocol based on the Guideline on Diagnosis and Treatment of
      Chronic Cough established by China Medical Association, which included history
      inquiry, physical examination, pulmonary function tests, X-ray or CT of paranasal
      sinuses or chest, 24-hour esophageal pH monitoring, and sputum cell
      differentials. The etiological diagnosis was made according to clinical
      manifestations, examination results, and response to specific therapy. RESULTS:
      The cause of chronic cough was confirmed in 101 patients (95.3%). Cough due to a
      single cause was found in 81 patients (80.2%), and due to multiple causes in 20
      patients (19.8%). The causes included cough variant asthma (CVA) in 66 patients
      (62.3%), postnasal drip syndrome (PNDs) in 15 patients (14.1%), gastroesophageal
      reflux (GERC) in 11 patients (10.4%), post-infection cough (PIC) in 4 patients
      (3.8%), angiotensin converting enzyme inhibitor (ACEI) induction in 3 patients
      (2.8%), and eosinophilic bronchitis (EB) in 2 patients (1.9%). Five patients
      (4.7%) had not been definitely diagnosed. After specific therapy based on
      diagnosis, cough disappeared in 92 patients (91.1%) and alleviated in 9 patients
      (8.9%). CONCLUSIONS: CVA, PNDs, and GERC are the most common causes of chronic
      cough. Specific therapy based on definite cause can result in good outcome.

PMID- 18051727
TI  - [Current advances in the mechanic studies of human papillomavirus-induced
      oncogenesis].
AB  - Human papillomavirus (HPV) is a common small DNA tumor virus that specifically
      infects squamous epithelial cells and causes benign or malignant epithelial
      lesions such as genital warts and cervical cancer. High-risk HPV is detected in
      specimens of more than 90% of cervical cancer. In the 7. 9 kb genome of HPV, E6
      and E7 are the crucial viral oncoproteins that consistently maintained after
      viral integration into host cell genome. These two proteins interfere with cell
      proliferation and differentiation through interacting with important tumor
      suppressors including p53 and pRb. High-risk HPV E6/E7 also induces genomic
      instability, facilitating cell transformation.

PMID- 18051728
TI  - [Human papillomavirus types and their related diseases].
AB  - With the development of biomolecular technology, more human papillomavirus (HPV)
      types have been found to be related with various diseases. High-risk HPV 16, 18,
      31, 33, 45, 52, and 61 have shown causal relationship with cancers of the cervix,
      vulva, vagina, penis, anus, oral cavity, and oropharynx. Low-risk HPV 6 and 11
      have shown causal relationship with genital warts. HPV may also cause cancer of
      the larynx. However, the relationships between HPV and esophagus and lung cancers
      are still controversial.

PMID- 18051729
TI  - [Advances in human papillomavirus therapeutic vaccine].
AB  - Human papillomavirus (HPV) infection is very common but with limited therapies
      available. Although the prophylactic vaccination will be promoted worldwide soon,
      it can only show its benefits decades later. For individuals who already have
      established infections and dysplasias, it has little efficacy. In contrast, the
      therapeutic vaccines bridge the temporal deficit by fighting against the
      established HPV infections and HPV-related diseases. HPV oncogenes may be
      delivered in viral and bacterial vectors, in peptides or protein, in nucleic acid
      form, or in cell-based vaccines. This review summarizes the clinical trials of
      HPV therapeutic vaccines under the way and the different preclinical research
      strategies that are under investigations.

PMID- 18051730
TI  - [Role of high-risk human papillomavirus testing in the screening and management
      of cervical cancer precursors].
AB  - Human papillomavirus (HPV) infection is an essential cause of cervical cancer.
      HPV testing therefore may maximize the clinical benefits of cervical screening
      and abnormal cervical cytology management. A negative HPV test in combination
      with a normal Pap test result in women age 30 years or older allows the safe
      extension of the cervical screening interval to 3 years. However, because HPV
      infection is common in young women and is usually transient, HPV testing is not
      recommended as part of primary cervical screening for women younger than 30
      years. HPV testing is recommended for women of any age as a triage test with
      atypical squamous cells of undetermined significance (ASC-US) results and as an
      option for follow-up of women with HPV-positive ASC-US, atypical squamous cells
      "cannot rule out high-grade", low-grade squamous intraepithelial lesions, or
      atypical granular cells not found to have CIN 2/3. HPV testing is also
      recommended as an alternative to colposcopy and/or cytology for follow-up of
      treated cases. Proper use of HPV testing improves the management of women with
      cytologic abnormalities.

PMID- 18051731
TI  - Measuring obesity to assess cardiovascular risk--inch tape, weighing machine, or
      both?

PMID- 18051732
TI  - Body-mass index, waist-size, waist-hip ratio and cardiovascular risk factors in
      urban subejcts.
AB  - BACKGROUND AND OBJECTIVE: Influence of obesity as determinant of cardiovascular
      risk factors has not been well studied. To determine association of obesity,
      measured by body-mass index (BMI), waist-size or waist-hip ratio (WHR), with
      multiple risk factors in an urban Indian population we performed an
      epidemiological study. METHODS: Randomly selected adults > or = 20 years were
      studied using stratified sampling. Target sample was 1800 (men 960, women 840).
      1123 subjects (response 62.4%) were evaluated and blood samples were available in
      532 men and 559 women (n=1091, response 60.6%). Measurement of anthropometric
      variables, blood pressure, fasting blood glucose and lipids was performed.
      Atherosclerosis risk factors were determined using current guidelines. Pearson's
      correlation coefficients (r) of BMI, waist and WHR with various risk factors were
      determined. BMI was categorized into five groups: <20.0 Kg/m2, 20.0-22.9, 23.0
      24.9, 25.0-29.9, and > or = 30 Kg/m2; waist size was divided into five groups and
      WHR into six groups in both men and women. Prevalence of cardiovascular risk
      factors, smoking, hypertension, diabetes, metabolic syndrome and dyslipidaemias
      was determined in each group and trends analyzed using least-squares regression.
      RESULTS: There is a significant positive correlation of BMI, waist-size and WHR
      with systolic BP (r= 0.46 to 0.13), diastolic BP (0.42 to 0.16), fasting glucose
      (0.15 to 0.26), and LDL cholesterol (0.16 to 0.03) and negative correlation with
      physical activity and HDL cholesterol (-0.22 to -0.08) in both men and women
      (p<0.01). With increasing BMI, waist-size and WHR, prevalence of hypertension,
      diabetes, and metabolic syndrome increased significantly (p for trend <0.05). WHR
      increase also correlated significantly with prevalence of high total and LDL
      cholesterol and triglycerides (p <0.05). CONCLUSIONS: There is a continuous
      positive relationship of all markers of obesity (body-mass index, waist size and
      waist hip ratio) with major coronary risk factors- hypertension, diabetes and
      metabolic syndrome while WHR also correlates with lipid abnormalities.

PMID- 18051733
TI  - Role of simple needle aspiration in the management of spontaneous pneumothorax.
AB  - OBJECTIVE: To determine the efficacy of simple needle aspiration in the
      management of primary spontaneous pneumothorax. Not all patients with
      pneumothorax require intercostal tube drainage (ICTD). Some patients can be
      managed conservatively by simple needle aspiration of air from pleural space. It
      is a cheap and easy alternative to ICTD which can be done on out patient basis.
      MATERIALS AND METHODS: All patients of spontaneous pneumothorax presenting for
      the first time were included in this study, after obtaining baseline
      investigations like chest X-ray, ECG, serum creatinine, blood sugar etc. They
      were managed by ICTD or simple needle aspiration. Chest X-ray was done 6 hours
      after the procedure (ICTD), 24 hours after aspiration and prior to ICTD removal
      or before hospital discharge. Patients who had undergone simple needle aspiration
      were allowed to go home following a few hours of observation after explaining the
      warning symptoms and the need for reevaluation after 24 hrs, if prompt follow-up
      could be ensured otherwise they were admitted along with patients undergoing
      ICTD. RESULTS: Eighty two patients of spontaneous pneumothorax were included in
      this study during a-period of 12 months (May- 04 to April - 05). Out of these 40
      (49%) patients were managed by ICTD, 42 (51%) patients were subjected to simple
      needle aspiration. Thirty two (76%) patients responded to simple needle
      aspiration while the remaining 10 patients required ICTD finally. There were no
      complications in the patients managed by simple needle aspiration; they had less
      chest pain and lesser duration of hospital stay. CONCLUSION: Spontaneous
      pneumothorax may be managed by simple needle air aspiration primarily, unless
      contraindicated (tension pneumothorax), or in patients requiring mechanical
      ventilation. For symptomatic patient it is the recommended procedure.

PMID- 18051734
TI  - Glycemic level at the first visit and prediction of GDM.
AB  - OBJECTIVE: To evaluate the glycemic level at the first visit that is likely to
      predict gestational diabetes mellitus (GDM). METHODS: Consecutive pregnant women
      underwent a 75g oral glucose tolerance Test (OGTT) recommended by WHO and
      diagnosed GDM if 2hr post plasma glucose (PG) value > or = 140 mg/dl. Women with
      normal OGTT results at the first visit were screened again with an OGTT at the
      subsequent visits. RESULTS: A total of 4151 pregnant women from different
      trimesters underwent OGTT. Of them 739 women (17.8%) had GDM. Among the GDM
      women, 528 (71.4%) were detected at the first visit. On screening during
      subsequent visits, GDM was diagnosed in the remaining 211(28.6%) women who had
      normal OGTT in the first visit. We performed the analysis taking the glycemic
      level in the first visit of 211 pregnant women who manifested GDM in the
      subsequent visit. During normal pregnancy, 2hr PG level is < 120 mg/dl. Taking
      this value into consideration among the 211 women who turned to have GDM in the
      subsequent visits 119 women (56.4%) had 2hrPG > or = 120 mg/dl and the remaining
      92(43.6%) had 2hrPG < 120 mg/dl. CONCLUSION: Pregnant women irrespective of 2 hr
      PG > or = or < 120 mg/dl at initial visit progressed to GDM in the subsequent
      visit. No glycemic level in the early weeks of pregnancy predicts GDM and at the
      same time at no statistically significant glycemic cut-off level could we say
      that a woman will not develop GDM. Hence rescreening in the subsequent trimester
      or visits is essential.

PMID- 18051735
TI  - A man with multiple membrane calcification: flurosis.

PMID- 18051736
TI  - A case with discrete atherosclerotic aneursyms of all coronary vessels.

PMID- 18051737
TI  - Medical treatment of ulcerative colitis.
AB  - Ulcerative colitis is an inflammatory bowel disease of uncertain etiology with
      recurrent symptoms and considerable morbidity. There is no known medical cure for
      ulcerative colitis. The ultimate goal of treatment in any patient suffering from
      ulcerative colitis is inducing and maintaining clinical remission. New uses are
      being found for old drugs, and more and more new drugs are becoming available.
      This article is not only intended to help clinicians to evaluate new treatments
      for ulcerative colitis, but also to revisit older treatments with a critical eye.

PMID- 18051738
TI  - Causation, prevention and reversal of vascular endothelial dysfunction.
AB  - Insulin Resistance along with endothelial dysfunction give rise to a
      constellation of syndromes designated as IRS/MBS metabolic syndrome. Endothelial
      dysfunction starts early in life much before the development of structural
      atherosclerosis. Recent insights into vascular biology enable us to understand
      the molecular mechanisms underlying endothelial dysfunction, and the scope and
      need for prevention of "pre-clinical" coronary atherosclerosis through lifestyle
      modification; diet, exercise and stress management. Diminished production of
      nitric oxide (NO) and/or increased inactivation of NO through oxidative stress
      (reactive oxygen species ROS and reactive nitrogen species (RNS) are the basis of
      endothelial dysfunction hence increasing the bioavailability of NO and decreasing
      its inactivation is the aim of prevention and reversal of endothelial
      dysfunction. Insulin regulates constitutive NOS gene expression in endothelial
      cells in vivo; vasodilation is an important component of Insulin-stimulated whole
      body glucose uptake. Successful strategies are: PPAR alpha and gamma agonists
      which increase NO production in endothelium; anti-oxidants such as vit. E and C;
      supplementation with L-arginine, tetrahydrobiopterin-BH4 or sepiapterin
      (precursor of BH4), SOD mimetic tempol, statins which apart from lowering
      cholesterol improve NO production, selective beta1 adrenoreceptor antagonists
      such as nebivolol; suppression of angiotensin-mediated endothelin production by
      ACE inhibitors and ATR blockers; CB1 receptor blockers, PKCb inhibitors, nitric
      oxide donors (glyceryl trinitrate and isosorbide dinitrate), dietary supplements
      of EPA/DHA and regular physical exercise and control of mental stress.

PMID- 18051739
TI  - Granulomatous hypophysitis--an interesting and rare cause mimicking pituitary
      mass.
AB  - Idiopathic granulomatous hypophysitis is a rare entity. The usual clinical
      presentation is that of an expanding mass lesion with varying degree of
      hypopituitarism. This patient described presented to us with severe headache
      along with panhypopituitarism and post-operative diabetes insipidus.

PMID- 18051740
TI  - Cerebrotendinous xanthomatosis: a treatable cause of metabolic ataxia.
AB  - Cerebrotendinous xanthomatosis is an exceptionally rare condition in Indian
      subcontinent, however, it is potentially treatable if diagnosed. We present and
      discuss the clinical presentation and investigations in a case of
      cerebrotendinous xanthomatosis (CTX).

PMID- 18051741
TI  - Barium poisoning mimicking Guillain-Barre syndrome.
AB  - Barium poisoning is an important cause of areflexic quadriplegia associated with
      hypokalemia. Presenting features may mimic Guillain-Barre syndrome. A high index
      of suspicion of barium poisoning in two patients who presented with features
      resembling Guillain-Barre syndrome, led to timely management and early recovery
      in both the cases.

PMID- 18051742
TI  - Medical philately. Sir Arthur Conan Doyle (1859-1930).

PMID- 18051743
TI  - Bilateral superior cerebellar artery infarcts: unusual presentation in two
      patients of stroke in young.
AB  - Stroke or cerebrovascular disease is one of the most important causes of high
      morbidity and mortality throughout the world. Stroke in young individuals poses a
      major problem as these individuals are bread earners of the family. Ischaemic
      strokes are increasingly being attributed to causes other than atherothrombotic
      disease. Disorders of coagulation leading to thrombotic disorders are relatively
      uncommon conditions which are implicated in approximately 1% of all ischaemic
      strokes and 4-8% of young strokes. Bilateral superior cerebellar infarcts due to
      hypercoagulable state are extremely rare situations. Here we present two patients
      with unusual presentation of stroke in young due to hypercoagulable state.

PMID- 18051744
TI  - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) and
      neurological crisis due to acute intermittent porphyria, successfully treated
      with haemodialysis.
AB  - We report an eighteen year old female, a case of acute intermittent porphyria
      with syndrome of inappropriate antidiuretic hormone secretion, as presenting
      feature for its rarity. The neurological crisis was successfully treated with
      haemodialysis.

PMID- 18051745
TI  - Gujjar lung.

PMID- 18051746
TI  - Health professionals' characteristics associated with requisitioning
      electroencephalography in breath holding spells.

PMID- 18051747
TI  - Cardiogenic unilateral pulmonary edema.

PMID- 18051748
TI  - Nitrogen control in Corynebacterium glutamicum: proteins, mechanisms, signals.
AB  - In order to utilize different nitrogen sources and to survive in a situation of
      nitrogen limitation, microorganisms have developed sophisticated mechanisms to
      adapt their metabolism to a changing nitrogen supply. In this communication, the
      recent knowledge of nitrogen regulation in the amino acid producer
      Corynebacterium glutamicum is summarized. The core adaptations of C. glutamicum
      to nitrogen limitation on the level of transcription are controlled by the global
      regulator AmtR. Further components of the signal pathway are GlnK, a P(II)-type
      signal transduction protein, and GlnD. Mechanisms involved in nitrogen control in
      C. glutamicum regulating gene expression and protein activity are repression of
      transcription, protein-complex formation, protein modification by adenylylation,
      change of intracellular localization, and proteolysis.

PMID- 18051749
TI  - Effect of culture conditions on canthaxanthin production by Dietzia
      natronolimnaea HS-1.
AB  - This study investigated the effects of various culture parameters (carbon
      sources, temperature, initial pH of culture, NaCl concentration, and light) on
      the growth and canthaxanthin production by Dietzia natronolimnaea HS-1. The
      results showed that the most effective carbon source for growth and canthaxantin
      production was glucose, and the best pH and temperature were 7 and 31 degrees C,
      respectively. In addition, the biomass and canthaxanthin production increased in
      a medium without NaCl and in the presence of light. Under the optimized
      conditions, the maximum biomass, total carotenoid, and canthaxanthin production
      were 6.12 +/- 0.21 g/l, 4.51 +/- 0.20 mg/l, and 4.28 +/- 0.15 mg/l, respectively,
      in an Erlenmeyer flask system, yet increased to 7.25 g/l, 5.48 mg/l, and 5.29
      mg/l, respectively, in a batch fermenter system.

PMID- 18051750
TI  - Morphology and adhesion of Campylobacter jejuni to chicken skin under varying
      conditions.
AB  - The adhesion of Campylobacter jejuni to chicken skin, along with the associated
      morphological changes under aerobic conditions at 4, 25, and 37 degrees C and
      microaerobic (O2 5%, CO2 10%, N2 85%) conditions, were investigated using
      confocal laser scanning microscopy (CLSM), flow cytometry, and plate counting.
      The morphological change of C. jejuni from a spiral shape to a coccoid form or
      VBNC form (viable but nonculturable form) progressed rapidly under aerobic
      conditions at 25, 37, and 4 degrees C. As regards adhesion, the C. jejuni cells
      were mostly located in the crevices and feather follicles of the chicken skin,
      where the cells in the feather follicles floated freely in the entrapped water,
      even after the skin was rinsed quite thoroughly. CLSM also revealed the
      penetration of some spiral-shaped C. jejuni cells into the chicken skin. Even
      after changing their shape at various temperatures, coccoid-form C. jejuni cells
      were still found in the crevices and feather follicles of the chicken skin.

PMID- 18051751
TI  - Comparative proteomic analyses of the yeast Saccharomyces cerevisiae KNU5377
      strain against menadione-induced oxidative stress.
AB  - The Saccharomyces cerevisiae KNU5377 strain, which was isolated from spoilage in
      nature, has the ability to convert biomass to alcohol at high temperatures and it
      can resist against various stresses. In order to understand the defense
      mechanisms of the KNU5377 strain under menadione (MD) as oxidative stress, we
      used several techniques for study: peptide mass fingerprinting (PMF) by matrix
      assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry
      (MS) followed by two-dimensional (2D) gel electrophoresis, liquid chromatography
      electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), and surface
      enhanced laser desorption ionization-time of flight (SELDI-TOF) technology. Among
      the 35 proteins identified by MALDI-TOF MS, 19 proteins including Sod1p, Sod2p,
      Tsa1p, and Ahp1p were induced under stress condition, while 16 proteins were
      augmented under normal condition. In particular, five proteins, Sod1p, Sod2p,
      Ahp1p, Rib3p, Yaf9p, and Mnt1p, were induced in only stressed cells. By LC-ESI
      MS/MS analysis, 37 proteins were identified in normal cells and 49 proteins were
      confirmed in the stressed cells. Among the identified proteins, 32 proteins were
      found in both cells. Five proteins including Ye1047cp and Met6p were only
      upregulated in the normal cells, whereas 17 proteins including Abp1p and Sam1p
      were elevated in the stressed cells. It was interesting that highly hypothetical
      proteins such as Ynl281wp, Ygr279cp, Ypl273wp, Ykl133cp, and Ykr074wp were only
      expressed in the stressed cells. SELDI-TOF analysis using the SAX2 and WCX2 chips
      showed that highly multiple-specific protein patterns were reproducibly detected
      in ranges from 2.9 to 27.0 kDa both under normal and stress conditions.
      Therefore, induction of antioxidant proteins, hypothetical proteins, and low
      molecular weight proteins were revealed by different proteomic techniques. These
      results suggest that comparative analyses using proteomics might contribute to
      elucidate the defense mechanisms of KNU5377 under MD stress.

PMID- 18051752
TI  - Metabolic characterization of lactic acid bacterium Lactococcus garvieae sk11,
      capable of reducing ferric iron, nitrate, and fumarate.
AB  - A lactic acid bacterium capable of anaerobic respiration was isolated from soil
      with ferric iron-containing glucose basal medium and identified as L. garvieae by
      using 16S rDNA sequence homology. The isolate reduced ferric iron, nitrate, and
      fumarate to ferrous iron, nitrite, and succinate, respectively, under anaerobic
      N2 atmosphere. Growth of the isolate was increased about 30-39% in glucose basal
      medium containing nitrate and fumarate, but not in the medium containing ferric
      iron. Specifically, metabolic reduction of nitrate and fumarate is thought to be
      controlled by the specific genes fnr, encoding FNR-like protein, and nir,
      regulating fumarate-nitrate reductase. Reduction activity of ferric iron by the
      isolate was estimated physiologically, enzymologically, and electrochemically.
      The results obtained led us to propose that the isolate metabolized nitrate and
      fumarate as an electron acceptor and has specific enzymes capable of reducing
      ferric iron in coupling with anaerobic respiration.

PMID- 18051753
TI  - Production of acyl-homoserine lactone quorum-sensing signals is widespread in
      gram-negative Methylobacterium.
AB  - Members of Methylobacterium, referred as pink-pigmented facultative
      methylotrophic bacteria, are frequently associated with terrestrial and aquatic
      plants, tending to form aggregates on the phyllosphere. We report here that the
      production of autoinducer molecules involved in the cell-to-cell signaling
      process, which is known as quorum sensing, is common among Methylobacterium
      species. Several strains of Methylobacterium were tested for their ability to
      produce N-acyl-homoserine lactone (AHL) signal molecules using different
      indicators. Most strains of Methylobacterium tested could elicit a positive
      response in Agrobacterium tumefaciens harboring lacZ fused to a gene that is
      regulated by autoinduction. The synthesis of these compounds was cell-density
      dependent, and the maximal activity was reached during the late exponential to
      stationary phases. The bacterial extracts were separated by thin-layer
      chromatography and bioassayed with A. tumefaciens NT1 (traR, tra::lacZ749). They
      revealed the production of various patterns of the signal molecules, which are
      strain dependent. At least two signal molecules could be detected in most of the
      strains tested, and comparison of their relative mobilities suggested that they
      are homologs of N-octanoyl-DL-homoserine lactone (C8-HSL) and N-decanoyl-DL
      homoserine lactone (C10-HSL).

PMID- 18051754
TI  - IVET-based identification of virulence factors in Vibrio vulnificus MO6-24/O.
AB  - Vibrio vulnificus is an opportunistic pathogen that causes septicemia in humans.
      To identify the genes associated with its pathogenicity, in vivo expression
      technology (IVET) was used to select genes specifically expressed in a host, yet
      not significantly in vitro. Random lacZ-fusions in the genome of V. vulnificus
      strain MO6-24/O were constructed using an IVET vector, pSG3, which is a suicide
      vector containing promoterless-aph and -lacZ as reporter genes. A total of
      approximately 18,000 resulting library clones were then intraperitoneally
      injected into BALB/c mice using a colony forming unit (CFU) of 1.6 x 10(6). Two
      hours after infection, kanamycin was administered at 200 microg per gram of mouse
      weight. After two selection cycles, 11 genes were eventually isolated, which were
      expressed only in the host. Among these genes, VV20781 and VV21007 exhibiting a
      homology to a hemagglutinin gene and tolC, respectively, were selected based on
      having the highest frequency. When compared to wild-type cells, mutants with
      lesions in these genes showed no difference in the rate of growth rate, yet a
      significant decrease in cytotoxicity and the capability to form a biofilm.

PMID- 18051755
TI  - Transcriptome analysis of phosphate starvation response in Escherichia coli.
AB  - Escherichia coli has a PhoR-PhoB two-component regulatory system to detect and
      respond to the changes of environmental phosphate concentration. For the E. coli
      W3110 strain growing under phosphate-limiting condition, the changes of global
      gene expression levels were investigated by using DNA microarray analysis. The
      expression levels of some genes that are involved in phosphate metabolism were
      increased as phosphate became limited, whereas those of the genes involved in
      ribosomal protein or amino acid metabolism were decreased, owing to the
      stationary phase response. The upregulated genes could be divided into
      temporarily and permanently inducible genes by phosphate starvation. At the peak
      point showing the highest expression levels of the phoB and phoR genes under
      phosphate-limiting condition, the phoB- and/or phoR-dependent regulatory
      mechanisms were investigated in detail by comparing the gene expression levels
      among the wild-type and phoB and/or phoR mutant strains. Overall, the phoB
      mutation was epistatic over the phoR mutation. It was found that PhoBR and PhoB
      were responsible for the upregulation of the phosphonate or glycerol phosphate
      metabolism and high-affinity phosphate transport system, respectively. These
      results show the complex regulation by the PhoR-PhoB two-component regulatory
      system in E. coli.

PMID- 18051756
TI  - Molecular and ecological analyses of microbial community structures in biofilms
      of a full-scale Aerated Up-Flow Biobead process.
AB  - Molecular and cultivation techniques were used to characterize the bacterial
      communities of biobead reactor biofilms in a sewage treatment plant to which an
      Aerated Up-Flow Biobead process was applied. With this biobead process, the
      monthly average values of various chemical parameters in the effluent were
      generally kept under the regulation limits of the effluent quality of the sewage
      treatment plant during the operation period. Most probable number (MPN) analysis
      revealed that the population of denitrifying bacteria was abundant in the biobead
      #1 reactor, denitrifying and nitrifying bacteria coexisted in the biobead #2
      reactor, and nitrifying bacteria prevailed over denitrifying bacteria in the
      biobead #3 reactor. The results of the MPN test suggested that the biobead #2
      reactor was a transition zone leading to acclimated nitrifying biofilms in the
      biobead #3 reactor. Phylogenetic analysis of 16S rDNA sequences cloned from
      biofilms showed that the biobead #1 reactor, which received a high organic
      loading rate, had much diverse microorganisms, whereas the biobead #2 and #3
      reactors were dominated by the members of Proteobacteria. DGGE analysis with the
      ammonia monooxygenase (amoA) gene supported the observation from the MPN test
      that the biofilms of September were fully developed and specialized for
      nitrification in the biobead reactor #3. All of the DNA sequences of the amoA
      DGGE bands were very similar to the sequence of the amoA gene of Nitrosomonas
      species, the presence of which is typical in the biological aerated filters. The
      results of this study showed that organic and inorganic nutrients were
      efficiently removed by both denitrifying microbial populations in the anaerobic
      tank and heterotrophic and nitrifying bacterial biofilms well-formed in the three
      functional biobead reactors in the Aerated Up-Flow Biobead process.

PMID- 18051757
TI  - Detection and characterization of a lytic Pediococcus bacteriophage from the
      fermenting cucumber brine.
AB  - Of the twelve lytic bacteriophages recovered from five different fermenting
      cucumber tanks that were inoculated with Pediococcus sp. LA0281, a lytic phage,
      phips05, was characterized in the present study. The plaques were mostly clear
      and round-shaped on the lawn of starter strain, indicating lytic phage. Overall
      appearance indicated that it belongs to the Siphoviridae family or Bradley's
      group B1, with a small isometric head and a flexible noncontractile tail with
      swollen base plate. The average size was found to be 51.2 nm in head diameter and
      11.6 nm wide x 129.6 nm long for the tail. The single-step growth kinetics curve
      showed that the eclipse and the latent period were 29 min and 34 min,
      respectively, and an average burst size was calculated to be 12 particles per
      infective center. The optimum proliferating temperature (35 degrees C) was
      slightly lower than that of cell growth (35 to 40 degrees C). The structural
      proteins revealed by SDS-PAGE consisted of one main protein of 33 kDa and three
      minor proteins of 85, 58, and 52 kDa. The phage genome was a linear double
      stranded DNA without cohesive ends. Based on the single and double digestion
      patterns obtained by EcoRI, HindIII, and SalI, the physical map was constructed.
      The overall size of the phage genome was estimated to be 24.1 kb. The present
      report describes the presence of a lytic phage active against a commercial
      starter culture Pediococcus sp. LA0281 in cucumber fermentation, and a
      preliminary study characterizes the phage on bacterial successions in the process
      of starter-added cucumber fermentation.

PMID- 18051758
TI  - Black rice (Oryza sativa L. var. japonica) hydrolyzed peptides induce expression
      of hyaluronan synthase 2 gene in HaCaT keratinocytes.
AB  - Black rice (Oryza sativa L. var. japonica) has been used in folk medicine in
      Asia. To understand the effects of black rice hydrolyzed peptides (BRP) from
      germinated black rice, we assessed the expression levels of about 20,000
      transcripts in BRP-treated HaCaT keratinocytes using human 1A oligo microarray
      analysis. As a result, the BRP treatment showed a differential expression ratio
      of more than 2-fold: 745 were activated and 1,011 were repressed. One of the most
      interesting findings was a 2-fold increase in hyaluronan synthase 2 (HAS2) gene
      expression by BRP. Semiquantitative RT-PCR showed that BRP increased HAS2 mRNA in
      dose-dependent manners. ELISA showed that BRP effectively increased hyaluronan
      (HA) production in HaCaT keratinocytes.

PMID- 18051759
TI  - A two-strain mixture of rhizobacteria elicits induction of systemic resistance
      against Pseudomonas syringae and Cucumber mosaic virus coupled to promotion of
      plant growth on Arabidopsis thaliana.
AB  - We evaluated a commercial biopreparation of plant growth-promoting rhizobacteria
      (PGPR) strains Bacillus subtilis GB03 and B. amyloliquefaciens IN937a formulated
      with the carrier chitosan (BioYield) for its capacity to elicit growth promotion
      and induced systemic resistance against infection by Cucumber Mosaic Virus (CMV)
      and Pseudomonas syringae pv. tomato DC3000 in Arabidopsis thaliana. The
      biopreparation promoted plant growth of Arabidopsis hormonal mutants, which
      included auxin, gibberellic acid, ethylene, jasmonate, salicylic acid, and
      brassinosteroid insensitive lines as well as each wild-type. The biopreparation
      protected plants against CMV based on disease severity in wild-type plants.
      However, virus titre was not lower in control plants and those treated with
      biopreparation, suggesting that the biopreparation induced tolerance rather than
      resistance against CMV. Interestingly, the biopreparation induced resistance
      against CMV in NahG plants, as evidenced by both reduced disease severity and
      virus titer. The biopreparation also elicited induced resistance against P.
      syringae pv. tomato in the wild-type but not in NahG transgenic plants, which
      degrade endogenous salicylic acid, indicating the involvement of salicylic acid
      signaling. Our results indicate that some PGPR strains can elicit plant growth
      promotion by mechanisms that are different from known hormonal signaling
      pathways. In addition, the mechanism for elicitation of induced resistance by
      PGPR may be pathogen-dependent. Collectively, the two-Bacilli strain mixture can
      be utilized as a biological inoculant for both protection of plant against
      bacterial and viral pathogens and enhancement of plant growth.

PMID- 18051760
TI  - Characterization of paraplantaricin C7, a novel bacteriocin produced by
      Lactobacillus paraplantarum C7 isolated from kimchi.
AB  - A Lactobacillus paraplantarum strain producing a bacteriocin was isolated from
      kimchi using the spot-on-the lawn method and named L. paraplantarum C7. The
      bacteriocin, paraplantaricin C7, was found to inhibit certain Lactobacillus
      strains, including L. plantarum, L. pentosus, and L. delbrueckii subsp. lactis.
      It also inhibited Enterococcus faecalis, yet did not inhibit most of the other
      LAB (lactic acid bacteria) tested. The maximum level of paraplantaricin C7
      activity was observed under the culture conditions of 25 degrees C and a constant
      pH of 4.5. Paraplantaricin C7 retained 90% of its activity after 10 min of
      treatment at 100 degrees C and remained stable within a pH range of 2-8. Based on
      a culture supernatant, paraplantaricin C7 was purified by DEAE-Sephacel column
      chromatography and C18 reverse-phase HPLC. SDS-PAGE and activity staining were
      then conducted using the purified paraplantaricin C7, and its molecular mass
      determined to be about 3,800 Da. The 28 N-terminal amino acids from the purified
      paraplantaricin C7 were determined, and the structural gene encoding
      paraplantaricin C7, ppnC7, was cloned by PCR using degenerate primers based on
      the N-terminal amino acid sequence. The nucleotide sequences for ppnC7 and other
      neighboring orfs exhibited a limited homology to the previously reported
      plantaricin operon genes. Paraplantaricin C7 is a novel type II bacteriocin
      containing a double glycine leader sequence.

PMID- 18051761
TI  - Influence of aeration during propagation of pitching yeast on fermentation and
      beer flavor.
AB  - The effect of yeast propagated at different aeration conditions on yeast
      physiology, fermentation ability, and beer quality was investigated using three
      strains of Saccharomyces cerevisiae. It was shown that yeast cells grown under
      continuous aeration conditions during propagation were almost two times higher as
      compared with discontinuous aeration conditions. The maximum of cell growth of
      all samples reached between 36 h and 48 h. The concentration of trehalose was
      increased under continuous aerated yeasts, whereas glycogen was decreased. It was
      also observed that the concentration of glycogen and trehalose in yeast cells had
      no direct effect on subsequent fermentation ability. The effect of yeast
      propagated under different aeration conditions on subsequent fermentation ability
      was different from yeast strains, in which the influence will be most pronounced
      at the first fermentation. Later, the yeasts might regain its original
      characteristics in the following fermentations. Generally, continuously
      propagated yeast had a positive effect on beer quality in subsequent
      fermentation. Hence, the concentration of aroma compounds obtained with yeast
      propagated under 6 1/h for 48 h aeration was lower than those grown under other
      aeration conditions in the bottom yeasts; in particular, the amounts of
      phenylethyl alcohol, ester, and fatty acids were decreased.

PMID- 18051762
TI  - Differential stringent responses of Streptomyces coelicolor M600 to starvation of
      specific nutrients.
AB  - This study focused on the involvement of the unusual nucleotide (p)ppGpp, a
      stringent factor, during the morphological and physiological differentiation of
      Streptomyces coelicolor. Two genes, relA and rshA, were disrupted to demonstrate
      the roles of the stringent factor in the differentiation. The intracellular
      concentration of (p)ppGpp in the wild-type (M600) and disrupted mutants was
      measured in relation to the intentional starvation of a specific nutrient such as
      carbon, nitrogen, and phosphate or the in situ depletion of nutrients in a batch
      culture. As a result, it was found that the morphological characteristic of the
      deltarelA mutant was a bld phenotype forming condensed mycelia, whereas the
      deltarshA mutant grew fast-forming spores and straightforward mycelia. In both
      mutants, the production of actinorhodin (Act) was completely abolished, yet the
      undecylprodigiosin (Red) production was increased. Intracellular (p)ppGpp was
      detected in the deltarelA mutant in the case of limited phosphate, yet not with
      limited carbon or nitrogen sources. In contrast, (p)ppGpp was produced in the
      deltarshA mutant under limited carbon and nitrogen conditions. Therefore,
      (p)ppGpp in S. coelicolor was found to be selectively regulated by either the
      RelA or RshA protein, which was differentially expressed in response to the
      specific nutrient limitation. These results were also supported by the in situ
      ppGpp production during a batch culture. Furthermore, it is suggested that RelA
      and RshA are bifunctional proteins that possess the ability to both synthesize
      and hydrolyze (p)ppGpp.

PMID- 18051763
TI  - Statistical optimization of medium components for the production of biosurfactant
      by Bacillus licheniformis K51.
AB  - The nutritional medium requirement for biosurfactant production by Bacillus
      licheniformis K51 was optimized. The important medium components, identified by
      the initial screening method of Plackett-Burman, were H3PO4, CaCl2, H3BO3, and Na
      EDTA. Box-Behnken response surface methodology was applied to further optimize
      biosurfactant production. The optimal concentrations for higher production of
      biosurfactants were (g/l): glucose, 1.1; NaNO3, 4.4; MgSO4 x 7H2O, 0.8; KCl, 0.4;
      CaCl2, 0.27; H3PO4, 1.0 ml/l; and trace elements (mg/l): H3BO3, 0.25; CuSO4, 0.6;
      MnSO4, 2.2; Na2MoO4, 0.5; ZnSO4, 6.0; FeSO4, 8.0; CoCl2, 1.0; and Na-EDTA, 30.0.
      Using this statistical optimization method, the relative biosurfactant yield as
      critical micelle dilution (CMD) was increased from 10x to 105x, which is ten
      times higher than the non-optimized rich medium.

PMID- 18051764
TI  - Hydrogen sulfide removal by immobilized Thiobacillus novellas on SiO2 in a
      fluidized bed reactor.
AB  - The removal of hydrogen sulfide (H2S) from aqueous media was investigated using
      Thiobacillus novellas cells immobilized on a SiO2 carrier (biosand). The optimal
      growth conditions for the bacterial strain were 30 degrees C and initial pH of
      7.0. The main product of hydrogen sulfide oxidation by T. novellus was identified
      as the sulfate ion. A removal efficiency of 98% was maintained in the three-phase
      fluidized-bed reactor, whereas the efficiency was reduced to 90% for the two
      phase fluidized-bed reactor and 68% for the two-phase reactor without cells. The
      maximum gas removal capacity for the system was 254 g H2S/m3/h when the inlet H2S
      loading was 300 g/m3/h (1,500 ppm). Stable operation of the immobilized reactor
      was possible for 20 days with the inlet H2S concentration held to 1,100 ppm. The
      fluidized bed bioreactor appeared to be an effective means for controlling
      hydrogen sulfide emissions.

PMID- 18051765
TI  - Identification and functional analysis of vibrio vulnificus SmcR, a novel global
      regulator.
AB  - Recently, quorum sensing has been implicated as an important global regulator
      controlling the production of numerous virulence factors such as capsular
      polysaccharides in bacterial pathogens. The nucleotide and deduced amino acid
      sequences of smcR, a homolog of V. harveyi luxR identified from V. vulnificus
      ATCC29307, were analyzed. The amino acid sequence of SmcR from V. vulnificus was
      72 to 92% similar to those of LuxR homologs from Vibrio spp. Functions of SmcR
      were assessed by the construction of an isogenic mutant, whose smcR gene was
      inactivated by allelic exchanges, and by evaluating its phenotype changes in
      vitro and in mice. The disruption of smcR resulted in a significant alteration in
      biofilm formation, in type of colony morphology, and in motility. When compared
      with the wild-type, the smcR mutant exhibited reduced survival under adverse
      conditions, such as acidic pH and hyperosmotic stress. The smcR mutant exhibited
      decreased cytotoxic activity toward INT 407 cells in vitro. Furthermore, the
      intraperitoneal LD50 of the smcR mutant was approximately 10(2) times higher than
      that of parental wild-type. Therefore, it appears that SmcR is a novel global
      regulator, controlling numerous genes contributing to the pathogenesis as well as
      survival of V. vulnificus.

PMID- 18051766
TI  - Qualitative and quantitative analysis of genetically modified pepper.
AB  - For the development of qualitative and quantitative PCR methods of genetically
      modified (GM) pepper developed in Korea, a capsanthin-capsorubin synthase (CCS)
      gene was used as the endogenous reference gene. The primer pair ccs-F/R
      amplifying the pepper endogenous gene gave rise to an amplicon of 102 bp. No
      amplified product was observed when DNA samples from 16 different plants were
      used as templates. The construct-specific primer pairs amplifying the junction
      region of the bar gene and Ti7 introduced in GM pepper gave rise to an amplicon
      of 182 bp. Quantitative PCR assay was performed using a TaqMan probe and a
      standard plasmid as a reference molecule, which contained both an endogenous and
      event-specific sequence. For the validation of this method, the test samples
      containing 0.1, 1, 3, 5, and 10% GM pepper were quantified.

PMID- 18051767
TI  - Characterization of site-specific recombination by the integrase MJ1 from
      enterococcal bacteriophage phiFC1.
AB  - Bacteriophage phiFC1 integrase (MJ1) was previously shown to perform a site
      specific recombination between a phage attachment site (attP) and a host
      attachment site (attB) in its host, Enterococcus faecalis, and also in a non-host
      bacterium, Escherichia coli. Here, we investigated biochemical features of MJ1
      integrase. First, MJ1 integrase could perform in vitro recombination between attP
      and attB in the absence of additional factors. Second, MJ1 integrase interacted
      with att sites. Electrophoretic mobility shift assays and DNase I footprinting
      revealed that MJ1 integrase could efficiently bind to all the att sites and that
      MJ1 integrase recognized relatively short sequences (approximately 50 bp)
      containing an overlapping region within attB and attP. These results demonstrate
      that MJ1 integrase indeed catalyzes an integrative recombination between attP and
      attB, the mechanism of which might be simple and unidirectional, as found in
      serine integrases.

PMID- 18051768
TI  - Functions of metallothionein generating interleukin-10-producing regulatory CD4+
      T cells potentiate suppression of collagen-induced arthritis.
AB  - Metallothionein, a cysteine-rich stress response protein that is naturally
      induced by a variety of immunologic stressors, has been shown to suppress
      autoimmune disorders through mechanisms not yet fully defined. In the present
      study, we examined the underlying mechanisms by which metallothionein might
      mediate such regulation of autoimmunity. Naive CD4+ T cells from metallothionein
      deficient mice differentiated to produce significantly less IL-10, TGF-gamma, and
      repressor of GATA, but more IFN-gamma and T-bet, when compared with those from
      wild-type mice. The levels of IL-4 and GATA-3 production were not different
      between the two groups of mice. Conversely, treatment with exogenous
      metallothionein during the priming phase drove naive wild-type CD4+ T cells to
      differentiate into cells producing more IL-10 and TGF-beta, but less IFN-gamma
      than untreated cells. Metallothionein-primed cells were hyporesponsive to
      restimulation, and suppressive to T cell proliferation in an IL-10-dependent
      manner. Lymphocytes from metallothionein-deficient mice displayed significantly
      elevated levels of AP-1 and JNK activities in response to stimulation compared
      with those from wild-type controls. Importantly, transgenic mice overexpressing
      metallothionein exhibited significantly reduced susceptibility to collagen
      induced arthritis and enhanced IL-10 level in the serum, relative to their
      nontransgenic littermates. Taken together, these data suggest that
      metallothionein is able to promote the generation of IL-10- and TGF-beta
      producing type 1 regulatory T-like cells by downregulating JNK-dependent AP-1
      activity. Thus, metallothionein may play an important role in the regulation of
      Th1-dependent autoimmune arthritis, and may represent both a potential target for
      therapeutic manipulation and a critical element in the diagnostic assessment of
      disease potential.

PMID- 18051769
TI  - Interaction proteome analysis of Xanthomonas Hrp proteins.
AB  - Because of the importance of the type III protein-secretion system in bacteria
      plant interaction, its function in bacterial pathogenesis of plants has been
      intensively studied. To identify bacterial proteins interacting with Xanthomonas
      hrp gene products that are involved in pathogenicity, we performed the
      glutathione-bead binding analysis of Xanthomonas lysates containing GST-tagged
      Hrp proteins. Analysis of glutathione-bead bound proteins by 1-DE and MALDI-TOF
      has demonstrated that Avr proteins, RecA, and several components of the type III
      secretion system interact with HrpB protein. This proteomic approach could
      provide a powerful tool in finding interaction partners of Hrp proteins whose
      roles in host-pathogen interaction need further studies.

PMID- 18051770
TI  - Thermal resistance and inactivation of Enterobacter sakazakii isolates during
      rehydration of powdered infant formula.
AB  - Enterobacter sakazakii may be related to outbreaks of meningitis, septicemia, and
      necrotizing enterocolitis, mainly in neonates. To reduce the risk of E. sakazakii
      in baby foods, thermal characteristics for Korean E. sakazakii isolates were
      determined at 52, 56, and 60 degrees C in saline solution, rehydrated powdered
      infant formula, and dried baby food. In saline solution, their D-values were 12
      16, 3-5, and 0.9-1 min for each temperature. D-values increased to 16-20, 4-5,
      and 2-4 min in rehydrated infant formula and 14-17, 5-6, and 2-3 min in dried
      baby food. The overall calculated z-value was 6-8 for saline, 8-10 for powdered
      infant formula, and 9-11 for dried baby food. Thermal inactivation of E.
      sakazakii during rehydration of powdered infant formula was investigated by
      viable counts. Inactivation of cultured E. sakazakii in infant formula milk did
      not occur for 20 min at room temperature after rehydration with the water at 50
      degrees C and their counts were reduced by about 1-2 log CFU/g at 60 degrees C
      and 4-6 log CFU/ml with the water at 65 and 70 degrees C. However, the
      thermostability of adapted E. sakazakii to the powdered infant formula increased
      more than two times. Considering that the levels of E. sakazakii observed in
      powdered infant formula have generally been 1 CFU/100 g of dry formula or less,
      contamination with E. sakazakii can be reduced or eliminated by rehydrating water
      with at least 10 degrees C higher temperature than the manufacturer-recommended
      50 degrees C.

PMID- 18051771
TI  - Crystallization and preliminary X-ray diffraction analysis of BcOMT2 from
      Bacillus cereus: a family of O-methyltransferase.
AB  - O-Methyltransferases (OMTs), one of the ubiquitous enzymes in plants, bacteria,
      and humans, catalyze a methyl-transfer reaction using S-adenosylmethionine and a
      wide range of phenolics as a methyl donor and acceptor, respectively. Substrates
      for most bacterial OMTs have largely remained elusive, but recent investigation
      using BcOMT2, an OMT from Bacillus cereus, suggested that ortho
      dihydroxyflavonoids could serve as substrates. To elucidate the functional and
      structural features of BcOMT2, we expressed, and purified BcOMT2, and
      crystallized an apoenzyme and its ternary complex in the presence of a flavonoid
      and S-adenosylhomocysteine. Each crystal diffracted to 1.8 angstroms with its
      space group of C2 and P2(1)2(1)2(1), respectively. Structural analysis of apo
      BcOMT2 and its ternary complex will provide the structural basis of
      methyltransfer onto (iso)flavonoids in a regiospecific manner.

PMID- 18051772
TI  - Phosphatidylcholine is required for the efficient formation of photosynthetic
      membrane and B800-850 light-harvesting complex in Rhodobacter sphaeroides.
AB  - No phosphatidylcholine (PC) was detected in the membrane of Rhodobacter
      sphaeroides pmtA mutant (PmtA1) lacking phosphatidylethanolamine (PE) N
      methyltransferase, whereas PE in the mutant was increased up to the mole %
      comparable to the combined level of PE and PC of wild type. Neither the fatty
      acid composition nor the fluidity of membrane was altered by pmtA mutation.
      Consistently, aerobic and photoheterotrophic growth of PmtA1 were not different
      from wild type. However, PmtA1 showed an extended lag phase (15 h) after the
      growth transition from aerobic to photoheterotrophic conditions, indicating the
      PC requirement for the efficient formation of intracytoplasmic membrane (ICM).
      Interestingly, the B800-850 complex of PmtA1 was decreased more than twofold in
      comparison with wild type, whereas the level of the B875 complex comprising the
      fixed photosynthetic unit was not changed. Since puc expression is not affected
      by pmtA mutation, PC appears to be required for the proper formation of the B800
      850 complex in the ICM of R. sphaeroides.

PMID- 18051773
TI  - Kinetics properties of guaiacol peroxidase activity in Crocus sativus L. corm
      during rooting.
AB  - BACKGROUND: Guaiacol peroxidases (GP) are haem-containing enzymes participating
      in many physiological processes in plants. The expression pattern of these
      enzymes is organ-specific and developmentally regulated. METHODS: The presence of
      GP activity in extract samples, prepared from Crocus sativus L. corms that were
      either dormant or rooting for 3, 6 and 10 days, was investigated. RESULTS:
      Kinetic studies revealed a significant similarity among GP activities detectable
      in the corm at different stages of development: in all extract samples, the
      activity was maximal at pH 7.5 and after preincubation at 30-40 degrees C. When
      guaiacol was used as the varying substrate, Michaelis-Menten kinetics behavior
      was observed in all extract samples and resulted in similar KM values; catalytic
      efficiencies were also very similar. The corm GP activity was inhibited by
      cyanide, azide and ascorbate. The GP activities from different extract samples
      had the same sensitivities to azide, cyanide and ascorbate and the type of
      inhibition by azide and cyanide was competitive and uncompetitive, respectively,
      while ascorbate inhibited the GP activity non-competitively. Corm extract samples
      from different stages of rooting similarly responded to temperature treatment and
      a biphasic Arrhenius plot resulted for each extract sample studied. When dormant,
      3-, 6- and 10-days-rooting corm extracts were submitted to non-denaturing
      polyacrylamide gel electrophoresis, the GP-specific activity staining revealed
      one band on the gel, with the same migrating distances. CONCLUSION: This finding
      in combination with kinetic studies demonstrated that at least one form of GP,
      with an apparent molecular weight of 68 kDa, was expressed during development of
      Crocus sativus L. corm.

PMID- 18051775
TI  - Influence of E1-deleted recombinant adenoviruses on B7.1 and IL-2 expression in
      C1498 cells.
AB  - BACKGROUND: Knowing that adenoviral vectors could initiate innate immunity, the
      ability of E1-deleted recombinant adenovirus (Ad-E1Delta) in induction of B7.1
      and IL-2 molecules was studied. METHODS: The expression of green fluorescent
      protein in C1498 cells following transfection of these cells with adenovirus
      green fluorescent protein vector confirmed the ability of adenovirus vectors in
      infecting the cells and inducing the expression of the gene of interest. The
      expression of B7.1 molecule on the surface of the cells was assayed upon
      infection with Ad-E1Delta vector. Adenovirus-IL-2/B7.1 vector capable of inducing
      IL-2 and B7.1 expression in the cells was used as the positive control vector.
      RESULTS: According to the FACS results, about 4.17% of normal cells expressed
      B7.1 on their surface, while this level was increased in Ad-E1Delta transduced
      cells up to 14.43%. These results demonstrate that Ad E1? vector considerably
      (about 3 folds) increases the expression of B7.1 on the cells. No detectable IL-2
      was secreted into the medium of non-transduced and Ad-E1Delta transduced
      cellscells. CONCLUSION: Data indicate that the infection of C1498 cells with
      recombinant adenoviruses stimulates expression of B7.1 on the cell surface rather
      than secretion of IL-2 into the medium.

PMID- 18051774
TI  - Cloning and expression of coxsakievirus B3 viral protein-1 in E. coli.
AB  - BACKGROUND: Viral protein-1 (VP1) is a major capsid protein of Coxsakievirus B3
      (CVB3) that plays an important role in directing viruses towards permissive cells
      and acts as a main antigenic site of the virus in eliciting of host immune
      response, hence it seems VP1 can be considered as a vaccine candidate against
      CVB3 infection. In this study, cDNA of VP1 was prepared, cloned into pET
      expression vector and the recombinant protein (VP1) was over expressed in E.
      coli. METHODS: The viruses were grown in suspension cultures of Vero cells with
      an input virus multiplicity of 10-50 plaque-forming units/cell. After observing
      complete cytopathic effect, the total RNA (cells and virus) was prepared for RT
      PCR and by using specific primers, VP1 cDNA was amplified and ligated into pET
      vectors (32 a and 28 a). The recombinant vector was transferred into competent E.
      coli (BL-21) and after selection of proper colony, which carried correct cDNA
      within the vector; cells were cultured and induced with isopropyl B-D
      thiogalactopyranoside, in order to express protein (VP1). The cultures were
      tested for presence of VP1 by SDS-PAGE and Western-Blotting analysis. RESULTS:
      Molecular techniques such as PCR which showed exact defined size of the VP1 (819
      bp), restriction digestion and finally immunoblot analysis of over expressed
      protein; all confirmed the correct cloning and expression of VP1 in this
      research. CONCLUSION: In this research, full length of VP1 as major capsid
      protein of CVB3 was over expressed in E. coli which, can be used for further
      studies, including neutralizing antibody production against CVB3.

PMID- 18051776
TI  - Distribution of enterococcal species and detection of vancomycin resistance genes
      by multiplex PCR in Tehran sewage.
AB  - BACKGROUND: Enterococci are important because of their role as the leading cause
      of nosocomial infections which have a significant role in the dissemination and
      persistence of antimicrobial resistance genes. METHODS: In this study, we
      determined the distribution of enterococcal species in the sewage treatment
      plants in Iran. Furthermore, we improved a rapid and specific PCR method using
      primers (sodA and ddl genes) for identification of enterococci spp. RESULTS AND
      CONCLUSION: A total number of 712 enterococci spp. were isolated and the results
      showed that 56%, 24%, 12%, 4%, 2%, 1% and 1% isolates were E. faecium, E. hirae,
      E. faecalis, E. gallinarum, E. casseliflavus, E. mundtii and other enterococcal
      spp., respectively. The use of species-specific PCR was in agreement with the
      biochemical tests. Furthermore, multiplex PCR was developed to study the presence
      of vancomycin resistant genes in E. faecium or E. faecalis. The multiplex PCR
      appeared to be a useful, rapid and specific method for detecting and
      discriminating genotypes for vancomycin-resistant Enterococcus.

PMID- 18051777
TI  - Monitoring pyrethroid insecticide resistance in major malaria vector Anopheles
      culicifacies: comparison of molecular tools and conventional susceptibility test.
AB  - BACKGROUND: Anopheles culicifacies is a main malaria vector in southeastern part
      of Iran, bordring Afghanistan and Pakistan. So far, resistance to DDT, dieldrin,
      malathion and partial tolerance to pyrethroids has been reported in An.
      stephensi, but nothing confirmed on resistance status of An. culicifacies in
      Iran. METHODS: In current study, along with WHO routine susceptibility test with
      DDT (4%), dieldrin (0.4%), malathion (5%), permethrin (0.25%), lambadacyhalothrin
      (0.1%), and deltamethrin 0.025, we cloned and sequenced segment VI of domain II
      (SII6) in voltage-gated sodium channel (vgsc) gene of An. culicifacies specimens
      collected in Sistan and Baluchistan province (Iran). RESULTS: A 221-bp amplified
      fragment showed 91% and 93% similarity with exon I and exon II of An. gambiae.
      The size of intron II in An. culicifacies is 62 bp, while in An. gambiae is 57
      bp. The major difference within An. culicifacies specimens and also with An.
      gambiae is in position 29 of exon I, which led to substitution of Leu to His
      amino acid. CONCLUSION: This data will act as first report on partial sequence of
      vgsc gene and its polymorphism in An. culicifacies. A Leu to His amino acid
      substitution detected upstream the formerly known knockdown resistance (kdr)
      mutation site could be an indication for other possible mutations related to
      insecticide resistance. However, the result of WHO susceptibility test carried
      out in Baluchistan of Iran revealed a level of tolerance to DDT and dieldrin, but
      almost complete susceptibility to pyrethroids in An. culicifacies. We postulate
      that the molecular diagnostic tool developed for detection and identification of
      kdr-related mutations in An. culicifacies, could be useful in monitoring
      insecticide resistance in Iran and neighbouring countries such as Pakistan and
      Afghanistan. A phylogenetic tree also constructed based on the sequence of exon I
      and II, which readily separated An. culicifacies populations from An. stephensi,
      An. fluviatilis and An. gambiae.

PMID- 18051778
TI  - Effect of esophageal distention on basal and stimulated gastric acid secretion in
      rats.
AB  - BACKGROUND: It is well established that the esophageal distention (ED) leads to
      gastric relaxation, partly by vago-vagal reflex, but till now, the effect of ED
      on gastric acid secretion has not been investigated. The aim of this study was to
      investigate the effect of ED on basal and stimulated gastric acid secretion.
      METHODS: Adult male Wistar rats (200-240 g) were deprived of food but not the
      water 24 h before the experiments. Under urethane anesthesia (1.2 g/kg, i.p.),
      animals underwent tracheostomy and laparotomy. A catheter was inserted in the
      stomach through duodenum for gastric distention and gastric washout and the
      esophagus was cannulated with a distensible balloon orally to distend esophagus
      (0.3 ml, 10 min). Gastric acid secretion was stimulated by gastric distention,
      carbachol (4 microg/kg, i.p.) or histamine (5 mg/kg, s.c.). Effects of vagotomy,
      NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v.) and also hexamethonium
      were investigated. RESULTS: Basal and gastric distention- and carbachol,
      histamine-stimulated acid secretion were reduced by the ED (P<0.05, P<0.0001,
      P<0.01 and P<0.02, respectively). L-NAME (10 mg/kg, i.v.) elevated the acid
      output (P<0.002). Vagotomy reduced the inhibitory effect of the esophagus
      distention on gastric distention-induced acid secretion (P<0.01). CONCLUSION:
      These results indicate that the vagus nerves are involved in the inhibitory
      effect of the ED on the basal and stimulated gastric acid secretion. Furthermore,
      nitric oxide could be involved.

PMID- 18051779
TI  - Influence of flavonols as in vitro on low density lipoprotein glycation.
AB  - INTRODUCTION: The non-enzymatic glycation of Low density lipoprotein (LDL) is a
      naturally occurring chemical modification of apolipoprotein B as a result of
      condensation between lysine residues and glucose. Glycated LDL is poorly
      recognized by LDL receptors and initiates different processes that can be
      considered proatherogenic. Thus, LDL glycation may contribute in the increased
      atherosclerotic risk of patients with diabetes. The objective of this study was
      to investigate the effect of naturally occurring flavonols on LDL glycation in
      vitro. METHODS: In this study, LDL was isolated from EDTA-plasma by
      ultracentrifugation using a single step discontinuous gradient. Then, glucose was
      added to LDL and LDL glycation level was estimated in absence and presence of
      flavonols by sodium periodate assay. RESULTS: This study was showed that five
      flavonols: quercetin, myricetin, kaempferol, rutin and morin decreased LDL
      glycation in a dose-dependent manner. Also, it was demonstrated this nutrients
      decreased electrophoretic mobility of glycated LDL. CONCLUSION: The results of
      this investigation show that flavonols probably with their antioxidant properties
      inhibited LDL glycation and thus may have a role in ameliorating atherosclerotic
      risk of patients with diabetes mellitus.

PMID- 18051780
TI  - Determination of relationships between the ultrasound velocity and the physical
      properties of bovine cortical bone femur.
AB  - BACKGROUND: Accurate measurements of physical characteristics of bone are
      essential for diagnosis, assessment of change following treatment, and therefore,
      indirectly, for evaluation of new forms of therapy. This is particularly true of
      osteoporosis and aging skeleton, in which fractures occur easily. METHODS: In
      this study an ultrasonic system was set-up and calibrated on Plexiglas tubes of
      variable thickness then used to detect the cortical bone thickness change in calf
      and bovine adult femurs. Lamb waves have been generated and detected using a pair
      of Piezoelectric point transducers (transmitter and receiver) operating at 60 kHz
      in contact with the surface of the bone. RESULTS: A link has been established
      between the ultrasound velocity and the bone thickness. On the other hand, the
      density variation has been also investigated by the simulation of the bone
      decalcification chemically. The results show that the velocity is very sensitive
      to both thickness and density, its value reduces as the cortical bone thickness
      and density decrease. CONCLUSION: This technique might be considered in the
      attendance of certain bone diseases expressing itself by gradual change in
      physical properties.

PMID- 18051781
TI  - Designing E1 deleted adenoviral vector by homologous recombination.
AB  - BACKGROUND: Adenoviruses are used extensively to deliver genes into mammalian
      cells, particularly where there is a requirement for high-level expression of
      transgene products in cultured cells, or for use as recombinant viral vaccines or
      in gene therapy. In spite of their usefulness, the construction of adenoviral
      vectors (AdV) is a cumbersome and lengthy process that is not readily amenable to
      the generation of large collection of clones. METHODS: In this project, to delete
      E1 gene in adenovirus, an adenoviral plasmid containing lateral sites of E1
      region of adenovirus was made and recombination in the 293A cells between the
      homologous region of this linearized plasmid and the adenovirus genome resulted
      in the formation of the complete adenoviral recombinant. RESULTS: This
      recombination resulted in loss of E1 region and we constructed a recombinant
      adenovirus type 5 vector that E1 gene was deleted by homologous recombination.
      CONCLUSION: Homologous recombination is more easy and fast technique in the
      production of AdV.

PMID- 18051782
TI  - Rapid DNA extraction protocol from stool, suitable for molecular genetic
      diagnosis of colon cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most common forms of cancers in
      the world and is curable if diagnosed at the early stage. Analysis of DNA
      extracted from stool specimens is a recent advantage to cancer diagnostics. Many
      protocols have been recommended for DNA extraction from stool, and almost all of
      them are difficult and time consuming, dealing with high amount of toxic
      materials like phenol. Their results vary due to sample collection method and
      further purification treatment. In this study, an easy and rapid method was
      optimized for isolating the human DNA with reduced PCR inhibitors present in
      stool. METHODS: Fecal samples were collected from 10 colonoscopy-negative adult
      volunteers and 10 patients with CRC. Stool (1 g) was extracted using
      phenol/chloroform based protocol. The amplification of P53 exon 9 was examined to
      evaluate the extraction efficiency for human genomic targets and also compared
      its efficiency with Machiels et al. and Ito et al. protocols. RESULTS: The
      amplification of exon 9 of P53 from isolated fecal DNA was possible in most cases
      in 35 rounds of PCR using no additional purification procedure for elimination of
      the remaining inhibitors.inhibitors. CONCLUSION: A useful, rapid and easy
      protocol for routine extraction of DNA from stool was introduced and compared
      with two previous protocols.

PMID- 18051783
TI  - [In order to perform clinical trials efficiently in Japan--important issues
      regarding monitoring by sponsors].
AB  - The guideline for Good Clinical Practice (GCP) of new drugs was enforced as
      Ministerial Ordinance No. 28, dated March 27, by the Ministry of Health, Labor
      and Welfare. In Article 21 of the guideline, a sponsor shall prepare the
      operating procedures of monitoring, and perform monitoring in conformity with the
      procedures. The Pharmaceuticals and Medical Devices Agency (PMDA) performs the
      GCP review of the application of pharmaceuticals and medical devices, including
      both the document-based conformity review and on-site GCP review, in order to
      protect human subjects and ensure the integrity of data in clinical trials. The
      purpose of monitoring is to perform clinical trials ethically and scientifically.
      Important issues in monitoring raised by the GCP reviews by the PMDA are
      summarized in this study. Our findings both directly and indirectly reflect the
      verification of the GCP guidance of investigational sites. We hope that the
      appropriate monitoring will encourage investigators to perform clinical trials
      effectively, resulting in clinical trials conforming to the GCP guidelines. Our
      review will lead to more effective and safer new drugs and medical devices
      applied in Japan. This is not an official PMDA guidance or policy statement.

PMID- 18051784
TI  - [Results of a survey of community-acquired-pneumonia and evaluation of old and
      new Japanese Respiratory Society guidelines].
AB  - We evaluated the usefulness of domestic and foreign guidelines for the diagnosis
      and treatment of patients with community-acquired-pneumonia at 23 institutions in
      6 prefectures of the Tohoku Area, from December 2003 to November 2004. Based on
      the old and new Japanese Respiratory Society (JRS) guidelines, we evaluated
      severity, clinical efficacy and detection of atypical pneumonia. As for severity,
      the old guidelines led to the diagnosis of an excessive number of 'severe' cases.
      On the other hand, patients were appropriately diagnosed as having mild,
      moderate, severe, or very severe disease based on the new JRS guidelines (2005).
      The severity classification often correlated with the Pneumonia Severity Index
      (PSI) of the IDSA guidelines. The efficacy rate for patients who were prescribed
      the recommended drug according to the old JRS guidelines was 85.7% and for those
      who did not use the recommended drug it was 68.7% (p < 0.001).

PMID- 18051785
TI  - [Relationship between smoking cessation rates and underlying diseases].
AB  - PURPOSE: To compare smoking cessation rates among patients with underlying
      diseases treated with the same anti-smoking program and to analyze the
      relationship between disease entity and cessation rate, retrospectively. SUBJECT:
      Between June and December 2006, 98 patients were treated at the Nicotine
      Addiction Clinic in Nagoya Medical Center. Of these, 97 who had been covered by a
      social insurance were enrolled in this study. RESULTS: Underlying diseases were
      psychological in 18 (20%), cancer in 9 (9%). cerebrovascular in 13 (13%), and
      respiratory in 9 (9%). The overall smoking cessation rate at one month was 61%.
      Cessation rates for each underlying disease were 100% in hypertension, 100% in
      ischemic heart diseases, 100% in diabetes mellitus, 89% in cancer, 85% in
      cerebrovascular diseases, 44% in respiratory diseases, 28% in psychological
      disorders, and 17% in HIV infection. CONCLUSIONS: The most prevalent type
      underlying disease was psychological disorders. Smoking cessation rates were high
      in ischemic heart diseases, cancer, and hypertension, but low in psychological
      disorders and HIV infection.

PMID- 18051786
TI  - [The clinical significance of mast cell tryptase in bronchial alveolar lavage
      fluid in interstitial lung diseases].
AB  - Mast cell tryptase plays an important role in fibrosis. Tryptase levels in
      bronchial alveolar lavage fluid (BALF) from patients with interstitial lung
      diseases are frequently increased, but little is known of the clinical
      significance. The study population consisted of 93 patients [38 with sarcoidosis,
      23 with collagen vascular disease (CVD), and 32 with idiopathic pulmonary
      fibrosis (IPF)]. BALF tryptase levels were measured with a newly developed B12
      antibody-fluoroimmunocap method (UniCAP method), which can detect an activated
      form of tryptase. We examined the relationship between BALF tryptase levels and
      clinical parameters of the diseases. BALF tryptase was detected in 7 (18.4%)
      patients with sarcoidosis, 7 (30.4%) with CVD, and 14 (45.8%) with IPF. In
      tryptase-positive group, serum ACE levels and the numbers of BALF-mast cells and
      lymphocytes were higher than the tryptase-negative group in sarcoidosis, serum
      LDH levels were higher in CVD, and the number of BALF-lymphocyte and Hugh-Jones
      grade were higher in IPF. Furthermore, tryptase-positive IPF cases had a poorer
      outcome than the tryptase-negative group by Kaplan-Meier analysis. Tryptase in
      BALF detected with the UniCAP method may be associated with disease activity in
      sarcoidosis and CVD, and with severity and poor prognosis in IPF. BALF tryptase
      measurement may be useful in the assessment of disease activity and severity in
      various interstitial lung diseases.

PMID- 18051787
TI  - [A case of bronchocentric granulomatosis associated with Aspergillus that was
      difficult to differentiate from lung cancer].
AB  - We encountered a case of suspected bronchocentric granulomatosis (BCG) occurring
      in a COPD patient. Chest CT on admission showed a nodular shadow with indentation
      and a notch-like opacity in right S(3)a. Based on these findings, lung cancer was
      suspected. As we could not establish a definitive diagnosis, video-assisted
      thoracic surgery was performed. The histological findings of the resected
      specimen demonstrated BCG with clustering of fungal hyphae in the bronchioles. As
      the lesion was resected completely, we did not give additional treatment with an
      antifungal agent. It is difficult to differentiate BCG from lung cancer
      preoperatively. However, considering the homogeniecity of the nodule, it may be
      able to differentiate this type of lesion from lung cancer based on the feature.
      We report a rare case of a solitary nodule caused by BCG with Aspergillosis.

PMID- 18051788
TI  - [A case of desquamative interstitial pneumonia with adenocarcinoma of the lung].
AB  - A 73-year-old woman was admitted to our hospital because of dyspnea on effort and
      diffuse ground-glass opacities in bilateral lower lung fields on a chest
      radiograph. CT scans demonstrated a spiculated nodule measuring 9 mm in diameter
      in the right S3 and diffuse ground-glass opacities in bilateral lower lobes.
      Right upper lobectomy and lung biopsy of the right lower lobe were performed
      using video-assisted thoracoscopic surgery. Histological examination revealed
      adenocarcinoma in the right S3 and an accumulation of pigmented macrophages in
      the alveolar spaces of the lower lobe, which was compatible with desquamative
      interstitial pneumonia (DIP). Five months' cessation of smoking was not
      sufficiently effective for DIP. Therefore, corticosteroid therapy was started,
      and resulted in rapid improvement in symptoms, pulmonary function and CT findings
      had been achieved. It is unlikely that the lung cancer and DIP were closely
      associated etiologically, because the adenocarcinoma was located far from the
      area of DIP.

PMID- 18051789
TI  - [A case of chest pain variant asthma].
AB  - A 45-year-old woman afflicted with bronchial asthma consulted our hospital
      because of severe constricting pain at the sternal area. Her chest pain improved
      with montelukast, and she was diagnosed to have chest pain variant asthma. Chest
      pain variant asthma is rare.

PMID- 18051790
TI  - [Sjogren's syndrome with multiple bullae due to pulmonary nodular amyloidosis].
AB  - We reported a case of Sjogren's syndrome with pulmonary involvement diagnosed by
      video-assisted thoracoscopic lung biopsy. The patient was a 54-year-old woman
      with antiphospholipid syndrome. Her chest radiograph and CT scan showed multiple
      nodules with or within cystic lesions. The thoracoscopic lung biopsy specimens
      revealed nodular amyloid deposits associated with bronchiolitis. The mechanism of
      bulla formation appeared to be a check-valve mechanism caused by the narrowing of
      the airway due to bronchiolitis with mononuclear cell infiltration. She has no
      symptoms without respiratory failure or functional impairment, therefore we are
      following her closely without therapy.

PMID- 18051791
TI  - [A case of miliary tuberculosis showing acute respiratory failure during
      pregnancy].
AB  - A 36-year-old Philippine woman had had fever and general fatigue from September,
      2006 (11th week of pregnancy). She was admitted with high fever, general fatigue
      and dyspnea on October 16, 2006 (13th week of pregnancy). A chest radiograph on
      admission showed bilateral miliary shadows and ground glass shadows. She already
      had severe hypoxia on admission. As acid-fast bacilli were positive in urine
      (Gaffky 8) and sputum (Gaffky 1), we diagnosed as miliary tuberculosis and
      pulmonary tuberculosis complicated with acute respiratory distress syndrome
      (ARDS). We treated her with antituberculosis chemotherapy, corticosteroid,
      sivelestat sodium hydrate, direct hemoperfusion using a polymyxin B immobilized
      column, and mechanical ventilation, but she died due to respiratory failure. We
      emphasize that in this case pregnancy has the risk of to causing disease
      progression of miliary tuberculosis and we should treat immediately and
      intensively for miliary tuberculosis complicated with ARDS.

PMID- 18051792
TI  - [Successful corticosteroid therapy of a recurrent thymoma with pure red cell
      aplasia].
AB  - A 71-year-old man underwent extended thymomectomy with partial resection of the
      upper lobe of the left lung and pericardium for stage III invasive thymoma in
      March, 2000. Postoperative chemotherapy and radiation therapy were carried out.
      The patient did well until June 2005, when a mediastinal mass and pleural
      dissemination were detected. The recurrence of the thymoma was strongly suspected
      radiographically. Combination chemotherapy of carboplatin and paclitaxel achieved
      partial remission. About three months after the last chemotherapy, the patient
      had a severe anemia in February 2006. Based on the blood data and the bone marrow
      examination, pure red cell aplasia was diagnosed. Prednisolone treatment (50 mg
      daily) resulted in dramatic regression of recurrent mediastinal and pleural
      tumors, as well as improvement of pure red cell aplasia.

PMID- 18051793
TI  - [A case of tuberculous pleurisy with a rapid decrease in pleural effusion].
AB  - We report a rare case of tuberculous pleurisy with a rapid decrease in pleural
      effusion by levofloxacin. A 73-year-old woman admitted due to dyspnea on exertion
      of one month duration. She had aortitis syndrome which had been treated with oral
      prednisolone for 6 months. Chest roentgenogram showed left pleural effusion,
      which was exudative with lymphocyte predominance and an increased level of
      adenosine deaminase. One-week administration of levofloxacin remarkably decreased
      effusion. as demonstrated on chest roentgenogram 2 weeks after treatment. Since
      Mycobacterium tuberculosis was isolated in culture from bronchial lavage fluid
      and sputum, we prescribed antituberculous therapy with isoniazid, rifampicin and
      ethambutol. resulting in complete resolution.

PMID- 18051795
TI  - [A case of allergic bronchopulmonary aspergillosis localized in one bronchial
      segment].
AB  - A 64-year-old woman was admitted with a chest radiograph abnormality. She had no
      compliant and the results of her physical examination were normal. A chest
      radiograph showed a 25-mm area of patchy opacity in the left upper lung field.
      Chest CT demonstrated a finger-like opacity along the left B3a and c that was
      highly suggestive of mucoid impaction of the bronchi. Bronchofiberscopy revealed
      mucous plugs in left B3, in which the filariform fungul hyphae were detected by
      Grocott stain. Rosenberg's clinical criteria have been cited frequently for the
      diagnosis of allergic bronchopulmonary aspergillosis (ABPA). On the one hand his
      criteria have historical significance, but at the same time various problems have
      been pointed out. Although the patient was not given a diagnosis of ABPA based on
      Rosenberg's criteria, she was given it based on the presence of type I
      immunologic response, mucoid plugs, hyphae of Aspergillus, central
      bronchiectasis. She had localized opacity only along a segmental bronchus. Our
      report may provide valuable information on the course of ABPA.

PMID- 18051794
TI  - [Direct hemoperfusion with a polymyxin B-immobilized fiber column eliminates
      neutrophils and improves pulmonary oxygenation--a comparison of two cases with
      acute exacerbation of idiopathic pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by radiographically evident
      interstitial infiltrates predominantly affecting the lung bases and by
      progressive dyspnea and worsening pulmonary function. Acute exacerbation of IPF
      is recognized widely as an accelerated phase occurring suddenly in the course of
      IPF, which leads to a catastrophic outcome. No treatment has proven to be
      effective so far. We describe two cases of acute exacerbation of IPF which were
      treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX)
      after steroid pulse therapy. One patient died on the 21st day after direct
      hemoperfusion and the other is alive at present. The survivor showed significant
      improvement of pulmonary oxygenation correlating with a decrease in the
      neutrophil count, SP-D and KL-6 after direct hemoperfusion with PMX. On the other
      hand, the non-survivor showed no improvement of pulmonary oxygenation, SP-D and
      KL-6 despite a decrease in neutrophil count comparable with that of the survivor.
      Neutrophil count which decreased temporarily after direct hemoperfusion with PMX
      soon convert to increase in the non-survivor, which is a characteristic
      difference between two. We reached the conclusions that (1) direct hemoperfusion
      with PMX absorbs neutrophils and this mechanism is effective to improve pulmonary
      oxygenation, (2) sometimes neutrophil absorption is not enough to control
      pulmonary inflammation in patients with acute exacerbation of IPF.

PMID- 18051796
TI  - [A case of exogenous lipoid pneumonia with marked elevation of serum KL-6 and
      interstitial lung shadows due to aspiration of liquid paraffin].
AB  - A 64-year-old man who ingested liquid paraffin as a laxative for over two years,
      was admitted to our hospital with a persistent interstitial lung shadow and
      marked elevation of serum KL-6. He had no overt symptoms although his chest
      radiograph revealed ground glass opacities in the left lower lung field and right
      middle and lower lung fields. We performed fiberoptic bronchoscopy. Exogenous
      lipoid pneumonia was diagnosed based on microscopic analysis of the
      bronchoalveolar lavage fluid that revealed the presence of lipid-laden alveolar
      macrophages. We instructed the patient to discontinue liquid paraffin ingestion
      and observed his clinical course. The chest radiograph and thoracic computed
      tomography revealed a tendency to improve and serum KL-6 decreased with time.
      Serum KL-6 may be an important index of the severity of exogenous lipoid
      pneumonia.

PMID- 18051797
TI  - [A case of bronchial infection of Wangiella dermatitidis].
AB  - A 81-year-old woman was admitted to our hospital because of bloody sputum. Chest
      radiograph showed an enhanced right pulmonary hilum shadow. Computed tomography
      (CT) revealed localized bronchiectasis of the right lower lung and a nodule
      protruding into the bronchus. A parenchymal shadow was also seen distal to the
      nodule. Transbronchial biopsy revealed a cluster of yeast-like fungi and the
      bronchial lavage culture showed several olive-black colored colonies on Sabouraud
      agar. Before culture, we empirically administered fluconazole (400 mg/day) on the
      assumption of candida infection based on the yeast like microscopic findings,
      however that was not appropriate. Substitution by itraconazole (200 mg/day) made
      a slight improvement of the shadow on CT. Later polymerase chain reaction of
      specimens taken by TBLB identified the olive-black fungus as Wangiella
      dermatitidis. W. dermatitidis is a dematicious fungus sometimes causing tinea
      nigra or subcutaneous infection. In compromised patients, it causes
      phaeohyphomycosis especially in the central nerve system. In cystic fibrosis
      patients, this fungus is recognized to colonize the respiratory tract and rarely
      causes pneumonia. This case had no previous immunosuppressing disease, except for
      localized bronchiectasis which was found by CT on admission. We think this is a
      very rare W. dermatitidis infection case showing a nodular lesion in an
      immunocompetent patient.

PMID- 18051798
TI  - Adrenalectomy for metastatic adrenal tumors.
AB  - The indications for adrenalectomy in cases of metastatic adrenal tumor remain
      controversial. To clarify indications and outcomes of adrenalectomy for adrenal
      metastasis, we performed a retrospective review of all 8 patients who underwent
      adrenalectomy for adrenal metastasis between 1990 and 2006 in Asahikawa Medical
      College Hospital. The Primary tumor was renal cell carcinoma in 2 cases, and
      eccrine poro carcinoma, rectal cancer, lung cancer, melanoma, bladder cancer and
      cancer of unknown origin in 1 case each. Open adrenalectomy was performed in all
      cases, including 1 case that was converted from laparoscopic adrenalectomy. Of
      the 4 patients with solitary adrenal metastasis, 3 were considered tumor-free
      after adrenalectomy, while the remaining patient was not due to unresectable
      primary tumor. Of the 3 patients with complete resection, one remained alive as
      of 88 months after adrenalectomy but was then lost to follow-up, and the other 2
      patients remain alive 12 and 7 months after adrenalectomy. Of the 2 patients with
      other resectable metastasis who were tumor-free after removal of all metastases,
      one was alive 31 months postoperatively and the other died 23 months after
      operation. The remaining 2 cases with other unresectable metastasis died within 6
      months after adrenalectomy. At least in cases of solitary adrenal metastasis,
      adrenalectomy can be effective if other valid methods are unavailable.

PMID- 18051799
TI  - [Clinical study on renal trauma].
AB  - We analyzed 26 cases of renal trauma, which occurred during the last 7 years and
      6 months. Computed tomography was performed in all cases. Four cases were of type
      Ib, 13 cases of type II, 3 cases of type IIIa, 5 cases of type IIIb and 1 case of
      type IVa, according to the classification of renal injury by the Japanese
      association for the surgery of trauma. Conservative treatment was done in 21
      cases, selective transcatheter arterial embolization (TAE) in 4 cases, and
      surgical treatment in 1 case. Conservative treatment was effective for type I and
      II renal trauma. In the cases of type IIIa and IIIb renal trauma, open surgery
      could be avoided and the affected kidney preserved by early TAE.

PMID- 18051800
TI  - Results of extracorporeal shock wave lithotripsy for the treatment of upper
      urinary tract stones.
AB  - The treatment results of 697 renal units in 687 patients treated for upper
      urinary tract stones using a Piezolith 2500 at the Ageo Central General Hospital
      during the 5-year period between August 1999 and July 2004 were analyzed. The
      stone-free rate and the success rate were calculated according to the stone size
      and location. Univariate and multivariate logistic regression analyses were
      performed to estimate the effect of the patient age, sex, affected side, stone
      location and stone size on the stone-free rate and the success rate. Overall, the
      stone-free rate and the success rate at 3 months after treatment were 82.6% and
      91.9%, respectively. The stone-free rates in renal and ureteral stones were 60.5%
      and 88.7%, respectively. The success rates for renal and ureteral stones were
      93.6% and 91.6%, respectively. In a univariate logistic regression analysis,
      patient age and stone size were significant negative factors for both the stone
      free rate and the success rate and the stone location in ureter was a significant
      positive factor only for the stone-free rate. In a multivariate analysis, stone
      location in the ureter had a positive effect on the stone-free rate, although a
      negative effect on the success rate. Extracorporeal shock wave lithotripsy for
      upper urinary tract stones was an effective and safe treatment modality. However,
      if pre-treatment factors indicate unfavorable outcome, the other treatment
      options should be considered for the first line therapy.

PMID- 18051801
TI  - [Clinical study of the urinary tract infections due to Escherichia coli harboring
      extended-spectrum beta lactamase].
AB  - Multiple drug resistance is one of the problems associated with the treatment of
      urinary tract infection. Urine bacterial culture confirmed extended-spectrum beta
      lactamase (ESBL)-producing Escherichia coli in 56 patients in the Department of
      Urology, Hokkaido Social Welfare Association Furano Hospital. The mean age of the
      patients was 83 years, and the male-to-female ratio was 1:2. The source of
      infection was cystitis in 51 patients and pyelonephritis in 5 patients. The most
      common underlying disease was neurogenic bladder in 42 patients, and a urinary
      tract catheter had been placed in 33 patients. Before the detection of ESBL
      producing E. coli, common bacteria included E. coli, Enterococcus, and
      Pseudomonas. ESBL-producing E. coli were sensitive to the following antibiotics:
      carbapenem; cephamycin; aminoglycoside; and synthesized penicillin. ESBL
      producing E. coli are resistant to multiple drugs. The use of urinary tract
      catheterization and antibiotics for asymptomatic urinary tract infection should
      be kept to a minimum.

PMID- 18051802
TI  - Evaluation of hematuria and proteinuria positivity in relation to ageing in 6,651
      apparently healthy men and women.
AB  - We examined the positivity of hematuria and proteinuria in relation to ageing in
      6,651 apparently healthy persons (2,556 women and 4,095 men) who underwent
      multiphasic health screening in our Medical Checkup Center. Commercially
      available dipsticks were used. The time from urine collection to dipstick
      analysis was within 60 minutes. The mean age of women was 48.2 years (range 10 to
      82) and that of men was 49.9 years (range 7 to 89). Approximately 30.1, 1.5, and
      0.7% of the women had hematuria, proteinuria, and hematoproteinuria,
      respectively; and 11.4, 4.0, 1.5% of the men had the corresponding urine
      abnormalities, respectively. Hematuria was 2.6 times more common in women than in
      men, and proteinuria was 2.7 times more common in men than in women. The
      positivity of hematuria increased linearly with age in women (Rs = 0.943, P =
      0.0350). On the other hand, the positivity of proteinuria or hematoproteinuria
      was not correlated with age (P = 0.8386 and P = 0.0639, respectively). In men,
      the positivity of hematuria or hematoproteinuria was not correlated with age (P =
      0.0845 and P = 0.0845, respectively). However, the positivity of proteinuria in
      those more than 30-year age group increased linearly with age (Rs = 1.000, P =
      0.0455). The true meaning of such gender- and/or age-related differences in
      urinary abnormalities remains to be determined.

PMID- 18051803
TI  - [Extraperitoneal bilateral tubeless cutaneous ureterostomy with umbilical stoma].
AB  - In some patients with intractable symptoms from incurable pelvic cancer, for
      example, urgency, severe hematuria, fistula formation and hydronephrosis,
      palliative urinary diversion with intestinal segments may not be available.
      Percutaneous nephrostomy or indwelling of double-J ureteral stents were usually
      performed. However, they suffered catheter trouble and their quality of life
      considerably worsened. Therefore, we developed a new technique of bilateral
      extraperitoneal tubeless cutaneous ureterostomy with single umbilical stoma. It
      resulted in symptom relief in 3 patients. The advantage of this method was as
      follows. The dissection was entirely extraperitoneal. The operative time was
      short and the procedure could be performed easily. The left ureter need not be
      led behind the mesosigmoid. Finally, ostomy care was easy with only one bag.

PMID- 18051804
TI  - [Laparoscopic examination of the nonpalpable testis].
AB  - We evaluated the results and advantages of laparoscopic examination in 28
      patients with 32 nonpalpable testes. Between April 1991 and May 2006, 28
      patients, 12 months to 12 years old, with 32 nonpalpable testes underwent
      diagnostic laparoscopy under general anesthesia before surgical management of the
      testes. If the blind end of the vas deferens and/or spermatic vessels was
      observed, the diagnosis of vanishing testis was made, and no further examination
      or treatment was performed. If intra-abdominal testis was observed, laparoscopic
      orchiectomy or open orchiopexy was performed. If the internal spermatic vessels
      and vas deferens entered into the internal inguinal ring, the diagnosis of intra
      canalicular testis was made so that the inguinal canal was opened for surgical
      interventions. Of the 32 nonpalpable testes 10 were on the right side and 22 were
      on the left side (4 patients had bilateral undescended testes). There were 7
      (21.8%) vanishing, 5 (15.6%) intra-abdominal and 20 (62.5%) intra-canalicular
      testes. There were no complications related to laparoscopy. Laparoscopy can be
      safely performed to assess the location of the non-palpable testes. Another
      advantage of the laparoscopic examination is that orchiopexy or orchiectomy can
      be immediately performed after the examination to avoid a second surgery.

PMID- 18051805
TI  - [Case of retroperitoneal paraganglioma].
AB  - Paragangliomas are rare neuroendocrine tumors that arise from hyperplastic
      paraganglionic cells and occur in or near the ganglia of the autonomic nervous
      system. Paragangliomas are classed as either functional or nonfunctional based on
      production of catecholamines. We report a case of retroperitoneal nonfunctional
      paraganglioma, which was successfully resected. A 26-year-old man presented with
      complaints of a mass palpable in his left lateral region. Blood and urine
      studies, including catecholamines, were within normal limits. Computed tomography
      and magnetic resonance imaging showed a solid cystic mass in the left
      retroperitoneal space without any distant metastasis. On exploration, there was
      an encapsulated, vascular mass 10 cm in diameter. There was no pedicle and no
      connection of the tumor to the abdominal or retroperitoneal organs. Complete
      excision of the tumor was performed smoothly. The postoperative period was
      uneventful. Histological findings were of paraganglioma, and there was no
      surgical margin. The patient did not receive any further treatment. Nine months
      after surgery, there were no signs of tumor recurrence.

PMID- 18051806
TI  - [Renal cell carcinoma with malignant pleural mesothelioma after asbestos
      exposure: a case report].
AB  - A 66-year-old man visited complaining of cough and sore throat. He had been
      exposed to asbestos 43 years ago. Chest X-ray revealed left pleural effusion and
      abnormal shadow in the right lung field. Chest computed tomography (CT) showed
      multiple enhanced nodules in the right pleural cavity. Abdominal CT showed a 3-cm
      enhanced tumor in the lower pole of the left kidney. Left radical nephrectomy was
      performed. Pathological diagnosis was renal cell carcinoma. Postoperatively
      pleural biopsy was performed by using thoracoscopy. White plaque was seen at the
      costal pleura and surface of lung. Pathological diagnosis was malignant pleural
      mesothelioma based on using mesothelium-associated antibodies: calretinin (+),
      CK5/6 (+), D2-40 (+), HBME-1 (+), TTF-1 (-), MOC31 (-), CEA (-). Combination
      therapy (extrapleural pneumonectomy, chemotherapy, and radiotherapy) was
      initiated. Malignant mesothelioma is a devastating neoplasm with a strong
      etiological relationship with asbestos exposure. The incidence is rising in
      industrialized countries, with the peak expected in the year 2020. However, renal
      cell carcinoma with malignant pleural mesothelioma is very rare and this is the
      2nd case in the Japanese literature.

PMID- 18051807
TI  - [Massive residual stones after ESWL for staghorn cystine calculi were completely
      dissolved by oral administration of alkaline citrate: a case report].
AB  - A 62-year-old woman was referred to our hospital for bilateral renal stones.
      Ultrasonography (US) and computed tomography (CT) revealed bilateral staghorn
      calculi and atrophic left kidney. She had extracorporeal shock-wave lithotripsy
      (ESWL) for right renal stone during the first 6 months. However, ESWL was not
      effective and the patient did not want to continue this treatment. Her stone was
      composed of cystine. We started oral administration of alkaline citrate. Then
      massive residual stones were completely dissolved during the next 32 months.

PMID- 18051808
TI  - [Triple cancer in the urinary system: a case report].
AB  - A 74-year-old male was referred to our hospital due to microhematuria that was
      pointed out at his health check-up. Cystoscopy showed many papillary bladder
      tumors under 5 mm in size. Intravenous pyelography also showed deformity of the
      right kidney and shadow defects in the left renal pelvis. Abdominal computed
      tomography revealed an 8 cm tumor invading the renal vein in the right kidney,
      and a 3 cm tumor in the left renal pelvis. Prostate biopsy was performed with PSA
      3.4 ng/ml, and he was also diagnosed with prostate carcinoma. First, he received
      right radical nephrectomy, and secondly left nephroureterectomy and cystectomy.
      Our case should be called triple cancer because bladder cancer was thought to be
      daughter tumor of renal pelvic tumor. This is, to our knowledge, the 11th case
      report that occurred in the urinary tact, and the first case that needed total
      resection of urinary tract.

PMID- 18051809
TI  - [Carcinosarcoma of the prostate: a case report].
AB  - A 63-year-old Japanese man with a 1-month history of dyschezia and dysuria was
      referred to our hospital. Transrectal ultrasonography and magnetic resonance
      imaging demonstrated a mass involving the prostate, measuring about 6.5 cm. The
      serum prostate specific antigen was 20.3 ng/ml. By the transperineal needle
      biopsy, it was suspected to be fibrosarcoma. Total pelvic exenteration was
      performed. Histopathological examination of the tumor revealed carcinosarcoma of
      the prostate. One month after the operation local recurrence was manifested by
      perineal pain. The recurrent tumor grew rapidly with severe pain. The patient's
      condition deteriorated, and finally he died of the disease nine months after the
      operation. Carcinosarcoma of the prostate is a rare neoplasm and very aggressive.
      There is no established protocol for its treatment and its prognosis is usually
      poor. This is the 49th case reported in the literature.

PMID- 18051810
TI  - [Urinary retention caused by female urethral diverticulum].
AB  - We report a 49-year-old female who had circumferential urethral diverticulum. She
      was admitted to our department for urinary retention. A cystic lesion surrounding
      the urethra had been detected by magnetic resonance imaging. We diagnosed the
      lesion as a urethral diverticulum after injecting dye to the cystic mass from
      vagina and confirming its discharge from the urethra at the pubic side by
      urethroscopy. Transvaginal resection of the diverticulum was peformed. In
      general, 4% of female urethral diverticula cause urinary retention. On the other
      hand, 1% of female bladder outlet obstruction is caused by urethral diverticula.
      It is neccessary for us to keep in mind urethral diverticulum when we evaluate
      female patients with urinary retention.

PMID- 18051811
TI  - [Neoadjuvant and adjuvant chemotherapy with methotrexate, cisplatin and bleomycin
      for advanced penile cancer: a case report].
AB  - A 58-year-old male consulted our hospital because of penile swelling and pain
      with bilateral inguinal lymphadenopathy. Pathological examination of the penile
      tumor and right superficial inguinal lymph node biopsy demonstrated moderately
      differentiated squamous cell carcinoma with lymph node metastasis. We diagnosed
      the tumor inoperable radically and adjuvant chemotherapy with methotrexate,
      cisplatin and bleomycin was administered, followed by partial penectomy and left
      superficial lymphadenectomy. The surgical specimens showed few viable tumor
      cells. This combination chemotherapy is suggested to be effective for the
      treatment of advanced penile cancer.

PMID- 18051812
TI  - [Case of self mutilation of urethra in a Munchausen's syndrome patient].
AB  - A 33-year-old man presented with urethral bleeding and syncope. Urethroscopy
      revealed erosive lesion with bleeding at bulbar urethra. Magnetic resonance
      imaging, biopsy, and blood examination were performed, but the cause of urethral
      bleeding was not identified. By accident, chopsticks with blood ware detected in
      his ward. It was revealed that urethral bleeding was caused by self-mutilation
      with chopsticks. He consulted a psychiatrist, and was diagnosed with
      'munchausen's syndrome'.

PMID- 18051813
TI  - [New aspect of glaucoma associated with narrow chamber angle].

PMID- 18051814
TI  - [The journal impact factor in ophthalmological publications].
AB  - The journal impact factor, calculated annually by Thomson Scientific
      (Connecticut, USA), is widely used for many functions including the process of
      academic evaluation. This article reviews the current trend of the impact factor
      of journals dedicated to ophthalmology. Journals publishing a larger volume of
      articles on a broad range of topics, such as Archives of Ophthalmology, American
      Journal of Ophthalmology, and Ophthalmology, rank at the top in this aspect, and
      the majority of journals from the Europe and Japan have a lower impact factor. It
      is desirable to keep in mind inherent drawbacks of the journal impact factor and
      to use it wisely when assessing a person for tenure or grant.

PMID- 18051815
TI  - [Medial canthal anatomy and the lacrimal drainage system].
AB  - The Lacrimal drainage system has a close relationship with the orbicularis oculi
      muscle. The lacrimal sac and the lacrimal canaliculus are divided into 2
      compartments by Horner's muscle. Namely, the lacrimal sac has one part attached
      to Horner's muscle and one part unattached, and the lacrimal canaliculus has one
      part in Horner's muscle and a part out side. The upper part of the sac dilates
      during contraction of Horner's muscle and is compressed during muscle relaxation.
      On the other hand, the lower part of the sac, affected by the orbital pressure,
      is compressed during contraction of the orbicularis oculi muscle, but dilates
      during relaxation. The lacrimal canaliculus in Horner's muscle is compressed
      during contraction of Horner' s muscle, and dilates during muscle relaxation.
      However, the contraction of the Horner's muscle dilates the part of the
      canaliculus not covered by the muscle, but the muscle relaxation compresses the
      part between Horner's muscle and the medial canthal tendon. The movement of this
      part functions as a valve. In addition to this dynamic drainage, the architecture
      of the lacrimal sac and nasolacrimal duct aids the lacrimal drainage as a static
      drainage system.

PMID- 18051816
TI  - [Appositional angle closure in narrow angle eyes].
AB  - Primary angle closure glaucoma (PACG) is a vision-threatening type of glaucoma. A
      high prevalence of PACG has been reported in the Asian region. In this review
      article, we would like to introduce novel findings on appositional angle closure,
      which plays an important role in the processes of PACG, based upon a new
      classification. Also, our studies of narrow angle eyes with the use of ultrasound
      biomicroscopy(UBM) revealed interesting features of appositional angle closure.
      Our studies showed that appositional angle closure was found frequently in dark
      conditions, and also that the width and location of the angles examined were
      significantly related to the presence of appositional angle closure. The use of
      UBM enabled us to observe physiologic changes in the angle structure in dark
      conditions, and provided us important information on the pathogenesis of PACG.

PMID- 18051817
TI  - [Iris movement mediates pupillary membrane regression].
AB  - In the course of mammalian lens development, a transient capillary meshwork
      called as the pupillary membrane (PM) forms. It is located in the pupil area to
      nourish the anterior surface of the lens, and then regresses to clear the optical
      path. Although the involvement of the apoptotic process has been reported in PM
      regression, the initiating factor remains unknown. We initially found that
      regression of the PM coincided with the development of iris motility, and that
      iris movement caused cessation and resumption of blood flow within the PM.
      Therefore, we investigated whether the development of the capacity of the iris to
      constrict and dilate can function as an essential signal that induces apoptosis
      in the PM. Continuous inhibition of iris movement with mydriatic agents
      suppressed apoptosis of the PM and resulted in the persistence of PM in rats. The
      distribution of apoptotic cells in the regressing PM was diffuse and showed no
      apparent localization. These results indicated that iris movement induced
      regression of the PM by changing the blood flow within it. This study suggests
      the importance of the physiological interactions between tissues-in this case,
      the iris and the PM-as a signal to advance vascular regression during organ
      development.

PMID- 18051818
TI  - [Molecular mechanism of choroidal neovascularization in age-related macular
      degeneration].
AB  - The exudative form of age-related macular degeneration (AMD) is characterized by
      choroidal neovascularization (CNV). Retinal pigment epithelial cells (RPE)
      secrete various angiogenesis-related factors, especially vascular endothelial
      growth factor (VEGF) and pigment epithelium-derived factor (PEDF). The imbalance
      between the VEGF and PEDF secreted by RPE is a key contributor to the development
      of CNV in AMD. The earliest clinical hallmark of AMD is the presence of drusen.
      Although drusen are an epidemiological risk factor for the development of CNV,
      the mechanism of how drusen induce the development of CNV remains unclear. Recent
      proteome analysis demonstrated that amyloid beta (Abeta) deposition was specific
      to drusen from eyes with AMD. We focused on Abeta and investigated the effect of
      Abeta on cultured human RPE cells as well as ocular findings in neprilysin gene
      disrupted mice, which leads to an increased deposition of Abeta. Our study
      demonstrates that Abeta accumulation affects the balance between VEGF and PEDF in
      the RPE, and reproduces features characteristic of human AMD, such as RPE atrophy
      and basal deposit formation in neprilysin gene-disrupted mice.

PMID- 18051819
TI  - [Erythropoietin as a retinal angiogenic factor in proliferative diabetic
      retinopathy].
AB  - Although retinal neovascularization in proliferative diabetic retinopathy(PDR) is
      a major cause of legal blindness, its mechanism is not fully understood. In this
      study, we focused on the angiogenic activity of erythropoietin (Epo) and
      evaluated its potential role in treating retinal angiogenesis in PDR. METHODS: We
      measured Epo and vascular endothelial growth factor (VEGF) levels in the vitreous
      fluids of 73 PDR patients and 71 nondiabetic (NDM) patients. We evaluated Epo
      expression and regulation in retinal neovascularization with soluble Epo
      receptor. RESULTS: The vitreous Epo level was significantly higher in patients
      with PDR than in NDM patients. Multivariate logistic-regression analyses
      indicated that Epo and VEGF were independently associated with PDR and that Epo
      was more strongly associated with PDR than VEGF was. The blockade of Epo
      inhibited retinal neovascularization in vitro and in vivo. CONCLUSIONS: Our data
      suggest that Epo is a potent angiogenic factor that acts independently of VEGF
      during retinal angiogenesis in PDR.

PMID- 18051820
TI  - [Relationship between proliferative diabetic retinopathy and sleep-disordered
      breathing].
AB  - PURPOSES: To investigate the prevalence of sleep-disordered breathing (SDB) in
      proliferative diabetic retinopathy (PDR) patients and clarify the relationship
      between SDB and PDR. SUBJECT AND METHODS: Sixty-four PDR patients who had
      undergone vitrectomy in our hospital were included in this study. Forty-two
      patients were male, and 22 were female. Pulseoximetry was conducted during the
      nighttime; the sleeping 3% oxygen desaturation index (ODI/h) was calculated. If
      ODI was > or = 10/h, SDB was diagnosed. Blood glucose control and the presence of
      hypertension and albuminuria were evaluated and compared between the SDB and non
      SDB groups. RESULTS: Fifty percent of male patients, 27% of female patients and
      42% of all PDR patients were diagnosed as having SDB. The presence of
      hypertension and albuminuria was 96% and 74%, respectively, in the SDB group,
      both significantly higher than in the non-SDB group. There were no significant
      differences between the two groups in preoperative HbAlc levels. However,
      compared with the non-SDB group, the prevalence of insulin therapy was
      significantly higher in the SDB group. CONCLUSION: PDR cases had a high frequency
      of SDB. It appears that SDB might hamper blood glucose control, raise the
      occurrence of hypertension and albuminuria, and is thus related to the
      progression of diabetic retinopathy.

PMID- 18051821
TI  - [A case of Leber's hereditary optic neuropathy in a female patient with the
      recrudescence of hyperthyroidism].
AB  - BACKGROUND: Thyroid hormone increases oxygen consumption and regulates
      mitochondrial biogenesis. On the other hand, in Leber's hereditary optic
      neuropathy(LHON), retinal ganglion cells are exposed to the oxidative stress
      generated during the process of adenosine 5'-triphosphate (ATP) synthesis,
      eventually leading to a loss of vision. Although there is a possibility that the
      thyroid hormone may have a role in the development or the course of LHON, no case
      has been reported indicating a relation between them. We report a female case
      with LHON who also presented exacerbation of hyperthyroidism during the course of
      the disease. CASE: The patient was a thirty-nine-year-old woman who complained of
      bilateral loss of vision. Her corrected visual acuity was 0.2 in the right eye,
      and 0.1 in the left. Fundus examination showed characteristic findings of LHON in
      both eyes. The blood free thyroxin(FT4) level at that time was abnormally high.
      The diagnosis of LHON was confirmed by the presence of mitochondrial DNA mutation
      at the nucleotide position 11778. Her visual acuity improved after one month of
      FT4 normalization. A year later, her corrected visual acuity recovered to 0.9 in
      the right eye and 1.0 in the left. CONCLUSION: Hyperthyroidism may be a trigger
      in the development of LHON.

PMID- 18051822
TI  - [Genetics in ischaemic heart disease].
AB  - The role of genetic factors in the pathogenesis of ischaemic heart disease has
      recently raised a considerable interest among researchers. Numerous
      investigations aim at finding variants of genes which might be responsible for
      increasing the risk of this illness. Many studies investigate polymorphic
      variants of genes whose protein products contribute to the genesis and
      development of atherosclerosis of coronary arteries, thrombogenesis and
      fibrinolysis and other processes significant for the progression of ischaemic
      heart disease. Genes whose polymorphisms are potentially connected with a given
      illness are called genes candidates. In ischaemic heart disease the most often
      analyzed genes are those connected with metabolism of lipids, the coagulation and
      fibrinolytic system and the renin-angiotensin-aldosterone system. Factors of
      inflammation (cytokines, TNF), proliferation of smooth muscles cells and
      vasoactivation are also important. The analysis of genetic multifunctional basis
      of the disease is rather difficult. Manifestation of the illness is connected
      with accumulation of several genetic determinants, while the clinical picture is
      additionally modified by environmental factors. Studies of genetic
      etiopathogenesis of ischaemic heart disease may result in effective prevention
      and treatment in particular patients.

PMID- 18051823
TI  - [The some risk factors for atherosclerosis in men with coronary artery disease
      depending on the age].
AB  - The aim of this study was to search to the factors favouring the earlier
      revealing of a coronary artery disease by comparing selected immunological,
      hormonal and biochemical parameters between two groups--younger and older men
      with coronary artery disease and with responding control groups. MATERIAL AND
      METHODS: In the study were included 93 men--60 with stable angina, confirmed by
      coronarography (at least 6 months after CABG, PTCA or myocardial infraction, with
      EF > 40%) and 33 men without atherosclerotic changes in the coronary vessels, as
      the control group. The two groups were divided depending on age: the younger
      subgroups [under 60-ty years old--group A with CAD (n=30) and B without CAD
      (n=18)] and the older subgroup [over 70-ty years old group C with CAD (n=30) and
      D without CAD (n=15)]. RESULTS: Significantly lower concentration were noted for
      TNF-alpha--in control groups--by about 50% in the younger and 23% in the older
      group (r = 0.49) and homocysteine (by about 20% and 22% respectively, r = 0.40).
      Patients with CAD had higher concentration of CRP then in the control groups (by
      52% and 54%, r = 0.28). Weak but positive correlation with the presence of a
      coronary heart disease was show for IgE and anti-gliadin antibodies (r = 0. 22
      0.29). CONCLUSION: The younger and older men with CAD statistically significantly
      differed in concentration of TNF-alpha and homocysteine.

PMID- 18051825
TI  - [Food challenges in children with asthma].
AB  - Food-induced symptoms are often reported and increasing problem, also for
      children with asthma. Evaluation of the possibility of concomitant food allergy
      in patients with asthma and implementation of adequate therapy can improve
      quality of life in these patients. The aim of the study was to evaluate the
      prevalence of IgE food allergy and the influence of food allergen ingestion on
      the course of asthma in children allergic to inhalant allergens during food
      challenges. MATERIAL AND METHODS: The study performed in 304 children with atopic
      asthma (age: 5.5-18 years, mean 9.5 +/- 4.69 years) was directed towards the
      possibility of concomitant food allergy. In each child a detailed questionnaire
      examination, skin prick tests with food allergens, double-blind placebo
      controlled food challenges (DBPCFC) were performed, and the level of specific IgE
      was determined (Unicap 100). RESULTS: On the basis of questionnaire data
      suspicion of food allergy was determined in 164 (66.9%) children. Skin prick
      tests with food allergens were positive in 36 (21.9%) children. Specific food IgE
      were detected in 40 (24.4%) children. DBPCFC were performed in 70 children with
      atopic asthma. IgE-related food allergy was diagnosed in 24 (9.8%) children with
      asthma. The most frequent complaints during food challenges were gastrointestinal
      symptoms and exacerbation of atopic eczema; exacerbation of asthma, mainly in the
      form of cough were determined in 11 (4.5%) children; egg appeared to be the most
      common food associated with a positive challenge result. CONCLUSIONS: Food
      allergy more often occurred in children with asthma and concomitant skin and
      gastrointestinal disorders than in those only with asthma. The diagnosis of
      possible concomitant food allergy should be considered in children with asthma.

PMID- 18051824
TI  - [Interferon gamma (IFN-gamma) level in broncholaveolar lavage (BAL) fluid is
      positively correlated with CD4/CD8 ratio in selected interstitial lung diseases].
AB  - IFN-gamma a potent antifibrotic activity in interstitial lung diseases (ILD). T
      cells, both Th1 and Tc1, are considered to be the main local source of IFN-gamma.
      MATERIAL AND METHODS: BAL fluids of 98 patients with ILD, incl. idiopathic
      pulmonary fibrosis (IPF/UIP), sarcoidosis, extrinsic allergic alveolitis (EAA),
      asbestosis and silicosis (n=16, 49, 7, 10, 16 resp.) were tested with ELISA for
      IFN-gamma levels. Results were compared with BAL cytoimmunology and patients'
      clinical data. RESULTS: Significantly increased IFN-gamma levels were found in
      non-treated patients with EAA (7.8 +/- 2.1), IPF (6.1 +/- 1.8), Loefgren's
      syndrome, LS (11.9 +/- 2.6) and progressive sarcoidosis, PS (6.4 +/- 1.2, p <
      0.05 for all), whereas the results in pneumoconioses were comparable to those
      obtained in controls (2.0 +/- 1.1 pg/ml, median +/- SEM). IFN-gamma results were
      positively correlated with total number of CD4+ cells (r(s) = +0.38, p < 0.05),
      CD4+ cells percentage (r(s) = +0.32, p < 0.005) and CD4+/CD8+ ratio (r(s) =
      +0.38, p = 0.0007), but negatively correlated with CD8+ cell percentage (r(s) = 
      0.39, p < 0.0005). In IPF patients with CD4/CD8 < or =1 (n=9) IFN-gamma level was
      lower as compared with the group with CD4/CD8 >1 (n=7), 2.8 +/- 1.3 vs. 7.3 +/-
      1.0 pg/ml. In sarcoidosis, IFN-gamma level did not seem to have a prognostic
      role, since values obtained in PS did not differ remarkably from those in stable
      sarcoidosis and LS. Moreover, subsequent steroid treatment in 7 patients with
      progressive sarcoidosis did not change significantly IFN-gamma levels in BAL
      fluid. CONCLUSIONS: Increased IFN-gamma level was found in non-treated patients
      with IPF, Loefgren's syndrome and progressive sarcoidosis. CD4+ (Th1), but
      neither CD8+ (Tc1) nor NK cells seem to be the main local source of IFN-gamma in
      ILD. Relatively low CD4/CD8 ratio in ILD may indicate the patients with increased
      risk of lung fibrosis.

PMID- 18051826
TI  - [Evaluation of bronchial hyperreactivity in children with asthma undergoing food
      challenges].
AB  - It has been shown that food allergy does not always manifest within the
      respiratory tract in such as obvious way as: dyspnea, cough or wheezing. The aim
      of the study was to evaluate the influence of food allergens on bronchial
      reactivity in children with asthma challenged with food. MATERIALS AND METHODS: A
      total of 304 patients (age range 5.5 to 18 years, mean 9.5 +/- 4.69 years) with
      atopic asthma were evaluated for food allergy by means of questionnaire, skin
      prick testing with food allergens, specific IgE tests (Unicap 100) and double
      blind placebo-controlled food challenge (DBPCFC). Bronchial hyperreactivity was
      measured by methacholine inhalation challenges performed before and after DBPCFC
      in 70 asthmatic patients suspected of food allergy. RESULTS: IgE-related food
      allergy was confirmed by DBPCFC in 24 asthmatic children. The mean FEV1 before
      and after food challenges in the group with IgE-related food allergy, as well as
      in the group without IgE-related food allergy, was not significantly different (p
      > 0.05). The mean PC20 in IgE-related food allergy group was 1.41 +/- 1.12 mg/ml
      and 0.86 +/- 0.71 mg/ml before and after food challenge respectively which was
      significantly different (p < 0.05). In the group without IgE-related food allergy
      the mean PC20 was 1.93 +/- 1.68 and 2.02 +/- 1.75 before and after challenge
      respectively (p > 0.05). CONCLUSIONS: IgE-related food allergy was present in
      9.8% children with asthma. Prevalence of respiratory manifestations induced by
      foods in children with asthma is 4.1%. Food challenges in these children
      increased bronchial reactivity, without exacerbation. Evaluation of food allergy
      in patients with asthma is indicated.

PMID- 18051827
TI  - [Estimation of pulse pressure in subjects with metabolic syndrome].
AB  - The occurrence of the metabolic syndrome (MS) increases the cardiovascular risk
      in comparison with healthy subjects. The pulse pressure (pp) is an independent
      risk factor for cardiovascular complications. The aim of the study was to
      evaluate the pulse pressure in subjects with MS accompanied or not by
      cardiovascular diseases. Material and methods. The study comprised 104 subjects
      with MS aged 48.65 +/- 7.89 years--group I; 477 clinically healthy subjects aged
      45.75 +/- 4.68 years--group II; 137 subjects with MS accompanied by
      cardiovascular diseases aged 60.05 +/- 12.77 years--group III; 94 subjects with
      cardiovascular diseases without MS aged 57.80 +/- 9.67 years--group IV. Metabolic
      syndrome was diagnosed on the basis of NCEP ATP III criteria. Increased value of
      pulse pressure (pp) was above 63 mmHg. RESULTS: Increased values of pp (> 63
      mmHg) were found in 20.2% subjects with MS--group I, in 7.1% clinically healthy
      subjects--group II, in 40.88% subjects with MS accompanied by cardiovascular
      diseases and in 36.17% subjects with cardiovascular diseases without MS.
      CONCLUSIONS: Pulse pressure is simple and helpful method in assessment of
      vascular changes and cardiovascular risk in subjects with MS. In subjects with
      cardiovascular diseases with and without MS, increased values of pulse pressure
      are found in similar percentage of cases.

PMID- 18051828
TI  - [The effectiveness of treatment with trazodone in patients with primary insomnia
      without and with prior history of hypnotics use].
AB  - The treatment of primary insomnia frequently lasts longer than four weeks, the
      maximal time allowed for daily hypnotics use. Antidepressants are important
      alternative for long-term insomnia treatment. The aim of the study was compared
      the efficacy of trazodone in the treatment of patients with primary insomnia with
      and without prior history of hypnotics use. MATERIAL AND METHODS: 28 patients (9
      M/19 F, mean age 55.9 +/- 11.8) were treated with trazodone, dose 25-150 mg/d,
      for three months. Before the start of the treatment the patients were observed
      for seven days without pharmacological treatment to exclude the hypnotics
      dependency. The Athens Insomnia Scale (AIS), the Sheehan Disability Scale (SDS),
      the Clinical Global Impression (CGI), the Leeds Sleep Questionnaire (LSEQ) were
      completed before (Day 0) and after each month of treatment (Day 30, 60, 90).
      Additionally the patients completed the sleep diaries and two actigraphic
      recordings for seven days were performed. RESULTS: The treatment with trazodone
      decreased the score in the AIS (13.5 +/- 2.4 vs. 6.3 +/- 4.3 points; p < 0.001),
      increased the sleep time (5.1 +/- 1.3 vs. 6.1 +/- 0.9 hours; p < 0.001) and
      decreased the sleep latency (82.0 +/- 69.2 vs. 45.9 +/- 41.2 minutes; p < 0.01)
      from sleep diaries. No significant differences were observed between the patients
      with and without prior history of hypnotics use. Significant improvement was
      observed also in all other used scales. Only the actigraphic recordings provided
      no significant changes during the trazodone treatment. CONCLUSION: Trazodone
      improves sleep quality and daytime functioning independently from prior history
      of hypnotics use.

PMID- 18051829
TI  - [Estimation of medical protocol correctness in the light of opinions issued as
      ordered by the judiciary or prosecution authorities].
AB  - Medical personnel, most commonly physicians, are held responsible for situations
      in which in the course of medical treatment some adverse effects develop that
      endanger the patient's health and life. Such effects generally include death, a
      severe damage to patient's health as well as the exposing of patients to the
      danger of such effects developing in them. The effects of the kind result either
      from some medical malpractice or from medical personnel's negligence. The aim of
      the paper was to analyse medico-legal expertises issued as ordered by the Polish
      Judiciary and Prosecution Authorities in cases of alleged medical malpractice
      that had been issued by the Chair and Department of Forensic Medicine, Medical
      University of Gdansk, and to compare the results with those from similar studies
      done by Chairs and Departments of Forensic Medicine at the Medical Universities
      of Katowice, Krakow, and Wroclaw. MATERIAL AND METHODS: Analysis was done of 372
      medico-legal expertises issued in the years 1990-2004 by the Chair and Department
      of Forensic Medicine, Medical University of Gdansk. The results obtained were
      compared with those from a similar analysis of medicolegal expertises issued in
      Gdarisk in the years 1968-1977 and also with those from studies presented by
      Departments of Forensic Medicine at the Medical Universities of Katowice, Krakow,
      and Wroclaw. RESULTS: Legal proceedings were generally conducted by the Public
      Prosecutor's Office, less frequently by the police, and only in 7.2% were such
      cases subject to the civil law procedure. Most frequently assessed health care
      facilities included hospitals (66.1%), clinics of medical universities (16.6%),
      and ambulance service (13.4%). Seldom were the charges of medical malpractice
      brought against basic health care facilities (9.4%) or private practices (3.5%).
      As revealed in the analyzed material, adverse health effects of a disease or
      injury included death--70.5%, a severe damage to patient's health--9.1%, and the
      endangering of patients with development of such effects--0.4%. In 60.8% of the
      cases analyzed, medical protocol implemented by medical personnel was assessed as
      proper. Medical malpractice were found in 18.5% of the cases, including
      diagnostic malpractice--1.8% therapeutic malpractice--2.7%, and those of logistic
      nature--4%. Similar results were obtained by the above mentioned Departments of
      Forensic Medicine. Negligence in the rendering of health care was found in 13.4
      of the medico-legal expertises analyzed. Conclusions. In the material subjected
      to this analysis criminal cases are predominant. Medical personnel, including
      medical practitioners, are more and more frequently charged with exposing
      patients to the immediate danger of loss of life or a severe damage to their
      health (Art. 160 of the Polish Penal Code). There are more and more cases in
      which the adverse effects endangering patient's health or life result from
      negligence rather than from some medical malpractice.

PMID- 18051830
TI  - [Chronic intestinal ischemia--not rare cause of abdominal pains--case
      description].
AB  - Chronic intestinal ischemia is a diagnostic problem for the physicians from
      internal department as well for the surgeons. The clinical manifestation of this
      disease is not clear and the symptoms are similar to many other disorders. This
      requires from the physician a wide knowledge and many-sided diagnostic process.
      The success depends also on the good cooperation between radiologist and vascular
      surgeon. The authors presents the case of 59-aged patient with occlusion of
      superior mesenteric artery. After the angioplasty there was a complete relief of
      ischemic symptoms.

PMID- 18051831
TI  - [Heart rate turbulence--a new predictor of sudden cardiac death].
AB  - Prevention of sudden cardiac deaths (SCD) is one of major challenges of todays
      cardiology. Factors, that would permit identification of patients with highest
      risk of SCD, have been sought for many years now. Although ventricle-dependent
      sinus arrhythmia has been observed for a few decades, quantification of this
      phenomenon was performed by Schmidt et al., who introduced new concept of heart
      rate turbulence (HRT). HRT parameters comprise of turbulence onset (TO) and
      turbulence slope (TS). When no HRT is observed, SCD risk is markedly increased.
      The mechanism behind HRT is not fully known, but it is though to be caused by
      baroreflex sensitivity. This factor has been evaluated in many clinical studies
      aiming at determining methods of analysis and usefulness of HRT also in others
      pathological entities. This paper is a short review of these studies.

PMID- 18051832
TI  - [Endothelium--characteristics and functions].
AB  - Endothelium is more and more likely to be considered as the biggest endocrine
      gland of human body. According to number, mass, surface of endothelial cells in
      adolescent, ability of synthesis and release of substances with multidirectional
      biological functions, endothelium should be treated as integral organ.
      Endothelial cells form barrier between blood and smooth muscle cells, playing
      crucial role in regulation of vasomotorics, hemostasis, angiogenesis,
      inflammatory processes and immunology. Strategic localization places endothelial
      cells in very first line of contact with cells and substances migrating from
      blood to tissue. Endothelium, via large number of yet not in-depth known
      mechanisms, can react to changes in pressure, blood flow and gas concentration.
      It is an easy stimulated and fast reacting structure, capable of quick activation
      and change in its own function. Mechanical damage, or loss of functional
      integrity, disturbs homeostasis of microenvironment, leading to development of
      pathological states, like hypertension, atherogenesis, thrombotic lesions,
      disturbances in perfusion of tissue and organs. The aim of this study was rewiev
      of the role of endothelial cells in vasomotorics, hemostasis, tumorgenesis and
      angiogenesis.

PMID- 18051833
TI  - [Treatment of liver failure using tissue engineering techniques].
AB  - Liver transplantation is the only efficient method of treatment of liver failure.
      Short time between liver end-stage insufficiency and transplantation procedure is
      the main problem limiting the number of liver transplants. In this paper the
      methods of liver support in patients awaiting a liver transplant using tissue
      engineering techniques were introduced. The methods of liver support using
      bioartificial liver and isolated hepatocytes transplantation were described.

PMID- 18051834
TI  - [Colorectal cancer chemoprevention].
AB  - Colorectal cancer (CRC) is the second most common malignancy in the world and a
      leading cause of cancer death. Prevention can lead to decreased incidence of this
      neoplasm. Chemoprevention may be one option. The article presents a summary of
      the main information on CRC chemoprevention based on internet database MEDLINE.

PMID- 18051835
TI  - [Stress oxidative in schizophrenia].
AB  - Etiopathogenesis of schizophrenia development is unknown yet in 1% of human
      population. There is damaged metabolism of biological membranes, abused
      production of free radicals and altered activity of antioxidant enzymes in
      patients with schizophrenia. Recently, a study showed that many of the genes and
      proteins whose expression is modified in the schizophrenic brain are related to
      glutathione and oxidative stress pathways. According to the researchers changes
      in permeability of biological membranes in brain could involve the
      pathophisiology of all--subtypes of schizophrenia as a result of oxidative
      stress. Brain is particularly sensitive to oxidative damage. There is a lot of
      phospholipids and polyunsaturated fatty acids in brain tissue under physiological
      conditions. The changes in polyunsaturated fatty acids metabolism, increased
      lipid peroxidation and the presence of oxidative stress are found in
      schizophrenia. They can course to appear instabilities of neuron membranes or
      even cell death owing to oxidative stress. Mainly to getting to know the
      molecular disease mechanism is associated with a disorder of the brain. The
      results suggest that at least some of the schizophrenia disease process can be
      traced in peripheral tissue like plasma, blood cells or liver. In various types
      of schizophrenia antipsychotic treatment affects oxidative state of erythrocyte
      membranes in a different way. Research into changes of antioxidant enzymes level
      during the treatment of typical and atypical neuroleptic drugs could contribute
      to widening the knowledge on the reasons of undesirable effects during
      pharmacotherapy with typical neuroleptic drugs.

PMID- 18051837
TI  - [Results of implementation of the subprograms "Goal-oriented medical examination
      of the Moscow population for early tuberculosis detection"].
AB  - The implementation of the subprograms "Goal-oriented medical examination of the
      Moscow population for early tuberculosis visage a differential screening of the
      population in relation to the risk of tuberculosis; fitting of health care
      facilities with current digital fluorographic equipment; improvement of an
      epidemiological screening of patients with tuberculosis. Over 7 years of
      implementation of the Program, advances were made: the population's coverage with
      preventive examinations increased by 11%; that of detively; the active detection
      of patients with respiratory abnormalities and those with pulmonary tuberculosis
      increased by 2.0 and 2.4 times, respectively; the proportion of tuberculosis
      patients actively detected rose by 1.5 times; 151 digital fluorographs and 11 X
      ray units were purchased; a program for machine fluorography study accounting was
      worked out.

PMID- 18051836
TI  - [Masked depression--history and present days].
AB  - Masked depression is a special form of an atypical depression. In the 70's and
      80's years it was often identified at patients who complained on somatic
      diseases, without any distinguishable organic disorder. Depression symptoms were
      of secondary importance, with lesser intensification, some of them didn't appear
      at all. The psychiatrists of the time created a lot of terms to describe them,
      i.e.: a depression equivalent, a vegetative equivalent, a depression without a
      depression, a hidden depression. Current classifications: ICD-10 (International
      Classification of Diseases, 10th Revision) and DSM-IV (Diagnostic and Statistical
      Manual of Mental Disorders, 4th Edition, published by the American Psychiatric
      Association) do not contain the term masked depression. It doesn't mean that have
      disappeared the problem of atypical depression syndrome with a picture
      significantly different from the commonly known. The american scientists claim
      that such group contains 6-7% of depression disorders. The lack of proper
      diagnosis and disease entity qualification leads to serious somatic and
      psychological consequences for patients. Improper diagnosis and treatment of a
      patient limits his or her social and professional life, forms suicide rate and
      makes high costs of diagnosis and treatment.

PMID- 18051838
TI  - [Adolescence tuberculosis in Moscow: epidemiological situation and problems].
AB  - The paper provides the data of analysis of antituberculous care to teenagers in
      Moscow and characterizes its problems. Emphasis is placed on the tense and
      unstable situation associated with the detection of the disease in this age
      group. In the bulk of adolescents, the disease is identifies when they come to
      see a doctor, including at somatic hospitals. Active tuberculosis detection
      techniques (tuberculin diagnosis and fluorography) fail to produce adequate
      effect mainly due to organizational problems (the bulk of teenagers are outside
      the organized collective bodies or the latter are frequently changed; the
      detection of tuberculosis in Moscow nonresidents or in whose who enter secondary
      specialized colleges claims attention). Age-related sociomedical risk factors,
      such as hormonal rearrangement, comorbidity, a negative attitude towards
      preventive medical measures, deviant behavior, social family, and dysadaption,
      are of importance for the development of tuberculosis. A sociomedical portrait of
      an adolescent with tuberculosis is given. Attention is drawn to the fact that on
      implementing antituberculous measures, it is a need for an interaction of a
      tuberculosis-controlling service with general care health network facilities,
      including those that deal with the problems of social diseases and educational
      establishments.

PMID- 18051839
TI  - [The centralized mycobacteriological laboratory is a necessary component of a
      phthisiological service in large towns of Russia].
AB  - The paper presents the main points of the authors' own concept of the
      centralization of mycobacteriological service in large towns of the Russian
      Federation. The main points of step-by-step organizational and methodological
      measures required to solve this problem are described in detail. Consecutive
      measures to realize the proposed mycobacteriological service centralization model
      originated in January 2004 on a model of the Moscow Eastern Administrative
      District with 1380 thousand inhabitants are described.

PMID- 18051840
TI  - [Types of skin lesions in pulmonary sarcoidosis and their prognostic value].
AB  - When sarcoidosis is suspected, a patient should be meticulously examined for
      dermal changes, the favorite sites of which are the skin of the face, ears, upper
      and lower extremities, and trunk. Elements may vary in number from solitary to
      multiple. When dermal changes are suspected of sarcoidosis, a dermatologist
      should examine the patient and, if there are some doubts about the nature of
      dermal elements, biopsy and histological study should be made since the
      morphological verification of the diagnosis primarily requires the use of
      extrapulmonary sites of the process, namely superficial peripheral lymph nodes,
      as well as the skin. The findings suggest that skin sarcoidosis characterized by
      the long-term chronic or progressive course is encountered at different (X-ray)
      stages of sarcoidosis of respiratory organs and is of poor prognostic value. The
      severity of dermal manifestations is no less and, in individual cases, more
      significant than pulmonary symptoms. Great or ugly skin lesions require
      prednisolone treatment. In some cases, long-term therapy cannot yield a result.
      Delagil treatment of dermal manifestations remains to be effective.

PMID- 18051841
TI  - [Investigation of Mycobacterium tuberculosis sensitivity to fluoroquinolone, by
      revealing gyrA gene mutations].
AB  - The resistance of Mycobacterium tuberculosis (MBT) to fluoroquinolones is
      associated with the mutations concentrated in the gyrA gene that is a structural
      gene of a gyrase A subunit. Detection of mutations in this portion of the gene
      allows the sensitivity of MBT to this group of drugs to be rapidly determined.

PMID- 18051842
TI  - [Opportunistic fungi isolated from patients with pulmonary tuberculosis
      (characterization of species)].
AB  - The species composition of pathogenic fungi isolated from various clinical
      materials was studied in the diagnosis of respiratory mycotic infections in
      patients with tuberculosis. The paper presents data on the composition of
      detected opportunistic microscopic fungi from a group of likely pathogens of
      bronchopulmonary mycoses, as well as fungi that have pronounced toxicogenic and
      allergenic properties.

PMID- 18051844
TI  - [Role of prophylactic programs in students' health care].
AB  - Clinical and epidemiologic methods determined real incidence of major chronic
      noninfectional diseases and certain risk factors in students. The data obtained
      prove unfavorable health state of the young people, necessity of regular
      prophylactic medical examinations that could serve for early diagnosis.

PMID- 18051843
TI  - [Chemical hair analysis in ore-dressing and processing plant workers].
AB  - The article presents results of studies covering elements content of hair and
      mineral bone density among workers engaged into Utchalinsky ore-dressing and
      processing enterprise (Utchaly town, Bashkortostan Republic) and among residents
      of copper-zinc geochemical province. Finding is dysbalance between levels of
      essential and toxic elements in hair, that is due to environmental and
      occupational factors. Analysis of elements homeostasis and mineral bone density
      could be recommended for early diagnosis of osteoporosis.

PMID- 18051845
TI  - [Physician continuing education on occupational diseases as an integral part of
      the national project "Health Promotion"].
AB  - The author's concepts are evaluated positively and additional organizational and
      practical recommendations are suggested to increase quality of doctors'
      postgraduate training in occupational therapy.

PMID- 18051846
TI  - [Cardiovascular diseases in workers engaged into metal mining industry and
      mechanical engineering].
AB  - Peculiarities of cardiovascular diseases among workers exposed to noise and
      vibration include hyperkinetic hemodynamic type supporting early terms of
      cardiovascular functions disorder. Veloergometry and echocardiography are highly
      informative and diagnostic value, so helpful in early diagnosis of circulatory
      disorders. The authors specified objective criteria of risk associated with
      occupationally related cardiovascular diseases.

PMID- 18051847
TI  - [Predictive value of endopulmonic cytogram in pulmonary tuberculosis among
      workers having concomitant chronic bronchitis and engaged into industry with
      pneumoconiosis hazard].
AB  - The study covered influence of quartz industrial dust and concomitant chronic
      bronchitis on neutrophil--macrophage index in tuberculous workers engaged into
      pneumoconiosis hazard industry. Increased more than 0.7, the index suggests
      unfavorable prognosis. Better prognosis requires mandatory examination of
      respiratory tract and sanation therapy.

PMID- 18051848
TI  - [Photometric method determining trifluoromethanesulfonic acid in work-place air].

PMID- 18051849
TI  - [An efficient tool for the construction of multiple-cistronic vectors: FMDV 2A].
AB  - Recently, cancer therapy with mutiple genes has been attached with great
      attention. However, at present there is no efficient tool to construct multiple
      cistrons. The large sizes and the imbalance in expression of most traditional
      tools, such as ribosome entry sites (IRESes),greatly block their wide employment
      in the construction of multiple cistronic gene therapy vectors. The self-cleaving
      peptide 2A from foot-and-mouth disease virus (FMDV) has a very small size, and
      more importantly, high cleavage activity in artifical bicistron, which bring new
      hope for mutiple genes therapy stategy. In this article, the characteristics and
      cleavage activities of FMDV 2A will be elucidated,and we further outline its
      applications in cancer gene therapy.

PMID- 18051850
TI  - [The function of glutathione/glutathione peroxidase system in the oxidative
      stress resistance systems of microbial cells].
AB  - The physiological roles of the glutathione(GSH)/glutathione peroxidase(GPx)
      system in protecting microbial cells against oxidative stress were reviewed. In
      eukaryotic model microbe Saccharomyces cerevisiae,this system is obligatory in
      maintaining the redox balance and defending the oxidative stress. However, the
      GSH/GPx system only conditionally exists in prokaryotes. Namely,for those
      prokaryote bacteria containing glutathione reductase and GPx, e.g. Haemophilus
      influenzae and Lactococcus lactis, by taking up GSH, they might develop a
      conditional GSH-dependent GPx reduction system, which conferred cells a stronger
      resistance against oxidative challenge.

PMID- 18051851
TI  - [The mechanism and efficiency affecting factor of cationic liposome
      transfection].
AB  - Cationic liposome is a greatly promising gene carrier. In this paper, the
      structure trait of cationic liposome was briefly introduced, the mechanism of
      cationic liposomes mediated gene delivery and the main influencing factor of
      transfection efficiency in the transfection process were discussed chiefly.

PMID- 18051852
TI  - [The basics of 14-3-3 protein family and research progress on therapeutic
      applications of 14-3-3 protein].
AB  - The 14-3-3 proteins comprise a family of highly conserved acidic protein with
      subunit molecular mass 28-33kD and are widely found in different eukaryotic
      cells. 14-3-3 proteins were the first polypeptides shown to have
      phosphoserine/threonine (pSer/Thr) binding properties which firmly established
      its importance in cell signaling. 14-3-3 proteins tend to form dimeric proteins
      to modulate protein-protein interactions. 14-3-3 proteins have been shown to
      contribute to the regulation of such crucial cellular processes as metabolism,
      signal transduction, cell cycle control, cell growth and differentiation,
      apotosis, protein trafficking, transcription, stress responses and malignant
      transformation. Many reports link 14-3-3 to disorders, particularly the
      neurological disorders and cancer. The 14-3-3 test has been used for the
      diagnosis of prion diseases. 14-3-3 could be exploited for therapeutic purposes.
      In this review, we discuss the structure, function of 14-3-3 protein and the
      related research progress in therapeutic applications.

PMID- 18051853
TI  - [Study on the atrazine-degrading genes in Arthrobacter sp. AG1].
AB  - Atrazine could be used as the sole carbon, nitrogen and energy sources for growth
      by strain Arthrobacter sp. AG1, and the atrazine-degrading genes of AG1 were
      found to be the combination of trzN, atzB and atzC. The atrazine chloride
      hydrolysase gene trzN was cloned by PCR amplification,whose sequence shared 99%
      identity with that of Norcardioides sp. C190. Two large plasmids were found in
      AG1,and trzN and atzB were confirmed to be localized on the larger plasmid pAG1
      by the method of southern hybridization. Subculture of AG1 in liquid LB for three
      generations, 34% of the subsequent cells were found to lose degrading activity,
      however, neither plasmid was lost. PCR amplification results showed that the
      mutants had only lost the trzN gene instead of atzB and atzC. It was deduced that
      mutation might be due to the trzN gene deletion from the plasmid. This study
      provided new evidence that atrazine metabolic genotypes were resulted from
      horizontal gene transfer between different bacteria under environmental selective
      pressure.

PMID- 18051854
TI  - [Selection and inhibitory effect analysis of siRNAs specific to ORF2-4 of porcine
      reproductive and respiratory syndrome virus].
AB  - RNA interference (RNAi) is a powerful tool in gene function research. In order to
      investigate the role of GP2, GP3 and GP4 of porcine reproductive and respiratory
      syndrome virus (PRRSV) in the viral replication, small interference RNAs (siRNAs)
      directed to ORF2, ORF3 and ORF4 were designed and 12 short hairpin RNA (shRNA)
      expression vectors were constructed (designed as 21,22,23,24,31,32,33,34,41,42,43
      and 44). Cells treated with shRNA expression vectors were infected by PRRSV. The
      effective shRNA expression vectors were selected by fluorescent quantatitive PCR
      (FQ-PCR). The virus titer of supernatant of the cells treated with effective
      shRNA expression vectors (23,24,31,34 and 41) were reduced by 184 to 4.65 folds
      compared with that of controls.

PMID- 18051855
TI  - [Rapid disruption of Bombyx mori nucleopolyhedrovirus orf60 by red recombination
      system].
AB  - BmNPV bacmid constructed recently and Red recombinant system were used to rapidly
      disrupted Bombyx monri nucleopolyhedrovirus (BmNPV) orf60 in Escherichia coli (E.
      coli) BW25113. BmNPV bacmid isolated from E. coli BmDH10Bac was electroporated
      into E. coli BW25113, which harbors plasmid pKD46 encoding lamda Red
      recombinase,to produce E. coli BW25113-Bac, which could be used for gene deletion
      of BmNPV. A linear fragment was amplified by PCR from plasmid pKD3 (containing a
      chloramphenicol acetyltransferase gene cat) using a pair of primers with length
      of 63bp,which had 45 bp homologous to the orf60 gene and 18bp homologous to cat
      sequences. The linear fragment was electroporated into E. coli BW25113-Bac and
      homologous recombination occurred between the linear fragment and orf60 with the
      help of lamda Red recombinase. Three specific primer pairs were used to confirm
      the replacement of orf60 by cat gene. Western blot analysis showed that orf60 was
      not expressed in BmN cells infected with knockout bacmid.

PMID- 18051856
TI  - [Infectious bovine rhinotracheitis viral gG expression and gG-ELISA development].
AB  - Taking the genome DNA of Infectious Bovine Rhinotracheitis Virus (IBRV) as the
      template, the gG gene was amplified with PCR and cloned into the T cloning vector
      pMD18-T. After being identified by restriction digestion and DNA sequencing, the
      insert was subcloned into the expression vector pGEX-KG. Sodium docecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot assay showed that
      this gene was expressed as both soluble form and inclusion body by the
      transformed E. coli BL21 strain (DE3). The fusion protein was purified and used
      as the coating antigen to develop the indirect Enzyme-Linked Immunosorbent Assay
      (ELISA). Comparison between this gG-ELISA and commercial IBRV gB-ELISA Kit
      (IDEXX) was made in the detection of 380 cow serum samples. The results
      demonstrated an agreement of 92%. By using this novel gG-ELISA, 1248 cow serum
      samples were tested and the average positive rate of IBRV antibodies for imported
      cows is 21.7%, while the positive rate ranged greatly from 0.0%-41.5% for Hubei
      local Chinese Black and White Dairy Cows.

PMID- 18051857
TI  - High-level expression of the Hcc domain of Clostridium botulinum neurotoxin
      serotype A in Escherichia coli and its immunogenicity as an antigen.
AB  - A completely synthetic gene encoding the He domain of Clostridium botulinum
      neurotoxin serotype A (AHc, 1287 bp, 429 aa, -50 kD) was constructed with
      oligonucleotides. After expressed in Escherichia coli, soluble product AHc was
      gained and verified by SDS-PAGE and Western blot analysis. The expressive level
      of recombinant AHc in E. coli was very high (36%-53% of soluble total proteins)
      and the purified yield was more than 30 mg/L by one-step purification. Then, the
      purified AHc was used to vaccinate Balb/c mice, which developed a strong and
      specific immune response as expected following administration of AHe protein via
      the subcutaneous route. Results from BoNT/A neutralization assay showed that the
      serum from mice vaccinated with AHc contained high titer protective antibody.
      These results showed that the soluble, stable and high-levelly expressive AHc not
      only could be produced by the prokaryotic expression system built in our lab, but
      also owned strong immunogenicity to prepare antitoxin for treatment and as sub
      unit candidate vaccine for prophylaxis against botulinum toxin serotype A.

PMID- 18051858
TI  - [Expression and analysis of recombinant pIL-18 in Pichia pastoris].
AB  - The porcine IL-18 gene was amplified from recombinant plasmid pGEM-IL-18 by PCR,
      then the pPIC9K-IL-18 of fusion expression vector was constructed by inserting IL
      18 fragment,and was transformed to GS115 by electroporation, multi-copy
      recombinant strains were screened by G418. The expression of recombinant fusion
      protein was induced by methanol, SDS-PAGE was used to analyze expression product,
      fusion protein was purified by Sephadex G-100 column, bioactivity of IL-18 was
      measured by MTT assays. Experiment results show fusion protein of pIL-18 secreted
      by GS115,expression reaches the secretion peak of 160 mg/L at 72 h. We have
      expressed and purified successfully the recombinant pIL-18 with obvious
      biological activity in Pichia pastoris.

PMID- 18051859
TI  - [Expression of human intestinal trefoil factor in Pichia pastoris and its
      biological activity on intestinal epithelium in vitro].
AB  - In order to produce relatively large amounts of recombinant human intestinal
      trefoil factor and assess its biological activity. The expression plasmid pPIC9
      hITF containing AOX1 promotor and the sequences of secreting signal peptides was
      transformed into the yeast cells. Then through selection, positive transformants
      were cultivated in fermentation basal salts medium in a 5L fermenter to obtain
      large amount product with low cost. The secreted peptides were then purified by a
      combination of ionic exchange chromatography and molecular sieve. To verify the
      product, electrospray mass spectrometry analyses was used to determine the
      structure of rhITF and Western Blotting was performed to test the immunological
      activity. Furthermore, the biological activity of the peptide was examined by
      experiments from cell to tissue. The nucleotide sequence of rhITF was the same as
      expected. With a 5-L fermenter, 253mg of hITF was isolated at the purity of 96%
      from 3.5 L of yeast fermentation broth. The expression level for recombinant
      human ITF in this yeast system was 73.33mg/L. In our study, we provided a way to
      gain a production among milligram to gram of recombinant human ITF by the use of
      a yeast expression system. As human ITF are difficult to purify in any
      significant amount from tissue extraction, the way described may become a
      valuable tool in obtaining pure peptide for further studies of trefoil peptide
      function.

PMID- 18051860
TI  - [Study on the characteristics of tissue expression of hormone sensitive lipase
      and triacylglycerol hydrolase in pigs].
AB  - The specific expression of TGH and HSL genes in different tissues of Bamei pig
      was investigated by RT-PCR and Western blot in this study. The result of RT-PCR
      showed that the expression of HSL could be detected in all these seven tissues
      examined, and which was higher expressed in fat, lower in heart, liver, lung,
      spleen and kidney. Expression of TGH gene could also be detected in seven
      tissues, and higher in liver and fat, lower in heart and kidney and lowest in
      spleen and lung. The result of Western blot showed that, HSL gene was highest
      expressed in epiploica fat and subcutaneous fat, higher in other tissues, but
      couldn' t be detected in kidney. Expression of TGH was detected in epiploica fat,
      subcutaneous fat, liver, lung and spleen, and highest in fat and liver, but it
      hadn't be found in heart and kidney. These results suggested that both HSL and
      TGH could be regulated by post-transcriptional, and their function was involved
      in different tissues.

PMID- 18051861
TI  - [Isolation and analysis of a high expression promoter in rice].
AB  - The expression of plant gene is controlled by its promoter. The isolation and the
      function analysis of promoter are important for studying the genetic engineering
      and the regulation expression of plant genes. In this paper, we cloned a
      promoter, 0s252, which was predicted to be highly expressed in the stem of rice
      from the EST database. After the construction of the Os252::GUS expression
      vector, it was transformed into rice. The integration of transgenes into
      transgenic rice genome was confirmed through PCR analysis. X-Gluc staining showed
      that Os252 can promote GUS gene expression in leaf, stem and matured seed. GUS
      enzyme activities driven by Os252 promoter in leaf and seed are about 190% and
      250% of that driven by the 35S promoter. Thus, the Os252 promoter can be applied
      for rice genetic engineering.

PMID- 18051862
TI  - [Construction of novel recombinant strain harboring glycerol dehydratase
      reactivating factor capable of producing 1,3-propanediol].
AB  - The dhaB gene encoding glycerol dehydratase and dhaG dhaF gene encoding glycerol
      dehydratase reactivating factor from Citrobacterfreundii were amplified by PCR.
      The temperature control expression vector pHsh harboring yqhD, dhaB, dhaG and
      dhaF gene was transformed into E. coli JM109 to yield the recombinant strain E.
      coli JM109 (pHsh-dhaB-dhaG-dhaF-yqhD). The results from SDS-PAGE analysis show
      that the recombinant product was consistent with the molecular weight predicted
      from gene sequence. The fermentation result show that the yield of 1,3
      propanediol was increased by 28% compared with E. coli JM109(pHsh-dhaB-yqhD).

PMID- 18051863
TI  - [Type III secretion study of popN- mutant of Pseudomonas aeruginosa and proteases
      degradation].
AB  - Pseudomonas aeruginosa is an important opportunistic human pathogen. It encodes
      many virulence factors and one of them is type III secretion system (TTSS).
      Effectors proteins can be delivered into host cells directly by this system,
      causing necrosis or apoptosis. popN gene is the first gene in the popN operon of
      TTSS gene cluster. To investigate its function, popN gene deletion mutant was
      generated in this study, and we found this mutant can secrete effectors proteins
      constitutively under non-inducting condition in DMEM medium containing serum. The
      results indicated that PopN is a negative regulator of the TTSS expression.
      However, no secreted effector proteins were detectable when the popN- mutant was
      grown in LB medium under non-inducting condition. To investigate the possible
      reasons, effects of growth status and protease (s) inhibitors on the TTSS were
      investigated. We present evidences that indicate protease mediated degradation of
      secreted effector proteins played a key role in the phenotypic inconsistency of
      popN- mutant.

PMID- 18051864
TI  - [Preparation of a novel telomerase inhibitory protein LPTS-L].
AB  - The gene for LPTS is originally cloned as a human liver-related putative tumor
      suppressor (LPTS) gene that encodes a full length protein of 328 amino acids
      (LPTS-L). LPTS-L is also identified as a telomerase inhibitor to regulate
      telomere length in the cells. To facilitate the functional and structural studies
      of LPTS-L protein, the cDNA for LPTS-L was cloned into the expression vector pET
      24 in frame to generate a recombinant plasmid pET-24-LPTS. The LPTS-L protein was
      expressed in E. coli BL21 solublely, and purified by Ni Sepharose affinity
      chromatography which, however, is not fit for large scale protein purification.
      The gene of LITS-L was then PCR amplified to remove the 6 x His tag, and cloned
      into pET-24a. The non-fusion protein of LPTS-L was expressed in E. coli B21, and
      purified by phosphocellulose P11 chromatography. The purity of LPTS-L protein was
      about 55% after that procedure,and arrived at 80% after second purification by
      Sephadex G-100 chromatography. Western Blotting analysis showed that the band
      reflects the specific binding of anti-LPTS antiserum against the purified LPTS-L
      protein. The TRAP assay was performed to detect the telomerase inhibitory
      activity of LPTS-L protein in vitro. It was observed that the purified LPTS-L
      inhibited the activity of telomerase greatly, similarly with that of LPTS-L
      protein purified by Ni Sepharose 4B. Our results suggest that phosphocellulose
      P11 plus Sephadex G-100 chromatography could substitute for Ni Sepharose 4B
      affinity chromatography for preparation of purified LPTS-L protein. Through this
      study, a technique for preparation of LPTS-L protein in a large scale is
      established.

PMID- 18051865
TI  - [Construction, fermentation and purification of high polymer spider dragline silk
      protein containing RGD peptide].
AB  - Spider silk is a natural protein fibroin with excellent character as it is light
      and tenacious. It has a wild potential applications in the biomedical field due
      to its good biocompatibility and degradation. Arginine-glycine-aspartic acid
      (RGD) is a highly conserved amino acid sequence of many adhesion protein.
      Biological materials binding with RGD peptide in the surface can promote cells
      adhesion, migration and proliferation. Our lab had constructed the 16 muhimers
      with the introduced RGD peptide codons which involve cell adhesion for the first
      time. It was found that the mechanical capability of the 16 mulimer protein was
      very limited because of the big gap in molecular weight with nature spider
      proteins when it was used to made biomaterial scaffold.In this paper,based on the
      16 multimers of the highly, repetitive sequence of spider dragline silk and with
      RGD peptide condons which has been constructed by our lab forestall, it was used
      to construct the 32 and 64 multimers sequence of spider dragline silk by the
      strategy of "head to tail". The 32 and 64 multimers were ligated into prokaryotic
      expression vector pET-30a, and then the B121 (DE3) pLysS. The fragments were in
      agreement with the desired through digestion, agarose gel electrophoresis
      respectively. By registration into the GenBank data-base, the serial numbers of
      DQ469929 and DQ837297 were gained respectively. The expression of recombinant
      protein was introduced by the addition of IPTG. SDS-PAGE analysis shows that the
      molecular weight of products expressed here are 102 kD and 196.6kD in agreement
      with the desired respectively. It was the first time for the high polymer spider
      dragline silk protein expressed in prokaryotic biology. Furthermore, a larger
      quantity of synthetical proteins with high density fermentation were searched
      after, and a suit of high efficient purification methods for 32 multimers protein
      were established.

PMID- 18051866
TI  - [Comparison of immune responses induced by recombinant attenuated Salmonella
      typhi carrying eukaryotic expression plasmid or prokaryotic expression plasmid of
      HCV core protein].
AB  - Hepatitis C virus (HCV) core protein is considered to be an attractive candidate
      for development of protective HCV vaccines. However, this protein may attenuate
      the induction of systemic immune responses due to its immunomodulatory
      properties. In this study, we constructed a HCV core gene-containing eukaryotic
      expression plamid pCI-C, and an in vivo-inducible prokaryotic expression plasmid
      pZW-C, and transformed the recombinant plasmids into an attenuated Salmonella
      typhimurium aroA strain SL7207. The resulting bacterial strains SL7207/pCI-C and
      SL7207/pZW-C were used to orally immunize BALB/c mice, and the immune responses
      specific to HCV core protein were assessed. Immunization with the recombinant
      bacteria SL7207/pCI-C led to a persistent drop in percentage of CD3 CD4 T cells,
      and induced a weak anti-core IgG production. Splenocytes from SL7207/pCI-C
      immunized mice developed a relatively weak proliferation response and inferior
      cytotoxic activity compared to those from the mice immunized with bacteria
      SL7207/pZW-C. Boost immunization with SL7207/ pCI-C yielded limited improvement
      in immune strength, while the boost with bacteria SL7207/pZW-C significantly
      enhanced the immune response. These results suggest that de novo synthesis of
      native HCV core protein may blunt the induction of immune responses. Attenuated
      S. typhimurium carrying HCV core protein could efficiently activate systemic
      cellular and humoral responses, and may be a promising strategy for the
      development of core-based HCV vaccines.

PMID- 18051867
TI  - [Proteomics analysis of fat body from silkworm (Bombyx mori)].
AB  - High resolution two-dimensional polyacrylamide gel electrophoresis, followed by
      computer-assisted analysis, was applied to investigate the fat body of silkworm,
      Bombyx mori. 722 spots were obtained by silver stain from 18 cm, pH 3-10 gel.
      Most of them were distributed in the area from 15 kD to 90 kD with pH 4 - 8. The
      matrix-assisted laser desorption ionization time of flight mass spectrometry were
      applied for identifying the major spots of the 2D map. A total of 41 spots were
      excised to identify by a combination of MALDI-TOF MS after digested with trypsin.
      The result showed among the 34 proteins identified, plenty of them were involved
      in metabolism and immunity. Additionally, Heat shock proteins, 30K proteins and
      Actin were also detected in the fat body of silkworm. The result will provide a
      useful tool for understanding the role of fat body in silkworm.

PMID- 18051868
TI  - [Expression of pectin lyase 1 from Aspergillus oryzae in Escherichia coli].
AB  - Pectin lyases from Aspergillus oryzae and Aspergillus niger are usually used for
      the production of traditional fermented foods, but these fungi produce less
      pectinases under natural conditions. The cDNA coding mature Pell (without signal
      peptide) was amplified from Aspergillus oryzae by RT-PCR. Pell cDNA was cloned
      into pET-28a ( + ) expression vector, then was transformed into E. coli Turner
      (DE3) plac I cells to express Pell with 6-His tag. For improving the efficiency
      of Pell expression in E. coli, the conditions of expressing the Pell in E. coli
      were optimized. E. coli Turner (DE3) plac I cells with pET-28a ( + )-pell was
      first cultivated at 37 degrees C, 220 r/min until OD600 reached about 0.8. Then,
      cultivation broth was added with 0.05-0.1 mmol/L IPTG and continuously incubated
      at 15 degrees C, at 170 r/min for 60 h for expressing of Pell. The recombinant
      expressed Pell activity could reach 400 u/mL medium, which is 4000-fold of Pell
      produced naturally by A. oryzae and superior than known recombinant amount of
      pectin lyases expressed in different fungi expression systems.

PMID- 18051869
TI  - [The influence of controlling redox potential on ethanol production by
      Saccharomyces cerevisiae].
AB  - Redox electrode was used to control redox potential at four different levels (-50
      mV, -100 mV, -150 mV, - 230mV) for the study of ethanol fermentation. The result
      showed that there was notably influence on the yield of ethanol, the formation of
      glycerol, the secretion of organic acid, biomass and the death of cell by
      controlling redox potential at different levels. For example: the biomass of ORP
      at -50 mV was 1.26, 1.86, 2.59 times higher than ORP at -100 mV, -150 mV, -230 mV
      respectively, the final glycerol concentration was 1.2, 1.1, 1.7 times higher but
      final ethanol concentration was 0.87, 0.49, 0.51 times lower compared to the
      latest three ORP control level. And take biomass, ethanol yield, glycerol
      concentration, and unconsumed glucose into consider, we get the conclusion that
      it is very favorable for ethanol fermentation by control ORP at 150 mV. So it
      give us a apocalypse that we can use redox electrode to control the ethanol
      fermentation exactly on bioreactor scale.

PMID- 18051870
TI  - [Potential use of the herbicide quizalofop-p-ethyl for eicosapentaenoic acid
      overproduction by the diatom Nitzschia laevis].
AB  - The diatom Nitzschia laevis is a good alternative source of eicosapentaenoic acid
      (EPA). Besides strategies for high cell density culture, EPA productivity may be
      further improved by herbicides. The effect of the herbicide quizalofop-p-ethyl on
      the growth and EPA production was studied in this paper. As the solvent of the
      herbicide, DMSO was proved to inhibit the growth and EPA production of N. laevis.
      The concentration of DMSO in the medium should not exceed 0.2%. Quizalofop-p
      ethyl could cause morphology damage to the N. laevis cells. With the increasing
      concentration of quizalofop-p-ethyl from 0 mmol/L to 0.4 mmol/L, the dry cell
      weight production decreased, while at the same time, the lipid content of the dry
      cell mass increased. When treated with 0.1 mmol/L quizalofop-p-ethyl, the EPA
      content increased from 3.00% to 3.58% (of dry cell weight, DW), and the
      proportion of EPA (20:5) in total fatty acids (TFA) increased from 25.15% to
      32.88% . These results indicated that the herbicide quizalofop-p-ethyl could
      stimulate the accumulation of EPA; therefore it might be useful for selecting
      algae colonies that overproduce EPA.

PMID- 18051871
TI  - [Purification of L-sorbose/L-sorbosne dehydrogenase from Ketogulonigenium vulgare
      and construction and selection of genomic library].
AB  - L-sorbose/L-sorbosone dehydrogenase from Ketogulonigenium vulgare S2 can
      transform L-sorbose to 2-KLG, which is widely used in production of Vitamin C. In
      order to obtain the engineering strain producing L-sorbose/L-sorbosone
      dehydrogenase and simplify the fermentation technology, firstly, this enzyme was
      purified by the methods of ammonium sulfate precipitation, DEAE Sepharose Fast
      Flow and Q Sepharose High Performance. Then, the purified L-sorbose/L-sorbosone
      dehydrogenase was injected to rabbit to obtain antibody. Next, the genomic
      library of Ketogulonigenium vulgare S2 was constructed by inserting the
      restriction fragments of chromatosomal DNA digested with Sau3A I into cosmid
      pKC505 vector digested by Hpa I and Pst I, which were packed with lamda phage
      package protein and transferred into E. coli DH5alpha in vitro. Finally, the
      positive strain K719# was selected from more than 12,000 clones via Dot-ELISA.
      Through the test of SDS-PAGE and thin layer chromatography, the results showed
      that the engineering strain K719# had the same biological activity as
      Ketogulonigenium vulgare S2 after adding coenzyme PQQ.

PMID- 18051872
TI  - [Study on the metabolism of Escherichia coli DH5alpha and its acetate-tolerant
      mutant DA19 based on key enzyme activity analysis].
AB  - The differences in metabolism in Escherichia coli DH5alpha and its acetate
      tolerant mutant DA19 were analyzed based on the activity of key enzymes involved
      in central metabolism when both strains were continuously cultured in nitrogen
      source-limited defined media. The activity of glucose-6-phosphate dehydrogenase
      (G6PDH) and isocitrate dehydrogenase (ICDH) in DA19 increased as compared with
      those in DH5alpha, while acetate kinase (ACK) and phosphofructosekinase (PFK)
      decreased. These indicated that more carbon flux of DA19 entered the
      phosphopentose pathway (PPP) and less entered the glycolytic (EMP) pathway and
      acetic acid production (Ack-Pta) pathway. Therefore, the differences in activity
      of key enzyme coincided with increased cell yield based on consumed glucose
      (Y(X/G)) and decreased production of acetic acid and pyruvate of DA19. G6PDH and
      ICDH in DH5alpha were up-regulated by addition of adenine, while ACK and PFK were
      down-regulated. On the other hand, adenine had little effect on those in DA19.
      The enzymes except PFK in both strains were down-regulated by sodium acetate,
      especially the activity of ICDH in DH5alpha. These results suggested changed flux
      of central metabolic pathways were also consistent with the changes of growth
      properties and byproducts formation.

PMID- 18051873
TI  - [Constitutive expression of human angiostatin in Pichia pastoris using glycerol
      as only carbon source].
AB  - Carbon source plays an important role in the constitutive expression of foreign
      proteins in Pichia pastoris. In present study, glucose , glycerol , methanol and
      oil acid, was used respectively as the only carbon source to constitutively
      express hAS in Pichia pastoris GS115 (pGAP9K-AS)in shaking flask. The result
      shows that oleic acid is the best (163 mg/L) compared with glycerol (83mg/L),
      glucose (76 mg/L)and methanol (57 mg/L). Since oleic acid is insoluble in water,
      glycerol was used as the carbon source in the high-density cell culture of GS115
      (pGAP9K-AS) in a 30 liter bioreactor and 169 mg/L of angiostatin was obtained
      after 48h of culture. The expressed angiostatin is immunologically active as
      shown by Western blotting. The recombinant hAS inhibits bFGF induced CAM
      angiogenesis and suppresses the growth of B16 melanoma in C57BL/6J mice. The
      tumor inhibition rate is 90% after 12 days of treatment. Statistics analysis
      revealed that the tumor volume difference of mice between the hAS group and PBS
      group is prominent (P < 0.01).

PMID- 18051874
TI  - [A Pichia pastoris with alpha-1, 6-mannosyltransferases deletion and its use in
      expression of HSA/GM-CSF chimera].
AB  - Yeast is a widely used host for recombinant protein expression. However,
      glycoproteins derived from yeast contain N-glycan of high mannose type and are
      usually hyperglycosylated. alpha-1,6-mannosyltransferases gene (och1) encodes the
      enzyme that initiates the first step of out-chain elongation of high mannose type
      N-glycan in yeast, which is different from that in human. So, a high efficient
      method to knockout target gene by two-step recombination was established and was
      used to delete och1. In the first recombinant, a plasmid with och1::ADE1 and ura3
      gene was linearized in the downstream of och1 and inserted to the och1 site of P.
      pastoris genome, where the upstream and downstream of och1 were duplicated. In
      the second recombinant, the duplicated fragments of och1 were exchanged and the
      och1 deletion strains were selected on the plates containing 5-FOA, but no
      adenine. Then the och1 deletion strain was applied to express an human serum
      albumin (HSA) granulocyte-macrophage colony-stimulating factor (GM-CSF) chimera.
      Different with the hyperglycosylated HSA/GM-CSF chimera expressed in wild type P.
      pastoris, the chimera expressed in the och1 deletion strain, contained smaller N
      glycan. The results suggested that the och1 mutant yeast may be more suitable for
      production of recombinant glycoproteins. And the och 1 deletion strain could be
      used for further re-engineering to produce complex human glycoproteins.

PMID- 18051875
TI  - [Producing recombinant adenovirus encoding green fluorescent protein (Ad-GFP) by
      suspension cultured HEK-293 N3S cells].
AB  - Adenovirus vectors are one of the most promising gene transfer systems. They are
      of great value for gene therapy because these vectors achieve temporal high-level
      transgene expression and high gene transfer efficiency. To meet increasing needs
      of adenovirus vectors for gene therapy programs, parallel development of
      efficient, scalable and reproducible production processes is required. Perfusion
      cultivation of 293 cells is one of the most commonly used methods to produce
      adenovirus vectors and it is suitable for industrialized production specially.
      Experimental studies had been carried out to produce recombinant adenovirus
      containing the green fluorescent protein gene (Ad-GFP) by perfusion cultivation
      of HEK-293 N3S cells in a 5L stirring bioreactors. Perfusion rate was 1-2
      volume/day. To infect the 293 N3S cells with Ad-GFP at the density of (2-4) x
      10(6) cells/ ml. The time of collecting cells was 48 hours post infection. After
      three rounds of freeze/thaw and centrifugation, the crude viral lysates were
      stored at--80 degrees C until use. Then to get the Ad-GFP products by 2 x CsCl
      gradient purification. The purity of the products was determined by the A260/A280
      ratio and a high performance liquid chromatography (HPLC) assay. The infective
      titer was determined by a TCID50 assay. The culture term was 10-12 days. The
      infectious titer, the number of virus particle and the ratio of infectious titer
      to virus particle for the product were 1.0 x 10(11) IU/mL, 1.68 x 10(12) VP/mL
      and 6.0% IU/VP respectively. The A260/A280 ratio was 1.33, and the purity
      determined by HPLC was 99.2%. The cell specific productivity was around 1000
      IU/cell. By perfusion cultivation of 293 N3S cells in a 5L stirring bioreactors,
      we established the production process for Ad-GFP, which paves a way to produce
      other recombinant adenovirus for gene therapy.

PMID- 18051876
TI  - [Study of target pegylated recombinant mutant human granulocyte colony
      stimulating factor].
AB  - Recombinant mutant human granulocyte colony stimulating factor (rmhG-CSF) was
      pegylated, purified and characterized. rhG-CSF was mutated in position
      1,3,4,5,17, and cysteine was added in C-terminal. rmhG-CSF was pegylated by PEG
      Mal 20000 and separated by ion-exchange chromatography, gel filtration
      chromatography. Analysis of SDS-PAGE showed thar the purity of the separated PEG
      rmhG-CSF was greater than 95%. and in intro and in vivo bioactivity study showed
      that target modified PEG-rmhG-CSF kept full bioactivity which was better than
      traditional pegylation method, and longer half-life was proved in mice.

PMID- 18051877
TI  - [The oral immune efficacy of recombinant lactobacillus casei expressing CSFV E290
      peptide and it elicited specific CTL response].
AB  - The gene encoding classical swine fever virus (CSFV) T cell epitope E290 peptide
      was synthesized by PCR, cloned into the expression vector pPG-VP2 and named pPG
      VP2-E290. The recombinant plasmid was electrotransformed into Lactobacillus casei
      393 generating pPG-VP2-E290/L. casei 393. Specific anti-CSFV E290 peptide
      immunoglobulin G (IgG) antibody was detected by indirect ELISA in the serum of
      BALB/c mice and rabbits immunized with recombinant strain by oral administration.
      The CTL of E290 was analyzed with lymphocytes taken from the immunized mice, and
      the immunized rabbits were attacked with CSFV to validate the protective function
      of E290 antibody induced. RESULT: The recombinant expression system constructed
      with L. casei 393 in this study show a good immunization property and could
      elicit the mice and rabbits to produce high anti-E290 antibody levels.
      Furthermore, E290 peptide antibody could elicit specific CTL response, and
      restrain attack of CSFV to rabbits.

PMID- 18051878
TI  - [Effects of short-term continuous shear stress on cells growth and recovery of
      Laminaria japonica gametophytic cells in photobioreactor].
AB  - Laminaria japonica gametophytic cells were cultivated in a photobioreactor under
      continuous shear stress (0-1000 r/min) in 60 hours and the following static
      cultivation within 23.5 days. The content of chlorophyll a reached the maximum
      value of 2.36 mg/L at the end of continuous shear stress when the agitation speed
      was 90 r/min, while the chlorophyll a (chl a) concentration decreased quickly and
      nitrogen and phosphorus were released under high shear force (270-1000 r/min).
      The cell injury ratio at 1000r/min was as 18 times as that of the control. During
      the recovery course, gametophytic cells showed themselves distinct recovery
      capability at all agitation speeds. Furthermore, the content of chl a is a more
      exact index as biomass than dry cells weight (DCW). Besides cell injury ratio,
      the liberation of phosphorus demonstrates the cells injury.

PMID- 18051879
TI  - [Preparation of metal chelate affinity chromatographic medium and its application
      in the purification of 6 x histidine-tagged protein].
AB  - Using Sepharose CL-6B as support, 3-Chloro-1, 2-epoxypropane as activated agent,
      carboxymethylated aspartate (CM-Asp) as chelating ligand, A chelate affinity
      chromatographic medium based on Co2+, named Co-CM-Asp-Sepharose, was prepared and
      used to purify 6 x His-tagged fusion proteins. The amount of Co-CM-Asp-Sepharose
      reacted with 200 microL of lysate, the incubation time, wash condition and the
      imidazole concentration in the elution buffer were optimized. The purification
      results using Co-CM-Asp-Sepharose and Ni-NTA-Agarose (product of Qiagen) were
      compared. The CD155D1 fusion protein was also purified from 5mL of lysate and the
      amount of protein was determined by Bradford method. The results show that 60
      microL of Co-CM-Asp-Sepharose (50% suspension) was suitable for the protein
      purification from 200 microL of lysate, the optimal incubation time of medium and
      lysate was 30 min, the optimal imidazole concentration in the eluting buffer was
      200 mmol/L, and 200 microg of fusion protein was obtained. In a big scale
      experiment, 4.6 mg of fusion protein was obtained from 5 mL of lysate using 1.5
      mL of Co-CM-Asp-Sepharose (50% suspension). Compared with Ni-NTA-Agarose, the Co
      CM-Asp-Sepharose medium exhibits higher selectivity and the protein possesses
      higher purity.

PMID- 18051880
TI  - [Eukaryonization of T7 RNA polymerase prokaryotic expression system and
      development of its couple expression system].
AB  - To make transcription of the target gene be driven by T7 RNA polymerase (T7 RNAP)
      in the eukaryotic cells, and the transcripts be CAP-independent translated.
      Firstly, the T7 RNAP was introduced into eukaryotic cells by two methods: (1) the
      BHK-21 cells were contransfected by the plasmid expressing T7 RNAP and pIERS-EGFP
      ET vector; (2) by transfection of the cell line stably expressing T7 RNAP. The
      internal ribosome entry site (IRES) element from FMDV was cloned into the
      downstream of the T7 promoter sequence of the prokaryotic expressing vector pET
      40a-c (+), resulted in the plasmid would express the transcripts carrying the
      IERS element at its 5' end. The enhanced green fluorescent protein (EGFP) gene
      was cloned into the downstream of the IERS element, resulted in plasmid pIERS
      EGFP-ET. Then, the two kinds of cells expressing T7 RANP were transfected by
      pIERS-EGFP-ET. The green fluorescence in the transfected cells was observed under
      a fluorescence microscope equipped with a video documentation system. And the
      expressional efficiency was analyzed with flow cytometry (FCM). The results show
      that the IRES element from FMDV has the role of initiating CAP-independent
      translation, and lay foundation for researching function of the element and
      interrelated proteins. It would be potential for expressing target gene by the T7
      RNAP couple expression system.

PMID- 18051881
TI  - [Research of real-time fluorescent PCR in the rapid differential detection of H5,
      H9, H7 subtype avian influenza inactivated vaccines].
AB  - Specific primers and TaqMan MGB probes were designed with Primer Express 2.0
      software according to the conserved region of the H5, H9, H7 subtype AIV
      hemagglutinin gene to make research of real-time fluorescent one-step PCR in the
      differential detection of H5, H9, H7 subtype avian influenza inactivated
      vaccines. The result showed that the method was specific and reproducible. No
      cross-reaction was discovered with other avian disease vaccines. Real-time
      fluorescent PCR provided a specific, sensitive, rapid and convenient method for
      the subtype identification of avian influenza inactivated vaccines.

PMID- 18051882
TI  - [A novel system for producing lentiviral vectors].
AB  - The aim was to develop a cell culture system capable of producing high titer
      lentiviral vector stocks with recombinant vaccinia viruses as helpers. BHK21 was
      co-transfected by three main plasmids containing the transducing plasmid pVECRNA,
      the packaging plasmid pGAGPOL and the envelop plasmid pVSVG, and thereafter
      infected with the vaccinia vTF-3 containing bacteriophage T7 RNA polymerase gene
      using Lipofectamine2000. After 4 days incubation, the culture supernatant of
      lentiviral vectors was collected and judged by RT-PCR and the Western blot, the
      results showed that lentiviral vectors were found in the culture supernatant;
      approximately (11.71 +/- 0.80) x 10(11) copies of lentiviral vector RNA were
      present per mL of cell culture supernatant, as detected by Real-time PCR; the
      vector stocks with titers was up to (1.3 +/- 0.18) x 10(8) tu/mL, as detected by
      flow cytometry , which is one order of magnitude higher than the output of
      classical manufacture system. These results suggest that the new
      poxviral/lentiviral hybrid system for efficient lentiviral vector production was
      initially established. It provides the basis for the future development of
      industrial application.

PMID- 18051883
TI  - [Establishment of indirect ELISA diagnose based on the VP1 structural protein of
      foot-and-mouth disease virus (FMDV) in pigs].
AB  - The complete gene encoding the structural protein of FMDV(VP1) was subcloned into
      expression vector pPROex-HT, resulting in the fusion expression plasmid pPROexHT
      VP1. After transformed into E. coli BL21(DE3) and induced by IPTG, the fusion
      protein was expressed in high level. Western blot was performed to confirm that
      the expressed fusion protein could specifically react with antiserum against
      FMDV. Based on the fusion protein further purified, a novel indirect ELISA (VP1
      ELISA) was developed to detect FMDV antibody in pigs. Comparison between VPl
      ELISA and the government standard kit (liquid phase block ELISA) showed the two
      methods had 96.25 percent agreement by detecting 80 serum samples, indicating
      that the indirect VP1-ELISA was specific and sensitive.

PMID- 18051884
TI  - [Studies on seeds germination and seedlings growth of Notopterygium incisum].
AB  - OBJECTIVE: To investigate the appropriate culture medium, process of seeds
      germination and seedlings growth, and optical measures for seedling management of
      Notopterygium incisum. METHOD: Germination time and duration, germination
      potential and germination ratio were determined through controlled temperature,
      photoperiod, culture medium and seedling depth in illumination incubators.
      RESULT: The appropriate temperature was 15 degrees C, and the most suitable
      culture medium was A6 (mixture of sawdust, vermiculite, charcoal, and perliet),
      and the most suitable semination depth is 1-1.5 cm. CONCLUSION: High-qualified
      seedlings can be germinated through the dormancy-broken seeds, and soil and other
      culture mediums with high organic matter content and loosing texture are suitable
      for germination and seedlings raising of N. incisum.

PMID- 18051885
TI  - [Establishment of chromatographic fingerprint and quality assessment on Sichuan
      native medicinal plant Alisma plantago-aquatica].
AB  - OBJECTIVE: To establish chromatographic fingerprint of Sichuan native medicinal
      plant Alisma plantago-aquatica by RP-HPLC for the quality control. METHOD: The
      gradient elution mode was applied in chromatographic separation, and data were
      analyzed by "Computer Aided Similarity Evaluation" software to compare the
      quality of A. plantago-aquatica samples from different habitats. RESULT: The HPLC
      chromatographic fingerprinting of A. plantago-aquatica with 26 characteristic
      peaks was established from 17 lots of A. plantago-aquatica samples, peak 16 and
      22 were identified as 24-acetyl alisol A and 23-acetyl alisol B, respectively.
      CONCLUSION: The chromatographic fingerprinting of A. plantago-aquatica with high
      specificity can be used to control its quality and assure lot to lot consistency.
      The RP-HPLC fingerprint method is repeatable, feasible in analysis of A. plantago
      aquatica.

PMID- 18051886
TI  - [Study on conditions of seed germination of Cistanche].
AB  - OBJECTIVE: To study the effect of fluridone concentration, stimulating period,
      temperature and salt on the seed germination of three species of Cistanche.
      METHOD: The seeds were cultured in Petri dish, and the germination percentage was
      counted. RESULT: The highest germination percentage was observed in Cistanche
      tubulosa, C. deserticola, C. sala seeds pre-treated by 0.1 mg x L(-1) fluridone
      for 24-29 h. The optimal temperature for the seeds germination of three species
      of Cistanche was at 20-30 degrees C, and the seeds did not germinate at sub-or
      supraoptimal temperatures (5 and 35 degrees C). The salt tolerance of C. sala
      seeds was strong, and the critical value of NaCl concentration was 0.04 mol x L(
      1). By contrast, C. tubulosa and C. deserticola seeds were more sensitive to the
      salt stress, the critical value of NaCl concentration was 0.02 mol x L(-1).
      CONCLUSION: The optimal germination condition and the method of testing
      germination percentage of three species of Cistanche seeds are as follow: the
      seeds are pre-treated by 0.1 mg x L(-1) fluridone for 24 h and then cultured at
      20-30 degrees C in salt solution which concentration is lower than 0.02 mol x L(
      1).

PMID- 18051888
TI  - [SEM observation on leaf epidermis of different Ephedra species].
AB  - OBJECTIVE: Characters of stem epidermis, leaf epidermis and stoma could be used
      as important microcosmic morphological characteristic when inheritance trend is
      studied in Ephedra breeding and identification. METHOD: The stomatic density,
      stoma major axis and mimor axis, stomatic morphylogy, characters of leaf and stem
      epidermis of 6 Ephedra plants' stems were examined by SEM. RESULT: The stomatic
      density and characteristic of leaf epidermis and stem epidermis in six Ephedra
      species was differenc, there were no obvious morphological differences in stoma
      shape and size. The guard cells were covered with heavy cuticle and sunken
      stomata, which were the typical characteristics of xerophytes. The stomas of leaf
      lower epidermis were oblong or hexagon, but the stomas of steam epidermis were
      narrowed-oblong or dumbbell-shape, they all belonged to anomalous type.
      CONCLUSION: The stoma type and characters of Ephedra plants is stable and
      conservative, there was no obvious morphological differences in stoma shape and
      size between species, so it is difficult to distinguish different species by the
      variance of stomas, but that can be applyed to distinguish Ephedra from others at
      plant taxonomy.

PMID- 18051887
TI  - [Observation on gametophyte development of Cibotium barometz].
AB  - OBJECTIVE: To observe the spores germinating process of Cibotium barometz, and
      understand the growth principle provided for experience for indoor culturing and
      further research. METHOD: The spores of C. barometz were cultured both in
      inorganic medium and in the soil from original habitat, and the whole process of
      spores germination and the development of gametophytic were observed under
      microscope. RESULT: The spores germinated about 1-2 weeks after being sowed, and
      the type of germination belonged to Vittaria-type. The prothallial plates formed
      in 25 days after being sowed, while hairs developed after the formation of the
      prothallial plate. The gametophyte formed about 40 days after being sowed. But
      the type of mature prothalli was cordate. The antheridia formed in 60 days after
      inoculation, while the archegonia developed in 10 days after the formation of
      antheridia. CONCLUSION: Soil based indoor culturing of C. barometz spores is
      practical and can be used for cultivation of C. barometz.

PMID- 18051889
TI  - [Research on quality of Epimedium extract in market].
AB  - OBJECTIVE: To review the quality of Epimedium extract in the market. METHOD: The
      contents of icariin, epimedin C, sagittatoside B and total flavonoids in
      Epimedium extracts sold in the market were assayed by the methods of HPLC and UV
      respectively. HPLC fingerprintings were obtained at the same time. RESULT: The
      contents of icariin in most of the extracts are closely similar with the ones
      labeled by the companies. 3 type chromatograms were classified in all the HPLC
      fingerprintings, and were corresponded with their raw materials. The contents of
      epimedin C, sagittatoside B and total flavonoids were different in the samples
      with the same content of icariin. CONCLUSION: We can primarily confirm the origin
      of raw materials by comparing the HPLC fingerprinting of extracts with the ones
      of materials. The difference of extracts quality mainly comes from the difference
      of materials. So we suggest that Epimedium extract product should be labeled the
      origin of materials, and assayed with more compound contents, to ensure the
      quality stabilization.

PMID- 18051890
TI  - [Study on dynamical changes of Ginkgo biloba resources in Pizhou city of Jiangsu
      Province base on RS and GIS].
AB  - OBJECTIVE: To analyse the dynamical changes of the Ginkgo biloba's resources from
      2001 to 2006, in Pizhou city, Jiangshu province by useing spatial analytical
      function of GIS and RS technology. METHOD: Use the GIS and RS technology,
      extracted the information of G. biloba by scientific investigation, researched
      the spatial distribution and dynamical changes of G. biloba based on landsat 5
      TM: the Apr. 3rd, 2001; Jan. 16th, 2005; July 30th, 2006. RESULT: Ginkgo biloba's
      resource was 1.61 x 10(5) hm2 in 2001, 1.84 x 10(5) hm2 in 2005, 1.88 x 10(5) hm2
      in 2006. CONCLUSION: Ginkgo biloba's resource rised from 1.61 x 10(5) hm2 to 1.88
      x 10(5) hm2 from 2001 to 2006, showed the gradually rise.

PMID- 18051891
TI  - [RAPD analysis on genetic relationship among varieties of Rehmannia glutinosa].
AB  - OBJECTIVE: To define the genetic relationship and other genetic characters of
      different varieties of Rehmannia glutinosa. METHOD: RAPD reactions were conducted
      on total 54 samples from 16 varieties and 2 populations of R. glutinosa. The data
      were analyzed by Phylips, Popgene and Arlequin software. RESULT: The majority
      rule consensus tree defined the 54 samples to 3 groups. Population genetics
      analysis and AMOVA showed that the genetic diversity among varieties/populations
      much greater than that within varieties/populations, but within group II the
      genetic diversity among varieties was similar to that within varieties.
      CONCLUSION: Due to the long-time asexual propagation of R. glutinosa, some
      genetic differentiation has been accumulated and fixed within the species. It was
      shown that the genetic distance between wild population and cultivated varieties
      was greater than the genetic distance among cultivated varieties. The wild
      resource of the plant should be paid more attention and studies.

PMID- 18051892
TI  - [Studies on cutaneous permeation in vitro of Kushen recipe gel].
AB  - OBJECTIVE: To establish a suitable dosage form for a traditional anti-anaphylaxis
      Chinese medicine of Kushen recipe, and investigate the effect of cutaneous
      permeation in vitro of the recipe. METHOD: Techniques of extracting with ethanol
      and purifying with absorbent resin to obtain alkaloids from Kushen recipe were
      adopted, while volatile oil was extracted by steam distillation. The extraction
      was made to gel. The skin from SD rats' abdomen was used as permeability
      barriers. Then effects of permeation of the aqueous extraction, the purifying
      extraction and the gel were compared by Valia-Chien and Franz diffusion cell
      method. HPLC was utilized to quantitate the alkaloids in permeating liquid.
      RESULT: In view of the permeation cumulation quantity, the permeation velocity
      and the lag time of the four kinds of alkaloids, the effect of permeation of
      purifying extraction was better than the aqueous extraction, and the purifying
      extraction gel surpassed both the aqueous extraction and the purifying
      extraction. CONCLUSION: It was certified that the purifying extraction gel had
      improved the effect of cutaneous permeation of alkaloids, and it is the befitting
      dosage form for Kushen recipe to treat anaphylaxis disease in skin.

PMID- 18051893
TI  - [Freeze-drying of oleanolic acid-loaded nanosuspensions].
AB  - OBJECTIVE: Several cryoprotectants were employed to study the protective effect
      on the freeze-drying process of the oleanolic acid-loaded nanosuspensions (OLA
      LS) in order to select the optimum formulation. METHOD: The protective effect was
      evaluated by measuring the mean particle size of samples before and after freeze
      drying process. RESULT: Sucrose with the concentration of 10% was selected as the
      optimum cryoprotectant. The average size of excellent sample was 236.3 nm (versus
      211.2 nm of fresh one), and a much higher polydispersity index of 0.242 (versus
      0.180). CONCLUSION: The optimum lyophilized powder could be obtained with
      suitable type of cryoprotectant with appropriate concentration and proper freeze
      drying conditions.

PMID- 18051894
TI  - [Cutaneous permeation comparison of Kechuan acupoint patch and power].
AB  - OBJECTIVE: To compare the cutaneous permeation of Kechuan acupoint patch and
      power, and evaluate the possibility of dosage form reform of Kechuan recipe.
      METHOD: Take the Eugend and Ephedrine as the indexes, HPLC was employed to
      determine their contents, the pond with Franz diffusion were used to measured the
      cutaneous. RESULT: The permeation of Patch matched with Higuchi Equation. Take
      Eugend as the index, the permeation rate of total of Patch is 2.319 and 1.738
      times of the powder, and 1.784 and 1.215 times of the powder with the Ephedrineas
      as index. CONCLUSION: The permeation rate of Kechuan acupoint patch was more
      rapid than the powder. Moreover, the total quantity of permeation of patch was
      also more than the powder.

PMID- 18051895
TI  - [Investigation on one-pot extraction of active ingredient group from Yupingfeng
      powder by HPLC].
AB  - The extraction of active ingredient group, i.e., prim-o-glucosylcimifugin,
      astragaloside, and 5-o-methylvisammiosode from Yupingfeng powder with one-pot
      method was studied in this work. A HPLC method was used to determine the content
      of each active constituent mentioned above in the extract. The influences of
      extraction temperature, time, volume percent of ethanol in water and its amount
      added on the content and yield of active ingredient group were investigated by
      orthogonal test. The experimental results showed that the optimized extraction
      conditions were as follows: 1g of Yupingfeng powder was one-pot extracted for 4
      hours at 80 degrees C with 90% ethanol as solvent, and the yield and content of
      active ingredient group were 0.16%, 0.53% respectively. The active ingredient
      group in Yupingfeng powder could be effectively one-pot extracted under the
      conditions above.

PMID- 18051896
TI  - [Simultaneous determination of 5 active components in Fructus Cnidii by HPLC].
AB  - OBJECTIVE: To develop an RP-HPLC method for simultaneous determination of 5
      constituents in Fructus Cnidii. METHOD: Analysis was performed on an Alltech C18
      (4.6 mm x 250 mm, 5 microm) column. The mobile phases were acetonitrile water and
      acetic acid with gradient elution. The flow rate was 1 mL x min(-1). The
      monitoring wavelength was 325 nm and 245 nm. The column temperature was 40
      degrees C. RESULT: The linear response ranges were 1-20 microg x mL(-1) (r =
      0.999 9) for xanthotoxin, 1-20 microg x mL(-1) (r = 0.999 9) for isopimpinellin,
      11-20 microg x mL(-1) (r = 0.999 8) for bergapten, 100-1 200 microg x mL(-1) (r =
      0.999 7) for imperatorin, 100-2 000 microg x mL(-1) (r = 0.999 9) for osthole.
      The average recoveries were all above 95%. CONCLUSION: The method is simple,
      sensitive and accurate with good reproducibility.

PMID- 18051898
TI  - [Studies on triterpenoid constituents in leaf of Ilex pernyi].
AB  - OBJECTIVE: To investigate the chemical constituents of Ilex pernyi. METHOD: The
      chemical constituents were isolated by various column chromatographic methods.
      The structures were identified by spectral data. RESULT: Eight triterpenoid
      compounds were isolated and identified as ursolic acid (1), lupeol (2), alpha
      amyrin (3), uvaol (4), 3beta-hydroxyurs-11-ene-13beta-olide (5), pomolic acid
      (6), lup-20 (29)-ene-3beta, 24-diol (7), 3beta, 23-dihydroxy-urs-12-en-28-oic
      acid (8). CONCLUSION: The eight compounds were obtained from this plant for the
      first time.

PMID- 18051897
TI  - [Studies on polyphenolic chemical constitutents from root of Salvia yunnansis].
AB  - OBJECTIVE: To study the chemical constituents in the root of Salvia yunnansis.
      METHOD: Compounds were isolated and purified by Diaion HP20, Sephadex LH - 20,
      ODS chromatography. Their structures were determined by spectral analysis and
      chemical evidence. RESULT: Twelve compounds were isolated and identified from the
      root of S. yunnansis protocatechaldehyde (1), caffeic acid (2), ferulic acid (3),
      rosmarinic acid (4), salvianolic acid A (5), salvianolic acid C (6),
      lithospermicacid (7), lithospermicacid B (8), 9'-methyl lithospermate B (9), 9"'
      methyl lithospermate B (10), 9',9'''-dimethyl lithospermate B (11), 9'-ethyl
      lithospermate B (12). CONCLUSION: The compounds 1, 2, 3, 5, 6, 9, 10, 11 and 12
      were first isolated from S. yunnanensis.

PMID- 18051899
TI  - [Studies on chemical constituents from root of Actinidia macrosperma].
AB  - OBJECTIVE: To study the chemical constituents of root of Actinidia macrosperma.
      METHOD: Chromatographic methods were used to isolate compounds from A.
      macrosperma and spectroscopic methods were used to identify the structures of the
      isolated compounds. RESULT: Eight compounds were obtained and identified as 12
      oleanene-2alpha, 3alpha, 24-triol (1), isotachioside (2), asiatic acid (3),
      catechin (4), epicatechin (5), ursolic acid (6), beta-daucosterol (7), beta
      sitosterol (8). CONCLUSION: All these compounds were isolated from this plant for
      the first time, compound 1, 2 were obtained from this genus for the first time.

PMID- 18051900
TI  - [Studies on chemical constituents from root of Cynanchum atratum].
AB  - OBJECTIVE: To study the chemical constituents from the roots and rhizome of
      Cynanchum atratum. METHOD: The chemical constituents were isolated and repeatedly
      purified by silica gel chromatography and the structures were elucidated by the
      NMR spectra and physicochemical properties. RESULT: Twelve compounds were
      obtained and nine of them were identified as 2, 4-dihyroxyacetophe none (1), 2, 6
      dihyroxyacetophenone (2), 4-hydroxybenzenemethanol (3), benzoic acid (4), beta
      amyrin acetate (5), palmitic acid (6), beta-sitosterol (7), beta-daucosterol (8),
      glaucogenin C-3-O-alpha-D-oleandropyranosyl-(1 --> 4)-beta-D-digitoxopyranosyl-(1
      -->4)-alpha-D-oleandropyranoside (9). CONCLUSION: Seven compounds were obtained
      from C. atratum for the first time.

PMID- 18051901
TI  - [Study on variation of actinoside C in leaves of Actinidia kolomikta with
      different growth periods by RP-HPLC].
AB  - OBJECTIVE: To determine actinoside C in the leaves of Actinidia kolomikta with
      different growth periods. METHOD: The separation was performed at 25 degrees C on
      ZORBAX Extend C18 column (4.6 mm x 250 mm, 5 microm), using amixture of methanol
      and water (51:49) as a mobile phase. The flow rate was 1.2 mL x min(-1), and the
      wavelength for measurement was 267 nm. RESULT: The results showed that the
      contents of actinoside C in the leaves of A. kolomikta were variety in different
      growth periods. Actinoside C could reach its highest content in the middle ten
      days of June, then the content would decrease in the middle ten days of July
      slightly, it could reach their lowest content in the middle ten days of August.
      CONCLUSION: The optimal collective date for A. kolomikta are in the middle ten
      days of June.

PMID- 18051902
TI  - [Determination of macrozamin in Rhizoma Heterosmilacis Japonicae by RP-HPLC].
AB  - OBJECTIVE: To develop a RP-HPLC method for the determination of the content of
      macrozamin in Rhizoma Heterosmilacis Japonicae. METHOD: A Century C18 AQ column
      (4.6 mm x 250 mm, 5 microm) was used with the mobile phase consisted of water
      (4:96). The flow rate was 1.0 mL x min(-1). The detection wavelength was set at
      215 nm, and the column temperature was 35 degrees C. RESULT: The calibration
      curve was linear (r = 0.999 8) in the range of 19.12 - 382.4 microg x mL(-1) for
      macrozamin, the average recovery of the method was 99.5%, with RSD 2.1% (n = 9).
      CONCLUSION: This method can be used for the quality study of Rhizoma
      Heterosmilacis Japonicae.

PMID- 18051903
TI  - [Effects of salvianolic acid B on cerebral energy charge and activity of ATPase
      in mice with cerebral ischemia].
AB  - OBJECTIVE: To observe the effect of salvianolic acid B (SalB) on high energy
      phosphate and activity of ATPase of cerebral ischemia in mice, and to study the
      role of SalB on hydrocephalus further. METHOD: NIH mice were divided into four
      groups randomly: Sham-operated group, cerebral ischemia group, SalB-treated group
      and Nimodipine (Nim)-collated group. In Sal B-treated group, mice were injected
      with SalB (22.5 mg x kg(-1)) in vena caudalis at 30 min before the experiment. In
      Nim-collated group, Nim (0.03 mg x kg(-1)) was injected into tail vein at the
      same time, while the mice in Sham-operated group and cerebral ischemia group were
      injected the same volume normal saline. The acute cerebral ischemia model was
      established by ligating bilateral common carotid arteries for 30 min in mice,
      then the mice were killed and the content of adenosine triphosphate (ATP),
      adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphocreatine (PCr)
      were observed, and the cerebral energy charge (EC) was computed. At the same
      time, activity of Na(+) -K(+) -ATPase and Ca2(+) -ATPase, content of water in
      brain tissue were measured. RESULT: Compared with cerebral ischemia group, EC and
      content of ATP, ADP, PCr in SalB-treated group heightened evidently (P < 0.01).
      Moreover, activity of Na(+)-K+ ATPase and Ca2+ ATPase in SalB-treated group had a
      remarkable increase (P < 0.01). But the content of water in brain tissue
      decreased markedly (P < 0.05). CONCLUSION: The mechanism that SalB can relieve
      content of water in brain tissue of cerebral ischemia in mice, may be associated
      with improving the content of high-energy phosphoric acid compounds and enhancing
      the activity of ATPase.

PMID- 18051904
TI  - [Effect on mouse S180 MDR tumour cell expression correlated factorial matter by
      70% ethanol with Huanglian Jiedu Tang].
AB  - OBJECTIVE: To observe the effect on P170, LRP, TOPO II of S180 tumour MDR mice
      for matter by 70% ethanol with Huanglian Jiedu Tang, and then discuss the
      molecular biology base for clinic. METHOD: 18-22 gramme mice were divided into
      four groups for normal S180 tumour cell group, matter by 70% ethanol with
      Huanglian Jiede Tang 100 mg x kg(-1) and 50 mg x kg(-1) in random. Each mouse was
      given S180 cell 0.2 mL by celiac, and after 24 hours give cisplatin for Injective
      3 mg x kg(-1), ip, once a week. And give cyclophosphamide and 5-FU 3 mg x kg(-1),
      ig, once every day. After 15 days, collect lively mice ascites and give it for
      onefold normal mice. And then repeat before process. At the same time, every
      group was given corresponding medicine for 0.2 mL x 10 g(-1). The normal group
      and the model group were given the same cubage water, all together fore weeks. At
      last observd the P170, LRP, TOPO II by flow cytometry. RESULT: Matter by 70%
      ethanol with Huanglian Jiedu Tang could obviously reduce the express of P170 and
      LRP, and the activiation of TOPO II. CONCLUSION: Matter by 70% ethanol with
      Huanglian Jiedu Tang can intervene the ocurrence of the multi-drug resistance of
      tumour cells by regulating the biology gene.

PMID- 18051905
TI  - [Effects of Dioscorea septemloba on bone metabolism in ovariectomized rats].
AB  - OBJECTIVE: To investigate the effects of the decoction of Rhizoma Dioscorea
      septemlobae (RD) on the bone metabolism in ovariectomized rats. METHOD: Thirty
      female, 3-month-old Wistar rats without pregnancy and deliver were randomly
      divided into 6 groups: sham (sham-operation), ovariectomy (OVX), OVX +
      diethylstilbestrol, OVX + high dose RD (4 g x kg(-1) x d(-1)), OVX + middle dose
      RD (2 g x kg(-1) x d(-1)) and OVX + low dose RD (1 g x kg(-1) x d(-1)) (n = 5 in
      every group). After 12-week period of continuous treatment, the urinary samples
      and blood samples were collected for the determination of serum estrodiol (E2),
      calcium (Ca), phosphorus (P), bone glaprotein (BGP), alkaline phosphatase (ALP),
      urinary calcium/creatinine (Ca/Cr), phosphorus/ creatinine (P/Cr) and
      deoxypyridioline/creatinine (DPD/Cr). The uteri were removed and weighed. The
      bone mineral density (BMD) and the biomechanical parameters of the femur of the
      rats in every group were determined, respectively. RESULT: The coefficient of
      uteri in every dose group of OVX + RD was significantly higher than that in the
      OVX group (P < 0.01). The concentration of serum ALP, BGP and urinary DPD/Cr,
      Ca/Cr in the OVX group was significantly higher than that in the sham group (P <
      0.05), respectively, However, that in the every dose of OVX + RD was lower than
      that in the OVX group, respectively. There was no significan difference in the
      concentration of serum Ca, P and urinary P/Cr in every group, respectively. The
      bone mineral density (BMD) in the OVX group was (0.032 +/- 0.007) g x cm(-2) and
      was significantly lower than that in the sham group (P < 0.01). However, the
      value in the group of every dose OVX + RD was significantly higher than that in
      the OVX group (P < 0.05, P < 0.01), respectively. The maximum loading, deflection
      and the maximum strain of the femur in the OVX group were (125.78 +/- 15.48) N,
      (1.87 +/- 0.22) mm, (9.34 +/- 1.10) % and were significantly lower than those in
      the sham group (P < 0.05, P < 0.01), respectively. The maximum loading and
      maximum stress were increased in different extent in the every dose group of OVX
      + RD, respectively. CONCLUSION: The decoction of RD can inhibit bone absorption,
      decline bone turnover and improve the loss of bone in ovariectomized rats.

PMID- 18051906
TI  - [Protective effect of Jinhuang-1 on acute respiratory distress syndrome rats
      induced by oleic acid].
AB  - OBJECTIVE: To observe the protective effect of Jinhuang-1 (JH-1) on oleic acid
      induced acute respiratory distress syndrome (ARDS) in rats and provide a basis to
      clinical application. METHOD: Oleic acid was injected into the tail vein of rats
      and JH-1 were administered to rats. After four days, their blood were collected
      for the blood gas analysis. The superoxide dismutase (SOD), the malondialdehyde
      (MDA), nitic oxide (NO) content and the positive expression ratio of tumor
      necrosis factor-alpha (TNF-alpha) were determined. The pathological changes of
      microstructure of lung were observed. RESULT: The results demonstrated that JH-1
      could significantly increase PO2, reduce PCO2 of oleic acid-induced ARDS rats,
      increase the superoxide dismutase, decrease the malondialdehyde, nitic oxide
      content and the positive expression ratio of TNF-alpha, and improve the
      histological destruction on lung. CONCLUSION: JH-1 plays a protective role for
      ARDS rats induced by oleic acid. The mechanism is probably related to attenuating
      lipid peroxidation and decreasing NO content and the expression of TNF-alpha in
      lung.

PMID- 18051907
TI  - [Effects of ethyl acetate extract of Semen Hoveniae on liver microsomal
      cytochrome P450 isoenzyme in rat].
AB  - OBJECTIVE: To investigate the effects of the ethyl acetate extract of Semen
      Hoveniae (ESH) on liver microsomal cytochrome P450 isoenzyme in rats. METHOD: The
      rats were given orally the ESH in the doses of 0.14, 0.17, 0.2 g x kg (equivalent
      to the crude herb) for 10 days respectively. Rat liver microsomal cytochrome
      P450, NADPH-Cyt C reductase, erythromycin N-demethylase (ERD), Aniline
      hydroxylase (ANH), aminopyrine N-demethylase (ADM) activities were quantitated by
      UV chromatography. The levels of mRNA expression of CYP1A1, CYP2C11, CYP2E1 and
      CYP3A1 were detected by semi-quantitative reverse transcripatase-polymerase chain
      reaction (RT-PCR). RESULT: The cytochrome P450 content, NADPH-Cyt C reductase
      activities and erythromycin N-demethylase (ERD) activities were not affected.
      Aniline hydroxylase (ANH) activities in liver were decreased by up to35.1%;
      aminopyrine N-demethylase (ADM) activitiesin liver were increased by up to 42.4%.
      The mRNA expression of CYP1A1, CYP2C11 and CYP3A1 were found to be increased
      markedly. CONCLUSION: A specific effect of ESH on liver microsomal cytochrome
      P450 isoenzyme in rats was observed in this investigation. ESH had various
      effects on liver microsomal cytochrome P450 isoenzyme.

PMID- 18051908
TI  - [Effects of tetrandrine on Ang II-induced cardiomyocyte hypertrophy and p-ERK1/2
      expression].
AB  - OBJECTIVE: To observe effects of tetrandrine (Tet) on angiotensin II (Ang II)
      induced cardiomyocyte hypertrophy and the activity and expression of
      phosphorylated ERK1/2 (p-ERK1/2). METHOD: In the primary culture of neonatal rat
      cardiomyocytes, as indexes of cardiomyocyte hypertrophy, pulsation rate was
      measured under phase contrast microscope. Cell size was determined by cell
      morphology analytical system. The total protein was determined by coomassie
      brilliant blue and protein synthesis rate was measured by [3H]-Leucine
      incorporation. ERK activity was measured by immuno-precipitation. The expression
      of p-ERK1/2 was assessed using Western blot. RESULT: Tet can decrease Ang II
      induced elevations of the pulsation rate, cell size, total protein and protein
      synthesis rate; inhibit the activity and expression of p-ERK1/2. CONCLUSION: The
      anti-hypertrophic effect of Tet on Ang II-induced cardiomyocyte hypertrophy was
      associated with inhibition of ERK1/2 signaling pathway.

PMID- 18051909
TI  - [Effect of total flaveos of Gymostemma pentaphyllum on protein expression of
      Fas/FasL genes and TNF-alpha concentration in cultured neonatal rat
      cardiomyocytes with hypoxia-reoxygenation].
AB  - OBJECTIVE: To study the effect of total flaveos of Gymostemma pentaphyllum on the
      protein expression of apoptosis-associated Fas/FasL gene and tumor necrosis
      factor-alpha (TNF-alpha) concentration in cultured neonatal rat cardiomyocytes
      with hypoxia-reoxygenation (H/R). METHOD: A cultured primary neonatal rat
      cardiomyocytes model with H/R was erected, experiments were divided into six
      groups, (1)control group, (2)H/R group, (3)15 mg x L(-1) TFG plus H/R group,
      (4)45 mg x L(-1) TFG plus H/R group, (5) 105 mg x L(-1) TFG plus H/R group,
      (6)105 mg x L(-1) TFG group. TNF-aconcentration in cultured cardiomyocytes with
      H/R, was determined by ELISA method, the protein expression of Fas/FasL genes
      were estimated by immunohisto-chemistry. RESULT: After cardiomyocytes were made
      with H/R, Compared with control group, the positive expression index (PEI) of
      Fas/FasL proteins in cardiomyocytes increased significantly, Compared with H/R
      groups, the PEI of Fas/FasL proteins were lower significantly in groups with
      different dosages of TFG (P < 0.05). TFG inhibited the secretion of TNF-alpha
      from myocardial cells and increased the survival rate of myocardial cells.
      CONCLUSION: The protein expression of apoptosis-associated Fas/FasL genes
      increased during H/R. The TFG can protect myocardium against H/R injury by
      decreasing the production of TNF-alpha, downregulating the protein expression of
      Fas/FasL genes, and then inhibiting myocyte apoptosis.

PMID- 18051910
TI  - [Clinical study of super crush-run Tongxinluo capsule on treatment of stroke].
AB  - OBJECTIVE: To evaluate the clinical efficacy and security of super crush-run tong
      xinluo capsule (SCTXLC) for apoplexy due to energy-deficiency and blood-stasis.
      METHOD: The randomised controlled double blind non-inferiority trial versus
      paroxetine, parallel contrast, different Kinds of Techniques and dosage, the
      clinical trial design was adopted, 144 patients with stroke of convalescent stage
      were selected by 2 group, which course of diseases was in 2 weekens to 3 months,
      neurological deficit scores was 8 to 30, grade of acaties of daily living scores
      was 2 to 5. the treatment group (n = 72) received SCTXLC 0.26 g (a capsule), 4
      capsules at a time, three times a day, while that of the control group (n = 72)
      received common crush-run tong xinluo capsule (CCTXLC) 0.38 g (a capsule), 4
      capsules at a time, three times a day, the therapeutic course for both groups was
      28 d. RESULT: The synthesis total effective rates of the stroke in treatment
      group and control group were 91.3% and 87.3% respectively, showing no significant
      difference. The Lower Bound Upper Bound of Asymptotic 95% Confidence Interval of
      the total effective rates difference is -4.57%, over the beforehand Lower Bound
      of 15%, non-inferiority trial versus paroxetine was eligible. The adverse
      reactions occurred was 1 patient in the treatment group and 2 patients in control
      group in clinical trial. CONCLUSION: SCTXLC has definite effect for apoplexy due
      to energy-deficiency and blood-stasis, the efficacy in the treated group was
      equal to that in the control group, and favourable satety for usage.

PMID- 18051911
TI  - [Review on experimental research of Chinese herbal medicine intervenion for
      breast cancer].
AB  - A review was about the mechanism of Chinese herbal medicine and its compounds
      intervening breast cancer in recent years. Experimental results showed that
      Chinese herbal medicine and its compounds have the activity of anti-cancer,
      through inhibiting the growth and proliferation of breast cancer cells,
      restraining the metastasis, appearing the estrogen-like activity and improving
      multi-drug resistance, and so on.

PMID- 18051912
TI  - Do we deserve trial by media?

PMID- 18051913
TI  - NICE guideline supports normal birth.

PMID- 18051914
TI  - Biological nurturing (2). The physiology of lactation revisited.

PMID- 18051915
TI  - Researching colic: a crying matter. Part 1: Causes and risk factors.

PMID- 18051916
TI  - The knitted breast project.

PMID- 18051917
TI  - Preconceptual care: why we need Foresight. Part 1: From diet to drugs.

PMID- 18051918
TI  - Intrapartum care guidance: putting women first.

PMID- 18051919
TI  - Midwifery basics: diet matters (2). Maternal overweight in pregnancy.

PMID- 18051920
TI  - Nuchal cord at birth: to cut or not to cut?

PMID- 18051921
TI  - Is there a future for normal birth? 2001.

PMID- 18051922
TI  - So you want to be a midwife? Part 5: Preparing for the interview.

PMID- 18051923
TI  - Birth by numbers.

PMID- 18051924
TI  - No child need have unrecognized diabetes mellitus.

PMID- 18051925
TI  - Non-alcoholic fatty-liver disease in pediatric populations.
AB  - The increasing prevalence of obesity is not only observed in adults. Children are
      affected by obesity and related diseases, such as chronic liver disease, more
      frequently than in the past. Nonalcoholic fatty-liver disease is an important
      cause of chronic liver disease and in the near future will become important
      worldwide. Considering this phenomenon, it is important for gastroenterologists
      and hepatologists to be aware of the presence of nonalcoholic fatty-liver disease
      in pediatric populations and to treat it adequately. This practice will have
      important benefits for future generations. This review discusses the most
      important aspects in epidemiology, diagnostics and treatment of nonalcoholic
      fatty-liver disease in children.

PMID- 18051926
TI  - The rise of insulin and the fall of ghrelin.

PMID- 18051927
TI  - Ghrelin serum levels during oral glucose tolerance test in prepubertal obese
      children with insulin resistance.
AB  - BACKGROUND: An involvement of ghrelin in glucose metabolism has been suggested;
      nevertheless, the relationship between ghrelin and insulin resistance (IR)
      remains unclear. AIMS: 1. To investigate the effect of glucose loading on ghrelin
      in prepubertal obese children with IR. 2. To assess possible correlations between
      IR and changes in circulating ghrelin. PATIENTS AND METHODS: Twenty prepubertal
      obese, insulin-resistant and 18 age- and sex-matched lean children were studied.
      Fasting glucose, insulin and ghrelin levels were measured. In the obese group,
      measurements were repeated during an OGTT. RESULTS: Ghrelin levels were decreased
      at 60 min, but thereafter increased to baseline values. The fall in circulating
      ghrelin was negatively correlated with IR and the respective rise in insulin
      levels. CONCLUSIONS: In prepubertal, insulin-resistant obese children, ghrelin is
      significantly suppressed shortly after glucose intake. It is possible that the
      above effect is attenuated by IR and the resultant increase in insulin levels.

PMID- 18051928
TI  - Incidence of childhood type I and non-type 1 diabetes mellitus in a diverse
      population: the Chicago Childhood Diabetes Registry, 1994 to 2003.
AB  - BACKGROUND: Reports of increasing risk for type 1 (T1) and type 2 diabetes
      mellitus in youth are emerging, but information on socioeconomically diverse
      populations is limited. METHOD: The Chicago Childhood Diabetes Registry is a city
      wide study of patients 0-17 years old at onset. Incidence data came from medical
      records and interviews; census data provided denominators; analyses used Poisson
      regression. Non-type 1 (nT1) patients had a type 2-like clinical course or
      related indicators. RESULTS: There were 1,366 incident cases: 719 in non-Hispanic
      Black (NHB), 379 in Hispanic, 229 in non-Hispanic White (NHW), and 39 in children
      of other ethnicities. Average annual incidence was 16.0 (95% CI: 14.6,
      17.6)/10(5) for boys, 20.1 (18.3, 22.1)/10(5) for girls, and 18.1 (16.9,
      19.3)/10(5) overall. Risk was 21.6 (19.6, 23.8)/10(5) for NHB, 14.6 (13.0,
      16.4)/10(5) for Hispanic, and 18.1 (15.9, 20.6)/10(5) for NHW. Children aged 10
      14 years experienced the highest incidence, irrespective of ethnicity. T1 was
      predominant in all ethnic groups, except NHB, where the rates of T1 and nT1 were
      similar. Over ten years there was a marked increase in all childhood diabetes in
      Chicago, averaging 2.73% (95% CI: 0.49, 5.02) per annum, adjusted for age. This
      increase was confined to nT1, with an average annual percent change of +6.23%
      (2.28, 10.34), while T1 incidence remained stable. CONCLUSIONS: Incidence of
      childhood diabetes increased between 1994-2003, driven primarily by nT1,
      suggesting a role for behavioral and/or environmental determinants of insulin
      resistance. These estimates are likely to be conservative, if nT1 cases were more
      apt to be missed.

PMID- 18051929
TI  - Diabetes mellitus in Asian Indian children and adolescents.
AB  - AIM: To study the clinical and metabolic profile of type 1 and type 2 diabetes
      mellitus in children and adolescents in a South Asian population. RESEARCH DESIGN
      AND METHODS: Sixty children were recruited. They were divided into three groups:
      Group I--type 2 diabetes mellitus (DM2), Group II--type 1 diabetes mellitus
      (DM1), and Group III--healthy controls. The clinical history and biochemical
      parameters (HbA1c, serum insulin, C-peptide, triglycerides, total cholesterol and
      HDL-cholesterol) were recorded. Homeostasis model assessment for insulin
      resistance (HOMAIR) and quantitative insulin sensitivity check index (QUICKI)
      were calculated. RESULTS AND CONCLUSIONS: Children and adolescents with DM2 had a
      significant family history of DM and clinical features of insulin resistance,
      including increased body mass index, waist:hip ratio and acanthosis nigricans.
      They also had decreased insulin sensitivity together with dyslipidemia of
      metabolic syndrome, i.e. high triglyceride, high total cholesterol and low HDL
      cholesterol. The presence of these predictors of cardiovascular disorders is
      known to contribute to morbidity and mortality. Hence, DM2 needs to be recognized
      early in Asian Indian children.

PMID- 18051930
TI  - Decompensated hyperglycemic hyperosmolarity without significant ketoacidosis in
      the adolescent and young adult population.
AB  - AIM: To identify patients aged 10-30 years with probable hyperglycemic
      hyperosmolar syndrome (HHS), to describe demographic and clinical profiles, and
      to attempt to assess risk factors for poor outcomes. STUDY DESIGN: Retrospective
      cohort study (medical records review). SETTING: A 944-bed tertiary care teaching
      and research hospital and a 425-bed affiliated facility. PATIENTS: 10-30 year-old
      patients with a primary or secondary discharge diagnosis of HHS or diabetic
      ketoacidosis (DKA). Patients with a serum glucose >600 mg/dl in the absence of
      significant ketoacidosis (possible HHS) were profiled. Further stratification
      based on measured or calculated serum osmolarity >320 mOsm/kg (probable HHS) was
      undertaken. INTERVENTIONS: Patients received treatment for hyperglycemic crises,
      consisting primarily of fluids, electrolyte replacement and insulin. MEASUREMENTS
      AND MAIN RESULTS: Of the 629 admissions, 10 with a diagnosis of HHS and 33 with a
      diagnosis of DKA met the initial study criteria for HHS. 60% were African
      Americans and 89% were new-onset diabetics. From this group, 20 admissions had
      serum osmolarity > or =320 mOsm/kg. Fisher's exact test and Pearson coefficients
      were used to examine associations between risk factor and poor outcomes and
      correlations between admission data and length of hospital stay, respectively.
      Serious complications occurred in four patients (including two deaths, 10%
      mortality) and were limited to those with unreversed shock over the first 24
      hours of admission and who received <40 ml/kg of intravenous fluids over the
      first 6 hours of treatment. CONCLUSIONS: HHS was underdiagnosed in this
      population and occurred disproportionately in African Americans. Serious
      complications occurred exclusively in those with unreversed shock and inadequate
      fluid resuscitation.

PMID- 18051931
TI  - Relationship between endothelial dysfunction, carotid artery intima media
      thickness and circulating markers of vascular inflammation in obese hypertensive
      children and adolescents.
AB  - BACKGROUND: Adhesion molecules released by dysfunctional endothelium are
      considered as markers of vascular inflammation in early atherosclerosis. Non
      invasive ultrasound methods are now available to detect first preclinical signs
      of the disease. AIM: To investigate the relationship between selected adhesion
      molecules and ultrasound indicators of early atherosclerosis: endothelial
      function measured by flow-mediated dilatation (FMD) and intima media thickness
      (IMT). PATIENTS: The study group consisted of 85 children, mean age 14.6 years,
      of whom 22 were obese, 31 were hypertensive, and 32 obese and hypertensive. The
      control group included 26 healthy children. METHODS: Adhesin concentrations were
      determined by ELISA. FMD and IMT were evaluated by ultrasound. RESULTS: A
      positive correlation was found between sICAM-1 (soluble intercellular adhesion
      molecule 1) and IMT (r = 0.32, p = 0.013, 95% CI: 0.11 to 0.49) and a negative
      correlation between IMT and FMD (r = -0.26, p = 0.04, 95% CI: -0.43 to -0.04) in
      the whole study group. In the particular groups, we found significant
      correlations only in obese hypertensive children. sICAM-1 correlated positively
      with IMT (r = 0.52, p = 0.001, 95% CI: 0.2 to 0.72) and negatively with FMD (r = 
      0.31, p = 0.027, 95% CI: -0.6 to -0.2). sE-selectin correlated positively with
      IMT (r = 0.41, p = 0.012). In regression models, IMT correlated with sICAM-1
      (beta = 0.37, p = 0.03) and body mass index (beta = 0.55, p = 0.02), and FMD
      correlated negatively with sICAM-1 (beta = -0.47, p = 0.04). CONCLUSIONS: The
      association between inflammatory markers of the endothelium with impaired
      vasodilatation activity and the first atherosclerotic structural changes in the
      common carotid arteries were found in obese hypertensive children and
      adolescents. The coexistence of obesity and hypertension predisposes these young
      patients to closely related disturbances connected with early atherosclerosis.

PMID- 18051932
TI  - Ketoacidosis at onset of type 1 diabetes mellitus in children in Bosnia and
      Herzegovina: frequency and clinical presentation.

PMID- 18051933
TI  - Central precocious puberty associated with pituitary duplication and midline
      defects.
AB  - Central precocious puberty (CPP) is due to premature activation of the
      hypothalamic-pituitary-gonadal axis. It may be idiopathic or result from
      congenital or acquired CNS lesions. We describe a 7.4 year-old Brazilian girl
      with CPP who also presented hypertelorism, limitation of lateral neck rotation
      and synkinesis of the hands. Sellar and cervical column MRIs revealed pituitary
      duplication and rudimentary intervertebral disks. We present the clinical and
      imaging observations of this case, and a thorough literature review of this rare
      developmental abnormality.

PMID- 18051934
TI  - Mineralocorticoid deficiency in post-operative cerebral salt wasting.
AB  - Acute hyponatremia, following neurosurgery, results from inappropriate
      antidiuretic hormone secretion (SIADH) or cerebral salt wasting (CSW). CSW is due
      to abnormally high atrial or brain natriuretic peptides (ANP, BNP), which block
      all stimulators of zona glomerulosa steroidogenesis, resulting in
      mineralocorticoid deficiency. A 3 year-old girl presented CSW at day 4, after
      resection of craniopharyngioma and hypophysectomy. Hyponatremia, hyperkalemia and
      high natriuresis occurred on day 8, with low renin and aldosterone and elevated
      BNP 120.3 ng/ml (undetectable before surgery). Fludrocortisone 100 microg/day
      controlled natriuresis and restored electrolytes within 24 hours. A 5 year-old
      boy presented CSW at day 6 after partial resection of optic glioma.
      Fludocortisone 100 microg/day restored electrolytes within 8 hours. ANP was
      elevated, 60.6 ng/l, aldosterone and renin were low. Fludrocortisone
      supplementation should be considered in CSW, as excessive natriuresis is
      controlled, and electrolytes are easily restored, avoiding life-threatening
      complications of this complex disorder.

PMID- 18051935
TI  - Femoral hypoplasia in two newborns associated with maternal diabetes mellitus.
AB  - Femoral hypoplasia is a rare disorder, with an estimated incidence of 0.11
      0.2/10,000 live births. Although the majority of cases are sporadic, a few
      familial cases have been described. Poor diabetic control, exposure to drugs,
      viral infections, radiation, focal ischemia and trauma between the 4th and 8th
      week of gestation have been implicated as possible etiological factors. Femoral
      hypoplasia with other congenital anomalies was described in children of diabetic
      mothers. The isolated form is uncommon. We present here two newborns with femoral
      hypoplasia due to maternal diabetes mellitus. One of them has isolated and
      unilateral left femoral hypoplasia diagnosed after birth; the other has bilateral
      femoral hypoplasia and bowing diagnosed by ultrasound at 24 weeks' gestation.

PMID- 18051936
TI  - How should careproviders respond when the medical system leaves a patient short?

PMID- 18051937
TI  - Autonomy and the family as (in)appropriate surrogates for DNR decisions: a
      qualitative analysis of dying cancer patients' talk.

PMID- 18051938
TI  - What families say about surrogacy: a response to "autonomy and the family as
      (in)appropriate surrogates for DNR decisions".

PMID- 18051939
TI  - The armchair ethicist: it's all about location.

PMID- 18051940
TI  - Ethics consultation: continuing its analysis.

PMID- 18051941
TI  - Professional clinical ethicist: knowing why and limits.

PMID- 18051942
TI  - Memento ... life imitates art: the request for an ethics consultation.
AB  - This was a troublesome case, without complete consensus about the right thing to
      do. It seemed there were arguments on both sides: those who thought that the goal
      of comfort care without treatment was most consistent with his wishes, versus
      those who thought the additional testing and treatment might have produced a net
      benefit in spite of the burdens. Ultimately, the patient was placed in a facility
      with a do-not-resuscitate (DNR) order in effect and a plan for comfort care. He
      may live a few months or more. We all hope that whatever time he has is spent
      free of pain and symptoms, and that he is able to live a life of quality
      consistent with his wishes. The main story line is consistent with actual events;
      however, there have been changes in terms of gender, disease, and relationships
      that have been included to protect the anonymity of the patient.

PMID- 18051943
TI  - Memory identity and capacity.

PMID- 18051944
TI  - Decision-making capacity, memory and informed consent, and judgment at the
      boundaries of the self.

PMID- 18051945
TI  - The challenges of amnesia in assessing capacity, assigning a proxy, and deciding
      to forego life-prolonging medical treatment.

PMID- 18051946
TI  - Harvard Medical School Public Forum: insuring the uninsured: does Massachusetts
      have the right model? 17 May 2007.

PMID- 18051947
TI  - Multiplex reverse transcriptase-PCR assay for typing and subtyping of influenza A
      (H5 & H9) virus in Iran.
AB  - BACKGROUND: Avian influenza virus (AIV) infection is a major cause of bird or
      human mortality and morbidity, therefore the rapid identification of the virus is
      of important clinical and epidemiological implication. METHODS: A multiplex
      Reverse Transcriptase PCR (RT-PCR) was optimized for the detection of influenza A
      virus and the H5 and H9 subtypes. The influenza type A specific primers were
      directed to the region of the influenza A matrix gene that is conserved among
      most type A influenza viruses. The H5 and H9 primers were directed to H5 and H9
      hemagglutinin (HA) gene regions that are conserved among H5 and H9 subtypes. The
      selected primer sets were used in the RT-PCR for simultaneous detection of
      matrix, H5 and H9 responding specific sequences in a multiplex format. RESULTS:
      Three reaction conditions were optimized which include: i) RT-PCR typing using
      matrix gene primers for five subtypes of flu A (H1, H3, H5, H7 and H9), ii) RT
      PCR subtyping for H5 and H9 subtypes, and iii) multiplex subtyping of H5 and H9.
      In this study, the multiplex RT-PCR was applied to 147 cloacal and tracheal swabs
      of clinical poultry cases with similar influenza symptoms. CONCLUSIONS: These
      results suggest that multiplex RT-PCR assay can be a useful test for rapid
      detection and subtyping of AIV in clinical samples.

PMID- 18051948
TI  - Opioid receptors of the central amygdala and morphine-induced antinociception.
AB  - BACKGROUND: The amygdala is a forebrain region, which is known as a modulator of
      pain sensation. The amygdala, particularly the central nucleus, has high
      concentrations of enkephalins relative to dynorphins and has high concentrations
      of opioid receptors. We here studied the role of central nuclei of amygdala in
      morphine antinociception. METHODS: In this study, we used 130 male Wistar rats
      (200-250 g). Bilateral two guide cannula were inserted into central nuclei of
      amygdala. The drugs were administrated via intra central-amygdala and
      intraperitoneal. The antinociceptive effect was measured by formalin test.
      RESULTS: Bilateral microinjections of morphine (50 and 100 microg/rat) into the
      central nuclei of amygdala elicited powerful suppression of nociceptive behaviors
      in both phases of formalin test. The intraperitoneal administration of naloxone
      (1 and 2 mg/kg) decreased significantly the antinociception induced by the intra
      amygdaloid injection of morphine. Our data also showed that microinjection of
      naloxone (50 and 100 microg/rat) into the central nuclei of amygdala could reduce
      the analgesic effects of systemic morphine (7 mg/kg). On the other hand,
      bilateral neurotoxic lesions of the central nuclei of amygdala attenuated the
      antinociception induced by subcutaneous or intra-amygdaloid injection of
      morphine. CONCLUSION: These findings suggest that morphine analgesia in the
      formalin test depends on ascending connections to the forebrain, probably the
      amygdala.

PMID- 18051949
TI  - Isolation and identification of anionic surfactant degrading bacteria from
      activated sludge.
AB  - BACKGROUND: Linear alkylbenzene sulfonate (LABS) is an anionic surfactant widely
      used all over the world. They will eventually end-up and accumulate in household
      or industrial sewage. Due to their high foaming capabilities which can cause
      numerous problems in sewage treatment facilities as well as direct toxic effects
      on many different organisms in ecosystem; they are generally considered as
      serious pollutants. Many reports have indicated that common bacteria can readily
      degrade LABS. METHODS: In this survey, two different bacteria were isolated from
      Tehran municipal active sludge that showed the ability to degrade LABS rapidly
      and actively upon using it as their sole source of carbon. Biochemical tests as
      well as 16S rRNA gene sequencing performed. RESULTS: Results have indicated the
      two isolates to be Acinetobacter johnsoni and Pseudomonas beteli. After
      experiments to optimize the pH and temperature for growth of the two bacterial
      isolates, the extent of LABS, utilization was evaluated by HPLC method. The
      Pseudomonas beteli and Acinetobacter johnsoni isolates were able to degrade 96.4%
      and 97.2% of the original LABS levels after 10 days of growth, respectively.
      Mixed culture of the two isolates did not significantly increase LABS utilization
      (97.6%). CONCLUSION: Our study showed the ability of two isolated steains to
      rapidly biodegrade LABS under aerobic conditions.

PMID- 18051950
TI  - Effect of matrigel on function and morphology of human endometrial epithelial
      cell in vitro.
AB  - INTRODUCTION: The importance of extra cellular matrix (ECM) in development and
      function of different cells has been reported but little is known about its role
      in human endometrial epithelial cells. The aim of the present study was to
      examine effects of artificial ECM (Matrigel) and progesterone on the function and
      morphology of human endometrial epithelial cells in vitro. METHODS: Endometrial
      samples were removed, with informed patients consent and Ethics Committee
      approval, from 17 previously fertile women undergoing total abdominal
      hysterectomy. The tissue was dissociated and centrifuged to provide an epithelial
      rich suspension which was cultured either on plastic or seeded into Matrigel to
      produce polarized cells and then supplemented with or without progesterone (10(
      6) M). The amount of nucleic acid content of the cells in both in vitro model
      systems was examined by DNA, RNA extraction methods. The DNA and RNA content were
      later measured by spectrophotometry. RESULTS: The amount of total RNA in cells
      grown on Matrigel (23 +/- 1.5 pg/cell) was more than double that in cells grown
      on pllastic (9.1 +/- 1.4 pg/cell). Cells cultured on both in vitro model systems
      had RNA induced by steroid hormones, but the extent of induction was greater in
      cells grown on Matrigel (30 +/- 2 pg/cell) than those on plastic (12 +/- 1.9
      pg/cell). Cells cultured on Matrigel were differentiated and became polarized but
      cells grown on plastic proliferated to full confluency. Cells grown on Matrigel
      with progesterone supplementation were highly polarized, euchromatic and had
      greater mitochondria and accumulation of glycogen, when compared to
      unsupplemented cultures. CONCLUSION: These results suggest that ECM plays an
      important role in gene expression, polarization and differentiation of human
      endometrial epithelial cells in vitro. Endometrial cells grown on ECM responded
      to steroid hormone in a manner to that reported in endometrial cells in vivo.

PMID- 18051951
TI  - Characterization of beta-lactamases from urinary isolates of Escherichia coli in
      Tehran.
AB  - BACKGROUND: Knowledge of antimicrobial resistance patterns in E. coli, the
      predominant pathogen associated with urinary tract infections (UTI) is important
      as a guide in selecting empirical antimicrobial therapy. METHODS: To describe the
      antimicrobial susceptibility of E. coli associated with UTI in a major university
      hospital in Tehran (Iran), seventy-six clinical isolates of E. coli were studied
      for susceptibility to beta-lactam antibiotics by the disc diffusion method and
      Minimal Inhibitory Concentrations determination. RESULTS: All isolates were
      resistant to ampicillin, amoxicillin and oxacillin. Resistance to the other
      tested antibiotics was shown to be 93.4% to cefradine, 76.3% to carbenicillin,
      47.3% to cefazoline, 50% to cefalexin and 32.8% to cephalothin while 1.3%
      expressed resistance to cefoxitime, and 2.6% were resistant to ceftizoxime and
      ceftriaxone. Two isolates (2.4%) harbored extended spectrum ?-lactamases (ESBL)
      shown by the double disc diffusion method.  Substrate hydrolysis by ultra violet
      spectroscopy showed that 87.4% harbored penicillinases, 9% produced
      cephlosporinases and 3.6% degraded both substrates. Clavulanic acid inhibited
      enzyme activity in 82.9%, of which 78.95% was penicillinases (group IIa) and
      3.95% was cephalosporinases (group IIb) of the Bush classification system. The
      rest of the isolates (6.58 %) were placed in group IV ?-lactamases.  No group III
      ?-lactamase was found, as EDTA inhibited none of the enzymes. DNA amplification
      by polymerase chain reaction using specific primers for ampC, TEM and SHV type ?
      lactamases for all of the isolates showed that 47 organisms (60%) carried the TEM
      gene and 18 isolates (24%) harbored blaTEM and ampC genes. About 26% of the
      organisms harbored SHV type enzymes. type enzymes. CONCLUSION: These results
      indicate that E. coli can posses a variety of beta-lactamases that are
      responsible for beta-lactam resistance.

PMID- 18051952
TI  - Study of changes in some pathophysiological stress markers in different age
      groups of an animal model of acute and chronic heat stress.
AB  - BACKGROUND: This study demonstrates the changes in six different
      pathophysiological parameters such as body weight, body temperature, fecal pellet
      count, blood-brain barrier (BBB) permeability, plasma corticosterone level and
      emergence of hemorrhagic peptic ulcer spots due to exposure to high environmental
      heat in three different age groups of freely moving rats. METHODS: Each age group
      of rats was sub divided into three groups: (i) acute heat stress-subjected to a
      single exposure for four hours in the Biological Oxygen Demand incubator at 38
      degrees C; (ii) chronic heat stress-exposed for 21 days daily for one hour in the
      incubator at 38 degrees C, and (iii) handling control groups. The data were
      recorded for the analyses of the changes in different parameters just after the
      heat exposure from acute stressed rats and on 1st, 3rd, 6th, 9th, 12th, 15th,
      18th and 21st day on chronic stressed rats for body temperature, body weight,
      fecal pellets count. For the analysis of changes in three other parameters, BBB
      permeability, plasma corticosterone level and peptic ulcer spots following
      chronic exposure to high environmental heat, data were recorded on 22nd day for
      the analysis. RESULTS: Analysis of variance (ANOVA-1) of the observations
      demonstrates a significant increase in body temperature, fecal pellet count, BBB
      permeability (except in adult group), plasma corticosterone level and emergence
      of hemorrhagic peptic ulcer spots in all three different age group of rats due to
      exposure to acute heat stress. However, chronic heat was found responsible for
      the significant reduction in body weight in weaning and young rats, increase in
      body temperature, number of fecal pellets excreted (in early days of chronic
      stress) and number of peptic ulcer spots in all three age groups of rats. At the
      same time, BBB extravasations were not observed in rats except very mild in
      weaning group. CONCLUSION: The results of the present study indicate that the
      acute as well as chronic exposure to hot environment significantly alters the
      physiology of different organs of the body.

PMID- 18051953
TI  - Comparative effects of copper, iron, vanadium and titanium on low density
      lipoprotein oxidation in vitro.
AB  - INTRODUCTION: Oxidation of low density lipoprotein (LDL) has been strongly
      implicated in the phathogenesis of atherosclerosis. The use of oxidants in
      dietary food stuff may lead to the production of oxidized LDL and may increase
      both the development and the progression of atherosclerosis. The present work
      investigated the effects of some elements including: copper (Cu), iron (Fe),
      vanadium (V) and titanium (Ti) on in vitro LDL oxidation quantitatively. METHODS:
      The first LDL fraction was isolated from fresh plasma by single vertical
      discontinuous density gradient ultracentrifugation. The formation of conjugated
      dienes and thiobarbituric acid reactive substances and increase in
      electrophoretic mobility of LDL were monitored as markers of the oxidation of
      LDL. RESULTS: It was demonstrated that Cu, Fe, V and Ti exhibited strong oxidant
      activity in this respect (P<0.001). Oxidation of LDL in the presence of Cu was
      more and appeared to be in this order Cu>Fe>V>Ti. DISCUSSION: Cu, Fe, V and Ti
      are redox-active transition metals that may cause oxidative damage to lipids,
      proteins and DNA molecules. We suggest that these elements may also influence the
      oxidation of LDL in vivo, which could increase both the development and
      progression of atherosclerosis.

PMID- 18051954
TI  - The expression of signal regulatory protein-alpha in normal and osteoarthritic
      human articular cartilage and its involvement in chondrocyte mechano-transduction
      response.
AB  - BACKGROUND: Signal regulatory proteins (SIRP) belong to immunoglobulin super
      family (IgSF) and relate to integrin signaling cascades. It has been shown that
      SIRPalpha is expressed in a variety of cells including myeloid cells and neurons.
      In the present study the expression of this IgSF member in articular chondrocytes
      was investigated. METHODS: Using a panel of anti-SIRPalpha antibodies,
      immunohistochemistry, Western-blotting and electrophysiology methods, expression
      of SIRPalpha and its role in chondrocyte mechano-transduction were assessed.
      RESULTS: No identifiable positive signal was obtained by using
      immunohistochemistry methods on frozen and paraffin sections. SIRPalpha is
      expressed by both normal and osteoarthritis cultured chondrocytes. The
      electrophysiological response of chondrocytes in the presence of SE7C2 mAb was
      significantly inhibited whereas; SE5A5 did not show any modification in this
      response. CONCLUSIONS: It seems likely that SIRPalpha could be associated with
      other proteins such as integrins, CD47 and ion channels, which contribute to the
      electrophysiological response of human articular chondrocytes. In any case, this
      study has provided a specific functional role for SIRPalpha in chondrocyte
      mechano-transduction.

PMID- 18051955
TI  - Analysis of HLA-G gene expression in B-lymphocytes from chronic lymphocytic
      leukemia patients.
AB  - BACKGROUND: The human leukocyte antigen G (HLA-G) molecule exhibits limited
      tissue distribution, low polymorphism and alternative splicings that generate
      seven HLA-G isoforms. HLA-G exerts multiple immunoregulatory functions. Recent
      studies indicate an ectopic up-regulation in tumor cells that may favor their
      escape from anti-tumor immune responses. This study it is an effort to clarify
      the presence of HLA-G in B-cell chronic lymphocytic leukemia (B-CLL) patients.
      METHODS: HLA-G mRNA expression was studied in a pilot study in circulating B-CLL
      and also healthy controls by reverse transcription (RT)-PCR using a set of pan
      HLA-G primers. RESULTS: RT-PCR was performed on B-cells from 74 B-CLL patients
      and 12 healthy controls. The data showed HLA-G gene expression in 20% of the B
      CLL patients. No expression of HLA-G could be detected in the healthy control
      group. CONCLUSION: These data suggest that HLA-G is expressed at the gene level
      in B cells from B-CLL patients but not in B cells from healthy controls. Further
      study is required to clarify the role of HLA-G as a regulatory factor that could
      affect immune response in B-CLL patients.

PMID- 18051956
TI  - Preliminary report of NAD+-dependent amino acid dehydrogenase producing bacteria
      isolated from soil.
AB  - BACKGROUND: Amino acid dehydrogenases (L-amino acid: oxidoreductase deaminating;
      EC 1.4.1.X) are members of the wider superfamily of oxidoreductases that catalyze
      the reversible oxidative deamination of  an amino acid to its keto acid  and
      ammonia with the concomitant reduction of either NAD+, NADP+ or FAD. These
      enzymes have been received much  attention as biocatalysts for use in biosensors
      or diagnostic kits to screen amino acid metabolism disorders such as
      phenylketonuria (PKU), maple syrup urine disease (MSUD), homocystinuria (HCY) and
      hyperprolinemia. This study was aimed to isolation and screening of novel amino
      acid dehydrogenases from soil bacteriadehydrogenases from soil bacteria. METHODS:
      The enzyme producing bacteria were selected among L-methionine and L
      phenylalanine utilizers isolated from soil by thin layer chromatography, activity
      staining and confirmed by enzyme assay. Bacterial strains were identified by
      phenotypic and biochemical characteristics. The steady-state kinetic studies of
      enzymes were also performed. RESULTS: In total of 230 tested strains, four of
      them were recognized as amino acid dehydrogenase producers that belong to species
      of Pseudomonas, Citrobacter and Proteus. They exhibited the desired NAD+
      dependent dehydrogenase activities toward L-isoleucine, L-methionine, L-cysteine,
      L-serine and L-glutamine in oxidative deamination reaction. The specific activity
      of L-isoleucine dehydrogenase, L-methionine dehydrogenase and L-glutamine
      dehydrogenase for oxidative deamination of L-isoleucine, L-methionine and L
      glutamine were 1.59, 1.2 and 0.73 U/mg, respectively. The Kcat/Km (s(-1).mM(-1))
      values in these strains were as follows: L-isoleucine, 113.6, L-methionine, 62.05
      and L-glutamine, 95.83. CONCLUSION: This is the first report of occurrence a
      specific isoleucine dehydrogenase, glutamine dehydrogenase and methionine
      dehydrogenase in bacteria.

PMID- 18051957
TI  - ["Frog" in the mouth].

PMID- 18051959
TI  - [Even physicians underestimate the radiation load. The false picture of the CT].

PMID- 18051958
TI  - [Scars caused by navel piercing. Correction at the expense of insurance or the
      patient?].

PMID- 18051960
TI  - [Pre-travel prophylactic measures].
AB  - Before a patient embarks on a journey, his immunization status needs to be
      checked and, where applicable, booster vaccinations or specific vaccinations for
      the destination country given. In last-minute travelers, some vaccinations may
      still usefully be given - even up to the day of departure. Whether malaria
      prophylaxis is required for the planned country of destination should be checked
      against current recommendations.

PMID- 18051961
TI  - [Counseling the elderly traveler].
AB  - The medical counseling of senior citizens must take account of the physiological
      changes related to ageing as well as any previous illnesses. Points to be
      considered include booking (e.g. destination, handicapped ticket), pre-travel
      preparations (e.g. fit-to-travel, vaccinations, doctor's letters, first-aid kit,
      insurance) as also concrete on-tour information (e.g. monitoring of the amounts
      of fluid drunk, skin care, dietary recommendations).

PMID- 18051962
TI  - [The illnesses of a traveler returned from the tropics: how to deal with fever or
      diarrhea].
AB  - In patients returning from an endemic region who present with a feverish illness,
      malaria should always be the first disease you should suspect and investigate. In
      the case of uncomplicated traveler's diarrhea in the adult in contrast,
      unspecific symptomatic treatment suffices, and no specific diagnostic work-up is
      required. Only when certain alarm symptoms are present are further measures such
      as the search for pathogens or chemotherapy indicated.

PMID- 18051963
TI  - [Overcoming illness: good self-treatment for type 2 diabetes].

PMID- 18051964
TI  - [Radiculopathies and post-diskectomy syndrome. How neuropathic is backache?].

PMID- 18051965
TI  - [Chronic backache with neuropathic component. Individual basic therapy plus
      multimodal approach].

PMID- 18051966
TI  - [Internist patients are strongly thrombosis endangered. CERTIFY study has
      arrived].

PMID- 18051967
TI  - [LMWH and UFH in direct comparison. Consent: CERTIFY].

PMID- 18051968
TI  - [Colleagues' tips for avoidance of prescription errors. Thus we go forward
      against error devil].

PMID- 18051969
TI  - [Choice tariffs in the legal health insurance. Beginning of the end of the
      solidarity principle?].

PMID- 18051970
TI  - Building holistic bridges from life to death.

PMID- 18051971
TI  - Reflexology and intergrative imagery: promoting healing in patients, families &
      practitioners.

PMID- 18051972
TI  - Simple dying.

PMID- 18051973
TI  - My encounter with hospice.

PMID- 18051974
TI  - Palliative care assessment: screening for appropriateness.

PMID- 18051975
TI  - Using integrative therapies: from health to transition.

PMID- 18051976
TI  - Palliative care in a senior independent living community.

PMID- 18051977
TI  - I want to work in the gift shop where only the flowers die.

PMID- 18051978
TI  - Son Brian.

PMID- 18051979
TI  - Being an exemplary hospice nurse.

PMID- 18051980
TI  - The gift.

PMID- 18051981
TI  - Using healing touch for end of life care.

PMID- 18051982
TI  - Have you laughed today?

PMID- 18051983
TI  - Mary Natschke, 2007 Holistic Nurse of the Year. Interview by Lynne Nemeth.

PMID- 18051984
TI  - [Sound levels of the Piezosurgery. Risk of permanent damage to hearing].
AB  - In the past, research has regularly been carried out concerning the sound levels
      of various drilling devices and the impact these have on those who regularly use
      these devices. The present research is concerned with the possible permanent
      damage to hearing which can occur during the use of a newly developed instrument,
      the Piezosurgery. Measurements have been performed in a standardized set-up in
      which use is made of the lower jaws of pigs and a weight scale for measuring
      various degrees of pressure. The boundary values of the permissible exposure to
      noise were determined. The values of the Piezosurgery were compared with
      conventional drilling machines. It was concluded that using the Piezosurgery for
      less than 1.5 hours per day implies no risk of permanent damage to hearing. This
      means that the risk in the case of Piezosurgery is somewhat lower than that of
      conventional drilling devices.

PMID- 18051985
TI  - [Post-academic dental specialties 16. Post-academic specialization in
      maxillofacial prosthodontics].
AB  - Maxillofacial prosthodontics is a specialization in dental health practiced in
      centers for special dental care in The Netherlands by a limited number of
      dentists and technicians. The necessary skills, which are largely unique in the
      field of dentistry, were described in 2001 in a training program by the Dutch
      Association for Gnathology and Prosthodontics. Multidisciplinary diagnostics,
      treatment planning, and care delivery are taught in a modular system. A shortage
      of maxillofacial prosthodontists and maxillofacial technicians calls for a
      structural training of young colleagues.

PMID- 18051986
TI  - [Post-academic dental specialties 17. Implant-retained craniofacial prostheses].
AB  - The surgical and prosthetic aftercare of craniofacial prostheses supported by
      endosseous implants were registered in patients treated with implant-retained
      craniofacial prostheses in a university clinic during the last two decades.
      Aftercare was registered during the period from implant placement until the last
      follow-up visit. Implant survival rate was 95.2% in non-irradiated and 78.8% in
      irradiated bone. Discoloration of the silicon material, becoming loose of the
      acrylic clip carrier from the silicone, rupture of the silicone, and ill-fitting
      of the prosthesis were main reasons for fabrication of a new craniofacial
      prosthesis.

PMID- 18051987
TI  - [A fall onto the mouth].
AB  - A 34-year-old woman appeared at the office of a general dental practitioner after
      a bicycle accident. At first, the only injury seemed to be some small tooth
      enamel fractures. Several weeks later, she developed a swelling in the lower lip
      and was referred to an oral and maxillofacial surgeon. A radiograph of the lower
      lip revealed some of the tooth enamel fragments. This case-report illustrates the
      importance of a meticulous examination in case of a patient with a dental trauma.

PMID- 18051988
TI  - [Advanced glycation and lipoxidation end products--amplifiers of inflammation:
      the role of food].
AB  - Chronic diseases (CD) represent the main cause of mortality in developed
      countries. The increase in the prevalence of of CD is associated with changes in
      lifestyle habits, including those related to the consumption of processed
      foodstuffs. In these foods advanced glycation end products (AGE) and advanced
      lipoperoxydation products (ALE) are formed as a consequence of the reactivity of
      proteins, carbohydrates, lipid and other components. The aim of the present
      review is to offer a perspective of how AGE and ALE affect the physiology and
      development of CD. Continous intake of AGE and ALE contributes to the exccesive
      accumulation of these products into body tissues, which in turn negatively
      influence the innate immune system, inflammatory responses, and resistance to
      diseases. This is achieved by direct interaction of AGE and ALE with specific
      cell AGE receptors (RAGE) that have a key role as master switches regulating the
      development of CD. Long-life molecules, namely collagen and myelin, and low
      turnover tissues, e.g. connective, bone and neural tissues, are the main targets
      of AGE and ALE. In these tissues, AGE and ALE lead to the synthesis of insoluble
      compounds that severely alter cellular functionality. It has been reported
      associations of AGE and ALE with allergic and autoimmune diseases, Alzheimer
      disease and other degenerative disorders, catarats, atherosclerosis, cancer, and
      diabetes mellitus type 2, as well as a number of endocrine, gastrointestinal,
      skeleton-muscle, and urogenital alterations. Controlling all those pathologies
      would need further dietary recommendations aiming to limit the intake of
      processed foods rich in AGE and ALE, as well as to reduce the formation of those
      products by improving technological processes applicable to foods.

PMID- 18051989
TI  - [Nutrient intake in women with pagophagia and other forms of pica during the
      pregnancy].
AB  - OBJECTIVE: The aim of this investigation was to know and assess the
      characteristics of nutrient intake in pregnant women diagnosed with pica
      (consumption of non nutritive substances). MATERIALS AND METHODS: We studied a
      group of 71 women presenting pagophagia (compulsive consumption of ice) and other
      forms of pica, which was compared to a control group including the same number of
      women with similar socio-cultural and anthropometrical characteristics but
      without the eating disorder. Both groups were randomly selected among women
      assisted at the Hospital de la Matanza, province of Buenos Aires, Argentina.
      RESULTS: we did not observed statistically significant differences in energy,
      total proteins, iron, and calcium consumption. However, women with pica showed
      lower intakes (p < 0.03) of carbohydrates, animal proteins, hemic iron, and zinc.
      The median values for women with and without the disorder were, respectively:
      carbohydrates (g): 379/426; animal proteins (g): 35/39; hemic iron (mg): 1.5/1.9;
      zinc (mg): 7.1/8.1, calcium (mg): 625/612. In both groups, meat was the main
      source of iron and zinc, and its intake was lower in the group with pica. The
      daily average amounts consumed were 117 + 53 g for women with pica and 154 + 71 g
      (p < 0.03) for the control group. Only 22% of pregnant women with the disorder
      referred using iron supplements during their pregnancy. CONCLUSIONS: As compared
      with control women, pregnant women with pica disorder showed lower intake in
      traditionally marginal nutrients such as iron and zinc. These results show the
      need for early diagnosing this disorder during pregnancy in order to prevent or
      correct it and properly counseling pregnant women about food selection and
      supplementation regimens.

PMID- 18051990
TI  - Rice bran supplementation during nutritional recovery period of malnourished rats
      improves colon development.
AB  - OBJECTIVE: To investigate the colon's development in rats subjected to protein
      energy malnutrition followed by supplementation with rice bran. MATERIALS AND
      METHODS: Weaned Wistar male rats (21 days old), weight (40-50 g) were divided
      into two groups: diet with 17% protein (C; control group) or an aproteic diet (A;
      aproteic group), for 12 days. After this, 50% of the rats from each group were
      sacrificed. The remaining rats were further distributed in the three groups for a
      recovery (21 days): control (C) continued to receive the control diet whereas the
      aproteic group (A) received either a control diet (AC) or a control diet
      supplemented with 5% of rice bran (ARB). RESULTS: The A group showed alterations
      in the colon and cecum, excreted dry feces mass and fecal nitrogen, compared with
      C rats. In the proximal colon of A rats, the external muscularis and the width of
      the colon wall were higher whereas in the distal colon they were lower than C.
      After the recovery period, the relative cecum mass, colon mass and colon length
      of the recovered groups (AC and ARB) were higher than in the C group. Dry feces
      and fecal nitrogen excreted of the rats from recovered groups were lower than C
      group. Colon length of the AC group was lower than in the C group. Only the
      crypt's depth from ARB group was higher than in the C group. CONCLUSION: Control
      diet supplemented with 5% rice bran, reestablished the large intestine of
      aproteic rats. The recovery in the ARB group was even better than in the AC rats.

PMID- 18051991
TI  - [Dietary habits and their relationship with the knowledge on the concept of a
      balanced diet in a group of young women with overweight/obesity].
AB  - OBJECTIVE: To know the dietary habits of a population of women with
      overweight/obesity and their knowledge on the concept of proper feeding in order
      to design nutrition educational campaigns focused on this population. MATERIALS
      AND METHODS: A group of 67 women, aged 20 to 35 years with body mass index 24-35
      kg/m2 were asked about their frequency of food intake and what they thought to be
      correct to achieve a balanced diet. RESULTS: Studied women more frequently
      consumed oils (4.3 +/- 4.5 times/week) and sweets (2.5 +/- 3.6 times/week) and
      less frequently water (-19.1 +/- 22.7 times/week), vegetables (-4.3 +/- 5.7
      times/week), fruits (-3.7 +/- 6.2 times/week), legumes (-1.3 +/- 2.0 times/week)
      and fish (-2.2 +/- 3.7 times/week) than what they thought they should consume.
      When comparing what they declare to consume to what has been established as
      minimal recommended intake for the different groups of foods it is observed that
      the intake of grains and legumes, fruits and vegetables, and slightly less that
      of fish and eggs, should de increased. CONCLUSIONS: given the incorrect dietary
      habits observed in a population of women with overweight/obesity, it should be
      convenient to carry out nutrition educational campaigns. This education could
      help improve the diet of all the population and the occurrence of overweight and
      obesity could be prevented in many cases. Besides, in those cases in which the
      pathology is already present, this could prevent following regimens that are
      harmful for the health and for weight management.

PMID- 18051992
TI  - [Vitamin B complex and homocysteine in chronic renal failure].
AB  - Metabolic, biochemical, and hormonal changes occur in chronic renal failure
      usually associated with hyponutrition states. In predialysis patients, knowing
      the nutritional state about water-soluble vitamins such as thiamine, riboflavin,
      pyridoxine, cianocobalamine, and folic acid is becoming more and more important
      since some of the manifestations of chronic renal failure may be due to the
      deficiency of some of these water-soluble vitamins. The metabolic pathways in
      which most of these vitamins participate are interrelated and it is difficult to
      understand how the individual deficits of each vitamin affect renal pathology.
      This work aims at reviewing not only this issue but also the status of these
      water-soluble vitamins that different authors have found in groups of predialysis
      patients. On the other hand, the issue on the high prevalence of
      hyperhomocysteinemia in chronic renal failure as the main mortality risk factor
      due to cardiovascular pathologies as well as the implication of these vitamins in
      the metabolism of homocysteine, and consequently in plasma levels of this
      metabolite in predialysis patients is reviewed.

PMID- 18051993
TI  - Oral glutamine in addition to parenteral nutrition improves mortality and the
      healing of high-output intestinal fistulas.
AB  - OBJECTIVE: Anastomotic leakage is one of the most important causes of morbidity
      and mortality in gastrointestinal surgery. We investigated the effect of oral
      glutamine on the healing of high-output intestinal fistula. SETTING: A tertiary
      Universitary Hospital of the University of Mato Grosso, Cuiaba, Brazil. PATIENTS
      AND METHODS: 28 patients (25 males and 3 females; median age = 45 [18-71] years
      old) admitted with high output post-operative small bowel fistulas (median volume
      in 24 h: 850 [600-2,200] mL) during a 4 years period were retrospectively
      studied. INTERVENTIONS: In the first two years 19 (67.9%) patients received only
      TPN as the initial nutritional support. In the last two years however, due to a
      change in the protocol for the nutritional support in cases of intestinal fistula
      9 patients (32.1%) received oral glutamine (0.3 g/kg/day; 150 mL/day) in addition
      to TPN. Endpoints of the study were mortality, resolution of the fistula, and
      length of hospital stay (LOS). RESULTS: The overall mortality was 46.4% (13
      patients). Fistula closure was observed in all other 15 patients (53.6%) that
      survived. In the subset of survived patients LOS was similar in those who
      received or not received glutamine. The multivariate regression analysis showed
      that resolution of the fistula was 13 times greater in patients that received
      oral glutamine (OR = 13.2 (95% CI = 1.1-160.5); p = 0.04) and 15 times greater in
      non-malnourished patients (OR = 15.4 [95% CI = 1.1-215.5]; p = 0.04).
      CONCLUSIONS: We conclude that oral glutamine accelerated the healing and
      diminished the mortality in this series of patients with post-operative high
      output intestinal fistula receiving TPN.

PMID- 18051994
TI  - [Nutritional status in chronic renal failure patients assisted at the
      hemodialysis program of the "Hermanos Ameijeiras" Hospital].
AB  - INTRODUCTION: Heterogeneity of malnutrition rates associated with End-Stage Renal
      Disease (ESRD) under Haemodialysis (HD) points towards differing performances of
      the used indicators. OBJECTIVES: To identify those indicators that better
      describe the nutritional state of the patient with ESRD under HD. SETTING:
      Program of Haemodialysis, Service of Nephrology, "Hermanos Ameijeiras" Hospital
      (Havana City, Cuba). METHODS: Twenty-eight patients were recruited. Hospital
      admissions between december 2001-december 2002 were recorded. The condition of
      the patient (alive/deceased) after one year of observation was registered. The
      Subjective Global Assessment (SGA) form was administered to each patient. The
      nutritional profile included: height, weight, mid-arm circumference (MAC),
      triceps skinfold (TSF), albumin and total lymphocyte count (TLC). Nutritional
      status as described by means of albumin and MAC was correlated with SGA score,
      the ocurrence of hospital admissions and the final condition of the patient.
      RESULTS: Malnutrition rates were as follows (albumin < 35 g/L): 42.9%; (MAC < cut
      off value): 60.7%; [(MAC < cut-off value) and/or (albumin < 35)]: 71.4%; (SGA
      score = At Risk/Malnourished): 42.9%. SGA score was an independent predictor of
      the ocurrence of admissions [OR = 14.14; CI 95%: 1.5-137.3] and mortality [OR =
      21.0; CI 95%: 2.9-151.4]. Serum albumin was an independent predictor of the
      patient's mortality [OR = 21.0; CI 95%: 2.9-151.4]. The [(MAC < Cut-off value)
      and/or (albumin < 35)] rule failed to predict patient's morbimortality. Seventy
      seven point eight percent of patients with +60 years-old died during the year of
      observation [OR = 13.2; IC 95%: 1.9-89.5]. CONCLUSIONS: Increased mortality
      associated with diminished values of albumin and MAC justifies the fostering of
      nutritional intervention aimed to preserve lean tissues.

PMID- 18051995
TI  - [Nutritional aversions and preferences of 14-18 years old adolescents, schooled
      at the city of Santander].
AB  - OBJECTIVE: To describe the nutritional aversions and preferences of 14-18 years
      old adolescents schooled at Santander and analyze the changes taking place within
      the last decade. SUBJECTS: A cross-sectional study was carried out analyzing a
      sample of 1134 adolescents: 549 males (48.4%, 95% CI: 45.5%-5.3%) and 585 females
      (5.6%, 95% CI: 48.7%-54.5%), ages comprised between 14 and 18 years, and schooled
      at centers of secondary educational level from Santander, by means of a
      questionnaire. RESULTS: vegetables (54.7%) and legumes (18.7%) represent the main
      nutritional aversions of adolescents. On the other hand, grains (53.3%) and meats
      (14.6%) are the preferred foods. Lentils, lettuce, strawberry, water, and pasta
      generally were the best-valued foods within the groups of foods and drinks to
      which they belong. CONCLUSION: nutritional aversions and preferences of
      adolescents from Santander generally are very similar to those observed in other
      studies and we have not observed important changes within the last decade. The
      data obtained may be useful to observe future trends on nutritional preferences
      that, together with other parameters, may help characterized the nutritional
      behavior of our adolescents.

PMID- 18051996
TI  - [Prevalence of hyponutrition in the elderly at admission to the hospital].
AB  - BACKGROUND: The population older than 60 years in Mexico is growing changing the
      classic pyramidal demographic structure. This fact is increasing the risk of
      malnutrition in the elderly, specially under nutrition which is a common problem
      among elderly people living at home and during hospitalizations, condition that
      is closely related to the increasing of morbidity, mortality and costs.
      OBJECTIVE: Describe the prevalence of malnourished elderly who needs hospital
      admission. DESIGN: Cross-sectional observational study. SETTING: Third-level
      reference hospital. SUBJECTS: Ninety seven consecutive subjects older than 60
      years admitted to hospitalization. INTERVENTIONS: During the first three days of
      admission all subjects were evaluated to determine their nutritional status using
      Mini Nutritional Assessment and Subjective Global Assessment; albumin, total
      lymphocytes, level of income and school grade were also included. RESULTS: Just
      48% of patients have finished primary school and 66% had middle economic incomes.
      According to Mini Nutritional Assessment 69% of patients had risk associated to
      malnutrition (18% at high risk and 50% at moderate risk). The short form of the
      Mini Nutritional Assessment described 73% of patients at risk related to
      malnutrition in correlation with the complete Mini Nutritional Assessment. 46%
      and 20% of patients were classified at moderate malnutrition and severe
      malnutrition respectively using the Subjective Global Assessment. Kappa between
      Mini Nutritional Assessment and Subjective Global Assessment was of 42%. The
      Nutritional Risk Index mean value was of 85.9 +/- 11, with 80% of patients at
      risk associated with malnutrition when moderate and severe risk was included.
      Kappa between Nutritional Risk Index and Mini Nutritional Assessment was 11%. 70%
      of patients had serum albumin values under 3 g/dl. According to Chang's method
      52% had caloric undernutrition, 29% protein undernutrition and 18% mixed
      undernutrition. CONCLUSIONS: Malnutrition is a common problem in elderly
      population at hospital admissions according to different methods used. Mini
      Nutritional Assessment and Subjective Global Assessment are useful low cost and
      replicable nutritional evaluation tools in elderly population. Mini Nutritional
      Assessment could have a better value to predict morbidity and mortality in
      institutionalized and community elderly subjects.

PMID- 18051997
TI  - [Consensus on paediatric parenteral nutrition: a document approved by
      SENPE/SEGHNP/SEFH].
AB  - In current medical practice, standardization of procedures has become a desirable
      objective. The Spanish Society of Parenteral and Enteral Nutrition (SENPE) has
      undertaken a considerable effort to create clinical practice guidelines or
      documents of consensus and quality gold standards in artificial nutrition. As a
      result the SENPE group of standardization has put together a document called
      "Consensus of Paediatric Parenteral Nutrition" supported by the Spanish Society
      of Gastroenterology, Hepatology and Nutrition (SEGHNP) and by the Spanish Society
      of Hospital Pharmacies (SEFH). This is a reduced version of our work. The
      complete version is available at www.nutricionhospitalaria.com and www.senpe.com.
      This document covers many aspects such as paediatric patient indications,
      vascular access, macro and micro nutrients needs; also preparation in special
      situations, components, forms of prescription, possibilities for standardization
      of the elaboration and prescription, elaboration, administration, monitoring,
      complications and side effects. Much research has been done, incorporating
      current publications, books and clinical practice guidelines such as those
      published by the American Society for Parenteral and Enteral Nutrition (ASPEN)
      and by the European Society of Paediatric Gastroenterology, Hepatology and
      Nutrition (ESPGHAN) in collaboration with the European Society for Clinical
      Nutrition and Metabolism (ESPEN).

PMID- 18051998
TI  - [Patient with Crohn's disease and seizures due to hypomagnesemia].
AB  - We report a patient with Crohn's disease who suffered several generalized
      convulsions. He was studied with cerebral image techniques and neurophysiologic
      tests without getting the aetiology of the convulsions. A severe depletion in
      magnesium levels was suspected at the time of the initial evaluation by the
      Nutritional Team Group. Low serum magnesium levels were confirmed in the first
      blood test. Convulsions disappeared when magnesium was normalised by intravenous
      infusion. It is necessary for specialist physicians to be on the alert of severe
      complications of nutrients deficiency and that this kind of patients should be
      checked by the Nutrition Team.

PMID- 18051999
TI  - [Sucessful dietetic-therapy in primary intestinal lymphangiectasia and recurrent
      chylous ascites: a case report].
AB  - OBJECTIVES: Primary intestinal lymphangiectasia is a lymphatic system's disorder,
      where lymphatic drainage is blockaged. Clinically it produces malabsorption,
      protein-losing enteropathy, hypogammaglobulin in blood, and several degrees of
      malnutrition. Its treatment is not easy and includes dietetic-therapy and drugs.
      MATERIAL AND METHOD: A 35-year-old-woman case report is exposed. She has
      recurrent chylosa ascites, requiring several admissions and evacuatory
      paracentesis. After food-fat was replaced by medium-chain triacyl-glicerol
      enriched diet, a clinical, analytical and anthropometric improvement was
      demonstrated. CONCLUSIONS: The major way of treatment in intestinal
      lymphangiectasia in this case is the employement of specific-diet and adaptaded
      basic-food. It's difficult and high collaboration of the patient is required,
      being necessary medical revisions during the whole life, due to the not well
      known evolution of this long-standing disease.

PMID- 18052000
TI  - [Influence of nutrition and social environment on bone maturation in children].

PMID- 18052001
TI  - [Structure of populations and ecological nishes of ectoparasites in the parasite
      communities of small forest mammals].
AB  - The paper reports the results of eight-year investigations on the ectoparasites
      of rodents and insectivores carried out in southern taiga of the Ilmen-Volkhov
      lowland (Novgorod Region) and Kurgolovsky reserve (Leningrad Region). Twelve
      species of small mammals were captured including three dominate species--bank
      vole Clethrionomys glareolus (2722 specimens), common shrew Sorex araneus (1658
      specimens), and wood mouse Apodemus uralensis (367 specimens). Parasite community
      of the bank vole comprises 34 species of mites, ticks, and insects, the community
      of common shrew comprises 25 species, and the community of A. uralensis includes
      28 species. Taxonomic diversity of the ectoparasite communities was shown to be
      based on the diversity of types of parasitism and ecological nishes of the host
      body. Permanent ectoparasites are found to be represented by 2 species of lie and
      14 species of acariform mites. The group of temporary parasites includes 13
      species of fleas, 10 species of gamasid mites. 3 ixodid species and 1
      Trombiculidae. There is a common pool of temporary parasites of small mammals in
      the ecological system of taiga. Significance of different shrew and rodent
      species as hosts were found to be dependent on the population density in possible
      hosts and many other factors. Species diversity in the parasite communities of
      different small mammal species is dependent on the number of possible ecological
      nishes in the host body. Actual infill of these nishes by ectoparasites is
      usually lesser than potential one. Species composition of temporary parasites,
      their occurrence and abundance changes according to season. Interspecific
      competition in the temporary parasite species can decrease because of the
      seasonal disjunction of their population peaks. Diversification of the ecological
      niches of ectoparasites allow simultaneous feeding of more parasite individuals
      on one host, than in the case of parasitising of single species or several
      species with similar ecological nishes. The distribution of parasites on their
      hosts was also studied. The aggregative distribution has been found in ixodid
      larvae only, and the distribution of fleas was close to the Poisson distribution.
      Deviations from the aggregative distribution can be an effect of several
      independent factors, including limited ability of small mammals for providing
      numerous parasites with food. On the most part of hosts simultaneous parasitizing
      of no more than 1-3 individuals of each tick, mite, and flea species was
      registered. Excessive infestation by ectoparasites may probably be limited by
      effective reactions of self-purification in the mammal hosts.

PMID- 18052002
TI  - [Morpho-cytogenetic characteristic of the mosquito Anopheles artemievi (Diptera:
      Culicidae), a malaria vector from the complex maculipennis].
AB  - Detailed morphological analysis of all stages of the mosquito Anopheles artemievi
      Gordeev et al., 2005 is carried out. Characteristic traits that allow
      discriminating of An. artemievi and An. messeae Falleroni, 1926 in the area of
      joint occurrence of these two species are provided. Cytogenetic description of
      the polytene chromosomes from the nurse cells of ovaries is given. Differences of
      An. artemievi from previously studied species of the complex maculipennis by the
      structre of the polytene chromosomes from the nurse cells of ovaries are shown.

PMID- 18052003
TI  - [Species composition and ecological peculiarities of the mosquito genera Aedes
      and Anopheles (Diptera: Culicidae) in the Novgorod Region].
AB  - Five mosquito species form the genera Aedes and Anopheles are found in the
      Novgorod Region as a result of eight-year investigation (1997-2004). The species
      Ae. rossicus is for the first time recorded in the Novgorod Region.

PMID- 18052004
TI  - [Investigation of the sensory organs on antennae of the horseflies Hybomitra
      bimaculata and Tabanus bovinus (Diptera: Tabanidae) by scanning electron
      microscope].
AB  - Sensory organs on the antennae of the horseflies Hybomitra bimaculata Macq. and
      Tabanus bovinus Loew are represented by the same morphological types of sensilla.
      Never differences in the topographical distribution of the sensilla on antennae
      have been also found, which can be explained by the similarity of ecological and
      behavioural adaptations of these insects. First and second antennal segments are
      found to be supplied with tactile hairs and proprioceptors. Other antennal
      segments bear sensory organs of several morphological types. Short thin olfactory
      hairs are most numerous among them. They are present on all segments of the
      antennal flagellum and belong to two morphological types different by the hair
      length. In the upper parts of the antennal segments from third to seventh several
      sensilla trichoidea are present, which probably serve as tactile and taste
      receptors.

PMID- 18052005
TI  - [Component communities of parasites in the grayling Thymallus thymallus (L.)
      (Salmoniformes, Thymallidae) and the minnow Phoxinus phoxinus (L.)
      (Cypriniformes, Cyprinidae) from the Pechora River].
AB  - Component communities of parasites of Thymallus thymallus and Phoxinus phoxinus
      are described. The communities differ in the number of species and in the number
      of dominate species, which is one in P. phoxinus and usually two in T. thymallus.
      In the first case the dominate species is allogenic, while in the second case
      dominate species are autogenic. Values of the species diversity indexes are also
      different for these communities. The differences between parasite communities of
      T. thymallus and P. phoxinus underline positions of these hosts in
      hydrobiocenose. Species specialists take first place in the parasite communities
      both of the hosts, that is characteristic for the parasite communities of the
      fishes from the boreal submountain faunistic complex. Parasite communities in
      both of the hosts consist of three groups of species discriminated by the ratio
      of their biomasses, that suggests forming of the groups by a coordination of the
      species biomasses.

PMID- 18052006
TI  - [Helminthofauna of the common shrew Sorex araneus L. (Soricidae) from Samarskaya
      Luka].
AB  - Ecological analysis of the helminthofauna of common shrew Sorex araneus L. from
      Samarskaya Luka (Samara Region) has been carried out. Twenty-three helminth
      species are found including 3 species of trematodes, 8 cestodes, 10 nematodes,
      and 2 acanthocephales. Dependence of the structure of helminthofauna on the host
      age is revealed.

PMID- 18052007
TI  - [Relictolepis gen. n.--a new cestode genus (Cyclophyllidea: Hymenolepididae) from
      rodents of the Russian Far East and the description of R. feodorovi sp. n].
AB  - A new cestode genus and species Relictolepis feodorovi gen. et sp. n. having
      armed scolex is described ex Clethrionomis rufocanus Sundevall, 1846 (Rodentia,
      Microtinae) from the Russian Far East.

PMID- 18052008
TI  - Identifying patients at risk of chronic kidney disease.

PMID- 18052009
TI  - The CDC and USPSTF recommendations for HIV testing.

PMID- 18052010
TI  - It's time to normalize testing for HIV.

PMID- 18052011
TI  - Behavioral change counseling in the medical home.

PMID- 18052012
TI  - Temporomandibular joint disorders.
AB  - Temporomandibular joint disorders are common in adults; as many as one third of
      adults report having one or more symptoms, which include jaw or neck pain,
      headache, and clicking or grating within the joint. Most symptoms improve without
      treatment, but various noninvasive therapies may reduce pain for patients who
      have not experienced relief from self-care therapies. Physical therapy modalities
      (e.g., iontophoresis, phonophoresis), psychological therapies (e.g., cognitive
      behavior therapy), relaxation techniques, and complementary therapies (e.g.,
      acupuncture, hypnosis) are all used for the treatment of temporomandibular joint
      disorders; however, no therapies have been shown to be uniformly superior for the
      treatment of pain or oral dysfunction. Noninvasive therapies should be attempted
      before pursuing invasive, permanent, or semi-permanent treatments that have the
      potential to cause irreparable harm. Dental occlusion therapy (e.g., oral
      splinting) is a common treatment for temporomandibular joint disorders, but a
      recent systematic review found insufficient evidence for or against its use. Some
      patients with intractable temporomandibular joint disorders develop chronic pain
      syndrome and may benefit from treatment, including antidepressants or cognitive
      behavior therapy.

PMID- 18052013
TI  - Temporomandibular joint (TMJ) pain.

PMID- 18052014
TI  - Metastatic carcinoma of the long bones.
AB  - Breast, prostate, renal, thyroid, and lung carcinomas commonly metastasize to
      bone. Managing skeletal metastatic disease can be complex. Pain is the most
      common presenting symptom and requires thorough radiographic and laboratory
      evaluation. If plain-film radiography is not sufficient for diagnosis, a bone
      scan may detect occult lesions. Patients with lytic skeletal metastases may be at
      risk for impending fracture. Destructive lesions in the proximal femur and hip
      area are particularly worrisome. High-risk patients require immediate referral to
      an orthopedic surgeon. Patients who are not at risk for impending fracture can be
      treated with a combination of radiotherapy and adjuvant drug therapy.
      Bisphosphonates diminish pain and prolong the time to significant skeletal
      complications.

PMID- 18052015
TI  - Nonspecific low back pain and return to work.
AB  - As many as 90 percent of persons with occupational nonspecific low back pain are
      able to return to work in a relatively short period of time. As long as no "red
      flags" exist, the patient should be encouraged to remain as active as possible,
      minimize bed rest, use ice or heat compresses, take anti-inflammatory or
      analgesic medications if desired, participate in home exercises, and return to
      work as soon as possible. Medical and surgical intervention should be minimized
      when abnormalities on physical examination are lacking and the patient is having
      difficulty returning to work after four to six weeks. Personal and occupational
      psychosocial factors should be addressed thoroughly, and a multidisciplinary
      rehabilitation program should be strongly considered to prevent delayed recovery
      and chronic disability. Patient advocacy should include preventing unnecessary
      and ineffective medical and surgical interventions, prolonged work loss,
      joblessness, and chronic disability.

PMID- 18052016
TI  - Low back pain and your job: what you can do to get back to work.

PMID- 18052017
TI  - Acute pericarditis.
AB  - Although acute pericarditis is most often associated with viral infection, it may
      also be caused by many diseases, drugs, invasive cardiothoracic procedures, and
      chest trauma. Diagnosing acute pericarditis is often a process of exclusion. A
      history of abrupt-onset chest pain, the presence of a pericardial friction rub,
      and changes on electrocardiography suggest acute pericarditis, as do PR-segment
      depression and upwardly concave ST-segment elevation. Although highly specific
      for pericarditis, the pericardial friction rub is often absent or transient.
      Auscultation during end expiration with the patient sitting up and leaning
      forward increases the likelihood of observing this physical finding.
      Echocardiography is recommended for most patients to confirm the diagnosis and to
      exclude tamponade. Outpatient management of select patients with acute
      pericarditis is an option. Complications may include pericardial effusion with
      tamponade, recurrence, and chronic constrictive pericarditis. Use of colchicine
      as an adjunct to conventional nonsteroidal anti-inflammatory drug therapy for
      acute viral pericarditis may hasten symptom resolution and reduce recurrences.

PMID- 18052018
TI  - Mind-body therapies for headache.
AB  - Headache is one of the most common and enigmatic problems encountered by family
      physicians. Headache is not a singular entity, and different pathologic
      mechanisms are involved in distinct types of headache. Most types of headache
      involve dysfunction of peripheral or central nociceptive mechanisms. Mind-body
      therapies such as biofeedback, cognitive behavior therapy, hypnosis, meditation,
      and relaxation training can affect neural substrates and have been shown to be
      effective treatments for various types of headache. Meta-analyses of randomized
      controlled trials show that the use of mind-body therapies, alone or in
      combination, significantly reduces symptoms of migraine, tension, and mixed-type
      headaches. Side effects generally are minimal and transient.

PMID- 18052020
TI  - Predicting delirium in hospitalized older patients.

PMID- 18052019
TI  - Headaches and mind-body therapy: what you should know.

PMID- 18052021
TI  - Red, scaly lesion on the upper eyelid.

PMID- 18052022
TI  - Trends in active pharmaceutical ingredient salt selection based on analysis of
      the Orange Book database.
AB  - The Orange Book database published by the U.S. Drug and Food Administration (FDA)
      was analyzed for the frequency of occurrence of different counterions used for
      the formation of pharmaceutical salts. The data obtained from the present
      analysis of the Orange Book are compared to reviews of the Cambridge Structural
      Database (CSD) and of the Martindale "The Extra Pharmacopoeia". As well as
      showing overall distributions of counterion usage, results are broken down into 5
      year increments to identify trends in counterion selection. Chloride ions
      continue to be the most frequently utilized anionic counterions for the formation
      of salts as active pharmaceutical ingredients (APIs), while sodium ions are most
      widely utilized for the formation of salts starting from acidic molecules. A
      strong trend toward a wider variety of counterions over the past decade is
      observed. This trend can be explained by a stronger need to improve physical
      chemical properties of research and development compounds.

PMID- 18052023
TI  - 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2
      ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long
      acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2
      diabetes.
AB  - A new chemical class of potent DPP-4 inhibitors structurally derived from the
      xanthine scaffold for the treatment of type 2 diabetes has been discovered and
      evaluated. Systematic structural variations have led to 1 (BI 1356), a highly
      potent, selective, long-acting, and orally active DPP-4 inhibitor that shows
      considerable blood glucose lowering in different animal species. 1 is currently
      undergoing clinical phase IIb trials and holds the potential for once-daily
      treatment of type 2 diabetics.

PMID- 18052025
TI  - Novel amphiphilic probes for [18F]-radiolabeling preformed liposomes and
      determination of liposomal trafficking by positron emission tomography.
AB  - Positron-emission tomography (PET) is a noninvasive real-time functional imaging
      system and is expected to be useful for the development of new drug candidates in
      clinical trials. For its application with preformulated liposomes, we devised an
      optimized [18F]-compound and developed a direct liposome modification method that
      we termed the "solid-phase transition method". We were successful in using 1
      [18F]fluoro-3,6-dioxatetracosane ([18F]7a) for in vivo trafficking of liposomes.
      This method might be a useful tool in preclinical and clinical studies of lipidic
      particle-related drugs.

PMID- 18052024
TI  - Allosteric modulation of the dopamine receptor by conformationally constrained
      type VI beta-turn peptidomimetics of Pro-Leu-Gly-NH2.
AB  - A peptidomimetic of Pro-Leu-Pro-NH2, 7, possessing an indolizidinone type VI beta
      turn mimic was synthesized via improved high-yielding protocols for the
      preparation and Cbz protection of alpha-allylproline. Bicyclic peptidomimetic 7
      and spirobicylic peptidomimetic 8 enhanced the binding of [3H] N
      propylnorapomorphine to dopamine receptors indicating that a type VI beta-turn is
      a possible bioactive conformation of the homochiral Pro-Leu-Pro-NH2 and Pro-Pro
      Pro-NH 2 analogues of Pro-Leu-Gly-NH2 at the dopamine receptor allosteric
      regulatory site.

PMID- 18052026
TI  - Small, potent, and selective diaryl phosphonate inhibitors for urokinase-type
      plasminogen activator with in vivo antimetastatic properties.
AB  - A set of small nonpeptidic diaryl phosphonate inhibitors was prepared. Some of
      these inhibitors show potent and highly selective irreversible uPA inhibition.
      The biochemical and modeling data prove that the combination of a benzylguanidine
      moiety with a diaryl phosphonate ester results in optimized molecules for
      derivatizing the serine alcohol in the uPA active site. Selected compounds show
      significant antimetastatic effects in the BN-472 rat mammary carcinoma model. We
      report in this paper a preclinical proof of concept that selective, irreversible
      uPA inhibitors could be valuable in antimetastatic therapy.

PMID- 18052027
TI  - Biodegradable and pH-sensitive hydrogels for potential colon-specific drug
      delivery: characterization and in vitro release studies.
AB  - A novel pH-sensitive and biodegradable composite hydrogel, based on a
      methacrylated and succinic derivative of dextran, named Dex-MA-SA, and a
      methacrylated and succinic derivative of alpha,beta-poly( N-2-hydroxyethyl)- DL
      aspartamide (PHEA), named PHM-SA, was produced by photocross-linking. The goal
      was to obtain a colon-specific drug delivery system, exploiting both the pH
      sensitive behavior and the colon-specific degradability. The hydrogel prepared
      with a suitable ratio between the polysaccharide and the polyaminoacid was
      characterized regarding its swelling behavior in gastrointestinal simulated
      conditions, chemical and enzymatic degradability, interaction with mucin, and
      cell compatibility on CaCo-2 cells. Moreover, 2-methoxyestradiol was chosen as a
      model of anticancer drug and release studies, were performed in the absence or in
      the presence of dextranase and esterase. The obtained hydrogel, due to its pH
      sensitive swelling and enzymatic degradability, together with mucoadhesion and
      cell compatibility, could be potentially useful as system for the oral treatment
      of colonic cancer.

PMID- 18052028
TI  - Visual detection of labeled oligonucleotides using visible-light-polymerization
      based amplification.
AB  - DNA biochip technology holds potential for highly parallel, rapid, and sensitive
      genetic diagnostic screening of target pathogens and disease biomarkers. A
      primary limitation involves a simultaneous, sequence-specific identification of
      low copy number target polynucleotides using a clinically appropriate detection
      methodology that implements only inexpensive detection instrumentation. Here, a
      rapid (20 min), nonenzymatic method of signal amplification utilizing surface
      initiated photopolymerization is presented in glass microarray format. Visible
      light photoinitiators covalently coupled to streptavidin were used to bind biotin
      labeled capture sequences. Amplification was achieved through subsequent contact
      with a monomer solution and the appropriate light exposure to generate 20-240-nm
      thick hydrogel layers exclusively from spots containing the biotin-labeled DNA.
      An amplification factor of 10(6) to 10(7) was observed as well as a detectable
      response generated from as low as approximately 10(4) labeled oligonucleotides
      using minimal instrumentation, such as an optical microscope or CCD camera.

PMID- 18052029
TI  - Securinega alkaloids from the wood of Securinega suffruticosa var. amamiensis.
AB  - Three new Securinega alkaloids, secu'amamines B-D ( 1- 3), were isolated from the
      wood of the Japanese medicinal plant Securinega suffruticosa var. amamiensis,
      together with five known analogues ( 4, 6- 9). The structures 1- 3 were
      elucidated by spectroscopic methods including 2D NMR, and all eight compounds
      were evaluated for cytotoxicity against two cancer cell lines.

PMID- 18052030
TI  - An antiproliferative bis-prenylated quinone from the New Zealand brown alga
      Perithalia capillaris.
AB  - Bioactivity-directed isolation work on the endemic New Zealand brown alga
      Perithalia capillaris, seeking anti-inflammatory compounds, led to a new bis
      prenylated quinone ( 4). This compound inhibited superoxide production by human
      neutrophils in vitro (IC 50 2.1 microM), but was more potent at inhibiting
      proliferation of HL60 cells (IC 50 0.34 microM). Two related bis-prenylated
      phenols were also isolated, one known ( 2) and one new ( 5), with weaker
      biological activities. This report extends the examples of bis-prenylated phenols
      as chemotaxonomic markers for brown algae of the order Sporochnales.

PMID- 18052031
TI  - Evaluation of quantitative methods for the determination of polyphenols in algal
      extracts.
AB  - Marine brown algae such as Ascophyllum nodosum and Fucus vesiculosus accumulate
      polyphenols composed of phloroglucinol units. These compounds are of ecological
      importance and, due to their antioxidative activity, of pharmacological value as
      well. In this study four methods for the quantitative determination of
      phlorotannins are compared: spectrophotometric determinations using Folin
      Ciocalteu's phenol reagent or 2,4-dimethoxybenzaldehyde (DMBA), quantitative (1)H
      NMR spectroscopy (qHNMR), and gravimetrical measurements. On the basis of the
      relative standard deviation and the F-test, the determination using Folin
      Ciocalteu's phenol reagent and qHNMR proved to be the most reliable and precise
      methods.

PMID- 18052032
TI  - Real-time fluorescence monitoring of tryptic digestion in proteomics.
AB  - Ensuring that proteolytic digestions are complete before submitting samples for
      downstream proteomic analyses is important, as failure or partial digestion can
      waste valuable instrument time and make results difficult to interpret.
      Conversely, overdigestion can also be problematic, such as when removing affinity
      tags from recombinant proteins or using nonspecific proteases. The techniques of
      HPLC, circular dichroism, SDS-PAGE, and MS have each been used to assess protein
      digestion. These techniques are slow, may require expensive instrumentation, can
      be inaccurate, and/or are unsuitable for real-time monitoring. Epicocconone is a
      natural fluorophore that reacts reversibly with proteins to form a highly
      fluorescent adduct and has previously been used to quantify proteins in 1D and 2D
      gels and in solution. Here, we describe a new method for the real-time monitoring
      of protein digestion based on epicocconone. This unique in situ fluorescent assay
      can tracelessly follow proteolysis of samples, at low microgram levels, destined
      for proteomics analysis or purification.

PMID- 18052033
TI  - Species variation in the fecal metabolome gives insight into differential
      gastrointestinal function.
AB  - The metabolic composition of fecal extracts provides a window for elucidating the
      complex metabolic interplay between mammals and their intestinal ecosystems, and
      these metabolite profiles can yield information on a range of gut diseases. Here,
      the metabolites present in aqueous fecal extracts of humans, mice and rats were
      characterized using high-resolution (1)H NMR spectroscopy coupled with
      multivariate pattern recognition techniques. Additionally, the effects of sample
      storage and preparation methods were evaluated in order to assess the stability
      of fecal metabolite profiles, and to optimize information recovery from fecal
      samples. Finally, variations in metabolite profiles were investigated in healthy
      mice as a function of time. Interspecies variation was found to be greater than
      the variation due to either time or sample preparation. Although many fecal
      metabolites were common to the three species, such as short chain fatty acids and
      branched chain amino acids, each species generated a unique profile. Relatively
      higher levels of uracil, hypoxanthine, phenylacetic acid, glucose, glycine, and
      tyrosine amino acids were present in the rat, with beta-alanine being unique to
      the rat, and glycerol and malonate being unique to the human. Human fecal
      extracts showed a greater interindividual variation than the two rodent species,
      reflecting the natural genetic and environmental diversity in human populations.
      Fecal composition in healthy mice was found to change over time, which might be
      explained by altered gut microbial presence or activity. The systematic
      characterization of fecal composition across humans, mice, and rats, together
      with the evaluation of inherent variation, provides a benchmark for future
      studies seeking to determine fecal biomarkers of disease and/or response to
      dietary or therapeutic interventions.

PMID- 18052034
TI  - Effect of water deficit irrigation and inoculation with Botrytis cinerea on
      strawberry (Fragaria x ananassa) fruit quality.
AB  - Deficit irrigation (DI) detrimentally affected berry size but had a profound
      effect on fruit physiology and biochemistry. Strawberry cv. Elsanta fruit from DI
      treated plants had higher levels of abscisic acid (ABA). Dry matter content as a
      proportion of fresh weight was increased by a quarter in fruit from water
      stressed plants as compared to fruit harvested from plants held at or near field
      capacity. Concomitant to this, the concentration of some taste-related (viz.
      monosaccharides and sugar/acid ratios) and health-related compounds/parameters
      (viz. antioxidant capacity and total phenolics) were generally much greater in DI
      treated fruit. The effect of inoculation with Botrytis cinerea on fruit quality
      was also tested. Fruit derived from inoculated plants displayed symptoms of gray
      mold postharvest disease earlier than noninoculated fruit and had double the
      concentration of ABA. Inoculation had no significant effects on all other target
      analytes measured. There was no interaction between water treatment and
      inoculation. The possible mechanisms for increased synthesis of ABA and the
      different effects of pathogen-induced stress versus drought stress on fruit
      quality are discussed.

PMID- 18052035
TI  - Multivariate analysis for the evaluation of fiber, sugars, and organic acids in
      commercial presentations of table olives.
AB  - Table olives constitute an important part of the Mediterranean diet and the diet
      of many non-olive-producing countries. The aim of this work was to determine the
      fiber, sugar, and organic acid contents in Spanish commercial presentations of
      table olives and characterize them by means of a multivariate analysis. The
      selection of variables was carried out on the basis of a canonical analysis and
      their classification, according to processing styles and cultivars, through a
      linear discriminant analysis. Values of dietary fiber in table olives ranged from
      2 to 5 g/100 g edible portion (e.p.). Some stuffing materials (almond, hot red
      pepper, and hazelnut) or the addition of capers produced a significant increase
      in the total dietary fiber in green olives. Glucose, fructose, and mannitol were
      usually found in the ranges of 0-55, 0-70, and 0-107 mg/100 g e.p., respectively.
      Succinic acid was detected only in green and directly brined olives (0-40 mg/100
      g e.p.), while lactic and acetic acids were used within the ranges of 0-681 and 5
      492.8 mg/100 g e.p., respectively. A multivariate analysis showed that fiber,
      mannitol, and succinic, lactic, and acetic acids can be used to discriminate
      between processing styles (95.5% correct assignations) and cultivars (61.20%).
      Current data can also be used in the evaluation of the dietary value of table
      olives.

PMID- 18052036
TI  - Effect of milk protein concentrate on lipid oxidation and formation of fishy
      volatiles in herring mince (Clupea harengus) during frozen storage.
AB  - The effect of milk protein concentrate (MPC) at 0, 2, 4, and 6% on lipid
      oxidation and volatile formation in frozen stored herring mince (-18 degrees C)
      was evaluated by analyzing samples at 0, 2, and 4 months for fatty acid
      composition, volatiles, and thiobarbituric acid reactive substances (TBARS).
      Sensory evaluation was also conducted to assess the intensity of fishy odor, and
      the volatiles were analyzed using static headspace gas chromatography-mass
      spectrometry (SHGC-MS). The addition of 4 and 6% MPC to herring mince resulted in
      a 33% and 50% reduction of TBARS, respectively, at month 4 and lessened the
      intensity of fishy odor throughout storage. However, MPC did not protect fatty
      acids from enzymatic degradation unless it was added immediately after mincing.
      Volatile analysis using SHGC-MS showed that 4% MPC was able to reduce headspace
      volatiles associated with fishy odor. MPC is most effective for reducing 4
      heptenal, 3-methyl-1-butanol, 2-hexenal, and 1-penten-3-ol, which are known to be
      potent odorants associated with lipid oxidation.

PMID- 18052037
TI  - Coffee dietary fiber contents and structural characteristics as influenced by
      coffee type and technological and brewing procedures.
AB  - Coffee brews contain considerable amounts of soluble dietary fiber, mainly low
      substituted galactomannans and type II arabinogalactans. Factors possibly
      influencing the content and structures of dietary fiber in coffee brews, such as
      type of coffee, roasting and grinding degree, and brewing procedure, were
      studied. In addition, several commercial samples such as instant espresso,
      instant coffee, instant cappuccino, decaffeinated coffees, and coffee pads were
      analyzed. The dietary fiber contents of the coffee brews ranged from 0.14 to 0.65
      g/100 mL (enzymatic-gravimetric methodology), proving an influence of the factors
      investigated. For example, the drip brew of an arabica coffee contained
      significantly more soluble dietary fiber than the drip brew of a comparable
      robusta coffee, and depending on the brewing procedure, the soluble dietary fiber
      content of beverages obtained from the same coffee sample ranged from 0.26 to
      0.38 g/100 mL. Dietary fiber contents of coffee brews were enhanced only up to a
      certain degree of roast. Drip brews of decaffeinated arabica coffees (commercial
      samples) contained significantly less dietary fiber than any non-decaffeinated
      drip brew investigated in this study. The observed differences in the dietary
      fiber contents were accompanied by changes in the structural characteristics of
      fiber polysaccharides, such as galactomannan/arabinogalactan ratio, galactose
      substitution degree of mannans, or galactose/arabinose ratio of arabinogalactans
      as analyzed by methylation analysis.

PMID- 18052038
TI  - Assay of the set of all Sudan azodye (I, II, III, IV, and Para-Red) contaminating
      agents by liquid chromatography-tandem mass spectrometry and isotope dilution
      methodology.
AB  - A high-throughput mass spectrometric method is presented for the simultaneous
      detection of Sudan I, II, III, IV, and Para-Red azodyes in foodstuff. The method
      is based on the use of deuterium-labeled internal standards and atmospheric
      pressure chemical ionization (APCI) in a triple-quadrupole instrument. The gas
      phase breakdown pattern of each labeled and unlabeled analogue displays the
      naphthoic moiety as a common fragment. The search for the parents of this common
      species (parent ion scans) allows, by flow injection and in a single run, the
      evaluation of the presence of each polluting species spiked in typical
      foodstuffs. A detailed assay of each azodye was performed by LC-APCI and isotope
      dilution method, through the multiple reaction monitoring approach, using
      deuterium-labeled internal standards. Sudan dyes can be quantified above the
      threshold of 10 ppb except for Sudan Para-Red, for which the limit of
      quantification was 20 ppb, likely due to the different ionization efficiency.

PMID- 18052039
TI  - Predictive relationship between polyphenol and nonfat cocoa solids content of
      chocolate.
AB  - Chocolate is often labeled with percent cocoa solids content. It is assumed that
      higher cocoa solids contents are indicative of higher polyphenol concentrations,
      which have potential health benefits. However, cocoa solids include polyphenol
      free cocoa butter and polyphenol-rich nonfat cocoa solids (NFCS). In this study
      the strength of the relationship between NFCS content (estimated by theobromine
      as a proxy) and polyphenol content was tested in chocolate samples with labeled
      cocoa solids contents in the range of 20-100%, grouped as dark (n = 46), milk (n
      = 8), and those chocolates containing inclusions such as wafers or nuts (n = 15).
      The relationship was calculated with regard to both total polyphenol content and
      individual polyphenols. In dark chocolates, NFCS is linearly related to total
      polyphenols (r2 = 0.73). Total polyphenol content appears to be systematically
      slightly higher for milk chocolates than estimated by the dark chocolate model,
      whereas for chocolates containing other ingredients, the estimates fall close to
      or slightly below the model results. This shows that extra components such as
      milk, wafers, or nuts might influence the measurements of both theobromine and
      polyphenol contents. For each of the six main polyphenols (as well as their sum),
      the relationship with the estimated NFCS was much lower than for total
      polyphenols (r2 < 0.40), but these relationships were independent of the nature
      of the chocolate type, indicating that they might still have some predictive
      capabilities.

PMID- 18052040
TI  - Carboxyl-terminal disulfide bond of acid sphingomyelinase is critical for its
      secretion and enzymatic function.
AB  - The human acid sphingomyelinase (ASM, EC 3.1.4.12), a lysosomal and secretory
      protein coded by the sphingomyelin phosphodiesterase 1 (SMPD-1) gene, catalyzes
      the degradation of sphingomyelin (SM) to ceramide and phosphorylcholine. We
      examined the structural-functional properties of its carboxyl-terminus (amino
      acids 462-629), which harbors approximately 1/3 of all mutations discovered in
      the SMPD-1 gene. We created four naturally occurring mutants (DeltaR608, R496L,
      G577A, and Y537H) and five serial carboxyl-terminal deletion mutants (N620, N590,
      N570, N510, and N490). Transient transfection of the His/V5-tagged wild-type and
      mutant recombinant ASM in Chinese hamster ovary cells showed that all the mutants
      were normally expressed. Nonetheless, none of them, except the smallest deletion
      mutant N620 that preserved all post-translational modifications, were found
      capable of secretion to the medium. Furthermore, only the N620 conserved
      functional integrity (100% activity of the wild type); all other mutants
      completely lost the ability to catalyze SM hydrolysis. Importantly, cell surface
      biotinylation revealed that mutant DeltaR608 transfected CHO cells and
      fibroblasts from a compound heterozygous Niemann-Pick disease type B (NPD-B)
      patient (DeltaR608 and R441X) have defective translocation to the plasma
      membrane. Furthermore, we demonstrated that the DeltaR608 and N590 were trapped
      in the endoplasmic reticulum (ER) quality control checkpoint in contrast to the
      wild-type lysosomal localization. Interestingly, while the steady-state levels of
      ubiquitination were minimal for the wild-type ASM, a significant amount of Lys63
      linked polyubiquitinated DeltaR608 and N590 could be purified by S5a-affinity
      chromatography, indicating an important misfolding in the carboxyl-terminal
      mutants. Altogether, we provide evidence that the carboxyl-terminus of the ASM is
      crucial for its protein structure, which in turns dictates the enzymatic function
      and secretion.

PMID- 18052043
TI  - Structural analysis of immunotherapeutic peptides for autoimmune Myasthenia
      gravis.
AB  - Myasthenia gravis (MG) and its animal model, experimental MG (EAMG), are
      autoimmune disorders in which major pathogenic antibodies are directed against
      the main immunogenic region (MIR) of the nicotinic acetylcholine receptor
      (nAChR). In an earlier attempt to develop peptide mimotopes capable of preventing
      the anti-MIR-mediated pathogenicity, the peptide Pep.1 was initially identified
      from phage display, and subsequently, Cyclic extended Pep.1 (Cyc.ext.Pep.1),
      which incorporates eight additional residues into the Pep.1 sequence and has an
      affinity for the anti-MIR antibody mAb198 3 orders of magnitude greater than that
      of Pep.1, was developed. In an animal model, Pep.1 shows no ability to inhibit
      mAb198-induced EAMG, whereas Cyc.ext.Pep.1 successfully blocks anti-MIR antibody
      198 (mAb198)-induced EAMG. Our aim in this study was to identify the structural
      characteristics related to the different affinities for mAb198 of Pep.1 and
      Cyc.ext.Pep.1 using NMR spectroscopy and alanine scanning analysis. The NMR
      structural analysis revealed that Pep.1 is very flexible in solution, whereas
      Cyc.ext.Pep.1 is highly rigid within a region containing several turn structures.
      Interestingly, TRNOE experiments revealed that mAb198-bound Pep.1, particularly
      in the region between Asn7 and Glu11, shows significant structural similarity to
      the region between Asn10 and Glu14 of Cyc.ext.Pep.1, which is critical for
      interaction with mAb198. We therefore conclude the higher affinity of
      Cyc.ext.Pep.1 for mAb198 reflects the fact that incorporation of additional
      residues producing a single disulfide bond endows Pep.1 with a conformational
      rigidity that mimics the structure of mAb198-bound Pep.1. Furthermore, our
      results suggest that cyclic extended peptides could be utilized generally as
      useful tools to optimize the affinity of phage library-derived peptide antigens.

PMID- 18052042
TI  - Importance of the C-terminal domain of Harc for binding to Hsp70 and Hop as well
      as its response to heat shock.
AB  - Hsp90 is a molecular chaperone that acts in concert with Hsp70 to mediate the
      folding of many important regulatory proteins (e.g., protein kinases) into
      functional conformations. The chaperone activity of Hsp90 is primarily regulated
      by its cochaperones. For example, the Hsp90 cochaperone Cdc37 recruits Hsp90 to
      protein kinases as well as inhibiting its ATPase activity to promote the binding
      of Hsp90 to protein kinases. Harc is a structurally related Hsp90 cochaperone
      with a three-domain structure in which the middle domain binds Hsp90. In contrast
      to Cdc37 though, Harc also binds to Hsp70 and Hop (Hsp70/Hsp90 organizing
      protein). Here we demonstrate that deletion of the C-terminal domain of Harc
      abolished the binding of Hsp70 and Hop and reduced the affinity of Hsp90 binding
      to Harc. Significantly, the C-terminal domain of Harc bound Hsp70, but it did not
      bind Hop or Hsp90. Size exclusion chromatography of cell lysates revealed that
      Hop only formed a complex with Harc in the presence of Hsp90 and Hsp70,
      consistent with a model in which the interaction of Hop with Harc is mediated via
      the binding of Hop to Harc-bound Hsp90 and Hsp70. Notably, heat shock resulted in
      a marked decrease in the solubility of Harc, a response that was further
      augmented by the deletion of the C-terminal domain of Harc. This latter finding
      is especially interesting given that bioinformatics analysis indicated that cells
      may express splice variants of Harc that encode C-terminally truncated Harc
      isoforms. Together, these findings indicate that the C-terminal domain of Harc is
      a key determinant of its cochaperone functions.

PMID- 18052041
TI  - Structure of the DNA-binding domain of the response regulator PhoP from
      Mycobacterium tuberculosis.
AB  - The PhoP-PhoR two-component signaling system from Mycobacterium tuberculosis is
      essential for the virulence of the tubercle bacillus. The response regulator,
      PhoP, regulates expression of over 110 genes. In order to elucidate the
      regulatory mechanism of PhoP, we determined the crystal structure of its DNA
      binding domain (PhoPC). PhoPC exhibits a typical fold of the winged helix-turn
      helix subfamily of response regulators. The structure starts with a four-stranded
      antiparallel beta-sheet, followed by a three-helical bundle of alpha-helices, and
      then a C-terminal beta-hairpin, which together with a short beta-strand between
      the first and second helices forms a three-stranded antiparallel beta-sheet.
      Structural elements are packed through a hydrophobic core, with the first helix
      providing a scaffold for the rest of the domain to pack. The second and third
      helices and the long, flexible loop between them form the helix-turn-helix motif,
      with the third helix being the recognition helix. The C-terminal beta-hairpin
      turn forms the wing motif. The molecular surfaces around the recognition helix
      and the wing residues show strong positive electrostatic potential, consistent
      with their roles in DNA binding and nucleotide sequence recognition. The crystal
      packing of PhoPC gives a hexamer ring, with neighboring molecules interacting in
      a head-to-tail fashion. This packing interface suggests that PhoPC could bind DNA
      in a tandem association. However, this mode of DNA binding is likely to be
      nonspecific because the recognition helix is partially blocked and would be
      prevented from inserting into the major groove of DNA. Detailed structural
      analysis and implications with respect to DNA binding are discussed.

PMID- 18052044
TI  - Topological features of both electron density and electrostatic potential in the
      bis(thiosemicarbazide)zinc(II) dinitrate complex.
AB  - The experimental electron density of the bis(thiosemicarbazide)zinc(II) dinitrate
      complex, [Zn(CH5N3S)2](NO3)2,was studied. The Hansen-Coppens multipole model was
      used to extract the electron density from high-resolution X-ray diffraction data
      collected at 100 K. Careful strategies were designed for the electron density
      refinements regarding the charge transfer between the anionic and the cationic
      parts of the complex. Particular attention was also paid to the treatment of the
      electron density of the zinc atom interacting with two thiosemicarbazide ligands
      in a tetrahedral coordination. Nevertheless, the filled 3d valence shell of Zn
      was found unperturbed, and only the 4s shell was engaged in the metal-ligand
      interaction. Topological properties of both electron density and electrostatic
      potential, including kinetic and potential energy densities, and atomic charges
      were reported to quantify a metal-ligand complex with particular Zn-S and Zn-N
      bonds and hydrogen-bonding features. Chemical activities were screened through
      the molecular surface on which the three-dimensional electrostatic potential
      function was projected. The experimental results were compared to those obtained
      from gas-phase quantum calculations, and a good agreement was reached between
      these two approaches. Finally, among other electrostatic potential critical
      points, the values at the maxima corresponding to the nuclear sites were used as
      indices of the hydrogen-bonding capacity of the thiosemicarbazide ligand.

PMID- 18052045
TI  - Overtone-induced degradation of perfluorinated alcohols in the atmosphere.
AB  - Perfluorinated alcohols (PFOHs) are thermally unstable and degrade via loss of
      HF, ultimately forming perfluorocarboxylic acids. Experiments and calculations of
      the high activation barrier for the decomposition of CF3OH suggest that the
      reaction occurs exclusively heterogeneously, perhaps with the involvement of
      water. Here, we use density functional theory calculations to show that PFOHs may
      readily complex with water and are expected to be present as a few percent of the
      total PFOH concentration under ambient atmospheric conditions. The presence of
      water lowers the HF elimination barrier sufficiently that excitation to low-lying
      O-H vibrational overtone levels (vOH >or= 3) may cause reaction. Photolysis rate
      constants for CF3OH x H2O and CF3CF2OH x H2O were estimated to be 6.1 x 10(-8)
      and 5.6 x 10(-8) s(-1), respectively. PFOH-water complexes should undergo
      degradation much faster than the corresponding gas-phase unimolecular
      decomposition of PFOHs, which requires excitation into the vOH = 5 or 6
      vibrational level. Overtone-driven gas-phase reactions of PFOH-water complexes
      could be moderately competitive with heterogeneous reactions with water in dry
      locations. Overtone-induced degradation of PFOHs is likely a modest atmospheric
      source of PFCAs to the environment.

PMID- 18052046
TI  - Thermal behavior of 1,1-diamino-2,2-dinitroethylene.
AB  - The thermal behavior of 1,1-diamino-2,2-dinitroethlene (DADNE) was followed by
      differential scanning calorimetry (DSC) and thermogravimetry (TG). In addition,
      it was further investigated by the combination techniques of in situ thermolysis
      cell or fast thermolysis probe with rapid-scan Fourier transform infrared
      spectroscopy (thermolysis/RSFT-IR and fast thermolysis/RSFT-IR) and by mass
      spectroscopy (MS). The results showed that there was a phase transition (beta
      DADNE to gamma-DADNE) at the temperature of 119 degrees C, and that the gas
      products of DADNE consisted of CO2, CO, NO2, NO, N2O, HCN, and HNCO, of which
      CO2, NO, N2O, and HCN present themselves in both the first and second stages of
      DADNE decomposition process, whereas CO, NO2, and HNCO are only caused by the
      second stage, in air atmosphere. The C=C and C-NH2 bonds of DADNE molecules are
      broken in the first stage of the decomposition process in open air, and one of
      the C-NO2 and one of the C-NH2 bonds of the molecules are broken in the same
      stage under electrospray ionization condition.

PMID- 18052047
TI  - Self-interaction corrected density functional theory for the study of
      intramolecular electron transfer dynamics in radical carbocations.
AB  - We derived an orbital dependent Kohn-Sham based scheme for the correction of the
      self-interaction error in DFT, which is particularly suited for the study of open
      shell molecular systems. Our approach is based on a weighted form of the Perdew
      and Zunger (PZ) self-interaction correction scheme, in which an empirical
      coefficient is introduced in front of the SIC term to remove overcorrections. The
      method is used to investigate the first principle molecular dynamics of the
      intramolecular electron transfer (IET) in bis(methylene) adamanthyl radical
      cation and allows the analysis of the free energy surface that governs the IET
      process at room temperature (300 K). Indeed, the thermal activation of all
      molecular degrees of freedom provides important additional information about the
      mechanisms involved in the IET process. Our study confirms and extends previous
      results obtained with CASSCF and shows that there is no predominant degeneracy
      lifting mode even at room temperature. However, we also identified regions in the
      phase space for which there is a significant probability for a productive IET
      event. In addition, we performed thermodynamic integrations along selected
      reaction coordinates to determine an estimate of the activation free energy
      barrier for the IET process.

PMID- 18052048
TI  - Ozone reactions with alkaline-earth metal cations and dications in the gas phase:
      room-temperature kinetics and catalysis.
AB  - Room-temperature rate coefficients and product distributions are reported for the
      reactions of ozone with the cations and dications of the alkaline-earth metals
      Ca, Sr, and Ba. The measurements were performed with a selected-ion flow tube
      (SIFT) tandem mass spectrometer in conjunction with either an electrospray (ESI)
      or an inductively coupled plasma (ICP) ionization source. All the singly charged
      species react with ozone by O-atom transfer and form monoxide cations rapidly, k
      = 4.8, 6.7, and 8.7 x 10(-10) cm3 molecule(-1) s(-1) for the reactions of Ca+,
      Sr+, and Ba+, respectively. Further sequential O-atom transfer occurs to form
      dioxide and trioxide cations. The efficiencies for all O-atom transfer reactions
      are greater than 10%. The data also signify the catalytic conversion of ozone to
      oxygen with the alkaline-earth metal and metal oxide cations serving as
      catalysts. Ca2+ reacts rapidly with O3 by charge separation to form CaO+ and O2+
      with a rate coefficient of k = 1.5 x 10(-9) cm3 molecule(-1) s(-1). In contrast,
      the reactions of Sr2+ and Ba2+ are found to be slow and add O3, (k >/= 1.1 x 10
      11 cm3 molecule-1 s-1). The initial additions are followed by the rapid
      sequential addition of up to five O3 molecules with values of k between 1 and 5 x
      10(-10) cm3 molecule(-1) s(-1). Metal/ozone cluster ions as large as Sr2+(O3)5
      and Ba2+(O3)4 were observed for the first time.

PMID- 18052049
TI  - Rate coefficients for the OH + HC(O)C(O)H (glyoxal) reaction between 210 and 390
      K.
AB  - Rate coefficients, k1(T), over the temperature range of 210-390 K are reported
      for the gas-phase reaction OH + HC(O)C(O)H (glyoxal) --> products at pressures
      between 45 and 300 Torr (He, N2). Rate coefficients were determined under pseudo
      first-order conditions in OH using pulsed laser photolysis production of OH
      radicals coupled with OH detection by laser-induced fluorescence. The rate
      coefficients obtained were independent of pressure and bath gas. The room
      temperature rate coefficient, k1(296 K), was determined to be (9.15 +/- 0.8) x 10
      12 cm3 molecule-1 s-1. k1(T) shows a negative temperature dependence with a
      slight deviation from Arrhenius behavior that is reproduced over the temperature
      range included in this study by k1(T) = [(6.6 +/- 0.6) x 10-18]T2[exp([820 +/-
      30]/T)] cm3 molecule-1 s-1. For atmospheric modeling purposes, a fit to an
      Arrhenius expression over the temperature range included in this study that is
      most relevant to the atmosphere, 210-296 K, yields k1(T) = (2.8 +/- 0.7) x 10-12
      exp[(340 +/- 50)/T] cm3 molecule-1 s-1 and reproduces the rate coefficient data
      very well. The quoted uncertainties in k1(T) are at the 95% confidence level
      (2sigma) and include estimated systematic errors. Comparison of the present
      results with the single previous determination of k1(296 K) and a discussion of
      the reaction mechanism and non-Arrhenius temperature dependence are presented.

PMID- 18052050
TI  - Optical heterodyne detected accumulated acoustic grating responses in near
      supercritical fluids.
AB  - A novel third-order polarization effect due to an accumulated optical heterodyne
      detected (OHD) transient acoustic grating response in near critical fluids was
      observed and experimentally characterized. Femtosecond pump-probe responses in
      near critical CO2 and CHF3 illustrate this phenomenon. This large optically
      generated acoustic response due to electrostrictive coupling appears only when
      pump and probe pulses are temporally overlapped and is pi out-of-phase with the
      normal optical Kerr effect (OKE) birefringent signal. The local oscillator, the
      laser intensity, and the modeled experimental repetition rate dependence identify
      the accumulated heterodyne origin of these responses. The observed OHD
      accumulated acoustic birefringent signal is inversely dependent on sound velocity
      to the fifth power. A corresponding sound velocity dependent dichroic (in-phase)
      response was also observed for these electronically nonresonant samples. The
      accumulated effect described here may have applications for the design of
      efficient modulators and as a simple and sensitive experimental technique for the
      measurement of near critical fluid thermodynamic and acoustic parameters.

PMID- 18052051
TI  - Imaging the dynamics of reactions between Cl atoms and the cyclic ethers oxirane
      and oxetane.
AB  - Direct current slice velocity map ion images of the HCl(nu' = 0, J') products
      from the photoinitiated reactions of ground state Cl atoms with ethane, oxirane
      (c-C2H4O), and oxetane (c-C3H6O), at respective mean collision energies of 5.5,
      6.5, and 7.3 kcal mol-1(-1), were analyzed using a Legendre moment fitting
      procedure. The experimental method and the fitting technique were tested by
      comparing the derived center-of-mass (CM) frame angular scattering distribution
      for the HCl(v' = 0, J' = 1) products from the reaction of Cl + C2H6 with those
      determined by Suits and co-workers from a crossed molecular beam experiment. For
      the Cl + c-C2H4O reaction, a broad, forward, and backward peaking CM frame
      angular distribution of HCl(nu' = 0, J' = 2) products was determined, with an
      average fraction of the available energy released as product translational energy
      of f t, equal to 0.52 +/- 0.18. The HCl consumes only 1% of the available energy,
      and conservation arguments dictate that the radical coproduct is significantly
      internally excited, corresponding to an average fraction of the available energy
      of f int(c-C2H3O), equal to 0.47 +/- 0.18. For the reaction of oxetane with Cl
      atoms, abstraction of H atoms is possible from carbon atoms from positions either
      alpha or beta to the O atom. The contributions to the reaction from these two H
      atom abstraction channels were estimated to be 63 and 37%, consistent with an
      unbiased propensity for removal of alpha- and beta-H atoms that are present in
      2:1 abundance. The angular scatter of products in the CM frame is also broad and
      forward-backward peaking and is reminiscent of the products of the Cl + CH3OH and
      CH3OCH3 reactions. The derived mean fraction of the available energy channelled
      into product translation is f t = 0.54 +/- 0.12 for each of the two abstraction
      pathways. With only a small amount of energy in the rotation of the HCl(nu' = 0),
      the remainder is accounted for by excitation of the radical coproduct internal
      modes, with f int(c-C3H5O) = 0.42 +/- 0.12 for both alpha- and beta-H
      abstraction. The broad product scattering in the CM frame observed for both
      reactions of Cl atoms with the cyclic ethers is consistent with reactive
      collisions over a wide range of impact parameters, as might be expected for
      barrierless reactions with loose transition states.

PMID- 18052052
TI  - Hydrogen bonding in protonated water clusters: an atoms-in-molecules perspective.
AB  - This article highlights the results of a detailed study of hydrogen bonding in
      the first and the second solvation shells of Eigen (H3O+) and Zundel (H5O2+)
      cations solvated by water in a stepwise manner. It is evident from the results
      that an electron density analysis clearly distinguishes the first and the second
      solvation shell and helps in quantifying the strength of hydrogen bonding in
      these clusters.

PMID- 18052053
TI  - Study on nonlinear spectroscopy of tetraphenylporphyrin and dithiaporphyrin
      diacids.
AB  - The nonlinear absorption of two porphyrin diacids (H4TPP2+ and H2DSP2+), the
      diprotonated forms of free base tetraphenylporphyrin (H2TPP) and dithiaporphyrin
      (DSP), were studied in the wavelength range of 500-650 nm. The two porphyrin
      diacids exhibited perturbed static and dynamic characteristics and enhanced
      nonlinear absorption properties relative to their parent neutral complexes in
      solution. Furthermore, for the dithiaporphyrin diacid, the introduction of S
      atoms into the porphyrin core makes it a better candidate for optical limiting
      relative to the simple porphyrin. Their photophysical parameters such as ground
      and excited states absorption cross-sections, together with fluorescence lifetime
      and intersystem crossing time, were determined.

PMID- 18052054
TI  - Octacyanotungstate(V)-based magnetic complex consisting of dimeric Mn(2) and
      tetrameric Mn(2)W(2).
AB  - A novel zero-dimensional (0D) octacyanotungstate(V)-manganese(II) bimetallic
      assembly, {[MnII(bipy)2]2(ox)}.{[MnII(bipy)2W(CN)8]2}.4H2O (1) (bipy = 2,2'
      bipyridine, ox = C2O42-), was synthesized in methanol solution containing oxalic
      acid. X-ray analysis shows 1 is crystallized in monoclinic crystal system with
      C2/c space group and composed of two components of a dimeric Mn2 cation and a
      quadrate tetrameric Mn2W2 anion. The Mn2 and Mn2W2 moieties are connected by
      their respective pi-pi stacking to yield the alternative 2D layers, and the 2D
      layers are linked by hydrogen bonding to form a 3D network. The investigation of
      the magnetostructural correlation reveals that cyanide and oxalate bridges
      mediate weak intracluster antiferromagnetic coupling between Mn and W ions and
      between Mn ions, respectively. Further magnetic measurements and analysis show
      the spin glasses and intercluster ferromagnetic interaction exist in complex 1.

PMID- 18052055
TI  - Diorganoruthenium complexes incorporating noninnocent [C(6)H(2)(CH(2)ER(2))(2)
      3,5](2)(2-) (E = N, P) bis-pincer bridging ligands: synthesis,
      spectroelectrochemistry, and DFT studies.
AB  - The dinuclear complex [(tpy)RuII(PCP-PCP)RuII(tpy)]Cl2 (bridging PCP-PCP =
      3,3',5,5'-tetrakis(diphenylphosphinomethyl)biphenyl, [C6H2(CH2PPh2)2-3,5]22-) was
      prepared via a transcyclometalation reaction of the bis-pincer ligand [PC(H)P
      PC(H)P] and the Ru(II) precursor [Ru(NCN)(tpy)]Cl (NCN = [C6H3(CH2NMe2)2-2,6]-)
      followed by a reaction with 2,2':6',2' '-terpyridine (tpy). Electrochemical and
      spectroscopic properties of [(tpy)RuII(PCP-PCP)RuII(tpy)]Cl2 are compared with
      those of the closely related [(tpy)RuII(NCN-NCN)RuII(tpy)](PF6)2 (NCN-NCN =
      [C6H2(CH2NMe2)2-3,5]22-) obtained by two-electron reduction of [(tpy)RuIII(NCN
      NCN)RuIII(tpy)](PF6)4. The molecular structure of the latter complex has been
      determined by single-crystal X-ray structure determination. One-electron
      reduction of [(tpy)RuIII(NCN-NCN)RuIII(tpy)](PF6)4 and one-electron oxidation of
      [(tpy)RuII(PCP-PCP)RuII(tpy)]Cl2 yielded the mixed-valence species
      [(tpy)RuIII(NCN-NCN)RuII(tpy)]3+ and [(tpy)RuIII(PCP-PCP)RuII(tpy)]3+,
      respectively. The comproportionation equilibrium constants Kc (900 and 748 for
      [(tpy)RuIII(NCN-NCN)RuIII(tpy)]4+ and [(tpy)RuII(PCP-PCP)RuII(tpy)]2+,
      respectively) determined from cyclic voltammetric data reveal comparable
      stability of the [RuIII-RuII] state of both complexes. Spectroelectrochemical
      measurements and near-infrared (NIR) spectroscopy were employed to further
      characterize the different redox states with special focus on the mixed-valence
      species and their NIR bands. Analysis of these bands in the framework of Hush
      theory indicates that the mixed-valence complexes [(tpy)RuIII(PCP
      PCP)RuII(tpy)]3+ and [(tpy)RuIII(NCN-NCN)RuII(tpy)]3+ belong to strongly coupled
      borderline Class II/Class III and intrinsically coupled Class III systems,
      respectively. Preliminary DFT calculations suggest that extensive delocalization
      of the spin density over the metal centers and the bridging ligand exists. TD-DFT
      calculations then suggested a substantial MLCT character of the NIR electronic
      transitions. The results obtained in this study point to a decreased metal-metal
      electronic interaction accommodated by the double-cyclometalated bis-pincer
      bridge when strong sigma-donor NMe2 groups are replaced by weak sigma-donor, pi
      acceptor PPh2 groups.

PMID- 18052057
TI  - First-row transition metal-halide complexes supported by a monoanionic [N(2)P(2)]
      ligand.
AB  - Metal-halide complexes of a multidentate monoanionic ligand
      tBuN(H)SiMe2N(CH2CH2PiPr2)2, H[N2P2], with Ti, V, Cr, Mn, Fe, Co, and Ni have
      been isolated and characterized. X-ray crystallographic studies were performed on
      [N2P2]TiCl2 (3), [N2P2]CrCl2 (5), [N2P2]MnCl (6), [N2P2]FeCl (7), [N2P2]CoCl (8),
      and [N2P2]NiBr (9), and the results revealed that the [N2P2] ligand exhibits
      considerable flexibility in the manner in which it binds to first-row metals and
      that three distinct coordination modes are observed: kappa3-N2P (Ti), kappa3-NP2
      (Mn, Fe, Co), and kappa4-N2P2 (Cr, Ni). Electrochemical (CV) data and room
      temperature magnetic susceptibilities are also described.

PMID- 18052056
TI  - Synthesis and characterization of ruthenium bis(beta-diketonato) pyridine
      imidazole complexes for hydrogen atom transfer.
AB  - Ruthenium bis(beta-diketonato) complexes have been prepared at both the RuII and
      RuIII oxidation levels and with protonated and deprotonated pyridine-imidazole
      ligands. RuII(acac)2(py-imH) (1), [RuIII(acac)2(py-imH)]OTf (2), RuIII(acac)2(py
      im) (3), RuII(hfac)2(py-imH) (4), and [DBU-H][RuII(hfac)2(py-im)] (5) have been
      fully characterized, including X-ray crystal structures (acac = 2,4
      pentanedionato, hfac = 1,1,1,5,5,5-hexafluoro-2,4-pentanedionato, py-imH = 2-(2'
      pyridyl)imidazole, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene). For the acac
      imidazole complexes 1 and 2, cyclic voltammetry in MeCN shows the RuIII/II
      reduction potential (E1/2) to be -0.64 V versus Cp2Fe+/0. E1/2 for the
      deprotonated imidazolate complex 3 (-1.00 V) is 0.36 V more negative. The RuII
      bis-hfac analogues 4 and 5 show the same DeltaE1/2 = 0.36 V but are 0.93 V harder
      to oxidize than the acac derivatives (0.29 and -0.07 V). The difference in
      acidity between the acac and hfac derivatives is much smaller, with pKa values of
      22.1 and 19.3 in MeCN for 1 and 4, respectively. From the E1/2 and pKa values,
      the bond dissociation free energies (BDFEs) of the N-H bonds in 1 and 4 are
      calculated to be 62.0 and 79.6 kcal mol(-1) in MeCN - a remarkable difference of
      17.6 kcal mol(-1) for such structurally similar compounds. Consistent with these
      values, there is a facile net hydrogen atom transfer from 1 to TEMPO* (2,2,6,6
      tetramethylpiperidine-1-oxyl radical) to give 3 and TEMPO-H. The DeltaG degrees
      for this reaction is -4.5 kcal mol(-1). 4 is not oxidized by TEMPO* (DeltaG
      degrees = +13.1 kcal mol(-1)), but in the reverse direction TEMPO-H readily
      reduces in situ generated RuIII(hfac)2(py-im) (6). A RuII-imidazoline analogue of
      1, RuII(acac)2(py-imnH) (7), reacts with 3 equiv of TEMPO* to give the
      imidazolate 3 and TEMPO-H, with dehydrogenation of the imidazoline ring.

PMID- 18052058
TI  - Threshold CID investigation of isomeric Cu(I) azabox complexes.
AB  - An improved method for deconvoluting energy-resolved collision-induced
      dissociation cross sections yields ligand binding energies for organometallic
      complexes with substantially less prior information than before. Application to
      isomeric 2:1 complexes of azabox ligands with Cu(I) gives consistent results for
      the binding energies of the ligands to homo- and heterochiral complexes with
      pseudo-enantiomeric ligands for cases where previous deconvolution methods had
      failed to give satisfactory results.

PMID- 18052059
TI  - Combination of lacunary polyoxometalates and high-nuclear transition-metal
      clusters under hydrothermal conditions. 5. A novel tetrameric cluster of
      [{Fe(II)Fe(III)(12)(mu(3)-OH)(12)(mu(4)-PO(4))(4)}(B-alpha-PW(9)O(34))(4)](22)(
      ).
AB  - A novel tetrameric cluster, (enH2)3.5H15[{FeIIFeIII12(mu3-OH)12(mu4-PO4)4}(B
      alpha-PW9O34)4].83H2O (1; en = ethylenediamine), has been hydrothermally
      synthesized and characterized by IR, optical diffuse reflectance,
      thermogravimetric analysis, and single-crystal X-ray diffraction. The skeleton of
      1 is composed of four tri-FeIII-substituted [FeIII3(mu3-OH)3(B-alpha-PW9O34)]3-
      Keggin moieties fused together through a FeII2O2 unit and four mu4-PO4 bridges,
      resulting in a unique tetramer with C2 symmetry. Magnetic measurements indicate
      that 1 reveals the antiferromagnetic interactions between FeII and FeIII centers.

PMID- 18052060
TI  - Ambient-temperature metal-to-ligand charge-transfer phosphorescence facilitated
      by triarylboron: Bnpa and its metal complexes.
AB  - A Cu(I) complex, 1, and a Pt(II) complex, 2a, of a triarylboron ligand, Bnpa,
      with bright ambient-temperature phosphorescence have been obtained. The
      phosphorescence of these complexes is highly sensitive toward molecular oxygen
      and has a distinct response to fluoride ions. For 1, the fluoride ion causes
      phosphorescent quenching and Bnpa dissociation, and for 2a, it switches
      phosphorescent color from yellow to green. The Cu(I) complex has an exceptionally
      high emission quantum yield (0.88) in the solid state.

PMID- 18052061
TI  - Structural and initial biological analysis of synthetic arylomycin A2.
AB  - The growing threat of untreatable bacterial infections has refocused efforts to
      identify new antibiotics, especially those acting by novel mechanisms. While the
      inhibition of pathogen proteases has proven to be a successful strategy for drug
      development, such inhibitors are often limited by toxicity due to their
      promiscuous inhibition of homologous and mechanistically related human enzymes.
      Unlike many protease inhibitors, inhibitors of the essential type I bacterial
      signal peptidase (SPase) may be more specific and thus less toxic due to the
      enzyme's unique structure and catalytic mechanism. Recently, the arylomycins and
      related lipoglycopeptide natural products were isolated and shown to inhibit
      SPase. The core structure of the arylomycins and lipoglycopeptides consists of a
      biaryl-linked, N-methylated peptide macrocycle attached to a lipopeptide tail,
      and in the case of the lipoglycopeptides, a deoxymannose moiety. Herein, we
      report the first total synthesis of a member of this group of antibiotics,
      arylomycin A2. The synthesis relies on Suzuki-Miyaura-mediated biaryl coupling,
      which model studies suggested would be more efficient than a lactamization-based
      route. Biological studies demonstrate that these compounds are promising
      antibiotics, especially against Gram-positive pathogens, with activity against S.
      epidermidis that equals that of the currently prescribed antibiotics. Structural
      and biological studies suggest that both N-methylation and lipidation may
      contribute to antibiotic activity, whereas glycosylation appears to be generally
      less critical. Thus, these studies help identify the determinants of the
      biological activity of arylomycin A2 and should aid in the design of analogs to
      further explore and develop this novel class of antibiotic.

PMID- 18052062
TI  - A single residue switch converts abietadiene synthase into a pimaradiene specific
      cyclase.
AB  - Terpene synthases often catalyze complex cyclization reactions that typically
      represent the committed step in particular biosynthetic pathways, leading to
      great interest in their enzymatic mechanisms. We have recently demonstrated that
      substitution of a specific Ile with Thr was sufficient to "short circuit" the
      complex cyclization reaction normally catalyzed by ent-kaurene synthases to
      instead produce ent-pimaradiene. Here we report that the complex
      cyclization/rearrangement reaction catalyzed by abietadiene synthase can be
      similarly cut short to produce pimaradienes by an analogous Ser for Ala change,
      albeit with a slight shift in active site location to accommodate the difference
      in substrate stereochemistry. This result has mechanistic implications for
      enzymatic catalysis of abietadiene cyclization, and terpene synthases more
      broadly. Furthermore, these defined single residue switches may be useful in
      engineering product outcome in diterpene synthases more generally.

PMID- 18052063
TI  - Iron-catalyzed olefin epoxidation in the presence of acetic acid: insights into
      the nature of the metal-based oxidant.
AB  - The iron complexes [(BPMEN)Fe(OTf)2] (1) and [(TPA)Fe(OTf)2] (2) [BPMEN = N,N'
      bis-(2-pyridylmethyl)-N,N'-dimethyl-1,2-ethylenediamine; TPA = tris-(2
      pyridylmethyl)amine] catalyze the oxidation of olefins by H2O2 to yield epoxides
      and cis-diols. The addition of acetic acid inhibits olefin cis-dihydroxylation
      and enhances epoxidation for both 1 and 2. Reactions carried out at 0 degrees C
      with 0.5 mol % catalyst and a 1:1.5 olefin/H2O2 ratio in a 1:2 CH3CN/CH3COOH
      solvent mixture result in nearly quantitative conversions of cyclooctene to
      epoxide within 1 min. The nature of the active species formed in the presence of
      acetic acid has been probed at low temperature. For 2, in the absence of
      substrate, [(TPA)FeIII(OOH)(CH3COOH)]2+ and [(TPA)FeIVO(NCCH3)]2+ intermediates
      can be observed. However, neither is the active epoxidizing species. In fact,
      [(TPA)FeIVO(NCCH3)]2+ is shown to form in competition with substrate oxidation.
      Consequently, it is proposed that epoxidation is mediated by
      [(TPA)FeV(O)(OOCCH3)]2+, generated from O-O bond heterolysis of the
      [(TPA)FeIII(OOH)(CH3COOH)]2+ intermediate, which is promoted by the protonation
      of the terminal oxygen atom of the hydroperoxide by the coordinated carboxylic
      acid.

PMID- 18052064
TI  - A noncovalent switch for lysozyme.
AB  - A new concept for the external control of protein activity is presented and
      demonstrated on the example of an artificial Lysozyme switch. Radical
      copolymerization of selected methacrylamide-based comonomer units tailored for
      amino acid residues surrounding the active site furnishes polymeric protein hosts
      that are able to inhibit enzymatic activity in a highly efficient dose-dependent
      manner (IC50 approximately 1.0 equiv approximately 0.7 microM). All binding site
      types on the polymer work cooperatively, using electrostatic attraction,
      hydrophobic forces, and substrate mimicry. In a native gel electrophoresis, the
      well-defined 2:1 complex (polymer/protein) migrates to the anode. Even at 250 mM
      NaCl, a 10-fold polymer excess is able to shut down bacterial cell wall
      degradation completely. A kinetic investigation points to a competitive mechanism
      (Lineweaver-Burk plots). CD spectra of pure Lysozyme and its polymer complex are
      indistinguishable; together with a total lack of preincubation time for maximum
      inhibition, experimental evidence is thus produced for a preserved tertiary
      enzyme structure-no denaturation occurs. Addition of the superior complexing
      agent polyarginine to the enzyme-polymer complex mildly detaches the inhibitor
      from the protein surface and leads to 90% recovery of enzymatic activity. Thus,
      Lysozyme could be turned off, on, and off again by consecutive addition of the
      polymeric inhibitor, polyarginine, and polymer again.

PMID- 18052065
TI  - Direct detection of membrane channels from gels using water-in-oil droplet
      bilayers.
AB  - We form planar lipid bilayers between an aqueous droplet and a hydrogel support
      immersed in a lipid-oil solution. By scanning the bilayer over the surface of an
      SDS-PAGE gel, we are able to directly detect membrane proteins from gels using
      single-channel recording. Using this technique, we are able to examine low levels
      of endogenous protein from cell extracts without the need for over-expression. We
      also use droplet bilayers to detect small molecules from hydrogels. The bilayers
      show enhanced stability compared to conventional planar lipid bilayers, and both
      bilayer size and position can be controlled during an experiment. Hydrogel
      scanning with droplet bilayers provides a new method for the discovery and
      characterization of ion channels with the potential for high-throughput
      screening.

PMID- 18052066
TI  - Synthesis of [59]fullerenones through peroxide-mediated stepwise cleavage of
      fullerene skeleton bonds and X-ray structures of their water-encapsulated open
      cage complexes.
AB  - Fullerene skeleton modification has been investigated through selective cleavage
      of the fullerene carbon-carbon bonds under mild conditions. Several cage-opened
      fullerene derivatives including three [59]fullerenones with an 18-membered-ring
      orifice and one [59]fullerenone with a 19-membered-ring orifice have been
      prepared starting from the fullerene mixed peroxide 1, C60(OOtBu)6. The
      prepositioned tert-butyl peroxy groups in 1 serve as excellent oxygen sources for
      formation of hydroxyl and carbonyl groups. The cage-opening reactions were
      initiated by photoinduced homolysis of the tBu-O bond, followed by sequential
      ring expansion steps. A key step of the ring expansion reactions is the oxidation
      of adjacent fullerene hydroxyl and amino groups by diacetoxyliodobenzene (DIB).
      Aminolysis of a cage-opened fullerene derivative containing an anhydride moiety
      resulted in multiple bond cleavage in one step. A domino mechanism was proposed
      for this reaction. Decarboxylation led to elimination of one carbon atom from the
      C60 cage and formation of [59]fullerenones. The cage-opened [59]fullerenones were
      found to encapsulate water under mild conditions. All compounds were
      characterized by spectroscopic data. Single-crystal structures were also obtained
      for five skeleton-modified derivatives including two water-encapsulated
      fulleroids.

PMID- 18052067
TI  - A Molecular mechanism for the chemoselective hydrogenation of substituted
      nitroaromatics with nanoparticles of gold on TiO2 catalysts: a cooperative effect
      between gold and the support.
AB  - Nanoparticles of gold on TiO2 are highly chemoselective for the reduction of
      substituted nitroaromatics, such as nitrostyrene. By combining kinetics and in
      situ IR spectroscopy, it has been found that there is a preferential adsorption
      of the reactant on the catalyst through the nitro group. IR studies of
      nitrobenzene, styrene, and nitrostyrene adsorption, together with quantum
      chemical calculations, show that the nitro and the olefinic groups adsorb weakly
      on the Au(111) and Au(001) surfaces, and that although a stronger adsorption
      occurs on low-coordinated atoms in gold nanoparticles, this adsorption is not
      selective. On the other hand, an energetically and geometrically favored
      adsorption through the nitro group occurs on the TiO2 support and in the
      interface between the gold nanoparticle and the TiO2 support. Such preferential
      adsorption is not observed with nanoparticles of gold on silica which, contrary
      to the Au/TiO2 catalyst, is not chemoselective for the reduction of substituted
      nitroaromatic compounds. Therefore, the high chemoselectiviy of the Au/TiO2
      catalyst can be attributed to a cooperation between the gold nanoparticle and the
      support that preferentially activates the nitro group.

PMID- 18052068
TI  - A frequency domain existence proof of single-molecule surface-enhanced Raman
      spectroscopy.
AB  - The existence of single-molecule surface-enhanced Raman spectroscopy (SMSERS) is
      proven by employing a frequency-domain approach. This is demonstrated using two
      isotopologues of Rhodamine 6G that offer unique vibrational signatures. When an
      average of one molecule was adsorbed per silver nanoparticle, only one
      isotopologue was typically observed under dry N2 environment. Additionally, the
      distribution of vibrational frequencies hidden under the ensemble average is
      revealed by examining the single-molecule spectra. Correlation with transmission
      electron microscopy reveals that SMSERS active aggregates are composed of
      multiple randomly sized and shaped nanoparticles. At higher coverage and in a
      humid environment, adsorbate interchange was detected. Using 2D cross
      correlation, vibrational modes from different isotopologues were anti-correlated,
      indicating that the dynamic behavior was from multiple molecules competing for a
      single hot spot. This allows hot-spot diffusion to be directly observed without
      analyzing the peak intensity fluctuations.

PMID- 18052070
TI  - Ruthenium-catalyzed cycloaddition of aryl azides and alkynes.
AB  - The formation of 1,5-disubstituted 1,2,3-triazoles from aryl azides and alkynes
      was readily accomplished using [Cp*RuCl]4 catalyst in dimethylformamide. It was
      also demonstrated that the reaction provided higher yields, cleaner product, and
      shorter reaction times when carried out under microwave irradiation.

PMID- 18052069
TI  - Chemically adjusting plasma temperature, energy, and reactivity (CAPTEAR) method
      using NOx and combustion for selective synthesis of Sc3N@C80 metallic nitride
      fullerenes.
AB  - Goals are (1) to selectively synthesize metallic nitride fullerenes (MNFs) in
      lieu of empty-cage fullerenes (e.g., C60, C70) without compromising MNF yield and
      (2) to test our hypothesis that MNFs possess a different set of optimal formation
      parameters than empty-cage fullerenes. In this work, we introduce a novel
      approach for the selective synthesis of metallic nitride fullerenes. This new
      method is "Chemically Adjusting Plasma Temperature, Energy, and Reactivity"
      (CAPTEAR). The CAPTEAR approach with copper nitrate hydrate uses NOx vapor from
      NOx generating solid reagents, air, and combustion to "tune" the temperature,
      energy, and reactivity of the plasma environment. The extent of temperature,
      energy, and reactive environment is stoichiometrically varied until optimal
      conditions for selective MNF synthesis are achieved. Analysis of soot extracts
      indicate that percentages of C60 and Sc3N@C80 are inversely related, whereas the
      percentages of C70 and higher empty-cage C2n fullerenes are largely unaffected.
      Hence, there may be a "competitive link" in the formation and mechanism of C60
      and Sc3N@C80. Using this CAPTEAR method, purified MNFs (96% Sc3N@C80, 12 mg) have
      been obtained in soot extracts without a significant penalty in milligram yield
      when compared to control soot extracts (4% Sc3N@C80, 13 mg of Sc3N@C80). The
      CAPTEAR process with Cu(NO3)2.2.5H2O uses an exothermic nitrate moiety to
      suppress empty-cage fullerene formation, whereas Cu functions as a catalyst
      additive to offset the reactive plasma environment and boost the Sc3N@C80 MNF
      production.

PMID- 18052071
TI  - Indium-copper-mediated barbier-grignard-type alkylation reaction of imines in
      aqueous media.
AB  - An efficient system of In/CuI/InCl3 was developed for Barbier-Grignard-type
      alkylation reactions of simple imines, using a one-pot condensation of various
      aldehydes, amines (including aliphatic and chiral version), and alkyl iodides in
      water or aqueous media. The reactions proceeded efficiently at room temperature
      to give the desired products in moderate to good yields. Good
      diastereoselectivities were obtained when using L-valine methyl ester as
      substrate.

PMID- 18052072
TI  - C-H amination in synthesis: an approach to the assembly of the B/C/D ring system
      of aconitine.
AB  - A strategy for the preparation of aconitine is described that attempts to exploit
      chemoselective C-H amination and the electrophilic reactivity of oxathiazinane
      N,O-acetals for assembling the complex, polycyclic carbon framework of the
      natural product.

PMID- 18052073
TI  - Triazine dendrimers with orthogonally protected amines on the periphery. Masking
      amines with Dde and BOC groups provides an alternative to carrying protected
      alcohols and disulfides through an iterative synthesis.
AB  - An orthogonally protected dendrimer based on melamine displaying 24 Boc-protected
      amines (Boc is t-butoxycarbonyl) and 12 Dde-protected (Dde is N-2-(4,4-dimethyl
      2,6-dioxocyclohexylidene)ethyl) amines was synthesized using a convergent route
      in four linear steps in 43% overall yield to provide 5 g of product.
      Postsynthetic manipulation of this dendrimer produced a 57 kDa macromolecule
      bearing poly(ethylene glycol) groups and pyridyldisulfide groups linked via
      carbamate and amide bonds, respectively. These orthogonally protected amines
      provide more reactive handles for chemical modification when compared to other
      groups, notably hydroxyls, that have been explored. In addition, the Dde group
      proves to be more stable to the synthetic methods employed than do the disulfides
      used previously. Monochlorotriazine and dichlorotriazine intermediates are
      invaluable as a route for eliminating unwanted byproducts arising from over
      substitution of the triazine ring. Routes requiring three reactions on a simple,
      generation zero core versus six reactions on a generation one core are compared.

PMID- 18052074
TI  - Total synthesis of norbadione A.
AB  - A short, convergent synthesis of the mushroom pigment norbadione A is described.
      The construction of an appropriately substituted naphtholactone intermediate
      involved a regioselective Diels-Alder reaction between a
      bis(triisopropylsilyloxy)diene and 2,6-dichlorobenzo-1,4-quinone. A double Suzuki
      Miyaura cross-coupling between a diboronate and two identical enol triflates was
      another key feature of the synthesis.

PMID- 18052075
TI  - Retro-Diels-Alder reaction of 4H-1,2-benzoxazines to generate o-quinone methides:
      involvement of highly polarized transition states.
AB  - Here, we describe mechanistic studies of the retro-Diels-Alder reaction of 4H-1,2
      benzoxazines bearing various substituents on the benzene ring. 4H-1,2
      Benzoxazines are very simple, but quite new, heterocyclic compounds that afford
      substituted o-quinone methides (o-QMs) through retro-Diels-Alder reaction under
      mild thermal conditions. The resultant o-QMs undergo Diels-Alder reaction in situ
      with dienophiles to give phenol and chroman derivatives. The mechanism of the
      generation of o-QMs has been little studied. Our experimental and density
      functional theory (DFT) studies have yielded the following results. (1) The
      generation of o-QMs, i.e., the retro-hetero-Diels-Alder reaction of 4H-1,2
      benzoxazines, is rate determining, rather than the subsequent Diels-Alder
      reaction of the resultant o-QM with dienophiles. (2) The reaction rate is
      strongly influenced by the electronic features of substituents and the polarity
      of the solvent. The reaction proceeds faster in a polar solvent such as dimethyl
      sulfoxide, probably because of stabilization of the electronically polarized TS
      structure. (3) The reactions show characteristic positional effects of
      substitution on the benzene ring. While an electron-withdrawing group such as CF3
      at C5, C6, or C7 positions decelerates the reaction, the same substituent at C8
      accelerates the reaction, compared with the reaction of unsubstituted 4H-1,2
      benzoxazine. In particular, substitution at C5 significantly decelerates the
      reaction as compared with the unsubstituted case. This is due to the difference
      in the inductive effect of CF3 at the different positions. Similar positional
      effects occur with a halogen (Cl) and a nitro group. All these data support the
      involvement of polarized TS structures, in which the O-N bond cleavage precedes
      the C-C bond cleavage.

PMID- 18052076
TI  - Membrane interaction of chrysophsin-1, a histidine-rich antimicrobial peptide
      from red sea bream.
AB  - Chrysophsin-1 is an amphipathic alpha-helical antimicrobial peptide produced in
      the gill cells of red sea bream. The peptide has broad range activity against
      both Gram-positive and Gram-negative bacteria but is more hemolytic than other
      antimicrobial peptides such as magainin. Here we explore the membrane interaction
      of chrysophsin-1 and determine its toxicity, in vitro, for human lung fibroblasts
      to obtain a mechanism for its antimicrobial activity and to understand the role
      of the unusual C-terminal RRRH sequence. At intermediate peptide concentrations,
      solid-state NMR methods reveal that chrysophsin-1 is aligned parallel to the
      membrane surface and the lipid acyl chains in mixed model membranes are
      destabilized, thereby being in agreement with models where permeabilization is an
      effect of transient membrane disruption. The C-terminal RRRH sequence was shown
      to have a large effect on the insertion of the peptide into membranes with
      differing lipid compositions and was found to be crucial for pore formation and
      toxicity of the peptide to fibroblasts. The combination of biophysical data and
      cell-based assays suggests likely mechanisms involved in both the antibiotic and
      toxic activity of chrysophsins.

PMID- 18052077
TI  - GTP-binding-defective forms of tissue transglutaminase trigger cell death.
AB  - Tissue transglutaminase (TGase-2), which binds GTP and catalyzes the cross
      linking of proteins (transamidation), has been implicated both in the promotion
      of cell death and in the protection of cells against apoptotic insults. However,
      a novel transcript originally identified from the brains of Alzheimer's patients,
      encoding a truncated form of TGase-2 (called TGase-S), shows strong apoptotic
      activity. TGase-S exhibits no detectable GTP-binding capability, suggesting that
      its ability to induce cell death might be due to its inability to bind GTP. Thus,
      we have examined whether eliminating the GTP-binding capability of full-length
      human TGase-2 would prevent it from conferring protection against apoptotic
      challenges and instead convert it into a protein that causes cell death. A number
      of point mutants of human TGase-2 defective for binding GTP, as well as a mutant
      that shows impaired GTP-hydrolytic activity, were generated. Similar to what we
      had found for TGase-S, there was a time-dependent decrease in the expression of
      the GTP-binding-defective TGase-2 mutants in different cell lines, whereas the
      expression of wild-type TGase-2 and the GTP hydrolysis-defective mutant was
      sustained. Moreover, the GTP-binding-defective TGase-2 mutants induced cell
      death. The cell death responses triggered by these mutants were not due to their
      transdamidation activity, because double-mutants that were both GTP-binding- and
      transamidation-defective also stimulated cell death. Therefore, these results
      point to the inability to bind GTP as being sufficient for the apoptotic activity
      exhibited by the TGase-S protein. They also highlight a novel example of how the
      loss of GTP-binding activity can convert a protein that provides protection
      against apoptotic stimuli into a cell death-promoting factor.

PMID- 18052078
TI  - Steady state kinetics of spleen tyrosine kinase investigated by a real time
      fluorescence assay.
AB  - Spleen tyrosine kinase (Syk) is a cytoplasmic tyrosine kinase that plays an
      important signaling role in several types of immune cells. To improve our
      understanding of the enzymology and activation mechanism of Syk, we characterized
      the steady state kinetics of Syk substrate phosphorylation. A new real time
      fluorescence kinase assay was employed that utilizes a nonnatural amino acid in
      the peptide substrate which undergoes an enhancement in fluorescence following
      phosphorylation. Characterizing the steady state kinetics using a Syk kinase
      domain construct [Syk(360-635)] revealed that Syk employs a ternary complex
      kinetic mechanism involving little cooperativity between substrate binding sites
      and a Km(ATP) of 36 +/- 5 microM and a Km(peptide substrate) of 4.4 +/- 0.9
      microM. The order of substrate binding was determined to be either random or
      ordered with ATP binding first, as determined in substrate analogue inhibitor
      studies. Utilizing the real time capabilities of the fluorescence assay, we
      established that Syk demonstrates no lag phase in product formation. Furthermore,
      a Syk mutant lacking tyrosine in the activation loop (Syk Y525F,Y526F) exhibited
      activity identical to that of wild-type Syk. These two findings indicate that
      autophosphorylation of the activation loop of Syk does not regulate Syk(360-635)
      activity. We also compared the activity of Syk(360-635) to that of full-length
      Syk and revealed that Syk(360-635) is 10-fold more active, suggesting that
      residues outside the catalytic domain of Syk suppress kinase activity. The
      findings presented here provide the first kinetic description of the Syk enzyme
      mechanism.

PMID- 18052079
TI  - On the relationship between thermal stability and catalytic power of enzymes.
AB  - The possible relationship between the thermal stability and the catalytic power
      of enzymes is of great current interest. In particular, it has been suggested
      that thermophilic or hyperthermophilic (Tm) enzymes have lower catalytic power at
      a given temperature than the corresponding mesophilic (Ms) enzymes, because the
      thermophilic enzymes are less flexible (assuming that flexibility and catalysis
      are directly correlated). These suggestions presume that the reduced dynamics of
      the thermophilic enzymes is the reason for their reduced catalytic power. The
      present paper takes the specific case of dihydrofolate reductase (DHFR) and
      explores the validity of the above argument by simulation approaches. It is found
      that the Tm enzymes have restricted motions in the direction of the folding
      coordinate, but this is not relevant to the chemical process, since the motions
      along the reaction coordinate are perpendicular to the folding motions. Moreover,
      it is shown that the rate of the chemical reaction is determined by the
      activation barrier and the corresponding reorganization energy, rather than by
      dynamics or flexibility in the ground state. In fact, as far as flexibility is
      concerned, we conclude that the displacement along the reaction coordinate is
      larger in the Tm enzyme than in the Ms enzyme and that the general trend in
      enzyme catalysis is that the best catalyst involves less motion during the
      reaction than the less optimal catalyst. The relationship between thermal
      stability and catalysis appears to reflect the fact that to obtain small
      electrostatic reorganization energy it is necessary to invest some folding energy
      in the overall preorganization process. Thus, the optimized catalysts are less
      stable. This trend is clearly observed in the DHFR case.

PMID- 18052080
TI  - Inhibitors bound to Ca(2+)-free sarcoplasmic reticulum Ca(2+)-ATPase lock its
      transmembrane region but not necessarily its cytosolic region, revealing the
      flexibility of the loops connecting transmembrane and cytosolic domains.
AB  - Ca2+-free crystals of sarcoplasmic reticulum Ca2+-ATPase have, up until now, been
      obtained in the presence of inhibitors such as thapsigargin (TG), bound to the
      transmembrane region of this protein. Here, we examined the consequences of such
      binding for the protein. We found that, after TG binding, an active site ligand
      such as beryllium fluoride can still bind to the ATPase and change the
      conformation or dynamics of the cytosolic domains (as revealed by the protection
      afforded against proteolysis), but it becomes unable to induce any change in the
      transmembrane domain (as revealed by the intrinsic fluorescence of the membranous
      tryptophan residues). TG also obliterates the Trp fluorescence changes normally
      induced by binding of MgATP or metal-free ATP, as well as those induced by
      binding of Mg2+ alone. In the nucleotide binding domain, the environment of
      Lys515 (as revealed by fluorescein isothiocyanate fluorescence after specific
      labeling of this residue) is significantly different in the ATPase complex with
      aluminum fluoride and in the ATPase complex with beryllium fluoride, and in the
      latter case it is modified by TG. All these facts document the flexibility of the
      loops connecting the transmembrane and cytosolic domains in the ATPase. In the
      absence of active site ligands, TG protects the ATPase from cleavage by
      proteinase K at Thr242-Glu243, suggesting TG-induced reduction in the mobility of
      these loops. 2,5-Di-tert-butyl-1,4-dihydroxybenzene or cyclopiazonic acid,
      inhibitors which also bind in or near the transmembrane region, also produce
      similar overall effects on Ca2+-free ATPase.

PMID- 18052081
TI  - Magnetic-sensitive silica nanospheres for controlled drug release.
AB  - Recently, magnetic silica-based nanospheres have received great attention and
      displayed magnificent potential for bioimaging and therapeutic purposes. This
      study provided a way to accelerate drug release from magnetic-sensitive silica
      nanospheres by controlled bursting to a therapeutically effective concentration
      by a high-frequency magnetic field (HFMF). The magnetic-sensitive silica
      nanospheres were synthesized by an in situ process, with particle sizes about 50
      nm and able to release specific amounts of drug in a burst manner via short
      exposure to a HFMF. The HFMF accelerates the rotation of magnetic nanoparticles
      deposited in the silica matrix with generated heat energy and subsequently
      enlarges the nanostructure of the silica matrix to produce porous channels that
      cause the drug to be released easily. By taking these magnetic-responsive
      controllable drug release behaviors, the magnetic silica nanospheres can be
      designed for controlled burst release of therapeutic agents for especially urgent
      physiological needs.

PMID- 18052082
TI  - Model of drug-loaded fluorocarbon-based micelles studied by electron-spin induced
      (19)f relaxation NMR and molecular dynamics simulation.
AB  - Rf-IPDU-PEGs belong to a class of fluoroalkyl-ended poly(ethylene glycol)
      polymers (Rf-PEGs), where the IPDU (isophorone diurethane) functions as a linker
      to connect each end of the PEG chain to a fluoroalkyl group. The Rf-IPDU-PEGs
      form hydrogels in water with favorable sol-gel coexistence properties. Thus, they
      are promising for use as drug delivery agents. In this study, we introduce an
      electron-spin induced 19F relaxation NMR technique to probe the location and drug
      loading capacity for an electron-spin labeled hydrophobic drug, CT (chlorambucil
      tempol adduct), enclosed in the Rf-IPDU-PEG micelle. With the assistance of
      molecular dynamics simulations, a clear idea regarding the structures of the Rf
      IPDU-PEG micelle and its CT-loaded micelle was revealed. The significance of this
      research lies in the finding that the hydrophobic drug molecules were loaded
      within the intermediate IPDU shells of the Rf-IPDU-PEG micelles. The molecular
      structures of IPDU and that of CT are favorably comparable. Consequently, it
      appears that this study opens a window to modify the linker between the Rf group
      and the PEG chain for achieving customized structure-based drug-loading
      capabilities for these hydrogels, while the advantage of the strong affinity
      among the Rf groups to hold individual micelles together and to interconnect the
      micellar network is still retained in hopes of maintaining the sol-gel
      coexistence of the Rf-PEGs.

PMID- 18052084
TI  - Direct electrical measurements on single-molecule genomic DNA using single-walled
      carbon nanotubes.
AB  - A unique nanoelectronic platform, based on single-walled carbon nanotubes
      (SWNTs), has been fabricated for measuring electrical transport in single
      molecule DNA. We have tested 80 base pairs of single- and double-stranded DNA
      (ssDNA and dsDNA, respectively) of complex base sequences. About a 25-40 pA
      current (at 1 V) was measured for the dsDNA molecule covalently attached to the
      SWNT electrode at its termini. In the absence of base pair stacking, a ssDNA
      carries a feeble current of approximately 1 pA or less. Gate-voltage-dependent I
      V characteristics revealed that the bridging dsDNA molecule acts as a p-type
      channel between SWNT source and drain electrodes.

PMID- 18052083
TI  - Tunable resistive m-dPEG acid patterns on polyelectrolyte multilayers at
      physiological conditions: template for directed deposition of biomacromolecules.
AB  - This paper describes a new class of salt-responsive poly(ethylene glycol) (PEG)
      self-assembled monolayers (SAMs) on top of polyelectrolyte multilayer (PEMs)
      films. PEM surfaces with poly(diallyldimethylammonium chloride) as the topmost
      layer are chemically patterned by microcontact printing (muCP) oligomeric PEG
      molecules with an activated carboxylic acid terminal group (m-dPEG acid). The
      resistive m-d-poly(ethylene glycol) (m-dPEG) acid molecules on the PEMs films
      were subsequently removed from the PEM surface with salt treatment, thus
      converting the nonadhesive surfaces into adhesive surfaces. The resistive PEG
      patterns facilitate the directed deposition of various macromolecules such as
      polymers, dyes, colloidal particles, proteins, liposomes, and nucleic acids.
      Further, these PEG patterns act as a universal resist for different types of
      cells (e.g., primary cells, cell lines), thus permitting more flexibility in
      attaching a wide variety of cells to material surfaces. The patterned films were
      characterized by optical microscopy and atomic force microscopy (AFM). The PEG
      patterns were removed from the PEM surface at certain salt conditions without
      affecting the PEM films underneath the SAMs. Removal of the PEG SAMs and the
      stability of the PEM films underneath it were characterized with ellipsometry and
      optical microscopy. Such salt- and pH-responsive surfaces could lead to
      significant advances in the fields of tissue engineering, targeted drug delivery,
      materials science, and biology.

PMID- 18052085
TI  - Commentary: bioavailability of flavonoids and polyphenols: call to arms.

PMID- 18052086
TI  - Metabolism and bioavailability of flavonoids in chemoprevention: current
      analytical strategies and future prospectus.
AB  - Flavonoids are structurally diverse and among the most ubiquitous groups of
      dietary polyphenols distributed in various fruits and vegetables. Many have been
      proposed to be bioactive compounds in the diet that are responsible for lowering
      the risk of cancer and have been used in chemoprevention studies using animal
      models of this disease. As for any xenobiotic, to evaluate the potential risks
      and benefits of bioflavonoids to human health, an understanding of the
      physiological behavior of these compounds following oral ingestion is needed as
      well as their absorption, distribution, metabolism, and excretion (ADME). The
      study on metabolism and bioavailability is very important in defining the
      pharmacological and toxicological profile of these compounds. Due to great
      structural diversity among flavonoids, these profiles differ greatly from one
      compound to another, so that the most abundant polyphenols in our diet are not
      necessarily the ones that reach target tissues. Therefore, careful analysis of
      flavonoids and their metabolites in biological systems is critical. Mass
      spectrometry in various combinations with chromatographic methods has been a
      mainstay in applications that involve profiling and quantification of metabolites
      in complex biological samples. Because of its speed, sensitivity and specificity,
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the
      technology of choice for sample analysis. This review describes the chemistry of
      polyphenols and flavonoids, their ADME, and the various mass spectrometry-based
      strategies used in the analysis of flavonoids, including future trends in this
      field.

PMID- 18052088
TI  - On the intractability of estrogen-related receptor alpha as a target for
      activation by small molecules.
AB  - The estrogen-related receptor alpha (ERRalpha) is a potential target for
      activation in the treatment of metabolic disease. To date, no small-molecule
      agonists of ERRalpha have been identified despite several high-throughput
      screening campaigns. We describe the synthesis and profiling of a small array of
      compounds designed on the basis of a previously reported agonist-bound crystal
      structure of the closely related receptor ERRgamma. The results suggest that
      ERRalpha may be intractable as a direct target for pharmacologic activation.

PMID- 18052089
TI  - Facile stereospecific synthesis and biological evaluation of (S)- and (R)-2-amino
      2-methyl-4-[123I]iodo-3-(E)-butenoic acid for brain tumor imaging with single
      photon emission computerized tomography.
AB  - Both enantiomers of 2-amino-2-methyl-4-iodo-3-(E)-butenoic acid (IVAIB, 5) were
      radioiodoinated in 65-72% yield. (S)-IVAIB entered 9L gliosarcoma cells primarily
      via A-type transport in vitro with higher uptake than (R)-IVAIB. Biodistribution
      studies in rats with 9L gliosarcoma brain tumors demonstrated higher tumor to
      brain ratios with (S)-IVAIB (75:1 at 1 h) than (R)-IVAIB (7.7:1). In this model,
      (S)-IVAIB is superior to (R)-IVAIB and is a promising radiotracer for brain tumor
      imaging.

PMID- 18052087
TI  - Disposition of flavonoids via enteric recycling: enzyme stability affects
      characterization of prunetin glucuronidation across species, organs, and UGT
      isoforms.
AB  - We characterized the in vitro glucuronidation of prunetin, a prodrug of genistein
      that is a highly active cancer prevention agent. Metabolism studies were
      conducted using expressed human UGT isoforms and microsomes/S9 fractions prepared
      from intestine and liver of rodents and humans. The results indicated that human
      intestinal microsomes were more efficient than liver microsomes in
      glucuronidating prunetin, but rates of metabolism were dependent on time of
      incubation at 37 degrees C. Human liver and intestinal microsomes mainly produced
      metabolite 1 (prunetin-5- O-glucuronide) and metabolite 2 (prunetin-4'- O
      glucuronide), respectively. Using 12 human UGT isoforms, we showed that UGT1A7,
      UGT1A8, and UGT1A9 were mainly responsible for the formation of metabolite 1,
      whereas UGT1A1, UGT1A8, and UGT1A10 were mainly responsible for the formation of
      metabolite 2. This isoform-specific metabolism was consistent with earlier
      results obtained using human liver and intestinal microsomes, as the former
      (liver) is UGT1A9-rich whereas the latter is UGT1A10-rich. Surprisingly, we found
      that the thermostability of the microsomes was isoform- and organ-dependent. For
      example, human liver microsomal UGT activities were much more heat-stable (37
      degrees C) than intestinal microsomal UGT activities, consistent with the finding
      that human UGT1A9 is much more thermostable than human UGT1A10 and UGT1A8. The
      organ-specific thermostability profiles were also evident in rat microsomes and
      mouse S9 fractions, even though human intestinal glucuronidation of prunetin
      differs significantly from rodent intestinal glucuronidation. In conclusion,
      prunetin glucuronidation is species-, organ-, and UGT-isoform-dependent, all of
      which may be impacted by the thermostability of specific UGT isoforms involved in
      the metabolism.

PMID- 18052091
TI  - Influence of nitrogen and sulfur on biomass production and carotenoid and
      glucosinolate concentrations in watercress (Nasturtium officinale R. Br.).
AB  - Watercress (Nasturtium officinale R. Br.) is a perennial herb rich in the
      secondary metabolites of glucosinolates and carotenoids. 2-phenethyl
      isothiocyanate, the predominate isothiocyanate hydrolysis product in watercress,
      can reduce carcinogen activation through inhibition of phase I enzymes and
      induction of phase II enzymes. Sulfur (S) and nitrogen (N) have been shown to
      influence concentrations of both glucosinolates and carotenoids in a variety of
      vegetable crops. Our research objectives were to determine how several levels of
      N and S fertility interact to affect watercress plant tissue biomass production,
      tissue C/N ratios, concentrations of plant pigments, and glucosinolate
      concentrations. Watercress was grown using nutrient solution culture under a
      three by three factorial arrangement, with three S (8, 16, and 32 mg/L) and three
      N (6, 56, and 106 mg/L) fertility concentrations. Watercress shoot tissue
      biomass, tissue %N, and tissue C/N ratios were influenced by N but were
      unaffected by changes in S concentrations or by the interaction of NxS. Tissue
      pigment concentrations of beta-carotene, lutein, 5,6-epoxylutein, neoxanthin,
      zeaxanthin, and the chlorophyll pigments responded to changes in N treatment
      concentrations but were unaffected by S concentrations or through N x S
      interactions. Watercress tissue concentrations of aromatic, indole, and total
      glucosinolate concentrations responded to changes in N treatments; whereas
      aliphatic, aromatic, and total glucosinolates responded to changes in S treatment
      concentrations. Individual glucosinolates of glucobrassicin, 4
      methoxyglucobrassicin, and gluconasturriin responded to N fertility treatments,
      while gluconapin, glucobrassicin, and gluconasturiin responded to changes in S
      fertility concentrations. Increases in carotenoid and glucosinolate
      concentrations through fertility management would be expected to influence the
      nutritional value of watercress in human diets.

PMID- 18052090
TI  - 2-(2'-((dimethylamino)methyl)-4'-(fluoroalkoxy)-phenylthio)benzenamine
      derivatives as serotonin transporter imaging agents.
AB  - A novel series of ligands with substitutions at the 5-position on phenyl ring A
      and at the 4'-position on phenyl ring B of 2-(2'-((dimethylamino)methyl)-4'
      (fluoroalkoxy)phenylthio)benzenamine (4'-2-fluoroethoxy derivatives 28-31 and 4'
      3-fluoropropoxy derivatives 40-42) were prepared and tested as serotonin
      transporter (SERT) imaging agents. The new ligands displayed high binding
      affinities to SERT (Ki ranging from 0.03 to 1.4 nM). The corresponding 18F
      labeled compounds, which can be prepared readily, showed excellent brain uptake
      and retention after iv injection in rats. The hypothalamus region showed high
      uptake values between 0.74% and 2.2% dose/g at 120 min after iv injection.
      Significantly, the hypothalamus to cerebellum ratios (target to nontarget ratios)
      at 120 min were 7.8 and 7.7 for [18F]28 and [18F]40, respectively. The selective
      uptake and retention in the hypothalamus, which has a high concentration of SERT
      binding sites, demonstrated that [18F]28 and [18F]40 are promising positron
      emission computed tomography imaging agents for mapping SERT binding sites in the
      brain.

PMID- 18052092
TI  - Kinetics of molecular encapsulation of 1-methylcyclopropene into alpha
      cyclodextrin.
AB  - 1-methylcyclopropene (1-MCP), an ethylene inhibiting regulator, is commercially
      available in the form of an inclusion complex with alpha-cyclodextrin (alpha-CD).
      In this study, molecular encapsulation of gaseous 1-MCP into aqueous alpha-CD was
      investigated in a closed, agitated vessel with a flat gas-liquid interface.
      Molecular encapsulation of gaseous 1-MCP by alpha-CD is a simultaneous two-step
      reaction which involves the aqueous dissolution of gaseous 1-MCP and the
      encapsulation of the dissolved molecules by alpha-CD. The kinetics and mechanism
      of molecular encapsulation were analyzed based on the depletion rate of 1-MCP in
      the headspace of the vessel. The encapsulation rates could be explained
      quantitatively by the gas absorption theory with a pseudo-first-order reaction
      between 1-MCP and alpha-CD. The negative value of the calculated apparent
      activation energy of encapsulation (-24.4 kJ/mol) implied the significant effect
      of exothermic aqueous dissolution of 1-MCP. An encapsulation temperature of 15
      degrees C was optimal; at this temperature, the highest 1-MCP yield and best
      inclusion ratio of inclusion complex were obtained. Changes in the X-ray
      diffraction pattern suggested that the crystal lattice structure of alpha-CD was
      altered upon inclusion of 1-MCP.

PMID- 18052093
TI  - Characterization of terpenoid volatiles from cultivars of eastern hemlock (Tsuga
      canadensis).
AB  - The volatile terpenoid fraction from needles in 13 cultivars of Tsuga canadensis
      L. (Carriere) was analyzed by gas chromatography with mass spectrometry (GC-MS).
      The results of this study are considered along with previously reported results
      for foliar terpenoid levels of the Asian (T. sieboldii, T. chinensis, T.
      diversifolia), western North American (T. mertensiana, T. heterophylla), and
      eastern North American species (T. canadensis, T. caroliniana) of hemlock to draw
      conclusions about the potential of cultivar host resistance to the hemlock woolly
      adelgid (Adelges tsugae Annand). It is suggested that hemlocks in eastern North
      America have adapted their terpenoid chemistry for protection against endemic
      defoliators and that this has made them vulnerable to non-native, sucking pests
      such as adelgids and scales. Some cultivars of T. canadensis have a terpenoid
      profile that resembles that of the resistant noneastern North American species
      and are candidates for biological screening for resistance. Among the cultivars,
      the variation in terpenoid chemistry did not absolutely correspond with the
      considerable differences in morphological characters observed, indicating that
      the terpenoid chemistry is not definitively coupled with hemlock morphology.

PMID- 18052094
TI  - Selenium and aflatoxin levels in raw Brazil nuts from the Amazon basin.
AB  - Whereas selenium (Se) is an important antioxidant in human metabolism to prevent
      cancer, aflatoxins are highly carcinogenic. Brazil nuts from Eastern and Western
      Amazon regions were evaluated to find any relationship between Se and aflatoxins
      levels. A total of 80 (in-shell and shelled) nuts samples were collected directly
      from different forest sites and analyzed for Se by atomic emission spectrometry
      and aflatoxins by liquid chromatography tandem mass spectrometry. The limit of
      quantitation (LOQ) for Se was 2.0 mg/kg, and LOQ for total aflatoxins was 0.390
      microg/kg. Nut Se levels from the Eastern region were higher than the Western, in
      addition to the aflatoxins. The moisture content (mc) and water activity (aw) of
      the raw nuts from the two regions did not present a significant difference, for
      either in-shell or shelled. The mc was 24.5% (minimum of 20.1% and maximum of
      30.4%) and 22.1% (minimum of 14.6% and maximum of 28.9%) and a w of 0.85 for both
      regions. Further studies need to be carried out to discover the role of Se on
      fungi growth stress and aflatoxin production mechanisms.

PMID- 18052095
TI  - Ion-trap tandem mass spectrometry for the analysis of polychlorinated dibenzo-p
      dioxins, dibenzofurans, and dioxin-like polychlorinated biphenyls in food.
AB  - This paper reports on the applicability of gas chromatography coupled to ion-trap
      tandem mass spectrometry (GC/ITMS/MS) for the analysis of polychlorinated dibenzo
      p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxin-like polychlorinated
      biphenyls (dl-PCBs) in food. MS/MS parameters were selected to achieve the high
      sensitivity and selectivity required for food analysis. Good precision (RSD=5-18%
      for PCDD/Fs and 6-14% for dl-PCBs) and low limits of detection for PCDD/Fs (0.1
      0.93 pg/g of fat) and dl-PCBs (0.1-0.89 pg/g of fat) were obtained. A comparative
      study of the congener-specific determination using both GC/ITMS/MS and GC-high
      resolution mass spectrometry (GC/HRMS) was performed by analyzing several
      matrices such as milk, fish oil, chicken, pork, fish, eggs, and a chicken
      compound feed, at low pg/g levels. The results using GC/ITMS/MS were in good
      agreement with those obtained by GC/HRMS. Consequently, GC/ITMS/MS is proposed
      for the analysis of PCDD/Fs and dl-PCBs in food and feed samples.

PMID- 18052096
TI  - Multienzyme inhibition assay for residue analysis of insecticidal
      organophosphates and carbamates.
AB  - A recently developed spectrophotometric assay for the detection of
      organophosphorus and carbamate insecticides by means of cutinase inhibition has
      been successfully extended to two esterases derived from Bacillus subtilis (BS2)
      and rabbit liver. These esterases were selected because of their high sensitivity
      to the examined insecticide classes and their pronounced inhibition profile. With
      inhibition constants (ki) of 2.0x10(7) and 2.6x10(6) L/(mol.min) for rabbit liver
      esterase and BS2, respectively, chlorpyrifos oxon proved to be the strongest
      inhibitor directly followed by paraoxon. As compared to choline esterases and the
      recently studied cutinase, both esterases are surprisingly strongly inhibited by
      organophosphorus thions, showing k i in the range of 5.3x10(2) to 2.3x10(4)
      L/(mol.min). All tested insecticidal carbamates were also inhibitors of BS2 and
      rabbit liver esterase, albeit in a rather uniform manner. Generally, both enzymes
      were found to be about 2 orders of magnitude more sensitive on the studied
      insecticides than cutinase even with an enhanced sensitivity against plant matrix
      effects. Plant extracts, obtained according to the QuEChERS method, were
      subjected to solid-phase extraction (SPE) using a mixed mode strong anion
      exchanger/primary secondary amine sorbent and C18endcapped cartridges for
      superior cleanup. With spiked samples of apple juice, best recoveries of 73% (+/
      61%), 94% (+/-25%), and 134% (+/-17%) were obtained for chlorpyrifos, parathion
      methyl, and paraoxon, respectively. Results of exemplarily performed liquid
      chromatography-mass spectrometry control measurements were well in accordance
      with measurements obtained by enzyme inhibition.

PMID- 18052097
TI  - Suppressive effect of a proanthocyanidin-rich extract from longan (Dimocarpus
      longan Lour.) flowers on nitric oxide production in LPS-stimulated macrophage
      cells.
AB  - Anthocyanidins found in certain flowers have been shown to act as strong
      antioxidants in various systems, exhibiting multiple biological actions. The
      antioxidative effects of water extract and ethanolic extract of longan
      (Dimocarpus longan Lour.) flowers were evaluated by radical scavenging activity
      and compared to those of gallic acid, myricetin, and epigallocatechin gallate. In
      this study, the suppressive effects of longan flower extracts on nitric oxide and
      prostaglandin E2 production were investigated using a lipopolysaccharide
      stimulated RAW 264.7 cell model. Abundant levels of phenolic compounds including
      flavonoids, condensed tannins, and proanthocyanidins were found in water or
      ethanolic extracts prepared from dried longan flowers. The antioxidative effect
      of longan flower extract was similar to the effect exhibited by pure
      antioxidants. Moreover, longan flower extract showed prominent inhibitory effects
      on prostaglandin E2 production. Significant concentration-dependent inhibition of
      nitric oxide production was detected when cells were cotreated with
      lipopolysaccharide and various concentrations of longan flower extracts. These
      inhibitory effects were further attributed to suppression of inducible nitric
      oxide synthase protein expression and not to reduced enzymatic activity. These
      results suggest that longan flower crude extracts, especially ethanolic extract,
      have antioxidant and anti-inflammatory effects, and the probable mechanism
      involves inhibition of inflammation by proanthocyanidins. Preliminary
      observations suggest that longan flower extract, especially alcoholic extract,
      could be another potential source of natural dietary antioxidant and anti
      inflammatory agent.

PMID- 18052098
TI  - Synthesis, herbicidal activities, and 3D-QSAR of 2-cyanoacrylates containing
      aromatic methylamine moieties.
AB  - A series of novel 2-cyanoacrylates containing different aromatic rings were
      synthesized, and their structures were characterized by (1)H NMR, elemental
      analysis, and single-crystal X-ray diffraction analysis. Their herbicidal
      activities against four weeds and inhibition of photosynthetic electron transport
      against isolated chloroplasts (the Hill reaction) were evaluated. Both in vivo
      and in vitro data showed that the compounds containing benzene, pyridine, and
      thiazole moieties gave higher activities than those containing pyrimidine,
      pyridazine, furan, and tetrahedronfuran moieties. To further explore the
      comprehensive structure-activity relationship on the basis of in vitro data,
      comparative molecular field analysis (CoMFA) was performed, and the results
      showed that a bulky and electronegative group around the para-position of the
      aromatic rings would have the potential for higher activity, which offered
      important structural insights into designing highly active compounds prior to the
      next synthesis.

PMID- 18052099
TI  - Beta-carotene isomer composition of sub- and supercritical carbon dioxide
      extracts. Antioxidant activity measurement.
AB  - In the present work sub- and supercritical extraction conditions using carbon
      dioxide were studied in order to obtain extracts with different compositions from
      the green microalgae Dunaliella salina. Different compositions of beta-carotene
      isomers were identified in the extracts by using HPLC-DAD. Also, antioxidant
      activity of the extracts was measured using a TEAC assay. An experimental design
      was applied considering two factors, extraction pressure and temperature, in a
      wide range of values, trying to maximize the extraction yield. Higher yields were
      obtained at high pressures and low temperatures, that is, at higher CO2
      densities. Attempts were made to correlate the antioxidant activity of the
      extracts with their chemical composition by means of principal component
      analysis. A certain relationship was found between their antioxidant activity and
      the isomeric composition of beta-carotenes. As a result, an original equation is
      proposed to predict the antioxidant activity of extracts from D. salina in terms
      of the ratio 9-cis-beta-carotene/all-trans-beta-carotene, the concentration of
      alpha-carotene, and, especially, the concentration of 9-cis-beta-carotene.

PMID- 18052100
TI  - Development of a real-time PCR method to detect potentially allergenic sesame
      (Sesamum indicum) in food.
AB  - Recent papers indicate that the prevalence of allergic reactions to sesame
      (Sesamum indicum) is increasing in European countries. This paper describes the
      development of a selective real-time PCR method for the detection of sesame in
      food. The assay did not show any cross-reactivity with 17 common food
      ingredients. The real-time PCR method was applied to determine sesame in several
      crackers, salty snacks, biscuits, tahina sesame paste and sesame oil. With the
      exception of sesame oil, in all of the samples where sesame was declared, sesame
      was detected by the real-time PCR assay (Ct value<35). In the samples which might
      contain sesame or where sesame was not listed, sesame could not be detected (Ct
      value>35).

PMID- 18052101
TI  - Determination of postharvest fungicides in fruit juices by solid-phase extraction
      followed by liquid chromatography electrospray time-of-flight mass spectrometry.
AB  - A multiresidue method using liquid chromatography-time-of-flight mass
      spectrometry (LC-TOFMS) has been developed for the quantitative analysis of five
      widely used postharvest fungicides (carbendazim, thiabendazole, imazalil,
      prochloraz, and iprodione) and two of their transformation products (imazalil and
      prochloraz metabolites) in fruit juices. LC-TOFMS in positive electrospray
      ionization mode was used to quantify and confirm trace levels of these fungicides
      in fruit juices. The proposed method consists of a sample treatment step based on
      solid-phase extraction using hydrophilic-lipophilic-balanced polymer-based
      reverse-phase SPE cartridges (Oasis HLB) and methanol as an eluting solvent.
      Fruit-juice extracts spiked at different fortification levels (10 and 20 microg
      L(-1)) yielded average recoveries in the range of 71-109% with RSD (%) below 15%.
      Subsequent identification, confirmation, and quantitation were carried out by LC
      TOFMS analysis. The confirmation of the target species was based on accurate mass
      measurements of protonated molecules ([M+H]+) and fragment ions, obtaining
      routine accuracy errors lower than 2 ppm in most cases. The obtained limits of
      detection (LODs) of the proposed method were in the range of 0.08-0.45 microg L(
      1). Finally, the proposed method was successfully applied to the analysis of 23
      fruit juice samples collected from different European countries and the United
      States, showing the potential applicability of the method in routine analysis.
      Over 50% of the samples tested contained pesticide residues, but relatively low
      concentration levels were found.

PMID- 18052102
TI  - Determination of water-soluble polyphenolic compounds in commercial herbal teas
      from Lamiaceae: peppermint, melissa, and sage.
AB  - Chromatographic techniques (HPLC and HPTLC) were used for qualitative and
      quantitative determination of eriocitrin, luteolin 7-O-rutinoside, luteolin 7-O
      beta-glucuronide, lithospermic acid, rosmarinic acid, and methyl rosmarinate
      together with other known compounds in commercial herbal teas from the Lamiaceae
      family: peppermint leaf (Menthae piperitae folium), melissa leaf (Melissae
      folium), and sage leaf (Salviae officinalis folium). Contents of analyzed
      compounds in infusions, the most popular forms, were established using a C18
      column with acetonitrile-water-formic acid as a mobile phase. The HPLC method was
      validated for linearity, precision, and accuracy. Luteolin 7-O-beta-glucuronide
      and lithospermic acid were identified as new Mentha x piperita compounds. The
      investigated herbal teas delivered polyphenols in high amounts, up to 182.2 mg
      for the infusion of one peppermint tea bag.

PMID- 18052104
TI  - Idiosyncratic drug reactions: past, present, and future.
AB  - Although the major working hypothesis for the mechanism of idiosyncratic drug
      reactions (IDRs), the hapten hypothesis, has not changed since 1987, several
      hypotheses have been added, for example, the danger hypothesis and the
      pharmaceutical interaction hypothesis. Genetic studies have found that several
      IDRs are linked to specific HLA genes, providing additional evidence that they
      are immune-mediated. Evidence that most IDRs are caused by reactive metabolites
      has led pharmaceutical companies to avoid drug candidates that form significant
      amounts of reactive metabolites; however, at least one IDR, ximelagatran-induced
      liver toxicity, does not appear to be caused by a reactive metabolite. It is
      possible that there are biomarkers such as those related to cell stress that
      would predict that a drug candidate would cause a significant incidence of IDRs;
      however, there has been no systematic study of the changes in gene expression
      induced by drugs known to cause IDRs. A major impediment to the study of the
      mechanisms of IDRs is the paucity of valid animal models, and if we had a better
      mechanistic understanding, it should be easier to develop such models. There is
      growing evidence that these adverse reactions are more varied and complex than
      previously recognized, and it is unlikely that a quick fix will be achieved.
      However, IDRs are an important cause of patient morbidity and mortality and
      markedly increase the uncertainty of drug development; therefore, continued basic
      research in this area is essential.

PMID- 18052103
TI  - Progress and challenges in selected areas of tobacco carcinogenesis.
AB  - Tobacco use continues to be a major cause of cancer in the developed world, and
      despite significant progress in this country in tobacco control, which is driving
      a decrease in cancer mortality, there are still over 1 billion smokers in the
      world. This perspective discusses some selected issues in tobacco carcinogenesis
      focusing on progress during the 20 years of publication of Chemical Research in
      Toxicology. The topics covered include metabolism and DNA modification by tobacco
      specific nitrosamines, tobacco carcinogen biomarkers, an unidentified DNA
      ethylating agent in cigarette smoke, mutations in the K-RAS and p53 gene in
      tobacco-induced lung cancer and their possible relationship to specific
      carcinogens, secondhand smoke and lung cancer, emerging issues in smokeless
      tobacco use, and a conceptual model for understanding tobacco carcinogenesis. It
      is hoped that a better understanding of mechanisms of tobacco-induced cancer will
      lead to new and useful approaches for the prevention of lung cancer and other
      cancers caused by tobacco use.

PMID- 18052105
TI  - Potential mechanisms of estrogen quinone carcinogenesis.
AB  - There is a clear association between the excessive exposure to estrogens and the
      development of cancer in hormone-sensitive tissues (breast, endometrium). It has
      become clear that there are likely multiple overlapping mechanisms of estrogen
      carcinogenesis. One major pathway is the extensively studied hormonal pathway, by
      which estrogen stimulates cell proliferation through nuclear estrogen receptor
      (ER)-mediated signaling, thus resulting in an increased risk of genomic mutations
      during DNA replication. A similar "nongenomic pathway", potentially involving
      newly discovered membrane-associated ERs, also appears to regulate extranuclear
      estrogen signaling pathways. This perspective is focused on a third pathway
      involving the metabolism of estrogens to catechols mediated by cytochrome P450
      and further oxidation of these catechols to estrogen o-quinones. Oxidative
      enzymes, metal ions, and in some cases molecular oxygen can catalyze o-quinone
      formation, so that these electrophilic/redox-active quinones can cause damage
      within cells by alkylation and/or oxidation of cellular proteins and DNA in many
      tissues. It appears that the endogenous estrogen quinones primarily form unstable
      N3-adenine or N7-guanine DNA adducts, ultimately resulting in mutagenic apurinic
      sites. In contrast, equine estrogen quinones, formed from estrogens present in
      popular hormone replacement therapy prescriptions, generate a variety of DNA
      lesions, including bulky stable adducts, apurinic sites, DNA strand cleavage, and
      oxidation of DNA bases. DNA damage induced by these equine quinones is
      significantly increased in cells containing ERs, leading us to hypothesize a
      mechanism involving ER binding/alkylation by the catchol/quinone, resulting in a
      "Trojan horse". The "Trojan horse" carries the highly redox-active catechol to
      estrogen -sensitive genes, where high amounts of reactive oxygen species are
      generated, causing selective DNA damage. Our data further suggest that other key
      protein targets for estrogen o-quinones could be redox-sensitive enzymes (i.e,
      GST P1-1, QR). These proteins are involved in stress response cascades that are
      known to contribute to the regulation of cell proliferation and apoptosis.
      Finally, it has been shown that catechol estrogens can transform breast
      epithelial cells into a tumorigenic phenotype and that these transformed cells
      had differential gene expression of several genes involved in oxidative stress.
      Given the direct link between excessive exposure to estrogens, metabolism of
      estrogens, and increased risk of breast cancer, it is crucial that factors that
      affect the formation, reactivity, and cellular targets of estrogen quinoids be
      thoroughly explored.

PMID- 18052107
TI  - Oxidative stress and neurotoxicity.
AB  - There is increasing awareness of the ubiquitous role of oxidative stress in
      neurodegenerative disease states. A continuing challenge is to be able to
      distinguish between oxidative changes that occur early in the disease from those
      that are secondary manifestations of neuronal degeneration. This perspective
      highlights the role of oxidative stress in Alzheimer's, Parkinson's, and
      Huntington's diseases, amyotrophic lateral sclerosis, and multiple sclerosis,
      neurodegenerative and neuroinflammatory disorders where there is evidence for a
      primary contribution of oxidative stress in neuronal death, as opposed to other
      diseases where oxidative stress more likely plays a secondary or by-stander role.
      We begin with a brief review of the biochemistry of oxidative stress as it
      relates to mechanisms that lead to cell death, and why the central nervous system
      is particularly susceptible to such mechanisms. Following a review of oxidative
      stress involvement in individual disease states, some conclusions are provided as
      to what further research should hope to accomplish in the field.

PMID- 18052108
TI  - 15-Deoxy-Delta(12,14)-prostaglandin J2: an electrophilic trigger of cellular
      responses.
AB  - Electrophilic molecules are endogenously generated and are causally involved in
      many pathophysiological effects. Prostaglandin D (20 (PGD (2)), a major
      cyclooxygenase product in a variety of tissues, readily undergoes dehydration to
      yield the cyclopentenone-type PGs of the J (2)-series such as 15-deoxy-Delta
      (12,14)-PGJ (2) (15d-PGJ (2)). 15d-PGJ (2) is an electrophile, which can
      covalently react via the Michael addition reaction with nucleophiles, such as the
      free sulfhydryls of glutathione and cysteine residues in cellular proteins that
      play an important role in the control of the redox cell-signaling pathways.
      Covalent binding of 15d-PGJ (2) to cellular proteins may be one of the mechanisms
      by which 15d-PGJ (2) induces a cellular response involved in most of the
      pathophysiological effects associated with inflammation. In the present
      perspective, we provide a comprehensive summary of 15d-PGJ (2) as an
      electrophilic mediator of cellular responses.

PMID- 18052106
TI  - Protein damage by reactive electrophiles: targets and consequences.
AB  - It has been 60 years since the Millers first described the covalent binding of
      carcinogens to tissue proteins. Protein covalent binding was gradually
      overshadowed by the emergence of DNA adduct formation as the dominant paradigm in
      chemical carcinogenesis but re-emerged in the early 1970s as a critical mechanism
      of drug and chemical toxicity. Technology limitations hampered the
      characterization of protein adducts until the emergence of mass spectrometry
      based proteomics in the late 1990s. The time since then has seen rapid progress
      in the characterization of the protein targets of electrophiles and the
      consequences of protein damage. Recent integration of novel affinity chemistries
      for electrophile probes, shotgun proteomics methods, and systems modeling tools
      has led to the identification of hundreds of protein targets of electrophiles in
      mammalian systems. The technology now exists to map the targets of damage to
      critical components of signaling pathways and metabolic networks and to
      understand mechanisms of damage at a systems level. The implementation of
      sensitive, specific analyses for protein adducts from both xenobiotic-derived and
      endogenous electrophiles offers a means to link protein damage to clinically
      relevant health effects of both chemical exposures and disease processes.

PMID- 18052110
TI  - Mechanism-based inactivation of human cytochromes p450s: experimental
      characterization, reactive intermediates, and clinical implications.
AB  - The P450 type cytochromes are responsible for the metabolism of a wide variety of
      xenobiotics and endogenous compounds. Although P450-catalyzed reactions are
      generally thought to lead to detoxication of xenobiotics, the reactions can also
      produce reactive intermediates that can react with cellular macromolecules
      leading to toxicity or that can react with the P450s that form them leading to
      irreversible (i.e., mechanism-based) inactivation. This perspective describes the
      fundamentals of mechanism-based inactivation as it pertains to P450 enzymes. The
      experimental approaches used to characterize mechanism-based inactivators are
      discussed, and the criteria required for a compound to be classified as a
      mechanism-based inactivator are outlined. The kinetic scheme for mechanism-based
      inactivation and the calculation of the relevant kinetic constants that describe
      a particular inactivation event are presented. The structural aspects and
      important functional groups of several classes of molecules that have been found
      to impart mechanism-based inactivation upon metabolism by P450s such as
      acetylenes, thiol-containing compounds that include isothiocyanates,
      thiazolidinediones, and thiophenes, arylamines, quinones, furanocoumarins, and
      cyclic tertiary amines are described. Emphasis throughout this perspective is
      placed on more recent findings with human P450s where the site of modification,
      whether it be the apoprotein or the heme moiety, and, at least in part, the
      identity of the reactive intermediate responsible for the loss in P450 activity
      are known or inferred. Recent advances in trapping procedures as well as new
      methods for identification of reactive intermediates are presented. A variety of
      clinically important drugs that act as mechanism-based inactivators of P450s are
      discussed. The irreversible inactivation of human P450s by these drugs has the
      potential for causing serious drug-drug interactions that may have severe
      toxicological effects. The clinical significance of inactivating human P450s for
      improving drug efficacy as well as drug safety is discussed along with the
      potential for exploiting mechanism-based inactivators of P450s for therapeutic
      benefits.

PMID- 18052109
TI  - DNA adduct structure-function relationships: comparing solution with polymerase
      structures.
AB  - It has now been nearly two decades since the first solution structures of DNA
      duplexes covalently damaged by metabolically activated polycyclic aromatic
      hydrocarbons and amines were determined by NMR. Dozens of such high-resolution
      structures are now available, and some broad structural themes have been
      uncovered. It has been hypothesized that the solution structures are relevant to
      the biochemical processing of the adducts. The structural features of the adducts
      are considered to determine their mutational properties in DNA polymerases and
      their repair susceptibilities. In recent years, a number of crystal structures of
      DNA adducts of interest to our work have been determined in DNA polymerases.
      Accordingly, it is now timely to consider how NMR solution structures relate to
      structures within DNA polymerases. The NMR solution structural themes for
      polycyclic aromatic adducts are often observed in polymerase crystal structures.
      While the polymerase interactions can on occasion override the solution
      preferences, intrinsic adduct conformations favored in solution are often
      manifested within polymerases and likely play a significant role in lesion
      processing.

PMID- 18052111
TI  - Metabolism and toxicity of drugs. Two decades of progress in industrial drug
      metabolism.
AB  - The science of drug metabolism and pharmacokinetics (DMPK) has developed
      significantly over the past 20 years, and its functional role in today's
      pharmaceutical industry has matured to the point where DMPK has become an
      indispensable discipline in support of drug discovery and development. While
      contributions to the lead optimization phase of discovery efforts have been
      particularly noteworthy in helping to select only the best drug candidates for
      entry into development, it should be recognized that the scope of DMPK spans the
      continuum of discovery through clinical evaluation and even into the post
      marketing phase; as such, the breadth of DMPK's involvement is almost unique in
      contemporary pharmaceutical research. This perspective summarizes notable
      advances in the field, many of which have been made possible by technological
      developments in areas such as molecular biology, genetics, and bioanalytical
      chemistry, and highlights the critical nature of key partnerships between Drug
      Metabolism, Medicinal Chemistry, and Safety Assessment groups in attempting to
      advance drug candidates with a low potential for causing adverse events in
      humans. Finally, some speculative predictions are made of the future role of DMPK
      in pharmaceutical research, where current advances in our mechanistic
      understanding of the molecular processes that control the absorption,
      disposition, metabolism, elimination, and toxicity of drugs and their
      biotransformation products will combine to further enhance the impact of DMPK in
      drug discovery and development.

PMID- 18052112
TI  - The chemical toxicology of 2-deoxyribose oxidation in DNA.
AB  - Damage to DNA and RNA caused by oxidative mechanisms has been well-studied for
      its potential role in the development of human disease. Only recently, though,
      have we begun to appreciate that oxidation of the 2-deoxyribose moiety in DNA is
      also a determinant of the genetic toxicology of oxidative stress and
      inflammation, with involvement in more than just "strand breaks", such as complex
      DNA lesions, protein-DNA cross-links, and protein and DNA adducts. As an update
      to a 1992 review of 2'-deoxyribose oxidation by bleomycin and the enediynes
      published in Chemical Research in Toxicology [Dedon, P. C., and Goldberg, I. H.
      (1992) Chem. Res. Toxicol. 5, 311-332], this review focuses on recent
      developments in the chemical biology, bioanalytical chemistry, and genetic
      toxicology of 2-deoxyribose oxidation products in DNA under biologically relevant
      conditions.

PMID- 18052113
TI  - Identifying the structural requirements for chromosomal aberration by
      incorporating molecular flexibility and metabolic activation of chemicals.
AB  - Modeling the potential of chemicals to induce chromosomal damage has been
      hampered by the diversity of mechanisms which condition this biological effect.
      The direct binding of a chemical to DNA is one of the underlying mechanisms that
      is also responsible for bacterial mutagenicity. Disturbance of DNA synthesis due
      to inhibition of topoisomerases and interaction of chemicals with nuclear
      proteins associated with DNA (e.g., histone proteins) were identified as
      additional mechanisms leading to chromosomal aberrations (CA). A comparative
      analysis of in vitro genotoxic data for a large number of chemicals revealed that
      more than 80% of chemicals that elicit bacterial mutagenicity (as indicated by
      the Ames test) also induce CA; alternatively, only 60% of chemicals that induce
      CA have been found to be active in the Ames test. In agreement with this
      relationship, a battery of models is developed for modeling CA. It combines the
      Ames model for bacterial mutagenicity, which has already been derived and
      integrated into the Optimized Approach Based on Structural Indices Set (OASIS)
      tissue metabolic simulator (TIMES) platform, and a newly derived model accounting
      for additional mechanisms leading to CA. Both models are based on the classical
      concept of reactive alerts. Some of the specified alerts interact directly with
      DNA or nuclear proteins, whereas others are applied in a combination of two- or
      three-dimensional quantitative structure-activity relationship models assessing
      the degree of activation of the alerts from the rest of the molecules. The use of
      each of the alerts has been justified by a mechanistic interpretation of the
      interaction. In combination with a rat liver S9 metabolism simulator, the model
      explained the CA induced by metabolically activated chemicals that do not elicit
      activity in the parent form. The model can be applied in two ways: with and
      without metabolic activation of chemicals.

PMID- 18052114
TI  - Advances in the enzymatic reduction of ketones.
AB  - Historically, biocatalytic ketone reductions involved the use of Baker's yeast.
      Within the last five years, a significant and growing number of isolated
      ketoreductases have become available that have rendered yeast-based reductions
      obsolete. The broad substrate range and exquisite selectivities of these enzymes
      repeatedly outperform other ketone reduction chemistries, making biocatalysis the
      general method of choice for ketone reductions. Presented here is a summary of
      our understanding of the capabilities and limitations of these enzymes.

PMID- 18052115
TI  - Modified "4 + 1" mixed ligand technetium-labeled fatty acids for myocardial
      imaging: evaluation of myocardial uptake and biodistribution.
AB  - Our group previously synthesized 99m Tc-labeled fatty acids suitable for
      myocardial metabolism and flow imaging. In this set of experiments, 29 new
      analogues were synthesized according to the "4 + 1" mixed ligand approach with
      some specific differences. Conventional "4 + 1" 99m Tc-fatty acids are built in
      the sequence: Tc-chelate, alkyl chain, and carboxylic group. We developed
      compounds following a new design with the sequence: carboxylic group, alkyl
      chain, Tc-chelate, and lipophilic tail. Therefore, the 99m Tc-chelate was
      transferred to a more central position of the compound, aiming toward an improved
      myocardial profile and an accelerated liver clearance. In this context, several
      functional groups incorporated in the lipophilic tail section were tested to
      evaluate their influence on the compound's character. In addition to
      biodistribution studies in vivo, the myocardial first-pass extraction of the
      compounds was tested in an isolated Langendorff rat heart model. A satisfactory
      myocardial uptake of up to 20% of the injected dose (% ID) in the perfused heart
      and a fast liver clearance in vivo with only 0.29% ID/g at 60 min postinjection
      demonstrate that the induced molecular modifications affect the kinetics of 99m
      Tc-radiolabeled fatty acid compounds favorably. From the data set, rules for
      estimating the biodistribution of fatty acids tracers are deduced.

PMID- 18052116
TI  - Amine-guanidine switch: a promising approach to improve DNA binding and
      antiproliferative activities.
AB  - A series of polyaromatic guanidino derivatives was synthesized and evaluated for
      growth inhibitory properties in several human carcinoma cell lines. The
      properties of these guanidino compounds were compared to those of their
      corresponding synthetic amino precursors. The size of the polyaromatic ring
      system as well as the length of the tether attached to the ring had a direct
      impact on the observed antiproliferative profiles, compound 14 having the
      broadest spectrum of activity. As both series intercalate DNA, guanidine
      derivatives showed a remarkable affinity for DNA and the guanidinium group
      appeared to be essential, yet not sufficient for caspase-3/7 activation. Compound
      14 also showed significant in vivo activity against breast cancer cell xenografts
      in NOG/SCID mice. These results suggest that the electronic nature of chain
      tethering an intercalator not only influences the DNA-binding process but also
      controls the antitumoral activity of the whole compound.

PMID- 18052117
TI  - Design and synthesis of human immunodeficiency virus entry inhibitors:
      sulfonamide as an isostere for the alpha-ketoamide group.
AB  - The crystal structures of many tertiary alpha-ketoamides reveal an orthogonal
      arrangement of the two carbonyl groups. Based on the hypothesis that the alpha
      ketoamide HIV attachment inhibitor BMS 806 (formally BMS378806, 26) might bind to
      its gp120 target via a similar conformation, we designed and synthesized a series
      of analogs in which the ketoamide group is replaced by an isosteric sulfonamide
      group. The most potent of these analogs, 14i, demonstrated antiviral potency
      comparable to 26 in the M33 pseudotyped antiviral assay. Flexible overlay
      calculations of a ketoamide inhibitor with a sulfonamide inhibitor revealed a
      single conformation of each that gave significantly better overlap of key
      pharmacophore features than other conformations and thus suggest a possible
      binding conformation for each class.

PMID- 18052118
TI  - Posterior error probabilities and false discovery rates: two sides of the same
      coin.
AB  - A variety of methods have been described in the literature for assigning
      statistical significance to peptides identified via tandem mass spectrometry.
      Here, we explain how two types of scores, the q-value and the posterior error
      probability, are related and complementary to one another.

PMID- 18052119
TI  - Integrated analysis of the cerebrospinal fluid peptidome and proteome.
AB  - Cerebrospinal fluid (CSF) is the only body fluid in direct contact with the brain
      and thus is a potential source of biomarkers. Furthermore, CSF serves as a medium
      of endocrine signaling and contains a multitude of regulatory peptides. A
      combined study of the peptidome and proteome of CSF or any other body fluid has
      not been reported previously. We report confident identification in CSF of 563
      peptide products derived from 91 precursor proteins as well as a high confidence
      CSF proteome of 798 proteins. For the CSF peptidome, we use high accuracy mass
      spectrometry (MS) for MS and MS/MS modes, allowing unambiguous identification of
      neuropeptides. Combination of the peptidome and proteome data suggests that
      enzymatic processing of membrane proteins causes release of their extracellular
      parts into CSF. The CSF proteome has only partial overlap with the plasma
      proteome, thus it is produced locally rather than deriving from plasma. Our work
      offers insights into CSF composition and origin.

PMID- 18052121
TI  - Metabolite profiling of two low phytic acid (lpa) rice mutants.
AB  - Two low phytic acid (lpa) rice mutant lines, Os-lpa-XS110-1 and Os-lpa-XS110-2,
      were grown together with their parent wild-type variety Xiushui 110 in four field
      trials. HPLC analysis of inositol phosphates in the seeds produced demonstrated
      that compared to the wild-type, the reduction in phytic acid content in Os-lpa
      XS110-1 (-46%) was more pronounced than that in Os-lpa-XS110-2 (-23%). Lower
      inositol phosphates (InsP 3, InsP 4, InsP 5) were not detected in the mutants.
      The lpa mutants and the wild-type rice were subjected to comparative metabolite
      profiling by capillary gas chromatography. On average, 34% (Os-lpa-XS110-1) and
      42% (Os-lpa-XS110-2) of the detected peaks were statistically significantly
      different between wild-type and mutants. However, only a few of these differences
      could be consistently observed for all field trials. Identification and
      quantification of the consistently different metabolites revealed that contents
      of myo-inositol and raffinose were increased in Os-lpa-XS110-1 but decreased in
      Os-lpa-XS110-2 compared to the wild-type. In addition, Os-lpa-XS110-1 exhibited
      increased levels of galactose and galactinol. Consideration of these metabolic
      changes in light of the routes involved in the biosynthesis of phytic acid
      indicated a disturbance in the early biosynthetic pathway of phytic acid in Os
      lpa-XS110-2 (similar to the lpa-1 type mutation in maize) and a mutation event
      affecting phosphorylation of myo-inositol in Os-lpa-XS110-1 (similar to the lpa-3
      type mutation).

PMID- 18052120
TI  - A data-mining scheme for identifying peptide structural motifs responsible for
      different MS/MS fragmentation intensity patterns.
AB  - Although tandem mass spectrometry (MS/MS) has become an integral part of
      proteomics, intensity patterns in MS/MS spectra are rarely weighted heavily in
      most widely used algorithms because they are not yet fully understood. Here a
      knowledge mining approach is demonstrated to discover fragmentation intensity
      patterns and elucidate the chemical factors behind such patterns. Fragmentation
      intensity information from 28 330 ion trap peptide MS/MS spectra of different
      charge states and sequences went through unsupervised clustering using a
      penalized K-means algorithm. Without any prior chemistry assumptions, four
      clusters with distinctive fragmentation patterns were obtained. A decision tree
      was generated to investigate peptide sequence motif and charge state status that
      caused these fragmentation patterns. This data-mining scheme is generally
      applicable for any large data sets. It bypasses the common prior knowledge
      constraints and reports on the overall peptide fragmentation behavior. It
      improves the understanding of gas-phase peptide dissociation and provides a
      foundation for new or improved protein identification algorithms.

PMID- 18052122
TI  - New approach for characterization of gelatin biopolymer films using proton
      behavior determined by low field 1H NMR spectrometry.
AB  - The behavior of protons in biopolymer films (BFs) formed with gelatin, water, and
      glycerol was investigated at various relative humidities (RHs) and concentrations
      of glycerol using a low field 1H NMR spectrometer. At a RH of approximately 0%,
      the distributed spin-spin relaxation times (T2) of protons in BFs showed two
      components: a rapidly relaxing proton with the shortest T2 derived from protons
      in the rigid backbone of the gelatin polymer such as CH1-, CH2-, and CH3-, and a
      slowly relaxing component with longer T2 from protons of the functional groups in
      amino acid residues in gelatin such as -OH, -COOH, and -NH3. These two components
      are referred to as nonexchangeable (T2N) and exchangeable protons (T2E),
      respectively, indicating the different mobility of the protons. The T2E increased
      as RH increased indicating the increase in relative mobility of protons due to
      the larger free volume in the BF matrix. Above a RH of 33%, the slowest relaxing
      component was found in all BFs and referred to as hydration-water protons (T2W)
      with the highest relative mobility of all protons in the films. It suggests that
      the free volume in BFs can be formed above a RH of 33% in the absence of
      glycerol. The behaviors of T2N, T2E, and T2W reveal the formation of free volume
      in the BF matrix associated with the presence of plasticizers (water and
      glycerol). The T2 behavior in BFs is consistent with the behavior of spin-lattice
      relaxation (T1). Our result is the first attempt to characterize using low field
      1H NMR technology how all protons in a film matrix behave and to develop
      correlations between proton mobility and free volume in protein-based BFs
      plasticized with water and glycerol.

PMID- 18052123
TI  - Synthesis and fungicidal activity of macrolactams and macrolactones with an oxime
      ether side chain.
AB  - Three series of novel macrolactams and macrolactones--12-alkoxyimino
      tetradecanlactam, 12-alkoxyiminopentadecanlactam, and 12-alkoxyiminodecanlactone
      derivatives (7A, 7B, and 7C)--were synthesized from corresponding 12
      oxomacrolactams and 12-oxomacrolactone. Their structures were confirmed by 1H NMR
      and elemental analysis. The Z and E isomers of 7A and 7B were separated, and
      their configurations were determined by 1H NMR. These compounds showed fair to
      excellent fungicidal activities against Rhizoctonia solani Kuhn. It is
      interesting that the Z and E isomers of most of the compounds have quite
      different fungicidal activities. The fact that the compounds have a gradual
      increase of fungicidal activity in the order of 7A, 7C, and 7B indicated that the
      macrocyclic derivatives with a hydrogen-bonding acceptor (=N-O-) and a hydrogen
      bonding donor (-CONH-) on the ring, and a three methylenes distance (CH2CH2CH2)
      between these two functional groups, exhibited the best fungicidal activity. The
      bioassay also showed that 7B not only has good fungicidal activity but also may
      have a broad spectrum of fungicidal activities.

PMID- 18052124
TI  - Cholesterol lowering mechanism of soybean protein hydrolysate.
AB  - Numerous attempts have been made to find the mechanism and component of the
      cholesterol lowering activity of soybean. In this study, it was proved that the
      peptides in soybean protein hydrolysate (SPH) made by certain proteases have a
      hypocholesterolemic effect. Among the mechanisms suggested, that is, blockage of
      bile acid and/or cholesterol absorption, inhibition of cholesterol synthesis, and
      stimulation of low-density lipoprotein receptor (LDL-R) transcription, SPH
      appeared to stimulate LDL-R transcription. When Hep T9A4 cells were incubated
      with soy protein hydrolysates by using the proteases from Bacillus
      amyloliquefaciens FSE-68, LDL-R transcription was strongly stimulated, but the
      other mechanisms were not affected. Among the six types of SPH, F1-15, hydrolyzed
      with the neutral protease to a degree of hydrolysis (DH) of 15%, showed the
      highest LDL-R transcription. The fractions of molecular weight of 200 and 3000 Da
      showed LDL-R transcription stimulating activity. The bioactivity is due to
      soybean peptides because the ethanol extract of soybean protein which contains
      isoflavones does not stimulate LDL-R transcription. In conclusion, dietary
      upregulation of LDL-R transcription by soybean may be consequent to an enhanced
      catabolism or a reduced synthesis of intracellular cholesterol. Therefore, we
      suggest that soy peptides can effectively stimulate LDL-R transcription in the
      human liver cell line and reduce blood cholesterol level.

PMID- 18052125
TI  - Partial shading of Cabernet Sauvignon and Shiraz vines altered wine color and
      mouthfeel attributes, but increased exposure had little impact.
AB  - Few studies have investigated the impact of vine shading on the sensory
      attributes of the resultant wine. This study examines the effects of canopy
      exposure levels on phenolic composition plus aroma, flavor, and mouthfeel aspects
      in wine. Wines were made from Cabernet Sauvignon and Shiraz grapes (Vitis
      vinifera L.) subjected to different levels of canopy exposure in a commercial
      vineyard in the Sunraysia region, Victoria, Australia. Canopy exposure treatments
      included control (standard vineyard practice), exposed (achieved with a foliage
      wire 600 mm above the top cordon), highly exposed (using a foliage wire with leaf
      plucking in the fruit zone), and shaded treatment (using 70% shade-cloth).
      Spectral and descriptive analyses showed that levels of anthocyanins, other
      phenolics, and perceived astringency were lower in wines made from shaded fruit;
      however, the reverse was generally not observed in wines of exposed and highly
      exposed fruit. Descriptive analysis also showed wines from the shaded fruit were
      different from other treatments for a number of flavor and aroma characters.
      These findings have implications for vineyard management practices.

PMID- 18052126
TI  - Proline and processing of spider silks.
AB  - Major ampullate (MAA) silks from a variety of spider species were collected by
      artificial silking that adjusted the samples to have similar breaking strains.
      Those silks are highly comparable in post-yield mechanical properties, but their
      supercontraction behaviors and initial moduli vary in large ranges and both
      correlate with the content of one amino acid, proline. These relationships, in
      combination with protein sequence data, support the hypothesis that the proline
      related motif, that is, GPGXX, may play a key role in silk. This also explains
      the interspecific variability of spider dragline silk. Moreover, MAA silks from
      three representative species were prepared in a range of processing conditions
      and their mechanical properties were compared. Our results indicate how chemical
      compositions, coupled with processing conditions, shape the mechanical properties
      of the spider silk.

PMID- 18052127
TI  - The shape and size distribution of crystalline nanoparticles prepared by acid
      hydrolysis of native cellulose.
AB  - The shape and size distribution of crystalline nanoparticles resulting from the
      sulfuric acid hydrolysis of cellulose from cotton, Avicel, and tunicate were
      investigated using transmission electron microscopy (TEM) and atomic force
      microscopy (AFM) as well as small- and wide-angle X-ray scattering (SAXS and
      WAXS). Images of negatively stained and cryo-TEM specimens showed that the
      majority of cellulose particles were flat objects constituted by elementary
      crystallites whose lateral adhesion was resistant against hydrolysis and
      sonication treatments. Moreover, tunicin whiskers were described as twisted
      ribbons with an estimated pitch of 2.4-3.2 microm. Length and width distributions
      of all samples were generally well described by log-normal functions, with the
      exception of tunicin, which had less lateral aggregation. AFM observation
      confirmed that the thickness of the nanocrystals was almost constant for a given
      origin and corresponded to the crystallite size measured from peak broadening in
      WAXS spectra. Experimental SAXS profiles were numerically simulated, combining
      the dimensions and size distribution functions determined by the various
      techniques.

PMID- 18052128
TI  - Collagen-DNA complex.
AB  - Previously presented models of collagen-DNA (7) and collagen-siRNA (8) complexes
      point to a general description of delivery systems and indicate to what specific
      topology that system should be equipped with to effectively deliver the gene into
      the living body via in vivo and in vitro injection. We focused our interest on
      the nature of collagen-DNA complex structure and the molecular and environmental
      determinants of the self-association processes of collagen with the presence of
      DNA. In this aspect, the self-association of collagen-DNA complex offers an
      opportunity to characterize a unique system, which may be related to the general
      mechanisms of self-association of fiber macromolecules by water bridges. For
      characterizing the collagen-DNA interaction, we used FTIR-ATR, NMR, and AFM
      experiments done on a separate collagen film, DNA film, and on the peptide-DNA
      aqueous solution. We demonstrate that collagen-DNA spontaneously forms self
      assembling complex systems in aqueous solution. Such self-association of the
      complex could be induced by electrostatic interactions between neutral collagen
      cylinders, having strong dipole moment, and negatively charged DNA cylinders. A
      final complex could be formed by hydrogen bonds between specified donor groups of
      collagen and phosphate acceptor groups of DNA. According to FTIR measurements, a
      collagen triple helix should not change global conformation during collagen-DNA
      complex formation.

PMID- 18052129
TI  - Sesquiterpene lactones from the roots of Ferula varia and their cytotoxic
      activity.
AB  - The ethyl acetate-soluble fraction from a MeOH extract of the roots of Ferula
      varia gave six new sesquiterpene lactones (1-6) and five known sesquiterpenes (7
      11). Their structures were established on the basis of spectroscopic evidence.
      The cytotoxic activities of 1-11 were evaluated against selected human cancer
      cell lines. Compound 4 showed significant selective cytotoxicity against
      multidrug-resistant cancer cells (KB-C2). The cytotoxicities of compounds 1, 3,
      5, 8, and 11 against KB-C2 cells were enhanced in the presence of nontoxic
      concentrations of colchicine.

PMID- 18052130
TI  - Allergic contact dermatitis--formation, structural requirements, and reactivity
      of skin sensitizers.
AB  - Contact allergy is caused by a wide range of chemicals after skin contact. Its
      clinical manifestation, allergic contact dermatitis (ACD), is developed upon
      repeated contact with the allergen. This perspective focuses on two areas that
      have yielded new useful information during the last 20 years: (i) structure
      activity relationship (SAR) studies of contact allergy based on the concept of
      hapten-protein binding and (ii) mechanistic investigations regarding activation
      of nonsensitizing compounds to contact allergens by air oxidation or skin
      metabolism. The second area is more thoroughly reviewed since the full picture
      has previously not been published. Prediction of the sensitizing capacity of a
      chemical is important to avoid outbreaks of ACD in the population. Much research
      has been devoted to the development of in vitro and in silico predictive testing
      methods. Today, no method exists that is sensitive enough to detect weak
      allergens and that is robust enough to be used for routine screening. To cause
      sensitization, a chemical must bind to macromolecules (proteins) in the skin.
      Expert systems containing information about the relationship between the chemical
      structure and the ability of chemicals to haptenate proteins are available.
      However, few designed SAR studies based on mechanistic investigations of
      prohaptens have been published. Many compounds are not allergenic themselves but
      are activated in the skin (e.g., metabolically) or before skin contact (e.g., via
      air oxidation) to form skin sensitizers. Thus, more basic research is needed on
      the chemical reactions involved in the antigen formation and the immunological
      mechanisms. The clinical importance of air oxidation to activate nonallergenic
      compounds has been demonstrated. Oxidized fragrance terpenes, in contrast to the
      pure terpenes, gave positive patch test reactions in consecutive dermatitis
      patients as frequently as the most common standard allergens. This shows the
      importance of using compounds to which people are exposed when screening for ACD
      in dermatology clinics.

PMID- 18052131
TI  - Layer-by-layer coated digitally encoded microcarriers for quantification of
      proteins in serum and plasma.
AB  - The "layer-by-layer" (LbL) technology has been widely investigated for the
      coating of flat substrates and capsules with polyelectrolytes. In this study, LbL
      polyelectrolyte coatings applied at the surface of digitally encoded
      microcarriers were evaluated for the quantitative, sensitive, and simultaneous
      detection of proteins in complex biological samples like serum, plasma, and
      blood. LbL coated microcarriers were therefore coupled to capture antibodies,
      which were used as capture agents for the detection of tumor necrosis factor (TNF
      alpha), P24, and follicle stimulating hormone (FSH). It was found that the LbL
      coatings did not disassemble upon incubating the microcarriers in serum and
      plasma. Also, nonspecific binding of target analytes to the LbL coating was not
      observed. We showed that the LbL coated microcarriers can reproducibly detect TNF
      alpha, P24, and FSH down to the picogram per milliliter level, not only in buffer
      but also in serum and plasma samples. Microcarrier-to-microcarrier intratube
      variations were less then 30%, and interassay variations less than 8% were
      observed. This paper also shows evidence that the LbL coated digitally encoded
      microcarriers are ideally suited for assaying proteins in "whole" blood in
      microfluidic chips, which are of high interest for "point-of-care" diagnostics.

PMID- 18052133
TI  - Gas-phase electronic spectra of two substituted benzene cations: phenylacetylene+
      and 4-fluorostyrene+.
AB  - The visible spectra of phenylacetylene+ and 4-fluorostyrene+ have been measured
      by laser photodissociation spectroscopy. The observed vibronic systems were
      assigned to the B2A'' <-- X2A'' and C2B1 <-- X2B1 electronic transition in the 4
      fluorostyrene+ and phenylacetylene+ cations, respectively. Two methods were
      employed and compared: a resonant multiphoton dissociation scheme of the bare
      cations and a resonant photodissociation technique applied to the chromophore+
      argon n=1,2 ionic complexes. The latter approach allowed the intrinsic profile to
      be resolved, revealing different intramolecular dynamical behavior. Their
      electronic relaxation has been rationalized in terms of an apparent energy gap
      law for the benzene derivative cations.

PMID- 18052132
TI  - Molecular interactions in lipophilic environments studied by electrochemistry at
      interfaces between immiscible electrolyte solutions.
AB  - The description and understanding of absorption and distribution of potential new
      drug compounds in the organism is of paramount importance for the successful
      development of new drugs. However, the currently used physical chemical
      parameters such as oil-water distribution coefficients and ionization constants
      frequently fall short when it comes to a detailed description of the highly
      heterogeneous environments of both lipophilic and hydrophilic characters through
      which the drug compound passes. In this work, a new procedure based on
      electrochemistry at the interface between immiscible electrolyte solutions for
      addressing drug compound-ligand interactions in lipophilic environments as well
      as nonspecific ligand effects on distribution behavior has been developed. An
      attractive feature of the method is that it can simultaneously provide data for
      oil-water partition coefficients and ionization constants. The new procedure is
      demonstrated using five drug compounds with different physical chemical
      parameters and cholesterol as the oil-phase ligand. The use of ligand shift ion
      partition diagrams in the data presentation allows a quick visualization and
      comparison of a series of related drug compounds.

PMID- 18052134
TI  - Ionized state of hydroperoxy radical-water hydrogen-bonded complex: (HO2-H2O)+.
AB  - Ab initio molecular orbital calculations have been employed to characterize the
      structure and bonding of the (HO2-H2O)+ radical cation system. Geometry
      optimization of this system was carried out using unrestricted density functional
      theory in conjunction with the BHHLYP functional and 6-311++G(2df,2p) as well as
      6-311++G(3df,3p) basis sets, the second-order Moller-Plesset perturbation (MP2)
      method with the 6-311++G(3df,3p) basis set, and the couple cluster (CCSD) method
      with the aug-cc-pVTZ basis set. The effect of spin multiplicity on the stability
      of the (HO2-H2O)+ system has been studied and also compared with that of oxygen.
      The calculated results suggest a proton-transferred hydrogen bond between HO2 and
      H2O in H3O3+ wherein a proton is partially transferred to H2O producing the
      O2...H3O+ structure. The basis set superposition error and zero-point energy
      corrected results indicate that the H3O3+ system is energetically more stable in
      the triplet state; however, the singlet state of H3O3+ is more stable with
      respect to its dissociation into H3O+ and singlet O2. Since the resulting proton
      transferred hydrogen-bonded complex (O2...H3O+) consists of weakly bound
      molecular oxygen, it might have important implications in various chemical
      processes and aquatic life systems.

PMID- 18052136
TI  - Molecular simulation of the hydration of ethene to ethanol using ab initio
      potentials and free energy curves.
AB  - Molecular dynamics simulations of aqueous solutions at infinite dilution of the
      reaction of water with ethene: H2O + CH2CH2 --> CH3CH2OH were performed using
      Lennard-Jones 12-6-1 potentials to describe the solute-solvent interactions, and
      TIP3P to describe the water-water interactions. The Morokuma decomposition scheme
      of ab initio interaction energies at the SCF level and the dispersion component
      at the MP2 level were used to reproduce the molecular parameters of the solute
      water interaction potentials. The results show that the functions that use the EX
      PL-DIS-ES interaction model to describe the solvation of the reactant, transition
      state, and product systems lead to good values of the reaction (Delta G) and
      acceptable values of the activation (Delta G#) free energy as compared with those
      from using AMBER-derived parameters, using the available theoretical and
      experimental data as referents.

PMID- 18052135
TI  - Theoretical studies on hydrogen bonding, NMR chemical shifts and electron density
      topography in alpha, beta and gamma-cyclodextrin conformers.
AB  - Hydrogen-bonded interactions in alpha-, beta-, and gamma-CD conformers are
      investigated from the molecular electron density topography and chemical shift in
      the nuclear magnetic resonance (NMR) spectra calculated by using the Gauge
      Invariant Atomic Orbital (GIAO) method within the framework of density functional
      theory. For the lowest-energy CD conformers in the gas phase, the O3-H...O2'
      hydrogen-bonding interactions are present. Calculated 1H NMR chemical shifts
      (delta H) correlate well with the hydrogen-bond distance as well as electron
      density at the bond critical point in the molecular electron density (MED)
      topography. The conformers of beta- and gamma-CD comprised of relatively strong
      secondary hydroxyl interactions are stabilized by solvation from polar solvents.

PMID- 18052137
TI  - Collisions of highly vibrationally excited pyrazine (E vib = 37,900 cm(-1)) with
      HOD: state-resolved probing of strong and weak collisions.
AB  - This work presents state-resolved measurements of weak and strong collisions
      between HOD and highly vibrationally excited pyrazine (Evib = 37,900 cm(-1)).
      Transient IR absorption line profiles of HOD(000) rotational states that are
      populated in single collisions with pyrazine (Evib) are fit using double-Gaussian
      functions to extract Doppler-broadened line widths and energy transfer rates for
      appearance and depletion populations. We recently reported the use of this new
      approach to determine collision rates for energy transfer (Havey, D. K.; Liu, Q.;
      Li, Z. M.; Elioff, M.; Fang, M.; Neudel, J.; Mullin, A. S. J. Phys. Chem. A 2007,
      111, 2458-2460). Here we present a full description of transient measurements of
      weak collisions, along with rate constants and the full energy transfer
      distribution function for the vibrational-to-rotation/translation (V-RT) pathway.
      The low- and high-J populations of scattered HOD(000) are characterized by a
      single rotational distribution with Trot = 430 +/- 50 K. The average
      translational energy of the scattered HOD(000) increases modestly with rotational
      energy suggesting an impulsive energy transfer mechanism. The energy gain
      distribution P(Delta E) for HOD(000) shows that approximately 99% of collisions
      have DeltaE values less than 3000 cm(-1). These data yield a lower limit to the
      collision rate that is approximately 70% larger than the calculated Lennard-Jones
      collision rate. These findings show that water is an efficient quencher due to a
      large collisional energy transfer cross section and not as a result of a large
      supercollision tail.

PMID- 18052138
TI  - Mechanistic study on the enantiodifferentiating anti-Markovnikov photoaddition of
      alcohols to 1,1-diphenyl-1-alkenes in near-critical and supercritical carbon
      dioxide.
AB  - Enantiodifferentiating anti-Markovnikov photoaddition of alcohol (methanol,
      ethanol, 2-propanol, and tert-butanol) to aromatic alkene (1,1-diphenylpropene
      and 1,1-diphenyl-1-butene), sensitized by optically active alkyl and saccharide
      naphthalene(di)carboxylates, was investigated in supercritical carbon dioxide at
      varying pressures to elucidate the effects of clustering on photosensitization
      and enantiodifferentiation behavior, in particular on the product's enantiomeric
      excess (ee). For all the alkene/alcohol/chiral sensitizer combinations examined,
      a sudden change in the product's ee was consistently observed near the critical
      density, which is attributable to the critical pressure dependence of clustering
      around the intervening exciplex intermediate.

PMID- 18052139
TI  - Crossed molecular beam study on the reaction of boron atoms, B(2Pj), with allene,
      H2CCCH2(X1A1).
AB  - The reaction of ground state boron atoms, 11B(2Pj), with allene, H2CCCH2(X1A1),
      was studied under single collision conditions at a collision energy of 21.5 kJ
      mol(-1) utilizing the crossed molecular beam technique; the experimental data
      were combined with electronic structure calculations on the 11BC3H4 potential
      energy surface. The chemical dynamics were found to be indirect and initiated by
      an addition of the boron atom to the pi-electron density of the allene molecule
      leading ultimately to a cyclic reaction intermediate. The latter underwent ring
      opening to yield an acyclic intermediate H2CCBCH2. As derived from the center-of
      mass functions, this structure was long-lived with respect to its rotational
      period and decomposed via an atomic hydrogen loss through a tight exit transition
      state to form the closed shell, C2v symmetric H-C is equivalent C-B=CH2 molecule.
      A brief comparison of the product isomers formed in the reaction of boron atoms
      with methylacetylene is also presented.

PMID- 18052140
TI  - Probing the dependence of long-range, four-atom interactions on intermolecular
      orientation. 1. Molecular hydrogen and iodine monochloride.
AB  - The dependence of the long-range interactions between molecular hydrogen and
      iodine monochloride on the geometry between the molecules is investigated. Laser
      induced fluorescence and action spectroscopy experiments have identified multiple
      conformers of the o,p-H2...I35,37Cl(X,v' '=0) van der Waals complexes. A
      conformer with the hydrogen molecule localized at the iodine end of the
      dihalogen, most likely with C2v symmetry, is significantly more stable than an
      asymmetric conformer with the hydrogen localized in the well oriented
      orthogonally to the I-Cl bond axis, D0' ' = 186.4(3) cm-1 versus 82.8(3) <or= D0'
      ' <or= 89.6(3) cm-1. Complexes containing the o-H2(j=1) species are more strongly
      bound than those with p-H2(j=0). The electronically excited o,p-H2...I35Cl(A,v')
      and o,p-H2...I35,37Cl(B,v') complexes are found to have preferred asymmetric
      structures with binding energies bracketed between 73.7-80.5 and 69.5-76.3 cm(-1)
      for o-H2... I35Cl(A,v'=23) and o-H2...I35Cl(B,v'=3), respectively. Calculations
      of the H2...I35Cl(B,v'=3) intermolecular vibrational energies and probability
      amplitudes undertaken using a scaled He + ICl(B,v'=3) potential enable us to make
      tentative assignments of the excited-state levels experimentally accessed.

PMID- 18052141
TI  - Chromium-doped germanium clusters CrGen (n = 1-5): geometry, electronic
      structure, and topology of chemical bonding.
AB  - The structure and properties of small neutral and cationic CrGen(0,+) clusters,
      with n from 1 to 5, were investigated using quantum chemical calculations at the
      CASSCF/CASPT2 and DFT/B3LYP levels. Smaller clusters prefer planar geometries,
      whereas the lowest-lying electronic states of the neutral CrGe4, CrGe5, and
      cationic CrGe5+ forms exhibit nonplanar geometries. Most of the clusters
      considered prefer structures with high-spin ground state and large magnetic
      moments. Relative to the values obtained for the pure Gen clusters, fragmentation
      energies of doped CrGen clusters are smaller when n is 3 and 4 and larger when n
      = 5. The averaged binding energy tends to increase with the increasing number of
      Ge atoms. For n = 5, the binding energies for Ge5, CrGe5, and CrGe5+ are similar
      to each other, amounting to approximately 2.5 eV. The Cr atom acts as a general
      electron donor in neutral CrGen clusters. Electron localization function (ELF)
      analyses suggest that the chemical bonding in chromium-doped germanium clusters
      differs from that of their pure or Li-doped counterparts and allow the origin of
      the inherent high-spin ground state to be understood. The differential DeltaELF
      picture, obtained in separating both alpha and beta electron components, is
      consistent with that derived from spin density calculations. For CrGen, n = 2 and
      3, a small amount of d-pi back-donation is anticipated within the framework of
      the proposed bonding model.

PMID- 18052142
TI  - Human microsomal prostaglandin E synthase-1 (mPGES-1) binding with inhibitors and
      the quantitative structure-activity correlation.
AB  - The detailed structures of microsomal prostaglandin E synthase-1 (mPGES-1)
      binding with inhibitors have been studied, for the first time, by using a newly
      developed computational three-dimensional (3D) structural model of mPGES-1 along
      with a 3D-quantitative structure--activity relationship (3D-QSAR) analysis. The
      obtained satisfactory binding structures and 3D-QSAR models strongly suggest that
      the 3D structural model of mPGES-1 is reasonable for study of mPGES-1 binding
      with inhibitors and for future design of novel mPGES-1 inhibitors.

PMID- 18052144
TI  - Decoupling of the nernst-planck and poisson equations. Application to a membrane
      system at overlimiting currents.
AB  - This paper deals with one-dimensional stationary Nernst-Planck and Poisson (NPP)
      equations describing ion electrodiffusion in multicomponent solution/electrode or
      ion-conductive membrane systems. A general method for resolving ordinary and
      singularly perturbed problems with these equations is developed. This method is
      based on the decoupling of NPP equations that results in deduction of an equation
      containing only the terms with different powers of the electrical field and its
      derivatives. Then, the solution of this equation, analytical in several cases or
      numerical, is substituted into the Nernst-Planck equations for calculating the
      concentration profile for each ion present in the system. Different ionic species
      are grouped in valency classes that allows one to reduce the dimension of the
      original set of equations and leads to a relatively easy treatment of multi-ion
      systems. When applying the method developed, the main attention is paid to ion
      transfer at limiting and overlimiting currents, where a significant deviation
      from local electroneutrality occurs. The boundary conditions and different
      approximations are examined: the local electroneutrality (LEN) assumption and the
      original assumption of quasi-uniform distribution of the space charge density
      (QCD). The relations between the ion fluxes at limiting and overlimiting currents
      are discussed. In particular, attention is paid to the "exaltation" of counterion
      transfer toward an ion-exchange membrane by co-ion flux leaking through the
      membrane or generated at the membrane/solution interface. The structure of the
      multi-ion concentration field in a depleted diffusion boundary layer (DBL) near
      an ion-exchange membrane at overlimiting currents is analyzed. The presence of
      salt ions and hydrogen and hydroxyl ions generated in the course of the water
      "splitting" reaction is considered. The thickness of the DBL and its different
      zones, as functions of applied current density, are found by fitting experimental
      current-voltage curves.

PMID- 18052146
TI  - Heterogeneous nucleation of nitric acid trihydrate on clay minerals: relevance to
      type ia polar stratospheric clouds.
AB  - Although critical to atmospheric modeling of stratospheric ozone depletion,
      selective heterogeneous nuclei that promote the formation of Type Ia polar
      stratospheric clouds (PSCs) are largely unknown. While mineral particles are
      known to be good ice nuclei, it is currently not clear whether they are also good
      nuclei for PSCs. In the present study, a high-vacuum chamber equipped with
      transmission Fourier transform infrared spectroscopy and a quadrupole mass
      spectrometer was used to study heterogeneous nucleation of nitric acid trihydrate
      (NAT) on two clay minerals-Na-montmorillonite and kaolinite-as analogs of
      atmospheric terrestrial and extraterrestrial minerals. The minerals are first
      coated with a 3:1 supercooled H2O/HNO3 solution prior to the observed nucleation
      of crystalline NAT. At 220 K, NAT formation was observed at low SNAT values of 12
      and 7 on kaolinite and montmorillonite clays, respectively. These are the lowest
      SNAT values reported in the literature on any substrate. However, NAT nucleation
      exhibited significant temperature dependence. At lower temperatures,
      representative of typical polar stratospheric conditions, much higher
      supersaturations were required before nucleation was observed. Our results
      suggest that NAT nucleation on mineral particles, not previously treated with
      sulfuric acid, may not be an important nucleation platform for Type Ia PSCs under
      normal polar stratospheric conditions.

PMID- 18052145
TI  - Crystal polymorphism of protein GB1 examined by solid-state NMR spectroscopy and
      X-ray diffraction.
AB  - The study of micro- or nanocrystalline proteins by magic-angle spinning (MAS)
      solid-state NMR (SSNMR) gives atomic-resolution insight into structure in cases
      when single crystals cannot be obtained for diffraction studies. Subtle
      differences in the local chemical environment around the protein, including the
      characteristics of the cosolvent and the buffer, determine whether a protein will
      form single crystals. The impact of these small changes in formulation is also
      evident in the SSNMR spectra; however, the changes lead only to correspondingly
      subtle changes in the spectra. Here, we demonstrate that several formulations of
      GB1 microcrystals yield very high quality SSNMR spectra, although only a subset
      of conditions enable growth of single crystals. We have characterized these
      polymorphs by X-ray powder diffraction and assigned the SSNMR spectra.
      Assignments of the 13C and 15N SSNMR chemical shifts confirm that the backbone
      structure is conserved, indicative of a common protein fold, but side chain
      chemical shifts are changed on the surface of the protein, in a manner dependent
      upon crystal packing and electrostatic interactions with salt in the mother
      liquor. Our results demonstrate the ability of SSNMR to reveal minor structural
      differences among crystal polymorphs. This ability has potential practical
      utility for studying the formulation chemistry of industrial and therapeutic
      proteins, as well as for deriving fundamental insights into the phenomenon of
      single-crystal growth.

PMID- 18052147
TI  - Difference in the dynamic properties of chiral and racemic crystals of serine
      studied by Raman spectroscopy at 3-295 K.
AB  - Single-crystal polarized Raman spectra (60-4000 cm(-1) at 3 < or = T < or = 295
      K) were measured for chiral L- and racemic DL-serine, alpha-amino-beta
      hydroxypropionic acid, (NH3)+CH(CH2OH)(COO)-. The Raman spectra of dl-serine do
      not show any striking changes with temperature or on storage. In contrast to
      that, the dynamical properties of L-serine change at about 140 K. These changes
      can be interpreted as the reorientation of the side chain -CH2OH fragments of the
      zwitterions with respect to the backbone C-C bonds, resulting in the positional
      disorder of the O-H...O intermolecular H-bonds. The redistribution in the
      intensities of the Raman spectra of the crystals of L-serine stored for a long
      time (about a year) indicates the changes in the orientation of the molecular
      fragments in the direction normal to the axes of the head-to-tail chains. The
      difference in the thermodynamic functions of L- and DL-serine reported previously
      [Drebushchak, V. A.; Kovalevskaya, Yu. A.; Paukov, I. E.; Boldyreva, E. V. J.
      Therm. Anal. Calorim. 2007, 89 (2), 649-654] is explained by the difference in
      the spectra of external vibrations of the crystals.

PMID- 18052148
TI  - Structure and properties of low molecular weight amphiphilic peptide
      hydrogelators.
AB  - The search for low molecular weight hydrogelators (LMWH) with varying structural
      motif is getting intense because of its potential application in the field of
      biomedicines as well as the diversified area of nano-biotechnology. In this
      paper, we have developed hydrogels of simple cationic dipeptide amphiphiles that
      have a wide range of minimum gelation concentration (MGC), 12-0.25% (w/v) in
      plain water. The self-aggregation behavior of these thermoreversible
      hydrogelators has been investigated through different spectroscopic and
      microscopic techniques. A balanced participation of hydrophilicity and
      hydrophobicity is the major driving force for gelation, which could be modulated
      by a minute change in the architecture of the amphiphile head. The prospective
      use of this material in controlled release suggests that this system could also
      be applied as the drug delivery vehicle. Moreover, the presence of a
      biodegradable amide linkage susceptible to base or enzyme-catalyzed hydrolysis
      increases its probable applications as biomaterials.

PMID- 18052149
TI  - Heterogeneous and anomalous diffusion inside lipid tubules.
AB  - Self-assembled lipid tubules with crystalline bilayer walls are promising
      candidates for controlled drug delivery vehicles on the basis of their ability to
      release preloaded biological molecules in a sustained manner. While a previous
      study has shown that the release rate of protein molecules from lipid tubules
      depends on the associated molecular mass, suggesting that the pertinent diffusion
      follows the well-known Stokes-Einstein relationship, only a few attempts have
      been made toward investigating the details of molecular diffusion in the tubule
      interior. Herein, we have characterized the diffusion rates of several molecules
      encapsulated in lipid tubules formed by 1,2-bis(10,12-tricosadiynoyl)-sn-glycero
      3-phosphocholine (DC8,9PC) using the techniques of fluorescence recovery after
      photobleaching (FRAP) and fluorescence correlation spectroscopy (FCS). Our
      results show that the mobility of these molecules depends not only on their
      positions in the DC8,9PC tubules but also on their respective concentrations.
      While the former indicates that the interior of the DC8,9PC tubules is
      heterogeneous in terms of diffusion, the latter further highlights the
      possibility of engineering specific conditions for achieving sustained release of
      a "drug molecule" over a targeted period of time. In addition, our FCS results
      indicate that the molecular diffusions inside the crystalline bilayer walls of
      the DC8,9PC tubules strongly deviate from the normal, stochastic processes, with
      features characterizing not only anomalous subdiffusions but also motions that
      are superdiffusive in nature.

PMID- 18052150
TI  - Microstructure control of Zn/ZnO core/shell nanoparticles and their temperature
      dependent blue emissions.
AB  - The microstructure of the Zn/ZnO core/shell nanoparticles synthesized by laser
      ablation in liquid medium can be facilely controlled. With the surfactant
      concentration increased over the critical micelle concentration, the nanoparticle
      transformed from pure ZnO to a Zn/ZnO core/shell structure. Further, with a
      decrease of the applied laser power, the ZnO shell thickness was monotonously
      reduced till 2.5 nm and the ultrafine ZnO nanocrystals embedded in the nanoshells
      were also reduced till 1.5 nm, which induced the increase of the disorder degree
      of the nanoshell lattice. The controlling mechanism was discussed according to
      the competition of capping protection and the oxidation reaction of laser-induced
      plasma. Blue photoluminescence from the ZnO nanoshells was observed. The emission
      band exhibited abnormal red-blue shift and narrowing with increasing temperature.
      Such temperature-dependent behaviors can be well described by a localization
      model involving an interstitial zinc defect center. These results indicate that
      this method provides a convenient and universal way to obtain various metal/oxide
      core/shell nanoparticles with controllable microstructure, and it will be
      beneficial to an understanding of the physical origins of the blue emission in
      nanostructured ZnO as well as to extending its optical and electronic
      applications.

PMID- 18052151
TI  - Spectroscopic studies of dehydrogenation of ammonia borane in carbon cryogel.
AB  - Ammonia borane (AB) is of great interest for storing hydrogen, an important issue
      in the growing field of hydrogen technology. The reaction pathways leading to the
      thermal decomposition of solid-state AB incorporated in carbon cryogels (CC) have
      been studied by spectroscopic methods. The time-dependent thermal decomposition
      was followed by in situ 11B nuclear magnetic resonance (NMR) and showed a
      significant increase in hydrogen release kinetics for AB in CC compared to neat
      AB. Both 11B NMR and Fourier transform infrared spectroscopy show a new reaction
      product, formed in the thermal decomposition of AB in CC scaffold (CC-AB) that is
      assigned to reactions with surface oxygen groups. The results indicate that
      incorporation of AB in CC enhances kinetics because of the reactions with
      residual surface-bound oxygen functional groups. The formation of new products
      with surface -O-B bonds is consistent with the greater reaction exothermicity
      observed when hydrogen is released from CC-AB materials. Scanning electron
      microscopy shows different morphology of AB in CC-AB nanocomposite as compared to
      neat AB.

PMID- 18052152
TI  - Sub-nanometer control of the interlayer spacing in thin films of intercalated
      rodlike conjugated molecules.
AB  - Organic molecular beam co-deposition of rodlike conjugated molecules with an
      alkylated analogue resulted in thin film structures with layers of alternating
      semiconducting (conjugated molecular parts) and insulating (alkyl parts)
      character. By varying the alkylated molecule ratio, we could adjust the distance
      between conjugated layers with sub-nanometer precision, exploiting the mechanical
      flexibility of the alkyl chains. Furthermore, due to mutual molecular
      intercalation, mixed layers containing two conjugated moieties with vastly
      different electronic properties could be fabricated.

PMID- 18052153
TI  - Aggregation of ionic surfactants to block copolymer assemblies: a simple
      fluorescence spectral study.
AB  - A simple and elegant method based on steady-state fluorescence spectral
      measurement is demonstrated to study the interaction mechanism of copolymers and
      ionic surfactants with a suitable selection of fluorescent probe and also its
      general applicability in studying other systems. Three different concentration
      regions have been indicated from the changes in full width at half-maximum of the
      emission spectra and fluorescence intensity of coumarin 153 with the molar ratio
      of ionic surfactant to triblock copolymer (n). At low n values, copolymer
      surfactant complexes are basically copolymer-rich micelles with few surfactant
      molecules, and at very high n values, copolymer-rich micelles are destroyed and
      surfactant-rich micelles with free copolymer monomers are formed. It has been
      observed that, in the intermediate surfactant concentration region, the
      transformation of a dominantly copolymer-rich complex to a mainly surfactant-rich
      complex can be either gradual incorporation of surfactants into the copolymer
      rich micelles with freeing of copolymer units until surfactant-rich micelles are
      formed (type I) or simultaneous buildup of surfactant-rich micelles together with
      the destruction of copolymer-rich micelles (type II). The interaction mechanism
      for nonionic copolymers (P123 and F127) with ionic surfactants (SDS and CTAC) is
      mainly type II, but at higher copolymer concentrations interaction via the type I
      mechanism also operates. However, it is dominantly the type I mechanism that
      operates for common nonionic (TX100) and ionic surfactants.

PMID- 18052154
TI  - Adiabatically bound valence anions of guanine.
AB  - It is believed that guanine, a basic component of DNA and RNA, has the smallest
      affinity to an excess electron among all nucleic acid bases. Our experimental and
      computational findings indicate, however, that many so far neglected tautomers of
      guanine support adiabatically bound anionic states in the gas phase. The computed
      values of electron vertical detachment energy for the most stable anionic
      tautomers are within a broad range of the dominant feature of the photoelectron
      spectrum. We suggest that guanine might be the strongest excess electron acceptor
      among nucleic acid bases. Thus it might be critical to radiobiological damage of
      DNA and it might contribute to those chemical transformations of DNA that proceed
      through bound anionic states.

PMID- 18052155
TI  - Accurate steady-state and zero-time fluorescence spectra of large molecules in
      solution by a first-principle computational method.
AB  - We report the first-principle calculation and analysis of the vibrationally
      resolved steady-state absorption and fluorescence spectra, and of the zero-time
      fluorescence spectrum of a sizable molecule, coumarin C153, in two different
      solvents. Our approach, bringing together the most recent developments in the
      fields of time-dependent density functional theory and of polarizable continuum
      solvent models, with an efficient method for the computation of vibrational
      contributions to transition intensities, allows a remarkable agreement with
      experiments, both concerning the line shapes and the solvatochromic and Stokes
      shifts. The method is also able to nicely describe the solvent relaxation effect
      on the fluorescence spectra, perfectly reproducing the energy shift between zero
      time and steady-state fluorescence.

PMID- 18052156
TI  - Multiple charge-transfer emissions from different metal-ligand pairs in ruthenium
      diimines.
AB  - Ruthenium diimines are unique in their emissivity. Optical excitation with light
      of less than 500 nm leads to a strong emission in the 600-700 nm range. All
      emissive ruthenium complexes appear to undergo intersystem crossing from the
      absorptive singlet metal-to-ligand charge-transfer (MLCT) state to an emissive
      triplet MLCT state localized on the lowest-energy metal-ligand pair. In contrast
      to this currently accepted model, in which a single emissive state is populated
      and then equilibrates among other states based on a particular set of conditions,
      the excitation-wavelength dependence of the [(bpy)2RudppH]3+ emission suggests
      two emissive pathways. One populates an emissive MLCT state localized on a bpy-Ru
      pair, and the other populates a lower-energy MLCT state localized on the dpp-Ru
      pair.

PMID- 18052157
TI  - Xenon difluoride induced aryl iodide reductive elimination: a simple access to
      difluoropalladium(II) complexes.
AB  - Palladium(II) aryliodo complexes bearing chelating diphosphine ligands react with
      XeF2, giving iodoarene and rare palladium(II) difluoro complexes. The reaction is
      general with regard to the aryl group, with even C6F5-I undergoing facile
      reductive elimination from a Pd center.

PMID- 18052158
TI  - Carbon monoxide coordination and reversible photodissociation in copper(I)
      pyridylalkylamine compounds.
AB  - Systematic studies of CO coordination and photodissociation have been carried out
      for a series of copper(I) carbonyl compounds possessing tripodal tetradentate
      ligands, [CuI(L)(CO)]B(C6F5)4 (L = Me2N-TMPA (1Me2N), MeO-TMPA (1MeO), H-TMPA
      (1H), PMEA (2pmea), PMAP (2pmap), BQPA (3bqpa). Detailed structural,
      electrochemical, and infrared characterization has been accomplished. In
      addition, various experimental techniques were utilized to determine equilibrium
      binding constants (KCO), association (kCO), and dissociation (k-CO) rate
      constants, as well as the thermodynamic (DeltaH degrees , DeltaS degrees ) and
      activation parameters (DeltaH, DeltaS) that regulate these processes. With
      increased ligand-electron-donating ability, greater pi back-bonding results in
      stronger Cu-CO bonds, leading to KCO values on the order 1Me2N-CO > 1MeO-CO > 1H
      CO. With systematic synthetic expansion of the five-membered chelate rings like
      1R to six-membered chelate rings like 2R, the stability of the CO adduct
      decreases, 1H-CO > 2pmea-CO > 2pmap-CO. The CO-binding properties of 3bqpa did
      not follow trends observed for the other compounds, presumably because of its
      bulkier ligand framework. Through solid- and solution-state analyses, we
      concluded that the photolabile carbonyl species in solution possess a tridentate
      coordination mode, forming strictly five-membered chelate rings to the copper ion
      with one dangling arm of the tripodal ligand. Carbon monoxide reversibly
      photodissociated from complexes 1Me2N-CO, 1MeO-CO, 1H-CO, and 3bqpa-CO in
      coordinating (CH3CN) and weakly coordinating (THF) solvent but not from 2pmea-CO
      and 2pmap-CO. Comparisons to O2-binding data available for these copper complexes
      as well as to small molecule (O2, CO, NO) reactions with hemes and copper
      proteins are discussed.

PMID- 18052160
TI  - Methylrhenium trioxide revisited: mechanisms for nonredox oxygen insertion in an
      M-CH3 bond.
AB  - Methylrhenium trioxide (MTO) has the rare ability to stoichiometrically generate
      methanol at room temperature with an external oxidant (H2O2) under basic
      conditions. In order to use this transformation as a model for nonredox oxidative
      C-O coupling, the mechanisms have been elucidated using density functional theory
      (DFT). Our studies show several possible reaction pathways to form methanol, with
      the lowest net barrier (DeltaH++) being 23.3 kcal mol-1. The rate-determining
      step is a direct "Baeyer-Villiger" type concerted oxygen insertion into MTO,
      forming methoxyrhenium trioxide. The key to the low-energy transition state is
      the donation of electron density, first, from HOO(-) to the -CH3 group (making 
      CH3 more nucleophilic and HOO- more electrophilic) and, second, from the Re-C
      bond to both the forming Re-O and breaking O-O bonds, simultaneously (thus
      forming the Re-O bond as the Re-C bond is broken). In turn, the ability of MTO to
      undergo these transfers can be traced to the electrophilic nature of the metal
      center and to the absence of accessible d-orbitals. If accessible d-orbitals are
      present, they would most likely donate the required electron density instead of
      the M-CH3 moiety, and this bond would thus not be broken. It is possible that
      other metal centers with similar qualities, such as PtIV or IrV, could be
      competent for the same type of chemistry.

PMID- 18052161
TI  - 13C-detection in RNA bases: revealing structure-chemical shift relationships.
AB  - The chemical shifts of the unprotonated carbons in the proton-deficient
      nucleobases of RNA are rarely reported, despite the valuable information that
      they contain about base-pairing and base-stacking. We have developed 13C-detected
      2D-experiments to identify the unprotonated 13C in the RNA bases and have
      assigned all the base nuclei of uniformly 13C,15N-labeled HIV-2 TAR-RNA. The 13C
      chemical shift distributions revealed perturbations correlated with the base
      pairing and base-stacking properties of all four base-types. From this work, we
      conclude that the information contained in the chemical shift perturbations
      within the base rings can provide valuable restraint information for solving RNA
      structures, especially in conformational averaged regions, where NOE-based
      information is not available.

PMID- 18052162
TI  - Supramolecular carbon nanotube-fullerene donor-acceptor hybrids for photoinduced
      electron transfer.
AB  - Photoinduced electron transfer in a self-assembled single-wall carbon nanotube
      (SWNT)-fullerene(C60) hybrid with SWNT acting as an electron donor and fullerene
      as an electron acceptor has been successfully demonstrated. Toward this, first,
      SWNTs were noncovalently functionalized using alkyl ammonium functionalized
      pyrene (Pyr-NH3+) to form SWNT/Pyr-NH3+ hybrids. The alkyl ammonium entity of
      SWNT/Pyr-NH3+ hybrids was further utilized to complex with benzo-18-crown-6
      functionalized fullerene, crown-C60, via ammonium-crown ether interactions to
      yield SWNT/Pyr-NH3+/crown-C60 nanohybrids. The nanohybrids were isolated and
      characterized by TEM, UV-visible-near IR, and electrochemical methods. Free
      energy calculations suggested possibility of electron transfer from the carbon
      nanotube to the singlet excited fullerene in the SWNT/Pyr-NH3+/crown-C60
      nanohybrids. Accordingly, steady-state and time-resolved fluorescence studies
      revealed efficient quenching of the singlet excited-state of C60 in the
      nanohybrids. Further studies involving nanosecond transient absorption studies
      confirmed electron transfer to be the quenching mechanism, in which the electron
      transfer product, fullerene anion radical, was possible to spectrally
      characterize. The rates of charge separation, kCS, and charge recombination, kCR,
      were found to be 3.46 x 10(9) and 1.04 x 10(7) s-1, respectively. The calculated
      lifetime of the radical ion-pair was found to be over 100 ns, suggesting charge
      stabilization in the novel supramolecular nanohybrids. The present nanohybrids
      were further utilized to reduce hexyl-viologen dication (HV2+) and a sacrificial
      electron donor, 1-benzyl-1,4-dihydronicotinamide, in an electron-pooling
      experiment, offering additional proof for the occurrence of photoinduced charge
      separation and potential utilization of these materials in light-energy
      harvesting applications.

PMID- 18052163
TI  - Biomimetic aminoacylation of ribonucleotides and RNA with aminoacyl phosphate
      esters and lanthanum salts.
AB  - Aminoacylation of tRNA in cells involves activation of the amino acid as an
      aminoacyl adenylate, a mixed anhydride with AMP, which reacts with tRNA. We have
      now established that aminoacyl phosphate esters in the presence of lanthanide
      ions in water will acylate hydroxyls at the 3'-terminus of RNA or a simple
      nucleotide. By extension, this will permit synthetically aminoacylated tRNA to be
      produced in a single-step biomimetic process. The reactions of Boc-4
      fluorophenylalanyl ethyl phosphate were followed by HPLC separation, MS, and 19F
      NMR analysis. In stoichiometric combination with lanthanum salts in aqueous
      buffer, Boc-4-fluorophenylalanyl ethyl phosphate rapidly produces 2'- and 3'
      monoesters of cytidine and cytidine monophosphate. Reaction of the reagent with
      RNA in the presence of lanthanum and magnesium salts introduces a specifically
      detectable signal into the RNA, which is evidence of formation of the aminoacyl
      ester. When the same RNA is initially oxidized with periodate to convert the 3'
      terminal vicinal diol to the cleaved dialdehyde, reaction with the aminoacyl
      phosphate no longer occurs as evidenced by the lack of a signal in the 19F NMR
      spectrum. The results are consistent with a requisite chelation mechanism in
      which lanthanum serves as a template for both the aminoacyl phosphate and the 3'
      terminal diol of RNA and nucleotides. The coordinated diol will then react
      through specific base-catalyzed intramolecular addition of the alkoxide
      nucleophile to the acyl group of the aminoacyl phosphate. Assessment of the
      method with a single tRNA was also achieved using the fluorescent reagent N
      dansyl-glycyl ethyl phosphate. Lanthanide-promoted aminoacylation at the 3'
      terminus of tRNAPhe is detected by the introduction of fluorescence (detected
      directly and by antibody-enhanced emission). This does not occur if the 3'
      terminus is converted to the dialdehyde by reaction with periodate.

PMID- 18052164
TI  - The reversal by sulfate of the denaturant activity of guanidinium.
AB  - Guanidinium (Gdm+) chloride is a powerful protein denaturant, whereas the sulfate
      dianion (SO42-) is a strong stabilizer of folded protein states; Gdm2SO4 is
      effectively neutral in its effects on protein stability. While the "neutralizing"
      effects of protein-stabilizing solutes on the activity of denaturants can be
      broadly interpreted in terms of additive effects of the solutes, recent
      experimental and simulation studies support a role for hetero-ion interactions in
      the effect of sulfate on Gdm+ denaturation [Mason, P. E.; et al. J. Phys. Chem. B
      2005, 109, 24185-24196]. Here we describe an experimental strategy for testing
      this mechanism that involves spectroscopic analysis of the separate effects of
      alkali metal sulfates (Na2SO4, Rb2SO4), GdmCl, and Gdm2SO4 on the folded
      populations of several peptides chosen to dissect specific noncovalent
      contributions to the conformational stability of proteins [alanine-based helical
      peptides stabilized by hydrogen bonds, tryptophan zipper (trpzip) peptides
      stabilized largely by cross-strand indole-indole interactions]. While the trpzip
      peptides are highly sensitive to GdmCl denaturation, they are unaffected by NaCl,
      Na2SO4, or Gdm2SO4, indicating that the reversal of the denaturant activity of
      Gdm+ by sulfate in this case is not due to competing stabilizing (sulfate) and
      destabilizing (Gdm+) interactions. Gdm2SO4 was found to retain considerable
      denaturant activity against alanine-based alpha-helical peptides. The differences
      in the effects of Gdm2SO4 on the two peptide types can be understood in terms of
      the different mechanisms of Gdm+ denaturation of trpzip peptides and helical
      peptides, respectively, and the specific nature of Gdm+ and SO42- ionic
      "clustering" that differentially affects the ability of Gdm+ to make the
      molecular interactions with the peptides that underlie its denaturant activity.

PMID- 18052165
TI  - Scanning Kelvin probe imaging of the potential profiles in fixed and dynamic
      planar LECs.
AB  - We measure the potential profiles of both dynamic and fixed junction planar light
      emitting electrochemical cells (LECs) using Scanning Kelvin Probe Microscopy
      (SKPM) and compare the results against models of LEC operation. We find that, in
      conventional dynamic junction LECs formed using lithium trifluoromethanesulfonate
      (LiTf), poly(ethylene oxide) (PEO), and the soluble alkoxy-PPV derivative poly[2
      methoxy-5-(3',7'-dimethyl-octyloxy)-p-phenylenevinylene (MDMO-PPV), the majority
      (>90%) of the potential is dropped near the cathode with little potential drop
      across either the film or the anode/polymer interface. In contrast, when
      examining fixed junction LECs where the LiTf is replaced with [2
      (methacryloyloxy)ethyl] trimethylammonium 2-(methacryloyloxy)ethane-sulfonate
      (METMA/MES), the potential is dropped at both contacts during the initial poling.
      The potential profile evolves over a period of approximately 60 min under bias to
      achieve a final profile similar to that obtained in the LiTf systems. In addition
      to elucidating the differences between conventional dynamic LECs and fixed LECs
      incorporating cross-linkable ion pair monomers, the results on both systems
      provide direct evidence for a primarily "p-type" LEC consistent with the emitting
      junction near the cathode and relatively small electric fields across the bulk of
      the device for these two material systems.

PMID- 18052166
TI  - The beta effect of silicon in phenyl cations.
AB  - Irradiation of chloroanisoles, phenols, and N,N-dimethylanilines bearing a
      trimethylsilyl (TMS) group in the ortho position with respect to the chlorine
      atom caused photoheterolysis of the Ar-Cl bond and formation of the corresponding
      ortho-trimethylsilylphenyl cations in the triplet state. The beta effect of
      silicon on these intermediates has been studied by comparing the resulting
      chemistry in alcoholic solvents with that of the silicon-free analogues and by
      computational analysis (at the UB3LYP/6-311+G(2d,p) level in MeOH). TMS groups
      little affect the photophysics and the photocleavage of the starting phenyl
      chlorides, while stabilizing the phenyl cations, both in the triplet (ca. 4
      kcal/mol per group) and, dramatically, in the singlet state (9 kcal/mol). As a
      result, although triplet phenyl cations are the first formed species, intersystem
      crossing to the more stable singlets is favored with chloroanisoles and phenols.
      Indeed, with these compounds, solvent addition to give aryl ethers (from the
      singlet) competed efficiently with reduction or arylation (from the triplet). In
      the case of the silylated 4-chloro-N,N-dimethylaniline, the triplet cation
      remained in the ground state and trapping by pi nucleophiles remained efficient,
      though slowed by the steric bulk of the TMS group. In alcohols, the silyl group
      was eliminated via a photoinduced protiodesilylation during the irradiation.
      Thus, the silyl group could be considered as a directing, photoremovable group
      that allowed shifting to the singlet phenyl cation chemistry and was smoothly
      eliminated in the same one-pot procedure.

PMID- 18052167
TI  - Two [Fe(IV)=O Trp*] intermediates in M. tuberculosis catalase-peroxidase
      discriminated by multifrequency (9-285 GHz) EPR spectroscopy: reactivity toward
      isoniazid.
AB  - We have characterized the intermediates formed in the peroxidase cycle of the
      multifunctional heme-containing enzyme KatG of M. tuberculosis. Selected Trp
      variants from the heme proximal (W321F) and distal (W107F and W91F) sides were
      analyzed together with the wild-type enzyme with regard to the reaction with
      peroxyacetic acid and hydrogen peroxide (in the catalase-inactive W107F). The 9
      GHz EPR spectrum of the enzyme upon reaction with peroxyacetic acid showed the
      contribution of three protein-based radical species, two Trp* and a Tyr*, which
      could be discerned using a combined approach of multifrequency Electron
      Paramagnetic Resonance (EPR) spectroscopy with selective deuterium labeling of
      tryptophan and tyrosine residues and site-directed mutagenesis. Trp321, a residue
      in H-bonding interactions with the iron through Asp381 and the heme axial ligand
      His270, was identified as one of the radical sites. The 9 GHz EPR signal of the
      Trp321 radical species was consistent with an exchange-coupled species similar to
      the oxoferryl-Trp radical intermediate in cytochrome c peroxidase. On the basis
      of the possibility of distinguishing among the different radical intermediates of
      the peroxidase cycle in M. tuberculosis KatG (MtKatG), we used EPR spectroscopy
      to monitor the reactivity of the enzyme and its W321F variant with isoniazid, the
      front-line drug used in the treatment of tuberculosis. The EPR experiments on the
      W321F variant preincubated with isoniazid allowed us to detect the short-lived
      [Fe(IV)=O Por*+] intermediate. Our results showed that neither the [Fe(IV)=O
      Por*+] nor the [Fe(IV)=O Trp321*+] intermediates were the reactive species with
      isoniazid. Accordingly, the subsequent intermediate (most probably the other
      Trp*) is proposed to be the oxidizing species. Our findings demonstrate that the
      protein-based radicals formed as alternative intermediates to the [Fe(IV)=O
      Por*+] can play the role of cofactors for substrate oxidation in the peroxidase
      cyle of KatGs.

PMID- 18052168
TI  - Thermodynamics and kinetics of aggregation for the GNNQQNY peptide.
AB  - The energy landscape of the monomer and dimer are explored for the amyloidogenic
      heptapeptide GNNQQNY from the N-terminal prion-determining domain of the yeast
      protein Sup35. The peptide is modeled by a united-atom potential and an implicit
      solvent representation. Replica exchange molecular dynamics is used to explore
      the conformational space, and discrete path sampling is employed to investigate
      the pathways that interconvert the most populated minima on the free energy
      surfaces. For the monomer, we find a rapid fluctuation between four different
      conformations, where a geometry intermediate between compact and extended
      structures is the most thermodynamically favorable. The GNNQQNY dimer forms three
      stable sheet structures, namely in-register parallel, off-register parallel, and
      antiparallel. The antiparallel dimer is stabilized by strong electrostatic
      interactions resulting from interpeptide hydrogen bonds, which restrict its
      conformational flexibility. The in-register parallel dimer, which is close to the
      amyloid beta-sheet structure, has fewer interpeptide hydrogen bonds, making
      hydrophobic interactions more important and increasing the conformational entropy
      compared to the antiparallel sheet. The estimated two-state rate constants
      indicate that the formation of dimers from monomers is fast and that the dimers
      are kinetically stable against dissociation at room temperature. Interconversions
      between the different dimers are feasible processes and are more likely than
      dissociation.

PMID- 18052169
TI  - Porous crystal derived from a tricarboxylate linker with two distinct binding
      motifs.
AB  - The use of a reduced symmetry organic linker for the preparation of porous
      coordination polymers is demonstrated. The solvothermal reaction of the
      unsymmetrically substituted biaryl compound biphenyl-3,4',5-tricarboxylic acid
      with Cu(II) ions produces a [3,4,6]-connected coordination polymer exhibiting
      very high porosity and surface area (SLangmuir = 3100 m2/g). A striking feature
      of the structure is its incorporation, in a single material, of both the
      ubiquitous dinuclear Cu(II) paddlewheel motif and the rarely observed trinuclear
      Cu(II) cluster. Saturation H2 uptake, measured at 77 K, shows an excess
      gravimetric uptake of 5.7 wt % at 45 bar with a steep rise at low pressures.

PMID- 18052171
TI  - Spin accommodation and reactivity of aluminum based clusters with O2.
AB  - It is shown that spin accommodation plays a determining role in the reactivity of
      aluminum based anion clusters with oxygen. Experimental reactivity studies on
      aluminum and aluminum-hydrogen clusters show variable reactivity in even electron
      systems and rapid etching in odd electron systems. The reactivity of even
      electron clusters is governed by a spin transfer to the singlet cluster through
      filling of the spin down antibonding orbitals on triplet oxygen. Theoretical
      investigations show that when the spin transfer cannot occur, the species is
      unreactive. When spin accommodation is possible, more subtle effects appear, such
      as the required spin excitation energy, which raises the total energy of the
      system, and the filling of the antibonding levels of the O2 molecule, which is
      stabilized by becoming an aluminum oxygen pi bond. This explanation is consistent
      with observed behavior in oxygen etching reactions with a variety of clusters
      including AlnHm-, Aln-, AlnIm-, and AlnC-. The proposed reaction mechanism lends
      a physical interpretation as to why the HOMO-LUMO gap successfully predicts
      oxygen etching behavior of the considered systems.

PMID- 18052170
TI  - Structural and thermodynamic studies of the interaction of distamycin A with the
      parallel quadruplex structure [d(TGGGGT)]4.
AB  - The complex between distamycin A and the parallel DNA quadruplex [d(TGGGGT)]4 has
      been studied by 1H NMR spectroscopy and isothermal titration calorimetry (ITC).
      To unambiguously assert that distamycin A interacts with the grooves of the
      quadruplex [d(TGGGGT)]4, we have analyzed the NMR titration profile of a modified
      quadruplex, namely [d(TGGMeGGT)]4, and we have applied the recently developed
      differential frequency-saturation transfer difference (DF-STD) method, for
      assessing the ligand-DNA binding mode. The three-dimensional structure of the 4:1
      distamycin A/[d(TGGGGT)]4 complex has been determined by an in-depth NMR study
      followed by dynamics and mechanics calculations. All results unequivocally
      indicate that distamycin molecules interact with [d(TGGGGT)]4 in a 4:1 binding
      mode, with two antiparallel distamycin dimers that bind simultaneously two
      opposite grooves of the quadruplex. The affinity between distamycin A and
      [d(TGGGGT)]4 enhances ( approximately 10-fold) when the ratio of distamycin A to
      the quadruplex is increased. In this paper we report the first three-dimensional
      structure of a groove-binder molecule complexed to a DNA quadruplex structure.

PMID- 18052172
TI  - Calculations of the effect of tunneling on the Swain-Schaad exponents (SSEs) for
      the 1,5-hydrogen shift in 5-methyl-1,3-cyclopentadiene. Can SSEs be used to
      diagnose the occurrence of tunneling?
AB  - MPW1K density functional calculations, carried out with the 6-31+G(d,p) basis
      set, have been combined with canonical variational transition state theory (CVT)
      and small-curvature tunneling (SCT) corrections in order to compute the primary
      kinetic isotope effects for rearrangement of 5-methyl-1,3-cyclopentadiene (1) to
      1-methyl-1,3-cyclopentadiene (2). The Swain-Schaad exponents, SSE =
      ln(kH/kT)/ln(kD/kT), for this reaction have been computed over the temperature
      range 100-600 K. Tunneling results in both large positive and large negative
      deviations from the value of SSE = 3.26, expected from consideration of only the
      effect of the isotopic mass on passage over the reaction barrier. In the
      rearrangement of 1 to 2, SSE approximately 3.26, not only at temperatures >400 K,
      where tunneling is relatively unimportant, but also around 170 K, where tunneling
      by both H and D is the dominant mode of reaction. Thus, from an experimental
      finding that SSE approximately 3.26 at a single temperature, it cannot be
      rigorously concluded that tunneling is unimportant. Measurement of SSEs over a
      broad temperature range is advisable; but measurement of the temperature
      dependence of just kH/kD can be used to establish more unequivocally whether
      tunneling is important, without the necessity of measuring kT.

PMID- 18052173
TI  - Catalytic asymmetric generation of (Z)-disubstituted allylic alcohols.
AB  - A one-pot method for the direct preparation of enantioenriched (Z)-disubstituted
      allylic alcohols is introduced. Hydroboration of 1-halo-1-alkynes with
      dicyclohexylborane, reaction with t-BuLi, and transmetalation with dialkylzinc
      reagents generate (Z)-disubstituted vinylzinc intermediates. In situ reaction of
      these reagents with aldehydes in the presence of a catalyst derived from (-)-MIB
      generates (Z)-disubstituted allylic alcohols. It was found that the resulting
      allylic alcohols were racemic, most likely due to a rapid addition reaction
      promoted by LiX (X = Br and Cl). To suppress the LiX-promoted reaction, a series
      of inhibitors were screened. It was found that 20-30 mol %
      tetraethylethylenediamine inhibited LiCl without inhibiting the chiral zinc-based
      Lewis acid. In this fashion, (Z)-disubstituted allylic alcohols were obtained
      with up to 98% ee. The asymmetric (Z)-vinylation could be coupled with tandem
      diastereoselective epoxidation reactions to provide epoxy alcohols and allylic
      epoxy alcohols with up to three contiguous stereogenic centers, enabling the
      rapid construction of complex building blocks with high levels of enantio- and
      diastereoselectivity.

PMID- 18052175
TI  - Silylene extrusion from organosilanes via double geminal Si-H bond activation by
      a Cp*Ru(kappa2-P,N)+ complex: observation of a key stoichiometric step in the
      glaser-tilley alkene hydrosilylation mechanism.
AB  - Treatment of Cp*RuCl(kappa2-P,N-2b) (2b = 2-NMe2-3-PiPr2-indene) with TlSO3CF3
      produced the cyclometalated complex [4]+SO3CF3- in 94% isolated yield. Exposure
      of [4]+X- (X = B(C6F5)4 or SO3CF3) to Ph2SiH2 (10 equiv) or PhSiH3 afforded the
      corresponding [Cp*(mu-P,N-2b)(H)2Ru=SiRPh]+X- complexes, [5]+X- (R = Ph; X =
      B(C6F5)4, 82%; X = SO3CF3, 39%) and [6]+X- (R = H; X = B(C6F5)4, 94%; X = SO3CF3,
      95%). Notably, these transformations represent the first documented examples of
      Ru-mediated silylene extrusion via double geminal Si-H bond activation of an
      organosilane-a key step in the recently proposed Glaser-Tilley (G-T) alkene
      hydrosilylation mechanism. Treatment of [5]+B(C6F5)4- with KN(SiMe3)2 or
      [6]+SO3CF3- with NaN(SiMe3)2 afforded the corresponding zwitterionic Cp*(mu-2
      NMe2-3-PiPr2-indenide)(H)2Ru=SiRPh complex in 69% (R = Ph, 7) or 86% (R = H, 8)
      isolated yield. Both [6]+X- and 8 proved unreactive toward 1-hexene and styrene
      and provided negligible catalytic turnover in the attempted metal-mediated
      hydrosilylation of these substrates with PhSiH3, thereby providing further
      empirical evidence for the required intermediacy of base-free Ru=Si species in
      the G-T mechanism. Isomerization of the P,N-indene ligand backbone in [6]+X-,
      giving rise to [Cp*(mu-1-PiPr2-2-NMe2-indene)(H)2Ru=SiHPh]+X- ([9]+X-), was
      observed. In the case of [9]+SO3CF3-, net intramolecular addition of the Ru=Si-H
      group across the styrene-like C=C unit within the ligand backbone to give 10 (96%
      isolated yield) was observed. Crystallographic characterization data are provided
      for [4]+X-, [5]+X-, [6]+X-, 8, and 10.

PMID- 18052174
TI  - Isomeric forms of heavier main group hydrides: experimental and theoretical
      studies of the [Sn(Ar)H]2 (Ar = terphenyl) system.
AB  - A series of symmetric divalent Sn(II) hydrides of the general form [(4-X
      Ar')Sn(mu-H)]2 (4-X-Ar' = C6H2-4-X-2,6-(C6H3-2,6-iPr2)2; X = H, MeO, tBu, and
      SiMe3; 2, 6, 10, and 14), along with the more hindered asymmetric tin hydride
      (3,5-iPr2-Ar*)SnSn(H)2(3,5-iPr2-Ar*) (16) (3,5-iPr2-Ar* = 3,5-iPr2-C6H-2,6-(C6H2
      2,4,6-iPr3)2), have been isolated and characterized. They were prepared either by
      direct reduction of the corresponding aryltin(II) chloride precursors, ArSnCl,
      with LiBH4 or iBu2AlH (DIBAL), or via a transmetallation reaction between an
      aryltin(II) amide, ArSnNMe2, and BH3.THF. Compounds 2, 6, 10, and 14 were
      obtained as orange solids and have centrosymmetric dimeric structures in the
      solid state with long Sn...Sn separations of 3.05 to 3.13 A. The more hindered
      tin(II) hydride 16 crystallized as a deep-blue solid with an unusual, formally
      mixed-valent structure wherein a long Sn-Sn bond is present [Sn-Sn = 2.9157(10)
      A] and two hydrogen atoms are bound to one of the tin atoms. The Sn-H hydrogen
      atoms in 16 could not be located by X-ray crystallography, but complementary
      Mossbauer studies established the presence of divalent and tetravalent tin
      centers in 16. Spectroscopic studies (IR, UV-vis, and NMR) show that, in
      solution, compounds 2, 6, 10, and 14 are predominantly dimeric with Sn-H-Sn
      bridges. In contrast, the more hindered hydrides 16 and previously reported
      (Ar*SnH)2 (17) (Ar* = C6H3-2,6-(C6H2-2,4,6-iPr3)2) adopt primarily the
      unsymmetric structure ArSnSn(H)2Ar in solution. Detailed theoretical calculations
      have been performed which include calculated UV-vis and IR spectra of various
      possible isomers of the reported hydrides and relevant model species. These
      showed that increased steric hindrance favors the asymmetric form ArSnSn(H)2Ar
      relative to the centrosymmetric isomer [ArSn(mu-H)]2 as a result of the widening
      of the interligand angles at tin, which lowers steric repulsion between the
      terphenyl ligands.

PMID- 18052176
TI  - Total synthesis of (-)-salviasperanol.
AB  - The achiral enynone shown cyclized to produce a tricyclic dienone that was
      converted in six steps to (-)-salviasperanol.

PMID- 18052177
TI  - Total synthesis of (+)-komarovispirone.
AB  - (+)-Komaroviquinone photolytically rearranges to (+)-komarovispirone. A
      rationalization of this isomerization is presented.

PMID- 18052178
TI  - Total synthesis of (-)-barbatusol, (+)-demethylsalvicanol, (-)-brussonol, and (+)
      grandione.
AB  - The icetexane-based diterpenes (-)-barbatusol, (+)-demethylsalvicanol, and (-)
      brussonol were synthesized. Synthetic demethylsalvicanol was dimerized to produce
      (+)-grandione using aqueous Diels-Alder conditions.

PMID- 18052179
TI  - Synthesis of the EF-ring of ciguatoxin 3C based on the [2,3]-Wittig rearrangement
      and ring-closing olefin metathesis.
AB  - The EF-ring segment of ciguatoxin 3C, a causative toxin of ciguatera fish
      poisoning, was synthesized in three major steps: 1,4-addition for the C20O-C27
      bond connection, chirality transferring anti selective [2,3]-Wittig rearrangement
      for the construction of the anti-2-hydroxyalkyl ether part, and ring-closing
      olefin metathesis for the F-ring formation.

PMID- 18052180
TI  - Ni-catalyzed mild arylation of alpha-halocarbonyl compounds with arylboronic
      acids.
AB  - A simple yet powerful Ni catalyst can be used to promote direct arylations of
      alpha-halocarbonyl compounds, including a range of esters, amides, and ketones,
      with various arylboronic acids under mild conditions. The method tolerates beta
      hydrogens and functional groups in the substrates and offers reactivity and
      selectivity profiles that are complementary to those found in the well
      established Buchwald-Hartwig approach.

PMID- 18052181
TI  - Organic solvent-free, enantio- and diastereoselective, direct Mannich reaction in
      the presence of water.
AB  - An organocatalyst-mediated, asymmetric Mannich reaction in the presence of water
      without using organic solvents has been developed. A highly reactive
      siloxytetrazole hybrid catalyst has been developed for the reaction of
      dimethoxyacetaldehyde, while the sodium salt of siloxyproline is an effective
      catalyst of alpha-imino glyoxylate. Excellent enantioselectivity can be realized,
      and the usage of organic solvents can be reduced compared to the conventional
      reactions in organic solvents.

PMID- 18052182
TI  - Platinum-catalyzed regio- and stereoselective arylthiolation of internal alkynes.
AB  - Unsymmetrical internal alkynes such as ethyl phenylpropiolate (2b) successfully
      underwent Pt-catalyzed decarbonylative arylthiolation by thioesters. The regio-
      and stereoselective insertion of 2b into an S-Pt bond was confirmed by reaction
      with a platinum complex with an S-Pt-Cl framework.

PMID- 18052183
TI  - Dramatic solvent effect on the diastereoselectivity of Michael addition: study
      toward the synthesis of the ABC ring system of hexacyclinic acid.
AB  - During our studies toward the synthesis of the ABC ring system of hexacyclinic
      acid, we have observed a dramatic influence of the solvent on both our key steps.
      The diastereoselectivity of the intermolecular Michael addition could be totally
      reversed by changing the polarity of the solvent, and trifluoroethanol was found
      to be the optimal solvent for the following Mn(III)-promoted radical cyclization.

PMID- 18052184
TI  - A nucleophilic Fe catalyst for transesterifications under neutral conditions.
AB  - Carboxylic esters belong to the most important functional groups in organic
      chemistry. Strong efforts have been made in developing mild catalytic procedures
      for their preparation. Among the various methods developed to date,
      transesterifications have occupied an important space. In the present paper, a
      new catalytic method for this process based on the use of nucleophilic Fe(-II)
      complexes is presented. Evidence for the formation of an intermediate acyl Fe
      complex will be presented as well as investigations on scope and limitations.

PMID- 18052185
TI  - Cycloaddition/Ring opening reaction sequences of N-alkenyl aziridines: influence
      of the aziridine nitrogen on stereoselectivity.
AB  - The cycloaddition of (Z)-7-(prop-1-enyl)-7-azabicyclo[4.1.0]heptane with dimethyl
      acetylene dicarboxylate (DMAD) was reported previously to proceed with complete
      stereoselectivity. Quantum chemical calculations (B3LYP) were used to evaluate
      the mechanism of the cyclization process, and it was discovered that a stepwise
      pathway is preferred. The subsequent electrocyclic ring opening reaction of the
      cyclobutene was also studied, and it was found that ring opening to the "methyl
      in" dienamine is preferred to the "methyl-out" product by some 4-5 kcal/mol.

PMID- 18052186
TI  - Polyene cyclization promoted by the cross-conjugated alpha-carbalkoxy enone
      system. Observation on a putative 1,5-hydride/1,3-alkyl shift under Lewis acid
      catalysis.
AB  - Polyene cyclization of compounds 3 and 4 under catalysis with AlCl3 and/or SnCl4
      gave rise to complex bicyclic products 8 and 9, structures of which were highly
      unexpected, and X-ray analyses were invoked for unambiguously structural
      identification. Mechanistically, a tandem sigma-bond rearrangement process,
      including an unusual through-space 1,5-hydride or 1,3-alkyl shift as a key
      operation, is proposed.

PMID- 18052187
TI  - Oxazaborolidinone-promoted vinylogous Mukaiyama aldol reactions.
AB  - delta-Hydroxy-alpha,beta-unsaturated carbonyl compounds were prepared in one step
      via the vinylogous Mukaiyama aldol reactions with O,O-silyl ketene acetals.
      Isopropyl alcohol as additive and tryptophane-based B-phenyloxazaborolidinone
      were required for obtaining the gamma-alkylated product in high
      enantioselectivities.

PMID- 18052188
TI  - Using dynamic gene module map analysis to identify targets that modulate free
      fatty acid induced cytotoxicity.
AB  - The objective of this study was to identify pathways that regulate the
      cytotoxicity induced by free fatty acids (FFAs) in human hepatoblastoma cells
      (HepG2/C3A). Gene expression profiles of HepG2/C3A cells were obtained at three
      time points, after 24, 48, and 72 h of exposure to different types of FFA.
      Saturated fatty acid (palmitate) was found to be cytotoxic. The pathways
      activated by the different FFAs at the different time points were identified
      using global gene module map analysis. Unsaturated FFAs exerted transcriptional
      regulation mainly within the first 24 h, whereas saturated FFA, palmitate,
      regulated energy production pathways, such as the electron transport chain (ETC)
      and tricarboxylic acid cycle, within the first 24 h. In the next 24 h, palmitate
      up-regulated 36 cell death relevant pathways and down-regulated several
      protective pathways, such as the pentose phosphate pathway and glutathione
      related pathways. In the final 24 h, the FFAs did not induce significant
      transcriptional regulation. We hypothesized that palmitate induced cytotoxicity
      by first perturbing metabolic pathways in the initial 24 h, resulting in changes
      to factors, such as metabolites or signaling molecules, which subsequently
      triggered cell death relevant pathways in the next 24 h. The uptake and release
      of 27 metabolites were measured to further elucidate the metabolic changes in the
      first 24 h. It was determined that ketone bodies such as beta-hydroxybutyrate and
      acetoacetate were important in separating the toxic from the nontoxic phenotypes.
      A regression model was used to identify the genes relevant to these metabolites.
      Some of the genes identified to be important were experimentally validated. It
      was found that ETC genes such as NADH dehydrogenase and succinate dehydrogenase
      were involved in palmitate induced cytotoxicity.

PMID- 18052189
TI  - Efficient synthesis of [2'-18O]uridine and its incorporation into
      oligonucleotides: a new tool for mechanistic study of nucleotidyl transfer
      reactions by isotope effect analysis.
AB  - Lack of sufficient quantities of isotopically labeled materials has precluded the
      use of heavy atom isotope effects to investigate mechanisms of nucleotidyl
      transfer reactions in nucleic acids. Here we achieve regioselective opening of
      2,2'-cyclouridine with [(18)O2]benzoic acid/potassium hydride, allowing an
      efficient "one-pot" synthesis of [2'-18O]uridine in 88% yield. Conversion to the
      corresponding phosphoramidite enables solid-phase synthesis of [2'-(18)O] RNA
      substrates for isotope effect studies with nucleotidyl transferases and
      hydrolases.

PMID- 18052190
TI  - Thermal decomposition of methyl butanoate: ab initio study of a biodiesel fuel
      surrogate.
AB  - In this paper, we report a detailed analysis of the breakdown kinetic mechanism
      for methyl butanoate (MB) using theoretical approaches. Electronic structures and
      structure-related molecular properties of reactants, intermediates, products, and
      transition states were explored at the BH&HLYP/cc-pVTZ level of theory. Rate
      constants for the unimolecular and bimolecular reactions in the temperature range
      of 300-2500 K were calculated using Rice-Ramsperger-Kassel-Marcus and transition
      state theories, respectively. Thirteen pathways were identified leading to the
      formation of small compounds such as CH(3), C(2)H(3), CO, CO(2), and H(2)CO. For
      the initial formation of MB radicals, H, CH(3), and OH were considered as
      reactive radicals participating in hydrogen abstraction reactions. Kinetic
      simulation results for a high temperature pyrolysis environment show that MB
      radicals are mainly produced through hydrogen abstraction reactions by H atoms.
      In addition, the C(O)OCH(3) = CO + CH(3)O reaction is found to be the main source
      of CO formation. The newly computed kinetic sub-model for MB breakdown is
      recommended as a core component to study the combustion of oxygenated species.

PMID- 18052191
TI  - Conjugation of nucleosides and oligonucleotides by [3+2] cycloaddition.
AB  - A procedure is presented for copper(I)-catalyzed [3+2] cycloaddition of
      nucleosides and nucleotides in near-quantitative yield. Azido-alkyne
      cycloaddition was applied for the preparation of a range of adenosine dimers and
      derivatives with versatile functionality, as well as for the smooth condensation
      of two oligonucleotide strands. The described technology may find valuable
      application in the synthesis of oligonucleotide dimers and conjugates.

PMID- 18052192
TI  - Mechanism of thiolate-disulfide interchange reactions in biochemistry.
AB  - Both density functional theory (DFT) (B3LYP) and CCSD ab initio calculations were
      employed in a theoretical investigation of the mechanism of thiolate-disulfide
      exchange reactions. The reaction pathway for degenerate thiolate-disulfide
      exchange reactions with dimethyl disulfide has been shown to proceed through a
      SN2-like transition structure that is very close in energy to the corresponding
      trisulfur anionic intermediate ([delta-S-S-Sdelta(-)]). When relatively small
      substituents are involved, the level of theory must be increased to CCSD to make
      this rather subtle mechanistic distinction. With the more sterically hindered
      exchange reaction involving t-butyl mercaptide and di-t-butyl disulfide, the
      potential energy surface exhibits a distinct preference for the S(N)2
      displacement pathway with an activation barrier of 9.8 kcal/mol. When corrections
      for solvent polarity are included (COSMO), an S(N)2 mechanism is also implicated
      in both polar and nonpolar solvents. DFT studies on thiolate-disulfide exchange,
      when the substituent is a model peptide, strongly support the intermediacy of a
      trisulfur intermediate that lies 10.7 kcal/mol below isolated reactants. A well
      depth of this magnitude should provide a sufficient lifetime of the intermediate
      to accommodate the requisite conformational adjustments that accompanies
      formation of the new disulfide bond.

PMID- 18052193
TI  - A facile synthesis of new 5H-indazolo[3,2-b]benzo[d]-1,3-oxazines via one-pot
      intramolecular Bis-heterocyclizations.
AB  - The parent 5H-indazolo[3,2-b]benzo[d]-1,3-oxazine heterocycle as well as a series
      of novel analogues have been synthesized utilizing two subsequent intramolecular
      heterocyclizations in one pot. A variety of diversity groups were added to
      explore the scope of this reaction and to provide a number of new compounds for
      biological screening.

PMID- 18052194
TI  - Carbocyclization reaction of omega-iodo- and 1,omega-diiodo-1-alkynes without the
      loss of iodine atoms through a carbenoid-chain process.
AB  - Atom-economical carbocyclization reactions of omega-iodo-1-alkynes and 1,omega
      diiodo-1-alkynes to give products with incorporation of iodine atoms is
      described. Cycloisomerization of 2-(2-propynyloxy)ethyl iodides is initiated by a
      catalytic amount of LDA to give 3-(iodomethylene)tetrahydrofurans in high yields.
      Upon treatment of with a catalytic amount of 1-hexynyllithium, 1,omega-diiodo-1
      alkynes efficiently undergo cycloisomerization to give
      (diiodomethylene)cycloalkanes. The diiodomethylene products are also obtained by
      iodine atom-transfer-type cyclization of omega-iodo-1-alkynes, using 1-iodo-1
      hexyne as an external iodine atom source. Bromine atom-transfer and proton
      transfer cyclization proceed as well by employing 1-bromo-1-octyne and 1-octyne,
      respectively. These reactions are proposed to proceed through a carbenoid-chain
      process involving exo-cyclization of the lithium acetylide intermediates to give
      Li,I-alkylidene carbenoids. It is shown that the exo-cyclization proceeded
      stereospecifically through inversion of the stereochemistry at the electrophilic
      carbon.

PMID- 18052195
TI  - Insights into a mutation-assisted lateral drug escape mechanism from the HIV-1
      protease active site.
AB  - We provide insight into the first stages of a kinetic mechanism of lateral drug
      expulsion from the active site of HIV-1 protease, by conducting all atom
      molecular dynamics simulations with explicit solvent over a time scale of 24 ns
      for saquinavir bound to the wildtype, G48V, L90M and G48V/L90M mutant proteases.
      We find a consistent escape mechanism associated with the G48V mutation. First,
      increased hydrophilic and hydrophobic flap coupling and water mediated disruption
      of catalytic dyad hydrogen bonding induce drug motion away from the dyad and
      promote protease flap transition to the semi-open form. Conversely, flap
      inhibitor motion is decoupled in the wildtype. Second, the decrease of total
      interactions causes unidirectional lateral inhibitor translation by up to 4 A
      toward the P3 subsite exit of the active site, increased P3 subsite exposure to
      solvent and a complete loss of hydrophobic interactions with the opposite end of
      the active site. The P1 subsite moves beyond the hydrophobic active site side
      pocket, the only remaining steric barrier to complete expulsion being the
      "breathable" residue, P81. Significant inhibitor deviation is reported over 24
      ns, and subsequent complete expulsion, implemented using steered molecular
      dynamics simulations, is shown to occur most easily for the G48V-containing
      mutants. Our simulations thus provide compelling support for lateral drug escape
      from a protease in a semi-open flap conformation. It is likely that some
      mutations take advantage of this escape mechanism to increase the rate of
      inhibitor dissociation from the protease. Finally, unidirectional translation may
      be countered by designing inhibitors with terminal subsites that provide
      sufficient anchoring to the flaps, thus increasing the steric barrier for
      translation in either direction.

PMID- 18052196
TI  - Metal requirements and phosphodiesterase activity of tRNase Z enzymes.
AB  - The endonuclease tRNase Z from A. thaliana (AthTRZ1) was originally isolated for
      its tRNA 3' processing activity. Here we show that AthTRZ1 also hydrolyzes the
      phosphodiester bond in bis(p-nitrophenyl) phosphate (bpNPP) with a kcat of 7.4 s
      1 and a KM of 8.5 mM. We analyzed 22 variants of AthTRZ1 with respect to their
      ability to hydrolyze bpNPP. This mutational mapping identified fourteen variants
      that lost the ability to hydrolyze bpNPP and seven variants with reduced
      activity. Surprisingly, a single amino acid change (R252G) resulted in a ten
      times higher activity compared to the wild type enzyme. tRNase Z enzymes exist in
      long and short forms. We show here that in contrast to the short tRNase Z enzyme
      AthTRZ1, the long tRNase Z enzymes do not have bpNPP hydrolysis activity pointing
      to fundamental differences in substrate cleavage between the two enzyme forms.
      Furthermore, we determined the metal content of AthTRZ1 and analyzed the metal
      requirement for bpNPP hydrolysis. AthTRZ1 shows a high affinity for Zn2+ ions;
      even upon incubation with metal chelators, 0.76 Zn2+ ions are retained per dimer.
      In contrast to bpNPP hydrolysis, pre-tRNA processing requires additional metal
      ions, Mn2+ or Mg2+, as Zn2+ ions alone are insufficient.

PMID- 18052197
TI  - Multiple cysteine residues are implicated in Janus kinase 2-mediated catalysis.
AB  - The redox regulation of Janus kinase 2 (JAK2) is poorly understood, and there are
      contradictory reports as to whether the enzyme's activity is inhibited or
      stimulated by oxidizing conditions in the cell. Here we demonstrate that multiple
      cysteine residues within the JAK2 catalytic domain may be crucial for enzymatic
      activity. The enzyme is catalytically inactive when oxidized; activity can be
      restored via reduction to the thiol state. A series of recombinant variants of
      JAK2 were overproduced using the baculoviral expression vector system. A
      truncated variant of JAK2, GST/(NDelta661)rJAK2, provided evidence that the amino
      terminal autoinhibitory domain was not essential for direct redox regulation and
      that only nine cysteine residues were potentially involved. The effect of
      individually and combinatorially altering these nine cysteines was examined via
      cysteine-to-serine mutagenesis. This identified four cysteine residues in the
      catalytic domain (Cys866, Cys917, Cys1094, and Cys1105) that cooperatively
      maintain JAK2's catalytic competency. Our data are consistent with a direct
      mechanism for redox regulation of JAK2 via oxidation and reduction of critical
      cysteine residues.

PMID- 18052198
TI  - Interesting structural and dynamical behaviors exhibited by the AF-6 PDZ domain
      upon Bcr peptide binding.
AB  - PDZ (postsynaptic density-95, disks large, zonula occludens-1) domains are small,
      protein-protein interaction modules that have multiple binding surfaces for the
      docking of diverse molecules. These domains can propagate signals from ligand
      binding site to distal regions of the structure through allosteric communication.
      Recent works have revealed that picosecond to nanosecond time scale dynamics play
      a potential role in propagating long-range signals within a protein. Comparison
      of AF-6 PDZ domain structures in free and complex forms shows a conformation
      rearrangement of distal surface 2, which is far from the peptide binding groove.
      The relaxation dispersion experiments detected that the free AF-6 PDZ domain was
      sampling multiple conformations; millisecond dynamics mapped a network for
      allostery signal transmission throughout the AF-6 PDZ domain in the weak
      saturation state, and intramolecular motions were observed in distal surface 1
      when the protein was saturated. These results provide evidence that the
      allosteric process in the AF-6 PDZ domain is not two-state; instead, the
      millisecond dynamic network provides a mechanism for the transmission of
      allosteric signals throughout a protein. Interestingly, the two distal surfaces
      of the AF-6 PDZ domain respond differently to peptide binding; distal surface 1
      changes in millisecond dynamics, whereas distal surface 2 undergoes structural
      rearrangement. The significance of the different response patterns in the
      signaling pathway and its relevance to the function of the AF-6 PDZ domain should
      be studied further.

PMID- 18052199
TI  - Features of transmembrane segments that promote the lateral release from the
      translocase into the lipid phase.
AB  - Topogenic sequences direct the membrane topology of proteins by being recognized
      and decoded by integral membrane translocases. In this paper, we have compared
      the minimal sequence characteristics of helical-hairpin, reverse signal-anchor,
      and stop-transfer sequences in bacterial membrane proteins that use either the
      YidC or SecYEG translocases for membrane insertion. We find that a stretch
      composed of 3 leucines and 16 alanines is required for efficient membrane
      anchoring of the M13 procoat protein that inserts by a helical hairpin mechanism,
      and that a stretch composed of only 19 alanines has a detectable membrane
      anchoring ability. Similar results were obtained for the reverse signal-anchor
      sequence of the single-spanning Pf3 coat protein and for stop-transfer segments
      engineered into leader peptidase. We have also determined the contribution to the
      apparent free energy of membrane insertion of M13 procoat for all 20 amino acids.
      The relative order of the contributions is similar to that determined for a stop
      transfer sequence in the mammalian endoplasmic reticulum, but the absolute
      difference between the contributions for the most hydrophobic and most
      hydrophilic residues is somewhat larger in the E. coli system. These results are
      significant because they define the features of a membrane protein transmembrane
      segment that induce lateral release from the YidC and Sec translocases into the
      lipid bilayer in bacteria.

PMID- 18052200
TI  - Dynamics of backbone conformational heterogeneity in Bacillus subtilis
      ribonuclease P protein.
AB  - Interconversion of protein conformations is imperative to function, as evidenced
      by conformational changes associated with enzyme catalytic cycles, ligand binding
      and post-translational modifications. In this study, we used 15N NMR relaxation
      experiments to probe the fast (i.e., ps-ns) and slow (i.e., micros-ms)
      conformational dynamics of Bacillus subtilis ribonuclease P protein (P protein)
      in its folded state, bound to two sulfate anions. Using the Lipari-Szabo mapping
      method [Andrec, M., Montelione, G. T., and Levy, R. M. (2000) J. Biomol. NMR 18,
      83-100] to interpret the data, we find evidence for P protein dynamics on the mus
      ms time scale in the ensemble. The residues that exhibit these slow internal
      motions are found in regions that have been previously identified as part of the
      P protein-P RNA interface. These results suggest that structural flexibility
      within the P protein ensemble may be important for proper RNase P holoenzyme
      assembly and/or catalysis.

PMID- 18052201
TI  - Reaction center of photosystem II with no peripheral pigments in D2 allows
      secondary electron transfer in D1.
AB  - A pigment-deficient reaction center of photosystem II (PSII)-with all the core
      pigments (two molecules of chlorophyll a and one of pheophytin a in each D
      protein) but with only one molecule each of peripheral chlorophyll a (Chlz) and
      beta-carotene (Car)-has been investigated by pump-probe spectroscopy. The data
      imply that Car and Chlz are both bound to D1. The absence of Car and Chlz in D2
      allows the unprecedented observation of secondary electron transfer in D1 of PSII
      reaction centers at room temperature. The absorption band of the Car cation in D1
      (Car(D1)(+*)) peaks around 910 nm (as against 990 nm for Car(D2)(+*)), and its
      positive hole is shared by ChlzD1, whereas Car(D2)(+*) can disappear by capturing
      an electron from ChlzD2.

PMID- 18052202
TI  - Crystal structure of a type II dihydrofolate reductase catalytic ternary complex.
AB  - Type II dihydrofolate reductase (DHFR) is a plasmid-encoded enzyme that confers
      resistance to bacterial DHFR-targeted antifolate drugs. It forms a symmetric
      homotetramer with a central pore which functions as the active site. Its unusual
      structure, which results in a promiscuous binding surface that accommodates
      either the dihydrofolate (DHF) substrate or the NADPH cofactor, has constituted a
      significant limitation to efforts to understand its substrate specificity and
      reaction mechanism. We describe here the first structure of a ternary R67
      DHFR.DHF.NADP+ catalytic complex, resolved to 1.26 A. This structure provides the
      first clear picture of how this enzyme, which lacks the active site carboxyl
      residue that is ubiquitous in Type I DHFRs, is able to function. In the catalytic
      complex, the polar backbone atoms of two symmetry-related I68 residues provide
      recognition motifs that interact with the carboxamide on the nicotinamide ring,
      and the N3-O4 amide function on the pteridine ring. This set of interactions
      orients the aromatic rings of substrate and cofactor in a relative endo geometry
      in which the reactive centers are held in close proximity. Additionally, a
      central, hydrogen-bonded network consisting of two pairs of Y69-Q67-Q67'-Y69'
      residues provides an unusually tight interface, which appears to serve as a
      "molecular clamp" holding the substrates in place in an orientation conducive to
      hydride transfer. In addition to providing the first clear insight regarding how
      this extremely unusual enzyme is able to function, the structure of the ternary
      complex provides general insights into how a mutationally challenged enzyme,
      i.e., an enzyme whose evolution is restricted to four-residues-at-a-time active
      site mutations, overcomes this fundamental limitation.

PMID- 18052203
TI  - Tropomyosin's periods are quasi-equivalent for actin binding but have specific
      regulatory functions.
AB  - Tropomyosin is a coiled coil that associates N-terminus to C-terminus to form a
      continuous strand along both sides of the actin filament and regulates its
      function. One long, high molecular weight tropomyosin molecule spans the length
      of seven actin subunits. In these forms there is a 7-fold periodicity in
      noninterface residues that have been proposed to correspond to seven quasi
      equivalent actin binding sites. Interruption of the stable, canonical coiled coil
      by residues that destabilize the interhelical interface, such as Ala clusters, is
      required for actin binding. Previous studies have shown that the N-terminal half
      of period 5 (residues 165-188) is critical for actin binding and regulatory
      function and that both the surface "consensus" residues and the embedded,
      destabilizing Ala cluster are required for function. In the present work we test
      the hypothesis of quasi-equivalence of tropomyosin's periodic sites by replacing
      the proposed binding sites by substituting the crucial period 5 region with
      regions of period 1 or 2. Replacement mutants were designed to test the
      importance of the coincidence of the consensus residues and a destabilizing
      interface. The results show that generic (interface instability) and specific
      periodic surface residues are essential for function and that the periods tested
      (periods 1, 2, and 5) are quasi-equivalent for actin binding. However, regulatory
      functions are period-specific: periods 1 and 5 for binding to actin in the force
      producing state and period 5 for Ca2+-dependent regulation with troponin.

PMID- 18052204
TI  - Quadruplex-coupled kinetics distinguishes ligand binding between G4 DNA motifs.
AB  - G-quadruplex (or G4 DNA) specific ligands are important potential anticancer
      molecules as telomerase inhibitors. On the other hand, emerging evidence
      implicates G4 DNA in regulation of several oncogenes making telomerase inhibitors
      amenable to undesired effects (Borman, S. (2007) Chem. Eng. News 85 (22), 12-17).
      Therefore molecules which can discriminate between G4 DNA are of interest, both
      as telomerase inhibitors and for selective intervention of gene expression.
      Design of selective molecules requires resolution of the coupled equilibria
      between intramolecular quadruplex-formation and bimolecular ligand-binding.
      Several previous studies have reported G4-ligand binding kinetics, however the
      primary equilibrium of intramolecular G4 DNA folding/unfolding was not
      considered. Here, we quantitatively assess the linked equilibrium in G4-ligand
      complexes using a novel real time surface plasmon resonance-based technique.
      Kinetic constants for G4 folding/unfolding and ligand binding were simultaneously
      determined, for the first time, from a single reaction by resolving the coupled
      equilibrium. We demonstrate the coupled model by showing that affinity of TMPyP4
      (a well-established anticancer telomerase inhibitor) for the human telomere
      quadruplex is only 3-fold more than the c-MYC promoter G4, which is known to
      repress c-MYC. This provides quantitative rationale to poor selectivity of TMPyP4
      in recently observed cell-based assays. In the light of recent advances
      indicating G4's regulatory potential in several important genes, quantitative
      evaluation of selectivity vis-a-vis affinity as presented here will augment
      design and preliminary screening of new molecules.

PMID- 18052205
TI  - Low-temperature pulsed EPR study at 34 GHz of the triplet states of the primary
      electron Donor P865 and the carotenoid in native and mutant bacterial reaction
      centers of Rhodobacter sphaeroides.
AB  - The photosynthetic charge separation in bacterial reaction centers occurs
      predominantly along one of two nearly symmetric branches of cofactors. Low
      temperature EPR spectra of the triplet states of the chlorophyll and carotenoid
      pigments in the reaction center of Rhodobacter sphaeroides R-26.1, 2.4.1 and two
      double-mutants GD(M203)/AW(M260) and LH(M214)/AW(M260) have been recorded at 34
      GHz to investigate the relative activities of the "A" and "B" branches. The
      triplet states are found to derive from radical pair and intersystem crossing
      mechanisms, and the rates of formation are anisotropic. The former mechanism is
      operative for Rb. sphaeroides R-26.1, 2.4.1, and mutant GD(M203)/AW(M260) and
      indicates that A-branch charge separation proceeds at temperatures down to 10 K.
      The latter mechanism, derived from the spin polarization and operative for mutant
      LH(M214)/AW(M260), indicates that no long-lived radical pairs are formed upon
      direct excitation of the primary donor and that virtually no charge separation at
      the B-branch occurs at low temperatures. When the temperature is raised above 30
      K, B-branch charge separation is observed, which is at most 1% of A-branch charge
      separation. B-branch radical pair formation can be induced at 10 K with low yield
      by direct excitation of the bacteriopheophytin of the B-branch at 590 nm. The
      formation of a carotenoid triplet state is observed. The rate of formation
      depends on the orientation of the reaction center in the magnetic field and is
      caused by a magnetic field dependence of the oscillation frequency by which the
      singlet and triplet radical pair precursor states interchange. Combination of
      these findings with literature data provides strong evidence that the thermally
      activated transfer step on the B-branch occurs between the primary donor, P865,
      and the accessory bacteriochlorophyll, whereas this step is barrierless down to
      10 K along the A-branch.

PMID- 18052207
TI  - A new use for a familiar fold: the X-ray crystal structure of GTP-bound GTP
      cyclohydrolase III from Methanocaldococcus jannaschii reveals a two metal ion
      catalytic mechanism.
AB  - GTP cyclohydrolase (GCH) III from Methanocaldococcus jannaschii, which catalyzes
      the conversion of GTP to 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone
      5'-phosphate (FAPy), has been shown to require Mg2+ for catalytic activity and is
      activated by monovalent cations such as K+ and ammonium [Graham, D. E., Xu, H.,
      and White, R. H. (2002) Biochemistry 41, 15074-15084]. The reaction is formally
      identical to that catalyzed by a GCH II ortholog (SCO 6655) from Streptomyces
      coelicolor; however, SCO 6655, like other GCH II proteins, is a zinc-containing
      protein. The structure of GCH III complexed with GTP solved at 2 A resolution
      clearly shows that GCH III adopts a distinct fold that is closely related to the
      palm domains of phosphodiesterases, such as DNA polymerase I. GCH III is a
      tetramer of identical subunits; each monomer is composed of an N- and a C
      terminal domain that adopt nearly superimposible structures, suggesting that the
      protein has arisen by gene duplication. Three metal ions were located in the
      active site, two of which occupy positions that are analogous to those occupied
      by divalent metal ions in the structures of a number of palm domain containing
      proteins, such as DNA polymerase I. Two conserved Asp residues that coordinate
      the metal ions, which are also found in palm domain containing proteins, are
      observed in GCH III. Site-directed variants (Asp-->Asn) of these residues in GCH
      III are less active than wild-type. The third metal ion, most likely a potassium
      ion, is involved in substrate recognition through coordination of O6 of GTP. The
      arrangement of the metal ions in the active site suggests that GCH III utilizes
      two metal ion catalysis. The structure of GCH III extends the repertoire of
      possible reactions with a palm fold to include cyclohydrolase chemistry.

PMID- 18052208
TI  - Vinflunine, a novel microtubule inhibitor, suppresses calmodulin interaction with
      the microtubule-associated protein STOP.
AB  - Vinca alkaloids vinblastine and vincristine and some of their derivatives such as
      vinorelbine are widely used in therapy of leukemia and several solid tumors.
      Their action is associated with alterations of the mitotic spindle functions that
      prevent the cell cycle progression and lead to mitotic block. A number of studies
      show that some Vinca alkaloids inhibit CaM-target interaction. The newest
      microtubule inhibitor, vinflunine (Javlor), currently in clinical trials, is
      remarkably more active than vinblastine against a number of tumors. Moreover,
      vinflunine is significantly less toxic than other Vinca alkaloids. The high
      antitumor activity of this molecule is not well understood since it binds to
      tubulin with an overall affinity several-fold lower than that of vinblastine or
      vincristine. In this study, we examined the interaction of Ca2+-CaM with
      vinflunine, vinblastine, and stable tubule only polypeptide (STOP) by using a
      combination of thermodynamic and mass spectrometric approaches. We characterized
      the influence of Vinca alkaloids on Ca2+-CaM-STOP complex formation. Our results
      revealed different binding modes to Ca2+-CaM for vinflunine and vinblastine,
      highlighting that adding fluorine atoms on the cleavamine moiety of the Vinca
      alkaloid molecule is critical for the localization of the drug on calmodulin. We
      demonstrate that vinflunine is a better inhibitor for STOP binding to calmodulin
      than vinblastine. We suggest that vinflunine action on calmodulin can have an
      effect on microtubule dynamics. These data may contribute to a better
      understanding of the superior antitumor efficiency and lower toxicity of
      vinflunine.

PMID- 18052209
TI  - Fructose-1,6-bisphosphate acts both as an inducer and as a structural cofactor of
      the central glycolytic genes repressor (CggR).
AB  - CggR is the transcriptional repressor of the gapA operon encoding central
      glycolytic enzymes in Bacillus subtilis. Recently, a detailed mechanistic
      characterization of gapA induction revealed that the binding of fructose-1,6
      bisphosphate (FBP) to a low affinity site on CggR (Kd > 100 microM) is
      responsible for repressor release from the DNA. In addition, this prior work
      demonstrated that FBP binds to a second high affinity site on the repressor,
      causing a conformational change in the CggR/DNA complexes, but with no
      consequence on CggR affinity for its operator DNA. In the present study we have
      thoroughly analyzed the structural and thermodynamic consequences of FBP binding
      to CggR. Results of fluorescence anisotropy titrations, calorimetry and limited
      proteolysis confirm the existence in CggR of a high affinity site for FBP, with a
      Kd of around 6 microM. Using analytical size-exclusion chromatography,
      ultracentrifugation as well as fluorescence correlation spectroscopy (FCS) and
      pressure perturbation, we show that FBP binding at this site reduces the size of
      the CggR oligomers and induces conformational changes that stabilize the dimer
      against denaturation. Hence, FBP has a dual role on CggR structure and regulatory
      function. In addition to acting as an inducer of transcription at the low
      affinity site, FBP bound to the high affinity site acts as a structural cofactor
      for the repressor, with profound effects on its quaternary structure as well as
      on its conformational dynamics and stability. This high affinity FBP site
      apparently evolved from the sugar substrate binding site of homologous enzymes.

PMID- 18052210
TI  - Purification of the human alpha2 Isoform of Na,K-ATPase expressed in Pichia
      pastoris. Stabilization by lipids and FXYD1.
AB  - Human alpha1 and alpha2 isoforms of Na,K-ATPase have been expressed with porcine
      10*Histidine-tagged beta1 subunit in Pichia pastoris. Methanol-induced expression
      of alpha2 is optimal at 20 degrees C, whereas at 25 degrees C, which is optimal
      for expression of alpha1, alpha2 is not expressed. Detergent-soluble alpha2beta1
      and alpha1beta1 complexes have been purified in a stable and functional state.
      alpha2beta1 shows a somewhat lower Na,K-ATPase activity and higher K0.5K compared
      to alpha1beta1, while values of K0.5Na and KmATP are similar. Ouabain inhibits
      both alpha1beta1 (K0.5 24.6 +/- 6 nM) and alpha2beta1 (K0.5 102 +/- 14 nM) with
      high affinity. A striking difference between the isoforms is that alpha2beta1 is
      unstable. Both alpha1beta1 and alpha2beta1 complexes, prepared in C12E8 with an
      added phosphatidyl serine, are active, but alpha2beta1 is rapidly inactivated at
      0 degrees C. Addition of low concentrations of cholesterol with 1-stearoyl-2
      oleoyl-sn-glycero-3-[phospho-l-serine] (SOPS) stabilizes strongly, maintaining
      alpha2beta1 active up to two weeks at 0 degrees C. By contrast, alpha1beta1 is
      stable at 0 degrees C without added cholesterol. Both alpha1beta1 and alpha2beta1
      complexes are stabilized by cholesterol at 37 degrees C. Human FXYD1
      spontaneously associates in vitro with either alpha1beta1 or alpha2beta1, to form
      alpha1beta1/FXYD1 and alpha2beta1/FXYD1 complexes. The reconstituted FXYD1
      protects both alpha1beta1 and alpha2beta1 very strongly against thermal
      inactivation. Instability of alpha2 is attributable to suboptimal
      phophatidylserine-protein interactions. Residues within TM8, TM9 and TM10, near
      the alphabeta subunit interface, may play an important role in differential
      interactions of lipid with alpha1 and alpha2, and affect isoform stability.
      Possible physiological implications of isoform interactions with phospholipids
      and FXYD1 are discussed.

PMID- 18052211
TI  - Structure and orientation of pancreatic colipase in a lipid environment: PM-IRRAS
      and Brewster angle microscopy studies.
AB  - Colipase is a key element in lipase-catalyzed dietary lipids hydrolysis. Although
      devoid of enzymatic activity, colipase promotes pancreatic lipase activity in the
      physiological intestinal conditions by anchoring the enzyme on the surface of
      lipid droplets. Polarization modulation infrared reflection absorption
      spectroscopy combined with Brewster angle microscopy studies was performed on
      colipase alone and in various lipid environments to obtain a global view of both
      conformation and orientation and to assess lipid perturbations. We clearly show
      that colipase fully inserts into a dilaurin monolayer and promotes the formation
      of lipid/protein domains, whereas in a phospholipid environment its insertion is
      only partial, limited to the polar head group. In a mixed 70%
      phosphatidylcholine/30% dilaurin environment, colipase adsorbs to but does not
      penetrate deeply into the film. It triggers the formation of diglyceride domains
      under which it would form a rather uniform layer. We also clearly demonstrate
      that colipase adopts a preferred orientation when dilaurin is present at the
      interface. In contrast, at a neutral phospholipid interface, the infrared spectra
      suggest an isotropic orientation of colipase which could explain its incapacity
      to reverse the inhibitory effects of these lipids on the lipase activity.

PMID- 18052212
TI  - Swiveling domain mechanism in pyruvate phosphate dikinase.
AB  - Pyruvate phosphate dikinase (PPDK) catalyzes the reversible conversion of
      phosphoenolpyruvate (PEP), AMP, and Pi to pyruvate and ATP. The enzyme contains
      two remotely located reaction centers: the nucleotide partial reaction takes
      place at the N-terminal domain, and the PEP/pyruvate partial reaction takes place
      at the C-terminal domain. A central domain, tethered to the N- and C-terminal
      domains by two closely associated linkers, contains a phosphorylatable histidine
      residue (His455). The molecular architecture suggests a swiveling domain
      mechanism that shuttles a phosphoryl group between the two reaction centers. In
      an early structure of PPDK from Clostridium symbiosum, the His445-containing
      domain (His domain) was positioned close to the nucleotide binding domain and did
      not contact the PEP/pyruvate-binding domain. Here, we present the crystal
      structure of a second conformational state of C. symbiosum PPDK with the His
      domain adjacent to the PEP-binding domain. The structure was obtained by
      producing a three-residue mutant protein (R219E/E271R/S262D) that introduces
      repulsion between the His and nucleotide-binding domains but preserves viable
      interactions with the PEP/pyruvate-binding domain. Accordingly, the mutant enzyme
      is competent in catalyzing the PEP/pyruvate half-reaction but the overall
      activity is abolished. The new structure confirms the swivel motion of the His
      domain. In addition, upon detachment from the His domain, the two nucleotide
      binding subdomains undergo a hinge motion that opens the active-site cleft. A
      similar hinge motion is expected to accompany nucleotide binding (cleft closure)
      and release (cleft opening). A model of the coupled swivel and cleft opening
      motions was generated by interpolation between two end conformations, each with
      His455 positioned for phosphoryl group transfer from/to one of the substrates.
      The trajectory of the His domain avoids major clashes with the partner domains
      while preserving the association of the two linker segments.

PMID- 18052214
TI  - Conformational specificity of the lac repressor coiled-coil tetramerization
      domain.
AB  - Predictive understanding of how the folded, functional shape of a native protein
      is encoded in the linear sequence of its amino acid residues remains an unsolved
      challenge in modern structural biology. Antiparallel four-stranded coiled coils
      are relatively simple protein structures that embody a heptad sequence repeat and
      rich diversity for tertiary packing of alpha-helices. To explore specific
      sequence determinants of the lac repressor coiled-coil tetramerization domain, we
      have engineered a set of buried nonpolar side chains at the a-, d-, and e
      positions into the hydrophobic interior of the dimeric GCN4 leucine zipper.
      Circular dichroism and equilibrium ultracentrifugation studies show that this
      core variant (GCN4-pAeLV) forms a stable tetrameric structure with a reversible
      and highly cooperative thermal unfolding transition. The X-ray crystal structure
      at 1.9 A reveals that GCN4-pAeLV is an antiparallel four-stranded coiled coil of
      the lac repressor type in which the a, d, and e side chains associate by means of
      combined knobs-against-knobs and knobs-into-holes packing with a characteristic
      interhelical offset of 0.25 heptad. Comparison of the side chain shape and
      packing in the antiparallel tetramers shows that the burial of alanine residues
      at the e positions between the neighboring helices of GCN4-pAeLV dictates both
      the antiparallel orientation and helix offset. This study fills in a gap in our
      knowledge of the determinants of structural specificity in antiparallel coiled
      coils and improves our understanding of how specific side chain packing forms the
      teritiary structure of a functional protein.

PMID- 18052215
TI  - Ab initio study of surface acid-base reactions. The case of molecular and
      dissociative adsorption of ammonia on the (011) surface of rutile TiO2.
AB  - The interaction of ammonia molecules with Lewis acid centers (Ti4+ metal ions) of
      the (011) surface of rutile TiO2 is investigated by density functional theory in
      order to understand, from first principle, the nature of acid-base reactions on
      solid surfaces. Unlike the rutile (110) surface that contains alternating rows of
      5-fold and 6-fold Ti atoms, all Ti atoms of the (011) surface are 5-fold
      coordinated. This surface has shown considerable activity for numerous chemical
      reactions and is thus an ideal prototype. At 1/2 monolayer coverage, with respect
      to surface Ti atoms, the adsorption energy is found to be equal to 100 kJ mol-1,
      and drops to 58 kJ mol-1 at one monolayer coverage. Analysis of the electronic
      density of states (DOS) revealed information regarding the mode of adsorption. In
      particular, the nitrogen 3a1 and 2a1 orbitals appear to undergo significant
      changes upon adsorption, in agreement with photoelectron spectroscopy studies.
      Dissociative adsorption was also investigated on the same surface. Both NH2(Tis)
      + H(Os) and NH(Tis) + 2H(Os) modes of dissociative adsorption, where s stands for
      surface, are found to be less stable than the molecular (non dissociated)
      adsorption.

PMID- 18052216
TI  - Preparation and tribological behaviors of an amide-containing stratified self
      assembled monolayers on silicon surface.
AB  - An amide-containing stratified self-assembled film is grafted on a silicon
      surface by a simple two-step method. First, N-[3
      (trimethoxylsilyl)propyl]ethylenediamine (DA) molecules are self-assembled on
      silicon surfaces followed by deriving with stearoyl chloride (STC) through a
      surface coupling reaction. The films are characterized by means of contact angle
      measurement, ellipsometry, and attenuated total reflectance Fourier transformed
      infrared (ATR-FTIR) spectra. STC forms an ordered and hydrophobic film over the
      DA layer with a water contact angle of nearly 110 degrees. A microtribological
      study of the films is carried out on an atomic force microscope (AFM), and the
      wear-resistant property is tested on a ball-on-plate tribometer. Compared to the
      films in our previous study, the friction-reducing and load-affording abilities
      of the film are greatly improved. We contribute the improvements to the existence
      of two layers of hydrogen bonds, which can enhance the stability of the film by
      double in-plane cross-linking.

PMID- 18052213
TI  - Galactomutarotase and other galactose-related genes are rapidly induced by
      retinoic acid in human myeloid cells.
AB  - Aldose-1-epimerase (mutarotase) catalyzes the interconversion of alpha and beta
      hexoses, which is essential for normal carbohydrate metabolism and the production
      of complex oligosaccharides. Galactose mutarotase (GALM) has been well
      characterized at the protein level, but information is lacking on the regulation
      of GALM gene expression. We report herein that all-trans-retinoic acid (RA), an
      active metabolite of vitamin A that is known to induce myeloid lineage cell
      differentiation into macrophage-like cells, induces a rapid and robust regulation
      of GALM mRNA expression in human myeloid cells. all-trans-RA at a physiological
      concentration (20 nM), or Am580, a ligand selective for the nuclear retinoid
      receptor RARalpha, increased GALM mRNA in THP-1 cells, with significantly
      increased expression in 2 h, increasing further to an approximately 8-fold
      elevation after 6-40 h (P < 0.005). In contrast, tumor necrosis factor-alpha did
      not increase GALM mRNA expression, although it is capable of inducing cell
      differentiation. RA also increased GALM mRNA in U937 and HL-60 cells. The
      increase in GALM mRNA by RA was blocked by pretreating THP-1 cells with
      actinomycin D but not by cycloheximide. GALM protein and mutarotase activity were
      also increased time dependently in RA-treated THP-1 cells. In addition to GALM,
      several other genes in the biosynthetic pathway of galactosyl-containing complex
      oligosaccharides were more highly expressed in RA-treated THP-1 cells, including
      B4GALT5, ST3GAL3, ST6GALNAC5, and GALNAC4S-6ST. Thus, the results of this study
      identify RA as a significant regulator of GALM and other galactose-related genes
      in myeloid-monocytic cells, which could affect energy utilization and synthesis
      of cell-surface glycoproteins or glycolipids involved in cell motility, adhesion,
      and/or functional properties.

PMID- 18052218
TI  - Model of nanocrystal formation in solution by burst nucleation and diffusional
      growth.
AB  - The phenomenon of burst nucleation in solution, in which a period of apparent
      chemical inactivity is followed by a sudden and explosive growth of nucleated
      particles from a solute species, has been given a widely accepted qualitative
      explanation by LaMer and co-workers. Here, we present a model with the
      assumptions of instantaneous re-thermalization below the critical nucleus size
      and irreversible diffusive growth above the critical size, which for the first
      time formulates LaMer's explanation of burst nucleation in a manner allowing
      quantitative calculations. The behavior of the model at large times, t, is
      derived with the result that the average cluster size, as measured by the number
      of atoms, grows approximately t, while the width of the cluster distribution
      grows approximately (sq root)1. We develop an effective numerical scheme to
      integrate the equations of the model and compare the asymptotic expressions to
      results from numerical simulation. Finally, we discuss the physical effects which
      cause real nucleation processes in solution to deviate from the behavior of the
      model.

PMID- 18052217
TI  - Dynamic control of protein-protein interactions.
AB  - The capability to selectively and reversibly control protein-protein interactions
      in antibody-doped polypyrrole (PPy) was accomplished by changing the voltage
      applied to the polymer. Polypyrrole was doped with sulfate polyanions and
      monoclonal anti-human fibronectin antibodies (alphaFN). The ability to toggle the
      binding and dissociation of fibronectin (FN) to alphaFN-doped polypyrrole was
      demonstrated. Staircase potential electrochemical impedance spectroscopy (SPEIS)
      was performed to characterize the impedance and charge transfer characteristics
      of the alphaFN-doped PPy as a function of applied voltage, frequency, and FN
      concentration. Impedance measurements indicated oxidation of alphaFN-doped PPy
      promoted selective binding of FN to alphaFN antibodies and reduction of the
      polymer films facilitated FN dissociation. Moreover, SPEIS measurements suggested
      that the apparent reversibility of antigen binding to antibody-doped PPy is not
      due to the suppression of hydrophobic binding forces between antibody and
      antigen. Instead, our data indicate that reversible antigen binding to antibody
      doped PPy can be attributed to the minimization of charge in the polymer films
      during oxidation and reduction. Furthermore, alphaFN-doped PPy was utilized to
      collect real-time, dynamic measurements of varying FN concentrations in solution
      by repeatedly binding and releasing FN. Our data demonstrate that antibody-doped
      PPy represents an electrically controllable sensing platform which can be
      exploited to collect rapid, repeated measurements of protein concentrations with
      molecular specificity.

PMID- 18052219
TI  - Characterization of layer-by-layer self-assembled multilayer films of diblock
      copolymer micelles.
AB  - The in situ layer-by-layer (LbL) self-assembly of low Tg diblock copolymer
      micelles onto a flat silica substrate is reported. The copolymers used here were
      a cationic poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2
      (diethylamino)ethyl methacrylate) (50qPDMA-PDEA; 50q refers to a mean degree of
      quaternization of 50 mol % for the PDMA block) and zwitterionic poly(methacrylic
      acid)-block-poly(2-(diethylamino)ethyl methacrylate) (PMAA-PDEA), which has
      anionic character at pH 9. Alternate deposition of micelles formed by these two
      copolymers onto a silica substrate at pH 9 was examined. The in situ LbL buildup
      of the copolymer micelle films was monitored using zeta potential measurements,
      optical reflectometry, and a quartz crystal microbalance with dissipation
      monitoring (QCM-D). For a six layer deposition, complete charge reversal was
      observed after the addition of each layer. The OR data indicated clearly an
      increase in adsorbed mass with each additional micelle layer and suggest that
      some interdiffusion of copolymer chains between layers and/or an increase in the
      film roughness, and hence in the effective surface area of the micellar
      multilayers, must take place as the film is built up. QCM-D data indicated that
      the self-assembled micellar multilayers on a flat silica substrate undergo
      structural changes over a prolonged period. This is attributed to longer-term
      interdiffusion of the copolymer chains between the outer two layers after the
      initial adsorption of each layer is complete. The QCM-D data further suggest that
      the outer adsorbed layers adopt a progressively more extended conformation,
      particularly for the higher numbered layers. The morphology of each successive
      layer was characterized using in situ soft-contact atomic force microscopy, and
      micelle-like surface aggregates are clearly observed within each layer of the
      complex film, suggesting the persistence of aggregate structures throughout the
      multilayer structure.

PMID- 18052220
TI  - Photoinduced degradation of orange II on different iron (hydr)oxides in aqueous
      suspension: rate enhancement on addition of hydrogen peroxide, silver nitrate,
      and sodium fluoride.
AB  - Photoinduced organic oxidation with iron (hydr)oxides in aqueous suspension has
      been argued with respect to two principal mechanisms: (a) photoinduced ligand-to
      metal charge transfer within a surface complex and (b) semiconductor
      photocatalysis. In this work, the photodegradation of azo dye orange II with UV
      light (lambda > or = 320 nm) in the aerated aqueous suspensions of haematite,
      maghemite, magnetite, goethite, lepidocrocite, and feroxyhite at an initial pH of
      6.5 has been examined. The results showed that (1) all of the catalysts were
      effective at initiating dye photodegradation but the iron oxides appeared to be
      more active than the iron hydroxides; (2) the photodissolution of different iron
      phases and the dye photolysis in the dissolved iron solutions were very slow; (3)
      the initial rate of dye loss was proportional to the initial amount of
      adsorption, implying dye photodegradation on the catalyst surface; and (4) upon
      addition of H2O2, AgNO3, and NaF to the suspension, the rate of dye
      photodegradation was significantly enhanced with all the catalysts. In the
      presence of H2O2, less than 50% of the total rate enhancement was ascribed to the
      photo-Fenton reaction in solution and the dark Fenton reactions in solution and
      on the catalyst. In the presence of AgNO3, about 1 mole of silver particles was
      produced by consuming 3 moles of the dye substrate. In the presence of NaF,
      hydroxyl radicals were detected by an ethanol scavenger, whereas such radicals
      were not found in the absence of NaF. Moreover, under visible-light irradiation
      (lambda > or = 450 nm), the dye degradation was much slower than that under UV
      irradiation, but the reaction was also accelerated by the addition of NaF and
      AgNO3. The results suggest that mechanism b, not mechanism a, is operative for
      dye photodegradation occurring on the iron (hydr)oxides. A detailed discussion of
      all possible pathways is given in the text.

PMID- 18052221
TI  - Nonsolvents cause swelling at the interface with poly(methyl methacrylate) films.
AB  - Density profiles of a perdeuterated poly(methyl methacrylate) (dPMMA) film spin
      coated on a substrate in water, hexane, and methanol, which are "nonsolvents" for
      dPMMA, were examined along the direction normal to the interface by specular
      neutron reflectivity (NR). The interfaces of dPMMA with the liquids were diffuse
      in comparison with the pristine interface with air; the interfacial width with
      water was thicker than that with hexane. Interestingly, in water, the dPMMA film
      was composed of a swollen layer and the interior region, which also contained
      water, in addition to the diffused layer. The interface of dPMMA with hexane was
      sharper than that with water. Although there were slight indications of a swollen
      layer for the dPMMA in hexane, the solvent molecules did not penetrate
      significantly into the film. On the other hand, in methanol, the whole region of
      the dPMMA film was strikingly swollen. To conserve mass, the swelling of the film
      by the nonsolvents is accompanied by an increase in the film thickness. The
      change in the film thickness estimated by NR was in excellent accord with the
      results of direct observations using atomic force microscopy (AFM). The modulus
      of dPMMA in the vicinity of the interfaces with liquids was also examined on the
      basis of force-distance curves measured by AFM. The modulus decreased closer to
      the outermost region of the film. The extent to which the modulus decreased in
      the interfacial region was consistent with the amount of liquid sorbed into the
      film.

PMID- 18052222
TI  - Microporous structure and drug release kinetics of polymeric nanoparticles.
AB  - The aim of the present study was to characterize pegylated nanoparticles (NPs)
      for their microporosity and study the effect of microporosity on drug release
      kinetics. Blank and drug-loaded NPs were prepared from three different pegylated
      polymers, namely, poly(ethylene glycol)1%-graft-poly(D,L)-lactide, poly(ethylene
      glycol)5%-graft-poly(D,L)-lactide, and the multiblock copolymer (poly(D,L)
      lactide-block-poly(ethylene glycol)-block-poly(D,L)-lactide)n. These NPs were
      characterized for their microporosity using nitrogen adsorption isotherms. NPs of
      the multiblock copolymer showed the least microporosity and Brunauer-Emmett
      Teller (BET) surface area, and that of PEG1%-g-PLA showed the maximum. Based on
      these results, the structural organization of poly(D,L)-lactide (PLA) and
      poly(ethylene glycol) (PEG) chains inside the NPs was proposed and was validated
      with differential scanning calorimetry (DSC) and X-ray photoelectron spectroscopy
      (XPS) surface analysis. An in vitro drug release study revealed that PEG1%-g-PLA
      NPs exhibited slower release despite their higher surface area and microporosity.
      This was attributed to the presence of increased microporosity forming tortuous
      internal structures, thereby hindering drug diffusion from the matrix. Thus, it
      was concluded that the microporous structure of NPs, which is affected by the
      molecular architecture of polymers, determines the release rate of the
      encapsulated drug.

PMID- 18052223
TI  - Ionic liquid crystals based on mesitylene-containing bis- and trisimidazolium
      salts.
AB  - The synthesis of novel ionic liquid crystals (ILCs) based on bis- and
      trisimidazolium salts (I-, BF4-, and [N(SO2CF3)2]-) bearing hydrophobic hexadecyl
      chains and a bridging mesitylene moiety is reported. The study of their
      mesomorphic properties is presented, including the characterization of the
      Smectic A phase by differential scanning calorimetry and polarized optical
      microscopy. A detailed powder X-ray diffraction (p-XRD) study as a function of
      temperature confirmed that cooling gives rise to a glass transition from the
      liquid-crystalline smectic A phase to a metastable lamellar phase. In addition,
      in the case of bisimidazolium iodide, the ability of these molecules to form self
      aggregates in solution has been demonstrated by diffusion nuclear magnetic
      resonance (NMR) experiments.

PMID- 18052224
TI  - Micromechanics and contact forces of colloidal aggregates in the presence of
      surfactants.
AB  - We report measurements of the bending mechanics of colloidal aggregates
      consisting of poly(methyl methacrylate) (PMMA) flocculated with 250 mM MgCl2 in
      the presence of either pentaethylene glycol monododecyl ether (C(12)E(5)), a
      nonionic surfactant, or sodium dodecyl sulfate (SDS), an anionic surfactant. In
      the absence of surfactant, singly bonded aggregates exhibit a substantial bond
      rigidity, kappa(0), in the linear bending regime. With the addition of
      surfactant, the tangential restoring force between particles becomes weaker;
      aggregates exhibit nonlinear mechanics at a lower critical bending moment, M(c),
      and the bond rigidity decreases. The decrease in kappa(0) is related to the
      reduction of the surface energy of adhesion between particles, W(SL). We find
      that W(SL) decreases with increasing surfactant concentration below the critical
      micelle concentration (cmc). However, above the cmc, W(SL) remains constant
      within experimental error. These results confirm the relation between the bond
      rigidity and the surface energy of adhesion and clearly demonstrate that, on the
      basis of this relationship, surface-active agents provide a means of tuning the
      macroscopic elasticity and yield stress of colloidal gels. Last, the mechanics of
      the critical moment is consistent with the surfactant lowering the stress at
      which the contact line between the particles de-pins.

PMID- 18052225
TI  - The effect of surface ions on water adsorption to mica.
AB  - We have measured the adsorption isotherms of water on a single surface of freshly
      cleaved mica with K+ on the surface, and on mica where the K+ has been exchanged
      for H+. Using a very sensitive interferometric technique, we have found a
      significant difference between the two isotherms at submonolayer coverage, for
      relative vapor pressures p/p0 < 0.5. The K+-mica isotherm shows a pronounced
      convexity, suggesting distinct adsorption sites, whereas the H+-mica isotherm is
      flatter. The two isotherms converge above monolayer coverage. The results give a
      graphic demonstration of the importance of nanoscale surface heterogeneities for
      vapor adsorption at submonolayer coverage.

PMID- 18052226
TI  - Gallium(III)/4-(2-pyridylazo)resorcinol system in water and SDS solution:
      kinetics and thermodynamics.
AB  - The equilibria and kinetics of the complex formation and dissociation reaction
      between gallium(III) and PAR [4-(2-pyridylazo)resorcinol] have been investigated
      in water and in the presence of SDS micelles. The reactive form of Ga(III) is
      GaOH2+ in both cases. The addition of SDS results in an increase of both the
      binding affinity and velocity, the maximum accelerating effect being observed
      just above the cmc value of SDS that, under the conditions of the experiments, is
      5.6 x 10-3 M. At pH = 3.2, the maximum value of the equilibrium constant ratio
      Kapp(SDS)/Kapp(H2O) is 27.4, whereas that of the binding rate constants
      kf(SDS)/kf(H2O) is 16. The results are interpreted in terms of increased
      concentrations of the reactants on the micelle surface and on competition of PAR
      and SDS for GaOH2+.

PMID- 18052227
TI  - Interactions between adsorbed layers of cationic gemini surfactants.
AB  - The forces acting between glass and between mica surfaces in the presence of two
      cationic gemini surfactants, 1,4 diDDAB (1,4-butyl-bis(dimethyldodecylammonium
      bromide)) and 1,12 diDDAB (1,12-dodecyl-bis(dimethyldodecylammonium bromide)),
      have been investigated below the critical micelle concentration (cmc) of the
      surfactants using two different surface force techniques. In both cases, it was
      found that a recharging of the surfaces occurred at a surfactant concentration of
      about 0.1 x cmc, and at all surfactant concentrations investigated repulsive
      double-layer forces dominated the interaction at large separations. At smaller
      separations, attractive forces, or regions of separation with (close to) constant
      force, were observed. This was interpreted as being due to desorption and
      rearrangement in the adsorbed layer induced by the proximity of a second surface.
      Analysis of the decay length of the repulsive double-layer force showed that the
      majority of the gemini surfactants were fully dissociated. However, the degree of
      ion pair formation, between a gemini surfactant and a bromide counterion,
      increased with increasing surfactant concentration and was larger for the gemini
      surfactant with a shorter spacer length.

PMID- 18052228
TI  - Surface plasmon mediated interference phenomena in low-q silver nanowire
      cavities.
AB  - Optical excitation of surface plasmons in wet-chemically grown monocrystalline
      silver nanowires ( approximately 100 nm diameter and up to a few tens of
      micrometers length) is studied by broadband imaging spectroscopy. Surface
      plasmons excited by an incident light beam in the so-called Kretschmann-Raether
      configuration give optical interference phenomena in the spectral domain. These
      spectral oscillations are interpreted in terms of Fabry-Perot cavity modes for
      surface plasmons in silver nanowires and allow for a direct experimental
      determination of the surface plasmon group velocity and cavity losses.

PMID- 18052229
TI  - Role of molecular surface passivation in electrical transport properties of InAs
      nanowires.
AB  - The existence of large densities of surface states on InAs pins the surface Fermi
      level above the conduction band and also degrades the electron mobility in thin
      films and nanowires. Field effect transistors have been fabricated and
      characterized in the "as fabricated" state and after surface passivation with 1
      octadecanethiol (ODT). Electrical characterization of the transistors shows that
      the subthreshold slope and electron mobility in devices passivated with ODT are
      superior to the respective values in unpassivated devices. An X-ray photoelectron
      spectroscopy study of ODT passivated undoped InAs nanowires indicates that sulfur
      from ODT is bonded to In on the InAs nanowires. Simulations using a two
      dimensional device simulator (MEDICI) show that the improvements in device
      performance after ODT passivation can be quantified in terms of a decrease of
      interface trap electron donor states, shifts in fixed interfacial charge, and
      changes in body and surface mobilities.

PMID- 18052230
TI  - Spermidine modulated ribonuclease activity probed by RNA plasmon rulers.
AB  - We extend the scope of nanometer distance measurements based on coupled pairs of
      gold nanoparticles, or plasmon rulers, to individual RNA molecules. These sensors
      were used to monitor the influence of spermidine on the cleavage kinetics of RNA
      by ribonuclease A. Time-resolved cleavage experiments of individual RNA plasmon
      rulers reveal transiently stabilized RNA sub-populations at increased spermidine
      concentrations that indicate spermidine-induced stabilization of weak secondary
      and tertiary structural elements.

PMID- 18052231
TI  - Supramolecular porphyrin polymers in solution and at the solid-liquid interface.
AB  - We have investigated in detail the self-assembly of a chiral porphyrin trimer in
      different solvents and correlated this behavior to the aggregation of the
      molecule at a solid-liquid interface. In n-hexane and cyclohexane, CD
      spectroscopy and dynamic and static light scattering studies showed that the
      porphyrin trimer self-assembles already at micromolar concentrations into long,
      chiral supramolecular polymers, which precipitate as fibers when the solution is
      drop-cast onto a mica surface. In contrast, in chloroform, the compound is
      molecularly dissolved up to concentrations of 0.2 mM and when micromolar
      solutions are drop-cast onto mica, no precipitation of large assemblies occurs.
      Instead, at the moment that the chloroform film becomes subject to spinodal
      dewetting and the porphyrin trimers within this film start to self-assemble,
      extended patterns of equidistant lines of single molecule thick columnar stacks
      are formed.

PMID- 18052232
TI  - Inherently tunable electrostatic assembly of membrane proteins.
AB  - Membrane proteins are a class of nanoscopic entities that control the matter,
      energy, and information transport across cellular boundaries. Electrostatic
      interactions are shown to direct the rapid co-assembly of proteorhodopsin (PR)
      and lipids into long-range crystalline arrays. The roles of inherent charge
      variations on lipid membranes and PR variants with different compositions are
      examined by tuning recombinant PR variants with different extramembrane domain
      sizes and charged amino acid substitutions, lipid membrane compositions, and
      lipid-to-PR stoichiometric ratios. Rational control of this predominantly
      electrostatic assembly for PR crystallization is demonstrated, and the same
      principles should be applicable to the assembly and crystallization of other
      integral membrane proteins.

PMID- 18052233
TI  - Spectral editing of organic mixtures into pure components using NMR spectroscopy
      and ultraviscous solvents.
AB  - A general technique is described that permits the extraction of a complete 1H NMR
      spectrum for components in organosoluble mixtures. The approach should find a
      wide range of applications considering that pure component spectra can be
      generated without the need for physical separation. This technique is especially
      significant for synthetic organic chemistry and the pharmaceutical industry due
      to the potential to isolate a product spectrum even in the presence of
      overlapping starting materials, byproducts, or degradation products. A viscous
      oil-based solvent system that can be temperature-manipulated from essentially a
      solid at one extreme to a freely flowing liquid at the other is employed. The
      system contains no protons and is miscible with common organic solvents. Through
      careful control of the temperature and thus solvent viscosity, the behavior of
      small molecules moves from the positive to the extreme of the negative NOE
      regime. Under such conditions, all protons in a molecule correlate with all other
      protons as propagation by spin diffusion becomes highly efficient, behavior
      normally only observed with rigid macromolecules in conventional solvents.
      Therefore, as long as one proton (or carbon signal in hybrid experiments) is
      resolved for a component in a mixture, the entire proton spectrum for that
      molecule can be cleanly extracted from a 2D NOESY spectrum (or from selective 1D
      NOE-based analogues). Preliminary results are highly encouraging, indicating that
      the approach may be feasible for a wide range of molecules and mixtures; however,
      in practice the exact types of structures, combinations of structures, and range
      of concentrations that can be cleanly extracted will become evident as the
      technique becomes better established.

PMID- 18052234
TI  - Probing the flexibility of the bacterial reaction center: the wild-type protein
      is more rigid than two site-specific mutants.
AB  - Experimental and theoretical studies have stressed the importance of flexibility
      for protein function. However, more local studies of protein dynamics, using
      temperature factors from crystallographic data or elastic models of protein
      mechanics, suggest that active sites are among the most rigid parts of proteins.
      We have used quasielastic neutron scattering to study the native reaction center
      protein from the purple bacterium Rhodobacter sphaeroides, over a temperature
      range of 4-260 K, in parallel with two nonfunctional mutants both carrying the
      mutations L212Glu/L213Asp --> Ala/Ala (one mutant carrying, in addition, the
      M249Ala --> Tyr mutation). The so-called dynamical transition temperature, Td,
      remains the same for the three proteins around 230 K. Below Td the mean square
      displacement, u2, and the dynamical structure factor, S(Q,omega), as measured
      respectively by backscattering and time-of-flight techniques are identical.
      However, we report that above Td, where anharmonicity and diffusive motions take
      place, the native protein is more rigid than the two nonfunctional mutants. The
      higher flexibility of both mutant proteins is demonstrated by either their higher
      u2 values or the notable quasielastic broadening of S(Q,omega) that reveals the
      diffusive nature of the motions involved. Remarkably, we demonstrate here that in
      proteins, point genetic mutations may notably affect the overall protein
      dynamics, and this effect can be quantified by neutron scattering. Our results
      suggest a new direction of investigation for further understanding of the
      relationship between fast dynamics and activity in proteins. Brownian dynamics
      simulations we have carried out are consistent with the neutron experiments,
      suggesting that a rigid core within the native protein is specifically softened
      by distant point mutations. L212Glu, which is systematically conserved in all
      photosynthetic bacteria, seems to be one of the key residues that exerts a
      distant control over the rigidity of the core of the protein.

PMID- 18052236
TI  - Fast characterization of industrial soy protein isolates by direct analysis with
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
AB  - Industrial soy protein isolates (SPIs) due to differences in their processing
      conditions may differ both in composition and in degree of hydrolysis. As a
      result, they display different performance in food production and final food
      properties like consistency and taste. To address this issue, a fast, cheap, and
      simple method for screening and characterization is required. In this article,
      the successful analysis of soy protein isolates, a complex mixture of proteins
      with glycinin and beta-conglycinin as major components, by matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is
      demonstrated. The preparation implements a fast extraction of the proteins from
      the raw SPI either under neutral or reducing conditions. The extracts are
      analyzed subsequently by MALDI-TOF-MS without further purification. Results of
      the two conditions are compared. Finally, different SPIs from different suppliers
      are analyzed and compared concerning their consistency. The method could be
      applied to other plant proteins and mixtures thereof. Since the composition and
      intactness of different subunits play important roles in functional properties of
      soy proteins, rapid methods for fingerprinting of different industrial soy
      protein sources will be valuable tools for successful product formulation.

PMID- 18052235
TI  - Caught in the Act: the 1.5 A resolution crystal structures of the HIV-1 protease
      and the I54V mutant reveal a tetrahedral reaction intermediate.
AB  - HIV-1 protease (PR) is the target for several important antiviral drugs used in
      AIDS therapy. The drugs bind inside the active site cavity of PR where normally
      the viral polyprotein substrate is bound and hydrolyzed. We report two high
      resolution crystal structures of wild-type PR (PRWT) and the multi-drug-resistant
      variant with the I54V mutation (PRI54V) in complex with a peptide at 1.46 and
      1.50 A resolution, respectively. The peptide forms a gem-diol tetrahedral
      reaction intermediate (TI) in the crystal structures. Distinctive interactions
      are observed for the TI binding in the active site cavity of PRWT and PRI54V. The
      mutant PRI54V/TI complex has lost water-mediated hydrogen bond interactions with
      the amides of Ile50 and Ile50' in the flap. Hence, the structures provide insight
      into the mechanism of drug resistance arising from this mutation. The structures
      also illustrate an intermediate state in the hydrolysis reaction. One of the gem
      diol hydroxide groups in the PRWT complex forms a very short (2.3 A) hydrogen
      bond with the outer carboxylate oxygen of Asp25. Quantum chemical calculations
      based on this TI structure are consistent with protonation of the inner
      carboxylate oxygen of Asp25', in contrast to several theoretical studies. These
      TI complexes and quantum calculations are discussed in relation to the chemical
      mechanism of the peptide bond hydrolysis catalyzed by PR.

PMID- 18052237
TI  - Synthesis and characterization of canola oil-stearic acid-based trans-free
      structured lipids for possible margarine application.
AB  - Incorporation of stearic acid into canola oil to produce trans-free structured
      lipid (SL) as a healthy alternative to partially hydrogenated fats for margarine
      formulation was investigated. Response surface methodology was used to study the
      effects of lipozyme RM IM from Rhizomucor miehei and Candida rugosa lipase
      isoform 1 (LIP1) and two acyl donors, stearic acid and ethyl stearate, on the
      incorporation. Lipozyme RM IM and ethyl stearate gave the best result. Gram
      quantities of SLs were synthesized using lipozyme RM IM, and the products were
      compared to SL made by chemical catalysis and fat from commercial margarines.
      After short-path distillation, the products were characterized by GC and RPHPLC
      MS to obtain fatty acid and triacylglycerol profiles, 13C NMR spectrometry for
      regiospecific analysis, X-ray diffraction for crystal forms, and DSC for melting
      profile. Stearic acid was incorporated into canola oil, mainly at the sn-1,3
      positions, for the lipase reaction, and no new trans fatty acids formed. Most SL
      products did not have adequate solid fat content or beta' crystal forms for tub
      margarine, although these may be suitable for light margarine formulation.

PMID- 18052238
TI  - Anti-inflammatory effects of isoflavone powder produced from soybean cake.
AB  - Soybean cake, a byproduct obtained during the processing of soybean oil, has been
      shown to be a rich source of isoflavones. The objectives of this study were to
      use soybean cake as raw material for processing into powder and to evaluate the
      anti-inflammatory activity. Eleven treatments, including powders of
      malonylglucoside, glucoside, acetylglucoside, aglycone, ISO-1, and ISO-2, as well
      as genistein standard, gamma-PGA, control, normal, and PDTC, were used for
      evaluation. A total of 77 mice were each provided daily with tube feeding for 4
      weeks at a dose of 0.3 mL of aqueous solution from each treatment, and
      inflammation was induced with intraperitoneal injection of 1 mg/kg of body weight
      lipopolysaccharide (LPS). Results showed that all of the isoflavone powders and
      genistein standard were effective in inhibiting LPS-induced inflammation,
      lowering leukocyte number in mice blood and reducing production of IL-1beta, IL
      6, NO, and PGE2 in both peritoneal exudate cell supernatant and peritoneal
      exudate fluid. All of the isoflavone treatments failed to retard T cell
      proliferation; however, both ISO-1 and ISO-2 could inhibit B cell proliferation.
      The difference in anti-inflammatory activity was minor between any of the
      isoflavone treatments.

PMID- 18052239
TI  - Smoke-derived taint in wine: effect of postharvest smoke exposure of grapes on
      the chemical composition and sensory characteristics of wine.
AB  - Although smoke exposure has been associated with the development of smoke taint
      in grapes and subsequently in wine, to date there have been no studies that have
      demonstrated a direct link. In this study, postharvest smoke exposure of grapes
      was utilized to demonstrate that smoke significantly influences the chemical
      composition and sensory characteristics of wine and causes an apparent 'smoke
      taint'. Verdelho grapes were exposed to straw-derived smoke for 1 h and then
      fermented according to two different winemaking treatments. Control wines were
      made by fermenting unsmoked grapes. Sensory studies established a perceivable
      difference between smoked and unsmoked wines; smoked wines were described as
      exhibiting 'smoky', 'dirty', 'earthy', 'burnt' and 'smoked meat' characteristics.
      Quantitative analysis, by means of gas chromatography-mass spectrometry,
      identified guaiacol, 4-methylguaiacol, 4-ethylguaiacol, 4-ethylphenol, eugenol,
      and furfural in each of the wines made from smoked grapes. However, these
      compounds were not detected in the unsmoked wines, and their origin is therefore
      attributed to the application of smoke. Increased ethanol concentrations and
      browning were also observed in wines made from grapes exposed to smoke.

PMID- 18052240
TI  - Saskatoon and wild blueberries have higher anthocyanin contents than other
      Manitoba berries.
AB  - Studies have shown that anthocyanins present in berry fruits have some beneficial
      health effects such as reducing age-associated oxidative stress and possessing
      anti-inflammatory properties. Therefore, six Manitoba berries (wild blueberry,
      Saskatoon berry, raspberry, chokecherry, strawberry, and seabuckthorn) were
      studied for their anthocyanin compositions (mg/100 g) on dry weight basis.
      Saskatoon berry and wild blueberry showed a high content of total anthocyanins
      (562.4 and 558.3 mg/100 g, respectively) that were not significantly (P>0.05)
      different from each other. The corresponding values for other berries: raspberry
      (365.2 mg/100 g), chokecherry (177.39 mg/100 g), and strawberry (97.5 mg/100 g)
      were significantly different from each other (P<0.05), and the total anthocyanin
      content of seabuckthorn was negligible (0.84 mg/100 g). Fifteen major
      anthocyanins were isolated from Manitoba berries. Saskatoon berry and wild
      blueberry contained higher amounts of delphinidin 3-glucoside (Dp-3-glc),
      malvidin 3-glucoside (Mv-3-glc), and malvidin 3-galactoside (Mv-3-gal). Dp-3-glc
      was 263.8 (mg/100 g) in Saskatoon berry and 84.4 (mg/100 g) in wild blueberry,
      whereas the corresponding values for Mv-3-glc in these berries were 47.4 and
      139.6 (mg/100 g), respectively. Raspberry, strawberry, and chokecherry contained
      higher amounts of cyanidin 3-glucoside (Cy-3-glc), cyanidin 3-rutinoside (Cy-3
      rut), and pelargonidin 3-glucoside (Pg-3-glc). The total anthocyanin content of
      Manitoba fruits followed the order: Saskatoon berry and blueberry (high
      anthocyanin berries), raspberry and chokecherry (medium anthocyanin berries),
      strawberry (low anthocyanin berries), and seabuckthorn (negligible anthocyanin
      berries). This study demonstrated that Saskatoon berries and wild blueberries
      have high potential value for fruit growers as well as the food and nutraceutical
      manufacturers because of their high anthocyanin contents.

PMID- 18052241
TI  - Intestinal absorption of luteolin from peanut hull extract is more efficient than
      that from individual pure luteolin.
AB  - Luteoin is one of the main flavones and the crucial effective component of peanut
      hull extract (PHE). The present paper aims to elucidate the absorption mechanism
      of luteolin and clarify whether its absorption occurs primarily at a specific
      site of the intestine by an in situ single-pass intestinal perfusion (SPIP)
      model. Moreover, the paper investigates the difference in absorption of luteolin
      when it is administered in PHE form and as pure luteolin by the SPIP model and in
      vivo pharmacokinetics studies. Results showed that the effective permeability ( P
      eff) and absorption rate constant ( k a) of pure luteolin(5.0 microg/mL) in
      duodenum and jejunum were not significantly different, but markedly higher than
      that in the colon and ileum. The P eff and k a of luteolin in jejunum were
      concentration-independent, and the ATP inhibitor (DNP) did not influence P eff
      and k a of pure luteolin. However, the P eff and k a of luteolin in PHE were
      significantly greater than that of pure luteolin. The pharmacokinetics study
      showed that following oral administration of a single dose of pure luteolin (14.3
      mg/kg) or PHE (= 14.3 mg/kg of luteolin) in rats, the peak concentration of
      luteolin in plasma ( C max) and the area under the concentration curve (AUC) for
      pure luteolin were 1.97 +/- 0.15 microg/mL and 10.7 +/- 2.2 microg/mL.h,
      respectively. These parameters were significantly lower than those of the PHE
      group ( P < 0.05), C max = 8.34 +/- 0.98 microg/mL and AUC = 20.3 +/- 1.3
      microg/mL.h, respectively. It can be concluded that luteolin is absorbed
      passively in the intestine of rats and that its absorption is more efficient in
      the jejunum and duodenum than in the colon and ileum. The bioavailability of
      luteolin in PHE form is significantly greater than that of pure luteolin.

PMID- 18052242
TI  - Convenient large-scale purification of yessotoxin from Protoceratium reticulatum
      culture and isolation of a novel furanoyessotoxin.
AB  - Yessotoxins from a large-scale culture (226 L) of Protoceratium reticulatum
      strain CAWD129 were harvested by filtration followed by solid-phase extraction.
      The extract was purified by column chromatography over basic alumina and reverse
      phase flash chromatography to afford pure yessotoxin (193 mg). Isolation of
      yessotoxin was greatly facilitated by selection of a strain which did not produce
      analogues that interfered with yessotoxin isolation. In addition to yessotoxin,
      numerous minor yessotoxins were detected by LC-MS in other fractions. From one of
      these, an early eluting minor analogue with the same molecular weight as
      yessotoxin and a similar mass spectrometric fragmentation pattern was isolated.
      This analogue was identified by NMR and mass spectrometry as a novel yessotoxin
      analogue containing a furan ring in the side chain. This finding reveals
      biosynthetic flexibility of the yessotoxin pathway in P. reticulatum and confirms
      earlier findings of production of many minor yessotoxin analogues by this alga.
      Production of these analogues appeared to be a constitutive trait of P.
      reticulatum CAWD129.

PMID- 18052243
TI  - Structural determination of hypnosin, a spore germination inhibitor of
      phytopathogenic Streptomyces sp. causing root tumor in melon (Cucumis sp.).
AB  - The structure of a germination inhibitor, hypnosin, isolated from phytopathogenic
      Streptomyces sp. causing root tumor of melon was determined to be 3
      acetylaminopyrazine-2-carboxylic acid (1) by mass spectrometry, computational
      chemical prediction of UV spectrum, and synthesis of candidates. The structure
      activity relationship of hypnosin and anthranilic acid was examined, and it was
      concluded that pyrazinecarboxylic acid or pyridine-2-carboxylic acid was the
      fundamental structure with activity, that methylation of the carboxyl group or
      decarboxylation destroyed activity, and that the presence of an amino group was
      inhibitory to the activity, whereas acetylation or deletion of an amino group
      enhanced activity. Hypnosin inhibited spore germination of some Streptomyces spp.
      in addition to the species with which it was isolated.

PMID- 18052244
TI  - Toward more reliable 13C and 1H chemical shift prediction: a systematic
      comparison of neural-network and least-squares regression based approaches.
AB  - The efficacy of neural network (NN) and partial least-squares (PLS) methods is
      compared for the prediction of NMR chemical shifts for both 1H and 13C nuclei
      using very large databases containing millions of chemical shifts. The chemical
      structure description scheme used in this work is based on individual atoms
      rather than functional groups. The performances of each of the methods were
      optimized in a systematic manner described in this work. Both of the methods,
      least-squares and neural network analyses, produce results of a very similar
      quality, but the least-squares algorithm is approximately 2--3 times faster.

PMID- 18052245
TI  - Synthesis and structural characterization of a new vapochromic Pt(II) complex
      based on the 1-terpyridyl-2,3,4,5,6-pentaphenylbenzene (TPPPB) ligand.
AB  - A novel terpyridine ligand containing a pentaphenylphenyl moiety linked to the
      terpyridyl core (1-terpyridyl-2,3,4,5,6-pentaphenyl-benzene (TPPPB)) has been
      synthesized in good yield and reacted with Pt(DMSO)2Cl2, to produce the cationic
      complex [Pt(TPPPB)Cl]Cl (5). 5 was studied structurally and spectroscopically. It
      is observed to be brightly luminescent in the solid state at room temperature and
      at 77 K, with no change in lambdaem(max). The complex exhibits reversible
      vapochromic behavior upon exposure to methylene chloride vapors, changing color
      from red (5-R) to green (5-G). The shift to higher energy in the emission maximum
      from 654 to 514 nm is the largest vapochromic shift (140 nm) yet reported. The
      [Pt(TPPPB)Cl]Cl complex exhibits high selectivity for certain volatile organic
      compounds (VOCs) including methylene chloride, ethanol, ethyl acetate, and
      acetonitrile. The crystal structures of both the green and red forms have been
      determined by single-crystal X-ray diffraction. In both forms, the cationic
      Pt(II) complex possesses the anticipated square-planar coordination geometry that
      is distorted as a consequence of constraints from the terpyridyl binding.
      Analysis of the crystal packing of the green form (5-G) reveals the presence of
      non-interacting Pt...Pt separations with distances of 3.9092(9) and 4.5483(11) A
      and a zigzag arrangement between neighboring Pt(II) ions. The red form (5-R)
      contains complexes that are stacked with Pt...Pt separations of 3.2981(14) and
      3.3427(14) A, indicative of metallophilic interaction. The change in the emitting
      state, as a consequence of the effect of the volatile organic compounds, results
      from a disruption of the d8-d8 metallophilic interactions in the red form and its
      metal-metal-to-ligand charge transfer (MMLCT) excited state to a more-localized
      Pt(dpi)-to-tpy(pi*) metal-to-ligand charge transfer (MLCT) excited state in the
      green form.

PMID- 18052246
TI  - Halogen exchange and scrambling between C-X and M-X' bonds in copper, nickel, and
      cobalt complexes of 6,6'-bis(bromo/chloromethyl)-2,2'-bipyridine. structural,
      electrochemical, and photochemical studies.
AB  - The synthesis, reactivities, spectroscopic, electrochemical, and structural
      studies of copper(I), copper(II), nickel(II), and cobalt(II) complexes of 6,6'
      bis(bromomethyl)-2,2'-bipyridine (bpy-Br2) and 6,6'-bis(chloromethyl)-2,2'
      bipyridine (bpy-Cl2) have been reported. The copper(I) complex [CuI(bpy
      Br2)2](ClO4) (1) has been obtained in two crystallographic modifications, in
      which the coordination geometry of the metal center has the D2d symmetry. The
      reaction between CuCl2.2H2O and bpy-Br2 has been followed spectrophotometrically
      at 45 degrees C over a period of 7 h, and a mechanism for the intramolecular
      halogen exchange and scrambling in the initially formed compound [CuII(bpy
      Br2)Cl2] (5) has been proposed. Depending upon the reaction conditions, several
      halogen-exchanged products, namely [CuII(bpy-Br1.86Cl0.14)(Cl1.89Br0.11)] (2),
      [CuII(bpy-Br1.81Cl0.19)(Cl1.70Br0.30)(H2O)] (3), and [CuII(bpy
      Br0.63Cl1.37)(Cl0.54Br1.46)] (4), have been isolated in crystalline form. The
      reaction between bpy-Cl2 and CuCl2.2H2O provides [CuII(bpy-Cl2)Cl2] (7) and
      [CuII(bpy-Cl2)Cl2(H2O)] (8), whereas CoCl2.6H2O and NiCl2.6H20 on reaction with
      bpy-Br2 under boiling condition produce [CoII(bpy-Br0.5Cl1.5)(ClBr)] (11) and
      [NiII(bpy-Br0.46Cl1.54)(Cl0.73Br1.27)(H2O)] (12), respectively. The X-ray
      structures determined for the 4-coordinate compounds 2, 4, and 7 show flattened
      tetrahedral geometry for the metal center with the D2 symmetry. Both 5-coordinate
      compounds 3 and 12 have square pyramidal geometry, and whereas the nickel(II)
      complex 12 has near-perfect geometry (tau = 0.015), considerable distortion is
      observed for the copper(II) complex 3 (tau = 0.25). Complexes [CuII(bpy-Cl2)Br2]
      (6) and [CuII(bpy-Br2)Br2] under boiling condition undergo photoreduction to
      produce the dimeric copper(I) complexes [{CuI(bpy-Cl1.30Br0.70)(mu-Br)}2](9) and
      [{CuI(bpy-Br2)(mu-Br)}2] (10), respectively. The fact that the photoreduction of
      [CuII(bpy-Cl2)Br2] (6) and [CuII(bpy-Br2)Br2] do not take place in absence of
      light has been established by spectrophotometric measurements. The crystal
      structures of 9 and 10 have been determined. The electrochemical behavior of all
      the copper complexes 1-10 has been studied in acetonitrile and dichloromethane.
      The E1/2 values for the CuI/CuII redox couples show strong solvent dependence and
      for a given system the E1/2 value is more positive in dichloromethane relative to
      that in acetonitrile. For the compounds [CuII(bpy-Br2-xClx)(Cl2-yBry)] (x = 0-2,
      y = 0-2), the E1/2 values become more positive with the increase of y value.

PMID- 18052247
TI  - Cooperative catalysis by tertiary amino-thioureas: mechanism and basis for
      enantioselectivity of ketone cyanosilylation.
AB  - The mechanism of the enantioselective cyanosilylation of ketones catalyzed by
      tertiary amino-thiourea derivatives was investigated using a combination of
      experimental and theoretical methods. The kinetic analysis is consistent with a
      cooperative mechanism in which both the thiourea and the tertiary amine of the
      catalyst are involved productively in the rate-limiting cyanide addition step.
      Density functional theory calculations were used to distinguish between
      mechanisms involving thiourea activation of ketone or of cyanide in the
      enantioselectivity-determining step. The strong correlation obtained between
      experimental and calculated ee's for a range of substrates and catalysts provides
      support for the most favorable calculated transition structures involving amine
      bound HCN adding to thiourea-bound ketone. The calculations suggest that
      enantioselectivity arises from direct interactions between the ketone substrate
      and the amino-acid derived portion of the catalyst. On the basis of this insight,
      more enantioselective catalysts with broader substrate scope were prepared and
      evaluated experimentally.

PMID- 18052248
TI  - Non-enzymatic covalent protein labeling using a reactive tag.
AB  - We describe herein a new method for covalent labeling of proteins using a
      complementary recognition pair of peptide tag and synthetic molecular probe. The
      rapid and specific covalent labeling of a tag-fused protein was achieved by the
      reaction on the tag site with the probe through their selective molecular
      recognition. The advantages of this method involve the facile functional
      modification and the high labeling specificity of the tag-fused protein, which
      are demonstrated in the labeling experiments in various conditions even inside
      cells.

PMID- 18052249
TI  - Spectroscopic and quantum chemical studies on low-spin FeIV=O complexes: Fe-O
      bonding and its contributions to reactivity.
AB  - High-valent FeIV=O species are key intermediates in the catalytic cycles of many
      mononuclear non-heme iron enzymes and have been structurally defined in model
      systems. Variable-temperature magnetic circular dichroism (VT-MCD) spectroscopy
      has been used to evaluate the electronic structures and in particular the Fe-O
      bonds of three FeIV=O (S = 1) model complexes, [FeIV(O)(TMC)(NCMe)]2+,
      [FeIV(O)(TMC)(OC(O)CF3)]+, and [FeIV(O)(N4Py)]2+. These complexes are
      characterized by their strong and covalent Fe-O pi-bonds. The MCD spectra show a
      vibronic progression in the nonbonding --> pi* excited state, providing the Fe-O
      stretching frequency and the Fe-O bond length in this excited state and
      quantifying the pi-contribution to the total Fe-O bond. Correlation of these
      experimental data to reactivity shows that the [FeIV(O)(N4Py)]2+ complex, with
      the highest reactivity toward hydrogen-atom abstraction among the three, has the
      strongest Fe-O pi-bond. Density functional calculations were correlated to the
      data and support the experimental analysis. The strength and covalency of the Fe
      O pi-bond result in high oxygen character in the important frontier molecular
      orbitals (FMOs) for this reaction, the unoccupied beta-spin d(xz/yz) orbitals,
      that activates these for electrophilic attack. An extension to biologically
      relevant FeIV=O (S = 2) enzyme intermediates shows that these can perform
      electrophilic attack reactions along the same mechanistic pathway (pi-FMO
      pathway) with similar reactivity but also have an additional reaction channel
      involving the unoccupied alpha-spin d(z2) orbital (sigma-FMO pathway). These
      studies experimentally probe the FMOs involved in the reactivity of FeIV=O (S =
      1) model complexes resulting in a detailed understanding of the Fe-O bond and its
      contributions to reactivity.

PMID- 18052250
TI  - Structure of the charge separated state P865(+)Q(A)- in the photosynthetic
      reaction centers of Rhodobacter sphaeroides by quantum beat oscillations and high
      field electron paramagnetic resonance: evidence for light-induced Q(A)-
      reorientation.
AB  - The structure of the secondary radical pair, P865(+)Q(A)-, in fully deuterated
      and Zn-substituted reaction centers (RCs) of the purple bacterium Rhodobacter
      sphaeroides R-26 has been determined by high-time resolution and high-field
      electron paramagnetic resonance (EPR). A computer analysis of quantum beat
      oscillations, observed in a two-dimensional Q-band (34 GHz) EPR experiment,
      provides the orientation of the various magnetic tensors of P865(+)Q(A)- with
      respect to a magnetic reference frame. The orientation of the g-tensor of P865(+)
      in an external reference system is adapted from a single-crystal W-band (95 GHz)
      EPR study [Klette, R.; Torring, J. T.; Plato, M.; Mobius, K.; Bonigk, B.; Lubitz,
      W. J. Phys. Chem. 1993, 97, 2015-2020]. Thus, we obtain the three-dimensional
      structure of the charge separated state P865(+)Q(A)- on a nanosecond time scale
      after light-induced charge separation. Comparison with crystallographic data
      reveals that the position of the quinone is essentially the same as that in the X
      ray structure. However, the head group of Q(A)- has undergone a 60 degrees
      rotation in the ring plane relative to its orientation in the crystal structure.
      Analysis suggests that the two different QA conformations are functionally
      relevant states which control the electron-transfer kinetics from Q(A)- to the
      secondary quinone acceptor QB. It appears that the rate-limiting step of this
      reaction is a reorientation of Q(A)- in its binding pocket upon light-induced
      reduction. The new kinetic model accounts for striking observations by Kleinfeld
      et al. who reported that electron transfer from Q(A)- to QB proceeds in RCs
      cooled to cryogenic temperature under illumination but does not proceed in RCs
      cooled in the dark [Kleinfeld, D.; Okamura, M. Y.; Feher, G. Biochemistry 1984,
      23, 5780-5786].

PMID- 18052251
TI  - Root-growth mechanism for single-walled boron nitride nanotubes in laser
      vaporization technique.
AB  - We present a detailed study of the growth mechanism of single-walled boron
      nitride nanotubes synthesized by laser vaporization, which is the unique route
      known to the synthesis of this kind of tube in high quantities. We have performed
      a nanometric chemical and structural characterization by transmission electron
      microscopy (high-resolution mode (HRTEM) and electron energy loss spectroscopy)
      of the synthesis products. Different boron-based compounds and other impurities
      were identified in the raw synthesis products. The results obtained by the TEM
      analysis and from the synthesis parameters (temperature, boron, and nitrogen
      sources) combined with phase diagram analysis to provide identification of the
      fundamental factors determining the nanotube growth mechanism. Our experiments
      strongly support a root-growth model that involves the presence of a droplet of
      boron. This phenomenological model considers the solubility, solidification, and
      segregation phenomena of the elements present in this boron droplet. In this
      model, we distinguish three different steps as a function of the temperature: (1)
      formation of the liquid boron droplet from the decomposition of different boron
      compounds existing in the hexagonal boron nitride target, (2) reaction of these
      boron droplets with nitrogen gas present in the vaporization chamber and
      recombination of these elements to form boron nitride, and (3) incorporation of
      the nitrogen atoms at the root of the boron particle at active reacting sites
      that achieves the growth of the tube.

PMID- 18052252
TI  - Ligand-specific temperature-dependent shifts in EC50 values for the GABAA
      receptor.
AB  - We introduce a system for temperature control of a commercial microfluidic
      superfusion device that, in combination with patch-clamp, enables rapid
      acquisition of dose-response data at different temperatures. We obtained dose
      response curves for the GABAA receptor, a ligand-gated ion channel, for two
      different agonists at temperatures between 25 and 40 degrees C. For GABA, the
      dose-response curves shifted toward higher EC50 values as the temperature
      increased, whereas for beta-alanine, the EC50 values were constant. This shows
      that temperature is an important factor for obtaining accurate estimations of
      EC50 values and also that such temperature effects can be ligand-specific. Using
      the EC50 values, we estimated the enthalpy of dissociation between the ligand and
      the receptor. Furthermore, the technology introduced here is generally applicable
      to all patch-clamp studies where temperature control is desirable, e.g., studies
      of kinetics and thermodynamics, drug screening, compliant ADME/Tox testing, and
      in studies of temperature-gated ion channels.

PMID- 18052253
TI  - Transfer-NMR and docking studies identify the binding of the peptide derived from
      activating transcription factor 4 to protein ubiquitin ligase beta-TrCP.
      Competition STD-NMR with beta-catenin.
AB  - ATF4 plays a crucial role in the cellular response to stress. The E3 ubiquitin
      ligase, SCF beta-TrCP protein responsible for ATF4 degradation by the proteasome,
      binds to ATF4 through a DpSGXXXpS phosphorylation motif, which is similar but not
      identical to the DpSGXXpS motif found in most other substrates of beta-TrCP. NMR
      studies were performed on the free and bound forms of a peptide derived from this
      ATF4 motif that enabled the elucidation of the conformation of the ligand
      complexed to the beta-TrCP protein and its binding mode. Saturation transfer
      difference (STD) NMR allowed the study of competition for binding to beta-TrCP,
      between the phosphorylation motifs of ATF4 and beta-catenin, to characterize the
      ATF4 binding epitope. Docking protocols were performed using the crystal
      structure of the beta-catenin-beta-TrCP complex as a template and NMR results of
      the ATF4-beta-TrCP complex. In agreement with the STD results, in order to bind
      to beta-TrCP, the ATF4 DpSGIXXpSXE motif required the association of two
      negatively charged areas, in addition to the hydrophobic interaction in the beta
      TrCP central channel. Docking studies showed that the ATF4 DpSGIXXpSXE motif fits
      the binding pocket of beta-TrCP through an S-turning conformation. The distance
      between the two phosphate groups is 17.8 A, which matched the corresponding
      distance 17.1 A for the other extended DpSGXXpS motif in the beta-TrCP receptor
      model. This study identifies the residues of the beta-TrCP receptor involved in
      ligand recognition. Using a new concept of STD competition experiment, we show
      that ATF4 competes and inhibits binding of beta-catenin to beta-TrCP.

PMID- 18052254
TI  - Oxygen-induced radical intermediates in the nNOS oxygenase domain regulated by L
      arginine, tetrahydrobiopterin, and thiol.
AB  - Fully coupled nitric oxide synthase (NOS) catalyzes formation of nitric oxide
      (NO), l-citrulline, NADP+, and water from l-arginine, NADPH, and oxygen.
      Uncoupled or partially coupled NOS catalyzes the synthesis of reactive oxygen
      species such as superoxide, hydrogen peroxide, and peroxynitrite, depending on
      the availability of cofactor tetrahydrobiopterin (BH4) and l-arginine during
      catalysis. We identified three distinct oxygen-induced radical intermediates in
      the ferrous endothelial NOS oxygenase domain (eNOSox) with or without BH4 and/or
      l-arginine [Berka, V., Wu, G., Yeh, H. C., Palmer, G., and Tsai, A.-L. (2004) J.
      Biol. Chem. 279, 32243-32251]. The effects of BH4 and l-arginine on the oxygen
      induced radical intermediates in the isolated neuronal NOS oxygenase domain
      (nNOSox) have been similarly investigated by single-turnover stopped-flow and
      rapid-freeze quench EPR kinetic measurements in the presence or absence of
      dithiothreitol (DTT). Like for eNOSox, we found different radical intermediates
      in the reaction of ferrous nNOSox with oxygen. (1) nNOSox (without BH4 or l-Arg)
      produces superoxide in the presence or absence of DTT. (2) nNOSox (with BH4 and l
      Arg) yields a typical BH4 radical in a manner independent of DTT. (3) nNOSox
      (with BH4 and without l-Arg) yields a new radical. Without DTT, EPR showed a
      mixture of superoxide and biopterin radicals. With DTT, a new approximately 75 G
      wide radical EPR was observed, different from the radical formed by eNOSox. (4)
      The presence of only l-arginine in nNOSox (without BH4 but with l-Arg) caused
      conversion of approximately 70% of superoxide radical to a novel radical,
      explaining how l-arginine decreases the level of superoxide production in nNOSox
      (without BH4 but with l-Arg). The regulatory role of l-arginine in nNOS is thus
      very different from that in eNOS where substrate was only to decrease the rate of
      formation of superoxide but not the total amount of radical. The role of DTT is
      also different. DTT prevents oxidation of BH4 in both isoforms, but in nNOS, DTT
      also inhibits oxidation of two key cysteines in nNOSox to prevent the loss of
      substrate binding. This new role of thiol found only for nNOS may be significant
      in neurodegenerative diseases.

PMID- 18052255
TI  - Catalysis by the isolated tryptophan tryptophylquinone-containing subunit of
      aromatic amine dehydrogenase is distinct from native enzyme and synthetic model
      compounds and allows further probing of TTQ mechanism.
AB  - Para-substituted benzylamines are poor reactivity probes for structure-reactivity
      studies with TTQ-dependent aromatic amine dehydrogenase (AADH). In this study, we
      combine kinetic isotope effects (KIEs) with structure-reactivity studies to show
      that para-substituted benzylamines are good reactivity probes of TTQ mechanism
      with the isolated TTQ-containing subunit of AADH. Contrary to the TTQ-containing
      subunit of methylamine dehydrogenase (MADH), which is catalytically inactive, the
      small subunit of AADH catalyzes the oxidative deamination of a variety of amine
      substrates. Observed rate constants are second order with respect to substrate
      and inhibitor (phenylhydrazine) concentration. Kinetic studies with para
      substituted benzylamines and their dideuterated counterparts reveal KIEs (>6)
      larger than those observed with native AADH (KIEs approximately unity). This is
      attributed to formation of the benzylamine-derived iminoquinone requiring
      structural rearrangement of the benzyl side chain in the active site of the
      native enzyme. This structural reorganization requires motions from the side
      chains of adjacent residues (which are absent in the isolated small subunit). The
      position of Phealpha97 in particular is responsible for the conformational gating
      (and hence deflated KIEs) observed with para-substituted benzylamines in the
      native enzyme. Hammett plots for the small subunit exhibit a strong correlation
      of structure-reactivity data with electronic substituent effects for para
      substituted benzylamines and phenethylamines, unlike native AADH for which a poor
      correlation is observed. TTQ reduction in the isolated subunit is enhanced by
      electron withdrawing substituents, contrary to structure-reactivity studies
      reported for synthetic TTQ model compounds in which rate constants are enhanced
      by electron donating substituents. We infer that para-substituted benzylamines
      are good reactivity probes of TTQ mechanism with the isolated small subunit. This
      is attributed to the absence of structural rearrangement prior to H-transfer that
      limits the rate of TTQ reduction by para-substituted benzylamines in native
      enzyme.

PMID- 18052256
TI  - Mechanism of inhibition of HIV-1 reverse transcriptase by the novel broad-range
      DNA polymerase inhibitor N-{2-[4-(aminosulfonyl)phenyl]ethyl}-2-(2
      thienyl)acetamide.
AB  - Employing a novel strategy, we have virtually screened a large library of
      compounds to identify novel inhibitors of the reverse transcriptase (RT) of HIV
      1. Fifty-six top scored compounds were tested in vitro, and two of them inhibited
      efficiently the DNA polymerase activity of RT. The most effective compound, N-{2
      [4-(aminosulfonyl)phenyl]ethyl}-2-(2-thienyl)acetamide (NAPETA), inhibited both
      RNA-dependent and DNA-dependent DNA polymerase activities, with apparent IC50
      values of 1.2 and 2.1 microM, respectively. This inhibition was specific to the
      RT-associated polymerase activity and did not affect the RNase H activity. NAPETA
      also inhibited two drug-resistant HIV-1 RT mutants as well as HIV-2 RT and other
      DNA polymerases. Kinetic analysis of RT inhibition indicated that the DNA
      polymerase activity of HIV-1 RT was inhibited in a classic noncompetitive manner
      with respect to dTTP, demonstrating a Ki value of 1.2 microM. In contrast, the
      inhibition with respect to the RNA.DNA template was a mixed linear type with a Ki
      value of 0.12 microM and was not affected by the order in which the
      template.primer and inhibitor were added to the reaction mixture. Gel shift and
      surface plasmon resonance analyses confirmed that NAPETA interfered with the
      formation of the RT.DNA complex (that is crucial for the polymerization activity)
      by reducing the affinity of RT for DNA, accounting at least partially for the
      inhibition. It is likely that NAPETA inhibited RT via a mechanism that is
      different from that of the classic non-nucleoside RT inhibitors used for treating
      AIDS/HIV patients and, thus, may serve as a lead compound for the development of
      novel anti-HIV drugs.

PMID- 18052257
TI  - One-electron oxidation and reduction potentials of nitroxide antioxidants: a
      theoretical study.
AB  - High-level ab initio calculations have been used to determine the oxidation and
      reduction potentials of a large number of nitroxides including derivatives of
      piperidine, pyrrolidine, isoindoline, and azaphenalene, substituted with COOH,
      NH2, NH3+, OCH3, OH, and NO2 groups, with a view to (a) identifying a low-cost
      theoretical procedures for the determination of electrode potentials of
      nitroxides and (b) studying the effect of substituents on these systems. Accurate
      oxidation and reduction potentials to within 40 mV (3.9 kJ mol(-1)) of
      experimental values were found using G3(MP2)-RAD//B3-LYP/6-31G(d) gas-phase
      energies and PCM solvation calculations at the B3-LYP/6-31G(d) level. For larger
      systems, an ONIOM method in which G3(MP2)-RAD calculations for the core are
      combined with lower-cost RMP2/6-311+G(3df,2p) calculations for the full system,
      was able to approximate G3(MP2)-RAD values (to within 1.6 kJ mol(-1)) at a
      fraction of the computational cost. The overall ring structure has more effect on
      the electrode potentials than the inclusion of substituents. Azaphenalene
      derivatives display the lowest oxidation potentials and least negative reduction
      potentials and are thus the most promising target to function as antioxidants in
      biological systems. Piperidine and pyrrolidine derivatives have intermediate
      oxidation potentials but on average pyrrolidine derivatives display more negative
      reduction potentials. Isoindoline derivatives show higher oxidation potentials
      and more negative reduction potentials. Within a ring, the substituents have a
      relatively small effect with electron donating groups such as amino and hydroxy
      groups stabilizing the oxidized species and electron withdrawing groups such as
      carboxy groups stabilizing the reduced species, as expected.

PMID- 18052258
TI  - Superelectrophilic activation of 4-heterocyclohexanones. Implications for polymer
      synthesis. A theoretical study.
AB  - The stability and the reactivity of mono- and diprotonated 4-heterocyclohexanones
      as well as cyclohexanone in triflic acid have been studied at the PBE0/aug-cc
      pvtz//PBE0/6-31+G** level of theory. In all cases the first protonation is an
      exergonic process occurring at a carbonyl oxygen except for 4-piperidone where a
      nitrogen atom is protonated fist. Second protonation is only slightly endergonic
      for all studied molecules except for cyclohexanone where the second protonation
      is very unfavorable thermodynamically. According to calculations, diprotonated 4
      heterocyclohexanones are much more active in the reactions of triflic acid
      mediated polyalkoxyalkylation with aromatic hydrocarbons compared to
      monoprotonated ones. The increase of the reactivity of diprotonated 4
      heterocyclohexanones is due to inductive effect rather than through space
      electrostatic influence as follows from the electronic structure analysis of
      dications. Moreover, the second protonation reduces the possibility of an aldol
      condensation side reaction, reducing the enol electrophilicity rendering
      heterocyclohexanones as promising monomers for superacid mediated
      polyhydroxyalkylation.

PMID- 18052259
TI  - Multiple bonds and excited states from the Hartree-Fock-Heitler-London method.
AB  - The recently proposed Hartree-Fock-Heitler-London, HF-HL, method (Corongiu, G. J.
      Phys. Chem. A 2006, 110, 11584) previously tested for single bond molecules is
      validated by potential energy computations for open and closed shells, single and
      multiple bonds, in ground and excited states of homopolar diatomic molecules of
      the first and second period. The simple HF-HL function, including the
      configurations for 2s/2p near degeneracy and avoiding state crossing, yields
      correct dissociation products, qualitatively correct binding, and accounts for
      non-dynamical correlation. Addition of ionic structures improves the ab initio HF
      HL function and yields about 95% of the experimental binding energies on average.
      Computed excitation energies are also in agreement with laboratory values as
      verified for the 3 Pi u and 3 Zeta g- excited states of the C2 molecule.
      Computation of the remaining dynamical correlation using a semiempirical
      functional yields binding energies with an average deviation of 1.5 kcal/mol from
      laboratory values, and total energies with an average deviation of 0.7 kcal/mol
      from exact nonrelativistic dissociation energies.

PMID- 18052260
TI  - Gas-phase structure of a pi-allyl-palladium complex: efficient infrared
      spectroscopy in a 7 T Fourier transform mass spectrometer.
AB  - The performance of infrared (IR) spectroscopy of gas-phase ions in a commercially
      available 7 T Fourier transform ion cyclotron resonance mass spectrometer has
      been characterized. A pi-allyl-palladium reactive intermediate, [(pi
      allyl)Pd(P(C6H5)3)2]+, involved in the catalytic allylation of amine is studied.
      A solution of this transition metal complex is electrosprayed, and the IR
      multiple photon dissociation (IRMPD) spectrum of the mass-selected ions is
      recorded in two spectral ranges. The fingerprint spectrum (650-1550 cm(-1)) is
      recorded using the Orsay free-electron laser, and the dependence of the IRMPD
      efficiency on laser power and irradiation time is characterized. The DFT
      calculated IR absorption spectrum of the [(pi-allyl)Pd(P(C6H5)3)2]+ complex shows
      good agreement with the experimental spectrum. The pi-interaction between the
      palladium and the allyl moiety is reflected by the assignment of the IRMPD bands,
      and the observed allylic CH2 wagging modes appear to form a sensitive probe for
      the pi-interaction strength in metal-pi-allyl complexes. This spectral assignment
      is further supported by the analysis of the different IRMPD photofragmentation
      patterns observed at different photon energies, which are found to result from
      wavelength-specific photofragmentations. Nine peaks are well-resolved in the
      experimental spectrum, for which the bandwidth (fwhm) is on the order of 15 cm(
      1). Resonances with a calculated IR intensity of 5 km/mol or larger are shown to
      be amenable for IRMPD, indicating an excellent sensitivity of our new
      experimental setup. Finally, the IR spectrum has also been recorded in the CH
      stretching region (2950-3150 cm(-1)) using a tabletop IR optical parametric
      oscillator/amplifier (OPO/OPA) laser source.

PMID- 18052261
TI  - Covalent and ionic nature of the dative bond and account of accurate ammonia
      borane binding enthalpies.
AB  - The inherent difficulty in modeling the energetic character of the B-N dative
      bond has been investigated utilizing density functional theory and ab initio
      methods. The underlying influence of basis set size and functions, thermal
      corrections, and basis set superposition error (BSSE) on the predicted binding
      enthalpy of ammonia borane (H3B-NH3) and four methyl-substituted ammonia
      trimethylboranes ((CH3)3B-N(CH3)nH3-n; n = 0-3) has been evaluated and compared
      with experiment. HF, B3LYP, MPW1K, MP2, QCISD, and QCISD(T) have been utilized
      with a wide range of Pople and correlation-consistent basis sets, totaling 336
      levels of theory. MPW1K, B3LYP, and HF result in less BSSE and converge to
      binding enthalpies with fewer basis functions than post-SCF techniques; however,
      the methods fail to model experimental binding enthalpies and trends accurately,
      producing mean absolute deviations (MADs) of 5.1, 10.8, and 16.3 kcal/mol,
      respectively. Despite slow convergence, MP2, QCISD, and QCISD(T) using the 6
      311++G(3df,2p) basis set reproduce the experimental binding enthalpy trend and
      result in lower MADs of 2.2, 2.6, and 0.5 kcal/mol, respectively, when corrected
      for BSSE and a residual convergence error of ca. 1.3-1.6 kcal/mol. Accuracy of
      the predicted binding enthalpy is linked to correct determination of the bond's
      dative character given by charge-transfer frustration, QCTF = -(Delta QN + Delta
      QB). Frustration gauges the incompleteness of charge transfer between the donor
      and the acceptor. The binding enthalpy across ammonia borane and methylated
      complexes is correlated to its dative character (R2 = 0.91), where a more dative
      bond (less charge-transfer frustration) results in a weaker binding enthalpy.
      However, a balance of electronic and steric factors must be considered to explain
      trends in experimentally reported binding enthalpies. Dative bond descriptors,
      such as bond ionicity and covalency are important in the accurate
      characterization of the dative bond. The B-N dative bond in ammonia borane is 65%
      ionic, moderately strong (-27.5 +/- 0.5 kcal/mol), and structurally flexible on
      the donor side to relieve steric congestion.

PMID- 18052262
TI  - Electronic structure and photoionization and dissociation processes of
      bis(trifluoromethoxy)disulfurylperoxide, CF3OS(O)2OOS(O)2OCF3.
AB  - In this work, we present a complete study of the photoionization and dissociation
      processes for bis(trifluoromethoxy)disulfurylperoxide, CF3OS(O)2OOS(O)2OCF3,
      which was generated by UV photolysis of a mixture of (CF3CO)2O, SO2, and O2 at a
      low temperature. The reaction product was detected and characterized by the
      photoelectron (PE) and photoionization mass spectroscopy (PIMS). For comparison,
      the geometric and electronic structures of CF3S(O)2OS(O)2CF3 (a),
      CF3OS(O)2OS(O)2OCF3 (b), and CF3OS(O)2OOS(O)2OCF3 (c) were investigated by the
      combination of experiments and theoretical studies. The PES results show that the
      outer electrons residing in nO(S=O) of b and c are more tightly bound than those
      of a. It is worthwhile mentioning that drastic changes occur in the geometry of c
      after one-electron ionization. The neutral molecule exhibits a gauche structure
      with the SOOS dihedral angle of 124.4 degrees . The first ionization process
      happens on the O-O antibonding orbital. The remarkable geometric changes between
      the ground-state molecule and cation are computed to be the gauche-to-trans
      rotation of deltaSOOS and the prolongation of the S1-O1 single bond length.
      According to the calculated bond dissociation energies, the dissociation process
      was discussed. The calculated results indicate that once the parent ion is
      formed, the dissociation of the S1-O1 bond to form CF3OSO2+ is inevitable.

PMID- 18052263
TI  - Effect of cooperative hydrogen bonding in azo-hydrazone tautomerism of azo dyes.
AB  - Azo-hydrazone tautomerism in azo dyes has been modeled by using density
      functional theory (DFT) at the B3LYP/6-31+G(d,p) level of theory. The most stable
      tautomer was determined both for model compounds and for azo dyes Acid Orange 7
      and Solvent Yellow 14. The effects of the sulfonate group substitution and the
      replacement of the phenyl group with naphthyl on the tautomer stability and on
      the behavior in solvent have been discussed. Intramolecular hydrogen bond
      energies have been estimated for the azo and hydrazone tautomers to derive a
      relationship between the tautomer stability and the hydrogen bond strength. The
      transition structures for proton transfer displayed resonance assisted strong
      hydrogen bonding properties within the framework of the electrostatic-covalent
      hydrogen bond model (ECHBM). Evolution of the intramolecular hydrogen bond with
      changing structural and environmental factors during the tautomeric conversion
      process has been studied extensively by means of the atoms-in-molecules (AIM)
      analysis of the electron density. The bulk solvent effect was examined using the
      self-consistent reaction field model. Special solute-solvent interactions were
      further investigated by means of quantum mechanical calculations after defining
      the first-solvation shell by molecular dynamics simulations. The effect of
      cooperative hydrogen bonding with solvent molecules on the tautomer stability has
      been discussed.

PMID- 18052264
TI  - Modeling metal cation-phosphate interactions in nucleic acids in the gas phase
      via alkali metal cation-triethyl phosphate complexes.
AB  - Threshold collision-induced dissociation techniques are employed to determine the
      bond dissociation energies (BDEs) of complexes of alkali metal cations, Na+, K+,
      Rb+, and Cs+, to triethyl phosphate (TEP). The primary and lowest energy
      dissociation pathway in all cases is the endothermic loss of the neutral TEP
      ligand. Theoretical electronic structure calculations at the B3LYP/6
      311+G(2d,2p)//B3LYP/6-31G* level of theory are used to determine the structures,
      molecular parameters, and theoretical estimates for the BDEs of these complexes.
      For the complexes to Rb+ and Cs+, theoretical calculations were performed using
      hybrid basis sets in which the effective core potentials and valence basis sets
      of Hay and Wadt were used to describe the alkali metal cation, while the standard
      basis sets were used for all other atoms. The agreement between theory and
      experiment is excellent for the complexes to Na+ and K+ and is somewhat less
      satisfactory for the complexes to the heavier alkali metal cations, Rb+ and Cs+,
      where effective core potentials were used to describe the cation. The trends in
      the binding energies are examined. The binding of alkali metal cations to
      triethyl phosphate is compared with that to trimethylphosphate.

PMID- 18052265
TI  - pi-H...O hydrogen bonds: multicenter covalent pi-H interaction acts as the proton
      donating system.
AB  - The MP2 method and the Pople-style basis sets 6-311++G(d,p), 6-311++G(2df,2pd),
      and 6-311++G(3df,3pd) were used to perform calculations on H3O+...C2H2 and
      C2H3+...C2H2 complexes and related species. Hydrogen bonds existing for the
      analyzed complexes were investigated as well as related pi-H...O --> pi...H-O and
      pi-H...pi --> pi...H-pi proton-transfer processes. For some of the complexes
      analyzed the multicenter pi-H interaction possessing the properties of a covalent
      bond acts as a proton donor; more generally it is classified as the Lewis acid.
      The quantum theory of "atoms in molecules" (QTAIM) was also applied to deepen the
      nature of these interactions in terms of characteristics of bond critical points.
      The pi-H...O, O-H...pi, and pi-H...pi interactions analyzed here may be
      classified as hydrogen bonds since their characteristics are the same as or at
      least similar to those of typical hydrogen bonds. H...pi interactions are common
      in crystal structures of organic and organometallic compounds. The analyses
      performed here show a continuum of such interactions since there are H...pi
      contacts possessing the characteristics of weak intermolecular interactions on
      the one hand and pi-H multicenter covalent bonds on the other. Ab initio and
      QTAIM results support the latter statements.

PMID- 18052266
TI  - Resonance Raman spectroscopy and quantum-chemical calculations of push-pull
      molecules: 4-hydroxy-4'-nitroazobenzene and its anion.
AB  - The deprotonation of the push-pull molecule 4-hydroxy-4'-nitroazobenzene leads to
      a substantial variation in the charge distribution over the donor and acceptor
      moieties in the D-pi-azo-pi-A system. The extra charge stabilizes the excited
      state, leading to a drastic red shift of ca. 100 nm in the lambda max of the
      electronic transition and consequently causes significant changes in the
      resonance Raman enhancement profiles. In the neutral species the chromophore
      involves several modes, as nu(CN), nu(NN), and nu s(NO2), while in the anion the
      selective enhancement of the nu s(NO2) and nu(CO-) modes indicates a greater
      geometric variation of the NO2 and CO- moieties in the resonant excited
      electronic state. The interpretation of the electronic transitions and the
      vibrational assignment are supported by quantum-mechanical calculations, allowing
      a consistent analysis of the enhancement patterns observed in the resonance Raman
      spectra.

PMID- 18052267
TI  - High-performance organic field-effect transistors: molecular design, device
      fabrication, and physical properties.
AB  - In the past decade, tremendous progress has been made in organic field-effect
      transistors (OFETs). Their real applications require further development of
      device performance. OFETs consist of organic semiconductors, dielectric layers,
      and electrodes. Organic semiconductors play a key role in determining the device
      characteristics. The properties of the organic semiconductors, such as molecular
      structure and packing, as well as molecular energy levels, can be properly
      controlled by molecular design. Therefore, we designed and synthesized a series
      of organic molecules. The synthesized organic semiconductors exhibit excellent
      field-effect properties due to strong intermolecular interactions and proper
      molecular energy levels. Meanwhile, the influence of the device fabrication
      process, organic semiconductor/dielectric layer interface, and organic
      layer/electrode contact on the device performance was investigated. A deep
      understanding of these factors is helpful to improve field-effect properties.
      Furthermore, single-crystal field-effect transistors are highlighted because the
      single-crystal-based FETs can provide an accurate conducting mechanism of organic
      semiconductors and higher device performance as compared with thin film FETs.

PMID- 18052268
TI  - Continuum simulations of acetylcholine consumption by acetylcholinesterase: a
      Poisson-Nernst-Planck approach.
AB  - The Poisson-Nernst-Planck (PNP) equation provides a continuum description of
      electrostatic-driven diffusion and is used here to model the diffusion and
      reaction of acetylcholine (ACh) with acetylcholinesterase (AChE) enzymes. This
      study focuses on the effects of ion and substrate concentrations on the reaction
      rate and rate coefficient. To this end, the PNP equations are numerically solved
      with a hybrid finite element and boundary element method at a wide range of ion
      and substrate concentrations, and the results are compared with the partially
      coupled Smoluchowski-Poisson-Boltzmann model. The reaction rate is found to
      depend strongly on the concentrations of both the substrate and ions; this is
      explained by the competition between the intersubstrate repulsion and the ionic
      screening effects. The reaction rate coefficient is independent of the substrate
      concentration only at very high ion concentrations, whereas at low ion
      concentrations the behavior of the rate depends strongly on the substrate
      concentration. Moreover, at physiological ion concentrations, variations in
      substrate concentration significantly affect the transient behavior of the
      reaction. Our results offer a reliable estimate of reaction rates at various
      conditions and imply that the concentrations of charged substrates must be
      coupled with the electrostatic computation to provide a more realistic
      description of neurotransmission and other electrodiffusion and reaction
      processes.

PMID- 18052269
TI  - An investigation of water dynamics in binary mixtures of water and dimethyl
      sulfoxide.
AB  - The motion of water molecules in mixtures of water and d6-dimethyl sulfoxide
      (DMSO) has been explored through molecular dynamics (MD) simulations using the
      SPC/E water model (J. Chem. Phys. 1987, 91, 6269) and the P2 DMSO model (J. Chem.
      Phys. 1993, 98, 8160). We evaluate the self-intermediate scattering functions,
      FS(Q,t), which are related by a Fourier transform to the incoherent structure
      factors, S(Q,omega), measured in quasielastic neutron scattering (QNS)
      experiments. We compare our results to recent QNS experiments on these mixtures
      reported by Bordallo et al. (J. Chem. Phys. 2004, 121, 12457). In addition to
      comparing the MD data to the experimental signals, which correspond to a
      convolution of S(Q,omega) with a resolution function, we examine the rotational
      and translational components of FS(Q,t) and investigate to what extent simulation
      results for the single-molecule dynamics follow the dynamical models that are
      used in the analysis of the experimental data. We find that the agreement between
      the experimental signal and the MD data is quite good and that the portion of
      FS(Q,t) due to translational dynamics is well represented by the jump-diffusion
      model. The model parameters and their composition dependence are in reasonable
      agreement with experiment, exhibiting similar trends in water mobility with
      composition. Specifically, we find that water motion is less hindered in water
      rich and water-poor mixtures than it is near equimolar composition. We find that
      the extent of coupling between rotational and translational motion contributing
      to FS(Q,t) increases as the equimolar composition of the mixture is approached.
      Thus, the decoupling approximation, which is used to extract information on
      rotational relaxation from QNS spectra at higher momentum transfer (Q) values,
      becomes less accurate than that in water-rich or DMSO-rich mixtures. We also find
      that rotational relaxation deviates quite strongly from the isotropic rotational
      diffusion model. We explore this issue further by investigating the behavior of
      orientational time correlations for different unit vectors and corresponding to
      Legendre polynomials of orders 1-4. We find that the rotational time correlations
      of water molecules behave in a way that is more consistent with the extended jump
      rotation model recently proposed by Laage and Hynes (Science 2006, 311, 832).

PMID- 18052270
TI  - Predicting noncovalent interactions between aromatic biomolecules with London
      dispersion-corrected DFT.
AB  - Within the framework of Kohn-Sham density functional theory, interaction energies
      of hydrogen bonded and pi-pi stacked supramolecular complexes of aromatic
      heterocycles, nucleobase pairs, and complexes of nucleobases with the anti-cancer
      agent ellipticine as well as its derivatives are evaluated. Dispersion-corrected
      atom-centered potentials (DCACPs) are employed together with a generalized
      gradient approximation to the exchange correlation functional. For all systems
      presented, the DCACP calculations are in very good agreement with available post
      Hartree-Fock quantum chemical results. Estimates of 3-body contributions (<15% of
      the respective interaction energy) and deformation energies (5-15% of the
      interaction energy) are given. Based on our results, we predict a strongly bound
      interaction energy profile for the ellipticine intercalation process with a
      stabilization of nearly 40 kcal/mol (deformation energy not taken into account)
      when fully intercalated. The frontier orbitals of the intercalator-nucleobase
      complex and the corresponding non-intercalated nucleobases are investigated and
      show significant changes upon intercalation. The results not only offer some
      insights into the systems investigated but also suggest that DCACPs can serve as
      an effective way to achieve higher accuracy in density functional theory without
      incurring an unaffordable computational overhead, paving ways for more realistic
      studies on biomolecular complexes in the condensed phase.

PMID- 18052271
TI  - Molecular dynamics simulations of ternary membrane mixture: phosphatidylcholine,
      phosphatidic acid, and cholesterol.
AB  - A ternary mixture of 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC), 1-palmitoyl
      2-oleoyl phosphatidic acid (POPA), and cholesterol (CHOL) works effectively for a
      functional conformation of nicotinic acetylcholine receptor (nAChR) that can
      undergo agonist-induced conformation changes, but POPC alone can stabilize only a
      desensitized state of nAChR. To gain insights into the lipid mixture that has
      strong impact to nAChR functions, we performed more than 50 ns all atom molecular
      dynamic (MD) simulations at 303 K on a fully hydrated bilayer consisting of 240
      POPC, 80 POPA, and 80 CHOL (3:1:1). The MD simulation revealed various
      interactions between different types of molecular pairs that ultimately regulated
      lipid organization. The heterogeneous interactions among three different
      constituents resulted in a broad spectrum of lipid properties, including
      extensive distributions of average area per lipid and varied lipid ordering as a
      function of lipid closeness to CHOL. Higher percentage of POPA than POPC had
      close association with CHOL, which coincided with relatively higher ordering of
      POPA molecules in their acyl chains near lipid head groups. Lower fraction of
      gauche dihedrals was also found in the same region of POPA. Although the CHOL
      molecules had the effects on the enhancement of surrounding lipid order,
      relatively low lipid order parameters and high fraction of gauche bonds were
      observed in the ternary mixture. Collectively, these results suggest that the
      dynamical structure of the ternary system could be determinant for a functional
      nAChR.

PMID- 18052273
TI  - Solid-state NMR study of the post-fluorination of (C2.5F)n fluorine-GIC.
AB  - The conversion of (C2.5F)n fluorine-graphite intercalation compounds (GIC) into
      covalent graphite fluoride during a post-treatment in pure F2 gas is studied by
      solid-state NMR. First, a careful characterization of the starting material is
      performed; in particular, for the first time for fluorinated carbons, two
      dimensional 19F--> 13C cross-polarization wide-line separation (CP-WISE)
      experiments were carried out. This completes the classical NMR data such as 19F
      and 13C chemical shifts, quantitative 13C solid echo, and C-F bond length
      measurements, which were estimated by dipolar recoupling using inverse CP MAS.
      The data of the raw (C2.5F)n and of the samples post-fluorinated at 350, 450, and
      550 degrees C were compared to investigate the C-F bonding as a function of the
      treatment temperature. The C-F bonding is discussed taking into account a
      hyperconjugation of the C-F bonds with neighboring unfluorinated carbon atoms.

PMID- 18052274
TI  - Interplay between hydration and electrostatic attraction in ligand binding:
      direct observation of hydration barrier at reverse micellar interface.
AB  - The recognition of a charged biomolecular surface by an oppositely charged ligand
      is governed by electrostatic attraction and surface hydration. In the present
      study, the interplay between electrostatic attraction and hydration at the
      interface of a negatively charged reverse micelle (RM) at different temperatures
      has been addressed. Temperature-dependent solvation dynamics of a probe H33258
      (H258) at the reverse micellar interface explores the nature of hydration at the
      interface. Up to 45 degrees C, the environmental dynamics reported by the
      interface-binding probe H258 becomes progressively faster with increasing
      temperature and follows the Arrhenius model. Above 45 degrees C, the observed
      dynamics slows down with increasing temperature, thus deviating from the
      Arrhenius model. The slower dynamics at higher temperatures is interpreted to be
      due to increasing contributions from the motions of the surfactant head groups,
      indicating the proximity of the probe to the interface at higher temperatures.
      This suggests an increased electrostatic attraction between the ligand and
      interface at higher temperatures and is attributed to the change in hydration.
      Densimetric and acoustic studies, indeed, show a drastic increase in the apparent
      specific adiabatic compressibility of the water molecules present in RMs after 45
      degrees C, revealing the existence of a softer hydration shell at higher
      temperatures. Our study indicates that the hydration layer at a charged interface
      acts both as physical and energetic barrier to electrostatic interactions of
      small ligands at the interface.

PMID- 18052272
TI  - Protecting peroxidase activity of multilayer enzyme-polyion films using outer
      catalase layers.
AB  - Films constructed layer-by-layer on electrodes with architecture
      {protein/hyaluronic acid (HA)}n containing myoglobin (Mb) or horseradish
      peroxidase (HRP) were protected against protein damage by H2O2 by using outer
      catalase layers. Peroxidase activity for substrate oxidation requires activation
      by H2O2, but {protein/HA}n films without outer catalase layers are damaged slowly
      and irreversibly by H2O2. The rate and extent of damage were decreased
      dramatically by adding outer catalase layers to decompose H2O2. Comparative
      studies suggest that protection results from catalase decomposing a fraction of
      the H2O2 as it enters the film, rather than by an in-film diffusion barrier. The
      outer catalase layers controlled the rate of H2O2 entry into inner regions of the
      film, and they biased the system to favor electrocatalytic peroxide reduction
      over enzyme damage. Catalase-protected {protein/HA}n films had an increased
      linear concentration range for H2O2 detection. This approach offers an effective
      way to protect biosensors from damage by H2O2.

PMID- 18052275
TI  - Nanoreactors based on amphiphilic uracilophanes: self-organization and reactivity
      study.
AB  - New amphiphilic pyrimidinic macrocycles (APMs) with two (APM-1) and three (APM-2)
      decyl tails have been synthesized by quaternization of the bridged N. Complex
      examination of the APM-based systems with the help of tensiometry, conductometry,
      dynamic light scattering, and UV and NMR spectroscopy provides evidence for their
      aggregation. Calculations based on surface tension isotherms and on packing
      parameter considerations make it possible to assume a lamellar packing of
      macrocycles when aggregating. Marked differences in the aggregation behavior of
      APM-1 and APM-2 have been found. The additives of polyethylenimine (PEI) exert
      little influence on the critical micelle concentration (cmc) of APM-1, while in
      the APM-2/PEI systems there occurs a pronounced decrease in the cmc and also a
      ca. 2-fold decrease in the surface area per molecule. The APM-based assemblies
      are explored as nanoreactors for the hydrolysis of O-alkyl O-p-nitrophenyl
      (chloromethyl)phosphonates (alkyl = ethyl, hexyl). The kinetic study reveals a
      minor rate effect of the APM-1-based systems. In the APM-2-based systems an
      acceleration of the hydrolysis of both phosphonates occurs as compared to the
      uncatalyzed process. Within the APM-2 --> APM-2/PEI --> APM-2/PEI/La(III) series,
      due to the cooperative contributions of the supramolecular, polymer, and
      homogeneous catalysis, an increase in the catalytic effect is observed from 30
      times to 3 orders of magnitude as compared to that of the basic hydrolysis of the
      substrates.

PMID- 18052276
TI  - Thermal diffusion forced Rayleigh scattering setup optimized for aqueous
      mixtures.
AB  - We developed a thermal diffusion forced Rayleigh scattering (TDFRS) setup
      operating at a writing wavelength of 980 nm, which corresponds to an absorption
      band of water with an absorption coefficient of approximately 0.5 cm(-1).
      Therefore, aqueous mixtures require no dye to convert the light into heat energy.
      Especially for aqueous system with a complex phase behavior such as surfactant
      systems, the addition of a water soluble dye can cause artifacts. The infrared
      TDFRS (IR-TDFRS) setup has been validated for water/ethanol mixtures with water
      weight fractions c = 0.5-0.95 and in a temperature range between T = 15 degrees C
      to T = 35 degrees C. Comparison with literature data shows an excellent
      agreement. The addition of a small amount (c(dye) approximately 10(-6) wt) of
      adsorbing dye at the writing wavelength allows also the investigation of organic
      mixtures. We investigated the three binary mixtures of dodecane, isobutylbenzene,
      and 1,2,3,4-tetrahydronaphthalene at a weight fraction of c = 0.5 at a
      temperature of 25 degrees C and found good agreement with the Soret coefficients,
      which had been obtained in a benchmark test under the same conditions. Therefore,
      the presented setup is suitable for the investigation of the thermal diffusion
      behavior in aqueous and organic mixtures, and in the case of aqueous systems, the
      addition of a dye can be avoided.

PMID- 18052277
TI  - Quantum state-resolved CO2 collisions at the gas-liquid interface: surface
      temperature-dependent scattering dynamics.
AB  - Energy transfer dynamics at the gas-liquid interface are investigated as a
      function of surface temperature both by experimental studies of CO2 +
      perfluorinated polyether (PFPE) and by molecular dynamics simulations of CO2 +
      fluorinated self-assembled monolayers (F-SAMs). Using a normal incident molecular
      beam, the experimental studies probe scattered CO2 internal-state and
      translational distributions with high resolution infrared spectroscopy. At low
      incident energies [Einc = 1.6(1) kcal/mol], CO2 J-state populations and
      transverse Doppler velocity distributions are characteristic of the surface
      temperature (Trot approximately Ttrans approximately TS) over the range from 232
      to 323 K. In contrast, the rotational and translational distributions at high
      incident energies [Einc = 10.6(8) kcal/mol] show evidence for both trapping
      desorption (TD) and impulsive scattering (IS) events. Specifically, the
      populations are surprisingly well-characterized by a sum of Boltzmann
      distributions where the two components include one (TD) that equilibrates with
      the surface (TTD approximately TS) and a second (IS) that is much hotter than the
      surface temperature (TIS > TS). Support for the superthermal, yet Boltzmann,
      nature of the IS channel is provided by molecular dynamics (MD) simulations of
      CO2 + F-SAMs [Einc = 10.6 kcal/mol], which reveal two-temperature distributions,
      sticking probabilities, and angular distributions in near quantitative agreement
      with the experimental PFPE results. Finally, experiments as a function of surface
      temperature reveal an increase in both sticking probability and
      rotational/translational temperature of the IS component. Such a trend is
      consistent with increased surface roughness at higher surface temperature, which
      increases the overall probability of trapping, yet preferentially leads to
      impulsive scattering of more highly internally excited CO2 from the surface.

PMID- 18052278
TI  - Ion pairing as a possible clue for discriminating between sodium and potassium in
      biological and other complex environments.
AB  - For a series of biologically relevant anions, we present free energy changes upon
      replacing potassium with sodium in a contact ion pair. Calculations performed
      using a combination of molecular dynamics simulations and ab initio methods
      demonstrate the ordering of anions in a Hofmeister series. Small anionic groups
      such as carboxylates preferentially pair with sodium, while intermediate cases
      such as chloride or monovalent phosphate exhibit almost no specificity, and large
      anions (e.g., methylsulfonate) prefer potassium over sodium. These results can
      rationalize different behavior of Na+ versus K+ at the surface of hydrated
      proteins, DNA, and reversed micelles.

PMID- 18052279
TI  - The mechanism of MIO-based aminomutases in beta-amino acid biosynthesis.
AB  - Beta-amino acids are widely used building blocks in both natural and synthetic
      compounds. Aromatic beta-amino acids can be biosynthesized directly from
      proteinogenic alpha-amino acids by the action of MIO (4-methylideneimidazole-5
      one)-based aminomutase enzymes. The uncommon cofactor MIO plays a role in both
      ammonia lyases and 2,3-aminomutases; however, the precise mechanism of the
      cofactor has not been resolved. Here we provide evidence that the electrophilic
      cofactor uses covalent catalysis through the substrate amine to direct the
      elimination and subsequent readdition of ammonia. A mechanism-based inhibitor was
      synthesized and the X-ray cocomplex structure was determined to 2.0 A resolution.
      The inhibitor halts the chemistry of the reverse reaction, providing a stable
      complex that establishes the mode of substrate binding and the importance of
      tyrosine 63 in the chemistry. The proposed mechanism is consistent with the
      biochemistry of aminomutases and ammonia lyases and provides strong support for
      an amine-adduct mechanism of catalysis for this enzyme class.

PMID- 18052280
TI  - Observation of an acryloyl-thiamin diphosphate adduct in the first step of
      clavulanic acid biosynthesis.
AB  - The first committed biosynthetic step toward clavulanic acid, the clinically
      important beta-lactamase inhibitor, is catalyzed by the thiamin diphosphate
      (ThDP)-dependent enzyme N2-(2-carboxyethyl)arginine synthase (CEAS). This protein
      carries out a unique reaction among ThDP-dependent processes in which a C-N bond
      is formed, and an electrophilic acryloyl-thiazolium intermediate of ThDP is
      proposed to be involved, unlike the nucleophilic enamine species typically
      generated by this class of enzymes. Here we present evidence for the existence of
      the putative acryloyl adduct and report the unexpected observation of a long
      wavelength chromophore (lambda = 433 nm), which we attribute to this enzyme-bound
      species. Chemical models were synthesized that both confirm its expected
      absorption (lambda = 310-320 nm) and exclude self-condensation and intramolecular
      imine formation with the cofactor as its cause. Circular dichroism experiments
      and others discount charge transfer as a likely explanation for the approximately
      120 nm red shift of the chromophore ( approximately 25 kcal). Examples are well
      known of charged molecules that exhibit significantly red-shifted UV-visible
      spectra compared to their neutral forms as, for example, polyene cations and dyes
      such as indigo and the cyanines. Rhodopsin is the classic biochemical example
      where the protein (opsin)-bound protonated Schiff base of retinal displays a
      remarkable range of red-shifted absorptions modulated by the protein environment.
      Similar tuning of the chromophoric behavior of the enzyme-bound CEAS
      acryloyl.ThDP species may be occurring.

PMID- 18052281
TI  - Isolation of 6,13-dipropylpentacene and its tautomerization.
AB  - 6,13-Dipropyl-5,14-dihydropentacene was aromatized by the combination of the
      formation of pentacene-DDQ adduct and abstraction of DDQ from the pentacene-DDQ
      adduct with 50 equiv of gamma-terpinene to give 6,13-dipropylpentacene cleanly.
      It was stable and isolable. In the presence of a catalytic amount of acid, 6,13
      dipropylpentacene was isomerized to its tautomer.

PMID- 18052282
TI  - Contact chemistry and single-molecule conductance: a comparison of phosphines,
      methyl sulfides, and amines.
AB  - We compare the low bias conductance of a series of alkanes terminated on their
      ends with dimethyl phosphines, methyl sulfides, and amines and find that
      junctions formed with dimethyl phosphine terminated alkanes have the highest
      conductance. We see unambiguous conductance signatures with these link groups,
      indicating that the binding is well-defined and electronically selective. This
      allows a detailed analysis of the single-molecule junction elongation properties
      which correlate well with calculations based on density functional theory.

PMID- 18052284
TI  - Alkane hydroxylation by a nonheme iron catalyst that challenges the heme paradigm
      for oxygenase action.
AB  - A nonheme iron catalyst catalyzed stereoselective oxidation of alkanes with H2O2
      with remarkable efficiency and exhibiting an unprecedented high incorporation of
      water into the oxidized products. The present results challenge the canonical
      description of oxygenases, the standard oxo-hydroxo tautomerism that applies to
      heme systems and serves as a precedent for alternative pathways for the oxidation
      of hydrocarbons at nonheme iron oxygenases.

PMID- 18052283
TI  - Mossbauer studies of the membrane-associated methane monooxygenase from
      Methylococcus capsulatus bath: evidence for a Diiron center.
AB  - Two methane monooxygenase (MMO) systems have been identified in methanotrophic
      bacteria, namely, a soluble or cytoplasmic MMO and a membrane-associated or
      particulate MMO. The active site of the well-characterized soluble MMO contains a
      bis-mu-hydroxo-bridged diiron cluster. X-ray crystallographic studies of the
      particulate enzyme, pMMO, have identified two copper centers on the alpha subunit
      (pmoB) of the alphabetagamma trimer and a site at the interface of the betagamma
      subunits filled by a Zn, apparently from the crystallization buffer. In our
      hands, pMMO preparations containing 1-2 iron atoms per alphabetagamma show the
      highest catalytic activity. We have employed Mossbauer spectroscopy to
      characterize the iron in our preparations. Interestingly, we find in pMMO a
      component with the same spectral properties as the antiferromagnetically coupled
      diiron(III) cluster in the soluble enzyme. In whole cells, we find nearly 1
      diiron center per alphabetagamma of pMMO; in purified enzyme preparations, only
      10% of the sites appear to be occupied. These occupancies correlate well with the
      measured specific activities of purified pMMO and pMMO in whole cells. We suggest
      that it is the "Zn site" that accommodates the diiron center in active pMMO.

PMID- 18052285
TI  - Selective synthesis combined with chemical separation of single-walled carbon
      nanotubes for chirality selection.
AB  - Single-walled carbon nanotubes (SWNTs) are potential materials for future
      nanoelectronics. Since the electronic and optical properties of SWNTs strongly
      depend on tube diameter and chirality, obtaining SWNTs with narrow (n,m)
      chirality distribution by selective growth or chemical separation has been an
      active area of research. Here, we demonstrate that a new, bimetallic FeRu
      catalyst affords SWNT growth with narrow diameter and chirality distribution in
      methane CVD. At 600 degrees C, methane CVD on FeRu catalyst produced
      predominantly (6,5) SWNTs according to UV-vis-NIR absorption and
      photoluminescence excitation/emission (PLE) spectroscopic characterization. At
      850 degrees C, the dominant semiconducting species produced are (8,4), (7,6), and
      (7,5) SWNTs, with much narrower distributions in diameter and chirality than
      materials grown by other catalysts. Further, we show that narrow
      diameter/chirality growth combined with chemical separation by ion exchange
      chromatography (IEC) greatly facilitates achieving single (m,n) SWNT samples, as
      demonstrated by obtaining highly enriched (8,4) SWNTs with near elimination of
      metallic SWNTs existing in the as-grown material.

PMID- 18052286
TI  - Enrichment tags for enhanced-resolution profiling of the polar metabolome.
AB  - The field of metabolomics aims to develop and apply methods to study the full
      complement of endogenous small molecules in biological systems. One of the major
      challenges in metabolomics is obtaining adequate resolution of compounds with
      similar physicochemical properties. The resolution of polar metabolites can be
      exceptionally problematic as these compounds are often poorly retained with
      reverse phase matrices. Here, we describe an advanced chemoselective tagging
      strategy to enrich and profile highly polar metabolites. Metabolite-reactive tags
      were appended with a hydrophobic p-Cl-phenylalanine residue, which conferred
      enhanced retention and resolution upon labeled small-molecules. Notably, the
      increased resolution afforded by hydrophobic tags minimized overlap in tandem
      mass spectrometry profiles for polar metabolites, thereby facilitating their
      structure determination in complex biological samples. Additionally, the chlorine
      atom of the tag permitted the discrimination of tagged metabolites from
      background peaks (i.e., false positives) and the discovery of metabolites that
      possess multiple copies of the same functional group. These studies designate
      chemoselective small-molecule tags as versatile tools for enriching and profiling
      challenging fractions of the metabolome.

PMID- 18052287
TI  - A formal synthesis of the callipeltoside aglycone.
AB  - A synthesis of the macrocyclic core structure of callipeltoside A and a C9 epimer
      has been achieved by applications of chiral vinylzinc or Kishi-Nozaki-Hiyama (K-N
      H) additions, Roskamp homologations, and acylketene or intramolecular K-N-H
      macrolactonizations as key bond-forming steps.

PMID- 18052288
TI  - Triple channel sensing of Pb(II) ions by a simple multiresponsive ferrocene
      receptor having a 1-deazapurine backbone.
AB  - A new redox, chromogenic, and fluorescent chemosensor molecule based on a
      deazapurine ring selectively senses aqueous Pb2+ in acetonitrile over other metal
      ions examined: redox shift (DeltaE1/2 = 0.15 V of the Fe(II)/Fe(III) redox
      couple), the colorless to orange color change, and an emission change of 620
      fold, with an unprecedented detection limit of 2.7 microg L-1. The signal
      transduction occurs via a reversible CHEF with this inherent quenching metal ion.

PMID- 18052289
TI  - Fluorescent chemodosimeter for selective detection of cyanide in water.
AB  - A coumarin-based fluorescent chemodosimeter with a salicylaldehyde functionality
      as a binding site has been developed for selective detection of cyanide anions
      over other anions in water at biological pH.

PMID- 18052290
TI  - The benzil rearrangement reaction: trapping of a hitherto minor product and its
      application to the development of a selective cyanide anion indicator.
AB  - The isolation and characterization of an intermediate from the benzil-cyanide
      reaction is reported. The use of this trapping chemistry to produce a chemical
      indicator for the cyanide anion is described. It relies on the synthesis and
      reaction of a pi-extended analogue of benzil. Addition of tetrabutylammonium
      cyanide to organic solutions of this species, referred to as compound 3 in the
      text, gives rise to a dramatic change in both color and fluorescence properties.

PMID- 18052291
TI  - Axially chiral BINIM and Ni(II)-catalyzed highly enantioselective 1,3-dipolar
      cycloaddition reactions of azomethine ylides and N-arylmaleimides.
AB  - Axially chiral BINIM-Ni(II) complexes are effective catalysts in the asymmetric
      1,3-dipolar cycloaddition reactions of azomethine ylides and N-arylmaleimides to
      give the corresponding adducts in good yields and up to 95% enantiomeric
      excesses.

PMID- 18052292
TI  - Synthesis and chiroptical properties of cryptophanes having C1-symmetry.
AB  - New enantiopure cryptophanes 3-7 having C(1)-symmetry have been synthesized.
      Electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) have
      been used to investigate their chiroptical properties, and the results are
      compared to those obtained for cryptophane-A (1) having D(3)-symmetry. The ECD
      spectra of compounds 3-7 show Cotton effects that differ from those of
      cryptophane-A. However, our results suggest that a confident determination of the
      absolute configuration of the monofunctionalized cryptophanes can be made using
      ECD spectroscopy. Interestingly, we have found that the ECD spectra of
      cryptophanes, especially the (1)L(b) transition, are very sensitive to the nature
      of the solvent. These spectral modifications are essentially due to bulk solvent
      properties rather than the ability of a particular solvent to insert into the
      cavity of cryptophanes. On the other hand, VCD spectra of the monofunctionalized
      cryptophanes have not revealed significant spectral modifications with respect to
      the VCD spectrum of the CHCl(3) at cryptophane-A complex, except for CHCl(3) at 7
      and to a smaller extent for CHCl(3) at 6. These spectral modifications, which
      essentially consist in lower intensities of VCD bands associated with the
      cryptophane backbone, were perfectly reproduced by ab initio calculations
      performed at DFT (B3PW91/6-31G*) level. These results clearly demonstrate that
      VCD measurements associated with DFT calculations allow an easy determination of
      the absolute configuration of cryptophane-A derivatives.

PMID- 18052293
TI  - Chlorination/cyclodehydration of amino alcohols with SOCl2: an old reaction
      revisited.
AB  - A simple, one-pot preparation of cyclic amines via efficient chlorination of
      amino alcohols with use of SOCl(2) has been developed. This approach obviates the
      need for the classical N-protection/O-activation/cyclization/deprotection
      sequence commonly employed for this type of transformation. The reaction pathways
      and the general scope of this method have also been investigated.

PMID- 18052294
TI  - Geometry and energy of substituted phenyl cations.
AB  - The geometry and the energy of a number of substituted phenyl cations have been
      calculated for both spin states at the UB3LYP/6-31G(d) level (o-, m-, p-Me, OMe,
      NH(2), CN, NO(2)) or at the UB3LYP/6-311++G(2d,p) level (o-, m-, p-SiMe(3), SMe).
      The geometric differences were assessed by means of a self-organizing neural
      network. The triplets maintain a regular hexagonal structure that is minimally
      affected by substituents, while in the singlets C1 puckers inward and, when an
      electron-donating group is present, shifts out of the plane. The triplets have
      the character of aromatic radical ions and are strongly stabilized by electron
      donating substituents, independently of the position of the latter. In the case
      of singlets, the effect of substituents on the energy is weaker and depends on
      the position (the largest effect is exerted when the group is in meta). A two
      parameter correlation of all of the triplet energies shows the predominant
      mesomeric effect of the substituents. In the case of singlets, linear
      correlations are obtained only when each position is treated separately and when
      the predominant effect is inductive for the ortho and, less markedly, the para
      position, whereas at the meta position, mesomeric and inductive effects are
      comparable. The ground state is determined to be the singlet for the parent
      cation and for electron-withdrawing substituted ions. With electron-donating
      substituents, the triplet is the ground state for ortho and para derivatives,
      while the two spin states are roughly isoenergetic when the donating group is in
      the meta position. These data allow predicting the reactivity of each cation.

PMID- 18052295
TI  - Deprotonative metalation of five-membered aromatic heterocycles using mixed
      lithium-zinc species.
AB  - Deprotonation of benzoxazole, benzothiazole, benzo[b]thiophene, benzo[b]furan, N
      Boc-protected indole and pyrrole, and N-phenylpyrazole using an in situ mixture
      of ZnCl(2).TMEDA (0.5 equiv) and lithium 2,2,6,6-tetramethylpiperidide (1.5
      equiv) in THF at room temperature is described. The reaction was evidenced by
      trapping with iodine, regioselectively giving the expected functionalized
      derivatives in 52-73% yields. A mixture of mono- and disubstituted derivatives
      was obtained starting from thiazole. Cross-coupling reactions of 2-metalated
      benzo[b]thiophene and benzo[b]furan with heteroaromatic chlorides proved possible
      under palladium catalysis. A reaction pathway where the lithium amide and zinc
      diamide present in solution behave synergically was proposed for the
      deprotonation reaction, taking account of NMR and DFT studies carried out on the
      basic mixture.

PMID- 18052296
TI  - Microwave-mediated nickel-catalyzed cyclotrimerization reactions: total synthesis
      of illudinine.
AB  - Rapid and efficient [2 + 2 + 2] cyclotrimerization reactions were discovered
      through the application of microwave irradiation in conjunction with a
      Ni(CO)(2)(PPh(3))(2) catalyst. This enables the facile construction of highly
      substituted indane, isoindoline, and tetraline core structures. The developed
      microwave-mediated Ni-catalyzed cyclotrimerization reaction was employed as the
      key step in a concise synthesis of the isoquinoline natural product illudinine.
      This represents the first example of a Ni-catalyzed cyclotrimerization reaction
      in total synthesis.

PMID- 18052297
TI  - Rhodium-catalyzed oxidative coupling of triarylmethanols with internal alkynes
      via successive C-H and C-C bond cleavages.
AB  - The rhodium-catalyzed oxidative coupling of triarylmethanols with internal
      alkynes effectively proceeds in a 1:2 manner via cleavage of C-H and C-C bonds to
      produce the corresponding naphthalene derivatives. Addition of tri- or
      tetraphenylcyclopentadiene as a ligand is crucial for the reaction to occur
      efficiently.

PMID- 18052298
TI  - An electrochemical study into the interaction between complement-derived peptides
      and DOPC mono- and bilayers.
AB  - Electrochemical methods employing the hanging mercury drop electrode were used to
      study the interaction between variants of the complement-derived antimicrobial
      peptide CNY21 (CNYITELRRQH ARASHLGLAR) and dioleoyl phosphatidylcholine (DOPC)
      monolayers. Capacitance potential and impedance measurements showed that the
      CNY21 analogues investigated interact with DOPC monolayers coating the mercury
      drop. Increasing the peptide hydrophobicity by substituting the two histidine
      residues with leucine resulted in a deeper peptide penetration into the
      hydrophobic region of the DOPC monolayer, indicated by an increase in the
      dielectric constant of the lipid monolayer (Deltaepsilon = 2.0 after 15 min
      interaction). Increasing the peptide net charge from +3 to +5 by replacing the
      histidines by lysines, on the other hand, arrests the peptide in the lipid head
      group region. Reduction of electroactive ions (Tl+, Pb2+, Cd2+, and Eu3+) at the
      monolayer-coated electrode was employed to further characterize the types of
      defects induced by the peptides. All peptides studied permeabilize the monolayer
      to Tl+ to an appreciable extent, but this effect is more pronounced for the more
      hydrophobic peptide (CNY21L), which also allows penetration of larger ions and
      ions of higher valency. The results for the various ions indicate that charge
      repulsion rather than ion size is the determining factor for cation penetration
      through peptide-induced defects in the DOPC monolayer. The effects obtained for
      monolayers were compared to results obtained with bilayers from liposome leakage
      and circular dichroism studies for unilamellar DOPC vesicles, and in situ
      ellipsometry for supported DOPC bilayers. Trends in peptide-induced liposome
      leakage were similar to peptide effects on electrochemical impedance and
      permeability of electroactive ions for the monolayer system, demonstrating that
      formation of transmembrane pores alone does not constitute the mechanism of
      action for the peptides investigated. Instead, our results point to the
      importance of local packing defects in the lipid membrane in close proximity to
      the adsorbed peptide molecules.

PMID- 18052299
TI  - Gold nanoparticles with perfluorothiolate ligands.
AB  - Two syntheses of gold nanoparticles with fluorinated alkyl and aryl thiolate
      ligands are reported. The fluorous Au nanoparticles are smaller than previous
      gold fluor-capped examples, and are in the 44-75 Au atom size range. Fluoroalkyl
      thiolate-protected (1H,1H,2H,2H-perfluorodecanethiolate) nanoparticles
      synthesized by a Brust reaction are a mixture of (mainly) approximately 8.5 kDa
      (ca. 44 core atoms) and approximately 14 kDa (ca. 75 core atoms) species, by
      MALDI-mass spectrometry. This composition is consistent with thermogravimetric
      analysis (TGA) results of the ligand shell composition. 19F NMR spectra display a
      progressive line broadening of resonances for fluorine sites closer to the Au
      core. A second synthetic route used a (ligand replacement) reaction of
      pentafluorobenzenethiol with Au55(PPh3)12Cl6. The exchange is (as previously
      observed for nonfluorinated thiols) accompanied by nanoparticle core size changes
      to produce a polydisperse mixture within which a Au75 core species could be
      electrochemically discerned by its characteristic 0.74 V electrochemical energy
      gap. Further characterization of the polydisperse nanoparticle product was done
      by HPLC, TEM, TGA, optical spectroscopy, and NMR data. Both varieties of fluorous
      nanoparticles exhibit solubilities typical of perfluorinated materials, as
      opposed to proteo versions.

PMID- 18052300
TI  - Gold nanoparticles enhance the anti-leukemia action of a 6-mercaptopurine
      chemotherapeutic agent.
AB  - 6-mercaptopurine and its riboside derivatives are some of the most widely
      utilized anti-leukemic and anti-inflammatory drugs. Their short biological half
      life and severe side effects limit their use. A new delivery method for these
      drugs based on 4-5 nm gold nanoparticles can potentially resolve these issues. We
      have found substantial enhancement of the antiproliferative effect against K-562
      leukemia cells of Au nanoparticles bearing 6-mercaptopurine-9-beta-d
      ribofuranoside compared to the same drug in typically administered free form. The
      improvement was attributed to enhanced intracellular transport followed by the
      subsequent release in lysosomes. Enhanced activity and nanoparticle carriers will
      make possible the reduction of the overall concentration of the drug, renal
      clearance, and, thus, side effects. The nanoparticles with mercaptopurine also
      showed excellent stability over 1 year without loss of inhibitory activity.

PMID- 18052301
TI  - Experimental verification of an exact evanescent light scattering model for TIRM.
AB  - Total internal reflection microscopy (TIRM) is a method for the precise
      measurement of interaction potentials between a spherical colloidal particle and
      a wall. The method is based on single-particle evanescent wave light scattering.
      The well-established model used to interpret TIRM data is based on an exponential
      relation between scattering intensity and particle wall distance. However,
      applying this model for a certain range of experimental parameters leads to
      significant distortions of the measured potentials. Using a TIRM setup based on a
      two-wavelength illumination technique, we were able to directly measure the
      intensity distance relation revealing deviations from an exponential decay. The
      intensity-distance relations could be compared to scattering simulations taking
      into account exact experimental parameters and multiple reflections between a
      particle and the wall. Converging simulation results were independently obtained
      by the T-matrix method and the discrete sources method (DSM) and show excellent
      agreement with experiments. Using the new scattering model for data evaluation,
      we could reconstruct the correct potential shape for distorted interaction
      potentials as we demonstrate. The comparison of simulations to experiment
      intrinsically yields a new method to determine absolute particle-wall distances,
      a highly desired quantity in TIRM experiments.

PMID- 18052302
TI  - Graphene nanoFlakes with large spin.
AB  - We investigate, using benzenoid graph theory and first-principles calculations,
      the magnetic properties of arbitrarily shaped finite graphene fragments to which
      we refer as graphene nanoflakes (GNFs). We demonstrate that the spin of a GNF
      depends on its shape due to topological frustration of the pi-bonds. For example,
      a zigzag-edged triangular GNF has a nonzero net spin, resembling an artificial
      ferrimagnetic atom, with the spin value scaling with its linear size. In general,
      the principle of topological frustration can be used to introduce large net spin
      and interesting spin distributions in graphene. These results suggest an avenue
      to nanoscale spintronics through the sculpting of graphene fragments.

PMID- 18052303
TI  - It's all a matter of intermolecular forces--a tribute to Giacinto Scoles.

PMID- 18052308
TI  - Partition theory: a very simple illustration.
AB  - We illustrate the main features of a recently proposed method based on ensemble
      density functional theory to divide rigorously a complex molecular system into
      its parts (J. Phys. Chem. A 2007, 111, 2229). The illustrative system is an
      analog of the hydrogen molecule for which analytic expressions for the densities
      of the parts (hydrogen "atoms") are found along with the "partition potential"
      that enters the theory. While previous formulations of chemical reactivity theory
      lead to zero, or undefined, values for the chemical hardness of the isolated
      parts, we demonstrate they can acquire a finite and positive hardness within the
      present formulation.

PMID- 18052309
TI  - Double-trap kinetic equation for the oxygen reduction reaction on Pt(111) in
      acidic media.
AB  - We derived an intrinsic kinetic equation for the four-electron oxygen reduction
      reaction (ORR) in acidic media using free energies of activation and adsorption
      as the kinetic parameters. Our kinetic model consists of four essential
      elementary reactions: a dissociative adsorption (DA) and a reductive adsorption
      (RA), which yield two reaction intermediates, O and OH; a reductive transition
      (RT) from O to OH; and a reductive desorption (RD) of OH. Analytic expressions
      were found for the O and OH adsorption isotherms by solving the steady-state rate
      equations. For the ORR on Pt(111) in 0.1 M HClO4 solution, we analyzed the
      measured polarization curves, thereby deducing activation free energies that are
      consistent with the values from theoretical calculations. The reductive
      adsorption (DeltaG*0RA=0.46 eV) is not the rate-determining step (RDS) for the
      ORR on Pt because dissociative adsorption (DeltaG*0DA=0.26 eV) offers a more
      favorable pathway at high potentials. It, however, generates strongly adsorbed O.
      The high activation barriers for the O to OH transition (DeltaG*0RT=0.50 eV) and
      OH desorption (DeltaG*0RD=0.45 eV) cause a large potential loss for the
      desorption-limited ORR. As the OH coverage increases to a constant value with
      decreasing potential, the Tafel slope increases to the value determined by a
      symmetric electron-transfer coefficient. We discuss the role of adsorption
      isotherm in kinetic analysis and, via activity-and-barrier plots, illustrate why
      the RDS may vary with reaction conditions or may not exist. Recognizing such
      features of electrocatalytic reactions can facilitate reaching the long-standing
      goal of quantitative descriptions and predictions of electrocatalysts'
      activities.

PMID- 18052310
TI  - Structural characterization of aldehyde-terminated self-assembled monolayers.
AB  - The structure of aldehyde-terminated alkanethiol self-assembled monolayers (SAMs)
      on Au(111) is investigated using scanning tunneling microscopy (STM), atomic
      force microscopy (AFM), and density functional theory (DFT) calculations. For the
      first time, the structures of aldehyde-terminated SAMs are revealed with
      molecular resolution. SAMs of 11-mercapto-1-undecanal exhibit the basic
      (radical3xradical3)R30 degrees periodicity and form various c(4x2)
      superstructures upon annealing. In conjunction with DFT studies, the models of
      the (radical3xradical3)R30 degrees and the c(4x2) superstructures are
      constructed. In comparison with alkanethiol SAMs, the introduction of aldehyde
      termini results in smaller domain size, lower degree of long-range order, large
      coverage of disordered areas, and higher density of missing molecules and other
      point defects within domains of closely packed molecules. The origin of these
      structural differences is mainly attributed to the strong dipole-dipole
      interactions among the aldehyde termini.

PMID- 18052311
TI  - Rovibrational energy transfer in the 4nuCH manifold of acetylene, viewed by IR-UV
      double resonance spectroscopy. 5. Detailed kinetic model.
AB  - Time-resolved infrared-ultraviolet double resonance (IR-UV DR) spectroscopy
      provides a distinctive way to examine collision-induced state-to-state energy
      transfer between rotational J-levels in vibrational manifolds of small polyatomic
      molecules, such as acetylene (C2H2) in its electronic ground state X. We consider
      the 4nuCH rovibrational manifold of C2H2 at approximately 12,700 cm(-1), where
      the principal source of IR-brightness is the (nu1+3nu3) or (1 0 3 0 0)0 Sigma+u
      vibrational combination level. In this highly congested manifold, anharmonic, l
      resonance, and Coriolis couplings affect the J-levels of interest, implicating
      them in a complicated variety of intramolecular dynamics. Previous papers of this
      series have reported several seemingly anomalous J-resolved phenomena induced by
      collisions in C2H2 gas at room temperature with pressures and IR-UV pump-probe
      delay intervals corresponding to remarkably high Lennard-Jones collisional
      efficiencies P: odd-DeltaJ rotational energy transfer (10(-3)<P<0.1), in addition
      to regular even-DeltaJ transfer (P approximately 0.3 for typical |DeltaJ|=2
      transfer); particular rovibrational "gateway" channels, such as via (nu1+3nu3)
      Sigma+u J=12 (with P as high as approximately 0.1); an apparently ubiquitous
      collision-induced quasi-continuous background (10(-3)<P<0.1) that accounts for
      much of the observed collision-induced odd-DeltaJ satellite structure. These
      phenomena have been characterized by means of systematic IR-UV DR kinetic
      measurements, with IR pump and UV probe wavelengths and sample pressure fixed
      while the IR-UV pump-probe delay is scanned. In this paper, a detailed master
      equation model is constructed to provide a satisfactory phenomenological fit to
      the IR-UV DR kinetic data, thereby offering mechanistic insight. This model
      includes collision-induced energy transfer between discrete rovibrational levels
      in an IR-bright manifold V and a quasi-continuous bath B, mediated by a J
      specific gateway manifold G.

PMID- 18052312
TI  - High-resolution mapping of the electrostatic potential in organic thin-film
      transistors by phase electrostatic force microscopy.
AB  - We investigate by a scanning probe technique termed phase-electrostatic force
      microscopy the local electrostatic potential and its correlation to the
      morphology of the organic semiconductor layer in operating ultra-thin film
      pentacene field effect transistors. This technique yields a lateral resolution of
      about 60 nm, allowing us to visualize that the voltage drop across the transistor
      channel is step-wise. Spatially localized voltage drops, adding up to about 75%
      of the potential difference between source and drain, are clearly correlated to
      the morphological domain boundaries in the pentacene film. This strongly supports
      and gives a direct evidence that in pentacene ultra-thin film transistors charge
      transport inside the channel is ultimately governed by domain boundaries.

PMID- 18052313
TI  - Crystallographic investigation of the inhibition mode of a VIM-2 metallo-beta
      lactamase from Pseudomonas aeruginosa by a mercaptocarboxylate inhibitor.
AB  - The VIM-2 metallo-beta-lactamase enzyme from Pseudomonas aeruginosa catalyzes the
      hydrolysis of most beta-lactam antibiotics including carbapenems, and there are
      currently no potent inhibitors of such enzymes. We found rac-2-omega-phenylpropyl
      3-mercaptopropionic acid, phenylC3SH, to be a potent inhibitor of VIM-2. The
      structure of the VIM-2-phenylC3SH complex was determined by X-ray crystallography
      to 2.3 A. The structure revealed that the thiol group of phenylC3SH bridged to
      the two zinc(II) ions and the phenyl group interacted with Tyr67(47) on loop1
      near the active site, by pi-pi stacking interactions. The methylene group
      interacted with Phe61(42) located at the bottom of loop1 through CH-pi
      interactions. Dynamic movements were observed in Arg228(185) and Asn233(190) on
      loop2, compared with the native structure (PDB code: 1KO3 ). These results
      suggest that the above-mentioned four residues play important roles in the
      binding and recognition of inhibitors or substrates and in stabilizing a loop in
      the VIM-2 enzyme.

PMID- 18052314
TI  - N-(substituted-anilinoethyl)amides: design, synthesis, and pharmacological
      characterization of a new class of melatonin receptor ligands.
AB  - A novel series of melatonin receptor ligands, characterized by a N-(substituted
      anilinoethyl)amido scaffold, along with preliminary structure-activity
      relationships (SARs), is presented. MT1 and MT2 receptor binding affinity and
      intrinsic activity have been modulated by the introduction of different
      substituents on the aniline nitrogen, on the benzene ring, and on the amide side
      chain. Modulation of intrinsic activity and MT2 selectivity of the newly
      synthesized compounds has been achieved by applying SAR models previously
      developed, providing compounds with different binding and intrinsic activity
      profiles. Compound 3d, with a bulky ss-naphthyl group, behaves as an MT2
      selective antagonist with sub-nM affinity. Size reduction of the substituent
      enhances intrinsic activity, as in the nonselective N-methyl-anilino agonist 3i.
      The phenyl derivative 3g is an MT2-selective partial agonist, with MT2 binding
      affinity higher than melatonin, showing promising sleep-promoting and antianxiety
      properties in animal models.

PMID- 18052315
TI  - Synthesis and in vivo antitumor evaluation of 2-methoxyestradiol 3-phosphate, 17
      phosphate, and 3,17-diphosphate.
AB  - A prodrug strategy was investigated to address the problem of limited aqueous
      solubility and the resulting limited bioavailability of the antitumor agent 2
      methoxyestradiol. The 3-phosphate, 17-phosphate, and 3,17-diphosphate of 2
      methoxyestradiol were synthesized. 2-methoxyestradiol 3-phosphate was metabolized
      more efficiently to the parent compound in vivo than 2-methoxyestradiol 17
      phosphate, and it was also more cytotoxic in cancer cell cultures than either the
      17-phosphate or the 3,17-diphosphate. These results agree with the in vivo
      anticancer activity of 2-methoxyestradiol 3-phosphate in a mouse Lewis lung
      carcinoma experimental metastasis model as opposed to the 17-phosphate and 3,17
      diphosphate, both of which were inactive. The in vivo antitumor activity of 2
      methoxyestradiol 3-phosphate at a dose of 200 mg/kg per day was comparable to
      that of a maximally tolerated dose of cyclophosphamide.

PMID- 18052316
TI  - Syntheses of nicotinamide riboside and derivatives: effective agents for
      increasing nicotinamide adenine dinucleotide concentrations in mammalian cells.
AB  - A new two-step methodology achieves stereoselective synthesis of beta
      nicotinamide riboside and a series of related amide, ester, and acid nucleosides.
      Compounds were prepared through a triacetylated-nicotinate ester nucleoside, via
      coupling of either ethylnicotinate or phenylnicotinate with 1,2,3,5-tetra-O
      acetyl-beta-D-ribofuranose. Nicotinamide riboside, nicotinic acid riboside, O
      ethylnicotinate riboside, O-methylnicotinate riboside, and several N-alkyl
      derivatives increased NAD+ concentrations from 1.2-2.7-fold in several mammalian
      cell lines. These findings establish bioavailability and potent effects of these
      nucleosides in stimulating the increase of NAD+ concentrations in mammalian
      cells.

PMID- 18052317
TI  - Hypoxia-selective 3-alkyl 1,2,4-benzotriazine 1,4-dioxides: the influence of
      hydrogen bond donors on extravascular transport and antitumor activity.
AB  - Tirapazamine (TPZ) and related 1,2,4-benzotriazine 1,4 dioxides (BTOs) are
      selectively toxic under hypoxia, but their ability to kill hypoxic cells in
      tumors is generally limited by their poor extravascular transport. Here we show
      that removing hydrogen bond donors by replacing the 3-NH2 group of TPZ with
      simple alkyl groups increased their tissue diffusion coefficients as measured in
      multicellular layer cultures. This advantage was largely retained using
      solubilizing 3-alkylaminoalkyl substituents provided these were sufficiently
      lipophilic at pH 7.4. The high reduction potentials of such compounds resulted in
      rates of metabolism too high for optimal penetration into hypoxic tissue, but
      electron-donating 6- and 7-substituents moderated metabolism.
      Pharmacokinetic/pharmacodynamic model-guided screening was used to select BTOs
      with optimal extravascular transport and hypoxic cytotoxicity properties for
      evaluation against HT29 human tumor xenografts in combination with radiation.
      This identified four novel 3-alkyl BTOs providing greater clonogenic killing of
      hypoxic cells than TPZ at equivalent host toxicity, with the 6
      morpholinopropyloxy-BTO 22 being 3-fold more active.

PMID- 18052318
TI  - 4-acyl-1-(4-aminoalkoxyphenyl)-2-ketopiperazines as a novel class of non-brain
      penetrant histamine H3 receptor antagonists.
AB  - A series of ketopiperazines were prepared and evaluated for their activity as
      histamine H 3 antagonists. From investigation of the tertiary basic center in the
      aminopropyloxyphenyl template, the 2( R)-methylpyrrolidine was identified as the
      most potent amine. In the more rigid piperidineoxyphenyl template the N
      cyclobutyl group was the most potent amine. The 4-fluorobenzyol, 4-cyanobenzoyl,
      and 2,4-difluorobenzoyl groups provided good pharmacokinetic profiles for the
      various amides. The PSA and log D values of these compounds suggested low brain
      penetration. The compounds had very high selectivity over other receptors and did
      not inhibit hepatic cytochrome P450, indicating low drug-drug interaction
      potential. Compound 22i was identified as the best compound of this series based
      on its overall profile of high potency, selectivity, low brain penetration, lack
      of CYP450 inhibition, high oral bioavailability, and pharmacokinetic properties.

PMID- 18052319
TI  - Dihydro-alkylthio-benzyl-oxopyrimidines as inhibitors of reverse transcriptase:
      synthesis and rationalization of the biological data on both wild-type enzyme and
      relevant clinical mutants.
AB  - A series of novel S-DABO analogues, characterized by different substitution
      patterns at positions 2, 5, and 6 of the heterocyclic ring, were synthesized in a
      straightforward fashion by means of parallel synthesis and evaluated as
      inhibitors of human immunodeficiency virus type-1 (HIV-1). Most of the compounds
      proved to be highly active on the wild-type enzyme both in enzymatic and cellular
      assays, with one of them emerging as the most active reverse transcriptase
      inhibitor reported so far (EC50wt=25 pM). The general loss of potency displayed
      by the compounds toward clinically relevant mutant strains was deeply studied
      through a molecular modeling approach, leading to the evidence that the dynamic
      of the entrance in the non-nucleoside binding pocket could represent the basis of
      the inhibitory activity of the molecules.

PMID- 18052320
TI  - N,N'-dihydroxyamidines: a new prodrug principle to improve the oral
      bioavailability of amidines.
AB  - N, N'-dihydroxybenzamdine represents a model compound for a new prodrug principle
      to improve the oral bioavailability of drugs containing amidine functions. The
      activation of the prodrug could be demonstrated in vitro by porcine and human
      subcellular enzyme fractions, the mitochondrial benzamidoxime reducing system,
      and porcine hepatocytes. In vivo, the bioavailability of benzamidine after oral
      application of N, N'-dihydroxybenzamidine was about 91% and exceeded that of
      benzamidine after oral application of benzamidoxime, being about 74% (Liu, L.;
      Ling, Y.; Havel, C.; Bashnick, L.; Young, W.; Rai, R.; Vijaykumar, D.; Riggs, J.
      R.; Ton, T.; Shaghafi, M.; Graupe, D.; Mordenti, J.; Sukbuntherng, J. Species
      comparison of in vitro and in vivo conversion of five N-hydroxyamidine prodrugs
      of fVIIA inhibitors to their corresponding active amidines. Presented at the 13th
      North America ISSX Meeting, Maui, HI, 2005).

PMID- 18052321
TI  - Synthesis and antiviral activity of the carbocyclic analogue of the highly potent
      and selective anti-VZV bicyclo furano pyrimidines.
AB  - Carbocyclic nucleoside analogues are catabolically stable since they are
      resistant to phosphorolytic cleavage by pyrimidine nucleoside phosphorylase
      enzymes. The carbocyclic analogue (C-BCNA) of the highly potent and selective
      anti-VZV bicyclic nucleoside analogue (BCNA) 6-pentylphenylfuro[2,3-d]pyrimidine
      2'-deoxyribose was synthesized using carbocyclic 2'-deoxyuridine as starting
      material. C-BCNA was found to be chemically more stable than the furano lead, but
      it was shown to be significantly less antivirally active than its parent
      nucleoside analogue. It was noted to have a 10-fold lower inhibitory activity
      against the VZV-encoded thymidine kinase. This reduction of activity may be
      attributed to the different conformation of the sugar and base, as predicted by
      computational studies and supported by NMR studies. However, other factors
      besides affinity for VZV-TK must account for the greatly reduced antiviral
      potency.

PMID- 18052322
TI  - Structure elucidation of a dihydropyranone from Tapinanthus dodoneifolius.
AB  - A new dihydropyranone, ( R)-6-[( S)-2-hydroxy-4-(4-hydroxyphenyl)butyl]-5,6
      dihydropyran-2-one ( 1), was isolated from Tapinanthus dodoneifolius. The
      structure was determined from spectroscopic and X-ray crystallographic analysis.
      Compound 1 (named dodoneine) showed a relaxing effect on preconstricted rat
      aortic rings (IC 50 of 81.4 +/- 0.9 microM).

PMID- 18052323
TI  - Antifibrotic phenanthrenes of Dendrobium nobile stems.
AB  - Two new phenanthrenes ( 1 and 6) and four new dihydrophenanthrenes ( 2- 5) were
      isolated from a methanolic extract of Dendrobium nobile stems, along with 13
      known phenanthrenes and dihydrophenanthrenes ( 7- 19). By spectroscopic analysis,
      the structures of compounds 1- 6 were determined as 2,8-dihydroxy-3,4,7
      trimethoxyphenanthrene ( 1), 3-hydroxy-2,4,7-trimethoxy-9,10-dihydrophenanthrene
      ( 2), 2,8-dihydroxy-3,4,7-trimethoxy-9,10-dihydrophenanthrene ( 3), 2-hydroxy-4,7
      dimethoxy-9,10-dihydrophenanthrene ( 4), 2,2'-dihydroxy-3,3',4,4',7,7'
      hexamethoxy-9,9',10,10'-tetrahydro-1,1'-biphenanthrene ( 5), and 2,3,5-trihydroxy
      4,9-dimethoxyphenanthrene ( 6), respectively. Antifibrotic activity of compounds
      1- 19 was evaluated employing HSC-T6, an immortalized rat hepatic stellate cell
      line, as an in vitro assay system by assessing cell proliferation.

PMID- 18052324
TI  - Sorbifolivaltrates A-D, diene valepotriates from Valeriana sorbifolia(1).
AB  - Four new diene valepotriates, sorbifolivaltrates A-D ( 1- 4), and the known
      compounds isovaltrate ( 5), valtrate ( 6), seneciovaltrate ( 7), valtrate hydrine
      B3 ( 8), and valtrate hydrine B7 ( 9), have been isolated by bioassay-guided
      fractionation of the cytotoxic hexanes and methyl ethyl ketone crude extracts of
      the aerial parts of Valeriana sorbifolia occurring in the Sonoran desert. The
      structures of 1- 4 were determined on the basis of their high-resolution mass
      spectrometric and NMR spectroscopic data. All compounds exhibited weak to
      moderate cytotoxicity against the human metastatic prostate cancer cell line, PC
      3M.

PMID- 18052325
TI  - Rhizochalins C and D from the sponge Rhizochalina incrustata. A rare threo
      sphingolipid and a facile method for determination of the carbonyl position in
      alpha,omega-bifunctionalized ketosphingolipids.
AB  - Rhizochalins C and D ( 1, 2), new representatives of two-headed
      glycosphingolipids, were isolated from the sponge Rhizochalina incrustata.
      Rhizochalin D is an unexpected C 29 homologue of the canonical C 28 dimeric
      sphingolipid structures. Their structures including absolute configurations were
      established using spectroscopic data, micromolar-scale Baeyer-Villiger oxidation,
      and LCMS interpretation of the products. Application of the latter method leads
      to a revision of the structure of oceanapiside and placement of the keto group at
      C-18 rather than C-11.

PMID- 18052326
TI  - Uncovering biosynthetic potential of plant-associated fungi: effect of culture
      conditions on metabolite production by Paraphaeosphaeria quadriseptata and
      Chaetomium chiversii.
AB  - In an attempt to uncover the biosynthetic potential of plant-associated fungi,
      the effect of culture conditions on metabolite production by Paraphaeosphaeria
      quadriseptata and Chaetomium chiversii was investigated. These studies indicated
      that the production of the major metabolites by P. quadriseptata differ when the
      water used to make the media was changed from tap water to distilled water. It
      resulted in the isolation of six new secondary metabolites, cytosporones F-I ( 1-
      4), quadriseptin A ( 5), and 5'-hydroxymonocillin III ( 6) together with
      monocillin III ( 7), a metabolite new to P. quadriseptata, in addition to
      monocillin I ( 8), a previously known metabolite from this organism. Aposphaerin
      B ( 9) encountered was suspected to be an artifact originating from cytosporone F
      ( 1). Incorporation of heavy metal ions to P. quadriseptata culture medium
      induced production of monocillin I ( 8) by this fungus. Cultivation of C.
      chiversii in liquid medium resulted in the isolation of chaetochromin A ( 12) as
      the major metabolite instead of radicicol ( 10), the major constituent of this
      organism when grown in a solid medium. Compounds 1- 7 and 12 were evaluated for
      their potential to inhibit Hsp90 and antiproliferative activity toward the cancer
      cell lines NCI-H460, MCF-7, and SF-268. Only compounds 6, 7, and 8 exhibited
      significant activity in both assays.

PMID- 18052327
TI  - Nitrogen-containing verticillene diterpenoids from the Taiwanese soft coral
      Cespitularia taeniata.
AB  - Extensive column chromatography of the ethanolic extract of the soft coral
      Cespitularia taeniata collected in Taiwan has resulted in the isolation of eight
      new nitrogen-containing verticillene diterpenes, designated cespitulactams D-K (
      1- 8), together with three known diterpenes, cespitulactams A ( 9) and B ( 10)
      and cespitularin F. In addition, one new derivative, 6- O-acetylcespitulactam F (
      11), was prepared from compound 3. The structures of these compounds were
      elucidated on the basis of spectroscopic analyses, especially HRMS and 2D NMR
      experiments. The cytotoxicity against human oral epidermoid carcinoma (KB) and
      murine L1210 leukemia cell lines and antimicrobial activities of 1- 8 and 11 were
      tested and evaluated. A biogenetic pathway for these novel diterpene alkaloids
      was also proposed.

PMID- 18052329
TI  - Further pterocellins from the New Zealand marine bryozoan Pterocella vesiculosa.
AB  - Four new alkaloids, pterocellins C-F (1-4), have been isolated from the New
      Zealand marine bryozoan Pterocella vesiculosa. Structural elucidation was
      achieved through NMR spectroscopic and mass spectrometric analysis and comparison
      of spectroscopic data with that of the known compounds pterocellins A and B. The
      biological activities of 1-4 were assessed in a number of different assay systems
      and compared with those of pterocellins A and B.

PMID- 18052330
TI  - Sequential palladium-catalyzed coupling reactions on solid-phase.
AB  - Six-types of palladium-catalyzed coupling, Mizoroki-Heck, Migita-Stille,
      Sonogashira, carbonylative esterification, carbonylative Stille, and
      carbonylative Sonogashira reactions, were performed on a polymer support. The
      above coupling reactions of m- and p-substituted aromatic rings, followed by
      carbonylative esterification with m- and p-substituted anisol derivatives were
      carried out in a combinatorial manner. Acid cleavage from the polymer-support
      provided the conjugated aromatic ring systems 1 and 2, which are the core parts
      of rodlike liquid crystals.

PMID- 18052331
TI  - Solid-phase peptide library synthesis on HiCore resin for screening substrate
      specificity of Brk protein tyrosine kinase.

PMID- 18052332
TI  - Asymmetric hydrogenation of prochiral amino ketones to amino alcohols for
      pharmaceutical use.
AB  - This Account gives an overview of the homogeneously catalyzed asymmetric
      hydrogenation of prochiral amino ketones. The preparation of enantiopure
      arylalkanolamines, which are potent and economically very important
      pharmaceuticals, is described. Classical routes of synthesis are compared with
      the new asymmetric hydrogenation route for a number of compounds from the
      viewpoint of an industrial pharmaceutical chemist.

PMID- 18052333
TI  - A scalable approach to combinatorial library design for drug discovery.
AB  - In this paper, we propose an algorithm for the design of lead generation
      libraries required in combinatorial drug discovery. This algorithm addresses
      simultaneously the two key criteria of diversity and representativeness of
      compounds in the resulting library and is computationally efficient when applied
      to a large class of lead generation design problems. At the same time, additional
      constraints on experimental resources are also incorporated in the framework
      presented in this paper. A computationally efficient scalable algorithm is
      developed, where the ability of the deterministic annealing algorithm to identify
      clusters is exploited to truncate computations over the entire data set to
      computations over individual clusters. An analysis of this algorithm quantifies
      the tradeoff between the error due to truncation and computational effort.
      Results applied on test data sets corroborate the analysis and show improvement
      by factors as large as 10 or more, depending on the data sets.

PMID- 18052334
TI  - Electron-structure calculations and bond order analysis using density functional
      theory of cationic dinuclear arene ruthenium complexes.
AB  - The structure and nature of the metal-metal bonding interaction in the cationic
      complexes [(eta6-C6Me6)2Ru2(mu2-H)3]+ (1), [(eta6-C6Me6)2Ru2(mu2-H)2(mu2-1,4
      SC6H4Br)]+ (2), [(eta6-C6Me6)2Ru2(mu2-H)(mu2-1,4-SC6H4Br)2]+ (3), and [(eta6
      C6Me6)2Ru2(mu2-1,4-SC6H4Br)3]+ (4) have been studied at the density functional
      theory (DFT) level using molecular orbital (MO) theory, bond order (BO) analysis,
      bond decomposition energy (BDE), electron localization function (ELF), and
      Laplacian of the density methods. The results show that there is no direct bond
      between the two ruthenium atoms in 1-4, the MO interaction within the diruthenium
      backbone being stabilized by the bridging ligands. For complex 1, the ELF clearly
      shows that the bond within the diruthenium backbone is through the three bridging
      hydride ligands, which act as a sort of glue by forming three-center two-electron
      bonds characterized by (Ru, H, Ru) basins with 1.8 e mostly located in the H
      atomic basin.

PMID- 18052335
TI  - Syntheses, structure, and a Mossbauer and magnetic study of Ba(4)Fe(2)I(5)S(4).
AB  - The compound Ba4Fe2I5S4 has been prepared at 1223-1123 K by the "U-assisted"
      reaction of FeS, BaS, S, and U with BaI2 as a flux. A more rational synthesis was
      also found; however, the presence of U appears to be essential for the formation
      of single crystals suitable for X-ray diffraction studies. Ba4Fe2I5S4
      crystallizes in a new structure type with two formula units in space group I4/m
      of the tetragonal system. The structure consists of a Ba-I network penetrated by
      (1)infinity[Fe2S4] chains. Each Fe atom, which is located on a site with 4
      symmetry, is tetrahedrally coordinated to four S atoms. The FeS4 tetrahedra edge
      share to form linear (1)infinity[Fe2S4] chains in the [001] direction. The Fe-Fe
      interatomic distance in these chains is 2.5630(4) A, only about 3% longer than
      the shortest Fe-Fe distance in -Fe metal. Charge balance dictates that the
      average formal oxidation state of Fe in these chains is +2.5. The Mossbauer
      spectra obtained at 85 and 270 K comprise a single quadrupole doublet that has
      hyperfine parameters consistent with an average Fe oxidation state of +2.5. The
      Mossbauer spectrum obtained at 4.2 K consists of a single magnetic sextet with a
      small hyperfine field of -15.5 T. This spectrum is also consistent with rapid
      electron delocalization and an average Fe oxidation state of +2.5. The molar
      magnetic susceptibility of Ba4Fe2I5S4, obtained between 3.4 and 300 K,
      qualitatively indicates the presence of weak pseudo-one-dimensional ferromagnetic
      exchange within a linear chain above 100 K and weak three-dimensional ordering
      between the chains at lower temperatures.

PMID- 18052336
TI  - Establishment of higher passage PER.C6 cells for adenovirus manufacture.
AB  - PER.C6 cells, an industrially relevant cell line for adenovirus manufacture, were
      extensively passaged in serum-free suspension cell culture to better adapt them
      to process conditions. The changes in cell physiology that occurred during this
      passaging were characterized by investigating cell growth, cell size, metabolism,
      and cultivation of replication-deficient adenovirus. The changes in cell
      physiology occurred gradually as the population doubling level, the number of
      times the cell population had doubled, increased. Higher passage PER.C6 (HP
      PER.C6) proliferated at a specific growth rate of 0.043 h(-1), 2-fold faster than
      lower passage PER.C6, and were capable of proliferation from lower inoculation
      cell densities. HP PER.C6 cell volume was 16% greater, and cellular yields on
      glucose, lactate, oxygen, and amino acids were greater as well. In batch
      cultures, HP PER.C6 cells volumetrically produced 3-fold more adenovirus,
      confirmed with three different constructs. The increase in productivity was also
      seen on a cell-specific basis. Although HP PER.C6 were more sensitive to the
      "cell density effect", requiring lower infection cell densities for optimal
      specific productivity, they proliferated more after infection than lower passage
      PER.C6, increasing the number of cells available for virus production. The
      extensive passaging established HP PER.C6 cells with several desirable attributes
      for adenovirus manufacture.

PMID- 18052338
TI  - Development of an automatic method for americium and plutonium separation and
      preconcentration using an multisyringe flow injection analysis-multipumping flow
      system.
AB  - A new procedure for automatic separation and preconcentration of 241Am and
      239+240Pu from interfering matrixes using transuranide (TRU)-resin is proposed.
      Combination of the multisyringe flow injection analysis and multipumping flow
      system techniques with the TRU-resin allows carrying out the sampling treatment
      and separation in a short time using large sample volumes. Americium is eluted
      from the column with 4 mol L(-1) hydrochloric acid, and then plutonium is
      separated via on-column Pu(IV) reduction to Pu(III) with titanium(III) chloride.
      The corresponding alpha activities are measured off-line, with a relative
      standard deviation of 3% and a lower limit of detection of 0.004 Bq mL(-1), by
      using a multiplanchet low-background proportional counter.

PMID- 18052337
TI  - Identification of Ruta graveolens L. metabolites accumulated in the presence of
      abiotic elicitors.
AB  - The study aimed to elucidate the effects of benzothiadiazole (BTH) and saccharin
      on the biosynthesis of simple coumarins, linear furanocoumarins,
      dihydrofuranocoumarins, and furoquinolone alkaloids in shoots of R. graveolens
      cultivated in vitro. The biosynthesized metabolites were analyzed and identified
      by GC-MS and by comparison of Kovats indices. Eight coumarin metabolites were
      identified: bergapten, chalepin, isopimpinelin, pinnarin, psoralen, rutacultin,
      rutamarin, and xanthotoxin, and also four alkaloids: dictamnine, gamma-fagarine,
      skimmianine, and kokusaginine. Each of the tested BTH concentrations induced a
      significant production of furanocoumarins and furoquinolone alkaloids. The use of
      saccharin also increased the production of bergapten, isopimpinelin, pinnarin,
      psoralen, and xanthotoxin several times.

PMID- 18052339
TI  - Differential metabolomics using stable isotope labeling and two-dimensional gas
      chromatography with time-of-flight mass spectrometry.
AB  - This work describes an approach to differential metabolomics that involves stable
      isotope labeling for relative quantification as part of sample analysis by two
      dimensional gas chromatography/mass spectrometry (GCxGC/MS). The polar metabolome
      in control and experimental samples was extracted and differentially derivatized
      using isotopically light and heavy (D6) forms of the silylation reagent N-methyl
      N-tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA). MTBSTFA derivatives are
      of much greater hydrolytic stability than the more common trimethylsilyl
      derivatives, thus diminishing the possibility of isotopomer scrambling during GC
      analysis. Subsequent to derivatization with MTBSTFA, differentially labeled
      samples were mixed and analyzed by GCxGC/MS. Metabolites were identified, and the
      isotope ratio of isotopomers was quantified. The method was tested using three
      classes of metabolites; amino acids, fatty acids, and organic acids. The relative
      concentration of isotopically labeled metabolites was determined by isotope ratio
      analysis. The accuracy and precision, respectively, in quantification of standard
      mixtures was 9.5 and 4.77% for the 16 amino acids, 9.7 and 2.83% for the mixture
      of 19 fatty acids, and 14 and 4.53% for the 20 organic acids. Suitability of the
      method for the examination of complex samples was demonstrated in analyses of the
      spiked blood serum samples. This differential isotope coding method proved to be
      an effective means to compare the concentration of metabolites between two
      samples simultaneously.

PMID- 18052340
TI  - Analysis of epipolythiodioxopiperazines in fungus Chaetomium cochliodes using
      HPLC-ESI-MS/MS/MS.
AB  - A series of epipolythiodioxopiperazines in the fungus Chaetomium cochliodes was
      investigated using reversed-phase liquid chromatography with diode array
      detection and electrospray quadrupole time-of-flight-type tandem mass
      spectrometry in the positive ion mode. The fragmentation of protonated molecular
      ions including low-abundance parent ions, [M+H]+ for five known
      epipolythiodioxopiperazines, dethiotetra(methylthio)chetomin, chaetocochins A-C,
      and chetomin, was carried out using low-energy collision-induced electrospray
      ionization tandem spectrometry. It was found that McLafferty rearrangements
      occurred in the CID processes and produced a complementary pair of characteristic
      fragment ions containing piperazine rings (fused and unfused), especially to
      determine the number of S atoms on each ring. The fragmentation differential
      between [M+H]+ and [M+Na]+ was uncovered. Complementary fragmentation information
      obtained from [M+H]+ and [M+Na]+ precursor ions is especially valuable for rapid
      identification of epipolythiodioxopiperazines. A likely known compound, possibly
      related to chetoseminudin A, and three new species of epipolythiodioxopiperazines
      from the fungus C. cochliodes were identified or tentatively characterized based
      on tandem mass spectra of known ones.

PMID- 18052341
TI  - Effect of the insulating shield thickness on the steady-state diffusion-limiting
      current of sphere cap microelectrodes.
AB  - The effect of the insulating shield thickness on the steady-state diffusion
      limiting current of sphere cap microelectrodes is investigated. Theoretical
      steady-state limiting currents are obtained by using a simulation procedure,
      which relies on the explicit finite difference method with a fixed time grid and
      an exponentially spatial grid. The results obtained indicate that the current
      increases by decreasing the thickness of the insulating sheath or by increasing
      the aspect ratio of the sphere cap (h/a, where h is the height of the sphere cap
      and a is the electrode basal radius), similarly to other types of microelectrodes
      with different electrode geometry, such as disks and finite cones. The simulated
      data are fitted to approximate analytical expressions to describe the dependence
      of the limiting current on both h/a and RG (RG=b/a, where b is the overall tip
      radius) parameter. Theoretical currents are also compared with experimental data,
      which are obtained with a range of mercury-coated platinum microelectrodes having
      different RG and h/a values. The measurements are performed by using cyclic
      voltammetry at 1 mVs(-1), in aqueous solutions containing Ru(NH3)6-Cl3 as
      electroactive species. A good agreement (within 3%) between theoretical and
      experimental steady-state currents is found. Finally, SECM operating in the
      feedback mode is used to assess the validity of the shape parameters found by
      voltammetry for sphere cap microelectrodes, whose insulating shields are of a
      thickness comparable to the electrode radius.

PMID- 18052342
TI  - Comparison of the practical resolving power of one- and two-dimensional high
      performance liquid chromatography analysis of metabolomic samples.
AB  - Two-dimensional liquid chromatography (2DLC) has become a mainstay of proteomics
      research due to its higher peak capacity compared to one-dimensional LC (1DLC).
      Because of the long analysis times typically associated with 2DLC (tens of hours)
      and its use primarily in proteomics applications, 2DLC in the context of general
      HPLC has been regarded as a niche technique for use in analysis of mixtures
      containing hundreds to thousands of components compared to the far more common
      techniques of isocratic and gradient elution 1DLC. A significant next step in the
      analytical development of 2DLC is to consider using its higher resolving power to
      reduce the analysis time of rather "simple" mixtures, in the range of only tens
      to hundreds of chemical constituents. The chief objective of this paper is to
      provide guidance to practitioners who need to decide whether 1DLC or 2DLC gives
      the superior separation in a given analysis time. Conditional peak capacities are
      predicted for fully optimized 1DLC and practical 2DLC separations of the low
      molecular weight constituents of an extract of corn seed at several analysis
      times using a model based on the chromatographic properties of compounds that are
      representative of real mixtures of lower molecular weight species. Two important
      corrections to the ideal 2DLC peak capacity are made to account for both
      incomplete usage of the separation space and the serious effect of first
      dimension undersampling; this allows, we believe for the first time, a fair
      comparison of the resolving power of 1D- and 2DLC under realistic conditions. The
      predicted optimum conditions are then used to carry out experimental separations
      of low molecular weight corn seed extract, and peaks are counted in each 1D- and
      2DLC chromatogram. Based on comparisons of both the predicted peak capacities and
      number of peaks observed in experimental chromatograms, we believe that practical
      2DLC will be superior to fully optimized gradient 1DLC for separations lasting
      more than only about 10 min. This crossover time is much shorter than intuitively
      expected, and we believe this finding will inevitably have a major impact on the
      practice of 2DLC in liquid-phase separations in general.

PMID- 18052343
TI  - Quantitative comparison between microfluidic and microtiter plate formats for
      cell-based assays.
AB  - In this paper, we compare a quantitative cell-based assay measuring the
      intracellular Ca2+ response to the agonist uridine 5'-triphosphate in Chinese
      hamster ovary cells, in both microfluidic and microtiter formats. The study
      demonstrates that, under appropriate hydrodynamic conditions, there is an
      excellent agreement between traditional well-plate assays and those obtained on
      chip for both suspended immobilized cells and cultured adherent cells. We also
      demonstrate that the on-chip assay, using adherent cells, provides the
      possibility of faster screening protocols with the potential for resolving
      subcellular information about local Ca2+ flux.

PMID- 18052344
TI  - Dynamic cross-linking effect of Mg2+ to enhance sieving properties of low
      viscosity poly(vinylpyrrolidone) solutions for microchip electrophoresis of
      proteins.
AB  - We report a dynamic cross-linking effect of Mg2+ that enhances the sieving
      properties of low-viscosity poly(vinylpyrrolidone) (PVP) solutions. A low
      viscosity PVP solution was applied to nondenaturing microchip electrophoresis of
      protein samples using microchips made of poly(methyl methacrylate). The
      separation resolution of nondenatured protein markers in 1.8% PVP solution was
      improved by adding 1-20 mM MgCl2. We studied the effect of the ratio of cross
      linking agent on mobility of protein samples and showed that protein retardation
      (ln micro/micro0) is correlated with the ratio of cross-linking agent to PVP
      ([cMg2+/cPVP]) as ln micro/micro0=A'[cMg2+/cPVP]b'. A' was related to the protein
      radius (R), and b' was found to be 0.72 for proteins with R=2.4 nm and 0.82 for
      proteins with R=1.85 nm. A structural study of PVP in semidilute solutions using
      dynamic light scattering showed that incremental increases of Mg2+ ion
      concentration from 5 to 20 mM in 1.8% PVP solution increased the hydrodynamic
      radius of PVP polymers by 20%.

PMID- 18052345
TI  - The realm of the nanopore. Interest in nanoscale research has skyrocketed, and
      the humble pore has become a king.

PMID- 18052346
TI  - Catalysis and structural properties of Leishmania infantum glyoxalase II:
      trypanothione specificity and phylogeny.
AB  - The glyoxalase pathway catalyzes the formation of d-lactate from methylglyoxal, a
      toxic byproduct of glycolysis. In trypanosomatids, trypanothione replaces
      glutathione in this pathway, making it a potential drug target, since its
      selective inhibition might increase methylglyoxal concentration in the parasites.
      Two glyoxalase II structures were solved. One with a bound spermidine molecule
      (1.8 A) and the other with d-lactate at the active site (1.9 A). The second
      structure was obtained by crystal soaking with the enzyme substrate (S)-d
      lactoyltrypanothione. The overall structure of Leishmania infantum glyoxalase II
      is very similar to its human counterpart, with important differences at the
      substrate binding site. The crystal structure of L. infantum glyoxalase II is the
      first structure of this enzyme from trypanosomatids. The differential specificity
      of glyoxalase II toward glutathione and trypanothione moieties was revealed by
      differential substrate binding. Evolutionary analysis shows that trypanosomatid
      glyoxalases II diverged early from eukaryotic enzymes, being unrelated to
      prokaryotic proteins.

PMID- 18052347
TI  - Structural elements involved in proton translocation by cytochrome c oxidase as
      revealed by backbone amide hydrogen-deuterium exchange of the E286H mutant.
AB  - Cytochrome c oxidase is the terminal electron acceptor in the respiratory chains
      of aerobic organisms and energetically couples the reduction of oxygen to water
      to proton pumping across the membrane. The mechanisms of proton uptake, gating,
      and pumping have yet to be completely elucidated at the molecular level for these
      enzymes. For Rhodobacter sphaeroides CytcO (cytochrome aa3), it appears as though
      the E286 side chain of subunit I is a branching point from which protons are
      shuttled either to the catalytic site for O2 reduction or to the acceptor site
      for pumped protons. Amide hydrogen-deuterium exchange mass spectrometry was used
      to investigate how mutation of this key branching residue to histidine (E286H)
      affects the structures and dynamics of four redox intermediate states. A
      functional characterization of this mutant reveals that E286H CytcO retains
      approximately 1% steady-state activity that is uncoupled from proton pumping and
      that proton transfer from H286 is significantly slowed. Backbone amide H-D
      exchange kinetics indicates that specific regions of CytcO, perturbed by the
      E286H mutation, are likely to be involved in proton gating and in the exit
      pathway for pumped protons. The results indicate that redox-dependent
      conformational changes around E286 are essential for internal proton transfer.
      E286H CytcO, however, is incapable of these specific conformational changes and
      therefore is insensitive to the redox state of the enzyme. These data support a
      model where the side chain conformation of E286 controls proton translocation in
      CytcO through its interactions with the proton gate, which directs the flow of
      protons either to the active site or to the exit pathway. In the E286H mutant,
      the proton gate does not function properly and the exit channel is unresponsive.
      These results provide new insight into the structure and mechanism of proton
      translocation by CytcO.

PMID- 18052348
TI  - Theoretical analysis of concerted and stepwise mechanisms of Diels-Alder
      reactions of butadiene with silaethylene and disilene.
AB  - The concerted and the stepwise mechanisms of the Diels-Alder reactions of
      butadiene with silaethylene and disilene were studied by ab initio MO methods.
      For the reaction of butadiene and silaethylene, an asymmetric concerted process
      that is almost stepwise and two stepwise processes were located. For the first
      step of the stepwise process, the C-Si bond formation is more favorable than the
      C-C bond formation. The activation energy barrier of the concerted transition
      state is only 0.89 kcal/mol lower than that of the first-step transition state of
      the C-Si bond formation for the stepwise process by the CASPT2 calculation level.
      For the reaction of butadiene and disilene, the activation energy barrier of the
      concerted-type transition state constrained with Cs symmetry is about 9 kcal/mol
      higher than that of the stepwise transition state by the CASSCF method. The
      energy barrier of the first step of the stepwise reaction disappears at the
      CASPT2/6-311++G(d,p) calculation level including the nondynamical correlation
      energy, although the reaction of the butadiene with disilene occurs through the
      stepwise-like process.

PMID- 18052349
TI  - 8-hydroxyquinoline monomer, water adducts, and dimer. Environmental influences on
      structure, spectroscopic properties, and relative stability of cis and trans
      conformers.
AB  - The low fluorescence quantum yield of 8-hydroxyquinoline cannot be correctly
      interpreted without knowing the form that such a compound assumes in different
      environments. The commonly accepted emission-quenching excited-state proton
      transfer can follow different reaction paths if 8-hydroxyquinoline is dimeric or
      monomeric or if it exists in the form of cis and trans conformers; in this light,
      the knowledge of the compound form in a particular environment is basic. We have
      performed a spectroscopic and computational investigation aimed at the
      determination of the form of 8-hydroxyquinoline in different solvents. UV-vis,
      fluorescence, and IR spectral features have been assigned by ab initio
      computations based on the density functional theory and time-dependent density
      functional theory; the density functional theory and MP2 computations have been
      applied to the determination of the relative stability of the dimeric and
      monomeric cis and trans forms of 8-hydroxyquinoline in different solvents.
      Molecular dynamics computations have been used to determine the compound behavior
      in water solutions. According to our results, 8-hydroxyquinoline shows a clear
      preference for the cis conformation (as dimer or monomer), but, in water
      solutions, a small fraction of the trans conformation is also present.

PMID- 18052350
TI  - Conformational structure of some trimeric and pentameric structural units of
      heparin.
AB  - The molecular structure of trimeric units (D-E-F and F-G-H) and the pentamer D-E
      F-G-H of heparin (sodium salts and their anionic forms) was studied using the
      B3LYP/6-31G(d) method. The equilibrium structure of the sodium salts of the
      trimers and pentamer investigated in the isolated state was determined by
      multidentate coordination of the sodium cations with oxygen atoms of the sulfate,
      carboxyl, and hydroxyl (hydroxymethyl) groups, respectively. The displacement of
      Na+ ions from the binding sites in the sodium salt of oligosaccharides studied
      resulted in the appreciable change of the overall conformation of the
      corresponding anion. Upon dissociation, a large change in both the position of
      the sulfate groups and the conformation across the glycosidic bonds was observed.
      The stable energy conformations around the glysosidic bonds found for the
      pentamer investigated are compared and discussed with the available experimental
      X-ray structural data for the structurally related heparin-derived
      pentasaccharides in cocrystals with proteins.

PMID- 18052351
TI  - Photodynamics of polyene-polymethine transformations and spectral fluorescent
      properties of merocyanine dyes.
AB  - Absorption and fluorescence spectrum band moments (center of gravity, width,
      asymmetry, excess, and fine structure) have been determined in a wide range of
      solvents with different polarities for inverse solvatochromic di-, tetra-, and
      hexamethinemerocyanines derived from 1,3-diphenyl-2,3-dihydro-1H-benzimidazole.
      Juxtaposition of the quantum-chemically calculated (by the semiempirical AM1
      method) charges, bond orders, and dipole moments of the merocyanine molecules in
      the ground and excited singlet states with the experimentally observed spectral
      fluorescent characteristics suggests that the molecular electronic structure in
      the two states can vary from a nonpolar polyene via a polymethine to a charge
      separated polyene, depending on the length of the polymethine chain and the
      medium polarity. As shown, solvatofluorochromism gives rise to smaller spectral
      band shifts than those of solvatochromism. This effect is attributable to weaker
      intermolecular solute-solvent interactions in the fluorescent excited state due
      to the more equalized charges as compared to those of the ground state. A lack of
      mirror symmetry of the absorption and fluorescence spectra has been revealed for
      di- and tetramethinemerocyanines (broadened fluorescence bands) as well as for
      hexamethinemerocyanines (narrowed fluorescence bands); the two cases are
      accounted for by the different behavior of vibronic and intermolecular
      interactions in the course of absorption and emission. As found for merocyanines,
      the electronic structure of their fluorescent state approaches the cyanine limit
      and the ground state becomes increasingly polyene-like with lengthening of the
      polymethine chain. A close vicinity of the excited state to the cyanine limit
      causes a dramatic increase in fluorescence quantum yields and a decrease in
      Stokes shifts observed for higher merocyanine vinylogues.

PMID- 18052352
TI  - Matrix isolation infrared spectroscopic and density functional theory studies on
      the reactions of yttrium and lanthanum hydrides with carbon monoxide.
AB  - Laser-ablated yttrium and lanthanum hydrides have been co-deposited at 4 K with
      carbon monoxide in excess argon. Products, such as HYCO, (HY)2CO, HLaCO,
      HLa(CO)2, and H2LaCO, have been formed in the present experiments and
      characterized using infrared spectroscopy on the basis of the results of the
      isotopic shifts, mixed isotopic splitting patterns, stepwise annealing, the
      change of reagent concentration and laser energy, and the comparison with
      theoretical predictions. Density functional theory calculations have been
      performed on these molecules. The agreement between the experimental and
      calculated vibrational frequencies, relative absorption intensities, and isotopic
      shifts supports the identification of these molecules from the matrix infrared
      spectra. Plausible reaction mechanisms have been proposed to account for the
      formation of these molecules.

PMID- 18052353
TI  - Reactions of sulfur dioxide with neutral vanadium oxide clusters in the gas
      phase. I. Density functional theory study.
AB  - Thermodynamics of reactions of vanadium oxide clusters with SO2 are studied at
      the BPW91/LANL2DZ level of theory. BPW91/LANL2DZ is insufficient to properly
      describe relative V-O and S-O bond strengths of vanadium and sulfur oxides.
      Calibration of theoretical results with experimental data is necessary to compute
      reliable enthalpy changes for reactions between VxOy and SO2. Theoretical results
      indicate SO2 to SO conversion occurs for oxygen-deficient clusters and SO2 to SO3
      conversion occurs for oxygen-rich clusters. Stable intermediate structures of VOy
      (y = 1 - 4) clusters with SO2 are also obtained at the BPW91/TZVP level of
      theory. Some possible mechanisms for SO3 formation and catalyst regeneration for
      condensed-phase systems are suggested. These results are in agreement with, and
      complement, gas-phase experimental studies of neutral vanadium oxide clusters.

PMID- 18052354
TI  - Fluorinated diphenylpolyenes: crystal structures and emission properties.
AB  - (E,E,E)-1,6-Diaryl(Ar)-1,3,5-hexatrienes (2, Ar = 4-fluorophenyl; 3, Ar = 2,4
      difluorophenyl; 4, Ar = 2,4,6-trifluorophenyl; 5, Ar = perfluorophenyl) and
      (E,E,E)-1-perfluorophenyl-6-phenyl-1,3,5-hexatriene (6) were prepared. The
      absorption and fluorescence spectra in methylcyclohexane solution showed only a
      small dependence on the fluorine ring substituent, and were similar to those of
      the unsubstituted parent compound (1, Ar = phenyl). The solid-state absorption
      and fluorescence spectra shifted to red relative to those in solution and
      strongly depended on the substituent. The emission from crystals 1-5 originated
      mainly from monomeric species with the maximum wavelength (lambda f(max)) of 440
      465 nm, which overlapped the emission from molecular aggregates (1-4) or
      excimeric species (5) in the red region. Crystal 6 exhibited red-shifted (lambda
      f(max) = 530 nm) and structureless emission due to excimers. The cocrystal of 1
      and 5 (1/5) showed red-shifted (lambda f(max) = 558 nm) and distinctly structured
      emission, not from exciplexes but from the excited states of molecular aggregates
      in which molecules 1 and 5 strongly interact already in the ground state. These
      assignments were confirmed by the results of fluorescence lifetime and quantum
      yield measurements in the solid state. Single-crystal X-ray structure analyses
      showed that the molecules were basically planar in each crystal, whereas the
      crystal packing was strongly substituent-dependent. Weak pi-pi interactions in
      the herringbone (1 and 2) and in the pi-stacked but largely offset structures (3
      and 4) account for their predominantly monomeric origin of emission. The
      observation of excimer fluorescence from 5 was rather unexpected, since the
      molecules in this crystal were arranged in an offset stacking fashion due to
      perfluorophenyl-perfluorophenyl (C6F5...C6F5) interaction. The structures of 6
      and 1/5 considerably resembled each other, in which molecules were pi-stacked
      with more face-to-face geometries than those in 5, as a result of strongly
      attractive perfluorophenyl-phenyl (C6F5...C6H5) interaction. Nevertheless, the
      fluorescence origin was clearly different for 6 and 1/5. This can be ascribed to
      the difference in the strength of orbital-orbital interaction between molecular
      pi-planes in the ground and excited states in crystals.

PMID- 18052355
TI  - Vibronic structure and ion core interactions in Rydberg states of diazomethane:
      an experimental and theoretical investigation.
AB  - Vibronic transitions to the 21A2(3py <-- pi) Rydberg state of CH2N2, CD2N2, and
      CHDN2 were recorded by 2 + 1 REMPI spectroscopy, and kinetic energy distributions
      (eKE) of photoelectrons from ionization of selected vibronic levels were
      determined by velocity map imaging. Normal-mode frequencies were obtained for the
      21A2(3py) Rydberg state and for the cation. Mixed levels of the 21A2(3py) and
      21B1(3pz) of the three isotopologs were identified by photoelectron imaging and
      analyzed. The equilibrium geometries and harmonic vibrational frequencies of the
      electronic states of neutral diazomethane were calculated by CCSD(T)/cc-pVTZ, and
      B3LYP/6-311G(2df,p). The latter method was also used to calculate isotope shifts
      for the ground-state neutral and cation. Geometry and frequencies of the ground
      state of the cation were calculated by CCSD(T)/cc-pVTZ, using the unrestricted
      (UHF) reference. The equilibrium structures, frequencies, and isotope shifts of
      the 21A2(3py) and 21B1(3pz) Rydberg states were calculated by EOM-EE-CCSD/6
      311(3+,+)G(2df). In all cases where comparisons with experimental results were
      available, the agreement between theory and experiment was very good allowing a
      full analysis of trends in structure and vibrational frequencies in going from
      the neutral species to the excited Rydberg states, 21A2(3py) and 21B1(3pz), and
      the cation. Although the 21A2(3py) and 21B1(3pz) states have planar C2v symmetry
      like the ion, they exhibit differences in geometry due to the specific
      interactions of the electron in the 3py and 3pz orbitals with the nuclei charge
      distributions of the ion core. Moreover, trends in normal-mode frequencies in the
      ground states of the neutral and ion and the 21A2(3py) and 21B1(3pz) Rydberg
      states are consistent with removing an electron from the bonding piCN-orbital,
      which also has an antibonding character with respect to NN. To explain the
      observed trends, the vibrational modes are divided into two groups that involve
      displacements mainly (i) along the CNN framework and (ii) in the CH2 moiety.
      Trends in the first group are due mostly to the effect of the lower CN and NN
      bond orders, whereas those in the second group are due to the interaction between
      the positively charged hydrogens and the Rydberg electron density, and the
      hybridization of the carbon. Within each group, marked differences in behavior
      between the in-plane and out-of-plane modes are observed.

PMID- 18052356
TI  - Reactions of hydrogen atom with hydrogen peroxide.
AB  - Rate coefficients are calculated using canonical variational transition state
      theory with multidimensional tunneling (CVT/SCT) for the reactions H + H2O2 -->
      H2O + OH (1a) and H + H2O2 --> HO2 + H2 (1b). Reaction barrier heights are
      determined using two theoretical approaches: (i) comparison of parametrized rate
      coefficient calculations employing CVT/SCT to experiment and (ii) high-level ab
      initio methods. The evaluated experimental data reveal considerable variations of
      the barrier height for the first reaction: although the zero-point-exclusive
      barrier for (1a) derived from the data by Klemm et al. (First Int. Chem. Kinet.
      Symposium 1975, 61) is 4.6 kcal/mol, other available measurements result in a
      higher barrier of 6.2 kcal/mol. The empirically derived zero-point-exclusive
      barrier for (1b) is 10.4 kcal/mol. The electronic structure of the system at
      transition state geometries in both reactions was found to have "multireference"
      character; therefore special care was taken when analyzing electronic structure
      calculations. Transition state geometries are optimized by multireference
      perturbation theory (MRMP2) with a variety of one-electron basis sets, and by a
      multireference coupled cluster (MR-AQCCSD) method. A variety of single-reference
      benchmark-level calculations have also been carried out; included among them are
      BMC-CCSD, G3SX(MP3), G3SX, G3, G2, MCG3, CBS-APNO, CBS-Q, CBS-QB3, and CCSD(T).
      Our data obtained at the MRMP2 level are the most complete; the barrier height
      for (1a) using MRMP2 at the infinite basis set limit is 4.8 kcal/mol. Results are
      also obtained with midlevel single-reference multicoefficient correlation
      methods, such as MC3BB, MC3MPW, MC-QCISD/3, and MC-QCISD-MPWB, and with a variety
      of hybrid density functional methods, which are compared with high-level theory.
      On the basis of the evaluated experimental values and the benchmark calculations,
      two possible recommended values are given for the rate coefficients.

PMID- 18052357
TI  - Mass spectroscopic observation of shock-induced chemistry in liquid CS2.
AB  - We have observed, via time-of-flight mass spectrometry, 13 chemical species more
      massive than CS2 produced by shocking liquid CS2 to very high
      pressure/temperature. The stoichiometry of three of these species is uniquely
      determined from the 12CS2 experiments; these species are C2S2, C3S2, and C4S2.
      The stoichiometry of the other 10 structures cannot be uniquely determined from
      12CS2 experiments. However, by redoing the experiments using isotopically labeled
      CS2 (i.e., 13CS2), we determined the stoichiometry of nine of the remaining
      structures. The nine structures are Sn (n = 3-8) and CS3, C2S5, and C4S6. A
      structure with mass 297.1 amu was also observed in the 12CS2 experiments but was
      not detected in the 13CS2 experiments. This structure must be C6S7, C14S4, or
      C22S; given the low carbon content of the other observed carbon species, it is
      probably C6S7. The shockwaves to which the CS2 molecules were subjected were
      produced by the detonation of high mass-density solid explosives. The explosives
      used were either a plastic bonded form of cyclotetramethlylene tetranitramine or
      pure hexanitrostilbene. Numerical compressible fluid-mechanical simulations were
      done to estimate the pressures, temperatures, and time scales of the processes
      that occurred in the shocked CS2. The results obtained in the present experiments
      are related to earlier work on CS2's chemical reactivity that used both shockwave
      methods and static techniques to produce very high pressure.

PMID- 18052358
TI  - Reversible hydrogen storage property and structural analysis for face-centered
      cubic hydride Mg0.82Zr0.18H2 prepared by gigapascal hydrogen pressure method.
AB  - The face-centered cubic (fcc) type magnesium-zirconium hydride (Mg0.82Zr0.18Hx)
      was synthesized by means of the ultrahigh pressure (UHP) technique, which could
      generate 8 GPa of hydrogen pressure. The differential scanning calorimeter (DSC)
      measurements indicated that the fcc phase exhibited reversible hydrogen releasing
      and restoring properties under 0.5 MPa of hydrogen pressure. On the pressure
      composition isotherms, the released and restored hydrogen capacities were
      estimated to be 3 approximately 3.5 wt %. The Rietveld analysis for synchrotron X
      ray diffraction (XRD) data showed that the fcc phase had around 70 wt % mass
      fraction and was preserved without decomposition during hydrogen releasing and
      restoring cycles.

PMID- 18052359
TI  - Histidine, lysine, and arginine radical cations: isomer control via the choice of
      auxiliary ligand (L) in the dissociation of [CuII(L)amino acid]*2+ complexes.
AB  - Histidine, lysine, and arginine radical cations have been generated through
      collision-induced dissociation (CID) of complexes [CuII(auxiliary ligand)namino
      acid]*2+, using tri-, bi-, as well as monodentate auxiliary ligands. On the basis
      of the observed CID products, the existence of two isomeric amino-acid
      populations is postulated. The Type 1 radical cations of histidine and lysine,
      stable on the mass spectrometer time scale, were found to lose water, followed by
      the loss of carbon monoxide under more energetic CID conditions. The arginine
      Type 1 radical cation behaved differently, losing dehydroalanine. The Type 2
      radical cations were metastable and easily fragmented by the loss of carbon
      dioxide, effectively preventing direct observation. Type 1 radical cations are
      proposed to result from neutral (canonical) amino-acid coordination, whereas Type
      2 radical cations are from zwitterionic amino-acid coordination to copper in the
      complex. The ratio of Type 1/Type 2 ions was found to be dependent on the
      auxiliary ligand, providing a method of controlling which radical cation would be
      formed primarily. Density functional calculations at B3LYP/6-311++G(d,p) have
      been used to determine the relative energies of five His*+ isomers. Barriers
      against interconversion between the isomers and against fragmentation have been
      calculated, giving insight as to why the Type 1 ions are stable, while only
      fragmentation products of the Type 2 ions are observable under CID conditions.

PMID- 18052360
TI  - Adsorption behavior of acidic and basic proteins onto citrate-coated Au surfaces
      correlated to their native fold, stability, and pI.
AB  - The adsorption of eight different proteins (alpha-lactalbumin (types I and III),
      bovine serum albumin, hemoglobin, myoglobin, cytochrome c, alpha-casein, and
      lysozyme) onto a model anionic surface was performed at equivalent bulk (solvent,
      ionic strength, pH) and surface conditions. Adsorption was monitored on a quartz
      crystal microbalance with dissipation monitoring (QCM-D) with citrate-coated gold
      surfaces as adsorbents and has been correlated to native fold stability
      determined from near- and far-UV circular dichroism (CD) measurements. The
      proteins studied here were chosen based on their pI and documented knowledge
      about their structural stability and flexibility. Protein adsorption was found to
      be independent of global protein charge. Rather, binding occurs through
      oppositely charged patches on protein and surface. Moreover, data indicate that
      there is a correlation between secondary and tertiary structure stability and the
      adsorption characteristics at interfaces. Also, protein surface coverage, layer
      thickness, and flexibility can be tuned as a function of deposition method. This
      is discussed in terms of adsorption/spreading kinetics and intermolecular
      (protein-surface and protein-protein) interactions. Adsorption to surfaces can
      induce formation of supramolecular structures such as micelles (in the case of
      alpha-Cas) and multilayers (as for Hb). In the case of alpha-casein, this
      phenomenon depends on the deposition method and protein concentration. When
      ranking the surface coverage for proteins added in excess, the order is Lyz < Cyt
      c < Mb < BSA < alpha-La I < alpha-Cas < alpha-La III < Hb, which can be
      correlated to the proteins ability to form supramolecular structures (alpha-Cas,
      Hb), overall conformational flexibilities, and ability to form stable
      intermediates.

PMID- 18052361
TI  - Raman spectroscopic investigations of pressure-induced phase transitions in n
      hexane.
AB  - We report high-pressure Raman studies on n-hexane up to 16 GPa. n-Hexane
      undergoes solid-solid transition around 9.1 GPa along with an already reported
      liquid-solid transition around 1.4 GPa. The intensity ratio of the Raman modes
      relating the all-trans conformation (1147 and 2872 cm-1) to that of the gauche
      conformation (1074 and 2923 cm-1) shows a sudden change across 9.1 GPa,
      suggesting an increase in the all-trans population conformers above 9.1 GPa. The
      disappearance of the torsional modes suggests a steric hindrance to the methyl
      end group, similar to the n-heptane case, suggesting that the high-pressure phase
      (above 9.1 GPa) is an orientationally disordered phase. In general, the
      transition pressure for the solid-solid transition is inversely proportional to
      the length of the carbon backbone in the medium chain length n-alkanes.

PMID- 18052362
TI  - Metastable States of small-molecule solutions.
AB  - Metastable states such as gels and glasses that are commonly seen in nanoparticle
      suspensions have found application in a wide range of products including
      toothpaste, hand cream, paints, and car tires. The equilibrium and metastable
      state behavior of nanoparticle suspensions are often described by simple fluid
      models where particles are treated as having hard cores and interacting with
      short-range attractions. Here we explore similar models to describe the presence
      of metastable states of small-molecule solutions. We have recently shown that the
      equilibrium solubilities of small hydrogen-bonding molecules and nanoparticles
      fall onto a corresponding-states solubility curve suggesting that with similar
      average strengths of attraction these molecules have similar solubilities. This
      observation implies that metastable states in small-molecule solutions may be
      found under conditions similar to those where metastable states are observed in
      nanoparticle and colloidal suspensions. Here we seek confirmation of this concept
      by exploring the existence of metastable states in solutions of small molecules.

PMID- 18052363
TI  - On the theory of time-resolved X-ray diffraction.
AB  - We derive the basic theoretical formulation for X-ray diffraction with pulsed
      fields, using a fully quantized description of light and matter. Relevant time
      scales are discussed for coherent as well as incoherent X-ray pulses, and we
      provide expressions to be used for calculation of the experimental diffraction
      signal for both types of X-ray sources. We present a simple analysis of time
      resolved X-ray scattering for direct bond breaking in diatomic molecules. This
      essentially analytical approach highlights the relation between the signal and
      the time-dependent quantum distribution of internuclear positions, including
      thermal effects.

PMID- 18052364
TI  - Inhibition of aggregation of a biomimic peptidolipid Langmuir monolayer by Congo
      red studied by UV-vis and infrared spectroscopies.
AB  - A synthetic peptidolipid consisted of a hydrocarbon chain with a chain length of
      C18 and a peptide moiety of IIGLM terminated with an amine group, designated as
      C18IIGLM-NH2, has been employed as a biomimic model compound of amyloid peptide
      for exploring molecular interaction and orientation with the use of the Langmuir
      monolayer and Langmuir-Blodgett film techniques. Inspired by a well-known fact
      that a stain reagent, Congo red (CR), binds well to the amyloid-mimic part
      (IIGLM), inhibition of molecular aggregation of C18IIGLM-NH2 by interaction with
      CR was expected, and it has been investigated by use of surface pressure-area
      isotherm, surface dipole moment-area isotherm, Brewster-angle microscopy, and UV
      vis/infrared spectroscopies. It has been revealed that monomeric CR molecules
      whose long axis is parallel to the Langmuir monolayer surface are penetrating the
      C18IIGLM-NH2 Langmuir monolayer, which plays a role of inhibition of molecular
      aggregation via hydrogen bonding.

PMID- 18052365
TI  - Evaluating rotational diffusion from protein MD simulations.
AB  - It is now feasible to carry out molecular dynamics simulations of proteins in
      water that are long compared to the overall tumbling of the molecule. Here, we
      examine rotational diffusion in four small, globular proteins (ubiquitin, binase,
      lysozyme, and fragment B3 of protein G) with the TIP3P, TIP4P/EW, and SPC/E water
      models, in simulations that are 6 to 60 times as long as the mean rotational
      tumbling time. We describe a method for extracting diffusion tensors from such
      simulations and compare the results to experimental values extracted from NMR
      relaxation measurements. The simulation results accurately follow a diffusion
      equation, even for spherical harmonic correlation functions with l as large as 8.
      However, the best-fit tensors are significantly different from experiment,
      especially for the commonly used TIP3P water model. Simulations that are 20 to
      100 times longer than the rotational tumbling times are needed for good
      statistics. A number of residues exhibit internal motions on the nanosecond time
      scale, but in all cases examined here, a product of internal and overall time
      correlation functions matches the total time-correlation function well.

PMID- 18052366
TI  - Theoretical study of temperature and solvent dependence of the free-energy
      surface of the intramolecular electron-transfer based on the RISM-SCF theory:
      application to the 1,3-dinitrobenzene radical anion in acetonitrile and methanol.
AB  - The free-energy surfaces along the intramolecular electron-transfer reaction path
      of the 1,3-dinitrobenzene radical anion in acetonitrile and methanol are
      investigated with the reference interaction site model self-consistent field
      theory. Although acetonitrile and methanol have similar values of the dielectric
      constant, the free-energy profiles are quite different. In the methanol solution,
      the charge is strongly localized on one of the nitrile substituents due to a
      strong hydrogen bond between 1,3-dinitrobenzene and the solvent, while the
      polarization is not so large in the case of acetonitrile. The temperature
      dependence of the reorganization energy, the coupling strength, and the
      activation barrier is evaluated in both acetonitrile and methanol. The
      reorganization energy and the activation barrier decrease with increasing
      temperature for both cases. The electronic coupling strength also shows a similar
      tendency in the temperature dependence; it increases with increasing temperature
      in both solvents but with different rates. The behavior is explained in terms of
      the strong polarization induced by the hydrogen bond between the solute and
      solvent in the methanol solution.

PMID- 18052367
TI  - Structure and dynamics of poly(T) single-strand DNA: implications toward CPD
      formation.
AB  - The formation of cyclobutane pyrimidine dimers between adjacent thymines by UV
      radiation is thought to be the first event in a cascade leading to skin cancer.
      Recent studies showed that thymine dimers are fully formed within 1 ps of UV
      irradiation, suggesting that the conformation at the moment of excitation is the
      determining factor in whether a given base pair dimerizes. MD simulations on the
      50 ns time scale are used to study the populations of reactive conformers that
      exist at any given time in T18 single-strand DNA. Trajectory analysis shows that
      only a small percentage of the conformations fulfill distance and dihedral
      requirements for thymine dimerization, in line with the experimentally observed
      quantum yield of 3%. Plots of the pairwise interactions in the structures predict
      hot spots of DNA damage where dimerization in the ssT18 is predicted to be most
      favored. The importance of hairpin formation by intra-strand base pairing for
      distinguishing reactive and unreactive base pairs is discussed in detail. The
      data presented thus explain the structural origin of the results from the
      ultrafast studies of thymine dimer formation.

PMID- 18052368
TI  - Dipolar relaxation within the protein matrix of the green fluorescent protein: a
      red edge excitation shift study.
AB  - The fluorophore in green fluorescent protein (GFP) is localized in a highly
      constrained environment, protected from the bulk solvent by the barrel-shaped
      protein matrix. We have used the wavelength-selective fluorescence approach (red
      edge excitation shift, REES) to monitor solvent (environment) dynamics around the
      fluorophore in enhanced green fluorescent protein (EGFP) under various
      conditions. Our results show that EGFP displays REES in buffer and glycerol,
      i.e., the fluorescence emission maxima exhibit a progressive shift toward the red
      edge, as the excitation wavelength is shifted toward the red edge of the
      absorption spectrum. Interestingly, EGFP displays REES when incorporated in
      reverse micelles of sodium bis(2-ethylhexyl)sulfosuccinate (AOT), independent of
      the hydration state. We interpret the observed REES to the constrained
      environment experienced by the EGFP fluorophore in the rigid protein matrix,
      rather than to the dynamics of the bulk solvent. These results are supported by
      the temperature dependence of REES and characteristic wavelength-dependent
      changes in fluorescence anisotropy.

PMID- 18052369
TI  - Theoretical study of cooperativity in biotin.
AB  - To give a deeper insight into the widely discussed catalytic mechanism of biotin,
      four representative model molecules and their aggregates hydrogen bonding (H
      bonding) to water molecules were investigated by means of ab initio calculations
      and compared with molecular dynamics simulations. The roles of the ureido group,
      the sulfur atom, and the side chain of biotin are examined and discussed,
      respectively. Some significant H-bonding cooperativities are theoretically
      demonstrated in the ureido group of biotin. The pi-electron delocalization of the
      ureido group makes the system a good candidate for the H-bonding cooperativities,
      which in turn increases the covalent character of the corresponding H-bonds and
      facilitates the electrophilic substitution of the nitrogen atoms in the ureido
      group. The sulfur of biotin may participate in the delocalized pi-electron system
      of the ureido group via special sulfur-nitrogen bonding interactions, which
      reinforces the H-bonding cooperativities of the ureido group. The side chain of
      biotin not only reduced the accessibility of 3-NH due to steric hindrance but
      also enhanced the H-bonding cooperativities of the ureido group by folding over
      to hydrogen bond to more water molecules. The folded states are a probable way of
      activating 1-NH by strong cooperative effects. In addition, the H-bonding
      cooperativities may be a significant reason for the strong and specific binding
      between biotin and streptavidin.

PMID- 18052370
TI  - Lithium-alkyl, -aryl, and -amido ligand-exchange dynamics of dianionic
      zirconium(IV) complexes with chelating amidophenolate ligands.
AB  - The synthesis, characterization, and solution behavior of a series of six
      coordinate zirconium(IV) dianions [ZrX2(ap)2]2- (ap = 2,4-di-tert-butyl-6-(tert
      butylamido)phenolate; X = Ph, 3a; X = p-tolyl, 3b; X = Me, 4; X = NMe2, 5) are
      described. Complexes 3-5 were prepared by treating the neutral zirconium complex
      Zr(ap)2(THF)2 (1) with 2 equiv of LiX or by the direct reaction of apLi2 and LiX
      with ZrCl4. The complexes were isolated as lithium-etherate salts, and they were
      characterized by NMR spectroscopy and single-crystal X-ray diffraction. In non
      coordinating solvents such as benzene-d6, complexes 3-5 are robust in solution,
      but in coordinating solvents such as THF-d8, dissociation of LiX was observed.
      The rate of LiX loss was evaluated by exchange reactions; the reaction rate
      constants span nine orders of magnitude at 298 K, with the slowest reaction being
      the dissociation of PhLi from 3a (tau1/2 = 4 h) and the fastest reaction being
      the dissociation of LiNMe2 from 5 (tau1/2 = 53 mus). In the case of LiNMe2
      dissociation from 5, activation parameters suggest that the rate-determining step
      is purely dissociative; however, for diphenyl and dimethyl complexes 3a and 4,
      respectively, activation parameters suggest a solvent-assisted rate-determining
      step.

PMID- 18052371
TI  - Reactivity of niobium and tantalum pentahalides with cyclic ethers and the
      isolation and characterization of intermediates in the polymerization of
      tetrahydrofuran.
AB  - The complexes MX5(THF) (M = Nb, X = Cl, 2a; M = Ta, X = F, 2c, X = Cl, 2d) and
      [MX4(THF){O(CH2)4O(CH2)3CH2)}][MX6] (M = Nb, X = Cl, 3a; M = Ta, X = Cl, 3d, X =
      Br, 3e, X = I, 3f) result from reactions of MX5 with 0.5 and 1.5 equiv of THF,
      respectively. Compounds 3 contain the unprecedented 4-(tetrahydrofuran-1-ium)
      butan-1-oxo ligand and are likely to play a role in the course of THF
      polymerization catalyzed by MX5. The addition of L (L = 2,5
      dimethyltetrahydrofuran, tetrahydropyran, 1,4-dioxane) to MX5 results in the
      formation of the hexacoordinated complexes MX5(L). The molecular structures of
      2d, 3d, and NbCl5(dioxane), 6a, have been ascertained by X-ray diffraction
      studies.

PMID- 18052372
TI  - Ternary rare-earth manganese bismuthides: structures and physical properties of
      RE(3)MnBi(5) (RE = La-Nd) and Sm(2)Mn(3)Bi(6).
AB  - Investigations in the ternary RE-Mn-Bi systems where RE is an early rare earth
      element have revealed the existence of the polybismuthides RE3MnBi5 (RE = La-Nd),
      previously known only for the Ce member, and the new compound Sm2Mn3Bi6. Their
      structures were determined from single-crystal X-ray diffraction data. The
      RE3MnBi5 compounds adopt the hexagonal inverse Hf5Cu3Sn-type structure (Pearson
      symbol hP18, space group P63/mcm, a = 9.7139(11)-9.5438(16) A, c = 6.4883(7)
      6.4089(11) A for RE = La-Nd), containing chains of face-sharing Mn-centered
      octahedra. Sm2Mn3Bi6 adopts a new monoclinic structure type (Pearson symbol mP22,
      space group P21/m, a = 10.3917(8) A, b = 4.4557(3) A, c = 13.2793(10) A, beta =
      108.0100(10) degrees ) in which the Mn centers are coordinated by Bi atoms in
      diverse geometries (distorted octahedral, trigonal bipyramidal, and distorted
      tetrahedral (seesaw)) and participate in extensive metal-metal bonding in the
      form of chains of Mn3 clusters. Homoatomic bonding interactions involving
      nominally anionic Bi atoms are manifested as one-dimensional Bi chains in
      RE3MnBi5 and as four-atom-wide Bi ribbons in Sm2Mn3Bi6. Electrical resistivity
      measurements on single crystals revealed metallic behavior with prominent
      transitions near 40 K for RE3MnBi5 and 50 K for Sm2Mn3Bi6. Magnetic
      susceptibility measurements showed that Pr3MnBi5 undergoes magnetic ordering near
      25 K.

PMID- 18052373
TI  - Growth of (WO3)n rectangular structures through a LMO-organic precursor route.
AB  - A LMO-organic (LMO = layered metal oxide) hybrid precursor route has been
      developed to synthesize rectangular (WO3)n structures. In the present work,
      regular rectangular orthorhombic (WO3)n has been fabricated by a thermal
      decomposition of the as-synthesized rectangular [WO3(bpy)0.5]n (bpy = 4,4'
      bipyridine) precursor, which is formed by a process of intercalation,
      coordination, and self-assembly using the hydrothermal treatment of (WO3)n and
      4,4'-bipyridine. The precursor and final products were characterized by field
      emission scanning electron microscopy, transmission electron microscopy, electron
      induced X-ray fluorescence analysis, X-ray diffraction analysis, derivative
      thermogravimetry analysis, and thermogravimetric analysis.

PMID- 18052374
TI  - Ion dynamics and water percolation effects in DNA polymorphism.
AB  - The dynamics of ions and water at the surface of DNA are studied by computer
      simulations in a wide range of hydrations involving the zone of low-hydration
      polymorphism in DNA. The long-range mobility of ions exhibits a stepwise increase
      at three distinct hydration levels. The first of them is close to the midpoint of
      the water percolation transition as well as the midpoint of the transition
      between A- and B-DNA forms. It coincides with the onset of the dissociation of
      ion pairs on the DNA surface probably caused by the increase in the water
      dielectric permittivity due to the appearance of the spanning hydrogen-bonding
      network. The other two steps are attributed to the formation of percolating water
      layers on the surface of DNA accompanied by the progressive escape of ions from
      the DNA surface. The results agree with earlier experimental data and further
      corroborate the suggested universal mechanism of the low hydration polymorphism
      in DNA including intraduplex electrostatic condensation close to the water
      percolation threshold.

PMID- 18052375
TI  - Azobenzene-linked porphyrin-fullerene dyads.
AB  - A new group of porphyrin-fullerene dyads with an azobenzene linker was
      synthesized, and the photochemical and photophysical properties of these
      materials were investigated using steady-state and time-resolved spectroscopic
      methods. The electrochemical properties of these compounds were also studied in
      detail. The synthesis involved oxidative heterocoupling of free base tris-aryl-p
      aminophenyl porphyrins with a p-aminophenylacetal, followed by deprotection to
      give the aldehyde, and finally Prato 1,3-dipolar azomethineylide cycloaddition to
      C60. The corresponding Zn(II)-porphyrin (ZnP) dyads were made by treating the
      free base dyads with zinc acetate. The final dyads were characterized by their 1H
      NMR, mass, and UV-vis spectra. 3He NMR was used to determine if the products are
      a mixture of cis and trans stereoisomers, or a single isomer. The data are most
      consistent with the isolation of only a single configurational isomer, assigned
      to the trans (E) configuration. The ground-state UV-vis spectra are virtually a
      superimposition of the spectral features of the individual components, indicating
      there is no interaction of the fullerene (F) and porphyrin (H2P/ZnP) moieties in
      the ground state. This conclusion is supported by the electrochemical data. The
      steady-state and time-resolved fluorescence spectra indicate that the porphyrin
      fluorescence in the dyads is very strongly quenched at room temperature in the
      three solvents studied: toluene, tetrahydrofuran (THF), and benzonitrile (BzCN).
      The fluorescence lifetimes of the dyads in all solvents are sharply reduced
      compared to those of H2P and ZnP standards. In toluene, the lifetimes of the free
      base dyads are 600-790 ps compared to 10.1 ns for the standard, while in THF and
      BzCN the dyad lifetimes are less than 100 ps. For the ZnP dyads, the fluorescence
      lifetimes were 10-170 ps vs 2.1-2.2 ns for the ZnP references. The mechanism of
      the fluorescence quenching was established using time-resolved transient
      absorption spectroscopy. In toluene, the quenching process is singlet-singlet
      energy transfer (k approximately 10(11) s-1) to give C60 singlet excited states
      which decay with a lifetime of 1.2 ns to give very long-lived C60 triplet states.
      In THF and BzCN, quenching of porphyrin singlet states occurs at a similar rate,
      but now by electron transfer, to give charge-separated radical pair (CSRP)
      states, which show transient absorption spectra very similar to those reported
      for other H2P-C60 and ZnP-C60 dyad systems. The lifetimes of the CSRP states are
      in the range 145-435 ns in THF, much shorter than for related systems with amide,
      alkyne, silyl, and hydrogen-bonded linkers. Thus, both forward and back electron
      transfer is facilitated by the azobenzene linker. Nonetheless, the charge
      recombination is 3-4 orders of magnitude slower than charge separation,
      demonstrating that for these types of donor-acceptor systems back electron
      transfer is occurring in the Marcus inverted region.

PMID- 18052376
TI  - Implementation of a Hamiliton-receptor-based hydrogen-bonding motif toward a new
      electron donor-acceptor prototype: electron versus energy transfer.
AB  - A new modular concept for the self-assembly of electron donor-acceptor complexes
      is presented that ensures (i) fine-tuning the strength of the complexation, (ii)
      controlling the electronic coupling to impact electron and energy transfer
      processes, and (iii) high solubility of the corresponding hybrid architectures.
      This task has been realized through developing a series of porphyrin-fullerene
      donor-acceptor systems held together by a Hamilton-receptor-based hydrogen
      bonding motif. In this context, novel libraries of C60 monoadducts (1) containing
      cyanuric acid side chains and of tetraphenylporphyrin derivatives (2) involving
      the complementary Hamilton-receptor unit were synthesized. The association
      constants of the corresponding 1:1 complexes (1.2) connected by six hydrogen
      bonds were determined complementary by NMR and fluorescence assays. Their
      strength, which was found to be in the range between 3.7 x 10(3) and 7.9 x 10(5)
      M-1, depends on the nature of the spacers, namely, hexylene versus propylene
      chains. Finally, transient absorption studies revealed photoinduced electron
      transfer from ZnP to C60 in the corresponding 1.2 complexes, which generate
      radical ion pair states that are persistent well beyond the ns time scale. In the
      case of the analogous SnP complexes, energy instead of electron transfer was
      observed. This is due to the shift of oxidation potential caused by presence of
      Sn in the oxidation state of +4.

PMID- 18052377
TI  - Common and divergent structural features of a series of corticotropin releasing
      factor-related peptides.
AB  - Members of the corticoliberin family include the corticotropin releasing factors
      (CRFs), sauvagine, the urotensins, and urocortin 1 (Ucn1), which bind to both the
      CRF receptors CRF-R1 and CRF-R2, and the urocortins 2 (Ucn2) and 3 (Ucn3), which
      are selective agonists of CRF-R2. Structure activity relationship studies led to
      several potent and long-acting analogues with selective binding to either one of
      the receptors. NMR structures of six ligands of this family (the antagonists
      astressin B and astressin2-B, the agonists stressin1, and the natural ligands
      human Ucn1, Ucn2, and Ucn3) were determined in DMSO. These six peptides show
      differences in binding affinities, receptor-selectivity, and NMR structure.
      Overall, their backbones are alpha-helical, with a small kink or a turn around
      residues 25-27, resulting in a helix-loop-helix motif. The C-terminal helices are
      of amphipathic nature, whereas the N-terminal helices vary in their
      amphipathicity. The C-terminal helices thereby assume a conformation very similar
      to that of astressin bound to the ECD1 of CRF-R2 recently reported by our group.1
      On the basis of an analysis of the observed 3D structures and relative potencies
      of [Ala]-substituted analogues, it is proposed that both helices could play a
      crucial role in receptor binding and selectivity. In conclusion, the C-terminal
      helices may interact along their hydrophobic faces with the ECD1, whereas the
      entire N-terminal helical surface may be involved in receptor activation. On the
      basis of the common and divergent features observed in the 3D structures of these
      ligands, multiple binding models are proposed that may explain their plurality of
      actions.

PMID- 18052378
TI  - S,C-sulfonium ylides from thiophenes: potential carbene precursors.
AB  - Photolysis of S,C-sulfonium ylides derived from thioanisol, thiophene,
      benzothiophene, or dibenzothiophene provides products deriving from
      dicarbomethoxycarbene. In methanol, no rearrangement of the carbene to the ketene
      derivative is observed. Formation of dibenzothiophene and benzothiophene is
      quantitative. For the thiophene-based ylide, insertion of the carbene into the
      alpha-CH bond of thiophene is observed. Evidence is presented that supports
      formation of both singlet and triplet carbene.

PMID- 18052379
TI  - Unbiased selectivity coefficients obtained for the pulsed chronopotentiometric
      polymeric membrane ion sensors.
AB  - We report here on the successful observation of the unbiased thermodynamic
      selectivity of ion-selective sensors working in normal pulse chronopotentiometric
      mode (pulstrodes). In contrast to ion-selective electrodes, the pulstrodes do not
      require careful counterbalancing of the transmembrane ionic fluxes to achieve
      unbiased thermodynamic selectivity. The pulstrodes can work under asymmetric
      conditions, which are often encountered in practice. The composition of the inner
      filling solution did not affect the sensor response, indicating that the
      transmembrane flux of primary ions was indeed effectively suppressed in the
      absence of ion exchanger. For the K-selective sensor considered here, an
      improvement of Mg discrimination by a factor of 1000 was demonstrated.

PMID- 18052381
TI  - Reactive sulfur species: hydrolysis of hypothiocyanite to give thiocarbamate-S
      oxide.
AB  - Hypothiocyanite (OSCN-) hydrolyzes under alkaline conditions to give
      thiocarbamate-S-oxide (H2NC(=O)SO-, the conjugate base of carbamothioperoxoic
      acid) via a mechanism that involves rate-limiting nucleophilic attack of OH- on
      OSCN-, followed by fast protonation (with no net consumption of H+/OH- at pH
      11.7). Thiocarbamate-S-oxide has been characterized by 13C NMR, 15N NMR, UV
      spectroscopy, and ion chromatography. It has also been independently synthesized
      by the reaction of thiocarbamate (H2NC(=O)S-) and hypochlorite (OCl-). The
      properties of thiocarbamate-S-oxide that is produced by hydrolysis of OSCN- and
      by oxidation of H2NC(=O)S- are the same. The possible relevance of thiocarbamate
      S-oxide in human peroxidase defense mechanisms remains to be explored.

PMID- 18052382
TI  - Oxide-driven carbon nanotube growth in supported catalyst CVD.
AB  - Detailed HREM studies on carbon nanotubes (CNTs) synthesized via chemical vapor
      deposition (CVD) using nanoengineered Fe particles on oxide supports show capped
      tops and open-ended roots. We demonstrate that the pristine catalyst particle
      dictates the CNT diameter and number of walls at nucleation. The consecutive
      inward formation of concentric graphene caps during nucleation constricts and
      elongates the catalyst particle within the tube core. Continued growth stems from
      the oxide support.

PMID- 18052383
TI  - Molecular wires based on thienylethynylene: synthesis, photophysical properties,
      and excited-state lifetime.
AB  - A series of pi-conjugated molecular wires based on thienylethynylene units have
      been developed to understand the effect of the molecular structures on their
      photophysical properties. The investigation of their photophysical properties
      indicates that the formation of aggregates at the ground state is effectively
      suppressed by the incorporation of truxene units. The excited-state lifetimes are
      observed to be biexponential for these molecular wires.

PMID- 18052384
TI  - Efficiency of bulky protic solvent for SN2 reaction.
AB  - We calculate and compare the effects of aprotic vs protic solvent on the rate of
      SN2 reaction [F- + C3H7OMs--> C3H7F + OMs-]. We find that aprotic solvent
      acetonitrile is more efficient than a small protic solvent such as methanol.
      Bulky protic solvent (tert-butyl alcohol) is predicted to be quite efficient,
      giving the rate constant that is similar to that in CH3CN. Our calculated
      relative activation barriers of the SN2 reaction in methanol, tert-butyl alcohol,
      and CH3CN are in good agreement with experimental observations.

PMID- 18052385
TI  - Bichromophoric photochromes based on the opening and closing of a single oxazine
      ring.
AB  - We have designed bichromophoric photochromes based on the photoinduced opening
      and thermal closing of a [1,3]oxazine ring. In particular, we have synthesized
      six compounds incorporating fused 3H-indole and 4-nitrophenoxy fragments and
      pendant biphenyl, styryl, biphenylvinyl, or stilbenylvinyl groups. The laser
      excitation of two of these six molecules cleaves a [C-O] bond and opens their
      [1,3]oxazine ring in less than 6 ns with quantum yields of 0.08 and 0.28,
      respectively. This photoinduced process generates simultaneously a 4
      nitrophenolate anion and a 3H-indolium cation. Both chromophores absorb in the
      same region of the electromagnetic spectrum. As a result, an intense band appears
      at ca. 440 nm upon the photoinduced opening of the [1,3]oxazine ring. In both
      instances, the photogenerated species switches back to the original isomer with
      first-order kinetics and lifetimes of 38 and 140 ns, respectively. Both compounds
      have excellent fatigue resistances and retain their photochemical behavior within
      rigid poly(methyl methacrylate) matrices. However, the thermal reisomerization
      within the polymer matrix is significantly slower and requires several
      microseconds to occur. The other four compounds do not undergo ring opening upon
      excitation under otherwise identical experimental conditions. Indeed, either
      photoinduced electron transfer or intersystem crossing compete successfully with
      the ring-opening process.

PMID- 18052386
TI  - Total synthesis of (-)-hennoxazole A.
AB  - An enantioselective, convergent total synthesis of the antiviral marine natural
      product (-)-hennoxazole A is completed in 14 steps (longest linear sequence) from
      commercially available 4-methyloxazole-2-carboxylic acid. Synthesis of the C(1)
      C(15) pyran/bisoxazole fragment takes advantage of an aldol-like coupling between
      a dimethyl acetal and an N-acetylthiazolidinethione for the direct,
      stereoselective installation of the C(8)-methoxy-bearing stereocenter. A one-pot
      acetoacetate acylation/decarboxylation/cyclodehydration of another elaborate
      thiazolidinethione allows for rapid assembly of the pyran-based ring system.
      Synthesis of the C(15)-C(25) skipped triene side chain fragment makes use of a
      [2,3]-Wittig-Still rearrangement for efficient installation of the trisubstituted
      Z-double bond. Key late-stage coupling of the two fragments is effected by
      deprotonation of the methyl group on the bisoxazole system using lithium
      diethylamide, followed by alkylation with an allylic bromide side chain segment
      to form the C(15)-C(16) bond.

PMID- 18052387
TI  - 3-(Dimethylboryl)pyridine: synthesis, structure, and remarkable steric effects in
      scrambling reactions.
AB  - A facile method for the synthesis of 3-(dimethylboryl)pyridine (1a) is described.
      Compound 1a assembles into a rigid cyclic tetramer stabilized via intermolecular
      boron-nitrogen coordination bonds both in the crystalline state and in solution.
      The outstanding structural feature of 1a, as compared with previously reported 3
      (diethylboryl)pyridine (2a) (which adopts a cone conformation), is that the
      tetramer of 1a adopts a 1,2-alternate conformation. To investigate the effect of
      substituents at the boron atom on the stabilities of the oligomers, scrambling
      experiments of the component molecules using 1, 2, and 3-(di-n
      butylboryl)pyridines 3 were carried out. Although heating at 80-90 degrees C for
      20 h was required to attain the equilibrium of the scrambling reactions when the
      component molecules of the tetramers were 2 or 3, the scrambling in 1 proceeded
      under relatively mild conditions (60 degrees C, 3 h). This difference in reaction
      conditions required for 1, as compared to conditions required for 2 or 3, could
      not be explained solely by the stabilities based on bond lengths or THC. It
      appears that whereas only an S(N)1-type pathway may be involved in the scrambling
      of 2 or 3, both S(N)1- and S(N)2-type mechanisms operate simultaneously during
      scrambling reactions of 1 or an intermediate mechanism between S(N)1 and S(N)2
      operates, which was supported by kinetic studies and calculations using model
      compounds.

PMID- 18052388
TI  - Efficient synthesis of sterically crowded biaryls by palladium-phosphinous acid
      catalyzed cross-coupling of aryl halides and aryl grignards.
AB  - A series of sterically hindered biaryls have been obtained by palladium- and
      nickel-phosphinous acid-catalyzed Kumada-Corriu cross-coupling of ortho
      substituted aryl halides and Grignard reagents. This method allows formation of
      di- and tri-ortho-substituted biaryls in 87-98% yield under mild reaction
      conditions even when electron-rich aryl chlorides are used. The reaction also
      proceeds with aryl iodides at -20 degrees C, and under these conditions,
      functional groups that are generally not compatible with Grignard reagents are
      tolerated.

PMID- 18052389
TI  - Oxazaborolidinone-catalyzed enantioselective Diels-Alder reaction of acyclic
      alpha,beta-unsaturated ketones.
AB  - allo-Threonine-derived O-acyl-B-phenyl-oxazaborolidinones are demonstrated to be
      powerful and highly enantioselective Lewis acid catalysts for the Diels-Alder
      reaction of simple acyclic enone dienophiles, expanding the scope of ketone
      dienophiles and dienes. With 10 to 20 mol % of catalyst, the Diels-Alder adducts
      are obtained in 76-98% ee with high endo-selectivity. The catalyst exhibits high
      activity for the reaction with the less reactive beta-substituted dienophiles and
      the less reactive 1,3-cycohexadiene and 1,3-butadiene derivatives. The
      application of the catalysts to the Diels-Alder reaction of furan is also
      described.

PMID- 18052390
TI  - Rapid and efficient synthesis of dysiherbaine and analogues to explore structure
      activity relationships.
AB  - A rapid and efficient total synthesis of dysiherbaine (1), a potent and subtype
      selective agonist for ionotropic glutamate receptors, has been accomplished. A
      key intermediate 15 was synthesized by two approaches. The first synthetic route
      utilized compound 9, an advanced intermediate in our previous total synthesis of
      neodysiherbaine A, as the starting point, and the cis-oriented amino alcohol
      functionality on the tetrahydropyran ring was installed by using an
      intramolecular S(N)2 cyclization of N-Boc-protected amino alcohol 20. An
      alternative and even more efficient synthetic approach to 15 featured
      stereoselective introduction of an amino group at C8 by iodoaminocyclization
      prior to constructing the bicyclic ether skeleton. The amino acid appendage was
      efficiently constructed by a catalytic asymmetric hydrogenation of enamide ester
      36. The synthetic route developed here provided access to several dysiherbaine
      analogues, including 9-epi-dysiherbaine (38), 9-deoxydysiherbaine (39), 9
      methoxydysiherbaine (40), and N-ethyldysiherbaine (41). The preliminary structure
      activity relationship studies revealed that the presence and stereochemistry of
      the C9 hydroxy group in dysiherbaine is important for high-affinity and selective
      binding to glutamate subtype receptors.

PMID- 18052391
TI  - Synthesis, structure, and conformation of aza[1n]metacyclophanes.
AB  - N-Benzyl substituted aza[1n]metacyclophanes (n = 4, 6, 8, and 10) were prepared
      in overall 40% isolated yields via Pd-catalyzed aminations. Analyses of the
      reaction mixtures showed that aza[14]metacyclophane and the related polymer were
      the primary products ( approximately 60% overall yield); aza[1n]metacyclophanes
      up to n = 14 and linear oligomers with up to 20 nitrogen atoms (with at least
      three types of end groups) were detected. Macrocyclic structures for n = 4, 6,
      and 10 were confirmed by X-ray crystallography. 1,3-Alternate (D(2d)) and 1,3,5
      alternate (S(6)) conformations in solution on NMR time scale at low temperatures
      were found for macrocycles with n = 4 and n = 6, respectively; the barrier for
      ring inversion was considerably lower for the larger macrocycle.

PMID- 18052392
TI  - Phosphabicyclononane-containing ru complexes: efficient pre-catalysts for olefin
      metathesis reactions.
AB  - The catalytic performances of three Phosphabicyclononane (Phoban)-containing
      ruthenium-based pre-catalysts have been evaluated for metathesis transformations.
      A wide screening of substrates in ring-closing metathesis reactions reveals the
      greater efficiency of pre-catalyst 4. Comparison of the catalytic activities of 4
      with Grubbs' first-generation pre-catalyst illustrates the key role of the Phoban
      ligand. Additionally, a comparative study of three Phoban-containing pre
      catalysts has been conducted for the self-metathesis of 1-octene at low catalyst
      loading (25-100 ppm).

PMID- 18052393
TI  - Anthracene derivatives bearing thiourea and glucopyranosyl groups for the highly
      selective chiral recognition of amino acids: opposite chiral selectivities from
      similar binding units.
AB  - Two new anthracene thiourea derivatives, 1 and 2, were investigated as
      fluorescent chemosensors for the chiral recognition of the two enantiomers of
      alpha-amino carboxylates. Especially, host 2 displayed K(L)/K(D) values as high
      as 10.4 with t-Boc alanine. Furthermore, the D/L selectivity of hosts 1 and 2 is
      opposite, even though both hosts bear the same glucopyranosyl units. These
      intriguing opposite D/L binding affinities by 1 and 2 were obtained without/with
      H-pi interaction between anthrancene moiety and the methyl groups, which were
      explained by extensive high-level theoretical investigations taking into account
      the dispersion energy as well as the 2D-NMR chemical shifts.

PMID- 18052394
TI  - Cytochrome p450 and chemical toxicology.
AB  - The field of cytochrome P450 (P450) research has developed considerably over the
      past 20 years, and many important papers on the roles of P450s in chemical
      toxicology have appeared in Chemical Research in Toxicology. Today, our basic
      understanding of many of the human P450s is relatively well-established, in terms
      of the details of the individual genes, sequences, and basic catalytic
      mechanisms. Crystal structures of several of the major human P450s are now in
      hand. The animal P450s are still important in the context of metabolism and
      safety testing. Many well-defined examples exist for roles of P450s in decreasing
      the adverse effects of drugs through biotransformation, and an equally
      interesting field of investigation is the bioactivation of chemicals, including
      drugs. Unresolved problems include the characterization of the minor "orphan"
      P450s, ligand cooperativity and kinetic complexity of several P450s, the
      prediction of metabolism, the overall contribution of bioactivation to drug
      idiosyncratic problems, the extrapolation of animal test results to humans in
      drug development, and the contribution of genetic variation in human P450s to
      cancer incidence.

PMID- 18052395
TI  - Aqueous electrolytes near hydrophobic surfaces: dynamic effects of ion
      specificity and hydrodynamic slip.
AB  - We demonstrate, using molecular-dynamics computer simulations, the strong
      influence of surface wettability on the equilibrium structure of the electrical
      double layer at solid interfaces and on electrokinetic transport in aqueous
      electrolytes due to the effects of interfacial ion specificity and hydrodynamic
      slip. In particular, we show that anomalous electrokinetic effects such as
      nonzero zeta potentials for uncharged surfaces are general features of electro
      osmotic flow in hydrophobic channels for electrolytes with substantial
      cation/anion size asymmetry, as a result of the stronger attraction of the larger
      ion to the "vapor-liquid-like" interface induced by a hydrophobic surface. We
      establish that the simulated velocity profiles obey continuum hydrodynamics on
      the nanoscopic length scales studied and show that the anomalous flow profiles
      can be accurately predicted by using a modified Poisson-Boltzmann description for
      the ion density distributions that incorporates an ion-size-dependent hydrophobic
      solvation energy as a crucial component. We also demonstrate that,
      counterintuitively, the flow for a charge-neutral fluid is independent of the
      solid-fluid friction coefficient.

PMID- 18052396
TI  - Electrochemical surface derivatization of glassy carbon by the reduction of
      triaryl- and alkyldiphenylsulfonium salts.
AB  - The range of materials susceptible to electrochemically assisted grafting onto
      carbon materials has been expanded to include a new group of compounds. This new
      approach is based on the reduction of symmetrical or unsymmetrical
      triarylsulfonium salts and alkyldiphenylsulfonium salts. Our findings suggest
      that it is possible to form layers of aryl moieties on the surface and that the
      unsymmetrical triarylsulfonium salts cleave upon reduction in a direction
      dictated by the substituent on the rings (i.e., (4
      methoxyphenyl)diphenylsulfonium salt leads to a film made predominantly of phenyl
      groups, whereas (4-chlorophenyl)diphenylsulfonium salt leads to a mixture of
      phenyl and chlorophenyl groups). These relationships may be understood by
      considering the inductive nature of the substituent with regard to the aryl-S
      bonds and are supported by preparative experiments. Upon reduction, the
      alkyldiphenylsulfonium salts are found to cleave almost exclusively to an alkyl
      radical and diphenyl sulfide. As judged from the electrochemical blocking
      properties of the films made from such species, either relatively thick or
      compact films are formed. The mass spectrometric analysis indicates that the
      films are made of a combination of alkyl and aryl groups and possibly related
      structural derivatives. Importantly, our findings provide evidence that it is
      possible to graft electrode surfaces with reactive aryl radicals even using
      precursors reduced at potentials that are substantially more negative than the
      estimated reduction potential of the grafting radical.

PMID- 18052397
TI  - Gentle immobilization of nonionic polymersomes on solid substrates.
AB  - Vesicles from Pluronic L121 (PEO5-PPO68-PEO5) triblock copolymers were first
      stabilized by a permanent interpenetrating polymer network and then gently
      immobilized onto a glass or mica surface. Fluorescence-labeled micrometer-sized
      vesicles were visualized with confocal laser scanning microscopy, and smaller
      sized capsules, around 100 nm, were probed by liquid atomic force microscopy. The
      immobilized vesicles were weakly attached to a negatively charged surface via
      negatively charged polyelectrolytes in combination with Mg2+ ions and can be
      reversibly detached from the surface by slightly elevated temperatures. To
      illustrate that the immobilized vesicles remain responsive to external stimuli,
      we show that it is possible to transform their shape from spherical to
      cylindrical by introducing a second Pluronic, namely, P123 (PEO20-PPO70-PEO20).
      The detailed transition process has been recorded in real time by confocal laser
      scanning microscopy. Electron microscopy studies confirmed that a similar
      morphology change also occurs in the bulk.

PMID- 18052398
TI  - Azide-derivatized gold nanorods: functional materials for "click" chemistry.
AB  - We describe herein the synthesis of functional gold nanorods suitable for
      carrying out "click" chemistry reactions. Gold nanorods modified with a copolymer
      containing sulfonate and maleic acid groups have been conjugated to a
      bifunctional azide molecule (amine-PEG-azide). The maleic acid molecules in the
      copolymer participate in carbodiimide-mediated amide bond formation with amine
      groups of the azide linker, whereas the sulfonate groups prevent nanorod
      aggregation in water. Spectroscopic and zeta-potential measurements have been
      used to confirm the successful surface modification of the gold nanorods. These
      azide-functionalized nanorods can carry out chemical reactions based on click
      chemistry. As a case study, we have demonstrated the "clicking" of azide-nanorods
      to an acetylene-functionalized enzyme, trypsin, by a copper-catalyzed 1,3-dipolar
      cycloaddition reaction. The enzyme is not only stable after bioconjugation but is
      also biologically active, as demonstrated by its digestion of the protein casein.
      For comparison, the biological activity of trypsin conjugated to gold nanorods by
      two other commonly used methods (carbodiimide-mediated covalent attachment via
      amide bond formation and simple electrostatic adsorption) has been studied. The
      enzyme conjugated by click chemistry demonstrates improved biological activity
      compared with other forms of bioconjugation. This general and simple approach is
      easy, specific with higher yields, environmentally benign, and applicable to a
      wide range of analytes and biomolecules.

PMID- 18052399
TI  - PVA-DNA cryogel membranes: characterization, swelling, and transport studies.
AB  - Double-stranded (ds) DNA from salmon testes has been incorporated into PVA
      hydrogels obtained by a technique of repeated freezing and thawing. The cryogels
      obtained are free of potential toxic species like chemical cross-linkers, and
      consequently, they can be used in pharmaceutical or medical applications. These
      cryogels show a good mechanical resistance and a white and opaque appearance
      caused by a heterogeneous porous structure. Encapsulated DNA molecules can be in
      a compacted or an extended conformation in the PVA matrix and can be controlled
      by tailoring the degree of crystallinity of the PVA network; this is supported by
      fluorescence microscopy and UV and FTIR spectroscopic studies. The two forms of
      encapsulated DNA were observed for different types of matrixes: an extended one
      in a more crystalline network and a globular one in a more amorphous one.
      Different associations of base pairs have also been observed. PVA cryogel
      crystallinity could be tailored by the cryogel contact with different salt
      solutions. Cryogel surface (scanning electron microscopy) and bulk morphology
      (porosimetry), swelling, DNA retention, and delivery kinetics have also been
      studied. All these investigations clearly show strong interactions between PVA
      and DNA.

PMID- 18052400
TI  - Adsorption and co-adsorption of ethylene and carbon monoxide on silica-supported
      monodisperse Pt nanoparticles: volumetric adsorption and infrared spectroscopy
      studies.
AB  - The adsorption of carbon monoxide and ethylene, and their sequential adsorption,
      was studied over a series of Pt/SBA-15 catalysts with monodisperse particle sizes
      ranging from 1.7 to 7.1 nm by diffuse-reflectance infrared spectroscopy and
      chemisorption. Gas adsorption was dependent on the Pt particle size, temperature,
      and sequence of gas exposure. Adsorption of CO at room temperature on Pt/SBA-15
      gives rise to a spectroscopic feature assigned to the C-O stretch: nu(CO) = 2075
      cm-1 (1.9 nm); 2079 cm-1 (2.9 nm); 2082 cm-1 (3.6 nm); and 2090 cm-1 (7.1 nm).
      The intensity of the signal decreased in a sigmoidal fashion with increasing
      temperature, thereby providing semiquantitative surface coverage information.
      Adsorption of ethylene on Pt/SBA-15 gave rise to spectroscopic features at
      approximately 1340, approximately 1420, and approximately 1500 cm-1 assigned to
      ethylidyne, di-sigma-bonded ethylene, and pi-bonded ethylene, respectively. The
      ratio of these surface species is highly dependent on the Pt particle size. At
      room temperature, Pt particles stabilize ethylidyne as well as di-sigma- and pi
      bonded ethylene; however, ethylidyne predominated on the surfaces of larger
      particles. Ethylidyne was the only identifiable species at 403 K, with its
      formation being more facile on larger particles. Co-adsorption experiments reveal
      that the composition of the surface layer is dependent on the order of exposure
      to gases. Exposure of a C2H4-covered Pt surface to CO resulted in an
      approximately 50% decrease in chemisorbed CO compared to a fresh Pt surface. The
      nu(CO) appeared at 2050 cm-1 on Pt/SBA-15 pretreated with C2H4 at room
      temperature. The di-sigma-bonded and pi-bonded species are the most susceptible
      to displacement from the surface by CO. The formation of ethylidyne appeared to
      be less sensitive to the presence of adsorbed carbon monoxide, especially on
      larger particles. Upon exposure of C2H4 to a CO-covered Pt surface, little
      irreversible uptake occurred due to nearly 100% site blocking. These results
      demonstrate that carbon monoxide competes directly with ethylene for surface
      sites, which will have direct implications on the poisoning of the
      heterogeneously catalyzed conversion of hydrocarbons.

PMID- 18052401
TI  - Solubilization of n-alkylbenzenes into decanoyl-N-methylglucamide (Mega-10)
      solution.
AB  - Solubilization of benzene, toluene, ethylbenzene, n-propylbenzene, n
      butylbenzene, n-pentylbenzene, and n-hexylbenzene into micelles of decanoyl-N
      methylglucamide (Mega-10) was studied, where equilibrium concentrations of the
      above solubilizates were determined spectrophotometrically at 303.2 K. The
      concentration of the above solubilizates remained constant below the critical
      micelle concentration (cmc) and increased linearly with an increase in Mega-10
      concentration above the cmc. The Gibbs free energy change of the solubilizates
      from the aqueous bulk to the liquid solubilizate phase was evaluated from the
      dependence of their aqueous solubility on the alkyl chain length of the
      solubilizates, which leads to -3.46 kJ mol-1 for DeltaG(0)(CH), the energy change
      per CH2 group of the alkyl chain. The first stepwise solubilization constant
      (K(overline)1 ) was evaluated from the slope of the change of solubilizate
      concentration versus Mega-10 concentration. The Gibbs free energy change
      (DeltaG(0,s)) for the solubilization decreased linearly with the carbon number of
      the alkyl chain of the solubilizates, from which DeltaG(0,s)(CH2) as evaluated to
      be -2.71 kJ mol-1. The similar values above clearly indicate that the location of
      the alkyl chain is a hydrophobic micellar core, which is also supported by the
      absorption spectrum of the solubilized molecules.

PMID- 18052402
TI  - Use of negative capacitance to provide voltage amplification for low power
      nanoscale devices.
AB  - It is well-known that conventional field effect transistors (FETs) require a
      change in the channel potential of at least 60 mV at 300 K to effect a change in
      the current by a factor of 10, and this minimum subthreshold slope S puts a
      fundamental lower limit on the operating voltage and hence the power dissipation
      in standard FET-based switches. Here, we suggest that by replacing the standard
      insulator with a ferroelectric insulator of the right thickness it should be
      possible to implement a step-up voltage transformer that will amplify the gate
      voltage thus leading to values of S lower than 60 mV/decade and enabling low
      voltage/low power operation. The voltage transformer action can be understood
      intuitively as the result of an effective negative capacitance provided by the
      ferroelectric capacitor that arises from an internal positive feedback that in
      principle could be obtained from other microscopic mechanisms as well. Unlike
      other proposals to reduce S, this involves no change in the basic physics of the
      FET and thus does not affect its current drive or impose other restrictions.

PMID- 18052403
TI  - Controlled fabrication and electrical properties of long quasi-one-dimensional
      superconducting nanowire arrays.
AB  - We report a general method for reliably fabricating quasi-one-dimensional
      superconducting nanowire arrays, with good control over nanowire cross section
      and length, and with full compatibility with device processing methods. We
      investigate Nb nanowires with individual nanowire cross sectional areas that
      range from bulklike to 10 x 11 nm, and with lengths from 1 to 100 microm.
      Nanowire size effects are systematically studied. In particular, a comprehensive
      investigation of influence of nanowire length on superconductivity is reported
      for the first time. All results are interpreted within the context of phase-slip
      models.

PMID- 18052405
TI  - Symposium on Better Medicines for Children: report from the 25th International
      Congress of Pediatrics, Athens, Greece.
AB  - A symposium on Better Medicines for Children at the 25th International Congress
      of Pediatrics in Athens, Greece, in August 2007 drew attention to the worldwide
      needs for suitable and available medicines for children, and described recent
      forward action in this important area.

PMID- 18052406
TI  - Optimizing therapy with antibacterial agents: use of pharmacokinetic
      pharmacodynamic principles in pediatrics.
AB  - The appropriate dosage of antibacterial agents is essential in achieving both
      clinical and microbiologic success in the treatment of infections in children. By
      using in vitro experimental data and animal model outcome data, the
      pharmacokinetic-pharmacodynamic (PK-PD) parameters predictive of antibacterial
      effect have been elucidated. For time-dependent drugs such as beta-lactams, the
      PK-PD parameter of interest is the percentage of time in a dosage interval for
      which drug concentrations remain above the minimum inhibitory concentration (MIC)
      of the infecting organism. For concentration-dependent drugs such as
      aminoglycosides, the PK-PD parameter of interest is the ratio of the area under
      the plasma concentration-time curve to the MIC. Recent studies using data on
      clinical and microbiologic outcomes from infected adults and children, combined
      with data on drug exposure, have confirmed the importance of these parameters and
      provided estimates of the PK-PD goals of therapy for various antibacterial
      agents. Application of these PK-PD principles allows rational dosage regimen
      selection, both for serious infections in critically ill children and for non
      life-threatening community-acquired infections.

PMID- 18052407
TI  - Targeted B-cell depletion therapy in childhood-onset systemic lupus
      erythematosus: progress to date.
AB  - Childhood-onset systemic lupus erythematosus (SLE) is a multisystemic autoimmune
      disease associated with significant morbidity and mortality with lupus nephritis
      being a major prognostic factor. Children with SLE tend to have more severe
      hematologic and renal involvement compared with adults. Although the morbidity
      and mortality have greatly improved over the last 20 years, recent studies show
      that there are still associated major risks from under treatment (with resultant
      severe flares of disease activity) and over treatment (with additional medication
      adverse effects including risks of severe infection; many of these patients have
      inherent abnormal complement pathways). Therapies used to treat children with SLE
      need to be individualized based on multiorgan involvement, severity of disease,
      history of disease flares, and knowledge of recent relevant clinical,
      hematologic, and immunologic parameters. These medications need to be the most
      effective treatments, allowing normal growth, development, fertility, and the
      avoidance of severe toxicity and future malignancies. Many toxic effects of
      current medications range from the well described Cushingoid features of
      corticosteroids to the gastrointestinal adverse effects of mycophenolate mofetil.
      In vitro studies have shown that rituximab causes B-cell depletion by mechanisms
      involving antibody-dependent cell-mediated cytotoxicity, complement-dependent
      cytotoxicity, and direct signaling leading to apoptosis. As the adverse effect
      profile of B-cell depletion with rituximab has been well described in adults and
      children with oncologic and other autoimmune diseases, initial pilot studies
      using rituximab in patients with refractory SLE have been carried out according
      to different protocols. Evidence to date in open studies demonstrates that
      targeted B-cell depletion therapy can be safe and efficacious as an addition to
      standard immunosuppressant agents in refractory childhood-onset and adult-onset
      disease. Although there are positive outcomes in using this therapy, caution is
      necessary with respect to minimizing the number of doses and treatments given to
      reduce the incidence of developing human anti-chimeric antibodies. The next phase
      for the clinical and research community are multicenter randomized controlled
      trials of rituximab in severe childhood SLE, such as a comparative trial of
      rituximab versus intravenous cyclophosphamide in patients both at presentation
      and with exacerbations of disease activity.

PMID- 18052408
TI  - Pediatric overactive bladder syndrome: pathophysiology and management.
AB  - Detrusor overactivity, also known as the overactive bladder syndrome (OAB), urge
      syndrome, hyperactive bladder syndrome, persistent infantile bladder, and
      detrusor hypertonia, is the most common voiding dysfunction in children. Until
      recently, the concepts that had been used to dictate the management of this
      problem in children were based on the foundation that this was a primary bladder
      problem and or a delay in maturation in the nervous system of children. The
      expectation that children would outgrow their problems led many pediatric
      urologists and other practitioners to tell the parents of these children 'that
      they would not be wetting themselves on their wedding day.' However, it has
      become apparent from recent studies in adult patients with voiding dysfunctions
      that they had symptoms present as children. Recent findings of associations
      between lower urinary tract symptoms and sexual dysfunction and between voiding
      dysfunctions and neuropsychiatric problems have opened up a new frontier into the
      possible mechanisms of OAB in children that would explain these problems, link
      them together, and explain the continued problems that adult patients face. These
      findings point to OAB as a symptom of a more centrally located dysfunction that
      affects multiple systems. The objective of this review was to evaluate the
      neuroanatomy and neurophysiology of voiding and neuropharmacologic effects. We
      considered not only the available research and clinical data within the urologic
      field but also outside the field so that these data could be combined to generate
      a unified theory that could possibly explain many of the associated symptoms that
      are commonly found in pediatric OAB. Treatment modalities that are currently
      available for managing OAB were also explored. Currently available data indicate
      that pediatric OAB and many pediatric voiding dysfunctions may be part of a more
      generalized problem that affects multiple systems: notably bowels, bladder,
      sexual and ejaculatory function, control of blood pressure, and even mood and
      behavior. We explain the relationship that the bowel has with pediatric OAB and
      also the link that other neuropsychiatric problems have with OAB. This article
      describes which drug may be best suited to treat OAB in children and what
      treatment modalities are available when first-line drugs fail. In conclusion, the
      movement away from a vesicocentric way of thinking to a more corticocentric mode
      of thinking along with new imaging modalities that can examine the brain as it
      works will be of great value in determining future treatments of OAB. Medications
      generated from these evidence-based studies will hopefully treat the underlying
      disease process and not just the symptoms.

PMID- 18052409
TI  - Optimal management strategies for rhabdomyosarcoma in children.
AB  - Rhabdomyosarcoma is the most common sarcoma of childhood. Fortunately, the goal
      of cure is realistic for the majority of patients with localized tumors. However,
      management of these patients remains challenging. The fact that the tumor arises
      in a wide variety of primary sites, some of which are associated with specific
      patterns of local invasion, regional lymph node spread, and therapeutic response,
      requires physicians to be familiar with site-specific staging and treatment
      details. In addition, rhabdomyosarcoma requires multimodality therapy that can be
      associated with significant acute toxicities and long-term effects, particularly
      when administered to young children. These factors sometimes present a dilemma as
      to the best approach to optimize the chance of cure, minimize toxicity, and
      respect quality of life. The purpose of this review is to discuss 'optimal'
      management of this complicated tumor. Since the tumor is relatively rare,
      requires highly specialized care, and important management questions remain to be
      answered, optimal management of rhabdomyosarcoma includes enrollment in clinical
      trials whenever possible. Appropriate management begins with establishing the
      correct pathologic diagnosis, histologic subtype, primary site, extent of disease
      (International Society of Pediatric Oncology [SIOP]-TNM-Union Internationale
      Contre le Cancer stage or Intergroup Rhabdomyosarcoma Study Group [IRSG] stage),
      and extent of resection (IRSG group). Cooperative groups throughout North America
      and Europe have defined risk-adapted treatment based on these factors; this
      treatment requires a coordinated management plan that includes surgery,
      chemotherapy, and usually radiotherapy. The surgical approach for
      rhabdomyosarcoma is to excise the primary tumor whenever possible without causing
      major functional or cosmetic deficits. Wide excision is difficult in some primary
      sites and can be complicated by the fact that the tumor grows in a locally
      infiltrative manner so that complete resection is often neither possible nor
      medically indicated. Incompletely resected tumors are generally treated with
      radiotherapy. The cooperative groups reduce the dose of radiation based on the
      response of the tumor to chemotherapy and delayed primary resection to differing
      degrees. Response-adjusted radiation administration may reduce the long-term
      effects of radiotherapy, such as bone growth arrest, muscle atrophy, bladder
      dysfunction, and induction of second malignant neoplasms; however, it may also be
      associated with an increased risk of tumor recurrence. All patients with
      rhabdomyosarcoma require chemotherapy. A backbone of vincristine and dactinomycin
      with either cyclophosphamide (VAC) or ifosfamide (IVA) has been established. Risk
      adapted treatment involves reducing or eliminating the alklyating agent for
      patients with the most favorable disease characteristics. Clinical trials are
      ongoing to improve outcomes for higher risk patients; newer agents, such as
      topotecan or irinotecan, in combination with VAC or use of agents in novel ways
      are being investigated. Acute and long-term toxicities associated with these
      chemotherapy regimens include myelosuppression, febrile neutropenia, hepatopathy,
      infertility, and second malignant neoplasms. A 5-year survival rate >70% has been
      achieved in recent trials for patients with localized rhabdomyosarcoma. However,
      the outcome for patients who present with metastatic disease remains poor. In the
      future, risk-adapted classification of rhabdomyosarcoma will likely be based on
      biologic features, such as the presence of chromosomal translocations or specific
      gene expression profiles. It is hoped that newer therapies directed at specific
      molecular genetic defects will benefit all patients with rhabdomyosarcoma.

PMID- 18052410
TI  - Management of community-acquired pneumonia in children.
AB  - Community-acquired pneumonia (CAP) is a significant cause of childhood morbidity
      and mortality worldwide. Viral etiology is most common in young children and
      decreases with age. Streptococcus pneumoniae is the single most common bacterial
      cause across all age groups. Atypical organisms present similarly across all age
      groups and may be more common than previously recognized.A bacterial pneumonia
      should be considered in children presenting with fever >38.5 degrees C,
      tachypnea, and chest recession. Oxygen therapy is life saving and should be given
      when oxygen saturation is <92%. For non-severe pneumonia, oral amoxicillin is the
      antibacterial of choice with low failure rates reported. Severely ill children
      are traditionally treated with parenteral antibacterials. Penicillin non
      susceptible S. pneumoniae prevalence rates are increasing and have been linked to
      community antibacterial prescribing. Most pneumococci remain sensitive to high
      dose penicillin-based antibacterials but macrolide resistance is also a problem
      in some communities. However, primary combination treatment with macrolides is
      indicated in areas where there is a high prevalence of atypical organisms. The
      most common complications in CAP are parapneumonic effusions and empyema. The use
      of ultrasonography combined with intercostal drainage augmented with the use of
      fibrinolytic therapy has significantly reduced the morbidity associated with
      these complications. There is increasing evidence that a preventative strategy
      with the 7-valent pneumococcal conjugate vaccine (PCV-7) results in a significant
      fall in CAP in early childhood.

PMID- 18052411
TI  - Systemic hypertension and proteinuria in childhood chronic renal parenchymal
      disease: role of antihypertensive drug management.
AB  - A variety of chronic kidney diseases tend to progress towards end-stage kidney
      disease. Progression is largely due to factors unrelated to the initial disease,
      including systemic hypertension and proteinuria. Drugs that block the renin
      angiotensin II-aldosterone system, either ACE inhibitors or angiotensin II
      receptor antagonists, reduce both BP and proteinuria and appear superior to a
      more conventional antihypertensive treatment regimen in preventing progression to
      end-stage kidney disease. The most recent recommendations state that the BP goal
      in children with chronic kidney disease is the corresponding 90th centile for
      body height, age, and gender. Since satisfactory BP control is often not
      achieved, the mnemonic acronym DELTAREPROSI was generated to recall the following
      tips for the practical management of hypertension and proteinuria in childhood
      chronic renal parenchymal disease: DEfinition of hypertension and Low blood
      pressure TArget in REnal disease (90th centile calculated by means of simple
      formulas), potential of drugs inhibiting the REnin-angiotensin II-aldosterone
      system in hypertension and PROteinuria, advantages of SImplified treatment
      regimens and escalating the doses every SIx weeks.

PMID- 18052413
TI  - Coherent control of bond breaking in amino acid complexes with tailored
      femtosecond pulses.
AB  - Intense femtosecond laser pulses, judiciously tailored in an adaptive, optimal
      control feedback loop were used to break preferentially the acyl-N ("peptide")
      bond of Ac-Phe-NHMe that may be regarded as a dipeptide model. We show that
      coherent excitation of complex wave packets in the strong-field regime allows to
      cleave strong backbone bonds in the molecular system preferentially, while
      keeping other more labile bonds intact. These results show the potential of pulse
      shaping as a powerful complementary analytical tool for protein sequencing of
      large biopolymers in addition to the well-known mass spectrometry and chemical
      analysis.

PMID- 18052412
TI  - Aripiprazole: in adolescents with schizophrenia.
AB  - Aripiprazole is a novel atypical antipsychotic that is approved in the US for use
      in adolescents with schizophrenia. In adolescents with schizophrenia, oral
      aripiprazole 10 or 30 mg/day lead to significantly greater reductions than
      placebo in the Positive and Negative Syndrome Scale (PANSS) total score from
      baseline to 6 weeks, according to findings from a randomized, double-blind,
      multicenter trial (n = 302). In addition, aripiprazole 10 or 30 mg/day recipients
      had significantly greater improvements in the PANSS positive subscale and
      Clinical global Impression-Severity and -Improvement scale scores than placebo
      recipients, and a significantly greater improvement in the PANSS negative
      subscale score was seen with aripiprazole 10 mg/day than with placebo.
      Aripiprazole was generally well tolerated in adolescents with schizophrenia, with
      most adverse events being of mild to moderate severity. Clinically significant
      weight gain (> or = 7% as defined by the US FDA) occurred in 4.0% of aripiprazole
      10 mg/day recipients, 5.2% of aripiprazole 30 mg/day recipients, and 1% of
      placebo recipients. The mean weight change was significantly different in
      aripiprazole and placebo recipients (0, +2, and -0.8 kg in aripiprazole 10
      mg/day, aripiprazole 30 mg/day, and placebo recipients, respectively).

PMID- 18052414
TI  - Circular dichroism of helical structures using semiempirical methods.
AB  - A general semiempirical scheme has been elaborated to simulate circular dichroism
      (CD) spectra of supramolecular systems. This approach adopts the analytical
      method of Beck and Hohlneicher [Theor. Chem. Acc. 101, 297 (1999).] to evaluate
      the one- and two-center integrals over Slater atomic orbitals. The performance of
      the method, employing INDO/S and CNDO/S semiempirical parametrizations, has been
      assessed by considering (i) the effect of the size of the singly excited states
      manifold, (ii) the origin invariance, and (iii) comparisons with the experimental
      and other theoretical spectra of several helicenes as well as pyridine-pyrimidine
      oligomers, which can adopt helical conformations. The main results are (i) the
      INDO/S parametrization with rather small excitation manifolds is able to
      reproduce, at low computational costs, the experimental CD spectra of several
      helicenes as well as CD simulations performed at ab initio and time-dependent
      density functional theory level of approximation; (ii) in the series of
      homohelicenes, the rotatory strength of the lowest-energy band increases almost
      linearly with the size of the helix; (iii) as evidenced by the study of
      tetradodecyloxy helicene bisquinone, packing effects can change the sign of
      remarkable CD bands, which are used to assign the structure configuration.

PMID- 18052415
TI  - A density matrix-based method for the linear-scaling calculation of dynamic
      second- and third-order properties at the Hartree-Fock and Kohn-Sham density
      functional theory levels.
AB  - A density matrix-based time-dependent self-consistent field (D-TDSCF) method for
      the calculation of dynamic polarizabilities and first hyperpolarizabilities using
      the Hartree-Fock and Kohn-Sham density functional theory approaches is presented.
      The D-TDSCF method allows us to reduce the asymptotic scaling behavior of the
      computational effort from cubic to linear for systems with a nonvanishing band
      gap. The linear scaling is achieved by combining a density matrix-based
      reformulation of the TDSCF equations with linear-scaling schemes for the
      formation of Fock- or Kohn-Sham-type matrices. In our reformulation only
      potentially linear-scaling matrices enter the formulation and efficient sparse
      algebra routines can be employed. Furthermore, the corresponding formulas for the
      first hyperpolarizabilities are given in terms of zeroth- and first-order one
      particle reduced density matrices according to Wigner's (2n+1) rule. The scaling
      behavior of our method is illustrated for first exemplary calculations with
      systems of up to 1011 atoms and 8899 basis functions.

PMID- 18052416
TI  - Optimization of replica exchange molecular dynamics by fast mimicking.
AB  - We present an approach to mimic replica exchange molecular dynamics simulations
      (REMD) on a microsecond time scale within a few minutes rather than the years,
      which would be required for real REMD. The speed of mimicked REMD makes it a
      useful tool for "testing" the efficiency of different settings for REMD and then
      to select those settings, that give the highest efficiency. We present an
      optimization approach with the example of Hamiltonian REMD using soft-core
      interactions on two model systems, GTP and 8-Br-GTP. The optimization process
      using REMD mimicking is very fast. Optimization of Hamiltonian-REMD settings of
      GTP in explicit water took us less than one week. In our study we focus not only
      on finding the optimal distances between neighboring replicas, but also on
      finding the proper placement of the highest level of softness. In addition we
      suggest different REMD simulation settings at this softness level. We allow
      several replicas to be simulated at the same Hamiltonian simultaneously and
      reduce the frequency of switching attempts between them. This approach allows for
      more efficient conversions from one stable conformation to the other.

PMID- 18052417
TI  - An analytical derivative procedure for the calculation of vibrational Raman
      optical activity spectra.
AB  - We present an analytical time-dependent Hartree-Fock algorithm for the
      calculation of the derivatives of the electric dipole-magnetic dipole
      polarizability with respect to atomic Cartesian coordinates. Combined with
      analogous procedures to determine the derivatives of the electric dipole-electric
      dipole and electric dipole-electric quadrupole polarizabilities, it enables a
      fully analytical evaluation of the three frequency-dependent vibrational Raman
      optical activity (VROA) invariants within the harmonic approximation. The
      procedure employs traditional non-London atomic orbitals, and the gauge-origin
      dependence of the VROA intensities has, therefore, been assessed for the commonly
      used aug-cc-pVDZ and rDPS:3-21G basis sets.

PMID- 18052418
TI  - Automatic generation of potential energy and property surfaces of polyatomic
      molecules in normal coordinates.
AB  - A procedure for the automatic construction of Born-Oppenheimer (BO) potential
      energy and molecular property surfaces in rectilinear normal coordinates is
      presented and its suitability and accuracy when combined with vibrational
      structure calculations are assessed. The procedure relies on a hierarchical n
      mode representation of the BO potential energy or molecular property surface,
      where the n-mode term of the sequence of potentials/molecular properties includes
      only the couplings between n or less vibrational degrees of freedom. Each n-mode
      cut of the energy/molecular property surface is first evaluated in a grid of
      points with ab initio electronic structure methods. The ab initio data are then
      spline interpolated and a subsequent polynomial fitting provides an analytical
      semiglobal representation for use in vibrational structure programs. The
      implementation of the procedure is outlined and the accuracy of the method is
      tested on water and difluoromethane. Strategies for improving the proposed
      algorithm are also discussed.

PMID- 18052419
TI  - A first principles theory of nuclear magnetic resonance J-coupling in solid-state
      systems.
AB  - A method to calculate NMR J-coupling constants from first principles in extended
      systems is presented. It is based on density functional theory and is formulated
      within a planewave-pseudopotential framework. The all-electron properties are
      recovered using the projector augmented wave approach. The method is validated by
      comparison with existing quantum chemical calculations of solution-state systems
      and with experimental data. The approach has also been applied to the
      silicophosphate, Si(5)O(PO(4))(6), giving (31)P-(29)Si-couplings which are in
      excellent agreement with experiment.

PMID- 18052420
TI  - Block correlated coupled cluster theory with a complete active-space self
      consistent-field reference function: the formulation and test applications for
      single bond breaking.
AB  - Block correlated coupled cluster (BCCC) theory with a complete active-space self
      consistent-field (CASSCF) reference function is presented. This theory provides
      an alternative multireference coupled cluster framework to describe the
      multireference characters of the ground-state wave functions. In this approach, a
      multireference block is defined to incorporate the nondynamic correlation, and
      all other blocks involve just a single spin orbital. The cluster operators are
      truncated up to the four-block correlation level, leading to the BCCC4 scheme.
      For a single bond breaking problem, the present CAS-BCCC4 approach with a
      CASSCF(2,2) reference function computationally scales as the traditional single
      reference coupled cluster singles and doubles. We have applied the present
      approach to investigate the electronic structures of several model systems
      including H4, P4, and BeH(2), and the single bond breaking processes in small
      systems such as F(2), HF, BH, and CH(4). A comparison of our results with those
      from full configuration interaction calculations shows that the present approach
      can provide quantitative descriptions for all the studied systems. The size
      consistency error is found to be quite small in the dissociation limit of
      diatomic molecules F(2), HF, and BH.

PMID- 18052421
TI  - Accurate ab initio potential energy curve of F2. II. Core-valence correlations,
      relativistic contributions, and long-range interactions.
AB  - The nonrelativistic, valence-shell-only-correlated ab initio potential energy
      curve of the F(2) molecule, which was reported in the preceding paper, is
      complemented by determining the energy contributions that arise from the electron
      correlations that involve the core electrons as well as the contributions that
      are due to spin-orbit coupling and scalar relativistic effects. The dissociation
      curve rises rather steeply toward the energy of the dissociated atoms because, at
      larger distances, the atomic quadrupole-quadrupole repulsion and spin-orbit
      coupling counteract the attractive contributions from incipient covalent binding
      and correlation forces including dispersion.

PMID- 18052422
TI  - Effect of the Gouy phase on the coherent phase control of chemical reactions.
AB  - We show how the spatial phase of a focused laser beam may be used as a tool for
      controlling the branching ratio of a chemical reaction. Guoy discovered [Acad.
      Sci., Paris, C. R. 110, 1250 (1890)] that when an electromagnetic wave passes
      through a focus its phase increases by pi. In a coherent control scheme involving
      the absorption of n photons of frequency omega(m) and m photons of frequency
      omega(n), the overall phase shift produced by the Gouy phase is (n-m)pi. At any
      given point in space, this phase shift is identical for all reaction products.
      Nevertheless, if the yields for different reaction channels have different
      intensity dependencies, the Gouy phase produces a net phase lag between the
      products that varies with the axial coordinate of the laser focus. We obtain here
      analytical and numerical values of this phase as the laser focus is scanned
      across the diameter of the molecular beam, taking into account the Rayleigh range
      and astigmatism of the laser beam and saturation of the transition. We also show
      that the modulation depth of the interference pattern may be increased by
      optimizing the relative intensities of the two fields.

PMID- 18052423
TI  - Nuclear quadrupole moment of 139La from relativistic electronic structure
      calculations of the electric field gradients in LaF, LaCl, LaBr, and LaI.
AB  - Relativistic coupled cluster theory is used to determine accurate electric field
      gradients in order to provide a theoretical value for the nuclear quadrupole
      moment of (139)La. Here we used the diatomic lanthanum monohalides LaF, LaCl,
      LaBr, and LaI as accurate nuclear quadrupole coupling constants are available
      from rotational spectroscopy by Rubinoff et al. [J. Mol. Spectrosc. 218, 169
      (2003)]. The resulting nuclear quadrupole moment for (139)La (0.200+/-0.006 barn)
      is in excellent agreement with earlier work using atomic hyperfine spectroscopy
      [0.20(1) barn].

PMID- 18052424
TI  - Photodissociation spectroscopy of stored CH+ and CD+ ions: analysis of the b
      3Sigma(-)-a 3Pi system.
AB  - We have measured the photodissociation spectrum of CH(+) and CD(+) molecular
      ions, stored as fast (MeV) ion beams in the heavy-ion storage ring TSR. Several b
      (3)Sigma(-)-a (3)Pi bands were observed as strong resonances because a large
      fraction of the ions in the metastable a (3)Pi(v=0) state were pumped to b
      (3)Sigma(-) levels and predissociated via the c (3)Sigma(+) state into C(+) and
      H(D) fragments. From a rotational analysis of the 2-0, 3-0, and 4-0 bands in
      CH(+) and the 3-0 and 4-0 bands in CD(+), we derive spectroscopic constants for
      these levels and also revise a previous analysis of the 0-0 and 1-0 bands in
      CH(+). Combining all data delivers new, significantly adjusted equilibrium
      constants for the b (3)Sigma(-) and a (3)Pi electronic states. Apart from the
      spectroscopic analysis, we estimate the predissociation rates of the upper b
      (3)Sigma(-) vibrational levels in CH(+) and compare them to a model. For the
      initial rovibrational distribution of the stored metastable CH(+) molecules, the
      data indicate a faster vibrational cooling than derived before, and rotational
      cooling at a rate similar to the X (1)Sigma(+) ground state. New aspects of the
      spin-forbidden a (3)Pi-X (1)Sigma(+) radiative decay are discussed. Finally, we
      predict b (3)Sigma(-)-a (3)Pi absorption and a (3)Pi-X (1)Sigma(+) emission lines
      through which CH(+) in the metastable a (3)Pi(v=0) state might be detectable in
      astrophysical environments.

PMID- 18052425
TI  - Wave packet driven dissociation and concerted elimination in CH2I2.
AB  - We follow the evolution of a vibrational wave packet in a highly excited state of
      the halogenated methane CH(2)I(2). We observe how the wave packet modulates both
      dissociation and concerted elimination to form CH(2)I(+) and I(2) (+),
      respectively. We present a simple and intuitive interpretation of the molecular
      dynamics leading to the formation of the products.

PMID- 18052426
TI  - New insights in the formation of thioxophosphine: a quantum chemical study.
AB  - The investigation of the thioxophosphine (PS) formation from different reaction
      paths is successfully performed and presented in this paper. The PH(3)+SH(1)
      reaction is likely to yield the intermediates PH(2) (2)+H(2)S through an energy
      barrier of 2.8 kcal mol(-1). However, the next step is the H(2)PS(2) formation,
      which has a too high energy barrier, 52.6 kcal mol(-1). The PH(3)+S(1) reaction
      path is the likely source of the HPS(1) molecule. The other possibilities are the
      PH(1)+H(2)S, PH(2) (2)+SH(1), and PH(3)+H(2)S reactions, but they are spin
      forbidden and energetically unfavorable for the HPS(1) and PSH(1) formations. On
      the other hand, the PS(2) formation is more likely to happen by the PH(1)+SH(1)
      reaction. The PH(2) (2)+S(1), PH(3)+SH(1), P(2)+H(2)S, and P(4)+H(2)S reactions
      are also favorable in terms of energetics; however, these reactions are spin
      forbidden. The chemical mechanism for the PS(2) formation is now presented in
      more details, which is of great importance in the atmosphere of Jupiter and
      Saturn, and in interstellar medium.

PMID- 18052427
TI  - The permanent electric dipole moment of chromium monodeuteride, CrD.
AB  - A number of low-N lines of the X (6)Sigma(+)<--A (6)Sigma(+)(0,0) band of
      chromium monodeuteride, CrD, have been recorded at near the natural linewidth
      limit by high resolution laser excitation spectroscopy of a supersonic molecular
      beam sample. The shifts and splitting of these lines caused by a static electric
      field have been analyzed to give the permanent electric dipole moments of the X
      (6)Sigma(+)(upsilon=0) and A (6)Sigma(+)(upsilon=0) states as 3.510(33) and
      1.153(3) D, respectively. The dipole moment of the A (6)Sigma(+)(upsilon=0) state
      can be measured with higher precision because of some interesting near
      degeneracies in its level structure. The trends in the observed dipole moments
      for the first-row transition metal monohydrides are rationalized and compared
      with theoretical predictions.

PMID- 18052428
TI  - Reinvestigation of the electronic spectroscopy of the Au-Ar complex.
AB  - The Au-Ar complex is reinvestigated employing resonance-enhanced multiphoton
      ionization spectroscopy. Spectra are reported, corresponding to the atomic
      transition Au(6p<--6s). This electronic excitation yields (2)Pi and (2)Sigma(+)
      states of Au-Ar, which interact under the influence of spin-orbit coupling. The
      spectra are consistent with strong sigma-pi mixing induced by the large spin
      orbit coupling of Au, leading to strong interaction of the two Omega=12 states,
      which arise from the Ar((1)S(0))+Au((2)P(12,32)) asymptotes, and the consequent
      formation of a "shelf" on the outer wall of the lowest Omega=12 state. In
      addition, high-level ab initio calculations are reported on the ground electronic
      state, X (2)Sigma(+), including extrapolation to the basis set limit.

PMID- 18052429
TI  - Temperature and heat capacity of atomic clusters as estimated in terms of kinetic
      energy release of atomic evaporation.
AB  - The temperature and heat capacity of isolated atomic clusters are studied in
      terms of an ab initio statistical theory of kinetic energy distribution by atomic
      evaporation. Two definitions of canonical temperature are examined and
      numerically compared: One is based on the most probable kinetic energy release
      (KER), whereas the other is determined with use of the entire distribution of the
      KER. The mutual relationship and their advantages are discussed.

PMID- 18052430
TI  - An experimental and theoretical study of the S(1)<--S0 transition of p
      ethynyltoluene.
AB  - The one photon and the two photon S(1)<--S(0) spectra of jet-cooled p
      ethynyltoluene have been measured for the first time, and a detailed vibronic
      analysis for both spectra has been attained. Mass analyzed resonance enhanced
      multiphoton ionization spectroscopy is the employed technique. In the one photon
      spectrum, the allowed component (origin and Franck-Condon bands) is much weaker
      than the forbidden component, and the same mechanisms as in the one photon
      spectrum of phenylacetylene are observed. The methyl torsional transitions are
      active. The 0(0) (0) band is at 35 483 cm(-1). The two photon spectrum is very
      strong and bears a resemblance to the two photon spectrum of phenylacetylene. The
      potential barrier of the methyl rotor in the S(1) state has been determined as
      V(6)=-12 cm(-1) with B(CH(3) )=5.55 cm(-1). Ab initio calculations, MP2(full)/cc
      pVTZ and CAS/cc-pVTZ, have been implemented for the geometry optimization and the
      normal mode vibration computation in the S(0) and S(1) states.

PMID- 18052431
TI  - Coriolis coupling effects on the initial-state-resolved dynamics of the N(2D)+H2-
      >NH+H reaction.
AB  - We present Coriolis coupling effects on the initial-state-resolved dynamics of
      the insertion reaction N((2)D)+H(2)(X (1)Sigma(g) (+))-->NH(X (3)Sigma(-) and a
      (1)Delta)+H((2)S), without and with nonadiabatic Renner-Teller (RT) interactions
      between the NH(2) X (2)B(1) and A (2)A(1) electronic states. We report coupled
      channel (CC) Hamiltonian matrix elements, which take into account both Coriolis
      and RT couplings, use the real wave-packet and flux methods for calculating
      initial-state-resolved reaction probabilities, and contrast CC with centrifugal
      sudden (CS) results. Without RT interactions, Coriolis effects are rather small
      up to J=40, and the CS approximation can be safely employed for calculating
      initial-state-resolved, integral cross sections. On the other hand, RT effects
      are associated with rather large Coriolis couplings, mainly near the linearity of
      NH(2), and the accuracy of the CS approximation thus breaks down at high
      collision energies, when the reaction starts on the excited A (2)A(1) surface. We
      also present the CC-RT distribution of the X (3)Sigma(-) and a (1)Delta
      electronic states of the NH products.

PMID- 18052432
TI  - Evidence for cluster shape effects on the kinetic energy spectrum in thermionic
      emission.
AB  - Experimental kinetic energy release distributions obtained for the thermionic
      emission from C(n) (-) clusters, 10< or =n< or =20, exhibit significant non
      Boltzmann variations. Using phase space theory, these different features are
      analyzed and interpreted as the consequence of contrasting shapes in the daughter
      clusters; linear and nonlinear isomers have clearly distinct signatures. These
      results provide a novel indirect structural probe for atomic clusters associated
      with their thermionic emission spectra.

PMID- 18052433
TI  - Accurate ab initio potential energy curve of F2. III. The vibration rotation
      spectrum.
AB  - An analytical expression is found for the accurate ab initio potential energy
      curve of the fluorine molecule that has been determined in the preceding two
      papers. With it, the vibrational and rotational energy levels of F(2) are
      calculated using the discrete variable representation. The comparison of this
      theoretical spectrum with the experimental spectrum, which had been measured
      earlier using high-resolution electronic spectroscopy, yields a mean absolute
      deviation of about 5 cm(-1) over the 22 levels. The dissociation energy with
      respect to the lowest vibrational energy is calculated within 30 cm(-1) of the
      experimental value of 12 953+/-8 cm(-1). The reported agreement of the
      theoretical spectrum and dissociation energy with experiment is contingent upon
      the inclusion of the effects of core-generated electron correlation, spin-orbit
      coupling, and scalar relativity. The Dunham analysis [Phys. Rev. 41, 721 (1932)]
      of the spectrum is found to be very accurate. New values are given for the
      spectroscopic constants.

PMID- 18052434
TI  - Quantum optimal control of electron ring currents in chiral aromatic molecules.
AB  - We report the results of optimal control simulations of pi-electron rotation
      (ring current) in a six-membered chiral aromatic molecule, 2,5
      dichloro[n](3,6)pyrazinophane (DCP), attached at a surface and excited by a
      linearly polarized UV laser. DCP has a pair of optically allowed, quasidegenerate
      pi-electronic excited states. The laser pulse to generate an approximate angular
      momentum eigenstate consisting of the quasidegenerate states was designed using
      the global optimal control theory. For both counterclockwise and clockwise pi
      electron rotations, the calculated objective functional and target yield as a
      function of the angle of the photon polarization vector show two maxima and two
      minima. The origin of the two minima is coherent excitation to only one of the
      quasidegenerate states. The two maxima arise from creation of a superposition of
      the quasidegenerate states. The optimal control pulse at the maxima is a two
      color laser field resonant with the quasidegenerate states. The electric field of
      the optimal control pulse consists of two parts: a slowly oscillating part with
      phase phi(env) and a rapidly oscillating one. The phase phi(env) is a crucial
      parameter for determination of the rotation direction of pi electrons at the end
      of control. The results of the optimal control simulations suggest that pi
      electron rotation can be controlled by applying a two-color laser field with
      adjusted phases.

PMID- 18052435
TI  - Microwave spectra of O(2)-HF and O(2)-DF: hyperfine interactions and global
      fitting with infrared data.
AB  - Spectra of the open shell complexes O(2)-HF and O(2)-DF were recorded using
      Fourier transform microwave spectroscopy. A complete analysis of the hyperfine
      structure and a global fit including microwave and infrared frequencies [W. M.
      Fawzy, C. M. Lovejoy, D. J. Nesbitt, and J. T. Hougen, J. Chem. Phys. 117, 693
      (2002)] are reported. The Fermi contact interaction between the electron and
      nuclear spins, the electron spin-nuclear spin dipolar interaction, the nuclear
      spin-nuclear spin dipolar interaction, and the nuclear electric quadrupole
      interaction (for O(2)-DF) were considered in the analysis. The correspondence
      between the magnetic hyperfine constants and the two nuclei of the H(D)F is
      unambiguously established. In both O(2)-HF and O(2)-DF, the Fermi contact
      parameter is larger for the fluorine than for the hydrogen, while for the nuclear
      spin-electron spin dipolar hyperfine constants, the reverse is true. The
      effective angle between the HF bond and the a axis of the complex, determined
      from the nuclear spin-nuclear spin interaction constant, is 38(4) degrees. The
      same angle for the DF complex, derived from the deuterium nuclear quadrupole
      coupling constant, is 31(4) degrees.

PMID- 18052436
TI  - Observation of slow charge redistribution preceding excited-state proton
      transfer.
AB  - The photoacid 8-hydroxy-N,N,N',N',N',N'-hexamethylpyrene-1,3,6-trisulfonamide
      (HPTA) and related compounds are used to investigate the steps involved in
      excited-state deprotonation in polar solvents using pump-probe spectroscopy and
      time correlated single photon counting fluorescence spectroscopy. The dynamics
      show a clear two-step process leading to excited-state proton transfer. The first
      step after electronic excitation is charge redistribution occurring on a tens of
      picoseconds time scale followed by proton transfer on a nanosecond time scale.
      The three states observed in the experiments (initial excited state, charge
      redistributed state, and proton transfer state) are recognized by distinct
      features in the time dependence of the pump-probe spectrum and fluorescence
      spectra. In the charge redistributed state, charge density has transferred from
      the hydroxyl oxygen to the pyrene ring, but the OH sigma bond is still intact.
      The experiments indicate that the charge redistribution step is controlled by a
      specific hydrogen bond donation from HPTA to the accepting base molecule. The
      second step is the full deprotonation of the photoacid. The full deprotonation is
      clearly marked by the growth of stimulated emission spectral band in the pump
      probe spectrum that is identical to the fluorescence spectrum of the anion.

PMID- 18052437
TI  - Multiconfigurational self-consistent field and multireference internally
      contracted configuration interaction studies on the excited states of weakly
      bonded NO2 dimer (N2O4).
AB  - In this paper, the vertical excitation energies of total of 32 states of N(2)O(4)
      including the lowest two singlet states and two triplet states of each of the
      A(g), B(3u), B(2u), B(1g), B(1u), B(2g), B(3g), and A(u) symmetries were
      calculated at multiconfigurational self-consistent field (MCSCF) and the
      multireference internally contracted configuration interaction (MRCI) levels of
      theory on the active space (15o,16e) with aug-cc-pVDZ basis set. The potential
      energy curves of the eight singlet states(1 (1)A(g), 1 (1)B(3u), 1 (1)B(2u), 1
      (1)B(1g), 1 (1)B(1u), 1 (1)B(2g), 1 (1)B(3g), and 1 (1)A(u)) and eight triplet
      states (1 (3)A(g), 1 (3)B(3u), 1 (3)B(2u), 1 (3)B(1g), 1 (3)B(1u), 1 (3)B(2g), 1
      (3)B(3g), and 1 (3)A(u)) were calculated at MCSCF and MRCI levels of theory on
      the active space (15o,16e) with aug-cc-pVDZ basis set along the N-N distance. The
      vertical excitation energies of 1 (1)B(3u), 1 (1)B(2u), and 1 (1)B(1u) states
      with nonzero transition moment are 4.60 eV (269.6 nm), 6.06 eV (204.6 nm), and
      7.71 eV (160.8 nm), respectively, at MRCI level of theory. The photodissociation
      asymptotics were assigned as NO(2)(X (2)A(1))+NO(2)(X (2)A(1)) for ground state 1
      (1)A(g) and the 1 (3)B(1u) state, NO(2)(X (2)A(1))+NO(2)(1 (2)A(2)) for the 1
      (1)B(1g), 1 (3)B(1g), 1 (1)A(u), and 1 (3)A(u) states, NO(2)(X (2)A(1))+NO(2)(1
      (2)B(1)) for the 1 (1)B(3u), 1 (3)B(3u), 1 (1)B(2g), and 1 (3)B(2g) states, and
      NO(2)(X (2)A(1))+NO(2)(1 (2)B(2)) for the 1 (1)B(2u), 1 (3)B(2u), 1 (1)B(3g), and
      1 (3)B(3g) states.

PMID- 18052438
TI  - Doped liquid nitrobenzene is ferroelectric.
AB  - The high resolution hyper-Rayleigh light scattering spectrum for liquid
      nitrobenzene doped with triflic acid (CF(3)SO(3)H) shows a narrow spike at zero
      frequency shift which has the polarization signature of a polar longitudinal
      collective mode. This spectral spike disappears for pure nitrobenzene. The
      spectral spike is interpreted as due to ferroelectric domains in the liquid. The
      dopant molecules appear to induce ferroelectric organization of the nitrobenzene
      molecules which is otherwise absent in the pure liquid. Estimated domain size is
      34 nm and relaxation time is 50 ns.

PMID- 18052439
TI  - Operator-based triple-mode Floquet theory in solid-state NMR.
AB  - Many solid-state NMR experiments exploit interference effects between time
      dependencies in the system Hamiltonian to design an effective time-independent
      Hamiltonian with the desired properties. Effective Hamiltonians can be designed
      such that they contain only selected parts of the full system Hamiltonian while
      all other parts are averaged to zero. A general theoretical description of such
      experiments has to accommodate several time-dependent perturbations with
      incommensurate frequencies. We describe an extension of the analytical operator
      based Floquet description of NMR experiments to situations with three
      incommensurate frequencies. Experiments with three time dependencies are quite
      common in solid-state NMR. Examples include experiments which combine magic-angle
      spinning and radio-frequency irradiation on two nuclei or asynchronous multiple
      pulse sequences on a single spin species. The Floquet description is general in
      the sense that the resulting effective Hamiltonians can be calculated without a
      detailed knowledge of the spin-system Hamiltonian and can be expressed fully as a
      function of the Fourier components of the time-dependent Hamiltonian. As a
      prototype experiment we treat the application of two continuous-wave (cw) radio
      frequency fields under magic-angle spinning. Experiments that are included in
      such a description are Hartmann-Hahn cross polarization or rotary-resonance
      recoupling experiments with simultaneous cw decoupling.

PMID- 18052440
TI  - Viscous fingering in a horizontal flow through a porous medium induced by
      chemical reactions under isothermal and adiabatic conditions.
AB  - In this work we analyze the viscous fingering instability induced by an
      autocatalytic chemical reaction in a liquid flowing horizontally through a porous
      medium. We have analyzed the behavior of the system for isothermal as well as
      adiabatic conditions. The kinetics of the reaction is chosen so that the rate
      depends on the concentration of only a single species. Since the reaction is
      autocatalytic the system admits a traveling wave solution. For endothermic
      reactions the concentration wave and temperature wave are mirror images, whereas
      for an exothermic reaction they are similar or parallel. The viscosity of the
      fluid is assumed to depend strongly on the concentration of the product and
      temperature of the medium. The dependence of viscosity on concentration (decrease
      with concentration) can destabilize the traveling wave resulting in the formation
      of viscous fingers. We have performed a linear stability analysis to determine
      the stability of the base traveling wave solution. The stability predictions have
      been confirmed by nonlinear simulations of the governing equations based on a
      finite difference scheme. We observe that including the temperature dependency of
      viscosity stabilizes the flow for an endothermic reaction, i.e., regions which
      exhibited viscous fingering now demonstrate stable displacement. For exothermic
      systems, however, the system exhibits less stable behavior under adiabatic
      conditions, i.e., it is destabilized by both concentration and temperature
      dependencies of viscosity.

PMID- 18052441
TI  - Equivalence of nonequilibrium algorithms for simulations of planar Couette flow
      in confined fluids.
AB  - Shear flow in fluids confined between planar solid walls is conventionally
      simulated by moving the walls past each other at constant relative velocity. In
      infinite fluids (in periodic boundary conditions), it is simulated using one of
      the "synthetic" nonequilibrium algorithms (the so-called Sllod and Dolls
      algorithms). Here I formulate the boundary conditions for the motion of confining
      walls that make these three algorithms equivalent in the weak-field limit.

PMID- 18052442
TI  - Mesoscopic nanoshells: geometry-dependent plasmon resonances beyond the
      quasistatic limit.
AB  - The plasmon response of a spherical metallic shell becomes significantly more
      complex as its size is increased beyond the quasistatic limit. With increasing
      size and decreasing aspect ratio (r1/r2), higher order multipolar modes
      contribute in a more dominant manner, and two distinct core-shell geometries
      exist that provide the same dipole plasmon resonance, with differing relative
      multipolar contributions in their overall spectral response. With further
      increase in particle size, the geometric tunability of the core-shell structure
      disappears, and in the infinite radius limit the plasmon response is consistent
      with that of a thin metallic film.

PMID- 18052443
TI  - Development of a classical force field for the oxidized Si surface: application
      to hydrophilic wafer bonding.
AB  - We have developed a classical two- and three-body interaction potential to
      simulate the hydroxylated, natively oxidized Si surface in contact with water
      solutions, based on the combination and extension of the Stillinger-Weber
      potential and of a potential originally developed to simulate SiO(2) polymorphs.
      The potential parameters are chosen to reproduce the structure, charge
      distribution, tensile surface stress, and interactions with single water
      molecules of a natively oxidized Si surface model previously obtained by means of
      accurate density functional theory simulations. We have applied the potential to
      the case of hydrophilic silicon wafer bonding at room temperature, revealing
      maximum room temperature work of adhesion values for natively oxidized and
      amorphous silica surfaces of 97 and 90 mJm(2), respectively, at a water
      adsorption coverage of approximately 1 ML. The difference arises from the
      stronger interaction of the natively oxidized surface with liquid water,
      resulting in a higher heat of immersion (203 vs 166 mJm(2)), and may be explained
      in terms of the more pronounced water structuring close to the surface in
      alternating layers of larger and smaller densities with respect to the liquid
      bulk. The computed force-displacement bonding curves may be a useful input for
      cohesive zone models where both the topographic details of the surfaces and the
      dependence of the attractive force on the initial surface separation and wetting
      can be taken into account.

PMID- 18052445
TI  - Theory of capillary-induced interactions beyond the superposition approximation.
AB  - Within a general theoretical framework, we study the effective, deformation
      induced interaction between two colloidal particles trapped at a fluid interface
      in the regime of small deformations. In many studies, this interaction has been
      computed with the ansatz that the actual interface configuration for the pair is
      given by the linear superposition of the interface deformations around the single
      particles. Here, we assess the validity of this approach and compute the leading
      term of the effective interaction for a large interparticle separation beyond
      this so-called superposition approximation. As an application, we consider the
      experimentally relevant case of interface deformations owing to the electrostatic
      field emanating from charged colloidal particles. In mechanical isolation, i.e.,
      if the net force acting on the total system consisting of the particles plus the
      interface vanishes, the superposition approximation is actually invalid. The
      effective capillary interaction is governed by contributions beyond this
      approximation and turns out to be attractive. For sufficiently small surface
      charges on the colloids, such that linearization is strictly valid, and at
      asymptotically large separations, the effective interaction does not overcome the
      direct electrostatic repulsion between the colloidal particles.

PMID- 18052444
TI  - Structural characterization study of FeCo alloy nanoparticles in a highly porous
      aerogel silica matrix.
AB  - A series of FeCo-SiO(2) nanocomposite aerogels having different FeCo loadings of
      3, 5, and 8 wt % were prepared using a novel urea-assisted sol-gel route. The
      size of the nanoparticles, which was estimated using Scherrer analysis of the
      main peak of the x-ray diffraction pattern, varies from 3 to 8 nm. X-ray
      absorption fine structure (EXAFS) and x-ray absorption near edge structure
      (XANES) techniques at both Fe and Co K edges were used to investigate the
      structure of the FeCo nanoparticles. EXAFS and XANES show that FeCo nanoparticles
      have the typical bcc structure. Evidence of oxidation was observed in low FeCo
      content aerogels. Spatially resolved electron energy loss spectroscopy analysis
      suggests the formation of a passivation layer of predominantly iron oxide.

PMID- 18052446
TI  - Effects of bulk impurity concentration on the reactivity of metal surface:
      sticking of hydrogen molecules and atoms to polycrystalline Nb containing oxygen.
AB  - Nonmetallic impurities segregated onto metal surfaces are able to drastically
      decrease the chemical reactivity of metals. In the present paper, effects of bulk
      impurities on the reactivity of metallic surfaces were investigated in a wide
      temperature range on an example of the sticking of hydrogen molecules and atoms
      to Nb [polycrystalline, with mainly (100)] containing solute oxygen. At all the
      investigated surface temperatures, T(S) (300-1400 K), we found the bulk oxygen
      concentration C(O) to have a strong effect on the integral probability,
      alpha(H(2) ), of dissociative sticking of H(2) molecules followed by hydrogen
      solution in the metal lattice: alpha(H(2) ) monotonically decreased by orders of
      magnitude with increasing C(O) from 0.03 to 1.5 at. %. The sticking coefficient
      alpha(H(2) ) was found to depend on T(S) but not on the gas temperature. The
      effect of C(O) on alpha(H(2) ) is explained by the presence of oxygen-free sites
      (holes in coverage) serving as active centers of the surface reaction in the
      oxygen monolayer upon Nb. In contrast to H(2) molecules, H atoms were found to
      stick to, and be dissolved in, oxygen-covered Nb with a probability comparable to
      1, depending neither on C(O) nor on T(S). This proves that, unlike H(2)
      molecules, H atoms do stick to be dissolved mainly through regular surface sites
      covered by oxygen and not through the holes in coverage.

PMID- 18052447
TI  - Enhanced creation of dispersive monolayer phonons in XePt(111) by inelastic
      helium atom scattering at low energies.
AB  - Conditions likely to lead to enhanced inelastic atomic scattering that creates
      shear horizontal (SH) and longitudinal acoustic (LA) monolayer phonons are
      identified, specifically examining the inelastic scattering of (4)He atoms by a
      monolayer solid of XePt(111) at incident energies of 2-25 meV. There is strong
      inelastic scattering for both dispersive phonon branches (SH and LA) of the
      monolayer at incident energies below 8 meV. Several improvements enable more
      complete wave packet calculations of the inelastic scattering than in previous
      work. Long propagation times are made feasible by adding an absorbing potential
      at large distance. The times now extend to beyond 100 ps and enable a
      clarification of processes involving transient trapping of the He atoms. The wave
      packet is made more monochromatic by significantly increasing the spatial width
      of the initial Gaussian shape. The narrower energy distribution in the incident
      beam then enables a demonstration of strong energy dependence of the scattering
      over a scale of less than 0.3 meV.

PMID- 18052448
TI  - A simple model of molecular electronic devices and its analytical solution.
AB  - I present an analytically solvable model for molecular electronic devices (MEDs).
      The model contains all the essential components: semi-infinite contacts, molecule
      contact interface, and of course, the molecule. I obtain explicit expression for
      the reflection coefficient r(E), as well as for the transmission probability T(E)
      [T(E)=1-mid R:r(E)mid R:(2)]. r(E) exhibits a surprisingly simple structure if
      studied as a function of a complex energy variable E. In this case, r(E) can be
      expressed in terms of a finite number of eigenvalues of a non-Hermitian
      Hamiltonian. This Hamiltonian also yields the molecular part of the MED wave
      function. Considering various MEDs, it is illustrated that the theory presented
      allows for a transparent interpretation of molecular conductance in terms of
      discrete eigenstates.

PMID- 18052449
TI  - Sum frequency generation surface spectra of ice, water, and acid solution
      investigated by an exciton model.
AB  - A new computational scheme is presented for calculation of sum frequency
      generation (SFG) spectra, based on the exciton model for OH bonds. The scheme is
      applied to unified analysis of the SFG spectra in the OH-stretch region of the
      surfaces of ice, liquid water, and acid solution. A significant role of
      intermolecularly coupled collective modes is pointed out. SFG intensity
      amplification observed for acid solutions in the H-bonded OH-stretch region is
      reproduced qualitatively and accounted for by enhanced orientational preference
      "into the surface" of the H(2)O bisectors within the hydronium solvation shell.

PMID- 18052450
TI  - Scattering form factors for self-assembled network junctions.
AB  - The equilibrium microstructures in microemulsions and other self-assembled
      systems show complex, connected shapes such as symmetric bicontinuous spongelike
      structures and asymmetric bicontinuous networks formed by cylinders
      interconnected at junctions. In microemulsions, these cylinder network
      microstructures may mediate the structural transition from a spherical or
      globular phase to the bicontinuous microstructure. To understand the structural
      and statistical properties of such cylinder network microstructures as measured
      by scattering experiments, models are needed to extract the real-space structure
      from the scattering data. In this paper, we calculate the scattering functions
      appropriate for cylinder network microstructures. We focus on such networks that
      contain a high density of network junctions that connect the cylindrical
      elements. In this limit, the network microstructure can be regarded as an
      assembly of randomly oriented, closed packed network junctions (i.e., the
      cylinder scattering contributions are neglected). Accordingly, the scattering
      spectrum of the network microstructure can be calculated as the product of the
      junction number density, the junction form factor, which describes the scattering
      from the surface of a single junction, and a structure factor, which describes
      the local correlations of different junctions due to junction interactions
      (including their excluded volume). This approach is applied to analyze the
      scattering data from a bicontinuous microemulsion with equal volumes of water and
      oil. In a second approach, we included the cylinder scattering contribution in
      the junction form factor by calculating the scattering intensity of Y junctions
      to which three rods with spherical cross section are attached. The respective
      theoretical predictions are compared with results of neutron scattering
      measurements on a water-in-oil microemulsion with a connected microstructure.

PMID- 18052451
TI  - Solute rotational dynamics at the water liquid/vapor interface.
AB  - The rotational dynamics of a number of diatomic molecules adsorbed at different
      locations at the interface between water and its own vapors are studied using
      classical molecular dynamics computer simulations. Both equilibrium orientational
      and energy correlations and nonequilibrium orientational and energy relaxation
      correlations are calculated. By varying the dipole moment of the molecule and its
      location, and by comparing the results with those in bulk water, the effects of
      dielectric and mechanical frictions on reorientation dynamics and on rotational
      energy relaxation can be studied. It is shown that for nonpolar and weekly polar
      solutes, the equilibrium orientational relaxation is much slower in the bulk than
      at the interface. As the solute becomes more polar, the rotation slows down and
      the surface and bulk dynamics become similar. The energy relaxation (both
      equilibrium and nonequilibrium) has the opposite trend with the solute dipole
      (larger dipoles relax faster), but here again the bulk and surface results
      converge as the solute dipole is increased. It is shown that these behaviors
      correlate with the peak value of the solvent-solute radial distribution function,
      which demonstrates the importance of the first hydration shell structure in
      determining the rotational dynamics and dependence of these dynamics on the
      solute dipole and location.

PMID- 18052452
TI  - Characterization of porosity in vapor-deposited amorphous solid water from
      methane adsorption.
AB  - We have characterized the porosity of vapor-deposited amorphous solid water (ice)
      films deposited at 30-40 K using several complementary techniques such as quartz
      crystal microgravimetry, UV-visible interferometry, and infrared reflectance
      spectrometry in tandem with methane adsorption. The results, inferred from the
      gas adsorption isotherms, reveal the existence of microporosity in all vapor
      deposited films condensed from both diffuse and collimated water vapor sources.
      Films deposited from a diffuse source show a step in the isotherms and much less
      adsorption at low pressures than films deposited from a collimated source with
      the difference increasing with film thickness. Ice films deposited from a
      collimated vapor source at 77 degrees incidence are mesoporous, in addition to
      having micropores. Remarkably, mesoporosity is retained upon warming to
      temperatures as high as 140 K where the ice crystallized. The binding energy
      distribution for methane adsorption in the micropores of ice films deposited from
      a collimated source peaks at approximately 0.083 eV for deposition at normal
      incidence and at approximately 0.077 eV for deposition at >45 degrees incidence.
      For microporous ice, the intensity of the infrared bands due to methane molecules
      on dangling OH bonds on pore surfaces increases linearly with methane uptake, up
      to saturation adsorption. This shows that the multilayer condensation of methane
      does not occur inside the micropores. Rather, filling of the core volume results
      from coating the pore walls with the first layer of methane, indicating pore
      widths below a few molecular diameters. For ice deposited at 77 degrees
      incidence, the increase in intensity of the dangling bond absorptions modified by
      methane adsorption departs from linearity at large uptakes.

PMID- 18052453
TI  - Translation and reorientation of CD4 molecules in nanoscale cages of zeolites as
      studied by deuteron spin-lattice relaxation.
AB  - Deuteron spin-lattice relaxation was applied to study translational and
      rotational mobility of CD(4) molecules trapped in the cages of zeolites.
      Tetrahedral methane molecules are treated as quantum rotators. Relaxation rates
      related to the intraquadrupole interaction are derived for the T and A+E symmetry
      species in the presence of large tunneling splittings, consistently with the
      assumption that A and E species molecules relax at the same rate. An exchange
      model is presented, which describes the effect on relaxation of CD(4) jumping
      between two positions characterized by different potentials. While staying at
      either position bonded to an atom or ion at the cage wall, the molecule has some
      freedom to move in the vicinity. This causes a time-dependent external electric
      field gradient, which contributes to the deuteron relaxation rate via the
      electric quadrupole interaction. Spin conversion transitions couple the
      relaxation of magnetizations M(T) and M(AE), which is taken into account by
      reapplying the presented model under somewhat different conditions. Such a two
      step procedure leads to successful fits with the experimental results obtained in
      the range of temperatures roughly 20-200 K for zeolites HY, NaA, and NaMordenite.
      At higher temperatures CD(4) molecules fly freely across zeolite cages and
      relaxation changes accordingly, while incoherent tunneling dominates for immobile
      molecules below 20 K.

PMID- 18052457
TI  - Perspective: "An improved double-toroidal spectrometer for gas phase (e,2e)
      studies" [Rev. Sci. Instrum. 78, 111301 (2007)].

PMID- 18052454
TI  - Dynamics of proteins: light scattering study of dilute and dense colloidal
      suspensions of eye lens homogenates.
AB  - We report a dynamic light scattering study on protein suspensions of bovine lens
      homogenates at conditions (pH and ionic strength) similar to the physiological
      ones. Light scattering data were collected at two temperatures, 20 and 37 degrees
      C, over a wide range of concentrations from the very dilute limit up to the dense
      regime approaching the physiological lens concentration. A comparison with
      experimental data from intact bovine lenses was advanced, revealing differences
      between dispersions and lenses at similar concentrations. In the dilute regime,
      two scattering entities were detected and identified with the long-time self
      diffusion modes of alpha-crystallins and their aggregates, which naturally exist
      in lens nucleus. Upon increasing protein concentration, significant changes in
      time correlation function were observed starting at approximately 75 mg ml(-1),
      where a new mode originating from collective diffusive motions becomes visible.
      Self-diffusion coefficients are temperature insensitive, whereas the collective
      diffusion coefficient depends strongly on temperature revealing a reduction of
      the net repulsive interparticle forces with decreasing temperature. While there
      are no rigorous theoretical approaches on particle diffusion properties for
      multicomponent, nonideal hard sphere polydispersed systems, as the suspensions
      studied here, a discussion of the volume fraction dependence of the long-time
      self-diffusion coefficient in the context of existing theoretical approaches was
      undertaken. This study is purported to provide some insight into the complex
      light scattering pattern of intact lenses and the interactions between the
      constituent proteins that are responsible for lens transparency. This would lead
      to understand basic mechanisms of specific protein interactions that lead to lens
      opacification (cataract) under pathological conditions.

PMID- 18052458
TI  - Invited article: an improved double-toroidal spectrometer for gas phase (e,2e)
      studies.
AB  - A new spectrometer is described for measuring the momentum distributions of
      scattered electrons arising from electron-atom and electron-molecule ionization
      experiments. It incorporates and builds on elements from a number of previous
      designs, namely, a source of polarized electrons and two high-efficiency
      electrostatic electron energy analyzers. The analyzers each comprise a seven
      element retarding-electrostatic lens system, four toroidal-sector electrodes, and
      a fast position-and-time-sensitive two-dimensional delay-line detector. Results
      are presented for the electron-impact-induced ionization of helium and the
      elastic scattering of electrons from argon and helium which demonstrate that high
      levels of momentum resolution and data-collection efficiency are achieved.
      Problematic aspects regarding variations in collection efficiency over the
      accepted momentum phase space are addressed and a methodology for their
      correction presented. Principles behind the present design and previous designs
      for electrostatic analyzers based around electrodes of toroidal-sector geometry
      are discussed and a framework is provided for optimizing future devices.

PMID- 18052459
TI  - An atomic jet in a heat pipe for multiphoton spectroscopy.
AB  - A conventional heat pipe is modified to operate as a novel atomic jet setup with
      unprecedented advantages for multiphoton spectroscopy of alkaline-earth atoms
      especially to study the effect of external electric field, controlled excitation
      of forbidden transitions and for the study of collisional broadening and shift of
      excited states, and time evolution of Rydberg atoms.

PMID- 18052460
TI  - Common-path optical coherence tomography with side-viewing bare fiber probe for
      endoscopic optical coherence tomography.
AB  - All-fiber-optic common-path optical coherence tomography (OCT) using a side
      viewing bare fiber probe has been demonstrated and analyzed. A bare single mode
      fiber tip is angle cleaved at approximately 49 degrees to enable side
      illumination due to total internal reflection. The bare fiber probe was inserted
      in an arterial tissue and a circumferential OCT scan was obtained. The research
      is aimed at realizing highly miniaturized monolithic probes for possible
      applications in miniature endoscopic OCT or intravascular OCT. The effects of the
      angle of the cleaved fiber on reference reflection and the sensitivity of the
      common-path OCT system have been studied theoretically. The angle cleaved fiber
      probe is also used in series with a microlens to analyze and optimize its
      performance in a common-path OCT system. Our research aims to explore the
      combined advantages of common-path OCT and extremely simplified miniature probe
      design and to discuss how it may greatly simplify the endoscopic OCT
      instrumentation eventually.

PMID- 18052461
TI  - A diffraction-compensating 0-25 ns free space terahertz delay line for coherent
      quantum control.
AB  - Free space delay lines provide pulses of variable time spacing for optical
      experiments such as pump-probe spectroscopy and coherent quantum control,
      including spin and photon echo techniques. However, in the terahertz region of
      the spectrum, beam divergence due to diffraction limits the useful length of
      traditional free space delay lines. We present a novel double-folded variable
      delay line for light in the frequency range 0.24-1.2 THz, which incorporates a
      symmetric arrangement of lenses whose spacing can be adjusted to compensate for
      diffraction at each delay. Scalable for use in other wavelength regimes, the
      design relays an input Gaussian beam waist to the output with up to 25 ns (
      approximately 8 m) total delay and is enclosed in a desiccated volume of <0.5 m3.
      The delay line can deliver two or three pulses with relative amplitudes
      controlled via variable spacing silicon etalon beam splitters. Profiles of a 0.24
      THz beam show good agreement with calculations at long delays, with insertion
      loss per delay stage of approximately 3 dB.

PMID- 18052462
TI  - High repetition rate laser produced soft x-ray source for ultrafast x-ray
      absorption near edge structure measurements.
AB  - Recent progress in high intensity ultrafast laser systems provides the
      opportunity to produce laser plasma x-ray sources exhibiting broad spectrum and
      high average x-ray flux that are well adapted to x-ray absorption measurements.
      In this paper, the development of a laser based x-ray absorption near edge
      structure (XANES) beamline exhibiting high repetition rate by using the Advanced
      Laser Light Source (ALLS) facility 100 Hz laser system (100 mJ, 35 fs at 800 nm)
      is presented. This system is based on a broadband tantalum solid target soft x
      ray source and a grazing incidence grating spectrometer in the 1-5 nm wavelength
      range. To demonstrate the high potential of this laser based XANES technique in
      condensed matter physics, material science, or biology, measurements realized
      with several samples are presented: VO2 vanadium L edge, Si3N4 nitrogen K edge,
      and BPDA/PPD polyimide carbon K edge. The characteristics of this laser based
      beamline are discussed in terms of brightness, signal to noise ratio, and
      compared to conventional synchrotron broadband x-ray sources which allow
      achieving similar measurements. Apart from the very compact size and the relative
      low cost, the main advantages of such a laser based soft x-ray source are the
      picosecond pulse duration and the perfect synchronization between this x-ray
      probe and a laser pulse excitation which open the way to the realization of time
      resolved x-ray absorption measurements with picosecond range time resolution to
      study the dynamics of ultrafast processes and phase transition.

PMID- 18052463
TI  - IMPACT: a facility to study the interaction of low-energy intense particle beams
      with dynamic heterogeneous surfaces.
AB  - The Interaction of Materials with Particles and Components Testing (IMPACT)
      experimental facility is furnished with multiple ion sources and in situ
      diagnostics to study the modification of surfaces undergoing physical, chemical,
      and electronic changes during exposure to energetic particle beams. Ion beams
      with energies in the range between 20 and 5000 eV can bombard samples at flux
      levels in the range of 10(10)-10(15) cm(-2) s(-1); parameters such as ion angle
      of incidence and exposed area are also controllable during the experiment. IMPACT
      has diagnostics that allow full characterization of the beam, including a Faraday
      cup, a beam imaging system, and a retarding field energy analyzer. IMPACT is
      equipped with multiple diagnostics, such as electron (Auger, photoelectron) and
      ion scattering spectroscopies that allow different probing depths of the sample
      to monitor compositional changes in multicomponent and/or layered targets. A
      unique real-time erosion diagnostic based on a dual quartz crystal microbalance
      measures deposition from an eroding surface with rates smaller than 0.01 nm/s,
      which can be converted to a sputter yield measurement. The monitoring crystal can
      be rotated and placed in the target position so that the deposited material on
      the quartz crystal oscillator surface can be characterized without transfer
      outside of the vacuum chamber.

PMID- 18052464
TI  - Four-point bisensitivity velocity interferometer with a multireflection etalon.
AB  - A four-point bisensitivity velocity interferometer system for any reflector
      (VISAR) with a renovative delay etalon is proposed and demonstrated. In this
      interferometer, we introduce a new film-coating strategy to accurately measure
      small velocity with relatively short and cheap etalon. Laser pointing to the
      etalon is split into two beams with different incident angles with each beam
      going through the etalon in different path. The beam with the smaller incident
      angle is reflected three times before it leaves the etalon, while the other beam
      with larger incident angle goes through the etalon to and forth only once. The
      delay time of the laser beam with smaller incident angle is almost three times
      longer than that of the beam with larger incident angle. In the example of the
      laser with a smaller incident angle, the velocity per fringe of this
      interferometer can be reduced by approximately three times. The etalon is
      optimized so that four laser beams can be penetrated in the vertical direction at
      the meantime. With an etalon of 200 mm in diameter and 150 mm in length, a four
      point bisensitivity velocity interferometer can achieve the velocity per fringe
      of 100 and 350 m/s fringe. A measurement has been successfully undertaken for the
      steel flyer driven by the explosive where the developed interferometer applies.

PMID- 18052465
TI  - Flexible lock-in detection system based on synchronized computer plug-in boards
      applied in sensitive gas spectroscopy.
AB  - We present a flexible and compact, digital, lock-in detection system and its use
      in high-resolution tunable diode laser spectroscopy. The system involves coherent
      sampling, and is based on the synchronization of two data acquisition cards
      running on a single standard computer. A software-controlled arbitrary waveform
      generator is used for laser modulation, and a four-channel analog/digital board
      records detector signals. Gas spectroscopy is performed in the wavelength
      modulation regime. The coherently detected signal is averaged a selected number
      of times before it is stored or analyzed by software-based, lock-in techniques.
      Multiple harmonics of the modulation signal (1f, 2f, 3f, 4f, etc.) are available
      in each single data set. The sensitivity is of the order of 10(-5), being limited
      by interference fringes in the measurement setup. The capabilities of the system
      are demonstrated by measurements of molecular oxygen in ambient air, as well as
      dispersed gas in scattering materials, such as plants and human tissue.

PMID- 18052466
TI  - Manufacturing a thin wire electrostatic trap for ultracold polar molecules.
AB  - We present a detailed description on how to build a thin wire electrostatic trap
      (TWIST) for ultracold polar molecules. It is the first design of an electrostatic
      trap that can be superimposed directly onto a magneto-optical trap (MOT). We can
      thus continuously produce ultracold polar molecules via photoassociation from a
      two species MOT and instantaneously trap them in the TWIST without the need for
      complex transfer schemes. Despite the spatial overlap of the TWIST and the MOT,
      the two traps can be operated and optimized completely independently due to the
      complementary nature of the utilized trapping mechanisms.

PMID- 18052467
TI  - Operating a triple stack microchannel plate-phosphor assembly for single particle
      counting in the 12-300 K temperature range.
AB  - An assembly consisting of a stack of three microchannel plates (MCPs) and a
      phosphor screen anode has been operated over the temperature range from 300 to 12
      K. We report on measurements at 6.4 kHz (using an alpha source) and with dark
      counts only (15 Hz). Without any particle source, the MCP bias current decreased
      by a factor of 2.1 x 10(3) when the temperature was lowered from 300 to 12 K.
      Using the alpha source, and a photomultiplier tube (PMT) to monitor the phosphor
      screen anode, we first observed an increase in the decay time of the phosphor
      from 12 to 45 mus when the temperature was decreased from 300 to 100 K while the
      decay time then decreased and reached a value of 5 mus at 12 K. The pulse height
      distribution from the PMT was measured between 300 and 12 K and shows a spectrum
      typical for a MCP phosphor setup at 300 K and 12 K but is strongly degraded for
      intermediate temperatures. We conclude that the present MCP-phosphor detector
      assembly is well suited for position-sensitive particle counting operation at
      temperatures down to at least 12 K even for count rates beyond 6 kHz. This result
      is crucial and an important part of ongoing developments of new instrumentation
      for investigations of, e.g., interactions involving complex molecular ions with
      internal quantum state control.

PMID- 18052468
TI  - The development of Thomson scattering system on HL-2A tokamak.
AB  - A new Thomson scattering diagnostic system is successfully developed to measure
      core plasma electron temperature (Te) and density (ne) of HL-2A tokamak (major
      radius R=165 cm, minor radius a=40 cm). In this system, a standard lamp
      monochromator combination is utilized for the calibration of spectral responses.
      By sweeping in the range of 750-1200 nm with a step of 2 nm, the work can be done
      automatically for one-point calibration and then for other. Electronic gain
      calibration and gain monitoring are done by pulsed light emitting diode light. By
      utilizing an intense Nd:YAG laser of pulse energy up to 4 J and employing good
      quality interference filters in the five-channel filter polychromator to surpress
      greatly the stray light, the TS system can be routinely used to make measurements
      with good quality data. After each HL-2A plasma discharge, the measured Te and ne
      data are transferred to HL-2A database for lookup and analyses.

PMID- 18052469
TI  - A simple technique to estimate the fully time-resolved x-ray diameter of a z
      pinch.
AB  - Occultations are routinely used to derive information about astronomical objects.
      Here an occultation scheme is used to derive a fully time-resolved estimate of
      the x-ray emitting diameter of a z pinch. By using different filtrations on the
      sensors, one could for example, distinguish the size of the K-line emitting
      region compared to the higher energy K-continuum emitting volume. Or with
      suitable apertures and detector arrays, the pinch diameter could be axially and
      temporally resolved.

PMID- 18052470
TI  - A new multichannel interferometer system on HL-2A.
AB  - A new multichannel HCN interferometer has been developed on HL-2A tokamak, which
      is characterized by two techniques: (1) the wave-guide HCN laser with cavity
      length of 6 m to increase the optical resource power and (2) high response room
      temperature waveguide Schottky diode detectors to obtain good beat signal. The
      space resolution is 7 cm by the use of focusing metal mirrors mounted on the
      vacuum chamber and a compensated optical system. In the 2006 experiment campaign,
      this new interferometer has been applied for plasma density profile and density
      sawtooth measurement.

PMID- 18052471
TI  - High accuracy plasma density measurement using hybrid Langmuir probe and
      microwave interferometer method.
AB  - High spatial resolution plasma density measurements have been taken as part of an
      investigation into magnetic nozzle physics at the NASA/MSFC Propulsion Research
      Center. These measurements utilized a Langmuir triple probe scanned across the
      measurement chord of either of two stationary rf interferometers. By normalizing
      the scanned profile to the microwave interferometer line-integrated density
      measurement for each electrostatic probe measurement, the effect of shot-to-shot
      variation of the line-integrated density can be removed. In addition, by summing
      the voltage readings at each radial position in a transverse scan, the line
      density can be reconstituted, allowing the absolute density to be determined,
      assuming that the shape of the profile is constant from shot to shot. The spatial
      and temporal resolutions of this measurement technique depend on the resolutions
      of the scanned electrostatic probe and the interferometer. The measurement
      accuracy is 9%-15%, which is on the order of the accuracy of the rf
      interferometer. The measurement technique was compared directly with both
      scanning rf interferometer and standard Langmuir probe theory. The hybrid
      technique compares favorably with the scanning rf interferometer, and appears
      more accurate than probe theory alone. Additionally, our measurement technique is
      generally applicable even for nonaxisymmetric plasmas.

PMID- 18052472
TI  - Computer simulation of three-dimensional heavy ion beam trajectory imaging
      techniques used for magnetic field estimation.
AB  - A magnetic field mapping technique via heavy ion beam trajectory imaging is being
      developed on the Madison Symmetric Torus reversed field pinch. This paper
      describes the computational tools created to model camera images of the light
      emitted from a simulated ion beam, reconstruct a three-dimensional trajectory,
      and estimate the accuracy of the reconstruction. First, a computer model is used
      to create images of the torus interior from any candidate camera location. It is
      used to explore the visual field of the camera and thus to guide camera
      parameters and placement. Second, it is shown that a three-dimensional ion beam
      trajectory can be recovered from a pair of perspectively projected trajectory
      images. The reconstruction considers effects due to finite beam size, nonuniform
      beam current density, and image background noise. Third, it is demonstrated that
      the trajectory reconstructed from camera images can help compute magnetic field
      profiles, and might be used as an additional constraint to an equilibrium
      reconstruction code, such as MSTFit.

PMID- 18052473
TI  - Raman calibration of the HT-7 yttrium aluminum garnet Thomson scattering for
      electron density measurements.
AB  - A multipulse neodym doped yttrium aluminum garnet laser Thomson scattering system
      calibrated by the anti-Stokes rotational Raman scattering from nitrogen gas had
      been developed in the HT-7 superconducting Tokmak. By virtue of this system,
      measured electron density results of the plasma were obtained. The results showed
      good repeatability and its total uncertainty was estimated to be +/-18%.

PMID- 18052474
TI  - Shear force control for a terahertz near field microscope.
AB  - We report on the advancement of apertureless terahertz microscopy by active shear
      force control of the scanning probe. Extreme subwavelength spatial resolution and
      a maximized image contrast are achieved by maintaining a tip-surface distance of
      about 20 nm. The constant distance between scanning tip and surface results in
      terahertz images that mirror the dielectric permittivity of the surface.

PMID- 18052475
TI  - Phototriggering system for an ultrahigh-speed video microscopy.
AB  - A phototrigger system is developed as a part of a video microscope mounting an
      ultrahigh-speed video camera capable of image capturing at frame rates as high as
      1x10(6) framess. The extremely high frame rate is achieved by implementing in
      situ image storage. A distinguished feature of the camera is the on-chip
      overwriting mechanism that allows to keep in storage the latest image sequence of
      103 frames; the old signals are continuously drained out of the storage. The
      trigger system is designed to synchronize recording operations with an occurrence
      of a target event within the limited image capturing duration. The target event
      is detected through a sudden change in the output of a sensor mounted to an
      optical port of the microscope. To reduce noise contribution, a two-sensor
      architecture is implemented. One sensor detects the target event while the one
      produces a reference signal used for noise reduction. Both sensors are connected
      to the same optical port by using a specially designed beam splitting unit. To
      provide high sensitivity, avalanche photodiodes are used as photoelements. System
      evaluation shows that its sensitivity is high and response time is less than 3
      mus. This is sufficiently fast for high-speed video-microscopy observations at
      1x10(6) frames/s when using a video camera with a storage of 103 frames. As an
      example, the system was used in a microscopic observation of a soap film
      collapse.

PMID- 18052476
TI  - Single-step electrochemical method for producing very sharp Au scanning tunneling
      microscopy tips.
AB  - A single-step electrochemical method for making sharp gold scanning tunneling
      microscopy tips is described. 3.0M NaCl in 1% perchloric acid is compared to
      several previously reported etchants. The addition of perchloric acid to sodium
      chloride solutions drastically shortens etching times and is shown by
      transmission electron microscopy to produce very sharp tips with a mean radius of
      curvature of 15 nm.

PMID- 18052477
TI  - Apparatus for real-time acoustic imaging of Rayleigh-Benard convection.
AB  - We have designed and built an apparatus for real-time acoustic imaging of
      convective flow patterns in optically opaque fluids. This apparatus takes
      advantage of recent advances in two-dimensional ultrasound transducer array
      technology; it employs a modified version of a commercially available ultrasound
      camera, similar to those employed in nondestructive testing of solids. Images of
      convection patterns are generated by observing the lateral variation of the
      temperature dependent speed of sound via refraction of acoustic plane waves
      passing vertically through the fluid layer. The apparatus has been validated by
      observing convection rolls in both silicone oil and ferrofluid.

PMID- 18052478
TI  - A low temperature scanning tunneling microscope for electronic and force
      spectroscopy.
AB  - In this article, we describe and test a novel way to extend a low temperature
      scanning tunneling microscope with the capability to measure forces. The tuning
      fork that we use for this is optimized to have a high quality factor and
      frequency resolution. Moreover, as this technique is fully compatible with the
      use of bulk tips, it is possible to combine the force measurements with the use
      of superconductive or magnetic tips, advantageous for electronic spectroscopy. It
      also allows us to calibrate both the amplitude and the spring constant of the
      tuning fork easily, in situ and with high precision.

PMID- 18052479
TI  - High-aspect ratio metal tips attached to atomic force microscopy cantilevers with
      controlled angle, length, and radius for electrostatic force microscopy.
AB  - We demonstrate a method to fabricate a high-aspect ratio metal tip attached to
      microfabricated cantilevers with controlled angle, length, and radius, for use in
      electrostatic force microscopy. A metal wire, after gluing it into a guiding slot
      that is cut into the cantilever, is shaped into a long, thin tip using a focused
      ion beam. The high-aspect ratio results in considerable reduction of the
      capacitive force between tip body and sample when compared to a metal coated
      pyramidal tip.

PMID- 18052480
TI  - Quasi-simultaneous imaging/pulling analysis of single polyprotein molecules by
      atomic force microscopy.
AB  - Most of studies in protein nanomechanics have used the atomic force microscope
      (AFM) in its force-measuring mode on immobilized protein repeats (polyproteins)
      as single-molecule markers. Here, we add imaging capabilities to a standard,
      state-of-the-art AFM "puller" and integrate the most powerful programs of
      analysis available for both AFM modes. This unique instrument allows high
      resolution, quasi-simultaneous imaging/force spectroscopy in aqueous solution. We
      demonstrate its capabilities using polyproteins of a model system (titin I27
      domain). This tool should greatly facilitate the development of a much needed
      universal functionalization system for AFM, one that should allow better sample
      control and an improved efficiency of protein immobilization.

PMID- 18052481
TI  - Analyzer-based x-ray phase-contrast microscopy combining channel-cut and
      asymmetrically cut crystals.
AB  - An analyzer-based x-ray phase-contrast microscopy (ABM) setup combining a
      standard analyzer-based x-ray phase-contrast imaging (ABI) setup [nondispersive 4
      crystal setup (Bonse-Hart setup)] and diffraction by asymmetrically cut crystals
      is presented here. An attenuation-contrast microscopy setup with conventional x
      ray source and asymmetrically cut crystals is first analyzed. Edge-enhanced
      effects attributed to phase jumps or refraction/total external reflection on the
      fiber borders were detected. However, the long exposure times and the possibility
      to achieve high contrast microscopies by using extremely low attenuation-contrast
      samples motivated us to assemble the ABM setup using a synchrotron source. This
      setup was found to be useful for low contrast attenuation samples due to the low
      exposure time, high contrast, and spatial resolution found. Moreover, thanks to
      the combination with the nondispersive ABI setup, the diffraction-enhanced x-ray
      imaging algorithm could be applied.

PMID- 18052482
TI  - Setup for in situ x-ray diffraction study of swift heavy ion irradiated
      materials.
AB  - An in situ x-ray diffraction (XRD) setup is designed and installed in the
      materials science beam line of the Pelletron accelerator at the Inter-University
      Accelerator Centre for in situ studies of phase change in swift heavy ion
      irradiated materials. A high vacuum chamber with suitable windows for incident
      and diffracted X-rays is integrated with the goniometer and the beamline.
      Indigenously made liquid nitrogen (LN2) temperature sample cooling unit is
      installed. The snapshots of growth of particles with fluence of 90 MeV Ni ions
      were recorded using in situ XRD experiment, illustrating the potential of this in
      situ facility. A thin film of C60 was used to test the sample cooling unit. It
      shows that the phase of the C60 film transforms from a cubic lattice (at room
      temperature) to a fcc lattice at around T=255 K.

PMID- 18052484
TI  - High precision metrology based microwave effective linewidth measurement
      technique.
AB  - A precision microwave effective linewidth measurement technique for magnetic
      samples has been developed. The measurement utilizes a high-Q cylindrical cavity
      that contains the sample of interest, a highly stable and programable static
      magnetic field source, a computer controlled network analyzer for cavity center
      frequency omega c and quality factor Qc determinations, and the standard
      metrological substitution ABA method for accurate relative omega c and Qc
      measurements. Sequential long term ABA measurements show that the time and
      temperature drifts and random errors are the dominant sources of error, with
      uncertainties in omega c/2pi and Qc in the range of 50 kHz and 25, respectively.
      The ABA method is applied to eliminate these drifts and minimize the random
      errors. For measurements over 25 ABA cycles, accuracy is improved to 0.14 kHz for
      omega c/2pi and 3 for Qc. The temperature variation over a single ABA cycle is
      generally on the order of 10(-3)-10(-5) degrees C and there is no need for any
      further temperature stabilization or correction measures. The overall uncertainty
      in the 10 GHz effective linewidth determinations for a 3 mm diam, 0.5 mm thick
      polycrystalline yttrium iron garnet (YIG) disk is 0.15 Oe or less, well below the
      intrinsic single crystal YIG linewidth. This represents a factor of 10
      improvement in measurement accuracy over previous work.

PMID- 18052483
TI  - Novel impedance cell for low conductive liquids: determination of bulk and
      interface contributions.
AB  - A plane capacitor cell with variable gap has been designed in order to detect the
      complex permittivity of low conductive liquids (up to 500 microS/cm) and the
      impedance of the sample-electrode interface. The novelty of the cell consists of
      the simultaneous presence of the field uniformity ensured by a guard ring, an
      adjustable gap between 300 microm and 6.75 mm (the electrode axial motion
      avoiding any rotation), and the immersion of the capacitor in the sample
      reservoir. The size of the capacitor electrodes and the gap values have been
      tested via the capacitance detection of the in-air cell at 1 kHz. The sample
      measurements have been performed by scanning the frequency range between 15 Hz
      and 2 MHz at four different capacitor gap values. In the paper a method to
      directly extract the bulk complex permittivity and the interface impedance versus
      frequency is presented. It is based on the assumption that the interface
      contribution is independent of the electrode gap, as confirmed (within the
      measurement accuracy) from measurements on all samples investigated. As samples
      of interest, we have chosen two certified electrolytic conductivity standards,
      KCl aqueous solutions having conductivity traceable to SI units; and two polymer
      latex aqueous dispersions of microspheres. Regarding KCl solutions, the
      conductivity measurements are compatible with the reference values within the
      specified uncertainty; the measured permittivities are consistent with the
      literature. For all samples, we have recovered the expected result that the
      interface impedance mainly affects the low frequency range (f<10 kHz).

PMID- 18052485
TI  - Maps of the stress distributions in drying latex films.
AB  - We report on spatially resolved measurements of the mechanical stress in drying
      polymer films. The technique is based on the deflection of a flexible membrane
      serving as the substrate. Assuming that the lateral tension of the membrane is
      the main source of its resistance to deformation, one can show that the local
      surface stress sigma f (x,y) is proportional to the vertical displacement of the
      membrane u z(x,y). The membrane distortion was determined by optical means.
      Measurements taken on drying latex dispersions revealed a maximum of film stress
      at the rim. The heterogeneous stress distribution often persisted after the film
      had become dry.

PMID- 18052486
TI  - Construction and calibration of a 12 T pulsed magnet integrated with a 4 K closed
      cycle refrigerator.
AB  - A low cost 12 T pulsed magnet system has been integrated with a closed-cycle
      helium refrigerator for performing magnetotransport measurements. Minimal delay
      between pulses and ac current excitation with software lock-in to reduce noise
      enables quick but accurate measurements to be performed at temperatures of 4-300
      K up to 12 T. An additional pulsed magnet operating with a liquid nitrogen
      cryostat extends the range up to 19 T. The instrument has been calibrated against
      a commercial superconducting magnet by comparing quantum Hall effect data in a p
      channel SiGe/Si heterostructure, and common issues arising out of pulsed magnet
      usage have been addressed. The versatility of the system is demonstrated through
      magnetotransport measurements in a variety of samples such as heterostructures,
      narrow gap semiconductors, and those exhibiting giant magnetoresistance.

PMID- 18052487
TI  - Finite element design of double bevel anvils of large volume cubic high pressure
      apparatus.
AB  - A double bevel anvil of the cubic high pressure apparatus (CHPA) was developed,
      adopting tungsten carbide as the anvil material. We have performed finite element
      analyses of conventional single bevel anvil and double bevel anvil. The results
      indicate that the double bevel anvil has two advantages. Firstly, to gain the
      same chamber pressure, the oil pressure of CHPA using double bevel anvil
      decreases about 10.8% than that using single bevel anvil. Secondly, double
      beveling can maintain the pressurized seal stability of the sample chamber, which
      is often sacrificed with improve the pressure of sample chamber. The results of
      finite element analyses are well consistent with the experimental results at CHPA
      (SPD-6x1200 type).

PMID- 18052488
TI  - Preparation of TiO2(110)-(1x1) surface via UHV cleavage: an scanning tunneling
      microscopy study.
AB  - TiO2(110) surface was successfully prepared in situ by UHV cleaving of a
      commercial TiO2 crystal. Scanning tunneling microscopy (STM) imaging revealed
      atomically flat more than 1 mum wide terraces with (110) orientation separated by
      steps running in [001] direction, with very low kink density. Atomically resolved
      STM images show periodicity in the [001] and [110] directions with the unit cell
      parameters measured to approximately 3 and 6.5 A, respectively, which are closed
      to the expected values of bulk terminated (1 x 1) surface.

PMID- 18052489
TI  - Method for rapid determination of ion gauge sensitivity factors.
AB  - In ultrahigh vacuum thin film growth processes using gas phase growth precursors,
      the pressure of the gas at or near the substrate is a critical parameter since it
      is directly related to the collision frequency of the precursor with the
      substrate and ultimately to the growth rate. These pressures are usually measured
      using a nude Bayrd-Alpert-type ion gauges, which are generally calibrated for
      nitrogen. Consequently, it is necessary to know the ion gauge sensitivity factor
      that relates the measured pressure to the actual pressure of the growth
      precursor. The purpose of this article is to describe a simple method to obtain
      such sensitivity factors. This method uses a simple gas manifold comprised of
      equipment commonly found in laboratory settings where ultrahigh vacuum work is
      performed. Results are reported for dimethyl silane, monomethyl silane, methane,
      and hydrogen. The gauge sensitivity factors for the latter two gases are known
      and, therefore, provide a basis for validating the method.

PMID- 18052490
TI  - Combined experimental setup for spin- and angle-resolved direct and inverse
      photoemission.
AB  - We present a combined experimental setup for spin- and angle-resolved direct and
      inverse photoemission in the vacuum ultraviolet energy range for measurements of
      the electronic structure below and above the Fermi level. Both techniques are
      installed in one ultrahigh-vacuum chamber and, as a consequence, allow
      quasisimultaneous measurements on one and the same sample preparation. The
      photoemission experiment consists of a gas discharge lamp and an electron energy
      analyzer equipped with a spin polarization detector based on spin-polarized low
      energy electron diffraction. Our homemade inverse-photoemission spectrometer
      comprises a GaAs photocathode as spin-polarized electron source and Geiger-Muller
      counters for photon detection at a fixed energy of 9.9 eV. The total energy
      resolution of the experiment is better than 50 meV for photoemission and better
      than 200 meV for inverse photoemission. The performance of our combined direct
      and inverse-photoemission experiment with respect to angular and energy
      resolutions is exemplified by the Fermi-level crossing of the Cu(111) L-gap
      surface state. Spin-resolved measurements of Co films on Cu(001) are used to
      characterize the Sherman function of the spin polarization detector as well as
      the spin polarization of our electron source.

PMID- 18052491
TI  - Thermal quenching sample chamber for grazing incidence small angle x-ray
      scattering studies of polymer films.
AB  - The second generation of a sample chamber designed for in situ measurement of
      temperature- and time-dependent polymer film nanostructure using the method of
      grazing incidence small angle x-ray scattering is presented. An increased
      operating temperature limit (from 260 to 400 degrees C) with precise control (+/
      0.1 degrees C) at fixed temperatures as well as a fourfold increase in maximum
      instantaneous cooling rate (up to 73 degrees C/s) relative to the first
      generation chamber [M. N. Groves et al, J. Appl. Crystallogr. 39, 120 (2006)] are
      reported. Thermal quenches from 220 to 90 degrees C are shown to be reproducible
      to within +/-1 degrees C of the final temperature. Experimental tests on spin
      coated films of symmetric diblock styrene-butadiene copolymer demonstrate the
      ability to resolve the kinetics of orientation of lamellar domains parallel to
      the silicon substrate, distinct from the initial formation of randomly oriented
      lamellar domains immediately following the thermal quench.

PMID- 18052492
TI  - High-force magnetic tweezers with force feedback for biological applications.
AB  - Magnetic micromanipulation using magnetic tweezers is a versatile biophysical
      technique and has been used for single-molecule unfolding, rheology measurements,
      and studies of force-regulated processes in living cells. This article describes
      an inexpensive magnetic tweezer setup for the application of precisely controlled
      forces up to 100 nN onto 5 microm magnetic beads. High precision of the force is
      achieved by a parametric force calibration method together with a real-time
      control of the magnetic tweezer position and current. High forces are achieved by
      bead-magnet distances of only a few micrometers. Applying such high forces can be
      used to characterize the local viscoelasticity of soft materials in the nonlinear
      regime, or to study force-regulated processes and mechanochemical signal
      transduction in living cells. The setup can be easily adapted to any inverted
      microscope.

PMID- 18052493
TI  - A new satellite-borne neutral wind instrument for thermospheric diagnostics.
AB  - The bulk motion of the neutral gas at altitudes between about 200 and 600 km is
      an important factor in predicting the onset of plasma instabilities that are
      known to distort and/or disrupt high frequency radio communications. These
      neutral winds have historically been quite difficult to measure, especially from
      a moving spacecraft. A new space science instrument called the ram wind sensor
      has been developed to measure the component of the neutral gas velocity that lies
      along the orbit track of a satellite in low Earth orbit. Laboratory tests of an
      engineering model of the instrument have been carried out using a supersonic
      neutral argon beam, in order to validate the measurement concept. The results
      show that the technique is viable for measurements of neutral flow velocities in
      future satellite missions.

PMID- 18052494
TI  - A new switched-capacitor frequency modulated driver for light emitting diodes.
AB  - A new type of drivers for light emitting diodes (LEDs) is introduced based on the
      switched-capacitor frequency modulation. In contrast to conventional constant dc
      current drivers, the current pulse is provided by this new switched-capacitor LED
      driver. In the present driver, the charging capacitor is charged and discharged
      through a LED and the current flow direction is controlled by a metal oxide
      semiconductor switch. The input current (and thus the LED brightness) is
      proportional to the switch clock frequency at relatively low frequencies and
      becomes saturated at relatively high frequencies. This new driver circuit is
      simple and robust and maintains high efficiency for a wide range of input powers.
      In addition, the dimming control is easily realized by modulating clock
      frequency. Finally, this LED driver consumes no dc current and thus provides
      inherent protection to LED in standby mode.

PMID- 18052495
TI  - A new correlation method for high sensitivity current noise measurements.
AB  - The properties of a differential transconductance amplifier coupled with a four
      channel measurement system are exploited in order to reach a very high
      sensitivity in current noise measurements. In particular, it is demonstrated
      that, in proper conditions, the noise contributions coming from the active and
      passive devices that make up the transresistance amplifier can be virtually
      eliminated. Moreover, the proposed measurement method allows the evaluation of
      the impedance of the device under test from noise measurement data. Actual
      measurement results are also reported that demonstrate the effectiveness of the
      proposed approach.

PMID- 18052496
TI  - Separated two-phase flow regime parameter measurement by a high speed ultrasonic
      pulse-echo system.
AB  - In this work, a high speed ultrasonic multitransducer pulse-echo system using a
      four transducer method was used for the dynamic characterization of gas-liquid
      two-phase separated flow regimes. The ultrasonic system consists of an ultrasonic
      pulse signal generator, multiplexer, 10 MHz (0.64 cm) ultrasonic transducers, and
      a data acquisition system. Four transducers are mounted on a horizontal 2.1 cm
      inner diameter circular pipe. The system uses a pulse-echo method sampled every
      0.5 ms for a 1 s duration. A peak detection algorithm (the C-scan mode) is
      developed to extract the location of the gas-liquid interface after signal
      processing. Using the measured instantaneous location of the gas/liquid
      interface, two-phase flow interfacial parameters in separated flow regimes are
      determined such as liquid level and void fraction for stratified wavy and annular
      flow. The shape of the gas-liquid interface and, hence, the instantaneous and
      cross-sectional averaged void fraction is also determined. The results show that
      the high speed ultrasonic pulse-echo system provides accurate results for the
      determination of the liquid level within +/-1.5%, and the time averaged liquid
      level measurements performed in the present work agree within +/-10% with the
      theoretical models. The results also show that the time averaged void fraction
      measurements for a stratified smooth flow, stratified wavy flow, and annular flow
      qualitatively agree with the theoretical predictions.

PMID- 18052497
TI  - Measuring permeability of porous materials at low frequency range via acoustic
      transmitted waves.
AB  - An acoustical transmission method is proposed for measuring permeability of
      porous materials having rigid frame. Permeability is one of the several
      parameters required by acoustical theory to characterize porous materials such as
      plastic foams and fibrous or granular materials. The proposed method is based on
      a temporal model of the direct and inverse scattering problem for the diffusion
      of transient low frequency waves in a homogeneous isotropic slab of porous
      material having a rigid frame. This time domain model of wave propagation was
      initially introduced by the authors [Z.E.A Fellah and C. Depollier, J. Acoust.
      Soc. Am. 107, 683 (2000)]. The viscous losses of the medium are described by the
      model devised by Johnson et al. [J. Fluid. Mech. 176, 379 (1987)]. Reflection and
      transmission scattering operators for a slab of porous material are derived from
      the responses of the medium to an incident acoustic pulse. The permeability is
      determined from the expressions of these operators. Experimental and numerical
      validation results of this method are presented. This method has the advantage of
      being simple, rapid, and efficient.

PMID- 18052498
TI  - Probing elastic modulus and depth of bottom-supported inclusions in model tissues
      using piezoelectric cantilevers.
AB  - We have experimentally investigated the depth sensitivity limit of a
      piezoelectric cantilever tissue elastic modulus sensor and simultaneously
      determined the elastic modulus and the depth of a tumor directly. Using model
      tissues consisting of bottom-supported modeling clay inclusions of various depths
      in a gelatin matrix, we empirically determined that the depth sensitivity limit
      of a piezoelectric cantilever sensor was twice the linear dimension of the
      indentation area (or the cantilever width). Knowing the depth sensitivity limit
      of the individual cantilever sensor as input and treating a model tissue that has
      the gelatin matrix on top and the modeling clay inclusion at the bottom as two
      springs in series, we showed that the elastic moduli and depths of the hard
      inclusions could be simultaneously determined with the elastic modulus profiles
      measured by two cantilevers with different widths as input.

PMID- 18052499
TI  - An accurate air temperature measurement system based on an envelope pulsed
      ultrasonic time-of-flight technique.
AB  - A new microcomputer based air temperature measurement system is presented. An
      accurate temperature measurement is derived from the measurement of sound
      velocity by using an ultrasonic time-of-flight (TOF) technique. The study
      proposes a novel algorithm that combines both amplitude modulation (AM) and phase
      modulation (PM) to get the TOF measurement. The proposed system uses the AM and
      PM envelope square waveform (APESW) to reduce the error caused by inertia delay.
      The APESW ultrasonic driving waveform causes an envelope zero and phase inversion
      phenomenon in the relative waveform of the receiver. To accurately achieve a TOF
      measurement, the phase inversion phenomenon was used to sufficiently identify the
      measurement pulse in the received waveform. Additionally, a counter clock
      technique was combined to compute the phase shifts of the last incomplete cycle
      for TOF. The presented system can obtain 0.1% TOF resolution for the period
      corresponding to the 40 kHz frequency ultrasonic wave. Consequently, with the
      integration of a humidity compensation algorithm, a highly accurate and high
      resolution temperature measurement can be achieved using the accurate TOF
      measurement. Experimental results indicate that the combined standard uncertainty
      of the temperature measurement is approximately 0.39 degrees C. The main
      advantages of this system are high resolution measurements, narrow bandwidth
      requirements, and ease of implementation.

PMID- 18052500
TI  - Active drift compensation applied to nanorod manipulation with an atomic force
      microscope.
AB  - We have developed a simple algorithm to overcome the problem of thermal drift in
      an atomic force microscope (AFM) operating under ambient conditions. Using our
      method, we demonstrate that the AFM tip remains above a 5-nm-high and 50-nm-long
      CdSe nanorod for more than 90 min despite the thermal drift present (6 nm/min).
      We have applied our drift compensation technique to the AFM manipulation of CdSe
      colloidal nanorods lying horizontally on a highly oriented pyrolytic graphite
      surface. Since we have precise control over the position of the AFM tip relative
      to the nanorod, we can choose to either translate or rotate the rod by changing
      the location of the tip-rod interaction point.

PMID- 18052501
TI  - A synchrotron beamline for delivering high purity vacuum ultraviolet photons.
AB  - We report on the current status and performance of the toroidal grating
      monochromator beamline at the Brazilian Synchrotron Light Laboratory (Laboratorio
      Nacional de Luz Sincrotron). This beamline provides photons in the vacuum
      ultraviolet and soft x-ray regions from 12 to 330 eV with three interchangeable
      gratings. We report on the improvement, which allows the possibility of choosing
      the light polarization degree from linear to almost circular. Here, we also
      describe the development of a new apparatus, namely, the mirror-inserted harmonic
      attenuator and calibrating-device with a long length (MIRHACLLE). All beamlines
      based on diffraction gratings suffer from the problem of high harmonics
      contaminations to some extent. The MIRHACLLE provides a way to efficiently
      suppress high harmonics from 25% to 1 ppm in a grazing incidence bending magnet
      beamline. Its principle of operation relays on the absorption of the high energy
      photons in a gas phase region. It allows negligible high harmonics contamination
      for photon energies ranging from 12 eV to the gas first ionization threshold,
      21.6 eV, in the case of neon. We also demonstrate the possibility to use this
      device for energy calibration and resolution evaluation together with any
      experiment needing its filtering capabilities. The device is also very cost
      effective compared to other filters presented previously in the literature.

PMID- 18052502
TI  - A broadband laser plasma x-ray source for application in ultrafast chemical
      structure dynamics.
AB  - A plasma source free from characteristic emission lines is described, based on
      laser irradiation of a water jet in a helium atmosphere. Various key aspects of
      the laser interaction are presented along with practical characterization of the
      observed isotropic approximately 4-10 keV x-ray emissions, measurements of which
      indicate subpicosecond duration. Observations are consistent with a vacuum
      heating plasma mechanism at the helium-water interface and indicate strong
      potential for in-house ultrafast chemical structure dynamics application when
      coupled to contemporary detector developments.

PMID- 18052503
TI  - Dielectric flashover with triple point shielding in a coaxial geometry.
AB  - Increasing performance of vacuum insulator barriers is a common goal in pulsed
      power. Insulating performance is continually being improved while new methods are
      developed. Triple point shielding techniques have been shown to increase
      flashover voltage, but the role of cathode versus anode shielding is still not
      fully understood. Open circuit flashover characteristics were obtained for a
      coaxial geometry to view the effects of triple point shielding for this geometry.
      The tests included applying various combinations of triple point shields on zero
      and +45 degrees insulators. Shielding was tested at the cathode triple point
      outside of the dielectric and at the anode triple point inside the dielectric.
      The role of anode versus cathode triple point shielding was examined. Flashover
      voltage was observed to increase when either a cathode or anode triple point
      shield was applied; however, adding a shield to both regions lowered the
      flashover threshold. Both triple point regions were found to be important and
      dependent on each other for some coaxial geometries.

PMID- 18052504
TI  - Characterization and analysis of a pulse power system based on Marx generator and
      Blumlein.
AB  - A pulse power system (1 MV, 50 kA, and 100 ns) based on Marx generator and
      Blumlein pulse forming line has been studied for characterization of a general
      system. Total erected Marx inductance and series resistance are calculated from
      modular testing of Marx generator and testing of Marx generator with Blumlein.
      The complete pulse power system has been tested with the termination of a liquid
      resistor load for finding the Blumlein characteristic impedance. Equivalent
      electrical circuits during the charging and discharging of the Blumlein are
      constructed from the characterized parameters of the system. These equivalent
      circuits can be used in the analysis of prepulse voltage and droop in the flat
      top of the main pulse in the pulse power systems based on Marx generator and
      Blumlein.

PMID- 18052505
TI  - Development of a two-dimensional dual pendulum thrust stand for Hall thrusters.
AB  - A two-dimensional dual pendulum thrust stand was developed to measure thrust
      vectors [axial and horizontal (transverse) direction thrusts] of a Hall thruster.
      A thruster with a steering mechanism is mounted on the inner pendulum, and thrust
      is measured from the displacement between inner and outer pendulums, by which a
      thermal drift effect is canceled out. Two crossover knife-edges support each
      pendulum arm: one is set on the other at a right angle. They enable the pendulums
      to swing in two directions. Thrust calibration using a pulley and weight system
      showed that the measurement errors were less than 0.25 mN (1.4%) in the main
      thrust direction and 0.09 mN (1.4%) in its transverse direction. The thrust angle
      of the thrust vector was measured with the stand using the thruster.
      Consequently, a vector deviation from the main thrust direction of +/-2.3 degrees
      was measured with the error of +/-0.2 degrees under the typical operating
      conditions for the thruster.

PMID- 18052506
TI  - Lead-free acoustic emission sensors.
AB  - Acoustic emission (AE) sensors have been fabricated using both soft- and hard
      type lead-free (Na0.5K0.5)NbO3-based ceramics. The acoustic and electromechanical
      properties of the ceramics have been determined using the resonance technique.
      The lead-free AE sensors were calibrated using a laser source and compared to a
      commercial sensor. A lead zirconate titanate (PZT) 5H ceramics AE sensor has also
      been fabricated and calibrated for comparison. It was found that the sensitivity
      of lead-free AE sensors is comparable to that of the lead-based PZT sensor. To
      evaluate the sensors for potential application, they have been used in the
      detection of AE in an impact test. The lead-free sensors can reproduce AE signals
      accurately without giving artifacts and have potential use in commercial AE
      systems.

PMID- 18052507
TI  - Surface modes of a sessile water drop: an optical tweezer based study.
AB  - A high-precision method to study the dynamics of two-fluid interfaces using an
      optical tweezer and a phase-sensitive detection technique are described. The
      disturbances set up at the interface are studied by analyzing the motion of an
      optically trapped particle in the bulk of the fluid, i.e., away from the
      interface. The usefulness of the technique is demonstrated for the well-known
      problem of a horizontally vibrated sessile liquid drop. The vibrational modes of
      the liquid drop excited by sinusoidally vibrating the support in a horizontal
      plane appear as resonances in the motion of the trapped particle. The nature of
      the resonance is studied in detail by measuring the real part, the imaginary
      part, and the phase response of the motion of the particle as a function of the
      "effective" size of the liquid drop. Excellent quantitative agreement with the
      theoretically predicted values of the eigenfrequencies and damping of the surface
      modes is obtained.

PMID- 18052508
TI  - Laser-Doppler vibrating tube densimeter for measurements at high temperatures and
      pressures.
AB  - A laser-Doppler vibrometer was used to measure the vibration of a vibrating tube
      densimeter for measuring P-V-T data at high temperatures and pressures. The
      apparatus developed allowed the control of the residence time of the sample so
      that decomposition at high temperatures could be minimized. A function generator
      and piezoelectric crystal was used to excite the U-shaped tube in one of its
      normal modes of vibration. Densities of methanol-water mixtures are reported for
      at 673 K and 40 MPa with an uncertainty of 0.009 g/cm3.

PMID- 18052509
TI  - Combining multiple optical trapping with microflow manipulation for the rapid
      bioanalytics on microparticles in a chip.
AB  - An array of four independent laser traps is combined with a polydimethylsiloxane
      microfluidic chip to form a very compact system allowing parallel processing of
      biological objects. Strong three dimensional trapping allows holding objects such
      as functionalized beads in flows at speeds near 1 mm/s, enabling rapid
      processing. By pressure control of the inlet flows, the trapped objects can be
      put in contact with different solutions for analysis purpose. This setup,
      including a fluorescence excitation-detection scheme, offers the potential to
      perform complex biochemical manipulations on an ensemble of microparticles.

PMID- 18052510
TI  - Atomic force microscopy: loading position dependence of cantilever spring
      constants and detector sensitivity.
AB  - A simple and accurate experimental method is described for determining the
      effective cantilever spring constant and the detector sensitivity of atomic force
      microscopy cantilevers on which a colloidal particle is attached. By attaching
      large (approximately 85 microm diameter) latex particles at various positions
      along the V-shaped cantilevers, we demonstrate how the normal and lateral spring
      constants as well as the sensitivity vary with loading position. Comparison with
      an explicit point-load theoretical model has also been used to verify the
      accuracy of the method.

PMID- 18052511
TI  - Operation of a frequency-narrowed high-beam quality broad-area laser by a
      passively stabilized external cavity technique.
AB  - The average spectral bandwidth of a 2 W broad-area diode laser was narrowed to 5
      GHz with wavelength tunability of up to 12 nm at a center wavelength of 790 nm
      with the use of a Littman-Metcalf external cavity in a displaced configuration.
      The use of lens and combined lens-laser transformation systems allowed precise
      alignment of the beam shaping optics, which led to significant improvements of
      the beam quality and an enhanced suppression of the free-running laser modes. We
      characterize the spatial beam quality of our external cavity diode laser by
      measuring the M2 quality factor and relate this to our measured bandwidths. Our
      external cavity can be configured over a range of cavity lengths and is modular
      in design, enabling access to a broad frequency spectrum for a wide range of
      applications that require high-power, narrow bandwidth operation.

PMID- 18052512
TI  - Simplified small-scale backlight unit tester.
AB  - A novel design is the concept of using charge coupled device camera embedded with
      calibrated image processing algorithm as a two-dimensional luminance meter to
      measure the luminance and uniformity of small-scale backlight of unit. A small
      scale backlight unit tester was successfully realized and performed to verify
      this concept.

PMID- 18052513
TI  - Xenon ion laser-induced fluorescence using a visible tunable diode laser near 680
      nm.
AB  - Laser-induced fluorescence (LIF) measurements have been performed for the first
      time in a low temperature (Te approximately 0.6 eV) Xe plasma using a tunable
      diode laser in the visible range of wavelengths. The transition in Xe II involved
      the (3P1)5d[3]7/2 metastable state and the excitation wavelength was found to be
      680.570+/-0.001 nm (air). LIF measurements of I 2 in a room temperature iodine
      gas cell were used to monitor the wavelength of the laser during the
      measurements.

PMID- 18052514
TI  - The aging school nurse workforce.

PMID- 18052515
TI  - What school nurses need to know about cervical cancer, HPV, and the new vaccine.
AB  - At least 12,000 women are diagnosed with cervical cancer each year in the United
      States, accounting for at least 4,000 deaths. Worldwide, cervical cancer is the
      second most common type of cancer among women. The human papilloma virus (HPV)
      has been linked to at least 70% of all cervical cancer. HPV can be divided into 2
      categories: (a) low risk, which is responsible for genital warts, and (b) high
      risk, which is responsible for cervical cancer. An effective new vaccine has been
      approved that will decrease the spread of infection caused by HPV, therefore
      decreasing the future incidence of cervical cancer and genital warts.
      Understanding the risks of acquiring HPV and the increased risk for cervical
      cancer may lead to enhanced vaccine acceptance.

PMID- 18052516
TI  - School nurses' perceptions of family-centered services: commitment and
      challenges.
AB  - Family-centered service is a service delivery model that recognizes the central
      role of families, builds on their strengths, and seeks to fully involve them in
      all aspects of their child's health, learning, and development. Family-centered
      service has been associated with positive outcomes in health and education and
      has been viewed as best practice. This study examined school nurses' perceptions
      of their work practices with families and the implementation of family-centered
      services in the school health setting. An established instrument, the Measure of
      Processes of Care for Service Providers, was used to survey a convenience sample
      of school nurses practicing in California. Quantitative and qualitative results
      indicated that school nurses value family-centered service and use the core
      elements regularly in their work with families. Qualitative data further
      illustrated school nurses' solid commitment to families even in the face of
      challenges such as high student-nurse ratios, lack of time, and limited support.
      Suggestions for overcoming these barriers include development of parent centers,
      employment of school social workers/case managers, and advocating for changes in
      legislation to support the hiring of more school nurses.

PMID- 18052517
TI  - Empowerment in school nursing practice: a grounded theory approach.
AB  - Professional empowerment is vital to nurses' productivity and job satisfaction. A
      grounded theory study was conducted to describe the basic social process
      experienced by school nurses in relation to professional empowerment. Interviews
      with 10 school nurses led to the development of a situation-specific theory of
      school nurse empowerment, Making a Difference: The Role of the School Nurse in
      the Health of Children in Schools. This theory was derived from four theoretical
      constructs: (a) enlisting support, (b) getting through the day, (c) maintaining
      control over practice, and (d) adjusting to challenges. Interviews revealed that
      knowing at the end of each school day that they made a difference in the health
      of children resulted in feelings of empowerment. Participants cited various areas
      in which their sense of empowerment was limited, including salaries and workload.
      Despite these issues, they believed they had a positive impact on the health of
      children, leading to job satisfaction and feelings of value.

PMID- 18052518
TI  - Evaluating the effectiveness of the Kids Living Fit program: a comparative study.
AB  - After-school programs can be implemented by school nurses to facilitate healthy
      lifestyle choices in children with the goal of decreasing obesity. Kids Living
      Fit (KLF), an after-school program designed by community hospital nurses, was
      implemented in elementary schools and focused on best lifestyle choices regarding
      foods consumed and activities chosen for children in grades 2 through 5. Study
      measures included comparison of body mass index (BMI) percentiles for age and
      gender and waist circumference between two self-selected groups composing a total
      sample size of 185 participants: the KLF intervention group (n = 80) and the no
      intervention/ contrast group (n = 105). The 12-week intervention included a
      weekly fitness program and monthly dietitian presentations. Participants
      completed food and activity diaries and wore pedometers. In pairwise comparisons,
      the KLF group had a significant decrease in BMI percentile between baseline and
      follow-up (-2.3%) compared with the contrast group. The KLF group also
      demonstrated a smaller increase in waist circumference than the contrast group.

PMID- 18052519
TI  - Effectiveness of nutrition education on fast food choices in adolescents.
AB  - Adolescent obesity has become a major health concern in the United States. An
      increased frequency of fast food restaurant dining is associated with higher
      intake of calories and calories from fat. The purpose of this study was to gain
      insight as to how food choices in a "simulated" fast food environment might be
      influenced by nutrition education in a group of adolescents. Ten adolescents were
      asked to choose food items from a fast food restaurant menu. Their chosen meals'
      nutrition make-up (calories, fat, cholesterol, sodium, carbohydrates, protein,
      and fiber) was calculated. Following a 30-minute nutrition education session,
      participants were asked again to choose a meal from the same fast food menu. The
      nutrition make-up of the meal chosen postintervention was compared with the meal
      chosen before the education session. There was a statistically significant (p <
      .05) difference in calories, fat, carbohydrate, and fiber content of the meals
      chosen postintervention. This short nutrition education intervention resulted in
      healthier fast food choices in this group of adolescents.

PMID- 18052520
TI  - Evaluation of a hand washing program for 2nd-graders.
AB  - The purpose of this project was to determine if a multiple-week learner-centered
      hand washing program could improve hand hygiene behaviors of 2nd-graders in a
      northern Illinois public school system. Volunteers from the Rockford Hand Washing
      Coalition went into 19 different classrooms for 4 consecutive weeks and taught a
      learner-centered program. The program consisted of interactive class discussions
      and activities using GlitterBug training devices and agar plate materials. A one
      factor repeated measure analysis of variance indicated a statistically
      significant 34% decrease in the absenteeism rate for students in the intervention
      group. Chi-square analyses on agar plate data indicated that students had cleaner
      hands after washing. Qualitative data from parents and teachers indicated that a
      majority of the students were engaging in hand-washing behavior. These results
      indicate that integrating a learner-centered interactive program in a multiple
      week structure can lead to improvement in hand hygiene behavior.

PMID- 18052521
TI  - School-based administration of ADHD drugs decline, along with diversion, theft,
      and misuse.
AB  - Since 2000 researchers have reported a decline in the administration of attention
      deficit/hyperactivity disorder (ADHD) medications given by school nurses,
      although no decline has been noted in the incidence of ADHD in school-age
      populations. Government data for the same period show reduced levels of
      methylphenidate abuse as measured by its involvement in hospital emergency
      department (ED) admissions. Offsetting this, however, is an increase in the
      involvement of amphetamine-dextroamphetamine in hospital ED admissions for the
      same period. Because ADHD medications are often administered in the school
      setting, a survey of school nurses was undertaken to identify factors related to
      the administration as well as to the diversion, theft, and misuse of ADHD
      medications. Of 311 school nurses responding, 295 (95%) reported a significant or
      moderate decline between 2002 and 2004 in the need for school-based
      administration of ADHD medications. Respondents also reported reductions in
      diversion, theft, and misuse of ADHD drugs.

PMID- 18052522
TI  - A follow-up study of former student health advocates.
AB  - Student health advocates (SHAs) are high school students who, under the
      supervision of the school nurse, provide health education and health promotion
      activities to other students via a peer education model. This 3-year follow-up
      study explored how the SHA experience influences career choice and attitudes of
      the participants. It also examined what motivates students to become SHAs, the
      benefits and drawbacks of SHA participation, how SHA involvement influenced
      career plans, and how SHAs perceive the role of the school nurse. Study results
      indicate that this innovative health education/promotion experience offered an
      opportunity for SHAs to express their interest in health and enhanced their sense
      of belonging, meaningful involvement, connection to learning, and caring
      relationships in the school setting.

PMID- 18052524
TI  - "Human bites in the classroom: incidence, treatment, and complications".

PMID- 18052527
TI  - Congenital viral infections of the brain: lessons learned from lymphocytic
      choriomeningitis virus in the neonatal rat.
AB  - The fetal brain is highly vulnerable to teratogens, including many infectious
      agents. As a consequence of prenatal infection, many children suffer severe and
      permanent brain injury and dysfunction. Because most animal models of congenital
      brain infection do not strongly mirror human disease, the models are highly
      limited in their abilities to shed light on the pathogenesis of these diseases.
      The animal model for congenital lymphocytic choriomeningitis virus (LCMV)
      infection, however, does not suffer from this limitation. LCMV is a well-known
      human pathogen. When the infection occurs during pregnancy, the virus can infect
      the fetus, and the developing brain is particularly vulnerable. Children with
      congenital LCMV infection often have substantial neurological deficits. The
      neonatal rat inoculated with LCMV is a superb model system of human congenital
      LCMV infection. Virtually all of the neuropathologic changes observed in humans
      congenitally infected with LCMV, including microencephaly, encephalomalacia,
      chorioretinitis, porencephalic cysts, neuronal migration disturbances,
      periventricular infection, and cerebellar hypoplasia, are reproduced in the rat
      model. Within the developing rat brain, LCMV selectively targets mitotically
      active neuronal precursors. Thus, the targets of infection and sites of pathology
      depend on host age at the time of infection. The rat model has further shown that
      the pathogenic changes induced by LCMV infection are both virus-mediated and
      immune-mediated. Furthermore, different brain regions simultaneously infected
      with LCMV can undergo widely different pathologic changes, reflecting different
      brain region-virus-immune system interactions. Because the neonatal rat
      inoculated with LCMV so faithfully reproduces the diverse neuropathology observed
      in the human counterpart, the rat model system is a highly valuable tool for the
      study of congenital LCMV infection and of all prenatal brain infections In
      addition, because LCMV induces delayed-onset neuronal loss after the virus has
      been cleared, the neonatal rat infected with LCMV may be an excellent model
      system to study neurodegenerative or psychiatric diseases whose etiologies are
      hypothesized to be virus-induced, such as autism, schizophrenia, and temporal
      lobe epilepsy.

PMID- 18052529
TI  - Avoidance of protein fold disruption in natural virus recombinants.
AB  - With the development of reliable recombination detection tools and an increasing
      number of available genome sequences, many studies have reported evidence of
      recombination in a wide range of virus genera. Recombination is apparently a
      major mechanism in virus evolution, allowing viruses to evolve more quickly by
      providing immediate direct access to many more areas of a sequence space than are
      accessible by mutation alone. Recombination has been widely described amongst the
      insect-transmitted plant viruses in the genus Begomovirus (family Geminiviridae),
      with potential recombination hot- and cold-spots also having been identified.
      Nevertheless, because very little is understood about either the biochemical
      predispositions of different genomic regions to recombine or what makes some
      recombinants more viable than others, the sources of the evolutionary and
      biochemical forces shaping distinctive recombination patterns observed in nature
      remain obscure. Here we present a detailed analysis of unique recombination
      events detectable in the DNA-A and DNA-A-like genome components of bipartite and
      monopartite begomoviruses. We demonstrate both that recombination breakpoint hot-
      and cold-spots are conserved between the two groups of viruses, and that patterns
      of sequence exchange amongst the genomes are obviously non-random. Using a
      computational technique designed to predict structural perturbations in chimaeric
      proteins, we demonstrate that observed recombination events tend to be less
      disruptive than sets of simulated ones. Purifying selection acting against
      natural recombinants expressing improperly folded chimaeric proteins is therefore
      a major determinant of natural recombination patterns in begomoviruses.

PMID- 18052528
TI  - HIV-1 group M conserved elements vaccine.

PMID- 18052530
TI  - Processing of nuclear viroids in vivo: an interplay between RNA conformations.
AB  - Replication of viroids, small non-protein-coding plant pathogenic RNAs, entails
      reiterative transcription of their incoming single-stranded circular genomes, to
      which the (+) polarity is arbitrarily assigned, cleavage of the oligomeric
      strands of one or both polarities to unit-length, and ligation to circular RNAs.
      While cleavage in chloroplastic viroids (family Avsunviroidae) is mediated by
      hammerhead ribozymes, where and how cleavage of oligomeric (+) RNAs of nuclear
      viroids (family Pospiviroidae) occurs in vivo remains controversial. Previous in
      vitro data indicated that a hairpin capped by a GAAA tetraloop is the RNA motif
      directing cleavage and a loop E motif ligation. Here we have re-examined this
      question in vivo, taking advantage of earlier findings showing that dimeric
      viroid (+) RNAs of the family Pospiviroidae transgenically expressed in
      Arabidopsis thaliana are processed correctly. Using this methodology, we have
      mapped the processing site of three members of this family at equivalent
      positions of the hairpin I/double-stranded structure that the upper strand and
      flanking nucleotides of the central conserved region (CCR) can form. More
      specifically, from the effects of 16 mutations on Citrus exocortis viroid
      expressed transgenically in A. thaliana, we conclude that the substrate for in
      vivo cleavage is the conserved double-stranded structure, with hairpin I
      potentially facilitating the adoption of this structure, whereas ligation is
      determined by loop E and flanking nucleotides of the two CCR strands. These
      results have deep implications on the underlying mechanism of both processing
      reactions, which are most likely catalyzed by enzymes different from those
      generally assumed: cleavage by a member of the RNase III family, and ligation by
      an RNA ligase distinct from the only one characterized so far in plants, thus
      predicting the existence of at least a second plant RNA ligase.

PMID- 18052531
TI  - Secreted NS1 of dengue virus attaches to the surface of cells via interactions
      with heparan sulfate and chondroitin sulfate E.
AB  - Dengue virus (DENV) nonstructural protein-1 (NS1) is a secreted glycoprotein that
      is absent from viral particles but accumulates in the supernatant and on the
      plasma membrane of cells during infection. Immune recognition of cell surface NS1
      on endothelial cells has been hypothesized as a mechanism for the vascular
      leakage that occurs during severe DENV infection. However, it has remained
      unclear how NS1 becomes associated with the plasma membrane, as it contains no
      membrane-spanning sequence motif. Using flow cytometric and ELISA-based binding
      assays and mutant cell lines lacking selective glycosaminoglycans, we show that
      soluble NS1 binds back to the surface of uninfected cells primarily via
      interactions with heparan sulfate and chondroitin sulfate E. DENV NS1 binds
      directly to the surface of many types of epithelial and mesenchymal cells yet
      attaches poorly to most peripheral blood cells. Moreover, DENV NS1 preferentially
      binds to cultured human microvascular compared to aortic or umbilical cord vein
      endothelial cells. This binding specificity was confirmed in situ as DENV NS1
      bound to lung and liver but not intestine or brain endothelium of mouse tissues.
      Differential binding of soluble NS1 by tissue endothelium and subsequent
      recognition by anti-NS1 antibodies could contribute to the selective vascular
      leakage syndrome that occurs during severe secondary DENV infection.

PMID- 18052533
TI  - A primer on python for life science researchers.

PMID- 18052532
TI  - Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins
      proteolytically released by Trypanosoma cruzi, are critical for the development
      of protective type-1 responses.
AB  - Although the concept that dendritic cells (DCs) recognize pathogens through the
      engagement of Toll-like receptors is widely accepted, we recently suggested that
      immature DCs might sense kinin-releasing strains of Trypanosoma cruzi through the
      triggering of G-protein-coupled bradykinin B2 receptors (B2R). Here we report
      that C57BL/6.B2R-/- mice infected intraperitoneally with T. cruzi display higher
      parasitemia and mortality rates as compared to B2R+/+ mice. qRT-PCR revealed a 5
      fold increase in T. cruzi DNA (14 d post-infection [p.i.]) in B2R-/- heart, while
      spleen parasitism was negligible in both mice strains. Analysis of recall
      responses (14 d p.i.) showed high and comparable frequencies of IFN-gamma
      producing CD4+ and CD8+ T cells in the spleen of B2R-/- and wild-type mice.
      However, production of IFN-gamma by effector T cells isolated from B2R-/- heart
      was significantly reduced as compared with wild-type mice. As the infection
      continued, wild-type mice presented IFN-gamma-producing (CD4+CD44+ and CD8+CD44+)
      T cells both in the spleen and heart while B2R-/- mice showed negligible
      frequencies of such activated T cells. Furthermore, the collapse of type-1 immune
      responses in B2R-/- mice was linked to upregulated secretion of IL-17 and TNF
      alpha by antigen-responsive CD4+ T cells. In vitro analysis of tissue culture
      trypomastigote interaction with splenic CD11c+ DCs indicated that DC maturation
      (IL-12, CD40, and CD86) is controlled by the kinin/B2R pathway. Further, systemic
      injection of trypomastigotes induced IL-12 production by CD11c+ DCs isolated from
      B2R+/+ spleen, but not by DCs from B2R-/- mice. Notably, adoptive transfer of
      B2R+/+ CD11c+ DCs (intravenously) into B2R-/- mice rendered them resistant to
      acute challenge, rescued development of type-1 immunity, and repressed TH17
      responses. Collectively, our results demonstrate that activation of B2R, a DC
      sensor of endogenous maturation signals, is critically required for development
      of acquired resistance to T. cruzi infection.

PMID- 18052534
TI  - In silico elucidation of the molecular mechanism defining the adverse effect of
      selective estrogen receptor modulators.
AB  - Early identification of adverse effect of preclinical and commercial drugs is
      crucial in developing highly efficient therapeutics, since unexpected adverse
      drug effects account for one-third of all drug failures in drug development. To
      correlate protein-drug interactions at the molecule level with their clinical
      outcomes at the organism level, we have developed an integrated approach to
      studying protein-ligand interactions on a structural proteome-wide scale by
      combining protein functional site similarity search, small molecule screening,
      and protein-ligand binding affinity profile analysis. By applying this
      methodology, we have elucidated a possible molecular mechanism for the previously
      observed, but molecularly uncharacterized, side effect of selective estrogen
      receptor modulators (SERMs). The side effect involves the inhibition of the
      Sacroplasmic Reticulum Ca2+ ion channel ATPase protein (SERCA) transmembrane
      domain. The prediction provides molecular insight into reducing the adverse
      effect of SERMs and is supported by clinical and in vitro observations. The
      strategy used in this case study is being applied to discover off-targets for
      other commercially available pharmaceuticals. The process can be included in a
      drug discovery pipeline in an effort to optimize drug leads and reduce unwanted
      side effects.

PMID- 18052536
TI  - Computational biology in Cuba: an opportunity to promote science in a developing
      country.

PMID- 18052537
TI  - Ten simple rules for graduate students.

PMID- 18052535
TI  - STDP in a bistable synapse model based on CaMKII and associated signaling
      pathways.
AB  - The calcium/calmodulin-dependent protein kinase II (CaMKII) plays a key role in
      the induction of long-term postsynaptic modifications following calcium entry.
      Experiments suggest that these long-term synaptic changes are all-or-none switch
      like events between discrete states. The biochemical network involving CaMKII and
      its regulating protein signaling cascade has been hypothesized to durably
      maintain the evoked synaptic state in the form of a bistable switch. However, it
      is still unclear whether experimental LTP/LTD protocols lead to corresponding
      transitions between the two states in realistic models of such a network. We
      present a detailed biochemical model of the CaMKII autophosphorylation and the
      protein signaling cascade governing the CaMKII dephosphorylation. As previously
      shown, two stable states of the CaMKII phosphorylation level exist at resting
      intracellular calcium concentration, and high calcium transients can switch the
      system from the weakly phosphorylated (DOWN) to the highly phosphorylated (UP)
      state of the CaMKII (similar to a LTP event). We show here that increased CaMKII
      dephosphorylation activity at intermediate Ca(2+) concentrations can lead to
      switching from the UP to the DOWN state (similar to a LTD event). This can be
      achieved if protein phosphatase activity promoting CaMKII dephosphorylation
      activates at lower Ca(2+) levels than kinase activity. Finally, it is shown that
      the CaMKII system can qualitatively reproduce results of plasticity outcomes in
      response to spike-timing dependent plasticity (STDP) and presynaptic stimulation
      protocols. This shows that the CaMKII protein network can account for both
      induction, through LTP/LTD-like transitions, and storage, due to its bistability,
      of synaptic changes.

PMID- 18052538
TI  - Using likelihood-free inference to compare evolutionary dynamics of the protein
      networks of H. pylori and P. falciparum.
AB  - Gene duplication with subsequent interaction divergence is one of the primary
      driving forces in the evolution of genetic systems. Yet little is known about the
      precise mechanisms and the role of duplication divergence in the evolution of
      protein networks from the prokaryote and eukaryote domains. We developed a novel,
      model-based approach for Bayesian inference on biological network data that
      centres on approximate Bayesian computation, or likelihood-free inference.
      Instead of computing the intractable likelihood of the protein network topology,
      our method summarizes key features of the network and, based on these, uses a
      MCMC algorithm to approximate the posterior distribution of the model parameters.
      This allowed us to reliably fit a flexible mixture model that captures hallmarks
      of evolution by gene duplication and subfunctionalization to protein interaction
      network data of Helicobacter pylori and Plasmodium falciparum. The 80% credible
      intervals for the duplication-divergence component are [0.64, 0.98] for H. pylori
      and [0.87, 0.99] for P. falciparum. The remaining parameter estimates are not
      inconsistent with sequence data. An extensive sensitivity analysis showed that
      incompleteness of PIN data does not largely affect the analysis of models of
      protein network evolution, and that the degree sequence alone barely captures the
      evolutionary footprints of protein networks relative to other statistics. Our
      likelihood-free inference approach enables a fully Bayesian analysis of a complex
      and highly stochastic system that is otherwise intractable at present. Modelling
      the evolutionary history of PIN data, it transpires that only the simultaneous
      analysis of several global aspects of protein networks enables credible and
      consistent inference to be made from available datasets. Our results indicate
      that gene duplication has played a larger part in the network evolution of the
      eukaryote than in the prokaryote, and suggests that single gene duplications with
      immediate divergence alone may explain more than 60% of biological network data
      in both domains.

PMID- 18052539
TI  - CATHEDRAL: a fast and effective algorithm to predict folds and domain boundaries
      from multidomain protein structures.
AB  - We present CATHEDRAL, an iterative protocol for determining the location of
      previously observed protein folds in novel multidomain protein structures.
      CATHEDRAL builds on the features of a fast secondary-structure-based method
      (using graph theory) to locate known folds within a multidomain context and a
      residue-based, double-dynamic programming algorithm, which is used to align
      members of the target fold groups against the query protein structure to identify
      the closest relative and assign domain boundaries. To increase the fidelity of
      the assignments, a support vector machine is used to provide an optimal scoring
      scheme. Once a domain is verified, it is excised, and the search protocol is
      repeated in an iterative fashion until all recognisable domains have been
      identified. We have performed an initial benchmark of CATHEDRAL against other
      publicly available structure comparison methods using a consensus dataset of
      domains derived from the CATH and SCOP domain classifications. CATHEDRAL shows
      superior performance in fold recognition and alignment accuracy when compared
      with many equivalent methods. If a novel multidomain structure contains a known
      fold, CATHEDRAL will locate it in 90% of cases, with <1% false positives. For
      nearly 80% of assigned domains in a manually validated test set, the boundaries
      were correctly delineated within a tolerance of ten residues. For the remaining
      cases, previously classified domains were very remotely related to the query
      chain so that embellishments to the core of the fold caused significant
      differences in domain sizes and manual refinement of the boundaries was
      necessary. To put this performance in context, a well-established sequence method
      based on hidden Markov models was only able to detect 65% of domains, with 33% of
      the subsequent boundaries assigned within ten residues. Since, on average, 50% of
      newly determined protein structures contain more than one domain unit, and
      typically 90% or more of these domains are already classified in CATH, CATHEDRAL
      will considerably facilitate the automation of protein structure classification.

PMID- 18052540
TI  - Small regulatory RNAs may sharpen spatial expression patterns.
AB  - The precise establishment of gene expression patterns is a crucial step in
      development. Formation of a sharp boundary between high and low spatial
      expression domains requires a genetic mechanism that exhibits sensitivity, yet is
      robust to fluctuations, a demand that may not be easily achieved by morphogens
      alone. Recently, it has been demonstrated that small RNAs (and, in particular,
      microRNAs) play many roles in embryonic development. Whereas some RNAs are
      essential for embryogenesis, others are limited to fine-tuning a predetermined
      gene expression pattern. Here, we explore the possibility that small RNAs
      participate in sharpening a gene expression profile that was crudely established
      by a morphogen. To this end, we study a model in which small RNAs interact with a
      target gene and diffusively move from cell to cell. Though diffusion generally
      smoothens spatial expression patterns, we find that intercellular mobility of
      small RNAs is actually critical in sharpening the interface between target
      expression domains in a robust manner. This sharpening occurs as small RNAs
      diffuse into regions of low mRNA expression and eliminate target molecules
      therein, but cannot affect regions of high mRNA levels. We discuss the
      applicability of our results, as examples, to the case of leaf polarity
      establishment in maize and Hox patterning in the early Drosophila embryo. Our
      findings point out the functional significance of some mechanistic properties,
      such as mobility of small RNAs and the irreversibility of their interactions.
      These properties are yet to be established directly for most classes of small
      RNAs. An indirect yet simple experimental test of the proposed mechanism is
      suggested in some detail.

PMID- 18052542
TI  - Predicting protein function with hierarchical phylogenetic profiles: the Gene3D
      Phylo-Tuner method applied to eukaryotic genomes.
AB  - "Phylogenetic profiling" is based on the hypothesis that during evolution
      functionally or physically interacting genes are likely to be inherited or
      eliminated in a codependent manner. Creating presence-absence profiles of
      orthologous genes is now a common and powerful way of identifying functionally
      associated genes. In this approach, correctly determining orthology, as a means
      of identifying functional equivalence between two genes, is a critical and
      nontrivial step and largely explains why previous work in this area has mainly
      focused on using presence-absence profiles in prokaryotic species. Here, we
      demonstrate that eukaryotic genomes have a high proportion of multigene families
      whose phylogenetic profile distributions are poor in presence-absence information
      content. This feature makes them prone to orthology mis-assignment and unsuited
      to standard profile-based prediction methods. Using CATH structural domain
      assignments from the Gene3D database for 13 complete eukaryotic genomes, we have
      developed a novel modification of the phylogenetic profiling method that uses
      genome copy number of each domain superfamily to predict functional
      relationships. In our approach, superfamilies are subclustered at ten levels of
      sequence identity-from 30% to 100%-and phylogenetic profiles built at each level.
      All the profiles are compared using normalised Euclidean distances to identify
      those with correlated changes in their domain copy number. We demonstrate that
      two protein families will "auto-tune" with strong co-evolutionary signals when
      their profiles are compared at the similarity levels that capture their
      functional relationship. Our method finds functional relationships that are not
      detectable by the conventional presence-absence profile comparisons, and it does
      not require a priori any fixed criteria to define orthologous genes.

PMID- 18052541
TI  - Gamma oscillations of spiking neural populations enhance signal discrimination.
AB  - Selective attention is an important filter for complex environments where
      distractions compete with signals. Attention increases both the gamma-band power
      of cortical local field potentials and the spike-field coherence within the
      receptive field of an attended object. However, the mechanisms by which gamma
      band activity enhances, if at all, the encoding of input signals are not well
      understood. We propose that gamma oscillations induce binomial-like spike-count
      statistics across noisy neural populations. Using simplified models of spiking
      neurons, we show how the discrimination of static signals based on the population
      spike-count response is improved with gamma induced binomial statistics. These
      results give an important mechanistic link between the neural correlates of
      attention and the discrimination tasks where attention is known to enhance
      performance. Further, they show how a rhythmicity of spike responses can enhance
      coding schemes that are not temporally sensitive.

PMID- 18052543
TI  - Intragenomic matching reveals a huge potential for miRNA-mediated regulation in
      plants.
AB  - microRNAs (miRNAs) are important post-transcriptional regulators, but the extent
      of this regulation is uncertain, both with regard to the number of miRNA genes
      and their targets. Using an algorithm based on intragenomic matching of potential
      miRNAs and their targets coupled with support vector machine classification of
      miRNA precursors, we explore the potential for regulation by miRNAs in three
      plant genomes: Arabidopsis thaliana, Populus trichocarpa, and Oryza sativa. We
      find that the intragenomic matching in conjunction with a supervised learning
      approach contains enough information to allow reliable computational prediction
      of miRNA candidates without requiring conservation across species. Using this
      method, we identify approximately 1,200, approximately 2,500, and approximately
      2,100 miRNA candidate genes capable of extensive base-pairing to potential target
      mRNAs in A. thaliana, P. trichocarpa, and O. sativa, respectively. This is more
      than five times the number of currently annotated miRNAs in the plants. Many of
      these candidates are derived from repeat regions, yet they seem to contain the
      features necessary for correct processing by the miRNA machinery. Conservation
      analysis indicates that only a few of the candidates are conserved between the
      species. We conclude that there is a large potential for miRNA-mediated
      regulatory interactions encoded in the genomes of the investigated plants. We
      hypothesize that some of these interactions may be realized under special
      environmental conditions, while others can readily be recruited when organisms
      diverge and adapt to new niches.

PMID- 18052544
TI  - Predicting gene expression from sequence: a reexamination.
AB  - Although much of the information regarding genes' expressions is encoded in the
      genome, deciphering such information has been very challenging. We reexamined
      Beer and Tavazoie's (BT) approach to predict mRNA expression patterns of 2,587
      genes in Saccharomyces cerevisiae from the information in their respective
      promoter sequences. Instead of fitting complex Bayesian network models, we
      trained naive Bayes classifiers using only the sequence-motif matching scores
      provided by BT. Our simple models correctly predict expression patterns for 79%
      of the genes, based on the same criterion and the same cross-validation (CV)
      procedure as BT, which compares favorably to the 73% accuracy of BT. The fact
      that our approach did not use position and orientation information of the
      predicted binding sites but achieved a higher prediction accuracy, motivated us
      to investigate a few biological predictions made by BT. We found that some of
      their predictions, especially those related to motif orientations and positions,
      are at best circumstantial. For example, the combinatorial rules suggested by BT
      for the PAC and RRPE motifs are not unique to the cluster of genes from which the
      predictive model was inferred, and there are simpler rules that are statistically
      more significant than BT's ones. We also show that CV procedure used by BT to
      estimate their method's prediction accuracy is inappropriate and may have
      overestimated the prediction accuracy by about 10%.

PMID- 18052552
TI  - Recognition and treatment of panic disorder.
AB  - Panic disorder is a common, disabling condition that affects 3% to 5% of the
      world's population. Although it is treatable, panic disorder goes unrecognized
      and untreated in many patients. Patients with panic disorder have an increased
      risk for other psychiatric disorders, especially other anxiety disorders, and
      panic disorder is associated with other medical conditions such as migraines,
      fibromyalgia, and irritable bowel syndrome. Clinicians treating panic disorder
      must be able to recognize the disorder, differentiate it from other disorders in
      which panic attacks are part of the symptomatology, and map out an individualized
      treatment plan for each patient. This presentation discusses the importance of
      collaboration between doctor and patient and details available treatment options,
      including antidepressants, benzodiazepines, and cognitive-behavioral therapy.

PMID- 18052545
TI  - Direct inference of SNP heterozygosity rates and resolution of LOH detection.
AB  - Single nucleotide polymorphisms (SNPs) have been increasingly utilized to
      investigate somatic genetic abnormalities in premalignancy and cancer. LOH is a
      common alteration observed during cancer development, and SNP assays have been
      used to identify LOH at specific chromosomal regions. The design of such studies
      requires consideration of the resolution for detecting LOH throughout the genome
      and identification of the number and location of SNPs required to detect genetic
      alterations in specific genomic regions. Our study evaluated SNP distribution
      patterns and used probability models, Monte Carlo simulation, and real human
      subject genotype data to investigate the relationships between the number of
      SNPs, SNP HET rates, and the sensitivity (resolution) for detecting LOH. We
      report that variances of SNP heterozygosity rate in dbSNP are high for a large
      proportion of SNPs. Two statistical methods proposed for directly inferring SNP
      heterozygosity rates require much smaller sample sizes (intermediate sizes) and
      are feasible for practical use in SNP selection or verification. Using HapMap
      data, we showed that a region of LOH greater than 200 kb can be reliably
      detected, with losses smaller than 50 kb having a substantially lower detection
      probability when using all SNPs currently in the HapMap database. Higher
      densities of SNPs may exist in certain local chromosomal regions that provide
      some opportunities for reliably detecting LOH of segment sizes smaller than 50
      kb. These results suggest that the interpretation of the results from genome-wide
      scans for LOH using commercial arrays need to consider the relationships among
      inter-SNP distance, detection probability, and sample size for a specific study.
      New experimental designs for LOH studies would also benefit from considering the
      power of detection and sample sizes required to accomplish the proposed aims.

PMID- 18052546
TI  - Retinal wave behavior through activity-dependent refractory periods.
AB  - In the developing mammalian visual system, spontaneous retinal ganglion cell
      (RGC) activity contributes to and drives several aspects of visual system
      organization. This spontaneous activity takes the form of spreading patches of
      synchronized bursting that slowly advance across portions of the retina. These
      patches are non-repeating and tile the retina in minutes. Several transmitter
      systems are known to be involved, but the basic mechanism underlying wave
      production is still not well-understood. We present a model for retinal waves
      that focuses on acetylcholine mediated waves but whose principles are adaptable
      to other developmental stages. Its assumptions are that a) spontaneous
      depolarizations of amacrine cells drive wave activity; b) amacrine cells are
      locally connected, and c) cells receiving more input during their depolarization
      are subsequently less responsive and have longer periods between spontaneous
      depolarizations. The resulting model produces waves with non-repeating borders
      and randomly distributed initiation points. The wave generation mechanism appears
      to be chaotic and does not require neural noise to produce this wave behavior.
      Variations in parameter settings allow the model to produce waves that are
      similar in size, frequency, and velocity to those observed in several species.
      Our results suggest that retinal wave behavior results from activity-dependent
      refractory periods and that the average velocity of retinal waves depends on the
      duration a cell is excitatory: longer periods of excitation result in slower
      waves. In contrast to previous studies, we find that a single layer of cells is
      sufficient for wave generation. The principles described here are very general
      and may be adaptable to the description of spontaneous wave activity in other
      areas of the nervous system.

PMID- 18052553
TI  - A clinician's view of the data on bipolar disorder.
AB  - Limited data on patients with bipolar disorder in the maintenance phase makes
      implementing evidence-based treatments for maintenance therapy difficult. But,
      clinicians can practice evidence-based treatment by applying the data to
      individual patient's needs. The clinician provides the knowledge base, which
      should then by aligned with individual patient factors that may have an effect on
      treatment. Implementing this dynamic clinician-patient alliance and
      individualizing treatment gives patients their best possible outcome.

PMID- 18052554
TI  - The effect of stimulant treatment for ADHD on later substance abuse and the
      potential for medication misuse, abuse, and diversion.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is known to be a strong risk
      factor for substance use disorders (SUD) in adolescence and in adulthood.
      Research shows that stimulant treatment does not increase the risk of SUD in
      adolescents or adults with ADHD but rather that stimulant treatments may have a
      protective effect. However, 2 in 10 youths with ADHD misuse their medication.
      Recent evidence suggests that slow uptake of medication in the brain allows for
      effective treatment without patients experiencing the euphoric qualities of
      immediate-release agents that lead to abuse or diversion. As a result, extended
      release products and different formulations, such as lisdexamfetamine dimesylate
      (LDX), are less likely to be misused and diverted and may have lower abuse
      potential.

PMID- 18052556
TI  - Virtual reality exposure therapy for the treatment of posttraumatic stress
      disorder following September 11, 2001.
AB  - OBJECTIVE: This preliminary study endeavored to evaluate the use of virtual
      reality (VR) enhanced exposure therapy for the treatment of posttraumatic stress
      disorder (PTSD) consequent to the World Trade Center attacks of September 11,
      2001. METHOD: Participants were assigned to a VR treatment (N = 13) or a waitlist
      control (N = 8) group and were mostly middle-aged, male disaster workers. All
      participants were diagnosed with PTSD according to DSM-IV-TR criteria using the
      Clinician-Administered PTSD Scale (CAPS). The study was conducted between
      February 2002 and August 2005 in offices located in outpatient buildings of a
      hospital campus. RESULTS: Analysis of variance showed a significant interaction
      of time by group (p < .01) on CAPS scores, with a between-groups posttreatment
      effect size of 1.54. The VR group showed a significant decline in CAPS scores
      compared with the waitlist group (p < .01). CONCLUSIONS: Our preliminary data
      suggest that VR is an effective treatment tool for enhancing exposure therapy for
      both civilians and disaster workers with PTSD and may be especially useful for
      those patients who cannot engage in imaginal exposure therapy.

PMID- 18052557
TI  - Vitamin B6 treatment for tardive dyskinesia: a randomized, double-blind, placebo
      controlled, crossover study.
AB  - BACKGROUND: Tardive dyskinesia (TD) is a significant clinical problem. Vitamin
      B(6) is a potent antioxidant and takes part in almost all of the possible
      mechanisms that are suggested as being associated with appearance of TD. The aims
      of this study were (1) to reexamine the efficacy and safety of higher doses of
      vitamin B(6) versus placebo in a greater sample of patients for a longer time and
      (2) to evaluate the carryover effect of vitamin B(6). METHOD: A 26-week, double
      blind, placebo-controlled trial was conducted in a university-based research
      clinic from August 2002 to January 2005 on 50 inpatients with DSM-IV diagnoses of
      schizophrenia or schizoaffective disorder and TD. In a double-blind crossover
      paradigm, all study subjects were randomly assigned to start treatment with
      either vitamin B(6) (daily dose of 1200 mg) or placebo. After 12 weeks of
      treatment and then a 2-week washout, subjects were crossed over to receive the
      other treatment for 12 weeks. The primary outcome measure was the change from
      baseline in Extra-pyramidal Symptom Rating Scale (ESRS) scores. RESULTS: The mean
      decrease in ESRS clinical global impression scores from baseline to endpoint was
      2.4 points in patients treated with vitamin B(6) and 0.2 points in patients
      treated with placebo (p < .0001). The mean decrease in the parkinsonism subscale
      score was 18.5 points and 1.4 points, respectively (p < .00001), and the mean
      decrease in the dyskinesia subscale score was 5.2 points and -0.8 points,
      respectively (p < .0001). CONCLUSION: Vitamin B(6) appears to be effective in
      reducing symptoms of TD. The specific mechanisms by which vitamin B(6) attenuates
      symptoms of TD are not clear.

PMID- 18052558
TI  - Diagnosing co-occurring substance-related disorders: agreement between SCID,
      Hispanic clinicians, and Non-Hispanic clinicians.
AB  - OBJECTIVE: Given the composition of the mental health and substance abuse
      workforce in the United States, Hispanic immigrants are often assigned to non
      Hispanic, English-speaking clinicians. This produces challenges in communication
      and in understanding linguistic and cultural nuances and greatly impacts the
      accuracy of diagnoses and the delivery of appropriate services. With the
      inclusion of objective criteria in diagnostic categories, clinician-to-clinician
      agreement ought not to be impacted by the ethnicity of the client or the
      clinician. Both practice and research, however, suggest that this is not the
      case, particularly when diagnosing co-occurring mental health and substance abuse
      disorders. We explored the degree to which Hispanic and non-Hispanic clinicians
      agreed with each other and with the Structured Clinical Interview for DSM-IV-TR,
      Research Version (SCID) when diagnosing co-occurring substance-related disorders.
      METHOD: Using a naturalistic design, 88 adult clients were videotaped in
      diagnostic intake interviews (utilizing the DSM-IV-TR) with Hispanic or non
      Hispanic clinicians. Videotapes were then viewed and rated by clinicians who were
      ethnically cross-matched to those on tape. Clients were also administered the
      SCID. Data were collected from September 15, 2003, through February 7, 2005.
      RESULTS: Non-Hispanic clinicians diagnosed significantly more substance-related
      disorders than Hispanic clinicians, and both Hispanic and non-Hispanic clinicians
      significantly under-diagnosed substance-related diagnoses compared to the SCID.
      Clinicians had very low diagnostic reliability with each other and with the SCID.
      Implications for the assessment, diagnosis, and treatment of co-occurring
      substance-related disorders are discussed. CONCLUSION: Findings seem to concur
      with past research suggesting that clinicians may be influenced by factors other
      than the diagnostic criteria (e.g., cultural and social biases) when diagnosing,
      and that they may make erroneous attributions of pathology when diagnosing across
      cultures.

PMID- 18052559
TI  - A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate
      in adult outpatients with major depressive disorder.
AB  - OBJECTIVE: This study evaluated the efficacy and tolerability of desvenlafaxine
      succinate (desvenlafaxine) in the treatment of major depressive disorder (MDD).
      METHOD: In this 8-week, multicenter, randomized, double-blind, placebo-controlled
      trial, adult outpatients (aged 18-75 years) with a primary diagnosis of MDD (DSM
      IV criteria) were randomly assigned to treatment with desvenlafaxine (100-200
      mg/day) or placebo. The primary outcome measure was the 17-item Hamilton Rating
      Scale for Depression (HAM-D(17)) score at final on-therapy evaluation. The
      Clinical Global Impressions-Improvement scale (CGI-I) was the key secondary
      measure. Other secondary measures included the Montgomery-Asberg Depression
      Rating Scale (MADRS), Clinical Global Impressions-Severity of Illness scale,
      Visual Analog Scale-Pain Intensity (VAS-PI) overall and subcomponent scores, and
      HAM-D(17) response and remission rates. The study was conducted from June 2003 to
      May 2004. RESULTS: Of the 247 patients randomly assigned to treatment, 234
      comprised the intent-to-treat population. Following titration, mean daily
      desvenlafaxine doses ranged from 179 to 195 mg/day. At endpoint, there were no
      significant differences in scores between the desvenlafaxine (N = 120) and
      placebo (N = 114) groups on the HAM-D(17) or CGI-I. However, the desvenlafaxine
      group had significantly greater improvement in MADRS scores (p = .047) and in VAS
      PI overall pain (p = .008), back pain (p = .006), and arm, leg, or joint pain (p
      < .001) scores than the placebo group. The most common treatment-emergent adverse
      events (at least 10% and twice the rate of placebo) were nausea, dry mouth,
      constipation, anorexia, somnolence, and nervousness. CONCLUSION: Desvenlafaxine
      was generally safe and well tolerated. In this study, it did not show
      significantly greater efficacy than placebo on the primary or key secondary
      efficacy endpoints, but it did demonstrate efficacy on an alternate depression
      scale and pain measure associated with MDD. CLINICAL TRIALS REGISTRATION:
      ClinicalTrials.gov identifier NCT00063206.

PMID- 18052560
TI  - A comparison of selected risk factors for unipolar depressive disorder, bipolar
      affective disorder, schizoaffective disorder, and schizophrenia from a danish
      population-based cohort.
AB  - OBJECTIVE: Growing evidence of an etiologic overlap between schizophrenia and
      bipolar disorder has become increasingly difficult to disregard. In this study,
      we examined paternal age, urbanicity of place of birth, being born "small for
      gestational age," and parental loss as risk factors for primarily schizophrenia
      and bipolar disorder, but also unipolar depressive disorder and schizo-affective
      disorder. Furthermore, we examined the incidence of the disorders in a population
      based cohort and evaluated our results in the context of the Kraepelinian
      dichotomization. METHOD: We established a register-based cohort study of more
      than 2 million persons born in Denmark between January 1, 1955, and July 1, 1987.
      Overall follow-up began on January 1, 1973 and ended on June 30, 2005. Relative
      risks for schizophrenia, bipolar disorder, unipolar depressive disorder, and
      schizoaffective disorder (ICD-8 or ICD-10) were estimated by survival analysis,
      using Poisson regression. RESULTS: Differences were found in age-specific
      incidences. Loss of a parent (especially by suicide) was a risk factor for all 4
      disorders. High paternal age and urbanization at birth were risk factors for
      schizophrenia. Children born pre-term had an excess risk of all disorders except
      schizophrenia if they were born "small for gestational age." CONCLUSIONS: An
      overlap in the risk factors examined in this study was found, and the differences
      between the phenotypes were quantitative rather than qualitative, which suggests
      a genetic and environmental overlap between the disorders. However, large gender
      differences and differences in the age-specific incidences in the 4 disorders
      were present, favoring the Kraepelinian dichotomization.

PMID- 18052561
TI  - Blood glucose and schizophrenia: a systematic review of prospective randomized
      clinical trials.
AB  - OBJECTIVE: Most of the data evaluating the potential relationship between
      diabetes, schizophrenia, and anti-psychotics currently derive from retrospective
      analysis. Relevant confounders of such data include screening and selection bias.
      Prospective data collected from randomized controlled trials may reduce such
      biases. As no single trial has glucose comparisons as a primary endpoint, we
      undertook a systematic review of available data. DATA SOURCES: Embase,
      HealthStar, MEDLINE, Pre-MEDLINE, and PsycINFO databases were searched online for
      relevant articles. Abstracts from major congresses held between January 2000 and
      April 2006 were included. Search terms included all currently available
      antipsychotics: olanzapine, risperidone, clozapine, quetiapine, ziprasidone,
      aripiprazole, haloperidol, chlorpromazine, and zotepine. STUDY SELECTION:
      Prospective clinical trials involving schizophrenia patients with no stated
      previous glucose abnormalities randomly assigned to cohorts receiving active or
      placebo comparator antipsychotic medications were included with no restrictions
      on study length. 16 studies were from peer-reviewed publications, 4 were from
      posters at major congresses, and 2 were available only on Internet-based sites.
      DATA EXTRACTION: Glucose parameters reported included fasting and random glucose
      and glycosylated hemoglobin. Data reported included mean changes and categorical
      reports of abnormal levels. DATA SYNTHESIS: Data were available in 6329 patients
      from 22 trials. The most common comparator agents were aripiprazole and
      olanzapine in 4 studies including 1432 patients. 14 studies reported fasting and
      9 studies reported nonfasting data. 15 studies were a minimum of 5 months, with 8
      studies of at least 1 year's duration. No consistent significant glucose
      differences were found between any comparator antipsychotics or placebo in any
      trial. CONCLUSIONS: In contrast to some of the retrospective data, an analysis of
      prospective data from randomized clinical trials showed no consistent significant
      differences in the incidence of treatment-emergent glucose abnormalities in
      patients treated with antipsychotics. The reduction in both screening and
      selection biases may be relevant. Although one third of the studies had at least
      1 year's duration, the data are not sufficient to reach conclusions regarding
      patients receiving longer-term treatment with atypical antipsychotics.

PMID- 18052562
TI  - Gabapentin reduces alcohol consumption and craving: a randomized, double-blind,
      placebo-controlled trial.
AB  - OBJECTIVE: This study examined the efficacy of a 28-day gabapentin treatment in
      reducing alcohol consumption and craving. METHOD: A randomized, double-blind,
      placebo-controlled trial was performed in a Brazilian public outpatient drug
      treatment center, with 60 male alcohol-dependent subjects with a mean age of 44
      years and an average of 27 years of alcohol use, who consumed 17 drinks per day
      (165-170 g/day) over the past 90 days before baseline and had no other
      significant medical or psychiatric condition. Subjects were recruited between
      July 8, 2004, and February 24, 2005. Following screening, 60 subjects were
      selected and received diazepam and vitamins as treatment for acute withdrawal for
      at least 7 days. After the detoxification treatment, 30 subjects were randomly
      assigned to receive gabapentin (300 mg twice daily) for 4 weeks, and 30 subjects,
      with similar baseline characteristics, were randomly assigned to receive matching
      placebo tablets for the same period. RESULTS: After 28 days of treatment, the
      gabapentin group showed a significant reduction in both number of drinks per day
      and mean percentage of heavy drinking days (p = .02 for both), and an increase in
      the percentage of days of abstinence (p = .008), compared to the placebo group.
      Additionally, some improvement in obsessive-compulsive symptoms was noted in both
      groups after the treatment, but it resulted in a more pronounced decrease in
      automaticity of drinking and aspects of craving in the gabapentin group than in
      the placebo group. CONCLUSION: Gabapentin reduces alcohol consumption and
      craving, which may help patients to maintain abstinence. These results, together
      with the virtual absence of side effects and a favorable safety profile, support
      gabapentin as a potential drug for the treatment of alcohol withdrawal and
      dependence.

PMID- 18052563
TI  - Antidepressant medication treatment failure does not predict lower remission with
      ECT for major depressive disorder: a report from the consortium for research in
      electroconvulsive therapy.
AB  - OBJECTIVE: To test whether antidepressant medication treatment failure predicts
      differential remission with electroconvulsive therapy (ECT) in nonpsychotic
      unipolar depression. METHOD: Depressed patients diagnosed with the Structured
      Clinical Interview for DSM-IV receiving ECT were assessed for medication use with
      the Antidepressant Treatment History Form (ATHF) (N = 345). Response to ECT was
      assessed with the 24-item Hamilton Rating Scale for Depression. Baseline
      medication treatment failure was analyzed as a possible predictor of remission
      status. Dates of study enrollment were from May 1997 to July 2004. RESULTS:
      Resistance to antidepressant medication as assessed by the ATHF, either taken as
      a whole or for any individual class of medication, was not predictive of acute
      remission status with ECT. CONCLUSION: Treatment failure with anti-depressant
      medication does not predict acute remission status with ECT for nonpsychotically
      depressed patients.

PMID- 18052564
TI  - Efficacy and safety of duloxetine 60 mg once daily in the treatment of pain in
      patients with major depressive disorder and at least moderate pain of unknown
      etiology: a randomized controlled trial.
AB  - OBJECTIVE: Experience of pain in major depressive disorder (MDD) can complicate
      diagnosis and impair treatment outcomes. This study evaluated the efficacy and
      safety of duloxetine in the treatment of patients with moderate pain associated
      with depression. METHOD: In this double-blind, placebo-controlled, 8-week study,
      conducted from May 2005 to May 2006, outpatients 18 years of age or older,
      presenting with major depressive disorder (DSM-IV criteria; Montgomery-Asberg
      Depression Rating Scale [MADRS] score >or= 20), moderate pain (Brief Pain
      Inventory-Short Form [BPI-SF] average pain score >or= 3), and Clinical Global
      Impressions-Severity of Illness scale (CGI-S) score >or= 4 were randomly assigned
      to either placebo (N = 165) or duloxetine 60 mg (N = 162) once daily. Primary
      outcome was change in item 5 score (average pain in the last 24 hours) of the BPI
      SF from baseline. Secondary measures were MADRS total score, other BPI-SF items,
      CGI-S, CGI-Improvement scale, Patient Global Impressions-Improvement scale,
      Symptom Checklist-90-Revised, response and remission rates, safety, and
      tolerability. RESULTS: Duloxetine, compared with placebo, significantly reduced
      pain and improved depression with significant mean changes at endpoint in both
      BPI-SF average pain scores (-2.57 vs. -1.64, p < .001) and in MADRS total scores
      (-16.69 vs. -11.31, p < .001). Remission of MDD and response rates in pain and
      MDD were significantly (p <or= .001) higher in duloxetine-treated patients.
      Duloxetine separated from placebo on most secondary outcome measures including
      the BPI-SF interference with daily life due to pain. Treatment-emergent adverse
      events (>or= 10%) in duloxetine-treated patients were nausea, hyperhidrosis, and
      dry mouth. CONCLUSION: These results support duloxetine's efficacy and
      tolerability in the treatment of pain and depression in patients with at least
      moderate pain associated with depression. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier NCT00191919 (http://www.clinicaltrials.gov).

PMID- 18052565
TI  - Clinical characteristics and psychiatric comorbidity of pyromania.
AB  - BACKGROUND: There have been few systematic studies of individuals with pyromania,
      and this paucity of research has hindered our understanding and treatment of this
      disorder. This study details the demographic and phenomenological features of
      individuals with DSM-IV lifetime pyromania. METHOD: Twenty-one adult and
      adolescent subjects (recruited from inpatient and outpatient studies of impulse
      control disorders) with lifetime DSM-IV pyromania were administered a semi
      structured interview to elicit demographic data and information on the
      phenomenology, age at onset, and associated features of the disorder. Data were
      collected from October 2003 to September 2006. RESULTS: Twenty-one subjects (10
      female [47.6%]) with lifetime pyromania (mean +/- SD age = 26.1 +/- 11.8 years;
      range, 15-49 years) were studied. The mean +/- SD age at onset for pyromania was
      18.1 +/- 5.8 years. Eighteen subjects (85.7%) reported urges to set fires.
      Subjects reported a mean +/- SD frequency of setting 1 fire every 5.9 +/- 3.8
      weeks. Much of the fire setting did not meet the legal definition of arson.
      Thirteen (61.9%) had a current comorbid Axis I mood disorder, and 10 (47.6%) met
      criteria for a current impulse-control disorder. CONCLUSION: Pyromania appears to
      be associated with high rates of psychiatric comorbidity. Research is needed to
      optimize patient care for individuals with this disorder.

PMID- 18052566
TI  - Improvement in subjective sleep in major depressive disorder with a novel
      antidepressant, agomelatine: randomized, double-blind comparison with
      venlafaxine.
AB  - OBJECTIVE: Patients with major depressive disorder (MDD) experience sleep
      disturbances that may be worsened by some antidepressant drugs early in
      treatment. The aim of this study was to assess the subjective quality of sleep of
      patients receiving agomelatine, a new antidepressant with melatonergic MT(1) and
      MT(2) receptor agonist and 5-HT(2C) antagonist properties, compared with that of
      patients receiving venlafaxine, a serotonin-norepinephrine reuptake inhibitor.
      METHOD: This double-blind, randomized study involved 332 patients with MDD (DSM
      IV criteria), lasted 6 weeks, and compared the effects of agomelatine 25-50
      mg/day and venlafaxine 75-150 mg/day, with a possible dose adjustment at 2 weeks.
      Subjective sleep was assessed with the Leeds Sleep Evaluation Questionnaire
      (LSEQ), and the main efficacy criterion was the "getting to sleep" score.
      Antidepressant efficacy was assessed with the 17-item Hamilton Rating Scale for
      Depression (HAM-D) and the Clinical Global Impressions (CGI) global improvement
      scale. The study was performed between November 2002 and June 2004. RESULTS:
      After 6 weeks, the antidepressant efficacy of agomelatine was similar to that of
      venlafaxine. The LSEQ "getting to sleep" score was significantly better with
      agomelatine (70.5 +/- 16.8 mm) than with venlafaxine (64.1 +/- 18.2 mm); the
      between-treatment difference at the last visit was 6.36 mm (p = .001), and the
      difference was already significant at week 1. Secondary sleep items, including
      LSEQ quality of sleep (p = .021), sleep awakenings (p = .040), integrity of
      behavior (p = .024), and sum of HAM-D items 4, 5, and 6 (insomnia score) (p =
      .044), were also significantly improved compared to venlafaxine, as was the CGI
      global improvement score (p = .016). Incidence of adverse events was 52.1% with
      agomelatine and 57.1% with venlafaxine, and withdrawals due to adverse events
      were more common with venlafaxine than with agomelatine (13.2% vs. 4.2%).
      CONCLUSION: Agomelatine showed similar antidepressant efficacy with earlier and
      greater efficacy in improving subjective sleep than venlafaxine in MDD patients.

PMID- 18052567
TI  - A 12-week randomized clinical trial to evaluate metabolic changes in drug-naive,
      first-episode psychosis patients treated with haloperidol, olanzapine, or
      risperidone.
AB  - OBJECTIVE: This study examined the main metabolic side effects induced by
      antipsychotic treatment in a cohort of first-episode drug-naive subjects. METHOD:
      A randomized, open-label, prospective clinical trial was conducted. Participants
      were 145 consecutive subjects included in a first-episode psychosis program
      (PAFIP) from February 2002 to February 2005, experiencing their first episode of
      psychosis (DSM-IV codes 295, 297, and 298), and never treated with antipsychotic
      medication. Patients were assigned to haloperidol, olanzapine, or risperidone
      treatment during 12 weeks. The main outcome measures were changes at 12 weeks in
      body weight; body mass index; and 12-hours-fasting morning levels of total
      cholesterol, tri-glycerides, low-density lipoprotein (LDL) cholesterol, high
      density lipoprotein cholesterol, glucose, homeostasis model assessment (HOMA)
      index, and insulin. RESULTS: At the endpoint, 128 patients were evaluated
      (88.3%). The mean doses were haloperidol = 4.2 mg/day, olanzapine = 12.7 mg/day,
      and risperidone = 3.6 mg/day. A significant weight gain was observed with the 3
      antipsychotics: haloperidol = 3.8 (SD = 4.9) kg, olanzapine = 7.5 (SD = 5.1) kg,
      and risperidone = 5.6 (SD = 4.5) kg. Metabolic parameters showed a worsening
      lipid profile with the 3 treatments (statistically significant increase in total
      cholesterol and LDL cholesterol levels). Only the olanzapine group showed
      significant increases in triglyceride levels. After the 12-week study period,
      there were no significant changes in parameters involving glucose metabolism for
      any group. CONCLUSIONS: Drug-naive patients experienced an extraordinary weight
      gain with first- and second-generation antipsychotics after the first 12 weeks of
      treatment. Significant increases in total cholesterol and LDL cholesterol levels
      are associated with the 3 treatments. Weight gain and metabolic disturbances
      induced by antipsychotics may increase the risk of developing cardiovascular
      disease.

PMID- 18052568
TI  - Suicidal behavior in obsessive-compulsive disorder.
AB  - OBJECTIVE: There are limited data on suicidal behavior in obsessive-compulsive
      disorder (OCD). This study examines suicidal behavior and its clinical correlates
      in OCD subjects. METHOD: One hundred consecutive DSM-IV OCD subjects attending
      the specialty OCD clinic and the inpatient services of a major psychiatric
      hospital in India from November 1, 2003, to October 31, 2004, formed the sample
      of this study. Subjects were assessed systematically by using structured
      interviews and various rating scales. The Scale for Suicide Ideation-worst ever
      (lifetime) and -current measured suicidal ideation. The 24-item Hamilton Rating
      Scale for Depression (HAM-D) measured severity of depression, and the Beck
      Hopelessness Scale (BHS) measured hopelessness. We performed assessments at study
      entry. We employed binary logistic regression (Wald) forward stepwise analysis
      for prediction of suicidal ideation and suicide attempt, and we used structural
      equation modeling for identifying the potential factors contributing to suicidal
      ideation. RESULTS: The rates of suicidal ideation, worst ever and current, were
      59% and 28%, respectively. History of suicide attempt was reported in 27% of the
      subjects. For past suicide attempt, worst ever suicidal ideation (p < .001) was
      the only significant predictor, with an overall prediction of 89%, and accounted
      for 60% of the variance. For worst ever suicidal ideation, major depression (p =
      .043), HAM-D score (p = .013), BHS score (p = .011), and history of attempt (p =
      .009) were significant predictors, with an overall prediction of 82% and variance
      of 56%. Somewhat similar predictors emerged as significant for current suicidal
      ideators, with an overall prediction of 85% and variance of 50%. In the
      structural equation model, too, presence of depression and high BHS score
      contributed to suicidal ideation. CONCLUSIONS: OCD is associated with a high risk
      for suicidal behavior. Depression and hopelessness are the major correlates of
      suicidal behavior. It is vital that patients with OCD undergo detailed assessment
      for suicide risk and associated depression. Aggressive treatment of depression
      may be warranted to modify the risk for suicide. Future studies should examine
      suicidal behavior in a prospective design in larger samples to examine if
      severity of OCD and treatment nonresponse contribute to suicide risk.

PMID- 18052569
TI  - The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia:
      2006 update.
AB  - BACKGROUND: A panel of academic psychiatrists and pharmacists, clinicians from
      the Texas public mental health system, advocates, and consumers met in June 2006
      in Dallas, Tex., to review recent evidence in the pharmacologic treatment of
      schizophrenia. The goal of the consensus conference was to update and revise the
      Texas Medication Algorithm Project (TMAP) algorithm for schizophrenia used in the
      Texas Implementation of Medication Algorithms, a statewide quality assurance
      program for treatment of major psychiatric illness. METHOD: Four questions were
      identified via premeeting teleconferences. (1) Should antipsychotic treatment of
      first-episode schizophrenia be different from that of multiepisode schizophrenia?
      (2) In which algorithm stages should first-generation antipsychotics (FGAs) be an
      option? (3) How many antipsychotic trials should precede a clozapine trial? (4)
      What is the status of augmentation strategies for clozapine? Subgroups reviewed
      the evidence in each area and presented their findings at the conference.
      RESULTS: The algorithm was updated to incorporate the following recommendations.
      (1) Persons with first-episode schizophrenia typically require lower
      antipsychotic doses and are more sensitive to side effects such as weight gain
      and extrapyramidal symptoms (group consensus). Second-generation antipsychotics
      (SGAs) are preferred for treatment of first-episode schizophrenia (majority
      opinion). (2) FGAs should be included in algorithm stages after first episode
      that include SGAs other than clozapine as options (group consensus). (3) The
      recommended number of trials of other antipsychotics that should precede a
      clozapine trial is 2, but earlier use of clozapine should be considered in the
      presence of persistent problems such as suicidality, comorbid violence, and
      substance abuse (group consensus). (4) Augmentation is reasonable for persons
      with inadequate response to clozapine, but published results on augmenting agents
      have not identified replicable positive results (group consensus). CONCLUSIONS:
      These recommendations are meant to provide a framework for clinical decision
      making, not to replace clinical judgment. As with any algorithm, treatment
      practices will evolve beyond the recommendations of this consensus conference as
      new evidence and additional medications become available.

PMID- 18052572
TI  - A systematic review of rates and diagnostic validity of comorbid adult attention
      deficit/hyperactivity disorder and bipolar disorder.
AB  - OBJECTIVE: Adult attention-deficit/hyperactivity disorder (ADHD) is increasingly
      recognized and reported to frequently coexist with bipolar disorder. Concurrent
      diagnosis of adult ADHD and bipolar disorder remains controversial. In this
      study, we conducted a systematic review to examine the rates and diagnostic
      validity of the concept of comorbid adult ADHD and bipolar disorder. DATA
      SOURCES: MEDLINE, Embase, PsycInfo, and Cochrane databases were searched for
      articles published before March 30, 2007, using the keywords manic, bipolar,
      attention deficit hyperactivity, and adult. The computer search was supplemented
      with bibliographic cross-referencing. STUDY SELECTION: Exclusion criteria were
      studies with only pediatric subjects, childhood ADHD only but not adult ADHD, and
      either bipolar disorder or ADHD only, but not both; review articles, case
      reports; letters to the editor; and book chapters. Of the 262 citations found, 12
      studies met our inclusion criteria. DATA EXTRACTION: Specific diagnostic
      validating criteria examined were phenomenology, course of illness, heredity,
      biological markers, and treatment response. There were 6 studies on comorbid
      rates, 4 on phenomenology, 3 on course of illness, 2 on heredity, none on
      biological markers, and 1 on treatment response. DATA SYNTHESIS: The proposed
      comorbid syndrome is fairly common (present in up to 47% of adult ADHD and 21% of
      bipolar disorder populations), with a more severe course of illness compared with
      that of bipolar disorder alone, and high rates of comorbidity with other
      psychiatric disorders. Its treatment appears to require initial mood
      stabilization. CONCLUSIONS: Comorbid adult ADHD and bipolar disorder has been
      insufficiently studied, with more emphasis on comorbidity rates and few data on
      course, neurobiology, heredity, and treatment. The diagnostic validity of adult
      ADHD/ bipolar disorder as a true comorbidity is not well-established on the basis
      of this equivocal and insufficient literature. More studies are greatly needed to
      further clarify its diagnostic validity and treatment approach.

PMID- 18052570
TI  - Maintenance treatment with risperidone or low-dose haloperidol in first-episode
      schizophrenia: 1-year results of a randomized controlled trial within the German
      Research Network on Schizophrenia.
AB  - OBJECTIVE: Second-generation antipsychotics (SGAs) have proven superior to first
      generation antipsychotics regarding relapse prevention, mainly in multiple
      episode patients. Practice guidelines recommend SGAs as first-line treatment
      particularly in first-episode patients, although evidence for this group is still
      limited. Accordingly, the hypothesis of whether 1-year relapse rate in first
      episode schizophrenia under maintenance treatment with risperidone is lower
      compared to haloperidol in low dose was tested. METHOD: Between November 2000 and
      May 2004, 1372 patients had been screened for eligibility in the inpatient
      facilities of 13 German psychiatric university hospitals. 159 remitted patients
      were enrolled after treatment of an acute first episode of schizophrenia
      according to ICD-10 F20 criteria. In the randomized controlled trial, double
      blind antipsychotic treatment with risperidone or haloperidol was maintained in a
      targeted dose of 2 to 4 mg/day for 1 year. 151 patients were eligible for
      analysis. For 127 patients, this was a continuation trial after 8 weeks of
      randomized, double-blind, acute treatment with the same drugs; 24 patients were
      additionally randomly assigned after open acute treatment. RESULTS: With both
      antipsychotics (risperidone, N = 77; haloperidol, N = 74), no relapse evolved.
      Additionally, according to 2 post hoc defined measures of "marked clinical
      deterioration," significant differences occurred neither in the 2 respective
      deterioration rates (risperidone = 9%/23%; haloperidol = 8%/22%) nor in time
      until deterioration. Both antipsychotics were equally effective regarding
      significant symptom reduction and improvement in quality of life. Extrapyramidal
      symptoms were slightly higher with haloperidol. The overall dropout rate of 68%,
      however, was not significantly different between the 2 drug groups. CONCLUSION:
      Against the background of an overall favorable outcome, the hypothesized
      difference between risperidone and low-dose haloperidol regarding relapse
      prevention could not be supported for this sample of patients with first-episode
      schizophrenia. Possible design-related reasons for this finding are discussed.
      With regard to the high dropout rate, special programs are needed to keep
      schizophrenia patients who are in their early acute and postacute illness course
      in effective and safe treatment. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov
      identifier: NCT00159081.

PMID- 18052573
TI  - Comparison of antidepressant use between subjects with bipolar disorder and major
      depressive disorder with or without comorbid anxiety.
AB  - OBJECTIVE: Antidepressants are recommended for the treatment of depressive and
      anxiety symptoms in patients with major depressive disorder, but caution is urged
      when used for the treatment of these symptoms in bipolar disorder. It is not
      known whether these differing recommendations are reflected in clinical practice,
      as comparative analyses of rates of antidepressant use between bipolar disorder
      and major depressive disorder subjects with or without comorbid anxiety have not
      been reported. METHOD: Data source was the Canadian Community Health Survey on
      Mental Health and Well-Being, a large, representative mental health survey
      conducted from May to December 2002. Rates of antidepressant use were compared
      for subjects with bipolar disorder according to the World Mental Health-Composite
      International Diagnostic Interview or major depressive disorder according to DSM
      IV criteria, with or without comorbid anxiety (DSM-IV). The independent effects
      of the diagnostic group and of a comorbid anxiety disorder were determined by
      controlling for sociodemographic and clinical variables using logistic
      regression. RESULTS: Rate of antidepressant use was significantly higher among
      all subjects with bipolar disorder (N = 756) compared with all subjects with
      major depressive disorder (N = 3863) (27.2% vs. 23.1%, p = .02), but this
      difference was no longer significant when other factors were controlled for in
      the regression analysis. With the major depressive disorder without anxiety group
      as the reference, the likelihood of antidepressant use was significantly higher
      in both the bipolar disorder with anxiety group (OR = 1.83, 95% CI = 1.02 to
      3.27, p = .04) and the major depressive disorder with anxiety group (OR = 1.45,
      95% CI = 1.00 to 2.09, p = .05). CONCLUSION: After sociodemographic and clinical
      variables were controlled for, similar rates of antidepressant use were
      identified among bipolar disorder and major depressive disorder subjects. Further
      efforts are needed to enhance screening for bipolar disorder among depressed
      patients and to re-examine the risk/benefit analysis of antidepressants for
      bipolar disorder patients in light of emerging alternatives. Significantly
      increased rates of antidepressant use in subjects with a comorbid anxiety
      disorder suggest that anxiety symptoms may be a key reason why physicians are
      choosing to prescribe antidepressants for patients with bipolar disorder and
      major depressive disorder.

PMID- 18052574
TI  - Effect of olanzapine, risperidone, and haloperidol treatment on weight and body
      mass index in first-episode schizophrenia patients in India: a randomized, double
      blind, controlled, prospective study.
AB  - OBJECTIVE: The presence of obesity and increases in body mass are important risk
      factors for cardiovascular disease and diabetes. This study examined the effects
      of olanzapine, risperidone, and haloperidol on weight, body mass index (BMI), and
      development of obesity in a drug-naive population compared with a matched healthy
      control group. METHOD: Consecutive patients during the period from June through
      October 2006 with DSM-IV schizophrenia at our referral psychiatric hospital were
      recruited for an extensive prospective study that included anthropometric
      measures of weight, waist circumference, waist-hip ratio, and BMI. Subjects were
      randomly assigned to receive haloperidol, olanzapine, or risperidone and compared
      with a matched healthy control group. The prevalence of obesity, which was the
      main outcome measure, was assessed on the basis of 2 criteria: revised World
      Health Organization (WHO) definition for Asians and criteria of the International
      Diabetes Federation (IDF). Inclusions started in June 2006, and patients were
      followed for a period of 6 weeks. RESULTS: The analysis of 66 patients showed a
      prevalence of overweight (WHO criteria) at 22.7% and obesity at 31.8% (IDF
      criteria). The prevalence of obesity (IDF criteria) in our patients is over 30
      times as high as that of the matched healthy control group (p < .001). Subjects
      in the olanzapine group had the greatest weight gain at 5.1 kg, followed by
      risperidone at 4.1 kg and haloperidol at 2.8 kg. CONCLUSIONS: Obesity is highly
      prevalent among patients treated with atypical antipsychotics for schizophrenia.
      Assessment and monitoring of obesity along with preventive and curative measures
      should be part of the clinical management of patients treated with
      antipsychotics. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00534183,
      www.clinicaltrials.gov.

PMID- 18052575
TI  - The roadmap for antipsychotic psychopharmacology: an overview.

PMID- 18052576
TI  - Teaching and practicing psychopharmacology.

PMID- 18052577
TI  - Are you analyzing me?

PMID- 18052579
TI  - Response to self-injurious behaviors in a community sample of young women.

PMID- 18052580
TI  - Aripiprazole and perphenazine: no difference.

PMID- 18052582
TI  - A case of aripiprazole-related tardive akathisia and its treatment with
      ropinirole.

PMID- 18052583
TI  - Aripiprazole treatment of patients with borderline personality disorder.

PMID- 18052588
TI  - Stent-graft deployment to treat a perigraft seroma formed after descending
      thoracic aortic surgery.
AB  - PURPOSE: To report a case of stent-graft implantation for a perigraft seroma that
      formed after descending thoracic aortic surgery. CASE REPORT: A 70-year-old woman
      presented with a perigraft seroma after a descending thoracic aortic surgery 10
      years ago in which a polytetrafluoroethylene graft was used. Chest radiography
      and computed tomography confirmed the presence of a large perigraft seroma. The
      previous graft was covered with a stent-graft to decrease graft porosity. At 1
      year, postoperative examinations revealed a decrease in the size of the perigraft
      seroma. CONCLUSION: Stent-graft implantation could prove useful in cases of
      perigraft seromas where additional conventional surgery may pose difficulties.

PMID- 18052589
TI  - Current state of dynamic imaging in endovascular aortic aneurysm repair.
AB  - Dynamic imaging, in which the time dimension has a specific function in data
      (image) interpretation, is becoming increasingly important when contemplating
      endovascular aneurysm repair. Clinical parameters and complications, including
      proper sizing, successful aneurysm sac exclusion, optimal stent-graft design,
      endoleaks, graft migration, and stent fracture are beginning to be better
      understood through dynamic magnetic resonance, ultrasound, and dynamic computed
      tomography. The current practice using static 3-dimensional reconstructions for
      the planning and follow-up of aortic aneurysm endograft treatment will most
      likely evolve, and the use of dynamic aortic imaging will continue to increase.
      Validation of these imaging modalities in larger scale trials is needed.

PMID- 18052590
TI  - Cryoplasty therapy for limb salvage in patients with critical limb ischemia.
AB  - PURPOSE: To report the 6-month outcomes from a prospective multicenter study
      investigating the use of cryoplasty (cold balloon angioplasty) to treat below
      knee occlusive disease in patients with critical limb ischemia (CLI). METHODS:
      Between August 2004 and October 2005, 108 patients (77 men; mean age 73+/-12
      years, range 41-101) with CLI involving 111 limbs were enrolled in a prospective
      multicenter trial (Below-the-Knee Chill Study), which was conducted at 16
      institutions. The primary study endpoints were acute technical success, defined
      as the ability to achieve < or =50% residual stenosis and continuous inline flow
      to the foot, and absence of major (above or below-knee) amputation of the target
      limb 180 days post procedure. RESULTS: Acute technical success was achieved in
      108 (97.3%) of the 111 limbs treated, with only 1 (0.9%) clinically significant
      dissection (> or =type C) and 2 residual stenoses >50%. During the 180-day follow
      up, 15 (13.9%) of the initial 108 patients either withdrew or were lost to follow
      up. Five (4.6%) deaths occurred, leaving 88 (81.5%) patients with 91 (82.0%)
      treated limbs available for 180-day assessment. The rate of freedom from major
      amputation at 180 days was 93.4%. Amputation-free survival was 89.3% at 180 days
      (5 deaths, 6 major amputations). Stratifying data by diabetics (n=71) versus non
      diabetics (n=34), the 180-day death and amputation rates were 4.9% and 10.0%,
      respectively, for diabetics versus 6.7% and 0.0%, respectively, for non
      diabetics. CONCLUSION: Cryoplasty therapy is a safe and effective method of
      treating infrapopliteal disease, providing excellent acute outcomes and a high
      rate of limb salvage in patients with CLI. Study outcomes support the use of
      cryoplasty therapy as a primary treatment option for patients with CLI secondary
      to below- knee disease.

PMID- 18052591
TI  - Endovascular repair of ascending aortic pseudoaneurysm: technical considerations
      of a common carotid artery approach using the Zenith aortic cuff endograft.
AB  - PURPOSE: To present a technique for endovascular treatment using Zenith aortic
      cuff extenders delivered via a left common carotid artery (CCA) approach in a
      patient with a large symptomatic ascending aortic pseudoaneurysm. CASE REPORT: A
      78-year-old man with recent stroke developed worsening exertional dyspnea and
      chest pain 4 years following coronary artery bypass grafting. Imaging
      demonstrated a bovine arch and an 8-x12-cm ascending aortic pseudoaneurysm that
      was compressing the pulmonary arteries. The treatment strategy was to deliver a
      Zenith aortic cuff to seal the ascending aortic pseudoaneurysm via a left CCA
      approach. With the patient under general anesthesia, the left CCA was exposed and
      a transverse arteriotomy was made to introduce the Zenith aortic cuff sheath; the
      distal CCA was clamped to prevent catheter-related embolization. With its
      nosecone removed, a 32-x36-mm Zenith aortic cuff was delivered to the ascending
      aorta via the left CCA and positioned under transient cardiac arrest initiated
      with intravenous adenosine. A total of 3 Zenith aortic cuffs were placed in the
      ascending aorta to successfully exclude the pseudoaneurysm. The patient tolerated
      the procedure well; follow-up imaging showed successful pseudoaneurysm exclusion
      without endoleak. CONCLUSION: Ascending aortic pseudoaneurysm is a formidable
      clinical challenge due in part to the significant operative stress in a
      conventional surgical repair, as well as limited endovascular treatment options.
      Because there are no approved endovascular devices for ascending aortic aneurysm
      repair, clinicians may have to rely on endograft components designed for
      abdominal aortic aneurysms to treat lesions in the ascending aorta.

PMID- 18052592
TI  - Endovascular repair in the ascending aorta: stretching the limits of current
      technology.

PMID- 18052593
TI  - Emergency abdominal aortic aneurysm repair with a preferential endovascular
      strategy: mortality and cost-effectiveness analysis.
AB  - PURPOSE: To assess mortality and treatment costs of a new management protocol
      with preferential use of emergency endovascular aneurysm repair (eEVAR) for acute
      abdominal aortic aneurysm (AAA). METHODS: From September 2003 until February
      2005, 49 consecutive patients (45 men; mean age 71 years) with acute AAA were
      entered into a prospective study of a new management protocol that featured
      preferential use of eEVAR (n=18); patients with unsuitable anatomy or who were
      hemodynamically unstable underwent open repair (n=31). Mortality data and costs
      of treatment were compared in this mixed prospective group to a historical
      control group consisting of 147 patients (128 men; mean age 71 years) who
      underwent open repair from January 1998 to December 2001. All direct medical
      costs were included from the moment of admission until discharge from the
      hospital. RESULTS: Mortality in the mixed prospective group (18%) was lower than
      in the historical control group (31%), but the difference did not reach
      statistical significance (p=0.099). The mean total cost in the mixed prospective
      group was 17,164 euro compared to 21,084 euro in the historical open repair group
      (p=0.255). CONCLUSION: A preferential eEVAR protocol for acute AAA can decrease
      mortality and does not increase overall costs during initial treatment, but
      larger studies are needed to determine if these trends are statistically
      significant.

PMID- 18052594
TI  - Subintimal angioplasty of an aortoiliac occlusion: re-entry site created using a
      transseptal needle under intravascular ultrasound guidance.
AB  - PURPOSE: To report the use of a transseptal needle to cross the intimal flap in
      subintimal angioplasty of a flush aortoiliac occlusion via a retrograde approach.
      CASE REPORT: A 53-year-old man with claudication of the right lower limb and an
      angiographically documented right aortoiliac occlusion was treated with
      subintimal angioplasty via an ipsilateral retrograde approach. After puncture of
      the right common femoral artery, a 0.035-inch hydrophilic guidewire was advanced
      via the subintimal space toward the aortic true lumen, but the wire could not re
      enter the true lumen. A transseptal needle was used to puncture the intimal flap
      under intravascular ultrasound (IVUS) guidance. Angioplasty/stenting was
      performed successfully, and the patient's symptoms were relieved. Computed
      tomography at 15 months revealed patent stents. CONCLUSION: The use of a
      transseptal needle to cross the intimal flap in total aortoiliac occlusions is
      technically feasible under IVUS guidance and enables successful angioplasty.

PMID- 18052595
TI  - Hydrogel-mediated release of basic fibroblast growth factor from a stent-graft
      accelerates biological fixation with the aortic wall in a porcine model.
AB  - PURPOSE: To evaluate the local reaction of the aortic wall induced by basic
      fibroblast growth factor (bFGF) released from a gelatin hydrogel coated on the
      outer surface of a stent-graft for the purpose of biological fixation. METHODS: A
      total of 18 nitinol-based, polyester-covered stent-grafts were implanted in 6
      porcine aortas for 1 month. The implanted stent-grafts were divided into 3
      groups: the control group (uncoated), the hydrogel group (coated with hydrogel
      containing water), and the bFGF group (coated with hydrogel containing bFGF).
      After stent-graft implantation, the results of intravascular ultrasound (IVUS)
      and qualitative and quantitative microscopic examinations were compared among the
      groups. RESULTS: In the bFGF group, a thin white lamellar tissue was observed on
      IVUS images. Significantly more new intimal tissue formation was observed in all
      the bFGF group animals than in the other 2 groups, and alpha smooth muscle (SM)
      actin-positive cells (alphaSMCs) were detected in this new tissue. The alphaSMCs
      within the fabric of tightly woven grafts were significantly more abundant in the
      bFGF group than in the other groups. CONCLUSION: The local controlled release of
      bFGF from the stent-graft significantly accelerated the proliferation of new
      intimal tissue between the aorta and the stent-graft and within the graft
      materials. These findings suggest that a graft can be fixed biologically to the
      aortic wall, which may contribute to the shrinkage of aneurysms following stent
      grafting.

PMID- 18052596
TI  - A prospective clinical, economic, and quality-of-life analysis comparing
      endovascular aneurysm repair (EVAR), open repair, and best medical treatment in
      high-risk patients with abdominal aortic aneurysms suitable for EVAR: the Irish
      patient trial.
AB  - PURPOSE: To report the results of a trial comparing endovascular aneurysm repair
      (EVAR) to open repair (OR) and best medical therapy (BMT) involving high-risk
      patients with abdominal aortic aneurysms (AAA) suitable for EVAR. METHODS: From
      2002 to 2007, 1083 patients with aortic aneurysm disease were referred to a
      tertiary care university hospital. Of these, 162 (119 men; mean age 76 years)
      were high-risk patients with AAAs anatomically suitable for EVAR. Following
      comprehensive consultation with the patient, the family, and the primary
      physician, elective treatment was selected: OR (n=52), EVAR (n=66), or BMT
      (n=44). Outcomes were compared using Kaplan-Meier survival analyses and a
      parameter that measured the quality time spent without symptoms of disease or
      toxicity of treatment (Q-TWIST). RESULTS: Four-year freedom from aneurysm-related
      death following EVAR (96.7%) was markedly better compared to BMT (66.8%; p=0.002)
      and was similar to OR (93.9%, p=0.483). Four-year freedom from major adverse
      clinical events was significantly better with EVAR (78%) compared with BMT (28%;
      p=0.001) and was equivalent to OR (75%; p=0.519). The 4-year intervention-free
      survival rate for EVAR (95%) almost matched OR (98%; p=0.410). At 4 years, Q
      TWIST was 3.64 years for EVAR patients, 3.60 years for OR, and 2.22 years for
      BMT. Q-TWIST significantly improved with EVAR compared to OR (p<0.003). In the
      cost analysis, 52 high-risk patients were treated with OR over the 5-year period
      (2002-2007) at a total inpatient cost of 1,257,457 euro. The 66 patients treated
      with EVAR (14 patients more than OR) incurred a lower cost of 1,129,138 euro.
      Including the cost of follow-up over 4 years, the mean cost per patient was
      18,476 euro for EVAR and 24,252 euro for OR, a savings of 5,776 euro per patient
      treated with EVAR. CONCLUSION: In high-risk patients, EVAR reduces aneurysm
      related death compared to BMT. Equated to the gold standard of open repair, EVAR,
      as a "one-time procedure," substantially reduces operative morbidity, hospital
      stay, costs, and utilization of intensive care facilities if performed in a high
      volume center.

PMID- 18052597
TI  - Aortitis following percutaneous aortic side branch embolization prior to
      endovascular repair of infrarenal aortic aneurysm.
AB  - PURPOSE: To report two cases of life-threatening aortic infection after
      percutaneous endovascular coil embolization prior to endovascular abdominal
      aortic aneurysm (AAA) repair (EVAR). CASE REPORT: Two 76-year-old patients were
      readmitted 5 days and 3 weeks, respectively, after technically successful
      percutaneous coil embolization of aortic side branches in advance of scheduled
      EVAR. In the first patient, the right hypogastric artery, the inferior mesenteric
      artery (IMA), and a lumbar artery had been embolized, whereas in the second
      patient only the right hypogastric artery and the IMA had been occluded. On
      admission, both patients presented with severe abdominal pain. Investigations
      revealed acute aortic infection in both patients, combined with substantial AAA
      enlargement in one. Open surgical infrarenal aortic replacement was performed
      using homografts, and antibiotic therapy was initiated. After uneventful
      recovery, both patients were asymptomatic, had intact aortic homografts, and
      showed no evidence of infection after 12 and 18 months of follow-up,
      respectively. CONCLUSION: Endovascular infections are a potentially serious
      complication following percutaneous coil embolization of major aortic branches.
      Early diagnosis and dedicated therapy are mandatory. Immediate resection of the
      infected aorta and replacement with homografts in association with prolonged
      antibiotic treatment showed good midterm results.

PMID- 18052598
TI  - Infections after endovascular coil embolization.

PMID- 18052599
TI  - Chimney grafts and bare stents: aortic branch preservation revisited.

PMID- 18052600
TI  - Cytomegalovirus retinitis: the neglected disease of the AIDS pandemic.

PMID- 18052601
TI  - N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine
      and nevirapine resistance.
AB  - BACKGROUND: The catalytically active 66-kDa subunit of the human immunodeficiency
      virus type 1 (HIV-1) reverse transcriptase (RT) consists of DNA polymerase,
      connection, and ribonuclease H (RNase H) domains. Almost all known RT inhibitor
      resistance mutations identified to date map to the polymerase domain of the
      enzyme. However, the connection and RNase H domains are not routinely analysed in
      clinical samples and none of the genotyping assays available for patient
      management sequence the entire RT coding region. The British Columbia Centre for
      Excellence in HIV/AIDS (the Centre) genotypes clinical isolates up to codon 400
      in RT, and our retrospective statistical analyses of the Centre's database have
      identified an N348I mutation in the RT connection domain in treatment-experienced
      individuals. The objective of this multidisciplinary study was to establish the
      in vivo relevance of this mutation and its role in drug resistance. METHODS AND
      FINDINGS: The prevalence of N348I in clinical isolates, the time taken for it to
      emerge under selective drug pressure, and its association with changes in viral
      load, specific drug treatment, and known drug resistance mutations was analysed
      from genotypes, viral loads, and treatment histories from the Centre's database.
      N348I increased in prevalence from below 1% in 368 treatment-naive individuals to
      12.1% in 1,009 treatment-experienced patients (p = 7.7 x 10(-12)). N348I appeared
      early in therapy and was highly associated with thymidine analogue mutations
      (TAMs) M41L and T215Y/F (p < 0.001), the lamivudine resistance mutations M184V/I
      (p < 0.001), and non-nucleoside RTI (NNRTI) resistance mutations K103N and
      Y181C/I (p < 0.001). The association with TAMs and NNRTI resistance mutations was
      consistent with the selection of N348I in patients treated with regimens that
      included both zidovudine and nevirapine (odds ratio 2.62, 95% confidence interval
      1.43-4.81). The appearance of N348I was associated with a significant increase in
      viral load (p < 0.001), which was as large as the viral load increases observed
      for any of the TAMs. However, this analysis did not account for the simultaneous
      selection of other RT or protease inhibitor resistance mutations on viral load.
      To delineate the role of this mutation in RT inhibitor resistance, N348I was
      introduced into HIV-1 molecular clones containing different genetic backbones.
      N348I decreased zidovudine susceptibility 2- to 4-fold in the context of wild
      type HIV-1 or when combined with TAMs. N348I also decreased susceptibility to
      nevirapine (7.4-fold) and efavirenz (2.5-fold) and significantly potentiated
      resistance to these drugs when combined with K103N. Biochemical analyses of
      recombinant RT containing N348I provide supporting evidence for the role of this
      mutation in zidovudine and NNRTI resistance and give some insight into the
      molecular mechanism of resistance. CONCLUSIONS: This study provides the first in
      vivo evidence that treatment with RT inhibitors can select a mutation (i.e.,
      N348I) outside the polymerase domain of the HIV-1 RT that confers dual-class
      resistance. Its emergence, which can happen early during therapy, may
      significantly impact on a patient's response to antiretroviral therapies
      containing zidovudine and nevirapine. This study also provides compelling
      evidence for investigating the role of other mutations in the connection and
      RNase H domains in virological failure.

PMID- 18052602
TI  - Elevated risk for HIV infection among men who have sex with men in low- and
      middle-income countries 2000-2006: a systematic review.
AB  - BACKGROUND: Recent reports of high HIV infection rates among men who have sex
      with men (MSM) from Asia, Africa, Latin America, and the former Soviet Union
      (FSU) suggest high levels of HIV transmission among MSM in low- and middle-income
      countries. To investigate the global epidemic of HIV among MSM and the
      relationship of MSM outbreaks to general populations, we conducted a
      comprehensive review of HIV studies among MSM in low- and middle-income countries
      and performed a meta-analysis of reported MSM and reproductive-age adult HIV
      prevalence data. METHODS AND FINDINGS: A comprehensive review of the literature
      was conducted using systematic methodology. Data regarding HIV prevalence and
      total sample size was sequestered from each of the studies that met inclusion
      criteria and aggregate values for each country were calculated. Pooled odds ratio
      (OR) estimates were stratified by factors including HIV prevalence of the
      country, Joint United Nations Programme on HIV/AIDS (UNAIDS)-classified level of
      HIV epidemic, geographic region, and whether or not injection drug users (IDUs)
      played a significant role in given epidemic. Pooled ORs were stratified by
      prevalence level; very low-prevalence countries had an overall MSM OR of 58.4
      (95% CI 56.3-60.6); low-prevalence countries, 14.4 (95% CI 13.8-14.9); and medium
      to high-prevalence countries, 9.6 (95% CI 9.0-10.2). Significant differences in
      ORs for HIV infection among MSM in were seen when comparing low- and middle
      income countries; low-income countries had an OR of 7.8 (95% CI 7.2-8.4), whereas
      middle-income countries had an OR of 23.4 (95% CI 22.8-24.0). Stratifying the
      pooled ORs by whether the country had a substantial component of IDU spread
      resulted in an OR of 12.8 (95% CI 12.3-13.4) in countries where IDU transmission
      was prevalent, and 24.4 (95% CI 23.7-25.2) where it was not. By region, the OR
      for MSM in the Americas was 33.3 (95% CI 32.3-34.2); 18.7 (95% CI 17.7-19.7) for
      Asia; 3.8 (95% CI 3.3-4.3) for Africa; and 1.3 (95% CI 1.1-1.6) for the low- and
      middle-income countries of Europe. CONCLUSIONS: MSM have a markedly greater risk
      of being infected with HIV compared with general population samples from low- and
      middle-income countries in the Americas, Asia, and Africa. ORs for HIV infection
      in MSM are elevated across prevalence levels by country and decrease as general
      population prevalence increases, but remain 9-fold higher in medium-high
      prevalence settings. MSM from low- and middle-income countries are in urgent need
      of prevention and care, and appear to be both understudied and underserved.

PMID- 18052603
TI  - When do HIV-infected women disclose their HIV status to their male partner and
      why? A study in a PMTCT programme, Abidjan.
AB  - BACKGROUND: In Africa, women tested for HIV during antenatal care are counselled
      to share with their partner their HIV test result and to encourage partners to
      undertake HIV testing. We investigate, among women tested for HIV within a
      prevention of mother-to-child transmission of HIV (PMTCT) programme, the key
      moments for disclosure of their own HIV status to their partner and the impact on
      partner HIV testing. METHODS AND FINDINGS: Within the Ditrame Plus PMTCT project
      in Abidjan, 546 HIV-positive and 393 HIV-negative women were tested during
      pregnancy and followed-up for two years after delivery. Circumstances, frequency,
      and determinants of disclosure to the male partner were estimated according to
      HIV status. The determinants of partner HIV testing were identified according to
      women's HIV status. During the two-year follow-up, disclosure to the partner was
      reported by 96.7% of the HIV-negative women, compared to 46.2% of HIV-positive
      women (chi(2) = 265.2, degrees of freedom [df] = 1, p < 0.001). Among HIV
      infected women, privileged circumstances for disclosure were just before
      delivery, during early weaning (at 4 mo to prevent HIV postnatal transmission),
      or upon resumption of sexual activity. Formula feeding by HIV-infected women
      increased the probability of disclosure (adjusted odds ratio 1.54, 95% confidence
      interval 1.04-2.27, Wald test = 4.649, df = 1, p = 0.031), whereas household
      factors such as having a co-spouse or living with family reduced the probability
      of disclosure. The proportion of male partners tested for HIV was 23.1% among HIV
      positive women and 14.8% among HIV-negative women (chi(2) = 10.04, df = 1, p =
      0.002). Partners of HIV-positive women who were informed of their wife's HIV
      status were more likely to undertake HIV testing than those not informed (37.7%
      versus 10.5%, chi(2) = 56.36, df = 1, p < 0.001). CONCLUSIONS: In PMTCT
      programmes, specific psychosocial counselling and support should be provided to
      women during the key moments of disclosure of HIV status to their partners (end
      of pregnancy, weaning, and resumption of sexual activity). This support could
      contribute to improving women's adherence to the advice given to prevent
      postnatal and sexual HIV transmission.

PMID- 18052604
TI  - Assessment of recent HIV-1 infection by a line immunoassay for HIV-1/2
      confirmation.
AB  - BACKGROUND: Knowledge of the number of recent HIV infections is important for
      epidemiologic surveillance. Over the past decade approaches have been developed
      to estimate this number by testing HIV-seropositive specimens with assays that
      discriminate the lower concentration and avidity of HIV antibodies in early
      infection. We have investigated whether this "recency" information can also be
      gained from an HIV confirmatory assay. METHODS AND FINDINGS: The ability of a
      line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) to distinguish recent
      from older HIV-1 infection was evaluated in comparison with the Calypte HIV-1 BED
      Incidence enzyme immunoassay (BED-EIA). Both tests were conducted prospectively
      in all HIV infections newly diagnosed in Switzerland from July 2005 to June 2006.
      Clinical and laboratory information indicative of recent or older infection was
      obtained from physicians at the time of HIV diagnosis and used as the reference
      standard. BED-EIA and various recency algorithms utilizing the antibody reaction
      to INNO-LIA's five HIV-1 antigen bands were evaluated by logistic regression
      analysis. A total of 765 HIV-1 infections, 748 (97.8%) with complete test
      results, were newly diagnosed during the study. A negative or indeterminate HIV
      antibody assay at diagnosis, symptoms of primary HIV infection, or a negative HIV
      test during the past 12 mo classified 195 infections (26.1%) as recent (< or = 12
      mo). Symptoms of CDC stages B or C classified 161 infections as older (21.5%),
      and 392 patients with no symptoms remained unclassified. BED-EIA ruled 65% of the
      195 recent infections as recent and 80% of the 161 older infections as older. Two
      INNO-LIA algorithms showed 50% and 40% sensitivity combined with 95% and 99%
      specificity, respectively. Estimation of recent infection in the entire study
      population, based on actual results of the three tests and adjusted for a test's
      sensitivity and specificity, yielded 37% for BED-EIA compared to 35% and 33% for
      the two INNO-LIA algorithms. Window-based estimation with BED-EIA yielded 41%
      (95% confidence interval 36%-46%). CONCLUSIONS: Recency information can be
      extracted from INNO-LIA-based confirmatory testing at no additional costs. This
      method should improve epidemiologic surveillance in countries that routinely use
      INNO-LIA for HIV confirmation.

PMID- 18052605
TI  - Should we include connection domain mutations of HIV-1 reverse transcriptase in
      HIV resistance testing.

PMID- 18052606
TI  - HIV treatment proceeds as prevention research confounds.

PMID- 18052607
TI  - Antibody-based HIV-1 vaccines: recent developments and future directions.

PMID- 18052608
TI  - Filling in the gaps: artistic license in education and outreach.

PMID- 18052609
TI  - Incomplete and inaccurate vocal imitation after knockdown of FoxP2 in songbird
      basal ganglia nucleus Area X.
AB  - The gene encoding the forkhead box transcription factor, FOXP2, is essential for
      developing the full articulatory power of human language. Mutations of FOXP2
      cause developmental verbal dyspraxia (DVD), a speech and language disorder that
      compromises the fluent production of words and the correct use and comprehension
      of grammar. FOXP2 patients have structural and functional abnormalities in the
      striatum of the basal ganglia, which also express high levels of FOXP2. Since
      human speech and learned vocalizations in songbirds bear behavioral and neural
      parallels, songbirds provide a genuine model for investigating the basic
      principles of speech and its pathologies. In zebra finch Area X, a basal ganglia
      structure necessary for song learning, FoxP2 expression increases during the time
      when song learning occurs. Here, we used lentivirus-mediated RNA interference
      (RNAi) to reduce FoxP2 levels in Area X during song development. Knockdown of
      FoxP2 resulted in an incomplete and inaccurate imitation of tutor song.
      Inaccurate vocal imitation was already evident early during song ontogeny and
      persisted into adulthood. The acoustic structure and the duration of adult song
      syllables were abnormally variable, similar to word production in children with
      DVD. Our findings provide the first example of a functional gene analysis in
      songbirds and suggest that normal auditory-guided vocal motor learning requires
      FoxP2.

PMID- 18052610
TI  - The signal sequence coding region promotes nuclear export of mRNA.
AB  - In eukaryotic cells, most mRNAs are exported from the nucleus by the
      transcription export (TREX) complex, which is loaded onto mRNAs after their
      splicing and capping. We have studied in mammalian cells the nuclear export of
      mRNAs that code for secretory proteins, which are targeted to the endoplasmic
      reticulum membrane by hydrophobic signal sequences. The mRNAs were injected into
      the nucleus or synthesized from injected or transfected DNA, and their export was
      followed by fluorescent in situ hybridization. We made the surprising observation
      that the signal sequence coding region (SSCR) can serve as a nuclear export
      signal of an mRNA that lacks an intron or functional cap. Even the export of an
      intron-containing natural mRNA was enhanced by its SSCR. Like conventional
      export, the SSCR-dependent pathway required the factor TAP, but depletion of the
      TREX components had only moderate effects. The SSCR export signal appears to be
      characterized in vertebrates by a low content of adenines, as demonstrated by
      genome-wide sequence analysis and by the inhibitory effect of silent adenine
      mutations in SSCRs. The discovery of an SSCR-mediated pathway explains the
      previously noted amino acid bias in signal sequences and suggests a link between
      nuclear export and membrane targeting of mRNAs.

PMID- 18052612
TI  - [How long is the anti-retroviral therapy?].

PMID- 18052611
TI  - The inhibition of polo kinase by matrimony maintains G2 arrest in the meiotic
      cell cycle.
AB  - Many meiotic systems in female animals include a lengthy arrest in G2 that
      separates the end of pachytene from nuclear envelope breakdown (NEB). However,
      the mechanisms by which a meiotic cell can arrest for long periods of time
      (decades in human females) have remained a mystery. The Drosophila Matrimony
      (Mtrm) protein is expressed from the end of pachytene until the completion of
      meiosis I. Loss-of-function mtrm mutants result in precocious NEB.
      Coimmunoprecipitation experiments reveal that Mtrm physically interacts with Polo
      kinase (Polo) in vivo, and multidimensional protein identification technology
      mass spectrometry analysis reveals that Mtrm binds to Polo with an approximate
      stoichiometry of 1:1. Mutation of a Polo-Box Domain (PBD) binding site in Mtrm
      ablates the function of Mtrm and the physical interaction of Mtrm with Polo. The
      meiotic defects observed in mtrm/+ heterozygotes are fully suppressed by reducing
      the dose of polo+, demonstrating that Mtrm acts as an inhibitor of Polo. Mtrm
      acts as a negative regulator of Polo during the later stages of G2 arrest.
      Indeed, both the repression of Polo expression until stage 11 and the
      inactivation of newly synthesized Polo by Mtrm until stage 13 play critical roles
      in maintaining and properly terminating G2 arrest. Our data suggest a model in
      which the eventual activation of Cdc25 by an excess of Polo at stage 13 triggers
      NEB and entry into prometaphase.

PMID- 18052613
TI  - [Analysis of the causes and predictive factors for discontinuing treatment with
      tenofovir in pretreated HIV patients].
AB  - OBJECTIVE: To determine the frequency and causes for discontinuing treatment with
      tenofovir and analyse possible predictive factors for changing this therapy in
      pretreated HIV patients. METHOD: A multi-centre, observational and retrospective
      study of all HIV patients undergoing treatment with tenofovir between July 2002
      and December 2005. Data were obtained from databases for outpatients attending
      the three pharmacy departments participating in the study, and by reviewing
      clinical histories. The main sociodemographic, clinical and analytical variables
      at the start of treatment with tenofovir were collected. The causes for
      discontinuing treatment were classified as follows: adverse effects, virological
      failure, death and "other causes". A survival analysis was performed using the
      Kaplan-Meier method to analyse the possible predictive factors for discontinuing
      treatment. RESULTS: A total of 733 patients were included in the study and the
      median treatment period was 34.7 months. A total of 23.8% of patients
      discontinued treatment for the following reasons: adverse effects (43.2%), death
      (17.7%), virological failure (14.8%) and "other causes" (24.4%). There were 99
      cases of lost to follow-up. In the survival analysis an association was found
      between normal serum creatinine values (p = 0.0042) at the start of treatment and
      the statistically significant probability of discontinuing treatment.
      CONCLUSIONS: Almost a quarter of the patients discontinued treatment with
      tenofovir during the study. The main cause for this was adverse effects. No
      association was found between any abnormal basal analytical parameter and a
      greater probability of discontinuing treatment.

PMID- 18052614
TI  - [Interruption to treatment with combined lopinavir/ritonavir therapy in HIV
      positive patients].
AB  - OBJECTIVE: To describe the extent of interruptions to treatment with therapies
      which include the combination of lopinavir-ritonavir within the SNS (Spanish
      National Health System), as well as identify the causes of these interruptions
      and analyse the factors associated with the same. METHOD: Retrospective cohort of
      197 seropositive patients, who began treatment with lopinavir-ritonavir between
      January 2000 and October 2002. The patients attended the outpatient
      pharmaceutical care unit and were followed-up until December 2002. Interruptions
      and their causes were identified and the factors associated with the interruption
      were analysed using proportional hazard models. RESULTS: The mean follow-up
      period was 263 days and 38.6% of patients interrupted therapy. The most common
      causes of interruption were intolerance (30.3%), non-compliance (21.1%) and
      therapy failure (5.26%). The mean treatment period was 487 days (95% CI: 432 to
      542) and 50% of patients who interrupted treatment did so within the first 4
      months. No associations were found between patient or treatment characteristics
      and the risk of interruption. CONCLUSIONS: The percentage of interruptions was
      lower than those in other observational studies, but greater than those in
      clinical trials. The significance of the causes of interruption was similar and
      no factor associated with the risk of interruption was found.

PMID- 18052615
TI  - [Implementation of the guidelines for the introduction of new drugs (GINF) in
      Andalusian hospitals].
AB  - OBJECTIVE: To measure the level of implementation of the GINF (guidelines for the
      introduction of new drugs) in Andalusian hospitals, describe the characteristics
      of this implementation and analyse if any of the hospital s dependent variables
      could influence these characteristics. METHOD: A telephone survey was carried out
      in the hospitals included in the Department of Health list. The survey consisted
      of 11 closed questions on different variables in the hospital and the GINF use
      profile, and an open question about the improvements carried out and proposals
      for improvement. The results were analysed according to the type of hospital
      (category, training, geographical location) in order to detect possible
      differences. RESULTS: A target population of 31 hospitals was identified. The
      survey was carried out in 29 of these; the level of implementation was 96.5% in
      the responding hospitals. 23 hospitals used the GINF for 100% of drugs, 6 had
      carried out local modifications and 80% made proposals for improvement.
      Significant differences were found in the implementation of the GINF according to
      resident/intern pharmacist training (p = 0.049), the geographical location (p =
      0.004) and the hospital category (p < 0.001). CONCLUSIONS: The GINF have been
      implemented in almost all public Andalusian hospitals as the guidelines for
      requesting new drugs. Very few local modifications have been carried out to the
      guidelines, although numerous proposals for improvement have been made.
      Differences in use have been identified (No. of drugs, different versions)
      according to the hospital characteristics (location, training and complexity
      classification). They are considered a useful tool and influence the drug
      selection process, in particular in training hospitals with a higher
      classification.

PMID- 18052616
TI  - [Retrospective analysis of the carboplatin dosage and relationship with toxicity
      in cancer patients].
AB  - OBJECTIVE: To analyse carboplatin dosage in cancer patients in order to establish
      whether they are over- or underdosed in comparison to the theoretical dose
      calculations during the first cycle of chemotherapy and to find a relationship
      between the dosage in the first cycle and dose reduction in subsequent cycles, as
      a result of adverse effects related to the same. METHOD: Retrospective analysis
      over a one year period of prescriptions of chemotherapy with carboplatin.
      Patients were stratified into 4 groups according to body mass index and serum
      creatinine values. The mean percent error (MPE) was used to determine the
      relationship between the dose received and the theoretical dose calculation
      during the first cycle. The Mann-Whitney U test was used to study the possible
      relationship between patients dosage during the first cycle and dose reduction in
      subsequent cycles. RESULTS: A total of 86 patients were selected. Only the cohort
      of patients who were overweight/obese showed significant differences between the
      theoretical dose calculation and the dose actually received. The mean MPE value
      with the standard error for this group was 7.963 +- 2.610%. No links were found
      with the dose reduction in subsequent cycles for this cohort of patients.
      CONCLUSIONS: Not using adjusted weight or serum creatinine values in the
      Cockcroft-Gault equation may lead to incorrect doses of carboplatin in obese
      patients. Studies including a larger number of patients are required to confirm
      the relationship between overdosing during the first cycle and dose reduction in
      subsequent cycles, as a result of carboplatin toxicity.

PMID- 18052617
TI  - [Prescription errors after the implementation of an electronic prescribing
      system].
AB  - OBJECTIVE: This study sets out to identify, compare and evaluate the medication
      errors of a manual prescribing system and an electronic prescribing system during
      the prescription and transcription phases. METHOD: A prospective study of two
      clinical in-patient units (pneumology and infectious diseases) in one general
      hospital. Two phases were studied; before and after an electronic prescribing
      system was implemented. Each phase lasted one month. A comparative analysis was
      carried out of the medication errors in the medical prescription process, the
      transcription process and the administration recording process carried out by
      nursing staff as well as the pharmacist s transcriptions/validations. RESULTS: A
      total of 3,908 patient treatment errors and 129 patient identification errors
      were detected during both of the periods studied. The rate of errors in patient
      identification or treatment orders using the manual prescribing system was 14.4
      against 1.3% after the electronic system was implemented. The relative risk
      reduction for infectious diseases and pneumology was 100 and 85.44%, respectively
      (statistically significant). In general, relative risk reduction was achieved in
      both units, oscillating between 78.91 and 100%. The absolute risk reduction
      oscillated between 5.09 and 30.45% for errors in drug data, doses, frequency/time
      and route of administration. These results were statistically significant.
      CONCLUSIONS: The electronic prescribing system has reduced errors in the
      identification, prescription and transcription of pharmacological treatment and
      has consequently helped to improve the quality and safety of drug treatment
      received by patients.

PMID- 18052618
TI  - [Quality assessment of two pharmaceutical care models for onco-haematological
      patients].
AB  - OBJECTIVE: To compare the quality of two pharmaceutical care models (with and
      without pharmacist participation in the clinical team), in hospitalised onco
      haematological patients. METHOD: A prospective cohort study in the oncology and
      haematology departments of a university hospital over a 26-month period. A
      centralised model (model C) was used over 16 months and a decentralised
      integration model (model D) was used during the remaining 10 months. The Iaser
      (c) methodology was used to identify candidates for improved drug treatment and
      for the follow up of patients with drug-related problems (DRP). The results
      obtained were compared using a series of pharmaceutical care quality indicators.
      RESULTS: The rate of patients identified with DRP increased significantly (RR =
      2.3; CI 95%: 1.8-2.8), as did the frequency of DRP (RR = 3.4; CI 95%: 2.8-4.0),
      in particular the frequency of preventable DRP (RR = 3.8; CI 95%: 2.5-4.2). The
      identification of the type of DRP relating to indication significantly increased
      (RR = 4.5; CI 95%: 3.4-5.8), followed by DRP relating to efficacy and safety. The
      acceptance of pharmaceutical care interventions did not improve proportionally
      (RR = 1.0; CI 95%: 0.9-1.1), although there was a significant increase in
      practices with clinical importance (RR = 4.1; CI 95%: 3.3-5.0), that showed an
      objective or subjective decrease in the risk of drug-related morbidity in
      patients (RR = 4.1; CI 95%: 3.1-5.4). CONCLUSIONS: Pharmacist participation in
      the interprofessional team improved the quality of pharmaceutical care, in
      particular with respect to the increased identification of possibilities to
      improve drug treatment and clinically significant pharmaceutical practices. As a
      result, the risk of drug-related morbidity can be reduced in patients.

PMID- 18052620
TI  - Validation of high-performance liquid chromatography methods for determination of
      zidovudine, stavudine, lamivudine and indinavir in human plasma.
AB  - OBJECTIVE: Simple methods for the determination of zidovudine (AZT), stavudine
      (d4T), lamivudine (3TC) and indinavir (INV) in human plasma by reversed-phase
      liquid chromatography (HPLC) with UV detection were described and validated.
      METHOD: Solid-liquid extraction procedures were applied to the samples prior to
      analysis. Chromatography was performed on a C-18 analytical columns and the
      retention time ranged from 6.8 to 8.0 min for stavudine, 7.5 to 9.0 min for
      lamivudine, 11.2 to 11.9 min for zidovudine and indinavir. Four methods were
      validated for specificity, inter-and intra-assay precision and accuracy, absolute
      recovery and stability. RESULTS: Analytical curve ranged from 10-1600 ng/ml for
      stavudine, 50-3200 ng/ml for lamivudine, 0.05-5.0 microg/ml for zidovudine and
      0.1-10.0 microg/ml for indinavir. Analytes stability during sampling processing
      and storage were established. Extraction recoveries are higher than 89% for all
      formulations. CONCLUSIONS: These methods proved to be simple, accurate and
      precise, and are currently in use in our laboratory for the quantitative analysis
      of antiretrovirals products in plasma, and for further pharmacokinetics and
      bioequivalence studies.

PMID- 18052619
TI  - [Patients at risk of malnutrition: assessment of 11 cases of severe malnutrition
      with individualised total parenteral nutrition].
AB  - OBJECTIVE: To describe and assess the efficacy and safety of individualised
      nutritional support during the first week of total parenteral nutrition in
      moderately to severely malnourished patients who are susceptible to the refeeding
      syndrome. METHOD: Retrospective observational study carried out between January
      2003 and June 2006, including adult patients with moderate to severe malnutrition
      who received = 5 days total parenteral nutrition. The nutritional support was
      described and the appearance of severe hydroelectrolytic and metabolic
      disturbances were assessed during the first week of nutrition. RESULTS: The study
      included 11 patients with a mean body mass index of 15.4 kg/m2. These patients
      received an average of 23 Kcal/kg/day. They did not show any signs of severe
      hydroelectrolytic or metabolic disturbances. Three patients presented with
      hypophosphataemia, five with hypokalaemia and four with hypomagnesaemia, all of
      which were mild to moderate and with the exception of two cases, all were
      corrected within one week of feeding. CONCLUSIONS: Individualised nutritional
      support in moderately to severely malnourished patients does not produce
      refeeding syndrome. Individualised nutrition is an essential strategy for
      avoiding complications associated with overfeeding.

PMID- 18052621
TI  - [Observational study of the efficacy and tolerability of bosentan for the
      treatment of pulmonary hypertension in a tertiary referral hospital].
AB  - OBJECTIVE: The pathogenesis of pulmonary hypertension (PHT) involves elevated
      levels of endothelin. Bosentan is a receptor antagonist used for the treatment of
      this disease. The purpose of the study is to assess the efficacy and tolerability
      of this drug in clinical practice. METHOD: A retrospective observational study of
      10 patients with primary pulmonary hypertension (seven) and secondary to
      pulmonary thromboembolism (PTE), treated with bosentan. The decrease in systolic
      pulmonary artery pressure (SPAP) and the New York Heart Association (NYHA)
      functional classification were measured, together with treatment safety based on
      transaminase levels in the mid term and long term until the treatment period of
      two years was completed. RESULTS: The decrease in SPAP between the beginning and
      the end of the treatment was not significant. Three of the ten patients began
      treatment in class II, five in class III and two in class IV. After 12 months of
      treatment, six patients were in class II, two in class IV, one patient died and
      another stopped the treatment due to toxicity. Four patients continued the
      treatment for 24 months, and the results were compared with those obtained during
      the first year: Two patients remained in class II, one patient deteriorated to
      class III and the four died. CONCLUSIONS: Bosentan is shown to be effective after
      six months of treatment, losing efficacy after two years. Bosentan gave
      satisfactory results in PHT secondary to PTE.

PMID- 18052622
TI  - [Severe levofloxacin-induced thrombocytopenia].

PMID- 18052623
TI  - [Treatment of Lambert-Eaton syndrome with 3,4- diaminopyridine and
      pyridostigmine].

PMID- 18052624
TI  - [Bevacizumab-induced serious heart failure in a patient treated with
      anthracyclines].

PMID- 18052625
TI  - [Diagnosis of Nerium oleander poisoning: is a single analytical method enough?].

PMID- 18052627
TI  - [Advances in cervical cancer prevention: HPV vaccines].

PMID- 18052628
TI  - [Treatment with cetuximab in metastatic colorectal cancer patients who do not
      express the epidermal growth factor receptor].
AB  - OBJECTIVE: To evaluate the response to cetuximab, in terms of time passed until
      disease progression and overall survival, in patients with colorectal cancer
      (CRC) in which the epidermal growth factor receptor (EGFR) is undetectable.
      METHOD: Nine EGFR-negative patients (confirmed by an immunohistochemistry study),
      who were being treated with cetuximab, were selected. Variables collected:
      demographic data, diagnosis, previous treatments, time since first metastasis to
      start of treatment with cetuximab, adverse events and tumour markers. The
      response was monitored using tumour markers and disease progression. Well-being
      was assessed using the Karnofsky performance status (KPS) or that of the Eastern
      Cooperative Oncology Group (ECOG). RESULTS: 22% men (2/9) with a median age of 48
      (31-63). The median time from being diagnosed with the metastatic disease to the
      start of treatment with cetuximab was 19 months (12-48). All patients had failed
      an irinotecan-based regime, 77.77% (7/9) had also failed one which included
      oxaliplatin. The median number of cycles with cetuximab was 14 (6-32). The main
      adverse event was the appearance of an acneiform rash in 100% of the cases. The
      median time until disease progression was 7 months (3-16) and 10.2 months (4-24)
      for overall survival. The results for well-being showed a KPS of between 80-100%
      and an ECOG of < 2. The results obtained in the present study for overall
      survival and time until disease progression are higher than those in the pivotal
      study (10.2 compared to 8.6 months and 7 compared to 4.1 months respectively).
      CONCLUSIONS: According to the results obtained, the use of assessing the EGFR
      expression (by the immunohistochemistry technique at least), as a means of
      predicting response to treatment with cetuximab may be questioned. This suggests
      that selecting patients using the routine assessment of this receptor is
      inappropriate, since it excludes patients who may potentially benefit from the
      treatment. However, more clinical trials are required in this area in order to
      confirm these conclusions.

PMID- 18052629
TI  - [Dose intensity received in breast cancer treatment with chemotherapy].
AB  - OBJECTIVE: To know relative dose intensity (RDI) in patients with breast cancer
      treated with chemotherapy. To determine the number of patients where RDI was <
      85% of that programmed and the possible cause. METHOD: Retrospective study, four
      month selection period. The following were recorded: age, body surface, protocol
      applied, intention of treatment, frequency of administration of cycles, number of
      cytostatic treatments previously received and filgrastim administration. The
      average RDI per patient and protocol was calculated. RESULTS: 110 patients were
      analysed, the average age of them being 55.4 years (interval: 31-84), average
      body surface 1.7 m2 (1.3-2.4). Overall average RDI was 91.0% (SD 10.7). 93.8%
      (10.6), 95.8% (6.3) and 81.9% (18.5) in neoadjuvant, adjuvant and palliative
      treatments, respectively. 20% of the patients did not reach a RDI = 85% of that
      programmed, average RDI 69.5% (3.29). A delay in the administration of
      chemotherapy equal or greater than seven days occurred in 45.4% of the cases,
      average RDI 80.7% (16.0). In the episodes where the dose was reduced because of
      toxicity, the RDI was 75.6% (13.6). Significant inverse ratios were obtained with
      age (p = 0.02) and line of treatment (p = 0.03) with the RDI. In 36.8%, dose
      reduction was caused by neutropenia; 52.9% received filgrastim. CONCLUSIONS: Most
      patients received the appropriate RDI. Age, previous treatments and intention of
      treatment were the variables with the greatest impact on the dose received. The
      delay in administering the cycle was the most frequent act minimising the
      toxicity and which least affected the treatment.

PMID- 18052630
TI  - [Alerts system associated with computerized physician order entry: analysis and
      identification of improvement points].
AB  - OBJECTIVE: To make a quantitative analysis of the alerts associated with a
      computerized physician order entry system and identify opportunities to improve
      the system. METHOD: A retrospective observational study in a general hospital
      with 750 beds, 500 of which have a computerized physician order entry system
      installed. The frequency per type and medication of 525,691 alerts produced for a
      year in the prescription of drug treatments to 15,466 patients was analysed,
      entering these on a database. The system includes three categories of alert
      relating to the drug, the characteristics of the patient and the hospital
      medicine policy. By means of a failure mode and effects analysis, opportunities
      for improving the system were identified and corrective measures were suggested.
      RESULTS: It has been observed that from the total of 1,084 drugs, 20 of them
      produce 34% of alerts. The ten most frequently active ingredients involved are:
      potassium chloride, acenocumarol, imipenem, lorazepam, diazepam, mycophenolate,
      enoxaparin, tacrolimus, calcium carbonate and cyclosporine. The most frequent
      alerts generated during electronic prescription are associated with duplicated
      therapy (35.4%), renal failure (27.6%) and risk due to advanced age (17.2%), with
      these groups accounting for 80.2% of the total. The excess of alerts and
      information provided by the alerts were identified as priority improvement
      points. CONCLUSIONS: The system produced excessive alerts which led to the risk
      of them being ignored and reducing the capacity to prevent adverse drug events.
      Modifications are required for the design of the alert system, which also needs
      to be continuously updated.

PMID- 18052631
TI  - [Approach to evaluating the clinical relevance of drug interactions in HIV
      infected patients].
AB  - OBJECTIVE: To systematize information about drug interactions in HIV/AIDS, and to
      test a proposal to identify and evaluate drug interactions considered clinically
      relevant highlight those associated to pharmacokinetic mechanism. METHOD: We
      performed a MEDLINE search of the literature published in English and Spanish
      from January 1995 to June 2007 on antiretroviral drug interactions in humans.
      Search terms were drug interactions and antiretroviral agents (or drugs) in
      title/abstract field. So, we searched for clinically relevant drug interactions
      of specific drugs commonly administered to patients with HIV, and we reviewed
      references cited in relevant articles. Finally, we followed a proposal to
      evaluate and use the clinical relevance complemented with a classification based
      on severity and probability of its occurrence. RESULTS: A total of 378 articles
      were achieved, among then we acquire the full text of 296. We presented the type
      and mechanism of drug interactions in HIV-infected patients. We evaluate and use
      the clinical relevance of drug interactions. Among pharmacokinetic interactions
      considered clinically relevant, approximately to 80% was related to changes in
      systemic clearance [due to induction or inhibition of systemic metabolic activity
      of cytochrome P450 3A4 (CYP3A4)]; and 15% with changes in bioavailability [(due
      to changes in gastrointestinal pH, presystemic metabolism or activity of the
      glicoprotein -P (Gp-P)]. CONCLUSIONS: Among patients with HIV/AIDS, most of the
      pharmacokinetic interactions of clinical relevance are attributed to inhibition
      or induction of hepatic systemic metabolic activity, mainly of CYP3A4.

PMID- 18052632
TI  - [Lipase and total amylase and its isoenzymes as markers of pancreatic injury in
      patients treated with antiepileptic drugs].
AB  - OBJECTIVE: The study of the serum lipase and total amylase and its isoenzymes as
      biochemical markers of pancreatic injury in patients treated with valproic acid
      and other enzyme-inducing antiepileptic drugs. METHOD: The serum activities of
      lipase and total amylase and its isoenzymes were determined in 41 patients
      treated in monotherapy with valproic acid, 50 patients in mono/polytherapy with
      phenytoin, phenobarbital and carbamazepine, and 30 healthy controls. RESULTS: In
      the first group of patients a clinically significant difference in relation to
      the control group was not obtained for any of the enzyme activities studied;
      however, in the group of patients treated with enzyme-inducing antiepileptic
      drugs clinically significant differences were obtained for lipase and pancreatic
      amylase. In this group of patients, the activity of pancreatic amylase was
      clearly increased in two cases (4%), suggesting the existence of a pancreatic
      damage. In the patients studied, the total amylase showed a poor specificity as a
      biochemical marker for pancreatic injury, and the greater serum activity observed
      in one case corresponds to an increase of the salivar isoenzyme. The sensitivity
      of the lipase is smaller than amylase pancreatic isoenzyme. CONCLUSIONS: In
      patients treated with antiepileptic drugs, the determination of the pancreatic
      isoenzyme of amylase would be of interest even in absence of clinical signs for
      acute pancreatitis.

PMID- 18052633
TI  - [A time series analysis of the cost of the most common drug treatment groups in
      an intensive care unit].
AB  - OBJECTIVE: To determine the evolution of the most common drug treatment groups in
      an intensive care unit over a period of seven years, characterise the time-cost
      relationship and establish an ARIMA prediction model using Box-Jenkins
      methodology. METHOD: A retrospective analysis of the costs of thirteen drug
      treatment groups was carried out in an intensive care unit with 19 beds between
      the period of 1998 to 2004. The monthly cost of these treatment groups
      constituted the time series. The descriptive analysis was carried out by means of
      descriptive statistics and graphs. The trend was analysed by means of smoothing
      by weighted local regression, and seasonality was analysed by multiple linear
      regression. Stochastic models for time series were developed using Box-Jenkins
      methodology for descriptive and forecasting purposes. RESULTS: 70% of drug costs
      are generated by thirteen groups. Three of these groups display a downward trend,
      four have an upward trend and the remaining groups do not display any significant
      trend. Seasonality is only relevant in series with upward trends. The ARIMA model
      allows models to be obtained for seven series. CONCLUSIONS: The descriptive cost
      analysis, the determination of trends and the analysis of seasonality provide
      information about the dynamics in drug use in an intensive care unit. However,
      the use of ARIMA models to optimise the planning of treatment resources in these
      types of hospital units is still extremely limited.

PMID- 18052634
TI  - [Osmolality of oral liquid dosage forms to be administered to newborns in a
      hospital].
AB  - OBJECTIVE: Oral administration of hypertonic solutions can contribute to
      intestinal damage in the initial stages of neonatal necrotizing enterocolitis.
      The purpose of this study is to determine the osmolality of oral liquid dosage
      forms used in a division of neonatology and to establish some recommendations for
      their dilution. METHOD: The osmolality of 26 oral liquid dosage forms has been
      measured using the freezing-point depression method. RESULTS: Oral liquid dosage
      forms used in the division of neonatology present an osmolality greater than 350
      mOsm/kg H2O. 19.2% of all the analysed forms presented an osmolality lower than
      1500 mOsm/kg H2O, 80.7% were over that figure, while 23% presented an extremely
      high osmolality (> 5,000 mOsm/kg H2O). CONCLUSIONS: Knowledge of osmolality of
      oral liquid dosage forms in the division of neonatology enables the risk of
      intestinal aggression caused by enteral administration of the medication to be
      assessed.

PMID- 18052635
TI  - [Acute digitalic intoxications in aged patients and proposal of a digitalization
      nomogram].

PMID- 18052636
TI  - [Zoledronic acid free adjustment according to renal function: results of
      pharmacists interventions].

PMID- 18052637
TI  - [Ishikawa diagram and barrier analysis implemented to a medication error that
      induces rhabdomyolysis].

PMID- 18052638
TI  - [Treatment with activated factor VII after acute bleeding due to aortic
      dissection].

PMID- 18052639
TI  - [Hallucinations by administration of a standard regimen of clarithromycin].

PMID- 18052640
TI  - [Delivering medications via pneumatic tube system].

PMID- 18052641
TI  - [Bile secretion -- at the crossroads of colorectal carcinogenesis].

PMID- 18052642
TI  - [Effect of ursodeoxycholic acid in an experimental colon cancer model].
AB  - AIMS: The present study was designed to examine the effect of ursodeoxycholic
      acid as chemoprotective agent in experimental colon carcinogenesis in rats.
      MATERIAL AND METHODS: One hundred and ten 10-week-old, Sprague-Dawley rats were
      divided into five groups: group A (20), no treatment. Group B (20), receiving
      daily both ursodeoxycholic acid (UDCA) 4 mg/kg of body weight and ethanol 1.23
      g/kg of body weight added to the drinking water from the beginning of the study
      through 24 weeks. Group C (30), receiving 18 weekly doses of dimethylhydrazine
      (DMH) 21 mg/kg of body weight subcutaneously from the beginning of the study,
      with the same doses of UDCA and ethanol as in group B. Group D (20), ethylen
      diamin-tetracetic acid solution alone for 18 weeks. Group E (20), receiving the
      same doses of ethanol plus DMH injections as in group C. All experimental animals
      were sacrificed after 25-27 weeks. RESULTS: No tumors developed in
      dimethylhydrazine-free groups. No significant differences in number of tumor-free
      animals, number of tumors per rat, and macro-microscopic tumor findings were seen
      between animals in group C and animals in group E. CONCLUSIONS: We concluded that
      such an ursodeoxycholic acid supplementation did not modify colorectal
      carcinogenesis using a dynamic DMH-induced model in rats.

PMID- 18052643
TI  - [Prevalence of Helicobacter pylori infection in the healthy population of Madrid
      (Spain)].
AB  - OBJECTIVE: To determine the prevalence of Helicobacter pylori infection in the
      healthy population of Madrid Autonomous Community (AC). MATERIAL AND METHODS: A
      descriptive, cross-sectional study where Helicobacter pylori infection is
      diagnosed by means of the 13C-urea breath test. RESULTS: A total of 618 subjects
      were studied. Among these, 481 were considered evaluable with a prevalence of
      Helicobacter pylori infection of 60.3%. In this cohort 36.4% were men and 63.6%
      were women, with a prevalence of 60.6 and 60.1%, respectively, and no relevant
      differences between both subgroups. The median age of patients was 37.5 years
      (range 4-82), and a statistically significant linear relationship between
      Helicobacter pylori infection and age (linear chi2 =33.31; p < 0.001) was
      established -chances of infection increase with age. Prevalence increases with
      age and peaks at 60 to 69 years (83.3% infected). For 169 subjects (35.1%)
      education level was unknown, and no relationship between this level and
      Helicobacter pylori infection was found. CONCLUSIONS: The study shows that the
      prevalence of Helicobacter pylori infection in the healthy population of Madrid
      AC is high (60.3%), progressively increases with age, and peaks in people in
      their sixties. The sample showed no differences regarding sex or education level.

PMID- 18052644
TI  - Spiegelian hernia: mesh or not?
AB  - OBJECTIVE: The purpose of this study was to report our experience in management
      and clinical result of Spigelian hernia with preperitoneal mesh repair or without
      mesh repair. EXPERIMENTAL DESIGN: Retrospecitve analysis. SUBJECTS: the medical
      records of 11 cases of Spigelian hernia with surgical treatment were reviewed.
      The clinical characteristic, treatment and clinical result were evaluated.
      RESULTS: of the 11 cases that were evaluated, 7 patients underwent open repair of
      hernia without extra-peritoneal mesh (group A), the other 4 patients underwent
      open surgery with extra-peritoneal mesh (group B). There were no significant
      difference in age, gender, body mass index, underlying diseases, symptoms,
      duration of symptoms, features of hernia sac and method of approach. No
      recurrence was found in these two groups. The mean follow-up time was 8.5 +/- 3.2
      (years) in group A and 6.7 +/- 2.1 (years) in group B. CONCLUSIONS: whether open
      repair of spigelian hernia with or without extra-peritoneal mesh gives the same
      and well result.

PMID- 18052645
TI  - [Clinical aspects and endoscopic management of gastrointestinal bleeding from
      Dieulafoy's lesion].
AB  - OBJECTIVE: the aim of the study was to assess the incidence, clinical
      presentation, location, and response to endoscopic therapy of gastrointestinal
      bleeding from Dieulafoy's lesion. MATERIAL AND METHOD: ALL consecutive episodes
      of gastrointestinal bleeding due to Dieulafoy's lesion seen between 2000 and 2006
      were retrospectively reviewed. All main clinical and endoscopic data were
      collected: type and effectiveness of endoscopic therapy, rebleeding,
      complications, and mortality during hospitalization. RESULTS: WE found 41
      patients, 26 males and 15 females, median age of 71.19 years. Dieulafoy's lesion
      accounted for 1.55% of all gastrointestinal bleeding episodes during the study
      period. The incidence of Dieulafoy's lesion was 2.2 cases/100.000
      inhabitants/year. Active bleeding at endoscopy was present in 85.36%, and
      comorbidity in 92.68%. The stomach was the most frequent location (60.97%),
      followed by duodenum (29.26%). Endoscopic therapy achieved initial hemostasis in
      all cases. Three patients (7.31%) initially treated with epinephrine injection
      showed rebleeding and properly responded to a second session of endoscopic
      therapy. No surgery was needed. The mortality rate during hospitalization was
      4.87%. CONCLUSIONS: Dieulafoy's lesion is an uncommon, but potentially severe
      cause of gastrointestinal bleeding. It may be found in any location within the
      gastrointestinal tract. Endoscopic therapy is effective and safe. Injected
      epinephrine alone is associated with a higher risk of rebleeding.

PMID- 18052646
TI  - [Spanish translation, adaptation, and validation of the 32-item questionnaire on
      quality of life for inflammatory bowel disease(IBDQ-32)].
AB  - INTRODUCTION: The measurement of health-related quality of life (HRQoL) has an
      established relevance in the assessment, management, and follow-up of
      inflammatory bowel disease. The most commonly used measuring instrument is the 32
      item version of Inflammatory Bowel Disease Questionnaire (IBDQ-32), which has
      never been adapted to Spanish. OBJECTIVE: To translate IBDQ-32 into Spanish, and
      to establish its validity, reliability, and sensitivity both in ulcerative
      colitis and Crohn s disease. METHOD: A prospective study in two phases 
      translation into Spanish and subsequent validation of IBDQ-32. Translation was
      based on the validated Spanish version of IBDQ-36, and IBDQ-32 items not included
      in IBDQ-36 were translated from scratch. Once the IBDQ32 translation was
      completed a comprehension-specific questionnaire was administered. To establish
      IBDQ-32 psychometric properties a group of patients completed both the validated
      Spanish version of IBDQ-36 and IBDQ-32. RESULTS: Eighty-four patients (53 with
      Crohn s disease and 31 with ulcerative colitis) were included. Median overall
      scores in both questionnaires for all 84 patients did not differ (6.1 vs. 6.2, p
      = ns), and Spearman s correlation was highly significant (r = 0.97, p < 0.001).
      The ability to discriminate between patients in flare-up or remission was also
      equivalent for both questionnaires (6.4 vs. 6.4 with r = 0.96 in remission and
      3.8 vs. 3.9 with r = 0.95 active, p < 0.001 for remission vs. activity). These
      results were obtained in both the analyses for CD and UC independently (6.4 vs.
      6.4 and 6.7 vs. 6.6, respectively; p = ns). CONCLUSION: The Spanish version of
      IBDQ-32 is valid and discriminating for patients with Crohn s disease or
      ulcerative colitis.

PMID- 18052648
TI  - [Hepatobiliary manifestations in inflammatory bowel disease].

PMID- 18052647
TI  - [Ultrasound-guided biopsy of the pancreas: a multicenter study].
AB  - OBJECTIVE: Members of "Asociacion de Ecografia Digestiva" decided to carry out a
      multicenter retrospective study on fine-needle aspiration biopsy for pancreatic
      space-occupying lesions under ultrasonographic guidance and via the percutaneous
      route in order to assess this technique s performance versus endoscopic
      ultrasound-guided biopsy. SUBJECTS: 10 hospitals for a total of 222 patients with
      suspiciously malignant, 8-120-mm pancreatic lesions were included in the study.
      RESULTS: The analysis of results shows a sensitivity of 89%, a specificity of
      98%, a positive predictive value of 99%, and a negative predictive value of 74%,
      for an overall diagnostic accuracy of 91%. No major complications occurred.
      CONCLUSION: Percutaneous fine-needle aspiration for pancreatic lesions is highly
      cost-effective and has few and mild complications.

PMID- 18052649
TI  - Intrahepatic arteriovenous fistula resulting from needle biopsy.

PMID- 18052650
TI  - [Gastric polyposis in FAP].

PMID- 18052651
TI  - Retrorectal tumors: excision by transanal endoscopic microsurgery.
AB  - Tumours within the retrorectal space are uncommon. Due to their rarity and
      diverse symptoms they are often misdiagnosed or mistreated. We report three cases
      of women presenting a variety of symptoms including increased rectal pain,
      recurrent abscesses/fistulas and constipation. Upon clinical examination and
      further investigations using MR scan, endorectal ultrasound and endoscopy, a
      retrorectal mass was suspected in all three cases. In order to achieve a complete
      excision of the tumor while minimizing trauma, transanal endoscopic microsurgery
      (TEM) was performed. The histology of the multicystic tumor revealed in all three
      cases a tailgut cyst. As far as we know this is the first report describing the
      use of TEM for surgical treatment of tumors located in the retrorectal space.

PMID- 18052652
TI  - [Upper esophageal hemangioma successfully treated by laser].

PMID- 18052653
TI  - [Jaundice caused by afferent loop volvulus following Billroth-II gastrectomy].

PMID- 18052654
TI  - [Bilioenteric fistula from a penetrating duodenal ulcer].

PMID- 18052655
TI  - [Large esophagic ulcer following doxycycline treatment].

PMID- 18052656
TI  - [Obstructive jaundice secondary to pancreatic metastases of a soft-tissue
      sarcoma].

PMID- 18052657
TI  - [Intestinal malrotation in adults and acute appendicitis].

PMID- 18052658
TI  - [The significance of CARD15 mutations in Crohn's disease. The Spanish
      contribution].

PMID- 18052659
TI  - [CARD15 mutations are poorly related to Crohn's disease phenotypes in Asturias].
AB  - BACKGROUND: the association between the three common CARD15 gene mutations
      (R702W, G908R, L1007fs) and the genetic susceptibility to Crohn s disease (CD)
      have been confirmed by several studies, with some differences found, in relation
      to geographic areas and ethnic groups. OBJECTIVES: To analyze the prevalence of
      CARD15 gen and its polymorphisms in patients with CD in Asturias and its possible
      correlation with the different genotypes of the disease. METHODS: a total of 216
      CD patients recruited from Asturias (North of Spain) and 86 ethnically matched
      healthy controls, were typed using Hybprobes on a LightCycler instrument for
      CARD15 mutations. Patients were subdivided according to Vienna classification. We
      have studied the frequency of these mutations in the different subgroups of CD
      patients and analyzed its contribution to the disease clinical characteristics
      and progression. RESULTS: carrier frequencies for CARD15 mutations in our CD
      patients were similar to controls (17.8 vs. 17.4%) respectively (NS). CD patients
      exhibited frequencies of 8.8, 3.0 and 6.0% for the R702, G908R and L1007fs
      polymorphisms respectively, whereas our control population had allele frequencies
      of 11.6, 2.3 and 3.5% for the three mutations respectively (NS). We did not find
      any relationship between CARD15 mutations and the different phenotypes of Crohn s
      disease, according to Vienna classification. CONCLUSIONS: in our CD population,
      other factors (i.e. environmental), in addition to genetics, must be mainly
      involved in the development of the disease.

PMID- 18052660
TI  - Normal development of fetal hepatic haematopoiesis during the second trimester of
      gestation is upregulated by fibronectin expression in the stromal cells of the
      portal triads.
AB  - OBJECTIVE: in midtrimester fetuses the principal site of hematopoiesis is the
      liver. In hematopoietic organs, stromal cells such as fibroblasts, epithelial
      cells, and macrophage-like cells develop networks to maintain hematopoiesis, i.e.
      hematopoietic stem cell self-renewal, proliferation, and growth, by interaction
      with hematopoietic progenitor cells. ECM glycoproteins produced by the stromal
      cells are known to play a critical role in the regulation of cell growth and
      differentiation. Numerous soluble and membrane-bound factors directly regulating
      haematopoiesis have been documented, but little is known about fetal hepatic
      stromal cell activity and stromal extracellular matrix protein-fibronectin, on
      fetal hepatic haematopoiesis. The binding of late stage erythroid cells to
      fibronectin has been well characterized and is believed to be critical for the
      terminal stages of erythroid differentiation. The intention of this article is to
      determine the role of fibronectin in fetal hepatic hematopoietic proliferation
      and differentiation in different stages of development. MATERIAL AND METHOD: we
      examined and compared the immunohistochemical expression of fibronectin in the
      hepatic stromal portal fields in the 1st, 2nd, and 3rd trimester of gestation
      respectively, in relation to the appearance of CD34 progenitor hematopoietic,
      stromal progenitor and vascular endothelial positive cells. RESULTS: our results
      demonstrated a quantitative difference in the second trimester of gestation
      concerning the expression of fibronectin in the connective tissue stroma of the
      hepatic portal fields over the equivalent expression of the protein in the first
      (p < 0.0001, t-test) and third trimester (p < 0.0001, t-test). Similar changes in
      the above period were found concerning the expression of CD34 during the second
      trimester of gestation, over the first (p < 0.0001, t-test) and third trimesters
      (p < 0.0001, t-test), suggesting a direct involvement of fibronectin in the
      sustaining of hematopoietic activity. CONCLUSIONS: our data provide evidence that
      an ECM glycoprotein component, fibronectin, plays a relevant role in
      hematopoiesis through interaction between stromal cells and hematopoietic
      progenitor cells.

PMID- 18052661
TI  - [Old donors in liver transplantation for chronic hepatitis C].
AB  - BACKGROUND: the natural history of recurrent hepatitis C after liver
      transplantation (LT) is extremely variable, with progression to allograft failure
      in a substantial proportion of patients. The identification of factors associated
      with this poorer outcome may improve results. While donor age has been identified
      as one of the most important factors, the actual options to modify this variable
      are limited. OBJECTIVES: a) to describe the natural history of HCV(+) liver
      transplant recipients depending on donor age ( < or = 50 years), including
      clinical, biochemical, and histological outcomes; and b) to identify in the
      subgroup of organ recipients from aged donors (= 50 years) factors associated
      with an aggressive course. METHODS: a retrospective study of clinical and
      histological data including protocol liver biopsies for 162 HCV (+) liver
      transplant patients between 1997 and 2001 with at least one year of follow-up.
      Aggressive recurrent hepatitis C was defined as a progression to fibrosis > 1
      during the first year post-LT, development of a cholestatic form of recurrent
      hepatitis C, and /or graft failure due to HCV during the first five years post
      LT. Factors analyzed as potentially associated with recurrent hepatitis C
      included: a) recipient-related: demographics (age, sex), pre-transplantation
      (hepatocellular carcinoma, Child-Pugh classification, history of alcohol, HBV
      serological markers, antiviral treatment, nutritional status, biochemical
      variables); b) donor-related: demographics (age, sex), cause of death, grade of
      steatosis defined as minimal vs. moderate-severe > 10%); c) surgery-related: cold
      preservation and rewarming time, duration of procedure, blood transfusion; and d)
      post-LT management-related: immunosuppression, liver enzymes in the first 14 days
      post-LT, acute hepatitis post-LT, surgical complications (vascular and/or
      biliary). RESULTS: patients were divided into two groups according to donor age
      group 1 ( < 50 years), n = 83, 51%, and group 2 (= 50 years), n = 79, 49%).
      Median follow-up was 5 years (range: 3 months-8.5 years). Aggressive recurrent
      hepatitis C occurred significantly more frequently in the older donor group (64
      vs. 20.5%, p < 0.0001). In this group, potent immunosuppression -triple and
      quadruple regimens- (p = 0.04) and acute hepatitis post-LT (p = 0.03) were the
      only variables associated with aggressive recurrence. Degree of donor steatosis
      was not associated with the prognosis of recurrent hepatitis C. CONCLUSION: the
      use of aged donors is partly responsible for the accelerated progression of
      hepatitis C after LT. When old donors are used we should avoid over
      immunosuppression, and probably evaluate antiviral therapy in those with acute
      recurrent hepatitis C.

PMID- 18052662
TI  - [Perforation after colonoscopy: our 16-year experience].
AB  - OBJECTIVE: the aim of this retrospective study was to evaluate the incidence of
      colon perforations from diagnostic and therapeutic colonoscopies, and to assess
      their management in our hospital. PATIENTS AND METHOD: perforations resulting
      from colonoscopy in our hospital were reviewed for the period January, 1991 to
      December, 2006. The study analyzed: purpose of procedure, lesion mechanisms,
      clinical and radiological presentations, delays in diagnosis, patient status,
      therapeutic handling, and outcome. RESULT: fifteen perforations (0.09%) (9 males
      and 6 females) out of a total of 16,285 colonoscopies carried out were seen to
      have taken place during the study period. Nine of these occurred after diagnostic
      colonoscopies, and 6 occurred after therapeutic endoscopies. Around 60% of
      perforations were detected by the endoscopist while carrying out the procedure
      (88.6% during diagnostic endoscopy, and 16.6% during therapeutic endoscopy). In
      73.7% of cases abdominal pain and distension were the most frequent symptoms;
      extraluminal gas was seen in 100% of cases with imaging techniques. Delayed
      diagnosis (> 24 hours) occurred in 40% of patients (range: 1-6 days). Twelve
      patients were operated upon (80%), of whom 4 were ASA II and 8 were ASA III/IV.
      Postoperative morbidity was 44.44%, and mortality was 25%. The outcome of
      patients receiving conservative treatment was found to be satisfactory.
      CONCLUSION: perforation of the colon during colonoscopy is a rare complication
      with serious -even lethal- consequences. Conservative treatment can be provided
      for selected cases under strict clinical control. Type of surgery will depend on
      the lesion location and size, concomitant colon pathology, and degree of fecal
      contamination. Mortality seems to be related to general status rather than the
      surgical technique used.

PMID- 18052663
TI  - [Protocolized cognitive-behavioural group therapy for inflammatory bowel
      disease].
AB  - INTRODUCTION: patients affected by inflammatory bowel disease have a high rate of
      psychiatric disorders such as depression and anxiety. OBJECTIVE: the main goal of
      this study was to design, to put into practice, and to validate a protocolized
      psychological treatment program based on the coping model, and a psycho
      educational methodology in which the following intervention modules were included
      illness information, coping model, problem solving techniques, relaxation,
      social skill training, distraction, and cognitive restructuring techniques. All
      these techniques were adapted to the characteristic features of inflammatory
      bowel disease. METHOD: the sample included 57 patients with inflammatory bowel
      disease from the Spanish Crohn s Disease and Ulcerative Colitis Association. The
      sample was randomly assigned to one of the two experimental groups -33 were
      assigned to the treatment group, and 24 were assigned to the waiting list control
      group. RESULTS: the results reflected a significant clinical and statistical
      improvement in anxiety (p < 0.001) and depression (p < 0.001) variables when
      compared to the waiting list control group. Likewise, improvement was sustained
      at 3, 6, and 12 months during follow-up. CONCLUSION: the protocolized
      psychological treatment program, administered in group sessions, is effective in
      reducing emotional symptoms arising as a result of inflammatory bowel disease.

PMID- 18052664
TI  - [Bacterial DNA in patients with cirrhosis and sterile ascites. Its role as a
      marker of bacterial translocation and prognostic tool].
AB  - During the last decade, we have witnessed an increase in the amount of data
      related with the presence of bacterial translocation in experimental models of
      cirrhosis. However, clinical studies have been limited by the lack of non
      invasive methods to study this phenomenon. Over the past years, the research
      developed in our laboratory has been focused on the detection of bacterial DNA in
      serum and ascitic fluid of patients with cirrhosis and sterile ascites, the
      clinical and immunological implications of such finding. Initially, by means of a
      polymerase chain reaction (PCR)-based method and automated nucleotide sequencing,
      we were able to detect and identify the presence of fragments of bacterial DNA in
      the mentioned patients with culture-negative, non-neutrocytic ascites. Since
      then, we have accumulated a core of data suggesting that the presence of
      bacterial DNA may have an important role not only as a marker of bacterial
      translocation, but also as a short-term prognostic factor. Here, we discuss the
      past, present and future of this line of investigation.

PMID- 18052665
TI  - [Fistulizing Crohn's disease].

PMID- 18052666
TI  - [A 70-year-old man with colic pain on left upper quadrant of the abdomen and
      diffuse crepitation on the entire abdominal wall].

PMID- 18052667
TI  - Acute GI bleeding by multiple jejunal gastrointestinal autonomic nerve tumour
      associated with neurofibromatosis type I.
AB  - We describe a surgical emergency due to GI-bleeding caused by gastrointestinal
      autonomic nerve tumours (GANT s) in a patient with von Recklinghausen s disease.
      A 72 year old female patient with von Recklinghausen s disease was admitted with
      maelena. Endoscopy showed no active bleeding in the stomach and the colon.
      Therefore an angio-CT-scan was performed which revealed masses of the proximal
      jejunum as source of bleeding. Laparotomy was indicated and a 20 cm segment of
      jejunum which carried multiple extraluminal tumours was resected. The source of
      the bleeding was a 2 cm tumour which had eroded the mucosal surface.
      Immunohistologically, evidence of neuronal differentiation could be shown in the
      spindle-formed cells with positive staining for C-Kit (CD 117), CD 34, and a
      locally positive staining for synaptophysine and S100. This case report
      illustrates the association between neurofibromatosis and stromal tumours and
      should alert surgeons and gastroenterologist about gastrointestinal
      manifestations in patients with von Recklinghausen s disease.

PMID- 18052668
TI  - Chronic or recurrent appendicitis?

PMID- 18052669
TI  - Laparoscopic management of sigmoid colon intussusception caused by a malignant
      tumor: case report.

PMID- 18052670
TI  - [Giant villous adenoma with loss of electrolytes. Review of literature and
      current status].

PMID- 18052671
TI  - [Shift of the heart axis due to mediastinum recurrence of a retroperitoneal
      liposarcoma].

PMID- 18052672
TI  - [Gallbladder torsion].

PMID- 18052673
TI  - ["Body Packer" syndrome due to cocaine intoxication].

PMID- 18052674
TI  - Mechanisms of neurogenic pulmonary edema development.
AB  - Neurogenic pulmonary edema is a life-threatening complication, known for almost
      100 years, but its etiopathogenesis is still not completely understood. This
      review summarizes current knowledge about the etiology and pathophysiology of
      neurogenic pulmonary edema. The roles of systemic sympathetic discharge, central
      nervous system trigger zones, intracranial pressure, inflammation and anesthesia
      in the etiopathogenesis of neurogenic pulmonary edema are considered in detail.
      The management of the patient and experimental models of neurogenic pulmonary
      edema are also discussed.

PMID- 18052675
TI  - Modulation of antioxidant enzyme activities by sexual steroid hormones.
AB  - Taking into consideration the biological importance of interaction between
      antioxidant defense (AD) enzymes and sexual steroid hormones it was deemed
      important to compare our recent achievements in the field with the state of
      current knowledge. The main goal of the present review was to investigate the
      changes of AD enzyme activities: superoxide dismutases, catalase, glutathione
      peroxidase, glutathione-S-transferase and glutathione reductase in the brain of
      female and male rats depending on progesterone and estradiol. These ovarian
      steroids produce their effects by acting on numerous target tissues and organs,
      such as the reproductive organs, bone tissue and cartilage, peripheral blood
      vessels and the central nervous system (CNS). We have chosen it as a new
      parameter that might represent an important indicator of the changes within the
      CNS, bearing in mind the biological importance of the enzymes of the AD system.
      Our experimental results indicate that the AD enzyme activities in the brain
      tissue of female and male rats show a certain dependence on the concentration of
      progesterone and estradiol. The present review suggests that the modulation of
      the oxidative and antioxidative capacity by sexual steroid hormones is mediated
      through antioxidant metabolizing enzymes.

PMID- 18052676
TI  - Different secretory response of pancreatic islets and insulin secreting cell
      lines INS-1 and INS-1E to osmotic stimuli.
AB  - Objective of this study was to characterize osmotically-induced insulin secretion
      in two tumor cell lines. We compared response of freshly isolated rat pancreatic
      islets and INS-1 and INS-1E tumor cell lines to high glucose, 30 % hypotonic
      medium and 20 % hypertonic medium. In Ca(2+)-containing medium glucose induced
      insulin release in all three cell types. Hypotonicity induced insulin secretion
      from islets and INS-1 cells but not from INS-1E cells, in which secretion was
      inhibited despite similar increase in cell volume in both cell types. GdCl(3)
      (100 micromol/l) did not affect insulin response from INS-1E cells to hypotonic
      challenge. Hypertonic medium inhibited glucose-induced insulin secretion from
      islets but not from tumor cells. Noradrenaline (1 micromol/l) inhibited glucose
      induced but not swelling-induced insulin secretion from INS-1 cells.
      Surprisingly, perifusion with Ca(2+)-depleted medium showed distinct secretory
      response of INS-1E cells to hypotonicity while that of INS-1 cells was partially
      inhibited. Functioning glucose-induced insulin secretion is not sufficient
      prerequisite for hypotonicity-induced response in INS-1E cells suggesting that
      swelling-induced exocytosis is not essential step in the mechanism mediating
      glucose-induced insulin secretion. Both cell lines are resistant to inhibitory
      effect of hyperosmolarity on glucose-induced insulin secretion. Response of INS
      1E cells to hypotonicity is inhibited by the presence of Ca(2+) in medium.

PMID- 18052677
TI  - Effect of pedaling rates and myosin heavy chain composition in the vastus
      lateralis muscle on the power generating capability during incremental cycling in
      humans.
AB  - In this study, we have determined power output reached at maximal oxygen uptake
      during incremental cycling exercise (P(I, max)) performed at low and at high
      pedaling rates in nineteen untrained men with various myosin heavy chain
      composition (MyHC) in the vastus lateralis muscle. On separate days, subjects
      performed two incremental exercise tests until exhaustion at 60 rev min(-1) and
      at 120 rev min(-1). In the studied group of subjects P(I, max) reached during
      cycling at 60 rev min(-1) was significantly higher (p=0.0001) than that at 120
      rev min(-1) (287+/-29 vs. 215+/-42 W, respectively for 60 and 120 rev min(-1)).
      For further comparisons, two groups of subjects (n=6, each) were selected
      according to MyHC composition in the vastus lateralis muscle: group H with higher
      MyHC II content (56.8+/-2.79 %) and group L with lower MyHC II content in this
      muscle (28.6+/-5.8 %). P(I, max) reached during cycling performed at 60 rev min(
      1) in group H was significantly lower than in group L (p=0.03). However, during
      cycling at 120 rev min(-1), there was no significant difference in P(I, max)
      reached by both groups of subjects (p=0.38). Moreover, oxygen uptake (VO(2)),
      blood hydrogen ion [H(+)], plasma lactate [La(-)] and ammonia [NH(3)]
      concentrations determined at the four highest power outputs completed during the
      incremental cycling performed at 60 as well as 120 rev min(-1), in the group H
      were significantly higher than in group L. We have concluded that during an
      incremental exercise performed at low pedaling rates the subjects with lower
      content of MyHC II in the vastus lateralis muscle possess greater power
      generating capabilities than the subjects with higher content of MyHC II.
      Surprisingly, at high pedaling rate, power generating capabilities in the
      subjects with higher MyHC II content in the vastus lateralis muscle did not
      differ from those found in the subjects with lower content of MyHC II in this
      muscle, despite higher blood [H(+)], [La(-)] and [NH(3)] concentrations. This
      indicates that at high pedaling rates the subjects with higher percentage of MyHC
      II in the vastus lateralis muscle perform relatively better than the subjects
      with lower percentage of MyHC II in this muscle.

PMID- 18052678
TI  - Retinol-binding protein 4 expression in visceral and subcutaneous fat in human
      obesity.
AB  - Retinol binding protein 4 (RBP4) is a novel adipokine which might be involved in
      the development of insulin resistance. The aim of the study was to investigate
      the expression of RBP4 mRNA in subcutaneous and visceral fat depots and the
      relationship between RBP4 plasma and mRNA levels relative to indices of adiposity
      and insulin resistance. In 59 Caucasian women (BMI 20 to 49 kg/m(2)) paired
      samples of subcutaneous and visceral fat were obtained for RBP4, leptin and GLUT
      4 mRNA analysis using reverse transcription-quantitative PCR. Euglycemic
      hyperinsulinemic clamp and computed tomography scans were performed. RBP4 mRNA
      levels as well as GLUT 4 mRNA and leptin mRNA levels were lower (P<0.001, P<0.01
      and P<0.001, respectively) in visceral compared to subcutaneous fat. No
      differences were found in RBP4 mRNA expression in the two fat depots or in RBP4
      plasma levels between subgroups of non-obese subjects (n=26), obese subjects
      without metabolic syndrome (n=17) and with metabolic syndrome (n=16). No
      correlations between RBP4 mRNA or plasma levels relative to adiposity, glucose
      disposal rate and GLUT 4 mRNA expression in adipose tissue were found. There was
      a weak positive correlation between plasma RBP4 and plasma triglycerides (r =
      0.30, p<0.05) and between plasma RBP4 and blood glucose (r = 0.26, p<0.05).
      Regardless of the state of adiposity or insulin resistance, RBP4 expression in
      humans was lower in visceral than in subcutaneous fat. We found no direct
      relationship between either RBP4 mRNA or its plasma levels and the adiposity or
      insulin resistance.

PMID- 18052679
TI  - Cognac polyphenolic compounds increase bradykinin-induced nitric oxide production
      in endothelial cells.
AB  - We recently reported that in vitro Cognac polyphenolic compounds (CPC) induce NO
      dependent vasorelaxant effects and stimulate cardiac function. In the present
      study, we aim to investigate the effect of CPC on both nitric oxide (NO) and
      superoxide anions (O(2)(-)) production in cultured human endothelial cells. In
      addition, its effect on the bradykinin (BK)-induced NO production was also
      tested. The role and sources of O(2)(-) in the concomitant effect of BK plus CPC
      were pharmacologically determined. NO and O(2)(-) signals were measured using
      electron paramagnetic resonance technique using specific spin trappings. Both,
      CPC and BK induced an increase in NO production in human endothelial cells. The
      combination of both further enhanced NO release. The capacity of CPC plus BK to
      increase NO signal was blunted by the NO synthase inhibitor, N(G)-nitro-L
      arginine methyl ester, and was enhanced in the presence either of superoxide
      dismutase or catalase. Moreover, CPC plus BK response was greater after
      inhibition of either NADPH oxidase by apocynin or xanthine oxidase by allopurinol
      but it was not affected by rotenone. CPC did not affect O(2)(-) level either
      alone or after its increase upon lipopolysaccharide treatment. Finally, the
      capacity of BK alone to increase NO was enhanced either by apocynin or
      allopurinol. Altogether, these data demonstrate that CPC is able to directly
      increase NO production without affecting O(2)(-) and enhances the BK-induced NO
      production in human endothelial cells. The data highlight the ability of BK to
      stimulate not only NADPH oxidase- but also xanthine oxidase-inhibitor sensitive
      mechanisms that reduce its efficiency in increasing NO either alone or in the
      presence of CPC. These results bring pharmacological evidence for vascular
      protection by CPC via its potentiating effect of BK response in terms of
      endothelial NO release.

PMID- 18052680
TI  - The developmental changes in mitochondrial DNA content per cell in human cord
      blood leukocytes during gestation.
AB  - The mitochondrial DNA (mtDNA) amount in cells as the basis for mitochondrial
      energy generating system, which produces ATP, plays an important role in the
      fetal development and postnatal morbidity. Isolated human cord blood leukocytes
      (HCBL) contribute very little to the overall metabolic turnover, but they may
      serve as easily available marker cells for the study of the mtDNA amount changes
      in cord blood during fetal development. The aim of our study was to analyze the
      mtDNA amount in HCBL. HCBL were isolated from cord blood samples of 107 neonates
      born between the 25th and 41st week of gestation. The mtDNA amount was analyzed
      by the real-time PCR method. The significant negative correlations were found
      between the relative mtDNA amount in HCBL and gestational age (r = -0.54, p<0.01)
      and birth weight (r = -0.43, p<0.01), respectively. The results revealed that the
      mtDNA content per cell decreases in HCBL with progressing fetal development. This
      may be explained by gradual shift of the hematopoiesis from fetal liver to bone
      marrow during the second half of pregnancy presumably accompanied by decreasing
      cell volume of HCBL as it was shown similarly in red blood cells.

PMID- 18052681
TI  - Effect of exercise on augmented aortic vasoconstriction in the db/db mouse model
      of type-II diabetes.
AB  - We evaluated the effects of exercise on the vascular constrictor responses to
      alpha-adrenergic stimulation in the db/db mice. Twenty male db/db and their age
      matched wild-type (WT) mice were exercised (1 hour/day, five days a week). Mice
      were anesthetized 7 weeks later, thoracic aortae were mounted in wire myograph
      and constrictor responses to phenylephrine (PE, 1 nM-10 microM) were obtained.
      Citrate synthase activity measured in the thigh adductor muscle was significantly
      increased in db/db mice that were exercise trained. Maximal force generated by PE
      was markedly greater in db/db aortae and exercise did not attenuate this
      augmented contractile response. Vessels were incubated with inhibitors of nitric
      oxide synthase (L-NAME, 200 microM), endothelin receptors (bosentan, 10 microM),
      protein kinase C (PKC) (calphostin C, 5 microM), cyclooxygenase (indomethacin, 10
      microM) or Rho-kinase (Y-27632, 0.1 microM). Only calphostin-C normalized the
      augmented PE-induced constriction in db/db and db/db- exercised mice to that
      observed in WT (p<0.05). Cumulative additions of indolactam, a PKC activator,
      induced significantly greater constrictor responses in aortic rings of db/db mice
      compared to WT and exercise did not affect this response. Our data suggest that
      the augmented vasoconstriction observed in the aorta of db/db mice is likely due
      to increased PKC activity and that exercise do not ameliorate this increased PKC
      mediated vasoconstriction.

PMID- 18052682
TI  - Apolipoprotein E/intrauterine undernutrition interaction and hypercholesterolemia
      in children.
AB  - The inconsistency of data regarding intrauterine programming of cardiovascular
      risk factors may be largely caused by genetic predisposition and later lifestyle.
      We analyzed whether low birth weight and apolipoprotein E (Apo E) polymorphism
      participate in the onset of hypercholesterolemia in children. Our approach was
      based on hypothesis that genetically enhanced susceptibility of different
      individuals might influence the effects of intrauterine programming. Two groups
      were selected from 2000 children at the beginning of an ongoing study: high
      cholesterol group (HCG, n=67) and low-cholesterol group as a control (LCG, n=72).
      Both groups were divided into tertilles according to birth weight and we compared
      birth weight and apo E gene polymorphism between and within groups. The birth
      weight in HCG was 0.3 kg lower than the controls (p<0.001). The frequency of
      apoE4 was 31 % in HCG and only 10 % in LCG. The frequency of apoE4+ genotypes was
      not significantly different between tertilles based on birth weight in HCG. We
      suppose that intrauterine undernutrition, demonstrated by a lower birth weight,
      participates in the development of hypercholesterolemia already in childhood. The
      effects of low birth weight and the candidate gene - apoE, are synergic.

PMID- 18052683
TI  - Age-related changes of human balance during quiet stance.
AB  - Certain aspects of balance control change with age, resulting in a slight
      postural instability. We examined healthy subjects between 20-82 years of age
      during the quiet stance under static conditions: at stance on a firm surface
      and/or on a compliant surface with eyes either open or closed. Body sway was
      evaluated from centre of foot pressure (CoP) positions during a 50 sec interval.
      The seven CoP parameters were evaluated to assess quiet stance and were analyzed
      in three age groups: juniors, middle-aged and seniors. The regression analysis
      showed evident increase of body sway over 60 years of age. We found that CoP
      parameters were significantly different when comparing juniors and seniors in all
      static conditions. The most sensitive view on postural steadiness during quiet
      stance was provided by CoP amplitude and velocity in AP direction and root mean
      square (RMS) of statokinesigram. New physiological ranges of RMS parameter in
      each condition for each age group of healthy subjects were determined. Our
      results showed that CoP data from force platform in quiet stance may indicate
      small balance impairment due to age. The determined physiological ranges of RMS
      will be useful for better distinguishing between small postural instability due
      to aging in contrast to pathological processes in the human postural control.

PMID- 18052684
TI  - Importance of timing of magnesium administration in the isolated ischemic
      reperfused rat heart: role of K(ATP) channels.
AB  - There is a growing interest for the beneficial effect of magnesium (Mg) in
      cardiovascular disorders. A number of cardiovascular disorders including
      myocardial infarction, arrhythmias and congestive heart failure have been
      associated with low extra- cellular or intracellular concentrations of Mg. The
      efficiency of the preconditioning effect of Mg on cardiac function and infarct
      size in the globally ischemic-reperfused isolated rat heart was studied together
      with the role of ATP-sensitive potassium (K(ATP)) channels in protection induced
      by Mg. Rat hearts were Langendorff perfused, subjected to 30 min of global
      ischemia and 90 min of reperfusion, including treatment groups which focused on
      different times of Mg (8 mmol/l) use. Infarct size was measured by
      triphenyltetrazolium chloride (TTC) method. The left ventricular function was
      assessed by left ventricular developed pressure (LVDP), heart rate (HR) and
      coronary flow (CF). The administration of Mg before ischemia had an anti-infarct
      effect in rat hearts and improved cardiac function. The protective effects of
      magnesium was abolished by the blocking of K(ATP) channels and suggests that K
      ATP channel has an important role in the heart protection effect of Mg as a
      preconditioning agent.

PMID- 18052685
TI  - Hyperlipidemia is associated with altered levels of insulin-like growth factor-I.
AB  - Previous studies revealed altered levels of the circulating insulin-like growth
      factor-I (IGF-I) and of its binding protein-3 (IGFBP-3) in subjects with coronary
      atherosclerosis, metabolic syndrome and premature atherosclerosis. Hyperlipidemia
      is a powerful risk factor of atherosclerosis. We expected IGF-I and IGFBP-3
      alterations in subjects with moderate/severe hyperlipidemia but without any
      clinical manifestation of atherosclerosis. Total IGF-I and IGFBP-3 were assessed
      in 56 patients with mixed hyperlipidemia (MHL; cholesterol >6.0 mmol/l,
      triglycerides >2.0 mmol/l), in 33 patients with isolated hypercholesterolemia
      (IHC; cholesterol >6.0 mmol/l, triglycerides <2.0 mmol/l), and in 29 healthy
      controls (cholesterol<6.0 mmol/l, triglycerides<2.0 mmol/l). The molar ratio of
      IGF-I/IGFBP-3 was used as a measure of free IGF-I. IHC subjects differed from
      controls by lower total IGF-I (164+/-60 vs. 209+/-73 ng/ml, p=0.01) and IGF-I
      /IGFBP-3 ratio (0.14+/-0.05 vs. 0.17+/-0.04, p=0.04). Compared to controls, MHL
      subjects had lower total IGF-I (153+/-54 ng/ml, p=0.0002) and IGFBP-3 (2.8+/-0.6
      mg/ml, p<0.0001), but higher IGF-I/IGFBP-3 ratio (0.25+/-0.06, p<0.0001).
      Differences remained significant after the adjustment for clinical and
      biochemical covariates, except for triglycerides. Patients with both IHC and MHL
      have lower total IGF-I compared to controls. The mechanism is presumably
      different in IHC and MHL. Because of prominent reduction of IGFBP-3 in patients
      with MHL, they have reduced total IGF-I despite the actual elevation IGF-I/IGFBP
      3 ratio as a surrogate of free IGF-I.

PMID- 18052686
TI  - Increased angiotensinogen production in epicardial adipose tissue during cardiac
      surgery: possible role in a postoperative insulin resistance.
AB  - Critical illness induces among other events production of proinflammatory
      cytokines that in turn interfere with insulin signaling cascade and induce
      insulin resistance on a postreceptor level. Recently, local renin-angiotensin
      system of adipose tissue has been suggested as a possible contributor to the
      development of insulin resistance in patients with obesity. The aim of our study
      was to determine local changes of the renin-angiotensin system of subcutaneous
      and epicardial adipose tissue during a major cardiac surgery, which may serve as
      a model of an acute stress potentially affecting endocrine function of adipose
      tissue. Ten patients undergoing elective cardiac surgery were included into the
      study. Blood samples and samples of subcutaneous and epicardial adipose tissue
      were collected at the beginning and at the end of the surgery. Blood glucose,
      serum insulin and adiponectin levels were measured and mRNA for angiotensinogen,
      angiotensin-converting enzyme and angiotensin II type 1 receptor were determined
      in adipose tissue samples using RT PCR. Cardiac surgery significantly increased
      both insulin and blood glucose levels suggesting the development of insulin
      resistance, while serum adiponectin levels did not change. Expression of
      angiotensinogen mRNA significantly increased in epicardial adipose tissue at the
      end of surgery relative to baseline but remained unchanged in subcutaneous
      adipose tissue. Fat expression of angiotensin-converting enzyme and type 1
      receptor for angiotensin II were not affected by surgery. Our study suggests that
      increased angiotensinogen production in epicardial adipose tissue may contribute
      to the development of postoperative insulin resistance.

PMID- 18052687
TI  - The effect of lipoic acid on antioxidant status and lipid peroxidation in rats
      exposed to chronic restraint stress.
AB  - This study was designed to investigate effect of alpha-lipoic acid (LA) on lipid
      peroxidation, nitric oxide production and antioxidant systems in rats exposed to
      chronic restraint stress. Twenty four male Wistar rats, aged three months, were
      divided into four groups: control (C), the group treated with LA (L), the group
      exposed to restraint stress (S) and the group exposed to stress and treated with
      LA (LS). Restraint stress was applied for 21 days (1 h/day) and LA (100
      mg/kg/day) was injected intraperitonally to the L and LS groups for the same
      period. Restraint stress significantly decreased brain copper/zinc superoxide
      dismutase (Cu,Zn-SOD) and brain and retina glutathione peroxidase (GSH-Px) and
      catalase (CAT) activities compared with the control group. Thiobarbituric acid
      reactive substances (TBARS), nitrite and nitrate levels were significantly
      increased in the tissues of the S group compared with the C group. LA produced a
      significant decrease in brain and retina TBARS, nitrite and nitrate levels of the
      L and LS groups compared to their corresponding control groups. LA increased all
      enzyme activities in the tissues of the LS group compared to the S group. Our
      study indicated that LA is an ideal antioxidant candidate for the prevention of
      stress-induced lipid peroxidation.

PMID- 18052688
TI  - Chronic atropine administration diminishes the contribution of vasoactive
      intestinal polypeptide to heart rate regulation.
AB  - Vasoactive intestinal polypeptide (VIP) is implicated in the modulation of vagal
      effects on the heart rate. In this study, the impact of acute and chronic
      atropine administration on VIP levels in rat heart atria was investigated in
      relation to heart rate in the course of vagus nerves stimulation. Anaesthetised
      control and atropinised (10 mg/kg/day for 10 days) rats pretreated with
      metipranolol and phentolamine that were either given or not a single dose of
      atropine were subjected to bilateral vagus nerve stimulation (30 min: 0.7 mA, 20
      Hz, 0.2 ms). VIP concentrations in the atria were determined after each
      stimulation protocol. In control rats with or without single atropine
      administration, the heart rate upon vagal stimulation was higher than in
      atropinised animals with or without single atropine dose, respectively. VIP
      concentrations in the control atria were significantly decreased after the
      stimulation; the decrease was comparable both in the absence and presence of a
      single dose of atropine. Compared to controls, VIP levels were significantly
      decreased after chronic atropine treatment and they were not further reduced by
      vagal stimulation and single atropine administration. Administration of VIP
      antagonist completely abolished the differences in the heart rate upon vagal
      stimulation between control and atropinised groups. In conclusion, the data
      indicate that chronic atropine administration affects VIP synthesis in rat heart
      atria and consequently it modifies the heart rate regulation.

PMID- 18052689
TI  - In vitro hypoxia increases production of matrix metalloproteinases and tryptase
      in isolated rat lung mast cells.
AB  - Chronic hypoxia results in hypoxic pulmonary hypertension characterized by
      fibrotization and muscularization of the walls of peripheral pulmonary arteries.
      This vessel remodeling is accompanied by an increase in the amount of lung mast
      cells (LMC) and the presence of small collagen cleavage products in the vessel
      walls. We hypothesize that hypoxia activates LMC, which release matrix
      metalloproteinases (MMPs) cleaving collagen and starting increased turnover of
      connective tissue proteins. This study was designed to determine whether in vitro
      hypoxia stimulates production of MMPs in rat LMC and increases their
      collagenolytic activity. The LMC were separated on the Percoll gradient and then
      were divided into two groups and cultivated for 24 h in 21 % O(2) + 5 % CO(2) or
      in 10 % O(2) + 5 % CO(2). Presence of the rat interstitial tissue collagenase
      (MMP-13) in LMC was visualized by immunohistological staining and confirmed by
      Western blot analysis. Total MMPs activity and tryptase activity were measured in
      both cultivation media and cellular extracts. Exposure to hypoxia in vitro
      increased the amount of cells positively labeled by anti-MMP-13 antibody as well
      as activities of all measured enzymes. The results therefore support the concept
      that LMC are an important source of increased collagenolytic activity in chronic
      hypoxia.

PMID- 18052690
TI  - The effects of head cooling on endurance and neuroendocrine responses to exercise
      in warm conditions.
AB  - The present study investigated the effects of head cooling during endurance
      cycling on performance and the serotonergic neuroendocrine response to exercise
      in the heat. Subjects exercised at 75 % VO(2max) to volitional fatigue on a cycle
      ergometer at an ambient temperature of 29+/-1.0 degrees C, with a relative
      humidity of approximately 50 %. Head cooling resulted in a 51 % (p<0.01)
      improvement in exercise time to fatigue and Borg Scale ratings of perceived
      exertion were significantly lower throughout the exercise period with cooling
      (p<0.01). There were no indications of peripheral mechanisms of fatigue either
      with, or without, head cooling, indicating the importance of central mechanisms.
      Exercise in the heat caused the release of prolactin in response to the rise in
      rectal temperature. Head cooling largely abolished the prolactin response while
      having no effect on rectal temperature. Tympanic temperature and sinus skin
      temperature were reduced by head cooling and remained low throughout the
      exercise. It is suggested that there is a co-ordinated response to exercise
      involving thermoregulation, neuroendocrine secretion and behavioural adaptations
      that may originate in the hypothalamus or associated areas of the brain. Our
      results are consistent with the effects of head cooling being mediated by both
      direct cooling of the brain and modified cerebral artery blood flow, but an
      action of peripheral thermoreceptors cannot be excluded.

PMID- 18052691
TI  - Mutation analysis of candidate genes SCN1B, KCND3 and ANK2 in patients with
      clinical diagnosis of long QT syndrome.
AB  - The long QT syndrome (LQTS) is a monogenic disorder characterized by prolongation
      of the QT interval on electrocardiogram and syncope or sudden death caused by
      polymorphic ventricular tachycardia (torsades de pointes). In general, mutations
      in cardiac ion channel genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2) have been
      identified as a cause for LQTS. About 50-60 % of LQTS patients have an
      identifiable LQTS causing mutation in one of mentioned genes. In a group of 12
      LQTS patients with no identified mutations in these genes we have tested a
      hypothesis that other candidate genes could be involved in LQTS pathophysiology.
      SCN1B and KCND3 genes encode ion channel proteins, ANK2 gene encodes cytoskeletal
      protein interacting with ion channels. To screen coding regions of genes SCN1B,
      KCND3, and 10 exons of ANK2 following methods were used: PCR, SSCP, and DNA
      sequencing. Five polymorphisms were found in screened candidate genes, 2
      polymorphisms in KCND3 and 3 in SCN1B. None of found polymorphisms has coding
      effect nor is located close to splice sites or has any similarity to known
      splicing enhancer motifs. Polymorphism G246T in SCN1B is a novel one. No mutation
      directly causing LQTS was found. Molecular mechanism of LQTS genesis in these
      patients remains unclear.

PMID- 18052693
TI  - Osseointegrated implants in subjects treated for generalized aggressive
      periodontitis: 10-year results of a prospective, long-term cohort study.
AB  - BACKGROUND: The aim of this prospective 10-year study of partially edentulous
      subjects treated for generalized aggressive periodontitis and periodontally
      healthy subjects was a clinical, microbiologic, and radiographic comparison of
      teeth and implants and assessment of the implants' success rate. METHODS: Five
      subjects treated for generalized aggressive periodontitis (GAgP) and five
      periodontally healthy subjects who were orally rehabilitated with osseointegrated
      implants participated in the study. First, they were examined 2 to 4 weeks before
      extraction of the non-retainable teeth (baseline) and 3 weeks after insertion of
      the final abutments. All further examinations were performed during a 3-month
      recall schedule over a 10-year period. At every session, clinical parameters were
      recorded, and the composition of the subgingival microflora was determined.
      Radiographs were taken at baseline after insertion of the superstructure and 1,
      3, 5, 8, and 10 years later. RESULTS: Throughout the follow-up period, the peri
      implant gingival index of GAgP subjects was significantly higher than in
      periodontally healthy subjects. There was no difference in plaque index between
      teeth and implants or between the two groups. The peri-implant probing depths
      were comparable in the two groups and remained < or =4 mm throughout the follow
      up. The probing depth was significantly higher around the teeth of the GAgP
      subjects compared to periodontally healthy subjects. Implants of GAgP subjects
      showed a significantly higher attachment loss (O 2.4 mm). The attachment level at
      teeth and implants of the periodontally healthy subjects and at teeth of the GAgP
      subjects was almost unchanged. Microbiologically, GAgP subjects had fewer cocci
      and more motile rods and filaments at teeth and implants than periodontally
      healthy subjects. GAgP subjects showed significantly more peri-implant bone loss
      in the first year (O 2.07 mm) and in the subsequent 9 years (total 1.3 mm). Bone
      loss at teeth also was significantly higher at baseline (O 26.39%) and in the
      following years (total 9.3%). Implant survival rates were 100% in periodontally
      healthy subjects versus 83.33% in GAgP subjects. CONCLUSIONS: This 10-year study
      showed that partially edentulous subjects treated for GAgP can be rehabilitated
      successfully with osseointegrated implants. However, the bone and attachment loss
      at the implants were higher than in periodontally healthy subjects.

PMID- 18052694
TI  - The efficacy of subgingival calculus removal with endoscopy-aided scaling and
      root planing: a study on multirooted teeth.
AB  - BACKGROUND: The dental endoscope was developed to facilitate visualization of the
      subgingival environment as an aid in diagnosis and non-surgical root debridement.
      The purpose of this study was to determine whether endoscopy-aided scaling and
      root planing (SRP) resulted in a greater reduction of residual calculus compared
      to SRP alone in multirooted teeth. METHODS: Twenty-four patients were enrolled
      and contributed 35 tooth pairs (70 teeth in total). Each tooth per pair was
      randomly assigned to receive endoscopy-aided SRP (test) or SRP alone (control).
      Both teeth were extracted immediately after treatment, washed with water, and
      stained with methylene blue. The percentage of residual calculus was determined
      via stereomicroscopy and digital image software by a single masked examiner.
      RESULTS: Overall, there was 1.16% (P = 0.097) less residual calculus at test
      versus control sites. At interproximal surfaces, test roots had 2.63% less
      residual calculus than control roots (P = 0.003), whereas test roots had slightly
      more residual calculus than controls at buccal/lingual surfaces (0.36%; P =
      0.652). There were no statistically significant differences in residual calculus
      between groups at deeper probing depths or at sites with deep furcation
      invasions. Only at shallower interproximal sites with probing depths < or =6 mm
      was significantly less residual calculus seen in roots treated with endoscopy (P
      = 0.020). Treatment time decreased significantly as operator experience
      increased; however, no significant improvement in residual calculus levels was
      noted with greater experience. CONCLUSION: Within the confines of this study, the
      use of the endoscope as an adjunct to traditional SRP provided no significant
      improvement in calculus removal in multirooted molar teeth.

PMID- 18052695
TI  - Retention of hopeless teeth: the effect on the adjacent proximal bone following
      periodontal surgery.
AB  - BACKGROUND: Clinical wisdom often suggests that retention of periodontally
      hopeless teeth may accelerate the destruction of the adjacent periodontium. The
      purpose of this study was to examine the effect of retaining hopeless teeth on
      the adjacent alveolar bone following periodontal surgery. METHODS: A
      retrospective study was conducted based on intraoral radiographs. Teeth were
      considered hopeless if they had lost > or =70% bone height at either of the
      proximal surfaces. The minimal follow-up period after surgery was 24 months. All
      subjects completed periodontal therapy, including scaling and root planing (SRP),
      and periodontal surgery at these sites. Ninety-three subjects with 110 hopeless
      teeth were included in this study. Cases were sorted into two groups: retained,
      which included 57 hopeless teeth (50 subjects) that were maintained; and
      extracted, which included 53 hopeless teeth (43 subjects) that were removed at
      surgery. All radiographs were digitized, and measurements of radiographic bone
      distance (RBD) were made using computerized software. RESULTS: Mean follow-up was
      4.40 +/- 0.23 years. For the retained hopeless teeth, there was a mean bone gain
      of 0.82 mm from baseline (7.18 +/- 0.35 mm) to the final examination (6.45 +/-
      0.41 mm; P = 0.0061). Likewise, the postoperative percentage of RBD of the
      retained hopeless teeth showed a statistically significant improvement from
      baseline (57.46% +/- 1.5%) to the final examination (52.32% +/- 2.03%; P =
      0.0032). Teeth adjacent to a hopeless tooth had a slight radiographic bone gain
      postoperatively, which was greater in the extracted group. However, it was
      significant only for the distal neighboring teeth (1.50% versus 11.36%,
      respectively; P = 0.0119). CONCLUSION: Long-term preservation of hopeless teeth
      following periodontal surgery is an attainable goal with no detrimental effect on
      the adjacent proximal teeth.

PMID- 18052696
TI  - Removable prostheses may enhance marginal bone loss around dental implants: a
      long-term retrospective analysis.
AB  - BACKGROUND: The aim of the study was to retrospectively evaluate marginal bone
      loss (MBL) around rough-surface dental implants, placed in a private clinic, and
      to construct a multivariate model based on formerly proposed prognostic
      variables. METHODS: Records of patients who were treated previously with dental
      implants were reviewed. The patients' latest annual clinical examinations and
      radiograms were used for data collection and the calculation of MBL. A patient
      based multivariate model was constructed based on two successive iterations of
      statistical analysis. RESULTS: Eighty-two patients and 265 implants with > or =30
      months of follow-up were evaluated. The overall survival rate was 95.8% (2.6%
      early loss and 1.5% late loss). By evaluating the data with the single implant as
      a unit of analysis, MBL was correlated with time. Higher MBL values were found in
      smokers and around implants supporting removable prostheses. In the patient-based
      analysis, only smoking and the presence of a removable prosthesis correlated with
      higher values of MBL. Odds ratios for higher rates of MBL were 1.95 and 2.57 for
      smokers and around removable prostheses, respectively. Neither time nor any of
      the other suspected variables correlated with higher MBL. CONCLUSIONS: The
      present study corroborated the notion that smoking correlates with higher MBL and
      implied that implants supporting removable prostheses tend to display more bone
      loss. Further studies are needed to elucidate the latter finding.

PMID- 18052697
TI  - Morphometric study of the interproximal unit in the esthetic region to correlate
      anatomic variables affecting the aspect of soft tissue embrasure space.
AB  - BACKGROUND: The presence of a normal papilla is crucial to avoid the unpleasant
      esthetic defects that are of major concern to periodontists, restorative
      dentists, and patients. During the course of progressive periodontitis and
      following periodontal treatment, it is not uncommon to have a partial loss of the
      interdental papilla. This loss can lead to an unesthetic gingival appearance.
      This study evaluated different anatomic variables in an effort to determine their
      role in the papillary appearance of maxillary incisors. METHODS: A total of 178
      interdental embrasures in 58 patients were selected randomly for examination. For
      each patient, a digital photograph and a modified periapical radiograph of the
      interdental embrasure of the four maxillary incisors were taken by using a
      special metric device fixed to a centrator as a reference marker. Clinical and
      radiographic data were obtained for the distance from the contact point to the
      alveolar crest and for the interradicular distance. We used a classification
      system with regard to peri-implant soft tissue based on esthetic assessments
      related to the space between reference lines through the highest gingival
      curvature of the crown-tooth margin and the contact point. RESULTS: In the group
      of interdental sites with an interradicular distance of less than approximately
      2.4 mm, an increase in the distance between the contact point and the bone crest
      corresponded to a marked increase in the interdental black triangle's dimensions
      and, therefore, a less esthetic smile. In particular, when the interradicular
      distance was >2.4 mm, we statistically estimated that the other anatomic variable
      considered, the distance from the contact point to the alveolar crest, lost its
      influence on whether the interdental papilla would be present or absent.
      CONCLUSION: The interradicular distance and the distance between the contact
      point and the alveolar crest have independent and combined effects on the
      presence or absence of the interdental papilla.

PMID- 18052698
TI  - Intrauterine growth restriction, low birth weight, and preterm birth: adverse
      pregnancy outcomes and their association with maternal periodontitis.
AB  - BACKGROUND: It has been suggested that periodontitis is associated with systemic
      alterations such as adverse pregnancy outcomes. However, some conflicting results
      have been reported. This case-control study was conducted to determine the
      association between maternal periodontitis and preterm birth (PTB), low birth
      weight (LBW), and intrauterine growth restriction (IUGR). METHODS: A total of
      1,305 Brazilian women from multiethnic groups were enrolled and divided into four
      groups: control group (1,042 women who gave birth to infants with adequate
      gestational age and birth weight); PTB group (238 women, gestational age <37
      complete weeks); LBW group (235 women, birth weight <2,500 g); and IUGR group (77
      women who gave birth to infants with fetal growth retardation). Periodontitis was
      defined as the presence of at least four teeth with one or more sites with
      probing depth > or =4 mm and clinical attachment loss > or =3 mm. The effects of
      variables of interest, confounders, and interaction were tested through
      univariate and multivariate logistic regression tests. RESULTS: After adjusting
      for variables of interest, maternal periodontitis was retained in the final model
      for PTB (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.12 to 2.59), LBW
      (OR = 1.67; 95% CI: 1.11 to 2.51), and IUGR (OR = 2.06; 95% CI: 1.07 to 4.19).
      When the interaction between periodontitis and previous PTB was tested, an OR of
      5.94 (P <0.001), 9.12 (P <0.001), and 18.90 (P <0.001) was observed for PTB, LBW,
      and IUGR, respectively. CONCLUSIONS: Maternal periodontitis is associated with an
      increased risk for PTB, LBW, and IUGR. Results emphasize the importance of
      periodontal care in prenatal health programs.

PMID- 18052699
TI  - Use of anorganic bovine-derived hydroxyapatite matrix/cell-binding peptide (P-15)
      in the treatment of class II furcation defects: a clinical and radiographic study
      in humans.
AB  - BACKGROUND: This study compared clinical and radiographic findings for the
      treatment of Class II furcation defects in human mandibular molars using
      anorganic bovine-derived hydroxyapatite matrix (ABM)/cell-binding peptide (P-15)
      or open flap debridement (OFD). METHODS: Twelve subjects showing two comparable
      Class II furcation defects in their mandibular molars were enrolled. The defects
      in each subject were assigned randomly to the test (ABM/P-15) or the control
      (OFD) group. Clinical measurements and standardized radiographs were taken at
      baseline and 6 to 7 months after surgery. RESULTS: There were no statistically
      significant differences between the test and control groups for any clinical or
      radiographic parameter (P >0.05). On comparing the baseline and final
      measurements, the gain in horizontal clinical attachment level and reduction in
      gingival recession were significant only in the test group (P < or =0.02),
      whereas the gain in the vertical clinical attachment level was significant in
      both groups (P < or =0.04). In the test group, four of 12 sites showed complete
      closure, and five showed partial closure; in the control group, three defects
      showed complete closure, and four showed partial closure (P = 0.42). Subtraction
      radiography revealed similar gains in bone height and increases in mean bone
      density with both treatments (P >0.05). CONCLUSIONS: ABM/P-15 yielded favorable
      results in the treatment of Class II furcation defects over a 6-month evaluation
      period; however, there was no difference compared to OFD. Further studies using a
      larger sample size are needed to confirm the present findings.

PMID- 18052700
TI  - Comparison of analgesic and anti-inflammatory efficacy of selective and non
      selective cyclooxygenase-2 inhibitors in dental implant surgery.
AB  - BACKGROUND: The analgesic and anti-inflammatory efficacy of tenoxicam and
      meloxicam were evaluated in this double-masked, randomized, prospective study by
      analyzing pain scores and the need for rescue-analgesic agents following dental
      implant surgery. METHODS: One hundred patients, in whom 241 dental implants were
      placed, were divided into two groups. For 4 days beginning the day before
      surgery, the first group received meloxicam, 15 mg daily, and the second group
      received tenoxicam, 20 mg daily, followed by 1 hour preoperatively and for 2 days
      thereafter. Pain intensity was rated by the subjects based on a visual analog
      scale on the operation day and on the following 6 days. The patients were
      recommended to use a rescue analgesic if the pain score was > or =4.
      Postoperative complications, such as edema, hematoma, infection, severe pain,
      paresthesia, or gastrointestinal complaints, were also noted. RESULTS:
      Statistical analysis revealed that 54% of patients in the tenoxicam group and 66%
      of patients in the meloxicam group used rescue analgesics on day 1. However, the
      difference between the groups was not significant (chi(2) = 1.05; P = 0.30). The
      relationship between the reduction of consumption and time was not significant in
      either group (Z = 0.84; P = 0.40). The relationship between the use of rescue
      analgesics and the number of implants placed was not significant. Among patients
      who reported postoperative complications, there was not a statistically
      significant difference between the groups (chi(2) = 0.04; P = 0.84). CONCLUSION:
      Meloxicam and tenoxicam exhibited a similar analgesic and anti-inflammatory
      efficacy in the present investigation.

PMID- 18052701
TI  - Markers of systemic bacterial exposure in periodontal disease and cardiovascular
      disease risk: a systematic review and meta-analysis.
AB  - BACKGROUND: Recent meta-analyses reported a weak association between periodontal
      disease (PD) on clinical examination and cardiovascular disease (CVD). Systemic
      bacterial exposure from periodontitis, which correlates poorly with the clinical
      examination, has been proposed as the more biologically pertinent risk factor.
      The purpose of this study was to review and analyze the association between PD
      with elevated systemic bacterial exposure and CVD. METHODS: We searched in the
      PubMed, Cochrane Controlled Trials Register, EMBASE, and SCOPUS databases for all
      literature examining PD and CVD. From 10 selected publications, we extracted 12
      cohort (N = 5) and cross-sectional (N = 7) studies and included 11 of these in a
      meta-analysis. With stratified analyses, this resulted in 14 analyses of coronary
      heart disease (CHD; N = 7), stroke (N = 4), and carotid intima-medial thickening
      (CIMT; N = 3) as a measure of early atherosclerosis. Systemic bacterial exposure
      was measured by periodontal bacterial burden (N = 1), periodontitis-specific
      serology (N = 12), or C-reactive protein (N = 1). RESULTS: Periodontal disease
      with elevated markers of systemic bacterial exposure was associated strongly with
      CHD compared to subjects without PD, with a summary odds ratio of 1.75 (95%
      confidence interval (CI): 1.32 to 2.34; P <0.001). This group was not associated
      with CVD events or with stroke but was associated with a significant increase in
      mean CIMT (0.03 mm; 95% CI: 0.02 to 0.04). CONCLUSION: Periodontal disease with
      elevated bacterial exposure is associated with CHD events and early atherogenesis
      (CIMT), suggesting that the level of systemic bacterial exposure from
      periodontitis is the biologically pertinent exposure with regard to
      atherosclerotic risk.

PMID- 18052702
TI  - Subgingival human cytomegalovirus correlates with increased clinical periodontal
      parameters and bacterial coinfection in periodontitis.
AB  - BACKGROUND: Viruses from the Herpesviridae family may be implicated in the
      pathogenesis of periodontal disease. The aim of this investigation was to compare
      the subgingival frequency of human cytomegalovirus (HCMV) in subjects affected by
      periodontitis to periodontally healthy subjects and to assess the correlation of
      HCMV with periodontal clinical parameters and periodontopathic bacteria. METHODS:
      Thirty subjects with periodontitis (20 with chronic periodontitis and 10 with
      aggressive periodontitis) were included in the study. A group of 22 periodontally
      healthy individuals served as controls. Clinical periodontal parameters of
      probing depth (PD) and clinical attachment level (CAL) were recorded using a
      computerized periodontal probe. Subgingival plaque samples were processed for
      viral identification by nested polymerase chain reaction and bacterial
      identification by culture. Clinical periodontal parameters, frequency of
      detection of HCMV, and microbial composition were compared between the groups
      using the two-tailed Student t, chi(2), and Mann-Whitney tests. Logistic and
      linear regression analyses were performed to measure the association between
      virus-bacterial coinfection and clinical parameters (P < or =0.05). RESULTS: HCMV
      detection was more prevalent (P < or =0.05) in periodontally diseased subjects
      compared to healthy ones. Furthermore, in all groups, PD and CAL were increased
      in HCMV-positive sites. In the periodontitis groups, higher frequencies and
      levels of specific periodontopathic bacteria were detected in HCMV-positive
      sites. CONCLUSIONS: HCMV detection in periodontal pockets was associated with
      higher levels of periodontopathic bacteria and increased PD and CAL at sampled
      sites. HCMV/bacteria coinfection may be an important factor in periodontal
      destruction.

PMID- 18052703
TI  - The interleukin-1 and Fcgamma receptor gene polymorphisms in Japanese patients
      with rheumatoid arthritis and periodontitis.
AB  - BACKGROUND: The pathobiology of rheumatoid arthritis (RA) is similar to that of
      periodontitis in that proinflammatory cytokines and immunoglobulin G Fc receptor
      (FcgammaR) play an important role. Functional polymorphisms of interleukin (IL)-1
      and FcgammaR were shown to be associated with susceptibility to both diseases.
      Therefore, we evaluated whether the IL-1 and FcgammaR gene polymorphisms
      represent a common risk factor for RA and periodontitis. METHODS: The study
      population consisted of Japanese adults with RA (RA group; N = 100),
      periodontitis only (P group; N = 100), and healthy individuals with no systemic
      or oral disease (H group; N = 100). Clinical periodontal condition was defined by
      measurements of probing depth, clinical attachment level, and bleeding on
      probing. Genomic DNA was isolated from peripheral blood and analyzed for
      determination of IL-1 genotypes (IL-1A+4845, IL-1B+3954, and IL-1RN+2028) and
      FcgammaR genotypes (FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB) by allele
      specific polymerase chain reactions. RESULTS: Among 100 patients with RA, 86%
      showed periodontal tissue destruction. However, the RA group exhibited milder
      levels of periodontal tissue destruction than the P group (P <0.01). There was a
      significant difference in the distribution of IL-1B+3954 C/T genotypes between
      the RA and P groups and between the RA and H groups (P = 0.03 for both
      comparisons), with enrichment of the T allele in the RA group (P = 0.04; odds
      ratio, 2.9 for both comparisons). The combination of IL-1A+4845 T and IL-1+3954 T
      alleles yielded a strong association with RA and periodontitis (RA versus P
      group: P = 0.00001; RA versus H group: P = 0.00001). CONCLUSIONS: These results
      failed to show that IL-1 and FcgammaR gene polymorphisms constitute a common risk
      factor for RA and periodontitis. However, it was suggested that the distributions
      of IL-1B+3954 genotypes and IL-1A+4845 and IL-1B+3954 haplotypes were unique to
      the patients with RA and periodontitis.

PMID- 18052704
TI  - Evaluation of gingival crevicular fluid and serum levels of high-sensitivity C
      reactive protein in chronic periodontitis patients with or without coronary
      artery disease.
AB  - BACKGROUND: Most studies have evaluated serum C-reactive protein (CRP) levels in
      chronic periodontitis (CP) patients, and a few investigations have examined
      gingival crevicular fluid (GCF) CRP levels. The aims of this study were to
      determine GCF and serum levels of high-sensitivity CRP (HsCRP) in CP patients
      with or without coronary artery disease (CAD) and to investigate the relationship
      between the GCF and serum HsCRP levels in CP patients with and without CAD.
      METHODS: Thirty CP patients with angiographically proven CAD, 20 CP patients, and
      17 healthy individuals were included in the study. Clinical parameters were
      recorded, and serum and GCF samples were collected. The level of HsCRP in GCF was
      assayed by a high-sensitivity enzyme-linked immunosorbent assay. The HsCRP level
      was assayed in the plasma on a nephelometer. RESULTS: The serum HsCRP levels were
      significantly higher in CP patients with or without CAD than in the control
      group, and there was a correlation between serum HsCRP levels and clinical
      parameters and between serum HsCRP levels and GCF volume. There was no
      statistically significant difference in GCF HsCRP levels between the groups.
      There was no correlation between GCF HsCRP levels and clinical parameters, GCF
      volume, or serum HsCRP levels. CONCLUSIONS: Patients with CP and CP + CAD had
      statistically significant elevations in serum HsCRP levels compared to healthy
      subjects. However, HsCRP levels of GCF did not differ from those of the control
      and CP groups or the control and CP + CAD groups. Further studies are needed to
      clarify the relationship between GCF CRP levels and periodontal diseases.

PMID- 18052705
TI  - Gingival crevicular fluid levels of leukotriene B4 in periodontal health and
      disease.
AB  - BACKGROUND: Leukotriene B(4) (LTB(4)) is a membrane-derived lipid mediator formed
      from arachidonic acid. LTB(4) is among the most potent stimulants of
      polymorphonuclear leukocytes (PMNs) and, thus, participates in tissue injury by
      recruiting PMNs in a pathophysiologic scenario of periodontal diseases. The aim
      of the present study was to assess the relationship between clinical parameters
      and concentrations of LTB(4) within gingival crevicular fluid (GCF) from inflamed
      gingiva and periodontitis sites before and after the treatment of periodontitis.
      METHODS: Sixty subjects were divided into three groups with 20 subjects in each
      group: healthy (group 1), gingivitis (group 2), and chronic periodontitis (group
      3). Groups were based on periodontal disease index (PDI), clinical attachment
      loss (CAL), and radiographic evidence of bone loss. Group 4 consisted of the
      subjects in group 3 at 6 to 8 weeks after treatment, i.e., scaling and root
      planing (SRP). GCF samples collected from each patient were quantified for LTB(4)
      using an enzymatic immunometric assay. In addition, the correlation between in
      situ LTB(4) levels and clinical parameters was analyzed in each group. RESULTS:
      The highest mean LTB(4) concentration in GCF was observed in group 3 (185.2
      pg/microl), and the lowest was observed in group 1 (39.6 pg/microl). Its level in
      group 3 decreased to 79.35 pg/microl after treatment (group 4). Further, GCF
      LTB(4) levels in all groups showed a statistically significant positive
      correlation with PDI and CAL (P <0.005). CONCLUSION: The substantial increase in
      GCF LTB(4) concentrations with the severity of periodontal disease and a
      concomitant decrease in its level following SRP in subjects with periodontitis
      suggest a possible role for LTB(4) in the progression of periodontal disease.

PMID- 18052706
TI  - Subgingival microbiologic effects of one-time irradiation by CO2 laser: a pilot
      study.
AB  - BACKGROUND: Third-generation carbon dioxide (3-CO(2)) lasers have handpieces that
      accommodate a periodontal insert that permits irradiation directly into the
      periodontal pocket/sulcus. The purpose of this pilot study was to evaluate, by
      scanning electron microscopy (SEM), the surface effects of 3-CO(2) laser
      treatment on the root surfaces and soft tissues and to investigate the effects of
      3-CO(2) laser on periodontal pathogenic bacteria compared to negative controls.
      METHODS: Five patients with chronic periodontitis and treatment planned for a
      maxillary immediate denture were included in the study. Periodontal pockets with
      a mean probing depth of 5.5 +/- 0.8 mm were irradiated one time by CO(2) laser
      (wavelength of 10,600 nm) at a power of 2.2 W, 50 Hz, an 80-millisecond pulse
      length, and an exposure rate of 1 mm per 5 seconds. DNA analysis of eight
      periodontal bacteria was performed on samples collected from laser-treated and
      control sites prior to and immediately following treatment and was compared
      between groups. In addition, block biopsies, including soft tissue, were
      harvested for SEM examination. RESULTS: SEM examination of test group specimens
      showed heat damage on the soft tissues in three of 17 specimens (17.6%). In
      addition, 11.7% (two of 17) of the 3-CO(2)-treated teeth exhibited localized
      slight damage to root surfaces. Microbiologic results of the control sites
      indicated that 90.6% of the bacterial counts remained the same, 6% increased, and
      3% decreased. In the test group, 71.25% of the bacterial count analyses for the
      eight different periodontal microbes remained the same, 12.50% increased, and
      16.25% decreased. CONCLUSION: A one-time use of the 3-CO(2) laser in periodontal
      pockets did not sterilize or substantially reduce subgingival bacterial
      populations compared to negative controls.

PMID- 18052707
TI  - Matrix metalloproteinase-2, -9, and -12 gene polymorphisms in generalized
      aggressive periodontitis.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are involved in periodontal tissue
      remodeling and degradation. Polymorphisms in the promoter region of the MMP-2 and
      -9 genes and in the coding region of the MMP-12 gene could affect transcription
      and the function of these enzymes. The aim of the present study was to determine
      the association between the aforementioned MMP polymorphisms and generalized
      aggressive periodontitis (GAgP). METHODS: Genomic DNA was obtained from the
      peripheral blood of 92 subjects with GAgP and 157 periodontally healthy subjects.
      MMP-2 -735C/T, MMP-9 -1562C/T, and MMP-12 357Asn/Ser polymorphisms were genotyped
      by polymerase chain reaction and restriction fragment length polymorphism.
      Probing depth, clinical attachment loss, supragingival plaque accumulation, and
      bleeding on probing were recorded. The data were analyzed by chi(2), logistic
      regression, and Mann-Whitney U tests. RESULTS: The genotype distributions, allele
      frequencies, and rare allele carriage of MMP-2 and MMP-12 genes were similar in
      GAgP and healthy subjects (P >0.05). T allele frequency and T allele carriage of
      the MMP-9 -1562 C/T polymorphism were significantly lower in the GAgP group than
      in the healthy group (P <0.05). In addition, logistic regression analysis
      revealed a protective effect for MMP-9 -1562 T allele carriers (odds ratio =
      0.52; P = 0.04). CONCLUSIONS: MMP-2 -735C/T and MMP-12 357Asn/Ser polymorphisms
      are not related to GAgP. Conversely, the MMP-9 -1562 gene T allele might be
      associated with a decreased risk for GAgP in the Turkish population.

PMID- 18052708
TI  - A patient-centered clinical evaluation of acellular dermal matrix graft in the
      treatment of gingival recession defects.
AB  - BACKGROUND: The present randomized controlled trial was conducted to evaluate
      acellular dermal matrix (ADM) graft in terms of patient satisfaction and its
      effectiveness and efficiency in the treatment of gingival recession. METHODS:
      Fourteen patients (seven males and seven females) with Miller Class I and II
      recessions > or =3 mm participated in this 6-month clinical study. They were
      assigned randomly to the ADM group (ADM graft and coronally positioned flap
      [CPF]) or the CPF group (CPF alone). Results were evaluated based on parameters
      measuring patient satisfaction and clinical outcomes associated with the two
      treatment procedures. Significance was set at P <0.05. RESULTS: The mean
      recession was 4.0 +/- 1.0 mm and 3.7 +/- 0.7 mm for the ADM and CPF groups,
      respectively. For the ADM group, the defect coverage was 3.85 +/- 0.89 mm or
      97.14% compared to the CPF group, in which the defect coverage was 2.85 +/- 0.89
      mm or 77.42%. The difference between the two groups was statistically significant
      (P <0.05). There were no statistically significant differences between the two
      groups in the remaining clinical parameters and overall patient satisfaction
      except in criteria related to patient comfort and cost effectiveness, in which
      CPF alone produced significantly better results (P <0.03). CONCLUSIONS: ADM graft
      is significantly superior with regard to effectiveness and efficiency in the
      treatment of gingival recession than CPF alone. CPF emerges as a better option
      than ADM graft in terms of cost effectiveness and patient comfort.

PMID- 18052709
TI  - CCL28 effects on periodontal pathogens.
AB  - BACKGROUND: Chemokines are small proteins that signal to and attract cells of the
      immune system; they are vital components in the modulation of immunity and wound
      healing. A newly described chemokine was reported to have antibacterial and
      antifungal activity. This chemokine, chemokine (C-C motif) ligand 28 (CCL28; also
      called mucosae-associated epithelial chemokine), is secreted by mucosal
      epithelial cells and is found in saliva and in breast milk. The objective of this
      study was to test whether CCL28 has antibacterial activity against two anaerobic
      periodontal pathogens: Porphyromonas gingivalis and Actinobacillus
      actinomycetemcomitans. METHODS: We used a bacterial viability test, in which two
      fluorescent dyes are bound differentially to living and killed bacteria. We
      tested the bacteria at concentrations of 2 x 10(7)/ml, exposing them to CCL28 at
      concentrations from 0.04 to 10 microM. RESULTS: CCL28 was effective at killing
      both organisms. After 1 hour of exposure to the chemokine under appropriate
      oxygen conditions, the percentage of living organisms was reduced significantly
      for each species. We estimated the 50% effective concentration to be
      approximately 0.7 microM for P. gingivalis and approximately 2.0 microM for A.
      actinomycetemcomitans (N = five experiments each). We confirmed these
      observations using standard bacterial plating methods. CONCLUSION: Because this
      chemokine is secreted into the saliva, a reduction in salivary flow (as in
      xerostomia) may diminish the oral self-defense mechanisms by also reducing the
      exposure of bacteria to the antibacterial action of CCL28.

PMID- 18052710
TI  - Apoptosis and expression of caspase-3 in cyclosporin-induced gingival overgrowth.
AB  - BACKGROUND: The pathogenesis of epithelial thickening in gingival overgrowth
      remains obscure. Apoptosis plays an important role in maintaining tissue
      hemostasis. The aim of the present study was to investigate apoptosis via
      immunohistochemical analyses in cyclosporin A-induced gingival overgrowth tissue
      samples to determine whether these processes play a role in the pathogenesis of
      gingival overgrowth. METHODS: Gingival biopsies (one per person) were harvested
      from 22 renal transplant recipients (eight men and 14 women; mean age, 36.4 +/-
      13.3 years) who had been diagnosed with cyclosporin A-induced gingival
      enlargement and from 12 systemically healthy persons (seven men and five women;
      mean age, 27.0 +/- 16.0 years) with plaque-induced gingivitis. Distributions of
      caspase-3 and apoptosis were determined immunologically. RESULTS: Significant
      differences were found with regard to caspase-3 levels and the extent of
      apoptosis between the cyclosporin A group and the control group. Plaque index,
      gingival index, and probing depths were significantly lower in the control group.
      CONCLUSION: The extent of keratinocyte apoptosis and decreased levels of caspase
      3 may be an important factor affecting the gingiva of kidney transplant
      recipients with cyclosporin A-induced gingival overgrowth.

PMID- 18052711
TI  - Enamel matrix derivative induces connective tissue growth factor expression in
      human osteoblastic cells.
AB  - BACKGROUND: Enamel matrix derivative (EMD) stimulates the production of
      transforming growth factor-beta (TGF-beta), which has been suggested to play a
      role in mediating the effects of EMD in periodontal tissue regeneration.
      Connective tissue growth factor (CTGF) is a mediator of TGF-beta and promotes
      cell development. The interaction between EMD and CTGF is unknown. This study
      explored the effects of EMD on CTGF expression in human osteoblastic cells and
      whether the interaction is modulated by the TGF-beta signaling pathway. Also, the
      roles of CTGF in cell proliferation, cell cycle progression, and mineralized
      nodule formation of EMD-induced osteoblastic cultures were examined. METHODS:
      Human osteoblastic cells (Saos-2) were treated with 25 to 100 microg/ml EMD with
      or without the addition of TGF-beta inhibitor. CTGF mRNA expression was detected
      by reverse transcription-polymerase chain reaction (RT-PCR), and CTGF protein
      levels were assayed by Western blot analysis. In addition, cell cycle progression
      and DNA synthesis were determined by flow cytometry and 5-bromo-2'-deoxyuridine
      (BrdU) incorporation following EMD treatment with or without CTGF antibody.
      Mineralization was examined by alizarin red staining and quantified by elution
      with cetylpyridinium chloride. RESULTS: Western blot and RT-PCR analysis
      demonstrated a dose-dependent increase of CTGF expression by EMD. EMD-induced
      CTGF expression was reduced significantly in the presence of TGF-beta inhibitor.
      Cell cycle and BrdU analysis revealed an increase in cell proliferation following
      EMD treatment, which was due to an increase in the percentage of cells in the
      G2/M phase of the cell cycle. No significant effect was found when anti-CTGF
      antibody was added. Conversely, mineralization was inhibited significantly in EMD
      treated cultures in the presence of anti-CTGF antibody. CONCLUSIONS: EMD
      stimulates CTGF expression, and the interaction is modulated via TGF-beta in
      osteoblastic cells. Also, CTGF affects EMD-induced osteoblastic mineralization
      but not cell proliferation. To our knowledge, these results provide novel insight
      into EMD-CTGF interaction, two biomodifiers that have therapeutic relevance to
      tissue engineering and regeneration.

PMID- 18052712
TI  - Sudden improvement of insulin sensitivity related to an endodontic treatment.
AB  - BACKGROUND: Inflammation contributes to the pathogenesis of diabetes. A
      reciprocal relationship exists between diabetes and chronic periodontitis. This
      report describes the effects of an acute focal dental inflammation and subsequent
      endodontic treatment on the required insulin dosage of a 70-year-old man who had
      moderately controlled diabetes. METHODS: Following an exacerbation of a combined
      endodontic-periodontic (endo-perio) lesion of tooth #3, the patient noticed a
      sudden increase in his insulin demand. After 3 weeks, the required dosage was
      approximately 100% greater. In association with hyperglycemic incidents, he
      reported a prickling sensation in this tooth. The radiograph showed circular bone
      loss around the tooth. RESULTS: Just 1 day after the root-canal preparation, the
      insulin need decreased to approximately 50% of that required prior to treatment.
      Subsequently, an incision and systemic antibiotics were necessary because of the
      formation of a periodontal abscess. The insulin demand remained low despite this
      complication. Forty days after endodontic treatment, the insulin dosage was at a
      level comparable to that taken 4 weeks before the root-canal preparation.
      CONCLUSIONS: This clinical case revealed a highly relevant correlation between
      insulin resistance and a local dental inflammation. To avoid an increase in
      insulin resistance, it seems important to attend to radically non-vital teeth as
      well as any other dental inflammation in diabetic patients.

PMID- 18052713
TI  - Treatment of a large periradicular lesion of endodontic origin around a dental
      implant with enamel matrix protein derivative.
AB  - BACKGROUND: This case report describes the healing of a large periradicular
      lesion involving an adjacent implant. Endodontic surgery was performed in
      combination with placement of an enamel matrix protein derivative. METHODS:
      Endodontic surgery was performed, including root end resection at a 90 degrees
      angle. Ultrasonic tips were used for retrograde preparation, and the retrograde
      cavity was sealed with zinc oxide-eugenol. The area was filled carefully with
      enamel matrix proteins. Sutures were removed after a 2-week healing period.
      RESULTS: There were no symptoms of pain, inflammation, or discomfort at 18 months
      post-surgery. Radiographs showed complete healing of the periradicular lesion.
      CONCLUSIONS: Combining an enamel matrix protein derivative with conventional
      surgery may improve the clinical outcome of large endodontic lesions. Additional
      research is warranted.

PMID- 18052714
TI  - Er:YAG laser osteotomy for intraoral bone grafting procedures: a case series with
      a fiber-optic delivery system.
AB  - BACKGROUND: With a wavelength of 2.94 mum, the erbium-doped:yttrium, aluminum,
      and garnet (Er:YAG) laser is suitable for cutting vital osseous tissue. To
      analyze the benefit of laser osteotomy in implant dentistry, a fiber-guided
      Er:YAG laser was used for harvesting intraoral bone grafts. METHODS: In 10
      consecutive patients (six males and four females), 12 block grafts were obtained
      from the ramus (nine cases), chin (two cases), and tuberosity (one case) region.
      For the osteotomies, the laser settings included a pulse energy of 500 mJ, a
      pulse duration of 250 microseconds, and a pulse frequency of 12 Hz. During
      osteotomy, the laser fiber tip was kept 1 to 2 mm away from the bone surface.
      RESULTS: Cut efficiency was satisfactory with almost no constraint on the
      positioning of the laser tip. Laser osteotomy was precise and allowed the blocks
      to be prepared with minimal waste of bone. The risk for accidentally injuring
      adjacent soft tissues was minimal. The postoperative wound-healing process was
      not impaired, and there were no signs of carbonization; however, the surgical
      procedures were time consuming. CONCLUSIONS: Using the Er:YAG laser with the
      aforementioned settings, successful laser osteotomy was achieved without any
      complications. However, because laser osteotomy was time-intensive and offered no
      depth control, it demonstrated only slight advantages for intraoral bone-grafting
      procedures. If the ablation process could be accelerated, the Er:YAG laser would
      be a promising alternative to conventional instruments for this surgical
      technique.

PMID- 18052716
TI  - Detection of Rickettsia amblyommii in association with a tick bite rash.
AB  - In the summer of 2006, an Amblyomma americanum tick was removed from a woman in
      central North Carolina, who subsequently developed a rash at the site of tick
      attachment. When examined by polymerase chain reaction (PCR) for Borrelia,
      Anaplasma, Ehrlichia, Babesia, Rickettsia, and Bartonella DNA, only the
      Rickettsia primers generated an amplicon, which was identified as "R. amblyommii"
      by sequencing. To our knowledge, this is the first case in which R. amblyommii
      was temporally associated with a rash.

PMID- 18052717
TI  - Do mitochondriotropic antioxidants prevent chlorinative stress-induced
      mitochondrial and cellular injury?
AB  - Reactive chlorine species such as hypochlorous acid (HOCl) are cytotoxic oxidants
      generated by activated neutrophils at the sites of chronic inflammation. Since
      mitochondria are key mediators of apoptosis and necrosis, we hypothesized that
      mitochondriotropic antioxidants could limit HOCl-mediated intracellular oxidative
      injury to human fetal liver cells, preserve mitochondrial function, and prevent
      cell death. In this current study, we show that recently developed mitochondria
      targeted antioxidants (MitoQ and SS31) significantly protected against HOCl
      induced mitochondrial damage and cell death at concentrations >or=25 nM. Our
      study highlights the potential application of mitochondria-specific targeted
      antioxidants for the prevention of cellular dysfunction and cell death under
      conditions of chlorinative stress, as occurs during chronic inflammation.

PMID- 18052718
TI  - Mitochondria as a target for the cardioprotective effects of nitric oxide in
      ischemia-reperfusion injury.
AB  - During cardiac ischemia-reperfusion (IR) injury, excessive generation of reactive
      oxygen species (ROS) and overload of Ca(2+) at the mitochondrial level both lead
      to opening of the mitochondrial permeability transition (PT) pore on reperfusion.
      This can result in the depletion of ATP, irreversible oxidation of proteins,
      lipids, and DNA within the cardiomyocyte, and can trigger cell-death pathways. In
      contrast, mitochondria are also implicated in the cardioprotective signaling
      processes of ischemic preconditioning (IPC), to prevent IR-related pathology.
      Nitric oxide (NO*) has emerged as a potent effector molecule for a variety of
      cardioprotective strategies, including IPC. Whereas NO* is most noted for its
      activation of the "classic" soluble guanylate cyclase (sGC) signaling pathway,
      emerging evidence indicates that NO can directly act on mitochondria, independent
      of the sGC pathway, affording acute cardioprotection against IR injury. These
      direct effects of NO* on mitochondria are the focus of this review.

PMID- 18052719
TI  - Multifactorial optimization of gammaretroviral gene transfer into human T
      lymphocytes for clinical application.
AB  - The ability to genetically modify human T cells to target tumor antigens through
      retroviral gene transfer constitutes a potentially powerful approach to cancer
      immunotherapy. However, low transduction efficiencies may hamper the efficacy of
      such therapeutic strategies in the clinical setting. Most commonly,
      gammaretroviral gene transfer into T cells is conducted through spinoculation,
      that is, centrifugation of retroviral particles and T cells on RetroNectin-coated
      non-tissue culture vessels. Here we present data investigating the impact of
      temperature, speed, and frequency of spinoculation on T cell transduction
      efficiencies. We found that all three variables independently impacted gene
      transfer, with increasing temperature, speed, and frequency of spinoculation all
      enhancing the transduction of T cells. These improved conditions were additive,
      with the greatest proportion of transduced T cells being generated at the highest
      tested temperature and speed, after daily spinoculation for 2 to 3 days. Under
      these conditions, enhanced gene transfer was observed in T cells derived from
      healthy donors, using research-grade vector stocks. Whereas both RetroNectin and
      spinoculation were critical to optimal gene transduction, preloading of
      gammaretroviral particles before spinoculation did not enhance gene transfer.
      Significantly, application of these enhanced transduction conditions to T cells
      derived from previously treated patients with chronic lymphocytic leukemia
      allowed for adequate gene transfer under both small-scale and large-scale
      clinically applicable conditions using either preclinical or current Good
      Manufacturing Practice-grade gammaretroviral vector stocks.

PMID- 18052720
TI  - Enhanced gene expression conferred by stepwise modification of a nonprimate
      lentiviral vector.
AB  - The practical application of gene transfer as a treatment for genetic diseases
      such as cystic fibrosis or hemophilia has been hindered, in part, by low
      efficiencies of vector delivery and transgene expression. We demonstrated that a
      feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the
      envelope glycoprotein from the baculovirus Autographa californica (GP64)
      efficiently transduces and persistently expresses a reporter gene in respiratory
      epithelium in the absence of agents that disrupt cellular tight junction
      integrity. GP64-pseudotyped FIV also efficiently transduced murine hepatocytes
      after tail vein delivery. To improve the FIV-based vector, we tested the
      contribution of a series of modifications to luciferase expression in vitro and
      in vivo. These modifications included the addition of spleen necrosis virus U5
      (SNV U5) and mutation of the major splice donor and gag start codon located in
      the packaging region of the FIV transgene plasmid. After vector modification, we
      observed significantly enhanced expression of luciferase in respiratory epithelia
      after nasal application and in the liver after tail vein delivery. In addition,
      we observed significantly enhanced human factor VIII production after tail vein
      delivery. These sequential modifications provide an improved FIV lentivirus
      platform for gene therapy applications and may be applied to other retroviral
      vectors.

PMID- 18052721
TI  - Type II pneumocyte-restricted green fluorescent protein expression after
      lentiviral transduction of lung epithelial cells.
AB  - Type II alveolar epithelial (AT2) cell-specific reporter expression has been
      highly useful in the study of embryology and alveolar regeneration in transgenic
      mice. Technologies enabling efficient gene transfer and cell type-restricted
      transgene expression in AT2 cells would allow for correction of AT2 cell-based
      diseases such as genetic surfactant deficiencies. Moreover, such approaches are
      urgently required to investigate differentiation of AT2 cells from adult and
      embryonic stem cells of other species than mouse. Using a human surfactant
      protein C (SP-C) promoter fragment, we have constructed lentiviral vectors
      enabling AT2-restricted transgene expression and identification of stem cell
      derived AT2 cells. Lung epithelial cell lines M3E3/C3, H441, RLE-6TN, A549, MLE
      12, and MLE-15 were characterized at the molecular and ultrastructural levels to
      identify cell lines useful to assess the cell type specificity of our vector
      constructs. After transduction, no green fluorescent protein (GFP) expression was
      observed in nontarget cells including bronchial H441 cells, pulmonary A549 cells,
      fibroblasts, smooth muscle cells, and endothelial cells. In contrast, and in
      correlation with endogenous SP-C expression, lentiviral transduction resulted in
      stable GFP expression in MLE-12 and MLE-15 AT2 cells. In conclusion, we have
      constructed a lentiviral vector mediating SP-C promoter-dependent GFP expression.
      Transgene expression strictly corresponds with an AT2 phenotype of the transduced
      cells. In particular, the generated vector should facilitate local alveolar gene
      therapy and investigation of alveolar regeneration and stem cell differentiation.

PMID- 18052722
TI  - Neonatal intraperitoneal or intravenous injections of recombinant adeno
      associated virus type 8 transduce dorsal root ganglia and lower motor neurons.
AB  - Targeting lower motor neurons (LMNs) for gene delivery could be useful for
      disorders such as spinal muscular atrophy and amyotrophic lateral sclerosis. LMNs
      reside in the ventral gray matter of the spinal cord and send axonal projections
      to innervate skeletal muscle. Studies have used intramuscular injections of adeno
      associated virus type 2 (AAV2) to deliver viral vectors to LMNs via retrograde
      transport. However, treating large areas of the spinal cord in a human would
      require numerous intramuscular injections, thereby increasing viral titer and
      risk of immune response. New AAV serotypes, such as AAV8, have a dispersed
      transduction pattern after intravenous or intraperitoneal injection in neonatal
      mice, and may transduce LMNs by retrograde transport or through entry into the
      nervous system. To test LMN transduction after systemic injection, we
      administered recombinant AAV8 (rAAV8) carrying the green fluorescent protein
      (GFP) gene by intravenous or intraperitoneal injection to neonatal mice on
      postnatal day 1. Tissues were harvested 5 and 14 days postinjection and analyzed
      by real-time polymerase chain reaction and GFP immunohistochemistry to assess the
      presence of AAV genomes and GFP expression, respectively. Spinal cords were
      positive for AAV genomes at both time points. GFP immunohistochemistry revealed
      infrequent labeling of LMNs across all time points and injection routes. Somewhat
      surprisingly, there was extensive labeling of fibers in the dorsal horns and
      columns, indicating dorsal root ganglion transduction across all time points and
      injection routes. Our data suggest that systemic injection of rAAV8 is not an
      effective delivery route to target lower motor neurons, but could be useful for
      targeting sensory pathways in chronic pain.

PMID- 18052723
TI  - Tumor necrosis factor (TNF) is a potent rat mast cell chemoattractant.
AB  - It is well known that mast cell number increases in local tissues under different
      pathophysiologic conditions, although the humoral factors that stimulate local
      mast cell accumulation within tissues are not yet well known. Taking into account
      that tumor necrosis factor (TNF) influences tissue mast cell activity in various
      ways, the aim of the present study was to investigate the chemotactic activity of
      TNF for rat peritoneal mast cells. We have found that TNF induces mast cell
      migratory response in a dose-dependent manner, even in the absence of
      extracellular matrix (ECM) proteins. Significant migration was observed at
      concentrations of TNF as low as approximately 3 fM; higher TNF concentrations
      caused significant inhibition of spontaneous mast cell migration. In the presence
      of ECM proteins, TNF induced migration of mast cells in a biphasic manner, with
      peaks of migration occurring at approximately 0.3 fM and approximately 60 pM (in
      the presence of fibronectin) and at approximately 0.6 fM and approximately 600 pM
      (in the presence of laminin). Under the same experimental conditions, RANTES
      induced dose-dependent mast cell migration, and the optimal concentration of this
      chemokine for maximal migration was approximately 13 nM. The mast cell migratory
      response to lower concentrations of TNF was chemotactic and to higher TNF
      concentrations was due to chemokinesis. TNF-induced mast cell migration was
      completely blocked by neutralizing anti-TNF and anti-TNFR1 antibodies. The
      tyrosine kinase inhibitor, genistein, significantly abrogated mast cell migration
      toward TNF. Additionally, we have documented that TNF does not induce
      degranulation of rat mast cells. Taken together, our results indicate that TNF
      serves as an extremely potent chemotactic factor for rat mast cells that would
      cause accumulation of these cells at the site of diverse pathophysiologic
      conditions accompanied by inflammation.

PMID- 18052724
TI  - Expression of chemokine receptor CCR4 and its ligands (CCL17 and CCL22) in murine
      contact hypersensitivity.
AB  - Chemokine receptor CCR4 and its ligands (CCL17 and CCL22) are important for the
      recruitment of memory T cells into the skin in various cutaneous immune diseases.
      However, information on CCR4 and its ligands in contact hypersensitivity is
      relatively limited. In this study, we investigated the expression of CCR4, CCL17,
      and CCL22 in a mouse model of contact hypersensitivity to oxazolone. Contact
      sensitization to oxazolone increased the proportions of memory CD4+ T cells in
      the draining lymph nodes, spleen, and peripheral blood. Although CCR4+ mRNA and
      CCR4+ cells were detectable in naive mouse lymph nodes, they significantly
      increased in the sensitized mice. The majority of CCR4+ cells in both control and
      sensitized mouse lymph nodes were CD4+ T cells. In the skin of naive mice, the
      mRNAs for CCR4, CCL17, and CCL22 were detectable, but only CCL17 and CCL22
      proteins were constitutively expressed in the skin, particularly in the
      epidermis. Interestingly, the mRNAs for CCR4 and its two ligands were
      significantly elevated in the inflamed skin of mice with contact hypersensitivity
      to oxazolone. Furthermore, a subpopulation of cells that infiltrated the skin was
      CCR4+ cells. Finally, the expression of CCL17 and CCL22 proteins was
      significantly enhanced in the epidermis of inflamed skin. Thus, our study
      provides direct evidence for the presence of CCR4 and its ligands in mouse
      contact hypersensitivity.

PMID- 18052725
TI  - Improvement in postburn hypertrophic scar after treatment with IFN-alpha2b is
      associated with decreased fibrocytes.
AB  - Hypertrophic scar (HTS) following thermal injury is a dermal fibroproliferative
      disorder that leads to considerable morbidity. Previous clinical studies from our
      laboratory have suggested that interferon-alpha2b (IFN-alpha2b) improves scar
      quality as a result of suppression of fibroblast functions. Fibrocytes, which
      constitute a unique cell population, have recently been reported to contribute to
      wound healing and to a variety of fibrotic conditions, including HTS. Therefore,
      we hypothesize that improvement of scar in HTS patients after IFN-alpha2b
      treatment may be associated with a decreased number of fibrocytes or altered
      fibrocyte function. Using flow cytometry, immunofluorescent staining, and
      confocal microscopy, we demonstrate here that the marker protein leukocyte
      specific protein 1 (LSP1) is stably expressed by fibrocytes for at least 2
      months, whereas other potential fibrocyte markers, such as CD34 and CD45,
      gradually disappear. Using dual staining immunohistochemistry for LSP1 and
      procollagen, we demonstrated a significant reduction in numbers of fibrocytes in
      HTS tissue from patients after treatment with systemic IFN-alpha2b. IFN-alpha2b
      was shown to abolish fibrocyte differentiation from peripheral blood mononuclear
      cells (PBMCs) in vitro in a dose-dependent fashion. In addition, IFN-alpha2b
      inhibits proliferation of fibrocytes and T lymphocytes and reduces transforming
      growth factor-beta (TGF-beta)-mediated alpha-smooth muscle actin (alpha-SMA)
      expression in fibrocytes. Taken together with our previous study in which we
      showed that fibrocytes could indirectly regulate dermal fibroblasts in burn
      patients, the present study suggests that the improvement of scar quality in HTS
      patients after IFN-alpha2b treatment is associated with decreased numbers and
      activities of fibrocytes.

PMID- 18052726
TI  - The existence of gender difference in IL-1Ra gene polymorphism.
AB  - Interleukin-1beta (IL-1beta) and its endogenous antagonist IL-1 receptor
      antagonist (IL-1ra) play an important role in various inflammatory responses. The
      production of IL-1 and IL-1ra is regulated by genotypic and nongenotypic factors
      and is different between men and women. The aim of this study was to examine the
      existence of gender difference in the genetic polymorphism of these two
      cytokines. The genotypes of IL-1beta-511 biallelic polymorphism and that of IL
      1Ra (IL-1RN) penta-allelic polymorphism were determined in 319 healthy Jewish
      subjects, 156 female and 163 male, using PCR amplification. The results showed
      that there was a gender difference in IL-1Ra gene polymorphism expressed by a
      higher incidence of IL1RN*1/IL1RN*1 homozygotes and a lower occurrence of
      IL1RN*1/IL1RN*2 heterozygotes in men compared with women. Furthermore, allele
      IL1RN*1 was more frequent in men, whereas allele IL1RN*2 was more prevalent in
      women. There was no difference in IL-1beta gene polymorphism between the two
      genders. It is conceivable that the gender difference in IL-1Ra gene polymorphism
      found in the current study may affect IL-1 and IL-1ra levels. This diversity
      might be one of the causes for the sex differences in immune response observed in
      various conditions, such as autoimmune diseases, pain perception, and premature
      delivery.

PMID- 18052728
TI  - IFN-gamma enhances immune responses to E. coli infection in the chicken.
AB  - Escherichia coli infection of the respiratory system in chickens occurs as a
      sequel to a variety of environmental stressors or microbial infections,
      culminating as chronic respiratory disease (CRD) syndrome or colibacillosis.
      These diseases cause significant production losses in poultry. With the growing
      concerns about the use of antibiotics in animal production, for diseases such as
      CRD, alternative natural agents, like cytokines, may be considered for enhancing
      health by stimulating the immune system. The current study was aimed at
      understanding the in vivo effects of recombinant chicken interferon-gamma (ChIFN
      gamma) treatment on a variety of immunologic parameters during E. coli infection
      in chickens. Administration of ChIFN-gamma to chickens increased the percentage
      of phagocytes in lung and blood of E. coli-infected birds. At the phenotypic
      level, there was an increase in the percentage of cells expressing MHC II in the
      air sac, with a concomitant reduction in the proportion of these cells in blood.
      Furthermore, the blood plasma from ChIFN-gamma-treated infected birds showed an
      increased level of interleukin-6 (IL-6) activity. Cumulatively, these findings
      are indicative of in vivo enhancement of immune responses due to ChIFN-gamma.
      However, administration of ChIFN-gamma protein did not mitigate the development
      of air sac lesions following E. coli infection.

PMID- 18052730
TI  - Research examines contaminants in food, deaths of pets.

PMID- 18052729
TI  - Cross-inhibition of interferon-induced signals by GM-CSF through a block in Stat1
      activation.
AB  - We investigated the effects of granulocyte-macrophage colony-stimulating factor
      (GM-CSF) on biologic signals induced by interferon-alpha (IFN-alpha) and IFN
      gamma. In hematopoietic cell lines, IFN-induced signaling was investigated by
      Western blotting, electrophoretic mobility shift assays (EMSA), flow cytometry,
      protein-tyrosine phosphatase (PTP) assays, and RT-PCR. GM-CSF inhibited IFN-alpha
      induced and IFN-gamma-induced Stat1 tyrosine phosphorylation in a time-dependent
      manner. EMSA showed that GM-CSF inhibited IFN-alpha-induced and IFN-gamma-induced
      IFN-gamma activator sequence (GAS) binding activity. As a consequence, IFN
      induced transcription of the early response gene, IFN-stimulated gene 54 (ISG54),
      was inhibited. The expression of IFN regulatory factor-1 (IRF-1) and MHC class I
      antigens was downregulated at protein levels in hematopoietic cell lines (U937,
      THP1). In contrast to GM-CSF, granulocyte colony-stimulating factor (G-CSF) and
      interleukin-3 (IL-3) did not influence the IFN-induced Stat1 activation. To
      explore the molecular mechanism of suppression of Stat1 tyrosine phosphorylation,
      we investigated the induction and activation of cytokine-inducible SH2-containing
      protein/suppressor of cytokine signaling (CIS/SOCS) molecules and phosphatases on
      GM-CSF treatment. In contrast to G-CSF and IL-3, GM-CSF strongly induced the
      expression of CIS1 and SOCS2 at mRNA levels, but overexpression of CIS1 or SOCS2
      in HEK293 cells did not show inhibition of Stat1 tyrosine phosphorylation upon
      IFN treatment. In PTP assays, on GM-CSF incubation, no enhanced src homology 2
      domain tyrosine phosphatase 1 and 2 (SHP1 and SHP2) activity was detectable.
      However, GM-CSF-induced downregulation of Tyk2 and Jak1 tyrosine phosphorylation
      as well as Tyk2 protein levels likely contributed to the reduced Stat1 tyrosine
      phosphorylation. In hematopoietic cells, GM-CSF antagonizes IFN-induced signals
      by a block in Stat1 activation.

PMID- 18052731
TI  - Assessment of three automated assays for C-reactive protein determination in
      dogs.
AB  - OBJECTIVE: To determine the characteristics of an automated canine C-reactive
      protein (CRP) assay and evaluate 2 human CRP assays for use in dogs. Animals-56
      client-owned dogs with pyometra and 11 healthy control dogs. PROCEDURES: Samples
      from 11 dogs with high (> 100 mg/L) or low (< 10 mg/L) CRP concentrations
      (determined by use of a canine ELISA) were evaluated by use of the automated
      canine CRP assay. Intra- and interassay imprecision was determined (by use of
      those 2 plasma pools), and assay inaccuracy was assessed by use of logistic
      regression analysis of results obtained via ELISA and the automated canine CRP
      assay. Two automated human CRP assays were used to measure plasma CRP
      concentration in 10 dogs. RESULTS: By use of the ELISA, mean +/- SD plasma CRP
      concentration was 96.1 +/- 38.5 mg/L and 10.1 +/- 23.2 mg/L in dogs with pyometra
      and control dogs, respectively. The automated canine assay had intra-assay
      coefficients of variation (CVs) of 7.8% and 7.9%, respectively, and interassay
      CVs of 11.1% and 13.1%, respectively. Results from the automated assay were
      highly correlated with results obtained via ELISA. The human assay results did
      not exceed 0.4 mg/L in any dog. CONCLUSIONS AND CLINICAL RELEVANCE: The automated
      canine CRP assay had less interassay imprecision, compared with the ELISA. The 2
      human CRP assays were not suitable for analysis of canine plasma samples. The
      automated canine CRP assay was more precise than the ELISA for serial evaluations
      of plasma CRP concentration in dogs.

PMID- 18052732
TI  - Cardiopulmonary effects of administration of a combination solution of xylazine,
      guaifenesin, and ketamine or inhaled isoflurane in mechanically ventilated
      calves.
AB  - OBJECTIVE: To compare the cardiopulmonary effects of administration of a solution
      of xylazine, guaifenesin, and ketamine (XGK) or inhaled isoflurane in
      mechanically ventilated calves undergoing surgery. ANIMALS: 13 male calves 2 to
      26 days of age. Procedures-In calves in the XGK group, anesthesia was induced
      (0.5 mL/kg) and maintained (2.5 mL/kg/h) with a combination solution of xylazine
      (0.1 mg/mL), guaifenesin (50 mg/mL), and ketamine (1.0 mg/mL). For calves in the
      isoflurane group, anesthesia was induced and maintained with isoflurane in
      oxygen. The rates of XGK infusion and isoflurane administration were adjusted to
      achieve suitable anesthetic depth. All calves received 100% oxygen and were
      mechanically ventilated to maintain end-tidal carbon dioxide concentrations from
      35 to 40 mm Hg and underwent laparoscopic bladder surgery through an abdominal
      approach. Cardiopulmonary variables were measured before induction and at
      intervals up to 90 minutes after anesthetic induction. RESULTS: The quality of
      induction was excellent in all calves. The XGK requirements were 0.57 +/- 0.18
      mL/kg and 2.70 +/- 0.40 mL/kg/h to induce and maintain anesthesia, respectively.
      Heart rate was significantly lower than baseline throughout the anesthetic period
      in the XGK group. Systolic arterial blood pressure was significantly higher in
      the XGK group, compared with the isoflurane group, from 5 to 90 minutes. Cardiac
      index was lower than baseline in both groups. Differences between groups in
      cardiac index and arterial blood gas values were not significant. CONCLUSIONS AND
      CLINICAL RELEVANCE: Administration of XGK resulted in excellent anesthetic
      induction and maintenance with cardiopulmonary alterations similar to those
      associated with isoflurane in mechanically ventilated calves.

PMID- 18052733
TI  - Effects of perzinfotel on the minimum alveolar concentration of isoflurane in
      dogs.
AB  - OBJECTIVE: To determine the effect of IV administration of perzinfotel on the
      minimum alveolar concentration (MAC) of isoflurane in dogs. Animals-6 healthy
      sexually intact male Beagles. PROCEDURES: Dogs were instrumented with a telemetry
      device that permitted continuous monitoring of heart rate, arterial blood
      pressure, and body temperature. Dogs were anesthetized with propofol (4 to 6
      mg/kg, IV) and isoflurane for 30 minutes before determination of MAC of
      isoflurane. Isoflurane MAC values were determined 4 times, separated by a minimum
      of 7 days, before and after IV administration of perzinfotel (0 [control], 5, 10,
      and 20 mg/kg). Bispectral index and percentage hemoglobin saturation with oxygen
      (SpO(2)) were monitored throughout anesthesia. RESULTS: Isoflurane MAC was 1.32
      +/- 0.14%. Intravenous administration of perzinfotel at 0, 5, 10, and 20 mg/kg
      decreased isoflurane MAC by 0%, 24%, 30%, and 47%, respectively. Perzinfotel
      significantly decreased isoflurane MAC values, compared with baseline and control
      values. The bispectral index typically increased with higher doses of perzinfotel
      and lower isoflurane concentrations, but not significantly. Heart rate, body
      temperature, and SpO(2) did not change, but systolic, mean, and diastolic
      arterial blood pressures significantly increased with decreases in isoflurane MAC
      after administration of perzinfotel at 10 and 20 mg/kg, compared with 0 and 5
      mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of perzinfotel
      decreased isoflurane MAC values. Improved hemodynamics were associated with
      decreases in isoflurane concentration.

PMID- 18052734
TI  - Use of bispectral index to monitor depth of anesthesia in isoflurane-anesthetized
      dogs.
AB  - OBJECTIVE: To evaluate the correlation between the bispectral index (BIS) and end
      tidal isoflurane (ET(ISO)) concentration and compare the use of 3 BIS sensor
      positions in dogs. ANIMALS: 6 adult dogs. PROCEDURES: Mechanically ventilated
      dogs received pancuronium, and depth of anesthesia was altered by increasing
      ET(ISO) concentration from 1.5% to 2.3% and 3.0%. The BIS, suppression ratio
      (relative percentage of isoelectric electroencephalographic waveforms), and
      signal quality index (SQI) were recorded at each ET(ISO) concentration for each
      of 3 BIS sensor positions (frontal-occipital, bifrontal, and frontal-temporal
      positions). RESULTS: The BIS and ET(ISO) concentration were poorly correlated;
      regardless of sensor positioning, mean BIS values did not change significantly as
      ET(ISO) was increased. At 3% isoflurane, regardless of sensor positioning, there
      was an increase in suppression ratio coincident with BIS < 40 in some dogs,
      whereas paradoxic increases in BIS (> 60) were recorded in others. Furthermore,
      at 3.0% isoflurane, the SQI was significantly lower for the bifrontal sensor
      position (compared with values for the other positions), but low SQI values
      prevented recording of BIS values from the frontal-occipital sensor position in 2
      dogs. Overall, BIS values derived from the 3 sensor positions did not differ.
      CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, BIS values may not reflect changes
      in depth of isoflurane anesthesia in the absence of noxious stimulation. Of the 3
      sensor positions, frontal-temporal positioning provided better correlation with
      changes in depth of anesthesia induced via changes in isoflurane concentrations.
      However, the sensor placements yielded similar results at SQI values > 50.

PMID- 18052735
TI  - Evaluation of the influences of exercise, birth date, and osteochondrosis on
      plasma bone marker concentrations in Hanoverian Warmblood foals.
AB  - OBJECTIVE: To determine whether plasma concentrations of bone turnover markers in
      growing Hanoverian foals are influenced by age, housing conditions, or
      osteochondrosis. ANIMALS: 165 healthy foals and 119 foals with osteochondrosis.
      PROCEDURES: Foals were allocated according to birth date and housing management
      into groups of early-born (born before March 31, 2001; n = 154 foals, 88 of which
      were healthy and 66 of which had osteochondrosis) and late-born (born after March
      31, 2001; 130 foals, 77 of which were healthy and 53 of which had
      osteochondrosis) foals. Plasma osteocalcin and carboxyterminal propeptide of type
      I collagen concentrations were analyzed as markers of bone formation, and
      carboxyterminal telopeptide of type I collagen concentration was analyzed as a
      marker of bone resorption. Foals underwent radiographic evaluation to screen for
      osteochondrosis. RESULTS: Plasma concentrations of osteocalcin, carboxyterminal
      propeptide of type I collagen, and carboxyterminal telopeptide of type I collagen
      decreased with age, but these changes were more distinct in late-born foals than
      in early-born foals. Neither sex nor predisposition to develop osteochondrosis
      affected the pattern of bone marker changes in either group. CONCLUSIONS AND
      CLINICAL RELEVANCE: An age-related decrease in concentrations of bone markers was
      seen during the first 200 days of life. Changes in bone marker concentrations
      were similar for foals with osteochondrosis and healthy foals. The correlation
      between the decrease in bone marker concentration and date of birth indicates
      that there are differences in skeletal development between early- and late-born
      foals.

PMID- 18052736
TI  - Intra-articular administration of doxycycline in calves.
AB  - Objective-To evaluate local tissue compatibility of doxycycline hyclate (DOX) in
      antebrachiocarpal joints of calves. Animals-10 healthy calves between 80 and 110
      kg. Procedures-Calves were assigned to 2 treatment groups. Calves in groups
      DOX(low) and DOX(high) were administered 5 and 10 mg of DOX, respectively,
      locally in 1 antebrachiocarpal joint. The contralateral joint served as a control
      joint and was injected with 0.9% NaCl solution. General and local clinical
      findings were scored. Several variables were assessed in blood and synovial fluid
      for 9 days. Calves were euthanatized and pathologic changes and drug residues
      evaluated. Results-Throughout the study, none of the calves had clinical changes
      or abnormal hematologic values. Significant differences between treatment and
      control joints were evident only for matrix metalloproteinases at 0.5 hours after
      injection, with less activity for the DOX-treated joints in both treatment
      groups. Values for all synovial fluid variables, except nitric oxide, increased
      significantly during the first 12 to 72 hours after arthrocentesis in control and
      DOX-treated joints. Histologic examination revealed minimal infiltration of
      inflammatory cells independent of the treatment. No drug residues were detected 9
      days after arthrocentesis in any tissues obtained from the liver, kidneys, fat,
      and skeletal muscles. Conclusions and Clinical Relevance-DOX had excellent intra
      articular compatibility in healthy calves. Arthrocentesis induced a mild
      transient increase of inflammatory mediators in the synovial fluid. Significant
      decreases in matrix metalloproteinase activity in DOX-treated joints may indicate
      a potential chondroprotective effect of DOX.

PMID- 18052737
TI  - Effect of conformation of the distal portion of the femur and proximal portion of
      the tibia on the pathogenesis of cranial cruciate ligament disease in dogs.
AB  - OBJECTIVE: To evaluate mediolateral radiographic views of stifle joints to
      identify conformational differences between athletically sound dogs and dogs with
      cranial cruciate ligament disease (CCLD). SAMPLE POPULATION: Radiographic images
      of 50 stifle joints of 43 dogs with surgically confirmed CCLD and 50 stifle
      joints of 38 dogs without clinical signs of stifle joint disease. PROCEDURES:
      Mediolateral radiographic views of stifle joints were obtained, and long axes of
      the femur, tibia, and femoral condyles were measured. Angles between long axes of
      the femur and femoral condyle and between long axes of the femur and tibia were
      measured. Circles were drawn representing the joint surface of femoral condyles
      (circle 1), area of contact on the tibial plateau (circle 2), and femoral
      trochlea (circle 3). Radii of circles 1, 2 (line F), and 3 were measured.
      Distances between midpoints of circles 1 and 2 (line K) and between midpoint of
      circle 2 and most cranial aspect of the tibial tuberosity (line G) were measured.
      To evaluate differences in conformation that could lead to CCLD, quotients
      derived from measurements were created for comparison; angles were compared
      between dog groups. RESULTS: Significant differences were found in the quotients
      created by the lengths of lines G and F and lines G and K between dogs with and
      without CCLD. CONCLUSIONS AND CLINICAL RELEVANCE: No anatomic differences were
      detected in the distal portion of the femur between dogs with and without CCLD.
      Development of the tibial tuberosity and shape (convexity) of tibial condyles may
      be relevant in the pathogenesis of CCLD.

PMID- 18052738
TI  - Desmosomal gene evaluation in Boxers with arrhythmogenic right ventricular
      cardiomyopathy.
AB  - OBJECTIVE: To sequence the exonic and splice site regions of the 4 desmosomal
      genes associated with the human form of familial arrhythmogenic right ventricular
      cardiomyopathy (ARVC) in Boxers with ARVC and identify a causative mutation.
      ANIMALS: 10 unrelated Boxers with ARVC and 2 unaffected Labrador Retrievers
      (control dogs). PROCEDURES: Exonic and splice site regions of the 4 genes
      encoding the desmosomal proteins plakophilin-2, plakoglobin, desmoplakin, and
      desmoglein-2 were sequenced. Sequences were compared for nucleotide sequence
      changes between affected dogs and the published sequences for clinically normal
      dogs and between affected dogs and the control dogs. Base-pair changes were
      considered to be causative for ARVC if they were detected in an affected dog but
      not in unaffected dogs, and if they involved a conserved amino acid and changed
      that amino acid to one of a different polarity, acid-base status, or structure.
      RESULTS: A causative mutation for ARVC in Boxers was not identified, although
      single nucleotide polymorphisms were detected in some affected dogs within exon 3
      of the plakophilin-2 gene; exon 3 of the plakoglobin gene; exons 3 and 7 of the
      desmoglein-2 gene; and exons 6, 14, 15, and 24 of the desmoplakin gene. None of
      these changed the amino acid of the respective protein. CONCLUSIONS AND CLINICAL
      RELEVANCE: Mutations within the desmosomal genes associated with the development
      of ARVC in humans do not appear to be causative for ARVC in Boxers. Genomewide
      scanning for genetic loci of interest in dogs should be pursued.

PMID- 18052739
TI  - Evaluation of a bench-top coagulation analyzer for measurement of prothrombin
      time, activated partial thromboplastin time, and fibrinogen concentrations in
      healthy dogs.
AB  - OBJECTIVE: To evaluate a bench-top coagulation analyzer for determination of
      prothrombin time (PT), activated partial thromboplastin time (APTT), and
      fibrinogen concentration in healthy dogs. ANIMALS: 55 healthy adult dogs.
      PROCEDURES: PT, APTT, and fibrinogen concentration were determined by use of the
      coagulation analyzer. Values were compared with results obtained independently by
      a conventional laboratory. RESULTS: Correlations (with 95% confidence intervals)
      between the coagulation analyzer and conventional laboratory values were 0.760
      (0.610 to 0.857), 0.700 (0.448 to 0.721), and 0.896 (0.878 to 0.918) for PT,
      APTT, and fibrinogen concentration, respectively. Using linear regression,
      comparison of data from the coagulation analyzer and the conventional laboratory
      provided equations relating the coagulation analyzer values with values from the
      conventional laboratory and suggested that APTT and fibrinogen values from the
      coagulation analyzer and conventional laboratory were approximately the same
      within expected random variation. Prothrombin time values for the coagulation
      analyzer were significantly offset from the PT values for the conventional
      laboratory but still were correlated reasonably well with the conventional
      laboratory values. CONCLUSIONS AND CLINICAL RELEVANCE: By use of the mechanical
      method of analysis, fibrinogen concentrations obtained with a bench-top
      coagulation analyzer correlated well with results for a conventional laboratory,
      indicating that the coagulation analyzer is a reliable instrument for
      determination of this coagulation variable. Coagulation analyzer results for PT
      and APTT correlated less strongly with those for the conventional laboratory, but
      they would still be considered clinically reliable.

PMID- 18052740
TI  - Assessment of a point-of-care biochemical analyzer and comparison with a
      commercial laboratory for the measurement of total protein and albumin
      concentrations in psittacines.
AB  - OBJECTIVE: To determine agreement for total protein (TP) and albumin
      concentrations measured by a point-of-care biochemical analyzer in heparinized
      whole blood and plasma samples obtained from psittacines and compare results with
      those from a commercial laboratory. SAMPLE POPULATION: Hematologic samples from
      92 healthy birds. PROCEDURES: Duplicate samples of heparinized whole blood and
      plasma were obtained. A point-of-care biochemical analyzer was used to determine
      TP and albumin concentrations. To assess precision, intraclass correlation
      coefficient (r(i)) and Bland-Altman measures of agreement were used. These
      results were compared by use of Bland-Altman plots with those obtained from a
      commercial laboratory that used a biuret method for TP concentration and
      electrophoresis for albumin concentration. RESULTS: For the analyzer, there was
      excellent agreement (r(i) = 0.91) between heparinized whole blood and plasma
      samples for TP and albumin concentrations. Relative error was 0.9% for TP and
      0.7% for albumin. Analyzer results correlated well with commercial laboratory
      results, with a downward bias of 0.6 for TP and 0.3 for albumin. CONCLUSIONS AND
      CLINICAL RELEVANCE: The analyzer had excellent precision for analysis of
      heparinized whole blood or plasma samples for TP or albumin concentrations;
      analyzer values had good agreement with those from a commercial laboratory. The
      analyzer could be a valid method to measure plasma TP concentrations and provide
      point-of-care testing in apparently healthy parrots. Biochemical analyzer results
      for plasma albumin concentration were not validated by results from a commercial
      laboratory, so conclusions cannot be drawn regarding use of the analyzer in
      measurement of albumin concentrations in psittacines.

PMID- 18052741
TI  - Phosphodiesterase isoenzymes in equine platelets and their influence on platelet
      adhesion.
AB  - OBJECTIVE: To determine the phosphodiesterase (PDE) isoenzymes in equine
      platelets and evaluate their influence on platelet adhesion. SAMPLE POPULATION:
      Platelets obtained from healthy New Forest Pony geldings that ranged from 12 to
      20 years of age (mean +/- SEM, 17.3 +/- 1.1 years). PROCEDURES: PDE isoenzyme
      activity in equine platelets was determined by use of a 2-step radioactive assay.
      Functional importance of PDE isoenzymes was established by use of selective
      inhibitors in a colorimetric adhesion assay. RESULTS: PDE1, PDE2, PDE3, and PDE5
      and small amounts of PDE4 were found in equine platelets. Inhibition of PDE3
      abolished platelet adhesion almost completely, whereas inhibition of PDE4 and
      PDE5 had little effect. CONCLUSIONS AND CLINICAL RELEVANCE: Function of equine
      platelets can be influenced by inhibition of PDE3. Selective PDE3 inhibitors may
      be clinically useful to regulate platelet function. They offer the advantage of
      increased potency with fewer adverse effects, compared with those for
      nonselective PDE inhibitors.

PMID- 18052742
TI  - Effects of in vitro exposure to hay dust on expression of interleukin-17, -23, 
      8, and -1beta and chemokine (C-X-C motif) ligand 2 by pulmonary mononuclear cells
      isolated from horses chronically affected with recurrent airway disease.
AB  - OBJECTIVE: To examine effects of in vitro exposure to solutions of hay dust,
      lipopolysaccharide (LPS), or beta-glucan on cytokine expression in pulmonary
      mononuclear cells isolated from healthy horses and horses with recurrent airway
      obstruction (RAO). ANIMALS: 8 RAO-affected and 7 control horses (experiment 1)
      and 6 of the RAO-affected and 5 of the control horses (experiment 2). PROCEDURES:
      Bronchoalveolar lavage cells were isolated from horses that had been stabled and
      fed dusty hay for 14 days. Pulmonary mononuclear cells were incubated for 24
      (experiment 1) or 6 (experiment 2) hours with PBS solution or solutions of hay
      dust, beta-glucan, or LPS. Gene expression of interleukin (IL)-17, IL-23(p19 and
      p40 subunits), IL-8, IL-1beta, and chemokine (C-X-C motif) ligand 2 (CXCL2) was
      measured with a kinetic PCR assay. RESULTS: Treatment with the highest
      concentration of hay dust solution for 6 or 24 hours increased expression of IL
      23(p19 and p40), IL-8, and IL-1beta in cells from both groups of horses and
      increased early expression of IL-17 and CXCL2 in RAO-affected horses.
      Lipopolysaccharide upregulated early expression of IL-23(p40) and IL-8 in cells
      from both groups of horses but only late expression of these cytokines in cells
      from RAO-affected horses. Treatment with beta-glucan failed to increase cytokine
      expression at 6 or 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Cells from RAO
      affected horses were not more responsive to the ligands tested than were cells
      from control horses, which suggests a minimal role of mononuclear cells in
      propagation of airway neutrophilia in horses with chronic RAO.

PMID- 18052743
TI  - Epidemiologic characteristics of catastrophic musculoskeletal injuries in
      Thoroughbred racehorses.
AB  - OBJECTIVE: To determine characteristics, incidence rate, and possible
      associations with selected demographic characteristics of catastrophic
      musculoskeletal injuries (CMIs) in Thoroughbred racehorses. ANIMALS: 76
      Thoroughbreds with CMIs. PROCEDURES: Incidence rates of CMIs during racing or
      training were calculated with number of CMIs as the numerator and overall numbers
      of races or training events during 2004 and 2005 as the denominators. Exact 95%
      confidence intervals were calculated. Associations between incidence and
      dichotomous exposure factors, nominal factors, and ordinal factors were
      determined. Only univariable associations were examined. RESULTS: 76 horses were
      euthanized because of CMI and represented 2.36 and 1.69 deaths/1,000 racing
      starts in 2004 and 2005, respectively. Of these, 57 were euthanized within 60
      days before or after a race, which yielded a point incidence of 1.05/1,000 racing
      starts and 0.39/1,000 training starts. CONCLUSIONS AND CLINICAL RELEVANCE:
      Incidence rate of CMIs at 2 Ontario racetracks was similar to that at other North
      American racetracks. A cumulative death rate of 1 to 2 deaths/wk should be
      considered typical when designing prevention strategies and offers a baseline
      value for measuring improvement.

PMID- 18052744
TI  - Altered expression of versican and hyaluronan in melanocytic tumors of dogs.
AB  - OBJECTIVE: To analyze the expression of versican and hyaluronan in melanocytomas
      and malignant melanomas of dogs, to correlate their expression with expression of
      the hyaluronan receptor CD44, and to identify enzymes responsible for the
      synthesis and degradation of hyaluronan in canine dermal fibroblasts and canine
      melanoma cell lines. SAMPLE POPULATION: 35 biopsy specimens from melanocytic
      tumors of dogs, canine primary dermal fibroblasts, and 3 canine melanoma cell
      lines. PROCEDURES: Versican, hyaluronan, and CD44 were detected in tumor samples
      by use of histochemical or immunohistochemical methods. Expression of hyaluronan
      metabolizing enzymes was analyzed with a reverse transcriptase-PCR assay.
      RESULTS: Versican was found only in some hair follicles and around some blood
      vessels in normal canine skin, whereas hyaluronan was primarily found within the
      dermis. Hyaluronan was found in connective tissue of the oral mucosa. Versican
      and, to a lesser extent, hyaluronan were significantly overexpressed in malignant
      melanomas, compared with expression in melanocytomas. No significant difference
      was found between malignant tumors from oral or cutaneous origin. The expression
      of both molecules was correlated, but hyaluronan had a more extensive
      distribution than versican. Versican and hyaluronan were mainly associated with
      tumor stroma. Canine fibroblasts and melanoma cell lines expressed hyaluronan
      synthase 2 and 3 (but not 1) and hyaluronidase 1 and 2. CONCLUSIONS AND CLINICAL
      RELEVANCE: Versican may be useful as a diagnostic marker for melanocytic tumors
      in dogs. Knowledge of the enzymes involved in hyaluronan metabolism could reveal
      new potential therapeutic targets.

PMID- 18052745
TI  - Telomere length in normal and neoplastic canine tissues.
AB  - OBJECTIVE: To determine the mean telomere restriction fragment (TRF) length in
      normal and neoplastic canine tissues. SAMPLE POPULATION: 57 solid-tissue tumor
      specimens collected from client-owned dogs, 40 samples of normal tissue collected
      from 12 clinically normal dogs, and blood samples collected from 4 healthy blood
      donor dogs. PROCEDURES: Tumor specimens were collected from client-owned dogs
      during diagnostic or therapeutic procedures at the University of Illinois
      Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were
      collected from 12 control dogs. Telomere restriction fragment length was
      determined by use of an assay kit. A histologic diagnosis was provided for each
      tumor by personnel at the Veterinary Diagnostic Laboratory at the University of
      Illinois. RESULTS: Mean of the mean TRF length for 44 normal samples was 19.0
      kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for
      57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of
      the mean TRF length for tumors and normal tissues was identical, tumor samples
      had more variability in TRF length. CONCLUSIONS AND CLINICAL RELEVANCE:
      Telomerase, which represents the main mechanism by which cancer cells achieve
      immortality, is an attractive therapeutic target. The ability to measure telomere
      length is crucial to monitoring the efficacy of telomerase inhibition. In
      contrast to many other mammalian species, the length of canine telomeres and the
      rate of telomeric DNA loss are similar to those reported in humans, making dogs a
      compelling choice for use in the study of human anti-telomerase strategies.

PMID- 18052746
TI  - Effect of parenteral administration of erythromycin, tilmicosin, and tylosin on
      abomasal emptying rate in suckling calves.
AB  - OBJECTIVE: To determine the effect of parenteral administration of erythromycin,
      tilmicosin, and tylosin on abomasal emptying rate in suckling calves. ANIMALS: 8
      male Holstein-Friesian calves < 35 days old. PROCEDURES: Calves received each of
      4 treatments in random order (2 mL of saline [0.9% NaCl] solution, IM [control
      treatment]; erythromycin, 8.8 mg/kg, IM; tilmicosin, 10 mg/kg, SC; and tylosin,
      17.6 mg/kg, IM). Calves were fed 2 L of milk replacer containing acetaminophen
      (50 mg/kg) 30 minutes later. Jugular venous blood samples and transabdominal
      ultrasonographic abomasal dimensions were obtained periodically after suckling.
      Abomasal emptying rate was assessed on the basis of the time to maximal plasma
      acetaminophen concentration and ultrasonographic determination of the halftime of
      abomasal emptying. One-tailed Dunnett post tests were conducted whenever the F
      value for group was significant. RESULTS: Emptying rate was faster for
      erythromycin, tilimicosin, and tylosin than for the control treatment, as
      determined on the basis of time to maximal plasma acetaminophen concentration.
      Ultrasonography indicated that the half-time of abomasal emptying was
      significantly shorter for erythromycin than for the control treatment. Tylosin
      and tilmicosin accelerated the abomasal emptying rate, but not significantly,
      relative to the emptying rate for the control treatment. CONCLUSIONS AND CLINICAL
      RELEVANCE: Administration of erythromycin, tilmicosin, and tylosin at the label
      dosage increased abomasal emptying rate in calves. The clinical importance of an
      increase in abomasal emptying rate in cattle remains to be determined.

PMID- 18052747
TI  - Alteration of release and role of adenosine diphosphate and thromboxane A2 during
      collagen-induced aggregation of platelets from cattle with Chediak-Higashi
      syndrome.
AB  - OBJECTIVE: To compare the interaction of endogenous ADP with collagen and
      thromboxane A(2) (TXA(2)) during collagen-induced platelet aggregation between
      platelets from healthy cattle and those with Chediak-Higashi syndrome (CHS).
      POPULATION SAMPLE: Platelets harvested from blood samples from healthy Japanese
      Black cattle and those with CHS. PROCEDURES: Aggregation of gel-filtered
      platelets; release of ATP-ADP; and generation of thromboxane B(2) (TXB(2)), a
      metabolite of TXA(2), were measured. RESULTS: The potency of collagen to induce
      aggregation in platelets of cattle with CHS (ie, CHS platelets) was less than a
      tenth of that in platelets of healthy cattle (ie, control platelets). Platelet
      aggregation induced by collagen at an intermediate concentration depended on the
      coexistence of ADP and TXA(2), suggesting that released ADP cannot cause platelet
      aggregation by itself. Collagen-induced ADP release was markedly decreased,
      whereas TXB(2) production was slightly low in CHS platelets, compared with that
      in control platelets. A combination of subthreshold amounts of ADP and 9,11
      dideoxy-9alpha, 11alpha-methano-epoxy-prostaglandin F(2) (U46619), a TXA(2)
      analogue, caused platelet aggregation. Similarly, a combination of subthreshold
      amounts of collagen and ADP caused platelet aggregation, whereas collagen and
      U46619 were not synergistic. CONCLUSIONS AND CLINICAL RELEVANCE: Deficient ADP
      release ensuing from the delta-storage pool deficiency in platelets from cattle
      with CHS resulted in reduction of collagen-induced platelet aggregation, through
      attenuation of synergism between TXA(2) and ADP and between ADP and collagen.
      Furthermore, results of the study reported here indicated that TXA(2) was
      important for aggregation of bovine platelets.

PMID- 18052748
TI  - Comparison of the effects of caffeine and doxapram on respiratory and
      cardiovascular function in foals with induced respiratory acidosis.
AB  - OBJECTIVE: To determine and compare the effects of caffeine and doxapram on
      cardiorespiratory variables in foals during isoflurane-induced respiratory
      acidosis. ANIMALS: 6 clinically normal foals (1 to 3 days old). PROCEDURES: At
      intervals of > or = 24 hours, foals received each of 3 IV treatments while in a
      steady state of hypercapnia induced by isoflurane anesthesia (mean +/- SD, 1.4 +/
      0.3% endtidal isoflurane concentration). After assessment of baseline
      cardiorespiratory variables, a low dose of the treatment was administered and
      variables were reassessed; a high dose was then administered, and variables were
      again assessed. Sequential low- and high-dose treatments included doxapram
      (loading dose of 0.5 mg/kg, followed by a 20-minute infusion at 0.03 mg/kg/min
      and then 0.08 mg/kg/min), caffeine (5 mg/kg and 10 mg/kg), and saline (0.9% NaCl)
      solution (equivalent volumes). RESULTS: Administration of doxapram at both
      infusion rates resulted in a significant increase in respiratory rate, minute
      ventilation, arterial blood pH, PaO(2), and arterial blood pressure. These
      variables were also significantly higher during doxapram administration than
      during caffeine or saline solution administration. There was a significant dose
      dependent decrease in PaCO(2) and arterial bicarbonate concentration during
      doxapram treatment. In contrast, PaCO(2) increased from baseline values after
      administration of saline solution or caffeine. The PaCO(2) value was
      significantly lower during doxapram treatment than it was during caffeine or
      saline solution treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated
      that doxapram restored ventilation in a dose-dependent manner in neonatal foals
      with isoflurane-induced hypercapnia. The effects of caffeine on respiratory
      function were indistinguishable from those of saline solution.

PMID- 18052749
TI  - Fetal protection against continual exposure to bovine viral diarrhea virus
      following administration of a vaccine containing an inactivated bovine viral
      diarrhea virus fraction to cattle.
AB  - OBJECTIVE: To evaluate the efficacy of a commercially available killed bovine
      viral diarrhea virus (BVDV) vaccine to protect against fetal infection in
      pregnant cattle continually exposed to cattle persistently infected with the
      BVDV. ANIMALS: 60 crossbred beef heifers and 4 cows persistently infected with
      BVDV. PROCEDURES: Beef heifers were allocated to 2 groups. One group was
      vaccinated twice (21-day interval between the initial and booster vaccinations)
      with a commercially available vaccine against BVDV, and the other group served as
      nonvaccinated control cattle. Estrus was induced, and the heifers were bred.
      Pregnancy was confirmed by transrectal palpation. Four cows persistently infected
      with BVDV were housed with 30 pregnant heifers (15 each from the vaccinated and
      nonvaccinated groups) from day 52 to 150 of gestation. Fetuses were then
      harvested by cesarean section and tested for evidence of BVDV infection. RESULTS:
      1 control heifer aborted after introduction of the persistently infected cows.
      Bovine viral diarrhea virus was isolated from 14 of 14 fetuses obtained via
      cesarean section from control heifers but from only 4 of 15 fetuses obtained via
      cesarean section from vaccinated heifers; these proportions differed
      significantly. CONCLUSIONS AND CLINICAL RELEVANCE: A commercially available
      multivalent vaccine containing an inactivated BVDV fraction significantly reduced
      the risk of fetal infection with BVDV in heifers continually exposed to cattle
      persistently infected with BVDV. However, not all vaccinated cattle were
      protected, which emphasizes the need for biosecurity measures and elimination of
      cattle persistently infected with BVDV in addition to vaccination within a herd.

PMID- 18052750
TI  - Optimizing opioid management in palliative care.

PMID- 18052754
TI  - How important are BMD accuracy errors for the clinical interpretation of DXA
      scans?

PMID- 18052753
TI  - Effects of growth hormone administration on bone mineral metabolism, PTH
      sensitivity and PTH secretory rhythm in postmenopausal women with established
      osteoporosis.
AB  - INTRODUCTION: Growth hormone (GH) replacement improves target organ sensitivity
      to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover,
      and BMD in adult GH-deficient (AGHD) patients. In postmenopausal women with
      established osteoporosis, GH and insulin like growth factor-1 (IGF-1)
      concentrations are low, and administration of GH has been shown to increase bone
      turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH
      administration on PTH sensitivity, PTH circadian rhythm, and bone mineral
      metabolism in postmenopausal women with established osteoporosis. MATERIALS AND
      METHODS: Fourteen postmenopausal women with osteoporosis were compared with 14
      healthy premenopausal controls at baseline that then received GH for a period of
      12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH
      administration and half-hourly blood and 3-h urine samples were collected. PTH,
      calcium (Ca), phosphate (PO(4)), nephrogenous cyclic AMP (NcAMP), beta C
      telopeptide of type 1 collagen (betaCTX), procollagen type I amino-terminal
      propeptide (PINP), and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured.
      Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t-test
      and general linear model ANOVAs for repeated measures were used where
      appropriate. RESULTS: IGF-1 concentration was significantly lower in the women
      with established osteoporosis compared with controls (101.5 +/- 8.9 versus 140.9
      +/- 10.8 mug/liter; p < 0.05) and increased significantly after 1, 3, 6, and 12
      mo of GH administration (p < 0.001). Twenty-four-hour mean PTH concentration was
      higher in the osteoporotic women (5.4 +/- 0.1 pM) than in healthy controls (4.4
      +/- 0.1 pM, p < 0.001) and decreased after 1 (5.2 +/- 0.1 pM, p < 0.001), 3 (5.0
      +/- 0.1 pM, p < 0.001), 6 (4.7 +/- 0.1 pM, p < 0.001), and 12 mo (4.9 +/- 0.1 pM,
      p < 0.05) of GH administration compared with baseline. NcAMP was significantly
      lower in osteoporotic women (17.2 +/- 1.2 nM glomerular filtration rate [GFR])
      compared with controls (21.4 +/- 1.4 nM GFR, p < 0.05) and increased after 1
      (24.2 +/- 2.5 nM GFR, p < 0.05), 3 (27.3 +/- 1.5 nM GFR, p < 0.001), and 6 mo
      (32.4 +/- 2.5 nM GFR, p < 0.001) compared with baseline. PTH secretion was
      characterized by two peaks in premenopausal women and was altered in
      postmenopausal women with a sustained increase in PTH concentration. GH
      administration also restored a normal PTH secretory pattern in the osteoporotic
      women. The 24-h mean adjusted serum calcium (ACa) concentration increased at 1
      and 3 mo (p < 0.001) and PO(4) at 1, 3, 6, and 12 mo (p < 0.001). 1,25(OH)(2)D
      concentration increased after 3, 6, and 12 mo of GH (p < 0.05). An increase in
      urine Ca excretion was observed at 3 and 6 mo (p < 0.05), and the renal threshold
      for maximum tubular phosphate reabsorption rate (TmPO4/GFR) increased after 1, 3,
      6, and 12 mo (p < 0.05). betaCTX concentration increased progressively from 0.74
      +/- 0.07 mug/liter at baseline to 0.83 +/- 0.07 mug/liter (p < 0.05) at 1 mo and
      1.07 +/- 0.09 mug/liter (p < 0.01) at 3 mo, with no further increase at 6 or 12
      mo. PINP concentration increased progressively from baseline (60 +/- 5 mug/liter)
      to 6 mo (126 +/- 11 mug/liter, p < 0.001), with no further increase at 12 mo. The
      percentage increase in PINP concentration was significantly higher than betaCTX
      (p < 0.05). CONCLUSIONS: Our study shows that GH has a regulatory role in bone
      mineral metabolism. GH administration to postmenopausal osteoporotic women
      improves target organ sensitivity to PTH and bone mineral metabolism and alters
      PTH secretory pattern with greater increases in bone formation than resorption.
      These changes, resulting in a net positive bone balance, may partly explain the
      mechanism causing the increase in BMD after long-term administration of GH in
      postmenopausal women with osteoporosis shown in previous studies and proposes a
      further component in the development of age-related postmenopausal osteoporosis.

PMID- 18052755
TI  - Overexpression of Smurf2 stimulates endochondral ossification through
      upregulation of beta-catenin.
AB  - Ectopic expression of Smurf2 in chondrocytes and perichondrial cells accelerated
      endochondral ossification by stimulating chondrocyte maturation and osteoblast
      development through upregulation of beta-catenin in Col2a1-Smurf2 embryos. The
      mechanism underlying Smurf2-mediated morphological changes during embryonic
      development may provide new mechanistic insights and potential targets for
      prevention and treatment of human osteoarthritis. INTRODUCTION: Our recent
      finding that adult Col2a1-Smurf2 mice have an osteoarthritis-like phenotype in
      knee joints prompted us to examine the role of Smurf2 in the regulation of
      chondrocyte maturation and osteoblast differentiation during embryonic
      endochondral ossification. MATERIALS AND METHODS: We analyzed gene expression and
      morphological changes in developing limbs by immunofluorescence,
      immunohistochemistry, Western blot, skeletal preparation, and histology. A series
      of markers for chondrocyte maturation and osteoblast differentiation in
      developing limbs were examined by in situ hybridization. RESULTS: Ectopic
      overexpression of Smurf2 driven by the Col2a1 promoter was detected in
      chondrocytes and in the perichondrium/periosteum of 16.5 dpc transgenic limbs.
      Ectopic Smurf2 expression in cells of the chondrogenic lineage inhibited
      chondrocyte differentiation and stimulated maturation; ectopic Smurf2 in cells of
      the osteoblastic lineage stimulated osteoblast differentiation. Mechanistically,
      this could be caused by a dramatic increase in the expression of beta-catenin
      protein levels in the chondrocytes and perichondrial/periosteal cells of the
      Col2a1-Smurf2 limbs. CONCLUSIONS: Ectopic expression of Smurf2 driven by the
      Col2a1 promoter accelerated the process of endochondral ossification including
      chondrocyte maturation and osteoblast differentiation through upregulation of
      beta-catenin, suggesting a possible mechanism for development of osteoarthritis
      seen in these mice.

PMID- 18052756
TI  - In vivo determination of bone structure in postmenopausal women: a comparison of
      HR-pQCT and high-field MR imaging.
AB  - Bone structural measures obtained by two noninvasive imaging tools-3T MRI and HR
      pQCT-were compared. Significant but moderate correlations and 2- to 4-fold
      discrepancies in parameter values were detected, suggesting that differences in
      acquisition and analysis must be considered when interpreting data from these
      imaging modalities. INTRODUCTION: High-field MRI and high resolution (HR)-pQCT
      are currently being used in longitudinal bone structure studies. Substantial
      differences in acquisition and analysis between these modalities may influence
      the quantitative data produced and could potentially influence clinical decisions
      based on their results. Our goal was to compare trabecular and cortical bone
      structural measures obtained in vivo by 3T MRI and HR-pQCT. MATERIALS AND
      METHODS: Postmenopausal osteopenic women (n = 52) were recruited for this study.
      HR-pQCT imaging of the radius and tibia was performed using the XtremeCT scanner,
      with a voxel size of 82 x 82 x 82 microm(3). MR imaging was performed on a 3T
      Signa scanner using SSFP imaging sequences, with a pixel size of 156 x 156
      microm(2) and slice thickness of 500 microm. Structure parameters were calculated
      using standard HR-pQCT and MRI analysis techniques. Relationships between
      measures derived from HR-pQCT, MRI, and DXA were studied. RESULTS: Significant
      correlations between HR-pQCT and MRI parameters were found (p < 0.0001) and were
      strongest for Tb.N (r(2) = 0.52), Ct.Th (r(2) = 0.59), and site-specific Tb.Sp
      (r(2) = 0.54-0.60). MRI and HR-pQCT provided statistically different values of
      structure parameters (p < 0.0001), with BV/TV and Tb.Th exhibiting the largest
      discrepancies (MR/HR-pQCT = 3-4). Although differences in the Tb.N values were
      statistically significant, the mean differences were on the order of our
      reproducibility measurements. Systematic differences between MRI and HR-pQCT
      analysis procedures leading to discrepancies in cortical thickness values were
      observed, with MRI values consistently higher. Minimal correlations were found
      between MRI or HR-pQCT parameters and DXA BMD or T-score, except between HR-pQCT
      measures at the radius and the ultradistal radius T-scores, where moderate
      correlations were found (r(2) = 0.19-0.58). CONCLUSIONS: This study provides
      unique insight into two emerging noninvasive tools for bone structure evaluation.
      Our findings highlight the significant influence of analysis technique on results
      of in vivo assessment and underscore the importance of accounting for these
      differences when interpreting results from these modalities.

PMID- 18052757
TI  - Low-grade metabolic acidosis may be the cause of sodium chloride-induced
      exaggerated bone resorption.
AB  - Stepwise increase in NaCl intake in healthy male test subjects led to a low-grade
      metabolic acidosis. This was most likely the cause for increased bone resorption
      during high sodium chloride intake, as determined by analyzing bone resorption
      markers. INTRODUCTION: We examined the effect of increased dietary sodium
      chloride (NaCl) on bone metabolism and acid-base balance. MATERIALS AND METHODS:
      Subjects were nine healthy men (mean age, 25.7 +/- 3.1 yr; mean body weight [BW],
      71.5 +/- 4.0 kg). During the first period (6 days), subjects received 0.7 mEq
      NaCl/kg BW per day (phase 1), during the second period (6 days) 2.8 mEq NaCl/kg
      BW per day (phase 2), during the third period (10 days) 7.7 mEq NaCl/kg BW per
      day (phase 3), and during the fourth period (6 days) 0.7 mEq NaCl/kg BW per day
      (phase 4). RESULTS: Twenty-four-hour urinary excretion of calcium and sodium rose
      significantly with increasing NaCl intake (p < 0.001 for both). Urinary excretion
      of bone resorption markers C- and N-terminal telopeptide of type I collagen (CTX,
      NTX) increased from phase 2 to phase 3 (CTX, p = 0.013; NTX, p < 0.001) and
      decreased from phase 3 to phase 4 (CTX, p < 0.001; NTX, p = 0.002). Bone
      formation markers N-terminal propeptide of type I procollagen, bone-specific
      alkaline phosphatase, and osteocalcin remained unchanged from low to high NaCl
      intake. Blood pH levels decreased (p = 0.04) between phases 1 and 3. Blood
      bicarbonate (HCO(3)(-)) and base excess (BE) decreased from phases 1 to 3 (p <
      0.001 for both) and from phases 2-3 (HCO(3)(-), p = 0.003; BE, p = 0.015). Nearly
      all bone resorption markers and acid-base variables reached their baseline levels
      in phase 4. CONCLUSIONS: We conclude that low-grade metabolic acidosis may be the
      cause of NaCl-induced exaggerated bone resorption.

PMID- 18052759
TI  - EEG diagnosis of nonconvulsive status epilepticus: generalized periodic patterns-
      status or not?

PMID- 18052758
TI  - Differential bone metabolism between postmenopausal women with osteoarthritis and
      osteoporosis.
AB  - A comparative study of bone metabolism between postmenopausal women with
      osteoarthritis and osteoporosis showed that differential levels of bone
      remodeling markers, leptin, free leptin index, and osteoprotegerin might partly
      contribute to the proposed inverse relationship in bone mass between
      postmenopausal women with osteoarthritis and osteoporosis. INTRODUCTION:
      Osteoarthritis (OA) and osteoporosis (OP) are two common disorders affecting the
      quality of life in the elderly. The association between OA and OP has always been
      debated. The objective of this study was to compare bone metabolism between
      postmenopausal women with OA and OP. MATERIALS AND METHODS: A total of 120
      postmenopausal women with OA and OP (n = 60, respectively) were included in this
      comparative study. Anthropometric parameters and BMD at the spine and the
      proximal femur were measured. Serum leptin, soluble leptin receptor (sLR),
      osteoprotegerin (OPG), and bone remodeling markers, including bone-specific
      alkaline phosphatase (BALP), osteocalcin (OC), deoxypyridinoline cross-links
      (DPD), and cross-linked N-telopeptides of type I collagen (NTX), were quantified
      with commercial ELISA or EIA kits. Free leptin index (FLI) was also calculated by
      the ratio between serum leptin and sLR levels. RESULTS: Postmenopausal women with
      OA had higher body weight, body mass index, fat mass, and percentage of fat than
      those suffered from OP. Compared with the patients in OP group, the patients in
      OA group had significantly higher BMD values at all sites measured. Higher serum
      leptin and FLI and lower OPG levels were shown in the OA group (leptin: 31.22 +/-
      6.4 versus 26.50 +/- 9.27 ng/ml, p < 0.001; FLI: 3.20 +/- 1.02 versus 2.50 +/-
      0.95, p < 0.05; OPG: 4.75 +/- 1.97 versus 6.96 +/- 2.75 pM, p < 0.001), whereas
      lower serum OC and higher urine DPD were noted in the OP group (OC: 16.45 +/-
      8.45 versus 13.06 +/- 6.25 ng/ml, p < 0.05; DPD: 10.83 +/- 7.12 versus 15.29 +/-
      6.65 nM BCE/mM Cr, p < 0.001). Serum OPG levels negatively correlated with BMD at
      all sites assessed. However, no correlation was found between leptin and BMD.
      Only in the OA group di positive correlations exist between FLI and Z-score at
      the femoral neck and Ward's triangle region. After stepwise regression analysis,
      it was found that differential factors were able to predict the variance of BMD
      at different sites to a certain extent. CONCLUSIONS: Our study suggests that
      there are significant differences in bone metabolism between postmenopausal women
      with OA and OP and provides evidence for the inverse relationship between OA and
      OP. Differential levels of bone remodeling markers, leptin, FLI, and OPG may
      partly contribute to the proposed inverse relationship. Roles of leptin and its
      soluble receptor in bone metabolism regulation should be explored further.

PMID- 18052761
TI  - Role of tolcapone in the treatment of Parkinson's disease.
AB  - For decades, the cornerstone of treatment for Parkinson's disease (PD) has been
      levodopa, which provides a smooth clinical response early in the course of
      disease. However, many PD patients develop motor complications on long-term
      levodopa therapy. Catechol-O-methyltransferase (COMT) is a selective and widely
      distributed enzyme involved in the catabolism of levodopa. Tolcapone and
      entacapone are selective and potent COMT inhibitors that slow the metabolism of
      levodopa, thus prolonging its effects. While both drugs act peripherally,
      tolcapone also inhibits COMT in the CNS. Tolcapone has been shown to be an
      effective adjunct in the treatment of PD in Phase II and III clinical trials,
      improving motor fluctuations and reducing levodopa requirements. Rare reports of
      severe hepatotoxicity, however, limited tolcapone's implementation in the
      treatment of PD. A reappraisal of the data for tolcapone treatment in PD has
      found that this risk is very small if proper hepatic monitoring guidelines are
      followed. This article reviews the pharmacology and clinical data on tolcapone,
      with particular focus on drug safety and the future role of tolcapone therapy in
      the treatment of PD.

PMID- 18052762
TI  - Almotriptan: meeting today's needs in acute migraine treatment.
AB  - Migraine is a common disorder associated with considerable individual and
      economic burden. Triptans are recommended for the treatment of migraine of any
      severity in patients who have failed to gain adequate relief with nonspecific
      medication; early transition to triptans avoids prolonged morbidity in patients
      failing to respond to nonspecific medications. There is evidence that early
      intervention therapy with oral formulations in migraine, soon after the onset of
      an attack and when pain is still mild, improves efficacy. Seven different
      triptans are currently marketed, with differing pharmacologic, efficacy and
      tolerability profiles. Almotriptan has many positive features, which include
      rigorously demonstrated efficacy in sumatriptan nonresponders, as early therapy
      and in menstrual migraine. In addition, almotriptan has a favorable pharmacologic
      profile with a lack of clinically relevant pharmacokinetic interventions with
      other drugs, adverse reactions rate similar to placebo, superior cost
      effectiveness and excellent performance on composite clinical outcome measures
      that incorporate features of greatest importance to patients. Although effective
      in both triptan-naive and -experienced patients, and as both early and standard
      therapy, almotriptan shows greater efficacy in triptan-naive patients and as
      early treatment, and is consistently one of the preferred triptans in
      multiattribute decision-making analyses incorporating attributes of significance
      for patients and physicians. Therefore, almotriptan has many features that make
      it an ideal choice for a triptan-naive patient moving from nonspecific
      medication, a patient switching from another triptan owing to inefficacy or
      tolerability issues and patients being advised to take a triptan early in the
      course of a migraine attack.

PMID- 18052763
TI  - Hypnotic analgesia.
AB  - Hypnosis has been used for centuries to treat various types of pain problems.
      Anecdotal reports of its efficacy have been around since the early 1800 s, but
      only recently has sophisticated research advanced the field. This paper will
      summarize the theoretical and clinical foundations of hypnotic analgesia, as well
      as offer recommendations for increasing its efficacy and improving future
      research to advance the field.

PMID- 18052764
TI  - The promise of gene therapy for the treatment of epilepsy.
AB  - Gene therapy involves the transfer and expression of a therapeutic gene into a
      target tissue, and essentially represents an intervention that alters the
      instruction set of a cell having a dominant effect on the cell phenotype. Gene
      therapy techniques may provide a realistic therapeutic option for CNS disorders
      that are difficult to treat with conventional drugs, such as for drug-resistant
      focal epilepsies. Preclinical studies using a selection of 'therapeutic' genes
      delivered into the rodent brain showed significant reduction of seizures and
      inhibition of epileptogenesis, thus establishing the proof-of-principle evidence
      of the potential applicability of this technology to human epilepsy. The
      promising potential of gene therapy for the treatment of CNS pathologies still
      requires further investigation to improve the efficacy and the safety of this
      approach using clinically relevant experimental models. The recent advances in
      refining gene therapy tools and in methods of gene delivery make this innovative
      approach a definite possibility for therapeutic intervention.

PMID- 18052766
TI  - New approaches to understanding hallucinations in Parkinson's disease:
      phenomenology and possible origins.
AB  - The authors review current literature on hallucinations in Parkinson's disease
      (PD). Recent neuropathological studies showed that hallucinations occur in
      synucleinopathies and are a significant predictor of Lewy Body depositions.
      Therefore, hallucinations are a hallmark of PD and of dementia with Lewy Bodies.
      Visual hallucinations are mostly complex and kinematic; preserved or disturbed
      insight on the nature of hallucinations is a major prognostic factor, although
      eventually all hallucinators will present with reduced insight. Current theories
      on the origin of hallucinations point to visual dysfunction, dream overflow and
      cognitive impairment, yet objection can be raised on each one of the putative
      models of hallucinations. Understanding of the origin of hallucinations is
      required in order to develop treatments: all treatment evaluations were focused
      in general on psychosis, and only clozapine obtained positive evidence-based
      ratings on efficacy. However, it is likely that cholinesterase inhibitors,
      antipsychotics and anti-5-hydroxytryptamine(3) agents and drugs acting on sleep
      regulation will have different and perhaps opposite effects on different types of
      hallucinations, whether they are accompanied by disturbed insight, sleep
      disorders or other psychotic features. Further studies will try to separate
      phenomenology and responses to treatment and will investigate the relevance of
      concomitant sleep disorders and abnormality of frontoparietal networks involved
      in the attention process.

PMID- 18052765
TI  - Molecular pathways and genetic aspects of Parkinson's disease: from bench to
      bedside.
AB  - Idiopathic Parkinson's disease (PD) is a progressive neurodegenerative disease
      characterized by dopaminergic neuronal loss within the substantia nigra. The
      incidence and prevalence of PD is rising with an increasing aging population. PD
      is a slowly progressive condition and patients can develop debilitating motor and
      functional impairment. Current research has implicated oxidative stress, alpha
      synucleinopathy and dysfunction of the ubiquitin-proteasome system in the
      pathogenesis of PD. A number of gene mutations have also been linked to the
      development of PD. The elucidation of these new molecular pathways has increased
      our knowledge of PD pathophysiology. This article reviews important molecular
      mechanisms and genetic causes implicated in the pathogenesis of PD, which has led
      to new areas of therapeutic drug research.

PMID- 18052767
TI  - Sudden unexpected death in epilepsy.
AB  - Mortality in people with epilepsy is two- to three-times that of the general
      population. This can be attributed to epilepsy itself (epilepsy-related death) or
      to the underlying cause of the epilepsy. Sudden unexpected death in epilepsy
      (SUDEP) is the commonest cause of epilepsy-related death. It is a syndrome where
      a person with epilepsy dies suddenly and no other cause of death is found. There
      are frequent reports of persons dying alone in their sleep. It is assumed that
      death occurs following a seizure but since the deaths are often unwitnessed this
      is only an assumption. The most important risk factor appears to be poor seizure
      control. Lately, SUDEP has received much public interest, has been the subject of
      international forums, ethical debates and comprises part of national guidelines
      on epilepsy management. Despite its high profile, the evidence for specific risk
      factors and pathophysiology is still not established. Poor incident case
      reporting, inaccurate death certification and fewer post-mortem examinations have
      limited the value of epidemiological data on SUDEP. Here, we review the
      characteristics of SUDEP, its likely risk factors, mechanisms and differential
      diagnosis, and consider possible strategies for prevention. We also explore the
      discussion of SUDEP with patients and the management of relatives of SUDEP
      patients.

PMID- 18052768
TI  - Vagus nerve stimulation for the treatment of intractable epilepsy.
AB  - Vagus nerve stimulation is a safe and reliable treatment adjunct for patients
      with medically intractable epilepsy. It is both a preventive and abortive form of
      therapy, potentially effective against both partial and generalized seizures in
      adults and children. Vagus nerve stimulation also has a number of serendipitous
      effects on mood, memory and attention, and has been approved for the treatment of
      refractory depression. Owing to its pleiotropic effects, it also holds promise
      for several other diseases. Its principal limitations are its unknown mechanism
      of action, the low likelihood of complete cure and the inability to predict which
      patients will derive substantial benefit. This article reviews the theoretical
      rationale, practical background and clinical applications of vagus nerve
      stimulation therapy.

PMID- 18052769
TI  - Tramadol extended-release formulations in the management of pain due to
      osteoarthritis.
AB  - Tramadol is a centrally acting, synthetic analgesic. Its mechanism of action
      involves weak binding to the mu-opioid receptors and inhibition of reuptake of
      both norepinephrine and serotonin. It has been used to treat moderate-to-severe
      pain for 30 years in Europe and more than 10 years in the USA. Initially
      available in immediate-release form (dosing four- to six-times daily), in recent
      years, a variety of once-daily formulations have been developed utilizing
      different extended-release technologies, which provide different pharmacokinetic
      characteristics (time to reach therapeutic plasma levels, time to steady state
      and plasma levels at 24 h), leading to different clinical implications (e.g.,
      titration schedule, time to onset and adverse events). This review addresses the
      efficacy and safety of the four marketed once-daily formulations with published
      data in studies on osteoarthritis. Analgesic efficacy and safety results from
      double-blind clinical studies utilizing 100-400 mg daily doses of these once
      daily formulations have been published. Most subjects took tramadol 200 or 300
      mg/day. Each once-daily formulation demonstrated statistically superior efficacy
      compared with placebo or similar efficacy to immediate-release or twice-daily
      tramadol. Availability of short- and long-term safety data varies among the
      formulations. Generally, adverse events are typical of tramadol (constipation,
      nausea, dizziness and somnolence). Descriptively, a trend to comparable or lower
      incidence and severity of adverse events seems apparent with the various once
      daily formulations. Tramadol once-daily formulations are more effective than
      placebo and at least as effective and well tolerated as immediate-release
      formulations in the treatment of pain due to osteoarthritis, and offer a reduced
      dosing regimen, which is especially valuable in elderly patients.

PMID- 18052770
TI  - Neurostimulation in primary headache syndromes.
AB  - Neurostimulation therapy involves the use of peripheral or central nerve
      electrical stimulation approaches for the treatment of medically intractable
      headache. Currently, for peripheral stimulation the main approach is that of
      occipital nerve stimulation, while for central stimulation deep-brain approaches
      with the target of the region of the posterior hypothalamic gray matter have been
      explored. Target conditions include migraine and the trigeminal autonomic
      cephalalgias: cluster headache, paroxysmal hemicrania and short-lasting
      unilateral neuralgiform headache attacks with conjunctival injection and
      tearing/cranial autonomic features (SUNCT/SUNA), as well as hemicrania continua.
      The initial results are encouraging and given the very significant disability of
      medically intractable primary headaches, this is a very promising area for
      patients and physicians alike.

PMID- 18052771
TI  - Current perspectives in the management of hyponatremia: prevention of CPM.
AB  - Central pontine myelinolysis represents a relatively contemporary neurologic
      entity in which an imbalance of water relative to alterations in the body's
      electrolyte levels induces characteristic demyelination in the central part of
      the basis pontis as well as extrapontine sites. The clinical scenario is
      typically one of chronic hyponatremia followed by a rapid correction to
      normonatremic or hypernatremic levels. This seemingly innocuous series of events
      can result in fatal consequences. Better understanding of the pathophysiology of
      this disorder provides avenues for clinical management, including use of steroids
      and organic osmoles, such as myoinositol. More recently, the introduction of a
      newer class of pharmacologic agents - the vasopressin receptor antagonists, known
      as vaptans, which induce an excretion of increased amounts of water without
      altered sodium or potassium excretion - is of particular interest. This review
      addresses classic approaches to the management of this disorder along with a
      discussion of newer pharmacologic agents that may become important therapeutic
      interventions in the clinical management of the osmotic myelinolysis syndrome.

PMID- 18052772
TI  - Sleep problems associated with ADHD: a review of current therapeutic options and
      recommendations for the future.
AB  - In recent years, there has been a growing interest in sleep problems associated
      with attention-deficit/hyperactivity disorder (ADHD). The etiology of these sleep
      problems is multifactorial. In this paper, we review the current literature on
      the treatment of the most common disorders or factors underlying sleep problems
      associated with ADHD. In particular, we focus on the management of sleep problems
      associated with ADHD medications, restless legs syndrome, excessive nocturnal
      motricity in sleep, sleep disordered breathing, sleep-onset insomnia and
      psychiatric comorbidities associated with ADHD. Given the paucity of randomized,
      controlled, double-blinded, placebo-controlled studies, it is hoped that this
      review will encourage further methodologically sound studies in order to be able
      to develop treatment guidelines.

PMID- 18052773
TI  - Optimal search space for clustering gene expression data via consensus.
AB  - Ensemble clustering methods have become increasingly important to ease the task
      of choosing the most appropriate cluster algorithm for a particular data analysis
      problem. The consensus clustering (CC) algorithm is a recognized ensemble
      clustering method that uses an artificial intelligence technique to optimize a
      fitness function. We formally prove the existence of a subspace of the search
      space for CC, which contains all solutions of maximal fitness and suggests two
      greedy algorithms to search this subspace. We evaluate the algorithms on two gene
      expression data sets and one synthetic data set, and compare the result with the
      results of other ensemble clustering approaches.

PMID- 18052774
TI  - Improved covariance matrix estimators for weighted analysis of microarray data.
AB  - Empirical Bayes models have been shown to be powerful tools for identifying
      differentially expressed genes from gene expression microarray data. An example
      is the WAME model, where a global covariance matrix accounts for array-to-array
      correlations as well as differing variances between arrays. However, the existing
      method for estimating the covariance matrix is very computationally intensive and
      the estimator is biased when data contains many regulated genes. In this paper,
      two new methods for estimating the covariance matrix are proposed. The first
      method is a direct application of the EM algorithm for fitting the multivariate t
      distribution of the WAME model. In the second method, a prior distribution for
      the log fold-change is added to the WAME model, and a discrete approximation is
      used for this prior. Both methods are evaluated using simulated and real data.
      The first method shows equal performance compared to the existing method in terms
      of bias and variability, but is superior in terms of computer time. For large
      data sets (>15 arrays), the second method also shows superior computer run time.
      Moreover, for simulated data with regulated genes the second method greatly
      reduces the bias. With the proposed methods it is possible to apply the WAME
      model to large data sets with reasonable computer run times. The second method
      shows a small bias for simulated data, but appears to have a larger bias for real
      data with many regulated genes.

PMID- 18052775
TI  - Protein local structure alignment under the discrete Frechet distance.
AB  - Protein structure alignment is a fundamental problem in computational and
      structural biology. While there has been lots of experimental/heuristic methods
      and empirical results, very few results are known regarding the
      algorithmic/complexity aspects of the problem, especially on protein local
      structure alignment. A well-known measure to characterize the similarity of two
      polygonal chains is the famous Frechet distance, and with the application of
      protein-related research, a related discrete Frechet distance has been used
      recently. In this paper, following the recent work of Jiang et al. we investigate
      the protein local structural alignment problem using bounded discrete Frechet
      distance. Given m proteins (or protein backbones, which are 3D polygonal chains),
      each of length O(n), our main results are summarized as follows: * If the number
      of proteins, m, is not part of the input, then the problem is NP-complete;
      moreover, under bounded discrete Frechet distance it is NP-hard to approximate
      the maximum size common local structure within a factor of n(1-epsilon). These
      results hold both when all the proteins are static and when translation/rotation
      are allowed. * If the number of proteins, m, is a constant, then there is a
      polynomial time solution for the problem.

PMID- 18052776
TI  - Bayesian hierarchical model for large-scale covariance matrix estimation.
AB  - Many bioinformatics problems implicitly depend on estimating large-scale
      covariance matrix. The traditional approaches tend to give rise to high variance
      and low accuracy due to "overfitting." We cast the large-scale covariance matrix
      estimation problem into the Bayesian hierarchical model framework, and introduce
      dependency between covariance parameters. We demonstrate the advantages of our
      approaches over the traditional approaches using simulations and OMICS data
      analysis.

PMID- 18052777
TI  - The neural integration of speaker and message.
AB  - When do listeners take into account who the speaker is? We asked people to listen
      to utterances whose content sometimes did not match inferences based on the
      identity of the speaker (e.g., "If only I looked like Britney Spears" in a male
      voice, or "I have a large tattoo on my back" spoken with an upper-class accent).
      Event-related brain responses revealed that the speaker's identity is taken into
      account as early as 200-300 msec after the beginning of a spoken word, and is
      processed by the same early interpretation mechanism that constructs sentence
      meaning based on just the words. This finding is difficult to reconcile with
      standard "Gricean" models of sentence interpretation in which comprehenders
      initially compute a local, context-independent meaning for the sentence
      ("semantics") before working out what it really means given the wider
      communicative context and the particular speaker ("pragmatics"). Because the
      observed brain response hinges on voice-based and usually stereotype-dependent
      inferences about the speaker, it also shows that listeners rapidly classify
      speakers on the basis of their voices and bring the associated social stereotypes
      to bear on what is being said. According to our event-related potential results,
      language comprehension takes very rapid account of the social context, and the
      construction of meaning based on language alone cannot be separated from the
      social aspects of language use. The linguistic brain relates the message to the
      speaker immediately.

PMID- 18052778
TI  - Cerebral lateralization of frontal lobe language processes and lateralization of
      the posterior visual word processing system.
AB  - The brain areas involved in visual word processing rapidly become lateralized to
      the left cerebral hemisphere. It is often assumed this is because, in the vast
      majority of people, cortical structures underlying language production are
      lateralized to the left hemisphere. An alternative hypothesis, however, might be
      that the early stages of visual word processing are lateralized to the left
      hemisphere because of intrinsic hemispheric differences in processing low-level
      visual information as required for distinguishing fine-grained visual forms such
      as letters. If the alternative hypothesis was correct, we would expect posterior
      occipito-temporal processing stages still to be lateralized to the left
      hemisphere for participants with right hemisphere dominance for the frontal lobe
      processes involved in language production. By analyzing event-related potentials
      of native readers of French with either left hemisphere or right hemisphere
      dominance for language production (determined using a verb generation task), we
      were able to show that the posterior occipito-temporal areas involved in visual
      word processing are lateralized to the same hemisphere as language production.
      This finding could suggest top-down influences in the development of posterior
      visual word processing areas.

PMID- 18052780
TI  - Tracking the location of visuospatial attention in a contingent capture paradigm.
AB  - Currently, there is considerable controversy regarding the degree to which top
      down control can affect attentional capture by salient events. According to the
      contingent capture hypothesis, attentional capture by a salient stimulus is
      contingent on a match between the properties of the stimulus and top-down
      attentional control settings. In contrast, bottom-up saliency accounts argue that
      the initial capture of attention is determined solely by the relative salience of
      the stimulus, and the effect of top-down attentional control is limited to
      effects on the duration of attentional engagement on the capturing stimulus. In
      the present study, we tested these competing accounts by utilizing the N2pc event
      related potential component to track the locus of attention during an attentional
      capture task. The results were completely consistent with the contingent capture
      hypothesis: An N2pc wave was elicited only by distractors that possessed the
      target-defining attribute. In a second experiment, we expanded upon this finding
      by exploring the effect of target-distractor similarity on the duration that
      attention dwells at the distractor location. In this experiment, only distractors
      possessing the target-defining attribute (color) captured visuospatial attention
      to their location and the N2pc increased in duration and in magnitude when the
      capture distractor also shared a second target attribute (category membership).
      Finally, in three additional control experiments, we replicated the finding of an
      N2pc generated by distractors, only if they shared the target-defining attribute.
      Thus, our results demonstrate that attentional control settings influence both
      which stimuli attract attention and to what extent they are processed.

PMID- 18052779
TI  - Binding 3-D object perception in the human visual cortex.
AB  - How do visual luminance, shape, motion, and depth bind together in the brain to
      represent the coherent percept of a 3-D object within hundreds of milliseconds
      (msec)? We provide evidence from simultaneous magnetoencephalographic (MEG) and
      electroencephalographic (EEG) data that perception of 3-D objects defined by
      luminance or motion elicits sequential activity in human visual cortices within
      500 msec. Following activation of the primary visual cortex around 100 msec, 3-D
      objects elicited sequential activity with only little overlap (dynamic 3-D
      shapes: MT-LO-Temp; stationary 3-D shapes: LO-Temp). A delay of 80 msec, both in
      MEG/EEG responses and in reaction times (RTs), was found when additional motion
      information was processed. We also found significant positive correlations
      between RT, and MEG and EEG responses in the right temporal location. After about
      400 msec, long-lasting activity was observed in the parietal cortex and
      concurrently in previously activated regions. Novel time-frequency analyses
      indicate that the activity in the lateral occipital (LO) complex is associated
      with an increase of induced power in the gamma band, a hallmark of binding. The
      close correspondence of an induced gamma response with concurrent sources located
      in the LO in both experimental conditions at different points in time (
      approximately 200 msec for luminance and approximately 300 msec for dynamic cues)
      strongly suggests that the LO is the key region for the assembly of object
      features. The assembly is fed forward to achieve coherent perception of a 3-D
      object within 500 msec.

PMID- 18052781
TI  - Activity of primate orbitofrontal and dorsolateral prefrontal neurons: effect of
      reward schedule on task-related activity.
AB  - Recent studies show that task-related activity in the dorsolateral prefrontal
      cortex (DLPFC) is modulated by the quality and quantity of the reward, suggesting
      that the subject's motivational state affects cognitive operations in the DLPFC.
      The orbito-frontal cortex (OFC) is a possible source of motivational inputs to
      the DLPFC. However, it is not well known whether these two areas exhibit similar
      motivational effects on task-related activity. We compared motivational effects
      on task-related activity in these areas while a monkey performed an oculomotor
      delayed-response (ODR) task under two reward schedules. In the ODR-1 schedule,
      reward was given only after the successful completion of four consecutive trials,
      whereas in the ODR-2 schedule, reward was given after every correct trial. Task
      related activities in both areas showed spatial selectivity. The spatial
      characteristics of task-related activity remained constant in both schedules.
      Task-related activity in both areas, especially delay-period activity, was also
      affected by the reward schedule and the magnitude of the activity gradually
      increased depending on the proximity of the reward trial in the ODR-1 schedule.
      More task-related OFC activities were affected by reward schedules, whereas more
      task-related DLPFC activities were affected by spatial factors and reward
      schedules. These results indicate that the OFC plays a role in monitoring the
      proximity of the reward trial and detecting reward delivery, whereas the DLPFC
      plays a role in performing cognitive operations and integrating cognitive and
      motivational information. These results also indicate that spatial information
      and the animal's motivational state independently affect neuronal activity in
      both areas.

PMID- 18052782
TI  - Neural correlates of preparation for action selection as a function of specific
      task demands.
AB  - Our behavior is frequently guided by rules, or prescribed guides for action. The
      prefrontal cortex (PFC) has been implicated in the ability to retrieve and use
      rules in a conscious, effortful manner. Several functional magnetic resonance
      imaging (fMRI) studies have examined the role of the PFC in rule representation;
      however, the precise PFC subregions implicated in this function vary from study
      to study. This observation raises the question of whether there are distinct
      classes of rules that are represented differentially in the brain. To address
      this question, an fMRI study was conducted in which participants performed two
      tasks, each at two levels of difficulty, during acquisition of event-related fMRI
      data. The response competition task was based on the Stroop paradigm:
      Participants were cued to determine either the ink color or color name associated
      with a word stimulus. In contrast, the paired associates task evaluated
      participants' memory for either one or four previously memorized pairs of words.
      On each trial, an instructional cue appeared briefly on the screen, followed by
      an 8-sec delay and a probe period. The left ventrolateral PFC (VLPFC) and the
      left supplementary motor area (SMA)/pre-SMA were engaged during the delay period
      for all conditions, consistent with a general role in rule representation. In
      contrast, different parts of the dorsolateral PFC, the anterior PFC, and the
      right VLPFC were preferentially engaged by one or both of the more challenging
      rules, consistent with the idea that rules are represented by partially distinct
      brain structures according to their content.

PMID- 18052783
TI  - Lexical-semantic activation in Broca's and Wernicke's aphasia: evidence from eye
      movements.
AB  - Lexical processing requires both activating stored representations and selecting
      among active candidates. The current work uses an eye-tracking paradigm to
      conduct a detailed temporal investigation of lexical processing. Patients with
      Broca's and Wernicke's aphasia are studied to shed light on the roles of anterior
      and posterior brain regions in lexical processing as well as the effects of
      lexical competition on such processing. Experiment 1 investigates whether objects
      semantically related to an uttered word are preferentially fixated, for example,
      given the auditory target "hammer," do participants fixate a picture of a nail?
      Results show that, like normal controls, both groups of patients are more likely
      to fixate on an object semantically related to the target than an unrelated
      object. Experiment 2 explores whether Broca's and Wernicke's aphasics show
      competition effects when words share onsets with the uttered word, for instance,
      given the auditory target "hammer," do participants fixate a picture of a
      hammock? Experiment 3 investigates whether these patients activate words
      semantically related to onset competitors of the uttered word, for example, given
      the auditory target "hammock," do participants fixate a nail due to partial
      activation of the onset competitor hammer? Results of Experiments 2 and 3 show
      pathological patterns of performance for both Broca's and Wernicke's aphasics
      under conditions of lexical onset competition. However, the patterns of deficit
      differed, suggesting different functional and computational roles for anterior
      and posterior areas in lexical processing. Implications of the findings for the
      functional architecture of the lexical processing system and its potential neural
      substrates are considered.

PMID- 18052784
TI  - Dissociable neural effects of task order control and task set maintenance during
      dual-task processing.
AB  - The functional relevance of the lateral prefrontal cortex (lPFC) for the ability
      to process two tasks simultaneously has been debated extensively in previous
      studies that employed functional magnetic resonance imaging (fMRI) to investigate
      the neural correlates of dual-task processing. In the present fMRI study, we shed
      new light on this debate by directly comparing the lPFC activity changes for two
      cognitive functions commonly associated with dual-task performance: task order
      control and task set maintenance. We manipulated both functions in a 2 x 2
      integrated parametric design. The fMRI data revealed a functional-neuroanatomical
      dissociation for the lPFC. Regions surrounding the inferior frontal sulcus and
      the middle frontal gyrus were exclusively associated with task order control but
      not with increased demands on task set maintenance during dual-task processing.
      The only lPFC region associated with task set maintenance was located in the left
      anterior insula. Outside the lPFC, we found dissociable regions for task order
      control and task set maintenance bilaterally in the premotor cortices with more
      rostral premotor activity for task order control and more caudal premotor
      activity for task set maintenance. In addition, task order control activated the
      intraparietal sulci bilaterally. Our data clearly suggest that task order control
      is a separable cognitive mechanism in dual-task situations that is related to
      activity changes in the lPFC and that can be dissociated from task set
      maintenance.

PMID- 18052785
TI  - Error and deviance processing in implicit and explicit sequence learning.
AB  - In this experiment, we examined the extent to which error-driven learning may
      operate under implicit learning conditions. We compared error monitoring in a
      sequence learning task in which stimuli consisted of regular, irregular, or
      random sequences. Subjects were either informed (explicit condition) or not
      informed (implicit condition) about the existence of the sequence. For both
      conditions, reaction times were faster to stimuli from regular sequences than
      from random sequences, thus supporting the view that sequence learning occurs
      irrespective of learning condition. Response-locked event-related potentials
      (ERPs) showed a pronounced ERN/Ne, thereby signaling the detection of committed
      errors. Deviant stimuli from irregular sequences elicited an N2b component that
      developed in the course of the experiment, albeit faster for explicit than
      implicit learners. This observation supports the view that deviant events acquire
      the status of perceived errors during explicit and implicit learning, and thus,
      an N2b is generated resembling the ERN/Ne to committed errors. While performing
      the task, expectations about upcoming events are generated, compared to the
      actual events, and evaluated on the dimension "better or worse than expected."
      The accuracy of this process improves with learning, as shown by a gradual
      increase in N2b amplitude as a function of learning. Additionally, a P3b, which
      is thought to mirror conscious processing of deviant stimuli and is related to
      updating of working memory representations, was found for explicit learners only.

PMID- 18052786
TI  - Distinct processing of objects and faces in the infant brain.
AB  - Previous work has shown that gamma-band electroencephalogram oscillations
      recorded over the posterior cortex of infants play a role in maintaining object
      representations during occlusion. Although it is not yet known what kind of
      representations are reflected in these oscillations, behavioral data suggest that
      young infants maintain spatiotemporal (but not featural) information during the
      occlusion of graspable objects, and surface feature (but not spatiotemporal)
      information during the occlusion of faces. To further explore this question, we
      presented infants with an occlusion paradigm in which they would, on half of the
      trials, see surface feature violations of either a face or an object. Based on
      previous studies, we predicted higher gamma-band activation when infants were
      presented with a surface feature violation of a face, but not of an object. These
      results were confirmed. A further analysis revealed that whereas infants
      exhibited a significant increase in gamma during the occlusion of an object (as
      reported in previous studies), no such increase was evident during the occlusion
      of a face. These data suggest markedly different processing of objects and faces
      in the infant brain and, furthermore, indicate that the representation
      underpinned by the posterior gamma increase may contain only spatiotemporal
      information.

PMID- 18052787
TI  - "Brain is to thought as stomach is to ??": investigating the role of
      rostrolateral prefrontal cortex in relational reasoning.
AB  - Brain imaging studies suggest that the rostrolateral prefrontal cortex (RLPFC),
      is involved in relational reasoning. Functional magnetic resonance imaging (fMRI)
      studies involving Raven's Progressive Matrices or verbal propositional analogies
      indicate that the RLPFC is engaged by tasks that require integration across
      multiple relational structures. Several studies have shown that the RLPFC is more
      active when people must evaluate an analogy (e.g., Is shoe to foot as glove is to
      hand?) than when they must simply evaluate two individual semantic relationships,
      consistent with the hypothesis that this region is important for relational
      integration. The current fMRI investigation further explores the role of the
      RLPFC in reasoning and relational integration by comparing RLPFC activation
      across four different propositional analogy conditions. Each of the four
      conditions required either relation completion (e.g., Shoe is to foot as glove is
      to WHAT? --> "hand") or relation comparison (e.g., Is shoe to foot as glove is to
      hand? --> "yes"). The RLPFC was engaged more strongly by the comparison subtask
      relative to completion, suggesting that the RLPFC is particularly involved in
      comparing relational structures.

PMID- 18052788
TI  - Syntactic and thematic constraint effects on blood oxygenation level dependent
      signal correlates of comprehension of relative clauses.
AB  - The effects of plausibility of thematic role assignment and syntactic structure
      on blood oxygenation level dependent (BOLD) signal were studied using event
      related functional magnetic resonance imaging by orthogonally varying syntactic
      structure (subject-vs. object-extracted relative clauses) and the plausibility of
      nouns playing thematic roles (constrained vs. unconstrained sentences) in a
      plausibility judgment task. In plausible sentences, BOLD signal increased for
      object-compared to subject-extracted clauses in unconstrained sentences in left
      middle temporal and left inferior frontal areas, for this contrast in constrained
      sentences in left middle temporal but not left inferior frontal areas, and for
      constrained subject-extracted sentences compared to unconstrained subject
      extracted sentences in the left inferior frontal gyrus and the left dorsolateral
      prefrontal cortex. We relate these areas of activation to the assignment of the
      syntactic structure of object-compared to subject-extracted structures and the
      process of checking which thematic roles activated in the course of processing a
      sentence are licensed by the syntactic structure of the sentence.

PMID- 18052789
TI  - Processing nouns and verbs in the left frontal cortex: a transcranial magnetic
      stimulation study.
AB  - Neuropsychological and neurophysiological studies suggest that the production of
      verbs in speech depends on cortical regions in the left frontal lobe. However,
      the precise topography of these regions, and their functional roles in verb
      production, remains matters of debate. In an earlier study with repetitive
      transcranial magnetic stimulation (rTMS), we showed that stimulation to the left
      anterior midfrontal gyrus disrupted verb production, but not noun production, in
      a task that required subjects to perform simple morphological alternations. This
      result raises a number of questions: for example, is the effect of stimulation
      focal and specific to that brain region? Is the behavioral effect limited to rule
      based, regular transformations, or can it be generalized over the grammatical
      category? In the present study, we used rTMS to suppress the excitability of
      distinct parts of the left prefrontal cortex to assess their role in producing
      regular and irregular verbs compared to nouns. We compared rTMS to sham
      stimulation and to stimulation of homologous areas in the right hemisphere.
      Response latencies increased for verbs, but were unaffected for nouns, following
      stimulation to the left anterior midfrontal gyrus. No significant interference
      specific for verbs resulted after stimulation to two other areas in the left
      frontal lobe, the posterior midfrontal gyrus and Broca's area. These results
      therefore reinforce the idea that the left anterior midfrontal cortex is critical
      for processing verbs. Moreover, none of the regions stimulated was preferentially
      engaged in the production of regular or irregular inflection, raising questions
      about the role of the frontal lobes in processing inflectional morphology.

PMID- 18052790
TI  - The functional effect of transcranial magnetic stimulation: signal suppression or
      neural noise generation?
AB  - Transcranial magnetic stimulation (TMS) is a popular tool for mapping perceptual
      and cognitive processes in the human brain. It uses a magnetic field to stimulate
      the brain, modifying ongoing activity in neural tissue under the stimulating
      coil, producing an effect that has been likened to a "virtual lesion." However,
      research into the functional basis of this effect, essential for the
      interpretation of findings, lags behind its application. Acutely, TMS may disable
      neuronal function, thereby interrupting ongoing neural processes. Alternatively,
      the effects of TMS have been attributed to an injection of "neural noise,"
      consistent with its immediate and effectively random depolarization of neurons.
      Here we apply an added-noise paradigm to test these alternatives. We delivered
      TMS to the visual cortex and measured its effect on a simple visual
      discrimination task, while concurrently manipulating the level of image noise in
      the visual stimulus itself. TMS increased thresholds overall; and increasing the
      amount of image noise systematically increased discrimination thresholds.
      However, these two effects were not independent. Rather, TMS interacted
      multiplicatively with the image noise, consistent with a reduction in the
      strength of the visual signal. Indeed, in this paradigm, there was no evidence
      that TMS independently added noise to the visual process. Thus, our findings
      indicate that the "virtual lesion" produced by TMS can take the form of a loss of
      signal strength which may reflect a momentary interruption to ongoing neural
      processing.

PMID- 18052791
TI  - Ventromedial frontal lobe plays a critical role in facial emotion recognition.
AB  - The ventromedial prefrontal cortex has been implicated in a variety of emotion
      processes. However, findings regarding the role of this region specifically in
      emotion recognition have been mixed. We used a sensitive facial emotion
      recognition task to compare the emotion recognition performance of 7 subjects
      with lesions confined to ventromedial prefrontal regions, 8 subjects with lesions
      elsewhere in prefrontal cortex, and 16 healthy control subjects. We found that
      emotion recognition was impaired following ventromedial, but not dorsal or
      lateral, prefrontal damage. This impairment appeared to be quite general, with
      lower overall ratings or more confusion between all six emotions examined. We
      also explored the relationship between emotion recognition performance and the
      ability of the same patients to experience transient happiness and sadness during
      a laboratory mood induction. We found some support for a relationship between
      sadness recognition and experience. Taken together, our results indicate that the
      ventromedial frontal lobe plays a crucial role in facial emotion recognition, and
      suggest that this deficit may be related to the subjective experience of emotion.

PMID- 18052792
TI  - Adenovirus-mediated gene delivery rescues a neonatal lethal murine model of
      mut(0) methylmalonic acidemia.
AB  - Methylmalonic acidemia (MMA), an autosomal recessive metabolic disorder, is most
      often caused by mutations in methylmalonyl-CoA mutase (MUT). Severely affected
      patients typically present with metabolic crisis in the early neonatal period and
      can perish despite intervention. Survivors follow an unstable course and can
      require elective liver transplantation to prevent life-threatening metabolic
      decompensation. Therapeutic alternatives to liver transplantation such as
      hepatocyte-directed gene and cell therapies lack experimental validation. We have
      used a murine model of mut0 MMA to assess the efficacy of virus-mediated gene
      therapy to rescue the neonatal lethality seen in the Mut(-/-) mice. Affected pups
      and control littermates received either intramuscular or intrahepatic injections
      of adenovirus carrying the Mut gene expressed under the control of the
      cytomegalovirus promoter. All of the Mut(-/-) pups injected via the intramuscular
      route perished within the first 48 hr of birth. However, more than 50% of the
      Mut(-/-) pups that received intrahepatic injections survived beyond weaning (day
      15). The treated mutants expressed methylmalonyl-CoA mutase mRNA and protein, and
      displayed decreased metabolite levels compared with uninjected Mut(-/-) mice. The
      results demonstrate that adenovirus-mediated, hepatic methylmalonyl-CoA mutase
      expression can rescue Mut(-/-) pups from neonatal mortality and provide proof-of
      principle evidence for the efficacy of liver-directed gene delivery in
      methylmalonic acidemia.

PMID- 18052794
TI  - Researchers examine contaminants in food, deaths of pets.

PMID- 18052795
TI  - Comments on changes in the veal industry.

PMID- 18052796
TI  - Sea otters in a dirty ocean.
AB  - The connection between the health of humans, animals, and the environments in
      which they live have been well recognized and have recently been referred to as
      one health, one medicine. An example of the interconnectedness of human, animal,
      and ecosystem health is provided by the situation facing southern sea otters off
      the US Pacific coast.

PMID- 18052797
TI  - What is your diagnosis? Sialoliths.

PMID- 18052798
TI  - Responses of dogs to dietary omega-3 fatty acids.
AB  - Long-chain omega-3 fatty acids from fish oil and other marine sources appear to
      be capable of modifying inflammatory and immune responses in dogs. Information is
      provided on the capacity of dogs to metabolize omega-3 fatty acids and the
      effects of omega-3 fatty acids on skin and coat, inflammatory responses, and
      neurologic development in puppies.

PMID- 18052799
TI  - Revenue, expenses, and returns on resources for US veterinary private practices,
      2003 and 2005.
AB  - Median gross practice revenue for all types in 2005 was $669,000, compared with
      $624,904 in 2003. Median total practice expenses were $455,780 in 2005, compared
      with $386,310 in 2003. Both median gross practice revenue and median total
      practice expenses varied widely with practice type.

PMID- 18052800
TI  - Determining the optimal age for gonadectomy of dogs and cats.
AB  - Elective gonadectomy of dogs and cats is one of the most common veterinary
      procedures in the United States. Increasingly, dog owners and members of the
      veterinary profession throughout the world have questioned the optimal age for
      performance of these procedures and whether these procedure should even be
      performed as elective surgeries.

PMID- 18052801
TI  - Detection of Toxoplasma gondii-like oocysts in cat feces and estimates of the
      environmental oocyst burden.
AB  - OBJECTIVE: To estimate the analytic sensitivity of microscopic detection of
      Toxoplasma gondii oocysts and the environmental loading of T gondii oocysts on
      the basis of prevalence of shedding by owned and unowned cats. DESIGN: Cross
      sectional survey. SAMPLE POPULATION: 326 fecal samples from cats. PROCEDURES:
      Fecal samples were collected from cat shelters, veterinary clinics, cat-owning
      households, and outdoor locations and tested via ZnSO(4) fecal flotation.
      RESULTS: Only 3 (0.9%) samples of feces from 326 cats in the Morro Bay area of
      California contained T gondii-like oocysts. On the basis of the estimated tonnage
      of cat feces deposited outdoors in this area, the annual burden in the
      environment was estimated to be 94 to 4,671 oocysts/m(2) (9 to 434
      oocysts/ft(2)). CONCLUSIONS AND CLINICAL RELEVANCE: Despite the low prevalence
      and short duration of T gondii oocyst shedding by cats detected in the present
      and former surveys, the sheer numbers of oocysts shed by cats during initial
      infection could lead to substantial environmental contamination. Veterinarians
      may wish to make cat owners aware of the potential threats to human and wildlife
      health posed by cats permitted to defecate outdoors.

PMID- 18052803
TI  - Evaluation of buffy coat smears for circulating mast cells in healthy cats and
      ill cats without mast cell tumor-related disease.
AB  - OBJECTIVE: To examine buffy coat smears for circulating mast cells in clinically
      normal cats and cats with illnesses unrelated to mast cell tumors and identify
      whether conditions other than mast cell tumors are associated with mastocytemia
      in cats. DESIGN: Prospective study. ANIMALS: 40 clinically normal cats and 40
      cats with diseases unrelated to mast cell tumors (all cats were client owned).
      PROCEDURES: A blood sample for a CBC, serum biochemical analyses, and buffy coat
      evaluation was obtained from each cat. Ill cats underwent other testing on the
      basis of their disease process. RESULTS: No mast cells were detected in any
      sample. Eosinophilia was evident in 11 (27.5%) and 12 (30%) clinically normal and
      ill cats, respectively. Basophilia was identified in 4 (10%) and 8 (20%)
      clinically normal and ill cats, respectively. Eight of the 40 (20%) ill cats had
      neutrophilia. CONCLUSIONS AND CLINICAL RELEVANCE: Circulating mast cells were not
      identified in clinically normal cats or ill cats without mast cell tumor-related
      disease. Ill cats did have conditions that caused eosinophilia, basophilia, or
      neutrophilia. The absence of mast cells in buffy coats obtained from clinically
      normal and ill cats lends support to the current practice of buffy coat
      evaluation for tumor staging and follow-up examinations in cats with mast cell
      tumors. Further studies of buffy coat analysis in cats with different forms of
      mast cell tumors are indicated to specifically elucidate the test's prognostic
      value for those patients.

PMID- 18052804
TI  - Risk factors for excessive tibial plateau angle in large-breed dogs with cranial
      cruciate ligament disease.
AB  - OBJECTIVE: To identify risk factors for development of excessive tibial plateau
      angle (TPA) in large-breed dogs with cranial cruciate ligament disease (CCLD).
      DESIGN: Case-control study. ANIMALS: 58 dogs with excessive TPAs (ie, TPA >or= 35
      degrees ; case dogs) and 58 dogs with normal TPAs (ie, TPA <or= 30 degrees ;
      control dogs). PROCEDURES: Medical records and radiographs were reviewed and
      owners were interviewed to identify potential risk factors for excessive TPA.
      RESULTS: Case dogs were 3 times (95% confidence interval, 1.2 to 8.0) as likely
      to have been neutered before 6 months of age as were control dogs. Case dogs with
      TPA >or= 35 degrees in both limbs were 13.6 times (95% confidence interval, 2.72
      to 68.1) as likely to have been neutered before 6 months of age as were control
      dogs with TPA <or= 30 degrees in both limbs. Case dogs were significantly younger
      at the onset of hind limb lameness than were control dogs. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that early neutering was a significant risk
      factor for development of excessive TPA in large-breed dogs with CCLD. Further
      research into the effects of early neutering on TPA and the pathophysiology of
      CCLD is warranted.

PMID- 18052805
TI  - Use of a titanium mesh for cranioplasty following radical rostrotentorial
      craniectomy to remove an ossifying fibroma in a dog.
AB  - CASE DESCRIPTION: A 6-year-old Australian Terrier was evaluated for surgical
      removal of an ossifying fibroma of the left calvarium of 7 months' duration.
      CLINICAL FINDINGS: Computed tomography revealed invasion of the mass through the
      left parietal bone and extension into the epidural space of the brain. TREATMENT
      AND OUTCOME: A left rostrotentorial and frontal bone craniectomy was performed,
      and the mass was removed, along with a 1-cm margin of grossly normal bone.
      Cranioplasty was performed with a combination of porcine submucosa, titanium
      mesh, and screws. The dog recovered from surgery without complications and was
      discharged 3 days later. The dog was followed up for 24 months after surgery and
      has remained clinically normal. CLINICAL RELEVANCE: Findings suggested that
      rostrotentorial craniectomy is a viable option for removal of benign tumors
      affecting the parietal bones in dogs. Reconstruction of the resulting defect in
      the calvarium is possible with a combination of porcine submucosa and rigid
      titanium mesh.

PMID- 18052806
TI  - Primary and secondary limb cellulitis in horses: 44 cases (2000-2006).
AB  - OBJECTIVE: To determine historical, physical, and microbiologic findings in
      horses with limb cellulitis and identify factors associated with short- and long
      term outcome. DESIGN: Retrospective case series. ANIMALS: 44 horses with limb
      cellulitis. PROCEDURES: Information obtained from medical records included use,
      history, affected limb, diagnostic procedures, treatment, and short-term outcome.
      Long-term follow-up information was obtained by means of a telephone survey.
      RESULTS: Twenty-four horses had primary cellulitis, and 18 of the 24 (75%) had a
      hind limb affected. Results of microbiologic culture were positive for all 20
      horses with primary cellulitis from which specimens were obtained, with coagulase
      positive Staphylococcus spp recovered from 12 of the 20. Short-term survival rate
      was 67% (16/24) for horses with primary cellulitis; 7 of the 9 horses available
      for long-term follow-up were being used for their intended use, and 4 had had a
      recurrence. Results of microbiologic culture were positive for 13 of the 16 (81%)
      horses with secondary cellulitis from which specimens were obtained. Short-term
      survival rate for horses with secondary cellulitis was 90% (18/20). Eleven of the
      17 horses available for long-term follow-up were being used for their intended
      use; 2 had had a recurrence. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that cellulitis can be a life-threatening condition in horses. Horses
      that were febrile at admission or that developed laminitis were significantly
      less likely to survive. The prognosis for return to function was guarded, and
      recurrence was a potential concern.

PMID- 18052808
TI  - Associations between teat injuries and fistula formation in lactating dairy cows
      treated with surgery.
AB  - OBJECTIVE: To determine associations between rate of fistula formation and
      parity, lactation period, wound age, wound location, and shape of teat injuries
      in surgically treated teats in dairy cows. STUDY DESIGN: Prospective clinical
      study. ANIMALS: 106 lactating dairy cows with teat lacerations. PROCEDURES:
      Lacerations were classified via shape, location, and age. Associations between
      potential risk factors and fistula formation were analyzed. Seasonal
      distribution, type of injured teat, parity, and days in lactation were
      determined. RESULTS: Cows with teat injury in their first and second parity had
      4.1 times the odds of fistula formation, compared with cows with parity >or= 3.
      Teats sutured within 48 to 72 hours of injury had 8.3 times the odds of fistula
      formation, compared with teats sutured within the first 24 hours. Cows in early
      lactation stage (first 60 days of lactation) were more susceptible to teat
      injuries. Occurrence of teat injury was greater at the third, fourth, and fifth
      parity. CONCLUSIONS AND CLINICAL RELEVANCE: Season, parity, and lactation period
      were associated with prevalence of teat injury in lactating dairy cows in a range
      system. Neither the type of suture material used nor the suturing technique was
      associated with effects on healing of the operated full-thickness teat wounds.
      Factors such as parity and age of the wound can be associated with delay in the
      healing process, which may result in fistula formation.

PMID- 18052809
TI  - A field study of the effects of a monovalent Leptospira borgpetersenii serovar
      Hardjo strain hardjobovis vaccine administered with oxytetracycline on
      reproductive performance in beef cattle.
AB  - OBJECTIVE: To determine whether vaccination with a monovalent Leptospira
      borgpetersenii serovar Hardjo strain hardjobovis vaccine coupled with parenteral
      long-acting oxytetracycline treatment would improve the reproductive performance
      of beef cows. DESIGN: Randomized controlled field trial. ANIMALS: 1,446 Angus
      cross beef cows in 8 locations. PROCEDURES: Cows were given 2 doses, 4 weeks
      apart, of vaccine (treatment; n=741) or placebo (control; 705). Cows in the
      treatment group were also given a single dose of a long-acting oxytetracycline
      formulation (20 mg/kg [9.1 mg/lb], SC) at the time of booster vaccination. Estrus
      synchronization was performed, followed by fixed-time artificial insemination;
      bulls were introduced 14 days after insemination. Serum and urine samples were
      obtained on a random subset of cows (n=194) for detection of serologic titers and
      leptospiruria, and locations were categorized as positive or negative for
      leptospirosis on the basis of detection of leptospiruric cows. RESULTS: No
      differences in pregnancy and calving rates between treatment and control groups
      were detected. Pregnancy rate following artificial insemination was lower among
      cows in locations positive for leptospirosis than among cows in locations
      negative for leptospirosis; however, overall pregnancy rate, calving rate
      following artificial insemination, and overall calving rate did not differ
      between groups when cows were grouped on the basis of location leptospirosis
      status. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that under the
      conditions of the present study, administration of a monovalent Leptospira
      vaccine in conjunction with systemic administration of oxytetracycline did not
      significantly improve reproductive performance of beef cows.

PMID- 18052810
TI  - An outbreak of dictyocaulosis in lactating cows on a dairy farm.
AB  - CASE DESCRIPTION: The owner of a herd of 74 Holstein-Friesian cattle reported
      decreased milk production, weight loss, and coughing among lactating cows. Owner
      initiated antimicrobial treatment was unsuccessful; 1 lactating cow died, and 50%
      of the lactating cows had clinical signs of respiratory distress, such as
      tachypnea and coughing. CLINICAL FINDINGS: On the basis of history, physical
      examination findings, and fecal examination results, affected animals were
      determined to have Dictyocaulus viviparus (lungworm) infestation. The disease
      history suggested that the herd contained cows with subclinical patent lungworm
      infestations; after introduction of susceptible heifers, the pastures had become
      heavily infested with D viviparus and clinical problems subsequently developed in
      both newly introduced and resident cows. TREATMENT AND OUTCOME: Affected and
      unaffected heifers and adult cows were treated with a pour-on formulation of
      eprinomectin (0.5 mg/kg [0.23 mg/lb]). One animal died, but 2 weeks after
      treatment, clinical signs among affected cattle were markedly improved. Ten weeks
      after treatment, milk production improved from 23 kg/cow/d (51 lb/cow/d) to 28
      kg/cow/d (62 lb/cow/d). CLINICAL RELEVANCE: The outbreak provides additional
      evidence that dictyocaulosis is becoming more common among adult dairy cattle,
      rather than almost exclusively affecting young stock. This may be attributable to
      anthelmintic use and management practices on dairy farms. Combined with anecdotal
      reports of an increase in the incidence of dictyocaulosis among adult cattle in
      North America, D viviparus infestation should be included as a differential
      diagnosis for decreased milk production, weight loss, and coughing among adult
      dairy cattle.

PMID- 18052811
TI  - Zoonoses associated with petting farms and open zoos.
AB  - The popularity of open farms and petting zoos has increased markedly over the
      last 5 years, with most children in developed countries now having the
      opportunity to visit such a facility at some stage in their childhood, either
      through school or family visits. The open access policy of these establishments
      allows visitors to be in direct contact with animals such as sheep (lambs),
      goats, cats (kittens), dogs (puppies), and birds and to have the opportunity to
      feed such animals. This contact may lead to the transmission of microbial
      pathogens from animals to humans, e.g., Escherichia coli O157:H7, resulting in
      human disease. This review outlines the causal organisms associated with such
      zoonoses, a description of previous outbreaks at farms and zoos, as well as
      infection control measures to help prevent such zoonotic infections.

PMID- 18052813
TI  - Situating end-of-life decision making in a hybrid ethical frame.
AB  - Good communication in EOL (end-of-life) discussions is described at a general
      level in the literature, but there are few studies of EOL discussions at the
      level of interaction, with data drawn from the actual talk between physicians and
      families. In this article I present a discourse analysis of EOL discussions from
      an American ICU (intensive care unit) where the decision to withdraw life support
      is situated in a hybrid ethical frame co-constructed as the final phase of the
      EOL discussion. In Mishler's (1984) terms, the final phase of the EOL discussion
      merges the voice of medicine and the voice of the lifeworld, with both physicians
      and families initiating, developing, and repeating particular topics that
      encompass not only the logistics of death but also the ethics of the end-of-life
      decision. Physicians index their ethical accountability in terms of medical
      futility, and families express their accountability in terms of an ethics of
      consciousness. The hybrid ethical frame that is co-constructed ultimately centers
      upon consensus that the 'right' decision has been made from both ethical
      perspectives.

PMID- 18052814
TI  - Professional-patient communication in the treatment of mental illness: a review.
AB  - The quality of the professional-patient relationship in the treatment of mental
      illness predicts patient outcome. Hence, we conducted a review of recorded
      professional-patient communication to identify existing research, methods, and
      findings. Sixteen studies focused on (i) how psychiatric symptoms are manifested
      in patient communication; (ii) the role of therapist communication in patient
      improvement; (iii) the influence of sociodemographic characteristics on doctor
      patient communication; and (iv) how patients and professionals jointly construct
      therapeutic interactions. The findings were disparate and included (a) patient
      nonverbal communication is impaired in depression and schizophrenia; (b) the use
      of specific therapeutic skills led to improvement in depression; high expressed
      emotion (criticism and emotional over-involvement) in treating schizophrenia was
      a state rather than trait characteristic of therapists; (c) patient gender,
      income, and education influenced communication about depression, anxiety, and
      medication; and (d) psychiatrists' varying institutional agendas, which sometimes
      competed with patients' agendas, strongly shaped their consultations. Few studies
      investigated two-way professional-patient communication, with most focusing on
      either patient or therapist communication in isolation from the other. Finally,
      methodological advances in linking communication processes with treatment
      outcomes in large-scale observational studies and trials are a challenge for
      research on medical communication.

PMID- 18052815
TI  - Community as a key to healing after the death of a child.
AB  - Communication is believed to hold a central role in recreating an individual's
      sense of meaning and well-being after a loss. Narrative theory in particular
      points to ways that people create meaning and connection with others. Literature
      on bereavement suggests that the formation of connections with others, or
      building community, comprises an important part of the healing process. For this
      study, the content of bulletin board postings commemorating deceased children was
      studied quantitatively and qualitatively. Data were examined to learn how
      contributors used the Web site to connect with others who shared experience of
      losing a child, engage in meaningful shared activities, and create community.
      Findings from the data analysis suggest that the Web site contributors are able
      to discuss topics that might be restricted in other communication scenes. The
      discussion of these topics allows them to serve as 'witnesses' to truths learned
      as a result of the loss of a child and enables the participants to keep the
      memory of the child alive. By participating in this scene of meaning negotiation,
      we argue that the participants actively construct a counterplot to societal
      narrative expectations for bereavement that facilitates the creation of some
      positive meanings.

PMID- 18052816
TI  - Whiteboards: mediating professional tensions in clinical practice.
AB  - In this paper we argue that whiteboards in clinical settings play a hybrid role:
      communicating inter- and intraprofessional directives, mediating professional
      tensions, and mitigating potentially face-threatening acts. The data upon which
      this paper is based emanate from two independently conducted ethnographic
      studies: the first explored a range of nurse-nurse and nurse-doctor communication
      practices in operating rooms, while the second explored work routines and
      communication methods in oncology wards. Data collection included fieldwork using
      observations, interviews assisted by photographic methods, and in the first
      study, a personal diary. A deconstructive analysis was independently undertaken.
      As a communication method, the use of whiteboards in clinical settings provided a
      focal point for the coordination of clinical work activities and for the
      dissemination of information to large groups of people. Whiteboards were a
      conduit for potentially face-threatening information in that they facilitated the
      policing and disciplining of staff, while distancing communicators from one
      another. We conclude that whiteboards are 'pseudo-synchronous' in nature,
      enabling 'communication at a distance'. In doing so, whiteboards may facilitate
      and economize clinical communication but they also perpetuate the invisibility of
      nurses' contribution to ensuring safe care, and they mask the symbolic violence
      that is committed within and between health professionals.

PMID- 18052817
TI  - Negotiating frame ambiguity: a study of simulated encounters in medical
      education.
AB  - We report an investigation of the sociolinguistic characteristics of simulated
      encounters (role plays) in medical education, focusing in particular on frame
      negotiation. The role played by context in influencing the nature of out-of-frame
      activity is noted through comparison with another published study of simulations
      (Linell and Thunqvist 2003). While in general sustaining a role-playing frame
      that involved an orientation to exact mimicry of clinical situations, the
      interactional work done to sustain this appearance of 'authenticity' at certain
      moments was revealed by out-of-frame utterances. One participating doctor in
      particular used humor to exploit the ambiguous realism of the role-playing frame.
      The success of this doctor in acquiring and applying new communication behaviors
      problematizes the view that 'realism', achieved through mimicry, is solely
      responsible for the success of training interventions. The implications for
      studying other kinds of simulated encounters, including an outline for a program
      of research into the sociolinguistics of acting tasks in general, are outlined.
      Sociolinguistic researchers involved in observational studies of talk would
      benefit from adopting the view that role-played, rehearsed, and even scripted
      talk of the sort used in dramatic performance is a variety of naturally occurring
      data and therefore worthy of study.

PMID- 18052818
TI  - Lexical conflation and edible iconicity: two sources of ambiguity in American
      vernacular health terminology.
AB  - Examination of lexical items in naturally occurring vernacular prose shows
      patterns of ambiguities in how Americans discuss health issues. Samples from the
      Freiburg-Brown corpus of American English and varied registers of popular health
      writing found online reveal two principles of naming beliefs that crosscut the
      uses of many ambiguous terms: the semantic principle of 'lexical conflation' and
      the semiotic principle of 'edible iconicity'. Both are shown to reflect sources
      of nutritional conceptualizations. Lexical conflation is illustrated by uses of
      fat, cholesterol, sugar, oil, and germ, with modifiers shown to help disambiguate
      terms. Edible iconicity, where meaning is attached to the visible form of what is
      ingested and characteristics of a food are believed to transfer to the person who
      eats it, is illustrated through aspects of hard, white, and hot. Applications are
      suggested that take into account the influence on nutritional choices that can
      occur when lay people misinterpret specialized information as signifying a
      nonspecialist sense. Recognition of these two principles has the potential to
      affect public health policy by helping practitioners to identify and modify
      ambiguous words, and to take into account tendencies to interpret metaphors
      literally, especially regarding iconic ingredients and their presumed effect upon
      the body.

PMID- 18052820
TI  - The national disaster medical system: past, present, and suggestions for the
      future.
AB  - This article reviews the history and structure of the National Disaster Medical
      System (NDMS), with an emphasis on its definitive care component. NDMS's capacity
      to handle very large mass casualty events, such as those included in the National
      Planning Scenarios, is examined. Following Hurricane Katrina, Congress called for
      a reevaluation of NDMS. In that context, we make three key suggestions to improve
      NDMS's capacity to respond to large mass casualty disasters: (1) increase the
      level of engagement by the private (i.e., nonfederal) healthcare system in
      preparedness and response efforts; (2) increase the reliance on regional hospital
      collaborative networks as part of the backbone of the NDMS system; and (3)
      develop additional, alternative patient transportation systems, linked to the
      overall NDMS patient tracking effort, to decrease the sole reliance on DoD long
      haul air transport in medical evacuation.

PMID- 18052821
TI  - Tubeless percutaneous nephrolithotomy: 5 years of experience in 201 patients.
AB  - BACKGROUND AND PURPOSE: Our aim was to evaluate the safety, effectiveness, and
      feasibility of tubeless percutaneous nephrolithotomy (PCNL). PATIENTS AND
      METHODS: From June 2000 to September 2005, 201 patients with renal stones >2 cm
      underwent tubeless PCNL by a single surgeon. We report details of the outcomes.
      RESULTS: The complete stone clearance rate was 91.04% (183 patients). After
      surgery, 18 patients (8.96%) had stones (mean size = 7 mm) detected on a plain
      abdominal radiograph or ultrasonographic examination and were referred for
      shockwave lithotripsy. The mean stone size was 30 mm (range 20-40 mm). The mean
      operative time was 35 minutes (range 30-60 min), and the mean hospital stay was
      3.5 days (range 2-5 days). Postoperative ultrasonography did not reveal
      considerable fluid collection. There were no visceral injuries. Twenty-two
      (10.9%) patients received a transfusion, and 16 (7.9%) patients had urinary tract
      infection. CONCLUSION: In our experience, tubeless PCNL is safe, effective, and
      feasible without any discomfort for patients.

PMID- 18052822
TI  - Percutaneous nephrolithotomy in the supine position: a neglected approach?
AB  - PURPOSE: The aim of the study was to demonstrate the safety and effectiveness of
      single-stage percutaneous nephrolithotomy performed in the supine position.
      PATIENTS AND METHODS: A single surgeon performed 322 consecutive percutaneous
      nephrolithotomies in patients in the supine position between 1999 and 2006, which
      were studied prospectively. RESULTS: There were no complications related to the
      supine position, and in only one patient was there failed access. This patient's
      kidney was subsequently punctured with the patient in the supine position. There
      were no colonic injuries, no pneumothoraces, and a transfusion rate of 3.7%.
      Surgery on all patients with stones, including staghorn calculi and bilateral
      stones managed synchronously, was in the supine position. The median time to
      percutaneous access in a timed cohort of 27 patients was 5 minutes. The stone
      clearance rate was 91%. The median length of hospital stay was reduced from 6
      days in the initial unstented patients to 3 days in the study overall when most
      patients received stents. CONCLUSIONS: Percutaneous nephrolithotomy in the supine
      position is safe, effective, and suitable for the majority of patients. It offers
      the potential advantages of better urethral access, less patient handling, and
      the need to only drape once, thus reducing the overall operative time compared to
      the traditional prone position.

PMID- 18052823
TI  - Strategic directions in tissue engineering.
AB  - The field of tissue engineering is developing rapidly. Given its ultimate
      importance to clinical care, the time is appropriate to assess the field's
      strategic directions to optimize research and development activities. To
      characterize strategic directions in tissue engineering, a distant but reachable
      clinical goal was proposed and a worldwide body of 24 leaders in tissue
      engineering was queried systematically to determine the best paths toward that
      goal. Using a modified Hoshin process, we identified 14 critical activity
      categories and then stratified them by their immediate priority for the field.
      The result of the analysis illustrates a highly interdependent set of activities
      that are dominated by the need for an understanding of angiogenesis, stem cell
      science, and the utilization of molecular biology and systems biology tools to
      enable a deeper comprehension of tissue development and control.

PMID- 18052824
TI  - The opposing effects of lipopolysaccharide on the antitumor therapeutic efficacy
      of DNA vaccine.
AB  - DNA vaccine represents a novel method to elicit immunity against infectious
      disease. Lipopolysaccharide (LPS) copurified with plasmid DNA may affect
      therapeutic efficacy and immunological response. We aimed to study the effect of
      LPS on the therapeutic efficacy of HER-2/neu DNA vaccine in a mouse tumor animal
      model. Plasmid DNA purified from commercial EndoFree plasmid purification kits
      functioned as a better therapeutic DNA vaccine than that purified from Non
      EndoFree purification kit, which contains >or=0.5 microg LPS per 100 mg DNA
      plasmid. To further investigate the effect of LPS on the therapeutic efficacy of
      DNA vaccine, increasing amount of LPS was added to endotoxin-free plasmid DNA,
      and inoculated on mice with established tumors. One mug of LPS significantly
      attenuated the therapeutic effect of neu DNA vaccine and increased Th2 immune
      responses bias with interleukin-4 cytokine production. In contrast, high amount
      (100 microg) of LPS enhanced the therapeutic efficacy of neu DNA vaccine with an
      increase of cytotoxic T lymphocyte response and Th1 immune response. The effect
      of LPS on DNA vaccine was diminished when the tumor was grown in toll-like
      receptor 4 (TLR4)-mutant C3H/HeJ mice. Our results indicate that variation in the
      LPS doses exerts opposing effects on the therapeutic efficacy of DNA vaccine, and
      the observed effect is TLR4 dependent.

PMID- 18052825
TI  - A novel splicing variant of proprotein convertase subtilisin/kexin type 9.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the most recently
      identified member of the proprotein convertase family. Genetic and cell biology
      studies have suggested a critical role of PCSK9 in regulating low-density
      lipoprotein receptor (LDLR) protein levels and thus modulating plasma LDL
      cholesterol. Recent data on the molecular basis for PCSK9 action support the
      model in which PCSK9 is self-cleaved, secreted, and tightly bound to the EGF-A
      repeat of LDLR extracellular domain. PCSK9 binding to LDLR is essential for the
      ensuing receptor-mediated endocytosis and is speculated to lock LDLR in a
      specific conformation that favors degradation in lysosomal compartment instead of
      recycling back to plasma membrane. We report here a novel human PCSK9 splicing
      variant, which we named PCSK9sv. PCSK9sv had an in-frame deletion of the eighth
      exon of 58 amino acids and was expressed in multiple tissues, including liver,
      small intestine, prostate, uterus, brain, and adipose tissue. Unlike wild-type
      PCSK9, which is secreted, PCSK9sv expressed in human embryonic kidney HEK293
      cells failed to process the prosegment intracellularly and thus was not secreted
      into the medium. Examination of potential functions revealed that PCSK9sv did not
      change the LDLR protein levels. Two mutations that have been reported in humans
      with the associated changes in plasma LDL cholesterol were within exon 8, and
      thus the expression and function of the two mutants were studied. Both N425S and
      A443T mutants were processed normally, secreted, and reduced LDLR levels.
      However, the physiological function of this novel splicing variant of PCSK9 has
      yet to be determined.

PMID- 18052831
TI  - The Istanbul international consensus statement on the perinatal care of multiple
      pregnancy.
AB  - The purpose of this document is to expand the 1995 ISTS/COMBO Declaration of
      Rights which was initially produced to promote awareness of the special needs of
      multiple birth infants, children, and adults. It addresses the clinical and
      ethical dimensions of perinatal care of multiple pregnancy. The ad hoc committee
      was chaired by Isaac Blickstein. The following individuals were present (in
      alphabetical order): Birgit Arabin (Zwolle, Netherlands/Berlin, Germany), Isaac
      Blickstein (Rehovot, Israel), Frank A. Chervenak (NY, USA), Zehra Nese Kavak
      (Istanbul, Turkey), Louis G. Keith (Chicago, USA), Eric S. Shinwell (Rehovot,
      Israel) and Yves Ville (Paris, France). Secretary of the meeting was Alin Basgul
      (Istanbul, Turkey). This statement was endorsed by the International Society of
      Twin Studies (Ghent, Belgium, June, 2007) and by the World Association of
      Perinatal Medicine (Florence, Italy, September, 2007).

PMID- 18052832
TI  - Uterine activity monitoring during labor.
AB  - AIM: To summarize the currently available knowledge on (1) the methods to monitor
      uterine activity (UA); (2) the units to quantify UA; and (3) to assess the
      importance of abnormal contraction patterns on the condition of the fetus. The
      need for correct assessment and interpretation of the uterine contraction curve
      to improve fetal outcome will be emphasized. STUDY RESULTS: Correct assessment of
      the uterine contraction curve is an essential part of the cardiotocogram and
      should be obtained by the best method available; i.e., internal tocography (IT).
      IT provides objective information on quantization of UA and has the ability to
      obtain a good quality trace in an obese, restless patient. Accurate information
      on UA is essential because elevated UA during the first and second stage of labor
      can increase the risk of adverse fetal outcome. The relaxation time appears to be
      an important contraction parameter to maintain fetal well-being during labor.
      Almost all abnormal contraction patterns are characterized by shortening of the
      relaxation time and can lead to severe asphyxia. Duration, amplitude and
      frequency of contractions are of importance as well. The mean active pressure
      unit is the means to quantify UA since it incorporates these three contraction
      parameters. CONCLUSION: Proper application of UA monitoring by means of the
      internal method and adequate reading and interpretation of the uterine
      contraction curve is a prerequisite for high quality electronic fetal heart rate
      monitoring.

PMID- 18052833
TI  - Is non-directive counseling for patient choice cesarean delivery ethically
      justified?
AB  - The current controversy concerning patient choice cesarean delivery potentially
      affects all women of child-bearing age and the physicians who care for them. The
      purpose of this paper is to address three salient issues within the patient
      choice cesarean delivery controversy. First, is performing patient choice
      cesarean delivery consistent with good professional medical practice? Second, how
      should physicians respond to or counsel patients who request patient choice
      cesarean delivery? And, third, should patient choice cesarean delivery be
      routinely offered to all pregnant women?

PMID- 18052834
TI  - GDM women in good glycemic control: which meal-related measure enhances fetal
      well-being?
AB  - OBJECTIVE: To determine which meal-related glucose measure maximizes perinatal
      outcome in gestational diabetes mellitus (GDM) women who have achieved
      established levels of glycemic control. METHODS: Two thousand two hundred and
      ninety-eight GDM women were stratified by meal-related blood glucose measures:
      fasting (<95 mg/dL); pre-meal (< or =90 mg/dL); 2-h post-meal (< or =120 mg/dL);
      mean (< or =100 mg/dL). The rates of unidentified adverse outcome for composite
      outcome, neonatal intensive care unit (NICU), metabolic and respiratory
      complications and cesarean section delivery within each meal-related glucose
      threshold were calculated. RESULTS: Overall, 25-69% of large-for-gestational-age
      (LGA)/macrosomic infants were not identified within the recommended meal-related
      glucose threshold measurements. The lowest rates of unidentified morbidity were
      found in the pre-meal and mean blood glucose categories while the highest rates
      were in the post-meal category despite subjects achieving recommended levels of
      glycemic control. The increased rate of LGA/macrosomia within 10 mg/dL increments
      for each meal-related glucose category revealed that regardless of the meal
      related category, the rate of LGA was significantly higher (15-25%). Logistic
      regressions (dependent variable= composite outcome or LGA) showed that mean blood
      glucose was the only significant contributor. CONCLUSION: Currently recommended
      meal-related glucose measures do not preclude adverse fetal outcome.

PMID- 18052835
TI  - Intrahepatic cholestasis of pregnancy: detection with urinary bile acid assays.
AB  - AIMS: To determine sensitivity and specificity of urine bile acid sulfate (UBAS)
      and non-sulfated urine bile acid (UBA) assays for detection of intrahepatic
      cholestasis of pregnancy (ICP). METHODS: Urine was collected prospectively from
      healthy and pruritic patients evaluated for ICP. Results were expressed as a
      ratio to urinary creatinine. RESULTS: Of 20 patients evaluated for ICP, 14 had
      confirmed ICP by serum testing and six had pruritus only. UBAS results were
      higher with ICP (P<0.001) and increased with gestational age in healthy controls.
      Adjusted for gestational age, the multiples of the median (MoM) were still higher
      (2.64+/-1.11, 1.05+/-0.54, P<0.001). The sensitivity was 100% and specificity 83%
      at 1.5 MoM in pruritic patients. UBA results were higher with ICP (23.0+/-9.8,
      12.8+/-7.4, P<0.001), with sensitivity of 100% and specificity of 50% at 10.2
      micromol/g cretinine. CONCLUSION: Urinary bile acids can detect or exclude ICP
      with serum abnormalities. Urine bile acid sulfates have higher specificity than
      non-sulfated urine bile acids at equivalent sensitivities, but co-detection of
      progestin sulfates is suspected.

PMID- 18052836
TI  - Elevated blood lead levels in pregnant women: identification of a high-risk
      population and interventions.
AB  - There has been a significant decrease in the number of preschool children with
      elevated blood lead levels (BLL), from 88.2 to 4.4 per 10,000 children over the
      last three decades as shown by National Health and Nutritional Examination Survey
      (NHANES) data. However, there are still certain high-risk populations that have
      not been well studied. One such group is that of pregnant women. During
      pregnancy, BLL tends to increase due to greater bone turnover, which causes
      release of lead stored in bone. This increase may not affect the pregnant woman's
      health directly but could be extremely harmful to the rapidly developing central
      nervous system in the fetus as it crosses the placenta easily. This current study
      was undertaken to estimate the prevalence of elevated BLL in pregnant women in a
      community hospital, monitor the effect of routine preventive practices on
      maternal BLL, and to elucidate the relationship between maternal and neonatal BLL
      and their anthropometric indices. A retrospective chart review was conducted on
      all hospital deliveries occurring in the first six years after the initiation of
      universal blood lead screening of pregnant women (n=6880). The prevalence of
      elevated lead (> or =10 microg/dL) in our patient population was 1.7%. The
      factors associated with elevated lead levels were recent immigration to the US,
      poor socioeconomic status and low educational levels. Simple interventions such
      as hand washing as well as calcium and iron supplementation significantly reduced
      maternal BLL from 16.82+/-9.5 to 11.48+/-9.3 microg/dL (P<0.0001). A significant
      correlation (r=0.4, P<0.007) is present between the post-intervention but not the
      pre-intervention maternal BLL and the neonatal BLL. Given the vulnerability of
      the developing fetal brain and that CNS complications are associated with
      elevated lead levels, antenatal lead screening should be part of routine prenatal
      care. Simple preventive measures may play a role in decreasing maternal BLL and
      thereby decreasing transplacental transfer of lead to the fetus.

PMID- 18052837
TI  - Correlation of transthoracic echocardiography and right heart catheterization in
      pregnancy.
AB  - OBJECTIVES: To correlate estimated pulmonary artery pressures (PAP) by
      echocardiography with right heart catheterization (RHC) measurements and to
      correlate estimated left ventricular ejection fraction (EF) by echocardiography
      with cardiac output (CO) measurements by RHC. STUDY DESIGN: All women who had
      echocardiography at a single institution during a 6-year period and underwent RHC
      during pregnancy were included. Echocardiography estimates of right ventricular
      systolic pressure (RVSP) and EF were correlated with measured RHC PAP and CO,
      respectively. RESULTS: Eighteen patients underwent 21 RHCs, 10 antepartum at the
      catheterization laboratory and the remaining 11 intrapartum, performed with the
      use of a pulmonary artery catheter placed prior to the onset or induction of
      labor. Correlation between RVSP and PAP was good (rho=0.79, P<0.0001);
      nonetheless, in 30% of cases RHC eliminated the concern for pulmonary
      hypertension (PHTN). There was minimal correlation between EF and CO. CONCLUSION:
      Despite good statistical correlation between echocardiography and RHC for
      determining pulmonary artery pressure, RHC should be considered for major
      decisions such as pregnancy interruption or preterm delivery given the proportion
      of cases where concern for PHTN was excluded by RHC. EF provides a poor proxy for
      CO.

PMID- 18052838
TI  - Impact of the new French clinical practice recommendations in embolization in
      postpartum and post-abortion hemorrhage: study of 48 cases.
AB  - AIM: To evaluate the use of arterial embolization in postpartum hemorrhage (PPH)
      by comparing the indications, efficacy, times to diagnosis, treatment, and
      embolization, and conditions of management of patients before and after
      publication of the College National des Gynecologues et Obstetriciens Francais
      clinical practice recommendations (CPR). METHODS: Forty-eight patients who
      underwent embolization between January 2000 and December 2005 were included in a
      retrospective, descriptive, and comparative study. We compared the management
      before (n=21) and after (n=27) publication of the CPR. The main outcome measures
      were time to diagnosis of PPH, time to treatment initiation, time to decision to
      implement embolization, time to embolization, hemodynamic characteristics.
      RESULTS: The number of embolizations has quadrupled since publication of the CPR,
      and the time taken to decide on embolization has been reduced by 30%. The success
      rate was 96%, there were no second embolization procedures, and one complication
      was recorded (hematoma of pubic symphysis). Hemodynamic status was better in
      patients treated after the CPR (P=0.003). CONCLUSION: Embolization is an
      effective and safe technique, with a low complication rate. In our healthcare
      network, the decision to use embolization was faster since the CPR, embolizations
      have quadrupled, and patients' hemodynamic status has improved.

PMID- 18052839
TI  - The relationship between congenital malformations and preterm birth.
AB  - AIMS: To investigate how congenital malformations (CM) are associated with
      preterm (PT) births. METHODS: A population cohort study analyzed data from the
      New York State Congenital Malformations Registry to look at live births from the
      Lower Hudson Valley Region from 2000-2003. ICD9 codes identified all cases and
      types of CM in addition to cases with multiple malformations. Subjects were
      categorized into one of three gestational age (GA) groups. Only cases with a
      known GA at birth were included. Poisson regression analysis established a risk
      ratio for children born with a CM of being born preterm. RESULTS: The PT birth
      rate was 11.2% and the CM rate 3%. Children with a CM were more likely to be born
      PT (RR: 2.20; CI: 2.01-2.40), moderately preterm (RR: 1.95; CI: 1.76-2.15), and
      very preterm (RR: 3.45; CI: 2.95-4.04) than term. This relationship was
      maintained for most organ systems and malformation types evaluated when checked
      individually. Being born with more than one CM increased the likelihood of being
      born PT (OR: 1.72; CI: 1.37-2.15). CONCLUSIONS: Congenital malformations in
      children have a significant impact upon the likelihood of being born PT, and
      contribute significantly to the degree of prematurity.

PMID- 18052840
TI  - Obstetrical factors for death and brain injury among extremely-low-birth-weight
      infants.
AB  - OBJECTIVE: To examine the obstetrical risk factors for death and brain injury
      among extremely-low-birth-weight (ELBW) infants (birth weight <1000 g). STUDY
      DESIGN: Study subjects were 121 ELBW infants born at a single tertiary perinatal
      center. Death among ELBW infants was considered to have occurred when subjects
      died within their corrected age of 40 weeks. In the sub-analysis of the 91 ELBW
      infants who survived their corrected age of 40 weeks, brain injury was defined as
      present when criteria based on ultrasound and/or MRI were substantiated. RESULTS:
      A birth weight of <800 g [adjusted odds ratio (OR), 14.57; 95% confidence
      interval (CI), 4.72-56.98], a younger gestational age of <26 weeks (adjusted OR,
      4.64; 95% CI, 1.60-14.90), and a low Apgar score of <5 (adjusted OR, 3.88; 95%
      CI, 1.32-12.45) were significantly associated with death among ELBW infants. A
      maternal age of 30 years or older (adjusted OR, 3.71; 95% CI, 1.19-13.35) was
      only associated with brain injury among surviving ELBW infants. CONCLUSION:
      Obstetrical care should be aimed at preventing or predicting premature delivery
      especially at <26 weeks of gestation.

PMID- 18052841
TI  - Early detection of a congenital coronary artery fistula in a neonate by Doppler
      color flow mapping.
AB  - AIMS: To describe a case of a congenital coronary artery fistula in a neonate
      with the diagnostic and surgical modalities used to manage this condition. A full
      term infant was recently diagnosed with a coronary artery fistula. The patient
      was a term neonate, born without complications, which then appeared to be
      cyanotic and had a significant heart murmur. RESULTS: Echocardiography
      demonstrated a large right coronary fistula measuring 7 mm in diameter entering
      the right ventricle and a small patent ductus arteriosus (PDA) with a left to
      right shunt. The patient subsequently had patch closure of the coronary artery
      fistula and ligation of the PDA. Recovery followed from the procedure without
      apparent intra-operative or post-operative complications. CONCLUSION: Prompt
      diagnosis and surgical management of the neonate with a coronary fistula is
      essential to reduce the morbidity and mortality that may result from this
      condition.

PMID- 18052842
TI  - The exit procedure (ex-utero intrapartum treatment): management of giant fetal
      cervical teratoma.
AB  - The prognosis of giant cervical teratomas is determined by the severity of the
      associated airway obstruction. Ex-utero intrapartum treatment (EXIT) is a
      technique to establish a patent airway before completion of birth, while the
      infant remains on placental support. We present two cases of newborns with
      cervical teratomas treated with the EXIT procedure. In the first, this technique
      allowed a tracheotomy to be performed, and in the second, correction of tracheal
      displacement and subsequent nasotracheal intubation was achieved.

PMID- 18052843
TI  - Intestinal trefoil factor in treatment of neonatal necrotizing enterocolitis in
      the rat model.

PMID- 18052847
TI  - Development of in vitro methods to predict induction of CYP1A2 and CYP3A4 in
      humans.
AB  - The important role of cytochrome P450 (CYP) drug-metabolizing enzymes has been
      studied for many years, and the potential liabilities of inducing these enzymes
      are well understood. Though several mechanisms of induction have been studied, a
      growing consensus is developing that the aryl hydrocarbon receptor (AHR) and the
      pregnane X receptor (PXR) have evolved as the primary mechanisms responsible for
      clinically relevant drug-drug interactions caused by induction of drug
      metabolizing factors. AHR and PXR have been identified as inducers of a variety
      of Phase I and Phase II drug-metabolizing enzymes, drug transporters, and other
      factors involved in drug metabolism. Though many genes are induced through these
      regulating factors, CYP1A2 and CYP3A4 have been the most reliable biomarkers to
      identify compounds with potential induction liabilities through AHR and PXR,
      respectively. Here are presented several in vitro methods to detect AHR- and PXR
      mediated induction of CYP1A2 and CYP3A4 in fresh and cryopreserved primary human
      hepatocytes, stable transfectants, and transiently transfected immortalized
      cells.

PMID- 18052848
TI  - A three-stage experimental strategy to evaluate and validate an interplate IC50
      format.
AB  - The serial dilution of compounds to establish potency against target enzymes or
      receptors can at times be a rate-limiting step in project progression. We have
      investigated the possibility of running 50% inhibitory concentration experiments
      in an interplate format, with dose ranges constructed across plates. The
      advantages associated with this format include a faster reformatting time for the
      compounds while also increasing the number of doses that can be potentially
      generated. These two factors, in particular, would lend themselves to a higher
      throughput and more timely testing of compounds, while also maximizing chances to
      capture fully developed dose-response curves. The key objective from this work
      was to establish a strategy to assess the feasibility of an interplate format to
      ensure that the quality of data generated would be equivalent to historical
      formats used. A three-stage approach was adopted to assess and validate running
      an assay in an interplate format, compared to an intraplate format. Although the
      three-stage strategy was tested with two different assay formats, it would be
      necessary to investigate the feasibility for other assay types. The
      recommendation is that the three-stage experimental strategy defined here is used
      to assess feasibility of other assay formats used.

PMID- 18052850
TI  - A beta-lactamase reporter assay for monitoring the activation of the smoothened
      pathway.
AB  - The seven-transmembrane protein Smoothened (Smo) mediates the cellular response
      to the Hedgehog protein signal and is involved in cell growth and differentiation
      during embryonic development. Stimulation of the Smo pathway is directly
      implicated in tissue maintenance and repair, but overactivation of Smo could lead
      to tumorigenesis. We developed a robust and sensitive functional cell-based assay
      that measures the activity of endogenous Smo using a beta-lactamase
      transcriptional readout. This is the first Smo reporter assay that utilizes beta
      lactamase reporter technology. This assay type has distinct advantages over other
      reporter technologies and can be used in a high-throughput mode to search for
      therapeutically relevant downstream Smo target effectors.

PMID- 18052851
TI  - LRET-based HTS of a small-compound library for inhibitors of bacterial RNA
      polymerase.
AB  - Resistance mechanisms against whole classes of antibiotics are currently
      developing faster than research generates new structurally different biologically
      active agents. The demand for new antimicrobial drugs has not been matched by the
      speed of discovery. The interface between sigma and core of bacterial RNA
      polymerase offers an attractive target for drug discovery, and we have previously
      described the development of a very robust high-throughput assay for this target
      based on luminescence resonance energy transfer. Here we describe a semiautomated
      screen of a commercially available library (Chembridge, San Diego, CA) that led
      to the identification of four small molecules, two of which have activity in
      preventing in vitro transcription and growth of Escherichia coli.

PMID- 18052852
TI  - Self-regulation and physical activity: the relationship in older adults.
AB  - OBJECTIVES: To examine the relationship between self-regulation and physical
      activity (PA) in older adults. METHODS: A convenience sample (N=284) of older
      adults (M age=70.4 years) was surveyed. RESULTS: Multivariate analyses
      controlling for self-efficacy and socio-demographic variables revealed that using
      self-regulatory strategies more extensively, being male, and having better self
      report health were significantly related to greater PA engagement. Supportive of
      a social cognitive perspective, results were also consistent with mediation,
      where self-regulation partially mediated the relationship between self-efficacy
      and PA. CONCLUSIONS: Further examination of these relationships using prospective
      and experimental designs is recommended. Practical implications of these findings
      are discussed.

PMID- 18052853
TI  - Breast-feeding intentions among low-income pregnant and lactating women.
AB  - OBJECTIVES: Provide a better understanding of the process used by low-income
      pregnant/postpartum women when deciding whether to breast-feed or not. METHODS:
      Pregnant/postpartum women admitted to an obstetrics floor completed a survey to
      determine breast-feeding intention (n=88). RESULTS: Subjects were primarily
      Hispanic and African American women. Beliefs and referent other were related
      positively to attitude and subjective norm, respectively. Subjective norm was
      related positively to intention to breast-feed. Breast-feeding knowledge was low.
      CONCLUSIONS: Others' opinions clearly influence feeding intentions among this
      population of low-income women. Inclusion of these significant others, family,
      and friends within the breast-feeding education process is warranted.

PMID- 18052854
TI  - Smoking cessation counseling as a teachable moment for skin cancer prevention:
      pilot studies.
AB  - OBJECTIVE: To conduct pilot research examining smoking cessation counseling as a
      teachable moment for skin cancer prevention. METHODS: Study I surveyed 199
      beachgoers regarding skin cancer protection. Study II compared a standard smoking
      cessation treatment against one that incorporated skin cancer education (N=35).
      RESULTS: In Study I, smokers were less likely than nonsmokers to wear sunscreen
      or perform skin self-examinations. In Study II, participants were satisfied with
      the integrated program; smoking cessation treatment efficacy was not compromised;
      and skin cancer knowledge and self-efficacy increased. CONCLUSIONS: Further study
      of smoking cessation as a teachable moment for other health behavior change is
      warranted.

PMID- 18052855
TI  - Outcomes and adherence in Syria's first smoking cessation trial.
AB  - OBJECTIVE: To determine the feasibility of implementing cessation interventions
      in Syria. METHODS: We randomized 50 smokers to either a brief or intensive
      behavioral cessation intervention. Adherence to treatment and cessation through 3
      months postcessation were calculated. RESULTS: Adherence in the intensive group
      was only moderate and was associated with smoking for more years and higher self
      efficacy. Cessation rates in the brief and intensive intervention groups were 16%
      and 4%, respectively. Nicotine dependence predicted abstinence at 3 months.
      CONCLUSION: Important barriers to cessation included perceived dependence, lack
      of access to pharmacotherapy, poor social support, and water pipe smoking.

PMID- 18052856
TI  - Assessing self-management and spirituality practices among older women.
AB  - OBJECTIVE: To understand the role of spirituality in the self-management of
      cardiovascular disease and arthritis. METHOD: Self-management practices were
      selected from older women enrolled in a longitudinal study (N=492) whereas 24 of
      the enrolled participants were selected for an in-depth interview regarding the
      role of spirituality in their self-management practices. RESULTS: Significant
      differences were found in the level of spirituality in self-management behaviors
      based on ethnicity. The qualitative analyses reaffirmed the importance of
      spirituality in the self-management of chronic illness. CONCLUSION: Using
      multiple methodologies, this study elucidated the role of spirituality in the
      self-management of chronic illness among older women.

PMID- 18052857
TI  - ViewPoint: conversation with Lloyd J. Kolbe, PhD.

PMID- 18052858
TI  - Knowledge, attitudes, and behaviors of Chinese hepatitis B screening and
      vaccination.
AB  - OBJECTIVE: To measure the knowledge, attitudes, and behaviors of Hepatitis B
      (HBV) screening and vaccination in the Chinese American population. METHODS: A
      cross-sectional study was conducted among 429 Chinese in New York City.
      Participants were recruited from Chinese community-based organizations.
      Descriptive statistics and chi-square tests of independence were conducted.
      RESULTS: Knowledge level of HBV risk factors and screening and vaccination rates
      are low. There were significant differences in screening and vaccination by
      marital and health insurance status, language, gender, education, and income.
      CONCLUSIONS: Findings suggested that interventions for Chinese Americans and
      health care providers can substantially increase screening and vaccination rates.

PMID- 18052859
TI  - Influence of coping with prostate cancer threat on frequency of digital rectal
      examinations.
AB  - OBJECTIVES: To determine the role of personality variables in coping with cancer
      threat in the receipt of digital rectal examinations among men from 7 ethnic
      subpopulations composing 3 major ethnic groups. METHODS: Three hundred eight men
      were assessed on how often they obtained digital rectal exams and their
      likelihood of coping with a hypothetical cancer diagnosis. RESULTS: There were
      ethnic disparities in screening frequency that were not accounted for by
      demographic/background variables. Coping styles that reflect problem solving, use
      of social support, and avoidance provided unique and additional variance in
      understanding these disparities. CONCLUSIONS: Cancer researchers and educators
      must account for heterogeneity within typical major ethnic groups, as well as
      consider the role of personality variables, as they differentially predict
      outcomes in ethnic subpopulations.

PMID- 18052860
TI  - Workplace sun protection policies and employees' sun-related skin damage.
AB  - OBJECTIVES: To investigate whether mandatory sun protection for outdoor workers
      in tropical regions is associated with reduced sun damage. METHODS: Survey of 26
      employees working under mandatory sun protection policy was compared to survey of
      21 employees working under voluntary sun protection policy. RESULTS: Voluntary
      sun protection associated with employees having more solar keratoses on dorsum of
      right hand (P=0.006) and more previously excised self-reported skin cancers
      (P=0.008). CONCLUSIONS: Employees working under mandatory sun protection policy
      had reduced sun damage, a likely consequence of less sun exposure.

PMID- 18052861
TI  - A structural model of alcohol use pathways among Latino youth.
AB  - OBJECTIVES: To determine the pathways to alcohol use among adolescents. METHODS:
      A cross-sectional study of risk and protective factors among a sample of Latino
      youth (aged 11-13) was conducted. RESULTS: Peer norms and school connectedness
      had direct pathways to alcohol use. Self-concept was related to peer norms. Youth
      who were less acculturated were more likely to believe that their peers drank.
      Family monitoring, connectedness, and academic support did not have direct
      pathways to alcohol use. CONCLUSIONS: Peer norms appear critical in shaping
      adolescent involvement with alcohol. The protective influence of family and
      academic support appear to be indirect.

PMID- 18052862
TI  - From HIV AIDS, TB to H. pylori and other infections in Africa.

PMID- 18052863
TI  - Eligibility for HIV/AIDS treatment among adults in a medical emergency setting at
      an urban hospital in Uganda.
AB  - BACKGROUND: Despite global effort to scale up access to antiretroviral therapy
      (ART), many people in need of HIV/AIDS care in Uganda have not been reached. HIV
      testing and ART are not widely offered as routine medical services and data on
      HIV/AIDS in emergency settings in Sub-Saharan Africa is limited. We determined
      the HIV prevalence and eligibility for ART in a medical emergency unit at Mulago
      hospital. METHODS: In a cross-sectional study, we interviewed 223 patients who
      were systematically selected from the patients' register from October through
      December 2004. HIV testing was offered routinely and results were delivered
      within 30 minutes. We evaluated HIV infected patients for WHO clinical stage of
      disease and referred them for HIV/AIDS care. RESULTS: Out of 223 patients, 111
      (50%) had HIV infection of whom 78 (70%) had WHO clinical stage 3 and 4 of
      disease thereby requiring ART. Overall, 84 out of 111 (76%) HIV positive patients
      had not received any specific HIV/AIDS care. CONCLUSION: The burden of HIV
      infection in the medical emergency unit is high and majority of the patients who
      required ART had no prior HIV/AIDS care. We recommend scale up of HIV/AIDS care
      in acute care settings in order to increase access to ART.

PMID- 18052864
TI  - Human T-cell lymphotropic virus in a population of pregnant women and commercial
      sex workers in South Western Nigeria.
AB  - BACKGROUND: Over 20 million persons are infected with HTLV-I/II globally. The
      virus is endemic in Africa and it is also transmitted sexually. Continued
      identification of high risk groups is important for the control of the disease.
      OBJECTIVES: To determine the prevalence of HTLV infection amongst two highly
      sexually active groups, pregnant women and CSWs in South Western Nigeria.
      METHODS: Serum samples were tested for the presence of HTLV-I/II antibodies using
      the Vironostika HTLV-I/II micro ELISA system. RESULTS: A total of 364 serum
      samples collected from pregnant women, commercial sex worker (CSW) and secondary
      school students (control group) from Ibadan. While only 4 (5.1%) of 78 secondary
      school students (average age: 13 years) were reactive for HTLV infection, 20
      (16.7%) of 120 pregnant women (average age: 26 years) and 38 (22.9%) of 166 CSWs
      (average age: 23 years) were found to have antibodies against HTLV in their sera.
      The results of this study thus show that HTLV infection is active in the
      population although higher in pregnant women (although not statistically
      significant) and CSWs (p>0.05). Pregnant women and CSWs are therefore at a higher
      risk of HTLV transmission than other members of the population. CONCLUSION:
      Routine screening for HTLV infection may go a long way to understanding the
      epidemiology of HTLV infection in Nigeria and subsequently provide tools for its
      prevention and control.

PMID- 18052865
TI  - Anti-retroviral therapy induced diabetes in a Nigerian.
AB  - BACKGROUND: Anti-retroviral therapy (ART) using Highly Active Anti-retroviral
      Therapy (HAART) has led to considerable reduction in morbidity and mortality
      associated with human Immune deficiency virus (HIV) infection. This has led to
      increased life expectancy in HIV infected individuals on one hand, and side
      effects of chronic administration of these drugs on the other. One of such
      untoward effects is the association of anti-retroviral drugs especially the
      protease inhibitors (PI's) with metabolic derangements such as dyslipidaemia,
      lipodystrophy, insulin resistance and rarely Diabetes mellitus. Although there is
      extensive literature on this dysmetabolic syndrome in the Western World; there is
      to our knowledge no previous report from Nigeria. OBJECTIVE: to report a case of
      diabetes mellitus following the initiation of anti-retroviral therapy. METHODS: a
      case report of diabetes mellitus induced by anti-retroviral therapy in a 48 year
      old Nigerian male. CONCLUSION: Awareness and high index of suspicion is required
      to identify the metabolic complications of ART.

PMID- 18052866
TI  - The challenge of re-treatment pulmonary tuberculosis at two teaching and referral
      hospitals in Uganda.
AB  - BACKGROUND: With an annual tuberculosis (TB) incidence of about 350 cases per
      100,000 of the population, Uganda is a high burden country. Moreover, it is
      evident that some TB patients have been treated for a previous episode of the
      disease. OBJECTIVE: To highlight the burden of re-treatment pulmonary TB and
      examine patient factors associated with re-treatment among adults at two teaching
      and referral hospitals, Mbarara and Mulago. METHODS: A descriptive cross
      sectional study with data collection between September 2004 and March 2005; we
      calculated the prevalence and used logistic regression to explore factors
      associated with re-treatment. RESULTS: The prevalence of re-treatment pulmonary
      TB at Mbarara based on medical records was 30.0% (95%CI: 21.2 to 40.0), and 21.3%
      (95%CI: 12.9 to 31.8) from exit interviews. The corresponding estimates at Mulago
      hospital were 12.0% (95% CI: 6.4 to 20.0) and 43.9% (33.0 to 55.3). Compared to
      the 18-26 year age category, the prevalence odds ratio (POR) for a seven-year
      increase in age was 1.54 (95%CI: 1.04-2.28; p = 0.027), while female patients
      were 0.39 (95%CI: 0.17-0.90; p = 0.025) times less likely to report re-treatment
      disease than males, in this facility-based study. CONCLUSIONS: Re-treatment
      pulmonary TB is frequent at the two teaching and referral hospitals. A
      contribution to re-treatment prevention should entail more rigorous management of
      new TB cases, particularly at lower levels of care.

PMID- 18052867
TI  - Antibiotic resistance of Helicobacter pylori from patients in Ile-Ife, South
      west, Nigeria.
AB  - BACKGROUND: Helicobacter pylori has become recognized as a major cause of
      gastroduodenal diseases in man. Evidence indicates that once acquired, H. pylori
      persists, usually for life unless eradicated by antimicrobial therapy. Over the
      past few years, we have accumulated some knowledge of the epidemiology of H.
      pylori in Ile-Ife, South-West Nigeria. In one collaborative study, we detected H.
      pylori in 195 (73%) patients referred for endoscopy at Obafemi Awolowo University
      Teaching Hospitals Complex (OAUTHC). Furthermore we have observed a variegated
      gastric inflammatory response and atrophy including atrophic pangastritis but are
      yet to demonstrate MALToma in any of our patients. In addition we have
      demonstrated that dental plaque is a possible source of gastric H. pylori
      infection and such an endogenous source could account for difficulty in
      eradication leading to re-infection. Presently, infected patients are treated
      with standard combination therapy made up of amoxycilin and ciprofloxacin with a
      proton pump inhibitor/bismuth. Reports however have shown that the incidence of
      antimicrobial resistance in Helicobacter pylori is a growing problem and which
      has been linked with failures in treatment and eradication. Given this situation
      it has become necessary to have information about the susceptibility of isolates
      to particular antimicrobial agents before the selection of an appropriate
      treatment regimen. OBJECTIVES: More recently, we sought to study antimicrobial
      susceptibility of locally isolated H. pylori strains. METHODS: We subjected 32
      isolates to antimicrobial susceptibility testing against seven agents. RESULTS:
      All the isolates showed multiple acquired antimicrobial resistance as they were
      all resistant to amoxicillin, clarithromycin, metronidazole, while 29/31, 27/31
      showed resistance to rifampicin and tetracycline respectively. Five (15.6%) of
      these isolates showed resistance to ciprofloxacin. CONCLUSIONS: Our findings
      suggest that H. pylori strains isolated within our study environment have
      acquired resistance to all the commonly prescribed antibiotics. On the basis of
      the findings it would be necessary to re-evaluate the eradication treatment
      regime in our setting.

PMID- 18052868
TI  - Drug sensitivity patterns of bacterial isolates from septic post-operative wounds
      in a regional referral hospital in Uganda.
AB  - BACKGROUND: Wound infections have been a problem in the field of surgery for a
      long time. Advances in control of infections have not completely eradicated this
      problem because of development of drug resistance. Antimicrobial resistance can
      increase complications and costs associated with procedures and treatment.
      OBJECTIVE: A study was carried out on drug sensitivity patterns of bacterial
      isolates from septic postoperative wounds in Jinja hospital, Uganda. This study
      was designed to determine the distribution of bacterial pathogens isolated from
      septic post-operative wounds and their antimicrobial susceptibility patterns.
      METHOD: Specimens of pus swabs were collected aseptically and analysed in the
      laboratory. Colony characteristics and Grams technique were used to differentiate
      the organisms. Biochemical tests were done to confirm the species of the
      organisms. Sensitivity testing was done on the isolates using the disk diffusion
      method. RESULTS: Pathogenic bacteria were recovered from 58.5% of the specimens.
      The isolates were: S.aureus (45.1%), Coliforms (16.9%), Proteus mirabilis
      (11.3%), P.aeruginosa (9.9%), Klebsiella pneumoniae (7.0%) and Enterobacter spp
      (2.82%). Most of the organisms were sensitive to gentamicin, ciprofloxacin and
      ceftazidime. There was resistance to ampicillin, amoxycillin and chloramphenicol.
      Staphylococcus aureus was generally sensitive to gentamicin (87.5%),
      ciprofloxacin (68.7%) and methicillin (75%), but resistant to erythromycin
      (56.2%) and ampicillin (97%). Most of the gram-negative bacteria isolated
      (Coliforms, P.aeruginosa, E.coli, Proteus mirabilis, and Klebsiella pneumoniae)
      were sensitive to Ciprofloxacin, Gentamicin and Ceftazidime but resistant to
      Ampicillin, Amoxycillin and Chloramphenicol. Methicillin-resistant Staphylococcus
      aureus (MRSA) strains formed 25% of this species. Pseudomonas aeruginosa was
      sensitive to gentamicin (87.5%) and ceftazidime (85.7%) but showed resistance to
      ciprofloxacin (57.2%). Some organisms e.g. S.aureus, Pseudomonas aeruginosa and
      Proteus mirabilis exhibited multi-drug resistance to the antibiotics tested.
      CONCLUSION: Since a high proportion of samples had positive cultures, infection
      control is recommended as a strategy to minimise spread of resistant organisms.
      It is recommended that gentamicin, ciprofloxacin and ceftazidime be used in
      preference to ampicillin and amoxycillin for treatment of septic wounds. There is
      need to develop national surveillance of antibiotic- resistant organisms.

PMID- 18052869
TI  - Antibacterial activity of Thonningia sanguinea against some multi-drug resistant
      strains of Salmonella enterica.
AB  - BACKGROUND: The emergence of strains of S.enterica with multiple drug resistance
      (MDR) is of great concern worldwide.The extracts of flowers of Thonningia
      sanguinea are used in traditional medicine in Ivory Coast to treat diarrhoeal
      diseases including salmonellosis. Previous studies had shown inhibition of the
      MDR strain Salmonella Enteritidis lysotype 6. OBJECTIVES: The present study
      focused to investigate the effect of the extract of the flowers of Thonningia
      sanguinea on some clinical MDR strains of Salmonella namely S. Tyhpi, S.
      Typhimurium, S. Hadar and a sensitive strain (S. Enteritidis). METHODS: The
      antimicrobial parameters were determined by double dilution with agar slant
      method. This method led us to determine MIC, IC50 and MBC. RESULTS: The MDR
      strain of S.Typhimurium presented the highest MIC (2.5 mg/ml) whereas the other
      two MDR strains (S. Hadar, S. Typhi) and the sensitive one (S. Enteritidis) had
      the same MIC (1.25 mg/ml). The four strains presented the same MBC (2.5 mg/ml).
      The MDR strain of S. Typhi is the most susceptible strain to the aqueous extract
      of the flowers of Thonningia sanguinea according to The IC50 values. CONCLUSIONS:
      The aqueous extract of Thonningia sanguinea can provide an alternative therapy
      for the treatment of salmonellosis, mainly for typhoid fever caused by MDR
      strains of S Typhi. The extract also inhibits S.Hadar a MDR emerging strain in
      Ivory Coast.

PMID- 18052870
TI  - Honey: a reservoir for microorganisms and an inhibitory agent for microbes.
AB  - BACKGROUND: Honey is an ancient remedy for the treatment of infected wounds,
      which has recently been 'rediscovered' by the medical profession. The use to
      which honey is put in medical care is increasing daily with many authors pointing
      out its importance and role in wound care. There have been reports that honey
      contains many microorganisms including bacteria and fungi. OBJECTIVE: The aim of
      this paper is to highlight the various uses, organisms commonly found in honey,
      how the organisms arrived in the honey and their effects on wounds and wound
      care. Would the presence of these organisms not constitute a limiting factor to
      the use of honey in wound management? This is what this review aims to answer.
      METHODS: A literature search was done on honey using pubmed, google, local books
      and journals. Relevant journals were extracted and discussed with emphasis on the
      antimicrobial properties as well as microbial content of honey and the
      implications of these. RESULTS: The production of honey as well as the storing
      process account for the presence of microorganisims. Most of these organisms are
      said to be in inactive forms as they can hardly survive in honey because of its
      several properties including hygroscopicity, hyperosmolarity, acidity, peroxide
      content, antibiotic activities etc. However there is a need for caution in the
      use of honey in wound management. CONCLUSION: We suggest that wounds to be
      treated with honey should be investigated i.e with a swab for the microorganisms
      present on the wound and their sensitivity to the honey before commencing honey
      treatment. This will help in carefully selecting wounds that might do well with
      honey treatment not withstanding other properties of honey that aid wound
      healing.

PMID- 18052871
TI  - Burkitt's lymphoma in Africa, a review of the epidemiology and etiology.
AB  - Burkitt's lymphoma (BL) was first described in Eastern Africa, initially thought
      to be a sarcoma of the jaw. Shortly it became well known that this was a distinct
      form of Non Hodgkin's lymphoma. The disease has given insight in all aspects of
      cancer research and care. Its peculiar epidemiology has led to the discovery of
      Epstein Barr virus (EBV) and its importance in the cause of several viral
      illnesses and malignancies. The highest incidence and mortality rates of BL are
      seen in Eastern Africa. BL affects mainly children, and boys are more susceptible
      than girls. Evidence for a causal relationship between EBV and BL in the endemic
      form is fairly strong. Frequency of association between EBV and BL varies between
      different patient groups and different parts of the world. EBV may play a role in
      the pathogenesis of BL by deregulation of the oncogene c-MYC by chromosomal
      translocation. Although several studies suggest an association between malaria
      and BL, there has never been a conclusive population study in support of a direct
      role of malaria in causation of BL. The emergence of HIV and a distinct subtype
      of BL in HIV infected have brought a new dimension to the disease particularly in
      areas where both HIV and BL are endemic. BL has been reported as a common
      neoplasmin HIV infected patients, but not in other forms of immuno-depression,
      and the occurrence of BL seems to be higher amongst HIV positive adults, while
      the evidence of an association amongst children is still disputed. The role of
      other possible risk factors such as low socio-economical status, exposure to a
      plant species common in Africa called Euphorbiaceae, exposure to pesticies and to
      other infections such as schistosomiasis and arbovirus (an RNA virus transmitted
      by insect vectors) remain to be elucidated.

PMID- 18052872
TI  - A community-based investigation of the avoidable factors of maternal mortality in
      Nigeria: the pilot experience.
AB  - BACKGROUND: Reduction of maternal mortality is one of the major goals of several
      recent international conferences and has been included within the Millennium
      Development Goals. However, because measuring maternal mortality is difficult and
      complex, reliable estimates of the dimensions of the problem are not generally
      available and assessing progress towards the goal is difficult in some countries.
      Reliable baseline data are crucial to effectively track progress and measure that
      targets or goals of reducing maternal mortality have been met. OBJECTIVES: The
      objectives of this pilot study were: to test adequacy of research instruments; to
      improve research techniques; to determine an appropriate workload; to determine
      the time required for interviews; and to assess the feasibility of a (full-scale)
      study/survey. METHODS: This pilot study was conducted between 11(th) April and
      22(nd) April 2005. 420 houses were visited and interviews of 420 respondents
      between the ages of 15-49 were conducted in a randomly pre-selected Local
      Government Area of Oyo state using a structured instrument developed using the
      principles of the Sisterhood Method. RESULTS: There was willingness of the public
      to participate in the study. The response rate was 100%. There was no issue
      raised as regards the structure, wording and translation of the questionnaire.
      This pilot study uncovered local political problems and other issues that may be
      encountered during the main study. CONCLUSIONS: The pilot raised a number of
      fundamental issues related to the process of designing the research instrument,
      identifying and recruiting Data Collectors, training and supervision of Data
      Collectors and the research project, gaining access to respondents and obtaining
      support and approval from "gatekeepers". This paper highlights the lessons
      learned and reports practical issues that occurred during pilot study.

PMID- 18052873
TI  - Presence of lupus anticoagulant in an asymptomatic Nigerian.
AB  - BACKGROUND: The lupus anticoagulant (LA) is one of the antiphospholipid
      antibodies (aPL), which prolong phospholipid- dependent coagulation tests by
      interfering with coagulation reactions that depend on protein - phospholipid
      complexes in vitro. METHOD: A 25 year old 'healthy' male Nigerian was screened
      for the presence of any coagulation abnormality using the KCT, PT and platelet
      count; after volunteering for his plasma to be used in the preparation of normal
      pooled plasma in a study. RESULTS: He was discovered to have a prolonged KCT, PT
      and normal platelet count. Based on the prolonged KCT his plasma was subjected to
      mixing studies with various concentration of normal pooled plasma; the KCT index
      was calculated and a curve was plotted. His KCT index was 1.6 and the curve
      convex in the left axis suggesting the presence of LA. His past medical history
      and physical examination were not remarkable. Three months after the initial
      study, a repeat KCT index was 1.4 and the subject asymptomatic. CONCLUSION: From
      literature review this is the first report of LA in an asymptomatic adult
      Nigerian; the importance of this finding is discussed.

PMID- 18052874
TI  - Chloroquine has not disappeared.
AB  - Chloroquine (CHQ), an antimalarial, is also used as an anti-inflammatory drug for
      systemic lupus erythematosus and rheumatoid arthritis (RA). Hydroxychloroquine
      (HCQ) reduces the frequency of organ involvement and disease flares, and relieves
      skin and joint symptoms. CHQ reduces the immunologically-mediated inflammation of
      the joints. HCQ and combination therapies have a significant benefit on
      synovitis, pain and physical disability on RA. We advocate the investment of
      resistance Plasmodium prevalence determinations in countries beset by malaria,
      and to match thereafter the quantity of persons administered CHQ. Follow-up
      investigations are essential to diagnose and prevent visual damage.

PMID- 18052875
TI  - Monochrome versus color softcopy displays for teleradiology: observer performance
      and visual search efficiency.
AB  - This study evaluated the potential clinical utility for teleradiology of a high
      performance (3-mega-pixel) color softcopy display compared with two monochrome
      softcopy displays: one of comparable luminance (250 cd/m2) and one of higher
      luminance (450 cd/m2). Six radiologists viewed 50 chest images, half with nodules
      and half without, once on each display. Eye position was recorded on a subset of
      the images to characterize visual search efficiency. There was no statistically
      significant difference in diagnostic performance as a function of monitor
      (F=1.176, p=0.3127), although the higher luminance display yielded slightly
      better performance. In terms of total viewing time, there were no statistically
      significant differences between the three monitors (F=1.478, p=0.2298). The dwell
      times associated with true- and false-positive decisions were shortest for the
      high luminance monochrome display, longer for the low luminance monochrome, and
      longest for the low luminance color display. Dwells for the false-negative
      decisions were longest for the high luminance monochrome display, shorter for the
      low luminance monochrome, and shortest for the low luminance color display. The
      true negative dwells were not significantly different. The study suggests that
      high-performance color displays can be used for teleradiologic interpretation of
      diagnostic images without negatively impacting diagnostic accuracy or visual
      search efficiency to a significant degree.

PMID- 18052876
TI  - Comment on: The case for prioritizing research on late-onset life-extension
      interventions in mammals.

PMID- 18052878
TI  - Characterization of natural and induced variation in the LOV1 gene, a CC-NB-LRR
      gene conferring victorin sensitivity and disease susceptibility in Arabidopsis.
AB  - The fungus Cochliobolus victoriae, the causal agent of Victoria blight, produces
      a compound called victorin that is required for pathogenicity of the fungus.
      Victorin alone reproduces disease symptoms on sensitive plants. Victorin
      sensitivity and susceptibility to C. victoriae were originally described on oats
      but have since been identified on Arabidopsis thaliana. Victorin sensitivity and
      disease susceptibility in Arabidopsis are conferred by LOV1, a coiled-coil
      nucleotide-binding-leucine-rich repeat (CC-NB-LRR) protein. We sequenced the LOV1
      gene from 59 victorin-insensitive mutants and found that the spectrum of
      mutations causing LOV1 loss of function was similar to that found to cause loss
      of function of RPM1, a CC-NB-LRR resistance protein. Also, many of the mutated
      residues in LOV1 are in conserved motifs required for resistance protein
      function. These data indicate that LOV1 may have a mechanism of action similar to
      resistance proteins. Victorin sensitivity was found to be the prevalent phenotype
      in a survey of 30 Arabidopsis ecotypes, and we found very little genetic
      variation among LOV1 alleles. As selection would not be expected to preserve a
      functional LOV1 gene to confer victorin sensitivity and disease susceptibility,
      we propose that LOV1 may function as a resistance gene to a naturally-occurring
      pathogen of Arabidopsis.

PMID- 18052879
TI  - Identification of Plum pox virus pathogenicity determinants in herbaceous and
      woody hosts.
AB  - Plum pox virus (PPV) is a member of the genus Potyvirus that is able to infect a
      large variety of plant species, including trees of the genus Prunus, its natural
      host. When some PPV isolates are propagated for an extended time in herbaceous
      plants, their ability to infect trees is reduced. The molecular basis of this
      change in host infectivity is poorly understood. We report the construction of
      hybrid viruses from cDNA clones of two D-strain isolates of PPV, PPV-D and PPV-R,
      which differ in their host range. PPV-D can infect GF305 peach seedlings
      efficiently, however, it is unable to infect Nicotiana clevelandii plants.
      Conversely, PPV-R infects N. clevelandii, but not GF305 peach seedlings. The
      analyses of the hybrid viruses showed that, although determinants of PPV
      pathogenicity are extensively spread throughout the PPV genome, the 3' terminal
      region of the PPV-R genome, including the 3' noncoding region and the coding
      regions for the coat protein (CP), NIb, and part of NIa protein, is sufficient to
      confer infectivity of N. clevelandii in a PPV-D background. Our data demonstrate
      a high concentration of amino acid substitutions in the CP and a host-specific
      effect of a deletion at the N terminus of this protein in PPV pathogenicity in
      peach and N. clevelandii infectivity experiments. These results suggest that
      relevant host specificity determinants are located in the N-terminal region of
      the CP. The analyses of the PPV-R and PPV-D chimeras also showed that key host
      specific pathogenicity determinants lie in the 5' terminal third of the PPV
      genome, a region that spans proteins P1, HCPro, and P3. The selection of
      mutations in only a few specific residues in proteins P1, P3, and 6K1 after
      partial adaptation of a chimeric virus (BD-GFP) to N. clevelandii further
      suggests a relevant role for these proteins in host adaptation.

PMID- 18052880
TI  - Naturally occurring broad-spectrum powdery mildew resistance in a Central
      American tomato accession is caused by loss of mlo function.
AB  - The resistant cherry tomato (Solanum lycopersicum var. cerasiforme) line LC-95,
      derived from an accession collected in Ecuador, harbors a natural allele (ol-2)
      that confers broad-spectrum and recessively inherited resistance to powdery
      mildew (Oidium neolycopersici). As both the genetic and phytopathological
      characteristics of ol-2-mediated resistance are reminiscent of powdery mildew
      immunity conferred by loss-of-function mlo alleles in barley and Arabidopsis, we
      initiated a candidate-gene approach to clone Ol-2. A tomato Mlo gene (SlMlo1)
      with high sequence-relatedness to barley Mlo and Arabidopsis AtMLO2 mapped to the
      chromosomal region harboring the Ol-2 locus. Complementation experiments using
      transgenic tomato lines as well as virus-induced gene silencing assays suggested
      that loss of SlMlo1 function is responsible for powdery mildew resistance
      conferred by ol-2. In progeny of a cross between a resistant line bearing ol-2
      and the susceptible tomato cultivar Moneymaker, a 19-bp deletion disrupting the
      SlMlo1 coding region cosegregated with resistance. This polymorphism results in a
      frameshift and, thus, a truncated nonfunctional SlMlo1 protein. Our findings
      reveal the second example of a natural mlo mutant that possibly arose post
      domestication, suggesting that natural mlo alleles might be evolutionarily short
      lived due to fitness costs related to loss of mlo function.

PMID- 18052881
TI  - The Arabidopsis gain-of-function mutant ssi4 requires RAR1 and SGT1b
      differentially for defense activation and morphological alterations.
AB  - A gain-of-function mutation in resistance (R) gene SSI4 causes constitutive
      activation of defense responses, spontaneous necrotic lesion formation, enhanced
      resistance against virulent pathogens, and a severe dwarf phenotype. Genetic
      analysis revealed that ssi4-induced H(2)O(2) accumulation and spontaneous cell
      death require RAR1, whereas ssi4-mediated stunting is dependent on SGT1b. By
      contrast, both RAR1 and SGT1b are required in a genetically additive manner for
      ssi4-induced disease resistance, SA accumulation, and lesion formation after
      pathogen infection. These data point to cooperative yet distinct functions of
      RAR1 and SGT1b in responses conditioned by a deregulated nucleotide-binding
      leucine-rich repeat protein. We also found that RAR1 and SGT1b together
      contribute to basal resistance because an ssi4 rar1 sgt1b triple mutant exhibited
      enhanced susceptibility to virulent pathogen infection compared with wild-type
      SSI4 plants. All ssi4-induced phenotypes were suppressed when plants were grown
      at 22 degrees C under high relative humidity. However, low temperature (16
      degrees C) triggered ssi4-mediated cell death via an RAR1-dependent pathway even
      in the presence of high humidity. Thus, multiple environmental factors impact on
      ssi4 signaling, as has been observed for other constitutive defense mutants and R
      gene-triggered pathways.

PMID- 18052882
TI  - Defects in rhizobial cyclic glucan and lipopolysaccharide synthesis alter legume
      gene expression during nodule development.
AB  - cDNA array technology was used to compare transcriptome profiles of Lotus
      japonicus roots inoculated with a Mesorhizobium loti wild-type and two mutant
      strains affected in cyclic beta(1-2) glucan synthesis (cgs) and in
      lipopolysaccharide synthesis (lpsbeta2). Expression of genes associated with the
      development of a fully functional nodule was significantly affected in plants
      inoculated with the cgs mutant. Array results also revealed that induction of
      marker genes for nodule development was delayed when plants were inoculated with
      the lpsbeta2 mutant. Quantitative real-time reverse-transcriptase polymerase
      chain reaction was used to quantify gene expression of a subset of genes involved
      in plant defense response, redox metabolism, or genes that encode for nodulins.
      The majority of the genes analyzed in this study were more highly expressed in
      roots inoculated with the wild type compared with those inoculated with the cgs
      mutant strain. Some of the genes exhibited a transient increase in transcript
      levels during intermediate steps of normal nodule development while others
      displayed induced expression during the final steps of nodule development.
      Ineffective nodules induced by the glucan mutant showed higher expression of
      phenylalanine ammonia lyase than wild-type nodules. Differences in expression
      pattern of genes involved in early recognition and signaling were observed in
      plants inoculated with the M. loti mutant strain affected in the synthesis of
      cyclic glucan.

PMID- 18052883
TI  - Genetic dissection of resistance to anthracnose and powdery mildew in Medicago
      truncatula.
AB  - Medicago truncatula was used to characterize resistance to anthracnose and
      powdery mildew caused by Colletotrichum trifolii and Erysiphe pisi, respectively.
      Two isolates of E. pisi (Ep-p from pea and Ep-a from alfalfa) and two races of C.
      trifolii (races 1 and 2) were used in this study. The A17 genotype was resistant
      and displayed a hypersensitive response after inoculation with either pathogen,
      while lines F83005.5 and DZA315.16 were susceptible to anthracnose and powdery
      mildew, respectively. To identify the genetic determinants underlying resistance
      in A17, two F7 recombinant inbred line (RIL) populations, LR4 (A17 x DZA315.16)
      and LR5 (A17 x F83005.5), were phenotyped with E. pisi isolates and C. trifolii
      races, respectively. Genetic analyses showed that i) resistance to anthracnose is
      governed mainly by a single major locus to both races, named Ct1 and located on
      the upper part of chromosome 4; and ii) resistance to powdery mildew involves
      three distinct loci, Epp1 on chromosome 4 and Epa1 and Epa2 on chromosome 5. The
      use of a consensus genetic map for the two RIL populations revealed that Ct1 and
      Epp1, although located in the same genome region, were clearly distinct. In
      silico analysis in this region identified the presence of several clusters of
      nucleotide binding site leucine-rich repeat genes. Many of these genes have
      atypical resistance gene analog structures and display differential expression
      patterns in distinct stress-related cDNA libraries.

PMID- 18052884
TI  - Hessian fly (Mayetiola destructor) attack causes a dramatic shift in carbon and
      nitrogen metabolism in wheat.
AB  - Carbon and nitrogen (C/N) metabolism and allocation within the plant have
      important implications for plant-parasite interactions. Many plant parasites
      manipulate the host by inducing C/N changes that benefit their own survival and
      growth. Plant resistance can prevent this parasite manipulation. We used the
      wheat-Hessian fly (Mayetiola destructor) system to analyze C/N changes in plants
      during compatible and incompatible interactions. The Hessian fly is an insect but
      shares many features with plant pathogens, being sessile during feeding stages
      and having avirulence (Avr) genes that match plant resistance genes in gene-for
      gene relationships. Many wheat genes involved in C/N metabolism were
      differentially regulated in plants during compatible and incompatible
      interactions. In plants during compatible interactions, the content of free
      carbon-containing compounds decreased 36%, whereas the content of free nitrogen
      containing compounds increased 46%. This C/N shift was likely achieved through a
      coordinated regulation of genes in a number of central metabolic pathways,
      including glycolysis, the tricarboxylic acid cycle, and amino-acid synthesis. Our
      data on plants during compatible interactions support recent findings that
      Hessian fly larvae create nutritive cells at feeding (attack) sites and
      manipulate host plants to enhance their own survival and growth. In plants during
      incompatible interactions, most of the metabolic genes examined were not affected
      or down-regulated.

PMID- 18052885
TI  - Distinct mechanisms govern the dosage-dependent and developmentally regulated
      resistance conferred by the maize Hm2 gene.
AB  - The maize Hm2 gene provides protection against the leaf spot and ear mold disease
      caused by Cochliobolus carbonum race 1 (CCR1). In this regard, it is similar to
      Hm1, the better-known disease resistance gene of the maize-CCR1 pathosystem.
      However, in contrast to Hm1, which provides completely dominant resistance at all
      stages of plant development, Hm2-conferred resistance is only partially dominant
      and becomes fully effective only at maturity. To investigate why Hm2 behaves in
      this manner, we cloned it on the basis of its homology to Hm1. As expected, Hm2
      is a duplicate of Hm1, although the protein it encodes is grossly truncated
      compared with HM1. The efficacy of Hm2 in conferring resistance improves
      gradually over time, changing from having little or no impact in seedling tissues
      to providing complete immunity at anthesis. The developmentally specified
      phenotype of Hm2 is not dictated transcriptionally, because the expression level
      of the gene, whether occurring constitutively or undergoing substantial and
      transient induction in response to infection, does not change with plant age. In
      contrast, however, the Hm2 transcript is much more abundant in plants homozygous
      for this gene compared with plants that contain only one copy of the gene,
      suggesting a transcriptional basis for the dosage-dependent nature of Hm2. Thus,
      different mechanisms seem to underlie the developmentally programmed versus the
      partially dominant resistance phenotype of Hm2.

PMID- 18052886
TI  - Transformation-mediated complementation of a FUM gene cluster deletion in
      Fusarium verticillioides restores both fumonisin production and pathogenicity on
      maize seedlings.
AB  - The filamentous ascomycete Fusarium verticillioides is a pathogen of maize and
      produces the fumonisin mycotoxins. However, a distinct population of F.
      verticillioides is pathogenic on banana and does not produce fumonisins.
      Fumonisin-producing strains from maize cause leaf lesions, developmental
      abnormalities, stunting, and sometimes death of maize seedlings, whereas
      fumonisin-nonproducing banana strains do not. A Southern analysis of banana
      strains did not detect genes in the fumonisin biosynthetic gene (FUM) cluster but
      did detect genes flanking the cluster. Nucleotide sequence analysis of the
      genomic region carrying the flanking genes revealed that the FUM cluster was
      absent in banana strains except for portions of FUM21 and FUM19, which are the
      terminal genes at each end of the cluster. Polymerase chain reaction analysis
      confirmed the absence of the cluster in all banana strains examined.
      Cotransformation of a banana strain with two overlapping cosmids, which together
      contain the entire FUM cluster, yielded fumonisin-producing transformants that
      were pathogenic on maize seedlings. Conversely, maize strains that possess the
      FUM cluster but do not produce fumonisins because of mutations in FUM1, a
      polyketide synthase gene, were not pathogenic on maize seedlings. Together, the
      data indicate that fumonisin production may have been lost by deletion of the FUM
      cluster in the banana population of F. verticillioides but that fumonisin
      production could be restored by molecular genetic complementation. The results
      also indicate that fumonisin production by F. verticillioides is required for
      development of foliar disease symptoms on maize seedlings.

PMID- 18052887
TI  - Maize 9-lipoxygenase ZmLOX3 controls development, root-specific expression of
      defense genes, and resistance to root-knot nematodes.
AB  - Root-knot nematodes (RKN) are severe pests of maize. Although lipoxygenase (LOX)
      pathways and their oxylipin products have been implicated in plant-nematode
      interactions, prior to this report there was no conclusive genetic evidence for
      the function of any plant LOX gene in such interactions. We showed that
      expression of a maize 9-LOX gene, ZmLOX3, increased steadily and peaked at 7 days
      after inoculation with Meloidogyne incognita RKN. Mu-insertional lox3-4 mutants
      displayed increased attractiveness to RKN and an increased number of juveniles
      and eggs. A set of jasmonic acid (JA)- and ethylene (ET)-responsive and
      biosynthetic genes as well as salicylic acid (SA)-dependent genes were
      overexpressed specifically in the roots of lox3-4 mutants. Consistent with this,
      levels of JA, SA, and ET were elevated in lox3-4 mutant roots, but not in leaves.
      Unlike wild types, in lox3-4 mutant roots, a phenylalanine ammonia lyase (PAL)
      gene was not RKN-inducible, suggesting a role for PAL-mediated metabolism in
      nematode resistance. In addition to these alterations in the defense status of
      roots, lox3-4 knockout mutants displayed precocious senescence and reduced root
      length and plant height compared with the wild type, suggesting that ZmLOX3 is
      required for normal plant development. Taken together, our data indicate that the
      ZmLOX3-mediated pathway may act as a root-specific suppressor of all three major
      defense signaling pathways to channel plant energy into growth processes, but is
      required for normal levels of resistance against nematodes.

PMID- 18052888
TI  - Ubc2, an ortholog of the yeast Ste50p adaptor, possesses a basidiomycete-specific
      carboxy terminal extension essential for pathogenicity independent of pheromone
      response.
AB  - Proteins involved in the mitogen-activated protein (MAP) kinase pathway
      controlling mating, morphogenesis, and pathogenicity have been identified
      previously in the fungus Ustilago maydis. One of these, the Ubc2 adaptor protein,
      possesses a basidiomycete-specific structure. In addition to containing sterile
      alpha motif (SAM) and ras association (RA) domains typical of Ste50-like adaptor
      proteins found in the fungal phylum Ascomycota, Ubc2 also contains two C-terminal
      SH3 domains. Yeast two-hybrid assays indicated that Ubc2 interacts with the MAP
      kinase-kinase kinase Ubc4 via the SAM domains at each of their respective N
      termini. Site-directed mutagenesis of ubc2 and complementation analyses revealed
      that the SAM and RA domains of Ubc2 are essential for filamentous growth. These
      data support a role for the ascomycete-like N-terminus of Ubc2 in regulating
      pheromone-responsive mating and morphogenesis analogous to the role of Ste50p in
      Saccharomyces cerevisiae. In contrast, C-terminal deletion mutants were fully
      capable of filamentous growth and mating. However, surprisingly, these strains
      were nonpathogenic. Further, directed mutagenesis of the C-terminus revealed that
      both SH3 domains are required for pathogenicity. These results suggest that the
      Basidiomycota have retained the mating and morphogenetic functions of Ste50-type
      proteins in the N-terminal half of their Ubc2-type adaptors but, additionally,
      have integrated C-terminal SH3 domains that are critical for additional signal
      transduction mechanisms, including those that lead to pathogenesis.

PMID- 18052889
TI  - Responses of two contrasting genotypes of rice to brown planthopper.
AB  - Rice (Oryza sativa L.) and brown planthoppers (BPH) (Nilaparvata lugens Stal)
      provide an ideal system for studying molecular mechanisms involved in the
      interactions between plants and phloem-feeding insects. The phenotypic responses
      and changes in transcript profiles of seedlings representing two rice cultivars
      differing in resistance to the BPH were analyzed. In the BPH-compatible
      (susceptible) cv. MH63, BPH feeding reduced three examined plant growth
      parameters (leaf area expansion, height increases, and dry weight increases) and
      photosynthetic rates of the leaves. In the BPH-incompatible (resistant) cv. B5,
      BPH feeding caused slight reductions in protein and sucrose contents, but the
      plants maintained their photosynthetic activity and grew normally. A cDNA
      microarray containing 1,920 suppression subtractive hybridization clones was used
      to explore the transcript profiles differences in the two cultivars under control
      and BPH-feeding conditions. In total, 160 unique genes were detected as being
      significantly affected by BPH feeding in rice plants, covering a wide range of
      functional categories, and there were 38 genes that showed the similar transcript
      pattern in both genotypes. The physiological responses and transcript profiles of
      plants represented in both genotypes suggested that multiple pathways might be
      involved in reprogramming of BPH-infested rice plants. The differences in
      transcript levels between the compatible and incompatible interactions revealed
      in this study were not only the reaction of resistance and susceptibility but
      also reflections of different damage rates and genotypic backgrounds of the rice
      cultivars.

PMID- 18052890
TI  - Dynamic regulation of GacA in type III secretion, pectinase gene expression,
      pellicle formation, and pathogenicity of Dickeya dadantii (Erwinia chrysanthemi
      3937).
AB  - Dickeya dadantii (Erwinia chrysanthemi 3937) secretes exoenzymes, including
      pectin-degrading enzymes, leading to the loss of structural integrity of plant
      cell walls. A type III secretion system (T3SS) is essential for full virulence of
      this bacterium within plant hosts. The GacS/GacA two-component signal
      transduction system participates in important biological roles in several gram
      negative bacteria. In this study, a gacA deletion mutant (Ech137) of D. dadantii
      was constructed to investigate the effect of this mutation on pathogenesis and
      other phenotypes. Compared with wild-type D. dadantii, Ech137 had a delayed
      biofilm-pellicle formation. The production of pectate lyase (Pel), protease, and
      cellulase was diminished in Ech137 compared with the wild-type cells. Reduced
      transcription of two endo-Pel genes, pelD and pelL, was found in Ech137 using a
      green fluorescence protein-based fluorescence-activated cell sorter promoter
      activity assay. In addition, the transcription of T3SS genes dspE (an effector),
      hrpA (a structural protein of the T3SS pilus), and hrpN (a T3SS harpin) was
      reduced in Ech137. A lower amount of rsmB regulatory RNA was found in gacA mutant
      Ech137 compared with the wild-type bacterium by quantitative reverse
      transcription polymerase chain reaction. Compared with wild-type D. dadantii, a
      lower amount of hrpL mRNA was observed in Ech137 at 12 h grown in medium.
      Although the role of RsmA, rsmB, and RsmC in D. dadantii is not clear, from the
      regulatory pathway revealed in E. carotovora, the lower expression of dspE, hrpA,
      and hrpN in Ech137 may be due to a post-transcriptional regulation of hrpL
      through the Gac-Rsm regulatory pathway. Consequently, the reduced exoenzyme
      production and Pel gene expression in the mutant may be sue partially to the
      regulatory role of rsmB-RsmA on exoenzyme expression. Similar to in vitro
      results, a lower expression of T3SS and pectinase genes of Ech137 also was
      observed in bacterial cells inoculated into Saintpaulia ionantha leaves, perhaps
      accounting for the observed reduction in local maceration. Interestingly,
      compared with the wild-type D. dadantii, although a lower concentration of Ech137
      was observed at day 3 and 4 postinoculation, there is no significant difference
      in bacterial concentration between the wild-type bacterium and Ech137 in the
      early stage of infection. Finally, the nearly abolished systemic invasion ability
      of Ech137 suggests that GacA of D. dadantii is essential for the pathogenicity
      and systemic movement of the bacterium in S. ionantha.

PMID- 18052892
TI  - Managing acute heart failure in the intensive care unit.

PMID- 18052891
TI  - My tortuous journey to a life in interferon research.

PMID- 18052893
TI  - Echocardiography training for the intensivist.
AB  - The value of echocardiography in the critically ill patient is well established,
      yet applying the modality to patients who could benefit presents considerable
      logistical challenges. Central is a lack of readily available, trained operators.
      Although many intensive care specialists and trainees are keen to fill this gap,
      there are numerous hurdles to obtaining the necessary training. To address this
      problem, the Australian and New Zealand Intensive Care Society has set up a
      Committee on Echocardiography Training and Certification for Intensivists. The
      Committee proposes a formal training and assessment program. This would not only
      provide guidance to intensivists wishing to learn echocardiography, but also
      clearly set out acceptable levels of expertise. It is important that, after
      training, intensivists can be readily credentialed in their home institutions.
      The intensive care community needs to determine the vehicle for training and
      credentialling in echocardiography. This could be achieved solely by bodies
      representing intensive care or in collaboration with the Australasian Society for
      Ultrasound in Medicine.

PMID- 18052894
TI  - Managing risk to improve cardiac surgical outcomes.
AB  - Mortality and quality of cardiac surgery are inextricably linked. Mortality can
      be a suitable measure of the quality of the service as long as risk is taken into
      account, using one of a variety of available risk models. The measurement of risk
      adjusted mortality can provide the tools with which to improve cardiac surgical
      outcomes, as well as open up an exciting area of future study to identify where
      further improvements can be made.

PMID- 18052895
TI  - Long-stay patients in Australian and New Zealand intensive care units:
      demographics and outcomes.
AB  - AIM AND METHODS: There is no consensus definition on what constitutes a long stay
      in the intensive care unit, and little published information on the demographic
      characteristics, resource usage or outcomes of long-stay patients. We used data
      from the Australian and New Zealand Intensive Care Society Adult Patient Database
      to identify patients who had spent > 21 days in the ICU. We examined their
      resource usage, hospital type, diagnoses and outcomes, and trends in these
      characteristics over 5 years (2000-2004). RESULTS: 6,565 patients (2.3% of all
      ICU patients) had one or more admissions > 21 days and accounted for 23% of total
      ICU bed-hour usage. Long-stay patients had a mean (SD) age of 60.3 (15.3) years
      and an APACHE III-J risk of death of 32.7% (21.3%). Metropolitan and tertiary
      hospitals had the highest proportions of long-stay patients. The three diagnoses
      most strongly associated with long ICU stay were neuromuscular disease (odds
      ratio [OR], 13.3; 95% CI, 10.2-17.4; P < 0.001), burns (OR, 6.0; 95% CI, 4.9-7.3;
      P < 0.001) and cervical spine injury (OR, 5.1; 95% CI, 3.4-7.5; P < 0.001), while
      the most common diagnosis was pneumonia (12.7% of total). During the period 2000-
      2004, there was no significant change in the proportion, age, resource usage or
      outcomes of these patients. Overall observed mortality was 28% (predicted, 32.7%;
      95% CI, 31.4%-34.5%). Of those aged >or= 80 years, 37% were discharged home, and
      39% died. CONCLUSIONS: Patients who spend > 21 days in the ICU use significant
      resources but appear to have worthwhile outcomes in all age brackets.

PMID- 18052896
TI  - Mortality and outcomes of elderly patients admitted to the intensive care unit at
      Cairns Base Hospital, Australia.
AB  - OBJECTIVE: To determine the survival and outcome of elderly patients admitted to
      the intensive care unit at Cairns Base Hospital. METHODS: A retrospective review
      of patients aged 60 years or over admitted to the ICU (a Level 2 general unit) at
      Cairns Base Hospital, a regional hospital in Queensland, during 2003-2005.
      Mortality was determined by review of hospital records, the Queensland register
      of deaths, and direct patient or family contact in November 2006. Demographic and
      clinical details were collected, and the EuroQol-5D questionnaire was used to
      assess current and pre-ICU quality of life. RESULTS: 432 patients aged >or= 60
      years had 469 admissions to the ICU during 2003-2005. Long-term outcome was
      determined for 68%: 201 (46%) were confirmed dead, and 94 (22%) were confirmed
      alive, while the outcome for 137 (32%) remained unknown. Allowing for an
      estimated mortality of 39% in the unknown group, the overall estimated mortality
      was 60%. Mean follow-up time was 2.4 (SD, 0.9) years (range, 11-35 months). As
      age increased, mortality increased: 37% for the 60-70 years age group; 50% for 70
      80 years; 61% for 80-90 years, and 83% for > 90 years. The quality of life of
      survivors was lower on follow-up than on ICU admission. CONCLUSIONS: Elderly
      patients admitted to the ICU have high mortality. As age increases, mortality
      increases. Elderly survivors can expect a lower quality of life after an ICU
      admission, although on average the difference is not great.

PMID- 18052897
TI  - Atypical neuroleptic malignant syndrome with long-term clozapine.
AB  - Clozapine-induced neuroleptic malignant syndrome (NMS) may present differently
      from NMS associated with traditional antipsychotic agents, with fewer clinical
      features, particularly fewer extrapyramidal manifestations. The risk of
      developing NMS with clozapine does not appear dose-related. In half of cases, it
      occurs within 2 weeks of beginning clozapine therapy, but it can develop at any
      stage, especially with long-term use. We describe a patient who presented with
      atypical NMS after more than 10 years of clozapine treatment, and who was safely
      re-challenged with the same drug.

PMID- 18052898
TI  - Deep accidental hypothermia during the Queensland summer.
AB  - A 52-year-old woman presented with severe accidental hypothermia associated with
      out-of-hospital cardiac arrest after a polypharmacy overdose. Deep hypothermia
      developed while she lay unconscious, with a split-system air-conditioning unit
      rapidly cooling the confined area of her bedroom. Despite the need for lengthy
      resuscitative efforts at the scene and in hospital, she went on to a full
      neurological recovery. The neuroprotective role of accidental hypothermia is
      reviewed, as are the guidelines for resuscitation in this setting. We conclude
      that hypothermia must be considered even in unlikely circumstances, such as the
      Queensland summer, when ambient temperatures are high.

PMID- 18052899
TI  - The left heart can only be as good as the right heart: determinants of function
      and dysfunction of the right ventricle.
AB  - Discussions of cardiac physiology and pathophysiology most often emphasise the
      function of the left heart. However, right heart dysfunction plays an important
      role in critically ill patients and is often not recognised. This is probably
      because the role of the right ventricle is for generating flow more than
      pressure, and flow is not easy to evaluate. Of importance, when right ventricular
      function limits cardiac output, assessing left ventricular function gives little
      indication of overall cardiac performance. It has recently become evident that
      the right ventricle also has different genetic origins and characteristics from
      the left ventricle. The right and left ventricles interact through series
      effects, diastolic interactions and systolic interactions. The mechanisms of
      these, and their physiological and pathological significance are discussed.

PMID- 18052900
TI  - Catecholamines for shock: the quest for high-quality evidence.
AB  - Despite the established role of catecholamines for the treatment of circulatory
      shock in intensive care medicine, these drugs have been subjected to few
      randomised controlled trials with high methodological quality and patient-centred
      outcomes. The literature has been dominated by low-quality, case-control studies
      of the effects of synthetic catecholamines on surrogate haemodynamic end-points.
      A recent Cochrane systematic review of the effects of vasopressors on mortality
      from circulatory shock identified seven randomised controlled trials, none of
      which demonstrated any conclusive evidence of benefit of one inotrope/vasopressor
      over another. The review confirmed the persisting low methodological quality of
      these studies. Three higher-quality studies of catecholamines (noradrenaline,
      adrenaline, dopamine and vasopressin) have been completed, the results of which
      will provide some evidence of efficacy of catecholamines on mortality and
      resolution of shock. These studies may provide the basis for designing and
      conducting a large-scale, pragmatic, randomised controlled trial to analyse the
      effects of these commonly used drugs on patient-centred outcomes, such as
      mortality, resolution of organ failure and hospital length of stay. The results
      of such a study would be particularly important in geographical regions where
      access to inotropes/vasopressors other than adrenaline remains restricted.

PMID- 18052901
TI  - Thrombolysis is not warranted in submassive pulmonary embolism: a systematic
      review and meta-analysis.
AB  - Acute pulmonary embolism (PE) is a major cause of morbidity and mortality in
      hospitalised patients. While the vast majority of patients with PE survive, a
      subset die, mostly within a few hours of presentation. Anatomically massive
      pulmonary emboli account for only half these deaths, while submassive or
      recurrent embolism accounts for the other half. There are increasing reports of
      patients with PE, normal blood pressure and no shock who have significant right
      heart dysfunction. In large registry-based cohorts, patients with right
      ventricular dysfunction have worse clinical outcomes. Rapid anticoagulation of
      the haemodynamically stable patient with PE is associated with excellent
      outcomes. There is also evidence to support the use of thrombolysis in patients
      with massive PE. However, the optimal management of patients with submassive PE
      is controversial. This article looks at the definition and diagnosis of
      submassive PE, and systematically reviews the role of thrombolytic therapy in
      this subgroup of patients.

PMID- 18052902
TI  - "Don't flog the heart!" - development of specific drug therapies for heart
      failure.
AB  - Understanding the cellular and molecular biology of heart failure is essential to
      developing targeted and effective treatment. Investigators are divided in their
      belief regarding the primary abnormality and whether it lies in dysregulation of
      neurohormonal signalling; nitric oxide synthesis and oxidative stress; cellular
      energy supply; or cellular ions. Our research demonstrates that these
      independently studied pathways are, in fact, closely interrelated. The Na+-K+
      pump is critical in the determination of intracellular sodium levels, which are
      elevated in heart failure. Drug therapies have been developed targeting the
      neurohormonal abnormalities seen in the clinical syndrome of heart failure. We
      have examined the effect of many of these medications on the activity of the Na+
      K+ pump and observed a perfect correlation between the ability of the treatment
      to stimulate the pump and its clinical outcome. This is illustrated by the
      stimulation of the pump by inhibition of the renin- angiotensin signalling
      pathway, and by aldosterone antagonists. We have also examined the role of
      reactive oxygen species as mediators of angiotensin and adrenergic regulation of
      the pump, demonstrating that intracellular pathways activated by Beta(1)/Beta(2)
      adrenoceptors and the angiotensin II type 1 receptor converge, with both
      activating NAD(P)H oxidase and inhibiting the Na+-K+ pump via oxidative stress.
      In contrast, targeted stimulation of the Beta(3)-receptor resulted in nitric
      oxide-dependent pump stimulation in vitro, and improvements in left ventricular
      function in a large-animal heart failure model. Further characterisation of the
      intricate pathways involved in the hormonal regulation of the myocyte and its
      response to heart failure may aid in specific targeting of therapy.

PMID- 18052903
TI  - Percutaneous coronary intervention in the 21st century - making surgeons
      irrelevant?
AB  - Interventional cardiology is a rapidly changing area, with technical improvements
      allowing us to treat an increasing number of clinical situations by percutaneous
      methods. Indeed, the interface between interventional cardiologist and cardiac
      surgeon has changed in the past decade, with a dramatic reduction in the need for
      "rescue" surgery. The most significant recent development has been drug-eluting
      stents, which have dramatically reduced the rates of restenosis, although at the
      cost of a need for longer-term antiplatelet therapy after implantation. Failure
      to continue this antiplatelet therapy may lead to a small but significant excess
      of stent thrombosis. There have been many other technological improvements, such
      as distal protection devices and better guidewires for crossing occluded vessels,
      as well as percutaneous devices for treating valve disease and other structural
      cardiac abnormalities. These technologies are often best developed in a combined
      approach with cardiac surgeons, and the selection of the best treatment more than
      ever requires close cooperation between cardiologist and surgeon.

PMID- 18052904
TI  - Should doctors keep calling medicines "drugs"?

PMID- 18052905
TI  - 19th century pioneers of intensive therapy in North America. Part 1: George
      Edward Fell.
AB  - For three decades after Marshall Hall's 1856 strictures against "forcing methods"
      and bellows for artificial ventilation (AV), human "forced respiration"
      (equivalent to intermittent positive pressure ventilation) was virtually
      abandoned. Various arm-chest manoeuvres often proved inadequate to save life.
      After doctor and engineer George Fell, of Buffalo (New York) (1849-1918), failed
      to save the life of an opiate-poisoned patient using Silvester's popular method,
      he resolved to try his animal laboratory AV method (bellows and tracheotomy).
      Following his first success in a landmark case (1887), he better adapted the
      apparatus for human use and soon succeeded with further difficult cases, but was
      unable to raise enthusiasm for his "Fell method" of AV. His reports of successful
      rescues to prestigious Washington Congresses met derision (1887) and indifference
      (1893), although by then they detailed 28 "human lives saved", mostly after
      opiate poisoning, and a switch from tracheotomies to face masks (simpler, but
      with a few complications). Continuing with rescues throughout the 1890s, Fell
      personally achieved recoveries after AV for as long as 73.5 hours (1896), and
      over 78 hours (1899). He argued for his method repeatedly with many talks, much
      documentation, and pleas for its use in other ventilatory crises. Despite his
      endeavours and successes, Fell was unable to secure widespread uptake of forced
      respiration, but others adopted his principles. Joseph O'Dwyer modified Fell's
      face mask-tracheotomy system by incorporating an intralaryngeal tube, and this
      "Fell-O'Dwyer apparatus" was used for neurosurgical cases (1894), also
      revolutionising intrathoracic surgery (1899).

PMID- 18052906
TI  - Is there a place for levosimendan in the intensive care unit?

PMID- 18052909
TI  - Testing for trends in dose-response microarray experiments: a comparison of
      several testing procedures, multiplicity and resampling-based inference.
AB  - Dose-response studies are commonly used in experiments in pharmaceutical research
      in order to investigate the dependence of the response on dose, i.e., a trend of
      the response level toxicity with respect to dose. In this paper we focus on dose
      response experiments within a microarray setting in which several microarrays are
      available for a sequence of increasing dose levels. A gene is called
      differentially expressed if there is a monotonic trend (with respect to dose) in
      the gene expression. We review several testing procedures which can be used in
      order to test equality among the gene expression means against ordered
      alternatives with respect to dose, namely Williams' (Williams 1971 and 1972),
      Marcus' (Marcus 1976), global likelihood ratio test (Bartholomew 1961, Barlow et
      al. 1972, and Robertson et al. 1988), and M (Hu et al. 2005) statistics.
      Additionally we introduce a modification to the standard error of the M
      statistic. We compare the performance of these five test statistics. Moreover, we
      discuss the issue of one-sided versus two-sided testing procedures. False
      Discovery Rate (Benjamni and Hochberg 1995, Ge et al. 2003), and resampling-based
      Familywise Error Rate (Westfall and Young 1993) are used to handle the multiple
      testing issue. The methods above are applied to a data set with 4 doses (3 arrays
      per dose) and 16,998 genes. Results on the number of significant genes from each
      statistic are discussed. A simulation study is conducted to investigate the power
      of each statistic. A R library IsoGene implementing the methods is available from
      the first author.

PMID- 18052910
TI  - On the operational characteristics of the Benjamini and Hochberg False Discovery
      Rate procedure.
AB  - Multiple testing procedures are commonly used in gene expression studies for the
      detection of differential expression, where typically thousands of genes are
      measured over at least two experimental conditions. Given the need for powerful
      testing procedures, and the attendant danger of false positives in multiple
      testing, the False Discovery Rate (FDR) controlling procedure of Benjamini and
      Hochberg (1995) has become a popular tool. When simultaneously testing
      hypotheses, suppose that R rejections are made, of which Fp are false positives.
      The Benjamini and Hochberg procedure ensures that the expectation of Fp/R is
      bounded above by some pre-specified proportion. In practice, the procedure is
      applied to a single experiment. In this paper we investigate the across
      experiment variability of the proportion Fp/R as a function of three experimental
      parameters. The operational characteristics of the procedure when applied to
      dependent hypotheses are also considered.

PMID- 18052911
TI  - A comparison of methods to control type I errors in microarray studies.
AB  - Microarray studies often need to simultaneously examine thousands of genes to
      determine which are differentially expressed. One main challenge in those studies
      is to find suitable multiple testing procedures that provide accurate control of
      the error rates of interest and meanwhile are most powerful, that is, they return
      the longest list of truly interesting genes among competitors. Many multiple
      testing methods have been developed recently for microarray data analysis,
      especially resampling based methods, such as permutation methods, the null
      centered and scaled bootstrap (NCSB) method, and the quantile-transformed
      bootstrap-distribution (QTBD) method. Each of these methods has its own merits
      and limitations. Theoretically permutation methods can fail to provide accurate
      control of Type I errors when the so-called subset pivotality condition is
      violated. The NCSB method does not suffer from that limitation, but an
      impractical number of bootstrap samples are often needed to get proper control of
      Type I errors. The newly developed QTBD method has the virtues of providing
      accurate control of Type I errors under few restrictions. However, the relative
      practical performance of the above three types of multiple testing methods
      remains unresolved. This paper compares the above three resampling based methods
      according to the control of family wise error rates (FWER) through data
      simulations. Results show that among the three resampling based methods, the QTBD
      method provides relatively accurate and powerful control in more general
      circumstances.

PMID- 18052912
TI  - Selection of biologically relevant genes with a wrapper stochastic algorithm.
AB  - We investigate an important issue of a meta-algorithm for selecting variables in
      the framework of microarray data. This wrapper method starts from any
      classification algorithm and weights each variable (i.e. gene) relative to its
      efficiency for classification. An optimization procedure is then inferred which
      exhibits important genes for the studied biological process. Theory and
      application with the SVM classifier were presented in Gadat and Younes, 2007 and
      we extend this method with CART. The classification error rates are computed on
      three famous public databases (Leukemia, Colon and Prostate) and compared with
      those from other wrapper methods (RFE, lo norm SVM, Random Forests). This allows
      the assessment of the statistical relevance of the proposed algorithm.
      Furthermore, a biological interpretation with the Ingenuity Pathway Analysis
      software outputs clearly shows that the gene selections from the different
      wrapper methods raise very relevant biological information, compared to a
      classical filter gene selection with T-test.

PMID- 18052913
TI  - T-BAPS: a Bayesian statistical tool for comparison of microbial communities using
      terminal-restriction fragment length polymorphism (T-RFLP) data.
AB  - The investigation of microbial communities is an essential part of the study of
      the biosphere. Flexible molecular fingerprinting tools such as terminal
      restriction fragment length polymorphism (T-RFLP) analysis are often applied in
      the studies to enable the characterization of the microbial population. However,
      such data have so far been primarily analyzed using conventional clustering
      methods. Here we introduce a Bayesian model-based method for the purpose of
      comparing microbial communities using T-RFLP data. Such datasets have in general
      several challenging features, e.g. sparseness, missing values and structurally
      zero-valued observations. These features are taken into account by developing a
      Bayesian latent class mixture model for the observations in our framework. To
      make inferences under the model we use a recent Markov chain Monte Carlo (MCMC) 
      based method for the Bayesian model selection. To assess the introduced method we
      analyze both simulated and real datasets. The simulations show that our approach
      compares preferably to standard statistical clustering tools, such as k-means,
      hierarchical clustering, and Autoclass. The developed tool is freely available as
      a software package T-BAPS at http://www.abo.fi/fak/mnf/mate/jc/software/t
      baps.html.

PMID- 18052914
TI  - Population structure and covariate analysis based on pairwise microsatellite
      allele matching frequencies.
AB  - We describe a general model for pairwise microsatellite allele matching
      probabilities. The model can be used for analysis of population substructure, and
      is particularly focused on relating genetic correlation to measurable covariates.
      The approach is intended for cases when the existence of subpopulations is
      uncertain and a priori assignment of samples to hypothesized subpopulations is
      difficult. Such a situation arises, for example, with western Arctic bowhead
      whales, where genetic samples are available only from a possibly mixed migratory
      assemblage. We estimate genetic structure associated with spatial, temporal, or
      other variables that may confound the detection of population structure. In the
      bowhead case, the model permits detection of genetic patterns associated with a
      temporally pulsed multi-population assemblage in the annual migration. Hypothesis
      tests for population substructure and for covariate effects can be carried out
      using permutation methods. Simulated and real examples illustrate the
      effectiveness and reliability of the approach and enable comparisons with other
      familiar approaches. Analysis of the bowhead data finds no evidence for two
      temporally pulsed subpopulations using the best available data, although a
      significant pattern found by other researchers using preliminary data is also
      confirmed here. Code in the R language is available from
      www.stat.colostate.edu/~geof/gammmp.html.

PMID- 18052915
TI  - Estimating the arm-wise false discovery rate in array comparative genomic
      hybridization experiments.
AB  - Array Comparative Genomic Hybridization (aCGH) is an array-based technology which
      provides simultaneous spot assays of relative genetic abundance (RGA) levels at
      multiple sites across the genome. These spot assays are spatially correlated with
      respect to genomic location and, as a result, the univariate tests conducted
      using data generated from these spot assays are also spatially correlated. In the
      context of multiple hypothesis testing, this spatial correlation complicates the
      question of how best to define a 'discovery' and consequently, how best to
      estimate the false discovery rate (FDR) corresponding to a given rejection
      region. One can quantify the number of discoveries as the total number of spots
      for which the spot-based univariate test statistic falls within a given rejection
      region. Under this spot-based method, separate but correlated discoveries are
      identified. We show via a simulation study that the method of Benjamini and
      Hochberg (1995) can provide a reasonable estimate of the spot-wise FDR, but these
      results require that the simulated spot assays are categorized as true or false
      discoveries in a particular way. However, laboratory researchers may actually be
      interested in estimating a 'regional' FDR, rather than a 'local' spot-wise FDR.
      We describe an example of such circumstances, and present a method for estimating
      the (chromosome) arm-wise False Discovery Rate. In this framework, one can
      quantify the number of discoveries as the total number of chromosome arms for
      which at least one spot-based test statistic falls into a given rejection region.
      Defining the discoveries in this way, both the biological and testing objectives
      coincide. We provide results from a series of simulations which involved the
      analysis of preferentially re-sampled spot assay values from a real aCGH dataset.

PMID- 18052917
TI  - Preceptorship and mentorship: not merely a matter of semantics.
AB  - In academic writing on mentoring and preceptorship there is little consensus on
      the meaning or characteristics surrounding these terms. The writers of this paper
      contend that the correct usage of preceptorship and mentorship, which gives
      credence and respect to the very different concepts embedded in each, is a very
      important precursor to the evolution of these two concepts in nursing education,
      both academically and within practical application. Although language is
      continually changing, lack of clarity robs language of its richness and
      complexity and interferes with clear thinking about the issues. In professional
      terms, clarity demands that concepts, around which a body of knowledge is
      growing, be consistent in their meaning and characteristics. Such clarity between
      the related educational concepts of mentor(ship) and preceptor(ship) is lacking.

PMID- 18052916
TI  - An expectation maximization approach to estimate malaria haplotype frequencies in
      multiply infected children.
AB  - Characterizing genetic variability in the human pathogenic Plasmodium species,
      the group of parasites that cause Malaria, may have broad global health
      implications. Specifically, discerning the combinations of mutations that lead to
      viable parasites and the population level frequencies of these clonal sequences
      will allow for targeted vaccine development and individualized treatment choices.
      This presents an analytical challenge, however, since haplotypic phase (i.e. the
      alignment of bases on a single DNA strand) is generally unobservable in multiply
      infected individuals. This manuscript describes an expectation maximization (EM)
      approach to maximum likelihood estimation of haplotype frequencies in this
      missing data setting. The approach is applied to a cohort of N=341 malaria
      infected children in Uganda, Cameroon and Sudan to characterize regional
      differences. A simulation study is also presented to characterize method
      performance and assess sensitivity to distributional assumptions.

PMID- 18052918
TI  - Art as a scaffolding teaching strategy in baccalaureate nursing education.
AB  - Although the use of art in nursing education is well highlighted, most of the
      literature is anecdotal or focuses on development of a reflective nursing
      practice with clients. In this study, art was used as a scaffold to infuse
      liberal nursing education by helping baccalaureate nursing students (n = 91)
      create a personal expression of nursing and move toward greater self-awareness.
      Scaffolding is a metaphor for supporting learners as they develop higher levels
      of thinking. Using naturalistic inquiry to analyze students' written responses in
      a course activity, four themes emerged from the data: art and creativity,
      teamwork, boundaries and horizons within self, and boundaries and horizons in the
      profession. Student's individual expressions of art served as the "calling forth"
      of processes that opened the door to each student's personal expression.

PMID- 18052919
TI  - Improving preceptor self-efficacy using an online educational program.
AB  - The purpose of this study was to evaluate the effectiveness of a public/community
      health online preceptor education program on knowledge of the preceptor role and
      self-efficacy to perform in the preceptor role. Forty-eight public/community
      health nurses from five states completed an online education program, a 32-item
      quiz and a preceptor self-efficacy instrument. Preceptor self-efficacy and
      knowledge scores improved significantly after completing the online education
      program compared to pretest scores. Previous experience as a preceptor, age, and
      place of employment, were not correlated with preceptor self-efficacy scores.
      Previous preceptor education and highest level of education completed were
      positively correlated with preceptor self-efficacy scores. Previous preceptor
      education was reported by 39.6% of nurses. However, there was no standard
      curriculum for these education programs. The results of this study support the
      use of online education as a method for enhancing preceptor knowledge and
      confidence in the preceptor role.

PMID- 18052920
TI  - A comparison of clinical simulation and case study presentation on nurse
      practitioner students' knowledge and confidence in managing a cardiac event.
AB  - The study was designed to compare the efficacy of controlled simulation mannequin
      (SM) assisted learning and case study presentation on knowledge and confidence of
      nurse practitioner (NP) students in managing a cardiac event. Twenty-three
      volunteer students were randomly assigned to the experimental (simulation) or
      control (case study presentation) group. All participants were instructed on
      atrial arrhythmias, were pre- and post-tested on knowledge and confidence, and
      completed an evaluation of the experience. There were no statistically
      significant differences in knowledge test scores, although the control group
      scored significantly higher on post- test confidence (p=.040). Both groups rated
      their experience as valuable. The simulation and case study presentation had
      similar outcomes. Additional research is needed to determine the effectiveness of
      this teaching modality.

PMID- 18052921
TI  - Psychometric properties of the Chinese leadership practices inventory.
AB  - There is little evidence of psychometric properties of the Leadership Practices
      Inventory (LPI) when used with Taiwan's nursing faculty. The purpose of this
      study was to examine psychometric properties of the Chinese LPI and provide a
      culturally appropriate instrument for use in Taiwan's nursing. Thirteen bachelor
      and nine associate degree nursing programs were eligible for participation. The
      Chinese LPI was used to gather nursing faculty's perceptions of leadership
      behaviors of nursing deans and directors. A total of 369 questionnaires were
      returned. Psychometric examinations used content validity, internal consistency
      reliability, item analysis, and construct and concurrent validities. Cronbach's
      alpha of the Chinese LPI total scale was .96. Three factors were extracted that
      explained 59.5 % of the variance. Concurrent validity was supported by the
      Chinese Multifactor Leadership Questionnaire (MLQ-5X). Findings for the
      psychometric properties and cultural appropriateness of the Chinese LPI supported
      its potential as an instrument for measuring nursing leadership in Taiwan.

PMID- 18052922
TI  - Measures of homophobia among nursing students and faculty: a Midwestern
      perspective.
AB  - It is well documented that homophobia exists among healthcare providers including
      nurses. However, little research is available on the level of homophobia among
      nursing students and nursing faculty. Using the Index of Attitudes Toward
      Homosexuals (IAH) and the Homophobic Behavior of Students Scale (HBSS) 241
      nursing students and 32 faculty in a Midwest university were invited to
      participate. One hundred twenty six students completed the survey resulting in a
      51% return rate. Fifteen faculty completed the survey. Results reveal that there
      is a low level of homophobia among students and faculty at this university.
      Religion and LGBT acquaintances or family members accounted for most of the
      variance within the homophobia scores. While scores reflect low levels of
      homophobia, it is the belief of these researchers that they actually may reflect
      ambivalent or heterosexist attitudes toward LGBT people which may impact
      healthcare delivered by these future nurses.

PMID- 18052923
TI  - The functional relationship between co-repressor N-CoR and SMRT in mediating
      transcriptional repression by thyroid hormone receptor alpha.
AB  - A central issue in mediating repression by nuclear hormone receptors is the
      distinct or redundant function between co-repressors N-CoR (nuclear receptor co
      repressor) and SMRT (silencing mediator of retinoid and thyroid hormone
      receptor). To address the functional relationship between SMRT and N-CoR in TR
      (thyroid hormone receptor)-mediated repression, we have identified multiple TR
      target genes, including BCL3 (B-cell lymphoma 3-encoded protein), Spot14 (thyroid
      hormone-inducible hepatic protein), FAS (fatty acid synthase), and ADRB2 (beta
      adrenergic receptor 2). We demonstrated that siRNA (small interfering RNA)
      treatment against either N-CoR or SMRT is sufficient for the de-repression of
      multiple TR target genes. By the combination of sequence mining and physical
      association as determined by ChIP (chromatin immunoprecipitation) assays, we
      mapped the putative TREs (thyroid hormone response elements) in BCL3, Spot14, FAS
      and ADRB2 genes. Our data clearly show that SMRT and N-CoR are independently
      recruited to various TR target genes. We also present evidence that
      overexpression of N-CoR can restore repression of endogenous genes after knocking
      down SMRT. Finally, unliganded, co-repressor-free TR is defective in repression
      and interacts with a co-activator, p300. Collectively, these results suggest that
      both SMRT and N-CoR are limited in cells and that knocking down either of them
      results in co-repressor-free TR and consequently de-repression of TR target
      genes.

PMID- 18052924
TI  - First evidence of the pore-forming properties of a keratin from skin mucus of
      rainbow trout (Oncorhynchus mykiss, formerly Salmo gairdneri).
AB  - The epidermis of fish is covered with a layer of mucus, which contributes to the
      defence of the species against parasites, bacteria and fungi. We have previously
      extracted glycoproteins from various mucus samples from fish and have shown that
      they present pore-forming activities well correlated with strong antibacterial
      properties [Ebran, Julien, Orange, Saglio, Lemaitre and Molle(2000) Biochim.
      Biophys. Acta 1467, 271-280]. The present study focuses on the 65 kDa
      glycoprotein, Tr65, from the rainbow trout (Oncorhynchus mykiss, formerly Salmo
      gairdneri).Enzymatic digestion of Tr65 yielded a fragment pattern with strong
      homology with that of trout type II cytokeratin. Sequence analysis of the cDNA
      clone obtained by PCR confirmed this homology. We thus constructed a plasmid to
      overproduce the recombinant Tr65. We extracted and purified this recombinant
      Tr65, using it for multichannel and single-channel experiments in azolectin
      bilayers. Our results with recombinant Tr65 confirmed the pore-forming properties
      already shown with native antibacterial Tr65. These findings offer new insights
      into the function of keratin proteins present in various mucosal surfaces of
      animals and human beings.

PMID- 18052925
TI  - Fish oil fatty acids improve postprandial vascular reactivity in healthy men.
AB  - Chronic fish oil intervention had been shown to have a positive impact on
      endothelial function. Although high-fat meals have often been associated with a
      loss of postprandial vascular reactivity, studies examining the effects of fish
      oil fatty acids on vascular function in the postprandial phase are limited. The
      aim of the present study was to examine the impact of the addition of fish oil
      fatty acids to a standard test meal on postprandial vascular reactivity. A total
      of 25 men received in a random order either a placebo oil meal (40 g of mixed
      fat; fatty acid profile representative of the U.K. diet) or a fish oil meal (31 g
      of mixed fat and 9 g of fish oil) on two occasions. Vascular reactivity was
      measured at baseline (0 h) and 4 h after the meal by laser Doppler iontophoresis,
      and blood samples were taken for the measurement of plasma lipids, total nitrite,
      glucose and insulin. eNOS (endothelial NO synthase) and NADPH oxidase gene
      expression were determined in endothelial cells after incubation with TRLs
      (triacylglycerol-rich lipoproteins) isolated from the plasma samples taken at 4
      h. Compared with baseline, sodium nitroprusside (an endothelium-independent
      vasodilator)-induced reactivity (P=0.024) and plasma nitrite levels (P=0.001)
      were increased after the fish oil meal. In endothelial cells, postprandial TRLs
      isolated after the fish oil meal increased eNOS and decreased NADPH oxidase gene
      expression compared with TRLs isolated following the placebo oil meal (P</=0.03).
      In conclusion, meal fatty acids appear to be an important determinant of vascular
      reactivity, with fish oils significantly improving postprandial endothelium
      independent vasodilation.

PMID- 18052926
TI  - Unsaturated lipid peroxidation-derived aldehydes activate autophagy in vascular
      smooth-muscle cells.
AB  - Proteins modified by aldehydes generated from oxidized lipids accumulate in cells
      during oxidative stress and are commonly detected in diseased or aged tissue. The
      mechanisms by which cells remove aldehyde-adducted proteins, however, remain
      unclear. Here, we report that products of lipid peroxidation such as 4-HNE (4
      hydroxynonenal) and acrolein activate autophagy in rat aortic smooth-muscle cells
      in culture. Exposure to 4-HNE led to the modification of several proteins, as
      detected by anti-protein-4-HNE antibodies or protein-bound radioactivity in [3H]4
      HNE-treated cells. The 4-HNE-modified proteins were gradually removed from cells.
      The removal of 4-HNE-modified proteins was not affected by the oxidized protein
      hydrolase inhibitor, acetyl leucine chloromethyl ketone, or lactacystin, although
      it was significantly decreased by PSI (proteasome inhibitor I), the
      lysosome/proteasome inhibitor MG-132 (carbobenzoxy-L-leucyl-L-leucyl-leucinal),
      insulin or the autophagy inhibitor 3-MA (3-methyladenine). Pre-incubation of
      cells with rapamycin accelerated the removal of 4-HNE-modified proteins.
      Treatment with 4-HNE, nonenal and acrolein, but not nonanal or POVPC (1-palmitoyl
      2-oxovaleroyl phosphatidyl choline), caused a robust increase in LC3-II
      (microtubule-associated protein 1 light chain 3-II) formation, which was
      increased also by rapamycin, but prevented by insulin. Electron micrographs of 4
      HNE-treated cells showed extensive vacuolization, pinocytic body formation,
      crescent-shaped phagophores, and multilamellar vesicles. Treatment with 3-MA and
      MG-132, but not proteasome-specific inhibitors, induced cell death in 4-HNE
      treated cells. Collectively, these results show that lipid peroxidation-derived
      aldehydes stimulate autophagy, which removes aldehyde-modified proteins, and that
      inhibition of autophagy precipitates cell death in aldehyde-treated cells.
      Autophagy may be an important mechanism for the survival of arterial smooth
      muscle cells under conditions associated with excessive lipid peroxidation.

PMID- 18052927
TI  - A decrease in cellular energy status stimulates PERK-dependent eIF2alpha
      phosphorylation and regulates protein synthesis in pancreatic beta-cells.
AB  - In the present study, we demonstrate that, in pancreatic beta-cells, eIF2alpha
      (eukaryotic initiation factor 2alpha) phosphorylation in response to a decrease
      in glucose concentration is primarily mediated by the activation of PERK [PKR
      (protein kinase RNA activated)-like endoplasmic reticulum kinase]. We provide
      evidence that this increase in PERK activity is evoked by a decrease in the
      energy status of the cell via a potentially novel mechanism that is independent
      of IRE1 (inositol requiring enzyme 1) activation and the accumulation of unfolded
      nascent proteins within the endoplasmic reticulum. The inhibition of eIF2alpha
      phosphorylation in glucose-deprived cells by the overexpression of dominant
      negative PERK or an N-terminal truncation mutant of GADD34 (growth-arrest and DNA
      damage-inducible protein 34) leads to a 53% increase in the rate of total protein
      synthesis. Polysome analysis revealed that this coincides with an increase in the
      amplitude but not the number of ribosomes per mRNA, indicating that eIF2alpha
      dephosphorylation mobilizes hitherto untranslated mRNAs on to polysomes. In
      summary, we show that PERK is activated at low glucose concentrations in response
      to a decrease in energy status and that this plays an important role in glucose
      regulated protein synthesis in pancreatic beta-cells.

PMID- 18052928
TI  - In nucleoli, the steady state of nucleolar proteins is leptomycin B-sensitive.
AB  - BACKGROUND INFORMATION: The nucleolus is a dynamic structure. It has been
      demonstrated that nucleolar proteins rapidly associate with and dissociate from
      nucleolar components in continuous exchanges with the nucleoplasm using GFP
      (green fluorescent protein)-tagged proteins. However, how the exchanges within
      one nucleolus and between nucleoli within the nuclear volume occurred is still
      poorly understood. RESULTS: The movement of PAGFP (photoactivatable GFP)-tagged
      proteins that become visible after photoactivation can be followed. In the
      present study, we establish the protocol allowing quantification of the traffic
      of PAGFP-tagged nucleolar proteins in nuclei containing two nucleoli. The traffic
      in the activated area, at the periphery of the activated area and to the
      neighbouring nucleolus is measured. Protein B23 is rapidly replaced in the
      activated area, and at the periphery of the activated area the steady state
      suggests intranucleolar recycling of B23; this recycling is LMB (leptomycin B)
      sensitive. The pool of activated B23 is equally distributed in the volume of the
      two nucleoli within 2 min. The three-dimensional distribution of the proteins
      Nop52 and fibrillarin is less rapid than that of B23 but is also LMB-sensitive.
      In contrast, traffic of fibrillarin from the nucleoli to the CB (Cajal body) was
      not modified by LMB. CONCLUSIONS: We propose that the steady state of nucleolar
      proteins in nucleoli depends on the affinity of the proteins for their partners
      and on intranucleolar recycling. This steady state can be impaired by LMB but not
      the uptake in the neighbouring nucleolus or the CB.

PMID- 18052929
TI  - Purification and properties of the alkaline lipase from Burkholderia cepacia
      A.T.C.C. 25609.
AB  - A Burkholderia cepacia (bacteria) strain, A.T.C.C. 25609, which had been isolated
      from the bronchial washings of a cystic fibrosis patient, was used to produce
      lipase. The presence of sodium alginate at an optimal concentration of 8 mg.ml(
      1) in the growth medium nearly doubled the production of extracellular lipase
      activity. The enzyme could be purified with 38-fold purification and 96% activity
      recovery using a two-step purification protocol. The molecular mass of the
      purified lipase determined by SDS/PAGE was shown to be 28 kDa. The pH optimum of
      the purified enzyme was 9 and it was stable up to 12 h at pH 9 and 10. The enzyme
      has a temperature optimum of 40 degrees C and its half-life (t(1/2)) values were
      54 and 46 min at 50 and 60 degrees C respectively. The lipase was found to be
      stable in the presence of the detergents Tween 20 and Triton X-100. The secondary
      structure analysis of lipase by CD spectroscopy showed 52% alpha-helix, 7.7% beta
      sheet, 12.6% beta-turn and 27.8% random structure. The lipase was cloned and
      overexpressed in Escherichia coli. The gene sequence of the cloned lipase was
      determined and compared with other lipases.

PMID- 18052930
TI  - Peroxiredoxin IV is an endoplasmic reticulum-localized enzyme forming oligomeric
      complexes in human cells.
AB  - The peroxiredoxins are a ubiquitous family of proteins involved in protection
      against oxidative stress through the detoxification of cellular peroxides. In
      addition, the typical 2-Cys peroxiredoxins function in signalling of peroxide
      stress and as molecular chaperones, functions that are influenced by their
      oligomeric state. Of the human peroxiredoxins, Prx IV (peroxiredoxin IV) is
      unique in possessing an N-terminal signal peptide believed to allow secretion
      from the cell. Here, we present a characterization of Prx IV in human cells
      demonstrating that it is actually retained within the ER (endoplasmic reticulum).
      Stable knockdown of Prx IV expression led to detrimental effects on the viability
      of human HT1080 cells following treatment with exogenous H2O2. However, these
      effects were not consistent with a dose-dependent correlation between Prx IV
      expression and peroxide tolerance. Moreover, modulation of Prx IV expression
      showed no obvious effect on ER-associated stress, redox conditions or H2O2
      turnover. Subsequent investigation demonstrated that Prx IV forms complex
      structures within the ER, consistent with the formation of homodecamers.
      Furthermore, Prx IV oligomeric interactions are stabilized by additional non
      catalytic disulfide bonds, indicative of a primary role other than peroxide
      elimination.

PMID- 18052931
TI  - Enhanced cell-surface stability of rescued DeltaF508 cystic fibrosis
      transmembrane conductance regulator (CFTR) by pharmacological chaperones.
AB  - Misfolded proteins destined for the cell surface are recognized and degraded by
      the ERAD [ER (endoplasmic reticulum) associated degradation] pathway. TS
      (temperature-sensitive) mutants at the permissive temperature escape ERAD and
      reach the cell surface. In this present paper, we examined a TS mutant of the
      CFTR [CF (cystic fibrosis) transmembrane conductance regulator], CFTR DeltaF508,
      and analysed its cell-surface trafficking after rescue [rDeltaF508 (rescued
      DeltaF508) CFTR]. We show that rDeltaF508 CFTR endocytosis is 6-fold more rapid
      (approximately 30% per 2.5 min) than WT (wild-type, approximately 5% per 2.5 min)
      CFTR at 37 degrees C in polarized airway epithelial cells (CFBE41o-). We also
      investigated rDeltaF508 CFTR endocytosis under two further conditions: in culture
      at the permissive temperature (27 degrees C) and following treatment with
      pharmacological chaperones. At low temperature, rDeltaF508 CFTR endocytosis
      slowed to WT rates (20% per 10 min), indicating that the cell-surface trafficking
      defect of rDeltaF508 CFTR is TS. Furthermore, rDeltaF508 CFTR is stabilized at
      the lower temperature; its half-life increases from <2 h at 37 degrees C to >8 h
      at 27 degrees C. Pharmacological chaperone treatment at 37 degrees C corrected
      the rDeltaF508 CFTR internalization defect, slowing endocytosis from
      approximately 30% per 2.5 min to approximately 5% per 2.5 min, and doubled
      DeltaF508 surface half-life from 2 to 4 h. These effects are DeltaF508 CFTR
      specific, as pharmacological chaperones did not affect WT CFTR or transferrin
      receptor internalization rates. The results indicate that small molecular
      correctors may reproduce the effect of incubation at the permissive temperature,
      not only by rescuing DeltaF508 CFTR from ERAD, but also by enhancing its cell
      surface stability.

PMID- 18052932
TI  - Bioengineering functional human aortic vascular smooth-muscle strips in vitro.
AB  - The contraction and relaxation of VSM (vascular smooth muscle) are responsible
      for the maintenance of vascular tone, which is a major determinant of blood
      pressure. However, the molecular events leading to the contraction and relaxation
      of VSM are poorly understood. The development of three-dimensional bioengineered
      tissues provides an opportunity to investigate the molecular events controlling
      vascular tone in vitro. In the present study we used fibrin-gel casting to
      bioengineer functional VSM strips from primary human aortic VSM cells. Our
      bioengineered VSM strips are functionally similar to VSM in vivo and remained
      viable in culture for up to 5 weeks. VSM strips demonstrate spontaneous basal
      tone and can generate an active force (contraction) of up to 85.2 microN on
      stimulation with phenylephrine. Bioengineered VSM strips exhibited Ca(2+)
      dependent contraction and calcium-independent relaxation. The development of
      functional bioengineered VSM tissue provides a new in vitro model system that can
      be used to investigate the molecular events controlling vascular tone.

PMID- 18052933
TI  - Application of SCAR (sequence characterized amplified region) analysis to
      authenticate Lycium barbarum (wolfberry) and its adulterants.
AB  - Fructus Lycii (Gouqizi) is well known in Chinese herbal medicine for its
      restorative function of benefiting the liver and kidney, replenishing vital
      essence and improving eyesight. However, ten species and varieties of Lycium have
      benn found to be substitutes or adulterants of Lycium barbarum (wolfberry) in
      commercial markets in the Hong Kong Special Administrative Region and in China
      generally. L. barbarum cv. 'Tianjinense' and Lycium chinense var. potaninii are
      the most common examples. It is difficult to differentiate among the Lycium
      species by traditional morphological and histological analyses. An easy and
      reliable approach based on SCAR (sequence characterized amplified region)
      analysis was developed in the present study to differentiate L. barbarum from
      other Lycium species. Two characteristic bands of approx. 700 and 650 bp were
      detected on the RAPD (random amplification of polymorphic DNA) profiles generated
      from samples of L. barbarum and L. chinense var. potaninii using the primer OPC
      7. They were isolated and sequenced. Two primer sets, based on the sequences,
      could amplify a single specific band in samples of L. barbarum respectively,
      whereas no bands were detected in samples of L. chinense var. potaninii. The
      results confirmed that the SCAR technique can be employed for authenticating L.
      barbarum and its adulterants.

PMID- 18052934
TI  - Urocortin 2 combined with angiotensin-converting enzyme inhibition in
      experimental heart failure.
AB  - Ucn2 (urocortin 2) is a recently discovered peptide with therapeutic potential in
      heart failure. As any new treatment is likely to be used in conjunction with
      standard ACEI (angiotensin-converting enzyme inhibitor) therapy, it is important
      that the combined effects of these agents are assessed. In the present study, we
      investigated the effects of Ucn2 and an ACEI (captopril) administered for 3 h,
      both separately and together, in eight sheep with pacing-induced heart failure.
      Ucn2 and captopril alone both increased CO (cardiac output; Ucn2>captopril) and
      decreased arterial pressure (captopril>Ucn2), left atrial pressure
      (Ucn2>captopril) and peripheral resistance (Ucn2=captopril) relative to controls.
      Compared with either treatment alone, combined treatment further improved CO and
      reduced peripheral resistance and cardiac preload, without inducing further falls
      in blood pressure. In contrast with the marked increase in plasma renin activity
      observed with captopril alone, Ucn2 administration reduced renin activity,
      whereas the combined agents resulted in intermediate renin levels. All active
      treatments decreased circulating levels of aldosterone
      (Ucn2+captopril>Ucn2=captopril), endothelin-1 and the natriuretic peptides
      (Ucn2+captopril=Ucn2>captopril), whereas adrenaline (epinephrine) fell only with
      Ucn2 (Ucn2+captopril=Ucn2), and vasopressin increased during captopril alone.
      Ucn2, both separately and in conjunction with captopril, increased urine output,
      sodium and creatinine excretion and creatinine clearance. Conversely, captopril
      administered alone adversely affected these renal indices. In conclusion, co
      treatment with Ucn2 and an ACEI in heart failure produced significantly greater
      improvements in haemodynamics, hormonal profile and renal function than achieved
      by captopril alone. These results indicate that dual treatment with these two
      agents is beneficial.

PMID- 18052935
TI  - Effect of lysosomal storage on bis(monoacylglycero)phosphate.
AB  - BMP [bis(monoacylglycero)phosphate] is an acidic phospholipid and a structural
      isomer of PG (phosphatidylglycerol), consisting of lysophosphatidylglycerol with
      an additional fatty acid esterified to the glycerol head group. It is thought to
      be synthesized from PG in the endosomal/lysosomal compartment and is found
      primarily in multivesicular bodies within the same compartment. In the present
      study, we investigated the effect of lysosomal storage on BMP in cultured
      fibroblasts from patients with eight different LSDs (lysosomal storage disorders)
      and plasma samples from patients with one of 20 LSDs. Using ESI-MS/MS
      (electrospray ionization tandem MS), we were able to demonstrate either
      elevations or alterations in the individual species of BMP, but not of PG, in
      cultured fibroblasts. All affected cell lines, with the exception of Fabry
      disease, showed a loss of polyunsaturated BMP species relative to mono
      unsaturated species, and this correlated with the literature reports of lysosomal
      dysfunction leading to elevations of glycosphingolipids and cholesterol in
      affected cells, processes thought to be critical to the pathogenesis of LSDs.
      Plasma samples from patients with LSDs involving storage in macrophages and/or
      with hepatomegaly showed an elevation in the plasma concentration of the
      C(18:1)/C(18:1) species of BMP when compared with control plasmas, whereas
      disorders involving primarily the central nervous system pathology did not. These
      results suggest that the release of BMP is cell/tissue-specific and that it may
      be useful as a biomarker for a subset of LSDs.

PMID- 18052937
TI  - Bioconversion of small molecules by cytochrome P450 species expressed in
      Escherichia coli.
AB  - P450 (cytochrome P450) enzymes catalyse the mono-oxygenation of a wide range of
      compounds such as steroids, fatty acids, vitamins and drugs. In the present paper
      we demonstrate a system for bioconverting diverse compounds [flavanone, DHEA
      (dehydroepiandrosterone) and 7-ethoxycoumarin] using P450 species expressed in
      Escherichia coli. First, we expressed four P450 species: rabbit CYP2B (P450
      family 2, subfamily B), fruitfly (Drosophila) CYP317A, rat CYP3A23 and mouse
      CYP2J5. Next, we added substrates directly to the incubation medium. The
      resulting metabolites were extracted and analysed by HPLC and spectrofluorimetry.
      The first substrate, 7-ethoxycoumarin, was de-ethylated by CYP2B; CYP2J5 and
      CYP3A23 showed weak activity, and CYP317A had no activity for 7-ethoxycoumarin.
      We next used flavanone, a flavonoid, as a substrate for these four P450 species
      and other P450 species expressed previously. As a result, CYP2B, CYP2C43 and
      CYP2C29 catalysed flavanone 2-hydroxylation. CYP2A5 catalysed 2- and 4
      hydroxylations. Finally, to produce diverse modified compounds, variants of
      CYP2A5 with point mutations were incubated with a steroid (DHEA) and an
      antioxidant (flavanone) in vivo. HPLC analysis indicated that two P450 species
      produced a 7-beta-hydroxy-DHEA and two P450 species produced a 2-alpha-hydroxy
      DHEA. Four P450 species catalysed flavanone 2- and 4-hydroxylations. These
      results indicate that bioconversion by P450 is a useful technique to modify small
      molecules (steroids, coumarin and flavanone) and produce new, diverse
      hydroxylated compounds, which could be used for high-throughput screening for
      drug discovery.

PMID- 18052936
TI  - The guanine-nucleotide-exchange factor BopE from Burkholderia pseudomallei adopts
      a compact version of the Salmonella SopE/SopE2 fold and undergoes a closed-to
      open conformational change upon interaction with Cdc42.
AB  - BopE is a type III secreted protein from Burkholderia pseudomallei, the
      aetiological agent of melioidosis, a severe emerging infection. BopE is a GEF
      (guanine-nucleotide-exchange factor) for the Rho GTPases Cdc42 (cell division
      cycle 42) and Rac1. We have determined the structure of BopE catalytic domain
      (amino acids 78-261) by NMR spectroscopy and it shows that BopE(78-261) comprises
      two three-helix bundles (alpha1alpha4alpha5 and alpha2alpha3alpha6). This fold is
      similar to that adopted by the BopE homologues SopE and SopE2, which are GEFs
      from Salmonella. Whereas the two three-helix bundles of SopE(78-240) and SopE2(69
      240) form the arms of a 'Lambda' shape, BopE(78-261) adopts a more closed
      conformation with substantial interactions between the two three-helix bundles.
      We propose that arginine and proline residues are important in the conformational
      differences between BopE and SopE/E2. Analysis of the molecular interface in the
      SopE(78-240)-Cdc42 complex crystal structure indicates that, in a BopE-Cdc42
      interaction, the closed conformation of BopE(78-261) would engender steric
      clashes with the Cdc42 switch regions. This implies that BopE(78-261) must
      undergo a closed-to-open conformational change in order to catalyse guanine
      nucleotide exchange. In an NMR titration to investigate the BopE(78-261)-Cdc42
      interaction, the appearance of additional peaks per NH for residues in hinge
      regions of BopE(78-261) indicates that BopE(78-261) does undergo a closed-to-open
      conformational change in the presence of Cdc42. The conformational change
      hypothesis is further supported by substantial improvement of BopE(78-261)
      catalytic efficiency through mutations that favour an open conformation.
      Requirement for closed-to-open conformational change explains the 10-40-fold
      lower k(cat) of BopE compared with SopE and SopE2.

PMID- 18052939
TI  - Genes affecting coat colour and pattern in domestic dogs: a review.
AB  - Tremendous progress has been made in identifying genes involved in pigmentation
      in dogs in the past few years. Comparative genomics has both aided and benefited
      from these findings. Seven genes that cause specific coat colours and/or patterns
      in dogs have been identified: melanocortin 1 receptor, tyrosinase related protein
      1, agouti signal peptide, melanophilin, SILV (formerly PMEL17), microphthalmia
      associated transcription factor and beta-defensin 103. Although not all alleles
      have been yet identified at each locus, DNA tests are available for many. The
      identification of these alleles has provided information on interactions in this
      complex set of genes involved in both pigmentation and neurological development.
      The review also discusses pleiotropic effects of some coat colour genes as they
      relate to disease. The alleles found in various breeds have shed light on some
      potential breed development histories and phylogenetic relationships. The
      information is of value to dog breeders who have selected for and against
      specific colours since breed standards and dog showing began in the late 1800s.
      Because coat colour is such a visible trait, this information will also be a
      valuable teaching resource.

PMID- 18052938
TI  - Deprivation of protein or amino acid induces C/EBPbeta synthesis and binding to
      amino acid response elements, but its action is not an absolute requirement for
      enhanced transcription.
AB  - A nutrient stress signalling pathway is triggered in response to protein or amino
      acid deprivation, namely the AAR (amino acid response), and previous studies have
      shown that C/EBPbeta (CCAAT/enhancer-binding protein beta) expression is up
      regulated following activation of the AAR. DNA-binding studies, both in vitro and
      in vivo, have revealed increased C/EBPbeta association with AARE (AAR element)
      sequences in AAR target genes, but its role is still unresolved. The present
      results show that in HepG2 human hepatoma cells, the total amount of C/EBPbeta
      protein, both the activating [LAP* and LAP (liver-enriched activating protein)]
      and inhibitory [LIP (liver-enriched inhibitory)] isoforms, was increased in
      histidine-deprived cells. Immunoblotting of subcellular fractions and
      immunostaining revealed that most of the C/EBPbeta was located in the nucleus.
      Consistent with these observations, amino acid limitation caused an increase in
      C/EBPbeta DNA-binding activity in nuclear extracts and chromatin
      immunoprecipitation revealed an increase in C/EBPbeta binding to the AARE region
      in vivo, but at a time when transcription from the target gene was declining. A
      constant fraction of the basal and increased C/EBPbeta protein was phosphorylated
      on Thr(235) and the phospho-C/EBPbeta did bind to an AARE. Induction of AARE
      enhanced transcription was slightly greater in C/EBPbeta-deficient MEFs (mouse
      embryonic fibroblasts) or C/EBPbeta siRNA (small interfering RNA)-treated HepG2
      cells compared with the corresponding control cells. Transient expression of
      LAP*, LAP or LIP in C/EBPbeta-deficient fibroblasts caused suppression of
      increased transcription from an AARE-driven reporter gene. Collectively, the
      results demonstrate that C/EBPbeta is not required for transcriptional activation
      by the AAR pathway but, when present, acts in concert with ATF3 (activating
      transcription factor 3) to suppress transcription during the latter stages of the
      response.

PMID- 18052940
TI  - QTL detection on porcine chromosome 12 for fatty-acid composition and association
      analyses of the fatty acid synthase, gastric inhibitory polypeptide and acetyl
      coenzyme A carboxylase alpha genes.
AB  - Refinement of previous QTL on porcine chromosome 12 for fatty-acid composition
      and a candidate gene association analysis were conducted using an Iberian x
      Landrace cross. The concentrations of ten fatty acids were assayed in backfat
      tissue from which four metabolic ratios were calculated for 403 F2 animals.
      Linkage analysis identified two significant QTL. The first QTL was associated
      with the average chain length ratio and the percentages of myristic, palmitic and
      gadoleic acids. The second QTL was associated with percentages of palmitoleic,
      stearic and vaccenic acids. Based upon its position on SSC12, fatty acid synthase
      was tested as a candidate gene for the first QTL and no significant effects were
      found. Similarly, gastric inhibitory polypeptide (GIP) and acetyl-coenzyme A
      carboxylase alpha (ACACA) were tested as candidate genes for the second QTL using
      three SNPs in GIP and 15 synonymous SNPs in ACACA cDNA sequences. Two missense
      SNPs in GIP showed significant effects with palmitoleic and stearic fatty-acid
      concentration. Highly significant associations were found for two SNPs in ACACA
      with stearic, palmitoleic and vaccenic fatty-acid concentrations. These
      associations could be due to linkage disequilibrium with the causal mutations.

PMID- 18052941
TI  - Can you shrinkwrap a cow? Protections available for the intellectual property of
      the animal breeding industry.
AB  - There are currently four main intellectual property protection statutory schemes
      available: copyright, trade secret, trademark and patent. Each of these protects
      a different aspect of intellectual property, which leaves gaps of protection when
      an innovation does not fit squarely within the boundaries of the statutes.
      Contracts allow the industry to tailor the protection desired. One very common
      approach is to license the product via contract. Licences allow intellectual
      property owners to retain ownership and give permission to others to use the
      product. Although there are several types of licences, the most common is the
      field of use licence, which limits the licensee's use of the product. This often
      leads to price discrimination where various levels of restriction are offered at
      corresponding prices. The more rights retained by the owner, the more restricted
      the buyer is and the lower the purchase price allowing customers to choose the
      level of restriction they are willing to accept. Therefore, the different uses
      and needs of various customers can be accounted for and reflected in the price.
      The animal breeding industry is currently struggling to protect their innovations
      falling into these statutory gaps. The protection for animal breeding industry
      innovations is most likely through contract law rather than traditional
      intellectual property law. By taking advantage of the unique nature of contracts,
      industry will be able to tailor protection and pricing to best suit the variety
      of customers and uses for the products sold.

PMID- 18052942
TI  - Intraindividual variation in levels of serum testosterone and other reproductive
      and adrenal hormones in men.
AB  - BACKGROUND: Estimates of intraindividual variation in hormone levels provide the
      basis for interpreting hormone measurements clinically and for developing
      eligibility criteria for trials of hormone replacement therapy. However, reliable
      systematic estimates of such variation are lacking. OBJECTIVE: To estimate
      intraindividual variation of serum total, free and bioavailable testosterone (T),
      dihydrotestosterone (DHT), SHBG, LH, dehydroepiandrosterone (DHEA),
      dehydroepiandrosterone sulphate (DHEAS), oestrone, oestradiol and cortisol, and
      the contributions of biological and assay variation to the total. DESIGN: Paired
      blood samples were obtained 1-3 days apart at entry and again 3 months and 6
      months later (maximum six samples per subject). Each sample consisted of a pool
      of equal aliquots of two blood draws 20 min apart. STUDY PARTICIPANTS: Men aged
      30-79 years were randomly selected from the respondents to the Boston Area
      Community Health Survey, a study of the health of the general population of
      Boston, MA, USA. Analysis was based on 132 men, including 121 who completed all
      six visits, 8 who completed the first two visits and 3 who completed the first
      four visits. MEASUREMENTS: Day-to-day and 3-month (long-term) intraindividual
      standard deviations, after transforming measurements to logarithms to eliminate
      the contribution of hormone level to intraindividual variation. RESULTS:
      Biological variation generally accounted for more of total intraindividual
      variation than did assay variation. Day-to-day biological variation accounted for
      more of the total than did long-term biological variation. Short-term variability
      was greater in hormones with pulsatile secretion (e.g. LH) than those that
      exhibit less ultradian variation. Depending on the hormone, the intraindividual
      standard deviations imply that a clinician can expect to see a difference
      exceeding 18-28% about half the time when two measurements are made on a subject.
      The difference will exceed 27-54% about a quarter of the time. CONCLUSIONS: Given
      the level of intraindividual variability in hormone levels found in this study,
      one sample is generally not sufficient to characterize an individual's hormone
      levels but collecting more than three is probably not warranted. This is true for
      clinical measurements and for hormone measurements used to determine eligibility
      for a clinical trial of hormone replacement therapy.

PMID- 18052943
TI  - Factors associated with elevated serum concentrations of anti-TPO antibodies in
      subjects with and without diffuse goitre. Results from the Ukrainian-American
      Cohort Study of thyroid cancer and other thyroid diseases following the Chornobyl
      accident.
AB  - OBJECTIVES: To examine factors associated with the prevalence of elevated anti
      thyroid peroxidase antibodies (ATPO) among iodine-deficient adolescents and young
      adults and test whether associations vary according to the presence of diffuse
      goitre. DESIGN: Subjects were members of the Ukrainian-American Cohort Study
      exposed to the Chornobyl accident whose (131)I thyroid dose estimates were below
      0.2 Gy. MEASUREMENTS: The odds ratios (ORs) for ATPO above 60 U/ml were estimated
      using logistic regression models for a number of factors in the total population
      (N = 5133), and separately for thyroid disease-free subjects (N = 3875), those
      with diffuse goitre (N = 921), and diffuse goitre without autoimmune thyroiditis
      (AIT; N = 883). RESULTS: Elevated ATPO was found in 9.9% of the total population
      and ORs were significantly higher in females, older individuals, those examined
      in earlier calendar years, residents of Kyiv and Chernihiv oblasts, subjects with
      a family history of thyroid disease, higher thyroid ultrasound volume, suppressed
      or elevated TSH, blood collection in March to May, very low thyroglobulin (Tg),
      and shorter serum storage time. When thyroid disease-free subjects and those with
      diffuse goitre were compared, there were few differences in antibody prevalence,
      and after excluding individuals with AIT, the only difference was an increased
      prevalence of elevated ATPO at low urinary iodine in those with goitre alone.
      CONCLUSIONS: Although a number of factors are associated with the prevalence of
      elevated ATPO in our study group, with the exception of urinary iodine these
      factors are independent of goitre, and differences between thyroid disease-free
      subjects and those with diffuse goitre are largely due to AIT.

PMID- 18052944
TI  - Active migration into the subcellular space precedes Campylobacter jejuni
      invasion of epithelial cells.
AB  - The bacterial pathogen Campylobacter jejuni invades mucosal cells via largely
      undefined and rather inefficient (0.01-2 bacteria per cell) mechanisms. Here we
      report a novel, highly efficient C. jejuni infection pathway resulting in 10-15
      intracellular bacteria per cell within 3 h of infection. Electron microscopy,
      pulse-chase infection assays and time-lapse multiphoton laser confocal microscopy
      demonstrated that the mechanism involved active and rapid migration of the
      pathogen into the subcellular space (termed 'subvasion'), followed by bacterial
      entry ('invasion') at the cell basis. Efficient subvasion was maximal after
      repeated rounds of selection for the subvasive phenotype. Targeted mutagenesis
      indicated that the CadF, JlpA or PEB1 adhesins were not required. Dissection of
      the selected and parental phenotypes by SDS-PAGE yielded comparable capsule
      polysaccharide and lipooligosaccharide profiles. Proteomics revealed reduced
      amounts of the chemotaxis protein CheW for the subvasive phenotype. Swarming
      assays confirmed that the selected phenotype exhibited altered migration
      behaviour. Introduction of a plasmid carrying chemotaxis genes into the subvasive
      strain yielded wild-type subvasion levels and migration behaviour. These results
      indicate that alterations in the bacterial migration machinery enable C. jejuni
      to actively penetrate the subcellular space and gain access to the cell interior
      with unprecedented efficiency.

PMID- 18052945
TI  - Conversion of apical plasma membrane sphingomyelin to ceramide attenuates the
      intoxication of host cells by cholera toxin.
AB  - Cholera toxin (CT) enters host cells by binding to ganglioside GM1 in the apical
      plasma membrane (PM). GM1 carries CT retrograde from the PM to the endoplasmic
      reticulum (ER), where a portion of the toxin, the A1-chain, retro-translocates to
      the cytosol, causing disease. Trafficking in this pathway appears to depend on
      the association of CT-GM1 complexes with sphingomyelin (SM)- and cholesterol-rich
      membrane microdomains termed lipid rafts. Here, we find that in polarized
      intestinal epithelia, the conversion of apical membrane SM to ceramide by
      bacterial sphingomyelinase attenuates CT toxicity, consistent with the lipid raft
      hypothesis. The effect is reversible, specific to toxin entry via the apical
      membrane, and recapitulated by the addition of exogenous long-chain ceramides.
      Conversion of apical membrane SM to ceramide inhibits the efficiency of toxin
      endocytosis, but retrograde trafficking from the apical PM to the Golgi and ER is
      not affected. This result suggests that the cause for toxin resistance occurs at
      steps required for retro-translocation of the CT A1-chain to the cytosol.

PMID- 18052947
TI  - Migraine and the risk of stroke, TIA, or death in the UK (CME).
AB  - BACKGROUND: Previous observational studies have reported a higher risk of stroke
      in migraine patients. Objective.- We aimed to estimate the risk of stroke,
      transient ischemic attack (TIA), or death in migraineurs in the UK. METHOD: We
      conducted a population-based follow-up study within the General Practice Research
      Database from 1994 to 2001. RESULTS: The relative risk (RR) of stroke in
      migraineurs compared with non-migraineurs was 2.2 (95% confidence interval [CI]
      1.7-2.9). It was highest for patients with a migraine diagnosis recorded within
      30 days prior to a stroke (odds ratio 11.1, 95% CI 5.69-21.5). The RR of TIA in
      migraineurs compared with non-migraineurs was 2.4 (95% CI 1.8-3.3), the mortality
      of migraineurs was slightly decreased. CONCLUSION: In our study, the RR of
      developing a stroke or a TIA was doubled in migraineurs as compared with non
      migraineurs, while that for death was close to unity.

PMID- 18052948
TI  - Effect of carbon dioxide on calcitonin gene-related peptide secretion from
      trigeminal neurons.
AB  - OBJECTIVE: The goal of this study was to determine whether the physiological
      effects of carbon dioxide (CO(2)) involve regulation of CGRP secretion from
      trigeminal sensory neurons. BACKGROUND: The neuropeptide calcitonin gene-related
      peptide (CGRP) is implicated in the pathophysiology of allergic rhinosinusitis
      and migraine. Recent clinical evidence supports the use of noninhaled intranasal
      delivery of 100% CO(2) for treatment of these diseases. Patients report 2
      distinct physiological events: first, a short duration stinging or burning
      sensation within the nasal mucosa, and second, alleviation of primary symptoms.
      METHODS: Primary cultures of rat trigeminal ganglia were utilized to investigate
      the effects of CO(2) on CGRP release stimulated by a depolarizing stimulus (KCl),
      capsaicin, nitric oxide, and/or protons. The amount of CGRP secreted into the
      culture media was determined using a CGRP-specific radioimmunoassay.
      Intracellular pH and calcium levels were measured in cultured trigeminal neurons
      in response to CO(2) and stimulatory agents using fluorescent imaging techniques.
      RESULTS: Incubation of primary trigeminal ganglia cultures at pH 6.0 or 5.5 was
      shown to significantly stimulate CGRP release. Similarly, CO(2) treatment of
      cultures caused a time-dependent acidification of the media, achieving pH values
      of 5.5-6 that stimulated CGRP secretion. In addition, KCl, capsaicin, and a
      nitric oxide donor also caused a significant increase in CGRP release.
      Interestingly, CO(2) treatment of cultures under isohydric conditions, which
      prevents extracellular acidification while allowing changes in PCO(2) values,
      significantly repressed the stimulatory effects of KCl, capsaicin, and nitric
      oxide on CGRP secretion. We found that CO(2) treatment under isohydric conditions
      resulted in a decrease in intracellular pH and inhibition of the KCl- and
      capsaicin-mediated increases in intracellular calcium. CONCLUSIONS: Results from
      this study provide the first evidence of a unique regulatory mechanism by which
      CO(2) inhibits sensory nerve activation, and subsequent neuropeptide release.
      Furthermore, the observed inhibitory effect of CO(2) on CGRP secretion likely
      involves modulation of calcium channel activity and changes in intracellular pH.

PMID- 18052949
TI  - The impact of topiramate on health-related quality of life indicators in chronic
      migraine.
AB  - BACKGROUND: Chronic migraine is a disabling primary chronic daily headache
      disorder that significantly impacts the daily activities of patients with this
      disorder. To our knowledge, this is the first report of a large, randomized,
      double-blind, placebo-controlled trial that assessed the impact of topiramate on
      the daily activities, emotional distress, headache-related disability, and global
      impression of change in patients with chronic migraine. OBJECTIVE: To assess
      whether topiramate 100 mg/day reduces migraine-related disability and limitations
      of daily activities in patients with chronic migraine. STUDY DESIGN/METHODS:
      Patients aged > or =18 years with chronic migraine were randomized 1 : 1 ratio to
      topiramate 100 mg/day or placebo. The double-blind period lasted 16 weeks. Three
      patient-reported outcome measures were administered: Migraine Disability
      Assessment, Migraine-Specific Quality of Life Questionnaire (Domains: Role
      Function Restrictive and Preventive and Emotional Function), and Subject's Global
      Impression of Change. Investigators completed a Physician's Global Impression of
      Change for each patient. Subject's Global Impression of Change and Physician's
      Global Impression of Change were completed one time, at the end of study, and
      measured on a 7-point scale (1 = very much improved to 7 = very much worse). The
      Migraine-Specific Quality of Life Questionnaire was analyzed using analysis of
      covariance (last observation carried forward) approach. Results were not adjusted
      for multiplicity. RESULTS: A total of 328 patients were randomized (topiramate, n
      = 165; placebo, n = 163), and 306 patients were included in the intent-to-treat
      population. Mean age was 38.2 years, and a majority of the patients were female
      (85.3%). Fifty-six percent of topiramate-treated patients vs 45% of placebo
      treated patients reported >50% improvement from baseline in Migraine Disability
      Assessment scores (P = .074). The Migraine-Specific Quality of Life Questionnaire
      analysis demonstrated significant improvements at week 4 in all 3 domains, and at
      weeks 8 and 16 in both Role Function-Restrictive and Emotional Function domains
      (P < .05). Role Function-Preventive approached, but did not reach significance,
      at week 8 (P = .053). Seventy-five percent and 72% of topiramate-treated patients
      vs 61% and 59% of placebo-treated patients reported improvements on the Subject
      and Physician's Global Impression of Change scales (P = .025 and P = .037,
      respectively). CONCLUSION: Compared with placebo-treated patients, topiramate 100
      mg/day appears to contribute to reductions in migraine-related limitations on
      daily activities and emotional distress beginning as early as week 4 and
      continuing up to week 16 after treatment. Physician's Global Impression of Change
      results are very similar with Subject's Global Impression of Change, indicating
      concordance between the physician's and the subject's assessment of improvement.

PMID- 18052950
TI  - A double-blind, dose comparison study of topiramate for prophylaxis of basilar
      type migraine in children: a pilot study.
AB  - BACKGROUND: Basilar-type migraine (BM) is the most common migraine "variant,"
      representing 3-19% of migraine in children.BMis characterized by attacks of
      dizziness, vertigo, visual disturbances, ataxia, and/or diplopia, followed by
      migraine headache. OBJECTIVE: The objective of this study is to assess the
      efficacy and safety of topiramate for prophylaxis of BM in children and
      adolescents (6-18 years). DESIGN: Outpatient, double-blind, parallel-group, dose
      comparison study with 2 phases: prerandomization (screening/washout and 4-week
      prospective baseline) and 12-week double blind (titration and maintenance).
      METHODS: Following consent and assent, subjects with BMs, as defined by the
      International Classification of Headache Disorders (second edition), and > or =4
      migraines/month were randomized to receive either 25 mg per day or 100 mg per day
      of topiramate in a 1 : 1 ratio. RESULTS: Fourteen children (4 boys, 10 girls)
      completed the double-blind phase (7 in the 25-mg group and 7 in the 100-mg
      group). During the prospective baseline, the mean headache frequency of the
      combined group "all migraines" per month was 4.5/month (25 mg) and 4.8/month (100
      mg). Average duration of migraine was 5.5 hours (25 mg) and 5.0 hours (100 mg)
      and average mean pain (5-point faces scale) was 3.3 for both (25 mg 100 mg). The
      reduction in median monthly migraine rate during the double-blind treatment phase
      relative to baseline was 2.9 (64.4%) and 3.6 (75.0%) for the 25-mg and 100-mg
      topiramate-treated groups, respectively (P < .001). The reduction in median
      monthly BM rate during the double-blind treatment phase relative to baseline was
      2.5 (74.24%) and 2.3 (82.8%) for the 25-mg and 100-mg topiramate-treated groups,
      respectively. The overall reduction in BM attacks reduced from 2.84/month to
      0.59/month (79.2%; P < .0042). Overall, 86% of patients responded with a greater
      than 50% reduction in migraine frequency (100%, 25 mg and 71%, 100 mg). Mean
      reduction in migraine duration was 18 minutes (25 mg) and 89 minutes (100 mg).
      There was no significant difference in migraine severity between the 2 groups.
      Parent Global Assessment was "very much" or "much improved" in 6 of 7 (25 mg) and
      3 of 7 (100 mg) patients. Migraine disability as measured by PedMidas reduced
      from moderate to no disability (P < .001). There were no serious adverse events.
      CONCLUSIONS: Preventive therapy with topiramate resulted in reducing the overall
      migraine frequency and the frequency of attacks of BM at both 25 mg and 100 mg
      doses relative to the historical baseline and prospective baseline periods. The 2
      treatment groups resulted in comparable outcomes.

PMID- 18052951
TI  - Hypothalamic activation in spontaneous migraine attacks.
AB  - BACKGROUND: Migraine sufferers experience premonitory symptoms which suggest that
      primary hypothalamic dysfunction is a likely trigger of the attacks.
      Neuroendocrine and laboratory data also support this hypothesis. To date,
      positron emission tomography (PET) scans of migraine sufferers have demonstrated
      activation of brainstem nuclei, but not of the hypothalamus. OBJECTIVE: To record
      cerebral activations withH2 15OPET during spontaneous migraine without aura
      attacks. METHODS: We scanned 7 patients with migraine without aura (6 females and
      1 male) in each of 3 situations: within 4 hours of headache onset, after headache
      relief by sumatriptan injection (between the fourth and the sixth hour after
      headache onset), and during an attack-free period. RESULTS: During the headache
      we found not only significant activations in the midbrain and pons, but also in
      the hypothalamus, all persisting after headache relief by sumatriptan.
      CONCLUSION: Hypothalamic activity, long suspected by clinical and experimental
      arguments as a possible trigger for migraine, is demonstrated for the first time
      during spontaneous attacks.

PMID- 18052952
TI  - Prevalence of vertigo, dizziness, and migrainous vertigo in patients with
      migraine.
AB  - OBJECTIVE: The aim of this study was to determine the lifetime prevalence of
      vertigo and dizziness in patients with migraine as compared with controls and to
      establish the lifetime prevalence of migrainous vertigo. BACKGROUND: Dizziness
      and vertigo are relatively frequent complaints in general population; however,
      the prevalence of migrainous vertigo has not been extensively studied so far.
      METHODS: The study included 327 migraine patients and 324 controls who do not
      suffer from frequent headaches. The study and control group were assessed
      clinically and through diagnostic workup for having vertigo, dizziness,
      hypotension, and sideropenic anemia. RESULTS: Vertigo or dizziness was
      experienced by 51.7% of migraine patients (MVL group) and 31.5% in the control
      group (CVL group), P < .0001. Among the MVL group, 23.2% of patients met the
      criteria for migrainous vertigo. There was no difference between the MVL group
      and CVL group in frequency of attacks or the pattern of symptom appearance in
      relation to head movement. Patients in the MVL group more frequently had
      hypotension, P = .011. Patients with migraine with aura significantly more often
      had migraine attacks in association with vertigo or dizziness, P < .0001.
      CONCLUSION: The lifetime prevalence of migrainous vertigo is relatively frequent
      in migraine patients, especially in migraine with aura.

PMID- 18052953
TI  - Insulin metabolism is altered in migraineurs: a new pathogenic mechanism for
      migraine?
AB  - BACKGROUND: Migraine is a complex biochemical dysfunction attributed to a
      disorder of the trigeminal and hypothalamic pathways. Impairment of glucose
      metabolism has been reported in migraine, but data are scanty and inconsistent.
      OBJECTIVE: The main aim was to verify whether migraineurs have abnormalities of
      the glucose and insulin metabolism. We also studied correlations between blood
      glucose and insulin and between insulin levels and migraine severity. PATIENTS
      AND METHODS: Patients with migraine or headache other than migraine, and healthy
      volunteers were included. All had general blood tests and a standard oral glucose
      tolerance test after a 12-hour fast, and glucose and insulin were measured.
      RESULTS: Over a 6-month period, we recruited 84 migraineurs (73 women, 11 men),
      25 patients with nonmigraine headache (20 women, 5 men), and 26 healthy controls
      (24 women, 2 men). Multivariate analysis confirmed a significant difference
      between groups for glucose levels (P < .0001), but no significant time
      interaction. The differences were mostly between migraine and healthy controls (P
      < .0001) and to a lesser extent between other headaches and healthy controls (P <
      .05). A significant difference between groups was also found for insulin (P <
      .0001), with a significant time interaction. The difference was confirmed for
      migraine compared to other headaches (P < .0001) and healthy controls (P <
      .0001). CONCLUSIONS: Blood glucose levels may be high in headache patients, but
      do not seem to be specific to migraineurs. Insulin levels were higher in
      migraineurs, and seemed specific to this group. These findings are in keeping
      with recent reports on the effects of insulin on brain functions and lend support
      to the possibility that insulin is involved in the pathogenesis of migraine.

PMID- 18052954
TI  - Images from headache: external hydrocephalus due to cryptococcal meningitis.

PMID- 18052955
TI  - Bilateral carotid artery dissection after dental work.
AB  - Carotid artery dissection has been reported to occur spontaneously and after many
      types of neck trauma. A case patient is presented who developed a right-sided
      oculosympathetic palsy and was found to have bilateral carotid artery dissection
      after she visited her dentist. To the best of our knowledge, this case represents
      the first report of bilateral carotid dissection following dental work.

PMID- 18052956
TI  - Giant cell arteritis with multiple cranial nerve palsy and reversible proptosis:
      a case report.
AB  - Giant cell arteritis (GCA) often presents with symptoms of headache, jaw
      claudication, polymyalgia rheumatica, and blurred vision. GCA is relatively rare
      and may have atypical manifestations in Asians, including multiple cranial nerve
      palsy and reversible proptosis. A high suspicion of GCA is suggested when any
      older Asian suffers from headache that is new-onset or different from the
      previous pattern, even without other typical manifestations of GCA.

PMID- 18052957
TI  - Diffusion MRI during migraine with aura attack associated with diagnostic
      microbubbles injection in subjects with large PFO.
AB  - The relationship between migraine with aura and patent foramen ovale (PFO) is
      still debatable. We report 2 cases of migraine with aura attacks after diagnostic
      microbubble injection for contrast transcranial Doppler (cTCD), in subjects with
      large PFO. In one case MR images, including diffusion weighted imaging and
      apparent diffusion coefficient, performed during aura did not show any signal
      abnormality. Patients with migraine with aura may have an attack during cTCD,
      probably by a "non-ischemic" mechanism.

PMID- 18052959
TI  - Migraine pain--intracranial or extracranial?

PMID- 18052958
TI  - Aquaporin 1 may be involved in the pathophysiology of migraine: a hypothesis.

PMID- 18052960
TI  - PRO-513 for acute migraine treatment.

PMID- 18052961
TI  - Teaching case: intractable posterior headache.

PMID- 18052963
TI  - IL-21 modulates CD4+ CD25+ regulatory T-cell homeostasis in experimental
      autoimmune encephalomyelitis.
AB  - The homeostasis of CD4+ CD25+ regulatory T cells (Tregs) depends on the cytokine
      interleukin (IL)-2. As IL-21 shares sequence homology with IL-2 and the IL-21
      receptors contain a gamma-chain common to IL-2, we hypothesized that IL-21 could
      also affect the homeostasis of Tregs. We tested this hypothesis in experimental
      autoimmune encephalomyelitis (EAE), an animal model of relapsing-remitting human
      multiple sclerosis. We show that blockade of IL-21 in SJL/J mice before and after
      the induction of EAE enhances the influx of inflammatory cells into the central
      nervous system (CNS). The blockade of IL-21 leads to proliferation of proteolipid
      peptide (PLP(139-151))-autoreactive CD4+ T cells, which are capable to cause
      severe EAE in adoptively transferred recipient mice. Conversely, Tregs from mice
      where IL-21 was blocked, lose their capacity to prevent EAE induced PLP(139-151)
      reactive T cells. Notably, direct effects of IL-21 on Tregs are confirmed by
      studies of blockade of IL-21 in mice expressing a green fluorescent protein
      'knocked' into a Foxp3 allele, in which a reduction of the number of Tregs and a
      downregulation of their frequency and expression of Foxp3 are observed. These
      data suggest a role of the IL-21/IL-21R axis in the homeostasis of Tregs in CNS
      autoimmunity.

PMID- 18052964
TI  - Effects of single administration of morphine on G-protein mRNA level in the
      presence and absence of inflammation in the rat spinal cord.
AB  - Antinociceptive potency of opioids is greater against various noxious stimuli in
      animals with peripheral inflammation. Opioid agonists stimulate activation of G
      protein-coupled receptor. Changes in the resting levels of G-protein subtypes
      could have an effect on intracellular signalling pathways. The present study was
      designed to investigate the effects of analgesic morphine treatment on the level
      G-protein subunits mRNA in the presence and absence of inflammation. Our results
      showed that the carrageenan administration increased G-protein subunits.
      Administration of analgesic dose of morphine alone and in the presence of
      inflammation induced different alterations in the levels of G-protein mRNA. Taken
      together, the results obtained using real time RT-PCR suggested that G-protein
      genes expression levels following the acute administration of morphine between
      animals with and without inflammation could influence, at least in part,
      analgesic responsiveness.

PMID- 18052965
TI  - Expression of human TIM-1 and TIM-3 on lymphocytes from systemic lupus
      erythematosus patients.
AB  - The T-cell immunoglobulin- and mucin-domain-containing molecules (TIMs) comprise
      a new family of cell surface molecules expressed on T cells. TIM-3 is expressed
      on T helper type 1 (Th1) cells and implicated in the pathogenesis of Th1-driven
      auto- and allo-immune diseases. TIM-1 is suggested to act as a co-stimulatory
      molecule for all T cells, but with potentially stronger effects on Th2 than Th1
      cells and is associated with Th2-related immune diseases. However, the TIM
      molecules have not been investigated in the systemic lupus erythematosus (SLE).
      In this study, we examined the expression of TIM-1 and TIM-3 on peripheral blood
      mononuclear cells from SLE patients using quantitative real-time RT-PCR. An
      increased TIM-1 expression was detected in SLE patients, which correlates with
      interleukin-10 expression. We also found that there was a significant increase in
      the expression of TIM-1 in SLE patients with quite active disease (SLE disease
      activity index > 6), indicating that TIM-1 expression might be related to active
      clinical phases. In contrast, TIM-3 expression remained normal in SLE patients
      with low statistical power (34.89%). However, the expression of TIM-3 ligand,
      galectin-9 increased in SLE patients indicating an enhanced engagement of TIM-3
      with its ligand in SLE, which may result in a decreased regulatory T-cell
      function as shown by the decreased expression of FoxP3 and TGF-beta1 in SLE.
      These data suggest that TIM-1 and TIM-3/TIM-3L are involved in the pathogenesis
      of SLE.

PMID- 18052966
TI  - Circulating surfactant protein D is decreased in early rheumatoid arthritis: a 1
      year prospective study.
AB  - Innate immune system abnormalities, e.g., mannan-binding lectin (MBL) genotype
      variants, have been demonstrated to modify the disease course of rheumatoid
      arthritis (RA). Surfactant protein D (SP-D) shares important structural and
      functional properties with MBL suggesting that SP-D may be an additional RA
      disease modifier. The Met11Thr polymorphism in the N-terminal part of SP-D is an
      important determinant for the SP-D serum level, but this polymorphism is also
      essential to the function and assembly into oligomers. We aimed to compare the
      serum levels of SP-D in a cohort of newly diagnosed untreated RA patients with
      healthy matched controls, and to investigate if there was an association to core
      measures of disease activity within the first year after disease onset. Secondly,
      we aimed to investigate whether the Met11Thr polymorphism was associated with RA.
      Serum SP-D was significantly lower in DMARD naive RA patients compared with
      healthy controls (P = 0.016). Median SP-D concentration at inclusion was 878
      ng/ml (95% CI: 730-1033) and 1164 ng/ml (95% CI: 1093-1366) in RA patients and
      matched controls, respectively. SP-D increased during Methotrexate treatment (P <
      0.0001), and at 1-year follow-up median SP-D was 1032 ng/ml (95% CI: 777-1255).
      SP-D levels did not correlate with traditional disease activity measures. The
      Thr11/Thr11 genotype and the Thr11 allele tended to be more frequent in RA
      patients. In conclusion, the low serum level of SP-D and the lack of correlation
      with traditional disease activity measures indicate that SP-D reflects a
      distinctive aspect in the RA pathogenesis.

PMID- 18052967
TI  - Expression and regulation of the CC-chemokine ligand 20 during human
      tuberculosis.
AB  - CC-chemokine ligand 20 (CCL20), a unique chemokine ligand of CC-chemokine
      receptor 6 (CCR6), play roles in various pathologic conditions. However, the
      characteristic expression profiles of CCL20 during human tuberculosis (TB) have
      been largely unknown. The present study analyzed the production and regulatory
      mechanisms of CCL20 in peripheral blood mononuclear cells (PBMC) and monocyte
      derived macrophages (MDM) from active pulmonary TB patients and healthy controls
      (HC). The 30-kDa antigen (Ag) of Mycobacterium tuberculosis actively induced the
      production of CCL20 by human PBMC and MDM. A comparative analysis revealed that
      the expression of CCL20 protein was prominently up-regulated in PBMC, MDM,
      bronchoalveolar lavage fluids (not in sera) from TB patients compared with the
      corresponding cells or body fluids from HC. Blockade of either tumour necrosis
      factor-alpha or interferon-gamma, but not interleukin-10, significantly
      attenuated the CCL20 production. In addition, recombinant CCL20 induced CCR6
      expression by CD45RO+ T lymphocytes in a dose-dependent manner. Furthermore, the
      expression of CCR6 was significantly increased in CD45RO+ T lymphocytes from TB
      patients, as compared with those from HC. Pharmacological inhibition studies
      showed that the 30-kDa Ag-induced CCL20 mRNA expression involves mitogen
      activated protein kinases (MAPK; extracellular signal-regulated kinase 1/2 and
      p38)- and NF-kappaB-dependent signalling. Collectively, the present study
      demonstrated that TB patients show the up-regulated expression of CCL20, which is
      modulated by proinflammatory cytokines, and through MAPK/NF-kappaB-mediated
      transcriptional mechanisms. The findings suggest important implications of
      potential roles of CCL20-CCR6 in immunopathogenesis of TB.

PMID- 18052968
TI  - Enumeration of haemagglutinin-specific CD8+ T cells after influenza vaccination
      using MHC class I peptide tetramers.
AB  - With emergence of MHC class I tetramers loaded with CD8+ T-cell viral epitopes,
      it is possible to study virus-specific CD8 cells in humans during infection and
      after vaccination. MHC class I tetramers was used to detect the frequency of
      haemagglutinin (HA)-specific T cells in 26 healthy influenza-vaccinated humans.
      Peripheral blood was collected before, and 7, 14 and 28 days after vaccination.
      Four-colour flow cytometry was used for monitoring of vaccine induced T-cell
      response. In 15 donors, two- to fivefold increase in frequency of HA-specific T
      cells was observed 7 days after vaccination. In addition, in 12 of these donors,
      this increase was accompanied with fourfold increase of H1N1 antibody titre. The
      increase in frequency of HA-specific CD8+/IFN-gamma+ cells was low and peaked 28
      days after vaccination in three of the six donors tested. Frequencies of HA
      specific CD8+ T cells and antibody titre returned to prevaccination values 1 year
      after vaccination. Subunit influenza vaccines have the ability to induce HA
      specific CD8+ cells. As the immune response to this vaccine decreased
      significantly after 1 year, our results confirm the importance of annual
      immunization for adequate protection.

PMID- 18052969
TI  - Differences in intermale aggression are accompanied by opposite vasopressin
      release patterns within the septum in rats bred for low and high anxiety.
AB  - Several studies suggest a role for arginine vasopressin (AVP), particularly in
      the lateral septum, in the regulation of intermale aggression. We used
      intracerebral microdialysis to monitor the local in vivo AVP release within the
      mediolateral septum of adult male Wistar rats bred for low (LAB) or high (HAB)
      anxiety-related behaviour during exposure to the resident-intruder test. LAB
      residents showed a significantly higher level of aggression than HAB residents,
      as reflected by more time spent with lateral threat, offensive upright and total
      aggressive behaviour as well as by more attacks and a shorter attack latency.
      Septal AVP release was significantly decreased in high-aggressive LAB males,
      while septal AVP release tended to increase in HAB males during resident-intruder
      test exposure. Moreover, LAB residents showed reduced neuronal activation of the
      lateral septum, as indicated by fewer c-Fos-positive cells, 1 h after the
      resident-intruder test. Pharmacological manipulation of the septal AVP system by
      local application of either synthetic AVP to LAB residents or the selective V1a
      receptor antagonist d(CH(2))(5)Tyr(Me)AVP to HAB residents did not change the
      level of aggression. However, application of AVP into the septum enhanced anxiety
      related behaviour on the elevated plus-maze in LAB males, while local
      administration of the V1a receptor antagonist reduced social investigation in HAB
      males during the resident-intruder test. In conclusion, although AVP release
      patterns within the septum are dependent on the level of aggression, locally
      released AVP does not seem to be directly involved in the regulation of
      aggression, but rather modulates non-aggressive social and anxiety-related
      behaviours.

PMID- 18052970
TI  - Brief treatment with the glucocorticoid receptor antagonist mifepristone
      normalizes the reduction in neurogenesis after chronic stress.
AB  - In rodents, stress suppresses adult neurogenesis. This is thought to involve
      activation of glucocorticoid receptors in the brain. In the present study, we
      therefore questioned whether glucocorticoid receptor blockade by mifepristone can
      normalize the effects of chronic stress on adult neurogenesis. Rats received
      mifepristone on the last 4 days of a 21-day chronic unpredictable and inescapable
      stress regimen. Neurogenesis was analysed by stereological quantification of
      adult-generated cell survival (bromodeoxyuridine), young neuronal survival
      (doublecortin) and cell proliferation (Ki-67). The results show that only 4 days
      of mifepristone treatment normalized the stress-induced reductions in
      neurogenesis. Importantly, mifepristone by itself had no effect on neurogenesis.
      We conclude that, contrary to other compounds interfering with the effects of
      chronic stress on neurogenesis, like antidepressants, the normalizing effects of
      mifepristone on neurogenesis are rapid and particularly potent in a high stress
      environment. This neurogenic action of mifepristone could potentially contribute
      to its clinical mechanism of action.

PMID- 18052971
TI  - Complement activation contributes to leukocyte recruitment and neuropathic pain
      following peripheral nerve injury in rats.
AB  - Complement activation triggers inflammation and has been implicated in
      neurological diseases associated with pain. However, the role of complement in
      neuropathic pain has not been clearly defined. In this study, we tested whether
      complement is activated by partial ligation of the rat sciatic nerve, a widely
      used model of neuropathic pain, and whether complement activation or inhibition
      in peripheral nerve influences leukocyte recruitment and neuropathic pain. We
      found that C3 deposition significantly increased from 6 h to 7 days in the
      injured nerve and was associated with the extent of thermal hyperalgesia and
      mechanical allodynia. However, no deposition of the membrane attack complex was
      detected. Complement activation by endoneurial injection of aggregated rat
      immunoglobulin G into normal sciatic nerve produced significant thermal
      hyperalgesia and mechanical allodynia of the ipsilateral hindpaw at 2-7 days
      after injection. This was accompanied by increased deposition of C3 and
      recruitment of macrophages at 7 days following injection. Complement inhibition
      using systemic injections of soluble complement receptor 1 (AVANT
      Immunotherapeutics, Inc., Needham, USA) into rats markedly suppressed C3
      deposition and T-cell and macrophage recruitment to the injured nerve, and
      produced significant alleviation of thermal hyperalgesia and mechanical
      allodynia. These results demonstrate that C3 activation in the nerve contributes
      to increased infiltration of inflammatory cells and to neuropathic pain behaviors
      following peripheral nerve injury. Complement inhibition may be a potential
      therapeutic treatment for neuropathic pain.

PMID- 18052972
TI  - Two types of social buffering differentially mitigate conditioned fear responses.
AB  - In a phenomenon known as 'social buffering' in various species, signals from a
      conspecific animal can mitigate stress responses. This buffering can be achieved
      either by 'pair-housing' after a stressful event or by 'pair-exposure' to an
      acute stressor with a conspecific animal. In this study, we compared the impacts
      of these two types of social buffering on auditory conditioned fear responses in
      male rats. When subjects were exposed to an auditory conditioned stimulus (CS)
      that had been paired with foot shocks on the previous day, they clearly exhibited
      behavioral (freezing), autonomic (aggravated stress-induced hyperthermia) and
      neural (Fos expression) responses. Pair-housing for 24 h with an unfamiliar rat
      following fear conditioning resulted in a suppressed autonomic, but not
      behavioral, response, with Fos expression in the lateral nucleus of the amygdala
      and ventrolateral periaqueductal gray. On the other hand, pair-exposure to the CS
      with an unfamiliar rat eliminated the behavioral, but not the autonomic,
      response, with Fos expression in the basal nucleus of the amygdala and
      infralimbic region of the prefrontal cortex. Furthermore, subjects that had been
      pair-housed and then pair-exposed showed no behavioral, autonomic or neural
      responses, suggesting that the combination of the two procedures can completely
      block the fear conditioning sequence. These results demonstrate that two types of
      social buffering differentially relieve conditioned fear responses, by
      influencing different neural pathways in the amygdala.

PMID- 18052973
TI  - Up-regulation of adenosine A1 receptors in frontal cortex from Pick's disease
      cases.
AB  - The adenosine A(1) receptor (A(1)R)-adenylyl cyclase (AC) pathway was studied in
      post-mortem human frontal and occipital cortex from Pick's disease (PiD) cases
      and age-matched nondemented controls. In frontal cortex, the main brain area
      affected in PiD, A(1)Rs, determined by radioligand binding, Western blotting and
      real-time PCR assays, were significantly increased in PiD samples, suggesting up
      regulation of this receptor. AC activity was determined in basal and stimulated
      conditions via stimulatory guanine nucleotide binding proteins (Gs) using GTP, or
      directly with forskolin. Basal AC activity was reduced in brains from PiD cases.
      This agrees with the decrease in AC type I (AC I) level detected by Western
      blotting. However, inhibition of forskolin-stimulated AC activity by a selective
      A(1)R agonist was significantly increased in brains from PiD. In occipital
      cortex, adenosine A(1)R numbers were similar in control and PiD cases, and no
      significant differences were found in A(1)R-mediated AC inhibition. These results
      show that the adenosine A(1)R-AC transduction pathway is specifically up
      regulated and sensitized in frontal cortex brain in PiD.

PMID- 18052974
TI  - Short light-dark cycles affect sleep in mice.
AB  - Environmental light has a strong impact on human physiology and behaviour,
      including cognitive functioning and alertness. Previous studies have shown that
      short light-dark (LD) cycles influence sleep in the albino rat. Rapid eye
      movement (REM) sleep increases after the onset of darkness and increases after
      light onset. In the present study, we investigated whether light affects sleep in
      mice. To this purpose the electroencephalogram and electromyogram of nine adult
      male C57BL/6 mice was recorded under 12 : 12 h baseline LD conditions, followed
      by 24 h continuous darkness (DD) and 6 days with LD cycles of different durations
      (2 h, 30 min, 14 min, 10 min, 4 min and 2 min), presented in a randomized order.
      NREM sleep was evenly distributed over the light and dark intervals of all short
      LD cycles. REM sleep, however, was increased during the dark intervals of short
      (10-30 min) LD cycles. Analysis showed that in these LD cycles, the increment in
      REM sleep was maximal in the second minute after dark onset, where the percentage
      of epochs with REM sleep increased significantly to 175% of baseline values. This
      increase was attributable to an increase in REM sleep episode duration. The
      recorded responses show that sleep in mice is affected by photic stimulation. The
      results demonstrate that pigmented animals can show REM sleep induction after
      dark onset and indicate that light has significant effects on the regulation of
      sleep.

PMID- 18052975
TI  - Epileptiform synchronization in the rat insular and perirhinal cortices in vitro.
AB  - The hippocampus plays a primary role in temporal lobe epilepsy, a common form of
      partial epilepsy in adults. Recent studies, however, indicate that
      extrahippocampal areas such as the perirhinal and insular cortices represent
      important participants in this epileptic disorder. By employing field potential
      recordings in the in vitro 4-aminopyridine model of temporal lobe epilepsy, we
      have investigated here the contribution of glutamatergic and GABAergic signaling
      to epileptiform activity in these structures. First, we provide evidence of
      epileptiform synchronicity between the perirhinal and insular cortices, and
      resolve some pharmacological and network mechanisms involved in sustaining the
      interictal- and ictal-like discharges recorded there. Second, we report that in
      the absence of ionotropic glutamatergic transmission, GABAergic networks produce
      synchronous potentials that spread between the perirhinal and insular cortices.
      Finally, we have established that such activity is modulated by activating micro
      opioid receptors. Our findings support clinical and experimental evidence
      concerning the involvement of the perirhinal and insular cortex networks in
      temporal lobe epilepsy, and provide observations that may impact research
      focussing on the role of the insular cortex in nociception.

PMID- 18052976
TI  - Developmental changes in the BDNF-induced modulation of inhibitory synaptic
      transmission in the Kolliker-Fuse nucleus of rat.
AB  - The Kolliker-Fuse nucleus (KF), part of the pontine respiratory group, is
      involved in the control of respiratory phase duration, and receives both
      excitatory and inhibitory afferent input from various other brain regions. There
      is evidence for developmental changes in the modulation of excitatory inputs to
      the KF by the neurotrophin brain-derived neurotrophic factor (BDNF). In the
      present study we investigated if BDNF exerts developmental effects on inhibitory
      synaptic transmission in the KF. Recordings of inhibitory postsynaptic currents
      (IPSCs) in KF neurons in a pontine slice preparation revealed general
      developmental changes. Recording of spontaneous and evoked IPSCs (sIPSCs, eIPSCS)
      revealed that neonatally the gamma-aminobutyric acid (GABA)ergic fraction of
      IPSCs was predominant, while in later developmental stages glycinergic
      neurotransmission significantly increased. Bath-application of BDNF significantly
      reduced sIPSC frequency in all developmental stages, while BDNF-mediated
      modulation on eIPSCs showed developmental differences. The eIPSCs mean amplitude
      was uniformly and significantly reduced following BDNF application only in
      neurons from rats younger than postnatal day 10. At later postnatal stages the
      response pattern became heterogeneous, and both augmentations and reductions of
      eIPSC amplitudes occurred. All BDNF effects on eIPSCs and sIPSCs were reversed
      with the tyrosine kinase receptor-B inhibitor K252a. We conclude that
      developmental changes in inhibitory neurotransmission, including the BDNF
      mediated modulation of eIPSCs, relate to the postnatal maturation of the KF. The
      changes in BDNF-mediated modulation of IPSCs in the KF may have strong
      implications for developmental changes in synaptic plasticity and the adaptation
      of the breathing pattern to afferent inputs.

PMID- 18052977
TI  - Basolateral amygdala inactivation by muscimol, but not ERK/MAPK inhibition,
      impairs the use of reward expectancies during working memory.
AB  - Rats were trained on a delayed matching to position (DMTP) task that embedded
      either a differential outcomes procedure (DOP) or a non-differential outcomes
      procedure (NOP). The DOP, via Pavlovian conditioning (stimulus-outcome
      associations), results in the use of unique reward expectancies that facilitate
      learning and memory performance above subjects trained with a NOP that requires
      subjects to retain cue information for accurate choice behavior (stimulus
      response associations). This enhancement in learning and/or memory produced by
      the DOP is called the differential outcomes effect (DOE). After being trained on
      the DMTP task, rats were implanted with two cannulae aimed at the basolateral
      amygdala (BLA) nuclei. Rats trained with the DOP, relative to those trained with
      the NOP, displayed enhanced short-term memory (STM) performance under vehicle
      conditions (i.e. the DOE). However, injections of the gamma-aminobutyric acid
      (GABA)(A) agonist muscimol into the BLA dose-dependently (0.0625 and 0.125
      microg) impaired STM performance only in DOP-trained rats. These results support
      the role of the BLA in the use of established reward expectancies during a short
      term working memory task. Despite the fact that extracellular signal-regulated
      kinase/mitogen-activated protein kinases (ERK/MAPK) have been shown to be
      necessary for amygdala-dependent long-term potentiation and some forms of long
      term and STM, inhibition of the ERK/MAPK signaling cascade by U0126 (2.0 or 4.0
      microg) in the BLA was not critical for updating the STM of either spatial
      information or reward expectation.

PMID- 18052978
TI  - Olfactory bulb hypoplasia in Prokr2 null mice stems from defective neuronal
      progenitor migration and differentiation.
AB  - New neurons are added on a daily basis to the olfactory bulb (OB) of a mammal,
      and this phenomenon exists throughout its lifetime. These new cells are born in
      the subventricular zone and migrate to the OB via the rostral migratory stream
      (RMS). To examine the role of the prokineticin receptor 2 (Prokr2) in
      neurogenesis, we created a Prokr2 null mouse, and report a decrease in the volume
      of its OB and also a decrease in the number of bromodeoxyuridine (BrdU)-positive
      cells. There is disrupted architecture of the OB, with the glomerular layer
      containing terminal dUTP nick-end labeling (TUNEL) -positive nuclei and also a
      decrease in tyrosine hydroxylase-positive neurons in this layer. In addition,
      there are increased numbers of doublecortin-positive neuroblasts in the RMS and
      increased PSA-NCAM (polysialylated form of the neural cell adhesion molecule) 
      positive neuronal progenitors around the olfactory ventricle, indicating their
      detachment from homotypic chains is compromised. Finally, in support of this,
      Prokr2-deficient cells expanded in vitro as neurospheres are incapable of
      migrating towards a source of recombinant human prokineticin 2 (PROK2). Together,
      these findings suggest an important role for Prokr2 in OB neurogenesis.

PMID- 18052979
TI  - Influence of macrophages and lymphocytes on the survival and axon regeneration of
      injured retinal ganglion cells in rats from different autoimmune backgrounds.
AB  - The immune response after neural injury influences the survival and regenerative
      capacity of neurons. In the primary visual pathway, previous studies have
      described beneficial effects of macrophages and T-cells in promoting neural
      survival and axonal regeneration in some rat strains. However, the contributions
      of specific cell populations to these responses have been unclear. In adult
      Fischer (F344) rats, we confirm prior reports that intravitreal macrophage
      activation promotes the survival of retinal ganglion cells (RGCs) and greatly
      enhances axonal regeneration through a peripheral nerve graft. Neonatal
      thymectomy that results in elimination of T-cell production enhanced RGC survival
      after axotomy, but diminished the effect of intravitreal macrophage activation on
      axon regeneration. Thus, in F344 rats, lymphocytes appear to suppress RGC
      survival but augment the pro-regenerative effects of macrophages. The cytotoxic
      effect of lymphocytes on RGCs was confirmed in in vitro studies; coculture of
      retinal explants with lymphocytes led to a 60% reduction in viable RGCs. Similar
      in vivo results were obtained in Sprague Dawley rats. By comparison, in adult
      Lewis rats, neither RGC survival nor axonal regeneration was increased after
      intravitreal macrophage activation. Neonatal thymectomy had only a small
      beneficial effect on RGC survival, and although Lewis lymphocytes reduced RGC
      viability in culture, they did so to a lesser extent. Thus, in addition to a
      complex role of lymphocytes, particularly T-cells, after central nervous system
      injury, the present results demonstrate that the impact of macrophages is also
      influenced by genetic background.

PMID- 18052980
TI  - A potential role for calcium / calmodulin-dependent protein kinase-related
      peptide in neuronal apoptosis: in vivo and in vitro evidence.
AB  - Previously, we have established that a product of the doublecortin-like kinase
      (DCLK) gene, DCLK-short, is cleaved by caspases during serum deprivation.
      Subsequently, the N-terminal cleavage product of DCLK-short facilitates apoptosis
      in the neuroblastoma cell line NG108. As this N-terminal cleavage product is
      highly homologous to calcium/calmodulin-dependent protein kinase-related peptide
      (CARP), another DCLK gene splice variant, we aimed to determine the possible
      apoptotic properties of CARP in vivo and in vitro. We report highly specific CARP
      expression in apoptotic granule cells in the rat dentate gyrus after
      adrenalectomy relative to healthy granule cells. CARP is significantly
      upregulated in the suprapyramidal blade of the dentate gyrus, with varying levels
      of upregulation, depending on the extent of adrenalectomy-induced apoptosis.
      Similar to the caspase-cleaved N-terminus of DCLK-short, CARP overexpression
      itself facilitated apoptosis in serum-deprived NG108 cells. Furthermore, CARP
      facilitated polymerization of tubulin in vitro and was capable of interacting
      with growth factor receptor-bound protein 2, an intracellular protein involved in
      vesicle trafficking. Together, our data demonstrate a facilitating role for CARP
      in the apoptotic process in granule cell populations sensitive to adrenalectomy,
      and suggest that this proapoptotic effect is mediated by increasing the stability
      of the microtubule cytoskeleton.

PMID- 18052981
TI  - Site-specific effects of tau phosphorylation on its microtubule assembly activity
      and self-aggregation.
AB  - Microtubule-associated protein tau is abnormally hyperphosphorylated and
      aggregated into neurofibrillary tangles in brains with Alzheimer's disease. The
      phosphorylation sites of tau are mainly localized in the proline-rich (residues
      172-251) and C-terminal tail (residues 368-441) regions, which flank the
      microtubule-binding repeats. Here, we investigated the effects of tau
      phosphorylation at these distinct sites/regions on its activity of stimulating
      microtubule assembly and its self-aggregation. We found that tau phosphorylation
      at the proline-rich region by dual-specificity tyrosine-phosphorylated and 
      regulated kinase 1A inhibited its microtubule assembly activity moderately and
      promoted its self-aggregation slightly. Tau phosphorylation at the C-terminal
      tail region by glycogen synthase kinase-3beta increased its activity and promoted
      its self-aggregation markedly. Tau phosphorylation at both regions plus the
      microtubule-binding region by cAMP-dependent protein kinase diminished its
      activity (approximately 70% inhibition) and disrupted microtubules. These studies
      reveal the differential regulation of tau's biological activity and self
      aggregation by phosphorylation at various sites/regions.

PMID- 18052982
TI  - Target regulation of V2R expression and functional maturation in vomeronasal
      sensory neurons in vitro.
AB  - Vomeronasal receptors from the V1R and V2R gene families mediate the detection of
      chemical stimuli such as pheromones via the vomeronasal organ (VNO). The
      differential expression of vomeronasal receptors might contribute in part to a
      variety of pheromonal effects, which are different sexually, developmentally and
      even individually. However, little is known about the mechanisms controlling
      vomeronasal receptor expression. Cultured vomeronasal sensory neurons (VSNs) bear
      phenotypic resemblance to the intact VNO but they remain immature. Because
      indices of VSN maturation are increased by coculture with the target cells for
      VSNs, accessory olfactory bulb (AOB) neurons, AOB neurons may regulate
      vomeronasal receptor expression and functional maturation in VSNs. To test this
      hypothesis, we examined the expression of V2R-type vomeronasal receptors (VR1 and
      VR4) and chemosensory responsiveness in VNOs cocultured with AOB neurons.
      Immunoblot and immunocytochemical analysis revealed that the coculture of VNOs
      with AOB neurons resulted in a greater expression of VR1 and VR4 after 10 days
      than VNOs cultured alone. Moreover, calcium imaging analysis showed that
      cocultured VNOs responded to urine components applied iontophoretically into
      their cavities with a time course similar to the V2R expression, in contrast to
      singly cultured VNOs that displayed no response. These results demonstrate that
      AOB neurons induce the expression of vomeronasal receptors in VSNs, allowing them
      to function.

PMID- 18052983
TI  - Adenosine A1 receptor-mediated inhibition of dopamine release from rat striatal
      slices is modulated by D1 dopamine receptors.
AB  - Dopamine release is regulated by presynaptic dopamine receptors and interactions
      between adenosine and dopamine receptors have been well documented. In the
      present study, dopamine release from isolated striatal slices from Wistar rats
      was measured using fast cyclic voltammetry. Single-pulse stimulation (0.1 ms, 10
      V) was applied every 5 min over a 2-h period. Superfusion with the adenosine
      (A)(1) receptor agonist N(6)-cyclopentyladenosine (CPA), but not the A(2)
      receptor agonist 3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4
      dihydroxy-oxolan-2-yl]purin-2-yl]amino]ethyl] phenyl]propanoic acid (CGS 21680),
      inhibited dopamine release in a concentration-dependent manner (IC(50) 3.80 x 10(
      7) m; n = 10). The dose-response curve to CPA was shifted to the right (IC(50)
      6.57 x 10(-6) m; n = 6, P < 0.05 vs. control) by the A(1) receptor antagonist 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX). Neither the D(1) agonist 6-chloro-APB
      nor the D(1) antagonist R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-
      benzazepine-7-ol (SCH 23390) altered dopamine release on their own. However, SCH
      23390 (3 microm) significantly attenuated the response to CPA (IC(50) 1.44 x 10(
      5) m; n = 6, P < 0.01 vs. control). Furthermore, the inhibitory effect of CPA was
      significantly increased in the presence of 6-chloro-APB (1 microm). In
      radioligand binding experiments, CPA interacted with high- and low-affinity
      states of [(3)H]DPCPX-lableled A(1) receptors. The high-affinity agonist binding
      to A(1) receptors was inhibited by the stable guanosine triphosphate analogue
      Gpp(NH)p. In contrast, neither the proportion nor the affinity of high-affinity
      A(1) receptors was altered by dopamine or SCH 23390. These results provide
      evidence that the inhibition of dopamine release by adenosine A(1) receptors is
      dependent, at least in part, on the simultaneous activation of D(1) dopamine
      receptors. While the mechanism underlying this interaction remains to be
      determined, it does not appear to involve an intramembrane interaction between
      A(1) and D(1) receptors.

PMID- 18052984
TI  - The transcriptional corepressor TPA-inducible sequence 7 regulates adult axon
      growth through cellular retinoic acid binding protein II expression.
AB  - TPA-inducible sequence 7 (TIS7) expression is regulated in epithelial cells and
      acts as a transcriptional corepressor. Using a TIS7 knock-out mouse we
      demonstrated that TIS7 is involved in the process of muscle regeneration. In this
      study, we analysed the role of TIS7 in axon regeneration, applying primary
      neurone cultures derived from adult dorsal root ganglia (DRGs) of TIS7+/+ and
      TIS7-/- mice. TIS7-/- DRG neurones exhibited a significant decrease in axon
      initiation and maximal axon extension. In contrast, nerve growth factor-induced
      axon initiation and branching were significantly enhanced in cultures obtained
      from TIS7-/- DRGs when compared with wildtype ganglia, suggesting an inhibitory
      effect of TIS7 on nerve growth factor-stimulated axon growth. TIS7 overexpression
      in TIS7-/- DRG neurones caused their morphological appearance to revert back to
      the wildtype phenotype. Furthermore, the expression of cellular retinoic acid
      binding protein II (CRABP II), previously identified by us as a TIS7 target gene,
      was up-regulated in adult DRG sensory neurones from TIS7-/- mice. Overexpression
      of CRABP II in TIS7+/+ neurones strongly increased the number of branch points,
      making them morphologically similar to TIS7-/- neurones. Based on these results
      we propose that TIS7 inhibits CRABP II expression during axonal regeneration,
      thereby modulating retinoic acid signalling. Hence, neurite initiation and
      branching are regulated by a negative feedback mechanism involving TIS7 and CRABP
      II.

PMID- 18052985
TI  - X chromosome-linked inhibitor of apoptosis protein reduces oxidative stress after
      cerebral irradiation or hypoxia-ischemia through up-regulation of mitochondrial
      antioxidants.
AB  - We demonstrate that X chromosome-linked inhibitor of apoptosis protein (XIAP)
      counteracts oxidative stress in two essentially different disease-related models
      of brain injury, hypoxia-ischemia and irradiation, as judged by lower expression
      of nitrotyrosine (5-fold) and 4-hydroxy-2-nonenal (10-fold) in XIAP
      overexpressing compared with wild-type mice. XIAP overexpression induced up
      regulation of at least three antioxidants residing in mitochondria, superoxide
      dismutase 2, thioredoxin 2 and lysine oxoglutarate reductase. Cytochrome c
      release from mitochondria was reduced in XIAP-overexpressing mice. Hence, in
      addition to blocking caspases, XIAP can regulate reactive oxygen species in the
      brain, at least partly through up-regulation of mitochondrial antioxidants. XIAP
      induced prevention of oxidative stress was not secondary to tissue protection
      because although XIAP overexpression provides tissue protection after hypoxia
      ischemia, it does not prevent tissue loss after irradiation. This is a previously
      unknown role of XIAP and may provide the basis for development of novel
      protective strategies for both acute and chronic neurodegenerative diseases,
      where oxidative stress is an integral component of the injury mechanisms
      involved.

PMID- 18052986
TI  - Monocular deprivation reduces reliability of visual cortical responses to
      binocular disparity stimuli.
AB  - While continuous monocular deprivation (MD) of patterned vision causes severe
      loss of visual cortical responses and visual acuity in the affected eye, these
      effects can be avoided by providing brief daily periods of binocular exposure
      [BE; D.E. Mitchell et al. (2003) Curr. Biol., 8, 1179-1182; D.E. Mitchell et al.
      (2006) Eur. J. Neurosci., 23, 2458-2466; D.S. Schwarzkopf et al. (2007) Eur. J.
      Neurosci., 25, 270-280]. In order to analyse binocular mechanisms involved in
      this phenomenon, we studied neuronal responses in primary visual cortex to
      binocular disparity stimuli in cats that had experienced mixed daily visual
      exposure (i.e. different amounts of daily binocular and monocular exposure). To
      examine whether binocular responses are as reliable in MD as in normal animals,
      we analysed single-trial responses to spatial phase disparity stimuli. In cats
      with various amounts of daily binocular experience (3.5 h, 7 h or 12 h) alone,
      about half of neurons (47.9%) showed reliable phase-specific binocular responses
      in two consecutive trials. The percentage of phase-selective cells was reduced in
      cats with mixed visual exposure with a decrease in the duration of daily BE.
      Within these neurons, a 'stable' cell population, i.e. with identical relative
      phases eliciting the strongest and weakest responses in two trials, was also
      reduced. In other words, the responses of neurons recorded from deprived animals
      were more likely to show different preferred phases on successive trials,
      although their amplitude ratios in both trials were about equal. We suggest that
      the detrimental effect of MD on binocular vision may begin, at least in part,
      with a subtle disruption of the mechanism involved in discrimination of binocular
      disparity signals.

PMID- 18052987
TI  - Calpain-mediated cleavage of collapsin response mediator protein(CRMP)-2 during
      neurite degeneration in mice.
AB  - Axon or dendrite degeneration involves activation of the ubiquitin-proteasome
      system, failure to maintain neuritic ATP levels, microtubule fragmentation and a
      mitochondrial permeability transition that occur independently of the somal death
      programs. To gain further insight into the neurite degeneration mechanims we have
      compared two-dimensional gel electrophoresis patterns of neurite proteins from
      suprior cervical ganglia during degeneration caused by nerve growth factor (NGF)
      deprivation. We show here that collapsin response mediator protein (CRMP)-2 and
      CMRP-4 protein patterns were altered during beading formation, an early hallmark
      of neurite degeneration, prior to neurite fragmentation, the final stage of
      degeneration. Western blotting using a monoclonal antibody against CRMP-2 shows
      that the native form (64 kDa) was cleaved to generate a truncated form (58 kDa).
      No cleavage of CRMP-2 or -4 occurred in NGF-deprived neurites from Wld(s)
      (Wallerian degeneration slow) mutant mice in which neurite degeneration is
      markedly delayed. Using different protease inhibitors, purified calpain 1 protein
      and calpain 1-specific siRNA, we have demonstrated that CRMP-2 is a substrate for
      calpain 1. Indeed, caplain activity was activated at an early phase of neuronal
      degeneration in cerebellar granule neurons, and down-regulation of caplain 1
      expression suppressed CRMP-2 cleavage. Furthermore, this cleavage occurred after
      vinblastine treatment or in vitro Wallerian degeneration, suggesting that it
      represents a common step in the process of dying neurites. CRMP-2 and -4 play a
      pivotal role in axonal growth and transport, and the C-terminus region of CRMP-2
      is essential for its binding to kinesin-1. Hence, this cleavage will render them
      dysfunctional and subject to autophagic processing associated with beading
      formation, as evidenced by the finding that the truncated form was localized in
      the beadings.

PMID- 18052988
TI  - Modulation of human corticomuscular beta-range coherence with low-level static
      forces.
AB  - Although corticomuscular synchronization in the beta range (15-30 Hz) was shown
      to occur during weak steady-state contractions, an examination of low-level
      forces around 10% of the maximum voluntary contraction (MVC) is still missing. We
      addressed this question by investigating coherence between electroencephalogram
      (EEG) and electromyogram (EMG) as well as cortical spectral power during a
      visuomotor task. Eight healthy right-handed subjects compensated isometrically
      static forces at a level of 4% and 16% of MVC with their right index finger.
      While 4% MVC was accompanied by low coherence values in the middle to high beta
      frequency range (25-30 Hz), a significant increase of coherence mainly confined
      to low beta frequencies (19-20 Hz) was observed with force of 16% MVC.
      Furthermore, this increase was associated with better performance, as reflected
      in decreased relative error in force during 16% MVC. We additionally show that
      periods of good motor performance within each condition were associated with
      higher values of EEG-EMG coherence and spectral power. In conclusion, our results
      suggest a role for beta-range corticomuscular coherence in effective sensorimotor
      integration, thus stabilizing corticospinal communication.

PMID- 18052989
TI  - Axonal projections of single auditory neurons in the thalamic reticular nucleus:
      implications for tonotopy-related gating function and cross-modal modulation.
AB  - Tonotopically comparable subfields of the primary auditory area (AI) and
      nonprimary auditory areas (non-AI), i.e. posterodorsal area (PD) and ventral
      auditory area (VA), in the rat cortex have similar topographies in the projection
      to the ventral division of the medial geniculate nucleus (MGV), but reverse
      topographies in the projection to the thalamic reticular nucleus (TRN). In this
      study, we examined axonal projections of single auditory TRN cells, using
      juxtacellular recording and labeling techniques, to determine features of TRN
      projections and estimate how the TRN mediates corticofugal inhibition along with
      the reverse topographies of cortical projections to the TRN. Auditory TRN cells
      sent topographic projections to limited parts of the MGV in a manner that relays
      cortical inputs from tonotopically comparable subfields of the AI and non-AI (PD
      and VA) to different parts of the MGV. The results suggest that corticofugal
      excitations from the AI and non-AI modulate thalamic cell activity in the same
      part of the MGV, whereas corticofugal inhibitions via the TRN modulate cell
      activity in different parts of the MGV with regard to tonotopic organization. The
      AI and non-AI could serve distinctive gating functions for auditory attention
      through the differential topography of inhibitory modulation. In addition, we
      obtained an intriguing finding that a subset of auditory TRN cells projected to
      the somatosensory but not to the auditory thalamic nuclei. There was also a cell
      projecting to the MGV and somatosensory nuclei. These findings extend the
      previously suggested possibility that TRN has a cross-modal as well as an
      intramodal gating function in the thalamus.

PMID- 18052990
TI  - CB1 receptor-mediated control of the release of endocannabinoids (as assessed by
      microdialysis coupled with LC/MS) in the rat hypothalamus.
AB  - In the present study, we examined the occurrence and potential regulation of
      endocannabinoid release by cannabinoid CB1 receptors in the rat brain. To this
      end, we developed a highly sensitive (limit of sensitivity 30-300 amol) new
      analytical method, combining online brain microdialysis with solid-phase
      extraction-liquid chromatography-tandem mass spectrometry, which allowed the
      detection in real time of trace amounts of endocannabinoids in the extracellular
      fluid. In the hypothalamus, anandamide and 2-arachidonoyl-glycerol release was
      stimulated following depolarization via local administration of K(+), with or
      without addition of Ca(2+), or glutamate application. Inhibition of fatty acid
      amide hydrolase by systemic administration of intraperitoneal (i.p.) URB597 (0.5
      mg/kg) induced an increase of anandamide, but not 2-arachidonoyl-glycerol,
      outflow. The CB1 receptor antagonist rimonabant (10 mg/kg i.p.) increased,
      whereas the CB1 agonist WIN55,212-2 (2.5 mg/kg i.p.) decreased, anandamide
      release. Interestingly, the same treatments induced opposite changes in 2
      arachidonoyl-glycerol release. At a dose of 3 mg/kg i.p., which by itself did not
      affect endocannabinoid release, rimonabant fully antagonized the effect of
      WIN55,212-2 (2.5 mg/kg i.p.). Taken together, these results suggest that CB1
      receptors are able to control the local release of endocannabinoids in the
      hypothalamus via a feedback mechanism and strengthen the view that anandamide and
      2-arachidonoyl-glycerol have distinct physiological roles.

PMID- 18052991
TI  - Skin conductance compared to a combined behavioural and physiological pain
      measure in newborn infants.
AB  - AIM: To assess the ability of galvanic skin response (GSR) to differentiate
      between tactile and painful stimulation in newborn infants, and to compare this
      with the ability of the premature infant pain profile (PIPP). METHODS: Thirty-two
      healthy full-term infants undergoing routine blood sampling were recruited. In a
      randomized order they were subjected to tactile and painful stimulation. The
      three GSR variables conductance baseline level, number of waves per second and
      mean amplitude of the waves were recorded together with the behavioural and
      physiological variables of PIPP. RESULTS: The GSR variables number of waves and
      amplitude of the waves increased more during painful stimulation than during
      tactile stimulation, as did also the PIPP score. Receiver operating
      characteristic curves analysis revealed no significant differences between the
      studied methods. CONCLUSION: GSR can differentiate painful from tactile
      stimulation, but more research is needed to achieve a clinically useful
      application.

PMID- 18052992
TI  - Can we reduce episodes of haemoglobin desaturation in full-term babies restrained
      in car seats?
AB  - OBJECTIVES: To determine whether episodes of haemoglobin oxygen (SpO2)
      desaturation in full-term infants restrained in car seats can be reduced by a
      simple foam plastic infant car seat insert designed to push the body forward,
      with space for the protuberant occiput to lie behind the spine, and so reduce
      flexion of the infant's head on the trunk. METHODS: Eighteen healthy full-term
      babies were evaluated while restrained in an infant car safety seat with, and
      without, the foam insert. Infants were monitored in each position for 30 min with
      continuous polygraphic recording of respiratory and heart rate, nasal airflow and
      SpO2. RESULTS: Placement of the insert in the car seat was associated with a
      significant reduction in the rate of apneas with a fall in SpO2 >5% (median,
      interquartile range: 4.4 (0, 10.6) vs. 9.2 (5.4, 15.2) events per hour, p=0.03).
      The one clinically severe episode of apnea, with a fall in SpO2 of more than 30%,
      occurred in the car seat without the insert. CONCLUSIONS: A car seat insert that
      allows the newborn's head to lie in a neutral position during sleep may reduce
      the frequency of mild episodes of reduced SpO2 in some full-term newborn babies.

PMID- 18052993
TI  - Catecholaminergic polymorphic ventricular tachycardia in a child: a case report.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare
      arrythmogenic disease characterized by exercise--or stress--induced ventricular
      tachyarrythmias, syncope, or sudden death, usually in the pediatric age group.
      Familial occurrence has been noted in about 30% of cases. Inheritance may be
      autosomal dominant or recessive, usually with high penetrance. The causative
      genes have been mapped to chromosome 1. Mutations of the cardiac ryanodine
      receptor gene (RyR2) have been identified in autosomal dominant pedigrees, while
      calsequestrin gene (CASQ2) mutations are seen in recessive cases. CONCLUSION: Due
      to its potential lethal outcome, exclusion or confirmation of catecholaminergic
      polymorphic ventricular tachycardia in children with physical and emotional
      syncope is mandatory. We report a case of catecholaminergic polymorphic
      ventricular tachycardia in a three-year-old child only diagnosed by genetic
      mapping.

PMID- 18052994
TI  - A visual pitfall: persistent Mullerian duct syndrome (PMDS).
AB  - Persistent Mullerian Duct Syndrome (PMDS) is a rare disorder of the anti
      mullerian hormone (AMH) synthesis or receptor, which due to the visual contrast
      of normal masculine external genitalia and female internal genitalia can raise
      confusion, sometimes during surgery for cryptorchidism or hernia inguinalis. For
      an acute and accurate analysis of such a situation a thorough knowledge of
      gonadal embryology is mandatory. The diagnosis is made on finding Mullerian
      structures in an individual with complete virilization without signs of
      hypocortisolism or exposition to maternal androgens during foetal life.
      Karyotyping and gonadal biopsy provide additional information to confirm the
      diagnosis. As the risk of malignant transformation is not clear, orchidopexy is
      advised in patients with cryptorchidism, with lifelong palpatory follow-up. In
      case of urologic symptoms, surgical removal of the Mullerian remnants can be
      considered, with careful attention for the vulnerable ductus deferens. Despite
      optimal treatment the prognosis regarding fertility remain uncertain.

PMID- 18052995
TI  - Fathers' involvement and children's developmental outcomes: a systematic review
      of longitudinal studies.
AB  - OBJECTIVE: This systematic review aims to describe longitudinal evidence on the
      effects of father involvement on children's developmental outcomes. METHODS:
      Father involvement was conceptualized as accessibility (cohabitation),
      engagement, responsibility or other complex measures of involvement. Both
      biological fathers and father figures were included. We searched all major
      databases from the first dates. Data on father involvement had to be generated at
      least 1 year before measuring offspring outcomes. RESULTS: N = 24 publications
      were included in the overview: 22 of these described positive effects of father
      involvement, whereof 16 studies had controlled for SES and 11 concerned the study
      population as a whole [five socio-economic status (SES)-controlled]. There is
      certain evidence that cohabitation with the mother and her male partner is
      associated with less externalising behavioural problems. Active and regular
      engagement with the child predicts a range of positive outcomes, although no
      specific form of engagement has been shown to yield better outcomes than another.
      Father engagement seems to have differential effects on desirable outcomes by
      reducing the frequency of behavioural problems in boys and psychological problems
      in young women, and enhancing cognitive development, while decreasing delinquency
      and economic disadvantage in low SES families. CONCLUSIONS: There is evidence to
      support the positive influence of father engagement on offspring social,
      behavioural and psychological outcomes. Although the literature only provides
      sufficient basis for engagement (direct interaction with the child) as the
      specific form of 'effective' father involvement, there is enough support to urge
      both professionals and policy makers to improve circumstances for involved
      fathering.

PMID- 18052996
TI  - Risk factors for early sepsis in very low birth weight neonates with respiratory
      distress syndrome.
AB  - AIM: To identify maternal and neonatal factors that increase suspicion of early
      sepsis in Very Low Birth Weight neonates with respiratory distress syndrome.
      METHODS: The cohort included 282 neonates born at Soroka Medical Centre 1996
      2000. Definitions of 'high' and 'low'-suspicion groups for early sepsis were
      based on comparison between neonates with early sepsis and the remaining cohort.
      Univariate analysis and logistic regression were used to compare between groups.
      RESULTS: The incidence of early sepsis in the cohort was 1.8%, and 94% received
      antibiotics following delivery. Comparing with the remaining cohort, the five
      neonates with early sepsis had increased incidence of positive maternal cultures,
      use of antenatal antibiotics, lower 1 min Apgar scores and tendency to
      leucopenia. A 'low-suspicion' group comprised 38% of the cohort and did not
      include any neonates with early sepsis. This group were more frequently treated
      with antenatal steroids and delivered by Caesarean section compared to the 'high
      suspicion' group, but otherwise there were no clinical and laboratory
      differences. CONCLUSION: Although the incidence of early sepsis is low almost all
      neonates received antibiotics. A 'low-suspicion' group was defined and the role
      of antibiotic treatment in this group needs to be determined.

PMID- 18052997
TI  - Erythropoietin inhibits cytokine production of neonatal and adult leukocytes.
AB  - BACKGROUND: Erythropoietin (Epo) was originally defined as a hematopoietic growth
      factor, but also has potent tissue-protective properties. The cytokine-modulating
      actions of Epo have received scant attention. We hypothesized that Epo
      significantly influences the in vitro cytokine production in both neonates and
      adults. METHODS: The effects of Epo were investigated using a standardized in
      vitro whole blood assay. Production of various cytokines was assessed by means of
      intracellular cytokine detection (IL-2, -6, -8, IFN-gamma and TNF-alpha) in
      preterm infants, term neonates and adults. Furthermore, synthesis of IL-4, -5 and
      -10 in adults was investigated via cytometric bead array. RESULTS: Epo
      significantly inhibits the production of various cytokines in preterm infants,
      term neonates and adults. In CD3+ lymphocytes, Epo predominantly decreases the
      number of IL-2-positive cells in all age groups. Similarly, in CD14+ cells, Epo
      significantly diminishes the number of IL-6- and TNF-alpha-producing cells.
      Furthermore, Epo significantly inhibits the synthesis of IL-4, IL-5 and IL-10 in
      adults. CONCLUSION: rhEpo has significant inhibitory potential on the production
      of various cytokines by leukocytes in preterm and term infants as well as in
      adults. The described effect likely contributes to the tissue protective
      properties of Epo.

PMID- 18052998
TI  - Wheezy babies--wheezy adults? Review on long-term outcome until adulthood after
      early childhood wheezing.
AB  - Population-based birth cohort studies have documented that about 30% of children
      suffer from wheezing during respiratory infection before their third birthday.
      Recurrent wheezing is common in early childhood, but most patients outgrow their
      symptoms by school age. However, recent long-term postbronchiolitis follow-up
      studies from Sweden and Finland have revealed that asthma is present in about 40%
      of young adults and over half of the cases are relapses after many symptom-free
      years. In population studies, the principal predictors for later asthma have been
      parental asthma, recurrent wheezing, atopy and eosinophilia. In the Swedish
      postbronchiolitis study, atopic diathesis through the development of clinical
      atopy, and early passive smoking through bronchial hyper-reactivity or later
      active smoking led to adult asthma. The Finnish postbronchiolitis follow-up
      stressed early recurrence of wheezing, wheezing induced by less invasive viruses
      than respiratory syncytial virus (RSV), early-life atopy and eosinophilia and
      parental asthma as predictors for adult asthma. CONCLUSION: The majority of
      wheezing infants and children outgrow their symptoms by school age, but based on
      recent long-term follow-up studies, asthma relapses are common in young adults.
      These studies have highlighted parental asthma, maternal smoking and wheezing
      induced by other viruses than RSV as predictive factors for later asthma.

PMID- 18053000
TI  - Promotion of exclusive breastfeeding is not likely to be cost effective in West
      Africa. A randomized intervention study from Guinea-Bissau.
AB  - AIM: To evaluate the impact of promotion of exclusive breastfeeding on infant
      health in Guinea-Bissau, West Africa, where mortality rates are high,
      breastfeeding is widely practiced but exclusive breastfeeding is rare. METHOD: At
      the Bandim Health Project in Guinea Bissau, West Africa, a birth cohort of 1721
      infants were randomized to receive health education: promotion of exclusive
      breastfeeding for the first 4-6 months of life according to WHO recommendations
      at the time of the study. All children were followed from birth to 6 months of
      age. RESULTS: Introduction of both water and weaning food was significantly
      delayed in the intervention group. However we found no beneficial health effects
      of the intervention; there was no reduction in mortality in the intervention
      group compared with the control group (mortality rate ratio: 1.86 (0.79-4.39)),
      weight at 4-6 months of age was significantly lower in the intervention group
      (7.10 kg vs. 7.25 kg; Wilcoxon two-sample test: p=0.03). There was no difference
      in diarrhoea morbidity and hospitalization rates. CONCLUSION: Although mothers
      were sensitive to follow new breastfeeding recommendations, it had no beneficial
      impact on infant health in this society with traditional, intensive
      breastfeeding. There seems to be little reason to discourage local practices as
      long as there are no strong data justifying such a change.

PMID- 18052999
TI  - Maturation of oral feeding skills in preterm infants.
AB  - AIM: Safe and successful oral feeding requires proper maturation of sucking,
      swallowing and respiration. We hypothesized that oral feeding difficulties result
      from different temporal development of the musculatures implicated in these
      functions. METHODS: Sixteen medically stable preterm infants (26 to 29 weeks
      gestation, GA) were recruited. Specific feeding skills were monitored as indirect
      markers for the maturational process of oral feeding musculatures: rate of milk
      intake (mL/min); percent milk leakage (lip seal); sucking stage, rate (#/s) and
      suction/expression ratio; suction amplitude (mmHg), rate and slope (mmHg/s);
      sucking/swallowing ratio; percent occurrence of swallows at specific phases of
      respiration. Coefficients of variation (COV) were used as indices of functional
      stability. Infants, born at 26/27- and 28/29-week GA, were at similar
      postmenstrual ages (PMA) when taking 1-2 and 6-8 oral feedings per day. RESULTS:
      Over time, feeding efficiency and several skills improved, some decreased and
      others remained unchanged. Differences in COVs between the two GA groups
      demonstrated that, despite similar oral feeding outcomes, maturation levels of
      certain skills differed. CONCLUSIONS: Components of sucking, swallowing,
      respiration and their coordinated activity matured at different times and rates.
      Differences in functional stability of particular outcomes confirm that
      maturation levels depend on infants' gestational rather than PMA.

PMID- 18053001
TI  - Do parental ratings on cognition reflect neuropsychological outcome in congenital
      heart disease?
AB  - AIM: To describe the parental view of the cognitive skills of their child with a
      surgically corrected congenital heart disease (CHD) and compare it to objectified
      cognitive measures in children with CHD 6-12 years postoperatively. METHODS:
      Parents completed a questionnaire on several cognitive functions of their child.
      Children with CHD and healthy controls (n=86, aged 8 years 8 months +/- 1 year 6
      months) underwent an abbreviated IQ-testing and a neurodevelopmental assessment.
      RESULTS: Parents of the children with CHD more frequently indicated lower
      sustained attention (p<0.05), lower divided attention (p<0.001), more problems
      with memory and learning skills (p<0.05), and deficient gross motor functioning
      (p<0.01) compared to the parents of healthy controls. Intellectual and
      neuropsychological assessment revealed a lower estimated full-scale IQ (p<0.01),
      worse sensorimotor functioning (p<0.001), and lower performances on language
      (p<0.001), attention/executive functioning (p<0.05), and memory (p<0.05) in the
      CHD-group. Several items of the questionnaire were significant predictors for
      worse neurodevelopmental outcome. CONCLUSION: Overall, the objective and
      subjective measures on cognitive functioning are in agreement and indicate the
      presence of neurocognitive deficits in children with CHD. This study endorses the
      accuracy and usefulness of a parental questionnaire to report on the cognitive
      functioning of the child and urges the investigation of neurocognitive
      functioning in children with CHD at follow-up.

PMID- 18053003
TI  - Attaching effacing Escherichia coli and paradigms of Tir-triggered actin
      polymerization: getting off the pedestal.
AB  - Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC) colonize
      the gut mucosa via attaching and effacing (A/E) lesions. For years cultured cells
      were used as model systems to study A/E lesion formation, which showed actin
      accumulation under attached bacteria that can be raised above the plasma membrane
      in a pedestal-shaped structure. Studies of prototypical strains revealed that
      although both converge on N-WASP EPEC and EHEC O157:H7 use different actin
      polymerization pathways. While EPEC use the Tir-Nck pathway, Tir(EHECO157)
      cooperates with TccP/EspF(U) to activate N-WASP. However, recent in vitro studies
      revealed a common EPEC and EHEC Tir-dependent and Nck-independent inefficient
      actin polymerization pathway. Unexpectedly, bacterial populations studies
      demonstrated that most non-O157 EHEC strains and EPEC lineage 2 strains can
      utilize both the Nck and TccP2 pathways in vitro. Importantly, in vivo and ex
      vivo mucosal infections have shown efficient A/E lesion formation independently
      of Nck and TccP. This review covers the progression in our understanding of EPEC
      and EHEC infection, through the different milestones obtained using cultured
      cells, to the realization that EPEC and EHEC have much more in common than
      previously appreciated and that mucosal attachment and microvillous effacement
      may be the key events, rather than pedestal formation.

PMID- 18053002
TI  - Prevention of traumatic headache, dizziness and fatigue with creatine
      administration. A pilot study.
AB  - AIM: The complex pathobiology of traumatic brain injury (TBI) offers numerous
      targets for potential neuroprotective agents. We evaluate the clinical benefit
      after creatine (Cr) administration in children and adolescents. METHODS: A
      prospective, randomized, comparative, open- labelled pilot study of the possible
      neuroprotective effect of Cr was carried out on 39 children and adolescents, aged
      between 1 and 18 years of age, with TBI. The Cr was administered for 6 months, at
      a dose of 0.4 g/kg in an oral suspension form every day. For categorical
      variables, we used the Chi-square test to identify differences between controls
      and cases. Statistical significance was defined as a p-value <0.05 and not
      statistically significant if p-value >0.1. RESULTS: The administration of Cr to
      children and adolescents with TBI improved results in several parameters,
      including duration of post traumatic amnesia (PTA), duration of intubation,
      intensive care unit stay. Significant improvement was recorded in the categories
      of headache (p<0.001), dizziness (p=0.005) and fatigue (p<0.001), aspects in all
      patients. No side effects were seen due to Cr administration. CONCLUSION: More
      specific examinations including brain spectroscopy for in vivo evaluation of Cr
      can be done, in order to draw conclusions for the optimal duration and manner of
      Cr supply, as well as its possible role for the prevention of TBI complications,
      in double blind studies.

PMID- 18053004
TI  - The Pseudomonas aeruginosa type III secreted toxin ExoT is necessary and
      sufficient to induce apoptosis in epithelial cells.
AB  - Type III secreted (T3SS) effectors are important virulence factors in acute
      infections caused by Pseudomonas aeruginosa. PA103, a well-studied human lung
      isolate, encodes and secretes two effectors, ExoU and ExoT. ExoU is a potent
      cytotoxin that causes necrotic cell death. In addition, PA103 can induce cell
      death in macrophages in an ExoU-independent but T3SS-dependent manner. We now
      demonstrate that ExoT is both necessary and sufficient to cause apoptosis in HeLa
      cells and that it activates the mitochondrial/cytochrome c-dependent apoptotic
      pathway. We further show that ExoT induction of cell death is primarily dependent
      on its ADP ribosyltransferase domain activity. Our data also indicate that the
      T3SS apparatus can cause necrotic cell death, which is effectively blocked by
      ExoT, suggesting that P. aeruginosa may have evolved strategies to prevent T3SS
      induced necrosis.

PMID- 18053005
TI  - Gibberellins modulate light signaling pathways to prevent Arabidopsis seedling de
      etiolation in darkness.
AB  - In many plants, photomorphogenesis is the default developmental program after
      seed germination, and provides the key features that allow adaptation to light.
      This program is actively repressed if germination occurs in the absence of light,
      through a mechanism dependent on the E3 ubiquitin ligase activity that is encoded
      in Arabidopsis by COP1 (CONSTITUTIVE PHOTOMORPHOGENIC 1), which induces
      proteolytic degradation of transcription factors necessary for light-regulated
      development, such as HY5 (LONG HYPOCOTYL 5) and HYH (LONG HYPOCOTYL 5 HOMOLOG),
      and stabilization of transcription factors that promote skotomorphogenesis, such
      as PIF3 (PHYTOCHROME INTERACTING FACTOR 3). Seedlings deficient in gibberellin
      (GA) synthesis or signaling display a de-etiolated phenotype when grown in
      darkness, equivalent to the phenotype of cop1 mutants, which indicates that the
      switch between photo- and skotomorphogenesis is also under hormonal control. Here
      we provide evidence for the existence of crosstalk between GA and the COP1
      mediated pathway, and identify HY5 and the PIF family as nodes of a regulatory
      network. This interaction occurs through distinct molecular mechanisms, based on
      the observation that GA signaling regulates protein stability of HY5, and the
      activity of PIF3.

PMID- 18053006
TI  - Application of carborundum abrasion for investigating the leaf epidermis:
      molecular cloning of Catharanthus roseus 16-hydroxytabersonine-16-O
      methyltransferase.
AB  - The Madagascar periwinkle (Catharanthus roseus) produces the well-known and
      remarkably complex anti-cancer dimeric alkaloids vinblastine and vincristine that
      are derived from the coupling of vindoline and catharanthine monomers. This study
      describes the novel application of a carborundum abrasion (CA) technique for
      large-scale isolation of leaf epidermis-enriched proteins in order to purify to
      apparent homogeneity 16-hydroxytabersonine-16-O-methyltransferase (16OMT), which
      catalyses the second of six steps in the conversion of tabersonine into
      vindoline, and to clone the gene. Functional expression and biochemical
      characterization of recombinant 16OMT demonstrated its very narrow substrate
      specificity and high affinity for 16-hydroxytabersonine. In addition to allowing
      the cloning of this gene, the CA technique clearly showed that 16OMT is
      predominantly expressed in Catharanthus leaf epidermis. The results provide
      compelling evidence that most of the pathway for vindoline biosynthesis,
      including the O-methylation of 16-hydroxytabersonine, occurs exclusively in the
      leaf epidermis, with subsequent steps occurring in other leaf cell types.

PMID- 18053007
TI  - Effect of short-term exposure to air pollution and pollen on medical emergency
      calls: a case-crossover study in Spain.
AB  - BACKGROUND: A symmetric case-crossover design was used to analyse the short-term
      relationship between air pollution, pollen and emergency calls to medical
      services. METHODS: This study covered patients who made medical emergency calls
      in the City of Vigo (Spain) during the period 1996-1999. Morbidity data were
      obtained from the records of the 061 Medical Emergency Control Center, in its
      capacity as the body officially coordinating all medical emergencies by
      telephone. Air pollution data were furnished by the Vigo Municipal Air Pollution
      Surveillance Grid. Pollen levels were provided by the staff of the Spanish
      Aerobiology Network in Vigo. RESULTS: A rise of 10 microg/m(3) in ambient
      particulate levels led to the risk of medical emergency calls requesting
      attention increasing by: (i) 1.97% [95% confidence interval (95% CI): 1.83-2.11%]
      for circulatory causes on the same day; (ii) 1.95% (95% CI: 1.76-2.14%) for
      respiratory causes at 2 days and (iii) 1.34% (95% CI: 1.23-1.45%) for combined
      circulatory and respiratory causes on the same day. A number of pollens displayed
      a statistically significant relationship with emergency calls. No interaction was
      in evidence between pollens and air pollutants. CONCLUSIONS: While elevations in
      particulate air pollution increase medical emergency calls because of cardiac or
      respiratory causes or both combined, elevations in pollen levels increase medical
      emergency calls because of respiratory causes.

PMID- 18053008
TI  - Prevalence and cumulative incidence of food hypersensitivity in the first 3 years
      of life.
AB  - BACKGROUND: Prevalence and incidence of food hypersensitivity (FHS) and its
      trends in early childhood are unclear. METHODS: A birth cohort born on the Isle
      of Wight (UK) between 2001 and 2002 was followed-up prospectively. Children were
      clinically examined and skin prick tested at set times and invited for food
      challenges when indicated. RESULTS: Nine hundred and sixty-nine children were
      recruited and 92.9%, 88.5% and 91.9% of them respectively were assessed at 1, 2
      and 3 years of age. Prevalence of sensitization to foods was 2.2%, 3.8% and 4.5%
      respectively at these ages. Cumulatively, 5.3% [95% confidence interval (CI): 3.9
      7.1] children were sensitized to a food. Using open food challenge and a good
      clinical history, the cumulative incidence of FHS was 6.0% (58/969, 95% CI: 4.6
      7.7). Based on double-blinded, placebo-controlled, food challenge (DBPCFC) and a
      good clinical history, the cumulative incidence was 5.0% (48/969, 95% CI: 3.7
      6.5). There is no evidence to suggest that the incidence of FHS has increased,
      comparing these results with previous studies. Overall, 33.7% of parents reported
      a food-related problem and of these, 16.1% were diagnosed with FHS by open
      challenge and history and 12.9% by DBPCFC and history. Main foods implicated were
      milk, egg and peanut. CONCLUSIONS: By the age of 3 years, 5-6% of children suffer
      from FHS based on food challenges and a good clinical history. There were large
      discrepancies between reported and diagnosed FHS. Comparing our data with a study
      performed in the USA more than 20 years ago, there were no significant
      differences in the cumulative incidence of FHS.

PMID- 18053009
TI  - SCF and IL-31 rather than IL-17 and BAFF are potential indicators in patients
      with allergic asthma.
AB  - BACKGROUND: Although the prevalence of allergic asthma increased quickly in the
      past decade, the diagnostic criteria have not been well established. The aim of
      the present study was to explore whether stem cell factor (SCF), B cell
      activating factor (BAFF), and cytokines interleukin (IL)-17 and IL-31 are usable
      parameters for the diagnosis of allergic asthmatics. METHODS: Blood samples were
      collected from patients with allergic asthma, control patients, and healthy
      control subjects. The serum concentrations of SCF, BAFF, IL-17, and IL-31 were
      measured by enzyme-linked immunosorbent assay. The corresponding mRNA levels in
      peripheral blood mononuclear cells (PBMCs) were determined by real-time reverse
      transcription polymerase chain reaction. RESULTS: A good correlation existed
      between protein levels of SCF and IL-31 and their mRNA levels (SCF: r = 0.6162;
      IL-31: r = 0.5463). The serum concentrations of SCF and IL-31 in allergic
      asthmatic patients, but not control patients, were significantly higher than
      those in normal control subjects (SCF: median 1.83 vs 0.85 ng/ml, P < 0.01; IL
      31: 50.15 vs 10.01 pg/ml, P < 0.001). Consistently, the levels of SCF and IL-31
      mRNAs in allergic asthmatic patients' PBMCs were also significantly higher than
      those in normal control subjects (P = 0.002 and P < 0.001, respectively).
      CONCLUSIONS: These findings suggest that allergic asthma is characterized by an
      elevation of cytokines SCF and IL-31 and the measurement of their expression at
      either protein level in serum or mRNA level in PBMCs will be a valuable parameter
      for the diagnosis of allergic asthma.

PMID- 18053010
TI  - Evaluation of cytokine mRNA in induced sputum from patients with allergic
      rhinitis: relationship to airway hyperresponsiveness.
AB  - BACKGROUND: Although airway hyperresponsiveness (AHR) is a characteristic feature
      of asthma, it is also frequently present in allergic rhinitis (AR). However, the
      pathogenesis of AHR is unclear and the roles of cytokines in the airway have not
      been well established in AR. We sought to compare cytokine mRNA levels in the
      sputum of AR patients with or without AHR and those of asthma patients, and to
      evaluate whether differences in cytokine levels are associated with the
      development of an abnormal airway response and the absence of respiratory
      symptoms in AR patients with AHR. METHODS: Airway cells were obtained by sputum
      induction from 18 AR patients with AHR, 58 AR patients without AHR, and 27 asthma
      patients. Airway cell cytokine levels, interleukin (IL) -4, IL-5, IL-13, vascular
      endothelial growth factor (VEGF), and interferon-gamma (IFN-gamma), were studied
      at the mRNA level by RT-PCR. RESULTS: Vascular endothelial growth factor and IL-5
      mRNA levels were significantly higher in AR patients with AHR than in AR patients
      without AHR, but these were lower than those of asthmatic patients. Eosinophils
      were significantly higher in AR patients with AHR and in asthmatic patients than
      in AR patients without AHR. Interleukin-4, IL-13, and IFN-gamma levels were not
      elevated in AR patients with or without AHR vs asthma patients. CONCLUSIONS:
      These findings suggest that VEGF and IL-5 can be important determinants of the
      development of AHR in AR patients and that lower levels of other cytokines may be
      associated with the absence of asthmatic symptoms in AR patients with AHR.

PMID- 18053011
TI  - Sinonasal pathology in nonallergic asthma and COPD: 'united airway disease'
      beyond the scope of allergy.
AB  - BACKGROUND: In contrast to the epidemiological and clinical association between
      allergic rhinitis and asthma, upper airway inflammation is less characterized in
      patients with nonatopic asthma and virtually unexplored in chronic obstructive
      pulmonary disease (COPD). Here, sinonasal pathology is studied in patients with
      allergic asthma, nonallergic asthma and COPD. METHODS: Ninety patients with
      stable bronchial disease were included in the study, of which 35 were diagnosed
      with allergic asthma, 24 with nonallergic asthma and 31 with COPD. Concurrently,
      61 control subjects without pulmonary disease were included and matched for age
      and smoking habits respectively with the asthma and the COPD group. Sinonasal
      symptoms were evaluated on a visual analogue scale and rhinosinusitis-related
      impairment of quality of life was assessed with the sino-nasal outcome test-22
      (SNOT-22) questionnaire. Nasal mucosal abnormalities were quantified with nasal
      endoscopy and nasal secretions collected for measuring inflammatory mediators.
      RESULTS: Allergic asthmatics, nonallergic asthmatics and COPD patients reported
      more nasal symptoms than their respective control subjects, had a higher SNOT-22
      score and presented more mucosal abnormalities in the nose. Nasal secretions of
      both allergic and nonallergic asthmatics contained higher levels of eotaxin, G
      CSF, IFN-gamma and MCP-1 than controls. Allergic asthmatics had higher nasal IP
      10 levels as well. COPD-patients had higher nasal levels of eotaxin, G-CSF and
      IFN-gamma than controls. CONCLUSION: Patients with allergic and nonallergic
      asthma and COPD show increased nasal symptoms and more nasal inflammation. Hence,
      our data confirm the 'united airways' concept to be beyond the scope of allergic
      asthma.

PMID- 18053012
TI  - Consensus statements, evidence-based medicine and guidelines in allergic
      diseases.

PMID- 18053013
TI  - Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report.
AB  - Asthma is the leading chronic disease among children in most industrialized
      countries. However, the evidence base on specific aspects of pediatric asthma,
      including therapeutic strategies, is limited and no recent international
      guidelines have focused exclusively on pediatric asthma. As a result, the
      European Academy of Allergy and Clinical Immunology and the American Academy of
      Allergy, Asthma and Immunology nominated expert teams to find a consensus to
      serve as a guideline for clinical practice in Europe as well as in North America.
      This consensus report recommends strategies that include pharmacological
      treatment, allergen and trigger avoidance and asthma education. The report is
      part of the PRACTALL initiative, which is endorsed by both academies.

PMID- 18053014
TI  - Practical allergy (PRACTALL) report: risk assessment in anaphylaxis.
AB  - Effector mechanisms in anaphylaxis were reviewed. Current approaches to
      confirmation of the clinical diagnosis were discussed. Improved methods for
      distinguishing between allergen sensitization (which is common in the general
      population) and clinical risk of anaphylaxis (which is uncommon) were
      deliberated. Innovative techniques that will improve risk assessment in
      anaphylaxis in the future were described.

PMID- 18053015
TI  - Methodology for development of the Allergic Rhinitis and its Impact on Asthma
      guideline 2008 update.
AB  - BACKGROUND: We describe the methodology for the 2008 update of the Allergic
      Rhinitis and its Impact on Asthma (ARIA) guidelines. The methodology differs from
      the 2001 edition in several respects. The most prominent change is the
      application of the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) approach to compiling evidence, assessing the quality of
      evidence and grading of recommendations. METHODS AND RESULTS: Representatives of
      the GRADE working group joined the ARIA guideline panel to achieve these tasks.
      While most recommendations result from existing systematic reviews, systematic
      reviews were not always available and the panel compiled the best available
      evidence in evidence profiles without conducting actual reviews. The panel
      conducted two meetings and used the GRADE criteria to assess the quality of
      evidence (four categories of high, moderate, low and very low) and the strength
      of recommendation (strong and weak) based on weighing up the desirable and
      undesirable effects of management strategies, considering values and preferences
      influencing recommendations, and resource implications. The guideline panel has
      chosen the words 'we recommend'--for strong recommendations and 'we suggest'--for
      weak recommendations. Both categories indicate the best course of action for a
      given patient population, but their implementation, requires different
      considerations as we describe subsequently in this article. CONCLUSIONS: The 2008
      update of the ARIA guidelines has become more evidence-based. Future iterations
      of the guidelines will further be improved by following the described processes
      even closer, such as ensuring availability of updated high quality systematic
      reviews for each question.

PMID- 18053016
TI  - The functional insufficiency of human CD4+CD25 high T-regulatory cells in
      allergic asthma is subjected to TNF-alpha modulation.
AB  - BACKGROUND: Natural CD4(+)CD25(high)Foxp3(+) regulatory T (nTreg) cells are
      important in maintaining immunologic tolerance, but their role in the
      pathogenesis of allergic asthma is unclear. We studied the function of nTreg
      cells in allergic asthmatic children and assessed the factors which may relate to
      the functional insufficiency of nTreg cells. METHODS: The percentage of
      CD4(+)CD25(high) Treg cells, the expression of Foxp3, and the cell-induced
      suppressive activity of nTreg cells isolated from nonatopic controls, allergic
      asthmatics, and allergen-specific immunotherapy (AIT)-treated asthmatic patients
      were studied. RESULTS: Although the percentage of nTreg in peripheral blood
      mononuclear cells was increased, the expression of Foxp3 and its cell-induced
      suppressive activity were significantly lower in Dermatophagoides pteronyssinus
      (Der p)-sensitive asthmatic children when compared to nonatopic controls. In
      contrast, the expression of Foxp3 and the functional activity of nTreg cells were
      reversed in allergic asthmatics who received AIT. The addition of recombinant
      tumor necrosis factor (TNF)-alpha directly downregulated Foxp3 expression and
      abrogated the cell-induced suppressive function of Treg cells. The anti-TNF-alpha
      reagent, etanercept, restored the functional activity and Foxp3 expression of
      CD4(+)CD25(high) Treg derived from allergic asthmatics. CONCLUSIONS: The
      functional insufficiency of nTreg cells in patients with allergic asthma may be
      related to the enhanced production of TNF-alpha and its effect on the Foxp3
      expression. These results may explain, in part, the effectiveness of anti-TNF
      alpha therapy in the treatment of allergic asthma.

PMID- 18053017
TI  - Predictivity of allergic sensitization (RAST) for the onset of allergic diseases
      in adults.
AB  - BACKGROUND: Specific IgE antibodies are often detected without any clinical
      manifestation of allergies. We aimed to analyse the predictivity of allergic
      sensitization for incident symptoms of allergic diseases in adults during a 10
      year follow-up. METHODS: In 1994/95 specific IgE antibodies against five common
      inhalant allergens (grass pollen, birch pollen, house dust mite, cat dander and
      Cladosporium) were diagnosed by radioallergosorbent test in 4178 adults aged 25
      74 years. A subset of 2656 participants could be re-evaluated in 2004/05.
      Information on socio-economic factors and medical history, including data on
      atopic diseases, was assessed by a combination of a personal interview and a self
      administered questionnaire. Logistic regression models were applied to study
      associations between allergic sensitization and incident allergic diseases.
      RESULTS: Allergic sensitization was an important predictor for incident hay fever
      (OR 7.95, CI 95% 4.64-13.62) and asthma (OR 1.82, CI 95% 1.29-2.57). Specific IgE
      antibodies were mainly related to outdoor allergens (grass and birch pollen) for
      hay fever and indoor allergens (mite and cat dander) for asthma, while for atopic
      dermatitis no specific IgE antibodies were identified as major predictors.
      CONCLUSIONS: Allergic sensitization not only covers clinically apparent
      allergies, but indicates a prognostic factor for later allergies, even in
      adulthood.

PMID- 18053018
TI  - Asthma, body mass, gender, and Hispanic national origin among 517 preschool
      children in New York City.
AB  - BACKGROUND: Striking differences in asthma prevalence have been reported among
      Hispanic adults and children living in different cities of the USA. Prevalence is
      highest among those of Puerto Rican and lowest among those of Mexican origin. We
      hypothesized that body size would mediate this association. METHODS: Parents of
      children in New York City Head Start programs completed a questionnaire including
      demographic factors, health history, a detailed history of respiratory
      conditions, lifestyle, and home environment. Children's height and weight were
      measured in home visits. Logistic regression was used to model the association of
      asthma with body mass index percentile (<85th percentile, gender/age specific
      vs>or=85th percentile, gender/age specific), national origin, and other factors.
      RESULTS: Of 517 children at mean age of 4.0 +/- 0.6 years, 34% met the study
      criteria for asthma, and 43% were above the 85th percentile. Asthma was strongly
      associated with non-Mexican national origin, male gender, allergy symptoms, and
      maternal asthma, and marginally with body size. The odds of asthma among boys of
      non-Mexican origin was 5.9 times that among boys of Mexican origin [95%
      confidence interval (CI): 2.9-12.2]; the comparable odds ratio (OR) among girls
      was 1.8 (95% CI: 0.9-3.6). Body mass was associated with asthma among girls [OR =
      2.0 (95% CI: 1.1-3.7)], but not boys [OR = 1.4 (95% CI: 0.8-2.6)]. CONCLUSIONS:
      The association of asthma with both body mass and national origin was gender
      specific among the children in our study. Ours is one of the first studies to
      report on pediatric asthma in different Hispanic populations in the same city, by
      gender.

PMID- 18053019
TI  - Indacaterol provides sustained 24 h bronchodilation on once-daily dosing in
      asthma: a 7-day dose-ranging study.
AB  - BACKGROUND: Indacaterol is a novel, once-daily beta(2)-agonist in development for
      the treatment of asthma and chronic obstructive pulmonary disease. Studies were
      required to determine optimal dose(s) for continuing investigation. OBJECTIVE: A
      dose-ranging study was undertaken to evaluate efficacy and safety of indacaterol.
      METHODS: A total of 436 patients with persistent asthma receiving inhaled
      corticosteroids were randomized to 7 days treatment with once-daily indacaterol
      50, 100, 200, or 400 microg via multi-dose dry-powder inhaler (MDDPI;
      Certihaler), indacaterol 400 microg via single-dose dry-powder inhaler (SDDPI),
      or placebo. Serial 24-h spirometry was performed on days 1 and 7. Vital signs,
      laboratory evaluations, and adverse events were monitored. RESULTS: All doses of
      indacaterol increased the mean time-standardized area under the curve of forced
      expiratory volume in 1 s (FEV(1)) from 22 to 24 h postdose (P <or= 0.001 vs
      placebo) on days 1 and 7, with clinically relevant treatment-placebo differences
      of 240, 260, 350, 300, and 380 ml on day 1 and 230, 220, 320, 250, and 270 ml on
      day 7 for indacaterol 50, 100, 200, and 400 microg via MDDPI and 400 microg via
      SDDPI, respectively. All doses increased mean FEV(1) (P < 0.05 vs placebo) from 5
      min to 24 h postdose on days 1 and 7. All doses were well tolerated. Most adverse
      events were mild-to-moderate in severity: most frequently reported were
      respiratory, thoracic, and mediastinal disorders. CONCLUSION: Once-daily dosing
      with indacaterol provided sustained 24-h bronchodilation in patients with
      moderate-to-severe asthma, with a satisfactory overall safety profile.
      Indacaterol 200 microg appears the optimum dose, offering the best
      efficacy/safety balance.

PMID- 18053020
TI  - Safety of triflusal (antiplatelet drug) in patients with aspirin-exacerbated
      respiratory diseases.
AB  - BACKGROUND AND AIMS: Aspirin, a cyclo-oxygenase (COX)-1 and COX-2 inhibitor, is
      the antiplatelet drug of choice to prevent serious vascular events. Adverse
      reactions to aspirin are frequent particularly among patients with asthma,
      chronic rhinosinusitis and nasal polyps. COX-1 inhibitors but not COX-2
      inhibitors precipitate asthma attacks. Triflusal is a preferential COX-2
      inhibitor antiplatelet agent that is as effective as aspirin in the prevention of
      serious vascular events. The aim of the study was to assess the tolerability of
      triflusal in patients with aspirin-exacerbated respiratory disease (AERD).
      METHODS: We studied 26 asthma patients [11 males, aged 52 (23-75) years] who had
      suffered asthma episodes triggered by one or more (23% of patients) nonsteroidal
      anti-inflammatory drugs. Aspirin sensitivity was confirmed by either intranasal
      or oral aspirin challenge. All subjects underwent a single-blind, placebo
      controlled oral challenge with three doses of triflusal separated by 1 week
      (first cumulative dose = 225 mg; second cumulative dose = 450 mg; third
      cumulative dose = 900 mg). Cutaneous, respiratory, general symptoms and lung
      function were monitored for 4 h in the laboratory and for 24 h at home. RESULTS:
      No clinical reactions to triflusal were observed. There were no significant
      changes in lung function measurements. CONCLUSION: Our study appears to
      demonstrate that triflusal is a suitable alternative to aspirin as antiplatelet
      agent to prevent AERD.

PMID- 18053021
TI  - The socio-economic burden of asthma is substantial in Europe.
AB  - BACKGROUND: Few data are available on the asthma burden in the general
      population. We evaluated the level and the factors associated with the asthma
      burden in Europe. METHODS: In 1999-2002, 1152 adult asthmatics were identified in
      the European Community Respiratory Health Survey (ECRHS)-II and the socio
      economic burden (reduced activity days and hospital services utilization in the
      past 12 months) was assessed. RESULTS: The asthmatics with a light burden (only a
      few reduced activity days) were 13.2% (95% CI: 11.4-15.3%), whereas those with a
      heavy burden (many reduced activity days and/or hospital services utilization)
      were 14.0% (95% CI: 12.1-16.1%). The burden was strongly associated with disease
      severity and a lower quality of life. Obese asthmatics had a significantly
      increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18-4.00]
      or a heavy burden (RRR = 2.77; 95% CI: 1.52-5.05) compared with
      normal/underweight subjects. The asthmatics with frequent respiratory symptoms
      showed a threefold (RRR = 2.74; 95% CI: 1.63-4.61) and sixfold (RRR = 5.76; 95%
      CI: 3.25-10.20) increased risk of a light or a heavy burden compared with
      asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory
      volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence
      with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88;
      95% CI: 1.16-3.06). An interaction was found between gender and IgE
      sensitization, with nonatopic asthmatic females showing the highest risk of a
      heavy burden (21.6%; 95% CI: 16.9-27.1%). CONCLUSIONS: The asthma burden is
      substantial in Europe. A heavy burden is more common in asthmatics with obesity,
      frequent respiratory symptoms, low lung function, chronic cough/phlegm and in
      nonatopic females.

PMID- 18053022
TI  - Role of symptoms and lung function in determining asthma control in smokers with
      asthma.
AB  - BACKGROUND: Cigarette smoking in asthma increases the severity and accelerates
      the decline in lung function. The relative role of symptoms and lung function in
      determining asthma control in smokers with asthma is not known. AIM OF THE STUDY:
      The aim of this study was to compare asthma control in smokers vs never-smokers
      with asthma, using the validated Juniper asthma control questionnaire (ACQ), and
      assess if any difference was because of a particular symptom or the forced
      expiratory volume in one second (FEV(1)) value. METHODS: This was a cross
      sectional study of 134 asthmatics (74 never-smokers and 60 smokers) with >or=15%
      reversibility in FEV(1) after salbutamol. All subjects completed the ACQ,
      recording FEV(1) and asthma symptoms (night awakening, morning symptoms,
      dyspnoea, wheeze, activity limitation and use of reliever inhaler). RESULTS:
      Compared with the never-smokers, smokers with asthma had significantly worse
      median (IQR) total asthma control score [1.6 (1.1-2.3) vs 2.8 (1.7-3.4); (P <
      0.0001)] and in each of the six individual symptom question scores (P < 0.001),
      but no difference in FEV(1) levels (P = 0.908). CONCLUSION: Asthma control is
      significantly worse in asthmatics who smoke compared with never-smokers, with all
      symptoms related to asthma control uniformly worse in smokers, independent of
      FEV(1).

PMID- 18053023
TI  - Author's reply on: 'Obtaining concomitant control of allergic rhinitis and asthma
      with a nasally inhaled steroid'.

PMID- 18053024
TI  - Injection site reactions to TNF-alpha blocking agents with positive skin tests.

PMID- 18053025
TI  - Mast cell activation after adenosine inhalation challenge in patients with
      bronchial asthma.

PMID- 18053026
TI  - The dorsal motor nucleus of the vagus is not an obligatory trigger site of
      Parkinson's disease: a critical analysis of alpha-synuclein staging.
AB  - AIMS: It has been proposed that alpha-synuclein (alpha Syn) pathology in
      Parkinson's disease (PD) spreads in a predictable caudo-rostral way with the
      earliest changes seen in the dorsal motor nucleus of the vagus nerve (DMV).
      However, the reliability of this stereotypical spread of alpha Syn pathology has
      been questioned. In addition, the comparative occurrence of alpha Syn pathology
      in the spinal cord and brain has not been closely studied. METHODS: In order to
      address these issues, we have examined 71 cases of PD from the UK Parkinson's
      Disease Society Tissue Bank at Imperial College, London. The incidence and
      topographic distribution of alpha Syn pathology in several brain regions and the
      spinal cord were assessed. RESULTS: The most affected regions were the substantia
      nigra (SN; in 100% of cases) followed by the Nucleus Basalis of Meynert (NBM) in
      98.5%. Fifty-three per cent of cases showed a distribution pattern of alpha Syn
      compatible with a caudo-rostral spread of alpha Syn through the PD brain.
      However, 47% of the cases did not fit the predicted spread of alpha Syn pathology
      and in 7% the DMV was not affected even though alpha Syn inclusions were found in
      SN and cortical regions. We also observed a high incidence of alpha Syn in the
      spinal cord with concomitant affection of the DMV and in a few cases in the
      absence of DMV involvement. CONCLUSIONS: Our results demonstrate a predominant
      involvement of the SN and NBM in PD but do not support the existence of a
      medullary induction site of alpha Syn pathology in all PD brains.

PMID- 18053027
TI  - Low level of microsatellite instability in paediatric malignant astrocytomas.
AB  - AIM: Microsatellite instability (MSI) has been proposed as a possible mechanism
      in the development of cancer. The aim of the current study was to determine
      whether MSI is involved in the pathogenesis of paediatric malignant astrocytomas.
      METHODS: We screened a cohort of 126 high-grade astrocytoma samples for MSI using
      a sensitive and precise method of DNA analysis including a panel of five
      mononucleotide repeats, in combination with immunohistochemistry for DNA mismatch
      repair (MMR) proteins. RESULTS: We identified low level of MSI (MSI-L) in four of
      126 (3.2%) paediatric malignant astrocytic tumours. To analyse the molecular
      profile associated with MSI-L positive tumours, we performed immunohistochemistry
      for protein expression of hMSH6 and p53 as well as mutational analysis of the K
      ras gene. In MSI-L paediatric malignant astrocytic tumours we detected retained
      nuclear expression of hMSH6 protein and strong nuclear accumulation of p53
      protein indicating possible mutations of TP53. There was no correlation between K
      ras mutational status and frequency of MSI in this patient population.
      CONCLUSION: Our results suggest that the MSI-L phenotype is associated with p53
      accumulation and/or mutations. However, this represents only a small subgroup of
      paediatric gliomas with possible distinct biological features, and the
      deficiencies of DNA MMR genes do not play a main role in the tumourigenesis of
      the majority of paediatric malignant astrocytomas.

PMID- 18053029
TI  - Subacute intoxication of a deltamethrin-based preparation (Butox) 5% EC) in
      monosex Nile tilapia, Oreochromis niloticus L.
AB  - The monosex Nile tilapia, Oreochromis niloticus L., was exposed to subacute
      concentration (1.46 microg/l) of a pyrethroid insecticide, deltamethrin for 28
      consecutive days. Behavioural, clinical, haematological, serum biochemical and
      histopathological consequences were assayed at a regular interval of 7 days. The
      abnormal behavioural responses and toxic symptoms were described. Exposure to
      deltamethrin not only significantly decreased lymphocyte and basophile
      percentages, total leucocytic and total erythrocytic counts, haemoglobin
      percentage and packed cell volume value, but also caused serious effects in the
      form of hypoproteinaemia, hypoalbuminaemia, hypercholesterolaemia, hyperglycaemia
      and significantly increased serum aspartate aminotransferase, alanine
      aminotransferase and alkaline phosphatase activities. Moreover, the
      histopathological results indicated that the haemobiotic organs were affected by
      deltamethrin, primarily liver and gills. Our data suggest that subacute exposure
      to deltamethrin exerts a serious metabolic distress on the fish corresponding to
      the exposure period. In addition, the assayed parameters and histopathological
      findings can be as good biomarkers of pyrethroid ecosystem pollution.

PMID- 18053028
TI  - Spatiotemporal patterns of postsynaptic density (PSD)-95 expression after rat
      spinal cord injury.
AB  - AIMS: Postsynaptic density (PSD)-95 is a scaffolding protein linking the N-methyl
      D-aspartate receptor with neuronal nitric oxide synthase (nNOS), which
      contributes to many physiological and pathological actions. We here investigated
      whether PSD-95 was involved in the secondary response following spinal cord
      injury (SCI). METHODS: Spinal cord contusion (SCC) and spinal cord transection
      (SCT) models at thoracic (T) segment 9 (T(9)) were established in adults rats.
      Real-time polymerase chain reaction, Western blot, immunohistochemistry and
      immunofluorescence were used to detect the temporal profile and spatial
      distribution of PSD-95 after SCI. The association between PSD-95 and nNOS in the
      injured cords was also assessed by coimmmunoprecipation and double
      immunofluorescent staining. RESULTS: The mRNA and protein for PSD-95 expression
      were significantly increased at 2 h or 8 h, and then gradually declined to the
      baseline level, ultimately up-regulated again from 5 days to 7 days for its mRNA
      level and at 7 days or 14 days for its protein level after either SCC or SCT. PSD
      95 immunoreactivity was found in neurones, oligodendrocytes and synaptic puncta
      of spinal cord tissues within 5 mm from the lesion site. Importantly, injury
      induced expression of PSD-95 was colabelled by active caspase-3 (apoptotic
      marker), Tau-1 (the marker for pathological oligodendrocytes) and nNOS.
      CONCLUSIONS: Accompanied by the spatio-temporal changes for PSD-95 expression,
      the association between PSD-95 and nNOS undergoes substantial alteration after
      SCI. These two molecules are likely to form a complex on apoptotic neurones and
      pathological oligodendrocytes, which may in turn be involved in the secondary
      response after SCI.

PMID- 18053030
TI  - The hyaluronic acid push technique for the nasojugal groove.

PMID- 18053031
TI  - Late-onset, recurrent facial nodules associated with injection of poly-L-lactic
      acid.

PMID- 18053032
TI  - Adverse effects of Q-switched laser treatment of tattoos.

PMID- 18053033
TI  - Treatment of hidradenitis suppurativa with a nonablative radiofrequency device.

PMID- 18053034
TI  - Shave and phenolization of periungual fibromas, Koenen's tumors, in a patient
      with tuberous sclerosis.

PMID- 18053035
TI  - A case of animal-type melanoma (or pigmented epithelioid melanocytoma?): an open
      prognosis.

PMID- 18053036
TI  - Primary giant cell tumor of soft tissue mimicking a vascular neoplasm.

PMID- 18053037
TI  - Occurrence of a basal cell carcinoma and dermatofibroma in a smallpox vaccination
      scar.

PMID- 18053038
TI  - Mounting the debulk specimen with the first layer: a time-saver in the Mohs unit.

PMID- 18053039
TI  - A moldable dressing for facial skin grafting: polysiloxane.

PMID- 18053040
TI  - Accurate and anatomic midface filler injection by using cheek implants as an
      injection template.

PMID- 18053041
TI  - The use of a 5-microm filter hub increases foam stability when using the double
      syringe technique.

PMID- 18053045
TI  - Long-term results of nail brace application in diabetic patients with ingrown
      nails.
AB  - BACKGROUND: Ingrown toe nail is a common foot problem; however, there are limited
      data concerning the treatment options for diabetic patients. OBJECTIVE: Because
      of the special attention given to avoidance of infection and ulceration of the
      foot in diabetics, we applied a new, simple nail device as a treatment option
      without any systemic treatment or surgical intervention. METHODS AND MATERIALS:
      We applied braces to 21 diabetic patients with ingrown toe nails. All had severe
      pain, erythema, and edema without suppuration or granulation tissue formation.
      Braces were applied until all the symptoms are cleared. We followed the patients
      for 2 years for the recurrence of symptoms and signs. RESULTS: All patients had
      immediate relief of symptoms once the brace was applied. After the dislocation of
      braces, 15 of 21 patients did not have any recurrences for 2 years. Six patients
      had recurrence of pain and ingrown nail and were willing to use the brace once
      more instead of having any operations. CONCLUSION: Nail brace application is a
      safe, simple, and inexpensive treatment option for diabetic patients with ingrown
      toe nails. Although there may be recurrences, patients are willing to use it for
      a second time as it is simple and pain free.

PMID- 18053046
TI  - Surgical treatment of ingrown toenail without matricectomy.
AB  - BACKGROUND: Partial excision of the nail matrix (matricectomy) is generally
      considered necessary in the surgical treatment of ingrown toenail. Recurrences
      may occur, however, and poor cosmetic results are frequently observed. OBJECTIVE:
      The objective is to present a new surgical procedure for ingrown toenail with
      complete preservation of the nail matrix. METHODS: Twenty-three patients with
      ingrown toenail were included in this study. The surgical excision was performed
      1 week after the completion of treatment of the initial infection. A large volume
      of soft tissue surrounding the nail plate was removed under local anesthesia. No
      matrix excision was performed. RESULTS: Short-term results were excellent. No
      recurrences or severe complications were observed during the minimum 12-months
      follow-up period. Cosmetic results were remarkable. CONCLUSIONS: Ingrown toenail
      results from the compression of the lateral nail folds on the nail plate. This
      study shows that ingrown toenail can be surgically treated without matricectomy.
      A large volume of soft tissue surrounding the nail plate should be removed to
      decompress the nail and reduce inflammation. Cosmetic results are excellent and
      superior to the classical Emmert plasty. Postoperative nail dystrophies and
      spicule formation are not observed. The main advantage of this surgical approach
      is the complete preservation of the anatomy and function of the nail to improve
      both therapeutic and cosmetic results.

PMID- 18053047
TI  - Fractional photothermolysis for photoaging of hands.
AB  - BACKGROUND: Laser treatment for photoaging of the hands should ideally address
      pigmentary alteration as well as associated skin roughness and wrinkling.
      Fractional resurfacing has been previously shown to effectively treat facial
      rhytids and dyschromia. OBJECTIVE: We examined the effect of fractional
      resurfacing for photoaging of the hands. METHODS AND MATERIALS: Ten patients
      (skin phototypes II to IV) with hand photodamage were randomized to receive five
      treatments with a 1,550-nm diode-pumped erbium fiber laser (Fraxel SR, Reliant
      Technologies) laser on either the right or left hand. Treatments were performed
      at settings of 8 to 9 mJ/microscopic treatment zone and density of 2,500
      microscopic treatment zones/cm2. Subjective assessments by the patients and
      investigator were performed for skin roughness, wrinkling, and pigmentation using
      a 5-point scale. Skin biopsies were taken at baseline and at 1 and 3 months.
      RESULTS: Patient subjective assessment and physician clinical assessment at 1 and
      3 months revealed a mean 51% to 75% improvement in skin pigmentation and 25% to
      50% improvement in skin roughness and wrinkling. Biopsies of the skin showed
      increased density of dermal collagen. Patients experienced transient erythema and
      edema and none had scarring or other adverse effects. LIMITATIONS: This was a
      small study. CONCLUSION: Fractional resurfacing appears to be an effective and
      safe treatment modality for correcting both the pigmentary and the textural
      aspects of photoaging of the hand.

PMID- 18053048
TI  - Pulsed dye laser treatment is effective in the treatment of recalcitrant viral
      warts.
AB  - BACKGROUND: Verrucae vulgaris can be removed in a variety of ways but a specific
      therapy of choice has not yet been developed. Doctors are faced with a challenge,
      especially in the treatment of recalcitrant warts. It has been suggested that the
      success of pulsed dye laser treatment lies in the fact that warts contain an
      increased number of dilated blood vessels. METHODS: Seventy-three patients (42
      female, 31 male) with verrucae vulgaris on their hands or feet (1:1.5) were given
      a maximum of 12 treatments with a flashlamp-pumped pulsed dye laser every 2 weeks
      over a period of 24 weeks until complete clearance had been achieved. A laser
      energy density of 8 to 12 J/cm2 with a spot size of 5 mm and a pulse duration of
      450 microsec were used. The minimum follow-up period was 6 months. RESULTS: A
      total of 15.1% patients achieved complete clearance after 1 session and 47.9%
      after 2 to 5 sessions, resulting in a remission of 63.0% patients after a maximum
      of 5 treatment sessions. A remission of 23.3% patients was seen after 6 to 9
      treatments and a total of 89.0% of patients showed remission after a maximum of
      10 sessions. Only three patients (4.1%) failed and five patients (6.9%) stopped
      the treatment on account of pain/noncompliance. Only one patient, from a group of
      patients treated between January 2003 and April 2004, has relapsed. CONCLUSION:
      Pulsed dye laser treatment is effective and safe in the treatment of recalcitrant
      viral warts.

PMID- 18053049
TI  - Phosphatidylcholine and sodium deoxycholate in the treatment of localized fat: a
      double-blind, randomized study.
AB  - BACKGROUND: Recent articles have introduced the novel concept of chemical
      lipolysis through local injections. Phosphatidylcholine is the active drug in the
      commercial preparation used for this purpose, but some studies have suggested
      that sodium deoxycholate, an excipient of the preparation, could be the real
      active substance. AIM: We decided to investigate whether phosphatidylcholine and
      sodium deoxycholate have any clinical efficacy in chemical lipolysis and their
      respective roles. We also studied the safety and side effects of the treatments.
      MATERIALS AND METHODS: Thirty-seven consecutive female patients were studied for
      the treatment of localized fat in gynoid lipodystrophy. Each patient received
      injections of a phosphatidylcholine/sodium deoxycholate preparation on one side
      and sodium deoxycholate on the contralateral side, each single patient being
      herself the control. Four treatments were carried out every 8 weeks in a double
      blind, randomized fashion. Metric circumferential evaluations and photographic
      and ultrasonographic measurements throughout the study allowed for final
      judgment. A statistical evaluation concluded our study. RESULTS: An overall
      reduction of local fat was obtained in 91.9% of the patients without
      statistically significant differences between the treated sides. Reduction values
      on the phosphatidylcholine/sodium deoxycholate-treated sides are in the order of
      6.46% metrically and 36.87% ultrasonographically, whereas on the deoxycholate
      treated sides they are in the order of 6.77% metrically and 36.06%
      ultrasonographically. Both treatments, at the dose used in the study, proved safe
      in the short term. The most common side effects were local and few, but were more
      pronounced on the deoxycholate-treated sides. No laboratory test was carried out.
      CONCLUSION: Both treatments have shown moderate and equivalent efficacy in
      treating localized fat, with sodium deoxycholate having a slower postoperative
      resolution, suggesting that sodium deoxycholate could be sufficient by itself to
      determine fat cell destruction and that phosphatidylcholine could be useful for
      obtaining a later emulsification of the fat.

PMID- 18053050
TI  - A randomized pilot study comparing the action halos of two commercial
      preparations of botulinum toxin type A.
AB  - BACKGROUND: The determination of the action halos of botulinum toxin type A aids
      in targeting specific muscles and/or sweat glands, thereby preventing the
      occurrence of side effects. OBJECTIVES: The objective of this study was to
      compare the action halos of two commercial preparations of botulinum toxin type
      A, Dysport (Ipsen, Slough, UK) and BOTOX (Allergan, Irvine, CA). MATERIAL AND
      METHODS: Eighteen volunteers received applications of both products into
      randomized sides of the frontalis muscle. Equivalent doses of 5 U of Dysport and
      2 U of BOTOX were injected using the same technique, in the same volume (0.02
      mL), and at a controlled depth. Twenty-eight days later, clinical and
      photographic assessments were performed. RESULTS: All the areas around the
      injected points were regular, round, or slightly oval and showed similar effects
      in the muscles and sweat glands. No statistically significant differences were
      observed between the mean sizes of the diameters of the halos produced by the two
      products. CONCLUSION: Injections of Dysport and BOTOX at an equivalence ratio of
      2.5:1 U, respectively, applied at the same volume and depth, using the same
      technique resulted in similar action halos with regard to muscular and sweat
      gland activity. Both products seem to be safe and very predictable.

PMID- 18053051
TI  - Comparison of alpha- and beta-hydroxy acid chemical peels in the treatment of
      mild to moderately severe facial acne vulgaris.
AB  - BACKGROUND: Chemical peels are used as adjuvants for treatment of facial acne. No
      well-controlled studies have compared alpha- and beta-hydroxy acid peels in the
      treatment of mild to moderately severe facial acne. OBJECTIVE: To compare the
      efficacy of alpha- and beta-hydroxy acid chemical peels in the treatment of mild
      to moderately severe facial acne vulgaris. MATERIALS AND METHODS: Twenty patients
      were recruited in this split-face, double-blind, randomized, controlled study. An
      alpha-hydroxy acid (30% glycolic acid) was applied to one-half of the face and a
      beta-hydroxy acid peel (30% salicylic acid) was applied contralaterally every 2
      weeks for a total of six treatments. A blinded evaluator performed quantitative
      assessment of papules and pustules. RESULTS: Both chemical peels were
      significantly effective by the second treatment (p<.05) and there were no
      significant differences in effectiveness between the two peels. At 2 months
      posttreatment, the salicylic acid peel had sustained effectiveness. More adverse
      events were reported with the glycolic acid peel after the initial treatment.
      CONCLUSION: The glycolic acid and salicylic acid peels were similarly effective.
      The salicylic acid peel had sustained effectiveness and fewer side effects. Alpha
      and beta-hydroxy acid peels both offer successful adjunctive treatment of facial
      acne vulgaris.

PMID- 18053052
TI  - Tie-over dressings in full-thickness skin grafts.
AB  - BACKGROUND: A full-thickness skin graft is often performed by tie-over dressing
      to compress and immobilize it. OBJECTIVE: The aim of this study was to compare
      the results of a full-thickness skin graft with tie-over dressing performed with
      the classic technique and with simple dressing. METHODS AND MATERIALS: This was a
      prospective study in which 25 patients had tulle gras jelly tie-over dressing and
      25 patients had a simple tulle gras dressing after full-thickness skin graft for
      nipple areola reconstruction. RESULTS: Graft success on the fifth day was
      evaluated at 100% for patients with a simple dressing and at 99% for those with
      tie-over dressing. CONCLUSIONS: In this study, simple dressing appeared to be at
      least as effective as the tie-over dressing. Simple dressing, however, was faster
      and left fewer residual marks than the tie-over dressing.

PMID- 18053053
TI  - The evaluation of relevant factors influencing skin graft changes in color over
      time.
AB  - BACKGROUND: Objective studies evaluating the relevant factors that affect skin
      graft changes in color over time have yet to be published. OBJECTIVE: Therefore,
      the patterns of the grafted skin's color changes and the presence of relevant
      factors were analyzed statistically. MATERIALS AND METHODS: The study included
      107 skin grafts in 107 subjects. Using a chromameter, the colors of skin graft,
      the area adjacent to the recipient site, and the donor site were measured. The
      grafted skin's color changes and the color difference were analyzed with respect
      to several factors. RESULTS: Over time, the grafted skin became lighter, redness
      decreased, yellowness increased, and the color difference decreased. As the donor
      site was lighter, the grafted skin was lighter and less red. The grafted skin was
      lighter in females than in males. The skin graft type was not related to the
      lightness and the redness. The grafted skin was lightest in the upper arm and
      darkest in the lower leg. The grafted skin was lighter in Fitzpatrick Skin Type
      III, followed by Type IV and then Type V. CONCLUSION: The factors that affected
      the skin graft's lightness were time, the lightness of the donor, sex, the hand,
      the foot, and Fitzpatrick skin type.

PMID- 18053054
TI  - Is levofloxacin necessary to prevent postoperative infections of auricular second
      intention wounds?
AB  - BACKGROUND: Surgeons may prescribe oral quinolones after auricular procedures to
      prevent postoperative infections, especially those caused by Pseudomonas
      aeruginosa. OBJECTIVE: This study compares the efficacy of levofloxacin and local
      wound care to local wound care alone in preventing postoperative infection of
      auricular second-intention wounds. MATERIALS AND METHODS: This study was a
      prospective, randomized trial of 84 consecutive patients (82 in the final
      analysis) who underwent Mohs micrographic surgery for an auricular neoplasm and
      had a wound left to heal by second intention. After surgery, patients were
      randomly assigned to receive either local wound care or local wound care with
      concurrent 500 mg of levofloxacin by mouth daily. RESULTS: Overall, 85.4% of
      patients had no complications. Complications included 12.2% of patients with
      inflammatory chondritis and 2.4% of patients with infection. No infections with
      P. aeruginosa were observed. No statistical significance was observed between the
      two treatment groups. CONCLUSION: Levofloxacin is not necessary to prevent
      postoperative infections of auricular second-intention wounds after Mohs surgery.

PMID- 18053055
TI  - Rapid preparation of high-quality frozen sections using a membrane and vacuum
      system embedding machine.
AB  - BACKGROUND: A wide variety of embedding techniques have been employed to process
      frozen sections for Mohs micrographic surgery. Prospective data comparing
      different techniques are lacking. OBJECTIVE: The purpose of this study was to
      compare tissue processing times and slide quality using the three embedding
      techniques. METHODS: Seventy-five consecutive Mohs surgery tissue specimens,
      measuring 1 cm in diameter, were prospectively randomized to processing with the
      CryoHist, the Cryocup, or the Miami Special. Tissue preparation times were
      recorded, and slide quality was evaluated. Tissue specimen preparation was
      standardized to exclude the use of relaxing incisions or other tissue
      manipulations. In a separate evaluation, slide quality was retrospectively
      evaluated for 50 large specimens (>2.5 cm) processed with the CryoHist machine.
      RESULTS: The mean tissue processing time was 11.4 minutes using the CryoHist,
      12.9 minutes using the Cryocup, and 12.6 minutes using the Miami Special. Slide
      quality, using epidermal edge as a primary end point, was superior with the
      CryoHist compared to the other methods. For large (>2.5 cm) en bloc Mohs
      specimens processed using the CryoHist, the slide quality was excellent with
      92.3% of epidermal edge obtained. CONCLUSIONS: The fully automated CryoHist
      embedding machine enables high-quality frozen sections to be processed in less
      time than the Cryocup or the Miami Special. Slide quality is excellent, even for
      larger specimens.

PMID- 18053056
TI  - Longitudinal diminution of tumor size for basal cell carcinoma suggests shifting
      referral patterns for Mohs surgery.
AB  - BACKGROUND: The Mohs technique for removal of cutaneous malignancies offers
      tissue-sparing benefits compared with other treatment methods. With wider
      acceptance and availability of Mohs surgery, referral patterns may be shifting
      toward the treatment of smaller, lower-risk tumors. OBJECTIVE: The objective was
      to examine whether referral patterns for basal cell carcinoma (BCC) at an
      academic Mohs surgery practice have shifted over recent years toward referral for
      smaller, lower risk tumors. METHODS: A retrospective longitudinal comparison of
      tumor characteristics was performed for BCCs treated at our institution from a
      recent year (2004) and a past year (1996). Statistical analyses were used to
      identify differences in tumor size, distribution by anatomic site, and primary
      versus recurrent status. RESULTS: Complete data were available for 603 BCCs
      treated in 1996 and 1,514 BCCs treated in 2004. A 24% decrease in preoperative
      tumor surface area was observed from 1996 (1.25 cm2) to 2004 (0.95 cm2). Tumors
      were twice as likely to be recurrent in 1996 (15.1%) than in 2004 (7.4%). There
      were no significant differences in the anatomic distribution of lesions in the
      years compared. CONCLUSIONS: Findings at our institution suggest that in recent
      years, referral patterns have shifted toward a preference for Mohs surgery for
      the treatment of smaller, primary BCCs. This may be a result of increased
      awareness by the dermatologic and medical community of the numerous advantages of
      Mohs surgery and a greater appreciation of its tissue-sparing properties, which
      may result in less complex and more successful aesthetic reconstructions.

PMID- 18053057
TI  - Infiltrative basal cell carcinomas presenting as actinic keratosis: implications
      for clinical practice.

PMID- 18053058
TI  - What specialties perform the most common outpatient cosmetic procedures in the
      United States?
AB  - BACKGROUND: The number of cosmetic procedures performed annually is on the rise
      and is being performed by more specialties. PURPOSE: We sought to determine the
      relative outpatient cosmetic procedure experience of dermatology and other
      specialties. We also examined demographic data of patients who underwent cosmetic
      procedures. METHODS: Demographics and data from the National Ambulatory Medical
      Care Survey (NAMCS) were analyzed to estimate the number of visits for office
      based cosmetic procedures from 1995 to 2003 by specialty and type of procedure.
      RESULTS: In order of decreasing frequency, the percentage of all cosmetic
      procedures performed in the outpatient setting by specialty was as follows:
      dermatology (48%), plastic surgery (38%), general surgery (>4%), otolaryngology
      (>3%), ophthalmology (>3%), facial plastic surgery (1%), family practice (<1%),
      pediatrics (<1%), and internal medicine (<1%). Most cosmetic procedures were
      performed on white, female patients in the 40- to 59-year-old age group. There
      was a mean of 55 visits per 1,000 whites and 27 visits per 1,000 nonwhites.
      Chemical peels and soft tissue fillers were the two most common procedures.
      CONCLUSIONS: Dermatology as a specialty performs more office-based cosmetic
      procedures than other specialties. On a per-physician basis, dermatologists and
      plastic surgeons have far more experience with cosmetic procedures than other
      physicians.

PMID- 18053059
TI  - Quality of master impressions and related materials for fabrication of complete
      dentures in the UK.
AB  - The aim of this study was to examine the quality of master impressions and
      related materials for fabricating complete dentures in the UK. One hundred and
      fifty pre-piloted questionnaires were distributed to a number of dental
      laboratories in the UK with large catchment areas. Information requested related
      to the quality and choice of techniques for the master impression stage of
      fabricating complete dentures, as well as prescription of materials for occlusal
      registration, amongst others. All information was recorded anonymously. One
      hundred and forty-four completed questionnaires were returned. All items were
      provided on a private basis. Eighty-three per cent (n=119) of master impressions
      were made using a custom tray, the remainder were made using a plastic stock
      tray. The most commonly used impression material was zinc oxide-eugenol (42%,
      n=60), followed by polyvinylsiloxane (39%, n=56) and irreversible hydrocolloid
      (19%, n=28). Master casts were poured after a minimum of 4 days. Eleven per cent
      of impressions examined (n=16) were judged to have errors. It was reported that
      64% of master impressions (n=92) examined had been disinfected adequately. While
      this study revealed evidence of good clinical practice, particularly in relation
      to the selection of impression trays and quality of master impressions for
      complete dentures, there were some areas of concern, particularly in relation to
      the disinfection of the impressions examined. Dental practitioners should aim to
      provide their patients with high-quality prostheses by observing best clinical
      practice at all times.

PMID- 18053060
TI  - Automatic regulation of occlusal force because of hardness-change of the bite
      object.
AB  - It is considered that the information of chewed food, such as size and texture,
      is important for smooth mastication. In this study, we analysed aspects of the
      control of occlusal force, by experimentally reproducing situations in which the
      hardness of food changed unpredictably during mastication, using a device that
      utilized a 3-sectioned urethane rubber piece with different hardness values.
      Seven healthy subjects were instructed to perform repetitive jaw open-close
      movements paced by a metronome (1.0 Hz) and to maintain constant occlusal force
      throughout the trial. Using the device, the following parameters were measured
      during the first to fifth strokes after changing the hardness, peak value,
      impulse, duration and time to peak of occlusal force in the waveform of occlusal
      force, cycle time of open-close jaw movements, jaw gape and maximum speed in the
      closing phase in the waveform of the jaw movements. Each parameter value was
      statistically analysed by anova with Fisher's least significant difference method
      (P < 0.05). Peak occlusal force, impulse and jaw gape were significantly affected
      by the change in hardness, while an increase in hardness caused increases in the
      values for peak occlusal force and impulse against the instruction, after which
      those values remained constant while the subjects occluded the same level of
      hardness. Our results indicate that the level of the resulting occlusal force is
      regulated automatically according to the hardness of the chewed food. We
      concluded that occlusal force was adapted for efficient mastication when the
      hardness of foods changes unpredictably.

PMID- 18053061
TI  - Zero tolerance of abuse of people with intellectual disabilities: implications
      for nursing.
AB  - AIMS: This paper explores the concept of 'zero tolerance' to abuse in the context
      of the professional responsibilities of all nurses. The workability of zero
      tolerance will be considered in light of findings of a study into abuse.
      BACKGROUND: Registered nurses are led to believe that zero tolerance of abuse of
      patients is the only philosophy consistent with protecting the public. However,
      the approach of zero tolerance is not without its difficulties. Staff,
      particularly registered nurses, who come into contact with people with
      intellectual disabilities have a professional responsibility to prevent and
      report all forms of abuse. DESIGN: This study used a multiphase, multimethod
      approach (literature review, survey and focus groups). METHODS: The results
      reported here relate to the focus group stage of the study. There were 70
      participants in the focus group who worked either as direct care staff with
      people with intellectual disabilities or as investigators of abuse. RESULTS:
      Analysis of recurrent themes indicated that both individual (e.g. a positive
      value base) and systemic factors (e.g. environment) seemed to have an impact on
      how staff will respond to abuse. CONCLUSIONS: This study found that a 'hierarchy
      of abuse' existed among staff who worked with people with intellectual
      disabilities. Individual staff members seemed to be 'weighing up' what they
      perceived as serious abuse before reporting areas of concern. This is in contrast
      to a philosophy of zero tolerance which registered nurses have to adhere to.
      RELEVANCE TO CLINICAL PRACTICE: There needs to be a consistent approach to abuse
      and nurses need to have appropriate training in which to gain confidence in their
      role in preventing, identifying and responding to abuse of patients or clients.

PMID- 18053062
TI  - The emerging role of epidermal growth factor receptor inhibitors in ovarian
      cancer.
AB  - Epidermal growth factor receptor (EGFR) inhibitors are a new biologically
      targeted therapy, which may offer new hope in the treatment of patients with
      advanced or recurrent ovarian cancers. In this review, we summarize and discuss
      the results of research to date on EGFR inhibitors with particular emphasis on
      ovarian cancer. We reviewed data identified by searches of MEDLINE, PubMed, and
      abstracts from the proceedings of the American Society of Clinical Oncology
      meetings from 1998 to 2006, with the search terms "Ovarian
      Cancer,""EGFR,""gefitinib, ZD1839, Iressa,""erlotinib, OSI-774, Tarceva,""CI
      1033,"" GW 572016, lapatinib,""PKI-166,""EKB 569,""anti-EGFR
      antibodies,""trastuzumab, Herceptin,""cetuximab, Erbitux, IMC-C225,""matuzumab,
      EMD 72000,""panitumamab, ABX-EGF,""pertuzumab," and "vandetanib, rINN, Zactima,
      ZD6474." Phase II trials of both small molecule inhibitors of EGFR- and antibody
      based inhibitors are currently ongoing in ovarian cancer and emerging data
      suggest that their activity in unselected women with advanced or recurrent
      ovarian cancer is modest, when utilized as a single agent. It is possible that
      these agents will be highly effective in smaller subsets of patients whose tumors
      are dependent on EGFR signaling, perhaps through activating mutations in EGFR or
      its downstream pathway. Targeted therapy with EGFR inhibitors is an untapped
      potential resource in the treatment of advanced or recurrent ovarian cancer.
      Ongoing trials will elucidate the most effective strategies to use these agents
      individually or in combination with traditional chemotherapeutic agents.

PMID- 18053063
TI  - Extended pelvic resections for recurrent uterine and cervical cancer: out-of-the
      box surgery.
AB  - Patients with recurrent uterine and cervical cancer have poor prognoses. The
      objective of this study was to analyze the outcomes of patients with recurrent
      uterine and cervical cancer who had undergone attempted curative resection of
      pelvic bone, sidewall muscle, major blood vessels, and/or nerves. We reviewed the
      records of all 14 patients with recurrent uterine and cervical cancer who had
      extended pelvic resections at our institution between June 2000 and November
      2006. Primary sites of disease were the uterus (11 patients) and cervix (3
      patients). Tumor histology was as follows: adenocarcinoma, seven; squamous cell
      carcinoma, three; leiomyosarcoma, three; and adenosarcoma, one. Previous
      treatment included hysterectomy, 11; pelvic radiation, 9; chemotherapy, 9; and
      total pelvic exenteration, 2. Extended pelvic resections included removal of
      pelvic sidewall muscle, five; bone, five; common and/or external iliac vessel,
      five; femoral nerve, two; lumbosacral nerve root, one; and obturator nerve, one.
      Other procedures included total pelvic exenteration, three; posterior
      exenteration, two; and anterior exenteration, one. Complete resection with
      negative margins was obtained in 11 (78%) of 14 patients. Seven patients (50%)
      received high-dose rate intraoperative radiation therapy. Reconstructive
      procedures included continent or incontinent urinary diversion, four; femoral
      femoral arterial bypass, two; myocutaneous flap, two; and urinary ileal
      interposition, one. Median total operating time was 628 min (range, 345-935 min)
      and median estimated blood loss was 900 mL (range, 300-16,000 mL). Seven patients
      (50%) had one or more major complication(s), including pelvic abscess, three;
      colonic fistula, two; massive intraoperative hemorrhage, one; postoperative
      bladder perforation, one; thrombosed femoral-femoral graft, one; and disruption
      of appendicocutaneous urinary anastomosis, one. At a median follow-up of 26
      months (range, 5-84 months), ten patients (71%) are alive and four patients (29%)
      have died of disease at 8, 13, 33, and 42 months postoperatively.

PMID- 18053064
TI  - Presence in Legionella pneumophila of a mammalian-like mitochondrial permeability
      transition pore?
AB  - The genome of Legionella pneumophila reveals the presence of a large number of
      genes coding for eukaryotic-like proteins. By using database searches and
      homology investigations, we identified three proteins in L. pneumophila whose
      sequences share similarities with that of eukaryotic polypeptides (lpg0211,
      lpg1974 and lpg1982). In eukaryotes, the corresponding proteins (PBR, peripheral
      benzodiazepine receptor; VDAC, voltage-dependant anion channel; and CypD,
      cyclophilin D) participate in the formation of the mammalian mitochondrial
      permeability transition pore (MPTP), a complex involved in cell apoptosis.
      Intriguingly, the presence of these proteins has never been reported in the same
      bacterium and constitutes, up to now, a unique feature of L. pneumophila. In
      Legionella, we hypothesize that these proteins are recruited in a multiprotein
      complex close to the MPTP that may regulate intracellular survival and/or
      proliferation.

PMID- 18053065
TI  - FT-IR microspectroscopy: a promising method for the rapid identification of
      Listeria species.
AB  - This work presents a pilot study to investigate the potential of fourier
      transform infrared (FT-IR) microspectroscopy for rapid identification of Listeria
      at the species level. Using this technique, FT-IR spectra were acquired from 30
      strains from five Listeria species. The FT-IR spectra were analysed using
      stepwise canonical discriminant analysis and partial least-squares regression in
      a stepwise identification scheme. The results showed that 93% of all the samples
      were assigned to the correct species, and that 80% of the Listeria monocytogenes
      strains were correctly identified. In comparison, 100% of the samples, including
      the L. monocytogenes samples, were correctly identified using spectra acquired by
      FT-IR macrospectroscopy. The results show that FT-IR microspectroscopy has
      potential as a rapid screening method for Listeria, which is especially valuable
      for the food industry.

PMID- 18053066
TI  - A high prevalence of antimicrobial resistant Escherichia coli isolated from pigs
      and a low prevalence of antimicrobial resistant E. coli from cattle and sheep in
      Great Britain at slaughter.
AB  - The incidence of antimicrobial resistance and expressed and unexpressed
      resistance genes among commensal Escherichia coli isolated from healthy farm
      animals at slaughter in Great Britain was investigated. The prevalence of
      antimicrobial resistance among the isolates varied according to the animal
      species; of 836 isolates from cattle tested only 5.7% were resistant to one or
      more antimicrobials, while only 3.0% of 836 isolates from sheep were resistant to
      one or more agents. However, 92.1% of 2480 isolates from pigs were resistant to
      at least one antimicrobial. Among isolates from pigs, resistance to some
      antimicrobials such as tetracycline (78.7%), sulphonamide (66.9%) and
      streptomycin (37.5%) was found to be common, but relatively rare to other agents
      such as amikacin (0.1%), ceftazidime (0.1%) and coamoxiclav (0.2%). The isolates
      had a diverse range of resistance gene profiles, with tet(B), sul2 and strAB
      identified most frequently. Seven out of 615 isolates investigated carried
      unexpressed resistance genes. One trimethoprim-susceptible isolate carried a
      complete dfrA17 gene but lacked a promoter for it. However, in the remaining six
      streptomycin-susceptible isolates, one of which carried strAB while the others
      carried aadA, no mutations or deletions in gene or promoter sequences were
      identified to account for susceptibility. The data indicate that antimicrobial
      resistance in E. coli of animal origin is due to a broad range of acquired genes.

PMID- 18053067
TI  - The ability to utilize mucin affects the regulation of virulence gene expression
      in Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae colonizes the mucin-rich environment of the nasopharynx.
      As colonization may be the first stage of infection, investigation was carried
      out as to whether the pneumococcus could utilize mucin as a source of nutrient
      and whether its virulence gene expression is influenced by this glycoprotein. It
      was found that when grown in Sicard's defined medium supplemented with 1% w/v
      mucin, the organism grew at a rate similar to that in rich medium. The presence
      of sialate O-acetylesterase activity, an enzyme implicated in glycoprotein
      degradation, in pneumococcal cell extracts was also reported. The authors
      hypothesized that neuraminidase A, which is linked to pneumococcal virulence,
      plays an important role in mucin utilization. Growth in mucin resulted in an
      increase in nanA transcription and a DeltananA-deficient strain of pneumococcus
      could not grow when mucin was used as the sole carbon source.

PMID- 18053068
TI  - Determination of how many immunoglobulin variable region heavy chain mutations
      are allowable in unmutated chronic lymphocytic leukaemia - long-term follow up of
      patients with different percentages of mutations.
AB  - The choice of 98% sequence homology for immunoglobulin heavy chains to
      distinguish between mutated and unmutated versions of chronic lymphocytic
      leukaemia (CLL) was arbitrary and was chosen to account for supposed
      polymorphisms. Some authors chose 97% or even 95%. This study examined survival
      curves for cohorts of patients with varying degrees of sequence homology. All
      patients with <97% homology behaved as if mutated. Those with 97-98% homology
      were more aggressive than the mutated cases, but less aggressive than those with
      >98% homology.

PMID- 18053069
TI  - Gloves and socks syndrome after bone marrow transplantation.

PMID- 18053070
TI  - PI3K/AKT pathway activation in acute myeloid leukaemias is not associated with
      AKT1 pleckstrin homology domain mutation.
AB  - Despite its' central role, the precise mechanisms of the phosphoinositide 3
      kinase/Akt (PI3K)/Akt pathway activation in acute myeloid leukaemia (AML) have
      not been elucidated. Recently, a recurrent novel AKT1 pleckstrin homology domain
      (PHD) mutation leading to membrane translocation, constitutive AKT activation and
      leukaemia development in mice was described. To assess AKT1 PHD mutations in AML,
      we sequenced 57 specimens from 49 AML patients, all of whom showed PI3K/AKT
      pathway activation by analysis of total and phospho-protein expression for AKT,
      mTor, p70S6Kinase, S6ribosomal protein and PTEN. No mutations in AKT1 PHD were
      identified, making this mutation an unlikely cause of PI3K/AKT pathway activation
      in AML.

PMID- 18053071
TI  - Intentional induction of mixed haematopoietic chimerism as platform for cellular
      therapy after HLA-matched allogeneic stem cell transplantation in childhood
      leukaemia patients.
AB  - Allogeneic peripheral blood stem cell CD34(+)-selected transplantation followed
      by donor lymphocyte infusion (DLI) to maximize graft-versus-leukaemia effect
      while avoiding graft-versus-host disease was investigated in 22 paediatric
      patients with acute myeloid leukaemia (n = 10) or acute lymphoblastic leukaemia
      (n = 12). Patients were grafted with a median (range) 6 x 10(6) (2-31 x 10(6))/kg
      CD34(+) cells and 1.1 x 10(4) (0.2-3.9 x 10(4)) CD3(+) cells. Seventy-five DLI
      were performed with no complications. Median time (range) to neutrophil and
      platelet engraftment was 13 (11-15) and 12 d (8-13) respectively. Probability of
      relapse and disease-free survival was 23 +/- 9% and 72 +/- 6% respectively
      (median follow-up of 15 months).

PMID- 18053072
TI  - Extraordinary AFLP fingerprint similarity despite strong assortative mating
      between reef fish color morphospecies.
AB  - Recent theoretical models and empirical studies of fruit flies, birds, and fish
      indicate that assortative mating may initiate speciation when physical barriers
      to gene flow are absent, and before postzygotic barriers evolve. These are
      important results for marine animals like coral reef fish, where ocean currents
      can carry planktonic larvae over broad ranges, interconnecting populations and
      slowing genetic divergence. The Caribbean hamlets (genus Hypoplectrus) are a
      flock of reef fish morphospecies with highly distinct color pattern that mate
      like with like, but show little mitochondrial or microsatellite DNA
      differentiation. Here, we broadly screen genomic diversity using amplified
      fragment length polymorphisms (AFLP) and survey mating pair formation between two
      morphospecies in the Florida Keys, the butter hamlet (H. unicolor) and the blue
      hamlet (H. gemma). No AFLP was species-diagnostic (fixed), and neighbor-joining
      analyses revealed no clustering of individuals consistent with morphospecies
      boundaries. Assignment tests, however, placed most individuals within their
      morphospecies of origin. Field surveys showed that > 98% of mating pairs,
      including those of rare morphospecies, were of like color pattern. Spawning by a
      single mixed pair adds to earlier observations suggesting that infrequent
      hybridization may be a genetically homogenizing force in Hypoplectrus. This study
      provides a clear example of strong assortative mating in a system with limited
      genetic differentiation.

PMID- 18053073
TI  - Multiple genetic benefits of female promiscuity in a socially monogamous
      passerine.
AB  - The adaptive function of female extrapair mating in socially monogamous
      passerines is currently debated. In the bluethroat (Luscinia s. svecica), a
      previous study showed that offspring sired by extrapair males had a higher cell
      mediated immunity than their within-pair half siblings, suggesting an
      immunogenetic benefit of extrapair mating in this species. Here, we expanded that
      dataset with two more years and investigated the association between extrapair
      paternity and microsatellite multilocus heterozygosity, in addition to cell
      mediated immunity. We found that extrapair offspring were more heterozygous than
      their within-pair half siblings, and corroborated the previous finding of
      enhanced cellular immunity in extrapair offspring in this four-year dataset. The
      increased heterozygosity among extrapair offspring appeared to be a result of
      extrapair mates being less genetically similar than pair mates, and also less
      genetically similar than expected by random choice. Together with previous
      findings in this species, showing that the majority of females participate in
      extrapair copulations, our results indicate a postcopulatory cryptic female
      choice of genetically dissimilar males. The enhanced cellular immunity and
      increased heterozygosity were not related to each other, and hence our results
      indicate two independent genetic benefits of extrapair mating in the bluethroat.

PMID- 18053074
TI  - Life-history evolution when Lestes damselflies invaded vernal ponds.
AB  - We know little about the macroevolution of life-history traits along
      environmental gradients, especially with regard to the directionality compared to
      the ancestral states and the associated costs to other functions. Here we examine
      how age and size at maturity evolved when Lestes damselflies shifted from their
      ancestral temporary pond habitat (i.e., ponds that may dry once every decade or
      so) to extremely ephemeral vernal ponds (ponds that routinely dry completely each
      year). Larvae of three species were reared from eggs until emergence under
      different levels of photoperiod and transient starvation stress. Compared to the
      two temporary-pond Lestes, the phylogenetically derived vernal-pond Lestes dryas
      developed more rapidly across photoperiod treatments until the final instar, and
      only expressed plasticity in development time in the final instar under
      photoperiod levels that simulated a later hatching date. The documented change in
      development rate can be considered adaptive and underlies the success of the
      derived species in vernal ponds. Results suggest associated costs of faster
      development are lower mass at maturity and lower immune function after transient
      starvation stress. These costs may not only have impeded further evolution of the
      routine development rate to what is physiologically maximal, but also maintained
      some degree of plasticity to time constraints when the habitat shift occurred.

PMID- 18053075
TI  - Experimentally replicated disruptive selection on performance traits in a
      Caribbean lizard.
AB  - A central theme underlying studies of adaptive radiation is that ecologically
      mediated selection drives diversification. However, demonstrating the ecological
      basis of natural selection and linking this process to patterns of morphological
      diversity represents a formidable challenge. This is because selection
      experiments that test correlations between an organism's phenotype and its
      ecology are difficult to perform in the wild. Previous studies of Anolis lizards
      have shown that divergent morphologies are correlated with habitat use and have
      evolved repeatedly on islands throughout the Greater Antilles. Here, we show that
      the forms of selection acting within a species support an ecological mechanism
      for diversification. In natural populations, performance-related traits such as
      limb length are subject to correlational and disruptive selection driven by
      differences in habitat use. Experimental manipulations in the wild verify the
      same pattern of selection and indicate that both the targets and forms of
      selection are consistent through time. Elsewhere, we have demonstrated that these
      traits are heritable and should therefore evolve in response to selection. Our
      results provide evidence for the short-term repeatability of selection and its
      potency in the diversification of anoles.

PMID- 18053076
TI  - The genetic architecture of a female sexual ornament.
AB  - Understanding the evolution of sexual ornaments, and particularly that of female
      sexual ornaments, is an enduring challenge in evolutionary biology. Key to this
      challenge are establishing the relationship between ornament expression and
      female reproductive investment, and determining the genetic basis underpinning
      such relationship. Advances in genomics provide unprecedented opportunities to
      study the genetic architecture of sexual ornaments in model species. Here, we
      present a quantitative trait locus (QTL) analysis of a female sexual ornament,
      the comb of the fowl, Gallus gallus, using a large-scale intercross between red
      junglefowl and a domestic line, selected for egg production. First, we
      demonstrate that female somatic investment in comb reflects female reproductive
      investment. Despite a trade-off between reproductive and skeletal investment
      mediated by the mobilization of skeletal minerals for egg production, females
      with proportionally large combs also had relatively high skeletal investment.
      Second, we identify a major QTL for bisexual expression of comb mass and several
      QTL specific to female comb mass. Importantly, QTL for comb mass were nonrandomly
      clustered with QTL for female reproductive and skeletal investment on chromosomes
      one and three. Together, these results shed light onto the physiological and
      genetic architecture of a female ornament.

PMID- 18053077
TI  - What use is an infertile sperm? A comparative study of sperm-heteromorphic
      Drosophila.
AB  - Sperm size and number are important determinants of male reproductive success.
      The genus Drosophila exhibits a remarkable diversity of sperm production
      strategies, including the production of multiple sperm morphs by individual
      males, a phenomenon called sperm heteromorphism. Sperm-heteromorphic Drosophila
      species in the obscura group produce large numbers of infertile "parasperm" in
      addition to fertile eusperm. Parasperm have been hypothesized to perform a number
      of roles in place of fertilization, predominantly focused on their potential
      function in postcopulatory sexual selection. However, the evolutionary
      significance of parasperm remains unknown. Here we measured several male and
      female morphological, behavioral, and life-history traits in 13 obscura group
      species to test competing hypotheses of parasperm function using comparative
      methods. We found that parasperm size was unrelated to female reproductive tract
      morphology but was negatively related to our two indices of sperm competition,
      suggesting that postcopulatory sexual selection may indeed have shaped the
      evolution of parasperm. We also found abundant coevolution between male and
      female reproductive traits. Some of these relationships have been found in both
      sperm-monomorphic and sperm-heteromorphic taxa, but others are dissimilar. We
      discuss the significance of our results to the evolution of reproductive traits
      and the elusive function of Drosophila parasperm.

PMID- 18053078
TI  - Relic thermosensitive gene expression in a turtle with genotypic sex
      determination.
AB  - The evolution of sex determination remains one of the most fascinating enigmas in
      biology. Transitions between genotypic sex determination (GSD) and temperature
      dependent sex determination (TSD) have occurred multiple times during vertebrate
      evolution, however, the molecular basis and consequences of these transitions in
      closely related taxa remain unresolved. Here I address a critical question: Do
      species with GSD derived from ancestors possessing TSD retain any ancestral
      thermal sensitivity in the developmental pathways underlying gonadal
      differentiation? Results from an expression study of a gene involved in early
      gonadogenesis in GSD (Apalone mutica) and TSD (Chrysemys picta) turtles, support
      the hypothesis that Wt1 in A. mutica displays such a relic thermal sensitivity.
      This retention is likely enabled by Sf1, a gene immediately downstream from Wt1
      whose expression is independent of temperature in this species. My results
      constitute the first empirical evidence of a GSD vertebrate exhibiting thermal
      sensitivity in the expression of a gene regulating gonadogenesis. This novel
      finding reveals an undocumented source of raw material for future evolutionary
      change that may exist in other GSD taxa, and one that enhances the evolutionary
      potential of the gene networks underlying sexual differentiation and contributes
      to the astonishing ability of sex-determining mechanisms.

PMID- 18053079
TI  - Blocking endogenous peroxidases: a cautionary note for immunohistochemistry.

PMID- 18053081
TI  - The ginsenoside metabolite compound K, a novel agonist of glucocorticoid
      receptor, induces tolerance to endotoxin-induced lethal shock.
AB  - Compound K (C-K), a protopanaxadiol ginsenoside metabolite, was previously shown
      to have immunomodulatory effects. Here, we describe a novel therapeutic role for
      C-K in the treatment of lethal sepsis through the modulation of Toll-like
      receptor (TLR) 4-associated signalling via glucocorticoid receptor (GR) binding.
      In mononuclear phagocytes, C-K significantly repressed the activation of
      TLR4/lipopolysaccharide (LPS)-induced NF-kappaB and mitogen-activated protein
      kinases (MAPKs), as well as the secretion of pro-inflammatory cytokines. However
      C-K did not affect the TLR3-mediated expression of interferon-beta or the nuclear
      translocation of IRF-3. C-K competed with the synthetic glucocorticoid
      dexamethasone for binding to GR and activated glucocorticoid responsive element
      (GRE)-containing reporter plasmids in a dose-dependent manner. In addition, the
      blockade of GR with either the GR antagonist RU486 or a siRNA against GR
      substantially reversed the anti-inflammatory effects of C-K. Furthermore, TLR4
      dependent repression of inflammatory response genes by C-K was mediated through
      the disruption of p65/interferon regulatory factor complexes. Importantly, pre-
      or post-treatment with C-K significantly rescued mice from Gram-negative
      bacterial LPS-induced lethal shock by lowering their systemic inflammatory
      cytokine levels and by reversing the lethal sequelae of sepsis. Collectively,
      these results demonstrate that C-K, as a functional ligand of GR, regulates
      distinct TLR4-mediated inflammatory responses, and suggest a novel therapy for
      Gram-negative septic shock.

PMID- 18053083
TI  - The unfolded protein response in hereditary haemochromatosis.
AB  - To cope with the accumulation of unfolded or misfolded proteins the endoplasmic
      reticulum (ER) has evolved specific signalling pathways collectively called the
      unfolded protein response (UPR). Elucidation of the mechanisms governing ER
      stress signalling has linked this response to the regulation of diverse
      physiologic processes as well as to the progression of a number of diseases.
      Interest in hereditary haemochromatosis (HH) has focused on the study of proteins
      implicated in iron homeostasis and on the identification of new alleles related
      with the disease. HFE has been amongst the preferred targets of interest, since
      the discovery that its C282Y mutation was associated with HH. However, the
      discrepancies between the disease penetrance and the frequency of this mutation
      have raised the possibility that its contribution to disease progression might go
      beyond the mere involvement in regulation of cellular iron uptake. Recent
      findings revealed that activation of the UPR is a feature of HH and that this
      stress response may be involved in the genesis of immunological anomalies
      associated with the disease. This review addresses the connection of the UPR with
      HH, including its role in MHC-I antigen presentation pathway and possible
      implications for new clinical approaches to HH.

PMID- 18053084
TI  - Oval cell proliferation in p16INK4a expressing mouse liver is triggered by
      chronic growth stimuli.
AB  - Terminal differentiation requires molecules also involved in aging such as the
      cell cycle inhibitor p16(INK4a). Like other organs, the adult liver represents a
      quiescent organ with terminal differentiated cells, hepatocytes and
      cholangiocytes. These cells retain the ability to proliferate in response to
      liver injury or reduction of liver mass. However, under conditions which prevent
      mitotic activation of hepatocytes, regeneration can occur instead from
      facultative hepatic stem cells.For therapeutic application a non-toxic activation
      of this stem cell compartment is required. We have established transgenic mice
      with conditional overexpression of the cell cycle inhibitor p16(INK4a) in
      hepatocytes and have provoked and examined oval cell activation in adult liver in
      response to a range of proliferative stimuli. We could show that the liver
      specific expression of p16(INK4a) leads to a faster differentiation of
      hepatocytes and an activation of oval cells already in postnatal mice without
      negative consequences on liver function.

PMID- 18053086
TI  - Pleomorphism of the nuclear envelope in breast cancer: a new approach to an old
      problem.
AB  - In routine practice, nuclear pleomorphism of tumours is assessed by haematoxylin
      staining of the membrane-bound heterochromatin. However, decoration of the
      nuclear envelope (NE) through the immunofluorescence staining of NE proteins such
      as lamin B and emerin can provide a more objective appreciation of the nuclear
      shape. In breast cancer, nuclear pleomorphism is one of the least reproducible
      parameters to score histological grade, thus we sought to use NE proteins to
      improve the reproducibility of nuclear grading. First, immuno-fluorescence
      staining of NE as well as confocal microscopy and three-dimensional
      reconstruction of nuclei in cultured cells showed a smooth and uniform NE of
      normal breast epithelium in contrast to an irregular foldings of the membrane and
      the presence of deep invaginations leading to the formation of an intranuclear
      scaffold of NE-bound tubules in breast cancer cells. Following the above methods
      and criteria, we recorded the degree of NE pleomorphism (NEP) in a series of 273
      invasive breast cancers tested by immunofluorescence. A uniform nuclear shape
      with few irregularities (low NEP) was observed in 135 cases or, alternatively,
      marked folds of the NE and an intranuclear tubular scaffold (high NEP cases) were
      observed in 138 cases. The latter features were significantly correlated (P-value
      <0.002) with lymph node metastases in 54 histological grade 1 and in 173 cancers
      with low mitotic count. Decoration of the NE might thus be regarded as a novel
      diagnostic parameter to define the grade of malignancy, which parallels and
      enhances that provided by routine histological procedures.

PMID- 18053089
TI  - NFkappaB mediates IL-1beta-induced down-regulation of TbetaRII through the
      modulation of Sp3 expression.
AB  - We previously showed that interleukin-1beta (IL-1beta) down-regulation of type II
      TGFbeta receptor (TbetaRII) involves NFkappaB pathway and requires de novo
      synthesis of a yet unknown protein. Here, we demonstrate that this effect is
      mediated through Sp1 site located at position -25 of human TbetaRII promoter.
      Inhibition of transcription factors binding (decoy oligonucleotides or
      mithramycin) abolished IL-1beta effect. EMSA and ChIP revealed that this
      treatment induced Sp3 binding to cis-sequence whereby IL-1beta exerts its
      transcriptional effects whereas it decreased that of Sp1. Moreover, although the
      cytokine did not modulate Sp1 expression, it increased that of Sp3 via NFkappaB
      pathway. Experiments of gain and loss of function clearly showed that Sp3
      inhibited TbetaRII expression whereas its silencing abolished IL-1beta effect. In
      addition, both Sp1 and Sp3 were found to interact with NFkappaB, which therefore
      may indirectly interact with TbetaRII pro moter. Altogether, these data suggest
      that IL-1beta decreases TbetaRII expression by inducing Sp3 via NFkappaB and its
      binding on core promote at the expense of Sp1, which could explain the loss of
      cell responsiveness in certain conditions. These findings bring new insights in
      the knowledge of the interference between two antagonistic transduction pathways
      involved in multiple physiopathological processes.

PMID- 18053090
TI  - Acidic pre-conditioning suppresses apoptosis and increases expression of Bcl-xL
      in coronary endothelial cells under simulated ischaemia.
AB  - Ischaemic pre-conditioning has a powerful protective potential against ischaemia
      induced cell death, and acidosis is an important feature of ischaemia and can
      lead to apoptosis. Here we tested whether pre-conditioning with acidosis, that
      is, acidic pre-conditioning (APC), may protect coronary endothelial cells (EC)
      against apoptosis induced by simulated ischaemia. For pre-conditioning, EC were
      exposed fo 40 min. to acidosis (pH 6.4) followed by a 14-hrs recovery period (pH
      7.4) and finally treated for 2 hrs with simulated ischaemia (glucose-free anoxia
      at pH 6.4). Cells undergoing apoptosis were visualized by chromatin staining or
      by determination of caspase-3 activity Simulated ischaemia in untreated EC
      increased caspase-3 activity and the number of apoptotic cell (31.3 +/-
      1.3%versus 3.9 +/- 0.6% in control). APC significantly reduced the rate of
      apoptosis (14.2 +/- 1.3%) and caspase-3 activity. Western blot analysis exploring
      the under lying mechanism leading to this protection revealed suppression of the
      endoplasmic reticulum- (reduced cleavage of caspase-12) and mitochondria-mediated
      (reduced cytochrome C release) pathways of apoptosis. These effects were
      associated with an over-expression of the anti-apoptotic protein Bcl-xL 14 hrs
      after APC, whereas no effect on the expression of Bcl-2, Bax, Bak, procaspase-12,
      reticulum-localized chaperones (GRP78, calreticulin), HSP70, HSP32 and HSP27
      could be detected. Knock-down of Bcl-xL by siRNA-treatment prevented the
      protective effect of APC. In conclusion, short acidic pre-treatment can protect
      EC against ischaemic apoptosis. The mechanism of this protection consists of
      suppression of the endoplasmic reticulum- and mitochondria-mediated pathways.
      Over-expression of the anti apoptotic protein Bcl-xL is responsible for the
      increased resistance to apoptosis during ischaemic insult.

PMID- 18053085
TI  - The glucocorticoid receptor signalling in breast cancer.
AB  - Glucocorticoids are provided as co-medication with chemotherapy in breast cancer,
      albeit several lines of evidence indicate that their use may have diverse effects
      and in fact may inhibit chemosensitivity. The molecular basis of glucocorticoid
      induced resistance to chemotherapy in breast cancer remains poorly defined.
      Recent researchers, in an attempt to clarify some aspects of the underlying
      pathways, provide convincing evidence that glucocorticoids induce effects that
      are dependent upon the glucocorticoid receptor -mediated transcriptional
      regulation of specific genes known to play key roles in cellular/tissue
      functions, including growth, apoptosis, differentiation, metastasis and cell
      survival. In this review, we focus on how glucocorticoid-induced chemoresistance
      in breast cancer is mediated by the glucocorticoid receptor, unraveling the
      molecular interplay of glucocorticoid receptor signaling with other signaling
      cascades prevalent in breast cancer. We also include a detailed description of
      glucocorticoid receptor structure and function, summarizing data gained during
      recent years into the mechanism(s) of the cross-talk between the glucocorticoid
      receptor and other signaling cascades and secondary messengers, via which
      glucocorticoids exert their pleiotropic effects.

PMID- 18053091
TI  - Regulatory roles for histone deacetylation in IL-1beta-induced nitric oxide
      release in pancreatic beta-cells.
AB  - Histone (de)acetylases control gene transcription via modification of the
      chromatin structure. Herein, we investigated potential roles for histone
      deacetylation (or hypoacetylation) in interleukin-1beta (IL-1beta)-mediated
      inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release in insulin
      secreting INS 832/13 (INS) cells. Western blot analysis suggested localization of
      members of Class 1 and Class 2 families of histone deacetylases (HDACs) in these
      cells. Trichostatin A (TSA), a known inhibitor of HDACs, markedly reduced IL
      1beta-mediated iNOS expression and NO release from these cells in a concentration
      dependent manner. TSA also promoted hyperacetylation of histone H4 under
      conditions in which it inhibited IL-1beta-mediated effects on isolated beta
      cells. Rottlerin, a known inhibitor of protein kinase Cdelta, also increased
      histone H4 acetylation, and inhibited IL-1beta-induced iNOS expression and NO
      release in these cells. It appears that the putative mechanism underlying the
      stimulatory effects of rottlerin on acetylation status of histone H4 are distinct
      from the HDAC inhibitory property of TSA, since rottlerin failed to inhibit HDAC
      activity in nuclear extracts isolated from INS cells. These data are suggestive
      of potential regulatory effects of rottlerin at the level of increasing the
      histone acetyltransferase activity in these cells. Together our studies present
      the first evidence to suggest a PKCdelta-mediated signalling step, which promotes
      hypoacetylation of candidate histones culminating in IL-1beta-induced metabolic
      dysfunction of the isolated beta cell.

PMID- 18053093
TI  - Epidermal growth factor increases insulin secretion and lowers blood glucose in
      diabetic mice.
AB  - Epidermal growth factor (EGF) is synthesized in the pancreas and diabetic animals
      have low levels of EGF. However, the role of EGF in regulating the major function
      of the pancreas, insulin secretion, has not been studied. Here, we show that EGF
      rapidly increased insulin secretion in mouse pancreatic islets, as well as in a
      pancreatic beta-cell line. These events were dependent on a Ca(2+) influx and
      phospholipase D (PLD) activity, particularly PLD2, as determined using
      pharmacological blockers and molecular manipulations such as over-expression and
      siRNA of PLD isozymes. In addition, EGF also increased plasma insulin levels and
      mediated glucose lowering in normal and diabetic mice. Here, for the first time,
      we provide evidence that EGF is a novel secretagogue that regulates plasma
      glucose levels and a candidate for the development of therapeutics for diabetes.

PMID- 18053094
TI  - Protein prenylation in glucose-induced insulin secretion from the pancreatic
      islet beta cell: a perspective.
AB  - Insulin secretion from the pancreatic beta-cell is regulated principally by the
      ambient concentration of glucose. However, the molecular and cellular mechanisms
      underlying the stimulus-secretion coupling of glucose-stimulated insulin
      secretion (GSIS) remain only partially understood. Emerging evidence from
      multiple laboratories suggests key regulatory roles for GTP-binding proteins (G
      proteins) in the cascade of events leading to GSIS. This class of signaling
      proteins undergo a series of requisite post-translational modifications (e.g.,
      prenylation) at their C-terminal cysteines, which appear to be necessary for
      their targeting to respective membranous sites for optimal interaction with their
      respective effector proteins. This communication represents a perspective on
      potential regulatory roles for protein prenylation steps (i.e., protein
      farnesylation and protein geranylgeranylation) in GSIS from the islet beta cell.
      Possible consequences of protein prenylation and potential mechanisms underlying
      glucose-induced regulation of prenylation, specifically in the context of GSIS
      are also discussed.

PMID- 18053095
TI  - Caveolin-1 is transported to multi-vesicular bodies after albumin-induced
      endocytosis of caveolae in HepG2 cells.
AB  - Caveolae-mediated endocytosis is a highly regulated endocytic pathway that exists
      in parallel to other forms of clathrin-dependent and -independent endocytosis.
      Internalized caveolae accumulate in intermediate organelles called caveosomes.
      Here we addressed the further fate of internalized caveolae by inducing caveolae
      mediated uptake of albumin by HepG2 cells. We followed the route of internalized
      caveolin-1 by immunogold labelling of ultrathin frozen sections and by Western
      blot analyses of purified membrane fractions. Long-term (1 and 3 hrs) albumin
      treatment resulted in the appearance of albumin-containing caveolae in special
      multi-caveolar complexes (consisting of multiple caveolae clustered together)
      connected to the plasma membrane and caveosome-like structures in the cytoplasm.
      In addition, numerous CD63 (LIMP-1) positive late endosomes/multi-vesicular
      bodies were found positive for caveolin-1, suggesting that upon albumin
      incubation, caveolin-1 is endocytosed and enters the degradative pathway.
      Surprisingly, the number of caveolae at the plasma membrane increased after
      addition of albumin. This increase was blocked by cycloheximide treatment,
      indicating that albumin internalization also stimulates de novo protein
      synthesis, which is necessary for new caveolae formation. Together, our results
      show that during long-term albumin uptake, caveolin-1 travels to late endosomes
      and is replaced by newly synthesized caveolin-1 at the plasma membrane.

PMID- 18053097
TI  - A fishy recommendation: omega-3 fatty acid intake in pregnancy.

PMID- 18053092
TI  - Cancer stem cells: the lessons from pre-cancerous stem cells.
AB  - How a cancer is initiated and established remains elusive despite all the
      advances in decades of cancer research. Recently the cancer stem cell (CSC)
      hypothesis has been revived, challenging the long-standing model of "clonal
      evolution" for cancer development and implicating the dawning of a potential cure
      for cancer [1]. The recent identification of precancerous stem cells (pCSCs) in
      cancer, an early stage of CSC development, however, implicates that the "clonal
      evolution" is not contradictory to the CSC hypothesis, but is rather an aspect of
      the process of CSC development [2]. The discovery of pCSC has revealed and will
      continue to reveal the volatile properties of CSC with respects to their
      phenotype, differentiation and tumorigenic capacity during initiation and
      progression. Both pCSC and CSC might also serve as precursors of tumor stromal
      components such as tumor vasculogenic stem/progenitor cells (TVPCs). Thus, the
      CSC hypothesis covers the developing process of tumor-initiating cells (TIC) -->
      pCSC --> CSC --> cancer, a cellular process that should parallel the histological
      process of hyperplasia/metaplasia (TIC) --> precancerous lesions (pCSC) -->
      malignant lesions (CSC --> cancer). The embryonic stem (ES) cell and germline
      stem (GS) cell genes are subverted in pCSCs. Especially the GS cell protein
      piwil2 may play an important role during the development of TIC --> pCSC --> CSC,
      and this protein may be used as a common biomarker for early detection,
      prevention, and treatment of cancer. As cancer stem cell research is yet in its
      infancy, definitive conclusions regarding the role of pCSC can not be made at
      this time. However this review will discuss what we have learned from pCSC and
      how this has led to innovative ideas that may eventually have major impacts on
      the understanding and treatment of cancer.

PMID- 18053098
TI  - Manual versus electric vacuum aspiration for first-trimester abortion: a
      systematic review.
AB  - BACKGROUND: As an alternative to electric vacuum aspirations (EVA), there is an
      increasing interest in using manual vacuum aspiration (MVA). OBJECTIVE: To
      compare the safety, efficacy and acceptability of MVA with those of EVA for first
      trimester abortion. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Cochrane
      Library and Chinese Biomedical Database in all language, together with reference
      lists of retrieved papers. SELECTION CRITERIA: Randomised controlled trials
      comparing MVA with EVA for first-trimester abortion were included. The outcomes
      are complete abortion rate, uterine perforation rate, blood loss, pain perception
      and acceptability. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      extracted the data. Results from the trials were combined to calculate relative
      risks (RRs) or risk differences for dichotomous outcomes and weighted mean
      differences (WMDs) for continuous outcomes, together with 95% CIs. MAIN RESULTS:
      Ten trials were included, involving 1660 women. Generally, the methodological
      quality was poor. There were no statistically significant differences, comparing
      MVA with EVA, in complete abortion rate (RR 1.00; 95% CI 0.99-1.02) and
      participants' satisfaction (RR 1.02; 95% CI 0.87-1.20). In participants with less
      than 50 days of gestational age, less blood loss (WMD -1.84; 95% CI -2.45 to 
      1.23) and less severe pain perception (RR 0.04; 95% CI 0.01-0.12) were reported
      during the MVA procedure, whereas the operation time was shorter (WMD 0.32; 95%
      CI 0.02-0.63) in the EVA procedure. AUTHOR'S CONCLUSIONS: There is some evidence
      that MVA is as effective and acceptable as EVA and might be safer than EVA.

PMID- 18053099
TI  - Nitric oxide and peroxynitrite platelet levels in women with small-for
      gestational-age fetuses.
AB  - OBJECTIVE: The placenta produces reactive oxygen species (ROS) including nitric
      oxide (NO) and peroxynitrite (ONOO(-)) that have pronounced effects on placental
      function. Excessive ROS production may occur in pathological pregnancies, such as
      those complicated by small-for-gestational-age (SGA) fetuses. DESIGN: The aim of
      the present work was to study NO and ONOO(-) levels in platelets of pregnant
      women with SGA fetuses compared with a control group. SETTING AND POPULATION: The
      study was performed on 30 pregnant women with SGA fetuses (SGA group) and on 30
      healthy pregnant women (appropriate-for-gestational-age [AGA] group) matched for
      maternal and gestational age. All women included in this study were in the third
      trimester of pregnancy. METHODS: Platelets were isolated by differential
      centrifugation. NO metabolites, after enzymatic conversion followed by the Griess
      reaction, were measured as nitrite by spectrophotometric detection. Peroxynitrite
      (ONOO(-)) levels were evaluated using the fluorescence probe 2,7
      dichlorofluorescein diacetate (DCFDA). MAIN OUTCOME MEASURES: The following
      determinations were made: platelet nitric oxide and peroxynitrite levels in the
      SGA group and controls; inducible nitric oxide synthase (iNOS), endothelial
      nitric oxide synthase (eNOS) and nitrotyrosine (N-Tyr) expression in the same
      groups. RESULTS: Our results show that both platelet NO and ONOO(-) levels were
      significantly higher in the SGA group than in the controls. CONCLUSION: Increased
      platelets levels of nitric oxide and peroxynitrite might play a role in the
      pathophysiology of intrauterine growth restriction. Further investigations are in
      progress to clarify if these molecules are pathogenetic factors, an epiphenomenon
      or a pathophysiological marker.

PMID- 18053100
TI  - Retrospective multicentre study of the new minimally invasive mesh repair devices
      for pelvic organ prolapse.
AB  - OBJECTIVES: To assess the complications and short-term outcomes of prolapse
      repair mesh devices used in the management of female pelvic organ prolapse (POP).
      DESIGN: Retrospective cohort study. SETTING: Multicentre study involving a
      tertiary referral urogynaecology unit and two district general hospitals.
      POPULATION: 329 women who underwent surgical management of prolapse with various
      prolapse repair mesh devices in the period between January 2005 and December
      2006. METHODS: Women were identified from theatre records. An independent
      clinician performed a case notes review during the period March to May 2007. MAIN
      OUTCOME MEASURES: Complication rates and the short-term cure at 3-month follow-up
      (defined as </=stage I prolapse on the POP-Q or Baden Walker scoring systems).
      RESULTS: A total of 289 women were included: 219 (76%) used the Gynecare prolapse
      repair mesh devices, while 70 women (24%) used the American Medical Systems
      prolapse repair mesh devices. Operative complications included: bladder injury
      (1.6%), rectal injury (1.1%) and two women with serious vascular injuries.
      Postoperative complications included: buttock pain (5.2%), vaginal erosion (10%),
      one woman with bladder erosion and two women (0.7%) with serious infection,
      leading to necrotising fasciitis in one woman. Short-term cure rates in different
      groups varied from 94 to 100%, depending on vaginal compartment and device used.
      In total 15 women (5%) had persistent prolapse at 3-month follow up. CONCLUSION:
      The new prolapse repair mesh devices demonstrate excellent short-term cure and
      low morbidity rates. However, some complications are serious and require highly
      specialised management. Rigorous evaluation by means of independent, controlled
      studies is urgently required.

PMID- 18053101
TI  - A survey of women's views of Thermachoice endometrial ablation in the outpatient
      versus day case setting.
AB  - OBJECTIVE: To determine women's preference towards Thermachoice being performed
      either awake in the outpatient setting or under general anaesthetic (GA) as a day
      case. DESIGN: Questionnaire. Setting Large teaching hospital. POPULATION: One
      hundred women. METHODS: The questionnaire was developed from prior research on
      factors associated with preference for procedures performed in the outpatient
      versus day case setting. MAIN OUTCOME MEASURES: (1) Describe women's preference
      towards outpatient versus day case Thermachoice and other menorrhagia treatments.
      (2) Identify variations in preference by demographic characteristics and prior
      experience of anaesthesia. Results There was an exact split in preference with
      50% preferring Thermachoice as an outpatient and 50% as a day case. The mean age
      of women preferring outpatient Thermachoice was significantly higher (41.5 years)
      than those preferring day case (33.5 years) (P < 0.005). Women with children and
      a higher qualification were more likely to opt for outpatient Thermachoice. A
      previous bad experience of GA was associated with preference for outpatient
      Thermachoice. Spending less time in hospital, attending for one visit, feeling
      well straight after treatment and choosing the treatment setting were important
      factors to the majority of women. Most women (70%) who opted for Thermachoice as
      a menorrhagia treatment would prefer to have it performed in the outpatient
      setting. CONCLUSIONS: If the Department of Heath is to target services towards
      women's choice, there is a need to increase the provision of outpatient
      menorrhagia treatments, such as Thermachoice, to more women in the UK.

PMID- 18053102
TI  - The incidence of preterm deliveries decreases in Finland.
AB  - OBJECTIVE: We examined the trends and risk factors of preterm delivery. DESIGN:
      Register-based retrospective cohort study from Finland. SETTING: National Medical
      Birth Register data during 1987-2005. POPULATION: The study population consisted
      of 1 137 515 deliveries, of which 59 025 were preterm (5.2%). METHODS: We
      calculated the population attributable risks for using the risk factor prevalence
      rates in the population. We further calculated odds ratios with 95% CI by
      multivariate logistic regression to adjust for confounders. MAIN OUTCOME
      MEASURES: Preterm delivery rate subclassified into moderately preterm (32-36
      weeks), very preterm (28-31 weeks) and extremely preterm (less than 28 weeks).
      RESULTS; Preterm delivery rates increased from 5.1% in the late 1980s to 5.4% in
      the late 1990s but then decreased to 5.2% for 2001-05. The proportion of
      extremely preterm deliveries decreased substantially by 12% (P < 0.01). The
      greatest risk factors were multiplicity (OR 13.72, 95% CI 13.26-14.19), followed
      by elective delivery (OR 1.86, 95% CI 1.82-1.89), primiparity (OR 1.47, 95% CI
      1.45-1.50), in vitro fertilisation treatment (OR 1.39, 95% CI 1.31-1.47),
      maternal smoking (OR 1.31, 95% CI 1.29-1.34) and advanced maternal age (OR 1.02,
      95% CI 1.02-1.03 for each additional year of age). Prematurity rates decreased by
      1.8% after adjusting for risk variables. CONCLUSIONS: The rate of preterm
      delivery has not increased from 1987 to 2005 in Finland, while the risk for
      extremely preterm delivery has decreased. This finding is in contrast with recent
      trends in other countries.

PMID- 18053103
TI  - Thrombocytopenia in hydropic fetuses with parvovirus B19 infection: incidence,
      treatment and correlation with fetal B19 viral load.
AB  - OBJECTIVE: To examine (1) the incidence of fetal thrombocytopenia in hydropic
      fetuses with congenital B19 virus infection, (2) the effect of intrauterine
      platelet transfusions and (3) the correlation between fetal B19 viral load and
      severity of thrombocytopenia. DESIGN: Retrospective analysis of data from
      prospectively collected fetal blood samples. SETTING: Leiden University Medical
      Centre, the national centre for management of intrauterine fetal disease in the
      Netherlands. POPULATION: Thirty hydropic fetuses treated with intrauterine red
      blood cell and platelet transfusions for human B19 virus-induced severe fetal
      anaemia and thrombocytopenia over a 10-year period. METHODS: Fetal blood samples
      (n= 30) taken before and after intrauterine transfusion were investigated. No
      cases were excluded, and there was no loss to follow up. MAIN OUTCOME MEASURES:
      Parameters recorded were gestational age, experienced fetal movements, gravidity
      and parity, severity of fetal hydrops, severity of fetal anaemia and
      thrombocytopenia and megakaryocyte and reticulocyte counts. Survival and
      procedure-associated complications were documented. Quantitative B19 viral load
      measurements were performed on all fetal samples. RESULTS: Forty-six percent of
      all hydropic fetuses showed severe thrombocytopenia. No antenatal intracerebral
      haemorrhage or procedure-associated bleeding occurred. Overall, survival was 77%.
      Platelet counts increased following platelet transfusion and decreased
      significantly following red blood cell transfusion alone. No correlation was
      found between fetal viral loads and platelet counts. CONCLUSION: Thrombocytopenia
      was frequently encountered in fetal B19V infection, but fetal bleeding
      complications were not noted. Absence of a direct relationship between fetal B19
      viral load and platelet counts suggests a temporal dissociation between these
      findings. Dilutional thrombocytopenia is frequently seen in the fetus following
      red blood cell transfusion alone. The clinical significance of this phenomenon is
      unclear. The risk of fluid overload by fetal platelet transfusion in a severely
      hydropic fetus should be weighed against the low incidence of fetal bleeding
      complications.

PMID- 18053104
TI  - Social inequalities in preterm birth in Scotland 1980-2003: findings from an area
      based measure of deprivation.
AB  - OBJECTIVE: The preterm birth rate in Scotland has been increasing in recent
      years. Although preterm birth rates show a social gradient, it is unclear how
      this gradient has been affected by the overall increase. We examined time trends
      in singleton live preterm birth rates in relation to area-based socio-economic
      indicators. DESIGN: Population-based retrospective cohort study. SETTING:
      Scotland. PARTICIPANTS: All singleton live births delivered in Scottish hospitals
      between 1980 and 2003 (n= 1 423 993). MAIN OUTCOME MEASURES: Singleton live
      preterm birth rates in each deprivation quintile were derived. Subgroup analyses
      of those born moderately preterm (32-36 weeks), very preterm (28-31 weeks) and
      extremely preterm (24-27 weeks) were performed. RESULTS: The rate of singleton
      live preterm births increased from 49.7 per 1000 live births in the 5-year period
      1980-84 to 56.1 per 1000 in the 4-year period 2000-03, a relative increase of
      12.9%. A marked social gradient was apparent at all time periods: relative
      indices of inequality were 1.63 (95% CI 1.38-1.92) in 1980-84 and 1.55 (1.44
      1.66) in 2000-03. Similar social gradients existed for all gestational age
      subgroups. Smoking status at first antenatal contact and increased obstetric
      intervention, possibly reflecting improvements in fetal monitoring and neonatal
      care, appeared to explain some but not all the social gradient. CONCLUSIONS:
      Social inequalities in preterm birth were apparent in Scotland between 1980 and
      2003. In addition to helping pregnant women to stop smoking, other means to
      reduce social inequalities are required.

PMID- 18053105
TI  - Effect of narghile and cigarette smoking on newborn birthweight.
AB  - OBJECTIVE: To assess the effect of narghile smoking on the weight of newborns.
      DESIGN: Historical retrospective cohort. SETTING: Six major hospitals in Greater
      Beirut, Lebanon. POPULATION: Consecutive singleton newborns delivered from August
      2000 to August 2003. METHODS: Obstetric and nursery charts were reviewed to
      obtain information about maternal and neonatal variables. Information concerning
      initiation of smoking, dose of smoking, smoking habits during pregnancy, and
      socio-demographic characteristics was collected through interviews with mothers.
      MAIN OUTCOME MEASURES: Low birthweight and newborn birthweight. RESULTS:
      Exclusive narghile smokers constituted 4.4% (378/8592) of women. Multiparas were
      significantly more likely to smoke cigarettes and narghile. Mothers smoking
      narghile more than once per day were at 2.4 increased odds of having low
      birthweight infants compared with nonsmoking mothers (OR 2.4; 95% CI 1.2-5.0)
      after adjusting for confounding variables. No difference was noted between women
      smoking narghile in the first trimester and those initiating smoking in
      subsequent trimesters regarding low birthweight. CONCLUSIONS: Narghile smoking
      more than once per day increases the odds of low birthweight by a 2.4-fold
      compared with nonsmokers, although to a lesser extent than cigarette smoking.

PMID- 18053107
TI  - Use of C-reactive protein as a predictor of chorioamnionitis in preterm prelabour
      rupture of the membranes: a systematic review.

PMID- 18053109
TI  - Laparoscopic uterine sling suspension: a new technique of uterine suspension in
      women desiring surgical management of uterine prolapse with uterine conservation.

PMID- 18053111
TI  - Ultrasonographic diagnosis of fetal seizures: a case report and review of the
      literature.

PMID- 18053112
TI  - Retained hormone release capsule following removal of Mirena intrauterine system.

PMID- 18053114
TI  - Laparoscopic uterine sling suspension: a new technique of uterine suspension in
      women desiring surgical management of uterine prolapse with uterine conservation.

PMID- 18053115
TI  - Don't forget OSA with PCOS!

PMID- 18053118
TI  - Abstracts of the 23rd Patient Classifications Systems International (PCSI)
      Working Conference, Venice, Italy, 7-10 November 2007.

PMID- 18053117
TI  - Abstracts from the 3rd International Society for Computational Biology (ISCB)
      Student Council Symposium at the 15th Annual International Conference on
      Intelligent Systems for Molecular Biology (ISMB), Vienna, Austria, 21 July 2007.

PMID- 18053119
TI  - Abstracts of the 13th Scientific Symposium of the Austrian Pharmacological
      Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX)
      and the Hungarian Society for Experimental and Clinical Pharmacology (MFT),
      Vienna, Austria, 22-24 November 2007.

PMID- 18053120
TI  - Growth hormone as concomitant treatment in severe fibromyalgia associated with
      low IGF-1 serum levels. A pilot study.
AB  - BACKGROUND: There is evidence of functional growth hormone (GH) deficiency,
      expressed by means of low insulin-like growth factor 1 (IGF-1) serum levels, in a
      subset of fibromyalgia patients. The efficacy of GH versus placebo has been
      previously suggested in this population. We investigated the efficacy and safety
      of low dose GH as an adjunct to standard therapy in the treatment of severe,
      prolonged and well-treated fibromyalgia patients with low IGF-1 levels. METHODS:
      Twenty-four patients were enrolled in a randomized, open-label, best available
      care-controlled study. Patients were randomly assigned to receive either 0.0125
      mg/kg/d of GH subcutaneously (titrated depending on IGF-1) added to standard
      therapy or standard therapy alone during one year. The number of tender points,
      the Fibromyalgia Impact Questionnaire (FIQ) and the EuroQol 5D (EQ-5D), including
      a Quality of Life visual analogic scale (EQ-VAS) were assessed at different time
      points. RESULTS: At the end of the study, the GH group showed a 60% reduction in
      the mean number of tender points (pairs) compared to the control group (p < 0.05;
      3.25 +/- 0.8 vs. 8.25 +/- 0.9). Similar improvements were observed in FIQ score
      (p < 0.05) and EQ-VAS scale (p < 0.001). There was a prompt response to GH
      administration, with most patients showing improvement within the first months in
      most of the outcomes. The concomitant administration of GH and standard therapy
      was well tolerated, and no patients discontinued the study due to adverse events.
      CONCLUSION: The present findings indicate the advantage of adding a daily GH dose
      to the standard therapy in a subset of severe fibromyalgia patients with low IGF
      1 serum levels. TRIAL REGISTRATION: NCT00497562 (ClinicalTrials.gov).

PMID- 18053121
TI  - Regulation of nestin expression by thrombin and cell density in cultures of bone
      mesenchymal stem cells and radial glial cells.
AB  - BACKGROUND: Bone marrow stromal cells and radial glia are two stem cell types
      with neural phenotypic plasticity. Bone marrow mesenchymal stem cells can
      differentiate into osteocytes, chondrocytes and adipocytes, but can also
      differentiate into non-mesenchymal cell, i.e. neural cells in appropriate in vivo
      and in vitro experimental conditions. Likewise, radial glial cells are the
      progenitors of many neurons in the developing cortex, but can also generate
      astrocytes. Both cell types express nestin, an intermediate filament protein
      which is the hallmark of neural precursors. RESULTS: In this study, we
      demonstrate that thrombin, a multifunctional serine protease, stimulates the
      growth of radial glial cells (RG) and mesenchymal stem cells (MSCs) in a dose
      dependent manner. In RG, the mitogenic effect of thrombin is correlated with
      increased expression of nestin but in MSCs, this mitogenic effect is associated
      with nestin down-regulation. Both cell types express the PAR-1 type receptor for
      Thrombin and the effect of Thrombin on both cell types can be mimicked by its
      analogue TRAP-6 activating specifically this receptor subtype or by serum which
      contains various amount of thrombin. Moreover, we also demonstrate that serum
      deprivation-induced expression of nestin in MSCs is inhibited by high cell
      density (> 50,000 cells/cm2). CONCLUSION: This work shows that thrombin
      stimulates the growth of both RG and MSCs and that nestin expression by MSCs and
      RG is regulated in opposite manner by thrombin in vitro. Thrombin effect is thus
      associated in both cell types with a proliferating, undifferentiated state but in
      RG this involves the induction of nestin expression, a marker of immaturity for
      neural progenitors. In MSCs however, nestin expression, as it corresponds to a
      progression from the mesenchymal "undifferentiated", proliferating phenotype
      toward acquisition of a neural fate, is inhibited by the mitogenic signal.

PMID- 18053122
TI  - A conceptual framework for implementation fidelity.
AB  - BACKGROUND: Implementation fidelity refers to the degree to which an intervention
      or programme is delivered as intended. Only by understanding and measuring
      whether an intervention has been implemented with fidelity can researchers and
      practitioners gain a better understanding of how and why an intervention works,
      and the extent to which outcomes can be improved. DISCUSSION: The authors
      undertook a critical review of existing conceptualisations of implementation
      fidelity and developed a new conceptual framework for understanding and measuring
      the process. The resulting theoretical framework requires testing by empirical
      research. SUMMARY: Implementation fidelity is an important source of variation
      affecting the credibility and utility of research. The conceptual framework
      presented here offers a means for measuring this variable and understanding its
      place in the process of intervention implementation.

PMID- 18053123
TI  - Experimental transmission of Anaplasma marginale by male Dermacentor reticulatus.
AB  - BACKGROUND: Bovine anaplasmosis has been reported in several European countries,
      but the vector competency of tick species for Anaplasma marginale from these
      localities has not been determined. Because of the wide distributional range of
      Dermacentor reticulatus within Europe and the major role of Dermacentor spp. as a
      vector of A. marginale in the United States, we tested the vector competency of
      D. reticulatus for A. marginale. RESULTS: Male D. reticulatus were allowed to
      feed for 7 days on a calf persistently infected with a Zaria isolate of A.
      marginale, after which they were removed and held off-host for 7 days. The ticks
      were then allowed to feed a second time for 7 days on a susceptible tick-naive
      calf. Infection of calf No. 4291 was detected 20 days post exposure (p.i.) and
      confirmed by msp4 PCR. Thirty percent of the dissected acquisition fed ticks was
      infected. In addition, A. marginale colonies were detected by light microscopy in
      the salivary glands of the acquisition fed ticks. Transmission of A. marginale to
      calf No. 9191 was confirmed by examination of Giemsa-stained blood smears and
      msp4 PCR. Ticks were dissected after transmission feeding and presence of A.
      marginale was confirmed in 18.5% of the dissected ticks. CONCLUSION: This study
      demonstrates that D. reticulatus males are competent vectors of A. marginale.
      Further studies are needed to confirm the vector competency of D. reticulatus for
      other A. marginale strains from geographic areas in Europe.

PMID- 18053124
TI  - The Fer tyrosine kinase regulates an axon retraction response to Semaphorin 3A in
      dorsal root ganglion neurons.
AB  - BACKGROUND: Fps/Fes and Fer are the only two members of a distinct subclass of
      cytoplasmic protein tyrosine kinases. Fps/Fes was previously implicated in
      Semaphorin 3A (Sema3A)-induced growth cone collapse signaling in neurons from the
      dorsal root ganglion (DRG) through interaction with and phosphorylation of the
      Sema3A receptor component PlexinA1, and members of the collapsin response
      mediator protein (CRMP) family of microtubule regulators. However, the potential
      role of the closely related Fer kinase has not been examined. RESULTS: Here we
      provide novel biochemical and genetic evidence that Fer plays a prominent role in
      microtubule regulation in DRG neurons in response to Sema3A. Although Fps/Fes and
      Fer were both expressed in neonatal brains and isolated DRGs, Fer was expressed
      at higher levels; and Fer, but not Fps/Fes kinase activity was detected in vivo.
      Fer also showed higher in vitro kinase activity toward tubulin, as an exogenous
      substrate; and this activity was higher when the kinases were isolated from
      perinatal relative to adult brain stages. CRMP2 was a substrate for both kinases
      in vitro, but both CRMP2 and PlexinA1 inhibited their autophosphorylation
      activities. Cultured mouse DRG neurons retracted their axons upon exposure to
      Sema3A, and this response was significantly diminished in Fer-deficient, but only
      slightly attenuated in Fps/Fes-deficient DRG neurons. CONCLUSION: Fps/Fes and Fer
      are both capable of phosphorylating tubulin and the microtubule regulator CRMP2
      in vitro; and their in vitro kinase activities were both inhibited by CRMP2 or
      PlexinA1, suggesting a possible regulatory interaction. Furthermore, Fer plays a
      more prominent role than Fps/Fes in regulating the axon retraction response to
      Sema3A in DRG neurons. Therefore, Fps/Fes and Fer may play important roles in
      developmental or regenerative axon pathfinding through signaling from Sema3A to
      the microtubule cytoskeleton.

PMID- 18053125
TI  - Restriction landmark genomic scanning (RLGS) spot identification by second
      generation virtual RLGS in multiple genomes with multiple enzyme combinations.
AB  - BACKGROUND: Restriction landmark genomic scanning (RLGS) is one of the most
      successfully applied methods for the identification of aberrant CpG island
      hypermethylation in cancer, as well as the identification of tissue specific
      methylation of CpG islands. However, a limitation to the utility of this method
      has been the ability to assign specific genomic sequences to RLGS spots, a
      process commonly referred to as "RLGS spot cloning." RESULTS: We report the
      development of a virtual RLGS method (vRLGS) that allows for RLGS spot
      identification in any sequenced genome and with any enzyme combination. We report
      significant improvements in predicting DNA fragment migration patterns by
      incorporating sequence information into the migration models, and demonstrate a
      median Euclidian distance between actual and predicted spot migration of 0.18
      centimeters for the most complex human RLGS pattern. We report the confirmed
      identification of 795 human and 530 mouse RLGS spots for the most commonly used
      enzyme combinations. We also developed a method to filter the virtual spots to
      reduce the number of extra spots seen on a virtual profile for both the mouse and
      human genomes. We demonstrate use of this filter to simplify spot cloning and to
      assist in the identification of spots exhibiting tissue-specific methylation.
      CONCLUSION: The new vRLGS system reported here is highly robust for the
      identification of novel RLGS spots. The migration models developed are not
      specific to the genome being studied or the enzyme combination being used, making
      this tool broadly applicable. The identification of hundreds of mouse and human
      RLGS spot loci confirms the strong bias of RLGS studies to focus on CpG islands
      and provides a valuable resource to rapidly study their methylation.

PMID- 18053126
TI  - Immune reconstitution inflammatory syndrome in association with HIV/AIDS and
      tuberculosis: views over hidden possibilities.
AB  - Gut immune components are severely compromised among persons with AIDS, which
      allows increased translocation of bacterial lipopolysaccharides (LPS) into the
      systemic circulation. These microbial LPS are reportedly increased in chronically
      HIV-infected individuals and findings have correlated convincingly with measures
      of immune activation. Immune reconstitution inflammatory syndrome (IRIS) is an
      adverse consequence of the restoration of pathogen-specific immune responses in a
      subset of HIV-infected subjects with underlying latent infections during the
      initial months of highly active antiretroviral treatment (HAART). Whether IRIS is
      the result of a response to a high antigen burden, an excessive response by the
      recovering immune system, exacerbated production of pro-inflammatory cytokines or
      a lack of immune regulation due to inability to produce regulatory cytokines
      remains to be determined. We theorize that those who develop IRIS have a high
      burden of proinflammatory cytokines produced also in response to systemic
      bacterial LPS that nonspecifically act on latent mycobacterial antigens. We also
      hypothesize that subjects that do not develop IRIS could have developed either
      tolerance (anergy) to persistent LPS/tubercle antigens or could have normal
      FOXP3+ gene and that those with defective FOXP3+ gene or those with enormous
      plasma LPS could be vulnerable to IRIS. The measure of microbial LPS, anti-LPS
      antibodies and nonspecific plasma cytokines in subjects on HAART shall predict
      the role of these components in IRIS.

PMID- 18053127
TI  - The establishment and utility of Sweha-Reg: a Swedish population-based registry
      to understand hereditary angioedema.
AB  - BACKGROUND: The importance of acquiring comprehensive epidemiological and
      clinical data on hereditary angioedema has increasingly caught the attention of
      physicians and scientists around the world. The development of networks and
      creation of comprehensive policies to improve care of people suffering from rare
      diseases, such as hereditary angioedema, is a stated top priority of the European
      Union. Hereditary angioedema is a rare disease, that it may be life-threatening.
      Although the exact prevalence is unknown, current estimates suggest that it is
      1/10,000-1/150,000 individuals. The low prevalence requires combined efforts to
      gain accurate epidemiological data on the disease and so give us tools to reduce
      morbidity and mortality, and improve quality of life of sufferers. METHODS: Sweha
      Reg is a population-based registry of hereditary angioedema in Sweden with the
      objectives of providing epidemiological data, and so creates a framework for the
      study of this disease. The registry contains individual-based data on diagnoses,
      treatments and outcomes. CONCLUSION: The present manuscript seeks to raise
      awareness of the existence of Sweha-Reg to stimulate the international
      collaboration of registries. A synthesis of data from similar registries across
      several countries is required to approach an inclusive course understanding of
      HAE.

PMID- 18053128
TI  - An insight into the phylogenetic history of HOX linked gene families in
      vertebrates.
AB  - BACKGROUND: The human chromosomes 2q, 7, 12q and 17q show extensive intra-genomic
      homology, containing duplicate, triplicate and quadruplicate paralogous regions
      centered on the HOX gene clusters. The fact that two or more representatives of
      different gene families are linked with HOX clusters is taken as evidence that
      these paralogous gene sets might have arisen from a single chromosomal segment
      through block or whole chromosome duplication events. This would imply that the
      constituent genes including the HOX clusters reflect the architecture of a single
      ancestral block (before vertebrate origin) where all of these genes were linked
      in a single copy. RESULTS: In the present study we have employed the currently
      available set of protein data for a wide variety of vertebrate and invertebrate
      genomes to analyze the phylogenetic history of 11 multigene families with three
      or more of their representatives linked to human HOX clusters. A topology
      comparison approach revealed four discrete co-duplicated groups: group 1 involves
      the genes from GLI, HH, INHB, IGFBP (cluster-1), and SLC4A families; group 2
      involves ERBB, ZNFN1A, and IGFBP (cluster-2) gene families; group 3 involves the
      HOX clusters and the SP gene family; group 4 involves the integrin beta chain and
      myosine light chain families. The distinct genes within each co-duplicated group
      share the same evolutionary history and are duplicated in concert with each
      other, while the constituent genes of two different co-duplicated groups may not
      share their evolutionary history and may not have duplicated simultaneously.
      CONCLUSION: We conclude that co-duplicated groups may themselves be remnants of
      ancient small-scale duplications (involving chromosomal segments or gene
      clusters) which occurred at different time points during chordate evolution.
      Whereas the recent combination of genes from distinct co-duplicated groups on
      different chromosomal regions (human chromosomes 2q, 7, 12q, and 17q) is probably
      the outcome of subsequent rearrangement of genomic segments, including syntenic
      groups of genes.

PMID- 18053129
TI  - Factors associated with herb and dietary supplement use by young adults in the
      United States.
AB  - BACKGROUND: Little is known about the association between use of herbs and
      dietary supplements (HDS) and lifestyle/behavior factors in young adults in the
      US. METHODS: Analyzing the 2002 National Health Interview Survey (NHIS), we
      examined the patterns of HDS (excluding vitamins/minerals) use among young adults
      in the United States using descriptive statistics and logistic regression.
      RESULTS: In our sample of 18 to 30 year olds (n = 6666), 26% were current
      smokers, 24% were moderate/heavy drinkers, 43% had high physical activity, and
      54% and 76% use prescription and over the counter (OTC) medications respectively.
      Non-vitamin, non-mineral HDS was used by 17% of the overall sample in the last 12
      months. In the multivariable analysis, the lifestyle and behavioral factors
      associated with HDS use include: current smoking (odds ratio 1.41 95% CI [1.16
      1.72]); being a former smoker (1.50 [1.15-1.95]); moderate/heavy alcohol use
      (2.02 [1.53-2.65]); high physical activity levels (2.45 [1.98-3.03]); and
      prescription medication use (1.51 [1.26-1.81]). Among HDS users, only 24%
      discussed their use with a health care professional. CONCLUSION: Nearly one in
      five young adults report using non-vitamin/non-mineral HDS.

PMID- 18053130
TI  - Generating confidence intervals on biological networks.
AB  - BACKGROUND: In the analysis of networks we frequently require the statistical
      significance of some network statistic, such as measures of similarity for the
      properties of interacting nodes. The structure of the network may introduce
      dependencies among the nodes and it will in general be necessary to account for
      these dependencies in the statistical analysis. To this end we require some form
      of Null model of the network: generally rewired replicates of the network are
      generated which preserve only the degree (number of interactions) of each node.
      We show that this can fail to capture important features of network structure,
      and may result in unrealistic significance levels, when potentially confounding
      additional information is available. METHODS: We present a new network resampling
      Null model which takes into account the degree sequence as well as available
      biological annotations. Using gene ontology information as an illustration we
      show how this information can be accounted for in the resampling approach, and
      the impact such information has on the assessment of statistical significance of
      correlations and motif-abundances in the Saccharomyces cerevisiae protein
      interaction network. An algorithm, GOcardShuffle, is introduced to allow for the
      efficient construction of an improved Null model for network data. RESULTS: We
      use the protein interaction network of S. cerevisiae; correlations between the
      evolutionary rates and expression levels of interacting proteins and their
      statistical significance were assessed for Null models which condition on
      different aspects of the available data. The novel GOcardShuffle approach results
      in a Null model for annotated network data which appears better to describe the
      properties of real biological networks. CONCLUSION: An improved statistical
      approach for the statistical analysis of biological network data, which
      conditions on the available biological information, leads to qualitatively
      different results compared to approaches which ignore such annotations. In
      particular we demonstrate the effects of the biological organization of the
      network can be sufficient to explain the observed similarity of interacting
      proteins.

PMID- 18053131
TI  - A new generation of pPRIG-based retroviral vectors.
AB  - BACKGROUND: Retroviral vectors are valuable tools for gene transfer. Particularly
      convenient are IRES-containing retroviral vectors expressing both the protein of
      interest and a marker protein from a single bicistronic mRNA. This coupled
      expression increases the relevance of tracking and/or selection of transduced
      cells based on the detection of a marker protein. pAP2 is a retroviral vector
      containing eGFP downstream of a modified IRES element of EMCV origin, and a CMV
      enhancer-promoter instead of the U3 region of the 5'LTR, which increases its
      efficiency in transient transfection. However, pAP2 contains a limited
      multicloning site (MCS) and shows weak eGFP expression, which previously led us
      to engineer an improved version, termed pPRIG, harboring: i) the wild-type ECMV
      IRES sequence, thereby restoring its full activity; ii) an optimized MCS flanked
      by T7 and SP6 sequences; and iii) a HA tag encoding sequence 5' of the MCS (pPRIG
      HAa/b/c). RESULTS: The convenience of pPRIG makes it a good basic vector to
      generate additional derivatives for an extended range of use. Here we present
      several novel pPRIG-based vectors (collectively referred to as PRIGs) in which :
      i) the HA tag sequence was inserted in the three reading frames 3' of the MCS
      (3'HA PRIGs); ii) a functional domain (ER, VP16 or KRAB) was inserted either 5'
      or 3' of the MCS (<< modular >> PRIGs); iii) eGFP was replaced by either eCFP,
      eYFP, mCherry or puro-R (<< single color/resistance >> PRIGs); and iv) mCherry,
      eYFP or eGFP was inserted 5' of the MCS of the IRES-eGFP, IRES-eCFP or IRES-Puro
      R containing PRIGs, respectively (<< dual color/selection >> PRIGs).
      Additionally, some of these PRIGs were also constructed in a pMigR MSCV
      background which has been widely used in pluripotent cells. CONCLUSION: These
      novel vectors allow for straightforward detection of any expressed protein (3'HA
      PRIGs), for functional studies of chimeric proteins (<< modular >> PRIGs), for
      multiple transductions and fluorescence analyses of transduced cells (<< single
      color/resistance >> PRIGs), or for quantitative detection of studied proteins in
      independently identified/selected transduced cells (<< dual color/selection >>
      PRIGs). They maintain the original advantages of pPRIG and provide suitable tools
      for either transient or stable expression and functional studies in a large range
      of experimental settings.

PMID- 18053132
TI  - Statistical learning of peptide retention behavior in chromatographic
      separations: a new kernel-based approach for computational proteomics.
AB  - BACKGROUND: High-throughput peptide and protein identification technologies have
      benefited tremendously from strategies based on tandem mass spectrometry (MS/MS)
      in combination with database searching algorithms. A major problem with existing
      methods lies within the significant number of false positive and false negative
      annotations. So far, standard algorithms for protein identification do not use
      the information gained from separation processes usually involved in peptide
      analysis, such as retention time information, which are readily available from
      chromatographic separation of the sample. Identification can thus be improved by
      comparing measured retention times to predicted retention times. Current
      prediction models are derived from a set of measured test analytes but they
      usually require large amounts of training data. RESULTS: We introduce a new
      kernel function which can be applied in combination with support vector machines
      to a wide range of computational proteomics problems. We show the performance of
      this new approach by applying it to the prediction of peptide adsorption/elution
      behavior in strong anion-exchange solid-phase extraction (SAX-SPE) and ion-pair
      reversed-phase high-performance liquid chromatography (IP-RP-HPLC). Furthermore,
      the predicted retention times are used to improve spectrum identifications by a p
      value-based filtering approach. The approach was tested on a number of different
      datasets and shows excellent performance while requiring only very small training
      sets (about 40 peptides instead of thousands). Using the retention time predictor
      in our retention time filter improves the fraction of correctly identified
      peptide mass spectra significantly. CONCLUSION: The proposed kernel function is
      well-suited for the prediction of chromatographic separation in computational
      proteomics and requires only a limited amount of training data. The performance
      of this new method is demonstrated by applying it to peptide retention time
      prediction in IP-RP-HPLC and prediction of peptide sample fractionation in SAX
      SPE. Finally, we incorporate the predicted chromatographic behavior in a p-value
      based filter to improve peptide identifications based on liquid chromatography
      tandem mass spectrometry.

PMID- 18053133
TI  - Primary mediastinal liposarcoma: a case report.
AB  - INTRODUCTION: Liposarcoma is the most commonly diagnosed soft tissue sarcoma in
      adults and occurs predominantly in the lower limbs and retroperitoneum. Primary
      mediastinal liposarcomas are rare.They are often asymptomatic and when growing to
      large size the presenting symptoms are related to direct invasion or compression
      of other thoracic organs such as the heart, great vessels and lung. CASE
      PRESENTATION: A case of a 68-year-old man with primary mediastinal liposarcoma
      involving the diaphragm and pericardium and successfully managed by complete
      surgical excision is presented. The patient's postoperative course was uneventful
      with no evidence of recurrence 9 months after the operation. CONCLUSION: Surgical
      removal is the optimal treatment for a mediastinal liposarcoma. If the entire
      tumor can not be resected, surgical debulking often results in symptomatic
      relief. International literature has demonstrated that recurrent disease occurs
      and therefore a long-term careful follow up is required.

PMID- 18053134
TI  - A structural analysis of in vitro catalytic activities of hammerhead ribozymes.
AB  - BACKGROUND: Ribozymes are small catalytic RNAs that possess the dual functions of
      sequence-specific RNA recognition and site-specific cleavage. Trans-cleaving
      ribozymes can inhibit translation of genes at the messenger RNA (mRNA) level in
      both eukaryotic and prokaryotic systems and are thus useful tools for studies of
      gene function. However, identification of target sites for efficient cleavage
      poses a challenge. Here, we have considered a number of structural and
      thermodynamic parameters that can affect the efficiency of target cleavage, in an
      attempt to identify rules for the selection of functional ribozymes. RESULTS: We
      employed the Sfold program for RNA secondary structure prediction, to account for
      the likely population of target structures that co-exist in dynamic equilibrium
      for a specific mRNA molecule. We designed and prepared 15 hammerhead ribozymes to
      target GUC cleavage sites in the mRNA of the breast cancer resistance protein
      (BCRP). These ribozymes were tested, and their catalytic activities were measured
      in vitro. We found that target disruption energy owing to the alteration of the
      local target structure necessary for ribozyme binding, and the total energy
      change of the ribozyme-target hybridization, are two significant parameters for
      prediction of ribozyme activity. Importantly, target disruption energy is the
      major contributor to the predictability of ribozyme activity by the total energy
      change. Furthermore, for a target-site specific ribozyme, incorrect folding of
      the catalytic core, or interactions involving the two binding arms and the end
      sequences of the catalytic core, can have detrimental effects on ribozyme
      activity. CONCLUSION: The findings from this study suggest rules for structure
      based rational design of trans-cleaving hammerhead ribozymes in gene knockdown
      studies. Tools implementing these rules are available from the Sribo module and
      the Srna module of the Sfold program available through Web server at
      http://sfold.wadsworth.org.

PMID- 18053136
TI  - Capacity management of nursing staff as a vehicle for organizational improvement.
AB  - BACKGROUND: Capacity management systems create insight into required resources
      like staff and equipment. For inpatient hospital care, capacity management
      requires information on beds and nursing staff capacity, on a daily as well as
      annual basis. This paper presents a comprehensive capacity model that gives
      insight into required nursing staff capacity and opportunities to improve
      capacity utilization on a ward level. METHODS: A capacity model was developed to
      calculate required nursing staff capacity. The model used historical bed
      utilization, nurse-patient ratios, and parameters concerning contract hours to
      calculate beds and nursing staff needed per shift and the number of nurses needed
      on an annual basis in a ward. The model was applied to three different capacity
      management problems on three separate groups of hospital wards. The problems
      entailed operational, tactical, and strategic management issues: optimizing
      working processes on pediatric wards, predicting the consequences of reducing
      length of stay on nursing staff required on a cardiology ward, and calculating
      the nursing staff consequences of merging two internal medicine wards. RESULTS:
      It was possible to build a model based on easily available data that calculate
      the nursing staff capacity needed daily and annually and that accommodate
      organizational improvements. Organizational improvement processes were initiated
      in three different groups of wards. For two pediatric wards, the most important
      improvements were found to be improving working processes so that the agreed
      nurse-patient ratios could be attained. In the second case, for a cardiology
      ward, what-if analyses with the model showed that workload could be substantially
      lowered by reducing length of stay. The third case demonstrated the possible
      savings in capacity that could be achieved by merging two small internal medicine
      wards. CONCLUSION: A comprehensive capacity model was developed and successfully
      applied to support capacity decisions on operational, tactical, and strategic
      levels. It appeared to be a useful tool for supporting discussions between wards
      and hospital management by giving objective and quantitative insight into staff
      and bed requirements. Moreover, the model was applied to initiate organizational
      improvements, which resulted in more efficient capacity utilization.

PMID- 18053135
TI  - Exosomal transfer of proteins and RNAs at synapses in the nervous system.
AB  - BACKGROUND: Many cell types have been reported to secrete small vesicles called
      exosomes, that are derived from multivesicular bodies and that can also form from
      endocytic-like lipid raft domains of the plasma membrane. Secretory exosomes
      contain a characteristic composition of proteins, and a recent report indicates
      that mast cell exosomes harbor a variety of mRNAs and microRNAs as well. Exosomes
      express cell recognition molecules on their surface that facilitate their
      selective targeting and uptake into recipient cells. RESULTS: In this review, I
      suggest that exosomal secretion of proteins and RNAs may be a fundamental mode of
      communication within the nervous system, supplementing the known mechanisms of
      anterograde and retrograde signaling across synapses. In one specific scenario,
      exosomes are proposed to bud from the lipid raft region of the postsynaptic
      membrane adjacent to the postsynaptic density, in a manner that is stimulated by
      stimuli that elicit long-term potentiation. The exosomes would then transfer
      newly synthesized synaptic proteins (such as CAM kinase II alpha) and synaptic
      RNAs to the presynaptic terminal, where they would contribute to synaptic
      plasticity. CONCLUSION: The model is consistent with the known cellular and
      molecular features of synaptic neurobiology and makes a number of predictions
      that can be tested in vitro and in vivo.

PMID- 18053137
TI  - Scar-like lesion on dorsal nose (cellular neurothekeoma).
AB  - Neurothekeomas are tumors of neural differentiation and of unknown origin that
      occur in females at the 2nd and 3rd decades of life. They usually affect the face
      with an unspecific clinical aspect. The histological features include cellular or
      mixoid differentiation and immunohistochemistry can be positive for protein s
      100, vimentin and epithelilal membrane antigen (EMA). This case report presents a
      13-year-old female patient with nasal neurothekeoma of cellular variety and
      strongly positive for vimentin and s-100; and negative for EMA.

PMID- 18053138
TI  - Environmental adversity and uncertainty favour cooperation.
AB  - BACKGROUND: A major cornerstone of evolutionary biology theory is the explanation
      of the emergence of cooperation in communities of selfish individuals. There is
      an unexplained tendency in the plant and animal world - with examples from alpine
      plants, worms, fish, mole-rats, monkeys and humans - for cooperation to flourish
      where the environment is more adverse (harsher) or more unpredictable. RESULTS:
      Using mathematical arguments and computer simulations we show that in more
      adverse environments individuals perceive their resources to be more
      unpredictable, and that this unpredictability favours cooperation. First we show
      analytically that in a more adverse environment the individual experiences
      greater perceived uncertainty. Second we show through a simulation study that
      more perceived uncertainty implies higher level of cooperation in communities of
      selfish individuals. CONCLUSION: This study captures the essential features of
      the natural examples: the positive impact of resource adversity or uncertainty on
      cooperation. These newly discovered connections between environmental adversity,
      uncertainty and cooperation help to explain the emergence and evolution of
      cooperation in animal and human societies.

PMID- 18053139
TI  - OrthoMaM: a database of orthologous genomic markers for placental mammal
      phylogenetics.
AB  - BACKGROUND: Molecular sequence data have become the standard in modern day
      phylogenetics. In particular, several long-standing questions of mammalian
      evolutionary history have been recently resolved thanks to the use of molecular
      characters. Yet, most studies have focused on only a handful of standard markers.
      The availability of an ever increasing number of whole genome sequences is a
      golden mine for modern systematics. Genomic data now provide the opportunity to
      select new markers that are potentially relevant for further resolving branches
      of the mammalian phylogenetic tree at various taxonomic levels. DESCRIPTION: The
      EnsEMBL database was used to determine a set of orthologous genes from 12
      available complete mammalian genomes. As targets for possible amplification and
      sequencing in additional taxa, more than 3,000 exons of length > 400 bp have been
      selected, among which 118, 368, 608, and 674 are respectively retrieved for 12,
      11, 10, and 9 species. A bioinformatic pipeline has been developed to provide
      evolutionary descriptors for these candidate markers in order to assess their
      potential phylogenetic utility. The resulting OrthoMaM (Orthologous Mammalian
      Markers) database can be queried and alignments can be downloaded through a
      dedicated web interface http://kimura.univ-montp2.fr/orthomam. CONCLUSION: The
      importance of marker choice in phylogenetic studies has long been stressed. Our
      database centered on complete genome information now makes possible to select
      promising markers to a given phylogenetic question or a systematic framework by
      querying a number of evolutionary descriptors. The usefulness of the database is
      illustrated with two biological examples. First, two potentially useful markers
      were identified for rodent systematics based on relevant evolutionary parameters
      and sequenced in additional species. Second, a complete, gapless 94 kb
      supermatrix of 118 orthologous exons was assembled for 12 mammals. Phylogenetic
      analyses using probabilistic methods unambiguously supported the new placental
      phylogeny by retrieving the monophyly of Glires, Euarchontoglires,
      Laurasiatheria, and Boreoeutheria. Muroid rodents thus do not represent a basal
      placental lineage as it was mistakenly reasserted in some recent phylogenomic
      analyses based on fewer taxa. We expect the OrthoMaM database to be useful for
      further resolving the phylogenetic tree of placental mammals and for better
      understanding the evolutionary dynamics of their genomes, i.e., the forces that
      shaped coding sequences in terms of selective constraints.

PMID- 18053140
TI  - Prevalence of anemia and deficiency of iron, folic acid, and zinc in children
      younger than 2 years of age who use the health services provided by the Mexican
      Social Security Institute.
AB  - BACKGROUND: In Mexico, as in other developing countries, micronutrient
      deficiencies are common in infants between 6 and 24 months of age and are an
      important public health problem. The objective of this study was to determine the
      prevalence of anemia and of iron, folic acid, and zinc deficiencies in Mexican
      children under 2 years of age who use the health care services provided by the
      Mexican Institute for Social Security (IMSS). METHODS: A nationwide survey was
      conducted with a representative sample of children younger than 2 years of age,
      beneficiaries, and users of health care services provided by IMSS through its
      regular regimen (located in urban populations) and its Oportunidades program
      (services offered in rural areas). A subsample of 4,955 clinically healthy
      children was studied to determine their micronutrient status. A venous blood
      sample was drawn to determine hemoglobin, serum ferritin, percent of transferrin
      saturation, zinc, and folic acid. Descriptive statistics include point estimates
      and 95% confidence intervals for the sample and projections for the larger
      population from which the sample was drawn. RESULTS: Twenty percent of children
      younger than 2 years of age had anemia, and 27.8% (rural) to 32.6% (urban) had
      iron deficiency; more than 50% of anemia was not associated with low ferritin
      concentrations. Iron stores were more depleted as age increased. Low serum zinc
      and folic acid deficiencies were 28% and 10%, respectively, in the urban areas,
      and 13% and 8%, respectively, in rural areas. The prevalence of simultaneous iron
      and zinc deficiencies was 9.2% and 2.7% in urban and rural areas. Children with
      anemia have higher percentages of folic acid deficiency than children with normal
      iron status. CONCLUSION: Iron and zinc deficiencies constitute the principal
      micronutrient deficiencies in Mexican children younger than 2 years old who use
      the health care services provided by IMSS. Anemia not associated with low
      ferritin values was more prevalent than iron-deficiency anemia. The presence of
      micronutrient deficiencies at this early age calls for effective preventive
      public nutrition programs to address them.

PMID- 18053141
TI  - Detecting groups of coevolving positions in a molecule: a clustering approach.
AB  - BACKGROUND: Although the patterns of co-substitutions in RNA is now well
      characterized, detection of coevolving positions in proteins remains a difficult
      task. It has been recognized that the signal is typically weak, due to the fact
      that (i) amino-acid are characterized by various biochemical properties, so that
      distinct amino acids changes are not functionally equivalent, and (ii) a given
      mutation can be compensated by more than one mutation, at more than one position.
      RESULTS: We present a new method based on phylogenetic substitution mapping. The
      two above-mentioned problems are addressed by (i) the introduction of a weighted
      mapping, which accounts for the biochemical effects (volume, polarity, charge) of
      amino-acid changes, (ii) the use of a clustering approach to detect groups of
      coevolving sites of virtually any size, and (iii) the distinction between
      biochemical compensation and other coevolutionary mechanisms. We apply this
      methodology to a previously studied data set of bacterial ribosomal RNA, and to
      three protein data sets (myoglobin of vertebrates, S-locus Receptor Kinase and
      Methionine Amino-Peptidase). CONCLUSION: We succeed in detecting groups of sites
      which significantly depart the null hypothesis of independence. Group sizes range
      from pairs to groups of size approximately 10, depending on the substitution
      weights used. The structural and functional relevance of these groups of sites
      are assessed, and the various evolutionary processes potentially generating
      correlated substitution patterns are discussed.

PMID- 18053142
TI  - Domain motions of Argonaute, the catalytic engine of RNA interference.
AB  - BACKGROUND: The Argonaute protein is the core component of the RNA-induced
      silencing complex, playing the central role of cleaving the mRNA target. Visual
      inspection of static crystal structures already has enabled researchers to
      suggest conformational changes of Argonaute that might occur during RNA
      interference. We have taken the next step by performing an all-atom normal mode
      analysis of the Pyrococcus furiosus and Aquifex aeolicus Argonaute crystal
      structures, allowing us to quantitatively assess the feasibility of these
      conformational changes. To perform the analysis, we begin with the energy
      minimized X-ray structures. Normal modes are then calculated using an all-atom
      molecular mechanics force field. RESULTS: The analysis reveals low-frequency
      vibrations that facilitate the accommodation of RNA duplexes - an essential step
      in target recognition. The Pyrococcus furiosus and Aquifex aeolicus Argonaute
      proteins both exhibit low-frequency torsion and hinge motions; however,
      differences in the overall architecture of the proteins cause the detailed
      dynamics to be significantly different. CONCLUSION: Overall, low-frequency
      vibrations of Argonaute are consistent with mechanisms within the current
      reaction cycle model for RNA interference.

PMID- 18053143
TI  - Does practicing hatha yoga satisfy recommendations for intensity of physical
      activity which improves and maintains health and cardiovascular fitness?
AB  - BACKGROUND: Little is known about the metabolic and heart rate responses to a
      typical hatha yoga session. The purposes of this study were 1) to determine
      whether a typical yoga practice using various postures meets the current
      recommendations for levels of physical activity required to improve and maintain
      health and cardiovascular fitness; 2) to determine the reliability of metabolic
      costs of yoga across sessions; 3) to compare the metabolic costs of yoga practice
      to those of treadmill walking. METHODS: In this observational study, 20
      intermediate-to-advanced level yoga practitioners, age 31.4 +/- 8.3 years,
      performed an exercise routine inside a human respiratory chamber (indirect
      calorimeter) while wearing heart rate monitors. The exercise routine consisted of
      30 minutes of sitting, 56 minutes of beginner-level hatha yoga administered by
      video, and 10 minutes of treadmill walking at 3.2 and 4.8 kph each. Measures were
      mean oxygen consumption (VO2), heart rate (HR), percentage predicted maximal
      heart rate (%MHR), metabolic equivalents (METs), and energy expenditure (kcal).
      Seven subjects repeated the protocol so that measurement reliability could be
      established. RESULTS: Mean values across the entire yoga session for VO2, HR,
      %MHR, METs, and energy/min were 0.6 L/kg/min; 93.2 beats/min; 49.4%; 2.5; and 3.2
      kcal/min; respectively. Results of the ICCs (2,1) for mean values across the
      entire yoga session for kcal, METs, and %MHR were 0.979 and 0.973, and 0.865,
      respectively. CONCLUSION: Metabolic costs of yoga averaged across the entire
      session represent low levels of physical activity, are similar to walking on a
      treadmill at 3.2 kph, and do not meet recommendations for levels of physical
      activity for improving or maintaining health or cardiovascular fitness. Yoga
      practice incorporating sun salutation postures exceeding the minimum bout of 10
      minutes may contribute some portion of sufficiently intense physical activity to
      improve cardio-respiratory fitness in unfit or sedentary individuals. The
      measurement of energy expenditure across yoga sessions is highly reliable.

PMID- 18053145
TI  - Discovery of novel alternatively spliced C. elegans transcripts by computational
      analysis of SAGE data.
AB  - BACKGROUND: Alternative RNA splicing allows cells to produce multiple protein
      isoforms from one gene. These isoforms may have specialized functions, and may be
      tissue- or stage-specific. Our aim was to use computational analysis of SAGE and
      genomic data to predict alternatively spliced transcripts expressed in C.
      elegans. RESULTS: We predicted novel alternatively spliced variants and confirmed
      five of eighteen candidates selected for experimental validation by RT-PCR tests
      and DNA sequencing. CONCLUSION: We show that SAGE data can be efficiently used to
      discover alternative mRNA isoforms, including those with skipped exons or
      retained introns. Our results also imply that C. elegans may produce a larger
      number of alternatively spliced transcripts than initially estimated.

PMID- 18053144
TI  - Review on solving the forward problem in EEG source analysis.
AB  - BACKGROUND: The aim of electroencephalogram (EEG) source localization is to find
      the brain areas responsible for EEG waves of interest. It consists of solving
      forward and inverse problems. The forward problem is solved by starting from a
      given electrical source and calculating the potentials at the electrodes. These
      evaluations are necessary to solve the inverse problem which is defined as
      finding brain sources which are responsible for the measured potentials at the
      EEG electrodes. METHODS: While other reviews give an extensive summary of the
      both forward and inverse problem, this review article focuses on different
      aspects of solving the forward problem and it is intended for newcomers in this
      research field. RESULTS: It starts with focusing on the generators of the EEG:
      the post-synaptic potentials in the apical dendrites of pyramidal neurons. These
      cells generate an extracellular current which can be modeled by Poisson's
      differential equation, and Neumann and Dirichlet boundary conditions. The
      compartments in which these currents flow can be anisotropic (e.g. skull and
      white matter). In a three-shell spherical head model an analytical expression
      exists to solve the forward problem. During the last two decades researchers have
      tried to solve Poisson's equation in a realistically shaped head model obtained
      from 3D medical images, which requires numerical methods. The following methods
      are compared with each other: the boundary element method (BEM), the finite
      element method (FEM) and the finite difference method (FDM). In the last two
      methods anisotropic conducting compartments can conveniently be introduced. Then
      the focus will be set on the use of reciprocity in EEG source localization. It is
      introduced to speed up the forward calculations which are here performed for each
      electrode position rather than for each dipole position. Solving Poisson's
      equation utilizing FEM and FDM corresponds to solving a large sparse linear
      system. Iterative methods are required to solve these sparse linear systems. The
      following iterative methods are discussed: successive over-relaxation, conjugate
      gradients method and algebraic multigrid method. CONCLUSION: Solving the forward
      problem has been well documented in the past decades. In the past simplified
      spherical head models are used, whereas nowadays a combination of imaging
      modalities are used to accurately describe the geometry of the head model.
      Efforts have been done on realistically describing the shape of the head model,
      as well as the heterogenity of the tissue types and realistically determining the
      conductivity. However, the determination and validation of the in vivo
      conductivity values is still an important topic in this field. In addition, more
      studies have to be done on the influence of all the parameters of the head model
      and of the numerical techniques on the solution of the forward problem.

PMID- 18053146
TI  - The oncoprotein H-RasV12 increases mitochondrial metabolism.
AB  - BACKGROUND: Neoplastic cells increase glycolysis in order to produce anabolic
      precursors and energy within the hypoxic environment of a tumor. Ras signaling is
      activated in several cancers and has been found to regulate metabolism by
      enhancing glycolytic flux to lactate. We examined the effects of sequential
      immortalization and H-RasV12-transformation of human bronchial epithelial cells
      on the anabolic fate of fully-labeled 13C-glucose-derived carbons using two
      dimensional total correlated spectroscopic analysis-nuclear magnetic resonance
      spectroscopy (2D TOCSY-NMR). RESULTS: We found that the introduction of activated
      H-RasV12 into immortalized human bronchial epithelial cells unexpectedly
      increased tricarboxylic acid cycle activity as measured by the direct conversion
      of 13C-glucose carbons into the anabolic substrates glutamate/glutamine,
      aspartate and uridine. We then observed that immortalization and H-RasV12
      transformation of bronchial epithelial cells caused a stepwise increase in oxygen
      consumption, a global measure of electron transport chain activity. Importantly,
      ectopic expression of H-RasV12 sensitized immortalized cells to the ATP-depleting
      and cytotoxic effects of electron transport perturbation using the complex I
      inhibitor rotenone. CONCLUSION: Taken together, these data indicate that the
      oncoprotein H-RasV12 increases mitochondrial metabolism and provide new rationale
      for the targeting of the tricarboxylic acid cycle and electron transport chain as
      anti-neoplastic strategies.

PMID- 18053147
TI  - Understanding animal fears: a comparison of the cognitive vulnerability and harm
      looming models.
AB  - BACKGROUND: The Cognitive Vulnerability Model holds that both clinical and sub
      clinical manifestations of animal fears are a result of how an animal is
      perceived, and can be used to explain both individual differences in fear
      acquisition and the uneven distribution of fears in the population. This study
      looked at the association between fear of a number of animals and perceptions of
      the animals as uncontrollable, unpredictable, dangerous and disgusting. Also
      assessed were the perceived loomingness, prior familiarity, and negative
      evaluation of the animals as well as possible conditioning experiences. METHODS:
      162 first-year University students rated their fear and perceptions of four high
      fear and four low-fear animals. RESULTS: Perceptions of the animals as dangerous,
      disgusting and uncontrollable were significantly associated with fear of both
      high- and low-fear animals while perceptions of unpredictability were
      significantly associated with fear of high-fear animals. Conditioning experiences
      were unrelated to fear of any animals. In multiple regression analyses,
      loomingness did not account for a significant amount of the variance in fear
      beyond that accounted for by the cognitive vulnerability variables. However, the
      vulnerability variables accounted for between 20% and 51% of the variance in all
      animals fears beyond that accounted for by perceptions of the animals as looming.
      Perceptions of dangerousness, uncontrollability and unpredictability were highly
      predictive of the uneven distribution of animal fears. CONCLUSION: This study
      provides support for the Cognitive Vulnerability Model of the etiology of
      specific fears and phobias and brings into question the utility of the harm
      looming model in explaining animal fear.

PMID- 18053148
TI  - Chlorin e6 - polyvinylpyrrolidone mediated photosensitization is effective
      against human non-small cell lung carcinoma compared to small cell lung carcinoma
      xenografts.
AB  - BACKGROUND: Photodynamic therapy (PDT) is an effective local cancer treatment
      that involves light activation of a photosensitizer, resulting in oxygen
      dependent, free radical-mediated cell death. Little is known about the
      comparative efficacy of PDT in treating non-small cell lung carcinoma (NSCLC) and
      small cell lung carcinoma (SCLC), despite ongoing clinical trials treating lung
      cancers. The present study evaluated the potential use of chlorin e6 -
      polyvinylpyrrolidone (Ce6-PVP) as a multimodality photosensitizer for
      fluorescence detection and photodynamic therapy (PDT) on NSCLC and SCLC
      xenografts. RESULTS: Human NSCLC (NCI-H460) and SCLC (NCI-H526) tumor cell lines
      were used to establish tumor xenografts in the chick chorioallantoic membrane
      (CAM) model as well as in the Balb/c nude mice. In the CAM model, Ce6-PVP was
      applied topically (1.0 mg/kg) and fluorescence intensity was charted at various
      time points. Tumor-bearing mice were given intravenous administration of Ce6-PVP
      (2.0 mg/kg) and laser irradiation at 665 nm (fluence of 150 J/cm2 and fluence
      rate of 125 mW/cm2). Tumor response was evaluated at 48 h post PDT. Studies of
      temporal fluorescence pharmacokinetics in CAM tumor xenografts showed that Ce6
      PVP has a selective localization and a good accuracy in demarcating NSCLC
      compared to SCLC from normal surrounding CAM after 3 h post drug administration.
      Irradiation at 3 h drug-light interval showed greater tumor necrosis against
      human NSCLC xenografts in nude mice. SCLC xenografts were observed to express
      resistance to photosensitization with Ce6-PVP. CONCLUSION: The formulation of Ce6
      PVP is distinctly advantageous as a diagnostic and therapeutic agent for
      fluorescence diagnosis and PDT of NSCLC.

PMID- 18053150
TI  - World AIDS Day 2007: AIDS at 26, are we there yet?
AB  - This editorial comments on selected progress made in combating the acquired
      immune deficiency syndrome (AIDS) after 26 years and some of the remaining
      challenges.

PMID- 18053149
TI  - A comprehensive analysis of common genetic variation in prolactin (PRL) and PRL
      receptor (PRLR) genes in relation to plasma prolactin levels and breast cancer
      risk: the multiethnic cohort.
AB  - BACKGROUND: Studies in animals and humans clearly indicate a role for prolactin
      (PRL) in breast epithelial proliferation, differentiation, and tumorigenesis.
      Prospective epidemiological studies have also shown that women with higher
      circulating PRL levels have an increase in risk of breast cancer, suggesting that
      variability in PRL may also be important in determining a woman's risk. METHODS:
      We evaluated genetic variation in the PRL and PRL receptor (PRLR) genes as
      predictors of plasma PRL levels and breast cancer risk among African-American,
      Native Hawaiian, Japanese-American, Latina, and White women in the Multiethnic
      Cohort Study (MEC). We selected single nucleotide polymorphisms (SNPs) from both
      the public (dbSNP) and private (Celera) databases to construct high density SNP
      maps that included up to 20 kilobases (kb) upstream of the transcription
      initiation site and 10 kb downstream of the last exon of each gene, for a total
      coverage of 59 kb in PRL and 210 kb in PRLR. We genotyped 80 SNPs in PRL and 173
      SNPs in PRLR in a multiethnic panel of 349 unaffected subjects to characterize
      linkage disequilibrium (LD) and haplotype patterns. We sequenced the coding
      regions of PRL and PRLR in 95 advanced breast cancer cases (19 of each
      racial/ethnic group) to uncover putative functional variation. A total of 33 and
      60 haplotype "tag" SNPs (tagSNPs) that allowed for high predictability (Rh2 > or
      = 0.70) of the common haplotypes in PRL and PRLR, respectively, were then
      genotyped in a multiethnic breast cancer case-control study of 1,615 invasive
      breast cancer cases and 1,962 controls in the MEC. We also assessed the
      association of common genetic variation with circulating PRL levels in 362
      postmenopausal controls without a history of hormone therapy use at blood draw.
      Because of the large number of comparisons being performed we used a relatively
      stringent type I error criteria (p < 0.0005) for evaluating the significance of
      any single association to correct for performing approximately 100 independent
      tests, close to the number of tagSNPs genotyped for both genes. RESULTS: We
      observed no significant associations between PRL and PRLR haplotypes or
      individual SNPs in relation to breast cancer risk. A nominally significant
      association was noted between prolactin levels and a tagSNP (tagSNP 44,
      rs2244502) in intron 1 of PRL. This SNP showed approximately a 50% increase in
      levels between minor allele homozygotes vs. major allele homozygotes. However,
      this association was not significant (p = 0.002) using our type I error criteria
      to correct for multiple testing, nor was this SNP associated with breast cancer
      risk (p = 0.58). CONCLUSION: In this comprehensive analysis covering 59 kb of the
      PRL locus and 210 kb of the PRLR locus, we found no significant association
      between common variation in these candidate genes and breast cancer risk or
      plasma PRL levels. The LD characterization of PRL and PRLR in this multiethnic
      population provide a framework for studying these genes in relation to other
      disease outcomes that have been associated with PRL, as well as for larger
      studies of plasma PRL levels.

PMID- 18053151
TI  - Localised pericardial tamponade diagnosed by computed tomography: a case
      presentation.

PMID- 18053152
TI  - Nanotechnology-based drug delivery systems.
AB  - Nanoparticles hold tremendous potential as an effective drug delivery system. In
      this review we discussed recent developments in nanotechnology for drug delivery.
      To overcome the problems of gene and drug delivery, nanotechnology has gained
      interest in recent years. Nanosystems with different compositions and biological
      properties have been extensively investigated for drug and gene delivery
      applications. To achieve efficient drug delivery it is important to understand
      the interactions of nanomaterials with the biological environment, targeting cell
      surface receptors, drug release, multiple drug administration, stability of
      therapeutic agents and molecular mechanisms of cell signalling involved in
      pathobiology of the disease under consideration. Several anti-cancer drugs
      including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been
      successfully formulated using nanomaterials. Quantom dots, chitosan,
      Polylactic/glycolic acid (PLGA) and PLGA-based nanoparticles have also been used
      for in vitro RNAi delivery. Brain cancer is one of the most difficult
      malignancies to detect and treat mainly because of the difficulty in getting
      imaging and therapeutic agents past the blood-brain barrier and into the brain.
      Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have
      been shown to cross the intact blood-brain barrier and released at therapeutic
      concentrations in the brain. The use of nanomaterials including peptide-based
      nanotubes to target the vascular endothelial growth factor (VEGF) receptor and
      cell adhesion molecules like integrins, cadherins and selectins, is a new
      approach to control disease progression.

PMID- 18053153
TI  - The results of arthroscopic versus mini-open repair for rotator cuff tears at mid
      term follow-up.
AB  - BACKGROUND: To prospectively evaluate patients who underwent a "mini-open" repair
      versus a completely arthroscopic technique for small to large size rotator cuff
      tears. METHODS: Fifty-two patients underwent "mini-open" or all arthroscopic
      repair of a full thickness tear of the rotator cuff. Patients who complained of
      shoulder pain and/or weakness and who had failed a minimum of 6 weeks of physical
      therapy and had at least one sub-acromial injection were surgical candidates. Pre
      and post-operative clinical evaluations included the following: 1) demographics;
      2) Simple Shoulder Test (SST); 3) University of California, Los Angeles (UCLA)
      rating scale; 4) visual analog pain assessment (VAS); and 5) pre-op SF12
      assessment. Descriptive analysis was performed for patient demographics and for
      all variables. Pre and post outcome scores, range of motion and pain scale were
      compared using paired t-tests. Analysis of variance (ANOVA) was used to evaluate
      any effect between dependent and independent variables. Significance was set at p
      is less than or equal to 0.05. RESULTS: There were 31 females and 21 males. The
      average follow-up was 50.6 months (27 - 84 months). The average age was similar
      between the two groups [arthroscopic x = 55 years/mini-open x = 58 years, p =
      0.7]. Twenty-seven patients underwent arthroscopic repair and 25 underwent repair
      with a mini-open incision. The average rotator cuff tear size was 3.1 cm (range:
      1-5 centimeters). There was no significant difference in tear size between the
      two groups (arthroscopic group = 2.9 cm/mini-open group = 3.2 cm, p = 0.3).
      Overall, there was a significant improvement from pre-operative status in
      shoulder pain, shoulder function as measured on the Simple Shoulder test and UCLA
      Shoulder Form. Visual analog pain improved, on average, 4.4 points and the most
      recent Short Shoulder Form and UCLA scores were 8 and 26 respectively. Both
      active and passive glenohumeral joint range of motion improved significantly from
      pre-operatively. CONCLUSION: Based upon the number available, we found no
      statistical difference in outcome between the two groups, indicating that either
      procedure is efficacious in the treatment of small and medium size rotator cuff
      tears. LEVEL OF EVIDENCE: Type III.

PMID- 18053154
TI  - Postoperative phlegmasia caerulea dolens: a case report and consideration of
      potential iatrogenic factors.
AB  - While the haemorrhagic consequences of anti-coagulants are well and frequently
      described in the surgical literature, the paradoxical prothrombotic tendencies of
      these drugs tend to be under-recognised due, perhaps, to their clinical
      infrequency. However, when these effects pertain, their consequences can be
      devastating. Here, we present a postoperative oncology patient who suffered a
      massive recrudescence of his lower limb venous thrombosis immediately after
      discontinuation of his heparin infusion, despite seemingly being adequately
      anticoagulated by warfarin therapy (INR > 2.0). We intend this case to
      graphically illustrate the theoretical considerations that must govern the
      perioperative use of these drugs in high-risk patients.

PMID- 18053156
TI  - An observational study of the effectiveness of practice guideline implementation
      strategies examined according to physicians' cognitive styles.
AB  - BACKGROUND: Reviews of guideline implementation recommend matching strategies to
      the specific setting, but provide little specific guidance about how to do so. We
      hypothesized that the highest level of guideline-concordant care would be
      achieved where implementation strategies fit well with physicians' cognitive
      styles. METHODS: We conducted an observational study of the implementation of
      guidelines for hypertension management among patients with diabetes at 43
      Veterans' Health Administration medical center primary care clinics. Clinic
      leaders provided information about all implementation strategies employed at
      their sites. Guidelines implementation strategies were classified as education,
      motivation/incentive, or barrier reduction using a pre-specified system.
      Physician's cognitive styles were measured on three scales: evidence vs.
      experience as the basis of knowledge, sensitivity to pragmatic concerns, and
      conformity to local practices. Doctors' decisions were designated guideline
      concordant if the patient's blood pressure was within goal range, or if the blood
      pressure was out of range and a dose change or medication change was initiated,
      or if the patient was already using medications from three classes. RESULTS: The
      final sample included 163 physicians and 1,174 patients. All of the participating
      sites used one or more educational approaches to implement the guidelines. Over
      90% of the sites also provided group or individual feedback on physician
      performance on the guidelines, and over 75% implemented some type of reminder
      system. A minority of sites used monetary incentives, penalties, or barrier
      reduction. The only type of intervention that was associated with increased
      guideline-concordant care in a logistic model was barrier reduction (p < 0.02).
      The interaction between physicians' conformity scale scores and the effect of
      barrier reduction was significant (p < 0.05); physicians ranking lower on the
      conformity scale responded more to barrier reduction. CONCLUSION: Guidelines
      implementation strategies that were designed to reduce physician time pressure
      and task complexity were the only ones that improved performance. Education may
      have been necessary but was clearly not sufficient, and more was not better.
      Incentives had no discernible effect. Measurable physician characteristics
      strongly affected response to implementation strategies.

PMID- 18053155
TI  - Requirement of extracellular signal-regulated kinase/mitogen-activated protein
      kinase for long-term potentiation in adult mouse anterior cingulate cortex.
AB  - Long-term potentiation (LTP) in the anterior cingulate cortex (ACC) is believed
      to be critical for higher brain functions including emotion, learning, memory and
      chronic pain. N-methyl-D-aspartate (NMDA) receptor-dependent LTP is well studied
      and is thought to be important for learning and memory in mammalian brains. As
      the downstream target of NMDA receptors, the extracellular signal-regulated
      kinase (ERK) in the mitogen-activated protein kinase (MAPK) cascade has been
      extensively studied for its involvement in synaptic plasticity, learning and
      memory in hippocampus. By contrast, the role of ERK in cingulate LTP has not been
      investigated. In this study, we examined whether LTP in ACC requires the
      activation of ERK. We found that P42/P44 MAPK inhibitors, PD98059 and U0126,
      suppressed the induction of cingulate LTP that was induced by presynaptic
      stimulation with postsynaptic depolarization (the pairing protocol). We also
      showed that cingulate LTP induced by two other different protocols was also
      blocked by PD98059. Moreover, we found that these two inhibitors had no effect on
      the maintenance of cingulate LTP. Inhibitors of c-Jun N-terminal kinase (JNK) and
      p38, other members of MAPK family, SP600125 and SB203850, suppressed the
      induction of cingulate LTP generated by the pairing protocol. Thus, our study
      suggests that the MAPK signaling pathway is involved in the induction of
      cingulate LTP and plays a critical role in physiological conditions.

PMID- 18053157
TI  - Impacts of chronic kidney disease and albuminuria on associations between
      coronary heart disease and its traditional risk factors in type 2 diabetic
      patients - the Hong Kong diabetes registry.
AB  - BACKGROUND: Glycated haemoglobin (HbA1c), blood pressure and body mass index
      (BMI) are risk factors for albuminuria, the latter in turn can lead to
      hyperlipidaemia. We used novel statistical analyses to examine how albuminuria
      and chronic kidney disease (CKD) may influence the effects of other risk factors
      on coronary heart disease (CHD). METHODS: A prospective cohort of 7067 Chinese
      type 2 diabetic patients without history of CHD enrolled since 1995 were censored
      on July 30th, 2005. Cox proportional hazard regression with restricted cubic
      spline was used to auto-select predictors. Hazard ratio plots were used to
      examine the risk of CHD. Based on these plots, non-linear risk factors were
      categorised and the categorised variables were refitted into various Cox models
      in a stepwise manner to confirm the findings. RESULTS: Age, male gender, duration
      of diabetes, spot urinary albumin: creatinine ratio, estimated glomerular
      filtration rate, total cholesterol (TC), high density lipoprotein cholesterol
      (HDL-C) and current smoking status were risk factors of CHD. Linear association
      between TC and CHD was observed only in patients with albuminuria. Although in
      general, increased HDL-C was associated with decreased risk of CHD, full-range
      HDL-C was associated with CHD in an A-shaped manner with a zenith at 1.1 mmol/L.
      Albuminuria and CKD were the main contributors for the paradoxically positive
      association between HDL-C and CHD for HDL-C values less than 1.1 mmol/L.
      CONCLUSION: In type 2 diabetes, albuminuria plays a linking role between
      conventional risk factors and CHD. The onset of CKD changes risk associations
      between lipids and CHD.

PMID- 18053158
TI  - Malaria control in Malawi: are the poor being served?
AB  - BACKGROUND: In Africa, national governments and international organizations are
      focusing on rapidly "scaling up" malaria control interventions to at least 60
      percent of vulnerable populations. The potential health and economic benefits of
      "scaling up" will depend on the equitable access to malaria control measures by
      the poor. This paper analyses the present inequalities in access to malaria
      interventions in Malawi. METHODS: Equity in access to malaria control measures
      was assessed using the Malawi Demographic Health Survey (DHS) 2000 and the 2004
      national survey on malaria control. Utilisation of malaria control methods was
      compared across the wealth quintiles, to determine whether the poor were being
      reached with malaria control measures. RESULTS: Overall ITN coverage increased
      from 5% in 2000 to 35% in 2004. However, there was a disproportionate
      concentration of ITNs amongst the least poor compared to the poorest group.
      Effective treatment of fever remains unacceptably low with only 17% of the under
      five children being promptly treated with an effective antimalarial drug. And
      only 29 percent of pregnant women received the recommended dose of at least two
      doses during the pregnancy. No income related inequalities were associated with
      prompt treatment and IPT use. CONCLUSION: The present distribution strategies for
      ITNs are not addressing the needs of the vulnerable groups, especially the poor.
      Increasing access to ITNs by the poor will require innovative distribution models
      which deliberately target the poorest of the poor.

PMID- 18053159
TI  - Native cardiac reserve predicts survival in acute post infarction heart failure
      in mice.
AB  - Cardiac reserve can be used to predict survival and outcome in patients with
      heart failure. The aim of this study was to investigate if native cardiac reserve
      could predict survival after myocardial infarction (MI) in mice. METHOD: We
      investigated 27 healthy C57Bl6 mice (male symbol10-12 weeks old) with
      echocardiography using a high-frequency 15-MHz linear transducer. Investigations
      were performed both at rest and after pharmacological stress induced by
      dobutamine (1 mug/g body weight i.p.). The day after the echocardiography
      examination, a large MI was induced by ligation of the left anterior descending
      (LAD) coronary artery for evaluation of mortality rate. RESULTS: Two weeks after
      induction of MI, 7 mice were alive (26%). Evaluation of the difference between
      the surviving and deceased animals showed that the survivors had a better native
      ability to increase systolic performance (DeltaLVESd -1.86 vs -1.28mm p = 0.02)
      upon dobutamine challenge, resulting in a better cardiac reserve (DeltaFS 37 vs
      25% p = 0.02 and DeltaCO 0.27 vs -0.10 ml/min p = 0.02) and a better chronotropic
      reserve (DeltaR-R interval -68 vs -19 ms p < 0.01). A positive relationship was
      found between ability to survive and both cardiac (p < 0.05) and chronotropic
      reserve (p < 0.05) when the mice were divided into three groups: survivors,
      surviving < 7 days, and surviving < 1 day. CONCLUSION: We conclude that before MI
      induction the surviving animals had a better cardiac function compared with the
      deceased. This indicates that native cardiac and chronotropic reserve may be an
      important determinant and predictor of survival in the setting of large MI and
      post-infarction heart failure.

PMID- 18053160
TI  - Predicting and improving the protein sequence alignment quality by support vector
      regression.
AB  - BACKGROUND: For successful protein structure prediction by comparative modeling,
      in addition to identifying a good template protein with known structure,
      obtaining an accurate sequence alignment between a query protein and a template
      protein is critical. It has been known that the alignment accuracy can vary
      significantly depending on our choice of various alignment parameters such as gap
      opening penalty and gap extension penalty. Because the accuracy of sequence
      alignment is typically measured by comparing it with its corresponding structure
      alignment, there is no good way of evaluating alignment accuracy without knowing
      the structure of a query protein, which is obviously not available at the time of
      structure prediction. Moreover, there is no universal alignment parameter option
      that would always yield the optimal alignment. RESULTS: In this work, we develop
      a method to predict the quality of the alignment between a query and a template.
      We train the support vector regression (SVR) models to predict the MaxSub scores
      as a measure of alignment quality. The alignment between a query protein and a
      template of length n is transformed into a (n + 1)-dimensional feature vector,
      then it is used as an input to predict the alignment quality by the trained SVR
      model. Performance of our work is evaluated by various measures including Pearson
      correlation coefficient between the observed and predicted MaxSub scores. Result
      shows high correlation coefficient of 0.945. For a pair of query and template, 48
      alignments are generated by changing alignment options. Trained SVR models are
      then applied to predict the MaxSub scores of those and to select the best
      alignment option which is chosen specifically to the query-template pair. This
      adaptive selection procedure results in 7.4% improvement of MaxSub scores,
      compared to those when the single best parameter option is used for all query
      template pairs. CONCLUSION: The present work demonstrates that the alignment
      quality can be predicted with reasonable accuracy. Our method is useful not only
      for selecting the optimal alignment parameters for a chosen template based on
      predicted alignment quality, but also for filtering out problematic templates
      that are not suitable for structure prediction due to poor alignment accuracy.
      This is implemented as a part in FORECAST, the server for fold-recognition and is
      freely available on the web at http://pbil.kaist.ac.kr/forecast.

PMID- 18053161
TI  - Tissue factor pathway inhibitor-2 was repressed by CpG hypermethylation through
      inhibition of KLF6 binding in highly invasive breast cancer cells.
AB  - BACKGROUND: Tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated
      Kunitz inhibitor that inhibits plasmin and trypsin-mediated activation of zymogen
      matrix metalloproteinases involved in tumor progression, invasion and metastasis.
      Here, we have investigated the mechanism of DNA methylation on the repression of
      TFPI-2 in breast cancer cell lines. RESULTS: We found that both protein and mRNA
      of TFPI-2 could not be detected in highly invasive breast cancer cell line MDA-MB
      435. To further investigate the mechanism of TFPI-2 repression in breast cancer
      cells, 1.5 Kb TFPI-2 promoter was cloned, and several genetic variations were
      detected, but the promoter luciferase activities were not affected by the point
      mutation in the promoter region and the phenomena was further supported by
      deleted mutation. Scan mutation and informatics analysis identified a potential
      KLF6 binding site in TFPI-2 promoter. It was revealed, by bisulfite modified
      sequence, that the CpG island in TFPI-2 promoter region was hypermethylated in
      MDA-MB-435. Finally, using EMSA and ChIP assay, we demonstrated that the CpG
      methylation in the binding site of KLF-6 diminished the binding of KLF6 to TFPI-2
      promoter. CONCLUSION: In this study, we found that the CpG islands in TFPI-2
      promoter was hypermethylated in highly invasive breast cancer cell line, and DNA
      methylation in the entire promoter region caused TFPI-2 repression by inducing
      inactive chromatin structure and decreasing KLF6 binding to its DNA binding
      sequence.

PMID- 18053162
TI  - Determination of suitable housekeeping genes for normalisation of quantitative
      real time PCR analysis of cells infected with human immunodeficiency virus and
      herpes viruses.
AB  - The choice of an appropriate housekeeping gene for normalisation purposes has now
      become an essential requirement when designing QPCR experiments. This is of
      particular importance when using QPCR to measure viral and cellular gene
      transcription levels in the context of viral infections as viruses can
      significantly interfere with host cell pathways, the components of which
      traditional housekeeping genes often encode. In this study we have determined the
      reliability of 10 housekeeping genes in context of four heavily studied viral
      infections; human immunodeficiency virus type 1, herpes simplex virus type 1,
      cytomegalovirus and varicella zoster virus infections using a variety of cell
      types and virus strains. This provides researchers of these viruses with a
      shortlist of potential housekeeping genes to use as normalisers for QPCR
      experiments.

PMID- 18053163
TI  - Functional annotation of 19,841 Populus nigra full-length enriched cDNA clones.
AB  - BACKGROUND: Populus is one of favorable model plants because of its small genome.
      Structural genomics of Populus has reached a breakpoint as nucleotides of the
      entire genome have been determined. Reaching the post genome era, functional
      genomics of Populus is getting more important for well-comprehended plant
      science. Development of bioresorce serving functional genomics is making rapid
      progress. Huge efforts have achieved deposits of expressed sequence tags (ESTs)
      in various plant species consequently accelerating functional analysis of genes.
      ESTs from full-length cDNA clones are especially powerful for accurate molecular
      annotation. We promoted collection and annotation of the ESTs from Populus full
      length enriched cDNA clones as part of functional genomics of tree species.
      RESULTS: We have been collecting the full-length enriched cDNA of the female
      poplar (Populus nigra var. italica) for years. By sequencing P. nigra full-length
      (PnFL) cDNA libraries, we generated about 116,000 5'-end or 3'-end ESTs
      corresponding to 19,841 nonredundant PnFL clones. Population of PnFL cDNA clones
      represents 44% of the predicted genes in the Populus genome. CONCLUSION: Our
      resource of P. nigra full-length enriched clones is expected to provide valuable
      tools to gain further insight into genome annotation and functional genomics in
      Populus.

PMID- 18053164
TI  - The proinflammatory cytokines IL-2, IL-15 and IL-21 modulate the repertoire of
      mature human natural killer cell receptors.
AB  - Natural killer (NK) cells play a crucial role in the immune response to micro
      organisms and tumours. Recent evidence suggests that NK cells also regulate the
      adaptive T-cell response and that it might be possible to exploit this ability to
      eliminate autoreactive T cells in autoimmune disease and alloreactive T cells in
      transplantation. Mature NK cells consist of a highly diverse population of cells
      that expresses different receptors to facilitate recognition of diseased cells
      and possibly pathogens themselves. Ex vivo culture of NK cells with cytokines
      such as IL-2 and IL-15 is an approach that permits significant expansion of the
      NK cell subpopulations, which are likely to have potent antitumour, antiviral, or
      immunomodulatory effects in autoimmunity. Our data indicate that the addition of
      IL-21 has a synergistic effect by increasing the numbers of NK cells on a large
      scale. IL-2 and IL-15 may induce the expression of killer cell immunoglobulin
      like receptors (KIRs) in KIR-negative populations, the c-lectin receptor NKG2D
      and the natural cytotoxic receptor NKp44. The addition of IL-21 to IL-15 or IL-2
      can modify the pattern of the KIR receptors and inhibit NKp44 expression by
      reducing the expression of the adaptor DAP-12. IL-21 also preserved the
      production of interferon-gamma and enhanced the cytotoxic properties of NK cells.
      Our findings indicate that the proinflammatory cytokines IL-2, IL-15 and IL-21
      can modify the peripheral repertoire of NK cells. These properties may be used to
      endow subpopulations of NK cells with specific phenotypes, which may be used in
      ex vivo cellular immunotherapy strategies.

PMID- 18053165
TI  - Epidemiology and psycho-social aspects of onchocercal skin diseases in
      northeastern Nigeria.
AB  - BACKGROUND: Observations were made on the prevalence of onchocerciasis and
      Onchocercal Skin Diseases (OSD); frequency of occurrence and anatomical
      distribution of OSD in the Hawal River Valley, an established onchocerciasis
      endemic focus in north-eastern Nigeria. METHODS: Symptoms of OSD were diagnosed
      in 5 844 subjects using Rapid Assessment Method (RAM) while 1 479 of the subjects
      chosen from alternate households had their skin biopsies examined for active
      microfilariae of Onchocerca volvulus. Also, Focal Group Discussions (FGD) were
      conducted at the Health District levels. RESULTS: O. volvulus was recorded in
      (19.0%) and OSD in (43.8%) of the subjects. The Mantel-Haenszel test for linear
      association showed a close agreement between onchocerciasis prevalence and the
      rate of OSD (chi2 = 3.93; p < 0.05). The various forms of OSD occurred in the
      order: CPOD (17.7%), APOD (9.9%), DPM (9.0%), LOD (7.0%) and ATR (3.1%). The
      overall frequency of occurrence of various symptoms of OSD on different
      anatomical locations showed the locations in descending order of occurrence as
      lower limbs (24.6%), upper limbs (21.3%), buttocks (19.9%), shoulder & neck
      (19.1%), abdomen and trunk (11.3%), backside (10.6), and 'other' sites (7.5%).
      The Focal Group Discussion (FGD) revealed the most worrisome consequences of OSD
      as social isolation of victims (31.3%), shame and low self esteem (22.7%) and
      high cost of medication (15.6%). CONCLUSION: It is recommended that
      Onchocerciasis control programmes in the Hawal River Valley and any other focus
      with high incidence of OSD should incorporate an aspect that would address the
      anxiety and depression caused by various OSD lesions since they carry lots of
      psycho-social implications. This would increase acceptance and compliance of the
      target population. The classification criteria of onchocerciasis endemicity
      should be based on either or both of the O. volvulus and onchocercal skin disease
      burden of any community and no longer on O. volvulus parasitic infection rate
      alone.

PMID- 18053166
TI  - Spatial targeted vector control in the highlands of Burundi and its impact on
      malaria transmission.
AB  - BACKGROUND: Prevention of malaria epidemics is a priority for African countries.
      The 2000 malaria epidemic in Burundi prompted the government to implement
      measures for preventing future outbreaks. Case management with artemisinin-based
      combination therapy and malaria surveillance were nationally improved. A vector
      control programme was initiated in one of the most affected highland provinces.
      The focal distribution of malaria vectors in the highlands was the starting point
      for designing a targeted vector control strategy. The objective of this study was
      to present the results of this strategy on malaria transmission in an African
      highland region. METHODS: In Karuzi, in 2002-2005, vector control activities
      combining indoor residual spraying and long-lasting insecticidal nets were
      implemented. The interventions were done before the expected malaria transmission
      period and targeted the valleys between hills, with the expectation that this
      would also protect the populations living at higher altitudes. The impact on the
      Anopheles population and on malaria transmission was determined by nine cross
      sectional surveys carried out at regular intervals throughout the study period.
      RESULTS: Anopheles gambiae s.l. and Anopheles funestus represented 95% of the
      collected anopheline species. In the valleys, where the vector control activities
      were implemented, Anopheles density was reduced by 82% (95% CI: 69-90).
      Similarly, transmission was decreased by 90% (95% CI: 63%-97%, p = 0.001). In the
      sprayed valleys, Anopheles density was further reduced by 79.5% (95% CI: 51.7
      91.3, p < 0.001) in the houses with nets as compared to houses without them. No
      significant impact on vector density and malaria transmission was observed in the
      hill tops. However, the intervention focused on the high risk areas near the
      valley floor, where 93% of the vectors are found and 90% of the transmission
      occurs. CONCLUSION: Spatial targeted vector control effectively reduced Anopheles
      density and transmission in this highland district. Bed nets have an additional
      effect on Anopheles density though this did not translate in an additional impact
      on transmission. Though no impact was observed in the hilltops, the programme
      successfully covered the areas most at risk. Such a targeted strategy could
      prevent the emergence and spread of an epidemic from these high risk foci.

PMID- 18053167
TI  - Hypercalcemia after transplant nephrectomy in a hemodialysis patient: a case
      report.
AB  - INTRODUCTION: Hypercalcemia is a complication often seen in chronic hemodialysis
      patients. A rare cause of this condition is sarcoidosis. Its highly variable
      clinical presentation is challenging. Especially in patients suffering chronic
      kidney graft failure the nonspecific constitutional symptoms of sarcoidosis like
      fever, weight loss, arthralgia and fatigue may be easily misleading. CASE
      PRESENTATION: A 51 year old male developed hypercalcemia, arthralgia and B
      symptoms after explantation of his kidney graft because of suspected acute
      rejection. The removed kidney showed vasculopathy and tubulointerstitial
      nephritis, which had not been overt in the biopsy taken half a year earlier.
      Despite explantation and withdrawal of the immunosuppression the patient's
      general condition deteriorated progressively. A rapid rise in serum calcium
      finally provoked us to check for sarcoidosis. CT scans of the lungs, broncho
      alveolar-lavage and further lab tests confirmed the diagnosis. CONCLUSION: This
      case demonstrates that withdrawal of immunosuppressive drugs sometimes unmasks
      sarcoidosis. It should be considered as differential diagnosis even in
      hemodialysis patients, in whom other reasons for hypercalcemia are much more
      common.

PMID- 18053168
TI  - A meta-analysis on depression and subsequent cancer risk.
AB  - BACKGROUND: The authors tested the hypothesis that depression is a possible
      factor influencing the course of cancer by reviewing prospective epidemiological
      studies and calculating summary relative risks. METHODS: Studies were identified
      by computerized searches of Medline, Embase and PsycINFO. as well as manual
      searches of reference lists of selected publications. Inclusion criteria were
      cohort design, population-based sample, structured measurement of depression and
      outcome of cancer known for depressed and non-depressed subjects RESULTS:
      Thirteen eligible studies were identified. Based on eight studies with complete
      crude data on overall cancer, our summary relative risk (95% confidence interval)
      was 1.19 (1.06-1.32). After adjustment for confounders we pooled a summary
      relative risk of 1.12 (0.99-1.26).No significant association was found between
      depression and subsequent breast cancer risk, based on seven heterogeneous
      studies, with or without adjustment for possible confounders. Subgroup analysis
      of studies with a follow-up of ten years or more, however, resulted in a
      statistically significant summary relative risk of 2.50 (1.06-5.91).No
      significant associations were found for lung, colon or prostate cancer.
      CONCLUSION: This review suggests a tendency towards a small and marginally
      significant association between depression and subsequent overall cancer risk and
      towards a stronger increase of breast cancer risk emerging many years after a
      previous depression.

PMID- 18053169
TI  - Comparative evaluation of antiproliferative, antiangiogenic and apoptosis
      inducing potential of black tea polyphenols in the hamster buccal pouch
      carcinogenesis model.
AB  - BACKGROUND: To evaluate the relative chemopreventive efficacy of two black tea
      polyphenols, Polyphenon-B [P-B] and BTF-35 on 7,12-dimethylbenz [a]anthracene
      (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. METHODS: Hamsters were
      divided into 6 groups. The right buccal pouches of animals in groups 1-3 were
      painted with 0.5% of DMBA three times a week for 14 weeks. While hamsters in
      group 1 received no further treatment, animals in groups 2 and 3 received diet
      containing 0.05% P-B and BTF-35 respectively, four weeks before DMBA painting
      that was continued until the end of the experiments. Animals in groups 4 and 5
      were given P-B and BTF-35 alone respectively as in groups 2 and 3. Group 6
      animals served as the untreated control. All the animals were sacrificed after 18
      weeks. The expression of p21, cyclin D1, glutathione S-transferase pi (GST-P),
      nuclear factor kappa B (NF-kappaB), Bcl-2, Bax, cytochrome C, caspase-3, caspase
      9, poly(ADP-ribose) polymerase (PARP), cytokeratins and vascular endothelial
      growth factor (VEGF) was analysed by RT-PCR, immunohistochemical and Western blot
      analyses. RESULTS: DMBA treated animals developed buccal pouch carcinomas that
      displayed increased expression of p21, cyclin D1, GST-P, NF-kappaB, cytokeratins,
      VEGF and Bcl-2 with decreased expression of Bax, cytochrome C, caspase-3, caspase
      9, and PARP. Dietary administration of both P-B and BTF-35 reduced the incidence
      of DMBA-induced HBP carcinomas by modulating markers of cell proliferation, cell
      survival, tumour infiltration, angiogenesis, and apoptosis. CONCLUSION: The
      results of the present study provide a mechanistic basis for the chemopreventive
      potential of black tea polyphenols. The greater efficacy of BTF-35 in inhibiting
      HBP carcinogenesis and modulating multiple molecular targets may have a potential
      role in the prevention of oral cancer.

PMID- 18053170
TI  - Improvement of psychometric properties of a scale measuring inpatient
      satisfaction with care: a better response rate and a reduction of the ceiling
      effect.
AB  - BACKGROUND: The objective was to solve two problems of an already validated scale
      measuring inpatient opinion on care: 1) a high non-response rate for some items
      due to the "not applicable" response option and 2) a skewed score distribution
      with high ceiling effect. METHODS: The EQS-H scale ("echelle de qualite des soins
      en hospitalisation") comprised 26 items and 2 sub-scales of 13 items each,
      'quality of medical information' (MI) and 'relationships with staff and daily
      routine' (RS). Three studies were conducted: a first mono-centre study (n = 552,
      response rate = 83.4%, self-completion of the scale the day before discharge) to
      construct a shorter version of the scale without the items with high non-response
      rate and maintaining those useful to ensure good internal validity (construct,
      convergent and divergent) and reliability; a second mono-centre study (n = 1246,
      response rate = 77.9%, self-completion of the scale before discharge) to confirm
      psychometric properties of the new version; a third multi-centre national study
      (n = 886, response rate 41.7%, self-completion at home 15 days after discharge)
      to test a new response pattern in order to reduce ceiling effect. RESULTS: Six
      items having a non-response rate >20% were deleted, increasing rates of
      exhaustive response to all items from 15% to 48%. Factorial analysis supported
      the evidence for removing 4 more items to ensure good internal validity and
      reliability of the new version. These good results (initial variance explained:
      43%; Cronbach's alpha: 0.80 (MI) and 0.81 (RS)) were confirmed by the second
      study. The new response format produced a normalisation of the 2 scores with a
      large decrease in ceiling effect (25% to 4% for MI subscale and 61% to 8% for
      RS). Psychometric properties of the final version were excellent: the 2 subscales
      (8 items each) explained 66% of the variance in principal component analysis,
      Cronbach's alpha were respectively 0.92 (MI) and 0.93 (RS). CONCLUSION: The new
      version of the EQS-H has better psychometric properties than the previous one.
      Rates of missing values are lower, and score distribution is normalized. An
      English version of this scale focused on quality of medical information delivered
      and on relationship with staff already exists, and this could be useful to
      conduct cross-cultural studies of health care service quality.

PMID- 18053171
TI  - The 3' untranslated region of human Cyclin-Dependent Kinase 5 Regulatory subunit
      1 contains regulatory elements affecting transcript stability.
AB  - BACKGROUND: CDK5R1 plays a central role in neuronal migration and differentiation
      during central nervous system development. CDK5R1 has been implicated in
      neurodegenerative disorders and proposed as a candidate gene for mental
      retardation. The remarkable size of CDK5R1 3'-untranslated region (3'-UTR)
      suggests a role in post-transcriptional regulation of CDK5R1 expression. RESULTS:
      The bioinformatic study shows a high conservation degree in mammals and predicts
      several AU-Rich Elements (AREs). The insertion of CDK5R1 3'-UTR into luciferase
      3'-UTR causes a decreased luciferase activity in four transfected cell lines. We
      identified 3'-UTR subregions which tend to reduce the reporter gene expression,
      sometimes in a cell line-dependent manner. In most cases the quantitative
      analysis of luciferase mRNA suggests that CDK5R1 3'-UTR affects mRNA stability. A
      region, leading to a very strong mRNA destabilization, showed a significantly low
      half-life, indicating an accelerated mRNA degradation. The 3' end of the
      transcript, containing a class I ARE, specifically displays a stabilizing effect
      in neuroblastoma cell lines. We also observed the interaction of the stabilizing
      neuronal RNA-binding proteins ELAV with the CDK5R1 transcript in SH-SY5Y cells
      and identified three 3'-UTR sub-regions showing affinity for ELAV proteins.
      CONCLUSION: Our findings evince the presence of both destabilizing and
      stabilizing regulatory elements in CDK5R1 3'-UTR and support the hypothesis that
      CDK5R1 gene expression is post-transcriptionally controlled in neurons by ELAV
      mediated mechanisms. This is the first evidence of the involvement of 3'-UTR in
      the modulation of CDK5R1 expression. The fine tuning of CDK5R1 expression by 3'
      UTR may have a role in central nervous system development and functioning, with
      potential implications in neurodegenerative and cognitive disorders.

PMID- 18053172
TI  - Discrepancy in clinical versus radiological parameters describing deformity due
      to brace treatment for moderate idiopathic scoliosis.
AB  - BACKGROUND: The shape of the torso in patients with idiopathic scoliosis is
      considered to reflect the shape of the vertebral column, however the direct
      correlation between parameters describing clinical deformity and those
      characterizing radiological curvature was reported to be weak. It is not clear if
      the management proposed for scoliosis (physiotherapy, brace, surgery) affects
      equally the shape of the axial skeleton and the surface of the body. The aim of
      the study was to compare clinical deformity of (1) idiopathic scoliosis girls
      being under brace treatment for radiological curves of 25 to 40 degrees and (2)
      non treated scoliotic girls matched for age and Cobb angle. METHODS: Cross
      sectional study of 24 girls wearing the brace versus 26 girls without brace
      treatment, matched for age and Cobb angle. HYPOTHESIS: Patients wearing the brace
      for more than 6 months, when comparing to patients without brace, may present
      different external morphology of the trunk, in spite of having similar Cobb
      angle. Material. INCLUSION CRITERIA: girls, idiopathic scoliosis, growing age (10
      16 years), Cobb angle minimum 25 degrees , maximum 40 degrees . The braced group
      consisted of girls wearing a TLSO brace (Cheneau) for more than 6 months with
      minimum of 16 hours per day. The non-braced group consisted of girls first seen
      for their spinal deformity, previously not treated. The groups presented similar
      curve pattern. Methods. Scoliometer exam: angle of trunk rotation at three levels
      of the spine: upper thoracic, main thoracic, lumbar or thoracolumbar. The maximal
      angle was noted at each level and the sum of three levels was calculated.
      Posterior trunk symmetry index (POTSI) and Hump Sum were measured using surface
      topography. RESULTS: Cobb angle was 34.9 degrees +/- 4.8 degrees in braced and
      32.7 degrees +/- 4.9 degrees in un-braced patients (difference not significant).
      The age was 14.1 +/- 1.6 years in braced patients and 13.1 +/- 1.9 years in un
      braced group (p = 0.046). The value of angle of trunk rotation in the main
      curvature was 8.4 degrees +/- 2.7 degrees in braced and 11.4 degrees +/- 2.7
      degrees in un-braced patients (difference extremely significant, p = 0.0003). The
      value of the sum of angles of trunk rotation at three levels of the trunk was
      12.8 degrees +/- 4.6 degrees in braced and 16.5 degrees +/- 3.8 degrees in un
      braced patients (difference very significant, p = 0.0038). The POTSI did not
      differ significantly between the groups (p = 0.78), the Hump Sum values were not
      quite different (p = 0.07). CONCLUSION: (1) Adolescent girls wearing the brace
      for idiopathic scoliosis of 25 to 40 degrees of Cobb angle, reveal smaller
      clinical rotational deformity of their back than non-treated girls having similar
      radiological deformity. (2) Evaluation of the results of treatment for idiopathic
      scoliosis should consider parameters describing both clinical and radiological
      deformity.

PMID- 18053173
TI  - Does the spillage of petroleum products in Anopheles breeding sites have an
      impact on the pyrethroid resistance?
AB  - BACKGROUND: The emergence of Anopheles populations capable of withstanding lethal
      doses of insecticides has weakened the efficacy of most insecticide based
      strategies of vector control and, has highlighted the need for further studies on
      the mechanisms of insecticide resistance and the various factors selecting
      resistant populations of mosquitoes. This research targeted the analysis of
      breeding sites and the oviposition behaviour of susceptible and resistant
      populations of Anopheles in localities of spilled petroleum products. The aim was
      to establish the possible contribution of oil spillage in the selection of
      pyrethroid resistance in malaria vectors. METHODS: Anopheles breeding sites were
      identified and the insecticide susceptibility of the Anopheles gambiae
      populations mapped in 15 localities of South Western Nigeria. The presence of oil
      particles as well as the turbidity, the dissolved oxygen and the pH of each
      identified breeding site was recorded. Data were cross-analysed to correlate the
      habitat types and the insecticide susceptibility status of emerging mosquitoes.
      The second phase of this study was basically a laboratory model to provide more
      information on the implication of the spillage of petroleum on the selection of
      pyrethroid resistance in An. gambiae. RESULTS: Moderate levels of resistance
      following exposure to permethrin-impregnated papers were recorded with the
      majority of An. gambiae samples collected in the South Western Nigeria. Data from
      this study established a link between the constituency of the breeding sites and
      the resistance status of the emerging Anopheles. CONCLUSION: This study has
      revealed the segregational occupation of breeding habitats by pyrethroid
      resistant and susceptible strains of An. gambiae in south-western Nigeria.
      Compiled results from field and laboratory research point out clear relationships
      between oil spillage and pyrethroid resistance in malaria vectors. The
      identification of this factor of resistance could serve as strong information in
      the management of insecticide resistance in some West African settings.

PMID- 18053174
TI  - Identification of a novel truncating PALB2 mutation and analysis of its
      contribution to early-onset breast cancer in French-Canadian women.
AB  - BACKGROUND: PALB2 has recently been identified as a breast cancer susceptibility
      gene. PALB2 mutations are rare causes of hereditary breast cancer but may be
      important in countries such as Finland where a founder mutation is present. We
      sought to estimate the contribution of PALB2 mutations to the burden of breast
      cancer in French Canadians from Quebec. METHODS: We screened all coding exons of
      PALB2 in a sample of 50 French-Canadian women diagnosed with either early-onset
      breast cancer or familial breast cancer at a single Montreal hospital. The
      genetic variants identified in this sample were then studied in 356 additional
      women with breast cancer diagnosed before age 50 and in 6,448 newborn controls.
      RESULTS: We identified a single protein-truncating mutation in PALB2 (c.2323 C>T,
      resulting in Q775X) in 1 of the 50 high-risk women. This variant was present in 2
      of 356 breast cancer cases and in none of 6,440 newborn French-Canadian controls
      (P = 0.003). We also identified two novel new non-synonymous single nucleotide
      polymorphisms in exon 4 of PALB2 (c.5038 A>G [I76V] and c.5156 G>T [G115V]).
      G115V was found in 1 of 356 cases and in 15 of 6,442 controls (P = 0.6). The I76V
      variant was not identified in either the extended case series or the controls.
      CONCLUSION: We have identified a novel truncating mutation in PALB2. The mutation
      was found in approximately 0.5% of unselected French-Canadian women with early
      onset breast cancer and appears to have a single origin. Although mutations are
      infrequent, PALB2 can be added to the list of breast cancer susceptibility genes
      for which founder mutations have been identified in the French-Canadian
      population.

PMID- 18053175
TI  - Therapy-refractory Panton Valentine Leukocidin-positive community-acquired
      methicillin-sensitive Staphylococcus aureus sepsis with progressive metastatic
      soft tissue infection: a case report.
AB  - We report a case of fulminant multiple organ failure including the Acute
      Respiratory Distress Syndrome (ARDS), haemodynamic, and renal failure due to
      community-acquired methicillin-sensitive Panton Valentine Leukocidin (PVL)
      positive spa-type 284 (ST121) Staphylococcus aureus septic shock. The patient's
      first clinical symptom was necrotizing pneumonia. Despite organism-sensitive
      triple antibiotic therapy with linezolid, imipenem and clindamycin from the first
      day of treatment, progressive abscess formation in multiple skeletal muscles was
      observed. As a result, repeated surgical interventions became necessary. Due to
      progressive soft tissue infection, the anti-microbial therapy was changed to a
      combination of clindamycin and daptomycin. Continued surgical and antimicrobial
      therapy finally led to a stabilisation of the patients' condition. The clinical
      course of our patient underlines the existence of a "PVL-syndrome" which is
      independent of in vitro Staphylococcus aureus susceptibility. The PVL-syndrome
      should not only be considered in patients with soft tissue or bone infection, but
      also in patients with pneumonia. Such a condition, which may easily be mistaken
      for uncomplicated pneumonia, should be treated early, aggressively and over a
      long period of time in order to avoid relapsing infection.

PMID- 18053176
TI  - Adeno-associated virus (AAV)-mediated suppression of Ca2+/calmodulin kinase IV
      activity in the nucleus accumbens modulates emotional behaviour in mice.
AB  - BACKGROUND: Calcium/calmodulin-dependent protein kinase IV (CaMKIV) controls
      activity-dependent gene transcription by regulating the activity of the cyclic
      AMP response element binding protein (CREB). This signaling pathway is involved
      in gating emotional responses in the CNS but previous studies did not address the
      potential roles of CaMKIV in discrete brain regions. In the present study, we
      aimed at specifically dissecting the role of CaMKIV in the nucleus accumbens of
      adult mice. RESULTS: We used recombinant adeno-associated virus (rAAV)-mediated
      gene transfer of a dominant-negative CaMKIV variant (rAAV-dnCaMKIV) to inhibit
      endogenous CaMKIV in the nucleus accumbens. rAAV-dnCaMKIV treated animals were
      subjected to a battery of tests including, prepulse inhibition of the acoustic
      startle response, open field, social interaction and anxiety-related behaviour.
      We found that basal locomotor activity in the open field, and prepulse inhibition
      or startle performance were unaltered in mice infected with rAAV-dnCaMKIV in the
      nucleus accumbens. However, anxiogenic effects were revealed in social
      interaction testing and the light/dark emergence test. CONCLUSION: Our findings
      suggest a modulatory role of CaMKIV in the nucleus accumbens in anxiety-like
      behaviour but not sensorimotor gating.

PMID- 18053177
TI  - Recurrence of suicidal ideation due to treatment with antidepressants in anxiety
      disorder: a case report.
AB  - This report describes a patient suffering from panic disorder who developed
      repeated suicidal ideation specifically due to the treatment with Venlafaxine. A
      first suicide attempt years ago occurred while being treated with Venlafaxine.
      Subsequent treatment with SSRIs or other antidepressants involved no suicidal
      ideation. Re-commencement of Venlafaxine four years later immediately led to a
      second suicide attempt. This unwanted effect subsided immediately after switching
      to another SNRI (i.e. Duloxetine). The case report underlines the importance of
      onset of suicide risk in panic disorders due to specific antidepressants.

PMID- 18053178
TI  - Health-related quality of life of child and adolescent retinoblastoma survivors
      in the Netherlands.
AB  - BACKGROUND: To assess health-related quality of life (HRQoL) in children (8-11
      years) and adolescents (12-18 years) who survived retinoblastoma (RB), by means
      of the KIDSCREEN self-report questionnaire and the proxy-report version. METHODS:
      This population-based cross-sectional study (participation rate 70%) involved 65
      RB survivors (8-18 years) and their parents. Child/adolescents' and parents'
      perception of their youth's HRQoL was assessed using the KIDSCREEN, and the
      results were compared with Dutch reference data. Relations with gender, age,
      marital status of the parents, and visual acuity were analyzed. RESULTS: RB
      survivors reported better HRQoL than did the Dutch reference group on the
      dimensions "moods and emotions" and "autonomy". Increased ratings of HRQoL in RB
      survivors were mainly seen in perceptions of the younger children and adolescent
      girls. RB survivors with normal visual acuity scored higher on "physical well
      being" than visually impaired survivors. Age was negatively associated with the
      dimensions "psychological well-being", "self-perception" (according to the child
      and parent reports) and "parent relations and home life" (according to the
      child). "Self-perception" was also negatively associated with visual acuity
      (according to the child). Only parents of young boys surviving RB reported lower
      on "autonomy" than the reference group, and parents of low visual acuity and
      blind RB survivors reported higher on "autonomy" than parents of visually
      unimpaired survivors. Survivors' perceptions and parents' perceptions correlated
      poorly on all HRQoL dimensions. CONCLUSION: RB survivors reported a very good
      HRQoL compared with the Dutch reference group. The perceptions related to HRQoL
      differ substantially between parents and their children, i.e. parents judge the
      HRQoL of their child to be relatively poorer. Although the results are
      reassuring, additional factors of HRQoL that may have more specific relevance,
      such as psychological factors or coping skills, should be explored.

PMID- 18053179
TI  - Bioinformatics process management: information flow via a computational journal.
AB  - This paper presents the Bioinformatics Computational Journal (BCJ), a framework
      for conducting and managing computational experiments in bioinformatics and
      computational biology. These experiments often involve series of computations,
      data searches, filters, and annotations which can benefit from a structured
      environment. Systems to manage computational experiments exist, ranging from
      libraries with standard data models to elaborate schemes to chain together input
      and output between applications. Yet, although such frameworks are available,
      their use is not widespread-ad hoc scripts are often required to bind
      applications together. The BCJ explores another solution to this problem through
      a computer based environment suitable for on-site use, which builds on the
      traditional laboratory notebook paradigm. It provides an intuitive, extensible
      paradigm designed for expressive composition of applications. Extensive features
      facilitate sharing data, computational methods, and entire experiments. By
      focusing on the bioinformatics and computational biology domain, the scope of the
      computational framework was narrowed, permitting us to implement a capable set of
      features for this domain. This report discusses the features determined critical
      by our system and other projects, along with design issues. We illustrate the use
      of our implementation of the BCJ on two domain-specific examples.

PMID- 18053180
TI  - How can developing countries harness biotechnology to improve health?
AB  - BACKGROUND: The benefits of genomics and biotechnology are concentrated primarily
      in the industrialized world, while their potential to combat neglected diseases
      in the developing world has been largely untapped. Without building developing
      world biotechnology capacity to address local health needs, this disparity will
      only intensify. To assess the potential of genomics to address health needs in
      the developing world, the McLaughlin-Rotman Centre for Global Health, along with
      local partners, organized five courses on Genomics and Public Health Policy in
      the developing world. The overall objective of the courses was to collectively
      explore how to best harness genomics to improve health in each region. This
      article presents and analyzes the recommendations from all five courses.
      DISCUSSION: In this paper we analyze recommendations from 232 developing world
      experts from 58 countries who sought to answer how best to harness biotechnology
      to improve health in their regions. We divide their recommendations into four
      categories: science; finance; ethics, society and culture; and politics. SUMMARY:
      The Courses' recommendations can be summarized across the four categories listed
      above: SCIENCE: - Collaborate through national, regional, and international
      networks- Survey and build capacity based on proven models through education,
      training, and needs assessments FINANCE: - Develop regulatory and intellectual
      property frameworks for commercialization of biotechnology- Enhance funding and
      affordability of biotechnology- Improve the academic-industry interface and the
      role of small and medium enterprise ETHICS, SOCIETY, CULTURE: - Develop public
      engagement strategies to inform and educate the public about developments in
      genomics and biotechnology- Develop capacity to address ethical, social and
      cultural issues- Improve accessibility and equity POLITICS: - Strengthen
      understanding, leadership and support at the political level for biotechnology-
      Develop policies outlining national biotechnology strategyThese recommendations
      provide guidance for all those interested in supporting science, technology, and
      innovation to improve health in the developing world. Applying these
      recommendations broadly across sectors and regions will empower developing
      countries themselves to harness the benefits of biotechnology and genomics for
      billions who have long been excluded.

PMID- 18053181
TI  - Malignant perivascular epithelioid cell tumor (PEComa) of the uterus with late
      renal and pulmonary metastases: a case report with review of the literature.
AB  - BACKGROUND: Perivascular epithelioid cell tumor (PEComa), other than
      angiomyolipoma (AML), clear cell sugar tumor (CCST), and lymphangioleiomyomatosis
      (LAM), is a very rare mesenchymal tumor with an unpredictable natural history.
      The uterus is the most prevalent reported site of involvement of PEComa-not
      otherwise specified (PEComa-NOS). To the best of our knowledge, about 100 PEComa
      NOS have been reported in the English Language medical literature, of which 38
      were uterine PEComa-NOS. These reported cases of uterine PEComa-NOS have usually
      shown clinically benign behavior, but 13 tumors, three of them associated with
      tuberous sclerosis complex (TSC), exhibited local aggressive behavior and four of
      them showed distant metastases. CASE PRESENTATION: We report the case of a 59
      year-old woman, who presented with renal and pulmonary lesions seven years after
      the initial diagnosis of uterine leiomyosarcoma. Left nephrectomy and right
      middle lobe wedge resection were performed. Histological and immunohistochemical
      analysis of the renal and pulmonary lesions, in addition to retrospective re
      evaluation of the previous uterine tumor, led to the final diagnosis of malignant
      uterine PEComa with late renal and pulmonary metastases. All three lesions had
      the typical histological appearance of PEComa-NOS showing a biphasic growth
      pattern with continuous transition between spindle cells and epithelioid cells,
      often arranged around vascular spaces. Immunohistochemically, the tumor cells of
      both phenotypes in all three lesions stained for melanocytic (HMB-45 and Melan
      A/MART-1) and myoid (desmin, smooth muscle actin, and muscle-specific actin/all
      muscle actin/HHF-35) markers. CONCLUSION: The findings indicate that despite the
      small number of reported cases, PEComas-NOS should be considered tumors of
      uncertain malignant potential, and metastases to other organs might become
      evident even several years after the primary diagnosis.

PMID- 18053182
TI  - Seizures as the first manifestation of chromosome 22q11.2 deletion syndrome in a
      40-year old man: a case report.
AB  - BACKGROUND: The microdeletion of chromosome 22q11.2 is the most common human
      deletion syndrome. It typically presents early in life and is rarely considered
      in adult patients. As part of the manifestations of this condition, patients can
      have parathyroid glandular involvement ranging from hypocalcemic
      hypoparathyroidism to normocalcemia with normal parathryroid hormone levels. The
      first manifestation of the syndrome might be seizures due to profound
      hypocalcemia. CASE PRESENTATION: A 40-year-old man without significant past
      medical history presented with a new-onset generalized tonic-clonic seizure. He
      had no personal history of hypocalcemia or seizures. Physical examination was
      remarkable for short stature, hypertelorism, prominent forehead and nasal voice.
      His initial laboratory examination showed hypocalcemia (Calcium 5.2 mg/dl and
      Calcium ionized 0.69 mmol/l) with hypoparathyroidism (Parathyroid hormone intact
      < 2.5 pg/ml. NV: 14-72 pg/ml). Urine Calcium was 3 mg/dl on a spot and 88 mg in a
      24-hour urine collection (NV: 100-300 mg/24 hs). The electrocardiogram showed a
      prolonged corrected QT interval. Echocardiogram, abdominal ultrasound and
      electroencephalogram were normal. A computer tomography of the brain showed basal
      ganglia calcification. The subtle physical findings and the presence of
      idiopathic hypoparathyroidism motivated the performance of fluorescent in situ
      hybridization which demonstrated a microdeletion on one of the homologs 22q11.2.
      The patient was treated with calcium citrate and calcitriol with good response.
      CONCLUSION: Microdeletion of chromosome 22q11.2 is among the most clinically
      variable syndromes, with more than 180 features associated with the deletion. It
      has a variable phenotypical expression, requiring a high level of awareness for
      its early diagnosis. Seizures, related to marked hypocalcemia due to idiopathic
      hypoparathyroidism, might be the presenting feature in an adult patient with this
      syndrome.

PMID- 18053183
TI  - Glycine propionyl-L-carnitine increases plasma nitrate/nitrite in resistance
      trained men.
AB  - : We have recently demonstrated that oral intake of glycine propionyl-L-carnitine
      (GPLC) increases plasma nitrate/nitrite (NOx), a surrogate measure of nitric
      oxide production. However, these findings were observed at rest, and in
      previously sedentary subjects. PURPOSE: In the present study, we sought to
      determine the impact of oral GPLC on plasma NOx at rest and in response to a
      period of reactive hyperemia in resistance trained men. METHODS: Using a double
      blind, crossover design, 15 healthy men (24 +/- 4 years) were assigned to GPLC (3
      g/d PLC + 1044 mg glycine) and a placebo in random order, for a four-week period,
      with a two-week washout between condition assignment. Blood samples were taken
      from subjects at rest and at 0, 3, and 10 minutes following an ischemia
      reperfusion protocol (six minutes of upper arm cuff occlusion at 200 mmHg
      followed by rapid reperfusion with cuff removal). Blood samples were taken from a
      forearm vein from the same arm used for the protocol and analyzed for total
      nitrate/nitrite. Data are presented as mean +/- SEM. RESULTS: A condition main
      effect (p = 0.0008) was noted for NOx, with higher values in subjects when using
      GPLC (45.6 +/- 2.8 mumol.L-1) compared to placebo (34.9 +/- 1.2 mumol.L-1). No
      time main effect was noted (p = 0.7099), although values increased approximately
      12% from rest (37.7 +/- 2.7 mumol.L-1) to a peak at 10 minutes post protocol
      (42.3 +/- 3.3 mumol.L-1). The interaction effect was not significant (p =
      0.8809), although paired time contrasts revealed higher values for GPLC compared
      to placebo at 3 (48.2 +/- 6.7 vs. 34.9 +/- 2.4 mumol.L-1; p = 0.033) and 10 (48.8
      +/- 5.9 vs. 35.7 +/- 2.1 mumol.L-1; p = 0.036) minutes post protocol, with non
      statistically significant differences noted at rest (41.8 +/- 4.5 vs. 33.6 +/-
      2.5 mumol.L-1; p = 0.189) and at 0 minutes (43.6 +/- 5.1 vs. 35.4 +/- 2.7 mumol.L
      1; p = 0.187) post protocol. An analysis by subject (collapsed across time)
      indicated that 11 of the 15 subjects experienced an increase in NOx with GPLC
      treatment. CONCLUSION: These findings indicate that short-term oral GPLC
      supplementation can increase NOx in resistance trained men. However, as with many
      dietary supplements, there exist both "responders" and "non-responders" to
      treatment. Future work may focus on the mechanisms for the discrepancy in
      response to GPLC supplementation for purposes of NOx elevation.

PMID- 18053184
TI  - Real-time intelligent pattern recognition algorithm for surface EMG signals.
AB  - BACKGROUND: Electromyography (EMG) is the study of muscle function through the
      inquiry of electrical signals that the muscles emanate. EMG signals collected
      from the surface of the skin (Surface Electromyogram: sEMG) can be used in
      different applications such as recognizing musculoskeletal neural based patterns
      intercepted for hand prosthesis movements. Current systems designed for
      controlling the prosthetic hands either have limited functions or can only be
      used to perform simple movements or use excessive amount of electrodes in order
      to achieve acceptable results. In an attempt to overcome these problems we have
      proposed an intelligent system to recognize hand movements and have provided a
      user assessment routine to evaluate the correctness of executed movements.
      METHODS: We propose to use an intelligent approach based on adaptive neuro-fuzzy
      inference system (ANFIS) integrated with a real-time learning scheme to identify
      hand motion commands. For this purpose and to consider the effect of user
      evaluation on recognizing hand movements, vision feedback is applied to increase
      the capability of our system. By using this scheme the user may assess the
      correctness of the performed hand movement. In this work a hybrid method for
      training fuzzy system, consisting of back-propagation (BP) and least mean square
      (LMS) is utilized. Also in order to optimize the number of fuzzy rules, a
      subtractive clustering algorithm has been developed. To design an effective
      system, we consider a conventional scheme of EMG pattern recognition system. To
      design this system we propose to use two different sets of EMG features, namely
      time domain (TD) and time-frequency representation (TFR). Also in order to
      decrease the undesirable effects of the dimension of these feature sets,
      principle component analysis (PCA) is utilized. RESULTS: In this study, the
      myoelectric signals considered for classification consists of six unique hand
      movements. Features chosen for EMG signal are time and time-frequency domain. In
      this work we demonstrate the capability of an EMG pattern recognition system
      using ANFIS as classifier with a real-time learning method. Our results reveal
      that the utilized real-time ANFIS approach along with the user evaluation
      provides a 96.7% average accuracy. This rate is superior to the previously
      reported result utilizing artificial neural networks (ANN) real-time method 1.
      CONCLUSION: This study shows that ANFIS real-time learning method coupled with
      mixed time and time-frequency features as EMG features can provide acceptable
      results for designing sEMG pattern recognition system suitable for hand
      prosthesis control.

PMID- 18053185
TI  - Increased serum levels of TGFbeta1 in children with localized scleroderma.
AB  - BACKGROUND: There are neither sensitive nor specific laboratory tests for
      measuring disease activity in localized scleroderma (LS). Monitoring is done
      almost exclusively by clinical assessment. Our aim was to determine whether serum
      concentrations of TGFbeta1 are a good biomarker of disease activity in children
      with LS. METHODS: 55 pediatric patients with LS were divided into sub-types
      according to their main lesion; morphea, generalized morphea, linear scleoderma
      affecting a limb or the face. The lesions were further categorized by overall
      clinical assessment into active, inactive, and indeterminate groups according to
      disease activity. Serum TGFbeta1 concentration levels were measured by enzyme
      linked immunosorbent assay (ELISA), analyzed and correlated with disease subtypes
      and disease activity. RESULTS: The mean TGFbeta1 concentration were significantly
      higher in the patient group (51393 +/- 33953 pg/ml) than in the control group
      (9825 +/- 5287 pg/ml) (P < 0.001). The mean concentration were elevated in all
      the disease subtypes, and did not correlate with disease duration or activity.
      CONCLUSION: Serum concentration of TGFbeta1 were elevated in patients with all
      subtypes of LS irrespective of clinical disease activity. Although TGFbeta1 may
      play an important role in the pathogenesis of local skin fibrosis, circulating
      blood levels of molecules known to act locally may not be useful biomarkers of
      disease activity.

PMID- 18053186
TI  - Modifiable risk factors remain significant causes of medium term mortality after
      first time Coronary artery bypass grafting.
AB  - BACKGROUND: Whilst there is much current data on early outcomes after Coronary
      artery bypass grafting(CABG), there is relatively little data on medium term
      outcomes in the current era. The purpose of this study is to present a single
      surgeon series comprising of all first time CABG patients operated on with the
      technique of cross clamp fibrillation from Feb-1996 to through to Jan-2003, and
      to seek risk factors for medium term mortality in these patients. METHODS: Data
      was collected from Hospital Episode Statistics and departmental patient
      administration and tracking systems and cross checked using database techniques.
      Patient outcomes were searched using the National Health Service strategic
      tracing service. RESULTS: Mean follow up was 5.3 years(0-9.4 years) and was
      complete for all patients. 30-day survival was 98.4%, 1-year survival 95% and 8
      year survival 79%. Cox-regression analysis revealed that several modifiable pre
      operative risk factors remain significant predictors of medium term mortality,
      including Diabetes(Hazard Ratio(HR) 1.73, 95%CI 1.21-2.45), Chromic obstructive
      pulmonary disease(HR 2.02, 95%CI 1.09-3.72), Peripheral vascular disease(HR 1.68,
      95%CI 1.13-2.5), Body mass index>30(HR 1.54, 95%CI 1.08-2.20) and current smoker
      at operation(HR 1.67, 95%CI 1.03-2.72). However hypertension(HR 1.31, 95%CI 0.95
      1.82) and Hypercholestrolaemia(HR 0.81, 95%CI 0.58-1.13) were not predictive
      which may reflect adequate post-operative control. CONCLUSION: Coronary artery
      bypass surgery using cross clamp fibrillation is associated with a very low
      operative mortality. Medium term survival is also good but risk factors such as
      smoking at operation, Chronic obstructive pulmonary disease, obesity and diabetes
      negatively impact this survival and should be aggressively treated in the years
      post-surgery.

PMID- 18053187
TI  - Cerebellum morphogenesis: the foliation pattern is orchestrated by multi-cellular
      anchoring centers.
AB  - BACKGROUND: The cerebellum has a striking morphology consisting of folia
      separated by fissures of different lengths. Since folia in mammals likely serve
      as a broad platform on which the anterior-posterior organization of the sensory
      motor circuits of the cerebellum are built, it is important to understand how
      such complex morphology arises. RESULTS: Using a combination of genetic inducible
      fate mapping, high-resolution cellular analysis and mutant studies in mouse, we
      demonstrate that a key event in initiation of foliation is the acquisition of a
      distinct cytoarchitecture in the regions that will become the base of each
      fissure. We term these regions 'anchoring centers'. We show that the first
      manifestation of anchoring centers when the cerebellar outer surface is smooth is
      an increase in proliferation and inward thickening of the granule cell
      precursors, which likely causes an associated slight invagination of the Purkinje
      cell layer. Thereafter, granule cell precursors within anchoring centers become
      distinctly elongated along the axis of the forming fissure. As the outer
      cerebellar surface begins to fold inwards, Bergmann glial fibers radiate in
      towards the base of the immature fissure in a fan shape. Once the anchoring
      center is formed, outgrowth of folia seems to proceed in a self-sustaining manner
      driven by granule cell migration along Bergmann glial fibers. Finally, by
      analyzing a cerebellum foliation mutant (Engrailed 2), we demonstrate that
      changing the timing of anchoring center formation leads to predictable changes in
      the shape and size of the surrounding folia. CONCLUSION: We present a new
      cellular model of the initial formation of cerebellar fissures with granule cells
      providing the driving physical force. Both the precise timing of the appearance
      of anchoring centers at the prospective base of each fissure and the subsequent
      coordinated action of granule cells and Bergmann glial fibers within the
      anchoring centers dictates the shape of the folia.

PMID- 18053188
TI  - International Physical Activity Questionnaire (IPAQ) and New Zealand Physical
      Activity Questionnaire (NZPAQ): a doubly labelled water validation.
AB  - BACKGROUND: Accurate measurement of physical activity is a pre-requisite for
      monitoring population health and for evaluating effective interventions. The
      International Physical Activity Questionnaire (IPAQ) is used as a comparable and
      standardised self-report measure of habitual physical activity of populations
      from different countries and socio-cultural contexts. The IPAQ has been modified
      to produce a New Zealand physical activity questionnaire (NZPAQ). The aim of this
      study was to validate the IPAQ and NZPAQ against doubly labelled water (DLW).
      METHOD: Total energy expenditure (TEE) was measured over a 15-day period using
      DLW. Activity-related energy expenditure (AEE) was estimated by subtracting the
      energy expenditure from resting metabolic rate and thermic effect of feeding from
      TEE. The IPAQ (long form) and NZPAQ (short form) were completed at the end of
      each 7-day period. Activity-related energy expenditure (IPAQAEE and NZPAQAEE) was
      calculated from each questionnaire and compared to DLWAEE. RESULTS: Thirty six
      adults aged 18 to 56 years (56% female) completed all measurements. Compared to
      DLWAEE, IPAQAEE and NZPAQAEE on average underestimated energy expenditure by 27%
      and 59%, respectively. There was good agreement between DLWAEE and both IPAQAEE
      and NZPAQAEE at lower levels of physical activity. However there was marked
      underestimation of questionnaire-derived energy expenditure at higher levels of
      activity. CONCLUSION: Both the IPAQ and NZPAQ instruments have a demonstrated
      systematic bias toward underestimation of physical activity-related energy
      expenditure at higher levels of physical activity compared to DLW. Appropriate
      calibration factors could be used to correct for measurement error in physical
      activity questionnaires and hence improve estimation of AEE.

PMID- 18053189
TI  - Geographical information system and access to HIV testing, treatment and
      prevention of mother-to-child transmission in conflict affected Northern Uganda.
AB  - OBJECTIVES: Using Geographical Information System (GIS) as a tool to determine
      access to and gaps in providing HIV counselling and testing (VCT), treatment
      (ART) and mother-to-child transmission (PMTCT) services in conflict affected
      northern Uganda. METHODS: Cross-sectional data on availability and utilization,
      and geo-coordinates of health facilities providing VCT, PMTCT, and ART were
      collected in order to determine access. ArcView software produced maps showing
      locations of facilities and Internally Displaced Population(IDP) camps. FINDINGS:
      There were 167 health facilities located inside and outside 132 IDP camps with
      VCT, PMTCT and ART services provided in 32 (19.2%), 15 (9%) and 10 (6%)
      facilities respectively. There was uneven availability and utilization of
      services and resources among districts, camps and health facilities. Inadequate
      staff and stock-out of essential commodities were found in lower health facility
      levels. Provision of VCT was 100% of the HSSP II target at health centres IV and
      hospitals but 28% at HC III. For PMTCT and ART, only 42.9% and 20% of the
      respective targets were reached at the health centres IV. CONCLUSION: Access to
      VCT, PMTCT and ART services was geographically limited due to inadequacy and
      heterogeneous dispersion of these services among districts and camps. GIS mapping
      can be effective in identifying service delivery gaps and presenting complex data
      into simplistic results hence can be recommended in need assessments in conflict
      settings.

PMID- 18053190
TI  - Possible implications of an accessory abductor digiti minimi muscle: a case
      report.
AB  - BACKGROUND: Accessory ADM was first reported in 1868 although muscular, vascular
      and nervous variations of the hypothenar eminence are rare, contrary to anomalous
      muscles in the wrist which are relatively common. CASE PRESENTATION: This case
      report presents a bilateral variation of an accessory abductor digiti minimi
      muscle in a male specimen. Ulnar artery and ulnar nerves were taken into account
      regarding their position and trajectory related to this variation. CONCLUSION:
      Muscle size may be an important factor in considering whether a variation is able
      to produce neurovascular compression and clinical implications.

PMID- 18053191
TI  - Bortezomib in combination with celecoxib in patients with advanced solid tumors:
      a phase I trial.
AB  - BACKGROUND: COX-2 inhibitors, such as celecoxib, and ubiquitin-proteasome pathway
      inhibitors, such as bortezomib, can down-regulate NF-kappaB, a transcription
      factor implicated in tumor growth. The objective of this study was to determine
      the maximum tolerated dose and dose-limiting toxicities of bortezomib in
      combination with celecoxib in patients with advanced solid tumors. METHODS:
      Patients received escalating doses of bortezomib either on a weekly schedule
      (days 1, 8, 15, 22, and 29 repeated every 42 days) or on a twice-weekly
      administration schedule (days 1, 4, 8, and 11 repeated every 21 days), in
      combination with escalating doses of celecoxib twice daily throughout the study
      period from 200 mg to 400 mg twice daily. RESULTS: No dose-limiting toxicity was
      observed during the study period. Two patients had stable disease lasting for
      four and five months each, and sixteen patients developed progressive disease.
      CONCLUSION: The combination of bortezomib and celecoxib was well tolerated,
      without dose limiting toxicities observed throughout the dosing ranges tested,
      and will be studied further at the highest dose levels investigated. TRIAL
      REGISTRATION NUMBER: NCT00290680.

PMID- 18053192
TI  - Management of acquired bronchobiliary fistula: 3 case reports and a literature
      review.
AB  - Bronchobiliary fistula (BBF), which often presents with bilioptysis, is an
      abnormal communication between the bronchial system and biliary tree. It is a
      complication associated with a high mortality rate and requires a well-planned
      management strategy. Although hydatid disease is still the leading cause,
      extensive surgical interventions and invasive procedures of the liver have
      altered the profile of patients in recent decades. This paper presents 3 cases of
      BBF and reviews the literature regarding the treatment options generally mandated
      by clinical presentation and the underlying disease.

PMID- 18053193
TI  - Fibroma with minor sex cord elements--an incidental finding in a normal sized
      ovary. A case report with literature review.
AB  - Ovarian fibroma with minor sex cord element is a rare neoplasm. Microscopically
      it is composed of predominantly fibromatous or a thecomatous tumor containing
      scattered minor sex cord elements in less than 10% of the tumor area.A case of
      fibroma with minor sex cord elements discovered incidentally in a normal sized
      ovary in a patient who presented with dysfunctional uterine bleeding is being
      presented. This is the first case report describing this entity in a normal sized
      ovary as an incidental finding.

PMID- 18053194
TI  - The effect of phosphatidylserine on golf performance.
AB  - BACKGROUND: A randomized, double-blind, placebo-controlled study was performed to
      evaluate the effect of oral phosphatidylserine (PS) supplementation on golf
      performance in healthy young golfers with handicaps of 15-40. METHODS: Perceived
      stress, heart rate and the quality of the ball flight was evaluated before (pre
      test) and after (post-test) 42 days of 200 mg per day PS (n = 10) or placebo (n =
      10) intake in the form of a nutritional bar. Subjects teed-off 20 times aiming at
      a green 135 meters from the tee area. RESULTS: PS supplementation significantly
      increased (p < 0.05) the number of good ball flights (mean: pre-test 8.3 +/- 3.5,
      post-test 10.1 +/- 3.0), whereas placebo intake (mean: pre-test 7.8 +/- 2.4, post
      test 7.9 +/- 3.6) had no effect. PS supplementation showed a trend towards
      improving perceived stress levels during teeing-off (mean: pre-test 5.8 +/- 2.0,
      post-test 4.0 +/- 2.0, p = 0.07), whereas stress levels remained unchanged in the
      placebo group (mean: pre-test: 5.1 +/- 2.0, post-test: 5.1 +/- 3.1).
      Supplementation did not influence mean heart rate in either group. CONCLUSION: It
      is concluded that six weeks of PS supplementation shows a statistically not
      significant tendency (p = 0.07) to improve perceived stress levels in golfers and
      significantly improves (p < 0.05) the number of good ball flights during tee-off
      which might result in improved golf scores.

PMID- 18053195
TI  - Specific components of face perception in the human fusiform gyrus studied by
      tomographic estimates of magnetoencephalographic signals: a tool for the
      evaluation of non-verbal communication in psychosomatic paradigms.
AB  - AIMS: The aim of this study was to determine the specific spatiotemporal
      activation patterns of face perception in the fusiform gyrus (FG). The FG is a
      key area in the specialized brain system that makes possible the recognition of
      face with ease and speed in our daily life. Characterization of FG response
      provides a quantitative method for evaluating the fundamental functions that
      contribute to non-verbal communication in various psychosomatic paradigms.
      METHODS: The MEG signal was recorded during passive visual stimulus presentation
      with three stimulus types - Faces, Hands and Shoes. The stimuli were presented
      separately to the central and peripheral visual fields. We performed statistical
      parametric mapping (SPM) analysis of tomographic estimates of activity to compare
      activity between a pre- and post-stimulus period in the same object (baseline
      test), and activity between objects (active test). The time course of regional
      activation curves was analyzed for each stimulus condition. RESULTS: The SPM
      baseline test revealed a response to each stimulus type, which was very compact
      at the initial segment of main M(FG)170. For hands and shoes the area of
      significant change remains compact. For faces the area expanded widely within a
      few milliseconds and its boundaries engulfed the other object areas. The active
      test demonstrated that activity for faces was significantly larger than the
      activity for hands. The same face specific compact area as in the baseline test
      was identified, and then again expanded widely. For each stimulus type and
      presentation in each one of the visual fields locations, the analysis of the time
      course of FG activity identified three components in the FG: M(FG)100, M(FG)170,
      and M(FG)200 - all showed preference for faces. CONCLUSION: Early compact face
      specific activity in the FG expands widely along the occipito-ventral brain
      within a few milliseconds. The significant difference between faces and the other
      object stimuli in M(FG)100 shows that processing of faces is already
      differentiated from processing of other objects within 100 ms. Standardization of
      the three face-specific MEG components could have diagnostic value for the
      integrity of the initial process of non-verbal communication in various
      psychosomatic paradigms.

PMID- 18053196
TI  - Case-cohort design in practice - experiences from the MORGAM Project.
AB  - When carefully planned and analysed, the case-cohort design is a powerful choice
      for follow-up studies with multiple event types of interest. While the literature
      is rich with analysis methods for case-cohort data, little is written about the
      designing of a case-cohort study. Our experiences in designing, coordinating and
      analysing the MORGAM case-cohort study are potentially useful for other studies
      with similar characteristics. The motivation for using the case-cohort design in
      the MORGAM genetic study is discussed and issues relevant to its planning and
      analysis are studied. We propose solutions for appending the earlier case-cohort
      selection after an extension of the follow-up period and for achieving maximum
      overlap between earlier designs and the case-cohort design. Approaches for
      statistical analysis are studied in a simulation example based on the MORGAM
      data.

PMID- 18053197
TI  - Tumors: too sweet to remember?
AB  - Immunity, based on a natural and an educated system, is responsible for
      recognition and elimination of infectious particles, cellular waste, modified
      self and transformed cells. This dual system guarantees that dangerous particles
      are removed immediately after appearance and that a memory with maturated weapons
      exists, if the organism is re-infected by the same particle. For malignant cells,
      however, the immune response seems to be restricted to innate immunity, because
      at least for the humoral response, all so far detected tumor-specific antibodies
      belong to the natural immunity. In this review we try to explain why malignant
      cells might be "too sweet" to induce a memory.

PMID- 18053199
TI  - Recruitment of young women to a trial of chlamydia screening - as easy as it
      sounds?
AB  - BACKGROUND: Recruiting to trials is complex and difficult. The Prevention of
      Pelvic Infection (POPI) trial aims to see if screening women for chlamydia and
      treating those found to be infected reduces the incidence of pelvic inflammatory
      disease in the following twelve months. It focuses on young, sexually active,
      multiethnic, mainly inner city, female students. The main aim of this paper is to
      describe our recruitment methods. Secondary aims in two small subgroups, are to
      compare characteristics of women recruited with those not recruited, and to
      explore participants' understanding of when their samples would be tested for
      chlamydia. METHODS: Women students attending lectures or in common rooms at 22
      universities and further education colleges were recruited by female research
      assistants working in pairs. Participants were asked to complete a questionnaire
      on sexual health and to provide self-taken vaginal swabs. In addition, during 3
      recruitment sessions, a female medical student asked non-participants to complete
      a brief anonymous questionnaire on reasons for not taking part. Finally another
      female medical student contacted 40 consecutive participants within a month of
      recruitment and asked if they understood that their samples might not be tested
      for a year. RESULTS: With enormous effort over 2 years we recruited 2526 women. A
      survey of 61 non-responders showed only 18 (30%) were eligible to take part (age
      <28, been sexually active and not been tested for chlamydia in the past 3
      months). Eligible non-responders were of similar age to the 35 responders in the
      same recruitment sessions, but more likely to be from ethnic minority groups (67%
      12/18 versus 29% 10/35 p < 0.01). Email and telephone contact with 35/40 (88%) of
      consecutive participants showed only two (6%) did not understand that their
      specimen might not be tested for chlamydia for a year. Thirty participants (85%)
      could name one or more possible consequences of untreated chlamydia infection.
      CONCLUSION: As in other studies, a key to attaining recruitment targets was the
      enthusiasm of the research team. Minority ethnic groups were probably under
      represented, but understanding of participants was good. TRIAL REGISTRATION:
      Clinical Trials NCT 00115388.

PMID- 18053198
TI  - A prospective, randomised, controlled clinical study on the assessment of
      tolerability and of clinical efficacy of Merional (hMG-IBSA) administered
      subcutaneously versus Merional administered intramuscularly in women undergoing
      multifollicular ovarian stimulation in an ART programme (IVF).
AB  - BACKGROUND: Multifollicular ovarian stimulation (MOS) is widely used in IVF and
      the compliance to treatment is deeply influenced by the tolerability of the
      medication(s) used and by the ease of self-administration. This prospective,
      controlled, randomised, parallel group open label, multicenter, phase III,
      equivalence study has been aimed to compare the clinical effectiveness (in terms
      of oocytes obtained) and tolerability of subcutaneous (s.c.) self-administered
      versus classical intramuscular (i.m.) injections of Merional, a new highly
      purified hMG preparation. METHODS: A total of 168 normogonadotropic women
      undergoing IVF were enrolled. Among them, 160 achieved pituitary suppression with
      a GnRH-agonist long protocol and were randomised to MOS treatment with Merional
      s.c. or i.m. They started MOS with a standard hMG dose between 150-300 IU,
      depending upon patient's age, and underwent a standard IVF procedure. RESULTS: No
      statistically significant difference in the mean number of collected oocytes
      (primary endpoint) was observed between the two study subgroups (7.46, SD 4.24
      vs. 7.86, SD 4.28 in the s.c. and i.m. subgroups, respectively). As concerns the
      secondary outcomes, both the pregnancy and the clinical pregnancy rates were
      comparable between subgroups. The incidence of adverse events was similar in the
      two groups (2.4% vs. 3.7%, respectively). Pain at injection site was reported
      only the i.m. group (13.9% of patients). CONCLUSION: Merional may be used by s.c.
      injections in IVF with an effectiveness in terms of retrieved oocytes that is
      equivalent to the one obtained with i.m administration and with a better local
      tolerability. With the limitations due to the sample size af this study, s.c. and
      i.m. administration routes seem to have the same overall safety.

PMID- 18053200
TI  - COPD diagnosis related to different guidelines and spirometry techniques.
AB  - The aim was to compare the diagnosis of COPD among smokers according to different
      international guidelines and to compare the outcome when using slow (SVC) and
      forced vital capacity (FVC). In order to find current smokers a questionnaire was
      sent to persons who had been on sick leave for more than two weeks. Those who
      smoked more than 8 cigarettes per day were invited to perform a spirometry.
      Totally 3,887 spirometries were performed. In this sample 10.2% fulfilled the
      NICE COPD-criteria, 14.0% the GOLD COPD-criteria and 21.7% the ERS COPD criteria.
      The diagnosis according to NICE and GOLD guidelines is based on FVC and in the
      ERS guidelines the best value of either SVC or FVC is used. Thus, substantially
      more subjects with COPD were found when the best of either SVC or FVC was used.
      Forced VC tended to be higher than SVC when lung function was normal and in those
      with mild obstruction prior to bronchodilatation whereas SVC exceeded FVC after
      bronchodilatation in those who had severe bronchial obstruction.The diagnosis of
      COPD is highly depending on which guidelines are used for defining the disease.
      If FVC and not the best of SVC and FVC is used when defining COPD the diagnosis
      will be missed in a substantial number of patients.

PMID- 18053201
TI  - Why the way we consider the body matters - reflections on four bioethical
      perspectives on the human body.
AB  - BACKGROUND: Within the context of applied bioethical reasoning, various
      conceptions of the human body are focused upon by the author in relation to
      normative notions of autonomy. RESULTS: The author begins by descriptively
      exploring some main positions in bioethics from which the "body" is
      conceptualized. Such positions conflict: the body is that which is constitutive
      of the individual's experience and perception, or it is conceived of materially
      or mechanistically; or as a constructed locus, always historically and culturally
      transformed. The author goes on to suggest a methodological approach that
      dialectically considers embodiment from four different perspectives: as bodily
      self-determination, as respect for the bodily unavailability of the other, as
      care for bodily individuality; and lastly, as acknowledgement of bodily
      constituted communities. These four perspectives encompass autonomy in two of its
      main interpretations: as the capability of a person to act independent of
      external forces, and as the moral ideal of pursuing individual wishes by means of
      role distance, self-limitation and universalization. Various bioethical cases are
      utilized to show how the four perspectives on the body can complement one
      another. CONCLUSION: The way we consider the body matters. The author's
      dialectical method allows a premise-critical identification and exploration of
      bioethical problems concerning the body. The method is potentially applicable to
      other bioethical problems.

PMID- 18053202
TI  - Costs of two alternative Salmonella control policies in Finnish broiler
      production.
AB  - BACKGROUND: Costs and benefits of two Salmonella control policies for broiler
      production were described and compared. The control options were the Zoonosis
      Directive 92/117/EC and the more intense strategy, the Finnish Salmonella Control
      Programme (FSCP). METHODS: The comparison included the Salmonella control costs
      in primary and secondary production and the direct and indirect losses due to
      Salmonella infections in humans in 2000. RESULTS: The total annual costs of the
      FSCP were calculated to be 990 400 EUR (0.02 euro/kg broiler meat). The average
      control costs in the broiler production chain were seven times higher with the
      FSCP than with the Zoonosis Directive alone. However, the public health costs
      were 33 times higher with the Zoonosis Directive alone. The value of one
      prevented loss of life per year exceeded the annual control costs of the FSCP.
      CONCLUSION: Due to significant savings in public health costs compared to costs
      of FSCP, the FSCP was found to be economically feasible.

PMID- 18053203
TI  - Frequency and severity of aggressive incidents in acute psychiatric wards in
      Switzerland.
AB  - BACKGROUND: Aggression and violence and negative consequences thereof are a major
      concern in acute psychiatric inpatient care globally. Variations in study
      designs, settings, populations, and data collection methods render comparisons of
      the incidence of aggressive behaviour in high risk settings difficult. OBJECTIVE:
      To describe the frequency and severity of aggressive incidents in acute
      psychiatric wards in the German speaking part of Switzerland. METHODS: We
      conducted a prospective multicentre study on 24 acute admission wards in 12
      psychiatric hospitals in the German speaking part of Switzerland. Aggressive
      incidents were recorded by the revised Staff Observation Aggression Scale (SOAS
      R) and we checked the data collection for underreporting. Our sample comprised
      2344 treatment episodes of 2017 patients and a total of 41'560 treatment days.
      RESULTS: A total of 760 aggressive incidents were registered. We found incidence
      rates per 100 treatment days between 0.60 (95% CI 0.10-1.78) for physical attacks
      and 1.83 (1.70-1.97) for all aggressive incidents (including purely verbal
      aggression). The mean severity was 8.80 +/- 4.88 points on the 22-point SOAS-R
      severity measure; 46% of the purely verbally aggression was classified as severe
      (>/= 9 pts.). 53% of the aggressive incidents were followed by a coercive
      measure, mostly seclusion or seclusion accompanied by medication. In 13% of the
      patients, one ore more incidents were registered, and 6.9% of the patients were
      involved in one ore more physical attack. Involuntary admission (OR 2.2; 1.6
      2.9), longer length of stay (OR 2.7; 2.0-3.8), and a diagnosis of schizophrenia
      (ICH-10 F2) (OR 2.1; 1.5-2.9) was associated with a higher risk for aggressive
      incidents, but no such association was found for age and gender. 38% of the
      incidents were registered within the first 7 days after admission. CONCLUSION:
      Aggressive incidents in acute admission wards are a frequent and serious problem.
      Due to the study design we consider the incidence rates as robust and
      representative for acute wards in German speaking Switzerland, and thus useful as
      reference for comparative and interventional research. Implications for clinical
      practice include the recommendation to extend the systematic risk assessment
      beyond the first days after admission. The study confirms the necessity to
      differentiate between types of aggressive behaviour when reporting and comparing
      incidence-data.

PMID- 18053204
TI  - Technical challenges to surgical clipping of aneurysmal regrowth with coil
      herniation following endovascular treatment - a case report.
AB  - In recent years, technical developments have made endovascular procedures
      attractive therapeutic options and enabled the endovascular surgeon to redefine
      the management of cerebral aneurysms. However, as the number of aneurysms
      undergoing endovascular therapy has grown, so has the number of patients with
      incompletely treated aneurysms who are presenting for further management. In
      cases of failure of endovascular treatment caused by either incomplete occlusion
      or regrowth of the aneurysm, a complementary treatment is often necessary.
      Surgical treatment of these patients is challenging. We present a case of a
      ruptured posterior cerebral artery aneurysm treated initially with endovascular
      coiling that left behind significant residual aneurysmal sac. Regrowth of the
      aneurysm documented on follow-up was treated surgically. At surgery, the coil was
      found to have herniated through the aneurysmal sac into the subarachnoid space,
      and the aneurysm was successfully clipped without removing the coils. We review
      the regrowth of aneurysms following endovascular therapy and potential problems
      and challenges of surgically managing these lesions.

PMID- 18053206
TI  - Ultrasound in the diagnosis of a median neuropathy in the forearm: case report.
AB  - BACKGROUND: Electrodiagnostic studies are traditionally used in the diagnosis of
      focal neuropathies, however they lack anatomical information regarding the nerve
      and its surrounding structures. The purpose of this case is to show that high
      resolution ultrasound used as an adjunct to electrodiagnostic studies may
      complement this lack of information and give insight to the cause. CASE
      PRESENTATION: A 60-year-old male patient sustained a forearm traction injury
      resulting in progressive weakness and functional loss in the first three digits
      of the right hand. High-resolution ultrasound showed the presence of an enlarged
      nerve and a homogenous soft-tissue structure appearing to engulf the nerve. The
      contralateral side was normal. Surgery revealed fibrotic bands emanating from the
      flexor digitorum profundus muscle compressing the median nerve thus confirming
      the ultrasound findings. CONCLUSION: A diagnostically challenging case of median
      neuropathy in the forearm is presented in which high-resolution ultrasound was
      valuable in establishing an anatomic etiology and directing appropriate
      management.

PMID- 18053205
TI  - Impact of light on Hypocrea jecorina and the multiple cellular roles of ENVOY in
      this process.
AB  - BACKGROUND: In fungi, light is primarily known to influence general morphogenesis
      and both sexual and asexual sporulation. In order to expand the knowledge on the
      effect of light in fungi and to determine the role of the light regulatory
      protein ENVOY in the implementation of this effect, we performed a global screen
      for genes, which are specifically effected by light in the fungus Hypocrea
      jecorina (anamorph Trichoderma reesei) using Rapid Subtraction Hybridization
      (RaSH). Based on these data, we analyzed whether these genes are influenced by
      ENVOY and if overexpression of ENVOY in darkness would be sufficient to execute
      its function. RESULTS: The cellular functions of the detected light responsive
      genes comprised a variety of roles in transcription, translation, signal
      transduction, metabolism, and transport. Their response to light with respect to
      the involvement of ENVOY could be classified as follows: (i) ENVOY-mediated
      upregulation by light; (ii) ENVOY-independent upregulation by light; (iii) ENVOY
      antagonized upregulation by light; ENVOY-dependent repression by light; (iv)
      ENVOY-independent repression by light; and (v) both positive and negative
      regulation by ENVOY of genes not responsive to light in the wild-type. ENVOY was
      found to be crucial for normal growth in light on various carbon sources and is
      not able to execute its regulatory function if overexpressed in the darkness.
      CONCLUSION: The different responses indicate that light impacts fungi like H.
      jecorina at several cellular processes, and that it has both positive and
      negative effects. The data also emphasize that ENVOY has an apparently more
      widespread cellular role in this process than only in modulating the response to
      light.

PMID- 18053207
TI  - Open access to novel dual flow chamber technology for in vitro cell
      mechanotransduction, toxicity and pharamacokinetic studies.
AB  - BACKGROUND: A major stumbling block for researchers developing experimental
      models of mechanotransduction is the control of experimental variables, in
      particular the transmission of the mechanical forces at the cellular level. A
      previous evaluation of state of the art commercial perfusion chambers showed that
      flow regimes, applied to impart a defined mechanical stimulus to cells, are
      poorly controlled and that data from studies in which different chambers are
      utilized can not be compared, even if the target stress regimes are comparable.
      METHODS: This study provides a novel chamber design to provide both
      physiologically-based flow regimes, improvements in control of experimental
      variables, as well as ease of use compared to commercial chambers. This novel
      design achieves controlled stresses through five gasket designs and both single-
      and dual-flow regimes. RESULTS: The imparted shear stress within the gasket
      geometry is well controlled. Fifty percent of the entire area of the 10 x 21 mm
      universal gasket (Gasket I, designed to impart constant magnitude shear stresses
      in the center of the chamber where outcome measures are taken), is exposed to
      target stresses. In the 8 mm diameter circular area at the center of the chamber
      (where outcome measures are made), over 92% of the area is exposed to the target
      stress (+/- 2.5%). In addition, other gasket geometries provide specific
      gradients of stress that vary with distance from the chamber inlet. Bench-top
      testing of the novel chamber prototype shows improvements, in the ease of use as
      well as in performance, compared to the other commercial chambers. The design of
      the chamber eliminates flow deviations due to leakage and bubbles and allows
      actual flow profiles to better conform with those predicted in computational
      models. CONCLUSION: The novel flow chamber design provides predictable and well
      defined mechanical forces at the surface of a cell monolayer, showing improvement
      over previously tested commercial chambers. The predictability of the imparted
      stress improves both experiment repeatability as well as the accuracy of inter
      study comparisons. Carefully controlling the stresses on cells is critical in
      effectively mimicking in vivo situations. Overall, the improved perfusion flow
      chamber provides the needed resolution, standardization and in vitro model
      analogous to in vivo conditions to make the step towards greater use in research
      and the opportunity to enter the diagnostic and therapeutic market.

PMID- 18053208
TI  - A new computational approach to analyze human protein complexes and predict novel
      protein interactions.
AB  - We propose a new approach to identify interacting proteins based on gene
      expression data. By using hypergeometric distribution and extensive Monte-Carlo
      simulations, we demonstrate that looking at synchronous expression peaks in a
      single time interval is a high sensitivity approach to detect co-regulation among
      interacting proteins. Combining gene expression and Gene Ontology similarity
      analyses enabled the extraction of novel interactions from microarray datasets.
      Applying this approach to p21-activated kinase 1, we validated alpha-tubulin and
      early endosome antigen 1 as its novel interactors.

PMID- 18053209
TI  - Intermittent preventive treatment for the prevention of malaria during pregnancy
      in high transmission areas.
AB  - Malaria in pregnancy is one of the major causes of maternal morbidity and adverse
      birth outcomes. In high transmission areas, its prevention has recently changed,
      moving from a weekly or bimonthly chemoprophylaxis to intermittent preventive
      treatment (IPTp). IPTp consists in the administration of a single curative dose
      of an efficacious anti-malarial drug at least twice during pregnancy - regardless
      of whether the woman is infected or not. The drug is administered under
      supervision during antenatal care visits. Sulphadoxine-pyrimethamine (SP) is the
      drug currently recommended by the WHO. While SP-IPTp seems an adequate strategy,
      there are many issues still to be explored to optimize it. This paper reviewed
      data on IPTp efficacy and discussed how to improve it. In particular, the
      determination of both the optimal number of doses and time of administration of
      the drug is essential, and this has not yet been done. As both foetal growth and
      deleterious effects of malaria are maximum in late pregnancy women should
      particularly be protected during this period. Monitoring of IPTp efficacy should
      be applied to all women, and not only to primi- and secondigravidae, as it has
      not been definitively established that multigravidae are not at risk for malaria
      morbidity and mortality. In HIV-positive women, there is an urgent need for
      specific information on drug administration patterns (need for higher doses,
      possible interference with sulpha-based prophylaxis of opportunistic infections).
      Because of the growing level of resistance of parasites to SP, alternative drugs
      for IPTp are urgently needed. Mefloquine is presently one of the most attractive
      options because of its long half life, high efficacy in sub-Saharan Africa and
      safety during pregnancy. Also, efforts should be made to increase IPTp coverage
      by improving the practices of health care workers, the motivation of women and
      their perception of malaria complications in pregnancy. Because IPTp is not
      applicable in early pregnancy, which is a period when malaria may also be
      deleterious for women and their offspring, there is a necessity to integrate this
      strategy with other preventive measures which can be applied earlier in pregnancy
      such as insecticide-treated nets.

PMID- 18053210
TI  - Aggregates of bacteriophage 0305phi8-36 seed future growth.
AB  - Lytic bacteriophage 0305phi8-36 forms visually observed aggregates during plaque
      formation. Aggregates intrinsically lower propagation potential. In the present
      study, the following observations indicate that lost propagation potential is
      regained with time: (1) Aggregates sometimes concentrate at the edge of clear
      plaques. (2) A semi-clear ring sometimes forms beyond the plaques. (3) Formation
      of a ring is completely correlated with the presence of aggregates at the same
      angular displacement along the plaque edge. To explain this aggregate-derived
      lowering/raising of propagation potential, the following hypothesis is presented:
      Aggregation/dissociation of bacteriophage of 0305phi8-36 is a selected phenomenon
      that evolved to maintain high host finding rate in a trade-off with maintaining
      high rate of bacteriophage progeny production. This hypothesis explains ringed
      plaque morphology observed for other bacteriophages and predicts that aggregates
      will undergo time-dependent change in structure as propagation potential
      increases. In support, fluorescence microscopy reveals time-dependent change in
      the distance between resolution-limited particles in aggregates.

PMID- 18053211
TI  - Compartmentalization of the gut viral reservoir in HIV-1 infected patients.
AB  - BACKGROUND: Recently there has been an increasing interest and appreciation for
      the gut as both a viral reservoir as well as an important host-pathogen interface
      in human immunodefiency virus type 1 (HIV-1) infection. The gut associated
      lymphoid tissue (GALT) is the largest lymphoid organ infected by HIV-1. In this
      study we examined if different HIV-1 quasispecies are found in different parts of
      the gut of HIV-1 infected individuals. RESULTS: Gut biopsies (esophagus, stomach,
      duodenum and colorectum) were obtained from eight HIV-1 infected preHAART (highly
      active antiretroviral therapy) patients. HIV-1 Nef and Reverse transcriptase (RT)
      encoding sequences were obtained through nested PCR amplification from DNA
      isolated from the gut biopsy tissues. The PCR fragments were cloned and
      sequenced. The resulting sequences were subjected to various phylogenetic
      analyses. Expression of the nef gene and viral RNA in the different gut tissues
      was determined using real-time RT-PCR. Phylogenetic analysis of the Nef protein
      encoding region revealed compartmentalization of viral replication in the gut
      within patients. Viral diversity in both the Nef and RT encoding region varied in
      different parts of the gut. Moreover, increased nef gene expression (p < 0.05)
      and higher levels of viral genome were observed in the colorectum (p < 0.05).
      These differences could reflect an adaptation of HIV-1 to the various tissues.
      CONCLUSION: Our results indicated that different HIV-1 quasispecies populate
      different parts of the gut, and that viral replication in the gut is
      compartmentalized. These observations underscore the importance of the gut as a
      host-pathogen interface in HIV-1 infection.

PMID- 18053213
TI  - Recurrence of hepatitis C virus during leucocytopenia and spontaneous clearance
      after recovery from cytopenia: a case report.
AB  - INTRODUCTION: There is little information about the risk of HCV recurrence in
      immunosuppressed patients. Although the presence of antibodies to HCV and the
      absence of HCV-RNA is usually considered to indicate viral elimination, the virus
      may not be completely eliminated but may be under control of an effective immune
      response. CASE PRESENTATION: A 69 year old man presented with jaundice, elevated
      ALT, AST, lipase and concomitant abdominal pain. He was found to be positive for
      HCV-RNA (genotype 3a) and was diagnosed with acute hepatitis C. Six weeks later
      no HCV-RNA was detected, and the patient was diagnosed with hyperthyreosis and
      started on propylthiouracil. After 4 weeks of propylthiouracil treatment, the
      patient developed leucocytopenia, followed by liver function deterioration and
      reappearance of HCV-RNA. Propylthiouracil was discontinued and his leukocyte
      counts increased. Twenty-eight weeks after onset of acute hepatitis C, no HCV-RNA
      was detected. CONCLUSION: This case history shows the risk of recurrence of HCV
      during leucocytopenia. These findings indicate that patients who are anti-HCV
      positive but HCV-RNA negative may be at risk of cytopenia-induced HCV
      reactivation.

PMID- 18053212
TI  - Validity and reliability of the Spanish version of the DN4 (Douleur Neuropathique
      4 questions) questionnaire for differential diagnosis of pain syndromes
      associated to a neuropathic or somatic component.
AB  - BACKGROUND: This study assesses the validity and reliability of the Spanish
      version of DN4 questionnaire as a tool for differential diagnosis of pain
      syndromes associated to a neuropathic (NP) or somatic component (non-neuropathic
      pain, NNP). METHODS: A study was conducted consisting of two phases: cultural
      adaptation into the Spanish language by means of conceptual equivalence,
      including forward and backward translations in duplicate and cognitive
      debriefing, and testing of psychometric properties in patients with NP
      (peripheral, central and mixed) and NNP. The analysis of psychometric properties
      included reliability (internal consistency, inter-rater agreement and test-retest
      reliability) and validity (ROC curve analysis, agreement with the reference
      diagnosis and determination of sensitivity, specificity, and positive and
      negative predictive values in different subsamples according to type of NP).
      RESULTS: A sample of 164 subjects (99 women, 60.4%; age: 60.4 +/- 16.0 years), 94
      (57.3%) with NP (36 with peripheral, 32 with central, and 26 with mixed pain) and
      70 with NNP was enrolled. The questionnaire was reliable [Cronbach's alpha
      coefficient: 0.71, inter-rater agreement coefficient: 0.80 (0.71-0.89), and test
      retest intra-class correlation coefficient: 0.95 (0.92-0.97)] and valid for a cut
      off value > or = 4 points, which was the best value to discriminate between NP
      and NNP subjects. DISCUSSION: This study, representing the first validation of
      the DN4 questionnaire into another language different than the original, not only
      supported its high discriminatory value for identification of neuropathic pain,
      but also provided supplemental psychometric validation (i.e. test-retest
      reliability, influence of educational level and pain intensity) and showed its
      validity in mixed pain syndromes.

PMID- 18053214
TI  - Cardiac functional stress imaging: a sequential approach with stress echo and
      cardiovascular magnetic resonance.
AB  - AIMS: The aim of the study was to assess the feasibility and accuracy of an
      integrated stress imaging algorithm with echo first and second-line Cardiac
      Magnetic Resonance (CMR) in selected cases. Stress echo (SE) is widely used for
      non-invasive diagnosis of coronary artery disease (CAD), but difficult patients
      and ambiguous responses may be met even with top-level technology and expertise.
      CMR might ideally complement SE in well-selected cases with unfeasible and/or
      ambiguous and/or submaximal results. METHODS AND RESULTS: 152 in-hospital
      patients with chest pain and normal baseline function were referred for SE and
      coronary angiography. Of the initial population, 33 were shunted to CMR due to
      poor acoustic window or ambiguous or submaximal SE test. The only criterion of
      positivity for both techniques was the presence of regional wall motion
      abnormalities in at least 2 contiguous segments. Coronary angiography was
      performed independently of test results. Significant CAD was identified by a >50%
      quantitatively assessed diameter reduction in at least 1 major coronary
      vessel.CAD was present in 88 patients. Interpretable and diagnostic stress test
      were obtained in 143 patients with the sequential algorithm. The sequential (SE
      in 110 + CMR in 33 patients) algorithm showed a sensitivity of 76% (95% CI 66% to
      85%) specificity of 87% (95% CI 76% to 95%) and accuracy of 80% (95% CI 73% to
      86%). CONCLUSION: A sequential functional stress imaging algorithm with stress
      echo first and stress CMR in selected cases is feasible, clinically realistic and
      allows an efficient, radiation-free diagnosis of CAD.

PMID- 18053215
TI  - Applying the scientific method when assessing the influence of migratory birds on
      the dispersal of H5N1.
AB  - BACKGROUND: The role of wild birds in the dispersal of highly pathogenic avian
      influenza virus H5N1 continues to be the subject of considerable debate. However,
      some researchers functionally examining the same question are applying opposing
      null hypotheses when examining this issue. DISCUSSION: I describe the correct
      method for establishing a null hypothesis under the scientific method. I suggest
      that the correct null hypothesis is that migratory birds can disperse this virus
      during migration and encourage researchers to design studies to falsify this
      null. Finally, I provide several examples where statements made during this
      debate, while strictly true, are not generally informative or are speculative.
      SUMMARY: By adhering to the scientific method, definitive answers regarding the
      role of wild birds in the dispersal of highly pathogenic viruses will be reached
      more effectively.

PMID- 18053216
TI  - Effects of stimulus-driven synchronization on sensory perception.
AB  - BACKGROUND: A subject's ability to differentiate the loci of two points on the
      skin depends on the stimulus-evoked pericolumnar lateral inhibitory interactions
      which increase the spatial contrast between regions of SI cortex that are
      activated by stimulus-evoked afferent drive. Nevertheless, there is very little
      known about the impact that neuronal interactions - such as those evoked by
      mechanical skin stimuli that project to and coordinate synchronized activity in
      adjacent and/or near-adjacent cortical columns - could have on sensory
      information processing. METHODS: The temporal order judgment (TOJ) and temporal
      discriminative threshold (TDT) of 20 healthy adult subjects were assessed both in
      the absence and presence of concurrent conditions of tactile stimulation. These
      measures were obtained across a number of paired sites - two unilateral and one
      bilateral - and several conditions of adapting stimuli were delivered both prior
      to and concurrently with the TOJ and TDT tasks. The pairs of conditioning stimuli
      were synchronized and periodic, synchronized and non-periodic, or asynchronous
      and non-periodic. RESULTS: In the absence of any additional stimuli, TOJ and TDT
      results obtained from the study were comparable across a number of pairs of
      stimulus sites - unilateral as well as bilateral. In the presence of a 25 Hz
      conditioning sinusoidal stimulus which was delivered both before, concurrently
      and after the TOJ task, there was a significant change in the TOJ measured when
      the two stimuli were located unilaterally on digits 2 and 3. However, in the
      presence of the same 25 Hz conditioning stimulus, the TOJ obtained when the two
      stimuli were delivered bilaterally was not impacted. TDT measures were not
      impacted to the same degree by the concurrent stimuli that were delivered to the
      unilateral or bilateral stimulus sites. This led to the speculation that the
      impact that the conditioning stimuli - which were sinusoidal, periodic and
      synchronous - had on TOJ measures was due to the synchronization of adjacent
      cortical ensembles in somatosensory cortex, and that the synchronization of these
      cortical ensembles could have been responsible for the degradation in temporal
      order judgment. In order to more directly test this hypothesis, the synchronized
      25 Hz conditioning stimuli that were delivered during the initial TOJ test were
      replaced with asynchronous non-periodic 25 Hz conditioning stimuli, and these
      asynchronous conditioning stimuli did not impact the TOJ measures. CONCLUSION:
      The results give support to the theory that synchronization of cortical ensembles
      in SI could significantly impact the topography of temporal perception, and these
      findings are speculated to be linked mechanistically to previously reported co
      activation plasticity studies. Additionally, the impact that such synchronizing
      conditioning stimuli have on TOJ - which can be measured relatively quickly -
      could provide an effective means to assess the functional connectivity of
      neurologically compromised subject populations.

PMID- 18053217
TI  - Perceived community environment and physical activity involvement in a northern
      rural Aboriginal community.
AB  - BACKGROUND: Type 2 diabetes disproportionately affects Aboriginal peoples in
      Canada. Ample evidence shows that regular physical activity (PA) plays an
      important role in the prevention and treatment of type 2 diabetes. Evidence is
      beginning to emerge linking PA to the physical environment but little is known
      about the relationship between remote rural environments and PA involvement in
      Aboriginal peoples. This study's purpose was to investigate the relationship
      between perceptions of the environment and PA and walking patterns in Aboriginal
      adults in order to inform the planning and implementation of community-relevant
      PA interventions. METHODS: Two hundred and sixty three residents (133 women, mean
      age = 35.6 years, SD = 12.3 and 130 men, mean age = 37.2 years, SD = 13.1) from
      Moose Factory, Ontario were asked about environmental factors related to walking
      and PA involvement. Survey items were drawn from standardized, validated
      questionnaires. Descriptive statistics (means, standard deviations, percentages)
      were calculated. A series of hierarchical multiple regressions were performed to
      determine associations between walking and overall PA with perceived
      environmental variables. RESULTS: Hierarchical multiple regression to predict
      walking revealed significant associations between walking and perceived safety
      and aesthetics. Owning home exercise equipment predicted strenuous PA. Different
      aspects of the physical environment appear to influence different types of
      physical activities. The significant amount of variance in behaviour accounted
      for by perceived environmental variables (5.3% walking) included safety,
      aesthetics, convenience, owning home exercise equipment and comfortable shoes for
      walking. CONCLUSION: Results suggest that a supportive physical environment is
      important for PA involvement and that walking and activities of different
      intensity appear to be mediated by different perceived environmental variables.
      Implications for PA promotion in rural environments where Aboriginal people face
      many unique environmental features (e.g., bears, mosquitoes, extreme cold) are
      discussed.

PMID- 18053218
TI  - Hematochezia in a patient with liver cirrhosis.
AB  - Although commonly detectable in patients with cirrhosis, rectal varices only
      infrequently cause significant hematochezia (0.5-3.6%). While they may be
      expected to resolve with treatment of the concomitant portal hypertension, there
      is currently no standardized approach to their management in isolation. Therefore
      many authorities recommend transjugular intrahepatic portosystemic shunting
      (TIPS) as a means of alleviating otherwise recalcitrant bleeding. Conceptually,
      however, rectal varices should be as amenable to local therapies as are their
      counterparts occurring at the esophagogastric junction. In this report, we
      describe the use of endoscopic banding per ano to alleviate significant rectal
      bleeding in a patient with poorly controlled portal hypertension. This allowed
      medical optimisation so that the underlying pathology could be controlled without
      recourse to TIPS or other means of creating a formal portosystemic shunt.

PMID- 18053219
TI  - Correlates of current cigarette smoking among in-school adolescents in the
      Kurdistan region of Iraq.
AB  - BACKGROUND: Many adult cigarette smokers initiated the habit as adolescents.
      Adolescent tobacco use may be a marker of other unhealthy behaviours. There are
      limited data on the prevalence and correlates of cigarette smoking among in
      school adolescents in Iraq. We aimed to estimate the prevalence of, and assess
      the socio-demographic correlates of current cigarette smoking among in-school
      adolescents in Kurdistan region of Iraq. METHODS: Secondary data analysis of the
      Global Youth Tobacco Survey, conducted in the region of Kurdistan, Iraq in 2006.
      Logistic regression analysis was conducted to assess the association between
      current cigarette smoking and explanatory variables. RESULTS: One thousand nine
      hundred eighty-nine adolescents participated in the Kurdistan-Iraq Global Youth
      Tobacco Survey. Of these, 58.1% and 41.9% were boys and girls respectively. The
      overall prevalence of current cigarette smoking was 15.3%; 25.1% and 2.7% in boys
      and girls respectively. The factors associated with adolescent smoking were:
      parents' smoking, smoking in closest friends, male gender, having pocket money
      and perceptions that boys or girls who smoked were attractive. CONCLUSION: We
      suggest that public health interventions aimed to curb adolescent cigarette
      smoking should be designed, implemented and evaluated with due recognition to the
      factors that are associated with the habit.

PMID- 18053220
TI  - Pioglitazone is as effective as dexamethasone in a cockroach allergen-induced
      murine model of asthma.
AB  - BACKGROUND: While glucocorticoids are currently the most effective therapy for
      asthma, associated side effects limit enthusiasm for their use. Peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) activators include the
      synthetic thiazolidinediones (TZDs) which exhibit anti-inflammatory effects that
      suggest usefulness in diseases such as asthma. How the ability of TZDs to
      modulate the asthmatic response compares to that of glucocorticoids remains
      unclear, however, because these two nuclear receptor agonists have never been
      studied concurrently. Additionally, effects of PPAR-gamma agonists have never
      been examined in a model involving an allergen commonly associated with human
      asthma. METHODS: We compared the effectiveness of the PPAR-gamma agonist
      pioglitazone (PIO) to the established effectiveness of a glucocorticoid receptor
      agonist, dexamethasone (DEX), in a murine model of asthma induced by cockroach
      allergen (CRA). After sensitization to CRA and airway localization by intranasal
      instillation of the allergen, Balb/c mice were challenged twice at 48-h intervals
      with intratracheal CRA. Either PIO (25 mg/kg/d), DEX (1 mg/kg/d), or vehicle was
      administered throughout the period of airway CRA exposure. RESULTS: PIO and DEX
      demonstrated similar abilities to reduce airway hyperresponsiveness, pulmonary
      recruitment of inflammatory cells, serum IgE, and lung levels of IL-4, IL-5, TNF
      alpha, TGF-beta, RANTES, eotaxin, MIP3-alpha, Gob-5, and Muc5-ac. Likewise,
      intratracheal administration of an adenovirus containing a constitutively active
      PPAR-gamma expression construct blocked CRA induction of Gob-5 and Muc5-ac.
      CONCLUSION: Given the potent effectiveness shown by PIO, we conclude that PPAR
      gamma agonists deserve investigation as potential therapies for human asthma.

PMID- 18053221
TI  - Impact of estrogen receptor gene polymorphisms and mRNA levels on obesity and
      lipolysis--a cohort study.
AB  - BACKGROUND: The estrogen receptors alpha and beta (ESR1, ESR2) have been
      implicated in adiposity, lipid metabolism and feeding behaviour. In this report
      we analyse ESR1 and ESR2 gene single nucleotide polymorphisms (SNPs) for
      association with obesity. We also relate adipose tissue ESR1 mRNA levels and ESR1
      SNPs to adipocyte lipolysis and lipogenesis phenotypes. METHODS: 23 ESR1 and 11
      ESR2 tag-SNPs, covering most of the common haplotype variation in each gene
      according to HAPMAP data, were analysed by Chi2 for association with obesity in a
      cohort comprising 705 adults with severe obesity and 402 lean individuals.
      Results were replicated in a cohort comprising 837 obese and 613 lean subjects.
      About 80% of both cohorts comprised women and 20% men. Adipose tissue ESR1 mRNA
      was quantified in 122 women and related to lipolysis and lipogenesis by multiple
      regression. ESR1 SNPs were analysed for association with adipocyte lipolysis and
      lipogenesis phenotypes in 204 obese women by simple regression. RESULTS: No ESR1
      SNP was associated with obesity. Five ESR2 SNPs displayed nominal significant
      allelic association with obesity in women and one in men. The two ESR2 SNPs
      associated with obesity with nominal P value < 0.01 were genotyped in a second
      cohort where no association with obesity was observed. There was an inverse
      correlation between ESR1 mRNA levels in abdominal subcutaneous (sc) adipose
      tissue and basal lipolysis, as well as responsiveness to adrenoceptor agonists
      independent of age and BMI (P value 0.009-0.045). ESR1 rs532010 was associated
      with lipolytic sensitivity to noradrenaline (nominal P value 0.012), and ESR1
      rs1884051 with responsiveness to the non-selective beta-adrenoceptor agonist
      isoprenaline (nominal P value 0.05). These associations became non-significant
      after Bonferroni correction. CONCLUSION: ESR1 gene alleles are unlikely to be a
      major cause of obesity in women. A minor importance of ESR2 on severe obesity
      cannot be excluded. The inverse correlation between ESR1 mRNA levels and
      lipolytic responsiveness to adrenoceptor agonists implies that low adipose tissue
      ESR1 levels attenuate catecholamine resistance in sc fat cells of obese women
      hereby contributing to loss of sc and gain of visceral fat. There is no evidence
      for a genetic impact of ESR1 on lipolysis or lipogenesis.

PMID- 18053222
TI  - GSTM1 and APE1 genotypes affect arsenic-induced oxidative stress: a repeated
      measures study.
AB  - BACKGROUND: Chronic arsenic exposure is associated with an increased risk of
      skin, bladder and lung cancers. Generation of oxidative stress may contribute to
      arsenic carcinogenesis. METHODS: To investigate the association between arsenic
      exposure and oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was
      evaluated in a cohort of 97 women recruited from an arsenic-endemic region of
      Bangladesh in 2003. Arsenic exposure was measured in urine, toenails, and
      drinking water. Drinking water and urine samples were collected on three
      consecutive days. Susceptibility to oxidative stress was evaluated by genotyping
      relevant polymorphisms in glutathione-s transferase mu (GSTM1), human 8
      oxoguanine glycosylase (hOGG1) and apurinic/apyrimidinic endonuclease (APE1)
      genes using the Taqman method. Data were analyzed using random effects Tobit
      regression to account for repeated measures and 8-OHdG values below the detection
      limit. RESULTS: A consistent negative effect for APE1 was observed across water,
      toenail and urinary arsenic models. APE1 148 glu/glu + asp/glu genotype was
      associated with a decrease in logged 8-OHdG of 0.40 (95%CI -0.73, -0.07) compared
      to APE1 148 asp/asp. An association between total urinary arsenic and 8-OHdG was
      observed among women with the GSTM1 null genotype but not in women with GSTM1
      positive. Among women with GSTM1 null, a comparison of the second, third, and
      fourth quartiles of total urinary arsenic to the first quartile resulted in a
      0.84 increase (95% CI 0.27, 1.42), a 0.98 increase (95% CI 033, 1.66) and a 0.85
      increase (95% CI 0.27, 1.44) in logged 8-OHdG, respectively. No effects between 8
      OHdG and toenail arsenic or drinking water arsenic were observed. CONCLUSION:
      These results suggest the APE1 variant genotype decreases repair of 8-OHdG and
      that arsenic exposure is associated with oxidative stress in women who lack a
      functional GSTM1 detoxification enzyme.

PMID- 18053223
TI  - Trafficking of central opioid receptors and descending pain inhibition.
AB  - The delta-opioid receptor (DOR) belongs to the superfamily of G-protein-coupled
      receptors (GPCRs) with seven transmembrane domains, and its membrane trafficking
      is regulated by intracellular sorting processes involving its C-tail motifs,
      intracellular sorting proteins, and several intracellular signaling pathways. In
      the quiescent state, DOR is generally located in the intracellular compartments
      in central neurons. However, chronic stimulation, such as chronic pain and
      sustained opioid exposure, may induce membrane trafficking of DOR and its
      translocation to surface membrane. The emerged functional DOR on cell membrane is
      actively involved in pain modulation and opioid analgesia. This article reviews
      current understanding of the mechanisms underlying GPCRs and DOR membrane
      trafficking, and the analgesic function of emerged DOR through membrane
      trafficking under certain pathophysiological circumstances.

PMID- 18053224
TI  - Phylogenetic analysis of Shiga toxin 1 and Shiga toxin 2 genes associated with
      disease outbreaks.
AB  - BACKGROUND: Shiga toxins 1 and 2 (Stx1 and Stx2) are bacteriophage-encoded
      proteins that have been associated with hemorrhagic colitis, hemolytic uremic
      syndrome and other severe disease conditions. Stx1 and Stx2 are genetically and
      immunologically distinct but share the same compound toxin structure, method of
      entry and enzymatic function. RESULTS: Phylogenetic analysis was performed using
      Stx1 and Stx2 amino acid and nucleotide sequences from 41 strains of Escherichia
      coli, along with known stx sequences available from GenBank. The analysis
      confirmed the Stx1 and Stx2 divergence, and showed that there is generally more
      sequence variation among stx2 genes than stx1. The phylograms showed generally
      flat topologies among our strains' stx1 and stx2 genes. In the stx2 gene, 39.5%
      of the amino acid sites display very low nonsynonymous to synonymous substitution
      ratios. CONCLUSION: The stx1 and stx2 genes used in this phylogenetic study show
      sequence conservation with no significant divergence with respect to place or
      time. These data could indicate that Shiga toxins are experiencing purifying
      selection.

PMID- 18053225
TI  - How is childhood development of immunity to Plasmodium falciparum enhanced by
      certain antimalarial interventions?
AB  - The development of acquired protective immunity to Plasmodium falciparum
      infection in young African children is considered in the context of three current
      strategies for malaria prevention: insecticide-impregnated bed nets or curtains,
      anti-sporozoite vaccines and intermittent preventive therapy. Evidence is
      presented that each of these measures may permit attenuated P. falciparum blood
      stage infections, which do not cause clinical malaria but can act as an effective
      blood-stage "vaccine". It is proposed that the extended serum half-life, and
      rarely considered liver-stage prophylaxis provided by the anti-folate combination
      sulphadoxine-pyrimethamine frequently lead to such attenuated infections in high
      transmission areas, and thus contribute to the sustained protection from malaria
      observed among children receiving the combination as intermittent preventative
      therapy or for parasite clearance in vaccine trials.

PMID- 18053226
TI  - Giant cutaneous horn in an African woman: a case report.
AB  - INTRODUCTION: A cutaneous horn is a conical projection of hyperkeratotic
      epidermis. Though grossly resembling an animal horn, it lacks a bony core. These
      lesions have been well described in Caucasian patients, as well as in a number of
      Arabic and Asian patients. CASE PRESENTATION: A young female presented with a
      large 'horn' of five-year duration, arising from a burn scar. Excision and scalp
      reconstruction were performed. Histology was reported as verrucoid epidermal
      hyperplasia with cutaneous horn. CONCLUSION: This may be the first documentation
      of this lesion in a black African. Although likely rare, it should be considered
      in the differential diagnosis of dermatologic lesions. Up to 40% of cutaneous
      horns occur as part of a premalignant or malignant lesion, and surgical
      extirpation with histological examination is thus more important than the
      curiosity surrounding these lesions.

PMID- 18053227
TI  - Bullet-induced synovitis as a cause of secondary osteoarthritis of the hip joint:
      A case report and review of literature.
AB  - BACKGROUND: With increasing prevalence of gunshot injuries we are seeing more
      patients with retained bullet fragments lodged in their bodies. Embedded lead
      bullets are usually considered inert after their kinetic energy has dissipated
      hence these are not removed routinely. However, exposure of any foreign body to
      synovial fluid may lead to rapid degradation and hence result in systemic
      absorption, causing local and systemic symptoms. We present the case of a thirty
      year old man who came to our out patient department with a history of
      progressive, severe hip pain ten years after a gun shot injury to his right hip.
      CONCLUSION: The common belief that intraarticular bullets should not be removed
      has no benefit and may result in unwanted long term complications.

PMID- 18053228
TI  - Aspects of statin prescribing in Norwegian counties with high, average and low
      statin consumption - an individual-level prescription database study.
AB  - BACKGROUND: A previous study has shown that variations in threshold and intensity
      (lipid goal attainment) of statins for primary prevention contribute to regional
      differences in overall consumption of statins in Norway. Our objective was to
      explore how differences in prevalences of use, dosing characteristics, choice of
      statin and continuity of therapy in individual patients adds new information to
      previous results. METHODS: Data were retrieved from The Norwegian Prescription
      Database. We included individuals from counties with high, average, and low
      statin consumption, who had at least one statin prescription dispensed during
      2004 (N = 40 143).1-year prevalence, prescribed daily dose (PDD), statin of
      choice, and continuity of therapy assessed by mean number of tablets per day.
      RESULTS: The high-consumption county had higher prevalence of statin use in all
      age groups. Atorvastatin and simvastatin were dispensed in 79-87% of all statin
      users, and the proportion was significantly higher in the high-consumption
      county. The estimated PDDs were higher than the DDDs, up to twice the DDD for
      atorvastatin. The high-consumption county had the highest PDD for simvastatin
      (25.9 mg) and atorvastatin (21.9 mg), and more users received tablets in the
      upper range of available strengths. Continuity of therapy was similar in the
      three counties. CONCLUSION: Although differences in age-distribution seems to be
      an important source of variation in statin consumption, it cannot account for the
      total variation between counties in Norway. Variations in prevalences of use, and
      treatment intensity in terms of PDD and choice of statin also affect the total
      consumption. The results in this study seems to correspond to previous findings
      of more frequent statin use in primary prevention, and more statin users
      achieving lipid goal in the highest consuming county.

PMID- 18053229
TI  - Topical latanoprost causes posterior movement of lens in a patient with
      exfoliation syndrome and subluxated lens: a case report.
AB  - INTRODUCTION: To report the effect of topical latanoprost on the position of a
      subluxated lens. CASE PRESENTATION: After 0.005% latanoprost was administered
      topically to a patient with ocular hypertension due to a pseudoexfoliation
      syndrome and a subluxated lens, the position of the lens was examined by slit
      lamp biomicroscopy, and the ciliary body thickness by ultrasound biomicroscopy.
      The lens had moved posteriorly, and the thickness of the ciliary body had
      decreased after the latanoprost. CONCLUSION: We suggest that the decrease in the
      thickness of the ciliary body resulted in an increase in the tension of the
      zonule of Zinn fibers, thus pulling the subluxated lens posteriorly.

PMID- 18053231
TI  - 'It gives you an understanding you can't get from any book.' The relationship
      between medical students' and doctors' personal illness experiences and their
      performance: a qualitative and quantitative study.
AB  - BACKGROUND: Anecdotes abound about doctors' personal illness experiences and the
      effect they have on their empathy and care of patients. We formally investigated
      the relationship between doctors' and medical students' personal illness
      experiences, their examination results, preparedness for clinical practice,
      learning and professional attitudes and behaviour towards patients. METHODS:
      Newly-qualified UK doctors in 2005 (n = 2062/4784), and two cohorts of students
      at one London medical school (n = 640/749) participated in the quantitative arm
      of the study. 37 Consultants, 1 Specialist Registrar, 2 Clinical Skills Tutors
      and 25 newly-qualified doctors participated in the qualitative arm. Newly
      qualified doctors and medical students reported their personal illness
      experiences in a questionnaire. Doctors' experiences were correlated with self
      reported preparedness for their new clinical jobs. Students' experiences were
      correlated with their examination results, and self-reported anxiety and
      depression. Interviews with clinical teachers, newly-qualified doctors and senior
      doctors qualitatively investigated how personal illness experiences affect
      learning, professional attitudes, and behaviour. RESULTS: 85.5% of newly
      qualified doctors and 54.4% of medical students reported personal illness
      experiences. Newly-qualified doctors who had been ill felt less prepared for
      starting work (p < 0.001), but those who had only experienced illness in a
      relative or friend felt more prepared (p = 0.02). Clinical medical students who
      had been ill were more anxious (p = 0.01) and had lower examination scores (p =
      0.006). Doctors felt their personal illness experiences helped them empathise and
      communicate with patients. Medical students with more life experience were
      perceived as more mature, empathetic, and better learners; but illness at medical
      school was recognised to impede learning. CONCLUSION: The majority of the medical
      students and newly qualified doctors we studied reported personal illness
      experiences, and these experiences were associated with lower undergraduate
      examination results, higher anxiety, and lower preparedness. However reflection
      on such experiences may have improved professional attitudes such as empathy and
      compassion for patients. Future research is warranted in this area.

PMID- 18053230
TI  - Prediction of synergistic transcription factors by function conservation.
AB  - BACKGROUND: Previous methods employed for the identification of synergistic
      transcription factors (TFs) are based on either TF enrichment from co-regulated
      genes or phylogenetic footprinting. Despite the success of these methods, both
      have limitations. RESULTS: We propose a new strategy to identify synergistic TFs
      by function conservation. Rather than aligning the regulatory sequences from
      orthologous genes and then identifying conserved TF binding sites (TFBSs) in the
      alignment, we developed computational approaches to implement the novel strategy.
      These methods include combinatorial TFBS enrichment utilizing distance
      constraints followed by enrichment of overlapping orthologous genes from human
      and mouse, whose regulatory sequences contain the enriched TFBS combinations.
      Subsequently, integration of function conservation from both TFBS and overlapping
      orthologous genes was achieved by correlation analyses. These techniques have
      been used for genome-wide promoter analyses, which have led to the identification
      of 51 homotypic TF combinations; the validity of these approaches has been
      exemplified by both known TF-TF interactions and function coherence analyses. We
      further provide computational evidence that our novel methods were able to
      identify synergistic TFs to a much greater extent than phylogenetic footprinting.
      CONCLUSION: Function conservation based on the concordance of combinatorial TFBS
      enrichment along with enrichment of overlapping orthologous genes has been proven
      to be a successful means for the identification of synergistic TFs. This approach
      avoids the limitations of phylogenetic footprinting as it does not depend upon
      sequence alignment. It utilizes existing gene annotation data, such as those
      available in GO, thus providing an alternative method for functional TF discovery
      and annotation.

PMID- 18053232
TI  - Analgesics use and ESRD in younger age: a case-control study.
AB  - BACKGROUND: An ad hoc peer-review committee was jointly appointed by Drug
      Authorities and Industry in Germany, Austria and Switzerland in 1999/2000 to
      review the evidence for a causal relation between phenacetin-free analgesics and
      nephropathy. The committee found the evidence as inconclusive and requested a new
      case-control study of adequate design. METHODS: We performed a population-based
      case-control study with incident cases of end-stage renal disease (ESRD) under
      the age of 50 years and four age and sex-matched neighborhood controls in 170
      dialysis centers (153 in Germany, and 17 in Austria) from January 1, 2001 to
      December 31, 2004. Data on lifetime medical history, risk factors, treatment, job
      exposure and intake of analgesics were obtained in a standardized face-to-face
      interview using memory aids to enhance accuracy. Study design, study performance,
      analysis plan, and study report were approved by an independent international
      advisory committee and by the Drug Authorities involved. Unconditional logistic
      regression analyses were performed. RESULTS: The analysis included 907 cases and
      3,622 controls who had never used phenacetin-containing analgesics in their
      lifetime. The use of high cumulative lifetime dose (3rd tertile) of analgesics in
      the period up to five years before dialysis was not associated with later ESRD.
      Adjusted odds ratios with 95% confidence intervals were 0.8 (0.7 - 1.0) and 1.0
      (0.8 - 1.3) for ever- compared with no or low use and high use compared with low
      use, respectively. The same results were found for all analgesics and for mono-,
      and combination preparations with and without caffeine. No increased risk was
      shown in analyses stratifying for dose and duration. Dose-response analyses
      showed that analgesic use was not associated with an increased risk for ESRD up
      to 3.5 kg cumulative lifetime dose (98 % of the cases with ESRD). While the large
      subgroup of users with a lifetime dose up to 0.5 kg (278 cases and 1365 controls)
      showed a significantly decreased risk, a tiny subgroup of extreme users with over
      3.5 kg lifetime use (19 cases and 11 controls) showed a significant risk
      increase. The detailed evaluation of 22 cases and 19 controls with over 2.5 kg
      lifetime use recommended by the regulatory advisors showed an impressive excess
      of other conditions than analgesics triggering the evolution of ESRD in cases
      compared with controls. CONCLUSION: We found no clinically meaningful evidence
      for an increased risk of ESRD associated with use of phenacetin-free analgesics
      in single or combined formulation. The apparent risk increase shown in a small
      subgroup with extreme lifetime dose of analgesics is most likely an indirect, non
      causal association. This hypothesis, however, cannot be confirmed or refuted
      within our case-control study. Overall, our results lend support to the mounting
      evidence that phenacetin-free analgesics do not induce ESRD and that the notion
      of "analgesic nephropathy" needs to be re-evaluated.

PMID- 18053234
TI  - Being 40 or younger is an independent risk factor for relapse in operable breast
      cancer patients: the Saudi Arabia experience.
AB  - BACKGROUND: Breast cancer in young Saudi women is a crucial problem. According to
      the 2002 annual report of Saudi National Cancer Registry, breast cancers that
      developed before the age of 40 comprise 26.4% of all female breast cancers
      comparing to 6.5% in the USA. Breast cancer in young patients is often associated
      with a poorer prognosis, but there has been a scarcity of published data in the
      Middle East population. METHODS: Total of 867 breast cancer patients seen at King
      Faisal Specialist Hospital & Research Centre (KFSH&RC) between 1986 and 2002 were
      reviewed. Patients were divided in two age groups: < or = 40 years and above 40
      years. The clinicopathological characteristics and treatment outcomes were
      compared between younger and older age groups. RESULTS: Median age at
      presentation was 45 years. A total of 288 (33.2%) patients were aged < or = 40
      years. Hormone receptors were positive in 69% of patients 40 and 78.2% of
      patients above 40 (p = 0.009). There was a significantly higher incidence of
      grade III tumor in younger patients compared to older patients (p = 0.0006).
      Stage, tumor size, lymphatic/vascular invasion, number of nodes and axillary
      lymph node status, did not differ significantly between the two age groups.
      Younger patients had a greater probability of recurrence at all time periods (p =
      0.035). Young age had a negative impact on survival of patients with positive
      axillary lymph nodes (p = 0.030) but not on survival of patients with negative
      lymph nodes (p = 0.695). Stage, tumor size, nodal status and hormonal receptors
      had negative impact on survival. Adjuvant chemotherapy was administered to 87.9%
      of younger and 65.6% of older patients (p < 0.0001). In terms of hormone therapy,
      the proportion of tamoxifen treated patients was significantly lower in young age
      group (p < 0.0001). No significant difference in radiation therapy between the
      two groups. CONCLUSION: Young age (< or = 40) is an independent risk factor for
      relapse in operable Saudi breast cancer patients. The fundamental biology of
      young age breast cancer patients needs to be elucidated.

PMID- 18053233
TI  - Clinical protection against caprine herpesvirus 1 genital infection by intranasal
      administration of a live attenuated glycoprotein E negative bovine herpesvirus 1
      vaccine.
AB  - BACKGROUND: Caprine herpesvirus 1 (CpHV-1) is responsible of systemic diseases in
      kids and genital diseases leading to abortions in goats. CpHV-1 is widespread and
      especially in Mediterranean countries as Greece, Italy and Spain. CpHV-1 is
      antigenically and genetically closely related to bovine herpesvirus 1 (BoHV-1).
      Taking into account the biological properties shared by these two viruses, we
      decided in the current study to assess the protection of a live attenuated
      glycoprotein E (gE) negative BoHV-1 vaccine against a genital CpHV-1 infection in
      goats. RESULTS: The vaccine was inoculated intranasally twice three weeks apart
      followed by a subsequent CpHV-1 intravaginal challenge which is the natural route
      of infection in three goats. To analyse the safety and the efficacy of this
      marker vaccine, two groups of three goats served as controls: one immunised with
      a virulent CpHV-1 and one uninoculated until the challenge. Goats were clinically
      monitored and all sampling procedures were carried out in a blind manner. The
      vaccine did not induce any undesirable local or systemic reaction and goats did
      not excrete gE-negative BoHV-1. After challenge, a significant reduction in
      disease severity was observed in immunised goats. Moreover, goats immunised with
      either gE-negative BoHV-1 or CpHV-1 exhibited a significant reduction in the
      length and the peak of viral excretion. Antibodies neutralising both BoHV-1 and
      CpHV-1 were raised in immunised goats. CONCLUSION: Intranasal application of a
      live attenuated gE-negative BoHV-1 vaccine is able to afford a clinical
      protection and a reduction of virus excretion in goats challenged by a CpHV-1
      genital infection.

PMID- 18053235
TI  - Incudomalleal joint formation: the roles of apoptosis, migration and
      downregulation.
AB  - BACKGROUND: The middle ear of mammals is composed of three endochondrial
      ossicles, the stapes, incus and malleus. Joints link the malleus to the incus and
      the incus to the stapes. In the mouse the first arch derived malleus and incus
      are formed from a single Sox9 and Type II collagen expressing condensation that
      later subdivides to give rise to two separate ossicles. In contrast the stapes
      forms from a separate condensation derived from the second branchial arch. Fusion
      of the malleus and incus is observed in a number of human syndromes and results
      in conductive hearing loss. Understanding how this joint forms during normal
      development is thus an important step in furthering our understanding of such
      defects. RESULTS: We show that the developing incudomalleal joint is
      characterised by a lack of proliferation and discrete areas of apoptosis.
      Apoptosis has been suggested to aid in the removal of pre-cartilaginous cells
      from the joint region, allowing for the physical separation of the cartilaginous
      elements, however, we show that joint initiation is unaffected by blocking
      apoptosis. There is also no evidence of cell migration out of the presumptive
      joint region, as observed by labelling of joint and ossicle cells in culture.
      Using Type II collagen lacZ reporter mice, however, it is evident that cells in
      the presumptive joint region remain in place and downregulate cartilage markers.
      CONCLUSION: The malleus and incus first appear as a single united condensation
      expressing early cartilage markers. The incudomalleal joint region forms by cells
      in the presumptive joint region switching off cartilage markers and turning on
      joint markers. Failure in this process may result in fusion of this joint, as
      observed in human syndromes such as Branchio-Oto-Renal Syndrome or Treacher
      Collins Syndrome.

PMID- 18053236
TI  - Four-week short chain fructo-oligosaccharides ingestion leads to increasing fecal
      bifidobacteria and cholesterol excretion in healthy elderly volunteers.
AB  - BACKGROUND: Short-chain fructo-oligosaccharides (scFOS) are increasingly used in
      human diet for their prebiotic properties. We aimed at investigating the effects
      of scFOS ingestion on the colonic microflora and oro-fecal transit time in
      elderly healthy humans. METHODS: Stools composition, oro-fecal transit time, and
      clinical tolerance were evaluated in 12 healthy volunteers, aged 69 +/- 2 yrs, in
      three consecutive periods: basal period (2 weeks), scFOS (Actilight) ingestion
      period (8 g/d for 4 weeks) and follow-up period (4 weeks). Two-way ANOVA, with
      time and treatment as factors, was used to compare the main outcome measures
      between the three periods. RESULTS: Fecal bifidobacteria counts were
      significantly increased during the scFOS period (9.17 +/- 0.17 log cfu/g vs 8.52
      +/- 0.26 log cfu/g during the basal period) and returned to their initial values
      at the end of follow-up (8.37 +/- 0.21 log cfu/g; P < 0.05). Fecal cholesterol
      concentration increased during the scFOS period (8.18 +/- 2.37 mg/g dry matter vs
      2.81 +/- 0.94 mg/g dry matter during the basal period) and returned to the
      baseline value at the end of follow-up (2.87 +/- 0.44 mg/g dry matter; P < 0.05).
      Fecal pH tended to decrease during scFOS ingestion and follow-up periods compared
      to the basal period (P = 0.06). Fecal bile acids, stool weight, water percentage,
      and oro-fecal transit time did not change throughout the study. Excess flatus and
      bloating were significantly more frequent during scFOS ingestion when compared to
      the basal period (P < 0.05), but the intensity of these symptoms was very mild.
      CONCLUSION: Four-week 8 g/d scFOS ingestion is well tolerated and leads to a
      significant increase in fecal bifidobacteria in healthy elderly subjects. Whether
      the change in cholesterol metabolism found in our study could exert a beneficial
      action warrants further studies.

PMID- 18053237
TI  - Plasma concentrations of cortisol and PGF2alpha metabolite in Danish sows during
      mating, and intrauterine and conventional insemination.
AB  - BACKGROUND: The aims of the present work was to study whether there are any
      relationships between cortisol and PG-metabolite in mated sows or inseminated
      with the intrauterine technique and compare these to changes occurring in
      conventionally inseminated sow. METHODS: Thirty three crossbred sows (Danish
      Landrace x Danish Large White) were fitted with jugular vein catheters through
      vena auricularis from one of the ears. The sows were randomly divided into three
      groups (Boar-, IUI- and AI-group) and blood samples were collected before, during
      and after service. In a final evaluation only 25 sows that became pregnant and
      farrowed piglets at full term were used. RESULTS: Cortisol concentrations
      increased in all groups but Boar-group (n = 8) had a significantly higher
      cortisol during 10 to 20 min after service than sows in AI-group (n = 8). In
      mated sows cortisol concentrations peaked at 15 minutes after service. The Boar
      group (n = 8) showed no ascending PG-metabolite levels during the whole
      experiment, while both IUI- and AI-groups (n = 9 and n = 8, respectively) had a
      2.5-fold increase in PG-metabolite 15 minutes after service. CONCLUSION: In
      conclusion, mating of sows by a boar results in a greater increase of cortisol
      than AI and without an elevation of PG-metabolite levels, which was seen in both
      the inseminated groups. It was also demonstrated that IUI-group had an earlier
      significant increase of PG-metabolite levels than sows inseminated
      conventionally. Further investigation using different semen extenders or even
      different type of insemination catheters might be helpful in understanding the
      reason for an immediate increase of PG-metabolite after insemination but not
      after mating.

PMID- 18053238
TI  - Genome-wide interacting effects of sucrose and herbicide-mediated stress in
      Arabidopsis thaliana: novel insights into atrazine toxicity and sucrose-induced
      tolerance.
AB  - BACKGROUND: Soluble sugars, which play a central role in plant structure and
      metabolism, are also involved in the responses to a number of stresses, and act
      as metabolite signalling molecules that activate specific or hormone-crosstalk
      transduction pathways. The different roles of exogenous sucrose in the tolerance
      of Arabidopsis thaliana plantlets to the herbicide atrazine and oxidative stress
      were studied by a transcriptomic approach using CATMA arrays. RESULTS: Parallel
      situations of xenobiotic stress and sucrose-induced tolerance in the presence of
      atrazine, of sucrose, and of sucrose plus atrazine were compared. These
      approaches revealed that atrazine affected gene expression and therefore seedling
      physiology at a much larger scale than previously described, with potential
      impairment of protein translation and of reactive-oxygen-species (ROS) defence
      mechanisms. Correlatively, sucrose-induced protection against atrazine injury was
      associated with important modifications of gene expression related to ROS defence
      mechanisms and repair mechanisms. These protection-related changes of gene
      expression did not result only from the effects of sucrose itself, but from
      combined effects of sucrose and atrazine, thus strongly suggesting important
      interactions of sucrose and xenobiotic signalling or of sucrose and ROS
      signalling. CONCLUSION: These interactions resulted in characteristic
      differential expression of gene families such as ascorbate peroxidases,
      glutathione-S-transferases and cytochrome P450s, and in the early induction of an
      original set of transcription factors. These genes used as molecular markers will
      eventually be of great importance in the context of xenobiotic tolerance and
      phytoremediation.

PMID- 18053239
TI  - Hospital outpatient perceptions of the physical environment of waiting areas: the
      role of patient characteristics on atmospherics in one academic medical center.
AB  - BACKGROUND: This study examines hospital outpatient perceptions of the physical
      environment of the outpatient waiting areas in one medical center. The
      relationship of patient characteristics and their perceptions and needs for the
      outpatient waiting areas are also examined. METHOD: The examined medical center
      consists of five main buildings which house seventeen primary waiting areas for
      the outpatient clinics of nine medical specialties: 1) Internal Medicine; 2)
      Surgery; 3) Ophthalmology; 4) Obstetrics-Gynecology and Pediatrics; 5) Chinese
      Medicine; 6) Otolaryngology; 7) Orthopedics; 8) Family Medicine; and 9)
      Dermatology. A 15-item structured questionnaire was developed to rate patient
      satisfaction covering the four dimensions of the physical environments of the
      outpatient waiting areas: 1) visual environment; 2) hearing environment; 3) body
      contact environment; and 4) cleanliness. The survey was conducted between
      November 28, 2005 and December 8, 2005. A total of 680 outpatients responded.
      Descriptive, univariate, and multiple regression analyses were applied in this
      study. RESULTS: All of the 15 items were ranked as relatively high with a range
      from 3.362 to 4.010, with a neutral score of 3. Using a principal component
      analysis' summated scores of four constructed dimensions of patient satisfaction
      with the physical environments (i.e. visual environment, hearing environment,
      body contact environment, and cleanliness), multiple regression analyses revealed
      that patient satisfaction with the physical environment of outpatient waiting
      areas was associated with gender, age, visiting frequency, and visiting time.
      CONCLUSION: Patients' socio-demographics and context backgrounds demonstrated to
      have effects on their satisfaction with the physical environment of outpatient
      waiting areas. In addition to noticing the overall rankings for less satisfactory
      items, what should receive further attention is the consideration of the
      patients' personal characteristics when redesigning more comfortable and
      customized physical environments of waiting areas.

PMID- 18053240
TI  - Perception versus polysomnographic assessment of sleep in CFS and non-fatigued
      control subjects: results from a population-based study.
AB  - BACKGROUND: Complaints of unrefreshing sleep are a prominent component of chronic
      fatigue syndrome (CFS); yet, polysomnographic studies have not consistently
      documented sleep abnormalities in CFS patients. We conducted this study to
      determine whether alterations in objective sleep characteristics are associated
      with subjective measures of poor sleep quality in persons with CFS. METHODS: We
      examined the relationship between perceived sleep quality and polysomnographic
      measures of nighttime and daytime sleep in 35 people with CFS and 40 non-fatigued
      control subjects, identified from the general population of Wichita, Kansas and
      defined by empiric criteria. Perceived sleep quality and daytime sleepiness were
      assessed using clinical sleep questionnaires. Objective sleep characteristics
      were assessed by nocturnal polysomnography and daytime multiple sleep latency
      testing. RESULTS: Participants with CFS reported unrefreshing sleep and problems
      sleeping during the preceding month significantly more often than did non
      fatigued controls. Participants with CFS also rated their quality of sleep during
      the overnight sleep study as significantly worse than did control subjects.
      Control subjects reported significantly longer sleep onset latency than latency
      to fall asleep as measured by PSG and MSLT. There were no significant differences
      in sleep pathology or architecture between subjects with CFS and control
      subjects. CONCLUSION: People with CFS reported sleep problems significantly more
      often than control subjects. Yet, when measured these parameters and sleep
      architecture did not differ between the two subject groups. A unique finding
      requiring further study is that control, but not CFS subjects, significantly over
      reported sleep latency suggesting CFS subjects may have an increased appreciation
      of sleep behaviour that may contribute to their perception of sleep problems.

PMID- 18053241
TI  - A simple way to distinguish bed clothing contamination in a whole body bone scan:
      a case report.
AB  - Whole body bone scan with Technetium-99m MDP (methylene diphosphate) can detect
      bony lesions due to altered osteoblastic activity.Non-physiologic or increased
      radiotracer uptake in the bony structures of patients with a history of malignant
      diseases is usually interpreted as being suspicious of bone metastasis. It is
      extremely important to properly distinguish false positive sites of Tc-99m MDP
      localization. We present three patients with the same pattern of Tc-99m MDP
      abnormality in different locations. These scans were all performed on the same
      day to evaluate possible bone metastases in three patients with breast carcinoma.
      After careful examination, repeated images revealed bed clothing contamination.
      This is different from bed contamination by displacement among different
      patients. It is also different from detector contamination by limited area of
      involvement where detector contamination appears as a line throughout the total
      body projection. It can be helpful if a nuclear medicine specialist has a brief
      look at all scans prior to reporting them. In cases where the same pattern of
      abnormality is repeated in all images, the possibility of technical error such as
      bed clothing contamination rather than a pathological abnormality should be borne
      in mind.

PMID- 18053242
TI  - Mononuclear cells modulate the activity of pancreatic stellate cells which in
      turn promote fibrosis and inflammation in chronic pancreatitis.
AB  - BACKGROUND: Interactions between mononuclear cells and activated pancreatic
      myofibroblasts (pancreatic stellate cells; PSC) may contribute to inflammation
      and fibrosis in chronic pancreatitis (CP). METHODS: Markers of fibrosis and
      inflammation were concomitantly analysed by immunohistochemistry in chronic
      pancreatitis tissues. In vitro, PSC were stimulated with TNFalpha and LPS.
      Primary human blood mononuclear cells (PBMC) and PSC were cocultured, followed by
      analysis of cytokines and extracellular matrix (ECM) proteins. PBMC were derived
      from healthy donors and CP and septic shock patients. RESULTS: In areas of
      mononuclear cell infiltration in chronic pancreatitis tissues, there was
      decreased immunoreactivity for collagen1 and fibronectin, in contrast to areas
      with sparse mononuclear cells, although PSC were detectable in both areas. LPS
      and TNFalpha induced collagen1 and fibronectin levels as well as the matrix
      degradation enzyme MMP-1. Coculture experiments with PSC and PBMC revealed
      increased fibronectin secretion induced by PBMC. In addition, donor and CP PBMC
      significantly induced an increase in IL-6, MCP-1 and TGFbeta levels under
      coculture conditions. Determination of the source of cytokines and ECM proteins
      by mRNA expression analysis confirmed PSC as major contributors of ECM
      production. The increase in cytokine expression was PBMC- and also PSC-derived.
      CONCLUSION: Mononuclear cells modulate the activity of pancreatic stellate cells,
      which may in turn promote fibrosis and inflammation.

PMID- 18053243
TI  - Genetic variability of the P120' surface protein gene of Mycoplasma hominis
      isolates recovered from Tunisian patients with uro-genital and infertility
      disorders.
AB  - BACKGROUND: Among the surface antigens of Mycoplasma hominis, the P120' protein
      was previously shown to elicit a subtle antibody response and appears to be
      relatively conserved. To get better insight into the evolution of this protein,
      we analysed the genetic variability of its surface exposed region in 27 M.
      hominis isolates recovered from the genital tract of Tunisian patients with
      infertility disorders. METHODS: All specimens were processed for culture and PCR
      amplification of the N-terminal surface exposed region of p120' gene. PCR
      products were sequenced to evaluate the genetic variability, to test for adaptive
      selection, and to infer the phylogenetic relationship of the M. hominis isolates.
      RESULTS: Sequence analysis showed a total of 25 single nucleotide polymorphisms
      distributed through 23 polymorphic sites, yielding 13 haplotypes. All but one
      mutation were confined within three distinct regions. Analysis of the amino acid
      based phylogenetic tree showed a predominant group of 17 closely related isolates
      while the remaining appear to have significantly diverged. CONCLUSION: By
      analysing a larger sample of M. hominis recovered from patients with urogenital
      infections, we show here that the P120' protein undergoes substantial level of
      genetic variability at its surface exposed region.

PMID- 18053244
TI  - Direct maximum parsimony phylogeny reconstruction from genotype data.
AB  - BACKGROUND: Maximum parsimony phylogenetic tree reconstruction from genetic
      variation data is a fundamental problem in computational genetics with many
      practical applications in population genetics, whole genome analysis, and the
      search for genetic predictors of disease. Efficient methods are available for
      reconstruction of maximum parsimony trees from haplotype data, but such data are
      difficult to determine directly for autosomal DNA. Data more commonly is
      available in the form of genotypes, which consist of conflated combinations of
      pairs of haplotypes from homologous chromosomes. Currently, there are no general
      algorithms for the direct reconstruction of maximum parsimony phylogenies from
      genotype data. Hence phylogenetic applications for autosomal data must therefore
      rely on other methods for first computationally inferring haplotypes from
      genotypes. RESULTS: In this work, we develop the first practical method for
      computing maximum parsimony phylogenies directly from genotype data. We show that
      the standard practice of first inferring haplotypes from genotypes and then
      reconstructing a phylogeny on the haplotypes often substantially overestimates
      phylogeny size. As an immediate application, our method can be used to determine
      the minimum number of mutations required to explain a given set of observed
      genotypes. CONCLUSION: Phylogeny reconstruction directly from unphased data is
      computationally feasible for moderate-sized problem instances and can lead to
      substantially more accurate tree size inferences than the standard practice of
      treating phasing and phylogeny construction as two separate analysis stages. The
      difference between the approaches is particularly important for downstream
      applications that require a lower-bound on the number of mutations that the
      genetic region has undergone.

PMID- 18053246
TI  - Incidence of human herpesvirus 8 (HHV-8) infection among HIV-uninfected
      individuals at high risk for sexually transmitted infections.
AB  - BACKGROUND: The occurrence of, and risk factors for, HHV-8 infection have yet to
      be definitively determined, particularly among heterosexual individuals with at
      risk behavior for sexually transmitted infections (STI). The objective of this
      study was to estimate the incidence and determinants of HHV-8 infection among HIV
      uninfected individuals repeatedly attending an urban STI clinic. METHODS: Sera
      from consecutive HIV-uninfected individuals repeatedly tested for HIV-1
      antibodies were additionally tested for HHV-8 antibodies using an
      immunofluorescence assay. To identify determinants of HHV-8 infection, a nested
      case-control study and multivariate logistic regression analysis were performed.
      RESULTS: Sera from 456 HIV-uninfected individuals (224 multiple-partner
      heterosexuals and 232 men who have sex with men (MSM]) were identified for
      inclusion in the study. The HHV-8 seroprevalence at enrollment was 9.4% (21/224;
      95% C.I.: 6.0-14.2%) among heterosexuals with multiple partners and 22.0%
      (51/232; 95% C.I.: 16.9-28.0%) among MSM. Among the 203 multiple-partner
      heterosexuals and 181 MSM who were initially HHV-8-negative, 17 (IR = 3.0/100 p
      y, 95% C.I.: 1.9 - 4.8) and 21 (IR = 3.3/100 p-y, 95% C.I:.2.1 - 5.1)
      seroconversions occurred, respectively. HHV-8 seroconversion tended to be
      associated with a high number of sexual partners during the follow-up among MSM
      (> 10 partners: AOR = 3.32 95% CI:0.89-12.46) and among the multiple-partner
      heterosexuals (> 10 partner; AOR = 3.46, 95% CI:0.42-28.2). Moreover, among MSM,
      HHV-8 seroconversion tended to be associated with STI (AOR = 1.80 95%CI: 0.52
      7.96). During the study period the HIV-1 incidence was lower than that of HHV-8
      among both groups (0.89/100 p-y among MSM and 0.95/100 p-y among multiple-partner
      heterosexuals). CONCLUSION: The large difference between the incidence of HHV-8
      and the incidence of HIV-1 and other STIs may suggest that the circulation of HHV
      8 is sustained by practices other than classical at-risk sexual behavior.

PMID- 18053245
TI  - NMR and X-ray analysis of structural additivity in metal binding site-swapped
      hybrids of rubredoxin.
AB  - BACKGROUND: Chimeric hybrids derived from the rubredoxins of Pyrococcus furiosus
      (Pf) and Clostridium pasteurianum (Cp) provide a robust system for the
      characterization of protein conformational stability and dynamics in a
      differential mode. Interchange of the seven nonconserved residues of the metal
      binding site between the Pf and Cp rubredoxins yields a complementary pair of
      hybrids, for which the sum of the thermodynamic stabilities is equal to the sum
      for the parental proteins. Furthermore, the increase in amide hydrogen exchange
      rates for the hyperthermophile-derived metal binding site hybrid is faithfully
      mirrored by a corresponding decrease for the complementary hybrid that is derived
      from the less thermostable rubredoxin, indicating a degree of additivity in the
      conformational fluctuations that underlie these exchange reactions. RESULTS:
      Initial NMR studies indicated that the structures of the two complementary
      hybrids closely resemble "cut-and-paste" models derived from the parental Pf and
      Cp rubredoxins. This protein system offers a robust opportunity to characterize
      differences in solution structure, permitting the quantitative NMR chemical shift
      and NOE peak intensity data to be analyzed without recourse to the conventional
      conversion of experimental NOE peak intensities into distance restraints. The
      intensities for 1573 of the 1652 well-resolved NOE crosspeaks from the hybrid
      rubredoxins were statistically indistinguishable from the intensities of the
      corresponding parental crosspeaks, to within the baseplane noise level of these
      high sensitivity data sets. The differences in intensity for the remaining 79 NOE
      crosspeaks were directly ascribable to localized dynamical processes. Subsequent
      X-ray analysis of the metal binding site-swapped hybrids, to resolution limits of
      0.79 A and 1.04 A, demonstrated that the backbone and sidechain heavy atoms in
      the NMR-derived structures lie within the range of structural variability
      exhibited among the individual molecules in the crystallographic asymmetric unit
      (approximately 0.3 A), indicating consistency with the "cut-and-paste"
      structuring of the hybrid rubredoxins in both crystal and solution. CONCLUSION:
      Each of the significant energetic interactions in the metal binding site-swapped
      hybrids appears to exhibit a 1-to-1 correspondence with the interactions present
      in the corresponding parental rubredoxin structure, thus providing a structural
      basis for the observed additivity in conformational stability and dynamics. The
      congruence of these X-ray and NMR experimental data offers additional support for
      the interpretation that the conventional treatment of NOE distance restraints
      contributes substantially to the systematic differences that are commonly
      reported between NMR- and X-ray-derived protein structures.

PMID- 18053247
TI  - Medical theses as part of the scientific training in basic medical and dental
      education: experiences from Finland.
AB  - BACKGROUND: Teaching the principles of scientific research in a comprehensive way
      is important at medical and dental schools. In many countries medical and dental
      training is not complete until the candidate has presented a diploma thesis. The
      objective of this study was to evaluate the nature, quality, publication pattern
      and visibility of Finnish medical diploma theses. METHODS: A total of 256 diploma
      theses presented at the University of Oulu from 2001 to 2003 were analysed. Using
      a standardised questionnaire, we extracted several characteristics from each
      thesis. We used the name of the student to assess whether the thesis resulted in
      a scientific publication indexed in medical article databases. The number of
      citations received by each published thesis was also recorded. RESULTS: A high
      proportion of the theses (69.5%) were essentially statistical in character, often
      combined with an extensive literature review or the development of a laboratory
      method. Most of them were supervised by clinical departments (55.9%). Only 61
      theses (23.8%) had been published in indexed scientific journals. Theses in the
      fields of biomedicine and diagnostics were published in more widely cited
      journals. The median number of citations received per year was 2.7 and the range
      from 0 to 14.7. CONCLUSION: The theses were seldom written according to the
      principles of scientific communication and the proportion of actually published
      was small. The visibility of these theses and their dissemination to the
      scientific community should be improved.

PMID- 18053248
TI  - Spatial transcription of CYP1A in fish liver.
AB  - BACKGROUND: The aim of this work was to study how evenly detoxifying genes are
      transcribed spatially in liver tissue of fish. Ten Atlantic salmon Salmo salar
      were intraperitoneally injected with 50 mg/kg of the strong CYP1A inducer beta
      naphthoflavone and liver tissue harvested seven days later. The liver from 10
      control and 10 exposed fish were split into eight sections, RNA extracted and
      three reference (beta-actin, elongation factor 1AB (EF1AB)) and two detoxifying
      genes (CYP1A and GST) quantified with real-time RT-PCR. The cellular localization
      of the EF1AB and CYP1A mRNA in the liver of control and beta-naphthoflavone
      treated fish was then determined by in situ hybridization (ISH) using EF1AB and
      CYP1A biotinylated oligonucleotide probes. RESULTS: The study shows that genes
      encoding phase I and phase II conjugating enzymes are unevenly transcribed in
      different parts of the liver of Atlantic salmon seven days after a single-dose of
      beta-naphthoflavone exposure. Transcription of CYP1A and GST was higher in the
      middle section of the liver compared to the distal and proximal parts of the
      organ. The ISH data suggest that CYP1A transcription happens mainly in hepatocyte
      cells in the liver, and that hepatocytes in the vicinity of blood vessels respond
      stronger to beta-naphthoflavone than cells further away from the blood supply.
      CONCLUSION: Overall, the qRT-PCR and ISH results reported here suggest that gene
      expression analysis should be performed on as pure cell populations as possible.
      If bulk tissue samples are to be used, one should always check how evenly the
      target genes are expressed in tissue sections and organs in every study.

PMID- 18053249
TI  - Chondrocyte outgrowth into a gelatin scaffold in a single impact load model of
      damage/repair - effect of BMP-2.
AB  - BACKGROUND: Articular cartilage has little capacity for repair in vivo, however,
      a small number of studies have shown that, in vitro, a damage/repair response can
      be induced. Recent work by our group has shown that cartilage can respond to
      single impact load and culture by producing repair cells on the articular
      surface. The purpose of this study was to identify whether chondrocyte outgrowth
      into a 3D scaffold could be observed following single impact load and culture.
      The effect of bone morphogenic-2 (BMP-2) on this process was investigated.
      METHODS: Cartilage explants were single impact loaded, placed within a scaffold
      and cultured for up to 20 days +/- BMP-2. Cell numbers in the scaffold, on and
      extruding from the articular surface were quantified and the immunohistochemistry
      used to identify the cellular phenotype. RESULTS: Following single impact load
      and culture, chondrocytes were observed in a 3D gelatin scaffold under all
      culture conditions. Chondrocytes were also observed on the articular surface of
      the cartilage and extruding out of the parent cartilage and on to the cartilage
      surface. BMP-2 was demonstrated to quantitatively inhibit these events.
      CONCLUSION: These studies demonstrate that articular chondrocytes can be
      stimulated to migrate out of parent cartilage following single impact load and
      culture. The addition of BMP-2 to the culture medium quantitatively reduced the
      repair response. It may be that the inhibitory effect of BMP-2 in this
      experimental model provides a clue to the apparent inability of articular
      cartilage to heal itself following damage in vivo.

PMID- 18053250
TI  - Broad network-based predictability of Saccharomyces cerevisiae gene loss-of
      function phenotypes.
AB  - We demonstrate that loss-of-function yeast phenotypes are predictable by guilt-by
      association in functional gene networks. Testing 1,102 loss-of-function
      phenotypes from genome-wide assays of yeast reveals predictability of diverse
      phenotypes, spanning cellular morphology, growth, metabolism, and quantitative
      cell shape features. We apply the method to extend a genome-wide screen by
      predicting, then verifying, genes whose disruption elongates yeast cells, and to
      predict human disease genes. To facilitate network-guided screens, a web server
      is available http://www.yeastnet.org.

PMID- 18053251
TI  - Differential inhibition of human cytomegalovirus (HCMV) by toll-like receptor
      ligands mediated by interferon-beta in human foreskin fibroblasts and cervical
      tissue.
AB  - Human cytomegalovirus (HCMV) can be acquired sexually and is shed from the
      genital tract. Cross-sectional studies in women show that changes in genital
      tract microbial flora affect HCMV infection and/or shedding. Since genital
      microbial flora may affect HCMV infection or replication by stimulating cells
      through Toll-like receptors (TLR), we assessed the effects of defined TLR-ligands
      on HCMV replication in foreskin fibroblasts and ectocervical tissue. Poly I:C (a
      TLR3-ligand) and lipopolysaccharide (LPS, a TLR4-ligand) inhibited HCMV and
      induced secretion of IL-8 and Interferon-beta (IFNbeta) in both foreskin
      fibroblasts and ectocervical tissue. The anti-HCMV effect was reversed by
      antibody to IFNbeta. CpG (TLR9 ligand) and lipoteichoic acid (LTA, TLR2 ligand)
      also inhibited HCMV infection in ectocervical tissue and this anti-HCMV effect
      was also reversed by anti-IFNbeta antibody. In contrast, LTA and CpG did not
      inhibit HCMV infection in foreskin fibroblasts. This study shows that TLR ligands
      induce an HCMV-antiviral effect that is mediated by IFNbeta suggesting that
      changes in genital tract flora may affect HCMV infection or shedding by
      stimulating TLR. This study also contrasts the utility of two models that can be
      used for assessing the interaction of microbial flora with HCMV in the genital
      tract. Clear differences in the response to different TLR ligands suggests the
      explant model more closely reflects in vivo responses to genital infections.

PMID- 18053253
TI  - Conceptualizing childhood health problems using survey data: a comparison of key
      indicators.
AB  - BACKGROUND: Many definitions are being used to conceptualize child health
      problems. With survey data, commonly used indicators for identifying children
      with health problems have included chronic condition checklists, measures of
      activity limitations, elevated service use, and health utility thresholds. This
      study compares these different indicators in terms of the prevalence rates
      elicited, and in terms of how the subgroups identified differ. METHODS: Secondary
      data analyses used data from the National Longitudinal Survey of Children and
      Youth, which surveyed a nationally representative sample of Canadian children (n
      = 13,790). Descriptive analyses compared healthy children to those with health
      problems, as classified by any of the key indicators. Additional analyses
      examined differences between subgroups of children captured by a single indicator
      and those described as having health problems by multiple indicators. RESULTS:
      This study demonstrates that children captured by any of the indicators had
      poorer health than healthy children, despite the fact that over half the sample
      (52.2%) was characterized as having a health problem by at least one indicator.
      Rates of child ill health differed by indicator; 5.6% had an activity limitation,
      9.2% exhibited a severe health difficulty, 31.7% reported a chronic condition,
      and 36.6% had elevated service use. Further, the four key indicators captured
      different types of children. Indicator groupings differed on child and socio
      demographic factors. Compared to children identified by more than one indicator,
      those identified only by the severe health difficulty indicator displayed more
      cognitive problems (p < 0.0001), those identified only by the chronic condition
      checklist had a greater likelihood of reporting allergies or asthma (p < 0.0001),
      and those identified as having elevated service use only were more affluent (p =
      0.01) and showed better overall health (p < 0.0001). Children identified by only
      a single indicator were less likely to have serious health problems than those
      identified by two or more indicators. CONCLUSION: We provide information useful
      to researchers when selecting indicators from survey data to identify children
      with health problems. Researchers and policy makers need to be aware of the
      impact of such definitions on prevalence rates as well as on the composition of
      children classified as being in poor health.

PMID- 18053252
TI  - Higher polymerase activity of a human influenza virus enhances activation of the
      hemagglutinin-induced Raf/MEK/ERK signal cascade.
AB  - Influenza viruses replicate within the nucleus of infected cells. Viral genomic
      RNA, three polymerase subunits (PB2, PB1, and PA), and the nucleoprotein (NP)
      form ribonucleoprotein complexes (RNPs) that are exported from the nucleus late
      during the infectious cycle. The virus-induced Raf/MEK/ERK (MAPK) signal cascade
      is crucial for efficient virus replication. Blockade of this pathway retards RNP
      export and reduces virus titers. Hemagglutinin (HA) accumulation and its tight
      association with lipid rafts activate ERK and enhance localization of cytoplasmic
      RNPs. We studied the induction of MAPK signal cascade by two seasonal human
      influenza A viruses A/HK/218449/06 (H3N2) and A/HK/218847/06 (H1N1) that differed
      substantially in their replication efficiency in tissue culture. Infection with
      H3N2 virus, which replicates efficiently, resulted in higher HA expression and
      its accumulation on the cell membrane, leading to substantially increased
      activation of MAPK signaling compared to that caused by H1N1 subtype. More H3N2
      HAs were expressed and accumulated on the cell membrane than did H1N1-HAs. Viral
      polymerase genes, particularly H3N2-PB1 and H3N2-PB2, were observed to contribute
      to increased viral polymerase activity. Applying plasmid-based reverse genetics
      to analyze the role of PB1 protein in activating HA-induced MAPK cascade showed
      that recombinant H1N1 virus possessing the H3N2-PB1 (rgH1N1/H3N2-PB1) induced
      greater ERK activation, resulting in increased nuclear export of the viral genome
      and higr virus titers. We conclude that enhanced viral polymerase activity
      promotes the replication and transcription of viral RNA leading to increased
      accumulation of HA on the cell surface and thereby resulting in an upregulation
      of the MAPK cascade and more efficient nuclear RNP-export as well as virus
      production.

PMID- 18053254
TI  - Arginine-to-lysine substitutions influence recombinant horseradish peroxidase
      stability and immobilisation effectiveness.
AB  - BACKGROUND: Horseradish Peroxidase (HRP) plays important roles in many
      biotechnological fields, including diagnostics, biosensors and biocatalysis.
      Often, it is used in immobilised form. With conventional immobilisation
      techniques, the enzyme adheres in random orientation: the active site may face
      the solid phase rather than bulk medium, impeding substrate access and leading to
      sub-optimal catalytic performance. The ability to immobilise HRP in a directional
      manner, such that the active site would always face outwards from the insoluble
      matrix, would maximise the immobilised enzyme's catalytic potential and could
      increase HRP's range of actual and potential applications. RESULTS: We have
      replaced arginine residues on the face of glycan-free recombinant HRP opposite to
      the active site by lysines. Our strategy differs from previous reports of
      specific HRP immobilisation via an engineered affinity tag or single reactive
      residue. These conservative Arg-to-Lys substitutions provide a means of
      multipoint covalent immobilisation such that the active site will always face
      away from the immobilisation matrix. One triple and one pentuple mutant were
      generated by substitution of solvent-exposed arginines on the "back" of the
      polypeptide (R118, R159 and R283) and of residues known to influence stability
      (K232 and K241). Orientated HRP immobilisation was demonstrated using a modified
      polyethersulfone (PES) membrane; the protein was forced to orientate its active
      site away from the membrane and towards the bulk solution phase. Mutant
      properties and bioinformatic analysis suggested the reversion of K283R to improve
      stability, thus generating two additional mutants (K118/R159K and
      R118K/K232N/K241F/R283K). While most mutants were less stable in free solution
      than wild type rHRP, the quadruple revertant regained some stability over its
      mutant counterparts. A greater degree of immobilisation on CNBr-activated
      Sepharosetrade mark was noted with increased lysine content; however, only
      marginal gains in solvent stability resulted from immobilisation on this latter
      matrix. CONCLUSION: Directional, orientated, immobilisation of rHRP mutants onto
      an activated, modified polyethersulfone membrane has been achieved with excellent
      retention of catalytic activity; however, re-engineering of acceptable stability
      characteristics into the "immobilisation mutants" will determine their
      applicability in diagnosis and biosensor development.

PMID- 18053255
TI  - Hospital admission patterns subsequent to diagnosis of type 1 diabetes in
      children : a systematic review.
AB  - BACKGROUND: Patients with type 1 diabetes are known to have a higher hospital
      admission rate than the underlying population and may also be admitted for
      procedures that would normally be carried out on a day surgery basis for non
      diabetics. Emergency admission rates have sometimes been used as indicators of
      quality of diabetes care. In preparation for a study of hospital admissions, a
      systematic review was carried out on hospital admissions for children diagnosed
      with type 1 diabetes, whilst under the age of 15. The main thrust of this review
      was to ascertain where there were gaps in the literature for studies
      investigating post-diagnosis hospitalisations, rather than to try to draw
      conclusions from the disparate data sets. METHODS: A systematic search of the
      electronic databases PubMed, Cochrane LibrarMEDLINE and EMBASE was conducted for
      the period 1986 to 2006, to identify publications relating to hospital admissions
      subsequent to the diagnosis of type 1 diabetes under the age of 15. RESULTS:
      Thirty-two publications met all inclusion criteria, 16 in Northern America, 11 in
      Europe and 5 in Australasia. Most of the studies selected were focussed on
      diabetic ketoacidosis (DKA) or diabetes-related hospital admissions and only four
      studies included data on all admissions. Admission rates with DKA as primary
      diagnosis varied widely between 0.01 to 0.18 per patient-year as did those for
      other diabetes-related co-morbidity ranging from 0.05 to 0.38 per patient year,
      making it difficult to interpret data from different study designs. However,
      people with Type 1 diabetes are three times more likely to be hospitalised than
      the non-diabetic populations and stay in hospital twice as long. CONCLUSION: Few
      studies report on all admissions to hospital in patients diagnosed with type 1
      diabetes whilst under the age of 15 years. Health care costs for type 1 patients
      are higher than those for the general population and information on associated
      patterns of hospitalisation might help to target interventions to reduce the cost
      of hospital admissions.

PMID- 18053256
TI  - Initial in vitro screening approach to investigate the potential health and
      environmental hazards of Enviroxtrade mark - a nanoparticulate cerium oxide
      diesel fuel additive.
AB  - Nanotechnology is the new industrial revolution of the 21st Century as the
      various processes lead to radical improvements in medicine, manufacturing, energy
      production, land remediation, information technology and many other everyday
      products and applications. With this revolution however, there are undoubted
      concerns for health, safety and the environment which arise from the unique
      nature of materials and processes at the nanometre scale.The in vitro assays used
      in the screening strategy are all validated, internationally accepted protocols
      and provide a useful indication of potential toxicity of a chemical as a result
      of effects on various toxicological endpoints such as local site of contact
      (dermal) irritation, general cytotoxicity and mutagenicity.The initial in vitro
      screening strategy described in this paper to investigate the potential health
      implications, if any, which may arise following exposure to one specific
      application of nanoparticulate cerium oxide used as a diesel fuel borne catalyst,
      reflects a precautionary approach and the results will inform judgement on how
      best to proceed to ensure safe use.

PMID- 18053257
TI  - The role of anxiety symptoms in school performance in a community sample of
      children and adolescents.
AB  - BACKGROUND: Anxiety symptoms are relatively common among children and adolescents
      and can interfere with functioning. The prevalence of anxiety and the
      relationship between anxiety and school performance were examined among
      elementary, middle, and high school students. METHODS: Samples of elementary (N =
      131, age 8-10 years), middle (N = 267, age 11-13 years), and high school (N = 80,
      age 14-16 years) children were recruited from four public schools in a
      predominantly middle-class community in Catania, Italy. Children completed the
      Multidimensional Anxiety Scale for Children (MASC). T-scores were computed for
      the MASC total scores, and considered to be in the anxious range if 65 or above.
      Current academic grades were obtained from school records. RESULTS: Of the 478
      children, 35 (7.3%) had a MASC T-score in the anxious range. The rate of children
      in the anxious range was 2.3% in elementary, 7.9% in middle, and 15.9% in high
      school (chi2 = 7.8, df = 2, p < 0.05), and was 14.1% among students with
      insufficient grades, 9.4% among those with sufficient grades, and 3.9% among
      those with good or very good grades (chi2 = 11.68, df = 2, p < 0.01). CONCLUSION:
      In this community sample of children and adolescents attending elementary through
      high school, the prevalence of abnormally high self-reported levels of anxiety
      increased in frequency with age and was negatively associated with school
      performance.

PMID- 18053259
TI  - Immigrant families' perceptions on walking to school and school breakfast: a
      focus group study.
AB  - BACKGROUND: Immigrant children face an increased risk of being overweight. Little
      is known about how immigrant families perceive school programs that may help
      prevent obesity, such as walking to school and school breakfast. METHODS: Six
      focus groups (n = 53) were conducted with immigrant parents of school-aged
      children, two each in three languages: Vietnamese, Spanish, and Somali. A
      facilitator and translator conducted the focus groups using a script and question
      guide. Written notes and audio transcripts were recorded in each group.
      Transcripts were coded for themes by two researchers and findings classified
      according to an ecological model. RESULTS: Participants in each ethnic group held
      positive beliefs about the benefits of walking and eating breakfast. Barriers to
      walking to school included fear of children's safety due to stranger abductions,
      distrust of neighbors, and traffic, and feasibility barriers due to distance to
      schools, parent work constraints, and large families with multiple children.
      Barriers to school breakfast participation included concerns children would not
      eat due to lack of appealing/appropriate foods and missing breakfast due to late
      bus arrival or lack of reminders. Although some parents acknowledged concerns
      about child and adult obesity overall, obesity concerns did not seem personally
      relevant. CONCLUSION: Immigrant parents supported the ideals of walking to school
      and eating breakfast, but identified barriers to participation in school programs
      across domains of the ecological model, including community, institution, and
      built environment factors. Schools and communities serving immigrant families may
      need to address these barriers in order to engage parents and children in walking
      and breakfast programs.

PMID- 18053258
TI  - The Lothian Birth Cohort 1936: a study to examine influences on cognitive ageing
      from age 11 to age 70 and beyond.
AB  - BACKGROUND: Cognitive ageing is a major burden for society and a major influence
      in lowering people's independence and quality of life. It is the most feared
      aspect of ageing. There are large individual differences in age-related cognitive
      changes. Seeking the determinants of cognitive ageing is a research priority. A
      limitation of many studies is the lack of a sufficiently long period between
      cognitive assessments to examine determinants. Here, the aim is to examine
      influences on cognitive ageing between childhood and old age. METHODS/DESIGN: The
      study is designed as a follow-up cohort study. The participants comprise
      surviving members of the Scottish Mental Survey of 1947 (SMS1947; N = 70,805) who
      reside in the Edinburgh area (Lothian) of Scotland. The SMS1947 applied a valid
      test of general intelligence to all children born in 1936 and attending Scottish
      schools in June 1947. A total of 1091 participants make up the Lothian Birth
      Cohort 1936. They undertook: a medical interview and examination; physical
      fitness testing; extensive cognitive testing (reasoning, memory, speed of
      information processing, and executive function); personality, quality of life and
      other psycho-social questionnaires; and a food frequency questionnaire. They have
      taken the same mental ability test (the Moray House Test No. 12) at age 11 and
      age 70. They provided blood samples for DNA extraction and testing and other
      biomarker analyses. Here we describe the background and aims of the study, the
      recruitment procedures and details of numbers tested, and the details of all
      examinations. DISCUSSION: The principal strength of this cohort is the rarely
      captured phenotype of lifetime cognitive change. There is additional rich
      information to examine the determinants of individual differences in this
      lifetime cognitive change. This protocol report is important in alerting other
      researchers to the data available in the cohort.

PMID- 18053260
TI  - A quantitative synthesis of the medicinal ethnobotany of the Malinke of Mali and
      the Ashaninka of Peru, with a new theoretical framework.
AB  - BACKGROUND: Although ethnomedically and taxonomically guided searches for new
      medicinal plants can improve the percentage of plants found containing active
      compounds when compared to random sampling, ethnobotany has fulfilled little of
      its promise in the last few decades to deliver a bounty of new, laboratory-proven
      medicinal plants and compounds. It is quite difficult to test, isolate, and
      elucidate the structure and mechanism of compounds from the plethora of new
      medicinal plant uses described each year with limited laboratory time and
      resources and the high cost of clinical trials of new drug candidates. METHODS: A
      new quantitative theoretical framework of mathematical formulas called
      "relational efficacy" is proposed that should narrow down this search for new
      plant-derived medicines based on the hypothesis that closely related plants used
      to treat closely related diseases in distantly related cultures have a higher
      probability of being effective because they are more likely to be independent
      discoveries of similar plant compounds and disease mechanisms. A prerequisite to
      this hypothesis, the idea that empirical testing in traditional medicine will
      lead to choosing similar medicinal plants and therefore the medicinal flora of
      two distant cultures will prove to be more similar than their general flora, is
      tested using resampling statistics on cross-cultural field data of the plants
      used by the Malinke of Mali and the Ashaninka of Peru to treat the diseases
      malaria, African sleeping sickness, Chagas' disease, leishmaniasis, diabetes,
      eczema, asthma, and uterine fibroids. RESULTS: In this case, the similarity of
      the medicinal floras is found to be significantly greater than the similarity of
      the general floras, but only when the diseases in question are grouped into the
      categories of parasitic and autoimmune diseases. CONCLUSION: If the central
      theoretical framework of this hypothesis is shown to be true, it will allow the
      synthesis of medicinal plant information from around the world to pinpoint the
      species with the highest potential efficacy to take into the laboratory and
      analyze further, ultimately saving much field and laboratory time and resources.

PMID- 18053261
TI  - Continuous exposure to Plasmodium results in decreased susceptibility and
      transcriptomic divergence of the Anopheles gambiae immune system.
AB  - BACKGROUND: Plasmodium infection has been shown to compromise the fitness of the
      mosquito vector, reducing its fecundity and longevity. However, from an
      evolutionary perspective, the impact of Plasmodium infection as a selective
      pressure on the mosquito is largely unknown. RESULTS: In the present study we
      have addressed the effect of a continuous Plasmodium berghei infection on the
      resistance to infection and global gene expression in Anopheles gambiae. Exposure
      of A. gambiae to P. berghei-infected blood and infection for 16 generations
      resulted in a decreased susceptibility to infection, altered constitutive
      expression levels for approximately 2.4% of the mosquito's total transcriptome
      and a lower basal level of immune genes expression, including several anti
      Plasmodium factors. The infection-responsiveness for several defense genes was
      elevated in the P. berghei exposed mosquito colonies. CONCLUSION: Our study
      establishes the existence of a selective pressure exerted by the parasite P.
      berghei on the malaria vector A. gambiae that results in a decreased
      permissiveness to infection and changes in the mosquito transcriptome regulation
      that suggest a decreased constitutive immune gene activity but a more potent
      immune response upon Plasmodium challenge.

PMID- 18053262
TI  - Biologically induced mineralization of dypingite by cyanobacteria from an
      alkaline wetland near Atlin, British Columbia, Canada.
AB  - BACKGROUND: This study provides experimental evidence for biologically induced
      precipitation of magnesium carbonates, specifically dypingite
      (Mg5(CO3)4(OH)2.5H2O), by cyanobacteria from an alkaline wetland near Atlin,
      British Columbia. This wetland is part of a larger hydromagnesite
      (Mg5(CO3)4(OH)2.4H2O) playa. Abiotic and biotic processes for magnesium carbonate
      precipitation in this environment are compared. RESULTS: Field observations show
      that evaporation of wetland water produces carbonate films of nesquehonite
      (MgCO3.3H2O) on the water surface and crusts on exposed surfaces. In contrast,
      benthic microbial mats possessing filamentous cyanobacteria (Lyngbya sp.) contain
      platy dypingite (Mg5(CO3)4(OH)2.5H2O) and aragonite. Bulk carbonates in the
      benthic mats (delta13C avg. = 6.7%, delta 18O avg. = 17.2%) were isotopically
      distinguishable from abiotically formed nesquehonite (delta13C avg. = 9.3%, delta
      18O avg. = 24.9%). Field and laboratory experiments, which emulated natural
      conditions, were conducted to provide insight into the processes for magnesium
      carbonate precipitation in this environment. Field microcosm experiments included
      an abiotic control and two microbial systems, one containing ambient wetland
      water and one amended with nutrients to simulate eutrophic conditions. The
      abiotic control developed an extensive crust of nesquehonite on its bottom
      surface during which [Mg2+] decreased by 16.7% relative to the starting
      concentration. In the microbial systems, precipitation occurred within the mats
      and was not simply due to the capturing of mineral grains settling out of the
      water column. Magnesium concentrations decreased by 22.2% and 38.7% in the
      microbial systems, respectively. Laboratory experiments using natural waters from
      the Atlin site produced rosettes and flakey globular aggregates of dypingite
      precipitated in association with filamentous cyanobacteria dominated biofilms
      cultured from the site, whereas the abiotic control again precipitated
      nesquehonite. CONCLUSION: Microbial mats in the Atlin wetland create ideal
      conditions for biologically induced precipitation of dypingite and have
      presumably played a significant role in the development of this natural Mg
      carbonate playa. This biogeochemical process represents an important link between
      the biosphere and the inorganic carbon pool.

PMID- 18053263
TI  - Onset of the Thermic Effect of Feeding (TEF): a randomized cross-over trial.
AB  - BACKGROUND: The purpose of this investigation was to identify the onset of the
      thermic effect of feeding (TEF) after ingestion of a high carbohydrate (CHO) and
      a high protein (PRO) 1255 kJ (300 kcal) drink. METHODS: Resting metabolic rate
      (RMR) and TEF were measured over 30-minute periods via indirect calorimetry using
      a ventilated hood technique. Eighteen subjects (7 men and 11 women) completed two
      randomized, double-blind trials. Data were collected in 1-minute measurement
      intervals. RMR was subtracted from TEF and the time of onset was obtained when
      two consecutive data points exceeded 5% and 10% of resting metabolic rate.
      RESULTS: At 5% above RMR the onset of TEF for CHO was 8.4 +/- 6.2 minutes and was
      not different as compared to PRO, 8.6 +/- 5.2 minutes (p = 0.77). Likewise, no
      differences were found with a 10% increase above RMR: CHO, 14.1 +/- 7.5 min; PRO,
      16.7 +/- 6.7 min (p = 0.36). Several subjects did not show a 10% increase within
      30-min. CONCLUSION: We conclude that the onset of TEF is variable among subjects
      but is initiated within about 5 to 20-min for most subjects after ingestion of a
      1255 kJ liquid meal. No differences were found between CHO or PRO liquid meals.

PMID- 18053264
TI  - Cerebral palsy in a total population of 4-11 year olds in southern Sweden.
      Prevalence and distribution according to different CP classification systems.
AB  - BACKGROUND: The aim of this study was to investigate the prevalence of cerebral
      palsy (CP) as well as to characterize the CP population, its participation in a
      secondary prevention programme (CPUP) and to validate the CPUP database. METHODS:
      The study population was born 1990-1997 and resident in Skane/Blekinge on Jan 1st
      2002. Multiple sources were used. Irrespective of earlier diagnoses,
      neuropaediatrician and other professional medical records were evaluated for all
      children at the child habilitation units. The CPUP database and diagnosis
      registers at hospital departments were searched for children with CP or
      psychomotor retardation, whose records were then evaluated. To enhance early
      prevention, CP/probable CP was searched for also in children below four years of
      age born 1998-2001. RESULTS: The prevalence of CP was 2.4/1,000 (95% CI 2.1-2.6)
      in children 4-11 years of age born in Sweden, excluding post-neonatally acquired
      CP. Children born abroad had a higher prevalence of CP with more severe
      functional limitations. In the total population, the prevalence of CP was
      2.7/1,000 (95% CI 2.4-3.0) and 48% were GMFCS-level I (the mildest limitation of
      gross motor function). One third of the children with CP, who were born or had
      moved into the area after a previous study in 1998, were not in the CPUP
      database. The subtype classification in the CPUP database was adjusted in the
      case of every fifth child aged 4-7 years not previously reviewed. CONCLUSION: The
      prevalence of CP and the subtype distribution did not differ from that reported
      in other studies, although the proportion of mild CP tended to be higher. The
      availability of a second opinion about the classification of CP/CP subtypes is
      necessary in order to keep a CP register valid, as well as an active search for
      undiagnosed CP among children with other impairments.

PMID- 18053265
TI  - Expression and function of nr4a2, lmx1b, and pitx3 in zebrafish dopaminergic and
      noradrenergic neuronal development.
AB  - BACKGROUND: Dopaminergic neurons form in diverse areas of the vertebrate di- and
      mesencephalon to constitute several major neuromodulatory systems. While much is
      known about mammalian mesencephalic dopaminergic neuron development, little is
      known about the specification of the diencephalic dopaminergic groups. The
      transcription factors Pitx3 and Lmx1b play an important role in mammalian
      mesencephalic dopaminergic specification, and Nurr1/Nr4a2 has been shown to
      contribute to specification of the dopaminergic neurotransmitter phenotype. We
      use zebrafish to analyze potentially evolutionarily conserved roles of these
      transcription factors in a vertebrate brain that lacks a mesencephalic
      dopaminergic system, but has an ascending dopaminergic system in the ventral
      diencephalon. RESULTS: We use a combination of fluorescent in situ hybridization
      and immunohistochemistry to determine whether nr4a2, lmx1b, and pitx3 genes are
      expressed in mature dopaminergic neurons or in potential precursor populations.
      We identify a second nr4a2 paralogue, nr4a2a, and find it co-expressed with
      Tyrosine hydroxylase in preoptic, pretectal and retinal amacrine dopaminergic
      neurons, while nr4a2b is only expressed in preoptic and retinal dopaminergic
      neurons. Both zebrafish nr4a2 paralogues are not expressed in ventral
      diencephalic dopaminergic neurons with ascending projections. Combined morpholino
      antisense oligo mediated knock-down of both nr4a2a and nr4a2b transcripts reveals
      that all zebrafish dopaminergic neurons expressing nr4a2a depend on Nr4a2
      activity for tyrosine hydroxylase and dopamine transporter expression. Zebrafish
      lmx1b.1 is expressed in noradrenergic neurons of the locus coeruleus and medulla
      oblongata, but knock-down reveals that it is specifically required for tyrosine
      hydroxylase expression only in the medulla oblongata area postrema noradrenergic
      neurons. Both lmx1b genes and pitx3 are not expressed in dopaminergic neurons,
      but in a diencephalic territory that might contain precursor cells for ventral
      diencephalic dopaminergic neurons. Upon morpholino knock-down of both lmx1b
      paralogues, the number of neurons in diencephalic dopaminergic clusters with
      ascending projections appears specifically reduced. Thus lmx1b paralogues may
      contribute to the generation of diencephalic dopaminergic precursors. Conversely,
      knock-down of pitx3 does not specifically affect any diencephalic DA cluster.
      CONCLUSION: Our data indicate a conserved evolutionary role of Nr4a2 proteins in
      specification of the neurotransmitter phenotype, albeit it appears to be only one
      of several regulatory modules of dopaminergic differentiation, as most ventral
      diencephalic dopaminergic neurons do not express nr4a2 genes in zebrafish. For
      zebrafish lmx1b genes, which are not expressed in mature dopaminergic neurons,
      our data suggest a role in diencephalic precursor populations contributing to the
      ascending dopaminergic systems. A di-mesencephalic longitudinal domain of lmx1b
      expression may be the basis for the expansion and posterior shift of ventral di
      /mesencephalic dopaminergic populations with ascending projections during
      evolution.

PMID- 18053266
TI  - My first time: initiation into injecting drug use in Manipur and Nagaland, north
      east India.
AB  - BACKGROUND: The north-east Indian states of Manipur and Nagaland are two of the
      six high HIV prevalence states in the country, and the main route of HIV
      transmission is injecting drug use. Understanding the pathways to injecting drug
      use can facilitate early intervention with HIV prevention programs. While several
      studies of initiation into injecting drug use have been conducted in developed
      countries, little is known about the situation in developing country settings.
      The aim of this study was to increase understanding of the contextual factors
      associated with initiation into injecting drug use in north-east India, and the
      influence of these factors on subsequent initiation of others. METHOD: In mid
      2006 a cross-sectional survey among 200 injecting drug users (IDUs) was
      undertaken in partnership with local NGOs that provide HIV prevention and care
      services and advocacy for IDUs in Imphal, Manipur and Dimapur, Nagaland. The
      questionnaire elicited detailed information about the circumstances of the first
      injection and the contexts of participants' lives. Demographic information, self
      reported HIV status, and details about initiation of others were also recorded.
      RESULTS: Initiation into injecting drug use occurred at 20 years of age. The
      drugs most commonly injected were Spasmo-proxyvon (65.5%) and heroin (30.5%). In
      53.5% cases, a needle belonging to someone else was used. Two-thirds (66.7%) had
      used the drug previously, and 91.0% had known other IDUs prior to initiation
      (mean = 7.5 others). The first injection was usually administered by another
      person (94.5%), mostly a friend (84.1%). Initiation is a social event; 98% had
      others present (mean = 2.7 others). Almost 70% of participants had initiated at
      least one other (mean = 5 others). Initiation of others was independently
      associated with being male and unemployed; having IDU friends and using alcohol
      around the time of initiation; and having been taught to inject and not paid for
      the drug at the time of initiation. CONCLUSION: Targeting harm reduction messages
      to (non-injecting) drug users and capitalising on existing IDU social networks to
      promote safe injecting and deter initiation of others are possible strategies for
      reducing the impact of injecting drug use and the HIV epidemic in north-east
      India.

PMID- 18053267
TI  - The management of an endodontically abscessed tooth: patient health state
      utility, decision-tree and economic analysis.
AB  - BACKGROUND: A frequent encounter in clinical practice is the middle-aged adult
      patient complaining of a toothache caused by the spread of a carious infection
      into the tooth's endodontic complex. Decisions about the range of treatment
      options (conventional crown with a post and core technique (CC), a single tooth
      implant (STI), a conventional dental bridge (CDB), and a partial removable
      denture (RPD)) have to balance the prognosis, utility and cost. Little is know
      about the utility patients attach to the different treatment options for an
      endontically abscessed mandibular molar and maxillary incisor. We measured
      patients' dental-health-state utilities and ranking preferences of the treatment
      options for these dental problems. METHODS: Forty school teachers ranked their
      preferences for conventional crown with a post and core technique, a single tooth
      implant, a conventional dental bridge, and a partial removable denture using a
      standard gamble and willingness to pay. Data previously reported on treatment
      prognosis and direct "out-of-pocket" costs were used in a decision-tree and
      economic analysis RESULTS: The Standard Gamble utilities for the restoration of a
      mandibular 1st molar with either the conventional crown (CC), single-tooth
      implant (STI), conventional dental bridge (CDB) or removable-partial-denture
      (RPD) were 74.47 [+/- 6.91], 78.60 [+/- 5.19], 76.22 [+/- 5.78], 64.80 [+/- 8.1]
      respectively (p < 0.05). Their respective Willingness-to-Pay ($CDN) were 1,782.05
      [+/- 361.42], 1,871.79 [+/- 349.44], 1,605.13 [+/- 348.10], 1,351.28 [+/- 368.62]
      (p < 0.05).The standard gamble utilities for the restoration of a maxillary
      central incisor with a CC, STI, CDB and RPD were 88.50 [+/- 6.12], 90.68 [+/-
      3.41], 89.78 [+/- 3.81] and 91.10 [+/- 3.57] respectively (p > 0.05). Their
      respective willingness-to-pay ($CDN) were: 1,782.05 [+/- 361.42], 1,871.79 [+/-
      349.44], 1,605.13 [+/- 348.10] and 1,351.28 [+/- 368.62]. A statistical
      difference was found between the utility of treating a maxillary central incisor
      and mandibular 1st-molar (p < 0.05).The expected-utility-value for a 5-year
      prosthetic survival was highest for the CDB and the STI treatment of an abscessed
      mandibular molar (74.75 and 71.47 respectively) and maxillary incisor (86.24 and
      84.91 respectively). This held up to a sensitivity analysis when the success of
      root canal therapy and the risk of damage to the adjacent tooth were varied. The
      RPD for both the molar and incisor was the favored treatment based on a cost
      utility (3.85 and 2.74 CND$ per year of tooth saved respectively) and cost
      benefit analysis (0.92 to 0.60 CND$ of cost per $ of benefit, respectively) for a
      prosthetic clinical survival of 5-years. CONCLUSION: The position of the
      abscessed tooth and the amount of insurance coverage influences the utility and
      rank assigned by patients to the different treatment options. STI and CDB have
      optimal EUVs for a 5-year survival outcome, and RPD has significantly lower cost
      providing the better cost:benefit ratio.

PMID- 18053268
TI  - Use pattern of maternal health services and determinants of skilled care during
      delivery in Southern Tanzania: implications for achievement of MDG-5 targets.
AB  - BACKGROUND: Almost two decades since the initiation of the Safe motherhood
      Initiative, Maternal Mortality is still soaring high in most developing
      countries. In 2000 WHO estimated a life time risk of a maternal death of 1 in 16
      in Sub- Saharan Africa while it was only 1 in 2800 in developed countries. This
      huge discrepancy in the rate of maternal deaths is due to differences in access
      and use of maternal health care services. It is known that having a skilled
      attendant at every delivery can lead to marked reductions in maternal mortality.
      For this reason, the proportion of births attended by skilled health personnel is
      one of the indicators used to monitor progress towards the achievement of the MDG
      5 of improving maternal health. METHODS: Cross sectional study which employed
      quantitative research methods. RESULTS: We interviewed 974 women who gave birth
      within one year prior to the survey. Although almost all (99.8%) attended ANC at
      least once during their last pregnancy, only 46.7% reported to deliver in a
      health facility and only 44.5% were assisted during delivery by a skilled
      attendant. Distance to the health facility (OR = 4.09 (2.72-6.16)), discussion
      with the male partner on place of delivery (OR = 2.37(1.75-3.22)), advise to
      deliver in a health facility during ANC (OR = 1.43 (1.25-2.63)) and knowledge of
      pregnancy risk factors (OR 2.95 (1.65-5.25)) showed significant association with
      use of skilled care at delivery even after controlling for confounding factors.
      CONCLUSION: Use of skilled care during delivery in this district is below the
      target set by ICPD + of attaining 80% of deliveries attended by skilled personnel
      by 2005. We recommend the following in order to increase the pace towards
      achieving the MDG targets: to improve coverage of health facilities, raising
      awareness for both men and women on danger signs during pregnancy/delivery and
      strengthening counseling on facility delivery and individual birth preparedness.

PMID- 18053269
TI  - The role of horizontal transfer in the evolution of a highly variable
      lipopolysaccharide biosynthesis locus in xanthomonads that infect rice, citrus
      and crucifers.
AB  - BACKGROUND: Lipopolysaccharide (LPS) is a pathogen associated molecular pattern
      (PAMP) of animal and plant pathogenic bacteria. Variation at the interstrain
      level is common in LPS biosynthetic gene clusters of animal pathogenic bacteria.
      This variation has been proposed to play a role in evading the host immune
      system. Even though LPS is a modulator of plant defense responses, reports of
      interstrain variation in LPS gene clusters of plant pathogenic bacteria are rare.
      RESULTS: In this study we report the complete sequence of a variant 19.9 kb LPS
      locus present in the BXO8 strain of Xanthomonas oryzae pv. oryzae (Xoo), the
      bacterial blight pathogen of rice. This region is completely different in size,
      number and organization of genes from the LPS locus present in most other strains
      of Xoo from India and Asia. Surprisingly, except for one ORF, all the other ORFs
      at the BXO8 LPS locus are orthologous to the genes present at this locus in a
      sequenced strain of X. axonopodis pv. citri (Xac; a pathogen of citrus plants).
      One end of the BXO8 LPS gene cluster, comprised of ten genes, is also present in
      the related rice pathogen, X. oryzae pv. oryzicola (Xoc). In Xoc, the remainder
      of the LPS gene cluster, consisting of seven genes, is novel and unrelated to LPS
      gene clusters of any of the sequenced xanthomonads. We also report substantial
      interstrain variation suggestive of very recent horizontal gene transfer (HGT) at
      the LPS biosynthetic locus of Xanthomonas campestris pv. campestris (Xcc), the
      black rot pathogen of crucifers. CONCLUSION: Our analyses indicate that HGT has
      altered the LPS locus during the evolution of Xanthomonas oryzae pathovars and
      suggest that the ancestor of all Xanthomonas oryzae pathovars had an Xac type of
      LPS gene cluster. Our finding of interstrain variation in two major xanthomonad
      pathogens infecting different hosts suggests that the LPS locus in plant
      pathogenic bacteria, as in animal pathogens, is under intense diversifying
      selection.

PMID- 18053270
TI  - Association of autism with polymorphisms in the paired-like homeodomain
      transcription factor 1 (PITX1) on chromosome 5q31: a candidate gene analysis.
AB  - BACKGROUND: Autism is a complex, heterogeneous, behaviorally-defined disorder
      characterized by disruptions of the nervous system and of other systems such as
      the pituitary-hypothalamic axis. In a previous genome wide screen, we reported
      linkage of autism with a 1.2 Megabase interval on chromosome 5q31. For the
      current study, we hypothesized that 3 of the genes in this region could be
      involved in the development of autism: 1) paired-like homeodomain transcription
      factor 1 (PITX1), which is a key regulator of hormones within the pituitary
      hypothalamic axis, 2) neurogenin 1, a transcription factor involved in
      neurogenesis, and 3) histone family member Y (H2AFY), which is involved in X
      chromosome inactivation in females and could explain the 4:1 male:female gender
      distortion present in autism. METHODS: A total of 276 families from the Autism
      Genetic Resource Exchange (AGRE) repository composed of 1086 individuals
      including 530 affected children were included in the study. Single nucleotide
      polymorphisms tagging the three candidate genes were genotyped on the initial
      linkage sample of 116 families. A second step of analysis was performed using
      tightly linked SNPs covering the PITX1 gene. Association was evaluated using the
      FBAT software version 1.7.3 for single SNP analysis and the HBAT command from the
      same package for haplotype analysis respectively. RESULTS: Association between
      SNPs and autism was only detected for PITX1. Haplotype analysis within PITX1
      showed evidence for overtransmission of the A-C haplotype of markers rs11959298 -
      rs6596189 (p = 0.0004). Individuals homozygous or heterozygous for the A-C
      haplotype risk allele were 2.54 and 1.59 fold more likely to be autistic than
      individuals who were not carrying the allele, respectively. CONCLUSION: Strong
      and consistent association was observed between a 2 SNPs within PITX1 and autism.
      Our data suggest that PITX1, a key regulator of hormones within the pituitary
      hypothalamic axis, may be implicated in the etiology of autism.

PMID- 18053271
TI  - Prevalence of transfusion transmitted virus (TTV) genotypes among HCC patients in
      Qaluobia governorate.
AB  - BACKGROUND: Transfusion Transmitted virus (TTV) is a novel single-stranded DNA
      virus that was identified in patients with post-transfusion hepatitis of non-A-G
      type. Clinical significance of TTV infection was analyzed in Egyptian
      hepatocellular carcinoma (HCC) patients. The present study attempted to clarify
      these issues in Egypt, particularly in Qaluobia governorate, a country known for
      its high endemicity of liver disease and hepatotropic viruses. METHODS: TTV are
      determined in the serum of 60 samples obtained from HCC and liver cirrhosis (LC)
      patients and 30 healthy individuals. TTV DNA is amplified by nested-PCR with TTV
      specific mixed primers derived from the conserved open reading frame 1 (ORF1)
      region followed by digestion with restriction enzyme. Using the enzymes HaeIII,
      DraI, EcoRI and PstI, we are able to distinguish between the four TTV genotypes.
      RESULTS: The positive rate of TTV detection was 46.7%, 40% and 36.7% among HCC,
      LC patients and healthy individuals respectively. The more prevalence genotype
      was detected in the positive serum samples was genotype 1 (35.7%) in HCC
      patients, (50%) in LC and (63.3%) in healthy individuals, Genotype 5 (21.4%),
      (25.5%) and (18.2%) in HCC, LC and healthy individuals respectively. DISCUSSION:
      This study indicates that TTV is commonly present in adult patients with HCC and
      LC as well as healthy individuals. The most prevalence TTV genotype is genotype
      1. It seems that the infection neither contribute to the severity of liver
      disease no to the causation of HCC.

PMID- 18053272
TI  - Activation of middle-ear muscles by transcranial magnetic stimulation.
AB  - OBJECTIVES: To evaluate the reliability of transcranial magnetic stimulation in
      eliciting admittance changes due to activation of middle-ear muscles. METHODS:
      Admittance changes induced by transcranial magnetic stimulation at the inion were
      evaluated in eight normal subjects, two subjects with prelingual deafness and 22
      patients suffering from other otological disorders characterised by absence of
      acoustic reflex. RESULTS: Responses showed a predominant negative peak in normal
      ears. Two small positive components, one preceding and the other following the
      negative deflection, were less consistently elicited. Only a positive wave was
      detected in otosclerotic subjects. Patients with tympanic membrane perforation or
      previous tympanoplasty with ossicular discontinuity did not show any response.
      CONCLUSIONS: Transcranial magnetic stimulation is able to activate both stapedius
      and tensor tympani muscles. In conjunction with admittance audiometry, it may
      represent a method of exploring the mechanics of the middle ear when acoustic
      reflex testing is not reliable. It can be helpful in the confirmation of stapes
      fixation when a severe to profound hearing loss is present.

PMID- 18053273
TI  - The elimination of Chagas' disease from Brazil.
AB  - On 9 June 2006 the Pan American Health Organization (PAHO) presented the Minister
      of Health of Brazil with the International Elimination of Transmission of Chagas'
      Disease Certificate. This act was the culmination of an intensive process that
      began in 1991 with the Southern Cone Initiative, a joint agreement between the
      governments of Argentina, Bolivia, Brazil, Chile, Paraguay, Uruguay and Peru, to
      control Chagas' disease by the elimination of the main vector, Triatoma
      infestans. This initiative has been highly successful and the prevalence area of
      the vector diminished rapidly in the last years. As a consequence, the current
      seroprevalence in children aged between 0 and 5 years is of the order of 10(-5),
      a clear indication that transmission, if it is occurring, is only accidental. In
      this review I calculate the basic reproduction number, R0, for Chagas' disease
      and demonstrate that its relatively low value (1.25) explains why vectorial
      transmission was interrupted relatively easily. In addition, I used a
      mathematical model to forecast how long the remaining cases of the disease, as
      well as the additional vertically transmitted cases will last.

PMID- 18053274
TI  - The seasonality of human cryptosporidiosis in New Zealand.
AB  - In New Zealand human cryptosporidiosis demonstrates spring and autumn peaks of
      incidence with the spring peak being three times greater in magnitude than the
      autumn peak. The imbalance between the two peaks is notable, and may be
      associated with the high livestock density in New Zealand. In the summer and
      autumn the cryptosporidiosis rate was positively associated with temperatures in
      the current and previous month, highlighting the importance of outdoor recreation
      to transmission. No associations between spring incidence and weather were found
      providing little support for the importance of drinking-water pathways. Imported
      travel cases do not appear to be an important factor in the aetiology of
      cryptosporidiosis in New Zealand.

PMID- 18053275
TI  - The prevalence of iodine deficiency in women of reproductive age in the United
      States of America.
AB  - OBJECTIVE: To review the iodine status of women as assessed through National
      Health and Nutrition Examination Surveys from 1971 to 2002. DESIGN AND SETTING:
      National normative estimates of iodine status of the civilian, non
      institutionalized population in the United States of America. SUBJECTS: Women of
      reproductive age and pregnant women. RESULTS: In the United States of America,
      iodine began to be added to the diet in the 1920s. An excessive iodine intake was
      documented by the first National Health and Nutrition Examination Survey (NHANES
      I) in the 1970s which reported a median urinary iodine (UI) concentration of 320
      microg l-1. In the NHANES III survey, conducted between 1988 and 1994, the median
      UI concentration had decreased to 145 microg l-1, while 14.9% of women aged 15-44
      years and 6.9% of pregnant women had a UI concentration 50 microg l-1. The
      concentrations of serum T4 and thyroid-stimulating hormone of women with a low UI
      concentration did not, however, indicate an iodine deficiency. CONCLUSIONS:
      Further studies of the association between iodine excretion and biochemical and
      physiological changes should be undertaken to better understand women's needs for
      iodine and to develop criteria to monitor them in pregnancy. Because of the
      potential harm caused by iodine deficiency during pregnancy, we support the use
      of iodine supplements for all pregnancies while these data are being collected.

PMID- 18053277
TI  - The importance of iodine nutrition during pregnancy.
AB  - OBJECTIVE: To examine the importance of iodine nutrition during pregnancy.
      DESIGN: Review of existing literature of iodine in pregnancy. SETTING: Population
      surveys and metabolic studies. SUBJECTS: Pregnant women. RESULTS: The main
      changes in thyroid function associated with pregnancy are due to an increase in
      hormone requirements that begin in the first trimester of gestation. This
      increase can only be met by a proportional increase in hormone production,
      something that depends directly upon the availability of iodine. When dietary
      iodine is lacking, an adequate physiological adaptation is difficult to achieve
      and is progressively replaced by pathological alterations that occur in parallel
      with the degree and duration of iodine deprivation. CONCLUSIONS: Iodine
      prophylaxis should be given systematically to women during pregnancy. In most
      public health programmes dealing with the correction of iodine deficiency
      disorders, iodised salt has been used as the preferred means to deliver iodine to
      households. Iodised salt, however, is not the ideal means of delivering iodine in
      the specific instances of pregnancy, breast-feeding and complementary feeding
      because of the need to limit salt intake during these periods. In European
      countries, presently it is proposed that iodine is given to pregnant women and
      breast-feeding mothers by systematically administering multivitamin tablets
      containing iodine in order to reach the recommended dietary allowance of 250
      microg iodine day-1.

PMID- 18053278
TI  - Evaluating iodine deficiency in pregnant women and young infants-complex
      physiology with a risk of misinterpretation.
AB  - OBJECTIVE: To review methods for evaluating iodine deficiency in pregnant women
      and young infants and to discuss factors to be considered in the interpretation
      of their results. DESIGN: Review of the literature regarding the various methods
      available for assessing iodine status. SETTING: Population surveys and research
      studies. SUBJECTS: Pregnant women and young infants. RESULTS: Several factors to
      consider when assessing iodine status in pregnant women and young infants
      include: 1) the urinary iodine (UI) concentration (microg l-1) is not
      interchangeable with 24 h UI excretion (microg per 24 h); 2) the concentration of
      iodine in a spot or casual urine sample cannot be used to diagnose iodine
      deficiency in an individual; 3) a moderate fall in the concentration of serum
      free T4 during pregnancy is not a sign of maternal iodine deficiency; 4) an
      increase in the concentration of serum thyroglobulin (Tg) during pregnancy is not
      a sign of maternal iodine deficiency; 5) a higher concentration of TSH and Tg in
      cord blood than in maternal blood is not a sign of iodine deficiency in the
      mother or neonate; and 6) thyroid function in a full-term foetus, a neonate or a
      small child is not more sensitive to a mild iodine deficiency than in the mother.
      CONCLUSIONS: If the iodine status of pregnant women and small children is not to
      be misjudged, the above six factors need to be taken into account.

PMID- 18053280
TI  - Iodine deficiency and brain development in the first half of pregnancy.
AB  - An inadequate supply of iodine during gestation results in damage to the foetal
      brain that is irreversible by mid-gestation unless timely interventions can
      correct the accompanying maternal hypothyroxinemia. Even mild to moderate
      maternal hypothyroxinemia may result in suboptimal neurodevelopment. This review
      mainly focuses on iodine and thyroid hormone economy up to mid-gestation, a
      period during which the mother is the only source for the developing brain of the
      foetus. The cerebral cortex of the foetus depends on maternal thyroxine (T4) for
      the production of the 3',3,5-tri-iodothyronine (T3) for nuclear receptor-binding
      and biological effectiveness. Maternal hypothyroxinemia early in pregnancy is
      potentially damaging for foetal brain development. Direct evidence has been
      obtained from experiments on animals: even a relatively mild and transient
      hypothyroxinemia during corticogenesis, which takes place mostly before mid
      gestation in humans, affects the migration of radial neurons, which settle
      permanently in heterotopic locations within the cortex and hippocampus.
      Behavioural defects have also been detected. The conceptus imposes important
      early changes on maternal thyroid hormone economy that practically doubles the
      amount of T4 secreted something that requires a concordant increase in the
      availability of iodine, from 150 to 250-300 microg I day- 1. Women who are unable
      to increase their production of T4 early in pregnancy constitute a population at
      risk for having children with neurological disabilities. As a mild to moderate
      iodine deficiency is still the most widespread cause of maternal
      hypothyroxinemia, the birth of many children with learning disabilities may be
      prevented by advising women to take iodine supplements as soon as pregnancy
      starts, or earlier if possible, in order to ensure that their requirements for
      iodine are met.

PMID- 18053281
TI  - Iodine requirements during pregnancy, lactation and the neonatal period and
      indicators of optimal iodine nutrition.
AB  - OBJECTIVE: This paper re-evaluates the requirements for iodine during pregnancy,
      lactation and the neonatal period, and formulates original proposals for the
      median concentrations of urinary iodine (UI) that indicate optimal iodine
      nutrition during these three critical periods of life. This paper also discusses
      the measurements that are used to explore thyroid functions during the same
      periods. DESIGN: An extensive and critical review of the literature on thyroid
      physiopathology during the perinatal period. SETTING: Human studies conducted in
      various regions throughout the world. SUBJECTS: Pregnant women, lactating women,
      and newborns. RESULTS: The following proposals are made after extensive review of
      the literature: the requirement for iodine by the mother during pregnancy is 250
      300 microg day-1; during lactation the requirement is 225-350 microg day-1; and
      during the neonatal period the requirement of the infant is 90 microg day-1. The
      median UI that indicates an optimal iodine nutrition during these three periods
      should be in the range of 150-230 microg day-1. These figures are higher than
      recommended to date by the international agencies. CONCLUSIONS: Pregnant women
      and young infants, but especially the second group, are more sensitive to the
      effects of an iodine deficiency (ID) than the general population because their
      serum thyroid-stimulating hormone (TSH) and thyroxine are increased and
      decreased, respectively, for degrees of ID that do not seem to affect thyroid
      function in the general population. Systematic neonatal thyroid screening using
      primary TSH could be the most sensitive indicator to monitor the process of ID
      control.

PMID- 18053283
TI  - The impact of iodised salt or iodine supplements on iodine status during
      pregnancy, lactation and infancy.
AB  - OBJECTIVES: Monitoring of iodine status during pregnancy, lactation and infancy
      is difficult as there are no established reference criteria for urinary iodine
      concentration (UI) for these groups; so it is uncertain whether iodized salt
      programs meet the needs of these life stages. DESIGN AND SUBJECTS: The method
      used in this paper was: 1) to estimate the median UI concentration that reflects
      adequate iodine intake during these life stages; and 2) to use these estimates in
      a review of the literature to assess whether salt iodisation can control iodine
      deficiency in pregnant and lactating women, and their infants. RESULTS: For
      pregnancy, recommended mean daily iodine intakes of 220-250 microg were estimated
      to correspond to a median UI concentration of about 150 microg l- 1, and larger
      surveys from the iodine sufficient countries have reported a median UI in
      pregnant women > or = 140 microg l- 1. Iodine supplementation in pregnant women
      who are mild-to-moderately iodine deficient is beneficial, but there is no clear
      affect on maternal or newborn thyroid hormone levels. In countries where the
      iodine intake is sufficient, most mothers have median breast milk iodine
      concentration (BMIC) greater than the concentration (100-120 microg l- 1)
      required to meet an infant's needs. The median UI concentration during infancy
      that indicates optimal iodine nutrition is estimated to be > or = 100 microg l-
      1. In iodine-sufficient countries, the median UI concentration in infants ranges
      from 90-170 microg l- 1, suggesting adequate iodine intake in infancy.
      CONCLUSIONS: These findings suggest pregnant and lactating women and their
      infants in countries with successful sustained iodised salt programs have
      adequate iodine status.

PMID- 18053284
TI  - Iodine nutrition in pregnancy and lactation in Iran.
AB  - OBJECTIVE: To describe studies evaluating urinary iodine excretion during
      pregnancy and lactation in women living in cities with adequate or more than
      adequate iodine intake. DESIGN: Cross-sectional study conducted between 1996 and
      1998 in pregnant women and a study of lactating women conducted in 2003. SETTINGS
      AND SUBJECTS: Pregnant women attending prenatal clinics in four cities in the
      Islamic Republic of Iran. Urinary iodine excretion and thyroid volume was
      measured in 403 women. In a second study, 100 lactating women from Taleghani
      Hospital in Gorgan, Iran were evaluated for thyroid size, and both urinary and
      breast milk iodine concentrations were determined. RESULTS: In Rasht city, 84% of
      pregnant women had a urinary iodine concentration of > or = 200 microg l-1, while
      in the other cities this percentage ranged from 45 to 55%. When data were
      combined for the cities of Ilam, Isfahan and Tehran, where women have an adequate
      or more than adequate median urinary iodine concentration, 51% of pregnant women
      had a urinary iodine concentration less than that recommended during pregnancy.
      In Rasht, where the median urinary iodine concentration indicates an excessive
      iodine intake, 15.4% of pregnant women had a urinary iodine concentration < 200
      microg l-1. The mean urinary iodine concentration in lactating women was 250
      microg l-1, and 16% of women had a urinary iodine concentration < 100 microg l-1.
      Grade 1 goitre was present in 8% of lactating women, and another 8% had grade 2
      goitre. CONCLUSIONS: Findings of this study call for further attention to iodine
      intake during pregnancy and lactation. The currently recommended intake of iodine
      through universal salt iodisation may not be adequate for pregnant and lactating
      women, and supplementation during pregnancy and lactation should be further
      considered in light of the latest recommendations.

PMID- 18053285
TI  - Iodine nutrition of pregnant and lactating women in Hong Kong, where intake is of
      borderline sufficiency.
AB  - OBJECTIVE: To describe the iodine nutrition of pregnant and lactating women in
      Hong Kong, where intake is of borderline sufficiency. DESIGN: Review of cross
      sectional and prospective studies. SETTING: China, Hong Kong Special
      Administrative Region (SAR). SUBJECTS: Pregnant and lactating women. RESULTS:
      Studies of pregnant women in Hong Kong SAR have revealed an increase in the
      urinary iodine (UI) concentration as pregnancy advances. A significant percentage
      of women had a sub-normal serum thyroid hormone concentration at full term.
      Although iodine is concentrated by the mammary gland, 19% of all mothers had low
      iodine concentrations in their breast milk. The moderate correlation between the
      concentrations of iodine in breast milk and urine suggests that an adequate
      maternal urinary iodine concentration cannot reliably indicate that an infant is
      getting enough iodine in breast milk. Therefore, some breast-fed infants may
      still be at risk of low iodine intake, and additional iodine supplements, other
      than salt iodisation, would be warranted in this population. CONCLUSIONS: The
      currently recommended intake of iodine through universal salt iodisation may not
      be adequate for pregnant and lactating women, and supplementation during
      pregnancy and lactation should be further considered in light of the latest
      recommendations.

PMID- 18053286
TI  - Iodine deficiency in pregnant women and neonates in Thailand.
AB  - OBJECTIVE: To present data on the relationship between the concentration of
      thyroid-stimulating hormone (TSH) in whole blood or serum from neonates and the
      concentration of iodine in their mother's urine collected at birth to contribute
      to the contention that the recommended iodine intake during pregnancy should be
      increased. DESIGN AND SETTING: Data were provided by current programmes of
      neonatal screening of congenital hypothyroidism in Bangkok and rural areas of
      Thailand. SUBJECTS: A total of 5144 cord serum samples were collected in 2003 and
      measured for TSH concentrations. Paired samples of blood and urine were collected
      in 2000 from 203 infants and their mothers and from 1182 infant-mother pairs in
      2002-03 in six rural provinces. Iodine was measured in the urine and TSH was
      measured in cord serum. RESULTS: The urinary iodine concentration of mothers in
      rural Thailand is adequate, with a median of 103 microg l-1. However, in 2000,
      the median urinary iodine concentration of mothers in Bangkok was only 85 microg
      l-1. The concentration of TSH in whole blood collected on filter paper from
      neonates was not sensitive enough to be used as a monitoring tool for iodine
      nutrition in the neonates, as there was no relationship with the concentration of
      iodine in the urine of the children's mothers. This was in contrast to the
      concentration of TSH in serum collected from cord blood. CONCLUSIONS: Several
      conclusions were drawn from this data: 1) Neonatal TSH screening using whole
      blood collected from a heel prick at 3 days of age is not sensitive enough to
      assess the iodine nutrition of neonates; 2) Neonatal TSH screening using cord
      sera can be used to assess iodine nutrition in neonates; 3) The optimum median
      maternal urinary iodine concentration in Thailand appears to be 103 microg l-1;
      4) The criteria proposed by WHO, UNICEF, and ICCIDD to assess iodine nutrition
      using data on neonatal TSH concentrations should be reassessed; and 5) Neonatal
      TSH screening can be effectively performed by collecting cord serum in district
      hospitals in Thailand.

PMID- 18053287
TI  - Prevention and control of iodine deficiency in pregnant and lactating women and
      in children less than 2-years-old: conclusions and recommendations of the
      Technical Consultation.

PMID- 18053288
TI  - Iron-regulatory proteins: molecular biology and pathophysiological implications.
AB  - Iron is required for key cellular functions, and there is a strong link between
      iron metabolism and important metabolic processes, such as cell growth, apoptosis
      and inflammation. Diseases that are directly or indirectly related to iron
      metabolism represent major health problems. Iron-regulatory proteins (IRPs) 1 and
      2 are key controllers of vertebrate iron metabolism and post-transcriptionally
      regulate expression of the major iron homeostasis genes. Here we discuss how
      dysregulation of the IRP system can result from both iron-related and unrelated
      effectors and explain how this can have important pathological consequences in
      several human disorders.

PMID- 18053289
TI  - Prevalence of self-reported sleep disturbance among older adults and the
      association of disturbed sleep with service demand and medical conditions.
AB  - OBJECTIVE: This cross-sectional study investigated the prevalence of disturbed
      sleep and the association of disturbed sleep with medical conditions and service
      use among older adults. METHODS: A sample of 6961 household residents aged 60 and
      over was recruited from a population-based random sample. Each subject was
      examined in a face-to-face interview. RESULTS: The overall prevalence of
      disturbed sleep was 33.7%, with the condition being more prevalent in women
      (37.2%) than in men (27.4%). The overall rate of medical consultations was 78%,
      and higher in those with sleep disturbance (males 73% vs 27%; females 80% vs 20%)
      compared to persons without disturbed sleep. The overall rate of hospitalizations
      was 20.2%. In logistic regression analyses, being female, of low income, low
      education, younger age, with psychiatric morbidity, pneumonia, urinary infection,
      dermatological problems and/or hypertension were significantly associated with
      self-reported sleep disturbance. Ethnicity, civil status or outpatient visits in
      the previous six months and hospitalizations in the previous year were not
      associated with self-reported sleep disturbance. CONCLUSION: Self-reported sleep
      disturbance was a frequent problem in the study population and was associated
      with gender, income, education, lower age and medical conditions. There was no
      association between sleep problems and use of medical services in the surveyed
      population.

PMID- 18053290
TI  - Attachment style and anxiety in carers of people with Alzheimer's disease:
      results from the LASER-AD study.
AB  - BACKGROUND: Preliminary evidence indicates that the quality of the carer-care
      recipient relationship predicts those carers most at risk from anxiety.
      Attachment style is related to higher carer burden, psychological morbidity and
      increased care recipient institutionalization. We tested, for the first time, the
      hypothesis that carer burden and the coping strategies used mediate a
      relationship between attachment style and anxiety. METHODS: We interviewed 83
      people with Alzheimer's disease and their family carers, originally recruited for
      a larger community study. Carers filled in a validated measure about their
      attachment style, the Hospital Anxiety and Depression Scale, the COPE to measure
      coping strategies, and the Zarit-Burden interview. RESULTS: More avoidant
      attachment (beta = 0.28) and less secure attachment (beta = -0.32) predicted
      anxiety. After adding coping strategies to the equation, the relationship with
      avoidant attachment (beta = 0.15) was no longer significant, and that with less
      secure attachment was reduced (beta = -0.23). A well-fitting structural equation
      model supported our finding that dysfunctional coping mediated the relationship
      between attachment style and anxiety. CONCLUSION: Carers who were less secure or
      more avoidantly attached reported higher anxiety. Interventions that aim to
      modify coping strategies have shown promise in reducing carer anxiety. Our
      finding that coping strategies also appear partially to explain the excess of
      anxiety among less securely attached carers suggests they are likely to benefit
      from such interventions.

PMID- 18053291
TI  - Specific tyrosine phosphorylation induced in Schistosoma mansoni miracidia by
      haemolymph from schistosome susceptible, but not resistant, Biomphalaria
      glabrata.
AB  - Molecular interplay during snail-schistosome interactions is poorly understood
      and there is much to discover concerning the effect of snail host molecules on
      molecular processes in schistosomes. Using the Biomphalaria glabrata -
      Schistosoma mansoni host-parasite system, the effects of exposure to haemolymph,
      derived from schistosome-resistant and susceptible snail strains, on protein
      tyrosine phosphorylation in miracidia have been investigated. Western blotting
      revealed several tyrosine phosphorylated proteins in this larval stage. Exposure
      of miracidia to haemolymph from susceptible snails for 60 min resulted in a
      striking, 5-fold, increase in the tyrosine phosphorylation of a 56 kDa (p56) S.
      mansoni protein. In contrast, haemolymph from resistant snails had little effect
      on protein tyrosine phosphorylation levels in miracidia. Confocal microscopy
      revealed that tyrosine phosphorylation was predominantly associated with proteins
      present in the tegument. Finally, treatment of miracidia with the tyrosine kinase
      inhibitor genistein significantly impaired their development into primary
      sporocysts. The results open avenues for research that focus on the potential
      importance of phospho-p56 to the outcome of schistosome infection in snails, and
      the significance of protein tyrosine kinase-mediated signalling events to the
      transformation of S. mansoni larvae.

PMID- 18053292
TI  - Effects of water flow on the infection dynamics of Myxobolus cerebralis.
AB  - Myxobolus cerebralis, the myxozoan parasite responsible for whirling disease in
      salmonid fishes, has a complex life-cycle involving an invertebrate host and 2
      spore stages. Water flow rate is an environmental variable thought to affect the
      establishment and propagation of M. cerebralis; however, experimental data that
      separates flow effects from those of other variables are scarce. To compare how
      this parameter affected parasite infection dynamics and the invertebrate and
      vertebrate hosts, dead, infected fish were introduced into a naive habitat with
      susceptible hosts under 2 experimental flow regimes: slow (0 x 02 cm/s) and fast
      (2 x 0 cm/s). Throughout the 1-year study, uninfected fry were held in both
      systems, the outflows were screened weekly for spores and the annelid populations
      were monitored. We found clear differences in prevalence of infection in the
      worms, prevalence and severity of infection in the fish, and host survival. Both
      flows provided environments in which M. cerebralis could complete its life-cycle;
      however, both the parasite and its invertebrate host proliferated to a greater
      extent in the slow flow environment over the 1-year study period. This finding is
      of significance for aquatic systems where the flow rate can be manipulated, and
      should be incorporated into risk analysis assessments.

PMID- 18053293
TI  - Dietary intake and different types of physical activity: full-day energy
      expenditure, occupational and leisure-time.
AB  - OBJECTIVE: To describe the relationship between dietary intake and different
      levels and types of physical activity (PA). DESIGN: Cross-sectional evaluation of
      the EPIPorto study. Energy expenditure (metabolic energy equivalent tasks) and
      dietary intake during the past year were assessed using a PA questionnaire and a
      semi-quantitative food-frequency questionnaire, respectively. SETTING:
      Representative sample of adults in Porto, Portugal. SUBJECTS: Data were analysed
      for 2404 Portuguese Caucasian adults, aged between 18 and 92 years. RESULTS: For
      total PA, males who were active had significantly higher mean intake of energy
      (10.76 (2570.7) vs. 9.78 (2336.9) MJ/d (kcal/d), P < 0.001) and lower level of
      protein consumption (16.9 vs. 17.6 % of energy, P < 0.001) compared with
      sedentary males. In males, the association between total PA and energy intake
      remained after adjustment for age, education and body mass index. Similar results
      were observed when occupational activity was analysed. Concerning the energy
      expended in leisure time, in both genders, after adjustment for the previously
      described variables, a significant positive association was found between PA and
      intake of vitamin C (g/d): beta = 0.12, 99 % confidence interval (CI) 0.02, 0.21
      for females and beta = 0.13, 99 % CI 0.03, 0.22 for males. Leisure-time activity
      in females was also positively associated with intakes of fibre, vitamin E,
      folate, calcium and magnesium, and negatively associated with saturated fat.
      CONCLUSIONS: Higher levels of PA in leisure time were associated with higher
      intakes of micronutrients and lower intakes of saturated fat, particularly in
      females. For total and occupational PA, similar nutrient intake was observed
      between active and sedentary individuals.

PMID- 18053295
TI  - Reproducibility of systematic literature reviews on food, nutrition, physical
      activity and endometrial cancer.
AB  - OBJECTIVE: Despite the increasing dependence on systematic reviews to summarise
      the literature and to issue public health recommendations, the formal assessment
      of the reliability of conclusions emerging from systematic reviews has received
      little attention. The main goal of the present study was to evaluate whether two
      independent centres, in two continents, draw similar conclusions regarding the
      association of food, nutrition and physical activity and endometrial cancer, when
      provided with the same general instructions and with similar resources. DESIGN:
      The assessment of reproducibility concentrated on four main areas: (1) paper
      search and selection; (2) assignment of study design; (3) inclusion of papers;
      and (4) individual studies selected for meta-analysis and the summary risk
      estimate obtained. RESULTS: In total 310 relevant papers were identified, 166 (54
      %) were included by both centres. Of the remaining 144 papers, 72 (50 %) were
      retrieved in the searches of one centre and not the other (54 in centre A, 18 in
      centre B) and 72 were retrieved in both searches but regarded as relevant by only
      one of the centres (52 in centre A, 20 in centre B). Of papers included by both
      centres, 80 % were allocated the same study design. Agreement for inclusion of
      cohort-type and case-control studies was about 63% compared with 50% or less for
      ecological and case series studies. The agreement for inclusion of 138 'key'
      papers was 87 %. Summary risk estimates from meta-analyses were similar.
      CONCLUSIONS: Transparency of process and explicit detailed procedures are
      necessary parts of a systematic review and crucial for the reader to interpret
      its findings.

PMID- 18053294
TI  - Carotenoid intakes, assessed by food-frequency questionnaires (FFQs), are
      associated with serum carotenoid concentrations in the Jackson Heart Study:
      validation of the Jackson Heart Study Delta NIRI Adult FFQs.
AB  - OBJECTIVES: Intake and status of carotenoids have been associated with chronic
      disease. The objectives of this study were to examine the association between
      carotenoid intakes as measured by two regional food-frequency questionnaires
      (FFQs) and their corresponding measures in serum, and to report on dietary food
      sources of carotenoids in Jackson Heart Study (JHS) participants. DESIGN: Cross
      sectional analysis of data for 402 African American men and women participating
      in the Diet and Physical Activity Sub-Study (DPASS) of the JHS. RESULTS: Mean
      serum carotenoid concentrations and intakes in this population were comparable to
      those reported for the general US population. After adjustment for covariates,
      correlations between serum and dietary measures of each carotenoid, for the
      average of the recalls (deattenuated), the short FFQ and the long FFQ,
      respectively, were: 035 and 0-carotene; 026 and 0-carotene; 017 and 0-carotene;
      034 and 0-cryptoxanthin; 015 and 037, 014 for lycopene. Major dietary sources of 
      carotene and lutein plus zeaxanthin, mustard, turnip and collard greens; of beta
      cryptoxanthin, orange juice; and of lycopene, tomato juice. CONCLUSIONS: On
      average, carotenoid intakes and serum concentrations are not lower in this
      southern African American population than the general US population. The two
      regional FFQs developed for a southern US population and used as dietary
      assessment tools in the JHS appear to provide reasonably valid information for
      most of these carotenoids.

PMID- 18053296
TI  - Kinetic disposition of albendazole in goats subclinically infected with
      gastrointestinal nematodes vis-a-vis naive animals following oral and
      intraruminal administration.
AB  - The influence of subclinical nematodosis on the kinetic disposition of
      albendazole was evaluated in goats following oral and intraruminal
      administration. The disposition curves of its metabolites indicated increased
      uptake of the drug in parasitized goats following intraruminal compared to oral
      dosing (P < 0.05). The midpoint for the pharmacologically active metabolite,
      albendazole sulphoxide, in the circulatory compartment was around 0.6 mug ml- 1
      both in parasitized and naive goats. The period of exposure to this concentration
      was around 14 h (oral route), 18 h (intraruminal route) and 16 h (oral route), 17
      h (intraruminal route) in parasitized and naive goats, respectively. As the
      duration of exposure of parasites to the toxic concentration of the
      anthelmintically active metabolite was prolonged, it could be assumed that
      intraruminal delivery of the drug would improve the efficacy of albendazole in
      parasitized goats.

PMID- 18053297
TI  - Seasonal contamination of public squares and lawns by parasites with zoonotic
      potential in southern Brazil.
AB  - The presence of helminths and protozoans in public squares and lawns of the city
      of Maringa, southern Brazil, during winter and summer was assessed in order to
      evaluate their seasonal fluctuations in relation to edaphic and climatic factors.
      Samples were collected from January 2003 through June 2004 in 90% (13) of all
      public squares covered by sand, and in 30% (4) of all lawns used as leisure
      areas. The samples were analysed quantitatively by modified centrifugal-flotation
      and sedimentation in water techniques, and qualitatively by a method based on
      positive larval thermo-hydrotropism. Meteorological data were recorded, and
      physical, chemical and structural characteristics of the soil were analysed. One
      hundred and thirty samples of sand from squares, 65 in summer and 65 in winter,
      and 40 samples of grass from lawns, 20 in each season, were collected. All
      samples from lawns, 62 (95.38%) from squares in winter and 45 (69.23%) in summer,
      contained protozoans and/or helminths. Eggs of Toxocara spp. were the most
      frequently observed parasites in both winter and summer in squares (P < 0.0001)
      and in lawns (P = 0.6142), being equally distributed among the different
      locations (P = 0.2038). Species diversity was lower in winter; fewer parasites
      were found in summer. This region, with a tropical climate and a mild winter dry
      season, has favourable edaphic and climatic conditions for soil contaminants to
      persist year-round. In addition, the high frequency of animals such as dogs and
      cats and the poor sanitary measures in force made it possible for zoonoses to be
      transmitted in the public spaces.

PMID- 18053298
TI  - Glycogen catabolism enzymes and protein fractions in the third and fourth larval
      stages of Anisakis simplex.
AB  - Extracts of Anisakis simplex third (L3) and fourth (L4) larval stages were
      assayed for protein content and activity and properties of alpha-amylase,
      glucoamylase and glycogen phosphorylase. Protein content in L4 was twice that in
      L3. SDS-PAGE applied to both larval stages revealed 22 protein fractions in each,
      including five stage-specific fractions in each larval stage. The L3 extracts
      contained three amylase isoenzymes: alpha 1, alpha 2 and alpha 3; their molecular
      weights were 64, 29 and 21 kDa, respectively. Only one amylase isoenzyme (64 kDa)
      was found in the L4 extracts. Glycogen in L3 was found to be broken down mostly
      by hydrolysis because of low glycogen phosphorylase activity. The alpha-amylase
      activity in L4 was higher than that in L3 by half and the glycogen phosphorylase
      activity was ten times higher. In addition, the same enzymes isolated from L3 and
      L4 were found to differ in their properties. These differences could be
      manifestations of metabolic adaptations of A. simplex larvae to host switch from
      fish (L3) to mammals (L4), i.e. adaptations to a new habitat.

PMID- 18053299
TI  - The occurrence of Caryophyllaeus laticeps in the nase Chondrostoma nasus from
      Austrian rivers: possible anthropogenic factors.
AB  - Between April 2003 and November 2006 a total of 198 nase Chondrostoma nasus (L.)
      were examined for parasites from seven river sites in Austria. The selected sites
      showed different levels of anthropogenic alterations in river morphology ranging
      from pristine areas, with minor anthropogenic alterations, to strongly physically
      altered rivers. A variety of parasites were recovered from the skin, gills,
      swimbladder and eyes, with Caryophyllaeus laticeps (Pallas) being identified as
      the only cestode species occurring in the intestine. This is the first record of
      this species in nase in Austria. Caryophyllaeus laticeps was confined to the
      first 20% of the intestine, even in heavily infected hosts. The occurrence of C.
      laticeps within the fish population seems to be correlated with the degree of
      anthropogenic changes of the nase's habitat. In rivers with a high degree of
      ecological integrity or in rivers that are only partially dammed, C. laticeps is
      either absent in C. nasus or occurs with low prevalence (5.6-20%) and low mean
      intensity values (1.0-4.0). Where anthropogenic factors have changed the entire
      river into a reservoir, and fish cannot escape, the prevalence of infection with
      C. laticeps increases from 46.2 to 78.2% and the mean intensity from 8.8 to 17.2.

PMID- 18053300
TI  - Development of Fasciola hepatica in Lymnaea columella infected with miracidia
      derived from cattle and marmoset infections.
AB  - The development of Fasciola hepatica from two species of definitive hosts, i.e.
      cattle (Bos taurus) and a marmoset (Callithrix penicillata) in the snail Lymnaea
      columella was determined based on the production of rediae and cercariae and
      snail survival rate. More rediae and cercariae at 60-74 days post-infection were
      produced by snails infected by cattle-derived miracidia (cattle group) than by
      those infected by marmoset-derived miracidia (marmoset group). Among the L.
      columella parasitized by the marmoset group, the survival rate and the percentage
      of positive snails were higher than among those parasitized by the cattle group.
      Eggs of F. hepatica released in cattle faeces were significantly bigger than
      those released in marmoset faeces. Miracidia originating from parasites that
      completed their development in cattle were more efficient in infecting the
      intermediate host. These results suggest that vertebrate-host origin influences
      the eggs produced by the parasite and the infection rates in the snail host L.
      columella.

PMID- 18053301
TI  - Epidemiology of intestinal helminth parasites of dogs in Ibadan, Nigeria.
AB  - An epidemiological study of gastrointestinal helminths of dogs (Canis familiaris)
      in two veterinary clinics in Ibadan, Nigeria, was conducted between January 2001
      and December 2002. Faecal samples collected from 959 dogs were processed by
      modified Kato-Katz technique and then examined for helminth eggs. The results of
      the study showed that 237 (24.7%) of the dogs examined were infected with
      different types of helminths. The prevalences for the various helminth eggs
      observed were: Toxocara canis 9.0%, Ancylostoma spp. 17.9%, Toxascaris leonina
      0.6%, Trichuris vulpis 0.5%, Uncinaria stenocephala 0.4% and Dipylidium caninum
      0.2%. The faecal egg intensities, determined as mean egg count/gram of faeces (
      +/- SEM), were: T. canis 462.0 +/- 100.5, Ancylostoma spp. 54.1 +/- 8.6, T.
      leonina 0.8 +/- 0.4, T. vulpis 0.1 +/- 0.0, U. stenocephala 1.0 +/- 0.7 and D.
      caninum 0.2 +/- 0.1. Host age was found to be a significant factor with respect
      to the prevalence and intensity of T. canis and Ancylostoma spp. There was no
      significant difference in the prevalence of intestinal helminth parasites between
      male (27.0%) and female (22.5%) dogs (P>0.05). The prevalence of helminth
      parasites was significantly higher (P < 0.05) in the local breed (African
      shepherd) (41.2%) than in Alsatian dogs (16.2%) or in other exotic breeds
      (21.0%). Single parasite infections (85.7%) were more common than mixed
      infections (3.5%).

PMID- 18053302
TI  - Modification of gDNA extraction from soil for PCR designed for the routine
      examination of soil samples contaminated with Toxocara spp. eggs.
AB  - A modification of gDNA extraction was developed for the polymerase chain reaction
      (PCR) technique, intended for the detection and differentiation of Toxocara spp.
      eggs in soil or sediments. Sand samples from sandpits confirmed as being
      contaminated with Toxocara spp. eggs by the flotation technique were analysed by
      PCR. The use of proteinase K made it possible to obtain genomic DNA from the
      sample without needing to isolate eggs using flotation or to inactivate PCR
      inhibitors present in the sand. Specific primers in the PCR reaction allowed
      discrimination between T. canis and T. cati eggs. The modification simplified the
      procedure, thanks to eliminating the step of gDNA isolation from eggs, which is
      both laborious and difficult.

PMID- 18053303
TI  - Experimental infection of the cockroach Periplaneta americana with Toxocara canis
      and the establishment of patent infections in pups.
AB  - The possible role of the cockroach Periplaneta americana in the transmission of
      Toxocara canis eggs and larvae via faeces and tissue migration was studied.
      Cockroaches fed with 3 x 105 and 5 x 105 embryonated eggs were found to harbour
      viable eggs and larvae from days 1 to 5 post-infection (DPI). At necropsy on 5
      DPI, eggs and larvae were also recovered from the rectal contents but not from
      the tissues of cockroaches. In addition patent infections were established in
      pups fed on infected faeces of cockroaches, with eggs first appearing in the
      faeces of pups at 38 DPI. Adult worms of T. canis were also recovered at
      necropsy. Therefore the importance of cockroaches as good mechanical
      disseminators of ascarid eggs, especially T. canis, is discussed.

PMID- 18053304
TI  - In vitro nematicidal effects of medicinal plants from the Sierra de Huautla,
      Biosphere Reserve, Morelos, Mexico against Haemonchus contortus infective larvae.
AB  - Twenty extracts from plants from Sierra de Huautla Biosphere Reserve, Morelos,
      Mexico were evaluated against Haemonchus contortus infective larvae in an in
      vitro assay. The plant species evaluated were Bursera copallifera, B.
      grandifolia, Lippia graveolens, Passiflora mexicana, Prosopis laevigata, Randia
      echinocarpa and Urtica dioica. The plants were separated into their parts and
      macerated with different solvents (n-hexane, acetone, ethanol and methanol). An
      in vitro assay was used to evaluate the anthelmintic activity against unsheathed
      third stage H. contortus infective larvae. The experiment was carried out in 24
      well cell culture plates at room temperature with three replicates per treatment
      and using a concentration of 20 mg ml- 1. Ten 5 microl aliquots were taken from
      the corresponding wells and deposited on a slide for microscopical observation at
      24, 48, 72 and 96 h post-exposure. The evaluation criteria were based on the
      average numbers of live and/or dead larvae in the different treatments. Alive and
      dead larval numbers were statistically analysed through the ANOVA test (P>0.01).
      The Tukey test was used as a complementary tool to determine which treatment was
      different from the other treatments (P>0.05). The highest mortality was observed
      with P. laevigata hexanic extract from stem and leaves combined, which produced
      51%, 81% and 86% larval mortality at 24, 48 and 72 h post-exposure, respectively.
      On the other hand, B. copallifera stem acetonic extract exhibited 18%, 59% and
      66% nematicidal activity after 24, 48 and 72 h of exposure, respectively.

PMID- 18053305
TI  - Effects of green tea on insulin sensitivity, lipid profile and expression of
      PPARalpha and PPARgamma and their target genes in obese dogs.
AB  - As in man, canine obesity is associated with insulin resistance, dyslipidaemia
      and other chronic diseases. This study was designed to examine the effects of a
      nutritional supplement (green tea) on insulin sensitivity and plasma lipid
      concentrations in an obese insulin-resistant dog model. We also determined mRNA
      expression of two transcription factors, PPARgamma and PPARalpha, and some of
      their target genes, including GLUT4, lipoprotein lipase (LPL) and adiponectin.
      Obese dogs were divided into two groups: a green tea group (n 6); a control group
      (n 4). Dogs in the green tea group were given green tea extract (80 mg/kg per d)
      orally, just before their single daily meal, for 12 weeks. Insulin sensitivity
      (using a euglycaemic-hyperinsulinaemic clamp) and concentrations of plasma TAG,
      total cholesterol and NEFA were assessed in each group. Gene expression was
      measured in visceral and subcutaneous adipose tissues and in liver and skeletal
      muscle, by real-time PCR. At 12 weeks in the green tea group, mean insulin
      sensitivity index was 60 (SEM 11) % higher (P < 0.05) and TAG concentration 50
      (SEM 10) % lower (P < 0.001), than baseline. PPARgamma, GLUT4, LPL and
      adiponectin expression were significantly higher in both adipose tissues, whilst
      PPARalpha and LPL expression were significantly higher in skeletal muscle,
      compared with baseline. These findings show that nutritional doses of green tea
      extract may improve insulin sensitivity and lipid profile and alter the
      expression of genes involved in glucose and lipid homeostasis.

PMID- 18053306
TI  - The effect of a dietary supplement of potassium chloride or potassium citrate on
      blood pressure in predominantly normotensive volunteers.
AB  - Blood pressure (BP) shows a continuous relationship with the risk of CVD. There
      is substantial evidence that dietary potassium exerts an anti-pressor effect.
      Most clinical trials have used KCl. However, the chloride ion may have a pressor
      effect and in foods potassium is associated with organic anions. In a double
      blind randomized placebo-controlled trial we explored the effect on BP of two
      salts of potassium, KCl and potassium citrate (K-cit), in predominantly young
      healthy normotensive volunteers. The primary outcome was the change in mean
      arterial pressure as measured in a clinic setting. After 6 weeks of
      supplementation, compared with the placebo group (n 31), 30 mmol K-cit/d (n 28)
      changed mean arterial pressure by -5.22 mmHg (95% CI -8.85, -4.53) which did not
      differ significantly from that induced by KCl (n 26), -4.70 mmHg (-6.56, -2.84).
      The changes in systolic and diastolic BP were -6.69 (95% CI -8.85, -4.43) and 
      4.26 (95% CI -6.31, -2.21) mmHg with K-cit and -5.24 (95% CI -7.43, -3.06) and 
      4.30 (95% CI -6.39, -2.20) mmHg with KCl, and did not differ significantly
      between the two treatments. Changes in BP were not related to baseline urinary
      electrolytes. A greater treatment-related effect was observed in those with
      higher systolic BP. Increasing dietary potassium could therefore have a
      significant impact on the progressive rise in BP in the entire population.

PMID- 18053307
TI  - Response of cell cycle/stress-related protein expression and DNA damage upon
      treatment of CaCo2 cells with anthocyanins.
AB  - Anthocyanins are a class of flavonoids, widely spread throughout the plant
      kingdom, exhibiting important antioxidant and anti-inflammatory actions as well
      as chemotherapeutic effects; nonetheless, little is known about the molecular
      mechanisms by which these activities are exerted. The present study is aimed at
      investigating molecular mechanisms involved in the chemotherapeutic effects
      induced by both cyanidin-3-O-beta glucopyranoside (CY3G) and its aglycon form,
      cyanidin chloride (CY), in human colon cancer cells (CaCo2). The effect on cell
      growth, reactive oxygen species (ROS) formation and cell cycle/stress proteins
      modification, including ataxia teleangectasia mutated protein (ATM), p53, p21, 8
      oxoguanine DNA glycosylase (OGG1), 70 kDa heat shock protein (HSP70) and
      topoisomerase IIbeta, as well as on DNA fragmentation, was determined. CY and
      CY3G treatment affect cell growth and cell proliferation, this latter in a
      moderately dose-dependent way. Interestingly, ROS level is decreased by any
      concentration of CY and, only at the lowest concentration, by CY3G. Moreover, the
      two molecules exert their activities increasing ATM, topoisomerase II, HSP70 and
      p53 expression. The analysis of DNA fragmentation by Comet assay evidences: (1) a
      dose-dependent increase in DNA damage only after treatment with CY3G; (2) a more
      evident trend in the DNA fragmentation when the treatment is performed on agarose
      embedded cells (cellular atypical Comet); (3) a highly dose-dependent DNA
      fragmentation induced by CY when the treatment is carried out on agarose embedded
      naked DNA (acellular atypical Comet). The present findings substantiate a
      possible chemotherapeutic role of anthocyanins and suggest that CY and CY3G act
      on CaCo2 by different mechanisms, respectively, ROS-dependent and ROS
      independent.

PMID- 18053308
TI  - Effect of Ramadan fasting on some indices of insulin resistance and components of
      the metabolic syndrome in healthy male adults.
AB  - The purpose of the present study was to evaluate the effect of Ramadan fasting on
      insulin sensitivity in subjects with the metabolic syndrome. Males (n 55; age
      34.1 (sd 8.9) years) with the metabolic syndrome were studied. Blood pressure,
      waist circumference, body weight, HDL-cholesterol (HDL-C), TAG, fasting plasma
      glucose (FPG), fasting blood insulin and insulin resistance indices (quantitative
      insulin sensitivity check index (QUICKI), homeostasis model assessment of insulin
      resistance (HOMA-IR) and reciprocal index of HOMA-IR (1/HOMA-IR)) were evaluated
      before and after 30 d of Ramadan fasting (two meals at 12 h intervals). The
      dietary intake was estimated by 24 h recall before and after fasting. The total
      daily energy intake was decreased by 234.6 (sd 88.2) kJ/d in the fasting period
      (P = 0.005). 1/HOMA-IR, QUICKI and HDL-C were significantly increased (P = 0.005,
      P = 0.001 and P = 0.004) and FPG significantly decreased (P < 0.005) after
      fasting. Simple linear regression analysis demonstrated that HOMA-IR, 1/HOMA-IR
      and QUICKI were related to waist circumference after intervention (r 0.458, P <
      0.001; r - 0.396, P < 0.05; r - 0.342, P < 0.05). In conclusion, the present
      study showed that the combined change in the number and timing of meals and
      portioning of the entire intake into only two meals per d may increase insulin
      sensitivity in subjects with the metabolic syndrome even when the decrease in
      energy consumption is minimal.

PMID- 18053309
TI  - Population-specific Mini Nutritional Assessment effectively predicts the
      nutritional state and follow-up mortality of institutionalized elderly Taiwanese
      regardless of cognitive status.
AB  - The study was conducted to determine the effectiveness of a modified Mini
      Nutritional Assessment (MNA) for assessing the nutritional status and predicting
      follow-up mortality of institutionalized elderly Taiwanese. The study was
      conducted in a large long-term care centre in central Taiwan. Trained
      interviewers assisted by the caregivers elicited sociodemographic data,
      healthcare and disease history, and answers to the MNA screen from each subject.
      One researcher performed all subjects' anthropometric measurements. Plasma
      albumin and cholesterol concentrations were determined. Results showed that the
      MNA without BMI, modified according to population-specific mid-arm circumference
      and calf circumference cut-points, effectively predicted the nutritional risk
      status of the elderly regardless of cognitive status. Substituting caregiver's
      assessments for self-viewed nutrition and health status (questions O and P of
      MNA) improved the predicting power of the tool in cognition-normal subjects.
      Results showed that 21.9% of the elderly were malnourished, 59.2% were at risk of
      malnutrition and 18.9% were normal according to self-assessment whereas 14.2%
      were malnourished, 59.2% were at risk of malnutrition, and 26.6% were normal
      according to caregiver's evaluation. The tool was also effective in predicting 12
      and 6-month follow-up mortality in cognition-normal and cognition-impaired
      elderly, respectively. Results indicate that a population-specific MNA can
      effectively predict the nutritional status and 6-month follow-up mortality of
      elderly Taiwanese regardless of cognitive condition. Easier and wider application
      of the tool will enable early detection of emerging nutritional problems and
      timely intervention to prevent the development of severe malnutrition in the
      elderly.

PMID- 18053310
TI  - Dietary flaxseed lignan extract lowers plasma cholesterol and glucose
      concentrations in hypercholesterolaemic subjects.
AB  - Lignans, derived from flaxseed, are phyto-oestrogens being increasingly studied
      for their health benefits. An 8-week, randomised, double-blind, placebo
      controlled study was conducted in fifty-five hypercholesterolaemic subjects,
      using treatments of 0 (placebo), 300 or 600 mg/d of dietary secoisolariciresinol
      diglucoside (SDG) from flaxseed extract to determine the effect on plasma lipids
      and fasting glucose levels. Significant treatment effects were achieved (P < 0.05
      to < 0.001) for the decrease of total cholesterol (TC), LDL-cholesterol (LDL-C)
      and glucose concentrations, as well as their percentage decrease from baseline.
      At weeks 6 and 8 in the 600 mg SDG group, the decreases of TC and LDL-C
      concentrations were in the range from 22.0 to 24.38 % respectively (all P < 0.005
      compared with placebo). For the 300 mg SDG group, only significant differences
      from baseline were observed for decreases of TC and LDL-C. A substantial effect
      on lowering concentrations of fasting plasma glucose was also noted in the 600 mg
      SDG group at weeks 6 and 8, especially in the subjects with baseline glucose
      concentrations > or = 5.83 mmol/l (lowered 25.56 and 24.96 %; P = 0.015 and P =
      0.012 compared with placebo, respectively). Plasma concentrations of
      secoisolariciresinol (SECO), enterodiol (ED) and enterolactone were all
      significantly raised in the groups supplemented with flaxseed lignan. The
      observed cholesterol-lowering values were correlated with the concentrations of
      plasma SECO and ED (r 0.128-0.302; P < 0.05 to < 0.001). In conclusion, dietary
      flaxseed lignan extract decreased plasma cholesterol and glucose concentrations
      in a dose-dependent manner.

PMID- 18053311
TI  - Acute effects on metabolism and appetite profile of one meal difference in the
      lower range of meal frequency.
AB  - A gorging pattern of food intake has been shown to enhance lipogenesis and
      increase body weight, which may be due to large fluctuations in storage and
      mobilisation of nutrients. In a state of energy balance, increasing meal
      frequency, and thereby decreasing inter-meal interval, may prevent large
      metabolic fluctuations. Our aim was to study the effect of the inter-meal
      interval by dividing energy intake over two or three meals on energy expenditure,
      substrate oxidation and 24 h satiety, in healthy, normal-weight women in a state
      of energy balance. The study was a randomised crossover design with two
      experimental conditions. During the two experimental conditions subjects
      (fourteen normal-weight women, aged 24.4 (SD 7.1) years, underwent 36 h sessions
      in energy balance in a respiration chamber for measurements of energy expenditure
      and substrate oxidation. The subjects were given two (breakfast, dinner) or three
      (breakfast, lunch, dinner) meals per d. We chose to omit lunch in the two meals
      condition, because this resulted in a marked difference in inter-meal-interval
      after breakfast (8.5 h v. 4 h). Eating three meals compared with two meals had no
      effects on 24 h energy expenditure, diet-induced thermogenesis, activity-induced
      energy expenditure and sleeping metabolic rate. Eating three meals compared with
      two meals increased 24 h fat oxidation, but decreased the amount of fat oxidised
      from the breakfast. The same amount of energy divided over three meals compared
      with over two meals increased satiety feelings over 24 h. In healthy, normal
      weight women, decreasing the inter-meal interval sustains satiety, particularly
      during the day, and sustains fat oxidation, particularly during the night.

PMID- 18053312
TI  - Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of
      folate and related B vitamins and colorectal cancer: a case-control study in a
      population with relatively low folate intake.
AB  - Folate is key in one-carbon metabolism, disruption of which can interfere with
      DNA synthesis, repair, and methylation. Efficient one-carbon metabolism requires
      other B vitamins and the optimal activity of enzymes including 5,10
      methylenetetrahydrofolate reductase (MTHFR). We report a population-based case
      control study of folate intake, related dietary factors and MTHFR polymorphisms
      (C677T, A1298C) and colorectal cancer in a population with relatively high
      colorectal cancer incidence and relatively low folate intake. A total of 264
      cases with histologically confirmed incident colorectal cancer and 408 controls
      participated. There was no clear trend in risk with reported intakes of total, or
      dietary, folate, riboflavin, vitamin B12 or vitamin B6, nor were there
      interactions between folate intake and the other B vitamins or alcohol. For
      C677T, risk decreased with increasing variant alleles (multivariate OR for CT v.
      CC = 0.77 (95 % CI 0.52, 1.16); OR for TT v. CC = 0.62 (95 % CI 0.31, 1.24)),
      which, although not statistically significant, was consistent with previous
      studies. For A1298C, compared with AA subjects, CC subjects had modest, non
      significant, reduced risk (multivariate OR = 0.81 (95 % CI 0.45, 1.49)). There
      were significant interactions between total folate and C677T (P = 0.029) and
      A1298C (P = 0.025), and total vitamin B6 and both polymorphisms (C677T, P =
      0.016; A1298C, P = 0.033), although the patterns observed differed from previous
      studies. Seen against the setting of low folate intake, the results suggest that
      the role of folate metabolism in colorectal cancer aetiology may be more complex
      than previously thought. Investigation of particular folate vitamers (for
      example, tetrahydrofolate, 5,10-methylenetetrahydrofolate) may help clarify
      carcinogenesis pathways.

PMID- 18053313
TI  - Assessment of nutrient and water intake among adolescents from sports federations
      in the Federal District, Brazil.
AB  - Adolescents aged 11-14 years (n 326), belonging to organized sports federations
      in the Federal District, Brazil were interviewed. Subjects (n 107) provided four
      non-consecutive days of food consumption and 219 subjects provided two non
      consecutive days of intake. The objective was to assess their nutrient and water
      intake according to dietary reference intake values and their energy and
      macronutrient intake by sex and sports groups they were engaged in: endurance,
      strength-skill or mixed, according to the guidelines established by the American
      College of Sport Medicine (ACSM). Dietary data were corrected for intra
      individual variation. Total energy expenditure was higher among endurance
      athletes (P < 0.001) following their higher training time (P < 0.001) when
      compared to adolescents engaged in strength-skill or mixed sports. Total energy
      intake was only significantly higher among endurance-engaged females (P = 0.05).
      Protein intake of males was above the guidelines established by the ACSM for all
      sports groups. All male sport groups fulfilled the intake levels of carbohydrate
      per kg body weight but only females engaged in endurance sports fulfilled
      carbohydrate guidelines. Intakes of micronutrients with low prevalence of
      adequate intake were: vitamins B1, E and folate, magnesium and phosphorus. Few
      adolescents ( < 5 %) presented adequate intake for calcium, fibre, drinking water
      and beverages. For micronutrients, prevalence of adequacies were lower for
      females than males, except for liquids and water. Nutrition guidance is needed to
      help adolescents fulfil specific guidelines of macronutrient intake for their
      sports and to improve their intake of micronutrients and water. Special attention
      should be given to female adolescent athletes.

PMID- 18053314
TI  - The prevalence of postoperative pain in a sample of 1490 surgical inpatients.
AB  - BACKGROUND AND OBJECTIVE: To measure the prevalence of postoperative pain, an
      assessment was made of 1490 surgical inpatients who were receiving postoperative
      pain treatment according to an acute pain protocol. METHODS: Measurements of pain
      (scores from 0 to 100 on a visual analogue scale) were obtained three times a day
      on the day before surgery and on days 0-4 postoperatively; mean pain intensity
      scores were calculated. Patients were classified as having no pain (score 0-5),
      mild pain (score 6-40), moderate pain (score 41-74) or severe pain (score 75
      100). RESULTS: Moderate or severe pain was reported by 41% of the patients on day
      0, 30% on days 1 and 19%, 16% and 14% on days 2, 3 and 4. The prevalence of
      moderate or severe pain in the abdominal surgery group was high on postoperative
      days 0-1 (30-55%). A high prevalence of moderate or severe pain was found during
      the whole of days 1-4 in the extremity surgery group (20-71%) and in the
      back/spinal surgery group (30-64%). CONCLUSION: We conclude that despite an acute
      pain protocol, postoperative pain treatment was unsatisfactory, especially after
      intermediate and major surgical procedures on an extremity or on the spine.

PMID- 18053315
TI  - Substance P is involved in the cutaneous blood flow increase response to
      sympathetic nerve stimulation in persistently inflamed rats.
AB  - Changed vascular functions have been reported in several pathological conditions,
      such as chronic regional pain syndrome, obstructive vascular disease, and
      inflammation. Our previous experiments also showed that electrical stimulation of
      the lumbar sympathetic trunk (sympathetic stimulation: SS), which normally
      induces a decrease in blood flow (BF), caused a BF increase in about half of the
      measured sites in rats persistently inflamed with complete Freund's Adjuvant (AI
      rats). We also showed that the BF-increase response was only partially suppressed
      by the alpha1 antagonist at a higher dosage, suggesting the involvement of
      nonadrenergic mechanisms. We hypothesize that nonadrenergic mechanisms mediating
      vasodilatation might involve a vasodilating neuropeptide such as substance P (SP)
      that is released from sympathetic nerve terminals. In this experiment, we
      conducted an examination using an NK-1 receptor antagonist to determine whether
      SP plays any role in changed response to SS in AI rats, and also an
      immunohistochemical examination of whether SP is expressed in the lumbar
      sympathetic nerve ganglia (SG) of AI rats. The administration of an NK-1 receptor
      antagonist, CP-96,345, significantly reduced the BF-increase response to SS in AI
      rats, but its inactive enantiomer, CP-96,344, had no effect. Immunohistochemistry
      for SP revealed that SP-ir positive SG neurons (mean 13 neurons/rat) were found
      in 5 of 8 AI rats, whereas only one neuron was stained in 8 control rats. These
      results suggest that NK-1 receptor activation is involved in the BF-increase
      response to SS, and that this activation is in part mediated by SP from lumbar SG
      that was synthesized de novo in inflamed animals.

PMID- 18053317
TI  - Effects of ezetimibe, simvastatin, atorvastatin, and ezetimibe-statin therapies
      on non-cholesterol sterols in patients with primary hypercholesterolemia.
AB  - BACKGROUND: Levels of cholesterol are regulated by its synthesis, absorption, and
      elimination. Plasma levels of phytosterols (e.g., sitosterol, campesterol) and
      ratios of these sterols to total cholesterol (TC) are reported to correlate with
      efficiency of intestinal cholesterol absorption, whereas levels of certain
      cholesterol precursor sterols (e.g., desmosterol, lathosterol) and their ratios
      to TC correlate with cholesterol biosynthesis. However, there is a paucity of
      published data concerning the effects of combined treatment using HMG-CoA
      reductase inhibitors (statins) and a cholesterol absorption inhibitor (ezetimibe)
      on these parameters. OBJECTIVES: To characterize the effects of ezetimibe co
      administered with statins, compared with each treatment alone, on cholesterol
      precursor sterols and plasma phytosterol levels. METHODS: A post-hoc analysis was
      performed to determine the effects of treatment with ezetimibe 10 mg, simvastatin
      (10-80 mg), and atorvastatin (10-80 mg), alone or in combination, on these non
      cholesterol sterols using plasma samples from two randomized controlled trials
      involving patients with primary hypercholesterolemia (low-density lipo protein
      [LDL-C] = 145-250 mg/dL; triglycerides < or = 350 mg/dL; N = 975) but without a
      recent (< or = 6-month) history of coronary heart disease (CHD) or either
      uncontrolled or newly diagnosed diabetes mellitus. RESULTS: Ezetimibe monotherapy
      significantly reduced plasma sitosterol and campesterol concentrations from
      baseline compared with placebo (both p < 0.001), whereas statins significantly
      lowered desmo sterol and lathosterol levels (p < 0.001 vs. placebo). Co
      administration of ezetimibe and statins significantly decreased plasma levels of
      all of these sterols (p < 0.001). CONCLUSIONS: The observed effects of co
      administration of ezetimibe and statins on non-cholesterol sterols are consistent
      with net inhibition of sterol absorption (driven by ezetimibe) in conjunction
      with net inhibition of cholesterol synthesis (driven by statins). The potential
      influence of treatment-induced changes in phytosterols on cardiovascular risk
      warrants further investigation in long-term, prospective, randomized controlled
      trials. This post-hoc study was by nature exploratory, and, because data from
      such analyses are not customarily adjusted for multiple comparisons, some
      associations may have emerged as statistically significant by chance. Future
      prospective randomized controlled studies may help to confirm our findings and
      address other research issues, such as the generalizability of our findings to
      patients with CHD or diabetes mellitus and possible dose:response relationships
      between escalating statin (or ezetimibe-statin) doses and circulating non
      cholesterol levels.

PMID- 18053318
TI  - Clopidogrel versus aspirin in patients with atherothrombosis: CAPRIE-based
      calculation of cost-effectiveness for Germany.
AB  - OBJECTIVES: To model the 2-year cost-effectiveness of secondary prevention with
      clopidogrel versus aspirin (acetylsalicylic acid) (ASS) in German patients with
      myocardial infarction (MI), ischaemic stroke (IS) or diagnosed with peripheral
      arterial disease (PAD), based on CAPRIE trial data and from the perspective of
      German third party payers (TPP). METHODS: An existing Markov model was adapted to
      Germany by using German cost data. The model was extended by using different
      datasets for cardiovascular event survival times (Framingham vs. Saskatchewan
      health databases) and in two separate scenarios. RESULTS: The treatment with
      clopidogrel leads to a reduction of 13.19 vascular events per 1000 patients, of
      which 2.21 are vascular deaths. The overall incremental costs for the 2-year
      management of atherothrombotic patients with clopidogrel instead of ASS are
      calculated to be about euro1 241 440 per 1000 patients. The number of life-years
      saved (LYS) has been calculated as the difference in the number of life-years
      lost due to vascular death or events with ASS versus clopidogrel: it is 86.35 LYS
      when analysis is based on Framingham data and 66.07 LYS with Saskatchewan-based
      survival data. The incremental costs per LYS are euro14 380 and euro18 790,
      respectively. Cost-effectiveness is sensitive to changes in survival data,
      discounting and daily costs of clopidogrel, but stable against substantial (+/-
      25%) changes in all other cost data. CONCLUSION: The findings for Germany are in
      line with published results for Belgium (euro13 390 per LYS) and also with
      results for Italy (euro17 500 per LYS), both based on Saskatchewan data, and with
      a French analysis based on Framingham data (euro15 907 per LYS). Even if no
      officially accepted cost-effectiveness threshold exists for Germany at present,
      incremental cost-effectiveness results of less than euro20 000 per LYS for the
      treatment with clopidogrel can be assumed to be acceptable for German third party
      payers.

PMID- 18053319
TI  - Comparison of costs of sublingual immunotherapy and drug treatment in grass
      pollen induced allergy: results from the SIMAP database study.
AB  - OBJECTIVES: This analysis is focused on the comparison of costs of allergic
      rhinitis (R) alone or with allergic asthma (R + A) in grass pollen allergy, for
      subjects treated with sublingual immunotherapy (SLIT) and symptomatic drugs,
      versus standard care controls. METHODS: The SIMAP (Sublingual IMmunotherapy in
      Allergic Patients) study is a longitudinal observational database operated by a
      network of Allergy centers. Patients suffering from grass pollen allergy were
      included in this analysis and assigned to SLIT (plus drugs as needed) or to
      treatment with drugs alone. Outcome measures included use of medications, SLIT,
      visits and tests. Costs were assessed from the perspective of the Italian
      National Health Service; unit costs were obtained from published sources to
      produce an average cost/patient for the first year after enrolment. RESULTS: One
      hundred and two patients were analyzed. Demographics were comparable in the two
      groups. Overall per patient yearly cost of treatment was higher in SLIT patients,
      both in the whole sample (euro311 vs. euro180/patient), in the R (euro288 vs.
      euro116) and R + A (euro362 vs. euro230) subpopulations, with R + A patients
      generating more costs than R patients in both groups. Nevertheless considerable
      savings were obtained in the cost of symptomatic drugs (-22% for R; -34% for R +
      A) in SLIT patients. CONCLUSIONS: Other studies have shown that SLIT can reduce
      the use of drugs for asthma and rhinitis, but this is the first time this outcome
      has been demonstrated in a routine care population (in the medical practice
      environment of an observational study) within the first year of treatment.

PMID- 18053320
TI  - Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic
      biomarkers in patients with type 2 diabetes treated for at least 3 years.
AB  - BACKGROUND: Exenatide, an incretin mimetic for adjunctive treatment of type 2
      diabetes (T2DM), reduced hemoglobin A(1c) (A1C) and weight in clinical trials.
      The objective of this study was to evaluate the effects of > or = 3 years
      exenatide therapy on glycemic control, body weight, cardiometabolic markers, and
      safety. METHODS: Patients from three placebo-controlled trials and their open
      label extensions were enrolled into one open-ended, open-label clinical trial.
      Patients were randomized to twice daily (BID) placebo, 5 mug exenatide, or 10 mug
      exenatide for 30 weeks, followed by 5 mug exenatide BID for 4 weeks, then 10 mug
      exenatide BID for > or = 3 years of exenatide exposure. Patients continued
      metformin and/or sulfonylureas. RESULTS: 217 patients (64% male, age 58 +/- 10
      years, weight 99 +/- 18 kg, BMI 34 +/- 5 kg/m(2), A1C 8.2 +/- 1.0% [mean +/- SD])
      completed 3 years of exenatide exposure. Reductions in A1C from baseline to week
      12 (-1.1 +/- 0.1% [mean +/- SEM]) were sustained to 3 years (-1.0 +/- 0.1%; p <
      0.0001), with 46% achieving A1C < or = 7%. Exenatide progressively reduced body
      weight from baseline (-5.3 +/- 0.4 kg at 3 years; p < 0.0001). Patients with
      elevated serum alanine aminotransferase (ALT) at baseline (n = 116) had reduced
      ALT (-10.4 +/- 1.5 IU/L; p < 0.0001) and 41% achieved normal ALT. Patients with
      elevated ALT at baseline tended to lose more weight than patients with normal ALT
      at baseline (-6.1 +/- 0.6 kg vs. -4.4 +/- 0.5 kg; p = 0.03), however weight
      change was minimally correlated with baseline ALT (r = -0.01) or ALT change (r =
      0.31). Homeostasis Model Assessment B (HOMA-B), blood pressure, and aspartate
      aminotransferase (AST) all improved. A subset achieved 3.5 years of exenatide
      exposure and had serum lipids available for analysis (n = 151). Triglycerides
      decreased 12% (p = 0.0003), total cholesterol decreased 5% (p = 0.0007), LDL-C
      decreased 6% (p < 0.0001), and HDL-C increased 24% (p < 0.0001). Exenatide was
      generally well tolerated. The most frequent adverse event was mild-to-moderate
      nausea. The main limitation of this study is the open-label, uncontrolled nature
      of the study design which does not provide a placebo group for comparison.
      CONCLUSION: Adjunctive exenatide treatment for > or = 3 years in T2DM patients
      resulted in sustained improvements in glycemic control, cardiovascular risk
      factors, and hepatic biomarkers, coupled with progressive weight reduction.

PMID- 18053321
TI  - Review of the ethnobotany, chemistry, biological activity and safety of the
      botanical dietary supplement Morinda citrifolia (noni).
AB  - Morinda citrifolia, commonly called noni, has a long history as a medicinal plant
      and its use as a botanical dietary supplement has grown tremendously in recent
      years. This has prompted a concomitant increase in research on the phytochemical
      constituents and biological activity of noni. A relatively large number of
      scientific publications on noni have been published in recent years, including a
      number of review articles. The goals of this review are to provide an updated
      categorization of the phytochemical constituents found in noni and to provide
      perspective for its extensive utilization as a major botanical dietary
      supplement. Included herein are a comprehensive list of known ethnobotanical uses
      and common names of M. citrifolia, a brief summary of relevant biological studies
      and a discussion of the safety of noni as a supplement.

PMID- 18053322
TI  - Preparation and characterization of quercetin-loaded polymethyl methacrylate
      microcapsules using a polyol-in-oil-in-polyol emulsion solvent evaporation
      method.
AB  - Flavonoids and related compounds exhibit a wide range of useful pharmacological
      properties but present challenges related to their stability and solubility in
      commonly available solvents. In this study, polymethyl methacrylate (PMMA)
      microcapsules were prepared using a novel polyol-in-oil-in-polyol (P/O/P)
      emulsion solvent evaporation method as a means of stabilizing the flavonoids,
      using quercetin as a model flavonoid drug. The morphology of the microcapsules
      was evaluated using a scanning electron microscope, revealing a spherical shape
      with a smooth surface. The cross-section image of the PMMA microcapsules prepared
      with an amphiphilic polymer in the inner polyol phase showed that the
      microcapsule was filled with several submicron microspheres. The mean diameter
      varied from 1.03+/-0.12 microm to 2.39+/-0.42 microm, and the encapsulation
      efficiency ranged from 12.7% to 26.9%. When free quercetin was stored at 42
      degrees C, the residual quercetin content gradually decreased to 18% over 28 days
      as a result of oxidation. However, when encapsulated in PMMA microcapsules with
      an amphiphilic polymer in the inner polyol phase, the residual quercetin content
      decreased to just 82%. In-vitro release studies indicated a sustained release
      pattern throughout the 36-h study. The release kinetics of the microcapsules with
      an amphiphilic polymer followed a diffusion-controlled mechanism and the
      microcapsule without amphiphilic polymer followed an anomalous diffusion
      behaviour. This study suggests that the novel P/O/P emulsion solvent evaporation
      method can be applied to the encapsulation of flavonoids.

PMID- 18053323
TI  - Influence of solid lipid microparticle carriers on skin penetration of the
      sunscreen agent, 4-methylbenzylidene camphor.
AB  - The objective of this study was to prepare lipid microparticles (LMs) loaded with
      the sunscreen agent, 4-methylbenzylidene camphor (4-MBC), to achieve decreased
      skin penetration of this UV filter. The microparticles were produced by the melt
      dispersion technique using tristearin as lipidic material and hydrogenated
      phosphatidylcholine as the surfactant. The obtained microparticles were
      characterized by scanning electron microscopy and differential scanning
      calorimetry. Release of 4-MBC from the LMs was found to be slower than its
      dissolution rate. The influence of the LMs' carrier system on percutaneous
      penetration was evaluated after their introduction in a model topical formulation
      (emulsion). In-vitro measurements were performed with cellulose acetate membranes
      in Franz diffusion cells. The 4-MBC release and diffusion was decreased by 66.7
      77.3% with the LM formulation, indicating that the retention capacity of the
      microparticles was maintained after incorporation into the emulsion. In-vivo
      human skin penetration of 4-MBC was investigated by tape stripping, a technique
      for selectively removing the upper cutaneous layers. The amount of sunscreen
      penetrating into the stratum corneum was greater for the emulsion containing non
      encapsulated 4-MBC (36.55% of the applied dose) compared with the formulation
      with the sunscreen-loaded microparticles (24.57% of the applied dose). The
      differences between the two formulations were statistically significant in the
      first (2-4) horny layer strips. Moreover, the LMs' effect measured in-vivo was
      less pronounced than in-vitro. The increased 4-MBC retention on the skin surface
      achieved by its incorporation in the LMs should enhance its efficacy and reduce
      the potential toxicological risk associated with skin penetration.

PMID- 18053325
TI  - Potentiating effect of beta-caryophyllene on anticancer activity of alpha
      humulene, isocaryophyllene and paclitaxel.
AB  - beta-caryophyllene is a sesquiterpene widely distributed in essential oils of
      various plants. Several biological activities are attributed to beta
      caryophyllene, such as anti-inflammatory, antibiotic, antioxidant,
      anticarcinogenic and local anaesthetic activities. In this work, the potentiating
      effect of beta-caryophyllene on the anticancer activity of alpha-humulene,
      isocaryophyllene and paclitaxel against MCF-7, DLD-1 and L-929 human tumour cell
      lines was evaluated. A non-cytotoxic concentration of beta-caryophyllene
      significantly increased the anticancer activity of alpha-humulene and
      isocaryophyllene on MCF-7 cells: alpha-humulene or isocaryophyllene alone (32
      microg mL(-1)) inhibited cell growth by about 50% and 69%, respectively, compared
      with 75% and 90% when combined with 10 microg mL(-1) beta-caryophyllene.
      Moreover, beta-caryophyllene potentiated the anticancer activity of paclitaxel on
      MCF-7, DLD-1 and L-929 cell lines. The highest potentiating effect was obtained
      in DLD-1 cells treated with paclitaxel combined with 10 microg mL(-1) beta
      caryophyllene, which increased the paclitaxel activity about 10-fold. The
      intracellular accumulation of paclitaxel-oregon green was evaluated in
      combination with concentrations of beta-caryophyllene ranging from 2.5 to 40
      microg mL(-1). beta-Caryophyllene (10 microg mL(-1)) significantly increased the
      intracellular accumulation of paclitaxel-oregon green (about 64% over controls).
      Moreover, beta-caryophyllene induced intracellular accumulation of calcein but
      not verapamil, an inhibitor of P-glycoprotein and multidrug resistance related
      protein transporters, suggesting that beta-caryophyllene promotes drug
      accumulation by a different mechanism of action. These results suggest that beta
      caryophyllene facilitates the passage of paclitaxel through the membrane and thus
      potentiates its anticancer activity.

PMID- 18053324
TI  - Cod liver oil supplementation improves cardiovascular and metabolic abnormalities
      in streptozotocin diabetic rats.
AB  - Abnormalities in the metabolism of essential fatty acids and the results of
      increased oxidative stress have been implicated in cardiovascular disorders
      observed in diabetes mellitus. This study, therefore, aimed to investigate the
      effects of cod liver oil (CLO, Lysi Ltd, Iceland), which comprises mainly an
      antioxidant vitamin A, n:3 polyunsaturated fatty acids (n:3 PUFAs),
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cardiovascular
      abnormalities in streptozotocin (STZ)-diabetic rats. Two days after single STZ
      (55 mg kg(-1), i.p.) or vehicle injection, diabetes was verified by increased
      blood glucose, and non-diabetic and diabetic rats were left untreated or treated
      with CLO (0.5 mL kg(-1) daily, by intragastric probing) for 12 weeks. Plasma
      glucose, triacylglycerol and cholesterol concentrations were significantly
      elevated in 12-week untreated-diabetic rats; CLO provided better weight gain,
      entirely prevented the plasma lipid abnormalities, but partially controlled the
      glycaemia in diabetic rats. In isolated aorta rings, diabetes resulted in
      increased phenylephrine-induced vasoconstriction and isoprenaline-induced
      vasorelaxation, impaired endothelium-dependent vasodilatation and unchanged
      responsiveness to sodium nitroprusside. CLO treatment completely prevented
      endothelial deficiency, partly corrected the phenylephrine-induced
      vasoconstriction and did not affect the responses to isoprenaline and sodium
      nitroprusside in diabetic aorta. Diabetes also produced a marked decrease in the
      rate of spontaneously beating right atria and a significant increase in basal
      contractile force of left ventricular papillary muscle. The responsiveness of
      right atria to the positive chronotropic effect of isoprenaline was significantly
      decreased in diabetic rats, and was increased in CLO-treated diabetic rats. The
      positive chronotropic effect of noradrenaline was markedly increased in diabetic
      atria, but prevented by CLO treatment. Diabetes also resulted in an increased
      positive inotropic response of papillary muscle to both noradrenaline and
      isoprenaline, which were prevented by CLO treatment. CLO treatment also resulted
      in lower tissue sensitivity (pD(2)) to these agonists in diabetic papillary
      muscle. Ventricular hydroxyproline content was found to be unchanged among the
      experimental groups. The ultrastructure of diabetic myocardium displayed various
      degenerations (i.e. intracellular oedema, myofibrillar fragmentation, condensed
      pleomorphic mitochondria, thick capillary irregular basement membrane, swollen
      endothelial cells), which were partially prevented by CLO treatment. We conclude
      that the supplementation with CLO is effective in preventing cardiovascular
      disorders observed in experimental diabetes.

PMID- 18053326
TI  - Substituted tetrahydroisoquinoline compound B3 inhibited P-glycoprotein-mediated
      multidrug resistance in-vitro and in-vivo.
AB  - P-glycoprotein (P-gp) mediated multidrug resistance (MDR) is one of the main
      obstacles in tumour chemotherapy. A promising approach to reverse MDR is the
      combined use of nontoxic and potent P-gp inhibitor with conventional anticancer
      drugs. We have examined the potential of a newly synthesized
      tetrahydroisoquinoline derivative B3 as a MDR-reversing agent. The MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to examine
      the effect of B3 on the cytotoxicity in K562/A02 and MCF-7/ADM cells caused by
      doxorubicin (adriamycin). Accumulation and efflux of P-gp substrate rhodamine123
      in K562/A02 and primary cultured rat brain microvessel endothelial cells (RBMECs)
      were measured to evaluate the inhibitory effect of B3 on P-gp. The K562/A02
      xenograft model in nude mice was established to examine MDR-reversing efficacy of
      B3 in-vivo. The results indicated that co-administration of B3 resulted in an
      increase on chemosensitivity of K562/A02 and MCF-7/ADM cells to doxorubicin in a
      dose-dependent manner. Rhodamine123 accumulation in K562/A02 cells and RBMECs
      were significantly enhanced after the incubation with various concentrations of
      B3. Furthermore, B3 inhibited the efflux of rhodamine123 from RBMECs. Co
      administration of B3 with doxorubicin significantly decreased weight and volume
      of tumour in nude mice. In conclusion, B3 is a novel and potent MDR reversal
      agent with the potential to be an adjunctive agent for tumour chemotherapy.

PMID- 18053327
TI  - Bicyclol, a synthetic dibenzocyclooctadiene derivative, decreases hepatic lipids
      but increases serum triglyceride level in normal and hypercholesterolaemic mice.
AB  - Bicyclol is used for the treatment of chronic hepatitis B in China. In this
      study, the effects of bicyclol (100 or 300 mg kg(-1), p.o.) on serum and liver
      lipid contents were investigated in both normal and experimentally induced
      hypercholesterolaemic mice. Hypercholesterolaemia was induced by either oral
      administration of cholesterol/bile salt or feeding a diet containing
      lard/cholesterol. Daily administration of bicyclol for 7 days dose-dependently
      increased the serum triglyceride level (29-80%) but slightly decreased the
      hepatic total cholesterol level (12-17%) in normal mice. Co-administration of
      bicyclol with cholesterol/bile salt decreased the hepatic triglyceride and total
      cholesterol levels (7-15% and 25-31%, respectively), when compared with the drug
      untreated and cholesterol/bile salt-treated group. Bicyclol treatment for 7 days
      decreased hepatic triglyceride (5-76%) and total cholesterol (5-48%) levels in
      mice fed with high-fat/cholesterol diet. In contrast, bicyclol treatment
      increased the serum triglyceride level (18-77%) in mice treated with
      cholesterol/bile salt or fed with high-fat/cholesterol diet. Bicyclol treatment
      also caused an increase in hepatic index of normal and hypercholesterolaemic mice
      (3-32%). The results indicate that bicyclol treatment can invariably decrease
      hepatic lipid levels and increase serum triglyceride levels in normal and
      hypercholesterolaemic mice.

PMID- 18053328
TI  - Coptidis Rhizoma attenuates repeated nicotine-induced behavioural sensitization
      in the rat.
AB  - Repeated injections of nicotine can produce an increase in locomotor activity and
      the expression of immediate-early gene, c-fos, in the central dopaminergic areas.
      Many studies have shown that Coptidis Rhizoma (CR) and its main alkaloid
      compound, berberine (BER), have a suppressive effect on the central nervous
      system. We examined the influence of CR or BER on repeated nicotine-induced
      locomotor activity in rats and the change of c-Fos expression in the brain by
      using immunohistochemistry. Male Sprague-Dawley rats were given CR and BER before
      repeated injections of nicotine hydrochloride (0.4 mg kg(-1), s.c.) twice daily
      for 7 days. After 3 days withdrawal, rats received a challenge injection of
      nicotine. Pretreatment with CR (100 mg kg(-1), i.p.) and BER (100 mg kg(-1),
      i.p.) significantly inhibited the nicotine-induced locomotor activity and
      expression of c-Fos in the striatum and the nucleus accumbens. These results
      suggest that CR and BER may produce inhibitory effects of nicotine on behavioural
      sensitization by possibly reducing postsynaptic neuronal activation in the
      central dopaminergic systems.

PMID- 18053329
TI  - Chemistry and biology of antioxidants.

PMID- 18053330
TI  - Antioxidant properties of phenols.
AB  - The current understanding of the antioxidant properties of phenols (in
      homogeneous solutions) is reviewed, with particular emphasis on the role of the
      solvent. Phenols (ArOH) are known to reduce the rates of oxidation of organic
      matter by transferring a H atom (from their OH groups) to the chain-carrying ROO*
      radicals, a mechanism that most likely involves a concerted transfer of the
      hydrogen as a proton and of one electron between the two oxygen atoms, O-H---O*
      (proton-coupled electron transfer mechanism). The antioxidant capabilities of
      phenols are strongly reduced by hydrogen-bond accepting solvents since the
      hydrogen-bonded molecules ArOH---S are virtually unreactive toward ROO* radicals.
      The magnitude of these kinetic solvent effects is determined by the solute
      acidity alpha(2)(H) of ArOH (range 0 to 1) and solvent basicity beta(2)(H) (range
      0 to 1). Hydroxyl solvents (alcohols) have a double effect on ArOH. On the one
      hand, they act as hydrogen-bond accepting solvents and reduce the conventional
      rates of the ArOH + ROO* reaction. On the other hand, these solvents favour the
      ionization of ArOH into their phenoxide anions ArO(-), which may react with ROO*
      very rapidly by electron transfer (sequential proton loss electron transfer
      mechanism). The overall effect is therefore determined by the ionization degree
      of ArOH. Other aspects of the kinetics and thermodynamics of ArOH + ROO* are also
      discussed.

PMID- 18053331
TI  - Peroxynitrite and nitrosoperoxycarbonate, a tightly connected oxidizing-nitrating
      couple in the reactive nitrogen-oxygen species family: new perspectives for
      protection from radical-promoted injury by flavonoids.
AB  - Peroxynitrite is the product of the reaction of nitric oxide with superoxide
      radical and is implicated in the pathogenesis of a wide variety of human
      diseases, being responsible for in-vivo oxidation/nitration events.
      Nitrosoperoxycarbonate anion, formed by the interaction of peroxynitrite with
      CO(2)/bicarbonate at physiological concentrations, provides a new interpretation
      of oxidative/nitrative processes formerly attributed to peroxynitrite. The aim of
      this review is to summarize the chemistry and biology of peroxynitrite and
      radical species related to nitrosoperoxycarbonate anion, as well as the
      information available regarding the molecular mechanisms that determine and
      regulate radical-promoted injury by the two tightly connected species at
      physiological concentrations. Interception of carbonate and nitro radicals
      produced by interaction of peroxynitrite with CO(2)/bicarbonate, as in-vivo
      prevention of pathological events, creates new perspectives for the evaluation of
      safe scavengers of oxidative/nitrative stress at the physiological level. In this
      respect, natural products such as flavonoids hold a preeminent position among the
      vast array of compounds endowed with such properties.

PMID- 18053332
TI  - Efficient synthesis of polyoxygenated flavones from naturally occurring
      flavanones.
AB  - Flavonoids are constituents of the human diet (they are present in many beverages
      and food), and in organisms they are responsible for several biological
      functions, including that of antioxidant. Because of the increasing interest in
      these molecules, methods for their synthesis and structural modification are of
      great importance; studies on the biological activities of many of these compounds
      are insufficient because of their scarcity and/or high cost. We have developed an
      expeditious synthesis of polyoxygenated flavones, starting from available and
      inexpensive flavanones, using a bromination-methoxylation procedure. A series of
      flavonoids that are not otherwise accessible can be prepared using this method.
      As an example, 3'-demethoxysudachitin, a limited flavone possessing antimicrobial
      activity against methicillin-resistant Staphylococcus aureus and Helicobacter
      pylori and acting as a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenger, was
      prepared in fairly satisfactory yield.

PMID- 18053333
TI  - Radical-scavenging polyphenols: new strategies for their synthesis.
AB  - New strategies for the synthesis of polyphenols, compounds with antioxidant
      properties contained in every kind of plants, are discussed. Syntheses of
      different classes of polyphenols, namely ubiquinones, present in many natural
      systems in which electron-transfer mechanisms are involved, hydroxytyrosol, one
      of the main components of the phenol fraction in olives, and flavonoids,
      widespread in the plant kingdom, were approached by simple and environmentally
      sustainable methods.

PMID- 18053334
TI  - Involvement of plasma membrane redox systems in hormone action.
AB  - Reactive oxygen species (ROS) is the common name used to describe the partially
      reduced forms of molecular oxygen that may be generated in cells during oxidative
      metabolism. They are normally considered to be toxic, and cells possess various
      defence systems to protect themselves including antioxidant enzymes and low
      molecular weight antioxidants like vitamin C and vitamin E. However, it is now
      clear that small amounts of ROS also act as messenger molecules in cell signal
      transduction pathways; the plasma membrane of eukaryotic cells in particular
      contains a variety of different ROS-producing oxidases and reductases, of which
      the best characterized are the superoxide-producing NADPH oxidases. It has been
      known for many years that membrane redox activity can be changed rapidly by
      various hormones and growth factors, but the molecular mechanisms involved and
      the physiological importance of this phenomenon have only recently begun to be
      unveiled. This review summarizes the state of the art on plasma membrane-based
      ROS signalling in the pathways of insulin, steroid and thyroid hormones and
      growth factors. The apparent paradox of ROS being essential biomolecules in the
      regulation of cellular functions, but also toxic by-products of metabolism, may
      be important for the pharmacological application of natural and synthetic
      antioxidants.

PMID- 18053336
TI  - Protective effect of icariin on DNA against radical-induced oxidative damage.
AB  - Icariin (2-(4'-methoxylphenyl)-3-rhamnosido-5-hydroxyl-7-glucosido-8-(3'-methyl-2
      butylenyl)-4-chromanone) is a flavonoid with a rhamnose as ligand. It is the
      major component in Herba epimedii, widely used for the treatment of
      atherosclerosis and neuropathy in Chinese traditional medicine, and its
      antioxidative property has attracted much scientific interest. The major
      objective of this work is to determine the antioxidative effect of icariin
      against oxidative DNA damage induced by 2,2'-azobis(2-amidinopropane)
      dihydrochloride (AAPH). The oxidative damage of DNA was followed by measuring the
      formation of carbonyl compounds that can react with thiobarbituric acid (TBA) to
      form thiobarbituric acid reactive substance (TBARS). We found that icariin
      protects DNA against AAPH-induced oxidative damage in a concentration-dependent
      manner, although it does not affect the rate of AAPH-induced DNA damage. This
      result indicates that icariin is a concentration-dependent chemopreventor in
      protecting DNA against radical-induced damage.

PMID- 18053335
TI  - Antioxidant activity of 4-methylcoumarins.
AB  - Polyphenolic coumarins are known to act as antioxidants in biological systems,
      but it is difficult to distinguish their antioxidant activity from the many other
      effects they produce in cells. We have determined the radical scavenging capacity
      of 22 structurally related natural and synthetic 4-methylcoumarins, by measuring
      their reaction with radicals, galvinoxyl and 2,2-diphenyl-1-picrylhydrazyl, using
      electron paramagnetic resonance spectroscopy. Efficient antioxidant activity of 4
      methylcoumarins in cells was verified using the DCF fluorescent probe assay for
      determination of intracellular reactive oxygen species levels. As expected, the o
      dihydroxysubstituted coumarins were found to be excellent radical scavengers and
      better than the m-dihydroxysubstituted or monohydroxysubstituted analogues, but
      surprisingly the corresponding o-diacetoxy derivatives also turned out to be good
      scavengers, even in the absence of an esterase. Another unexpected result was
      that the antioxidant efficiency of 4-methylcoumarins could be modulated by
      introducing an ethoxycarbonylethyl substituent at the C-3 position; this effect
      cannot be explained by simple electron donating/withdrawing properties. Coumarin
      concentrations of 10 microM or less were used in all experiments, corresponding
      to the levels relevant for therapeutic purposes. Considering that 4
      methylcoumarins, in contrast to many other coumarins, are not metabolized to
      toxic epoxide intermediates, these results indicate promising new strategies for
      the design of non-toxic antioxidant coumarin-based drugs.

PMID- 18053337
TI  - In-vivo and in-vitro studies on the effect of Huang-Lian-Jie-Du-Tang on
      nimodipine transport across rat blood-brain barrier.
AB  - Huang-Lian-Jie-Du-Tang (HLJDT), an aqueous extract of Rhizoma Coptidis, Radix
      Scutellariae, Cortex Phellodendri and Fructus Gardeniae (3:2:2:3) is an important
      multi-herb remedy in traditional Chinese medicine (TCM). The aim of this study
      was to evaluate the effect of HLJDT on nimodipine transport across rat blood
      brain barrier (BBB). It was found that in-vivo the brain concentrations of
      nimodipine significantly increased when rats were pretreated with HLJDT. In
      vitro, the serum of HLJDT-treated rats increased the accumulation of nimodipine
      in primary cultured rat brain microvessel endothelial cells (rBMECs) and
      decreased the expression of P-glycoprotein (P-gp) on rBMECs. Our previous study
      showed that the peak concentration of baicalin and berberine in rats after
      administration of HLJDT was 5 mug mL(-1) and 10 ng mL(-1), respectively. This
      study showed that 5 mug mL(-1) baicalin significantly increased the accumulation
      of nimodipine in rBMECs, while 10 ng mL(-1) berberine had no effect on the
      accumulation of nimodipine in rBMECs. Both the in-vivo and in-vitro experimental
      findings indicated that HLJDT pretreatment may alter the transport of nimodipine
      across rat BBB.

PMID- 18053340
TI  - HIV-related pulmonary disorders: practice issues.
AB  - Pulmonary disease is the major cause of morbidity and mortality in infants and
      children infected with the human immunodeficiency virus (HIV). Diagnosis and
      management is often difficult in the resource-limited setting, especially as most
      HIV-related pulmonary disease presents in infancy or early childhood. Knowledge
      of the causes of pulmonary disease in HIV-infected children in that setting has
      improved considerably over the last decade, as has the availability of effective
      treatment for all HIV-infected children, such as cotrimoxazole preventive therapy
      and antiretroviral therapy. Important causes of acute bacterial pneumonia in HIV
      infected children include bacteria such as pneumococci, gram-negatives and
      staphylococci. Pneumocystis pneumonia is particularly common in HIV-infected
      infants and a common cause of death. Cytomegalovirus is also found frequently in
      infants with pneumonia, often as a co-infection with PcP. Tuberculosis (TB) is
      increasingly recognised as a common cause of acute pneumonia as well as chronic
      pulmonary disease in regions endemic for TB/HIV. Other important causes of
      chronic lung disease in HIV-infected children include lymphocytic interstitial
      pneumonitis and bronchiectasis. This review aims to address practical issues that
      health workers often face in the management of acute or chronic pulmonary disease
      presenting in HIV-infected children in the resource-limited setting.

PMID- 18053338
TI  - Modulatory effect of seabuckthorn leaf extract on oxidative stress parameters in
      rats during exposure to cold, hypoxia and restraint (C-H-R) stress and post
      stress recovery.
AB  - This study was carried out to examine the antioxidative potential, if any, of
      seabuckthorn leaf aqueous extract, administered orally in rats at a dose of 100
      mg kg(-1) both in single and five doses, 30 min before cold (5 degrees C)-hypoxia
      (428 mm Hg)-restraint (C-H-R) exposure. The effect of the extract was studied on
      lipid peroxidation and antioxidant parameters in liver and gastrocnemius muscle
      of rats on attaining the rectal temperature (T(rec)) of 23 degrees C during C-H-R
      exposure and after recovery (T(rec)37 degrees C) from C-H-R-induced hypothermia.
      In untreated rats exposed to C-H-R, there was a significant increase in
      malondialdehyde (MDA) levels in liver and muscle along with decreased activity of
      catalase (CAT) and glutathione-S-transferase (GST) in liver and muscle. Single-
      and five-dose extract treatment restricted the increase in liver and muscle MDA
      levels and five doses of extract treatment further improved the levels of liver
      antioxidants, viz. reduced glutathione (GSH), on recovery of T(rec)37 degrees C,
      increased superoxide dismutase (SOD) during exposure and recovery, normalized CAT
      activity in liver during C-H-R exposure and an increase on recovery of T(rec)37
      degrees C. The decreasing pattern of liver and muscle GST levels both in single
      dose and five-dose extract treated rats was similar to that in untreated rats.
      Results suggested that supplementation with seabuckthorn extract helps to reduce
      oxidative stress in liver and muscle of rats during C-H-R exposure and post
      stress recovery.

PMID- 18053341
TI  - Clinical profile of sickle cell disease in Yemeni children.
AB  - The clinical spectrum of sickle cell disease (SCD) in the Arabian Peninsula
      varies widely. This is the first report in Yemeni children. METHODS: A hospital
      based, cross-sectional study was undertaken in Al-Wahada Teaching Hospital in
      Aden of children under 16 years with homozygous (SS) SCD. RESULTS: Fifty-six
      (55%) were males. There were clinical manifestations in 20% by the age of 6
      months and in 67%, 88% and 92% by 1, 2 and 3 years, respectively. Dactylitis
      (hand-foot syndrome) was the most common presenting symptom and occurred in 54%
      of cases, followed by acute respiratory infections and other acute febrile
      illnesses. The main causes of hospitalisation were painful crisis (36%), anaemic
      crisis (16%) and acute chest syndrome (11%). Hepatomegaly was detected in 72% and
      splenomegaly in 40%. Cerebrovascular accident, cholelithiasis, hepatic crisis and
      leg ulcers each occurred in about 5% of patients. There was first- and second
      degree consanguinity in 31% and 16%, respectively, of patients' families.
      CONCLUSION: SCD is a serious problem, affecting children in Yemen from an early
      age. Disease course and severity were similar to that in Africans and American
      blacks and some reports from western Saudi Arabia. A screening programme linked
      to comprehensive medical care and genetic counselling is required to improve
      management and quality of life.

PMID- 18053342
TI  - Experience of anti-retroviral treatment for HIV-infected children in Malawi: the
      1st 12 months.
AB  - INTRODUCTION: Malawi is a resource-poor country in central southern Africa with
      an estimated 91,000 HIV-infected children. A national public sector
      antiretroviral treatment (ART) scale-up programme was commenced in 2004. AIM: The
      experience and results of the 1st 12 months of free ART for HIV-infected children
      from a public sector hospital in Malawi is reported. METHODS: Demographic and
      clinical data were collected at the commencement of ART and during treatment of
      all children who attended the clinic at Queen Elizabeth Central Hospital,
      Blantyre from 1 August 2004 to 31 July 2005. RESULTS: ART was prescribed for 238
      children during the 1st 12-month period. Of these, 196 were ART-naive and 42 had
      previously begun ART elsewhere. There were 128 (53.8%) males. Median age of the
      196 ART-naive children was 87 months (range 7-212); 173 (88.3%) had WHO clinical
      stage III disease and 23 (11.7%) had WHO clinical stage I or II disease. Weight
      for-age and weight-for-height Z-scores improved significantly with treatment. By
      31 July 2005, 194 (81.5%) of the 238 children who attended the clinic were alive
      and on treatment, 20 (8.4%) had died, 19 (8.0%) were lost to follow-up and 5
      (2.1%) had been transferred to other health facilities. CONCLUSIONS: In a
      resource-poor setting with only clinical monitoring available, children can
      feasibly and effectively be treated with ART. Lack of appropriate laboratory
      facilities, extra staff and paediatric drug formulations, although not ideal,
      should not prevent commencement of ART for children in such a setting.

PMID- 18053343
TI  - Micronutrients and T-cell subsets: a comparison between HIV-infected and
      uninfected, severely malnourished Rwandan children.
AB  - OBJECTIVE: To determine the levels of CD4+ cells and micronutrients in HIV
      infected and uninfected severely malnourished children. DESIGN: Cross-sectional
      study in two centres. SETTING: Children admitted to the malnutrition units in
      Kigali and Butare, Rwanda. PATIENTS: A total of 112 children aged 2 months to 5
      years presenting with severe malnutrition (weight for height Z- score -3 SD +/-
      oedema). Fifty-two (46.4%) were HIV-infected. METHODS: CD4+ counts, selenium,
      zinc and copper levels were measured. The percentage of CD4 cells was calculated
      as a proportion of total lymphocyte count. RESULTS: The mean age of the 52 HIV
      infected children (18 months) was lower than of the 60 uninfected children (26
      months) (p=0.01). Six (11.5%) of the HIV-infected had oedematous malnutrition
      compared with 50% of the uninfected group. The mean (SD) CD4+ count was 1054
      (780) in the HIV-infected and 1579 (721) in the uninfected group (p=0.001). The
      CD4+ count was also significantly lower in the HIV-infected group than in the
      uninfected group for the ages <12 mths (p=0.09), 12-24 mths (p=0.045) and >36
      mths (p=0.001). In HIV-infected children, 17% had severe immunosuppression (<15%
      CD4+ cells), 33% moderate (15-24%) and 50% had none (>25%) compared with 9%, 12%
      and 80% in the HIV-uninfected group, respectively (p<0.001). Approximately one
      third in both groups had low levels of selenium and zinc and 77% had raised
      levels of copper. In multivariate analysis there was significant correlation
      between selenium and CD4+ (r=0.36, p<0.001) in HIV-infected children and no
      correlation of zinc and copper to CD4+ %. In HIV uninfected children, CD4+ % was
      related to selenium (r=0.282, p=0.03) and to zinc (r=0.264, p=0.047) but not to
      copper. CONCLUSIONS: In severely malnourished children with HIV infection, low
      CD4+ levels are associated mainly with HIV infection. There was no significant
      difference in levels of selenium, zinc and copper between HIV-infected and
      uninfected children.

PMID- 18053344
TI  - Kawasaki disease in south India: a prospective, case-control study.
AB  - AIM: To describe the clinical and laboratory profile of Kawasaki disease in south
      India and compare patients with normal and abnormal cardiac status. METHODS: This
      was a nested case-control study. All patients admitted to Kanchi Kamakoti CHILDS
      Trust Hospital, Chennai with Kawasaki disease between January 2002 and March 2006
      were included. They were stratified into two groups: cases, who had abnormal
      echocardiography (ECHO), and controls, who had normal ECHO. All clinical and
      laboratory investigations, results of echocardiography and management were
      recorded and follow-up was organised. RESULTS: Of 56 patients, 36 (64.3%) were
      boys and 58.9% were under 3 years of age. Only 17.9% had an atypical
      presentation. Oral cavity changes and cervical lymphadenopathy were the most
      common clinical parameters and were detected in 85.7%. Thrombocytosis and
      elevated CRP on admission were seen in 41% and 100%, respectively.
      Echocardiography was abnormal in 27 (48.2%). Apart from raised CRP, which was
      higher in those with cardiac abnormality, the clinical and laboratory profiles
      were similar in the two groups. CONCLUSION: Kawasaki disease is not uncommon in
      south India. The clinical and laboratory profiles were similar between those with
      and without cardiac echocardiographic abnormality.

PMID- 18053345
TI  - Genital lesions complicating female genital cutting in infancy: a hospital-based
      study in south-east Nigeria.
AB  - BACKGROUND: Despite the global outcry against female genital cutting (FGC), the
      practice continues in many African communities. The morbidity of this practice on
      the girl child deserves more attention. OBJECTIVE: To determine the genital
      lesions complicating childhood FGC and the underlying factors that sustain this
      practice among the Igbos in south-east Nigeria. METHODS: Prospective evaluation
      of girls with genital complications of FGC between January 2003 and June 2005 at
      the Federal Medical Centre, Owerri, south-east Nigeria. The girls' mothers were
      interviewed at presentation and subsequent visits to determine their perception
      and attitudes towards FGC. RESULTS: The average age at presentation was 3.5 years
      (range 1-5) and the genital cutting procedures were performed 8-90 days after
      birth. The procedure was undertaken by traditional practitioners in 14 (66.7%)
      girls and by nurses in 7 (33.3%) girls. Twelve girls (57.1%) had type I genital
      cutting and nine (42.9%) type II. Inclusion clitoral dermoid cyst and labial
      fusion were the complications in 13 (61.9%) and eight (38.1%), respectively.
      Treatment involved complete excision of the cysts and operative division of the
      labial fusion. Post-operative complications were wound infection (5) and labial
      adhesion (2). With duration of admission ranging from 3 to 5 days, the average
      cost of managing each child was $120. Of the girls' mothers, 15 (71.4%) had been
      educated to secondary level and 17 (80.1%) were aware of the campaign against
      FGC. Regrettably, all the mothers had genital cutting themselves during childhood
      and 13 (61.9%) stated that they would like to perpetuate the practice for socio
      cultural reasons. Despite this, they all volunteered that FGC is enforced by the
      child's paternal relations. CONCLUSION: Childhood FGC contributes to appreciable
      morbidity among girls, a large proportion of whom are not managed in a hospital
      setting. The cost of managing these complications can be enormous, especially in
      low-resource settings. Girl child education to tertiary level and the involvement
      of traditional rulers and local decision-makers in the campaign against FGC might
      help to eradicate the practice.

PMID- 18053346
TI  - Socio-economic status and hearing loss in chronic suppurative otitis media in
      Nigeria.
AB  - BACKGROUND: Hearing loss is reported in about 50% of cases of chronic suppurative
      otitis media (CSOM). AIM: To report the prevalence, type and severity of hearing
      loss in CSOM and identify risk factors. METHODS: A prospective study of hearing
      loss in CSOM was undertaken in University College Hospital, Ibadan, two general
      hospitals and two primary health care centres, all in densely populated, semi
      urban areas in south-west Nigeria. Controls were selected from school children,
      hospital workers' children and children whose parents were visiting the
      hospitals, all of whom claimed that there had been no episode of otitis media in
      the past. An oral questionnaire was administered to all, followed by audiometry
      and examination of the ear, nose and throat in study children. RESULTS: There
      were 189 CSOM subjects and 100 controls aged between 4 and 150 months [mean (SD)
      59.25 (44.55), 173 girls and 116 boys, M:F 1.5:1]. The prevalence of hearing loss
      in CSOM was 89/189 (47%) and was conductive in 73/89 (82%) and sensorineural
      (SHL) in 16/89 (18%). Of the subjects with hearing loss, 72% had had otitis media
      during the 1st year of life. Of the 89, 61 (69%) were of low social class, 13/37
      (35%) were middle class and 15/63 (24%) upper class. The duration of CSOM ranged
      from 4 weeks to 12 years [mean (SD) 4 yrs (2.04)] and from 5 to 12 years in those
      with SHL [mean (SD) 9 yrs (6.21)]. There was significant correlation between
      socio-economic status and hearing loss (r=0.138, p=0.02) while no correlation was
      found with upper respiratory infection (r=0.054, p=0.36), age of onset (r=0.037,
      p=0.62) or frequency of attacks (r=-0.068, p=0.35). CONCLUSION: About one fifth
      of patients with CSOM have SHL. Early diagnosis and management of CSOM is
      imperative to improve outcome. CSOM is strongly associated with low socio
      economic status.

PMID- 18053347
TI  - Performance of a rapid antigen test for the diagnosis of congenital malaria.
AB  - OBJECTIVE: To assess the performance of OptiMAL, a rapid malaria antigen capture
      dipstick, in diagnosing congenital malaria. METHODS: Live newborns aged 0-3 days,
      delivered at Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria
      between August 2004 and January 2005, were screened for malaria parasitaemia with
      an immunochromatographic test (OptiMAL) and blood film microscopy. OptiMAL
      detects plasmodium lactate dehydrogenase (pLDH). RESULTS: Twenty-one of 192
      newborns (10.9%) were diagnosed with congenital malaria by blood film microscopy.
      The OptiMAL test was negative in all infants. CONCLUSION: OptiMAL rapid malaria
      antigen capture dipstick might not be useful for diagnosing malaria parasitaemia
      in newborns. Blood film microscopy remains the gold standard for the diagnosis of
      congenital malaria.

PMID- 18053348
TI  - Kawasaki disease presenting as hepatitis.
AB  - Kawasaki disease (KD) presenting with an acute hepatitic picture is exceedingly
      rare. A 3.5-year-old girl presented with acute hepatitis and went on to satisfy
      the criteria for the diagnosis of KD for which she was treated. There were no
      cardiac abnormalities or sequelae.

PMID- 18053349
TI  - Cutaneous anthrax involving the genital area.
AB  - A 5-year-old girl was admitted with a lesion of the labia majora which was found
      to be owing to anthrax. She had been licked on the hand by a sick cow (which
      subsequently died) 5 days prior to admission to a health clinic and 8 days before
      admission to hospital.

PMID- 18053350
TI  - Churg-Strauss syndrome presenting as an abdominal mass in a non-asthmatic child.
AB  - A 2-year-old boy presented with an abdominal mass and was diagnosed as Churg
      Strauss syndrome (CSS). There was no history of asthma. He developed fatal gastro
      intestinal disease, despite treatment with corticosteroids and cyclophosphamide.
      CSS is extremely rare in young children and gastro-intestinal involvement might
      carry a worse prognosis than in adults.

PMID- 18053351
TI  - An unusual complication of femoral vein catheterisation: pneumoperitoneum.
AB  - A 2-month-old girl with severe pneumonia required a central venous line. Femoral
      vein catheterisation was attempted but insertion was difficult. Pneumoperitoneum
      developed, which is a rare complication of femoral vein catheterisation. It is
      important when undertaking femoral vein catheterisation to use the correct
      landmarks in the femoral triangle below the inguinal ligament and an appropriate
      size of catheter.

PMID- 18053352
TI  - Vitamin D deficiency and rickets: possible role of maternal vitamin D deficiency.

PMID- 18053353
TI  - [Smoking in health care workers].

PMID- 18053354
TI  - [Dissociated deviation. A strabismus of cortical origin].
AB  - BACKGROUND: We undertook this study to determine the cortical alterations related
      to the origin of dissociated deviation. METHODS: This was a prospective,
      descriptive and observational study that included 10 children with diagnosis of
      dissociated horizontal deviation, without previous evidence of neuronal damage.
      Manual, cerebral and ocular dominance were determined, as well as sensorial state
      and visual perceptual profile. Cortical response to different stimuli was
      analyzed: luminous, hyperventilation, slow and saccadic movements of pursuit,
      gaze and stare through cerebral mapping and neurometric EEG. The biochemical
      composition to the visual cortex by means of magnetic resonance spectroscopy was
      also investigated. RESULTS: The following alterations were demonstrated: a)
      neuroelectric: dysynchronic, paroxysms and/or lentification; b) neurometabolic:
      elevation of lactate, decrease of N-acetylaspartate and loss of the
      creatine/choline relationship; c) sensorial: suppression and amblyopia; d)
      perceptual vision: under-yield in visual abilities; e) motor: horizontal and
      vertical dissociated deviation; f) optometric: hyperopic astigmatism.
      CONCLUSIONS: The study suggests that dissociated deviation has a cortical origin
      and is related to epileptogenic disease.

PMID- 18053355
TI  - [Ultrastructure of the anterior capsule of the lens in different pathologies].
AB  - BACKGROUND: We undertook this study to compare the ultrastructural analysis of
      capsules of normal lenses (phacorefractive procedures) and those of other types
      of cataracts also such as senile cataracts, with trans-surgical staining.
      METHODS: Capsule samples were obtained by circular continuous capsulorhexis
      during phacoemulsification procedures. All samples were fixed and conventionally
      processed for light- and transmission-electron microscopy analysis. RESULTS:
      Seventeen analyzed samples were grouped as follows: a) phacorefractive (n = 2),
      b) senile cataract (n = 3); c) senile diabetic (n = 3), d) pseudoexfoliation
      syndrome (n = 3); e) stained with trypan blue (n = 2), f) indocyanine green (n =
      2), and g) gentian violet (n = 2). According to morphological analysis, all
      samples of cataract demonstrated lacunae zones between epithelial cells.
      Filamentous annular bodies were found near the epithelium in capsule of senile
      cataracts. Senile diabetic cataract samples showed more abnormalities in
      epithelial morphology; specifically we found conformation of two or three layers
      of epithelial cells. Samples stained with trypan blue showed a regular basal
      membrane and minor loss of epithelial cells than other trans-surgical stain
      techniques. CONCLUSIONS: After an exhaustive medical literature search, we
      published the first report about the observation of filamentous annular bodies
      near the epithelium in capsules of senile cataracts. Additionally, it is
      important to note the presence of stratification of the epithelium at the
      anterior pole of capsules from diabetic patients.

PMID- 18053356
TI  - [Primary melanoma of the oral mucosa. Experience of the Oncology Hospital of
      Centro Medico Nacional Siglo XXI].
AB  - BACKGROUND: Primary intraoral melanoma is extremely rare and carries a poor
      prognosis. Treatment of choice remains controversial. Our aim was to define the
      clinical features of this disease and to evaluate treatment methods. METHODS: We
      retrospectively studied 14 patients with primary malignant melanoma of the oral
      cavity seen at the Oncology Hospital of the Mexican Institute of Social Security
      (IMSS), 21st Century National Medical Center (CMN-SXXI) between 1991 and 2005.
      The main variables studied were clinical findings, response to therapy, and
      outcome. RESULTS: In five males (35.7%) and nine females (64.3%) with a mean age
      of 65 years, tumor locations included hard palate (nine cases), maxillary gingiva
      (three cases), hard/soft palate (one case) and lip (one case). Pre-existing
      melanotic pigmentation was present in two patients. Nine patients were in stage
      I, four in stage II, and one was in stage III. Surgical excision was the primary
      treatment in 11 cases; four patients underwent simultaneous neck dissections. All
      patients in stage II received adjuvant radiation therapy. After a 3-year follow
      up, three patients of those presenting stage I are still alive (33.3%, 3/9
      cases), and all patients in stages II and III eventually died of the disease.
      CONCLUSIONS: Early diagnosis of pigmented lesions in the mouth along with
      adequate tumor resection may improve the prognosis of this disease; however, in
      advanced disease stage it may be reasonable to infer that major improvements in
      outcome after treatment of malignant melanoma of the oral cavity may not be
      carried out until more effective systemic therapy becomes available.

PMID- 18053358
TI  - [Clinical problem solving as a measurement instrument in a diploma course for
      respiratory technicians].
AB  - BACKGROUND: We undertook this study to consider the gaps in the training of
      clinical respiratory insufficiency as relates to students enrolled in a technical
      professional course in respiratory therapy. METHOD: An instrument was constructed
      and validated to evaluate clinical aptitude, integrated by four clinical cases of
      respiratory insufficiency. Six indicators were defined and 140 statements were
      elaborated, after two rounds with five technicians in respiratory therapy with
      experience in the care of patients with respiratory insufficiency in intensive
      care units, 90 statements remained. The instrument was applied in a pilot group
      of 31 students using Kuder Richardson formula 21 and the consistency was (0.80).
      Clinical aptitude of students was described on an ordinal scale from very low to
      very high. Categories were established from qualifications calculated for the
      expected chance effects. RESULTS: On comparing initial and final qualifications,
      there were statistically significant differences (p <0.005). CONCLUSIONS:
      Clinical aptitude was developed in most students enrolled in the training course.
      Although a promotional educational participation strategy was not planned, we are
      in agreement that education and training of the coordinating professors
      contributed to achieving the goals.

PMID- 18053357
TI  - [Heller's myotomy with fundoplication by endoscopic surgery].
AB  - BACKGROUND: We undertook this study to present a 5-year experience in
      laparoscopic treatment of achalasia using Heller myotomy with an antireflux
      technique. METHODS: Fourteen patients with diagnosis of achalasia were included.
      We analyzed age, sex, symptoms, endoscopy, radiology and manometry results, pre-
      and postoperative treatment, fundoplication technique, surgical time and Visick
      Score. RESULTS: Heller myotomy with an antireflux technique was carried out in 14
      patients: Dor was performed in eight patients, Toupet in four patients, and
      Nissen in two patients. Average surgical time was 145 min, which decreased to 130
      min in those patients who underwent Dor fundoplication. Oral feeding was started
      1.5 days after surgery and the average hospital stay was 2.5 days. Visick Score
      was as follows: grade I-six patients (42.8%, Dor four patients, Toupet one
      patient, Nissen one patient); grade II-four patients (28.5%, Dor three patients,
      Toupet one patient); grade IIIA-two patients (14.2%, Dor two patient); grade IVA
      one patient (7.1%, Toupet); grade IVB-one patient (7.1%, Nissen-Rossetti).
      CONCLUSIONS: Heller myotomy is currently the gold standard in the treatment of
      achalasia and should be performed with an antireflux procedure. In our series, we
      have found that there are fewer complications with Dor fundoplication, the
      procedure is easier (implying shorter surgical time), and it offers the best
      results as compared with other antireflux techniques.

PMID- 18053359
TI  - [Pediatric laparoscopic cholecystectomy].
AB  - BACKGROUND: We undertook this study to evaluate the results of surgical treatment
      of symptomatic cholelithiasis through laparoscopic cholecystectomy in a series of
      47 consecutive pediatric patients. METHODS: During a 5-year period (2001-2005) we
      performed laparoscopic cholecystectomy in 47 patients <18 years old in one
      institution by the same surgical team. The population was comprised of 41 girls
      and 6 boys (age range: 6-18 years). All had symptomatic cholelithiasis confirmed
      at ultrasound examination. Associated pathology was studied in each case. The
      surgical procedure consisted of a four-port laparoscopic cholecystectomy under
      CO(2) pneumoperitoneum. No other concomitant procedure was performed in any case.
      RESULTS: Median age was 14.6 years old. The youngest patient of the series had a
      hematological disease. In girls we identified obesity in 62.5% of patients, with
      a body mass index (BMI) of 26.6 kg/m(2) (SD 3.0) vs. 21.5 kg/m(2) (SD 3.0) in
      boys (p <0.05), 30% of the girls had a positive medical history for pregnancies
      (range 1-3) and 15% regularly used oral contraceptives. All cases were
      symptomatic and 13% suffered from acute biliary pancreatitis. Average surgical
      time was 59.8 min, the conversion rate was 2.1% and the most frequent surgical
      complication was gallbladder rupture. No major morbidity was observed as well as
      no mortality. Postoperatively, all patients were asymptomatic, with a minimum
      follow-up time of 6 months. CONCLUSIONS: Laparoscopic cholecystectomy was highly
      effective in cases of symptomatic cholelithiasis. Etiologically, females showed
      risk factors for cholelithiasis similar to those usually observed in adults.
      Probably in the near future the incidence of cholelithiasis will increase in this
      age group. Pediatric surgeons should be familiarized with the minimal access
      technique to treat this disease.

PMID- 18053360
TI  - [Orthotopic liver transplantation: results at a single center].
AB  - BACKGROUND: We undertook this study to describe the results of hepatic orthotopic
      transplant. Patient characteristics, implants, and patient evolution after
      transplant were studied. The study was conducted at a third-level medical
      facility in Mexico. METHODS: The files of 49 patients who had a liver transplant
      were reviewed from July 17, 1999, through November 30, 2006. We also analyzed
      pretransplant status and status of the hepatic implant at the time of the
      transplant. Finally, patient evolution was reported postoperatively. RESULTS:
      Fifty transplants were carried out in 49 patients (one man was retransplanted and
      one women had a liver and kidney transplant). There were 35 women (71.43%) and 14
      men (28.57%). Ages of the patients were between 2 and 61 years (average 40.40
      years). The most frequent causes resulting in transplants were cirrhosis caused
      by hepatitis C virus (HCV) and autoimmune cirrhosis: 28 cases (56%) and 7 cases
      (14%), respectively. Four patients (8%) died from surgery-related complications
      and 11 patients died (22%) from nonsurgical complications. Patient survival
      according to Child-Pugh is as follows: Child-Pugh A: 3/4 patients (75%), Child
      Pugh B: 17/24 patients (70%), Child-Pugh C: 15/22 patients (68%). Preoperative
      survival was 35 patients (70%), 1-year survival was 32 patients (64) and 5-year
      survival was 29 patients (58%). CONCLUSIONS: Survival rates of our patients are
      acceptable even though the majority of those transplanted had severe hepatic
      insufficiency and others had diabetes and portal thrombosis.

PMID- 18053361
TI  - [Laparoscopic splenectomy: 7-year experience].
AB  - BACKGROUND: Laparoscopic splenectomy is an effective and safe technique in the
      management of benign splenic pathologies. METHODS: We reviewed our 7-year
      experience to evaluate utility and safety of this procedure. RESULTS:
      Laparoscopic splenectomy was performed in 20 patients (13 women, 7 men), with a
      mean age of 49 years. Pathology included 19 cases of idiopathic thrombocytopenic
      purpura (ITP) and one case of autoimmune hemolytic anemia. Mean operative time
      was 165 min, including anesthetic procedure. There was only one conversion to
      open surgery. Accessory spleens were detected in 15% of patients. Early remission
      of hematological disorders was achieved in 70% of the cases and long-term
      remission in 90%. The complications rate was 20%, including two cases of
      subphrenic hematoma, one case of acute focal pancreatitis and one case of
      thrombosis of the portal venous system; all recovered with no sequelae. Mortality
      rate was 0%. CONCLUSIONS: Laparoscopic splenectomy obtains results identical to
      those of open surgery in terms of efficacy and safety but with the benefits of
      laparoscopic surgery. Therefore, it should be considered as the procedure of
      choice for the treatment of benign hematological pathologies unresponsive to
      medical therapy.

PMID- 18053362
TI  - [Papillary cardiac fibroelastoma. An unusual presentation].
AB  - BACKGROUND: Papillary fibroelastoma is a rare benign tumor characterized
      morphologically since first being described in 1976. Nevertheless, this tumor can
      be presented with a variety of clinical manifestations, making diagnosis
      challenging for the physician. There are no gender or age preferences but it is
      diagnosed by site of presentation along with macro- and microscopic
      characteristics. CASE REPORT: We report the case of a male patient with a history
      of type 2 diabetes mellitus and arterial hypertension who was admitted to the
      hospital with a diagnosis of ischemic heart disease accompanied by sustained
      ventricular tachycardia. Echocardiogram reported degree I diastolic dysfunction,
      apical ventricular aneurysm, and unusual apical tumor of the septum and left
      ventricle. DISCUSSION: Primary heart tumors have an incidence of 0.0017%. The
      most common symptoms are chest pain, syncope, dyspnea and arrhythmias. Diagnosis
      is accomplished incidentally by echocardiography, which is usually carried out
      for other reasons. Surgical procedure of choice is total tumor resection along
      with valve repair or replacement, if necessary, and in some cases cardiac
      endothelium resection and repair, with or without pericardium patch replacement.
      CONCLUSIONS: Papillary fibroelastoma is rare but is a recognized cause of embolic
      phenomena. Rapid identification followed by surgical resection is curative,
      precise and well tolerated by the patient.

PMID- 18053363
TI  - [Endoluminal treatment for traumatic aortic rupture. Case report and literature
      review].
AB  - Traumatic rupture of the thoracic aorta is a near-lethal event presenting on
      scene mortality rates of 80% and 60-80% perioperatively with an overall survival
      rate of 15%. Conventional treatment includes thoracotomy with aortic clamping and
      aortic replacement but this implies high complication and mortality rates with
      extended inpatient care. Endoluminal treatment has recently become an attractive
      treatment option with advantages such as lower death and complication rates as
      well as shorter inpatient care. We present an 18-year-old female victim of a
      frontal automobile crash who presented mediastinal enlargement and underwent CT
      evaluation confirming pericardial effusion, left hemothorax and a contained
      traumatic rupture of the thoracic aorta. She was sent to our hospital where
      aortography was performed identifying the injury, and a preperitoneal left iliac
      artery approach was made to insert a Medtronic Talent 24F endograft. Under
      fluoroscopic guidance the graft was placed below the subclavian ostium. There was
      no endoleak after the procedure. A left iliac-femoral bypass was performed and a
      chest tube was inserted. The patient was managed in the ICU, being later operated
      by reconstructive and orthopedic surgeons for injuries related to the initial
      trauma. The patient was released from the hospital on the 10th postoperative day
      after a satisfactory evolution. We present also a brief review of recent
      articles.

PMID- 18053364
TI  - [Positron emission tomography and computed tomography (PET/CT) in lung cancer].
AB  - BACKGROUND: Lung cancer is the most frequent cause of death due to neoplasm in
      Western populations, with >660,000 new diagnoses of lung cancer per year
      according to the World Health Organization. METHODS: We undertook this study to
      emphasize the role of positron emission tomography to all health care
      professionals involved in lung cancer diagnosis. RESULTS: There are false
      negatives with PET-(18)FDG in carcinoids and broncheoalveolar carcinoma in almost
      40% of the cases. One relatively common cause of false positives is the vocal
      cord and adjacent muscles contralateral and compensatory to the lung lesion that
      show an increased uptake of (18)FDG because of lesions in the laryngeal nerve by
      the tumor or secondary to surgery. It should not be confounded with metastases.
      CONCLUSIONS: There is sufficient scientific evidence pointing to the usefulness
      of PET studies and its evolution to PET/CT, especially in patients with lung
      cancer. This can resolve doubts by the oncologist and patient when there is a
      suspicious malignant lesion by the following: characterizing solitary pulmonary
      nodules (benign or malignant), localizing the optimal site for the biopsy,
      diagnosis of the primary tumor for initial staging, evaluation of mediastinal
      involvement and distant metastasis, evaluate and restage residual tumor,
      assessment of recurrence, monitoring response, prognostic prediction and
      radiotherapy planning.

PMID- 18053365
TI  - [Thrombophilia, autoimmunity, and perioperative thromboprophylaxis].
AB  - Thrombosis is observed in several areas of medicine. Equilibrium between pro- and
      anticoagulant factors is required for maintaining blood flow. Tissue injury from
      multiple causes may induce coagulum formation mediated by coagulation pathway
      activation. Tissue factor (F III) + F VIIa interacts with both platelet and
      endothelial cell receptors. This coagulation model displays four stages: a)
      initiation, b) amplification, c) propagation and d) stabilization. Development of
      thrombosis is associated with either primary or hereditary and acquired factors.
      Primary thrombophilia is determined genetically by a hypercoagulative state shown
      by loss of natural anticoagulant activity, such as antithrombin III, C, S protein
      or procoagulant activity gaining resistance to activated C protein: factor V
      (Leiden), prothrombin and methylenetetrahydrofolate reductase mutations. Acquired
      thrombophilia mainly relates to an autoimmune condition such as the presence of
      anticardiolipin antibodies or lupus anticoagulant. Surgical procedures enhance
      mechanisms that predispose to thrombosis, e.g., acidosis, hypothermia, plasma
      expanders, extracorporeal circulation, duration of surgical procedure, and tissue
      manipulation. Adequate classification of the patient's thrombosis risk and
      adequate use of primary and secondary prophylactic recommendations in these
      groups of patients is necessary.

PMID- 18053367
TI  - Editor's view.

PMID- 18053366
TI  - [Letter to the editor].

PMID- 18053369
TI  - Mentoring for surgical skills: a tool to share the workload.

PMID- 18053370
TI  - Does sex affect residency application to surgery?
AB  - OBJECTIVE: To determine whether women are proportionately underselected at the
      level of the annual residency match. METHODS: Data were obtained from the Royal
      College of Physicians and Surgeons of Canada and the Canadian Residency Matching
      Service. The odds of men being rejected from their top choice of surgical
      discipline were compared with the corresponding odds for women for the surgical
      specialties of general surgery, orthopedic surgery, neurosurgery, otolaryngology,
      urology, cardiac surgery and plastic surgery. RESULTS: Women continue to be
      underrepresented among surgery residents and surgeons in practice; however, the
      number of women has increased. Neither sex was overselected among the surgical
      specialties examined. CONCLUSIONS: There was no evidence of overselection of
      either sex at the level of the annual resident selection committee.

PMID- 18053371
TI  - Injury patterns and outcomes associated with elderly trauma victims in Kingston,
      Ontario.
AB  - OBJECTIVE: To characterize the common injuries incurred by elderly trauma victims
      and to identify the most frequent complications and outcomes. METHODS: We
      undertook a retrospective descriptive chart review of 125 consecutive patients
      who were over age 65 years and who were admitted to an academic hospital in
      Kingston, Ontario, over a 3-year period with an injury severity score (ISS) > 12.
      Complete data about the mechanism of injury (MOI), age, date, sex, specific
      injury, principal and secondary diagnoses, comorbid conditions, intensive care
      unit (ICU) and hospital length of stay and discharge disposition were recorded
      for 99 of these patients. RESULTS: Elderly trauma cases accounted for 125 of the
      total 460 trauma admissions over 3 years. For that same period, more than 50% of
      trauma deaths occurred among elderly patients, of whom 65 were men and 34 were
      women. Their mean age was 77 (standard deviation [SD] 6) years, with an age range
      of 66-95 years. The average ISS score was 23 (SD 13), with a range of 12-75. MOI
      included falls (64%), motor vehicle collision (27%), injury from machinery (3%),
      injury from natural and environmental causes (2%), suicide or self-inflicted
      injury (3%) and burns (1%). The mean length of stay was 14.6 days, but this
      ranged from 1 to 111 days. Of the 99 patients, 14 were admitted to the ICU for a
      total of 37 days, and 9 of these died. Of the total of 67 (67%) patients who were
      discharged from hospital, 46% were discharged home and 32% died. Falls accounted
      for the most frequent MOI, followed by motor vehicle collisions. The most common
      injury in the falls group was subdural hematoma, whereas fractures were the most
      common injuries in the motor vehicle collision group. The most frequent
      complications included urinary tract infections and aspiration pneumonias.
      Neither age nor MOI was correlated with injury severity. Increasing age and
      injury severity were predictors for complications and mortality while in
      hospital. CONCLUSIONS: Despite severe injuries, most elderly patients can survive
      traumatic injuries. The data suggest that, although elderly patients are prone to
      incur complications and have greater risk of dying as a result of their injuries,
      most of these patients will survive their traumatic accidents. The data also show
      that nosocomial complications play a significant role in the risk of mortality in
      elderly trauma victims.

PMID- 18053372
TI  - Patient satisfaction with outpatient lumbar microsurgical discectomy: a
      qualitative study.
AB  - OBJECTIVE: Lumbar microsurgical discectomy was traditionally done as an inpatient
      procedure, but over the last decade, there has been an ever-expanding shift
      toward outpatient lumbar microdiscectomy (OLM). We have been performing OLM since
      1997 (MB) and 2002 (EMM), but no study of patient satisfaction has been carried
      out to date. the objective of our study was to investigate patient satisfaction
      with the experience. METHODS: Between September 2004 and March 2005, we carried
      out a qualitative case study at Toronto Western Hospital, involving interviews
      with 28 patients who had recently undergone OLM. The protocol was approved by the
      institutional Research Ethics Board, and informed consent was obtained from each
      participant. Interviews were transcribed and stored anonymously and subjected to
      modified thematic analysis by 5 reviewers. RESULTS: Analysis of the interviews
      yielded several overarching themes: 1) patients are surprised that back surgery
      can be done on an outpatient basis; 2) the amount and quality of information they
      receive is satisfactory; 3) the overall experience is positive; 4) trust in one's
      surgeon is important; and 5) some patients have significant back pain in the
      early postoperative period. CONCLUSIONS: Most patients appreciate the need for
      the health care system to save money where possible so that it can be spent in
      other, more resource-intensive areas. Outpatient lumbar microdiscectomy satisfies
      this goal while retaining high patient satisfaction rates. Qualitative research
      can yield substantial insight, which will improve the experience for future
      patients. Qualitative research is rare in the surgical literature and can answer
      questions quantitative research methods cannot.

PMID- 18053373
TI  - Chest tube complications: how well are we training our residents?
AB  - BACKGROUND: Thoracic trauma is commonly treated with tube thoracostomy. The
      overall complication rate associated with this procedure is up to 30% among all
      operators. The primary purpose of this study was to define the incidence and risk
      factors for complications in chest tubes placed exclusively by resident
      physicians. The secondary objective was to outline the rate of complications
      occult to postinsertional supine anteroposterior (AP) chest radiographs (CXRs).
      METHODS: Over a 12-month period at a regional trauma centre, we retrospectively
      reviewed all severely injured trauma patients (injury severity score >or= 12) who
      underwent tube thoracostomy (338/761 patients). Insertional, positional and
      infective complications were identified. Patients were assessed for complications
      on the basis of resident operator characteristics, patient demographics,
      associated injuries and outcomes. Thoracoabdominal CT scans and corresponding
      CXRs were also used to determine the rate of complications occult to
      postinsertional supine AP CXR. RESULTS: Of the patients, 338 (44%) had CXR and CT
      imaging. Out of 76 (22%) chest tubes placed by residents in 61 (18%) patients
      (99% of whom had blunt trauma injuries), there were 17 complications; 6 (35%)
      were insertional; 9 (53%) were positional and 2 (12%) were infective. Tube
      placement outside the trauma bay (p = 0.04) and nonsurgical resident operators (p
      = 0.03) were independently predictive of complications. The rates of
      complications according to training discipline were as follows: 7% general
      surgery, 13% internal and family medicine, 25% other surgical disciplines and 40%
      emergency medicine. Resident seniority, time of day and other factors were not
      predictive. Six of 11 (55%) positional and intraparenchymal lung tube placements
      were occult to postinsertional supine AP CXR. CONCLUSIONS: Chest tubes placed by
      resident physicians are commonly associated with complications that are not
      identified by postinsertional AP CXR. Thoracic CT is the only way to reliably
      identify this morbidity. The differential rate of complications according to
      resident specialty suggests that residents in non-general surgical training
      programs may benefit from more structured instruction and closer supervision in
      tube thoracostomy.

PMID- 18053375
TI  - Radiology for the surgeon. Musculoskeletal case 40.

PMID- 18053374
TI  - Use of octreotide for the prevention of pancreatic fistula after elective
      pancreatic surgery: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the effectiveness of octreotide in preventing postoperative
      pancreatic fistula. Pancreatic fistula is one of the most common complications
      after elective pancreatic surgery. Several clinical trials have evaluated the use
      of octreotide to prevent the development of pancreatic fistula after pancreatic
      surgery with conflicting recommendations. METHODS: We undertook a meta-analysis
      of 7 identified randomized controlled trials, reporting comparisons between
      octreotide and a control. The primary outcome was the incidence of postoperative
      pancreatic fistula, and the secondary outcome was the postoperative mortality.
      RESULTS: Seven studies, involving 1359 patients, met the inclusion criteria for
      this review. In these studies, sample sizes ranged from 75 to 252 patients. In
      total, 679 patients were given octreotide and 680 patients formed the control
      group. Perioperative octreotide is associated with a significant reduction in the
      incidence of pancreatic fistula after elective pancreatic surgery, with a
      relative risk of 0.59 (95% confidence interval 0.41-0.85, p = 0.004). However,
      this risk reduction was not associated with a significant difference in
      postoperative mortality (p > 0.05). CONCLUSIONS: The review revealed that
      perioperative octreotide is associated with a significant reduction in the
      incidence of pancreatic fistula after elective pancreatic surgery. However, this
      risk reduction was not associated with a significant difference in postoperative
      mortality; further studies are warranted to confirm the results of this
      metaanalysis and to define which patient subgroups might benefit the most from
      prophylactic octreotide administration.

PMID- 18053376
TI  - Surgical technique. The ambidextrous surgeon's knot: an alternate way to tie the
      surgeon's knot.

PMID- 18053378
TI  - Canadian Association of General Surgeons and American College of Surgeons
      Evidence Based Reviews in Surgery. 23. ASCO recommended guidelines for sentinel
      lymph node biopsy for early-stage breast cancer. Evidence-based medicine. A new
      approach to teaching the practice of medicine.

PMID- 18053377
TI  - The efficacy and risks of using povidone-iodine irrigation to prevent surgical
      site infection: an evidence-based review.

PMID- 18053379
TI  - William D. Stevenson: Atlantic Canada's first neurosurgeon.
AB  - The origins of neurosurgical services in Atlantic Canada are tied to the
      individual efforts of William D. Stevenson. Born in Hamilton, Ontario, Stevenson
      completed his senior matriculation in Dunnville, Ontario, before studying
      medicine at the University of Toronto. He completed the Gallie surgical course in
      Toronto and then spent 1 year training with Edward Archibald at McGill
      University. After working for 2 years with the Canadian Mobile Neurosurgical Unit
      in Europe during the Second World War, Stevenson undertook formal neurosurgical
      training with Kenneth G. McKenzie, Canada's first neurosurgeon. Stevenson was
      thereafter recruited to Halifax to start the neurosurgical service at the
      Victoria General Hospital in January 1948, and he remained head of the division
      for the next 26 years. His pioneering work laid the foundations for the
      establishment of a major academic neurosurgical service at Dalhousie University
      and was crucial for the establishment of neurosurgery in Atlantic Canada. After
      his retirement, Stevenson moved back to Ontario and began his second career,
      transferring his passion for neurosurgery to oil painting. His legacy to
      neurosurgery in Atlantic Canada will be remembered in perpetuity with the annual
      Neurosurgery Resident Research Award at Dalhousie University, established and
      named in his honour. This paper focuses on Stevenson's life and work in
      neurosurgery as Atlantic Canada's first neurosurgeon.

PMID- 18053380
TI  - Vulvar seborrheic keratosis.

PMID- 18053382
TI  - Postpartum pain relief: a randomized comparison of self-administered medication
      and standard administration.
AB  - OBJECTIVE: To compare pain relief in postpartum women receiving analgesia
      administered by nurses with the relief achieved by use of self-administered
      medication (SAM). METHOD: This randomized trial included women in spontaneous or
      induced labour or admitted for elective Caesarean section (CS). Women were
      stratified according to the mode of delivery. In the standard group, nurses
      administered the medications. In the SAM group, women kept the medications at the
      bedside and recorded each dose. The women were asked to record their pain level
      with a validated scale before and one hour after the administration of analgesia.
      A global pain score was calculated using the mean of these scores, and the
      satisfaction of patients and nurses with the process was recorded. RESULTS: We
      recruited 345 women for the study. Eleven women (3.15 %) were lost to follow-up.
      We analyzed data from 197 women in the vaginal delivery arm and 133 women in the
      CS arm. There was no difference between the global pain scores before and one
      hour after the administration of analgesia in each group, independent of the mode
      of delivery. Women who used SAM and had a vaginal delivery were significantly
      more likely to have used no medication (P = 0.02) or to have used acetaminophen
      (P = 0.008), and fewer of these women took naproxen (P = 0.05). No significant
      difference was seen in women who had CS. Narcotic use was similar in each group.
      Women who used SAM were more likely to indicate that they would choose this
      method again and recommend it to others. The level of satisfaction with SAM
      expressed by nurses did not change after the study. CONCLUSION: Postpartum pain
      relief was similar for women who had standard administration of medication by
      nurses and those who had SAM. More women using SAM used either no medication or
      acetaminophen only, and more women using SAM were highly satisfied with their
      method of pain relief. Use of self-administered medication should be considered
      for every postpartum unit.

PMID- 18053383
TI  - Addressing wait times for endometrial cancer surgery in Ontario.
AB  - OBJECTIVE: Wait times for cancer surgery in Ontario have increased over the last
      decade. We reviewed trends in wait times for endometrial cancer surgery from 1996
      to 2000 and identified determinants that may need to be addressed in order to
      reduce these wait times. METHODS: The study population included women diagnosed
      with endometrial cancer (ICD-9 codes 179 or 182) prior to surgery. Surgical wait
      time was defined as the interval between date of diagnosis and hospital admission
      for surgery. Univariate analyses assessed demographic, treatment, and hospital
      factors associated with wait times. A multilevel linear regression model was
      created to account for clustering of patients at the hospital level and regional
      level defined by local health integration networks (LHINs). Effects of covariates
      were expressed as estimates of the median proportional change in wait time.
      RESULTS: There were 2042 cases in this analysis. Mean wait time increased from 32
      to 40 days (P = 0.0012). Prolonged wait times were associated with age > 70
      years, presence of comorbidities, and surgery performed at a teaching hospital
      and by a gynaecologic oncologist. Wait times were not associated with income
      level or region of residence defined by LHIN. CONCLUSION: Wait times for
      endometrial cancer surgery have increased significantly in Ontario. Determinants
      of these prolonged wait times need to be addressed, and criteria for referral to
      a teaching hospital and gynaecologic oncologist should be developed to ensure
      that local health integration networks provide equal and timely access to care.

PMID- 18053385
TI  - Increasing folate supplementation for selected groups of Canadian women.
AB  - After review of current evidence related to the potential risks and benefits of
      folic acid supplementation, we conclude that unless clinicians can be assured
      that pregnant women will reliably use prenatal vitamin supplements containing 0.8
      1.1 mg of folate, the prenatal vitamin supplements should be combined with 5 mg
      of folate.

PMID- 18053384
TI  - Women's Pain Experience Predicts Future Surgery for Pain Associated With
      Endometriosis.
AB  - OBJECTIVES: A previous randomized controlled trial from 1991 to 1993 comparing
      excision of endometriosis with sham surgery demonstrated no difference in
      reported pain after blinding between the excision and sham groups for one year.
      Overall, when both groups were considered, there was a significant reduction in
      pain one year postoperatively. This trial was done to determine the predictors of
      subsequent surgery. METHODS: The time to repeat surgery was the outcome of
      interest as a marker for significant pain. Survival analysis and log rank tests
      were performed to determine if the time to repeat surgery differed by group or by
      age, parity, original level of pain pre-operatively and stage of the disease.
      RESULTS: Only the reported measurement of pain prior to the initial trial was a
      significant covariate in the overall prediction of repeat surgery among all
      subjects. The overall repeat surgical operation rate was 48.3% in the sham
      surgery group and 51.7% in the excision group. The estimated relative risk for
      repeat surgery (excision vs. sham) was 1.42 (95% confidence intervals 0.539-
      3.75). CONCLUSION: Pain experience preoperatively was found to be an important
      predictor of subsequent surgical need. In this study, age, stage of disease, and
      excision of endometriosis were not associated with improvement in pain as
      measured by the time to repeat surgery.

PMID- 18053386
TI  - An investigation of embryo donation, informed consent, and research oversight in
      Canadian human embryonic stem cell research.
AB  - OBJECTIVES: To investigate compliance with applicable regulations by Canadian
      human embryonic stem cell (hESC) researchers and fertility clinics involved in
      providing embryos for their research, and to ascertain actual consent practices
      in the hESC research context. METHOD: Telephone interviews were conducted with
      all hESC researchers, and email interviews were conducted with fertility clinics
      that provide embryos to these researchers. Consent forms currently used for
      donation of embryos to hESC research were reviewed. Separate questionnaires were
      used for the researchers and clinics. RESULTS: Three of four clinics responded.
      Of the clinics that responded, each had provided embryos for hESC research to at
      least one of the researchers. Despite considerable policy attention given to hESC
      research, very few researchers and clinics are actually involved in the research
      in Canada. Only cryopreserved embryos are currently being used in hESC research,
      but one researcher has applied to use fresh embryos. Fertility clinics play a
      primary role in the consent process, and researchers have no contact with
      patients/donors. Although representations have been made in academic literature
      and the popular press suggesting a lack of compliance by Canadian hESC
      researchers, researchers and clinics report that they are in substantial
      compliance with applicable regulations. The researchers appear to be very
      conscious of the ethics of hESC research. In addition, they state that they are
      willing to follow the rules, but they are frustrated by the lack of regulatory
      clarity and by delays in the research oversight process. CONCLUSION: Empirical
      research on perceptions other stakeholders (donors, research ethics boards etc.)
      have of the hESC research process appears essential.

PMID- 18053387
TI  - Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid
      in combination with a multivitamin supplement for the prevention of neural tube
      defects and other congenital anomalies.
AB  - OBJECTIVE: To provide information regarding the use of folic acid in combination
      with a multivitamin supplement for the prevention of neural tube defects and
      other congenital anomalies, so that physicians, midwives, nurses, and other
      health care workers can assist in the education of women in the pre-conception
      phase of their health care. OPTION: Supplementation with folic acid and vitamins
      is problematic, since 50% of pregnancies are unplanned, and women's health status
      may not be optimal when they conceive. OUTCOMES: Folic acid in combination with a
      multivitamin supplement has been associated with a decrease in specific birth
      defects. EVIDENCE: Medline, PubMed, and Cochrane Database were searched for
      relevant English language articles published between 1985 and 2007. The previous
      Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of
      November 1993 and statements from the American College of Obstetrics and
      Gynecology and Canadian College of Medical Geneticists were also reviewed in
      developing this clinical practice guideline. VALUES: The quality of evidence was
      rated using the criteria described in the Report of the Canadian Task Force on
      Preventive Health Care. BENEFITS, HARMS, AND COSTS: Promoting the use of folic
      acid and a multivitamin supplement among women of reproductive age will reduce
      the incidence of birth defects. The costs are those of daily vitamin
      supplementation and eating a healthy diet. RECOMMENDATIONS: 1. Women in the
      reproductive age group should be advised about the benefits of folic acid in
      addition to a multivitamin supplement during wellness visits (birth control
      renewal, Pap testing, yearly examination) especially if pregnancy is
      contemplated. (III-A) 2. Women should be advised to maintain a healthy diet, as
      recommended in Eating Well With Canada's Food Guide (Health Canada). Foods
      containing excellent to good sources of folic acid are fortified grains, spinach,
      lentils, chick peas, asparagus, broccoli, peas, Brussels sprouts, corn, and
      oranges. However, it is unlikely that diet alone can provide levels similar to
      folate-multivitamin supplementation. (III-A) 3. Women taking a multivitamin
      containing folic acid should be advised not to take more than one daily dose of
      vitamin supplement, as indicated on the product label. (II-2-A) 4. Folic acid and
      multivitamin supplements should be widely available without financial or other
      barriers for women planning pregnancy to ensure the extra level of
      supplementation. (III-B) 5. Folic acid 5 mg supplementation will not mask vitamin
      B12 deficiency (pernicious anemia), and investigations (examination or
      laboratory) are not required prior to initiating supplementation. (II-2-A) 6. The
      recommended strategy to prevent recurrence of a congenital anomaly (anencephaly,
      myelomeningocele, meningocele, oral facial cleft, structural heart disease, limb
      defect, urinary tract anomaly, hydrocephalus) that has been reported to have a
      decreased incidence following preconception / first trimester folic acid +/-
      multivitamin oral supplementation is planned pregnancy +/- supplementation
      compliance. A folate-supplemented diet with additional daily supplementation of
      multivitamins with 5 mg folic acid should begin at least three months before
      conception and continue until 10 to 12 weeks post conception. From 12 weeks post
      conception and continuing throughout pregnancy and the postpartum period (4-6
      weeks or as long as breastfeeding continues), supplementation should consist of a
      multivitamin with folic acid (0.4-1.0 mg). (I-A) 7. The recommended strategy(ies)
      for primary prevention or to decrease the incidence of fetal congenital anomalies
      will include a number of options or treatment approaches depending on patient
      age, ethnicity, compliance, and genetic congenital anomaly risk status. OPTION A:
      Patients with no personal health risks, planned pregnancy, and good compliance
      require a good diet of folate-rich foods and daily supplementation with a
      multivitamin with folic acid (0.4-1.0 mg) for at least two to three months before
      conception and throughout pregnancy and the postpartum period (4-6 weeks and as
      long as breastfeeding continues). (II-2-A) OPTION B: Patients with health risks,
      including epilepsy, insulin dependent diabetes, obesity with BMI >35 kg/m2,
      family history of neural tube defect, belonging to a high-risk ethnic group
      (e.g., Sikh) require increased dietary intake of folate-rich foods and daily
      supplementation, with multivitamins with 5 mg folic acid, beginning at least
      three months before conception and continuing until 10 to 12 weeks post
      conception. From 12 weeks post-conception and continuing throughout pregnancy and
      the postpartum period (4-6 weeks or as long as breastfeeding continues),
      supplementation should consist of a multivitamin with folic acid (0.4-1.0 mg).
      (II-2-A) OPTION C: Patients who have a history of poor compliance with
      medications and additional lifestyle issues of variable diet, no consistent birth
      control, and possible teratogenic substance use (alcohol, tobacco, recreational
      non-prescription drugs) require counselling about the prevention of birth defects
      and health problems with folic acid and multivitamin supplementation. The higher
      dose folic acid strategy (5 mg) with multivitamin should be used, as it may
      obtain a more adequate serum red blood cell folate level with irregular vitamin /
      folic acid intake but with a minimal additional health risk. (III-B) 8. The
      Canadian Federal Government could consider an evaluation process for the
      benefit/risk of increasing the level of national folic acid flour fortification
      to 300 mg/100 g (present level 140 mg/100 g). (III-B) 9. The Canadian Federal
      Government could consider an evaluation process for the benefit/risk of
      additional flour fortification with multivitamins other than folic acid. (III-B)
      10. The Society of Obstetricians and Gynaecologists of Canada will explore the
      possibility of a Canadian Consensus conference on the use of folic acid and
      multivitamins for the primary prevention of specific congenital anomalies. The
      conference would include Health Canada/Congenital Anomalies Surveillance,
      Canadian College of Medical Geneticists, Canadian Paediatric Society, Motherisk,
      and pharmaceutical industry representatives. VALIDATION: This is a revision of a
      previous guideline and information from other consensus reviews from medical and
      government publications has been used. SPONSOR: The Society of Obstetricians and
      Gynaecologists of Canada.

PMID- 18053389
TI  - Multidisciplinarity, interdisciplinarity, and transdisciplinarity in health
      research, services, education and policy: 2. Promotors, barriers, and strategies
      of enhancement.
AB  - BACKGROUND/PURPOSE: Multidisciplinary, interdisciplinary and transdisciplinary
      teams are increasingly encouraged in health research, services, education and
      policy. This paper is the second in a series. The first discussed the
      definitions, objectives, and evidence of effectiveness of multiple disciplinary
      teamwork. This paper continues to examine the promotors, barriers, and ways to
      enhance such teamwork. METHODS: The paper is a literature review based on Google
      and MEDLINE (1982-2007) searches. "Multidisciplinarity", "interdisciplinarity",
      "transdisciplinarity" and "definition" were used as keywords to identify the
      pertinent literature. RESULTS: The promotors of teamwork success include: good
      selection of team members, good team leaders, maturity and flexibility of team
      members, personal commitment, physical proximity of team members, the Internet
      and email as a supporting platform, incentives, institutional support and changes
      in the workplace, a common goal and shared vision, clarity and rotation of roles,
      communication, and constructive comments among team members. The barriers, in
      general, reflect the situation in which the promotors are lacking. They include:
      poor selection of the disciplines and team members, poor process of team
      functioning, lack of proper measures to evaluate success of interdisciplinary
      work, lack of guidelines for multiple authorship in research publications,
      language problems, insufficient time or funding for the project, institutional
      constraints, discipline conflicts, team conflicts, lack of communication between
      disciplines, and unequal power among disciplines. CONCLUSION: Not every health
      project needs to involve multiple disciplines. Several questions can help in
      deciding whether a multiple disciplinary approach is required. If multiple
      disciplinarity is called for, eight strategies to enhance multiple disciplinary
      teamwork are proposed. They can be summarised in the acronym TEAMWORK - Team,
      Enthusiasm, Accessibility, Motivation, Workplace, Objectives, Role, Kinship.

PMID- 18053390
TI  - Clinical predictors of facial nerve outcome after translabyrinthine resection of
      acoustic neuromas.
AB  - PURPOSE: The translabyrinthine approach to acoustic neuroma resection offers
      excellent exposure for facial nerve dissection with 95% preservation of anatomic
      continuity. Acceptable outcome in facial asymptomatic patients is reported at 64
      90%, but transient postoperative deterioration often occurs. The objective of
      this study was to identify preoperative clinical presentation and intraoperative
      surgical findings that predispose patients to facial nerve dysfunction after
      acoustic neuroma surgery. METHODS: The charts of 128 consecutive
      translabyrinthine patients were examined retrospectively to identify new clinical
      and intraoperative predictors of facial nerve outcome. Postoperative evaluation
      of patients to normal function or mild asymmetry upon close inspection (House
      Brackmann grades of I or II) was defined as an acceptable outcome, with obvious
      asymmetry to no movement (grades III to VI) defined as unacceptable.
      Intraoperative nerve stimulation was performed in all cases, and clinical grading
      was performed by a single neurosurgeon in all cases. RESULTS: Among patients with
      no preoperative facial nerve deficit, 87% had an acceptable result. Small size (P
      < 0.01) and low intraoperative nerve stimulation of < 0.10 mA (P< 0.01) were
      reaffirmed as predictive of functional nerve preservation. Additionally,
      preoperative tinnitus (P = 0.03), short duration of hearing loss (P< 0. 01), and
      lack of subjective tumour adherence to the facial nerve (P = 0.02) were
      independently correlated with positive outcome. CONCLUSIONS: Our experience with
      the translabyrinthine approach reveals the previously unestablished associations
      of facial nerve outcome to include presence of tinnitus and duration of
      hypoacusis. Independent predictors of tumour size and nerve stimulation
      thresholds were reaffirmed, and the subjective description of tumour adherence to
      the facial nerve making dissection more difficult appears to be important.

PMID- 18053391
TI  - Serum IgA1 from IgA nephropathy patients induces apoptosis in podocytes through
      direct and indirect pathways.
AB  - PURPOSE: To investigate apoptosis of podocytes induced by IgA1 isolated from IgA
      nephropathy (IgAN) patients through direct and indirect pathways. METHODS:
      Jacalin affinity chromatography and Sephacryl S-200 molecular sieve
      chromatography were used to isolate IgA1 from blood of IgAN patients made as
      aggregated IgA1 (aIgA1). Podocytes were incubated with aIgA1 or special treated
      medium from mesangial cells after co-incubation with aIgA1 from IgAN patients.
      Apoptosis of podocytes was assessed by TUNEL staining and flow cytometry. Real
      time PCR was used to detect the mRNA expression of Bcl-2, Bax, Fas and Fas-L.
      RESULTS: AIgA1 from IgAN patients induced more apoptosis of podocytes by both
      time and concentration-dependent patterns than control (30.5+/-5.4% vs 20.5+/
      4.5, respectively, P < 0.05). The percentage of apoptotic podocytes exposed to
      treated medium was higher than control (28.5+/-5.9 % vs 20.5+/-4.5%,
      respectively, P < 0.05). The level of normalized Fas mRNA expression in podocytes
      exposed to aIgA1 was 2.4-fold higher than control (P < 0.05), while the level in
      podocytes exposed with treated medium was 1.89-fold higher than control (P <
      0.05), and the level of normalized Bcl-2 mRNA expression in this group was 72%
      lower than control (P < 0.05) CONCLUSION: IgA1 from IgAN patients may induce
      apoptosis of podocytes through direct and indirect pathways. IgA1 may accelerate
      progression of IgAN by inducing apoptosis of podocytes.

PMID- 18053392
TI  - Evaluation of in vivo and in vitro biological activity of a Vibrio cholerae 01
      hemolysin.
AB  - PURPOSE: To evaluate the hemolysin effect by ileal loop model produced by Vibrio
      cholerae O1 strains, compared with the cellular lysis or cytotoxic activity (CA)
      observed in cell culture. METHOD: We studied nine V. cholerae O1 strains,
      obtained during the Mexican outbreak of cholera (1990-1993), which had CA in Vero
      and CHO cells. Hemolysin was monitored with the hemolysis test. Titers of CA were
      calculated by CD50, and the association between CA and cholera toxin (CT)
      production was discarded by means of neutralization tests using an anti-CT
      polyclonal antibody. The CT production was measured with ELISA test. The LAL
      assay was performed in order to study relationships between the CA and bacterial
      lipopolysaccharide. Strains with CA were evaluated in rabbit and rat ileal loop
      models; hemorrhagic fluid was also measured. Tissues from ileal loop were
      included in paraffin to detect intestinal epithelial damage. RESULTS: The
      hemolysin CA was not neutralized with the anti-CT polyclonal antibody. However,
      the associated factor of CA was heat labile. CA in cell cultures was not related
      to the bacterial lipopolysaccharide. The ileal loop test exhibited the presence
      of hemorrhagic tissue with inflammation. CONCLUSION: The V. cholerae O1 strains
      isolated were able to secrete hemolysin which, in turn, caused CA in cell
      cultures and produced the hemorrhagic and inflammatory effects observed in the
      ileal loop of rabbit and rat models.

PMID- 18053393
TI  - Impact of beta-blocker treatment and nutritional status on glycemic response
      during exercise in patients with type 2 diabetes.
AB  - PURPOSE: Most individuals with type 2 diabetes are affected by hypertension and
      thus have higher risk of cardiac complications. In addition to behavioural
      modifications, such as healthy food choices and regular physical activity, beta
      blocker treatment may be considered to reduce morbidity and mortality, especially
      after a cardiovascular event. However, this medication is generally associated
      with a deleterious impact on glucose metabolism. The objective of the study was
      to assess the impact of beta-blocker treatment on glucose response during
      exercise in patients with type 2 diabetes, free of cardiovascular complications.
      METHODS: Ten sedentary men, treated with diet and/or hypoglycemic agents have
      performed four exercise sessions at 60% of their V O2peak, in the fasted state or
      2 hours following a standardized breakfast, with and without beta-blockers
      (atenolol 100 mg id for five consecutive days). Blood samples were drawn during
      the resting period, at 15-min intervals during the exercise session and during
      the recovery period. RESULTS: A reduction of blood glucose levels was observed
      following the exercise session in the postprandial state (48% and 44% reduction
      with and without beta-blockers respectively; P < 0.001). One hour of exercise
      performed in the fasted state had a minimal impact on glucose and insulin levels,
      whether with or without beta-blockers. beta-blocker treatment was not associated
      with increased baseline blood glucose or insulin levels in the fasted or the
      postprandial situation. CONCLUSION: Dietary status has a more important impact on
      plasma glucose and insulin modulation than short-term use of beta-blockers.

PMID- 18053394
TI  - Does the energy expenditure status in obstructive sleep apnea favour a positive
      energy balance?
AB  - PURPOSE: The effect of the obstructive sleep apnea syndrome on energy expenditure
      is controversial. The objective of this study was to assess the relationship
      between 24-hr energy expenditure or sleeping metabolic rate and features of the
      obstructive sleep apnea. METHODS: Twenty-four apneic men took part in this cross
      sectional study and were classified in quartiles of nocturnal desaturation
      severity, i.e. of percentage total sleep time with SaO2 < 90% determined with
      polysomnography. 24-hr energy expenditure and sleeping metabolic rate were
      measured with a whole body indirect calorimetry (respiratory chamber), and body
      composition by hydrodensitometry. During the stay in the respiratory chamber,
      urine was collected to assess catecholamine concentration and percentage
      recording time with SaO2 < 90% (%TRT SaO2 < 90%) was measured with nocturnal
      oximetry. RESULTS: Mean fat free mass and fat mass were greater in quartile 4
      than in quartile 1 (P < 0.05). %TRT SaO2 < 90% was higher in quartile 4 than in
      other quartiles (P < 0.0001). 24-hr energy expenditure and sleeping metabolic
      rate were similar among quartiles. However, when expressed on a per kg body
      weight basis (kcal/kg), these variables were negatively correlated with the %TRT
      SaO2 < 90% in the whole group (r = -0.46 and -0.48, respectively, P < 0.05). %TRT
      SaO2 < 90% was found to be a predictor of sleeping metabolic rate which
      explained, together with fat mass and fat free mass, 86% of this variance (P <
      0.05). CONCLUSION: In apneic men energy expenditure relative to body weight
      decreases with increasing severity of oxygen desaturation which could favour a
      positive energy balance.

PMID- 18053395
TI  - CSCI/RCPSC Henry Friesen lecture: the past and the future of neurogenetics.

PMID- 18053396
TI  - Influence of a platelet concentrate on prosthetic bone ingrowth in a rabbit
      model.
AB  - Recent studies have shown that an increase in bone ingrowth by addition of
      osteogenic growth factors can reduce micro motion and gross implant motion and
      contribute to joint implant stability through osseointegration. Platelet-rich
      plasma (PRP) has the potential to provide growth factors that may be conducive to
      osteointegration at the bone-implant interface. This study analyzed the influence
      of PRP on bone ingrowth upon a beaded metal implant in distal femurs of 22
      rabbits. Rabbit limbs were randomly assigned to receive an implant plus PRP or
      plain implant. Half of the specimens were randomly assigned to a 2-week group (n
      = 20) or a 5-week group (n = 20). Histologic and histomorphometric comparison
      between implant alone and implant plus PRP, at 2 and 5 weeks, was performed. In
      both the 2- and 5-week comparisons, there was no statistical difference (p > .05)
      in bone ingrowth between the control and PRP group, despite a slight increase in
      trabecular bone growth in PRP groups. This study suggests that PRP is not a major
      contributing factor to bone ingrowth at the bone-implant interface. This supports
      growing evidence in the literature that PRP can lead to variable bone growth
      stimulation in vivo.

PMID- 18053397
TI  - Primary posterior cruciate-retaining total knee arthroplasty: a comparison of
      American and Japanese cohorts.
AB  - Excessive polyethylene wear is recognized as one of the most important factors
      affecting the durability of total knee arthroplasty; however, bearing surface
      wear is a multifactorial problem. The purpose of this study was to identify
      factors for polyethylene wear and failure in primary posterior cruciate-retaining
      (PCR) total knee arthroplasty (TKA) in two disparate cohorts (American and
      Japanese). Seventy-three total knee arthroplasty operations were performed on 48
      Japanese patients, and 76 on 63 American patients with noninflammatory
      arthritides. All patients were evaluated clinically and radiographically using a
      total joint arthroplasty database. Age, weight, diagnosis, Knee Society patient
      category, prosthesis size, insert thickness, alignment, polyethylene wear,
      osteolysis, Knee Society knee score, Knee Society pain score, and radiographic
      and clinical survivorship were evaluated. Seventy-three Japanese TKAs were
      followed for a mean of 6.6 years (range, 2.0-10.6). Three (4.1%) Japanese
      patients required revision. Seventy-six American TKAs were followed for a mean of
      9 years (range, 2-10.2). Two (2.6%) American patients required revision. The
      American patients were significantly older, heavier, male predominant, and
      required larger size implants. The Japanese patients were significantly more
      female predominant and had a significantly less postoperative arc of motion. Knee
      Society knee and pain scores, survivorship, average total polyethylene wear, and
      annual wear rates were not different among the two cohorts. PCR TKA had similar
      survivorship in disparate cohorts of Japanese and American total knee
      arthroplasty patients despite smaller stature patients in the Japanese cohort.
      Cultural, gender-specific, and morphologic differences need to be considered for
      knee implant design. However, survivorship and polyethylene wear rates appear to
      be independent of these factors in disparate populations.

PMID- 18053398
TI  - Does knee position at the time of tourniquet inflation affect knee range of
      motion?
AB  - Pneumatic tourniquets about the thigh are commonly employed in lower extremity
      orthopaedic surgery to maintain a bloodless operative field. The purpose of this
      study was to determine whether the position of the knee at the time of tourniquet
      inflation has an impact on knee range of motion (ROM). Passive ROM of the knees
      of 30 patients was measured with the tourniquet deflated, with the tourniquet
      inflated while the knees were in extension, and with the tourniquet inflated
      while the knees were in flexion. The average knee ROM with a deflated tourniquet
      was 143.0 degrees with a standard deviation of 8.1 degrees (range, 125 degrees 
      160 degrees ). When the tourniquet was inflated with the knees in extension, the
      average knee ROM was 143.0 degrees with a standard deviation of 7.8 degrees
      (range, 125 degrees -159 degrees ). When the tourniquet was inflated with the
      knees in flexion, the average knee ROM was 143.7 degrees with a standard
      deviation of 7.8 degrees (range, 124 degrees -160 degrees ). There was a
      statistically significant difference between the ROM of knees with tourniquet
      inflation in flexion versus extension (p = .0011.) Although there was a
      statistical difference, it was concluded that a difference of approximately 1
      degrees in knee ROM is not clinically relevant.

PMID- 18053399
TI  - Surgical correction of spinal deformities following spinal cord injury occurring
      in childhood.
AB  - This article reports on the surgical treatment of 14 consecutive patients with
      paralytic spinal deformities secondary to spinal cord injury occurring in
      childhood. Eleven patients underwent a posterior spinal fusion and three patients
      underwent a combined anterior and posterior spinal arthrodesis. Luque rods were
      used in all but one patient. The spinal fusion extended to the sacrum in 10
      patients. No patient developed postoperative wound infections or medical
      complications. Four patients (28.6%) who underwent initially a posterior spinal
      arthrodesis developed pseudarthrosis. This was treated successfully by a combined
      anterior and posterior spinal fusion in two patients. The remaining patients
      underwent a revision posterior spinal fusion with recurrence of the nonunion in
      one patient. A combined anterior and posterior spinal arthrodesis could be
      considered the treatment of choice for patients with severe deformities who can
      tolerate anterior surgery. If pseudarthrosis develops following posterior spinal
      fusion, this can be best treated by a combined anterior and posterior revision
      procedure with instrumentation.

PMID- 18053400
TI  - Role of the peroneal tendons and superior peroneal retinaculum as static
      stabilizers of the ankle.
AB  - The role of the peroneal tendons as static stabilizers of the ankle is poorly
      understood. Anterior-posterior displacement of the talus was evaluated in eight
      fresh-frozen cadaveric ankle joints. With the distal tibia stabilized, loads of
      150 N were applied to the talus in the anterior direction while the ankle was
      held in neutral. All tests were initially performed on intact specimens. Loads
      were reapplied after sequential sectioning of the peroneal tendons and superior
      peroneal retinaculum and then the anterior talofibular ligament. When compared
      with intact ankles, releasing the peroneal tendons caused an average increase of
      15% displacement (0.90 mm, p < .05). Adding the release of the anterior
      talofibular ligament increased the anterior displacement an additional 16% (1.35
      mm, p < .05) for a combined anterior laxity of 34% (2.25 mm, p < .05). The data
      suggest that the peroneal tendons along with the superior peroneal retinaculum
      provide static resistance to anterior talar displacement with the ankle in
      neutral. This may contribute to the overall stability of the lateral ankle not
      previously recognized.

PMID- 18053401
TI  - Sensory communication of the median and ulnar nerves in the palm.
AB  - A communicating branch between the median and superficial ulnar nerve in the palm
      of the hand has been described, but its relationship to the cutaneous anatomy of
      the hand has had little emphasis. Fifty preserved cadaveric hands were dissected.
      A communicating branch was found in 37 of 50 specimens. In 34 specimens, the
      connecting branch proceeded from the ulnar nerve to enter the median nerve
      distally; in three specimens it proceeded from the median nerve to reach the
      ulnar nerve distally. This study describes the communicating branch in relation
      to the distal crease of the wrist with the axis of the third webspace and fifth
      ray as the radial and ulnar borders, respectively. This study may aid surgeons in
      determining the likelihood of injury in trauma or during various surgical
      procedures.

PMID- 18053402
TI  - Cluster of Mycobacterium fortuitum prosthetic joint infections.
AB  - Mycobacterium fortuitum is a member of the rapidly growing nontuberculous
      mycobacteria. Although mortality is rare from M. fortuitum, morbidity depends on
      the localized site of infection. M. fortuitum is ubiquitous in the environment
      and has been reported to cause infections of prosthetic devices. There have been
      seven previously reported cases of prosthetic joint infections due to M.
      fortuitum. This article presents three additional cases of postoperative joint
      infections due to M. fortuitum. All three cases were confirmed to be genetically
      indistinguishable by pulse-field gel electrophoresis. Awareness of its importance
      is especially noteworthy in the realm of ongoing antibiotic resistance.

PMID- 18053403
TI  - Infraclavicular brachial plexopathy secondary to coracoid osteoid osteoma.
AB  - Coracoid osteoid osteomas are rare. This case report presents two patients with
      coracoid osteoid osteomas who developed neurologic sequelae of the
      infraclavicular brachial plexus (namely, musculocutaneous neuropathy in one
      patient with an anterior lesion, and suprascapular neuropathy in the other
      patient with a more posterior lesion). The neuropathy was due to soft tissue
      edema, which surrounded the bony lesion and was apparent on MRI. Surgical
      resection of the bony lesion in both cases produced excellent outcomes at long
      term follow-up.

PMID- 18053404
TI  - Hip incision planning for free vascularized fibular grafting of the proximal
      femur: a handy tip.
AB  - Free vascularized fibula graft surgery has been shown to be successful in the
      treatment of osteonecrosis of the femoral head. Refinements in the surgical
      technique have greatly decreased patient morbidity and overall surgical time.
      Careful placement of the hip incision is one such refinement. Specific bony
      landmarks to map out the location of the incision and a simple technique for
      incision placement are described. An accurately placed 10- to 15-cm incision will
      allow access to both the proximal femur and the ascending branch of the lateral
      femoral circumflex artery and veins.

PMID- 18053405
TI  - Re: Ewing's sarcoma of the hip presenting as a benign cyst lesion,
      Papagelopoulos, P.J., Mavrogenis, A.F., Benetos, I.S., Papaparaskeva, K.,
      Galanis, E.C., Soucacos, P.N., JSOA 16(2):84-88, 2007.

PMID- 18053408
TI  - Image-guided analyses reveal that non-CD4 splenocytes contribute to CD4+ T cell
      mediated inflammation leading to islet destruction by altering their local
      function and not systemic trafficking patterns.
AB  - Recruitment of CD4(+) T cells into islets is a critical component of islet
      inflammation (insulitis) leading to type 1 diabetes; therefore, determining if
      conditions used to treat diabetes change their trafficking patterns is relevant
      to the outcome. Cotransfer of CD4(+)BDC2.5 (BDC) cells with non-CD4 splenocytes
      obtained from newly diabetic NOD mice, but not when they are transferred alone,
      induces accelerated diabetes. It is unclear whether these splenocytes affect
      diabetes development by altering the systemic and/or local trafficking and
      proliferation patterns of BDC cells in target and nontarget tissues. To address
      these questions, we developed an animal model to visualize BDC cell trafficking
      and proliferation using whole-body in vivo bioluminescence imaging and used the
      images to direct tissue sampling for further analyses of the cell distribution
      within tissues. The whole-body, or macroscopic, trafficking patterns were not
      dramatically altered in both groups of recipient mice. However, the local
      patterns of cell distribution were distinct, which led to invasive insulitis only
      in cotransferred mice with an increased number of islet-infiltrating CD11b(+) and
      CD11c(+) cells. Taken together, the non-CD4 splenocytes act locally by promoting
      invasive insulitis without altering the systemic trafficking patterns or
      proliferation of BDC cells and thus contributing to diabetes by altering the
      localization within the tissue.

PMID- 18053410
TI  - Noninvasive detection of matrix metalloproteinase activity in vivo using a novel
      magnetic resonance imaging contrast agent with a solubility switch.
AB  - We have developed novel proteinase-modulated contrast agents (PCAs) to detect the
      activity of proteinases in vivo using magnetic resonance imaging. The PCAs are
      based on the concept of a solubility switch, from hydrophilic to hydrophobic,
      that significantly modifies the pharmacokinetic properties of the agent as
      revealed by the slow efflux kinetics from the activity site. Our compound PCA7
      switch detects the activity of the secreted matrix-degrading proteinase matrix
      metalloproteinase 7 (MMP-7) in living, tumor-bearing mice. Control experiments
      were performed using an agent that was not cleaved by MMP-7 (PCA7-scrambled), an
      agent that could be cleaved by MMP-7 but lacked the solubility switch (PCA7-B),
      and a standard contrast agent (gadolinium-diethylenetriaminepentaacetic acid).
      PCA7-switch detected a reduction in MMP-7 activity in tumor-bearing mice treated
      with a synthetic MMP inhibitor, demonstrating its effectiveness in noninvasive
      functional imaging of proteolytic activity in vivo.

PMID- 18053409
TI  - Tailoring the size distribution of ultrasound contrast agents: possible method
      for improving sensitivity in molecular imaging.
AB  - Encapsulated microbubble contrast agents incorporating an adhesion ligand in the
      microbubble shell are used for molecular imaging with ultrasound. Currently
      available microbubble agents are produced with techniques that result in a large
      size variance. Detection of these contrast agents depends on properties related
      to the microbubble diameter such as resonant frequency, and current ultrasound
      imaging systems have bandwidth limits that reduce their sensitivity to a
      polydisperse contrast agent population. For ultrasonic molecular imaging, in
      which only a limited number of targeted contrast agents may be retained at the
      site of pathology, it is important to optimize the sensitivity of the imaging
      system to the entire population of contrast agent. This article presents contrast
      agents with a narrow size distribution that are targeted for molecular imaging
      applications. The production of a functionalized, lipid-encapsulated, microbubble
      contrast agent with a monodisperse population is demonstrated, and we evaluate
      parameters that influence the size distribution and demonstrate initial acoustic
      testing.

PMID- 18053411
TI  - HSP70-inducible hNIS-IRES-eGFP reporter imaging: response to heat shock.
AB  - A retroviral vector pQHSP70/hNIS-IRES-eGFP (pQHNIG70) was constructed containing
      the hNIS-IRES-eGFP dual-reporter genes under the control of an inducible human
      heat shock protein (HSP)70 promoter and RG2-pQHSP70/hNIS-IRES-eGFP (RG2-pQHNIG70)
      transduced cells were generated. Heat-induced expression of both reporter genes
      in RG2-pQHNIG70 cells was validated by enhanced green fluorescent protein (eGFP)
      fluorescence-activated cell sorter, in vitro radiotracer assays, and immunoblot
      and immunocytochemistry. A 2.2- to 6.1-fold ((131)I(-)), a 6.1- to 14.4-fold
      ((99m)TcO(4)(-)), and a 5.1- to 39-fold (fluorescence) increase above baseline
      was observed in response to graded hyperthermia (39-43 degrees C). Increases in
      eGFP fluorescence and radiotracer uptake were first noted at 6 hours, reached a
      maximum at 24 hours, and fell toward baseline at 72 hours. A stable ratio of
      radiotracer uptake to eGFP fluorescence and to heat shock protein (HSP)70 protein
      was demonstrated over a wide range of expression levels, induced by different
      levels of heating. We also demonstrate that the local application of heat on RG2
      pQHNIG70 xenografts can effectively induce hNIS and eGFP gene expression in vivo
      and that this expression can be efficiently visualized by fluorescence,
      scintigraphic, and micro-positron emission tomography imaging. Endogenous HSP70
      protein and reporter expression was confirmed by postmortem tissue evaluations
      (immunoblot and immunohistochemistry). The pQHNIG70 reporter system can be used
      to study stress and drug responses in transduced cells and tissues.

PMID- 18053412
TI  - Targeting phosphatidylserine on apoptotic cells with phages and peptides selected
      from a bacteriophage display library.
AB  - Phosphatidylserine (PS) is a well-characterized biomarker for apoptosis. Ligands
      that bind to PS can be used for noninvasive imaging of therapy-induced cell
      death, particularly apoptosis. In this study, we screened a random 12-mer peptide
      phage library on liposomes prepared from PS. One clone displaying the peptide
      SVSVGMKPSPRP (designated as PS3-10) bound to PS approximately 4-fold better than
      its binding to phosphatidylcholine and 18-fold better than to bovine serum
      albumin in a solid-phase binding assay. In addition, the binding of the
      corresponding PS3-10 peptide to PS was significantly higher than that of a
      scrambled peptide. PS3-10 phages, but not a control 4-2-2 phage, bound to aged
      red blood cells that had PS exposed on their surface. Binding of PS3-10 phages
      and PS3-10 peptide to TRAIL-induced apoptotic DLD1 cells was 3.2 and 5.4 times
      higher than their binding to untreated viable cells, respectively. Significantly,
      immunohistochemical staining confirmed selective binding of PS3-10 phages to
      apoptotic cells. Our data suggest that panning of phage display libraries may
      allow the selection of suitable peptide ligands for apoptotic cells and that PS3
      10 peptide may serve as a template for further development of molecular probes
      for in vitro and in vivo imaging of apoptosis.

PMID- 18053413
TI  - Signaling can be uncoupled from imaging of the somatostatin receptor type 2.
AB  - Endogenous and exogenous somatostatin receptors are commonly targeted for imaging
      using radiopharmaceutical analogues of somatostatin. Ligand binding activates
      receptor-mediated signaling. We assessed whether somatostatin receptor type 2A
      (SSTR2A) imaging can be uncoupled from signal transduction. In both human
      fibrosarcoma (HT1080) and human embryonic kidney (HEK293) cells, reverse
      transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay
      found similar levels of expression of hemagglutinin A tagged SSTR2A (HA-SSTR2A)
      or the same fusion protein with a deletion of the C-terminus beyond amino acid
      314 (HA-SSTR2Delta314). Scatchard analysis demonstrated similar degrees of ligand
      binding by the wild-type or mutant receptor to (111)In-octreotide in both cell
      pairs. Cyclic guanosine monophosphate (cGMP) production and inhibition of
      forskolin-induced cylic adenosine monophosphate (cAMP) production were evaluated
      at the signaling level, and growth inhibition was evaluated at the cellular level
      before and after stimulation. Unlike wild-type receptor, HA-SSTR2Delta314 was
      deficient in inhibiting forskolin-induced cAMP production (p < .05) and in
      inciting cGMP (p < .05) production; furthermore, at the cellular level, HA
      SSTR2Delta314 was deficient in inhibiting cell proliferation (p < .05). Yet
      tumors expressing HA-SSTR2Delta314 could be imaged in vivo. Thus, in vivo imaging
      of SSTR2 can be uncoupled from cAMP and cGMP signaling as well as growth
      inhibition.

PMID- 18053416
TI  - Nitric oxide: what a vascular surgeon needs to know.
AB  - Atherosclerosis in the form of peripheral arterial disease results in significant
      morbidity and mortality. Surgical treatment options for peripheral arterial
      disease include angioplasty with and without stenting, endarterectomy, and bypass
      grafting. Unfortunately, all of these procedures injure the vascular endothelium,
      which impairs its ability to produce nitric oxide (NO) and ultimately leads to
      neointimal hyperplasia and restenosis. To improve on current patency rates after
      vascular procedures, investigators are engaged in research to improve the
      bioavailability of NO at the site of vascular injury in an attempt to reduce the
      risk of thrombosis and restenosis after successful revascularization. This
      article reviews some of the previous research that has aimed to improve NO
      bioavailability after vascular procedures whether through systemic or local
      delivery, as well as to describe some of the NO-releasing products that are
      currently undergoing study for use in clinical practice.

PMID- 18053417
TI  - Mitochondriopathy of peripheral arterial disease.
AB  - The signs and symptoms of peripheral arterial occlusive disease (PAD), including
      claudication, rest pain, and tissue loss, are consequences of compromised
      bioenergetics and oxidative tissue injury within the affected lower extremities.
      Compromised bioenergetics is the result of a combination of low blood flow
      through diseased arteries and diminished adenosine triphosphate production by
      dysfunctional mitochondria. The tissue injury appears to be secondary to
      increased production of reactive oxygen species by dysfunctional mitochondria and
      by inflammation, in association with ischemia and ischemia/reperfusion. In this
      review, we present the current histomorphologic, physiologic, and biochemical
      evidence defining the nature of this mitochondriopathy and discuss its
      contribution to the pathogenesis and clinical manifestations of PAD.

PMID- 18053418
TI  - Regulation of vascular smooth muscle cell growth by survivin.
AB  - The inhibitor of apoptosis protein survivin has long been of interest in the
      cancer literature for its role in both the regulation of cell proliferation and
      the inhibition of apoptosis. A growing body of literature has implicated survivin
      in the maladaptive pathways following vascular injury and, in particular, in the
      growth of vascular smooth muscle cells that comprise the hyperplastic neointimal
      lesions that characterize midterm vein bypass graft failure and restenosis
      following angioplasty and stenting. This review focuses on the emerging role of
      survivin in the regulation of smooth muscle cell growth and its implications for
      the prevention of restenosis following revascularization procedures. The
      expression, regulation, and function of survivin are addressed, as well as the
      current state of understanding regarding the effects of survivin inhibition in
      vitro and in vivo.

PMID- 18053419
TI  - Chemokines and diabetic wound healing.
AB  - Chemokines are critical for white blood cell recruitment to injured tissues and
      play an important role in normal wound healing processes. In contrast, impaired
      wound healing in diabetic patients is accompanied by decreased early inflammatory
      cell infiltration but persistence of neutrophils and macrophages in the chronic,
      nonhealing wounds. These changes in inflammatory cell recruitment occur in
      conjunction with alterations in chemokine and growth factor expression. In
      addition to leukocyte trafficking, many different cell types, including
      endothelial cells, fibroblasts, and keratinocytes, produce and respond to
      chemokines, and these interactions are altered in diabetic wounds. Thus, the
      chemokine system may have both direct and inflammatory-mediated effects on many
      different aspects of diabetic wound healing. The potential roles of chemokines
      and inflammatory or immune cells in nonhealing diabetic wounds, including
      impairments in growth factor expression, angiogenesis, extracellular matrix
      formation, and reepithelialization, are examined.

PMID- 18053420
TI  - Optimal prosthetic graft design for small diameter vascular grafts.
AB  - Autogenous vein and arterial grafts, such as great saphenous veins and internal
      mammary and radial arteries, remain the gold standard conduits for vascular
      reconstruction. Expanded polytetrafluoroethylene (PTFE) grafts, which exhibit
      little inflammatory and thrombogenic reactivity, are the most commonly used
      material of choice for small diameter vascular grafts when autogenous grafts are
      not available. Several modifications of the basic graft have been attempted to
      enhance graft healing of expanded PTFE grafts, and little but definite
      experimental and clinical improvement has been achieved so far. The technique of
      vascular tissue engineering, in combination with stem cell research, may hold the
      key for the creation of a practical and successful small diameter prosthetic
      graft.

PMID- 18053421
TI  - Medical therapy approach for treating abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is a common and deadly problem. The aortic
      diameter increases in association with a complex remodeling process that includes
      changes in the structure and content of key proteins, elastin and collagen. As
      these changes occur, the tissue mechanical properties also change. The natural
      history of AAA is progressive enlargement to a point of mechanical tissue
      failure, typically followed by death. Currently, the marker used to predict the
      risk of impending rupture is the largest transverse diameter. After reaching a
      diameter threshold of 5.5 cm, the aneurysm is surgically repaired. This criterion
      does not consider any patient-specific information or the known heterogeneity of
      the aneurysm that may, in some cases, lead to rupture before the aneurysm reaches
      the standard intervention threshold. Conversely, in many patients, continued
      observation beyond this threshold is safe. Although no medical treatment is yet
      approved, doxycycline has been shown to greatly reduce aortic aneurysm growth in
      animal models and has been shown to slow growth in several small clinical trials.
      Although larger prospective randomized trials are needed, one unknown is what
      effect doxycycline has on the structural integrity of the aortic wall. That is,
      does slowed aneurysm growth by doxycycline treatments, in fact, prevent rupture,
      or does the wall continue to weaken and the aneurysm instead ruptures at a
      smaller diameter? Research has begun to answer these questions before a large
      clinical trial begins.

PMID- 18053422
TI  - Plasmin and matrix metalloproteinase system in deep venous thrombosis resolution.
AB  - Deep venous thrombosis (DVT) is a common event in hospitalized medical and
      surgical patients. Outside of anticoagulation, few good options exist for
      decreasing the vein wall damage that results after natural thrombolysis. DVT
      resolution is complex and involves chemokines, leukocytes, and native vein wall
      cells. Herein some aspects of DVT resolution related to the intersection of
      inflammation, the plasminogen and matrix metalloproteinase systems, and their
      respective inhibitors are reviewed. Ultimately, better knowledge of these natural
      thrombolytic systems may allow local, directed, and specific acceleration of DVT
      resolution and decreased vein wall damage.

PMID- 18053423
TI  - Direct thrombin inhibitors: alternatives to heparin.
AB  - After more than 70 years of effective clinical use, heparin remains the most
      common anticoagulant in use and one of the most commonly prescribed drugs to
      hospitalized patients. However, the biologic variability and immunogenicity limit
      its utility. With increasing volumes of vascular intervention and an aging
      population, an increase in the need for anticoagulation can be anticipated. This
      article reviews current viable options and barriers to the use of heparin.

PMID- 18053424
TI  - Theory, technique, and practice of magnetic resonance angiography.
AB  - Magnetic resonance angiography (MRA) is now a widely accepted technique used to
      characterize vascular pathology such as stenosis, dissection, fistula, and
      aneurysms. Magnetic resonance techniques are increasingly driving clinical
      decision making by vascular physicians. The physics behind MRA can contribute to
      the general understanding and interpretation of the anatomic images. We seek to
      provide a window into how magnetic resonance images are generated, which
      techniques may be employed, and the potential advantages and limitations of
      various techniques and to discuss the future role MRA may have for the vascular
      physician.

PMID- 18053425
TI  - Endothelial progenitor cells: a primer for vascular surgeons.
AB  - Endothelial progenitor cells (EPCs) participate in vascular healing during both
      acute injury and chronic disease. The quantity and quality of circulating EPCs
      correlate inversely with the severity of vascular disease, such that reduced
      number and/or function of EPCs are significant independent risk factors for
      impaired healing capacity, dysfunctional endothelium, and progression of
      atherosclerosis and vascular disease. EPC therapy assists healing of cardiac and
      limb ischemia and has great potential for improving the quality of life and
      longevity of patients with severe cardiovascular and peripheral vascular disease
      who are not candidates for conventional revascularization procedures. In
      addition, EPCs can be used to promote vascular graft patency. This review focuses
      on the characterization of EPCs, positive and negative regulators of EPCs, the
      role of EPCs in vascular disease, and the potential for EPC therapy to ameliorate
      the sequelae of severe peripheral vascular disease.

PMID- 18053427
TI  - Early detection and biomarkers in pancreatic cancer.
AB  - Major advances in cancer control will be greatly aided by early detection for
      diagnosing and treating cancer in its preinvasive state before metastasis.
      Unfortunately, for pancreatic ductal adenocarcinoma (PDAC), which is the fourth
      leading cause of cancer-related death in the United States, effective early
      detection and screening are currently not available and tumors are typically
      diagnosed at a late stage, frequently after metastasis. Partly because of low
      sensitivity/specificity, existing biomarkers such as CA19-9 are not adequate as
      early detection markers of pancreatic cancer. Thus, a great need exists for new
      biomarkers for pancreatic cancer. This article focuses on recent developments in
      the identification of new serum protein biomarkers that are useful in the early
      detection of PDAC.

PMID- 18053426
TI  - Pancreatic adenocarcinoma. Clinical Practice Guidelines in Oncology.

PMID- 18053428
TI  - Targets, trials, and travails in pancreas cancer.
AB  - Pancreas cancer is a highly aggressive and rapidly fatal disease. The current
      standard of care for advanced disease improves survival modestly at best and
      provides palliation for a minority of patients. The need for new therapies is
      undisputed. This article describes new therapeutic strategies currently under
      investigation and discusses possible reasons that others have failed. New
      potential targets in the treatment of this formidable disease are suggested based
      on recent findings.

PMID- 18053429
TI  - Cancer-related fatigue. Clinical Practice Guidelines in Oncology.

PMID- 18053430
TI  - Update on psychotropic medications for cancer-related fatigue.
AB  - Fatigue is a common and highly distressing symptom of cancer associated with
      reduced quality of life and considerable psychological and functional morbidity.
      The reported prevalence of cancer-related fatigue ranges from 4% to 91%,
      depending on the specific cancer population studied and the methods of
      assessment. Cancer-related fatigue has typically been underreported,
      underdiagnosed, and undertreated. Fatigue and depression may coexist in cancer
      patients, and considerable overlap of symptoms occurs. This is partly the reason
      for the interest in examining the role of psychotropic medications in treating
      fatigue. Clarifying the relationship between depression and fatigue is necessary
      to effectively evaluate and treat cancer-related fatigue. Even with International
      Classification of Diseases criteria, differentiating cancer-related fatigue is
      difficult. Psychotropic drugs that have been studied for cancer-related fatigue
      include psychostimulants, wakefulness-promoting agents, and antidepressants.
      Methylphenidate has been studied most and seems to be effective and well
      tolerated despite common side effects. Some preliminary data support using
      modafinil in cancer-related fatigue with less concern about tolerance or
      dependence. Antidepressant studies have shown mixed results. Paroxetine seems to
      show benefit for fatigue primarily when it is a symptom of clinical depression.
      Bupropion, a norepinephrine/dopamine reuptake inhibitor, may have psychostimulant
      like effects, and therefore may be more beneficial for treating fatigue. However,
      studies are currently limited. Randomized, placebo-controlled trials with
      specific agents are needed to further assess the efficacy and tolerability of
      psychotropic medications in the treatment of cancer-related fatigue.

PMID- 18053431
TI  - Implementing the Fatigue Guidelines at one NCCN member institution: process and
      outcomes.
AB  - Fatigue, despite being the most common and distressing symptom in cancer, is
      often unrelieved because of numerous patient, provider, and system barriers. The
      overall purpose of this 5-year prospective clinical trial is to translate the
      NCCN Cancer-Related Fatigue Clinical Practice Guidelines in Oncology and NCCN
      Adult Cancer Pain Clinical Practice Guidelines in Oncology into practice and
      develop a translational interventional model that can be replicated across
      settings. This article focuses on one NCCN member institution's experience
      related to the first phase of the NCCN Cancer-Related Fatigue Guidelines
      implementation, describing usual care compared with evidence-based guidelines.
      Phase 1 of this 3-phased clinical trial compared the usual care of fatigue with
      that administered according to the NCCN guidelines. Eligibility criteria included
      age 18 years or older; English-speaking; diagnosed with breast, lung, colon, or
      prostate cancer; and fatigue and/or pain ratings of 4 or more on a 0 to 10
      screening scale. Research nurses screened all available subjects in a cancer
      center medical oncology clinic to identify those meeting these criteria.
      Instruments included the Piper Fatigue Scale, a Fatigue Barriers Scale, a Fatigue
      Knowledge Scale, and a Fatigue Chart Audit Tool. Descriptive and inferential
      statistics were used in data analysis. At baseline, 45 patients had fatigue only
      (> or = 4) and 24 had both fatigue and pain (> or = 4). This combined sample (N =
      69) was predominantly Caucasian (65%), female (63%), an average of 60 years old,
      diagnosed with stage 3 or 4 breast cancer, and undergoing treatment (82%). The
      most common barriers noted were patients' belief that physicians would introduce
      the subject of fatigue if it was important (patient barrier); lack of fatigue
      documentation (professional barrier); and lack of supportive care referrals
      (system barrier). Findings showed several patient, professional, and system
      barriers that distinguish usual care from that recommended by the NCCN Cancer
      Related Fatigue Guidelines. Phase 2, the intervention model, is designed to
      decrease these barriers and improve patient outcomes over time, and is in
      progress.

PMID- 18053436
TI  - Stress ulcer prophylaxis: overuse is understated.

PMID- 18053437
TI  - Onychomycosis is more than a cosmetic concern.

PMID- 18053438
TI  - Azithromycin for PID beats doxycycline on all counts.

PMID- 18053439
TI  - Is it DVT? Wells score and D-dimer may avert costly workup.

PMID- 18053440
TI  - Annual zoledronic acid infusion lowers risk of fracture, death.

PMID- 18053441
TI  - Hooked from the first cigarette.

PMID- 18053442
TI  - Itchy perianal erythema.

PMID- 18053443
TI  - Empathy goes a long way in weight loss discussions.
AB  - PURPOSE: This study explores how weight-related topics are discussed between
      physicians and their overweight and obese female patients. METHODS: We surveyed
      and audio-recorded preventive health and chronic care visits with 25 overweight
      and obese female patients. We coded both for quantity (content and time) of
      weight-related discussions and quality (adherence to Motivational Interviewing
      [MI] techniques). We then tested correlations of these measures with patients'
      reported attempts to lose weight, change diet, and change exercise patterns 1
      month after the visit. RESULTS: Weight was routinely addressed (19 of 25
      encounters). Patients usually initiated the topic (67% of time). Physicians' use
      of MI techniques resulted in patients attempting to lose weight and changing
      their exercise patterns. CONCLUSION: Physicians may benefit from MI training to
      help patients lose weight.

PMID- 18053444
TI  - An unusual case of chest pain.

PMID- 18053445
TI  - Clinical inquiries. What is the risk of bowel strangulation in an adult with an
      untreated inguinal hernia?

PMID- 18053446
TI  - Clinical inquiries. Are steroid injections effective for tenosynovitis of the
      hand?

PMID- 18053447
TI  - Clinical inquiries. How should you document a patient's refusal to undergo a
      necessary intervention?

PMID- 18053448
TI  - Clinical inquiries. What is the best treatment for chronic constipation in the
      elderly?

PMID- 18053449
TI  - Prominent J wave in accidental hypothermia.

PMID- 18053450
TI  - Monoclonal gammopathy of undetermined significance: genetic vs environmental
      etiologies.

PMID- 18053451
TI  - Advance directives: know what you want, get what you need.

PMID- 18053452
TI  - Methicillin-resistant Staphylococcus aureus: the latest health scare.

PMID- 18053453
TI  - Prevalence of monoclonal gammopathy of undetermined significance among men in
      Ghana.
AB  - OBJECTIVE: To determine the prevalence of monoclonal gammopathy of undetermined
      significance (MGUS), a precursor of multiple myeloma (MM), in Ghanaian men vs
      white men and to test for evidence to support an underlying race-related
      predisposition of the 2-fold higher prevalence of MGUS in African Americans vs
      whites. PARTICIPANTS AND METHODS: Between September 1, 2004, and September 30,
      2006, 917 men (50-74 years) underwent in-person interviews and physical
      examinations. Serum samples from all participants were analyzed by
      electrophoresis performed on agarose gel; any serum sample with a discrete or
      localized band was subjected to immunofixation. Age-adjusted and standardized (to
      the 2000 world population) prevalence estimates of MGUS and 95% confidence
      intervals (CIs) were computed in the Ghanaian men and compared with MGUS
      prevalence in 7996 white men from Minnesota. Associations between selected
      characteristics and MGUS prevalence were assessed by the Fisher exact test and
      logistic regression models. RESULTS: Of the 917 study participants, 54 were found
      to have MGUS, yielding an age-adjusted prevalence of 5.84 (95% CI, 4.27-7.40) per
      100 persons. No significant variation was found by age group, ethnicity,
      education status, or prior infectious diseases. The concentration of monoclonal
      immunoglobulin was undetectable in 41 (76%) of the 54 MGUS cases, less than 1
      g/dL in 10 patients (19%), and 1 g/dL or more in only 3 patients (6%). Compared
      with white men, the age-adjusted prevalence of MGUS was 1.97-fold (95% CI, 1.94
      2.00) higher in Ghanaian men. CONCLUSION: The prevalence of MGUS in Ghanaian men
      was twice that in white men, supporting the hypothesis that race-related genetic
      susceptibility could explain the higher rates of MGUS in black populations. An
      improved understanding of MGUS and MM pathophysiology would facilitate the
      development of strategies to prevent progression of MGUS to MM.

PMID- 18053454
TI  - Prevalence of monoclonal gammopathy of undetermined significance: study of 52,802
      persons in Nagasaki City, Japan.
AB  - OBJECTIVE: To assess the prevalence of monoclonal gammopathy of undetermined
      significance (MGUS) in a large Japanese population. PARTICIPANTS AND METHODS:
      From October 1, 1988, to March 31, 2004, a total of 52,802 (of 71,675) Japanese
      survivors of the atomic bomb explosion in Nagasaki City, Japan, were screened for
      M protein. The youngest participant was 42.3 years as of October 1, 1988. A 2
      step screening was performed with a serum protein electrophoresis followed by
      immunoelectrophoresis and a quantitative determination of serum concentration of
      immunoglobulins. Twenty-one patients who were diagnosed for the first time at the
      time of screening as having multiple myeloma and Waldenstrom macroglobulinemia
      were excluded from analyses. Age- and sex-specific prevalence rates of MGUS were
      calculated. RESULTS: Monoclonal gammopathy of undetermined significance was
      identified in 1088 of the 52,781 study participants. The overall prevalence of
      MGUS was 2.1% (95% confidence interval [CI], 1.9%-2.2%) in the total population
      screened and 2.4% (95% CI, 2.0%-2.6%) in those 50 years or older. The prevalence
      was significantly higher in men than in women (2.8% vs 1.6%; age-adjusted odds
      ratio, 2.0; 95% CI, 1.8-2.3; P less than .001). In both sexes, the prevalence
      rose with increasing age from 1.0% in participants aged 42 to 49 years, 1.9% in
      those 50 to 59 years, 2.6% in those 60 to 69 years, and 3.0% in those 70 to 79
      years, to 4.4% in those 80 years and older. The heavy chain isotypes of
      immunoglobulin were IgG in 73.6% of patients, IgA in 17.7%, IgM in 7.5%, and
      oligoclonal gammopathies in 1.1%. CONCLUSION: The prevalence of MGUS is lower in
      this Japanese population than that reported in Western countries among people
      older than 60 years, especially among women.

PMID- 18053455
TI  - Patients who complete advance directives and what they prefer.
AB  - OBJECTIVE: To determine health care preferences expressed by patients in advance
      directives (ADs) and to identify characteristics of patients who completed them.
      PATIENTS AND METHODS: A computer-generated random sample of 500 patients was
      selected from the 25,865 (margin of error, +/- 4.34%) unique patients who
      submitted ADs to Mayo Clinic Rochester between January 1, 2004, and July 1, 2005.
      After excluding 24 (4.8%) patients who had submitted documents related to
      financial and property matters instead of ADs, we analyzed the contents of the
      476 ADs and the demographic features of the patients to whom the documents
      belonged. RESULTS: The median (range) age of the patients at the time they signed
      their respective ADs was 67 (19-97) years. Of the 476 study patients, 409 (91.3%)
      were high school graduates; 339 (71.2%) had submitted a combined AD, which has
      features of a living will and a health care power of attorney; 434 (91.2%) had
      designated a health care agent; and most had granted the agent powers to consent
      for procedures (340 [78.3%]), to access information (327 [75.3%]), and to
      withhold and withdraw life-sustaining treatments (337 [77.6%]). Most patients
      expressed a desire for pain control (308 [64.7%]). For the clinical situations of
      dying or permanent unconsciousness, most patients explicitly expressed a
      preference to avoid "general life support" (371 [77.9%]) but did not explicitly
      address common life-sustaining treatments, including cardiopulmonary
      resuscitation, mechanical ventilation, hemodialysis, blood transfusion, and
      artificial nutrition and hydration (if they did, nearly all expressed a
      preference to avoid the treatments). CONCLUSION: In ADs submitted to our
      institution, most patients designated a health care agent and granted the agent
      broad decision-making powers. Although most expressed a desire to avoid "general
      life support" if dying or permanently unconscious, few expressed preferences
      regarding specific life-sustaining treatments. Patients, clinicians, and others
      who use ADs, and investigators contemplating research involving ADs, might find
      these results informative.

PMID- 18053456
TI  - Advance directives among health care professionals at a community-based cancer
      center.
AB  - OBJECTIVE: To determine the proportion of health care professionals at our
      community-based cancer center who had completed advance directives (ADs) and to
      identify barriers to their doing so. PARTICIPANTS AND METHODS: On October 11,
      2005, we sent a Web-based survey via e-mail to 170 health care professionals who
      have face-to-face contacts with patients at our institution. These health care
      professionals included medical (physicians, n=15), associate (physician
      assistants and nurse practitioners, n=7), and support (nurses, radiation
      therapists, medical or nurse assistants, social workers, nutritionists,
      geneticist, chaplain, family counselor, and patient liaisons; n=148) staff
      members. The survey ended on October 31, 2005. For the purpose of this survey,
      having a written AD was defined as having both a living will and a power of
      attorney for health care. Key outcome measures of our study were existence of
      ADs, placement of ADs in the medical record, communication of ADs with loved ones
      and primary care physician, and factors that influenced the decision to have an
      AD. Statistical tests included the chi2 and Fisher exact tests. RESULTS: Of the
      170 health care professionals to whom the survey was sent, 134 (79%) responded.
      Although 83% reported that they had discussed their wishes regarding future life
      sustaining medical care with those closest to them, only 35% had a written AD
      (58% of medical staff, 50% of associate staff, and 32% of support staff). Among
      those with ADs, 66% had informed their primary care physician, and 71% were
      certain that their ADs were in their medical records. Older age (P less than
      .001), role as medical or associate staff (P=.05), and more years of work
      experience with patients with cancer (P=.05) were associated with having an AD,
      whereas sex, marital or partnership status, and number of children were not.
      Perceived lack of time was the most common barrier cited (45%). Among those
      without an AD, 75% reported having end-of-life discussions with family members or
      loved ones. CONCLUSION: Despite work experience with patients who have a high
      mortality rate, health care professionals at our cancer center do not adequately
      communicate (via a written AD) end-of-life planning decisions to their own
      primary care physicians.

PMID- 18053457
TI  - Systematic review and meta-analysis of real-world adherence to drug therapy for
      osteoporosis.
AB  - OBJECTIVE: To quantify the adherence of patients to drug therapy for osteoporosis
      in real-world settings via a systematic review and meta-analysis of observational
      studies. METHODS: The PubMed and Cochrane databases were searched for English
      language observational studies published from January 1, 1990, to February 15,
      2006, that assessed patient adherence to drug therapy for osteoporosis using the
      following medical subject headings and keywords: drug therapy, medication
      adherence, medication persistence, medication possession ratio, patient
      compliance, and osteoporosis. Studies were stratified into 3 groups: persistence
      (how long a patient continues therapy), compliance (how correctly, in terms of
      dose and frequency, a patient takes the medication), and adherence (a combination
      of persistence and compliance). A random-effects model was used to pool results
      from the selected studies. RESULTS: Twenty-four studies were included in the meta
      analysis. The pooled database-derived persistence rate was 52% (95% confidence
      interval [CI], 44%-59%) for treatment lasting 1 to 6 months, 50% (95% CI, 37%
      63%) for treatment lasting 7 to 12 months, 42% (95% CI, 20%-68%) for treatment
      lasting 13 to 24 months, returning to 52% (95% CI, 45%-58%) for treatment lasting
      more than 24 months. Pooled adherence rates decreased from 53% (95% CI, 52%-54%)
      for treatment lasting 1 to 6 months to 43% for treatment lasting 7 to 12 months
      (95% CI, 38%-49%) or 13 to 24 months (43%; 95% CI, 32%-54%). The pooled refill
      compliance estimate was 68% (95% CI, 63%-72%) for treatment lasting 7 to 12
      months and 68% (95% CI, 67%-69%) for treatment lasting 13 to 24 months. The
      pooled self-reported compliance rate was 62% (95% CI, 48%-75%) for treatment
      lasting 1 to 6 months and 66% (95% CI, 45%-81%) for treatment lasting 7 to 12
      months. CONCLUSION: One-third to half of patients do not take their medication as
      directed. Nonadherence occurs shortly after treatment initiation. Terms and
      definitions need to be standardized to permit comparability of technologies
      designed to improve patient adherence. Prospective trials are needed to assess
      the relationship between adherence and patient outcomes.

PMID- 18053458
TI  - Safety of percutaneous dilatational tracheostomy with direct bronchoscopic
      guidance for solid organ allograft recipients.
AB  - OBJECTIVE: To determine the safety of percutaneous dilatational tracheostomy
      (PDT) for solid organ allograft recipients, who have increased risks of bleeding
      and infection. PARTICIPANTS AND METHODS: We reviewed the records of patients who
      underwent solid organ transplant between January 1, 2001, and September 30, 2005,
      followed by PDT (using the Ciaglia technique) with direct bronchoscopic guidance.
      We recorded comorbid conditions, number of days from intubation and transplant,
      positive end-expiratory pressures, ratios of PaO2 to fraction of inspired oxygen,
      coagulation study findings, complications, and procedure-related mortality rates.
      RESULTS: Of the 51 patients in our study, 17 had undergone lung transplant; 32,
      liver transplant; and 2, kidney transplant. The median age was 55 years (range,
      27-73), and 53% of patients were men. The median time from intubation to PDT was
      10 days and from transplant to PDT, 22 days. The median ratio of PaO2 to fraction
      of inspired oxygen was 293, and the median positive end-expiratory pressure was 5
      cm H2O. Twenty-one patients were receiving dialysis, and 11 were recovering from
      sepsis (of these, 8 were receiving vasopressors). Ten had coagulopathies (none of
      which were associated with bleeding complications). Complications were infrequent
      (7 periprocedural, 4 postprocedural) and included bleeding, bradycardia,
      hypotension, tracheal ring fracture, and cannula malfunction. Of the bleeding
      complications, only 2 were clinically remarkable and required removal of the
      tracheostomy or surgical revision. No infectious complications or procedure
      related deaths were noted. CONCLUSION: Percutaneous dilatational tracheostomy was
      tolerated well in recipients of solid organ allografts and had a relatively low
      risk of major complications and a low procedure-related mortality rate. This
      method should be considered an acceptable alternative to surgical tracheostomy.

PMID- 18053459
TI  - Remitting seronegative symmetrical synovitis with pitting edema syndrome in a
      rural tertiary care practice: a retrospective analysis.
AB  - OBJECTIVE: To review the clinical and laboratory features of remitting
      seronegative symmetrical synovitis with pitting edema (RS3PE) in a rural tertiary
      care rheumatology practice, describe treatments and outcomes, and compare our
      results to previous reports in the literature. PATIENTS AND METHODS: We performed
      a retrospective chart review of all patients diagnosed as having RS3PE who were
      seen in the Department of Rheumatology at Geisinger Medical Center, Danville, PA,
      from January 1, 1992, to December 31, 2005. RESULTS: We identified 12 men and 2
      women, all of whom were white. Mean +/- SD age was 74.0 +/- 6.6 years; mean +/-
      SD erythrocyte sedimentation rate was 35.9 +/- 21.1 mm/h at presentation. Onset
      of illness was sudden in 9 patients and insidious in 5. All patients were
      initially treated with prednisone (15-20 mg/d). Although the response in all was
      excellent, 9 patients received disease-modifying antirheumatic drugs, either
      because of ongoing disease activity or in an effort to decrease the use of
      corticosteroids. Hydroxychloroquine was used alone in 7 patients. At the mean +/-
      SD time of last follow-up (31.4 +/- 23.1 months), 5 patients continued to receive
      therapy. Complications of treatment included worsening of preexisting
      hypertension in 3 patients, gastritis in 2, and exacerbation of preexisting
      diabetes mellitus in 1. Carpal tunnel syndrome occurred in 6 patients. Duration
      of therapy ranged from 5 to 120 months (mean, 29 months). Three patients
      developed malignancies, ie, non-Hodgkin lymphoma, transitional cell carcinoma of
      the bladder, and prostate carcinoma. CONCLUSION: Our population of patients with
      RS3PE is similar to those documented in previous reports: elderly, predominantly
      male, and responsive to corticosteroids. However, our series is clinically
      differentiated by a greater use of adjunctive disease-modifying antirheumatic
      drugs (primarily hydroxychloroquine). Confirming previous reports, we also
      observed a possible association between RS3PE and malignancy.

PMID- 18053460
TI  - Septal myectomy after previous septal artery ablation in hypertrophic
      cardiomyopathy.
AB  - OBJECTIVE: To review our institution's experience with patients who failed to
      benefit from septal artery ablation, which necessitated subsequent septal
      myectomy, and to examine reasons for ablation failure and outcome of myectomy
      after ablation. PARTICIPANTS AND METHODS: Of 550 patients who underwent septal
      myectomy at Mayo Clinic Rochester between January 1, 1999, and December 31, 2006,
      16 (3%) had had a total of 22 previous septal artery ablations. This subset of 16
      patients was analyzed and compared with a reference group of 120 patients whose
      septal artery ablations were performed at our institution during this period.
      Angiograms obtained during septal ablation were available for 13 (81%) of 16
      patients in this series and were reviewed by 2 interventional cardiologists
      (R.A.N. and S.R.O.). These cardiologists also reviewed preoperative and
      postoperative echocardiography data, hospital course, and follow-up data to
      compile a list of characteristics that could have contributed to failed ablation.
      RESULTS: The median age of the patients at operation was 65 years (interquartile
      range [IQR], 52-72 years), and interval between ablation and myectomy was 409
      days (IQR, 162-568 days). Angiograms revealed 2 failed procedures secondary to
      technical error. One patient had a relatively large first septal perforator with
      a large resting gradient. In 10 patients no septal perforators supplying the
      proximal septum were identified. Postoperatively, mitral regurgitation decreased
      from 3.00 to 1.00 (P less than .001), and left ventricular outflow tract gradient
      decreased from 75 mm Hg to 0 mm Hg (IQR, 0-29 mm Hg; P less than .001). Two
      patients died after surgery: 1 patient developed multiple-organ system failure on
      postoperative day 7, and 1 patient developed arrhythmia on postoperative day 21.
      Patients with previous septal artery ablation were older (P=.04), were more
      likely to have preoperative permanent pacemakers or implantable cardioverter
      defibrillators (P=.05), were more likely to require postoperative pacemaker
      placement (P less than .001), and had higher operative mortality (P less than
      .001) than control patients. Fourteen patients survived the early recovery phase;
      9 were followed up at a median of 1.88 years (IQR, 306 days to 3.3 years). All
      patients' symptoms improved. Median gradient of the left ventricular outflow
      tract was 13 mm Hg (IQR, 0-15 mm Hg) at follow-up with mild to moderate (1.6)
      mitral regurgitation. CONCLUSION: Septal myectomy performed after failed ablation
      improves gradient and provides excellent relief of symptoms but is associated
      with a higher incidence of morbidity and mortality.

PMID- 18053461
TI  - Use of random skin biopsy for diagnosis of intravascular large B-cell lymphoma.
AB  - Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma with an
      aggressive clinical course characterized by proliferation of large lymphoma cells
      within the lumina of the small vessels. Because of its varied clinical symptoms
      and the absence of lymphadenopathy, diagnosis of IVL is extremely difficult and
      requires histological confirmation. We report here 6 consecutive patients with
      IVL, admitted to Kameda General Hospital, Kamogawa-shi, Japan, from June 7, 2006,
      to February 28, 2007, whose IVL was diagnosed by random skin biopsy of healthy
      appearing skin. Three patients presented with progressive neurological
      deterioration and 2 others with hypoxemia with interstitial infiltration on chest
      radiography. One patient presented with confusion and severe hypoxia without
      apparent interstitial infiltration. Two patients showed localized skin
      involvement. Irrespective of the presence of skin lesions, almost all skin biopsy
      specimens showed obliteration of small vessels of subcutaneous fat tissues by
      lymphoma cells, allowing a prompt diagnosis of IVL. Early institution of
      rituximab-based chemotherapy induced favorable responses in all patients treated.
      Because diagnosis based on tissue other than skin is usually difficult in
      patients with suspected IVL, random skin biopsy should be considered even in
      patients with no evident skin lesions.

PMID- 18053462
TI  - Understanding and engaging the hostile patient.

PMID- 18053463
TI  - Seizures among public figures: lessons learned from the epilepsy of Pope Pius IX.
AB  - Epilepsy is one of the most stigmatizing of neurological conditions.
      Understanding how epilepsy affects the lives of important historical figures
      illuminates the psychosocial burden of disease for modern-day patients. Pius IX,
      one of the most consequential Popes in Catholic history, was reported to have
      epilepsy. Thus, this study aimed to assess how epilepsy influenced Pope Pius IX's
      life and his papacy. Librarians from Mayo Clinic, Library of Congress, and
      Vatican Library were consulted to identify all sources pertaining to Pius IX's
      health history. Twenty-one sources were consulted, and we conclude that Pius IX
      had partial epilepsy, likely a temporal lobe focus with secondarily generalized
      seizures. A near-drowning event in his youth coupled with a preexisting central
      nervous system lesion (as evidenced by photos showing facial asymmetry) likely
      contributed to his epilepsy. Epilepsy played an important role in Pius IX's life
      because it led him to the Papacy. At least one doctrine (the immaculate
      conception of the Virgin Mary) was influenced by his seizures, but there is no
      direct evidence that epilepsy played any role in the creation of other Catholic
      dogma ratified during his reign. Analysis of bias in references showed that
      favorable views of the Pope tended to minimize any discussions of his epilepsy,
      whereas negative references discussed his epilepsy at length. Pius IX's life
      holds lessons for modern-day epilepsy advocacy.

PMID- 18053464
TI  - Eosinophilic esophagitis: is it all allergies?
AB  - Eosinophilic esophagitis (EE) is an increasingly recognized disorder in the adult
      population, most often manifested by symptoms of dysphagia and food impaction.
      Mechanisms involving eotaxin-3, interleukin 5, and signal transducer and
      activator of transcription 6 have been studied and may represent future
      therapeutic targets. Patients commonly have a personal and family history of
      atopy, and both food allergies and aeroallergens have also been investigated as
      triggers of EE. Traditional allergy-testing methods, including skin prick testing
      and specific IgE testing, have been used to identify food and environmental
      allergies. However, new studies suggest that patch testing could add to
      diagnostic accuracy in EE because the disorder might not be a classic type I
      allergic response. Although studies of treatment of adults with EE have thus far
      focused on swallowed fluticasone proprionate, many trials in children have
      assessed the efficacy of food elimination and elemental diets. These diets, which
      have been extremely successful in reducing symptoms, have also been shown to
      induce histological improvement and remission. No similar studies have been
      conducted in adults; the tolerability of such an intervention may prove more
      difficult in this population. This article reviews the underlying pathophysiology
      of EE and describes evolving options for more accurately identifying food and
      environmental allergies. We also discuss the pediatric trials using food
      elimination and avoidance diets and suggest that this type of intervention may be
      an important area of future research in the adult population.

PMID- 18053465
TI  - Emergency management and commonly encountered outpatient scenarios in patients
      with hyperkalemia.
AB  - Hyperkalemia is a common electrolyte disorder with potentially lethal
      consequences. Severe hyperkalemia can lead to life-threatening cardiac
      dysrhythmias, making a clear understanding of emergency management crucial.
      Recognition of patients at risk for cardiac arrhythmias should be followed by
      effective strategies for reduction in serum potassium levels. In the outpatient
      setting, diagnosis of hyperkalemia can be complicated by factitious elevations in
      serum potassium levels. True elevations in serum potassium levels are commonly
      due to medications used for cardiovascular disease in the setting of impaired
      glomerular filtration rate. The prevalence of chronic kidney disease is steadily
      increasing, likely leading to increases in risk of hyperkalemia. A systematic
      approach will aid in timely diagnosis and management of hyperkalemia.

PMID- 18053466
TI  - 66-year-old man with inarticulate speech.

PMID- 18053467
TI  - Prevention, diagnosis, and treatment of cervical cancer.
AB  - This article reviews the current data on human papillomavirus as the cause of
      most cervical cancer cases, data on the recently approved human papillomavirus
      vaccines, and updated information concerning the Bethesda System for
      interpretation of Papanicolaou test results. Current recommendations for surgical
      treatment, concurrent chemotherapy, and radiation therapy and recent advances in
      systemic therapy for advanced or metastatic cervical cancer are reviewed.

PMID- 18053468
TI  - Ethics consultations and patients with neurological diseases.

PMID- 18053469
TI  - Clinician attitudes toward biostatistics.

PMID- 18053470
TI  - [Importance of advanced age in infections: myth and reality].

PMID- 18053471
TI  - [Bacteremia in very elderly patients: risk factors, clinical characteristics and
      mortality].
AB  - INTRODUCTION: There is little information on bacteremia in very elderly patients.
      This study describes the characteristics of bacteremia in this population.
      METHODS: This is a prospective study investigating bacteremia episodes in
      patients over 80 years old in comparison with episodes in patients aged 18-64 and
      65-79 years. RESULTS: A total of 146 bacteremia episodes were analyzed in
      patients over 80 years old. Comorbidity was documented in 66.4% and
      immunodeficiency in 6.8% of patients. Among the total, 82.2% had no underlying
      disease or a disease considered non-fatal. Eighty episodes were community
      acquired. The main infectious foci included primary (25.3%) and urinary tract
      (20.5%) infection, and the most frequent isolates were Escherichia coli (28.2%),
      coagulase-negative Staphylococcus (14.7%) and S. aureus (13.6%). Sepsis or septic
      shock occurred in 55.5% of the cases, and 31 patients died due to a bacteremia
      related cause. Immunodeficiency was less frequent in patients over 80 years old,
      but they had a higher proportion of community-acquired infections and gram
      negative infections. Bacteremia-related mortality was highest in the oldest group
      of patients and was associated with a fatal or ultimately fatal underlying
      disease, S. aureus infection, and inappropriate empirical antibiotic treatment. A
      lower Pitt severity score was related to lower mortality risk. CONCLUSIONS: Very
      elderly bacteremic patients showed a lower frequency of immunodeficiency, a
      higher percentage of community-acquired and gram-negative infections. Bacteremia
      related mortality was greater in the most elderly group and was associated with
      fatal or ultimately fatal underlying disease, S. aureus infection and initiation
      of inappropriate empirical antibiotic treatment.

PMID- 18053472
TI  - [Gender analysis among articles published in Enfermedades Infecciosas y
      Microbiologia Clinica (2001-2005)].
AB  - BACKGROUND: There is growing concern for promoting equality between sexes and
      full integration of women in research activities. The purpose of this study is to
      identify the bibliometric characteristics of articles published during the 2001
      2005 period in Enfermedades Infecciosas y Microbiologia Clinica (EIMC) from the
      perspective of gender. METHOD: EIMC records for 2001-2005 were obtained from the
      Science Citation Index database and differences according to sex were calculated
      for the following indicators: year of publication, type of document, number and
      order of author signatures, number of collaborators, and the signature/article
      index at the institutional and geographical level. RESULTS: A total of 2,163
      authors were identified, 1,220 (56.4%) men and 943 (43.6%) women. The greatest of
      contribution from women was in original articles (42.32% of signatures).
      Excluding the Centro Nacional de Microbiologia (Spanish National Center for
      Microbiology), the participation of women was lower than men in the most
      productive institutions. There were significant differences regarding the number
      of papers published and the number of collaborators; with greater productivity
      for men and a higher rate of collaboration for women. DISCUSSION: Studies on
      scientific activity according to gender provide essential information to
      establish the basis for a policy of equality in this regard. A yearly increase of
      almost 1% was seen in the number of female authors contributing articles to the
      EIMC, which, if the trend continues, will result in parity in coming years.
      Nevertheless, the presence of women in positions of high productivity remains
      low. The causes of this difference should be identified and corrected.

PMID- 18053473
TI  - [Role of HLA-DR and HLA-DQ alleles in multibacillary leprosy and paucibacillary
      leprosy in the province of Chaco (Argentina)].
AB  - OBJECTIVES: Segregation analyses in several populations have suggested a
      relationship between specific human leukocyte antigen (HLA) class II alleles and
      the development of different types of leprosy. The aim of this study was to
      determine the frequency of HLA class II DR and DQ alleles among leprosy patients
      in Chaco province, northeast Argentina, in an effort to determine whether these
      alleles might be involved in the development of the multibacillary (MB) and
      paucibacillary (PB) forms of leprosy. PATIENTS AND METHODS: Samples from 89
      leprosy patients (MB = 70, PB = 19) and 112 healthy control subjects were
      analyzed. The HLA-DRB1 and HLA-DQB1 alleles were determined by PCR amplification
      and reverse hybridization with sequence-specific oligonucleotide probes, and
      analyzed with the INNO-LiPA typing system and LiPA software. DQB1*0201/0202/0203
      in patients with MB leprosy and DRB1*04 in patients with PB leprosy were detected
      at significantly lower frequencies as compared with the normal controls. RESULTS:
      These data indicate that DQB1* 0201/0202/0203 may be a protective factor in MB
      leprosy and DRB1*04 in PB leprosy. DISCUSSION: We attribute the differences
      between our findings and those of other authors to the fact that the Caucasian
      inhabitants of Chaco include a considerable mixture of South American natives
      (Guaranies and Tobas).

PMID- 18053474
TI  - [Microbiological diagnosis of HIV infection].
AB  - Currently, there are around 150,000 HIV-infected patients in Spain. This number,
      together with the fact that this disease is now a chronic condition since the
      introduction of antiretroviral therapy, has generated an increasing demand on the
      clinical microbiology laboratories in our hospitals. This increase has occurred
      not only in the diagnosis and treatment of opportunistic diseases, but also in
      tests related to the diagnosis and therapeutic management of HIV infection. To
      meet this demand, the Sociedad de Enfermedades Infecciosas y Microbiologia
      Clinica (Spanish Society of Infectious Diseases and Clinical Microbiology) has
      updated its standard Procedure for the microbiological diagnosis of HIV
      infection. The main advances related to serological diagnosis, plasma viral load,
      and detection of resistance to antiretroviral drugs are reviewed in this version
      of the Procedure.

PMID- 18053475
TI  - [Infection in lung transplantation].
AB  - Lung transplantation is now considered an established therapeutic option for
      patients with severe respiratory failure. Nevertheless, complications are
      frequent and can lead to intermediate- or long-term graft dysfunction and
      decreased survival. According to the registry of the International Society for
      Heart and Lung Transplantation, survival rates in these patients at one, two, and
      five years are 74%, 65%, and 47%, respectively. The main obstacle to long-term
      success of lung transplantation, however, is chronic rejection, which is
      characterized histologically as bronchiolitis obliterans and occurs in up to two
      thirds of patients. One of the most important risk factors for the development of
      bronchiolitis obliterans, in addition to the number of previous acute rejection
      episodes and the incidence of persistent rejection, is cytomegalovirus infection
      and disease. Moreover, recent evidence has indicated a role for respiratory
      viruses as risk factors for the development of chronic rejection in lung
      transplant recipients. Infectious complications are a frequent cause of morbidity
      and mortality in these patients and are the cause of death in nearly half of
      them. Bacterial infection is the most frequent infectious complication in lung
      transplant patients. Among the total of infections, 35%-66% are bacterial and 50%
      85% of patients present at least one episode. CMV is the second most frequent
      cause of infectious complications following lung transplantation. Despite the use
      of various preventive strategies, the risk of developing CMV disease in lung
      transplant recipients is over 5% during the first year. This is the only type of
      solid organ transplant in which the etiology of fungal infection is
      characteristically Aspergillus spp., in contrast to others in which infection by
      Candida spp. is most common. The incidence of invasive aspergillosis is about 4%.

PMID- 18053476
TI  - [A 70-year-old man with ulcerated chest wall lesions].

PMID- 18053477
TI  - [Asymptomatic lesions on the feet of a Spanish traveler coming from Tanzania].

PMID- 18053478
TI  - [About a patient with nalidixic-acid-resistant Salmonella enterica serotype typhi
      infection. Therapeutic management].

PMID- 18053479
TI  - [Probable case of imported human anaplasmosis].

PMID- 18053480
TI  - [ELISA test for the detection of Entamoeba histolytica in stool specimens].

PMID- 18053482
TI  - [Polymyositis-dermatomyositis: incidence in Spain (1997-2004)].
AB  - BACKGROUND AND OBJECTIVE: Epidemiologic studies of polymyositis-dermatomyositis
      incidence in Spain are lacking. The aim of the study was to determine the
      incidence rates of dermatomyositis-polymyositis and their distribution in our
      country. MATERIAL AND METHOD: Observational and descriptive study. Data was
      obtained from hospital discharge code (CMBD) during the period 1997-2004. Sex,
      region and age were analysed. Raw and standardized incidence rates for each
      region studied were calculated as new cases/million population/year with 95%
      confidence interval (CI). Trend odds ratio (OR) was calculated by means of a
      logistic regression. RESULTS: Global incidence rate in polymyositis
      dermatomyositis was 8.9 new cases/million population/year (CI 95%, 8.6-9.2); 3.9
      (CI 95%, 3.7-4.1) for polymyositis and 4.9 (CI 95%, 4.7-5.2) for dermatomyositis.
      Rate differences between both diseases reached statistical significance (p <
      0.001). Annual incidence rate decreased significantly across the period studied
      in both diseases with a trend OR of 0.95 (CI 95%, 0.93-0.97; p < 0.001) in
      dermatomyositis and 0.96 (CI 95%, 0.93-0.97; p < 0.001) in polymyositis. Both
      diseases were significantly more frequent in females (p < 0.001). The incidence
      rates for each region varies between 2.2 and 10.6 cases/million population/year
      in polymyositis and between 2.9 and 8.6 cases/million population/year in
      dermatomyositis. CONCLUSIONS: Incidence of dermatomyositis-polymyositis in Spain
      is similar to other countries. Decreased incidence observed across the period and
      the higher incidence of dermatomyositis could be explained because of a better
      diagnosis of these entities.

PMID- 18053481
TI  - [Association between meningeal Burkitt lymphoma and Epstein-Barr virus in an HIV
      infected patient].

PMID- 18053483
TI  - [CT colonography vs. barium enema for the preoperative study of colorectal cancer
      in patients with incomplete colonoscopy].
AB  - BACKGROUND AND OBJECTIVE: The complete preoperative evaluation of the colon is
      necessary in colorectal cancer owing to the frequency of synchronous tumors. The
      objective of this paper was to evaluate the utility of the computed tomography
      colonography (CTC) as opposed to barium enema (BEDC) when the colonoscopy was
      incomplete or impossible to perform. PATIENTS AND METHOD: Group A: 50 patients
      with colorectal cancer with subsequent incomplete colonoscopy and BEDC. Group B:
      40 patients with colorectal cancer with subsequent incomplete colonoscopy and
      CTC. As gold standard to match the tests, we carried out the pathological study
      of the surgical piece and the colonoscopy 3 months after surgery. In addition, we
      studied the degree of satisfaction, indirect effect and cost by test. RESULTS:
      There were no synchronous tumors. For the detection of colonic polyps, we
      obtained for the CTC the following values: Sensitivity = 85.7%, Specificity =
      96.1%, PPV = 92.3%, NPV = 92.6%, CPP = 21,97 and CPN =0,15. And for BEDC, the
      values were: Sensitivity = 23.5%, Specificity = 92.8%, PPV = 80%, NPV = 71.7%,
      CPP = 3.26 and CPN = 0.82 (p < 0.001). The degree of satisfaction was greater
      with CTC than with BEDC (p < 0.05). There were no differences as far as indirect
      effect was concerned. The cost of CTC was 33.18 Euros and it was 42.42 Euros for
      BEDC. CONCLUSION: CTC is better than BEDC both to confirm the presence of polyps
      in colon and to rule out the absence of them in patients in whom a complete the
      study of the colon by colonoscopy has not been possible.

PMID- 18053484
TI  - [Decrease of serum cholinesterase in colorectal cancer].
AB  - BACKGROUND AND OBJECTIVE: Cholinesterase is an enzyme with an unknown physiologic
      function. Some situations are related to a decreased serum cholinesterase
      activity but those situations are not well defined and the responsible mechanisms
      are unknown. Malignancy is one of these situations. The aim of the study was to
      compare the cholinesterase activity between patients with and without colorectal
      cancer. PATIENTS AND METHOD: Case-control study of patients with colorectal
      cancer who underwent surgery in our hospital from March 05 to January 07.
      RESULTS: Patients from the cancer group had a significant decreased serum
      cholinesterase activity. CONCLUSIONS: Investigation of cholinesterase function in
      humans may result in new research lines in oncology treatment.

PMID- 18053485
TI  - [Virtual colonoscopy in the preoperative study of colorectal cancer: a
      fundamental tool].

PMID- 18053486
TI  - [Should beta-blockers remain first choice in the treatment of primary
      hypertension?].

PMID- 18053487
TI  - [Therapeutic equivalence: concept and evidence levels].

PMID- 18053488
TI  - [Treatment of type 2 diabetes: revision of current therapeutical options and
      priorities].
AB  - The paradigm of type 2 diabetes mellitus treatment is based in an adequate meal
      plan and the regular practice of physical exercise. The benefits of these
      measures are of evident as it is the perseverance in their compliance. In the
      daily practice, this reality favours the early implementation of a
      pharmacological therapy that, in the opinion of different experts, would be
      simultaneous to the introduction of life style changes. In the last years, new
      drugs have been developed. On the one hand, there are agents with beneficial
      effects not only on blood glucose control but also on the components of metabolic
      syndrome. Other drugs, according to different experts, have doubtful
      therapeutical contribution. The appearance of new drugs to treat obesity,
      associated with diabetes or not, extends other possibilities of choice to take
      into account. The great variety of options makes the decision of the adequate
      therapy more difficult. In the last decade, many therapeutic guidelines have been
      developed, with convergences and divergences that may mislead the inexpert
      practitioners. In this review we propose some practical advise in diet and
      exercise, and an evaluation of the different drugs and rules of intervention
      proposed in the different therapeutic guidelines. The ultimate goal is to
      facilitate and direct type 2 diabetes management.

PMID- 18053489
TI  - [Superinfection by Balantidium coli of a pulmonary hydatidic cyst].

PMID- 18053490
TI  - [Dacrystic epilepsy secondary to meningioma].

PMID- 18053491
TI  - [Assistential ethics committees: is necessary the presence of a person in charge
      of the religious assistance?].

PMID- 18053492
TI  - [Adrenal hemosiderosis].

PMID- 18053493
TI  - [More is achieved when working together. Florence-2008-EfCCNa].

PMID- 18053494
TI  - [Stressful environmental events in the Intensive Care Unit].
AB  - The high standard of specialization of the Intensive Care Units (ICU) creates a
      stressful setting that generates anxiety and stress for the patients. This has
      been related to delirium or acute confusional syndrome. OBJECTIVES: To describe
      the stressful environmental events as perceived by patients an, to establish the
      differences between patients who suffered from delirium in ICU and those who did
      not suffer from it. MATERIAL AND METHODS: Descriptive crosssectional study that
      includes a qualitative part. A total of 91 patients were interviewed, 33 patients
      diagnosed of delirium in the ICU and 58 patients without this diagnosis.
      Ballard's Environmental stressful events scale with 43 items was used to
      determine the most stressful events. In addition, an open interview was carried
      out in which the patients could narrate their experiences in the ICU. Descriptive
      statistic was used to show the characteristics of patients selected and to
      determine the frequency distributions for each item inthe questionnaire. RESULTS:
      The factors perceived as the most stressful were: thirst(62.6%), sleep
      deprivation (42.9%), tubes in mouth or nose (35.2)and not knowing what time it
      was (34.1). Patients who suffered from delirium perceive disorientation or
      hallucinations as stressants CONCLUSIONS: As in previous investigations, ICU
      patiens, who did not suffered from delirium, perceived phisycal needs as most
      streesfull events.

PMID- 18053495
TI  - [Work-related stress (demand-control-social support model) and health
      alterations: a review of the existing evidence].
AB  - OBJECTIVE: To summarize the results obtained from epidemiological studies on the
      association of occupational stress and the development of illness in nurses or
      female population. METHODS: A descriptive review has been performed on studies
      published between 1979 and 2005 in which the Demand-Control-Social Support (DCS)
      model was used. Key words were focused on the DCS model and Occupational Health.
      The search was carried out using Medline (Pubmed), CINHAL, PsycINFO, and CUIDEN.
      RESULTS: A total of 36 articles were found. In 18 (50%) the study populations
      were nurses or workers in health areas. There is little evidence of the
      relationship between work-related stress and its repercussion on health. This
      could be justified because of the limited number of these longitudinal studies
      and the differences in the analysis of the model dimensions. CONCLUSIONS: The
      review of the literature does not offer consistent results. Longitudinal studies
      with longer follow-up periods that would make it possible to study the maintained
      effect of the exposure on health are needed.

PMID- 18053496
TI  - [Reliability of post-transfusional hematocrit].
AB  - Since the blood transfusion diseases, basically AIDS, have arisen in our society,
      the decision to administer a transfusion to a patient not only requires an
      informed consent but also must be fully justified and documented. This implies
      that, except for emergencies, the hematocrit value must be measured previously.
      However, if the patient has just received a transfusion and due to the phenomenon
      of hemoconcentration, the reliability of this analysis during the first hours
      following the transfusion period is questionable. In fact, and according to the
      health care site in question, this time varies from a half hour to up to six
      hours. Not in vain, up to now, we only have one study that approaches this
      subject applying the scientific method, although it is limited to pediatrics. Our
      research team has established the purposes of <<knowing the variations of the
      post-transfusional hematocrit in relationship with time>>, beginning with the
      hypothesis <<the post-transfusional hematocrit value does not undergo relevant
      modifications as a consequence of the passing of time.>> Based on the
      quantitative approach, we designed an experimental study in which we considered
      the hematocrit value as the dependent variable and time as the independent
      variable. As a result, we obtain that the comparison between the immediate
      analysis and the subsequent ones does not offer statistically significant
      differences. We conclude that it is possible to make the analysis coinciding with
      the end of the transfusion, with total reliability.

PMID- 18053497
TI  - [Non-invasive ventilation in the Intensive Care Units. Part I: background and
      interphase].
AB  - INTRODUCTION: Non-invasive ventilation is a respiratory support method that has
      gained ground in the management of patients with acute respiratory failure.
      Currently, it has become a first line instrument in the treatment of respiratory
      failure of the critical patient. Scientific evidence supports its use in patients
      with acute lung edema, acute hypercapnic respiratory failure, immunosuppressed
      patients and patients with atelectasis. The objectives of this review are 1,
      introduce the reader to the non-invasive ventilation; 2, inform on the basics of
      its use in critical patients; and 3, the management of the interphase in acute
      situations. To do so, the bibliography available on it in databases (Medline and
      Cochrane) and published textbooks were used. CONCLUSIONS: The characteristics of
      the technique require careful dedication of the health care personnel, with
      adequate knowledge about the technology involved in addition to the collaboration
      of the patients to make it successful.

PMID- 18053498
TI  - [Permissive hypotension in resuscitation of trauma patients].

PMID- 18053499
TI  - [Repair of secondary aortoenteric fistulas. A systematic review].
AB  - We performed a systematic review of the literature on the diagnosis and treatment
      of secondary aortoenteric fistulas (AEF). A MEDLINE search was performed of
      articles published in English or Spanish between January 1991 and August 2006.
      Diagnostic methods, treatment modalities and the results of surgical treatment
      were analyzed. The most frequent first aortic surgery associated with AEF was
      repair of abdominal aortic aneurysm (54.31%). The most common form of
      presentation was gastrointestinal bleeding. Repair through in situ prosthetic
      replacement had the lowest early mortality rates (8-13.3%) compared with graft
      excision and extraanatomic revascularization (18.2-44%). AEF is a serious entity
      and diagnosis requires a high index of suspicion based on clinical findings and
      indirect data from imaging techniques (computed tomography). The most appropriate
      therapeutic option continues to be controversial.

PMID- 18053500
TI  - [Surgery and blood transfusion in Jehovah's witnesses: a medical-legal review].
AB  - Conflict between two ethical and legal conditions such as life and freedom is
      frequent in medical practice. Jurisdiction has handed down contradictory
      decisions and edicts when placing life (and therefore the lex artis of
      physicians) above Jehovah's witnesses' right to refuse blood transfusions.
      However, in principle, the right to life takes precedence over the patient's
      autonomy because, based on professional ethics, physicians have a duty to attempt
      a cure. Thus the patient's liberty is infringed, giving rise to interventions
      that may give rise to complaints and lawsuits. The present article provides an
      overview of each and every situation that could give rise to doubts, as well as
      an analysis of jurisdiction and the legal responsibilities involved in surgical
      decisions about Jehovah's witnesses.

PMID- 18053501
TI  - [Results of a medication reconciliation project in routine medical treatment
      after surgical discharge].
AB  - OBJECTIVE: To reduce the number of medication-related problems by ensuring
      reconciliation between ambulatory treatment and surgical prescription and to
      increase patients' understanding of drug therapy and treatment adherence.
      MATERIAL AND METHOD: Information on ambulatory medication was obtained through a
      personal interview and a review of the patient's personal and pharmacotherapeutic
      history. A dossier was created that included detailed information on each
      medication and a chronopictogram with all doses. On the day of discharge, a
      second interview with the patient was performed in which information was obtained
      orally and in writing about all treatment. The process was evaluated through a
      satisfaction questionnaire. Two weeks after discharge a telephone interview was
      carried out to detect post-discharge medication-related problems. RESULTS: During
      the study period (April-December 2006) 544 patients were included. There were 658
      pharmaceutical interventions: 87% educational, 8% safety, 5% efficiency. A total
      of 346 satisfaction questionnaires were properly completed (63% of those
      distributed). Responses to questionnaires were evaluated from 0 (completely
      dissatisfied) to 5 (highly satisfied). Interest in the information received was
      scored 4.75, understanding of the information 4.67, and satisfaction with the
      intervention 4.59. CONCLUSIONS: Including the pharmacist in the surgical team
      ensures reconciliation between ambulatory treatment and surgical prescription and
      reduces medication errors. Providing information to patients about their
      medication at discharge increases their understanding of drug treatment and
      adherence.

PMID- 18053502
TI  - [Biliary reconstruction in liver transplantation: is a biliary tutor necessary?].
AB  - OBJECTIVES: To assess the incidence and type of biliary complications in liver
      transplantation after biliary reconstruction with or without a biliary tutor.
      MATERIAL AND METHOD: A prospective, non-randomized study of 128 consecutive
      patients undergoing elective liver transplantation was performed.
      Retransplantations, emergency transplantations, hepaticojejunostomy and patients
      who died within 3 months of causes other than biliary complications were
      excluded. Group I (n = 64) underwent termino-terminal choledochocholedochostomy
      with a Kehr tube and group II (n = 64) underwent choledochocholedochostomy
      without Kehr tube. Complications, therapeutic procedures, reoperations and
      survival free of biliary complications were analyzed. RESULTS: The overall rate
      of biliary complications was 15% (17% in group I and 14% in group II). Types of
      complication (overall and in groups I and II, respectively) consisted of fistulas
      4% (6% vs. 3%), stenosis 8% (4% vs. 12%), and Kehr dysfunction 3%. The mean
      number of therapeutic procedures, including endoscopic retrograde
      cholangiopancreatography, percutaneous transhepatic cholangiography, trans-Kehr
      cholangiography and drainage of collections, was 2.1 vs. 2 per complicated
      patient. The overall reoperation rate was 5% (2% vs. 9%) (p < 0.05). One-year
      survival free of biliary complications was 85% vs. 82% (Log Rank = 0.5).
      CONCLUSIONS: No statistically significant differences were found in complications
      after choledocho-choledocho anastomosis with or without a biliary tutor. However,
      the patient group that did not receive a biliary tutor required more complex
      procedures for treatment of complications, as well as a greater number of
      reoperations.

PMID- 18053503
TI  - [Gastric cancer in patients older than 75 years. Surgical treatment and long-term
      survival].
AB  - INTRODUCTION: The characteristics and results of radical gastrectomy for gastric
      cancer in elderly patients are controversial. Aim. To analyze the
      clinicopathologic characteristics and the results of gastrectomy for cancer in a
      group of patients > or = 75 year old. MATERIAL AND METHOD: A series of 442
      patients who underwent surgery for gastric cancer was divided into group A (< 75
      years old) and group B (> or = 75 years old). The clinicopathologic
      characteristics, results of gastrectomy, and long-term survival were compared.
      RESULTS: The mean age was 62 +/- 13 years. There were 361 patients in group A and
      81 patients in group B. Tumoral location in the upper third of the stomach was
      more frequent in group A than in group B (36.8% vs 24.7%), while localization in
      the lower third of the stomach was more frequent in group B than in group A
      (50.6% vs 29.4%) (p < 0.05). Total gastrectomy was performed in 66% of patients
      in group A and in 38% of those in group B (p < 0.05); 27.3 +/- 3.5 nodes were
      resected in group A and 19.5 +/- 0.7 in group B (p < 0.05). No differences were
      found in the frequency of complications (16%) or in overall operative mortality
      between the two groups. However, mortality in total gastrectomy was higher in
      group B (6.4%) than in group A (3.8%) (p < 0.05). No differences in 5-year
      survival were found between the two groups (44.3% in group A and 44.4% in group
      B). CONCLUSIONS: In patients aged more than 75 years old, tumors were more
      frequently located in the distal third of the stomach. Age above 75 years does
      not seem to be a prognostic factor and long-term results depend more on disease
      stage.

PMID- 18053504
TI  - [Peritoneal carcinomatosis. Ten years of applying the new combined triple
      therapy. Personal experience].
AB  - INTRODUCTION: Peritoneal carcinomatosis is the main problem in treating patients
      with advanced cancer; in addition to the lack demonstrably effective treatment,
      once diagnosed, this condition leads inexorably and rapidly to death. There is no
      response to traditional systemic treatments and the mean survival is less than 12
      months after diagnosis. The application of a new combined triple therapy
      consisting of cytoreductive surgery together with perioperative intraperitoneal
      chemotherapy and heated intraoperative intraperitoneal chemotherapy followed by
      early post-operative intra-abdominal chemotherapy is providing good results, even
      occasionally with curative intent, which suggests a new alternative treatment
      strategy. MATERIAL AND METHOD: We present our experience of a series of 110
      cytoreductions carried out by the author in 71 patients between February 14, 1997
      and February 14, 2007. RESULTS: In our series with a mean follow-up of 42 months,
      42% of the patients survived for more 18 months after treatment, 37% for over 2
      years, 20 % for more than 3 years, and 12.6% for over 5 years. Long-term survival
      was achieved among patients treated for persistent diffuse carcinomatosis
      secondary to pseudomyxoma, ovarian carcinomatosis, primary malignant peritoneal
      mesotheliomas, and colon carcinomatosis. CONCLUSIONS: The introduction and
      implementation of this new triple treatment strategy in Spain constitutes the
      best therapeutic alternative for these unfortunate patients. In our experience,
      we were able to achieve an initial control of the disease in 83% of our patients,
      medium-term survival (3 years) in 20% and long-term survival in 12.5% in four of
      the disease entities included in our protocol for the treatment of
      carcinomatosis.

PMID- 18053505
TI  - [Our experience of the clinical application of sentinel node biopsy in breast
      cancer].
AB  - INTRODUCTION: Systematical lymphadenectomy has been replaced by selective
      sentinel node biopsy in the initial staging of early breast cancer. The aim of
      this study was to assess the accuracy of the technique in its application phase,
      paying special attention to the follow-up of patients with negative sentinel node
      who did not undergo axillary lymphadenectomy. PATIENTS AND METHOD: A total of 168
      patients with 169 stage I and II breast cancer lesions underwent sentinel lymph
      node biopsy in its application phase. The procedure was previously validated by
      our group and included lymphoscintigraphy performed with periareolar or
      intratumoral injection of 99mTc stannous colloid, and radioguided surgical
      detection on the following day. RESULTS: Lymphoscintigraphic sentinel node
      localization was successful in 95.3% of the lesions (161/169) and axillary
      surgical detection in 90.5% (153/169), with 1.1 nodes excised per patient (range
      1-4). Malignancy was found in 30.1% of the sentinel nodes removed (46/153), 11 of
      which were micrometastases (23.9%). Subsequent axillary dissection revealed that
      the sentinel node was the only node involved in 22/46 (47.8%). The sentinel node
      was found to be negative in the remaining 107/153 lesions (69.9%), and surgical
      treatment was considered to be complete. To date, the mean follow-up of the
      patients has been 20.4 months (range 3-49), and no axillary recurrences have been
      observed. Of the entire group, four patients developed distant metastases; one
      had concomitant mammary recurrence and died. CONCLUSIONS: Application of sentinel
      node biopsy is safe and has improved our RESULTS: This technique allows correct
      staging and probably maintains local control of the disease.

PMID- 18053506
TI  - [Multifocal basaloid squamous carcinoma of the esophagus].
AB  - Basaloid-squamous carcinoma is a poorly-differentiated variety of squamous cell
      carcinoma. The most common location is the upper aerodigestive tract and the
      incidence of this entity in the esophagus is low. Despite advances in knowledge
      of the biology of these tumors, their recent description and their low frequency
      has hampered consensus on the therapeutic approach. We present a case of basaloid
      squamous cell of the esophagus a 54 year-old man who underwent an esophagectomy
      with lymphadenectomy and has been followed-up for 5 years with no evidence of
      disease recurrence. We also provide a literature review of this entity.

PMID- 18053507
TI  - [Esophageal duplication cyst as an unusual cause of adult dysphagia].
AB  - Esophageal duplication cyst is a rare congenital alteration. Most of these cysts
      are asymptomatic and are usually identified as an incidental finding. These
      lesions can develop complications (bleeding, infection, etc.) and even malignant
      degeneration. Consequently, the treatment of choice is surgical.

PMID- 18053508
TI  - [Pneumoperitoneum in polytraumatized patients without perforated hollow viscera].
AB  - Bowel and mesenteric injuries from blunt abdominal trauma are infrequent and
      difficult to diagnose. A finding of pneumoperitoneum on computed tomography is
      useful, although not specific. In associated blunt chest trauma gas can reach the
      peritoneal cavity through congenital or post-traumatic diaphragmatic
      interruptions. Two cases of pneumoperitoneum following associated blunt chest and
      abdominal trauma are reported. In both patients laparotomy did not show bowel
      perforation and conservative treatment could have been provided.

PMID- 18053509
TI  - [Mesenteric root abscess due to perforated jejunal diverticulum].

PMID- 18053510
TI  - [Fulminant pseudomembranous colitis].

PMID- 18053511
TI  - [Lumbar drainage of a giant retroperitoneal abscess secondary to necrotizing
      pancreatitis].

PMID- 18053512
TI  - [Pulmonary dirofilariasis. A cause of solitary pulmonary nodule].

PMID- 18053513
TI  - [Hemobilia: a rare cause of massive gastrointestinal bleeding].

PMID- 18053514
TI  - [Ileal metastasis from melanoma of unknown origin].

PMID- 18053515
TI  - [Clinical use of diagnostic laboratory tests in childhood sepsis].

PMID- 18053516
TI  - [Usefulness of procalcitonin as an early diagnostic test of neonatal sepsis in
      newborns with risk factors for infection].
AB  - OBJECTIVE: To investigate the reliability of serum procalcitonin (PCT) as an
      early diagnostic test (within the first 12 hours of life) of neonatal sepsis in
      newborns with maternal or neonatal risk factors for infection. MATERIAL AND
      METHODS: We performed a prospective study of 123 newborns consecutively admitted
      to neonatal unit over a 2-year period with at least one risk factor for
      infection. We constructed a 2x2 table between the validated test (serum PCT by
      semi-quantitative assay, with several cut-off points: 0.5, 2 and 10 ng/ml) and
      the reference assay (blood culture or clinical, laboratory and microbiological
      confirmation of sepsis). The validity (sensitivity, specificity), safety
      [positive predictive value (PPV) and negative predictive value (NPV)] and
      likelihood ratios (LR+ and LR-) of the test were calculated. RESULTS: Serum PCT
      was measured within the first 12 hours of life in 95% of the patients (mean and
      median=6 hours). The best cut-off point for serum PCT was 2 ng/ml, and, taking
      subsequent clinical-laboratory-microbiological confirmation of sepsis as the best
      reference assay, showed a sensitivity of 100% (95% CI 65-100), specificity of 82%
      (95% CI 74-88), PPV of 25% (95% CI 13-44), NPV of 100% (95% CI 96-100), LR+ of
      5.5 (95% CI 3.7-8.1), and LR- of 0. CONCLUSIONS: Serum PCT levels<2 ng/ml within
      the first 6-12 hours of life in newborns with risk factors for infection are
      useful as a screening assay to rule out neonatal sepsis with a sensitivity of
      100% (false negatives=0% and NPV=100%). However, for subsequent confirmation a
      more specific assay (with a low false positive rate and high PPV) should be used,
      such as C-reactive protein. The higher cost of the serum PCT test should be
      weighed against shorter admissions as a result of its use.

PMID- 18053517
TI  - [T lymphocyte immunophenotype as a diagnostic marker of late-onset neonatal
      sepsis].
AB  - BACKGROUND: Given the high risks associated with neonatal sepsis, there is a need
      for a diagnostic marker that would predict the disease before the results of
      blood or cerebrospinal fluid cultures are available. We evaluated changes in the
      CD4+ T lymphocyte immunophenotype in neonates with late-onset sepsis to try to
      improve the test combinations currently used (C reactive protein, immature:total
      neutrophil ratio, leukocytosis). PATIENTS AND METHODS: We performed a prospective
      cohort study in 24 neonates with late-onset sepsis and 48 non-infected controls
      with a gestational age of 37 weeks or less. CD4+ T lymphocyte subpopulations in
      peripheral blood samples were identified by labeling with monoclonal antibodies
      and quantified by flow cytometry. Diagnostic performance curves were constructed
      by logistic regression. RESULTS: As a marker of late-onset neonatal sepsis, a
      percentage of CD4+/CD45RO+/CD45RA- T lymphocytes of >3.5% showed a sensitivity of
      94.1%, specificity of 69.2%, positive predictive value of 80.0%, negative
      predictive value of 90.0%, and odds ratio of 36.0 (p<0.001). When we combined
      this marker with a C-reactive protein level of >10.0 mg/L, the specificity of
      this combination of tests increased to 94.7% and the positive predictive value to
      85.7%. CONCLUSIONS: A percentage of CD4+/CD45RO+/CD45RA- T lymphocytes of >3.5%
      is an effective indicator of late-onset neonatal sepsis in preterm infants. If
      this marker is combined with a C-reactive protein level of >10.0 mg/l, its
      diagnostic performance is improved.

PMID- 18053518
TI  - [Nosocomial Candida infections and thrombocytopenia in very low birth weight
      newborns].
AB  - OBJECTIVE: To analyze thrombocytopenia as an early marker of late-onset neonatal
      Candida sepsis and to determine whether there are significant differences in
      platelet count between neonates infected by different infectious agents. MATERIAL
      AND METHODS: We retrospectively reviewed the medical charts of 42 neonates with
      late-onset sepsis with positive blood culture in our neonatology service between
      January 1, 2003 and December 31, 2004. Only the first episode of sepsis in any
      single patient was included. The principal parameter examined was the incidence
      of thrombocytopenia according to the microorganisms causing the sepsis (Gram
      positive bacteria, Gram negative bacteria and fungi). The statistical analysis
      was performed using SPSS version 11.5. The data are expressed as mean+/-standard
      deviation. The chi-squared test was used to compare qualitative variables. For
      quantitative variables, the Kolmogorov-Smirnov was used; ANOVA was used for
      parametric variables and the Kruskal-Wallis test for non-parametric variables. A
      value of p<0.5 was considered significant. RESULTS: Late-onset sepsis was
      diagnosed in 42 (2.3%) of 1,757 newborn admissions. Gestational age at birth was
      31+/-4.9 weeks (24-41.5 weeks) with a mean birth weight of 1,618+/-911 g (750
      4,070 g). There were 34 boys (81%) and eight girls (19%). When patients infected
      with the three groups of microorganisms were compared, no significant differences
      were found except for birth weight, days of stay in the neonatal intensive care
      unit, thoracotomy, days of mechanical ventilation, antibiotic therapy before
      sepsis, and thrombocytopenia. Gram-positive sepsis was found in 47.6%, Gram
      negative sepsis in 33 % and fungal sepsis in 19%. The only cause of fungal sepsis
      was Candida, mainly C. glabrata (50%), followed by C. albicans (37.5%) and C.
      parapsilosis (12.5%). The most reliable marker of Candida sepsis was
      thrombocytopenia, which was found in 17.7% of the episodes of late-onset sepsis.
      The incidence of thrombocytopenia was significantly higher in Candida sepsis than
      in bacterial sepsis (100% vs 5.9%) (p<0.001). Only two patients with bacterial
      sepsis had thrombocytopenia and both cases were caused by Gram-negative bacteria.
      CONCLUSION: Thrombocytopenia is a highly specific marker of neonatal Candida
      sepsis. Analysis of platelet counts is a simple laboratory test that helps to
      guide diagnosis and the use of early empirical therapy.

PMID- 18053519
TI  - [Determination of normal acylcarnitine levels in a healthy pediatric population
      as a diagnostic tool in inherited errors of mitochondrial fatty acid beta
      oxidation].
AB  - INTRODUCTION: Acylcarnitine measurement in blood is a useful test for the
      diagnosis of inherited errors of mitochondrial fatty acid beta-oxidation.
      However, there are few data in the literature on the reference ranges of the
      various acylcarnitines and on whether these reference ranges are age- or sex
      dependent. OBJECTIVES: To draw attention to inherited errors of mitochondrial
      fatty acid beta-oxidation and to establish reference acylcarnitine values in
      children. PATIENTS AND METHODS: A total of 309 blood samples from healthy
      children divided into four age groups (group A: <1 month; group B: 1-12 months;
      group C: 1-7 years; group D: 7-18 years) were obtained and analyzed using tandem
      mass spectrometry. RESULTS AND CONCLUSION: Reference acylcarnitine values in
      children are provided. No significant differences were found in relation to age
      or sex. Our results differ from those reported in the literature reviewed.
      Importantly, hydroxyacylcarnitines and glutaryl carnitine are absent when normal
      samples are processed. We review the literature on the main clinical and
      laboratory findings in mitochondrial fatty acid beta-oxidation deficiencies.

PMID- 18053520
TI  - [Severe thoracic trauma: review of 39 cases].
AB  - OBJECTIVE: To study the incidence and types of severe thoracic trauma in a cohort
      of pediatric polytrauma patients, compare cardiac contractility between patients
      with elevated troponin T levels and those with abnormal electrocardiogram (EKG)
      findings, and to analyze the value of thoracic computed tomography (CT) scan as a
      first investigation in patients with suspected thoracic trauma. MATERIAL AND
      METHODS: We performed a 5-year retrospective study in a cohort of trauma patients
      with an injury severity score of >or=25. Thoracic trauma included pulmonary
      contusion, hemopneumothorax, large-vessel injury, myocardial contusion, and rib
      fracture. In all patients, EKG and determination of troponin T were performed at
      admission. Echocardiogram was performed in patients with troponin T levels>0.035
      U/L (except in two patients, because the technique was not available) and
      abnormal EKG findings. A thoracic CT scan was performed in unconscious patients
      or when thoracic trauma was clinically suspected, as well as a simple thorax X
      ray in the following 24 hours. RESULTS: Among 209 multiple-trauma patients,
      thoracic injuries where detected in 39 patients. The most frequent injury was
      pulmonary contusion. Echocardiogram was performed in 10 patients with high
      troponin levels, with abnormal findings in eight patients. The six patients with
      EKG alterations also had high troponin levels and pathological findings on
      echocardiogram. Thoracic CT scan was performed in 81 patients, with abnormal
      findings in 36 patients. Thoracic lesions were observed in simple X-ray in three
      patients who had not undergone CT scan. CONCLUSIONS: The most frequent thoracic
      trauma was pulmonary contusion. The results of echocardiogram were abnormal in 80
      % of the patients with high troponin levels who underwent this examination.
      Thoracic CT scan was highly useful in suspected thoracic trauma.

PMID- 18053521
TI  - [Lung function and exposure to tobacco smoke among adolescents].
AB  - OBJECTIVE: To study lung function in adolescents in relation to smoking (active
      and passive smokers) and to investigate the repercussion on spirometric
      parameters. PATIENTS AND METHOD: We studied 301 healthy adolescents with no
      history of bronchial asthma or colds in the month prior to the study. A
      questionnaire on tobacco exposure was administered and spirometry (Datospir-92)
      was performed. RESULTS: There were 165 boys (54.5%) and 136 girls (45.5%) aged
      between 14 and 20 years old (16.40+/-1.32). A total of 27.2% were non-smokers and
      were not exposed to tobacco smoke (NS), 31.3% were passive smokers, with
      household exposure of 10 cigarettes per day during at least the previous year
      (PS), and 41.5% were current smokers who had been smoking>or=10 cigarettes/day
      for at least 1 year (CS). Significant differences were found between age and
      smoking habits (p=0.0001) and between smoking habits and female sex (girls CS:
      33.9% vs boys CS: 21.8 %) (p=0.007). A significant association was found between
      smoking (NS, PS and CS) and spirometric parameters (ANOVA): forced vital capacity
      (FVC) (p=0.001), forced expiratory volume in 1 second (FEV1) (p=0.0001), FEV1/FVC
      (p=0.004), peak expiratory flow (PEF) (p=0.0001), midexpiratory flow at 25% of
      forced vital capacity (MEF25%) (p=0.01), MEF50% (p=0.0001) and MEF25-75%
      (p=0.0001); CS in relation to NS was as follows: FEV1, PEF, MEF50%, MEF25-50%
      (p=0.0001) and FVC, FEV1/FVC, MEF25% (p=0.01); CS in relation to PS: FEV1/ FVC
      (p=0.02), PEF (p=0.004), MEF50% and MEF25-75% (p=0.003), PS in relation to NS:
      FVC and FEV1 (p=0.02). Significant differences in FVC, FEV1 and MEF25-75% were
      found in female CS in comparison with boys. CONCLUSIONS: The CS group showed a
      significant decrease in spirometric parameters in relation to the NS group. The
      airway was affected sooner in the female group of smokers than in the male group,
      even though the intensity and time of exposure were the same in both groups.

PMID- 18053522
TI  - [Values of high-density lipoprotein cholesterol in the pediatric population and
      risk of thrombosis].
AB  - INTRODUCTION: There is evidence of the protective effect of high-density
      lipoprotein (HDL)-cholesterol against atheroma plaque formation and of its role
      in cholesterol efflux from cells, as well as its anti-oxidative and inflammatory
      modulating response properties. Low HDL-cholesterol levels have been associated
      with a prothrombotic state. OBJECTIVE: To determine the relationship between HDL
      cholesterol and lipidic and hemostatic parameters. PATIENTS AND METHODS: We
      studied 110 children (50 girls, 60 boys) aged between 6 and 7 years old. Lipid
      profile, D-dimer, plasminogen activator inhibitor (PAI) and fibrinogen were
      determined. RESULTS: The mean values of the studied parameters were as follows:
      total cholesterol (192.92+/-26.01 mg/dl), HDL-cholesterol (72.87+/-15.69 mg/dl),
      low-density lipoprotein-cholesterol (109.46+/-23.30 mg/dl), triglycerides
      (56.24+/-20.35 mg/dl), apolipoprotein B (91.96+/-14.93 mg/dl), apolipoprotein A1
      (168.4+/-24.55 mg/dl), lipoprotein(a) logarithm (1.76+/-1.36 mg/dl), plasminogen
      activator inhibitor-1 logarithm (PAI-1) (3.77+/-3.93 U/ml), D-dimer logarithm
      (5.53+/-0.49 ng/ml) and fibrinogen (268.61+/-48.59 mg/dl). When the sample was
      divided into two groups according to HDL-cholesterol levels, children with lower
      levels showed significantly higher values of total cholesterol/HDL-cholesterol,
      fibrinogen and PAI. HDL-cholesterol levels were directly and significantly
      associated with total cholesterol and apolipoprotein A1 and negatively and
      significantly associated with the total cholesterol/HDL-cholesterol ratio,
      fibrinogen and PAI. CONCLUSION: The children studied had high HDL-cholesterol
      levels, which could be responsible for the high total cholesterol levels. High
      values of HDL-cholesterol are significantly associated with a reduction in
      thrombotic risk.

PMID- 18053523
TI  - [Agreement between two devices for measuring exhaled nitric oxide].
AB  - BACKGROUND: Measurement of fractional exhaled nitric oxide (FENO) is a non
      invasive marker of eosinophilic airway inflammation that can be useful in asthma
      diagnosis and control, as well as in treatment monitoring. OBJECTIVE: We studied
      the correlation between two techniques for measuring FENO: the chemiluminescence
      based analyzer (NIOX, Aerocrine, Sweden) and a new portable electrochemical
      sensor-based analyzer (NIOX-MINO, Aerocrine). MATERIAL AND METHODS: FENO was
      measured by the single breath on-line method. In all children, three consecutives
      measurements were obtained with NIOX, with a maximum of six attempts, and the
      arithmetic mean was calculated. Next, using NIOX-MINO, a single measurement was
      made successively in each of the children. The variables analyzed were sex, age,
      height, weight, diagnosis, treatment, NIOX-MINO value, mean of three values
      obtained with NIOX and the NO elimination rate (nL/min). For the statistical
      analysis, the Bland-Altman plot was used to compare the means and the differences
      between measurements of FENO from NIOX and NIOX-MINO. The agreement between the
      two analyzers was estimated by Cohen's Kappa statistic. RESULTS: Thirty children
      were included, 14 (46.67%) boys and 16 (53.33%) girls. The mean age was 11.3+/
      3.09 years. All of the children successfully performed the measurements with two
      analyzers. The relationship between the means and the differences in the values
      obtained with NIOX-MINO and NIOX were statistically significant (p<0.005). In
      addition, Cohen's Kappa statistic (0.78) suggested a high degree of agreement
      between the results obtained with the two devices. CONCLUSIONS: The two
      analyzers, NIOX-MINO and NIOX, were not equivalent. There was good agreement
      between the FENO values measured with the two devices. Measurement of FENO with
      the portable electrochemical sensor-based analyzer (NIOX-MINO) is valid and
      feasible in children older than 5 years.

PMID- 18053524
TI  - [Pyomyositis in children: not only a tropical disease].
AB  - INTRODUCTION: Pyomyositis is an acute bacterial infection of skeletal striated
      muscle typical of tropical countries but infrequent in our environment. The
      present review aims to describe the clinical characteristics, epidemiology,
      etiology, diagnosis and outcome of patients with pyomyositis in our hospital.
      MATERIAL AND METHODS: The medical records of patients diagnosed with pyomyositis
      in our hospital from 2002 to 2005 were reviewed. Epidemiological, clinical, and
      microbiological data as well as the diagnostic tests and treatment strategies
      used were gathered and a descriptive analysis was performed. RESULTS: There were
      seven patients (five boys and two girls). The mean age of the patients was 8.6
      years. Five patients (70%) presented during the 6 warmer months. There were four
      secondary cases (one HIV infection, three musculoskeletal injuries). The most
      frequent sites were the psoas-iliac region and thigh. The main symptoms at
      presentation were pain and fever. The most common diagnostic imaging modality was
      ultrasound examination, although magnetic resonance imaging had the highest
      diagnostic yield (sensitivity of 100% versus 33% for ultrasound). The most
      prevalent microorganism in our series was Staphylococcus aureus (found in three
      out of seven patients). Only two abscesses were surgically drained and the
      remainder were treated with antibiotics alone, first intravenously (mean of 17
      days) and then orally (mean of 26 days). None of our patients developed sequelae.
      CONCLUSIONS: Pyomyositis should be included in the differential diagnosis in
      children with fever, pain and/or functional impotence, even though this entity is
      infrequent in our environment. The most sensitive diagnostic test is magnetic
      resonance imaging. With early diagnosis and correct treatment, outcome is good.

PMID- 18053525
TI  - [Pyroglutamic acidemia associated with acetaminophen].
AB  - We report a case of pyroglutamic acidemia probably related to acetaminophen
      administration. A 16-month boy recovering from hemolytic uremic syndrome abruptly
      developed unexplained high anion gap metabolic acidosis requiring hemodialysis.
      Septic shock, lactic acidosis and salicylate intoxication were ruled out.
      Betahydroxybutyrate and acetoacetate levels were within the normal range. No
      osmolarity gap or high amino acid levels were found. Urine and blood pyroglutamic
      acid levels were 392 mmol/mol creatinine (reference range: 9-55) and 9.8 mmol/L
      (reference range<0.16), respectively. The patient was receiving acetaminophen. We
      conclude that pyroglutamic acidosis should be considered in patients receiving
      acetaminophen who abruptly develop high anion gap metabolic acidosis not
      attributable to more common causes.

PMID- 18053526
TI  - [Should pulmonary computed tomography be performed in children with tuberculosis
      infection without apparent disease?].
AB  - BACKGROUND: During early childhood, in particular, there is a continuum between
      tuberculosis infection and disease. When establishing the diagnosis in a child
      with suspected tuberculosis, the distinction between infection and disease
      frequently depends on the interpretation of the chest X-ray. Some studies have
      shown hilar and mediastinal lymphadenopathies on computed tomography (CT) in
      children with tuberculosis infection without apparent disease, i.e., asymptomatic
      children with a positive tuberculin skin test and normal chest X-ray. These
      observations raise the issue of whether pulmonary CT should be performed in
      children with tuberculosis infection without apparent disease and whether
      different types of therapy should be administered depending on the results.
      METHODS: We reviewed the physiopathology of tuberculosis infection and disease,
      diagnostic methods and treatment, and the literature on the use of pulmonary CT
      scan in pediatric tuberculosis. RESULTS: Modern CT scanners indicate hilar and
      mediastinal lymphadenopathies in many of the children with tuberculosis infection
      with no apparent disease on chest X-rays. However, neither the size nor the
      morphology of these adenopathies allows active tuberculosis to be diagnosed. The
      natural history of childhood tuberculosis indicates that most children show hilar
      lymphadenopathies after the primary infection, although progression to disease is
      rare and is characterized by the presence of clinical symptoms. The exceptions
      are children younger than 4 years old and those with immune alterations who more
      frequently show progression of infection to disease and who require close follow
      up. In addition, the experience accumulated over many years in the treatment of
      tuberculosis infection with isoniazid has shown this drug to be effective in both
      short- and long-term prevention of active disease. Official guidelines and expert
      opinion do not recommend systematic pulmonary CT scan in these children or
      modification of treatment according to the results. CONCLUSIONS: Hilar and
      mediastinal lymph nodes are frequently found in the CT scans of children with
      tuberculosis infection without apparent disease but there is no evidence that
      these adenopathies indicate active disease or that these children require
      different treatment. Consequently, until demonstrated otherwise, pulmonary CT
      scanning and changes in chemoprophylaxis are not justified in children with
      tuberculosis infection.

PMID- 18053527
TI  - [Review of standards and recommendations for the design of a neonatology unit].
AB  - Standards for the design of a neonatology unit are reviewed. The process should
      begin with a planning team to outline the desired objectives to be achieved,
      followed by the intervention of a team of architects. Medical considerations,
      standards and recommendations, as well as architectural considerations (adequate
      privacy and intimacy, need for social support and communication, flexibility and
      accessibility) should be taken into account. From the architectural point of
      view, the greatest problem is the space available; furthermore, if the aim is to
      personalize the unit for the newborn and family, the need for space will be even
      greater. The following aspects should be analyzed and integrated into the design
      of the unit: standards and recommendations regarding space, the site of the unit,
      area of direct neonatal care, electrical installation, equipment, lighting and
      noise levels, nursing staff, communication systems, maintenance and
      refurbishment.

PMID- 18053528
TI  - [Neonatal sepsis due to Eikenella corrodens].

PMID- 18053529
TI  - [Epidemiology and clinical findings in late-onset neonatal sepsis in the
      pediatric intensive care unit].

PMID- 18053530
TI  - [Resolution of intracardiac thrombi with local low dose urokinase in an extremely
      low birth weight premature infant].

PMID- 18053531
TI  - [Langer's type mesomelic dysplasia].

PMID- 18053532
TI  - [Necrotizing gastritis].

PMID- 18053533
TI  - [Scintigraphic pattern of dumping syndrome].

PMID- 18053534
TI  - [Beau's lines and Kawasaki disease].

PMID- 18053535
TI  - [Cavernomatous malformation of the portal vein].

PMID- 18053536
TI  - [Domiciliary invasive mechanical ventilation: the parents' perspective].

PMID- 18053537
TI  - [Simple abdominal X-ray as a diagnostic method in abdominal pain. Diagnosis:
      mature teratoma in ovarian torsion].

PMID- 18053538
TI  - [Hypertension and white coffee stains. Diagnosis: aorta media syndrome associated
      with type 1 neurofibromatosis].

PMID- 18053539
TI  - [Inhaled insulin and its effects on the lungs].

PMID- 18053540
TI  - [Childhood asthma: do the answers coincide with the questions?].

PMID- 18053541
TI  - [Agreement between oxygen desaturation index and apnea-hypopnea index in adults
      with suspected obstructive sleep apnea at an altitude of 2240 m].
AB  - OBJECTIVE: Altitude can affect the diagnostic accuracy of portable monitors used
      to diagnose suspected obstructive sleep apnea syndrome on the basis of oxygen
      desaturation measurements. The aim of this study was to determine agreement
      between the desaturation index measured by oximetry and the apnea-hypopnea index
      measured by polysomnography in Mexico City (2240 m above sea level). We also
      wished to determine agreement between the desaturation index and the respiratory
      disturbance index measured by monitoring airflow with a single-channel recording
      device. PATIENTS AND METHODS: We used standard polysomnography and nocturnal
      oximetry to simultaneously measure the apnea-hypopnea index and the desaturation
      index, respectively, in a group of 38 patients aged over 18 years with suspected
      obstructive sleep apnea syndrome. In a second group of 30 patients, we compared
      the desaturation index to the respiratory disturbance index, which we measured
      using a single-channel device monitoring nasal airflow. RESULTS: The mean (SD)
      intraclass correlation coefficient between the apnea-hypopnea index and the
      desaturation index was 0.89 (0.03) (95% confidence interval, 0.83-0.96), and the
      mean of the differences was -0.9 (14.2). The mean intraclass correlation
      coefficient for the desaturation index and the respiratory disturbance index was
      0.93 (0.02) (95% confidence interval, 0.89-0.97), and the mean of the differences
      was -6.6 (8.3). CONCLUSIONS: Agreement was high between the desaturation index
      and both the apnea-hypopnea index and the respiratory disturbance index in adults
      with suspected obstructive sleep apnea syndrome in Mexico City.

PMID- 18053542
TI  - [Sleep apnea-hypopnea syndrome in a pediatric population: differences between
      children with tonsillar hypertrophy and those with concomitant disease].
AB  - OBJECTIVE: Our aim was to compare clinical and polysomnographic variables in
      pediatric patients with sleep apnea-hypopnea syndrome (SAHS) secondary to
      tonsillar hypertrophy with those in patients with concomitant disease. PATIENTS
      AND METHODS: We studied 42 children with SAHS (mean [SD] age, 8 [4] years; body
      mass index [BMI], 19.6 [5.2] kg/m2; neck circumference, 29 [4] cm; and BMI
      percentile, 67 [36]), 26 of whom were otherwise healthy (group A) and 16 of whom
      had concomitant disease (group B). RESULTS: A comparison of groups A and B showed
      no significant differences in age (7.7 [3.9] years vs 8.4 [3.9] years; P=not
      significant [NS]); sex, BMI (17.6 [4] kg/m2 vs 20.4 [6] kg/m2; P=NS), neck
      circumference (29.3 [4.7] cm vs 30.7 [3.5] cm; P=NS), or BMI percentile (61 [37]
      vs 76 [34]; P=NS). Tonsillar hypertrophy was more frequent in group A (P=.02) and
      craniofacial abnormalities (P=.008), macroglossia (P=.04), and dolichocephalia
      (P=.04) were more frequent in group B. No significant differences were observed
      in neurophysiologic variables or in the respiratory disturbance index, although
      group A presented higher oxygen saturation levels (97 [1.7] vs 95 [2]; P< .007),
      lower oxygen desaturation index scores (7 [7] vs 15 [10]; P=.007), and a lower
      cumulative percentage of time with oxygen saturation lower than 90% (2.2 [4] vs
      16.4 [4]; P=.01). Twenty-three patients (88.5%) in group A underwent
      tonsillectomies compared to 7 (44%) patients in group B (P=.003). Seven patients
      (44%) in group B were treated with continuous positive airway pressure (CPAP) and
      2 patients were treated with bi-level positive airway pressure (BiPAP), compared
      to 1 patient (3.8%) treated with CPAP in group A (P=.003). Three children in
      group B underwent maxillary surgery. The evolution of clinical and polygraphic
      variables was more favorable in group A (P=.04). CONCLUSIONS: Children with SAHS
      suffer from repeated infections, delayed weight gain, hyperactivity, and
      neuropsychiatric manifestations. Obesity (associated with concomitant disease)
      and sleepiness are uncommon. Although most patients require surgery, as many as a
      third require treatment with CPAP or BiPAP. Furthermore, children with SAHS and
      concomitant disease show no specific clinical characteristics, although they tend
      to be more obese, have more craniofacial abnormalities, and greater nocturnal
      hypoventilation.

PMID- 18053543
TI  - [Discriminative properties and validity of a health status questionnaire in
      obstructive airway disease patients: the Airway Questionnaire 20].
AB  - OBJECTIVE: To evaluate the discriminative properties and validity of the Airways
      Questionnaire 20 (AQ20) in a sample of patients with airway obstruction and to
      compare its properties with those of the St George's Respiratory Questionnaire
      (SGRQ) and the Short Form 36 (SF-36). PATIENTS AND METHODS: A convenience sample
      of 47 subjects was recruited from among 61 consecutive patients referred to an
      outpatient clinic specialized in obstructive airway diseases. All subjects
      completed the AQ20, SGRQ, and SF-36. Other measures were the baseline dyspnea
      index (BDI), 6-minute walk test (6MWT) distance, spirometry, results of arterial
      blood gas analysis, and body mass index. RESULTS: The AQ20 showed very good
      correlation with the SGRQ total score (rho=0.84, P< .001) and moderate
      correlation with all SF-36 domains (physical capacity, rho=-0.53; physical
      functioning, rho=-0.61; bodily pain, rho=-0.55; general health, rho=-0.59;
      vitality, rho=-0.55; social functioning, rho=-0.57; emotional role functioning,
      rho=-0.51; mental health, rho=-0.61; all P< .001). The BDI and the 6MWT distance
      were the best predictors of AQ20 score (r2=0.31) in the regression model. An area
      under the receiver operating characteristic curve of 0.91 (P< .001) indicated a
      high level of accuracy for the AQ20, using the SGRQ as the gold standard.
      CONCLUSION: This study shows that the AQ20 is an accurate health status
      questionnaire in patients with moderate-to-severe airway obstruction. It could be
      an alternative to longer, traditional questionnaires such as the SGRQ.

PMID- 18053544
TI  - [Results of smoking cessation therapy in a specialist unit].
AB  - OBJECTIVE: The aim of this study was to assess the results of smoking cessation
      therapy in a specialist unit by calculating the probability of continued
      abstinence at 6-month follow-up and analyzing differences according to the
      characteristics of the individuals. PATIENTS AND METHODS: A prospective
      longitudinal study was undertaken in smokers who received multicomponent smoking
      cessation therapy over a period of 3 months. Continued abstinence was assessed on
      the basis of self-report by participants and confirmed by measurement of exhaled
      carbon monoxide levels. Kaplan-Meier survival analysis was performed to assess
      the probability of continued abstinence. Log-rank tests were used to analyze
      differences in continued abstinence according to different qualitative variables.
      RESULTS: The 1120 patients who participated in the study (56% men and 44% women)
      had a mean (SD) age of 44.1 (9.5) years. The mean score on the Fagerstrom test
      was 6.3 (2.1). Nicotine replacement therapy was provided in 70.8% of patients
      while 29.2% received bupropion. The probability of continued abstinence at 6
      months was 62.2%. Individuals with a high dependence had a lower probability of
      continued abstinence at 6 months, as did those in whom treatment adherence was
      poor. No differences were observed in the probability of abstinence according to
      sex or type of pharmacological treatment. CONCLUSIONS: Individuals with a high
      nicotine dependence can benefit from intensive smoking-cessation treatment in a
      specialist unit to achieve continued abstinence.

PMID- 18053545
TI  - [Design of a lung simulator for teaching lung mechanics in mechanical
      ventilation].
AB  - Over the last 10 years, noninvasive ventilation has become a treatment option for
      respiratory insufficiency in pulmonology services. The technique is currently
      included in pulmonology teaching programs. Physicians and nurses should
      understand the devices they use and the interaction between the patient and the
      ventilator in terms of respiratory mechanics, adaptation, and synchronization. We
      present a readily assembled lung simulator for teaching purposes that is
      reproducible and interactive. Based on a bag-in-box system, this model allows the
      concepts of respiratory mechanics in mechanical ventilation to be taught simply
      and graphically in that it reproduces the patterns of restriction, obstruction,
      and the presence of leaks. It is possible to demonstrate how each ventilation
      parameter acts and the mechanical response elicited. It can also readily simulate
      asynchrony and demonstrate how this problem can be corrected.

PMID- 18053546
TI  - [Prognostic factors in chronic obstructive pulmonary disease].
AB  - Efforts over the last few decades to extend the life expectancy of patients with
      chronic obstructive pulmonary disease (COPD) have faced difficulties, but our
      perception of the problems involved is now starting to change. Improvements in
      our understanding of the pathogenic and etiological mechanisms of the disease,
      analysis of the causes of death, and, in particular, identification of the
      relevant prognostic factors have resulted in firm advances that allow us to face
      the future with greater optimism. The aim of this review is to provide a detailed
      analysis of the chief prognostic factors described in the literature and to
      evaluate the therapeutic implications of these findings. The traditional view
      maintained that the accelerated decline in forced expiratory volume in 1 second
      over time was one of the best predictors of mortality, and this belief has for
      decades determined the strategies used to treat COPD. However, we now know COPD
      to be a multidimensional disease and are aware that some of its other
      manifestations have important prognostic implications. Lung hyperinflation,
      exercise tolerance, exacerbations, comorbidity, and systemic manifestations-in
      particular those related to the cardiovascular system-have all been shown in
      recent years to be strong predictors of mortality. The inflammatory substrate,
      whether local or systemic, merits special consideration because it appears to be
      the cause of many of these manifestations. These newly identified prognostic
      factors are of great interest in that it may be possible to moderate their
      influence, a circumstance that highlights the need to change the traditional
      treatment approach and devise therapeutic interventions oriented towards
      reversing the effects of these factors.

PMID- 18053547
TI  - [Balloon dilatation of the trachea as treatment for idiopathic tracheal
      stenosis].
AB  - The treatment of choice for idiopathic tracheal stenosis is tracheal resection
      and anastomosis, although some authors prefer more conservative management.
      Between January 1, 1996 and January 1, 2005, 8 patients-all women-with idiopathic
      tracheal stenosis were treated in the chest surgery department of the Hospital
      Universitario La Fe in Valencia, Spain. One case was treated by means of surgery
      and so was excluded from this study. The remaining 7 women were treated by
      tracheal balloon dilatation; 4 required just 1 dilatation (and remained
      asymptomatic), 2 required 2 dilatations, and 1 required 4 dilatations. The median
      symptom-free interval was 25.5 months, and there was no associated mortality or
      morbidity. We conclude that balloon dilatation, which was not associated with
      mortality or morbidity, is a suitable treatment option for idiopathic tracheal
      stenosis.

PMID- 18053548
TI  - [Mediastinal panniculitis].

PMID- 18053549
TI  - [No evidence of a link between household radon concentrations and lung cancer in
      Cantabria, Spain].

PMID- 18053560
TI  - HIV/AIDS in Europe: epidemiological situation in 2006 and a new framework for
      surveillance.

PMID- 18053561
TI  - Chikungunya in north-eastern Italy: a summing up of the outbreak.

PMID- 18053562
TI  - An overview of Aedes aegypti and Aedes albopictus control in the British Overseas
      Territory of the Cayman Islands.

PMID- 18053563
TI  - 'The Disease Detectives' : a comic perspective on outbreak investigations.

PMID- 18053564
TI  - Outbreak of norovirus gastroenteritis among staff at a hospital in Barcelona,
      Spain, September 2007.

PMID- 18053565
TI  - European Monitoring Centre for Drugs and Drug Addiction annual report 2007:
      positive assessment of HIV in IDUs though hepatitis C still very high.

PMID- 18053566
TI  - A cluster of measles cases in northern Italy: a preliminary report.

PMID- 18053567
TI  - Contact tracing following exposure to measles at a wedding party in the United
      Kingdom, October 2007.

PMID- 18053568
TI  - A Dutch case of atypical pneumonia after culling of H5N1 positive ducks in
      Bavaria was found infected with Chlamydophila psittaci.

PMID- 18053569
TI  - Outbreak of Salmonella Weltevreden infections in Norway, Denmark and Finland
      associated with alfalfa sprouts, July-October 2007.

PMID- 18053570
TI  - HealthMap: the development of automated real-time internet surveillance for
      epidemic intelligence.
AB  - With the recent entry into force of the new International Health Regulations (IHR
      2005), there is still significant concern as to whether broad compliance will be
      feasible given the challenges associated with reporting mechanisms and
      multilateral coordination.

PMID- 18053571
TI  - Norovirus outbreak associated with canteen salad in Suffolk, United Kingdom.

PMID- 18053572
TI  - The EADGENE Microarray Data Analysis Workshop (open access publication).
AB  - Microarray analyses have become an important tool in animal genomics. While their
      use is becoming widespread, there is still a lot of ongoing research regarding
      the analysis of microarray data. In the context of a European Network of
      Excellence, 31 researchers representing 14 research groups from 10 countries
      performed and discussed the statistical analyses of real and simulated 2-colour
      microarray data that were distributed among participants. The real data consisted
      of 48 microarrays from a disease challenge experiment in dairy cattle, while the
      simulated data consisted of 10 microarrays from a direct comparison of two
      treatments (dye-balanced). While there was broader agreement with regards to
      methods of microarray normalisation and significance testing, there were major
      differences with regards to quality control. The quality control approaches
      varied from none, through using statistical weights, to omitting a large number
      of spots or omitting entire slides. Surprisingly, these very different approaches
      gave quite similar results when applied to the simulated data, although not all
      participating groups analysed both real and simulated data. The workshop was very
      successful in facilitating interaction between scientists with a diverse
      background but a common interest in microarray analyses.

PMID- 18053573
TI  - Analysis of the real EADGENE data set: comparison of methods and guidelines for
      data normalisation and selection of differentially expressed genes (open access
      publication).
AB  - A large variety of methods has been proposed in the literature for microarray
      data analysis. The aim of this paper was to present techniques used by the
      EADGENE (European Animal Disease Genomics Network of Excellence) WP1.4
      participants for data quality control, normalisation and statistical methods for
      the detection of differentially expressed genes in order to provide some more
      general data analysis guidelines. All the workshop participants were given a real
      data set obtained in an EADGENE funded microarray study looking at the gene
      expression changes following artificial infection with two different mastitis
      causing bacteria: Escherichia coli and Staphylococcus aureus. It was reassuring
      to see that most of the teams found the same main biological results. In fact,
      most of the differentially expressed genes were found for infection by E. coli
      between uninfected and 24 h challenged udder quarters. Very little
      transcriptional variation was observed for the bacteria S. aureus. Lists of
      differentially expressed genes found by the different research teams were,
      however, quite dependent on the method used, especially concerning the data
      quality control step. These analyses also emphasised a biological problem of
      cross-talk between infected and uninfected quarters which will have to be dealt
      with for further microarray studies.

PMID- 18053574
TI  - Analysis of the real EADGENE data set: multivariate approaches and post analysis
      (open access publication).
AB  - The aim of this paper was to describe, and when possible compare, the
      multivariate methods used by the participants in the EADGENE WP1.4 workshop. The
      first approach was for class discovery and class prediction using evidence from
      the data at hand. Several teams used hierarchical clustering (HC) or principal
      component analysis (PCA) to identify groups of differentially expressed genes
      with a similar expression pattern over time points and infective agent (E. coli
      or S. aureus). The main result from these analyses was that HC and PCA were able
      to separate tissue samples taken at 24 h following E. coli infection from the
      other samples. The second approach identified groups of differentially co
      expressed genes, by identifying clusters of genes highly correlated when animals
      were infected with E. coli but not correlated more than expected by chance when
      the infective pathogen was S. aureus. The third approach looked at differential
      expression of predefined gene sets. Gene sets were defined based on information
      retrieved from biological databases such as Gene Ontology. Based on these
      annotation sources the teams used either the GlobalTest or the Fisher exact test
      to identify differentially expressed gene sets. The main result from these
      analyses was that gene sets involved in immune defence responses were
      differentially expressed.

PMID- 18053575
TI  - Analysis of a simulated microarray dataset: comparison of methods for data
      normalisation and detection of differential expression (open access publication).
AB  - Microarrays allow researchers to measure the expression of thousands of genes in
      a single experiment. Before statistical comparisons can be made, the data must be
      assessed for quality and normalisation procedures must be applied, of which many
      have been proposed. Methods of comparing the normalised data are also abundant,
      and no clear consensus has yet been reached. The purpose of this paper was to
      compare those methods used by the EADGENE network on a very noisy simulated data
      set. With the a priori knowledge of which genes are differentially expressed, it
      is possible to compare the success of each approach quantitatively. Use of an
      intensity-dependent normalisation procedure was common, as was correction for
      multiple testing. Most variety in performance resulted from differing approaches
      to data quality and the use of different statistical tests. Very few of the
      methods used any kind of background correction. A number of approaches achieved a
      success rate of 95% or above, with relatively small numbers of false positives
      and negatives. Applying stringent spot selection criteria and elimination of data
      did not improve the false positive rate and greatly increased the false negative
      rate. However, most approaches performed well, and it is encouraging that widely
      available techniques can achieve such good results on a very noisy data set.

PMID- 18053576
TI  - Interval mapping of quantitative trait loci with selective DNA pooling data.
AB  - Selective DNA pooling is an efficient method to identify chromosomal regions that
      harbor quantitative trait loci (QTL) by comparing marker allele frequencies in
      pooled DNA from phenotypically extreme individuals. Currently used single marker
      analysis methods can detect linkage of markers to a QTL but do not provide
      separate estimates of QTL position and effect, nor do they utilize the joint
      information from multiple markers. In this study, two interval mapping methods
      for analysis of selective DNA pooling data were developed and evaluated. One was
      based on least squares regression (LS-pool) and the other on approximate maximum
      likelihood (ML-pool). Both methods simultaneously utilize information from
      multiple markers and multiple families and can be applied to different family
      structures (half-sib, F2 cross and backcross). The results from these two
      interval mapping methods were compared with results from single marker analysis
      by simulation. The results indicate that both LS-pool and ML-pool provided
      greater power to detect the QTL than single marker analysis. They also provide
      separate estimates of QTL location and effect. With large family sizes, both LS
      pool and ML-pool provided similar power and estimates of QTL location and effect
      as selective genotyping. With small family sizes, however, the LS-pool method
      resulted in severely biased estimates of QTL location for distal QTL but this
      bias was reduced with the ML-pool.

PMID- 18053577
TI  - Predicting the consequences of selecting on PrP genotypes on PrP frequencies,
      performance and inbreeding in commercial meat sheep populations.
AB  - Selection programmes based on prion protein (PrP) genotypes are being implemented
      for increasing resistance to scrapie. Commercial meat sheep populations
      participating in sire-referencing schemes were simulated to investigate the
      effect of selection on PrP genotypes on ARR and VRQ allele frequencies,
      inbreeding and genetic gain in a performance trait under selection. PrP selection
      strategies modelled included selection against the VRQ allele and in favour of
      the ARR allele. Assuming realistic initial PrP frequencies, selection against the
      VRQ allele had a minimal impact on performance and inbreeding. However, when
      selection was also in favour of the ARR allele and the frequency of this allele
      was relatively low, there was a loss of up to three to four years of genetic gain
      over the 15 years of selection. Most loss in gain occurred during the first five
      years. In general, the rate of inbreeding was reduced when applying PrP
      selection. Since animals were first selected on their PrP genotype before being
      selected on the performance trait, the intensity of selection on performance was
      weaker under PrP selection (compared with no PrP selection). Eradication of the
      VRQ allele or fixation of the ARR allele within 15 years of selection was
      possible only with PrP selection targeting all breeding animals.

PMID- 18053578
TI  - A new erythrose 4-phosphate dehydrogenase coupled assay for transketolase.
AB  - The standard assay for transketolase (E.C 2.2.1.1) has depended upon the use of D
      xylulose 5-phosphate as the ketose donor substrate since the production of D
      glyceraldehyde 3-phosphate can be readily coupled to a reaction that consumes
      NADH allowing the reaction to be followed spectrophotometrically. Unfortunately,
      commercial supplies of D-xylulose 5-phosphate recently became unavailable. In
      this article we describe the coupling of a transketolase reaction (using
      Leishmania mexicana transketolase) that converts D-fructose 6-phosphate to D
      erythrose 4-phosphate. D-Erythrose 4-phosphate can then be converted to 4
      phosphate D-erythronate using erythrose-4-phosphate dehydrogenase (E.C 1.2.1.72),
      a reaction that reduces NAD+ to NADH and can be easily followed
      spectrophotometrically. D-Ribose 5-phosphate and D-glyceraldehyde 3-phosphate can
      both be used as ketol acceptor substrates in the reaction although D-ribose 5
      phosphate is also a substrate for the coupling enzyme.

PMID- 18053579
TI  - Reliability of quantitative EMG analysis of the extensor carpi radialis muscle.
AB  - This study investigated the within-subject, intra- and inter-operator reliability
      of quantitative electromyographic (EMG) analysis using decomposition-based
      quantitative electromyography (DQEMG). Needle and surface-detected EMG signals
      were collected during low-level isometric contractions of the extensor carpi
      radialis (ECR) muscle. DQEMG was used to extract needle-detected motor unit
      potential (MUP) trains and surface-detected MUPs (SMUPs) associated with each
      train. Two independent experienced operators re-decomposed and processed the MUP
      data on two separate occasions. One-way analyses of variance (ANOVA) were
      performed to identify within-subject differences (test-retest, n=6), and operator
      and trial differences (intra- and inter-operator, n=20) for the MUP morphological
      variables. The within-subject reliability, as well as the intra- and inter
      operator reliability were estimated using intraclass correlation coefficients
      (ICCs). The 95% limits of agreement were calculated to measure within-subject and
      between operator agreements. MUP durations were found to be significantly
      different between days (p<0.05). For intra- and inter-operator reliability, a
      significant difference was found within and between the operators for MUP
      duration, and between the operators for MUP number of turns (p<0.05). SMUP
      morphological parameters yielded higher ICC values for both intra (0.96-0.99) and
      inter (0.96-0.99) operator scores when compared to MUP morphological parameters
      (intra-operator: 0.81-0.99; and inter-operator: 0.67-0.98). Mean motor unit (MU)
      firing rate was found to be a highly reliable measure for both intra- and inter
      operators (0.99-0.97, respectively). The between-operator agreement was above 95%
      for all morphological parameters. These results concerning within-subject, intra-
      and inter-operator reliability and levels of agreement for quantitative motor
      unit analysis suggest that DQEMG provides sufficiently consistent results to
      allow it to be effectively used for QEMG analysis. Needle-detected MUP morphology
      although clinically useful in the diagnosis and monitoring of neuropathies, was
      not as reliable as surface MUP QEMG measures.

PMID- 18053580
TI  - Light room therapy effective in mild forms of seasonal affective disorder--a
      randomised controlled study.
AB  - BACKGROUND: The most common way to provide bright light therapy to Swedish
      patients with Seasonal Affective Disorder (SAD), is treatment in a light therapy
      room. Since few studies have evaluated treatment provided in this setting and few
      have evaluated the effect of bright light in sub-clinical SAD (S-SAD), such a
      study including a one-month follow-up was designed. METHODS: Fifty adults
      recruited from a previous prevalence study and clinically assessed as having SAD
      or S-SAD, were randomised to treatment in a light room or to a three-week waiting
      list control group. The Hamilton Depression Rating Scale-Seasonal Affective
      Disorders Self-rating 29-items Version (SIGH-SAD/SR) was used to measure
      depressive mood at baseline, directly following treatment and at the one-month
      follow-up. RESULTS: ANCOVA with adjustment for baseline depression score, showed
      a significant main effect for the light room therapy group (p<0.001). Fifty-four
      percent (n=13/24) improved > or = 50% while no such improvement was seen in the
      control condition (n=0/24). After merging the two groups, repeated measures ANOVA
      confirmed the experimental analysis (p<0.001). At the one-month follow-up, 83.0%
      (n=39/47) had improved > or = 50% and 63.8% (n=30/47) had normal depression
      scores, i.e. < or = 8. CONCLUSIONS: Light room therapy was effective in reducing
      depressive symptoms in subjects with winter depressive mood. Results were
      maintained over a period of one month.

PMID- 18053581
TI  - Quantifying links between acute myocardial infarction and depression, anxiety and
      schizophrenia using case register databases.
AB  - AIMS: To quantify the association between depression and acute myocardial
      infarction (AMI) in a large sample using case registers, and examine whether any
      such link is specific to depression or might more reflect mental illness status
      in general. METHODS AND RESULTS: Accessing the Danish Psychiatric Central
      Research Register (PCR), patients with a diagnosis of depression were extracted
      and followed for up to 24 years for episodes of AMI. We used mentally healthy age
      and sex-matched controls, and as comparator diagnostic groups, we studied
      patients with anxiety and schizophrenia. A positive association between
      depression and AMI was found with an incidence rate ratio (IRR) of 1.16 (CI: 1.10
      1.22). The association was not unique for the depressed individuals, but was also
      found for anxiety patients, where it was even stronger (IRR=1.56, CI: 1.35-1.79)
      than for the depressed patients. A negative association (IRR=0.77, CI: 0.65-0.91)
      was quantified for schizophrenia, arguing against any link with AMI being
      determined by psychiatric disorder status per se. LIMITATIONS: Being a register
      study, not all potential confounding variables could be examined. CONCLUSION:
      Findings quantify significant associations between depression and AMI as well as
      between anxiety and AMI, and argue that these two psychiatric disorders should be
      added to the list of risk factors to coronary artery disease.

PMID- 18053582
TI  - Functional analysis of CD8+ T cell responses to the onconeural self protein cdr2
      in patients with paraneoplastic cerebellar degeneration.
AB  - Paraneoplastic cerebellar degeneration (PCD) is linked to an immune response
      against cerebellar degeneration related antigen 2 (cdr2) co-expressed in tumor
      and Purkinje neurons. Here, comprehensive immune-assessment assays were used to
      analyze CD8(+) T cells from 7 PCD patients, but no evidence was found of CD8(+) T
      cells specific for either of two previously described cdr2 epitopes (cdr2-1 and
      cdr2-2). In contrast, viral-specific CD8(+) T cells from healthy volunteers and
      PCD patients were measurable. These findings are inconsistent with an obligate
      role for cdr2-1- or cdr2-2-specific CD8(+) T cells in the pathogenesis of PCD.

PMID- 18053583
TI  - Hearing loss in pediatric patients with isolated nonsyndromic sagittal
      synostosis.
AB  - OBJECTIVE: Recent studies have shown increased rates of speech, language,
      cognitive and behavioral abnormalities in patients with isolated nonsyndromic
      sagittal synostosis. Little is known regarding the prevalence and type of hearing
      abnormalities in children with craniosynotosis. This study characterizes hearing
      loss in pediatric patients with isolated nonsyndromic sagittal synostosis.
      METHODS: Retrospective chart review of isolated nonsyndromic sagittal synostosis
      patients in a pediatric craniofacial clinic to determine the prevalence,
      severity, and type of hearing loss. RESULTS: Fifteen of 57 patients with isolated
      nonsyndromic sagittal synostosis had hearing loss (26% with a 95% confidence
      interval of 14.9 to 37.7%). Twelve patients demonstrated a conductive loss and
      three an unspecified type of loss (no bone conduction thresholds were recorded
      for these patients). The prevalence of conductive hearing loss in our population
      was 21% with a 95% confidence interval of 10.4 to 31.6%. All cases of hearing
      loss were mild or moderate in severity. CONCLUSIONS: The most common hearing
      impairment in patients with isolated nonsyndromic sagittal synostosis is
      conductive hearing loss likely secondary to middle ear effusion. These patients
      do not appear to have a higher frequency of middle ear effusion and conductive
      hearing loss than the normal population of comparable age. We conclude that there
      is no evidence of increased risk of hearing loss in our study population. We
      infer that hearing loss does not play a causative role in the elevation of risk
      for speech, language, behavioral and cognitive impairments which these patients
      experience. Health care professionals are obligated to ensure that conductive
      loss from middle ear effusion does not exacerbate these impairments. This
      obligation can safely be performed by managing hearing loss in the INSS
      population similar to hearing loss in comparably aged normal children.

PMID- 18053584
TI  - Auditory brainstem responses as a clinical evaluation tool in children after
      perinatal encephalopathy.
AB  - Auditory brainstem responses (ABR) reveals the neurophysiological status of the
      neural axis. In this study we compared the ABR of healthy children, under 1-year
      old, with children who suffered from perinatal encephalopathy (PE). OBJECTIVE:
      The purpose of this study was to characterize the ABR differences between
      children with PE and healthy children in order to identify groups with specific
      neurophysiological profiles, associated with their neurological condition.
      METHODS: Thirty-six children with perinatal encephalopathy (PE) and 36 healthy
      children, ages 1-12 months, were studied. The variables considered were:
      latencies of waves I, II, N1, III, V, and N2; interpeak latency interval (IPL) of
      waves I-III, III-V, and I-V; as well as amplitudes of waves I, III, and V. The
      results were analyzed using ANOVA, as well as Ji(2), and Ward's cluster analysis.
      RESULTS: The absolute latencies of the ABR showed an inverse correlation with the
      children's age. Latencies of waves I, II, N1, V, and N2, IPL III-V, and amplitude
      of waves III and V show significant differences (p<0.05) between healthy and PE
      children. Children with PE showed greater absolute latencies and larger wave
      amplitudes than the control group. Ward's cluster analysis, used to define the
      groups with similar functional characteristics, revealed three groups: fast,
      intermediate, and slow-responders, depending on their wave latencies and IPL wave
      amplitudes. These groups were gender- (p<0.03), age- (p<0.0001), and neurological
      damage- (p<0.01) related. CONCLUSIONS: Our data clearly show that the ABR
      obtained from PE children differ from ABR obtained from healthy children. PE
      infants showed larger wave latencies, intervals amplitudes than the control
      group. Three functional profiles resulted from the groups established using the
      Ward's method, and these indicate their neurological functional condition.

PMID- 18053585
TI  - Automated extraction and quantitation of oncogenic HPV genotypes from cervical
      samples by a real-time PCR-based system.
AB  - Accurate laboratory assays for the diagnosis of persistent oncogenic HPV
      infection are being recognized increasingly as essential for clinical management
      of women with cervical precancerous lesions. HPV viral load has been suggested to
      be a surrogate marker of persistent infection. Four independent real-time
      quantitative TaqMan PCR assays were developed for: HPV-16, -31, -18 and/or -45
      and -33 and/or -52, -58, -67. The assays had a wide dynamic range of detection
      and a high degree of accuracy, repeatability and reproducibility. In order to
      minimize material and hands-on time, automated nucleic acid extraction was
      performed using a 96-well plate format integrated into a robotic liquid handler
      workstation. The performance of the TaqMan assays for HPV identification was
      assessed by comparing results with those obtained by means of PCR using consensus
      primers (GP5+/GP6+) and sequencing (296 samples) and INNO-LiPA analysis (31
      samples). Good agreement was found generally between results obtained by real
      time PCR assays and GP(+)-PCR system (kappa statistic=0.91). In conclusion, this
      study describes four newly developed real-time PCR assays that provide a reliable
      and high-throughput method for detection of not only HPV DNA but also HPV
      activity of the most common oncogenic HPV types in cervical specimens.

PMID- 18053586
TI  - Towards a better resolution of hepatitis C virus variants: CLIP sequencing of an
      HCV core fragment and automated assignment of genotypes and subtypes.
AB  - Commercially available assays for typing of hepatitis C virus (HCV) isolates
      satisfy the current clinical needs. They are, however, limited in their ability
      to identify the multitude of existing HCV subtypes correctly. Therefore, these
      kits should only be used cautiously in epidemiological studies and will also not
      meet future clinical demands which might arise, e.g., from the application of HCV
      subtype-specific antiviral compounds. In an attempt to overcome the drawbacks of
      commercial typing procedures based on the analysis of the 5' untranslated region
      (5' UTR), an approach was developed which relies on CLIP sequencing of an HCV
      core fragment with automated assignments of types and subtypes via an originally
      created "core-specific" sequence database. The performance characteristics of the
      new technique were evaluated in comparison to the Trugene 5' NC Genotyping Kit.
      The core-based sequencing method could regularly detect HCV isolates of genotypes
      1-6 with an analytical sensitivity of 5000 IU/ml. The accuracy of typing results
      obtained by the Trugene test was 97% (genotypes) and 81% (subtypes). The core
      linked approach classified all HCV strains correctly on the level of genotypes
      and led to an adequate subtype assignment in 96% of all cases. This analytical
      performance characteristics recorded for the newly devised typing technique was
      superior to those reported for all commercially available assays, including a
      most recently released new generation of the line probe assay. Consequently, CLIP
      sequencing of an HCV core fragment with subsequent automated assignment of types
      and subtypes can be confidently used in clinical laboratory practice to answer
      current and also future questions in the context of HCV typing.

PMID- 18053587
TI  - Progressive encephalomyelitis with rigidity and myoclonus in an 81-year-old
      patient.
AB  - We present the case of an 81-year-old female with severe rigidity, stiffness and
      superimposed muscle spasms that represents the oldest reported patient with
      progressive encephalomyelitis with rigidity and myoclonus. Two associated
      autoimmune disorders (diabetes mellitus and Hashimoto's thyoiditis) were recently
      diagnosed. A paraneoplastic origin was excluded. The spectrum of differential
      diagnoses including classic Stiff-Person syndrome and paraneoplastic Stiff-Person
      syndrome is discussed.

PMID- 18053588
TI  - Anti-tumor necrotic factor antibody for treatment of neuro-Behcet's disease, a
      case report.

PMID- 18053589
TI  - Does antiviral therapy have a role in the control of Japanese encephalitis?
AB  - Approximately 2 billion people live in countries where Japanese encephalitis (JE)
      presents a significant risk to humans and animals, particularly in China and
      India, with at least 700 million potentially susceptible children. The combined
      effects of climate change, altered bird migratory patterns, increasing movement
      of humans, animals and goods, increasing deforestation and development of
      irrigation projects will inevitably lead to further geographic dispersal of the
      virus and an enhanced threat. Although most human infections are mild or
      asymptomatic, some 50% of patients who develop encephalitis suffer permanent
      neurologic defects, and 25% die. Vaccines have reduced the incidence of JE in
      some countries. No specific antiviral therapy is currently available. Interferon
      alpha-2a was tested in a double-blind placebo-controlled trial on children with
      Japanese encephalitis, but with negative results. There is thus a real need for
      antivirals that can reduce the toll of death and neurological sequelae resulting
      from infection with JE virus. Here we briefly review the epidemiological problems
      presented by this virus, the present state of drug development and the
      contributory role that antiviral therapy might play in developing future control
      strategies for JE.

PMID- 18053590
TI  - Antisense RNA and RNAi in protozoan parasites: working hard or hardly working?
AB  - The complex life cycles of many protozoan parasites require the ability to
      respond to environmental and developmental cues through regulated gene
      expression. Traditionally, parasitologists have investigated these mechanisms by
      identifying and characterizing proteins that are necessary for the regulated
      expression of the genetic material. Although often successful, it is clear that
      protein-mediated gene regulation is only part of a complex story in which RNA
      itself is endowed with regulatory functions. Herein, we review both the known and
      potential regulatory roles of two types of RNA pathways within protozoan
      parasites: the RNA interference pathway and natural antisense transcripts. A
      better understanding of the native role of these pathways will not only enhance
      our understanding of the biology of these organisms but also aid in the
      development of more robust tools for reverse genetic analysis in this post
      genomic era.

PMID- 18053591
TI  - Referencing for reviews: How to distinguish unwillingness from mission
      impossible.
AB  - Selecting the most relevant literature for a state-of-the-art review article may
      result in the unintentional exclusion of valuable contributions, despite the most
      genuine intention of comprehensiveness. Some of these omissions, however, can be
      sensibly justified by a number of factors, such as language barriers, lack of
      abstract and/or online full-text article, type of manuscript and date of
      publication, whose concurrence makes simply unfeasible the gathering of the most
      basic information, indispensable for the citation. In this case, even the oceanic
      collection of scientific contributions contained in the database Medline may
      become underpowered.

PMID- 18053592
TI  - Effects of carvedilol on right ventricular ejection fraction and cytokines levels
      in patients with systolic heart failure.
AB  - BACKGROUND: Right ventricular (RV) dysfunction frequently complicates advanced
      left ventricular (LV) heart failure and contributes to an unfavorable prognosis.
      It is known that carvedilol increases left ventricular ejection fraction (LVEF)
      significantly, and carvedilol reduces mortality by associating with improvement
      in LV function. However, the effect of carvedilol on RV function in heart failure
      has not adequately been studied, so far. The objective is to establish whether
      the addition of carvedilol has an additive beneficial effect on RVEF and
      cytokines levels in patients with heart failure who are already receiving
      treatment with angiotensin-converting enzyme (ACE) inhibitors, digoxin and
      diuretics. METHODS: In this single-centre, prospective, randomized study, 74
      patients with heart failure with an LVEF less than 40% and already receiving
      digoxin, ACE inhibitors and diuretics for 6 months as the standard therapy were
      randomly assigned to receive either carvedilol (n=44) or placebo (n=30). Patients
      received an initial dosage of 6.25 mg carvedilol or placebo twice daily for 2
      weeks, which was then increased at 2-week intervals (if tolerated), first to 12.5
      mg and, finally, to a target dosage of 25 mg twice daily. Clinical examinations,
      radionuclide studies, and determinations of plasma levels of tumour necrosis
      factor-alpha (TNF-alpha), interleukin (IL)-2 and IL-6 were performed at baseline
      and repeated 4 months after random assignment. Primary end points were New York
      Heart Association functional class, RVEF and plasma cytokines levels. RESULTS:
      Patients treated with carvedilol had a significant improvement in functional
      class compared with the baseline values (P=0.001), with a decrease in the levels
      of cytokines (IL-6 [P=0.02] and TNF-alpha [P=0.02]). LVEF increased from 21.4+/
      8.8% to 27.8+/-10.8% and RVEF increased from 28.8+/-4.2% to 36.3+/-2.6% in the
      carvedilol group (P=0.003). CONCLUSIONS: Carvedilol treatment for 4 months
      resulted in a significant improvement of RVEF, which paralleled the improvement
      of LVEF and the decreasing of TNF-alpha and IL-6 levels in patients with systolic
      HF.

PMID- 18053593
TI  - Exceptional survival: acute coronary syndrome in a 56-year-old patient with
      Takayasu's arteritis.

PMID- 18053594
TI  - Candesartan improves myocardial damage in obese mice with viral myocarditis and
      induces cardiac adiponectin.
AB  - PURPOSE: To clarify the mechanism of the effects of angiotensin II receptor type
      1 antagonist, candesartan, upon cardiac adiponectin in the combination of
      myocarditis with obesity, we examined obese KKAy mice with acute viral
      myocarditis treated by candesartan and investigated cardiac adiponectin
      regulation. METHODS: Mice were divided into candesartan early treatment group
      (Can-early) receiving orally candesartan at daily dose of 10 mg/kg 7 days
      starting before viral inoculation and then 7 days; candesartan late treatment
      group (Can-late) or vehicle (Vehicle) receiving candesartan starting
      simultaneously with viral inoculation and then 7 days. Encephalomyocarditis virus
      was used to induce the acute viral myocarditis. Differences in myocardial
      damages, serum adiponectin and myocardial expression of adiponectin, tumor
      necrosis factor-alpha (TNF-alpha), CCAAT/enhancer binding proteinalpha
      (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPAR-gamma)
      and nuclear factor-kappaB (NF-kappaB) mRNA among three groups were determined on
      days 0, 4 and 7 after viral inoculation. RESULTS: Mice in Can-early and Can-late
      groups showed reduced myocardial necrosis and cellular infiltration as compared
      with those in the Vehicle. On day 4 the circulating adiponectin levels were
      significantly higher in Can-early than those in Vehicle. Mice in Vehicle had
      significantly reduced in myocardial adiponectin mRNA after viral myocarditis.
      Cardiac adiponectin mRNA was significantly higher in Can-early and in Can-late
      than in Vehicle on days 4 and 7. Cardiac C/EBPalpha in Can-early and Can-early
      groups was significantly increased on day 4. Myocardial NF-kappaB and TNF-alpha
      mRNA in Can-early and Can-late groups were significantly reduced on day 7.
      CONCLUSION: Candesartan treatment improved myocardial injury in obese mice with
      acute viral myocarditis and induced expression of cardiac adiponectin with the
      induction of C/EBPalpha as well as the reduction of cardiac NF-kappaB and TNF
      alpha.

PMID- 18053595
TI  - Cardiac remodeling and predictors for cardiac death in long-term follow-up of
      subjects with chronic Chagas' heart disease: a mathematical model for progression
      of myocardial damage.
AB  - In a prospective longitudinal study the occurrence of cardiac death was
      investigated and ongoing cardiac remodeling retrospectively analyzed in regard to
      adverse outcome. A cohort of 50 subjects with chronic Chagas' disease stratified
      according to Los Andes groups 1, 2 and 3 were followed-up for (mean+/-SD) 84.2+/
      39.0 months. Follow-up was abbreviated by ventricular tachycardia ([VT]
      incidence: 3.0+/-7.0% year(-1)), first atrial fibrillation episode lasting >24 h
      ([AF] incidence: 3.3+/-1.0% year(-1)), nonfatal embolic stroke (incidence: 1.3+/
      1.0% year(-1)), and cardiac death (mortality rate: 2.3+/-0.8% year(-1)). The
      relative risk of Los Andes group 3, VT, AF and stroke for cardiac death was,
      respectively, 25.3 (95%CI [3.5-182.6]), 3.0 (95%CI [1.2-7.3]), 3.6 (95%CI [1.2
      10.9]) and 1.1 (95%CI [0.2-7.2]). In a multivariate Cox proportional-hazard
      model, Los Andes group 3 (hazard ratio=24.5; 95%CI [3.2-189.2]; p<0.01) was
      independent predictor for cardiac death. LAD and LV mass and not LVEF variation
      rates differed among group 1 (respectively, 0.03+/-0.1 cm year(-1); 2.4+/-5.7 g
      year(-1) and -0.1+/-2.4% year(-1)), group 2 (0.04+/-0.1 cm year(-1); 3.7+/-8.8 g
      year(-1) and -0.8+/-1.4% year(-1)) and group 3 (0.13+/-0.1 cm year(-1), p<0.001;
      21.7+/-10.1 g year(-1), p<0.001 and -1.4+/-2.5% year(-1), p=0.26). Variables on
      admission were linearly related to respectively variation rates (r=0.71; p=0.02)
      composing a first order linear process with 0.07 months(-1) time constant. In
      chronic Chagas' disease, initial clinical status is an independent predictor for
      cardiac death and determines the progression rate of myocardial damage.

PMID- 18053597
TI  - Multimodality cardiac imaging for the noninvasive characterization of
      intracardiac neoplasms.

PMID- 18053598
TI  - CT angiography images of an anomalous right coronary artery.
AB  - We describe a 33-year-old male with angina pectoris who was found to have
      abnormal origin and course of right coronary artery from left aortic cusp. The
      abnormal origin was identified by conventional coronary angiography but the
      abnormal course of the vessel between ascending aorta and the main pulmonary
      artery was precisely delineated by high resolution CT angiography. Patient
      underwent successful surgical transposition of the anomalous vessel with complete
      resolution of symptoms.

PMID- 18053599
TI  - Hypertrophic cardiomyopathy is a global disease including China.

PMID- 18053600
TI  - Retrograde percutaneous recanalization of coronary chronic total occlusions:
      outcomes from 17 patients.
AB  - Given their suboptimal success rates, coronary chronic total occlusions (CTO)
      represent one of the last challenges of percutaneous coronary intervention (PCI).
      Among several novel techniques, the retrograde approach is one of the most
      promising, but it is still incompletely described. We report our 5-year
      experience in retrograde PCI for CTOs. We abstracted patient and procedural data
      on all cases with attempted retrograde approach. End-points were technical and
      procedural success, plus long-term major adverse cardiovascular events (MACE).
      The retrograde approach was used in 17 patients, with procedural success in 12
      (71%), including 9 CTOs of right coronary, 2 of left circumflex, and 2 of left
      main arteries. Conversely, 4 cases of technical failure and 1 post-procedural
      myocardial infarction in an otherwise angiographically successful procedure were
      found. Causes of retrograde failure were: inability to deliver the balloon
      through the chosen collateral in 2 cases, inability to retrogradely cross the
      distal stump with the wire in 1 case, and interruption of the procedure due to
      rupture of a minor septal collateral branch during attempts at advancing the non
      inflated balloon in 1 case. In all patients with retrograde failure, subsequent
      antegrade attempts could be carried out, with ultimate success in everybody.
      Follow-up at 24+/-21 months showed an overall MACE rate of 23%. In conclusion,
      the retrograde approach appears feasible and safe, and its application can be
      envisioned as a promising alternative strategy in selected patients in whom
      antegrade approaches fail or are deemed unsafe.

PMID- 18053601
TI  - Selective isolation of bacterial DNA from human clinical specimens.
AB  - We evaluated two DNA preparation strategies (MolYsis, Molzym GmbH & Co. KG,
      Bremen, Germany) and Pureprove, SIRS-Lab GmbH, Jena, Germany) to selectively
      extract bacterial DNA from human clinical samples. By testing 16 oral samples we
      found that human DNA could be largely eliminated while detectable levels of
      bacterial DNA were obtained with all samples. Both approaches hold great
      potential for microbial diagnostic systems.

PMID- 18053602
TI  - Pulmonary injury and tumor response after stereotactic body radiotherapy (SBRT):
      results of a serial follow-up CT study.
AB  - PURPOSE: To evaluate the CT morphological pattern of tumor response and pulmonary
      injury after stereotactic body radiotherapy (SBRT) for early stage non-small lung
      cancer (NSCLC) and pulmonary metastases. MATERIALS AND METHODS: Seventy patients
      (lesions n=86) with pulmonary metastases (n=48) or primary early stage NSCLC
      (n=38) were analyzed. Patients were treated with hypofractionated SBRT (three to
      eight fractions with a single dose between 6 and 12.5 Gy; n=56) or with
      radiosurgery (26 Gy; n=30). The pattern and sequence of pulmonary injury and of
      tumor response was evaluated in 346 follow-up CT studies, 4.9 on average.
      RESULTS: Symptomatic pneumonitis was observed in 10% after a median interval of 5
      months. No pulmonary reaction was observed in most patients 6 weeks after
      treatment; spotted-streaky condensations were characteristic between 3 months and
      6 months. Dense consolidation and retraction started after 9 months and the
      fibrotic remodelling process continued for years. Ten targets relapsed after a
      median of 7 months. At 12 months complete response was seen in 43% and the
      differentiation of residual tumor from pulmonary reaction was not possible in
      33%. CONCLUSIONS: A typical sequence of pulmonary reactions was observed without
      differences between hypofractionated treatment and radiosurgery. Onset of
      pneumonitis was later compared to conventionally fractionated radiotherapy.

PMID- 18053603
TI  - Test-retest reliability of P50, N100 and P200 auditory sensory gating in healthy
      subjects.
AB  - RATIONALE: Suppression of middle latency auditory evoked responses is considered
      an index for the multistage sensory gating process. This has been observed in
      sequentially occurring P50, N100 and P200 components in a dual-click procedure.
      Since P50 sensory gating deficits have been observed in schizophrenic patients
      and first degree relatives, this parameter was suggested as an intermediate
      phenotype of the disease. However, most studies only show a low reliability for
      P50 sensory gating and neither N100 nor P200 sensory gating have been
      sufficiently tested. METHODS: Reliability of P50, N100 and P200 sensory gating
      was measured in 41 healthy subjects in two sessions, four weeks apart, using
      intra-class correlation. Sensory gating was calculated as ratio-gating (second
      response magnitude/first response magnitude x100) as well as difference-gating
      (first response magnitude minus second response magnitude). RESULTS: The
      difference-gating showed good to excellent reliabilities independently of the
      amplitude-measurement method applied (P50 peak-to-peak 0.75 and baseline-to-peak
      0.74, N100 peak-to-peak 0.63 and baseline-to-peak 0.70, P200 peak-to-peak 0.82
      and baseline-to-peak 0.79). Regarding ratio-gating, best temporal stability was
      observed for the P200 (peak-to-peak 0.58 and baseline-to-peak 0.62). Reliability
      of P50 ratio-gating strongly depends on the amplitude-measurement method (peak-to
      peak 0.0 and baseline-to-peak 0.46). CONCLUSION: Regarding long-term reliability
      in healthy subjects the difference-gating of all three evoked responses and the
      ratio-gating of the P200 component may be useful tools for clinical or
      intermediate phenotype studies measuring different stages of the auditory sensory
      gating process. In contrast, the reliability of the P50 and N100 ratio-gating
      component seems to be insufficient for this purpose. However, long-term
      reliability remains to be confirmed in clinical samples.

PMID- 18053604
TI  - Possible involvement of neurons in locus coeruleus in inhibitory effect on
      glossopharyngeal expiratory activity in a neonatal rat brainstem-spinal cord
      preparation in vitro.
AB  - In this study, we found that a certain motor branch of glossopharyngeal (IX)
      motor nerves stably exhibits not only inspiratory activity but also expiratory
      activity with pons removal in neonatal rat brainstem-spinal cord preparations in
      vitro. Because this finding indicates that IX expiratory activity is masked by an
      inhibitory mechanism operating in the pons, we sought to determine the candidate
      neurons that exert an inhibitory effect on IX expiratory activity. IX expiratory
      activity was observed when only the pons was perfused with noradrenaline (NA) or
      clonidine (alpha2 adrenergic receptor agonist), but not when NA and yohimbine
      (alpha2 adrenergic receptor antagonist) were perfused together. IX expiratory
      activity was also observed following the removal of the dorsal pons but not the
      ventral pons. The local administration of clonidine into the bilateral locus
      coeruleus (LC) evoked burst discharges during the expiratory phase in the IX
      motor rootlet. These results suggest that neurons in the LC that possess an
      alpha2 adrenergic receptor on the membrane surface exert a tonic inhibitory
      effect on IX expiratory activity in neonatal rat brainstem-spinal cord
      preparations.

PMID- 18053605
TI  - Acute non-cytopathic bovine viral diarrhea virus infection induces pronounced
      type I interferon response in pregnant cows and fetuses.
AB  - Bovine viral diarrhea virus (BVDV) infection occurs in the cattle population
      worldwide. Non-cytopathic (ncp) BVDV strains cause transient infection (TI) or
      persistent infection (PI) depending on the host's immune status. Immunocompetent
      adult animals and fetuses in late gestation resolve the infection. Fetal
      infection in early gestation results in PI with chronic viremia and life-long
      viral shedding, ensuring virus perpetuation in the population. Eighteen pregnant
      heifers, divided into three groups, were intranasally inoculated with ncp BVDV2
      virus early (day 75) and late (day 175) in gestation, or kept BVDV-naive. Fetuses
      were retrieved on day 190. Antiviral activity in blood of dams and fetuses,
      maternal expression of interferon (IFN) stimulated gene 15kDa (ISG15),
      virological and serological status of heifers and fetuses, and fetal growth were
      studied. A pronounced antiviral activity in blood of heifers and TI fetuses
      during acute BVDV infection was accompanied by drastic up-regulation of ISG15
      mRNA in maternal blood. Only one PI fetus expressed low IFN response 115 days
      post inoculation despite high BVDV antigen and RNA levels. PI fetuses presented
      with growth retardation. Infection of pregnant heifers with ncp BVDV2 early in
      gestation adversely affects fetal development and antiviral responses, despite
      protective immune responses in the dam.

PMID- 18053606
TI  - Characterization of the intracellular dynamics of a non-degradative pathway
      accessed by polymer nanoparticles.
AB  - Recently, 24 nm polymer nanoparticles were found to access a privileged non
      degradative intracellular pathway that leads to perinuclear accumulation. Here,
      we report the intracellular dynamics of vesicles containing polymer nanoparticles
      within this non-degradative pathway, characterized by clathrin- and caveolae
      independent endocytosis, as compared to endosomes originating from classical
      clathrin-mediated endocytosis. Similar to transport of acidic endosomes and
      lysosomes, the dynamic movements of non-degradative vesicles exhibit substantial
      heterogeneity, including caged diffusion and pearls-on-a-string trajectories, a
      reflection of microtubule-dependent active transport that leads to rapid
      accumulation near the cell nucleus. However, the ensemble-averaged intracellular
      transport rate of vesicles in the non-degradative pathway is 4-fold slower than
      that of the acidic vesicles of late endosomes and lysosomes, highlighted by a 3
      fold smaller fraction of actively transported vesicles. The distinct
      intracellular dynamics further confirms that small nanoparticles are capable of
      entering cells via a distinct privileged pathway that does not lead to lysosomal
      processing. This non-degradative pathway may prove beneficial for the delivery of
      therapeutics and nucleic acids to the nucleus or nearby organelles.

PMID- 18053607
TI  - Nanoimprint lithography based fabrication of shape-specific, enzymatically
      triggered smart nanoparticles.
AB  - Our ability to precisely manipulate size, shape and composition of nanoscale
      carriers is essential for controlling their in-vivo transport, bio-distribution
      and drug release mechanism. Shape-specific, "smart" nanoparticles that deliver
      drugs or imaging agents to target tissues primarily in response to disease
      specific or physiological signals could significantly improve therapeutic care of
      complex diseases. Current methods in nanoparticle synthesis do not allow such
      simultaneous control over particle size, shape and environmentally-triggered drug
      release, especially at the sub 100 nm range. We report here a high-throughput
      nanofabrication technique using synthetic and biological macromers (peptides) to
      produce highly monodisperse, enzymatically-triggered nanoparticles of precise
      sizes and shapes. Particles as small as 50 nm were fabricated on silicon wafers
      and harvested directly into aqueous buffers using a biocompatible, one-step
      release technique. We further demonstrate successful encapsulation and precisely
      controlled enzyme-triggered release of antibodies and nucleic acids from these
      nanoparticles, thus providing a potential means for disease-controlled delivery
      of biomolecules.

PMID- 18053608
TI  - Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative
      diabetic retinopathy.
AB  - PURPOSE: We studied the roles of vascular endothelial growth factor (VEGF), its
      receptor (flt-1), advanced glycation end products (AGEs), and macrophages in the
      development of proliferative diabetic retinopathy. METHODS: Ocular fluid and
      small specimens of iris and neovascular membrane were obtained from 30 patients
      who underwent vitreous surgery (19 eyes with proliferative diabetic retinopathy
      [PDR], 11 eyes with non-diabetic ocular diseases). VEGF and AGE levels in ocular
      fluid were assayed by ELISA. Immunohistochemical studies of VEGF, flt-1, AGEs,
      and macrophage were performed on the ocular tissues. RESULTS: The mean VEGF and
      AGE levels in the vitreous (695.7pg/ml and 2.4mg/ml, respectively) were
      significantly higher in diabetic than in non-diabetic eyes (25.9pg/ml, p=0.0007
      and 1.3mg/ml, p=0.005, respectively). Likewise, in the aqueous humor, VEGF and
      AGE levels were significantly higher in diabetic than in non-diabetic eyes. VEGF
      levels in the vitreous and aqueous humor were correlated significantly (r=0.6;
      p=0.02), but AGEs were not. The VEGF levels were not correlated with AGE levels
      in the aqueous or vitreous. In the iris, VEGF, AGEs, and macrophages were stained
      more prominently in the specimens from patients with diabetes than from patients
      without diabetes, while flt-1 staining did not differ. The Neovascular membranes
      were stained much more prominently for all (VEGF, flt-1, AGEs and macrophages)
      even when compared with the iris from patients with diabetes. CONCLUSIONS: By
      analyzing aqueous and vitreous humor, proliferative membranes, and iris from the
      same patients, the current clinical study strongly supports previous reports that
      showed the role of VEGF, macrophages, and AGEs in the development of diabetic
      proliferative retinopathy. From the results of the current study, we showed that
      flt-1 plays an important role in the development of retinal neovascular membranes
      but the role is uncertain in the iris and retina.

PMID- 18053609
TI  - Health systems' responses to 25 years of HIV in Europe: inequities persist and
      challenges remain.
AB  - Europe is currently experiencing the fastest rate of growth of HIV of any region
      of the world. An analysis of policy and health system responses to the HIV
      epidemic in Europe and central Asia (hereafter referred to as Europe) over the
      last 25 years reveals considerable heterogeneity. In general, while noting
      hazards of broad generalisations and the differences that exist across countries
      in a particular grouping, effective policies to control HIV have been implemented
      more widely in western than in central and eastern Europe. However, the evidence
      suggests persistence of inequalities in access to preventive and treatment
      services, with those at highest risk, such as commercial sex workers, prisoners,
      intravenous drug users, and migrants often particularly disadvantaged, despite
      many targeted programmes. Responses in individual countries, especially in the
      early stages of the epidemic, were influenced by specific cultural and political
      factors. Strong leadership and active involvement by civil society organisations
      emerge as important factors for success but also a limiting factor to the
      response observed in eastern Europe, where civil society or NGO culture is weak
      as compared to western Europe. Scaling up of effective responses in many
      countries in eastern Europe will be challenging-where increased financial
      resources will have to be accompanied by broader changes to health system
      organization with greater involvement of the civil society in planning and
      delivery of client-focused services.

PMID- 18053610
TI  - Improving brain tumor characterization on MRI by probabilistic neural networks
      and non-linear transformation of textural features.
AB  - The aim of the present study was to design, implement and evaluate a software
      system for discriminating between metastatic and primary brain tumors (gliomas
      and meningiomas) on MRI, employing textural features from routinely taken T1 post
      contrast images. The proposed classifier is a modified probabilistic neural
      network (PNN), incorporating a non-linear least squares features transformation
      (LSFT) into the PNN classifier. Thirty-six textural features were extracted from
      each one of 67 T1-weighted post-contrast MR images (21 metastases, 19 meningiomas
      and 27 gliomas). LSFT enhanced the performance of the PNN, achieving
      classification accuracies of 95.24% for discriminating between metastatic and
      primary tumors and 93.48% for distinguishing gliomas from meningiomas. To improve
      the generalization of the proposed classification system, the external cross
      validation method was also used, resulting in 71.43% and 81.25% accuracies in
      distinguishing metastatic from primary tumors and gliomas from meningiomas,
      respectively. LSFT improved PNN performance, increased class separability and
      resulted in dimensionality reduction.

PMID- 18053611
TI  - Enhancing drug absorption using lipids: a case study presenting the development
      and pharmacological evaluation of a novel lipid-based oral amphotericin B
      formulation for the treatment of systemic fungal infections.
AB  - The development of a safe and efficacious drug involves a balance between
      bioavailability, toxicity and disposition within the body. If the drug is
      hydrophobic or acid labile, oral administration may lead to poor systemic
      exposure, necessitating a parenteral treatment regime. Amphotericin B (AmpB) is
      one example of a well established, highly efficacious drug that has a 50 year
      history of intravenous therapy. AmpB formulated as a micellar dispersion
      (Fungizone; FZ) for IV use, remains one of the most effective agents in the
      treatment of systemic fungal infections, yet no oral formulations are currently
      commercially available. Recently, our laboratory has developed new oral lipid
      based AmpB formulations with enhanced gastrointestinal (GI) tract absorption and
      antifungal activity with minimum renal toxicity. This review article will discuss
      these findings and present data to support two potential mechanisms for the
      enhanced GI tract absorption of AmpB when formulated in this oral lipid-based
      delivery system, namely an increase in lymphatic drug transport and a decrease in
      pre-systemic transporter-mediated drug efflux.

PMID- 18053612
TI  - Tat peptide-mediated intracellular delivery of pharmaceutical nanocarriers.
AB  - Cell-penetrating peptides (CPPs) including TAT peptide (TATp) have been
      successfully used for intracellular delivery of a broad variety of cargoes
      including various nanoparticulate pharmaceutical carriers (liposomes, micelles,
      nanoparticles). Here, we will consider the main results in this area, with a
      special emphasis on TATp-mediated delivery of liposomes and DNA. We will also
      address the development of "smart" stimuli-sensitive nanocarriers, where cell
      penetrating function can be activated by the decreased pH only inside the
      biological target minimizing thus the interaction of drug-loaded nanocarriers
      with non-target cells.

PMID- 18053613
TI  - Induction of immune tolerance to facilitate beta cell regeneration in type 1
      diabetes.
AB  - A definitive cure for type 1 diabetes is currently being pursued with enormous
      effort by the scientific community. Different strategies are followed to restore
      physiologic production of insulin in diabetic patients. Restoration of self
      tolerance remains the milestone that must be reached in order to move a step
      further and recover a cell source capable of independent and functional insulin
      production. Multiple strategies aimed at modulation of both central and
      peripheral immunity must be considered. Promising results now show that the
      immune system can be modulated in a way that acquisition of a "diabetes
      suppressive" phenotype is possible. Once self-tolerance is achieved, reversal of
      the disease may be obtained by simply allowing physiologic rescue and/or
      regeneration of the beta cells to take place. Given that these outcomes have
      already been confirmed in humans, refinement of existing protocols along with
      novel methods adapted to T1DM reversal will allow translation into clinical
      trials.

PMID- 18053614
TI  - Protein and peptide transduction, twenty years later a happy birthday.
AB  - This commentary underscores the following aspects of Cell Permeable
      Peptides/Transduction Peptides (CPP/PTD) research. First the discovery of CPP/PTD
      takes its origin in the observation that some full-length transcription factors
      navigate between cells. The latter physiological origin is of interest as the
      significance of this new mode of signal transduction is not yet fully understood.
      A second point is that most breakthroughs in the domain have been made possible
      by long lasting collaborations between biologists, chemists and physicists. It is
      beyond doubt that the understanding of the mechanisms of secretion and
      internalization, in parallel with the development of new transduction compounds,
      not only peptides, will require that such collaborative efforts be amplified.
      Finally, although the domain is flourishing and our minds full of hope, it must
      be said that many points need to be resolved before getting close to bedside.
      Among these points are bio-disponibility, toxicity and specific addressing to
      body regions, cell types and intracellular compartments. In brief, beyond this
      happy birthday, there is still plenty of home work!

PMID- 18053616
TI  - Olanzapine blocks the sympathetic and hyperthermic reactions due to cerebral
      injection of orexin A.
AB  - Since experiments regarding a possible relation between olanzapine and orexin A
      has been scarcely reported in international literature, this experiment tested
      the effect of olanzapine on the sympathetic and thermogenic effects induced by
      orexin A. The firing rates of the sympathetic nerves to interscapular brown
      adipose tissue (IBAT), along with IBAT, colonic temperatures and heart rate were
      monitored in urethane-anesthetized male Sprague-Dawley rats before an injection
      of orexin A (1.5 nmol) into the lateral cerebral ventricle and over a period of
      150 min after the injection. The same variables were monitored in rats with an
      intraperitoneal administration of olanzapine (10mg/kg bw), injected 30 min before
      the orexin administration. The results show that orexin A increases the
      sympathetic firing rate, IBAT, colonic temperatures and heart rate. This increase
      is blocked by the injection of olanzapine. These findings indicate that
      olanzapine affects the complex reactions related to activation of orexinergic
      system.

PMID- 18053617
TI  - Neurodegeneration and peroxidases.
AB  - Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral
      sclerosis (ALS) are neurodegenerative diseases that affect different parts of the
      central nervous system. However, a review of the literature indicates that
      certain biochemical reactions involved in neurodegeneration in these three
      diseases are quite similar and could be partly identical. This article critically
      examines the similarities and, based on data from our own and other laboratories,
      proposes a novel explanation for neurodegeneration in these three diseases. We
      identified about 20 commonalities that exist in the neurodegenerative process of
      each disease. We hypothesize that there are two enzyme-catalyzed pathways that
      operate in affected neurons: an oxidative pathway leading to destruction of
      various neuronal proteins and lipids, and an apoptotic pathway which the body
      normally uses to remove unwanted and dysfunctional cells. Data from many
      laboratories indicate that oxidative reactions are primarily responsible for
      neurodegeneration, whereas apoptosis may well be a secondary response to the
      presence of neurons that have already been severely damaged by oxidative
      reactions. Attempts to inhibit apoptosis for the purpose of attenuating
      progression of these diseases may therefore be only of marginal benefit. Specific
      oxidative reactions within affected neurons led us to propose that one or more
      heme peroxidases may be the catalyst(s) involved in oxidation of proteins and
      lipids. Support for this proposal is provided by the recent finding that amyloi
      beta peptide may act as a peroxidase in AD. Possible participation of the
      peroxidase activity of cytochrome c, herein designated as cytochrome c(px) to
      distinguish it from yeast cytochrome c peroxidase, is discussed. Of special
      interest is our recent finding that many compounds that cause attenuation of
      neurodegeneration are inhibitors of the peroxidase activity of cytochrome c.
      Several inhibitors were subsequently identified as suicide substrates. Such
      inhibitors could be ideally suited for targeted clinical approaches aimed at
      arresting progression of neurodegeneration. Finally, it is possible that
      immobilized yet still active peroxidase(s) may be present in protein aggregates
      in AD, PD, and ALS. This activity could be the catalyst for the slow, self
      perpetuating and irreversible degeneration of affected neurons that occurs over
      long periods of time in these neurodegenerative diseases.

PMID- 18053615
TI  - Central leptin insufficiency syndrome: an interactive etiology for obesity,
      metabolic and neural diseases and for designing new therapeutic interventions.
AB  - This review critically reappraises recent scientific evidence concerning central
      leptin insufficiency versus leptin resistance formulations to explain metabolic
      and neural disorders resulting from subnormal or defective leptin signaling in
      various sites in the brain. Research at various fronts to unravel the
      complexities of the neurobiology of leptin is surveyed to provide a comprehensive
      account of the neural and metabolic effects of environmentally imposed
      fluctuations in leptin availability at brain sites and the outcome of newer
      technology to restore leptin signaling in a site-specific manner. The cumulative
      new knowledge favors a unified central leptin insufficiency syndrome over the, in
      vogue, central resistance hypothesis to explain the global adverse impact of
      deficient leptin signaling in the brain. Furthermore, the leptin insufficiency
      syndrome delineates a novel role of leptin in the hypothalamus in restraining
      rhythmic pancreatic insulin secretion while concomitantly enhancing glucose
      metabolism and non-shivering thermogenic energy expenditure, sequelae that would
      otherwise promote fat accrual to store excess energy resulting from consumption
      of energy-enriched diets. A concerted effort should now focus on development of
      newer technologies for delivery of leptin or leptin mimetics to specifically
      target neural pathways for remediation of diverse ailments encompassing the
      central leptin insufficiency syndrome.

PMID- 18053618
TI  - Brain structure and function related to cognitive reserve variables in normal
      aging, mild cognitive impairment and Alzheimer's disease.
AB  - Cognitive reserve (CR) is the brain's capacity to cope with cerebral damage to
      minimize clinical manifestations. The 'passive model' considers head or brain
      measures as anatomical substrates of CR, whereas the 'active model' emphasizes
      the use of brain networks effectively. Sixteen healthy subjects, 12 amnestic mild
      cognitive impairment (MCI) and 16 cases with mild Alzheimer's disease (AD) were
      included to investigate the relationships between proxies of CR and cerebral
      measures considered in the 'passive' and 'active' models. CR proxies were
      inferred premorbid IQ (WAIS Vocabulary test), 'education-occupation', a
      questionnaire of intellectual and social activities and a composite CR measure.
      MRI-derived whole-brain volumes and brain activity by functional MRI during a
      visual encoding task were obtained. Among healthy elders, higher CR was related
      to larger brains and reduced activity during cognitive processing, suggesting
      more effective use of cerebral networks. In contrast, higher CR was associated
      with reduced brain volumes in MCI and AD and increased brain function in the
      latter, indicating more advanced neuropathology but that active compensatory
      mechanisms are still at work in higher CR patients. The right superior temporal
      gyrus (BA 22) and the left superior parietal lobe (BA 7) showed greatest
      significant differences in direction of slope with CR and activation between
      controls and AD cases. Finally, a regression analysis revealed that fMRI patterns
      were more closely related to CR proxies than brain volumes. Overall, inverse
      relationships for healthy and pathological aging groups emerged between brain
      structure and function and CR variables.

PMID- 18053619
TI  - A transgenic rat model of Alzheimer's disease with extracellular Abeta
      deposition.
AB  - Many transgenic mouse models of Alzheimer's disease (AD) that deposit amyloid
      (Abeta) have been produced, but development of an Abeta-depositing rat model has
      not been successful. Here, we describe a rat model with extracellular fibrillar
      Abeta deposition. Two lines of Sprague Dawley rats with transgenes expressing
      human amyloid precursor protein (APP) with the familial AD (FAD) mutations
      K670N/M671L and K670N/M671L/V717I were crossed. Abeta production in the double
      homozygous rats was sufficient for deposition by 17-18 months of age. The age of
      onset of Abeta deposition was reduced by crossing in a third rat line carrying a
      human presenilin-1 (PS-1) transgene with the FAD M146V mutation. The triple
      homozygous line had an onset of Abeta deposition by 7 months of age. Deposits
      appeared similar to those observed in the mouse models and displayed surrounding
      glial and phosphorylated tau reactivity. Abeta levels measured by ELISA were
      comparable to those reported in mouse models, suggesting that substantially
      greater amounts of soluble Abeta are not required in the rat to generate Abeta
      deposition.

PMID- 18053620
TI  - Antibody response to 7-valent conjugated pneumococcal vaccine in patients with
      chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) is a common adulthood mature B-cell neoplasm.
      Infections are the most important cause of mortality in this condition, and
      Streptococcus pneumoniae has been considered the most important single pathogen.
      We investigated the immunogenicity of 7-valent pneumococcal conjugate vaccine in
      patients with CLL. The study material comprised 52 patients with CLL and 25 age-
      and sex-matched controls. The subjects were vaccinated with Prevenar pneumococcal
      conjugate vaccine. Serum samples were taken for antibody determinations before
      and four weeks after vaccination. Antibody response rates to vaccine antigens
      were lower in patients with CLL compared to controls. However, if the vaccine had
      been administered at an early stage of the disease, i.e. before commencement of
      chemotherapy and the development of hypogammaglobulinaemia, a significant
      vaccination response to at least six antigens was obtained in almost 40% of the
      CLL patients. Our results indicate that early administration of conjugate vaccine
      may be beneficial in CLL.

PMID- 18053621
TI  - Generation of a recombinant Oka varicella vaccine expressing mumps virus
      hemagglutinin-neuraminidase protein as a polyvalent live vaccine.
AB  - We constructed a recombinant varicella-zoster virus (VZV) Oka vaccine strain
      (vOka) that contained the mumps virus (MuV) hemagglutinin-neuraminidase (HN)
      gene, inserted into the site of the ORF 13 gene by using the bacterial artificial
      chromosome (BAC) system in Escherichia coli. Insertion of the HN gene into the
      VZV genome was confirmed by PCR and Southern blot. The infectious virus
      reconstituted from the vOka-HN genome (rvOka-HN) had a growth curve similar to
      the original recombinant vOka without the HN gene. The mumps virus HN protein
      expressed in rvOka-HN infected cells was expressed diffusely in the cytoplasm,
      and modification of the protein was similar to that seen in MuV-infected cells.
      Electron microscopic examination of infected cells revealed that HN was expressed
      on the plasma membrane of the cells but not in the viral envelope, suggesting
      that the tropism of rvOka-HN would be unchanged from that of the original vOka
      strain. Immunization of guinea pigs with rvOka-HN-induced VZV- and HN-specific
      antibodies. Interestingly, the induced antibodies had a strong neutralizing
      activity against virus-cell infections of both MuV and VZV. Therefore, the novel
      varicella vaccine expressing MuV HN protein is suitable as a polyvalent live
      attenuated vaccine against VZV and MuV infections.

PMID- 18053622
TI  - Three years of operational experience from Schauinsland CTBT monitoring station.
AB  - Data from three years of operation of a low-level aerosol sampler and analyzer
      (RASA) at Schauinsland monitoring station are reported. The system is part of the
      International Monitoring System (IMS) for verification of the Comprehensive
      Nuclear-Test-Ban Treaty (CTBT). The fully automatic system is capable to measure
      aerosol borne gamma emitters with high sensitivity and routinely quantifies 7Be
      and 212Pb. The system had a high level of data availability of 90% within the
      reporting period. A daily screening process rendered 66 tentative identifications
      of verification relevant radionuclides since the system entered IMS operation in
      February 2004. Two of these were real events and associated to a plausible
      source. The remaining 64 cases can consistently be explained by detector
      background and statistical phenomena. Inter-comparison with data from a weekly
      sampler operated at the same station shows instabilities of the calibration
      during the test phase and a good agreement since certification of the system.

PMID- 18053623
TI  - Factors influencing health care-seeking behaviours among Mayan women in
      Guatemala.
AB  - OBJECTIVE: to identify and better understand factors that influence care-seeking
      behaviour for women's health among indigenous Mayan populations in the highlands
      of Guatemala. DESIGN: adaptation of qualitative anthropological methods involving
      observations, key informant interviews and focus group discussions (FGDs).
      SETTING: Project Concern International's Casa Materna, Huehuetenango, Guatemala.
      PARTICIPANTS: Interviews and FGDs were conducted among 21 clients (current or
      past) of the Casa Materna and traditional birth attendants; 17 female
      advocates/promoters of the Casa Materna and related services; and 12 male
      advocates, including spouses, non-government organisation staff and community
      health workers. FINDINGS: the following findings emerged from focus group data:
      Women's support groups (WSGs) provided an enabling environment in which women
      could form friendships, bond, discuss concerns about their reproductive health,
      and identify concrete ways of addressing them; Supportive friends, family members
      and advocates influenced women's decisions to seek health care at the Casa
      Materna; Women's decisions to seek care were often associated with their sense of
      self-worth and self-esteem, and women's self-esteem was enhanced by their
      participation in the WSGs; Women's decisions to seek care were influenced by the
      perception that women would be able to access culturally appropriate, safe and
      secure health care services at the Casa Materna; The learned behaviour of
      negotiation with key decision-makers and/or opinion leaders was an effective tool
      for convincing such individuals of the value of accessing facility-based care;
      The proven track record, high quality of services and cultural competence offered
      at the Casa Materna increased the confidence and level of trust of clients and
      their family members about the care that would be received; Couple-based
      education and health promotion were effective techniques for achieving behaviour
      and attitude change among both men and women. KEY CONCLUSIONS: the Casa Materna
      and its community outreach strategy serve an essential purpose in the provision
      of maternity care for the isolated and vulnerable families of the Guatemalan
      highlands, by bridging traditional and Western approaches to health care
      services. The Casa Materna service model plays a critical role in improving
      women's self-efficacy and ultimately strengthening the social fabric that
      characterises this high risk and vulnerable population. IMPLICATIONS FOR
      PRACTICE: the Casa Materna model provides a foundation upon which to bridge and
      strengthen the relationship between community advocates, traditional community
      based health care providers, and the government-funded system of health care. The
      findings of this study should be incorporated into future research to determine
      the potential for bringing the model to scale.

PMID- 18053624
TI  - The influence of metatarsal support height and longitudinal axis position on
      plantar foot loading.
AB  - BACKGROUND: Metatarsal supports are effective at decreasing plantar foot
      pressures at the metatarsal heads, however, little is known about the dependence
      of this decrease upon height and position. METHODS: Barefoot static stance
      pressure measurements were recorded during standing in single limb support
      (n=22). Two metatarsal support heights (5mm, 10mm) were evaluated in six
      positions at 5mm increments (0, 5, 10, 15, 20, 25 mm) proximal to the metatarsal
      heads along the longitudinal axis of the foot. The barefoot condition with no
      metatarsal support served as the control. Mean force was measured for each test
      condition. The findings of this study are limited to the barefoot (unshod)
      condition. FINDINGS: Mean plantar force decreased significantly under the second
      metatarsal head with both 5 and 10mm metatarsal supports compared to the control,
      and 10mm metatarsal support compared with 5mm metatarsal support (P<0.05) while
      no statistically significant differences were noted relative to longitudinal axis
      position. INTERPRETATION: The results of this study suggest that the thickness of
      a metatarsal support is a determinant factor in regulating plantar loading.
      Surprisingly, the longitudinal axis location of a metatarsal support does not
      appear to be as important as clinically presumed since the data showed that the
      force decrease was similar for all positions from 5 to 25 mm. Thus, the orthotic
      induced effect of a metatarsal support seems to have a sizable interaction range
      that has not previously been reported. We speculate that the metatarsal support's
      fulcrum and lift effect can be sustained at a more proximal position due to the
      foot's rigidity as a lever and the manner in which a metatarsal support interacts
      with the plantar aponeurosis.

PMID- 18053625
TI  - Susceptibility to acidic precipitation contributes to the decline of the
      terricolous lichens Cetraria aculeata and Cetraria islandica in central Europe.
AB  - The effective quantum yield of photochemical energy conversion in photosystem II
      (Phi2) was shown to be reduced in the terricolous lichens Cetraria aculeata and
      Cetraria islandica by short-term exposure to aqueous SO2 at pH values occurring
      in the precipitation of areas with high SO2 pollution. Significant reduction of
      Phi2 was found at pH<or=3.3. At pH 2.8, Phi2 was close to zero and did not
      recover within 24 h. This suggests that sensitivity to SO2 (primarily associated
      with epiphytic lichens in the past) has contributed to the decline of both
      species in central Europe. In C. islandica, but not in C. aculeata, thalli with
      the natural content of lichen substances were more tolerant to SO2 than thalli
      where the extracellular lichen substances were extracted before the experiment.
      This supports published results that the depsidone fumarprotocetraric acid, a
      major lichen substance of C. islandica, increases the pollution tolerance in
      lichens.

PMID- 18053626
TI  - The impact of MDR1 polymorphisms on prolactin concentrations in patients treated
      with risperidone.

PMID- 18053627
TI  - Tardive dystonic symptoms associated with aripiprazole treatment.

PMID- 18053628
TI  - Placebo and modafinil effect on sleepiness in obstructive sleep apnea.
AB  - INTRODUCTION: Previous studies have evaluated the effect of modafinil on residual
      excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea
      syndrome (OSAS) under effective CPAP treatment. Even though those trials also
      used placebo groups, we suppose that the placebo effect might influence the
      patients' response to modafinil. METHODS: Twenty sleepy patients with OSAS under
      CPAP treatment were selected. All of them had Epworth Sleepiness Scale (ESS) >10.
      Following baseline evaluation (T1), all subjects were instructed to take placebo
      for 7 days. After this single-blind placebo phase and second evaluation (T2),
      patients were randomly allocated to placebo or modafinil treatment for 21 days in
      a double-blind protocol. Patients underwent a final evaluation (T3) on the last
      day of drug intake. The evaluations at T1, T2 and T3 consisted of: medical and
      laboratory examinations, nocturnal polysomnography, ESS, maintenance of
      wakefulness test (MWT) and complex reaction time (CRT-NY). In addition, in T2 and
      T3 the change of illness severity scale (CGI-C) and the evaluation of quality of
      life (SF-36) were applied. RESULTS: The comparison between the two groups during
      the three periods studied, showed the following results: in the modafinil group,
      ESS score did not change during the initial placebo period, but there was a
      significant reduction during the modafinil treatment period (p=0.0006); in the
      placebo group a significant reduction occurred during the initial placebo period
      (p=0.05), and no further change was observed in the treatment (placebo) period. A
      significant difference was found between the two groups after the placebo period
      (T2) (p=0.02). Three patients (33%) of the modafinil group and 9 patients (81%)
      of the placebo group were classified as placebo-responsive (X2: p=0.039). In the
      treatment period, reaction time was significantly reduced in the modafinil group
      compared to the placebo group (p<0.02). There was a trend toward improvement in
      overall clinical condition and also in some domains of SF-36 in the modafinil
      group. CONCLUSION: In summary, our study confirms that modafinil used
      adjunctively with CPAP therapy improves subjective daytime sleepiness in patients
      with OSAS who were regular users of CPAP therapy but still experienced
      sleepiness. Moreover, it could help in the improvement of objective measures of
      behavioral alertness and reduce functional impairments. The usefulness of a
      blinded placebo period for systematic investigation of placebo role in studies
      based on subjective response is a point that should be considered in this type of
      drug trial.

PMID- 18053629
TI  - Effects of anti-depressants on olfactory sensitivity in mice.
AB  - RATIONALE AND OBJECTIVES: Some studies have underlined a decrease in olfactory
      sensitivity in patients suffering from depression. The present study aims to
      evaluate the effects of current anti-depressant drugs on the olfactory
      sensitivity in mice. METHODS MICE: (N degrees =22) were tested in a Y-maze with a
      choice between an odorant (butanol) or distilled water before and during 3 weeks
      of daily intra-peritoneal injection of either citalopram or clomipramine. Their
      performance was compared with those of a control group (N degrees =11) injected
      with a saline solution. RESULTS: The results showed a significant decrease in
      olfactory sensitivity with both anti-depressants during the three weeks of
      treatment. CONCLUSION: The antidepressant induced alteration in serotonin and/or
      noradrenaline transmission in the olfactory bulb may account for the altered
      olfactory sensitivity observed in this study.

PMID- 18053630
TI  - Formation of hydrogen fluoride by gamma and beta sterilisation in medical devices
      containing perfluoroheptane.
AB  - Infusion of hexadecafluoroheptane, a liquid perfluorocarbon released from
      repaired Althane dialysers was found to be the most probable reason for the
      deaths of 53 dialysis patients reported in the year 2001. This study focuses on
      toxic decomposition products generated due to gamma and beta sterilisation of
      hexadecafluoroheptane. The responsible dialysers were sterilised with a maximum
      dose of 45 kGy gamma irradiation. We investigated the influence of both 20-500
      kGy gamma and beta irradiation on perfluoroheptane. Analysis of the irradiated
      samples verified the decomposition of perfluoroheptane in dependence on the dose
      of irradiation. Beta irradiation resulted in a higher degree of decomposition
      than the same dose of gamma irradiation. As decomposition products, hydrogen
      fluoride, CO2, and one saturated fluorinated hydrocarbon which could not be
      analysed exactly were identified. Even at 20 kGy gamma irradiation hydrogen
      fluoride was detectable. Our results provide evidence that hydrogen fluoride is
      generated as a highly toxic decomposition product when perfluoroheptane is
      sterilised with gamma irradiation as it was applied on the affected dialysers.
      There is no evidence of other toxic degradation products especially
      perfluoroisobutylene. Therefore, hydrogen fluoride or the dissociated fluoride
      ions might act as a toxic agent when medical devices containing liquid
      perfluorocarbons are sterilised by irradiation.

PMID- 18053632
TI  - Naltrexone effect on physiological and subjective response to a cold pressor
      task.
AB  - In this double-blind, cross-over study physiological (i.e. blood pressure, heart
      rate, plasma catecholamine concentrations, plasma cortisol concentrations) and
      subjective (i.e. McGill Pain Questionnaire, positive affect, distress) response
      to a cold pressor task was assessed in 19 subjects 1 h after the administration
      of 50 mg naltrexone and after placebo. Significant differences in plasma
      catecholamine concentrations were found. Plasma epinephrine concentrations
      increased during the 1 h period after naltrexone administration but remained
      largely unchanged after placebo administration. A significant treatment x period
      effect was also found for plasma norepinephrine concentrations. No significant
      differences were found for other measures assessed. Further research is necessary
      to determine the subpopulations in which these effects are of greatest magnitude
      and the long term safety implications of these effects.

PMID- 18053633
TI  - Site localization of membrane-bound proteins on whole cell level using atomic
      force microscopy.
AB  - This study presents molecular recognition method, which is based on specific
      force measurements between modified AFM (atomic force microscopy) tip and
      mammalian cell. The presented method allows recognition of specific cell surface
      proteins and receptor sites by nanometer accuracy level. Here we demonstrate
      specific recognition of membrane-bound Osteopontin (OPN) sites on preosteogenic
      cell membrane. By merging specific force detection map of the proteins and
      topography image of the cell, we create a new image (recognition image), which
      demonstrates the exact locations of the proteins relative to the cell membrane.
      The recognition results indicate the strong affinity between the modified tip and
      the target molecules, therefore, it enables the use of an AFM as a remarkable
      nanoscale tracking tool on the whole cell level.

PMID- 18053634
TI  - The characterization of epithelial and stromal subsets of candidate
      stem/progenitor cells in the human adult prostate.
AB  - OBJECTIVES: Questions regarding the cell source and mechanisms in the initiation
      and progression of prostate cancer are today still open for debate. Indeed, our
      knowledge regarding prostate cell regulation, self-renewal, and
      cytodifferentiation is presently rather limited. In this study, we investigated
      these processes in the normal adult human prostate. METHODS: Dynamic expression
      patterns in prostate stem/progenitor cells, intermediate/transit-amplifying
      cells, and cell lineages were immunohistochemically identified in an in situ
      explant renewal model of the human normal/benign adult prostate (n=6). RESULTS:
      Cells with a basal phenotype proliferated significantly in explant cultures,
      whereas luminal cells went into apoptosis. Results further show down-regulation
      in tissue cultures of the basal and hypothetical stem cell marker Bcl-2 in the
      majority of cells, except in rare putative epithelial stem cells. Investigation
      of established (AC133) and novel candidate prostate stem/progenitor markers,
      including the cell surface receptor tyrosine kinase KIT and its ligand stem cell
      factor (SCF), showed that these rare epithelial cells are AC133(+)/CD133(low)/Bcl
      2(high)/cytokeratin(+)/vimentin(-)/KIT(low)/SCF(low). In addition, we report on a
      stromal population that expresses the mesenchymal marker vimentin and that is
      AC133(-)/CD133(high)/Bcl-2(-)/cytokeratin(-)/KIT(high)/SCF(high). CONCLUSIONS: We
      provide evidence for epithelial renewal in response to tissue culture and for
      basal and epithelial stem/progenitor cell recruitment leading to an expansion of
      an intermediate luminal precursor phenotype. Data further suggest that SCF
      regulates prostate epithelial stem/progenitor cells in an autocrine manner and
      that all or a subset of the identified novel stromal phenotype represents
      prostate stromal progenitor cells or interstitial pacemaker cells or both.

PMID- 18053635
TI  - Editorial comment on: The characterization of epithelial and stromal subsets of
      candidate stem/progenitor cells in the human adult prostate.

PMID- 18053636
TI  - Neoadjuvant sutent induction therapy may effectively down-stage renal cell
      carcinoma atrial thrombi.
AB  - A 75-yr-old previously healthy woman presented with gross hematuria, European
      Cooperative Oncology Group 0, and an 11-cm renal mass with right atrial thrombus.
      The patient refused the sternotomy. She was offered two cycles of sunitinib
      maleate (Sutent) induction therapy to down-stage the thrombus and to reduce the
      extent of the surgery.

PMID- 18053631
TI  - Vasopressin: behavioral roles of an "original" neuropeptide.
AB  - Vasopressin (Avp) is mainly synthesized in the magnocellular cells of the
      hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) whose axons
      project to the posterior pituitary. Avp is then released into the blood stream
      upon appropriate stimulation (e.g., hemorrhage or dehydration) to act at the
      kidneys and blood vessels. The brain also contains several populations of
      smaller, parvocellular neurons whose projections remain within the brain. These
      populations are located within the PVN, bed nucleus of the stria terminalis
      (BNST), medial amygdala (MeA) and suprachiasmatic nucleus (SCN). Since the 1950s,
      research examining the roles of Avp in the brain and periphery has intensified.
      The development of specific agonists and antagonists for Avp receptors has
      allowed for a better elucidation of its contributions to physiology and behavior.
      Anatomical, pharmacological and transgenic, including "knockout," animal studies
      have implicated Avp in the regulation of various social behaviors across species.
      Avp plays a prominent role in the regulation of aggression, generally of
      facilitating or promoting it. Affiliation and certain aspects of pair-bonding are
      also influenced by Avp. Memory, one of the first brain functions of Avp that was
      investigated, has been implicated especially strongly in social recognition. The
      roles of Avp in stress, anxiety, and depressive states are areas of active
      exploration. In this review, we concentrate on the scientific progress that has
      been made in understanding the role of Avp in regulating these and other
      behaviors across species. We also discuss the implications for human behavior.

PMID- 18053637
TI  - Robustness analysis of EGFR signaling network with a multi-objective evolutionary
      algorithm.
AB  - Robustness, the ability to maintain performance in the face of perturbations and
      uncertainty, is believed to be a necessary property of biological systems. In
      this paper, we address the issue of robustness in an important signal
      transduction network--epidermal growth factor receptor (EGFR) network. First, we
      analyze the robustness in the EGFR signaling network using all rate constants
      against the Gauss variation which was described as "the reference parameter set"
      in the previous study [Kholodenko, B.N., Demin, O.V., Moehren, G., Hoek, J.B.,
      1999. Quantification of short term signaling by the epidermal growth factor
      receptor. J. Biol. Chem. 274, 30169-30181]. The simulation results show that
      signal time, signal duration and signal amplitude of the EGRR signaling network
      are relatively not robust against the simultaneous variation of the reference
      parameter set. Second, robustness is quantified using some statistical
      quantities. Finally, a multi-objective evolutionary algorithm (MOEA) is presented
      to search reaction rate constants which optimize the robustness of network and
      compared with the NSGA-II, which is a representation of a class of modern multi
      objective evolutionary algorithms. Our simulation results demonstrate that signal
      time, signal duration and signal amplitude of the four key components--the most
      downstream variable in each of the pathways: R-Sh-G-S, R-PLP, R-G-S and the
      phosphorylated receptor RP in EGRR signaling network for the optimized parameter
      sets have better robustness than those for the reference parameter set and the
      NSGA-II. These results can provide valuable insight into experimental designs and
      the dynamics of the signal-response relationship between the dimerized and
      activated EGFR and the activation of downstream proteins.

PMID- 18053638
TI  - Cytochrome P450s in the development of target-based anticancer drugs.
AB  - Enzymes of the cytochrome P450 (CYP) superfamily are the major determinants of
      half-life and execute pharmacological effects of many therapeutic drugs. In new
      drug discovery research, recombinant (human) CYPs are also used for identifying
      active or inactive metabolites that could lead to increased potency or toxicity
      of a molecule. In addition, CYP inhibition by anticancer drugs might lead to
      adverse drug reactions, multiple-drug resistance, and drug-drug interactions.
      During the discovery and pre-clinical evaluation of a New Chemical Entity (NCE),
      large amounts of purified recombinant CYPs are required for studying metabolism
      and pharmacokinetic parameters. Therefore, present research efforts are focused
      to over-express these human CYPs in bacteria, yeast, insect and mammalian cells,
      followed by their purification on an industrial scale to facilitate
      identification of novel anticancer drugs. This review summarizes the merits and
      limitations of these expression systems for an optimized production of individual
      CYP isoforms, and their usefulness in the discovery and development of target
      based, safe and efficacious NCEs for the treatment of cancer.

PMID- 18053639
TI  - Low hMLH1 expression prior to definitive chemoradiotherapy predicts poor
      prognosis in esophageal squamous cell carcinoma.
AB  - The present study evaluated the pretreatment expression patterns of hMLH1, MDM2,
      p53, and pRb protein to determine whether these could predict the outcome of
      definitive concurrent chemoradiotherapy (CCRT) in 51 patients with stage I-IVa
      esophageal squamous cell carcinoma. High immunoreactivies of hMLH1, MDM2, p53,
      and pRb were detected in 90.2%, 19.6%, 27.5%, and 66.7% of entire patients,
      respectively. High hMLH1 expression was found to favor earlier stage, less
      locoregional failure, and longer cause-specific survival, and all were with
      significance. However, the expressions of MDM2, p53, and pRb were not found to be
      clinically significant. Thirty-three patients with high hMLH1 and pRb expression
      tended to survive longer than four patients with low hMLH1 and pRb expression. We
      suggest that the expression of hMLH1 is a potential marker of tumor response and
      survival. Determinations of this protein expression might be useful for selecting
      esophageal squamous cell carcinoma patients for definitive CCRT.

PMID- 18053640
TI  - The testing of several biological and chemical coupled treatments for Cibacron
      Red FN-R azo dye removal.
AB  - Several biological and chemical coupled treatments for Cibacron Red FN-R reactive
      azo dye degradation have been evaluated. Initially, a two-stage anaerobic-aerobic
      biotreatment has been assessed for different dye concentrations (250, 1250 and
      3135 mg l(-1)). 92-97% decolourisation was attained during the anaerobic
      digestion operating in batch mode. However, no dissolved organic carbon (DOC)
      removal neither biogas production was observed during the process, indicating
      that no methanogenesis occurred. Additionally, according to Biotox and Zahn
      Wellens assays, the anaerobically generated colourless solutions (presumably
      containing the resulting aromatic amines from azo bond cleavage) were found to be
      more toxic than the initial dye as well as aerobically non-biodegradable, thus
      impeding the anaerobic-aerobic biological treatment. In a second part, the use of
      an advanced oxidation process (AOP) like photo-Fenton or ozonation as a chemical
      post-treatments of the anaerobic process has been considered for the complete dye
      by-products mineralisation. The best results were obtained by means of ozonation
      at pH 10.5, achieving a global 83% mineralisation and giving place to a final
      harmless effluent. On the contrary, the tested photo-Fenton conditions were not
      efficient enough to complete oxidation.

PMID- 18053641
TI  - Sorption and desorption studies of chromium(VI) from nonviable cyanobacterium
      Nostoc muscorum biomass.
AB  - This communication presents results pertaining to the sorptive and desorptive
      studies carried out on chromium(VI) removal onto nonviable freshwater
      cyanobacterium (Nostoc muscorum) biomass. Influence of varying the conditions for
      removal of chromium(VI), such as the pH of aqueous solution, the dosage of
      biosorbent, the contact time with the biosorbent, the temperature for the removal
      of chromium, the effect of light metal ions and the adsorption-desorption studies
      were investigated. Sorption interaction of chromium on to cyanobacterial species
      obeyed both the first and the second-order rate equation and the experimental
      data showed good fit with both the Langmuir and freundlich adsorption isotherm
      models. The maximum adsorption capacity was 22.92 mg/g at 25 degrees C and pH
      3.0. The adsorption process was endothermic and the values of thermodynamic
      parameters of the process were calculated. Various properties of the
      cyanobacterium, as adsorbent, explored in the characterization part were chemical
      composition of the adsorbent, surface area calculation by BET method and surface
      functionality by FTIR. Sorption-desorption of chromium into inorganic solutions
      and distilled water were observed and this indicated the biosorbent could be
      regenerated using 0.1 M HNO3 and EDTA with upto 80% recovery. The biosorbents
      were reused in five biosorption-desorption cycles without a significant loss in
      biosorption capacity. Thus, this study demonstrated that the cyanobacterial
      biomass N. muscorum could be used as an efficient biosorbent for the treatment of
      chromium(VI) bearing wastewater.

PMID- 18053642
TI  - Removal of Pb(II) from aqueous solution by oxidized multiwalled carbon nanotubes.
AB  - Oxidized multiwalled carbon nanotubes (MWCNTs) were employed as sorbent to study
      the sorption characteristic of Pb(II) from aqueous solution as a function of
      contact time, pH, ionic strength, foreign ions, and oxidized MWCNTs' contents
      under ambient conditions using batch technique. The results indicate that
      sorption of Pb(II) on oxidized MWCNTs is strongly dependent on pH values, and
      independent of ionic strength and the type of foreign ions. The removal of Pb(II)
      to oxidized MWCNTs is rather quickly and the kinetic sorption can be described by
      a pseudo-second-order model very well. Sorption of Pb(II) is mainly dominated by
      surface complexation rather than ion exchange. The efficient removal of Pb(II)
      from aqueous solution is limited at pH 7-10. X-ray photoelectron spectroscopy
      (XPS) is performed to study the sorption mechanism at a molecular level and
      thereby to identify the species of the sorption processes. The 3-D relationship
      of pH, Ceq and q indicates that all the data of Ceq-q lie in a straight line with
      slope -V/m and intercept C0V/m for the same initial concentration of Pb(II) and
      same content of oxidized MWCNTs of each experimental data.

PMID- 18053643
TI  - Off-site toxic consequence assessment: a simplified modeling procedure and case
      study.
AB  - An assessment of off-site exposure from spills/releases of toxic chemicals can be
      conducted by compiling site-specific operational, geographic, demographic, and
      meteorological data and by using screening-level public-domain modeling tools
      (e.g., RMP Comp, ALOHA and DEGADIS). In general, the analysis is confined to the
      following: event-based simulations (allow for the use of known, constant,
      atmospheric conditions), known receptor distances (on the order of miles or
      less), short time scale for the distances considered (order of 10's of minutes or
      less), gently sloping rough terrain, dense and neutrally buoyant gas dispersion,
      known chemical inventory and infrastructure (used to define source-term), and
      known toxic endpoint (defines significance). While screening-level models are
      relatively simple to use, care must be taken to ensure that the results are
      meaningful. This approach allows one to assess risk from catastrophic release
      (e.g., via terrorism), or plausible release scenarios (related to standard
      operating procedures and industry standards). In addition, given receptor
      distance and toxic endpoint, the model can be used to predict the critical spill
      volume to realize significant off-site risk. This information can then be used to
      assess site storage and operation parameters and to determine the most economical
      and effective risk reduction measures to be applied.

PMID- 18053644
TI  - Adsorption of organic pollutants from coking and papermaking wastewaters by
      bottom ash.
AB  - Bottom ash, a power plant waste, was used to remove the organic pollutants in
      coking wastewater and papermaking wastewater. Particular attention was paid on
      the effect of bottom ash particle size and dosage on the removal of chemical
      oxygen demand (COD). UV-vis spectra, fluorescence excitation-emission matrix
      (FEEM) spectra, Fourier transform infrared (FTIR) spectra, and scanning electron
      microscopic (SEM) photographs were investigated to characterize the wastewaters
      and bottom ash. The results show that the COD removal efficiencies increase with
      decreasing particle sizes of bottom ash, and the COD removal efficiency for
      coking wastewater is much higher than that for papermaking wastewater due to its
      high percentage of particle organic carbon (POC). Different trends of COD removal
      efficiency with bottom ash dosage are also observed for coking and papermaking
      wastewaters because of their various POC concentrations. Significant variations
      are observed in the FEEM spectra of wastewaters after treatment by bottom ash.
      New excitation-emission peaks are found in FEEM spectra, and the fluorescence
      intensities of the peaks decrease. A new transmittance band in the region of 1400
      1420 cm(-1) is observed in FTIR spectra of bottom ash after adsorption. The SEM
      photographs reveal that the surface of bottom ash particles varies evidently
      after adsorption.

PMID- 18053645
TI  - Epinephrine inhibits analgesic tolerance to intrathecal administrated morphine
      and increases the expression of calcium-calmodulin-dependent protein kinase
      IIalpha.
AB  - Activation of hypothalamic-pituitary-adrenal (HPA) axis inhibits development of
      morphine tolerance. Also, the expression of CaMKIIalpha is increased following
      chronic administration of morphine. In the current study, we tried to examine the
      effect of epinephrine, on the development of morphine tolerance; and also
      evaluate the expression of CaMKIIalpha as a molecular index for tolerance
      development. Analgesic tolerance was induced by intrathecal (i.t.) injection of
      morphine 15 microg/rat, twice a day for 5 days. To study the effect of
      epinephrine on development or reversal of morphine tolerance, epinephrine was
      administrated 20 min before morphine injections. Analgesia was assessed using
      tail flick test. Gene expression assays were done using RT-PCR. Following 5 days
      of combined administration of morphine and epinephrine (2, 5 or 10 microg/rat),
      in day 6, morphine produced potent analgesia. Administration of saline and
      morphine during days 1-5, caused reduced analgesic effect of morphine on day 6.
      After tolerance induction during 5 days, co-administration of epinephrine and
      morphine for another 5 days, significantly reversed the tolerance. Both morphine
      and epinephrine increased the expression of CaMKIIalpha. The expression of
      CaMKIIalpha was highly increased following combined administration of epinephrine
      and morphine. Our results showed the inhibition and reversal of analgesic
      tolerance to local administrated morphine by epinephrine. We observed the
      increased expression of CaMKIIalpha without development of morphine tolerance in
      animals treated with combined epinephrine and morphine.

PMID- 18053646
TI  - Intravenous administration of bone marrow stromal cells increases survivin and
      Bcl-2 protein expression and improves sensorimotor function following ischemia in
      rats.
AB  - Intravenous administration of bone marrow stromal cells (MSCs) in animal models
      with focal cerebral ischemia has been found to be effective in attenuating
      neuronal damage. We examined whether intravenously transplanted MSCs alters
      expression of apoptosis-related proteins. Fisher-344 rats were subjected to 90
      min middle cerebral artery occlusion (MCAO). The experimental groups were: (I)
      vehicle group, with intravenous injection of phosphate-buffered saline (PBS) 3h
      after MCAO; and (II) transplant group, with intravenous injection of MSCs
      (3x10(6)cells) 3h after MCAO. Neurological function of rats was evaluated using
      modified neurological severity score (mNSS) and Rotor-rod Motor Test (RMT). Rats
      were sacrificed on 1st, 3rd and 7th days of MCAO, and coronal brain sections were
      stained immunohistochemically to identify the apoptosis-related proteins, namely
      survivin and Bcl-2. We also examined Terminal Deoxynucleotidyl Transferase
      Mediated dUTP-biotin Nick End Labeling (TUNEL)-positive cells on 3rd day of MCAO.
      Functional recovery according to mNSS and RMT was significantly better in the
      transplant group as compared with the vehicle group (P<0.05). Immunohistochemical
      analysis revealed significant expression of survivin on 3rd day and Bcl-2 on 1st
      and 3rd days in the transplant group. The vehicle group displayed significantly
      more TUNEL-positive cells than the transplant group on 3rd day (P<0.05). These
      results suggest that intravenous transplantation of MSCs prevents down-regulation
      of survivin and Bcl-2 preventing apoptosis and cell death in the ischemic brain
      leading to motor and sensory function recovery.

PMID- 18053647
TI  - Neuropeptide co-release with GABA may explain functional non-monotonic
      uncertainty responses in dopamine neurons.
AB  - Co-release of the inhibitory neurotransmitter GABA and the neuropeptide substance
      P (SP) from single axons is a conspicuous feature of the basal ganglia, yet its
      computational role, if any, has not been resolved. In a new learning model, co
      release of GABA and SP from axons of striatal projection neurons emerges as a
      highly efficient way to compute the uncertainty responses that are exhibited by
      dopamine (DA) neurons when animals adapt to probabilistic contingencies between
      rewards and the stimuli that predict their delivery. Such uncertainty-related
      dopamine release appears to be an adaptive phenotype, because it promotes
      behavioral switching at opportune times. Understanding the computational linkages
      between SP and DA in the basal ganglia is important, because Huntington's disease
      is characterized by massive SP depletion, whereas Parkinson's disease is
      characterized by massive DA depletion.

PMID- 18053648
TI  - PLA(2) signaling is involved in calpain-mediated degradation of synaptic
      dihydropyrimidinase-like 3 protein in response to NMDA excitotoxicity.
AB  - Dihydropyrimidinase-like 3 (DPYSL3) is believed to play a role in neuronal
      differentiation, axonal outgrowth and neuronal regeneration, as well as
      cytoskeleton organization. Recently we have shown that glutamate excitotoxicity
      and oxidative stress result in calpain-dependent cleavage of DPYSL3, and that NOS
      plays a role in this process [R. Kowara, Q. Chen, M. Milliken, B. Chakravarthy,
      Calpain-mediated truncation of dihydropyrimidinase-like 3 protein (DPYSL3) in
      response to NMDA and H2O2 toxicity, J. Neurochem. 95 (2005) 466-474; R. Kowara,
      K.L. Moraleja, B. Chakravarthy, Involvement of nitric oxide synthase and ROS
      mediated activation of L-type voltage-gated Ca(2+) channels in NMDA-induced
      DPYSL3 degradation, Brain Res. 1119 (2006) 40-49]. The present study investigates
      the involvement of PLA(2) signaling in NMDA-induced DPYSL3 degradation. Exposure
      of rat primary cortical neurons (PCN) to PLA(2) and COX-2 inhibitors
      significantly prevented NMDA-induced DPYSL3 degradation. Since the metabolic
      product of PLA(2) signaling, PGE(2), which augments toxic effect of NMDA, is
      known to stimulate cAMP, the effect of adenyl cyclase activator (forskolin plus
      IBMX) and inhibitor (MDL12,300) on NMDA-induced DPYSL3 degradation was tested.
      Our data indicate that the activation of adenyl cyclase contributes to NMDA
      induced DPYSL3 degradation. Furthermore, cAMP-dependent protein kinase (PKA)
      inhibitor PKI (14-22) provided additional evidence of PKA involvement in NMDA
      induced DPYSL3 degradation. In summary, the obtained data show the contribution
      of PLA(2) signaling to NMDA-induced calpain activation and subsequent degradation
      of synaptic protein DPYSL3.

PMID- 18053649
TI  - Performance limits of electron holography.
AB  - Transmission electron microscopy is wave optics. The object exit wave contains
      the full object information. However, in the usual intensity images, recorded
      either in real space or in Fourier space, the phases are missing. In many
      applications at medium and at high resolution, electron holography has shown its
      unique ability of solving the "missing phase problem" and utilizing the recovered
      phase for complete interpretation of the object structure. The question is "What
      are the performance limits?" with respect to field of view, lateral resolution
      and signal resolution. In this article, the performance limits are derived and
      discussed.

PMID- 18053650
TI  - High-resolution scanning near-field EBIC microscopy: application to the
      characterisation of a shallow ion implanted p+-n silicon junction.
AB  - High-resolution electron beam induced current (EBIC) analyses were carried out on
      a shallow ion implanted p+-n silicon junction in a scanning electron microscope
      (SEM) and a scanning probe microscope (SPM) hybrid system. With this scanning
      near-field EBIC microscope, a sample can be conventionally imaged by SEM, its
      local topography investigated by SPM and high-resolution EBIC image
      simultaneously obtained. It is shown that the EBIC imaging capabilities of this
      combined instrument allows the study of p-n junctions with a resolution of about
      20 nm.

PMID- 18053651
TI  - Interleukin-1beta enhances the action of bradykinin in rat myenteric neurons
      through up-regulation of glial B1 receptor expression.
AB  - Interleukin (IL)-1beta and tumor necrosis factor alpha (TNFalpha) are released
      under pathological conditions in the gastrointestinal tract such as inflammatory
      bowel diseases (IBD). We examined the effects of IL-1beta and TNFalpha on
      bradykinin (BK) -induced increases in the intracellular Ca(2+) concentration
      ([Ca(2+)]i) and prostaglandin (PG) E(2) release in neonatal rat myenteric plexus
      cells. BK evoked a [Ca(2+)]i increase in myenteric neurons and glial cells, both
      of which were potentiated by treatment with IL-1beta but not TNFalpha. In both
      cell types, the [Ca(2+)]i responses to BK were abolished by D-Arg(0)[Hyp(3),
      Thi(5), D-Tic(7), Oic(8)]-BK (HOE140), a B2R antagonist, but not affected by des
      Arg(9)-HOE140, a B1R antagonist. After culture with IL-1beta, however, the B1R
      antagonist suppressed the BK-induced [Ca(2+)]i increase. Only in glial cells did
      the B1R agonists des-Arg(9)-BK and BK fragment 1-8 evoke a [Ca(2+)]i rise in a
      dose-dependent manner. Real time RT-PCR and immunocytochemical analyses showed
      that IL-1beta treatment increased expression of B1R mRNA in myenteric plexus
      cells and B1R protein in glial cells, respectively. Either indomethacin or an EP1
      receptor antagonist suppressed the increased [Ca(2+)]i response to BK invoked by
      treatment with IL-1beta. IL-1beta treatment increased BK-induced PGE(2) release
      from cultured myenteric plexus cells. These results suggest that IL-1beta
      promotes up-regulation of B1R expression in glial cells, resulting in the
      potentiation of neural responses to BK through the elevation of PGE(2) released
      from glial cells. The alteration of phenotypes of glial cells may be the cause of
      the changes in neural function in the enteric nervous system in IBD.

PMID- 18053652
TI  - Relationship between prolactin secretion, and plasma risperidone and 9
      hydroxyrisperidone concentrations in adolescents with schizophreniform disorder.
AB  - BACKGROUND: Treatment with the atypical antipsychotic risperidone can result in
      elevated prolactin levels. To date, the relationships between plasma
      concentrations of prolactin, risperidone and its active 9-hydroxy-metabolite have
      been little investigated in adolescents with psychosis. METHODS: Prolactin levels
      were determined at baseline in 16 hospitalized drug-naive adolescents meeting DSM
      IV criteria for schizophreniform disorder. Prolactin, risperidone, 9
      hydroxyrisperidone levels were subsequently determined after 3 weeks of oral
      risperidone treatment. RESULTS: Compared with pretreatment values, prolactin
      levels at endpoint were significantly increased (p<0.00001) and correlated with
      risperidone doses (r=0.58, N=16, p<0.02), and plasma levels of risperidone
      (r=0.60, N=16, p<0.02) and 9-hydroxyrisperidone (r=0.54, N=16, p=0.03).
      CONCLUSIONS: These data suggest that risperidone's effect on prolactin release is
      dose-dependent in adolescents and is linked to both plasma risperidone and 9
      hydroxyrisperidone concentrations.

PMID- 18053653
TI  - Use of other tobacco products among U.S. adult cigarette smokers: prevalence,
      trends and correlates.
AB  - This paper examines the trends in concurrent use of cigarettes and other tobacco
      and sociodemographic variables associated with concurrent use among adult
      cigarette smokers in the United States. Data from the 1995/96, 1998, 2000, and
      2001/02 Tobacco Use Supplements to the Current Population Survey were used to
      estimate concurrent use of tobacco among cigarette smokers among adults ages 18
      years and older (n for all 4 survey groups=552,804). Concurrent use of tobacco
      fluctuated over the survey periods for current smokers and ranged from 3.7% in
      1995/96 to 7.9% in 1998. Results from the multivariate logistic regression
      indicate that male current, daily, and intermittent smokers had substantially
      higher odds of concurrent use (OR=12.9, 11.7, 17.2, respectively) than their
      female counterparts. Age, race/ethnicity, geographic region, income, and survey
      years were significantly associated with concurrent use among current and daily
      smokers; for intermittent smokers, these variables and occupation were
      significantly associated with concurrent use. The strongest correlates for
      multiple tobacco use among cigarettes smokers were being male and Non-Hispanic
      White. These factors should be considered when planning tobacco prevention and
      control efforts. In addition, surveillance efforts should continue to monitor
      changes in concurrent use and further investigate the increased risk of cancer
      among smokers who also use other forms of tobacco.

PMID- 18053654
TI  - May head-injured patients with thinner skull bones have a better prognosis?

PMID- 18053655
TI  - An evolutionary model of premenstrual syndrome.
AB  - PMS has existed at least since the beginning of medical writing, and is estimated
      to affect large proportions of women worldwide. But the etiology remains unknown,
      diagnostic definition and methods vary tremendously, and treatment is wholly
      symptom-oriented. This poor state of understanding has been attributed to a lack
      of theoretical perspective. The current work provides such a theoretical
      perspective from an evolutionary paradigm. PMS is not evolutionarily adaptive in
      and of itself. Rather, it is part of a cyclic pattern that results from the
      cessation of heightened, positive physical and sociobehavioral states that are
      evolutionarily favored during the fertile phase of the menstrual cycle for some
      women. When the advantage of these positive states diminishes, they cease,
      causing relatively lower states that are subjectively experienced as symptoms. In
      its clinical extreme, this is PMS. However, eons of evolution would result in
      modern women who are choosy about the conditions under which they reproduce.
      Thus, women whose conditions suggest a high probability of successful immediate
      reproduction are expected to experience the heightened, positive states during
      the fertile phase of the menstrual cycle to attract mates and fertilizations;
      these women will experience symptoms premenstrually. But women whose conditions
      suggest a low probability of successful immediate reproduction are expected to
      experience the heightened, positive states during the premenstruum to retain
      mates, accrue or maintain resources, and/or otherwise improve their conditions;
      these women will experience symptoms during the fertile phase of the menstrual
      cycle ("pseudo-PMS"). In addition, the heightened states are expected to shift in
      response to changes in conditions throughout women's lives, being expressed at
      whatever point is most evolutionarily beneficial given current conditions. This
      suggests that our conceptualization of PMS should be reframed within a
      facultative (condition-sensitive), evolutionary model. It also generates
      predictions both within- and between women that should elucidate the syndrome.

PMID- 18053656
TI  - Lavender bath oil reduces stress and crying and enhances sleep in very young
      infants.
AB  - Very young infants were given a bath with or without lavender-scented bath oil.
      The mothers in the lavender bath oil group were more relaxed, smiled and touched
      their infants more during the bath. Their infants looked at them a greater
      percentage of the bath time and cried less and spent more time in deep sleep
      after bath. The cortisol levels of this group of mothers and infants
      significantly decreased, confirming the behavioral data showing increased
      relaxation of the mothers and their infants. These findings support a body of
      research showing the relaxing and sleep-inducing properties of lavender aroma.

PMID- 18053657
TI  - Fenvalerate inhibits progesterone production through cAMP-dependent signal
      pathway.
AB  - Fenvalerate is a widely used synthetic pyrethroid insecticide and is known to
      impede the male reproductive function. However, the mechanisms remain to be
      elucidated. In this study, mouse Leydig tumor cells (MLTC-1) were used to
      investigate the effects of fenvalerate on progesterone production. Fenvalerate
      treatment inhibited progesterone secretion induced by human chorionic
      gonadotropin (hCG), cholera toxin (CT) or forskolin and decreased cAMP levels
      induced by hCG, but not by CT or forskolin, which suggested a repaired site on
      the upstream components of G protein or G protein per se by fenvalerate in the
      cAMP-mediated signal pathway. Furthermore, the addition of cAMP analog, 8-Br
      cAMP, could not reverse fenvalerate-suppressed progesterone synthesis, indicating
      that fenvalerate interfered with the downstream molecules of cAMP. In addition,
      fenvalerate decreased steroidogenic acute regulatory protein (StAR) mRNA and
      protein levels, and also profoundly inhibited the activity of P450 side chain
      cleavage enzyme (P450scc) which was consistent with the decreased expression of
      P450scc mRNA and protein in MLTC-1 cells. These results suggested that
      fenvalerate might inhibit progesterone production by attenuating cAMP generation
      and inhibiting StAR expression and P450scc activity.

PMID- 18053658
TI  - Modelling drug dissolution from controlled release products using genetic
      programming.
AB  - This study has investigated and compared genetic programming (GP) - a method of
      automatically generating equations that describe the cause-and-effect
      relationships in a system - and statistical methods for modelling two controlled
      release formulations--a matrix tablet and microspheres. With the improved GP
      models exhibiting comparable predictive power, as well as simpler equations in
      some cases, the results obtained indicate that GP can be considered as an
      effective and efficient method for modelling controlled release formulations.

PMID- 18053659
TI  - Voriconazole into PLGA nanoparticles: improving agglomeration and antifungal
      efficacy.
AB  - This study is concerned with preparing PLGA nanoparticles loaded with
      voriconazole (PNLV), investigating the burst release and agglomeration of PNLV,
      and also evaluating antifungal efficacy of PNLV compared with voriconazole (VRC).
      The emulsion-solvent evaporation technique for nanoparticles and tests against
      fungi were completed. The amount of VRC in PNLV with sodium hexametaphosphate was
      2.01+/-0.27%, and burst release of PNLV was reduced by about 33% using 20%
      ethanol solution (n=3). The mean D(50) of PNLV with or without this salt was
      132.8 nm and 6.3 microm, respectively (n=5). In vitro; the fungal numbers treated
      with PNLV (3.5 mg/ml, equal amount calculated by VRC) and VRC (70 microg/ml) in
      tubes at the day 7 were 5.74 log(10) and 6.72 log(10), respectively (P<0.05). In
      vivo; the fungal burden treated with PNLV and VRC in tissue from mice kidneys at
      day 7 after administration was 0.64 log(10) and 2.61 log(10), respectively (5
      mg/kg, P<0.001). The hematoxylin-eosin stain in mice kidney showed that the
      pathological lesions treated with PNLV were relieved in contrast with those with
      VRC. These results suggest that the emulsion-solvent evaporation process is
      feasible in preparing PNLV. Moreover, ethanol solution decreased burst release
      and Na-HMP inhibited agglomeration. PNLV could improve the VRC antifungal
      efficacy.

PMID- 18053660
TI  - Distribution of nobiletin chitosan-based microemulsions in brain following i.v.
      injection in mice.
AB  - The purpose of this study was to characterize the in vitro properties of a number
      of chitosan-based microemulsions containing nobiletin and determine its
      distribution in mice brain following i.v. administration. The phase behavior and
      properties of chitosan-based microemulsions were investigated in a pseudo-ternary
      system composed of polyoxyethylene 35 castor oil/benzyl alcohol/medium-chain
      triglyceride/tea oil/water with the chitosan. The droplet sizes were found to be
      smaller than 25 nm by photo correlation spectrometer. The nobiletin-loaded
      hyaluronic acid chitosan-based microemulsion (HAC-ME) carried negative charge and
      nobiletin-loaded hydrochlorate chitosan-based microemulsion (HCC-ME) carried
      positive charge. The concentrations of nobiletin in tissues were determined by
      HPLC after i.v. administration of HAC-ME, nobiletin-loaded microemulsion (ME),
      HCC-ME and nobiletin solution. Based on AUC(0-t), MRT and C(max), HAC-ME
      delivered more nobiletin to the brain compared to nobiletin solution, ME and HCC
      ME. The long-circulation effect might contribute to the higher AUC(0-t) for HAC
      ME in brain. On the other hand, the AUC(0-t) in plasma and brain after i.v.
      administration of HCC-ME were not significantly increased relative to ME. These
      results indicate that HAC-ME may be presented as potential candidates for
      delivering more drugs into the brain.

PMID- 18053662
TI  - Effect of bicellar systems on skin properties.
AB  - Bicelles are discoidal aggregates formed by a flat dimyristoyl-glycero
      phosphocholine (DMPC) bilayer, stabilized by a rim of dihexanoyl-glycero
      phosphocholine (DHPC) in water. Given the structure, composition and the
      dimensions of these aggregates around 10-50 nm diameter, their use for topical
      applications is a promising strategy. This work evaluates the effect of DMPC/DHPC
      bicelles with molar ratio (2/1) on intact skin. Biophysical properties of the
      skin, such as transepidermal water loss (TEWL), elasticity, skin capacitance and
      irritation were measured in healthy skin in vivo. To study the effect of the
      bicellar systems on the microstructure of the stratum corneum (SC) in vitro,
      pieces of native tissue were treated with the aforementioned bicellar system and
      evaluated by freeze substitution applied to transmission electron microscopy
      (FSTEM). Our results show that bicelles increase the TEWL, the skin elastic
      parameters and, decrease skin hydration without promoting local signs of
      irritation and without affecting the SC lipid microstructure. Thus, a
      permeabilizing effect of bicelles on the skin takes place possibly due to the
      changes in the phase behaviour of the SC lipids by effect of phospholipids from
      bicelles.

PMID- 18053661
TI  - Effect of O-acylmenthol on transdermal delivery of drugs with different
      lipophilicity.
AB  - To develop more effective compounds as enhancers, O-acylmenthol derivatives which
      were expected to be enzymatically hydrolyzed into nontoxic metabolites by
      esterases in the living epidermis were synthesized from l-menthol and
      pharmaceutical excipient acids (lactic acid, cinnamic acid, salicylic acid and
      oleic acid) in this study. Their promoting activity on the percutaneous
      absorption of five model drugs, 5-fluorouracil (5-FU), isosorbide dinitrate
      (ISDN), lidocaine (LD), ketoprofen (KP), and indomethacin (IM), which were
      selected based on their lipophilicity represented by log K(O/W), were tested in
      vitro across full thickness rat skin with each of the evaluated drugs in
      saturated donor solution. 2-Isopropyl-5-methylcyclohexyl 2-hydroxypanoate (M-LA)
      provided the highest increase of accumulation of 5-FU (3.74-fold) and LD (4.19
      fold) in the receptor phase while 2-isopropyl-5-methylcyclohexyl cinnamate (M-CA)
      was ineffective for most of the drugs; Both 2-isopropyl-5-methylcyclohexyl 2
      hydroxybenzoate (M-SA) and (E)-2-isopropyl-5-methylcyclohexyl octadec-9-enoate (M
      OA) had better promoting effects on the drugs with low water-solubility. The four
      O-acylmenthol enhancers produced parabolic relationship between the lipophilicity
      (log K(O/W)) of the model drugs (5-FU, ISDN, KP, IM) and their enhancement ratio
      of the permeation coefficient (ER(P)), indicating that the lipophilicity of the
      penetrants has significant effect on the permeation results, r = 0.989 (P=0.144)
      for M-LA, r = 0.965 (P = 0.216) for M-CA, r = 0.786 (P = 0.630) for M-SA, and r =
      0.996 (P = 0.088) for M-OA.

PMID- 18053663
TI  - Polysaccharides with complement fixing and macrophage stimulation activity from
      Opilia celtidifolia, isolation and partial characterisation.
AB  - AIM OF THE STUDY: The present study is aimed to determine the bioactivity and
      structure of polysaccharides present in the leaves from the Malian medicinal
      plant Opilia celtidifolia [Guill. & Perr. Endl. ex Walp (Opiliaceae)]. MATERIALS
      AND METHODS: The polysaccharides from the leaves of Opilia celtidifolia were
      isolated from water extracts of the leaves using gelfiltration and anion exchange
      chromatography giving the fractions Oc50A1 and Oc50A2. Monosaccharide composition
      was determined by gas chromatography of the derived TMS-derivatives of the methyl
      glycosides. Linkages were determined of the partly methylated, partly acetylated
      alditol acetates obtained after a process including reduction, methylation,
      hydrolysis, reduction and acetylation followed by GC-MS. Effects on the
      complement system and the macrophages were determined using specific methods
      aimed for studying those activities. RESULTS: The polysaccharide fractions
      isolated from the leaves of Opilia celtidifolia has high complement fixing
      activity and induce nitrite oxide release from macrophages in a dose dependent
      manner. The fractions had an ICH50 of 0.5 and 0.9 microg/ml respectively in the
      complement fixing assay. They induced the release of 7.2 and 7.3 microM of
      nitrite oxide from macrophages respectively at a dose of 100 microg/ml. The
      monosaccharide composition in Oc50A1 and Oc50A2, analysed, showed the presence of
      arabinose (26.7 and 13.2%), galactose (31.5 and 28%) and galacturonic acid (5.3
      and 7.8%) respectively. The Yariv test confirmed the presence of arabinogalactan
      type II in both fractions. Structural analyses did also show the presence of
      terminal and 1-4 linked galacturonic acid and terminal and 1-2 linked rhamnose.
      Endo-polygalacturonanase treatment was performed to isolate the heavily
      substituted parts of the polysaccharides. These parts contained the same
      monosaccharides in similar proportion, and showed stronger dose dependent
      complement fixing activity and also stimulated macrophages to release nitrite
      oxide. CONCLUSIONS: The leaves of Opilia celtidifola contains polysaccharides of
      pectic type that have both complement fixing and macrophage stimulating activity.

PMID- 18053664
TI  - Ethnobotanical survey of Akwa Ibom State of Nigeria.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plants employed in the
      ethnomedicine of Akwa Ibom State of Nigeria are studied. AIM OF THE STUDY: The
      survey aims at identifying and documenting the plants used amongst the indigenes
      of Akwa Ibom State. MATERIALS AND METHODS: Using ethnobotanical survey list,
      information is gathered through personal interviews with traditional medical
      practitioners, community elders and patients. RESULTS: A total of 114 medicinal
      plant species representing 102 genera and 54 families employed in the traditional
      medical practice of the people of Akwa Ibom State, Nigeria are recorded from 930
      homes. Ailments such as skin diseases, malaria, gonorrhoea and haemorrhoids are
      mostly treated with the medicinal plants. Details pertaining to the preparation
      and administration of plant drugs are provided. CONCLUSIONS: The survey provides
      a veritable source of information for traditional medical practitioners and
      medicinal plant researchers. These medicinal plants may be incorporated into the
      healthcare delivery system of the country.

PMID- 18053665
TI  - Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis
      paniculata extract and andrographolide.
AB  - The inhibitory effect of Andrographis paniculata extract (APE) and
      andrographolide (AND), the most medicinally active phytochemical in the extract,
      on hepatic cytochrome P450s (CYPs) activities was examined using rat and human
      liver microsomes. For this purpose, CYP1A2-dependent ethoxyresorufin-O
      deethylation, CYP2B1-dependent benzyloxyresorufin-O-dealkylation, CYP2B6
      dependent bupropion hydroxylation, CYP2C-dependent tolbutamide hydroxylation,
      CYP2E1-dependent p-nitrophenol hydroxylation and CYP3A-dependent testosterone 6
      beta-hydroxylation activities, were determined in the presence and absence of APE
      or AND (0-200 microM). APE inhibited ethoxyresorufin-O-deethylation activity in
      rat and human liver microsomes, with apparent Ki values of 8.85 and 24.46 microM,
      respectively. In each case, the mode of inhibition was noncompetitive. APE also
      inhibited tolbutamide hydroxylation both in rat and human microsomes with
      apparent Ki values of 8.21 and 7.51 microM, respectively and the mode of
      inhibition was mixed type. In addition, APE showed a competitive inhibition only
      on CYP3A4 in human microsomes with Ki of 25.43 microM. AND was found to be a weak
      inhibitor of rat CYP2E1 with a Ki of 61.1 microM but did not affect human CYP2E1.
      In conclusion, it cannot be excluded from the present study that APE could cause
      drug-drug interactions in humans through CYP3A and 2C9 inhibition.

PMID- 18053666
TI  - Intranasal complications in women with osteoporosis under treatment with nasal
      calcitonin spray: case reports and review of the literature.
AB  - OBJECTIVE: To describe the nasal side effects of postmenopausal women suffering
      from osteoporosis and being treated with intranasal calcitonine (InC). METHOD:
      Two women who presented with nasal complaints, were diagnosed as having nasal
      septum perforation and septum-concha inferior synechiae respectively. Both were
      receiving treatment with InC for postmenopausal osteoporosis. A medline search
      for similar side effects of InC revealed a range of nasal symptoms and several
      factors that could induce these symptoms. RESULTS: Exclusion of other causative
      conditions leads us to attribute the nasal findings to the use of InC. The
      literature mentions mild and usually reversible side effects from use of InC.
      Substances included in the calcitonine spray (preservatives, accelerators of
      absorption), the development of antibodies against the hormone and possible
      implication of coexisting diseases or medications to the provocation of nasal
      side effects, are discussed. CONCLUSIONS: Intranasal administration of
      calcitonine is an established therapy for postmenopausal osteoporosis and other
      skeletal diseases. The side effects from its use are commonly local, mild and
      transient, but there is not sufficient information on how this process begins. An
      ENT examination before and during therapy with InC would be beneficial to
      patients for the recognition and prevention of serious side effects.

PMID- 18053667
TI  - New findings in gene knockout, mutant and transgenic mice.
AB  - During the past year, some novel genetic modifications were shown to alter the
      lifespan of mice, thus expanding the list of genes and physiological processes
      that influence mammalian aging. Considerable progress was also made in
      identifying putative mechanisms of extended longevity in previously described
      gene knockouts, mutants and transgenics. In addition, new leads concerning
      mechanisms of aging were derived from studies of gene knockout mice in which
      aging is accelerated. Among the important findings from the period July 2006 to
      July 2007: Core body temperature was shown to influence longevity in homeothermic
      animals; a Surf1 gene knockout extended lifespan in mice; separate studies using
      Little and Snell dwarf mice found stress resistance enhancements correlated with
      longevity gains; and mice heterozygous for deletion of insulin receptor substrate
      2 (IRS-2) lived longer than normal animals, while animals with homozygous or
      heterozygous deletion of IRS-2 selectively in the brain exhibited comparable
      extension of lifespan and various symptoms of delayed aging.

PMID- 18053668
TI  - Interactions between injury, stress resistance, reproduction, and aging in
      Drosophila melanogaster.
AB  - An important aspect of the aging process in Drosophila melanogaster is the
      natural loss of antennae, legs, bristles, and parts of wings with age. These
      injuries lead to a loss of hemolymph, which contains water and nutrients. Stress
      resistant lines of D. melanogaster are sometimes longer-lived than the
      populations from which they are derived. One hypothesis tested here is that
      increased stress-resistance fosters longevity because it allows fruit flies to
      cope with the loss of hemolymph due to injury to the aging fly. We tested the
      effects of surgically induced injury on the aging and reproduction of five
      replicate populations. We then tested the effects of injury on populations that
      had been selected for different levels of stress resistance and on control
      populations. Injury affected aging more in males than in females, in part because
      of a counter-balancing reduction in female reproduction brought about by injury.
      More specifically, injury reduced female fecundity and male virility. Injury
      significantly reduced the starvation resistance in some groups of flies, but not
      in others. These findings undermine any simple interpretation of the interactions
      between injury, reproduction, and aging based on stress resistance. But they do
      indicate the existence of significant interactions between these biological
      processes, interactions that should be resolved in greater mechanistic detail
      than has been managed here.

PMID- 18053669
TI  - Downregulation of plasma insulin levels and hepatic PPARgamma expression during
      the first week of caloric restriction in mice.
AB  - Calorie restriction extends lifespan by decreasing the rate of tumor formation,
      an effect occurring within 8 weeks of initiating a restricted diet. Our goal was
      to define how the first weeks of a calorie restricted diet (60% of ad libitum
      calories) affects putative mediators of the calorie restriction phenotype,
      focusing on regulators of fatty acid biosynthesis. In C57Bl/6 mice, insulin
      decreased over 50% (p<0.05) during the first week of calorie restriction whereas
      IGF-1 was unaffected. In the liver, PPARgamma mRNA fell to 13% of baseline after
      1 week of calorie restriction (p<0.05), whereas hepatic SREBP-1c and SIRT1 mRNA
      levels were unaffected. No changes in abdominal or subcutaneous adipose tissue
      were observed until after 4 weeks of caloric restriction. We conclude that
      calorie restriction-induced decreases in insulin and hepatic PPARgamma are rapid
      enough to support a role for these molecules in triggering the initial phase of
      the calorie restriction phenotype.

PMID- 18053670
TI  - Distribution and metabolism of gastrodin in rat brain.
AB  - Gastrodin is the major and bioactive component in Tianma (Gastrodia elata Bl.)
      and has sedative, anticonvulsive and neuroprotective effects. Since little is
      known about its neuropharmacokinetics and brain metabolism, this study was
      undertaken to investigate the kinetic inter-relationship of gastrodin in rat
      plasma, cerebrospinal fluid (CSF) and brain microdialysate (frontal cortex,
      hippocampus, thalamus and cerebellum). Gastrodin was administered via the femoral
      vein at a dose of 200mg/kg, and blood, CSF and brain microdialysate were
      collected at timed intervals for the measurement of gastrodin concentrations by
      high-performance liquid chromatography. The samples were analyzed on a Diamonsil
      C18 column (5 microm, 250 mm x 4.6mm i.d.) with a mobile phase consisting of
      acetonitrile-water (5% acetonitrile for brain microdialysate, 2.5% acetonitrile
      for plasma and CSF), and detected with a UV detector at 221 nm. The distribution
      of gastrodin in rat showed that levels of gastrodin declined rapidly after drug
      administration, and the entry of gastrodin into the brain was rapid. However, the
      ratios of AUC(brain)/AUC(plasma) were not high. The individual ratios of the AUC
      in the CSF, frontal cortex, hippocampus, thalamus and cerebellum to the AUC in
      the plasma were 4.8+/-2.4%, 3.3+/-1.2%, 3.0+/-0.7%, 3.3+/-1.3% and 6.1+/-1.9%,
      respectively. The AUC in the cerebellum was significantly higher than that in
      other brain regions (P<0.05). The concentrations of p-hydroxybenzyl alcohol, the
      main metabolite of gastrodin, were very low both in the CSF and plasma.

PMID- 18053671
TI  - Density mapping and chemical component calibration development of four-component
      compacts via terahertz pulsed imaging.
AB  - The purpose of this research was to investigate suitable procedures for
      generating multivariate prediction vectors for quantitative composition and
      density analysis of intact solid oral dosage forms using terahertz pulsed imaging
      (TPI) spectroscopy. Both frequency- (absorbance and refractive index) and time
      domain data are presented. A set of calibration and prediction samples were
      created according to a quaternary mixture design with five levels of compaction
      at each concentration design point. Calibration models were generated by partial
      least-squares, type II (PLS-2) regression of the TPI spectra against nominal
      composition and relative density reference measurements. Quantitative frequency
      domain composition calibration models were created for all crystalline components
      (R(2)>0.90), but the calibration models for individual amorphous components
      (R(2)<0.76) did not perform as well in testing. Combining both amorphous
      components into a single component variable for regression resulted in lower
      error statistics and equally good predictions of crystalline components. A non
      linear attenuation of time-domain spectra was observed as a function of
      compaction force, which corresponded to compact density predictions (R(2)=0.948).
      While refractive index spectra were sensitive to density (R(2)=0.937), the
      absorbance spectra were not. Surface density maps were prepared based on
      refractive index calibrations.

PMID- 18053672
TI  - Control and analysis of alkyl esters of alkyl and aryl sulfonic acids in novel
      active pharmaceutical ingredients (APIs).
AB  - This article reviews current regulatory guidelines and relevant scientific
      literature pertaining to the control and analysis of potential genotoxic
      impurities (PGIs) in new active pharmaceutical ingredients (APIs) with specific
      reference to a certain sub-class of PGIs, namely alkyl esters of alkyl and aryl
      sulfonic acids. Sulfonic acids are very important in pharmaceutical R&D employed
      both as counter-ions in the formation of acid-addition salts and also as reagents
      and catalysts in the synthesis of new drug substances. The article reviews the
      evolution of analytical methodology from early studies in the mid 1970s through
      development of direct injection GC and HPLC methods to liquid-liquid/solid phase
      extraction and headspace based techniques coupled to HPLC and GC methodologies
      employing UV and MS detection to new derivatisation-based techniques. The paper
      also reflects on the significant challenges in developing robust analytical
      methodology capable of the trace determination of sulfonate esters, the
      challenges in transferring methodology from R&D to QC labs and on the cost of
      inappropriate limits for genotox impurities. In so doing, the authors seek to
      inform the debate that the control of genotoxic impurities should be driven
      primarily by safety and risk/benefit considerations rather than by state-of-the
      art analytical and process chemistry capabilities that drive controls to levels
      'as low as practicable' regardless of the risk/safety requirements.

PMID- 18053673
TI  - Multifocal pelvic abscesses and osteomyelitis from community-acquired methicillin
      resistant Staphylococcus aureus in a 17-year-old basketball player.
AB  - A 17-year-old female basketball player suffered from cutaneous abscesses, which
      complicated into a systemic progression to osteomyelitis and simultaneous
      iliopsoas and piriformis abscesses, adjacent to the sacroiliac joint. The
      causative agent was community-acquired methicillin-resistant Staphylococcus
      aureus with multilocus sequence type 30, spa19, and SCCmecIVc. The clinical
      importance of this genotype is discussed.

PMID- 18053674
TI  - Frequency of 1st- and 2nd-step topoisomerase mutations in Streptococcus
      pneumoniae following levofloxacin and moxifloxacin exposure.
AB  - Seven Streptococcus pneumoniae isolates were exposed to inhibitory concentrations
      of levofloxacin and moxifloxacin in antibiotic-containing agar dilution plates.
      Colony counts were used to calculate the frequency of mutation. DNA was sequenced
      to detect mutations in the quinolone resistance-determining regions of the gyrA,
      gyrB, parC, and parE genes. The wild-type S. pneumoniae isolate developed a parC
      mutation after exposure to levofloxacin more frequently than it developed a gyrA
      mutation after exposure to moxifloxacin. The 1st-step gyrA mutant developed a 2nd
      step gyrA-parC mutation more frequently after exposure to levofloxacin.
      Conversely, the transformation from a 1st-step parC mutant to a 2nd-step parC
      gyrA mutant occurred more frequently following exposure to moxifloxacin. Our data
      suggest that the occurrence of a 2nd mutation will be contingent on the location
      of the 1st mutation and the preferential binding site of the fluoroquinolone that
      drives the transformation from 1st- to 2nd-step mutant.

PMID- 18053675
TI  - Purulent pericarditis caused by nontypeable Haemophilus influenzae in a pediatric
      patient.
AB  - We report the 1st case of purulent pericarditis due to nontypeable Haemophilus
      influenzae in an immunocompetent 2-year-old male, which was successfully treated
      with surgical drainage, debridement, and antimicrobial therapy. The shifting
      microbial epidemiology of this disease, associated with changes in community
      health care practices, and the increasing virulence of this organism are
      discussed.

PMID- 18053676
TI  - Computer-based decision making in medicine: A model for surgery of colorectal
      liver metastases.
AB  - AIMS: Seeking the best available treatment for patients with colorectal liver
      metastases may be complex due to the interpretation of many variables. In this
      study conjoint analysis is used to develop a decision model to help clinicians
      selecting patients eligible for surgery of liver metastases. METHODS: Patient and
      tumor characteristics decisive for surgery of colorectal liver metastases were
      selected from literature. A factorial design was used to construct virtual
      patient cases by balanced combinations of these characteristics. Surgeons
      experienced in liver surgery (n=25) were asked to give their advised treatment
      (resection and/or local ablation, or chemotherapy). Different tumor and patient
      variables were weighted in the analysis for their contribution to treatment
      choices. RESULTS: Patient's age, the involvement of lobes and location of
      metastases in relation to large vessels were most important for treatment
      decisions. The number of metastases, size of the lesions, presence of resectable
      extrahepatic disease and time interval from primary tumor to metastases proved of
      less importance. Based on the analysis a computer-based decision model was
      designed. CONCLUSION: Conjoint analysis can be a valuable tool in clinical
      decision making. The computer-based decision model can assist clinicians in
      defining which patient should be referred for liver surgery.

PMID- 18053677
TI  - [Prevention of human papillomavirus (HPV)-induced infections: access of
      adolescent girls to health care. A population-based, cross-sectional
      observational study].
AB  - INTRODUCTION: The human papillomavirus (HPV) is the most common cause of sexually
      transmitted infections worldwide, and its prevalence is highest among young women
      aged 17-25 years. It is the principal risk factor for cervical cancer. Systematic
      vaccination of adolescent girls should significantly reduce the incidence of this
      disease and its related mortality. AIM: One of the objectives of the Enjeux
      study, a population-based survey, was to identify the place of young girls within
      the French health care system to help assess the optimal conditions for
      implementing anti-HPV vaccination. METHODS: Data came from 5354 interviews of
      women aged 18-70 years, 320 of whom provided information about daughters aged 11
      14 years and 406 about daughters aged 15-17 years. Among the latter, 318 were
      also interviewed and 294 completed a self-administered questionnaire. RESULTS:
      The results showed that sexual activity was reported by approximately one third
      of the girls aged 15-17 years. At-risk behaviors in these girls included
      insufficient contraception (only 51% use condoms). Data on the medical management
      of the population of 11-17 year-old girls indicate that they have access to - and
      are integrated into - the health care system, with frequent medical visits. They
      see the general practitioner (GP) most frequently, followed by the school doctor.
      The frequency of general practice visits is similar in both age groups; more than
      50% of the girls visit their GP more than twice a year. Vaccination is a frequent
      reason for these visits; gynecologic reasons are less frequent. CONCLUSION: The
      results of this survey underline the central place of the GP in the health
      management of young girls aged 11 to 17 years.

PMID- 18053678
TI  - [The August 2003 heat wave in France: effects on psychiatric disorders and
      suicidal behavior].
AB  - INTRODUCTION: The psychological consequences of a disaster are usually analyzed
      in terms of their immediate impact, but since September 11, 2001, several studies
      have examined its effects on suicidal behavior. The aim of our survey was to
      analyze the associations between psychiatric disorders in a population and the
      heat wave that hit France in August 2003, during which 14,000 more people died
      than in comparable periods. METHODS: We studied a population of patients seeking
      emergency psychiatric care at a general hospital in Paris. We compared the number
      of patients and their reasons for consultation between June and October in 2002
      and in 2003. We focused on suicidal behavior, depressive disorders, anxiety, and
      stress disorder, analyzing 1632 cases for these two periods. RESULTS: Suicidal
      behavior was significantly less prevalent during the heat wave than in 2002: only
      12.3% of the patients were diagnosed with suicidal behavior in 2003 compared with
      25% in 2002. At the same time, the percentage of patients admitted to the
      psychiatric department was substantially higher in 2003 than in 2002: 32.1% in
      2003 compared with 15.4% in 2002. DISCUSSION: These results show that the social
      cohesion induced by disasters can produce social support that can be important in
      suicidal behavior. Reinforcing it may be crucial to reinforce for suicide
      prevention.

PMID- 18053679
TI  - Role of the hemin-binding protein 35 (HBP35) of Porphyromonas gingivalis in
      coaggregation.
AB  - Hemin-binding protein 35 (HBP35) in Porphyromonas gingivalis is one of the outer
      membrane proteins and has been reported to be a non-fimbrial coaggregation
      factor. In this study, a P. gingivalis HBP35-deficient mutant (MD774) was
      constructed from wild-type strain FDC381 by insertion mutagenesis in order to
      provide a better understanding of this protein's role in coaggregation. The
      intact cells and vesicles in FDC381 were found to have strong aggregation
      activities with Gram-positive bacteria. But neither the vesicles nor the intact
      cells showed aggregation activity in MD774. In addition, MD774 reduced
      autoaggregation activity. Immunoblot analysis of MD774 showed the presence of a
      non-maturated 45-kDa fimbrillin protein. Electron microscopy showed that the
      MD774 had no long fimbriae on the cell surface. Arg- and Lys-gingipain activity
      in MD774 was significantly decreased, compared with FDC381. Real-time RT-PCR
      demonstrated a significant reduction in the expression of gingipain-associated
      genes rgpA, rgpB, and kgp. In conclusion, we suggest that the reduction in
      coaggregation was caused by the combined reduction of a variety of molecules,
      including HBP35, gingipains, and fimbriae. Our results suggest that the HBP35
      protein directly influences not only coaggregation as an adhesion molecule but
      also indirectly influences the expression of other coaggregation factors.

PMID- 18053680
TI  - Important aspects of end-of-life care among veterans: implications for
      measurement and quality improvement.
AB  - To identify aspects of end-of-life care in the U.S. Department of Veterans
      Affairs (VA) health care system that are not assessed by existing survey
      instruments and to identify issues that may be unique to veterans, telephone
      interviews using open-ended questions were conducted with family members of
      veterans who had received care from a VA facility in the last month of life.
      Responses were compared to validated end-of-life care assessment instruments in
      common use. The study took place in four VA medical centers and one family member
      per patient was invited to participate, selected from medical records using
      predefined eligibility criteria. These family members were asked to describe
      positive and negative aspects of the care the veteran received in the last month
      of life. Interview questions elicited perceptions of care both at VA sites and at
      non-VA sites. Family reports were coded and compared with items in five existing
      prospective and retrospective instruments that assess the quality of care that
      patients receive near the end of life. Interviews were completed with 66 family
      members and revealed 384 codes describing both positive and negative aspects of
      care during the last month of life. Almost half of these codes were not
      represented in any of the five reference instruments (n=174; 45%). These codes,
      some of which are unique to the veteran population, were grouped into eight
      categories: information about VA benefits (n=36; 55%), inpatient care (n=36;
      55%), access to care (n=33; 50%), transitions in care (n=32; 48%), care that the
      veteran received at the time of death (n=31; 47%), home care (n=26; 40%), health
      care facilities (n=12; 18%), and mistakes and complications (n=18; 27%). Although
      most of the reference instruments assessed some aspect of these categories, they
      did not fully capture the experiences described by our respondents. These data
      suggest that many aspects of veterans' end-of-life care that are important to
      their families are not assessed by existing survey instruments. VA efforts to
      evaluate end-of-life care for veterans should not only measure common aspects of
      care (e.g., pain management), but also examine performance in areas that are more
      specific to the veteran population.

PMID- 18053681
TI  - Expression profile of ErbB receptor's family in human alveolar type 2-like cell
      line A549 exposed to hexavalent chromium.
AB  - Occupational exposure to hexavalent chromium (Cr (VI)) compounds is associated
      with increased risk of pulmonary disease. In the present study we have
      investigated temporal expression of ErbB's receptors family in A549 cells after
      exposure to Cr (VI). Treatment with 10 microM or 300 microM of Na2CrO4 induced
      apoptotic cell death within 24h. Based on data obtained by ELISA cell death
      detection method and fluorescence microscopy, the concentration of 10 microM was
      chosen to study the expression of ErbB receptors family. Such concentration
      reflects a condition of acute toxicity in which cells survived up to 24h. Real
      time quantitative PCR has been performed to analyze the expression profiles of
      ErbB family genes following chromium toxicity. The expression of EGFR and ErbB2
      receptors was significantly reduced after 1h and 4h of treatment while ErbB2
      receptor was significantly increased and EGFR receptor returned to basal value
      after 24h. Instead, ErbB3 receptor was overexpressed after 1h, returned to basal
      level after 4h and increased its level after 24h. Exposure to chromium did not
      change expression level of ErbB4 receptor in A549 cell line. The present data
      suggests that expression changes in ErbB receptors might have a role in the
      carcinogenic effects induced by this pneumotoxic agent.

PMID- 18053682
TI  - Relationships between information processing, depression, fatigue and cognition
      in multiple sclerosis.
AB  - The neurobehavioral sequelae of multiple sclerosis (MS) consistently include
      fatigue, depression and cognitive dysfunction with slower processing figuring
      prominently. However, processing speed is often confounded with accuracy and the
      relative contributions of depressed mood and fatigue in influencing speed of
      processing are difficult to quantify. Therefore, there were three objectives in
      this study. First, compare processing speed in MS and healthy controls under
      conditions in which accuracy is not confounded with speed; second, determine the
      relationships between information processing speed and cognition; third,
      determine the contributions of clinical depression and fatigue in mediating these
      relationships. Forty-eight participants with confirmed MS participated. The
      findings suggested that slower processing was correlated with higher levels of
      depressed mood, fatigue, lower verbal fluency, fewer words and digits recalled
      and poorer recall of visual-spatial information. Depression and physical fatigue
      had the greatest influence on the association between processing speed and more
      effortful tasks (e.g., immediate word recall and word list learning). Current
      findings extend previous work by using a more sensitive measure of processing
      speed and by quantifying the relative contributions of depression and fatigue in
      mediating relationships between processing speed and cognition.

PMID- 18053683
TI  - Autism spectrum traits in children and adolescents with obsessive-compulsive
      disorder (OCD).
AB  - OBJECTIVE: Assess the prevalence of autistic traits (AST) in pediatric obsessive
      compulsive disorder (OCD) and relate them to OCD co-morbidity and compare them
      with published normative data. METHODS: Pediatric patients with obsessive
      compulsive disorder (n=109) according to the DSM-IV were studied using parent
      ratings of the Autistic Symptom/Syndrome Questionnaire to assess AST symptoms as
      a continuous rather than categorical trait. The KSADS, a semi-structured
      psychiatric interview, was used for the psychiatric diagnostic evaluation. Also,
      the Children's Yale-Brown Obsessive-Compulsive Scale was used to assess OCD
      severity and other clinical features. RESULTS: AST was common among our patients.
      Symptom scores were highest in cases with co-morbid Autistic Spectrum Disorders,
      but cases with other co-morbidities as tics/Tourette and attention/behavioral
      disorders also scored higher. All sub-groups, including OCD without these co
      morbidities scored higher than the Swedish normative group. Using ANOVA, co
      morbid ASD and tics/Tourette (plus a term for gender by tic interaction
      indicating that girls with tics scored high, otherwise low) and pathological
      doubt contributed (R2=.41) to the AST-traits, while OCD severity and co-morbid
      anxiety- and depressive disorders did not. CONCLUSION: AST traits are prevalent
      in OCD and seem to be intricately associated with the co-morbidities as well as
      the OCD syndrome itself. The findings might have implication for our nosological
      understanding of OCD which currently is discussed.

PMID- 18053684
TI  - Sex differences in the recognition of and innate antiviral responses to Seoul
      virus in Norway rats.
AB  - Among rodents that carry hantaviruses, more males are infected than females. Male
      rats also have elevated copies of Seoul virus RNA and reduced transcription of
      immune-related genes in the lungs than females. To further characterize sex
      differences in antiviral defenses and whether these differences are mediated by
      gonadal hormones, we examined viral RNA in the lungs, virus shedding in saliva,
      and antiviral defenses among male and female rats that were intact,
      gonadectomized neonatally, or gonadectomized in adulthood. Following inoculation
      with Seoul virus, high amounts viral RNA persisted longer in lungs from intact
      males than intact females. Removal of the gonads in males reduced the amount of
      viral RNA to levels comparable with intact females at 40 days post-inoculation
      (p.i.). Intact males shed more virus in saliva than intact females 15 days p.i.;
      removal of the gonads during either the neonatal period or in adulthood increased
      virus shedding in females and decreased virus shedding in males. Induction of
      pattern recognition receptors (PRRs; Tlr7 and Rig-I), expression of antiviral
      genes (Myd88, Visa, Jun, Irf7, Ifnbeta, Ifnar1, Jak2, Stat3, and Mx2), and
      production of Mx protein was elevated in the lungs of intact females compared
      with intact males. Gonadectomy had more robust effects on the induction of PRRs
      than on downstream IFNbeta or Mx2 expression. Putative androgen and estrogen
      response elements are present in the promoters of several of these antiviral
      genes, suggesting the propensity for sex steroids to directly affect dimorphic
      antiviral responses against Seoul virus infection.

PMID- 18053685
TI  - Retinol, carotenoids, and tocopherols in the milk of lactating adolescents and
      relationships with plasma concentrations.
AB  - OBJECTIVE: We determined the concentrations of retinol, carotenoids, and
      tocopherols in breast milk of adolescents and evaluated their associations with
      plasma levels and with maternal characteristics (period of lactation, body mass
      index, age of menarche, and years postmenarche). METHODS: This was a single cross
      sectional survey of retinol, carotenoid, and tocopherol composition of milk and
      plasma of lactating adolescent mothers (n = 72; 30-120 d postpartum) attending
      public daycare clinics in Rio de Janeiro, Brazil. Milk and plasma components were
      analyzed by high-performance liquid chromatography. RESULTS: Nutrient
      concentrations (micromoles per liter, mean +/- SE) in plasma and milk were,
      respectively, retinol 2.1 +/- 0.5 and 0.62 +/- 0.44, beta-carotene 0.18 +/- 0.19
      and 0.016 +/- 0.017, alpha-carotene 0.05 +/- 0.04 and 0.0035 +/- 0.002, lutein
      plus zeaxanthin 0.15 +/- 0.11 and 0.025 +/- 0.024, lycopene 0.1 +/- 0.11 and
      0.016 +/- 0.025, alpha-tocopherol 10.8 +/- 5.3 and 2.7 +/- 1.8, gamma-tocopherol
      2.6 +/- 2.3 and 0.37 +/- 0.15. The milk/plasma molar ratios of retinol and
      tocopherols were two times higher than those of carotenoids. Significant
      correlations (P < 0.001) between milk and plasma nutrient levels were observed
      for beta-carotene (r = 0.41), alpha-carotene (r = 0.60), and lutein plus
      zeaxanthin (r = 0.57), but not for lycopene, retinol, and tocopherols. Nutrient
      concentrations in plasma and in milk were not associated with the maternal
      characteristics investigated. CONCLUSION: Concentrations of the nutrients
      studied, especially retinol and alpha-tocopherol, in mature milk of lactating
      adolescents were, in general, lower than in milk of adult lactating women. Milk
      concentrations were associated with plasma concentrations only for beta-carotene,
      alpha-carotene, and lutein plus zeaxanthin.

PMID- 18053686
TI  - Neural bases for impaired social cognition in schizophrenia and autism spectrum
      disorders.
AB  - Schizophrenia and autism both feature significant impairments in social cognition
      and social functioning, but the specificity and mechanisms of these deficits
      remain unknown. Recent research suggests that social cognitive deficits in both
      disorders may arise from dysfunctions in the neural systems that underlie social
      cognition. We explored the neural activation of discrete brain regions implicated
      in social cognitive and face processing in schizophrenia subgroups and autism
      spectrum disorders during complex social judgments of faces. Twelve individuals
      with autism spectrum disorders (ASD), 12 paranoid individuals with schizophrenia
      (P-SCZ), 12 non-paranoid individuals with schizophrenia (NP-SCZ), and 12 non
      clinical healthy controls participated in this cross sectional study. Neural
      activation, as indexed by blood oxygenation level dependent (BOLD) contrast, was
      measured in a priori regions of interest while individuals rated faces for
      trustworthiness. All groups showed significant activation of a social cognitive
      network including the amygdala, fusiform face area (FFA), superior temporal
      sulcus (STS), and ventrolateral prefrontal cortex (VLPFC) while completing a task
      of complex social cognition (i.e. trustworthiness judgments). ASD and P-SCZ
      individuals showed significantly reduced neural activation in the right amygdala,
      FFA, and left VLPFC as compared to controls and in the left VLPFC as compared to
      NP-SCZ individuals during this task. These findings lend support to models
      hypothesizing well-defined neural substrates of social cognition and suggest a
      specific neural mechanism that may underlie social cognitive impairments in both
      autism and paranoid schizophrenia.

PMID- 18053688
TI  - General and social cognition in first episode schizophrenia: identification of
      separable factors and prediction of functional outcome using the IntegNeuro test
      battery.
AB  - OBJECTIVE: It is increasingly recognized that cognitive assessments, unlike
      symptom ratings, provide a reliable predictor of functional outcome in
      schizophrenia. This study evaluated the utility of the 'IntegNeuro' computerized
      test battery for assessing cognition in first episode schizophrenia. We
      determined the presence of separable factors of general and social cognition,
      their equivalence to the consensus domains identified by the NIMH MATRICS
      project, and their effectiveness in predicting real world functional outcomes.
      METHOD: Fifty six first episode schizophrenia (FES) patients and 112 matched
      healthy controls were assessed on the touchscreen-based 'IntegNeuro' cognitive
      test battery and FES patients for social functioning (SOFAS) and quality of life
      (WHOQOL-BREF). RESULTS: Principal components analysis identified i) six factors
      corresponding to MATRICS domains of general cognition ('Information Processing
      Speed', 'Verbal Recall', 'Working Memory Capacity', 'Sustained
      Attention/Vigilance', 'Verbal Processing', 'Executive Function'), ii) an
      'Emotional Intelligence' factor corresponding to the MATRICS social cognition
      domain, and iii) an additional 'Sensori-Motor Function' factor of general
      cognition and 'Negativity' factor of social cognition. Patients showed
      impairments relative to controls across all factors, but especially for Working
      Memory Capacity, followed by Verbal Memory, Sustained Attention/Vigilance and
      Negativity. These factors strongly predicted poorer social functioning in FES,
      along with poorer quality of life in psychological, social, and health
      satisfaction facets. CONCLUSION: The IntegNeuro battery has utility for assessing
      separable domains of general and social cognition in FES, which are predictive of
      real world outcomes. Thus, it may be appropriate for clinical application,
      including in multi-center trials targeting new treatments for cognition in
      schizophrenia.

PMID- 18053687
TI  - Age-associated differences in cognitive performance in older community dwelling
      schizophrenia patients: differential sensitivity of clinical neuropsychological
      and experimental information processing tests.
AB  - Cognitive dysfunction is a common feature of schizophrenia and deficits are
      present before the onset of psychosis, and are moderate to severe by the time of
      the first episode. Controversy exists over the course of cognitive dysfunction
      after the first episode. This study examined age-associated differences in
      performance on clinical neuropsychological (NP) and information processing tasks
      in a sample of geriatric community living schizophrenia patients (n=172).
      Compared to healthy control subjects (n=70), people with schizophrenia did not
      differ on NP tests across age groups but showed evidence for age-associated
      cognitive worsening on the more complex components of an information-processing
      test. Age-related changes in cognitive function in schizophrenia may be a
      function of both the course of illness and the processing demands of the
      cognitive measure of interest. Tests with fixed difficulty, such as clinical NP
      tests, may differ in their sensitivity from tests for which parametric difficulty
      manipulations can be performed.

PMID- 18053689
TI  - Weight gain induced by haloperidol, risperidone and olanzapine after 1 year:
      findings of a randomized clinical trial in a drug-naive population.
AB  - BACKGROUND: There is little information about weight gain induced by
      antipsychotics at long-term. OBJECTIVE: To quantify the weight gain induced by
      first (haloperidol) and second generation antipsychotics (olanzapine and
      risperidone) in a cohort of drug-naive subjects after 1 year of treatment.
      METHODS: This is a prospective, randomized clinical trial, including a
      representative sample of first episode psychotic incident cases from a population
      area of 555.000 people. The main outcome measures were changes in body weight and
      body mass index at 3 months and at 12 months. Both a per protocol analysis and an
      intention to treat analysis were conducted. RESULTS: A total of 164 drug-naive
      patients were included. At 12 months 144 patients were evaluated. Of them, 66%
      completed the protocol and 34% needed treatment switch. We found statistically
      significant differences in weight gain at 3 months: 3.8 kg (+/-4.1) for
      haloperidol, 5.9 kg (+/-5.1) for risperidone and 8.4 kg (+/-5.0) for olanzapine
      (F=7.045; p=0.002). After 1 year the difference in weight gain had disappeared:
      9.7 kg (+/-5.7) for haloperidol, 8.9 kg (+/-8.8) for risperidone and 10.9 kg (+/
      7.2) for olanzapine (F=0.817; p=0.445). CONCLUSIONS: Drug-naive patients
      experience an extraordinary weight gain after 1 year of treatment with
      haloperidol, olanzapine or risperidone. The main difference among these
      treatments is the pattern of weight gain but not the final amount of weight gain.

PMID- 18053690
TI  - C-terminal peptide of IGFBP-3, KGRKR, prolongs the proliferative potential of
      basal keratinocytes.

PMID- 18053691
TI  - Urosepsis: from the intensive care viewpoint.
AB  - A recent survey conducted by the Competence Network Sepsis (SepNet) revealed that
      severe sepsis and/or septic shock occurs in 75000 inhabitants (110 per 100,000)
      and sepsis occurs in 79000 inhabitants (116 per 100,000) in Germany annually. The
      prevalence of urosepsis in this survey was 7%. Early diagnosis of sepsis prior to
      the onset of clinical deterioration is of particular interest because this would
      increase the possibility of early and specific treatment, which in turn is the
      major determining factor of mortality in septic patients. Treatment of urosepsis
      consists of source control, early antimicrobial therapy as well as supportive and
      adjunctive therapy. For supportive therapy, adequate volume loading is the most
      important step in the treatment of patients with urosepsis in order to restore
      and maintain oxygen transport and tissue oxygenation. Therefore, supportive
      treatment should focus on adequate volume resuscitation and appropriate use of
      inotropes/vasopressors. The PROWESS study is the first investigation
      demonstrating the decrease in mortality in patients with sepsis following
      administration of activated protein C (APC). Thus, administration of APC to
      patients with two-organ failure or an APACHE II score > or =25 within the first
      24 h after the first sepsis-induced organ failure is a part of adjunctive
      therapy. Additionally, current data support low-dose hydrocortisone therapy in
      patients with vasopressor-dependent severe septic shock. Time to initiation of
      therapy is crucial for surviving sepsis. Implementing new medical evidence in
      this context into daily clinical intensive care remains a major hurdle.

PMID- 18053692
TI  - The ligand activity of AGE-proteins to scavenger receptors is dependent on their
      rate of modification by AGEs.
AB  - The cellular interaction of proteins modified with advanced glycation end
      products (AGEs) is believed to induce several different biological responses,
      which are involved in the development of diabetic vascular complications. We
      report here that the ratio of protein glycation is implicated in its ligand
      activity to scavenger receptors. Although highly-modified AGE-bovine serum
      albumin (high-AGE-BSA) was significantly recognized by human monocyte-derived
      macrophages and Chinese hamster ovary cells which overexpress such scavenger
      receptors as CD36, SR-BI (scavenger receptor class B type-I), and LOX-1 (Lectin
      like Ox-LDL receptor-1), the mildly-modified-AGE-BSA (mild-AGE-BSA) did not show
      any ligand activity to these cells. Furthermore, when (111)In-labeled high- or
      mild-AGE-BSA were injected into the tail vein of mice, the high-AGE-BSA was
      rapidly cleared from the circulation whereas the clearance rate of the mild-AGE
      BSA was very slow, similar to the native BSA. These results demonstrate the first
      evidence that the ligand activity of the AGE-proteins to the scavenger receptors
      and its pharmacokinetic properties depend on their rate of modification by AGEs,
      and we should carefully prepare the AGE-proteins in vitro to clarify the
      physiological significance of the interaction between the AGE-receptors and AGE
      proteins.

PMID- 18053693
TI  - Microtubule anchoring by cortical actin bundles prevents streaming of the oocyte
      cytoplasm.
AB  - The localisation of the determinants of the body axis during Drosophila oogenesis
      is dependent on the microtubule (MT) cytoskeleton. Mutations in the actin binding
      proteins Profilin, Cappuccino (Capu) and Spire result in premature streaming of
      the cytoplasm and a reorganisation of the oocyte MT network. As a consequence,
      the localisation of axis determinants is abolished in these mutants. It is
      unclear how actin regulates the organisation of the MTs, or what the spatial
      relationship between these two cytoskeletal elements is. Here, we report a
      careful analysis of the oocyte cytoskeleton. We identify thick actin bundles at
      the oocyte cortex, in which the minus ends of the MTs are embedded. Disruption of
      these bundles results in cortical release of the MT minus ends, and premature
      onset of cytoplasmic streaming. Thus, our data indicate that the actin bundles
      anchor the MTs minus ends at the oocyte cortex, and thereby prevent streaming of
      the cytoplasm. We further show that actin bundle formation requires Profilin but
      not Capu and Spire. Thus, our results support a model in which Profilin acts in
      actin bundle nucleation, while Capu and Spire link the bundles to MTs. Finally,
      our data indicate how cytoplasmic streaming contributes to the reorganisation of
      the MT cytoskeleton. We show that the release of the MT minus ends from the
      cortex occurs independently of streaming, while the formation of MT bundles is
      streaming dependent.

PMID- 18053694
TI  - Lola regulates cell fate by antagonizing Notch induction in the Drosophila eye.
AB  - Lola is a transcription repressor that regulates axon guidance in the developing
      embryonic nervous system of Drosophila. Here, we show that Lola regulates two
      binary cell fate decisions guided by Notch inductive signaling in the developing
      eye: the R3-R4 and the R7-cone cell fate choices. Lola is required cell
      autonomously in R3 for its specification, and Lola transforms R4 into R3 if
      overexpressed. Lola also promotes R7 fate at the expense of cone cell fate. Lola
      antagonizes Notch-dependent gene expression and Notch-dependent fate
      transformation. Expression analysis shows that Lola is constitutively present in
      all photoreceptors and cone cells. We propose that when a precursor cell receives
      a weak Notch inductive signal, it is not sufficiently strong to overcome the
      constitutive repression of target gene transcription by Lola. A precursor that
      receives a strong Notch inductive signal expresses target genes despite a
      constitutive repression by Lola. The predicted consequence of this mechanism is
      to sharpen a cell's responsiveness to Notch signaling by creating a threshold.

PMID- 18053695
TI  - Long-term regular exercise promotes memory and learning in young but not in older
      rats.
AB  - BACKGROUND AND OBJECTIVE: By aging, some functions in nervous system like spatial
      memory are reduced. It has been shown that short-time physical activity can
      improve memory but there is much less data on the long-term exercising. In the
      present study, the aim was to clarify the effect of regular long-term physical
      activity on spatial memory and learning of young and middle aged and older male
      Wistar rats. MATERIALS AND METHODS: Sixty 3 months old rats were randomly divided
      in six equal groups. Experimental groups were treadmill exercised at speed
      22m/min for 1h 6 days per week, and the program lasted 3, 6 and 9 months,
      respectively. At the end of training period, spatial memory of rats was tested
      using Morris Water Maze. RESULTS: Results indicated that regular physical
      activity significantly increased spatial memory (p<0.05) in young rats (6 months
      old) as compared to controls, but not in the older ones (9 and 12 months old).
      Nonetheless, spatial memory of these rats was significantly better than in
      younger ones in both groups (p<0.05). CONCLUSION: Spatial memory and learning
      increased due regular exercise in young rats. With progression of age up to 9 and
      12 months the memory improved, but the programmed exercise had no positive effect
      on learning.

PMID- 18053696
TI  - A de-identifier for medical discharge summaries.
AB  - OBJECTIVE: Clinical records contain significant medical information that can be
      useful to researchers in various disciplines. However, these records also contain
      personal health information (PHI) whose presence limits the use of the records
      outside of hospitals. The goal of de-identification is to remove all PHI from
      clinical records. This is a challenging task because many records contain foreign
      and misspelled PHI; they also contain PHI that are ambiguous with non-PHI. These
      complications are compounded by the linguistic characteristics of clinical
      records. For example, medical discharge summaries, which are studied in this
      paper, are characterized by fragmented, incomplete utterances and domain-specific
      language; they cannot be fully processed by tools designed for lay language.
      METHODS AND RESULTS: In this paper, we show that we can de-identify medical
      discharge summaries using a de-identifier, Stat De-id, based on support vector
      machines and local context (F-measure=97% on PHI). Our representation of local
      context aids de-identification even when PHI include out-of-vocabulary words and
      even when PHI are ambiguous with non-PHI within the same corpus. Comparison of
      Stat De-id with a rule-based approach shows that local context contributes more
      to de-identification than dictionaries combined with hand-tailored heuristics (F
      measure=85%). Comparison with two well-known named entity recognition (NER)
      systems, SNoW (F-measure=94%) and IdentiFinder (F-measure=36%), on five
      representative corpora show that when the language of documents is fragmented, a
      system with a relatively thorough representation of local context can be a more
      effective de-identifier than systems that combine (relatively simpler) local
      context with global context. Comparison with a Conditional Random Field De
      identifier (CRFD), which utilizes global context in addition to the local context
      of Stat De-id, confirms this finding (F-measure=88%) and establishes that
      strengthening the representation of local context may be more beneficial for de
      identification than complementing local with global context.

PMID- 18053697
TI  - Subcoating with Kollidon VA 64 as water barrier in a new combined native
      dextran/HPMC-cetyl alcohol controlled release tablet.
AB  - A novel oral controlled delivery system for propranolol hydrochloride (PPL) was
      developed and optimized using wet granulation process. We are studying the
      ability of subcoating with Kollidon VA 64 as a barrier to water penetration in
      matrix cores combined hydrophilic (native dextran-HPMC)/hydrophobic (cetyl
      alcohol) prior to film coating with Opradry II-YS-30-18056. The copovidone (i.e.,
      Kollidon VA 64) not only increases the mechanical properties of tablets (less
      friability) but also reduces the amount of absorbed water from the air in
      tropical stability condition (25 degrees C and 75% relative humidity). The in
      vitro dissolution profiles of coated sustained-release matrix tablets of racemic
      PPL were determined and compared with uncoated tablet cores according to the
      United States Pharmacopeia (USP) Tolerance Specifications for Propranolol
      Hydrochloride Extended-Release Capsules. A comparative kinetic study of the
      present matrix tablets (coated and uncoated cores) and commercial SUMIAL RETARD
      capsules (reference formulation (R) (Spain) was established). The values for the
      similarity factor (f2=61.756, f2=72.326 and f2=88.509 for initial time, one year
      and two years, respectively (uncoated cores vs. capsule) and f2=63.904, f2=69.502
      and f2=76.348 (coated tablets vs. capsule) for initial time, one year and 2 two
      years, respectively) suggested that the dissolution profiles of the present three
      sustained-release oral dosage forms are similar and stable during two years under
      stability condition.

PMID- 18053700
TI  - Crop residues as soil amendments and feedstock for bioethanol production.
AB  - Traditional solid fuels account for more than 90% of the energy supply for 3
      billion people in developing countries. However, liquid biofuels (e.g., ethanol)
      are perceived as an important alternative to fossil fuel. Global crop residue
      production is estimated at about 4 billion Mg for all crops and 3 billion Mg per
      annum for lignocellulosic residues of cereals. One Mg of corn stover can produce
      280L of ethanol, compared with 400L from 1Mg of corn grains; 1Mg of biomass is
      also equivalent to 18.5GJ of energy. Thus, 3 billion Mg of residues are
      equivalent to 840 billion L of ethanol or 56x10(9)GJ of energy. However, removal
      of crop residues exacerbates soil degradation, increases net emission of CO2, and
      aggravates food insecurity. Increasing the SOC pool by 1 Mg C ha(-1)yr(-1)
      through residue retention on soil can increase world food grain production by 24
      40 million Mg yr(-1), and root/tuber production by 6-11 million Mg yr(-1). Thus,
      identifying alternate sources of biofuel feedstock (e.g., biofuel plantations,
      animal waste, municipal sold waste) is a high priority. Establishing biofuel
      plantations on agriculturally marginal or degraded lands can off-set 3.5-4 Pg
      Cyr(-1).

PMID- 18053699
TI  - Mechanisms to control rereplication and implications for cancer.
AB  - Recent advances in the replication field have highlighted how the replication
      initiator proteins are negatively regulated by inhibitor proteins and ubiquitin
      mediated degradation in mammalian cells to prevent rereplication. When these
      regulatory pathways go awry, uncontrolled rereplication ensues and a G2/M
      checkpoint is evoked to prevent cellular death. Many components of the
      checkpoints activated by rereplicaton are important for cancer prevention by
      facilitating DNA damage repair processes. The pathways that prevent rereplication
      themselves have also recently been implicated in preventing tumorigenesis.
      Studies from patient tumors, genetically altered mice, and mammalian cell culture
      suggest that deregulation of replication licensing proteins results in an
      increase in aneuploidy, chromosomal fusions, and DNA breaks. These studies
      provide a framework to address how regulators of replication function to maintain
      genomic stability.

PMID- 18053701
TI  - Carbon--making the right choice for waste management in developing countries.
AB  - Due to initiatives such as the clean development mechanism (CDM), reducing
      greenhouse gas emissions for a developing country can offer an important route to
      attracting investment in a variety of qualifying project areas, including waste
      management. To date CDM projects have been largely confined to schemes that
      control emission from landfill, but projects that avoid landfilling are beginning
      to be submitted. In considering the waste options which might be suitable for
      developing countries certain ones, such as energy from waste, have been
      discounted for a range of reasons related primarily to the lack of technical and
      other support services required for these more sophisticated process trains. The
      paper focuses on six options: the base case of open dumping; three options for
      landfill (passive venting, gas capture with flaring, and gas capture with energy
      production), composting and anaerobic digestion with electricity production and
      composting of the digestate. A range of assumptions were necessary for making the
      comparisons based on the effective carbon emissions, and these assumptions will
      change from project to project. The highest impact in terms of carbon emissions
      was from using a sanitary landfill without either gas flaring or electricity
      production; this was worse than the baseline case using open dumpsites. Landfills
      with either flaring or energy production from the collected gas both produced
      similar positive carbon emissions, but these were substantially lower than both
      open dumping and sanitary landfill without flaring or energy production.
      Composting or anaerobic digestion with energy production and composting of the
      digestate were the two best options with composting being neutral in terms of
      carbon emissions and anaerobic digestion being carbon negative. These generic
      conclusions were tested for sensitivity by modifying the input waste composition
      and were found to be robust, suggesting that subject to local study to confirm
      assumptions made, the opportunity for developing CDM projects to attract
      investment to improved waste management infrastructure is significant. Kyoto
      credits in excess of 1 tCO2e/t of waste could be realised.

PMID- 18053702
TI  - Soils, climate change and the OECD.
AB  - Some concepts of sustainability applied to soils are given in relation to the
      Organisation for Economic Co-operation and Development (OECD) Co-operative
      Research Programme 'Biological Resource Management for Sustainable Agricultural
      Systems'. The application of these concepts to climate change will be discussed
      in relation to seven high-profile papers published over the past 12 months. It is
      argued that multi-disciplinary (including social science) approaches are needed
      to address the issues. There is also a brief discussion on biomass energy in
      terms of soil sustainability and climate change.

PMID- 18053703
TI  - Control of GHG emission at the microbial community level.
AB  - All organic material eventually is decomposed by microorganisms, and considerable
      amounts of C and N end up as gaseous metabolites. The emissions of greenhouse
      relevant gases like carbon dioxide, methane and nitrous oxides largely depend on
      physico-chemical conditions like substrate quality or the redox potential of the
      habitat. Manipulating these conditions has a great potential for reducing
      greenhouse gas emissions. Such options are known from farm and waste management,
      as well as from wastewater treatment. In this paper examples are given how
      greenhouse gas production might be reduced by regulating microbial processes.
      Biogas production from manure, organic wastes, and landfills are given as
      examples how methanisation may be used to save fossil fuel. Methane oxidation, on
      the other hand, might alleviate the problem of methane already produced, or the
      conversion of aerobic wastewater treatment to anaerobic nitrogen elimination
      through the anaerobic ammonium oxidation process might reduce N2O release to the
      atmosphere. Changing the diet of ruminants, altering soil water potentials or a
      change of waste collection systems are other measures that affect microbial
      activities and that might contribute to a reduction of carbon dioxide equivalents
      being emitted to the atmosphere.

PMID- 18053704
TI  - Microarray-based expression profiling and informatics.
AB  - Microarray-based expression profiling is a powerful technology for studying
      biological mechanisms and for developing clinically valuable predictive
      classifiers. The high-dimensional read-out for each sample assayed makes it
      possible to do new kinds of studies but also increases the risks of misleading
      conclusions. We review here the current state-of-the-art for design and analysis
      of microarray-based investigations.

PMID- 18053705
TI  - Tissue microarrays: emerging standard for biomarker validation.
AB  - With the widespread use of DNA microarrays, hundreds of biomarkers are in need of
      validation in cohorts of well-annotated clinical samples. Tissue microarrays are
      emerging as the tool par excellence to rapidly perform DNA, RNA, and especially
      protein expression analyses on large numbers of clinical samples. Although still
      somewhat limited by the subjectivity of scoring methods and tissue sample
      representativeness, TMAs represent an increasingly validated means of
      understanding the clinical impact of diagnostic-related, prognostic-related, and
      therapy-related markers. Automated methods are being developed for TMA analysis
      and cell microarrays and frozen tissue TMAs have been better optimized. More and
      more biomarker studies are availing themselves of the high-throughput nature of
      TMAs, recognizing that they are becoming indispensable for rapid translation of
      laboratory data to the clinic.

PMID- 18053707
TI  - A Greenwood formula for standard error of the age-standardised relative survival
      ratio.
AB  - The age-standardised relative survival ratio is used to compare population-based
      cancer survival patterns when the population age structures differ.
      Traditionally, the direct standardisation method based on age-specific relative
      survival ratios has been used. In a new method [Brenner H, Arndt V, Gefeller O,
      Hakulinen T. An alternative approach to age adjustment of cancer survival rates.
      Eur J Cancer 2004;40:2317-22], weighted observations depending on the age
      structures of the study and standard populations are used to substitute the
      patients leading to a use of weighted counts. The relative survival ratio is then
      calculated in the conventional way. However, no standard error of the age
      standardised relative survival estimate has been reported. In this paper, we
      introduce a generalisation of the well-known Greenwood formula for that purpose.
      This method is also applicable for the observed survival and particularly when
      the observed survival probabilities of the patient population differ by age
      stratum. The traditional Greenwood formula is a special case of the method when
      no specific weights are used and the observed survival probability is the same in
      each stratum. Data from the Finnish Cancer Registry are used for illustration.

PMID- 18053708
TI  - An approach for prediction of optimum reaction conditions for laccase-catalyzed
      bio-transformation of 1-naphthol by response surface methodology (RSM).
AB  - Response surface methodology (RSM) was successfully applied to enzymatic bio
      transformation of 1-naphthol. The experiments were conducted in a closed system
      containing acetone and sodium acetate buffer, with laccase enzyme. Laccase enzyme
      used as catalyst was derived from Trametes versicolor (ATCC 200801). The
      enzymatic bio-transformation rate of 1-naphthol, based on measurements of initial
      dissolved oxygen (DO) consumption rate in the closed system, was optimized by the
      application of RSM. The independent variables, which had been found as the most
      effective variables on the initial DO consumption rate by screening experiments,
      were determined as medium temperature, pH and acetone content. A quadratic model
      was developed through RSM in terms of related independent variables to describe
      the DO consumption rate as the response. Based on contour plots and variance
      analysis, optimum operational conditions for maximizing initial DO consumption
      rate, while keeping acetone content at its minimum value, were 301 K of
      temperature, pH 6 and acetone content of 7% to obtain 9.17 x 10(-3) mM DO/min for
      initial oxidation rate.

PMID- 18053706
TI  - Xeroderma pigmentosum complementation group C genotypes/diplotypes play no
      independent or interaction role with polycyclic aromatic hydrocarbons-DNA adducts
      for breast cancer risk.
AB  - Xeroderma pigmentosum complementation group C (XPC) is an important DNA nuclear
      excision repair (NER) gene that recognises the damage caused by a variety of
      bulky DNA adducts. We evaluated the association of two common non-synonymous
      polymorphisms in XPC (Ala499Val and Lys939Gln) with breast cancer risk in the
      Long Island Breast Cancer Study Project (LIBCSP), a population-based case-control
      study. Genotyping of 1067 cases and 1110 controls was performed by a high
      throughput assay with fluorescence polarisation. There were no overall
      associations between XPC polymorphisms and breast cancer risk. A diplotype CC-CC
      was significantly associated with increased breast cancer risk compared with
      diplotype CA-CA (OR=1.4, 95%CI: 1.0-1.9), but was not significant when compared
      with all other diplotypes combined (OR=1.22, 95%CI: 0.97-1.53). No modification
      effects were observed for XPC genotypes by cigarette smoking status, smoking pack
      years or polycyclic aromatic hydrocarbons (PAH)-DNA adducts. The increase in
      breast cancer risk was slightly more pronounced among women with detectable PAH
      DNA adducts and carrying the diplotype CC-CC (OR=1.6, 95%CI: 1.1-2.2) compared to
      women with non-detectable PAH-DNA adducts carrying other diplotypes combined, but
      no statistically significant interaction was observed (P(interaction)=0.69).
      These data suggest that XPCs have neither independent effects nor interactions
      with cigarette smoking and PAH-DNA adducts for breast cancer risk. Further
      studies with multiple genetic polymorphisms in NER pathway are warranted.

PMID- 18053709
TI  - Polyhydroxyalkanoate production from whey by Pseudomonas hydrogenovora.
AB  - Whey permeate from dairy industry was hydrolyzed enzymatically to cleave its main
      carbon source, lactose, to glucose and galactose. The hydrolysis products were
      chosen as carbon sources for the production of poly-3-hydroxybutyric acid (PHB)
      by Pseudomonas hydrogenovora. In shaking flask experiments, the utilization of
      whey permeate as a cheap substrate was compared to the utilization of pure
      glucose and galactose for bacterial growth under balanced conditions as well as
      for the production of PHB under nitrogen limitation. After determination of the
      inhibition constant Ki for sodium valerate on biomass production (Ki=1.84 g/l),
      the biosynthesis of PHA co-polyesters containing 3-hydroxybutyrate (3HB) and 3
      hydroxyvalerate (3HV) units from hydrolyzed whey permeate and valerate was
      investigated. The application of hydrolyzed whey permeate turned out to be
      advantageous compared with the utilization of pure sugars. Therefore,
      fermentation under controlled conditions in a bioreactor was performed with
      hydrolyzed whey permeate to obtain detailed kinetic data (maximum specific growth
      rate, mu max=0.291/h, maximum polymer concentration, 1.27 g/l PHB), values for
      molecular mass distribution (weight average molecular weight Mw=353.5 kDa,
      polydispersity index PDI=3.8) and thermo analytical data. The fermentation was
      repeated with co-feeding of valerate (maximum specific growth rate,
      mu(max)=0.201/h, maximum polymer concentration, 1.44 g/l poly-(3HB-co-21%-3HV),
      weight average molecular weight M(w)=299.2 kDa, polydispersity index PDI=4.3).

PMID- 18053710
TI  - Conceptual schematic for capture of biomethane released from hydroelectric power
      facilities.
AB  - Though dam-related biomethane was identified in the 1960s, its capture has not
      been sufficiently discussed. Captured biomethane could be burned to produce
      energy, and the burning of biomethane turns the carbon in it into CO(2) that is
      far less potent as a greenhouse gas; this paper therefore aims to technically
      discuss the capture/use of dam-related biomethane. A great amount of bubbles
      would be formed by the rapid drop in water pressure (i.e. cavitation) after
      turbine passage, so it is proposed to capture methane-bearing bubbles by means of
      a flow tube for adjusting residence time and hydrophilic screens for trapping
      these bubbles. The results from the performed calculation show that biomethane
      can be trapped in a yield of 60%.

PMID- 18053711
TI  - Biosorption of copper by marine algae Gelidium and algal composite material in a
      packed bed column.
AB  - Marine algae Gelidium and algal composite material were investigated for the
      continuous removal of Cu(II) from aqueous solution in a packed bed column. The
      biosorption behaviour was studied during one sorption-desorption cycle of Cu(II)
      in the flow through column fed with 50 and 25 mg l(-1) of Cu(II) in aqueous
      solution, at pH 5.3, leading to a maximum uptake capacity of approximately 13 and
      3 mg g(-1), respectively, for algae Gelidium and composite material. The
      breakthrough time decreases as the inlet copper concentration increases, for the
      same flow rate. The pH of the effluent decreases over the breakthrough time of
      copper ions, which indicates that ion exchange is one of the mechanisms involved
      in the biosorption process. Temperature has little influence on the metal uptake
      capacity and the increase of the ionic strength reduces the sorption capacity,
      decreasing the breakthrough time. Desorption using 0.1M HNO(3) solution was 100%
      effective. After two consecutive sorption-desorption cycles no changes in the
      uptake capacity of the composite material were observed. A mass transfer model
      including film and intraparticle resistances, and the equilibrium relationship,
      for adsorption and desorption, was successfully applied for the simulation of the
      biosorption column performance.

PMID- 18053712
TI  - An efficient, simple and expedition synthesis of 1-amidoalkyl-2-naphthols as
      'drug like' molecules for biological screening.
AB  - An efficient and direct protocol for the preparation of amidoalkyl naphthols
      employing a multi-component, one-pot condensation reaction of beta-naphthol,
      aromatic aldehydes and acetamide in the presence of ferric hydrogensulfate under
      solvent, solvent-free and microwave conditions is described. The thermal solvent
      free and microwave green procedures offer advantages such as shorter reaction
      times, simple work-up, excellent yield, recovery and reusability of catalyst. It
      is noteworthy that 1-amidomethyl-2-naphthols can be converted into important
      biological 'drug like' active 1-aminomethyl-2-naphthols derivatives by amide
      hydrolysis.

PMID- 18053713
TI  - Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective
      5-HT6 receptor antagonists.
AB  - A 5,7-dichloro-3-phenyl-3-methyl-quinoline-2,4-dione (11a) has been identified in
      a random screen as a lead for 5-HT(6) antagonist. During the lead optimization
      process, several analogs were synthesized and their biological activities were
      investigated. Within this series, several compounds display high binding affinity
      and selectivity for the 5-HT(6) receptor. In particular, 3-(4-hydroxyphenyl)-3
      methyl-quinoline-2,4-dione (12f) exhibits high affinity (K(i)=12.3 nM) for 5
      HT(6) receptor with good selectivity over other serotonin and dopamine (D(1)
      D(4)) receptor subtypes. In a functional adenylyl cyclase stimulation assay, this
      compound exhibited considerable antagonistic activity (IC(50)=0.61 microM).

PMID- 18053714
TI  - Structure and property based design of factor Xa inhibitors: biaryl pyrrolidin-2
      ones incorporating basic heterocyclic motifs.
AB  - Structure and property based drug design was exploited in the synthesis of
      sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating basic
      biaryl P4 groups, producing highly potent inhibitors with significant
      anticoagulant activities and encouraging oral pharmacokinetic profiles.

PMID- 18053715
TI  - Antimicrobial activities of the bromophenols from the red alga Odonthalia
      corymbifera and some synthetic derivatives.
AB  - A series of bromophenols was obtained by isolation from red alga Odonthalia
      corymbifera and by reactions of bis(hydroxyphenyl)methanes with bromine. New
      bromophenols including 3,3',5,5'-tetrabromo-2,2',4,4'-tetrahydroxydiphenylmethane
      (10), a regioisomer of the potent antimicrobial natural product, together with
      known derivatives were synthesized in high yield. All of the isolated and
      synthesized compounds were tested for antimicrobial activity against gram
      negative, gram-positive bacteria and fungi. The preliminary structure-activity
      relationship, to elucidate the essential structure requirements for antimicrobial
      activity, has been described. Among the isolated natural products 2,2',3,3'
      tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane (4) was found to be the most
      active derivative against Candida albicans, Aspergillus fumigatus, Trichophyton
      rubrum, and Trichophyton mentagrophytes. The synthetic bromophenols 3,3'-dibromo
      6,6'-dihydroxydiphenylmethane (13) and 3,3',5,5'-tetrabromo-6,6'
      dihydroxydiphenylmethane (14) showed potent antibacterial effect against
      Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Proteus vulgaris,
      and Salmonella typhimurium.

PMID- 18053716
TI  - Ohioensins F and G: protein tyrosine phosphatase 1B inhibitory
      benzonaphthoxanthenones from the Antarctic moss Polytrichastrum alpinum.
AB  - Ohioensins F and G (1 and 2), two new benzonaphthoxanthenones, have been isolated
      from the MeOH extract of Antarctic moss Polytrichastrum alpinum by various
      chromatographic methods. The structures of these compounds were determined mainly
      by analysis of NMR spectroscopic data. The known compounds ohioensins A and C (3
      and 4) were also obtained. Compounds 1-4 showed potent inhibitory activity
      against therapeutically targeted protein tyrosine phosphatase 1B (PTP1B). Kinetic
      analysis of PTP1B inhibition by ohioensin F (1) suggested that
      benzonaphthoxanthenones inhibited PTP1B activity in a non-competitive manner.

PMID- 18053717
TI  - 2-Substituted 4-, 5-, and 6-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]pyridazin-3(2H)
      ones and 2-substituted 4,5-bis[(1E)-3-oxo-3-phenylprop-1-en-1-yl]pyridazin-3(2H)
      ones as potent platelet aggregation inhibitors: design, synthesis, and SAR
      studies.
AB  - A set of regioisomeric 2-substituted pyridazin-3(2H)-ones containing a 3-oxo-3
      phenylprop-1-en-1-yl fragment at either position 4, 5 or 6 and 2-substituted
      pyridazin-3(2H)-ones containing the same fragment both at positions 4 and 5 have
      been synthesized and evaluated as antiplatelet agents. The study allows the
      identification of a new highly potent platelet aggregation inhibitor (4c).

PMID- 18053718
TI  - LAMA2 mRNA processing alterations generate a complete deficiency of laminin
      alpha2 protein and a severe congenital muscular dystrophy.
AB  - An increasing number of genomic variations are no more regarded as harmless
      changes in protein coding sequences or as genetic polymorphisms. Studying the
      impact of these variations on mRNA metabolism became a central issue to better
      understand the biological significance of disease. We describe here a severe
      congenital muscular dystrophy (CMD) with lumbar scoliosis and respiratory
      complications in a patient, who died at the age of 10. Despite a poor linkage to
      any form of CMD, total deficiency of laminin-alpha2 rather suggested the
      occurrence of an MDC1A form. Extensive analysis of LAMA2 gene revealed two novel
      mutations: a (8007delT) frameshift deletion in exon 57, and a de novo 7nt
      deletion in intron 17. Using an ex vivo approach, we provided strong evidence
      that the intron mutation is responsible for complete exon 17 skipping. The
      mutations are in trans and they each generate a nonsense mRNA potentially
      elicited to degradation by NMD. We further discuss the impact of mRNA alterations
      on the subtle phenotypic discrepancies.

PMID- 18053719
TI  - Dropped head syndrome as prominent clinical feature in MuSK-positive Myasthenia
      Gravis with thymus hyperplasia.
AB  - MuSK-positive Myasthenia Gravis is in most cases clinically characterized by a
      progressive course with severe oculobulbar involvement or prominent neck,
      shoulder and respiratory muscle weakness. It is also distinguished from other
      forms of myastehnia through its lack of germinal centers or lymphocytic
      infiltrates in the thymic tissue. We present the case of a MuSK-positive female
      myasthenic patient with over four years slowly progressive weakness of the neck
      extensor muscles in the presence of thymus hyperplasia and discuss its uncommon
      and markedly focal clinical and electrophysiological features, as well as the
      excellent course under medication with pyridostigmine and prednisone, especially
      after thymectomy.

PMID- 18053720
TI  - Preimplantation genetic diagnosis for myotonic dystrophy type 1 in the UK.
AB  - Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder caused by
      expansion of a trinucleotide repeat in a non-coding region of DMPK. Prenatal
      diagnosis (PND) is available; however, the decision to terminate affected
      pregnancies is difficult as the extent of disability is hard to predict from the
      size of the expansion. In preimplantation genetic diagnosis (PGD) genetic
      analysis is carried out before the establishment of pregnancy. This paper reviews
      the largest number of cycles of PGD for DM1 in the UK indicating that PGD is a
      practical option for affected couples.

PMID- 18053722
TI  - Prolonged standing as a precursor for the development of low back discomfort: an
      investigation of possible mechanisms.
AB  - Low back discomfort (LBD) has been associated with prolonged periods of standing,
      yet research has shown that the magnitude of spinal loading during standing is
      relatively minimal. Therefore, the mechanism of this discomfort is not fully
      understood. Research has monitored numerous variables during prolonged periods of
      standing; however the focus of this work has been primarily on the comparison of
      the effect of different floor surfaces on these variables. No study to date has
      made an attempt to relate these changes to the development of LBD. The purpose of
      this study was therefore to determine possible mechanisms for the development of
      LBD during standing by monitoring biological variables. It was hypothesized that
      during a prolonged standing period, LBD would develop and the measured variables
      would change over time. Sixteen individuals stood for 2h while activation of
      torso and hip muscles, lumbar spine posture, back extensor muscle oxygenation,
      torso skin temperature, and centre of pressure changes under the feet were
      monitored over time. Thirteen out of sixteen individuals developed LBD as a
      result of the prolonged standing period, which significantly increased over the 2
      h period (p<0.0001). Only three of the 37 variables measured were significantly
      altered over time. However, a generated regression model incorporating 15 of the
      16 individuals (which incorporated how each individual stood in the first 15 min)
      explained 78% of the variance in LBD at the end of the 2-h standing period.
      Prolonged standing resulted in LBD, yet few significant changes in the measured
      variables were observed over time. It is possible that LBD is not linked with
      alterations in standing over time, but rather associated with how an individual
      initially stands.

PMID- 18053721
TI  - Is breast cancer incidence increasing among young women? An analysis of the trend
      in France for the period 1983-2002.
AB  - The purpose of the study was to describe the trend in the incidence of breast
      cancer in women under 40 in France for the period 1983-2002 and compare it with
      the trend observed in other age groups. Data from seven cancer registries were
      analysed. Annual percentage changes were estimated in different age groups using
      Poisson regression. During the period 1983-2002, breast cancer incidence in women
      under 40 increased regularly, with an estimated annual percentage change of 0.65
      (95% CI: 0.03-1.26). In women aged over 40, the increase is more significant,
      particularly among women aged 50-74 (2.93% per year). The increase in breast
      cancer incidence in women under 40 was low and steady over the 20-year period
      considered. Even though young women did not experience such a major change in
      diagnostic practices as the development of screening among women aged 50-74, it
      is difficult to distinguish the effects of possible changes in risk factors and
      in diagnostic practices in the slight increase observed.

PMID- 18053723
TI  - Lateral epicondylar femoral avulsion fracture combined with tibial fracture: a
      counterpart to the arcuate sign.
AB  - We present a case of femoral avulsion of the lateral collateral ligament (LCL)
      with complete tear of the posterior cruciate ligament (PCL) and popliteus tendon
      accompanied by demonstrable posterolateral rotary instability (PLRI) of the knee.
      A 55-year-old man was involved in a road traffic accident. Radiographs revealed
      an avulsion fracture of the lateral epicondyle of the femur and a fracture of the
      tibial shaft. An MRI scan showed the lateral epicondyle was avulsed by the LCL
      and the popliteus tendon. The PCL signal was absent. The tibial shaft fracture
      was fixed with an intra medullary nail. Sagging of the tibia, with loss of
      prominence of tibial tuberosity and a positive posterior drawer test,
      demonstrated a complete tear of the PCL. The avulsion fracture of the lateral
      epicondyle was treated by an open reduction and internal fixation with two
      staples. A ligament can be avulsed at either end, and to our knowledge, this
      pattern of injury as a counterpart to arcuate sign has never been documented in
      the literature. It is important not to dismiss a small avulsion fracture around
      the knee joint as insignificant, as it could indicate the presence of a major
      ligamentous injury.

PMID- 18053724
TI  - Bilateral functional popliteal artery entrapment in a young athlete.
AB  - Popliteal artery entrapment syndrome is a frequent cause of intermittent
      claudication in young patients. We present a case of a bilateral functional
      entrapment, where static imaging did not demonstrate the occlusion until the
      patient's feet were placed in forced plantar flexion. A high index of clinical
      suspicion and dynamic tests with provocative manoeuvres are needed to diagnose
      this condition.

PMID- 18053725
TI  - Recurrence of varus/valgus deformity after TKR at 3 years' follow-up.
AB  - We assessed 30 patients with a cemented TKR implant (Interax ISA, Stryker
      Orthopaedics) at 1 and 3 years follow-up. We wanted to ascertain whether knee
      alignment was maintained during the critical period of follow-up in meniscal
      bearing PCL-retaining TKR patients and test if correlations exist between
      alignment variations in the coronal plane and preoperative varus/valgus deformity
      or tibial component position and migration with respect to the tibia. Lower limb
      alignment was evaluated by measuring the angle between the tibia and femur
      anatomical axis directly from the antero-posterior radiographs and the tibial
      component position with respect to the tibial anatomical axis. The tibial
      component varus/valgus migration in the tibia was measured by roentgen
      stereophotogrammetric analysis. The results showed that at 3 years follow-up 40%
      of patients presented an alignment variation of over 3 degrees . The recurrent
      deformity was not correlated with the preoperative deformity, nor with the tibial
      component position with respect to the tibial shaft nor with its migration. After
      total knee arthroplasty coronal axial variation is a common finding and it
      depends on the overall limb muscles and ligaments adaptation to prosthetic
      constraints.

PMID- 18053726
TI  - Inhibitors of proteases and amide hydrolases that employ an alpha-ketoheterocycle
      as a key enabling functionality.
AB  - This article reviews the scientific literature on the application of alpha
      ketoheterocycles to the discovery of potent enzyme inhibitors. The alpha
      ketoheterocycle functionality provides a moderately electrophilic ketone carbonyl
      with 'tunable' reactivity, as well as a structural template for introducing new
      interactions in the enzyme active-site cleft. This type of moiety has served an
      important role in the design of active-site-directed inhibitors of diverse serine
      and cysteine proteases, and of fatty acid amide hydrolase (FAAH). Potent
      inhibitors have been identified for, inter alia, elastase, thrombin, factor Xa,
      tryptase, chymase, cathepsin K, cathepsin S, and FAAH. For example, 6e is an
      orally active inhibitor of human neutrophil elastase that entered human clinical
      studies, 52h is an orally bioavailable inhibitor of human chymase, and 82m is a
      FAAH inhibitor with in vivo endocannabinoid-enhancing activity.

PMID- 18053727
TI  - Novel anti-HIV cyclotriazadisulfonamide derivatives as modeled by ligand- and
      receptor-based approaches.
AB  - Computer-aided prediction of new anti-HIV compounds, derived from substructures
      of 2-amino-6-arylsulfonylbenzonitriles and cyclotriazadisulfonamide analogues,
      has been reported. A ligand-based approach, namely MIA-QSAR, and a docking
      evaluation were used to model the title compounds, macrocycles containing a
      trisubstituted benzene moiety. According to the MIA-QSAR method, predicted
      potencies for proposed compounds were up to seven times higher than that of the
      experimentally most active compound of training set. Moreover, we have used
      docking approaches to study the binding orientations and predict binding
      affinities of these compounds in CD4 receptor.

PMID- 18053728
TI  - Trypanocidal activity of a new pterocarpan and other secondary metabolites of
      plants from Northeastern Brazil flora.
AB  - Two hundred fifteen compounds isolated from plants of Northeastern Brazil flora
      have been assayed against epimastigote forms of Trypanosoma cruzi, using the
      tetrazolium salt MTT as an alternative method. Eight compounds belonging to four
      different species: Harpalyce brasiliana (Fabaceae), Acnistus arborescens and
      Physalis angulata (Solanaceae), and Cordia globosa (Boraginaceae) showed
      significant activity. Among them, a novel and a known pterocarpan, a chalcone,
      four withasteroids, and a meroterpene benzoquinone were the represented chemical
      classes.

PMID- 18053729
TI  - Synthesis of (nor)tropeine (di)esters and allosteric modulation of glycine
      receptor binding.
AB  - (Hetero)aromatic mono- and diesters of tropine and nortropine were prepared.
      Modulation of [3H]strychnine binding to glycine receptors of rat spinal cord was
      examined with a ternary allosteric model. The esters displaced [3H]strychnine
      binding with nano- or micromolar potencies and strong negative cooperativity.
      Coplanarity and distance of the ester moieties of diesters affected the binding
      affinity being nanomolar for isophthaloyl-bistropane and nortropeines.
      Nortropisetron had the highest affinity (K(A) approximately 10 nM). Two esters
      displayed negative cooperativity with glycine in displacement, while three esters
      of low-affinity and nortropisetron exerted positive cooperativity with glycine.

PMID- 18053730
TI  - Sulfonamide-1,2,4-triazole derivatives as antifungal and antibacterial agents:
      synthesis, biological evaluation, lipophilicity, and conformational studies.
AB  - A series of 10 new 5-[2-(substituted sulfamoyl)-4,5-dimethoxy-benzyl]-4aryl-s
      triazole-3-thiones were synthesized and evaluated for in vitro antifungal and
      antibacterial activity. All compounds tested showed significant antifungal
      activity against all the micromycetes, compared to the commercial fungicide
      bifonazole. Differences in their activity depend on the substitution of different
      reactive groups. More specifically, best antifungal activity among synthetic
      analogues was shown with N-dimethylsulfamoyl group. All the compounds tested
      against bacteria showed the same activity as the commercial agent streptomycin,
      except for Enterobacter cloacce and Salmonella species. Chloramphenicol showed
      lower bactericidal effect than the synthetic compounds. Furthermore, it is
      apparent that different compounds reacted in different ways against bacteria.
      Gram (-) bacteria seem to be more sensitive to these compounds than Gram (+)
      species. An effort was made to correlate the above-mentioned differences in
      activity with lipophilicity studies. Furthermore, molecular modeling was used to
      obtain the main conformational features of this class of molecules for future
      structure-activity relationship studies.

PMID- 18053731
TI  - Oxazaborolidine derivatives inducing autoinducer-2 signal transduction in Vibrio
      harveyi.
AB  - The bioluminescence of the marine bacterium Vibrio harveyi is controlled by
      quorum sensing. This effect is mediated by production, accumulation, and auto
      detection of the species-specific autoinducer 1 (AI-1), autoinducer 2 (AI-2), and
      the V. cholerae autoinducer 1 (CAI-1). The V. harveyi AI-2 was recently
      identified as furanosyl borate diester. We synthesized several oxazaborolidine
      derivatives that chemically resemble the structure of AI-2. Five oxazaborolidine
      derivatives (BNO-1 to BNO-5) were tested, however only BNO-1 (3,4-dimethyl-2,5
      diphenyl-1,3,2-oxazaborolidine), and BNO-5 (2-butyl-3,4-dimethyl-5-phenyl-1,3,2
      oxazaborolidine) strongly induced V. harveyi bioluminescence in V. harveyi mutant
      (BB170) lacking sensor 1. A dose-dependent relationship between those
      oxazaborolidine derivatives and bioluminescence induction was observed with this
      V. harveyi strain (BB170). BNO-1 and BNO-5 did not affect V. harveyi BB886
      lacking sensor 2. Using a mutant strain which produces neither AI-1 nor AI-2 (V.
      harveyi MM77) we showed that the presence of spent medium containing AI-2 is
      essential for BNO-1 and BNO-5 activity. This effect was similar when introducing
      the spent medium and the BNOs together or at a 3-h interval. A comparable
      induction of bioluminescence was observed when using synthetic DPD (pre-AI-2) in
      the presence of BNO-1 or BNO-5. The mode of action of BNO-1 and BNO-5 on
      bioluminescence of V. harveyi is of a co-agonist category. BNO-1 and BNO-5
      enhanced AI-2 signal transduction only in the presence of AI-2 and only via
      sensor 2 cascade. BNO-1 and BNO-5 are the first oxazaborolidines reported to
      affect AI-2 activity. Those derivatives represent a new class of borates which
      may become prototypes of novel agonists of quorum sensing mediated by AI-2 in V.
      harveyi.

PMID- 18053732
TI  - The synthesis of bivalent 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)-8
      heterobicyclo[3.2.1]octanes as probes for proximal binding sites on the dopamine
      and serotonin transporters.
AB  - 3-Aryltropanes have been widely explored for potential medications for
      remediation of cocaine abuse. Research has focused predominantly on 8-azatropanes
      and it is now well recognized that these compounds can be designed to manifest
      varied selectivity and potency for inhibition of the dopamine, serotonin, and
      norepinephrine uptake systems. We had reported that the 8-nitrogen atom present
      in the 3-aryltropanes is not essential for tropanes to bind to monoamine uptake
      systems. We demonstrated that compounds in which the amine had been exchanged for
      an ether or a thioether retained binding potency and selectivity. We have now
      designed bivalent compounds in which two tropane moieties are linked by an
      intervening chain. These 8-homo- and 8-heterotropane bivalent compounds allowed a
      search for adjacent tropane binding sites on the DAT as well as a further
      exploration of whether the binding sites for 8-azatropanes are the same as those
      for other 8-heterotropanes. A comparison of these compounds with their progenitor
      tropanes cast into doubt the existence of proximal binding sites on the DAT, and
      offered support for the existence of different binding sites for the 8
      azatropanes compared with 8-oxa- and 8-thiatropanes. Indeed, 8-aza bivalent
      tropanes inhibited DAT with potency about 10-fold lower (DAT: IC50 = 31 nM) than
      their monovalent counterparts. Furthermore, bivalent ligands in which one or both
      of the tropanes was devoid of an amine suffered a further loss of inhibitory
      potency. We conclude that it is unlikely that there exist two tropane binding
      sites in close proximity to one another on either the DAT or SERT.

PMID- 18053733
TI  - Synthesis of 2-(1,1-dicyanopropen-2-yl)-6-(2-[18F]-fluoroethyl)-methylamino
      naphthalene ([18F]FDDNP).
AB  - 2-(1,1-dicyanopropen-2-yl)-6-(2-[18F]-fluoroethyl)-methylamino-naphthalene
      ([18F]FDDNP) was synthesized in a single step labeling procedure. The precursor,
      2-(1,1-dicyanopropen-2-yl)-6-(2-tosyloxyoethyl)-methylamino-naphthalene, was
      fluorinated with 18F in acetonitrile. After 15 min the reaction mixture was
      subjected to preparative HPLC purification. The product was isolated from the
      HPLC eluent with solid-phase extraction, and formulated in an ascorbic acid
      solution to prevent formation of side products during formulation. Quantitative
      sticking to tubing and filters was overcome by the addition of polysorbatum-80.
      This formulation yielded an isotonic, pyrogen-free and sterile solution of
      [18F]FDDNP. The overall decay-corrected radiochemical yield was 41+/-11% (n=22).
      Radiochemical purity was >98% and the specific activity was 102+/-56 GBq/micromol
      at the end of synthesis.

PMID- 18053734
TI  - Expression and functional analysis of aspartate transcarbamoylase and role of de
      novo pyrimidine synthesis in regulation of growth and development in Arabidopsis.
AB  - Aspartate transcarbamoylase (ATCase, EC 2.1.3.2) catalyzes the committed step in
      the de novo synthesis of uridine-5'-monophosphate (UMP), from which all other
      pyrimidine nucleotides are made. In Arabidopsis, ATCase is encoded by a single
      PYRB gene, whose expression was regulated by tissue pyrimidine availability. RT
      PCR and PYRB:GUS expression profiles showed markedly increased expression of PYRB
      in root tissues during the first 5days after germination, as seed pyrimidine
      reserves were exhausted and de novo synthesis was required to support new growth.
      Growth of seedlings in the presence of the ATCase inhibitor N-(phosphonacetyl)-l
      aspartate (PALA) resulted in complete developmental arrest at the day 5 stage,
      which was reversible upon addition of exogenous uracil. Arabidopsis RNAi lines
      exhibiting 70-95% reductions in PYRB transcript and ATCase protein levels had
      delayed growth and development, produced smaller plants with reduced root to
      shoot biomass ratios, few flowers, and siliques that produced smaller seeds with
      greatly reduced viability, compared with wild type plants. The severity of the
      phenotype was correlated with the extent of PYRB silencing and was reversible by
      pyrimidine addition. These results suggest that de novo synthesis is required,
      although minimal activities, supplemented by efficient salvaging pathway
      activities, are able to meet metabolic demands for pyrimdines during growth and
      development. Coordinate changes in expression of salvage and catabolic pathway
      genes in RNAi plants indicate that pyrimidine metabolism responds dynamically to
      changes in tissue pyrimidine availability.

PMID- 18053735
TI  - Response of the photosynthetic apparatus of cotton (Gossypium hirsutum) to the
      onset of drought stress under field conditions studied by gas-exchange analysis
      and chlorophyll fluorescence imaging.
AB  - The functioning of the photosynthetic apparatus of cotton (Gossypium hirsutum)
      grown during the onset of water limitation was studied by gas-exchange and
      chlorophyll fluorescence to better understand the adaptation mechanisms of the
      photosynthetic apparatus to drought conditions. For this, cotton was grown in the
      field in Central Asia under well-irrigated and moderately drought-stressed
      conditions. The light and CO(2) responses of photosynthesis (A(G)), stomatal
      conductance (g(s)) and various chlorophyll fluorescence parameters were
      determined simultaneously. Furthermore, chlorophyll fluorescence images were
      taken from leaves to study the spatial pattern of photosystem II (PSII)
      efficiency and non-photochemical quenching parameters. Under low and moderate
      light intensity, the onset of drought stress caused an increase in the operating
      quantum efficiency of PSII photochemistry (varphi(PSII)) which indicated
      increased photorespiration since photosynthesis was hardly affected by water
      limitation. The increase in varphi(PSII) was caused by an increase of the
      efficiency of open PSII reaction centers (F(v)'/F(m)') and by a decrease of the
      basal non-photochemical quenching (varphi(NO)). Using a chlorophyll fluorescence
      imaging system a low spatial heterogeneity of varphi(PSII) was revealed under
      both irrigation treatments. The increased rate of photorespiration in plants
      during the onset of drought stress can be seen as an acclimation process to avoid
      an over-excitation of PSII under more severe drought conditions.

PMID- 18053736
TI  - Plants, MEN and SIN.
AB  - In fission yeast, the onset of septation is signalled through the septum
      initiation network (SIN) signaling pathway. Similarly, in budding yeast the onset
      of budding is signalled through the mitotic exit network (MEN) pathway. We
      previously characterized in Arabidopsis signaling elements (GTPases, kinases)
      closely related to the core elements (spg1p/TEM1p, cdc7p/CDC15p) of the SIN and
      MEN pathways. Our first results suggested that a plant signaling pathway must be
      used to coordinate mitotic exit with cytokinesis. This review questioned the
      value of such an hypothesis in a multicellular organism. The core elements (G
      protein, kinase) of the SIN and MEN pathways were only detected in fungi, plants
      and Mycetozoa. We also noticed that AtSGP GTPase and AtMAP3Kepsilon kinase
      revealed two paralogues in Arabidopsis. Although Arabidopsis genes complement
      fission yeast mutants, and Arabidopsis proteins interact with fission yeast
      proteins, plants do not use these core elements to coordinate the termination of
      cell division with cytokinesis. Transcriptional regulation and expression data
      suggest a function for the plant SIN-like elements in the control of cell type
      specification. Exploring the evolutionary conservation of an ancient signaling
      pathway provides evidence that evolution has recycled regulatory elements for
      elaborating a new signaling avenue.

PMID- 18053737
TI  - The role of video assisted thoracoscopic pleurectomy/decortication in the
      therapeutic management of malignant pleural mesothelioma.
AB  - OBJECTIVE: Extrapleural pneumonectomy (EPP) has high mortality and morbidity;
      radical pleurectomy decortication (P/D) carries less mortality but still
      significant morbidity. This surgery is not suitable for many patients with
      malignant pleural mesothelioma (MPM) for whom video assisted thoracic surgery
      (VATS) offers a minimally invasive alternative. We aimed to assess the role of
      VATS decortication for MPM. METHODS: Over a 9-year period 208 patients underwent
      therapeutic surgery for MPM in our unit. One hundred and twelve of the patients
      underwent EPP, 29 had a P/D and 67 had VATS decortication. Sixty-three of the 208
      patients (EPP n=13, P/D n=8 and VATS decortication n=42) were 65 years of age or
      older at the time of the operation (57 males and 6 females, age 70 (65-80)
      years). In this group we analyzed perioperative morbidity and mortality and long
      term survival data using the Kaplan-Meier method. RESULTS: Postoperative stay and
      30-day mortality was significantly lower for VATS P/D than for EPP (14.3 days vs
      36.6 days, p<0.05 and mortality 7.1% vs 23%, respectively). There was no
      significant difference in the overall mean survival between the two groups (11.5
      months for EPP and 14 months for VATS P/D, p=0.6). CONCLUSION: VATS decortication
      should be considered in the therapeutic strategy for MPM.

PMID- 18053738
TI  - Endogenous IL-10 leads to impaired bacterial clearance and reduced survival in a
      murine model of chronic peritonitis.
AB  - We previously observed insufficient neutrophil accumulation and a lack of TNF
      alpha response at the site of infection until bacteria numbers >10(5) colony
      forming units in our model of chronic murine peritonitis, suggesting a defective
      host response after bacterial challenge with Klebsiella pneumoniae (Klebsiella).
      The aim of this study was to determine a potentially immunosuppressive effect of
      IL-10 in this model of chronic peritonitis. Balb/c animals were injected with
      10(3) colony forming units Klebsiella intraperitoneally. Gentamicin (5 mg/kg/day
      BID) was given subcutaneously (s.c.) for two days and then withdrawn. Animals
      were treated with anti-IL-10 antibody or IgG isotype control (s.c.) before or
      after Klebsiella administration. Survival was determined over 14 days. Similarly
      treated animals were harvested after 48 h to obtain liver tissue, peritoneal
      fluid and blood. Bacteria and neutrophil counts were determined. TNF-alpha and IL
      10 were measured by ELISA. Anti-IL-10 antibody significantly increased survival
      and bacterial clearance in the observed compartments. Anti-IL-10 administration
      did not lead to an increase in TNF-alpha concentrations or neutrophil
      accumulation at the site of infection at lower levels of Klebsiella. We conclude
      that endogenous IL-10 is detrimental for survival and bacterial clearance in this
      model of chronic peritonitis.

PMID- 18053740
TI  - Production and comprehensive quality control of recombinant human Interleukin
      1beta: a case study for a process development strategy.
AB  - We describe an efficient strategy to produce high-quality proteins by using a
      single large IMAC chromatography column and enzymatic His-tag removal via the
      TAGZyme system in pilot scale. Numerous quality assays demonstrated a high purity
      of the final product, the human cytokine Interleukin-1beta (IL-1beta). The
      protein preparation was apparently free of host cell proteins, endotoxins,
      protease, and aggregates. The N-terminal amino acid sequence of IL-1beta was in
      full agreement with the natural mature form of IL-1beta. The homogeneity of the
      product was further shown by X-ray structure determination which confirmed the
      previously solved structure of the protein. We propose the applied workflow as a
      strategy for industrial production of protein-based biopharmaceuticals.

PMID- 18053739
TI  - Transcriptional regulation of Th17 cell differentiation.
AB  - The paradigm of effector T helper cell differentiation into either Th1 or Th2
      lineages has been profoundly shaken by the discovery of T cells that secrete IL
      17 and other inflammatory cytokines. This subset, referred to as Th17, is
      centrally involved in autoimmune disease and is important in host defense at
      mucosal surfaces. In mouse, a series of cytokines, including IL-6, IL-21, IL-23,
      and TGF-beta, function sequentially or synergistically to induce the Th17
      lineage. Other cytokines, including IL-2, IL-4, IFNgamma, and IL-27, inhibit
      differentiation of this lineage. Here we review how the nuclear orphan receptor
      RORgammat functions to coordinate the diverse cytokine-induced signals and thus
      controls Th17 cell differentiation.

PMID- 18053741
TI  - Role of the virulence plasmid pR99 and the metalloprotease Vvp in resistance of
      Vibrio vulnificus serovar E to eel innate immunity.
AB  - Vibrio vulnificus biotype 2 serovar E (VSE) is a bacterial pathogen that produces
      a haemorrhagic septicaemia called vibriosis in eels. Its ability to grow in blood
      is conferred by a recently described virulence plasmid [Lee CT, Amaro C, Wu KM,
      Valiente E, Chang YF, Tsai SF, et al. A common virulence plasmid in biotype 2
      Vibrio vulnificus and its dissemination aided by a conjugal plasmid. Journal of
      Bacteriology, submitted for publication.]. In this study, we analyzed the role of
      this plasmid together with the role played by the metalloprotease (Vvp) in the
      interaction between bacteria and eel innate immunity. To this end, we compared
      and statistically analyzed the differences in resistance to serum and mucus
      factors (complement, selected antimicrobial peptides, transferrin and lysozyme)
      and also to phagocytosis/opsonophagocytosis between one VSE strain and its
      derivatives: a plasmid-cured strain and a vvp-deficient mutant. The wild-type and
      the metalloprotease-deficient strains were resistant to both the bactericidal
      action of fresh serum and the phagocytosis and opsonophagocytosis by eel
      phagocytes, confirming that Vvp is not involved in resistance to eel innate
      immunity. In contrast, the cured strain was sensitive to both the bactericidal
      action of eel serum activated by the alternative pathway and
      phagocytosis/opsonophagocytosis. Since no plasmid-encoded ORF, with homology to
      known genes, is related to the resistance to innate immunity [Lee CT, Amaro C, Wu
      KM, Valiente E, Chang YF, Tsai SF, et al. A common virulence plasmid in biotype 2
      Vibrio vulnificus and its dissemination aided by a conjugal plasmid. Journal of
      Bacteriology, submitted for publication.], this function could be codified by one
      or more new genes. Further studies are underway to characterize the plasmid
      encoded system responsible for V. vulnificus resistance to the innate immune
      system of eels.

PMID- 18053742
TI  - Tibialis posterior EMG activity during barefoot walking in people with neutral
      foot posture.
AB  - The aim of this study was to characterize the electromyographic (EMG) profile of
      tibialis posterior during barefoot walking in order to establish a reference
      database for neutral foot posture. Fifteen participants had their foot posture
      screened using the six-item Foot Posture Index. Bipolar intramuscular electrodes
      were inserted into tibialis posterior and peroneus longus utilizing ultrasound
      guidance. Surface electrodes were placed over medial gastrocnemius, peroneus
      brevis and tibialis anterior. EMG and footswitch gait characteristics were
      recorded whilst participants completed 10 barefoot walking trials. Individual and
      grand ensemble averages were used to characterize the intensity profiles for each
      muscle. Results indicated that for most of the participants, tibialis posterior
      displayed two bursts of EMG activity, with the first burst during the initial
      contact phase and the second burst during midstance. However, there was
      significant variability between participants. The grand ensemble average for
      tibialis posterior was comparable to peroneus longus which displayed similar
      temporal and intensity characteristics. It is suggested that this may reflect a
      synergistic relationship between these muscles during stance phase, although this
      was not consistent for all participants. Further research is required to
      determine if this relationship is altered in abnormal foot posture and whether it
      is clinically important. In conclusion, the EMG profile of tibialis posterior
      during the gait cycle appeared to be highly variable among participants. However,
      the authors believe that EMG findings from the participants with neutral foot
      posture in this study may be used for comparison to EMG patterns in people with
      abnormal foot posture and individuals affected by musculoskeletal disease.

PMID- 18053743
TI  - Older adults employ alternative strategies to operate within their maximum
      capabilities when ascending stairs.
AB  - Older people may operate much closer to their maximum capabilities than young
      adults when ascending stairs due to their lower maximum musculoskeletal
      capabilities. The purpose of this study was to establish the joint moment and
      range of motion demands of stair ascent relative to maximum capabilities in
      elderly and young adults. Fifteen elderly (mean age 75 years) and 17 young adult
      (mean age 25 years) participants ascended a purpose-built 4-step staircase with
      force platforms embedded into the steps and kinematic data was acquired using
      motion capture. Maximum musculoskeletal capabilities were assessed using a
      dynamometer. This study showed for the first time that stair ascent approaches
      the joint moment limits at the ankle in both young and older participants (
      approximately 90%). One of the most important and novel findings of this study
      was that elderly people were only capable of meeting the high demands by adopting
      a number of alternative strategies not observed in young adults: (i) applying the
      joint moments differently than young adults across the knee and ankle, (ii)
      translocating energy from the knee to the ankle, thereby enhancing the ankle
      joint moment upon maximum demand and (iii) by enabling the plantarflexors to act
      over a more favourable portion of the moment-angle relation upon maximum ankle
      joint moment demand. The elderly displayed a more cautious strategy to optimize
      positional stability during stair ascent, by maintaining a smaller separation
      between the centre of mass and centre of pressure in the frontal plane. It seems
      that elderly people may meet the demands of unaided stair ascent by adopting a
      number of alternative strategies to compensate for their reduced musculoskeletal
      capabilities.

PMID- 18053744
TI  - Language experience shapes early electrophysiological responses to visual
      stimuli: the effects of writing system, stimulus length, and presentation
      duration.
AB  - How language experience affects visual word recognition has been a topic of
      intense interest. Using event-related potentials (ERPs), the present study
      compared the early electrophysiological responses (i.e., N1) to familiar and
      unfamiliar writings under different conditions. Thirteen native Chinese speakers
      (with English as their second language) were recruited to passively view four
      types of scripts: Chinese (familiar logographic writings), English (familiar
      alphabetic writings), Korean Hangul (unfamiliar logographic writings), and
      Tibetan (unfamiliar alphabetic writings). Stimuli also differed in lexicality
      (words vs. non-words, for familiar writings only), length (characters/letters vs.
      words), and presentation duration (100 ms vs. 750 ms). We found no significant
      differences between words and non-words, and the effect of language experience
      (familiar vs. unfamiliar) was significantly modulated by stimulus length and
      writing system, and to a less degree, by presentation duration. That is, the
      language experience effect (i.e., a stronger N1 response to familiar writings
      than to unfamiliar writings) was significant only for alphabetic letters, but not
      for alphabetic and logographic words. The difference between Chinese characters
      and unfamiliar logographic characters was significant under the condition of
      short presentation duration, but not under the condition of long presentation
      duration. Long stimuli elicited a stronger N1 response than did short stimuli,
      but this effect was significantly attenuated for familiar writings. These results
      suggest that N1 response might not reliably differentiate familiar and unfamiliar
      writings. More importantly, our results suggest that N1 is modulated by visual,
      linguistic, and task factors, which has important implications for the visual
      expertise hypothesis.

PMID- 18053745
TI  - Hemispheric asymmetries in eye-hand coordination.
AB  - Manual asymmetries in limb kinematics and eye-hand coordination have usually been
      attributed to differences in online processing capabilities between the left and
      the right cerebral hemisphere. In the present fMRI experiment, we examined in
      right handers the brain areas involved in eye-hand coordination with either the
      left or the right hand. Although temporal and spatial accuracy was equal for left
      and right-hand movements, manual asymmetries were found in behavioral and
      neurophysiologic data, suggesting an asymmetric mode of control for left vs.
      right eye-hand coordination. For left eye-hand coordination, peak velocity and
      saccade completion occurred earlier than for the contralateral movements,
      suggesting that there was more time needed for homing-in on the target. When
      using the right hand, there was more activation in occipital areas. This might
      indicate a more intense visual processing or visualization of the target
      locations. When using the left hand, there was more activation in sensorimotor
      areas, frontal areas and cerebellum. This might point toward more processing
      effort. Left-hand movements may be considered as more difficult than right-hand
      movements by right-handed participants. Alternatively and more likely, these
      findings might reflect a difference in attention or resources attributed to
      different aspects of the tasks because of the different functional
      specializations of both hand/hemisphere systems.

PMID- 18053746
TI  - Model-free characterization of brain functional networks for motor sequence
      learning using fMRI.
AB  - Neuroimaging experiments have identified several brain regions that appear to
      play roles in motor learning. Here we apply a novel multivariate analytical
      approach to explore the dynamic interactions of brain activation regions as
      spatio-temporally coherent functional networks. We acquired BOLD fMRI signal
      during explicit motor sequence learning task to characterize the adaptive
      functional changes in the early phase of motor learning. Subjects practiced a 10
      digit, visually cued, fixed motor sequence during 15 consecutive 30 s practice
      blocks interleaved with similarly cued random sequence blocks. Tensor Independent
      Component Analysis (TICA) decomposed the data into statistically independent
      spatio-temporal processes. Two components were identified that represented task
      related activations. The first component showed decreasing activity of a fronto
      parieto-cerebellar network during task conditions. The other exclusively related
      to sequence learning blocks showed activation in a network including the
      posterior parietal and premotor cortices. Variation in expression of this
      component across individual subjects correlated with differences in behavior.
      Relative deactivations also were found in patterns similar to those described
      previously as "resting state" networks. Some of these deactivation components
      also showed task- and time-related modulations and were related to the behavioral
      improvement. The spatio-temporal coherence within these networks suggests that
      their elements are functionally integrated. Their anatomical plausibility and
      correlation with behavioral measures also suggest that this approach allows
      characterization of the interactions of functional networks relevant to the task.
      Particular value for multi-variant, model-free methods such as TICA lies in the
      potential for generating hypotheses regarding functional anatomical networks
      underlying specific behaviors.

PMID- 18053748
TI  - Proposing a manuscript peer-review checklist.
AB  - BACKGROUND: In the Internet-able era, reviewers are faced with an increased
      number of manuscripts and decreased time to review. In order to maintain the
      same, if not higher level of quality in the peer-review process, a net gain in
      productivity is required. Our goal is to present a manuscript peer-review
      checklist to help reviewers achieve this secondary yet critical task in a more
      systematic fashion. METHODS: To this end, we have compiled, structured and
      processed information from six reference standards and guidelines as well as
      directives from 21 peer-reviewed journals and conferences, resulting in a 71
      criteria checklist. We ensured that criteria were assessable based on the
      verification, validation and evaluation paradigm. RESULTS: The checklist is
      presented in the manuscript, along with a description of a review workflow.
      FINDINGS: It is hoped that the checklist will be widely disseminated, and we are
      looking for feedback on validation and improvements in order to perform a
      quantitative study on productivity gains using this tool.

PMID- 18053747
TI  - Spatial patterns of brain atrophy in MCI patients, identified via high
      dimensional pattern classification, predict subsequent cognitive decline.
AB  - Spatial patterns of brain atrophy in mild cognitive impairment (MCI) and
      Alzheimer's disease (AD) were measured via methods of computational neuroanatomy.
      These patterns were spatially complex and involved many brain regions. In
      addition to the hippocampus and the medial temporal lobe gray matter, a number of
      other regions displayed significant atrophy, including orbitofrontal and medial
      prefrontal grey matter, cingulate (mainly posterior), insula, uncus, and temporal
      lobe white matter. Approximately 2/3 of the MCI group presented patterns of
      atrophy that overlapped with AD, whereas the remaining 1/3 overlapped with
      cognitively normal individuals, thereby indicating that some, but not all, MCI
      patients have significant and extensive brain atrophy in this cohort of MCI
      patients. Importantly, the group with AD-like patterns presented much higher rate
      of MMSE decline in follow-up visits; conversely, pattern classification provided
      relatively high classification accuracy (87%) of the individuals that presented
      relatively higher MMSE decline within a year from baseline. High-dimensional
      pattern classification, a nonlinear multivariate analysis, provided measures of
      structural abnormality that can potentially be useful for individual patient
      classification, as well as for predicting progression and examining multivariate
      relationships in group analyses.

PMID- 18053749
TI  - Molecular systematics of South American dolphins Sotalia: sister taxa
      determination and phylogenetic relationships, with insights into a multi-locus
      phylogeny of the Delphinidae.
AB  - The evolutionary relationships among members of the cetacean family Delphinidae,
      the dolphins, pilot whales and killer whales, are still not well understood. The
      genus Sotalia (coastal and riverine South American dolphins) is currently
      considered a member of the Stenoninae subfamily, along with the genera Steno
      (rough toothed dolphin) and Sousa (humpbacked dolphin). In recent years, a
      revision of this classification was proposed based on phylogenetic analysis of
      the mitochondrial gene cytochrome b, wherein Sousa was included in the
      Delphininae subfamily, keeping only Steno and Sotalia as members of the
      Stenoninae subfamily. Here we investigate the phylogenetic placement of Sotalia
      using two mitochondrial genes, six autosomal introns and four Y chromosome
      introns, providing a total of 5,196 base pairs (bp) for each taxon in the
      combined dataset. Sequences from these genomic regions were obtained for 17
      delphinid species, including at least one species from each of five or six
      currently recognized subfamilies plus five odontocete outgroup species. Maximum
      Parsimony, Maximum Likelihood and Bayesian phylogenetic analysis of independent
      (each fragment) and combined datasets (mtDNA, nuDNA or mtDNA+nuDNA) showed that
      Sotalia and Sousa fall within a clade containing other members of Delphininae,
      exclusive of Steno. Sousa was resolved as the sister taxon to Sotalia according
      to analysis of the nuDNA dataset but not analysis of the mtDNA or combined
      mtDNA+nuDNA datasets. Based on the results from our multi-locus analysis, we
      offer several novel changes to the classification of Delphinidae, some of which
      are supported by previous morphological and molecular studies.

PMID- 18053750
TI  - Multigenic phylogeographic divergence in the paleoendemic southern Appalachian
      opilionid Fumontana deprehendor Shear (Opiliones, Laniatores, Triaenonychidae).
AB  - The paleoendemic opilionid Fumontana deprehendor is restricted to a small area of
      mid-elevation forested habitats in the southern Blue Ridge province of the
      Appalachian Mountains. In a recent study we reported on the discovery of 22 new
      montane populations of this monotypic genus, specimens from which exhibit
      remarkably little morphological divergence despite their separation by
      intervening lowlands and large riverine barriers. Here, we further explore
      spatial and temporal patterns of divergence in this taxon using DNA sequence data
      from a portion of the mitochondrial cytochrome c oxidase subunit I gene (
      approximately 1000 bp) and full-length sequences of both nuclear ribosomal
      internal transcribed spacer regions, including the intervening 5.8S rRNA region (
      approximately 700 bp total). Bayesian phylogenetic analyses of these independent
      data sets reveal congruent genealogical patterns, with all data partitioning and
      combination strategies consistently recovering five allopatric, geographically
      cohesive genetic clades. These clades show an almost complete lack of internal
      genetic divergence, with most individuals sharing a clade-specific, regionally
      widespread haplotype. The geographic distribution of these clades corresponds to
      patterns seen in other upland taxa of the region, possibly indicating coincident
      vicariance. Because of a lack of quantifiable morphological divergence and
      relatively modest levels of genetic divergence, we conservatively refer to the
      geographically cohesive genetic clades as "phylogeographic units", although these
      may actually represent cryptic species. Conservation implications and the
      prospect for future comparative arachnid phylogeography in the southern
      Appalachians are discussed in light of the results presented here.

PMID- 18053751
TI  - Phylogenetic position of the enigmatic genus Psilorhynchus (Ostariophysi:
      Cypriniformes): evidence from the mitochondrial genome.

PMID- 18053753
TI  - Characterisation of Aft1 a Fot1/Pogo type transposon of Aspergillus fumigatus.
AB  - In recent years the filamentous fungus Aspergillus fumigatus has become a
      significant cause of infection in man and as such has become the focus of much
      study. It is thought to be the leading mould pathogen in leukaemia and transplant
      patients and is responsible for mortality in a large number of individuals with
      immunological disorders. In an attempt to develop molecular mutagenesis tools for
      assessment of this organism, the genome of A. fumigatus was analysed to identify
      possible functional transposable elements. An apparently intact Fot1/Pogo type
      transposon with 65% identity to the active Tan1 element of Aspergillus niger was
      identified and designated Aft1. Aft1 is a 1.9kb element present in multiple (>20)
      highly conserved copies. It encodes a 332 amino acid transposase which contains
      all the functional motifs required for transposition. In addition, the
      transposase was expressed in cultures grown at 37 degrees C in all three strains
      assessed and excision analysis suggests Aft1 may be active and of use in
      transposon tagging experiments. Southern hybridisation patterns indicate that
      Aft1 is widely distributed amongst clinical isolates of A. fumigatus with
      considerable variation in genomic localisation. A comprehensive analysis of the
      genomic localisation of Aft1 in the sequenced strain AF293 show that one
      insertion is 30 bases upstream of a predicted gene encoding a G-protein coupled
      receptor. Expression analysis indicates that this gene has been inactivated by
      the insertion.

PMID- 18053755
TI  - [Preimplantation genetic diagnosis (PGD): between fantasy and imprecation!].

PMID- 18053756
TI  - Sonochemically assisted synthesis of zinc-doped maghemite.
AB  - Nanoparticles of zinc-doped maghemite were prepared using ultrasonic radiation.
      As a precursor, a suspension of maghemite in an alkaline aqueous solution of zinc
      nitrate at pH 9 was sonicated. The zinc-doped maghemite nanoparticles were
      investigated by X-ray diffraction, Mossbauer spectroscopy, high-resolution
      electron microscopy (HREM) and SQUID magnetometry. The Mossbauer measurements,
      which cover the temperature range 4.2 K to room temperature, were acquired in
      zero field and an applied field of 5 T. The results show that by using ultrasound
      radiation, zinc Zn2+ can substitute for Fe3+ up to a composition close to zinc
      ferrite (ZnFe2O4), which has a random distribution of Fe3+ ions over both A and B
      sublattices in the spinel structure with an inversity parameter of delta=0.322.
      This leads to a maximum saturation magnetization (Ms) of 64.1 emu/g at 300 K and
      73.5 emu/g at 2 K.

PMID- 18053757
TI  - Dawning of a new era: photomorphogenesis as an integrated molecular network.
AB  - Plant growth is shaped by the dynamic integration of environmental,
      developmental, and metabolic cues. Information from many of these input pathways
      feeds into the highly connected network of small molecule phytohormones. Signal
      transduction components for most plant hormones are known and mapping of hormone
      interactions within the network is well underway. Recent investigations of
      seedling photomorphogenesis, using well-established physiological and genetic
      tools in combination with sophisticated application of newer genomic
      technologies, provide a systems-level view of early seedling development.
      Factors, such as light, the circadian clock, and organ-specific developmental
      programs, profoundly influence the hormone network. The integrative approaches
      described here clarify the mechanisms of signal integration while revealing the
      flexibility of such relationships.

PMID- 18053758
TI  - Genotoxicity testing of fluconazole in vivo and in vitro.
AB  - The genotoxic effects of the antifungal drug fluconazole (trade name triflucan)
      were assessed in the chromosome aberration (CA) test in mouse bone-marrow cells
      in vivo and in the chromosome aberration, sister chromatid exchange (SCE) and
      micronucleus (MN) tests in human lymphocytes. Fluconazole was used at
      concentrations of 12.5, 25.0 and 50.0 mg/kg for the in vivo assay and 12.5, 25.0
      and 50.0 microg/ml were used for the in vitro assay. In both test systems, a
      negative and a positive control (MMC) were also included. Six types of structural
      aberration were observed: chromatid and chromosome breaks, sister chromatid
      union, chromatid exchange, fragments and dicentric chromosomes. Polyploidy was
      observed in both the in vivo and in vitro systems. In the in vivo test,
      fluconazole did not significantly increase the frequency of CA. In the in vitro
      assays, CA, SCE and MN frequencies were significantly increased in a dose
      dependent manner compared with the negative control. The mitotic, replication and
      cytokinesis-block proliferation indices (CBPI) were not affected by treatments
      with fluconazole. According to these results, fluconazole is clastogenic and
      aneugenic in human lymphocytes, but these effects could not be observed in mice.
      Further studies should be conducted in other test systems to evaluate the full
      genotoxic potential of fluconazole.

PMID- 18053759
TI  - Temporal variation in the genotoxic potential of urban air particulate matter.
AB  - The main aim of this study was to compare the genotoxic potential of organic
      extracts from urban air particles collected in three different sampling periods
      in the center of Prague (Czech Republic). For this purpose, we analyzed the DNA
      adduct forming activity of extractable organic matter (EOM) from urban air
      particles <10 microm (PM10) in the human hepatoma cell line HepG2. DNA adducts
      were analyzed by (32)P-postlabelling with nuclease P1 enrichment. PM10
      concentrations were 36.9 microg/m(3), 62.6mug/m(3) and 39.0 microg/m(3), in
      summer 2000, winter 2001 and winter 2005, respectively. The corresponding EOM
      contents were 5.0 microg/m(3) (13.9% of PM10), 14.9 microg/m(3) (23.8%) and 6.7
      microg/m(3) (17.2%). The total DNA adduct levels induced by 10 microg EOM/ml were
      4.7, 19.5 and 37.2 adducts/10(8) nucleotides in summer 2000, winter 2001 and
      winter 2005, respectively. However, when the EOM quantities per cubic meter of
      air were taken into consideration, the summer sample exhibited a 10-fold lower
      genotoxicity than did those of winter, while the difference between the winter
      samples was not significant: 23.4 in summer 2000, 291 in winter 2001 and 249 in
      winter 2005 (in relative units). Although the PM10 concentration in air and the
      EOM content in particles in winter 2005 were significantly lower than in winter
      2001, the genotoxic potential of the ambient air in these samples was almost
      equal. There were significant positive correlations between the B[a]P and c-PAH
      content in EOM from various sampling periods and the total DNA adduct levels
      detected in the EOM-treated samples. These findings support the hypothesis that
      the B[a]P and c-PAH content in EOM is the most important factor that determines
      its genotoxic potential. Thus, estimating the genotoxic potential of the ambient
      air and predicting health risk should be based mainly on the c-PAH concentration
      and the biological activity of the extracts, while the mass of particles and the
      EOM content do not seem to be crucial determinants of ambient air genotoxicity.

PMID- 18053752
TI  - The role of protein synthesis in memory consolidation: progress amid decades of
      debate.
AB  - A major component of consolidation theory holds that protein synthesis is
      required to produce the synaptic modification needed for long-term memory
      storage. Protein synthesis inhibitors have played a pivotal role in the
      development of this theory. However, these commonly used drugs have unintended
      effects that have prompted some to reevaluate the role of protein synthesis in
      memory consolidation. Here we review the role of protein synthesis in memory
      formation as proposed by consolidation theory calling special attention to the
      controversy involving the non-specific effects of a group of protein synthesis
      inhibitors commonly used to study memory formation in vivo. We argue that
      molecular and genetic approaches that were subsequently applied to the problem of
      memory formation confirm the results of less selective pharmacological studies.
      Thus, to a certain extent, the debate over the role of protein synthesis in
      memory based on interpretational difficulties inherent to the use of protein
      synthesis inhibitors may be somewhat moot. We conclude by presenting avenues of
      research we believe will best provide answers to both long-standing and more
      recent questions facing field of learning and memory.

PMID- 18053760
TI  - Spectroscopic investigations into degradation of polymer membranes for fuel cells
      applications.
AB  - The research was focused on synthesis of proton conductive, easily degradable
      polymer membranes, which can be used as a model system to verify the efficiency
      of transition metal ions (TMI) in prevention of polymer degradation. Two polymers
      composed of 2-hydroxyethyl methacrylate (HEMA), 2-acrylamido-2-methyl-1-propane
      sulfonic acid (AMPS), and styrenesulfonic acid (SS) were synthesized. The
      copolymers were characterized by gel permeation chromatography (GPC), elementary
      analysis, and FTIR and fluorescence spectroscopies. The results allowed
      determination of weight-average molecular weight and the copolymer composition.
      The protons of sulfonic groups were substituted by paramagnetic transition metal
      ions of various spin states (Cr(3+), S=3/2 and Mn(2+), S=5/2) with the loading
      varying from 0.5 up to 10 mol%. The effectiveness of spin catalysis was checked
      by EPR. The results obtained indicate enhancement of polymer stability in the
      presence of Mn(2+).

PMID- 18053761
TI  - Ring inversion, structural stability and vibrational assignments of sulfolane c
      C4H8SO2 and 3-sulfolene c-C4H6SO2.
AB  - The structural stability of sulfolane (tetrahydrothiophene1,1-dioxide) and 3
      sulfolene (dihydrothiophene1,1-dioxide) was investigated by DFT-B3LYP and ab
      initio MP2 calculations with 6-311+G**) basis set. The calculated symmetric ring
      puckering potential of 3-sulfolene at the B3LYP level is consistent with a flat
      minimum that corresponds to a planar ring but at the MP2 level with a double
      minimum with a low barrier of about 193 cal mol(-1) to ring planarity in
      reasonable agreement with experimental results. From the calculations at the two
      levels of theory sulfolane was predicted to exist predominantly in the twist
      conformation. The vibrational wavenumbers were calculated at the MP2/6-31G**
      level of theory and the potential energy distributions PED among the symmetry
      coordinates of the normal modes were computed for the low-energy structure of the
      molecules. Complete vibrational assignments were provided on the basis of the
      calculated PED values. The experimental infrared and Raman spectra of the two
      molecules were compared to the calculated ones.

PMID- 18053762
TI  - Predicting computerized physician order entry system adoption in US hospitals:
      can the federal mandate be met?
AB  - OBJECTIVES: The purpose of this study is four-fold. First, the hospitals' current
      level of computerized physician order entry (CPOE) adoption is reported; second,
      internal and external influence factors' roles in determining CPOE adoption rates
      are described; third, the future diffusion rate of CPOE systems in US hospitals
      is empirically predicted; finally, the current technology's state-of-the-art is
      assessed. DATA SOURCE: Secondary data from 3 years of the Leapfrog Group's annual
      survey (2002-2004) of US tertiary-care hospitals. STUDY DESIGN: This study
      estimates CPOE market penetration rates applying technology diffusion theory and
      Bass modeling techniques for three future CPOE adoption scenarios-'Optimistic,'
      'Best estimate', and 'Conservative' are empirically derived. PRINCIPAL FINDINGS:
      Two of the CPOE adoption scenarios have diffusion S-curve that indicates a
      technology will achieve significant market penetration. Under current conditions,
      CPOE adoption in urban hospitals will not reach 80% penetration until 2029.
      CONCLUSIONS: The promise of improved quality of care through medication error
      reductions and significant cost controls prompted the Institute of Medicine to
      call for universal CPOE adoption by 1999. However, the CPOE products available as
      of 2006 represent only a 'second generation technology', characterized by many
      limitations. Without increased external and internal pressures, such CPOE systems
      are unlikely to achieve full diffusion in US hospitals in a timely manner.
      Alternatively, developing a new generation of CPOE technology that is more 'user
      friendly' and easily integrated into hospitals' legacy systems may be a more
      expedient approach to achieving widespread adoption.

PMID- 18053763
TI  - Cortical excitability in Duchenne muscular dystrophy.
AB  - OBJECTIVE: To investigate the probable cortical excitability changes in DMD by
      electrophysiological means. METHODS: Sixteen cases with DMD, 10 age-matched
      control children (CC) and 10 healthy adult volunteers (AC) were studied with a
      transcranial magnetic stimulation (TMS) test battery composed of central
      conduction time, cortical silent period and paired TMS paradigm. RESULTS: There
      were no significant differences between DMD and CC groups except for lower
      amplitude motor responses in DMD cases. These two groups showed a similar pattern
      of excitability with less short interval intracortical inhibitions and shorter
      silent period durations as compared to the AC subjects. CONCLUSIONS: The
      electrophysiological tests performed in our DMD patients did not reveal
      abnormalities caused particularly by the disorder. SIGNIFICANCE: TMS excitability
      studies performed in DMD boys may not provide findings other than those related
      to the developmental age.

PMID- 18053764
TI  - Intraoperative neurophysiological monitoring of the spinal cord during spinal
      cord and spine surgery: a review focus on the corticospinal tracts.
AB  - Recent advances in technology and the refinement of neurophysiological
      methodologies are significantly changing intraoperative neurophysiological
      monitoring (IOM) of the spinal cord. This review will summarize the latest
      achievements in the monitoring of the spinal cord during spine and spinal cord
      surgeries. This overview is based on an extensive review of the literature and
      the authors' personal experience. Landmark articles and neurophysiological
      techniques have been briefly reported to contextualize the development of new
      techniques. This background is extended to describe the methodological approach
      to intraoperatively elicit and record spinal D wave and muscle motor evoked
      potentials (muscle MEPs). The clinical application of spinal D wave and muscle
      MEP recordings is critically reviewed (especially in the field of Neurosurgery)
      and new developments such as mapping of the dorsal columns and the corticospinal
      tracts are presented. In the past decade, motor evoked potential recording
      following transcranial electrical stimulation has emerged as a reliable technique
      to intraoperatively assess the functional integrity of the motor pathways.
      Criteria based on the absence/presence of potentials, their morphology and
      threshold-related parameters have been proposed for muscle MEPs. While the debate
      remains open, it appears that different criteria may be applied for different
      procedures according to the expected surgery-related morbidity and the ultimate
      goal of the surgeon (e.g. total tumor removal versus complete absence of
      transitory or permanent neurological deficits). On the other hand, D wave changes
      -when recordable--have proven to be the strongest predictors of maintained
      corticospinal tract integrity (and therefore, of motor function/recovery).
      Combining the use of muscle MEPs with D wave recordings provides the most
      comprehensive approach for assessing the functional integrity of the spinal cord
      motor tracts during surgery for intramedullary spinal cord tumors. However,
      muscle MEPs may suffice to assess motor pathways during other spinal procedures
      and in cases where the pathophysiology of spinal cord injury is purely ischemic.
      Finally, while MEPs are now considered the gold standard for monitoring the motor
      pathways, SEPs continue to retain value as they provide specificity for assessing
      the integrity of the dorsal column. However, we believe SEPs should not be used
      exclusively--or as an alternative to motor evoked potentials--during spine
      surgery, but rather as a complementary method in combination with MEPs. For
      intramedullary spinal tumor resection, SEPs should not be used exclusively
      without MEPs.

PMID- 18053765
TI  - Assessing patients' satisfaction and intensity of pain as outcomes in the
      management of cancer-related pain.
AB  - This study evaluated clinical outcomes in the management of cancer pain in terms
      of pain severity, pain relief and satisfaction with pain management. It was
      conducted in a large oncology hospital in Athens, Greece and utilized the
      American Pain Society's Patient Outcome Questionnaire. Information was also
      collected about the quality of interpersonal relationships with nurses through
      qualitative comments. A convenience sample of 70 hospitalized adult patients
      constituted the study population. Despite the high levels of pain observed
      indicating ineffective treatment, the subjects reported to be "satisfied" or
      "very satisfied" with the management of their pain and the general care given.
      Several significant differences and relationships were found between the
      variables examined. Nurses had developed therapeutic relationships and effective
      communication with the patients. Further, qualitative comments made by 17
      patients provided rich data of rational and humanistic aspects of nursing.
      Medical and nursing curricula and clinical training in Greece should put more
      emphasis on pain management. Also, efforts should be channeled so that the
      management of pain receives a more organised and formal attention in clinical
      settings. The establishment of pain clinics in Hellenic oncology facilities is a
      clinical priority.

PMID- 18053766
TI  - Therapeutic strategies in the management of patients with chronic hepatitis B
      virus infection.
AB  - Currently available options for the treatment of chronic hepatitis B virus (HBV)
      infection include standard and pegylated interferon alfa and four oral antiviral
      agents (lamivudine, adefovir, entecavir, and telbivudine). These treatment
      strategies are either therapies of finite duration that aim to achieve sustained
      off-therapy responses, or long-term treatments that aim to maintain on-therapy
      remission. Pegylated interferon alfa may offer higher sustained off-therapy
      responses after 1 year, but most patients do not respond. Oral antivirals are the
      only candidates for long-term treatment of patients with chronic HBV infection.
      Viral suppression has favourable effects on patients' outcome and modifies the
      natural history of the disease. Viral resistance is the main drawback of long
      term antiviral therapy. Lamivudine monotherapy is associated with higher
      resistance (year 1, 10-27%; year 2, 37-48%; year 4, 60-65%) than adefovir (year
      1, 0%; year 2, 3%; year 5, 29%) or telbivudine (year 1, 3-4%; year 2, 9-22%).
      Entecavir resistance is rare in naive individuals (year 4, <1%), but increases
      over time in lamivudine-resistant patients (year 4, 43%). The best strategy for
      long-term therapy in chronic HBV infection has yet to be established.

PMID- 18053767
TI  - Lack of effects of vagus nerve stimulation on drug-resistant epilepsy in eight
      pediatric patients with autism spectrum disorders: a prospective 2-year follow-up
      study.
AB  - Vagus nerve stimulation (VNS) therapy has been reported to reduce seizure
      frequency in some children with drug-resistant epilepsy who are not suitable
      candidates for epilepsy surgery. It has been suggested that there may be positive
      cognitive and/or behavioral effects independent of seizure control. We describe
      the effects of VNS with respect to seizure frequency, cognition, and autistic
      symptoms and behavior in eight children and adolescents with medically
      intractable epilepsy and autism. In comparison to baseline, seizure frequency had
      not decreased in anyone in our series at the 2-year follow-up. In three cases,
      minor improvements in general functioning were noted, but there were no positive
      cognitive effects. This open prospective pilot study highlights the need for more
      prospective studies to prevent false expectations of improvement in this severely
      disabled group.

PMID- 18053768
TI  - Supraventricular tachycardia after left atrial ablation of persistent atrial
      fibrillation: what is the mechanism?

PMID- 18053769
TI  - Lethal atrioesophageal fistula after pulmonary vein isolation using high
      intensity focused ultrasound (HIFU).

PMID- 18053770
TI  - Acute defibrillation performance of a novel, non-transvenous shock pathway in
      adult ICD indicated patients.
AB  - OBJECTIVES: The purpose of this study was to evaluate the efficacy of a totally
      subcutaneous, anteroposterior defibrillation shock pathway using a long time
      constant shock waveform that emulates a proposed device having approximately
      twice the capacitance and thus twice the available energy of traditional
      transvenous devices. BACKGROUND: A non-transvenous defibrillation system
      potentially offers advantages over a transvenous system including simplification
      of the implant procedure and reduction of the impact of device complications by
      eliminating the need to place a lead within the heart. Previous non-transvenous
      defibrillation efficacy studies have been reported using anterolateral and
      anterior-anterior shock vectors. An external anteroposterior shock vector has
      demonstrated superior efficacy compared to anterolateral shock vectors but a
      prospective study on an anteroposterior shock vector with implanted electrodes
      has not been previously reported. METHODS: The non-transvenous shock vector
      consisted of an anterior low pectorally-placed active can emulator electrode and
      a posterior subcutaneous coil electrode. The shock waveform was a biphasic with
      50% tilt per phase and a time constant of decay of 12 ms. Defibrillation efficacy
      was characterized using a step-down defibrillation threshold protocol (35 J, 25
      J, 15 J). RESULTS: A total of 33 patients with standard ICD indications were
      enrolled in the study with 32 fully completing the protocol. The patient
      population was 69% male, with a mean age of 59 +/- 12 years. Mean ejection
      fraction was 27 +/- 12%. Of the 32 patients tested, 26 patients (81%) were
      successfully defibrillated at 35 J or less, 18 patients were defibrillated at 25
      J or less and 9 patients were successfully defibrillated at 15 J. CONCLUSIONS:
      Defibrillation using a long time-constant waveform delivered through an
      anteroposterior non-transvenous pathway including a pectoral active can emulator
      electrode and a posterior subcutaneous coil electrode is feasible with over 80%
      of patients defibrillated successfully using 35 J or less.

PMID- 18053771
TI  - Percutaneous epicardial ablation of atrial fibrillation.

PMID- 18053772
TI  - Sprint Fidelis 6949 high-voltage lead appears to be prone to early failure.

PMID- 18053773
TI  - Entering the contract research industry in India.
AB  - India is getting to be known as a hot destination for executing clinical trials.
      It is witnessing the frenzied entry of pharma sponsor companies and contract
      research organizations and the movement of Indian non-healthcare groups into
      clinical research. In this mad melee, what are the determinants of success? How
      real is the promise of clinical research in India and what will make or break a
      new entrant in this business? This article attempts to describe these challenges
      and focuses on the resilient success criteria that the contract clinical research
      industry in India has tested every newcomer against.

PMID- 18053774
TI  - A two stage conditional power adaptive design adjusting for treatment by
      covariate interaction.
AB  - During the design and planning phase of clinical trials, researchers often assume
      that no covariate by treatment interaction exists. This assumption has led to
      many trials being underpowered to detect such interactions and perhaps inaccurate
      interpretation of treatment effects. We propose a two-stage adaptive design that
      incorporates the likely existence of a treatment by covariate interaction into
      the design and implementation of the clinical trial. The information in stage 1
      is used to test for the presence of the covariate by treatment interaction. A
      statistically significant interaction influences how the second stage of the
      trial will be implemented, thereby aiding in the full understanding and
      consequently, an accurate interpretation of the treatment effect. We examine the
      statistical properties of the proposed design using a binary outcome under
      different types of covariate by treatment interactions and treatment allocation
      schemes. A conditional power approach is used to prevent inflation of the overall
      trial type I error rate while maintaining adequate statistical power conditional
      on the statistically significant interaction.

PMID- 18053775
TI  - Spatial and temporal expression of Zimp7 and Zimp10 PIAS-like proteins in the
      developing mouse embryo.
AB  - ZIMP7 and ZIMP10 are two novel human PIAS-like proteins that share a similarity
      beyond the SP-RING Zn-finger domain that characterizes the PIAS family. This
      extended similarity is conserved in proteins of several other species and define
      an independent subfamily. ZIMP10 has been shown to increase the sumoylation of
      the androgen receptor (AR) leading to a stimulation of AR-mediated transcription.
      The Drosophila tonalli (tna) is the ortholog gene of ZIMP7 and ZIMP10 and
      presents genetic interactions with the SWI-SNF complex. Mutations in the tna gene
      produce flies with homeotic phenotypes. In this study, we determined the spatial
      temporal expression pattern of Zimp7 and Zimp10 in mouse embryos from embryonic
      day 7.5 (E7.5), to mid-gestation. We found that these two genes are extensively
      expressed during these embryonic days and present partially overlapping patterns
      with a predomination of the transcripts in the neural tissues at early stages and
      a drop of expression at E12.5. Unlike other PIAS proteins, the tonalli-related
      Zimp genes might be essential for development. Comparison of conserved motifs in
      Zimp7 and Zimp10 protein sequences identified characteristic family domains that
      might be related to their specific biological roles, besides their common role
      previously identified in the sumoylation pathway.

PMID- 18053777
TI  - Editorial for CF pregnancy guidelines.

PMID- 18053776
TI  - Nucleotide excision repair and the degradation of RNA pol II by the
      Caenorhabditis elegans XPA and Rsp5 orthologues, RAD-3 and WWP-1.
AB  - The Caenorhabditis elegans rad-3 gene was identified in a genetic screen for
      radiation sensitive (rad) mutants. Here, we report that the UV sensitivity of rad
      3 mutants is caused by a nonsense mutation in the C. elegans orthologue of the
      human nucleotide excision repair gene XPA. We have used the xpa-1/rad-3 mutant to
      examine how a defect in nucleotide excision repair (NER) perturbs development. We
      find that C. elegans carrying a mutation in xpa-1/rad-3 are hypersensitive and
      hypermutable in response to UV irradiation, but do not display hypersensitivity
      to oxidative stress or show obvious developmental abnormalities in the absence of
      UV exposure. Consistent with these observations, non-irradiated xpa-1 mutants
      have a similar lifespan as wild type. We further show that UV irradiated xpa-1
      mutants undergo a stage-dependent decline in growth and survival, which is
      associated with a loss in transcriptional competence. Surprisingly,
      transcriptionally quiescent dauer stage larvae are able to survive a dose of UV
      irradiation, which is otherwise lethal to early stage larvae. We show that the
      loss of transcriptional competence in UV irradiated xpa-1 mutants is associated
      with the degradation of the large RNA polymerase II (RNA pol II) subunit, AMA-1,
      and have identified WWP-1 as the putative E3 ubiquitin ligase mediating this
      process. The absence of wwp-1 by itself does not cause sensitivity to UV
      irradiation, but it acts synergistically with a mutation in xpa-1 to enhance UV
      hypersensitivity.

PMID- 18053778
TI  - Acute intestinal obstruction as a presentation of cystic fibrosis in infancy.
AB  - Intestinal obstruction and dysmotility occur throughout life in cystic fibrosis
      but rarely present as an acute obstruction beyond the neonatal period. We
      describe the previously unreported occurrence of acute obstruction of the sigmoid
      colon as a presenting feature of cystic fibrosis (CF) in a 6-month infant.

PMID- 18053779
TI  - Fast and direct quantification of adrenal steroids by tandem mass spectrometry in
      serum and dried blood spots.
AB  - We present a fast and reproducible method for steroid analysis (corticosterone,
      deoxycorticosterone, progesterone, 17alpha-hydroxyprogesterone, 11-deoxycortisol,
      21-deoxycortisol, androstenedione, testosterone, dihydrotestosterone and
      cortisol) in small volumes of serum and in dried blood spot samples by LC-MS/MS.
      No derivatisation was needed. LC separation was achieved by using an Atlantis C18
      column and water-methanol-formic acid gradient as a mobile phase and a flow rate
      of 250 microL/min over a run time of 6 min. Steroids were measured in MRM mode
      with electrospray interface (positive ion mode). Validation showed excellent
      precision, sensitivity, recovery and linearity with coefficients of determination
      r2>0.992.

PMID- 18053780
TI  - Mechanism and kinetics of apatite formation on nanocrystalline TiO2 coatings: a
      quartz crystal microbalance study.
AB  - Apatite (Ca5(PO4)3OH) has long been considered as an excellent biomaterial to
      promote bone repairs and implant. Apatite formation induced by negatively charged
      nanocrystalline TiO2 coatings soaked in simulated body fluid (SBF) was
      investigated using in situ quartz crystal microbalance (QCM), scanning electron
      microscopy (SEM), Fourier-transformed infrared spectroscopy (FTIR), X-ray
      diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDX) techniques, and
      factors affecting its formation such as pH, size of TiO2 particles and thickness
      of TiO2 coatings, were discussed in detail. Two different stages were clearly
      observed in the process of apatite precipitation, indicating two different
      kinetic processes. At the first stage, the calcium ions in SBF were initially
      attracted to the negatively charged TiO2 surface, and then the calcium titanate
      formed at the interface combined with phosphate ions, consequently forming
      apatite nuclei. After the nucleation, the calcium ions, phosphate ions and other
      minor ions (i.e. CO3(2-) and Mg2+) in supersaturated SBF deposited spontaneously
      on the original apatite coatings to form apatite precipitates. In terms of the in
      situ frequency shifts, the growth-rate constants of apatite (K1 and K2) were
      estimated, respectively, at two different stages, and the results were (1.96+/
      0.14)x10(-3)s(-1) and (1.28+/-0.10)x10(-4)s(-1), respectively, in 1.5 SBF
      solution. It was found that the reaction rate at the first stage is obviously
      higher than that at the second stage.

PMID- 18053781
TI  - A randomised study of ilio-inguinal nerve blocks following inguinal hernia
      repair: a stopped randomised controlled trial.
AB  - BACKGROUND: Local anaesthetic use for post-operative pain control is widely used
      following open inguinal hernia repair but this is not without risk. The aim of
      this study was to compare ilio-inguinal nerve block and wound irrigation in
      patients undergoing open inguinal hernia repair under general anaesthetic in a
      randomised, double blind, placebo controlled trial. METHODS: Adult patients
      admitted for unilateral primary open mesh repair of an inguinal hernia were
      recruited. The patients received a standard general anaesthetic. Prior to skin
      incision, an ilio-inguinal injection was performed by the anaesthetist with
      either ropivicaine or normal saline. Prior to closure of the wound, the wound was
      irrigated with either ropivicaine or normal saline. Post-operatively, all
      patients received fentynal patient controlled analgesia and regular oral
      analgesia. Pain scores and visual analogue scores were recorded until discharge.
      Patients were then contacted by telephone at 24h, 48h, 2weeks and 4weeks post
      operatively and asked a standard series of questions, mainly related to post
      operative pain. RESULTS: After 12 patients had been recruited the trial was
      stopped as 5 of the 8 patients who received an ilio-inguinal nerve block suffered
      a neurological complication. CONCLUSION: Ilio-inguinal nerve block with
      ropivicaine should be avoided.

PMID- 18053782
TI  - Solitary fibrous tumor of the liver: report of a rare case and review of the
      literature.
AB  - Solitary fibrous tumor of the liver is extremely rare, with only 38 cases
      reported in the literature. We present one case of a SFT originating from the
      caudate lobe of the liver, treated by surgical resection and review the previous
      reported cases.

PMID- 18053783
TI  - Abnormalities of the fetal bladder.
AB  - This review aims to outline the management of a fetus in whom a distended bladder
      or an absent bladder has been identified during prenatal fetal screening. The
      causes, pre-delivery and immediate post-delivery treatment options are discussed,
      as well as prognosis.

PMID- 18053784
TI  - Experimental study on axial pedicled composite flap prefabrication with high
      density porous polyethylene implants: medporocutaneous flap.
AB  - Composite flaps including soft tissues with bone or cartilage are widely used in
      reconstruction of three-dimensional defects, but have some disadvantages. Flap
      prefabrication with alloplastic implants is an alternative procedure. Axial
      pattern vascularised high density porous polyethylene (HDPP) implants are capable
      of sustaining skin grafts. The purpose of this study was to examine the
      vascularisation pattern of the skin island in a composite flap prefabrication
      model prepared with vascularised HDPP implants. Forty male Wistar rats divided
      into four groups were used. A 9.5 x 6 x 2 mm HDPP block was centered on the
      dissected saphenous pedicle and anchored under the abdominal skin in the
      experimental group I (n=10). In experimental group II (n=10) saphenous artery and
      vein were put between the skin and the implant. Thus, the structures were laid as
      skin, HDPP block, pedicle in experimental group I and skin, pedicle, HDPP block
      in experimental group II. HDPP block-implanted and pedicle-implanted only groups
      served as control groups I and II, respectively. Eight weeks after
      prefabrication, skin islands 1.5 x 5 cm in size incorporated with implants were
      elevated based on saphenous vessels in the experimental groups and skin islands
      only based on the pedicle in control group II. Skin islands of the same
      dimensions were raised as grafts in control group I. Nylon sheets were put under
      the flaps and grafts to prevent vascularisation from the recipient bed. Flap
      viability was assessed by measuring the surface area on the 7th day. Total
      necrosis developed in composite grafts of control group I. Flap survival was
      higher in experimental group II and control group II (45% and 46.8%) than in
      group I (29.28%). Histologic studies demonstrated fibrovascular ingrowth into the
      HDPP implants, except in control group I, with significant inflammatory response
      and necrosis. Vascularisation of skin and implants from the pedicle was seen also
      microangiographically. In conclusion, a composite flap prefabrication model
      including vascularised HDPP implant, skin and vascular carrier was developed.
      This new flap was termed a 'medporocutaneous flap'.

PMID- 18053785
TI  - Precision and symmetry in aesthetic plastic surgery "What Immortal hand or eye
      could frame thy fearful symmetry" (William Blake).
AB  - Attaining symmetry is indispensable for a successful aesthetic outcome of plastic
      surgical procedures. In this paper we propose a simple technique for accurate
      placement of markings during surgery. This technique is simple, quick and does
      not require any special instruments. The method is easily reproducible and can be
      used intraoperatively to position the symmetrical points accurately.

PMID- 18053786
TI  - A 6.9 Mb 1qter deletion/4.4 Mb 18pter duplication in a boy with extreme
      microcephaly with simplified gyral pattern, vermis hypoplasia and corpus callosum
      agenesis.
AB  - We here report a boy presenting with developmental delay, growth retardation,
      facial dysmorphisms, vermis hypoplasia, micropolygyria and corpus callosum
      agenesis. Conventional and high resolution cytogenetic analyses were normal but
      high resolution oligonucleotide array-CGH, performed at the age of 4 years,
      allowed the characterisation of a de novo 6.9 Mb 1qter deletion/4.4 Mb 18pter
      duplication. Numerous 1qter deletions have already been described associated with
      brain malformations. Among 1q44 deleted genes, AKT3 is the strongest candidate
      gene for vermis hypoplasia and corpus callosum agenesis.

PMID- 18053787
TI  - [A case-control study of health benefits in patients with moderate renal
      failure].
AB  - In order to evaluate medical management in patients with renal failure before
      dialysis, we conducted a case-control study to analyze the health benefits in 914
      moderate renal failure patients with Cockcroft clearance between 30 and 60
      ml/min. Health benefits reimbursed by the Social Security in this population were
      compared with those in 1828 controls randomly chosen in the Social Security files
      but matched by age and gender. Mean age of the participants was 73+/-11 year-old,
      67% were women, Cockcroft clearance was 48+/-8 ml/min. Number of hospitalizations
      and hospitalization durations were not different between the two populations.
      Conversely, cases had more specialized outpatients' clinics in cardiology but not
      in nephrology or urology. Cases had more biological tests and radiological exams
      and had taken more medicines. For biology, cases had more often renal function
      tests and markers of renal dysfunction tests than controls. Cases had taken more
      medicines than controls for erythropoietin, diuretics, renin-angiotensin
      blockers, hypoglycemic drugs, and anticoagulants. Patients with mild renal
      failure had higher health benefits than controls for outpatients' clinics in
      cardiology, for biological tests, for radiological exams, and for some medicines.

PMID- 18053788
TI  - Multi-modality study of the compositional and mechanical implications of
      hypomineralization in a rabbit model of osteomalacia.
AB  - Osteomalacia is characterized by hypomineralization of the bone associated with
      increased water content. In this work we evaluate the hypotheses that 1) 3D solid
      state magnetic resonance imaging (MRI) of (31)P (SSI-PH) and (1)H (SSI-WATER) of
      cortical bone can quantify the key characteristics of osteomalacia induced by low
      phosphate diet; and 2) return to normophosphatemic diet (NO) results in recovery
      of these indices to normal levels. Twenty female five-week old rabbits were
      divided into four groups. Five animals were fed a normal diet for 8 weeks (NOI);
      five a hypophosphatemic diet (0.09%) for the same period to induce osteomalacia
      (HYI). To examine the effect of recovery from hypophosphatemia an additional five
      animals received a hypophosphatemic diet for 8 weeks, after which they were
      returned to a normal diet for 6 weeks (HYII). Finally, five animals received a
      normal diet for the entire 14 weeks (NOII). The NOI and HYI animals were
      sacrificed after 8 weeks, the NOII and HYII groups after 14 weeks. Cortical bone
      was extracted from the left and right tibiae of all the animals. Water content
      was measured by SSI-WATER and by a previously reported spectroscopic proton
      deuteron nuclear magnetic resonance (NMR) exchange technique (NMR-WATER),
      phosphorus content by SSI-PH. All MRI and NMR experiments were performed on a 9.4
      T spectroscopy/micro-imaging system. Degree of mineralization of bone (DMB) was
      measured by micro-CT and elastic modulus and ultimate strength by 3-point
      bending. The following parameters were lower in the hypophosphatemic group:
      phosphorus content measured by SSI-PH (9.5+/-0.4 versus 11.1+/-0.3 wt.%,
      p<0.0001), ash content (63.9+/-1.7 versus 65.4+/-1.1 wt.%, p=0.05), ultimate
      strength, (96.3+/-16.0 versus 130.7+/-6.4 N/mm(2), p=0.001), and DMB (1115+/-28
      versus 1176+/-24 mg/cm(3), p=0.003); SSI-WATER: 16.1+/-1.5 versus 14.4+/-1.1
      wt.%, p=0.04; NMR-WATER: 19.0+/-0.6 versus 17.4+/-1.2 wt.%, p=0.01. Return to a
      normophosphatemic diet reduced or eliminated these differences (SSI-PH: 9.5+/-0.9
      versus 10.6+/-0.8 wt.%, p=0.04; DMB: 1124+/-31 versus 1137+/-10 mg/cm(3), p=0.2;
      US: 95.6+/-18.6 versus 103.9+/-7.5 N/mm(2), p=0.2; SSI-WATER: 12.4+/-0.6 versus
      12.2+/-0.3 wt.%, p=0.3) indicating recovery of the mineral density close to
      normal levels. Phosphorus content measured by SSI-PH was significantly correlated
      with DMB measured by micro-CT (r(2)=0.47, p=0.001) as well as with ultimate
      strength (r(2)=0.54, p=0.0004). The results show that the methods presented have
      potential for in situ assessment of mineralization and water, both critical to
      the bone's mechanical behavior.

PMID- 18053789
TI  - Cost effectiveness of hormone therapy in women at high risks of fracture in
      Sweden, the US and the UK--results based on the Women's Health Initiative
      randomised controlled trial.
AB  - OBJECTIVE: The purpose of the study was to assess the cost effectiveness of
      hormone therapy (HT) for postmenopausal women without menopausal symptoms at an
      increased risk of fracture in Sweden, the UK and the US. METHODS: Using a state
      transition model, the cost effectiveness of 50 year old women was assessed based
      on a societal perspective and the medical evidence found in the Women Health
      Initiative (WHI) trials. The model had a lifetime horizon divided into cycle
      lengths of 1 year and comprised the following disease states: hip fracture,
      vertebral fracture, wrist fracture, breast cancer, colorectal cancer, coronary
      heart disease, stroke and venous thromboembolic events. An intervention was
      modelled by its impact on the disease risks during and after the cessation of
      treatment. The model required data on clinical effects, risks, mortality rates,
      quality of life weights and costs valid for Sweden, the UK and the US. The main
      outcome of the model was cost per QALY gained of HT compared to no treatment.
      RESULTS: The results indicated that HT compared to no treatment was cost
      effective for most sub-groups of hysterectomised women, whereas for women with an
      intact uterus without a previous fracture, HT was commonly dominated by no
      treatment. Fracture risks were the single most important determinant of the cost
      effectiveness results. CONCLUSIONS: HT is cost-effective in women with a
      hysterectomy irrespective of prior fracture status. In women with an intact
      uterus, opposed HT was cost-effective in those with a prior vertebral fracture,
      but cost-ineffective in women without a prior vertebral fracture. Even though HT
      is found cost-effective for a selection of osteoporotic women, it is unlikely to
      be considered for first-line therapy for osteoporosis because bisphosphonates
      have shown a similar reduction in fracture risks but without an increased risk of
      adverse events.

PMID- 18053790
TI  - Stimulation of the DNA unwinding activity of human DNA helicase II/Ku by
      phosphorylation.
AB  - The Ku autoantigen is a heterodimeric protein of 70- and 83-kDa subunits, endowed
      with duplex DNA end-binding capacity and DNA helicase activity (Human DNA
      Helicase II, HDH II). HDH II/Ku is well established as the DNA binding component,
      the regulatory subunit as well as a substrate for the DNA-dependent protein
      kinase DNA-PK, a complex involved in the repair of DNA double-strand breaks and
      in V(D)J recombination in eukaryotes. The effects of phosphorylation by this
      kinase on the helicase activity of Escherichia coli-produced HDH II/Ku were
      studied. The rate of DNA unwinding by recombinant HDH II/Ku heterodimer is
      stimulated at least fivefold upon phosphorylation by DNA-PK(cs). This stimulation
      is due to the effective transfer of phosphate residues to the helicase rather
      than the mere presence of the complex. In vitro dephosphorylation of HeLa
      cellular HDH II/Ku caused a significant decrease in the DNA helicase activity of
      this enzyme.

PMID- 18053791
TI  - A comparative molecular dynamics analysis of the amyloid beta-peptide in a lipid
      bilayer.
AB  - Because the amyloid beta-peptide (Abeta) functions as approximately half of the
      transmembrane domain of the amyloid precursor protein and interaction of Abeta
      with membranes is proposed to result in neurotoxicity, the association of Abeta
      with membranes likely is important in the etiology of Alzheimer's disease. Atomic
      details of the interaction of Abeta with membranes are not accessible with most
      experimental techniques, but computational methods can provide this information.
      Here, we present the results of ten 100-ns molecular dynamics (MD) simulations of
      the 40-residue amyloid beta-peptide (Abeta40) embedded in a
      dipalmitoylphosphatidylcholine (DPPC) bilayer. The present study examines the
      effects of insertion depth, protonation state of key residues, and ionic strength
      on Abeta40 in a DPPC bilayer. In all cases, a portion of the peptide remained
      embedded in the bilayer. In the case of deeper insertion depth, Abeta40 adopted a
      near-transmembrane orientation, drawing water molecules into the bilayer to
      associate with its charged amino acids. In the case of shallower insertion, the
      most widely-accepted construct, the peptide associated strongly with the membrane
      water interface and the phosphatidylcholine headgroups of the bilayer. In most
      cases, significant disordering of the extracellular segment of the peptide was
      observed, and the brief appearance of a beta-strand was noted in one case. Our
      results compare well with a variety of experimental and computational findings.
      From this study, we conclude that Abeta associated with membranes is dynamic and
      capable of adopting a number of conformations, each of which may have
      significance in understanding the progression of Alzheimer's disease.

PMID- 18053792
TI  - Differential regulation of psbA and psbD gene expression, and the role of the
      different D1 protein copies in the cyanobacterium Thermosynechococcus elongatus
      BP-1.
AB  - In Thermosynechococcus elongatus BP-1, which is the preferred organism in recent
      structural studies of PSII, three psbA and two psbD genes code for three D1 and
      one D2 protein isoforms, respectively. The regulation and function of these genes
      and protein products is largely unknown. Therefore, we used quantitative RT-PCR
      to follow changes in the mRNA level of the respective genes, in combination with
      biophysical measurements to detect changes in the electron transport activity of
      Photosystem II under exposure to different visible and UV light, and temperature
      conditions. In cells which are acclimated to 40 micromol m(-2)s(-1) growth light
      conditions at 40 degrees C the main populations of the psbA and psbD transcripts
      arise from the psbA1 and psbD1 genes, respectively. When the temperature is
      raised to 60 degrees C psbA1 becomes the single dominating psbA mRNA species.
      Upon exposure of the cells to 500 micromol m(-2)s(-1) intensity visible light
      psbA3 replaces psbA1 as the dominating psbA mRNA species, and psbD2 increases at
      the expense of psbD1. UV-B radiation also increases the abundance of psbA3, and
      psbD2 at the expense of psbA1 and psbD1, respectively. From the different extent
      of total D1 protein loss in the absence and presence of lincomycin it was
      estimated that the PsbA3 protein isoform replaces PsbA1 in about 65% of PSII
      centers after 2 h of high light acclimation. Under the conditions of different
      psbA transcript distributions chlorophyll fluorescence and thermoluminescence
      measurements were applied to monitor charge recombination characteristics of the
      S2Q(A)(-) and S2Q(B)(-) states. We obtained faster decay of flash-induced
      chlorophyll fluorescence in the presence of DCMU, as well as lower peak
      temperature of the Q and B thermoluminescence bands when PsbA3 replaced PsbA1 as
      the main D1 protein isoform. The relevance of dynamic changes in the abundance of
      psbA and psbD transcript levels, as well as D1 protein isoforms in the
      acclimation of T. elongatus to changing environmental conditions is discussed.

PMID- 18053793
TI  - Identification of new functions of Ca2+ release from intracellular stores in
      central nervous system.
AB  - Ca(2+) release from intracellular stores regulates muscle contraction and a vast
      array of cell functions, but its role in the central nervous system (CNS) has not
      been completely elucidated. A new method of blocking IP(3) signaling by
      artificially expressing IP(3) 5-phosphatase has been used to clarify the
      functions of intracellular Ca(2+) mobilization in CNS. Here I review two of such
      functions: the activity-dependent synaptic maintenance mechanism and the
      regulation of neuronal growth by spontaneous Ca(2+) oscillations in astrocytes.
      These findings add new bases for better understanding CNS functions and suggest
      the presence of as yet unidentified neuronal and glial functions that are
      regulated by Ca(2+) store-dependent Ca(2+) signaling.

PMID- 18053794
TI  - Specificity protein 1 (Sp1) plays role in regulating LIM homeodomain
      transcription factor Lhx4 gene expression.
AB  - Both Sp-family factor Specificity protein 1 (Sp1) and LIM homeodomain
      transcription factor Lhx4 are involved in regulating the development of pituitary
      gland and nervous system in mammals. Sp1 gene mutation results in death of mouse
      embryo around day 11 of gestation, and mouse anterior pituitary development is
      severely hypoplastic after Lhx4 mutation. While Sp1 interacts with the related
      Lhx3 gene it is unclear whether Sp1 and Lhx4 also interact to regulate their
      physiological functions. The present study demonstrates that Lhx4 promoter is
      TATA-less and GC-rich and these sequences are conserved in different species. We
      have shown using site-directed mutagenesis and the Dual-Glo Luciferase Assay
      System that within the -515 to +36bp basic activity regions of hLhx4 promoter the
      GC boxes were important for Sp1 regulation of the hLhx4 promoter. The
      electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation
      (ChIP) experiments confirmed that Sp1 interacted with Lhx4 by directly binding to
      GC boxes located in Lhx4 promoter. We conclude Sp1 directly regulates Lhx4 gene
      expression.

PMID- 18053795
TI  - Interaction sites among phospholamban, sarcolipin, and the sarco(endo)plasmic
      reticulum Ca(2+)-ATPase.
AB  - A robust cross-link between Gln(23) in phospholamban (PLN) and Lys(328) in the
      sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA1a) is formed in the presence or
      absence of oxidant and is susceptible to both PLN phosphorylation and SERCA1a
      Ca(2+) binding. This cross-link provides precisely the evidence needed to support
      our earlier proposal that collision of the PLN transmembrane helix at Asn(27)
      with the cytosolic extension of M4 at Leu(321) leads to unwinding of the helix.
      In a study of site-specific interactions among PLN, sarcolipin (SLN), and
      SERCA1a, we determined that mutations of some specific amino acids in PLN or SLN
      diminish either the super-inhibition imposed on SERCA1a function by the PLN-SLN
      binary complex or the physical interactions between PLN and SLN or both. These
      results have led to a revision of our earlier model for the PLN-SLN-SERCA1a
      complex.

PMID- 18053796
TI  - Cardiac proteasome dysfunction during cold ischemic storage and reperfusion in a
      murine heart transplantation model.
AB  - Recent observations suggest that the ubiquitin-proteasome system (UPS)
      contributes to the pathophysiology of myocardial ischemia-reperfusion injury.
      Since its regulation during cold ischemia-reperfusion is unknown, we evaluated
      the cardiac UPS in a model of heart transplantation in mice. Cardiac
      ubiquitylation rates and ubiquitin-protein conjugates increased after 3h of cold
      ischemia (CI) and normalized post-transplant. 20S proteasome content and
      proteasome peptidase activities were unchanged after CI. 4h/24h post-transplant
      20S proteasome concentrations decreased and chymotryptic-like but not tryptic
      like proteasome peptidase activity was inactivated. Epoxomicin sensitivity of the
      proteasome increased 5.7-fold during CI and normalized 4h/24h post-transplant.
      This was accompanied by the disappearance of a 13.5 kDa-ubiquitin-conjugate
      during CI that could be attenuated by addition of epoxomicin to the preservation
      fluid. We conclude that substrate specificity of the proteasome changes during
      cold ischemia and that proteasome inhibition preserves the physiological
      ubiquitin-protein conjugate pool during organ preservation. Reduced proteasome
      activity during reperfusion is caused by a decrease in proteasome content and
      enzyme inhibition.

PMID- 18053797
TI  - Apple aminopropyl transferase, MdACL5 interacts with putative elongation factor 1
      alpha and S-adenosylmethionine synthase [corrected].
AB  - Several lines of evidence suggest different allocations of the physiological
      roles of aminopropyl transferase genes, SPMS and ACL5 in plants. To get deeper
      insights into the physiological role of apple ACL5 (MdACL5), we performed yeast
      two-hybrid (Y2H) assay to identify proteins which interact with MdACL5. After
      intense screening processes, including the swapping of the bait and prey vectors
      and in vitro coimmunoprecipitation, we identified three MdACL5-interacting
      proteins: putative translation elongation factor 1A (eEF-1A), putative S-adenosyl
      l-methionine synthetase (SAMS) and an unknown protein. Results from Y2H and RNA
      gel blot analysis suggested the involvement of MdACL5 and eEF-1A or SAMS
      complexes in the plant growth and development of the organized tissues and/or
      organs.

PMID- 18053798
TI  - Rosiglitazone transiently disturbs calcium homeostasis in monocytic cells.
AB  - The PPARgamma agonist Rosiglitazone exerts anti-hyperglycaemic effects by
      regulating the long-term expression of genes involved in metabolism,
      differentiation and inflammation. In the present study, Rosiglitazone treatment
      rapidly inhibited (5-30 min) the ER Ca(2+) ATPase SERCA2b in monocytic cells
      (IC(50)=1.88 microM; p<0.05), thereby disrupting short-term Ca(2+) homeostasis
      (resting [Ca(2+)](cyto)=121.2+/-2.9% basal within 1h; p<0.05). However, extended
      Rosiglitazone treatment (72 h) induced dose-dependent SERCA2b up-regulation, and
      restored calcium homeostasis, in monocytic cells (SERCA2b mRNA: 138.7+/-5.7%
      basal (1 microM)/215.0+/-30.9% basal (10 microM); resting [Ca(2+)](cyto)=97.3+/
      8.3% basal (10 microM)). As unfavourable cardiovascular outcomes, possibly
      related to disrupted cellular Ca(2+) homeostasis, have been linked to
      Rosiglitazone, this effect may be of clinical interest. In contrast, in PPRE
      luciferase reporter-gene assays, Rosiglitazone induced non-dose-dependent
      PPARgamma-dependent effects (1 microM: 152.5+/-4.9% basal; 10 microM: 136.1+/
      5.1% basal (p<0.05 for 1 microM vs. 10 microM)). Thus, we conclude that
      Rosiglitazone can exert PPARgamma-independent non-genomic effects, such as the
      SERCA2b inhibition seen here, but that long-term Rosiglitazone treatment did not
      perturb resting [Ca](cyto) in this study.

PMID- 18053799
TI  - Leukotriene C4 synthase promoter driven expression of GFP reveals cell
      specificity.
AB  - Leukotriene C(4) synthase is a key enzyme in leukotriene biosynthesis. Its gene
      has been cloned and mapped to mouse chromosome 11. Expression occurs in cells of
      myeloid origin and also in the choroid plexus, the hypothalamus and the medial
      eminence of mouse brain. In this study a vector that expresses enhanced green
      fluorescent protein (eGFP) under the control of the mouse leukotriene C(4)
      synthase promoter was constructed and used to study promoter activity in
      different cell lines. Specific eGFP expression was observed in human monocytic
      leukemia (THP-1) and rat basophilic leukemia (RBL-1) myeloid cells which both
      express leukotriene C(4) synthase, but not in human embryonic kidney (HEK293/T)
      epithelial cells which do not express this enzyme. In the myeloid cells, but not
      in the epithelial cells, we observed that the leukotriene C(4) synthase promoter
      activity was stimulated by 12-O-tetradecanoylphorbol-13-acetate and all-trans
      retinoic acid. In contrast dimethyl sulfoxide did not affect promoter activity.

PMID- 18053800
TI  - Role of non-kinase activity of myosin light-chain kinase in regulating smooth
      muscle contraction, a review dedicated to Dr. Setsuro Ebashi.
AB  - Myosin light-chain kinase (MLCK) of smooth muscle consists of an actin-binding
      domain at the N-terminal, the catalytic domain in the central portion, and the
      myosin-binding domain at the C-terminal. The kinase activity is mediated by the
      catalytic domain that phosphorylates the myosin light-chain of 20kDa (MLC20),
      activating smooth muscle myosin to interact with actin. Although the regulatory
      role of the kinase activity is well established, the role of non-kinase activity
      derived from actin-binding and myosin-binding domains remains unknown. This
      review is dedicated to Dr. Setsuro Ebashi, who devoted himself to elucidating the
      non-kinase activity of MLCK after establishing calcium regulation through
      troponin in skeletal and cardiac muscles. He proposed that the actin-myosin
      interaction of smooth muscle could be activated by the non-kinase activity of
      MLCK, a mechanism that is quite independent of MLC20 phosphorylation. The authors
      will extend his proposal for the role of non-kinase activity. In this review, we
      express MLCK and its fragments as recombinant proteins to examine their effects
      on the actin-myosin interaction in vitro. We also down-regulate MLCK in the
      cultured smooth muscle cells, and propose that MLC20 phosphorylation is not
      obligatory for the smooth muscle to contract.

PMID- 18053801
TI  - Inhibition of tumor-stromal interaction through HGF/Met signaling by valproic
      acid.
AB  - Hepatocyte growth factor (HGF), which is produced by surrounding stromal cells,
      including fibroblasts and endothelial cells, has been shown to be a significant
      factor responsible for cancer cell invasion mediated by tumor-stromal
      interactions. We found in this study that the anti-tumor agent valproic acid
      (VPA), a histone deacetylase (HDAC) inhibitor, strongly inhibited tumor-stromal
      interaction. VPA inhibited HGF production in fibroblasts induced by epidermal
      growth factor (EGF), platelet-derived growth factor, basic fibroblast growth
      factor, phorbol 12-myristate 13-acetate (PMA) and prostaglandin E(2) without any
      appreciable cytotoxic effect. Other HDAC inhibitors, including butyric acid and
      trichostatin A (TSA), showed similar inhibitory effects on HGF production
      stimulated by various inducers. Up-regulations of HGF gene expression induced by
      PMA and EGF were also suppressed by VPA and TSA. Furthermore, VPA significantly
      inhibited HGF-induced invasion of HepG2 hepatocellular carcinoma cells. VPA,
      however, did not affect the increases in phosphorylation of MAPK and Akt in HGF
      treated HepG2 cells. These results demonstrated that VPA inhibited two critical
      processes of tumor-stromal interaction, induction of fibroblastic HGF production
      and HGF-induced invasion of HepG2 cells, and suggest that those activities serve
      for other anti-tumor mechanisms of VPA besides causing proliferation arrest,
      differentiation, and/or apoptosis of tumor cells.

PMID- 18053802
TI  - Redox-dependent structural ambivalence of the cytoplasmic domain in the inner ear
      specific cadherin 23 isoform.
AB  - Cadherin 23 (Cdh23), an essential factor in inner ear mechano-electric
      transduction, exists in two alternatively spliced forms, Cdh23(+68) and Cdh23(
      68), depending on the presence and absence of exon 68. Cdh23(+68) is inner ear
      specific. The exon 68-corresponding region confers an alpha-helical configuration
      upon the cytoplasmic domain (Cy) and includes a cysteine residue, Cys(3240). We
      demonstrate here that Cy(+68) as well as the transmembrane (TM) plus Cy(+68)
      region is present in two different forms in transfected cells, reduced and non
      reduced, the latter existing in more compact configuration than the former. The
      observed characteristic of Cy(+68) was completely abolished by Cys(3240)Ala
      substitution. Treatment of TMCy(+68)-transfected cells with diethyl maleate, a
      glutathione depleting reagent, resulted in conversion of the non-reduced to the
      reduced form of TMCy(+68), suggesting glutathione to be a Cys(3240)-binding
      partner. Multiple alignment of mammalian Cdh23Cy sequences indicated the
      occurrence of conformation-inducible Cys in Cdh23Cy of mammals, but not lower
      vertebrates. The implications of Cys-dependent structural ambivalence of Cdh23 in
      inner ear mechanosensation are discussed.

PMID- 18053803
TI  - Anaerobic alkane-degrading strain AK-01 contains two alkylsuccinate synthase
      genes.
AB  - The sulfate-reducing strain AK-01 activates alkanes via addition of the
      subterminal carbon to the double bond of fumarate. This reaction is similar to
      the action of the glycyl radical enzyme benzylsuccinate synthase (Bss). It was
      hypothesized that strain AK-01 possesses a similar enzyme. Degenerate bssA
      primers and inverse PCR were used to amplify two unlinked genes (assA1 and
      assA2), which encode catalytic subunits of glycyl radical type enzymes.
      Subsequent genome sequencing of AK-01 revealed two ass operons. SDS-PAGE analysis
      of AK-01 grown on n-hexadecane revealed a 95-kDa protein which is absent in
      hexadecanoate-grown cells. LC-MS/MS data obtained from a tryptic digest of this
      protein match the deduced amino acid sequence encoded by assA1, thus confirming
      AssA1's involvement in alkane metabolism. This report is the first description of
      a gene involved in anaerobic n-alkane metabolism in a sulfate-reducer and
      provides evidence for a novel glycyl radical enzyme.

PMID- 18053804
TI  - Comparative effects of sodium pyrithione evoked intracellular calcium elevation
      in rodent and primate ventral horn motor neurons.
AB  - Oral administration of sodium pyrithione (NaP) causes hindlimb weakness in
      rodents, but not in primates. Previous work using Aplysia neurons has
      demonstrated that NaP produces a persistent influx of Ca(2+) ions across the
      plasma membrane. To determine whether this also occurs in mammalian neurons and
      whether this could underlie the inter-species difference between rodents and
      primates, we have tested the effects of NaP on intracellular Ca(2+) levels
      ([Ca(2+)](i)) in rat and monkey motor neurons in vitro. Motor neurons present in
      spinal cord slices from rhesus monkey embryos (E37 and 56) and from rat E16 were
      dissected and cultured on glass coverslips. Following 2 weeks (rhesus) or 2-3
      days (rat) in culture, neurons were loaded with fura-PE3/AM, and examined for
      [Ca(2+)](i) changes in response to NaP. Rhesus motor neurons were identified by
      immunostaining for Islet-1 (MN specific antigen) and neuron specific enolase
      (NSE). Motor neurons from both species exhibited dose-dependent NaP-evoked
      increases in [Ca(2+)](i) However, the dose-response curve for the Rhesus motor
      neurons was significantly shifted to the right of the rat dose-response curve,
      whereas the overall amplitude of the Ca(2+) rise was similar in both species. As
      shown previously for the Aplysia neurons, the action of NaP is attenuated by SKF
      96365, an inhibitor of store-operated calcium entry. In contrast the action of
      NaP is unaffected by nifedipine and tetrodotoxin, blockers of voltage-dependent
      Ca(2+) and Na(+) channels, respectively, or by ouabain, an inhibitor of the
      plasma membrane Na(+)/K(+) ATPase. Our results indicate that the NaP-induced
      increase in [Ca(2+)](i) is conserved across species and suggest that the
      toxicological sensitivity of rodent over primate to pyrithione could be due to
      the enhanced sensitivity of rodent motor neurons to NaP-evoked intracellular
      Ca(2+) elevation.

PMID- 18053805
TI  - Secretory signal sequence non-optimal codons are required for expression and
      export of beta-lactamase.
AB  - In this study we altered the codon usage in the signal sequence of the bla gene,
      encoding beta-lactamase in Escherichia coli. Changing all of the thirteen non
      optimal codons to optimal lowered expression 4-fold as measured by minimum
      inhibitory concentration (MIC) to the beta-lactam antibiotic ampicillin. The
      difference in ampicillin resistance was reduced at 28 degrees C compared to
      expression at 37 degrees C, suggesting that the optimised bla allele is misfolded
      and degraded by heat-shock regulated proteases. A screen was carried out,
      designed specifically to identify revertants with changes in codon usage
      resulting in higher MIC to ampicillin. The nine revertants revealed by this
      method all had optimal to non-optimal codon changes in the signal sequence. These
      results, and those of our previous study with maltose binding protein model
      system, confirm that non-optimal codons are important for expression and export
      of secretory proteins via both the SecB-dependent and -independent pathways.

PMID- 18053806
TI  - A citrus polymethoxyflavonoid, nobiletin, is a novel MEK inhibitor that exhibits
      antitumor metastasis in human fibrosarcoma HT-1080 cells.
AB  - The activation of mitogen-activated protein/extracellular signal-regulated kinase
      (MEK) is well known to be associated with tumor invasion and metastasis. We
      previously reported that a polymethoxyflavonoid, nobiletin (5,6,7,8,3',4'
      hexamethoxyflavone), derived from Citrus depressa (Hayata), inhibits the
      phosphorylation of MEK and thereby suppresses matrix metalloproteinase (MMP)
      expression in a tumor-metastasis stimulator, 12-O-tetradecanoyl phorbol 13
      acetate (TPA)-stimulated human fibrosarcoma HT-1080 cells [Mol. Cancer Ther. 3
      (2004) 839-847]. In the present study, we investigated whether or not nobiletin
      might directly influence MEK activity to exhibit the antitumor metastatic
      activity in vitro. MEK kinase assay using myelin basic protein (MBP) revealed
      that TPA-augmented MEK activity in HT-1080 cells and that the augmented MEK
      activity was diminished by nobiletin treatment. In addition, the decrease in MEK
      activity caused by nobiletin was found to inhibit the phosphorylation of
      extracellular regulated kinases (ERK), a downstream signaling factor for MEK.
      Furthermore, when an immunoprecipitated active MEK was incubated with nobiletin
      under cell-free conditions, nobiletin was found to inhibit the MEK-mediated MBP
      phosphorylation. In contrast, other citrus polymethoxyflavonoids such as 3
      hydroxy-5,6,7,8,3',4'-hexamethoxyflavone (natsudaidain) and 3,5,6,7,8,3',4'
      heptamethoxyflavone, did not directly inhibit MEK activity. Moreover,
      natsudaidain and 3,5,6,7,8,3',4'-heptamethoxyflavone exhibited no or less
      inhibitory effect than nobiletin on the proMMP-9/progelatinase B production in HT
      1080 cells. Therefore, these results provide novel evidence that nobiletin
      directly inhibits MEK activity and decreases the sequential phosphorylation of
      ERK, exhibiting the antitumor metastatic activity by suppressing MMP expression
      in HT-1080 cells.

PMID- 18053807
TI  - Laboratory differentiation of Cushing's syndrome.
AB  - Cushing's syndrome (CS) is a complex of signs and symptoms due to chronic
      glucocorticoid excess from a variety of causes. Although CS is considered a rare
      disease, recent studies have suggested that it may be more frequent than
      previously expected in various clinical settings (i.e. subjects suffering from
      diabetes, osteoporosis or metabolic syndrome). If confirmed in large population
      based studies, more widespread screening for CS may be warranted. Missed
      diagnosis of CS may have detrimental consequences because hypercortisolism, even
      if not clinically apparent, increases the probability of future cardiovascular
      events through induction/amplification of several risk factors (hypertension,
      central adiposity, thrombophilic state, etc.). Identifying CS has represented one
      of the most challenging problems for the clinical endocrinologist since no test
      is 100% sensitive and specific. This review article will be focus on diagnostic
      laboratory procedures that support a rationale approach in the screening
      evaluation and in the differential diagnosis of the endogenous CS.
      Notwithstanding the difficulties derived from laboratory reliability and the
      adoption of a hormonal cut-off close to the sensitivity of many commercially
      available assays, an increasing amount of data have provided novel information
      aimed to meet the demand of inexpensive, convenient and reliable laboratory
      procedures.

PMID- 18053808
TI  - Distinct association of SLC19A1 polymorphism -43T>C with red cell folate levels
      and of MTHFR polymorphism 677C>T with plasma folate levels.
AB  - OBJECTIVES: The role of SLC19A1 -43T>C, MTHFR 677C>T and MS 2756A>G polymorphisms
      on red cell and plasma folate levels. DESIGN AND METHODS: Genotype analysis of
      the three polymorphisms. Red cell and plasma folate measurements in 64 patients
      with coronary artery disease. RESULTS: The non-wild type allele of SLC19A1
      polymorphism -43T>C was associated with low red cell folate levels and the non
      wild type allele of MTHFR polymorphism 677C>T with low plasma folate levels.
      CONCLUSION: SLC19A1 and MTHFR genes are differently associated with red cell and
      plasma folate levels.

PMID- 18053809
TI  - Poly(dG)-poly(dC) DNA appears shorter than poly(dA)-poly(dT) and possibly adopts
      an A-related conformation on a mica surface under ambient conditions.
AB  - Three types of DNA: approximately 2700 bp polydeoxyguanylic olydeoxycytidylic
      acid [poly(dG)-poly(dC)], approximately 2700 bp polydeoxyadenylic
      polydeoxythymidylic acid [poly(dA)-poly(dT)] and 2686 bp linear plasmid pUC19
      were deposited on a mica surface and imaged by atomic force microscopy. Contour
      length measurements show that the average length of poly(dG)-poly(dC) is
      approximately 30% shorter than that of poly(dA)-poly(dT) and the plasmid. This
      led us to suggest that individual poly(dG)-poly(dC) molecules are immobilized on
      mica under ambient conditions in a form which is likely related to the A-form of
      DNA in contrast to poly(dA)-poly(dT) and random sequence DNA which are
      immobilized in a form that is related to the DNA B-form.

PMID- 18053810
TI  - Characterization of a late gene, ORF67 from Bombyx mori nucleopolyhedrovirus.
AB  - Open reading frame 67 of Bombyx mori nucleopolyhedrovirus (BmORF67) is a
      homologue of Autographa californica multiple NPV ORF81. The gene is conserved
      among all baculoviruses and is thus considered a baculovirus core gene. The
      transcript of BmORF67 was detected at 18-72 h post-infection (p.i.). Polyclonal
      antiserum raised to a His-BmORF67 fusion protein recognized BmORF67 in infected
      cell lysates from 24 to 72 h p.i., suggesting that BmORF67 is a late gene.
      BmORF67 was not detected either in budded viruses or occlusion-derived virus.
      Immunofluoresence analysis showed that the protein located in the cytoplasm and
      interacted with host protein actin A3. In conclusion, BmORF67 is a late protein
      localized in the cytoplasm of infected cells that interacts with host protein.

PMID- 18053811
TI  - Dissection of the functional interaction between p53 and the embryonic proto
      oncoprotein PAX3.
AB  - Studies from murine embryogenesis and cancer cells derived from human melanomas
      have identified a critical role for the transcription factor PAX3 in the
      suppression of p53 protein accumulation and p53-dependent apoptosis. Here we
      show, using a well-defined over-expression system, that PAX3 suppresses p53
      dependent transcription from promoters of p53-responsive genes, notably BAX and
      HDM2-P2, and reduces p53 protein abundance by promoting its degradation. We
      define the functional domains of PAX3 required for this activity, and furthermore
      present evidence that PAX3-dependent inhibition of p53 is independent of binding
      of the N-terminal domain of p53 to HDM2, the primary negative regulator of
      cellular p53 activity.

PMID- 18053813
TI  - Cytostatic drugs differentially affect phenotypic features of porcine coronary
      artery smooth muscle cell populations.
AB  - We studied the effects of cytostatic drugs on porcine coronary artery spindle
      shaped (S) and rhomboid (R) smooth muscle cell (SMC) biological activities
      related to intimal thickening (IT) formation. Imatinib, and to a lesser extent
      curcumin, decreased proliferation of S- and R-SMCs and migratory and urokinase
      activities of R-SMCs more efficiently compared with cyclosporine plus rapamycin.
      Imatinib increased the expression of alpha-smooth muscle actin in both SMC
      populations and that of smoothelin in S-SMCs. It decreased S100A4 expression in R
      SMCs. By promoting SMC quiescence and differentiation imatinib and curcumin may
      represent valid candidates for restenosis preventive and therapeutic strategies.

PMID- 18053812
TI  - Inflammation and insulin resistance.
AB  - Obesity-induced chronic inflammation is a key component in the pathogenesis of
      insulin resistance and the Metabolic syndrome. In this review, we focus on the
      interconnection between obesity, inflammation and insulin resistance. Pro
      inflammatory cytokines can cause insulin resistance in adipose tissue, skeletal
      muscle and liver by inhibiting insulin signal transduction. The sources of
      cytokines in insulin resistant states are the insulin target tissue themselves,
      primarily fat and liver, but to a larger extent the activated tissue resident
      macrophages. While the initiating factors of this inflammatory response remain to
      be fully determined, chronic inflammation in these tissues could cause localized
      insulin resistance via autocrine/paracrine cytokine signaling and systemic
      insulin resistance via endocrine cytokine signaling all of which contribute to
      the abnormal metabolic state.

PMID- 18053814
TI  - The amino acids involved in the distinct carbohydrate specificities between
      macrophage galactose-type C-type lectins 1 and 2 (CD301a and b) of mice.
AB  - Binding specificities of mouse macrophage galactose-type C-type lectin 1
      (MGL1/CD301a) and 2 (MGL2/CD301b) toward various oligosaccharides were compared
      by frontal affinity chromatography. MGL1 preferentially bound oligosaccharides
      containing Lewis(X) (Le(X)) trisaccharides among 111 oligosaccharides tested,
      whereas MGL2 preferentially bound globoside Gb4. The important amino acids for
      the preferential bindings were investigated by pair-wise site-directed
      mutagenesis at positions 61, 89, 97, 100, 110-113, 115, 124, and 125 in the
      soluble recombinant carbohydrate recognition domains (CRD) prepared in
      Escherichia coli and purified with galactose-Sepharose. Mutations of Val, Ala,
      Thr, and Phe at positions 61, 89, 111 and 125 on MGL1 CRD caused reductions in
      Le(X) binding. Mutations of MGL2 CRD at Leu, Arg, Arg, and Tyr at positions 61,
      89, 115 and 125 were implicated in the preference for beta-GalNAc. Le(X) binding
      was observed with MGL2 mutants of Arg89Ala and Arg89Ala/Ser111Thr. MGL1 mutants
      of Ala89Arg and Ala89Arg/Pro115Arg showed beta-GalNAc bindings. Molecular
      modeling illustrated potential direct molecular interactions of Leu61, Arg89, and
      His109 in MGL2 CRD with GalNAc.

PMID- 18053815
TI  - Mitochondrial dysfunction is responsible for the intestinal calcium absorption
      inhibition induced by menadione.
AB  - Menadione (MEN) inhibits intestinal calcium absorption by a mechanism not
      completely understood. The aim of this work was to find out the role of
      mitochondria in this inhibitory mechanism. Hence, normal chicks treated with one
      i.p. dose of MEN were studied in comparison with controls. Intestinal calcium
      absorption was measured by the in situ ligated intestinal segment technique. GSH,
      oxidoreductase activities from the Krebs cycle and enzymes of the antioxidant
      system were measured in isolated mitochondria. Mitochondrial membrane potential
      was measured by a flow cytometer technique. DNA fragmentation and cytochrome c
      localization were determined by immunocytochemistry. Data indicate that in 30
      min, MEN decreases intestinal Ca(2+) absorption, which returns to the control
      values after 10 h. GSH was only decreased for half an hour, while the activity of
      malate dehydrogenase and alpha-ketoglutarate dehydrogenase was diminished for 48
      h. Mn(2+)-superoxide dismutase activity was increased in 30 min, whereas the
      activity of catalase and glutathione peroxidase remained unaltered. DNA
      fragmentation and cytochrome c release were maximal in 30 min, but were recovered
      after 15 h. In conclusion, MEN inhibits intestinal Ca(2+) absorption by
      mitochondrial dysfunction as revealed by GSH depletion and alteration of the
      permeability triggering the release of cytochrome c and DNA fragmentation.

PMID- 18053816
TI  - Different patterns of in vivo pro-oxidant states in a set of cancer- or aging
      related genetic diseases.
AB  - A comparative evaluation is reported of pro-oxidant states in 82 patients with
      ataxia telangectasia (AT), Bloom syndrome (BS), Down syndrome (DS), Fanconi
      anemia (FA), Werner syndrome (WS), and xeroderma pigmentosum (XP) vs 98 control
      donors. These disorders display cancer proneness, and/or early aging, and/or
      other clinical features. The measured analytes were: (a) leukocyte and urinary 8
      hydroxy-2'-deoxyguanosine (8-OHdG), (b) blood glutathione (GSSG and GSH), (c)
      plasma glyoxal (Glx) and methylglyoxal (MGlx), and (d) some plasma antioxidants
      [uric acid (UA) and ascorbic acid (AA)]. Leukocyte 8-OHdG levels ranked as
      follows: WS>BS approximately FA approximately XP>DS approximately AT
      approximately controls. Urinary 8-OHdG levels were significantly increased in a
      total of 22 patients with BS, FA, or XP vs 47 controls. The GSSG:GSH ratio was
      significantly increased in patients with WS and in young (< or =15 years)
      patients with DS or with FA and decreased in older patients with DS or FA and in
      AT, BS, and XP patients. The plasma levels of Glx and/or MGlx were significantly
      increased in patients with WS, FA, and DS. The UA and AA levels were
      significantly increased in WS and DS patients, but not in AT, FA, BS, nor XP
      patients. Rationale for chemoprevention trials is discussed.

PMID- 18053817
TI  - Muscle wasting in diabetic and in tumor-bearing rats: role of oxidative stress.
AB  - Cachexia is a debilitating syndrome characterized by body weight loss, muscle
      wasting, and anemia. Muscle wasting results from an altered balance between
      protein synthesis and degradation rates. Reactive oxygen species are indicated as
      crucial players in the onset of muscle protein hypercatabolism by upregulating
      elements of the ubiquitin-proteasome pathway. The present study has been aimed at
      evaluating comparatively the involvement of oxidative stress in the pathogenesis
      of skeletal muscle wasting in two different experimental models: rats rendered
      hyperglycemic by treatment with streptozotocin and rats bearing the Yoshida AH
      130 ascites hepatoma. For this purpose, both tumor bearers and diabetic animals
      have been treated with dehydroepiandrosterone (DHEA), a multifunctional steroid
      endowed with multitargeted antioxidant properties. We show that diabetic rats and
      AH-130 rats share several features, hypoinsulinemia, occurrence of oxidative
      stress, and positive response to DHEA administration, although the extent of the
      effects of DHEA largely differs between diabetic animals and tumor-bearing rats.
      The hypercatabolism, evaluated in terms of proteasome activity and expression of
      atrogin-1 and MuRF1, is activated in AH-130 rats, whereas it is lacking in
      streptozotocin-treated rats. Moreover, we demonstrate that the role of oxidative
      stress can interfere with muscle wasting through different mechanisms, not
      necessarily involving NF-kappaB activation. In conclusion, the present results
      show that, although skeletal muscle wasting occurs in both diabetic rats and
      tumor-host rats, the underlying mechanisms are different. Moreover, despite
      oxidative stress being detectable in both experimental models, its contribution
      to muscle wasting is not comparable.

PMID- 18053818
TI  - Redox-cycling compounds can cause the permeabilization of mitochondrial membranes
      by mechanisms other than ROS production.
AB  - The participation of reactive oxygen species (ROS) in the regulation of
      mitochondrial permeability transition pore (mPTP) opening by the redox-cycling
      compounds menadione and lucigenin was explored. The level of ROS was modulated by
      antioxidants, anoxia, and switching the sites of the reduction of redox cyclers,
      the dehydrogenases of the inner and outer mitochondrial membranes. We found that
      the reduction of both lucigenin and menadione in the outer mitochondrial membrane
      caused a strong production of ROS. However, mPTP opening was accelerated only in
      the presence of the cationic acceptor lucigenin. The antioxidants and scavengers
      of ROS that considerably decreased the level of ROS in mitochondria did not
      prevent or delay the mPTP opening. If the transmembrane potential under anoxia
      was supported by exogenous ATP or ferricyanide, the permeabilization of
      mitochondrial membranes by menadione or lucigenin was the same as under normoxia
      or even more pronounced. Under anoxia, the lucigenin-dependent permeabilization
      of membranes was less sensitive to mPTP antagonists than under normoxia. We
      conclude that the opening of the mPTP by redox cyclers may be independent of ROS
      and is due to the direct oxidation of mitochondrial pyridine nucleotides by
      menadione and the modification of critical thiols of the mPTP by the cation
      radical of lucigenin.

PMID- 18053819
TI  - Structural basis for the remarkable stability of Bacillus subtilis lipase (Lip A)
      at low pH.
AB  - Understanding the structural basis of altered properties of proteins due to
      changes in temperature or pH provides useful insights in designing proteins with
      improved stability. Here we report the basis for the pH-dependent thermostability
      of the Bacillus subtilis lipase (Lip A) using spectroscopic and X-ray
      crystallographic studies. At pH values above 7, lipase denatures and aggregates
      when heated at temperatures above 45 degrees C. However, at pH below 6 lipase
      denatures upon heating but the activity and its native structure is completely
      recovered upon cooling. In order to obtain the structural basis of this unusual
      stability of lipase, we determined high-resolution crystal structures of the
      lipase in two different crystal forms at pH 4.5 and 5. These structures show
      linear oligomerization of lipase using only two types of dimeric associations and
      these inter-molecular interactions are completely absent in several crystal forms
      of wild-type and mutant proteins obtained at basic pH. In accordance with the
      crystallographic studies, spectroscopic investigations reveal an invariant
      secondary structure in the pH range of 4-10. Quaternary organization of lipase at
      low pH resulted in changes in the tryptophan environment and binding of 1-anilino
      8-naphthalene sulfate (ANS) at low pH. Low pH stability of the lipase is not
      observed in the presence of sodium chloride (>0.2 M) indicating the importance of
      ionic interactions at low pH. Inter- and intra-molecular ionic interactions that
      occur at pH below 6.0 are proposed to trap the molecule in a conformation that
      allows its complete refolding upon cooling.

PMID- 18053820
TI  - Letter from the editor: children are not little adults.

PMID- 18053821
TI  - Letter from the guest editor.

PMID- 18053822
TI  - Case of the season: primary epiploic appendagitis: radiological diagnosis can
      avoid surgery.

PMID- 18053823
TI  - Malrotation.

PMID- 18053824
TI  - Intussusception in children: imaging choices.

PMID- 18053825
TI  - Imaging of appendicitis in children and adolescents: useful or useless? A
      comparison of imaging techniques and a critical review of the current literature.

PMID- 18053826
TI  - Inflammatory bowel disease: imaging of the pediatric patient.

PMID- 18053827
TI  - Imaging hepatobiliary disease in children.

PMID- 18053828
TI  - Imaging pediatric abdominal tumors.

PMID- 18053829
TI  - Pediatric abdominal magnetic resonance angiography.

PMID- 18053830
TI  - Imaging in pediatric blunt abdominal trauma.

PMID- 18053833
TI  - Pathophysiology of chronic pancreatitis.
AB  - Although the most common causes of chronic pancreatitis have not changed, it has
      become clear that a host of modifying biochemical, inflammatory, neural, and
      genetic deviations allows the disease to progress. Alterations in biochemical
      composition allow calcific stone formation, whereas various toxins, cytokines,
      and neuropeptides contribute to the progression of fibrosis and pain production.
      The basic cellular structure contributing to fibrosis of the pancreas has been
      elucidated and factors responsible for its activation delineated. Of most
      importance is the recent recognition of a set of genetic mutations that results
      in several aberrations of normal pancreatic physiology, which, in conjunction
      with other inciting insults or by themselves, allow the disease to begin and
      progress.

PMID- 18053834
TI  - The inflammatory cascade in acute pancreatitis: relevance to clinical disease.
AB  - Acute pancreatitis is an inflammatory condition that is initiated by the intra
      pancreatic activation of proteases. Pancreatic enzyme activation triggers a local
      and systemic inflammatory response that is associated with recruitment of
      inflammatory cells into the pancreas and a widespread up-regulation of
      inflammatory markers in distant tissues.

PMID- 18053835
TI  - Radiologic assessment of acute and chronic pancreatitis.
AB  - The capabilities of various imaging modalities, including CT, MRI, and
      ultrasound, have markedly increased over recent years. This has translated into
      improved detection and improved characterization of various pathologic processes.
      This article discusses the current role of imaging in the evaluation of acute and
      chronic pancreatitis. CT remains a major focal point in issues related to acute
      pancreatitis, whereas MRI (and magnetic resonance cholangiopancreatography) plays
      a larger role in chronic pancreatitis.

PMID- 18053836
TI  - Benign pancreatic tumors.
AB  - The goal of this article is to describe the different types of benign pancreatic
      neoplasms, methods to distinguish between them, and treatment options. Pancreatic
      adenocarcinoma is associated with specific neoplastic lesions that are similar in
      radiographic appearance to some benign lesions. The correct differentiation of
      these malignant and premalignant lesions from their benign counterpart is
      paramount to their proper management.

PMID- 18053837
TI  - Endoscopic management of acute and chronic pancreatitis.
AB  - Endoscopic therapy has been increasingly recognized as the effective therapy in
      selected patients with acute pancreatitis and chronic pancreatitis (CP). Utility
      of endotherapy in various conditions occurring in acute pancreatitis and CP is
      discussed. Its efficacy, limitations, and alternatives are addressed. For the
      best management of these complex entities, a multidisciplinary approach involving
      expertise in all pancreatic specialties is essential to achieve the goal.

PMID- 18053838
TI  - Nutrition support in pancreatitis.
AB  - Nutrition support is especially important in patients who have pancreatitis, as
      these patients have high metabolic needs and are usually unable to ingest
      sufficient calories from an oral diet because of pain or intestinal dysfunction.
      Clinicians must assess severity of the disease carefully, as initiation and
      timing of nutrition support are crucial. Depending on the severity, early
      nutrition support may be unnecessary, while late support ultimately may lead to
      worse outcomes. Route of nutrition support also plays an important role in
      treatment. The clinician has many alternatives from which to choose, including
      enteral nutrition given nasogastrically or nasojejunally, or parenteral nutrition
      given through a central line. This article explores the role of nutrition support
      in the outcome of pancreatitis and provides guidelines to aid the clinician in
      caring for patients who have acute and chronic pancreatitis.

PMID- 18053839
TI  - Diagnosis and management of sphincter of Oddi dysfunction and pancreas divisum.
AB  - Sphincter of Oddi dysfunction and pancreas divisum are very distinct anatomic
      abnormalities, yet are diagnosed in similar clinical situations. While both
      entities are uncommon, they are most often discovered during the evaluation of
      postcholecystectomy syndrome, recurrent idiopathic pancreatitis, and biliary or
      pancreatic pain when first line studies are normal. Treatment consists of
      surgical sphincteroplasty or endoscopic sphincterotomy for both diagnoses, which
      result in reliable relief of symptoms for most sphincter of Oddi dysfunction
      patients but less predictable response in pancreas divisum.

PMID- 18053840
TI  - Necrotizing pancreatitis: diagnosis and management.
AB  - Necrotizing pancreatitis is a severe disease characterized by gland necrosis and
      a destructive systemic inflammatory response. Early management involves
      aggressive resuscitative and supportive measures. Outcomes are primarily
      determined by the presence of late secondary bacterial infection of the necrotic
      gland. Early empiric antibiotics and late surgical necrosectomy in the
      appropriate setting are the keys to managing these sick patients. With
      appropriate management, mortality can be minimized and long-term quality of life
      may be restored.

PMID- 18053841
TI  - Operative and nonoperative management of pancreatic pseudocysts.
AB  - The management of pancreatic pseudocysts has changed greatly over the last
      decade. As laparoscopic and endoscopic techniques continue to evolve, their use
      in the treatment of pseudocysts has gained acceptance, whereas the role of
      percutaneous drainage has become more limited. The literature on laparoscopic,
      endoscopic, and percutaneous management of pancreatic pseudocyst is reviewed here
      and, based on these data, a treatment algorithm is suggested.

PMID- 18053842
TI  - Resectional therapy for chronic pancreatitis.
AB  - The main indication for operation in the management of chronic pancreatitis is
      medically intractable pain. Other indications include biliary or pancreatic
      ductal obstruction (with or without pseudocyst formation), mass effect impinging
      on other organs or adversely affecting their function, or diagnostic insecurity
      regarding the possibility of periampullary or pancreatic neoplasms. This article
      describes the current state of affairs for resectional therapy for chronic
      inflammatory conditions of the pancreas.

PMID- 18053843
TI  - The role of total pancreatectomy and islet autotransplantation for chronic
      pancreatitis.
AB  - Total pancreatectomy and islet autotransplantation are done for chronic
      pancreatitis with intractable pain when other treatment measures have failed,
      allowing insulin secretory capacity to be preserved, minimizing or preventing
      diabetes, while at the same time removing the root cause of the pain. Since the
      first case in 1977, several series have been published. Pain relief is obtained
      in most patients, and insulin independence preserved long term in about a third,
      with another third having sufficient beta cell function so that the surgical
      diabetes is mild. Islet autotransplantation has been done with partial or total
      pancreatectomy for benign and premalignant conditions. Islet autotransplantation
      should be used more widely to preserve beta cell mass in major pancreatic
      resections.

PMID- 18053844
TI  - Management of internal and external pancreatic fistulas.
AB  - A pancreatic fistula is an uncommon and challenging problem for the general
      surgeon. Protean in presentation, the underlying pathophysiology of a pancreatic
      duct disruption is consistent. Several basic principles, when followed, simplify
      management. These tenets include medical stabilization and nutritional
      optimization, definition of the underlying duct disorder, and, finally,
      definitive management with or without surgery. With appropriate prompt care,
      patients can achieve good outcomes.

PMID- 18053845
TI  - The management of pancreatic trauma in the modern era.
AB  - Pancreatic trauma presents challenging diagnostic and therapeutic dilemmas to
      trauma surgeons. Injuries to the pancreas have been associated with reported
      morbidity rates approaching 45%. If treatment is delayed, these rates may
      increase to 60%. The integrity of the main pancreatic duct is the most important
      determinant of outcome after injury to the pancreas. Undiagnosed ductal
      disruptions produce secondary infections, fistulas, fluid collections, and
      prolonged stays in the intensive care unit and hospital. This article analyzes
      the epidemiology, diagnostic approaches, options for nonoperative and operative
      management, and outcome after blunt and penetrating pancreatic trauma.

PMID- 18053846
TI  - Testing limits on matte surface color perception in three-dimensional scenes with
      complex light fields.
AB  - We investigated limits on the human visual system's ability to discount
      directional variation in complex lights field when estimating Lambertian surface
      color. Directional variation in the light field was represented in the frequency
      domain using spherical harmonics. The bidirectional reflectance distribution
      function of a Lambertian surface acts as a low-pass filter on directional
      variation in the light field. Consequently, the visual system needs to discount
      only the low-pass component of the incident light corresponding to the first nine
      terms of a spherical harmonics expansion [Basri, R., Jacobs, D. (2001).
      Lambertian reflectance and linear subspaces. In: International Conference on
      Computer Vision II, pp. 383-390; Ramamoorthi, R., Hanrahan, P., (2001). An
      efficient representation for irradiance environment maps. SIGGRAPH 01. New York:
      ACM Press, pp. 497-500] to accurately estimate surface color. We test
      experimentally whether the visual system discounts directional variation in the
      light field up to this physical limit. Our results are consistent with the claim
      that the visual system can compensate for all of the complexity in the light
      field that affects the appearance of Lambertian surfaces.

PMID- 18053847
TI  - A spatio-temporal interaction on the apparent motion trace.
AB  - During the perception of apparent motion, activity along the apparent motion
      trace has been found in the primary visual cortex. It has been hypothesized that
      this activity interferes with stimuli presented on the apparent motion trace
      ("motion masking"). We investigated whether this perceptual interference varies
      with regard to the trajectory of a moving object token in a detection task. We
      found a general decrease of detectability of targets presented on the trace.
      Surprisingly, targets presented in time with the trajectory were detected
      significantly more often than targets which appeared out of time. We relate this
      finding to a spatio-temporally specific prediction of visual events along the
      apparent motion trace.

PMID- 18053849
TI  - Page mode reading with simulated scotomas: a modest effect of interline spacing
      on reading speed.
AB  - Crowding is thought to be one potent limiting factor of reading in peripheral
      vision. While several studies investigated how crowding between horizontally
      adjacent letters or words can influence eccentric reading, little attention has
      been paid to the influence of vertically adjacent lines of text. The goal of this
      study was to examine the dependence of page mode reading performance (speed and
      accuracy) on interline spacing. A gaze-contingent visual display was used to
      simulate a visual central scotoma while normally sighted observers read
      meaningful French sentences following MNREAD principles. The sensitivity of this
      new material to low-level factors was confirmed by showing strong effects of
      perceptual learning, print size and scotoma size on reading performance. In
      contrast, reading speed was only slightly modulated by interline spacing even for
      the largest range tested: a 26% gain for a 178% increase in spacing. This modest
      effect sharply contrasts with the dramatic influence of vertical word spacing
      found in a recent RSVP study. This discrepancy suggests either that vertical
      crowding is minimized when reading meaningful sentences, or that the interaction
      between crowding and other factors such as attention and/or visuo-motor control
      is dependent on the paradigm used to assess reading speed (page vs. RSVP mode).

PMID- 18053848
TI  - Visually-guided behavior of homonymous hemianopes in a naturalistic task.
AB  - The gaze behavior of homonymous hemianopes differs from that of visually intact
      observers when performing simple laboratory tasks. To test whether such
      compensatory behavior is also evident during naturalistic tasks, we analyzed the
      gaze patterns of three long-standing hemianopes and four visually intact controls
      while they assembled wooden models. No significant differences in task
      performance, saccade dynamics or spatial distribution of gaze were observed.
      Hemianopes made more look-ahead fixations than controls and their gaze sequences
      were less predictable. Thus hemianopes displayed none of the compensatory gaze
      strategies seen in laboratory tasks. Instead, their gaze patterns suggest greater
      updating of, and greater reliance on a spatial representation.

PMID- 18053850
TI  - Classification images reveal spatiotemporal contour interpolation.
AB  - Contour interpolation is the process whereby spatially separated object fragments
      (inducers) are connected on the basis of their contour relations. An important
      characteristic of interpolation between simultaneously presented inducers is that
      observers rely on interpolation regions to perform a discrimination task.
      However, it is unclear if the same property holds when inducers are separated in
      both space and time. To address this question of spatiotemporal interpolation, we
      had participants discriminate spatiotemporally presented "fat" and "thin" noise
      corrupted figures, when the figures were stationary (Experiment 1) or moving
      (Experiment 2), and when the connections across vertical gaps were either real,
      interpolated (illusory), or absent. Classification images from both experiments
      showed that noise regions near interpolated boundaries affect performance
      comparably to when real contours appear, but very little in the absence of
      interpolation. The classification images also revealed information about the time
      course of interpolation and suggested that contour interpolation between
      simultaneously visible inducers may be a special case of a more general
      spatiotemporal contour interpolation process.

PMID- 18053853
TI  - Snapshot of the world--9/2007.

PMID- 18053854
TI  - Surgical treatment of dumbbell-shaped neurinomas: report of an experience with 57
      cases in a single hospital.
AB  - BACKGROUND: Dumbbell-shaped trigeminal neurinomas are rare benign tumors with a
      controversy regarding their treatment and surgical approaches. We conducted an
      investigation on elucidating a strategy for the treatment of DSTNs. METHODS: One
      hundred thirty-seven patients with trigeminal neurinomas, accounting for 0.6% of
      all intracranial tumors and 3.8% of intracranial neurinomas, were screened out
      from the data bank on brain tumors in Hua Shan Hospital (Shanghai, China) from
      1978 to 2003. Among them, 57 patients with DSTNs were found without
      Recklinghausen disease and analyzed retrospectively. Patients were divided into 2
      groups. In the early group (1978-1984), a series of conventional intradural
      approaches were used, and in the latter group (1985-2003), an
      extradurotransdurotranstrigeminal pore approach with orbitozygomatic craniotomy
      was applied. After the tumor in the middle cranial fossa was resected, the tumor
      in the posterior fossa was resected via a suboccipital approach in the early
      group and through enlarged porus trigeminus without resection of the petrous apex
      in the latter group. RESULTS: There were 12 patients in the early group and 45
      patients (including 6 patients with recurrent tumors) in the latter group. The
      mean age was 37 years (range, 14-56 years) and 39 years (range, 12-72 years),
      respectively, in the early and latter groups. There was no predominance in sex in
      the 2 groups. The mean duration of clinical manifestations before admission were
      2.2 and 2 years, respectively, in the early and latter groups. Tumor size
      measured on MRI and/or CT were 30 to 40 mm in 4 (33%) cases from the early group
      and 14 (31%) cases from the latter group, 41 to 50 mm in 8 (67%) cases from the
      early group and 25 (56%) cases from the latter group, and more than 50 mm in 6
      (13%) cases from the latter group. There were 3 patients in the latter group with
      a tumor extending into the infratemporal fossa and pterygopalatine fossa. Total
      tumor resection was achieved in 42% (5/12) of the early group and 87% (39/45) of
      the latter group (chi(2) = 10.897, P < .001); incomplete tumor removal was done
      in 58% (7/12) of the early group and 13% (6/45) of the latter group. One patient
      in the early group died of brainstem injury postoperatively. There was no
      surgical mortality in the latter group. Cranial nerve morbidities were seen in
      80% of the early group and 41% of the latter group (chi(2) = 12.052, P < .01),
      when patients were discharged. Six months after operation, however, cranial nerve
      morbidities were seen in 55% of the early group and 18.6% of the latter group
      (chi(2) = 8.585, P < .01). A long-term follow-up study was available in 41 (75%)
      patients, with a period of 2 to 20 years (mean, 10 years). Karnofsky prognosis
      scale scores were at least 90 in 60% of the early group and 77% of the latter
      group and 70 to 80 in 40% of the early group and 23% of the latter group.
      Recurrent tumors occurred in 3 patients from the early group and were reoperated
      on. One patient with a recurrent tumor from the latter group underwent
      radiosurgery 5 years after the operation. CONCLUSION: The best treatment for
      large or giant DSTNs is microsurgery with extradurotransdurotranstrigeminal pore
      approach via single-stage skull-base craniotomy. It is not necessary to resect
      the petrous apex for removal of the tumor in the posterior fossa. Radiosurgery
      can be used for the residual or recurrent tumors.

PMID- 18053857
TI  - Targeted percutaneous transforaminal endoscopic diskectomy in 295 patients:
      comparison with results of microscopic diskectomy.
AB  - BACKGROUND: The aim of this study is to compare the clinical outcomes and
      complications after targeted PTED and conventional microscopic diskectomy for
      removing 1-level unilateral LDH and to evaluate the efficacy of PTED for the
      treatment of LDH. METHODS: The authors retrospectively examined 915 consecutive
      patients who underwent PTED (group A, 301 patients) and microscopic diskectomy
      (group B, 614 patients) for 1-level unilateral LDH. Patients who were treated
      with a diskectomy in the period from July 2003 to December 2004 were evaluated by
      telephone interview and institute visit. This assessment was performed at least
      18 months (range, 18-36 months) after their operation. The follow-up rate in
      groups A and B was 97.5% (295 patients) and 96.5% (607 patients), respectively.
      RESULTS: Good or excellent results were obtained in 84.7% and 85.0% of groups A
      and B (P = .92). The rates of recurrence were 6.44% and 6.75% in groups A and B
      (P > .05). Twenty-eight patients (14 cases of recurrence, 5 cases of incomplete
      removal, 5 cases of stenosis, 2 cases of diskogenic back pain, and 2 cases of
      diskitis) in group A and 38 patients (26 cases of recurrence, 6 cases of
      incomplete removal, 2 cases of stenosis, 2 cases of diskogenic back pain, 1 case
      of hematoma, and 1 case of diskitis) in group B underwent reoperation.
      CONCLUSIONS: Based on our results, the PTED can be a reasonable alternative to a
      conventional microscopic diskectomy for the treatment of patients with LDH,
      except for those in downward far-migrating cases beneath the pedicle of the lower
      vertebra or in cases involving L5-S1 with a high pelvis.

PMID- 18053855
TI  - Citicoline improves functional recovery, promotes nerve regeneration, and reduces
      postoperative scarring after peripheral nerve surgery in rats.
AB  - BACKGROUND: Citicoline has been shown to have beneficial effects in a variety of
      CNS injury models. The aim of this study was to test the effects of citicoline on
      nerve regeneration and scarring in a rat model of peripheral nerve surgery.
      METHODS: Seventy adult Sprague-Dawley rats underwent a surgical procedure
      involving right sciatic nerve section and epineural suturing. Rats were assigned
      to the control or experiment groups to receive a topical application of 0.4 mL of
      saline or 0.4 mL (100 micromol/L) of citicoline, respectively. Macroscopic,
      histological, functional, and electromyographic assessments of nerves were
      performed 4 to 12 weeks after surgery. RESULTS: In the control versus citicoline
      treated rats, SFI was -90 +/- 1 versus -84 +/- 1 (P < .001), -76 +/- 4 versus -61
      +/- 3 (P < .001), and -66 +/- 2 versus -46 +/- 3 (P < .001) at 4, 8, and 12 weeks
      after surgery, respectively. At 12 weeks after surgery, axon count and diameter
      were 16400 +/- 600 number/mm(2) and 5.47 +/- 0.25 microm versus 22250 +/- 660
      number/mm(2) (P < .001) and 6.65 +/- 0.28 microm (P < .01) in the control and
      citicoline-treated groups, respectively. In citicoline-treated rats,
      histomorphological axonal organization score at the repair site was (3.4 +/- 0.1)
      significantly better than that in controls (2.6 +/- 0.3) (P < .001). Peripheral
      nerve regeneration evaluated by EMG at 12 weeks after surgery showed
      significantly better results in the citicoline group (P < .05). Nerves treated
      with citicoline demonstrated reduced scarring at the repair site (P < .001).
      CONCLUSION: Our results demonstrate that citicoline promotes regeneration of
      peripheral nerves subjected to immediate section suturing type surgery and
      reduces postoperative scarring.

PMID- 18053858
TI  - Opioids.

PMID- 18053859
TI  - Airhead: intraparenchymal pneumocephalus after commercial air travel.
AB  - BACKGROUND: Commercial air travel either in the postoperative setting or after
      open skull fracture has the potential to place patients at unnecessary risk.
      Although the timing is not clearly known, it should be established that there is
      no persistent fistulous tract that could introduce additional intraparenchymal
      air. CASE DESCRIPTION: We present a case of a gentleman with dramatic
      pneumocephalus after commercial air travel. CONCLUSION: Because of the potential
      for serious and permanent injury that can result from a dramatic and sustained
      increase in intracranial pressure, air travel should be delayed until there is no
      evidence of a fistulous tract. We discuss some basic in-flight options and
      precautions should change in timing of travel not be possible.

PMID- 18053860
TI  - A case report of a family with 7 patients of the Von Hippel-Lindau disease.
AB  - BACKGROUND: This study presents a family with hereditary cerebellar
      hemangioblastomas, as manifestations of the VHLD. METHODS: In a 20-year period, 7
      members of a family, in 3 generations, developed symptoms of the VHLD with very
      high frequency and gene penetration. Six patients were operated for cerebellar
      hemangioblastomas. Two had previously undergone ventriculoperitoneal shunting.
      There were 2 patients who developed renal and pancreatic cysts, 3 patients
      retinal hemangioblastoma, and 2 others epididymic cysts. A spinal cord
      arteriovenous malformation appeared in 1 patient who also had medulla
      hemangioblastoma. RESULTS: All the patients had a satisfactory recovery after the
      operation. One patient now has diabetes mellitus and renal insufficiency. Another
      patient lost vision in the left eye due to a retinal hemangioblastoma.
      CONCLUSIONS: Although rare, VHLD must always be part of the differential
      diagnosis of a patient with cerebellar hemangioblastoma. Timely diagnosis of the
      syndrome is essential for manifestations such as renal carcinoma or retinal
      hemangioblastoma. Organs of first-degree relatives that may be a target of the
      disease must thoroughly be investigated, and these relatives should be frequently
      followed up for the rest of their lives. Surgical resection is the gold standard,
      with excellent results, for hemangioblastomas of the cerebellum.

PMID- 18053862
TI  - Histologic analysis of a human trigeminal nerve after failed stereotactic
      radiosurgery: case report.
AB  - BACKGROUND: Stereotactic radiosurgery is an accepted surgery to treat patients
      with medically intractable trigeminal neuralgia. However, little is known about
      the mechanism of pain relief after trigeminal neuralgia radiosurgery. We report
      the histologic findings of a human trigeminal nerve after failed radiosurgery for
      trigeminal neuralgia. CASE DESCRIPTION: A 74-year-old patient presented with a 10
      year history of refractory trigeminal neuralgia. Prior surgeries included an MVD
      and PRGR. Gamma knife radiosurgery was performed targeting the proximal
      trigeminal nerve using one 4-mm isocenter (maximum dose, 85 Gy). She experienced
      good pain relief (no pain, reduced medications) for 16 months. She had no new
      trigeminal deficits after this procedure. The pain recurred, and she underwent
      repeat gamma knife radiosurgery targeting the distal trigeminal nerve using one 4
      mm isocenter (maximum dose, 70 Gy). The pain continued to escalate until she
      required hospitalization for pain control and hydration. Three weeks after her
      second radiosurgical procedure, she underwent a repeat posterior fossa
      exploration. During that surgery, her trigeminal nerve was partially sectioned,
      and a small segment of the proximal to midcisternal nerve was sent for
      histological examination. There was no histologic evidence of nerve damage.
      CONCLUSION: This case supports the contention that trigeminal nerve injury is
      required to provide long lasting pain relief after trigeminal neuralgia
      radiosurgery.

PMID- 18053865
TI  - Jugular bulb venous thrombosis caused by mild head injury: a case report.
AB  - BACKGROUND: We present here the first report of a jugular bulb venous thrombosis
      after mild head injury, which lacked either a skull fracture or abnormal findings
      on CT scan. CASE DESCRIPTION: An 8-year-old boy was hit on the back of the head
      and experienced headache and vomiting beginning the next morning. A CT scan and
      cranial x-ray examination failed to reveal any abnormal findings. The patient was
      treated conservatively; however, his headache and vomiting persisted. At 13 days
      after the injury, he began to show double vision due to left VIth nerve palsy and
      bilateral papilloedemas, suggesting an increased ICP. Although repeated CT scan
      failed to detect abnormal findings in both the supra- and infra-tentorial
      regions, MRI clearly visualized a thrombus which was situated within the right
      jugular bulb. Furthermore, MRV demonstrated disruption of venous flow at the
      jugular bulb. The patient was administered heparin continuously. His symptoms
      improved and the CSF pressure on lumbar puncture returned to a normal level at 20
      days after admission. Magnetic resonance imaging showed resolution of the clot,
      and MRV appeared to demonstrate partial recanalization simultaneously. The
      patient was discharged without any neurologic deficits. The clot in the jugular
      bulb disappeared completely after 4 months, and he could be followed up for 1
      year. CONCLUSION: This case underscores the fact that MRI may represent the
      exclusive screening examination in cases of sinus thrombosis when it occurs
      within the jugular bulb, as CT scan fails to reveal any findings suggestive of
      venous thrombosis.

PMID- 18053867
TI  - Secondary cervical dystonia following stereotactic radiosurgery in a patient with
      thalamic glioma.
AB  - BACKGROUND: Cervical dystonia associated with structural lesion is uncommon. We
      report the first patient with secondary CD after stereotactic radiosurgery for
      thalamic glioma. Possible network abnormalities relevant to manifestation of CD
      were discussed. CASE DESCRIPTION: A 27-year-old woman complaining of headache and
      left motor weakness was found to have a thalamic tumor on the right side. The
      lesion was totally removed using transventricular approach. Histopathologically,
      tumor samples manifested features of anaplastic astrocytoma. She underwent
      stereotactic radiosurgery in addition to the conventional radiation and
      chemotherapy. Afterward, she returned to her usual life without any neurological
      deficits. Sixteen months postoperatively, the patient developed forced head
      tilting to the left side combined with chin lift. On the TWSTRS, she registered
      15 for torticollis severity. The abnormal head posturing was alleviated by the
      sensory trick of touching her face with her right hand. Irregular-shaped lesion
      involving the thalamus, lenticular nuclei, midbrain, pons, and cerebellum was
      presented on magnetic resonance images. Steroid therapy effectively diminished
      the lesion size, and her abnormal head posturing was gradually ameliorated
      (TWSTRS severity scale = 3). CONCLUSION: The clinical-neuroradiological course of
      the present case strongly suggested that the lesion detected long after the
      surgery was due to radiation necrosis. The present study may provide a critical
      information in understanding pathophysiological mechanisms of CD that may involve
      substantial interactions between olivocerebellar and basal ganglia
      thalamocortical circuits.

PMID- 18053868
TI  - Traumatic pseudoaneurysm of the middle meningeal artery: possible indicators for
      early diagnosis in the computed tomography era.
AB  - OBJECTIVE AND IMPORTANCE: Traumatic pseudoaneurysms of the middle meningeal
      artery, which are associated with high mortality, are difficult to detect early
      by CT. We provide serial CT scans to show the steps of their formation and
      suggest characteristics that could be useful in the detection. CLINICAL
      PRESENTATION: A 25-year-old man was initially in deep coma had an anisocoric
      pupil after a traffic accident. Brain CT showed basal skull fracture and
      traumatic subarachnoid hemorrhage with severe brain swelling. Emergent
      decompressive craniectomy was performed, and 2 days later, an EDH appeared at the
      left temporal fossa. Careful examination of the image revealed a hypodense nodule
      inside the acute hematoma. He underwent craniotomy to remove the hematoma. Serial
      CT of the residual hematoma showed the gradual development of an organized
      hematoma around the hypodense nodule. The nodule had low density, which was
      strongly enhanced on CT after injection of contrast medium. The nodule was highly
      suspected to be a vascular lesion. A middle meningeal artery pseudoaneurysm was
      discovered through a 3-dimensional computed tomographic angiography. He underwent
      another craniotomy to remove the pseudoaneurysm. INTERVENTION: The diagnostic
      approach was CT, 3-dimensional CT, and craniotomies. CONCLUSION: Four CT findings
      may be useful for early diagnosis: (1) basal skull fracture in the temporal
      region; (2) hypodense nodule within an acute hematoma; (3) hypodense nodule
      within an organized and encapsulated hematoma; and (4) strong and homogenous
      enhancement of the hypodense nodule within an organized and encapsulated
      hematoma. Three-dimensional computed tomographic angiography is an effective and
      noninvasive tool to confirm this diagnosis.

PMID- 18053871
TI  - To retire or not to retire, that is the question!

PMID- 18053873
TI  - Fallopian tube cancer: stepchild or mother?

PMID- 18053874
TI  - Neural compensation after early lesions: a clinical view of animal experiments.
AB  - The widely held view, known as Kennard's principle, that lesions in the human
      central nervous system in the perinatal period are followed by better
      compensation than equivalent lesions sustained at a later age is under challenge
      from results of animal experiments. Experiment in rats have demonstrated,
      contrastingly, that lesions at early stages generally lead to more behavioral
      impairments than lesions of a similar size and location at adult stages. It also
      has been demonstrated that early lesions often lead to extensive neural
      reorganizations. Certain experiments even indicated that the extent of these
      reorganizations (e.g., after lesions in the motor cortex or the cerebellum) is
      inversely related to the degree of behavioral compensation. The question arises,
      why there is a discrepancy between the results in the human, suggesting enhanced
      functional recovery after lesions at perinatal ages, and those from animal
      experiments? One explanation is that lesions in animal experiments often are much
      larger than those occurring in the human. Secondly, the timing of the insult
      relative to the brain development seems to be critical. For each neural system a
      specific relation seems to exist between the timing of the insult, the degree of
      the neuronal reorganization and the behavioral consequences. Results from
      experimental research have suggested that the recruitment of stem cells in the
      brain after early lesions in certain regions might play a role in the repair of
      lesioned areas and also, that stem cells might play a role in the rescue of
      compromised cells. Ultimately such therapies might help to alleviate the
      consequences of perinatal brain lesions in the human.

PMID- 18053875
TI  - Corticospinal tract development and its plasticity after perinatal injury.
AB  - The final pattern of the origin and termination of the corticospinal tract is
      shaped during development by the balance between projection and withdrawal of
      axons. In animals, unilateral inhibition of the sensorimotor cortex during
      development results in a sparse contralateral projection from this cortex and
      retention of a greater number of ipsilateral projections from the more active
      cortex. Similarly in subjects with hemiplegic cerebral palsy if transcranial
      magnetic stimulation (TMS) of the damaged motor cortex fails to evoke responses
      in the paretic upper limb, TMS of the undamaged ipsilateral motor cortex evokes
      abnormally large and short-onset responses. Rather than representing a
      "reparative plasticity in response to injury", this review presents evidence that
      increased ipsilateral projections from the non-infarcted motor cortex arise from
      perturbation of ongoing developmental processes, whereby reduced activity in the
      damaged hemisphere, leads to increased withdrawal of its surviving contralateral
      corticospinal projections because their terminals have been displaced by the more
      active ipsilateral projections of the undamaged hemisphere and thereby adding to
      the degree of long-term motor impairment.

PMID- 18053876
TI  - Near-complete migraine prophylaxis with amlodipine: a case report.

PMID- 18053877
TI  - Refractive surgery in children.

PMID- 18053879
TI  - Clinical effects of primary posterior continuous curvilinear capsulorhexis.

PMID- 18053880
TI  - Advantage and disadvantage of posterior continuous curvilinear capsulorhexis.

PMID- 18053882
TI  - Nomenclature to denote conventional phacoemulsification.

PMID- 18053883
TI  - Reducing the risk of endophthalmitis after cataract surgery.

PMID- 18053886
TI  - Combating endophthalmitis with microphakonit and no-anesthesia technique.

PMID- 18053888
TI  - Topical anesthesia and postoperative endophthalmitis.

PMID- 18053890
TI  - Cataract surgical problem.

PMID- 18053897
TI  - Chandelier retroillumination-assisted torsional oscillation for cataract surgery
      in patients with severe corneal opacity.
AB  - We describe a technique that uses 25-gauge transconjunctival chandelier
      endoillumination in combination with a torsional oscillation system for cataract
      surgery in cases with severe bullous keratopathy. Because of the hands-free and
      self-retaining nature of the chandelier fiber, continuous curvilinear
      capsulorhexis and subsequent bimanual intraocular manipulation can be performed
      easily. Torsional oscillation efficiently emulsifies lens particles along with
      the fluidics, preventing posterior capsule rupture and endothelial cell damage.
      After the chandelier fiber is removed at the end of surgery, the 25-gauge
      incision self-seals. This technique is safe and provides excellent visualization
      during cataract surgery in patients with severe corneal opacities.

PMID- 18053898
TI  - Intraocular lens roll-up technique: foldable IOL implantation using forceps
      through incisions smaller than 3.2 mm.
AB  - We describe the intraocular lens (IOL) roll-up technique, which uses lens forceps
      to insert 3 types of foldable polyacrylic IOLs with optic diameters of 6.0 mm
      through small sclerocorneal incisions comparable to those used by injector
      systems.

PMID- 18053899
TI  - Laser-assisted subepithelial keratectomy for anisometropic amblyopia in children:
      outcomes at 1 year.
AB  - PURPOSE: To assess the refractive, visual acuity, and binocular results of laser
      assisted subepithelial keratectomy (LASEK) for anisomyopia, anisohyperopia, and
      anisoastigmatia in children with various levels of amblyopia secondary to the
      anisometropic causes. SETTING: Nonhospital surgical facility with follow-up in a
      hospital clinic setting. METHODS: This retrospective review was of 53 children
      with anisometropia who had LASEK to correct the refractive difference between
      eyes. All LASEK procedures were performed using general anesthesia. Patients were
      divided into 3 groups according to their anisometropia as follows: myopic
      difference greater than 3.00 diopters (D), astigmatic difference greater than
      1.50 D, and hyperopic difference greater than 3.50 D. The children were followed
      for at least 1 year, and their refractive status, visual acuity, and binocular
      vision were assessed and recorded at 2 and 6 months as well as 1 year. RESULTS:
      The mean age at treatment was 8.4 years (range 10 months to 16 years). The mean
      preoperative anisometropic difference was 6.98 D in the entire group, 9.48 D in
      the anisomyopic group, 3.13 D in the anisoastigmatic group, and 5.50 D in the
      anisohyperopic group. One year after LASEK, the mean anisometropic difference
      decreased to 1.81 D, 2.43 D, 0.74 D, and 2.33 D, respectively, and 54% of all
      eyes were within +/-1.00 D of the fellow eye, 68% were within +/-2.00 D, and 80%
      were within +/-3.00 D. Preoperative visual acuity and binocular vision could be
      measured in 33 children. Postoperatively, 63.6% of children had an improvement in
      best corrected visual acuity (BCVA) and the remainder had no noted change. No
      patient had a reduction in BCVA or a loss in fusional ability after LASEK. Of the
      33 children, 39.4% had positive stereopsis preoperatively and 87.9% had positive
      stereopsis 1 year after LASEK. CONCLUSION: Laser-assisted subepithelial
      keratectomy is an effective surgical alternative to improve visual acuity in
      anisometropic children unable to tolerate conventional methods of treatment or in
      whom these methods fail.

PMID- 18053900
TI  - Corneal collagen crosslinking with riboflavin and ultraviolet A to treat induced
      keratectasia after laser in situ keratomileusis.
AB  - PURPOSE: To determine whether riboflavin and ultraviolet-A (UVA) corneal
      crosslinking can be used as an alternative therapy to prevent the progression of
      keratectasia. SETTING: Institute for Refractive and Ophthalmic Surgery, Zurich,
      Switzerland, and a private clinic, Athens, Greece. METHODS: Corneal crosslinking
      was performed in 10 patients with formerly undiagnosed forme fruste keratoconus
      or pellucid marginal corneal degeneration who had laser in situ keratomileusis
      (LASIK) for myopic astigmatism and subsequently developed iatrogenic
      keratectasia. Surgery was performed in 1 eye per patient. RESULTS: Crosslinking
      induced by riboflavin and UVA arrested and/or partially reversed keratectasia
      over a postoperative follow-up of up to 25 months as demonstrated by preoperative
      and postoperative corneal topography and a reduction in maximum keratometric
      readings. CONCLUSION: Riboflavin-UVA corneal crosslinking increased the
      biomechanical stability of the cornea and may thus be a therapeutic means to
      arrest and partially reverse the progression of LASIK-induced iatrogenic
      keratectasia.

PMID- 18053901
TI  - Laser in situ keratomileusis versus surface ablation: visual outcomes and
      complications.
AB  - PURPOSE: To compare the visual outcomes and complications of laser in situ
      keratomileusis (LASIK) with those of surface treatment by laser-assisted
      subepithelial keratectomy (LASEK), photorefractive keratectomy with mechanical
      epithelial removal (M-PRK), and transepithelial photorefractive keratectomy (T
      PRK). SETTING: Tertiary care eye center. METHODS: This retrospective review
      comprised all cases of LASIK, LASEK, M-PRK, and T-PRK performed at King Khaled
      Eye Specialist Hospital between July 1, 2004, and June 30, 2005. Separate
      statistical analyses were performed for eyes with low to moderate myopia
      (spherical equivalent [SE] less than -6.00 diopters [D]) and high myopia (SE 
      6.00 to -11.25 D). RESULTS: Of 696 eyes that met the inclusion criteria, 464 had
      LASIK, 104 had LASEK, 69 had M-PRK, and 59 had T-PRK. Eyes with low to moderate
      myopia had a statistically significantly smaller mean difference between logMAR
      final postoperative uncorrected visual acuity (UCVA) and preoperative best
      spectacle-corrected visual acuity (BSCVA) after T-PRK and M-PRK than after LASIK
      or LASEK. A higher percentage of eyes with high myopia had a final UCVA within +/
      2 lines of the preoperative BSCVA with T-PRK than with LASIK, LASEK, or M-PRK.
      There were more major non-flap-related complications after LASEK than after
      LASIK, M-PRK, or T-PRK. CONCLUSIONS: In eyes with low to moderate myopia, T-PRK
      and M-PRK provided slightly better visual outcomes than LASIK or LASEK. In eyes
      with high myopia, T-PRK provided better visual outcomes than LASIK, LASEK, and M
      PRK. Laser in situ keratomileusis was associated with the most major
      postoperative complications.

PMID- 18053902
TI  - Comparison of corneal flap thickness between primary eyes and fellow eyes using
      the Zyoptix XP microkeratome.
AB  - PURPOSE: To evaluate corneal flap thickness created in myopic laser in situ
      keratomileusis (LASIK) using the Zyoptix XP 120 microkeratome (Bausch & Lomb).
      SETTING: University-based eye clinic. METHODS: Corneal thickness was measured
      preoperatively and intraoperatively after flap creation in 62 consecutive
      patients (124 eyes) who had LASIK for the correction of myopia. Corneal flap
      thickness was calculated by subtracting stromal bed thickness from total corneal
      thickness. In each patient, both corneas (right followed by left) were cut by 1
      the same Zyoptix XP 120 microkeratome blade at the same session. RESULTS: The
      mean actual flap thickness was 115.34 microm +/- 16.34 (SD) in right eyes and
      104.55 +/- 14.34 mum in left eyes. The mean actual flap thickness in right eyes
      was not statistically significantly different from the 120 microm proposed by the
      manufacturer (P = .142); however, the mean actual flap thickness in left eyes was
      statistically significantly different from the 120 microm (P<.001). The mean flap
      thickness in the second eye was also statistically significantly thinner than in
      the first eye (P<.001). CONCLUSIONS: The corneal flaps were thinner than expected
      when a Zyoptix XP 120 microkeratome was used in LASIK. Although the first cuts
      produced thinner flaps, this difference was not statistically significant.
      However, the second cuts produced significantly thinner flaps.

PMID- 18053903
TI  - Change in the accommodative convergence per unit of accommodation ratio after
      bilateral laser in situ keratomileusis for myopia in orthotropic patients:
      prospective evaluation.
AB  - PURPOSE: To analyze the effect of bilateral laser in situ keratomileusis (LASIK)
      on the accommodative convergence per unit of accommodation (AC/A) ratio in
      otherwise normal orthotropic myopic patients. SETTING: Cornea and refractive
      services of a tertiary-care ophthalmic center. METHODS: This prospective clinical
      trial consisted of 61 myopic patients who had bilateral LASIK. Those with
      manifest tropia, previous squint surgery, amblyopia, or absent or impaired
      binocularity or those in whom monovision was planned were excluded. The
      preoperative examination included visual acuity, cycloplegic refraction,
      assessment of binocularity, a prism cover test, and evaluation of the stimulus
      AC/A ratio by the gradient method. All patients had LASIK using the Zyoptix
      platform (Bausch & Lomb). Postoperative evaluation included uncorrected and best
      corrected visual acuities, residual refraction, and the AC/A ratio. RESULTS: All
      patients had a follow-up of 9 months. There was significant decrease in the mean
      AC/A ratio at the 1-week and 1-month follow-ups. The AC/A progressively recovered
      to near preoperative values between 3 months and 9 months after surgery (analysis
      of variance test). There was a significant reduction in the number of symptomatic
      patients from the first month onward (chi square = 89.23; P<.001). CONCLUSIONS:
      The AC/A ratio varied after LASIK, stabilizing between 3 months and 9 months
      after surgery. This suggests that the maximum variation in the accommodation
      convergence relationship after LASIK occurs in the first 3 months.

PMID- 18053904
TI  - Functional vision with bilateral ReZoom and ReSTOR intraocular lenses 6 months
      after cataract surgery.
AB  - PURPOSE: To compare the visual outcomes in patients with bilateral implantation
      of AcrySof ReSTOR multifocal intraocular lenses (IOLs) (Alcon Laboratories) or
      ReZoom multifocal IOLs (Advanced Medical Optics) 6 months after cataract surgery.
      SETTING: Orsett and Southend Hospital, Essex, United Kingdom. METHODS: This study
      comprised patients who had uneventful bilateral cataract extraction with
      implantation of ReZoom (n = 50) or ReSTOR (n = 50) multifocal IOLs. Parameters
      analyzed included binocular uncorrected distance, intermediate, and near
      acuities; spectacle independence; subjective visual symptoms; and patient
      satisfaction. All parameters were evaluated 6 months after second-eye surgery.
      RESULTS: All patients had binocular uncorrected distance visual acuity of 20/32
      or better; there was no statistically significant difference between the 2
      groups. The mean binocular uncorrected near acuity was 20/26 (J1.22) in the
      ReSTOR group and 20/34 (J2.34) in the ReZoom group (P<.0001). The mean binocular
      uncorrected intermediate visual acuity was 20/42 and 20/34, respectively (P =
      .003). Patients in the ReZoom group reported greater satisfaction with
      intermediate vision (P = .04). No statistically significant difference was found
      in satisfaction with near vision. Eighty-six percent of ReSTOR patients and 70%
      of ReZoom patients did not wear glasses for daily activities; the overall
      satisfaction was not statistically significantly different between groups. There
      was no significant difference between groups in photic phenomena. CONCLUSIONS:
      The ReSTOR IOL provided better near vision and the ReZoom IOL better intermediate
      vision. Both multifocal IOLs gave excellent distance vision. Photic phenomena
      were comparable and clinically acceptable. ReSTOR patients had greater spectacle
      independence for near vision and ReZoom patients for intermediate vision. Overall
      spectacle independence was not statistically significantly different.

PMID- 18053905
TI  - Influence of the signal-to-noise ratio on the accuracy of IOLMaster measurements.
AB  - PURPOSE: To evaluate the relationship between the sound-to-noise ratio (SNR) and
      the reliability of axial length (AL) measurements obtained with the IOLMaster
      (Carl Zeiss Meditec AG). SETTING: Department of Ophthalmology, Saiseikai
      Kurihashi Hospital, Saitama, Japan. METHODS: In a clinical prospective study, 216
      consecutive eyes of 144 patients scheduled for cataract surgery were evaluated
      for the type and severity of cataract using the Lens Opacities Classification
      System III. Preoperative and postoperative AL measurements were performed with
      the IOLMaster. The preoperative SNR values were used to divide the eyes into 5
      groups. The following were compared between the groups: preoperative logMAR best
      spectacle-corrected visual acuity (BSCVA), difference in AL between
      preoperatively and postoperatively, error in the postoperative predicted
      refraction, and type and severity of cataract. RESULTS: The preoperative logMAR
      BSCVA was significantly worse in eyes with an SNR <2 (P<.05). The AL was longer
      preoperatively than postoperatively in all groups, and there was a significant
      difference in the <2 SNR group and the 2 to <5 group (P<.05). There were no
      significant differences in the error in postoperative predicted refraction. The
      percentage of patients with P4 or worse posterior subcapsular cataract (PSC)
      increased significantly with a decrease in the SNR (P<.01). However, there was no
      correlation between nuclear color grade and the SNR. CONCLUSION: The SNR value
      was useful in confirming the good quality of AL readings taken with the
      IOLMaster, even though the SNR value correlated significantly with the
      preoperative logMAR BSCVA and PSC severity.

PMID- 18053906
TI  - Primary piggyback implantation using the Tecnis ZM900 multifocal intraocular
      lens: case series.
AB  - PURPOSE: To assess the postoperative outcomes of primary piggyback implantation
      using the Tecnis ZM900 multifocal intraocular lens (IOL) (Advanced Medical
      Optics). SETTING: Hospital Oftalmologico de Brasilia, Brasilia, Brazil. METHODS:
      Patients who had phacoemulsification with primary piggyback IOL implantation were
      analyzed prospectively. In all cases, a Tecnis ZM900 multifocal IOL was implanted
      in the capsular bag and a second silicone IOL was implanted in the ciliary
      sulcus. Information collected included near and distance uncorrected visual
      acuity (UCVA), best corrected visual acuity (BCVA), and the spherical equivalent
      (SE) before and after the surgery. RESULTS: Twenty eyes of 12 patients were
      included in the study. They were followed for 6 months. The mean preoperative
      distance UCVA was 20/400. At the last follow-up (6 months), the mean distance
      UCVA was 20/29, significantly better than before referral (P<.001). The mean
      preoperative SE was +6.35 diopters (D) +/- 2.25 (SD). Six months after surgery,
      the mean SE was -0.25 +/- 0.40 D (range -1.00 to +0.50 D), significantly better
      than before referral (P<.001). No patient lost lines of BCVA after surgery. At
      the last follow-up, 90% of the eyes achieved a near UCVA of J1 and 83.3% of
      patients were spectacle independent for near and distance vision. A second
      refractive procedure was performed in 2 eyes. CONCLUSIONS: Primary piggyback
      implantation using the Tecnis ZM900 multifocal IOL was a simple, safe, and
      accurate option for patients with high hyperopia who wanted to reduce their
      dependency on spectacles.

PMID- 18053907
TI  - Meridional analysis for calculating the expected spherocylindrical refraction in
      eyes with toric intraocular lenses.
AB  - PURPOSE: To present a method of calculating the expected spherocylindrical
      refraction after toric intraocular lens (IOL) implantation and to compare it with
      the actual outcomes in a small group of patients. SETTING: Eye Institute, Tan
      Tock Seng Hospital, Singapore. METHODS: The expected refractions of the 2
      principal meridians of the cornea (maximum keratometry and minimum keratometry)
      were calculated separately using the Holladay 1 formula with a modification to
      the data used for the effective lens position. The expected refraction was
      compared with the actual outcomes in 7 eyes that had phacoemulsification with
      toric IOL implantation. RESULTS: The mean preoperative keratometric cylinder was
      2.07 diopters (D) +/- 0.97 (SD) (range 1.25 to 3.75 D), and the mean
      postoperative cylinder by subjective refraction was 0.68 +/- 0.40 D (range 0.25
      to 1.50 D). The mean expected cylindrical refraction was 0.62 +/- 0.46 D (range
      0.30 to 1.60 D). Five eyes (71.4%) were within +/-0.25 D of the expected
      refraction, and all eyes were within +/-0.50 D. There was a significant reduction
      in cylinder after toric IOL implantation (P<.001, paired t test). There was no
      statistically significant difference between the magnitude of the expected
      cylindrical refraction and the actual postoperative cylinder by subjective
      refraction (P = .604). CONCLUSION: Calculation of the expected spherocylindrical
      refraction with toric IOLs was achieved using meridional analysis.

PMID- 18053908
TI  - Functional evaluation of corneal endothelium by combined measurement of corneal
      volume alteration and cell density after phacoemulsification.
AB  - PURPOSE: To assess a new method of functional evaluation of corneal endothelium
      using combined measurement of corneal volume alteration and cell density (CD)
      after phacoemulsification. SETTING: Nippon Medical School Hospital, Tokyo, Japan.
      METHODS: Phacoemulsification was performed in 28 cases. The corneal volume within
      3.0 mm and 10.0 mm circles of the cornea was measured using Scheimpflug imaging
      (Pentacam, Oculus, Inc.) and the cell density, using specular microscopy (Noncon
      Robo, Konan Medical). The volume stress index (VSI), a parameter for measuring
      functional evaluation, was calculated by dividing the volume increase within the
      3.0 mm circle (preoperative corneal volume - corneal volume at time of
      measurement) by the central cell density value. The resulting value is indicative
      of the amount of postoperative increase in corneal volume with which each corneal
      endothelial cell should be able to cope. RESULTS: Three months after surgery, the
      3.0 mm corneal volume returned to preoperative values, while the 10.0 mm corneal
      volume remained significantly higher than preoperatively. The cell density values
      did not significantly change throughout the study. The VSI showed a significant
      decrease by 7 days after surgery followed by a gradual decrease until the end of
      the study. At 3 months, the VSI value was significantly smaller than at 1 day.
      CONCLUSION: The corneal volume increase after surgery may be indicative of the
      degree of the endothelial damage in the area; thus, the VSI may be useful in the
      functional assessment of the corneal endothelium.

PMID- 18053909
TI  - Distribution and visual impact of postoperative refractive error after cataract
      surgery in rural China: study of cataract outcomes and up-take of services report
      4.
AB  - PURPOSE: To model the possible impact of using average-power intraocular lenses
      (IOLs) and evaluate the postoperative refractive error in patients having
      cataract surgery in rural China. SETTING: Rural Guangdong, China. METHODS:
      Patients having cataract surgery by local surgeons were examined and visual
      function was assessed 10 to 14 months after surgery. Subjective refraction at
      near and distance was performed bilaterally by an ophthalmologist. Patients had a
      target refraction of -0.50 diopter (D) based on ocular biometry. RESULTS: Of the
      313 eligible patients, 242 (77%) could be contacted and 176 (74% of contacted
      patients, 56% overall) were examined. Examined patients had a mean age of 69.4 +/
      10.5 years. Of the 211 operated eyes, 73.2% were within +/-1.0 D of the target
      refraction after surgery. The best presenting distance vision was in patients
      within +/-1.0 D of plano and the best presenting near vision, in those with mild
      myopia (<-1.0 D to > or =2.0 D) (P= .005). However, patients with hyperopia
      (>+1.0 D) reported significantly better adjusted visual function than those with
      emmetropia or myopia (<-1.0 D). When the predicted use of an average-power IOL
      (median +21.5 D) was modeled, predicted visual acuity was significantly reduced
      (P= .001); however, predicted visual function was not significantly altered
      (P>.3). CONCLUSIONS: Accurate selection of postoperative refractive error was
      achieved by local surgeons in this rural area. Based on visual function results,
      aiming for mild postoperative myopia may not be suitable in this setting.
      Implanting average-power IOLs significantly reduced postoperative presenting
      vision, but not visual function.

PMID- 18053910
TI  - Accuracy of surrogate decision making in elective surgery.
AB  - PURPOSE: To assess the accuracy of surrogate decision making for elective
      cataract surgery. SETTING: Comprehensive Ophthalmology Department of Tertiary
      Care Hospital. METHODS: Decisions regarding elective cataract surgery of
      currently competent, elderly patients were compared with the predictions of
      patient-identified surrogate decision makers in scenarios of current state of
      mental health and progressive dementia. Patients were identified (age >50 years,
      Mini-Mental Status Score >20, absence of significant noncataract pathology)
      consecutively at a scheduled clinic visit to a single provider. Preferences for
      cataract surgery in the current state of health and hypothetical progressive
      dementia were assessed on a Likert scale. The same interviewer contacted patient
      identified surrogate decision makers within 48 hours. Independently, a survey of
      community ophthalmologists was performed. The concordance of surrogate
      predictions with patient preferences (32 pairs) was assessed using percentage
      agreement, the kappa coefficient with dichotomous Likert scale data, and chi
      square analyses (concordance beyond chance). RESULTS: In their current state of
      health, most patients said they would prefer to have surgery if they were deemed
      to have a visually significant cataract, which was accurately predicted by
      surrogates (72% agreement, kappa = 0.65, chi square = 16.5). In a hypothetical
      dementia scenario, contrary to perceptions of patients and their surrogates,
      proxies were unable to accurately represent a patient's wishes for elective
      cataract surgery (34% agreement, kappa = 0.23, chi square = 14.4). Physicians
      tended to withhold intervention in the dementia scenario. CONCLUSIONS: The
      findings suggest that current methods of decision making in elective surgery for
      patients unable to make autonomous decisions may be seriously flawed. This
      extends previous findings of inaccuracy with the substituted judgment approach to
      end-of-life issues to reflect elective surgical scenarios.

PMID- 18053911
TI  - Primary intravitreal bevacizumab for the management of pseudophakic cystoid
      macular edema: pilot study of the Pan-American Collaborative Retina Study Group.
AB  - PURPOSE: To determine the feasibility, safety, and clinical effect of primary
      intravitreal bevacizumab (Avastin) in patients with cystoid macular edema (CME)
      after cataract surgery. SETTING: Five institutions in Venezuela, Costa Rica,
      Puerto Rico, Peru, and Brazil. METHODS: Twenty-eight eyes of 25 patients treated
      with at least 1 intravitreal injection of 1.25 mg or 2.50 mg of Avastin
      participated in this interventional retrospective multicenter study at 5
      institutions from 5 countries. Baseline and follow-up visits included Early
      Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing, optical
      coherence tomography (OCT) imaging, and ophthalmoscopic examination. RESULTS: The
      mean follow-up was 32 weeks (range 24 to 52 weeks). Twenty eyes (71.4%) had
      improved best corrected visual acuity (BCVA) (> or =2 ETDRS lines), and no eye
      had worse visual acuity (> or =2 ETDRS lines). The BCVA remained stable in 8 eyes
      (28.6%). The mean baseline BCVA was 20/160 (logMAR = 0.92) and the mean final
      BCVA, 20/63 (logMAR = 0.50); the difference was statistically significant
      (P<.0001). The mean central macular thickness at baseline (466.3 microm; range
      208 to 784 microm) decreased significantly (264.5 microm; range 176 to 513
      microm) by the end of follow-up (P<.0001). Eight eyes (28.6%) required a second
      injection and 4 (14.3%), a third injection. The mean interval between injections
      was 13 weeks (range 5 to 26 weeks). No ocular or systemic adverse events were
      observed. CONCLUSIONS: Short-term results suggest that primary intravitreal
      Avastin is well tolerated in patients with pseudophakic CME. Treated eyes had a
      significant improvement in BCVA and decrease in macular thickness by OCT.

PMID- 18053912
TI  - Clinical features and outcomes of pars plana vitrectomy in patients with retained
      lens fragments after phacoemulsification.
AB  - PURPOSE: To review the clinical features and outcomes of pars plana vitrectomy
      (PPV) in patients with retained lens fragments after phacoemulsification and
      compare the results with those in previous studies. SETTING: Department of
      Ophthalmology, Queen's Medical Centre, Nottingham, United Kingdom. METHODS: This
      retrospective chart review comprised 82 consecutive eyes of 82 patients who had
      vitrectomy for retained lens material after phacoemulsification between January
      2000 and June 2006. Data on demographics, preexisting eye conditions, cataract
      surgery details, findings at presentation, interval between phacoemulsification
      and vitrectomy, details of vitrectomy, details of follow-up visits, and
      postoperative complications were collected. RESULTS: The incidence of raised
      intraocular pressure (IOP) was 46.3%. Anterior vitrectomy was associated with a
      lower incidence of increased IOP (P = .006). There was no association between
      late vitrectomy and a worse visual outcome. There was a much lower rate of
      complications than in other studies; the incidence of retinal detachment and of
      cystoid macular edema was 4.9%, and there were no cases of endophthalmitis.
      CONCLUSION: The incidence of raised IOP in patients who had anterior vitrectomy
      at the time of cataract surgery was low. The visual outcomes were good, and the
      incidence of complications was low irrespective of the timing of the PPV.

PMID- 18053913
TI  - Image quality with multifocal intraocular lenses and the effect of pupil size:
      comparison of refractive and hybrid refractive-diffractive designs.
AB  - PURPOSE: To analyze the image quality with a refractive and 2 hybrid refractive
      diffractive multifocal intraocular lenses (IOLs) in vitro to determine the IOL
      modulation transfer function (MTF) following the EN-ISO international standard
      for distance and near vision and to study the IOLs' behavior with different pupil
      sizes. SETTING: Fundacion Oftalmologica del Mediterraneo, Valencia, Spain.
      METHODS: This study evaluated 4 IOLs: the hybrid refractive-diffractive AcrySof
      ReSTOR SN60D3 (Alcon) and Tecnis ZM900 (AMO), the refractive ReZoom NXG (AMO),
      and the monofocal AcrySof SN60WF (Alcon). The MTF was calculated from the cross
      line spread function recorded with the OPAL Vector System (Image Science Ltd.)
      using fast Fourier transform techniques. The artificial eye model simulated in
      vivo conditions of the anterior chamber and included an artificial cornea and
      physiological solution, in which the IOLs were positioned. The pupil sizes varied
      between 2.0 mm and 5.0 mm in steps of 0.5 mm. RESULTS: For distance vision and
      small pupils (2.0 to 3.5 mm), the refractive IOL provided better image quality
      than the 2 hybrid IOLs. When the pupil was larger, the distance vision was
      similar with all IOLs. The 2 hybrid IOLs gave better image quality than the
      refractive IOL for near vision with any pupil size. With the refractive IOL and
      pupils smaller than 3.5 mm, near focusing did not occur, resulting in poor image
      quality. Of the hybrid IOLs, the AcrySof ReSTOR SN60D3 provided better distance
      image quality and the Tecnis ZM900 provided better near image quality.
      CONCLUSIONS: The refractive IOL gave better image quality than the hybrid IOLs at
      distance and with small pupils. With pupils larger than 3.5 mm, the quality was
      similar. Hybrid IOLs gave significantly better image quality for near vision with
      all pupil sizes. AcrySof ReSTOR SN60D3 IOLs give better distance vision than
      Tecnis ZM900 IOLs; the latter gave better near vision. The reference monofocal
      IOL provided better distance images than any multifocal IOL with all pupil sizes.

PMID- 18053914
TI  - Epi-LASIK using the Amadeus II microkeratome: evaluation of cut quality using
      light and electron microscopy.
AB  - PURPOSE: To investigate the cut quality and surface characteristics of the
      epithelial flap and underlying Bowman's membrane created by the Amadeus II (AMO)
      microkeratome on human corneas using light and electron microscopy. SETTING:
      Center for Refractive Therapy, Department of Ophthalmology, Ludwig-Maximilians
      University, Munich, Germany. METHODS: Using a 9.0 mm type II suction ring and
      settings, as recommended by the manufacturer, epithelial laser in situ
      keratomileusis (epi-LASIK) was performed in 2 fresh human eyes of 1 donor. Ocular
      pathology and previous ocular surgery were ruled out. Tissues for light
      microscopy were examined using hematoxylin-eosin and periodic acid-Schiff
      reaction staining. Further tissue samples were examined using scanning electron
      microscopy and transmission electron microscopy. RESULTS: Light microscopy showed
      a thoroughly separated epithelial sheet with no evident anatomical abnormalities.
      Stratification of the separated epithelium layer and cell shape was conserved.
      The cleavage plane was located at Bowman's membrane. Scanning electron microscopy
      showed a consistent transition from adherent epithelium to the denuded area.
      Bowman's layer showed a very smooth surface without remains of basal lamina.
      Transmission electron microscopy examination showed interruptions of the basement
      membrane at high magnification. CONCLUSIONS: This in vitro study found a high cut
      quality using the epi-LASIK separator of the Amadeus II microkeratome. The
      resulting cleavage plane at Bowman's membrane was well suited for the subsequent
      laser ablation.

PMID- 18053915
TI  - Safety and efficacy of intracapsular tranilast microspheres in experimental
      posterior capsule opacification.
AB  - PURPOSE: To evaluate the safety and efficacy of a sustained-release agent
      designed to reduce posterior capsule opacification (PCO). SETTING: Department of
      Ophthalmology, EENT Hospital, Fudan University, Shanghai, Peoples Republic of
      China. METHODS: Free tranilast (TFree) was incorporated into polylactic acid
      microspheres and then tested using a rabbit model of PCO. Twenty-nine rabbits
      were randomized into 5 groups treated with balanced saline solution (BSS
      control); TFree; or 0.5, 1.0, or 2.0 mg tranilast microspheres (TMicro). Standard
      phacoemulsification cataract surgery, including manual aspiration of all visible
      soft lens matter, was performed in all groups. The selected test agent was then
      injected into the lens capsule. Postoperative clinical examinations were
      performed at 1, 3, 7, 14, 30, 60, and 90 days. Posterior capsule opacification
      was quantified using high-resolution computer image analysis at 1, 2, and 3
      months. Histological examination was performed at 3 months. RESULTS: Eyes treated
      with TMicro had significantly less PCO than the eyes in the BSS and TFree groups.
      While the BSS control eyes had increased PCO over 3 months, eyes in the TMicro
      group had reduced PCO over time in a dose-dependent fashion. Histological
      examination showed reduced lens epithelial cell proliferation in the TMicro
      groups, with no manifest damage to the cornea, iris, or retina compared with the
      BSS controls. There was a transient increase in postoperative inflammation in all
      tranilast-treated groups compared with the BSS controls. CONCLUSION: Sustained
      release intracapsular tranilast reduced PCO in an experimental model of PCO,
      suggesting further investigation of its therapeutic potential is justified.

PMID- 18053916
TI  - Ingress of bacterial inoculum into the anterior chamber after bimanual and
      microcoaxial phacoemulsification in rabbits.
AB  - PURPOSE: To compare the amount of bacterial ingress from the ocular surface into
      the anterior chamber at the end of bimanual and microcoaxial phacoemulsification
      in rabbits. SETTING: Iladevi Cataract & IOL Research Centre, Raghudeep Eye
      Clinic, Memnagar, Ahmedabad, India. METHODS: This randomized study comprised 40
      eyes of 20 rabbits. Rabbits had microcoaxial phacoemulsification through a 2.2 mm
      single-plane clear corneal incision or bimanual phacoemulsification through a
      clear corneal 1.2 mm incision for phaco tip access accompanied by an additional
      1.4 mm incision for irrigating chopper access. At the end of lens removal, 0.5 mL
      of culture suspension of Staphylococcus epidermidis (105 colony-forming units
      [CFU]/mL) was instilled on the ocular surface and kept for 2 minutes. Next, 0.1
      mL of aqueous fluid was collected from the anterior chamber and subjected to a
      microbial viable count. RESULTS: The microcoaxial group had statistically
      significantly lower ingress of bacteria than the bimanual group (250.0 CFU/mL and
      1538.1 CFU/mL, respectively) (P<.002) irrespective of the presence or absence of
      wound distortion. CONCLUSION: Bacterial ingress occurred in both groups, although
      it was statistically significantly higher in the bimanual group.

PMID- 18053917
TI  - Diffuse lamellar keratitis after corneal crosslinking in a patient with post
      laser in situ keratomileusis corneal ectasia.
AB  - A 27-year-old man presented with corneal ectasia in his left eye 4 years after
      myopic laser in situ keratomileusis (LASIK) and was treated with riboflavin
      ultraviolet-A (crosslinking). During the first post-treatment days, diffuse
      lamellar keratitis (DLK) (stage III) developed. The microbiology culture was
      negative. After intensive treatment with topical corticosteroids, the DLK
      resolved during the following 2 weeks. Crosslinking for post-LASIK corneal
      ectasia may induce DLK. Early diagnosis and appropriate treatment with intensive
      topical corticosteroids is essential to successfully manage this post
      crosslinking complication.

PMID- 18053918
TI  - Intacs to stabilize diurnal variation in refraction after radial keratotomy.
AB  - We present a patient who was dissatisfied with the refractive results of the
      radial keratotomy procedure he had 8 years previously, specifically the
      instability of the visual acuity and refractive error throughout the day. To
      reverse the biomechanical disturbance caused by the incisions, an intracorneal
      ring segment (Intacs, Addition Technology, Inc.) was inserted in the inferior
      cornea. The variation in refraction decreased from 1.50 and 2.25 diopters (D) to
      0.25 and 0.50 D, resulting in a very satisfied patient.

PMID- 18053919
TI  - Intraoperative floppy-iris syndrome and finasteride intake.
AB  - We report 2 male patients who had bilateral cataract surgery. Both patients had
      features of the intraoperative floppy-iris syndrome (IFIS) in both eyes, and both
      were taking oral finasteride for the management of benign prostatic hyperplasia
      (BPH). We conclude that finasteride can be associated with IFIS, so it is
      important to take detailed medical histories of patients having cataract surgery,
      paying attention to a history of BPH and its treatment.

PMID- 18053920
TI  - Possible protection of the posterior segment by a phakic intraocular lens.
AB  - A 39-year-old man was referred with complaints of pain, redness, and reduced
      vision in the left eye after projectile trauma during hammering. Two years
      previously, anterior chamber phakic intraocular lenses (pIOLs) had been implanted
      to correct the patient's high myopia. On presentation, the best corrected visual
      acuity was 20/30 in the right eye and 20/50 in the left eye. Slitlamp examination
      disclosed a central self-sealed corneal laceration in the left eye, and
      gonioscopy and a high-resolution computed tomography scan showed a metallic
      intraocular foreign body (IOFB) lodged in the anterior chamber angle. After the
      foreign body was removed, the patient regained his previous visual acuity. In
      this case, the pIOL may have prevented further penetration of the IOFB and
      protected the crystalline lens and posterior segment.

PMID- 18053921
TI  - Cataract surgery and anterior megalophthalmos: custom intraocular lens and
      special considerations.
AB  - We report a patient who presented with anterior megalophthalmos: corneal diameter
      of nearly 17.0 mm, anterior chamber depth of 7.0 mm, mild lens subluxation, and
      nuclear sclerotic cataract. Surgical management consisted of a scleral tunnel
      incision, capsule staining, a predetermined capsulorhexis size, microcoaxial
      phacoemulsification with torsional ultrasound, and implantation of a custom IOL
      to ensure endocapsular fixation. Special consideration must be given to the
      patient with a very large anterior segment.

PMID- 18053922
TI  - Traumatic fracture of posterior chamber intraocular lens.
AB  - An 18-year-old man developed a fracture in a single-piece polymethylmethacrylate
      posterior chamber (PC) intraocular lens (IOL) at the optic-haptic junction with
      dislocation of the IOL into the anterior chamber after a fist injury to the eye.
      The dislocated IOL was explanted and replaced with another PC IOL.

PMID- 18053923
TI  - Bilateral asymmetrical isolated lens coloboma with persistent pupillary membrane.

PMID- 18053924
TI  - Tisseel and Tutoplast cover.

PMID- 18053925
TI  - Bromphenol blue staining in eyes with mature cataract.

PMID- 18053926
TI  - Combo-chop nuclear disassembly.

PMID- 18053927
TI  - Science, medicine and nationalism in the Habsburg Empire from the 1840s to 1918.

PMID- 18053928
TI  - 'A civilizing mission'? Austrian medicine and the reform of medical structures in
      the Ottoman Empire, 1838-1850.
AB  - During the 1840s, physicians from the Habsburg Empire played a decisive role in
      the reform of medical structures in the Ottoman Empire. This paper discusses
      different aspects of this scientific and cultural encounter. It emphasizes the
      importance of Austrian health care structures as a model for the work of these
      physicians in the Ottoman Empire and studies the role of the medical school ran
      by the Austrians as a means of representing, on the one hand, the reformatory
      efforts of the Ottoman Empire and, on the other hand, the motivations of the
      Habsburg monarchy for an involvement in Ottoman health care affairs, strongly
      bound up with its own quarantine politics towards the Ottoman Empire.

PMID- 18053929
TI  - The Magyar moustache: the faces of Hungarian state formation, 1867-1918.
AB  - This paper outlines the history of Hungarian ethnography and anthropology and
      their role in the construction of the nation and Hungarian liberalism in the
      Dualist period (1867-1918). Affected by the specific socio-political conditions
      of this ethnically most diverse country of contemporary Europe, the disciplinary
      trajectories of Hungarian ethnography and anthropology diverge considerably from
      the models offered by the historiography in the British, French and German
      contexts. The paper argues that the pluralistic, cultural and strongly
      integrative ethnographic tradition that prevailed in Hungary in the last decades
      of the nineteenth century did not notably wane and shift towards a biological,
      hierarchical and racialist thinking by the end of the First World War.
      Furthermore, Hungarian liberalism did not simply provide the milieu for these
      disciplines to flourish, but was itself partly the result of these disciplines'
      attempts to formulate the very concepts of ethnicity and race.

PMID- 18053930
TI  - Psychiatric institutions, their architecture, and the politics of regional
      autonomy in the Austro-Hungarian monarchy.
AB  - This paper examines the planning process and architecture of two public
      psychiatric institutions built around 1900 in Trieste and Lower Austria. From
      1864, the building of new asylums was the responsibility of Crown land
      governments, which by the end of the nineteenth century had emerged as sites of
      power and self-presentation by minority groups and new political parties. At the
      same time, the area of asylum planning was establishing itself as a branch of
      asylum psychiatry and promoting the idea of the asylum as model settlement,
      contributing to social reform. I analyse the interaction of psychiatrists,
      architects and government officials involved in planning the two institutions in
      the context of Crown land governments' self-positioning within the empire and
      internationally (especially in relation to Italy and Germany). The Trieste asylum
      planners were working for a government controlled by Italian nationalists, but
      their desire for a 'modern' asylum turned them towards German models. The
      Christian Social government in Lower Austria sought to supplant Germany as the
      leader in this branch of science. The spatial arrangement and visual articulation
      of the two asylums is interpreted in the context of the interaction of psychiatry
      and the politics of regional autonomy.

PMID- 18053931
TI  - Surgery and national identity in late nineteenth-century Vienna.
AB  - For historians of medicine, the professor Theodor Billroth of the University of
      Vienna was the leading European surgeon of the late nineteenth century and the
      personification of intervention by organ or body part removal. For social and
      political historians, he was a German nationalist whose book on medical education
      heralded the rise of anti-Semitism in the Austrian public sphere. This article
      brings together and critically reassesses these two hitherto separate accounts to
      show how, in a period of dramatic social and political change, Viennese surgery
      split into two camps. One, headed by Billroth, was characterized by an alliance
      with the German educational model, German nationalism leading to racial anti
      Semitism and an experimental approach to the construction of surgical procedure,
      which heavily relied on the methods of pathological physiology. The other, which
      followed a long Austrian tradition, stood for a clinically oriented and strictly
      organized medical education that catered to an ethnically and socially diverse
      population and, simultaneously, for an anatomically oriented surgery, largely of
      the locomotor apparatus. This study shows how, in a major centre of medical
      education and capital of a multiethnic empire, surgical and national identities
      were forged together.

PMID- 18053932
TI  - Towards a philosophy of microbiology.

PMID- 18053933
TI  - The structure of microbial evolutionary theory.
AB  - The study of microbial phylogeny and evolution has emerged as an
      interdisciplinary synthesis, divergent in both methods and concepts from the
      classical evolutionary biology. The deployment of macromolecular sequencing in
      microbial classification has provided a deep evolutionary taxonomy hitherto
      deemed impossible. Microbial phylogenetics has greatly transformed the landscape
      of evolutionary biology, not only in revitalizing the field in the pursuit of
      life's history over billions of years, but also in transcending the structure of
      thought that has shaped evolutionary theory since the time of Darwin. A trio of
      primary phylogenetic lineages, along with the recognition of symbiosis and
      lateral gene transfer as fundamental processes of evolutionary innovation, are
      core principles of microbial evolutionary biology today. Their scope and
      significance remain contentious among evolutionists.

PMID- 18053934
TI  - Hybrids, pure cultures, and pure lines: from nineteenth-century biology to
      twentieth-century genetics.
AB  - Prompted by recent recognitions of the omnipresence of horizontal gene transfer
      among microbial species and the associated emphasis on exchange, rather than
      isolation, as the driving force of evolution, this essay will reflect on
      hybridization as one of the central concerns of nineteenth-century biology. I
      will argue that an emphasis on horizontal exchange was already endorsed by
      'biology' when it came into being around 1800 and was brought to full fruition
      with the emergence of genetics in 1900. The true revolution in nineteenth-century
      life sciences, I maintain, consisted in a fundamental shift in ontology, which
      eroded the boundaries between individual and species, and allowed biologists to
      move up and down the scale of organic complexity. Life became a property
      extending both 'downwards', to the parts that organisms were composed of, as well
      as 'upwards', to the collective entities constituted by the relations of exchange
      and interaction that organisms engage in to reproduce. This mode of thinking was
      crystallized by Gregor Mendel and consolidated in the late nineteenth-century
      conjunction of biochemistry, microbiology and breeding in agro-industrial
      settings. This conjunction and its implications are especially exemplified by
      Wilhelm Johannsen's and Martinus Beijerinck's work on pure lines and cultures. An
      understanding of the subsequent constraints imposed by the evolutionary synthesis
      of the twentieth century on models of genetic systems may require us to rethink
      the history of biology and displace Darwin's theory of natural selection from
      that history's centre.

PMID- 18053935
TI  - Bacteria are small but not stupid: cognition, natural genetic engineering and
      socio-bacteriology.
AB  - Forty years' experience as a bacterial geneticist has taught me that bacteria
      possess many cognitive, computational and evolutionary capabilities unimaginable
      in the first six decades of the twentieth century. Analysis of cellular processes
      such as metabolism, regulation of protein synthesis, and DNA repair established
      that bacteria continually monitor their external and internal environments and
      compute functional outputs based on information provided by their sensory
      apparatus. Studies of genetic recombination, lysogeny, antibiotic resistance and
      my own work on transposable elements revealed multiple widespread bacterial
      systems for mobilizing and engineering DNA molecules. Examination of colony
      development and organization led me to appreciate how extensive multicellular
      collaboration is among the majority of bacterial species. Contemporary research
      in many laboratories on cell-cell signaling, symbiosis and pathogenesis show that
      bacteria utilise sophisticated mechanisms for intercellular communication and
      even have the ability to commandeer the basic cell biology of 'higher' plants and
      animals to meet their own needs. This remarkable series of observations requires
      us to revise basic ideas about biological information processing and recognise
      that even the smallest cells are sentient beings.

PMID- 18053936
TI  - From quorum to cooperation: lessons from bacterial sociality for evolutionary
      theory.
AB  - The study of cooperation and altruism, almost since its inception, has been
      carried out without reference to the most numerous, diverse and very possibly
      most cooperative domain of life on the planet: bacteria. This is starting to
      change, for good reason. Far from being clonal loners, bacteria are highly social
      creatures capable of astonishingly complex collective behaviour that is mediated,
      as it is in colonial insects, by chemical communication. The article discusses
      recent experiments that explore different facets of current theories of the
      evolution and maintenance of cooperation using bacterial models. Not only do
      bacteria hold great promise as experimentally tractable, rapidly evolving systems
      for testing hypotheses, bacterial experiments have already raised interesting
      questions about the assumptions on which our current understanding of cooperation
      and altruism rests.

PMID- 18053937
TI  - Metagenomics and biological ontology.
AB  - Metagenomics is an emerging microbial systems science that is based on the large
      scale analysis of the DNA of microbial communities in their natural environments.
      Studies of metagenomes are revealing the vast scope of biodiversity in a wide
      range of environments, as well as new functional capacities of individual cells
      and communities, and the complex evolutionary relationships between them. Our
      examination of this science focuses on the ontological implications of these
      studies of metagenomes and metaorganisms, and what they mean for common sense and
      philosophical understandings of multicellularity, individuality and organism. We
      show how metagenomics requires us to think in different ways about what human
      beings are and what their relation to the microbial world is. Metagenomics could
      also transform the way in which evolutionary processes are understood, with the
      most basic relationship between cells from both similar and different organisms
      being far more cooperative and less antagonistic than is widely assumed. In
      addition to raising fundamental questions about biological ontology, metagenomics
      generates possibilities for powerful technologies addressed to issues of climate,
      health and conservation. We conclude with reflections about process-oriented
      versus entity-oriented analysis in light of current trends towards systems
      approaches.

PMID- 18053938
TI  - Epistemological issues in the study of microbial life: alternative terran
      biospheres?
AB  - The assumption that all life on Earth today shares the same basic molecular
      architecture and biochemistry is part of the paradigm of modern biology. This
      paper argues that there is little theoretical or empirical support for this
      widely held assumption. Scientists know that life could have been at least
      modestly different at the molecular level and it is clear that alternative
      molecular building blocks for life were available on the early Earth. If the
      emergence of life is, like other natural phenomena, highly probable given the
      right chemical and physical conditions then it seems likely that the early Earth
      hosted multiple origins of life, some of which produced chemical variations on
      life as we know it. While these points are often conceded, it is nevertheless
      maintained that any primitive alternatives to familiar life would have been
      eliminated long ago, either amalgamated into a single form of life through
      lateral gene transfer (LGT) or alternatively out-competed by our putatively more
      evolutionarily robust form of life. Besides, the argument continues, if such life
      forms still existed, we surely would have encountered telling signs of them by
      now. These arguments do not hold up well under close scrutiny. They reflect a
      host of assumptions that are grounded in our experience with large multicellular
      organisms and, most importantly, do not apply to microbial forms of life, which
      cannot be easily studied without the aid of sophisticated technologies.
      Significantly, the most powerful molecular biology techniques available
      polymerase chain reaction (PCR) amplification of rRNA genes augmented by
      metagenomic analysis-could not detect such microbes if they existed. Given the
      profound philosophical and scientific importance that such a discovery would
      represent, a dedicated search for 'shadow microbes' (heretofore unrecognized
      'alien' forms of terran microbial life) seems in order. The best place to start
      such a search is with puzzling (anomalous) phenomena, such as desert varnish,
      that resist classification as 'biological' or 'nonbiological'.

PMID- 18053940
TI  - Infant feeding: initiation, problems, approaches.

PMID- 18053943
TI  - First human experience with local delivery of novel antisense AVI-4126 with
      Infiltrator catheter in de novo native and restenotic coronary arteries: 6-month
      clinical and angiographic follow-up from AVAIL study.
AB  - BACKGROUND: A novel antisense phosphorodiamidate morpholino oligomer, AVI-4126,
      was shown to be effective in reducing neointimal formation in different animal
      models following delivery by pluronic gels, porous balloon catheters, and coated
      stents. The purpose of the AVAIL study was to investigate both the safety and the
      efficacy of AVI-4126 delivered locally via Infiltrator catheter after
      percutaneous coronary intervention in humans. METHODS: The AVAIL trial is a
      prospective, evaluator-blinded, randomized study including clinical follow-up at
      30 days and 6 months after intervention and 6-month angiographic and
      intravascular ultrasound (IVUS) follow-up. An Infiltrator catheter was advanced
      to target lesion and either drug was delivered (Groups A and B) or catheter was
      advanced (Group C) after stent implantation in de novo lesions or percutaneous
      transluminal coronary angioplasty in restenotic lesions. Primary end points
      include major adverse cardiovascular events (MACE), target vessel
      revascularization (TVR), angiographic restenosis, and IVUS at 6 months. RESULTS:
      Forty-four patients with either de novo lesions or restenosis were randomized
      into three groups: (A) low dose, 3 mg (19 patients); (B) high dose, 10 mg (15
      patients), and (C) control (10 patients). Baseline angiographic characteristics
      did not differ between the groups (reference vessel diameter, 2.5-4 mm; lesion
      length, <16 mm). Procedural success was 81. 82% (unable to advance Infiltrator
      catheter to target lesion in 8 patients, 5 from Group B and 3 from Group C).
      There was no in-hospital or 30-day MACE recorded in any group. Clinical follow-up
      was available in 25 patients. At 6 months, four patients (50%) from the control
      group (Group C, n=8) and 7 (100%) patients from the low-dose group (Group A, n=7)
      required TVR. In contrast, in the high-dose group (Group B, n=10) only 1 patient
      (10%) needed TVR. Angiographic follow-up in 25 patients (Group A, 8 patients;
      Group B, 7 patients; and Group C, 10 patients) demonstrated late loss of 1.4+ to
      0.54, 0.8+ to 0.55, and 1.5+ to 0.65, respectively (P=.025). Binary restenosis
      was 38% in Group C (control), 29% in Group A (low dose), and 0% in Group B (high
      dose). CONCLUSION: Local delivery of antisense is feasible. These preliminary
      findings from the small cohort of patients require confirmation in a larger trial
      utilizing more sophisticated drug-eluting technologies.

PMID- 18053944
TI  - Angiographic and clinical characteristics associated with the removable plaque
      components by means of thrombectomy catheters in patients with myocardial
      infarction.
AB  - BACKGROUND: Previous studies have demonstrated that atheroembolism during
      percutaneous coronary intervention is associated with myocardial damage. The
      purpose of this study is to investigate the clinical and angiographic
      characteristics related to removable plaque elements in patients undergoing
      thrombectomy for myocardial infarction. METHODS: Eighty consecutive lesions in 80
      patients (M/F=58/22, age 65.5+/-11.6 years) with myocardial infarction who
      underwent thrombectomy (TVAC system, Nipro, Osaka, Japan) prior to mechanical
      dilatation (balloon angioplasty and/or stent implantation) were investigated.
      Visible debris was collected and plaque elements (cholesterol clefts and/or foamy
      cells) were investigated pathologically. Baseline angiographic characteristics
      [baseline thrombolysis in myocardial infarction (TIMI) grade, culprit lesion,
      haziness, lesion length, ostium, bifurcation, calcification, eccentricity,
      thrombus, and multivessel] were analyzed, and predictive angiographic and
      clinical factors for plaque elements were investigated. RESULTS: There were no
      complications related to thrombectomy. Final TIMI grade 3 and blush grade 2 or 3
      were achieved in 75 (94%) and 66 (83%) patients, respectively. Visible debris
      specimens were obtained in 49 (61%) patients. Histological plaque elements
      (cholesterol clefts and/or foamy cells) were observed in 27 out of 49 patients
      with debris specimens. There was no significant difference in the clinical
      characteristics between the groups of patients with (group P) and without (group
      NP) plaque elements. Aspirated plaque elements were more frequently observed in
      discrete and eccentric lesions (group P vs. group NP: discreteness, 52% vs. 28%,
      P<.05; eccentricity, 67% vs. 36%, P<.05). CONCLUSIONS: This study demonstrated
      the clinical characteristics associated with removable plaque components in
      patients with myocardial infarction undergoing thrombectomy by means of the TVAC
      system. Discreteness and eccentricity were more frequently observed in lesions
      with removable plaque elements.

PMID- 18053945
TI  - Stent thrombosis following drug-eluting stent implantation. A single-center
      experience.
AB  - BACKGROUND: The risk of stent thrombosis (ST) following drug-eluting stent (DES)
      implantation may extend beyond the initial period after successful implantation.
      METHODS: We evaluated the incidence, timing, and clinical outcomes of patients
      who presented with DES-related early (<or=30 days) and late (>30 days)
      angiographic ST. Between 1/2004 and 9/2006, a total of 1339 patients underwent
      DES implantation (90% using Cypher stents) at our institution. Dual antiplatelet
      therapy was recommended for 3 to 12 months. Clinical follow-up was obtained and
      adjudicated at 1 and 6 months following any ST event. RESULTS: We identified
      eight patients (0.6% of the total patients treated with DES) with definite ST.
      Their mean age was 67+/-13 years. Six patients (75%) were male and 37.5% (3/8)
      had diabetes. Acute myocardial infarction (AMI) was the clinical presentation in
      87.5% of patients. Time to ST was 4 days in two (25%) of eight patients. The
      other six patients (75%) had late ST (>30 days). The median time to late ST was
      480 days (range: 90-1080 days). Two patients had recurrent events of late ST. All
      cases of late ST, except one, occurred after clopidogrel treatment was
      discontinued. Median time from clopidogrel withdrawal to late ST was 18 months
      (range: 0.5-35 months). At 6 months' follow-up from the time of ST, the
      subsequent major adverse cardiac event (MACE) rate (including death, re
      infarction, recurrent ST or need for emergent CABG) was 62.5% and overall and/or
      cardiac mortality rate was 12.5%. CONCLUSION: We found that ST occurred
      infrequently (0.6%) and the majority (75%) of patients developed ST late (>30
      days) and beyond the period recommended for dual anti-platelet pharmacotherapy.
      Major adverse cardiac events following ST are substantial at 6 months and thus
      deserve careful clinical attention.

PMID- 18053946
TI  - Incidence of extracerebral paradoxical embolisms in patients with intracardiac
      shunts.
AB  - BACKGROUND: Although extracerebral embolism accounts for 5-10% of all paradoxical
      embolisms, it still remains a ghostlike entity in cardiovascular pathophysiology.
      The aim of this brief report was to analyze the profile of patients with
      paradoxical extracerebral embolism and intracardiac shunts, and the role of shunt
      closure on the recurrence of extracerebral paradoxical embolism (EPE) in a
      population of patients evaluated for patent foramen ovale (PFO)/atrial septal
      defect (ASD) transcatheter closure. METHODS: From July 2003 to December 2006, 150
      patients (mean age 51.4+/-15.1 years, range13-78 years, M/F=49/101) were planned
      for transcatheter closure of PFO/ASD at our institutional program of Adult
      Congenital Heart Disease Management. Clinical history and medical records of all
      patients were reviewed searching for association of PFO/ASD, stroke, and
      presumptive EPE. RESULTS: Association of PFO with presumptive EPE was found in
      nine patients (6%, mean age 40.1+/-14 years, M/F=3/6). Five patients had ST
      elevation myocardial infarction (mean value of troponin was 15.3+/-2.1 ng/ml),
      while four patients had inferior limb acute ischemia. In patients with coronary
      embolism, coronary angiography was performed immediately after chest pain onset
      revealing normal coronary artery and only a mild hypokinesia. In patients with
      peripheral acute ischemia, early (>4 h from symptoms onset) angiography
      demonstrated normal main peripheral vessel and an embolic closure of popliteal
      artery (one patient), distal tibial artery (two patients), or peroneal artery
      (one patient) that normalized with heparin therapy in a few hours except in one
      patient. Migraine with aura was present in seven of nine patients. Cerebral MRI
      revealed previous ischemic areas in four of nine patients. Coagulation disorders
      were detected in six of nine patients. Echocardiography demonstrated a large to
      medium PFO in seven patients and a cribrosus ASD in two patients. CONCLUSION:
      Although a large study is required to assess optimal diagnosis and clinical
      implications of EPE, the clinical profile emerging from our study may help to
      identify some easy criteria of diagnosis in order to improve diagnosis and
      decrease the recurrence of such probably underestimated manifestations of
      PFO/ASD.

PMID- 18053947
TI  - Early vascular response to overlapped paclitaxel-eluting stents in swine coronary
      arteries.
AB  - BACKGROUND: The early response to the TAXUS Express2 paclitaxel-eluting stent
      (PES) system was compared to the response to the Express2 bare metal stent (BMS)
      system in porcine arteries. METHODS: Swine coronary arteries were implanted with
      overlapping PES or BMS and examined at 1, 2, 4, 10, and 20 days postimplantation
      using scanning electron microscopy or light microscopy. RESULTS: Vascular healing
      in terms of strut coverage, reendothelialization, degree of inflammation, and
      absence of thrombus was equivalent in both groups from 1 to 20 days. Interstrut
      member spaces were unaffected by stent deployment and remained covered with
      endothelium from Day 1. In both groups at 2 days, small patches of endothelial
      cells covered approximately 5-10% of the stent surface. At 4 days, endothelial
      cell coverage progressed to nearly 50% in both groups. After 10 days, endothelial
      cell strut coverage was nearly complete (>90%), with regions of incomplete
      coverage located primarily in strut overlap regions in both groups. BMS exhibited
      a fibrocellular neointima and no parastrut fibrin, whereas PES exhibited a
      developing but immature fibrocellular neointima and prominent parastrut fibrin.
      By Day 20, an endothelialized neointima was present in both groups, with
      comparable coverage of proximal and distal stented regions. The neointima of PES
      was more fibrocellular and parastrut fibrin was still comparable to that at 10
      days. CONCLUSION: Early vascular response was comparable for both PES and BMS,
      with similar rates of reendothelialization, limited inflammatory response, and
      absence of thrombus, but differed parastrut fibrin clearance and neointimal
      maturation rate.

PMID- 18053948
TI  - Efficacy and safety of pimecrolimus-eluting stents in porcine coronary arteries.
AB  - OBJECTIVE: We aimed to evaluate an effective dosage and safety profile of
      pimecrolimus as an anti-inflammatory drug for drug-eluting stents. METHODS: In
      the dose finding study, coronary arteries of 20 domestic swine were randomly
      implanted with bare metal stents (ProKinetic and Guidant Vision), the ProKinetic
      stent with polylactic acid (PLLA), and pimecrolimus-eluting stents (32, 75, and
      120 microg) over a period of 4 weeks. In addition, pimecrolimus (75 microg) and
      ProKinetic stents were randomly implanted into six swine over 3 months. In the
      safety study, the ProKinetic stent, the ProKinetic stent with PLLA, mid- (45
      microg) and high-dose pimecrolimus (120 microg), and overlapping mid-dose stents
      were implanted over a period of 4 weeks. Mid-dose, ProKinetic stent, and
      ProKinetic stent with PLLA were implanted over a period of 3 months. RESULTS: The
      dose finding study revealed excellent luminal patency with low percent occlusion
      (approximately 29% vs. approximately 41%), injury (0.53-0.59 vs. 1.25), and
      inflammation (0.78-0.97 vs. 1.08) for the pimecrolimus group compared with the
      vision group. The safety study arm showed similar angiographic results for all
      tested groups, with a significantly larger minimal lumen diameter for
      pimecrolimus stents compared to PLLA stents. Except for the high-dose group and
      overlapping area of the overlapping group, promising morphometric results were
      found for pimecrolimus compared to bare metal stents. CONCLUSIONS: Present data
      suggest that pimecrolimus-eluting stents are safe and have a similar healing
      profile to bare metal stents. They may suppress inflammation, leading to a
      reduced intimal response and a milder inflammatory reaction in a porcine model.

PMID- 18053949
TI  - Right ventricular involvement in a patient with isolated noncompaction of the
      ventricular myocardium.
AB  - Isolated noncompaction of the ventricular myocardium (INVM) is an unclassified
      cardiomyopathy and is thought to be due to arrest of myocardial morphogenesis.
      Although right ventricular involvement is not uncommon, the correct diagnosis is
      often difficult by echocardiography. In this report, we describe a patient with
      INVM in whom magnetic resonance imaging was useful to detect right ventricular
      morphological and functional abnormalities.

PMID- 18053950
TI  - Left main coronary artery aneurysm: report of three cases.
AB  - Left main coronary artery (LMCA) aneurysm is a rare coronary abnormality defined
      as localized coronary artery dilatations>1.5 to 2 times the diameter of the
      adjacent segments. The incidence of coronary artery aneurysm varies between 0.15%
      and 4.9%. It can be recognized by coronary angiography or multidetector computed
      tomography. Here, we present three cases of LMCA aneuryms, of one which firstly
      diagnosed by multidetected computed tomography.

PMID- 18053951
TI  - Glycoprotein IIb/IIIa inhibitors: questioning indications and treatment
      algorithms.
AB  - Glycoprotein inhibitors (GPI) are viewed as beneficial adjunctive pharmacotherapy
      agents for percutaneous coronary interventions (PCIs). The major benefit of GPI
      is derived from the reduction of ischemic events (mostly non-Q-wave myocardial
      infarctions) during PCI. There is no single randomized clinical trial
      demonstrating that any of these agents significantly reduces mortality in any
      clinical subset of patients. Studies of sustained oral GPI resulted in excessive
      death and myocardial infarctions. Reduction of ischemic end points was
      counteracted by excessive bleeding, vascular complications, and thrombocytopenia.
      These complications bear considerable medical and economic impact. The Acute
      Catheterization and Early Intervention Triage Strategy trial demonstrated that
      GPI, when added to heparin, enoxaparine, or bivalirudin, do not reduce mortality
      or ischemic events but significantly increase bleeding complications. Major
      bleeding resulted in threefold mortality at 1 year. In view of available data,
      the use of GPI should be limited to moderate-risk to high-risk PCI patients with
      low bleeding propensity. Protocols of abbreviated GPI administration and careful
      bleeding surveillance, in conjunction with lower doses of unfractionated heparin
      or new and possibly safer antithrombins, can potentially improve patient safety.

PMID- 18053952
TI  - Review: transient left ventricular apical ballooning, broken heart syndrome,
      ampulla cardiomyopathy, atypical apical ballooning, or Tako-Tsubo cardiomyopathy.
AB  - BACKGROUND: Transient left ventricular apical ballooning syndrome, also called
      "Tako-Tsubo cardiomyopathy," is increasingly being recognized as a cause of
      cardiomyopathy occurring during stress, with characteristic apical ballooning
      appearance of the left ventricle and the finding of normal coronary arteries on
      angiogram. In this manuscript, we review the available literature about the
      pathogenesis and characteristics of this syndrome.

PMID- 18053953
TI  - Optical coherence tomographic imaging of a bioabsorbable magnesium stent lost in
      a porcine coronary artery.

PMID- 18053954
TI  - Volunteer search and rescue and the American Red Cross: a Katrina response
      experience.
AB  - Major disasters like Hurricane Katrina cause severe damage. Often the bulk of the
      attention and aid is given to larger urban areas. Rural areas with its mix of
      poor and wealthy are often given far less attention or help is slower to arrive.
      These rural areas-where less is present before the disaster-often have nothing
      left after the event. This article chronicles the experience of a volunteer
      search and rescue organization working through the American Red Cross in its
      attempt to provide much-needed aid to one rural area in southwestern Mississippi.

PMID- 18053955
TI  - Nicaragua: an example of commitments and strengths despite problems of poverty.
AB  - Nicaragua is located in the middle of the Central American isthmus between the
      countries of Honduras and Costa Rica. It is the largest Central American country
      and is equivalent in size to the state of Georgia. Nicaragua is cited by Pan
      American Health Organization as one of the poorest third-world countries. One
      factor that continues to contribute to Nicaragua's chronic poverty state is the
      demographics of the country. Nearly half of all Nicaraguans are under 15 years of
      age, and more than a quarter are between the ages of 15 and 29 years. Only a
      quarter of the population is over 30 years of age. Beyond the hardship and
      poverty, there is a country rich in beauty. Nicaragua has a beautiful countryside
      with lush green mountains, black sand beaches of the Pacific Ocean, and the
      natural wonder of active volcanoes. It is easy to become engulfed by the
      tranquility of these surroundings and to steer away from the harsh conditions of
      the country. It is, however, a temporary escape from reality, for it was the
      hardships and unfavorable circumstances of this country that are never forgotten
      and which persist until today. This article focuses on a variety of interventions
      used to assist Nicaragua with their health care and state of well-being.

PMID- 18053956
TI  - Nursing recruitment: the importance of highlighting the diverse career paths for
      nurses.

PMID- 18053957
TI  - House and street: narratives of professional identity among nurses.
AB  - This study describes narratives of professional identity among nurses in Rio de
      Janeiro, Brazil. Semistructured interviews were carried out with 27 nursing
      professionals working in public hospitals in the city of Rio de Janeiro; in
      addition, the male:female ratio of graduate students of a nurse faculty in Rio de
      Janeiro was evaluated. Although the meaning of nursing is changing in Brazil, it
      is still strongly influenced by traditional values. We are observing in the last
      decades a shift in the meaning of nursing all over the world: from a female,
      domestic, and unvalued vocation to a more technical, masculine, and higher status
      profession. In Brazil, a coexistence of these two meanings, with a preponderance
      of the old traditional one, was observed. Change comes slowly. When the old model
      is challenged, it is often observed that the number of nurses per service
      decreases. The nurse often becomes the manager or leader of the unit. In these
      situations, patient care is displaced to less well trained individuals like
      technicians and nurse assistants who are not as well paid and, therefore, cost
      less to the system, while the responsibility of the results remains in the
      nurse's domain.

PMID- 18053958
TI  - One year later: reflections and work activities of accelerated second-degree
      bachelor of science in nursing graduates.
AB  - PURPOSE: This article shares the reflections and work activities of a cohort of
      graduates from an accelerated bachelor of science in nursing program. This survey
      was conducted following the 1-year anniversary of the students' graduation.
      SOURCE OF INFORMATION: Information for this study came from a mailed survey
      completed by program graduates. CONCLUSIONS: These graduates perceived that they
      had been effectively prepared through their program of study. Graduates'
      perception that they had a knowledge base for management of patient care is
      further evidence that accelerated programs can be successful in conveying an
      understanding of discipline-specific concepts and professional judgment. An
      important finding for the nursing workforce is that retention of these graduates
      is better than the norm. In addition, if the finding of the percentage of
      students planning to remain at the bedside is a consistent finding in future
      studies, this population of nurses may provide stability of the nurses practicing
      in the acute care setting.

PMID- 18053959
TI  - Web-based instruction: getting faculty onboard.
AB  - Although many colleges and universities have embraced distance education, a
      significant number still have not. Approximately 40% of faculty from these
      institutions have not accepted the value and legitimacy of online education
      [Allen, I. A., & Seaman, J. (2003). Sizing the opportunity: The quality and
      extent of online education in the United States, 2002, 2003. Needham, Mass: The
      Sloan Consortium]. One reason for this may be that faculty are not sufficiently
      informed about online learning and the role they might play in teaching in this
      environment. A number of salient issues are addressed: who our students are; what
      drives colleges and universities to offer distance education; which educational
      theory underpins distance education; how distance education fares in terms of
      quality as compared with face-to-face instruction; what the advantages and
      disadvantages of teaching online are; how teaching style is affected; and what
      types of support faculty need in providing instruction in this medium. Some
      recommendations are included for faculty who are considering teaching online. In
      this article, distance education refers to an asynchronous, web-based, and online
      format.

PMID- 18053960
TI  - Creating effective advisory boards for schools of nursing.
AB  - Increasingly, a significant priority for the dean and faculty in schools of
      nursing is fundraising. Raising financial resources is highly competitive and
      requires sophisticated approaches to building relationships with individual
      donors, government agencies, private foundations, and corporations. Fundraising
      efforts need to be designed to cultivate alumni, parents, and friends as key
      leaders educated in the work of the school, its vision for the future, and the
      nursing profession. Advisory boards, with an emphasis on development, can
      effectively nurture such leaders who are fully versed in the strategic vision of
      the school and who are willing to provide financial support and access to a broad
      community of interest. An integrated approach that capitalizes on the expertise
      and knowledge of the dean, the faculty, advancement officers, and a carefully
      selected board chair forms the foundation of a successful model for development
      focused advisory boards. Advisory board implementation is discussed from the
      perspective of a clearly articulated board charge, selection and recruitment,
      board retreat, assessment of interest and inclination through an annual board
      planning process, engagement in priority project planning with the faculty, and
      careful cultivation toward deepened relationships and funding.

PMID- 18053961
TI  - Recognizing and avoiding intercultural miscommunication in distance education a
      study of the experiences of Canadian faculty and aboriginal nursing students.
AB  - Language differences and diverse cultural norms influence the transmission and
      receipt of information. The online environment provides yet another potential
      source of miscommunication. Although distance learning has the potential to reach
      students in cultural groups that have been disenfranchised from traditional
      higher education settings in the past, intercultural miscommunication is also
      much more likely to occur through it. There is limited research examining
      intercultural miscommunication within distance education environments. This
      article presents the results of a qualitative study that explored the
      communication experiences of Canadian faculty and Aboriginal students while
      participating in an online baccalaureate nursing degree program that used various
      delivery modalities. The microlevel data analysis revealed participants' beliefs
      and interactions that fostered intercultural miscommunication as well as their
      recommendations for ensuring respectful and ethically supportive discourses in
      online courses. The unique and collective influences of intercultural
      miscommunication on the experiences of faculty and students within the courses
      are also identified. Instances of ethnocentrism and othering are illustrated,
      noting the effects that occurred from holding dualistic perspectives of us and
      them. Lastly, strategies for preventing intercultural miscommunication in online
      courses are described.

PMID- 18053962
TI  - Building bridges in academic nursing and health care practice settings.
AB  - The purpose of this article is to describe the development and implementation of
      a shared position with a focus on evidence-based practice (EBP) between the
      Visiting Nurse Service of New York and the Lienhard School of Nursing, Pace
      University. A preexisting relationship between the two institutions in providing
      student experiences in a community setting paved the way for the evolution a new
      collaborative effort. The shared position was initially conceived by two of the
      authors as an outcome of research they were conducting in the home care setting,
      which tested a model of mentoring frontline nurses in the EBP process on health
      care professional and patient outcomes. An initial conception of the new role
      provided a working document for discussions between the two institutions and the
      creation of a workable contract. The implementation of several initiatives has
      already provided support for the position, and each partner has benefited from
      building this bridge between nursing education and service. Benefits include
      advancing knowledge of and implementing EBP in both settings and promoting
      collaborative, clinically related scholarship.

PMID- 18053963
TI  - Clinical competence among senior nursing students after their preceptorship
      experiences.
AB  - The senior nursing preceptorship is the culminating clinical experience in the
      baccalaureate nursing program and assists students in the application of their
      nursing knowledge and skills. Students' success in getting their first job may
      also depend on this clinical preceptorship. How well they learn to practice their
      nursing skills before graduating may determine the success of their transition
      from being a student nurse to becoming a staff nurse. This descriptive study
      explored the perceptions of senior baccalaureate nursing students about their
      clinical preceptorship program. Perceptions were examined in relation to (a) the
      degree of students' interaction with the preceptor and (b) the degree of their
      perceptions of competence in using the nursing process. Data were collected from
      102 senior nursing students with the use of a 52-item survey questionnaire that
      included opinion and competence statements. The results suggest that the clinical
      preceptorship program increased the overall perceived competence of 91 of the 102
      nursing students. With a greater amount of preceptor interaction, there was a
      greater degree of perceived competence in nursing skills among the students.
      Ninety-six percent of the students rated their relationship with their preceptor
      as important to very important. The results also identified strong and weak areas
      of perceived clinical skills in the students. These results will help in
      facilitating future senior nursing preceptorship placements.

PMID- 18053964
TI  - Wash resistance of PermaNets in comparison to hand-treated nets.
AB  - The wash resistance of factory produced PermaNets (with deltamethrin bonded to
      the netting with a resin) was studied by bioassays with Anopheles stephensi.
      Commercial detergent powders were used to wash the nets. For comparison,
      conventionally treated nets were washed and bio-assayed. Nets were washed under
      laboratory conditions using a Rotary shaker for 10min. Mosquito bioassays used
      standard WHO plastic cones with an exposure time of 3min. The PermaNet caused
      almost a 100% mortality of An. stephensi after up to 18 washes and >80% mortality
      up to 26 washes but after 30 washes mortality declined. The differences between
      the mortality of An. stephensi on treated nets washed with detergent or soap
      (uncoloured, non-perfumed) were not significant. When conventional nets dipped in
      deltamethrin (25mg/m(2)) or lambdacyhalothrin (10mg/m(2)) were washed under
      similar laboratory conditions, the wash resistance was markedly less than that of
      the PermaNet. In the case of deltamethrin, mosquito mortality remained >80% up to
      12 washes and with lambdacyhalothrin mortality remained above 80% up to 11
      washes. The relationship of 80% mortality from a 3min bioassay to effectiveness
      against free flying mosquitoes remains to be determined.

PMID- 18053965
TI  - Effects of memantine on mitochondrial function.
AB  - Because NMDA complex and mitochondrial function are related, we hypothesized
      memantine would influence mitochondrial function. We addressed this in vitro by
      studying the effects of chronic and acute memantine exposures on mitochondrial
      function. For acute exposure experiments, mitochondria were isolated from NT2
      cells and assayed for electron transport chain (ETC) enzyme function and peroxide
      production in buffers containing up to 60uM memantine. For chronic exposure
      experiments, NT2 cells were maintained for at least two weeks in medium
      containing up to 60uM memantine, following which we assayed cells or their
      mitochondria for ETC enzyme activities, cytochrome oxidase protein levels,
      oxidative stress, calcium levels, and mitochondrial DNA levels. The ability of
      the NMDA receptor antagonist aminophosphonovaleric acid (APV) to modify
      memantine's mitochondrial effects was evaluated. Acute and chronic memantine
      similarly affected complex I (increased at high concentrations) and IV (decreased
      at high concentrations) V(max) activities. APV did not alter the effects of
      chronic memantine exposure on citrate synthase and complex IV. We detected a
      lower mitochondrial peroxide production rate with acute exposure, and an
      increased mitochondrial peroxide production rate with chronic exposure.
      Micromolar memantine concentrations affect mitochondria, some of these effects
      are directly mediated, and acute and chronic effects may differ.

PMID- 18053966
TI  - Rats selectively-bred for behavior related to affective disorders: proclivity for
      intake of alcohol and drugs of abuse, and measures of brain monoamines.
AB  - Several lines of rats potentially useful for studying affective disorders have
      been developed in our laboratory though selective breeding for behavioral
      characteristics. The propensity of these lines to consume alcohol and other drugs
      of abuse (amphetamine and cocaine) was examined. Also, measurement of the
      concentration of brain monoamines - norepinephrine, dopamine, and serotonin - as
      well as estimation of their metabolism by measurement of the major extracellular
      metabolites of these monoamines was carried out to examine possible relationships
      of brain chemistry to the behavioral characteristics shown by these lines, as
      well as to their propensity for drug usage. The lines of rats are: Swim Low
      active (SwLo) and Swim High-active (SwHi), which show either very low (SwLo) or
      very high (SwHi) amounts of motor activity in a swim test; Swim-test Susceptible
      (Susceptible or SUS) and Swim-test Resistant (Resistant or RES), which are highly
      susceptible (SUS) or highly resistant (RES) to having their swim-test activity
      depressed by being exposed to a stressful condition prior to the swim test; and
      Hyperactive (HYPER), which show spontaneous nocturnal hyperactivity compared to
      non-selectively bred (i.e., normal) rats as well as both extreme hyperactivity
      and behavioral depression after being exposed to a stressful condition. Regarding
      alcohol and drug usage, SUS rats readily consume alcohol while all other lines
      including non-selected, normal rats do not, and SwLo rats show a strong tendency
      to consume amphetamine and cocaine. Marked differences in brain monoamines were
      found between the various lines and normal rats, with salient differences seen in
      norepinephrine, particularly in the hippocampus, and in dopamine in forebrain
      regions (striatum and nucleus accumbens).

PMID- 18053967
TI  - Compensatory effects of the human nucleoside transporters on the response to
      nucleoside-derived drugs in breast cancer MCF7 cells.
AB  - Nucleoside transporters (NTs) are involved in the cytotoxicity and transcriptomic
      response induced by nucleoside analogues. A relationship between the expression
      of nucleoside transporters and response to therapy has been demonstrated in solid
      tumours, although the pattern of such expression is highly variable. Thus, a
      question is whether the transporter expression pattern rather than specific NT
      proteins might better explain the ability of tumour cells to respond to
      nucleoside-derived drug therapy. In this study we used the breast cancer cell
      lines MCF7 and MCF7-hCNT1 (stably transfected with hCNT1) to determine whether
      hCNT1 expression can complement hENT1 functional loss in the cytotoxicity and
      transcriptomic response triggered by nucleoside analogues. Expression of hCNT1
      slightly increased cell sensitivity to 5'-deoxy-5-fluorouridine (5'-DFUR).
      Inhibition of the endogenous equilibrative activity blocked 5'-DFUR cytotoxicity
      in MCF7 cells, but not in MCF7-hCNT1 cells. Moreover, under equilibrative
      transport inhibition conditions, induction of some transcriptional targets of 5'
      DFUR was blocked in MCF7 cells, whereas ENT-inhibition had no effect on the
      transcriptional response to 5'-DFUR in MCF7-hCNT1 cells. To confirm the role of
      hCNT1 in 5'-DFUR treatment, a panel of nucleoside derivatives suitable for hCNT1
      inhibition was obtained. The molecule T-Ala inhibited hCNT1-mediated transport.
      Furthermore, the cytotoxic action of 5'-DFUR and the transcriptional changes
      produced by this nucleoside analogue were partially inhibited by T-Ala in MCF7
      hCNT1 cells. These results show a link between NT function and the
      pharmacogenomic response to nucleoside analogues and further support the
      hypothesis that the expression pattern rather than specific transporters
      determines the cytotoxic effect of nucleoside derivatives.

PMID- 18053968
TI  - Induction of brain aquaporin 9 (AQP9) in catecholaminergic neurons in diabetic
      rats.
AB  - Aquaporin 9 facilitates the diffusion of water but also glycerol and
      monocarboxylates, known as brain energy substrates. AQP9 was recently observed in
      catecholaminergic neurons that are implicated in energy homeostasis and also
      possibly in neuroendocrine effects of diabetes. Recently it has been observed
      that the level of AQP9 expression in hepatocytes is sensitive to the blood
      concentration of insulin. Furthermore, insulin injection in the brain is known to
      be related to the energy homeostasis. Based on these observations, we
      investigated if the concentration of insulin affects the level of brain AQP9
      expression and if so, in which cell types. This study has been carried out, in a
      model of the diabetic rat generated by streptozotocin injection and on brainstem
      slices. In diabetic rats showing a decrease in systemic insulin concentration,
      AQP9 is only increased in brain areas containing catecholaminergic neurons. In
      contrast, no significant change is detected in the cerebral cortex and the
      cerebellum. Using immunocytochemistry, we are able to show that the increase in
      AQP9 expression is specifically present in catecholaminergic neurons. In
      brainstem slice cultures, 2 microM insulin induces a significant decrease in AQP9
      protein levels 6 h after application, suggesting that brain AQP9 is also
      regulated by the insulin. These results show that the level of expression of
      brain AQP9 is affected by variations of the concentration of insulin in a
      diabetic model and in vitro.

PMID- 18053969
TI  - Gamma oscillations in gerbil auditory cortex during a target-discrimination task
      reflect matches with short-term memory.
AB  - Tightly stimulus-locked "evoked" and not tightly stimulus-locked "induced" gamma
      band oscillations have been implicated in a variety of cognitive functions as
      well as more basic stimulus-related aspects of neuronal activity. The present
      study aimed at dissociating both aspects using a preparation in rodents trained
      to perform in a target-discrimination task while recording the intracerebral
      electrocorticogram in parallel from left and right auditory cortex. While
      stimulus-related aspects of gamma-band activity were already evident in the naive
      subjects, aspects related to successful target-discrimination only emerged with
      learning. Frequency-modulated tones were employed as stimuli and were varied with
      respect to two stimulus dimensions, viz. "spectral content" and "modulation
      direction". A target stimulus had to be discriminated in a GO/(NO-GO) paradigm
      from three non-target stimuli matching the target in only one or none of these
      dimensions. Analysis of the event-related potentials indicated that the physical
      stimulus parameters explained most of the variance in amplitude of most event
      related potential components. For the evoked gamma-band activity no learning
      related modulations were found. The induced gamma-band activity showed a
      relationship with the similarity of a stimulus with the target that was most
      prominent in the right hemisphere. The correspondence between task-specific
      behavior and the amplitude of induced gamma-band activity, both developing with
      learning, supports a functional relevance of this form of oscillation beyond
      merely processing physical stimulus attributes.

PMID- 18053971
TI  - Subject's own name as a novel in a MMN design: a combined ERP and PET study.
AB  - With a view to elaborating a clinical tool to assess cognitive functions in brain
      damaged patients, we had previously displayed characteristic patterns of ERPs (32
      electrodes) in awake healthy persons in response to their own name (SON)
      presented as a novel in a passive oddball paradigm. In the present combined ERP
      and PET study, in an attempt to identify brain correlates of duration MMN and
      response to SON uttered by a familiar (FV) or an unknown voice (NFV), we used a
      block design protocol as close as possible to the aforementioned SON protocol.
      ERP data showed robust duration MMN and novelty P3 in response to SON similar to
      our previous results. The PET technique did not allow true MMN generators to be
      disclosed, but blocks with duration deviants elicited an increase of activation
      in the right temporal pole as compared with the control condition with no
      deviants, supporting the hypothesis of right hemispheric dominance in early sound
      discrimination. For SON contrasts, robust cerebral blood flow activation present
      over temporal, frontal and parietal cortices, in the hippocampus and in the
      precuneus could be associated with speech, novelty and self-recognition
      processing. Familiar and unfamiliar voices activated the prefrontal cortex
      differently, suggesting different retrieval processes, although corresponding ERP
      responses could not be differentiated.

PMID- 18053972
TI  - Prenatal exposure to nicotine with associated in utero hypoxia decreased fetal
      brain muscarinic mRNA in the rat.
AB  - Prenatal exposure to nicotine can be associated with fetal abnormal development
      and brain damage. This study determined the effect of administration of nicotine
      with associated in utero hypoxia in maternal rats from early, middle, and late
      gestation on fetal blood hemoglobin, and expression of cholinergic receptor
      subtypes in the fetal brain. Our results demonstrated that maternal subcutaneous
      nicotine from the early gestation increased fetal hemoglobin and hematocrit,
      associated with reduction of PO(2). Although exposure to nicotine during late
      gestation had no effects on fetal brain weight, nicotine administration from the
      early gestation significantly decreased fetal brain muscarinic receptor (M1, M2,
      M3, and M4) mRNA expression, associated with restricted brain growth. Nicotine
      altered muscarinic receptor subtype expression in the fetal forebrain and
      hindbrain showed regional differences. In addition, there were gestational
      differences for fetal brain muscarinic suppression by prenatal nicotine.
      Together, the results demonstrate that nicotine-induced in utero hypoxia is
      associated with poor development of muscarinic receptors in the fetal brain and
      restricted brain growth, and that either prolonged prenatal exposure to nicotine
      or critical "window" period for the brain development during pregnancy may play a
      role in prenatal nicotine-induced fetal muscarinic-receptor deficiency in the
      fetal brain.

PMID- 18053970
TI  - Mouse strain differences in the effects of corticotropin releasing hormone (CRH)
      on sleep and wakefulness.
AB  - Corticotropin releasing hormone (CRH) plays a major role in central nervous
      system responses to stressors and has been implicated in stress-induced
      alterations in sleep. In the absence of stressors, CRH contributes to the
      regulation of spontaneous waking. We examined the effects of CRH and astressin
      (AST), a non-specific CRH antagonist, on wakefulness and sleep in two mouse
      strains with differential responsiveness to stress to determine whether CRH might
      also differentially affect undisturbed sleep and activity. Less reactive C57BL/6J
      (n=7) and high reactive BALB/cJ (n=7) male mice were implanted with a transmitter
      for determining sleep via telemetry and with a guide cannula aimed into a lateral
      ventricle. After recovery from surgery and habituation to handling, ICV
      microinjections of CRH (0.04, 0.2, and 0.4 microg), AST (0.1, 0.4, and 1.0
      microg) or vehicle alone (pyrogen-free saline, 0.2 microl) were administered
      during the fourth hour after lights on and sleep was recorded for the subsequent
      8 h. Comparisons of wakefulness and sleep were conducted across conditions and
      across strains. In C57BL/6J mice, REM was significantly decreased after
      microinjections of CRH (0.2 microg) and CRH (0.4 microg), and NREM and total
      sleep were decreased after microinjections of CRH (0.4 microg). CRH (0.04 microg)
      and AST did not significantly change wakefulness or sleep. In BALB/cJ mice, CRH
      (0.4 microg) increased wakefulness and decreased NREM, REM and total sleep. AST
      decreased active wakefulness and significantly increased REM at the low and high
      dosages. These findings demonstrate that CRH produces changes in arousal when
      given to otherwise undisturbed mice. Strain differences in the effects of CRH and
      AST may be linked to the relative responsiveness of C57BL/6J and BALB/cJ mice to
      stressors and to underlying differences in the CRH system.

PMID- 18053973
TI  - Oxidative-induced apoptosis to an immortalized ganglion cell line is caspase
      independent but involves the activation of poly(ADP-ribose)polymerase and
      apoptosis-inducing factor.
AB  - The aim of the present work was to characterize the molecular basis of oxidative
      induced death, a process that has been implicated in eye diseases like glaucoma,
      in RGC-5 cells, an immortalized retinal ganglion cell (RGC) line. Oxidative
      stress was induced by treatment of RGC-5 cells with hydrogen peroxide and
      compared to a known effect of a light insult (1000 lx, 400-760 nm). Hydrogen
      peroxide causes a loss of viability of RGC-5 cells in a dose-dependent manner.
      Loss of cell viability was by apoptosis characterized by breakdown of DNA (TUNEL
      method), presence of membrane phosphatidylserine (APOPercentage method),
      activation of PARP-1 and AIF. Oxidative stress caused a stimulation of ROS which
      reached maximum levels before optimum apoptosis. Hydrogen-peroxide-induced
      apoptosis did not result in an activation of caspase-3 and was unaffected by the
      caspase inhibitor Z-VAD-fmk. However, the PARP-1 inhibitor NU-1025 counteracted
      the effects of hydrogen peroxide and light. Evidence is provided to show that
      both forms of oxidative stress caused AIF to be cleaved with the product located
      to the cytosolic compartment. Light-induced apoptosis was attenuated by the
      presence of the mitochondrial uncoupler M3778 but potentiated by the presence of
      cobalt. In contrast, hydrogen-peroxide-induced apoptosis was unaffected by M3778
      but attenuated by cobalt. The results show that oxidative stress caused by light
      is dependent on functional mitochondria and that the molecular mechanisms of
      apoptosis caused by hydrogen peroxide or light are similar but not identical.

PMID- 18053974
TI  - ERP--correlates of response selection in a response conflict paradigm.
AB  - Neuroimaging and electrophysiological studies suggest that the anterior cingulate
      cortex (ACC) is involved in the cognitive control of response related action. A
      frontocentral negative ERP-component, the N2, which probably originates from the
      ACC, is usually enhanced in conflict-trials that demand an unexpected response.
      We here used stepped adjustment of response expectation in a response-cueing
      task, and measured how the N2 varied with global and local cue validity. Results
      showed that, irrespective of the current cue validity, response times, error
      rates, and the frontocentral components P2, N2 and P3 increased in unexpected
      trials. Nevertheless, a N2 was also seen in expected trials, and its latency
      correlated positively with reaction times, indicating that this potential does
      not express response conflict only. In line with roles suggested for the ACC, we
      here propose that the N2 is related to the process of response selection which
      influences subsequent processing stages reflected in the P3. Unexpected revisions
      of response programs enhance and delay the N2.

PMID- 18053975
TI  - Profile of glutamate uptake and cellular viability in hippocampal slices exposed
      to oxygen and glucose deprivation: developmental aspects and protection by
      guanosine.
AB  - Stroke syndromes are a major cause of disability in middle and later life
      resulting in severe neuronal degeneration and loss of brain functions. In
      situations with energy failure, glutamate transport is impaired and high levels
      of this amino acid accumulate on the synaptic cleft. Our group has showed that
      guanosine exerts neuroprotection against neurotoxicity situations. The aim of
      this work is draw a post-ischemic profile of glutamate uptake and cell damage
      using an oxygen and glucose deprivation model (OGD) in hippocampal slices from
      young (P10) and adult (P60) rats, analyzing guanosine effect. OGD decreases
      glutamate uptake in both ages and recovery times, although decrease in cell
      viability was only observed 1 and 3 h after OGD in young and adult animals,
      respectively. Guanosine partially protected cell damage from 1 h in P10 and at 3
      h in P60 rats and avoided glutamate uptake decrease from P10 rats at 3 h. The
      impairment of glutamate transporters since immediately after the insult observed
      here is probably due to an energetic failure; loss of cell viability was only
      observed from 1 h after OGD. The mechanism by which guanosine acts in the
      'ischemic' model used here is still unknown, but evidence leads to its
      antiapoptotic effect.

PMID- 18053976
TI  - Modulation of P450 enzymes by Cuban natural products rich in polyphenolic
      compounds in rat hepatocytes.
AB  - This paper reports cytotoxic effects and changes in the P450 system after
      exposing rat hepatocytes to four polyphenol-rich products widely used in Cuban
      traditional medicine (Mangifera indica L. (MSBE), Thalassia testudinum (Tt),
      Erythroxylum minutifolium and confusum extracts). Effects of mangiferin, the main
      polyphenol in MSBE, were also evaluated. Cytotoxicity was assayed by the MTT test
      after exposure of cells to the products (50-1000 microg/mL) for 24 or 72 h. The
      results showed that 500 microg/mL MSBE was moderately cytotoxic after 72 h, while
      mangiferin was not. Marked reductions in cell viability were produced by
      Erythroxylum extracts at concentrations > or = 200 microg/mL, whereas only
      moderate effects were induced by 1000 microg/mL Tt. Seven specific P450
      activities were evaluated after 48 h exposure of cells to the products. MSBE
      reduced phenacetin O-deethylation (POD; CYP1A2) activity in a concentration
      dependent manner (IC(50)=190 microg/mL). No decreases were observed in other
      activities. In contrast, mangiferin produced reductions in five P450 activities:
      IC(50) values of 132, 194, >200, 151 and 137 microg/ml for POD (CYP1A2),
      midazolam 1'-hydroxylation (M1OH; CYP3A1), diclofenac 4'-hydroxylation (D4OH;
      CYP2C6), S-mephenytoin 4'-hydroxylation (SM4OH), and chlorzoxazone 6
      hydroxyaltion (C6OH; CYP2E1), respectively. E. minutifolium, E. confusum and Tt
      extracts produced small reductions in SM4OH and C6OH activities, but no
      significant changes were noted in the other P450 activities. On the other hand,
      all the products increased the benzyloxyresorufin O-debenzylation (BROD; CYP2B1)
      activity, with MSBE, mangiferin or E. minutifolium showing the highest effects
      (about 2-fold over control). Our results showed in vitro effects of these natural
      products on P450 systems, possibly leading to potential metabolic-based
      interactions.

PMID- 18053977
TI  - Assessment of hypolipidaemic activity of three thiazolidin-4-ones in mice given
      high-fat diet and fructose.
AB  - Three 4-thiazolidinones, two with nicotinamide (NAT1 and NAT2) and one with 4
      chlorophenoxyacetamide (PAT1) side chains were evaluated for their
      hypolipidaemic, hypoglycaemic activity in Swiss albino mice fed a high-fat diet
      along with fructose administered in drinking water. NAT1 and PAT caused reduction
      of elevated triglycerides, cholesterol and glucose; NAT2 was effective only
      against triglycerides. Nicotinamide side chain might have contributed to the
      lipid lowering effect of both NAT1 and NAT2, but the bulky group of the latter
      could have affected proper binding to the receptor sites, making it ineffective
      against elevated cholesterol. On the other hand, the 4-chlorophenoxyacetamide
      side chain of PAT might have exerted powerful hypolipidaemic activity, despite
      the bulky substitution at C2. As antioxidants, NAT2 and PAT1 showed superior
      activity, compared to NAT1. The thiazolidinone ring might be responsible for the
      lipid lowering effect, which is however, modified by the type of substitutions at
      C2 and N of the ring. Detailed study is warranted to explain the mechanism of
      action of these compounds as also to make more potent ones.

PMID- 18053978
TI  - Brefeldin A disrupts asymmetric spindle positioning in mouse oocytes.
AB  - Polar body formation in oocytes is an extreme form of asymmetric cell division,
      but what regulates the asymmetric spindle positioning and cytokinesis is poorly
      understood. During mouse oocyte maturation, the metaphase I spindle forms at the
      center but then moves to the cortex prior to anaphase I and first polar body
      emission. We show here that treating denuded mouse oocytes with brefeldin A, an
      inhibitor of Golgi-based membrane fusion, abolished the asymmetric positioning of
      the metaphase I spindle and resulted in the formation of two half-size metaphase
      II eggs, instead of a full-sized egg and a polar body. The normal metaphase II
      spindle is similarly asymmetrically positioned in the mature egg, where the
      spindle lies with its axis parallel to the cortex but becomes perpendicular
      before anaphase II and emission of the second polar body. When ovulated eggs were
      activated with strontium in the presence of brefeldin A, the metaphase II spindle
      failed to assume perpendicular position, and the chromosomes separated without
      the extrusion of the second polar body. Remarkably, symmetric cytokinesis began
      following a 3 h delay, forming two half-size eggs each containing a pronucleus.
      BFA-sensitive intracellular vesicular transport is therefore required for spindle
      positioning in both MI and MII.

PMID- 18053979
TI  - Plasticity of proximal-distal cell fate in the mammalian limb bud.
AB  - Normal morphogenesis depends on location-specific behaviours of cells. There are
      circumstances in the embryo where it would be advantageous for cells to be
      flexible in establishing their fate, such as in the limb bud where some cells
      cross between Homeobox (Hox) expression domains. It is not known how flexible
      cell fate determination is in the embryonic limb bud, nor is the sequence and
      timing of this process clear. By transposing small groups of dye and genetically
      labelled limb bud cells in cultured mouse embryos, we show that mesenchymal cells
      are capable of altering their expression of Hox genes to match that of their
      local environment in response to instructive mesenchymal cues. Plasticity of Hox
      expression wanes during embryogenesis, and is lost earlier in the proximal limb
      bud than distally. These findings are consistent with a model of progressive fate
      determination in a zone that encompasses the entirety of the limb bud mesenchyme,
      and suggest a mechanism for the maintenance of sharp Hox boundaries despite cell
      transit across them.

PMID- 18053980
TI  - Association of urinary cadmium and myocardial infarction.
AB  - We conducted a cross-sectional analysis of individuals 45-79 years old in the
      National Health and Nutrition Examination Survey III (1988-1994) (NHANES III).
      Myocardial infarction was determined by electrocardiogram (ECG). Our sample
      included 4912 participants, which when weighted represented 52,234,055 Americans.
      We performed adjusted logistic regressions with the Framingham risk score, pack
      years of smoking, race-ethnicity, and family history of heart attack, and
      diabetes as covariates. Urinary cadmium >or= 0.88 microg/g creatinine had an odds
      ratio of 1.86 (95% CI 1.26-2.75) compared to urinary cadmium <0.43 microg/g
      creatinine. This result supports the hypothesis that cadmium is associated with
      coronary heart disease. When logistic regressions were done by gender, women, but
      not men, showed a significant association of urinary cadmium with myocardial
      infarction. Women with urinary cadmium >or= 0.88 microg/g creatinine had an odds
      ratio of 1.80 (95% CI 1.06-3.04) compared to urinary cadmium <0.43 microg/g
      creatinine. When the analysis was restricted to never smokers (N=2187) urinary
      cadmium >or= 0.88 microg/g creatinine had an odds ratio of 1.85 (95% CI 1.10
      3.14) compared to urinary cadmium <0.43 microg/g creatinine.

PMID- 18053981
TI  - Age-related differential sensitivity to MK-801-induced locomotion and stereotypy
      in C57BL/6 mice.
AB  - Psychomotor effects elicited by systemic administration of the noncompetitive
      NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 (dizocilpine maleate)
      represent perturbation of glutamatergic pathways, providing an animal model for
      psychotic symptoms of schizophrenia. Hyperlocomotion and stereotypy are the two
      main psychomotor behaviors induced by MK-801. This study compared MK-801-induced
      hyperlocomotion and stereotypy in young (1-month old) and aged mice (12-month
      old), in order to determine how the aging process may influence these behaviors.
      The tested MK-801 doses ranged from 0.015 to 1 mg/kg. The data indicated that MK
      801 impacted the aged mice more pronouncedly than the young mice, as both
      hyperlocomotion and stereotypy were increased significantly more in the aged mice
      relative to the young mice. These results suggest an age-related increase in MK
      801 sensitivity in mice.

PMID- 18053982
TI  - Exogenous melatonin ameliorates hepatic injury in a rat cardiopulmonary bypass
      model.
AB  - Hepatic injury after cardiac surgery was considered to be a consequence of
      cardiopulmonary bypass (CPB). This study tested the hypothesis that melatonin
      could attenuate the hepatic injury in a rat CPB model. Male Sprague-Dawley rats
      were randomly divided into four groups: sham-operation group, control group
      (given an equal volume of vehicle), low dose melatonin (10 mg/kg) treated group
      and high dose melatonin (20 mg/kg) treated group. Blood samples were collected at
      the beginning, at the cessation of CPB, and at 30 min, 1, 2, 3 and 24 h post
      operation. Liver samples were harvested at 24 h after operation. The serum
      indices of the liver enzymes and systemic inflammation, as well as oxidative
      stress indices and the Ca++-ATPase activity of liver tissues were determined. In
      the control animals, the indices of liver enzymes, tumor necrosis factor-alpha
      (TNF-alpha) increased after operation, and liver inducible nitric oxide synthase
      (iNOS), malondialdehyde (MDA), myeloperoxidase (MPO) increased as well. However,
      the activities of liver antioxidative enzymes and the concentration of
      glutathione (GSH) decreased remarkably. Results in melatonin group showed that
      melatonin reversed all the biochemical changes, but there was no significant
      difference between the melatonin-treated groups. In addition, histological
      findings further supported these results. All results indicated that application
      of exogenous melatonin during operation preserves liver function by reducing
      oxidative stress and the systemic inflammatory response.

PMID- 18053983
TI  - Endothelial dysfunction and improvement of the angiotensin II-reactivity in
      hypercholesterolemic rabbits: role of cyclooxygenase metabolites.
AB  - The aim of this paper was to study the effect of high cholesterol diet on
      endothelial function and vascular reactivity to angiotensin II and to test the
      role of vasoconstrictor cyclooxygenase metabolites in this experimental
      condition. Rabbits were fed with either normal chow or a diet containing 1%
      cholesterol for 6-7-week. Isometric contractions were measured in rubbed or
      unrubbed aortic rings. Arteries were contracted with noradrenaline and then
      exposed to one cumulative dose-response curve to acetylcholine in absence
      (control) or in presence of indomethacin, (N-[2-cyvlohexyloxy)-4-nitrophenyl]
      methanesulfonamide) (NS 398) or 4-hydroxy-2,2,6,6-tetraethylpiperidine-N-oxyl
      (tempol). After washing the arteries, one cumulative dose-response curve to
      angiotensin II was constructed in absence or presence of indomethacin, NS 398,
      [1S-[1 alpha,2 beta (5Z),3 beta,4 alpha]-7-[3-[[2-[(phenylamino)
      carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1] hept-2-yl]-5-heptenoic acid
      (SQ29548) or 17-octadecynoic acid (17-ODYA). In other group, resting potential
      was recorded in basal and angiotensin II-stimulated conditions. Indomethacin, NS
      398 or 17-ODYA were added to the bath before angiotensin II-stimulation. Rabbits
      fed on a diet enriched with cholesterol showed higher plasma levels of total
      cholesterol and LDL. Hypercholesterolemic diet impaired acetylcholine relaxation.
      Indomethacin normalized endothelium-dependent relaxation whereas NS 398 and
      tempol had no effect on this phenomenon. Angiotensin II-reactivity was increased
      in endothelium intact hypercholesterolemic aortic rings and indomethacin, SQ29548
      or 17-ODYA blocked this effect. The resting potential of unrubbed
      hypercholesterolemic arteries was significantly less negative to control after
      angiotensin II-stimulation. 17-ODYA but not indomethacin prevented angiotensin II
      depolarization. High cholesterol diet caused endothelial dysfunction and
      increased the angiotensin II-reactivity. Both effects were cyclooxygenase1
      dependent. Deficit in the NO-production might improve 20-hydroxyeicosatrienoic
      acid availability, which induces depolarization and angiotensin II-sensitization.
      In addition, 20-hydroxyeicosatrienoic acid would be metabolized by
      cyclooxygenase1 to 20-endoperoxides which act through thromboxane
      A(2)/prostaglandin H(2) receptors contributing to angiotensin II-reactivity
      increase.

PMID- 18053984
TI  - The dynamics of pre-mRNAs and poly(A)+ RNA at speckles in living cells revealed
      by iFRAP studies.
AB  - Speckles are subnuclear domains where pre-mRNA splicing factors accumulate in the
      interchromatin space. To investigate the dynamics of mRNAs at speckles,
      fluorescently labeled Drosophila Fushitarazu (ftz) pre-mRNAs were microinjected
      into the nuclei of Cos7 cells and the dissociation kinetics of pre-mRNAs from
      speckles was analyzed using photobleaching techniques. The microinjected ftz pre
      mRNAs accumulated in speckles in an intron-dependent manner and were spliced and
      exported to the cytoplasm with a half-time of about 10 min. Dissociation of the
      accumulated pre-mRNAs in speckles exhibited rapid diffusion and slow-dissociation
      of about 100 s. The slow-dissociation required metabolic energy of ATP. Two types
      of splice-defective mutated mRNAs dissociated from the speckle with a time
      constant similar to that of wild-type mRNA, indicating that slow-dissociation was
      not coupled to the splicing reaction. Furthermore, some pre-mRNAs shuttled
      between speckles and nucleoplasm, suggesting that pre-mRNAs repeatedly associated
      with and dissociated from speckles until introns were removed. Next, endogenous
      poly(A)+ RNA was visualized by injecting Cy3-labeled 2'O-methyl oligo(U)22
      probes. Some poly(A)+ RNA distributed diffusely within the nucleus, but some of
      them accumulated in speckles and dissociated at time constant of about 100 s.

PMID- 18053985
TI  - Interactions of myeloma cells with osteoclasts promote tumour expansion and bone
      degradation through activation of a complex signalling network and upregulation
      of cathepsin K, matrix metalloproteinases (MMPs) and urokinase plasminogen
      activator (uPA).
AB  - Bone destruction is one of the most debilitating manifestations of multiple
      myeloma (MM) and results from the interaction of myeloma cells with the bone
      marrow microenvironment. Within the bone marrow, the disturbed balance between
      osteoclasts and osteoblasts is important for the development of lytic lesions.
      However, the mechanisms behind myeloma-mediated bone destruction are not
      completely understood. In order to address the importance of myeloma cell
      osteoclast interactions in MM pathogenesis, we have developed a functional
      coculture system. We found that myeloma-osteoclast interactions resulted in
      stimulation of myeloma cell growth and osteoclastic activity through activation
      of major signalling pathways and upregulation of proteases. Signals from
      osteoclasts activated the p44/p42 MAPK, STAT3 and PI3K/Akt pathways in myeloma
      cells. In turn, myeloma cells triggered p38 MAPK and NF-kappaB signalling in
      osteoclasts. Myeloma-osteoclast interactions stimulated the production of TRAP,
      cathepsin K, matrix metalloproteinase (MMP)-1, -9, and urokinase plasminogen
      activator (uPA). Consistent data with myeloma cell lines and primary myeloma
      cells underlined the biological relevance of these findings. In conclusion, we
      demonstrated the critical role of myeloma cell-osteoclast interactions in the
      existing interdependence between tumour expansion and bone disease. The
      identified molecular events might provide the rationale for novel treatment
      strategies.

PMID- 18053987
TI  - Characterization of the striatal 6-OHDA model of Parkinson's disease in wild type
      and alpha-synuclein-deleted mice.
AB  - Genetically modified mice models are increasingly used to study the
      pathophysiology of Parkinson's disease (PD), particularly in conditions where
      they are subjected to toxins specific for dopaminergic neurons. The most widely
      used toxin in these paradigms is 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP), although it presents a number of drawbacks regarding (i) the kinetics of
      neurodegeneration, (ii) strain-specificity and (iii) partial lesion recovery. 6
      hydroxydopamine (6-OHDA) may be an alternative tool since it leads to a partial
      damage of DA terminals and to a delayed and progressive loss of nigral DA
      neurons. It is frequently used in rats and well characterized in this species. In
      mice, however, this model has not been described in detail to date. The aim of
      the present study was to characterize the time course of intra-striatal 6-OHDA
      lesions in mice with regard to i) dopaminergic cell loss, ii) dopamine
      concentrations in the substantia nigra and the striatum, iii) hydroxylation
      products in substantia nigra and striatum and iv) behavioural impairment.
      Furthermore, we used alpha-synuclein-deleted mice, which have been studied
      extensively in MPTP paradigms, and examined their reactivity to intra-striatal 6
      OHDA injections. Intra-striatally injected 6-OHDA leads to a long-lasting
      dopamine depletion of the nigro-striatal pathway, whereas behavioural parameters
      partially recovered over a two month period. Its toxicity seems to be influenced
      by alpha-synuclein, since alpha-synuclein-deleted mice are more resistant against
      6-OHDA than their wild type littermates. In summary, we propose that the striatal
      6-OHDA model may be a valuable addition and/or alternative in genetically
      modified mice models used in the study of PD pathophysiology.

PMID- 18053986
TI  - Enhancing trabecular outflow by disrupting the actin cytoskeleton, increasing
      uveoscleral outflow with prostaglandins, and understanding the pathophysiology of
      presbyopia interrogating Mother Nature: asking why, asking how, recognizing the
      signs, following the trail.
AB  - Several major areas of work by the author and his international collaborators are
      reviewed. (1) The ciliary muscle in the non-human primate eye was disinserted at
      the scleral spur. Pilocarpine was then ineffective in increasing outflow
      facility, indicating that ciliary muscle contraction mediated the IOP-lowering
      effect of muscarinic cholinergics. (2) Compounds such as cytochalasins, H-7 and
      latrunculin A/B, which alter the actin cytoskeleton, cellular contractility and
      cellular adhesions in cultured trabecular meshwork cells, relaxed trabecular
      pathway cells and consequently the meshwork itself so as to decrease IOP and
      enhance trabecular outflow facility in non-human primates. Gene transfer
      approaches utilizing C3 and caldesmon over-expression by viral vectors to target
      specific steps in the cellular contractility/cytoskeleton/cell adhesion cascades
      characteristically altered trabecular meshwork cell morphology and increased
      outflow facility in organ-cultured anterior segments. (3) Prostaglandin F(2alpha)
      analogues enhanced matrix metalloproteinase production by ciliary muscle cells
      and scleral fibroblasts, leading to remodeling of the extracellular matrix of the
      ciliary muscle and sclera and consequently to increased uveoscleral outflow and
      decreased IOP in primates. (4) The rhesus monkey was an excellent model for human
      presbyopia, losing the accommodative response to cholinergic stimulation in the
      same timeframe relative to lifespan. No changes were found in ciliary muscle
      enzymes involved in acetylcholine biosynthesis or degradation or in muscarinic
      receptor numbers or affinity. Contractility of isolated ciliary muscle did not
      diminish with age, but posterior ciliary muscle attachments stiffened, suggesting
      a possible role in restricting muscle and consequently lens movement during
      accommodation. A model to reproducibly stimulate accommodation through central
      stimulation of the Edinger-Westphal nucleus was developed. Goniovideography and
      ultrasound biomicroscopic techniques allowed real-time recording and analysis of
      the accommodation-relevant structures. Surgical ablation of the intraocular
      structures involved in the accommodation response has led to further
      understanding of their roles and changes with age related to presbyopia. (5)
      Global collaborations such as those involved in these studies will be essential
      in the future, as science becomes "bigger".

PMID- 18053988
TI  - Abeta(1-42) injection causes memory impairment, lowered cortical and serum BDNF
      levels, and decreased hippocampal 5-HT(2A) levels.
AB  - Aggregation of the beta-amyloid protein (Abeta) is a hallmark of Alzheimer's
      disease (AD) and is believed to be causally involved in a neurodegenerative
      cascade. In patients with AD, reduced levels of serum Brain Derived Neurotrophic
      Factor (BDNF) and cortical 5-HT(2A) receptor binding has recently been reported
      but it is unknown how these changes are related to beta-amyloid accumulation. In
      this study we examined in rats the effect of intrahippocampal injections of
      aggregated Abeta(1-42) (1 microg/microl) on serum and brain BDNF or 5-HT(2A)
      receptor levels. A social recognition test paradigm was used to monitor Abeta(1
      42) induced memory impairment. Memory impairment was seen 22 days after injection
      of Abeta(1-42) in the experimental group and until termination of the
      experiments. In the Abeta(1-42) injected animals we saw an abolished increase in
      serum BDNF levels that was accompanied by significant lower BDNF levels in
      frontal cortex and by an 8.5% reduction in hippocampal 5-HT(2A) receptor levels.
      A tendency towards lowered cortical 5-HT(2A) was also observed. These results
      indicate that the Abeta(1-42) associated memory deficit is associated with an
      impaired BDNF regulation, which is reflected in lower cortical BDNF levels, and
      changes in hippocampal 5-HT(2A) receptor levels. This suggests that the BDNF and
      5-HT2A changes observed in AD are related to the presence of Abeta(1-42)
      deposits.

PMID- 18053989
TI  - Expression and localization of Kv1 potassium channels in rat dorsal and ventral
      spinal roots.
AB  - We investigated the expression and localization of Kv1 channels in dorsal spinal
      roots (DRs) and ventral spinal roots (VRs) in rats. Among Kv1.1-1.6 tested by RT
      PCR, mRNAs of Kv1.1, 1.2, and 1.5 were moderately expressed, those of Kv1.3 and
      Kv1.6 were weakly expressed, and that of Kv1.4 was hardly expressed at all in
      both DRs and VRs, whereas all six mRNAs were detected in spinal cord. Western
      blotting revealed that the major immunoreactive proteins were Kv1.1 and Kv1.2 in
      both DRs and VRs. Quantitative analysis indicated that levels of Kv1.1 and Kv1.2
      protein were significantly higher in DRs than VRs. Immunohistochemical
      examination showed that Kv1.1 and Kv1.2 were colocalized in juxtaparanodal
      regions of axons in both DRs and VRs. Finally, immunoprecipitation experiments
      revealed that Kv1.1 and Kv1.2 were coassembled. These findings indicate that Kv1
      subtypes in DRs and VRs are somewhat different from those in spinal cord, and
      that the numbers of Kv1.1 and Kv1.2 channels are higher in DRs than VRs.

PMID- 18053990
TI  - Amyloid beta peptides and glutamatergic synaptic dysregulation.
AB  - Alzheimer's disease (AD) is a major neurodegenerative disorder in which
      overproduction and accumulation of amyloid beta (Abeta) peptides result in
      synaptic dysfunction. Recent reports strongly suggest that in the initial stages
      of AD glutamate receptors are dysregulated by Abeta accumulation resulting in
      disruption of glutamatergic synaptic transmission which parallels early cognitive
      deficits. In the presence of Abeta, 2-amino-3-(3-hydoxy-5-methylisoxazol-4-yl)
      propionic acid (AMPA) glutamate receptor function is disrupted and the surface
      expression is reduced. Abeta has also been shown to modulate N-methyl-d-aspartate
      receptors (NMDARs) and metabotropic glutamate receptors. The Abeta mediated
      glutamate receptor modifications can lead to synaptic dysfunction resulting in
      excitotoxic neurodegeneration during the progression of AD. This review discusses
      the recent findings that glutamatergic signaling could be compromised by Abeta
      induced modulation of synaptic glutamate receptors in specific brain regions.

PMID- 18053991
TI  - Effects of Fasciola gigantica experimental infection on some inorganic elements
      in the snail host Lymnaea natalensis.
AB  - Flame atomic absorption spectrometry was performed to determine the alteration in
      the concentrations of metallic ion Pb, Zn, K, Na, Fe, Cu and Co in the soft parts
      of the Lymnaea natalensis snails shedding Fasciola gigantica cercariae and to
      determine the alteration in the concentration of Ca in the soft parts and shells
      of the same snails. The Co was found to be present at concentration level below
      the detection limits of the analytical method used. Regarding detected elements,
      three elements Zn, K and Cu were found to be present at significantly higher
      concentrations in cercariae-shedding snails compared with uninfected snails. Two
      elements, Pb and Na, showed significant decrease in cercariae-shedding snails
      compared to uninfected ones. The concentration of Fe showed non-significant
      increase. The results showed significant lowering in the calcium content of the
      shells and soft parts of cercariae-shedding snails relative to the calcium
      content in the uninfected ones. The obtained results and the hypothesis of
      hypercalcification in shells of infected snails were discussed.

PMID- 18053992
TI  - Plasmodium falciparum: sequence analysis of the gene encoding the C-terminus
      region of the merozoite surface protein-1, a potential malaria vaccine antigen,
      in Iranian clinical isolates.
AB  - C-terminal region of merozoite surface protein-1 of Plasmodium falciparum (PfMSP
      1) isolated from different parts of the world revealed sequence variability,
      however no data exist on sequence heterogeneity of this region from Iran. To
      address this question, DNA encoding the carboxyl (C)-terminal region of PfMSP-1
      was amplified in 144 Iranian P. falciparum clinical isolates, using allele type
      specific primers. In this study both MAD20 (88.2%) and K1 (7.6%) types were
      detected. Sequence analysis of 33 and 92 fragments corresponding to pfmsp-1(42)
      and pfmsp-1(19) revealed eight (15MAD1-15MAD7 and 15KCH) and five [A1 (E/TSR/L),
      A2 (Q/KNG/F), A3 (E/KNG/F), A4 (E/TSG/L), and A5 (Q/KNG/L)] distinct haplotypes,
      respectively. E/TSG/L variant type was the predominant haplotype, and reported
      only from Thailand and India, but E/KNG/L is widespread in Africa, Asia, and
      Latin America; but not found among Iranian isolates. In summary, result of this
      study indicates limited antigenic diversity, and thus support the potential
      utility of the C-terminal region of PfMSP-1 in designing polyvalent vaccine
      constructs.

PMID- 18053993
TI  - Expression of cyclooxygenase-2 and vascular endothelial growth factor in ovarian
      endometriotic cysts and their relationship with angiogenesis.
AB  - OBJECTIVE: To investigate the expression of cyclooxygenase-2 (Cox-2) and vascular
      endothelial growth factor (VEGF) in ovarian endometriotic cysts and assess their
      relation with angiogenesis. DESIGN: Experimental clinical study. SETTING:
      University hospital. PATIENT(S): Fifty patients with ovarian endometriotic cysts.
      INTERVENTION(S): Surgical excision of 50 ovarian endometriotic cysts. MAIN
      OUTCOME MEASURE(S): Microvessel density and the expression of Cox-2 and VEGF were
      analyzed immunohistochemically. RESULT(S): Cyclooxygenase-2 immunoreactivity was
      mainly cytoplasmic in glandular epithelial cells in all of the ovarian
      endometriotic cysts, with low expression in 12 cases (24%), moderate expression
      in 21 (42%), and high expression in 17 (34%). Vascular endothelial growth factor
      immunoreactivity was mainly cytoplasmic in stromal cells in 46 (92%) of the
      ovarian endometriotic cysts, with low expression in 12 cases (24%), moderate
      expression in 18 (36%), and high expression in 16 (32%). No immunoreactivity was
      present in 4 cases (8%). Both Cox-2 (r = 0.728) and VEGF (r = 0.670) were
      closely, statistically significantly related with microvessel density in ovarian
      endometriotic cysts. Cyclooxygenase-2 and VEGF also were highly statistically
      significantly correlated (r = 0.777) with each other. CONCLUSION(S): We observed
      Cox-2 expression mostly in glandular epithelial cells of ovarian endometriotic
      cysts, whereas VEGF expression was observed mainly in stromal cells.
      Cyclooxygenase-2 and VEGF were closely correlated with each other, and both of
      them appear to play a role in the angiogenesis of ovarian endometriosis.

PMID- 18053994
TI  - Attitudes of couples with stored frozen embryos toward conditional embryo
      donation.
AB  - OBJECTIVE: To survey clients with stored frozen embryos regarding intention to
      donate embryos to other couples and attitudes toward conditional donation.
      DESIGN: Anonymous postal questionnaire. SETTING: A private IVF clinic in Sydney,
      Australia. PATIENT(S): Clients with embryos stored for 3 or more years.
      INTERVENTION(S): Patients completed a survey regarding attitudes to embryo
      donation and conditional embryo donation. Spontaneous written comments were also
      analyzed. MAIN OUTCOME MEASURE(S): Intentions regarding embryos, attitudes toward
      conditional donation, extent to which conditional donation would influence
      decision-making. RESULT(S): Of the clients surveyed, 99 women (35%) and 66 men
      (23%) responded. Only 4% indicated it was likely they would donate to other
      couples; 48% thought donors should be able to specify characteristics of
      recipients; and 41% indicated they would be more likely to donate if donation was
      conditional. A sense of ownership and responsibility for the well-being of the
      offspring underpinned reluctance to donate. Perceived control over the caretaking
      environment was seen as an advantage of conditional donation. Concerns were also
      raised about the need for donors to relinquish control and the potential for
      discrimination. CONCLUSION(S): An empirical understanding of the views of
      infertility patients regarding stored embryos is critical to informing public
      discourse, policy debates, and clinical practice as well as counseling, policy,
      and protocols on embryo donation.

PMID- 18053995
TI  - A comparison of the efficacy, tolerability, and convenience of two formulations
      of follitropin-alpha in Iranian woman undergoing intracytoplasmic sperm injection
      cycles.
AB  - OBJECTIVE: To compare the efficacy, tolerability, and convenience of two
      formulations of the follitropin-alpha (Gonal-f) pen device versus the
      conventional form in Iranian women undergoing ovarian stimulation for
      intracytoplasmic sperm injection. DESIGN: Randomized, single-center trial,
      parallel-group, single blind. SETTING: Tertiary referral center, University
      Hospital. PATIENT(S): A total of 100 patients undergoing intracytoplasmic sperm
      injection. INTERVENTION(S): After down-regulation with busereline acetate,
      patients were randomized to receive the pen device or the conventional syringe of
      follitropin-alpha. A computer-generated randomization list was used to allocate
      the patients to one of these two groups. MAIN OUTCOME MEASURE(S): The primary
      outcomes were patients' satisfaction, convenience, occurrence of local tolerance
      symptoms, and pain. Total dose of follitropin-alpha, duration of follitropin
      alpha treatment, number of oocyte retrieved, number of viable embryos, and
      clinical pregnancies were secondary outcome measures. Data collection was
      performed by means of a questionnaire designed for the purpose of this study. The
      pain scored according to the Visual Analogue Scale. RESULT(S): Self
      administration and patients' satisfaction were significantly higher in the pen
      device group than the conventional syringe group. Local reactions at injection
      sites and pain were significantly higher in the conventional syringe group than
      in the pen device group. There were no statistically differences in secondary
      outcome measures and convenience between two groups. CONCLUSION(S): Among the
      Iranian patients that we studied, the pen device of Gonal-f is safe, convenient,
      and less painful, with more patients' satisfaction than the conventional syringe
      form, but both forms have equal efficacy in intracytoplasmic sperm injection
      cycles.

PMID- 18053996
TI  - Bladder hematoma after vaginal paracentesis.
AB  - Puncture of the bladder wall with a 17-gauge needle is usually safe; however, in
      the patient on anticoagulation, inadvertent puncture of the bladder could result
      in bladder hematoma formation.

PMID- 18053997
TI  - Dietary trans fatty acid intake is associated with increased fetal loss.
AB  - OBJECTIVE: To examine whether dietary trans fatty acids (TFAs) were associated
      with fetal loss (no. of pregnancies - no. of live births). The basis of our
      inquiry derives from the facts that the PPAR-gamma receptor plays a pivotal role
      in placental function and that TFAs down-regulate PPAR-gamma gene mRNA
      expression. DESIGN: Retrospective study comparing dietary data on TFAs and total
      calories from Block 98 quantitative food frequency questionnaire on 104 women
      with insulin data and reporting one or more pregnancies. SETTING: Twenty-five- to
      30-year follow-up as young adults (age 39.5 +/- 4.5 years) of schoolgirls in the
      Princeton School cardiovascular risk study. PATIENT(S): Former participants in
      school-based research program at ages 6-18 years (1973-78), screened as part of
      follow-up study (1998-2003). MAIN OUTCOME MEASURE(S): Fetal loss. RESULT(S): By
      stepwise logistic regression, with fetal loss (>or=1 vs. 0) as the dependent
      variable and total calories, percent calories from TFAs (linear and squared
      terms), diabetes (yes/no), serum insulin, age, race, body mass index, leisure and
      work physical activity, and education as explanatory variables, percent calories
      from TFAs was positively, curvilinearly, independently associated with fetal
      loss. For each 1-unit increase in the squared term of percent calories from TFAs,
      the odds of having fetal loss versus no fetal loss increased 1.106 times (odds
      ratio = 1.106; 95% confidence interval 1.026-1.192). CONCLUSION(S): Since PPAR
      gamma plays a pivotal role in placental biology and is down-regulated by TFAs,
      TFAs may be a reversible risk factor for fetal loss.

PMID- 18053998
TI  - Randomized, multicenter, double-blind, placebo-controlled trial to evaluate the
      efficacy and safety of synthetic conjugated estrogens B for the treatment of
      vulvovaginal atrophy in healthy postmenopausal women.
AB  - OBJECTIVE: To evaluate the safety and efficacy of synthetic conjugated estrogens
      B (SCE-B; 0.3 mg/d) for 12 weeks in the treatment of vulvovaginal atrophy in
      symptomatic, postmenopausal women. DESIGN: Prospective, randomized, multicenter,
      double-blind, placebo-controlled trial. SETTING: Forty-two participating sites in
      the United States. PATIENT(S): Postmenopausal women with at least one moderate to
      severe symptom of vaginal atrophy. INTERVENTION(S): Daily oral administration, in
      a randomized, placebo-controlled setting, of SCE-B (0.3 mg) or of placebo for 12
      weeks. MAIN OUTCOME MEASURE(S): Mean changes in vaginal maturation index,
      percentage of parabasal and superficial cells, vaginal pH, and severity of the
      most bothersome symptom (MBS) between baseline and predetermined time points were
      assessed. Safety and tolerability were evaluated. RESULT(S): A total of 310 women
      (mean age, 58.6 y) were enrolled. Synthetic conjugated estrogens B yielded
      statistically significantly greater differences in vaginal maturation index and
      vaginal pH from baseline to the end of treatment. Vaginal dryness (44.4%) and
      pain during intercourse (30.2%) were the symptoms most commonly identified as the
      MBS. A statistically significant mean reduction in the severity of the MBS was
      noted for SCE-B. There were no clinically significant differences observed
      between the two groups for findings related to safety. CONCLUSION(S): Synthetic
      conjugated estrogens B (0.3 mg/d) was effective in treating vulvovaginal atrophy
      in symptomatic postmenopausal women. Significant improvement was seen in vaginal
      maturation index, vaginal pH, and severity of MBS from baseline to the end of
      treatment.

PMID- 18053999
TI  - Effects of androgen on embryo implantation in the mouse delayed-implantation
      model.
AB  - OBJECTIVE: To examine the effects of androgen on implantation and decidualization
      in the mouse delayed-implantation model. DESIGN: Experimental animal study.
      SETTING: University research laboratory. ANIMAL(S): Sexually mature female mice
      (Kunming White strain). INTERVENTION(S): Delayed and activated implantation;
      pseudopregnancy; embryo transfer (ET); E(2) assay; inhibitor. MAIN OUTCOME
      MEASURE(S): Effects of androgen on embryo implantation were determined by
      treating the mice under delayed implantation with different doses of testosterone
      propionate (TP); the effects of androgen on the expression of implantation
      related genes were examined by in situ hybridization. RESULT(S): Delayed
      implantation could be initiated by TP. Dihydrotestosterone was also able to
      initiate implantation in the delayed-implantation model. The implantation window
      could be maintained for at least 48 hours by 5 mg TP per mouse. Prostaglandin
      endoperoxide synthase 2 (Ptgs2) and microsomal prostaglandin E synthase (mPtges)
      were aberrantly expressed in mouse uterus at implantation sites after delayed
      implantation was activated by high doses of TP. CONCLUSION(S): A low dose of TP
      led to a delay in embryo implantation, but a high dose caused aberrant expression
      of both Ptgs2 and mPtges at the implantation site. It is possible that high doses
      of TP may disturb peri-implantation development or may be involved in early
      pregnancy loss by disturbing the uterine prostaglandin system.

PMID- 18054000
TI  - A prospective randomized controlled trial comparing two embryo transfer catheters
      in an ART program.
AB  - OBJECTIVE: To compare the performance of the Cook Sydney IVF (SIVF) embryo
      transfer (ET) catheter and the Edwards-Wallace (EW) ET catheter. DESIGN:
      Prospective randomized controlled clinical trial with an intention-to-treat
      analysis. SETTING: Two-center study. PATIENT(S): Four hundred consecutive women
      <40 years undergoing ET with two fresh embryos. INTERVENTION(S): Women were
      randomly allocated to undergo ET with either the EW or the SIVF catheter, with
      possible catheter change in case of insertion difficulties. MAIN OUTCOME
      MEASURE(S): Live birth and clinical pregnancy rates. RESULT(S): Two hundred two
      women were allocated to the SIVF catheter and 198 to the EW catheter. No
      significant differences in the clinical pregnancy rates (odds ratio [OR] 0.99,
      95% confidence interval [CI] 0.66-1.47) and live-birth rates (OR 1.09, 95% CI
      0.72-1.65) were found. The EW catheter had to be changed more often than the SIVF
      catheter (OR 9.5, 95% CI 3.3-27.5) because of catheter insertion problems.
      CONCLUSION(S): The pregnancy and live birth rates were not significantly
      different with the two catheters, but catheter insertion failure was
      significantly more common with the EW catheter than with the SIVF catheter.

PMID- 18054001
TI  - Relationship between time of reperfusion and E-selectin expression, neutrophil
      recruitment, and germ cell apoptosis after testicular ischemia in a rat model.
AB  - OBJECTIVE: To examine the relationship between the time of reperfusion and
      neutrophil recruitment, E-selectin expression, and germ cell apoptosis in the
      ischemic and contralateral testis after testicular ischemia-reperfusion (IR)
      injury in a rat. DESIGN: Laboratory study. SETTING: Research laboratory in a
      faculty of medicine at Technion-institute of technology in Israel. ANIMAL(S):
      Sixty adult Sprague-Dawley rats weighing 250-280 g. INTERVENTION(S): Testicular
      IR. MAIN OUTCOME MEASURE(S): Testicular germ cell apoptosis was assessed by
      terminal deoxynucleotide transferase-mediated 2'-deoxyuridine 5'-triphosphate
      nick-end labeling immunohistochemical assay, using an in situ cell death
      detection kit. The recruitment of polymorphonuclear (PMN) cells was calculated
      per 100 venules. Expression of E-selectin was determined by using
      immunohistochemical analysis. RESULT(S): E-selectin expression and
      polymorphonuclear-cell recruitment in the contralateral testis increased
      significantly after 1 hour of reperfusion and then remained unchanged during the
      first 24-48 hours, followed by a gradual decrease. Germ cell apoptosis in the
      contralateral testis increased after 6 hours of reperfusion, achieved statistical
      significance after 24 hours, and decreased after 72 hours of reperfusion.
      CONCLUSION(S): Germ cell apoptosis in the contralateral testis increases most
      significantly within the first 24-48 hours, followed by a gradual decrease, after
      IR injury. E-selectin expression and neutrophil recruitment increases within the
      first 6 hours and apparently may initiate the increase in germ cell apoptosis.

PMID- 18054002
TI  - Is painful rectovaginal endometriosis an intermediate stage of rectal
      endometriosis?
AB  - OBJECTIVE: To compare the history of pain complaints of women presenting
      rectovaginal and rectal endometriosis to show that rectovaginal locations may
      progress to a rectal involvement of the disease. DESIGN: Retrospective
      comparative study. SETTING: Department of Gynecology and Obstetrics, University
      Hospital Rouen, France. PATIENT(S): Thirty-two patients with rectovaginal
      endometriosis and 16 patients with rectal involvement. INTERVENTION(S):
      Standardized questionnaires recording the clinical history of painful deep
      endometriosis up to diagnosis. MAIN OUTCOME MEASURE(S): Length of time from onset
      of pain to diagnosis, types of pain, disability related to the pain, and number
      of physicians consulted before the diagnosis was made. RESULT(S): Women with
      rectal endometriosis had an earlier onset of dysmenorrhoea. The age of
      dysmenorrhoea and the length of time between the onset of the first pain to the
      first time that the endometriosis was suspected were significantly increased in
      women with rectal endometriosis. Pain during defecation was more frequent in
      patients with rectal endometriosis. Women consulted an average of three
      physicians before the endometriosis diagnosis was suggested. A nongynecologist
      physician made the diagnosis of rectovaginal and rectal endometriosis in
      respectively 26% and 31% of cases. CONCLUSION(S): Rectal endometriosis is
      associated with an earlier onset and a longer history of painful symptoms until
      the diagnosis was made when compared with rectovaginal endometriosis locations.
      These observations support the hypothesis that rectovaginal location may be an
      intermediate stage of rectal endometriosis.

PMID- 18054003
TI  - Oral contraceptive pill pretreatment in ovarian stimulation with GnRH antagonists
      for IVF: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the impact of oral contraceptive pill (OCP) pretreatment in
      ovarian stimulation for in vitro fertilization (IVF) using gonadotropin releasing
      hormone (GnRH) antagonists. DESIGN: Systematic review and meta-analysis of
      randomized controlled trials (RTC). SETTING: University IVF center. PATIENT(S):
      Infertile patients (n = 847), treated in four trials. INTERVENTION(S): Systematic
      literature search (MEDLINE, EMBASE, CENTRAL COCHRANE, conference proceedings,
      reference lists) for randomized trials on OCP treatment before stimulation with
      gonadotropins and GnRH antagonist for IVF. Meta-analysis of data yielding pooled
      odds ratios (OR) or weighted differences of the means (WMD) and 95% confidence
      intervals (CI). MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate per randomized
      woman. RESULT(S): Ongoing pregnancy rate per randomized woman was not found to be
      significantly different between patients with and those without OCP pretreatment
      (OR: 0.74, 95% CI: 0.53 to 1.03). Duration of gonadotropin stimulation (WMD:
      +1.41 days, 95% CI: +1.13 to +1.68) and gonadotropin consumption (WMD: +542 IU,
      95% CI: +127 to +956) were significantly increased after OCP pretreatment. No
      significant differences were observed regarding the number of cumulus-oocyte
      complexes (COCs) and the fertilization rates. CONCLUSION(S): A significant
      difference in ongoing pregnancy rates between patients who received OCP
      pretreatment and those who did not is currently not present, although further
      studies are necessary for more solid conclusions on pregnancy likelihood to be
      drawn.

PMID- 18054004
TI  - Infertility induced by cancer treatment: inappropriate or no information provided
      to majority of French survivors of cancer.
AB  - OBJECTIVE: To describe patients who reported treatment-induced infertility 2
      years after cancer diagnosis and to highlight what factors are related to the
      patients' lack of information on this topic before starting therapy. DESIGN:
      Cross-sectional study by telephone interview. SETTING: Representative French
      national sample of survivors 2 years after cancer diagnosis. PATIENT(S): 282
      women (<45 years) and 1137 men (<71 years). INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Self-reported treatment-induced infertility, and what information was
      provided on this issue before starting treatment, including information on
      systematic sperm cryopreservation. RESULT(S): Among the participants, 104 women
      (37%) and 346 men (30%) reported having treatment-induced infertility. Among
      them, 31 women (30%) and 45 men (13%) reported that they had not been informed
      about the risk of infertility before they started treatment. Logistic regressions
      showed that a lack of information was associated with older age and treatment
      without hormone therapy among women and older age, cancers other than prostate,
      and a lack of participation in treatment decision-making among men.
      CONCLUSION(S): Information about infertility risks and preservation methods
      should be provided more systematically to all treated patients, irrespective of
      their age.

PMID- 18054005
TI  - Successful pregnancy outcome after in vitro fertilization in a pancreas-kidney
      recipient.
AB  - OBJECTIVE: To describe the first case of IVF pregnancy in a pancreas-kidney
      recipient. DESIGN: Case report. SETTING: Reproductive Medicine Department,
      Hopital Edouard Herriot, Lyon, France. INTERVENTION(S): In vitro fertilization in
      a pancreas-kidney recipient. PATIENT(S): A 39 year-old nulliparous woman, with
      primary infertility and a history of pancreas-kidney transplant at 29 years of
      age. MAIN OUTCOME MEASURE(S): Multidisciplinary agreement for the couple to be
      managed by IVF. Follow-up of pregnancy and delivery. RESULT(S): Singleton IVF
      pregnancy in a pancreas-kidney recipient, maintained up to 34 weeks. Cesarian
      delivery ahead of labor. No severe maternal or fetal complications. Live birth.
      Normal postpartum renal function and glycemia. CONCLUSION(S): An IVF pregnancy is
      feasible in a pancreas-kidney recipient. Such treatment should follow agreement
      by all the medical teams following the patient. Pregnancy in a pancreas-kidney
      recipient is at-risk, requiring close monitoring.

PMID- 18054006
TI  - Kruppel-like factor 5 mediates cellular transformation during oncogenic KRAS
      induced intestinal tumorigenesis.
AB  - BACKGROUND & AIMS: Kruppel-like factor 5 (KLF5) is a zinc finger-transcription
      factor that regulates cell proliferation. Oncogenic KRAS mutations are commonly
      found in colorectal cancers. We aimed to determine whether KLF5 mediates KRAS
      functions during intestinal tumorigenesis. METHODS: The effects of KLF5 on
      proliferation and transformation were examined in IEC-6 intestinal epithelial
      cells stably transfected with inducible KRAS(V12G). KLF5 expression was examined
      in intestinal tumors derived from transgenic mice expressing KRAS(V12G) under
      villin promoter and in human colorectal cancers with mutated KRAS. RESULTS:
      Induction of KRAS(V12G) in IEC-6 cells resulted in increased expression of KLF5,
      accompanied by increased rates of proliferation and anchorage-independent growth.
      Inhibition of KLF5 expression by mitogen-activated protein kinase/extracellular
      signal-regulated kinase (MEK) inhibitors or KLF5-specific small interfering RNA
      reduced proliferation and anchorage-independent growth despite KRAS(V12G)
      induction. Human colorectal cancer cell lines with mutated KRAS contained high
      levels of KLF5 and reduction of KLF5 by MEK inhibitors or KLF5 small interfering
      RNA also led to reduced proliferation and transformation. In vivo, both
      intestinal tumors derived from mice transgenic for villin-KRAS(V12G) and human
      primary colorectal cancers with mutated KRAS contained high levels of KLF5 and
      increased staining of the proliferative marker Ki67. CONCLUSIONS: Elevated levels
      of KLF5 protein are strongly correlated with activating KRAS mutations in
      intestinal tumors in vitro and in vivo. Inhibition of KLF5 expression in tumor
      cells resulted in significantly reduced rates of proliferation and transforming
      activities. We conclude that KLF5 is an important mediator of oncogenic KRAS
      transforming functions during intestinal tumorigenesis.

PMID- 18054007
TI  - Roles of calcitonin gene-related peptide in maintenance of gastric mucosal
      integrity and in enhancement of ulcer healing and angiogenesis.
AB  - BACKGROUND & AIMS: The gastrointestinal tract is known to be rich in neural
      systems, among which afferent neurons are reported to exhibit protective actions.
      We tested whether an endogenous neuropeptide, calcitonin gene-related peptide
      (CGRP), can prevent gastric mucosal injury elicited by ethanol and enhance
      healing of acetic acid-induced ulcer using CGRP knockout mice (CGRP(-/-)).
      METHODS: The stomach was perfused with 1.6 mmol/L capsaicin or 1 mol/L NaCl, and
      gastric mucosal injury elicited by 50% ethanol was estimated. Levels of CGRP in
      the perfusate were determined by enzyme immunoassay. Gastric ulcers were induced
      by serosal application of absolute acetic acid. RESULTS: Capsaicin inhibited
      injured area dose-dependently. Fifty percent ethanol containing capsaicin
      immediately increased intragastric levels of CGRP in wild-type (WT) mice,
      although 50% ethanol alone did not. The protective action of capsaicin against
      ethanol was completely abolished in CGRP(-/-). Preperfusion with 1 mol/L NaCl
      increased CGRP release and reduced mucosal damage during ethanol perfusion.
      However, 1 mol/L NaCl was not effective in CGRP(-/-). Healing of ulcer elicited
      by acetic acid in CGRP(-/-) mice was markedly delayed, compared with that in WT.
      In WT, granulation tissues were formed at the base of ulcers, and substantial
      neovascularization was induced, whereas those were poor in CGRP(-/-). Expression
      of vascular endothelial growth factor was more markedly reduced in CGRP(-/-) than
      in WT. CONCLUSIONS: CGRP has a preventive action on gastric mucosal injury and a
      proangiogenic activity to enhance ulcer healing. These results indicate that the
      CGRP-dependent pathway is a good target for regulating gastric mucosal protection
      and maintaining gastric mucosal integrity.

PMID- 18054008
TI  - Disconnected pancreatic tail syndrome: potential for endoscopic therapy and
      results of long-term follow-up.
AB  - BACKGROUND: Limited published data exist that address the incidence and outcomes
      of patients with complete pancreatic-duct disruption. OBJECTIVE: Report on a
      single-center experience with this entity that emphasizes the feasibility of
      endoscopic therapy and long-term outcomes. DESIGN: Retrospective analysis.
      SETTING: Tertiary-care medical center (Portland, Maine). PATIENTS: A total of 189
      patients with pancreatic-fluid collections and/or pancreatic fistulas were
      retrospectively evaluated for the presence of a disconnected pancreatic tail.
      Patients meeting the definition of disconnected pancreatic tail syndrome (DPTS)
      with a minimum of 6 months' follow-up were analyzed. RESULTS: Thirty of 189
      patients (16%) met criteria for DPTS. Thirty-six drainage procedures were
      performed on 29 patients (mean 1.2 procedures per patient). In 22 of 29 patients
      (76%), the initial drainage procedure was successful. However, recurrent fluid
      collection(s) developed in 11 of 22 patients (50%) and was seen in those treated
      surgically and endoscopically. Disruption in the tail (n = 3) was uncommon but
      invariably required no surgical intervention. The median follow-up was 38 months
      (range 3-94 months). Diabetes mellitus developed in 16 of 30 patients (53%); 15
      of 30 patients (50%) had left-sided portal hypertension; 16 of 30 patients (53%)
      continue in active medical or surgical follow-up for recurrent symptoms
      attributable to the disconnected pancreatic tail. CONCLUSIONS: Of patients with a
      pancreatic-fluid collection and/or fistula, 16% will also have a disconnected
      pancreatic tail. Endoscopic and surgical drainage techniques are typically
      initially successful, but both suffer from a high rate of recurrence in the
      setting of DPTS. The majority of patients will require long-term follow-up
      because of complications and/or ongoing symptoms.

PMID- 18054009
TI  - Self-expandable metal stents in acute malignant colonic obstruction: shall you
      cross this bridge?

PMID- 18054010
TI  - Endoscopic submucosal dissection with internal traction for early gastric cancer
      (with video).
AB  - BACKGROUND: EMR techniques have high success rates for treating small lesions of
      the upper-GI tract; however, tumors larger than 15 mm are frequently removed by
      piecemeal resection, which is associated with an increased rate of disease
      recurrence and difficulty in histologically evaluating the specimen. OBJECTIVE:
      To describe a simple technique of using internal traction to facilitate
      endoscopic submucosal dissection (ESD) procedures in the excision of large, early
      gastric cancers. DESIGN: Case series. SETTING: A tertiary medical center in
      Taiwan. PATIENTS AND METHODS: Eight patients with early gastric cancers larger
      than 20 mm underwent ESD. INTERVENTIONS: A standard hemoclip modified with
      surgical suture was used to provide traction to improve visualization of the
      dissection plane during ESD. MAIN OUTCOME MEASUREMENTS: Proportion with complete
      en bloc resection. RESULTS: En bloc resection of the lesion was achieved in 8
      patients. One patient underwent additional surgery because an adequate safe
      margin was not obtained by ESD. LIMITATIONS: One endoscopist performed all
      procedures, and only 8 patients were studied in an uncontrolled manner.
      CONCLUSIONS: The internal traction method appears to facilitate en bloc ESD of
      early gastric cancers larger than 20 mm.

PMID- 18054012
TI  - Anterior versus posterior pin placement of pelvic C-clamp in relationship to
      anatomical structures: a cadaver study.
AB  - OBJECTIVES: The objective of this study was to compare anterior and posterior pin
      placement of the pelvic C-clamp with specific reference to the proximity of the
      sciatic nerve, sciatic notch, hip joint capsule, and superior gluteal
      neurovascular bundle. METHODS: The pelvic C-clamp (Synthes, Paoli, PA) was
      applied to eight extracted pelvic specimens and five full cadavers (26 hips in
      total). Anterior and posterior pin placements were measured in relationship to
      the described anatomical structures. RESULTS: In 100% of the hips the distance
      from the posterior pin to the hip joint capsule was in 21 (80.8%), 23 (88.5%),
      and 20 (76.9%) of the hips, the anterior pin distances were greater than the
      posterior pin distances to the sciatic nerve, sciatic notch, and superior gluteal
      neurovascular bundle, respectively. CONCLUSIONS: Anterior pin placement is
      further from all anatomical structures studies with the exception of the hip
      joint capsule. The posterior pin was closer to the sciatic nerve, sciatic notch,
      and superior gluteal neurovascular bundle in all cases. Clinical decision-making
      for C-clamp placement should be individualised on a case-by-case basis.

PMID- 18054011
TI  - Alpha-melanocyte-stimulating hormone mediates melanin-concentrating hormone
      induced anorexigenic action in goldfish.
AB  - In goldfish, intracerebroventricular (ICV) administration of melanin
      concentrating hormone (MCH) inhibits feeding behavior, and fasting decreases
      hypothalamic MCH-like immunoreactivity. However, while MCH acts as an
      anorexigenic factor in goldfish, in rodents MCH has an orexigenic effect.
      Therefore, we examined the involvement of two anorexigenic neuropeptides, alpha
      melanocyte-stimulating hormone (alpha-MSH) and corticotropin-releasing hormone
      (CRH), in the anorexigenic action of MCH in goldfish, using an alpha-MSH receptor
      antagonist, HS024, and a CRH receptor antagonist, alpha-helical CRH((9-41)). ICV
      injection of HS024, but not alpha-helical CRH((9-41)), suppressed MCH-induced
      anorexigenic action for a 60-min observation period. We then examined, using a
      real-time PCR method, whether MCH affects the levels of mRNAs encoding various
      orexigenic neuropeptides, including neuropeptide Y (NPY), orexin, ghrelin and
      Agouti-related peptide (AgRP), in the goldfish diencephalon. ICV administration
      of MCH at a dose sufficient to inhibit food consumption decreased the expression
      of mRNAs for NPY and ghrelin, but not for orexin and AgRP. These results indicate
      that the anorexigenic action of MCH in the goldfish brain is mediated by the
      alpha-MSH signaling pathway and is accompanied by inhibition of NPY and ghrelin
      synthesis.

PMID- 18054013
TI  - Transarterial embolisation for intractable post-traumatic oronasal haemorrhage
      following traumatic brain injury: evaluation of prognostic factors.
AB  - AIM: To analyse the outcomes of transarterial embolisation (TAE) for post
      traumatic oronasal haemorrhage following traumatic brain injury (TBI), for
      clinical application and prognosis. METHOD: Retrospective review of records of 17
      patients treated in the neurosurgical intensive care unit for TBI complicated
      with intractable post-traumatic oronasal haemorrhage requiring TAE. The Mann
      Whitney U-test, Wilcoxon signed rank test and Fisher's exact test were used in
      statistical analysis. RESULTS: TAE successfully stopped the post-traumatic
      oronasal haemorrhage in 13 of 17 cases. The internal maxillary artery was the
      most common haemorrhaging vessel requiring embolisation. Successful haemostasis
      contributed significantly to survival. CONCLUSION: Transarterial embolisation may
      stop intractable post-traumatic oronasal haemorrhage when conventional packing
      fails. Shock index (calculated as heart rate/systolic blood pressure) before and
      after TAE <1.2 and <0.8, respectively, and higher Glasgow Coma Scale (>8) before
      than after TAE, were positively correlated with survival.

PMID- 18054014
TI  - Profile of injuries arising from the 2005 Kashmir earthquake: the first 72 h.
AB  - BACKGROUND: The Kashmir Earthquake of October 8, 2005 had widespread destructive
      effects with in excess of 86,000 people killed and over 80,000 severely injured.
      Most hospitals were destroyed and limited facilities were available for medical
      service in the immediate aftermath. A small military hospital in Forward Kahuta,
      Pakistan, remained functional and was inundated with severely injured patients
      over 72h. METHODS: A retrospective review of medical records to document the
      injury patterns, subsequent treatment, infections and logistical requirements
      that occurred following this earthquake. RESULTS: One thousand five hundred and
      two patients were triaged over 72h. Four hundred and sixty eight (31.1%) patients
      required admission. Three hundred and nineteen (68.2%) patients were managed non
      operatively and 149 (31.8%) required a procedure under general anaesthesia. The
      most common type of injuries were: superficial lacerations (64.9%); fractures
      (22.2%); and soft tissue contusions/sprains (5.9%). There were 266 major injuries
      to the extremities (40.1% upper limb; 59.9% lower limb). Six patients had
      significant abdominal injuries, 66.6% of these required urgent laparotomy. 14.8%
      had clinically relevant infections at follow-up requiring surgical debridement or
      antibiotic therapy. CONCLUSIONS: Disaster response in the early phase of
      earthquake relief is complex, with local facilities often overwhelmed and
      damaged. Limb injuries are most likely; however facilities should have clear
      plans to deal with severe trauma including head injuries and penetrating
      abdominal trauma. Coordinated effort is required for success, with lessons learnt
      to improve future disaster management.

PMID- 18054015
TI  - Perineal hygiene in patients with pelvic fractures.
AB  - At the tertiary referral Orthopaedic Unit of St. Georges Hospital, it was noted
      that there was an unacceptably high number of soiled perinea in patients
      transferred from Base Hospitals. This not only exposed the patients to increased
      infection [Jepsen O. The effectiveness of preoperative skin preparations: an
      integrated review of the literature. AORN J 1993;58:477-82; and Nix D, Ermer
      Seltun J. A review of perineal skin care protocols and skin barrier product use.
      Ostomy Wound Manage 2004;50:59-67] but was also undignified and unacceptable for
      them. We decided to audit the problem with a view to finding out why this was
      happening and to improve the situation. A 2-year study was carried out over three
      distinct phases (phase 1: February-June 2004, phase 2: July-November 2004, phase
      3: February-November 2005). Observations of soiling were recorded in a
      questionnaire by the surgeon prior to surgery. Key system and clinical guidelines
      were implemented during the second phase, and the audit process was repeated. The
      percentage of clean perinea in phase 1 was 32%, phase 2 68% and phase 3 99.5%
      indicating a clear improvement in the overall system.

PMID- 18054016
TI  - Pancreatico-enterostomy for isolated main pancreatic duct disruption.
AB  - BACKGROUND: We present our experiences with isolated main pancreatic duct
      injuries due to blunt trauma, managed by pancreatico-enterostomies. METHODS: This
      is a retrospective study of seven patients, one female and six males who
      presented between 1997 and 2005, whose ages ranged from 10 to 54 years. Three
      were due to motor vehicle accidents, two due to blunt assault, one pedestrian
      vehicle accident and one go-cart accident. Four presented acutely and were
      managed surgically within 24h; two were delayed by 3 days and one by 14 days. Six
      had pre-operative CT scans; one had an ERCP confirming ductal transection by
      contrast extravasation. RESULTS: Five pancreatico-gastrostomies and two
      pancreatico-jejenostomies were performed. Three patients complicated; one by
      biliary cutaneous fistula after a left hepatic segmentectomy, one with an amylase
      rich low output fistula and one with haematemesis, for which no cause could be
      identified. All complications were managed conservatively. Post-operative follow
      up ranged between 4 and 20 weeks. No deaths occurred. CONCLUSION: In a stable
      patient, pancreatico-enterostomy for an isolated main pancreatic duct injury
      appears to be a viable option and simpler to perform than distal pancreatectomy
      with splenic preservation. Furthermore, it has the advantage of pancreatic tissue
      and spleen preservation and a low fistula rate. The authors believe pancreatico
      gastrostomy to be the easier to perform.

PMID- 18054017
TI  - An update on the management of high-energy pilon fractures.
AB  - High energy pilon fractures present a unique challenge to the patient and
      orthopaedic surgeon. Care for the soft tissue envelope is as important as
      management of this articular fracture. This article reviews the fundamental
      principles for treatment of the patient with severe pilon fracture. Staged
      operative care is emphasised to prevent wound and infectious complications which
      have historically plagued pilon fracture surgery. New innovations directed at
      improving results are discussed including biological planting and wound care
      using the vacuum assisted closure device. Lastly, validated outcomes are
      presented which highlight the severity of these injuries despite optimal care.

PMID- 18054018
TI  - Should the galvanic combination of titanium and stainless steel surgical implants
      be avoided?
AB  - It is recommended that one should not combine different metals in orthopaedic
      devices. The least noble metal in such a galvanic coupling is more likely to
      corrode. However, some studies have failed to show increased corrosion when
      titanium and stainless steel are combined. The aim of this study was to determine
      the fretting corrosion of the contact areas between screws and plates made of
      these dissimilar metals used for internal fixation of bone fractures. The plates
      were fixed to a bone-simulating material and subjected to tensile and compressive
      forces in both human serum and Hank's solution. The outcome variables included in
      the analyses were weight loss, and release of Ti, Cr, Ni and Mo to the different
      media. Results from the multiple combinations were subjected to multivariate
      statistics. Principal component analysis visualised our findings and allowed
      classification of similar samples and separation of discrepant groups of samples.
      We found a significant effect of the test medium, but no dramatic effect due to
      mixing of metals. The titanium screws and plates corroded more in serum than in
      saline, while the opposite was true for stainless steel. Combination of
      dissimilar screws and plates did not cause higher weight loss or metal release
      than the single-material constructions, indicating comparable clinical safety.

PMID- 18054019
TI  - Perioperative hemodilutional autologous blood transfusion in burn surgery.
AB  - It is important to avoid or minimise allogeneic blood transfusion, because of
      possible alloimmunisation or disease transmission. In burn cases these risks are
      high, and predonated autologous transfusion is not practical. Perioperative
      haemodilutional autologous blood transfusion is considered applicable in burn
      surgery. This study evaluates the effectiveness of the technique in the treatment
      of burns.

PMID- 18054020
TI  - Road traffic collisions in Bursa, Turkey, during 2003, 2004 and 2005.
AB  - AIM: To highlight the demographic pattern of road traffic injuries in Bursa and
      to improve emergency care and health facility-based treatment. METHODS: Records
      of all registered road traffic collisions maintained by the Uludag University
      Emergency Department in Bursa for the period 2003 to 2005 and trauma files of
      1307 road traffic collision victims were examined in this study. A form was
      designed to document patients' age, gender, type of trauma, time of trauma (hour,
      day, month and year), type and time to hospital of transport, presence of safety
      devices, presence of alcohol and blood alcohol concentration, localisations of
      wounds, trauma scores and outcomes. RESULTS: Of the 1307 cases, 418 (32%) were
      female and 889 (68%) were male. Ages ranged from 3 months to 87 years; mean age
      (+/-S.D.) was 34.8 (+/-17.3) years. The mean (+/-S.D.) ages of women and men were
      35+/-17.6 and 34.7+/-17.2 years, respectively. Trauma was most commonly sustained
      within the motor vehicle (72.2%), followed by pedestrian injuries (21.7%),
      motorcycle injuries (5.5%) and bicycle injuries (0.6%). Collisions were most
      frequent in summer (34.7%) and on Fridays and weekends (48.5%). Seat belts were
      used in only 1.8% of incidents. In 90 cases (6.9%) alcohol was found in the
      blood; mean blood alcohol concentration was 139.2+/-88.3mg/dl. CONCLUSIONS: The
      identification of RTC characteristics may contribute to the development of injury
      prevention measures. Road travel requires extra attentiveness at peak accident
      times. Seat-belt use should increase, as well as use of other safety equipment
      such as collision helmets. Shorter transportation time of casualties to hospital
      would improve outcome.

PMID- 18054021
TI  - Quantification and characterisation of endothelial injury after trauma.
AB  - The microenvironment theory has become very popular for providing mechanisms
      which explain the development of often lethal posttraumatic complications such as
      systemic inflammatory response syndrome (SIRS), adult respiratory distress
      syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). With the recent
      advances in molecular biology and the ever-expanding understanding of trauma
      pathophysiology, immunomonitoring in trauma patients attempts to characterise and
      quantify novel molecules in order to predict patients at risk. This review
      article assesses the existing evidence on the biomarkers of endothelial injury
      and their potential utility as quantification parameters of endothelial
      dysfunction in trauma patients.

PMID- 18054022
TI  - Chitotriosidase and YKL-40 in normal and pre-eclamptic pregnancies.
AB  - OBJECTIVE: To compare macrophage activation in normal and pre-eclamptic
      pregnancies by determining YKL-40 concentration and chitotriosidase activity in
      maternal and cord serum. METHODS: In this prospective case-control study samples
      of maternal peripheral blood and umbilical venous blood were collected from 28
      pre-eclamptic and 24 normotensive pregnant women and their newborns. YKL-40
      concentration and chitotriosidase activity were determined by enzyme-linked
      immunoassay and fluorometry, respectively. RESULTS: Chitotriosidase activity in
      maternal and cord serum and YKL-40 concentration in cord serum were significantly
      higher in pre-eclamptic pregnancies (P<0.001), but there was no significant
      difference in maternal serum levels of YKL-40 between the case and control groups
      (P>0.05). There was a significant positive correlation between diastolic blood
      pressure and (1) chitotriosidase activity in both maternal and cord serum and (2)
      cord serum concentration of YKL-40 (r=0.61, r=0.84, and r=0.58, respectively).
      CONCLUSION: This study may be the first to demonstrate maternal and fetal
      macrophage activation in pre-eclampsia.

PMID- 18054023
TI  - An international matched cohort study of the contribution of metabolic
      impairments to subclinical atherosclerosis in United Kingdom and Jamaican African
      Caribbeans.
AB  - BACKGROUND: A gradient of increased vascular risk exists across the African
      diaspora. We hypothesised that increased insulin resistance with environmental
      transition contributes to this risk. METHODS: The study was undertaken in 73
      healthy African-Caribbeans in the UK and 151 age and sex matched African
      Caribbeans in Jamaica. Body mass index (BMI), fasting insulin, insulin
      resistance, carotid intima media thickness (CIMT) and endothelium dependent
      vasodilatation (EDV) were compared. CIMT was measured ultrasonographically in the
      distal 1cm of both common carotid arteries. EDV was measured the absolute change
      from baseline in the Reflection index (RI) of the digital volume pulse during
      intravenous infusion of albuterol (DeltaRI(ALB)). RESULTS: UK African-Caribbeans
      had greater CIMT (mean difference 0.124 [95% C.I. 0.075-0.173] mm, p<0.0001) and
      decreased EDV (mean difference in DeltaRI(ALB) 5.1 [95% C.I. 2.5-7.6] percentage
      points, p<0.0001). This was associated with higher insulin concentrations (mean
      difference 1.6 [95% C.I. 1.3-4.1] microU/mL, p=0.038) and greater HOMA score (2.8
      versus 2.0; p=0.035) despite no significant differences in BMI (28.8 versus 27.6;
      p=0.168) or the waist to hip ratio (0.86 versus 0.85; p=0.188). HOMA scores
      correlated positively with CIMT (r=0.35, p=0.01) and negatively with DeltaRI(ALB)
      (r=-0.17; p=0.02) in UK, but not in Jamaican, African-Caribbeans. A significant
      interaction was seen between HOMA and UK domicile for CIMT (p<0.0001) and between
      fasting insulin and UK domicile for DeltaRI(ALB) (p<0.0001). CONCLUSIONS:
      Increased insulin resistance, associated with living in a nutritionally enriched
      environment, may contribute to early subclinical atherosclerosis in UK African
      Caribbeans.

PMID- 18054024
TI  - Strains and stresses in sub-dermal tissues of the buttocks are greater in
      paraplegics than in healthy during sitting.
AB  - A pressure-related deep tissue injury (DTI) is a severe pressure ulcer, which
      initiates in muscle tissue overlying a bony prominence (e.g. the ischial
      tuberosities, IT) and progresses outwards through fat and skin, unnoticed by the
      paralyzed patient. We recently showed that internal strains and stresses in
      muscle and fat of individuals at anatomical sites susceptible to DTI can be
      evaluated by integrating Open-MRI scans with subject-specific finite element (FE)
      analyzes (Linder-Ganz et al., Journal of Biomechanics, 2007); however, sub-dermal
      soft tissue strains/stresses from paraplegics are still missing in literature. We
      hypothesize that the pathoanatomy of the buttocks in paraplegia increases the
      internal soft tissue loads under the IT, making these patients inherently
      susceptible to DTI. We hence compared the strain and stress peaks in the gluteus
      muscle and fat tissues under the IT of six healthy and six paraplegic patients,
      using the coupled MRI-FE method. Peak principal compression, principal tension,
      von Mises and shear strains in the gluteus were 1.2-, 3.1-, 1.4- and 1.4-fold
      higher in paraplegics than in healthy, respectively (p<0.02). Likewise, peak
      principal compression, principal tension, von Mises and shear stresses in the
      gluteus were 1.9-, 2.5-, 2.1- and 1.7-fold higher for the paraplegics (p<0.05).
      Peak gluteal compression and shear stresses decreased by as much as 70% when the
      paraplegic patients moved from a sitting to a lying posture, indicating on the
      effectiveness of recommending such patients to lie down after prolonged periods
      of sitting. This is the first attempt to compare internal soft tissue loads
      between paraplegic and healthy subjects, using an objective standardized
      bioengineering method of analysis. The findings support our hypothesis that
      internal tissue loads are significantly higher in paraplegics, and that postural
      changes significantly affect these loads. The method of analysis is useful for
      quantifying the effectiveness of various interventions to alleviate sub-dermal
      tissue loads at sites susceptible to pressure ulcers and DTI, including cushions,
      mattresses, recommendations for posture and postural changes, etc.

PMID- 18054025
TI  - Temporal characteristics of plantar shear distribution: relevance to diabetic
      patients.
AB  - Diabetic foot ulcers are known to have a biomechanical etiology. Among the
      mechanical factors that cause foot lesions, shear stresses have been either
      neglected or underestimated. The purpose of this study was to determine various
      plantar pressure and shear variables in the diabetic and control groups and
      compare them. Fifteen diabetic patients with neuropathy and 20 non-diabetic
      subjects without foot symptoms were recruited. Subjects walked on a custom-built
      platform capable of measuring local normal and tangential forces simultaneously.
      Pressure-time integral quantities were increased by 54% (p=0.013) in the diabetic
      group. Peak AP and resultant shear magnitudes were found to be about 32% larger
      (p<0.05), even though diabetic subjects walked at a slower velocity. Lower AP and
      ML stress range (peak-to-peak) values were observed in the control subjects
      (p<0.05). Shear-time integral values were increased in the diabetic group by 61%
      and 132% for AP and resultant shear cases, respectively (p<0.05). Plantar shear
      is known to be a factor in callus formation and has previously been associated
      with higher ulcer incidence. During gait, shear stresses are induced with twice
      the frequency of pressure characteristically. Therefore, plantar shear should be
      investigated further from a broader perspective including the temporal
      specifications and fatigue failure characteristics of the affected plantar
      tissue.

PMID- 18054026
TI  - Contributions of capillary electrophoresis to neuroscience.
AB  - Capillary electrophoresis (CE) is a small-volume separation approach amenable to
      the analysis of complex samples for their small molecule, peptide and protein
      content. A number of the features of CE make it a method of choice for addressing
      questions related to neurochemistry. The figures of merit inherent to CE that
      make it well suited for studying cell-to-cell and intracellular signaling include
      small sample volumes, high separation efficiency, the ability for online analyte
      concentration, and compatibility with sensitive and high-information content
      detection methods. A variety of instrumental aspects are detailed, including
      detection methods and sampling techniques that are particularly useful for the
      analysis of signaling molecules. Studies that have used these techniques to
      increase our understanding of neurobiology are emphasized throughout. One notable
      application is single neuron chemical analysis, a research area that has been
      greatly advanced by CE.

PMID- 18054027
TI  - Preparation of novel beta-cyclodextrin chiral stationary phase based on click
      chemistry.
AB  - A facile strategy based on click chemistry for preparation of the structurally
      well-defined native beta-cyclodextrin (beta-CD) based chiral stationary phase
      (CSP) was proposed. The beta-CD CSP was evaluated by enatioseparation of benzoin,
      trans-stilbene oxide, Troger's base, bendroflumethiazide, ketoprofen,
      chlorthalidone, three flavanone compounds and two beta-adrenergic blocking agents
      under reversed phase high performance liquid chromatography. The chromatographic
      results demonstrate the chiral separation ability of click beta-CD CSP and
      illustrate the usefulness of click chemistry in the preparation of beta-CD based
      CSP.

PMID- 18054028
TI  - Comprehensive two-dimensional liquid chromatography applying two parallel columns
      in the second dimension.
AB  - The design of a new interface for comprehensive two-dimensional liquid
      chromatography (LC x LC) is described. To the conventionally used LC x LC system
      with the loop-type interface consisting of a two-position/ten-port switching
      valve equipped with two loops, an extra two-position/ten-port switching valve, a
      detector, a pump and a second column placed in parallel with the column in the
      second dimension, are added. The features of the interface are that the
      separation space in the second dimension is significantly enlarged and that the
      number of fractions transferred from the first to the second dimension can be
      increased, reducing the risk to lose resolution of the primary dimension. The
      potential of the system in NPLC x 2RPLC is illustrated with the analysis of a
      standard mixture and a lemon oil extract. For the lemon oil analysis, the
      effective peak capacity was increased from 437 using a conventional interface to
      1095 with the new interface. RPLC x 2RPLC in combination with reduced modulation
      times was applied to the analysis of steroids and to the detection of impurities
      at the 0.05% relative concentration level in a sulfonamide drug sample.

PMID- 18054029
TI  - Development of new-type rapid analysis technology of polychlorinated biphenyls by
      using liquid chromatographic clean-up material (polyvinyl alcohol gel).
AB  - We developed a new-type rapid polychlorinated biphenyl (PCB) analysis technology
      on the basis of a liquid chromatographic clean-up system combined with a large
      volume injection GC-LRMS. Among 18 kinds of materials such as polymer gels,
      normal-phase silica gels, reversed-phase silica gels, carbon material and ion
      exchange material, polyvinyl alcohol (PVA) gel and poly (hydroxylmethacrylate)
      gel were found to give rather good separation performance for insulating oil.
      Especially, PVA gel was confirmed to be the most suitable for rapid PCB analysis
      because of its least required quantity of fraction liquid as well as the highest
      resolution. Then, we confirmed elution characteristics of all PCB isomers and
      removal efficiency of insulating oil on PVA gel under an optimized condition, and
      established high-performance clean-up system using a combination of octadecyl
      silica gel (ODS), porous graphite carbon (PGC) and PVA gel. In this system, we
      applied newly valve-switching method that could remove other impurities. In
      addition, it was demonstrated that the proposed clean-up system could become
      highly sensitive and rapid PCB analysis technology with 2-h analysis time, lower
      measurement limit of less than 0.05 mg/kg, and a variation coefficient of less
      than 5%, by coupling with a large-volume injection type GC-LRMS. Thus, we can
      conclude that this rapid PCB analysis technology has not only good correlativity
      (R2>0.999) with standard analysis method but also high durability and can be
      fully applied to actual PCB-treatment plants.

PMID- 18054030
TI  - Separation of 7-xylosyl-10-deacetyl paclitaxel and 10-deacetylbaccatin III from
      the remainder extracts free of paclitaxel using macroporous resins.
AB  - The separation and enrichment of 10-deacetylbaccatin III (10-DAB III) and 7
      xylosyl-10-deacetyl paclitaxel were studied on seven macroporous resins with
      special structures. The performance of 7-xylosyl-10-deacetyl paclitaxel and 10
      DAB III on macroporous resins including AB-8, ADS-17, ADS-21, ADS-31, ADS-8,
      H1020 and NKA-II was compared according to their adsorption and desorption
      properties. AB-8 provided a much higher adsorption capacity for 7-xylosyl-10
      deacetyl paclitaxel and 10-DAB III than other resins, and its adsorption data
      fitted well to the Langmuir and Freundlich isotherm. According to the adsorption
      and desorption capacities and the adsorption isotherms, AB-8 demonstrated a
      remarkable capability for the preparative separation of 7-xylosyl-10-deacetyl
      paclitaxel and 10-DAB III from the remainder extracts free of paclitaxel. In
      order to optimize parameters of separation, dynamic adsorption and desorption
      experiments were carried out on the columns packed with AB-8 resin. The optimal
      conditions were: the processing volume 15 BV; concentrations of 7-xylosyl-10
      deacetyl paclitaxel and 10-DAB III in feed solution 0.0657 mg/mL and 0.1494
      mg/mL; flow rate 1 mL/min; temperature 35 degrees C. The gradient elution program
      was as follows: 30% ethanol for 3 BV, then 80% of ethanol for 6 BV, flow rate 1
      mL/min. After the AB-8 resin treatment, the contents of 7-xylosyl-10-deacetyl
      paclitaxel and 10-DAB III in the product had increased from 0.053% and 0.2% to
      3.34% and 1.69%, which were 62.43-fold and 8.54-fold of those in the untreated
      extracts, respectively, and the recoveries of 7-xylosyl-10-deacetyl paclitaxel
      and 10-DAB III were 85.85% and 52.78%. The performance achieved good separation
      and higher recovery of 7-xylosyl-10-deacetyl paclitaxel and 10-DAB III from
      remainder extracts free of paclitaxel by using AB-8 resin. It is a fast and
      effective method for the separation and enrichment of 7-xylosyl-10-deacetyl
      paclitaxel and 10-DAB III.

PMID- 18054031
TI  - Influence of n-alkyl acids on the percolative phenomena in AOT-based
      microemulsions.
AB  - A study was carried out on the influence of the n-alkyl acid addition on the
      electric percolation of AOT/iso-octane/water microemulsions ([AOT] = 0.5 M and W=
      [H(2)O]/[AOT] = 22.2). The observed influence has been explained taking into
      account the organic nature of these molecules and, hence, their capacity of
      disturbing the structure of the AOT-film. For these reasons, relationships with
      their molecular structure (chain length) were analysed.

PMID- 18054032
TI  - Modulation of the adsorption properties at air-water interfaces of complexes of
      egg white ovalbumin with pectin by the dielectric constant.
AB  - The possibility of modulating the mesoscopic properties of food colloidal systems
      by the dielectric constant is studied by determining the impact of small amounts
      of ethanol (10%) on the adsorption of egg white ovalbumin onto the air-water
      interface in the absence and presence of pectin. The adsorption kinetics was
      monitored using tensiometry. The addition of ethanol resulted in considerably
      slower adsorption of the protein onto the interface, and this effect was enhanced
      when the protein was in complex with the pectin. Time-resolved fluorescence
      measurements demonstrated that in the case of noncomplexed ovalbumin the addition
      of ethanol resulted in a more condensed protein surface layer where ovalbumin
      adopted a preferred orientation at the interface. In contrast, the effect of
      ethanol on the ovalbumin-pectin complex suggested a pronounced multipoint
      electrostatic interaction between protein and polyelectrolyte and the formation
      of a more rigid spatial arrangement within the complex, thereby leading to
      suppressed protein-protein interactions. From this work it is concluded that by
      the enhanced binding affinity between ovalbumin and pectin a strong effect on the
      adsorption properties of the protein can be accomplished. This work does
      therefore illustrate how solvent quality can be exploited effectively to enhance
      or suppress protein functional behavior in complex applications containing air
      water interfaces.

PMID- 18054033
TI  - Viscous solvent colloidal system for direct visualization of suspension
      structure, dynamics and rheology.
AB  - We introduce a model colloid system comprised of particles dispersed in a viscous
      solvent that can be applied to 3D direct visualization studies of suspension
      structure, dynamics and rheology. The colloids are poly(methyl methacrylate)
      (PMMA) spheres sterically stabilized by a copolymer of poly(diphenyl-dimethyl)
      (DPDM) siloxane that matches the refractive index of PMMA. The monodisperse
      particles, synthesized with mean diameter varying from 0.7 to 1.1 microm, are
      stably dispersed in a DPDM siloxane solvent, with viscosity varying from 2.2 to
      4.3 Pa s at 20 degrees C. As opposed to other classes of PMMA colloids dispersed
      in organic solvents, this system displays minimal charge interactions. At room
      temperature, pair potential interactions (measured by extrapolation of pair
      correlation functions to infinite dilution) are well modeled by a generalized
      Lennard-Jones alpha-2alpha potential (alpha=10) with dimensionless interaction
      energy, epsilon/k(B)T=0.6. We use the DPDM-PMMA colloidal system in conjunction
      with confocal microscopy studies to measure: (i) the radial distribution function
      in 3D at dilute concentrations and (ii) the colloid self-diffusivity in 3D at
      dilute concentrations. Both measurements, neither previously reported in
      uncharged systems, are facilitated by the slow, viscous dynamics of the system.
      We also show that the viscosity and particle size of the system are such that the
      high-volume fraction shear thickening transition can be accessed at shear rates
      amenable to direct visualization.

PMID- 18054034
TI  - Bounds for local and average microwave absorption in heterogeneous systems.
AB  - A simple expression for the local energy loss rate in binary mixtures is derived
      that can be used to analyze measured dielectric spectra, to check their validity
      or to control whether the specified material composition is consistent. Together
      with well-known permittivity bounds it is applied to analyze recently published
      data on microwave absorption of emulsions containing aqueous micro- and nano
      droplets. It follows that these data are inconsistent and violate energy
      conservation.

PMID- 18054035
TI  - Tuning aggregation of microemulsion droplets and silica nanoparticles using
      solvent mixtures.
AB  - The effect of solvent on stability of water-in-oil microemulsions has been
      studied with AOT (sodium bis(2-ethylhexyl)sulfosuccinate) and different solvent
      mixtures of n-heptane, toluene and dodecane. Dynamic light scattering DLS was
      used to monitor the apparent diffusion coefficient D(A) and effective
      microemulsion droplet diameter on changing composition of the solvent.
      Interdroplet attractive interactions, as indicated by variations in D(A), can be
      tuned by formulation of appropriate solvent mixtures using heptane, toluene, and
      dodecane. In extreme cases, solvent mixtures can be used to induce phase
      transitions in the microemulsions. Aggregation and stability of model AOT
      stabilized silica nanoparticles in different solvents were also investigated to
      explore further these solvent effects. For both systems the state of aggregation
      can be correlated with the effective molecular volume of the solvent V(mol)(eff)
      mixture.

PMID- 18054036
TI  - The emergence of motor imagery in children.
AB  - A total of 80 children (40 5-year-olds and 40 7-year-olds) took part in an
      experiment to evaluate their capacity to mentally evoke a motor image of their
      own displacement. Using a chronometry paradigm, movement duration was compared in
      a task where children were asked to move in order to take a puppet back to its
      home (actual) and to think about themselves executing the same action (virtual).
      Movement durations for actual and virtual displacements were obtained in two
      conditions, where either no information was provided about the weight of the
      puppet to be displaced (standard situation) or the puppet was described as being
      heavy (informed situation). A significant correlation between actual and virtual
      walking durations was observed for 7-year-olds in the informed condition. This
      result provides evidence for a motor imagery process emerging in 7-year-olds when
      children are required to think about themselves in action.

PMID- 18054037
TI  - In vitro study of the antimicrobial activity of Brazilian propolis against
      Paenibacillus larvae.
AB  - The honey bee disease American foulbrood (AFB) is a serious problem since its
      causative agent (Paenibacillus larvae) has become increasingly resistant to
      conventional antibiotics. The objective of this study was to investigate the in
      vitro activity of propolis collected from various states of Brazil against P.
      larvae. Propolis is derived from plant resins collected by honey bees (Apis
      mellifera) and is globally known for its antimicrobial properties and
      particularly valued in tropical regions. Tests on the activity of propolis
      against P. larvae were conducted both in Brazil and Minnesota, USA using two
      resistance assay methods that measured zones of growth inhibition due to
      treatment exposure. The propolis extracts from the various states of Brazil
      showed significant inhibition of P. larvae. Clear dose responses were found for
      individual propolis extracts, particularly between the concentrations of 1.7 and
      0.12 mg propolis/treatment disk, but the source of the propolis, rather than the
      concentration, may be more influential in determining overall activity. Two of
      the three tested antibiotics (tylosin and terramycin) exhibited a greater level
      of inhibition compared to most of the Brazilian samples, which could be due to
      the low concentrations of active compounds present in the propolis extracts.
      Additionally, the majority of the Brazilian propolis samples were more effective
      than the few collected in MN, USA. Due to the evolution of resistance of P.
      larvae to conventional antibiotic treatments, this research is an important first
      step in identifying possible new active compounds to treat AFB in honey bee
      colonies.

PMID- 18054038
TI  - Regulation of Akt/PKB activity by P21-activated kinase in cardiomyocytes.
AB  - Akt/PKB is a critical regulator of cardiac function and morphology, and its
      activity is governed by dual phosphorylation at active loop (Thr308) by
      phosphoinositide-dependent protein kinase-1 (PDK1) and at carboxyl-terminal
      hydrophobic motif (Ser473) by a putative PDK2. P21-activated kinase-1 (Pak1) is a
      serine/threonine protein kinase implicated in the regulation of cardiac
      hypertrophy and contractility and was shown previously to activate Akt through an
      undefined mechanism. Here we report Pak1 as a potential PDK2 that is essential
      for Akt activity in cardiomyocytes. Both Pak1 and Akt can be activated by
      multiple hypertrophic stimuli or growth factors in a phosphatidylinositol-3
      kinase (PI3K)-dependent manner. Pak1 overexpression induces Akt phosphorylation
      at both Ser473 and Thr308 in cardiomyocytes. Conversely, silencing or
      inactivating Pak1 gene diminishes Akt phosphorylation in vitro and in vivo.
      Purified Pak1 can directly phosphorylate Akt only at Ser473, suggesting that Pak1
      may be a relevant PDK2 responsible for AKT Ser473 phosphorylation in
      cardiomyocytes. In addition, Pak1 protects cardiomyocytes from cell death, which
      is blocked by Akt inhibition. Our results connect two important regulators of
      cellular physiological functions and provide a potential mechanism for Pak1
      signaling in cardiomyocytes.

PMID- 18054039
TI  - The role of the unfolded protein response in the heart.
AB  - The misfolding of nascent proteins, or the unfolding of proteins after synthesis
      is complete, can occur in response to numerous environmental stresses, or as a
      result of mutations that de-stabilize protein structure. Cells have developed
      elaborate protein quality control systems that recognize improperly folded
      proteins and either refold them or facilitate their degradation. One such quality
      control system is the unfolded protein response, or the UPR. The UPR is a highly
      conserved signal transduction system that is activated when cells are subjected
      to conditions that alter the endoplasmic reticulum (ER) in ways that impair the
      folding of nascent proteins in this organelle. Recent observations indicate that
      in the heart, the UPR is activated during acute stresses, including
      ischemia/reperfusion, as well as upon longer term stresses that lead to cardiac
      hypertrophy and heart failure. Moreover, certain aspects of the UPR are activated
      during, and are required for proper heart development. This review summarizes
      recent studies of the UPR in the heart, focusing on the possible roles of the UPR
      in contributing to, or protecting from ischemia/reperfusion damage.

PMID- 18054040
TI  - Globular adiponectin but not full-length adiponectin induces increased
      procoagulability in human endothelial cells.
AB  - Adiponectin (APN), a recently discovered adipocytokine, is present in human serum
      in a full length (fAPN) and a globular form (gAPN). gAPN is a proteolytic
      cleavage product of fAPN and seems to show independent biological activities
      compared to the properties of fAPN. The influence of gAPN and fAPN on
      procoagulability of cells is still unknown. This study examined the effect of
      gAPN and fAPN on the expression of tissue factor (TF), the initiator of the
      extrinsic coagulation system, in human umbilical vein endothelial cells (HUVECs).
      TF activity was measured by a chromogenic assay, TF mRNA by real-time PCR and TF
      protein by western blot. We found TF activity to be increased after activation by
      gAPN (3 microg/mL) compared to a non-stimulated control (169.0+/-19.23 U versus
      501.9+/-38.95 U, p<0.001). Furthermore, TF mRNA and TF protein was increased dose
      dependently after gAPN stimulation. The gAPN-induced rise of TF activity and TF
      mRNA was significantly reduced by inhibition of the MAP kinases ERK1/2, p38 and
      JNK. Contrary to gAPN, stimulation with fAPN did not lead to these procoagulant
      effects. In conclusion, gAPN increased TF transcription, expression and activity
      in HUVECs. Therefore, our data support the theory that gAPN but not fAPN supports
      the cellular procoagulability via TF upregulation.

PMID- 18054041
TI  - Expression profiling of cardiac genes in Tako-Tsubo cardiomyopathy: insight into
      a new cardiac entity.
AB  - Tako-Tsubo cardiomyopathy (TTC) is characterized by a transient contractile
      dysfunction, but its specific pathomechanism remains unknown. Thus, we performed
      a systematic expression profiling of genes by microarray analysis in the acute
      phase and after functional recovery. We studied 3 female patients presenting with
      TTC. Complementary RNA was isolated from left ventricular biopsies taken in the
      acute phase (group A) and after functional recovery (group B). It was profiled
      for gene expression using cDNA microarrays. Functionally related genes were
      determined with the Gene Set Enrichment Analysis (GSEA) bioinformatic tool.
      Validation of selected genes was performed by means of real-time PCR and
      immunohistochemistry. In group A, different functional gene sets, such as Nrf2
      induced genes, triggered by oxidative stress, and protein biosynthesis were
      significantly overrepresented among the upregulated targets. Increased
      transcription of GPX1, CAT, RPS6, and eIF4E was confirmed by RT-PCR. The targets
      of the Akt/PKB signaling showed significant upregulation in both groups.
      Immunohistochemistry showed that the downstream targets NF-kappaB and BcL-X(L)
      are upregulated and activated. Gene sets involved in energy metabolism (oxidative
      phosphorylation, mitochondrial genes) showed no differences in group A but were
      overexpressed in group B. This study demonstrated a significant contribution of
      oxidative stress to the pathomechanism of TTC; it is possibly triggered by excess
      catecholamine. Increased protein biosynthesis and an activated cell survival
      cascade can be interpreted as potential compensatory mechanisms. After functional
      recovery, processes involved in energy metabolism play a pivotal role, thereby
      potentially contributing to the normalization of contractile function.

PMID- 18054042
TI  - Two structures of a lambda Cro variant highlight dimer flexibility but disfavor
      major dimer distortions upon specific binding of cognate DNA.
AB  - Previously reported crystal structures of free and DNA-bound dimers of lambda Cro
      differ strongly (about 4 A backbone rmsd), suggesting both flexibility of the
      dimer interface and induced-fit protein structure changes caused by sequence
      specific DNA binding. Here, we present two crystal structures, in space groups
      P3(2)21 and C2 at 1.35 and 1.40 A resolution, respectively, of a variant of
      lambda Cro with three mutations in its recognition helix (Q27P/A29S/K32Q, or PSQ
      for short). One dimer structure (P3(2)21; PSQ form 1) resembles the DNA-bound
      wild-type Cro dimer (1.0 A backbone rmsd), while the other (C2; PSQ form 2)
      resembles neither unbound (3.6 A) nor bound (2.4 A) wild-type Cro. Both PSQ form
      2 and unbound wild-type dimer crystals have a similar interdimer beta-sheet
      interaction between the beta1 strands at the edges of the dimer. In the former,
      an infinite, open beta-structure along one crystal axis results, while in the
      latter, a closed tetrameric barrel is formed. Neither the DNA-bound wild-type
      structure nor PSQ form 1 contains these interdimer interactions. We propose that
      beta-sheet superstructures resulting from crystal contact interactions distort
      Cro dimers from their preferred solution conformation, which actually resembles
      the DNA-bound structure. These results highlight the remarkable flexibility of
      lambda Cro but also suggest that sequence-specific DNA binding may not induce
      large changes in the protein structure.

PMID- 18054043
TI  - Partially folded bovine pancreatic trypsin inhibitor analogues attain fully
      native structures when co-crystallized with S195A rat trypsin.
AB  - Crystal structures, at 1.7 A resolution, were solved for complexes between each
      of two chemically synthesized partially folded analogues of bovine pancreatic
      trypsin inhibitor (BPTI) with the proteolytically inactive rat trypsin mutant
      S195A. The BPTI analogue termed [14-38](Abu) retains only the disulfide bond
      between Cys14 and Cys38, while Cys5, Cys30, Cys51, and Cys55 are replaced by
      isosteric alpha-amino-n-butyric acid residues. The analogue K26P,A27D[14-38](Abu)
      contains two further replacements, by statistically favored residues, in the type
      I beta-turn that has been suggested to be a main site for initiation of BPTI
      folding. As a control, the structure of the complex between S195A trypsin and
      wild-type BPTI was also solved. Despite significant differences in the degree of
      structure detected among these three BPTIs in solution by several biophysical
      techniques, their tertiary folds once bound to S195A trypsin in a crystalline
      lattice are essentially superimposable.

PMID- 18054045
TI  - A theoretical interpretation of the transient sialic acid toxicity of a nanR
      mutant of Escherichia coli.
AB  - This article reports on experimental evidence that an Escherichia coli nanR
      mutant shows inhibited growth in N-acetylneuraminic acid. This effect is
      prevented when inocula are grown in an excess of glucose, but not in an excess of
      glycerol. The nanATEK operon is controlled by catabolite repression, suggesting
      that diminished expression of the nanATEK operon in the presence of glucose
      explains the inocula effects. Neither double nanR-nagC nor nanR dam mutants show
      growth inhibition in the presence of N-acetylneuraminic acid. A theoretical model
      of N-acetylneuraminic acid metabolism (i.e., in particular of the nanATEK and
      nagBACD operons) is presented; the model suggests an interpretation of this
      effect as being due to transient high accumulations of GlcNAc-6P in the cell.
      This accumulation would lead to suppression of central metabolic functions of the
      cell, thus causing inhibited growth. Based on the theoretical model and
      experimental data, it is hypothesised that the nanATEK operon is induced in a two
      step mechanism. The first step is likely to be repressor displacement by N
      acetylneuraminic acid. The second stage is hypothesised to involve Dam
      methylation to achieve full induction.

PMID- 18054044
TI  - PPR336 is associated with polysomes in plant mitochondria.
AB  - The function of pentatricopeptide repeat (PPR) proteins has been associated with
      various post-transcriptional steps of organelle gene expression. Among them,
      translation and its regulation are essential processes. However, in plant
      mitochondria, they are also the steps of gene expression that are the least
      understood. In this study, PPR336 was identified as part of a high-molecular
      weight complex in Arabidopsis mitochondria. PPR336 is an unusual representative
      of the large PPR family because it is relatively short and is characterised by a
      high expression level compared with other PPR proteins. PPR336 defines a small
      subgroup of eight class P PPR proteins that are similar in terms of motif
      organization. Among them, PPR336-like is the closest homolog of PPR336.
      Biochemical analysis has indicated that PPR336 is a strictly mitochondrial
      protein, extrinsically attached to the inner mitochondrial membrane and part of
      an RNase-sensitive complex. Sucrose gradients and polysome destabilisation
      experiments show that PPR336 is associated with ribosomes in plant mitochondria.
      Moreover, in Ppr336/336-like mutants, mitochondrial polysomes of lower molecular
      weight accumulate compared with wild-type plants. Polysome association and these
      unusual features suggest that PPR336 could be involved in a distinctive process,
      possibly translation in plant mitochondria.

PMID- 18054046
TI  - A facile reporter system for the experimental identification of twin-arginine
      translocation (Tat) signal peptides from all kingdoms of life.
AB  - We have developed a reporter protein system for the experimental verification of
      twin-arginine signal peptides. This reporter system is based on the Streptomyces
      coelicolor agarase protein, which is secreted into the growth medium by the twin
      arginine translocation (Tat) pathway and whose extracellular activity can be
      assayed colorimetrically in a semiquantitative manner. Replacement of the native
      agarase signal peptide with previously characterized twin-arginine signal
      peptides from other Gram-positive and Gram-negative bacteria resulted in
      efficient Tat-dependent export of agarase. Candidate twin-arginine signal
      peptides from archaeal proteins as well as plant thylakoid-targeting sequences
      were also demonstrated to mediate agarase translocation. A naturally occurring
      variant signal peptide with an arginine-glutamine motif instead of the consensus
      di-arginine was additionally recognized as a Tat-targeting sequence by
      Streptomyces. Application of the agarase assay to previously uncharacterized
      candidate Tat signal peptides from Bacillus subtilis identified two further
      probable Tat substrates in this organism. This is the first versatile reporter
      system for Tat signal peptide identification.

PMID- 18054047
TI  - Possible mechanisms and controversies of protective effects of risk factors
      against stroke severity.

PMID- 18054048
TI  - The application of genetic algorithms in behavioural ecology, illustrated with a
      model of anti-predator vigilance.
AB  - We develop a genetic algorithm (GA) approach to a well-known model of vigilance
      behaviour in a group of animals. We first demonstrate that the GA approach can
      provide a good match to analytic solutions to the original model. We demonstrate
      that a GA can be used to find the evolutionarily stable strategies in a model
      relevant to behavioural ecology where the fitness of each strategy is determined
      by the frequencies of different strategies in the population. We argue that the
      GA implementation demonstrates the combination of assumptions used to generate
      analytic solution to the original model can only be simultaneously satisfied
      under relatively restrictive conditions on the ecology of the species involved;
      specifically that group membership is very fluid but group size is conserved over
      timescales of individual foraging bouts. We further explore the sensitivity of
      model predictions to alternative choices in the implementation of the GA, and
      present advice for implementation and presentation of similar models. In
      particular, we emphasise the need for care in measuring the predictions of such
      models, so as to capture the intrinsic behaviour of the system and not the
      remnant of often arbitrarily chosen initial conditions. We also emphasise the
      potential for GA models to be more transparent about model assumptions regarding
      underlying biology than analytic models.

PMID- 18054049
TI  - The markup is the model: reasoning about systems biology models in the Semantic
      Web era.
AB  - Metabolic control analysis, co-invented by Reinhart Heinrich, is a formalism for
      the analysis of biochemical networks, and is a highly important intellectual
      forerunner of modern systems biology. Exchanging ideas and exchanging models are
      part of the international activities of science and scientists, and the Systems
      Biology Markup Language (SBML) allows one to perform the latter with great
      facility. Encoding such models in SBML allows their distributed analysis using
      loosely coupled workflows, and with the advent of the Internet the various
      software modules that one might use to analyze biochemical models can reside on
      entirely different computers and even on different continents. Optimization is at
      the core of many scientific and biotechnological activities, and Reinhart made
      many major contributions in this area, stimulating our own activities in the use
      of the methods of evolutionary computing for optimization.

PMID- 18054050
TI  - Prediction of N-linked glycan branching patterns using artificial neural
      networks.
AB  - A model was developed for novel prediction of N-linked glycan branching pattern
      classification for CHO-derived N-linked glycoproteins. The model consists of 30
      independent recurrent neural networks and uses predicted quantities of secondary
      structure elements and residue solvent accessibility as an input vector. The
      model was designed to predict the major component of a heterogeneous mixture of
      CHO-derived glycoforms of a recombinant protein under normal growth conditions.
      Resulting glycosylation prediction is classified as either complex-type or high
      mannose. The incorporation of predicted quantities in the input vector allowed
      for theoretical mutant N-linked glycan branching predictions without initial
      experimental analysis of protein structures. Primary amino acid sequence data
      were effectively eliminated from the input vector space based on neural network
      prediction analyses. This provided further evidence that localized protein
      secondary structure elements and conformational structure may play more important
      roles in determining glycan branching patterns than does the primary sequence of
      a polypeptide. A confidence interval parameter was incorporated into the model to
      enable identification of false predictions. The model was further tested using
      published experimental results for mutants of the tissue-type plasminogen
      activator protein [J. Wilhelm, S.G. Lee, N.K. Kalyan, S.M. Cheng, F. Wiener, W.
      Pierzchala, P.P. Hung, Alterations in the domain structure of tissue-type
      plasminogen activator change the nature of asparagine glycosylation.
      Biotechnology (N.Y.) 8 (1990) 321-325].

PMID- 18054051
TI  - Gallic acid, a metabolite of the antioxidant propyl gallate, inhibits gap
      junctional intercellular communication via phosphorylation of connexin 43 and
      extracellular-signal-regulated kinase1/2 in rat liver epithelial cells.
AB  - Propyl gallate and its metabolite, gallic acid, are widely used as antioxidants
      in the food industry, but they have been shown to exhibit liver toxicity and
      enhance carcinogenesis. In the present study, we investigated the possible
      undesirable effects of propyl gallate and gallic acid on gap junctional
      intercellular communication (GJIC), inhibition of which is closely linked to
      carcinogenesis. Gallic acid and propyl gallate exhibited dose-dependent free
      radical-scavenging activities as determined by 1,1-diphenyl-2-picrylhydrazyl- or
      2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)-radical-scavenging assays,
      and the free-radical-scavenging activity of gallic acid was stronger than that of
      propyl gallate. However, using WB-F344 rat liver epithelial cells, gallic acid
      inhibited GJIC in a dose-dependent manner, while propyl gallate had no
      significant effect compared with untreated controls. The gallic-acid-induced
      inhibition of GJIC was reversible, with a recovery of nearly 65% after 120 min.
      Gallic acid induced the phosphorylation of connexin 43 (Cx43) and phosphorylation
      of extracellular-signal-regulated kinase1/2 (ERK1/2). The gallic-acid-induced
      inhibition of GJIC was attenuated by treatment with mitogen-activated protein
      kinase kinase inhibitors (U0126 and PD098059). U0126 blocked the gallic-acid
      induced phosphorylation of Cx43 and ERK1/2, indicating that the gallic-acid
      induced inhibition of GJIC is mediated by phosphorylation of Cx43 via activation
      of ERK1/2. In addition, gallic-acid-induced inhibition of GJIC was protected by
      ascorbic acid and quercetin, which might represent a simple example of the
      different effects of natural antioxidants in carcinogenesis.

PMID- 18054052
TI  - The cannabinoid antagonist AM251 attenuates nicotine self-administration and
      nicotine-seeking behaviour in rats.
AB  - The cannabinoid receptor subtype (CB1) antagonist rimonabant (SR141716) has been
      shown to decrease nicotine self-administration and attenuate nicotine-evoked
      dopamine release in the nucleus accumbens; effects that support recent findings
      on its clinical efficacy as a smoking cessation aid. The present experiments aim
      to advance our understanding on the role of CB1 receptors in rodent models of
      nicotine dependence. AM251, a selective antagonist at CB1 receptors dose
      dependently (1, 3 and 10mg/kg IP) suppressed intravenous nicotine (0.03mg/kg per
      infusion) self-administration in rats during three successive days of pre
      treatment. This reduction was short lasting since behaviour was reinstated by
      suspending AM251 pre-treatment. This was relatively specific to nicotine self
      administration since the profile of these reductions produced by AM251 was
      significantly different from the responses maintained by food pellets. In a model
      of nicotine-seeking behaviour, rats that had been extinguished by removal of
      nicotine and associated cues, and presented with a priming dose of nicotine
      (0.2mg/kg SC) with the cues, showed robustly reinstated responses to nicotine
      seeking behaviour. Acute pre-treatment with AM251 (1-10mg/kg IP) dose-dependently
      attenuated the reinstatement effects produced by nicotine and the contingently
      presented cues. These preclinical findings support the use of rimonabant as a
      smoking cessation aid and highlight the CB1 receptor as a viable target to
      control intake of nicotine and prevent relapse.

PMID- 18054053
TI  - Effects of aripiprazole/OPC-14597 on motor activity, pharmacological models of
      psychosis, and brain activity in rats.
AB  - Aripiprazole (OPC-14597) is an antipsychotic with a unique pharmacology as a
      dopamine D2 receptor partial agonist, which has been demonstrated to reduce
      symptoms of schizophrenia. To further profile this compound in preclinical
      models, we examined aripiprazole-induced activity changes as measured by
      pharmacological magnetic resonance imaging (MRI) and characterized the drug in
      several rodent models of motor behaviors and of psychosis. Continuous arterial
      spin labeling MRI measuring blood perfusion (as an indirect measure of activity)
      reveals that aripiprazole dose-dependently decreased brain activity in the
      entorhinal piriform cortex, perirhinal cortex, nucleus accumbens shell, and
      basolateral amygdala. While no deficits were observed in the rotarod test for
      motor coordination in the simpler (8 RPM) version, in the more challenging
      condition (16 RPM) doses of 10 and 30mg/kg i.p. produced deficits. Catalepsy was
      seen only at the highest dose tested (30mg/kg i.p.) and only at the 3 and 6h time
      points, not at the 1h time point. In pharmacological models of psychosis, 1
      30mg/kg aripiprazole i.p. effectively reduced locomotor activity induced by
      dopamine agonists (amphetamine and apomorphine), NMDA antagonists (MK-801 and
      phencyclidine (PCP)), and a serotonin agonist (2,5-dimethoxy-4-iodoamphetamine
      (DOI)). However, aripiprazole reversed prepulse inhibition deficits induced by
      amphetamine, but not by any of the other agents tested. Aripiprazole alters brain
      activity in regions relevant to schizophrenia, and furthermore, has a
      pharmacological profile that differs for the two psychosis models tested and does
      not match the typical or atypical psychotics. Thus, D2 partial agonists may
      constitute a new group of antipsychotics.

PMID- 18054055
TI  - Measurement of the digit lengths and the anogenital distance in mice.
AB  - In humans, research has demonstrated the ratio of the 2nd to 4th digit lengths
      (2D:4D) are: (i) sexually dimorphic with males having a lower ratio than females,
      the latter having near equidistant lengths [J. Manning, D. Scutt, J. Wilson, & D.
      Lewis-Jones, (1998). The ratio of 2nd to 4th digit length: a predictor of sperm
      numbers and concentrations of testosterone, luteinizing hormone and oestrogen.
      Hum Reprod. 13(11):3000-3004], and are theorized to be (ii) determined in utero
      during gestational development [J. Manning, & P. Bundred, (2000). The ratio of
      2nd to 4th digit length: a new predictor of disease predisposition? Med
      Hypotheses. 54(5):855-857], and (iii) correlated with prenatal androgen levels
      [J. Manning, & P. Bundred, (2000). The ratio of 2nd to 4th digit length: a new
      predictor of disease predisposition? Med Hypotheses. 54(5):855-857; J. Manning,
      R. Trivers, D. Singh, & R. Thornhill, (1999). The mystery of female beauty.
      Nature. 399:214-215; T. Williams, M. Pepitone, S. Christensen, B. Cooke, A.
      Huberman, N. Breedlove, et al., (2000). Finger-length ratios and sexual
      orientation: measuring people's finger patterns may reveal some surprising
      information. Nature. 404:455-456]. These phenotypes correspond to the hormonal
      effects of testosterone (i.e. androgens) in utero in both sexes. In mice,
      testosterone in utero is associated in males and females with the anogenital
      distance (AGD), a phenotype where AGD is greater in males and females contiguous
      with two males (2M) have a masculinized AGD phenotype whereas those juxtaposed to
      fewer males, one or zero (1M or 0M), have a more feminine phenotype, i.e. shorter
      AGD [F. vom Saal, & F. Bronson, (1980). Sexual characteristics of adult female
      mice are correlated with their blood testosterone levels during prenatal
      development. Science. 208:597-599; R. Gandelman, F. vom Saal, & J. Reinisch,
      (1977). Contiguity to male foetuses affects morphology and behaviour of female
      mice. Nature. 266:722-724; A. Hotchkiss, & J. Vandenbergh, (2005). The anogenital
      distance index of mice (Mus musculus domesticus): an analysis. Contem Top Lab
      Anim Sci. 44(4):46-48; C. Kinsley, J. Miele, C. Wagner, L. Ghiraldi, J. Broida,
      B. Svare, (1986). Prior intrauterine position influences body weight in male and
      female mice. Horm Behav. 20:201-211; S. Graham, R. Gandelman, (1986). The
      expression of ano-genital distance data in the mouse. Physiol Behav. 36(1):103
      104; B. Ryan, & J. Vandenbergh, (2002). Intrauterine position effects. Neurosci
      Biobehav Rev. 26(6):665-678; J. Vandenbergh, & C. Huggett, (1995). The anogenital
      distance index, a predictor of the intrauterine position effects on reproduction
      in female house mice. Lab Anim Sci. 45(5):567-573]. Furthermore, in humans AGD is
      sexually dimorphic with neonate males having a greater distance than females [E.
      Salazar-Martinez, P. Romano-Riquer, E. Yanez-Marquez, M. Longnecker, M. Hernandez
      Avila, (2004). Anogenital distance in human male and female newborns: a
      descriptive, cross-sectional study. Environmental Health: A Global Access Science
      Source. 2004:3:(8) (doi:10.1186/1476-069X-3-8) [12]]. Recently, research has
      concluded that the digit lengths of mice have the same phenotypic pattern seen in
      humans, with the 2D:4D ratio being sexually dimorphic, i.e. lower in males and
      greater in females [W. Brown, C. Finn, & S. Breedlove, (2002). Sexual dimorphism
      in digit-length ratios of laboratory mice. Anat Rec. 267(3):231-234; J. Manning,
      M. Callow, & P. Bundred, (2003). Finger and toe ratios in humans and mice:
      implications for the aetiology of diseases influenced by HOX genes. Med
      Hypotheses. 60(3):340-343; W. Brown, C. Finn, & S. Breedlove, (2001). A sex
      difference in the digit length ratio in mice. Horm Behav. 39:325]. The following
      study was conducted to determine whether the digit length ratios in mice are
      correlated with a known in utero testosterone-dependent effect, the distance from
      the anus to the genital papilla, the AGD. The results of the experiment
      demonstrate that there is no correlation between AGD and the 2D:4D ratio in mice
      of either sex. Furthermore, no sexual dimorphism in the digit lengths was found
      as opposed to previous studies [W. Brown, C. Finn, & S. Breedlove, (2002). Sexual
      dimorphism in digit-length ratios of laboratory mice. Anat Rec. 267(3):231-234;
      J. Manning, M. Callow, & P. Bundred, (2003). Finger and toe ratios in humans and
      mice: implications for the aetiology of diseases influenced by HOX genes. Med
      Hypotheses. 60(3):340-343; W. Brown, C. Finn, & S. Breedlove, (2001). A sex
      difference in the digit length ratio in mice. Horm Behav. 39:325]. Although
      testosterone has been implicated in the digit length ratios, the present study
      would suggest that androgens do not have a causal relationship with testosterone
      dependent phenotypes [J. Manning, D. Scutt, J. Wilson, & D. Lewis-Jones, (1998).
      The ratio of 2nd to 4th digit length: a predictor of sperm numbers and
      concentrations of testosterone, luteinizing hormone and oestrogen. Hum Reprod.
      13(11):3000-3004; J. Manning, & P. Bundred, (2000). The ratio of 2nd to 4th digit
      length: A new predictor of disease predisposition?. Med Hypotheses. 54(5):855
      857; J. Manning, R. Trivers, D. Singh, & R. Thornhill, (1999). The mystery of
      female beauty. Nature. 399:214-215]. The attribution of nature (i.e. genetic) and
      nurture (i.e. environment) in the development of life (i.e. resultant phenotype)
      is exceedingly complex and the correlation of one trait to another physical
      characteristic does not preclude there is a causal relationship.

PMID- 18054054
TI  - Effects of sex hormones on associative learning in spontaneously hypertensive
      rats.
AB  - Pavlovian conditioning of a visual stimulus paired with food was examined in
      spontaneously hypertensive rats (SHR), which are a commonly used model for
      Attention-Deficit/Hyperactivity Disorder (ADHD), and in Wistar rats (normoactive
      control). In gonadally intact rats of both strains, males spent more time in the
      food cup following onset of the light than did females, indicating a stronger
      association of the conditioned stimulus (CS) with reward. Gonadectomy carried out
      in adulthood affected conditioning differently in the two strains. In Wistar
      rats, gonadectomy had no effect on conditioned responding in females, but reduced
      conditioned responding in males, effectively eliminating the sex difference in
      behavior. This result suggests that circulating androgens in male Wistar rats
      normally aid conditioning in this task. In contrast, gonadectomy enhanced
      conditioning in both sexes in the SHR rats, indicating that androgens and/or
      estrogens impair conditioned associations in this strain. These data indicate
      that gonadal steroids can influence conditioning in rats and that the valence of
      steroid action on this behavior is strain-dependent. To the extent that SHR
      serves as a model of ADHD in humans, the influence of steroids on associative
      learning may play a role in the expression of ADHD-like behaviors.

PMID- 18054056
TI  - Insecticide susceptibility and vector status of natural populations of Anopheles
      arabiensis from Sudan.
AB  - Species composition, blood meal source, sporozoite infection rate, insecticide
      resistance and the kdr mutations were investigated in the Anopheles gambiae
      complex from 13 sentinel sites in central Sudan. Species identification revealed
      that 89.5% of 960 specimens were A. arabiensis. Of 310 indoor resting females,
      88.1% were found to have fed on humans, while 10.6% had fed on bovines. The
      overall sporozoite infection rate from the five localities tested was 2.3%,
      ranging from 0 to 5.5%. Insecticide susceptibility bioassay results showed 100%
      mortality on bendiocarb, 54.6-94.2% on permethrin, 55.4-99.1% on DDT and 76.8
      100% on malathion. The kdr analysis by PCR and sequencing revealed the presence
      of the Leu-Phe mutation in both permethrin and DDT bioassays. There was no
      significant difference in the frequency of kdr (P>0.05) between dead and
      surviving specimens. These findings have serious implications for the malaria
      control programmes in Gezira and Sennar states.

PMID- 18054057
TI  - Control of neurocysticercosis by routine medical and veterinary services.
AB  - Taenia solium neurocysticercosis and ocular cysticercosis are two of the most
      devastating parasitic infections, which need to be controlled for medical and
      economic reasons. This paper discusses why control measures are not implemented
      adequately in endemic areas and proposes simple operational interventions, based
      on focus-oriented chemotherapy of T. solium taeniasis using existing health care
      infrastructure and improved collaboration between medical and veterinary
      services. These interventions can be quickly and easily implemented (irrespective
      of other applicable control measures), with medical and veterinary staff being
      adequately trained, and safe, effective and cheap taenicides made available.

PMID- 18054058
TI  - Gastrointestinal pathology in the University Teaching Hospital, Lusaka, Zambia:
      review of endoscopic and pathology records.
AB  - There is a shortage of information on the epidemiology of digestive disease in
      developing countries. In the belief that such information will inform public
      health priorities and epidemiological comparisons between different geographical
      regions, we analysed 2132 diagnostic upper gastrointestinal endoscopy records
      from 1999 to 2005 in the University Teaching Hospital, Lusaka, Zambia. In order
      to clarify unexpected impressions about the age distribution of cancers, a
      retrospective analysis of pathology records was also undertaken. No abnormality
      was found in 31% of procedures, and in 42% of procedures in children. In patients
      with gastrointestinal haemorrhage, the common findings were oesophageal varices
      (26%), duodenal ulcer (17%) and gastric ulcer (12%). Gastrointestinal malignancy
      was found in 8.8% of all diagnostic procedures, in descending order of frequency:
      gastric adenocarcinoma, oesophageal squamous carcinoma, Kaposi's sarcoma,
      oesophageal adenocarcinoma. Data from endoscopy records and pathology records
      strongly suggest that the incidence in adults under the age of 45 years is higher
      than in the USA or UK, and pathology records suggest that this effect is
      particularly marked for colorectal carcinoma.

PMID- 18054059
TI  - Neutralization of two North American coral snake venoms with United States and
      Mexican antivenoms.
AB  - Elapid snakes throughout the world are considered very lethal, containing
      neurotoxic venoms that affect the nervous system. When humans are envenomated it
      is considered a serious medical emergency, and antivenom is the main form of
      treatment considered, in spite of the fact that some patients may only survive
      under intensive therapy treatment such as respiratory support. Coral snakes are
      part of the family Elapidae and envenomations by these snakes are very low (<2%
      of total snakebites) in most countries from southeastern United States to
      Argentina. In the United States, there are only two species of coral snakes of
      medical importance that belong to the Micrurus genera: Micrurus fulvius fulvius
      (Eastern coral snake) and Micrurus tener tener (Texas coral snake). In 2006,
      Wyeth pharmaceutical notified customers that the production of the North American
      coral snake antivenin (NACSA) in the US was discontinued and adequate supplies
      were available to meet historical needs through the end of October 2008; and
      therefore, it is of utmost important to consider other antivenoms as alternatives
      for the treatment of coral snake envenoming. One logical alternative is the coral
      snake antivenom, Coralmyn, produced by the Mexican company, Bioclon. In order to
      compare neutralization between NACSA and Coralmyn antivenoms with the North
      American coral snake venoms, the venom lethal doses (LD(50)) and antivenom
      effective doses (ED(50)) were determined in 18-20 g, female, BALB/c mice.
      Additionally, venom comparisons were determined through a non-reduced SDS-PAGE
      for M.f.fulvius, M.t.tener and the Mexican coral snake venom, Micrurus
      nigrocinctus nigrocinctus. Coralmyn antivenom was able to effectively neutralize
      three LD(50) doses of all venom from both M.t.tener and M.f.fulvius, while Wyeth
      antivenom only neutralized M.f.fulvius venom and was not effective in
      neutralizing three LD(50) doses of M.t.tener venom. Coralmyn is effective in the
      neutralization of both clinically important coral snake venoms in the US.

PMID- 18054060
TI  - Synthesis and characterization of huwentoxin-IV, a neurotoxin inhibiting central
      neuronal sodium channels.
AB  - Our previous work demonstrated that huwentoxin-IV was an inhibitor cystine knot
      peptide from Chinese tarantula Ornithoctonus huwena venom that blocked
      tetrodotoxin-sensitive voltage-gated sodium channels from mammalian sensory
      neurons [Peng, K., Shu, Q., Liu, Z., Liang, S., 2002. Function and solution
      structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium
      channel antagonist from Chinese bird spider Selenocosmia huwena. J. Biol. Chem.
      277(49), 47564-47571]. However, the actions of the neurotoxin on central neuronal
      sodium channels remain unknown. In this study, we chemically synthesized native
      huwentoxin-IV and found that sodium channel isoforms from rat hippocampus neurons
      were also sensitive to native and synthetic toxins, but the toxin-binding
      affinity (IC(50) approximately 0.4 microM) was 12-fold lower than to peripheral
      isoforms. The blockade by huwentoxin-IV could be reversed by strong
      depolarization due to the dissociation of toxin-channel complex as observed for
      receptor site 3 toxins. Moreover, small unilamellar vesicle-binding assays showed
      that in contrast to ProTx-II from the tarantula Thrixopelma pruriens, huwentoxin
      IV almost lacked the ability to partition into the negatively charged and neutral
      phospholipid bilayer of artificial membranes. These findings indicated that
      huwentoxin-IV was a sodium channel antagonist preferentially targeting peripheral
      isoforms via a mechanism quite different from ProTx-II.

PMID- 18054061
TI  - Identification from diverse mammalian poxviruses of host-range regulatory genes
      functioning equivalently to vaccinia virus C7L.
AB  - Vaccinia virus (VACV) C7L is a host-range gene that regulates cellular tropism of
      VACV. Distantly related C7L homologues are encoded by nearly all mammalian
      poxviruses, but whether they are host-range genes functioning similar to VACV C7L
      has not been determined. Here, we used VACV as a model system to analyze five
      different C7L homologues from diverse mammalian poxviruses for their abilities to
      regulate poxvirus cellular tropism. Three C7L homologues (myxoma virus M63R, M64R
      and cowpox virus 020), when expressed with an epitope tag and from a VACV mutant
      lacking the host-range genes K1L and C7L (vK1L-C7L-), failed to support
      productive viral replication in human and murine cells. In nonpermissive cells,
      these viruses did not synthesize viral late proteins, expressed a reduced level
      of the early protein E3L, and were defective at suppressing cellular PKR
      activation. In contrast, two other C7L homologues, myxoma virus (MYXV) M62R and
      yaba-like disease virus (YLDV) 67R, when expressed with an epitope tag and from
      vK1L(-)C7L(-), supported normal viral replication in human and murine cells and
      restored the ability of the virus to suppress PKR activation. Furthermore, M62R
      rescued the defect of vK1L(-)C7L(-) at replicating and disseminating in mice
      following intranasal inoculation. These results show that MYXV M62R and YLDV 67R
      function equivalently to C7L at supporting VACV replication in mammalian hosts
      and suggest that a C7L-like host-range gene is essential for the replication of
      many mammalian poxviruses in mammalian hosts.

PMID- 18054062
TI  - Persistent transcription of a nonintegrating mutant of simian immunodeficiency
      virus in rhesus macrophages.
AB  - A nonintegrating mutant, SIVsmD116N, was derived from the infectious pathogenic
      SIVsmE543-3 clone by introducing an Asp (D) to Asn (N) mutation into the
      catalytic domain of integrase. Although SIVsmD116N generated all viral proteins
      following transfection, cell-free virus did not productively infect CEMx174
      cells, macaque peripheral blood mononuclear cells (PBMCs) or monocyte-derived
      macrophages (MDM). Viral DNA and transcripts were observed transiently in
      SIVsmD116N-infected CEMx174 cells and macaque PBMC but persisted in MDM for as
      long as 20 days. Circular forms of viral DNA were detected but there was no
      evidence of integration detected by Alu PCR. We found that SIV D116N mutant
      remained transcriptionally active and expressed low levels of viral proteins
      persistently in MDM. These data are consistent with a role for macrophages as a
      persistent latent reservoir for AIDS viruses. The capacity of nonintegrating SIV
      to persistently generate viral products in macrophages suggests that
      nonintegrating lentiviral vectors could be engineered to efficiently and safely
      express proteins for vaccine purposes.

PMID- 18054064
TI  - Mutagenesis studies on TenA: a thiamin salvage enzyme from Bacillus subtilis.
AB  - TenA catalyzes the hydrolysis of 4-amino-5-aminomethyl-2-methylpyrimidine and
      participates in the salvage of base-degraded thiamin. Here, we describe
      mutagenesis of the active site of TenA guided by structures of the enzyme
      complexed to a substrate analog and to the product. Catalytic roles for each of
      the active site residues are identified and a mechanism for the reaction is
      described.

PMID- 18054065
TI  - Formation of chlorinated phenols, dibenzo-p-dioxins, dibenzofurans, benzenes,
      benzoquinnones and perchloroethylenes from phenols in oxidative and copper (II)
      chloride-catalyzed thermal process.
AB  - Formation of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), and chlorinated phenols on CuCl(2) from unsubstituted
      phenol and three monochlorophenols was studied in a flow reactor over a
      temperature range of 100-425 degrees C. Heated nitrogen gas streams containing
      8.0% oxygen were used as carrier gas. The 0.00024mol of unsubstituted phenol and
      0.00039mol of each monochlorophenol were passed through a 1g and 1cm SiO(2)
      particle containing 0.5% (Cu by mass) CuCl(2). Chlorination preferentially
      occurred on ortho-(2, 6) and para-(4) positions. Chlorination increased up to 200
      degrees C, and thereafter decreased as temperature increased. Chlorination of
      phenols plays an important role in the formation of the more chlorinated PCDD/Fs.
      Chlorinated benzenes are formed possibly from both chlorination of benzene and
      chlorodehydroxylation of phenols. Chlorinated phenols with ortho chlorine formed
      PCDD products, and major PCDD products were produced via loss of one chlorine.
      For PCDF formation, at least one unchlorinated ortho carbon was required.

PMID- 18054063
TI  - Specific in vivo expression in type II pneumocytes of the Jaagsiekte sheep
      retrovirus long terminal repeat in transgenic mice.
AB  - Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary
      adenocarcinoma, a transmissible lung cancer in sheep. Previous experiments in
      differentiated murine tissue culture cell lines suggested that the disease
      specificity of JSRV for secretory lung epithelial cells (type II pneumocytes an
      Clara cells) reflects transcriptional specificity of the viral long terminal
      repeat (LTR) for these cells. To test this in vivo, transgenic mice carrying the
      bacterial beta-galactosidase (beta-Gal) gene driven by the JSRV LTR were
      generated. Two transgenic lines showed beta-Gal expression in the lungs but not
      other tissues of F1 animals, although transgene silencing in subsequent
      generations was a major problem. The cells expressing the transgene were
      identified by two- and three-color immunofluorescence for marker proteins of type
      II pneumocytes (surfactant protein C [SPC]) and Clara cells (CC10) as well as for
      a T7 gene 10 epitope present in the beta-Gal reporter. F1 animals from both lines
      showed transgene expression in type II pneumocytes, but somewhat surprisingly not
      in Clara cells. Expression was not detected in bronchiolo-alveolar stem cells
      (BASCs) either. These results indicate that the JSRV LTR is specifically active
      in type II pneumocytes in the mouse lung, which is consistent with the fact that
      JSRV-induced OPA tumors in sheep largely have phenotypic markers of type II
      pneumocytes.

PMID- 18054066
TI  - Variation and modalities of growth and development of the temporal bone
      pneumatization in Neandertals.
AB  - The temporal bone is used frequently to determine taxonomic affinities as it
      contains several features that differentiate Neandertals from anatomically modern
      Homo sapiens. However, only little information is available about temporal bone
      pneumatization in Neandertals. This study provides descriptions and comparisons
      of the disposition and the extensiveness of the pneumatization of the temporal
      bone in large samples of Neandertal specimens of different geological and
      developmental ages (25 individuals and 33 temporal bones from the sites of Engis,
      Krapina, La Chapelle aux Saints, La Ferrassie, La Quina, Pech de l'Aze, and Spy).
      Although temporal bone pneumatization shows some individual variability, a
      similar pattern of distribution is found in all adult Neandertal individuals from
      Krapina and Western Europe. Pneumatization is restricted mainly to most parts of
      the petromastoid areas. We also retrace for the first time the modalities of
      growth and development of this pneumatization in Neandertals. Finally, this study
      provides new information about possible correlations between the extension and
      position of temporal bone pneumatization and some of the morphological features
      used to characterize the temporal bone of the Neandertals. These latter features
      include the relatively low and short temporal squama, the robust zygomatic
      process with a relatively marked lateral projection, the strong supramastoid
      crest, the significant thickness of the tympanic part of the temporal bone, and
      the relatively small mastoid process and large juxtamastoid eminence. Our results
      suggest that the development of pneumatization in Neandertals is related to
      available space and to temporal bone morphology. Moreover, it appears that the
      development of pneumatization does not play an active role in determining the
      morphology of the apomorphic features of the temporal bone in Neandertals.

PMID- 18054067
TI  - Ammonia volatilization from a paddy field following applications of urea: rice
      plants are both an absorber and an emitter for atmospheric ammonia.
AB  - Ammonia (NH(3)) volatilization from a paddy field following applications of urea
      was measured. Two lysimeters of Gray Lowland soil with a pH (H(2)O) of 5.7 were
      used for the experiment. Urea was applied at a rate of 50 kg N ha(-1) by
      incorporation as the basal fertilization (BF) and at rates of 30 and 10 kg N ha(
      1) by top-dressing as the first (SF1) and second (SF2) supplemental
      fertilizations, respectively. Two wind tunnels per lysimeter were installed just
      after BF; one was transplanted with rice plants (PR plot), and the other was
      without rice plants (NR plot). Weak volatilization was observed at the PR plots
      after BF. By contrast, strong volatilization was observed at the PR plots after
      SF1 with a maximum flux of 150 g N ha(-1) h(-1); however, almost no
      volatilization was observed after SF2. The NH(3) volatilization loss accounted
      for 2.1%, 20.9%, 0.5%, and 8.2% of the applied urea at each application, BF, SF1,
      SF2, and the total application, respectively, for which only the net fluxes as
      volatilization were accumulated. The NH(3) volatilization fluxes from the paddy
      water surface (F(vol)) at the NR plots were estimated using a film model for its
      verification. After confirmation of good correlation, the film model was applied
      to estimate F(vol) at the PR plots. The NH(3) exchange fluxes by rice plants
      (F(ric)) were obtained by subtracting F(vol) from the observed net NH(3) flux.
      The derived F(ric) showed that the rice plants emitted NH(3) remarkably just
      after SF1 when a relatively high rate of urea was applied, although they absorbed
      atmospheric NH(3) in the other periods. In conclusion, rice plants are
      essentially an absorber of atmospheric NH(3); however, they turn into an emitter
      of NH(3) under excess nutrition of ammoniacal nitrogen.

PMID- 18054068
TI  - Is soluble CD40 ligand a mediator of angiogenesis in patients with coronary
      artery disease?
AB  - BACKGROUND: In cardiovascular disease, soluble CD40 ligand (sCD40L) has been
      associated with an adverse prognosis. Angiogenesis has been implicated in the
      progression of coronary artery disease (CAD) and sCD40L has pro-angiogenic
      effects in vitro. Angiogenesis itself is regulated by many mediators, such as
      vascular endothelial growth factor (VEGF) and the angiopoietins (Ang). Ang-1
      promotes vascular maturation whilst Ang-2 destabilises the blood vessel and
      permits vascular growth with VEGF. Hence, selective elevation of VEGF and Ang-2
      suggest a state of vascular plasticity and increased angiogenesis. We
      hypothesised raised plasma levels of VEGF and Ang-2, but not Ang-1, and
      correlations with raised sCD40L levels and CAD severity/collateralisation in
      patients with CAD. METHODS: We recruited 153 patients attending diagnostic
      angiography for CAD and 47 healthy controls. Patients with previous
      revascularisation or unequivocally normal angiograms were excluded. The coronary
      atheroma score (CAS) and coronary stenosis score (CSS), and the presence of
      collaterals, were assessed by 2 blinded observers. Plasma sCD40L, VEGF, Ang-1 and
      -2 levels were measured by ELISA. RESULTS: Plasma levels of sCD40L, VEGF and Ang
      2, but not Ang-1, were higher in CAD patients compared to controls. Both plasma
      VEGF (r=0.526, p<0.001) and Ang-2 (r=0.429, p<0.001) were correlated with sCD40L,
      but not with CAS, CSS or collateralisation. On stepwise multivariate regression
      analysis, plasma sCD40L was an independent predictor of plasma VEGF (p=0.002),
      and Ang-2 (p<0.001) levels. CONCLUSION: These data suggest abnormal indices of
      angiogenesis in CAD, which may be associated with increased CD40-CD40L
      interactions in patients with CAD. Plasma sCD40L, VEGF and Ang-2 levels were not
      correlated to angiographic CAD/collateralisation.

PMID- 18054069
TI  - Relevance of hemostasis on restenosis in clinically stable patients undergoing
      elective PTCA.
AB  - BACKGROUND: Secondary coronary thrombus formation is considered to be co-factor
      in the pathogenesis of restenosis after percutaneous transluminal coronary
      angioplasty (PTCA). Therefore systemic factors indicating a hypercoagulable
      disease state may be relevant for the process of coronary renarrowing. Even
      though experimental data suggest that in particular thrombin may be of major
      relevance for restenosis induced by mechanical injury, only little clinical data
      has been presented so far. METHODS AND RESULTS: In 60 consecutive patients, who
      had been clinical stable for at least 2 months, and who underwent elective and
      primarily successful PTCA, follow-up films were evaluated by means of
      quantitative coronary angiography in respect to a categorical and a continuous
      definition of restenosis, luminal narrowing >50% and late luminal loss
      respectively. Of the chosen laboratory variables prothrombin fragment 1+2 (1.3+/
      0.5 vs. 0.9+/-0.4 mmol/l, p<0.001) red blood cell aggregation at low shear stress
      (13.5+/-2.9 vs. 11.6+/-2.8 units, p<0.05), and plasminogen-activator inhibitor
      (3.7+/-1.8 vs. 5.3+/-3.2 U/ml p<0.05) differentiated between patients with (n=18)
      and without restenosis (n=42). Late luminal loss correlated positively with
      prothrombin fragment 1+2 (r=0.41, p<0.001), plasminogen-activator inhibitor (r= 
      0.28, p<0.05) and plasmin-alpha2-antiplasmin complex (r=0.39, p<0.01).
      CONCLUSIONS: A hypercoagulable disease state and in particular thrombin
      generation characterize a high-risk group prone for restenosis in clinically
      stable coronary artery disease.

PMID- 18054070
TI  - The effects of non-genomic glucocorticoid mechanisms on bodily functions and the
      central neural system. A critical evaluation of findings.
AB  - Mounting evidence suggests that--beyond the well-known genomic effects-
      glucocorticoids affect cell function via non-genomic mechanisms. Such mechanisms
      operate in many major systems and organs including the cardiovascular, immune,
      endocrine and nervous systems, smooth and skeletal muscles, liver, and fat cells.
      Non-genomic effects are exerted by direct actions on membrane lipids (affecting
      membrane fluidity), membrane proteins (e.g. ion channels and neurotransmitter
      receptors), and cytoplasmic proteins (e.g. MAPKs, phospholipases, protein
      kinases, etc.). These actions are mediated by the glucocorticoids per se or by
      the proteins dissociated from the liganded glucocorticoid receptor complex. The
      MR and GR also activate non-genomic mechanisms in certain cases. Some effects of
      glucocorticoids are shared by a variety of steroids, whereas others are more
      selective. Moreover, "ultra-selective" effects-mediated by certain
      glucocorticoids only-were also shown. Disparate findings suggest that non-genomic
      mechanisms also show "demand-specificity", i.e. require the coincidence of two or
      more processes. Some of the non-genomic mechanisms activated by glucocorticoids
      are therapeutically relevant; moreover, the "non-genomic specificity" of certain
      glucocorticoids raises the possibility of therapeutic applications. Despite the
      large body of evidence, however, the non-genomic mechanisms of glucocorticoids
      are still poorly understood. Criteria for differentiating genomic and non-genomic
      mechanisms are often loosely applied; interactions between various mechanisms are
      unknown, and non-genomic mechanism-specific pharmacological (potentially
      therapeutic) agents are lacking. Nevertheless, the discovery of non-genomic
      mechanisms is a major breakthrough in stress research, and further insights into
      these mechanisms may open novel approaches for the therapy of various diseases.

PMID- 18054071
TI  - Hormonal changes in spontaneous and aglepristone-induced parturition in dogs.
AB  - To increase our understanding of the endocrine changes associated with
      parturition in dogs, plasma concentrations of progesterone (P4), 15
      ketodihydroprostaglandin F(2alpha) (PGFM), estradiol-17-beta (E2beta), cortisol,
      ACTH, prolactin (PRL), LH, and FSH were measured in six spontaneously whelping
      bitches and in six bitches in which parturition was induced with the progesterone
      receptor blocker aglepristone on day 58 of pregnancy. Expulsion of pups in the
      induced group took place in the presence of P4 concentrations that were still
      elevated. PGFM concentrations increased before parturition in both groups, but
      levels were lower in the induced bitches. PGFM levels reached a maximum in both
      groups during parturition and quickly decreased in the spontaneously whelping
      group after parturition, but remained elevated in the induced group. In both
      groups, cortisol concentrations reached similar maximum levels during the last 30
      h before the onset of expulsion. During the 3 days postpartum, cortisol
      concentrations were higher in the induced group. The highly variable ACTH
      concentrations did not differ significantly throughout the study within or
      between groups. In both groups, E2beta concentrations decreased and PRL
      concentrations increased between the late gestational period and the 30-h period
      before parturition. Concentrations of both LH (spontaneously whelping group) and
      FSH (both groups) decreased between late gestation and the postpartum period. The
      results of this study illustrate the hormonal changes around parturition in the
      bitch, and reveal that aglepristone-induced parturition is associated with still
      incomplete luteolysis, an altered PGFM profile, and elevated postpartum cortisol
      concentrations as compared with spontaneously whelping dogs.

PMID- 18054072
TI  - Linking pollution induced community tolerance (PICT) and microbial community
      structure in chronically metal polluted estuarine sediments.
AB  - We tested the ability of pollution induced community tolerance (PICT) to detect
      the effects of chronic metal pollution on estuarine sediment microbial
      communities, along a gradient spanning two orders of magnitude in metal
      concentrations. In tandem, we investigated the associated microbial community
      structure using terminal restriction fragment length polymorphism (T-RFLP).
      Tolerance of microbes to Cu, measured as IC50 (inhibitory concentration 50%), was
      strongly correlated with pore water Cu concentration (r(2)=0.842). No strong
      correlation existed for other metals tested, highlighting the ability of PICT to
      identify the pollutant causing a toxic effect. There was no correlation between
      microbial community structure and community tolerance to metals tested, but
      analysis of community structure did provide some information on reasons for
      observed PICT response. PICT methodology used here provided a greater strength
      and consistency of association with pollutant concentration compared to microbial
      community structure and can be recommended as a sensitive indicator of metal
      pollution on estuarine sediment microbial communities.

PMID- 18054073
TI  - Hemagglutinating activity and conformation of a lactose-binding lectin from
      mushroom Agrocybe cylindracea.
AB  - A lactose-binding lectin (Agrocybe cylindracea Lectin, ACL) purified from
      fruiting bodies of the mushroom A. cylindracea was investigated to determine the
      hemagglutinating activity and conformation changes after chemical modification,
      removal of metal ion and treatment at different temperatures and pH. ACL
      agglutinated both rabbit and human erythrocytes and its hemagglutinating activity
      could be inhibited by lactose. This lectin was stable in the pH range of 6-9 and
      temperature up to 60 degrees C. Fluorescence quenching and modification of
      tryptophan residues indicated that there were about two tryptophan residues in
      ACL molecule and one of them might be located on the surface, while the other was
      buried in the hydrophobic shallow groove near the surface. Chemical modification
      of serine/threonine and histidine showed that the partial necessity of these
      residues for the hemagglutinating activity of ACL. However, modifications of
      arginine, tyrosine and cysteine residues had no effect on its agglutinating
      activity.

PMID- 18054074
TI  - Influence of electrospun collagen on wound contraction of engineered skin
      substitutes.
AB  - The treatment of massive full-thickness burns with engineered skin substitutes
      has shown promise in clinical trials. The majority of skin substitutes are
      comprised of fibroblasts and/or keratinocytes on collagen scaffolds, commonly
      generated by freeze drying which can generate significant structural
      heterogeneity. Electrospinning may generate collagen scaffolds with greater
      homogeneity. Skin substitutes were fabricated using either freeze-dried (FD) or
      electrospun (ES) collagen scaffolds. Cell distribution, proliferation,
      organization, and maturation were assessed on each scaffold type in vitro, and
      engraftment and healing of full thickness wounds in athymic mice were tested. In
      vitro evaluation of freeze-dried collagen skin substitutes (FCSS) and electrospun
      collagen skin substitutes (ECSS) revealed no significant differences in cell
      proliferation, surface hydration, or cellular organization between the ECSS and
      FCSS groups. Both groups exhibited excellent stratification with a continuous
      layer of basal keratinocytes present at the dermal-epidermal junction. After
      grafting to full thickness wounds in athymic mice, both skin substitutes had high
      rates of engraftment: 87.5% in the FCSS group and 100% in the ECSS group.
      Histological evaluation of wounds revealed that bovine collagen persisted in the
      wound at week 8 in the FCSS group while no bovine collagen was seen in the ECSS
      group. At 8 weeks post-grafting, the ECSS grafts were 61.3+/-7.9% original graft
      area whereas the FCSS grafts were 39.2+/-8.8% original area (p<0.01). These
      results indicate that ES scaffolds can be used to fabricate skin substitutes with
      optimal cellular organization and can potentially reduce wound contraction
      compared to FD scaffolds. These advantages may lead to reduced morbidity in
      patients treated with skin substitutes fabricated from ES collagen.

PMID- 18054075
TI  - Impaired placentation in fetal alcohol syndrome.
AB  - Intrauterine growth restriction (IUGR) is one of the key features of fetal
      alcohol syndrome (FAS), and IUGR can be mediated by impaired placentation.
      Insulin-like growth factors (IGF) regulate placentation due to stimulatory
      effects on extravillous trophoblasts, which are highly motile and invasive.
      Previous studies demonstrated that extravillous trophoblasts express high levels
      of aspartyl-(asparaginyl) beta-hydroxylase (AAH), a gene that is regulated by IGF
      and has a critical role in cell motility and invasion. The present study examines
      the hypothesis that ethanol impaired placentation is associated with inhibition
      of AAH expression in trophoblasts. Pregnant Long Evans rats were fed isocaloric
      liquid diets containing 0% or 37% ethanol by caloric content. Placentas harvested
      on gestation day 16 were used for histopathological, mRNA, and protein studies to
      examine AAH expression in relation to the integrity of placentation and ethanol
      exposure. Chronic ethanol feeding prevented or impaired the physiological
      conversion of uterine vessels required for expansion of maternal circulation into
      placenta, a crucial process for adequate placentation. Real-time quantitative RT
      PCR analysis demonstrated significant reductions in IRS-1, IRS-2, and significant
      increases in IGF-II and IGF-II receptor mRNA levels in ethanol-exposed placentas.
      These abnormalities were associated with significantly reduced levels of AAH
      expression in trophoblastic cells, particularly within the mesometrial triangle
      (deep placental bed) as demonstrated by real time quantitative RT-PCR, Western
      blot analysis, ELISA, and immunohistochemical staining. Ethanol-impaired
      placentation is associated with inhibition of AAH expression in trophoblasts.
      This effect of chronic gestational exposure to ethanol may contribute to IUGR in
      FAS.

PMID- 18054076
TI  - Modeling trophoblast differentiation using equine chorionic girdle vesicles.
AB  - The chorionic girdle of the equine conceptus is comprised of specialized
      trophoblast cells which, at day 36-38 of equine pregnancy, gain an invasive
      phenotype and invade the endometrium to form endometrial cups. Studies of equine
      endometrial cups remain difficult to perform because of the invasive techniques
      required to obtain cup tissue and because sampling requires termination of the
      pregnancy. In this study we developed a system to model trophoblast
      differentiation and trophoblast-immune interactions in vitro and in vivo. We
      utilized a method of culturing chorionic girdle pieces in serum-free medium to
      promote spontaneous formation of vesicle structures enriched for terminally
      differentiated binucleate cells that secreted equine chorionic gonadotrophin
      (eCG). Immunohistochemical staining and scanning electron microscopy showed that
      the cells of the vesicles closely resembled the outer layers of chorionic girdle
      immediately prior to invasion. Chorionic girdle vesicles were harvested after 72h
      in culture and ectopically transplanted via injection into the vulvar mucosa of
      recipient mares. At 7, 14, 21 and 28days after transplantation, biopsies of the
      injection sites were obtained. Immunohistochemical labeling of cryostat sections
      of the biopsies with a panel of monoclonal antibodies to horse trophoblast
      molecules demonstrated survival, differentiation, and presence of trophoblast
      cells for at least 21days. Serial sections of the biopsies labeled with
      antibodies to the equine lymphocyte surface markers CD4 and CD8, together with
      lymphocyte microcytotoxicity assays, revealed that the recipients mounted both
      cellular and humoral antibody immune responses to the transplanted trophoblast
      cells. This new method for culturing equine chorionic girdle trophoblast cells,
      and for transplanting trophoblast vesicles to ectopic sites, should allow
      identification of key aspects of trophoblast differentiation and the interactions
      that occur between invasive trophoblast and the maternal immune system.

PMID- 18054077
TI  - Store-operated Ca2+ entry in astrocytes: different spatial arrangement of
      endoplasmic reticulum explains functional diversity in vitro and in situ.
AB  - Ca(2+) signaling is the astrocyte form of excitability and the endoplasmic
      reticulum (ER) plays an important role as an intracellular Ca(2+) store. Since
      the subcellular distribution of the ER influences Ca(2+) signaling, we compared
      the arrangement of ER in astrocytes of hippocampus tissue and astrocytes in cell
      culture by electron microscopy. While the ER was usually located in close
      apposition to the plasma membrane in astrocytes in situ, the ER in cultured
      astrocytes was close to the nuclear membrane. Activation of metabotropic
      receptors linked to release of Ca(2+) from ER stores triggered distinct responses
      in cultured and in situ astrocytes. In culture, Ca(2+) signals were commonly
      first recorded close to the nucleus and with a delay at peripheral regions of the
      cells. Store-operated Ca(2+) entry (SOC) as a route to refill the Ca(2+) stores
      could be easily identified in cultured astrocytes as the Zn(2+)-sensitive
      component of the Ca(2+) signal. In contrast, such a Zn(2+)-sensitive component
      was not recorded in astrocytes from hippocampal slices despite of evidence for
      SOC. Our data indicate that both, astrocytes in situ and in vitro express SOC
      necessary to refill stores, but that a SOC-related signal is not recorded in the
      cytoplasm of astrocytes in situ since the stores are close to the plasma membrane
      and the refill does not affect cytoplasmic Ca(2+) levels.

PMID- 18054078
TI  - Toxicity reference values for mink exposed to 2,3,7,8-tetrachlodibenzo-p-dioxin
      (TCDD) equivalents (TEQs).
AB  - Dietary and tissue residue-based toxicity reference values (TRVs) were derived
      for mink from the published results of studies in which mink were exposed to
      polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls
      (PCBs), or related compounds. Because the primary mechanism of toxic action at
      the least concentration for these compounds is related to activation of the aryl
      hydrocarbon receptor (AhR), TRVs were described on the basis of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQ). Each published study was
      critically reviewed for its usefulness in deriving a TRV based on the following
      criteria: (1) close relatedness of the test species to the wildlife receptor of
      concern (only mink studies were reviewed in this paper); (2) chronic duration of
      exposure which included sensitive life stages to evaluate potential developmental
      and reproductive effects; (3) measurement of ecologically relevant endpoints; (4)
      availability of congener-specific data to calculate TEQ concentrations; and (5)
      minimal impact of co-contaminants. Dietary TRVs for mink exposed to TEQ ranged
      from 12.1 to 56.6 ng TEQ/kg feed (wet weight) for the no observable adverse
      effect level (NOAEL) and from 50.4 to 242 ng TEQ/kg feed (wet weight) for the
      lowest observable adverse effect level (LOAEL). TRVs based on tissue residue
      concentrations ranged from 50.2 to 77.8 ng TEQ/kg liver (wet weight) for the no
      observable adverse effect concentration (NOAEC) and the value was 189 ng TEQ/kg
      liver (wet weight) for the lowest observable adverse effect concentration
      (LOAEC). Selection of a TRV should be based on studies of compounds that are most
      similar to those at a site of interest. In particular, it was determined that the
      effects of PCDFs could not be accurately predicted from the use of TEQ-based TRVs
      developed from studies of PCDDs or PCBs. Risk assessors should be aware that
      exceedance of these TRVs would not necessarily be expected to lead to
      ecologically relevant adverse effects because of the inherently conservative
      assumptions made in the TRV derivation process.

PMID- 18054079
TI  - Monitoring concentrations of persistent organic pollutants in the general
      population: the international experience.
AB  - Assessing the adverse effects on human health of persistent organic pollutants
      (POPs) and the impact of policies aiming to reduce human exposure to POPs
      warrants monitoring body concentrations of POPs in representative samples of
      subjects. While numerous ad hoc studies are being conducted to understand POPs
      effects, only a few countries are conducting nationwide surveillance programs of
      human concentrations of POPs, and even less countries do so in representative
      samples of the general population. We tried to identify all studies worldwide
      that analyzed the distribution of concentrations of POPs in a representative
      sample of the general population, and we synthesized the studies' main
      characteristics, as design, population, and chemicals analyzed. The most
      comprehensive studies are the National Reports on Human Exposure to Environmental
      Chemicals (USA), the German Environmental Survey, and the Arctic Monitoring and
      Assessment Programme. Population-wide studies exist as well in New Zealand,
      Australia, Japan, Flanders (Belgium) and the Canary Islands (Spain). Most such
      studies are linked with health surveys, which is a highly-relevant additional
      strength. Only the German and Flemish studies analyzed POPs by educational level,
      while studies in the USA offer results by ethnic group. The full distribution of
      POPs concentrations is unknown in many countries. Knowledge gaps include also the
      interplay of age, gender, period and cohort effects on the prevalence of
      exposures observed by cross-sectional surveys. Local and global efforts to
      minimize POPs contamination, like the Stockholm convention, warrant nationwide
      monitoring of concentrations of POPs in representative samples of the general
      population. Results of this review show how such studies may be developed and
      used.

PMID- 18054080
TI  - WITHDRAWN: Arsenic contamination of vegetables grown in arsenic contaminated
      areas of Bangladesh and estimation of arsenic intake from vegetables by the local
      population.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The publisher
      apologizes for any inconvenience this may cause.

PMID- 18054081
TI  - Cobalt and secondary poisoning in the terrestrial food chain: data review and
      research gaps to support risk assessment.
AB  - Cobalt is a naturally occurring element found in rocks, soil, water, plants, and
      animals and has diverse industrial importance. It is cycled in surface
      environments through many natural processes (e.g. volcanic eruptions, weathering)
      and can be introduced through numerous anthropogenic activities (e.g. burning of
      coal or oil, or the production of cobalt alloys). The environmental behaviour of
      cobalt in terrestrial environment is relatively poorly studied and in particular
      where Co is used in industrial processes, the baseline information to support
      wider and long-term environmental impacts is widely dispersed. To support the
      adoption of new EU regulations on the risk assessment of chemicals, we review
      here the various aspects of the environmental chemistry, fate and transport of Co
      across environmental interfaces and discuss the toxicology and potential for bio
      magnification and food chain accumulation. The soil-to-plant transfer of Co
      appears to be viable route to expose lower trophic levels to biologically
      significant concentrations and Co is potentially accumulated in biomass and top
      soil. Evidence for further accumulation through soil-invertebrate transfer and to
      higher trophic levels is suggested by some studies but this is obscured by the
      relatively high variability of published transfer data. This variation is not due
      to one particular aspect of the transfer of Co in terrestrial environments.
      Influences are from the variability of geological sources within soil systems;
      the sensitivity of Co mobility to environmental factors (e.g. pH) and the variety
      of life strategies for metal elimination/use within biological species. Toxic
      effects of Co have been suggested for some soil-plant animal studies however,
      uncertainty in the extrapolation from laboratory to field is a major limitation.

PMID- 18054082
TI  - An efficient algorithm for continuous time cross correlogram of spike trains.
AB  - We propose an efficient algorithm to compute the smoothed correlogram for the
      detection of temporal relationship between two spike trains. Unlike the
      conventional histogram-based correlogram estimations, the proposed algorithm
      operates on continuous time and does not bin either the spike train nor the
      correlogram. Hence it can be more precise in detecting the effective delay
      between two recording sites. Moreover, it can take advantage of the higher
      temporal resolution of the spike times provided by the current recording methods.
      The Laplacian kernel for smoothing enables efficient computation of the
      algorithm. We also provide the basic statistics of the estimator and a guideline
      for choosing the kernel size. This new technique is demonstrated by estimating
      the effective delays in a neuronal network from synthetic data and recordings of
      dissociated cortical tissue.

PMID- 18054083
TI  - Development of a canine nociceptive thermal escape model.
AB  - Acute nociceptive models which have been validated for large animal species are
      limited, yet nociceptive assessment in non-rodent species is important in
      analgesic drug development where larger animals may be necessary because of the
      technical requirements of the study. Here we report development and validation of
      a canine hind paw thermal escape model and the effect of analgesics on withdrawal
      latencies. Individual focused projection bulbs were used as left and right
      voltage-adjusted thermal stimuli placed below a glass plate in a specifically
      designed canine holding apparatus. After acclimation, dogs were lightly
      restrained in a fabric sling while standing on the glass plate. The anterior
      center of the metatarsal pad of the left and right hind paw was positioned on the
      glass over each light, and duration of stimulation tolerance timed. For every
      trial, the escape latency from lamp actuation to paw withdrawal was recorded
      twice for each hind paw. The mean population baseline withdrawal latency of 9.3+/
      1.7s (mean+/-S.D., n=12 dogs) was shown to be repeatable between paws, within and
      between individual animals, and between test days. This latency corresponded to a
      glass surface temperature of 49.5 degrees C. A cut-off time of 20s (corresponding
      to a glass surface temperature of 56.5 degrees C) was set to prevent tissue
      damage. Intravenous administration (mg/kg) of morphine (1.0), hydromorphone
      (0.2), butorphanol (0.4), fentanyl (0.01), and dexmedetomidine (0.01)
      significantly (p<0.05) increased withdrawal latency from baseline within 15-30
      min of administration while buprenorphine (0.03) produced a delayed, modest but
      significant latency increase. Rank order of opioid analgesic duration was
      morphine=hydromorphone>butorphanol>bupenorphine>fentanyl=saline. A dose-effect
      curve for hydromorphone was generated and corresponded to previously described
      dose-effect relationships in other species. The non-analgesic tranquilizer
      acepromazine (0.1mg/kg) produced mild sedation, but no significant increase in
      latency from that of saline. The model yielded a clear distinction between
      analgesia and sedation for all agents tested. These studies provide validation of
      a canine thermal escape model and have demonstrated the efficacy of clinically
      relevant doses of analgesics in elevating escape latencies. This model will
      facilitate quantification of the effects of parenterally and neuraxially
      administered analgesics in dogs.

PMID- 18054084
TI  - Bootstrap significance of low SNR evoked response.
AB  - In order to obtain adequate signal to noise ratio (SNR), stimulus-evoked brain
      signals are averaged over a large number of trials. However, in certain
      applications, e.g. fetal magnetoencephalography (MEG), this approach fails due to
      underlying conditions (inherently small signals, non-stationary/poorly
      characterized signals, or limited number of trials). The resulting low SNR makes
      it difficult to reliably identify a response by visual examination of the
      averaged time course, even after pre-processing to attenuate interference. The
      purpose of this work was to devise an intuitive statistical significance test for
      low SNR situations, based on non-parametric bootstrap resampling. We compared a
      two-parameter measure of p-value and statistical power with a bootstrap equal
      means test and a traditional rank test using fetal MEG data collected with a
      light flash stimulus. We found that the two-parameter measure generally agreed
      with established measures, while p-value alone was overly optimistic. In an
      extension of our approach, we compared methods to estimate the background noise.
      A method based on surrogate averages resulted in the most robust estimate. In
      summary we have developed a flexible and intuitively satisfying bootstrap-based
      significance measure incorporating appropriate noise estimation.

PMID- 18054085
TI  - Molecular cloning and expression of a larval immunogenic protein from the cattle
      tick Boophilus annulatus.
AB  - A full-length cDNA of an immunogenic protein was cloned from a cDNA library of
      the local Egyptian cattle tick Boophilus annulatus. Antibodies raised against B.
      annulatus larval proteins were used to screen a cDNA expression library. A 936bp
      cloned fragment was sequenced and showed an open reading frame of 516bp encoding
      a protein of 171 amino acids. Comparison of the deduced amino acid sequence with
      protein data bank revealed that the sequence is related to a sequence isolated
      from the hard tick Haemaphysalis qinghaiensis (Hq05). Southern blot analysis of
      B. annulatus genomic DNA showed that the cloned cDNA hybridized to double bands
      per restriction digest, suggesting that the cloned cDNA is a double copy gene.
      Amino acid analysis of the cloned gene revealed the presence of two casein kinase
      II phosphorylation sites in the N-terminal domain suggesting that this molecule
      may be involved in the signal transduction or gene expression pathways. RT-PCR
      and northern blotting revealed the presence of two isoforms of the Ba05 gene in
      salivary glands and in the 3-day-old eggs. The cloned gene without the signal
      peptide, was expressed in Escherichia coli under T7 promotor of pET-30b vector,
      and purified under denaturation conditions. The purified protein appeared as a
      single band on 12% SDS-PAGE with a molecular weight around 22.8kDa including the
      histidine tag of the vector. Antibodies raised against the purified molecule were
      used to detect the B. annulatus homologue to the Hq05 gene in whole tick, larvae
      and gut protein extracts. Immunoblotting revealed the presence of this molecule
      Ba05 only in whole tick and larval protein extracts and not in the gut protein
      extract. Using the same antibodies, homologues to the Ba05 gene were detected in
      other tick species as Hyalomma dromedarii and Rhipicephalus sp. but not in
      Ornithodoros moubata.

PMID- 18054087
TI  - Intracellular mediators of CXCR4-dependent signaling in T cells.
AB  - The signaling pathways induced in T lymphocytes by CXCR4-CXCL12 interaction,
      which lead to the cytoskeletal macro-rearrangements observable in migrating
      cells, are as yet largely uncharacterized. The aim of this review is to briefly
      summarize the current knowledge of the signaling machinery which controls the
      process of chemotaxis in CXCL12-stimulated T lymphocytes.

PMID- 18054088
TI  - Published studies reporting the efficacy of soluble CD83 in vitro as well as in
      vivo.

PMID- 18054089
TI  - Heteroduplex mobility assay and single-stranded conformation polymorphism
      analysis as methodologies for detecting variants of human erythroviruses.
AB  - Variant samples from the three genotypes of erythroviruses have already been
      detected using sequencing as methodology for analysis. This study aimed to
      investigate the efficacy of single-stranded conformation polymorphism (SSCP)
      analysis and heteroduplex mobility assay (HMA) as methodologies to detect human
      erythrovirus variants, using their VP1 unique region sequences. Clinical samples
      and plasmids of PVBAUA, A6, LaLi, V9Gh3051, and D91.1 erythrovirus variants as
      prototypes of the three genotypes were used. SSCP analysis was able to
      distinguish all divergences among the plasmids, including the two mutation points
      between LaLi and A6 plasmids that led to distinct electrophoresis mobility
      patterns. Although HMA analysis was unabled to detect two mutation points between
      LaLi and A6, it enabled the differentiation among all other plasmids that
      revealed specific electrophoresis patterns, with high-enough sensibility to
      detect 1.5% nucleotide substitutions. When 57 clinical samples were analyzed, 33
      of them presented an identical pattern to PVBAUA by HMA and SSCP analyses, two of
      them were sequenced and presented an identical sequence in relation to PVBAUA.
      Another pattern was found for 21 samples. Among these, two samples were
      sequenced, revealing one mutation point in relation to PVBAUA, while each one of
      the three remaining samples presented a distinct pattern, showing two or three
      mutations in relation to PVBAUA by sequencing. HMA and SSCP analyses were
      suggested as methodologies suited for detecting genetic mutations of human
      erythroviruses in developing countries because of their practicability and minor
      costs for reagents and equipment.

PMID- 18054090
TI  - Construction, properties, and potential application of infectious plasmids
      containing Semliki Forest virus full-length cDNA with an inserted intron.
AB  - Semliki Forest virus (SFV, genus Alphavirus) has a broad host range, high
      efficiency of viral protein expression, and the ability to stimulate an immune
      response. These properties have made SFV an attractive tool for development of
      expression vectors, and plasmid clones containing cDNA of the SFV genome often
      are used. However, instability of these plasmids resulting from cryptic
      expression of SFV envelope proteins in Escherichia coli represents a problem both
      for the development of SFV-based vectors and for SFV research. In this study, an
      infectious plasmid of SFV, pCMV-SFV4, was constructed; its toxic effect was
      eliminated by intron insertion in the capsid protein encoding region. When
      transfected into mammalian cells, the plasmid clone was highly infectious and
      produced virus with properties identical to those of wild-type SFV. The inserted
      intron was efficiently and properly removed from the RNA genome of SFV.
      Therefore, this novel and stabilized infectious SFV plasmid represents a superior
      tool for basic studies of SFV as well as for biotechnological applications.

PMID- 18054091
TI  - Development of a rapid immunochromatographic test for noroviruses genogroups I
      and II.
AB  - Norovirus (NoV) is known to cause acute gastroenteritis in children worldwide.
      Although reverse transcription-PCR (RT-PCR) method is considered to be the "gold
      standard" for diagnosis of this viral infection, it requires skillful personnel
      and well-equipped laboratory. In this study, a rapid and easily performable
      diagnostic kit was developed using immunochromatographic method with rabbit
      polyclonal antibodies raised against recombinant virus-like particles (rVLPs) of
      most prevalent genotypes, genogroup II genotypes 3 and 4. This kit was evaluated
      for reactivity to rVLPs and detection of natural viruses in stool samples
      collected from children with diarrhea in comparison to the results obtained by RT
      PCR. In the prospective assessment, the kit showed agreement rate of 84.1%,
      sensitivity of 69.8% and specificity of 93.7%. Genotyping of the RT-PCR positive
      samples by sequence analysis revealed that some heterogeneous genotypes were also
      detected while some in homogeneous genotypes occasionally showed false negative
      records resulting in lower sensitivity. No cross-reactivity with other common
      viral pathogens was observed. Taken together with the result of the detection
      limit of viral load as small as approximately 10(6-7)copies/g of stool, the
      current immunochromatography test is justified for screening for NoV infection
      with simple laboratory support.

PMID- 18054086
TI  - Gene expression profiling of porcine peripheral blood leukocytes after infection
      with Actinobacillus pleuropneumoniae.
AB  - The gene expression profile of peripheral blood leukocytes (PBL) from extreme
      performing pigs after infection with Actinobacillus pleuropneumoniae was analysed
      using a custom complementary DNA (cDNA) microarray and quantitative reverse
      transcription-PCR (qRT-PCR). Four high performing animals with low disease-score
      (HP), three low performing animals with high disease-score (LP) and one medium
      performing animal with medium disease-score (MP) were selected for microarray
      profiling. PBL RNA from these eight pigs collected before and at 24h after APP
      infection, was examined. The study identified 92 genes that were up-regulated and
      four genes that were down-regulated in PBL RNA from HP pigs compared to LP pigs.
      The majority of differentially expressed (DE) genes were identified by virtue of
      their elevated expression in the HP animals at 24h post-infection. A large number
      of annotated DE genes are involved in innate immune response pathways. The gene
      expression profile of 10 DE candidate genes was further explored across the
      entire pig population in the same infection trial using qRT-PCR. Considerable
      animal-to-animal variation in PBL gene expression was observed, especially in the
      LP group. The qRT-PCR analysis suggested that only one true LP pig might be
      present in this study, which contributes significantly to the differential
      expression profile of the selected genes in HP animals following APP infection.
      This study has therefore identified a set of genes which could serve as molecular
      indicators for an effective immune response to APP in pigs and which could also
      serve as source for gene marker development in molecular genetics studies of
      heritable immune traits.

PMID- 18054092
TI  - International research networks in viral structural proteomics: again, lessons
      from SARS.
AB  - Emerging and re-emerging pathogens and bioterror threats require an organized and
      coherent response from the worldwide research community to maximize available
      resources and competencies with the primary goals to understand the pathogen and
      enable intervention. In 2001, the Structural Proteomics In Europe (SPINE) project
      prototyped the pan-viral structural genomic approach, and the Severe Acute
      Respiratory Syndrome (SARS) outbreak in 2003 accelerated the concept of
      structural characterization of all proteins from a viral proteome and the
      interaction with their host partners. Following that approach, in 2004 the center
      for Functional and Structural Proteomics for SARS-CoV related proteins was
      initiated as part of the US NIH NIAID proteomics resource centers. Across
      worldwide efforts in Asia, Europe and America, the international research teams
      working on SARS-CoV have now determined experimental structural information for
      45% of the SARS-CoV proteins and 53% of all its soluble proteins. This data is
      fully available to the scientific community and is providing an unprecedented
      level of insight to this class of RNA viruses. The efforts and results by the
      international scientific community to the SARS outbreak are serving as an example
      and roadmap of a rapid response using modern research methods.

PMID- 18054093
TI  - Plasmodium falciparum signal peptidase is regulated by phosphorylation and
      required for intra-erythrocytic growth.
AB  - The human malaria parasite Plasmodium falciparum exports a variety of its
      proteins through its endoplasmic reticulum (ER) based secretory pathway in order
      to survive in the host erythrocyte. Signal peptidases are membrane-bound
      endopeptidases and have an important role in the transport and maturation of
      these parasite proteins. Prokaryotic signal peptidases are indispensable enzymes
      required for the removal of N-terminal signal peptide from the secretory
      proteins. Eukaryotic signal peptidases exist as multimeric protein complex in the
      ER and the catalytic subunit of this complex catalyzes removal of the N-terminal
      signal peptide from preproteins. All the signal peptidases contain five regions
      of high-sequence similarity referred to as boxes A-E. Here we report
      characterization of the catalytic subunit of signal peptidase complex (SPC) from
      P. falciparum. This protein designated as PfSP21 shows homology with the similar
      subunit from other sources and contains all the conserved boxes A-E. PfSP21 is
      able to cleave the peptide substrate containing the signal peptidase cleavage
      site. PfSP21 is phosphorylated by protein kinase C and its enzyme activity was
      upregulated after this phosphorylation. Immunofluorescence assay studies revealed
      that PfSP21 is localized in the ER of P. falciparum. PfSP21 dsRNA specifically
      inhibits the growth of P. falciparum in culture and this inhibition is most
      likely due to the decrease in the amount of endogenous PfSP21 protein. These
      studies demonstrate the characterization of a functional subunit of SPC from P.
      falciparum and should make an important contribution in our better understanding
      of the complex process of protein translocation in the parasite.

PMID- 18054094
TI  - Poly(ADP-ribose) activation in circulating cells in human myocardial infarction.

PMID- 18054095
TI  - Use of a high thoracic epidural analgesia for treatment of end-stage congestive
      heart failure secondary to coronary artery disease: effect of HTEA on CHF.
AB  - We present the case of a patient with end-stage congestive heart failure (NYHA
      class IV) secondary to ischemic cardiomyopathy despite maximally medical therapy,
      who needed to have a coronary artery bypass graft (CABG) surgery but whose risk
      was considered too high due to his deteriorating cardiac function. Cardiac
      sympathetic blockade by high thoracic epidural analgesia (HTEA) was added to
      stabilize the patient's critical condition before surgery. HTEA was performed at
      the T1 through T5 levels with a catheter placed percutaneously and then lidocaine
      (0.5%, 3-5 ml) was given as intermittent injections through the epidural
      catheter. The combination of HTEA treatment resulted in a rapid hemodynamic and
      clinical improvement and no serious catheter-related complications occurred. This
      case suggests that HTEA seems to be an effective and safe adjuvant therapeutics
      and can be used as a short-term bridge to CABG or cardiac transplantation in
      patients with end-stage congestive heart failure.

PMID- 18054096
TI  - CE-SSCP and CE-FLA, simple and high-throughput alternatives for fungal diversity
      studies.
AB  - Fungal communities are key components of soil, but the study of their ecological
      significance is limited by a lack of appropriated methods. For instance, the
      assessment of fungi occurrence and spatio-temporal variation in soil requires the
      analysis of a large number of samples. The molecular signature methods provide a
      useful tool to monitor these microbial communities and can be easily adapted to
      capillary electrophoresis (CE) allowing high-throughput studies. Here we assess
      the suitability of CE-FLA (Fragment Length Polymorphism, denaturing conditions)
      and CE-SSCP (Single-Stranded Conformation Polymorphism, native conditions)
      applied to environmental studies since they require a short molecular marker and
      no post-PCR treatments. We amplified the ITS1 region from 22 fungal strains
      isolated from an alpine ecosystem and from total genomic DNA of alpine and
      infiltration basin soils. The CE-FLA and CE-SSCP separated 17 and 15 peaks
      respectively from a mixture of 19 strains. For the alpine soil-metagenomic DNA,
      the FLA displayed more peaks than the SSCP and the converse result was found for
      infiltration basin sediments. We concluded that CE-FLA and CE-SSCP of ITS1 region
      provided complementary information. In order to improve CE-SSCP sensitivity, we
      tested its resolution according to migration temperature and found 32 degrees C
      to be optimal. Because of their simplicity, quickness and reproducibility, we
      found that these two methods were promising for high-throughput studies of soil
      fungal communities.

PMID- 18054097
TI  - An enhanced miniaturized assay for antimicrobial prospecting.
AB  - Bioprospecting for novel antimicrobials increasingly relies on extremely small
      samples unsuitable for conventional bulk extraction and assay. We developed a
      microtitre plate assay for minimal amounts of test materials which is rapid,
      extremely sensitive, allows time-course analysis and reduces false negatives.
      Developed for the analyses of antimicrobial sensitivity and resistance, the
      technique is appropriate for assays where source materials are scarce.

PMID- 18054098
TI  - Rapid detection of ESBL-producing Klebsiella pneumoniae in blood cultures by
      fluorescent in-situ hybridization.
AB  - Multi-resistant Enterobacteriaceae pose a serious threat of hospital acquired
      infections and their rapid identification is important for better clinical
      outcome. This study describes the rapid identification of extended-spectrum beta
      lactamase-producing Klebsiella pneumoniae of the sulphydryl variable-type by
      fluorescent in-situ hybridization. The method which rapidly identifies the target
      genes within 1 h could be a potentially rapid bacterial diagnostic tool.

PMID- 18054099
TI  - Enumeration of airborne bacteria and fungi using solid phase cytometry.
AB  - Conventional methods for the enumeration of airborne micro-organisms are
      inaccurate and time-consuming, hence the interest in novel approaches is
      increasing. In the present study, the use of solid phase cytometry (SPC) was
      evaluated for the enumeration of airborne micro-organisms. A 4 h SPC procedure
      based on viability staining was applied to samples from 50 locations and compared
      with an optimised culture-based method. Plate counts after air sampling were
      repeatable but strongly dependent on sampling volume. Samples with low or high
      microbial load were difficult to analyse using the culture-based method, unlike
      with SPC. Results show that SPC can be considered superior to the culture-based
      method because of its much higher dynamic range, its speed and its ability to
      enumerate not only culturable but all viable micro-organisms.

PMID- 18054100
TI  - Use of activated carbon coated with bentonite for increasing the sensitivity of
      pcr detection of Escherichia coli O157:H7 in Canadian oyster (Crassostrea gigas)
      tissue.
AB  - A novel method for directly increasing the recovery of Escherichia coli O157:H7
      and efficiently eliminating PCR inhibitors in oyster tissue without preenrichment
      was developed with the use of activated carbon coated with bentonite. The
      recovery of E. coli O157:H7 was significantly affected by the amount of bentonite
      used to coat the activated charcoal and the pH value of sample preparations. When
      4.2 g of activated carbon were coated with 0.4 g of bentonite and seeded oyster
      samples were adjusted to a pH of 5.0, a high recovery of E. coli O157:H7 (91.6+/
      4.4%) was obtained. Activated carbon, coated with bentonite, allowed the PCR
      detection of 1.5 x 10(2) CFU/g of oyster tissue which was equivalent to 30
      genomic targets per PCR reaction. Without the use of activated carbon coated with
      bentonite, the minimum level of detection was 1.5 x 10(5) CFU/g of oyster tissue,
      which is equivalent to 3.0 x 10(4) genomic targets per PCR reaction. Three
      commercial DNA purification systems were used for comparison. The limit of
      detection with the Wizard DNA Clean-Up System and the Chelex(R)100 Resin was 1.5
      x 10(3) CFU/g of oyster tissue which was equivalent to 3.0 x 10(2) CFU/PCR
      reaction. The QIAamp DNA Mini Kit resulted in a detection limit of 5 x 10(2)
      CFU/g of oyster tissue which was equivalent to 5 x 10(2) genomic targets per PCR
      reaction. The use of activated carbon coated with bentonite is an inexpensive
      method for removal of PCR inhibitors from tissue samples prior to the release of
      DNA from target cells resulting in relatively low numbers of target cells
      detected without enrichment.

PMID- 18054101
TI  - HDR prostate monotherapy: dosimetric effects of implant deformation due to
      posture change between TRUS- and CT-imaging.
AB  - HDR monotherapy for prostate cancer consists of four fractions. The first
      fraction is delivered with online TRUS-based treatment planning. For the last
      three fractions the treatment plan is based on a CT-scan acquired in between
      fractions 1 and 2. The patient position (high lithotomy, rectal US probe) during
      TRUS-guided catheter implantation and first fraction differs from the patient
      position in the CT-scan and the remaining three fractions (lowered legs, no TRUS
      probe). This study describes the effect of posture changes on dose distributions
      when a plan designed for the TRUS anatomy is applied to the CT-scan anatomy. The
      aim is to quantify dosimetrical errors that would result from skipping the use of
      a planning CT-scan, and rely for all fractions on the TRUS plan. Such a procedure
      would substantially reduce the involved workload, and would increase patient
      comfort. For three prostate cancer patients, images were acquired during TRUS
      guided catheter implantation. Furthermore, a CT-scan (no US probe in rectum,
      different position of legs) was acquired and matched with the TRUS set. On both
      TRUS and CT, prostate, urethra and rectum were delineated and all catheters were
      traced. For each patient, an optimized treatment plan was designed using TRUS
      images and contours. Catheters with obtained dwell positions of the TRUS plan
      were transferred individually to the catheter positions in the CT. Changes in
      dose distribution due to relocation of catheters were evaluated using DVHs. For
      all patients the dose distributions changed significantly due to rearrangement of
      the catheters, having most impact on the urethra (maximum observed change: 32%
      volume receiving > or = 120% of the prescribed dose) and a reduction of PTV
      coverage (6-28%). Implant deformation when changing from TRUS patient set-up to
      CT set-up affected negatively the quality of optimized treatment plans. Inclusion
      of more patients in this study was planned, but because of the observed strong
      negative effects it is already concluded that the TRUS plan cannot be used for
      the last three fractions with a deviating patient set-up.

PMID- 18054102
TI  - The next step in patient-specific QA: 3D dose verification of conformal and
      intensity-modulated RT based on EPID dosimetry and Monte Carlo dose calculations.
AB  - BACKGROUND AND PURPOSE: A method was evaluated to reconstruct the 3D dose
      distribution in patients using their planning CT-scan in combination with a Monte
      Carlo calculation, and the energy fluence of the actual treatment beams measured
      pre-treatment with an EPID without the patient or a phantom in the beam.
      MATERIALS AND METHODS: Nine plans of lung cancer patients treated with a 3D
      conformal technique, calculated using a simple convolution algorithm (CA), as
      well as five IMRT treatments of head-and-neck cancer patients, calculated with a
      more advanced superposition algorithm (SA), were verified. Differences between
      planned and reconstructed dose distributions were quantified in terms of DVH
      parameters. RESULTS: For the lung cancer group, differences between the
      reconstructed mean PTV dose and the values calculated with the TPS were 5.0+/
      4.2% (1SD) and -1.4+/-1.5% for the CA and SA algorithm, respectively. No large
      differences in the lung and spinal cord DVH parameters were found. For the IMRT
      treatments, the average dose differences in the PTV were generally below 3%. The
      reconstructed mean parotid gland dose was 3.2+/-1.2% lower, while the maximum
      spinal cord dose was on average 3.1+/-1.9% higher. CONCLUSIONS: EPID dosimetry
      combined with 3D dose reconstruction is a useful procedure for patient-specific
      QA of complex treatments. DVH parameters can be used to interpret the dose
      distribution delivered to the patient in the same way as during standard
      treatment plan evaluation.

PMID- 18054103
TI  - Evaluation of margining algorithms in commercial treatment planning systems.
AB  - INTRODUCTION: During commissioning of the Pinnacle (Philips) treatment planning
      system (TPS) the margining algorithm was investigated and was found to produce
      larger PTVs than Plato (Nucletron) for identical GTVs. Subsequent comparison of
      PTV volumes resulting from the QA outlining exercise for the CHHIP (Conventional
      or Hypofractionated High Dose IMRT for Prostate Ca.) trial confirmed that there
      were differences in TPS's margining algorithms. Margining and the clinical impact
      of the different PTVs in seven different planning and virtual simulation systems
      (Pinnacle, Plato, Prosoma (MedCom), Eclipse (7.3 and 7.5) (Varian), MasterPlan
      (Nucletron), Xio (CMS) and Advantage Windows (AW) (GE)) is investigated, and a
      simple test for 3D margining consistency is proposed. METHODS: Using each TPS,
      two different sets of prostate GTVs on 2.5mm and 5mm slices were margined
      according to the CHHIP protocol to produce PTV3 (prostate+5 mm/0 mm post), PTV2
      (PTV3+5 mm) and PTV1 (prostate and seminal vesicles+10 mm). GTVs and PTVs were
      imported into Pinnacle for volume calculation. DVHs for 5mm slice plans, created
      using the smallest PTVs, were recalculated on the largest PTV dataset and vice
      versa. Since adding a margin of 50 mm to a structure should give the same result
      as adding five margins of 10 mm, this was tested for each TPS (consistency test)
      using an octahedron as the GTV and CT datasets with 2.5 mm and 5 mm slices.
      RESULTS: The CHHIP PTV3 and PTV1 volumes had a standard deviation, across the
      seven systems, of 5% and PTV2 (margined twice) 9%, on the 5 mm slices. For 2.5 mm
      slices the standard deviations were 4% and 6%. The ratio of the Pinnacle and the
      Eclipse 7.3 PTV2 volumes was 1.25. Rectal doses were significantly increased when
      encompassing Pinnacle PTVs (V(50)=42.8%), compared to Eclipse 7.3 PTVs
      (V(50)=36.4%). Conversely, fields that adequately treated an Eclipse 7.3 PTV2
      were inadequate for a Pinnacle PTV2. AW and Plato PTV volumes were the most
      consistent (0.3%) and (-0.4%). However, the 1x50mm margin in Pinnacle produced a
      15.9% larger volume than 5 x 10 mm margins, while for Eclipse 7.3 the single
      margined volume was 14.3% smaller. These inconsistencies were reduced to
      approximately 5% by adjusting the superior/inferior margins. CONCLUSIONS:
      Accurate margin algorithms are necessary to ensure that volume expansion does not
      add extra uncertainty to the radiotherapy planning process. We have found
      significant differences in the 3D margining algorithms of TPSs, devised a simple
      test to predict inconsistency and suggested corrective action to minimise the
      variation.

PMID- 18054104
TI  - Neuroprotective effects of genistein on dopaminergic neurons in the mice model of
      Parkinson's disease.
AB  - Emerging evidence suggests beneficial effects of estrogen and estrogen-like
      chemicals on neurodegenerative diseases, especially Parkinson's disease (PD).
      Genistein, an isoflavone naturally found in soy products, displays estrogenic
      properties. The present study aims to investigate the neuroprotective effects of
      genistein on dopaminergic neurons in ovariectomized (OVX), 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. MPTP significantly
      decreased the levels of dopamine (DA) and its metabolites dihydroxyphenylacetic
      acid (DOPAC) and homovanillic acid (HVA) in the striatum, which could be restored
      by genistein or estrogen pretreatment. MPTP-challenge with genistein or estrogen
      pretreatment demonstrated reduced neurotoxicity, with tyrosine hydroxylase
      immunoreactive (TH-IR) neurons in the substantia nigra pars compacta (SNpc)
      affected to a significantly lesser extent as compared to the MPTP treated
      control. The reverse transcription-PCR results also confirmed that the MPTP
      induced downregulation of TH, dopamine transporter (DAT) and Bcl-2 mRNA
      expression in the midbrain could be restored by genistein or estrogen
      pretreatment. These findings provide the first evidence that genistein has
      neuroprotective effects on dopaminergic neurons in the MPTP-induced PD mice and
      this effect may be attributed to enhancing Bcl-2 gene expression.

PMID- 18054105
TI  - Genotype analysis of enterotoxin H-positive Staphylococcus aureus strains
      isolated from food samples in the Czech Republic.
AB  - Twenty-eight enterotoxin H-positive Staphylococcus aureus strains isolated from
      food samples collected in eleven districts of the Czech Republic between 2000 and
      2005 were genotypically characterized by pulsed-field gel electrophoresis (PFGE)
      profiling, spa gene polymorphism analysis, enterobacterial repetitive intergenic
      consensus sequence-based PCR (ERIC-PCR) fingerprinting and prophage carriage
      detection. These strains accounted for about 21% of the food-derived,
      staphylococcal enterotoxin (SE)-positive isolates. One strain, detected in feta
      cheese, was implicated in a case of enterotoxinosis. Sixteen of the twenty-eight
      isolates carried the seh gene alone. The remaining twelve strains harbored the
      seh gene in combination with other enterotoxin genes, most often the seg and sei
      genes, followed by the sea, seb, sec and sed genes. Comparison of various genomic
      profiles resulted in the determination of twenty genotypes designated G-1 to G
      20. Two new, to date not defined, spa types (t2000 and t2002) were identified in
      one strain isolated from raw meat and two strains obtained from prepacked pizza.
      Evidence has been given that the seh-positive S. aureus isolates from foodstuffs
      did not originate from a single source or a common ancestor.

PMID- 18054106
TI  - Characterization of tannase activity in cell-free extracts of Lactobacillus
      plantarum CECT 748T.
AB  - In foods, tannins are considered nutritionally undesirable. Spectrophotometric
      methods have been used to detect tannin degradation by L. plantarum strains
      isolated from food substrates. Enzymatic degradation of tannic acid by L.
      plantarum CECT 748T was examined in liquid cultures and in cell-free extracts by
      HPLC. Significative reduction of tannic acid was not observed during incubation
      in the presence of L. plantarum cells after 7 days incubation. However, tannic
      acid was effectively degraded by cell-free extracts of L. plantarum during 16 h
      incubation. We have partially characterized L. plantarum tannase activity by
      measuring its esterase activity on methyl gallate. Tannase activity was optimal
      at pH 5.0 and 30 degrees C, and showed nearly 75% of the maximal activity at 50
      degrees C. The biochemical characteristics showed by L. plantarum tannase are
      considered favourable for tannin biodegradation in the food-processing industry.

PMID- 18054107
TI  - Supercritical antisolvent production of biodegradable micro- and nanoparticles
      for controlled delivery of paclitaxel.
AB  - Paclitaxel and poly (L-Lactic acid) (PLA) were co-precipitated to form micro and
      submicron particles in a manner similar to that used in the supercritical
      antisolvent with enhanced mass transfer (SAS-EM) process. As compared with
      conventional processes, a major advantage of supercritical CO(2) as an
      antisolvent in the SAS-EM process is the effective removal of residual organic
      solvents. In this work, the organic phase was sprayed into supercritical CO(2)
      (for CO(2), Tc=31.1 degrees C, Pc=73.8 bar) from a 500 microm ID capillary
      nozzle. Ultrasonic vibration with an amplitude of 0 to 120 microm (from a 3/8''
      tip diameter titanium probe) was employed in the high pressure vessel during the
      antisolvent process to provide enhanced mixing between the solvent and
      antisolvent phases. The role and effects of ultrasonication on the properties of
      the resulting particles were studied. When no ultrasonication was applied,
      micrometer-sized particles were obtained. When ultrasonication was applied, more
      uniform particles in the submicron size range were obtained. The size of the
      particles was found to vary with the ultrasonic vibration amplitude.
      Encapsulation efficiencies up to 83.5% and controlled release of paclitaxel for
      more than 30 days were achieved with the particles fabricated in this study.

PMID- 18054108
TI  - Leu54Phe and Val762Ala polymorphisms in the poly(ADP-ribose)polymerase-1 gene are
      associated with diabetic polyneuropathy in Russian type 1 diabetic patients.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is an ubiquitous DNA-binding protein
      involved in the cellular response to various genotoxic agents. Excessive PARP-1
      activation is known to lead to the depletion of intracellular NAD+ and ATP pools
      and hence to threat cell survival. Therefore, PARP-1 could be involved in
      neuronal death and contribute to the development of diabetic polyneuropathy
      (DPN). This study addressed the association of Leu54Phe and Val762Ala
      polymorphisms of PARP-1 with DPN in Russian type 1 diabetic (T1D) patients.
      Eighty-six T1D patients with severe DPN and 93 T1D patients with no clinical
      signs of DPN have been studied by a polymerase chain reaction restriction
      fragment length polymorphism approach. Using Fisher's exact test revealed the
      association of the Phe54 and Val762 variants of PARP-1 (odds ratio (OR), 1.66 and
      2.88, respectively) with increased risk of DPN in T1D. These results suggest that
      the PARP1 gene is involved in the pathogenesis of diabetic neuropathy in a
      Russian population. Additionally, a logistic regression analysis revealed a
      significant association between the neurological variances such as vibration
      detection threshold (OR, 2.08), vibration and temperature perception thresholds
      (OR, 1.32 and 1.67, respectively), and sensory and motor nerve conduction
      velocities (OR, 2.34 and 2.58, respectively), with DPN.

PMID- 18054109
TI  - Economic evidence of influenza vaccination in children.
AB  - OBJECTIVE: We review published economic evaluations of influenza vaccination for
      children, including direct individual benefits and indirect societal benefits, to
      determine whether more studies are needed to fully understand the expected
      benefits of such strategies. METHODS: We searched MEDLINE and EMBASE databases to
      May 2006 and in-press articles to October 2006 for studies including economic
      analyses of influenza vaccination in children. Abstracts of all potentially
      relevant articles were screened. RESULTS: Fifteen relevant articles from 1983
      were retained. Most were based on modelling, using previously published data and
      considered the societal perspective. Three were a part of prospective clinical
      trials. Various paediatric vaccination scenarios and parameters were considered.
      Vaccinating children against influenza was cost saving or cost effective in 10/15
      studies, cost saving or effective only under certain conditions in three studies,
      and not cost saving or effective in two studies whatever the outcome or
      perspective considered. CONCLUSIONS: Most published evidence points to an
      economic interest for society of vaccinating children against influenza. However,
      differences in study design hinder the comparison of the various vaccination
      strategies considered. Comparable and complete data on the burden and cost of
      disease, and the cost of vaccination are needed, especially outside of North
      America.

PMID- 18054110
TI  - Opinion on tobacco tax increase: factors associated with individuals' support in
      Germany.
AB  - OBJECTIVES: To assess the opinion on tobacco tax increases in Germany. DESIGN:
      Ten wave cross-sectional study with assessments before and after the tax
      increases. SETTING: General population of Germany. PARTICIPANTS: Ten
      representative samples from general population with a total number of 27,608
      persons aged 14 and above were interviewed. MAIN OUTCOME MEASURES: Opinion
      ("support", "disapprove", and "undetermined") before and after tobacco tax
      increases. RESULTS: Thirty-nine percent of the sample supported the tobacco tax
      increases. Support was higher among non-smokers and subjects with higher levels
      of education. Data indicated an increase of support over time from 35% in 2002 to
      42% in 2005 which was not affected by the amount of price increase. CONCLUSIONS:
      The preliminary findings, that the amount of price increase did not affect the
      support of the general population in a negative way, and that support grew during
      a succession of tax increases, might be useful for legislators.

PMID- 18054111
TI  - Room for manoeuvre? Explaining local autonomy in the English National Health
      Service.
AB  - Decentralisation has returned as a key theme in English health policy in recent
      years in policies such as Patient Choice and Foundation Trusts, among many
      others. The goal of these policies appears to be to stimulate self-sustaining
      incentives to continuous organisational reform and performance improvement
      through creating a pluralist model of local provision. However, the ability of
      local organisations to exercise autonomy and to deliver such performance is
      highly contingent upon their local context, not least in terms of existing
      patterns of dependencies. Explaining variation in local outcomes of national
      policies demands an understanding and explanation of local autonomy and its
      effect on performance which takes into account the role of the local 'health
      economy'--the local context within which organizations are embedded. It is this
      combination of vertical and horizontal autonomy which effectively determines the
      local room for manoeuvre in decision-making. The aim of the paper is to examine
      the local dimension of decentralisation policies. It draws from different strands
      of literature to discuss the room for manoeuvre of local organisations within
      local health economies in England with specific reference to Primary Care Trusts.
      It draws conclusions about the nature of decentralisation itself and the impact
      of such policies.

PMID- 18054112
TI  - Analysis of satisfaction about new cooperative medical scheme and its influencing
      factors in Weihai, China.
AB  - From 2003, under the principle of raising fund in multiple ways and voluntarily
      jointing in by rural people, trial areas of new cooperative medical scheme (NCMS)
      are increasing year-by-year in China. Meanwhile, more and more farmers
      participate in NCMS with great enthusiasm. In this study, we examined the
      satisfaction about new cooperative medical scheme (NCMS) as well as the factors
      that had an influence on the attitudes towards NCMS. The sample, 4303 countryside
      residents aged > or =15-year, was randomly chosen by using stratified-cluster
      sampling method. Data were evaluated by using percentages, nonparametric tests
      and ordinal regression. As showed in this study, 73.2% of the subjects were
      satisfied with NCMS. According to the results of single factor analysis, the
      attitudes towards NCMS were affected by gender, age, self-rated health status,
      whether having received health check-ups, and hospital stay during 2006, the
      difference proving to be statistically significant (P<0.05). In the ordinal
      regression analysis, it was found that the following factors, age, self-rated
      health status, whether having received health check-ups, and hospital stay during
      2006, had an influence on satisfaction (P<0.05).

PMID- 18054113
TI  - Gaining and losing the thermophilic adaptation in prokaryotes.
AB  - We studied the evolution of thermophily in prokaryotes using the phylogenetic
      relationships between 279 bacteria and archaea and their thermophilic amino acid
      composition signature. Our findings suggest several examples in which the
      capacity of thermophilic adaptation has been gained or lost over relatively short
      evolutionary periods throughout the evolution of prokaryotes.

PMID- 18054114
TI  - Cryptic complexity captured: the Nematostella genome reveals its secrets.
AB  - The full genomic sequence of the sea anemone Nematostella vectensis, which is the
      first full genomic sequence for a representative of the Phylum Cnidaria, has
      recently been published, providing some surprising findings and a unique
      perspective on the evolution of animal genomes. Major conclusions are that, in
      gene number, composition and intron/exon structure, the anemone is more similar
      to vertebrates than are flies and nematodes and that this shared complexity must
      therefore be very ancient.

PMID- 18054115
TI  - Insights into the connection between cancer and alternative splicing.
AB  - Computational and experimental evidence has revealed that cancerous cells express
      transcript variants that are abnormally spliced, suggesting that mRNAs are more
      frequently alternatively spliced in cancerous tissues than in normal ones. We
      show that cancerous tissues exhibit lower levels of alternative splicing than do
      normal tissues. Moreover, we found that the distribution of types of alternative
      splicing differs between cancerous and normal tissues. We further show evidence
      suggesting that the lower levels of alternative splicing in cancerous tissues
      might be a result of disruption of splicing regulatory proteins.

PMID- 18054116
TI  - The haplo-spliceo-transcriptome: common variations in alternative splicing in the
      human population.
AB  - Numerous inherited human genetic disorders are caused by defects in pre-mRNA
      splicing. Two recent studies have added a new twist to the link between genetic
      variation and pre-mRNA splicing by identifying SNPs that correlate with heritable
      changes in alternative splicing but do not cause disease. This suggests that
      allele-specific alternative splicing is a mechanism that accounts for individual
      variation in the human population.

PMID- 18054117
TI  - Cereal breeding takes a walk on the wild side.
AB  - Elite cultivated crop gene pools of the Triticeae tribe (wheat, barley and rye)
      exhibit limited genetic diversity, raising concerns about our ability to increase
      or simply sustain crop yield and quality in the face of dynamic environmental and
      biotic threats. Although exploiting their wild relatives as a source of novel
      alleles is challenging, it has provided notable successes in cereal improvement
      for >100 years. Increasingly facile gene discovery, improved enabling
      technologies for genetics and breeding and a better understanding of the factors
      limiting practical exploitation of exotic germplasm promise to transform
      existing, and accelerate the development of new, strategies for efficient and
      directed germplasm utilization.

PMID- 18054118
TI  - A software package for interactive motor unit potential classification using
      fuzzy k-NN classifier.
AB  - We present an interactive software package for implementing the supervised
      classification task during electromyographic (EMG) signal decomposition process
      using a fuzzy k-NN classifier and utilizing the MATLAB high-level programming
      language and its interactive environment. The method employs an assertion-based
      classification that takes into account a combination of motor unit potential
      (MUP) shapes and two modes of use of motor unit firing pattern information: the
      passive and the active modes. The developed package consists of several graphical
      user interfaces used to detect individual MUP waveforms from a raw EMG signal,
      extract relevant features, and classify the MUPs into motor unit potential trains
      (MUPTs) using assertion-based classifiers.

PMID- 18054120
TI  - [Granulomatosis: a challenge for the internist?].

PMID- 18054119
TI  - A derivative of the melanocortin receptor antagonist SHU9119 (PG932) increases
      food intake when administered peripherally.
AB  - Melanocortin receptors are considered promising candidates for the treatment of
      behavioral and metabolic disorders ranging from obesity to anorexia and cachexia.
      These experiments examined the response of mice to peripheral injections of two
      compounds. PG932 is a derivative of SHU9119 which is non-selective antagonist of
      melanocortin-3 and melanocortin-4 receptors (Mc3r and Mc4r). PG946 is a
      derivative of a hybrid of alpha- and beta-MSH, and is a moderately selective Mc3r
      antagonist. SHU9119 increases food intake when administered
      intracerebroventricularly but is without effect when injected into the periphery.
      In contrast, PG932 was found to be highly effective at stimulating food intake
      when administered peripherally by intraperitoneal injection. The orexigenic
      effect of PG932 required functional Mc4r, suggesting that inhibition of this
      receptor is involved in the stimulation of food intake. PG946 did not
      significantly affect on feeding behavior. PG932 is thus a useful new compound for
      studies examining the regulation of appetite and energy balance, and may also
      prove useful for the treatment of cachectic conditions.

PMID- 18054121
TI  - [Toxic or drug-induced granulomatous reactions].
AB  - PURPOSE: To review the current concepts in toxic and drug-induced granulomatous
      reactions. CURRENT KNOWLEDGE AND KEY POINTS: Granulomatous reactions are induced
      by various chemical agents, treatments or foreign bodies. According to the
      breaking way into the organism, the lungs, the liver, the kidneys or the skin are
      mainly concerned, but systemic granulomatosis mimicking sarcoidosis is possible.
      Therefore systematic analysis of environmental, occupational and leisure
      exposures and quest for medical or illicit drugs is mandatory to identify the
      responsible agent. Over the recent period, chronic beryllium disease, interferon
      alpha therapy, BCG immunotherapy and allopurinol have been more frequently
      involved. FUTURE PROSPECTS AND PROJECTS: Literature review uncovers a variety of
      potential toxic exposures and highlights the necessity of a clear sighted
      research to identify them.

PMID- 18054122
TI  - [Systemic granulomatosis of infectious origin].
AB  - PURPOSE: Granulomatous diseases are defined by specific histological features,
      following the local recruitment of macrophages and lymphocytes. Many infections
      can lead to the development of granuloma. CURRENT KNOWLEDGE AND KEY POINTS:
      Microorganisms responsible for granuloma include mainly mycobacteria, many viral
      and fungal species, as well as schistosoma in endemic areas. Nevertheless, almost
      all microorganisms can lead to granuloma, especially if their clearance needs
      macrophages pathway. New immunosuppressive drugs such as tumor necrosis factor
      antagonists are associated with a high risk of infectious granulomatous
      complications. All patients with granuloma must be carefully screened to find a
      potential underlying infection, since an immunosuppressive therapy could be
      otherwise considered. We here review the general diagnostic process with a
      specific glance to the main organs. FUTURE PROSPECTS AND PROJECTS: Without
      clinical or epidemiological clue, diagnosis can be very tedious. New molecular
      tools now assist classical microbiological and histological techniques. Their
      specificity and sensitivity have recently been better characterized, and their
      use will probably increase in the near future for the diagnosis of infectious
      granuloma. They may also lead to discover new infectious aetiologies of
      granulomatous diseases formerly considered as idiopathic. We describe here the
      main microorganisms that can be responsible for granuloma, with a specific focus
      on the use of new diagnostic tools.

PMID- 18054123
TI  - [Granulomatous disease in common variable immunodeficiency].
AB  - PURPOSE: Common variable immunodeficiency (CVID), defined by defective production
      of immunoglobulins, is the most common primary immunodeficiency in adulthood
      requiring a medical follow-up. Repeated bacterial infections and/or autoimmune
      manifestations and/or benign lymphoproliferation (including follicular
      hyperplasia and/or granulomatous disease) are the hallmark of the disease. This
      review aims at describing recent advances in the understanding and treatment of
      granulomatous disease in CVID. CURRENT KNOWLEDGE AND KEY POINTS: Clinical
      features of granulomatous disease in CVID can mimic sarcoidosis, remarkable by
      the low levels of circulating immunoglobulins. Granulomas may be found in several
      organs in a single patient, and the main features are pulmonary, lymphoid,
      cutaneous, hepatic or splenic. The features of CVID is remarkable by the high
      frequency of autoimmune diseases complicating the immunodeficiency. Some
      immunological abnormalities have been described in such patients, including
      lymphopenia, decreased T-cells proliferations to mitogens and antigens. Rare
      polymorphisms in the gene encoding TNFalpha (Tumor Necrosis Factor) have been
      identified in CVID patients with granulomatous disease. FUTURE PROSPECTS AND
      PROJECTS: The evolution of the disease is severe, particularly when the lung is
      involved. Treatment consists in immunoglobulins substitution, immunosuppressive
      agents (corticosteroids, cyclophosphamide) and anti-TNFalpha antibodies. These
      treatments are difficult to manage in such immunocompromised patients.

PMID- 18054124
TI  - [Sarcoidosis and sarcoid reactions in cancer].
AB  - PURPOSE: Relationships between granulomatosis and cancers have been suspected for
      a long time. Nevertheless, few evidence has been reported until recently. Here,
      we present a literature review about the association of granulomatosis and
      neoplasia. CURRENT KNOWLEDGE AND KEY POINTS: Aside from granulomatosis due to
      infectious disease, granulomas can be observed in cancer patients, mainly in two
      situations. Patients may rarely present with typical sarcoidosis occurring
      before, during or after the diagnosis of cancer. Recent studies have documented
      such a relationship particularly with lymphomas, testicular and lung cancers,
      melanomas and hepatocarcinomas. Secondly granulomas may be found as a sarcoid
      reaction in the vicinity of the tumour itself or more frequently in regional
      lymph nodes. Sarcoid reaction, reported in Hodgkin's disease and gastric
      adenocarcinomas, may be associated with a better prognosis. Granulomatous
      reaction could play an important role in the host's defences against metastatic
      extension. Immunotherapy such as interferon has been reported to induce systemic
      sarcoidosis probably by reproducing some physiopathological mechanisms involved
      in sarcoidosis. FUTURE PROSPECTS AND PROJECTS: Clinicians need novel non invasive
      diagnostic methods to differentiate neoplasia from benign sarcoid reactions. The
      18-fluorodeoxyglucose (18-FDG) PET-scan has failed in this indication but the
      adjunction of a [3-(18)F]-alpha-methyltyrosine ((18)F-FMT) PET-scan could be
      useful. Biopsies is still necessary in most of cases.

PMID- 18054125
TI  - [Atypical sarcoidosis].
AB  - PURPOSE: Sarcoidosis is a granulomatous disease of unknown etiology. Lung and
      lymphatic system are the principal localisations. Clinical presentations are
      various depending on involved organs. Some presentations, which are easily
      diagnosed, are typical and frequent. Atypical forms have unusual presentations
      and/or are rare. Beside, in a multisystemic sarcoidosis, the affection of only
      one organ can be unusual. Rigorous diagnosis procedure could avoid errors.
      CURRENT KNOWLEDGE AND KEY POINTS: Twenty percent of sarcoidosis have atypical
      presentation. However, each of them are infrequent. Atypical features are wide
      and can concern pulmonary or extrapulmonary manifestations, general
      manifestations, blood testing or pathological pattern. FUTURE PROSPECTS AND
      PROJECTS: Describing atypical forms are necessary for their diagnosis. The
      diagnosis of atypical sarcoidosis is found on the knowledge of atypical forms
      previously described, presence of granulomas on specimen biopsy and excluding
      other granulomatous disease.

PMID- 18054126
TI  - Expression and purification of a Plasmodium vivax antigen - PvTARAg55 tryptophan-
      and alanine-rich antigen and its immunological responses in human subjects.
AB  - Despite the immense global efforts, the malaria vaccine is not yet available and
      requires the identification of newer target molecules. Since tryptophan-rich
      proteins of P. yoelii have been proposed as vaccine candidates, we describe here
      the expression, purification and immunological characterization of a 55kDa
      Plasmodium vivax tryptophan- and alanine-rich antigen (PvTARAg55). This protein
      consists of 480 aa residues with a calculated molecular mass of 55.0kDa. It shows
      42% aa sequence identity (64% homology) with PyPAg1 of P. yoelii and shares
      positional conservation of tryptophan residues. Sequence analysis of PvTARAg55
      from different P. vivax isolates revealed that typtophan-rich domain which
      contains most of the B-cell epitopes was highly conserved in the parasite
      population while the alanine-rich domain showed polymorphism. Exon-2 covering
      major part (420 aa) of the protein including both the domains was PCR amplified,
      cloned, expressed in Escherichia coli, and the recombinant protein purified to
      its homogeneity. Majority of P. vivax-infected individuals (82.5%, n=40) produced
      antibodies against this antigen. Proliferative responses to the recombinant
      PvTARAg55 were observed in 60% (n=20) of individuals who had recently been
      exposed to the P. vivax infection. Measurement of Th1- (IFN-gamma, TNF-alpha, and
      IL-12) and Th2-type (IL-4 and IL-10) cytokine production in response to this
      recombinant antigen revealed a mixed type T-cell response with a Th2 response
      being more pronounced. These results demonstrate that PvTARAg55 elicits high
      humoral and cellular immune responses thus establishes its immunogenecity in
      humans.

PMID- 18054127
TI  - The impact of a new universal infant and school-based adolescent hepatitis B
      vaccination program in Australia.
AB  - We compared the results of two national serosurveys in Australia to evaluate the
      impact of universal infant vaccination and school-based programs for adolescents.
      Immunity improved significantly overall, especially in 1-year-olds (40.0% versus
      86%; p<0.0001); in adolescents it was significantly higher in regions with
      established school-based programs (56.6% versus 38.8%; p=0.0008). 6.1% of 1-59
      year-olds were positive for HBcAb and 0.7% for HBsAg. We have demonstrated
      successful implementation of universal infant hepatitis B vaccination in
      Australia and that school-based programs for adolescents are effective. This
      experience should be applicable to low prevalence countries in northern Europe
      which have not implemented universal hepatitis B immunisation.

PMID- 18054128
TI  - Radiation-induced adaptive response in fish cell lines.
AB  - There is considerable interest at present in low-dose radiation effects in non
      human species. In this study gamma radiation-induced adaptive response, a low
      dose radiation effect, was examined in three fish cell lines, (CHSE-214 (Chinook
      salmon), RTG-2 (rainbow trout) and ZEB-2J (zebrafish)). Cell survival after
      exposure to direct radiation with or without a 0.1 Gy priming dose, was
      determined using the colony forming assay for each cell line. Additionally, the
      occurrence of a bystander effect was examined by measuring the effect of
      irradiated cell culture medium from the fish cell lines on unexposed reporter
      cells. A non-linear dose response was observed for all cell lines. ZEB-2J cells
      were very sensitive to low doses and a hyper-radiosensitive (HRS) response was
      observed for doses <0.5 Gy. A typical protective adaptive response was not
      detected in any of the three fish cell lines tested. Rather, it was found that
      pre-exposure of these cells to 0.1 Gy radiation sensitized the cells to
      subsequent high doses. In CHSE-214 cells, increased sensitivity to subsequent
      high doses of radiation was observed when the priming and challenge doses were
      separated by 4 h; however, this sensitizing effect was no longer present when the
      interval between doses was greater than 8 h. Additionally, a "protective"
      bystander response was observed in these cell lines; exposure to irradiated
      medium from fish cells caused increased cloning efficiency in unirradiated
      reporter cells. The data confirm previous conclusions for mammalian cells that
      the adaptive response and bystander effect are inversely correlated and contrary
      to expectations probably have different underlying mechanisms.

PMID- 18054129
TI  - 127I and 129I/127I isotopic ratio in marine alga Fucus virsoides from the North
      Adriatic Sea.
AB  - The only stable iodine isotope is 127I and the natural 129I/127I ratio in the
      biosphere has increased from 10(-15)-10(-14) to 10(-10)-10(-9), mainly due to
      emissions from nuclear fuel reprocessing plants. In Europe they are located at La
      Hague (France) and Sellafield (England), where the ratio of 129I/127I is up to
      10(-4). The marine environment, i.e. the oceans, is the major source of iodine
      with average concentrations of around 60 mirogL(-1) iodine in seawater. Brown
      algae accumulate iodine at high levels of up to 1.0% of dry weight, and therefore
      they are an ideal bioindicator for studying the levels of 127I and 129I in the
      marine environment. A radiochemical neutron activation analysis (RNAA) method,
      developed at our laboratory, was used for 129I determination in the brown alga
      Fucus virsoides (Donati) J. Agardh, and the same technique of RNAA was used for
      total 127I determination. The samples were collected along the coast of the Gulf
      of Trieste and the West coast of Istria in the North Adriatic Sea in the period
      from 2005 to 2006. Values of the 129I/127I ratio up to 10(-9) were found, which
      is in agreement with the present average global distribution of 129I. The levels
      of stable iodine found were in the range from 235 to 506 microg g(-1) and the
      levels of 129I from 1.7 to 7.3 x 10(-3)Bq kg(-1) (2.6-10.9 x 10(-7) microg g(
      1)), on a dry matter basis.

PMID- 18054130
TI  - The neurologist, psychogenic nonepileptic seizures, and borderline personality
      disorder.
AB  - Patients with psychogenic nonepileptic seizures (PNES) are common in tertiary
      epilepsy centers, emergency departments, and neurological practices. Psychiatric
      discussion of patients with PNES has emphasized the role of trauma and
      dissociation. Personality disorder has been considered, but its extensive
      implications for neurological management have not been fully appreciated. We
      propose that the most difficult aspects of management stem not from the
      convulsive episodes, but from the personality disorder that frequently
      accompanies them. Although it is not the neurologist's role to treat personality
      disorder, the conduct of the physician-patient relationship can have potent
      consequences for good or ill on the outcome. We present a brief guide to current
      concepts of personality disorder; discuss the literature concerning its
      association with PNES, and offer practical guidelines for the conduct of the
      neurologist-patient relationship. This perspective offers resolutions to
      longstanding controversies, including how to communicate the diagnosis,
      discontinuing medication, and ongoing neurological contact.

PMID- 18054131
TI  - Ictal nausea with vomiting as the major symptom of simple partial seizures:
      electroencephalographic and magnetoencephalographic analysis.
AB  - Autonomic symptoms and signs rarely occur as isolated phenomena without impaired
      consciousness. Ictal nausea with vomiting is a rare clinical manifestation of
      seizures. Ictal vomiting is considered a localizing sign in patients with partial
      seizures of temporal origin. We encountered two patients with simple partial
      seizures that produced nausea with vomiting as the sole symptom, and we describe
      the interictal electroencephalographic and magnetoencephalographic findings. The
      episodes were paroxysmal and stereotypical in nature, and patients showed
      symptomatic response to a trial of antiepilepsy medication. In both patients, the
      diagnosis was simple partial seizures with autonomic symptomatology. Although
      interictal electroencephalography did not reveal focal spikes and focal slowing,
      estimated magnetoencephalographic dipoles were clustered in the parietal lobe.
      Interictal magnetoencephalographic foci may serve only as subsidiary evidence for
      the parietal origin of the episodes. However, our findings provide evidence of
      additional involvement of the parietal lobe in ictal vomiting.

PMID- 18054132
TI  - December: retrospection month.

PMID- 18054133
TI  - The prospect of pandemic influenza: why should the optometrist be concerned about
      a public health problem?
AB  - BACKGROUND: Optometrists are uniquely placed in the health care field because
      they provide both services as well as goods to patients. In the event of an
      influenza pandemic, optometrists may be challenged with a host of issues,
      including impediments to clinical patient care, manufacture and delivery of
      ophthalmic devices, and maintaining business continuity and infection control.
      OVERVIEW: This report reviews pandemic influenza, the effect of a pandemic event
      on business survival, and response measures for the primary eye care provider.
      The ethical and legal issues surrounding control of a pandemic influenza and the
      prospect of telemedicine as a form of social distancing are also discussed.
      CONCLUSIONS: Knowledge of the pharmacologic and nonpharmacologic measures to
      control a pandemic influenza will help prepare the eye care provider for
      addressing challenges to patient care and business continuity in the face of a
      highly contagious disease. Understanding the legal and ethical issues that arise
      during a pandemic event will help optometrists make informed choices as health
      care professionals and as citizens.

PMID- 18054134
TI  - An optometric approach to patients with sensory integration dysfunction.
AB  - BACKGROUND: Sensory integration dysfunction is a neurologic condition that can
      cause children to process environmental sensations in an inappropriate way. As a
      result, they may either seek out strong sensations or avoid even mild sensations.
      Some of the characteristics of these children may be hyperactivity, poor
      awareness of pain, high risk taking, listening to loud sounds, clumsiness, poor
      fine motor skills, poor gross motor skills, poor visual tracking, problems with
      sequencing, and problems with balance. Sensory integration dysfunction often is
      related to children with developmental disabilities, autism, and attention
      deficits. METHODS: Two children from the same family were examined for general
      eye examinations because of a history of sensory integration problems. J.H., an
      11-year-old girl, and her 6-year-old half-brother, A.T., returned to the clinic
      for visual-perceptual testing: the Test of Variables of Attention (TOVA), the
      Developmental Eye Movement Test (DEM), and the Visagraph (Compevo AB, Stockholm,
      Sweden). The use of yoked prisms with these children was also explored. RESULTS:
      Both children showed oculomotility problems based on the DEM and Visagraph
      results. Whereas J.H. performed well on the visual-perceptual profile overall,
      A.T. showed problems in many areas such as reversals, visual spatial relations,
      visual sequential memory, visual form constancy, and attention. Both children
      were low hyperopes and showed positive postural and balance changes when tested
      with yoked prisms. CONCLUSIONS: Children with sensory integration dysfunction can
      have a number of signs and symptoms that may bring them to the optometrist's
      office. It is important to thoroughly test their visual, perceptual, and
      oculomotor systems to determine the best way to help these patients. The use of
      vision therapy and yoked prisms can be beneficial treatment options for many of
      these patients.

PMID- 18054135
TI  - Prescription and management of contact lenses in patients with monocular visual
      impairment.
AB  - PURPOSE: Contact lens correction for refractive error in patients with monocular
      visual impairment may be desirable. However, the potential for damage to the
      sound eye must always be considered in such patients. This report outlines the
      prescription and management of contact lens wear in a monocular patient. The case
      report is followed by a discussion of the risks of vision loss associated with
      contact lens wear. CASE REPORT: The author conducted a clinical interview,
      refraction, ocular examination, and contact lens evaluation of a 38-year-old
      female patient who had undergone a lensectomy in her right eye and the
      enucleation of her left eye. The patient presented wearing a conventional aphakic
      hydrogel contact lens in her right eye. She routinely wore her contact lens for
      up to 16 hours daily and occasionally slept while wearing it. Best-corrected
      spectacle acuity was 20/40-2 with +13.75 diopter sphere in her right eye.
      Clinical examination showed 3 to 4 mm of well-perfused neovascularization with
      associated pannus in the superior quadrant of her cornea and 1 to 2 mm of
      peripheral neovascularization in the remainder of the cornea. She was refit with
      a 2-week replacement hydrogel contact lens that partially corrected her
      refractive error, and she was encouraged to wear polycarbonate spectacles full
      time for the remainder of her refractive correction and for protection of the
      right eye. CONCLUSIONS: Monocularly impaired patients who choose to wear contact
      lenses for the correction of refractive error should be aware of the risk of
      potentially sight-threatening contact lens complications. The importance of
      meticulous hygiene and appropriate contact lens wearing schedules should be
      emphasized with monocular patients. They should also be encouraged to wear the
      appropriate spectacle correction to reduce the risk of injury to their sound
      eyes.

PMID- 18054136
TI  - Detection of glaucoma-like optic discs in a diabetes teleretinal program.
AB  - BACKGROUND: Glaucoma is typically an insidious-onset disease with serious visual
      consequences that has been positively linked to diabetes mellitus (DM) in several
      studies. We assessed the sensitivity and specificity of a diabetes teleretinal
      program to identify the glaucoma-suspicious optic disc. METHODS: Outpatients with
      DM (N = 1,644) presenting to Veterans Affairs ambulatory clinics participated in
      a nonmydriatic digital retinal imaging (NMDRI) program. Technicians transmitted
      digital retinal images electronically to readers for grading and eye care
      recommendations. Patients were referred for ophthalmic care based on the level of
      diabetic retinopathy and other ocular findings, including optic nerve changes
      suspicious for glaucoma. We retrospectively reviewed the electronic medical
      records of patients labeled as glaucoma suspects (N = 175) and compared them with
      those of patients from the same imaging pool who were not regarded as glaucoma
      suspects (N = 175). Ophthalmic data obtained from a comprehensive eye examination
      after digital retinal imaging was used to determine which patients met predefined
      criteria for the optic disc suggestive of glaucoma. RESULTS: Assessment of
      clinical data obtained after NMDRI found that 103 of 175 (59%) glaucoma suspects
      had glaucoma-suspicious optic discs. In the comparison group, only 7 of 175 (4%)
      had glaucoma-suspicious optic discs. CONCLUSIONS: Although specificity was high
      (96%), modifications in diabetes teleretinal imaging programs are needed to
      improve the sensitivity of detecting the optic disc that is suspicious for
      glaucoma.

PMID- 18054137
TI  - Exam room, chair side evaluation of retinal edema: improving accuracy and
      precision for identification of subclinical diabetic macular edema.
AB  - BACKGROUND: Early detection of diabetic macular edema (DME) is important for
      improving patient outcomes. Currently, the gold standards are slit lamp stereo
      biomicroscopy examination and fluorescein angiography (FA). Detecting DME with a
      slit lamp is subjective and can be difficult in the early stages of the disease.
      FA is invasive and involves discomfort and risk to the patient. A new diagnostic
      test, the Heidelberg Retina Tomograph (HRT) Retina Module (Heidelberg
      Engineering, Heidelberg, Germany), is noninvasive, objective, and sensitive to
      early changes in the retina. It is purported to locate and quantify retinal edema
      such as DME, independent of retina thickening. Presented are a series of case
      reports comparing retinal photography, FA, HRT, and ocular coherence tomography
      (Stratus OCT; Carl Zeiss Meditec, Jena, Germany) results on patients with DME.
      The purpose is to determine the clinical utility of the HRT for discerning DME
      compared with clinical stereo biomicroscopy impression and FA. CASE REPORTS: In
      this representative case series, the author's first stereo biomicroscopy
      impression, macular photographs, retinal fluorescein angiographs, Stratus OCT
      images, and HRT Retina Module images from 5 type 2 diabetic patients (3 insulin
      and 2 non-insulin dependent) with retinopathy are presented. All patients are
      men, with a mean age of 56.4 (range, 51 to 62). Subjects had diabetes mellitus
      type 2 for an average of 14.4 years (range, 10 to 22) and were experiencing
      fluctuations or loss in vision. In all cases, DME was clearly identifiable on FA
      although sometimes questionable by stereo biomicroscopy. Nonstereo retinal photos
      and OCT examinations were inconclusive or unremarkable in 4 of 5 cases. The HRT
      Edema surrogate "e" index and map results showed areas of DME that were very
      similar to those of the FA images. CONCLUSIONS: In this case series, the HRT
      Retina Module provided useful clinical information on DME patients including the
      quantification and extent of both subclinical and clinically significant DME.
      Although more rigorous study is warranted, such immediate feedback from a
      noninvasive, safe, diagnostic tool is invaluable in clinical practice,
      particularly with the advent of prophylactic nutritional genistein-based
      multivitamin supplements such as Bausch & Lomb Ocuvite DF (Rochester, New York).

PMID- 18054140
TI  - The diagnostic workup of patients with neuropathic pain.
AB  - Neuropathic pain is initiated or caused by damage or dysfunction of the
      peripheral or central nervous systems in various disorders, each having pain
      related symptoms and signs thought secondary to common pain mechanisms. Ancillary
      testing may demonstrate associated nervous system abnormalities, however its
      specificity is inadequate at present, as it makes inferential conclusions from
      indirect data. Symptom assessment and physical findings remain paramount in the
      diagnosis of neuropathic pain.

PMID- 18054141
TI  - Behavioral medicine approaches to pain.
AB  - Pain is a complex, idiosyncratic experience. When pain is the primary complaint
      for seeking medical attention, understanding of multiple factors is essential in
      guiding successful treatment. Behavioral medicine, a branch of psychology, has
      been an integral part of interdisciplinary/multidisciplinay care of pain
      patients. In this article, we provide an overview of behavioral medicine
      approaches to pain, including assessment and commonly used therapeutic methods.
      Particular attention is given to cognitive-behavioral therapy and motivational
      enhancement therapy.

PMID- 18054142
TI  - Physical medicine rehabilitation approach to pain.
AB  - A physical medicine and rehabilitation approach to acute and chronic pain
      syndromes includes a wide spectrum of treatment focus. Management includes an
      assessment and treatment model based on a biopsychosocial approach. Assessment
      includes a focus on pain behaviors, posture, muscle imbalances, and gait
      impairments. Effective treatment programs rely on appropriate and realistic goal
      setting. Treatment options may include physical therapy, polypharmacy, cognitive
      behavioral therapy, and passive modalities. Treatment goals emphasize achieving
      analgesia, improving psychosocial functioning, and reintegration of recreational
      or leisure pursuits. More complicated multidimensional chronic pain conditions
      may require a more collaborative continuum of multidisciplinary and
      interdisciplinary treatment approaches. Progress in all therapies necessitates
      close monitoring by the health care provider and ongoing communication between
      members of the treatment team.

PMID- 18054143
TI  - Nonopioid analgesics.
AB  - Nonopioid analgesics represent a varied collection of analgesic agents, many of
      which also possess antipyretic or anti-inflammatory actions. As a group,
      nonopioid analgesics represent reasonable first-line analgesics for a variety of
      mild to moderate painful conditions and also often may be useful in conjunction
      with other analgesics (eg, opioids) for a myriad of severe painful conditions.
      Clinicians treating pain should be familiar with the actions, adverse effects,
      and individual agents in the group of nonopioid analgesics.

PMID- 18054144
TI  - Adjuvant analgesics.
AB  - Adjuvant analgesics represent a diverse group of drugs that were originally
      developed for a primary indication other than pain. Many of these medications are
      currently used to enhance analgesia under specific circumstances. The proper use
      of adjuvant drugs is one of the keys to success in effective pain management.
      Since adjuvant analgesics are typically administered to patients who take
      multiple medications, decisions regarding administration and dosage must be made
      with a clear understanding of the stage of the disease and the goals of care. The
      article discusses major classes of adjuvant analgesics, with the focus on the
      mechanism of action, clinical application, and risks and benefits associated with
      each particular class of adjuvants.

PMID- 18054145
TI  - Opioids for persistent noncancer pain.
AB  - This article concentrates on recent evidence about opioid analgesics for
      persistent noncancer pain. Evidence confirms that opioids are drugs with a
      definite risk of adverse events. Therefore, before prescribing opioids, careful
      consideration must be given to be certain that the intended benefit of a
      particular opioid merits its use despite the potential side effects and to
      determine if the co-prescription of other pharmacologic agents could reduce the
      risk of adverse events. Strong opioids should be reserved for patients who fail
      to respond to other lower-risk options and only after proper consideration is
      given to the long-term consequences of strong opioid use. Problems associated
      with opioids dictate that more efficacious and safer drugs need to be found.

PMID- 18054146
TI  - Documentation and potential tools in long-term opioid therapy for pain.
AB  - The field of pain medicine is experiencing increased pressure from regulatory
      agencies and other sources regarding the continuation, or even initial use, of
      opioids in pain patients. Therefore, it is essential that pain clinicians provide
      rationale for engaging in this modality of treatment and provide ample
      documentation in this regard. Thus, assessment and documentation are cornerstones
      for both protecting your practice and obtaining optimal patient outcomes while on
      opioid therapy. Several potential tools and documentation strategies are
      discussed that will aid clinicians in providing evidence for the continuation of
      this type of treatment for their patients.

PMID- 18054147
TI  - Topical analgesics.
AB  - Historically, analgesics were applied by the topical route of administration.
      With the advent of oral formulations of drugs, topical application became less
      popular among physicians, although patients still rated this method of drug
      delivery as efficacious and practical. We now appreciate that peripheral
      mechanisms of actions of a variety of preparations rationalizes their topical
      application and gives further opportunity to target peripheral receptors and
      neural pathways that previously required systemic administration to achieve
      therapeutic effect. Therefore, a peripheral effect can be generated by using
      locally applied drug and, consequently, systemic concentrations of that drug may
      not reach the level at which systemic side effects can occur.

PMID- 18054148
TI  - Myofascial trigger points.
AB  - Painful conditions of the musculoskeletal system, including myofascial pain
      syndrome, constitute some of the most important chronic problems encountered in a
      clinical practice. A myofascial trigger point is a hyperirritable spot, usually
      within a taut band of skeletal muscle, which is painful on compression and can
      give rise to characteristic referred pain, motor dysfunction, and autonomic
      phenomena. Trigger points may be relieved through noninvasive measures, such as
      spray and stretch, transcutaneous electrical stimulation, physical therapy, and
      massage. Invasive treatments for myofascial trigger points include injections
      with local anesthetics, corticosteroids, or botulism toxin or dry needling. The
      etiology, pathophysiology, and treatment of myofascial trigger points are
      addressed in this article.

PMID- 18054149
TI  - Intra-articular injections.
AB  - Intra-articular injections are one method that physicians may use to treat joint
      pain. This method offers direct access to the source of pain for the troubled
      patient. Substances ranging from steroids to hyaluronic acid have been injected
      successfully into the various joints of the body in an attempt to provide relief
      for chronic joint pain. Anesthesiologists and orthopedic surgeons have begun to
      use intra-articular injections of local anesthetics for postoperative analgesia.
      The history, agents, and methods of intra-articular injections are reviewed.

PMID- 18054150
TI  - Intrathecal analgesia.
AB  - Since the first use of intrathecal (IT) drug infusion systems in the early 1980s,
      these delivery systems have undergone numerous revisions making them more
      tolerable, easier to program, and longer lasting. Concurrent with technological
      advances, the indications for IT pump placement have also been continuously
      evolving, to the point where the most common indication is now noncancer pain.
      This article provides an evidence-based review of the indications, efficacy, and
      complications of IT drug therapy for the most commonly administered spinal
      analgesics.

PMID- 18054151
TI  - Interventional approaches to pain management.
AB  - This article reviews the evidence for several common interventional techniques
      for the treatment of chronic pain, including: intraspinal delivery of analgesics,
      reversible blockade with local anesthetics, augmentation with spinal cord
      stimulation, and ablation with radiofrequency energy or neurolytic agents. The
      role of these techniques is defined within the framework of a multidisciplinary
      approach to the neurobehavioral syndrome of chronic pain. Challenges to the study
      of the analgesic efficacy of procedural interventions are explored, as are the
      practical issues raised by their clinical implementation, with the aim of helping
      nonspecialist physicians identify the patients most likely to benefit from these
      approaches.

PMID- 18054152
TI  - Invasive and minimally invasive surgical techniques for back pain conditions.
AB  - This article summarizes current issues related to invasive and minimally invasive
      surgical techniques for back pain conditions. It describes pain generators and
      explains theories about how discs fail. The article discusses techniques for
      treating painful sciatica, painful motion segments, and spinal stenosis. Problems
      related to current imaging are also presented. The article concludes with a
      discussion about physical therapy.

PMID- 18054153
TI  - Vertebroplasty and kyphoplasty.
AB  - Vertebral compression fractures occur more frequently than hip and ankle
      fractures combined. These fragility fractures frequently result in both acute and
      chronic pain, but more importantly are a source of increased morbidity and
      possibly mortality. Percutaneous veretebral augmentation offers a minimally
      invasive approach for the treatment of vertebral compression fractures. The
      history, technique, and results of vertebroplasty and kyphoplasty are reviewed.
      Both methods allow for the introduction of bone cement into the fracture site
      with clinical results indicating substantial pain relief in approximately 90% of
      patients.

PMID- 18054154
TI  - CXCL14 expression and potential function in pancreatic cancer.
AB  - CXC chemokines influence angiogenesis, growth, and metastatic potential of
      pancreatic cancer. Therefore, the expression and potential function of CXCL14, a
      recently described CXC chemokine, was evaluated. CXCL14 is upregulated in
      pancreatic cancer tissues compared to chronic pancreatitis and normal pancreas.
      Immunolocalization revealed a distinct expression of CXCL14 in tubular complexes
      in chronic pancreatitis and in particular at the invasive front of pancreatic
      cancer tissues. Stimulation of pancreatic cancer cells with CXCL14 showed no
      effects on cell viability and on chemosensitivity. However, CXCL14 clearly
      increased invasiveness of pancreatic cancer cells without affecting MMP-2 and
      VEGF secretion, whereas CXCL14 influenced NFkB p65 levels. In conclusion, CXCL14
      might play a pivotal role in the pathobiology of pancreatic cancer, probably by
      regulating cancer invasion.

PMID- 18054155
TI  - Ceramide induces p38 MAPK-dependent apoptosis and Bax translocation via
      inhibition of Akt in HL-60 cells.
AB  - Ceramide induces apoptosis through caspase activation, cytochrome c release, and
      Bax translocation in HL-60 cells. However, the upstream signal transduction
      pathways that induce Bax translocation during ceramide-mediated apoptosis have
      not been well defined yet. In this study, the activation of p38 mitogen-activated
      protein kinase (MAPK) was found to be critical for the induction of apoptosis and
      subcellular redistribution of Bax. Pharmacological inhibition of p38 MAPK with
      SB203580 or expression of a dominant-negative p38 MAPK attenuated DNA
      fragmentation, caspase-3 activation, and Bax translocation in response to
      ceramide. Overexpression of Akt also led to suppression of Bax translocation to
      mitochondria during ceramide-induced apoptosis in HL-60 cells. We also provide
      evidence for cross-talk between p38 MAPK and Akt pathways. Expression of myr-Akt
      or inhibition of phosphatidylinositol 3-kinase (PI3K) with LY294002 had no effect
      on p38 MAPK activation by ceramide as assessed by phosphorylation, while
      inhibition of p38 MAPK by a pharmacological inhibitor or a dominant-negative p38
      inhibited Akt dephosphorylation in response to ceramide, suggesting that ceramide
      induced p38 MAPK activation negatively regulates the Akt pathway.

PMID- 18054156
TI  - Recovery of valuable elements from spent Li-batteries.
AB  - This work examines two recycling processes for spent Li/MnO(2) and Li-ion
      batteries. The anode, cathode and electrolyte (LiPF(6)) were submitted to one of
      the following procedures: (a) calcination at 500 degrees C (5h) followed by
      solvent extraction to recover lithium salts (fluoride, phosphate) in good yield
      (90 wt%). The residual solid was treated with H(2)SO(4) containing H(2)O(2) and
      on evaporation gave high purity grade cobalt or manganese sulfate; (b) fusion
      with KHSO(4) (500 degrees C, 5h). The resulting aqueous solution was added
      dropwise to a solution of NaOH, giving cobalt or manganese as impure precipitate.
      Addition of KF precipitated high purity grade LiF in moderate yield (50 wt%). The
      final aqueous solution on treatment with calcium sulfate precipitated the
      corresponding phosphate and fluoride salts.

PMID- 18054157
TI  - The influence of low atmospheric pressure on carbon monoxide of n-heptane pool
      fires.
AB  - Qualitative theoretical analysis about air pressure influence upon the gas
      concentration of a fire plume was given, different scale n-heptane pool fires
      were conducted in a small and a standard compartment room in Lhasa and Hefei,
      respectively. The experimental results show that, in Lhasa, the average mass
      burning rates in the small room and the standard room both decrease, burning time
      increases at about 53% in small room and 45% in standard room more than in Hefei.
      Whereas for maximum changes of CO concentration, in the small room, in Lhasa, CO
      concentrations reach about twice bigger peak values at larger increase rates than
      in Hefei. While in the standard room, in Lhasa and Hefei, there are no
      significant changes for CO concentration, which agrees well with the theoretical
      analysis results.

PMID- 18054158
TI  - Effect of various chelating agents on supercritical carbon dioxide extraction of
      indium(III) ions from acidic aqueous solution.
AB  - Indium and its compounds have numerous industrial applications in the manufacture
      of liquid crystal displays and semiconductors. Indium compounds are considered
      hazardous materials that can be carcinogenic. Supercritical fluid extraction
      using carbon dioxide was utilized in this research as a sample pretreatment step
      for extraction of indium(III) ions from the synthetic etching wastewater of the
      semiconductor and optoelectronic industries. Several parameters, including
      various chelating agents, pH of solution, molar ratio of chelating agent to
      indium(III) ions, temperature and pressure were systematically investigated.
      Indium(III) ions were extracted by supercritical CO2 combined with several
      various types of chelating agents including beta-diketone (AcAcH), fluorinated
      beta-diketone (TTAH), thiopyridine (PySH), and piperidinyldithiocarbamic acid
      (NCS2H) to extract the ions from acidic aqueous solution. The performance of the
      various chelating agents from different studies indicated that the extraction
      efficiency by the supercritical CO2 was in the order: NCS2H>or==PySH>TTAH>>AcAcH.
      The optimum pH for supercritical CO2 extraction should fall in the range from 2.0
      to 3.0. The optimum molar ratio of chelating agents to indium(III) ions was found
      to be a ratio of 10:1. It was also revealed that the optimal extraction pressure
      and temperature for the supercritical CO2 extraction of indium(III) with various
      chelating agents AcAcH, PySH and NCS2H were 70 degrees C 2000 psi, 60 degrees C
      2000 psi, and 60 degrees C 2000 psi, respectively.

PMID- 18054159
TI  - EDTA impact on Cd2+ migration in apatite-water system.
AB  - The impact factors on Cd sorption and desorption in aqueous solution on apatite
      were studied. Batch experiments were carried out using synthetic hydroxyapatite
      with Ca/P 1.44, 1.66 and 1.94 in Cd(NO3)2 and Cd(NO3)2-EDTA equimolar complex
      solutions in the pH range from 4 to 7. It was established that Cd sorption on
      apatite depends not only on apatite specific surface area but also on Ca/P mole
      ratio in apatite as well as on the presence of chelating compounds. Presence of
      EDTA in the solution decreases the amount of Cd bound. [CdEDTA]2- prevents
      chemical sorption of Cd2+ ions on apatite. EDTA considerably decreases the
      sorption capacity of apatite with Ca excess. Impact of EDTA is smaller for the
      stoichiometric apatite and for the apatite with calcium deficiency. Cd bound due
      to adsorption is more easily removed from apatite. Ca2+ ions increase and
      presence of EDTA in a solution cause total Cd desorption from apatite.

PMID- 18054160
TI  - Evaluation of gas-particle partition of dioxins in flue gas I: evaluation of
      gasification behavior of polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofurans in fly ash by thermal treatment.
AB  - The gasification behavior of polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs) in fly ash by thermal treatment has been
      investigated to estimate gas-particle partition in flue gas. The results obtained
      in thermal experiments under various conditions showed that gasification of
      PCDD/Fs depends on air flow rate and treatment weight of fly ash as well as
      treatment temperature. On the other hand, the results obtained in the thermal
      experiments using dioxin-free fly ash revealed that during thermal treatment, the
      de novo synthesis, gasification, and decomposition of PCDFs proceeded at
      different rates. This difference in the reaction rates indicates that thermal
      treatment time is also a factor in determining the gas-particle partition of
      PCDD/Fs in fly ash. Therefore, reasonable thermal treatment conditions were
      established and applied to three ash samples. For all samples, PCDD/Fs started to
      gasify at 350 degrees C treatment, whereas 53-98% of PCDD/F homologs gasified at
      400 degrees C treatment, implying that gaseous PCDD/Fs are dominant in flue gas
      at temperatures in the range 350-400 degrees C regardless of particle
      concentration.

PMID- 18054161
TI  - Suppressive effects of magnesium oxide materials on cadmium uptake and
      accumulation into rice grains II: Suppression of cadmium uptake and accumulation
      into rice grains due to application of magnesium oxide materials.
AB  - The objective of this study is to assess the applicability of a commercial
      magnesium oxide (MgO) and a composite material containing MgO and natural
      minerals ('MgO-SH-A') as the soil amendments for suppression of cadmium (Cd)
      uptake and accumulation into rice grains. A cultivation experiment of rice plants
      (Oryza sativa L. cv. Kinuhikari) was conducted in an actual Cd-contaminated
      alluvial paddy field to evaluate the effectiveness of these materials. The 'plant
      available' fractions of Cd in the paddy soil significantly decreased by
      application of commercial MgO at 2250 kg ha(-1) or MgO-SH-A at 4500 kg ha(-1).
      These decreases would be primarily attributed to the increase in soil pH due to
      applications of the MgO materials because these soil Cd fractions were
      significantly negatively correlated with the soil pH. Even under a suppressive
      condition for Cd uptake by rice plants, i.e., continuous flooding of the paddy
      field around the heading stage, applications of these materials further reduced
      Cd concentration in brown rice as compared to that from the control. It was
      concluded that the two MgO materials examined would be effective in preventing Cd
      contamination of rice grains grown in Cd-polluted paddy fields.

PMID- 18054162
TI  - Catalytic oxidation of dichloromethane and toluene over platinum alumite
      catalyst.
AB  - Catalytic oxidation technology is one of the most promising technologies for the
      reduction of volatile organic compound (VOC) emissions. It is very necessary to
      study the catalytic oxidation of mixture of VOCs and volatile organic compounds
      (CVOCs), because VOCs are always emitted accompanying with CVOCs. Hence, the
      catalytic oxidation reaction of toluene and CH2Cl2 is explored on a platinum
      alumite catalyst in this work. The results show that the addition of toluene has
      no effect on the decomposition of CH2Cl2, although it can suppress CH3Cl
      formation because the steam generated from the catalytic combustion of toluene
      suppresses the formation of CH3Cl from CH2Cl2. High concentrations of CH2Cl2 have
      a negative effect on the catalytic combustion of toluene.

PMID- 18054163
TI  - Biological removal of cyanide compounds from electroplating wastewater (EPWW) by
      sequencing batch reactor (SBR) system.
AB  - Biological treatment system especially, sequencing batch reactor (SBR) system
      could not be applied to treat the raw electroplating wastewater (EPWW) due to the
      low organic matter concentration of 10+/-3 mg-BOD5/L and toxic of high cyanide
      concentration of 23.0+/-2.2 mg-CN/L. However, EPWW could be used as the nitrogen
      source for the bio-sludge of SBR system. And 10% of EPWW (the final cyanide
      concentration of 2.3+/-0.2 mg/L) was most suitable to supplement into the
      wastewater as the nitrogen source. SBR system showed the highest COD, BOD5, TKN
      and cyanide removal efficiencies of 79+/-2%, 85+/-3%, 49.0+/-2.1% and 97.7+/
      0.7%, respectively with 4-times diluted Thai-rice noodle wastewater (TRNWW)
      containing 10% EPWW and 138 mg/L NH4Cl (BOD5: TN of 100:10) at SRT of 72+/-13
      days (under organic and cyanide loadings of 0.40 kg-BOD5/m3 d and 0.0023 kg-CN/m3
      d, respectively). However, the effluent ammonia was still high of 22.6+/-0.4 mg
      N/L while the effluent nitrate and nitrite was only 9.9+/-0.4 and 1.2+/-0.9 mg
      N/L, respectively. And SVI and effluent SS of the system were higher than 95 and
      75 mg/L, respectively.

PMID- 18054164
TI  - Biosorption of aluminum on Pseudomonas aeruginosa loaded on Chromosorb 106 prior
      to its graphite furnace atomic absorption spectrometric determination.
AB  - A biosorption procedure for separation-enrichment of aluminum in environmental
      samples has been presented in this work. Pseudomonas aeruginosa loaded on
      Chromosorb 106 has been used as biosorbent for that purpose. P. aeruginosa is a
      gram-negative, aerobic rod. The influences of pH of the aqueous solution, eluent
      type, eluent volume, sample volume, etc. were examined on the quantitative
      recovery of aluminum in P. aeruginosa loaded on Chromosorb 106. The effects of
      concomitant ions on the recoveries of aluminum were also investigated. The
      detection limit based on 3 sigma for aluminum is 30 ng L(-1). Three certified
      reference materials (LGC 6010 Hard Drinking Water, NIST-SRM 1568a Rice Flour and
      NRCC-DORM-2 Dogfish Muscle) were analyzed for the validation of the presented
      procedure. The proposed procedure was applied to the determination of aluminum in
      environmental samples including natural water and food samples. The concentration
      of aluminum in real samples was found at ppb level.

PMID- 18054165
TI  - Studies on the runaway reaction of ABS polymerization process.
AB  - Taiwan has the largest acrylonitrile-butadiene-styrene (ABS) copolymer production
      in the world. Preventing on unexpected exothermic reactions and related emergency
      relief hazard is essential in the safety control of ABS emulsion polymerization.
      A VSP2 (Vent Sizing Package 2) apparatus is capable of studying both normal and
      abnormal conditions (e.g., cooling failure, mischarge, etc.) of industrial
      process. In this study, the scenarios were verified from the following abnormal
      conditions: loss of cooling, double charge of initiator, overcharge of monomer,
      without charge of solvent, and external fire. An external fire with constant
      heating will promote higher self-heat rate and this is recommended as the worst
      case scenario of emulsion polymerization on butadiene. Cooling failure coupled
      with bulk system of reactant was determined to be the credible worst case in ABS
      emulsion polymerization. Finally, the emergency vent sizing based on
      thermokinetics from VSP associated with DIERS methodology were used for
      evaluating the vent sizing and compared to that of the industrial plants.

PMID- 18054166
TI  - Palladium-catalyzed hydrodehalogenation of 1,2,4,5-tetrachlorobenzene in water
      ethanol mixtures.
AB  - Palladium-catalyzed hydrodehalogenation (HDH) was applied for destroying 1,2,4,5
      tetrachlorobenzene (TeCB) in mixtures of water and ethanol. This investigation
      was performed as a critical step in the development of a new technology for clean
      up of soil contaminated by halogenated hydrophobic organic contaminants. The main
      goals of the investigation were to demonstrate the feasibility of the technology,
      to determine the effect of the solvent composition (water:ethanol ratio), and to
      develop a model for the kinetics of the dehalogenation process. All experiments
      were conducted in a batch reactor at ambient temperature under mild hydrogen
      pressure. The experimental results are all consistent with a Langmuir-Hinshelwood
      model for heterogeneous catalysis. Major findings that can be interpreted within
      the Langmuir-Hinshelwood framework include: (1) the rate of hydrodehalogenation
      depends strongly on the solvent composition, increasing as the water fraction of
      the solvent increases; (2) the HDH rate increases as the catalyst concentration
      in the reactor increases; (3) when enough catalyst is present, the HDH reaction
      appears to follow first-order kinetics, but the kinetics appear to be zero-order
      at low catalyst concentrations. TeCB is converted rapidly and quantitatively to
      benzene, with only trace concentrations of 1,2,4-trichlorobenzene appearing as a
      reactive intermediate. The results obtained here have important implications for
      the further development of the proposed soil remediation technology, and may also
      be important for the treatment of other hazardous waste streams.

PMID- 18054167
TI  - A novel "ghost"-free tomographic image reconstruction method applicable to rotary
      shadowed replica specimens.
AB  - Electron tomography by conventional filtered back-projection is often seriously
      impaired by anisotropic resolution due to unavoidable limitation in specimen tilt
      angles. We propose a new approach to overcome the problem for thin film-like
      replica-type specimens in which internal density is supposed as homogenous and
      contiguously distributed, by imposing a reasonable constraint of density-existing
      region in the reconstruction procedure. The objects were approximated as a
      distribution of binary voxels and the intensity of the projected images being
      proportional to the thickness along the projection ray. The new reconstruction
      algorithm consists of initial determination of approximate constraint region by a
      topographic analysis by stereo-photogrammetry, followed by iterative computation
      to find the unique solution of simultaneous equations, so that all the intensity
      distribution in tilt-series images are included within pre-determined voxel
      arrangement. During a trial run with a new methodology, we realized its
      significantly advantageous feature that much less number of projection images
      than conventional back-projection is required to perform the reconstruction of
      almost equivalent quality. Here, we show the performance of this novel algorithm
      by 3-D reconstruction of quick-freeze deep-etch replica specimens without any
      trace of spurious ghosting caused by missing-wedge problems.

PMID- 18054168
TI  - An electron microscope for the aberration-corrected era.
AB  - Improved resolution made possible by aberration correction has greatly increased
      the demands on the performance of all parts of high-end electron microscopes. In
      order to meet these demands, we have designed and built an entirely new scanning
      transmission electron microscope (STEM). The microscope includes a flexible
      illumination system that allows the properties of its probe to be changed on-the
      fly, a third-generation aberration corrector which corrects all geometric
      aberrations up to fifth order, an ultra-responsive yet stable five-axis sample
      stage, and a flexible configuration of optimized detectors. The microscope
      features many innovations, such as a modular column assembled from building
      blocks that can be stacked in almost any order, in situ storage and cleaning
      facilities for up to five samples, computer-controlled loading of samples into
      the column, and self-diagnosing electronics. The microscope construction is
      described, and examples of its capabilities are shown.

PMID- 18054169
TI  - Progress and perspectives for atomic-resolution electron microscopy.
AB  - The transmission electron microscope (TEM) has evolved into a highly
      sophisticated instrument that is ideally suited to the characterization of
      advanced materials. Atomic-level information is routinely accessible using both
      fixed-beam and scanning TEMs. This report briefly considers developments in the
      field of atomic-resolution electron microscopy. Recent activities include renewed
      attention to on-line microscope control ('autotuning'), and assessment and
      correction of aberrations. Aberration-corrected electron microscopy has developed
      rapidly in several forms although more work needs to be done to identify standard
      imaging conditions and to explore novel operating modes. Preparation of samples
      and image interpretation have also become more demanding. Ongoing problems
      include discrepancies between measured and simulated image contrast, concerns
      about radiation damage, and inversion of electron scattering.

PMID- 18054170
TI  - Seeing atoms with aberration-corrected sub-Angstrom electron microscopy.
AB  - High-resolution electron microscopy is able to provide atomic-level
      characterization of many materials in low-index orientations. To achieve the same
      level of characterization in more complex orientations requires that instrumental
      resolution be improved to values corresponding to the sub-Angstrom separations of
      atom positions projected into these orientations. Sub-Angstrom resolution in the
      high-resolution transmission electron microscope has been achieved in the last
      few years by software aberration correction, electron holography, and hardware
      aberration correction; the so-called "one-Angstrom barrier" has been left behind.
      Aberration correction of the objective lens currently allows atomic-resolution
      imaging at the sub-0.8A level and is advancing towards resolutions in the deep
      sub-Angstrom range (near 0.5A). At current resolution levels, images with sub
      Rayleigh resolution require calibration in order to pinpoint atom positions
      correctly. As resolution levels approach the "sizes" of atoms, the atoms
      themselves will produce a limit to resolution, no matter how much the
      instrumental resolution is improved. By arranging imaging conditions suitably,
      each atom peak in the image can be narrower, so atoms are imaged smaller and may
      be resolved at finer separations.

PMID- 18054171
TI  - Biotransformation of flubendazole and selected model xenobiotics in Haemonchus
      contortus.
AB  - Haemonchus contortus is one of the most pathogenic parasites of small ruminants
      (e.g., sheep and goat). The treatment of haemonchosis is complicated because of
      frequent resistance of H. contortus to common anthelmintics. The development of
      resistance can be facilitated by the action of drug metabolizing enzymes of
      parasites that can deactivate anthelmintics and thus protect parasites against
      the toxic effect of the drug. The aim of this project was to investigate the
      Phase I biotransformation of benzimidazole anthelmintic flubendazole in H.
      contortus and to determine the biotransformation of other model xenobiotics. For
      this purpose, in vitro (subcellular fractions of H. contortus homogenate) as well
      as ex vivo (live nematodes cultivated in flasks with medium) experiments were
      used. The results showed that cytosolic NADPH-dependent enzymes of H. contortus
      metabolize flubendazole via reduction of its carbonyl group. The apparent kinetic
      parameters of this reaction were determined (V'max=39.8+/-2.1 nM min(-1),
      K'm=1.5+/-0.3 microM). The reduction of flubendazole in H. contortus is
      stereospecific, the ratio of (-):(+) enantiomers of reduced flubendazole formed
      was 90:10. Reduced flubendazole was the only Phase I metabolite found. Effective
      reduction of other xenobiotics with carbonyl group (metyrapon, daunorubicin, and
      oracin) was also found. Significant activity of carbonyl-reducing enzymes may be
      important for H. contortus to survive the attacks of anthelmintics or other
      xenobiotics with carbonyl group.

PMID- 18054172
TI  - First aid and initial management for childhood burns in Vietnam--an appeal for
      public and continuing medical education.
AB  - A prospective study to investigate first aid and initial management for 247
      paediatric burn patients from 1 June, 2004 to 31 June, 2006 at the Burn Intensive
      Care Unit, National Institute of Burns (NIB), Hanoi. Data were collected from
      documents from referring hospitals and direct interview of patients, relative and
      transport team as guided by the International Society for Burn Injury (ISBI) and
      the World Health Organization (WHO). Results showed that cooling the burn surface
      by cold water was applied in 27.17%. Among 132 patients transferred from other
      hospitals, fluid resuscitation was given in 102 patients (77.28%) before
      transferring and over a half of these patients were not given intravenous fluid
      during the time of transfer, especially for children under 1 year of age
      (p<0.05). Dressings were applied in 36.36% of transferred patients. Burn surface
      area was accurately diagnosed in only 21.90% of total cases. In conclusion, first
      aid and initial management in Vietnam are still far from ideal. Further public
      education and continuing medical education should be applied in Vietnam.

PMID- 18054173
TI  - Three-dimensional probabilistic maps of the occipital sulci of the human brain in
      standardized stereotaxic space.
AB  - Developments in functional neuroimaging in normal human subjects, such as
      functional magnetic resonance imaging (fMRI), have permitted the mapping of
      several visual areas of the human brain and have already provided provisional
      identification of some of the visual areas that were first described in nonhuman
      primates. However, the lack of a detailed description of the sulcal patterns of
      the human occipital lobe makes it difficult to establish clear relationships
      between sulcal landmarks and identified visual areas with functional
      neuroimaging. In the present study we used magnetic resonance images to
      investigate the morphological variation of the human occipital sulci in both the
      left and right hemispheres of 40 normal adult human brains. We identified 11
      occipital sulci, the parieto-occipital fissure and the temporo-occipital
      incisure, and their corresponding gray matter voxels were marked in the magnetic
      resonance volumes which had been transformed into the Montreal Neurological
      Institute standard proportional stereotaxic space. Probability maps were then
      constructed for each occipital sulcus. These probability maps provide a
      quantitative measure of the variability of the occipital sulci in standard
      stereotaxic space and are a useful tool to identify the location of voxels of
      other magnetic resonance imaging images transformed in the same stereotaxic
      space.

PMID- 18054174
TI  - Metacognitive beliefs about alcohol use: development and validation of two self
      report scales.
AB  - The goal of this research was to develop clinical assessment tools of positive
      and negative metacognitive beliefs about alcohol use. In Study 1 we constructed
      two scales and conducted preliminary factor analyses. Studies 2 and 3
      investigated the predictive validity and temporal stability of the scales. Study
      4 examined the factor structure, predictive validity and classification accuracy
      of the scales in a clinical sample. The Positive Alcohol Metacognitions Scale
      (PAMS) and the Negative Alcohol Metacognitions Scale (NAMS) were shown to possess
      good psychometric properties, as well as predictive validity and classification
      accuracy, in both clinical and community populations. The scales may aid future
      research into problem drinking and facilitate clinical assessment and case
      formulation.

PMID- 18054175
TI  - [Latest developments: management and treatment of preeclampsia].
AB  - Preeclampsia is defined as the association of pregnancy-induced hypertension and
      proteinuria of 300 mg/24h or more after 20 weeks gestation. It complicates 0.5 to
      7% of pregnancies. It is a severe complication of pregnancy, which leads to
      persisting fetal morbidity and mortality. It is also responsible for maternal
      morbidity as placental abruption, HELLP syndrome (hemolysis, elevated liver
      enzymes, low platelets) and eclampsia. Without treatment, maternal risks are
      high. Once the disease is confirmed, the treatment consists of ending the
      pregnancy. Corticosteroids for lung maturity have to be prioritized depending on
      the term. Antihypertensive drugs are used to limit maternal complications, in
      particular, in neurological form. Calcium pump inhibitors are increasingly used
      as a first line choice. Magnesium sulfate, which is probably not used enough in
      France, needs to be administered with care and strict monitoring. It can be used
      to prevent a recurrence of eclamptic fits or in the context of early severe
      preeclampsia with neurological irritability where an eclamptic fit seems
      imminent. Preventive treatment of preeclampsia consists essentially of low dose
      aspirin. The efficacy of this treatment is real but moderate. It decreases the
      risk of recurrence of preeclampsia by 10 to 15%, of prematurity by 8% and of
      perinatal mortality by 14%. These figures were recently corrected to 10% for the
      risk of recurrence of preeclampsia: RR=0.95; 90% CI; (0.84-0.97) and prematurity:
      RR=0.95; 90%CI; (0.83-0.98). It seems that it has no significant effect on intra
      uterine growth restriction (IUGR) and perinatal death prevention. For the main
      outcome of preeclampsia, there was no evidence that women in any of subgroups as
      preexisting renal disease, preexisting diabetes or hypertension benefited more or
      less from the use of antiplatelet agents than those in any other subgroup.

PMID- 18054176
TI  - Gene tagging and gene replacement using recombinase-mediated cassette exchange in
      Schizosaccharomyces pombe.
AB  - Cre/lox site-specific recombination systems provide important tools for genetic
      manipulation. Here we present an efficient method for gene tagging and gene
      replacement using Cre recombinase-mediated cassette exchange (RMCE). The cassette
      consists of the S. pombe ura4(+) selectable marker flanked by a wild-type loxP
      site at one end and by a modified heterospecific lox site (loxM3) at the other.
      The cassette is stable because the flanking lox sites cannot recombine with each
      other. Following integration of the cassette at the chosen chromosomal locus,
      exchange is achieved by introducing a Cre-expression plasmid containing an
      equivalent cassette containing the required tag or gene sequence. Recombinants
      are selected by uracil prototrophy using the reagent 5-fluoroorotic acid (5-FOA).
      The cassette exchange system provides for repetitive integrations at the same
      locus, allowing different protein tags or gene sequences to be integrated quickly
      and efficiently. We have established a range of reagents and verified utility by
      C-terminally tagging the S. pombe rad4 and swi1 genes with yEGFP and the yEGFP
      derivatives yECFP and yECitrine and by transferring the coding sequence for both
      genes.

PMID- 18054177
TI  - Increasing genomic information in bivalves through new EST collections in four
      species: development of new genetic markers for environmental studies and genome
      evolution.
AB  - The generation of EST information is an essential step in the genomic
      characterisation of species. In the context of the European Network Marine
      Genomics, a common goal was to significantly increase the amount of ESTs in
      commercial marine mollusk species and more specifically in the less studied but
      ecologically and commercially important groups, such as mussel and clam genera.
      Normalized cDNA libraries were constructed for four different relevant bivalves
      species (Crassostrea gigas, Mytilus edulis, Ruditapes decussatus and
      Bathymodiolus azoricus), using numerous tissues and physiological conditions. In
      this paper, we present the analysis of the 13,013 expressed sequence tags (ESTs)
      generated. Each EST library was independently assembled and 1300-3000 unique
      sequences were identified in each species. For the different species, functional
      categories could be assigned to only about 16 to 27% of ESTs using the GO
      annotation tool. All sequences have been incorporated into a publicly available
      database and form the basis for subsequent microarray design, SNP detection and
      polymorphism analysis, and the placement of novel markers on genetic linkage
      maps.

PMID- 18054178
TI  - Performance of a whole blood interferon-gamma assay for detection and eradication
      of caseous lymphadenitis in sheep.
AB  - Caseous lymphadenitis (CLA), a chronic bacterial disease of sheep and goats
      caused by Corynebacterium pseudotuberculosis, could be controlled by eradication
      of infected carriers. This study aimed at validation of a whole blood interferon
      gamma (IFN-gamma) enzyme immunoassay (EIA) (Bovigam, Pfizer) in naturally
      infected sheep for use in eradication of infection from a flock. This assay used
      formalin-inactivated whole bacterial cells as antigen. The sensitivity of the
      whole cell assay was improved by increasing both the volume of blood and the
      number of bacterial cells. The assay was validated in experimentally infected
      sheep and in a flock of known-negative sheep, as well as in a naturally infected
      flock, a proportion of which was vaccinated with a commercial CLA vaccine. An
      optical density (540nm) (OD) cut-off of 0.09 was effective in classifying animals
      as test positive or negative in the naturally infected flock, although there was
      variation in OD between visits, notably with weakly reacting animals. The test
      had a sensitivity of 91% and a specificity of 98%. Postmortem data supported the
      results in test-negative animals. Visit-to-visit variation in IFN-gamma EIA OD in
      the naturally infected flock as well as CLA disease status was used to develop an
      algorithm for the eradication of CLA from a known infected flock. The whole blood
      IFN-gamma assay shows promise for eradication of caseous lymphadenitis from sheep
      flocks.

PMID- 18054179
TI  - Antimicrobial resistance in Salmonella enterica serovar Typhimurium from human
      and animal sources in Italy.
AB  - Salmonella Typhimurium strains isolated in Italy in the period 2002-2004 from
      human and animal sources were examined for their antimicrobial susceptibility.
      Resistance to tetracycline (T, 73.6%), sulfonamides (Su, 73.3%), ampicillin (A,
      67.6%), streptomycin (S, 65.4%) and chloramphenicol (C, 32.3%) were frequently
      observed. Resistance to ciprofloxacin was only observed in a swine strain, but
      most human strains resistant to nalidixic acid showed reduced susceptibility to
      that drug (MIC > or = 0.125 mg/l). Overall, 64% of the strains were resistant to
      four or more drugs. The most common resistance profiles were ACSSuT, prevalent in
      strains belonging phage type DT104 and ASSuT, prevalently associated with strains
      unable to be typed.

PMID- 18054180
TI  - Alteration of saliva and serum concentrations of manganese, copper, zinc, cadmium
      and lead among career welders.
AB  - Human saliva offers a unique noninvasive approach for populational study.
      Purposes of this study were to investigate the feasibility of using saliva
      manganese (Mn) concentration as a biomarker of Mn exposure among career welders
      and to study the variations of Mn, copper (Cu), zinc (Zn), cadmium (Cd), and lead
      (Pb) in saliva as affected by the welding profession. Forty-nine male welders, of
      whom 28 were in the low exposed group and 21 in the high exposed group, were
      recruited. Control subjects were 33 military soldiers without metal exposure.
      Ambient Mn levels in breathing zones were 0.01, 0.24 and 2.21mg/m(3) for control,
      low, and high exposed groups, respectively. Saliva samples were collected to
      quantify metals by inductive coupled plasma mass spectrometer (ICP-MS). Saliva
      concentrations of Mn and Cu were significantly higher in welders than in controls
      (p<0.01); the variation in saliva levels appeared likely to be associated with
      airborne Mn levels among study populations. Saliva levels of Zn were
      significantly lower in welders than in controls (p<0.05), while Cd and Pb levels
      in saliva were unchanged. Significant associations were observed between saliva
      and serum for Mn (r=0.575, p<0.05) and Cu (r=0.50, p<0.05). Moreover, saliva Mn
      concentrations were higher among welders with 5-10years of employment than those
      with less than 5years of employment. Linear regression analysis revealed a
      significant correlation between saliva Mn and Cu and between saliva Mn and Zn.
      Taken together, these data suggest that Mn concentrations in saliva appear
      reflective of welders' exposure to airborne Mn and their years of welding
      experience, respectively. Elevated Mn levels among welders may alter the
      homeostasis of Cu and Zn.

PMID- 18054181
TI  - Method for screening of solid dispersion formulations of low-solubility compounds
      -miniaturization and automation of solvent casting and dissolution testing.
AB  - An efficient method has been developed for screening solid dispersion
      formulations that are intended to enhance the dissolution of poorly soluble
      compounds. The method is based on miniaturization and automation of sample
      preparation by solvent casting, and dissolution testing, in a 96-well plate
      format, using less than 0.1mg of compound per well. To illustrate the method, six
      polymers and eight surfactants were screened, individually and in combination,
      for their ability to dissolve a compound with aqueous solubility of < 1 microg/ml
      in simulated intestinal fluid. Screening was performed at an excipient/compound
      ratio of 10:1, and a polymer/surfactant ratio of 3:1 for ternary formulations.
      Sixteen of the 48 ternary formulations dissolved the compound to a level > 100
      microg/ml, i.e. at least a 100-fold increase over the aqueous solubility. A
      number of synergies were observed wherein the performance of a ternary
      formulation greatly exceeded that of either of the corresponding binary
      formulations. Thirteen 'hits' from screening were scaled up with melt methods,
      and approximately 2/3 of these showed comparable dissolution enhancement when
      tested at larger scale. Five of these were administered to rats, and the absolute
      oral bioavailability ranged from 10 to 23%, versus less than 1% for the
      unformulated compound.

PMID- 18054182
TI  - Injectable actarit-loaded solid lipid nanoparticles as passive targeting
      therapeutic agents for rheumatoid arthritis.
AB  - This work systematically studied the intravenous injection formulation of solid
      lipid nanoparticles (SLNs) loaded with actarit, a poor water soluble anti
      rheumatic drug. The goal of this study was to design passive targeting
      nanoparticles which could improve therapeutic efficacy and reduce side-effects
      such as nephrotoxicity and gastrointestinal disorders commonly associated with
      oral formulations of actarit. Based on the optimized results of single-factor and
      orthogonal design, actarit-loaded SLNs were prepared by a modified solvent
      diffusion-evaporation method. The formulated SLNs were found to be relatively
      uniform in size (241+/-23 nm) with a negative zeta potential (-17.14+/-1.6 mV).
      The average drug entrapment efficiency and loading were (50.87+/-0.25)% and
      (8.48+/-0.14)%, respectively. The actarit-loaded SLNs exhibited a longer mean
      retention time in vivo (t(1/2(beta)), 9.373 h; MRT, 13.53 h) compared with the
      actarit 50% propylene glycol solution (t(1/2(ke)), 0.917 h; MRT, 1.323 h) after
      intravenous injection to New Zealand rabbits. The area under curve of plasma
      concentration-time (AUC) of actarit-loaded SLNs was 1.88 times greater than that
      of the actarit in 50% propylene glycol solution. The overall targeting efficiency
      (TE(C)) of the actarit-loaded SLNs was enhanced from 6.31% to 16.29% in spleen
      while the renal distribution of actarit was significantly reduced as compared to
      that of the actarit solution after intravenous administration to mice. These
      results indicated that injectable actarit-loaded solid lipid nanoparticles were
      promising passive targeting therapeutic agents for rheumatoid arthritis.

PMID- 18054183
TI  - Screening of biochemical modulator by tumor cell permeability of doxorubicin.
AB  - We screened various food components for their ability to inhibit doxorubicin
      (DOX) permeability in tumor cells in vitro with the aim of finding novel
      modulators. Capsaicin did not change DOX permeability in the tumor cells,
      although the capsaicin derivatives gingerol and ferulic acid tended to promote
      DOX efflux. Combinations of these components with DOX were also not effective. In
      contrast, cucurbitacin E significantly promoted DOX influx into tumor cells and
      increased DOX concentration in tumor cells. Furthermore, combined cucurbitacin E
      significantly suppressed DOX efflux from tumor cells and was shown to maintain
      the DOX level in tumor cells. It was also confirmed that the combination of
      cucurbitacin E with DOX resulted in effective cytotoxicity for tumor cells in
      culture. Additionally, the combination of cucurbitacin E and DOX showed increased
      cytotoxicity when compared to each treatment alone. In vivo, DOX alone treatment
      did not change the time course of tumor size or tumor weight of M5076 ovarian
      sarcoma, compared to control levels. In contrast, the combination of cucurbitacin
      E with DOX resulted in decreased tumor size and tumor weight, compared to that in
      DOX alone group, indicating effective antitumor activity. In conclusion, the
      combination of cucurbitacin E with DOX may be an effective tool with treated
      application in the cancer chemotherapy.

PMID- 18054184
TI  - Evaluation of poly(styrene-alt-maleic anhydride)-ethanol as enteric coating
      material.
AB  - This study aims at evaluating the potential of SMA-ethanol as enteric coating
      polymer for erythromycin tablets. SMA-ethanol was synthesized and characterized
      for physicochemical properties, molecular weight and thermal analysis. Free films
      were prepared by adding different kinds and amounts of plasticizers, the film
      surface topography was determined by a SEM, the tensile strength, water vapor
      transmission rate and moisture absorption were also tested to choose the most
      promising film. DBP was proved to be the most suitable plasticizer with a best
      using amount of 20%, such polymer films had low vapor transmission rate and low
      moisture absorption which were very important to an enteric coating material. The
      polymer was further characterized for film coating by evaluating the release of
      erythromycin tablets in vitro, tablets coated with SMA-ethanol can satisfy the
      drug release requests of USP when the film weight gains were between 4 and 6%;
      tablets coated with both a subcoat and the polymer showed excellent gastro
      resistance, less than 0.2% drug release occurred even with weight gains as less
      as 2% after 2h exposure to acid (pH 1), while over 90% drug release occurred in
      pH 6.8 sodium phosphate buffer within 45 min, regardless of weight gains of
      coating material, moreover, we confirmed that the application of a subcoat could
      decrease the amount of required coating polymer. In conclusion, the potential use
      of SMA-ethanol as enteric coating material was demonstrated.

PMID- 18054185
TI  - Pingyangmycin loaded bovine serum albumin microspheres for chemoembolization
      therapy--in vitro and in vivo studies.
AB  - Chemoembolization based on microspheres have been emerged as a novel and
      promising way for interventional therapy, however, the exact effect and probable
      mechanism have not been revealed. The purpose of our study was to evaluate the
      potential of Pingyangmycin loaded bovine serum albumin microspheres (PYM-BSA-MSs)
      for chemoembolization therapy both in vitro and in vivo. The effect of PYM-BSA
      MSs on cell growth curves and changes of cell morphology and activities measured
      by MTT assay were carried out in human umbilical vein endothelial ECV-304 cells.
      The in vivo occlusion effect was evaluated in 24 healthy rabbits. Macroscopic
      examinations and Hematoxylin-Eosin (H-E) staining of cross-section of rabbits'
      central auricular arteries were employed to observe the apparent and histological
      changes of arterioles. The results show that the PYM-BSA-MSs could inhibit the
      proliferation and induce the apoptosis of ECV-304 cells in a time-dependent
      manner. In vivo studies demonstrated that 21 days after artery embolization with
      the PYM-BSA-MSs, neointimal thickening of arterioles and significant hyperplasia
      of endothelial cells could be detected, but without completely interruption of
      blood flow. Compared with plain PYM aqueous solution or BSA-MSs oily suspension,
      PYM-BSA-MSs showed excellent potential as an alternative to interventional
      embolization materials.

PMID- 18054186
TI  - Evaluation of the analgesic effect of alkaloid extract of Peganum harmala L.:
      possible mechanisms involved.
AB  - The seeds of Peganum harmala L. (Pgh) (Zygophyllaceae) have been used in Moroccan
      traditional medicine for treatment of a various diseases and to relieve dolorous
      process. The major objective of this paper was to investigate the mechanism of
      the analgesia induced by alkaloid extract of Peganum harmala. In the present
      work, the antinociceptive action was assayed in several experimental models in
      mice: writhing, formalin, and hot plate tests. The alkaloid extract (12.5 and
      25mg/kg) and in a dose-dependent manner significantly reduced the nociception by
      acetic acid intraperitoneal injection (p<0.001). In the formalin test, the
      extract also significantly reduced the painful stimulus in both phases of the
      test (p<0.001). Treatment with the extract when given by (i.p. or i.c.v.) or with
      morphine (10mg/kg, i.p.) produced a significant increase of the reaction time in
      hot plate test. These result showed that the alkaloid extract of Pgh contains
      active analgesic principles acting both centrally and peripherally. Furthermore,
      this antinociceptive effect has been avoided by naloxone at a dose of 1mg/kg in
      the first phase of formalin and hot plate tests indicating that this extract act
      partly through an opioid-mediated mechanism. In conclusion, the alkaloid extract
      of Peganum harmala seems to have both central and peripheral antinociceptive
      activities which may be mediated by opioid receptors.

PMID- 18054187
TI  - [The participation of primary care physicians in integrated health services
      network: United States experiences].
AB  - BACKGROUND: Reforms of care and services have affected primary care physicians,
      but very little attention has been devoted to their actual participation in
      Integrated Health Services Network (IHSN). METHODS: From a literature review of
      articles published from January 1985 to December 2006, we selected 24 studies on
      physicians' participation in IHSN and their perceptions on practices. RESULTS:
      This literature review suggests that physicians' perceptions of IHSN are linked
      to their actual level of participation. Physicians who participated fully
      perceived improvements in all practice dimensions. Physicians who participated
      partially were dissatisfied with physician-patient relationships, perceived a
      loss of professional autonomy and increased gate-keeping constraints. They had
      however a positive perception of the overall quality of care. When physicians
      received capitation payments, they were overall dissatisfied. CONCLUSIONS: In
      order to improve primary care physicians' participation in IHSN, quality of care
      should be reinforced, capitation payment avoided and gate-keeping should be
      transformed into coordination of care.

PMID- 18054188
TI  - [A case of Nasal septum abscess].
AB  - INTRODUCTION: Abscess of the nasal septum is a rare and serious infection,
      because of the complications which it can generate. The authors report a new case
      of nasal septum abscess probably of dental origin. OBSERVATION: A 47-year-old man
      consulted for bilateral nasal obstruction and rhinorrhea for 3 days with fever.
      The clinical examination as well as TDM imagery revealed a septal abscess. The
      patient underwent surgical drainage associated to triple antibiotherapy, with a
      good evolution at the end of 10 days. The etiologic assessment suggested dental
      infection. CONCLUSION: This is a rare and serious infection of the nasal septum.
      This new case of rare abscess of the nasal septum gives us the opportunity to
      describe out the various etiologies, their management, and to insist on the
      preventive treatment of this infection.

PMID- 18054189
TI  - [Cardiotoxicity of n-methyl-glucamine antimoniate (Glucantime). A case report].
AB  - The pentavalent antimonial meglumine (Glucantime) is the drug of choice in
      treatment of cutaneous leishmaniasis in Tunisia. It may create severe adverse
      effects. A ten year-old girl was treated by Glucantime for cutaneous
      leishmaniasis. On the eighth day of treatment, she developed palpitations and
      precordialgia. The ECG showed T wave inversion prolongation of corrected QT
      interval. Drug therapy was stopped. Within a few days, she recovered and her
      elctrocardiographic changes came back to normal. The cardio toxicity of
      Glucantime may be severe. Electrocardiographic changes are the primary signs.
      Long term ECG follow-up is necessary.

PMID- 18054190
TI  - Clinical, immunological, anti-inflammatory and antioxidant roles of zinc.
AB  - The essentiality of zinc for humans was recognized only 40 years ago. Zinc
      deficiency was suspected to occur in Iranian patients with growth retardation,
      hypogonadism in males, hepato-splenomegaly, rough and dry skin, geophagia and
      severe iron deficiency anemia. Later we documented zinc deficiency in similar
      patients in Egypt. The diet of these patients consisted of mainly cereal proteins
      which contained high phytate and this led to decreased availability of iron and
      zinc. These patients had severe immune dysfunctions, inasmuch as they died of
      intercurrent infections by the time they were 25 years of age. In our studies in
      experimental human model of zinc deficiency, we documented decreased serum
      testosterone level, oligospermia, severe immune dysfunctions mainly affecting T
      helper cells, decreased serum thymulin activity hyperammonemia, neuro-sensory
      disorders and decreased lean body mass. The basic mechanisms of zinc action on
      immune cells have been reviewed in this paper. Our studies showed that the
      activation of many zinc dependent enzymes and transcription factors were affected
      adversely due to zinc deficiency. The gene expression and production of Th1
      cytokines were affected adversely due to zinc deficiency. Zinc is also an
      antioxidant and has anti-inflammatory actions. We have reported decreased plasma
      zinc, increased plasma oxidative stress markers and increased generation of
      inflammatory cytokines in the elderly subjects which were corrected by zinc
      supplementation. In cell culture studies, we have observed that zinc induces A20
      which inhibits NF-kappaB activation resulting in decreased generation of
      inflammatory cytokines.

PMID- 18054191
TI  - Does age influence loss of heterozygosity?
AB  - The striking correlation between advanced age and an increased incidence of
      cancer has led investigators to examine the influence of aging on genome
      maintenance. Because loss of heterozygosity (LOH) can lead to the inactivation of
      tumor suppressor genes, and thus carcinogenesis, understanding the affect of
      aging on this type of mutation event is particularly important. Several factors
      may affect the rate of LOH, including an increase in the amount of DNA damage,
      specifically double-strand breaks (DSBs), and the ability to efficiently repair
      this damage via pathways that minimize the loss of genetic information. Because
      of experimental constraints, there is only suggestive evidence for a change in
      the rate of DNA damage as humans age. However, recent studies in model organisms
      find that there are increased rates of LOH with age, and that repair of DNA
      damage occurs via a different pathway in old cells versus young cells. We
      speculate that the age-dependent change in DNA repair may explain why there is
      increased LOH, and that the findings from these model organisms may extend to
      humans.

PMID- 18054192
TI  - Zinc supplementation in the elderly subjects: effect on oxidized protein
      degradation and repair systems in peripheral blood lymphocytes.
AB  - Aging has been associated with zinc deficiency, leading to chronic inflammation
      and subsequent oxidative stress, especially in the immune system. The increased
      oxidative stress provokes the accumulation of oxidized proteins, raising the
      problem of the efficacy of intracellular protein maintenance systems responsible
      for the elimination of oxidatively modified proteins. Our objective was to
      analyse the effect of zinc supplementation in the elderly on protein maintenance
      in peripheral blood lymphocytes. The status of the proteasome, which is in charge
      of oxidized protein degradation and the repair enzymes peptide methionine
      sulfoxide reductases, which can reverse methionine oxidation in proteins, were
      analysed on peripheral blood lymphocytes collected from 20 elderly subjects (age
      range between 59 and 85 years old) before and after zinc supplementation (10mg of
      zinc per day for 48+/-2 days). A decrease of oxidized protein content in zinc
      supplemented subjects was observed and was associated with an increase of
      expression levels and/or activities of proteasome and methionine sulfoxide
      reductases. Our results indicate that zinc treatment could enhance the anti
      oxidative defences of peripheral blood lymphocytes by increasing the activities
      of protein maintenance systems responsible for the elimination of oxidatively
      modified proteins.

PMID- 18054193
TI  - Evolving insight into the role of mitochondrial DNA mutations in aging.
AB  - Mitochondria have occupied a central place in theories on the underlying cellular
      mechanisms of eukaryotic aging for several decades and much debate has ensued
      regarding the role of oxidative stress and mitochondrial genomic damage in these
      processes. Mouse models with greatly enhanced mitochondrial mutagenesis have
      produced dramatic aging-like phenotypes but recent results have led some to
      reassess whether such models are relevant to naturally occurring aging
      mechanisms. Here, we discuss the evolving insight that may be gained from these
      models regarding the contribution of mitochondrial DNA mutations to aging.

PMID- 18054194
TI  - Detection of counterfeit Viagra with Raman spectroscopy.
AB  - During the last few years, counterfeiters have become increasingly sophisticated
      by falsifying drugs and making them look identical to genuine tablets. In this
      paper, Raman spectroscopy is proposed as a fast and reliable method for the
      detection of counterfeit Viagra tablets. This technique can easily differentiate
      genuine from counterfeit tablets without the need of sample preparation. In total
      18 tablets were analysed which all contained the active ingredient sildenafil,
      but different excipients were used, as could be observed in the Raman spectra
      between 1150 and 700 cm(-1). So, the spectra could be divided into genuine or
      counterfeit. Additionally, principal component analysis (PCA), combined with
      hierarchical cluster analysis (HCA), was used to establish an automated approach
      for the discrimination of counterfeit from genuine Viagra tablets. Raman
      spectroscopy, combined with principal components analysis, could be used in the
      future by customs or in the field to identify counterfeit tablets on the spot
      without involvement of trained chemists.

PMID- 18054195
TI  - Analysis of CoQ10 in rat serum by ultra-performance liquid chromatography mass
      spectrometry after oral administration.
AB  - A UPLC-MS method for determining Coenzyme Q(10) (CoQ(10)) levels in rat serum was
      developed. CoQ(10) was quantitatively extracted into 2-propanol using a fast
      extraction procedure. The separation of CoQ(10) was performed on a Waters Acquity
      UPLCtrade mark BEH C(18) column (1.7 microm, 1.0 mm x 50 mm) with the mobile
      phase containing acetonitrile, 2-propanol, and formic acid (90:10:0.1) over 5
      min. The sensitivity of this method allows for the quantitation of 50 ng/mL
      CoQ(10) in serum (S/N=10). The linearity of this method was found to be from 50
      to 20,000 ng/mL. The precision was less than 10% (intra- and inter-day), and the
      average extraction recovery was between 90 and 105%. This procedure provides a
      precise, sensitive and direct assay method for the determination of CoQ(10) in
      rat serum after oral administration. This method could be applied to further
      pharmacokinetic studies of CoQ(10).

PMID- 18054196
TI  - Insulin regulates the expression of adiponectin and adiponectin receptors in
      porcine adipocytes.
AB  - Adiponectin is an adipocyte-derived hormone that can improve insulin sensitivity.
      Its functions in regulating glucose utilization and fatty acid metabolism in
      mammals are mediated by two subtypes of adiponectin receptors (AdipoR1 and
      AdipoR2). This study was conducted to determine the effect of insulin on the
      expression of adiponectin and its receptors. We demonstrated that in the presence
      of 10 nM insulin, addition of 1 microM of insulin or rosiglitazone (a peroxisome
      proliferator-activated receptor gamma (PPARgamma) agonist) had no effect on the
      expression of adiponectin and AdipoR genes in differentiated porcine adipocytes.
      However, the addition of 1 microM insulin plus 1 microM rosiglitazone
      significantly increased the AdipoR2 mRNA in differentiated porcine adipocytes.
      Using the phosphatidylinositol 3-kinase inhibitor (PI3K inhibitor, LY 294002), we
      found that insulin inhibited the expression of AdipoR2 through the PI3K pathway
      and this inhibition was blocked by addition of rosiglitazone. When porcine
      adipocytes were cultured without insulin, supplementation with 10 nM insulin
      inhibited the expression of AdipoR2 and this inhibition effect was also blocked
      by addition of rosiglitazone. Therefore, these data suggest that a PPARgamma
      agonist increases expression of AdipoR2 and that insulin inhibits the expression
      of AdipoR2 through the PI3K pathway.

PMID- 18054197
TI  - Caspases-3, -8, and -9 are required for induction of epithelial cell apoptosis by
      enteropathogenic E. coli but are dispensable for increased paracellular
      permeability.
AB  - Enteropathogenic Escherichia coli (EPEC) is an important cause of diarrhea,
      particularly among infants in developing countries. An increase in intestinal
      permeability due to EPEC infection has been suggested as a factor in the
      development of diarrhea. Abnormally high levels of programmed cell death
      (apoptosis) of intestinal epithelial cells can lead to increased intestinal
      permeability. The effects of EPEC on cell apoptosis remain incompletely
      understood. This study characterized the mechanisms of EPEC-induced epithelial
      apoptosis and examined whether this effect contributes to heightened permeability
      in an in vitro model of infection. We report that EPEC-induced apoptosis in T84
      intestinal epithelial cells via a mechanism involving caspases-3, -6, -8, and -9,
      the cleavage of PARP, and oligonucleosome formation. In addition, EPEC time
      dependently increased paracellular permeability as assessed by transepithelial
      resistance and the apical-to-basolateral movement of 3000 MW dextran.
      Furthermore, EPEC infection led to the cleavage and mislocalization of tight
      junctional ZO-1 and occludin. However, pharmacological inhibition of caspases did
      not prevent the EPEC-induced disruptions in epithelial barrier structure and
      function. Taken together, these results suggest that a caspase-dependent
      upregulation in epithelial cell apoptosis during EPEC infection occurs
      independent of impaired intestinal barrier function.

PMID- 18054198
TI  - Effects of depressive and anxious symptoms on norepinephrine and platelet P
      selectin responses to acute psychological stress among elderly caregivers.
AB  - BACKGROUND: Caring for a spouse with Alzheimer's disease is associated with
      increased psychological distress, impaired immunity, and heightened
      cardiovascular risk. Hyperreactivity of sympathetic and platelet activation
      responses to acute psychological stress, or the failure to recover quickly from
      stressful events, may constitute an important pathway linking stress and negative
      affect with cardiovascular disease (CVD). OBJECTIVES: (1) To evaluate
      associations between negative affect (i.e., depressive and anxious symptoms) with
      increased norepinephrine and P-selectin responses to an acute psychological
      stress task. (2) To establish whether these associations are augmented among
      elderly spousal caregivers (CG) compared to non-caregivers (NC). METHODS:
      Depressive (DEP) and anxious (ANX) symptoms from the Brief Symptom Inventory were
      assessed among 39 CG and 31 NC. Plasma norepinephrine levels (NE) and percent
      platelet P-selectin (PSEL) expression were assayed at three time-points: rest,
      immediately following a laboratory speech test (reactivity), and after 14 min of
      recovery. RESULTS: Among CG, but not NC, increased symptoms of depression and
      anxiety were associated with delayed NE recovery (DEP: beta=.460, p=.008; ANX:
      beta=.361, p=.034), increased PSEL reactivity (DEP: beta=.703, p<.001; ANX:
      beta=.526, p=.002), and delayed PSEL recovery (DEP: beta=.372, p=.039; ANX:
      beta=.295, p=.092), while controlling for age, gender, aspirin use,
      antidepressant use, and preexisting CVD. Bivariate correlations showed delayed NE
      recovery was also associated with increased PSEL reactivity (r=.416) and delayed
      PSEL recovery (r=.372; all ps<.05) among CG but not NC. DISCUSSION: Among
      chronically stressed caregivers, increased levels of depressive and anxious
      symptoms are associated with prolonged sympathetic activation and pronounced
      platelet activation. These changes may represent one pathway linking caregiving
      stress to cardiovascular risk.

PMID- 18054199
TI  - Spontaneous recovery from early glomerular inflammation is associated with
      resistance to anti-GBM glomerulonephritis: tolerance and autoimmune tissue
      injury.
AB  - Different susceptibility to anti-GBM glomerulonephritis (GN) among animal strains
      has been reported. Using our rat model for T cell-mediated anti-GBM GN, this
      study initiated an investigation on the mechanism related with GN susceptibility.
      Anti-GBM GN was induced either through immunization with the nephritogenic T cell
      epitope pCol(28-40) from Col4alpha3NC1 or through the transfer of specific T
      cells. WKY rats were highly susceptible to GN while immuno-compatible LEW rats
      were GN-resistant. GN-resistance in LEW rats was not associated to the immune
      response to pCol(28-40). First, both strains mounted a Th1 T cell response to
      pCol(28-40) with identical specificities; transfer of T cells from LEW to WKY
      rats induced glomerular injury. Second, co-transfer of antibody from WKY to LEW
      failed to induce GN. Time-course studies revealed that LEW rats did develop T
      cell-mediated inflammation in glomeruli at early stages similar to WKY rats, as
      evidenced by histopathology, proteinuria, CD4(+) T cell infiltration in
      glomeruli, and glomerular expression of inflammatory molecules. However,
      glomerular inflammation in LEW rats was transient followed by a full recovery.
      Thus, GN-resistance in LEW rats was due to its ability to contain early T cell
      mediated autoimmune glomerular damage. Our model may reveal a potential tolerance
      mechanism after autoimmune tissue damage has been initiated.

PMID- 18054200
TI  - xCT expression reduces the early cell cycle requirement for calcium signaling.
AB  - Calcium has long been recognized as an important regulator of cell cycle
      transitions although the mechanisms are largely unknown. A functional genomic
      screen has identified genes involved in the regulation of early cell cycle
      progression by calcium. These genes when overexpressed confer the ability to
      bypass the G1/S arrest induced by Ca(2+)-channel antagonists in mouse
      fibroblasts. Overexpression of the cystine-glutamate exchanger, xCT, had the
      greatest ability to evade calcium antagonist-induced cell cycle arrest. xCT
      carries out the rate limiting step of glutathione synthesis in many cell types
      and is responsible for the uptake of cystine in most human cancer cell lines.
      Functional analysis indicates that the cystine uptake activity of xCT overcomes
      the G1/S arrest induced by Ca(2+)-channel antagonists by bypassing the
      requirement for calcium signaling. Since cells overexpressing xCT were found to
      have increased levels and activity of the AP-1 transcription factor in G1, redox
      stimulation of AP-1 activity accounts for the observed growth of these cells in
      the presence of calcium channel antagonists. These results suggest that reduced
      calcium signaling impairs AP-1 activation and that xCT expression may directly
      affect cell proliferation.

PMID- 18054201
TI  - Increased levels of serotonin 2A receptors and serotonin transporter in the CNS
      of neuregulin 1 hypomorphic/mutant mice.
AB  - Changes in neuregulin 1 expression have been reported in the CNS from subjects
      with schizophrenia. As neuregulin 1 is important in cortical development we
      postulated that changes in neuregulin 1 expression may contribute towards changes
      in cholinergic, glutamatergic and serotonergic markers that are well documented
      in the CNS of subjects with that disorder. To begin to test this hypothesis, we
      used in situ radioligand binding to measure levels of muscarinic M1/M4 receptors,
      the kainate receptor, the NMDA receptor, the serotonin 2A receptor, the serotonin
      1A receptor and the serotonin transporter in the CNS from heterozygous
      transmembrane domain neuregulin 1 mutant mice. The major outcomes from these
      studies was the demonstration of an overall increase in levels of the serotonin
      2A receptor (F=11.3, d.f.=3,1,72, p=0.0012) and serotonin transporter (F=5.00,
      d.f.=1,3,72, p<0.05) in the mutant mice. Levels of the other receptors did not
      vary in the mutant mice compared to their wild type-like litter mates. These data
      are the first evidence to suggest that NRG1 gene expression may be involved in
      regulating the development of the serotonergic system in the mammalian CNS.

PMID- 18054202
TI  - Rapid evolving RNA gene HAR1A and schizophrenia.

PMID- 18054203
TI  - Single nucleotide polymorphisms of VEGF gene and Psoriasis risk.

PMID- 18054204
TI  - Impact of non-ionic surfactant on the long-term development of lab-scale
      activated sludge bacterial communities.
AB  - The development of bacterial communities in replicate lab-scale-activated sludge
      reactors degrading a non-ionic surfactant was evaluated by statistical analysis
      of denaturing gradient gel electrophoresis (DGGE) fingerprints. Four sequential
      batch reactors were fed with synthetic sewage, two of which received, in
      addition, 0.01% of nonylphenol ethoxylates (NPE). The dynamic character of
      bacterial community structure was confirmed by the differences in species
      composition among replicate reactors. Measurement of similarities between
      reactors was obtained by pairwise similarity analysis using the Bray Curtis
      coefficient. The group of NPE-amended reactors exhibited the highest similarity
      values (Sjk=0.53+/-0.03), indicating that the bacterial community structure of
      NPE-amended reactors was better replicated than control reactors (Sjk=0.36+/
      0.04). Replicate NPE-amended reactors taken at different times of operation
      clustered together, whereas analogous relations within the control reactor
      cluster were not observed. The DGGE pattern of isolates grown in conditioned
      media prepared with media taken at the end of the aeration cycle grouped
      separately from other conditioned and synthetic media regardless of the carbon
      source amendment, suggesting that NPE degradation residuals could have a role in
      the shaping of the community structure.

PMID- 18054205
TI  - Extracellular fatty acids facilitate flagella-independent translocation by
      Stenotrophomonas maltophilia.
AB  - Stenotrophomonas maltophilia is widespread in natural environments such as soil,
      sewage and plant rhizospheres. Surfactants frequently function in modulating
      bacterial surface translocation. In this study, rpfB and rpfF orthologues were
      identified from S. maltophilia strain WR-C, which was isolated from the clogged
      zone of a septic system. These genes play a role in the biosynthesis of eight
      extracellular compounds that facilitated flagella-independent translocation by
      the wild-type or a flagella-defective mutant. This type of surface translocation
      has not been reported previously for this organism. These eight compounds include
      cis-delta 2-11-methyl-dodecenoic acid and seven structural derivatives. Two are
      saturated fatty acids; the others are unsaturated fatty acids with double bonds
      at position 2. These fatty acids vary in chain length from 12 to 14 carbons and
      in the position of the branched methyl group. Our results demonstrated that
      independently cis-delta 2-11-methyl-dodecenoic acid and 11-methyl-dodecanoic acid
      promoted flagella-independent translocation by S. maltophilia strain WR-C by
      acting as wetting agents.

PMID- 18054206
TI  - Identification of novel plasmid-mediated extended-spectrum beta-lactamase CTX-M
      57 in Salmonella enterica serovar Typhimurium.

PMID- 18054207
TI  - In vitro efficacy of voriconazole against clinical isolates of Scytalidium spp.
      from clinical lesions.

PMID- 18054208
TI  - Platelet 18 kDa Translocator Protein density is reduced in depressed patients
      with adult separation anxiety.
AB  - RATIONALE: Recent studies indicate that Adult Separation Anxiety Disorder (ASAD)
      may represent a discrete diagnostic entity worthy of attention. Adults with
      separation anxiety report extreme anxiety and fear about separations from major
      attachment figures (partner, children or parents). These symptoms affect
      individual's behavior, lead to severe impairment in social relationships and are
      not better accounted for by the presence of agoraphobia. In a previous study we
      found platelet expression reduction of the 18 kDa Translocator Protein (TSPO)
      (the new nomenclature for the peripheral-type benzodiazepine receptor) in
      patients with panic disorder who also fulfilled the diagnostic criteria for ASAD.
      OBJECTIVES: To explore whether separation anxiety might be a factor
      differentiating TSPO expression in a sample of patients with major depression.
      METHODS: The equilibrium binding parameters of the specific TSPO ligand [3H]PK
      11195 were estimated on platelet membranes from 40 adult outpatients with DSM-IV
      diagnosis of MDD, with or without separation anxiety symptoms, and 20 healthy
      controls. Patients were assessed by SCID-I, HAM-D, the Structured Clinical
      Interview for Separation Anxiety Symptoms (SCI-SAS-A) and the Adult Separation
      Anxiety Self-report Checklist (ASA-27). RESULTS: A significant reduction of
      platelet TSPO density mean value was found in depressed patients with associated
      ASAD symptoms, while no significant differences were found between depressed
      patients without ASAD and the control group. Individual TSPO density values were
      significantly and negatively correlated with both SCI-SAS-A and ASA-27 total
      scores, but not with HAM-D total score or HAM-D anxiety/somatization factor
      score. CONCLUSIONS: The reduction of platelet TSPO density in our sample of
      patients with depression was specifically related to the presence of ASAD. These
      data suggest that TSPO expression evaluation is a useful biological marker of
      ASAD.

PMID- 18054209
TI  - Paroxetine with pindolol augmentation: a double-blind, randomized, placebo
      controlled study in depressed in-patients.
AB  - Pindolol, a 5-HT1A autoreceptor antagonist, given in combination with selective
      serotonin reuptake inhibitors (SSRIs), may enhance and/or accelerate the
      therapeutic efficacy of SSRIs. Fifty patients, meeting ICD-10 criteria for major
      depressive disorder or bipolar depression, were enrolled in our randomized,
      placebo-controlled, double-blind trial. One group received paroxetine plus
      pindolol (2.5 mg t.i.d.), and the other group received paroxetine plus placebo.
      The proportion of patients with sustained response (>or=50% reduction of baseline
      HAM-D 17 score maintained until the endpoint; p=0.252) and the proportion of
      patients with remission (HAM-D 17 <or=8 at last visit; p=0.769) did not differ
      significantly between the two treatment groups. However, a significantly greater
      proportion of patients who were not previously treated with antidepressants
      (n=15; p=0.041) and of patients with bipolar depression (n=11; p=0.015) had a
      sustained response in the paroxetine plus pindolol group compared to the
      paroxetine plus placebo group; furthermore there was a trend for first episode
      depressed patients to have a greater response in the paroxetine plus pindolol
      group (n=12; p=0.071). Summarizing, the entire study population showed no
      antidepressive benefit from pindolol augmentation. Nevertheless patients with
      bipolar depression irrespective of previous treatments and duration of illness,
      and unipolar patients not previously treated demonstrated a significant benefit
      from pindolol augmentation.

PMID- 18054210
TI  - The spikes trains probability distributions: a stochastic calculus approach.
AB  - We discuss the statistics of spikes trains for different types of integrate-and
      fire neurons and different types of synaptic noise models. In contrast with the
      usual approaches in neuroscience, mainly based on statistical physics methods
      such as the Fokker-Planck equation or the mean-field theory, we chose the point
      of the view of the stochastic calculus theory to characterize neurons in noisy
      environments. We present four stochastic calculus techniques that can be used to
      find the probability distributions attached to the spikes trains. We illustrate
      the power of these techniques for four types of widely used neuron models.
      Despite the fact that these techniques are mathematically intricate we believe
      that they can be useful for answering questions in neuroscience that naturally
      arise from the variability of neuronal activity. For each technique we indicate
      its range of applicability and its limitations.

PMID- 18054211
TI  - What do electrophysiological studies tell us about processing at the olfactory
      bulb level?
AB  - Electrophysiological recordings performed in the mammalian olfactory bulb (OB)
      aimed at deciphering neural rules supporting neural representation of odors. In
      spite of a fairly large number of available data, no clear picture emerges yet in
      the mammalian OB. This paper summarizes some important findings and underlines
      the fact that difference in experimental conditions still represents a major
      limitation to the emergence of a synthetic view. More specifically, we examine to
      what extent the absence or the presence of anaesthetic influence OB neuronal
      responsiveness. In addition, we will see that recordings of either single cell
      activity or populational activity provide quite different pictures. As a result
      some experimental approaches provide data underlying sensory properties of OB
      neurons while others emphasize their capabilities of integrating incoming sensory
      information with attention, motivation and previous experience.

PMID- 18054212
TI  - Influence of maternal nicotine exposure during gestation and lactation on lactate
      dehydrogenase isoenzyme profile and transcript levels in developing neonatal rat
      lung.
AB  - In this study we investigated the effect of (a) aging on rat lung lactate
      dehydrogenase (LDH) mRNA expression and isoenzyme profile and, (b) the effect of
      maternal nicotine exposure during gestation and lactation on LDH isoenzyme
      profile and mRNA expression in the lungs of the offspring. Pregnant rats were
      injected subcutaneously (1mg nicotine/kg body weight/day) from day 1 after
      mating. Lung tissue to determine LDH isoenzyme profile and mRNA expression was
      obtained from the offspring. LDH mRNA expression and isoenzyme profile was
      determined on postnatal days 1, 7, 14, 21 and 49. Generally the %Densities of all
      the isoenzymes decreased between postnatal days 1 and 49. Between postnatal days
      7 and 14, a period associated with rapid alveolar formation, all isoenzymes
      except LDH-1, decreased (P<0.01). During this period all the isoforms in nicotine
      exposed lung increased (P<0.05). In both control and nicotine-exposed lung LDH-1
      is the dominant isoenzyme. The LDH-M and LDH-H isoenzyme levels are higher
      (P<0.001) in the lungs of the nicotine exposed rats. Maternal nicotine exposure
      during gestation and lactation changed the metabolic status of the nicotine
      exposed lungs to become more glycolytic compared to that of the control lung.
      These changes in LDH isoenzyme profiles and mRNA expression are irreversible.

PMID- 18054213
TI  - Reactive and proliferative changes of splenic reticulum cells of rats
      investigated with special staining methods and immunohistochemistry.
AB  - In the rat spleen, reactive and proliferative changes of the reticulum cells are
      rare events and seem to occur almost exclusively in the red pulp. The normal
      structure of the splenic reticulum cell and fiber lattice and examples of
      spontaneous and induced pathological alterations were investigated by
      immunohistochemistry (smooth muscle-actin, vimentin, S100 and proliferating cell
      nuclear antigen) and special stains for extracellular fibers (silver
      impregnation, azan). In response to congestion, systemic tumor growth or
      treatment with a hematotoxic compound, the scaffold cells increased either their
      contractile properties or their production of extracellular fibers. Primary focal
      hyperplasias of stromal cells which had developed without obvious cause were
      characterized by vanishing of sinuses, increased fiber content, increased
      expression of sm-actin or foci of lipomatosis. The borders of focal hyperplasias
      were indistinct and they did not infiltrate the white pulp compartments.
      Neoplasms of the stromal reticulum cells resembled soft tissue tumors in other
      organs. Specific tumor entities as described in other species have so far not
      been observed in the rat.

PMID- 18054214
TI  - ESTP comments on the draft updated OECD test guideline 407.
AB  - The revision of the OECD TG 407 test guideline (repeated dose 28-day oral
      toxicity study in rodents) focuses on endpoints to detect endocrine activities of
      chemicals. The new endpoints are likely to influence other previously established
      core endpoints of this study type. An expert group of pathologists and
      toxicologists within the European Society of Toxicologic Pathologists (ESTP) has
      contributed to the scientific discussion of the draft guideline. The advantages
      and disadvantages of methodical changes as necropsy of all females in dioestrus,
      blood collection for clinical chemistry and haematology at the same cycle stage,
      weighing of the thyroid gland and separate weighing of ventral and dorsolateral
      lobes of the prostate are considered. Possible alternatives are pointed out
      covering scientific as well as practical aspects.

PMID- 18054215
TI  - The larval head of Raphidia (Raphidioptera, Insecta) and its phylogenetic
      significance.
AB  - External and internal head structures of larval representatives of Raphidiidae
      are described. The obtained data were compared to characters of other neuropterid
      larvae and to larval characters of representatives of other endopterygote
      lineages. Characters potentially relevant for phylogenetic reconstruction are
      listed and discussed. The larvae of Raphidioptera differ distinctly from other
      neuropterid larvae in their morphology. They are mainly characterised by
      autapomorphic and plesiomorphic character states and few features indicate
      systematic affinities with other groups. Endopterygote groundplan features
      maintained in Raphidioptera are the complete tentorium, the free labrum, the full
      set of labral muscles, the presence of four extrinsic antennal muscles, the three
      segmented labial palpi, the presence of a full set of extrinsic maxillary and
      labial muscles, the presence of a salivarium, and possibly the high number of
      stemmata. Apomorphies likely correlated with predaceous habits are the long gula,
      the protracted maxillae, the longitudinal arrangement of extrinsic maxillary
      muscles, and the elongated prepharyngeal tube. Highly unusual, potentially
      autapomorphic features are the presence of a dorsal ligament of the tentorium and
      paired gland-like structures below the pharynx. A prognathous or very slightly
      inclined head and slender mandibles without mola are features shared by larvae of
      all orders of Neuropterida. The parallel-sided head is a potential synapomorphy
      of Raphidioptera and Megaloptera. A fully prognathous head with anteriorly
      shifted posterior tentorial grooves and the presence of a parietal ridge and a
      distinct neck region are features shared with Corydalidae. Characters of the
      larval head are not sufficient for a reliable placement of Raphidioptera.

PMID- 18054216
TI  - Comparative analysis of the size and shape of the lizard eye.
AB  - Lizards occupy both scotopic (light-limited) and photopic (light-rich)
      environments, thereby making this clade ideal for analyses of eye morphology
      adaptations. This study examines how in lizards the morphology of the eye varies
      according to activity in these different light environments. Measurements were
      collected on corneal diameters and axial lengths of the eye for 239 specimens of
      116 lizard species (including Sphenodon) that include both species with scotopic
      and photopic visual adaptations. I show that the light level available to a
      lizard for vision has a significant effect on eye shape and size. Scotopic
      lizards have eye shapes that are optimized for visual sensitivity, with larger
      corneal diameters relative to axial lengths. However, photopic lizards do not
      exhibit absolutely larger axial lengths than do scotopic lizards, and the groups
      have the same absolute axial lengths of the eye. Results also indicate that the
      light level the lizard functions under is a more significant influence on eye
      shape, as defined by the relationship between corneal diameter and axial length
      of the eye, than is phylogeny.

PMID- 18054217
TI  - Folic acid and polyunsaturated fatty acids improve cognitive function and prevent
      depression, dementia, and Alzheimer's disease--but how and why?
AB  - Low blood folate and raised homocysteine concentrations are associated with poor
      cognitive function. Folic acid supplementation improves cognitive function. Folic
      acid enhances the plasma concentrations of docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA). EPA, DHA, and arachidonic acid (AA) are of benefit
      in dementia and Alzheimer's disease by up-regulating gene expression concerned
      with neurogenesis, neurotransmission and connectivity, improving endothelial
      nitric oxide (eNO) generation, enhancing brain acetylcholine levels, and
      suppressing the production of pro-inflammatory cytokines. EPA, DHA, and AA also
      form precursors to anti-inflammatory compounds such as lipoxins, resolvins, and
      neuroprotectin D1 (NPD1) that protect neurons from the cytotoxic action of
      various noxious stimuli. Furthermore, various neurotrophins and statins enhance
      the formation of NPD1 and thus, protect neurons from oxidative stress and prevent
      neuronal apoptosis Folic acid improves eNO generation, enhances plasma levels of
      EPA/DHA and thus, could augment the formation of NPD1. These results suggest that
      a combination of EPA, DHA, AA and folic acid could be of significant benefit in
      dementia, depression, and Alzheimer's disease and improve cognitive function.

PMID- 18054218
TI  - Role of adipocytokines in obesity-associated insulin resistance.
AB  - The rapid increase of obese population in the United States has made obesity into
      epidemic proportion. Obesity is a strong risk factor for metabolic syndrome, type
      2 diabetes mellitus, cardiovascular diseases, cancer and other diseases.
      Compelling evidence has demonstrated that increased adipose tissue mass is not
      only the consequence of obesity, but also plays a central role in the development
      of obesity-associated diseases. Recent studies have profoundly changed the
      concept of adipose tissue from being an energy depot to an active endocrine
      organ. The development of obesity alters adipocyte-derived hormones or cytokines
      expression, which provide a link between obesity and impaired insulin sensitivity
      and metabolic defects in other tissues. This review summarizes the current
      knowledge on how major adipose-derived hormones or adipocytokines influence
      insulin sensitivity.

PMID- 18054219
TI  - Rapidly inducible, genetically targeted inactivation of neural and synaptic
      activity in vivo.
AB  - Inducible and reversible perturbation of the activity of selected neurons in vivo
      is critical to understanding the dynamics of brain circuits. Several genetically
      encoded systems for rapid inducible neuronal silencing have been developed in the
      past few years offering an arsenal of tools for in vivo experiments. Some systems
      are based on ion-channels or pumps, others on G protein coupled receptors, and
      yet others on modified presynaptic proteins. Inducers range from light to small
      molecules to peptides. This diversity results in differences in the various
      parameters that may determine the applicability of each tool to a particular
      biological question. Although further development would be beneficial, the
      current silencing tool kit already provides the ability to make specific
      perturbations of circuit function in behaving animals.

PMID- 18054220
TI  - The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue
      would account for the improvement of herpetic stromal keratitis in mice.
AB  - Herpes simplex virus type 1 (HSV-1) induces an ocular chronic immunoinflammatory
      syndrome named herpetic stromal keratitis that can lead to vision impairment and
      blindness. We have reported that the synthetic brassinosteroid (22S,23S)-3beta
      bromo-5alpha,22,23-trihydroxystigmastan-6-one, designated as 2, is a potent
      antiviral in vitro and reduces the incidence of murine herpetic stromal
      keratitis, although it does not exert an antiviral effect in vivo. In the present
      report, we investigated whether brassinosteroid 2 may play a role in the
      modulation of the response of epithelial and immune cells to HSV-1 infection.
      Compound 2 blocked HSV-1-induced activation of NF-kappaB by inhibiting its
      translocation to the nucleus of infected corneal and conjunctival cells in vitro,
      as well as significantly reduced the secretion of TNF-alpha in infected NHC
      cells. Conversely, IL-6 production was enhanced by compound 2 after HSV-1
      infection in both cell types. The production of these cytokines was considerably
      reduced in a LPS-stimulated macrophage cell line after treatment with compound 2.
      In conclusion, brassinosteroid 2 would be playing a modulating effect as an
      inductor or inhibitor, depending on the cell type involved. The improvement of
      disease observed in mice could be a balance between both, the immunostimulating
      and immunosuppressive effects of brassinosteroid 2 in vivo.

PMID- 18054221
TI  - Total mesorectal excision (TME) with laparoscopic approach: 226 consecutive
      cases.
AB  - BACKGROUND: Total mesorectal excision (TME) of the rectum has been advocated as
      the gold surgical treatment of the middle and low third rectal cancer.
      Laparoscopy has gained acceptance among surgeons in the treatment of colon
      malignancies, while scepticism exists about laparoscopic TME in term of safety,
      and its oncological adequacy. OBJECTIVE: To evaluate the impact of laparoscopic
      TME on surgical and oncological outcome in a group of consecutive unselected
      patients. METHODS: 226 unselected patients with rectal cancer underwent
      laparoscopic TME from January 1998 to August 2007. Patients staged cT3/4 cTxN+
      were submitted to neoadjuvant treatment. Postoperative complications and
      oncological outcome were registered. RESULTS: Mean distance of the tumour from
      the anal verge was 6.2+/-2 cm. 48.6% of patients were enrolled in "long-course"
      neoadjuvant chemo-radiotherapy (partial and complete response rates 72.4% and
      20.1%, respectively). Surgical procedures were 202 anterior and 24 abdominal
      perineal resections. Mean operative time 245.3+/-58.4 min, mean blood loss 203+/
      176 mL. Conversion rate 6.1%. Thirty-days morbidity rate 31.8% without mortality.
      Anastomotic leaks rate was 16.8%. Reoperation rate 6.6%. Gastrointestinal
      recovery rate was 3.1+/-1.4 days and hospital stay 10.4+/-4.6 days. Concerning
      adequacy of oncologic resection, mean distance between tumour and margin of
      resection was 2.7+/-2 cm with a nodal sampling of 14.4+/-4.6. Six patients (2.6%)
      had a R1 margin. With a mean follow-up of 39.8 months non port-site metastases
      occurred. Local recurrence rate was 6.1%. Five years cumulative overall survival
      was 81% and disease-free survival was 70% (Kaplan-Meier method). CONCLUSIONS:
      Laparoscopic approach for rectal tumour is a technically demanding procedure, but
      it is safe and it has the feature of an oncologic procedure.

PMID- 18054222
TI  - In situ bioremediation of monoaromatic pollutants in groundwater: a review.
AB  - Monoaromatic pollutants such as benzene, toluene, ethylbenzene and mixture of
      xylenes are now considered as widespread contaminants of groundwater. In situ
      bioremediation under natural attenuation or enhanced remediation has been
      successfully used for removal of organic pollutants, including monoaromatic
      compounds, from groundwater. Results published indicate that in some sites,
      intrinsic bioremediation can reduce the monoaromatic compounds content of
      contaminated water to reach standard levels of potable water. However,
      engineering bioremediation is faster and more efficient. Also, studies have shown
      that enhanced anaerobic bioremediation can be applied for many BTEX contaminated
      groundwaters, as it is simple, applicable and economical. This paper reviews
      microbiology and metabolism of monoaromatic biodegradation and in situ
      bioremediation for BTEX removal from groundwater under aerobic and anaerobic
      conditions. It also discusses the factors affecting and limiting bioremediation
      processes and interactions between monoaromatic pollutants and other compounds
      during the remediation processes.

PMID- 18054223
TI  - Pathways for development of a biorenewables industry.
AB  - The advanced energy initiative to reduce the nation's future demand for oil has
      resulted in the definition of a number of pathways for the development of the bio
      renewables industry. This paper gives an overview of the pathways which could
      lead to both ethanol and other types of bio-products. The methods that would be
      used for cellulose conversion also apply to adding value for the co-products of
      ethanol production. Process milestones and pathways for research that would
      enable corn dry mill operations to improve are described. A corn dry mill
      improvement pathway is outlined, and introduces the topics that are covered in
      this particular special volume.

PMID- 18054224
TI  - Production of streptomycin from chitin using Streptomyces griseus in bioreactors
      of different configuration.
AB  - Streptomyces griseus was cultured in three different bioreactors in a medium
      containing chitin flakes. When a conventional bioreactor stirred by two sets of
      Rushton impellers and operated at high speed was used, the yield of streptomycin
      (3.1mg/l) was the highest observed and occurred at approximately 500 h.
      Cultivation of S. griseus in a bioreactor stirred at low speed by a U-shaped
      paddle resulted in a lower yield of streptomycin (1.8 mg/l) but this was achieved
      in a shorter period of time (400 h). Increasing the concentration of chitin from
      5% to 10% w/v had no significant effect on either of these two parameters. The
      use of a novel vertical basket bioreactor in which the chitin flakes were
      contained within a wire mesh basket and were gently fluidised by air, enabled
      comparatively high yields of streptomycin (2.8 mg/l) in the relatively short time
      of 300 h.

PMID- 18054225
TI  - Inhibiting dihydrodipicolinate synthase across species: towards specificity for
      pathogens?
AB  - Dihydrodipicolinate synthase (DHDPS) is a key enzyme in lysine biosynthesis and
      an important antibiotic target. The specificity of a range of heterocyclic
      product analogues against DHDPS from three pathogenic species, Bacillus
      anthracis, Mycobacterium tuberculosis and methicillin-resistant Staphylococcus
      aureus, and the evolutionarily related N-acetylneuraminate lyase, has been
      determined. The results suggest that the development of species-specific
      inhibitors of DHDPS as potential antibacterials is achievable.

PMID- 18054226
TI  - Microwave-assisted synthesis of dihydropyrimidin-2(1H)-ones using graphite
      supported lanthanum chloride as a mild and efficient catalyst.
AB  - Graphite supported lanthanum chloride efficiently catalyzes the three-component
      coupling of beta-ketoesters, aldehydes and urea/thiourea to afford corresponding
      dihydropyrimidinones in good yields under microwave irradiation.

PMID- 18054227
TI  - Structure-activity relationship and pharmacokinetic profile of 5-ketopyrazole
      factor Xa inhibitors.
AB  - Efforts to further optimize the clinical candidate razaxaban have led to a new
      series of pyrazole-based factor Xa (fXa) inhibitors. Designed to prevent the
      potential formation of primary aniline metabolites in vivo, the nitrogen of the
      carboxamido linker between the pyrazole and proximal phenyl moiety of the
      razaxaban scaffold was replaced with a methylene group. The resulting ketones
      demonstrated excellent potency and selectivity for fXa but initially had poor
      oral bioavailability. Optimization by conversion from a P1 aminobenzisoxazole to
      a P1 p-methoxyphenyl residue, replacing the 3-trifluoromethylpyrazole with a 3
      amidopyrazole, and employing a pyridone P4 group provided a fXa inhibitor with a
      potency and pharmacokinetic profile equivalent to that of razaxaban and improved
      selectivity over thrombin.

PMID- 18054228
TI  - Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones
      with biaryl P4 motifs.
AB  - Structure and property based drug design was exploited in the synthesis of
      sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating
      biaryl P4 groups, producing highly potent inhibitors with encouraging oral
      pharmacokinetic profiles and significant but sub-optimal anticoagulant
      activities.

PMID- 18054229
TI  - Development of potent, allosteric dual Akt1 and Akt2 inhibitors with improved
      physical properties and cell activity.
AB  - This letter describes the development of potent, allosteric dual Akt1 and Akt2
      inhibitors with improved aqueous solubility (approximately 18 mg/mL) that
      translates into enhanced cell activity and caspase-3 induction.

PMID- 18054230
TI  - (2S,2'R)-analogue of LG190178 is a major active isomer.
AB  - Vitamin D receptor (VDR) ligands are therapeutic agents for the treatment of
      psoriasis, osteoporosis, and secondary hyperparathyroidism. VDR ligands also show
      immense potential as therapeutic agents for autoimmune diseases and cancers of
      the skin, prostate, colon, and breast as well as leukemia. LG190178 is a novel
      non-secosteroidal ligand for VDR. We synthesized and evaluated stereoisomers of
      LG190178 and found that only an (2S,2'R)-analogue of LG190178 (YR301) had strong
      activity.

PMID- 18054231
TI  - Improving B mode ultrasound evaluation of breast lesions with real-time
      ultrasound elastography--a clinical approach.
AB  - Ultrasound elastography using the extended combined auto-correlation method of
      tissue elasticity allows for real-time strain image visualisation using a free
      hand probe with concurrent conventional B mode imaging. Four hundred and fifteen
      consecutive women with 550 breast lesions confirmed on B mode ultrasound were
      assessed with elastography using the elasticity score. There were 119 malignant
      and 431 benign lesions. The elastography sensitivity was 78.0%, specificity was
      98.5% and overall accuracy was 93.8%. The median score for malignancy was 5 and
      that for benign lesions was 2. There was good correlation with B mode BIRADS
      category. 98.6% of lesions with an elasticity score of 2 or below (95%CI=96.8
      99.4) were benign. BIRADS 3 lesions with an elasticity score of 2 or below may be
      re-classified as BIRADS 2 lesions. We found that 15.3% of BIRADS 2 and 3 lesions
      with an elasticity score of 3 were malignant. Real-time ultrasound elastography
      is user-friendly with a high accuracy rate, thereby improving B mode ultrasound
      assessment.

PMID- 18054233
TI  - Quantity versus quality of gait and quality of life in patients with
      osteoarthritis.
AB  - PURPOSE: This study investigated the relationship between the quality of life,
      quality of gait and the quantity of gait in patients with impairments in the
      lower extremities. METHODS: Twenty-six subjects (age 58.6+/-13.4 years) suffering
      from knee or hip osteoarthritis were investigated before implantation of an
      endoprosthesis. Quality of life was assessed using the SF-36 survey. The quality
      of gait was assessed with a six camera motion analysis system in combination with
      two force plates. For evaluation of the quantity of gait, two monitors were
      applied: (a) the accelerometer-based DynaPort activity monitor measured
      locomotion and posture for 1 day and (b) The Step-Activity-Monitor, a small
      microprocessor-operated acceleration sensor, measured the number of gait cycles
      in 1-min intervals for 1 week. Spearman correlation coefficients were calculated
      between quantity of gait, quality of gait and quality of life. RESULTS: The
      patients showed typical gait impairments caused by osteoarthritis. Locomotion
      accounted for 10.5+/-5% of the daily recorded time, 4782+/-2116 gait cycles were
      counted per day. The sub-categories of the SF-36 showed limited physical
      functioning and general health with 38 and 56 out of 100 points, respectively.
      Computation of Spearman-rho revealed no relevant correlations between quality and
      quantity of gait but moderate correlations between quality of life and quantity
      of gait. CONCLUSION: The findings underline that a patient's level of mobility
      cannot be reliably estimated from quality of gait or from quality of life.
      Instead, adequate methods should be chosen to measure the quantity of gait in
      daily life.

PMID- 18054232
TI  - Is surgical excision necessary in benign papillary lesions initially diagnosed at
      core biopsy?
AB  - Debate continues regarding the use of surgical excision in benign papillary
      lesions initially diagnosed at core biopsy. The objective of this study is to
      propose management guidelines for benign papillary breast lesions initially
      diagnosed at core biopsy. Between January 2003 and January 2006, 76 lesions were
      identified as benign papillary lesions at initial core needle biopsy (n=68) or
      vacuum biopsy (n=8). After surgical excision, six of the 68 benign papillary
      lesions initially diagnosed at core needle biopsy were confirmed as malignant
      papillary neoplasms, giving a false-negative rate of core needle biopsy of 8.8%.
      Three of the eight atypical papillomas initially diagnosed at core needle biopsy
      were confirmed as papillary cancer in final pathology, giving a false-negative
      rate of 37.5%. In the analysis of the difference between benign papillary lesions
      and atypia or malignant papillary lesions, malignant papillary lesions were
      located more peripherally (p=0.005) than benign lesions and were larger (>1.5 cm,
      p=0.017). It is concluded that atypical papillomas at initial core biopsy or
      large, clinically peripherally located papillomas (>1.5 cm) need additional
      surgical excision.

PMID- 18054234
TI  - 14-3-3 cruciform-binding proteins as regulators of eukaryotic DNA replication.
AB  - Cruciforms are secondary DNA structures, serving as recognition signals at or
      near eukaryotic (yeast and mammalian) origins of DNA replication. The cruciform
      binding protein is a member of the 14-3-3 protein family and binds to origins of
      DNA replication in a cell cycle-dependent manner. Five 14-3-3 protein isoforms
      (beta, gamma, epsilon, zeta and sigma) have been identified as having cruciform
      binding activity.

PMID- 18054235
TI  - Fuzzy complexes: polymorphism and structural disorder in protein-protein
      interactions.
AB  - The notion that all protein functions are determined through macromolecular
      interactions is the driving force behind current efforts that aim to solve the
      structures of all cellular complexes. Recent findings, however, demonstrate a
      significant amount of structural disorder or polymorphism in protein complexes, a
      phenomenon that has been largely overlooked thus far. It is our view that such
      disorder can be classified into four mechanistic categories, covering a
      continuous spectrum of structural states from static to dynamic disorder and from
      segmental to full disorder. To emphasize its generality and importance, we
      suggest a generic term, 'fuzziness', for this phenomenon. Given the crucial role
      of protein disorder in protein-protein interactions and in regulatory processes,
      we envision that fuzziness will become integral to understanding the interactome.

PMID- 18054236
TI  - Electron crystallography of biomolecules: mysterious membranes and missing cones.
AB  - One of the major challenges facing structural biologists today is the
      determination of high-resolution 3D structures of membrane proteins. The
      requirement for detergent molecules to be present makes X-ray crystallography
      particularly difficult, coupled with the added problems of isolating sufficient
      (viable) protein samples at high enough concentrations to yield 3D crystals. One
      technique that enables structural determination with fewer constraints is
      electron crystallography of two-dimensional crystals, in which small amounts of
      membrane proteins can be studied in native form in lipid bilayers.

PMID- 18054237
TI  - 'Snapping' knee secondary to a tibial osteochondroma.
AB  - INTRODUCTION: Osteochondroma is the most common bone tumour and is usually found
      around the knee. Typical presentations range form painless masses around the
      joint to mechanical irritation caused by direct pressure over surrounding
      muscles. Snapping of the knee caused by an osteochondroma however has not been
      described in literature. METHOD: An active 19-year-old gentleman presented with
      snapping of the left medial hamstring tendon for over 5 years, but with recent
      increase in frequencies of attack. The patient was initially diagnosed to have a
      sporting injury. Radiological investigation showed an opaque lesion on the medial
      border of the proximal tibia, which was suggestive of an osteophyte. RESULTS: The
      lump was surgically excised and the patient made good recovery with resolution of
      symptoms. Histological results revealed the lesion to be that of an
      osteochondroma. CONCLUSION: Although rare, osteochondroma should be considered as
      a differential when approaching a case of snapping knee pain.

PMID- 18054238
TI  - Orally active 1,2,4-trioxepanes: synthesis and antimalarial activity of a series
      of 7-arylvinyl-1,2,4-trioxepanes against multidrug-resistant Plasmodium yoelii in
      Swiss mice.
AB  - 7-Arylvinyl-1,2,4-trioxepanes 7a-d, 8a-d, 9a-d, 10a-d, 11a-c, and 12a-c, prepared
      by photooxygenation of homoallylic alcohols 5a-d, were evaluated against multi
      drug resistant Plasmodium yoelii nigeriensis in Swiss mice by oral and
      intramuscular routes. Trioxepane 11c, the most active compound of the series,
      showed more than 98% suppression of parsitaemia at 96 mg/kg by both oral and
      intramuscular routes. This is the first report on in vivo active 1,2,4
      trioxepanes.

PMID- 18054239
TI  - Phenylalanine-containing hydroxamic acids as selective inhibitors of class IIb
      histone deacetylases (HDACs).
AB  - We synthesized biarylalanine-containing hydroxamic acids and tested them on
      immunoprecipitated HDAC1 and HDAC6 and show a subtype selectivity for HDAC6 that
      was confirmed in cells by Western blot (tubulin vs histones). We obtained an X
      ray structure with a HDAC6-selective inhibitor with the bacterial deacetylase
      HDAH. Docking studies were carried out using HDAC1 and HDAC6 protein models.
      Antiproliferative activity was shown on cancer cells for selected compounds.

PMID- 18054240
TI  - Decisive factors for realizing atomic-column resolution using STEM and EELS.
AB  - We demonstrate atomic-column imaging by scanning transmission electron microscopy
      (STEM) and electron energy-loss spectroscopy (EELS). The silicon atomic-columns
      of a beta-Si3N4 (001) specimen are clearly resolved. The atomic-site dependence
      and the energy-loss dependence of the spatial resolution are elucidated on the
      basis of the experimental results and multislice calculations. We describe two
      decisive factors for realizing atomic-column imaging in terms of localization in
      elastic and inelastic scattering. One is the channeling of the incident probe due
      to dynamical diffraction, which has atomic-site dependence. The other is the
      localization in inelastic scattering; in addition to the energy-loss dependence
      of delocalization, we point out its dependence on the offset energy from the
      ionization energy, i.e., an additional localization factor concerning the Bethe
      surface. The present atomic-column observation of the Si-L core-loss image
      indicates that the local approximation, which can be interpreted intuitively, is
      achievable under appropriate experimental conditions, such as high-energy-loss, a
      small convergence angle and a large collection angle (e.g., 400 eV, 15 and 30
      mrad, respectively).

PMID- 18054241
TI  - Nanomaterial electronic structure investigation by valence electron energy loss
      spectroscopy - an example of doped ZnO nanowires.
AB  - The effects of doping (by ion implantation) on the electronic structure of ZnO
      nanowires, particularly on the defect states generation in the band gap of ZnO,
      are investigated using valence electron energy loss spectroscopy (VEELS)
      performed in a transmission electron microscope (TEM). The improved spectrum
      energy resolution via the introduction of a gun monochromator, together with the
      reduced intensity in the zero loss peak tail as realized by spectrum acquisition
      at non-zero momentum transfer, enable us to extract such electronic structure
      information from the very low loss region of the EEL spectra. We have compared
      the doping effects of several dopant elements, i.e., Er, Yb, and Co, and found
      that generation of the band tail states ( approximately 2-3.3eV) is a common
      consequence of the ion implantation process. On the other hand, specific mid-gap
      state(s) in the lower energy range are created only in the rare earth element
      doped ZnO nanowires, suggesting the dopant-sensitive nature of such state.

PMID- 18054242
TI  - Restricted expression of mutant SOD1 in spinal motor neurons and interneurons
      induces motor neuron pathology.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by the selective loss of motor neurons (MNs). Approximately 10% of ALS cases are
      familial (known as FALS), and approximately 20% of FALS cases are caused by
      mutations in Cu/Zn superoxide dismutase type 1 (SOD1). Mutant (MT) SOD1 induces
      FALS as a result of a toxicity that remains poorly defined. Several studies
      suggest that the toxicity involves a non-cell autonomous mechanism. In this
      study, we generated transgenic mice that had a restricted and repressible
      expression of MTSOD1 in spinal MNs and interneurons. Although the transgenic mice
      were not weak, they weighed less than control mice and had pathological and
      immunohistochemical abnormalities of MNs confined to cells that expressed MTSOD1.
      These results suggest that MTSOD1-induced MN degeneration is at least partly cell
      autonomous. Mouse models similar to the one presented here will be valuable for
      spatially and temporally controlling expression of mutant genes involved in
      neurodegenerative diseases.

PMID- 18054243
TI  - Salt stress increases the expression of p5cs gene and induces proline
      accumulation in cactus pear.
AB  - Proline (Pro) is one of the most accumulated osmolytes in salinity and water
      deficit conditions in plants. In the present study, we measured the Pro content,
      the activity and the expression level of delta 1-pyrroline-5-carboxylate
      synthetase (P5CS: gamma-glutamyl kinase, EC 2.7.2.11 and glutamate-5-semialdehyde
      dehydrogenase, EC 1.2.1.41), a key regulatory enzyme involved in the biosynthesis
      of Pro, in cactus pear (Opuntia streptacantha) subjected to 6, 9 and 11 days of
      salt stress. Treatment with NaCl of O. streptacantha young plants resulted in a
      decrease in the cladode thickness and root length, and in a significant and
      gradual accumulation of Pro in young cladodes, in a time- and concentration
      dependent manner. P5CS activity, studied as gamma-glutamyl kinase, was reduced at
      all times as a consequence of salt treatment, except at the sixth day at 75 and
      150mM of NaCl, where a slight increase was observed. We isolated an open reading
      frame (ORF) fragment of p5cs gene. The deduced amino acid sequence of the P5CS
      protein exhibited 90.4% of identity with the P5CS protein from Mesembryanthemum
      crystallinum. RT-PCR analysis revealed that the Osp5cs gene of O. streptacantha
      was induced by salt stress at 9 and 11 days of treatment. Furthermore, ABA
      induced Osp5cs gene expression was observed in cladodes of cactus pear young
      plants. We observed an evident correlation between the transcript up-regulation
      and the Pro accumulation under salt stress; however, these results do not
      parallel with the changes in P5CS enzymatic activity. This Pro accumulation might
      function as an osmolyte for the intracellular osmotic adjustment and might be
      playing a critical role in protecting photosynthetic activity in O. streptacantha
      plants under salt stress.

PMID- 18054244
TI  - Increased expression of the rice C-type cyclin-dependent protein kinase gene,
      Orysa;CDKC;1, in response to salt stress.
AB  - Cyclin-dependent protein kinases (CDKs) form a conserved superfamily of
      eukaryotic serine/threonine protein kinases which require binding to a regulatory
      cyclin for activity. CDKs are organized in several gene families and are involved
      in different aspects of cell biology, such as gene transcription, cell
      proliferation and differentiation. In this study, we present the characteristics
      of the rice C-type CDK gene, Orysa;CDKC;1. The gene was expressed in all organs
      of the plant and relatively high amounts of its transcript were detected in
      mature leaves and panicles. This indicated a putative role during later stages of
      leaf and panicle development. Using yeast two-hybrid analysis, we identified
      Orysa;CYCT as an interactor with Orysa;CDKC;1. The expression profiles of the new
      Orysa;CDKC;1 in response to various factors from rice cells were compared with
      those of previously described Orysa;CDKA;1, and Orysa;CDKB2;1. The Orysa;CDKC;1
      transcript was induced by salt stress and ABA treatments, but was unaffected by
      mannitol. In addition, the MBP kinase activity associated with Orysa;CDKC;1
      immunocomplexes was induced under salt stress. We propose that Orysa;CDKC;1 may
      be involved in developmental programs, as well as in the salt- and ABA-signaling
      pathway.

PMID- 18054245
TI  - Chronic chymase inhibition preserves cardiac function after left ventricular
      repair in rats.
AB  - OBJECTIVE: Although left ventricular repair (LVR) has been widely performed, the
      initial improvement of LV function does not last because of LV remodeling. Recent
      studies have demonstrated that chymase, a local enzyme in the heart, promotes
      angiotensin II formation as well as activation of transforming growth factor
      (TGF)-beta, both of which facilitate myocardial fibrosis. Therefore, chymase
      blockade may play an important role in the prevention of cardiac remodeling after
      LVR. In this study, the effects of chronic chymase inhibition (Chy-I) after LVR
      were evaluated in a rat LV aneurysm model. METHODS: Rats that developed LV
      aneurysms 4 weeks after coronary artery ligation underwent LVR by plicating the
      LV aneurysm, and were randomized into two groups, the LVR group and the LVR + Chy
      I group that received an oral chymase inhibitor (10 mg/kg/day) for 4 weeks.
      RESULTS: Echocardiography revealed better LV function in the LVR + Chy-I group
      than in the LVR group at 4 weeks. Four weeks after LVR, LV end-diastolic pressure
      and the time constant of LV isovolumic pressure decay, were significantly lower
      in the LVR+Chy-I group. The end-systolic pressure-volume relationship was higher
      in the LVR+Chy-I group. In the LVR+Chy-I group, mRNA expressions of TGF-beta1 and
      BNP significantly decreased in the LV myocardium. Histology showed reduced
      interstitial fibrosis in the LVR+Chy-I group. CONCLUSIONS: Chronic chymase
      inhibition prevented myocardial fibrosis and preserved cardiac function after
      LVR. A chymase inhibition could be an important strategy for management after LV
      repair surgery.

PMID- 18054246
TI  - In vitro non-rigid life-size model of aortic arch aneurysm for endovascular
      prosthesis assessment.
AB  - PURPOSE: It is essential to evaluate new stent designs before in vivo testing.
      The purpose of this study was to develop and validate a controlled and
      reproducible patient-derived process to produce a life-size in vitro model of
      aortic arch aneurysm for endovascular procedure simulation. METHODS: A three
      dimensional magnetic resonance angiography (3D MRA) image derived from a 60-year
      old patient with aortic arch aneurysm was segmented using a home-made software
      package which allows one-click automatic segmentation of the aorta, meshing, and
      conversion to standard tessellation language (STL) format. A rapid prototyping
      technique established a stereolithographic model to produce a replica of the
      whole aorta, including the arch aneurysm and supra-aortic arteries. RESULTS: The
      final model was made by pouring silicone rubber to obtain a sturdy, life-size,
      soft, transparent, plastic cast, accurately reproducing both the internal and
      external anatomy of the aortic aneurysm. This model was used under perfusion by
      an extracorporeal circulation pump, to test ex vivo stent deployment. CONCLUSION:
      The combination of easy segmentation and conversion to the STL format with
      industrial stereolithography techniques enabled a realistic silicon vascular
      phantom to be created for endovascular procedure simulation, image modality
      calibration, and new stent design.

PMID- 18054247
TI  - Association of MIF-173 gene polymorphism with inflammatory bowel disease in
      Chinese Han population.
AB  - AIM: To study whether macrophage migration inhibitory factor (MIF)-173 gene
      polymorphism correlates with inflammatory bowel disease (IBD) in Chinese Han
      population. METHODS: MIF-173 single nucleotide polymorphism (SNP) was genotyped
      by tetra-primer amplification refractory mutation system (ARMS) and restriction
      fragment length polymorphisms (RFLP)-PCR in 142 healthy subjects and 98 patients
      with inflammatory bowel disease (IBD). RESULTS: There were no discrepancies
      between the results obtained by tetra-primer ARMS and RFLP-PCR. The frequency of
      MIF-173 CC genotype was significantly higher in patients with ulcerative colitis
      (UC) 15.5% than in healthy individuals 5.6% (chi(2)=6.066, P=0.018, OR=3.067 and
      95% CI=1.257-7.482). There was a trend towards a higher frequency of CC genotype
      among CD patients compared with healthy controls, however this did not attain the
      statistical significance (P=0.245). CONCLUSION: MIF-173 CC genotype may be
      associated with susceptibility to UC.

PMID- 18054248
TI  - Th17 cells and mucosal host defense.
AB  - Th17 cells are a new lineage of T-cells that are controlled by the transcription
      factor RORgammat and develop independent of GATA-3, T-bet, Stat 4 and Stat 6.
      Novel effector molecules produced by these cells include IL-17A, IL-17F, IL-22,
      and IL-26. IL-17RA binds IL-17A and IL-17F and is critical for host defense
      against extracellular planktonic bacteria by regulating chemokine gradients for
      neutrophil emigration into infected tissue sites as well as host granulopoiesis.
      Moreover, IL-17 and IL-22 regulate the production of antimicrobial proteins in
      mucosal epithelium. Although TGF-beta1 and IL-6 have been shown to be critical
      for development of Th17 cells from naive precursors, IL-23 is also important in
      regulating IL-17 release in mucosal tissues in response to infectious stimuli.
      Compared to Th1 cells, IL-23 and IL-17 show limited roles in controlling host
      defense against primary infections with intracellular bacteria such as
      Mycobacterium tuberculosis suggesting a predominate role of the Th17 lineage in
      host defense against extracellular pathogens. However, in the setting of chronic
      biofilm infections, as that occurs with cystic fibrosis or bronchiectasis, Th17
      cells may be key contributors of tissue injury.

PMID- 18054249
TI  - Applications of direct detection device in transmission electron microscopy.
AB  - A prototype direct detection device (DDD) camera system has shown great promise
      in improving both the spatial resolution and the signal to noise ratio for
      electron microscopy at 120-400 keV beam energies (Xuong et al., 2007. Methods in
      Cell Biology, 79, 721-739). Without the need for a resolution-limiting
      scintillation screen as in the charge coupled device (CCD), the DDD camera can
      outperform CCD based systems in terms of spatial resolution, due to its small
      pixel size (5 microm). In this paper, the modulation transfer function (MTF) of
      the DDD prototype is measured and compared with the specifications of commercial
      scientific CCD camera systems. Combining the fast speed of the DDD with image
      mosaic techniques, fast wide-area imaging is now possible. In this paper, the
      first large area mosaic image and the first tomography dataset from the DDD
      camera are presented, along with an image processing algorithm to correct the
      specimen drift utilizing the fast readout of the DDD system.

PMID- 18054250
TI  - Synchrotron microComputed Tomography of the mature bovine dentinoenamel junction.
AB  - The mature dentinoenamel junction (DEJ) is viewed by some investigators and the
      current authors, not as a fossilized, sharp transition between enamel and dentin,
      but as a relatively broad structural transition zone including the mantle dentin
      and the inner aprismatic enamel. In this study, the DEJ structure in bovine
      incisors was studied with synchrotron microComputed Tomography (microCT) using
      small cubes cut parallel to the tooth surface. The reconstructions revealed a
      zone of highly variable punctate contrast between bulk dentin and enamel; the
      mean linear attenuation coefficients and their standard deviations demonstrated
      that this zone averaged less mineral than dentin or enamel but had more highly
      variable structure than either. The region with the punctuate contrast is,
      therefore, the mantle dentin. The thickness of the mantle dentin seen in a
      typical data set was about 30 microm, and the mantle dentin-enamel interface
      deviated +/-15 microm from the average plane over a distance of 520 microm. In
      the highest resolution data ( approximately 1.5 microm isotropic voxels, volume
      elements), tubules in the dentin could be discerned in the vicinity of the DEJ.
      Contrast sensitivity was high enough to detect differences in mineral content
      between near-surface and near-DEJ volumes of the enamel. Reconstructions before
      and after two cubes were compressed to failure revealed cracks formed only in the
      enamel and did not propagate across the mantle dentin, regardless of whether
      loading was parallel to or perpendicular to the DEJ.

PMID- 18054252
TI  - Source of nonlinearity of the BOLD response revealed by simultaneous fMRI and
      NIRS.
AB  - The nonlinearity of the blood oxygenation level-dependent (BOLD) response to
      stimuli of different duration, particularly those of short duration, has been
      well studied by functional magnetic resonance imaging (fMRI). This nonlinearity
      is assumed to be due to neural adaptation and the nonlinearity of the response in
      the oxygen extraction fraction (OEF); the latter has not been examined
      quantitatively in humans. To evaluate how the OEF response contributes to the
      nonlinearity of the BOLD response to neural activity, we used simultaneous fMRI
      and near-infrared spectroscopy (NIRS). The responses to visual stimuli of four
      different durations were measured as changes in the BOLD signal and the NIRS
      derived hemoglobin concentrations. The hemodynamic response nonlinearity was
      quantified using an impulse response function model with saturation nonlinearity
      scaling in the response amplitude, assuming that the unknown neural adaptation
      parameters varied within a physiologically feasible range. Independent of the
      degree of neural adaptation, the BOLD response consistently showed saturation
      nonlinearity similar to that of the OEF response estimated from the NIRS
      measures, the nonlinearity of which was greater than that of the response in the
      total hemoglobin concentration representing the cerebral blood volume (CBV). We
      also found that the contribution of the OEF response to the BOLD response was
      four to seven times greater than the contribution of the CBV response. Thus, we
      conclude that the nonlinearity of the BOLD response to neural activity originates
      mainly from that of the OEF response.

PMID- 18054251
TI  - Shining new light on the brain's "bilingual signature": a functional Near
      Infrared Spectroscopy investigation of semantic processing.
AB  - Decades of research have shown that, from an early age, proficient bilinguals can
      speak each of their two languages separately (similar to monolinguals) or rapidly
      switch between them (dissimilar to monolinguals). Thus we ask, do monolingual and
      bilingual brains process language similarly or dissimilarly, and is this affected
      by the language context? Using an innovative brain imaging technology, functional
      Near Infrared Spectroscopy (fNIRS), we investigated how adult bilinguals process
      semantic information, both in speech and in print, in a monolingual language
      context (one language at a time) or in a bilingual language context (two
      languages in rapid alternation). While undergoing fNIRS recording, ten early
      exposed, highly proficient Spanish-English bilinguals completed a Semantic
      Judgment task in monolingual and bilingual contexts and were compared to ten
      English monolingual controls. Two hypotheses were tested: the Signature
      Hypothesis predicts that early, highly proficient bilinguals will recruit neural
      tissue to process language differently from monolinguals across all language
      contexts. The Switching Hypothesis predicts that bilinguals will recruit neural
      tissue to process language similarly to monolinguals, when using one language at
      a time. Supporting the Signature Hypothesis, in the monolingual context,
      bilinguals and monolinguals showed differences in both hemispheres in the
      recruitment of DLPFC (BA 46/9) and IFC (BA 47/11), but similar recruitment of
      Broca's area (BA 44/45). In particular, in the monolingual context, bilinguals
      showed greater signal intensity in channels maximally overlaying DLPFC and IFC
      regions as compared to monolinguals. In the bilingual context, bilinguals
      demonstrated a more robust recruitment of right DLPFC and right IFC. These
      findings reveal how extensive early bilingual exposure modifies language
      organization in the brain-thus imparting a possible "bilingual signature." They
      further shed fascinating new light on how the bilingual brain may reveal the
      biological extent of the neural architecture underlying all human language and
      the language processing potential not fully recruited in the monolingual brain.

PMID- 18054253
TI  - Alzheimer's disease diagnosis in individual subjects using structural MR images:
      validation studies.
AB  - OBJECTIVE: To develop and validate a tool for Alzheimer's disease (AD) diagnosis
      in individual subjects using support vector machine (SVM)-based classification of
      structural MR (sMR) images. BACKGROUND: Libraries of sMR scans of clinically well
      characterized subjects can be harnessed for the purpose of diagnosing new
      incoming subjects. METHODS: One hundred ninety patients with probable AD were age
      and gender-matched with 190 cognitively normal (CN) subjects. Three different
      classification models were implemented: Model I uses tissue densities obtained
      from sMR scans to give STructural Abnormality iNDex (STAND)-score; and Models II
      and III use tissue densities as well as covariates (demographics and
      Apolipoprotein E genotype) to give adjusted-STAND (aSTAND)-score. Data from 140
      AD and 140 CN were used for training. The SVM parameter optimization and training
      were done by four-fold cross validation (CV). The remaining independent sample of
      50 AD and 50 CN was used to obtain a minimally biased estimate of the
      generalization error of the algorithm. RESULTS: The CV accuracy of Model II and
      Model III aSTAND-scores was 88.5% and 89.3%, respectively, and the developed
      models generalized well on the independent test data sets. Anatomic patterns best
      differentiating the groups were consistent with the known distribution of
      neurofibrillary AD pathology. CONCLUSIONS: This paper presents preliminary
      evidence that application of SVM-based classification of an individual sMR scan
      relative to a library of scans can provide useful information in individual
      subjects for diagnosis of AD. Including demographic and genetic information in
      the classification algorithm slightly improves diagnostic accuracy.

PMID- 18054254
TI  - Molecular phylogeny and historical biogeography of the Holarctic wetland leaf
      beetle of the genus Plateumaris.
AB  - Leaf beetles of the genus Plateumaris inhabit wetlands across the temperate zone
      of the Holarctic region. To explore the phylogeographic relationships among North
      American, East Asian, and European members of this genus and the origin of the
      species endemic to Japan, we studied the molecular phylogeny of 20 of the 27
      species in this genus using partial sequences of mitochondrial cytochrome oxidase
      subunit I (COI) and the 16S and nuclear 28S rRNA genes. The molecular phylogeny
      revealed that three species endemic to Europe are monophyletic and sister to the
      remaining 11 North American and six Asian species. Within the latter clade, North
      American and Asian species did not show reciprocal monophyly. Dispersal
      vicariance analysis and divergence time estimation revealed that the European and
      North America-Asian lineages diverged during the Eocene. Moreover, subsequent
      differentiation occurred repeatedly between North American and Asian species,
      which was facilitated by three dispersal events from North America to Asia and
      one in the opposite direction during the late Eocene through the late Miocene.
      Two Japanese endemics originated from different divergence events; one
      differentiated from the mainland lineage after differentiation from the North
      American lineage, whereas the other showed a deep coalescence from the North
      American lineage with no present-day sister species on the East Asian mainland.
      This study of extant insects provides molecular phylogenetic evidence for ancient
      vicariance between Europe and East Asia-North America, and for more recent (but
      pre-Pleistocene) faunal exchanges between East Asia and North America.

PMID- 18054255
TI  - Differential effects of tumor necrosis factor-alpha and interleukin-1beta on cell
      death in human articular chondrocytes.
AB  - OBJECTIVE: The death of chondrocytes by apoptosis is characteristic of
      degenerative joint diseases, such as osteoarthritis (OA). Tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1beta (IL-1beta) have been shown to play an
      important role in the development of OA. In this study we analyzed the effects of
      TNF-alpha and IL-1beta on cell death in normal human chondrocytes. METHODS:
      Normal human chondrocytes were isolated from knee cartilage obtained at autopsy
      from 30 adult cadaveric donors. The cells were stimulated with TNF-alpha (10
      ng/ml) or IL-1beta (5 ng/ml) in the presence or absence of Ro 31-8220 (Ro: a
      structurally related analog of bisindolylmaleimide that inhibits mitogen
      activated protein kinase phosphatase 1 [MKP-1]) (Ro; 10 microM), an MKP-1
      inhibitor, which induces apoptosis in chondrocytes. Apoptosis was evaluated by
      flow cytometry (propidium iodide) and nuclear morphology was evaluated with 4',6'
      dianidino-2-phenylindole dihydrochloride. The expressions of caspase-8, -7 and -3
      and Bcl-2 were analyzed by Western blot and the activation of caspase-3 and -8
      was measured by flow cytometry. Prostaglandin E2 (PGE2) was evaluated by enzyme
      linked immunosorbent assay. RESULTS: At 24 h the percentage of apoptotic
      (hypodiploid) nuclei induced by TNF-alpha+Ro was higher than the level induced by
      Ro alone. The combination of IL-1beta (5 ng/ml) with Ro did not show a
      synergistic effect. A morphological analysis demonstrated that treatment with TNF
      alpha+Ro resulted in a large number of cells with condensed nuclei and DNA
      fragmentation. Western blot studies indicated that IL-1beta+Ro did not induce the
      time-dependent activation of caspase-8, -7 and -3 as seen with TNF-alpha+Ro. As
      quantified by flow cytometry, TNF-alpha+Ro induced a higher level of caspase-3
      and -8 activation than that seen with IL-1beta+Ro. Pre-incubation for 2h with
      caspase inhibitors for caspase-3, -7, -8 and pan-caspase significantly decreased
      the hypodiploid DNA peak induced by treatment with TNF-alpha+Ro at 24 h.
      Indomethacin increased the cell death induced by IL-1beta+Ro; however, apoptosis
      induced by TNF-alpha+Ro was not modified by indomethacin. CONCLUSIONS: These
      results confirm that TNF-alpha and IL-1beta regulate apoptosis differently in
      this human chondrocyte model and that the differing effects of these cytokines
      are PGE2-independent. Indomethacin potentiates the effect of IL-1 on cell death
      and this may explain the reported effect of indomethacin on the progression of
      joint destruction.

PMID- 18054256
TI  - Intrahippocampal anisomycin infusions disrupt previously consolidated spatial
      memory only when memory is updated.
AB  - Reconsolidation has proven to be a common phenomenon relevant to memory
      processing. However, the functional significance of this process is still a
      matter of debate. Previous work has shown that reconsolidation is indeed a
      process by which updated information is integrated, through the synthesis of
      proteins, to a memory trace. To further analyze the role that updated information
      plays in retrieved spatial memory susceptibility to disruption, we injected
      anisomycin bilaterally in the dorsal hippocampus of Wistar rats. Implanted
      animals were trained for 5 days on the Morris water maze (MWM) task and injected
      with anisomycin before the third or fifth training session. When memory was
      assessed a week later, only animals injected on the third training session showed
      disruption of long-term memory. Furthermore, when animals were trained for either
      3 (middle-trained) or 5 (well-trained) days and a week later anisomycin was
      infused before a reminder session, only middle-trained rats infused with
      anisomycin showed reduced performance when tested for long-term memory. Finally,
      animals trained for 5 days and injected with anisomycin 7 days later on an
      extinction session showed impaired long-term extinction when tested. These
      results suggest that for spatial memory tasks acquisition of updated information
      is a necessary feature to undergo this process. We propose that reconsolidation
      is not an accurate term because it implies that consolidation happens again. This
      conception does not fit with the evidence; hence, we suggest that updating
      consolidation is a more descriptive term to refer to this process.

PMID- 18054257
TI  - Differential effects of inactivation of the orbitofrontal cortex on strategy set
      shifting and reversal learning.
AB  - Different subregions of the rodent prefrontal cortex (PFC) mediate dissociable
      types of behavioral flexibility. For example, lesions of the medial or
      orbitofrontal (OFC) regions of the PFC impair extradimensional shifts and
      reversal learning, respectively, when novel stimuli are used during different
      phases of the task. In the present study, we assessed the effects of inactivation
      of the OFC on strategy set-shifting and reversal learning, using a maze based set
      shifting task mediated by the medial PFC. Long-Evans rats were trained initially
      on a visual-cue discrimination to obtain food. On the subsequent day, rats had to
      shift to using a response strategy (e.g., always turn left). On Day 3 (reversal),
      rats were required to reverse the direction of their turn (e.g., always turn
      right). Infusions of the local anesthetic bupivacaine into the OFC did not impair
      initial visual discrimination learning, nor did it impair performance on the set
      shift. In contrast, inactivation of the OFC did impair reversal learning; yet,
      these rats ceased using the previously acquired response rule as readily as
      controls. Instead, rats receiving OFC inactivations made a disproportionate
      number of erroneous arm entries towards the visual-cue, suggested that these
      animals reverted back to using the original visual-cue based strategy. These
      findings, in addition to previous data, further support the notion that the OFC
      and medial PFC play dissociable roles in reversal learning and set-shifting.
      Furthermore, the lack of effect of OFC inactivations on the set-shift indicates
      that this type of behavioral flexibility does not require cognitive operations
      related to reversal learning.

PMID- 18054258
TI  - Plasma lipids are altered in Gaucher disease: biochemical markers to evaluate
      therapeutic intervention.
AB  - Enzyme replacement therapy has been in clinical practice for the non
      neuronopathic form of Gaucher disease for 15 years. However, the wide phenotypic
      variability in this disorder poses challenges to clinicians to assess patient
      severity and disease progression in order to effectively manage patients. Once
      therapy is initiated, methods to monitor the complex biochemical changes
      associated with the disease, and the response of these changes to therapy, are
      required in order to tailor therapy regimens to individual patients. We have
      evaluated the suitability of plasma sphingolipids and phospholipids as
      biochemical markers of disease burden and the efficacy of therapy to reduce that
      burden. Over 60 lipid species were measured using electrospray ionization-tandem
      mass spectrometry in plasma from controls and Gaucher patients, pre- and post
      therapy. Glucosylceramide, molecular species of phosphatidylglycerol and G(M3)
      ganglioside were elevated in Gaucher disease, whereas species of ceramide,
      dihexosylceramide and sphingomyelin were decreased. Multivariate analysis enabled
      us to calculate the combined response of these lipids to therapy in Gaucher
      patients and correlate them with patient severity. Plasma lipids are proposed to
      be useful biomarkers for Gaucher disease.

PMID- 18054259
TI  - Airway evaluation in obstructive sleep apnea.
AB  - As the interest in sleep-disordered breathing has increased, various attempts
      have been made to assess upper airway anatomy in patients with this relatively
      frequent disorder. The aim is not only to reveal potential differences in upper
      airway anatomy to better understand origin and pathophysiology of the disease but
      also to improve patient management and treatment success. The present review is
      based on a systematic literature search with regard to upper airway evaluation in
      sleep-disordered breathing; the articles were selected and discussed in light of
      our clinical experiences. Based on clinical assessment including endoscopy during
      wakefulness, the value of the Mueller Maneuver, static radiologic imaging
      techniques (X-ray cephalometry, computed tomography (CT) scanning and magnetic
      resonance imaging (MRI)), dynamic scanning protocols (e.g. ultrafast CT or cine
      MRI), upper airway endoscopy during sleep and sedated sleep, pressure
      measurements and the assessment of the critical closing pressure are discussed.
      Each technique itself and its history in the field of sleep medicine are briefly
      reviewed and problems of standardization and interpretation are discussed when
      appropriate. Insights into the pathophysiology of the disease gained with the
      help of the investigational techniques are presented and the impact of the
      techniques on patient management is reported. Although all these additional
      techniques for upper airway assessment have substantially improved our
      understanding of sleep-disordered breathing, their significance in daily practice
      is limited. In contrast to the widespread use of the Mueller maneuver and sedated
      endoscopy, convincing data supporting their use in terms of treatment outcome are
      lacking. So far, there is only very limited evidence that selected techniques
      improve treatment outcome for selected indications. In general, there is not
      enough evidence that these techniques are superior to the routine clinical
      assessment.

PMID- 18054261
TI  - High density and food deprivation affect arginine vasotocin, isotocin and
      melatonin in gilthead sea bream (Sparus auratus).
AB  - Arginine vasotocin (AVT) and isotocin (IT) levels in plasma and pituitary, and
      melatonin (MEL) levels in plasma were determined in gilthead sea bream (Sparus
      auratus) subjected to two different types of stress: i) high density (HD) and ii)
      food deprivation (NF: non-fed). Fishes were randomly assigned to one of 4
      treatments that lasted for 14 days: 1) fed fish under normal low density (ND, 4
      kg m(-3)); 2) non-fed (NF) fish under ND; 3) fed fish under high density (HD, 70
      kg m(-3)); and 4) non-fed fish under HD. Ten fish from each tank were
      anaesthetized, weighed and plasma and pituitary samples were taken. Plasma and
      pituitary AVT and IT content were determined by HPLC, while plasma MEL was
      assayed by RIA. Plasma AVT and IT values were enhanced in all fish kept at high
      density. The response of AVT was much stronger than that of IT. The highest
      pituitary AVT and IT levels were shown in NF fish kept at normal density. The
      significantly higher plasma MEL levels were measured in fed fish kept at HD.
      These results suggest a role of AVT, IT and MEL in response of sea bream to a
      common stress factor, high density. Although food deprivation does not influence
      AVT and IT plasma levels, it seems to affect hypothalamic synthesis of
      nonapeptides. Further studies are required to elucidate the complex role of AVT,
      IT and MEL in the sea bream's response to different stress stimuli.

PMID- 18054262
TI  - [Imaging of the Alzheimer's disease: MRI and functional imaging].
AB  - The MRI is often the initial exploration proposed to a patient presenting a
      confusion of memory. This examination has for purpose first to eliminate surgical
      differential diagnoses, such as a chronic hydrocephalus of the adult. It can then
      help in the differential diagnosis between the various insane syndromes, like
      Alzheimer's disease.

PMID- 18054260
TI  - The pharmokinetic limitations of antioxidant treatment for COPD.
AB  - COPD is one of the leading causes of death worldwide and the age-adjusted
      mortality for this disease has risen significantly over the past 30 years.
      Current pharmacological treatments do not effectively address the inflammatory
      and apoptotic mechanisms that are critical in the development of this disease.
      Thus, despite therapy, patients typically experience a continued deterioration of
      their clinical status. Markers of oxidative stress are increased in the lungs of
      COPD patients and epidemiologic and animal studies indicate that antioxidants can
      protect the lungs from the damaging effects of cigarette smoke. To date, however,
      clinical trials of antioxidants for COPD have yielded disappointing results. This
      review discusses the pharmokinetic factors that limit the use of exogenous
      antioxidants as a treatment for this disease. In addition, it addresses
      strategies to overcome these limitations so that the beneficial properties of
      antioxidants can be translated into effective therapies for COPD patients.

PMID- 18054263
TI  - [Molecular and therapeutic approaches of the Alzheimer's disease].
AB  - The Alzheimer's disease (AD) is clinically characterized by the progressive
      appearance of amnesic disorders, which are followed by a clinical syndrome
      associating aphasia, apraxia and agnosia. In this picture are added behavioural
      problems, marked for example by decision-making or judgment confusions and
      disturbances of the orientation. The therapeutic perspectives are based
      especially on molecular targets that are the peptide Abeta, the protein tau or
      the facilitating molecular ways of neurodegeneration.

PMID- 18054264
TI  - [Epidemiology of vulvar intra-epithelial neoplasias].
AB  - The vulvar intraepithelial neoplasia has been identified as one of the 12
      neoplasias whose incidence increases in the developed countries. The vulvar
      intraepithelial neoplasia (VIN) and invasive vulvar cancer incidence increases by
      2.4% per annum; and this principally in young women. The VIN account for 57% of
      the vulvar neoplasias and are actually more frequent than invasive carcinomas. In
      the United States, between 1973 and 2000, the incidence of the VIN increased by
      411% against 20% for invasive cancers. Similar figures were reported from
      Norwegian registers. The VIN have a different age distribution than invasive
      cancers: the incidence of the VIN increases until the age of 40-49 years then
      decreases while the incidence of invasive cancers increases after 50 years
      without real peak of incidence. The increase in the incidence of VIN could be
      followed by an increase in the incidence of invasive cancers but the unknowns on
      the natural history of the VIN and the impact of the treatments make any
      extrapolation hazardous. The association between the VIN and the human
      papillomavirus (HPV) has been well established. It should be noted that, contrary
      to the cervical neoplasia that are related for nearly 100% to the HPV, only 30
      40% of invasive cancers of the vulva are related to HPV, while the other
      carcinomas are related to the evolution of a vulvar lichen sclerous. The HPV
      induce various types of anogenital lesion according to their genotype. These
      lesions can be benign for the HPV6 and 11 and preneoplastic or neoplastic for the
      HPV16 and 18. The presence of HPV16 and 18 is found in 70 to 80% of the VIN
      suggesting that HPV vaccines could decrease the incidence VIN and HPV related
      invasive vulvar cancer.

PMID- 18054265
TI  - [Role of homeopathy in gynecology].

PMID- 18054266
TI  - Sonophotoelectrocatalytic degradation of azo dye on TiO2 nanotube electrode.
AB  - The degradation of azo dye, methyl orange (MeO) in aqueous solution with
      sonophotoelectrocatalytic process was investigated. The TiO(2) nanotubes were
      used as electrode in photoelectrocatalytic (PEC), sonophotoelectrocatalytic
      (SPEC) processes or as photocatalyst in photocatalytic (PC), sonophotocatalytic
      (SPC) processes, respectively. Experimental results showed that the hybrid
      processes could efficiently enhance the degradation efficiency of MeO, and
      followed pseudo-first-order kinetics. At the optimized experimental conditions,
      the rate constants of decolorization of MeO were 0.0732 min(-1) for SPEC process;
      0.0523 min(-1) for PEC process, 0.0073 min(-1) for SPC process and 0.0035 min(-1)
      for PC process. The rate constants obviously indicated that there existed
      synergistic effect in the ultrasonic, electro-assisted and photocatalytic
      processes.

PMID- 18054267
TI  - Targeting of dystroglycan to the cleavage furrow and midbody in cytokinesis.
AB  - Dystroglycan is a cell adhesion molecule that interacts with ezrin family
      proteins and also components of the extracellular signal-regulated kinase
      pathway. Ezrin and extracellular signal-regulated kinase are both involved in
      aspects of the cell division cycle. We therefore examined the role of
      dystroglycan during cytokinesis. Endogenous dystroglycan colocalised with ezrin
      at the cleavage furrow and midbody during cytokinesis in REF52 cells. Live cell
      imaging of green fluorescent protein-tagged dystroglycan in Swiss 3T3 and Hela
      cells revealed a similar localisation. Live cell imaging of a dystroglycan
      lacking its cytoplasmic domain revealed an even membrane localisation but no
      cleavage furrow or midbody localisation. Deletion of a previously identified
      ezrin-binding site in the dystroglycan cytoplasmic domain however only resulted
      in a slight reduction in cleavage furrow localisation but loss of midbody
      staining. There was no apparent cytokinetic defect in cells depleted for
      dystroglycan, however apoptosis levels were considerably higher in dystroglycan
      knockdown cells. Cell cycle analysis showed a delay in G2/M transition, possibly
      caused by a more than 50% reduction in extracellular signal-regulated kinase
      levels in the knockdown cells. Dystroglycan may therefore not only have a role in
      organising the contractile ring through direct or indirect associations with
      actin, but can also modulate the cell cycle by affecting extracellular signal
      regulated kinase levels.

PMID- 18054268
TI  - Hydrogen peroxide stimulates tetrahydrobiopterin synthesis through activation of
      the Jak2 tyrosine kinase pathway in vascular endothelial cells.
AB  - Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase
      (NOS). We previously described that hydrogen peroxide (H(2)O(2)) increases BH4
      levels through the induction of GTP-cyclohydrolase I (GTPCH), which is the rate
      limiting enzyme for the synthesis of BH4, in vascular endothelial cells. The aim
      of this study was to examine the underlying mechanism of H(2)O(2)-induced BH4
      synthesis in vascular endothelial cells. The increases in BH4 levels induced by
      H(2)O(2) were strongly reduced by a Janus kinase-2 (Jak2) inhibitor, AG490. The
      H(2)O(2)-induced increases in GTPCH mRNA expression and GTPCH activity were also
      blocked by treatment with AG490. H(2)O(2) elicited an increase in the level of
      phosphorylated Jak2, suggesting that the induction of BH4 by H(2)O(2) was
      mediated by the Jak2 pathway. Signal transducers and activators of transcription
      (Stats) are the best-known substrates for Jak2. The H(2)O(2)-induecd increases in
      BH4 levels were reduced by treatment with fludarabine, which is shown to cause a
      specific depletion of Stat1 protein but not of other Stats. Moreover, H(2)O(2)
      caused the DNA binding of Stat1, and this was inhibited by AG490. Stat1
      phosphorylation was enhanced by H(2)O(2) treatment, and the phosphorylation was
      attenuated by AG490. These findings suggest that the stimulation of BH4 synthesis
      through the induction of GTPCH is mediated at least in-part by the Jak2-Stat1
      pathway.

PMID- 18054269
TI  - Ginkgolides mimic the effects of hypoxic preconditioning to protect C6 cells
      against ischemic injury by up-regulation of hypoxia-inducible factor-1 alpha and
      erythropoietin.
AB  - Hypoxic preconditioning can play a significant neuroprotective role. However, it
      has not been employed clinically because of safety concerns. To find a safer
      preconditioning stimulus that is both practical and effective, we investigated
      whether ginkgolides are capable of preconditioning as hypoxia to protect C6 cells
      against ischemic injury. We demonstrated that both ginkgolides (37.5microg/mL)
      and hypoxia (1% O(2) for 16h) can significantly increase cell viabilities and
      expression of phosphorylated glycogen synthase kinase (p-GSK), phosphorylated
      extracellular signal-regulated kinase (p-ERK), hypoxia-inducible factor-1 alpha
      (HIF-1alpha) and erythropoietin (EPO) in ischemic cells. The inhibitors of
      mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3'-kinase (PI3K)
      significantly but not completely reduced the enhanced expression of these
      proteins and cell viabilities induced by ginkgolides and hypoxic preconditioning.
      These indicated that ginkgolides could mimic hypoxic preconditioning by
      increasing expression of HIF-1alpha as well as its target protein EPO and that
      the ginkgolides and hypoxic preconditioning role might be partly mediated by the
      activation of the p42/p44-mitogen-activated protein kinase and
      phosphatidylinositol 3'-kinase/AKT/glycogen synthase kinase 3beta pathways. The
      similar tendency in the changes of protein expression, cell viabilities and
      responses to MAPK or PI3K inhibitors of the cells treated with ginkgolides and
      hypoxia suggests that ginkgolides and hypoxic preconditioning might operate by
      similar mechanisms. The findings also imply that ginkgolides might have the
      potential for clinical use to prevent injury in high-risk conditions.

PMID- 18054270
TI  - Investigating oxidative DNA damage and its repair using the comet assay.
AB  - The comet assay is not the only way to measure oxidative DNA damage, but it is
      one of the most sensitive and accurate, being relatively free of artefacts. It is
      a valuable tool in population monitoring, for example in assessing the role of
      oxidative stress in human disease, and in monitoring the effects of dietary
      antioxidants. A simple modification allows the measurement of DNA repair. In
      combination with the analysis of polymorphisms in relevant genes, the comet assay
      - especially when adapted for analysis of large numbers of samples - can provide
      important information on the interactions between genetic variation and
      environmental factors in maintaining genome stability.

PMID- 18054271
TI  - Investigation on the binding of TNS to centrin, an EF-hand protein.
AB  - The interaction between 2-p-toluidinylnaphthalene-6-sulfonate (TNS) and ciliate
      Euplotes Octocarinatus centrin (Cen) has been studied by fluorescence
      spectroscopy. The binding constants of TNS with Cen were measured at different
      temperature in the 0.01M Hepes, pH 7.4. The binding process is exothermic and
      involves a positive entropy change. The negative value of enthalpy predominately
      contributes to the negative free energy of binding between TNS and Cen. The salt
      (KCl) increases the association constant of TNS and Cen. These results and
      resonance light scattering experiment suggest that the binding force between TNS
      and Cen is hydrophobic. The distance (r) between TNS and tryptophan of mutant
      G115W, which sheds more insight into the binding of TNS to Cen, was determined as
      4.85nm based on Forster non-radiative energy transfer theory.

PMID- 18054272
TI  - The aggregation of the merocyanine dyes, depending of the type of the
      counterions.
AB  - Counterions affect on the substructures formation in the case of the merocyanine
      dye, 1-methyl-4-[2-(4-hydroxyphenyl)ethenyl)]piridinium] hydrogensquarate both in
      gas and condense phase. Spectroscopically and structural elucidation of these
      aggregates have been performed, using solid-state conventional and linear
      polarized IR-spectroscopy of oriented colloids as a nematic liquid crystal
      suspension, UV-vis spectroscopy, HPLC tandem ESI mass spectrometry, 1H and 13C
      NMR, TGV and DSC. Quantum chemical DFT calculations have been carried out as
      well. Experimental and theoretical data are compared with analogous ones of
      corresponding iodide salt of dye studied.

PMID- 18054273
TI  - The subtle electronic effects of alkyl groups on the conformational equilibria
      and intramolecular hydrogen-bond strength in cis-3-alkoxycyclohexanols.
AB  - 1H NMR data for cis-3-n-propoxycyclohexanol (cis-3-PCH) and cis-3-isopropoxy
      cyclohexanol (cis-3-ICH) show that a concentration increase shifts the
      conformational equilibrium from the diaxial (aa) conformer, stabilized by an
      intramolecular hydrogen bond (IAHB), to the diequatorial (ee) conformer [Xee=42%
      and 21% (at 0.01 mol L(-1)) to 58% and 56% (at 0.40 mol L(-1)), in CCl4,
      respectively] due to intermolecular hydrogen bonds (IEHB), as confirmed by IR
      data. The Deltanu values, obtained by IR spectra, indicated that increasing the
      size of the OR group [R=CH3, CH2CH2CH3 and CH(CH3)2], increases the IAHB
      strength, due to an increase in the inductive effect of R group, which makes the
      oxygen lone pairs more available for an IAHB with OH group, in opposition to the
      steric effect. The percentage of ee conformer increases with the solvent basicity
      for cis-3-PCH and cis-3-ICH, from 48% and 36% in CCl(4) to 97% and 96% in DMSO,
      respectively. Values of 4.58, 6.06 and 6.33 kcal mol(-1) for the IAHB strength in
      cis-3-PCH, cis-3-ICH and cis-3-TCH (cis-3-tert-butoxycyclohexanol), respectively,
      were obtained, from the theoretical data through the CBS-4M method, confirming
      the experimental results and indicating that the IAHB strength increases with the
      increasing bulk of OR substituent in this series of compounds.

PMID- 18054274
TI  - Characterization of melittin binding to Euplotes octocarinatus centrin.
AB  - In the presence of 1.0mM Ca2+, the interaction between Euplotes octocarinatus
      centrin (EoCen) and melittin (ME) was studied by means of fluorescence spectra.
      In 0.1M N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (Hepes) and 150mM NaCl
      at pH 7.4, fluorescence peak of ME was observed at about 353nm indicating that
      micro-environment of Tryptophan (Trp) residue in ME was hydrophilic. With the
      addition of 3.2x10(-4)M calcium saturated EoCen (holoEoCen), the peak of ME was
      blue-shifted to 339nm, which may be resulted from micro-environmental changes of
      the peptide. At the same time, fluorescence emission of ME was increased
      significantly suggesting that new complex of ME-holoEoCen was formed under the
      experimental conditions. Based on the fluorescence titration curves, the 1:1
      stoichiometric ratio of holoEoCen to ME was confirmed. In addition, the
      conditional binding constant of holoEoCen with ME was calculated to be logKME
      holoEoCen=6.59+/-0.14.

PMID- 18054275
TI  - Impact of electronic prescribing in a hospital setting: a process-focused
      evaluation.
AB  - OBJECTIVE: To evaluate effects of a natural CPOE implementation in a hospital
      setting and inform the efficacy of using CPOE rather than traditional paper
      medication orders. DESIGN: A multiple-baseline, quasi-experimental study of a
      naturally occurring CPOE intervention, with a non-equivalent control site.
      MEASUREMENTS: Compliance with medication-ordering protocols and time to first
      dose of antibiotics. RESULTS: Medication orders placed using CPOE were
      significantly more compliant than paper-based medication orders, and first doses
      of antibiotics were delivered significantly faster when ordered with CPOE than
      when placed using the standard paper-based system (p<.01). CONCLUSION: Findings
      support the use of CPOE and justify the need for interventions to increase CPOE
      adoption and consistent use among physicians.

PMID- 18054276
TI  - Herpetic tracheitis and polybacterial pneumonia in an immunocompetent young man
      is herpes tracheitis involved in the pathogenesis of bacterial pneumonia?
AB  - We report a 28-year-old immunocompetent man that after a course of corticoids
      developed a severe pneumonia in right lower lobe. A fiber-optic bronchoscopy
      showed a white membrane easily bloody on contact with bronchoscopy tube at
      trachea level. The tracheal biopsy showed typical cytopathological lesions of
      herpes simplex virus (HSV) and polymerase chain reaction was positive for type 1
      HSV. Streptococcus viridans and Fusobacterium necrophorum grew in right bronchial
      secretion cultures. Clinical improvement was achieved after prolonged antibiotic
      therapy and before initiating treatment with acyclovir. Herpetic tracheitis could
      have been involved in the aspiration of oropharyngeal material that leaded to the
      development of this bacterial pneumonia.

PMID- 18054277
TI  - Distribution of hepatitis C virus (HCV) genotypes among HCV infection risk groups
      in Lebanon.

PMID- 18054278
TI  - Slow pattern-reversal stimulation facilitates the assessment of retinal function
      with multifocal recordings.
AB  - OBJECTIVE: The use of the multifocal pattern electroretinogram (mfPERG) for
      objective visual field testing is critically impaired by the small signal-to
      noise ratios (SNRs) obtained. In order to explore ways to enhance mfPERG-SNRs and
      mfPERG-magnitude, the dependence of mfPERGs and multifocal visual evoked
      potentials (mfVEPs) on stimulation rate and stimulation mode is examined.
      METHODS: Using VERIS Science 5.1.10X (EDI, CA, USA) mfPERGs and mfVEPs were
      recorded simultaneously in two different experiments to stimulation at 52
      locations comprising a visual field of 44 degrees diameter. Firstly, in eight
      subjects the response magnitudes were compared for three pattern-reversal (PR)
      and two pattern-onset (PO) stimulus conditions, which differed in their maximal
      stimulation rate. Secondly, for equal recording durations the signal-to-noise
      ratios (SNRs) of four PR stimuli with different stimulation rates were determined
      in eight subjects. RESULTS: Both mfPERG and mfVEP response magnitudes were
      substantially enhanced for the lower stimulation rates. The greatest effects were
      obtained for the mfPERG-N95 to pattern-reversal stimulation, which was by a
      factor of 5.2+/-0.6 greater than that N95 for the standard condition (p<0.001).
      mfPERGs for a comparatively low stimulation rate, i.e., reversing its contrast
      with a probability of 50% only every 53 ms, yielded the greatest SNRs (1.42-fold
      greater than for the standard condition; p<or=0.002). CONCLUSIONS: The
      enhancement of both mfPERG and mfVEP response magnitudes for slow stimulation
      suggests that retinal mechanisms contribute to this response enhancement and that
      slow pattern-reversal stimulation might facilitate simultaneous high-resolution
      mfPERG- and mfVEP-based visual field testing. SIGNIFICANCE: The study suggests
      that mfPERG-based assessment of retinal ganglion cell function can be improved
      with stimulation sequences that are 2-4 times slower than the standard multifocal
      stimulus.

PMID- 18054279
TI  - Event-related wave activity in the EEG provides new marker of ADHD.
AB  - OBJECTIVE: This study examines the utility of new measures of event-related
      spatio-temporal waves in the EEG as a marker of ADHD, previously shown to be
      closely related to the P3 ERP in an adult sample. METHODS: Wave activity in the
      EEG was assessed during both an auditory Oddball and a visual continuous
      performance task (CPT) for an ADHD group ranging in age from 6 to 18 years and
      comprising mostly Combined and Inattentive subtypes, and for an age and gender
      matched control group. RESULTS: The ADHD subjects had less wave activity at low
      frequencies ( approximately 1 Hz) during both tasks. For auditory Oddball
      targets, this effect was shown to be related to smaller P3 ERP amplitudes. During
      CPT, the approximately 1 Hz wave activity in the ADHD subjects was inversely
      related to clinical and behavioral measures of hyperactivity and impulsivity. CPT
      wave activity at approximately 1 Hz was seen to "normalise" following treatment
      with stimulant medication. CONCLUSIONS: The results identify a deficit in low
      frequency wave activity as a new marker for ADHD associated with levels of
      hyperactivity and impulsivity. SIGNIFICANCE: The marker is evident across a range
      of tasks and may be specific to ADHD. While lower approximately 1 Hz activity
      partly accounts for reduced P3 ERPs in ADHD, the effect also arises for tasks
      that do not elicit a P3. Deficits in behavioral inhibition are hypothesized to
      arise from underlying dysregulation of cortical inhibition.

PMID- 18054280
TI  - Unmasking of presynaptic and postsynaptic high-frequency oscillations in epidural
      cervical somatosensory evoked potentials during voluntary movement.
AB  - OBJECTIVE: To investigate the effect of the voluntary movement on the amplitude
      of the somatosensory evoked potentials (SEPs) recorded by an epidural electrode
      at level of the cervical spinal cord (CSC). METHODS: Fourteen patients underwent
      an epidural electrode implant at CSC level for pain relief. After the median
      nerve stimulation, SEPs were recorded from the epidural electrode and from 4
      surface electrodes (in frontal and parietal regions contralateral to the
      stimulated side, over the 6th cervical vertebra, and on the Erb's point). SEPs
      were recorded at rest and during a voluntary flexo-extension movement of the
      stimulated wrist. Beyond the low-frequency SEPs, also the high-frequency
      oscillations (HFOs) were analysed. RESULTS: The epidural electrode contacts
      recorded a triphasic potential (P1-N1-P2), whose negative peak showed the same
      latency as the cervical N13 response. The epidural potential amplitude was
      significantly decreased during the voluntary movement, as compared to the rest.
      Two main HFOs were identifiable: (1) the 1200 Hz HFO which was significantly
      lower in amplitude during movement than at rest, and (2) the 500 Hz HFO which was
      not modified by the voluntary movement. CONCLUSIONS: The low-frequency cervical
      SEP component is subtended by HFOs probably generated by: (1) postsynaptic
      potentials in the dorsal horn neurones (1200 Hz), and (2) presynaptic ascending
      somatosensory inputs (500 Hz). SIGNIFICANCE: Our findings show that the voluntary
      movement may affect the somatosensory input processing also at CSC level.

PMID- 18054282
TI  - Comment on: Hansen AM, Garde AH, Eller NH. Estimation of individual reference
      intervals in small sample sizes. Int. J. Hyg. Environ. Health 2007; 210: 471-478.

PMID- 18054283
TI  - Can excessive washing really be regarded as the major cause of atopic dermatitis?

PMID- 18054284
TI  - Innate immune recognition at the epithelial barrier drives adaptive immunity:
      APCs take the back seat.
AB  - Innate immune recognition of microbe-associated molecular patterns by multiple
      families of pattern-recognition molecules such as Toll-like receptors and Nod
      like receptors instructs the innate and adaptive immune system to protect the
      host from pathogens while also acting to establish a beneficial mutualism with
      commensal organisms. Although this task has been thought to be performed mainly
      by specialized antigen-presenting cells such as dendritic cells, recent
      observations point to the idea that innate immune recognition by stromal cells
      has important implications for the regulation of mucosal homeostasis as well as
      for the initiation of innate and adaptive immunity.

PMID- 18054285
TI  - Fungal stealth technology.
AB  - Medically important fungi range from commensal organisms that cause opportunistic
      infections to primary fungal pathogens that can cause disease in immunocompetent
      hosts. Host phagocyte-expressed pattern-recognition receptors represent one
      obstacle to infection, and the extent to which fungal cells can evade detection
      by host receptors helps shape their pathogenic potential. This review highlights
      recently defined mechanisms employed by successful fungal pathogens to conceal
      their immunostimulatory molecular signatures from leukocyte receptors or to
      disrupt host response signals. Continued improvements in our understanding of
      these fungal stealth mechanisms should provide new options for future
      therapeutics to expose these fungal pathogens and limit their virulence capacity.

PMID- 18054286
TI  - What's going on in LDL apheresis.

PMID- 18054287
TI  - Decrease of CD4(+)CD25(high)Foxp3(+) regulatory T cells and elevation of
      CD19(+)BAFF-R(+) B cells and soluble ICAM-1 in myasthenia gravis.
AB  - Myasthenia gravis (MG) is caused by T-cell-dependent autoantibodies against
      muscle acetylcholine receptors (AChR) at the neuromuscular junction. Here, we
      adopted ELISA and flow cytometry techniques to measure the levels of Th1, Th2,
      Th3 cytokines, inflammatory cytokine and chemokine sICAM-1 and to analyze the
      phenotypes of CD4(+) and CD8(+) regulatory cells as well as the expression of
      BAFF-R on CD19(+) B cells in peripheral blood from 75 MG patients and 50 healthy
      controls. There were no differences in the levels of IL-2, IL-4, IL-10, IL-13,
      IFN-gamma, TNF-alpha, TGF-beta and sCTLA-4 in both sera and culture supernatants
      between MG patients and healthy controls. The level of IL-12 was decreased in
      culture supernatants from MG patients, and the level of sICAM-1 was increased in
      both sera and culture supernatants from MG patients. Although the populations of
      CD8(+)CD28(-) and CD8(+)CD122(+) regulatory T cells were not different between MG
      patients and healthy controls, MG patients exhibited the decrease of
      CD4(+)CD25(high)Foxp3(+) regulatory T cells and the increase of CD19(+)BAFF-R(+)
      B cells, revealing that MG patients should display the dysfunction of T cell
      balance and the activation of B cell maturation.

PMID- 18054288
TI  - Ictal neuropsychological findings in focal nonconvulsive status epilepticus.
AB  - OBJECTIVE: This study was intended to describe the neuropsychological
      phenomenology of focal nonconvulsive status epilepticus (NCSE). METHODS: Ictal,
      postictal, and interictal neuropsychological testing (NPT) was performed on six
      patients who developed NCSE during video/electroencephalographic monitoring in
      the context of presurgical evaluation. RESULTS: Neuropsychological impairments
      were marked in four of six and discrete in two of six patients. The majority of
      patients had selective rather than global neuropsychological deficits. The most
      important deficits involved consciousness, speech, praxis, cognitive functions,
      and affect. Impairment of consciousness was characterized by reduced vigilance,
      reactivity, and orientation. Some patients exhibited combined deficits of several
      higher cognitive functions (apraxia, acalculia, alexia, and aphasia with or
      without additional memory disturbance). Several patients had relatively subtle
      expressive or receptive aphasia. More severe language deficits were associated
      with reduced vigilance. Speech deficits may have caused poor performance in other
      areas evaluated with NPT. CONCLUSION: NPT demonstrated that focal NCSE can be
      associated with pleomorphic but often discrete neuropsychological deficits.

PMID- 18054290
TI  - Dynamic expression of the zinc-finger transcription factor Trps1 during hair
      follicle morphogenesis and cycling.
AB  - Mutations in the gene encoding the zinc finger transcription factor TRPS1 result
      in tricho-rhino-phalangeal syndrome, characterized by craniofacial and skeletal
      abnormalities, and sparse scalp hair. In this study, Trps1 was identified by
      microarray hybridization analysis as having a complex pattern of spatiotemporal
      regulation in murine skin during morphogenesis. During early skin development,
      Trps1 expression decreased in the epidermis while simultaneously increasing in
      the dermis. Trps1 was specifically expressed in the nuclei of mesenchymal cells
      during hair follicle morphogenesis. An analysis of Trps1 expression during
      postnatal murine hair follicle cycling revealed that the protein localized to the
      nuclei of dermal papillae cells during telogen and anagen. Additionally, we found
      that Trps1 consistently localized to the nuclei of dermal papillae cells and the
      highly proliferative epithelial cells of mouse, rat and human hair follicles.

PMID- 18054289
TI  - Hierarchical models to evaluate translational research: Connecticut collaboration
      for fall prevention.
AB  - BACKGROUND AND OBJECTIVE: Evidence-based second stage translational studies are
      necessary and difficult to evaluate. A quasi-experimental design is used to
      compare the rate of fall-related health care utilization of two geographically
      disparate areas in Connecticut, a small state in the northeastern United States,
      to evaluate an intervention designed to reduce fall-related injuries among older
      persons. This evaluation examines the two years immediately prior to
      intervention. METHODS: The experimental units are postal (i.e., zip) code
      tabulation areas (ZCTAs) in which counts of fall-related health care utilization
      and demographic characteristics can be gathered from local and federal public
      health sources. We employ hierarchical modeling to determine whether there was a
      difference in fall-related health care utilization between the study arms prior
      to initiating the intervention. Geographic information systems are used to
      characterize neighboring ZCTAs and to graph model-adjusted rates of fall-related
      utilization. RESULTS: After adjustment for covariates and spatial variation, we
      observed no significant difference between rates or temporal trends of fall
      related health care utilization in the study arms over the two year pre
      intervention period. CONCLUSION: The study arms of the Connecticut Collaboration
      for Falls Prevention have equivalent rates and temporal trends of fall-related
      utilization over the two year pre-intervention period.

PMID- 18054291
TI  - The contribution of mitochondrial dysfunction to a gene-environment model of
      Guamanian ALS and PD.
AB  - Scientific investigations of amyotrophic lateral sclerosis (ALS) and parkinsonism
      dementia (PD) of Guam have implicated genetic and environmental risk factors in
      their etiology. Using brain tissue, we investigated mitochondrial dysfunction and
      report a higher frequency of somatic mutations in the light strand promoter (LSP)
      of the mitochondrial control region in Guam ALS and PD patients than in Guam
      controls, along with the presence of inherited mutations that may contribute to a
      novel gene-environment interaction risk model. Along with other risk factors,
      they demonstrate both the importance and significance of genetic and
      environmental contributions to Guam ALS and PD etiology.

PMID- 18054292
TI  - Determination of aldosterone in serum by liquid chromatography-tandem mass
      spectrometry.
AB  - Measurement of serum aldosterone is clinically important in the diagnosis of
      hypertension. While isotope dilution gas chromatography-mass spectrometry (ID-GC
      MS) provides reliable results, it requires derivatization and is lengthy and time
      consuming. Detection by liquid chromatography-mass spectrometry (LC-MS) is a
      potentially superior method. The analysis utilizes 0.5mL of serum. The samples
      were extracted with dichloromethane-ether. The extract was evaporated to dryness
      and aldosterone was analyzed by LC-MS/MS operating in the negative mode ESI after
      separation on a reversed-phase column. Aldosterone was also measured by RIA. The
      calibration curves for analysis of serum aldosterone exhibited consistent
      linearity and reproducibility in the range of 60-3000pmol/L. Interassay CVs were
      4.3-7.5% at aldosterone concentrations of 97-993pmol/L. The lower limit of
      quantitation (LOQ) was 30pmol/L (signal to noise ratio=10). The mean recovery of
      the analyte added to serum ranged from 95 to 102%. The regression equation by LC
      MS/MS (x) and RIA (y) method was: y=1.33x+185 (r=0.95; n=124). Sensitivity and
      specificity of the LC-MS/MS method for serum aldosterone offer advantages over GC
      MS by eliminating derivatization. The novel method is rapid, reliable and simple
      to perform with a routine LC-MS/MS spectrometer. The sensitivity is adequate for
      patient samples. Aldosterone concentrations reported by nonextraction RIA were
      consistently higher than those produced by LC-MS/MS.

PMID- 18054293
TI  - Phase diagrams of a CTAB/organic solvent/buffer system applied to extraction of
      enzymes by reverse micelles.
AB  - A partial pseudo-ternary phase diagram has been studied for the
      cethyltrimethylammonium bromide/isooctane:hexanol:butanol/potassium phosphate
      buffer system, where the two-phase diagram consisting of the reverse micelle
      phase (L2) in equilibrium with the solvent is indicated. Based on these diagrams
      two-phase systems of reverse micelles were prepared with different compositions
      of the compounds and used for extraction and recovery of two enzymes, and the
      percentage of enzyme recovery yield monitored. The enzymes glucose-6-phosphate
      dehydrogenase (G6PD) and xylose redutase (XR) obtained from Candida
      guilliermondii yeast were used in the extraction procedures. The recovery yield
      data indicate that micelles having different composition give selective
      extraction of enzymes. The method can thus be used to optimize enzyme extraction
      processes.

PMID- 18054294
TI  - Preparative chromatographic purification of diastereomers of silybin and their
      quantification in human plasma by liquid chromatography-tandem mass spectrometry.
AB  - A novel preparative HPLC method separating silybin has been developed to meet the
      need for both silybin A and silybin B standard. After the preparation of silybin
      A and silybin B standard, a simple, sensitive, selective and reproducible liquid
      chromatography-tandem mass spectrometry (LC-MS-MS) method with negative
      electrospray ionization (ESI) was developed for the quantification of silybin A
      and silybin B in human plasma. Following rapid sample preparation, silybin A,
      silybin B and naringin (internal standard, ISTD) were separated on a Zorbax
      Eclipse XDB-C18 column, using methanol-water containing 0.1% formic acid (48:52,
      v/v) as the mobile phase. The mass spectrometer was operated in selected reaction
      monitoring (SRM) mode using the transition m/z 481.1-->300.9 for both silybin A
      and silybin B and m/z 579.2-->271.1 for naringin, respectively. Linear
      calibration curves were obtained in the concentration range of 2-5000ng/ml with a
      lower limit of quantitation (LLOQ) of 2ng/ml for both silybin A and silybin B,
      respectively. The intra- and inter-day precision values were below 7.5% and
      accuracy was within +/-4.9% at all three quality control (QC) levels, for both
      silybin A and silybin B, respectively. This method was successfully applied to
      the stereospecific analysis of silybin in plasma samples from a pharmacokinetic
      study of silybin A and silybin B in 22 healthy male Chinese volunteers after a
      single oral dose of silybin-phosphatidylcholine complex (equivalent to 280mg
      silybin, including 133mg silybin A and 147mg silybin B).

PMID- 18054295
TI  - Height, health, and income in the US, 1984--2005.
AB  - Height has been associated with better physical health when outcomes such as
      diabetes, heart disease, and obesity are considered, yet stature is rarely used
      in predicting comorbidities or as a proxy for physical health when analyzing
      outcomes such as income. Since height is a more exogenous measure than variables
      likely to be affected by lifestyle changes, such as obesity, observing labor
      market outcomes based on height may be revealing. In addition, gender and racial
      differences must be taken into account when analyzing the effects of height on
      physical health and labor market outcomes. This study utilizes the 1984--2005
      samples of the Behavioral Risk Factor Surveillance System in estimating trends in
      height over time by gender and race, and in analyzing the relationship between
      height and physical health and labor market outcomes in the United States. Trends
      show that height has not changed substantially at a time when physical health, as
      indicated by the incidence of obesity, Type II diabetes, and cholesterol, has
      deteriorated, and earnings disparities across racial gaps persist. Results at
      mean values for males indicate that being 10cm taller is associated with a 14-47%
      increase in obesity, an 8-13% reduction in cholesterol prevalence, and a $1874
      2306 income premium. For females, results indicate that being 10cm taller is
      associated with an 8-18% reduction in cholesterol, a 14% reduction in diabetes
      for white females, and an $891-2243 earnings premium.

PMID- 18054296
TI  - A hypothetical road map to reduce acid related diseases costs management.

PMID- 18054298
TI  - Functionally graded Co-Cr-Mo coating on Ti-6Al-4V alloy structures.
AB  - Functionally graded, hard and wear-resistant Co-Cr-Mo alloy was coated on Ti-6Al
      4V alloy with a metallurgically sound interface using Laser Engineering Net
      Shaping (LENS). The addition of the Co-Cr-Mo alloy onto the surface of Ti-6Al-4V
      alloy significantly increased the surface hardness without any intermetallic
      phases in the transition region. A 100% Co-Cr-Mo transition from Ti-6Al-4V was
      difficult to produce due to cracking. However, using optimized LENS processing
      parameters, crack-free coatings containing up to 86% Co-Cr-Mo were deposited on
      Ti-6Al-4V alloy with excellent reproducibility. Human osteoblast cells were
      cultured to test in vitro biocompatibility of the coatings. Based on in vitro
      biocompatibility, increasing the Co-Cr-Mo concentration in the coating reduced
      the live cell numbers after 14 days of culture on the coating compared with base
      Ti-6Al-4V alloy. However, coated samples always showed better bone cell
      proliferation than 100% Co-Cr-Mo alloy. Producing near net shape components with
      graded compositions using LENS could potentially be a viable route for
      manufacturing unitized structures for metal-on-metal prosthetic devices to
      minimize the wear-induced osteolysis and aseptic loosening that are significant
      problems in current implant design.

PMID- 18054297
TI  - Mechanical and biological properties of hydroxyapatite/tricalcium phosphate
      scaffolds coated with poly(lactic-co-glycolic acid).
AB  - Regeneration of bone, cartilage and osteochondral tissues by tissue engineering
      has attracted intense attention due to its potential advantages over the
      traditional replacement of tissues with synthetic implants. Nevertheless, there
      is still a dearth of ideal or suitable scaffolds based on porous biomaterials,
      and the present study was undertaken to develop and evaluate a useful porous
      composite scaffold system. Here, hydroxyapatite (HA)/tricalcium phosphate (TCP)
      scaffolds (average pore size: 500 microm; porosity: 87%) were prepared by a
      polyurethane foam replica method, followed by modification with infiltration and
      coating of poly(lactic-co-glycolic acid) (PLGA). The thermal shock resistance of
      the composite scaffolds was evaluated by measuring the compressive strength
      before and after quenching or freezing treatment. The porous structure (in terms
      of pore size, porosity and pore interconnectivity) of the composite scaffolds was
      examined. The penetration of the bone marrow stromal stem cells into the
      scaffolds and the attachment of the cells onto the scaffolds were also
      investigated. It was shown that the PLGA incorporation in the HA/TCP scaffolds
      significantly increased the compressive strength up to 660 kPa and the residual
      compressive strength after the freezing treatment decreased to 160 kPa, which
      was, however, sufficient for the scaffolds to withstand subsequent cell culture
      procedures and a freeze-drying process. On the other hand, the PLGA coating on
      the strut surfaces of the scaffolds was rather thin (<5 microm) and apparently
      porous, maintaining the high open porosity of the HA/TCP scaffolds, resulting in
      desirable migration and attachment of the bone marrow stromal stem cells,
      although a thicker PLGA coating would have imparted a higher compressive strength
      of the PLGA-coated porous HA/TCP composite scaffolds.

PMID- 18054299
TI  - Osteoblast-like cell proliferation on tape-cast and sintered tricalcium phosphate
      sheets.
AB  - The influence of sintering temperature on the in vitro proliferation of
      osteoblast-like cells to sintered tricalcium phosphate (TCP) sheets prepared by
      tape-casting was investigated. Green sheets of tape-cast beta-TCP were sintered
      for 2h in a furnace at atmospheric pressure at five different sintering
      temperatures: 900, 1000, 1100, 1150 and 1200 degrees C. The number of osteoblast
      like (MC3T3-E1) cells deposited onto TCP sheets was counted after cell
      cultivation for 1week and was found to have increased with increasing sintering
      temperature. The TCP sheets sintered at 900 degrees C exhibited a significantly
      lower cell number than TCP sheets sintered at 1000, 1100, 1150 and 1200 degrees
      C. In the attenuated total reflection infrared spectra, the peaks around 900
      1150cm(-1), corresponding to the P-O vibration mode of the phosphate group,
      gradually decreased and shifted to lower wavenumbers with increasing sintering
      temperature. Meanwhile, the zeta potential of TCP sintered at 900 degrees C
      showed a highly negative charge when compared with the other groups. This would
      suggest that the higher solubility of the TCP sheets sintered at 900 degrees C
      exerted the higher negative charge obtained from zeta potential measurement.
      Within the limitations of this study, it was indicated that osteoblast-like cell
      proliferation increased with increasing sintering temperature. The biological
      stability of the sintered TCP sheet surface was considered to have affected cell
      proliferation.

PMID- 18054300
TI  - Microvascular ear reconstruction using a free radial forearm flap after dog bite.
AB  - A 68-year old woman suffered from a subtotal amputation of the left ear due to a
      dog bite. The recovered ear was implanted and reconstructed using a radial
      forearm flap. In our opinion, the forearm is an excellent choice for implantation
      of recovered ear cartilage as preparation for one-stage reconstruction.

PMID- 18054301
TI  - Results of the early use of tissue expansion for giant congenital melanocytic
      naevi on the scalp and face.
AB  - SUMMARY INTRODUCTION: Giant congenital melanocytic naevi (GCMN) are uncommon,
      have a significant morbidity and require extensive treatment. This paper presents
      results after complete excision of GCMN on the scalp, forehead or periorbita
      after early tissue expansion. Based on 15 years of experience, we want to show
      that performing tissue expansion at a young age is advisable. PATIENTS AND
      METHODS: We included 17 consecutive patients in whom 38 tissue expanders were
      used. Early and late complications were noted. Patients were seen for a clinical
      follow up in which scars and re-pigmentation were evaluated with a validated scar
      scale (POSAS). RESULTS: All GCMN could be excised completely with early tissue
      expansion. The age at treatment ranged from 4 months to 2 years of age. With a
      mean follow-up period of 8.7 years, mild re-pigmentation was seen in only three
      patients and none of the patients developed a malignant melanoma. Complication
      rates are comparable with the literature. CONCLUSION: Tissue expansion is a good
      method for removing GCMN located at the scalp or face with good cosmetic and
      oncological results. Performing tissue expansion at a young age is advisable.

PMID- 18054302
TI  - Improving postoperative analgesia for transverse rectus abdominis myocutaneous
      flap breast reconstruction; the use of a local anaesthetic infusion catheter.
AB  - SUMMARY: Postoperative pain relief can be delivered either directly to the
      operative site, or systemically. When effective analgesia can be provided
      locally, the side effects of systemic analgesia can be avoided, reducing the
      morbidity of the procedure. We examined the effects of delivering local
      anaesthetic to the rectus sheath via a multilumen infusion catheter following
      transverse rectus abdominis myocutaneous (TRAM) flap surgery, and compared the
      outcomes with patients managed using patient-controlled analgesia (PCA). Forty
      six TRAM flap patients received either PCA, local anaesthetic infusion and PCA,
      or local anaesthetic infusion and supplemental opioid as needed, and the
      analgesic requirements and morbidity associated with the use of these analgesic
      medications were recorded. The use of local anaesthetic infusion significantly
      reduced both total opioid use (71.7% reduction) and nausea, as reflected in the
      reduction of antiemetic required (51.5% reduction). Fourteen patients were also
      successful managed with just the infusion catheter and supplementary analgesia,
      avoiding completely the use of PCA. A 1.5-day reduction in length of
      hospitalisation was also found. Local anaesthetic infusion delivery to the rectus
      sheath significantly reduces narcotic requirements, may eliminate the need for
      PCA, and has an associated significant decrease in the postoperative nausea and
      vomiting commonly seen in TRAM breast reconstructions.

PMID- 18054303
TI  - Autologous breast augmentation with the lateral intercostal artery perforator
      flap in massive weight loss patients.
AB  - The body contour deformities that develop in morbidly obese patients following
      bariatric surgery often involve the breasts. Mastopexy is virtually always
      required in the female massive weight loss patient, and breast augmentation is
      often an important adjunct to breast-lifting procedures. The lateral intercostal
      artery perforator (LICAP) pedicled flap provides ample material for autogenous
      breast augmentation in such patients. Between June 2001 and June 2005, bilateral
      LICAP flaps were used as a method of autologous breast augmentation in six
      patients after massive weight loss. Of the 12 pedicled LICAP flaps raised, the
      average flap dimension was 23.6x10.6 cm. Mean flap harvesting time was 60 min
      (range 45-75 min) for a single flap. All but two flaps were based on one
      perforator. All donor sites were closed primarily. Complete flap survival was
      achieved in all cases. A minor wound dehiscence occurred in two cases both of
      which healed secondarily. Patient satisfaction with both the appearance of their
      breasts and lateral axillary-thoracic region was high. The improved contour of
      the lateral axillary region was frequently noted as a significant benefit. In
      massive weight loss patients, harvesting the lateral skin-fat excess based on the
      LICAP provides supple tissue for breast augmentation, while simultaneously
      improving the contour of this area frequently affected by skin excess.
      Additionally, harvesting these flaps without sacrifice of the underlying muscle
      eases postoperative recovery and reduces donor site morbidity.

PMID- 18054304
TI  - Gigantomastia--a classification and review of the literature.
AB  - INTRODUCTION: Gigantomastia is a rare, psychologically and physically disabling
      condition characterised by excessive breast growth. To date, there is no
      universal classification or accepted definition for this condition. Many authors
      cite gigantomastia as breast enlargement that requires reduction of over 1500 g
      per breast. However, there is discordance in the literature with the weight of
      reduction ranging from 0.8 to 2 kg, or even a D cup bra size. Practically this is
      a postoperative definition which is of little use to the clinician in terms of
      patient management or prognosis. METHOD: We conducted a literature review and
      meta analysis of all published cases of gigantomastia. We combined this with
      seven cases managed at Selly Oak Hospital, Birmingham, to give us a series of 115
      patients. In order to devise a universally accepted definition of gigantomastia,
      a survey of 150 plastic surgery consultants within Europe was conducted.
      Participants were e-mailed a questionnaire, requesting their definition of
      gigantomastia with an appropriate excision weight. They were also asked to
      comment on any preoperative measurements taken to establish this predicted
      weight. CONCLUSION: We propose a classification of gigantomastia based on the
      cause, management and prognosis of the disease.

PMID- 18054305
TI  - Influence of controlled hypotension versus normotension on amount of blood loss
      during breast reduction.
AB  - SUMMARY: Controlled hypotension employed during surgical procedures results in a
      beneficial reduction in blood loss during the operation. Breast reduction is a
      common cosmetic surgical procedure. Yet, in the Netherlands, controlled
      hypotension is not standard during breast reduction procedures, and in fact is
      only occasionally employed. Our research aimed to establish a set of guidelines
      which would outline the application of controlled hypotension during breast
      reduction surgery. The set up of the study was prospective. The patients were
      randomised into two groups. In the test group, controlled hypotension with an
      average of 30% reduction in systolic tension was established during the first
      operative phase. For the control group, normotension was maintained during the
      entire procedure. The blood loss in the test group (n=23; mean 318 cc) was
      reduced by 54.1% compared to control (n=28; mean 598 cc), and this difference was
      significant. A significant positive correlation was also found between blood loss
      and total incision time. An overall complication rate of 5.1% was observed;
      however, there was no significant difference between the two groups. A trend in
      favour of hypotension does suggest it may also help reduce postoperative
      complications. Our data indicate that a reduction in blood loss of more than 50%
      can be achieved by employing controlled hypotension in the first operative phase
      of breast reduction. A reduction in systolic pressure of 20-25% with the use of
      nitroprusside is sufficient to achieve this reduced blood loss.

PMID- 18054306
TI  - The Amplatz canine duct occluder: a novel device for patent ductus arteriosus
      occlusion.
AB  - The Amplatz canine duct occluder (ACDO) is a nitinol mesh device with a short
      waist that separates a flat distal disc from a cupped proximal disc. The device
      is designed to conform to the morphology of the canine patent ductus arteriosus
      (PDA). PDA dimensions are determined by angiography, and a guiding catheter is
      advanced into the main pulmonary artery via the aorta and PDA. An ACDO with a
      waist diameter approximately twice the angiographic minimal ductal diameter (MDD)
      is advanced via the catheter using an attached delivery cable until the flat
      distal disc deploys within the main pulmonary artery. The partially deployed
      ACDO, guiding catheter, and delivery cable are retracted until the distal disc
      engages the pulmonic ostium of the PDA. With the delivery cable stabilized, the
      catheter is retracted to deploy the waist across the pulmonic ostium and cupped
      proximal disc within the ductal ampulla. Tension on the delivery cable is
      released, and correct ACDO positioning and stability are confirmed by observing
      that the device assumes its native shape, back-and-forth maneuvering of the
      delivery cable, and a small contrast injection made through the guiding catheter.
      The delivery cable is detached and removed with the guiding catheter. To assess
      for any residual ductal flow, an angiogram is performed at the conclusion of the
      procedure, followed by Doppler echocardiography at 1 day and 3 months post
      procedure. PDA occlusion in dogs with the ACDO is straightforward and extremely
      effective across a wide range of body weights, somatotypes, MDDs, and ductal
      morphologies.

PMID- 18054307
TI  - DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the
      Netherlands.
AB  - Joubert syndrome (JBS) is a clinically variable and genetically heterogeneous
      developmental brain disorder with autosomal recessive inheritance. Five genes,
      AHI1, NPHP1, CEP290, MKS3, and RPGRIP1L, and two additional loci on chromosome 9
      and 11 have been identified so far. The relative contributions of AHI1 mutations
      and NPHP1 deletions have not yet been determined in a population-based JBS
      patient cohort. We therefore undertook a nationwide survey of JBS in the
      Netherlands and performed DNA analysis of the AHI1 and NPHP1 genes, as well as a
      new candidate gene CYCLIN D1. We obtained clinical data and DNA samples of 25
      Dutch JBS patients. DNA analysis of AHI1 revealed pathogenic homozygous or
      compound heterozygous AHI1 mutations in four patients (16%). Based on the birth
      prevalence of about 1 in 100,000 for JBS in the Netherlands, we estimated a
      carrier frequency of AHI1 mutations of approximately 1 in 400. In another two
      patients, the AHI1 mutation Arg830Trp was identified (homozygously and
      heterozygously), a possible low penetrance allele. No deletions of NPHP1 or
      CYCLIN D1 mutations were detected in these 25 patients. In the four patients with
      AHI1 mutations, retinal disease (Leber congenital amaurosis or retinal dystrophy)
      was present in two, whereas none had renal disease. Pooling our data and data
      from the literature, retinal disease seems to occur in 75% of AHI1-associated JBS
      patients. Renal disease is present in 10% at most. We conclude that AHI1
      mutations are an important cause of JBS in Dutch patients, and should always be
      looked for in patients suspected of JBS, especially when retinal dystrophy is
      present. Patients with AHI1 mutations should be regularly checked for retinal and
      renal disease up until adolescence.

PMID- 18054308
TI  - Impact of geometry and viewing angle on classification accuracy of 2D based
      analysis of dysmorphic faces.
AB  - Digital image analysis of faces has been demonstrated to be effective in a small
      number of syndromes. In this paper we investigate several aspects that help
      bringing these methods closer to clinical application. First, we investigate the
      impact of increasing the number of syndromes from 10 to 14 as compared to an
      earlier study. Second, we include a side-view pose into the analysis and third,
      we scrutinize the effect of geometry information. Picture analysis uses a Gabor
      wavelet transform, standardization of landmark coordinates and subsequent
      statistical analysis. We can demonstrate that classification accuracy drops from
      76% for 10 syndromes to 70% for 14 syndromes for frontal images. Including side
      views achieves an accuracy of 76% again. Geometry performs excellently with 85%
      for combined poses. Combination of wavelets and geometry for both poses increases
      accuracy to 93%. In conclusion, a larger number of syndromes can be handled
      effectively by means of image analysis.

PMID- 18054310
TI  - Imaging obesity: fMRI, food reward, and feeding.
AB  - Animal studies have revealed brain regions that control homeostatic feeding, but
      the rampant overeating contributing to the obesity epidemic suggests the
      participation of "nonhomeostatic" control centers. Recent papers by Batterham et
      al. (2007) and Farooqi et al. (2007) link peptide YY(3-36) and leptin to the
      activation of nonhomeostatic brain regions.

PMID- 18054311
TI  - FoxO3 controls dangerous proteolytic liaisons.
AB  - FoxO3 regulates the transcription of critical components of the ubiquitin
      proteasome system in muscle wasting. Two reports (Mammucari et al., 2007; Zhao et
      al., 2007) now implicate FoxO3 in the transcription of autophagy-related genes
      and provide the first direct evidence for a coordinated role of autophagy in
      muscle atrophy.

PMID- 18054312
TI  - Mitochondria and aging: dilution is the solution.
AB  - Metabolic component depletion in model systems results in life-span extension,
      which has been difficult to reconcile with human metabolic pathologies. Recently,
      Rea et al. (2007) have shown that mitochondrial electron transport chain RNAi
      phenotypes in the worm C. elegans are dose dependent, providing an alternative
      view of mitochondrial function in longevity and metabolic diseases.

PMID- 18054313
TI  - Enhanced leptin-stimulated Pi3k activation in the CNS promotes white adipose
      tissue transdifferentiation.
AB  - The contribution of different leptin-induced signaling pathways in control of
      energy homeostasis is only partly understood. Here we show that selective Pten
      ablation in leptin-sensitive neurons (Pten(DeltaObRb)) results in enhanced Pi3k
      activation in these cells and reduces adiposity by increasing energy expenditure.
      White adipose tissue (WAT) of Pten(DeltaObRb) mice shows characteristics of brown
      adipose tissue (BAT), reflected by increased mitochondrial content and Ucp1
      expression resulting from enhanced leptin-stimulated sympathetic nerve activity
      (SNA) in WAT. In contrast, leptin-deficient ob/ob-Pten(DeltaObRb) mice exhibit
      unaltered body weight and WAT morphology compared to ob/ob mice, pointing to a
      pivotal role of endogenous leptin in control of WAT transdifferentiation.
      Leanness of Pten(DeltaObRb) mice is accompanied by enhanced sensitivity to
      insulin in skeletal muscle. These data provide direct genetic evidence that
      leptin-stimulated Pi3k signaling in the CNS regulates energy expenditure via
      activation of SNA to perigonadal WAT leading to BAT-like differentiation of WAT.

PMID- 18054314
TI  - Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery
      disease.
AB  - The Akt signaling pathway controls several cellular functions in the
      cardiovascular system; however, its role in atherogenesis is unknown. Here, we
      show that the genetic ablation of Akt1 on an apolipoprotein E knockout background
      (ApoE(-/-)Akt1(-/-)) increases aortic lesion expansion and promotes coronary
      atherosclerosis. Mechanistically, lesion formation is due to the enhanced
      expression of proinflammatory genes and endothelial cell and macrophage
      apoptosis. Bone marrow transfer experiments showing that macrophages from ApoE(-/
      )Akt1(-/-) donors were not sufficient to worsen atherogenesis when transferred to
      ApoE(-/-) recipients suggest that lesion expansion in the ApoE(-/-)Akt1(-/-)
      strain might be of vascular origin. In the vessel wall, the loss of Akt1
      increases inflammatory mediators and reduces eNOS phosphorylation, suggesting
      that Akt1 exerts vascular protection against atherogenesis. The presence of
      coronary lesions in ApoE(-/-)Akt1(-/-) mice provides a new model for studying the
      mechanisms of acute coronary syndrome in humans.

PMID- 18054315
TI  - FoxO3 controls autophagy in skeletal muscle in vivo.
AB  - Autophagy allows cell survival during starvation through the bulk degradation of
      proteins and organelles by lysosomal enzymes. However, the mechanisms responsible
      for the induction and regulation of the autophagy program are poorly understood.
      Here we show that the FoxO3 transcription factor, which plays a critical role in
      muscle atrophy, is necessary and sufficient for the induction of autophagy in
      skeletal muscle in vivo. Akt/PKB activation blocks FoxO3 activation and
      autophagy, and this effect is not prevented by rapamycin. FoxO3 controls the
      transcription of autophagy-related genes, including LC3 and Bnip3, and Bnip3
      appears to mediate the effect of FoxO3 on autophagy. This effect is not prevented
      by proteasome inhibitors. Thus, FoxO3 controls the two major systems of protein
      breakdown in skeletal muscle, the ubiquitin-proteasomal and autophagic/lysosomal
      pathways, independently. These findings point to FoxO3 and Bnip3 as potential
      therapeutic targets in muscle wasting disorders and other degenerative and
      neoplastic diseases in which autophagy is involved.

PMID- 18054316
TI  - FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and
      proteasomal pathways in atrophying muscle cells.
AB  - Muscle atrophy occurs in many pathological states and results primarily from
      accelerated protein degradation and activation of the ubiquitin-proteasome
      pathway. However, the importance of lysosomes in muscle atrophy has received
      little attention. Activation of FoxO transcription factors is essential for the
      atrophy induced by denervation or fasting, and activated FoxO3 by itself causes
      marked atrophy of muscles and myotubes. Here, we report that FoxO3 does so by
      stimulating overall protein degradation and coordinately activating both
      lysosomal and proteasomal pathways. Surprisingly, in C2C12 myotubes, most of this
      increased proteolysis is mediated by lysosomes. Activated FoxO3 stimulates
      lysosomal proteolysis in muscle (and other cell types) by activating autophagy.
      FoxO3 also induces the expression of many autophagy-related genes, which are
      induced similarly in mouse muscles atrophying due to denervation or fasting.
      These studies indicate that decreased IGF-1-PI3K-Akt signaling activates
      autophagy not only through mTOR but also more slowly by a transcription-dependent
      mechanism involving FoxO3.

PMID- 18054317
TI  - Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate
      induced adiposity and hepatic steatosis.
AB  - Stearoyl-CoA desaturase-1 (SCD1), a critical regulator of energy metabolism,
      catalyzes the synthesis of monounsaturated fats. To understand the tissue
      specific role of SCD1 in energy homeostasis, we used Cre-lox technology to
      generate mice with a liver-specific knockout of Scd1 (LKO). LKO mice were
      protected from high-carbohydrate, but not high-fat (HF), diet-induced adiposity
      and hepatic steatosis. Additionally, on a high-sucrose, very low-fat (HSVLF)
      diet, lipogenesis and levels of nuclear SREBP-1 and ChREBP were significantly
      decreased in the livers of LKO relative to Scd1(lox/lox) (Lox) mice. HSVLF
      feeding in LKO mice caused hypoglycemia and hepatic carbohydrate reduction due to
      an impairment of gluconeogenesis. Oleate, but not stearate, supplementation
      normalized adiposity, gluconeogenesis, triglyceride secretion, and hepatic
      lipogenesis of LKO mice. These results indicate that hepatic SCD1 expression (and
      thus, oleate) is required for carbohydrate-induced adiposity, but SCD1 inhibition
      in extrahepatic tissues is required to protect mice from HF-induced obesity and
      insulin resistance.

PMID- 18054318
TI  - Respiratory uncoupling in skeletal muscle delays death and diminishes age-related
      disease.
AB  - Age-related disease, not aging per se, causes most morbidity in older humans.
      Here we report that skeletal muscle respiratory uncoupling due to UCP1 expression
      diminishes age-related disease in three mouse models. In a longevity study,
      median survival was increased in UCP mice (animals with skeletal muscle-specific
      UCP1 expression), and lymphoma was detected less frequently in UCP female mice.
      In apoE null mice, a vascular disease model, diet-induced atherosclerosis was
      decreased in UCP animals. In agouti yellow mice, a genetic obesity model,
      diabetes and hypertension were reversed by induction of UCP1 in skeletal muscle.
      Uncoupled mice had decreased adiposity, increased temperature and metabolic rate,
      elevated muscle SIRT and AMP kinase, and serum characterized by increased
      adiponectin and decreased IGF-1 and fibrinogen. Accelerating metabolism in
      skeletal muscle does not appear to impact aging but may delay age-related
      disease.

PMID- 18054320
TI  - Diabetes alters LDL receptor and PCSK9 expression in rat liver.
AB  - Since the hepatic LDL receptor is regarded as a major determinant of plasma LDL
      levels, the effect of diabetes on the expression of this receptor was examined in
      rat liver. Inducing diabetes with streptozotocin caused a significant reduction
      in hepatic LDL receptor mRNA levels in concert with an increase in serum
      cholesterol levels. However, LDL receptor protein levels were unaffected by the
      diabetic state. Further investigation revealed that protein levels of PCSK9,
      which has been shown to enhance the degradation of the LDL receptor protein, were
      significantly decreased in the diabetic rats explaining the lack of reduction in
      LDL receptor protein levels. These observations indicate that the rate of LDL
      receptor cycling (function) in diabetic rats is decreased resulting in higher
      serum LDL levels.

PMID- 18054319
TI  - Increased energy expenditure, dietary fat wasting, and resistance to diet-induced
      obesity in mice lacking renin.
AB  - An overactive renin-angiotensin system is associated with obesity and the
      metabolic syndrome. However, the mechanisms behind it are unclear. Cleaving
      angiotensinogen to angiotensin I by renin is a rate-limiting step of angiotensin
      II production, but renin is suggested to have angiotensin-independent effects. We
      generated mice lacking renin (Ren1c) using embryonic stem cells from C57BL/6
      mice, a strain prone to diet-induced obesity. Ren1c(-/-) mice are lean, insulin
      sensitive, and resistant to diet-induced obesity without changes in food intake
      and physical activity. The lean phenotype is likely due to a higher metabolic
      rate and gastrointestinal loss of dietary fat. Most of the metabolic changes in
      Ren1c(-/-) mice were reversed by angiotensin II administration. These results
      support a role for angiotensin II in the pathogenesis of diet-induced obesity and
      insulin resistance.

PMID- 18054321
TI  - Mitochondrial biogenesis in fast skeletal muscle of CK deficient mice.
AB  - Creatine kinase (CK) is a phosphotransfer kinase that catalyzes the reversible
      transfer of a phosphate moiety between ADP and creatine and that is highly
      expressed in skeletal muscle. In fast glycolytic skeletal muscle, deletion of the
      cytosolic M isoform of CK in mice (M-CK-/-) leads to a massive increase in the
      oxidative capacity and of mitochondrial volume. This study was aimed at
      investigating the transcriptional pathways leading to mitochondrial biogenesis in
      response to CK deficiency. Wild type and M-CK-/- mice of eleven months of age
      were used for this study. Gastrocnemius muscles of M-CK-/- mice exhibited a
      dramatic increase in citrate synthase (+120%) and cytochrome oxidase (COX, +250%)
      activity, and in mitochondrial DNA (+60%), showing a clear activation of
      mitochondrial biogenesis. Similarly, mRNA expression of the COXI (mitochondria
      encoded) and COXIV (nuclear-encoded) subunits were increased by +103 and +94%
      respectively. This was accompanied by an increase in the expression of the
      nuclear respiratory factor (NRF2alpha) and the mitochondrial transcription factor
      (mtTFA). Expression of the co-activator PGC-1alpha, a master gene in
      mitochondrial biogenesis was not significantly increased while that of PGC-1beta
      and PRC, two members of the same family, was moderately increased (+45% and +55%
      respectively). While the expression of the modulatory calcineurin-interacting
      protein 1 (MCIP1) was dramatically decreased (-68%) suggesting inactivation of
      the calcineurin pathway, the metabolic sensor AMPK was activated (+86%) in M-CK-/
      mice. These results evidence that mitochondrial biogenesis in response to a
      metabolic challenge exhibits a unique pattern of regulation, involving activation
      of the AMPK pathway.

PMID- 18054322
TI  - Modified glutamine catabolism in macrophages of Ucp2 knock-out mice.
AB  - Uncoupling protein 2 (UCP2) belongs to a family of transporters of the
      mitochondrial inner membrane and is reported to uncouple respiration from ATP
      synthesis. Our observation that the amino acid glutamine specifically induces
      UCP2 protein expression prompted us to investigate metabolic consequences of a
      UCP2 knockdown (Ucp2-KO) when glutamine is offered as a substrate. We found that
      Ucp2-KO macrophages incubated in the presence of glutamine exhibit a lower
      ammonium release, a decreased respiratory rate, and an intracellular accumulation
      of aspartate. Therefore, we conclude that UCP2 expression is required for
      efficient oxidation of glutamine in macrophages. This role of UCP2 in glutamine
      metabolism appears independent from the uncoupling activity of UCP2.

PMID- 18054323
TI  - MITO-Porter: A liposome-based carrier system for delivery of macromolecules into
      mitochondria via membrane fusion.
AB  - Mitochondria are the principal producers of energy in higher cells. Mitochondrial
      dysfunction is implicated in a variety of human diseases, including cancer and
      neurodegenerative disorders. Effective medical therapies for such diseases will
      ultimately require targeted delivery of therapeutic proteins or nucleic acids to
      the mitochondria, which will be achieved through innovations in the
      nanotechnology of intracellular trafficking. Here we describe a liposome-based
      carrier that delivers its macromolecular cargo to the mitochondrial interior via
      membrane fusion. These liposome particles, which we call MITO-Porters, carry
      octaarginine surface modifications to stimulate their entry into cells as intact
      vesicles (via macropinocytosis). We identified lipid compositions for the MITO
      Porter which promote both its fusion with the mitochondrial membrane and the
      release of its cargo to the intra-mitochondrial compartment in living cells.
      Thus, the MITO-Porter holds promise as an efficacious system for the delivery of
      both large and small therapeutic molecules into mitochondria.

PMID- 18054324
TI  - Spectroscopic and ITC study of the conformational change upon Ca2+-binding in TnC
      C-lobe and TnI peptide complex from Akazara scallop striated muscle.
AB  - Akazara scallop (Chlamys nipponensis akazara) troponin C (TnC) of striated
      adductor muscle binds only one Ca(2+) ion at the C-terminal EF-hand motif (Site
      IV), but it works as the Ca(2+)-dependent regulator in adductor muscle
      contraction. In addition, the scallop troponin (Tn) has been thought to regulate
      muscle contraction via activating mechanisms that involve the region spanning
      from the TnC C-lobe (C-lobe) binding site to the inhibitory region of the TnI,
      and no alternative binding of the TnI C-terminal region to TnC because of no
      similarity between second TnC-binding regions of vertebrate and the scallop TnIs.
      To clarify the Ca(2+)-regulatory mechanism of muscle contraction by scallop Tn,
      we have analyzed the Ca(2+)-binding properties of the complex of TnC C-lobe and
      TnI peptide, and their interaction using isothermal titration microcalorimetry,
      nuclear magnetic resonance, circular dichroism, and gel filtration
      chromatography. The results showed that single Ca(2+)-binding to the Site IV
      leads to a structural transition not only in Site IV but also Site III through
      the structural network in the C-lobe of scallop TnC. We therefore assumed that
      the effect of Ca(2+)-binding must lead to a change in the interaction mode
      between the C-lobe of TnC and the TnI peptide. The change should be the first
      event of the transmission of Ca(2+) signal to TnI in Tn ternary complex.

PMID- 18054325
TI  - An integrase of endogenous retrovirus is involved in maternal mitochondrial DNA
      inheritance of the mouse.
AB  - The mechanism of maternal mitochondrial DNA (mtDNA) inheritance in animals can be
      said to be the selective elimination of sperm mtDNA via the elimination factor of
      the egg and a sperm mitochondria-specific factor. In 2005, we clarified that t
      tpis (Spag1 isoform 1) is a mitochondria-specific translocator and the sperm
      factor, and furthermore estimated that the elimination factors of the egg are the
      divalent cation-dependent endonuclease and s-tpis (Spag1 isoform 2 and isoform 3)
      as the elimination system-specific chaperone [K. Hayashida, K. Omagari, J.
      Masuda, H. Hazama, Y. Kadokawa, K. Ohba, S. Kohno, The sperm mitochondria
      specific translocator has a key role in maternal mitochondrial inheritance, Cell
      Biol. Int. 29 (2005) 472-481]. This time, using a recombinant Spag1 isoform 1
      protein, a pull-down assay of ovary cytosol was performed and the elimination
      factors searched for. Surprisingly, an endogenous retroviral integrase fragment
      (Eri15) was identified using mass spectrometry of the electrophoresis band of the
      pull-down protein. Eri15 was detected as a complex of approximately 500kDa with
      Spag1 isoform 2 or isoform 3 in native PAGE of the ovary cytosol. This strongly
      suggested that Eri15 is selectively transported into the sperm mitochondria
      matrix by Spag1 isoform 2 and 3 via Spag1 isoform 1 and that sperm mtDNA is
      destroyed, thus causing the establishment of maternal mtDNA inheritance.

PMID- 18054326
TI  - Mitochondrial calpain 10 activity and expression in the kidney of multiple
      species.
AB  - Calpains, Ca(2+)-activated cysteine proteases, have been implicated in the
      progression of multiple disease states. We recently identified calpain 10 as a
      mitochondrial calpain that is involved in Ca(2+)-induced mitochondrial
      dysfunction. The goals of this study were to characterize the expression and
      activity of renal mitochondrial calpain 10 in rabbit, mouse, and rat. Using shRNA
      technology and immunoblot analysis three previously postulated splice variants of
      calpain 10 were identified (50, 56, and 75kDa). SLLVY-AMC zymography and
      immunoblot analysis was used to directly link calpeptin-sensitive calpain
      activity to calpain 10 splice variants. Rabbit, mouse, and rat kidney
      mitochondria contained 75kDa (calpain 10a), 56kDa (calpain 10c or 10d), and 50kDa
      (calpain 10e) splice variants. Interestingly, zymography yielded distinct bands
      of calpain activity containing multiple calpain 10 splice variants in all
      species. These results provide evidence that several previously postulated splice
      variants of calpain 10 are localized to the mitochondria in kidneys of rabbits,
      rats, and mice.

PMID- 18054327
TI  - Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by
      co-expression with SIRT5.
AB  - Yeast silent information regulator 2 (SIR2) is involved in extension of yeast
      longevity by calorie restriction, and SIRT3, SIRT4, and SIRT5 are mammalian
      homologs of SIR2 localized in mitochondria. We have investigated the localization
      of these three SIRT proteins of mouse. SIRT3, SIRT4, and SIRT5 proteins were
      localized in different compartments of the mitochondria. When SIRT3 and SIRT5
      were co-expressed in the cell, localization of SIRT3 protein changed from
      mitochondria to nucleus. These results suggest that the SIRT3, SIRT4, and SIRT5
      proteins exert distinct functions in mitochondria. In addition, the SIRT3 protein
      might function in nucleus.

PMID- 18054328
TI  - Minimization of a eukaryotic mini-intein.
AB  - Inteins are internal protein splicing elements that can autocatalytically self
      excise from their host protein and ligate the protein flanks (exteins) with a
      peptide bond. Large inteins comprise independent protein splicing and
      endonuclease domains whereas mini-inteins lack the central endonuclease domain.
      To identify mini-intein domains that are essential for protein splicing,
      deletions were introduced at different sites of the 157-aa PRP8 mini-intein of
      Penicillium chrysogenum. The removal of eight and six amino acids at two
      different sites resulted in a functional eukaryotic mini-intein of only 143 aa.

PMID- 18054329
TI  - The GC kinase Fray and Mo25 regulate Drosophila asymmetric divisions.
AB  - Drosophila neuroblasts provide an excellent model for asymmetric cell divisions,
      where cell-fate determinants such as Miranda localize at the basal cortex and
      segregate to one daughter cell. Mechanisms underlying this process, however,
      remain elusive. We found that Mo25 and the GC kinase Fray act in this regulation.
      mo25 and fray mutants show an indistinguishable defect in Miranda localization.
      On the other hand, Drosophila Mo25 interacts with the tumor suppressor kinase
      Lkb1 in vivo, as have shown in mammals. Overexpression of Lkb1, which accumulates
      in the cell cortex, drastically relocalizes both Mo25 and Fray from the cytoplasm
      to the cortex, causing the same phenotype as mo25-mutant neuroblasts. Recovery
      from this defect caused by Lkb1 overexpression requires simultaneous
      overexpression of Mo25 and Fray. We suggest from those results that Mo25 and Fray
      operate together or in the same pathway in Drosophila asymmetric processes, and
      that their function counterbalances Lkb1.

PMID- 18054330
TI  - UDP-glucuronosyltransferase 1A7 polymorphisms are associated with liver
      cirrhosis.
AB  - Variations in the UDP-glucuronosyltransferase (UGT) 1A7 gene have been found to
      be related to the development of hepatocellular carcinoma (HCC). Since the
      pathogenesis of liver cirrhosis is not dissimilar to that of HCC, we hypothesized
      that UGT1A7 genetic polymorphisms may be associated with liver cirrhosis. PCR
      restriction fragment length polymorphism was utilized to determine UGT for 1A7
      genotypes for the 159 patients with liver cirrhosis and 263 gender/age matched
      controls. Simple logistic regression analysis revealed that significant risk
      factors for liver cirrhosis were (1) hepatitis B virus (HBV) infection, (2)
      hepatitis C virus (HCV) infection, (3) HBV infection plus HCV infection and (4)
      low-activity UGT1A7 genotypes. The results of further multivariate logistic
      regression confirmed these associations. Interaction of low-activity UGT1A7
      genotypes and HBV (or HCV) infection produced an additive effect upon the risk
      for the development of liver cirrhosis [observed odds ratio (OR) (54.59) greater
      than the expected OR (18.05)]. UGT1A7 low/low genotype was also related to
      advanced liver cirrhosis (Child-Pugh classes C and/or B) (OR=7.50, P=0.009). This
      study demonstrates the novel findings that carriage of low-activity UGT1A7
      genotypes represents a risk factor for the development and functional severity of
      liver cirrhosis.

PMID- 18054331
TI  - The G501C polymorphism of oxidized LDL receptor gene [OLR-1] is associated with
      susceptibility and serum C-reactive protein concentration in Chinese essential
      hypertensives.
AB  - BACKGROUND: Oxidized LDL receptor gene 1 (OLR-1) polymorphism is reportedly
      associated with several cardiovascular conditions. However, its relationship with
      essential hypertension remains unknown. The aim of this study is to explore the
      association of OLR-1 polymorphism at position 501 in the open reading frame
      (G501C), with the susceptibility of essential hypertension. METHODS: 2-hundred
      eighty Chinese essential hypertensive and 284 control subjects were enrolled and
      genetic study was performed. The clinical data, i.e., sex, age, blood pressure,
      body mass index, smoking history, lipid profile and serum C-reactive protein
      concentration in both hypertensives and controls were obtained. RESULTS: A
      significant difference in OLR-1 genotype distributions was noted between the
      hypertensives and the controls (GG: 67.9% vs. 70.8%; GC: 20.0% vs. 23.6%; CC:
      12.1% vs. 5.6%, P=0.021). For G and C allele frequencies, the difference between
      these 2 groups was significant as well (G: 67.5% vs. 23.5%, C: 82.6% vs. 17.4%,
      P=0.011). Logistic regression analysis revealed that the CC genotype is an
      independent risk factor for hypertension (OR=3.036, 95% CI: 1.572-6.174,
      P=0.016). Furthermore, when the serum C-reactive protein concentration in the
      hypertensive group was studied according to OLR-1 genotypes, the serum CRP
      concentration in CC homozygous carriers were found significantly higher than that
      in GC and GG carriers (1.53+/-0.32, 1.31+/-0.32 and 2.94+/-1.29 respectively,
      P=0.002). CONCLUSIONS: The CC genotype of OLR-1 G501C polymorphism is associated
      with susceptibility and serum C-reactive protein concentration in Chinese
      essential hypertensive population.

PMID- 18054332
TI  - Letter to the Editor regarding a paper about HbA2 measurements on patients with
      HbS.

PMID- 18054333
TI  - Heterophilic antibody interference in a tryptase immunoassay.
AB  - OBJECTIVE: Investigation of the susceptibility of a tryptase immunoassay to
      interference by heterophilic antibodies. METHODS: The effect of preincubation
      with a blocking agent was investigated on the levels of tryptase, human anti
      mouse antibodies and IgM rheumatoid factor in sera with elevated IgM rheumatoid
      factor levels. RESULTS: In 5 of 30 sera with IgM rheumatoid factor, tryptase
      levels were reduced at least twofold after pre-incubation with blocking reagent.
      A significant association was observed between the presence of IgM rheumatoid
      factor in the sera and the interference of tryptase immunoassay. There was no
      quantitative correlation found between the reduction in serum tryptase level by
      treatment with a blocking agent, and the amount of IgM rheumatoid factor was
      present. However, this reduction in serum tryptase was significantly correlated
      with the amount of human anti-mouse antibodies in the sera. After incubation with
      blocking agent, there was no change in IgM Rheumatoid factor level, but a
      significant decrease in human anti-mouse antibodies. CONCLUSION: The Phadia
      tryptase assay method, in its present form, is sensitive to interference by
      heterophilic antibodies.

PMID- 18054334
TI  - Acute administration of 3,5-diiodo-L-thyronine to hypothyroid rats affects
      bioenergetic parameters in rat skeletal muscle mitochondria.
AB  - We investigated the mechanism by which 3,5-diiodo-l-thyronine (T2) affects
      skeletal muscle mitochondrial bioenergetic parameters following its acute
      administration to hypothyroid rats. One hour after injection, T2 increased both
      coupled and uncoupled respiration rates by +27% and +42%, respectively. Top-down
      elasticity analysis revealed that these effects were the result of increases in
      the substrate oxidation and mitochondrial uncoupling. Discriminating between
      proton-leak and redox-slip processes, we identified an increased mitochondrial
      proton conductance as the "pathway" underlying the effect of T2 on mitochondrial
      uncoupling. As a whole, these results may provide a mechanism by which T2 rapidly
      affects energy metabolism in hypothyroid rats.

PMID- 18054335
TI  - The physiological and pathophysiological role of adiponectin and adiponectin
      receptors in the peripheral tissues and CNS.
AB  - Adiponectin is an abundantly expressed adipokine in adipose tissue and has direct
      insulin sensitizing activity. A decrease in the circulating levels of adiponectin
      by interactions between genetic factors and environmental factors causing obesity
      has been shown to contribute to the development of insulin resistance, type 2
      diabetes, metabolic syndrome and atherosclerosis. In addition to its insulin
      sensitizing actions, adiponectin has central actions in the regulation of energy
      homeostasis. Adiponectin enhances AMP-activated protein kinase activity in the
      arcuate hypothalamus via its receptor AdipoR1 to stimulate food intake and
      decreases energy expenditure. We propose a hypothesis on the physiological role
      of adiponectin: a starvation gene in the course of evolution by promoting fat
      storage on facing the loss of adiposity.

PMID- 18054336
TI  - A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion.
AB  - A thorough understanding of histone acetyltransferase CBP/p300-mediated
      regulation of gene expression and cell growth is essential to identify mechanisms
      relevant to the development of histone deacetylase (HDAC) inhibitor-based
      preventive and therapeutic strategies. We found that knockdown of CBP/p300
      interacting coactivator with glutamic acid/aspartic acid-rich tail 2 (CITED2)
      increased colon cancer cell invasiveness in vitro. Gene expression profiling
      revealed that CITED2 knockdown induced matrix metalloproteinase-13 (MMP-13) gene
      expression in colon cancer cells. Butyrate, a naturally occurring HDAC inhibitor,
      induced CITED2 expression and downregulated MMP-13 expression in RKO cells.
      Additionally, ectopic expression of CITED2 arrested RKO cell growth. Thus, CITED2
      regulates colon cancer invasion and might be a target for HDAC inhibitor-based
      intervention of colon cancer.

PMID- 18054337
TI  - Phospho-mimicry mutant of atToc33 affects early development of Arabidopsis
      thaliana.
AB  - The precursor protein receptor at the chloroplast outer membrane atToc33 is a
      GTPase, which can be inactivated by phosphorylation in vitro, being arrested in
      the GDP loaded state. To assess the physiological function of phosphorylation,
      attoc33 knock out mutants were complemented with a mutated construct mimicking
      the constitutively phosphorylated state. Our data suggest that the reduced
      functionality of the mutant protein can be compensated by its upregulation.
      Chloroplast biogenesis and photosynthetic activity are impaired in the mutants
      during the early developmental stage, which is consistent with the requirement of
      atToc33 in young photosynthetic tissues.

PMID- 18054339
TI  - Evidence for the nucleosome-disruption process regulated by phosphorylation of
      120 kDa protein complex in Drosophila embryo cell-free system.
AB  - Using cell-free system derived from Drosophila embryos, we found evidence for a
      regulated nucleosome disruption process, which depends on the phosphorylation
      status of 120 kDa protein (complex). Dephosphorylation enables the remodeling
      activity to destabilize nucleosomes, which assume a more accessible structure,
      possessing increased DNase I sensitivity and high conformational flexibility of
      DNA; remodeling was more efficient on highly acetylated chromatin templates. This
      phosphorylation-regulated nucleosome destabilization, acting synergistically with
      histone acetylation, is discussed as a possible mechanism to provide regulated
      disrupt of histone-DNA interaction.

PMID- 18054338
TI  - The epidermal growth factor receptor (EGFR) is proteolytically modified by the
      Matriptase-Prostasin serine protease cascade in cultured epithelial cells.
AB  - Prostasin is expressed at the apical surface of normal epithelial cells and
      suppresses in vitro invasion of cancer cells. Prostasin re-expression in the PC-3
      prostate carcinoma cells down-regulated the epidermal growth factor receptor
      (EGFR) protein expression and EGF-induced phosphorylation of the extracellular
      signal-regulated kinases (Erk1/2). We report here that prostasin and its
      activating enzyme matriptase are capable of inducing proteolytic cleavages in the
      EGFR extracellular domain (ECD) when co-expressed in the FT-293 cells, generating
      two amino-terminally truncated fragments EGFR135 and EGFR110, at 135 and 110 kDa.
      Prostasin's role in EGFR cleavage is dependent on the serine active-site but not
      the GPI-anchor. The modifications of EGFR were confirmed to be on the primary
      structure by deglycosylation. EGFR135 and EGFR110 are not responsive to EGF
      stimulation, indicating loss of the ligand-binding domains. EGFR110 is
      constitutively phosphorylated and in its presence Erk1/2 phosphorylation is
      increased in the absence of EGF. The protease-induced EGFR cleavages are not
      dependent on EGFR phosphorylation. The EGFR ECD proteolytic modification by
      matriptase-prostasin is also observed in the BEAS-2B normal lung epithelial
      cells, the BPH-1 benign prostate hyperplasia and the MDA-MB-231 breast cancer
      cell lines; and represents a novel mechanism for epithelial cells to modulate EGF
      EGFR signaling.

PMID- 18054340
TI  - Effect of polyunsaturated fatty acids on endocannabinoid and N-acyl-ethanolamine
      levels in mouse adipocytes.
AB  - The tissue concentrations of the endocannabinoids, 2-arachidonoylglycerol (2-AG)
      and N-arachidonoyl-ethanolamine (anandamide), are altered in the adipose tissue
      of mice fed a high fat diet. We have investigated here the effect on
      endocannabinoid levels of incubation of mouse 3T3-F442A adipocytes with several
      free polyunstaurated fatty acids (PUFAs), including linolenic acid (LA), alpha
      linolenic acid (ALA), arachidonic acid (AA) and docosahexaenoic acid (DHA), as
      well as oleic acid (OA) and palmitic acid (PA). By using mass spectrometric
      methods, we quantified the levels of endocannabinoids, of two anandamide
      congeners, N-palmitoyl-ethanolamine (PEA) and N-oleoyl-ethanolamine (OEA), and of
      fatty acids esterified in triacylglycerols or phospholipids, which act as 2-AG
      and/or N-acyl-ethanolamine precursors. Incubation with AA strongly elevated 2-AG
      levels and the amounts of AA esterified in triacylglycerols and on glycerol
      carbon atom 2 (sn-2), but not 1 (sn-1), in phospholipids. Incubation with DHA
      decreased 2-AG and anandamide levels and the amounts of AA esterified on both the
      sn-2 and sn-1 position of phospholipids, but not on triacylglycerols. PEA levels
      augmented following incubation of adipocytes with OA and PA, with no
      corresponding changes in phospholipids and triacylglycerols. We suggest that
      dietary PUFAs might modulate the levels of adipocyte phospholipids that act as
      endocannabinoid precursors.

PMID- 18054341
TI  - Ionic interaction of myosin loop 2 with residues located beyond the N-terminal
      part of actin probed by chemical cross-linking.
AB  - To probe ionic contacts of skeletal muscle myosin with negatively charged
      residues located beyond the N-terminal part of actin, myosin subfragment 1 (S1)
      and actin split by ECP32 protease (ECP-actin) were cross-linked with 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC). We have found that unmodified S1 can be
      cross-linked not only to the N-terminal part, but also to the C-terminal 36 kDa
      fragment of ECP-actin. Subsequent experiments performed on S1 cleaved by elastase
      or trypsin indicate that the cross-linking site in S1 is located within loop 2.
      This site is composed of Lys-636 and Lys-637 and can interact with negatively
      charged residues of the 36 kDa actin fragment, most probably with Glu-99 and Glu
      100. Cross-links are formed both in the absence and presence of MgATP.P(i)
      analog, although the addition of nucleotide decreases the efficiency of the cross
      linking reaction.

PMID- 18054342
TI  - Isolation, purification, characterization and antigenic evaluation of GPI
      anchored membrane proteins from Leishmania (Viannia) braziliensis.
AB  - GPI-anchored proteins from the plasma membrane of Leishmania (Viannia)
      braziliensis promastigotes were isolated, characterized and their migration
      pattern compared with those from other Leishmania species. In all cases the SDS
      PAGE migration patterns were obtained under reducing and non-reducing conditions,
      using DL-dithiothreitol (DTT) as a reducer agent. Our results reveal that under
      reducing conditions the SDS-PAGE migration pattern is modified as a consequence
      of the disruption of disulphur-bonds and protein transformation. This is
      demonstrated when in non-reducing conditions the L. (V.) braziliensis-GPI
      anchored proteins pattern showed a group of bands over the 100kDa, and two more
      bands of 52kDa and 50kDa in four different isolates, whereas under reducing
      conditions the major GPI-anchored protein fractions were detected as bands of
      63kDa, 50kDa and an increase of peptides between 34kDa and 22kDa. Similar
      modifications were detected in the SDS-PAGE migration patterns of GPI-anchored
      protein fractions from L. (Leishmania) donovani, L. (L.) mexicana and L. (L.)
      amazonensis run under the same reducing conditions. Antigenic evaluation carried
      out by Western blot revealed the presence of two very specific L. (V.)
      braziliensis-GPI-anchored protein bands of 50kDa and 28kDa. These bands were
      specifically recognized by anti-L. (V.) braziliensis-GPI-anchored protein serum
      from experimentally immunized animals. These two peptides were not detected when
      GPI-anchored protein fractions from L. (L.) donovani, L. (L.) mexicana and L.
      (L.) amazonensis, were challenged with the same anti-serum. The present results
      lead us to suggest the use of these two peptides as biochemical markers to
      identify and differentiate leishmaniasis caused by L. (V.) braziliensis. The lack
      of immunogenicity observed here with the peptide gp63, a very common protein
      detected in Leishmania species, is considered.

PMID- 18054343
TI  - [Evolution of the surgical strategy in hypertrophic cardiomyopathy: case studies
      of eight patients].
AB  - INTRODUCTION: Hypertrophic cardiomyopathy is an inherited disease characterized
      by a left ventricular hypertrophy, a diastolic dysfunction and rhythm troubles
      with risk of sudden death. There was an evolution in the surgical strategy to
      treat the patients who present a left ventricular outflow tract gradient.
      MATERIALS AND METHODS: A retrospective study was conducted: We selected eight
      cases who presented an hypertrophic cardiomyopathy and operated on. Pre and post
      operative echocardiographic data were analysed. Follow up was obtained by call or
      mail to the cardiologist. RESULTS: The patients were classified in four groups:
      isolated left ventricular outflow tract obstruction, left ventricular outflow
      tract obstruction and associated lesions, obstructive hypertrophic cardiomyopathy
      and endocarditis, post operative complications of the hypertrophic cardiomyopathy
      surgery. We observed a significant decrease of the left ventricular outflow tract
      mean gradient in the post operative period and at four years. CONCLUSION:
      Surgical management of obstructive hypertrophic cardiomyopathy remain an
      important option in young patients, in case of failure of the ethanol septal
      ablation or in patients who present other surgical lesions. The dual chamber
      stimulation remain indicated in old patients.

PMID- 18054344
TI  - [Results of the surgical closure of ventricular septal defects of various ages:
      report of 30 cases].
AB  - OBJECTIVE: To appreciate short and midterm results of patients after surgical
      closure of the ventricular septal defect. MATERIAL AND METHODS: The study is
      retrospective and took place in the department of cardiovascular surgery "B", Ibn
      Sina hospital, Rabat, Morocco. Between 1995 and 2005, 30 patients underwent a
      surgical closure of ventricular septal defect. Eighteen patients (60%) were males
      and twelve (40%) were females with a mean age of 10 years (18 months-36 years).
      Seven patients (23%) were older than 16 years. All of ventricular septal defects
      were type 2, unique and most of them perimembranous (70%). Four patients (13%),
      were older than 16 years, had a significant aortic insufficiency that has
      dictated the aortotomy for ventricular septal defect repair. The surgical
      approach through the right atriotomy was sufficient for complete repair in 22
      patients (73%). Closure of the defect has been done using a pericardial
      autologous patch in 28 patients (93%). RESULTS: No operative mortality was
      observed. The mean follow-up was five years. Eight patients (26%) had a residual
      ventricular septal defect that progressed to spontaneous closure. Two patients
      (6%) had a residual pulmonary hypertension and two others a moderate aortic
      regurgitation. The four patients were older than 16 years. Echocardiography
      showed a significant reduction in left ventricular dimension and systolic
      pulmonary artery pressure. At last follow-up, 87% of the patients were in NYHA
      class 1. CONCLUSION: This study demonstrates that surgical closure of ventricular
      septal defect ensures a good outcome in short and midterm. Nevertheless, the risk
      of delayed complications justifies long-term and regular follow-up.

PMID- 18054345
TI  - [Risk factors of stroke among Congolese black hypertensive diabetics].
AB  - BACKGROUND: The relationship between diabetes mellitus and risk of stroke is well
      established. This risk is more elevated for hypertensive diabetics men.
      OBJECTIVE: To determine the incidence and the risk factors of stroke among
      hypertensive diabetics. METHODS: This prospective study has considered baseline
      demographic, behavioural and biological parameters collected in 2002 among black
      Congolese hypertensive diabetics from Kinshasa till the onset of stroke or not in
      2006. RESULTS: Out of 492 followed-up patients (279 women, 213 men, 57+/-10
      years), 41.9% were old of age > or = 60 years, and 16.5% experienced acute
      stroke. In univariate analysis, a significant association between age > or = 60
      years, cigarette smoking, excessive alcohol intake, diabetes duration > or = 2
      years, pulse pressure > or = 60 mmHg, acute bacterian pneumonia, left ventricule
      hypertrophy, hypertensive retinopathy, diabetic retinopathy, diabetic foot,
      diabetic neuropathy, congestive heart failure, chronic renal failure, lack of
      diabetic treatment compliance and the occurrence of acute stroke. However,
      multivariate analysis identified only acute bacterian pneumonia, diabetic
      retinopathy, diabetic neuropathy, chronic renal failure and pulse pressure > or =
      60 mmHg as the independent risk factors of stroke onset among these black
      congolese hypertensive diabetics with the following and respective values of
      relative risk (hazard ratio): 6,2 (IC 95%: 3.2 to 11.9; P<0.0001), 2,2 (IC 95%:
      1.2 to 4.1; P<0.01), 3.6 (IC 95%: 1.9 to 6.8; P<0.0001), 6.4 (IC 95%: 2.9 to
      14.1; P<0.01) and 4.1 (IC 95%: 1.6 to 10.3; P<0.0001). CONCLUSION: The rate of
      stroke onset is high among these hypertensive diabetics. This is the consequence
      of independent and respective action of infection, diabetic retinopathy, diabetic
      neuropathy, chronic renal failure and arterial stiffness.

PMID- 18054346
TI  - [Myocarditis caused by Trichinella spiralis: a case report].
AB  - Trichinellosis is a cosmopolitan nematodosis which is rare in the developed
      countries. Myocarditis represents the most frequent form of cardiac
      complications, sometimes lethal. The authors report the observation of a 36-years
      old patient admitted for trichinellosis, who presented asymptomatic
      electrocardiographic modifications and a rise in the troponine I. The magnetic
      resonance imaging (MRI) after gadolinium injection, highlighted an underepicardic
      late raising rendering the diagnosis of myocarditis highly probable. The
      paraclinic anomalies were corrected gradually under antiparasitarian treatment.
      Besides the EKG, the MRI is a non-invasive and repetitive method allowing as well
      the positive diagnosis as the follow-up of those patients.

PMID- 18054347
TI  - Role of P-glycoprotein in accumulation and cytotoxicity of amrubicin and
      amrubicinol in MDR1 gene-transfected LLC-PK1 cells and human A549 lung
      adenocarcinoma cells.
AB  - Amrubicin is a completely synthetic 9-aminoanthracycline agent for the treatment
      of lung cancer in Japan. The cytotoxicity of C-13 hydroxy metabolite,
      amrubicinol, is 10 to 100 times greater than that of amrubicin. The transporters
      responsible for the intracellular pharmacokinetics of amrubicin and amrubicinol
      remains unclear. This study was aimed to determine whether P-glycoprotein (P-gp)
      plays functional and preventive role in cellular accumulation and cytotoxicity of
      amrubicin and its active metabolite amrubicinol by in vitro transport and
      toxicity experiments. Cytotoxicity and intracellular accumulation of amrubicin
      and amrubicinol were evaluated by LLC-PK1 cells, MDR1 gene-transfected LLC-PK1 (L
      MDR1) cells overexpressing P-gp, and human A549 lung adenocarcinoma cells. L-MDR1
      cells showed 6- and 12-fold greater resistance to amrubicin and amrubicinol,
      respectively, than the parental LLC-PK1 cells. The intracellular accumulation of
      both drugs in L-MDR1 cells was significantly reduced compared to the LLC-PK1
      cells. The basal-to-apical transepithelial transport of both drugs markedly
      exceeded, whereas the apical-to-basal transport of both drugs was significantly
      lower in L-MDR1 cells than LLC-PK1 cells. Cyclosporin A (CyA) restored the
      sensitivity, intracellular accumulation and transport activity for both drugs in
      L-MDR1 cells. In A549 cells, CyA significantly increased the intracellular
      accumulation and cytotoxicity of both drugs. These findings indicated that P-gp
      is responsible for cellular accumulation and cytotoxicity of both amrubicin and
      amrubicinol, therefore suggesting that the antitumor effect of amrubicin could be
      affected by the expression level of P-gp in lung cancer cells in chemotherapeutic
      treatments.

PMID- 18054348
TI  - Promiscuous coupling and involvement of protein kinase C and extracellular signal
      regulated kinase 1/2 in the adenosine A1 receptor signalling in mammalian
      spermatozoa.
AB  - Mammalian spermatozoa require a maturational event after ejaculation that allows
      them to acquire the capacity for fertilisation. This process occurs spontaneously
      during the transit through the female reproductive tract where spermatozoa are in
      contact with micromolar concentrations of adenosine that might act as a
      capacitative effector. This study shows that the adenosine A1 receptor agonist, 2
      chloro-N6-cyclopentyladenosine, can induce capacitation, i.e., the ability to
      undergo the acrosome reaction and to become fertile. This receptor, already known
      to be bound to Galpha(i2), is also bound to G(q/11). These G proteins are
      functional in the signalling pathway elicited by the A1 receptor and correlate
      with the multiple intracellular events that follow its activation. The use of
      protein kinase C isoform inhibitors and MEK inhibitors, resulting in the
      abolition of the biological response to the selective agonist, indicates the
      involvement of protein kinase C and MEK in its signalling. In agonist-treated
      spermatozoa an extracellular calcium influx, involvement of alpha and gamma PKC
      isoforms and transient phosphorylation of ERK1/2 have been observed. Our results,
      besides showing that adenosine A1 receptor prompts mammalian spermatozoa to
      undergo the acrosome reaction hence supporting a role for adenosine as agent for
      fertilisation, show that 2-chloro-N6-cyclopentyladenosine triggers signalling
      mechanisms that involve both Galpha(i2) and G(q/11), extracellular calcium
      influx, modulation of classical Ca2+-dependent PCK isoforms and up-regulation of
      the ERK1/2 phosphorylation.

PMID- 18054349
TI  - Structural studies of a methyl galacturonosyl-methoxyxylan isolated from the stem
      of Lagenaria siceraria (Lau).
AB  - A water-soluble polysaccharide was isolated from the aqueous extract of the stem
      of Lagenaria siceraria. The polysaccharide was found to be constituted of methyl
      d-galacturonate, 2-O-methyl-D-xylose, and d-xylose in a ratio of 1:1:1. On the
      basis of total acid hydrolysis, methylation analysis, periodate oxidation, NMR
      studies ((1)H, (13)C, 2D-COSY, TOCSY, NOESY, HSQC, and HMBC), and MALDI-TOF MS
      analysis, the structure of the repeating unit of the polysaccharide is determined
      as.

PMID- 18054350
TI  - Two novel aminooligosaccharides isolated from the culture of Streptomyces
      coelicoflavus ZG0656 as potent inhibitors of alpha-amylase.
AB  - Two novel aminooligosaccharides were separated from the culture filtrate of
      Streptomyces coelicoflavus ZG0656. Their chemical structures were determined by
      electrospray ionization tandem mass spectrometry (ESI-MS/MS) and 2D nuclear
      magnetic resonance (NMR) spectroscopy. Because of their acarviosine core
      structures, the names acarviostatins II23 and II13 were given to the novel
      compounds. The two acarviostatins were both mixed noncompetitive inhibitors of
      porcine pancreatic alpha-amylase (PPA), with inhibition constants (K(i)) of 0.009
      microM (acarviostatin II23) and 0.010 microM (acarviostatin II13). Therefore,
      acarviostatin II23 and acarviostatin II13 are, respectively, 231 and 208 times
      more potent than acarbose.

PMID- 18054351
TI  - Heterogeneity in iota-carrageenan molecular structure: insights for polymorph II-
      >III transition in the presence of calcium ions.
AB  - Iota-carrageenan is used in pharmaceutical and food applications due to its
      ability to complex with other hydrocolloids and proteins. Six distinct cation
      dependent allomorphs, consistent with its versatile functionality, have so far
      been observed in the solid state. In this contribution, X-ray structural details
      of calcium iota-carrageenan (form III) are reported. The polysaccharide retains
      the half-staggered, parallel, 3-fold, right-handed double helix stabilized by
      interchain hydrogen bonds from O-2H and O-6H in the Galp units. Results show that
      there are four helices, rather than one in I or three in II, organized in a
      larger pseudo-trigonal unit cell of dimensions a=27.44, c=13.01 A, and gamma=120
      degrees . The four helices have similar core structures, but their sulfate group
      orientations are quite different. Fifteen calcium ions and 64 water molecules
      hold the helices together and promote helix-helix interactions. The results
      portray how the helices would shuffle around in an orchestrated manner to yield
      calcium iota-carrageenan III from II.

PMID- 18054352
TI  - Oral eicosapentaenoic acid supplementation as possible therapy for endometriosis.
AB  - OBJECTIVE: To investigate the anti-inflammatory effect of n-3 eicosapentaenoic
      acid (EPA) compared with n-6 linoleic acid (LA) in an endometriosis rat model. We
      focused on the relationship between lipid metabolism and inflammatory reactions
      in endometriosis based on the hypothesis that a lipid intake imbalance is one of
      the factors responsible for the recent increase of endometriosis. DESIGN:
      Prospective, randomized experimental study. SETTING: Animal surgery laboratory in
      a university hospital. ANIMAL(S): Sprague-Dawley rats (female, 6 weeks old).
      INTERVENTION(S): Rats were fed a diet with EPA (n = 9) or with LA (n = 9) for 2
      weeks. Two weeks after feeding, the uterus was autotransplanted to the peritoneum
      to construct an endometriosis model. Feeding was continued for a total of 6
      weeks. Two and 4 weeks after autotransplantation, three rats of each group were
      killed and evaluated. MAIN OUTCOME MEASURE(S): Endometriotic lesions were
      morphologically evaluated and their fatty acid composition was examined. Gene
      expression in these tissues was evaluated by cDNA microarray analysis and
      quantative real-time reverse transcriptase-polymerase chain reaction (RT-PCR).
      RESULT(S): In the EPA group, the n-3:n-6 ratio in each tissue significantly
      increased and the thickening of the interstitium, an active site for inflammation
      in endometriosis, was significantly suppressed (0.30 +/- 0.09 mm [EPA group] vs.
      0.77 +/- 0.23 mm [LA group]). The mRNA of metalloproteinases, interleukin-1beta,
      interleukin-1r, prostaglandin E synthase (Ptges), and nuclear factor (NF)-kappaB
      were reduced in the EPA group. CONCLUSION(S): EPA supplementation might be a
      valid strategy for the treatment of endometriosis.

PMID- 18054353
TI  - Growth hormone and its receptor in human ovaries from fetuses and adults.
AB  - OBJECTIVE: To investigate the presence of growth hormone (GH) and its receptor
      (GH-R) in early developing follicles. DESIGN: Immunocytochemical and in situ
      hybridization study. SETTING: Major tertiary care and referral academic centers.
      PATIENT(S): Ten ovarian samples from adults/girls aged 6-38 years and from 10
      fetuses of women undergoing second and third trimester pregnancy terminations.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Immunocytochemistry and in situ
      hybridization on paraffin sections of human ovaries from fetuses and women/girls.
      RESULT(S): The proteins and the mRNA transcripts for GH and GH-R were detected in
      oocytes, granulosa (GC), and stroma cells from both sources (fetuses and
      women/girls), with low staining intensity only in a portion of the fetal GC.
      CONCLUSION(S): This is the first report of the expression of GH-R in human
      ovaries from fetuses as well as women/girls and of GH in human fetal ovaries. Be
      that as it may, further experiments should be conducted to elucidate if indeed GH
      is involved in the initiation of human primordial follicular growth.

PMID- 18054354
TI  - Robotic tubal anastomosis: surgical technique and cost effectiveness.
AB  - OBJECTIVE: To evaluate the feasibility of robotic microsurgical tubal anastomosis
      and compare the results and cost effectiveness with the same procedure performed
      by laparotomy. DESIGN: Prospective cohort study. SETTING: University hospital.
      PATIENT(S): Patients with a history of bilateral tubal ligation who desired
      reversal for future fertility. INTERVENTION(S): Tubal anastomoses through either
      a robotic approach or through a laparotomy. MAIN OUTCOME MEASURE(S): Operative
      times, hospitalization, complications, postoperative patency, clinical outcomes,
      and the cost per live birth. RESULT(S): The mean operative time for robotic
      anastomoses was statistically significantly greater than open anastomoses (ROBOT
      201 minutes; OPEN 155.3 minutes), although hospitalization times were
      statistically significantly shorter (ROBOT 4 hours; OPEN 34.7 hours). The return
      to instrumental activities of daily living was accelerated in the patients who
      had undergone a robotic anastomosis (ROBOT 11.1 days; OPEN 28.1 days). Although
      this was a small series, the pregnancy rates were comparable between groups
      (ROBOT 62.5%; OPEN 50%), yet the rate of abnormal pregnancy was higher in the
      robotic group (ectopic: ROBOT 4, OPEN 1; spontaneous pregnancy loss: ROBOT 2,
      OPEN 1). The cost per delivery was similar between the groups (ROBOT $92,488.00,
      OPEN $92,205.90). CONCLUSION(S): Robotically assisted laparoscopic microsurgical
      tubal anastomosis is feasible and cost effective with results that are comparable
      with the traditional open approach.

PMID- 18054355
TI  - Purification and analysis of DNases of Tritrichomonas foetus: evidence that these
      enzymes are glycoproteins.
AB  - Tritrichomonas foetus is the causative agent of trichomoniasis. In cattle,
      infection results in economic losses to the beef and dairy industries due to
      abortion and infertility. Soluble DNases of T. foetus that play a role in
      pathogenesis and are potential therapeutic targets, were extracted and purified
      utilising lectin affinity chromatography. The DNases were bound to and eluted
      from Concanavalin A (Con A)-sepharose indicating that they are glycoproteins with
      alpha-linked mannose or glucose residues. The nature of the glycans carried on
      the eluted proteins in the fraction containing DNase activity was assessed using
      an enzyme-linked lectin assay. The lectin binding studies predict the presence of
      both N- and O-type glycans. Manganese was a potent (33%) activator of the
      DNase(s) whereas zinc inhibited enzyme activity by approximately 66%. The
      DNase(s) had a pH optimum of 4 and a molecular weight of 160 kDa. The DNase(s)
      were able to completely degrade DNA from animal, plant, fungal, yeast and
      bacterial sources, but did not significantly degrade RNA.

PMID- 18054356
TI  - Chickens (Gallus domesticus) are natural intermediate hosts of Neospora caninum.
AB  - Neospora caninum naturally infects many mammal species, but has not previously
      been demonstrated in birds. We examined sera for N. caninum antibodies from 200
      outdoor chickens and from 200 chickens confined indoors in the state of Bahia,
      Brazil. Seroprevalence was greater in outdoor chickens (23.5% versus 1.5%,
      P<0.001). PCR testing for N. caninum was positive in six of 10 seropositive
      chickens. Amplicons from two of these were sequenced and had 97-98% nucleotide
      identity with N. caninum. This finding extends the list of intermediate hosts of
      N. caninum to include birds and may have important epidemiological consequences.

PMID- 18054358
TI  - siRNA silencing reveals role of vascular cell adhesion molecule-1 in vascular
      smooth muscle cell migration.
AB  - Vascular cell adhesion molecule-1 (VCAM-1) is an adhesion molecule expressed by
      endothelial cells for recruitment of leukocytes during inflammation. It is also
      abundantly expressed by smooth muscle cells in atherosclerotic lesions and in
      injured arteries. In this study, we examined the role of VCAM-1 in smooth muscle
      cell migration. Smooth muscle cells were isolated from the aorta of C57BL/6 mice
      and transfected with short interfering RNAs (siRNAs) targeting VCAM-1. Inhibition
      on VCAM-1 expression by siRNAs was assessed by Western blot analysis, RT-PCR and
      by measuring soluble VCAM-1 concentrations in the incubation medium. One siRNA
      that showed greater suppression on VCAM-1 expression was used for migration
      assay. A single scratch wound was made on 70% confluent cells and cells migrated
      from wounded monolayer were counted 24 and 48h after injury. Treatment with VCAM
      1 siRNA resulted in a significant reduction in the number of migrated cells. This
      siRNA also exhibited a minor effect on smooth muscle cell proliferation. Thus,
      our findings indicate that VCAM-1 is necessary for the migration of smooth muscle
      cells and interfering VCAM-1 expression could be an effective approach to
      prevention and treatment of atherosclerosis and restenosis.

PMID- 18054357
TI  - Inhibition of intestinal absorption of cholesterol by ezetimibe or bile acids by
      SC-435 alters lipoprotein metabolism and extends the lifespan of SR-BI/apoE
      double knockout mice.
AB  - SR-BI/apoE double knockout (dKO) mice exhibit many features of human coronary
      heart disease (CHD), including hypercholesterolemia, occlusive coronary
      atherosclerosis, cardiac hypertrophy, myocardial infarctions, cardiac dysfunction
      and premature death. Ezetimibe is a FDA-approved, intestinal cholesterol
      absorption inhibitor that lowers plasma LDL cholesterol in humans and animals and
      inhibits aortic root atherosclerosis in apoE KO mice, but has not been proven to
      reduce CHD. Three-week-ezetimibe treatment of dKO mice (0.005% (w/w) in standard
      chow administered from weaning) resulted in a 35% decrease in cholesterol in
      IDL/LDL-size lipoproteins, but not in VLDL- and HDL-size lipoproteins. Ezetimibe
      treatment significantly reduced aortic root (57%) and coronary arterial (68%)
      atherosclerosis, cardiomegaly (24%) and cardiac fibrosis (57%), and prolonged the
      lives of the mice (27%). This represents the first demonstration of beneficial
      effects of ezetimibe treatment on CHD. The dKO mice were similarly treated with
      SC-435 (0.01% (w/w)), an apical sodium codependent bile acid transporter (ASBT)
      inhibitor, that blocks intestinal absorption of bile acids, lowers plasma
      cholesterol in animals, and reduces aortic root atherosclerosis in apoE KO mice.
      The effects of SC-435 treatment were similar to those of ezetimibe: 37% decrease
      in ILD/LDL-size lipoprotein cholesterol and 57% prolongation in median lifespan.
      Thus, inhibition of intestinal absorption of either cholesterol (ezetimibe) or
      bile acids (SC-435) significantly reduced plasma IDL/LDL-size lipoprotein
      cholesterol levels and improved survival of SR-BI/apoE dKO mice. The SR-BI/apoE
      dKO murine model of atherosclerotic occlusive, arterial CHD appears to provide a
      useful system to evaluate compounds that modulate cholesterol homeostasis and
      atherosclerosis.

PMID- 18054359
TI  - Infection and inflammation decrease apolipoprotein M expression.
AB  - Inflammation can produce abnormalities that could increase the risk for
      atherosclerosis including alterations in lipid and lipoprotein metabolism.
      Apolipoprotein M is a recently described HDL-associated apoprotein expressed
      mainly in the liver and kidney with protective effects against atherosclerosis.
      In this study, we describe the regulation of apolipoprotein M during the acute
      phase response. Stimuli that produce systemic inflammation, LPS, zymosan, or
      turpentine, decrease apolipoprotein M mRNA levels in the liver and kidney.
      Treatment of Hep3B hepatoma cells with TNF or IL-1 also decreased apolipoprotein
      M mRNA levels. The decrease in apolipoprotein M mRNA leads to a decrease in
      apolipoprotein M secretion into the media in Hep3B cells and a decrease in mouse
      serum following LPS administration. Moreover, in humans with acute bacterial
      infections or chronic HIV infection, serum apolipoprotein M levels are decreased.
      Apolipoprotein M is a negative acute response protein that decreases during
      infection and inflammation. These results are consistent with the finding that
      infections and inflammatory disorders accompanied by systemic inflammation are
      associated with an increased risk of atherosclerosis.

PMID- 18054360
TI  - Metalloproteinase inhibition ameliorates hypertension and prevents vascular
      dysfunction and remodeling in renovascular hypertensive rats.
AB  - Altered activity of matrix metalloproteinases (MMPs) is implicated in the
      vascular remodeling of hypertension. We examined whether increased MMP-2
      expression/activity plays a role in the vascular remodeling and dysfunction found
      in the two-kidney, one-clip (2K-1C) hypertension. Sham operated or 2K-1C
      hypertension rats were treated with doxycycline 30mg/(kgday) (or vehicle).
      Systolic blood pressure was monitored weekly. After 8 weeks of treatment, aortic
      rings were isolated to assess endothelium-dependent and independent relaxations.
      Quantitative morphometry of structural changes, collagen, and elastin contents in
      the aortic wall were studied in hematoxylin/eosin, Sirius Red, and Orceine
      stained aortic sections, respectively. Aortic MMP-2 levels were determined by
      gelatin zymography and aortic MMP-2 proteolytic activity was measured using DQ
      gelatin as the substrate after MMP-2 was captured by a specific antibody and
      immobilized on a microplate. Aortic MMP-2/tissue inhibitor of metalloproteinases
      (TIMP)-2 mRNA levels were determined by real time RT-PCR. Doxycycline attenuated
      2K-1C hypertension (215+/-8mmHg versus 167+/-13mmHg in 2K-1C rats and 2K-1C+doxy
      rats, respectively; P<0.01) and prevented the 35% reduction in endothelium
      dependent vasorelaxation found in 2K-1C rats. Doxycycline prevented the increases
      in media thickness, and was associated with lower media/lumen and cross-sectional
      areas (all P<0.01). Doxycycline also prevented excessive collagen and elastin
      deposition in the vascular wall. Increased MMP-2 and Pro-MMP-2 levels and MMP-2
      activity were found in the aortas of 2K-1C rats (all P<0.05). A 21-fold increase
      (P<0.001) in the ratio of MMP-2/TIMP-2 mRNA expression was found in the 2K-1C
      group, whereas this ratio remained unaltered in 2K-1C+doxy rats. Our results
      suggest that MMP-2 plays a role in 2K-1C hypertension and its structural and
      functional vascular changes, which were attenuated by doxycycline.

PMID- 18054361
TI  - Serum levels of the atherosclerosis biomarker sTWEAK are decreased in type 2
      diabetes and end-stage renal disease.
AB  - Recently, circulating soluble tumor necrosis factor-like weak inducer of
      apoptosis (sTWEAK) was introduced as a potential biomarker which is downregulated
      in atherosclerosis. In the current study, we hypothesized that sTWEAK serum
      levels are decreased in end-stage renal disease and in patients with type 2
      diabetes mellitus (T2DM) since both conditions are high-risk states for
      atherosclerotic disease. Soluble TWEAK was quantified by ELISA in control
      patients (n=60) with a glomerular filtration rate above 50 ml/min and patients on
      chronic hemodialysis (CD, n=60) and correlated to clinical and biochemical
      measures of renal function, glucose, and lipid metabolism, as well as
      inflammation. 30 control patients and 32 CD patients presented with T2DM. Mean
      serum sTWEAK concentrations were significantly lower in CD and T2DM patients with
      lowest concentrations seen when both conditions were present (control/-T2DM: 669
      +/- 201 microg/l; control/+T2DM: 516 +/- 187 microg/l; CD/-T2DM: 402 +/- 128
      microg/l; CD/+T2DM: 317 +/- 132 microg/l; all comparisons between groups p<0.05).
      In univariate analyses, sTWEAK was negatively correlated with fasting glucose in
      both, control and CD patients. In multivariate analyses, CD and T2DM remained
      independently associated with circulating sTWEAK. Taken together, circulating
      sTWEAK concentrations are decreased in end-stage renal disease and T2DM.
      Furthermore, both conditions have an additive and independent negative effect on
      sTWEAK levels. Our results support the view that circulating sTWEAK might be a
      novel biomarker of atherosclerosis.

PMID- 18054363
TI  - Modelling swimmers' speeds over the course of a race.
AB  - A stochastic model of swimming speed over the course of a male 200m freestyle
      swimming race is proposed. It builds on a dynamical model reflecting the trade
      off between drag and propulsion in swimming. The parameters of the model are
      estimated from elapsed time data observed at several points along the pool. The
      model fits the data well and also provides a good description of the swimming
      strategies of each swimmer from phase to phase in the race. An individual factor
      measuring how much faster or slower the individual swims relative to the average
      swimming speed of the race is simultaneously estimated in the course of fitting
      the model. This factor is, as expected, closely related to the final outcome of
      the race.

PMID- 18054362
TI  - In situ friction measurement on murine cartilage by atomic force microscopy.
AB  - Articular cartilage provides a low-friction, wear-resistant surface for the
      motion of diarthrodial joints. The objective of this study was to develop a
      method for in situ friction measurement of murine cartilage using a colloidal
      probe attached to the cantilever of an atomic force microscope. Sliding friction
      was measured between a chemically functionalized microsphere and the cartilage of
      the murine femoral head. Friction was measured at normal loads ranging
      incrementally from 20 to 100 nN with a sliding speed of 40 microm/s and sliding
      distance of 64 microm. Under these test conditions, hydrostatic pressurization
      and biphasic load support in the cartilage were minimized, providing frictional
      measurements that predominantly reflect boundary lubrication properties. Friction
      coefficients measured on murine tissue (0.25+/-0.11) were similar to those
      measured on porcine tissue (0.23+/-0.09) and were in general agreement with
      measurements of boundary friction on cartilage by other researchers. Using the
      colloidal probe as an indenter, the elastic mechanical properties and surface
      roughness were measured in the same configuration. Interfacial shear was found to
      be the principal mechanism of friction generation, with little to no friction
      resulting from plowing forces, collision forces, or energy losses due to normal
      deformation. This measurement technique can be applied to future studies of
      cartilage friction and mechanical properties on genetically altered mice or other
      small animals.

PMID- 18054364
TI  - Multi-screening approach to monitor and quantify 42 antibiotic residues in honey
      by liquid chromatography-tandem mass spectrometry.
AB  - A multi-screening approach for monitoring potential chemical contaminants in
      honey by liquid chromatography-electrospray ionization tandem mass spectrometry
      (LC-ESI-MS/MS) has been developed. A total of 42 veterinary drugs (5
      tetracyclines, 7 macrolides, 3 aminoglycosides, 8 beta-lactams, 2 amphenicols and
      17 sulfonamides) were surveyed with the ultimate goal of unambiguously confirmed
      and quantified these analytes at a concentration level of 20 microg/kg. A basic
      sample preparation including four subsequent liquid/liquid extraction steps was
      necessary to adequately extract the compounds of interest from the honey. The
      four extracts were injected into the LC-ESI-MS/MS using a stacking injection
      procedure. Validation of the entire procedure was carried out according to the
      European Union directive 2002/657/EC at three concentration levels, i.e., 10, 20
      and 30 microg/kg. Good performance data were obtained for 37 analytes, out of the
      42 studied. Limit of compliance and detection limit were calculated based on an
      internal limit set at 20 microg/kg for all the compounds and ranged between 24-30
      and 27-80 microg/kg, respectively. A limited survey on honeys of different
      geographical origins has demonstrated that positive honey samples were often
      contaminated by more than one class of drugs, thus highlighting the usefulness of
      such multi-screening approach to ensure and warrants the quality of honey.

PMID- 18054365
TI  - Is a "Phoenician" reading style superior to a "Chinese" reading style? Evidence
      from fourth graders.
AB  - This study compared normally achieving fourth-grade "Phoenician" readers, who
      identify nonwords significantly more accurately than they do exception words,
      with "Chinese" readers, who show the reverse pattern. Phoenician readers scored
      lower than Chinese readers on word identification, exception word reading,
      orthographic choice, spelling, reading comprehension, and verbal ability. When
      compared with normally achieving children who read nonwords and exception words
      equally well, Chinese readers scored as well as these children on word
      identification, regular word reading, orthographic choice, spelling, reading
      comprehension, phonological sensitivity, and verbal ability and scored better on
      exception word reading. Chinese readers also used rhyme-based analogies to read
      nonwords derived from high-frequency exception words just as often as did these
      children. As predicted, Phoenician and Chinese readers adopted somewhat different
      strategies in reading ambiguous nonwords constructed by analogy to high-frequency
      exception words. Phoenician readers were more likely than Chinese readers to read
      ambiguous monosyllabic nonwords via context-free grapheme-phoneme correspondences
      and were less likely to read disyllabic nonwords by analogy to high-frequency
      analogues. Although the Chinese reading style was more common than the Phoenician
      style in normally achieving fourth graders, there were similar numbers of poor
      readers with phonological dyslexia (identifying nonwords significantly more
      accurately than exception words) and surface dyslexia (showing the reverse
      pattern), although surface dyslexia was more common in the severely disabled
      readers. However, few of the poor readers showed pure patterns of phonological or
      surface dyslexia.

PMID- 18054366
TI  - Simple quasispecies models for the survival-of-the-flattest effect: The role of
      space.
AB  - The survival-of-the-flattest effect postulates that under high mutation rates
      natural selection does not necessarily favor the faster replicators. Under such
      conditions, genotypes which are robust against deleterious mutational effects may
      be favored instead, even at the cost of a slower replication. This tantalizing
      hypothesis has been recently proved using digital organisms, subviral RNA plant
      pathogens (viroids), and an animal RNA virus. In this work we study a simple
      theoretical system composed by two competing quasispecies which are located at
      two widely different fitness landscapes that represent, respectively, a fit and a
      flat quasispecies. The fit quasispecies is characterized by high replication rate
      and low mutational robustness, whereas the flat quasispecies is characterized by
      low replication rate but high mutational robustness. By using a mean field model,
      in silico simulations with digital replicons and a two-dimensional spatial model
      given by a stochastic cellular automata (CA), we predict the presence of an
      absorbing first-order phase transition with critical slowing down between
      selection for replication speed and selection for mutational robustness, where
      the surpassing of a critical mutation rate involves the outcompetition of the fit
      quasispecies by the flat one. Furthermore, it is shown that space, which involves
      a lower critical mutation rate, broadens the conditions at which the survival-of
      the-flattest may occur.

PMID- 18054367
TI  - Mechanisms of telomerase-dimer catalysis.
AB  - There is evidence that human telomerase acts as a dimer [Wenz, C., Enenkel, B.,
      Amacker, M., Kelleher, C., Damm, K., Lingner, J., 2001. Human telomerase contains
      two cooperating telomerase RNA molecules. EMBO J. 20, 3526-3534]. Three possible
      mechanisms have been proposed. We translate those proposals into three detailed
      mechanistic models for telomerase action, also introducing optional
      isomerizations with equilibrium constants inversely related to the number of
      bound nucleotides. To distinguish between these models by in situ experiments we
      propose a microscopic system which uses two-photon excitation of fluorescence in
      a volume of about 0.5 microm(3). A variety of detection strategies and
      experimental designs are considered; we focus on those best suited to observation
      of a small volume under limitations imposed by diffusion to and from the reacting
      micro-volume, and consequently restrict ourselves to constant flow. Numerical
      simulation is used to help identify an optimal experimental design. The detection
      of mechanistic changes hinges on linking fluorescence reporters to selected
      reaction components, either directly (chemically) or indirectly (via an indicator
      reaction). We show that rapid mixing experiments are better than chemical
      relaxation experiments, as the statistics of single molecule kinetics affects the
      latter more than the former. However, some fast reaction steps can only be
      revealed by chemical relaxation coupled with mixing experiments. We explore
      connections between our methods and studies of HIV and other systems with RNA to
      DNA transcription.

PMID- 18054368
TI  - Copper speciation in continental inputs to the Vigo Ria: sewage discharges versus
      river fluxes.
AB  - Continental inputs of copper via rivers and sewage into the Vigo Ria were
      evaluated. The main fluvial input is not contaminated and the most degraded
      discharges occur on the southern margin of the middle ria. Continental inputs of
      copper and ligands to the ria are dominated by sewage treatment plants (136 mol
      Cu day(-1), 124 mol L day(-1)) supported by rivers (15 mol Cu day(-1), 21 mol L
      day(-1)). The dissolved fraction is the main channel of discharge for rivers
      (66%) with particulate matter being predominant in sewage (63%). Dissolved copper
      is organically complexed both in rivers (99.8%) and sewage (99.9%). This minor
      difference may be attributed to the fact that the stability of sewage complexes
      is greater than those in rivers. Moreover, ligand concentrations are higher in
      sewage than in rivers. Thus, the natural continental inputs of copper and ligands
      into the ria are magnified by anthropogenic inputs (5-15 and 3-5 times higher for
      copper and ligands, respectively).

PMID- 18054369
TI  - Simultaneous detection and genotyping of porcine reproductive and respiratory
      syndrome virus (PRRSV) by real-time RT-PCR and amplicon melting curve analysis
      using SYBR Green.
AB  - The feasibility of using a SYBR Green-based real-time RT-PCR assay (SYBR Green
      ReTi RT-PCR) followed by melting curve analysis (MCA) for detecting and
      genotyping porcine reproductive and respiratory syndrome virus (PRRSV) was
      assessed. The SYBR Green ReTi RT-PCR and a previously reported two-step, non
      nested RT-PCR assays were simultaneously tested on selected European (EU) and
      North American (US) PRRSV strains and isolates collected from diverse clinical,
      temporal, and geographical origins. The validation experiments showed that the
      optimised SYBR Green ReTi RT-PCR can sensitively and specifically detect PRRSV,
      consistently detecting as little as 0.03TCID(50)/sample of each virus genotype,
      with no type-bias and no amplification signal for other swine pathogens. After
      MCA, two well-differentiated melting temperature (T(m)) profiles for each virus
      genotype were obtained, as sequencing confirmed it. High repeatability was
      obtained for the T(m) values, with intra-run coefficients of variation (CoVs) of
      0.25 and 0.32 and inter-run CoVs of 0.42 and 0.52 for EU and US genotypes,
      respectively. The sensitivity of the SYBR Green ReTi RT-PCR (100%) was higher
      than that of the RT-PCR (95.7%) when testing field isolates. This greater
      sensitivity of the SYBR Green ReTi RT-PCR was further confirmed by the detection
      of a higher proportion of PRRSV-positive diagnostic specimens (29.7%) than by the
      RT-PCR (28.5%). The SYBR Green ReTi RT-PCR test detected infection as early as 2
      dpi in the sera of experimentally infected pigs regardless of virus genotype, and
      discriminated negative (non-inoculated), EU- and US-infected pigs. In conclusion,
      the reported SYBR Green ReTi RT-PCR assay coupled with MCA can detect and type
      PRRSV and may be useful as an alternative diagnostic assay in diverse PRRSV
      epidemiological circumstances.

PMID- 18054370
TI  - A facile and efficient synthesis of some (6E)-hydroximino-4-en-3-one steroids,
      steroidal oximes from Cinachyrella spp. sponges.
AB  - Using beta-sitosterol as a starting material, (6E)-hydroximino-24-ethylcholest-4
      en-3-one (1), a natural steroidal oxime from Cinachyrella alloclada and C. apion,
      was synthesized in four steps with a high overall yield. First, beta-sitosterol
      (5a) is transformed into the corresponding 24-ethylcholest-4-en-3,6-dione (6a)
      via oxidation with pyridinium chlorochromate (PCC). Selective reduction of 6a by
      NaBH(4) in the presence of CoCl(2) gives 24-ethylcholest- 4-en-3beta-ol-6-one
      (7a). The reaction of 7a with hydroxylamine hydrochloride offers the oxime 8a and
      the oxidation of 8a by Jones reagent gives the target steroid 1. (6E)
      Hydroximinocholest-4-en-3-one (2) and (6E)-hydroximino-24-ethylcholest-4,22-dien
      3-one (4) were synthesized by a similar method. The cytotoxicity of the
      synthesized compounds against sk-Hep-1 (human liver carcinoma cell line), H-292
      (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and
      Hey-1B (human ovarian carcinoma cell line) cells were investigated. The presence
      of a cholesterol-type side chain appears to be necessary for the biological
      activity.

PMID- 18054371
TI  - Immunological characterization of a non-toxic peptide conferring protection
      against the toxic fraction (AahG50) of the Androctonus australis hector venom.
AB  - KAaH1 and KAaH2 are non-toxic peptides, isolated from the venom of the
      Androctonus australis hector (Aah) scorpion. In a previous study, we showed these
      peptides to be the most abundant (approximately 10% each) in the toxic fraction
      (AahG50) of the Aah venom. KAaH1 and KAaH2 showed high sequence identities
      (approximately 60%) with birtoxin-like peptides, which likewise are the major
      peptidic components of Parabuthus transvaalicus scorpion venom. Here, we report
      the immunological characterization of KAaH1 and KAaH2. These peptides were found
      to be specifically recognized by polyclonal antibodies raised against AahII, the
      most toxic peptide of Aah venom, and represents the second antigenic group,
      including toxins from different scorpion species in the world. Moreover, KAaH1
      partially inhibits AahII binding to its specific antibody, suggesting some common
      epitopes between these two peptides. The identification of possible key antigenic
      residues in KAaH1 was deduced from comparison of its 3-D model with the
      experimental structure of AahII. Two clusters of putative antigenically important
      residues were found at the exposed surface; one could be constituted of V3 and
      D53, the other of D10, T15 and Y16. Polyclonal antibodies raised against KAaH1 in
      mice were found to cross-react with both AahII and AahG50, and neutralizing
      5LD(50)/ml of the toxic fraction. Mice vaccinated with KAaH1 were protected
      against a challenge of 2LD(50) of AahG50 fraction. All these data suggest that
      KAaH1 has clear advantages over the use of the whole or part of the venom. KAaH1
      is not toxic and could produce sera-neutralizing scorpion toxins, not only from
      Aah venom, but also toxins of other venoms from Buthus, Leiurus, or Parabuthus
      scorpion species presenting antigenically related toxins.

PMID- 18054372
TI  - What does the illusory-flash look like?
AB  - In the illusory-flash effect (Shams, L., Kamitani, Y., & Shimojo, S. (2000).
      Illusions. What you see is what you hear. Nature, 408, 788), one flash presented
      with two tones has a tendency to be seen as two flashes. Previous studies of this
      effect have been ill-equipped to establish whether this illusory-flash is the
      result of a genuine percept, or that of a shift in criterion. We addressed this
      issue by using a stimulus comprising two locations. This enabled contrast
      threshold measurement by means of a location detection task. High-contrast white
      or black flashes were presented simultaneously to both locations, followed by
      threshold contrast flashes of the same contrast polarity at the two locations in
      half of the trials; observers reported whether or not the low-contrast flashes
      had been present. Irrelevant to the task, half of the trials contained one tone,
      the other half contained two tones. In this way, we were able to compute the
      change in sensitivity and shift in criterion between illusory and non-illusory
      trials. We observe both a decrease in visual sensitivity and a criterion shift in
      the illusory-flash conditions. In a second experiment, we were interested in
      determining whether this change in visual sensitivity gave rise to measurable
      visual attributes of the illusory-flash. If it has a contrast, it should interact
      with a spatio-temporally concurrent real flash. Using a similar two-location
      stimulus presentation, we found that under certain conditions, we were able to
      infer the polarity of the perceived illusory-flash. We conclude that the illusory
      flash is indeed a perceptual effect with psychophysically assessable
      characteristics.

PMID- 18054373
TI  - Balance of corneal horizontal coma by internal optics in eyes with intraocular
      artificial lenses: evidence of a passive mechanism.
AB  - It is well known that the aberrations of the cornea are partially compensated by
      the aberrations of the internal optics of the eye (primarily the crystalline
      lens) in young subjects. This effect has been found not only for the spherical
      aberration, but also for horizontal coma. It has been debated whether the
      compensation of horizontal coma is the result of passive mechanism [Artal, P.,
      Benito, A., & Tabernero, J. (2006). The human eye is an example of robust optical
      design. Journal of Vision, 6 (1), 1-7] or through an active developmental
      feedback process [Kelly, J. E., Mihashi, T., & Howland, H. C. (2004).
      Compensation of corneal horizontal/vertical astigmatism, lateral coma, and
      spherical aberration by internal optics of the eye. Journal of Vision, 4 (4), 262
      271]. In this study we investigate the active or passive nature of the horizontal
      coma compensation using eyes with artificial lenses, where no active
      developmental process can be present. We measured total and corneal aberrations,
      and lens tilt and decentration in a group of 38 eyes implanted with two types of
      intraocular lenses designed to compensate the corneal spherical aberration of the
      average population. We found that spherical aberration was compensated by 66%,
      and horizontal coma by 87% on average. The spherical aberration is not
      compensated at an individual level, but horizontal coma is compensated
      individually (coefficients of correlation corneal/internal aberration: -0.946,
      p<0.0001). The fact that corneal (but not total) horizontal coma is highly
      correlated with angle lamda (computed from the shift of the 1st Purkinje image
      from the pupil center, for foveal fixation) indicates that the compensation
      arises primarily from the geometrical configuration of the eye (which generates
      horizontal coma of opposite signs in the cornea and internal optics). The amount
      and direction of tilts and misalignments of the lens are comparable to those
      found in young eyes, and on average tend to compensate (rather than increase)
      horizontal coma. Computer simulations using customized model eyes and different
      designs of intraocular lenses show that, while not all designs produce a
      compensation of horizontal coma, a wide range of aspheric biconvex designs may
      produce comparable compensation to that found in young eyes with crystalline
      lenses, over a relatively large field of view. These findings suggest that the
      lens shape, gradient index or foveal location do not need to be fine-tuned to
      achieve a compensation of horizontal coma. Our results cannot exclude a fine
      tuning for the orientation of the crystalline lens, since cataract surgery seems
      to preserve the position of the capsule.

PMID- 18054374
TI  - Prognostic significance of stathmin expression in correlation with metastasis and
      clinicopathological characteristics in human ovarian carcinoma.
AB  - Stathmin, also called oncoprotein 18, is a founding member of the family of
      microtubule-destabilizing proteins that play a critical role in the regulation of
      mitosis. Stathmin is non-expressed in normal tissues, but stathmin gene is
      expressed at high levels in many human malignancies and the relationships between
      the levels of this gene expression in tumors and prognosis of the patients have
      been addressed. In this report, we explored the relationships between stathmin
      mRNA expression in ovarian carcinoma tissues and clinicopathological parameters.
      We collected and analyzed paraffin wax-embedded ovarian tumor biopsy tissues from
      42 ovarian cancer patients in our hospital. We employed RT-PCR method and
      performed a densitometric analysis to determine the ratio of stathmin relative to
      beta-actin as an internal marker. Results showed that the stathmin mRNA
      expression was detected in all the ovarian carcinoma tissue samples and those
      samples with metastasis had higher levels of stathmin mRNA expression in initial
      biopsy specimens (P<0.05). Moreover, the levels of stathmin mRNA expression
      between samples with and without metastasis showed a statistically significant
      difference (P<0.05).

PMID- 18054375
TI  - Expression of glucagon-like peptide-1 in the taste buds of rat circumvallate
      papillae.
AB  - Glucagon-like peptide-1 (GLP-1), a 30-amino-acid peptide hormone, is a typical
      peptide of the brain-gut axis and can affect the metabolism of various tissues
      and organs. GLP-1 is secreted by intestinal L cells in response to nutrient
      ingestion. Some studies have shown that taste signaling elements were co
      expressed in enteroendocrine cells of the small intestine, and in particular by L
      cells. The present study was performed to explore the protein and mRNA expression
      of GLP-1 in the taste buds of rat circumvallate papillae and to try to determine
      the significance of its secretion. GLP-1 immunoreactivity was observed in spindle
      shaped taste bud cells, with positive cells displaying a characteristic
      distribution of reaction product that was confined to the cytosol. Reverse
      transcription polymerase chain reaction (RT-PCR) assay showed that GLP-1 mRNA was
      expressed in circumvallate papillae. The expression of GLP-1 suggests that it may
      play an important role in the taste stimulation of nutrients and gut hormone
      secretion.

PMID- 18054376
TI  - Significance of tyrosine kinase activity on malign transformation of ovarian
      tumors: a comparison between EGF-R and TGF-alpha.
AB  - Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha)
      are members of the polypeptide growth factor family. The epidermal growth factor
      receptor (EGF-R) is a receptor tyrosine kinase of the ErbB family. Many types of
      cancer, including ovarian cancer, display enhanced EGF-R immunoreactivity on
      their cell surface membranes. Also, an increase in TGF-alpha synthesis and
      secretion usually occurs in human carcinoma cell lines. In this study, we
      compared the immunoreactivities of TGF-alpha and EGF-R in ovarian tumors and
      related immunohistochemical findings to the histological type of the tumors.
      Formalin-fixed, paraffin wax-embedded tissue sections from 40 patients who had
      serous-mucinous borderline tumor and serous-mucinous adenocarcinoma of the ovary
      (n=10 each) were stained with hematoxylin-eosin and labeled for binding of
      primary antibodies against TGF-alpha and EGF-R using an avidin-biotin-peroxidase
      method. A semi-quantitative grading system was used to compare
      immunohistochemical labeling intensities. Increased immunoreactivity of EGF-R and
      moderate immunoreactivity of TGF-alpha was detected in adenocarcinomas. There was
      no significant difference in the immunoreactivity of TGF-alpha among the
      histologic types of ovarian tumors. The results of this study support the
      hypothesis that EGF-R may be a more useful marker than TGF-alpha in epithelial
      ovarian tumors.

PMID- 18054377
TI  - A genome-wide inventory of neurohormone GPCRs in the red flour beetle Tribolium
      castaneum.
AB  - Insect neurohormones (biogenic amines, neuropeptides, and protein hormones) and
      their G protein-coupled receptors (GPCRs) play a central role in the control of
      behavior, reproduction, development, feeding and many other physiological
      processes. The recent completion of several insect genome projects has enabled us
      to obtain a complete inventory of neurohormone GPCRs in these insects and, by a
      comparative genomics approach, to analyze the evolution of these proteins. The
      red flour beetle Tribolium castaneum is the latest addition to the list of
      insects with a sequenced genome and the first coleopteran (beetle) to be
      sequenced. Coleoptera is the largest insect order and about 30% of all animal
      species living on earth are coleopterans. Some coleopterans are severe
      agricultural pests, which is also true for T. castaneum, a global pest for stored
      grain and other dried commodities for human consumption. In addition, T.
      castaneum is a model for insect development. Here, we have investigated the
      presence of neurohormone GPCRs in Tribolium and compared them with those from the
      fruit fly Drosophila melanogaster (Diptera) and the honey bee Apis mellifera
      (Hymenoptera). We found 20 biogenic amine GPCRs in Tribolium (21 in Drosophila;
      19 in the honey bee), 48 neuropeptide GPCRs (45 in Drosophila; 35 in the honey
      bee), and 4 protein hormone GPCRs (4 in Drosophila; 2 in the honey bee).
      Furthermore, we identified the likely ligands for 45 of these 72 Tribolium GPCRs.
      A highly interesting finding in Tribolium was the occurrence of a vasopressin
      GPCR and a vasopressin peptide. So far, the vasopressin/GPCR couple has not been
      detected in any other insect with a sequenced genome (D. melanogaster and six
      other Drosophila species, Anopheles gambiae, Aedes aegypti, Bombyx mori, and A.
      mellifera). Tribolium lives in very dry environments. Vasopressin in mammals is
      the major neurohormone steering water reabsorption in the kidneys. Its presence
      in Tribolium, therefore, might be related to the animal's need to effectively
      control water reabsorption. Other striking differences between Tribolium and the
      other two insects are the absence of the allatostatin-A, kinin, and corazonin
      neuropeptide/receptor couples and the duplications of other hormonal systems. Our
      survey of 340 million years of insect neurohormone GPCR evolution shows that
      neuropeptide/receptor couples can easily duplicate or disappear during insect
      evolution. It also shows that Drosophila is not a good representative of all
      insects, because several of the hormonal systems that we now find in Tribolium do
      not exist in Drosophila.

PMID- 18054378
TI  - Reproductive performance of dairy cows with ovarian cysts after synchronizing
      ovulation using GnRH or hCG during the warm or cool period of the year.
AB  - This study was designed to compare the reproductive response to timed AI of
      lactating dairy cows with cystic ovarian follicles treated with GnRH or hCG to
      synchronize ovulation. The effectiveness of treatment during the warm or cool
      period of the year was also compared. Cows were given 12 microg GnRH-agonist i.m.
      on day 0 of the protocol, 15 mg PGF(2alpha) i.m. on day 7, and either GnRH
      agonist (GPG treatment) or 3000 IU hCG i.m. (GPH treatment) on day 9, followed by
      timed AI. The cows were randomly chronologically assigned to GPG (n=130) or GPH
      (n=136) group. All cows were inseminated at fixed time 16-22 h after the end of
      treatment. During the warm period the pregnancy rate to first AI was 12% (7/60)
      and 21% (14/68) for the GPG and GPH groups, respectively, there being no
      significant differences between groups; the cumulative pregnancy rate was 22%
      (13/60) and 21% (14/68) for the GPG and GPH groups, respectively, again with no
      significant intergroup differences. During the cool period pregnancy rate to
      first AI was not different between groups: 29% (20/70) for GPG and 32% (22/68)
      for GPH, respectively; whereas the cumulative pregnancy rate was significantly
      higher (P<0.05) for the GPH groups than for the GPG group: 56% (39/70) and 78%
      (53/68), respectively. These findings indicate that during the warm period, the
      pregnancy rates of the cystic cows were similar whether they received GPG or GPH
      treatment, during the cool period, there is a beneficial effect to use hCG at day
      9 of the ovsynch protocol compared GnRH on cumulative pregnancy rate.

PMID- 18054379
TI  - Task related modulation of the motor system during language processing.
AB  - Recent neurophysiological and brain imaging studies have shown that the motor
      system is involved in language processing. However, it is an open question
      whether this involvement is a necessary requisite to understand language or
      rather a side effect of distinct cognitive processes underlying it. In order to
      clarify this issue we carried out three behavioral experiments, using a go-no go
      paradigm. Italian verbs expressing hand actions, foot actions or an abstract
      content served as stimuli. Participants used their right hands to respond. In
      Experiment 1, in which a semantics decision task with an early delivery of the go
      signal (during processing language material) was used, slower responses were
      found for hand action-related verbs than for foot action-related verbs. In
      Experiment 2, using the same task with either an early or a delayed delivery of
      the go signal (when language material had been already processed), no difference
      was found between responses to the two verb categories in the delayed delivery
      condition. In Experiment 3, in which a lexical decision task with an early
      delivery of the go signal was used, again no difference between the two verb
      categories was found. The present findings demonstrate that during language
      processing the modulation of the motor system crucially occurs while performing a
      semantics decision task, thus supporting the notion that this involvement is a
      necessary step to understand language rather than a side effect of upstream
      cognitive processes.

PMID- 18054380
TI  - Comparative study on torsional strength, ductility and fracture characteristics
      of laser-welded alpha+beta Ti-6Al-7Nb alloy, CP Titanium and Co-Cr alloy dental
      castings.
AB  - OBJECTIVES: The purpose of this study was to compare torsional strength,
      ductility and fracture behaviors of Ti-6Al-7Nb, CP Ti and Co-Cr alloy castings
      after laser welding. METHODS: Dumbbell-shaped castings of three metal alloys (Ti
      6Al-7Nb alloy, CP Ti, Co-Cr alloy) were cut in half and laser welded with a
      Nd:YAG pulse laser-welding machine at either 220V or 260V of laser voltage. After
      being laser welded, all cast specimens were tested with a multi-axial hydraulic
      testing machine (MTS 858 Mini Bionix) using a torsional test. The fracture
      surfaces were investigated with a scanning electron microscope. RESULTS: None of
      the laser-welded Ti-6Al-7Nb alloy and CP Ti castings was broken within the welded
      joint, showing torsional strength as high as the unwelded castings. Unlike the
      other groups, the laser-welded Co-Cr alloy castings exhibited brittle fracture
      appearance and provided substantially less torsional strength. SIGNIFICANCE: The
      torsional strength of the laser-welded Ti-6Al-7Nb alloy and CP Ti castings was as
      high as that of the unwelded castings while this finding could not apply to the
      Co-Cr alloy castings. This indicates that the mechanical strength of the laser
      welded Ti-6Al-7Nb alloy dental casting is sufficient for clinical applications.

PMID- 18054381
TI  - Spray-dried chitosan microspheres containing 8-hydroxyquinoline -5 sulphonic acid
      as a new adsorbent for Cd(II) and Zn(II) ions.
AB  - In the present study, a new chelating adsorbent was prepared from chitosan
      microspheres cross-linked with glutaraldehyde by spray drying using 8
      hydroxyquinoline -5 sulphonic acid as chelant agent (CTS-SX-CL). Microspheres of
      the new adsorbent were characterized by Raman spectroscopy, scanning electron
      microscopy (SEM) and energy-dispersive X-ray microanalysis (EDX). The effect of
      pH, contact time and concentration of metallic ions in solution were evaluated on
      the adsorption behavior of Cd(II) and Zn(II) by CTS-SX-CL. Adsorption was maximum
      for both Cd(II) and Zn(II) at pH 8.0. Adsorption kinetic curves were obtained and
      could be fit by the pseudo second-order adsorption model. An analysis of
      equilibrium adsorption data using the Langmuir isotherm model indicated that the
      maximum adsorption capacity of CTS-SX-CL was higher than that of CTS-CL for both
      ions investigated. The adsorption capacity increased 74% for Cd(II).

PMID- 18054382
TI  - Characterization of a fucoidan from Lessonia vadosa (Phaeophyta) and its
      anticoagulant and elicitor properties.
AB  - Blades of Lessonia vadosa (Phaeophyta) were extracted with 2% CaCl(2) solution,
      affording in 4.4% yield a polysaccharide which contained fucose and sulfate
      groups in the molar ratio 1.0:1.12. The high negative optical activity value
      ([alpha](D)(22)=-134.0 degrees ), FT-IR and NMR analysis suggest the presence of
      a fucoidan. (13)C NMR spectrum of the polysaccharide obtained by solvolytic
      desulfation of native fucoidan indicated the major presence of 1-->3 linked alpha
      l-fucan. Depolymerization of the native fucoidan with H(2)O(2) in the presence of
      copper(II) acetate gave in 54.8% yield a fraction with 33.7% of sulfate content.
      The native fucoidan (MW 320,000) showed good anticoagulant activity whereas the
      radical depolymerized fraction (MW 32,000) presented a weak anticoagulant
      activity. These polysaccharides showed significant activation of phenylalanine
      ammonia lyase (PAL), lipooxygenase (LOX) and glutathione-S-transferase (GST)
      defence enzyme activities in tobacco plants.

PMID- 18054383
TI  - Structural changes in umbilical vessels in pregnancy induced hypertension.
AB  - BACKGROUND: Pregnancy Induced Hypertension (PIH) is associated with placental
      morphological changes, alterations in the blood flow patterns in the umbilical
      vessels and adverse fetal and maternal outcome. Studies have demonstrated changes
      in the structure of the umbilical vessels but these have not been described
      across the length of the cord or correlated with the severity of disease. STUDY
      DESIGN: A case control study. SETTING: Kenyatta National Hospital. MATERIALS AND
      METHODS: Thirty six umbilical cords from newborns of women with and without PIH
      (18 cases, 18 controls) were obtained and studied with light microscopy. Of the
      cases 9 women had severe PIH and 9 had mild PIH. Means and standard deviations
      for the various parameters of the various groups were obtained. Student's t-test
      and ANOVA were used to compare means, a p value of <0.05 being significant.
      RESULTS: The structure of the umbilical vessels changes from the placental end to
      the fetal end. The umbilical vein in PIH had a greater wall thickness and a
      smaller luminal area than in the controls. The vein's wall-luminal ratio
      increased from the placental to the fetal end. Duplication of the elastic
      subintimal lamina (ESL) was higher in the cases. The ESL was more commonly
      duplicated in the fetal end. There were no structural differences between the
      umbilical arteries in PIH and in the controls. CONCLUSION: PIH is associated with
      structural changes in the umbilical vessels. These changes are more predominant
      in the vein than in the artery and in the vein, they are more obvious in the
      fetal end. The observed increase in wall-luminal ratio from the placental to the
      fetal end suggests that the fetal end of the umbilical vein has a more refined
      role in the regulation of blood flow to the fetus.

PMID- 18054385
TI  - Physiological and biochemical effects of allelochemical ethyl 2-methyl
      acetoacetate (EMA) on cyanobacterium Microcystis aeruginosa.
AB  - The physiological and biochemical effects of an allelochemical ethyl 2-methyl
      acetoacetate (EMA) isolated from reed (Phragmites communis) on bloom-forming
      cyanobacterium, Microcystis aeruginosa, were investigated. EMA significantly
      inhibited the growth of M. aeruginosa in a concentration-dependent way. The
      metabolic indices (represented by esterase and total dehydrogenase activities),
      the cellular redox status (represented by the level of reactive oxygen species
      (ROS)), and the oxidative damage index (represented by the content of
      malondialdehyde (MDA), the product of membrane lipid peroxidation) were used to
      evaluate the physiological and biochemical changes in M. aeruginosa after EMA
      exposure. Esterase activity in M. aeruginosa did not change (P>0.05) after 2 h of
      exposure to EMA, but increased greatly after 24 and 48 h (P<0.05). EMA exposure
      (>0.5 mg L(-1)) resulted in a remarkable loss of total dehydrogenase activity in
      M. aeruginosa after 4 h (P<0.01), but an increase after 40 h (P<0.05). EMA caused
      a great increase in ROS level of the algal cells. At high EMA concentration (4 mg
      L(-1)), the ROS level was remarkably elevated to 1.91 times as much as that in
      the controls after 2 h. Increases in the ROS level also occurred after 24 and 48
      h. The increase in lipid peroxidation of M. aeruginosa was dependent upon EMA
      concentration and the exposure time. After 40 h of exposure, the MDA content at 4
      mg L(-1) of EMA reached approximately 3.5 times (P<0.01) versus the controls.
      These results suggest that the cellular structure and metabolic activity of M.
      aeruginosa are influenced by EMA; the increased metabolic activity perhaps
      reflects the fact that the resistance of cellular response system to the stress
      from EMA is initiated during EMA exposure, and the oxidative damage induced by
      EMA via the oxidation of ROS may be an important factor responsible for the
      inhibition of EMA on the growth of M. aeruginosa.

PMID- 18054384
TI  - Human embryonic stem cells as models for trophoblast differentiation.
AB  - Trophectoderm is specified from pluripotent blastomeres at some time prior to
      blastocyst formation. Proliferating cytotrophoblast derived from trophectoderm is
      the forerunner of the entire trophoblast component of the mature human placenta,
      including extravillous cytotrophoblast and syncytiotrophoblast. Recently human
      embryonic stem cells (hESC) have been employed to study these events in an in
      vitro situation. Here we review some of the work in this emerging area of
      trophoblast biology. We concentrate primarily on a model in which colonies of
      hESC are exposed to BMP4 in stem cell growth medium lacking FGF2. Under both low
      (4%) and high (20%) O(2) conditions, differentiation proceeds unidirectionally
      towards trophoblast from the outside of the colonies inwards, with the
      progression fastest under high O(2). Immunohistochemical observations performed
      on whole colonies combined with microarray analysis of mRNA can be employed to
      track developmental transitions as they occur over time and in two-dimensional
      space as the cells respond to BMP4.

PMID- 18054386
TI  - Studies on the haemolytic activity of circulating C1q-C3/C4 complexes.
AB  - During classical complement pathway activation, the internal thio-ester of both
      C3 and C4 becomes exposed which enables C3 and C4 to bind covalently to nearby
      molecules. Recently, we described that C3 and C4 bind to C1q, the recognition
      molecule of the classical pathway, upon activation of this pathway. Covalently
      linked complexes between C1q and activated C4 (C1q-C4 complexes) are specific
      markers for classical complement pathway activation. In the present study we
      further investigated the molecular characteristics of complexes between C1q and
      activated C3 or C4 that occur in vivo. In human serum only complexes of C1q with
      C3d or C4d fragments were detected but not those with the larger C3b/bi or C4b/bi
      fragments. We identified that C1q-C4 complexes circulate as part of the intact C1
      complex instead of as free C1q. Finally, we investigated whether deposited C3d or
      C4d affect C1 haemolytic activity. We observed that both C1q-C3 and C1q-C4
      complexes are significantly (P<0.05) less active in a C1q-haemolytic assay than
      non-complexed C1q. Thus, the dominant types of C1q complexes that circulate in
      vivo are C1q-C3d and C1q-C4d complexes. These complexes are still able to
      interact with C1r and C1s to form a C1 complex, but seem to have a reduced
      activity as compared to C1q not carrying C3- or C4-fragments.

PMID- 18054387
TI  - Short peptide sequences mimic HLA-DM functions.
AB  - HLA-DM (DM) plays a critical role in Ag presentation to CD4 T cells by catalyzing
      the exchange of peptides bound to MHC class II molecules. It is known that DM
      interaction with MHC II involves conformational changes in the MHC II molecule
      leading to the disturbance of H-bonds formed between the bound peptide and the
      MHC II groove leading to peptide dissociation. The specific region of the DM
      molecule that induces this peptide dissociation is not defined. In this study, we
      describe three short peptides (helper peptides) that accelerate DM-catalyzed
      peptide exchange. Kinetic studies presented here demonstrate that these peptides
      act similarly to DM in; (a) enhancing peptide binding to HLA-DR1; (b)
      dissociation of complexes of peptide-DR1; and (c) maintaining a receptive
      conformation of empty DR1. We further report that helper peptides are effective
      in increasing peptide binding to DR1 expressed on B cells in vitro, and, when
      mixed with peptide and adjuvant, cause enhanced T cell priming in HLA-DR1 Tg
      mice. We suggest that helper peptides might interact with the same critical
      residues on MHC class II that is targeted by DM.

PMID- 18054388
TI  - The immunogenic CBD1 peptide corresponding to the caveolin-1 binding domain in
      HIV-1 envelope gp41 has the capacity to penetrate the cell membrane and bind
      caveolin-1.
AB  - The potential caveolin-1 binding domain (CBD), referred to as CBD1 and CBD2, is
      highly conserved in the transmembrane envelope glycoprotein of various HIV-1 and
      HIV-2 isolates, respectively. However, HIV-1 neutralizing antibodies raised
      against the synthetic CBD1 peptide (SLEQIWNNMTWMQWDK) do not cross-react with the
      CBD2 peptide (SLTPDWNNMTWQEWER) and have no effect on HIV-2 infection. Here we
      show that the CBD2 peptide is not immunogenic under similar immunization
      conditions as the CBD1 peptide. Moreover, the CBD1 but not the CBD2 peptide has
      the capacity to bind caveolin-1 in crude cell extracts thus suggesting the
      existence of structural and/or conformational differences between CBD1 and CBD2.
      Accordingly, circular dichroism spectroscopy and fluorimetry analysis indicated
      that CBD1 but not CBD2 could adopt a defined secondary structure and form a
      complex with a peptide corresponding to the caveolin-1 scaffolding domain, which
      is the site of interaction of caveolin-1 with various proteins. In line with
      these observations, CBD1 but not CBD2 binds cells and forms large aggregates at
      the plasma membrane by colocalizing with cytofacial caveolin-1. This latter is
      dependent on the lipid raft integrity of the plasma membrane. Supporting that the
      ability to penetrate into plasma membranes is sustained by folding at the
      interface, CBD1 but not CBD2 has the capacity to insert into lipid monolayers,
      penetrate into artificial membranes and adopt a beta-sheet conformation in
      presence of lipid vesicles. These structural determinants and membrane
      partitioning properties could account for the immunogenicity of the CBD1 peptide
      in various animals.

PMID- 18054389
TI  - PBDE-47-induced oxidative stress, DNA damage and apoptosis in primary cultured
      rat hippocampal neurons.
AB  - 2,2',4,4'-Tetrabromodiphenyl ether (PBDE-47) causes developmental neurotoxicity
      in animal studies, but the mechanism remains poorly understood. This paper
      investigates the mechanism by studying the effects of oxidative stress, DNA
      damage, and apoptosis induced by PBDE-47 in cultured primary rat hippocampal
      neurons at different PBDE-47-concentrations (0, 2.06, 20.6, and 41.2 microM). The
      results showed that reactive oxygen species (ROS) level, percentage of apoptosis,
      malondialdehyde (MDA) content, the glutathione peroxidase (GSH-Px) level and the
      lactic dehydrogenase (LDH) leakage rate were affected by exposure of cells to
      41.2 microM PDBE-47 (P<0.05), but not to the lower concentrations tested (20.6
      and 2.06 microM). Reduced glutathione (GSH), superoxide dismutase (SOD), and
      increased DNA damage (tested by a comet assay) were affected at all
      concentrations tested in a dose-related manner (P<0.05). These results suggested
      that PBDE-47 could induce oxidative stress, DNA damage, and apoptosis in primary
      rat hippocampal neurons. Whether or not this concentration response pattern
      indicates that ROS leads to DNA damage and/or apoptosis must be confirmed with
      further experiments.

PMID- 18054390
TI  - Monoclonal antibodies to equine IgM improve the sensitivity of West Nile virus
      specific IgM detection in horses.
AB  - West Nile virus (WNV) is a zoonotic pathogen of global importance. In horses with
      neurological signs, detection of WNV-specific immunoglobulin M (IgM) in serum is
      widely used to identify clinical cases of WNV encephalitis. Here, we describe the
      development of two monoclonal antibodies (mAbs) to equine IgM which were used in
      a WNV IgM-specific enzyme-linked immunosorbent assay (ELISA). Their performance
      was compared to an established assay based on polyclonal anti-IgM. Check test
      serum samples from the National Veterinary Service Laboratory (NVSL) were used to
      evaluate the performance of the three anti-IgM antibodies. The anti-IgM 1-22 mAb
      correctly identified all NVSL samples. Both the polyclonal antibody and
      monoclonal anti-IgM 2B-63 identified eight out of ten samples correctly. The
      three assays were then compared using serum samples from clinically healthy
      animals (n=33) and horses with neurological signs (n=21). High Spearman rank
      correlations (0.76-0.86) were found among the ELISA results. Inter-test
      agreements (weighted kappa) for assay interpretation resulted in strong agreement
      (0.95) of the results obtained by the mAbs and moderate agreements when
      monoclonal and polyclonal anti-IgM-based assays were compared. To determine the
      analytical sensitivities of anti-WNV IgM detection, serial dilutions of WNV IgM
      positive serum samples were analyzed. The highest sensitivity was obtained by
      using the anti-IgM 1-22 mAb to capture IgM from equine serum. In conclusion, the
      use of monoclonal anti-IgM antibodies can improve the sensitivity of IgM
      detection in the acute phase of WN disease.

PMID- 18054391
TI  - PI3 kinase and direct S-nitrosation are involved in down-regulation of apoptosis
      signal-regulating kinase 1 during LPS-induced Toll-like receptor 4 signalling.
AB  - Toll-like receptor 4 (TLR4) is the human pattern recognition receptor that
      detects lipopolysaccharide (LPS) shared by Gram-negative bacteria. TLR4 is
      expressed in different cell types including myeloid cells, the key effectors of
      innate immune reactions. Apoptosis signal-regulating kinase 1 (ASK1), the
      upstream kinase of MAP kinase-dependent apoptotic pathway has recently been found
      to be selectively required for p38 MAP kinase activation/cytokine production
      during TLR4 signalling. However, the activity of this enzyme has to be down
      regulated to protect the cells against apoptosis. In the present study we have
      found that inhibition of PI3 kinase by LY294002 in THP-1 cells exposed to LPS
      attenuated down-regulation of ASK1 activity followed by programmed cell death. In
      addition, nitric oxide produced in response to exposure of THP-1 cells to LPS was
      found to S-nitrosate and therefore, down-regulate ASK1 activity.

PMID- 18054392
TI  - Intralesional steroid injection for proliferative parotid hemangiomas.
AB  - OBJECTIVE: To evaluate the efficacy of proliferative phase intralesional steroid
      injections in the treatment of parotid hemangiomas. DESIGN: Retrospective
      analysis of pediatric patients with parotid hemangiomas treated with
      intralesional steroid injections during the proliferative phase. SETTING:
      Vascular Anomalies Center, University of Arkansas for Medical Sciences, Arkansas
      Children's Hospital, Little Rock, Arkansas, USA. PATIENTS: Twenty-one pediatric
      patients, ages 4-39 months. METHODS: Between 2001 and 2006, 21 patients received
      steroid injections for 23 parotid hemangiomas (bilateral in 2 patients). A total
      of 1-3 injections over the first year of life were given at 6-25 week intervals.
      RESULTS: Main outcome measures included softening, decreased growth rate, and/or
      decrease in size. After injection, achievement of outcome measures occurred with
      all lesions. No incidence of tissue atrophy or facial nerve injury was seen. Four
      of 21 (19%) patients developed failure to thrive (FTT). CONCLUSION: Parotid
      hemangiomas can be effectively controlled with proliferative phase intralesional
      steroid injections. Injections may limit the need for future extensive surgery.
      Further prospective randomized trials are needed to support these claims. Failure
      to thrive may be a potential complication of intralesional steroid injection.
      Endocrine/growth monitoring should be considered when treating with intralesional
      steroids.

PMID- 18054393
TI  - A rapid method for gene expression analysis of Borna disease virus in neurons and
      astrocytes using laser microdissection and real-time RT-PCR.
AB  - Laser microdissection combined with real-time RT-PCR represents a powerful method
      to analyse the transcription efficiency of defined cell types. Therefore, a RNA
      preserving immunolabelling method was established to identify neurons and
      astrocytes in persistently BDV-infected rat brain sections for subsequent laser
      microdissection and quantitation of viral gene products by real-time RT-PCR.
      Firstly, to ensure an accurate measurement of viral RNA after immunolabelling,
      different reference genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH],
      succinate-ubiquinone reductase [SDHA], hypoxanthine phosphoribosyl-transferase-1
      [HPRT]) were tested. Only normalisation with GAPDH yielded a stable relative
      expression of viral RNA encoding the nucleoprotein (BDV-N), the matrixprotein and
      the glycoprotein (intron I and intron II). The two remaining reference genes
      biased the ratios of BDV-transcripts in the immunolabelled brain sections
      significantly. Secondly, 100 immunolabelled neurons and astrocytes were harvested
      using laser microdissection and amplification of all viral transcripts revealed
      681 and 168 (BDV-N), 573 and 254 (intron I), 324 and 133 (intron II) and 161 and
      36 (GAPDH) absolute copy numbers in neurons and astrocytes, respectively. Thus,
      laser microdissection combined with real-time RT-PCR provides an effective tool
      for the analysis of cell-specific viral transcription efficiency and allows
      elucidating virus-host-interactions and virus persistence mechanisms in the CNS.

PMID- 18054394
TI  - Posttranscriptional control of neuronal development by microRNA networks.
AB  - The proper development of the nervous system requires precise spatial and
      temporal control of gene expression at both the transcriptional and translational
      levels. In different experimental model systems, microRNAs (miRNAs) - a class of
      small, endogenous, noncoding RNAs that control the translation and stability of
      many mRNAs - are emerging as important regulators of various aspects of neuronal
      development. Further dissection of the in vivo physiological functions of
      individual miRNAs promises to offer novel mechanistic insights into the gene
      regulatory networks that ensure the precise assembly of a functional nervous
      system.

PMID- 18054395
TI  - Treatment of Argentine hemorrhagic fever.
AB  - Argentine hemorrhagic fever (AHF) is a rodent-borne illness caused by the
      arenavirus Junin that is endemic to the humid pampas of Argentina. AHF has had
      significant morbidity since its emergence in the 1950s, with a case-fatality rate
      of the illness without treatment between 15% and 30%. The use of a live
      attenuated vaccine has markedly reduced the incidence of AHF. Present specific
      therapy involves the transfusion of immune plasma in defined doses of
      neutralizing antibodies during the prodromal phase of illness. However,
      alternative forms of treatment are called for due to current difficulties in
      early detection of AHF, related to its decrease in incidence, troubles in
      maintaining adequate stocks of immune plasma, and the absence of effective
      therapies for severely ill patients that progress to a neurologic-hemorrhagic
      phase. Ribavirin might be a substitute for immune plasma, provided that the
      supply is guaranteed. Immune immunoglobulin or monoclonal antibodies should also
      be considered. New therapeutic options such as those being developed for systemic
      inflammatory syndromes should also be valuated in severe forms of AHF.

PMID- 18054396
TI  - Lateral habenula lesions improve the behavioral response in depressed rats via
      increasing the serotonin level in dorsal raphe nucleus.
AB  - The dorsal raphe nucleus (DRN)-serotonin (5-HT) system plays a key role in stress
      related psychiatric disorders such as anxiety and depression. The habenular
      nucleus (Hb) is closely connected with the DRN both morphologically and
      functionally. Here, we used two types of depressive animal models by exposing
      rats to chronic mild stress (CMS) and by chronically administering the tricyclic
      antidepressant clomipramine (CLI) in the rat during the neonatal state of life to
      produce adult depressed rats. We investigated the effects of lateral habenular
      nucleus (LHb) lesions on the behavioral response and on the level of 5-HT in DRN
      in the depressed rats. Forced-swimming test (FST) showed that the immobility time
      decreased, and the climbing time increased after lesioning LHb of depressed rats.
      Microdialysis results indicated that the 5-HT level in DRN in depressed rats was
      lower than that of the control group. Lesion of the LHb was followed by an
      increased 5-HT turnover in the DRN. Our results suggested that the lesion of the
      LHb could improve the behavioral response of the depressed rats and the 5-HT
      level of the DRN increased by LHb lesions could be involved in the effects.

PMID- 18054397
TI  - Different patterns of freezing behavior organized in the periaqueductal gray of
      rats: association with different types of anxiety.
AB  - Freezing defined as the complete absence of body movements is a normal response
      of animals to unavoidable fear stimuli. The present review presents a series of
      evidence relating different defensive patterns with specific anxiety disorders.
      There are at least four different kinds of freezing with specific neural
      substrates. The immobility induced by stimulation of the ventral column of the
      periaqueductal gray (vPAG) has been considered a quiescence characteristic of the
      recovery component of defense-recuperative processes. There is an isomorphism
      between freezing response to contextual stimuli paired with electrical shocks and
      generalized anxiety disorder. Besides, two types of freezing emerge with the
      electrical stimulation of the dorsal aspects of the periaqueductal gray (dPAG):
      the dPAG-evoked freezing and the dPAG post-stimulation freezing. Evidence is
      presented in support of the hypothesis that whereas dPAG-evoked freezing would
      serve as a model of panic attacks, the dPAG post-stimulation freezing appears to
      be a model of panic disorder. It is also proposed that conditioned freezing plus
      dPAG electrical stimulation might also mimic panic disorder with agoraphobia. A
      model of serotoninergic modulation through on- and off-cells of the defense
      reaction generated in the dPAG is also presented. The understanding of how the
      periaqueductal gray generates and elaborates different types of freezing is of
      relevance for our better knowledge of distinct types of anxiety such as panic
      disorder or generalized anxiety disorder.

PMID- 18054398
TI  - Gene expression profiling reveals upregulation of Tlr4 receptors in Cckb receptor
      deficient mice.
AB  - The cholecystokinin B (2) receptor knockout (Cckbr KO) protects against allodynia
      induced by chronic constriction injury (CCI). The mechanism of this phenomenon is
      unknown, but must involve persistent changes in pain modulation and/or
      inflammatory pathways. We performed a gene expression study in two brain areas
      (midbrain and medulla) after surgical induction of CCI in Cckbr KO and wild-type
      (wt) control mice. The patterns of gene expression differences suggest that the
      immune system is activated in higher brain structures following CCI in the wt
      mice. The strongest differences include genes related to the MAPK pathway
      activation and cytokine production. In Cckbr KO mice this expressional pattern
      was absent. In addition, we found significant elevation of the Toll-like receptor
      4 (Tlr4) in the supraspinal structures of the mice with deleted Cckbr compared to
      wt control mice. This up-regulation is most likely induced by the deletion of
      Cckbr. We suggest that there is a functional deficiency in the Tlr4 pathway which
      disables the development of neuropathic pain in Cckbr KO mice. Indeed, real time
      PCR analysis detected a CCI-induced upregulation of Tlr4 and Il1b expression in
      the lumbar region of wt but not Cckbr KO mice. Gene expression profiling
      indicates that elements of the immune response are not activated in Cckbr KO mice
      following CCI. Our findings suggest that there may be a role for CCK in the
      regulation of innate immunity.

PMID- 18054399
TI  - Activation differences in observation of hand movements for imitation or velocity
      judgement.
AB  - We aimed to investigate the brain areas engaged in observation of hand movements
      with the intention of imitation or judging movement velocity. Both processes
      reflect different analytic approaches in movement observation. We were interested
      if these two processes can be distinguished or share common activation foci.
      Twelve healthy, right-handed volunteers were required to observe video clips of
      hand gestures and of object related grasping movements while the regional
      cerebral blood flow was measured using positron emission tomography. The subjects
      were instructed either to imitate the actions or to judge the velocity of the
      observed movements after scanning. Action observation with the instruction to
      judge movement velocity engaged bilaterally the temporo-occipital junction and
      adjacent visual cortical areas. In contrast, observation with the instruction to
      imitate them afterwards, yielded large activation clusters covering the left
      parietal and premotor cortex. Both contrasts demonstrated activation in the
      inferior frontal cortex, however, on opposite sides. Results suggest that
      movement observation with the goal of imitation activated specific areas of the
      parietal cortex in the dominant hemisphere probably related to programming of the
      movement kinematics. In contrast, observation with the goal to characterize the
      velocity of the finger movements activated the ventral visual pathways. Thus,
      movement observation recruits non-overlapping cortical networks, depending on the
      information attended to which are characterised by a dorsal ventral dissociation.

PMID- 18054400
TI  - Intra hippocampal injection of testosterone impaired acquisition, consolidation
      and retrieval of inhibitory avoidance learning and memory in adult male rats.
AB  - The hippocampus is essentially involved in learning and memory, and is known to
      be a target for androgen actions. Androgen receptors are densely expressed in CA1
      of rat hippocampus, and mediate the effects of testosterone (T) on learning and
      memory. T depletion or administration can modulate neural function and cognitive
      performance. We conducted series of experiments to further investigate the effect
      of castration or intra hippocampal injection of T on acquisition, consolidation
      and retrieval of inhibitory avoidance learning and memory. Male adult rats were
      bilaterally cannulated into CA1 of hippocampus, and then received T (1, 10, 20,
      40 and 80mug/0.5mul/side) or vehicle (DMSO), 30min before training, immediately
      after training and 30min before retrieval in inhibitory avoidance task.
      Castration was made by gonadectomy of male rats and behavioral tests performed 4
      weeks later. Our results showed that gonadectomy of male rats did not influence
      performance on inhibitory avoidance task, as compared to sham-operated rats. We
      have also found that pre-training, post-training and pre-retrieval intra CA1
      injections of T significantly decreased step-through latencies in inhibitory
      avoidance learning at doses 1 and 80, 20, and 20 and 40mug/0.5mul/side,
      respectively. The data suggest that intra CA1 administration of T could impair
      learning and memory acquisition, consolidation and retrieval, while systemic
      androgen's depletion have no effect on memory, in inhibitory avoidance task.

PMID- 18054401
TI  - Role of age and gender in the perception of aging: a community-based survey in
      Kuwait.
AB  - It was aimed at investigating the perception of the aging process by the adult
      population in Kuwait and the existence of gender-dependent ageism. A total of 305
      adults aged between 20 and 64 years were selected among those attending health
      centers in Kuwait. They were interviewed using a pre-tested questionnaire and
      data was collected through direct one-to-one interview using the incidental
      sampling method. Over 74% of both group of respondents considered age as a
      defining factor for elderly women, however, only 62.2% of women and 67% of men
      thought age defined elderly men. Body image was an important criterion and a
      significant association between age of the respondents with body image and mental
      alertness in defining elderly women was observed (p<0.001). Only 1.6% agreed that
      the elderly required geriatric homes, 69.9% agreed they feared death and up to
      78.8% of the respondents agreed that the elderly were irritable. Some degree of
      gender ageism was evident in both groups of respondents. In general, though
      Kuwait has undergone extensive socio-cultural changes associated with
      modernization, the status of the elderly as an indispensable part of the family
      continues to remain.

PMID- 18054402
TI  - Effects of substance P on neuronal firing of pallidal neurons in parkinsonian
      rats.
AB  - Substance P is an important neurotransmitter or neuromodulator in central nervous
      system. Morphological studies have revealed the existence of substance P and its
      high affinity receptor, neurokinin-1 receptor, in globus pallidus. The expression
      of neurokinin-1 receptor in external globus pallidus has been reported to be
      decreased or unchanged in parkinsonian patients. To further investigate the
      effects of pallidal neurokinin-1 receptor in Parkinson's disease, an in vivo
      extracellular recording in 6-hydroxydopamine parkinsonian rats was performed.
      Micro-pressure ejection of selective neurokinin-1 receptor agonist,
      [Sar9,Met(O2)11] substance P (0.1mM), increased the spontaneous firing rate of
      pallidal neurons by 9.1% on the lesioned side, which was significantly weaker
      than that on the unlesioned side (20.7%), and that in normal rats (30.0%). The
      selective neurokinin-1 receptor antagonist, SR140333B, prevented the excitatory
      effects induced by [Sar9,Met(O2)11] substance P. Based on the action of substance
      P in globus pallidus of parkinsonian rats we hypothesize that the activity of
      neurokinin-1 receptors in globus pallidus may be decreased under parkinsonian
      state. This finding may provide a rationale for further investigations into the
      potential of pallidal substance P system in the treatment of Parkinson's disease.

PMID- 18054403
TI  - Oxidation of peptides and proteins by Trichoderma reesei and Agaricus bisporus
      tyrosinases.
AB  - The capability of a novel tyrosinase from Trichoderma reesei (TrTyr) to catalyse
      the oxidation and oxidative cross-linking of l-tyrosine (l-Y) and tyrosine side
      chains in GYG and EGVYVHPV peptides, in bovine serum albumin (BSA) and beta
      casein proteins as well as in proteinaceous wool fibres was studied by oxygen
      consumption measurement, sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE), reverse phase high-performance liquid chromatography
      (RP-HPLC), matrix assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) and fluorescence microscopy. TrTyr was compared to
      the well-characterised tyrosinase from Agaricus bisporus (AbTyr) in terms of
      oxidation and cross-linking. According to the results obtained TrTyr was capable
      of cross-linking peptides and proteins more efficiently than AbTyr. However, the
      size and three-dimensional structure of the proteinaceous substrates proved to be
      crucial for the success of the enzymatic catalysis. Random coil beta-casein could
      be cross-linked by TrTyr already in three hours, but large and compact BSA was
      not cross-linked even in 24h. TrTyr could also be used to incorporate a
      diphenolic compound, l-dihydroxyphenyl alanine (l-dopa), into protein fibres
      whereas incorporation of a monophenol, l-Y was less efficient. Thus TrTyr is a
      potential tool for protein cross-linking and/or modification.

PMID- 18054404
TI  - Amino acid substitutions in alphaA and alphaC of Cyt2Aa2 alter hemolytic activity
      and mosquito-larvicidal specificity.
AB  - Cyt2Aa2 produced by Bacillus thuringiensis subsp. darmstadiensis exhibits in
      vitro cytolytic activity against broad range of cells but shows specific in vivo
      toxicity against larvae of Dipteran insects. To investigate the role of amino
      acids in alphaA and alphaC of this toxin, 3 single-point mutants (A61C, S108C and
      V109A) were generated. All 3 mutant proteins were highly produced as inclusion
      bodies that could be solubilized and activated by proteinase K similar to that of
      the wild type. Hemolytic activity of A61C and S108C mutants was significantly
      reduced whereas the V109A mutant showed comparable hemolytic activity to the wild
      type. Interestingly, the A61C mutant exhibited high larvicidal activity to both
      Aedes aegypti and Culex quinquefasciatus. S108C and V109A mutants showed low
      activity against C. quinquefasciatus but relatively high toxicity to A. aegypti.
      These results demonstrated for the first time that amino acids in alphaA and
      alphaC are involved in the selectivity of the Cyt toxin to the targeted organism.

PMID- 18054405
TI  - Detection of ovine herpesvirus 2 major capsid gene transcripts as an indicator of
      virus replication in shedding sheep and clinically affected animals.
AB  - The aim of this study was to identify tissues where ovine herpesvirus 2 (OvHV-2)
      replication occurs in vivo. A reverse-transcriptase PCR targeting the OvHV-2
      major capsid protein gene (ORF 25) was developed and the presence of transcripts
      used as an indicator of virus replication in naturally infected sheep, and cattle
      and bison with sheep-associated malignant catarrhal fever (SA-MCF). ORF 25
      transcripts were detected in 18 of 60 (30%) turbinate, trachea, and lung samples
      from five sheep experiencing a shedding episode; 12 of the 18 positive samples
      were turbinates. ORF 25 transcripts were not detected in any other tissue from
      the shedding sheep (n=55). In contrast, 86 of 102 (84%) samples from clinically
      affected bovine and bison tissues, including brain, kidney, intestine, and
      bladder, had ORF 25 transcripts. The data strongly suggest that OvHV-2
      replication is localized to the respiratory tract of shedding sheep,
      predominantly in the turbinate, while it occurs in virtually all tissues of
      cattle and bison with SA-MCF. These findings represent an important initial step
      in understanding viral pathogenesis, and in potentially establishing a system for
      OvHV-2 propagation in vitro.

PMID- 18054406
TI  - Cytoplasmic vacuolization responses to cytopathic bovine viral diarrhoea virus.
AB  - Bovine Viral Diarrhea Virus (BVDV) is a positive sense, single-stranded RNA virus
      which exhibits two biotypes in standard cell culture systems. The cytopathic
      strains of this virus (cpBVDV) induce dramatic cytoplasmic vacuolization in cell
      cultures, while infection with the non-cytopathic (NCP-BVDV) strains produces no
      overt changes in the host cells. Our results show that extensive cytoplasmic
      vacuolization is the earliest morphological change in response to cpBVDV
      infection in MDBK cells. Cells with extensive vacuolization showed no co-existing
      chromatin condensation, caspase activation, or loss of membrane integrity. In
      addition, the caspase inhibitor (zVAD-fmk), although improving cell viability of
      infected cells from 6.7+/-2.2% to 18.8+/-2.2%, did not prevent vacuolization. On
      the ultrastructural level, the virus-induced cytoplasmic vacuoles are single
      membrane structures containing organelles and cellular debris, which appear
      capable of fusing with other vacuoles and engulfing surrounding cytoplasmic
      materials. LysoTracker Red which marks lysosomes did not stain the virus-induced
      cytoplasmic vacuoles. In addition, this lysosomal dye could be observed in the
      cytoplasm of vacuolized cells, suggesting a lysosomal abnormality. Our data
      demonstrate that cpBVDV induced a novel cell death pathway in MDBK cells that is
      primarily associated with lysosomal dysfunction and the formation of phagocytic
      cytoplasmic vacuoles, and this mode of cell death is different from apoptosis and
      necrosis.

PMID- 18054407
TI  - Fibroblast growth factors and Hedgehogs: at the heart of the epicardial signaling
      center.
AB  - Over the past several years, increasing attention has been focused on
      understanding signaling pathways that control key events during midgestational
      heart development. During this period of development, the heart tube transforms
      into a functioning organ that must maintain its own blood supply and grow and
      respond to the physiologic needs of the organism. A critical event that occurs
      during midgestational heart development is the formation of the epicardium, which
      functions as a source of cells and as a signaling center that regulates
      myocardial growth and coronary vascular development. This review will describe
      our understanding of the role and the mechanism by which the epicardium governs
      these developmental events, primarily as a result of studies in the mouse. We
      focus on two key growth factor pathways: fibroblast growth factor and Hedgehog
      signaling.

PMID- 18054408
TI  - Phase II study of plitidepsin in pretreated patients with locally advanced or
      metastatic non-small cell lung cancer.
AB  - OBJECTIVE: To evaluate the progression-free rate (PFR) at 3 months (13+/-1
      weeks), antitumor response, time-to-event efficacy endpoints, and toxicity
      profile of plitidepsin administered as a 3-h continuous i.v. infusion at a dose
      of 5mg/m(2), every 2 weeks, to patients with chemotherapy pretreated advanced non
      small cell lung cancer (NSCLC). PATIENTS AND METHODS: This was a multicenter, non
      randomized, exploratory, phase II study. Treatment lasted until disease
      progression, unacceptable toxicity, patient refusal or treatment delay for >2
      weeks. PFR (primary efficacy endpoint) and objective response rate (secondary
      efficacy endpoint) were evaluated according to RECIST, while the toxic profile of
      plitidepsin was assessed using the NCI-CTC, version 2.0. RESULTS: A total of 21
      patients with a median age of 61 years and with locally advanced or metastatic
      non-resectable NSCLC, who had previously received only one line of chemotherapy
      in an advanced setting, received a total of 54 cycles of treatment (median of two
      cycles per patient; range: 1-8). Antitumor activity was seen in 3 (1 PR, 2 SD)
      out of 17 evaluable patients according to RECIST. One patient was responder for
      the primary (PFR at 13+/-1 weeks) and secondary efficacy endpoint (stable disease
      according to RECIST). Other two patients were non-responders for the primary
      efficacy endpoint, but had stable disease (not confirmed at weeks 13+/-1 due to
      previous withdrawal due to adverse events). With a median follow-up of 12.3
      months, the median time to progression (TTP) and the median overall survival (OS)
      were 1.2 months and 4.3 months, respectively. The incidence of plitidepsin
      related toxicities was low and most of them were mild-to-moderate in severity.
      The most common side effects were anemia, and asymptomatic and non-cumulative
      increases of gamma-glutamyltransferase (GGT) and liver transaminase levels.
      CONCLUSION: This study shows that plitidepsin 3-h continuous i.v. infusion
      (5mg/m(2)) every 2 weeks, was feasible and well tolerated in patients with
      pretreated NSCLC. The lack of evidence of antitumor activity precludes further
      studies with this plitidepsin schedule in this tumor setting.

PMID- 18054409
TI  - Competition between targeting signals in hybrid proteins provides information on
      their relative in vivo affinities for subcellular compartments.
AB  - After their translation and folding in the cytoplasm, proteins may be imported
      into an organelle, associate with a membrane, or rather become part of large,
      highly localised cytoplasmic structures such as the cytoskeleton. The
      localisation of a protein is governed by the strength of binding to its immediate
      target, such as an import receptor for an organelle or a major component of the
      cytoskeleton, e.g. actin. We have experimentally provided a set of actin-binding
      proteins with competing targeting information and expressed them at various
      concentrations to analyse the strength of the signal that governs their
      subcellular localisation. Our microscopic observations indicate that organellar
      sorting signals override the targeting preference of most cytoskeletal proteins.
      Among these signals, the nuclear localisation signal of SV40 is strongest,
      followed by the oligomerised PHB domain that targets vacuolin to the endosomal
      surface, and finally the tripeptide SKL mediating transport into the peroxisome.
      The actin-associated protein coronin, however, can only be misled by the nuclear
      localisation signal. Interestingly, the targeting behaviour of this model set of
      hybrid proteins in living Dictyostelium amoebae correlates surprisingly well with
      the affinities of their constituent signals derived from in vitro experiments
      conducted in various other organisms. Accordingly, this approach allows
      estimating the in vivo affinity of a protein to its target even if the latter is
      not known, as in the case of vacuolin.

PMID- 18054410
TI  - [Hemoglobin targets in anemic patients with chronic kidney disease treated with
      erythropoietin].
AB  - PURPOSE: Erythropoietin is the treatment of the anaemia in chronic kidney
      disease. A target rate of haemoglobin higher than 11 g/dl was usually proposed,
      but recent recommendations stated that higher limit of haemoglobin was to be
      reached, with the aim to improve the quality of life of the patients and to
      reduce their risks of cardiovascular diseases. These objectives are to be
      revised, according to the results of recently published clinical trials. CURRENT
      KNOWLEDGE AND KEY POINTS: Patients treated to reach a high rate of haemoglobin
      (between 13 and 14,5 g/dl) have an improved quality of life, but a 30% higher
      mortality rate, compared to patients treated with a lower objective of
      haemoglobin rate (10-12 g/dl). Hypertension and vascular access thromboses were
      also more frequent in the patients with the highest haemoglobin rate. Two to
      three times more erythropoietin was necessary to reach the higher rate of
      haemoglobin. These results favour a target rate of haemoglobin not higher than 12
      g/dl. A polemic followed the results of these clinical trials, mostly in the
      United States, questioning the way in which the higher limit had been fixed
      whereas precise data were unavailable. The role of pharmaceutical industry and of
      for profit dialysis centres was underlined. FUTURE PROSPECTS AND PROJECTS: The
      next step is now to explain if the excess in cardiovascular morbimortality is
      related to the haemoglobin rate or to a direct effect of the erythropoietin. Such
      an understanding is important, the more so as new erythropoiesis-stimulating
      agents are being developed.

PMID- 18054411
TI  - [Cervical pain with fever].

PMID- 18054412
TI  - A comparison of problem-based and traditional education on nursing students'
      critical thinking dispositions.
AB  - Determining the critical thinking (CT) levels of students in undergraduate
      nursing schools is important in terms of establishing the methods of education
      that should be used. Although there is some evidence that active learning
      approaches like problem-based learning are effective in developing CT, the
      findings are inconclusive. This descriptive analytic study compared levels of
      critical thinking among senior nursing students (N=147) in two educational
      programs, one of which used a problem-based learning (PBL) model while the other
      used a traditional model. The California critical thinking disposition inventory
      (CCTDI) was used as a data collection tool. Comparisons between the groups were
      made using t-test analysis. There was a significant difference (p<0.05) between
      the critical thinking disposition scores of the seniors in the PBL school and
      those in the school implementing the traditional model. Analysis of sub-scale
      scores showed significant differences in truth-seeking and open-mindedness. These
      findings add to the evidence that the active and self-directed nature of PBL
      encourages students' ability to think critically, be tolerant of the ideas of
      others and evaluate conflicting information before reaching a conclusion.

PMID- 18054413
TI  - Surface-displayed porcine epidemic diarrhea viral (PEDV) antigens on lactic acid
      bacteria.
AB  - In this report, for surface display of viral antigen on lactobacilli, we have
      developed a surface antigen display system using the poly-gamma-glutamate
      synthetase A protein (pgsA) of Bacillus subtilis as an anchoring matrix.
      Recombinant fusion proteins comprised of pgsA and neucleocapsid protein of PEDV
      were stably expressed in Lactobacillus casei. Surface location of fusion protein
      was verified by ELISA, immunofluoresence microscopy. Oral and intranasal
      inoculations of recombinant L. casei into pregnant sow and mice resulted in high
      levels of serum immunoglobuline G (IgG) and mucosal IgA, as demonstrated by
      rnELISA(recombinant N protein ELISA) using recombinant N protein. Absorbance of
      IgG in pregnant sow sera highly increased duration of the experiment. More
      importantly, the level of IgA in colostrum were increased significantly higher
      than that of IgG. The IgG levels of the piglets were increased after suckling
      colostrum secreted from sows previously inoculated recombinant L. casei. These
      results indicate that mucosal immunization with recombinant L. casei expressing
      PEDV N protein (neucleoprotein of PEDV) on its surface elicited high levels of
      mucosal IgA and circulation IgG immune responses against the antigen N of PEDV.

PMID- 18054414
TI  - Development and characterization of a standardized ELISA including a reference
      serum on each plate to detect antibodies induced by experimental malaria
      vaccines.
AB  - Enzyme linked immunosorbent assay (ELISA) has been widely used to measure
      antibody titers for evaluating the immunogenicity of a vaccine. However, there is
      as yet no generally accepted way of expressing the ELISA results in the case of
      experimental vaccines, since there is usually no uniform standard. Both end point
      and single dilution methods have significant disadvantages. In this paper, we
      obtained reproducible data with fewer dilutions of samples by addition of
      serially diluted standard serum to each ELISA plate. Since this ELISA method
      gives reliable antibody titer with less labor than other methods, it can strongly
      support vaccine development.

PMID- 18054415
TI  - Allergen immunotherapy in intermittent allergic rhinitis reduces the
      intracellular expression of IL-4 by CD8+ T cells.
AB  - BACKGROUND: T helper subset dysregulation is evident in allergic disorders. The
      role of T cytotoxic subsets is less understood. We investigated whether allergen
      immunotherapy in intermittent allergic rhinitis influences the intracellular
      expression of IL-4 and IFN-gamma by CD3+CD8(-) and CD3+CD8+ cells. METHODS:
      Nineteen adult patients with intermittent allergic rhinitis were evaluated before
      the pollen season, and then after one preseasonal course of subcutaneous allergen
      immunotherapy. Twelve healthy nonatopic patients matched for age and sex served
      as controls. Intracellular expression of IFN-gamma and IL-4 by CD3+CD8(-) (Th1
      and Th2, respectively) and CD3+CD8+ (Tc1 and Tc2, respectively) was estimated by
      flow cytometry in peripheral blood cells after stimulation with PMA and
      ionomycin. RESULTS: Before immunotherapy the percentages of Th1, Th2, Tc1 and Tc2
      did not significantly differ between the patients and the controls. After
      immunotherapy the percentage of Tc2 was lower in the rhinitic patients than in
      the controls (0.38% vs. 0.45%, p=0.04). The percentage of Tc2 cells decreased
      significantly after immunotherapy in the intermittent allergic rhinitis group
      (0.64% vs. 0.38%, p=0.02) with tendency to decrease in ratios of Tc2/Tc1
      (p=0.059) and with no changes in ratios of Th2/Th1. The percentages of Th1, Th2
      and Tc1 were comparable before and after immunotherapy within the rhinitic
      patient group. CONCLUSIONS: The preseasonal allergen subcutaneous immunotherapy
      applied to intermittent allergic rhinitis patients suppressed the percentage of
      IL-4 producing CD3+CD8+ cells. Decreased number of CD3+CD8+IL-4+ cells may
      participate in the regulatory mechanisms of immunotherapy.

PMID- 18054416
TI  - Orthopaedic sport biomechanics - a new paradigm.
AB  - This article proposes a new paradigm, "Orthopaedic sport biomechanics", for the
      understanding of the role of biomechanics in preventing and managing sports
      injury. Biomechanics has three main roles in this paradigm: (1) injury
      prevention, (2) immediate evaluation of treatment, and (3) long-term outcome
      evaluation. Related previous studies showing the approach in preventing and
      managing anterior cruciate ligament rupture and anterior talofibular ligament
      tear are highlighted. Orthopaedics and biomechanics specialists are encouraged to
      understand what they could contribute to the current and future practice of
      sports medicine.

PMID- 18054417
TI  - Plasma folate level, urinary arsenic methylation profiles, and urothelial
      carcinoma susceptibility.
AB  - To elucidate the influence of folate concentration on the association between
      urinary arsenic profiles and urothelial carcinoma (UC) risks in subjects without
      evident arsenic exposure, 177 UC cases and 488 controls were recruited between
      September 2002 and May 2004. Urinary arsenic species including inorganic arsenic,
      monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) were determined
      by employing a high performance liquid chromatography-linked hydride generator
      and atomic absorption spectrometry procedure. After adjustment for suspected risk
      factors of UC, the higher indicators of urinary total arsenic levels, percentage
      of inorganic arsenic, percentage of MMA(V), and primary methylation index were
      associated with increased risk of UC. On the other hand, the higher plasma folate
      levels, urinary percentage of DMA(V) and secondary methylation index were
      associated with decreased risk of UC. A dose-response relationship was shown
      between plasma folate levels or methylation indices of arsenic species and UC
      risk in the respective quartile strata. The plasma folate was found to interact
      with urinary arsenic profiles in affecting the UC risk. The results of this study
      may identify the susceptible subpopulations and provide insight into the
      carcinogenic mechanisms of arsenic even at low arsenic exposure.

PMID- 18054420
TI  - Maca (Lepidium meyenii) and yacon (Smallanthus sonchifolius) in combination with
      silymarin as food supplements: in vivo safety assessment.
AB  - Yacon and maca are native Andean crops with growing popularity as food
      supplements often in combination with other components, e.g. silymarin. There are
      however no published data on their toxicity and safety in humans. The aim of our
      randomized placebo-controlled 90-day study was to evaluate the effects of yacon
      and maca in combination with silymarin on plasma and lipoprotein lipids, serum
      glucose and safety parameters in patients suffering from the metabolic syndrome.
      No adverse effects were found in volunteers using silymarin (0.8 g/day),
      silymarin+yacon (0.8+2.4 g/day) and silymarin+maca (0.6+0.2 g/day). A moderate
      AST level and diastolic blood pressure increase was found in volunteers using
      maca (0.6 g/day). In conclusion, the combination silymarin+yacon appears to be
      promising as a nutraceutical in the prevention of diseases with a proatherogenic
      lipoprotein profile and liver steatosis. The effect of maca on AST level and
      blood pressure must be considered when using high doses of maca powder. This
      effect could be reversed by supplementation with silymarin.

PMID- 18054421
TI  - Re: Genotoxic effects of aluminum chloride in cultured human lymphocytes treated
      in different phases of cell cycle.

PMID- 18054422
TI  - [Post-traumatic lumbar hernia and abdominal wall reconstruction technique. A case
      report].
AB  - INTRODUCTION: Little less than half of the occurrences acquired lumbar hernias
      are caused by traumatisms: direct parietal contusions, iliac crest biopsies or
      fractures. Regarding their frequency, they are rare but generally underdiagnosed.
      Abdominal wall reconstruction is motivated by the risk of hernia strangulation,
      but also aims to rebuild continent abdominal muscles, allowing the loss of
      discomfort or worsening risk as well as to resume physical activities. MATERIAL
      AND METHODS: We report a case of parietal reconstruction of a traumatism-induced
      lumbar hernia in a 59-year-old male patient. Scanner showed lumbar disinsertion
      of abdominal transversus and both obliquus externus and internus muscles. The
      pressure exerted on abdominal muscles, greater than the elastic resistance of the
      insertion aponeurosis, caused their tearing. The flexibility and elasticity of
      the skin allowed the sustainment of its integrity. We applied Welti-Eudel's
      technique to suture the dorsal edge of the transverse and oblique intern muscles
      with a flap coming from lumbo-dorsal fasciae of sacrospinalis muscles. A parietal
      prosthesis is inserted between this deep level and the obliquus externus, which
      is restored. RESULTS: Fifteenth month's results, both morphological and
      functional, are excellent. Check scanner shows anatomical restitution of
      abdominal muscles. CONCLUSION: The scanner of abdominal muscles is the leading
      complementary exam. It is repeated with a gap, so that the hematoma does not
      disturb its interpretation. Surgical indication is definite for active adults.
      Parietal prosthetic strengthening, bone inserted between two muscular levels,
      avoid late loosening. It has no immediate mechanical value, which is secured by
      abdominal girdle during healing.

PMID- 18054423
TI  - Vulnerability and risk evaluation of agricultural nitrogen pollution for
      Hungary's main aquifer using DRASTIC and GLEAMS models.
AB  - In recent years, the significant improvement in point source depuration
      technologies has highlighted problems regarding, in particular, phosphorus and
      nitrogen pollution of surface and groundwater caused by agricultural non-point
      (diffuse) sources (NPS). Therefore, there is an urgent need to determine the
      relationship between agriculture and chemical and ecological water quality. This
      is a worldwide problem, but it is particularly relevant in countries, such as
      Hungary, that have recently become members of the European Community. The Italian
      Foreign Ministry has financed the PECO (Eastern Europe Countries Project)
      projects, amongst which is the project that led to the present paper, aimed at
      agricultural sustainability in Hungary, from the point of view of NPS.
      Specifically, the aim of the present work has been to study nitrates in Hungary's
      main aquifer. This study compares a model showing aquifer intrinsic vulnerability
      to pollution (using the DRASTIC parameter method; Aller et al. [Aller, L.,
      Truman, B., Leher, J.H., Petty, R.J., 1986. DRASTIC: A Standardized System for
      Evaluating Ground Water Pollution Potential Using Hydrogeologic Settings. US
      NTIS, Springfield, VA.]) with a field-scale model (GLEAMS; Knisel [Knisel, W.G.
      (Ed.), 1993. GLEAMS--Groudwater Leaching Effects of Agricultural Management
      Systems, Version 3.10. University of Georgia, Coastal Plain Experimental Station,
      Tifton, GA.]) developed to evaluate the effects of agricultural management
      systems within and through the plant root zone. Specifically, GLEAMS calculates
      nitrate nitrogen lost by runoff, sediment and leachate. Groundwater monitoring
      probes were constructed for the project to measure: (i) nitrate content in
      monitored wells; (ii) tritium (3H) hydrogen radioisotope, as a tool to estimate
      the recharge conditions of the shallow groundwater; (iii) nitrogen isotope ratio
      delta15N, since nitrogen of organic and inorganic origin can easily be
      distinguished. The results obtained are satisfactory, above all regarding the
      DRASTIC evaluation method, which is shown to satisfactorily explain both low and
      high aquifer vulnerability, and furthermore proves to be a good tool for zoning
      hydrogeological regions in terms of natural system susceptibility to pollution.
      The GLEAMS model, however, proves not to be immediately usable for predictions,
      above all due to the difficulty in finding sufficient data for the input
      parameters. It remains a good tool, but only after an accurate validation, for
      decision support systems, in the specific case to integrate intrinsic
      vulnerability, from DRASTIC (or similar methods), with land use nitrate loads
      from GLEAMS, or similar methods. The PECO project has proved a positive
      experience to highlight the fundamental points of a decision support system,
      aimed to mitigate the nitrate risk for groundwater coming from Hungarian
      agricultural areas.

PMID- 18054424
TI  - Management of the failure of a permanently implanted urethral stent-a therapeutic
      challenge.
AB  - OBJECTIVES: To demonstrate the surgical challenges posed and strategies that can
      be adopted to deal with failed stent insertion after prior urethroplasty or
      traumatic injury to the urethra. METHODS: A case series of 14 patients (mean age,
      48 yr; range, 32-61) who developed a urethral restenosis after urethral stent
      insertion into a stricture that either occurred after blunt trauma or recurred
      after a failed urethroplasty. RESULTS: In 9 of 14 patients, stricture formation
      was attributed to blunt trauma, and in the remaining 5 patients, the stricture in
      3 was secondary to a failed previous urethroplasty for a hypospadiac deformity
      and, in 2, occurred after a failed urethroplasty performed for other indications.
      The mean duration for a stent to remain in situ prior to its removal due to
      failure was 26 mo (range, 3-85). The mean follow-up period for this group of
      patients was 37 mo (range, 14-72). Four patients who had undergone urethroplasty
      prior to stent insertion required more than two interventional procedures to make
      them stricture free. CONCLUSIONS: Our findings indicate that failure of a
      permanently implanted stent represents a major surgical challenge. Implantation
      of these stents should be avoided for strictures that recur after either blunt
      trauma or surgical trauma to the urethra associated with a prior urethroplasty.
      In this series buccal mucosa was used as a graft for substitution in four
      patients, and all patients in this group were rendered stricture free without the
      need for any additional procedures.

PMID- 18054425
TI  - ALS, mercury exposure, and chelation therapy.

PMID- 18054426
TI  - Aberrant expression of selenoproteins in the progression of colorectal cancer.
AB  - Since damage to DNA and other cellular molecules by reactive oxygen species ranks
      high as a major culprit in the onset and development of colorectal cancer, the
      aim of the present study is to clarify the role of antioxidant seleonoproteins
      including glutathione peroxidase (GPx), thioredoxin reductase (TXR) and
      selenoprotein P (SePP), and the effect of oxidative stress on the progression of
      colorectal cancer. Expression of 14 oxidative stress-related molecules in both
      tumorous and non-tumorous tissues in 41 patients was examined by
      immunohistochemistry and Western blot analysis. Expression levels of proteins
      modified by 4-hydroxy-2-nonenal (4-HNE), malonyldialdehyde (MDA) and 4-hydroxy-2
      hexenal (4-HHE), and the positive rate of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in
      tumorous tissues were much higher than those in non-tumorous tissues. Glutathione
      (GSH) content in tumor tissues was much lower than that in non-tumorous tissues.
      Expression level of selenoproteins such as GPx-1, GPx-3, and SePP, which are
      rapidly degraded during selenium deprivation, was significantly decreased in
      tumorous tissues, whereas that of GPx-2, which is resistant to selenium
      deprivation, was increased. Expression of SePP was decreased at stage III and IV,
      compared to that of stage II. These data suggest that contrasting expression
      pattern of the antioxidant selenoproteins plays an important role in the
      progression of colorectal cancer.

PMID- 18054427
TI  - Biodegradability enhancement of purified terephthalic acid wastewater by
      coagulation-flocculation process as pretreatment.
AB  - In this work, the coagulation-flocculation process was used as pretreatment for
      purified terephthalic acid (PTA) wastewater with the objective of improving its
      overall biodegradability. PTA production generates wastewaters with toxicants p
      xylene [1,4-dimethyl-benzene (C8H10)], a major raw material used in the
      production process, along with some of the intermediates, viz., p-toluic acid,
      benzoic acid, 4-carboxybenzaldehyde, phthalic acid and terephthalic acid. These
      compounds affect the bio-oxidation process of wastewater treatment; hence removal
      of these constituents is necessary, prior to conventional aerobic treatment. This
      paper addresses the application of coagulation-flocculation process using
      chemical coagulants, viz., aluminium sulphate (alum), polyaluminium chloride
      (PAC), ferrous sulphate and ferric chloride in combination with anionic
      polyelectrolyte. Polyaluminium chloride (PAC) in conjunction with lime and
      polyelectrolyte removed about 63.1% chemical oxygen demand (COD) and 45.2%
      biochemical oxygen demand (BOD) from PTA wastewater. Coagulation-flocculation
      process coupled with aerobic bio-oxidation treatment of PTA wastewater achieved,
      COD & BOD removals of 97.4% and 99.4%, respectively. The biodegradability
      enhancement evaluated in terms of the BOD5/COD ratio, increased from 0.45 to 0.67
      at the optimum conditions. The results obtained from these studies indicate that
      the coagulation-flocculation process could be a suitable pretreatment method in
      reducing toxicity of PTA wastewater whilst enhancing biodegradability for aerobic
      biological treatment scheme.

PMID- 18054428
TI  - Borosilicate glasses modified with organic ligands: a new selective approach for
      the removal of uranyl ion.
AB  - Barium borosilicate glass was found to have high uptake capacity for many
      cations. To improve its selectivity, surface modification was carried out. In
      order to make the glass selective towards uranyl ion, organic ligands like tri-n
      octylphosphine oxide (TOPO) and 8-hydroxy quinoline (Oxine) were used. It was
      observed that the surface modification resulted in the change in uptake property
      of the glass. The uptake process was faster and within 5 h, 90% of the uranyl ion
      could be taken up from a 0.01 mM solution. With use of the modified barium
      borosilicate glass and EDTA as masking agent, uranyl ion could be selectively
      removed from mixtures of cations.

PMID- 18054429
TI  - Selectivity modification by ion memory of magneso-silicate and magnesium alumino
      silicate as inorganic sorbents.
AB  - Synthetic magneso-silicate and magnesium alumino-silicate as inorganic ion
      exchange materials with the formula MgSi5.59O(12.18).5.93H2O and
      MgAl2.32Si5.2O(14.88).18.23H2O, respectively, have been found to be suitable for
      the removal of Cs+, Co2+ and Eu3+ ions with the selectivity sequence
      Eu3+>Co2+>Cs+. Samples of Cs-, Co- and Eu-loaded were prepared and thermally
      treated at 850 degrees C in a furnace for the creation of specific cavity.
      Surface area, IR and X-ray diffraction patterns of the products were conducted.
      Surface area values of OMS, OMAS, TMS, TMAS, ETMS and ETMAS were measured and
      indicated an increasing in the surface area values for the TMS and TMAS samples
      and decreasing in the ETMS and ETMAS samples. Desorption studies in nitric acid
      medium were carried out and reloading of the eluted solids with the studied
      cations were conduced and the data show an ion memory behaviour for the eluted
      solids. Finally, the rate of Cs+ ion sorption on OMS, OMAS, ETMS and ETMAS was
      studied. The diffusion coefficients calculated indicated that the diffusion of
      Cs+ ion is high for the ETMS and ETMAS samples compared to the OMS and OMAS
      samples.

PMID- 18054430
TI  - Phospholipid fatty acid analysis to monitor the co-composting process of olive
      oil mill wastes and organic household refuse.
AB  - The co-composting of olive oil mill wastes and household refuse was followed for
      5 months. During the thermophilic phase of composting, the aerobic heterotrophic
      bacteria (AHB) count, showed a significant rise with a slight regression of
      fungal biomass. In the same way, phospholipid fatty acids PLFAs common in
      bacteria, showed a significant increase of hydroxyl and branched PLFAs. The
      evaluation of the ratio of octadecenoic PLFAs to stearic acid (C18:1omega/C18:0)
      revealed a significant reduction while a significant rise in the length of
      aliphatic chains evaluated by the stearic acid to palmitic acid ratio
      (C18:0/C16:0) was noted during the stabilization phase. The follow-up of PLFAs,
      indicates the degree of biodegradation that occurs during composting, it can be
      regarded an indicator of the stability and maturity of the end product.

PMID- 18054431
TI  - Modification of rice hull and sawdust sorptive characteristics for remove heavy
      metals from synthetic solutions and wastewater.
AB  - In this work two modified agricultural residues, rice hull and sawdust were
      examined as sorbents to remove heavy metals Pb(II), Cd(II), Zn(II), Cu(II) and
      Ni(II) from synthetic solutions or wastewater samples. To modify their sorptive
      characteristics, samples were treated with HCl, NaOH and heat. The sorption of
      the heavy metals from the synthetic solutions was increased with pH and initial
      concentration. In pH 5, Pb(II) and Cd(II) showed the highest sorption and Cu(II),
      Zn(II) and Ni(II) showed the following orders, respectively. Sorption capacity of
      rice hull was higher than sawdust. The modifications changed the sorption
      capacity of the natural sorbents in the following order base>heat>natural>acid.
      The sorption isotherms of sorbents were best described by the Freundlich and
      Langmuir models. The basic treated rice hull and sawdust followed by the heat
      treated rice hull sorbed the maximum of heavy metals from the industrial
      wastewater samples. In the column experiment, the synthetic solutions and the
      wastewater samples gave almost the same results as the suspensions. The recovery
      of the columns using water and HCl showed positive results. Commercial sorbents
      removed Pb(II), Zn(II) and Ni(II) a little more than rice hull.

PMID- 18054432
TI  - Low-temperature plasma-induced degradation of aqueous 2,4-dinitrophenol.
AB  - The degradation behavior of 2,4-dinitrophenol (DNP) by low-temperature plasma was
      investigated and the effect of some factors that might affect the degradation
      process was further examined. The results indicated that DNP could be effectively
      removed from aqueous solution. The degradation value was 83.6% when the input
      power was 150 W and 60 s was selected as the discharge time. Increasing the input
      power increased the degradation efficiency. The degradation process fitted first
      order dynamics and the reduction was mainly caused by the reaction of DNP with
      OH. The degradation efficiency decreased with the increase of initial
      concentration at the same discharge time. H2O2 at the concentration of 0.25%
      enhanced the degradation process, however, hindered the degradation at 1.00 and
      2.00%. The presence of Fe2+ could benefit DNP degradation. However, the increment
      in degradation efficiency might be suppressed to some extent at a high
      concentration level. Cu2+ inhibited the degradation process within 30 s and
      enhanced the reduction after 30 s. Furthermore, the increment of Cu2+
      concentration could enhance the effect. A little acid environment was conducive
      to DNP degradation and the pH value became lower with increasing discharge time
      by low-temperature plasma.

PMID- 18054433
TI  - Corporate crisis management managing a major crisis in a chemical facility.
AB  - Chemical sites should have well trained and organized emergency response plans to
      manage an incident within the plant or during transport. The implementation of an
      incident command system utilizing either internal resources or external response
      through mutual aid agreements is generally sufficient to address the direct
      impact of an event on the site. When the site resources become overwhelmed in
      addressing resulting issues such as press releases, medical advice/support,
      employees and family support, Agency notifications, etc, Corporate should be
      ready and able to respond. This paper, taken from an in-depth CCPS workshop led
      by the author, describes an outline for corporate assistance in the event of a
      major incident at a site or during transportation.

PMID- 18054434
TI  - Regulation of SULT2B1a (pregnenolone sulfotransferase) expression in rat C6
      glioma cells: relevance of AMPA receptor-mediated NO signaling.
AB  - The neurosteroid pregnenolone sulfate (PREGS), which is synthesized in glial
      cells, plays a significant role in learning and memory performance. The aim of
      this study was to investigate the regulation of expression of the steroid
      sulfotransferase SULT2B1a, which catalyzes the conversion of pregnenolone to
      PREGS, using the rat C6 glioma cell line. Rat C6 glioma cells expressed the
      SULT2B1a isoform, which sulfonates pregnenolone, but, neither the SULT2B1b
      isoform, which catalyzes cholesterol, nor the prototypical steroid
      sulfotransferase SULT2A1 were expressed in these cells. Increasing concentrations
      of l-glutamic acid in the presence of cyclothiazide, which prevents AMPA receptor
      desensitization, attenuated SULT2B1a mRNA expression; however, neither NMDA nor
      kainic acid had a significant effect. Exposure to the synthetic glutamate
      analogue alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the
      presence of cyclothiazide also inhibited SULT2B1a expression. Attenuation of
      SULT2B1a expression by L-glutamic acid was reversed by the selective AMPA/kainate
      receptor antagonist 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), and
      partially reversed by the specific neuronal nitric oxide synthase (NOS) inhibitor
      7-nitroindazole (7-NI). Induction of inducible NOS by TNF-alpha in combination
      with lipopolysaccharide (LPS) dramatically attenuated SULT2B1a expression; this
      was partially reversed by the specific inducible NOS inhibitor N(6)-(1
      iminoethyl)-L-lysine hydrochloride (L-NIL). Furthermore, exposure to exogenous NO
      donors inhibited SULT2B1a mRNA expression, and exposure to sodium nitroprusside,
      LPS/TNF-alpha and L-glutamic acid in combination with cyclothiazide increased the
      production of nitrite, a stable degradation product of NO. These findings suggest
      that expression of SULT2B1a, which catalyzes PREGS production, is inhibited by
      activation of excitatory amino acid receptors of the AMPA subtype, via
      facilitation of intracellular NO signaling.

PMID- 18054435
TI  - Visual preference for isochronic movement does not necessarily emerge from
      movement kinematics: a challenge for the motor simulation theory.
AB  - The aim of this experiment was to show that the visual preference for isochronic
      movements does not necessarily imply a motor simulation and therefore, does not
      depend on the kinematics of the perceived movement. To demonstrate this point,
      the participants' task was to adjust the velocity (the period) of a dot that
      depicted an elliptic motion with different perimeters (from 3 to 60 cm). The
      velocity profile of the movement conformed ("natural motions") or not ("unnatural
      motions") to the law of co-variation velocity-curvature (two-thirds power law),
      which is usually observed in the production of elliptic movements. For each
      condition, we evaluated the isochrony principle, i.e., the tendency to prefer
      constant durations of movement irrespective to changes in the trajectory
      perimeter. Our findings indicate that isochrony principle was observed whatever
      the kinematics of the movement (natural or unnatural). Therefore, they suggest
      that the perceptive preference for isochronic movements does not systematically
      imply a motor simulation.

PMID- 18054437
TI  - Tactile discrimination, but not tactile stimulation alone, reduces chronic limb
      pain.
AB  - Chronic pain is often associated with reduced tactile acuity. A relationship
      exists between pain intensity, tactile acuity and cortical reorganisation. When
      pain resolves, tactile function improves and cortical organisation normalises.
      Tactile acuity can be improved in healthy controls when tactile stimulation is
      associated with a behavioural objective. We hypothesised that, in patients with
      chronic limb pain and decreased tactile acuity, discriminating between tactile
      stimuli would decrease pain and increase tactile acuity, but tactile stimulation
      alone would not. Thirteen patients with complex regional pain syndrome (CRPS) of
      one limb underwent a waiting period and then approximately 2 weeks of tactile
      stimulation under two conditions: stimulation alone or discrimination between
      stimuli according to their diameter and location. There was no change in pain
      (100 mm VAS) or two-point discrimination (TPD) during a no-treatment waiting
      period, nor during the stimulation phase (p > 0.32 for both). Pain and TPD were
      lower after the discrimination phase [mean (95% CI) effect size for pain VAS = 27
      mm (14-40 mm) and for TPD = 5.7 mm (2.9-8. ), p < 0.015 for both]. These gains
      were maintained at three-month follow-up. We conclude that tactile stimulation
      can decrease pain and increase tactile acuity when patients are required to
      discriminate between the type and location of tactile stimuli.

PMID- 18054436
TI  - A1 and A2A receptor activation by endogenous adenosine is required for VIP
      enhancement of K+ -evoked [3H]-GABA release from rat hippocampal nerve terminals.
AB  - Vasoactive intestinal peptide (VIP) modulates GABA release from hippocampal nerve
      terminals and enhances hippocampal synaptic transmission through a pathway
      dependent on GABAergic transmission. Since VIP modulation of hippocampal synaptic
      transmission is dependent on the tonic actions of adenosine we investigated if
      endogenous adenosine could influence VIP enhancement of GABA release from
      isolated hippocampal nerve endings, and which adenosine receptors could be
      mediating this influence. When extracellular endogenous adenosine was removed
      using adenosine deaminase (ADA, 1U/ml), the enhancement (57.2+/-3.7%) caused by
      VIP on GABA release was prevented. Blockade of adenosine A(1) receptors with 1,3
      dipropyl-8-cyclopentylxanthine (DPCPX, 10nM) or of A(2A) receptors with ZM241385
      (50nM) abolished the effect of VIP. In the presence of ADA, selective A(2A)
      receptor-activation with CGS21680 (10nM) readmitted most of the enhancement
      caused by VIP on GABA release (50.7+/-5.3%). Also in the presence of ADA, A(1)
      receptor activation with N(6)-cyclopentyladenosine (CPA, 50nM) partially
      readmitted that effect of VIP (32.6+/-3.8%). In conclusion, the enhancement of
      GABA release caused by VIP in hippocampal nerve terminals is dependent on the
      tonic actions of adenosine on both A(1) and A(2A) receptors, and this action of
      adenosine is essential to VIP modulation of GABA release.

PMID- 18054438
TI  - Coupled lateral bending-torsional vibration sensitivity of atomic force
      microscope cantilever.
AB  - We study the influence of the contact stiffness and the ration between cantilever
      and tip lengths on the resonance frequencies and sensitivities of lateral
      cantilever modes. We derive expressions to determine both the effective resonance
      frequency and the mode sensitivity of an atomic force microscope (AFM)
      rectangular cantilever. Once the contact stiffness is given, the resonance
      frequency and the sensitivity of the vibration modes can be obtained from the
      expression. The results show that each mode has a different resonant frequency to
      variations in contact stiffness and each frequency increased until it eventually
      reached a constant value at very high contact stiffness. The low-order vibration
      modes are more sensitive to vibration than the high-order mode when the contact
      stiffness is low. However, the situation is reversed when the lateral contact
      stiffness became higher. Furthermore, increasing the ratio of tip length to
      cantilever length increases the vibration frequency and the sensitivity of AFM
      cantilever.

PMID- 18054439
TI  - Liver fattening during feast and famine: an evolutionary paradox.
AB  - Liver disease is one of the features of metabolic syndrome, one of the most
      occurring diseases of the twenty-first century. During food deprivation and
      starvation, adipose tissue elsewhere in the body delivers lipid components to the
      liver where they are stored as triacylglycerols (TG). Continuous and excessive
      food intake, on the other hand, leads to liver fattening (hepatic steatosis). In
      the long term this reaction is pathogenic mainly by inflammation reactions. We
      postulate the hypothesis in the evolutionary context that individuals with genes
      promoting the efficient deposition of fat during periods between famines (thrifty
      genes) in combination with a proinflammatory genotype would be favored and be
      selected during the course of evolution. Furthermore we postulate the hypothesis
      that the majority of man, living in a world were famine never comes, are
      physiologically not adapted to modern social behavior with abundance of food.

PMID- 18054440
TI  - Defective release of Hepcidin not defective synthesis is the primary pathogenic
      mechanism in HFE-Haemochromatosis.
AB  - Recent findings indicate a principal role for Hepcidin in iron homeostasis.
      Hepcidin is also thought to play a vital role in the pathogenic mechanism of
      anaemia in patients with inflammation or chronic disease. Under normal conditions
      influx and efflux of iron from duodenal enterocytes is regulated by Ferroportin.
      Ferroportin is a Hepcidin binding protein expressed in duodenal enterocytes.
      Hepcidin is a peptide synthesised in the liver and is the main regulator of iron
      homeostasis. It is a defensin like protein and exhibits anti-microbial and anti
      fungal activity. The Hepcidin gene is principally expressed in hepatocytes but to
      a lesser extent in neutrophils and macrophages. Hereditary Haemochromatosis is
      caused by disruption of iron homeostasis due to mutations in the HFE gene (C282Y
      or H63D). Unrestricted uptake of iron by duodenal enterocytes causes iron
      overload which is the hallmark of the disease. Current thinking is that defective
      Hepcidin synthesis or defective iron-sensing mechanisms leading to Hepcidin
      deficiency is the cause of iron overload in HFE-Haemochromatosis. Thus HFE
      Haemochromatosis has been described as an endocrine disease. Basal levels of
      Hepcidin appear to be normal in HFE-Haemochromatosis patients. This contradicts
      current theories of defective Hepcidin synthesis as the cause of Hereditary HFE
      Haemochromatosis. We propose that the defect in HFE-Haemochromatosis is the loss
      of Hepcidin surge in response to intake of dietary iron and is not as a result of
      reduced synthesis.

PMID- 18054441
TI  - The anti-tumor effect of allogeneic bone marrow/stem cell transplant without
      graft vs. host disease toxicity and without a matched donor requirement?
AB  - The anti-tumor immune response that occurs in allogeneic bone marrow/stem cell
      transplant (BMT) settings is capable of eradicating tumors that are resistant to
      chemotherapy/radiation treatment. This anti-tumor immune response, known as the
      graft vs. tumor (GVT) effect, is the most effective immunotherapy treatment ever
      discovered. Unfortunately, the clinical application of GVT is severely limited
      due to the intimate association of GVT with the extremely toxic and often lethal
      side-effect known as graft vs. host disease (GVHD). It is a major research focus
      in the field of BMT to develop methods to separate the beneficial GVT effect from
      the detrimental GVHD toxicity. However, due to the intimate association of these
      effects, attempts to limit GVHD also have a tendency to limit the GVT effect. We
      propose a new concept for harnessing the power of the GVT effect without the
      toxicity of GVHD. Rather than trying to separate GVT from GVHD, we propose that
      these naturally coupled effects can 'mirrored' onto the host immune system and
      maintain their intimate association. The 'mirror' of GVHD is a host rejection of
      a graft (HVG). As rejection of an allograft would not be toxic, an HVG effect
      coupled to a host vs. tumor (HVT) effect, the 'mirror' of the GVT effect, would
      provide the anti-tumor effect of BMT without GVHD toxicity. In the 'mirror'
      setting, the HVT effect must occur against syngeneic tumors, while in the BMT
      setting the GVT effect occurs in the allogeneic setting. Previous attempts to
      elicit syngeneic anti-tumor immunity using therapeutic tumor vaccines have had
      disappointing results in the clinic due to the influence of tumor immunoavoidance
      mechanisms. We propose that the 'danger' signals that are released as a result of
      GVHD in the allogeneic BMT setting serve as an adjuvant to the GVT effect
      disabling tumor immunoavoidance. The chemotherapy/radiation conditioning prior to
      transplant is a required initiating event to the coupled GVT/GVHD effects. The
      conditioning releases 'danger' signals that mediate this adjuvant effect. To
      imitate this immunological event in immunocompetent, non-conditioned patients we
      propose that infusion of freshly activated, polyclonal CD4+ memory Th1 cells
      which express CD40L on the cell surface will stimulate a HVT/HVG 'mirror' effect,
      providing a non-toxic means to elicit the effective immune-mediated anti-tumor
      effect of BMT without the GVHD toxicity and without the requirement for a matched
      donor.

PMID- 18054442
TI  - Discrete-trial vs. continuous free-operant procedures in assessing whether
      reinforcement context affects reinforcement value.
AB  - Pigeons were trained to respond to two alternating concurrent reinforcement
      schedules. The reinforcement probabilities were .05 and .10 in one component, and
      .10 and .20 in the other. In one condition, the pigeons received training on a
      discrete-trial procedure in which the keylights remained illuminated for 5s or
      until a response occurred. In another condition, pigeons received training on a
      procedure in which the reinforcement contingencies were the same as in the
      discrete-trial procedure, but the stimuli were not turned off after 5s or after a
      response. Following training in each condition, probe tests were presented. In
      both conditions, the .20 alternative was, overall, preferred to the .05
      alternative during probe tests. Following discrete-trial training, there was no
      reliable preference between the two .10 alternatives. However, when the stimuli
      remained illuminated during the intertrial interval periods during training,
      probe tests results showed preference for the .10 alternative that had been
      presented in the leaner context during training. The pattern of results is
      consistent with the notion that probe preference can be influenced both by the
      absolute reinforcement schedules associated with each alternative, as well as
      changeover behavior developed during training.

PMID- 18054443
TI  - Evaluation of a telephone-based stepped care intervention for alcohol-related
      disorders: a randomized controlled trial.
AB  - BACKGROUND: Brief interventions for problem drinking in medical settings are
      effective but rarely conducted, mainly due to insufficient time. A stepped care
      approach (starting with a very brief intervention and intensifying efforts in
      case of no success) could save resources and enlarge effectiveness; however,
      research is lacking. The present study compares a full care brief intervention
      for patients with at-risk drinking, alcohol abuse or dependence with a stepped
      care approach in a randomized controlled trial. METHODS: Participants were
      proactively recruited from general practices in two northern German cities. In
      total, 10,803 screenings were conducted (refusal rate: 5%). Alcohol use disorders
      according to DSM-IV were assessed with the Munich-Composite International
      Diagnostic Interview (M-CIDI). Eligible participants were randomly assigned to
      one of three conditions: (1) stepped care (SC): a computerized intervention plus
      up to three 40-min telephone-based interventions depending on the success of the
      previous intervention; (2) full-care (FC): a computerized intervention plus a
      fixed number of four 30-min telephone-based interventions that equals the maximum
      of the stepped care intervention; (3) an untreated control group (CG). Counseling
      effort in the intervention conditions and quantity/frequency of drinking were
      assessed at 12-month follow-up. RESULTS: SC participants received roughly half of
      the amount of intervention in minutes compared to FC participants. Both groups
      did not differ in drinking outcomes. Compared to CG, intervention showed small to
      medium effect size for at-risk drinkers. CONCLUSIONS: Study results reveal that a
      stepped care approach can be expected to increase cost-effectiveness of brief
      interventions for individuals with at-risk drinking.

PMID- 18054444
TI  - Non-prescribed use of pain relievers among adolescents in the United States.
AB  - BACKGROUND: We examined gender-specific prevalences, patterns, and correlates of
      non-prescribed use of pain relievers - mainly opioids - in a representative
      sample of American adolescents (N=18,678). METHODS: Data were drawn from the
      public use data file of the 2005 U.S. National Survey on Drug Use and Health, a
      survey of non-institutionalized American household residents. The patterns of non
      prescribed use of prescription pain relievers were examined, and logistic
      regression procedures were conducted to identify correlates of non-prescribed
      use. RESULTS: Approximately one in 10 adolescents aged 12-17 years reported non
      prescribed use of pain relievers in their lifetime (9.3% in males and 10.3% in
      females). The mean age of first non-prescribed use was 13.3 years, which was
      similar to the mean age of first use of alcohol and marijuana but older than the
      age of first inhalant use. Among all non-prescribed users, 52% reported having
      used hydrocodone products (Vicodin, Lortab, Lorcet, and Lorcet Plus, and
      hydrocodone), 50% had used propoxyphene (Darvocet or Darvon) or codeine (Tylenol
      with codeine), and 24% had used oxycodone products (OxyContin, Percocet,
      Percodan, and Tylox). Approximately one quarter (26%) of all non-prescribed users
      had never used other non-prescribed or illicit drugs. There were gender
      variations in correlates of non-prescribed use. CONCLUSIONS: Use of non
      prescribed pain relievers occurs early in adolescence. Research is needed to
      understand whether early use of non-prescribed pain relievers is related to later
      drug use.

PMID- 18054445
TI  - Brief alcohol intervention for general hospital inpatients: a randomized
      controlled trial.
AB  - AIM: To test the effectiveness of a brief alcohol intervention among non
      dependent general hospital inpatients with alcohol problems, delivered by either
      a specialized liaison service or hospital physicians. METHOD: All inpatients of
      29 wards from four general hospitals of one region in Germany were screened for
      alcohol problems (n=14,332). Of those screening positive, 595 patients were
      included in a randomized controlled group design using a time-frame. Patients
      with alcohol dependence were not considered in this study. Patients received
      Motivational Interviewing based counselling either by a specialized liaison
      service, by hospital physicians trained under routine conditions or received
      hospital treatment as usual without additional counselling. One year later,
      alcohol consumption, motivation and well-being were assessed. Sample survey
      analyses and generalized estimating equations were conducted. RESULTS: At
      baseline, the three groups differed regarding motivation, with higher motivation
      among the controls. At follow-up, the groups did not differ regarding alcohol
      consumption, alcohol-related problems and well-being. All groups decreased their
      alcohol consumption significantly. Regarding motivation, longitudinal analyses
      revealed significant interaction effects of time and intervention (p<0.05),
      indicating a stronger increase of readiness to change drinking and a less
      profound drop of readiness to seek help among those who received intervention
      compared to the controls. CONCLUSION: The intervention was not effective in
      reducing alcohol consumption or in increasing well-being 12 months after
      hospitalization. It had a positive effect on readiness to change drinking and on
      readiness to seek formal help for alcohol problems. The intervention groups
      compensated their lag of motivation.

PMID- 18054446
TI  - Acquisition of cocaine self-administration in ovariectomized female rats: effect
      of estradiol dose or chronic estradiol administration.
AB  - This study was conducted to investigate whether the dose of estradiol (E)
      administered acutely, or chronic delivery of one dose of E impacts acquisition
      and subsequent cocaine self-administration in ovariectomized (OVX) female rats.
      Five groups of female rats were compared: OVX females treated with 0, 1, 2, or 5
      microg 17beta-E, 30 min prior to the self-administration session, and OVX rats
      that received a 1.5mg E pellet (designed to chronically release 25 microg E/day X
      60 days) implanted 1 week before cocaine self-administration initiation. Rats
      were tested in 1h sessions on a FR1 schedule with the dose of cocaine increasing
      every week (testing occurred 5 day/week; doses: 0.2, 0.3, 0.4, 0.5 and 0.75
      mg/(kg infusion)). We report that OVX rats treated with 2 microg E acquired self
      administration more rapidly than all of the other groups, and animals that
      received 1 or 2 microg E self-administered significantly more cocaine compared to
      OVX+vehicle at 0.3 and 0.4 mg/(kg infusion). In contrast, OVX rats given 5 microg
      E acutely, or chronic E via slow-release pellets did not take more cocaine than
      the OVX+vehicle group at any time point. Physiological serum concentrations of E
      were seen with 1 or 2 microg E, but 5 microg E and the E pellet produced supra
      physiological concentrations. These results suggest an inverted U-shaped dose
      response curve for the effect of E on acquisition of cocaine self-administration.

PMID- 18054447
TI  - The relationship of mucosal bacteria to duodenal histopathology, cytokine mRNA,
      and clinical disease activity in cats with inflammatory bowel disease.
AB  - Feline inflammatory bowel disease (IBD) is the term applied to a group of poorly
      understood enteropathies that are considered a consequence of uncontrolled
      intestinal inflammation in response to a combination of elusive environmental,
      enteric microbial, and immunoregulatory factors in genetically susceptible cats.
      The present study sought to examine the relationship of mucosal bacteria to
      intestinal inflammation and clinical disease activity in cats with inflammatory
      bowel disease. Duodenal biopsies were collected from 27 cats: 17 undergoing
      diagnostic investigation of signs of gastrointestinal disease, and 10 healthy
      controls. Subjective duodenal histopathology ranged from normal (10), through
      mild (6), moderate (8), and severe (3) IBD. The number and spatial distribution
      of mucosal bacteria was determined by fluorescence in situ hybridization with
      probes to 16S rDNA. Mucosal inflammation was evaluated by objective
      histopathology and cytokine profiles of duodenal biopsies. The number of mucosa
      associated Enterobacteriaceae was higher in cats with signs of gastrointestinal
      disease than healthy cats (P<0.001). Total numbers of mucosal bacteria were
      strongly associated with changes in mucosal architecture (P<0.001) and the
      density of cellular infiltrates, particularly macrophages (P<0.002) and
      CD3(+)lymphocytes (P<0.05). The number of Enterobacteriaceae, E. coli, and
      Clostridium spp. correlated with abnormalities in mucosal architecture
      (principally atrophy and fusion), upregulation of cytokine mRNA (particularly IL
      1, -8 and -12), and the number of clinical signs exhibited by the affected cats.
      These data establish that the density and composition of the mucosal flora is
      related to the presence and severity of intestinal inflammation in cats and
      suggest that mucosal bacteria are involved in the etiopathogenesis of feline IBD.

PMID- 18054448
TI  - In vitro studies of Lactobacillus delbrueckii subsp. lactis in Atlantic salmon
      (Salmo salar L.) foregut: tissue responses and evidence of protection against
      Aeromonas salmonicida subsp. salmonicida epithelial damage.
AB  - Probiotic bacteria increase the host health status and protect mucosal tissue
      against pathogen-caused damage in mammalian models. Using an in vitro (intestinal
      sac) method this study aimed to address (a) the in vitro ability of Lactobacillus
      delbrueckii subsp. lactis to remain in the gastrointestinal tract of Atlantic
      salmon (Salmo salar L.) and (b) its ability to prevent cellular damage caused by
      successive incubation with Aeromonas salmonicida subsp. salmonicida the causative
      agent of furunculosis. Short in vitro incubation of salmon foregut with (TRITC)
      labelled L. delbrueckii subsp. lactis showed that the probiont was able to
      colonize the enterocyte surface as studied by confocal microscopy. Furthermore,
      foregut incubated with the probiotic bacteria only, resulted in a healthy
      intestinal barrier whereas exposure to A. salmonicida disrupted its integrity.
      However, pre-treatment of salmon intestine with L. delbrueckii subsp. lactis
      prevented Aeromonas damaging effects. These results are promising in the context
      of the use of non-autochthonous probiotic bacteria as prophylactic agents against
      fish bacterial infections in the gastrointestinal tract.

PMID- 18054449
TI  - Cloning, expression and purification of envelope proteins E1 and E2 of western
      equine encephalitis virus and potential use of them as antigens in immunoassays.
AB  - The genes encoding envelope proteins E1 and E2 of western equine encephalitis
      virus (WEEV) were respectively cloned into a prokaryotic T7 RNA polymerase
      regulated expression vector. The recombinant C-terminal 6xHis-tagged WEEV E1 and
      E2 were expressed in bacteria as inclusion bodies that were subsequently
      solubilized with 8M urea, purified by immobilized metal ion affinity
      chromatography and finally refolded using an arginine system. The purified 6xHis
      tagged proteins showed 50kDa bands as revealed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis, consistent with the expected sizes of WEEV E1
      and E2. The potential of the recombinant WEEV E1 and E2 as antigens for serologic
      tests to detect anti-WEEV antibodies for diagnosis of WEEV infection was assessed
      by an enzyme-linked immunosorbent assay with anti-WEEV polyclonal antibodies
      obtained from the mice infected with WEEV. The anti-WEEV antibodies bound the
      recombinant WEEV E1 and E2 in a dose dependent manner. On the contrary,
      antibodies against Venezuelan equine encephalitis virus with a genetic background
      and a disease spectrum very similar to WEEV, did not bind to the recombinant WEEV
      E1 and E2. Our results suggest that the recombinant WEEV E1 and E2 possess
      predominant antigenicity of WEEV and have the potential to be used as antigens in
      immunoassays to detect anti-WEEV antibodies for serological diagnosis of WEEV
      infection so as to eliminate the need for preparation of cell culture-derived
      viral antigens, which is time-consuming, expensive, laborious, tedious, and
      hazardous.

PMID- 18054450
TI  - Activation-induced cell death signalling in CD4+ T cells by staphylococcal
      enterotoxin A.
AB  - Staphylococcal enterotoxin A (SEA) is a potent stimulator of CD4+ and CD8+ T
      cells, the immunotoxic action of which remains unclear. We investigated the in
      vitro effects of SEA on freshly isolated human peripheral blood lymphocytes
      depleted of CD8+ T cells. Proliferation and flow cytometry analysis indicated
      that SEA generated an activation-induced cell death (AICD) phenomenon that was
      characterized by an increased expression of the chemokine receptor CCR5 on the
      CD4+/CD45RO+ T cell subset. Incubation of cells with glycoprotein secretion
      inhibitor monensin A completely blocked cell proliferation, affecting mainly the
      CD4+/CD45RO+ T cell subset. The IL-2 mRNA levels were increased just hours after
      SEA stimulation, accompanied by an increase in the expression of CD25, indicating
      a possible involvement of IL-2 in the AICD process. We observed a 15-fold mRNA
      reduction of the transcription factor Yin Yang 1 (YY1) at the proliferation peak,
      and an increase of the receptors CCR5, CD95 and DR5 on the CD45RO+/CD4+ T cell
      subset. These findings suggest that SEA triggers a TCR-mediated AICD mechanism in
      CD4+ T cells, the intracellular signalling of which is probably modulated, at
      least, by YY1.

PMID- 18054451
TI  - The efficacy of different hCG dose rates and the effect of hCG treatment on
      ovarian activity: ovulation, multiple ovulation, pregnancy, multiple pregnancy,
      synchrony of multiple ovulation; in the mare.
AB  - Despite the widespread use of hCG to advance ovulation in the mare there is
      little information on efficacy of dose rates and any contraindications of its
      use. This study aims to investigate the effect of dose of hCG on ovulation within
      48h and the effect of hCG on: ovulation, multiple ovulation (MO), pregnancy,
      multiple pregnancy (MP) rates and synchrony of MO; additionally whether any
      seasonal effect is evident. Sequential ultrasonic scanning was used to monitor
      the occurrence of ovulation, within 48h of treatment, in 1291 Thoroughbred mares
      treated with either 750iu hCG or 1500iu hCG s.c. Ovulation rate, type (single
      ovulations (SO), MO, synchronous, asynchronous) and subsequent pregnancy were
      then monitored in 1239 Thoroughbred mares on a commercial stud over 3 years, 536
      of which were treated with 750iu hCG at mating, all mares were also allocated
      into groups according to month of mating. No significant difference existed
      between the two dose levels of hCG and no significant difference existed between
      treated and untreated mares in overall ovulations (1.32 and 1.28 respectively),
      MO (31.7% and 27.7%), pregnancy (65.1% and 65.6%) or MP rates (10.8% and 11.8%).
      There was no significant association between month of year and pregnancy or MP
      rates for either treated or control mares, nor for MO for untreated mares. A
      significant (p<0.05) association was evident between month and MO in treated
      mares, MO being lowest in April (22.3%). 95.9% of treated mares multiple ovulated
      within 48h compared with 90.7% controls, a near significant difference. In
      conclusion this study demonstrates that: (i) hCG dose of 750iu s.c. is just as
      effective in inducing ovulation within 48h as 1500iu, (ii) 750iu hCG has no
      significant effect on ovulation, MO, pregnancy or MP rates; (iii) a significant
      (p<0.05) association exists between season and MO in hCG treated mares; (iv) a
      tighter synchrony (ovulation within 48h) of MO is evident in hCG treated compared
      with control mares (p=0.052).

PMID- 18054452
TI  - In vitro production of llama (Lama glama) embryos by IVF and ICSI with fresh
      semen.
AB  - The interest for South American camelids has increased in the last years. The aim
      of the present research was to compare the in vitro production of Lama glama
      embryos using two techniques: in vitro fertilization (IVF) and intracytoplasmic
      sperm injection (ICSI). For IVF technique, we compared the effect of adding or
      not, heparin, penicillamine and hypotaurine as sperm capacitating agents. In the
      oocyte group subjected to ICSI, activation with or without, ionomycin and 6
      dimethylaminopurine (6-DMAP) was assessed. Semen samples were obtained by
      electroejaculation and incubated at 38 degrees C in a 25% (v/v) collagenase
      solution. The cleavage and embryo development rates were compared between the
      different experimental groups. Only the number of cleaved oocytes was less when
      ICSI with no activation was used (p<0.05).

PMID- 18054453
TI  - Cryo-scanning electron microscopy (cryo-SEM) as a tool for studying the
      ultrastructure during bead formation by ionotropic gelation of calcium pectinate.
AB  - Understanding the gel ultrastructure is of great importance for process and
      product development having great effects on the product characteristics. The
      samples containing high amount of water could not be directly observed using
      scanning electron microscope (SEM) without removing of water. However, cryo-SEM
      can be used to study the ultrastructure of hydrated samples. In this study,
      ultrastructural information of internal structure was obtained by imaging the
      cryo-fractured beads in a cryo-SEM. This technique was found to be excellent for
      studying the detailed morphology of structural development and showed better
      images than normal SEM procedures using freeze-drying for sample preparation.
      Also, the studies illustrated a morphological change, e.g. from net-like
      structure to membranous structure caused by syneresis, accompanied by a
      significant increase in mechanical properties, when the beads are formed by
      ionotropic gelation. The gelation time of 20 min was found to be the minimum for
      a complete bead formation, based on the mechanical and SEM data. The results
      demonstrate the advantageous of cryo-SEM for examining the ultrastructure during
      bead formation of calcium pectinate.

PMID- 18054455
TI  - Development of a simple and non-destructive examination for counterfeit coins
      using acoustic characteristics.
AB  - The measurement of the sound by the shock wave and the analysis of the natural
      frequencies were carried out for the authentic and five kinds of counterfeit 500
      yen coins for the purpose of the quick and simple discrimination. Four peaks of
      natural frequencies were observed in the range of 5-20 kHz for authentic coins.
      On the other hand, only three peaks were observed for some kinds of the
      counterfeit coins. Four peaks were observed for other counterfeit coins, however
      the peaks were slightly shifted compared to those for authentic coins. These
      results show that the discrimination of the counterfeit coins from authentic ones
      can be realized by the examination of the natural frequencies. This method is
      quite useful for the simple screening of authentic and counterfeit coins.

PMID- 18054454
TI  - Herbal medicines used in the treatment of malaria in Budiope county, Uganda.
AB  - AIM OF THE STUDY: This study was conducted to document herbal medicines (HMs)
      used in the treatment of malaria as well as the existing knowledge, attitudes and
      practices related to malaria recognition, control and treatment in Budiope
      county, Uganda. METHODS: Data was collected using semi-structured interviews, and
      open- and close-ended questionnaires. RESULTS: The respondents had a good
      understanding of malaria, and could recognize it and distinguish it from other
      fever types. They were also aware that malaria was spread by mosquitoes. Malaria
      prevalence was high, and affected individuals an average of six times a year.
      Respondents avoided mosquito bites by using mosquito nets, clearing bush around
      their homesteads, and burning plant parts to generate smoke. They preferred
      treating malaria using allopathic medicines because, according to them, they
      lacked the appropriate traditional knowledge necessary to exploit plants for the
      treatment of malaria. Secondly, allopathic medicines were believed to be superior
      to HMs in the treatment of malaria. Twenty-seven species were used for the
      treatment of malaria. The most frequently mentioned were Vernonia amygdalina,
      Momordica foetida, Zanthoxylum chalybeum, Lantana camara and Mangifera indica.
      Drugs from these plants were prepared from single species as water extracts and
      were administered in variable doses over varied time periods.

PMID- 18054456
TI  - Congenital malformations of the external and middle ear.
AB  - With the focus on imaging, this paper gives a summarized view of the present
      knowledge on fields, which are necessary to know for a profound understanding of
      congenital malformations of the external and middle ear. Typical and less typical
      combinations of malformed parts of the ear can be derived from the embryogenesis.
      Clinical signs and audiometric findings lead to diagnosis in congenital aural
      atresia. Isolated middle ear malformations can be clinically mixed up especially
      with otosclerosis and tympanosclerosis. Imaging is needed for exact morphological
      information. In malformations of the external and middle ear, CT is the imaging
      modality of choice. Requirements on CT-technique as well as radiological findings
      including classification and pre-surgical rating are described. Morphological CT
      correlates of congenital malformations and their differential diagnoses are
      enlisted and illustrated. The impact of CT-results on therapy is explained and
      actual therapeutic concepts are briefly presented.

PMID- 18054457
TI  - Quantitation of acetol in common pharmaceutical excipients using LC-MS.
AB  - A method for the quantification of acetol at mug/L levels in propylene glycol and
      glycerol, two common pharmaceutical excipients, was developed and validated. This
      simple yet highly specific method makes use of derivatization by O-(2,3,4,5,6
      pentafluorobenzyl)hydroxylamine (PFBHA) in aqueous solution at room temperature
      followed by analysis via LC-MS without sample pre-concentration, extraction, or
      cleanup. Kinetic studies indicated that the derivatization reaction was complete
      after 4.5h. Preliminary investigations demonstrate the applicability of this
      method to the separation and identification of other electrophilic impurities.
      This suggests the potential for a simple, quantitative assay at room temperature
      in aqueous solution for the determination of a variety of electrophilic
      impurities in pharmaceutical excipients, without the need for sample
      concentration or extraction.

PMID- 18054458
TI  - Surface analysis of new chlorpromazinium plastic membrane electrodes.
AB  - New chlorpromazinium (Cp) plastic membrane electrodes of the conventional type
      were constructed and characterized. They are based on incorporation of Cp
      reineckate (CpRn) ion pair, Cp-phosphotungstate (Cp3PT), or Cp-phosphomolybdate
      (Cp3PM) ion associate into poly(vinyl chloride) membrane. The electrodes
      exhibited calibration graph slopes of 49.83, 52.87, and 61.30 mV/Cp concentration
      decade over life spans of 1, 5, and 3 days, respectively. All electrodes proved
      to be selective for Cp and have been applied to the assay of a pharmaceutical
      preparation. Energy dispersive spectroscopy (EDS) and X-ray photoelectron
      spectroscopy (XPS), as well as scanning electron microscopy (SEM) showed that the
      limitation of the lifetime of the electrodes is attributed to leaching of the ion
      exchanger from the membrane into the test solution in addition to deformation of
      the surface.

PMID- 18054459
TI  - Development and validation of a rapid RP-HPLC method for the determination of
      cetirizine or fexofenadine with pseudoephedrine in binary pharmaceutical dosage
      forms.
AB  - The objective of the current study was to develop a simple, accurate, precise and
      rapid reversed-phase HPLC method and subsequent validation using ICH suggested
      approach for the determination of antihistaminic-decongestant pharmaceutical
      dosage forms containing binary mixtures of pseudoephedrine hydrochloride (PSE)
      with fexofenadine hydrochloride (FEX) or cetirizine dihydrochloride (CET). The
      chromatographic separation of PSE, FEX and CET was achieved on a Zorbax C8 (150
      mm x 4.6mm; 5 microm particle size) column using UV detection at 218 and 222 nm.
      The optimized mobile phase was consisted of TEA solution (0.5%, pH 4.5)-methanol
      acetonitrile (50:20:30, v/v/v). The retention times were 1.099, 2.714 and 3.808
      min for PSE, FEX and CET, respectively. The proposed method provided linear
      responses within the concentration ranges 30-240 and 1.25-10 microg ml(-1) with
      LOD values of 1.75 and 0.10 microg ml(-1) for PSE and CET, respectively.
      Linearity range for PSE-FEX binary mixtures were 10-80 and 5-40 microg ml(-1)
      with LOD values of 0.75 and 0.27 microg ml(-1) for PSE and FEX, respectively.
      Correlation coefficients (r) of the regression equations were greater than 0.999
      in all cases. The precision of the method was demonstrated using intra- and inter
      day assay R.S.D. values which were less than 1% in all instances. No interference
      from any components of pharmaceutical dosage forms or degradation products was
      observed. According to the validation results, the proposed method was found to
      be specific, accurate, precise and could be applied to the quantitative analysis
      of these drugs in capsules containing PSE-CET or extended-release tablets
      containing PSE-FEX binary mixtures.

PMID- 18054460
TI  - Cyclic tensile strain increases interactions between human epidermal
      keratinocytes and quantum dot nanoparticles.
AB  - The effects of quantum dots (QD) on cell viability have gained increasing
      interest due to many recent developments utilizing QD for pharmaceutical and
      biomedical applications. The potential use of QD nanoparticles as diagnostic,
      imaging, and drug delivery agents has raised questions about their potential for
      cytotoxicity. The objective of this study was to investigate the effects of
      applied strain on QD uptake by human epidermal keratinocytes (HEK). It was
      hypothesized that introduction of a 10% average strain to cell cultures would
      increase QD uptake. HEK were seeded at a density of 150,000 cells/mL on collagen
      coated Flexcell culture plates (Flexcell Intl.). QD were introduced at a
      concentration of 3 nM and a 10% average strain was applied to the cells. After 4h
      of cyclic strain, the cells were examined for cell viability, QD uptake, and
      cytokine production. The results indicate that addition of strain results in an
      increase in cytokine production and QD uptake, resulting in irritation and a
      negative impact on cell viability. Application of physiological load conditions
      can increase cell membrane permeability, thereby increasing the concentration of
      QD nanoparticles in cells.

PMID- 18054461
TI  - Acute deviations from long-term trait depressive symptoms predict systemic
      inflammatory activity.
AB  - OBJECTIVE: Depressive symptoms increase morbidity and mortality from coronary
      heart disease and systemic inflammation has been proposed as the underlying
      mechanism. While higher levels of inflammatory mediators have been found in
      dysphoric individuals, it is not known whether long-term or short-term mood
      changes are responsible for this phenomenon. METHODS: A sample of 65 young women
      provided weekly web-based self-ratings of depressive mood over a period of 20
      weeks using the CES-D, and systemic inflammation was assessed by measuring plasma
      interleukin-6 (IL-6) and C-reactive protein (CRP) before and after the
      observation period. CES-D ratings were used to develop state and trait indicators
      of depressed mood and evaluate their relationship with inflammatory mediators.
      RESULTS: Hierarchical linear regressions controlling for baseline inflammation,
      age, and BMI revealed that trait levels of depressive symptoms were not
      associated with IL-6 (beta=0.09; n.s.) and CRP (beta=0.01; n.s.) concentrations
      after the observation period. In contrast, state levels of depressive symptoms
      were associated with changes in IL-6, but not CRP, particularly when they were
      indexed as the disparity between a person's trait level of symptoms and her CES-D
      score just prior to IL-6 assessment (beta=0.35; p=0.03). CONCLUSION: These
      results lead us to conclude that in young women, state, rather than trait
      depressed mood stimulates peripheral inflammation as measured by IL-6. This
      pattern suggests that in this age group, fast-reacting inflammatory mediators
      such as IL-6 probably respond to short-term changes, for example, in stress
      hormones or stress hormone sensitivity, rather than long-term dysregulations of
      allostatic mechanisms.

PMID- 18054462
TI  - Seizure activity and changes in hippocampal extracellular glutamate, GABA,
      dopamine and serotonin.
AB  - Increases in hippocampal extracellular neurotransmitter levels have consistently
      been observed during temporal lobe seizures in humans, but animal studies on this
      subject have yielded conflicting results. Our aim was to better characterise the
      relationship between seizure activity and changes in hippocampal glutamate, GABA,
      dopamine and serotonin by comparing three limbic seizure models which differ only
      in the pharmacological mechanism used to induce seizures. Seizures were evoked in
      freely moving rats by intrahippocampal microperfusion, via a microdialysis probe,
      of the muscarinic receptor agonist pilocarpine (10mM), GABA(A) receptor
      antagonist picrotoxin (100microM) or group I metabotropic glutamate receptor
      agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) (1mM). Seizure-related
      behavioural changes were scored and hippocampal extracellular glutamate, GABA,
      dopamine and serotonin concentrations were monitored. Seizures were of comparable
      severity in all groups. During seizures, hippocampal glutamate, GABA and dopamine
      concentrations increased in all groups. Glutamate increases were significantly
      higher in the picrotoxin group. Hippocampal serotonin concentration increased
      following pilocarpine and picrotoxin, but not DHPG. Our results suggest a direct
      relationship between seizure activity and increased hippocampal extracellular
      concentrations of glutamate, GABA and dopamine, but not serotonin. The fact that
      picrotoxin induces seizures by disinhibition, rather than direct excitation, may
      account for the larger glutamate increases in this group.

PMID- 18054463
TI  - Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor increases
      pentylenetetrazol seizure threshold in mice: possible involvement of
      adenosinergic mechanism.
AB  - Multiple lines of investigations have explored the role of cyclooxygenases (COX)
      in epilepsy and related neuropsychiatric disorders. Cyclooxygenase particularly,
      COX-2 expression was found to increase in brain during seizure paradigms. The
      present study was carried out to investigate the effect of rofecoxib, a selective
      COX-2 inhibitor against pentylenetetrazol (PTZ i.v.) seizure threshold in mice.
      The study was further extended to elucidate the possible involvement of
      adenosinergic mechanism in mediating its anticonvulsant action. Minimal dose of
      PTZ (i.v., mg/kg) needed to induce different phases (myoclonic jerks, generalized
      clonus and tonic extension) of PTZ convulsions were noted as an index of seizure
      threshold. Acute administration of rofecoxib (4mg/kg, i.p.) before PTZ infusion
      produced an elevation of seizure threshold for all the phases of convulsions. A
      lower dose of rofecoxib (2mg/kg, i.p.) showed an increase in PTZ seizure
      threshold for the onset of myoclonic jerks and tonic extension phases but not for
      generalized clonus. A still lower dose of rofecoxib (1mg/kg, i.p.) failed to
      increase the threshold in any of the convulsive phases induced by PTZ i.v.
      infusion. Pretreatment with sub-effective dose of rofecoxib (1mg/kg, i.p.)
      enhanced the action of sub-protective doses of either adenosine (25mg/kg, i.p.)
      or 2-chloroadenosine (1 or 2mg/kg, i.p.) in increasing the seizure threshold. On
      the contrary, treatment with caffeine (100 or 200mg/kg, i.p.) or theophylline (50
      or 100mg/kg, i.p.), both non-selective A(1)/A(2) adenosine receptor antagonists
      reversed the anticonvulsant effect of rofecoxib (4mg/kg, i.p.). Further,
      dipyridamole (5mg/kg, i.p.), an adenosine uptake inhibitor displayed an
      anticonvulsant effect with rofecoxib (1mg/kg, i.p.). The study for the first time
      demonstrated the possible involvement of adenosinergic system in the
      anticonvulsant effects of rofecoxib against PTZ i.v. seizure threshold paradigm
      in mice.

PMID- 18054465
TI  - Concentrations of moxifloxacin in plasma and urine, and penetration into
      prostatic fluid and ejaculate, following single oral administration of 400 mg to
      healthy volunteers.
AB  - The spectrum of chronic bacterial prostatitis (CBP) comprises Gram-negative, Gram
      positive and atypical pathogens. Because of its broad spectrum of activity,
      moxifloxacin might be a suitable antibiotic for the treatment of CBP. In this
      pharmacokinetic study, plasma concentrations and the penetration of moxifloxacin
      into prostatic fluid and ejaculate were investigated. Twelve healthy male
      volunteers received a single oral dose of 400mg moxifloxacin and at the same time
      received 3.24 g of iohexol intravenously to assess urinary contamination of
      prostatic fluid and ejaculate. Plasma concentrations were determined at 0, 0.5,
      1, 2, 3 and 4h and prostatic fluid and ejaculate (mean+/-standard deviation
      (S.D.)) were determined at 3.5+/-0.4h and 3.6+/-0.4h, respectively, following
      administration of drugs. Urinary concentrations were determined in the urine
      collected from 0-4.5h. Concentrations of moxifloxacin and iohexol in plasma,
      secretions and urine were determined by high-performance liquid chromatography.
      The mean+/-S.D. peak plasma concentration of moxifloxacin was 2.8+/-0.5 mg/L
      observed after 1.6+/-0.9h. In prostatic fluid, the concentration of moxifloxacin
      was 3.8+/-1.2 mg/L and the prostatic fluid/plasma ratio was 1.6+/-0.5. In
      ejaculate, the concentration was 2.5+/-0.7 mg/L and the ejaculate/plasma ratio
      was 1.0+/-0.2. Moxifloxacin concentrations in prostatic fluid were ca. 60%
      (P<0.05) higher than in plasma and concentrations in ejaculate were approximately
      the same as in plasma. Therefore, moxifloxacin might be a good alternative for
      the treatment of CBP, but further studies are warranted to establish this
      indication.

PMID- 18054466
TI  - Withdrawal of growth-promoting antibiotics: comments on Commentary.

PMID- 18054467
TI  - Urinary tract infections in patients with diabetes mellitus: epidemiology,
      pathogenesis and treatment.
AB  - Patients with diabetes mellitus (DM) have a higher prevalence of asymptomatic
      bacteriuria (ASB) and incidence of urinary tract infections (UTIs) compared with
      patients without DM. They also more often have bacteraemia, with the urinary
      tract as the most common focus for these infections, as well as a higher
      mortality outside the hospital compared with patients without DM. It appears that
      the increased prevalence of ASB in diabetic women is not the result of a
      difference in causative bacteria, as the same virulence factors and resistance to
      antimicrobials were found in Escherichia coli isolated from the urine of diabetic
      women with ASB compared with non-diabetic controls. Bacterial growth in vitro is
      increased after the addition of glucose, however glucosuria is not a risk factor
      for ASB or for the development of UTIs in vivo. No differences in granulocyte
      function tests were demonstrated among diabetic women with ASB, non-bacteriuric
      women and healthy control subjects, but women with both ASB and DM had lower
      urinary cytokine and leukocyte concentrations than women with ASB without DM.
      Finally, it was found that E. coli expressing type 1 fimbriae adhere better to
      uroepithelial cells of women with DM compared with those isolated from women
      without DM. There are no randomised trials that answer the question as to the
      optimal duration of treatment for UTIs in diabetic patients. It has been
      recommended to consider these patients as having a complicated UTI and therefore
      to treat them for a period of 7-14 days.

PMID- 18054468
TI  - Activities of fluconazole and voriconazole against bloodstream isolates of
      Candida glabrata and Candida krusei: a 14-year study in a Spanish tertiary
      medical centre.
AB  - The aim of this study was to evaluate the in vitro activities of voriconazole and
      fluconazole against Candida glabrata and Candida krusei isolated from blood
      during a 14-year period (1990-2003) at the tertiary care hospital of Cruces
      (Barakaldo, Spain). The in vitro activities of fluconazole and voriconazole
      against 28 isolates of C. glabrata and 15 isolates of C. krusei were determined
      by the Clinical and Laboratory Standards Institute disk diffusion method. Of the
      28 C. glabrata isolates tested, 24 (85.7%) were susceptible (S) to fluconazole, 2
      (7.1%) were susceptible dose-dependent (S-DD) and 2 (7.1%) were resistant (R).
      All C. krusei isolates were classified as R to fluconazole. Resistance to
      voriconazole was observed in one isolate each of C. glabrata (3.6%) and C. krusei
      (6.7%), and one isolate of each species was S-DD. These results were confirmed by
      the Sensititre YeastOne and Etest methods, with good comparative results.
      Voriconazole was very active in vitro against C. glabrata and C. krusei blood
      isolates and the resistance observed was not related to the introduction of
      voriconazole in the therapeutic schedule of the hospital. These facts support the
      usefulness of voriconazole as a therapeutic tool for candidaemia caused by these
      species.

PMID- 18054469
TI  - In vitro interactions of antifungal agents against clinical isolates of Fusarium
      spp.
AB  - The in vitro activities of amphotericin B (AMB), itraconazole (ITC), voriconazole
      (VCZ) and terbinafine (TBF) alone and in the combinations AMB+VCZ, TBF+ITC and
      TBF+VCZ were evaluated against 29 clinical isolates of Fusarium spp. (15 Fusarium
      solani, 7 Fusarium oxysporum, 2 Fusarium decemcellulare, 2 Fusarium dimerum and 3
      other Fusarium spp.). Minimum inhibitory concentrations were determined using the
      method of the Clinical and Laboratory Standards Institute and the interaction
      activity was calculated using the fractional inhibitory concentration index. The
      four antifungal drugs tested alone showed very limited activity against most of
      the isolates. In contrast, the combination TBF+VCZ showed synergy for 21
      isolates. The combination AMB+VCZ showed synergism for only five strains. No
      interaction or antagonism was observed among the remaining strains. TBF+ITC
      showed no interaction for 18 strains. The in vitro antifungal activity of the
      drugs alone and in combination varied for different species. These results
      corroborate previous in vitro studies in which the combination TBF+VCZ showed
      synergy against Fusarium spp., although further studies are needed to elucidate
      its potential usefulness for therapy.

PMID- 18054471
TI  - A comparison of treatment planning techniques used in two randomised UK external
      beam radiotherapy trials for localised prostate cancer.
AB  - AIMS: To compare the radiotherapy planning techniques from two multicentre
      randomised external beam radiotherapy trials in the UK of conformal radiotherapy
      vs intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Sixteen
      sequential patients with histologically confirmed localised prostate cancer
      treated in the conventional or hypofractionated IMRT trial (CHHiP) were planned
      using both the CHHiP and Medical Research Council RT-01 planning protocols to 74
      Gy in 37 daily fractions. The CHHiP plan used a single phase simple forward
      planned three-field IMRT plan for easy multicentre adoption. The RT-01 plan used
      two phases: three-field conformal radiotherapy plan to 64 Gy followed by a six
      field boost of 10 Gy. After coverage of the planning target volumes according to
      the respective trial protocols, the dose to the rectum and bladder was assessed
      for the two planning techniques. RESULTS: There was acceptable planning target
      volume coverage by both the CHHiP and RT-01 plans. All CHHiP plans produced lower
      mean irradiated rectal volumes at all measured dose levels compared with the RT
      01 plans, particularly for irradiated rectal volumes at 50 and 70 Gy (P<0.05). In
      the cases when a CHHiP plan failed to meet its own trial dose constraints, the
      volumes of irradiated rectum were less than if an RT-01 planning technique had
      been used. The CHHiP plans gave lower mean irradiated bladder volumes at both 50
      and 60 Gy, but higher volumes at 74 Gy. These differences in irradiated bladder
      volumes were significant at the 60 and 74 Gy dose levels (P<0.05) in favour of
      the CHHiP and RT-01 plans, respectively. CONCLUSION: The forward planned CHHiP
      IMRT planning solution gives more favourable rectal sparing than the RT-01 plan.
      This is important to limit any potential increase in late rectal toxicity for
      prostate cancer patients treated with high-dose conventional or hypofractionated
      schedules.

PMID- 18054470
TI  - Subsets of cloned mouse embryos and their non-random relationship to development
      and nuclear reprogramming.
AB  - An important question in oocyte-mediated nuclear reprogramming is whether gene
      expression of the donor nucleus changes randomly or follows a pattern. Since
      cloned embryos are very heterogeneous and arrest frequently during
      preimplantation development, a random scenario is generally accepted. In the
      present study, we resolve the heterogeneity of cumulus cell-derived mouse clones
      by recognizing structured subsets, and we analyze their relationship to
      reprogramming of donor nuclei. We utilize live cell imaging of the Oct4 promoter
      driven GFP transgene to resolve the populations of cloned and ICSI-fertilized
      morulae, and we sort them both into three subsets based on different GFP
      expression. Functionally, subsets of cloned but not ICSI morulae form blastocysts
      and ES cells proportional to Oct4-GFP expression. Regulatively, the subsets of
      cloned morulae are characterized by small differences of transcript level for the
      pluripotency-associated genes Oct4, Nanog and Sox2. Small differences of the
      level of select mRNAs across subsets suggest a uniform rather than random course
      of reprogramming from the morula stage on. Since these small differences
      correspond with substantial differences in developmental competence, we propose
      that developmental potential of clones relates to levels of gene expression in a
      different way than fertilized embryos.

PMID- 18054472
TI  - Acetaminophen-induced liver damage in mice: effects of some medicinal plants on
      the oxidative defense system.
AB  - Paracetamol (acetaminophen, PCM) is widely used as an over-the-counter analgesic
      and antipyretic drug. Intake of a large dose of PCM may result in severe hepatic
      necrosis. Oxidative stress mediated by oxidative capacities of the PCM metabolite
      (N-acetyl-p-benzoquinoneimine (NAPQI), is considered as the main cause of
      hepatotoxicity of PCM. This work therefore seeks to induce liver damage in mice
      using single dose (25 0mg/kg) of acetaminophen and to evaluate the possible
      protective effects of administration (100mg/kg) of some medicinal plants (Kigelia
      africana, Calotropis procera, Hibiscus sabdariffa and Alchornea cordifolia) on
      PCM-induced liver damage in mice. The alanine aminotransferase (ALT), and
      aspartate aminotransferase (AST) activities were determined in the plasma of
      mice. Equally, comparative effects of these plants on lipid peroxidation product
      thiobarbituric reacting substances (TBARS) and some antioxidant enzymes
      superoxide dismutase (SOD), catalase (CAT), gluthathione peroxidase (GPx), and
      delta-aminolevulinate dehydratase (delta-ALA-D) activities, were also evaluated
      in the mouse liver homogenate. Paracetamol caused liver damage as evident by
      statistically significant (P<0.05) increased in plasma activities of AST and ALT.
      There were general statistically significant losses in the activities of SOD,
      GPx, CAT, and delta-ALA-D and an increase in TBARS in the liver of paracetamol
      treated group compared with the control group. However, all the tested plants
      except Calotropis procera were able to counteract these effects. The present
      results suggest that these plants can act as hepatoprotectives against
      paracetamol toxicity and that the mechanism by which they do this is by acting as
      antioxidants.

PMID- 18054474
TI  - Comparative study of Rhodiola preparations on behavioral despair of rats.
AB  - The antidepressant-like activity of an extract of the roots of Rhodiola rosea
      (RR), its combination with piperine containing extract (RPE), pure substances
      isolated from Rhodiola, such as rhodioloside, rosavin, rosin, rosarin, tyrosol,
      cinnamic alcohol, cinnamaldehyde and cinnamic acid has been assessed in
      laboratory animals through application of the Porsolt behavioural despair assay.
      RR increased the swimming time of rats in a dose dependent manner (ED50=7 mg/kg)
      and, when administered at 20mg/kg, exhibited a stronger anti-depressant type
      effect than either imipramine (at 30 mg/kg) or an extract of Hypericum perforatum
      (at 20mg/kg). Rhodioloside, and tyrosol were identified as active principles of
      the extract, whereas rosavin, rosarin, rosin, cinnamic alcohol, cinnamaldehyde,
      cinnamic acid were inactive. A fixed combination of rhodioloside, rosavin,
      rosarin and rosin was more active than any of the individual components alone,
      indicating a synergistic effect of the ingredients in RR extract. Piperine in
      combination with Rhodiola (RPE) distorts pharmacological effect of Rhodiola most
      probably due to changes of pharmacokinetic profile of rhodioloside and rosavin.
      RPE cannot provide predictable therapeutic effect due to herb-herb interaction.
      Moreover, concomitant treatment of RPE with other drugs should also be excluded
      due to drug-piperine interaction.

PMID- 18054475
TI  - Rationale for adjuvant fatty acid therapy to prevent radiotherapy failure and
      tumor recurrence during early laryngeal squamous cell carcinoma.
AB  - Information from a preceding lipid study contributed to the pathobiological
      assessment of laryngeal squamous cell carcinoma (LSCC). Lipid-driven signaling
      pathways are responsible for laryngeal carcinogenesis and immunodeficiency. The
      construction of fatty acid (FA) profiles for LSCC allowed the identification of
      FA role players. The integration of lipid and clinicomolecular information
      encountered in the literature, in turn, allowed the identification of biological
      prognostic markers to distinguish between early (less aggressive) and advanced
      (more aggressive) LSCCs. High arachidonic acid (AA) and cyclooxygenase (COX-2)
      activities are criteria for less aggressive growth, whilst low AA and COX-2
      activities occur during more aggressive growth. Excessive tobacco use and
      environmental smoke or human papillomavirus (HPV) infection and alcohol abuse
      can, respectively, elicit cumulative oxidative stress and an oxidative burst or
      interfere with signaling pathways during essential fatty acid (EFA) metabolism,
      all factors and events which may cause LSCC. Research revealed that enhanced COX
      2 activity and Bcl-2 expression prevent apoptosis and, hence, LSCCs become
      resistant to radiotherapy. It was also observed that recurrent laryngeal cancers
      become more aggressive after radiotherapy failure. It is predicted that
      manipulation of AA activity and consequently a cascade of downstream factors that
      include COX-2 and Bcl-2 expression responsible for LSCC may have therapeutic
      potential to improve radiotherapy outcome during early LSCC. Adjuvant FA therapy
      to improve early LSCC management by counteracting radiotherapy failure and
      unwanted complications for further management is proposed. FA therapeutic
      strategies before and during radiotherapeutic courses need to be evaluated.

PMID- 18054476
TI  - Municipal solid waste characteristics and management in Gumushane, Turkey.
AB  - This paper presents a general overview of the current municipal solid waste (MSW)
      management in Gumushane Province, Turkey. In order to characterize the solid
      waste stream in the Municipality of Gumushane, a long-term study was conducted
      over a 52-week period between the spring of 2004 and the winter of 2005. In this
      study, percentage of components and specific weight of the MSW, the composting
      parameters (moisture content, total organic carbon, total nitrogen and pH),
      organic matter content, calorific value and the heavy metal concentrations (Cd,
      Cr, Cu, Ni, Pb, Zn, Fe, Mn, Co) of the compostable wastes sorted from the mixed
      MSW were determined and evaluated. In Gumushane, a mean of 70 tons of MSW are
      generated each day or 1 kg/day/capita. Approximately 4,500 kg of the MSW were
      collected and sorted in a year, and the mean specific weight of these is 308
      kg/m(3). Approximately 30% of the MSW generated is compostable wastes and the
      yearly mean moisture content, organic matter content, C/N ratio and pH of these
      are 78%, 92.1%, 21.6/1 and 4.73, respectively, and approximately 24% of the MSW
      consists of recyclable materials. The recommended system deals with maximizing
      recycling and minimizing landfilling of the MSW, and consists of separation at
      source, collection, sorting, recycling, composting and sanitary landfilling.
      Heavy metal concentrations of the compostable wastes from the open dump were
      determined to decrease in the following order: Fe>Mn>Zn>Cr>Cu>Pb>Ni>Cd>Co.

PMID- 18054477
TI  - Redox and ion-exchange properties in surface-tethered DNA-conducting polymers.
AB  - A poly(cyclopentadithiophene) matrix modified by DNA covalently fixed to the
      surface has been designed to study the redox and ion-exchange properties in
      surface-tethered DNA-conducting polymers. Voltammetric investigations show an
      improvement in conductivity, originating from DNA modification, probably due to
      changes in charged-density and size of dopant species. Cyclic voltammetry with
      concomitant QCM measurements indicate that the mass changes are consistent with
      an ejection of Na(+) cations associated to the anionic phosphate groups,
      attesting a DNA contribution to the p-doping process. So, in contrast to the
      classic doping patterns, the p-doping process of surface-tethered DNA-copolymer
      exhibits a cation-controlled transport mechanism. Impedimetric investigations
      indicate that for long enough DNA target sequence, nucleic acid preserves certain
      flexibility and is involved in the p-doping process through a diffusion-like
      motion. These results give new opportunities for genesensors development and for
      a better understanding of bioactive conducting surfaces.

PMID- 18054478
TI  - Detection of DNA hybridization and extension reactions by an extended-gate field
      effect transistor: characterizations of immobilized DNA-probes and role of
      applying a superimposed high-frequency voltage onto a reference electrode.
AB  - As we have already shown in a previous publication [Kamahori, M., Ihige, Y.,
      Shimoda, M., 2007. Anal. Sci. 23, 75-79], an extended-gate field-effect
      transistor (FET) sensor with a gold electrode, on which both DNA probes and 6
      hydroxyl-1-hexanethiol (6-HHT) molecules are immobilized, can detect DNA
      hybridization and extension reactions by applying a superimposed high-frequency
      voltage to a reference electrode. However, kinetic parameters such as the
      dissociation constant (K(d)(s)) and the apparent DNA-probe concentration
      (C(probe)(s)) on a surface were not clarified. In addition, the role of applying
      the superimposed high-frequency voltage was not considered in detail. In this
      study, the values of K(d)(s) and C(probe)(s) were estimated using a method
      involving single-base extension reaction combined with bioluminescence detection.
      The value of K(d)(s) on the surface was 0.38 microM, which was about six times
      that in a liquid phase. The value of C(probe)(s), which expressed the upper
      detection limit for the solid phase reaction, was 0.079 microM at a DNA-probe
      density of 2.6 x 10(12)molecules/cm(2). We found that applying the superimposed
      high-frequency voltage accelerated the DNA molecules to reach the gold surface.
      Also, the distance between the DNA-probes immobilized on the gold surface was
      controlled to be over 6 nm by applying a method of competitive reaction with DNA
      probes and 6-HHT molecules. This space was sufficient to enable the immobilized
      DNA-probes to lie down on the 6-HHT monolayer in the space between them. Thus,
      the FET sensor could detect DNA hybridization and extension reactions by applying
      a superimposed high-frequency voltage to the DNA-probes density-controlling gold
      surface.

PMID- 18054479
TI  - Glucose biosensor based on electrodeposition of platinum nanoparticles onto
      carbon nanotubes and immobilizing enzyme with chitosan-SiO(2) sol-gel.
AB  - A novel amperometric biosensor, based on electrodeposition of platinum
      nanoparticles onto multi-walled carbon nanotube (MWNTs) and immobilizing enzyme
      with chitosan-SiO(2) sol-gel, is presented in this article. MWNTs were cast on
      the glass carbon (GC) substrate directly. An extra Nafion coating was used to
      eliminate common interferents such as acetaminophen and ascorbic acids. The
      morphologies and electrochemical performance of the modified electrodes have been
      investigated by scanning electron microscopy (SEM) and amperometric methods,
      respectively. The synergistic action of Pt and MWNTs and the biocompatibility of
      chitosan-SiO(2) sol-gel made the biosensor have excellent electrocatalytic
      activity and high stability. The resulting biosensor exhibits good response
      performance to glucose with a wide linear range from 1 microM to 23 mM and a low
      detection limit 1 microM. The biosensor also shows a short response time (within
      5s), and a high sensitivity (58.9 microAm M(-1)cm(-2)). In addition, effects of
      pH value, applied potential, rotating rate, electrode construction and
      electroactive interferents on the amperometric response of the sensor were
      investigated and discussed in detail.

PMID- 18054480
TI  - Near real-time detection of Cryptosporidium parvum oocyst by IgM-functionalized
      piezoelectric-excited millimeter-sized cantilever biosensor.
AB  - Piezoelectric-excited millimeter-sized cantilever (PEMC) biosensors were
      fabricated and functionalized with immunoglobulin M (IgM) for the detection of
      Cryptosporidium parvum oocyst in a flow configuration at 1 mL/min. The detection
      of 100, 1000, and 10,000 oocysts/mL was achieved with a positive sensor response
      in less than 1 min. Bovine serum albumin (BSA) was used as a blocking agent in
      each experiment and was shown to eliminate non-specific binding. The sensor's
      resonance frequency response correlates with C. parvum oocyst concentration
      logarithmically. The oocyst attachment rate was found to increase by an order of
      magnitude in increasing concentration from 100 to 10,000 oocysts/mL. The
      significance of these results is that IgM-functionalized PEMC sensors are highly
      selective and sensitive to C. parvum oocyst and therefore, have the potential to
      accurately identify and quantify C. parvum oocyst in drinking water.

PMID- 18054481
TI  - Rapid detection of influenza A virus in clinical samples using an ion channel
      switch biosensor.
AB  - This report describes the fabrication and successful use of the ion channel
      switch biosensor (ICSB) for rapid point-of-care detection of influenza A in
      different types of respiratory specimens. Virus culture -- regarded as the "gold
      standard" -- and an immunochromatographic rapid point-of-care test for influenza
      A virus were compared with the biosensor. The ICSB rapid test provided an
      objective readout within 10 min of specimen inoculation into the ICSB chamber
      wells, without the need for chemical or other pretreatments. Construction of the
      ICSB with specific antibodies also enables rapid detection and identification of
      appropriate influenza A subtypes.

PMID- 18054482
TI  - Direct electrochemistry and electrocatalysis of horseradish peroxidase based on
      clay-chitosan-gold nanoparticle nanocomposite.
AB  - Gold nanoparticles stabilized by chitosan (AuCS) were hybridized with exfoliated
      clay nanoplates through electrostatic interaction. The resulting clay-chitosan
      gold nanoparticle nanocomposite (Clay/AuCS) was used to modify glassy carbon
      electrode (GCE). HRP, a model peroxidase, was entrapped between the Clay/AuCS
      film and another clay layer. UV-vis spectrum suggested HRP retained its native
      conformation in the modified film. Basal plane spacing of clay obtained by X-ray
      diffraction (XRD) indicated that there was an intercalation-exfoliation
      restacking process among HRP, AuCS and clay during the modified film drying. The
      immobilized HRP showed a pair of quasi-reversible redox peaks at -0.195 V (vs.
      saturated Ag/AgCl electrode) in 0.1M PBS (pH 7.0), and the biosensor displayed a
      fast amperometric response to H(2)O(2) with a wide linear range of 39 microM to
      3.1 mM. The detection limit was 9.0 microM based on the signal to noise ratio of
      3. The kinetic parameters such as alpha (charge transfer coefficient), k(s)
      (electron transfer rate constant) and K(m) (Michaelis-Menten constant) were
      evaluated to be 0.53, 2.95+/-0.20s(-1) and 23.15 mM, respectively.

PMID- 18054483
TI  - What happens after the learning curve? A single surgeon's experience of 412
      laparoscopic left colectomies and rectal resections.

PMID- 18054484
TI  - Bioactivity of two major constituents isolated from the essential oil of
      Artemisia judaica L.
AB  - The essential oil of Artemisia judaica L., grown on Sinai Peninsula of Egypt, was
      extracted via hydrodistillation. Chromatographic separation on repeated silica
      gel columns led to isolate two compounds namely piperitone and trans-ethyl
      cinnamate. Insecticidal, antifeedant and antifungal properties of the isolated
      compounds were examined. Both compounds showed pronounced insecticidal and
      antifeedant activity against the third instar larvae of Spodoptera littoralis
      (Boisd). trans-Ethyl cinnamate (LD(50)=0.37 microg/larva) was more toxic than
      piperitone (LD(50)=0.68microg/larva). The two isolated compounds revealed
      antifeedant activity in a concentration dependent manner, with complete feeding
      inhibition at a concentration of 1,000microg/ml. When tested for antifungal
      activity against four plant pathogenic fungi, the isolated compounds exhibited a
      moderate to high activity.

PMID- 18054485
TI  - Characterisation of Paenibacillus jamilae strains that produce exopolysaccharide
      during growth on and detoxification of olive mill wastewaters.
AB  - A total of 10 bacterial strains were isolated from a compost of corn treated with
      olive mill wastewaters (OMW) and selected by their capacity to synthesize
      exopolysaccharides (EPS). Morphological, physiological, biochemical and
      nutritional tests were used for a phenotypic study. A numerical analysis showed
      that all strains were 90% similar to each other. A DNA-DNA hybridization assay
      confirmed that all the strains belonged to Paenibacillus jamilae species. All the
      characterized strains were able to produce EPS growing on OMW batch cultures. The
      strain which was able to produce the highest EPS yield was chosen to perform an
      assay for testing its putative detoxifying activity, and it showed to reduce more
      than half the toxic capacity of the OMW. The results presented in this study,
      indicated the possible perspectives for using these bacterial strains to produce
      EPS and contribute to the bioremediation of the waste waters that are produced in
      the olive oil elaboration process.

PMID- 18054486
TI  - Polyphenol-enriched fractions from Sicilian grape pomace: HPLC-DAD analysis and
      antioxidant activity.
AB  - On the basis of a preliminary screening of seven different samples of Sicilian
      grape pomace, the 'Nerello Mascalese' sample NM2 was selected for an ethanol
      preparative extraction. The defatted NM2 EtOH extract was subjected to DPPH() and
      GAE assays, showing good radical scavenging activity (SC(50)=9.9 microg/mL) and a
      GAE value of 397.7 mg/g extract. HPLC-DAD analysis of NM2 extract allowed a
      quantitative determination of the main anthocyanins (AN) and flavonols/flavonol
      glycosides (FL/FG). Aliquots of the NM2 extract were subjected to three different
      fractionation protocols (FP1, FP2 and FP3). The fractions were examined by DPPH()
      and GAE assays, and subjected to HPLC-DAD analysis for the quantitative
      determination of the main AN and FL/FG. FP3 allowed obtaining a polyphenol
      enriched fraction with SC(50)=14.8 microg/mL and GAE=184.1mg/g of fraction,
      accounting for only 1.3% in weight of the EtOH extract. Some considerations about
      the relationship between antioxidant activity and AN/FL/FG HPLC-DAD profiles are
      also reported.

PMID- 18054487
TI  - Porphyrin conjugated to DNA by a 2'-amido-2'-deoxyuridine linkage.
AB  - A porphyrin that contains a single carboxylic acid group was synthesized and
      coupled to 2'-amino-2'-deoxyuridine. The resultant product contained a free 3'
      hydroxyl group and a 4,4'-dimethoxytrityl (DMT) protecting group on the 5'
      hydroxyl of the uridine, making it suitable for use in oligonucleotide synthesis.
      The 3' H-phosphonate derivative of this molecule was synthesized and used to form
      a conjugate with a 19 nucleotide sequence of DNA (5'-CCTCCAGTGGAAATCAAGG-3').
      This was carried out with the DNA attached at the 3' end to a control pore glass
      (CPG) substrate, allowing for rapid purification. After removal of the DMT group,
      an additional three nucleotides were added, leaving the porphyrin as an internal
      modification. This is the first report of porphyrin attached internally to an
      oligonucleotide using a hydrogen-bonding nucleoside analog. This allows
      oligonucleotides to be used as a scaffold for precise positioning of multiple
      porphyrins within biomimetic arrays.

PMID- 18054488
TI  - Novel thiol-based TACE inhibitors. Part 2: Rational design, synthesis, and SAR of
      thiol-containing aryl sulfones.
AB  - A series of potent thiol-containing aryl sulfone TACE inhibitors were designed
      and synthesized. The SAR and MMP selectivity of the series were investigated. In
      particular, compound 8b showed excellent in vitro potency against the isolated
      enzyme and good selectivity over MMP-2, -7, -8, -9, and -13. The X-ray structure
      of 8b in complex with TACE was also obtained.

PMID- 18054489
TI  - Novel heterocycle-substituted pyrimidines as inhibitors of NF-kappaB
      transcription regulation related to TNF-alpha cytokine release.
AB  - Novel heterocyclic ring-substituted pyrimidines have been designed as inhibitors
      of glycogen synthase kinase-3beta (GSK-3beta) from the modification of known
      inhibitors. Several potent inhibitors exhibiting nanomolar activities were
      discovered against GSK-3beta kinase as well as in an NF-kappaB reporter gene
      assay. Based on the results from in vitro TNF-alpha release inhibition and in
      vivo endotoxima, these inhibitors are expected to be useful candidates for
      treatment of inflammation-related diseases.

PMID- 18054490
TI  - Iromycins from Streptomyces sp. and from synthesis: new inhibitors of the
      mitochondrial electron transport chain.
AB  - Two new alpha-pyridone metabolites, iromycins E and F, were isolated from
      cultures of strain Streptomyces sp. Dra 17, thus expanding the recently
      discovered iromycin family. The inhibitory potential on the mitochondrial
      respiratory chain was examined and revealed that iromycin metabolites block NADH
      oxidation in beef heart submitochondrial particles with different efficacy, yet
      remarkably show only very low cytotoxicity. Difference spectroscopic studies
      indicated that iromycins inhibit the electron transport at the site of complex I
      (NADH-ubiquinone oxidoreductase). Derivatives of the natural products were
      semisynthetically prepared and provided detailed insights into structure-activity
      relationships. Drawn from these results, there are strong similarities with the
      piericidins, which are among the most potent complex I inhibitors of the
      mitochondrial electron transport chain. Furthermore, total synthesis afforded new
      analogues, and the non-natural iromycin S (IC50 = 58 ng/mL) emerged as the most
      active compound, thus opening avenues of future studies with the iromycins as new
      valuable biochemical tools.

PMID- 18054491
TI  - Activity of Mannich bases of 7-hydroxycoumarin against Flaviviridae.
AB  - Some Mannich bases of 7-hydroxycoumarin (2) and their simple derivatives (3 and
      4) were prepared and tested against viruses containing single-stranded, positive
      sense RNA genomes (ssRNA(+)). This study was directed toward Flaviviridae and, in
      particular, HCV surrogate viruses (BVDV, YFV). The 7-hydroxy derivatives 2 were
      generally devoid of activity, but when position 7 was propylated, the resulting 7
      propyloxy derivatives 3 were in some cases endowed with an interesting activity
      against BVDV. The formation of 7-benzoyl derivatives 4 gave compounds generally
      lacking in activity against Flaviviridae, whereas the appearance of activity
      against RSV has been observed. Also some unsymmetrical methylene derivatives 5-7
      (namely coumarins bridged to chromones or indoles) were found moderately active
      in antiviral tests. Derivatives 3 were submitted to a molecular modeling study
      using DNA polymerase of HCV as a target. The good correlation between calculated
      molecular modeling IC(50) and experimental EC(50) indicates that DNA polymerase
      is potentially involved in the inhibition of surrogate HCV viruses.

PMID- 18054492
TI  - Observation of long-range compositional fluctuations in glasses: implications for
      atomic and electronic structure.
AB  - Experimental evidence for long-range compositional fluctuations in glasses is
      given. The implications for electronic structure and stoichiometry-induced
      structural variations are analyzed. These fluctuations were discovered by
      examining the spatial dependence of inner shell near-edge absorption spectra
      obtained using a 50nm diameter probe. This spectroscopy is sensitive to both
      angular and distance correlations in bonding. Comparisons with spectra from
      compositionally equivalent crystals, and multiple-scattering calculations which
      include core-hole effects are used to analyze the data.

PMID- 18054493
TI  - Comparison of neutron and high-energy X-ray dual-beam radiography for air cargo
      inspection.
AB  - Dual-beam radiography techniques utilising various combinations of high-energy X
      rays and neutrons are attractive for screening bulk cargo for contraband such as
      narcotics and explosives. Dual-beam radiography is an important enhancement to
      conventional single-beam X-ray radiography systems in that it provides additional
      information on the composition of the object being imaged. By comparing the
      attenuations of transmitted dual high-energy beams, it is possible to build a 2D
      image, colour coded to indicate material. Only high-energy X-rays, gamma-rays and
      neutrons have the required penetration to screen cargo containers. This paper
      reviews recent developments and applications of dual-beam radiography for air
      cargo inspection. These developments include dual high-energy X-ray techniques as
      well as fast neutron and gamma-ray (or X-ray) radiography systems. High-energy X
      ray systems have the advantage of generally better penetration than neutron
      systems, depending on the material being interrogated. However, neutron systems
      have the advantage of much better sensitivity to material composition compared to
      dual high-energy X-ray techniques. In particular, fast neutron radiography offers
      the potential to discriminate between various classes of organic material, unlike
      dual energy X-ray techniques that realistically only offer the ability to
      discriminate between organic and metal objects.

PMID- 18054494
TI  - Does video-mediastinoscopy improve the results of conventional mediastinoscopy?
AB  - OBJECTIVE: Despite new technologies, mediastinoscopy remains the gold standard
      for mediastinal staging of lung cancer even though the procedure is not
      standardised. Introduction of video-mediastinoscopy (VM) may help to overcome
      this problem as it better visualises the anatomy and allows a more uniform
      dissection than conventional mediastinoscopy (CM). Does the use of VM result in
      more lymph node tissue, higher accuracy and lower complication rates as compared
      to CM? METHODS: All mediastinoscopies from June 2003 to December 2005 were
      analysed. In a protocol surgeons documented location of lymph node stations,
      number of lymph nodes resected or biopsied and technique (VM or CM). Two groups
      were created for analysis: group 1 (n=366) consisting of all mediastinoscopies
      was reviewed for complication rates; group 2 included all patients with lung
      cancer who had a pN0 status by mediastinoscopy and underwent subsequent
      thoracotomy (n=171). This group was studied for the number of lymph nodes
      resected or biopsied according to the technique (VM or CM), on accuracy and
      negative predictive value. RESULTS: Of 366 mediastinoscopies, 132 were CM (36.1%)
      and 234 VM (63.9%). Complications occurred in 17 patients (4.6%): 9 recurrent
      laryngeal nerve palsies (VM 2.1%, CM 3.0%), 5 mediastinal enlargement on routine
      chest radiography interpreted as postoperative bleeding (VM 0.9%, CM 2.3%),
      pneumonia (1), intraoperative laceration of the pleura (1) and main bronchus (1),
      both corrected during the procedure (all VM 1.3%). No intraoperative haemorrhage
      or death occurred. VM resected more lymph nodes (mean 8.1, range 3-25) then CM
      (mean 6.0, range 3-11), for all mediastinoscopies the mean lymph node yield was
      7.6 (range 3-25). Comparison of lymphadenectomy via thoracotomy in patients
      classified pN0 by mediastinoscopy (n=171) showed an accuracy of 87.9% for VM
      versus 83.8% for CM (85.8% for all mediastinoscopies) with a negative predictive
      value of 0.83 for VM and 0.81 for CM (0.82 for all mediastinoscopies).
      CONCLUSION: This study demonstrates that in comparison with CM, VM routinely
      yields more lymph nodes with fewer complications with a tendency towards better
      accuracy and negative predictive value. For these reasons, we believe that VM
      should replace CM as the method of choice. Furthermore VM would allow
      standardisation, thereby having an advantage in comparison to the less invasive
      newer staging techniques. This way mediastinoscopy could remain the gold standard
      despite its invasiveness.

PMID- 18054495
TI  - Autologous pericardial pulmonary conduit with single point attached commissures
      in a sheep model.
AB  - OBJECTIVE: For the surgical treatment of congenital heart disease and in Ross
      procedure a valved conduit is frequently required. Since homografts are not
      readily available in every country, a reliable alternative is needed. We
      developed a novel technique to construct a valved pulmonary conduit with single
      point attached commissures (SPAC) in a simple and fast way from a small strip of
      autologous pericardium, molded and briefly treated with glutaraldehyde. METHODS:
      Autologous pericardial pulmonary conduit was constructed intraoperatively and
      implanted in pulmonary position in a beating heart in six sheep. The prosthesis
      size was 31 mm for all sheep and the construction time (including 10 min
      glutaraldehyde treatment) was 19.0+/-3.3 min. Implantation time and
      cardiopulmonary by-pass was 27.3+/-5.4 min and 40.5+/-7.7 min, respectively. The
      sheep were euthanized after 6 months (222.7+/-5.8 days) postoperatively. RESULTS:
      In all sheep, the autologous pericardial valve was immediately competent. At
      sacrifice, the pericardial valve was pliable and competent in all cases with SPAC
      well anchored to the pericardial conduit wall. The maximum transvalvular gradient
      at implant and at sacrifice was 3.3+/-2.8 mmHg and 3.3+/-2.0 mmHg, respectively.
      CONCLUSIONS: This novel autologous pericardial pulmonary conduit with SPAC can be
      reliably produced in a very short time intraoperatively before cardiopulmonary by
      pass. The simplicity of construction, biocompatibility and freedom of stenosis or
      thrombosis makes this autologous pulmonary conduit especially useful for patients
      at locations where homografts are not readily available.

PMID- 18054496
TI  - Are trefoil factors oncogenic?
AB  - Trefoil factors (TFFs), in particular TFF1, are classical estrogen-regulated
      genes and have served as markers of estrogen gene regulation by various
      environmental estrogens. TFFs are also regulated by several other factors
      including growth hormone (hGH), insulin-like growth factor-1 (IGF-1), epidermal
      growth factor (EGF) and various oncogenic stimuli. TFFs are secreted proteins
      present in serum and possess the potential to act as growth factors promoting
      cell survival, anchorage-independent growth and motility. Recent compelling
      evidence has emerged from experimental and clinical studies to indicate a pivotal
      role of TFFs in oncogenic transformation, growth and metastatic extension of
      common human solid tumours. This review will summarize the current evidence for
      the involvement of TFFs in human cancer.

PMID- 18054497
TI  - Circulating and airway neutrophils in cystic fibrosis display different TLR
      expression and responsiveness to interleukin-10.
AB  - We compared blood neutrophils (PMNs) collected from healthy subjects with PMNs
      derived from either blood or airways collected from the same cystic fibrosis (CF)
      patients. When compared to healthy blood PMNs, CF blood PMNs expressed enhanced
      level of CD64, a marker of neutrophil activation, and lower level of Toll-like
      receptor-2 (TLR2). CF airway PMNs expressed enhanced level of TLR4. Interleukin-8
      (IL-8) production by CF blood PMNs could be enhanced upon addition of
      lipopolysaccharide or peptidoglycan, and this production was inhibited by
      recombinant human IL-10. In contrast, CF airway PMNs released spontaneously high
      level of IL-8 that was neither further enhanced by microbial activators nor
      inhibited by recombinant human IL-10. The levels of IL-10 receptors were similar
      in all types of neutrophils. These data further demonstrate that circulating PMNs
      from CF patients display a distinct pattern of surface markers, including TLRs,
      as compared to PMNs from healthy donors, and that airways PMNs from CF patients
      are primed and resistant to anti-inflammatory signals delivered by IL-10.

PMID- 18054498
TI  - Interaction of dendritic cells with biomaterials.
AB  - The interconnections between innate and adaptive immunity, with a focus on
      dendritic cells (DCs), in the context of combination products, are discussed.
      Biomaterials are shown to act as an adjuvant in the enhancement of the adaptive
      immune response to co-delivered antigen. Biomaterials are considered as agonists
      for DC maturation and several hypotheses as to the mechanism by which DCs
      recognize and respond to biomaterials are presented. There is the
      conceptualization of biomaterials with the idea of 'danger signals'. The goal is
      to design biomaterials to control DC phenotype and in this way control immune
      responses to combination products.

PMID- 18054499
TI  - Expression of active recombinant human lactoferrin in the milk of transgenic
      goats.
AB  - This report details the establishment of a transgenic goat model in order to
      produce human lactoferrin (hLf) in the mammary gland for large-scale application
      and research. Two transgenic male goats were generated by microinjecting sequence
      encoding hLf cDNA to the pronuclear. In the two lines, derived from the two
      founders, eight lactating female goats could secrete recombinant human
      lactoferrin (rhLf) at concentrations of up to 0.765 mg/ml. The method of
      purifying the rhLf from the milk was achieved using ion-exchange chromatography
      and resulted in 97% purity. Biochemical and physicochemical characteristics of
      rhLf were similar to native lactoferrin (nhLf); this included N-terminal
      sequence, isoelectric point, molecular mass, glycosylation, iron
      binding/releasing ability, thermal stability, and proteolysis. The rhLf showed
      broad spectrum antibacterial activity inhibiting the growth of several pathogenic
      bacterial strains. Also investigated, although to a lesser degree, was a
      practicable pasteurization method for the downstream processing of rhLf and,
      further, a method for the oral administration of rhLf. On the basis of these
      results, our studies show an optimistic and promising approach for the large
      scale production and therapeutic application of rhLf expressed in transgenic
      goats.

PMID- 18054500
TI  - Overexpression of post-translationally modified peptides in Escherichia coli by
      co-expression with modifying enzymes.
AB  - Post-translational modification plays crucial roles in signal transduction in
      eukaryotic cells. To elucidate the biological function of a protein with a
      specific post-translational modification, it is necessary to isolate the modified
      protein. However, it is difficult to incorporate a modified amino acid into a
      specific position of a protein, in particular, in a large-scale preparation. In
      order to prepare post-translationally modified proteins in Escherichia coli (E.
      coli), we have constructed co-expression vectors that contain protein and
      corresponding enzyme genes. The protein and enzyme are co-expressed in the same
      E. coli cells and the protein is post-translationally modified in vivo. By using
      this system, the transcriptional activator cyclic-AMP-response-element-binding
      protein (CREB) was phosphorylated at Ser-133 and the hypoxia-inducible factor
      1alpha (HIF-1alpha) was hydroxylated at Asn-803 in E. coli. Although the
      constructs of the proteins we used are very flexible and susceptible to
      degradation by proteases in E. coli when they are expressed alone, the B1 domain
      of streptococcal protein G (GB1) fused to the N-terminus of the proteins
      increased the yields dramatically. Site-specific phosphorylation of CREB and
      hydroxylation of HIF-1alpha were confirmed by matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) and NMR. Our GB1-fusion co
      expression system can be used in the same way as conventional protein expression
      in E. coli, making it a flexible and economical method to produce a large amount
      of a post-translationally modified protein.

PMID- 18054501
TI  - The cell centered database project: an update on building community resources for
      managing and sharing 3D imaging data.
AB  - Databases have become integral parts of data management, dissemination, and
      mining in biology. At the Second Annual Conference on Electron Tomography, held
      in Amsterdam in 2001, we proposed that electron tomography data should be shared
      in a manner analogous to structural data at the protein and sequence scales. At
      that time, we outlined our progress in creating a database to bring together cell
      level imaging data across scales, The Cell Centered Database (CCDB). The CCDB was
      formally launched in 2002 as an on-line repository of high-resolution 3D light
      and electron microscopic reconstructions of cells and subcellular structures. It
      contains 2D, 3D, and 4D structural and protein distribution information from
      confocal, multiphoton, and electron microscopy, including correlated light and
      electron microscopy. Many of the data sets are derived from electron tomography
      of cells and tissues. In the 5 years since its debut, we have moved the CCDB from
      a prototype to a stable resource and expanded the scope of the project to include
      data management and knowledge engineering. Here, we provide an update on the CCDB
      and how it is used by the scientific community. We also describe our work in
      developing additional knowledge tools, e.g., ontologies, for annotation and query
      of electron microscopic data.

PMID- 18054502
TI  - Bioorganic/inorganic hybrid composition of sponge spicules: matrix of the giant
      spicules and of the comitalia of the deep sea hexactinellid Monorhaphis.
AB  - The giant basal spicules of the siliceous sponges Monorhaphis chuni and
      Monorhaphis intermedia (Hexactinellida) represent the largest biosilica
      structures on earth (up to 3m long). Here we describe the construction (lamellar
      organization) of these spicules and of the comitalia and highlight their organic
      matrix in order to understand their mechanical properties. The spicules display
      three distinct regions built of biosilica: (i) the outer lamellar zone (radius:
      >300 microm), (ii) the bulky axial cylinder (radius: <75 microm), and (iii) the
      central axial canal (diameter: <2 microm) with its organic axial filament. The
      spicules are loosely covered with a collagen net which is regularly perforated by
      7-10 microm large holes; the net can be silicified. The silica layers forming the
      lamellar zone are approximately 5 microm thick; the central axial cylinder
      appears to be composed of almost solid silica which becomes porous after etching
      with hydrofluoric acid (HF). Dissolution of a complete spicule discloses its
      complex structure with distinct lamellae in the outer zone (lamellar coating) and
      a more resistant central part (axial barrel). Rapidly after the release of the
      organic coating from the lamellar zone the protein layers disintegrate to form
      irregular clumps/aggregates. In contrast, the proteinaceous axial barrel, hidden
      in the siliceous axial cylinder, is set up by rope-like filaments. Biochemical
      analysis revealed that the (dominant) molecule of the lamellar coating is a 27
      kDa protein which displays catalytic, proteolytic activity. High resolution
      electron microscopic analysis showed that this protein is arranged within the
      lamellae and stabilizes these surfaces by palisade-like pillars. The mechanical
      behavior of the spicules was analyzed by a 3-point bending assay, coupled with
      scanning electron microscopy. The load-extension curve of the spicule shows a
      biphasic breakage/cracking pattern. The outer lamellar zone cracks in several
      distinct steps showing high resistance in concert with comparably low elasticity,
      while the axial cylinder breaks with high elasticity and lower stiffness. The
      complex bioorganic/inorganic hybrid composition and structure of the Monorhaphis
      spicules might provide the blueprint for the synthesis of bio-inspired material,
      with unusual mechanical properties (strength, stiffness) without losing the
      exceptional properties of optical transmission.

PMID- 18054503
TI  - Quadriceps activity and physical activity profiles over long durations in
      patients with osteoarthritis of the knee and controls.
AB  - Exercise is recommended as a non-pharmacological, non-invasive intervention for
      osteoarthritis (OA) of the knee. Physiological data concerning the duration and
      intensity of muscle activity or physical activity profiles during normal daily
      activity for this population is lacking. Our aim was to explore this using
      surface Electromyography (EMG) and accelerometer-based activity monitoring.
      Thirty-four patients with knee OA, mean (SD) age 63.2 (9.8) years and 30 aged
      matched asymptomatic controls 64.1 (10.9) years participated. The duration of
      recording was similar in knee OA and control groups - median (IRQ range) 12:34
      (10:11-14:17)h and 13:10 (12:02-14:56)h, respectively (p=0.514). VM and VL were
      quiescent for 81.8 (75.3-91.0) to 89.2 (81.5-94.7)% of the time. VM was active
      for significantly longer durations than VL in the highest intensity band for
      those with knee OA (p=0.00), and for longer durations in those with knee OA
      compared to controls (p=0.027). The median (IRQ range) percentage of the total
      recording time spent in an upright posture was 32.4 (28.3-43.9)% and 38.8 (33.6
      45.8)%, and time spent stepping or walking was 12.7 (9.7-16.4)% and 16.0 (11.9
      19.6)% for those with knee OA and controls respectively. These novel data may
      prove useful for designing therapeutic exercise programmes and lifestyle changes
      for those with knee OA.

PMID- 18054505
TI  - The search for suitable prognostic markers for canine mammary tumors: A promising
      outlook.

PMID- 18054504
TI  - Protein synthesis inhibition and memory: formation vs amnesia.
AB  - Studies using protein synthesis inhibitors have provided key support for the
      prevalent view that memory formation requires the initiation of protein synthesis
      as a primary element of the molecular biology of memory. However, many other
      interpretations of the amnesia data have received far less attention. These
      include: (a) protein synthesis may play a constitutive role in memory formation,
      providing proteins prior to an experience that can be activated by training; (b)
      protein synthesis may be needed to replace proteins available prior to learning
      but 'consumed' by learning; (c) inhibition of protein synthesis impairs the well
      being of neurons, leading to an inability to deliver resources needed for memory
      formation; and (d) inhibition of protein synthesis results in abnormal neural
      functions that interfere with memory. One of these, abnormal release of
      neurotransmitters after inhibition of protein synthesis, is detailed here, along
      with a review of many circumstances in which it appears that protein synthesis at
      the time of training is not required for the formation of new memories. Evidence
      of activation of cell signaling molecules and transcription factors is another
      form of support for a role of training-initiated protein synthesis in memory.
      However, recent findings suggest that many of these molecules are activated by
      training and remain activated for days after training, i.e. activated for times
      well beyond those typically invoked for memory consolidation processes. Reviewing
      these results, this paper suggests that the long-lasting molecular changes may be
      the basis of a form of intracellular memory, one responsible for up-regulating
      the probability that a neuron, once activated in this manner, will engage in
      future plasticity. This view melds ideas of modulation of memory with those of
      consolidation of memory.

PMID- 18054506
TI  - Epstein-Barr virus acute encephalomyelitis in a 13-year-old boy.
AB  - The association of acute myelopathy and encephalopathy is reported in a 13-year
      old boy. Signs and symptoms of infectious mononucleosis, presence of heterophile
      antibodies, anticapsid antibodies and Epstein-Barr virus DNA detected in
      cerebrospinal fluid, disclosed a primary or reactivated infection by Epstein-Barr
      virus. Outcome was rapid and benign with complete clinical recovery in 1 month,
      after pulse therapy with methylprednisolone. Epstein-Barr virus is a known agent
      related to acute disseminated encephalomyelitis, by immune mediated mechanisms.
      However, in this case, cortical involvement in magnetic resonance imaging, short
      time between infectious mononucleosis and central nervous system manifestations,
      and the presence of viral DNA in cerebrospinal fluid, raised the possibility of a
      direct action of the virus in central nervous system. Acute myelopathy associated
      to Epstein-Barr virus encephalitis has been rarely reported in children.

PMID- 18054507
TI  - Delayed neurological signs following isolated parasagittal injury in asphyxia at
      term.
AB  - BACKGROUND: Parasagittal cerebral injury is a type of cerebral injury in term
      infants, which is characterized by the predominant injury of the arterial border
      zones of the anterior, middle and posterior cerebral arteries, however its early
      clinical manifestation is mostly unclear. AIM: To understand early clinical
      features of parasagittal cerebral injury. METHODS: The clinical details of 18
      newborn infants who were diagnosed as having parasagittal cerebral injury on
      magnetic resonance imaging (MRI). Eleven infants had localized injury within
      parasagittal regions ("Limited" group), 7 infants had diffuse extensive injury
      involving the deep gray matter and/or periventricular white matter ("Extensive"
      group). These infants were compared with 9 infants with perinatal asphyxia
      without MRI abnormalities ("Normal" group). RESULTS: There was no significant
      difference in the rate of cardiotocographic abnormalities, low Apgar scores, low
      blood pH and base excess, and the requirement for mechanical ventilation among
      three groups. Compared with the Normal group, fewer infants in the Limited group
      developed neonatal encephalopathy within an hour after birth. Neonatal seizures
      were more frequent in the Limited and the Extensive groups. Hepatic and/or renal
      dysfunction was more often observed in the Limited group. Cerebral palsy and/or
      mental retardation were common in the Extensive group. Electro-cortical
      depression was more in the Extensive group. Progressive suppression of electro
      cortical activity was common within infants in the Limited group (33%) and the
      Extensive group (60%). CONCLUSION: Infants with parasagittal cerebral injury
      developed serious neurological abnormalities despite less serious physiological
      and neurological manifestation shortly after birth, suggesting the importance of
      careful longitudinal observation of asphyxiated infants.

PMID- 18054508
TI  - Post-prandial alterations in LDL size and subclasses in patients with growth
      hormone deficiency.
AB  - OBJECTIVE: Several studies have suggested that lipoproteins generated during the
      post-prandial phase are highly atherogenic, with modifications in low-density
      lipoproteins (LDL) size and density. In the present study we assessed post
      prandial variations in LDL size and subclasses in patients with growth hormone
      deficiency (GHD). DESIGN: We studied in 12 hypopituitary patients with GHD and 10
      healthy control subjects matched for gender, age and body mass index (BMI) post
      prandial variations after a standardized meal consisting of 35% fat, 45%
      carbohydrate and 20% of protein (Clinutren Mix, Nestle) and containing calories
      corresponding to 1/3 of estimated basal metabolic rate. Blood samples were
      collected at baseline and after 2 and 4h to measure plasma lipids and LDL size
      and subclasses by nondenaturing polyacrylamide gradient gel electrophoresis.
      RESULTS: At baseline patients had similar plasma lipids than controls, with the
      exception of higher triglycerides (1.2+/-0.8 vs. 0.7+/-0.4mmol/L, p=.0024).
      Baseline LDL size was similar between the two groups and LDL subclass analysis
      revealed a small increase in LDL-IIIA (p=.0046). During post-prandial phase no
      significant differences were found in LDL size and subclasses in patients vs.
      controls with the sole exception of increased levels of LDL-IVB after 2h
      (p=.0295) and LDL-IIIB after 4h (p=.0478). CONCLUSIONS: It is, therefore,
      unlikely that a post-prandial variation in levels of small, dense LDL may
      significantly contribute to the atherogenic potential in hypopituitary patients
      with GHD.

PMID- 18054509
TI  - Quantitative physiological study of the fast dynamics in the intracellular pH of
      Saccharomyces cerevisiae in response to glucose and ethanol pulses.
AB  - Considering the effects of pH on many aspects of cell metabolism, such as its
      role in signaling processes and enzyme kinetics, it is indispensable to include
      the measurement of the dynamics of the intracellular pH, when studying the fast
      dynamic response of cells to perturbations. It has been shown previously that the
      intracellular pH rapidly drops following an increase in external glucose
      concentration [Kresnowati, M.T.A.P., Suarez-Mendez, C., Groothuizen, M.K., Van
      Winden, W.A., Heijnen, J.J., 2007. Measurement of fast dynamic intracellular pH
      in Saccharomyces cerevisiae using benzoic acid pulse. Biotechnol. Bioeng. 97, 86
      98; Ramos, S., Balbin, M., Raposo, M., Valle, E., Pardo, L.A., 1989. The
      mechanism of intracellular acidification induced by glucose in Saccharomyces
      cerevisiae. J. Gen. Microbiol. 135, 2413-2422; Van Urk, H., Schipper, D.,
      Breedveld, G.J., Mak, P.R., Scheffers, W.A., Van Dijken, J.P., 1989. Localization
      and kinetics of pyruvate-metabolizing enzymes in relation to aerobic alcoholic
      fermentation in Saccharomyces cerevisiae CBS 8066 and Candida utilis CBS 621.
      Biochim. Biophys. Acta 992(1), 78-86]. The mechanism for this fast intracellular
      acidification, however, has not been elucidated yet. This paper presents a
      metabolome-based analysis to reveal the physiological phenomena that cause the
      fast intracellular acidification following either a glucose pulse or an ethanol
      pulse to carbon-limited chemostat cultures of Saccharomyces cerevisiae. This
      quantitative study, which includes the determination of intracellular buffering
      capacity, the calculation of electric charge balance and the quantification of
      weak organic acid transport shows that none of the previously suggested
      mechanisms, i.e. increase in glucose phosphorylation and accumulation of CO(2),
      is sufficient to explain the measured decrease in intracellular pH following a
      glucose pulse.

PMID- 18054510
TI  - Short-chain acyl-CoA dehydrogenase gene mutation (c.319C>T) presents with
      clinical heterogeneity and is candidate founder mutation in individuals of
      Ashkenazi Jewish origin.
AB  - We report 10 children (7 male, 3 female), 3 homozygous for c.319C>T mutation and
      7 heterozygous for c.319C>T on one allele and c.625G>A variant on the other in
      the short-chain acyl-CoA dehydrogenase (SCAD) gene (ACADS). All were of Ashkenazi
      Jewish origin in which group we found a c.319C>T heterozygote frequency of 1:15
      suggesting the presence of a founder mutation or selective advantage. Phenotype
      was variable with onset from birth to early childhood. Features included
      hypotonia (8/10), developmental delay (8/10), myopathy (4/10) with multicore
      changes in two and lipid storage in one, facial weakness (3/10), lethargy (5/10),
      feeding difficulties (4/10) and congenital abnormalities (3/7). One female with
      multiminicore myopathy had progressive external ophthalmoplegia, ptosis and
      cardiomyopathy with pneumonia and respiratory failure. Two brothers presented
      with psychosis, pyramidal signs, and multifocal white matter abnormalities on MRI
      brain suggesting additional genetic factors. Two other infants also had white
      matter changes. Elevated butyrylcarnitine (4/8), ethylmalonic aciduria (9/9),
      methylsuccinic aciduria (6/7), decreased butyrate oxidation in lymphoblasts (2/4)
      and decreased SCAD activity in fibroblasts or muscle (3/3) were shown. Expression
      studies of c.319C>T in mouse liver mitochondria showed it to be inactivating.
      c.625G>A is a common variant in ACADS that may confer disease susceptibility.
      Five healthy parents were heterozygous for c.319C>T and c.625G>A, suggesting
      reduced penetrance or broad clinical spectrum. We conclude that the c.319C>T
      mutation can lead to wide clinical and biochemical phenotypic variability,
      suggesting a complex multifactorial/polygenic condition. This should be screened
      for in individuals with multicore myopathy, particularly among the Ashkenazim.

PMID- 18054511
TI  - The FDA announces new drug labeling for pharmacogenetic testing: is personalized
      medicine becoming a reality?

PMID- 18054512
TI  - Severe brain co-infection with Cryptococcus neoformans and Mycobacterium
      tuberculosis in a young, otherwise healthy student recently immigrated from
      China.
AB  - INTRODUCTION: While the incidence of pulmonary and extrapulmonary tuberculosis is
      growing in patients of advanced age, immunocompromised subjects, and immigrants
      coming in from developing countries [Keller A, Delavelle J, Howarth N, Bianchi S,
      Garcia J. Spinal and neurotuberculosis in an Asian immigrant. JBR-BTR 2002;85:136
      7; Sabbatani S, Manfredi R, Legnani G. Chiodo F. Tuberculosis in a metropolitan
      area of northern Italy: epidemiological trends and public health concerns. Eur J
      Epidemiol 2004;19:501-3], the concomitant occurrence of cerebral cryptococcosis
      plus brain and respiratory tuberculosis in a young and otherwise healthy patient,
      without an evident cause of immunodeficiency and without an obvious exposure, is
      exceedingly rare [Silber E, Sonnenberg P, Koornhof HJ, Morris L, Saffer D. Dual
      infective pathology in patients with cryptococcal meningitis. Neurology
      1998;51:1213-5.]. CASE REPORT: An exceptionally rare case of concurrent central
      nervous system infection with Cryptococcus neoformans and Mycobacterium
      tuberculosis in a 25-year-old otherwise healthy Chinese student, who had very
      recently joined an Italian post-doctoral course, is described. Also described are
      the diagnostic and therapeutic difficulties encountered in a five-month
      hospitalization period, when only transient and/or negligible immune system
      impairments were detected. CONCLUSIONS: This episode of very infrequent
      concurrent infections should emphasize the need to maintain an elevated clinical
      suspicion for opportunistic infections and tuberculosis, even in the absence of
      an obvious immunodeficiency and related epidemiological clues.

PMID- 18054513
TI  - WITHDRAWN: [Modelling the human body.]

PMID- 18054514
TI  - Adaptation of wavelet transform analysis to the investigation of biological
      variations in speech signals.
AB  - The purpose of this study was to adapt wavelet analysis as a tool for
      discriminating speech samples taken from healthy subjects across two biological
      states. Speech pressure waveforms were drawn from a study on effects of hormone
      fluctuations across the menstrual cycle on language functions. Speech samples
      from the vowel portion of the syllable 'pa', taken at the low- and high-hormone
      phases of the menstrual cycle, were extracted for analysis. Initial analysis
      applied Fourier transforms to examine the fundamental and formant frequencies.
      Wavelet analysis was used to investigate spectral differences at a more
      microbehavioural level. The key finding showed that wavelet coefficients for the
      fundamental frequency of speech samples taken from the high-hormone phase had
      larger amplitudes than those from the low-hormone phase. This study provided
      evidence for differences in speech across the menstrual cycle that affected the
      vowel portion of syllables. This evidence complements existing data on the
      temporal features of speech that characterise the consonant portion of syllables.
      Wavelet analysis provides a new tool for examination of behavioural differences
      in speech linked to hormonal variation.

PMID- 18054515
TI  - Cytokines, dendritic cells and immunological rejection.

PMID- 18054516
TI  - IFN regulation and functions in myeloid dendritic cells.
AB  - A central issue in dendritic cells (DC) biology is to understand how type I IFNs
      modulate the immuno-regulatory properties of DC. In this review I will address
      this issue in light of the recent experimental evidence on the expression and
      function of these cytokines in myeloid DC. This knowledge may have important
      therapeutic implications in infectious and neoplastic diseases and open new
      perspectives in the use of IFNs as vaccine adjuvants and in the development of DC
      based vaccines.

PMID- 18054517
TI  - Dendritic cells and cytokines in immune rejection of cancer.
AB  - Dendritic cells (DCs) play a crucial role in linking innate and adaptive immunity
      and, thus, in the generation of a protective immune response against both
      infectious diseases and tumors. The ability of DCs to prime and expand an immune
      response is regulated by signals acting through soluble mediators, mainly
      cytokines and chemokines. Understanding how cytokines influence DC functions and
      orchestrate the interactions of DCs with other immune cells is strictly
      instrumental to the progress in cancer immunotherapy. Herein, we will illustrate
      how certain cytokines and immune stimulating molecules can induce and sustain the
      antitumor immune response by acting on DCs. We will also discuss these cytokine
      DC interactions in the light of clinical results in cancer patients.

PMID- 18054518
TI  - Overcoming apoptosis deficiency of melanoma-hope for new therapeutic approaches.
AB  - The increased incidence of malignant melanoma in the last decades, its high
      mortality and pronounced therapy resistance pose an enormous challenge. Important
      therapeutic targets for melanoma are the induction of apoptosis and suppression
      of survival pathways. Preclinical studies have demonstrated the efficacy of pro
      apoptotic Bcl-2 proteins and of death receptor ligands to trigger apoptosis in
      melanoma cells. In the clinical setting, BH3 domain mimics and death receptor
      agonists are therefore considered as promising, specific novel treatments to add
      to the conventional pro-apoptotic strategies such as chemo- or radiotherapy.
      However, constitutively activated survival pathways, in particular the mitogen
      activated protein kinases, protein kinase B/Akt and nuclear factor (NF)-kappaB,
      all may work in concert to prevent effective therapy. Thus, selective biologicals
      developed with the aim to inhibit pro-survival signaling are currently tested in
      melanoma. For highly therapy-resistant tumors such as melanoma, development of
      novel drug combinations will be essential, and combinations of survival
      inhibitors and pro-apoptotic mediators appear most promising. The challenge of
      the near future will be to make a rational choice of the multiple possible
      combinations and protocols. This review gives a critical overview of proteins
      involved in melanoma chemoresistance, which are targets for current drug
      development leading to the best choice for future trials.

PMID- 18054519
TI  - Spectroscopic investigation of the donor-acceptor interaction between o
      phenylenediamine and tetracyanoethylene in dichloromethane.
AB  - The interaction between the electron donor o-phenylenediamine (o-phendn) and the
      pi-acceptor tetracyanoethylene (TCNE) has been investigated
      spectrophotometrically in dichloromethane at 25 degrees C. The results indicate
      that the reaction proceeds via two major steps. The formation of the 1:2 charge
      transfer complex [(o-phendn)2, (TCNE)4] in which two o-phenylenediamine molecules
      undergoes slow N-substitution by one TCNE forming the final reaction product 2,2
      di-o-aminoaniline-1,1-dicyanoethylene and 2HCN molecules. The reaction was
      studied using electronic, infrared, photometric titration and cyclic voltametric
      measurements. A general mechanism for the reactions is proposed.

PMID- 18054520
TI  - Effects of fatigue induced by neuromuscular electrical stimulation on postural
      control.
AB  - The aim was to investigate the effects of fatigue induced by electrical
      stimulation superimposed onto voluntary muscular contractions on postural
      abilities and strategy (n=8). Two groups of subjects performed a fatiguing of the
      triceps surae, the first by voluntary muscular contractions (group VOL) and the
      second (n=8) by electrical stimulation superimposed onto voluntary muscle
      contractions (group VOL+ES). Balance was measured before and after the completion
      of both fatiguing tasks, by using a force platform which recorded centre of foot
      pressure (COP). Spatio-temporal COP parameters were used to evaluate the postural
      abilities, and a frequency analysis of the COP excursions (Fast Fourier
      Transform) was performed to estimate the postural strategy (low frequencies
      mostly account for visuo-vestibular regulation and high frequencies for
      proprioceptive regulation). In the post-fatigue condition, spatio-temporal COP
      parameters were not modified in either group. However, the frequency analysis
      showed that the high frequency band increased more in group VOL than in group
      VOL+ES. Calf-muscles fatigue did not impair postural control but it generated a
      change of the contribution of the proprioceptive information (myotatic loops)
      greater in group VOL than in group VOL+ES. Calf-muscles fatigue induced a
      modification of the postural strategy that may be exerted more strongly after
      voluntary muscular contractions than after electrical stimulation superimposed
      onto voluntary muscular contractions.

PMID- 18054521
TI  - Western-medicine-validated anti-tumor agents and traditional Chinese medicine.

PMID- 18054522
TI  - Selection of genes of Mycobacterium tuberculosis upregulated during residence in
      lungs of infected mice.
AB  - In sequel to previous report [Srivastava V, Rouanet C, Srivastava R, Ramalingam
      B, Locht C, Srivastava BS. Macrophage-specific Mycobacterium tuberculosis genes:
      identification by green fluorescent protein and kanamycin resistance selection.
      Microbiology 2007;153:659-66], the genes of Mycobacterium tuberculosis
      upregulated during residence in lungs of infected mice were identified in an in
      vivo expression system based on kanamycin resistance. A promoter library of M.
      tuberculosis was constructed in a promoter trap shuttle vector pLL192 containing
      an artificial bicistronic operon composed of promoterless green fluorescent
      protein gene followed by kanamycin resistance gene. The library was introduced in
      M. bovis BCG and then infected in mice by intravenous route. Mice were treated
      twice daily with 40 mg/kg dose of kanamycin by intramuscular route for 21 days.
      Recombinant BCG recovered from the lungs were reinfected in mice to enrich clones
      surviving kanamycin treatment in the lung but sensitive to killing by kanamycin
      in vitro. After nucleotide sequencing of inserts from these clones, 20 genes
      belonging to fatty acids metabolism, membrane transport, nitric oxide defence and
      PE_PGRS/PPE family were identified. Real-time PCR analysis using RNA isolated
      from M. tuberculosis grown in vitro and from the lungs, confirmed upregulation of
      genes from 2 to 20-fold in vivo compared to growth in vitro. Several of these
      select 20 genes were also found upregulated ex vivo in macrophage-like cell line
      J774A.1, thus, suggesting a correlation in mycobacterial gene expression between
      ex vivo and in vivo conditions.

PMID- 18054523
TI  - Building a hospital referral expert system with a Prediction and Optimization
      Based Decision Support System algorithm.
AB  - This study presents a new method for constructing an expert system using a
      hospital referral problem as an example. Many factors, such as institutional
      characteristics, patient risks, traveling distance, and chances of survival and
      complications should be included in the hospital-selection decision. Ideally,
      each patient should be treated individually, with the decision process including
      not only their condition but also their beliefs about trade-offs among the
      desired hospital features. An expert system can help with this complex decision,
      especially when numerous factors are to be considered. We propose a new method,
      called the Prediction and Optimization-Based Decision Support System (PODSS)
      algorithm, which constructs an expert system without an explicit knowledge base.
      The algorithm obtains knowledge on its own by building machine learning
      classifiers from a collection of labeled cases. In response to a query, the
      algorithm gives a customized recommendation, using an optimization step to help
      the patient maximize the probability of achieving a desired outcome. In this
      case, the recommended hospital is the optimal solution that maximizes the
      probability of the desired outcome. With proper formulation, this expert system
      can combine multiple factors to give hospital-selection decision support at the
      individual level.

PMID- 18054524
TI  - Nucleotide sequence and phylogenetic analysis of a new potexvirus: Malva mosaic
      virus.
AB  - A filamentous virus isolated from Malva neglecta Wallr. (common mallow) and
      propagated in Chenopodium quinoa was grown, cloned and the complete nucleotide
      sequence was determined (GenBank accession # DQ660333). The genomic RNA is 6858
      nt in length and contains five major open reading frames (ORFs). The genomic
      organization is similar to members and the viral encoded proteins shared homology
      with the group of the Potexvirus genus in the Flexiviridae family. Phylogenetic
      analysis revealed a close relationship with narcissus mosaic virus (NMV),
      scallion virus X (ScaVX) and, to a lesser extent, to Alstroemeria virus X (AlsVX)
      and pepino mosaic virus (PepMV). A novel putative pseudoknot structure is
      predicted in the 3'-UTR of a subgroup of potexviruses, including this newly
      described virus. The consensus GAAAA sequence is detected at the 5'-end of the
      genomic RNA and experimental data strongly suggest that this motif could be a
      distinctive hallmark of this genus. The name Malva mosaic virus is proposed.

PMID- 18054526
TI  - Osteoarthritis in the context of ageing and evolution. Loss of chondrocyte
      differentiation block during ageing.
AB  - Ageing is the main risk factor of primary osteoarthritis (OA) and OA is the
      disease most strongly correlated with ageing. Both in humans and other animals OA
      development appears to be not strictly time-dependent but to hold pace with
      ageing processes. A characteristic of OA is deviant behaviour of chondrocytes in
      articular cartilage. These chondrocytes resemble terminal differentiated
      chondrocytes in growth plates and actively produce matrix degrading enzymes. The
      latter results in cartilage degeneration and eventually OA. We postulate that at
      a young age progression of chondrocyte differentiation is actively blocked in
      articular cartilage. This block declines when the evolutionary pressure to
      maintain this block, after reproductive life, is minimized. The loss of this
      differentiation block, maybe as a result of changes in chondrocyte TGF beta
      signalling, results in combination with normal joint loading in cartilage
      degeneration and OA.

PMID- 18054525
TI  - Mitochondrial regulation of flower development.
AB  - Flower development in plants depends not only on a set of nuclear genes but also
      on the coordinate action of the mitochondrion. Certain mitochondrial genomes in
      combination with certain nuclear genomes lead to the expression of cytoplasmic
      male-sterility (CMS). Both mitochondrial genes that determine male-sterility and
      nuclear Restorer-of-fertility genes that suppress the male-sterile phenotype have
      been cloned. Lately, the interactions between mitochondrial and nuclear genes
      through retrograde signalling in CMS-systems have been dissected. Of special
      interest are the altered expression patterns of floral homeotic genes in certain
      CMS-systems. Here, we review the mitochondrial influence on flower development
      and give examples from CMS-systems developed in Brassica, Daucus carota,
      Nicotiana tabacum and Triticum aestivum.

PMID- 18054527
TI  - Pronounced depression by propofol on carotid body response to CO2 and K+-induced
      carotid body activation.
AB  - Propofol is a commonly used anesthetic agent, and it attenuates hypoxic
      ventilatory response in humans. Propofol reduce in vivo and in vitro carotid body
      responses to hypoxia as well as to nicotine in experimental animals. In the
      present study we examined the effects of propofol on carotid body responses to
      hypercapnia and K(+)-induced carotid body activation and compared these effects
      with hypoxia in an in vitro rabbit carotid body preparation. Hypoxia, hypercapnia
      and potassium increased the carotid sinus nerve activity and propofol attenuated
      the chemoreceptor responses to all three stimuli. However, the magnitude of
      propofol-induced attenuation was greater for hypercapnic and K(+)-induced carotid
      body activation compared to the hypoxic response. These observations suggest that
      propofol-induced attenuation of the hypoxic response is partly secondary to
      depression of chemoreceptor response to hypercapnia inhibiting the synergistic
      interactions between O(2) and CO(2) and may involve CO(2)/H(+) sensitive K(+)
      channels.

PMID- 18054528
TI  - Increased levels of circulating progenitor cells after 1-week sojourn at moderate
      altitude (Austrian Moderate Altitude Study II, AMAS II).
AB  - We wanted to test if a sojourn at moderate altitude can activate circulation of
      adult progenitor cells in healthy individuals. Thus, we investigated 11 healthy
      volunteers, who spent 1-week at 1700 m (Oberlech, Austria,) simulating an active
      holiday. We measured circulating CD34(+) progenitor cell populations by flow
      cytometry and cytokines (using ELISA) in peripheral blood at baseline (500 m) and
      at the end of the sojourn. Extent of physical activity was documented via
      armband. CD34(+)CXCR-4(+) cells significantly increased in peripheral blood after
      the sojourn. CD34(+)CD31(+) and CD34(+)CD133(+) cells were upregulated in trend.
      Levels of SDF-1, G-CSF and VEGF decreased in trend whereas erythropoietin and SCF
      remained equal. Progenitor cells and degree of daily physical exercise did not
      correlate. We present the first study showing that exposure to moderate altitude
      with physical activity leads to increased levels of circulating progenitor cells.
      This effect may be due to hypoxia and/or physical activity.

PMID- 18054529
TI  - Development of a liquid chromatography-tandem mass spectrometry method for the
      determination of 23 endogenous steroids in small quantities of primate urine.
AB  - A quantitative method using liquid chromatography-tandem mass spectrometry (LC-MS
      MS) was developed for the simultaneous determination of 23 endogenous steroids in
      primate urine. The introduced method includes estrone, pregnandiol, cortisol,
      testosterone and several human urinary glucocorticoid and androgen metabolites.
      As the method is intended for the analysis of steroid hormones in behavioral
      studies on wild-living primates, it was adapted for a sample volume of 200microL
      urine. The sample preparation consisted of an enzymatic hydrolysis of steroid
      glucuronides using beta-glucuronidase from E. coli followed by a solvolytic
      cleavage of steroid sulfates employing sulfuric acid/ethyl acetate. The
      extraction of steroids from urine was optimized with respect to pH during
      extraction, type of ether and the amount of enzyme necessary for complete
      hydrolysis of glucuronides. The recovery of steroids spiked into urine before
      hydrolysis was 58.9-103.7% with an intra-day precision of 2.7-14.3% and an inter
      day precision of 2.9-14.8%. Detection limits ranged from 0.1-0.5ng/mL. The
      reproducibility of the whole sample preparation process was also demonstrated for
      unspiked urine (CV 1.2-16.5%). The proportion of steroid hormone excreted as
      sulfate was determined for 21 steroids in chimpanzee urine. The solvolysis proved
      to be essential for all investigated steroids except for pregnandiol,
      tetrahydrocortisol and tetrahydrocortisone, which were found to be less then 10%
      in the solvolysis fraction.

PMID- 18054530
TI  - Anisotropy of nickel release and corrosion in austenitic stainless steels.
AB  - The study of 316L-type stainless steel reveals a significant anisotropy of nickel
      release that is dependent on the orientation of the test surface with respect to
      the casting and rolling direction. Cross-sectional specimens (transversal cuts
      with respect to the rolling direction) show a substantially higher sensitivity to
      corrosion phenomena compared with longitudinal cuts and they release nickel ions
      at rates 10-100 times higher. These findings indicate that orientation needs to
      be taken into account when interpreting test results, in particular when
      comparing different grades of austenitic stainless steel, as well as in product
      and production design.

PMID- 18054531
TI  - Reconstruction of defects with the posterior femoral fasciocutaneous flap after
      resection of malignant tumours of the femoral greater trochanter, sacrococcygeal
      region and knee.
AB  - SUMMARY OBJECTIVE: To determine the vascular anatomy and clinical application of
      superiorly and inferiorly based posterior thigh fasciocutaneous flaps. METHODS:
      Ten consecutive patients were included in the study. All underwent resection of
      malignant tumours, five malignant fibrous histiocytomas (MFH), two synovial
      sarcomas, one skin squamous cell cancer, one malignant hamartoma and one
      fibrosarcoma. The average age of the patients was 49 years (range 25 to 71
      years), with six men and four women. Superior defects, including two in the
      sacrococcygeal region and one lesion over the femoral greater trochanter, were
      closed with superior posterior femoral fasciocutaneous flaps (SPFFCF). Seven
      lesions, three in the popliteal fossae, and two in the lateral and two medial
      knee regions, were closed with inferior posterior femoral fasciocutaneous flaps
      (IPFFCF). The average flap size was 148 cm(2) (ranging from 90 to 300 cm(2)). The
      average follow-up period was 23 months (ranging from 3 to 50 months). Patients
      were assessed by examination of the vascular anatomy, the operation technique and
      the treatment outcome. In particular the fasciocutaneous network and the
      descending branch of the inferior gluteal artery of the nutrient flap were
      analysed. RESULTS: There were no total skin flap failures and no significant
      complications. Tumours recurred locally in two patients and lung metastases
      occurred in another two. Five patients returned to their original jobs and daily
      activity without limitation, but two experienced decreased knee flexion of 30
      degrees . The larger SPFFCF is based on the fasciocutaneous branch of the
      inferior gluteal artery accompanied by the posterior gluteal cutaneous nerve.
      CONCLUSION: The larger SPFFCF, which includes the fascia lata femoris and the
      fasciocutaneous branch with the posterior femoral cutaneous nerve, does not
      include the first cutaneous branch of the fasciocutaneous branch artery. Hence,
      large defects of the sacrococcygeal region and the femoral greater trochanter can
      be reconstructed using an SPFFCF. Defects around the knee can be reconstructed
      with an IPFFCF, which is based on the ascending branch of the fasciocutaneous
      branch of the 3rd perforating artery.

PMID- 18054535
TI  - From animal models to model animals.

PMID- 18054536
TI  - Expanding the notion of disease in Huntington's disease.

PMID- 18054537
TI  - Electronic clinical challenges and images in GI. Menetrier's disease
      (hypoalbuminemic hyperplastic gastropathy).

PMID- 18054538
TI  - Electronic clinical challenges and images in GI. Acute stridor caused by hiatal
      hernia.

PMID- 18054539
TI  - Presidential address.

PMID- 18054542
TI  - Coronary artery disease associated with increased prevalence of colorectal
      tumors.

PMID- 18054543
TI  - American Gastroenterological Association to the Institute of Medicine: research
      needed to understand plight of the physician-investigator.

PMID- 18054544
TI  - Tracking down the stem cells of the intestine: strategies to identify adult stem
      cells.

PMID- 18054545
TI  - The challenges facing GI investigators today and what (more) the GI societies can
      do to help.

PMID- 18054546
TI  - Breath tests for gastrointestinal disease: the real deal or just a lot of hot
      air?

PMID- 18054547
TI  - Clinical challenges and images in GI. Small bowel obstruction caused by an
      intestinal phytobezoar.

PMID- 18054548
TI  - Clinical challenges and images in GI. Endometriosis of the sigmoid colon with
      endometriotic features within mesenteric lymph nodes.

PMID- 18054549
TI  - Identification of epithelial gaps in human small and large intestine by confocal
      endomicroscopy.
AB  - BACKGROUND & AIMS: Confocal endomicroscopy is an emerging technology that poses
      the endoscopist with challenges for identifying epithelial structures in the
      human intestine. We have shown previously that the murine intestinal epithelium
      is punctuated by gaps caused by cell shedding. The goals of this study were to
      determine if confocal endomicroscopy could resolve the presence of human
      epithelial gaps and whether a proinflammatory cytokine could increase cell
      shedding. METHODS: Intestinal mucosa was imaged after staining with acriflavine.
      Confocal endomicroscopy of 17 patients yielded 6277 images from the human
      terminal ileum and rectum. Results were validated by parallel studies of
      anesthetized mice (wild-type and Math1(DeltaIntestine)) using rigid confocal
      probe microscopy, 2-photon/confocal microscopy, and scanning electron microscopy.
      RESULTS: Human terminal ileal and rectal epithelium revealed unstained areas with
      the diameter of an individual epithelial cell, with 2 distinct morphologies. One
      had a "target" appearance, shown by mouse studies to be goblet cells. The other
      morphology had no nucleus and was observed by rigid confocal probe microscopy and
      scanning electron microscopy in the villi of Math1(DeltaIntestine) mice, which
      lack goblet cells. In the mouse, tumor necrosis factor alpha (0.33 microg/g
      intraperitoneally) increases cell shedding by 27-fold and caused loss of barrier
      function across 20% of resultant gaps. CONCLUSIONS: Confocal endomicroscopy can
      distinguish between epithelial discontinuities (gaps) and goblet cells in human
      intestine. Results suggest that the sealing of epithelial gaps must be considered
      as a component of the intestinal barrier and has potential implications for
      intestinal barrier dysfunction in human disease.

PMID- 18054550
TI  - Mortality by medication use among patients with inflammatory bowel disease, 1996
      2003.
AB  - BACKGROUND & AIMS: Most previous population-based studies of mortality in
      inflammatory bowel disease (IBD) did not account for medication use. We evaluated
      mortality by IBD medication use among members of the Kaiser Permanente Northern
      California IBD Registry. METHODS: The retrospective, population-based cohort
      study included 9032 persons who received at least one inpatient or 2 outpatient
      diagnoses of IBD during 1996-2002. Age and sex standardized mortality ratios
      measured the associations between IBD and all-cause and cause-specific mortality.
      Age, sex, and smoking adjusted odds ratios measured the association of mortality
      by IBD medication use. RESULTS: Compared with health plan members without IBD,
      mortality was increased in patients with Crohn's disease (CD) (1.4; 95%
      confidence interval, 1.2-1.6) but not ulcerative colitis (UC) (1.0; 95% CI, 0.9
      1.2). CD was associated with increased mortality from infectious and parasitic
      diseases (4.1; 95% CI, 1.7-8.5), septicemia (6.8; 95% CI, 2.2-15.8), small
      intestinal cancer (48.1; 95% CI, 5.8-17.4), respiratory diseases (1.9; 95% CI,
      1.3-2.7), digestive diseases other than IBD (2.4; 95% CI, 1.0-4.8), and liver
      diseases (2.6; 95% CI, 1.0-5.3). UC was associated with increased mortality from
      digestive diseases other than IBD (3.9; 95% CI, 2.4-6.0). The relationship with
      CD mortality was 0.7 for aminosalicylates (95% CI, 0.5-1.1), 1.3 (95% CI, 0.9
      1.9) for immunomodulators, and 1.0 (95% CI, 0.7-1.4) for corticosteroids. Among
      patients with UC, these odds ratios were 0.8 (95% CI, 0.5-1.1) for
      aminosalicylates, 0.5 (95% CI, 0.3-0.9) for immunomodulators, and 0.8 (95% CI,
      0.6-1.1) for corticosteroids. CONCLUSIONS: Mortality is increased in CD.
      Infections, respiratory diseases, and digestive diseases are important specific
      causes of death. IBD medication use has varying associations with mortality.

PMID- 18054551
TI  - Sleep deprivation is hyperalgesic in patients with gastroesophageal reflux
      disease.
AB  - BACKGROUND & AIMS: Studies have demonstrated that gastroesophageal reflux disease
      (GERD) can cause sleep deprivation because of nighttime heartburn or short,
      amnestic arousals during sleep. Sleep deprivation has been associated with
      reports of increased GERD severity. Our aim was to determine whether sleep
      deprivation enhances perception of intraesophageal acid in patients with GERD vs
      healthy controls. METHODS: Ten healthy controls and 10 patients with erosive
      esophagitis (grades B-D) were included in the study. All subjects were randomized
      to either sleep deprivation (1 night with </=3 hours of sleep) or sufficient
      sleep (3 days with >/=7 hours sleep/night). Patients crossed over to the other
      arm after a washout period of 1 week. To ensure proper sleep time, we objectively
      monitored subjects with an actigraph. The morning after sufficient sleep or sleep
      deprivation, patients underwent stimulus response functions to esophageal acid
      perfusion. RESULTS: Ten healthy controls and 10 GERD patients completed all
      stages of the study. GERD patients demonstrated a significant decrease in lag
      time to symptom report (91 +/- 21.6 vs 282.7 +/- 67 sec, respectively, P = .02),
      increase in intensity rating (9.3 +/- 1.4 vs 4.4 +/- 0.9 cm, respectively, P =
      .02), and increase in acid perfusion sensitivity score (48.3 +/- 8.5 vs 22.7 +/-
      4.5 sec x cm/100, respectively, P = .02) after sleep deprivation as compared with
      nights of good sleep. Normal subjects did not demonstrate any differences in
      stimulus response functions to acid between sufficient sleep and sleep
      deprivation (578 +/- 164 vs 493.8 +/- 60.3 sec, 0.3 +/- 0.2 vs 0.45 +/- 0.2 cm,
      and 0.4 +/- 0.3 vs 2.4 +/- 1.4 sec x cm/100, respectively, all P = NS).
      CONCLUSIONS: Sleep deprivation is hyperalgesic in patients with GERD and provides
      a potential mechanism for increase in GERD symptom severity in sleep-deprived
      patients.

PMID- 18054552
TI  - Glucose-dependent insulinotropic polypeptide enhances adipocyte development and
      glucose uptake in part through Akt activation.
AB  - BACKGROUND & AIMS: In addition to its role as the primary mediator of the
      enteroinsular axis, glucose-dependent insulinotropic polypeptide (GIP) may play a
      critical role in the development of obesity. The purpose of these studies was to
      characterize the effects of GIP and its receptor (GIPR) in adipocyte development
      and signaling. METHODS: Effects of GIP and GIPR on differentiated 3T3-L1 cells
      were analyzed using Western blot analysis, Oil-Red-O staining, cyclic adenosine
      monophosphate radioimmunoassay, immunofluorescence microscopy, and glucose uptake
      measurements. RESULTS: To determine whether GIP and GIPR are important components
      in adipocyte development, the expression profile of GIPR during differentiation
      was examined. GIPR protein expression was enhanced during the differentiation
      process, and coincubation with its ligand GIP augmented the expression of aP2, a
      fat cell marker. Conversely, the suppression of GIPR expression by a specific
      short hairpin RNA attenuated Oil-Red-O staining and aP2 expression, suggesting
      that the GIPR may play a critical role in adipocyte development. To investigate
      specific signaling components that may mediate the effects of GIP, we analyzed
      Akt, glucose transporter-4, and glucose uptake, all of which are modulated by
      insulin in fat cells. Like insulin, GIP induced the activation of Akt in a
      concentration-dependent manner, promoted membrane glucose transporter-4
      accumulation, and enhanced [(3)H]-2-deoxyglucose uptake. CONCLUSIONS: These
      studies provide further evidence for an important physiologic role for GIP in
      lipid homeostasis and possibly in the pathogenesis of obesity. Furthermore, our
      data indicate that the GIPR might represent a suitable target for the treatment
      of obesity.

PMID- 18054553
TI  - Improvement in survival associated with adult-to-adult living donor liver
      transplantation.
AB  - BACKGROUND & AIMS: More than 2000 adult-to-adult living donor liver
      transplantations (LDLT) have been performed in the United States, yet the
      potential benefit to liver transplant candidates of undergoing LDLT compared with
      waiting for deceased donor liver transplantation (DDLT) is unknown. The aim of
      this study was to determine whether there is a survival benefit of adult LDLT.
      METHODS: Adults with chronic liver disease who had a potential living donor
      evaluated from January 1998 to February 2003 at 9 university-based hospitals were
      analyzed. Starting at the time of a potential donor's evaluation, we compared
      mortality after LDLT to mortality among those who remained on the waiting list or
      received DDLT. Median follow-up was 4.4 years. Comparisons were made by hazard
      ratios (HR) adjusted for LDLT candidate characteristics at the time of donor
      evaluation. RESULTS: Among 807 potential living donor recipients, 389 underwent
      LDLT, 249 underwent DDLT, 99 died without transplantation, and 70 were awaiting
      transplantation at last follow-up. Receipt of LDLT was associated with an
      adjusted mortality HR of 0.56 (95% confidence interval [CI]: 0.42-0.74; P < .001)
      relative to candidates who did not undergo LDLT. As centers gained greater
      experience (>20 LDLT), LDLT benefit was magnified, with a mortality HR of 0.35
      (95% CI: 0.23-0.53; P < .001). CONCLUSIONS: Adult LDLT was associated with lower
      mortality than the alternative of waiting for DDLT. This reduction in mortality
      was magnified as centers gained experience with LDLT. This reduction in
      transplant candidate mortality must be balanced against the risks undertaken by
      the living donors themselves.

PMID- 18054554
TI  - Prevalence of elevated alanine aminotransferase among US adolescents and
      associated factors: NHANES 1999-2004.
AB  - BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a common cause of
      liver disease in children and adolescents. The majority of studies of NAFLD in
      children have been in select populations of the clinically obese. Study aims were
      to estimate the prevalence of elevated alanine aminotransferase (ALT, as a marker
      of NAFLD) in a general contemporary adolescent population and to identify leading
      risk factors for ALT elevation (>30 U/L). METHODS: We analyzed data of adolescent
      participants (aged 12-19 years; N = 5586) in the National Health and Nutrition
      Examination Survey 1999-2004, a representative sample of the civilian
      noninstitutionalized US population. RESULTS: The prevalence of elevated ALT
      levels (>30 U/L) was 7.4% among white adolescents, 11.5% among Mexican American
      adolescents, and 6.0% among black adolescents. Elevated ALT levels were prevalent
      in 12.4% of male subjects compared with 3.5% of female subjects. Multivariable
      associations with elevated ALT levels were found for sex (odds ratio [OR] male vs
      female, 7.7; 95% confidence interval [CI], 3.9-15.1), ethnicity (OR black vs
      white, 0.6; 95% CI, 0.3-1.3; OR Mexican American vs white, 1.6; 95% CI, 1.0-2.6),
      waist circumference (OR per 1 SD, 1.4; 95% CI, 1.0-2.0), and fasting insulin
      level (OR per 1 SD, 1.6; 95% CI, 1.2-2.1). Age, C-reactive protein levels, and
      triglyceride levels were also positively and socioeconomic position inversely
      associated with elevated ALT levels. The magnitude of associations were similar
      across ethnic groups. CONCLUSIONS: ALT level is associated with waist
      circumference and insulin resistance even in a young population. These
      characteristics could be utilized to identify adolescents who may benefit from
      screening for NAFLD, offering an opportunity to prevent disease progression at an
      early age.

PMID- 18054555
TI  - Reduction in hepatitis C-related liver disease associated with GB virus C in
      human immunodeficiency virus coinfection.
AB  - BACKGROUND & AIMS: It has been reported that GB virus C infection (GBV-C) leads
      to improved morbidity and mortality in patients with human immunodeficiency virus
      (HIV) infection. However, GBV-C has no effect on the course of liver disease in
      hepatitis C virus (HCV) monoinfection. The aim of the study was to determine the
      influence of GBV-C infection on liver disease in patients with HCV/HIV
      coinfection. METHODS: Data on 158 HCV/HIV patients were collected from January
      1996 to October 2005. Two plasma specimens, collected at least 18 months apart,
      were tested for GBV-C RNA by reverse transcription-polymerase chain reaction with
      primers to the NS5B gene and confirmed using E2 gene primers and sequencing.
      Antibodies to GBV-C E2 protein were also determined. Liver-related morbidity and
      mortality were assessed from patient records. RESULTS: Fifty-seven of 158 (36%)
      patients had GBV-C RNA and 94 (59%) had evidence of exposure to GBV-C based on
      combined polymerase chain reaction and antibody results. Thirty-four (21%)
      patients had features of cirrhosis, with 20 having compensated and 14 having
      decompensated cirrhosis. Active GBV-C RNA was significantly associated with a
      reduction in cirrhosis, both compensated and decompensated in multivariate
      analysis (hazard ratio, 0.27; 95% confidence interval, 0.08-0.88; P = .03), as
      well as in analysis for cirrhosis-free survival vs duration of HCV infection (P =
      .006). No significant effect on liver-related or overall survival was observed.
      CONCLUSIONS: In these HCV/HIV-coinfected patients, GBV-C RNA was associated with
      a significant reduction in the severity of HCV-related liver disease.

PMID- 18054556
TI  - Predictive molecular markers for colorectal cancer patients with resected liver
      metastasis and adjuvant chemotherapy.
AB  - BACKGROUND & AIMS: The aims of the study were to evaluate the predictive value of
      8 candidate molecular markers for colorectal cancer (CRC) patients receiving
      hepatic arterial infusion (floxuridine [FUDR] and dexamethasone) and systemic
      irinotecan (CPT11) post resection of liver metastasis. METHODS: RNA was extracted
      from microdissected tumor cells of fixed and embedded specimens of resected liver
      metastases (94 cases) and analyzed by quantitative reverse-transcription
      polymerase chain reaction (RT-PCR) for thymidine phosphorylase, dihydropyrimidine
      dehydrogenase, thymidylate synthase, uridine phosphorylase, uridine/cytidine
      (monophospho)kinase, Bcl-2 related protein, Cyclin-D1, and Survivin expression.
      Uni- and multivariate statistical analyses and an explorative hierarchical
      clustering analysis of quantitative RT-PCR data were performed for overall
      survival and recurrent disease. RESULTS: After adjustment for multiple
      clinicopathologic parameters, none of the markers were significantly associated
      with overall survival (except, marginally, Cyclin-D1; P = .06) or extrahepatic
      recurrence. However, high Survivin (P = .03) and Cyclin-D1 (P = .05) levels were
      predictive for hepatic recurrence. Hierarchical cluster analysis identified 7 of
      94 patients associated with lower hepatic recurrence (P < .001). This patient
      group was characterized by low Cyclin-D1 and Survivin messenger RNA levels, both
      genes also clustering together. CONCLUSIONS: Cyclin-D1 and Survivin messenger RNA
      analyzed by standardized, quantitative RT-PCR are predictive markers for CRC
      patients receiving hepatic arterial infusion (FUDR/dexamethasone) and systemic
      CPT11 post resection of liver metastasis. Moreover, our exploratory hierarchical
      cluster analysis of quantitative RT-PCR data supports its potential as an
      application to define clinically relevant patient subgroups.

PMID- 18054557
TI  - Epigenetic and genetic alterations in Netrin-1 receptors UNC5C and DCC in human
      colon cancer.
AB  - BACKGROUND & AIMS: DCC and UNC5C, Netrin-1 dependence receptors, perform an
      important role in intestinal epithelial biology. Both receptors frequently are
      down-regulated in colorectal cancer (CRC). Although CRCs frequently lose DCC
      owing to deletions at 18q, the mechanism for the UNC5C loss is poorly understood.
      We hypothesized that UNC5C is silenced epigenetically in CRC, and that there are
      interactions between losses of UNC5C and DCC in colorectal tumorigenesis.
      METHODS: Gene expression and epigenetic analysis of UNC5C was examined in 8 CRC
      cell lines, 147 sporadic CRCs with corresponding normal mucosa, and 52
      adenomatous polyps (APs). Allelic imbalances at DCC were determined in CRCs. The
      molecular analyses were compared with genetic and clinicopathologic features.
      RESULTS: All CRC cell lines showed UNC5C methylation and an associated loss of
      gene expression. Treatment with 5-Aza-2'-deoxycytidine resulted in restoration of
      gene transcription. UNC5C methylation was significantly higher in CRCs (76.2%)
      and APs (63.5%) than in corresponding normal mucosa (6%; P < .0001). Allelic
      imbalance at DCC was observed in 61% of CRCs. Overall, 89.3% of CRCs had
      alterations of one of the dependence receptors. UNC5C methylation occurred
      predominantly in the earlier lesions (APs and early CRCs), whereas DCC losses
      were more often in advanced CRCs. CONCLUSIONS: The majority of CRCs harbor
      defects in Netrin-1 receptors, emphasizing the importance of this growth
      regulatory pathway in cancer. Furthermore, the timing of the molecular
      alterations in the Netrin-1 receptors is not random because UNC5C inactivation
      occurs early, whereas DCC losses occurs in later stages of multistep colorectal
      carcinogenesis.

PMID- 18054558
TI  - 5-Fluorouracil is efficiently removed from DNA by the base excision and mismatch
      repair systems.
AB  - BACKGROUND & AIMS: 5-Fluorouracil (FU) is one of the mainstays of colon cancer
      chemotherapy. Although developed as an inhibitor of thymidylate synthase, its
      cytotoxicity has been linked also to its incorporation into RNA. Surprisingly,
      although FU is incorporated also into DNA, little is known about its metabolism
      in this nucleic acid. METHODS: Using extracts of human cells and circular DNA
      substrates containing a single FU residue either paired with adenine or mispaired
      with guanine, we studied the enzymology of FU processing. RESULTS: In nicked
      circular substrates, FU/G mispairs were efficiently repaired by mismatch repair
      (MMR). In covalently closed circular DNA, which is refractory to MMR, FU/G repair
      was initiated by either thymine-DNA glycosylase or uracil-DNA glycosylase,
      whereas FU/A pairs were processed by UNG. Methylated CpG binding domain 4 protein
      and single-strand selective monofunctional uracil-DNA glycosylase 1 did not
      detectably contribute to FU removal; however, because these recombinant enzymes
      process FU/G and FU/A in oligonucleotide substrates, respectively, they too may
      be involved in FU metabolism in vivo. CONCLUSIONS: The functional redundancy of
      MMR and DNA glycosylases in FU processing should ensure that the drug is
      efficiently removed from DNA before it can interfere with essential DNA metabolic
      processes, such as transcription. However, in FU-treated cells, the nucleotide
      pools are depleted of thymine. The repair synthesis might thus be inhibited and
      leave cytotoxic gaps or breaks in DNA. Moreover, FU and/or 5-fluorouracil-2'
      deoxyuridine-5'-triphosphate removed from DNA will increase the intracellular
      concentration of the drug and thus exacerbate its cytotoxicity.

PMID- 18054560
TI  - Aggravation of different types of experimental colitis by depletion or adhesion
      blockade of neutrophils.
AB  - BACKGROUND & AIMS: Neutrophils are generally thought to play an important
      proinflammatory role in the pathogenesis of inflammatory bowel disease. The
      objective of this study was to evaluate whether blocking the invasion of
      neutrophils by anti-L-selectin monoclonal antibodies modulates chemically induced
      colitis and how this modulation is accomplished. METHODS: Trinitrobenzene
      sulfonic acid/dinitrobenzene sulfonic acid (TNBS/DNBS)-induced colitis was
      studied in rats on treatment with anti-L-selectin monoclonal antibodies (mAb) or
      antineutrophil antiserum. Different anti-L-selectin mAb, either blocking or
      nonblocking, as well as F(ab)(2) fragments were evaluated. Additionally,
      leukocyte migration was examined using intravital microscopy. Furthermore, the
      effect of neutrophil depletion in rat TNBS-induced colitis was studied either
      prior to or after colitis induction as well as murine CD4(+)CD45RB(high) transfer
      colitis. Finally, bacterial translocation during DNBS-induced colitis was studied
      in neutrophil-depleted and control rats. RESULTS: Anti-L-selectin mAb treatment
      resulted in increased mortality and bowel inflammation as well as hemorrhagic eye
      secretion. No clear difference was found between blocking and nonblocking mAb or
      F(ab)(2) fragments. For all investigated antibodies/fragments, either complete
      blockade of leukocyte invasion or marked neutrophil depletion was found.
      Accordingly, neutrophil depletion by antiserum resulted in aggravation of rat
      DNBS-induced colitis as well as murine transfer colitis. CONCLUSIONS: Adhesion
      blockade or neutrophil depletion aggravates rat TNBS/DNBS-induced colitis
      together with extraintestinal manifestations of the eyes. Therefore, neutrophils
      appear to have an important role in mucosal repair processes. Importantly,
      adhesion blockade as a therapeutic concept can be detrimental in inflammatory
      bowel disease.

PMID- 18054559
TI  - Toll-like receptor-4 promotes the development of colitis-associated colorectal
      tumors.
AB  - BACKGROUND & AIMS: Chronic inflammation is a risk factor for colon cancer in
      patients with ulcerative colitis (UC). The molecular mechanisms linking
      inflammation and colon carcinogenesis are incompletely understood. We tested the
      hypothesis that Toll-like receptor 4 (TLR4) is involved in tumorigenesis in the
      setting of chronic inflammation. METHODS: Tissues from UC patients with cancer
      were examined for TLR4 expression. Colitis-associated neoplasia was induced using
      azoxymethane injection followed by dextran sodium sulfate treatment in TLR4
      deficient or wild-type mice. Inflammation, polyps, and microscopic dysplasia were
      scored. Cyclooxygenase (Cox)-2 and prostaglandin E(2) production were analyzed by
      real-time polymerase chain reaction, immunohistochemistry, or enzyme immunoassay.
      Epidermal growth factor receptor (EGFR) phosphorylation and amphiregulin
      production were examined by Western blot analysis and enzyme-linked immunosorbent
      assay, respectively. RESULTS: We show that TLR4 is overexpressed in human and
      murine inflammation-associated colorectal neoplasia. TLR4-deficient mice were
      protected markedly from colon carcinogenesis. Mechanistically, we show that TLR4
      is responsible for induction of Cox-2, increased prostaglandin E(2) production,
      and activation of EGFR signaling in chronic colitis. Amphiregulin, an EGFR
      ligand, was induced in a TLR4, Cox-2-dependent fashion and contributes to
      activation of EGFR phosphorylation in colonic epithelial cells. CONCLUSIONS: TLR4
      signaling is critical for colon carcinogenesis in chronic colitis. TLR4
      activation appears to promote the development of colitis-associated cancer by
      mechanisms including enhanced Cox-2 expression and increased EGFR signaling.
      Inhibiting TLR4 signaling may be useful in the prevention or treatment of colitis
      associated cancer.

PMID- 18054562
TI  - Allergen-IgE complexes trigger CD23-dependent CCL20 release from human intestinal
      epithelial cells.
AB  - BACKGROUND & AIMS: In food allergic individuals, exposure to food allergens by
      the oral route can trigger immediate (within minutes) local hypersensitivity
      reactions in the intestine followed by a late-phase inflammatory response.
      Previous work has shown that CD23 is constitutively expressed by human intestinal
      epithelial cells and mediates the uptake of allergen-IgE complexes. We
      hypothesized that allergen-IgE complexes could also signal via CD23 to trigger an
      inflammatory cascade in the local environment. METHODS: Caco-2 monolayers were
      stimulated with human IgE-antigen (Ag) complexes. IL-8 and CCL20 mRNA and protein
      were determined by RT-PCR and ELISA, respectively. Signaling pathways were
      assessed by immunoblotting. Endogenous CD23 expression was knocked down by stable
      transfection with CD23 shRNA retroviral plasmid. Migration assays were performed
      using human monocyte-derived dendritic cells. RESULTS: Stimulation of Caco-2
      cells with IgE-Ag complexes triggered upregulation of IL-8 and CCL20 at the mRNA
      and protein level. Allergen complexes induced phosphorylation of ERK and JNK, but
      not p38 MAP kinase or NK-kappaB, and resulted in AP-1 activation. Cross-linking
      of CD23 replicated the findings with IgE-Ag complexes, and silencing of CD23
      expression abrogated the response to allergen-IgE complexes. Supernatant from IgE
      Ag-stimulated epithelial cells induced migration of dendritic cells in a CCL20
      dependent manner. Finally, immunostaining of duodenal biopsies demonstrated that
      CCL20 was constitutively expressed by epithelial cells in vivo. CONCLUSIONS:
      Signaling via epithelial CD23 may participate in the late-phase inflammatory
      response by the release of chemokines capable of recruiting antigen presenting
      cells and effector cells of allergic inflammation.

PMID- 18054561
TI  - Translational inhibition of colonic epithelial heat shock proteins by IFN-gamma
      and TNF-alpha in intestinal inflammation.
AB  - BACKGROUND & AIMS: Inducible heat shock proteins (iHsp), Hsp25/27 and Hsp70, play
      essential roles in protecting cells against stress and, in intestinal mucosal
      inflammation, potentially lessening the extent and severity of injury. We
      examined the expression and regulation of iHsp in human and experimental
      inflammatory bowel diseases (IBD) and in vitro. METHODS: iHsp expression and
      regulation were assessed in normal and IBD colonic biopsy specimens, IL-10(-/-)
      mice, and young adult mouse colonic epithelial cells by immunohistochemistry,
      Western blot, and real-time polymerase chain reaction (PCR). Phosphorylation of
      double-stranded RNA-dependent protein kinase (PKR) and eukaryotic initiation
      factor-2alpha (eIF-2alpha) was determined by Western blot. RESULTS: Hsp25/27 and
      Hsp70 levels were selectively reduced in areas of active mucosal inflammation
      associated with human IBD and IL-10(-/-) mice with colitis. Wild-type mice
      treated in vivo with interferon (IFN)-gamma + tumor necrosis factor (TNF)-alpha
      also demonstrated reduced colonic Hsp25/27 and Hsp70. In young adult mouse
      colonic epithelial cells, IFN-gamma+TNF-alpha inhibited heat induction of
      Hsp25/27 and Hsp70, an effect not associated with changes in iHsp messenger RNA
      or protein half-lives but caused by suppressed de novo iHsp synthesis. IFN
      gamma+TNF-alpha cotreatment activated PKR, resulting in phosphorylation and
      inactivation of eIF-2alpha, an essential factor in protein translation. These
      effects were not due to induced apoptosis and could be negated by PKR-inhibitor
      and short interfering RNA to PKR. Increased phosphorylation of PKR and eIF-2alpha
      were also observed in active IBD tissues. CONCLUSIONS: Mucosal inflammation is
      associated with iHsp down-regulation, an effect that appears mediated by
      translational down-regulation by proinflammatory cytokines. In the context of
      IBD, we propose that this mechanism contributes to the severity, extent, and
      persistence of inflammation-induced mucosal injury.

PMID- 18054563
TI  - Down-regulation of the monocarboxylate transporter 1 is involved in butyrate
      deficiency during intestinal inflammation.
AB  - BACKGROUND & AIMS: Butyrate oxidation is impaired in intestinal mucosa of
      patients with inflammatory bowel diseases (IBD). Butyrate uptake by colonocytes
      involves the monocarboxylate transporter (MCT) 1. We aimed to investigate the
      role of MCT1 in butyrate oxidation deficiency during colonic inflammation.
      METHODS: Colonic tissues were collected from patients with IBD or healthy
      controls and from rats with dextran sulfate sodium (DSS)-induced colitis. The
      intestinal epithelial cell line HT-29 was treated with interferon-gamma (IFN
      gamma) and tumor necrosis factor-alpha (TNF-alpha). MCT1 expression was analyzed
      by real-time reverse-transcription polymerase chain reaction, Western blot, and
      immunofluorescence. Butyrate uptake and oxidation in HT-29 cells was assessed
      using [(14)C]-butyrate. The mechanism of MCT1 gene regulation was analyzed by
      nuclear run-on and reporter gene assays. RESULTS: MCT1 messenger RNA (mRNA) and
      protein levels were markedly decreased in inflamed colonic mucosa of IBD patients
      and rats. In HT-29 cells, down-regulation of MCT1 mRNA and protein abundance by
      IFN-gamma and TNF-alpha correlated with a decrease in butyrate uptake and
      subsequent oxidation. IFN-gamma and TNF-alpha did not affect MCT1 mRNA stability
      but rather down-regulated gene transcription. We demonstrate that the cytokine
      response element is located in the proximal -111/+213 core region of the MCT1
      promoter. CONCLUSIONS: The data suggest that butyrate oxidation deficiency in
      intestinal inflammation is a consequence of reduction in MCT1-mediated butyrate
      uptake. This reinforces the proposition that butyrate oxidation deficiency in IBD
      is not a primary defect.

PMID- 18054564
TI  - Amelioration of cystic fibrosis intestinal mucous disease in mice by restoration
      of mCLCA3.
AB  - BACKGROUND & AIMS: Mice deficient of the cystic fibrosis (CF) transmembrane
      conductance regulator (CFTR) exhibit severe intestinal lesions, particularly
      mucous overproduction/secretion and accumulation, which is similar to meconium
      ileus in CF patients. Moreover, severity of the intestinal disease in CF mice is
      strongly influenced by genetic modifiers, and CFTR deficiency affects the
      expression of multiple secondary genes that may impact on the phenotype. The
      murine orthologue of human hCLCA1 (mCLCA3) is expressed by goblet cells and
      implicated in their normal function, particularly with mucus production/secretion
      that is exaggerated in CF; however, its influence on the CF intestinal disease,
      although suggested, remains unclear. METHODS: To investigate the role of mCLCA3
      on the CF intestinal disease in mice, its expression in this tissue has been
      assessed, and a CF mouse line maintaining elevated mCLCA3 levels has been
      developed and comprehensively characterized. RESULTS: Expression of mCLCA3 is
      significantly reduced in CF mouse intestines, although the number of goblet cells
      is elevated, indicating marked reduction per cell. Importantly, correction of
      this deficiency results in amelioration of the mucous-based disease leading to a
      marked improvement of intestinal pathology and survival, although goblet cell
      hyperplasia and hypertrophy were augmented. This intestinal amelioration did not
      appear to be related to rectification of the CF electrophysiologic defect.
      CONCLUSIONS: mCLCA3 has a role in intestinal goblet cell function that includes
      modification of the mucous properties and/or secretion that are altered in CF.
      Thus, elevation of mCLCA3 (hCLCA1) levels could provide a means to reduce
      intestinal mucous-based lesions in CF and related diseases.

PMID- 18054565
TI  - Aging gastropathy-novel mechanisms: hypoxia, up-regulation of multifunctional
      phosphatase PTEN, and proapoptotic factors.
AB  - BACKGROUND & AIMS: Aging gastric mucosa has impaired mucosal defense and
      increased susceptibility to injury. Our aims were to determine the mechanisms
      responsible for above abnormalities. METHODS: We used Fisher F-344 rats, 3 and 24
      months of age. We measured gastric mucosal blood flow; visualized mucosal
      hypoxia; examined expression of early growth response-1 transcription factor and
      phosphatase and tensin homologue deleted on chromosome 10 (PTEN); assessed
      apoptosis; and determined expression of caspase-3, caspase-9, and survivin. We
      also examined susceptibility of gastric mucosa of young and aging rats to ethanol
      injury and whether down-regulation of PTEN affects susceptibility of aging
      gastric mucosa to injury. To determine human relevance, we examined expression of
      PTEN and survivin in human gastric specimens of young and aging individuals.
      RESULTS: Gastric mucosa of aging (vs young) rats has a 60% reduction in mucosal
      blood flow; prominent hypoxia; and increased early growth response-1
      transcription factor and PTEN messenger RNAs, and proteins. It also has increased
      expression of proapoptotic proteins caspase-3 and capase-9, reduced survivin, and
      a 6-fold increased apoptosis vs mucosa of young rats. Ethanol-induced gastric
      mucosal injury in aging (vs young) rats was significantly increased. The down
      regulation of PTEN in gastric mucosa of aging rats completely reversed its
      increased susceptibility to ethanol injury. In aging human gastric mucosa, PTEN
      expression was significantly increased, whereas survivin was significantly
      reduced. CONCLUSIONS: (1) Gastric mucosa of aging rats has significantly reduced
      blood flow, tissue hypoxia, activation of Egr-1, PTEN; increased caspases; and
      reduced survivin. (2) These changes increase susceptibility of aging gastric
      mucosa to injury.

PMID- 18054566
TI  - Severe intestinal obstruction on induced smooth muscle-specific ablation of the
      transcription factor SRF in adult mice.
AB  - BACKGROUND & AIMS: SRF (Serum Response Factor), a widely expressed transcription
      factor, controls expression of mitogen-responsive and muscle-specific genes,
      thereby regulating the contractile actin microfilament. Genetic Srf deletion
      studies showed SRF to be indispensable for in vivo skeletal and cardiac muscle
      cell development. We now investigated for the first time in vivo SRF functions in
      smooth muscle cells of adult mice. METHODS: We conditionally deleted a floxed Srf
      allele (Srf(flex1)) in adult mice by inducible activation of the CreER(T2)
      recombinase expressed specifically in smooth muscle cells. Tamoxifen-induced
      CreER(T2) activity stimulated deletion of exon 1 coding sequences of Srf(flex1),
      thereby abolishing full-length SRF protein expression in adult smooth muscle
      cells of the analyzed organs: colon, bladder, and stomach. RESULTS: Smooth muscle
      cell-specific ablation of full-length SRF protein in adult mice showed impaired
      contraction of intestinal smooth muscle, resulting in defective peristalsis.
      Mutant mice died within 2 weeks of tamoxifen treatment, displaying clear symptoms
      of ileus paralyticus. Cultured primary SRF-deficient colon smooth muscle cells
      were viable, but displayed drastic structural alterations and elevated
      senescence, paralleled by degeneration of the actin microfilament and impaired
      expression of smooth muscle-specific genes. CONCLUSIONS: SRF plays a vital role
      in the contractile activity and cytoskeletal architecture of adult smooth muscle
      cells and is therefore essential for physiologic functions of the
      gastrointestinal tract in vivo. Our mouse genetic model may resemble features of
      human chronic intestinal pseudo-obstruction.

PMID- 18054567
TI  - Inducible mouse model of chronic intestinal pseudo-obstruction by smooth muscle
      specific inactivation of the SRF gene.
AB  - BACKGROUND & AIMS: Serum response factor (SRF) regulates the expression of muscle
      genes and immediate early genes. We investigated the consequences of inactivating
      this transcription factor SRF in adult gastrointestinal smooth muscle cells.
      METHODS: SRF-floxed mice were crossed with SM-CreER(T2)(ki) mice expressing a
      tamoxifen-inducible recombinase in smooth muscle cells. Tamoxifen was injected
      into 12-week-old animals to activate the CreER(T2) and excise the SRF gene.
      RESULTS: SRF was down-regulated in the smooth muscle cells of the
      gastrointestinal tract, urinary bladder, and aorta. The mutant mice developed
      severe dilation of the intestinal tract associated with food stasis and air-fluid
      levels in the lumen 13 days after tamoxifen treatment. Mutant mice displayed
      cachexia and died between days 13 and 22. The dilation was associated with a
      thinning of the muscularis propria and was also observed in the urinary bladder.
      Ex vivo colonic contraction induced by electric field stimulation and carbachol
      was impaired in the mutant mice before the occurrence of the dilation phenotype.
      The expression of several genes, including those encoding smooth muscle actin,
      the heavy chain of smooth muscle myosin, and smoothelin, was 60% to 70% lower in
      mutants than in controls, and mutants also had a lower F/G actin ratio.
      CONCLUSIONS: SRF plays a central role in maintaining visceral smooth muscle
      contractile function in adults. Mice with a smooth muscle cell-specific SRF
      mutation develop a severe motility disorder resembling chronic intestinal pseudo
      obstruction in humans and may be used as an inducible model of this disorder.

PMID- 18054568
TI  - Visceral neuropathy and intestinal pseudo-obstruction in a murine model of a
      nuclear inclusion disease.
AB  - BACKGROUND & AIMS: Intestinal dysmotility is a component of many
      neurodegenerative disorders, including some characterized by neuronal
      intranuclear inclusions. PrP-SCA7-92Q transgenic mice phenocopy many aspects of
      the human polyglutamine neurodegenerative disorder spinocerebellar ataxia type 7
      (SCA7). The enteric neuropathology of PrP-SCA7-92Q mice was investigated after
      observing that they develop signs of intestinal pseudo-obstruction. METHODS:
      Gastrointestinal transit of radio-opaque pellets through presymptomatic and
      symptomatic PrP-SCA7-92Q mice and nontransgenic littermates was compared. Gross,
      microscopic, and ultrastructural studies were conducted, along with histologic
      and whole mount immunohistochemistry, to identify intranuclear inclusions and
      quantify subsets of enteric neurons. Immunoblot analysis was performed to confirm
      selective loss of particular neuronal populations. RESULTS: A subset of
      cholinergic enteric ganglion cells in PrP-SCA7-92Q mice harbor nuclear inclusions
      composed of transgene-derived ataxin-7, which contains a pathogenic polyglutamine
      expansion. These animals die between 15 and 20 weeks of age with intestinal
      distension and enterocolitis. Signs of disease are preceded by selective loss of
      nitric oxide synthase-positive neurons (which lack nuclear inclusions), loss of
      nerve fibers in the myenteric nerve plexus, and delayed gastrointestinal transit.
      Cholinergic neurons, including those with inclusions, are spared. CONCLUSIONS:
      PrP-SCA7-92Q mice may be useful models for human intestinal pseudoobstruction,
      particularly visceral neuropathies with neuronal intranuclear inclusions. Loss of
      inclusion-free inhibitory neurons supports the hypothesis that inclusions may be
      neuroprotective or coincidental, as opposed to harbingers of neuron death.
      Because enteric neuropathology in PrP-SCA7-92Q animals is easily missed by
      routine histopathology, quantitative immunohistochemical approaches may be
      required to recognize analogous forms of human enteric neuropathy.

PMID- 18054569
TI  - Divergent metabolic adaptations to intestinal parasitic nematode infection in
      mice susceptible or resistant to obesity.
AB  - BACKGROUND & AIMS: Diet-induced obesity results from increased ingestion of
      energy-dense food and sedentary lifestyle in genetically susceptible individuals.
      An environmental factor that may have shaped our energy homeostasis throughout
      evolution is parasitic nematode infection. METHODS: To test the hypothesis that a
      metabolically "thrifty phenotype" is advantageous during intestinal nematode
      infection, we compared the responses to Heligmosomoides polygyrus infection
      between 2 mouse strains: obesity-prone C57Bl/6J vs obesity-resistant SWR/J.
      Metabolic phenotyping was performed using indirect calorimetry, dual energy x-ray
      absorptiometry, and magnetic resonance imaging scanning. Gene expression was
      assessed by quantitative reverse-transcription polymerase chain reaction and
      immunohistochemistry. RESULTS: Body weight was maintained in both strains during
      nematode infection via different mechanisms. There was no apparent change in
      energy expenditure between the strains; however, SWR/J mice exhibited a marked
      hyperphagia (calorie intake 60% higher than C57Bl/6J) to maintain body weight.
      The importance of hyperphagia was confirmed by severe weight loss in a group of
      infected SWR/J mice whose food intake was restricted to that of naive mice.
      Furthermore, SWR/J mice expelled nematodes more rapidly than C57Bl/6J mice, an
      effect related to a T helper cell 2 immune response. CONCLUSIONS: C57Bl/6J mice
      are more energy efficient during parasitic nematode infection, which may explain
      their ability to tolerate the infection. SWR/J mice, on the other hand, require
      an increase in food intake to maintain energy stores during nematode infection.
      In addition, a strong T helper cell 2-mediated immune response that facilitates a
      prompt clearance of nematode infection in SWR/J mice may have evolved to conserve
      energy in this strain.

PMID- 18054570
TI  - Prospective identification of a multilineage progenitor in murine stomach
      epithelium.
AB  - BACKGROUND & AIMS: Epithelial stem cells in the stomach are responsible for
      constant renewal of the epithelium through generation of multiple gastric cell
      lineages that populate the gastric glands. However, gastric stem or progenitor
      cells have not been well-characterized because of the lack of specific markers
      that permit their prospective recognition. We identified an intestinal promoter
      that is active in a rare subpopulation of gastric epithelial cells and
      investigated whether these cells possess multilineage potential. METHODS: A
      marked allele of the endogenous mouse villin locus was used to visualize single
      beta-galactosidase-positive cells located in the lower third of antral glands. A
      12.4-kb villin promoter/enhancer fragment drives several transgenes (EGFP, beta
      galactosidase, and Cre recombinase) in these cells in a pattern similar to that
      of the marked villin allele. Reporter gene activity was used to track these cells
      during development and to examine cell number in the context of inflammatory
      challenge while Cre activity allowed lineage tracing in vivo. RESULTS: We show
      that these rare epithelial cells are normally quiescent, but multiply in response
      to interferon gamma. Lineage tracing studies confirm that these cells give rise
      to all gastric lineages of the antral glands. In the embryo, these cells are
      located basally in the stomach epithelium before completion of gastric gland
      morphogenesis. CONCLUSIONS: We have identified a rare subpopulation of gastric
      progenitors with multilineage potential. The ability to prospectively identify
      and manipulate such progenitors in situ represents a major step forward in
      gastric stem cell biology and has potential implications for gastric cancer.

PMID- 18054571
TI  - In vivo lineage tracing defines the role of acinar-to-ductal transdifferentiation
      in inflammatory ductal metaplasia.
AB  - BACKGROUND & AIMS: Chronic injury results in regeneration of normal pancreatic
      tissue and formation of a metaplasia of ductal phenotype. Metaplastic ductal
      lesions are seen in pancreatitis as well as in specimens of pancreatic cancer and
      are thought to represent a condition with increased risk of neoplasia. Acinar-to
      ductal transdifferentiation is thought to be the source of this metaplasia. This
      has been suggested for flat duct-like lesions called tubular complexes and for
      lesions exhibiting a mucinous metaplasia. However, available studies are based on
      interpretation of static data rather than on direct evidence.
      Transdifferentiation from acinar to ductal cells has never been confirmed in the
      adult pancreas. METHODS: Here, we use Cre-loxP-based genetic lineage tracing in
      vivo to investigate whether transdifferentiation of acinar cells contributes to
      regeneration and metaplasia in pancreatitis. RESULTS: The results show that
      transdifferentiation does not play a role in regeneration of normal tissue.
      Acinar cells are regenerated by preexisting acinar cells and not from other cell
      types. Three different types of metaplastic ductal lesions are observed and
      analyzed. Whereas the majority of metaplastic lesions are not of acinar origin,
      acinar-to-ductal transdifferentiation is identified in a minority of mucinous
      metaplastic lesions. CONCLUSIONS: Here, we provide direct evidence that acinar-to
      ductal transdifferentiation occurs in the adult pancreas in vivo. However, it
      accounts for only a minority of metaplastic lesions.

PMID- 18054572
TI  - Bradykinin attenuates hepatocellular damage and fibrosis in rats with chronic
      liver injury.
AB  - BACKGROUND & AIMS: Recent studies have suggested that the kallikrein-kinin system
      regulates tissue fibrogenesis. We hypothesize that bradykinin (BK), the main
      effector peptide of this system, regulates hepatic fibrogenesis. METHODS:
      Kallikrein-kinin system components were studied by quantitative reverse
      transcription polymerase chain reaction analysis, immunohistochemistry, and
      Western blotting. The effect of bradykinin on liver injury was studied by
      infusing saline or bradykinin (1 and 100 ng/kg/min) through a subcutaneous pump
      into carbon tetrachloride-treated rats and mice treated with Fas-stimulating
      antibody. Bradykinin effects were studied in cultured hepatic stellate cells
      (HSCs) and hepatocytes. RESULTS: Bradykinin receptors and kallikrein-1 were
      detected in both normal and fibrotic human livers and HSCs. BK receptors were up
      regulated in fibrotic livers and activated HSCs. Bradykinin infusion reduced
      liver damage, as indicated by decreased aminotransferase serum levels and reduced
      histologic necroinflammatory score without inducing changes in arterial pressure.
      Moreover, bradykinin attenuated hepatic fibrosis, as indicated by reduced
      collagen accumulation, smooth muscle alpha-actin content, as well as decreased
      pro-collagen-alpha1(I) and transforming growth factor-beta1 gene expression.
      Bradykinin infusion reduced hepatocellular apoptosis induced by anti-Fas-receptor
      antibody. HSCs responded to bradykinin with intracellular calcium mobilization.
      Bradykinin reduced procollagen-alpha1(I) and transforming growth factor-beta1
      gene expression and induced matrix metalloproteinase-2 activation. Finally, BK
      induced prosurvival and proliferative intracellular signaling in primary
      hepatocytes. CONCLUSIONS: Bradykinin attenuates liver damage and fibrosis
      development in a rat model of chronic liver injury. Therefore, activation of the
      kallikrein-kinin system may be a new therapeutic approach to the management of
      chronic liver disease.

PMID- 18054573
TI  - How to prevent varices from bleeding: shades of grey--the case for nonselective
      beta blockers.

PMID- 18054574
TI  - Live donor liver transplantation: is it better than waiting?

PMID- 18054575
TI  - A new variable influencing HCV-related liver disease in HIV-HCV coinfected
      individuals?

PMID- 18054576
TI  - Making the case for DCC and UNC5C as tumor-suppressor genes in the colon.

PMID- 18054577
TI  - Colonic neutrophils in inflammatory bowel disease: double-edged swords of the
      innate immune system with protective and destructive capacity.

PMID- 18054578
TI  - Deciphering chronic intestinal pseudo-obstruction: do mice help to solve the
      riddle?

PMID- 18054579
TI  - Metaplastic metamorphoses in the mammalian pancreas.

PMID- 18054580
TI  - How exactly do i diagnose intestinal metaplasia in Barrett's esophagus?

PMID- 18054583
TI  - Beginning to unravel the common, low-penetrance genetic components behind
      colorectal cancer by whole-genome association scans.

PMID- 18054581
TI  - Treating difficult-to-treat hepatitis C virus infection: we may still need to
      push the ribavirin envelope.

PMID- 18054584
TI  - Quality is as important as the quantity: role of mucin glycosylation on
      intestinal barrier function.

PMID- 18054585
TI  - Cytochrome P450 CYP2C9 polymorphism and NSAID-related acute gastrointestinal
      bleeding.

PMID- 18054587
TI  - Impact of CYP2C9 genotype on pharmacokinetics: are all NSAIDs the same?

PMID- 18054589
TI  - Increased intra-abdominal pressure and GERD/Barrett's esophagus.

PMID- 18054591
TI  - The role of hepatic venous pressure gradient in hepatitis C virus compensated
      cirrhosis.

PMID- 18054592
TI  - Pedestrian fatalities, Atlanta Metropolitan Statistical Area and United States,
      2000-2004.
AB  - Motor vehicle crashes killed almost 5,000 pedestrians in 2005 in the United
      States. Pedestrian risk may be higher in areas characterized by urban sprawl.
      From 2000 to 2004, pedestrian fatality rates declined in the United States, but
      the Atlanta metropolitan statistical area did not experience the same decline.
      Pedestrian fatality rates for males, Hispanics, and the 15-34 and 35-54 year age
      groups were higher in Atlanta than in the United States overall. Pedestrian
      safety interventions should be targeted to high-risk populations and localized
      pedestrian settings.

PMID- 18054593
TI  - Aerial lift fall injuries: a surveillance and evaluation approach for targeting
      prevention activities.
AB  - PROBLEM: Work on aerial lift platforms exposes workers to fall hazards. The
      objective of this study was to identify the most common injury scenarios and
      determine current research gaps for addressing fall incidents associated with
      aerial lifts. METHODS: Three databases were searched: Census of Fatal
      Occupational Injuries (CFOI), NIOSH Fatality Assessment and Control Evaluation
      (FACE) reports, and OSHA Incident Investigation Records. RESULTS: The majority of
      falls/collapses/tipovers were within the height-category of 10-29 feet. Tipovers
      comprised 44-46% of boom-lift falls and 56-59% of scissor-lift falls.
      Constructing and repairing activities were most commonly associated with
      fall/collapse/tipover incidents. DISCUSSION: CFOI and OSHA/FACE show convergent
      data, suggesting similar scenarios for aerial lift tipovers. IMPACT ON INDUSTRY:
      The analysis provides the aerial lift industry information to prioritize their
      efforts on aerial lift design.

PMID- 18054594
TI  - Safety culture: analysis of the causal relationships between its key dimensions.
AB  - INTRODUCTION: Several fields are showing increasing interest in safety culture as
      a means of reducing accidents in the workplace. The literature shows that safety
      culture is a multidimensional concept. However, considerable confusion surrounds
      this concept, about which little consensus has been reached. METHOD: This study
      proposes a model for a positive safety culture and tests this on a sample of 455
      Spanish companies, using the structural equation modeling statistical technique.
      RESULTS: Results show the important role of managers in the promotion of
      employees' safe behavior, both directly, through their attitudes and behaviors,
      and indirectly, by developing a safety management system. IMPACT ON INDUSTRY:
      This paper identifies the key dimensions of safety culture. In addition, a
      measurement scale for the safety management system is validated. This will assist
      organizations in defining areas where they need to progress if they wish to
      improve their safety. Also, we stress that managers need to be wholly committed
      to and personally involved in safety activities, thereby conveying the importance
      the firm attaches to these issues.

PMID- 18054595
TI  - Frequency and determinants of recommended workplace violence prevention measures.
AB  - PROBLEM: Limited information exists concerning adoption of workplace violence
      prevention measures by employers and the factors influencing their adoption.
      METHODS: A weighted sample of North Carolina workplaces (n=210) in operation
      January 1994 through March 1998 was used to estimate prevalence of 18 measures
      and identify community and workplace predictors of having >/=5 recommended
      measures. RESULTS: Location in a metropolitan area most strongly predicted
      presence of >/=5 administrative safety measures while a history of workplace
      violence and being in a high crime area were negatively associated. Belonging to
      an industry considered to be high-risk for workplace homicide was most strongly
      associated with having >/=5 environmental safety measures. DISCUSSION: Factors
      influencing high prevalence of violence prevention measures were related to
      business type, violence history, and location. Knowledge of factors influencing
      adoption of recommended workplace violence prevention measures can help tailor
      interventions to diverse industry settings. IMPACT ON INDUSTRY: An important
      contribution to the understanding and mitigation of workplace homicide is
      knowledge of the extent of implementation of recommended workplace violence
      prevention guidelines and factors influencing their adoption. Identifying factors
      that influence the prevalence and adoption of workplace violence safety
      interventions can help to tailor development of interventions to address the
      issue of workplace homicide across diverse industry settings.

PMID- 18054596
TI  - California's graduated driver license law: Effect on teenage drivers' deaths
      through 2005.
AB  - PROBLEM: While many researchers believe Graduated Driver Licensing (GDL) laws
      save lives by imposing restrictions and delayed licensure on drivers under age
      18, longer term effects on older teenagers have not been studied. METHOD: The
      effects of California's strict GDL law on deaths of drivers ages 16-19 were
      analyzed for 1995-2005 using Incidence Rate Ratios (IRR) and Auto-Regressive
      Integrated Moving Average (ARIMA) time series analysis of Fatality Analysis
      Reporting System mortality data. RESULTS: The two methods yielded similar
      results. IRR analysis found California 16-year-old drivers subject to the GDL
      experienced a 15% fatality decline (95% CI, 0.70-0.99), while 18 year-old drivers
      experienced a 15% increase (95% CI, 1.02-1.27). ARIMA analysis found 16 year-old
      drivers experienced a near-significant 20% fatality decline (p=0.07), while 18
      year-olds experienced a 24% increase (p=0.01). Unlicensed teenage drivers and
      older teen drivers driving alone and transporting teenage passengers suffered
      significant fatality increases. SUMMARY AND DISCUSSION: California's GDL may
      negatively affect older teenagers and other driver subpopulations and merits
      reevaluation.

PMID- 18054597
TI  - Assessing regulatory effectiveness with exogenously declining risk: a case study
      of the CPSC's 1973 mattress standard.
AB  - INTRODUCTION: This paper examines the contribution of the U.S. Consumer Product
      Safety Commission's (CPSC) 1973 cigarette ignition mattress flammability standard
      to reduce mattress fires since 1980, when the U.S. Fire Administration's National
      Fire Incident Reporting System became fully operational. METHOD: The paper
      attempts to separate the effect of the cigarette ignition standard from the
      declining trend in mattress fires that would have resulted without the standard.
      We analyze the impact of the 1973 cigarette standard on smoking material ignition
      fires, deaths, and injuries as well as its effect on fires, deaths, and injuries
      from all ignition sources (smoking material ignitions, open-flame ignitions, and
      other ignition sources). Impacts on Industry: The results suggest that the 1973
      mattress standard has effectively reduced the mattress fire risk and that further
      reductions in risk via actions tied specifically to cigarette ignition are likely
      to be difficult to achieve.

PMID- 18054598
TI  - Cannabis use and self-reported collisions in a representative sample of adult
      drivers.
AB  - PROBLEM: This study examines the relationships between collision involvement and
      several measures of cannabis use, including driving after using cannabis, among
      drivers, based on a population survey of Ontario adults in 2002 and 2003. METHOD:
      Logistic regression analyses examined self-reported collision involvement in the
      last 12 months by lifetime use of cannabis, past year use of cannabis, and past
      year driving after using cannabis, while controlling for demographic
      characteristics. RESULTS: We found that the odds of reporting collision
      involvement was significantly higher among cannabis users, and among those who
      reported driving after cannabis use. Some evidence for a dose-response
      relationship was seen as well. DISCUSSION: Cannabis users and people who report
      driving after cannabis use are also more likely to report being involved in a
      collision in the past year. These observations suggest that collision prevention
      efforts could be aimed at these groups. Additional work to determine the causal
      pathways involved in the relationships observed here is needed. IMPACT ON
      INDUSTRY: None.

PMID- 18054599
TI  - Development and initial validation of an Aviation Safety Climate Scale.
AB  - PROBLEM: A need was identified for a consistent set of safety climate factors to
      provide a basis for aviation industry benchmarking. METHOD: Six broad safety
      climate themes were identified from the literature and consultations with
      industry safety experts. Items representing each of the themes were prepared and
      administered to 940 Australian commercial pilots. RESULTS: Data from half of the
      sample (N=468) were used in an exploratory factor analysis that produced a 3
      factor model of Management commitment and communication, Safety training and
      equipment, and Maintenance. A confirmatory factor analysis on the remaining half
      of the sample showed the 3-factor model to be an adequate fit to the data.
      DISCUSSION: The results of this study have produced a scale of safety climate for
      aviation that is both reliable and valid. IMPACT ON INDUSTRY: This study
      developed a tool to assess the level of perceived safety climate, specifically of
      pilots, but may also, with minor modifications, be used to assess other groups'
      perceptions of safety climate.

PMID- 18054600
TI  - Cell phone users, reported crash risk, unsafe driving behaviors and dispositions:
      a survey of motorists in Maryland.
AB  - INTRODUCTION: The purpose of this investigation was to identify risky driving
      behaviors and dispositions that distinguish drivers who use a cell phone while
      operating a motor vehicle from non-cell phone using drivers. METHOD: Annual
      telephone surveys were used to identify drivers who reported using a cell phone
      while driving in the last month (n=1803) and were compared to those who said they
      did not use cell phones while driving (n=1578). RESULTS: Cell phone using drivers
      were more likely to report driving while drowsy, going 20 mph over the speed
      limit, driving aggressively, running a stop sign or red light, and driving after
      having had several drinks. They were also more likely to have had a prior history
      of citation and crash involvement than non-cell phone using drivers. Cell phone
      using drivers also reported they were less careful and more in a hurry when they
      drive than non-cell phone using drivers. CONCLUSION: Cell phone using drivers
      report engaging in many behaviors that place them at risk for a traffic crash,
      independent of the specific driving impairments that cell phone usage may
      produce. Strategies that combine coordinated and sustained enforcement activities
      along with widespread public awareness campaigns hold promise as effective
      countermeasures for these drivers, who resemble aggressive drivers in many
      respects.

PMID- 18054601
TI  - The deterrent effect of increasing fixed penalties for traffic offences: the
      Norwegian experience.
AB  - PROBLEM: Many motorized countries use fixed penalties to deter the most common
      traffic violations. Fixed penalties are usually given at the spot by a police
      officer. If the offender accepts the fixed penalty, no court hearing or trial is
      held. During the years 1995-2004, the rates for fixed penalties for traffic
      offences in Norway increased substantially. This paper evaluates the effects on
      compliance of these increases. METHOD: Regression analysis was performed to
      determine the effects of increases in fixed penalties. RESULTS: For speeding in
      general, no effect of increasing fixed penalties can be found. For speeding close
      to speed camera sites, there is a weak tendency for the violation rate to go
      down. This tendency is not statistically significant at conventional levels. For
      seat belt wearing, wearing rates are found to increase as fixed penalties have
      increased. In recent years, however, enforcement of the seat belt law has stepped
      up, making it impossible to separate the effect of enforcement from that of fixed
      penalties. IMPACT ON INDUSTRY: It has been suggested that the police may adapt to
      stricter penalties by reducing enforcement or by adopting larger tolerance
      margins for violations. Available evidence does not support this hypothesis.

PMID- 18054602
TI  - Age of licensure and monitoring teenagers' driving: survey of parents of novice
      teenage drivers.
AB  - OBJECTIVE: To assess parental decision making regarding the timing of teenagers
      initiating driving and monitoring teenagers' driving after licensure. METHODS:
      About 300 parents were interviewed during spring 2006 in Minnesota, North
      Carolina, and Rhode Island, states with varying licensing provisions, while
      teenagers took their first on-road driving tests. RESULTS: States' differences in
      ages of obtaining learner's permits and licenses reflected different licensing
      laws, but most teenagers obtained permits and took road tests within the first
      few months after they became eligible. Common reasons for delaying obtaining
      permits were fulfilling driver education requirements and lack of
      readiness/immaturity. Insufficient practice driving most often delayed licensure.
      Among the parents interviewed, 33-49% believed the minimum licensure age should
      be 17 or older. Almost all parents planned to supervise teenagers' driving after
      licensure, and most wanted to know about speeding or distractions. When asked
      about in-vehicle devices to monitor teenagers' driving, 37-59% of parents had
      heard of them. Parents were least interested in using video cameras and about
      equally interested in computer chips and cell-phone-based GPS systems.
      Disinterest in monitoring devices most often was attributed to trusting teenagers
      or respecting their privacy. CONCLUSIONS: Licensing laws influence ages of
      initiating driving. Although many parents support licensing at 17 or older -
      higher than in all but one state - most teenagers initiate driving soon after
      reaching the minimum age. Parents plan to supervise teenagers' driving, and many
      say they are open to using in-vehicle monitoring devices. IMPACT ON INDUSTRY:
      Many parents support a minimum licensing age of 17 or older and would consider in
      vehicle devices to extend their supervision of teenager's driving.

PMID- 18054603
TI  - Choice of teenagers' vehicles and views on vehicle safety: survey of parents of
      novice teenage drivers.
AB  - OBJECTIVE: To examine parental decisions about vehicles driven by teenagers and
      parental knowledge of vehicle safety. METHODS: About 300 parents were interviewed
      during spring 2006 in Minnesota, North Carolina, and Rhode Island while teenagers
      took their first on-road driving tests. RESULTS: Fewer than half of parents
      surveyed said teenagers would be the primary drivers of the chosen vehicles.
      Parents most often cited safety, existing family vehicle, and reliability when
      explaining the choices for their teenagers' vehicles. About half of the vehicles
      intended for teenagers were small/mini/sports cars, pickups, or SUVs - vehicles
      considered less safe for teenagers than midsize/large cars or minivans. A large
      majority of vehicles were 2001 models or earlier. Vehicles purchased in
      anticipation of adding a new driver to the family were more likely to be the
      sizes/types considered less safe than vehicles already owned. Few parents
      insisted on side airbags or electronic stability control, despite strong evidence
      of their safety benefits. Even when asked to identify ideal vehicles for their
      teenagers to drive, about half of parents identified less safe vehicle
      sizes/types. Most parents knew that midsize/large vehicles are safer than small
      vehicles, and at least half of parents said SUVs and pickups are not safe for
      teenage drivers, citing instability. CONCLUSIONS: The majority of parents
      understood some of the important criteria for choosing safe vehicles for their
      teenagers. However, parents actually selected many vehicles for teenagers that
      provide inferior crash protection. IMPACT ON INDUSTRY: Vehicle safety varies
      substantially by vehicle size, type, and safety features. Many teenagers are
      driving inferior vehicles in terms of crashworthiness and crash avoidance.

PMID- 18054606
TI  - Success and complication rates of endoscopic third ventriculostomy for adult
      hydrocephalus: a series of 108 patients.
AB  - BACKGROUND: The clinical response to ETV of adult patients with noncommunicating
      hydrocephalus may differ from that of children because of such factors as
      chronicity of hydrocephalus, physiologic differences in CSF dynamics, and changes
      in brain viscoelastic properties. We sought to determine which factors might
      predict clinical success and failure. METHODS: A retrospective single-surgeon
      case series analysis was performed. This was a consecutive case series for which
      the goal of the ETV procedures was shunt independence. One hundred ten ETV
      procedures were performed in 108 adult patients (mean, 48 years; range, 17-88
      years). There were 52 cases of idiopathic aqueductal stenosis, 47 cases of mass
      lesions causing noncommunicating hydrocephalus, plus 9 other miscellaneous
      obstructive etiologies. RESULTS: Long-term shunt independence was achieved in 77%
      of patients. Two additional patients, who initially failed, later achieved
      success after reoperation and remained shunt free for the duration of their
      follow-up. Therefore, after reoperation, shunt independence was achieved in 79%
      of patients. Of the patients who ultimately failed, 11 failed within 1 month.
      Therefore, 52% who ultimately failed had more than 1 month of shunt-free
      existence (mean, 10 months). There were 6 surgical complications, including 2
      deaths related to intracranial hemorrhage from brain tumors (not directly related
      to ETV per se), and 10 medical complications. The median hospital length-of-stay
      was 3 days. The median follow-up was 8 months (range, 0-95 months). CONCLUSIONS:
      Endoscopic third ventriculostomy is an effective treatment option for adult
      patients with noncommunicating hydrocephalus. Although most procedures resulted
      in long-term shunt independence, more than half of the eventual failures were
      delayed, and therefore, appropriate follow-up is required.

PMID- 18054607
TI  - Efficacy of different bone volume expanders for augmenting lumbar fusions.
AB  - BACKGROUND: A wide variety of bone volume expanders are being used in performing
      posterolateral lumbar noninstrumented and instrumented lumbar fusions. This
      article presents a review of their efficacy based on fusion rates, complications,
      and outcomes. METHODS: Lumbar noninstrumented and instrumented fusions frequently
      use laminar autografts and different bone graft expanders. This review presents
      the utility of multiple forms/ratios of DBMs containing allografts. It also
      discusses the efficacy of artificial bone graft substitutes, including HA and B
      TCP. Dynamic x-ray and/or CT examinations were used to document fusion in most
      series. Outcomes were variously assessed using Odom's criteria or different
      outcome questionnaires (Oswestry Questionnaire, SF-36, Dallas Pain Questionnaire,
      and/or Low Back Pain Rating Scale). RESULTS: Performing noninstrumented and
      instrumented lumbar posterolateral fusions resulted in comparable fusion rates in
      many series. Similar outcomes were also documented based on Odom's criteria or
      the multiple patient-based questionnaires. However, in some studies, the addition
      of spinal instrumentation increased the reoperation rate, operative time, blood
      loss, and cost. Various forms of DBMs, applied in different ratios to autografts,
      effectively supplemented spinal fusions in animal models and patient series. beta
      Tricalcium phosphate, which is used to augment autograft fusions addressing
      idiopathic scoliosis or lumbar disease, also proved to be effective. CONCLUSIONS:
      Different types of bone volume expanders, including various forms of allograft
      based DBMs, and artificial bone graft substitutes (HA and B-TCP) effectively
      promote posterolateral lumbar noninstrumented and instrumented fusions when added
      to autografts.

PMID- 18054609
TI  - Mini-open anterior approach for corpectomy in the thoracolumbar spine.
AB  - BACKGROUND: Traditional open anterior approaches to the TL spine were reported
      with a significant morbidity from a large wound field; therefore, "minimally
      invasive" thoracoscopic and laparoscopic anterior approaches have been recently
      introduced. However, these endoscopic techniques require a long and steep
      learning curve, require expensive disposable endoscopy material, and may be
      little suited for complication management. Alternatively, "mini-open" anterior
      approaches with table-mounted retractor systems have also been recently
      introduced. METHODS: Thirty-seven patients underwent a single-level thoracic or
      lumbar corpectomy and cage reconstruction for an unstable traumatic burst
      fracture or vertebral body tumor. A transthoracic (n = 6), transthoracic
      transdiaphragmatic (n = 23), or retroperitoneal (n = 8) mini-open approach was
      conducted with the SynFrame (Stratec Medical, Oberdorf, Switzerland) table
      mounted retractor. Prior posterior pedicle screw fixation was performed in 35 of
      37 patients. RESULTS: The mean surgical duration of the anterior approach was 181
      minutes, and the average blood loss was 632 mL. There was no neurological
      worsening. On a VAS from 0 to 10, the mean local pain from the anterior approach
      was 1.7 at 6 months postoperatively, 1.4 at 12 months, and 1.0 at 24 months.
      Construct stability was found in all patients at 6 months after surgery. Six
      transient complications occurred. CONCLUSIONS: The mini-open anterior approach
      for corpectomy in the TL spine is safe, reliable, and economical. The table
      mounted SynFrame retractor provides a stable operating field through which a
      familiar direct 3-dimensional view of the anterior TL spine is obtained with
      limited approach morbidity. This technique is an excellent alternative to
      thoracoscopic or laparoscopic procedures, avoiding the steep learning curve,
      technical difficulties, and equipment costs of endoscopic procedures.

PMID- 18054611
TI  - Magnesium sulfate in the management of patients with aneurysmal subarachnoid
      hemorrhage: a randomized, placebo-controlled, dose-adapted trial.
AB  - BACKGROUND: Recent studies suggest that high-dose MgSO4 therapy is safe and
      reduces the incidence of DIND and subsequent poor outcome after SAH. We intended
      to assess the safety and efficacy of high-dose MgSO4 therapy after SAH as means
      to prevent DIND and to evaluate the impact on clinical outcome. METHODS: This was
      a prospective, randomized, single-blind, placebo-controlled study. The MgSO4
      infusion was adjusted every 12 hours until day 12 according to the target serum
      Mg2+ level. The occurrence of DIND, secondary infarction, side effects, and the
      outcome after 3 and 12 months were assessed. RESULTS: Fifty-eight patients were
      randomized; 27 received placebo and 31 MgSO4. The difference in occurrence of
      DIND and secondary infarction was not significant. The intention-to-treat
      analysis revealed a trend toward better outcome (P = .083) after 3 months. On
      treatment analysis showed a significantly better outcome after 3 months (P =
      .017) and a trend toward better outcome after 1 year (P = .083). Significantly
      more often hypotension (P = .040) and hypocalcemia (P = .005) occurred as side
      effects in the treatment group. In 16 patients (52%), the MgSO4 therapy had to be
      stopped before day 12 because of side effects. No predictive factor leading to
      termination was found in a postrandomization analysis. CONCLUSIONS: High-dose
      MgSO4 therapy might be efficient as a prophylactic adjacent therapy after SAH to
      reduce the risk for poor outcome. Nevertheless, because of the high frequency of
      the side effects, patients should be observed in an intensive or intermediate
      care setting.

PMID- 18054613
TI  - Multivariate analysis of risk factors of hematoma expansion in spontaneous
      intracerebral hemorrhage.
AB  - BACKGROUND: We focused on the cause of hematoma expansion after admission because
      the volume of hematoma after S-ICH plays a crucial role in the cause of mortality
      and morbidity. METHODS: In a retrospective review, 51 patients with hematoma
      expansion of S-ICH were identified among 880 cases of S-ICH treated between 2001
      and May 2006. We divided cases into 2 groups according to the time of hematoma
      expansion. An enlargement of hematoma within 2 weeks after hospitalization was
      categorized as the acute stage group and after 2 weeks was categorized as the
      chronic stage group. Spontaneous intracerebral hemorrhage without hematoma
      expansion group (100 cases) had been consecutively selected as a control group.
      We analyzed the risk factors of hematoma expansion in patients with S-ICH
      especially in the acute stage group. RESULTS: Fifty-one of 880 patients had the
      enlargement of hematoma (5.8%). Forty-three (84%) of 51 cases were acutely
      developed and 8 cases (16%) were developed chronically. On univariate analysis
      there were significant differences in BP within the initial 48 hours (P < .0001),
      GOS (P < .0001), and previously taking anticoagulant agents (P = .0053).
      Especially the difference in SBP and DBP within 48 hours between groups was 19
      (11%) and 13 mm Hg (14%), respectively. The DBP within the initial 24 hours had a
      meaningful odds ratio (1.06) on logistic regression analysis. CONCLUSION: A
      reduction of BP by 15% (SBP < or =140 mm Hg, DBP < or =80 mm Hg) is necessary at
      acute stage in S-ICH.

PMID- 18054615
TI  - Pilot trial of the rate of response, safety, and tolerability of temozolomide and
      oral VP-16 in patients with recurrent or treatment-induced malignant central
      nervous system tumors.
AB  - BACKGROUND: The aim of this study was to determine the response and toxicity of
      patients with recurrent or treatment-induced brain tumors to TMZ and oral VP-16.
      METHODS: Eleven patients with recurrent or treatment-induced malignant CNS
      tumors, including treatment-induced PNET (in 1 patient), brainstem glioma (in 3
      patients; 1 with treatment-induced, 2 with recurrence), recurrent anaplastic
      astrocytoma (in 3 patients), and recurrent glioblastoma (in 4 patients) were
      evaluated in a pilot study of TMZ and oral VP-16 chemotherapy. All patients
      received TMZ at 150 mg/m2 per day on days 1 to 5 and oral VP-16 at 50 mg/m2 per
      day on days 1 to 12. Cycles were repeated every 28 days. RESULTS: None
      experienced major acute toxicity related to TMZ and oral VP-16 during a total of
      52 treatment courses. Five (45%) of 11 patients showed a PR to treatment. Among
      the 11 patients enrolled, 7 patients are alive with disease at a median of 9
      months from time of study entry. The 6-month PFS is 45% (95% CI, 40%-74%). The
      histologic subtype of the tumor, its location, and its maximum response to
      chemotherapy did not have an impact on the duration of disease control.
      CONCLUSION: This limited pilot study confirms the innocuousness and the activity
      of the combination of TMZ and oral VP-16 in recurrent malignant brain tumors.
      This promising activity warrants further investigation of this combination in
      larger phase II or III studies.

PMID- 18054616
TI  - Cognitive function of patients with brain tumor in pre- and postoperative stage.
AB  - BACKGROUND: Nobody knows whether cognitive dysfunction affects survival.
      Furthermore, it is unknown whether the dysfunction is caused by the tumor itself
      or by its treatment. METHODS: Patients with 20 gliomas (LGG, 7; MG, 13 [AG, 4;
      GM, 9]) in the right brain (nondominant) and 11 gliomas (LGG, 1; MG, 10 [AG, 6;
      GM, 4]) in the left brain (dominant) were studied. Thirty-four patients with
      meningioma were also studied. Cognitive function was evaluated by the 3MS
      examination, and propriety of radical resection of tumor was reviewed. RESULTS:
      Cognitive function pre-Op and post-Op was normal in patients with LGG and MGs in
      the right brain but decreased before an Op in all patients with MG in the left
      brain, and they did not normalize after Op. In patients with MG in left brain,
      the test of temporal and spatial orientation, first recall, similarities, 4
      legged animals, mental reversal, and writing decreased after Op. Cognitive
      hypofunction before or after Op did not correlate with tumor malignancy and
      degree of tumor resection. CONCLUSION: Firstly, radical Op should aim at
      improvement of cognitive function for patients with glioma in the right brain,
      and for patients with glioma in the left brain, QOL should be thought about
      without expecting improvement of cognitive function. Secondly, improvement of
      cognitive function cannot be anticipated in patients with meningioma in the left
      brain. Aged patients older than 75 years require carefulness in Op. Then, damage
      of the cingulated gyrus and corpus callosum should be avoided in the left brain.
      This study emphasizes that clinicians should be careful in the evaluation of
      cognitive function in glioma and meningioma treatment.

PMID- 18054618
TI  - Diffusion magnetic resonance imaging as an evaluation of the response of brain
      metastases treated by stereotactic radiosurgery.
AB  - BACKGROUND: Loss of tumor cell results in a relative increase in extracellular
      space that may lead to alteration of ADC. Our purpose was to see if the ADC could
      be used, rather than methods depending on changes in tumor size, to predict
      treatment success after treatment of brain metastases with SRS. METHODS: In a
      prospective study, the ADCs of 21 patients with 32 solid or solid-dominated brain
      metastases were taken before and 1 week, 1 month, and at 3-month intervals after
      SRS. Mean ADC values at the various time intervals were compared with each other
      to see whether or not the ADC might be used as an early indicator of treatment
      success or failure. RESULTS: The mean pretreatment value of the ADC in the
      metastatic tumors was 1.05 +/- 0.12 x 10(-3) mm2/s (mean +/- SD). This value for
      the tumors rose significantly (P = .009) 7 days after SRS and continued to rise
      with time. Magnetic resonance imaging showed that 91% of these tumors had been
      controlled by the SRS. The ADC values in cystic/necrotic tumor tissue (2.13 +/-
      0.18 x 10(-3) mm2/s) were significantly (P < .001) higher than those in
      noncentral necrotic tumor tissue (1.61 +/- 0.14 x 10(-3) mm2/s). CONCLUSIONS: The
      ADC values might eventually be useful to evaluate treatment success-and in some
      patients, detected even at early time points-and to distinguish radiation-induced
      central necrosis from tumor regrowth in cases where other imagery is not
      definitive.

PMID- 18054619
TI  - Nonshaved cranial surgery in black Africans: a short-term prospective preliminary
      study.
AB  - BACKGROUND: Many studies on white populations have shown the absence of any
      scientific, or even beneficial, basis for the traditional preoperative ritual of
      shaving the operative field. We were not able to lay our hands on any document
      regarding this subject on any black African population. METHODS: We prospectively
      performed 17 cranial procedures in nonshaved fields in 15 selected black Africans
      in the Lagos State University Teaching Hospital, Ikeja, Nigeria. RESULTS: There
      was no serious complication recorded over a short-term follow-up of 2 to 6
      months. The short, curly, crimpy, and densely knotted black African scalp hairs
      however did pose some unique perioperative challenges to us. CONCLUSIONS:
      Nonshaved cranial surgery, as in whites/Asians, can also be safely carried out in
      black Africans. This however demands some attention to details in the
      perioperative care of the incision sites. We found this caveat to be particularly
      more imperative in black Africans because of their unique anthropological scalp
      hair characteristics.

PMID- 18054621
TI  - Reconstruction of the sellar dura in transsphenoidal surgery using an expanded
      polytetrafluoroethylene dural substitute.
AB  - BACKGROUND: The transsphenoidal approach for resecting pituitary tumors has
      classically included reconstruction of the anterior wall of the sella turcica. A
      variety of materials have been used in this process for the purpose of both
      recreating the original anatomy and preventing postoperative cerebrospinal fluid
      (CSF) leaks. We studied the use of an ePTFE dural substitute (GORE Preclude MVP,
      W.L. Gore & Associates, Flagstaff, Arizona, USA), as a method for obtaining
      reliable reconstruction of the sellar dura. METHODS: A prospective alternate case
      trial was designed to assess this new dural substitute wherein 60 patients who
      underwent transsphenoidal surgical resection of intrasellar lesions larger than 1
      cm were included. Thirty patients had the sellar dura closed with ePTFE dural
      substitute, whereas 30 patients underwent anterior wall reconstruction as
      ordinarily performed in our institution. RESULTS: Each patient was reassessed at
      closure, and the operative site and sphenoid sinus were evaluated with 3-months
      postoperative magnetic resonance imaging. Three patients experienced
      postoperative CSF leaks: 1 with ePTFE dural substitute and 2 without. All 3
      patients underwent a second operation to repair the CSF leak, without further
      complications. No other postoperative complications were noted in the series.
      CONCLUSION: Expanded polytetrafluoroethylene dural substitute provides a safe and
      effective adjunctive method for reconstruction of the sellar dura.

PMID- 18054623
TI  - Temporal bone dissection for neurosurgery residents: identifying the essential
      concepts and fundamental techniques for success.
AB  - BACKGROUND: Many contemporary neurosurgery residents, cordoned by work hour
      restrictions and drawn to newer technologies such as endovascular therapy, lack
      the proper direction necessary to learn the essentials of temporal bone
      dissection. A thorough knowledge of temporal bone anatomy combined with guidance
      regarding proper surgical technique makes temporal bone dissection an efficacious
      and fundamental learning activity. There is currently no concise guide for
      neurosurgical training programs to use in teaching the essentials of this
      dissection. METHODS: Over several years, the authors worked with neurosurgery
      residents to determine the key concepts necessary to gain a fundamental working
      knowledge of temporal bone dissection. RESULTS: We have identified 5 essential
      surgical principles and developed a step-by-step dissection technique useful for
      neurosurgery residents. CONCLUSIONS: Using this template, neurosurgery residents
      can make the most of their time in the skull base laboratory, becoming familiar
      with relevant temporal bone anatomy in situ and becoming facile with the surgical
      techniques necessary for its safe dissection.

PMID- 18054625
TI  - Neuroscience and the law.

PMID- 18054627
TI  - The challenge for neurosurgery in the 21st century.

PMID- 18054628
TI  - Conus cavernoma: a rare cause of spontaneously resolving paraplegia.

PMID- 18054630
TI  - Evaluation of a computer-based system for plus disease diagnosis in retinopathy
      of prematurity.
AB  - OBJECTIVE: To measure accuracy and reliability of the computer-based Retinal
      Image Multiscale Analysis (RISA) system compared with those of recognized
      retinopathy of prematurity (ROP) experts, for plus disease diagnosis. DESIGN:
      Evaluation of diagnostic test or technology. PARTICIPANTS: Eleven recognized ROP
      experts and the RISA image analysis system interpreted a set of 20 wide-angle
      retinal photographs for presence of plus disease. METHODS: All experts used a
      secure Web site to review independently 20 images for presence of plus disease.
      Images were also analyzed by measuring individual computer-based system
      parameters (integrated curvature [IC], diameter, and tortuosity index) for
      arterioles and venules and by computing linear combinations and logical
      combinations of those parameters. Performance was compared with a reference
      standard, defined as the majority vote of experts. MAIN OUTCOME MEASURES:
      Diagnostic accuracy was measured by calculating sensitivity, specificity, and
      receiver operating characteristic area under the curve (AUC) for plus disease
      diagnosis by each expert, and by each computer-based system parameter, compared
      with the reference standard. Diagnostic agreement was measured by calculating the
      mean kappa value of each expert compared with all other experts and the mean
      kappa value of each computer-based system parameter compared with all experts.
      RESULTS: Among the 11 experts, sensitivity ranged from 0.167 to 1.000,
      specificity ranged from 0.714 to 1.000, AUC ranged from 0.798 to 1.000, and mean
      kappa compared with all other experts ranged from 0.288 to 0.689. Among
      individual computer system parameters, arteriolar IC had the highest diagnostic
      accuracy, with sensitivity of 1.000; specificity, 0.846; and AUC, 0.962.
      Arteriolar IC had the highest diagnostic agreement with experts, with a mean
      kappa value of 0.578. CONCLUSIONS: A computer-based image analysis system has the
      potential to perform comparably to recognized ROP experts for plus disease
      diagnosis.

PMID- 18054631
TI  - Sutureless 25-gauge vitrectomy: risky or rewarding?

PMID- 18054632
TI  - Changes in corneal topography after 25-gauge transconjunctival sutureless
      vitrectomy versus after 20-gauge standard vitrectomy.
AB  - PURPOSE: To evaluate the changes in regular and irregular corneal astigmatism
      after 25-gauge transconjunctival sutureless vitrectomy and 20-gauge standard
      vitrectomy. DESIGN: Prospective observational comparative case series.
      PARTICIPANTS: Thirty-two eyes of 32 patients undergoing 25-gauge
      transconjunctival sutureless vitrectomy and 25 eyes of 24 patients undergoing 20
      gauge standard vitrectomy. METHODS: Corneal topography was obtained
      preoperatively and at 2 weeks and 1 month postoperatively. MAIN OUTCOME MEASURES:
      The dioptric data of the central 3-mm zone of the cornea were decomposed using
      Fourier harmonic analysis into spherical power, regular astigmatism, asymmetry,
      and higher-order irregularity. RESULTS: None of the 4 Fourier indices changed
      throughout the observation period in the 25-gauge group. In the 20-gauge group,
      regular astigmatism, asymmetry, and higher-order irregularity were increased
      significantly at 2 weeks after vitrectomy (P<0.05, Wilcoxon signed-ranks test)
      and returned to preoperative levels by 1 month. The spherical power in the 20
      gauge group did not change after surgery. For regular astigmatism, asymmetry, and
      higher-order irregularity, the 20-gauge group showed significantly greater
      surgically induced changes than the 25-gauge group (P<0.05, Mann-Whitney U test).
      CONCLUSIONS: Twenty-five-gauge transconjunctival sutureless vitrectomy does not
      induce significant changes in corneal topography and exerts little influence on
      the optical quality of the cornea.

PMID- 18054633
TI  - Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment:
      a prospective randomized multicenter clinical study.
AB  - OBJECTIVE: To compare scleral buckling surgery (SB) and primary pars plana
      vitrectomy (PPV) in rhegmatogenous retinal detachments of medium complexity.
      DESIGN: Prospective randomized multicenter clinical trial (the Scleral Buckling
      versus Primary Vitrectomy in Rhegmatogenous Retinal Detachment Study), separated
      into phakic or aphakic/pseudophakic eyes. Patients were enrolled over a 5-year
      period. There was 1-year follow up in the study, and the primary outcome was
      assessed at 1 year. PARTICIPANTS: Forty-five surgeons (25 centers, 5 European
      countries) recruited 416 phakic and 265 pseudophakic patients. Completion of
      follow-up was achieved in 93% of the phakic and 89% of the pseudophakic patients.
      INTERVENTION: Scleral buckling surgery with the potential use of multiple
      sponges, encircling elements, drainage, and intraocular injections. Primary
      vitrectomy included 3-port vitrectomy with sulfur hexafluoride-air tamponade;
      additional SB was left to the surgeon's decision. MAIN OUTCOME MEASURES: Primary
      study end point: change in best-corrected visual acuity (BCVA); secondary end
      points: primary and final anatomical success, proliferative vitreoretinopathy,
      cataract progression, and number of reoperations. RESULTS: In the phakic trial,
      the mean BCVA change was significantly (P = 0.0005) greater in the SB group (SB, 
      0.71 logarithm of the minimum angle of resolution [logMAR], standard deviation
      [SD] 0.68; PPV, -0.56 logMAR, SD 0.76). In the pseudophakic trial, changes in
      BCVA showed a nonsignificant difference of 0.09 logMAR. In phakic patients,
      cataract progression was greater in the PPV group (P<0.00005). In the
      pseudophakic group, the primary anatomical success rate (defined as retinal
      reattachment without any secondary retina-affecting surgery; SB, 71/133 [53.4%];
      PPV, 95/132 [72.0%]) was significantly better (P = 0.0020), and the mean number
      of retina-affecting secondary surgeries (SB, 0.77, SD 1.08; PPV, 0.43, SD 0.85)
      was lower (P = 0.0032) in the PPV group. Redetachment rates were 26.3% (SB;
      55/209) and 25.1% (PPV; 52/207) in the phakic trial and 39.8% (SB; 53/133) and
      20.4% (PPV; 27/132) in the pseudophakic trial. CONCLUSIONS: The study shows a
      benefit of SB in phakic eyes with respect to BCVA improvement. No difference in
      BCVA was demonstrated in the pseudophakic trial; based on a better anatomical
      outcome, we recommend PPV in these patients.

PMID- 18054634
TI  - Endogenous erythroid colony formation in patients with retinal vein occlusion.
AB  - PURPOSE: The pathophysiology and causes of retinal vein occlusion (RVO) remain
      largely unknown. Latent forms of myeloproliferative disorders, which are
      diagnosed by the presence of in vitro endogenous erythroid colony (EEC)
      formation, are a well-known cause of intraabdominal vein thrombosis. The
      suspected diagnosis of a latent myeloproliferative disorder in a patient with
      RVO, based on the presence of EEC formation, led us to evaluate the association
      between latent myeloproliferative disorders and RVO. DESIGN: Observational case
      series in a national eye center. PARTICIPANTS: Forty-four patients, with a mean
      age of 46 years (range, 21-62) and central (n = 38) or peripheral (n = 6) RVO
      responsible for visual acuity decreased to 6/12 or less. METHODS: In vitro bone
      marrow culture. MAIN OUTCOME MEASURE: Endogenous erythroid colony formation in
      cytokine-free culture medium. Conventional diagnostic criteria for
      myeloproliferative disorders and the JAK2 V617F mutation (which is strongly
      associated with myeloproliferative disorders) were assessed in RVO patients
      showing EECs. RESULTS: Endogenous erythroid colony formation was observed in 12
      of 44 (27%) patients with RVO, 13 of 35 (37%) patients with Budd-Chiari syndrome,
      and 52 of 53 (98%) patients with primary polycythemia (positive control groups)
      but not in 22 healthy bone marrow donors (negative controls) evaluated at the
      same time and by the same hematology laboratory. Neither conventional nor genetic
      diagnostic criteria for myeloproliferative disorders were observed in any patient
      with both RVO and an EEC at the time of diagnosis or during follow-up.
      CONCLUSIONS: Endogenous erythroid colony formation is frequently observed in
      patients with RVO independently of any detectable myeloproliferative disorder.
      This opens a new aspect of research on the pathophysiology of this sight
      threatening disease.

PMID- 18054635
TI  - Association of complement factor H and LOC387715 genotypes with response of
      exudative age-related macular degeneration to intravitreal bevacizumab.
AB  - PURPOSE: To investigate whether there is an association between complement factor
      H (CFH) or LOC387715 genotypes with response to treatment with intravitreal
      bevacizumab for exudative age-related macular degeneration (AMD). DESIGN:
      Retrospective cohort study. PARTICIPANTS: The study cohort consisted of 86
      patients being treated for neovascular AMD with bevacizumab alone. METHODS:
      Genotype determination for the CFH Y402H and LOC387715 A69S polymorphisms was
      performed by allele-specific digestion of polymerase chain reaction products. All
      patients were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals
      until choroidal neovascularization was no longer active. MAIN OUTCOME MEASURES:
      CFH Y402H and LOC387715 A69S polymorphisms. Choroidal neovascular lesion
      characteristics were ascertained by fluorescein angiography. Snellen visual
      acuity (VA) was measured before and after treatment. RESULTS: For the CFH Y402H
      polymorphism, patients with the CFH TT genotype had the largest choroidal
      neovascular lesions (P = 0.02). With treatment, VA improved from 20/248 to 20/166
      for the CFH TT genotype and from 20/206 to 20/170 for the TC genotype, but fell
      from 20/206 to 20/341 for the CFH CC genotype (P = 0.016). Only 10.5% of patients
      with the CFH CC genotype demonstrated improved VA with treatment, compared with
      53.7% of CFH TT and TC genotypes (P = 0.004). For the LOC387715 A69S variant,
      patients with the TT genotype had the largest choroidal neovascular lesions (P =
      0.012). There was no significant difference in response to bevacizumab treatment
      according to LOC387715 genotype. CONCLUSIONS: The AMD-associated CFH Y402H and
      LOC387715 A69S variants were associated with differences in choroidal neovascular
      lesion size in this study. Patients with the CFH CC genotype fared significantly
      worse with intravitreal bevacizumab than did those with the CFH TC and TT
      genotypes, suggesting a potential pharmacogenetic relationship. Prospective
      studies to confirm or refute this observation should be considered.

PMID- 18054636
TI  - Annual rates of arterial thromboembolic events in medicare neovascular age
      related macular degeneration patients.
AB  - PURPOSE: Smoking, age, and nutrition have been associated with the development of
      neovascular age-related macular degeneration (AMD) and can increase the risk of
      arterial thromboembolic events (ATEs). This study assesses annual rates of ATEs
      in new-onset neovascular AMD patients compared with matched controls. DESIGN:
      Retrospective study. PARTICIPANTS: New-onset neovascular AMD patients and age-,
      race-, gender-, and database length-matched controls from the 5% Medicare
      database. METHODS: We conducted a retrospective analysis of the 5% Medicare
      database from 2001 to 2003. New-onset neovascular AMD patients were included if
      they were > or =65 years old, had 2 diagnoses of neovascular AMD, and had at
      least 1 year of data before the first diagnosis of AMD within the dataset. A
      control group was constructed in a 3:1 ratio from those without a diagnosis of a
      major eye disorder and matched by age, race, gender, and length of data. Annual
      prevalence rates were determined for myocardial infarctions (MIs) and ischemic
      cerebral vascular accidents (CVAs). MAIN OUTCOME MEASURES: Rates of MIs and
      ischemic CVAs in new-onset neovascular AMD patients and matched controls from
      2001 to 2003. RESULTS: There were 15771 new-onset neovascular AMD patients
      identified and matched with 46 408 controls. Average age was 80.5 years, with 64%
      > or =80; 65% were female; and 95.9% were white. Inpatient MI rates for
      neovascular AMD patients and controls were 2.2% and 2.2%, respectively (P =
      0.74). Inpatient ischemic CVA rates for neovascular AMD patients and controls
      were 3.5% and 3.6%, respectively (P = 0.59). Myocardial infarction rates and
      ischemic CVA rates for both groups increased with age. Subgroups of patients with
      comorbidities known to be risk factors for ATEs (i.e., hypertension,
      hyperlipidemia, diabetes, and arrhythmias) had a higher rate of events. Patients
      with previous ATEs were also at a higher risk of subsequent events, at 7.4% for
      inpatient MI and 35.1% for inpatient ischemic stroke. CONCLUSION: Despite the
      shared risk factors associated with neovascular AMD and ATEs, Medicare
      beneficiaries with neovascular AMD had a rate of ATEs similar to that of matched
      controls. Rates of ATEs increased in patients with comorbidities and for patients
      with previous events.

PMID- 18054637
TI  - Pharmacokinetics of intravitreal ranibizumab (Lucentis).
AB  - PURPOSE: To describe the pharmacokinetics of 0.5 mg of intravitreal ranibizumab
      (Lucentis) and to compare it with that of 1.25 mg of intravitreal bevacizumab
      (Avastin), using the same rabbit model. DESIGN: Experimental animal study.
      PARTICIPANTS: Twenty-eight Dutch-belted rabbits. METHODS: One eye of each of 20
      rabbits was injected with 0.5 mg of intravitreal ranibizumab. Both eyes of each
      of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Ranibizumab
      concentrations were measured in aqueous fluid, whole vitreous, and serum. A
      further 8 rabbits were used to measure serum and fellow ranibizumab at additional
      time points of 3 and 8 hours. MAIN OUTCOME MEASURES: Ranibizumab concentrations
      in the aqueous, vitreous, and serum. RESULTS: Although vitreous concentrations of
      ranibizumab declined in a monoexponential fashion with a half-life of 2.88 days,
      concentrations of >0.1 microg/ml ranibizumab were maintained in the vitreous
      humor for 29 days. Ranibizumab concentrations in the aqueous humor of the
      injected eye reached a peak concentration of 17.9 microg/ml, 3 days after drug
      administration. Elimination of ranibizumab from the aqueous humor paralleled that
      found in the vitreous humor, with a half-life value of 2.84 days. No ranibizumab
      was detected in the serum or the fellow eye. CONCLUSION: In the rabbit, the
      vitreous half-life of 0.5-mg intravitreal ranibizumab is 2.88 days, shorter than
      the half-life of 1.25-mg intravitreal bevacizumab of 4.32 days. No ranibizumab
      was detected in the serum or the fellow uninjected eye; whereas small amounts of
      intravitreal bevacizumab have been detected in the serum and fellow uninjected
      eye.

PMID- 18054638
TI  - Triamcinolone acetonide as adjunctive treatment to verteporfin in neovascular age
      related macular degeneration: a prospective randomized trial.
AB  - PURPOSE: To examine the use of intravitreal triamcinolone acetonide (IVTA) as
      adjunctive therapy to photodynamic therapy (PDT) in the treatment of occult and
      minimally classic choroidal neovascularization (CNV) secondary to age-related
      macular degeneration (AMD). DESIGN: Single-center prospective randomized pilot
      clinical trial. PARTICIPANTS: Thirty eyes of 30 patients with occult or minimally
      classic CNV secondary to AMD. METHODS: Patients were randomized prospectively to
      receive either PDT alone or combined PDT plus IVTA treatment for CNV secondary to
      AMD. Standard verteporfin PDT was performed in all patients. In the PDT plus IVTA
      group, a 12-mg intravitreal injection of triamcinolone acetonide was given 30
      minutes after PDT. Active lesions were retreated every 3 months for 1 year. MAIN
      OUTCOME MEASURES: Change in visual acuity and retreatment rate. RESULTS: Mean
      visual acuity remained stable in the PDT plus IVTA group (-1.9 Early Treatment
      Diabetic Retinopathy Study [ETDRS] letters; P = 0.58), but declined significantly
      in the PDT alone group (-13.3 ETDRS letters; P = 0.02). The treatment rate was
      1.13 in the PDT plus IVTA group and 3.6 in the PDT alone group (P<0.0001). Mean
      contrast sensitivity increased by 3.6 letters (P = 0.09) in the PDT plus IVTA
      group and decreased by -1.84 letters (P = 0.07) in the PDT alone group. Cataract
      progression was noted in 4 of 7 phakic eyes in the PDT plus IVTA group. Six
      patients (40%) in the combined PDT plus IVTA group required topical glaucoma
      therapy for control of elevated intraocular pressure. CONCLUSIONS: This pilot
      study demonstrated effective stabilization of visual acuity and reduced treatment
      frequency at 12 months with combination PDT plus IVTA therapy versus PDT alone.
      Larger randomized trials are ongoing to determine the efficacy and risks of PDT
      with IVTA.

PMID- 18054639
TI  - Results of penetrating keratoplasty performed with a femtosecond laser zigzag
      incision initial report.
AB  - PURPOSE: To determine the initial outcomes of utilizing a femtosecond laser to
      perform penetrating keratoplasty incisions in a zigzag pattern. DESIGN:
      Retrospective consecutive surgical series. PARTICIPANTS: Patients undergoing full
      thickness corneal transplant surgery in a referral academic practice. METHODS:
      The IntraLase femtosecond laser performed matching donor and host zigzag
      incisions in a consistent pattern in 13 eyes of 13 patients. MAIN OUTCOME
      MEASURES: Topographically determined astigmatism, imaging of incisions by
      anterior segment optical coherence tomography, and best spectacle-corrected
      visual acuity (BSCVA). RESULTS: Postoperative follow-up ranged from 3 to 9
      months. Mean astigmatism was < or =3.0 diopters (D) at all intervals beginning at
      1 month postoperatively. Maximum astigmatism was 4.25 D from month 3 onward. Nine
      eyes (69%) had < or =3 D and 6 eyes (46%) had < or =2 D by month 3. In the 8 eyes
      with full vision potential, 7 (87.5%) had BSCVA> or =20/30 by month 3; the eighth
      eye had improved to 20/25 by month 6. Optical coherence tomography images showed
      excellent anterior and posterior wound alignment, including one eye where the
      running suture loosened and was fully removed before month 3. CONCLUSIONS: The
      femtosecond laser-generated zigzag incision is biomechanically stable, resulting
      in excellent wound apposition, wound integrity with minimal suture tension, and
      recovery of good levels of BSCVA with moderate astigmatism within months of
      surgery.

PMID- 18054640
TI  - Retinal nerve fiber layer split bundles are true anatomic variants.
AB  - PURPOSE: The presence of retinal nerve fiber layer (RNFL) split bundles recently
      was described in normal eyes scanned using scanning laser polarimetry. In this
      study, the authors set out to ascertain whether RNFL split bundles can be found
      in histologic sections of normal human eyes. DESIGN: Histologic study of
      postmortem human eyes. PARTICIPANTS: Fourteen normal postmortem eyes obtained
      from 13 individuals. METHODS: Peripapillary RNFL thickness measurements were
      plotted, for each eye, from ring sections of 3.0, 3.5, 4.0, and 4.5 mm in
      diameter. The presence of superior or inferior split RNFL patterns, or both, was
      sought. MAIN OUTCOME MEASURES: The presence of superior or inferior split bundles
      or both in the histologic data. RESULTS: Five of 14 eyes demonstrated a distinct
      histologic pattern of RNFL split bundles, of which 3 were found superiorly and 2
      inferiorly. None of these 14 eyes demonstrated both a definite superior and a
      definite inferior split. CONCLUSIONS: This study provides histologic evidence
      demonstrating that RNFL split bundles are likely a true anatomic finding, rather
      than an imaging artifact, and that their presence seems to be relatively common
      in normal eyes. The presence of a split bundle, being a normal variant, should be
      distinguished from RNFL loss.

PMID- 18054641
TI  - Visual outcome and corneal changes in children with chronic
      blepharokeratoconjunctivitis.
AB  - OBJECTIVE: To describe the cause, management, and effect of chronic
      blepharokeratoconjunctivitis (BKC) on the cornea and visual function in children.
      DESIGN: Noncomparative, interventional, retrospective case series. PARTICIPANTS:
      Twenty-seven children with BKC. METHODS: Presenting age, best-corrected visual
      acuity (BCVA), refractive error, and any corneal or eyelid pathologic features
      were recorded. Treatment included modified lid hygiene, topical antibiotics, and
      steroids. Systemic therapy included oral antibiotics and, from 2003 onward,
      flaxseed oil as an alternative to long-term antibiotics. Amblyopia therapy
      included refractive correction, occlusion, or atropine therapy. MAIN OUTCOME
      MEASURES: Corneal and eyelid status, visual acuity (VA), and refractive error at
      final examination. RESULTS: Mean age at presentation was 6.9 years (range, 7
      months-15.9 years), and mean follow-up was 2.3 years (range, 5 months-6.1 years).
      All patients had discomfort, conjunctival injection, and signs of posterior
      blepharitis at presentation. Photophobia was reported in 14 patients (52%),
      whereas anterior eyelid inflammation was noted in 6 (22%). Acne rosacea was
      confirmed in 3 patients (11%). Corneal involvement occurred in 44 eyes (81%), and
      a history of recurrent chalazia was seen in 18 patients (67%). Median monocular
      BCVAs in affected eyes were 0.28 logarithm of the minimum angle of resolution
      (logMAR) units (interquartile range [IqR], 0.02-0.40) at presentation and 0.02
      logMAR units (IqR, 0.00-0.18) at last visit. Best-corrected VA improved in 70% of
      affected eyes and remained unchanged in 30%. Superimposed amblyopia was present
      and treated in 15 patients (48%). All 8 patients (20%) who failed to achieve VA
      of 0.2 logMAR units or better at the final examination had bilateral corneal
      involvement at presentation. One child experienced a systemic side effect from
      oral antibiotics. No child had significant side effects from topical treatment.
      Twelve patients (44%) received flaxseed oil as part of their tapering regimen. A
      2-year lag between symptom onset and treatment resulted, on average, in a
      reduction of 0.06 logMAR units of VA (95% confidence interval, 0.00-0.12; P =
      0.054). CONCLUSIONS: These findings suggest that visual loss may be significant
      in BKC and that delayed treatment may result in decreased final BCVA. Adequate
      management needs both topical and systemic treatment. Flaxseed oil may be an
      effective antiinflammatory nutritional therapy alternative to long-term
      antibiotics.

PMID- 18054642
TI  - Escalation of glaucoma therapy after penetrating keratoplasty.
AB  - PURPOSE: To determine the prevalence and risk factors for escalation of glaucoma
      therapy after penetrating keratoplasty (PK) and its impact on graft survival and
      visual outcome. DESIGN: Retrospective case series. PARTICIPANTS: Seven hundred
      fifteen consecutive eyes of 678 patients undergoing PK. METHODS: Retrospective
      review of every case of PK performed at King Khaled Eye Specialist Hospital
      between January 1, 2001 and December 31, 2002. MAIN OUTCOME MEASURES: Escalation
      of glaucoma therapy, graft survival, and visual outcome. RESULTS: Escalation of
      glaucoma therapy occurred in 89 (12.4%) eyes of 715 PK procedures during a mean
      follow-up of 32.2 months. Medical escalation accounted for 73 (82.0%) cases,
      whereas surgical escalation occurred in 16 (18.0%) eyes. The following were
      significantly associated with an increased risk of escalation of glaucoma
      therapy: surgical indication for PK (P<0.001), increasing patient age (P<0.001),
      preexisting glaucoma (P<0.001), recipient trephination < 7.0 mm (P = 0.02), and
      pseudophakia or aphakia (P<0.001). Eyes with escalation of glaucoma therapy had
      significant reduction in graft survival compared with eyes in which this did not
      occur (52.8% vs. 82.9%, P<0.001). Escalation of glaucoma therapy was associated
      with a significant reduction in the percentage of eyes achieving visual acuity of
      20/40 or better (9.0% vs. 42.1%, P<0.001) and a significant increase in those
      obtaining 20/200 or worse (70.8% vs. 26.7%, P<0.001). CONCLUSIONS: Escalation of
      glaucoma therapy is a serious sequela of PK that is significantly associated with
      an increased risk of graft failure and poor visual outcome.

PMID- 18054643
TI  - Optical treatment of amblyopia in astigmatic children: the sensitive period for
      successful treatment.
AB  - OBJECTIVE: To compare the effectiveness of eyeglass treatment of astigmatism
      related amblyopia in children younger than 8 years (range, 4.75-7.99 years)
      versus children 8 years of age and older (range, 8.00-13.53 years) over short (6
      week) and long (1-year) treatment intervals. DESIGN: Prospective, interventional,
      comparative case-control study. PARTICIPANTS: Four hundred forty-six
      nonastigmatic (right and left eye, <0.75 diopters [D]) and 310 astigmatic (RE, >
      or =1.00 D) Native American (Tohono O'odham) children in kindergarten or grades 1
      through 6. INTERVENTION: Eyeglass correction of refractive error, prescribed for
      full-time wear, in astigmatic children. MAIN OUTCOME MEASURES: Amount of change
      in mean right-eye best-corrected letter visual acuity for treated astigmatic
      children versus untreated, age-matched nonastigmatic children after short (6
      week) and long (1-year) treatment intervals. RESULTS: Astigmatic children had
      significantly reduced mean best-corrected visual acuity at baseline compared to
      nonastigmatic children. Astigmats showed significantly greater improvement in
      mean best-corrected visual acuity (0.08 logarithm of the minimum angle of
      resolution [logMAR] unit; approximately 1 line), than the nonastigmatic children
      (0.01 logMAR unit) over the 6-week treatment interval. No additional treatment
      effect was observed between 6 weeks and 1 year. Treatment effectiveness was not
      dependent on age group (<8 years vs. > or =8 years) and was not influenced by
      previous eyeglass treatment. Despite significant improvement, mean best-corrected
      visual acuity in astigmatic children remained significantly poorer than in
      nonastigmatic children after 1 year of eyeglass treatment, even when analyses
      were limited to results from highly compliant children. CONCLUSIONS: Sustained
      eyeglass correction results in significant improvement in best-corrected visual
      acuity in astigmatic children, including those previously believed to be beyond
      the sensitive period for successful treatment.

PMID- 18054644
TI  - Ramadan and eyedrops: the muslim perspective.
AB  - PURPOSE: To assess views of Muslims with regard to the use of eyedrops during
      fasting periods of Ramadan and to determine if demographic, religious, and
      educational factors or the perceived severity of an ocular condition influence
      these views. DESIGN: Cross-sectional survey. PARTICIPANTS: Two hundred adult
      Muslims. METHODS: A questionnaire-based survey. MAIN OUTCOME MEASURES: The main
      outcome measures studied were the proportion of respondents who believe that the
      use of eyedrops during fasting hours of Ramadan would break the fast and the
      proportion of respondents who would use drops during fasting hours of Ramadan.
      RESULTS: Of the 200 questionnaires collected, 10 were excluded because of
      incomplete data entry (n = 190). Among respondents, 63.7% (n = 121) believe that
      using eyedrops during fasting periods of Ramadan would break the fast, and only
      34.2% (n = 65) would use drops during this period. A further 34.2% (n = 65) would
      continue their regular treatment, 35.8% (n = 68) would use drops for a nonpainful
      eye condition, 66.8% (n = 127) for a painful eye condition, 35.3% (n = 67) for a
      condition that did not affect vision, and 75.8% (n = 144) would use drops during
      the fasting period for an eye condition if vision was affected. No significant
      association was noted when comparing views of respondents based on gender,
      occupation, education, and number of days the fast is observed. Statistical
      significance was reached when comparing the views of Muslims who would fast
      additional days if a fast was broken compared with those who would not (P<0.001).
      CONCLUSIONS: Ramadan could be an important cause for noncompliance with
      prescribed ophthalmic treatment. This study provides an insight into views of
      Muslims regarding use of eyedrops during Ramadan. The results suggest that
      extensive misuse of prescribed drops should be anticipated during Ramadan.

PMID- 18054646
TI  - Selection bias?

PMID- 18054647
TI  - Sleep position and eye pressure.

PMID- 18054648
TI  - Anterior segment optical coherence tomography.

PMID- 18054651
TI  - An endoscopic approach to managing dislocated IOLs.

PMID- 18054652
TI  - Black occlusive IOLs.

PMID- 18054653
TI  - Lactoferrin in Sjogren's syndrome.

PMID- 18054655
TI  - Oral drugs for viral retinitis.

PMID- 18054657
TI  - Anterior ischemic optic neuropathy.

PMID- 18054658
TI  - Orbital hemangioma.

PMID- 18054659
TI  - Choroidal coloboma.

PMID- 18054660
TI  - Fibrous histiocytoma.

PMID- 18054661
TI  - Ptosis in young soft contact lens wearers.

PMID- 18054662
TI  - Triangulation of breast lesions: review and clinical applications.
AB  - Although the concept of triangulation of breast lesions has been well-defined in
      the literature, it is still frequently misunderstood or applied incorrectly. We
      provide a review of the basic concept, discuss common misapplications of
      triangulation and the reasons they happen, and demonstrate typical and
      exceptional cases, as well as mammography-ultrasound correlations using diagrams
      and illustrative cases.

PMID- 18054663
TI  - Meniscal gymnastics: common and uncommon locations of meniscal flip and flop.
AB  - The majority of knee magnetic resonance imaging examinations are performed for
      meniscal evaluations. Displaced meniscal tears including free meniscal fragments
      are an important diagnosis as most of these tears are unstable and require
      surgical intervention. Magnetic resonance imaging can be an invaluable tool in
      the arthroscopic search for a free meniscal fragment. In addition to the commonly
      seen bucket-handle tears flipped into the intercondylar notch, it is important to
      be aware of less common locations where menisci may be displaced. First, we
      briefly summarize the basic meniscal anatomy and some of the more common tear
      patterns. We then investigate the broad range of meniscal migration.

PMID- 18054664
TI  - Traumatic injuries of the c1/c2 complex: computed tomographic imaging
      appearances.
AB  - Cervical spine fractures occur in 1 to 3% of trauma cases and account for two
      thirds of spinal cord injuries. Injury to the C1/C2 complex accounts for 19 to
      25% of cervical spine injuries. Fractures of C2 occur most frequently, 55% of
      which involve the odontoid peg. The unique anatomical relationship between the
      atlas and axis produces a variety of injury patterns not seen elsewhere in the
      spine. Numerous developmental anomalies also occur which can mimic trauma. Well
      described fracture patterns include posterior arch fractures of the atlas,
      Jefferson type fractures, fractures of the odontoid process, and Hangman's
      fractures. Traumatic subluxation of C1 on C2 and rotatory fixation also occur
      with or without associated bone injury. Computed tomography is an important tool
      for accurately assessing injuries to the C1/C2 complex, occasionally supplemented
      by dynamic computed tomography in cases of rotatory fixation. A description of
      the anatomy, common anatomical variants, and injury patterns of the atlas and
      axis illustrated by computed tomography is presented along with the relevant
      injury classifications.

PMID- 18054665
TI  - Cryoablation in the musculoskeletal system.
AB  - Pain palliation can be challenging in patients with metastases to the
      musculoskeletal system, and conventional therapy can be less than optimal for
      pain management. Recent advances in technology have allowed for the addition of
      image-guided ablation to the armamentarium for treating musculoskeletal
      metastases. This article focuses on one such technique, percutaneous
      cryoablation, and the experiences with this technique at the authors'
      institution. After a brief review of the history and theory behind cryoablation,
      the basic technique of percutaneous cryoablation of musculoskeletal metastases is
      described. This is followed by a review of the cases that have been performed at
      the authors' institution. A discussion on the many advantages and relatively few
      disadvantages of this exciting new technique is then put forth. Percutaneous
      cryoablation is beginning to emerge as a useful method of image-guided ablation
      of musculoskeletal metastases. As data continue to mount on this exciting
      application of new technology, image-guided cryoablation of musculoskeletal
      metastases appears to hold much promise in the treatment of pain related to these
      lesions.

PMID- 18054667
TI  - Two-part fractures and fracture dislocations.
AB  - Proximal humeral fractures are common and are usually osteopenic or osteoporotic
      and about 85% occur in patients older than 50. Two-part fractures account for
      approximately 28% of proximal humeral fractures, with most being surgical neck
      fractures. This article discusses the management of two-part fractures and
      analyzes the use of nonoperative treatment, conventional plating, locked plating,
      antegrade intramedullary nailing, retrograde pinning, and Kirschner wires in
      their treatment. The literature indicates that nonoperative treatment is as
      effective as conventional plating, antegrade nailing, and Kirschner wiring in
      treating two-part surgical neck fractures in older patients. The early results of
      locked plating may be better, but more studies are required to prove this. This
      article gives the results of nonoperative treatment of all types of two-part
      fractures and fracture dislocations.

PMID- 18054668
TI  - Four-part proximal humerus fractures: evaluation and treatment.
AB  - Four-part proximal humerus fractures represent a difficult entity in the
      management of upper extremity trauma. Most of these fractures are not amenable to
      operative fixation; thus, surgical address is necessarily one of fracture
      arthroplasty. Timely reestablishment of the Gothic arch using a fracture-specific
      prosthesis leads reliably to anatomic tuberosity osteosynthesis. Hence, shoulder
      arthroplasty for fracture should be considered an augmented osteosynthesis, with
      precise prosthetic implantation supplementing anatomic tuberosity reconstruction.
      Further investigations are ongoing regarding the use of specific fracture
      implants and biologic substrates in an attempt to improve further the rate of
      tuberosity healing in the older patient population after this operation.

PMID- 18054669
TI  - Reverse shoulder arthroplasty for the treatment of proximal humeral fractures.
AB  - Proximal humeral fractures occurring in elderly patients often lead to
      significant functional disability. The outcome of nonoperative management is
      disappointing. Treatment with open reduction and internal fixation may result in
      osteonecrosis of the humeral head, and pain. Hemiarthroplasty is often associated
      with tuberosity nonunion and poor function. Reverse shoulder arthroplasty is an
      attractive alternative because of the ability of the prosthesis to compensate for
      tuberosity complications. Early studies have shown promise in using the
      prosthesis to treat these difficult patients. The next step will require
      prospective, randomized studies to determine which patient groups derive any
      benefit from reverse shoulder arthroscopy. The technology should be used
      judiciously.

PMID- 18054670
TI  - Proximal humerus and humeral shaft fractures in children.
AB  - Proximal humerus fractures and fractures of the humeral shaft are relatively rare
      in children. The incidence of the former is about 1 to 3 cases/1000 population
      per year, comprising fewer than 3% of all pediatric fractures. Fractures of the
      humeral shaft represent fewer than 10% of all humerus fractures in children. Both
      types of fractures in babies and young children can be treated nonsurgically,
      because of the joint's ability to remodel. Simple swaddling with a sling or
      swaddling cloth can be the solution. For older children, splints and braces may
      be necessary for short periods of time. Fractures can sometimes be a sign of
      parental child abuse, so suspicion should remain high when evaluating children
      with these injuries.

PMID- 18054671
TI  - The operative treatment of diaphyseal humeral shaft fractures.
AB  - Fractures of the humeral shaft comprise 1% to 3% of all fractures. Incidence
      rates reveal a bimodal distribution in which there is one small peak during
      adolescence, followed by a larger spike during the fifth and sixth decades of
      life. Most humeral diaphysis fractures are simple patterns of the mid-diaphysis.
      This article emphasizes surgical approaches to humeral fractures, providing a
      review of the surgical spectrum of treatment inclusive of intramedullary nailing
      and plating, but also includes a brief discussion of the conservative approach.

PMID- 18054672
TI  - Humeral nonunion.
AB  - Humerus fractures comprise 5% to 8% of all fractures. Although uncommon,
      nonunions can present a frustrating challenge to the orthopedic surgeon. Various
      risk factors that may predispose patients to nonunion include obesity,
      osteoporosis, alcoholism, smoking, poor bone quality, and scar tissue. Many
      methods of treatment have been described with various degrees of success. The
      rates of healing of humeral nonunions by traditional means of internal fixation
      with bone graft range from 70% to 92%, although in cases of infection, poorly
      vascularized beds, and open, segmental, or severely comminuted fractures,
      secondary bony healing may still be compromised.

PMID- 18054673
TI  - Distal humerus fractures.
AB  - Fractures of the distal humerus in adults have traditionally presented a
      treatment challenge for the orthopedic surgeon. The combination of anatomic
      complexity, multifragmentary comminution, and a short distal segment, often in
      the setting of osteoporotic bone, renders these fractures difficult to treat
      successfully and often make a full restoration of function uncertain. Multiple
      methods of treatment for these fractures have been described, including bracing,
      internal fixation, hemiarthroplasty, and total elbow arthroplasty. This article
      reviews the epidemiology and classification of these injuries and the numerous
      described fixation and arthroplasty techniques. The current treatment algorithm
      and authors' preferred method of internal fixation are also illustrated.
      Additionally, the treatment of these injuries in the elderly population and the
      complications of surgical treatment are reviewed.

PMID- 18054674
TI  - Apparent capitellar fractures.
AB  - Isolated capitellar fractures are rare but are identified as such, even when they
      are more complex, because the displaced capitellar fracture is usually the most
      obvious and identifiable radiographic finding and because teaching has
      traditionally underemphasized the involvement of the trochlea in such fractures.
      The author prefers the term 'apparent capitellar fractures' and draws on his
      experience to explain why he favors three-dimensional CT for depicting fracture
      detail. This article discusses treatment options, emphasizing open reduction and
      internal fixation to restore the native elbow. Operative techniques, including
      extensile lateral exposure and olecranon osteotomy; fixation techniques; and
      elbow arthroplasty, are described. Complications, such as ulnar neuropathy and
      infection, are also covered.

PMID- 18054675
TI  - Fractures of the capitellum.
AB  - Fractures of the capitellum account for less than 1% of all elbow fractures.
      Because they may be difficult to visualize on plain radiographs, the clinician
      must have a high index of suspicion for their diagnosis. Anatomic alignment of
      these fractures is imperative; slight residual displacement may result in
      significant loss of elbow motion. Surgical management is described with open
      reduction internal fixation using variable pitch headless screws, precontoured
      plates, or bioabsorbable pins. The optimal method of fixation depends on the
      fracture pattern and degree of comminution. If the fracture fragments are too
      small for stable fixation, excision of the fragments is recommended.
      Osteonecrosis, as well as, end-stage arthrosis requiring total elbow
      arthroplasty, has been reported as a rare, but potential, complication.

PMID- 18054678
TI  - Challenges of oral medications in patients with advanced breast cancer.
AB  - OBJECTIVES: To list methods that nurses can use to monitor and ensure compliance
      with an oral agent for the treatment of metastatic breast cancer. DATA SOURCES:
      Published research articles, abstracts, and clinical experience. CONCLUSION: Oral
      chemotherapeutic agents offer the advantages of patient control and less
      interference with administration and, frequently, improved tolerability profiles
      versus conventional infusion chemotherapy. However, there is the difficulty of
      ensuring optimal adherence to the treatment plan. Adherence rates for oral
      chemotherapy vary widely in studies, and can depend on psychological and
      socioeconomic factors as well as individual patient outcome expectations.
      IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can identify factors
      influencing adherence to therapy and assess those patients appropriate for oral
      therapy. Oncology nurses can facilitate follow-up visits, ask appropriate
      adherence questions, and successfully manage the shift of administration
      responsibility to the patient.

PMID- 18054677
TI  - Overcoming treatment challenges in advanced breast cancer.
AB  - OBJECTIVES: To describe new clinical findings, efficacy, and safety regarding the
      use of targeted agents in the treatment of HER2-positive metastatic breast
      cancer. DATA SOURCES: Published research articles, abstracts, and clinical
      experience. CONCLUSION: HER2-positive cases of breast cancer tend to be more
      aggressive and more likely to become resistant to therapy than HER2-negative
      tumors. The current standard approach to patients with HER2-positive metastatic
      breast cancer includes the use of trastuzumab. Because cellular mechanisms can
      arise that can block the efficacy of this approach (and result in clinical
      resistance), recent research has led to the development of lapatinib, a targeted
      therapy that can act on HER2 inside the cell to disrupt the signaling pathways
      thought to be part of tumorigenic mechanisms. IMPLICATIONS FOR NURSING PRACTICE:
      Oncology nurses should be aware of the treatment strategies for HER2-positive
      metastatic breast cancer and its limitations, which is essential for providing
      optimal nursing care.

PMID- 18054679
TI  - Managing treatment side effects in advanced breast cancer.
AB  - OBJECTIVES: To compare and contrast the side-effect profiles of antineoplastic
      therapy options used in the treatment of metastatic breast cancer. DATA SOURCES:
      Published research articles, abstracts, and clinical experience. CONCLUSION:
      Novel and existing antineoplastic agents used in the treatment of metastatic
      breast cancer generally have mild side effects, but can have the potential for
      serious reactions. Nausea/vomiting, diarrhea, stomatitis/mucositis, and
      dermatologic and cardiovascular effects are common. Strategies such as dietary
      changes, over-the-counter remedies, and dose modification can be used to
      counteract these mild effects. IMPLICATIONS FOR NURSING PRACTICE: The oncology
      nurse should be aware of common adverse events associated with antineoplastic
      agents, recognize early side-effect signs, and be ready with effective strategies
      to mitigate side effects when and if they occur.

PMID- 18054680
TI  - Choosing the appropriate breast cancer therapy for today's breast cancer patient.
AB  - OBJECTIVES: To identify which patients might be the best candidates to receive
      combination targeted therapies for the treatment of metastatic breast cancer.
      DATA SOURCES: Published research articles, abstracts, and clinical experience.
      CONCLUSION: Factors including tumor size, age, HER2 positivity, and hormone
      receptor content help determine the optimal approach toward the treatment of
      breast cancer in the individual patient. Further research will clarify the role
      of targeted agents in the adjuvant setting, along with the hope of a cure.
      IMPLICATIONS FOR NURSING PRACTICE: The oncology nurse must be aware of current
      and emerging therapies - whether they be intravenously or orally administered -
      and the proper methods to help characterize patients who might likely benefit
      from these agents.

PMID- 18054685
TI  - Cerebrospinal fluid analysis in the diagnosis and treatment of arterial ischemic
      stroke.
AB  - With the advent of magnetic resonance imaging as a rapid and accurate way to
      diagnose arterial ischemic stroke, cerebrospinal fluid assessment is rarely
      performed, unless infectious or inflammatory processes are obvious. Recent
      advances in the understanding of the pathophysiology of childhood stroke have
      implicated a growing list of discrete or occult infectious and inflammatory
      conditions which may involve intracranial arteries and neighboring structures.
      Cerebrospinal-fluid assessment may allow the detection of markers identifying
      processes (including infectious, inflammatory, metabolic, and traumatic)
      potentially involved in cerebral vasculopathy and stroke. The analysis of
      cerebrospinal fluid in arterial ischemic strokes, including apparently idiopathic
      strokes, may yield essential information on pathophysiology, allowing for optimal
      therapeutic decisions and prognostic considerations.

PMID- 18054687
TI  - Square wave jerks in children and adolescents.
AB  - Square wave jerks are involuntary, horizontal, saccadic intrusions that interrupt
      fixation. Each square wave jerk consists of an initial saccade that moves the
      fovea away from the intended position of fixation, followed by a second saccade
      in the opposite direction, which refoveates the fixation position. Square wave
      jerks reportedly occur in 24-60% of healthy adults. No previous study of square
      wave jerks in children and adolescents is available. We recorded eye movements
      using an infrared eye tracker in 38 participants aged 8-19 years while they
      fixated on a visual target for 1 minute. The frequency of square wave jerks, and
      the durations, amplitudes, and peak velocities of their saccades, were calculated
      and correlated with age. Ninety percent of participants had square wave jerks.
      Their median frequency was 3 per minute (range, 1-18), median duration was 249
      milliseconds, the median amplitude of their saccades was 0.81 degrees, and the
      median peak velocity was 60 degrees/second. No parameter of square wave jerks
      correlated with age. The prevalence of square wave jerks is high in children and
      adolescents. This finding may be a feature of the less mature brain, and may
      reflect an inability to suppress unwanted supranuclear triggers for saccades.

PMID- 18054686
TI  - White-matter injury is associated with impaired gaze in premature infants.
AB  - Periventricular leukomalacia is a risk factor for visual impairment in children
      born prematurely. The impact of diffuse white-matter injury, as detected on
      magnetic resonance imaging, on early visual function is unknown. We developed two
      5-point visual-gaze scores to analyze the association between this clinical
      assessment and white-matter injury in 93 premature neonates <34 weeks of
      gestational age at birth. Older postmenstrual age was associated with higher
      values of the two gaze scores. Infants with moderate or severe white-matter
      injury had lower scores than their peers without white-matter injury (0.41
      points, 95% confidence interval of 0.13-0.69 for visual fixation score; and 0.70
      points, 95% confidence interval of 0.30-1.10 for conjugate score, P < 0.005).
      Using the results from both scales, a score of >or=9 in an infant examined at
      >or=36 weeks postmenstrual age predicted normal white matter on magnetic
      resonance examination, with a sensitivity of 84% and a specificity of 100%. These
      preliminary findings suggest that white-matter injury affects visual function
      even before term equivalent postmenstrual age.

PMID- 18054688
TI  - Effects of iron supplementation on attention deficit hyperactivity disorder in
      children.
AB  - Iron deficiency has been suggested as a possible contributing cause of attention
      deficit hyperactivity disorder (ADHD) in children. This present study examined
      the effects of iron supplementation on ADHD in children. Twenty-three nonanemic
      children (aged 5-8 years) with serum ferritin levels <30 ng/mL who met DSM-IV
      criteria for ADHD were randomized (3:1 ratio) to either oral iron (ferrous
      sulfate, 80 mg/day, n = 18) or placebo (n = 5) for 12 weeks. There was a
      progressive significant decrease in the ADHD Rating Scale after 12 weeks on iron
      (-11.0 +/- 13.9; P < 0.008), but not on placebo (3.0 +/- 5.7; P = 0.308).
      Improvement on Conners' Parent Rating Scale (P = 0.055) and Conners' Teacher
      Rating Scale (P = 0.076) with iron supplementation therapy failed to reach
      significance. The mean Clinical Global Impression-Severity significantly
      decreased at 12 weeks (P < 0.01) with iron, without change in the placebo group.
      Iron supplementation (80 mg/day) appeared to improve ADHD symptoms in children
      with low serum ferritin levels suggesting a need for future investigations with
      larger controlled trials. Iron therapy was well tolerated and effectiveness is
      comparable to stimulants.

PMID- 18054689
TI  - Diffusion tensor imaging of brain plasticity after occipital lobectomy.
AB  - Reorganization involving residual visual pathways with unilateral damage to the
      primary visual cortex was previously described. Using diffusion tensor imaging,
      we measured water diffusion-related changes in the optic radiation contralateral
      to occipital lobe ablation in children with intractable epilepsy. We studied 10
      children who had undergone a resection of the unilateral occipital cortex and 13
      control subjects. Diffusion tensor imaging was acquired using a 1.5 Tesla
      magnetic resonance scanner. Fiber bundles representing optic radiation were
      tracked. Diffusion parameters included mean fractional anisotropy, apparent
      diffusion coefficient, and diffusion parallel and perpendicular to the fiber
      tract. In the surgical group, fractional anisotropy values of optic radiation
      contralateral to the side of resection exhibited a significant positive partial
      correlation (r = 0.752, P = 0.019) with duration of time between surgery and
      diffusion tensor imaging acquisition, after controlling for age. The apparent
      diffusion coefficient and parallel diffusivity were higher in the surgical versus
      the control group, but did not differ among patients. After unilateral resection
      of the occipital lobe, the contralateral optic radiation undergoes significant
      changes in anisotropy. Such structural white-matter changes may represent an
      adaptive response because of unilateral occipital ablation, and may account for
      plasticity changes observed in functional magnetic resonance imaging.

PMID- 18054690
TI  - Time interval from a brain insult to the onset of infantile spasms.
AB  - The temporal latency between an encephalopathic event and the onset of infantile
      spasms cannot be determined in the majority of symptomatic cases (e.g. genetic
      conditions, cerebral malformations). However, we can measure this interval when a
      previously normal infant sustains brain injury followed by infantile spasms. This
      information has implications for understanding the underlying pathophysiologic
      basis for infantile spasms and, also, is germane to allegations that a close
      temporal relationship between vaccination and the onset of this seizure disorder
      establishes causation. We identified 19 published cases with sufficient
      information. The interval between brain injury and the onset of infantile spasms
      ranged from 6 weeks to 11 months (mean = 5.1 months). A similar temporal latency
      occurs in children with perinatal cerebral infarction and infantile spasms. We
      conclude that infantile spasms do not occur acutely following an encephalopathic
      event. This interval of weeks to months is consistent with prior studies
      indicating temporal latency between brain injury and the onset of other types of
      epilepsy, as well as with the previously proposed developmental desynchronization
      hypothesis. The findings refute claims that a close temporal association between
      an immunization and the onset of infantile spasms establishes causation.

PMID- 18054691
TI  - Influence of the ketogenic diet on 24-hour electroencephalogram in children with
      epilepsy.
AB  - The ketogenic diet is a therapeutic diet used to treat medically refractory
      epilepsy in children. It was found to be effective and safe. Apart from a reduced
      number of seizures, positive cognitive effects were described. The mechanisms of
      action are not fully understood, but both antiseizure and antiepileptogenic
      effects were proposed. Among other changes ascribed to the introduction of the
      diet, changes in electroencephalogram patterns might contribute to an
      understanding of the effects of the ketogenic diet. In this study, 23 children
      (mean age, 6.5 years) with pharmacoresistant epilepsy were started on the diet.
      They were examined via 24-hour ambulatory electroencephalogram directly before
      starting the diet, and after 3 months of treatment. The changing
      electroencephalogram pattern was evaluated qualitatively and semiquantitatively.
      Background activity, interictal epileptiform activity, ictal activity, and
      seizure reduction were evaluated. Quality of life was estimated on a visual
      analog scale. In 15 of 23 patients, the electroencephalogram indicated
      improvement in terms of more normal background activity or decreased interictal
      epileptiform activity. This improvement was seen in both seizure-reduction
      responders and nonresponders, and was not predictive of response to treatment.

PMID- 18054692
TI  - Acute Q fever in children presenting with encephalitis.
AB  - We describe the cases of three children with encephalitis associated with
      Coxiella burnetii infection. Neurologic features ranged from status epilepticus
      and coma to headache and pseudotumor cerebri syndrome. Patients had good response
      to antibiotic treatment with doxycycline and recovered fully. Q fever should be
      included in the differential diagnosis of children with encephalitis, and routine
      serological testing should be considered, especially in endemic areas.

PMID- 18054693
TI  - Split notochord syndrome with congenital unilateral Horner's sign.
AB  - A 2-year-old boy exhibited congenital right Horner's sign and right finger,
      wrist, and elbow flexion arthrogryposis. He had dyspnea and feeding difficulty 12
      hours after birth. Radiologic examination revealed a thoracoabdominal intestinal
      tube and mediastinal cystic lesion at the right side, with vertebral anomaly at
      the cervical level. Histopathologically, the intestinal tube was diagnosed as
      bowel duplication. Because the mediastinal lesion could not be resected
      surgically, no histopathological diagnosis was made. Embryologically, the
      combination of transdiaphragmatic duplication, mediastinal cystic lesion,
      anterior spina bifida, and hemivertebra suggested notochord malformation. The
      diagnosis was split notochord syndrome, an extremely rare embryological
      malformation syndrome. Congenital unilateral Horner syndrome often has unknown
      etiology. In this case, cervical vertebral anomalies and mediastinal cystic
      lesion implied a compressed nerve root, resulting in Horner syndrome and right
      finger, wrist, and elbow flexion joint contracture. Split notochord syndrome
      should be included in differential diagnosis of congenital unilateral Horner
      syndrome.

PMID- 18054694
TI  - Novel deletion mutation in GFAP gene in an infantile form of Alexander disease.
AB  - Alexander disease is a rare, fatal neurologic disorder characterized by white
      matter degeneration and cytoplasmic inclusions in astrocytes known as Rosenthal
      fibers, which are immunohistochemically positive to glial fibrillary acidic
      protein. Mutations in the glial fibrillary acidic protein gene were reported in
      patients with Alexander disease who had clinical and pathologic characteristics
      of the disease. All reported cases manifest heterozygous missense mutations,
      except for some insertions or deletions with no frame shift. Our patient had a
      heterozygous deletion of genomic sequence 1247-1249GGG>GG in exon 8 of the glial
      fibrillary acidic protein gene, which leads to a frame shift changing 16 amino
      acids and inducing a stop codon at codon 431 of 432 codons. The deletion mutation
      induces a structural conformation change in glial fibrillary acidic protein and
      their abnormal aggregation in astrocytes. This is the first report of a novel
      deletion mutation in the glial fibrillary acidic protein gene with a frame shift
      associated with Alexander disease.

PMID- 18054695
TI  - Hemolytic anemia presenting with idiopathic intracranial hypertension.
AB  - We report on an 8-year-old girl with hemolytic anemia because of infection with
      parvovirus B19 and increased intracranial pressure. She presented acutely with
      headache, vomiting, and mild scleral and mucosal icterus. Upon evaluation, the
      patient exhibited profound hemolytic anemia, papilledema, and increased
      intracranial pressure. The patient was treated with intravenous immunoglobulin,
      prednisone, and packed red blood cells. Concurrent with an improvement of her
      anemia, she experienced a gradual resolution of her headache, vomiting, and optic
      disc swelling. Signs of idiopathic intracranial hypertension may occur as a
      consequence of severe anemia, and are reversible upon correction of the
      underlying hematologic disorder.

PMID- 18054696
TI  - Infantile botulism caused by Clostridium butyricum type E toxin.
AB  - The case of a 9-month-old boy with infantile botulism caused by Clostridium
      butyricum type E toxin is reported. Because infantile botulism is rare in Japan,
      it was difficult to diagnose it at an early stage. Electrophysiologic findings
      were useful for the diagnosis, and were characterized by incremental responses
      (waxing) to short intervals and rapid repetitive nerve stimulation. A bioassay
      for botulism in mice indicated that the patient had botulism due to type E or F
      botulinum toxin. C. butyricum type E was isolated from his feces, confirming the
      diagnosis. This is the first known case of infantile botulism due to C. butyricum
      type E toxin in Japan.

PMID- 18054697
TI  - Primary Ewing sarcoma of lumbar spine with massive intraspinal extension.
AB  - Primary vertebral Ewing sarcoma-primitive neuroectodermal tumor is uncommon.
      Although epidural extension has been seen in such tumors, cases with massive
      intraspinal involvement are decidedly rare. Here we present the case of a 4-year
      old girl with back pain and difficulty walking. Magnetic resonance imaging showed
      a mass filling the spinal canal from T(11) to the L(3)/L(4) levels. Vertebral
      involvement with extension into the paraspinal soft tissue through neural
      foramina was seen. Histologically, a small-blue-cell tumor with strong membranous
      CD99 reactivity was noted. Molecular analysis revealed translocation
      t(11;22)(q24;q12), thus confirming the diagnosis of Ewing sarcoma-primitive
      neuroectodermal tumor. Our case emphasizes that vertebral Ewing sarcoma-primitive
      neuroectodermal tumor may present with massive intraspinal extension and should
      be included in the differential diagnosis of intraspinal lesions.

PMID- 18054698
TI  - Acquired neuromyotonia in childhood: case report and review.
AB  - Recently characterized as an immune-mediated channelopaty, Isaacs' syndrome (also
      known as acquired neuromyotonia) was first described in 1961 in two men with
      persistent, generalized muscle stiffness, in addition to spontaneous, rapid
      discharges of motor-unit potentials on electromyography. In the peripheral
      nervous system, antibodies targeted to voltage-gated potassium channels induce
      hyperexcitability of motor axons, resulting in signs of muscle stiffness or of
      pseudomyotonia. A spontaneous burst of single motor-unit activity, and myokymic
      and neuromyotonic discharges, are the most characteristic features found in
      electromyography studies. This report describes Isaacs' syndrome in a child, in
      whom the diagnosis was made by clinical features of acquired, spontaneous muscle
      overactivity and typical electromyographic findings.

PMID- 18054699
TI  - Muscle pain as the only presenting symptom in a girl with dystrophinopathy.
AB  - We present a family with dystrophinopathy in whom the proband is a female aged
      4.5 years, who presented with exertional muscle pain without weakness. Familial
      analysis identified a maternal nephew of the proband who demonstrated a similar
      clinical picture, with asymptomatic cardiomyopathy. A DNA analysis revealed an in
      frame deletion in the proximal part of domain II of the dystrophin gene.
      Extensive familial analysis indicated that the asymptomatic maternal grandfather
      transmitted the deletion. This is the first report of a young female patient with
      exertional muscle pain as the only early presenting symptom of dystrophinopathy.

PMID- 18054700
TI  - Case of pediatric acquired chronic hepatocerebral degeneration.
AB  - Acquired chronic hepatocerebral degeneration is a central nervous system disorder
      secondary to several conditions related to hepatic dysfunction. Clinical features
      of acquired chronic hepatocerebral degeneration include a hyperkinetic
      extrapyramidal syndrome, neuropsychiatric symptoms, or both. We present for the
      first time a pediatric case of acquired chronic hepatocerebral degeneration
      secondary to endstage biliary disease. The pediatric phenotype of acquired
      chronic hepatocerebral degeneration is presented, and the differential diagnosis
      in regard to Wilson's disease and management alternatives are discussed.

PMID- 18054703
TI  - Saphenous vein graft aneurysm masquerading as a left atrial mass: diagnosis by
      contrast transesophageal echocardiography.
AB  - We describe the first reported case of a saphenous vein graft aneurysm mimicking
      a left atrial (LA) mass on echocardiographic imaging in a 62-year-old man 22
      years after coronary bypass surgery. On presentation with worsening angina, a
      transthoracic echocardiogram revealed a LA mass. Coronary angiography showed
      severe native coronary artery and graft disease. The saphenous vein graft to the
      first obtuse marginal branch of the left circumflex coronary artery appeared
      ectatic and aneurysmal and was diffusely diseased. Transesophageal
      echocardiography demonstrated a well-circumscribed mass apparently within the LA,
      with an area of central echolucency and a surrounding crescentic region of
      increased echodensity, with absent flow by color and spectral Doppler techniques.
      After an intravenous bolus injection of Definity, the area of central echolucency
      within the mass was opacified compatible with a vascular origin. Pulsatile
      contrast flow was seen predominantly in diastole consistent with a coronary
      arterial flow pattern. Thus, contrast transesophageal echocardiography confirmed
      the diagnosis of a saphenous vein graft aneurysm invaginating the lateral aspect
      of the LA, mimicking a true LA mass, highlighting a novel use for this
      technology.

PMID- 18054704
TI  - Takotsubo cardiomyopathy: An under-recognized myocardial syndrome.
AB  - Takotsubo cardiomyopathy is characterized by reversible left ventricular
      dysfunction with apical ballooning and is triggered by marked psychological or
      physiological stress in the absence of significant epicardial coronary artery
      disease. Clinically, this unique myocardial syndrome mimics acute myocardial
      infarction, and it has been considered to be a rare entity with a good prognosis.
      The literature on takotsubo cardiomyopathy is limited by selection bias and
      patient heterogeneity, but recent data suggest the syndrome is more prevalent,
      e.g., in critically ill, non-cardiac patients. Prompt diagnosis and aggressive
      therapy are essential for a rapid recovery. Clinicians should increase their
      awareness of this syndrome and more research should be carried out on the
      epidemiology, pathophysiology, and treatment of takotsubo cardiomyopathy.

PMID- 18054705
TI  - Synthesising the 12-lead electrocardiogram: Trends and challenges.
AB  - An area of electrocardiography which has received much interest of late is that
      of synthesising the 12-lead ECG from a reduced number of leads. The main
      advantage of this approach is obvious, as fewer recording sites are required to
      capture the same information. This, in turn, streamlines the ECG acquisition
      process with little detriment to the integrity of information used for
      interpretation. In the current article, we provide an overview of ECG synthesis
      along with a description of various 'limited lead' systems that have been
      reported in the literature. Based on this, several suggestions as to what the ECG
      of the future may entail have been made.

PMID- 18054706
TI  - Determination of hepatitis B virus DNA incidence, viral load, and mutations in
      blood donors with HBsAg and anti-HBs-negative serology and antibodies to
      hepatitis B core antigen.
AB  - BACKGROUND: The aim of the present study was to determine hepatitis B virus DNA
      incidence, viral load, and mutations in blood donors with HBsAG and anti-HBs
      negative serology and antibodies to hepatitis B core antigen. METHODS: Blood
      samples were collected from 1000 blood donors with HBsAg-negative test results.
      Anti-HBc total screening was performed using the ELISA method. HBsAg
      negative/anti-HBc total-positive samples were tested for anti-HBs, anti-HBc IgM,
      HBeAg, and anti-HBe. Samples with isolated anti-HBc were determined for viral
      load of HBV DNA using real-time PCR. RESULTS: Anti-HBc total was established as
      positive in 200 (20%) of the 1000 blood donors. While anti-HBs was negative in 59
      (29.5%) of the 200 anti-HBc-positive samples, it was found to be positive in 141
      (70.5%) of them. All of the other hepatitis B markers were negative in all of the
      anti-HBs-negative samples. HBV DNA was not detected in the sera of the isolated
      anti-HBc-positive blood donors with real-time PCR. CONCLUSION: Although we could
      not detect HBV DNA in the sera of the isolated anti-HBc-positive blood donors,
      findings in the literature suggest that anti-HBc testing should be used in
      combination with HBsAg for the screening of blood donors to reduce risk. After
      that, the most appropriate algorithm to follow can be HBV DNA screening of
      donors.

PMID- 18054707
TI  - Trends in heart failure mortality in England and Wales since 1950.
AB  - BACKGROUND: This study aims to analyse trends in heart failure mortality for
      England and Wales from 1950 to 2003. METHODS: A retrospective observational study
      was conducted using death certificate and population data from the Office for
      National Statistics. RESULTS: Unadjusted heart failure deaths rose by a factor of
      more than four between 1950 and 1974 and then fell by a quarter by 2003. When
      standardised for changes in the age, sex and size of the population, there was a
      tripling in mortality rate from 1950 to the mid-1970s and since then, a sustained
      decline in mortality rate of 50% by 2003. The unadjusted female heart failure
      death rate has been between 1.5-2 times that of males since the early 1970s, but
      this is much less marked when the differences in the age distribution and sizes
      of the male and female populations are taken into account. Heart failure
      mortality trends are similar to those of coronary heart disease (CHD), but the
      peak is about 10 years earlier, and the male/female ratios are reversed. There is
      a continuing rise in deaths from both heart failure and CHD in the very elderly
      (>85 years). CONCLUSION: Unlike hospital trends, deaths from heart failure in the
      community in England and Wales show a decline since the early 1970s, in spite of
      an ageing population. This may reflect genuine changes in heart failure
      incidence, or parallel changes in CHD.

PMID- 18054708
TI  - Blood oxygen level-dependent (BOLD) MRI: A novel technique for the assessment of
      myocardial ischemia as identified by nuclear imaging SPECT.
AB  - BACKGROUND: The different levels of deoxyhemoglobin in the ischemic myocardium,
      induced by stressors such as dipyridamole, can be detected by blood oxygen level
      dependent (BOLD) MRI and may be used to diagnose myocardial ischemia. The aim of
      this study was to assess the signal change in the myocardium on BOLD MRI as well
      as wall thickening between rest and dipyridamole stress images in ischemic and
      non-ischemic myocardium as identified on SPECT imaging. METHODS: Twelve patients
      with stress-induced myocardial ischemia on SPECT underwent rest and dipyridamole
      stress MRI using a double breath-hold, T2()-weighted, ECG-gated sequence to
      produce BOLD contrast images as well as cine-MRI for wall thickening assessment
      in 10 of the 12 patients. Signal change on BOLD MRI and wall thickening were
      compared between rest and stress images in ischemic and non-ischemic myocardial
      segments as identified on SPECT. In each patient, two MRI slices containing 16
      segments per slice were analysed. RESULTS: In total, there were 384 segments for
      BOLD analysis and 320 for wall thickening. For BOLD signal 137 segments
      correlated to segments with reversible ischemia on SPECT and 247 to normal
      segments, while for wall thickening 112 segments correlated to segments with
      reversible ischemia and 208 to normal segments. The average BOLD MRI signal
      intensity change was -13.8 (+/-16.3)% in the ischemic segments compared to -10.3
      (+/-14.7)% in the non-ischemic segments (p=0.05). The average wall thickening was
      6.4 (+/-3.4) mm in the ischemic segments compared to 8.7 (+/-3.8) mm in the non
      ischemic segments (p<0.0001). CONCLUSION: Stress-induced ischemic myocardium has
      a different signal change and wall thickening than non-ischemic myocardium and
      may be differentiated on BOLD MRI. Larger studies are needed to define a
      threshold for detection and to determine the sensitivity and specificity of this
      technique.

PMID- 18054709
TI  - Influence of the Trp64Arg polymorphism in the beta 3 adrenoreceptor gene on
      insulin resistance, adipocytokine response, and weight loss secondary to
      lifestyle modification in obese patients.
AB  - BACKGROUND: The aim of our study was to investigate the influence of the Trp64Arg
      polymorphism in the beta 3 adrenoreceptor gene on adipocytokine response, insulin
      resistance, and weight loss secondary to lifestyle modification (Mediterranean
      hypocaloric diet and exercise) in obese patients. METHODS: A population of 65
      obese (BMI >30) non-diabetic outpatients was analyzed in a prospective way.
      Before and after 3 months of a lifestyle modification program, indirect
      calorimetry, bioimpedance, blood pressure, serial assessment of nutritional
      intake for 3 days via written food records, and biochemical analysis were
      performed. The lifestyle modification program consisted of a hypocaloric diet
      (1520 kcal, 52% carbohydrates, 25% lipids, and 23% proteins). The exercise
      program consisted of an aerobic exercise at least three times a week (60 min
      each). The statistical analysis was performed for Trp64/Arg64 and Arg64/Arg64
      combined as a mutant group and for type Trp64/Trp64 as a wild group. RESULTS: The
      mean age of the study participants was 45.8+/-16.8 years and the mean BMI was
      34.4+/-4.6 kg. There were 18 males (27.7%) and 47 females (72.3%). Fifty-five
      patients (84.6%; 15 males/40 females) had the Trp64/Trp64 genotype (wild group)
      and ten patients (15.4%; 3 males/7 females) had Trp64/Arg64 (mutant group). In
      the wild group, BMI, weight, fat mass, systolic blood pressure and waist
      circumference decreased. In this group, resting metabolic rate (RMR), RMR
      corrected by fat free mass, and VO(2) increased. In the mutant group, BMI,
      weight, fat mass, and waist circumference decreased. A significant increase was
      detected in RMR and VO(2) as well. No differences were detected between baseline
      values in the two groups. CRP levels were higher in the mutant group than in the
      wild variants. No differences were detected in other parameters. Only leptin
      levels decreased significantly in both the wild group (10.1%; p<0.05) and the
      mutant group (13.6; p<0.05). CONCLUSION: This study showed that the beneficial
      effect of mild weight reduction by a low caloric diet and exercise program is the
      greatest in subjects with a normal homozygote beta 3 adrenoreceptor gene.

PMID- 18054710
TI  - Erectile dysfunction as the presenting symptom of a pheochromocytoma.
AB  - We report the case of a 59-year-old man with a pheochromocytoma in which erectile
      dysfunction was the main symptom. Erectile function was related to the amount of
      noradrenaline secreted by the tumor, as was determined when recurrence of the
      malignancy was diagnosed twice. Erectile function could be restored by lowering
      the level of noradrenaline excretion, either by removal of the noradrenaline
      producing tumor or by treatment with doxazosin. By stimulating alpha-1
      adrenoceptors, high levels of noradrenaline are likely to result in excessive
      contraction of the corpus cavernosum and penile vessels and, thereby, cause
      erectile dysfunction.

PMID- 18054711
TI  - Bedside ultrasound diagnosis of aortic dissection in a cocaine abuser.
AB  - Aortic dissection and myocardial infarction are two well-known and well-reported
      complications of cocaine abuse. This case report describes a patient with cocaine
      induced myocardial infarction who was also found to have a type A aortic
      dissection. Interestingly, this potentially fatal complication was detected by a
      bedside 2D echocardiogram.

PMID- 18054712
TI  - Heart failure: An unusual cause.
AB  - Renal artery aneurysms are uncommon and are usually detected when renal
      angiography is performed for other indications. Less often, they may present with
      loin pain, hematuria, renovascular hypertension, and a palpable mass. Renal
      artery aneurysms larger than 1.0 cm presenting with resistant hypertension and
      all aneurysms larger than 2.0 cm are the usual indications for surgical
      intervention. The most important indications for surgical repair appear to be the
      presence of concurrent hypertension and female gender (because of the higher
      chances of catastrophic rupture of the aneurysm during pregnancy). Surgery may
      result in better control of hypertension in some cases. In this report, we
      highlight a rare case of a huge aneurysm of the left renal artery presenting with
      resistant renovascular hypertension and heart failure. Aneurysmectomy, followed
      by repair of the renal artery, resulted in good control of heart failure and
      hypertension.

PMID- 18054713
TI  - McCune-Albright syndrome associated with acromegaly and bipolar affective
      disorder.
AB  - McCune-Albright syndrome is a rare disorder caused by an activating mutation in
      the gene (GNAS1) encoding the subunit of the G protein. This syndrome is
      characterized by polyostotic fibrous dysplasia, cafe-au-lait pigmentation, and
      multiple endocrine hyperfunction. A 29-year-old male with polyostotic fibrous
      dysplasia, cafe-au-lait pigmentations, and pituitary adenoma is presented in this
      report. The patient had accompanying bipolar affective disorder, which might have
      been caused by the underlying genetic abnormality.

PMID- 18054714
TI  - Pseudo atrial flutter.
AB  - Atrial flutter typically has a cycle length of 200 ms (300 cycles/min or 5 Hz);
      with 4:1 conduction through the AV node, this would lead to a ventricular rate of
      75 bpm. We present a case of a patient with a Parkinsonian tremor at a frequency
      of 300 cycles/min that masqueraded as atrial flutter on the limb leads of a 12
      lead ECG. He had presented with a respiratory tract infection and his bedside
      rhythm monitor appeared to show atrial flutter. This appeared consistent on a
      printed (lead II) rhythm strip. His intrinsic sinus rate was coincidentally 75
      bpm, which added to the confusion in the initial assessment of his rhythm
      (mistaken to be atrial flutter with 4:1 AV conduction). Advice was sought
      regarding management of his atrial 'arrhythmia' and the appropriateness of
      anticoagulation and cardioversion. A 12-lead ECG was performed and assessment of
      this revealed normal sinus rhythm. He therefore avoided unnecessary therapy.

PMID- 18054715
TI  - Austrian's syndrome: The first described case of pneumococcal meningitis
      pneumonia and endocarditis in an injecting drug user.
AB  - We describe the first reported case of Austrian's syndrome in an injecting drug
      user (IDU). The triad of endocarditis, meningitis and pneumonia caused by
      invasive pneumococcal disease (IPD) is most commonly associated with excess
      alcohol. Injecting drug use is a recognised risk factor for IPD, whose prevalence
      and resistance continue to rise. We propose that injecting drug use is associated
      with Austrian's syndrome and that it should at least be considered in 'at risk'
      groups presenting with IPD. Furthermore, IDU presenting with IPD, meningitis and
      pneumonia should be considered for echocardiography.

PMID- 18054716
TI  - Exceptional association of diffuse anaplastic myeloma with microangiopathic
      anemia.

PMID- 18054717
TI  - Primary hyperparathyroidism presenting as redness of eyes.

PMID- 18054718
TI  - Markedly elevated BNP levels unrelated to heart failure in a young septic patient
      postcesarean section.

PMID- 18054720
TI  - Internal medicine admissions.

PMID- 18054719
TI  - Hepatic veno-occlusive disease associated with the use of Gynura segetum.

PMID- 18054721
TI  - Trends in admissions to internal medicine wards in a peripheral hospital in
      Israel.

PMID- 18054722
TI  - Acute respiratory distress syndrome (ARDS) secondary to talc pleurodesis.

PMID- 18054723
TI  - The h-index: a new way of assessing the scientific impact of individual CAM
      authors.

PMID- 18054724
TI  - The management of cancer-related fatigue after chemotherapy with acupuncture and
      acupressure: a randomised controlled trial.
AB  - BACKGROUND: Cancer-related fatigue after chemotherapy is a difficult symptom to
      manage in practice and the most disruptive symptom in patients' lives.
      Acupuncture is a popular complementary therapy among cancer patients and some
      evidence exists that it could potentially alleviate fatigue by stimulating
      'energy' points in the body. Hence, this study was carried out to assess the
      effects of acupuncture and acupressure in managing cancer-related fatigue and the
      feasibility of running a randomised trial with these two complementary therapies
      in preparation for a large trial. METHODS: This study was a randomised controlled
      trial. Forty-seven patients with cancer who experienced moderate to severe
      fatigue were randomised either to an acupuncture group (n=15), an acupressure
      group (n=16) or a sham acupressure group (n=16). The acupuncture group received
      six 20-min sessions over 2 weeks, while the patients in the two acupressure
      groups were taught to massage/press the points and did so daily thereafter for 2
      weeks on their own. Patients completed the Multidimensional Fatigue Inventory
      before randomisation, at the end of the 2-week intervention and again about 2
      weeks after the end of the intervention. RESULTS: Significant improvements were
      found with regards to General fatigue (P<0.001), Physical fatigue (P=0.016),
      Activity (p=0.004) and Motivation (P=0.024). At the end of the intervention,
      there was a 36% improvement in fatigue levels in the acupuncture group, while the
      acupressure group improved by 19% and the sham acupressure by 0.6%. Improvements
      were observed even 2 weeks after treatments, although they were lower (22%, 15%,
      7%, respectively). Acupuncture was a more effective method than acupressure or
      sham acupressure. Subjects needed a longer treatment period to have more
      sustained results. The trial was methodologically feasible. CONCLUSION:
      Acupuncture shows great potential in the management of cancer-related fatigue. As
      a randomised trial with acupuncture is feasible and preliminary data shows
      significant improvements, it should be tested further using a large sample and a
      multicentre design.

PMID- 18054725
TI  - Acupuncture for chronic pain within the research program of 10 German Health
      Insurance Funds--basic results from an observational study.
AB  - OBJECTIVES: To investigate which patients receive acupuncture in the framework of
      statutory health insurance in Germany, how treatment was carried out, and what
      results were achieved. DESIGN: Basic documentation (carried out by physician)
      within a prospective observational study. SETTING: 454,920 patients with at least
      one of the three chronic pain conditions including headache, low back pain and
      osteoarthritis treated by 8727 medical acupuncturists (panel doctors) within the
      scope of a reimbursement program. RESULTS: Fifty-three percent of the patients
      were treated by general practitioners, 19% by orthopaedists and 9% by internists.
      Eighty percent of patients were female, mean age was 53.6 (S.D.=15.7) years.
      Primary indication for acupuncture was low back pain (45%), headache (36%), and
      osteoarthritis (12%). Median time since the initial diagnosis was 3 years. 8.4
      (S.D.=3.0) acupuncture sessions (body acupuncture) were administered on average.
      In 28% a concomitant treatment was reported. Effectiveness of acupuncture was
      rated by physicians in 22% of the patients as marked, in 54% as moderate, in 16%
      as minimal and in 4% as poor (unchanged). In 8% of the patients mild adverse
      reactions were reported, severe side effects occurred in 13 patients (0.003%).
      Orthopaedists rated the effectiveness of acupuncture lower, showing shortest time
      for face-to-face contact with the patient. More acupuncture training did not
      correspond to better therapeutic effect assessed by physicians. CONCLUSIONS:
      Acupuncture proved a highly demanded treatment option for chronic pain conditions
      within the German research program. Results indicate that acupuncture provided by
      qualified therapists is safe, and patients benefited from the treatment.

PMID- 18054726
TI  - Neural activities in human somatosensory cortical areas evoked by acupuncture
      stimulation.
AB  - OBJECTIVES: To investigate neural representation evoked by acupuncture from human
      somatosensory cortices, especially from primary (SI) and secondary (SII)
      somatosensory areas. DESIGN AND SETTING: Neuroimaging study - Blood-oxygenation
      level-dependent (BOLD) functional MRI was performed during acupuncture on LI4
      (n=12 healthy participants). Sham acupuncture and innocuous tactile stimulation
      were also applied on the same acupuncture site as control comparisons. OUTCOME
      MEASURES: Responsive neural substrates were visualized and identified based on
      both individual and group-level surface activation maps. RESULTS: Discrete
      regions within the precentral gyrus (area 4) and the fundus of the central sulcus
      (area 3a) were selectively activated during the real acupuncture stimulation. In
      SII, the activation was extended in a postero-inferior direction to the fundus of
      the lateral sulcus. CONCLUSION: This specific pattern of acupuncture-related
      activation indicates that deep tissue stimulation (as seen in area 3a activation)
      and concurrent processing of sensory stimulation (as seen in activation in SII)
      may mediate neural responses to manual acupuncture.

PMID- 18054728
TI  - The professionalization of Western herbalists: response to new product
      regulations in Canada.
AB  - New Canadian Natural Health Products regulations (NHP regulations) came into law
      January 1st, 2004 and will be implemented over 6 years. These regulations have
      the potential to impact a variety of stakeholders, in particular complementary
      and alternative medicine (CAM) practitioners. In this article, we document
      Canadian Western herbalist leaders' responses to the new regulations, so as to
      provide insight into how new healthcare policy serves as a stimulus for the
      organization of an emerging healthcare profession. The data are derived from key
      informant interviews with Western herbalist leaders in Canada (n=9). The NHP
      regulations include "good manufacturing practices" and Western herbalist leaders
      are concerned that many small companies, often owned and run by Western
      herbalists, will find the regulations too costly to implement, causing them to
      reduce the number and diversity of products they manufacture, or go out of
      business all together. Furthermore, lack of availability of whole plant products
      could severely restrict the practice of Canadian Western herbalists. In response
      to this challenge, herbalists are attempting to (i) organize as a more cohesive
      group, (ii) define their unique body of knowledge and (iii) increase the
      perceived legitimacy of their practices in the eyes of the public, conventional
      healthcare practitioners, and regulators, in an attempt to protect their unique
      practices. An examination of the findings reveals the extent to which external
      factors (i.e., the new NHP regulations) both provoke and shape the
      professionalization of this group of healthcare practitioners.

PMID- 18054727
TI  - Neuroendocrinological effects of acupuncture treatment in patients with irritable
      bowel syndrome.
AB  - OBJECTIVES: Quality of life (QoL) improvement in patients with irritable bowel
      syndrome (IBS) during acupuncture (AC) treatment seems to be due to a placebo
      effect. The aim was to explore if acupuncture has some specific influence on the
      neuroendocrinic and autonomic nervous system (ANS). DESIGN/SETTING: Patients with
      IBS were randomly assigned to receive either acupuncture (AC) or sham acupuncture
      (SAC) using the so-called "Streitberger needle". QoL was measured with the
      functional quality of life diseases quality of life questionnaire (FDDQL) and SF
      36. The effect on ANS was evaluated by measuring salivary cortisol and by
      cardiovascular responses on a tilt table before and after 10 AC treatments.
      Complete data sets of tilt table and salivary morning cortisol were available for
      9 patients in the AC and 12 in SAC group. RESULTS: QoL increased in both groups
      (p=0.001) with no group differences. Salivary cortisol decreased in all groups
      (F=10.55; p=0.006). However, the decrease was more pronounced in the AC group
      (F=4.07; p=0.033) (ANOVA repeated measures model). Heart rate response decreased
      during orthostatic stress in the AC group while it increased in the SAC group
      (F=9.234; p=0.005), indicating an increased parasympathetic tone in the AC group.
      Improvement of pain was positively associated with increased parasympathetic tone
      in the AC group (F=10.1; p=0.006), but not in the SAC group. CONCLUSIONS: The
      acupuncture specific physiological effects are in contrast to the unspecific
      improvement of QoL in both AC and SAC groups. Thus, different mechanisms seem to
      be involved in placebo and real-acupuncture driven improvements. The specific
      mechanism of action of acupuncture on the ANS remains unclear and deserves
      further evaluation.

PMID- 18054729
TI  - Psychological response in spinal manipulation (PRISM): a systematic review of
      psychological outcomes in randomised controlled trials.
AB  - BACKGROUND: The most important risk factors for back and neck pain are
      psychosocial. Nevertheless, systematic reviews of spinal manipulation have
      concentrated on pain and spine related disability, and ignored psychological
      outcomes. OBJECTIVE: To assess whether spinal manipulation was effective in
      improving psychological outcome. DESIGN: Systematic review of randomised
      controlled trials (RCTs). METHODS: RCTs were identified by searching Medline,
      CINAHL, Embase, CENTRAL, AMED, PsycINFO until November 2005. Trials reporting
      psychological outcomes including the mental health components of generic outcomes
      were extracted, and combined where appropriate in meta-analyses. RESULTS: One
      hundred and twenty nine RCTs of spinal manipulation were identified; 12 had
      adequately reported psychological outcomes. Six trials with a verbal intervention
      comparator were combined in a meta-analysis, and found a mean benefit from spinal
      manipulation equivalent to 0.34 of the population standard deviation (S.D.) [95%
      confidence interval (CI) 0.23-0.45] at 1-5 months; 0.27 of the S.D. [95% CI 0.14
      0.40] at 6-12 months. Eight trials with a physical treatment comparator were
      combined in a meta-analysis and found a mean benefit of 0.13 of the S.D. [95% CI
      0.01-0.24] in favour of manipulation at 1-5 months; 0.11 of the S.D. [95% CI 
      0.02 to 0.25] at 6-12 months. CONCLUSIONS: There was some evidence that spinal
      manipulation improved psychological outcomes compared with verbal interventions.

PMID- 18054730
TI  - The need for traditional Chinese medicine morbidity research.
AB  - Traditional Chinese medicine (TCM) has long justified its practice on empirical
      phenomenology. Questions remain, however, as to the legitimacy of this approach
      and its relevance to TCM practice and educational developments in the 21st
      century. General medical practice (GMP) has used practice-based data collected
      over the past 25 years to develop relevant medical curriculum and enhance patient
      care. As TCM becomes ever more incorporated into Western educational and health
      systems, it too must concern itself with providing a solid evidence base to be
      used in enhancing patient care and educational curriculum. Computer generated
      data related to patient problems or problem complexes abstracted from TCM
      clinical records can provide the basis for practitioner development and the
      enhancement of training programs that will lead to improvements in patient care.
      Such locally valid and representative data can also be used to inform research
      programs, public policy and evidence-based commissioning. The key to developing
      such systems is standardising TCM terminology and data collection protocols.

PMID- 18054732
TI  - Incretin hormone mimetics and analogues in diabetes therapeutics.
AB  - The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) are physiological gut peptides with insulin
      releasing and extrapancreatic glucoregulatory actions. Incretin
      analogues/mimetics activate GLP-1 or GIP receptors whilst avoiding physiological
      inactivation by dipeptidyl peptidase 4 (DPP-4), and they represent one of the
      newest classes of antidiabetic drug. The first clinically approved GLP-1 mimetic
      for the treatment of type-2 diabetes is exenatide (Byetta/exendin) which is
      administered subcutaneously twice daily. Clinical trials of liraglutide, a GLP-1
      analogue suitable for once-daily administration, are ongoing. A number of other
      incretin molecules are at earlier stages of development. This review discusses
      the various attributes of GLP-1 and GIP for diabetes treatment and summarises
      current clinical data. Additionally, it explores the therapeutic possibilities
      offered by preclinical agents, such as non-peptide GLP-1 mimetics, GLP-1/glucagon
      hybrid peptides, and specific GIP receptor antagonists.

PMID- 18054733
TI  - DPP-4 inhibitors.
AB  - Inhibition of dipeptidyl peptidase 4 (DPP-4) is a novel treatment for type-2
      diabetes. DPP-4 inhibition prevents the inactivation of glucagon-like peptide 1
      (GLP-1), which increases levels of active GLP-1. This increases insulin secretion
      and reduces glucagon secretion, thereby lowering glucose levels. Several DPP-4
      inhibitors are in clinical development. Most experience so far has been with
      sitagliptin (Merck; approved by the FDA) and vildagliptin (Novartis; filed).
      These are orally active compounds with a long duration, allowing once-daily
      administration. Both sitagliptin and vildagliptin improve metabolic control in
      type-2 diabetes, both in monotherapy and in combination with metformin and
      thiazolidinediones. A reduction in HbA(1c) of approximately 1% is seen in studies
      of DPP-4 inhibition of up to 52 weeks' duration. DPP-4 inhibition is safe and
      well tolerated, the risk of hypoglycaemia is minimal, and DPP-4 inhibition is
      body-weight neutral. DPP-4 inhibition is suggested to be a first-line treatment
      of type-2 diabetes, particularly in its early stages in combination with
      metformin. However, the durability and long-term safety of DPP-4 inhibition
      remain to be established.

PMID- 18054734
TI  - Cannabinoid-1 receptor antagonists in type-2 diabetes.
AB  - Type-2 diabetes is closely related to abdominal obesity and is generally
      associated with other cardiometabolic risk factors, resulting in a risk of major
      cardiovascular disease. Several animal and human observations suggest that the
      endocannabinoid system is over-active in the presence of abdominal obesity and/or
      diabetes. Both central and peripheral endocannabinoid actions, via the activation
      of CB1 receptors, promote weight gain and associated metabolic changes.
      Rimonabant, the first selective CB(1) receptor blocker in clinical use, has been
      shown to reduce body weight, waist circumference, triglycerides, blood pressure,
      insulin resistance index and C-reactive protein levels, and to increase high
      density lipoprotein (HDL) cholesterol and adiponectin concentrations in both non
      diabetic and diabetic overweight/obese patients. In addition, a 0.5-0.7%
      reduction in HbA1c levels was observed in metformin- or sulphonylurea-treated
      patients with type-2 diabetes and in drug-naive diabetic patients. Almost half of
      the metabolic changes, including HbA1c reduction, could not be explained by
      weight loss, suggesting that there are direct peripheral effects. Rimonabant was
      generally well-tolerated, and the safety profile was similar in diabetic and non
      diabetic patients, with a higher incidence of depressed mood disorders, nausea
      and dizziness. In conclusion, the potential role of rimonabant in
      overweight/obese patients with type-2 diabetes and at high risk of cardiovascular
      disease deserves much consideration.

PMID- 18054735
TI  - Inhaled insulin.
AB  - Inhaled insulin has attractive pharmacodynamic properties with a fast onset of
      action which should lead to improved postprandial blood glucose concentrations.
      Comparisons with regular subcutaneous (sc) insulin in clinical studies, however,
      showed lower fasting blood glucose concentrations. Overall, clinical efficacy of
      inhaled insulin was comparable to that of regular sc insulin. Treatment with
      inhaled insulin was safe and well tolerated, with slight and reversible changes
      in lung function parameters and a rise in insulin antibodies (not associated with
      any clinical or safety parameters) as main adverse effects. Treatment
      satisfaction in open-label studies was higher with inhaled than with sc insulin,
      indicating that inhaled insulin might help to overcome one of the major hurdles
      of diabetes therapy, i.e. a timely initiation of insulin therapy. The first
      inhaled insulin formulation was approved in the US and Europe in January 2006,
      but some countries granted reimbursement only for selected patients, or did not
      reimburse treatment with inhaled insulin at all because of the high treatment
      costs. These are due to the rather low bioavailability of approximately 8-15%.
      Therefore, further research is needed to improve the bioavailability of inhaled
      insulin: e.g. through optimization of the inhaler, the insulin formulation, or
      the inhalation technique. In view of the potential for further improvement,
      inhaled insulin may become a very attractive alternative to sc insulin, in
      particular in patients in whom insulin therapy has to be initiated and/or
      intensified.

PMID- 18054736
TI  - PKC inhibition and diabetic microvascular complications.
AB  - In patients with diabetes, the hyperglycaemia is known to promote high levels of
      diacylglycerol which activates protein kinase C (PKC) in the vascular tissues and
      leads to production of vascular endothelial growth factor (VEGF) in the retina.
      PKC activation is likely to play a key role in diabetic microvascular
      complications, particularly changes in vascular permeability and ischaemia in the
      retina. A new potential therapeutic agent, the PKC-beta inhibitor ruboxistaurin,
      has been studied in animal and human clinical trials in diabetic microvascular
      disease, particularly in patients with diabetic retinopathy. The mechanism of
      action of PKC and the results of these trials are discussed in this review.
      Ruboxistaurin shows promise as an oral treatment for diabetic retinopathy. The
      trials have demonstrated a significant reduction in visual loss and need for
      laser treatment in patients with moderate to severe diabetic retinopathy over a 3
      year period. There have been no significant concerns over safety or the side
      effects profile in the clinical trials. Ruboxistaurin currently has approvable
      status pending further randomized trials defined by the US Food and Drug
      Administration (FDA).

PMID- 18054737
TI  - New hepatic targets for glycaemic control in diabetes.
AB  - Type-2 diabetes is associated with impaired glucose clearance by the liver in the
      postprandial state, and with elevated glucose production in the post-absorptive
      state. New targets within the liver are currently being investigated for
      development of antihyperglycaemic drugs for type-2 diabetes. They include
      glucokinase, which catalyses the first step in glucose metabolism, the glucagon
      receptor, and enzymes of gluconeogenesis and/or glycogenolysis such as glucose 6
      phosphatase, fructose 1,6-bisphosphatase and glycogen phosphorylase. Preclinical
      studies with candidate drugs on animal models or cell-based assays suggest that
      these targets have the potential for pharmacological glycaemic control. Data from
      clinical studies is awaited. Further work is required for better understanding of
      the implications of targeting these sites in terms of possible side-effects or
      tachyphylaxis. The advantage of combined targeting of two or more sites within
      the liver for minimizing side-effects and tachyphylaxis caused by single-site
      targeting is discussed.

PMID- 18054738
TI  - Modulation of glucocorticoid action and the treatment of type-2 diabetes.
AB  - The global epidemic of obesity and type-2 diabetes has heightened the need to
      understand the mechanisms that contribute to its pathogenesis and also to design
      and trial novel treatments. Patients with glucocorticoid (GC) excess--'Cushing's
      syndrome'--are phenotypically similar to patients with simple obesity. As such,
      much research has focused on the manipulation of local GC action as a therapeutic
      strategy. The majority of the classical actions of GCs are mediated via
      activation of the glucocorticoid receptor (GR). 11beta-Hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) converts inactive cortisone to cortisol and
      therefore amplifies local GC action. There is now a wealth of data from rodent
      and clinical studies implicating this conversion in the pathogenesis of obesity,
      type-2 diabetes, and the metabolic syndrome. Selective 11beta-HSD1 inhibitors
      (selective in that they block the activity of 11beta-HSD1 and not 11beta-HSD2
      which inactivates cortisone to cortisol in mineralocorticoid target tissues) are
      currently in development although not yet available for use in clinical studies.
      Rodent studies utilizing these compounds have shown dramatic improvements in
      insulin sensitivity as well as improvements in lipid profiles and atherogenesis.
      A further experimental approach has been to design drugs that antagonize GR
      activation, and again these compounds appear to improve insulin sensitivity and
      lower glucose production rates. The key test for both of these research
      strategies is whether they will translate into clinical studies, and results from
      these trials are now eagerly awaited.

PMID- 18054739
TI  - Inhibition of the protein tyrosine phosphatase PTP1B: potential therapy for
      obesity, insulin resistance and type-2 diabetes mellitus.
AB  - The global epidemic of obesity and type-2 diabetes mellitus (T2DM) has
      highlighted the need for new therapeutic approaches. The association of insulin
      resistance with these disorders and the knowledge that insulin receptor signaling
      is mediated by tyrosine (Tyr) phosphorylation have generated great interest in
      the regulation of the balance between Tyr phosphorylation and dephosphorylation.
      Several protein Tyr phosphatases (PTPs) have been implicated in the regulation of
      insulin action, with the most convincing data for PTP1B. Murine models targeting
      PTP1B, PTP1B(-/-)mice, demonstrate enhanced insulin sensitivity without the
      weight gain seen with other insulin sensitizers such as peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists, probably due to a second action of
      PTP1B as a negative regulator of leptin signaling. Despite intensive efforts and
      recent progress, a safe, selective and efficacious PTP1B inhibitor has yet to be
      identified.

PMID- 18054740
TI  - Potential therapies based on antidiabetic peptides.
AB  - Since adipose tissue was shown to be more than a storage organ, the many
      cytokines it produces have been identified, along with their roles in energy
      homeostasis, appetite, and insulin resistance. Concurrently, numerous gut
      hormones with a diversity of effects have been discovered. They include, amongst
      many others, peptide YY, ghrelin and oxyntomodulin. As these peptides have been
      investigated, the potential for their use as novel anti-obesity and antidiabetic
      therapies has been realized. In this chapter we describe the actions of four of
      the peptides that have been proposed as the basis for promising new therapies for
      diabetes: leptin, adiponectin, obestatin and peptide YY. They each have an effect
      on appetite and, directly or indirectly, on glucose metabolism. We synthesize
      available data for these peptides and consider the therapeutic potential of each.

PMID- 18054741
TI  - Pharmaco-economic issues for diabetes therapy.
AB  - A systematic review was undertaken to analyse pharmaco-economic issues in
      diabetes, with evidence selected on the basis of relevance and immediacy.
      Pharmaco-economics in diabetes primarily relates to making choices about
      antidiabetic pharmaceuticals, and this is being influenced by global trends.
      Trends include increasing numbers of patients with diabetes, with increasing
      costs of caring for people with diabetes, and an ever-present focus on the costs
      of pharmaceuticals which are predicted to increase as the pace of development of
      new medications parallels the increasing incidence of the condition. These
      developments have influenced the demand for health care in diabetes in the last
      decade, and will continue to determine this in the coming decade. Recent national
      experiences are cited to illustrate current issues and to focus specifically upon
      the challenges facing a raft of new diabetes treatment options now hitting the
      marketplace, although supported by fewer completed long-term trials. It can be
      anticipated that these newer agents will be appraised for their cost
      effectiveness or value for money. Economic analyses for some of the new
      technologies are summarized; in general, the peer-reviewed publications using
      well-accepted and validated models have reported that these technologies are cost
      effective. Endorsement of any technology in a national setting is not awarded
      simply because the incremental cost-effectiveness ratio (ICER) falls below the
      threshold regarded as value for money. In most national observations the
      reviewers expressed concerns about assumptions used in economic modelling which
      resulted in the ICERs being deemed optimistic at best, generally highly
      uncertain, and resulting in the cost-effectiveness appearing better than it
      really would be in clinical practice. This has often led to the authorities
      concluding that the price advantage of new technologies over comparators could
      not be justified, essentially leading to restrictions in use compared to their
      licence. In general, a paucity of robust evidence on longer-term outcome data
      together with a lack of health-related quality of life (HRQOL) data collected in
      a reliable manner in appropriate patients and amenable to utility (and hence
      quality adjusted life year or QALY) estimation have resulted in problems for
      these new drugs at the so-called fourth (cost-effectiveness) hurdle. In the light
      of these findings, the implications for generating credible fit-for-purpose cost
      effectiveness analyses of new technologies in diabetes are discussed. Throughout
      this chapter, the interested reader is referred to a number of excellent review
      articles for further details.

PMID- 18054742
TI  - PPAR agonists: multimodal drugs for the treatment of type-2 diabetes.
AB  - Patients with type-2 diabetes mellitus (T2DM) are considered to be at
      particularly high risk for cardiovascular disease. Over the last decade, the
      members of the peroxisome proliferator-activated receptor (PPAR) subfamily of
      nuclear receptors have emerged as valuable pharmacological targets whose
      activation can normalize metabolic dysfunctions and reduce some cardiovascular
      risk factors associated with T2DM. PPARalpha agonists, such as the fibrates, can
      correct dyslipidemia. PPARgamma agonists, such as the thiazolidinediones, act as
      insulin sensitizers and improve insulin resistance in patients with T2DM. Because
      of restricted potency and certain side-effects of PPAR agonists, as well as the
      increasingly epidemic incidence of T2DM, there is a real need for the development
      of selective PPAR agonists with improved clinical efficacy. This chapter focuses
      on the PPAR agonists currently used in the clinic, as well as on the discovery
      and development of the next generation of PPAR agonists.

PMID- 18054743
TI  - Eosinophilic esophagitis and Barrett's esophagus with dysplasia.

PMID- 18054744
TI  - Esophageal intramural pseudodiverticulosis.

PMID- 18054747
TI  - Feeding alternatives in patients with dementia: examining the evidence.
AB  - Percutaneous endoscopic gastrostomy tubes are being placed with increasing
      frequency in the United States among elderly patients with dementia. Health care
      providers believe there may be long-term benefits for enteral feeding in this
      population, yet previous study of this topic has failed to yield any convincing
      evidence to support this hypothesis. In this study, we review the evidence
      regarding outcomes for artificial enteral feeding in older individuals with
      dementia. We found that there is a lack of evidence supporting artificial feeding
      in the specific outcomes of survival, pressure ulcers, nutrition, and aspiration
      pneumonia. A brief discussion regarding hand feeding is included. The data
      suggest that hand feeding may be a viable alternative to tube feeding in elderly
      patients with dementia, although a direct comparison trial of the 2 interventions
      is lacking.

PMID- 18054748
TI  - Sore throat and a red hypopharynx: is it reflux?

PMID- 18054749
TI  - The burden of inflammatory bowel disease in the United States: a moving target?

PMID- 18054750
TI  - Use of acid-suppressing drugs and the risk of bacterial gastroenteritis.
AB  - BACKGROUND & AIMS: Gastric acid is a defense mechanism against gastrointestinal
      infections caused by ingested bacteria. Studies have suggested that the use of
      acid-suppressing drugs may increase the risk of gastroenteritis (GE). METHODS:
      Patients aged 20-74 years with an episode of acute bacterial GE (n = 6414) were
      identified. A control group from the same study population without a diagnosis of
      GE (n = 50,000) was frequency-matched by age, sex, and calendar year to the case
      group. Unconditional logistic regression was used to calculate the adjusted
      relative risk (RR) of GE in patients using proton pump inhibitors (PPIs) or
      histamine-2 receptor antagonists (H2RAs). RESULTS: Current use of PPIs was
      associated with an increased risk of bacterial GE compared with nonuse,
      regardless of the treatment duration (RR, 2.9; 95% confidence interval [CI], 2.5
      3.5), whereas no association was observed with H2RA use (RR, 1.1; 95% CI, 0.9
      1.4). Doubling the PPI dose further increased the risk of developing bacterial GE
      (RR, 5.0; 95% CI, 2.7-9.3). The effect of PPI use did not vary significantly with
      regard to treatment indication. The increased risk associated with PPI use was
      similar for both omeprazole (RR, 3.0; 95% CI, 2.5-3.7) and lansoprazole (RR, 2.1;
      95% CI, 1.4-3.0), whereas neither cimetidine nor ranitidine showed any increased
      risk. Campylobacter (n = 4124) and Salmonella (n = 1885) were the 2 species most
      frequently responsible for GE episodes in the case group. When analyzed
      separately, both species reproduced the increased risk associated with PPI use
      and not H2RA use. Clostridium GE cases were rare (n = 31). CONCLUSIONS: This
      study suggests that gastric acid suppression induced by PPIs but not H2RAs is
      associated with an increased risk of Campylobacter and Salmonella GE.

PMID- 18054751
TI  - Clinical course in Crohn's disease: results of a Norwegian population-based ten
      year follow-up study.
AB  - BACKGROUND & AIMS: Most studies concerning the clinical course in CD are
      retrospective or based on selected patient groups. Our aim was to assess the
      course of CD in a prospective population-based follow-up study and to identify
      possible prognostic risk factors for complications on the basis of information
      obtained at initial diagnosis. METHODS: From 1990-1994, a population-based cohort
      of 843 new cases of inflammatory bowel disease was recruited in South-Eastern
      Norway. The cohort was systematically followed up at 1, 5, and 10 years after
      diagnosis. RESULTS: Of 237 patients classified as CD, 197 completed the 10 years
      of follow-up, 18 died, and 22 were lost to follow-up. The cumulative relapse rate
      during the first 10 years was 90% (95% confidence interval, 86%-94%), and the
      cumulative probability of surgery was 37.9% (95% confidence interval, 31.4%
      44.4%). Terminal ileal location (P < .001), stricturing (P = .004), penetrating
      behavior (P < .001), and age younger than 40 years (P = .03) at diagnosis were
      independent risk factors for subsequent surgery. A total of 53% (n = 105) of the
      patients had developed stricturing or penetrating disease at 10 years. A large
      proportion of patients (44%) were in clinical remission during the last 5 years
      of follow-up. CONCLUSIONS: The prognosis for CD seems better than previously
      reported. The probability of surgery was low, and fewer than expected developed
      complicated disease behavior. Nevertheless, the cumulative relapse rate of 90%
      and the finding of prognostic risk factors for subsequent surgery might call for
      attention to early effective medical treatment strategies.

PMID- 18054752
TI  - What is the value of computered tomography colonography in patients screening
      positive for fecal occult blood? A systematic review and economic evaluation.
AB  - BACKGROUND & AIMS: Computerized tomography colonography (CTC) is a highly
      accurate test for the detection of colorectal polyps and cancers and has been
      proposed as a potential alternative to colonoscopy. Bowel cancer screening using
      fecal occult blood testing (FOBT) and follow-up diagnostic colonoscopy is an
      effective intervention that currently is being implemented in screening programs
      internationally. Because of high false-positive rates for FOBT, concerns have
      been raised about patient uptake and access to colonoscopy services. This study
      assessed the value of CTC as an alternative to colonoscopy in FOBT-positive
      individuals. METHODS: A systematic review of studies comparing the accuracy of
      CTC and colonoscopy for the detection of lesions 10 mm or greater and cancers in
      nonscreening populations was conducted. A modeled economic analysis was
      undertaken to assess cost per life-year saved. RESULTS: Five eligible studies
      were identified. Pooled sensitivity and specificity for the detection of lesions
      10 mm or greater were 63% (95% confidence interval [CI], 55%-71%) and 95% (95%
      CI, 94%-97%) for CTC, and 95% (95% CI, 90%-98%) and 99.8% (95% CI, 99.5%-100%)
      for colonoscopy, respectively (3 studies). Pooled sensitivity and specificity for
      the detection of cancer were 89% (95% CI, 70%-98%) and 97% (95% CI, 95%-98%) for
      CTC, and 96% (95% CI, 80%-100%) and 99.7% (95% CI, 99%-100%) for colonoscopy,
      respectively (3 studies). The base case economic analysis showed that CTC is less
      effective and more costly than colonoscopy. At a low prevalence of polyps,
      sensitivity analysis found CTC was less effective and less costly than
      colonoscopy; if CTC was more sensitive than colonoscopy, CTC was more effective,
      at higher cost. CONCLUSIONS: Overall, CTC appears less accurate, less effective,
      and potentially more costly than colonoscopy in individuals with a positive FOBT.

PMID- 18054756
TI  - Environmental conditions in early life influence ageing rates in a wild
      population of red deer.

PMID- 18054753
TI  - Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in
      the liver and predict treatment response.
AB  - BACKGROUND & AIMS: We aimed to evaluate serum hepatitis B surface antigen (HBsAg)
      quantitation as a surrogate marker for covalently closed circular DNA (cccDNA)
      and intrahepatic hepatitis B virus (HBV) DNA, and as a predictor of sustained
      virologic response to peginterferon and lamivudine combination therapy. METHODS:
      Twenty-six hepatitis B e antigen-positive chronic hepatitis B patients receiving
      combination treatment of 32-week peginterferon alfa-2b and 2-year lamivudine were
      studied. All patients had liver biopsy before and after treatment for cccDNA and
      intrahepatic HBV DNA measurement. Sustained virologic response was defined as
      sustained hepatitis B e antigen seroconversion and HBV DNA less than 10,000
      copies/mL at the end of treatment until 1 year posttreatment. RESULTS: Seven
      patients developed sustained virologic response. At baseline, HBsAg correlated
      well with both log (cccDNA) (r = 0.54, P = .004) and log [total intrahepatic HBV
      DNA] (r = 0.43, P = .028). The median reduction of HBsAg was 1287 IU/mL (range,
      12,223-26,763 IU/mL). Reduction of HBsAg has good correlation with reduction in
      log [cccDNA] (r = 0.68, P < .0001) and reduction in log [total intrahepatic HBV
      DNA] (r = 0.65, P < .0001). Patients with lower baseline cccDNA, intrahepatic HBV
      DNA, and HBsAg level but not serum HBV DNA level tend to develop sustained
      virologic response. A baseline HBsAg level of less than 10,000 IU/mL had
      sensitivity, specificity, and positive and negative predictive values for
      sustained virologic response of 86%, 56%, 43%, and 92%, respectively.
      CONCLUSIONS: Serum HBsAg levels correlate well with the cccDNA and intrahepatic
      HBV DNA. Low pretreatment HBsAg is better than HBV DNA to predict good response
      to peginterferon and lamivudine treatment.

PMID- 18054757
TI  - Generation of uniform fly retinas.

PMID- 18054758
TI  - Working memory of numerals in chimpanzees.

PMID- 18054759
TI  - Developmental biology: hippo promotes posterior patterning by preventing
      proliferation.
AB  - The Hippo pathway is a potent regulator of tissue growth. Two recent studies
      report a new function of the pathway in the differentiation of the follicular
      epithelium during Drosophila oogenesis.

PMID- 18054760
TI  - Animal cognition: time flies when chimps are having fun.
AB  - Chimpanzees, like children, actively distract themselves to cope with waiting for
      a desired but delayed reward. Self-control may thus be a capacity we share with
      our nonhuman primate relatives.

PMID- 18054761
TI  - Motion processing: where the medium is the message.
AB  - The primate retina serves up three channels for visual entertainment, of which
      just one is used for the primary analysis of motion. A prominent, unique class of
      neuron has a dominant role in transmission from cortical area V1.

PMID- 18054762
TI  - Genital Evolution: blurring the battle lines between the sexes.
AB  - The rapid, divergent evolution of genitalia is a general trend in animals and
      likely influenced by sexual selection. Contrary to previous ideas, an intriguing
      new study suggests that sexual selection by sexual conflict can promote the
      evolution of both male and female genitalia.

PMID- 18054763
TI  - Evolution of protein expression: new genes for a new diet.
AB  - A new study identifies gene duplication of a salivary enzyme as a recent
      adaptation to changes in diet among human populations, highlighting the diverse
      ways that gene regulation can evolve.

PMID- 18054764
TI  - Organelle motility: running on unleadened.
AB  - The study of fish and amphibian melanocytes has yielded a wealth of information
      on the regulation of microtubule- and actin-based motor proteins involved in
      organelle transport. A new zebrafish mutant provides further insight into how the
      actions of these motors are coordinated in vivo.

PMID- 18054765
TI  - Sensory ecology: see me, hear me.
AB  - The animal world is replete with vibrant colours: these are often used as display
      signals and selection has solved a fundamental problem in information transfer by
      enhancing the detectability of these signals against the backgrounds on which
      they are perceived by the particular sensory systems of their receivers.

PMID- 18054766
TI  - Signal transduction: networks and integrated circuits in bacterial cognition.
AB  - Signal transduction systems that mediate adaptive changes in gene expression to
      specific sensory inputs have been well characterized. Recent studies have focused
      on mechanisms that allow crosstalk between different information-processing
      modalities.

PMID- 18054767
TI  - Motor learning: passing a skill from one hand to the other.
AB  - A recent study has provided surprising new insights into the neural mechanisms
      underlying our ability to transfer a learned motor skill from one hand to the
      other.

PMID- 18054768
TI  - Nocturnal bees.

PMID- 18054769
TI  - Columbines.

PMID- 18054770
TI  - Termites.

PMID- 18054771
TI  - Aptamer biosensor for protein detection using gold nanoparticles.
AB  - Combining gold nanoparticles (GNPs) as fluorescence quencher and aptamer as
      probe, we have developed protein biosensors by using DNA-modified GNPs. We
      examined how the experimental design, such as the type of interaction between DNA
      strands and GNPs, temperature, and microenvironment of aptamer, influences the
      recognition ability of the biosensor. Under our experimental conditions, the
      recognition of protein by the complex of dye-labeled DNA hybridized with aptamer
      that is immobilized on GNPs (Ap-Im-GNPs) shows the best character in protein
      detection.

PMID- 18054772
TI  - Use of layer silicate for protein crystallization: effects of Micromica and
      chlorite powders in hanging drops.
AB  - Two kinds of layer silicate powder, Micromica and chlorite, were used to aid
      protein crystallization by the addition to hanging drops. Using appropriate
      crystallization buffers, Micromica powder facilitated crystal growth speed for
      most proteins tested in this study. Furthermore, the addition of Micromica powder
      to hanging drops allowed the successful crystallization of lysozyme, catalase,
      concanavalin A, and trypsin even at low protein concentrations and under buffer
      conditions that otherwise would not generate protein crystals. Except for
      threonine synthase and apoferritin, the presence of chlorite delayed
      crystallization but induced the formation of large crystals. X-ray analysis of
      thaumatin crystals generated by our novel procedure gave better quality data than
      did that of crystals obtained by a conventional hanging drop method. Our results
      suggest that the speed of crystal growth and the quality of the corresponding X
      ray data may be inversely related, at least for the formation of thaumatin
      crystals. The effect of Micromica and chlorite powders and the application of
      layer silicate powder for protein crystallization are discussed.

PMID- 18054773
TI  - Synthesis of functional proteins using Escherichia coli extract entrapped in
      calcium alginate microbeads.
AB  - In this report, we describe the construction and analysis of a cell-free protein
      synthesis system immobilized in calcium alginate microbeads. When incubated in a
      feeding solution that contained amino acids and other low-molecular-weight
      substrates, the microbeads transcribed and translated coimmobilized DNA into
      functional proteins. Protein synthesis continued for more than 15 h with the
      diffusional supply of substrates and removal of by-products. In addition,
      functional proteins were generated from PCR-amplified genes as efficiently as
      from plasmid, suggesting that these cell-like microbeads could be used for
      functional screening of genomic libraries.

PMID- 18054774
TI  - Capillary electrophoresis for the quality control of chondroitin sulfates in raw
      materials and formulations.
AB  - Exogenous administration of chondroitin sulfate (CS) is widely practiced for the
      treatment of osteoarthritis, although the efficacy of this treatment has not been
      completely established by clinical studies. A reason for the inconsistency of the
      results may be the quality of the CS preparations, which are commercially
      available as dietary supplements. In this article, we describe the development of
      a new method of capillary electrophoresis (CE) for the quantification of CS
      concentrations, screening for other glycosaminoglycan or DNA impurities and
      determination of hyaluronan impurities in CS raw materials, tablets, hard
      capsules, and liquid formulations. Analysis is performed within 12 min in bare
      fused silica capillaries using reversed polarity and an operating phosphate
      buffer of low pH. The method has high sensitivity (lower limit of quantitation
      [LLOQ] values of 30.0 microg/ml for CS and 5.0 microg/ml for hyaluronan), high
      precision, and accuracy. Analysis of 11 commercially available products showed
      the presence of hyaluronan impurities in most of them (up to 1.5%). CE analysis
      of the samples after treatment with chondroitinase ABC and ACII, which
      depolymerize the chains to unsaturated disaccharides, with a previously described
      method (Karamanos et al., J. Chromatogr. A 696 (1995) 295-305) confirmed the
      results of hyaluronan determination and showed that the structural
      characteristics (i.e., disaccharide composition) of CS are very different,
      showing the different species or tissue origin and possibly affecting the
      therapeutic outcome.

PMID- 18054775
TI  - Inhibition of squalene synthase upregulates PCSK9 expression in rat liver.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in
      cholesterol metabolism by enhancing the degradation of the LDL receptor protein
      in the liver. It has previously been shown that administration of zaragozic acid
      A (ZA), a potent inhibitor of squalene synthase, also significantly increases the
      rate of degradation of hepatic LDL receptor protein. Thus, we decided to
      determine whether ZA administration might act to up regulate hepatic expression
      of the rat PCSK9 gene. Administration of ZA resulted in increased PCSK9 mRNA and
      protein levels in rat liver surprisingly in concert with an increase in hepatic
      LDL receptor mRNA levels, LDL receptor protein turnover, and decreased serum
      cholesterol levels. These observations suggest an involvement of PCSK9 in hepatic
      LDL receptor protein degradation and perhaps, in increasing the rate of LDL
      receptor cycling resulting in lower serum cholesterol levels in response to
      cholesterol biosynthesis inhibitors.

PMID- 18054776
TI  - Molecular and functional characterization of D-3-phosphoglycerate dehydrogenase
      in the serine biosynthetic pathway of the hyperthermophilic archaeon Sulfolobus
      tokodaii.
AB  - A gene (ST1218) encoding a D-3-phosphoglycerate dehydrogenase (PGDH; EC 1.1.1.95)
      homolog was found in the genome of Sulfolobus tokodaii strain 7 by screening a
      database of enzymes likely to contribute to l-serine biosynthesis in
      hyperthermophilic archaea. After expressing the gene in Escherichia coli, the
      PGDH activity of the recombinant enzyme was assessed. Homogeneous PGDH was
      obtained using conventional chromatography steps, though during the purification
      an unexpected decline in enzyme activity was observed if the enzyme was stored in
      plastic tubes, but not in glass ones. The purified enzyme was a homodimer with a
      subunit molecular mass of about 35kDa and was highly thermostable. It preferably
      acted as an NAD-dependent D-3-phosphoglycerate (3PGA) dehydrogenase. Although
      NADP had no activity as the electron acceptor, both NADPH and NADH acted as
      electron donors. Kinetic analyses indicated that the enzyme reaction proceeds via
      a Theorell-Chance Bi-Bi mechanism. Unlike E. coli PGDH, the S. tokodaii enzyme
      was not inhibited by l-serine. In addition, both the NAD-dependent 3PGA oxidation
      and the reverse reaction were enhanced by phosphate and sulfate ions, while NADPH
      dependent 3-phosphohydroxypyruvate (PHP) reduction was inhibited. Thus S.
      tokodaii PGDH appears to be subject to a novel regulatory mechanism not seen
      elsewhere. A database analysis showed that ST1218 gene forms a cluster with
      ST1217 gene, and a functional analysis of the ST1217 product expressed in E. coli
      revealed that it possesses l-glutamate-PHP aminotransferase activity. Taken
      together, our findings represent the first example of a phosphorylated serine
      pathway in a hyperthermophilic archaeon.

PMID- 18054777
TI  - Effect of double-strand break DNA sequence on the PARP-1 NHEJ pathway.
AB  - Efficient repair of DNA double-strand breaks (DSBs) is critical for the
      maintenance of genomic integrity. In mammalian cells, DSBs are preferentially
      repaired by non-homologous end-joining (NHEJ). We have previously described a new
      DSBs microhomology end-joining pathway depending on PARP-1 and the XRCC1/DNA
      ligase III complex. In this study we analysed, with recombinant proteins and
      protein extracts, the effect of DSB end sequences: (i) on the DSB synapsis
      activity; (ii) on the end-joining activity. We report that PARP-1 DSB synapsis
      activity is independent of the DSB sequence and could be detected with non
      complementary DSBs. We demonstrate also that the efficiency of DSBs repair by
      PARP-1 NHEJ is strongly dependent on the presence of G:C base pairs at
      microhomology termini. These results highlight a new role of the PARP-1 protein
      on the synapsis of DSBs and could explain why the PARP-1 NHEJ pathway is strongly
      dependent on the DSBs microhomology sequence.

PMID- 18054778
TI  - Fragment responsible for translocation in the N-terminal domain of human
      topoisomerase I.
AB  - The N-terminal domain is a fragment that binds proteins and anchors topoisomerase
      I in the nucleolus. As a separate polypeptide, it translocates from the nucleolus
      to nucleoplasm upon camptothecin treatment. In this paper, we show that the
      translocation depends on the short fragment of the domain (residues from 1 to
      67). We also present a list of proteins that specifically bind to the fragment
      responsible for translocation.

PMID- 18054779
TI  - Unwanted intrusive images in obsessive compulsive disorders.
AB  - The nature and content of intrusive images in obsessional compulsive disorders
      (OCD) are described. They are primarily visual, usually vivid, effortless, fully
      formed, of brief duration, and remarkably stable. The persistence and changes of
      the images are described and some therapeutic possibilities considered.

PMID- 18054780
TI  - Dynamic endogenous association of neurofilament mRNAs with K-homology domain
      ribonucleoproteins in developing cerebral cortex.
AB  - The low, middle, and high molecular mass neurofilament subunit proteins (NF-L, NF
      M, and NF-H) co-polymerize to form neurofilaments (NFs). During development, NF
      subunit expression is highly regulated, and in neurodegenerative disease,
      aberrant regulation of this expression can lead to the formation of harmful
      aggregates. NF expression in both development and disease is under significant
      post-transcriptional control, but the specific ribonucleoproteins (RNPs) involved
      are only poorly understood. Previously, mass spectrometry on affinity purified
      proteins from rat brain identified three K-homology (KH) domain RNPs - hnRNP K,
      hnRNP E1, hnRNP E2 - as being capable of binding NF-M RNA. In the current study,
      to determine whether these RNPs associate with NF mRNAs endogenously, we
      performed a co-immunoprecipitation assay on homogenates of postnatal and
      developing rat cerebral cortex. We found that all three NF mRNAs indeed
      associated endogenously with these RNPs and that the degree of this association
      changed during postnatal development, a period when NF expression is under
      significant post-transcriptional control. The degree of these associations
      changed independently of the abundance of either the RNPs or the NF messages,
      indicating that the RNA-protein interactions themselves are directly regulated.
      This study is consistent with a model whereby these RNPs and NF mRNAs are
      components of a dynamic post-transcriptional regulatory module that influences
      the cytoskeletal compositions of neurons.

PMID- 18054781
TI  - The role of Slit-Robo signaling in the generation, migration and morphological
      differentiation of cortical interneurons.
AB  - Cortical interneurons in rodents are generated in the ventral telencephalon and
      migrate tangentially into the cortex. This process requires the coordinated
      action of many intrinsic and extrinsic factors. Here we show that Robo1 and Robo2
      receptor proteins are dynamically expressed throughout the period of
      corticogenesis and colocalize with interneuronal markers, suggesting that they
      play a role in the migration of these cells. Analysis of Robo mutants showed a
      marked increase in the number of interneurons in the cortices of Robo1(-/-), but
      not Robo2(-/-), animals throughout the period of corticogenesis and in adulthood;
      this excess number of interneurons was observed in all layers of the developing
      cortex. Using BrdU incorporation in dissociated cell cultures and phosphohistone
      3 labeling in vivo, we demonstrated that the increased number of interneurons in
      Robo1(-/-) mice is, at least in part, due to increased proliferation.
      Interestingly, a similar increase in proliferation was observed in Slit1(-/
      )/Slit2(-/-) mutant mice, suggesting that cell division is influenced by Slit
      Robo signaling mechanisms. Morphometric analysis of migrating interneurons in
      Robo1(-/-), Robo2(-/-) and Slit1(-/-)/Slit2(-/-), but not in Slit1(-/-) mice,
      showed a differential increase in neuronal process length and branching
      suggesting that Slit-Robo signaling also plays an important role in the
      morphological differentiation of these neurons.

PMID- 18054782
TI  - The role of gonadal hormones on opioid receptor protein density in arthritic
      rats.
AB  - The purpose of this study was to evaluate the effects of the gonadal hormones on
      the opioid receptor protein levels of Freund's adjuvant-treated (arthritic) male
      and female Lewis rats. Following a paw pressure nociception assay, the midbrain
      and spinal cord tissues were collected for comparison of mu, delta, and kappa
      opioid receptor protein levels. The effects of Freund's adjuvant-induced
      hyperalgesia resulted in significantly decreased nociception thresholds in both
      males and females, compared to vehicle treated animals in the paw pressure test.
      It was hypothesized that the presence or lack thereof of gonadal hormones would
      alter nociception, an effect temporally correlated with a change in opioid
      receptor protein expression. Nociceptive thresholds were altered by arthritis in
      both sexes, but not further altered by gonadal changes in males. A small, but
      significant increase in threshold was shown in ovariectomized females. In spite
      of the small gonadal-induced changes in the nociceptive threshold sensitivity to
      pressure, significant changes in the plasticity of the opioid system were
      observed. There was a significant increase in kappa opioid receptor protein
      levels in the spinal cord of arthritic ovariectomized females. Mu opioid receptor
      and kappa opioid receptor protein levels in the spinal cord tissue of non
      arthritic male rats were significantly higher than in arthritic rats, a
      difference eliminated by gonadectomy. Gonadectomy produced similar results in the
      mu opioid receptor protein level in the male midbrain tissue as well. Sex
      differences were observed in both the mu and kappa opioid receptor protein
      levels. The spinal cord tissue of male rats, regardless of the presence of gonads
      or arthritis displayed significantly greater levels of mu opioid receptor protein
      levels than females. The removal of gonadal hormones appears to have opposite
      effects in males and females in terms of opioid receptor proteins, but not
      nociception as quantified by the paw pressure test. The role of changes in the
      plasticity of the opioid systems in response to arthritis or gonadal hormones
      remains to be elucidated.

PMID- 18054783
TI  - Inducible IL-23p19 expression in human microglia via p38 MAPK and NF-kappaB
      signal pathways.
AB  - Activated microglia can release a variety of proinflammatory cytokines that play
      a crucial role in the pathogenesis of multiple sclerosis (MS). IL-23, a novel
      proinflammatory cytokine, is required for the induction of experimental
      autoimmune encephalomyelitis. Previously we demonstrated that IL-23 is expressed
      in MS lesions and that microglia are one cellular source of IL-23 in MS patients.
      In the present study we investigated the inducible expression and regulation of
      p19, a key subunit of IL-23, in human microglia. We demonstrated the inducible
      expression of IL-23p19 by lipopolysaccharide-stimulated microglial cells. Using
      signaling pathway-specific inhibitors, we showed that blocking p38 MAP kinase or
      NF-kappaB signaling pathway significantly reduced p19 expression in microglia.
      The regulatory role of p38 MAP kinase in p19 expression was further confirmed by
      decreased expression in microglia transduced with dominant-negative p38. We
      concluded that the p38 MAP kinase and NF-kappaB signaling pathways play an
      important role in regulation of IL-23p19 expression on human microglia, and are
      thus potential therapeutic targets in the treatment of MS.

PMID- 18054785
TI  - Comprehensive screening of acidic and neutral drugs in equine plasma by liquid
      chromatography-tandem mass spectrometry.
AB  - A multi-target high-throughput liquid chromatography-tandem mass spectrometry (LC
      MS-MS) method for the detection of low ppt to low ppb levels of anabolic
      steroids, corticosteroids, anti-diabetics, and non-steroidal anti-inflammatory
      drugs (NSAIDs) in equine plasma was developed for the purpose of doping control.
      Plasma samples were first deproteinated by addition of trichloroacetic acid.
      Drugs were then extracted by solid-phase extraction (SPE) using Bond Elut Certify
      cartridges, and the extracts were analysed by a triple-quadrupole/linear ion trap
      LC-MS-MS instrument in positive electrospray ionization (+ESI) mode with selected
      reaction monitoring (SRM) scan function. Chromatographic separation of the
      targeted drugs was achieved using a reverse phase 3.3 cm L x 2.1 mm ID, 3 microm
      particle size LC column with gradient elution. Plasma samples fortified with 66
      targeted drugs including betamethasone, boldione, capsaicin, flunisolide,
      gestrinone, gliclazide, 17alpha-hydroxyprogesterone hexanoate, isoflupredone and
      triamcinolone acetonide, etc. at low ppt to low ppb levels could be consistently
      detected. No significant matrix interference was observed at the retention time
      of the targeted ion transitions when blank plasma samples were analysed. The
      method has been validated for its extraction recoveries, precision and
      sensitivity, and is used regularly in the authors' laboratory to screen for the
      presence of these drugs in plasma samples from racehorses.

PMID- 18054786
TI  - Anion-exchange chromatography on short reversed-phase columns modified with
      amphoteric (N-dodecyl-N,N-dimethylammonio)alcanoates.
AB  - Short reversed-phase columns (50 mm x 4.6 mm Gemini C(18)) were dynamically
      coated with carboxybetaines of the general structure,
      C(12)H(25)N(+)(CH(3))(2)(CH(2))(n)COOH, namely (N-dodecyl-N,N
      dimethylammonio)undecanoate, DDMAU (n=10) and (N-dodecyl-N,N
      dimethylammonio)butyrate, DDMAB (n=3), and investigated for the separation of
      inorganic anions in ion chromatography. The role of the ionic strength of coating
      surfactant solutions on their adsorption and resultant column capacity was
      studied. The retention of inorganic anions was investigated with different
      eluents at various concentrations and pH. Interestingly, no retention for anions
      was found with pure water as the eluent, but the addition of small amounts of
      electrolytes, up to 0.1 mM, caused a sharp increase in the retention of analytes.
      The effect of increasing anion retention with an increase in eluent cation charge
      was also observed. Based on this effect a new cation charge gradient concept was
      proposed and applied to the separation of a standard mixture of anions.

PMID- 18054784
TI  - Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by
      redistribution of the actin modifying protein villin to the developing
      lamellipodia.
AB  - Autotaxin (ATX) is a potent tumor cell motogen that can produce lysophosphatidic
      acid (LPA) from lysophosphatidylcholine. LPA is a lipid mediator that has also
      been shown to modulate tumor cell invasion. Autotaxin mRNA is expressed at
      significant levels in the intestine. Likewise, LPA2 receptor levels have been
      shown to be elevated in colon cancers. The molecular mechanism of ATX/LPA-induced
      increase in intestinal cell migration however, remains poorly understood. Villin
      is an intestinal and renal epithelial cell specific actin regulatory protein that
      modifies epithelial cell migration. In this study we demonstrate that both Caco-2
      (endogenous villin) and MDCK (exogenous villin) cells, which express primarily
      LPA2 receptors, show enhanced cell migration in response to ATX/LPA. ATX and LPA
      treatment results in the rapid formation of lamellipodia and redistribution of
      villin to these cell surface structures, suggesting a role for villin in
      regulating this initial event of cell locomotion. The LPA-induced increase in
      cell migration required activation of c-src kinase and downstream tyrosine
      phosphorylation of villin by c-src kinase. LPA stimulated cell motility was
      determined to be insensitive to pertussis toxin, but was regulated by activation
      of PLC-gamma 1. Together, our results show that in epithelial cells ATX and LPA
      act as strong stimulators of cell migration by recruiting PLC-gamma 1 and villin,
      both of which participate in the initiation of protrusion.

PMID- 18054787
TI  - Analysis of benzene, toluene, ethylbenzene, xylenes and n-aldehydes in melted
      snow water via solid-phase dynamic extraction combined with gas
      chromatography/mass spectrometry.
AB  - The present study describes a method based on headspace-solid-phase dynamic
      extraction (HS-SPDE) followed by GC/MS for the qualitative and quantitative
      analysis of benzene, toluene, ethylbenzene, o-, m- and p-xylene (BTEX), and n
      aldehydes (C(6)-C(10)) in water. To enhance the extraction capability of the HS
      SPDE a new cooling device was tested that controls the temperature of the SPDE
      needle during extraction. Extraction and desorption parameters such as the number
      of extraction cycles, extraction temperature, desorption volume and desorption
      flow rate have been optimized. Detection limits for BTEX ranged from 19 ng/L
      (benzene) to 30 ng/L (m/p-xylene), while those for n-aldehydes ranged from 21
      ng/L (n-heptanal) to 63 ng/L (n-hexanal). At a concentration level of 2 microg/L,
      the relative standard deviations (RSDs) for BTEX ranged from 3.9% (benzene) to
      15.3% (ethylbenzene), while RSDs for n-aldehydes were between 6.1% (n-octanal)
      and 16.5% (n-hexanal) (n=7). Best results were obtained when the analyzed water
      samples were heated to 50 degrees C. At a water temperature of 70 degrees C GC
      responses decreased for all analyzed compounds. At a defined water temperature, a
      significant improvement of the GC response was achieved by cooling of the SPDE
      fiber during water extraction in comparison to an extraction keeping the fiber at
      room temperature. Evaluating the extraction cycles, for BTEX, the sensitivity was
      almost similar using 20, 40 and 60 extraction cycles. In contrast, the highest GC
      responses for n-aldehydes were achieved by the use of 60 extraction cycles.
      Optimizing the desorption parameters, best results were achieved using the
      smallest technical available desorption volume of 500 microL and the highest
      technical desorption flow rate of 50 microL/s. The method was applied to the
      analysis of melted snow samples taken from the Jungfraujoch, Switzerland (3580 m
      asl), revealing the presence of BTEX and aldehydes in snow.

PMID- 18054788
TI  - Multi-residue analysis of pharmaceutical compounds in aqueous samples.
AB  - Pharmaceutical compounds are nowadays an emerging group of organic pollutants in
      aquatic systems. Several methodologies have already been published to measure
      these pollutants in the environment, showing the difficulties to take into
      account the various compounds belonging to numerous therapeutical and chemical
      groups. In order to develop environmental monitoring, there is a need for a less
      costly and time-consuming multi-component procedure. The work presented here
      deals with the development of an extraction procedure which enables the
      measurement of a wide spectrum of pharmaceuticals at trace levels (ng 1(-1)) with
      quite simple equipment (i.e. GC-MS with single quadruple as analyzer). The
      analyzed compounds comprise anti-inflammatories, antidepressants and hypolipidic
      drugs. The reliability and sensitivity have been tested on 18 different compounds
      (7 basic compounds and 11 acidic drugs) extracted simultaneously and analyzed by
      GC-MS. The optimized procedure has been successfully applied to the analysis of
      wastewaters, surface waters and drinking waters from the following areas: first
      the Cortiou rocky inlet, in the Mediterranean Sea (South coast of France), highly
      impacted by the Marseilles wastewater treatment plant effluent and secondly the
      Herault watershed by studying drinking water, surface water and wastewater. In
      both cases, the level of pharmaceuticals was totally unknown. Results obtained
      have demonstrated the suitability of the method for multi-residue analysis of
      different types of water matrices.

PMID- 18054790
TI  - A deoxyribozyme with a novel guanine quartet-helix pseudoknot structure.
AB  - Here we report a deoxyribozyme with a unique structure that contains a two-tiered
      guanine quadruplex interlinked to a Watson-Crick duplex. Through in vitro
      selection, sequence mutation, and methylation interference, we show the presence
      of both the two-tiered guanine-quadruplex and two helical regions contained in
      the active structure of this self-phosphorylating deoxyribozyme. Interestingly,
      one GG element of the quadruplex is part of a hairpin loop within one of the
      identified helical regions. Circular dichroism analysis showed that antiparallel
      quadruplex formation was dependent on this helix. To our knowledge, this is the
      first report of a pseudoknot nucleic acid structure that involves a guanine
      quadruplex. Our findings indicate that guanine quadruplexes can be part of
      complex structural arrangements, increasing the likelihood of finding more
      complex guanine quadruplex arrangements in biological systems.

PMID- 18054789
TI  - Bloom's syndrome helicase and Mus81 are required to induce transient double
      strand DNA breaks in response to DNA replication stress.
AB  - Perturbed DNA replication either activates a cell cycle checkpoint, which halts
      DNA replication, or decreases the rate of DNA synthesis without activating a
      checkpoint. Here we report that at low doses, replication inhibitors did not
      activate a cell cycle checkpoint, but they did activate a process that required
      functional Bloom's syndrome-associated (BLM) helicase, Mus81 nuclease and ataxia
      telangiectasia mutated and Rad3-related (ATR) kinase to induce transient double
      stranded DNA breaks. The induction of transient DNA breaks was accompanied by
      dissociation of proliferating cell nuclear antigen (PCNA) and DNA polymerase
      alpha from replication forks. In cells with functional BLM, Mus81 and ATR, the
      transient breaks were promptly repaired and DNA continued to replicate at a slow
      pace in the presence of replication inhibitors. In cells that lacked BLM, Mus81,
      or ATR, transient breaks did not form, DNA replication did not resume, and
      exposure to low doses of replication inhibitors was toxic. These observations
      suggest that BLM helicase, ATR kinase, and Mus81 nuclease are required to convert
      perturbed replication forks to DNA breaks when cells encounter conditions that
      decelerate DNA replication, thereby leading to the rapid repair of those breaks
      and resumption of DNA replication without incurring DNA damage and without
      activating a cell cycle checkpoint.

PMID- 18054791
TI  - Mutations in the hydrophobic core of ubiquitin differentially affect its
      recognition by receptor proteins.
AB  - Ubiquitin (Ub) is one of the most highly conserved signaling proteins in
      eukaryotes. In carrying out its myriad functions, Ub conjugated to substrate
      proteins interacts with dozens of receptor proteins that link the Ub signal to
      various biological outcomes. Here we report mutations in conserved residues of
      Ub's hydrophobic core that have surprisingly potent and specific effects on
      molecular recognition. Mutant Ubs bind tightly to the Ub-associated domain of the
      receptor proteins Rad23 and hHR23A but fail to bind the Ub-interacting motif
      present in the receptors Rpn10 and S5a. Moreover, chains assembled on target
      substrates with mutant Ubs are unable to support substrate degradation by the
      proteasome in vitro or sustain viability of yeast cells. The mutations have
      relatively little effect on Ub's overall structure but reduce its rigidity and
      cause a slight displacement of the C-terminal beta-sheet, thereby compromising
      association with Ub-interacting motif but not with Ub-associated domains. These
      studies emphasize an unexpected role for Ub's core in molecular recognition and
      suggest that the diversity of protein-protein interactions in which Ub engages
      placed enormous constraints on its evolvability.

PMID- 18054792
TI  - Probing protein fold space with a simplified model.
AB  - We probe the stability and near-native energy landscape of protein fold space
      using powerful conformational sampling methods together with simple reduced
      models and statistical potentials. Fold space is represented by a set of 280
      protein domains spanning all topological classes and having a wide range of
      lengths (33-300 residues) amino acid composition and number of secondary
      structural elements. The degrees of freedom are taken as the loop torsion angles.
      This choice preserves the native secondary structure but allows the tertiary
      structure to change. The proteins are represented by three-point per residue,
      three-dimensional models with statistical potentials derived from a knowledge
      based study of known protein structures. When this space is sampled by a
      combination of parallel tempering and equi-energy Monte Carlo, we find that the
      three-point model captures the known stability of protein native structures with
      stable energy basins that are near-native (all alpha: 4.77 A, all beta: 2.93 A,
      alpha/beta: 3.09 A, alpha+beta: 4.89 A on average and within 6 A for 71.41%,
      92.85%, 94.29% and 64.28% for all-alpha, all-beta, alpha/beta and alpha+beta,
      classes, respectively). Denatured structures also occur and these have
      interesting structural properties that shed light on the different landscape
      characteristics of alpha and beta folds. We find that alpha/beta proteins with
      alternating alpha and beta segments (such as the beta-barrel) are more stable
      than proteins in other fold classes.

PMID- 18054793
TI  - Telomere ResQue and preservation--roles for the Werner syndrome protein and other
      RecQ helicases.
AB  - Werner syndrome is an autosomal recessive disorder resulting from loss of
      function of the RecQ helicase, WRN protein. WS patients prematurely develop
      numerous clinical symptoms and diseases associated with aging early in life and
      are predisposed to cancer. WRN protein and many other RecQ helicases in general,
      seem to function during DNA replication in the processing of stalled replication
      forks. Genetic, cellular and biochemical evidence support roles for WRN in proper
      replication and repair of telomeric DNA, and indicate that telomere dysfunction
      contributes to the WS disease pathology.

PMID- 18054794
TI  - Dyskeratosis Congenita: a historical perspective.
AB  - "Dyskeratosis Congenita (DC) also known as Zinsser-Engman-Cole syndrome is a rare
      multi-system bone marrow failure syndrome characterised by mucocutaneous
      abnormalities and an increased predisposition to cancer". This is a common
      definition of DC but how did this definition arise? The aim of this review is to
      follow the development of DC and associated diseases from its first reported
      description in the early 20th century to the current understanding of the genes
      involved and its pathophysiology in 2007 in a chronological order. Although this
      review is not intended to be an exhaustive citation of the literature available
      it does provide a summary of the key developments, citing particularly the
      earlier reports of each development.

PMID- 18054795
TI  - Common troublesome symptoms and their impact on quality of life in patients with
      myelodysplastic syndromes (MDS): results of a large internet-based survey.
AB  - Despite the clinical importance of health-related quality of life (QOL) in
      patients suffering from myelodysplastic syndromes (MDS), few data exist on the
      prevalence of key MDS-associated symptoms, or the correlation of those symptoms
      with specific disease features such as hemoglobin level. In order to better
      understand the burden of disease-associated symptoms in patients with MDS, we
      designed a 120-question Internet-based survey of QOL appropriate for patients
      with MDS, incorporating validated QOL measurement instruments and questions about
      specific therapies. The 359 survey respondents were typical of MDS patients in
      terms of demographics, blood counts, and disease subtype. Patients reported high
      levels of excessive fatigue and poor scores on QOL assessments such as the
      Functional Assessment of Cancer Therapy-Anemia (FACT-An) and the Brief Fatigue
      Inventory (BFI). Patients' debilitating fatigue correlated poorly with hemoglobin
      level, and fatigue was associated with significant impairment of both health
      related QOL and ability to work or participate in desired activities. Within the
      limitations of self-reported data, these results provide a benchmark for future
      interventions to improve QOL in patients with MDS.

PMID- 18054797
TI  - Role of cytomegalovirus in sensorineural hearing loss of children: a case-control
      study Tehran, Iran.
AB  - BACKGROUND: Congenital CMV is the most common cause of nonhereditary
      sensorineural hearing loss in children. More than 40% of deafness cases with an
      unknown cause are due to congenital CMV. When CMV infection is diagnosed in the
      first year of life, treatment with gancyclovir is recommended and is associated
      with diminished occurrence of SNHL. Previous studies in Tehran showed congenital
      CMV infection developed in 2.6% of neonates. OBJECTIVE: To determine the role of
      cytomegalovirus in sensorineural hearing loss in children by comparing the CMV
      antibodies quantitatively between SNHL and controls. METHODS AND MATERIALS: This
      case-control study was done in the ENT Department of Hazrat Rasoul Akram Hospital
      in Tehran (2002-2003). This study was carried out based on diagnostic parameters
      (AAO criteria) for SNHL and a healthy control. We compared the specific
      cytomegalovirus antibodies (IgM and IgG measured by ELISA method) in 95 blood
      samples of infants with SNHL (mean age=35+/-30 months) and 63 healthy matched
      infants (mean age=38.7+/-27.3 months) as controls. 59.6% of cases were male;
      40.4% were female. Acute and previous immunity to cytomegalovirus (IgM and IgG)
      was found in 34.7% and 72.6% of SNHL children, acute infection detected in 3.5%
      of controls, previous immunity (IgG) detected in 94.7% of them. Acute CMV
      infection was higher in the cases (P-value=0.000) but previous immunity (CMV-IgG)
      was higher in the controls (P-value=0.001). Mean age of cases with acute
      infection (CMV-IgM) was 40 months and for previous immunity (CMV-IgG) was 35
      months in SNHL cases and 40 months in controls, respectively. CONCLUSION:
      Cytomegalovirus is one of the most common infectious agents in SNHL children
      compared to the healthy children. Probably both congenital and acquired CMV can
      induce progressive hearing loss in our cases. We prefer at least in our country
      to consider seropositive (CMV-IgM) SNHL children (less than 1 year old) as
      congenital form. But we are not able to differentiate the congenital from the
      acquired infection in seropositive (CMV-IgM) SNHL children after first year of
      life. It should be subjected to randomized controlled trial for treatment of
      acquired type of CMV infection in SNHL children with ganciclovir.

PMID- 18054796
TI  - Feedforward and feedback inhibition in neostriatal GABAergic spiny neurons.
AB  - There are two distinct inhibitory GABAergic circuits in the neostriatum. The
      feedforward circuit consists of a relatively small population of GABAergic
      interneurons that receives excitatory input from the neocortex and exerts
      monosynaptic inhibition onto striatal spiny projection neurons. The feedback
      circuit comprises the numerous spiny projection neurons and their
      interconnections via local axon collaterals. This network has long been assumed
      to provide the majority of striatal GABAergic inhibition and to sharpen and shape
      striatal output through lateral inhibition, producing increased activity in the
      most strongly excited spiny cells at the expense of their less strongly excited
      neighbors. Recent results, mostly from recording experiments of synaptically
      connected pairs of neurons, have revealed that the two GABAergic circuits differ
      markedly in terms of the total number of synapses made by each, the strength of
      the postsynaptic response detected at the soma, the extent of presynaptic
      convergence and divergence and the net effect of the activation of each circuit
      on the postsynaptic activity of the spiny neuron. These data have revealed that
      the feedforward inhibition is powerful and widespread, with spiking in a single
      interneuron being capable of significantly delaying or even blocking the
      generation of spikes in a large number of postsynaptic spiny neurons. In
      contrast, the postsynaptic effects of spiking in a single presynaptic spiny
      neuron on postsynaptic spiny neurons are weak when measured at the soma, and
      unable to significantly affect spike timing or generation. Further, reciprocity
      of synaptic connections between spiny neurons is only rarely observed. These
      results suggest that the bulk of the fast inhibition that has the strongest
      effects on spiny neuron spike timing comes from the feedforward interneuronal
      system whereas the axon collateral feedback system acts principally at the
      dendrites to control local excitability as well as the overall level of activity
      of the spiny neuron.

PMID- 18054798
TI  - Defective apoptotic cell clearance in asthma and COPD--a new drug target for
      statins?
AB  - Asthma and chronic obstructive pulmonary disease represent increasingly common
      respiratory conditions with a clear unmet need for more effective and safer
      therapy. Airway inflammation is key to both asthma pathogenesis and exacerbations
      of symptoms in chronic obstructive pulmonary disease. Several lines of evidence
      are now emerging implicating the increased persistence of apoptotic cells in
      patients with chronic inflammatory lung diseases and that this is largely due to
      a combination of inhibition of, or defects in, the apoptotic process and/or
      impaired apoptotic cell removal mechanisms.

PMID- 18054799
TI  - HIV-1 protease inhibitors: effects on HIV-2 replication and resistance.
AB  - Novel antiretroviral drugs include protease (PR) inhibitors (e.g. atazanavir,
      tipranavir and darunavir) that block HIV-1 maturation and show remarkable
      antiviral potency on drug-resistant isolates. However, the strains used as
      prototypes in the design of the novel drugs belong to a specific clade (i.e. HIV
      1 group M subtype B), which is the most prevalent in developed countries. At the
      same time, there is an increasing concern about the expansion of other HIV-1
      clades as well as other related retroviruses, such as HIV-2. The HIV-2 PR is
      weakly inhibited by some PR inhibitors (e.g. amprenavir), and little is known of
      the mutational pathways leading to drug resistance in this virus. The design of
      specific PR inhibitors targeting HIV-2, or potent drugs showing broad specificity
      on HIV-1 and HIV-2 clades, remains a major challenge for the future.

PMID- 18054800
TI  - CDK inhibitors in cancer therapy: what is next?
AB  - The pursuit for drugs that inhibit cyclin-dependent kinases (CDKs) has been an
      intense area of research for more than 15 years. The first-generation inhibitors,
      Flavopiridol and CY-202, are in late-stage clinical trials, but so far have
      demonstrated only modest activity. Several second-generation inhibitors are now
      in clinical trials. Future approaches to determine clinical benefit need to
      incorporate both the lessons learned from these early compounds and information
      recently obtained from the genetic analysis of CDKs in preclinical models. Here
      we discuss key concepts that should be considered when validating the clinical
      utility of CDK inhibitors in cancer therapy.

PMID- 18054801
TI  - Calcium dynamics: analyzing the Ca2+ regulatory network in intact cells.
AB  - Calcium signaling is critical for all cells. As a free ion (Ca(2+)), calcium
      links many physiological stimuli to their intracellular effectors by interacting
      with binding proteins whose occupancy determines the cellular effect of
      stimulation. Because binding site occupancy depends on the history of Ca(2+)
      concentration ([Ca(2+)]), Ca(2+) dynamics are critical. Calcium dynamics depend
      on the functional interplay between Ca(2+) transport and buffering systems whose
      activities depend nonlinearly on [Ca(2+)]. Thus, understanding Ca(2+) dynamics
      requires detailed information about these Ca(2+) handling systems and their
      regulation in intact cells. However, effective methods for measuring and
      characterizing intracellular Ca(2+) handling have not been available until
      recently. Using concepts relating voltage-gated ion-channel activity to membrane
      potential dynamics, we developed such methods to analyze Ca(2+) fluxes in intact
      cells. Here we describe this approach and applications to understanding
      depolarization-induced Ca(2+) responses in sympathetic neurons.

PMID- 18054802
TI  - Water movements in the brain: role of aquaporins.
AB  - About 80% of the brain is water. This review discusses the importance of the
      three brain water-channel proteins (AQP1, AQP4, AQP9) in brain physiology. AQP1
      is expressed in the choroid plexus and participates in forming cerebrospinal
      fluid. AQP4, found in astrocyte foot processes, glia limitans and ependyma,
      facilitates water movement into and out of the brain, accelerates astrocyte
      migration and alters neuronal activity. Recently, AQP4 autoantibodies were
      discovered in patients with neuromyelitis optica, a demyelinating disease, and
      are now being used to diagnose this condition. AQP9 is present in some glia and
      neurons, but its function is unclear. Finally, we discuss how the discovery of
      AQP activators and inhibitors will be the next major step in this field.

PMID- 18054803
TI  - Melanopsin: an exciting photopigment.
AB  - The discovery that mice lacking rods and cones are capable of regulating their
      circadian rhythms by light provided the conceptual framework for the discovery of
      an entirely new photoreceptor system within the mammalian eye. We now know that a
      small subset of retinal ganglion cells are directly photosensitive and utilize an
      opsin/vitamin A-based photopigment called melanopsin maximally sensitive in the
      blue part of the spectrum. We also know that these photosensitive retinal
      ganglion cells mediate a broad range of physiological responses to light, ranging
      from the regulation of circadian rhythms to pupil constriction. Most recently, it
      has become clear that the melanopsins are only distantly related to visual
      pigments and in terms of their biochemistry share more in common with
      invertebrate photopigments. Here we outline the discovery of this remarkable new
      photoreceptor system, review the structure of melanopsin and conclude with a
      working model of melanopsin phototransduction.

PMID- 18054804
TI  - Alarm substance induced behavioral responses in zebrafish (Danio rerio).
AB  - Zebrafish (zebra danio) are becoming increasingly popular in behavioral
      neuroscience and behavior genetics. This small vertebrate may be utilized in
      modeling human brain disorders. One of the major neuropsychiatric conditions
      still not well understood is abnormally increased fear and anxiety. Zebrafish may
      be an appropriate organism with which these human diseases can be modeled and
      their biological mechanisms investigated. Predator induced anxiety paradigms have
      been suggested as useful methods in translational research. Shoaling fish, such
      as zebrafish, are known to respond to alarm substances with antipredatory or
      alarm reactions. However, these responses are not well characterized in
      zebrafish. In the current paper, we investigate the behavioral responses of
      zebrafish elicited by its alarm substance. Using observation-based as well as
      video-tracking aided behavior quantification methods we demonstrate significant
      alarm substance-induced behavioral changes that are independent of the presence
      of a predatory fish stimulus. The results suggest that, once refined, the use of
      alarm substance with zebrafish will allow the development of high throughput
      behavioral paradigms for drug and mutation screening aimed at the analysis of the
      biological mechanisms of fear in vertebrates.

PMID- 18054805
TI  - The microinjection of AMPA receptor antagonist into the accumbens shell, but not
      into the accumbens core, induces anxiolysis in an animal model of anxiety.
AB  - This study investigated the effect of the AMPA receptor antagonist 6,7
      dinitroquinoxaline-2,3-dione (DNQX) microinjected into the core and shell sub
      regions of the accumbens nucleus (Acb), on the level of fear/anxiety and
      emotional learning, in female rats submitted to the elevated plus-maze (EPM), an
      animal model of anxiety. Bilateral microinjections of DNQX (330 and 660 ng) into
      the Acb shell (AP, +1.08 to +2.16) induced an anxiolytic-like effect in relation
      to rats microinjected with vehicle, since there was an increased percentage of
      entries in the open arms of the maze. The 660 ng DNQX microinjection into the Acb
      shell also increased the percentage of entries into the open arms in relation to
      660 ng DNQX microinjection into the Acb core. Prior DNQX microinjections in both
      core and shell sub-regions of the Acb failed to impair the emotional learning,
      since the animals exhibited an increase of the open arm avoidance on EPM Trial 2
      in relation to EPM trial 1. DNQX microinjections into both sub-regions of the Acb
      did not change the number of entries into the enclosed arms, either in the EPM
      Trial 1 or in the EPM Trial 2, which indicates an absence of drug-induced
      locomotor impairment. Similarly, DNQX microinjections into both sub-regions of
      the Acb failed to alter the total arm entries, rearing, grooming and head-dipping
      frequency. The anxiolytic-like effect induced by DNQX suggests that the AMPA
      receptor in the Acb shell, but not in the Acb core, may underlie anxiety
      regulation in the EPM.

PMID- 18054806
TI  - Effects of naphthalene on gene transcription in Calanus finmarchicus (Crustacea:
      Copepoda).
AB  - The planktonic copepod Calanus finmarchicus is a key species in the Northern
      Atlantic food web; an oceanic area with extensive oil production. Naphthalene is
      one of the major constituents of produced water and water soluble fractions of
      petrogenic oils. This study investigates the effects on gene transcription of a
      short term exposure to naphthalene at levels well below LC(50) concentrations.
      This was done in order to establish a molecular basis of naphthalene toxicity in
      a species which has previously been subject only to very limited studies at the
      molecular level. Naphthalene exposure to C. finmarchicus was found to cause
      glutathione S-transferase (GST) induction, indicating lipid peroxidation as the
      major mode of naphthalene toxicity. There is no clear evidence that the putative
      cytochrome P450 enzymes CYP1A2 and CYP330A1 mRNAs are parts of a detoxification
      enzyme system. Instead, an observed decrease in CYP330A1 mRNA levels at the
      highest naphthalene exposure concentration may indicate an effect on
      ecdysteroidogenesis. Only the lowest naphthalene concentration lead to increased
      mRNA levels of antioxidants SOD and CAT, indicating no clear evidence for general
      cellular oxidative stress following exposure. Small and insignificant changes in
      the HSP-70, HSP-90 and ubiquitin mRNA levels indicate a small degree of protein
      damage owing to naphthalene exposure. The established culture of C. finmarchicus
      at the SINTEF/NTNU Sealab, and the use of gene transcription analyses provide
      excellent tools for improving the understanding of biochemical mechanisms
      involved in the defense against environmental impacts and the molecular modes of
      toxicity in this species.

PMID- 18054807
TI  - Prevalence and significance of Brugada-type ECG in 12,012 apparently healthy
      European subjects.
AB  - BACKGROUND: The prevalence of the Brugada-type ECG and its natural history are
      still unclear. The recently proposed diagnostic criteria have not been
      systematically applied in a European general population. METHODS: We
      retrospectively analyzed ECGs and clinical data of 12,012 apparently healthy
      individuals who had undergone medical examination for occupational reasons. We
      sought follow-up information on the subjects with at least one ECG fulfilling the
      criteria for the Brugada pattern. RESULTS: A Brugada-type ECG was found in 23
      subjects (0.19%; 95% confidence interval 0.12-0.27%) on the first ECG recorded in
      that subject. In a further 8 cases, the Brugada pattern was present in a
      subsequent ECG, so that it was present at some time in 31 subjects (0.26%, 95%
      confidence interval 0.18-0.37%), all male. Only 2 patients displayed the
      classical type 1 Brugada ECG pattern. In 29 patients (94%), clinical information
      was available subsequent to the first Brugada pattern ECG recorded. The mean
      follow-up was 10.1+/-5.5 years. A sudden death occurred in a 27-year-old man with
      Brugada type 2 ECG pattern. No sudden death or symptomatic ventricular arrhythmia
      occurred among the other 28 patients. The annual rate of sudden death associated
      with Brugada ECG pattern was 0.3% per patient-year of follow-up. CONCLUSION: The
      Brugada-type ECG pattern, as currently defined, is uncommon in a young healthy
      male European population and confers a moderately elevated risk of sudden death.
      Our findings underscore the need to study risk predictors in asymptomatic
      patients with a Brugada-type ECG.

PMID- 18054808
TI  - Lack of decrease in plasma N-terminal pro-brain natriuretic peptide identifies
      acute heart failure patients with very poor outcome.
AB  - BACKGROUND: Optimal risk stratification in heart failure patients surviving an
      episode of acute decompensation has not yet been established. We investigated
      whether a lack of significant decrease in plasma levels of N-terminal pro-brain
      natriuretic peptide (NT-proBNP) during hospital stay can identify patients at
      high risk of poor outcome. METHODS: We studied 103 consecutive patients with
      acute heart failure (86 men, age: 64 + or - 13 years, LVEF: 28 + or - 8%). The
      primary end-point was all-cause mortality at 1-year follow-up. RESULTS: Median
      plasma NT-proBNP on admission was 6116 pg/mL (upper/lower quartiles: 3575,
      10,958) vs. 2930 pg/mL (1674, 5794) after clinical stabilization (7 + or - 3 days
      after admission). During the 1-year follow-up 29 (28%) patients died. A decrease
      in plasma NT-proBNP during clinical recovery (expressed as percentage of NT
      proBNP on admission) predicted favorable outcome in the single predictor analysis
      (p<0.001) and multivariable analyses (p<0.001). Receiver operating characteristic
      curve analysis revealed that 65% was the cut-off value for NT-proBNP decrease
      having best prognostic accuracy for predicting death (sensitivity 90%,
      specificity 37%, AUC=0.65, 95% CI: 0.54-0.74). Kaplan-Meier analysis showed that
      12-month survival was 92% (95% CI: 81-100%) for patients with > pr = 65% NT
      proBNP decrease vs 66% (95% CI: 56-76%) in those with <65% NT-proBNP decrease
      (p=0.02). CONCLUSIONS: The magnitude of plasma NT-proBNP decrease in patients
      with acute heart failure is helpful in discrimination of patients at high risk of
      death. Plasma NT-proBNP level monitoring is important for risk stratification in
      this group of patients.

PMID- 18054809
TI  - The 12-week progressive quadriceps resistance training improves muscle strength,
      exercise capacity and quality of life in patients with stable chronic heart
      failure.
AB  - BACKGROUND: Abnormalities in the skeletal musculature underlie exercise
      intolerance in chronic heart failure (CHF). We investigated, whether in CHF
      selective resistance training without accompanying aerobic regime favourably
      affects muscle strength, muscle mass and improves exercise capacity. METHODS: Ten
      patients with stable ischaemic CHF in NYHA class III (9 men, age: 70+/-6 years
      [mean+/-SD], left ventricular ejection fraction: 30+/-5%, peak oxygen consumption
      [peak VO(2)]: 12.4+/-3.0 mL/min/kg) underwent the rehabilitation programme which
      consisted of a 12-week training phase (progressive resistance exercises
      restricted to the quadriceps muscles) followed by a 12-week detraining phase.
      RESULTS: All subjects completed a training phase of the programme with no adverse
      events. Resistance training markedly increased quadriceps strength (right leg:
      260+/-34 vs. 352+/-28 N, left leg: 264+/-38 vs. 342+/-30 N, both p<0.01 - all
      comparisons: baseline vs. after training), but did not affect lean tissue mass of
      lower extremities (both p>0.2). It was accompanied by an improvement in clinical
      status (all NYHA III vs. all NYHA II, p<0.01), quality of life (Minnesota
      questionnaire: 44+/-15 vs. 33+/-18 points, p<0.05), exercise capacity assessed
      using a distance during 6-minute walk test (6MWT: 362+/-83 vs. 455+/-71 m,
      p<0.01), but not peak VO(2) (p>0.2). Plasma NT-proBNP remained unchanged during
      the training. At the end of detraining phase, only a partial improvement in
      quadriceps strength (p<0.05), a 6MWT distance (p<0.05) and NYHA class (p=0.07 vs.
      baseline) persisted. CONCLUSIONS: Applied resistance quadriceps training is safe
      in patients with CHF. It increases muscle strength, improves clinical status,
      exercise capacity, and quality of life.

PMID- 18054810
TI  - Immobilization in alginate as a technique for the preservation of Bacillus
      thuringiensis var. israelensis for long-term preservation.
AB  - Technique for immobilization using sodium alginate as the matrix to preserve
      Bacillus thuringiensis var. israelensis isolates for long time storage was
      developed. Two strains of B. thuringiensis var. israelensis viz., VCRC B-17 and
      WHO standard strain IPS-82 were immobilized in alginate matrix and preserved at 4
      degrees C and when tested both were found to have maintained excellent viability
      and mosquito larvicidal activity for 10 years. Mosquito larvicidal activity of B
      17 and IPS-82 alginate beads, in term of LC(50) values before storage was 72.07
      ng/ml and 47.07 ng/ml, respectively and after storage at 4 degrees C for a period
      of 1 to 10 years the values ranged from 69.88 to 73.86 ng/ml with a mean of 72.38
      ng/ml and 45.32 to 48.60 ng/ml with a mean of 47.49 ng/ml, respectively.
      Similarly spore count of the beads of the respective strains was 4.37 x 10(8) and
      3.33 x 10(10) CFU/mg before storage. After storage at 4 degrees C for a period of
      1 to 10 years the counts of the beads of the respective strains ranged from 4.23
      x 10(8) to 4.83 x 10(8) CFU/mg (mean of 4.49 x 10(8) CFU/mg) and 3.2 x 10(10) to
      3.87 x 10(10) CFU/mg (mean of 3.54 x 10(10) CFU/mg). The alginate matrix
      immobilization technique has many advantages over free cells are that they
      enhance the stability of both spores and toxin against several physicochemical
      conditions and confer reduced susceptibility to contamination.

PMID- 18054811
TI  - Identification and characterization of a late AH1N2 human reassortant in France
      during the 2002-2003 influenza season.
AB  - We have previously shown a clear differential genetic evolution of the
      hemagglutinin (HA) of human AH1N1 and AH1N2 viruses, isolated in southern France
      between 2001 and 2004. However, our analysis revealed that one single AH1N2
      isolate, detected in 2003 (A/Lyon/0838/2003), had its HA clustering within the
      HAs of the AH1N1 subtypes. To determine if this virus was a new reassortant, the
      nucleotide sequences of its eight RNA gene segments were compared with those of
      five representative strains of the AH1N1, AH1N2 and AH3N2 viruses, isolated
      during the same time-period. According to the sequences obtained, the
      neuraminidase (NA) gene segment of the A/Lyon/0838/2003 (H1N2) virus was
      genetically closely related to those of the AH1N2 viruses, whereas the six
      internal genes appeared to be clustering with those of the AH1N1 viruses. This
      suggested that the A/Lyon/0838/2003 (H1N2) virus was the result of a second
      reassortment event that had occurred during the winter of 2002-2003; the N2 gene
      segment of an AH1N2 virus being introduced into an AH1N1 genetic background.
      Subsequently, we analysed the extremities of each gene segment of the viruses
      from the different subtypes, and experimentally reproduced, in vitro, AH1N2
      reassortant viruses through co-infection of Madin-Darby canine kidney (MDCK)
      cells with both AH1N1 and AH1N2 viruses, isolated in the 2002-2003 influenza
      season. While the comparison of the AH1N1 and the AH1N2 gene segment extremities
      revealed no major differences, we successfully reproduced an AH1N2 reassortant
      virus similar to the A/Lyon/0838/2003 (H1N2) virus. This result provided an
      experimental evidence of the compatibility between their respective surface H1
      and N2 glycoproteins, and suggests that similar events may occur silently amongst
      human subtypes.

PMID- 18054812
TI  - A novel IRQ ligand-modified nano-carrier targeted to a unique pathway of caveolar
      endocytic pathway.
AB  - In the present study, the cellular uptake and subsequent intracellular
      trafficking of liposomes was investigated, in which a novel peptide (IRQ),
      identified with in vivo phage display, was modified on the surface. Since the
      novel peptide IRQRRRR is rich in arginine, the cellular uptake mechanism was
      compared with octaarginine (R8)-modified liposomes, which are known to be taken
      up by cells via macropinocytosis. The uptake mechanism and intracellular
      trafficking of peptide-modified liposomes was determined by confocal laser
      scanning microscopy and flow cytometry analysis. Modification of the liposomal
      surface with the IRQ peptide (IRQ-Lip), induced internalization via a novel
      pathway-caveolar endocytosis-in parallel with clathrin-mediated endocytosis.
      Furthermore, the IRQ peptide stimulated escape from endocytic vesicles, leading
      to efficient gene silencing. When siRNA was condensed and encapsulated in an IRQ
      modified multifunctional envelope-type nano-device (IRQ-MEND), transgene
      expression was reduced 52% with the fusogenic lipid, DOPE/CHEMS. This result
      shows that the novel IRQ can be utilized for cytoplasmic delivery of
      macromolecules. Moreover, the IRQ has the potential to be useful for delivery
      therapeutic agents to parenchymal cells via caveolar endocytosis, as this uptake
      pathway also plays an important role in transcytosis.

PMID- 18054813
TI  - Trinucleotide repeats are prevalent among cancer-related genes.
AB  - Trinucleotide repeats (TNRs) have been primarily connected to neurologic and
      neuromuscular diseases, with few specific TNRs linked with various tumors. Here
      we conduct a genome-wide analysis and show that TNRs are five times more
      prevalent in cancer-related human genes. Interestingly, we also find that cancer
      related genes are significantly longer than other genes. Our results suggest that
      genes containing TNRs are more prone to mutagenesis. The database of TNR genes
      can be used as a list of candidate cancer-related genes.

PMID- 18054815
TI  - Adrenomedullin is increased by pulsatile shear stress on the vascular endothelium
      via periodic acceleration (pGz).
AB  - Periodic acceleration (pGz) is produced by a platform which moves the supine body
      repetitively in a headward to footward direction. The imparted motion produces
      pulsatile shear stress on the vascular endothelium. Pulsatile shear stress on the
      vascular endothelium has been shown to elicit production of a host of
      cardioprotective, cytoprotective mediators. The purpose of this study was to
      ascertain if pGz also enhances production of adrenomedullin (AM) in normal
      healthy swine. Twelve pigs (weight range 20-30 kg) were anesthetized, intubated
      and placed on conventional mechanical ventilation. All animals were secured to
      the motion platform. In one group (pGz) (n=7) was activated for 1h, and monitored
      for an additional 3h. A control group (CONT) (n=5) served as time control.
      Arterial blood gases, hemodynamic measurements, and serum for AM, interleukin 4,
      6 and thromboxane B(2) (TBXB2) were measured at baseline, immediately after pGz,
      and 3h after pGz had been discontinued. There was no significant change from
      baseline value in IL-4, IL-6 or TBXB2. Mean arterial blood pressure decreased in
      pGz-treated animals from 115+/-10 at baseline to 90+/-8 after 60 min of pGz
      (p<0.01). AM levels increase from 776+/-176 pg/ml baseline to 1160+/-68 pg/ml
      immediately after pGz, and remained elevated to 1584+/-160 pg/ml, 3h after pGz
      (p<0.01 vs. BL). This is the first report of AM-enhanced production using a non
      invasive method of increasing pulsatile shear stress on the vascular endothelium.
      pGz increases production of AM in normal healthy swine. These changes are
      independent of IL-4, IL-6 or TBXB2 production.

PMID- 18054814
TI  - A polymorphism in the angiogenesis inhibitor, endostatin, in lung cancer
      susceptibility.

PMID- 18054816
TI  - Assessment of methodological quality and sources of variation in the magnitude of
      vaccine efficacy: a systematic review of studies from 1960 to 2005 reporting
      immunization with Moraxella bovis vaccines in young cattle.
AB  - A review was conducted of all identified literature evaluating Moraxella bovis
      vaccines efficacy in preventing pinkeye in beef calves. From 292 publications
      identified by the search, data on 123 unique vaccine-to-control comparisons were
      extracted from 38 studies published in English from 1960 to 2005. Descriptive
      analysis was performed and an analysis of sources of variation evaluated. Use of
      methods to control bias such as randomization and blinding were associated with
      decreased vaccine efficacy. Only 15 trials reported using randomization and
      blinding. The authors conclude that when designing and reporting veterinary
      vaccination studies, researchers must include methodological quality information
      necessary to judge the evidence produced from the study.

PMID- 18054818
TI  - Factors associated with pneumococcal immunisation among hospitalised elderly
      persons: a survey of patient's perception, attitude, and knowledge.
AB  - AIM: To investigate attitudes, perceptions and knowledge of elderly hospital
      patients in regard to vaccination in general and pneumococcal vaccination in
      particular. SETTING: A hospital-based patient survey in Sydney, Australia.
      PARTICIPANTS: Patients aged 60 years and older who are admitted to selected wards
      in an 800-bed tertiary referral hospital in Sydney, Australia. METHODS: A face-to
      face interview administered to 200 inpatients. RESULTS: Approximately half (49%)
      of the patients had a positive attitude to vaccination whereas 59% had less
      positive perception. There were 35% of the patients who were unvaccinated against
      influenza and pneumococcal disease. Positive perception (OR 2.9, 95% C.I.=1.3
      6.5) and attitude (OR 4.4, 95% C.I.=2.0-9.4) significantly predicted vaccination
      with both vaccines. Similarly the odds of receiving pneumococcal vaccination for
      those who had a more positive attitude and more correct knowledge were
      significant (OR=2.3, 95% C.I.=1.0-5.4; OR=2.7, 95% C.I.=1.1-6.8). We explored
      reasons for non-vaccination. Physician recommendation was listed as an important
      factor by patients. CONCLUSIONS: Positive perception and attitude towards
      vaccination are significant factors associated with immunisation status. For the
      pneumococcal vaccination, having influenza vaccination is related to pneumococcal
      vaccination.

PMID- 18054817
TI  - Markedly enhanced immunogenicity of a Pfs25 DNA-based malaria transmission
      blocking vaccine by in vivo electroporation.
AB  - Pfs25 is a promising target antigen for the development of a malaria transmission
      blocking vaccine and prior research has demonstrated induction of high and
      functionally effective antibodies in mice with IM injection of Pfs25 encoding DNA
      plasmid. Likewise, Pfs25 DNA vaccine was immunogenic in rhesus macaques but
      required a protein boost to elicit significant transmission-blocking antibodies.
      The translation of these encouraging findings to human clinical trials has been
      impeded largely by the relatively poor immunogenicity of DNA plasmids in larger
      animals. In vivo electroporation (EP) has revealed significant enhancement of the
      potency of DNA plasmids. The results reported here compared the immunogenicity
      and functional transmission-blocking effects of immunization with DNA plasmid (25
      microg) by the traditional IM route compared to coupling the IM injection (0.25,
      2.5 and 25 microg doses) with in vivo EP. Significantly, a 0.25 microg dose of
      DNA plasmid, when administered with EP, induced antibody titers (1:160,000) and
      functional transmission-blocking effects that were equivalent to those achieved
      by a one hundred fold higher (25 microg) dose of DNA plasmid given without EP. At
      a 25.0 microg DNA dose with or without EP there was sufficient antigenic
      stimulation to result in effective antibody titers; however EP method yielded
      antibody titer of 1:1,280,000 as compared to only 1:160,000 titer without EP.
      This observed two log reduction in the amount of DNA plasmid required to induce
      significant transmission-blocking effects makes a compelling argument in favor of
      further evaluation of DNA vaccines by in vivo EP method in larger animals.
      Further experiments in non-human primates and eventually in phase I human trials
      will determine if the use of EP will induce effective and sustained malaria
      transmission-blocking effects at acceptable doses of plasmid DNA.

PMID- 18054819
TI  - [Place of the precocious surgical treatment in facial hemangioma].
AB  - Infantile cutaneous hemangioma is a benign vascular tumour present at 10% of the
      infants. It forms part of the group of the vascular tumours in the classification
      of international society for vascular anomalies (ISSVA). Usual surgical attitude
      is abstention and surgery is proposed only in order to treat sequelae. But some
      particular situations require early surgery to avoid functional impairment,
      deformation or growth delay due to the lesion's development. Using our
      observations, we recall the epidemiology, the physiopathology, the clinical
      aspects, the particularities of the facial localizations and their treatments. In
      these localizations the time intervenes like a fourth dimension that is going to
      modify, to improve or to aggravate the prognosis. Treatment requires a strategy
      and precocious surgery. We insist on the fact that the dogma of the therapeutic
      abstention remained true for a majority of children with small size hemangioma
      and that a precocious surgery must be proposed for some localizations in the
      face.

PMID- 18054820
TI  - [Lipomodelling for correction of breast conservative treatment sequelae.
      Medicolegal aspects. Expert opinion on five problematic clinical cases].
AB  - In our unit, breast cancer patients suffering mild sequelae of conservative
      cancer treatment receive fat transfer (lipomodelling), following a precise
      protocol, based on mammographic and ultrasound examinations and MRI. Available
      data do not seem to indicate any deleterious impact on patient outcome, notably
      in view of radiological images, but recurrence (or rather occurrence of new
      ipsilateral or contralateral cancer) is frequent. The correlation between new or
      recurrent breast cancer and lipomodelling is high; misinterpretations are
      possible and frequently arise. The present paper is a description of five complex
      clinical cases and a discussion of the medicolegal issues that may possibly
      arise; it also provides tentative expert evaluation of the cases. Clinical
      findings are reported and analyzed. The second step is a discussion of the
      radiological impact of lipomodelling, and of the problems caused by the transfer
      of potentially malignant cells when no preoperative diagnosis of recurrence is
      made; the morphological and esthetic benefits of the method are described, as
      well as the potential beneficial impact of fat transfer, notably associated with
      lower breast density and injections of fat stem cells. Our conclusion is that
      specialized radiologists, as well as plastic surgery and oncology experts should
      address the question of fat transfer in operated breast cancer patients and give
      their reasoned opinion about potentially litigious cases. This would help
      minimize or solve the conflicts between patients, doctors and experts.
      Establishing common ground between the different stakeholders would allow the
      development of the technique, as lipomodelling is, according to our experience, a
      tremendous advance in the treatment of sequelae from conservative breast cancer
      surgery.

PMID- 18054821
TI  - An evaluation of therapeutic and reactivating effects of newly developed oximes
      (K156, K203) and commonly used oximes (obidoxime, trimedoxime, HI-6) in tabun
      poisoned rats and mice.
AB  - The potency of newly developed monoxime bispyridinium compounds (K156, K203) in
      reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced
      lethal toxic effects was compared with commonly used oximes (obidoxime,
      trimedoxime, the oxime HI-6) using in vivo methods. Studies determining
      percentage of reactivation of tabun-inhibited blood and tissue
      acetylcholinesterase in poisoned rats showed that the reactivating efficacy of
      newly developed oxime K203 is comparable with obidoxime and trimedoxime in blood
      and higher than the reactivating potency of trimedoxime and obidoxime in
      diaphragm and brain, where the difference in reactivating efficacy of obidoxime,
      trimedoxime and K203 is significant. On the other hand, the potency of newly
      developed K156 to reactivate tabun-inhibited acetylcholinesterase is comparable
      with obidoxime or trimedoxime in diaphragm and brain. It is significantly lower
      than the reactivating efficacy of trimedoxime and obidoxime in blood. Moreover,
      both newly developed oximes were found to be relatively efficacious in the
      reduction of lethal toxic effects in tabun-poisoned mice. Especially, the oxime
      K203 is able to decrease the acute toxicity of tabun nearly two times. The
      therapeutic efficacy of K156 and K203 corresponds to their potency to reactivate
      tabun-inhibited acetylcholinesterase, especially in diaphragm and brain. In
      contrast to obidoxime and trimedoxime, the oxime HI-6 is not effective in
      reactivation of tabun-inhibited acetycholinesterase and in reducing tabun
      lethality. While the oxime K156 does not improve the reactivating and therapeutic
      effectiveness of currently available obidoxime and trimedoxime, the newly
      developed oxime K203 is markedly more effective in reactivation of tabun
      inhibited acetylcholinesterase in rats, especially in brain, and in reducing
      lethal toxic effects of tabun in mice and, therefore, it is suitable for the
      replacement of commonly used oximes for the antidotal treatment of acute tabun
      poisoning.

PMID- 18054822
TI  - Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands
      inhibit growth of UACC903 and MCF7 human cancer cell lines.
AB  - The development of peroxisome proliferator-activated receptor-beta/delta
      (PPARbeta/delta) ligands for the treatment of diseases including metabolic
      syndrome, diabetes and obesity has been hampered due to contradictory findings on
      their potential safety. For example, while some reports show that ligand
      activation of PPARbeta/delta promotes the induction of terminal differentiation
      and inhibition of cell growth, other reports suggest that PPARbeta/delta ligands
      potentiate tumorigenesis by increasing cell proliferation. Some of the
      contradictory findings could be due in part to differences in the ligand
      examined, the presence or absence of serum in cell cultures, differences in cell
      lines or differences in the method used to quantify cell growth. For these
      reasons, this study examined the effect of ligand activation of PPARbeta/delta on
      cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903
      (melanoma) in the presence or absence of serum using two highly specific
      PPARbeta/delta ligands, GW0742 or GW501516. Culturing cells in the presence of
      either GW0742 or GW501516 caused upregulation of the known PPARbeta/delta target
      gene angiopoietin-like protein 4 (ANGPTL4). Inhibition of cell growth was
      observed in both cell lines cultured in the presence of either GW0742 or
      GW501516, and the presence or absence of serum had little influence on this
      inhibition. Results from the present studies demonstrate that ligand activation
      of PPARbeta/delta inhibits the growth of both MCF7 and UACC903 cell lines and
      provide further evidence that PPARbeta/delta ligands are not mitogenic in human
      cancer cell lines.

PMID- 18054823
TI  - Inhibition, reactivation and aging kinetics of highly toxic organophosphorus
      compounds: pig versus minipig acetylcholinesterase.
AB  - Organophosphorus compound-based (OP) chemical warfare agents (nerve agents)
      represent a continuing threat to military forces and the civilian population. OPs
      act primarily by inhibiting acetylcholinesterase (AChE), the standard treatment
      for which includes AChE reactivators (oximes) in combination with antimuscarinic
      drugs. In the last decades, the efficacy of oximes has been investigated mostly
      in small animal models. In order to increase the predictive value of animal
      studies it is desirable to measure numerous physiological and biochemical
      parameters. This is difficult in small animals. Large animal models fulfil these
      requirements and swine are increasingly being used in toxicology studies. Swine
      breeds generally show considerable variability in different characteristics which
      may be minimised by the use of specially bred minipigs which have a known genetic
      background and health status. A comparative study was, therefore, initiated to
      investigate the kinetic properties of the White Landrace pig and Gottingen
      minipig AChE in respect of inhibition by the pesticide paraoxon; the nerve agents
      cyclosarin, VX and VR; the reactivation of inhibited AChE by oximes (obidoxime,
      pralidoxime and HI 6); and the aging and spontaneous reactivation of inhibited
      AChE. The determination of the respective kinetic constants found similarities
      between pig and minipig AChE which showed marked differences in comparison with
      human AChE values. This has to be considered in designing meaningful models for
      the investigation of oxime efficacy in pig or minipig experiments. The generated
      data indicate comparable kinetic properties of pig and minipig AChE and may
      provide a kinetic basis for extrapolation of data from pig studies to humans.

PMID- 18054825
TI  - Toxicities associated with the administration of sorafenib, sunitinib, and
      temsirolimus and their management in patients with metastatic renal cell
      carcinoma.
AB  - OBJECTIVE: To provide a systematic review of the side effects associated with
      sorafenib, sunitinib, and temsirolimus and to provide an outline of possible
      preventive or therapeutic measures. METHODS: We performed a PubMed-based
      systematic review of side effects associated with the three agents and relied on
      product monographs and prescribing information to provide an outline of
      treatments aimed at reducing these toxicities. RESULTS: Side effects range from
      <1% to 72%. Grade 3/4 side effects are less common and range from <1% to 13% for
      sorafenib, <1% to 16% for sunitinib, and 1% to 20% for temsirolimus. Overall,
      sunitinib causes the most grade 3/4 side effects and sorafenib causes the fewest
      grade 3/4 side effects, although head-to-head trials are required to compare
      safety profiles of all three kinase inhibitors. Virtually all side effects can be
      managed effectively. CONCLUSION: Prevention, recognition, and prompt management
      of side effects are of key importance and avoid unnecessary dose reductions,
      which may undermine treatment efficacy.

PMID- 18054826
TI  - Involvement of intestinal calcium transporter 1 and metallothionein in cadmium
      accumulation in the liver and kidney of mice fed a low-calcium diet.
AB  - Essential metals can affect the metabolism of nonessential metals. Calcium (Ca)
      is an essential mineral that is commonly lacking in the diet. When we fed 5-week
      old male mice for 4 weeks on a purified diet containing 0.005% Ca (CaDF mice),
      the Ca concentration in the plasma, liver and kidneys did not decreased. Cd
      accumulation increased in the liver and kidneys of CaDF mice given 1mg/kg Cd
      orally each day for 5 days, but not in those given intraperitoneal injections of
      Cd or Cd-metallothionein (Cd-MT). The zinc (Zn) concentration increased
      significantly in the intestinal cytosol and plasma during the time the mice were
      fed the low-Ca diet, and expression of both MT-1 and ZnT-1 sharply increased with
      a similar time course. Intestinal mRNA expression of CaT1, a Ca transporter, was
      more than 10 times higher in CaDF mice than in controls, although expression of
      other transporters, including DMT1, decreased in CaDF mice. These results suggest
      that CaT1 may stimulate the intestinal absorption of Cd and Zn, and some Cd may
      be distributed to the kidneys along with MT induced by Zn.

PMID- 18054827
TI  - Proteome analysis of Persian sturgeon (Acipenser persicus) ova.
AB  - The Persian sturgeon ova are a key material both for inevitable artificial
      propagation and for caviar production. In this study, the proteome profile of
      Persian sturgeon ova was analyzed using 2-DE and MALDI-TOF/TOF in order to
      determine its protein composition. Out of 192 spots analyzed with MALDI-TOF/TOF,
      107 spots corresponding to 73 different proteins were identified. The identified
      proteins were classified into 11 groups with regard to their main known function
      involving cell structure (24.65%), translation and transcription (12.32%),
      metabolism and energy production (12.32%), protein synthesis (9.60%), membrane
      protein receptors or cell signaling (8.21%), cell defense (5.47%), transport
      (5.47%), cell division (8.21%), vitellogenin (2.73%), unclassified (6.84%) and
      unknown function (4.10%). The results of this study provide a valuable resource
      for molecular analysis of normal and abnormal conditions affecting female
      reproduction. Moreover, it may help to better understand factors affecting caviar
      quality during refrigerated storage.

PMID- 18054828
TI  - Retention of data in heat-damaged SIM cards and potential recovery methods.
AB  - Examination of various SIM cards and smart card devices indicates that data may
      be retained in SIM card memory structures even after heating to temperatures up
      to 450 degrees C, which the National Institute of Standards and Technology (NIST)
      has determined to be approximately the maximum average sustained temperature at
      desk height in a house fire. However, in many cases, and certainly for
      temperatures greater than 450 degrees C, the SIM card chip has suffered
      structural or mechanical damage that renders simple probing or rewiring
      ineffective. Nevertheless, this has not necessarily affected the data, which is
      stored as charge in floating gates, and alternative methods for directly
      accessing the stored charge may be applicable.

PMID- 18054829
TI  - A novel way to investigate the effects of plasma exchange on antibiotic levels:
      use of microdialysis.
AB  - Plasma exchange (PE) is a treatment modality frequently used for many autoimmune
      diseases and may cause extracorporeal elimination of antibiotics. No data
      currently exist on antibiotic concentrations in extracellular fluid during PE.
      The aim of this study is to describe the effect of PE on the serum and
      subcutaneous tissue pharmacokinetics of piperacillin administered as a continuous
      infusion in a critically ill 17-year-old patient with Guillain-Barre syndrome and
      ventilator-associated pneumonia on Days 1 and 4 of antibiotic therapy. The effect
      of PE on piperacillin concentrations appears to be small. On Day 1, an estimated
      7% of total piperacillin eliminated during PE was attributable to PE. On Day 4
      this was estimated to be 11%. Using the in vivo sampling technique microdialysis,
      we have been able to show that a small redistribution of piperacillin from tissue
      to serum occurs in response to the reducing serum concentrations caused by PE. In
      critically ill patients, we believe that administration of a beta-lactam
      antibiotic by continuous infusion should be considered to maintain serum and
      tissue concentrations of these time-dependent antibiotics.

PMID- 18054830
TI  - A bienzyme channeling glucose sensor with a wide concentration range based on co
      entrapment of enzymes in SBA-15 mesopores.
AB  - A novel bienzyme-channeling sensor was constructed by entrapping glucose oxidase
      (GOD) and horseradish peroxidase (HRP) in the mesopores of well-ordered hexagonal
      mesoporous silica structures (SBA-15). The SBA-15 mesoporous materials
      accelerated the electron transfer between the entrapped HRP and electrode. Both
      HRP and GOD retained their catalytic activities in the bienzyme-entrapped SBA-15
      film. In presence of glucose the enzymatic reaction of GOD-glucose-dissolved
      oxygen system generated hydrogen peroxide in the bienzyme-entrapped mesopores,
      which was immediately reduced at -0.40 V by an electrocatalytic reaction with the
      HRP entrapped in the same mesopore to lead to a sensitive and fast amperometric
      response. Thus the bienzyme channeling could be used for the detection of glucose
      with excellent performance without the addition of any mediator. Optimization of
      the experimental parameters was performed with regard to pH, operating potential
      and temperature. The detection limit was down to 2.7 x 10(-7)M with a very wide
      linear range from 3.0 x 10(-6) to 3.4 x 10(-2)M. The constructed bienzyme
      channeling provided a strategy for amperometric detection of oxidase substrates
      by co-entrapping the corresponding oxidase and HRP in the mesoporous materials.

PMID- 18054831
TI  - Expression profiles in malignant fibrous histiocytomas: clues for differentiating
      'spindle cell' and 'pleomorphic' subtypes.
AB  - We analysed 21 samples of malignant fibrous histiocytoma (MFH) distinguished into
      the two principal morphological categories ('spindle cell' and the 'pleomorphic'
      subtypes). The aim of our study was to verify if a distinction between the two
      subclasses of MFH in terms of expression/activation of protein profiles could
      support and extend the morphological criteria. For this purpose, we carried out
      an immunohistochemical and immunoblotting analysis of proteins that could be
      relevant in sarcoma biology and potential diagnostic and therapeutical targets
      such as matrix metalloproteinases (MMPs) and molecules related to adhesive and
      proliferative properties. Our analysis revealed that MMP-1, MMP-9 expression and
      p27(kip1) cytoplasmic localisation can be considered valid parameters in the
      classification and potential explanation of the aggressive behaviour of this non
      homogeneous group of MFH.

PMID- 18054832
TI  - Delayed paraplegia associated with vertebral necrosis after type A dissection
      surgery.
AB  - Paraplegia is a rare complication of surgery for acute type A aortic dissection.
      We report a case of delayed postoperative paraplegia associated with necrosis of
      the thoracic vertebral bodies and soft tissue. The pathogenesis of delayed
      postoperative paraplegia is unknown, but our case report would strongly suggest
      ischemia of the descending thoracic intercostal arteries as the causative
      mechanism. The precipitating episode (respiratory distress syndrome with
      hemodynamic instability) might have promoted the compromised spinal circulation
      to become clinically evident in our patient. Treatment for this serious
      complication is mostly supportive, although CSF drainage may be helpful in the
      acute phase.

PMID- 18054833
TI  - Tracheo-carinal reconstructions using extrathoracic muscle flaps.
AB  - OBJECTIVES: Prospective evaluation of tracheo-carinal airway reconstructions
      using pedicled extrathoracic muscle flaps for closing airway defects after non
      circumferential resections and after carinal resections as part of the
      reconstruction for alleviation of anastomotic tension. METHODS: From January 1996
      to June 2006, 41 patients underwent tracheo-carinal airway reconstructions using
      45 extrathoracic muscle flaps (latissimus dorsi, n=25; serratus anterior, n=18;
      pectoralis major, n=2) for closing airway defects resulting from (a)
      bronchopleural fistulas (BPF) with short desmoplastic bronchial stumps after
      right upper lobectomy (n=1) and right-sided (pleuro) pneumonectomy (n=13); (b)
      right (n=9) and left (n=3) associated with partial carinal resections for pre
      treated centrally localised tumours; (c) partial non-circumferential tracheal
      resections for pre-treated tracheal tumours, tracheo-oesophageal fistulas (TEF)
      and chronic tracheal injury with tracheomalacia (n=11); (d) carinal resections
      with the integration of a muscle patch in specific parts of the anastomotic
      reconstruction for alleviation of anastomotic tension (n=4). The airway defects
      ranged from 2 x 1 cm to 8 x 4 cm and involved up to 50% of the airway
      circumference. The patients were followed by clinical examination, repeated
      bronchoscopy, pulmonary function testing and CT scans. The minimum follow-up time
      was 6 months. RESULTS: Ninety-day mortality was 7.3% (3/41 patients). Four
      patients (9.7%) sustained muscle flap necrosis requiring re-operation and flap
      replacement without subsequent mortality, airway dehiscence or stenosis. Airway
      dehiscence was observed in 1/41 patients (2.4%) and airway stenosis in 1/38
      surviving patients (2.6%) responding well to topical mitomycin application.
      Follow-up on clinical grounds, by CT scans and repeated bronchoscopy, revealed
      airtight, stable and epithelialised airways and no recurrence of BPF or TEF in
      all surviving patients. CONCLUSIONS: Tracheo-carinal airway defects can be closed
      by use of pedicled extrathoracic muscle flaps after non-circumferential
      resections and after carinal resections with the muscle patch as part of the
      reconstruction for alleviation of anastomotic tension.

PMID- 18054834
TI  - Structural correlates of psychopathological symptom dimensions in schizophrenia:
      a voxel-based morphometric study.
AB  - Structural neuroimaging has substantially advanced the neurobiological research
      of schizophrenia by describing a range of focal brain alterations as possible
      neuroanatomical underpinnings of the disease. Despite this progress, a
      considerable heterogeneity of structural findings persists that may reflect the
      phenomenological diversity of schizophrenia. It is unclear whether the range of
      possible clinical disease manifestations relates to a core structural brain
      deficit or to distinct structural correlates. Therefore, gray matter density
      (GMD) differences between 175 schizophrenic patients (SZ) and 177 matched healthy
      control subjects (HC) were examined in a three-step approach using cross
      sectional and conjunctional voxel-based morphometry (VBM): (1) analysis of
      structural alterations irrespective of symptomatology; (2) subdivision of the
      patient sample according to a three-dimensional factor model of the PANSS and
      investigation of structural differences between these subsamples and healthy
      controls; (3) analysis of a common pattern of structural alterations present in
      all patient subsamples compared to healthy controls. Significant GMD reductions
      in patients compared to controls were identified within the prefrontal, limbic,
      paralimbic, temporal and thalamic regions. The disorganized symptom dimension was
      associated with bilateral alterations in temporal, insular and medial prefrontal
      cortices. Positive symptoms were associated with left-pronounced alterations in
      perisylvian regions and extended thalamic GMD losses. Negative symptoms were
      linked to the most extended alterations within orbitofrontal, medial prefrontal,
      lateral prefrontal and temporal cortices as well as limbic and subcortical
      structures. Thus, structural heterogeneity in schizophrenia may relate to
      specific patterns of GMD reductions that possibly share a common prefrontal
      perisylvian pattern of structural brain alterations.

PMID- 18054835
TI  - Lens and cornea: the "refracton hypothesis".

PMID- 18054836
TI  - Review of factors essential for blastocyst implantation for their modulating
      effects on the maternal immune system.
AB  - Pituitary and ovarian hormones prepare the endometrium for successful blastocyst
      implantation and support its process directly or indirectly through the action of
      growth factors, cytokines and other molecules. Many of the blastocyst
      implantation essential factors (BIEFs) are modulators of the maternal immune
      system. Since little is known as to the action of these molecules on the uterine
      lymphocytes, its clarification is imperative to the understanding of the process
      of blastocyst implantation.

PMID- 18054838
TI  - Synthesis and spectral investigation of Al(III) catechin/beta-cyclodextrin and
      Al(III) quercetin/beta-cyclodextrin inclusion compounds.
AB  - Al-catechin/beta-cyclodextrin and Al-quercetin/beta-cyclodextrin (beta-CD)
      inclusion compounds were synthesized and characterized by IR, UV-vis, 1H and 13C
      NMR and TG and DTA analyses. Because quercetin is sparingly soluble in water, the
      stability constants of the Al-quercetin/beta-CD and Al-catechin/beta-CD compounds
      were determined by phase solubility studies. The AL-type diagrams indicated the
      formation of 1:1 inclusion compounds and allowed calculation of the stability
      constants. The thermodynamic parameters were obtained from the dependence of the
      stability constants on temperature and results indicated that the formation of
      the inclusion compounds is an enthalpically driven process. The thermal
      decomposition of the solid Al-quercetin/beta-CD and Al-catechin/beta-CD inclusion
      compounds took place at different stages, compared with the respective
      precursors, proving that an inclusion complexation process really occurred.

PMID- 18054839
TI  - Infrared and infrared emission spectroscopy of the zinc carbonate mineral
      smithsonite.
AB  - Infrared emission and infrared spectroscopy has been used to study a series of
      selected natural smithsonites from different origins. An intense broad infrared
      band at 1440 cm(-1) is assigned to the nu3 CO3(2-) antisymmetric stretching
      vibration. An additional band is resolved at 1335 cm(-1). An intense sharp Raman
      band at 1092 cm(-1) is assigned to the CO3(2-) symmetric stretching vibration.
      Infrared emission spectra show a broad antisymmetric band at 1442 cm(-1) shifting
      to lower wavenumbers with thermal treatment. A band observed at 870 cm(-1) with a
      band of lesser intensity at 842 cm(-1) shifts to higher wavenumbers upon thermal
      treatment and is observed at 865 cm(-1) at 400 degrees C and is assigned to the
      CO3(2-)nu2 mode. No nu2 bending modes are observed in the Raman spectra for
      smithsonite. The band at 746 cm(-1) shifts to 743 cm(-1) at 400 degrees C and is
      attributed to the CO3(2-)nu4 in phase bending modes. Two infrared bands at 744
      and around 729 cm(-1) are assigned to the nu4 in phase bending mode. Multiple
      bands may be attributed to the structural distortion ZnO6 octahedron. This
      structural distortion is brought about by the substitution of Zn by some other
      cation. A number of bands at 2499, 2597, 2858, 2954 and 2991 cm(-1) in both the
      IE and infrared spectra are attributed to combination bands.

PMID- 18054840
TI  - New advances in the diagnosis of congenital cytomegalovirus infection.
AB  - Although the diagnosis of congenital CMV infection is still complex, important
      goals have been achieved in recent years, among which are: the availability of
      more reliable IgM tests for screening pregnant women whose pre-pregnancy
      serological status for CMV is unknown, tests to determine the avidity index of
      anti-CMV IgG, allowing the diagnosis of a primary CMV infection and innovative
      and traditional virological tests to detect the virus in amniotic fluid. When a
      woman is found to be IgM-positive, further diagnostic evaluation focused on
      determining whether this is due to a primary infection should be carried out.
      Maternal primary infections that were difficult to determine until a few years
      ago unless documented by seroconversions can now be readily diagnosed from the
      presence of low/moderate avidity anti-CMV antibody which persists for
      approximately 18-20 weeks after primary infection. In mothers at risk of
      transmitting the virus prenatal diagnosis can be performed between 21 and 22
      weeks of gestation, and the amniotic fluid represents the pathological material
      of choice to determine intrauterine virus transmission. At birth or in the first
      2/3 weeks of life, it is essential to use appropriate tests for diagnosis of CMV
      congenital infection.

PMID- 18054841
TI  - Vaccination approaches to combat human metapneumovirus lower respiratory tract
      infections.
AB  - Human metapneumovirus (hMPV) was discovered in 2001 as a causative agent of
      respiratory disease in young children, immunocompromised individuals and the
      elderly. Clinical signs of hMPV infection range from mild respiratory illness to
      bronchiolitis and pneumonia. Two main genetic lineages of hMPV that circulate
      worldwide were found to be antigenically different, but antibodies against the F
      protein, the major determinant of protection, were shown to be cross-protective.
      Since the discovery of hMPV in 2001, several research groups have developed
      vaccine candidates that may be used to protect different risk groups against hMPV
      induced respiratory disease. The studies in rodent and non-human primate models
      look promising, but none of the vaccine candidates has been tested yet in human
      volunteers. Here we give an overview of the immunogenicity and protective
      efficacy of a variety of live attenuated, virus vectored, inactivated virus and
      subunit vaccines that have been tested in animal models.

PMID- 18054842
TI  - Effect of oral contraceptive cycle phase on performance in team sport players.
AB  - The purpose of this study was to examine whether common team sport performance
      variables (anaerobic power, reactive strength and repeat sprint ability) are
      affected by acute hormonal fluctuation within a monophasic oral contraceptive
      (OC) cycle. Ten female team sport athletes completed performance tests at three
      time points of a single OC cycle, during the consumption phase (CONS), early
      (WITH1) and late in the withdrawal phase (WITH2). Tests included drop jumps (30cm
      and 45cm heights), a counter movement jump, a 10s cycle sprint test and a 5x 6s
      repeated sprint cycle test. Resting endogenous serum oestradiol and progesterone
      concentrations were also measured. No significant differences were observed
      between phases for the counter movement jump and cycle tests (total work and peak
      power). Reactive strength measured from the 30cm drop height was significantly
      lower during WITH2 (162+/-38cms(-1)) compared to both CONS (177+/-44cms(-1)) and
      WITH1 (178+/-40cms(-1)) (p<0.05). Reactive strength measured from the 45cm drop
      height was significantly higher in CONS (178+/-48cms(-1)) compared to both WITH1
      and WITH2 (161+/-39cms(-1) and 158+/-29cms(-1), respectively) (p<0.05). Serum
      oestradiol levels were greater during WITH2 compared to both WITH1 and CONS
      (p<0.05) but there was no difference in serum progesterone levels. The results
      demonstrate that for female team sport athletes, only reactive strength varied
      significantly throughout an OC cycle, possibly due to the action of hormones on
      neuromuscular timing and the stretch-shortening cycle.

PMID- 18054843
TI  - Daily step counts and selected coronary heart disease risk factors in adolescent
      girls.
AB  - Data on objectively determined physical activity (PA) behaviour of Australian
      adolescent girls is lacking along with known associations between PA behaviour
      and future risk of coronary heart disease (CHD). The purpose of this study was to
      measure four consecutive days of pedometer steps and the prevalence of selected
      CHD risk factors in a cross-sectional sample of 415 Australian adolescent girls
      (age 16+/-0.8 year; mean+/-S.D.). Coronary heart disease risk factors assessed
      were low levels of daily PA (<10,000stepsday(-1)), high-blood pressure (>95th
      percentile), overweight (>85th percentile) and/or obese (>95th percentile),
      presence of family history of heart disease, low cardio-respiratory fitness (poor
      estimated VO(2)max), and being a smoker. Overall, 41.2% of the sample had > or =2
      factors. The mean number of steps per day was 9617+/-3108 (mean+/-S.D.). There
      was a significant relationship between daily ambulatory activity of <10,000 steps
      and poor cardiovascular fitness (Odds Ratios [OR]=2.15, confidence intervals
      [CI]=1.02-4.54). When girls in the highest and lowest quartiles of pedometer
      steps were compared, those classified as inactive were significantly more likely
      to be obese (OR=4.70, CI=1.17-18.60), less likely to be underweight (OR=0.29,
      CI=0.09-0.88), and had poor cardiovascular fitness (OR=3.27, CI=1.35-7.93). All
      of 47 participants who had > or =3 CHD risk factors were also classified as
      inactive (<7409 steps). This study demonstrates a relationship between daily step
      counts and selected measures of CHD risk factors in adolescent girls.

PMID- 18054844
TI  - Diminished baroreflex-induced vasoconstriction following alpha-2 adrenergic
      receptor blockade in humans.
AB  - The relative contribution of alpha adrenergic receptor subtypes in the
      transduction of sympathetic nerve activity (SNA) during carotid baroreflex (CBR)
      engagement is not well understood. Therefore, we compared the hemodynamic
      consequence of CBR-mediated sympatho-excitation via neck pressure (NP) before and
      after alpha-2 adrenergic blockade with intra-arterial yohimbine. Leg blood flow
      was measured using 2D and Doppler ultrasound, and arterial blood pressure was
      determined directly. NP caused the expected vasoconstriction, and this response
      was significantly reduced (by 50-60%) when NP was repeated after yohimbine. These
      data indicate that alpha-2 adrenergic receptors contribute significantly to CBR
      induced vasoconstriction in the human leg under resting conditions.

PMID- 18054845
TI  - Increases in inspiratory neural drive in response to rapid oscillating airflow
      braking forces (vibration).
AB  - OBJECTIVE: To investigate whether 10 breaths against a vibration stimulus elicits
      increments of spontaneous and maximal inspiratory mouth pressure (maxMP) and
      tidal mean inspiratory flow (iV(T)/T(I)) upon stimulus removal. METHODS: Twelve
      healthy subjects (8 female, 4 male; 22-50 years old), recruited from the
      University student body, completed 3 maximal inspirations before (pre) and after
      (post) 10 inspirations against resistive loading with a vibration-type stimulus
      (VIB; youbreathe, Exoscience Ltd., London, UK), pressure-matched resistive
      loading (RES) or resting breathing (CON; no load). The trials were presented in a
      random order. maxMP and involuntary tidal breathing were compared pre and post
      conditioning. RESULTS: Inspiratory neural drive increased only after VIB as
      evidenced by increased tidal and maxMP and mean inspiratory flow (iV(T)/T(I); p <
      0.05). There was no effect of either resistance or control breathing on maximal
      maxMP or tidal responses. CONCLUSIONS: Ten conditioning breaths of VIB lead to
      increased maximal inspiratory mouth pressure and spontaneous mouth pressure and
      mean inspiratory flow possibly through a common mechanism of increased descending
      respiratory drive.

PMID- 18054846
TI  - A highly sensitive assay for ritodrine in human serum by hydrophilic interaction
      chromatography-tandem mass spectrometry.
AB  - We developed a sensitive assay for ritodrine (RTD), a beta2-adrenergic agonist,
      in human serum. This method was based upon the selective and sensitive technique
      by a tandem mass spectrometry (MS/MS) using a hydrophilic interaction
      chromatography (HILIC) technique. This method involved a mixed-mode cation
      exchange solid-phase extraction of RTD and isoxsuprine, the internal standard
      (IS), from serum with Waters Oasis MCX cartridges. The detection was made using a
      Micromass Quattromicro API LC-MS/MS system with electrospray ionization source in
      positive ion mode. The separation of the analytes was achieved within 4 min on a
      silica column with a mobile phase of ammonium acetate (10 mM, pH 4.5) and
      acetonitrile (10:90, v/v). Multiple reaction monitoring was utilized by
      monitoring 288.2-->121.1 for RTD, 302.2-->107.0 for IS. The calibration curve for
      RTD was linear over a range of 0.5-1000 ng/mL. When 50 microL serum was used for
      extraction, the lower limit of quantification was 0.39 ng/mL (97.5 fg on-column).
      The percent coefficient of validation for accuracy and precision (inter- and
      intra-day) was less than 9.8% and the recovery was ranged from 83.5 to 94.7% for
      RTD. This method enabled us to successfully determine RTD in maternal and fetal
      sera.

PMID- 18054847
TI  - Efficacy of doxorubicin coupled to lactosaminated albumin on rat hepatocellular
      carcinomas evaluated by ultrasound imaging.
AB  - BACKGROUND/AIMS: Doxorubicin was conjugated with lactosaminated human albumin, a
      hepatotropic drug carrier, in order to increase its efficacy in the treatment of
      hepatocellular carcinoma. In rats bearing hepatocellular carcinomas induced by
      diethylnitrosamine, lactosaminated human albumin coupled doxorubicin enhanced the
      drug concentrations in the tumours and lowered those in extrahepatic tissues. The
      aim of the present study was to investigate the effects of lactosaminated human
      albumin coupled doxorubicin on the growth of established rat hepatocellular
      carcinomas induced by diethylnitrosamine. METHODS: Lactosaminated human albumin
      coupled doxorubicin and the free drug were i.v. administered to rats twice a week
      for 4 weeks at the single dose of 1 microg/g. Growth of individual tumours was
      followed through time by ultrasonography. RESULTS: In the control animals
      injected with saline the mean area of the tracked tumours significantly increased
      during the whole period of treatment. In the group of rats treated with
      lactosaminated human albumin coupled doxorubicin the mean area of the followed
      hepatocellular carcinomas remained practically unchanged. The free drug inhibited
      tumour growth only in the first period of drug administration. Lactosaminated
      human albumin coupled doxorubicin also hindered the development of new neoplastic
      nodules, which was unaffected by the free drug. CONCLUSIONS: The results support
      lactosaminated human albumin coupled doxorubicin as a promising agent for a
      systemic chemotherapy of hepatocellular carcinomas to treat noncurable patients.

PMID- 18054848
TI  - Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty
      liver disease.
AB  - BACKGROUND: Long-chain polyunsaturated fatty acid omega-3 levels are decreased in
      the hepatic tissue of patients with nonalcoholic fatty liver disease.
      Polyunsaturated fatty acids are negative regulators of hepatic lipogenesis and
      attenuate the inflammatory response in mice. AIM: To investigate whether
      polyunsaturated fatty acid may be effective in the treatment of nonalcoholic
      fatty liver disease. METHODS: Forty patients with nonalcoholic fatty liver
      disease were randomized into two groups for treatment of 6 months duration. Group
      DP (n=20) received an AHA recommended diet and polyunsaturated fatty acid 2g/day;
      Group D (n=20) received only the AHA regular diet. Outcome measurements were
      fatty liver assessed by abdominal ultrasound, liver aminotransferase and tumour
      necrosis factor-alpha serum levels, and insulin resistance assessed by HOMA(IR).
      RESULTS: After 6 months of treatment, the DP group displayed a decrease in
      alanine aminotransferase levels (p<0.01), as well as in triglyceride levels
      (p<0.01), serum tumour necrosis factor-alpha levels (p<0.05) and in HOMA(IR)
      (p<0.05). In the D group, no significant modification was observed. In the DP
      group, complete fatty liver regression was observed in 33.4% of the patients, and
      an overall reduction in 50%. In contrast, no patient achieved complete regression
      in the D group, whereas some amount of reduction occurred in 27.7% of the
      patients; the remaining 72.2% did not change. CONCLUSION: Our results indicate
      that alanine aminotransferase, triglyceride and serum tumour necrosis factor
      alpha levels, as well as fatty liver improved after polyunsaturated fatty acid
      administration.

PMID- 18054849
TI  - Refractory ulcerative colitis and iatrogenic colorectal Kaposi's sarcoma.
AB  - Colorectal Kaposi's sarcoma, a human herpes virus-8 associated mesenchymal
      tumour, is exceedingly rare in human immunodeficiency virus-negative subjects and
      almost always reported in association with severe, refractory, inflammatory bowel
      disease. In this paper we report a case--the second from Italy--of a colorectal
      Kaposi's sarcoma in a human immunodeficiency virus-negative, heterosexual man
      with severe refractory ulcerative colitis. Kaposi's sarcoma developed after
      starting glucocorticosteroid therapy, supporting the theory that colorectal
      Kaposi's sarcoma associated with ulcerative colitis is iatrogenic.

PMID- 18054850
TI  - Contrast-enhanced ultrasound assessment of arterial vascularization of small
      nodules arising in the cirrhotic liver.
AB  - BACKGROUND AND AIM: Aim of this study was to compare contrast-enhanced ultrasound
      and multi-detector row computed tomography in detecting arterial hypervascularity
      in small cirrhotic nodules. PATIENTS AND METHODS: Sixty-two nodules (41 measuring
      1.0-2.0 cm, 21 measuring 2.1-3.0 cm) found in 55 cirrhotic patients were examined
      with both methods. Lesions displaying arterial hypervascularity with washout in
      the portal/venous phase on both studies were considered hepatocellular carcinomas
      and treated; all other nodules were subjected to ultrasound-guided fine-needle
      biopsy. RESULTS: The larger nodules (2.1-3.0 cm) included 19 hepatocellular
      carcinomas (90%), 1 macroregenerative nodule type I and 1 macroregenerative
      nodule type II; 35 (87%) of the smaller nodules were hepatocellular carcinomas, 2
      were macroregenerative nodules type I, 2 macroregenerative nodules type II and 2
      hemangiomas. The two studies yielded concordant findings for 54 nodules (87%),
      including 46 hypervascular on both examinations and 8 that were consistently
      hypovascular. Two of the latter nodules were hepatocellular carcinomas. The other
      eight nodules displayed arterial hypervascularity on only one of the studies. Six
      of these (75%) were hepatocellular carcinomas, including five that were negative
      in the contrast-enhanced ultrasound study. CONCLUSION: Computed tomography and
      contrast-enhanced ultrasound show high agreement in the vascular classification
      of small nodules detected by ultrasound in cirrhotic livers, although the former
      technique was slightly more sensitive in the detection of arterial
      hypervascularization.

PMID- 18054851
TI  - Early vision is early in time.
AB  - Roelfsema, Tolboom, and Khayat have found that neurons in primary visual cortex,
      V1, increase their spike firing rates to signal image segmentation and attention.
      V1 responses were in a temporal sequence: first to image motion, next to
      segmentation, last to attentional signals. The involvement of V1 with
      segmentation and attention suggests modifying the hierarchical view of visual
      perception.

PMID- 18054852
TI  - Keeping in check painful synapses in central amygdala.
AB  - Glutamatergic projections from the parabrachial nucleus to the central amygdala
      are implicated in pain transmission. In this issue of Neuron, Delaney et al.
      identify a new form of adrenergic modulation at these synapses, demonstrating
      that noradrenaline-induced suppression of glutamate release is mediated by a
      decrease in the number of sites of synaptic transmission without changes in
      probability of release.

PMID- 18054853
TI  - Wilder Penfield in the age of YouTube: visualizing the sequential activation of
      sensorimotor areas across neocortex.
AB  - Flow of electrical activity across neocortex is essential for many sensorimotor
      tasks. Whether this flow is localized or spreads widely is unknown. Ferezou et
      al., imaging activity across the cortical mantle in awake mice, show in this
      issue of Neuron that touch by a single vibrissa leads to a rapid depolarization
      of primary sensory and motor areas that subsequently spreads across most of
      cortex.

PMID- 18054854
TI  - Activation of GABAA receptors: views from outside the synaptic cleft.
AB  - Some GABA(A) receptors (GABA(A)Rs) are activated by low transmitter levels
      present in the extracellular space and generate an uninterrupted conductance
      referred to as "tonic." This tonic conductance is highly sensitive to all factors
      regulating the amount of GABA surrounding the neurons. Only a few GABA(A)Rs with
      particular subunit combinations are well suited to mediate the tonic conductance.
      These same receptors constitute important and specific targets for various
      endogenous and exogenous neuroactive compounds and possible therapeutic targets.

PMID- 18054856
TI  - Different processing phases for features, figures, and selective attention in the
      primary visual cortex.
AB  - Our visual system imposes structure onto images that usually contain a diversity
      of surfaces, contours, and colors. Psychological theories propose that there are
      multiple steps in this process that occur in hierarchically organized regions of
      the cortex: early visual areas register basic features, higher areas bind them
      into objects, and yet higher areas select the objects that are relevant for
      behavior. Here we test these theories by recording from the primary visual cortex
      (area V1) of monkeys. We demonstrate that the V1 neurons first register the
      features (at a latency of 48 ms), then segregate figures from the background
      (after 57 ms), and finally select relevant figures over irrelevant ones (after
      137 ms). We conclude that the psychological processing stages map onto distinct
      time episodes that unfold in the visual cortex after the presentation of a new
      stimulus, so that area V1 may contribute to all these processing steps.

PMID- 18054855
TI  - Inhibition and brain work.
AB  - The major part of the brain's energy budget ( approximately 60%-80%) is devoted
      to its communication activities. While inhibition is critical to brain function,
      relatively little attention has been paid to its metabolic costs. Understanding
      how inhibitory interneurons contribute to brain energy consumption (brain work)
      is not only of interest in understanding a fundamental aspect of brain function
      but also in understanding functional brain imaging techniques which rely on
      measurements related to blood flow and metabolism. Herein we examine issues
      relevant to an assessment of the work performed by inhibitory interneurons in the
      service of brain function.

PMID- 18054857
TI  - Tiling of r7 axons in the Drosophila visual system is mediated both by
      transduction of an activin signal to the nucleus and by mutual repulsion.
AB  - The organization of neuronal wiring into layers and columns is a common feature
      of both vertebrate and invertebrate brains. In the Drosophila visual system, each
      R7 photoreceptor axon projects within a single column to a specific layer of the
      optic lobe. We refer to the restriction of terminals to single columns as tiling.
      In a genetic screen based on an R7-dependent behavior, we identified the Activin
      receptor Baboon and the nuclear import adaptor Importin-alpha3 as being required
      to prevent R7 axon terminals from overlapping with the terminals of R7s in
      neighboring columns. This tiling function requires the Baboon ligand, dActivin,
      the transcription factor, dSmad2, and retrograde transport from the growth cone
      to the R7 nucleus. We propose that dActivin is an autocrine signal that restricts
      R7 growth cone motility, and we demonstrate that it acts in parallel with a
      paracrine signal that mediates repulsion between R7 terminals.

PMID- 18054858
TI  - Gating of Sema3E/PlexinD1 signaling by neuropilin-1 switches axonal repulsion to
      attraction during brain development.
AB  - The establishment of functional neural circuits requires the guidance of axons in
      response to the actions of secreted and cell-surface molecules such as the
      semaphorins. Semaphorin 3E and its receptor PlexinD1 are expressed in the brain,
      but their functions are unknown. Here, we show that Sema3E/PlexinD1 signaling
      plays an important role in initial development of descending axon tracts in the
      forebrain. Early errors in axonal projections are reflected in behavioral
      deficits in Sema3E null mutant mice. Two distinct signaling mechanisms can be
      distinguished downstream of Sema3E. On corticofugal and striatonigral neurons
      expressing PlexinD1 but not Neuropilin-1, Sema3E acts as a repellent. In
      contrast, on subiculo-mammillary neurons coexpressing PlexinD1 and Neuropilin-1,
      Sema3E acts as an attractant. The extracellular domain of Neuropilin-1 is
      sufficient to convert repulsive signaling by PlexinD1 to attraction. Our data
      therefore reveal a "gating" function of neuropilins in semaphorin-plexin
      signaling during the assembly of forebrain neuronal circuits.

PMID- 18054860
TI  - Activity-dependent plasticity in an olfactory circuit.
AB  - Olfactory sensory neurons (OSNs) form synapses with local interneurons and second
      order projection neurons to form stereotyped olfactory glomeruli. This primary
      olfactory circuit is hard-wired through the action of genetic cues. We asked
      whether individual glomeruli have the capacity for stimulus-evoked plasticity by
      focusing on the carbon dioxide (CO2) circuit in Drosophila. Specialized OSNs
      detect this gas and relay the information to a dedicated circuit in the brain.
      Prolonged exposure to CO2 induced a reversible volume increase in the CO2
      specific glomerulus. OSNs showed neither altered morphology nor function after
      chronic exposure, but one class of inhibitory local interneurons showed
      significantly increased responses to CO2. Two-photon imaging of the axon
      terminals of a single PN innervating the CO2 glomerulus showed significantly
      decreased functional output following CO2 exposure. Behavioral responses to CO2
      were also reduced after such exposure. We suggest that activity-dependent
      functional plasticity may be a general feature of the Drosophila olfactory
      system.

PMID- 18054859
TI  - Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the
      MAGUK family member CASK.
AB  - Synaptogenesis is a highly regulated process that underlies formation of neural
      circuitry. Considerable work has demonstrated the capability of some adhesion
      molecules, such as SynCAM and Neurexins/Neuroligins, to induce synapse formation
      in vitro. Furthermore, Cdk5 gain of function results in an increased number of
      synapses in vivo. To gain a better understanding of how Cdk5 might promote
      synaptogenesis, we investigated potential crosstalk between Cdk5 and the cascade
      of events mediated by synapse-inducing proteins. One protein recruited to
      developing terminals by SynCAM and Neurexins/Neuroligins is the MAGUK family
      member CASK. We found that Cdk5 phosphorylates and regulates CASK distribution to
      membranes. In the absence of Cdk5-dependent phosphorylation, CASK is not
      recruited to developing synapses and thus fails to interact with essential
      presynaptic components. Functional consequences include alterations in calcium
      influx. Mechanistically, Cdk5 regulates the interaction between CASK and liprin
      alpha. These results provide a molecular explanation of how Cdk5 can promote
      synaptogenesis.

PMID- 18054863
TI  - Noradrenaline modulates transmission at a central synapse by a presynaptic
      mechanism.
AB  - The lateral division of the central amygdala (CeAL) is the target of ascending
      fibers from the pain-responsive and stress-responsive nuclei in the brainstem. We
      show that single fiber inputs from the nociceptive pontine parabrachial nucleus
      onto CeAL neurons form suprathreshold glutamatergic synapses with multiple
      release sites. Noradrenaline, acting at presynaptic alpha2 receptors, potently
      inhibits this synapse. This inhibition results from a decrease in the number of
      active release sites with no change in release probability. Introduction of a
      presynaptic scavenger of Gbetagamma subunits blocked the effects of
      noradrenaline, and botulinum toxin A reduced its effects, showing a direct action
      of betagamma subunits on the release machinery. These data illustrate a mechanism
      of presynaptic modulation where the output of a large multiple-release-site
      synapse is potently regulated by endogenously released noradrenaline and suggests
      that the CeA may be a target for the central nociceptive actions of
      noradrenaline.

PMID- 18054861
TI  - Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter
      GAT-1.
AB  - GABA transporters play an important but poorly understood role in neuronal
      inhibition. They can reverse, but this is widely thought to occur only under
      pathological conditions. Here we use a heterologous expression system to show
      that the reversal potential of GAT-1 under physiologically relevant conditions is
      near the normal resting potential of neurons and that reversal can occur rapidly
      enough to release GABA during simulated action potentials. We then use paired
      recordings from cultured hippocampal neurons and show that GABAergic transmission
      is not prevented by four methods widely used to block vesicular release. This
      nonvesicular neurotransmission was potently blocked by GAT-1 antagonists and was
      enhanced by agents that increase cytosolic [GABA] or [Na(+)] (which would
      increase GAT-1 reversal). We conclude that GAT-1 regulates tonic inhibition by
      clamping ambient [GABA] at a level high enough to activate high-affinity GABA(A)
      receptors and that transporter-mediated GABA release can contribute to phasic
      inhibition.

PMID- 18054862
TI  - A role for synaptic inputs at distal dendrites: instructive signals for
      hippocampal long-term plasticity.
AB  - Synaptic potentials originating at distal dendritic locations are severely
      attenuated when they reach the soma and, thus, are poor at driving somatic
      spikes. Nonetheless, distal inputs convey essential information, suggesting that
      such inputs may be important for compartmentalized dendritic signaling. Here we
      report a new plasticity rule in which stimulation of distal perforant path inputs
      to hippocampal CA1 pyramidal neurons induces long-term potentiation at the CA1
      proximal Schaffer collateral synapses when the two inputs are paired at a precise
      interval. This subthreshold form of heterosynaptic plasticity occurs in the
      absence of somatic spiking but requires activation of both NMDA receptors and
      IP(3) receptor-dependent release of Ca(2+) from internal stores. Our results
      suggest that direct sensory information arriving at distal CA1 synapses through
      the perforant path provide compartmentalized, instructive signals that assess the
      saliency of mnemonic information propagated through the hippocampal circuit to
      proximal synapses.

PMID- 18054864
TI  - Nociceptive tuning by stem cell factor/c-Kit signaling.
AB  - The molecular mechanisms regulating the sensitivity of sensory circuits to
      environmental stimuli are poorly understood. We demonstrate here a central role
      for stem cell factor (SCF) and its receptor, c-Kit, in tuning the responsiveness
      of sensory neurons to natural stimuli. Mice lacking SCF/c-Kit signaling displayed
      profound thermal hypoalgesia, attributable to a marked elevation in the thermal
      threshold and reduction in spiking rate of heat-sensitive nociceptors. Acute
      activation of c-Kit by its ligand, SCF, resulted in a reduced thermal threshold
      and potentiation of heat-activated currents in isolated small-diameter neurons
      and thermal hyperalgesia in mice. SCF-induced thermal hyperalgesia required the
      TRP family cation channel TRPV1. Lack of c-Kit signaling during development
      resulted in hypersensitivity of discrete mechanoreceptive neuronal subtypes.
      Thus, c-Kit can now be grouped with a small family of receptor tyrosine kinases,
      including c-Ret and TrkA, that control the transduction properties of sensory
      neurons.

PMID- 18054865
TI  - Spatiotemporal dynamics of cortical sensorimotor integration in behaving mice.
AB  - Tactile information is actively acquired and processed in the brain through
      concerted interactions between movement and sensation. Somatosensory input is
      often the result of self-generated movement during the active touch of objects,
      and conversely, sensory information is used to refine motor control. There must
      therefore be important interactions between sensory and motor pathways, which we
      chose to investigate in the mouse whisker sensorimotor system. Voltage-sensitive
      dye was applied to the neocortex of mice to directly image the membrane potential
      dynamics of sensorimotor cortex with subcolumnar spatial resolution and
      millisecond temporal precision. Single brief whisker deflections evoked highly
      distributed depolarizing cortical sensory responses, which began in the primary
      somatosensory barrel cortex and subsequently excited the whisker motor cortex.
      The spread of sensory information to motor cortex was dynamically regulated by
      behavior and correlated with the generation of sensory-evoked whisker movement.
      Sensory processing in motor cortex may therefore contribute significantly to
      active tactile sensory perception.

PMID- 18054867
TI  - Breast-cancer awareness: too much of a good thing?

PMID- 18054866
TI  - Disruption of large-scale brain systems in advanced aging.
AB  - Cognitive decline is commonly observed in advanced aging even in the absence of
      disease. Here we explore the possibility that normal aging is accompanied by
      disruptive alterations in the coordination of large-scale brain systems that
      support high-level cognition. In 93 adults aged 18 to 93, we demonstrate that
      aging is characterized by marked reductions in normally present functional
      correlations within two higher-order brain systems. Anterior to posterior
      components within the default network were most severely disrupted with age.
      Furthermore, correlation reductions were severe in older adults free from
      Alzheimer's disease (AD) pathology as determined by amyloid imaging, suggesting
      that functional disruptions were not the result of AD. Instead, reduced
      correlations were associated with disruptions in white matter integrity and poor
      cognitive performance across a range of domains. These results suggest that
      cognitive decline in normal aging arises from functional disruption in the
      coordination of large-scale brain systems that support cognition.

PMID- 18054868
TI  - Breast-cancer risk in BRCA-mutation-negative women from BRCA-mutation-positive
      families.

PMID- 18054869
TI  - Translation, please.

PMID- 18054870
TI  - Breast cancer genomics: real-time use.

PMID- 18054871
TI  - Intrauterine factors and breast cancer risk.

PMID- 18054872
TI  - Onto solid footing.

PMID- 18054873
TI  - When drugs are worth more than gold!

PMID- 18054874
TI  - Cancer survival statistics should be viewed with caution.

PMID- 18054875
TI  - Cancer survival statistics should be viewed with caution.

PMID- 18054877
TI  - Benign causes of increased serum CA-125 concentration.

PMID- 18054878
TI  - Mitigating radiation-induced cognitive impairment.

PMID- 18054879
TI  - Intrauterine factors and risk of breast cancer: a systematic review and meta
      analysis of current evidence.
AB  - BACKGROUND: Emerging evidence suggests an association between female prenatal
      experience and her subsequent risk of developing breast cancer. Potential
      underlying mechanisms include variation in amounts of maternal endogenous sex
      hormones and growth hormones, germ-cell mutations, formation of cancer stem
      cells, and other genetic or epigenetic events. We reviewed and summarised
      quantitatively the available data on intrauterine exposures and risk of breast
      cancer. METHODS: We systematically searched for studies that assessed association
      between perinatal factors and risk of breast cancer. We reviewed separately each
      of the perinatal factors, including birthweight, birth length, parental age at
      delivery, gestational age, intrauterine exposure to diethylstilbestrol, twin
      membership, maternal pre-eclampsia or eclampsia, and other factors. FINDINGS: We
      identified 57 studies published between Oct 1, 1980, and June 21, 2007. Increased
      risk of breast cancer was noted with increased birthweight (relative risk [RR]
      1.15 [95% CI 1.09-1.21]), birth length (1.28 [1.11-1.48]), higher maternal age
      (1.13 [1.02-1.25]), and paternal age (1.12 [1.05-1.19]). Decreased risk of breast
      cancer was noted for maternal pre-eclampsia and eclampsia (0.48 [0.30-0.78]) and
      twin membership (0.93 [0.87-1.00]). No association was noted between risk of
      breast cancer and gestational age at birth (0.95 [0.71-1.26]) or maternal
      diethylstilbestrol treatment (1.40 [0.86-2.28]). INTERPRETATION: The intrauterine
      environment contributes to the predisposition of women to breast cancer in
      adulthood. The in-utero mechanisms responsible for such predisposition need to be
      elucidated.

PMID- 18054880
TI  - Management of breast cancer in elderly individuals: recommendations of the
      International Society of Geriatric Oncology.
AB  - Breast cancer is the most commonly diagnosed cancer and the leading cause of
      cancer mortality in women worldwide. Elderly individuals make up a large part of
      the breast cancer population, and there are important specific considerations for
      this population. The International Society of Geriatric Oncology created a task
      force to assess the available evidence on breast cancer in elderly individuals,
      and to provide evidence-based recommendations for the diagnosis and treatment of
      breast cancer in such individuals. A review of the published work was done with
      the results of a search on Medline for English-language articles published
      between 1990 and 2007 and of abstracts from key international conferences.
      Recommendations are given on the topics of screening, surgery, radiotherapy,
      (neo)adjuvant hormone treatment and chemotherapy, and metastatic disease. Since
      large randomised trials in elderly patients with breast cancer are scarce, there
      is little level I evidence for the treatment of such patients. The available
      evidence was reviewed and synthesised to provide consensus recommendations
      regarding the care of breast cancer in older adults.

PMID- 18054881
TI  - Part II: management of resistance to imatinib in chronic myeloid leukaemia.
AB  - Updated findings from a randomised comparison of imatinib versus previous
      standard treatment in the treatment of newly diagnosed chronic myeloid leukaemia
      suggest that this first-generation tyrosine-kinase inhibitor can induce excellent
      long-term responses in most patients. However, a small proportion of patients
      will not respond or will lose previous responses, and, for these patients,
      alternative treatments are needed. This review is the second of two parts: the
      first part provided a review of the mechanisms underlying resistance to imatinib
      and this second part will discuss the management of patients who are resistant to
      imatinib by reviewing the many new drugs being introduced into clinical practice
      and suggesting strategies for decision making.

PMID- 18054882
TI  - Effects of study methods and biases on estimates of invasive breast cancer
      overdetection with mammography screening: a systematic review.
AB  - Estimates of breast-cancer overdetection, the detection with screening of cancer
      that would not have presented clinically during the woman's lifetime (and
      therefore would not be diagnosed in the absence of screening), vary widely. We
      systematically reviewed estimates of overdetection to assess the extent to which
      these might be biased by study methods. Primary research papers and reviews that
      estimated overdetection of invasive breast cancer were eligible for inclusion.
      For each paper we appraised the study design and methods to identify the extent
      and effect of bias. Two reviews and six primary studies were included. We
      categorised studies as being based on cumulative-incidence or incidence-rate
      methods. The least biased overdetection estimates range from -4% to 7.1% for
      women aged 40-49 years, 1.7% to 54% for women aged 50-59 years, and 7% to 21% for
      women aged 60-69 years. Studies consistently show that cancer overdetection
      occurs in screening for breast cancer; however, reported estimates are biased.
      Sensitivity of mammography for both cancers that will progress and for
      overdetected cancers may be increasing with time. New studies are urgently needed
      to quantify the true extent of overdetection in current mammography screening
      programmes. These studies should be designed to avoid the multiple sources of
      bias identified in this review.

PMID- 18054883
TI  - Running an ethical trial 60 years after the Nuremberg Code.
AB  - The Nuremberg Code has served as a foundation for ethical clinical research since
      its publication 60 years ago. This landmark document, developed in response to
      the horrors of human experimentation done by Nazi physicians and investigators,
      focused crucial attention on the fundamental rights of research participants and
      on the responsibilities of investigators. Although the Nuremberg Code has
      provided an important framework for discussions on the requirements of ethical
      clinical research, and has resulted in the development of other initiatives-eg,
      the Declaration of Helsinki and the Belmont Report-designed to ensure the rights
      and safety of human beings taking part in medical research, knowledge of both
      past events and the current complexity of research suggests further improvements
      are necessary in the existing approaches to human clinical research.

PMID- 18054884
TI  - A pitfall of 18-fluorodeoxyglucose-PET in a patient with a tattoo.

PMID- 18054885
TI  - Optical coherence tomography features during the evolution of serous retinal
      detachment in patients with diabetic macular edema.
AB  - PURPOSE: To characterize the evolution of serous retinal detachment (SRD)
      combined with diabetic macular edema (DME) using optical coherence tomography
      (OCT). DESIGN: Observational retrospective case series. METHODS: In our
      institution, 64 eyes of 40 diabetic patients who had SRD combined with DME were
      studied. All patients had fluorescein angiography and several OCT3 examinations
      during follow-up. Foveolar neuroretinal thickness (NRT) and SRD height were
      measured. The evolution of OCT macular profiles was qualitatively assessed.
      RESULTS: Mean follow-up was 11.8 months. DME was focal in 10 eyes (15.6%),
      diffuse in 17 (26.6%) and both diffuse and focal in 37 (57.8%). Mean initial
      decimal visual acuity (VA), NRT, and SRD height (+/- standard deviation) were
      0.35 +/- 0.21, 346.88 +/- 138.61 and 199.48 +/- 139.8 microm, respectively. SRD
      height did not correlate with VA (P = .23) or NRT (P = .31). In 13 eyes (20.3%),
      NRT above the SRD was normal. In the 19 eyes where DME improved during follow-up,
      SRD disappeared before the maximal reduction of retinal thickness in seven eyes
      (36.8%) and after or simultaneously with this reduction, in 12 eyes (63.2%).
      Among the 45 eyes where DME worsened during follow-up, SRD disappeared from 15
      eyes (33.3%). CONCLUSION: In this series, SRD height did not correlate with
      retinal thickening. The latter may appear before central neuroretinal thickening
      and disappear before or after its regression. Consequently, SRD does not seem to
      be related either to the severity of DME or to its resorption.

PMID- 18054886
TI  - Improvement of visual acuity one-year after vitreous surgery in eyes with
      residual triamcinolone acetonide at the macular hole.
AB  - PURPOSE: To investigate whether triamcinolone acetonide in the macular hole after
      surgery interferes with anatomic macular hole repair or visual acuity
      improvement. DESIGN: Prospective, interventional case series with historical
      comparison. METHODS: Pars plana vitrectomy and triamcinolone acetonide-assisted
      internal limiting membrane peeling were performed in 26 eyes (24 patients) with
      stage 3 or 4 idiopathic macular hole. The visual acuities one-year after surgery
      were compared between eyes with and without residual triamcinolone acetonide
      after surgery. RESULTS: The macular holes were closed successfully in all 26
      eyes. Nine eyes (35%) had residual triamcinolone acetonide in the macular hole at
      the end of the surgery and in the fovea on day 3 after surgery. The mean
      preoperative logarithm of the minimum angle of resolution (logMAR) visual acuity
      +/- standard deviation was 0.73 +/- 0.36 and improved significantly to 0.20 +/-
      0.29 one-year after surgery (P = .010). In the nine eyes with residual
      triamcinolone acetonide, the preoperative mean logMAR triamcinolone acetonide was
      0.81 +/- 0.33, which improved to 0.20 +/- 0.19 one-year after surgery (P = .013).
      In the remaining 17 eyes, the mean visual acuity also improved from 0.71 +/- 0.38
      before surgery to 0.21 +/- 0.28 after surgery (P = .001). No significant
      difference was found between the groups in preoperative and postoperative logMAR
      visual acuities. CONCLUSIONS: Residual triamcinolone acetonide in the macular
      hole does not interfere with anatomic or visual improvement.

PMID- 18054887
TI  - Intravenous bevacizumab causes regression of choroidal neovascularization
      secondary to diseases other than age-related macular degeneration.
AB  - PURPOSE: To investigate the safety, tolerability, and bioactivity of intravenous
      infusions of bevacizumab in patients with choroidal neovascularization (CNV)
      attributable to causes other than age-related macular degeneration. DESIGN:
      Nonrandomized clinical trial. METHODS: Ten patients with CNV received infusions
      of 5 mg/kg of bevacizumab. The primary efficacy outcome measure was change in
      visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters read at 4
      meters) at 24 weeks and secondary measures were changes from baseline in excess
      foveal thickness (center subfield thickness), area of fluorescein leakage, and
      area of CNV. RESULTS: Infusions were well tolerated and there were no ocular or
      systemic adverse events. At baseline, median VA was 25.5 letters read at 4 meters
      (20/80) and median foveal thickness was 346 mum. At the primary endpoint (24
      weeks), median VA was 48.5 letters (20/32), representing four lines of
      improvement from baseline (P = .005), median foveal thickness was 248 mum
      representing a 72% reduction in excess foveal thickness (P = .007). Four of nine
      patients had complete elimination of fluorescein leakage, three had near complete
      elimination (reductions of 91%, 88%, and 87%), two had modest reductions, and one
      had no reduction. All patients except one showed a reduction in area of CNV with
      a median reduction of 43%. CONCLUSIONS: Despite the small number of patients
      studied, the marked improvement in VA accompanied by prominent reductions in
      foveal thickness, fluorescein leakage, and area of CNV suggest a beneficial
      effect. It may be worthwhile to consider further evaluation of systemic
      bevacizumab in young patients with CNV.

PMID- 18054888
TI  - Comparison of central corneal thickness using anterior segment optical coherence
      tomography vs ultrasound pachymetry.
AB  - PURPOSE: To determine if there is a systematic difference in central corneal
      thickness (CCT) measured using anterior segment optical coherence tomography (AS
      OCT) as compared with ultrasound pachymetry. DESIGN: Prospective observational
      study. METHODS: Consecutive subjects with clinically normal corneas underwent CCT
      measurement by both ultrasound and AS-OCT while participating in a population
      based study in Ghana, West Africa. One eye of each subject was randomly selected
      for analysis. Two measurements were taken and averaged. Agreement and
      interobserver variability were also analyzed. RESULTS: One hundred and fifty-five
      subjects of African ethnicity and average age 57 years (standard deviation [SD]
      12; range, 40 to 98 years) were included. Measurements by AS-OCT and US were
      taken a mean of 15 days (maximum, six weeks) apart. The mean (SD) [range] US CCT
      was 525.3 microm (33.5) [422, 653] and 499.0 microm (32.0) [428, 613] with AS
      OCT. Measurements by the two modalities were strongly correlated (r(2) = 0.82; P
      < .001), and a significant difference was observed between mean US and AS-OCT CCT
      (SD) [range] of 26.3 microm (14.2) [-63, 12] (P < .001). The width of the limits
      of agreement was 28 microm, about 6% of the average pachymetry reading. In 50
      eyes randomly remeasured with OCT by a second observer, the intraclass
      correlation coefficient was 0.91. There was a small but significant systematic
      difference between observers (mean 6.9 microm, SD 10.9 microm), or 1.4% (P <
      .001), increasing the difference noted above. CONCLUSION: There is a reproducible
      systematic difference between CCT measurements taken with ultrasound and OCT. It
      is important to note in clinical practice, that measurements acquired by these
      two modalities are not directly interchangeable.

PMID- 18054889
TI  - Effects of antiglaucoma drugs on refractive outcomes in eyes with myopic
      regression after laser in situ keratomileusis.
AB  - PURPOSE: To assess effects of antiglaucoma drugs on refractive outcomes in eyes
      with myopic regression after laser in situ keratomileusis (LASIK). DESIGN:
      Prospective, nonrandomized clinical trial. METHODS: We examined 27 eyes with mean
      myopic regression +/- standard deviation of -1.26 +/- 0.48 diopters (D; range, 
      0.50 to -2.25 D) after LASIK. Nipradilol 2.5% was administered topically twice
      daily to these regressive eyes. We obtained the refraction (spherical equivalent,
      astigmatism), intraocular pressure (IOP) measurements, pachymetry, geometry, and
      refractive power of the cornea before and three months after treatment. RESULTS:
      Mean manifest refraction was improved significantly from -1.02 +/- 0.52 D to 
      0.44 +/- 0.39 D (P < .001). However, mean manifest astigmatism was changed from 
      0.55 +/- 0.30 D to -0.49 +/- 0.22 D, but the difference was not significant (P =
      .23). The IOP was decreased significantly from 11.4 +/- 2.4 mm Hg to 9.4 +/- 1.3
      mm Hg (P < .001). Central corneal thickness was not changed significantly from
      505.2 +/- 39.3 microm to 503.6 +/- 38.7 microm (P = .61). The posterior corneal
      surface was shifted posteriorly by 9.1 +/- 8.2 microm, and the total refractive
      power of the cornea was decreased significantly, by 0.63 +/- 0.62 D (P < .001),
      at three months after application. CONCLUSIONS: The preliminary data show that
      antiglaucoma drugs are effective for the reduction of the refractive regression,
      especially of the spherical errors, after LASIK. It is suggested that backward
      movement of the cornea may occur, possibly flattening the corneal curvature by
      lowering the IOP. Reduction of the IOP may contribute to improving regression
      after keratorefractive surgery.

PMID- 18054891
TI  - Ultrastructure and composition of basement membrane separating mature ameloblasts
      from enamel.
AB  - At a late stage of amelogenesis, a basement-membrane-like (BML) structure appears
      between mature ameloblasts and the enamel surface. Although this BML structure is
      known to contain certain basement membrane components, its detailed nature and
      role were not well defined. As such, this study examined the BML structure using
      high-resolution electron microscopy combined with immunohistochemical staining.
      Mandibular rat incisors were processed for the preparation of Epon sections for
      ultrastructural observations, and frozen sections were used for immunostaining
      laminin, heparan sulphate proteoglycan (HSPG) and type IV collagen. The BML
      structure was characterized by the presence of abundant ribbon-like 'double
      tracks', 4.5-5.0 nm wide; the form known to be taken by HSPG in basal laminae.
      The main ultrastructural component of basal laminae, known as 'cords', was
      replaced by fine filaments of type IV collagen. Immunohistochemical staining of
      the BML structure showed an intense reaction for HSPG, moderate staining for type
      IV collagen and negligible staining for laminin. These observations indicate that
      this structure is an atypical basement membrane in which the cord network is
      replaced by type IV collagen filaments. However, the BML structure was found to
      be unusually rich in HSPG, similar to kidney glomerular basement membrane. It is
      likely that this specialized basement membrane mediates firm attachment of mature
      ameloblasts to the enamel surface, and filters the influx and efflux of materials
      to and from enamel during maturation.

PMID- 18054890
TI  - Analysis of ambulatory heart failure management and its incidence on one-year
      survival.
AB  - AIM: To assess in a daily practice survey one-year survival in a cohort of
      patients with heart failure (HF) according to their clinical profiles and the way
      they were managed by cardiologists. METHODS AND RESULTS: A prospective
      observational survey was conducted in 1941 patients with HF followed up for one
      year. Results show high rates of prescription for ACE inhibitors, indicating that
      cardiologists take into account international recommendations. ACE inhibitors are
      prescribed at dosage levels approaching those recommended by the guidelines.
      However, beta-blocker prescription still shows a significant deficit and the
      prescribed doses are much lower than those currently recommended. The
      multifactorial modeling analysis showed that global heart failure (P=0.004),
      advanced NYHA class (P<0.001), renal failure (P<0.001) were predictive of poor
      outcome whereas an increased survival likelihood was observed in patients given
      ACE-inhibitor/beta-blocker combination compared with beta-blocker alone or ACE
      inhibitor alone. CONCLUSION: The results from this study should enhance the
      prescription of ACE inhibitors and beta-blockers at effective doses in compliance
      with the guidelines. They also suggest that a synergic positive effect of the
      combination of these two therapeutic classes is observed in real life situations.

PMID- 18054892
TI  - Compressive force stimulates the expression of osteogenesis-related transcription
      factors in ROS 17/2.8 cells.
AB  - OBJECTIVE: To determine how compressive force affects the expression of
      osteogenesis-related transcription factors in osteoblasts. DESIGN: Cells of ROS
      17/2.8, a typical osteoblastic cell line, were cultured with or without
      continuous compressive force (0.5-2.0 g/cm(2)). Expression of mRNA encoding the
      osteogenesis-related transcription factors Runx2, Osterix, Msx2, Dlx5 and AJ18
      was measured using real-time polymerase chain reaction. Protein expression of
      these transcription factors was determined by Western blotting. RESULTS: A
      compressive force of 1.0 g/cm(2) significantly increased mRNA and protein
      expression of Runx2, Osterix, Msx2 and Dlx5, which are critical for osteoblast
      differentiation. In contrast, mRNA and protein expression of AJ18, which
      downregulates osteoblast differentiation, were decreased with 1.0 g/cm(2) of
      compressive force. CONCLUSIONS: A compressive force of 1.0 g/cm(2), which was
      considered optimal for bone formation under the present experimental conditions,
      stimulates osteoblastic differentiation via the modulation of osteogenesis
      related transcription factors.

PMID- 18054893
TI  - Different oxidized phospholipid molecules unequally affect bilayer packing.
AB  - The aim of this study was to gain more detailed knowledge about the effect of the
      presence of defined oxidized phospholipid molecules in phospholipid bilayers.
      After chromatographic and mass spectrometry analysis, the previously used product
      of the Fenton reaction with unsaturated lecithins proved to consist of a plethora
      of oxidatively modified lecithins, useless either for the detailed study of the
      effects brought about in the bilayer or as the source of defined oxidized
      phospholipid molecules. The latter, particularly 2-(omega-carboxyacyl)- and 2-(n
      hydroperoxyacyl)-lecithins, can be more conveniently prepared by chemical or
      enzymatic synthesis rather than by chemical or physical oxidation. The effect of
      those molecules and of commercially available 12-hydroxy-stearic and
      dodecanedioic acid was studied in planar supported phospholipid bilayers (SPBs)
      by use of EPR spectrometry. The SPBs also contained 2-(5-doxylstearoyl)-lecithin
      as the spin probe, and the EPR spectral anisotropy loss, indicative of bilayer
      disordering, was measured as a function of the molar percentage of oxidized
      lipid. Most oxidized lipid molecules examined in this study were able to induce
      bilayer disordering, while hydroperoxyl group-bearing acyl chains appeared to be
      much less effective. It is concluded that the effects of different oxidized
      phospholipids on phospholipid bilayer structure cannot be generalized, as happens
      with batch-oxidized phospholipids, and that the use of defined oxidized
      phospholipid molecular species for membrane oxidative stress guarantees a more
      reliable and detailed response.

PMID- 18054894
TI  - The role of values with personal examples in altering the functions of pain:
      comparison between acceptance-based and cognitive-control-based protocols.
AB  - The purpose of the present study was twofold. First, to compare the effect of
      establishing a motivational context of values on pain tolerance, believability,
      and reported pain, with three experimental conditions: pain acceptance (ACT
      condition), pain control (CONT condition), or no values (untrained condition).
      Second, the study aimed to isolate the impact of adding the corresponding coping
      strategies to both the ACT and the CONT conditions. Thirty adults were randomly
      assigned to one of the three experimental conditions. The participants went
      through the pain task in two occasions (Test I and Test II). In Test I, the
      effects of the ACT-values protocol (which established pain as part of valued
      action), the CONT-values protocol (which established high pain as opposed to
      valued action), and the no-values protocol, were compared. In Test II, the effect
      of adding the corresponding coping strategy to each condition (defusion for ACT
      vs. suppression for CONT) was examined. Test I showed a clear superiority of the
      ACT-values protocol in increasing tolerance and lowering pain believability. In
      Test II, the superiority of the ACT protocol was replicated, while the CONT
      protocol proved useful to reduce reported pain, in accordance with previous
      studies.

PMID- 18054895
TI  - SK-126, a synthetic compound, regulates the production of inflammatory cytokines
      induced by LPS in antigen-presenting cells.
AB  - A variety of mediators released by immune cells triggers or enhances specific
      aspects of the inflammatory response. Dendritic cells (DCs) play an essential
      role in the innate immune system by shaping the adaptive immune responses and by
      controlling the production of cytokines in response to inflammatory stimuli. In
      the present study, we investigated whether SK-126, a pyridine derivative based on
      gentianine originated from a natural product, can affect the LPS-induced
      inflammatory cytokine production in DC. Interestingly, treatment of mouse bone
      marrow-derived dendritic cells (BMDCs) and the murine dendritic cell line, DC
      2.4, with SK-126 completely suppressed LPS-induced TNF-alpha expression at both
      transcriptional and protein levels. In contrast to TNF-alpha, SK-126 enhanced IL
      10 expression at both transcriptional and protein levels. To determine signaling
      pathways involved in the regulation of inflammatory cytokines, we examined the
      involvement of MAPK and the transcription factor, NF-kappaB. SK-126 enhanced
      ERK1/2 and p38 activation following LPS stimulation, but it did not induce
      phosphorylation of SAPK/JNK and NF-kappaB. Also, STAT3 phosphorylation after LPS
      stimulation was increased by SK-126 to a large extent. Using specific inhibitors,
      we confirmed that SK-126 has dual effects in which it suppresses TNF-alpha
      production and enhances IL-10 production via the up-regulation of ERK1/2 and p38.
      Finally, LPS-induced inflammatory responses such as TNF-alpha production in vivo
      were significantly reduced by treatment with SK-126. Therefore, our findings
      suggest that SK-126 may be a useful drug candidate to treat inflammatory diseases
      in which pro- or anti-inflammatory cytokines play a significant role in their
      pathogenesis.

PMID- 18054896
TI  - Communication call-evoked gamma-band activity in the auditory cortex of awake
      bats is modified by complex acoustic features.
AB  - Mustached bats emit an acoustically rich variety of calls for social
      communication. In the posterior primary auditory cortex, activity of neural
      ensembles measured as local field potentials (LFPs) can uniquely encode each call
      type. Here we report that LFPs recorded in response to calls contain oscillatory
      activity in the gamma-band frequency range (>20 Hz). The power spectrum of these
      high-frequency oscillations shows either two peaks of energy (at 40 Hz and 100
      Hz), or just one peak at 40 Hz. The relative power of gamma-band activity in the
      power spectrum of a call-evoked LFP correlates significantly with the 'harmonic
      complexity' of a call. Gamma-band activity is attenuated with reversal of
      frequency-modulated calls. Amplitude modulation, even when asymmetric across call
      reversals, has no significant effect on gamma-band activity. These results
      provide the first experimental evidence that complex features within different
      groups of species-specific calls modify the power spectrum of evoked gamma-band
      activity.

PMID- 18054897
TI  - Contribution by DRt descending facilitatory pathways to maintenance of spinal
      neuron sensitization in rats.
AB  - We investigated in different experimental rat models the potential facilitatory
      contribution of the medullary dorsal reticular nucleus (DRt) descending pathway
      to the expressions of the sensory spinal neuron sensitization such as increased
      spontaneous and noxious evoked activities, responsivity to heterotopic afferences
      stimulation and long lasting afterdischarges (ADs). We carried out experiments by
      recording from ipsilateral lumbar Wide Dynamic Range (WDR) neurons and by
      simultaneously monitoring the DRt neuron activity in neuropathic pain rats with
      chronic constriction injury of one sciatic nerve (CCI), in sham-operated and in
      "intact" rats. In particular, we recorded the spinal neuron spontaneous
      activities and the activities evoked by noxious stimulations of ipsi- and
      contralateral sciatic supplied areas before and during DRt activity blockade.
      Additionally, in "intact rats" we modulated WDR activity by iontophoretic NMDA to
      mimic CCI WDR hyperactivity without peripheral damage. We found that during DRt
      activity blockade in CCI rat neurons and in "intact" rat NMDA-treated neurons,
      the spontaneous activity was significantly reduced, the responses to
      contralateral sciatic area stimulation were reduced or suppressed, the responses
      to ipsilateral sciatic area were poorly affected (slightly reduced or
      unaffected), except for the poststimulus afterdischarges that were mostly
      suppressed. In sham-operated rats, the neuronal activity was not affected by DRt
      blockade. The finding that during the DRt nucleus blockade some expressions of
      spinal neurons sensitization, seemingly associated to sensory disorders in
      neuropathic pain, fade or extinguish designates a likely facilitatory role of DRt
      in the maintenance of neuronal sensitization and thus a contribution to
      neuropathic pain state.

PMID- 18054898
TI  - Glia maturation factor overexpression in neuroblastoma cells activates glycogen
      synthase kinase-3beta and caspase-3.
AB  - In the present study we report that a replication-defective adenovirus construct
      of GMF cDNA (GMF-V) induced overexpression of GMF protein in neuroblastoma (N18)
      cells caused cytotoxicity and loss of cell viability. A significant increase in
      activation of GSK-3beta occurred after infection with GMF-V when compared with
      mock and lacZ controls. Overexpression of GMF also increased caspase-3 activity,
      an early marker of apoptosis. Depletion of GMF gene by introducing GMF-specific
      siRNA (GsiRNA) completely blocked both activation of GSK-3beta and caspase-3
      activation whereas a control scrambled siRNA (CsiRNA) had no effect. A cell
      permeable peptide inhibitor of GSK-3beta, and lithium completely prevented GMF
      dependent activation of caspase-3. These results demonstrate that GSK-3 mediates
      activation of the death domain caspase by GMF overexpression. We also show that
      the phosphorylation of GSK-3-dependent site of Tau was a consequence of GMF
      overexpression in N18 cells. Taken together our results imply that GMF is
      involved in the signaling leading to the activation of GSK-3beta and caspase-3 in
      N18 cells and strongly suggest its involvement in neurodegeneration since GSK
      3beta is known to hyperphosphorylate tau which is associated with the
      neurotoxicity of neurofibrillary tangles in Alzheimer's disease.

PMID- 18054899
TI  - Specific AAV serotypes stably transduce primary hippocampal and cortical cultures
      with high efficiency and low toxicity.
AB  - Most current methods of gene delivery for primary cultured hippocampal neurons
      are limited by toxicity, transient expression, the use of immature neurons and/or
      low efficiency. We performed a direct comparison of seven serotypes of adeno
      associated virus (AAV) vectors for genetic manipulation of primary cultured
      neurons in vitro. Serotypes 1, 2, 7, 8 and 9 mediated highly efficient, nontoxic,
      stable long-term gene expression in cultured cortical and hippocampal neurons
      aged 0-4 weeks in vitro; serotypes 5 and 6 were associated with toxicity at high
      doses. AAV1 transduced over 90% of all cells with approximately 80% of the
      transduced cells being neurons. The method was readily adapted to a high
      throughput format to demonstrate neurotrophin-mediated neuroprotection from
      glutamate toxicity in cultured neurons at 2 weeks in vitro. These vectors should
      prove highly useful for efficient overexpression or downregulation of genes in
      primary neuronal cultures at any developmental stage.

PMID- 18054900
TI  - Task-dependent modulation of neglect dyslexia? Novel evidence from the viewing
      position effect.
AB  - Spatial neglect may involve neglect dyslexia resulting in a failure to identify
      words or parts of words in the contralesional hemispace. The present study
      explored a well-documented dissociation in neglect dyslexics' word processing,
      i.e. impaired reading aloud in the presence of good lexical decision performance
      for the same stimuli. To investigate whether this dissociation is also reflected
      in the visuo-spatial characteristics of word processing, a well-established
      paradigm of word processing in normal readers (technique of variable viewing
      positions, [Nazir, T., Heller, D., Sussmann, C., 1992. Letter visibility and word
      recognition: The optimal viewing position in printed words. Perception and
      Psychophysics, 52, 315-328]) was combined with a word naming and a lexical
      decision task. Compared to previous studies of neglect dyslexia, the present
      study additionally entailed tachistoscopical displays of word stimuli in
      different viewing positions. The word stimuli varied orthogonally along the two
      linguistic dimensions of word frequency (lexical manipulation) and syllable
      number (sublexical manipulation). Participants were sixteen patients with left
      sided visual neglect and an age-matched control group. We expected the
      dissociation in neglect dyslexia to be reflected in task-specific effects in
      naming and lexical decision. This was partly confirmed by an interaction of task
      demands with viewing-position-specific results. Interestingly these results
      pointed to a task-dependency in word processing not only in neglect patients but
      also in normal readers, when equal error rates were experimentally obtained
      between control and neglect participants. Together with the finding of a task
      specific effect of syllable number in the neglect group, the present results
      suggest that task demands modulate the degree of neglect dyslexia from early
      stages of visual word processing.

PMID- 18054901
TI  - Sexual dimorphism and steroid responsiveness of the posterodorsal medial amygdala
      in adult mice.
AB  - The posterodorsal aspect of the medial amygdala (MePD) is sexually dimorphic in
      regional volume, rostrocaudal extent, and neuronal soma size in rats. These
      dimorphisms are maintained by circulating gonadal hormones, as castration of
      adult male rats reduces MePD measures, while testosterone treatment of females
      increases them. We now report that the MePD is also sexually dimorphic in volume,
      rostrocaudal extent, and somal area in BALB/c mice. Four weeks after castration
      of adult male mice, MePD regional volume and soma size are reduced, but
      rostrocaudal extent is not, compared to sham-castrated males. Treatment of adult
      ovariectomized females with an aromatized metabolite of testosterone, estradiol,
      for 8 weeks increased MePD volume and soma size, but not rostrocaudal extent. To
      probe the possible role of afferents in the steroid-induced plasticity of the
      MePD, we examined the effect of removing the olfactory bulbs in gonadally intact
      males and in estrogen-treated females. Bulbectomy had no effect on MePD
      morphology with one exception: among gonadally intact males, neuronal soma size
      was slightly smaller in the right MePD of bulbectomized males compared to males
      with intact bulbs. These results indicate that the sexual dimorphism and hormone
      responsiveness of the MePD that has been extensively studied in rats is also
      present in mice, which offers genetic tools for future research. We detected
      little or no evidence that olfactory bulb afferents play a role in maintaining
      MePD morphology in adult mice.

PMID- 18054903
TI  - Evolutionary changes in sensory precursor formation in arthropods: embryonic
      development of leg sensilla in the spider Cupiennius salei.
AB  - We describe here for the first time the development of mechanosensory organs in a
      chelicerate, the spider Cupiennius salei. It has been shown previously that the
      number of external sense organs increases with each moult. While stage 1 larvae
      do not have any external sensory structures, stage 2 larvae show a stereotyped
      pattern of touch sensitive 'tactile hairs' on their legs. We show that these
      mechanosensory organs develop during embryogenesis. In contrast to insects,
      groups of sensory precursors are recruited from the leg epithelium, rather than
      single sensory organ progenitors. The groups increase by proliferation, and
      neural cells delaminate from the cluster, which migrate away to occupy a position
      proximal to the accessory cells of the sense organ. In addition, we describe the
      development of putative internal sense organs, which do not differentiate until
      larval stage 2. We show by RNA interference that, similar to Drosophila,
      proneural genes are responsible for the formation and subtype identity of sensory
      organs. Furthermore, we demonstrate an additional function for proneural genes in
      the coordinated invagination and migration of neural cells during sensory organ
      formation in the spider.

PMID- 18054902
TI  - Dally regulates Dpp morphogen gradient formation by stabilizing Dpp on the cell
      surface.
AB  - Decapentaplegic (Dpp), a Drosophila homologue of bone morphogenetic proteins,
      acts as a morphogen to regulate patterning along the anterior-posterior axis of
      the developing wing. Previous studies showed that Dally, a heparan sulfate
      proteoglycan, regulates both the distribution of Dpp morphogen and cellular
      responses to Dpp. However, the molecular mechanism by which Dally affects the Dpp
      morphogen gradient remains to be elucidated. Here, we characterized activity,
      stability, and gradient formation of a truncated form of Dpp (Dpp(Delta N)),
      which lacks a short domain at the N-terminus essential for its interaction with
      Dally. Dpp(Delta N) shows the same signaling activity and protein stability as
      wild-type Dpp in vitro but has a shorter half-life in vivo, suggesting that Dally
      stabilizes Dpp in the extracellular matrix. Furthermore, genetic interaction
      experiments revealed that Dally antagonizes the effect of Thickveins (Tkv; a Dpp
      type I receptor) on Dpp signaling. Given that Tkv can downregulate Dpp signaling
      by receptor-mediated endocytosis of Dpp, the ability of dally to antagonize tkv
      suggests that Dally inhibits this process. Based on these observations, we
      propose a model in which Dally regulates Dpp distribution and signaling by
      disrupting receptor-mediated internalization and degradation of the Dpp-receptor
      complex.

PMID- 18054904
TI  - Changes in mercury concentrations of segmental maternal hair during gestation and
      their correlations with other biomarkers of fetal exposure to methylmercury in
      the Japanese population.
AB  - Methylmercury (MeHg) is one of the most hazardous substances that affects the
      fetus through fish consumption. The objective of this study was to evaluate the
      changes in the level of exposure to MeHg by assessing the mercury (Hg)
      concentrations of the segmental hair at parturition and 3 months after
      parturition, and to study their correlations with the total Hg concentrations of
      maternal and cord red blood cells (RBCs) and neonatal hair as biomarkers of fetal
      exposure to MeHg at parturition. In total, 40 paired samples of maternal hair
      from the scalp, maternal and cord RBCs, and 21 samples of neonatal hair from the
      scalp were collected at parturition. In addition, 19 samples of maternal hair
      from the scalp were collected at 3 months after parturition. The maternal hair
      samples were cut into 1cm segments from the scalp end toward the tip. The
      geometric mean of the Hg concentrations in cord RBCs was approximately 1.6 times
      higher than that in the maternal RBCs, and a strong correlation coefficient
      (r=0.91) was found between them. The increase or decrease in the Hg
      concentrations of the segmental hair during gestation differed largely among
      individuals. The correlation coefficients between the Hg concentrations of the
      segmental hair and cord RBCs were the strongest (r=0.90) in the hair segment 1cm
      from the scalp and decreased gradually with the distance from the scalp. The
      correlation coefficients between the Hg concentrations of the segmental hair
      collected at 3 months after parturition and maternal RBCs were over 0.9 in the
      hair segments 5 and 6 cm from the scalp, suggesting that the time required for
      the incorporation of Hg from the blood into a growing hair was very short. The
      geometric mean of Hg concentrations in the neonatal hair at parturition was
      similar to that in the maternal hair 1cm from the scalp at parturition, and they
      exhibited a strong correlation (r=0.95). The findings of this study indicate that
      maternal hair close to the scalp at parturition and neonatal hair are useful
      biomarkers of fetal exposure to MeHg at parturition. In addition, the segmental
      maternal hair throughout gestation is essential to obtain important information
      on MeHg exposure during the different sensitive windows or bolus MeHg exposure
      during gestation.

PMID- 18054905
TI  - Factors related to dioxin and furan body levels among Michigan workers.
AB  - We evaluated serum concentrations of five selected dioxin, furan, and
      polychlorinated biphenyls (PCB) congeners among 412 workers at a Midland,
      Michigan plant that manufactured trichlorophenol and pentachlorophenol (PCP) and
      formulated chlorophenol-based products. We examined occupational indicators of
      exposure to these chlorophenols taking into account intrinsic factors such as age
      and body fat and potential environmental sources of exposure from consumption of
      local game and fish and other occupations. All five congeners were significantly
      associated with age and body fat. 2378-TCDD serum concentrations were associated
      with trichlorophenol operations, total years employed at the plant, as well as
      working as a hazardous waste worker. 123678-H(6)CDD serum concentrations were
      related to occupational PCP exposure, chloracne, recent weight loss, eating local
      game, and working as a hazardous waste worker. Serum concentrations of PCB126
      were related to smoking (inversely), and eating local fish or local game. Other
      factors such as diet and jobs outside of the chlorophenol plant exposures had
      only a very minor impact on dioxin and furan concentrations in these workers.

PMID- 18054907
TI  - alpha2B-adrenoceptor agonist ST-91 antagonizes beta2-adrenoceptor-mediated
      relaxation in rat mesenteric artery rings.
AB  - We sought an isolated vascular preparation and experimental setting where the
      function of alpha2B-adrenoceptors could be demonstrated by non-recombinant
      technique. ST-91 (2-[2,6-diethylphenylamino]-2-imidazoline), an alpha 2B
      adrenoceptor agonist with a mixed alpha adrenergic receptor type/subtype
      selection profile antagonized the relaxant effect of isoproterenol in endothelium
      denuded rat mesenteric artery rings precontracted with phenylephrine. At 10(-7) M
      of ST-91, the antagonism was characterized by a rightward shift of isoproterenol
      dose-response curve (A50=6.81+/-1.40 e-7 (n=4) vs the control 1.29+/-0.25 e-7 M
      (n=4)) with no E(max) depression. At 10(-6) M the Emax depression was prevalent
      (36.1+/-7.0% (n=4) vs the control 79.9+/-5.1% (n=4)); both actions could be
      antagonized by the alpha2-adrenoceptor antagonist yohimbine. The not subtype
      selective alpha(2)-adrenoceptor agonist xylazine (10(-7) M) did not affect the
      relaxant action of isoproterenol. Present findings are discussed in the light of
      previously reported hemodynamic effects attributed to alpha2B-adrenoceptors in
      receptor subtype-knockout animals.

PMID- 18054906
TI  - High serum PCBs are associated with elevation of serum lipids and cardiovascular
      disease in a Native American population.
AB  - We have investigated the relationships among the concentration of total serum
      polychlorinated biphenyls (PCBs), various PCB congener groupings, and three
      pesticides to total serum lipids in humans with and without self-reported
      cardiovascular disease. Blood samples were obtained from 335 adult Akwesasne
      Mohawks, and were analyzed for 101 PCB congeners, mirex, dichloro-diphenyl
      dichloro-ethylene (DDE), and hexachlorobenzene (HCB), as well as serum
      triglycerides and cholesterol. Structural equation modeling, following the
      definition of latent variables by means of confirmatory factor analysis, was used
      to analyze the relationships between serum lipids with PCBs and heart disease.
      There were significant associations among PCBs, lipids, age, and body mass index
      (BMI), a fact which justified the application of the structural equation model.
      Gender of the participant was unrelated to any of the remaining study variables.
      The results of this study are consistent with a model in which age is considered
      as both an exogenous explanatory variable and a biological driving mechanism for
      the acquisition of PCBs. Moreover, the results of this study are consistent with
      the conclusion that PCBs, acting through P450 enzymes, are directly responsible
      for increased synthesis of cholesterol and triglycerides, substances known to be
      major risk factors for cardiovascular disease.

PMID- 18054908
TI  - Analgesic activity of metabotropic glutamate receptor 1 antagonists on
      spontaneous post-operative pain in rats.
AB  - Activation of metabotropic glutamate (mGlu) receptors has previously been shown
      to play a role in inflammatory or neuropathic pain states. However, the role of
      mGlu type 1 receptors in post-operative pain remains to be investigated. In the
      present study, effects of potent and selective mGlu1 receptor antagonists A
      841720, A-794282, A-794278, and A-850002 were evaluated in a skin incision
      induced post-operative pain model in rats. Post-operative pain was examined 2 h
      following surgery using weight-bearing difference between injured and uninjured
      paws as a measure of spontaneous pain. In this model, A-841720, A-794282, A
      794278, and A-850002 induced significant attenuation of spontaneous post
      operative pain behavior, with ED50s of 10, 50, 50, and 65 micromol/kg i.p.,
      respectively. Depending on the compound, significant motor side effects were also
      observed at 3 to 10 fold higher doses. These results support the notion that
      mGlu1 receptor activation plays a significant role in nociceptive transmission in
      post-operative pain, though motor impairment may be a limiting factor in
      developing mGlu1 receptor antagonists as novel analgesics.

PMID- 18054909
TI  - Conjugated linoleic acid and cardiac health: oxidative stress and energetic
      metabolism in standard and sucrose-rich diets.
AB  - Studies on conjugated linoleic acid ingestion and its effect on cardiac tissue
      are necessary for the safe utilization of this compound as supplement for weight
      loss. Male Wistar 24-rats were divided into four groups (n=6):(C)given standard
      chow, water and 0.5 ml saline, twice a week by gavage; (C-CLA)receiving standard
      chow, water and 0.5 ml of conjugated linoleic acid, twice a week, by gavage;
      (S)given standard chow, saline by gavage, and 30% sucrose in its drinking water;
      (S-CLA)receiving standard chow, 30% sucrose in its drinking water and conjugated
      linoleic acid. After 42 days of treatment S rats had obesity with increased
      abdominal-circumference, dyslipidemia, oxidative stress and myocardial lower
      citrate synthase(CS) and higher lactate dehydrogenase(LDH) activities than C.
      Conjugated linoleic acid had no effects on morphometric parameters in C-CLA, as
      compared to C, but normalized morphometric parameters comparing S-CLA with S.
      There was a negative correlation between abdominal adiposity and resting
      metabolic rate. Conjugated linoleic acid effect, enhancing fasting-VO(2)/surface
      area, postprandial-carbohydrate oxidation and serum lipid hydroperoxide resembled
      to that of the S group. Conjugated linoleic acid induced cardiac oxidative stress
      in both fed conditions, and triacylglycerol accumulation in S-CLA rats.
      Conjugated linoleic acid depressed myocardial LDH comparing C-CLA with C, and
      beta-hydroxyacyl-coenzyme-A dehydrogenase/CS ratio, comparing S-CLA with S. In
      conclusion, dietary conjugated linoleic acid supplementation for weight loss can
      have long-term effects on cardiac health. Conjugated linoleic acid, isomers c9,
      t11 and t10, c12c9,t11" and "t10,c12" were changed to "c9, t11" and "t10, c12",
      respectively. Please check if appropriate.--> presented undesirable pro-oxidant
      effect and induced metabolic changes in cardiac tissue. Nevertheless, despite its
      effect on abdominal adiposity in sucrose-rich diet condition, conjugated linoleic
      acid may be disadvantageous because it can lead to oxidative stress and
      dyslipidemic profile.

PMID- 18054910
TI  - Doxazosin induces apoptosis of cells expressing hERG K+ channels.
AB  - The antihypertensive drug doxazosin has been associated with an increased risk
      for congestive heart failure and cardiomyocyte apoptosis. Human ether-a-go-go
      related gene (hERG) K(+) channels, previously shown to be blocked by doxazosin at
      therapeutically relevant concentrations, represent plasma membrane receptors for
      the antihypertensive drug. To elucidate the molecular basis for doxazosin
      associated pro-apoptotic effects, cell death was studied in human embryonic
      kidney cells using three independent apoptosis assays. Doxazosin specifically
      induced apoptosis in hERG-expressing HEK cells, while untransfected control
      groups were insensitive to treatment with the antihypertensive agent. An
      unexpected biological mechanism has emerged: binding of doxazosin to its novel
      membrane receptor, hERG, triggers apoptosis, possibly representing a broader
      pathophysiological mechanism in drug-induced heart failure.

PMID- 18054911
TI  - Effects of 15-deoxy-Delta12, 14 prostaglandin J2 and ciglitazone on human cancer
      cell cycle progression and death: the role of PPARgamma.
AB  - The role of PPARgamma in ciglitazone and 15-d PGJ(2)-induced apoptosis and cell
      cycle arrest of Jurkat (before and after PPARgamma gene silencing), U937 (express
      high levels of PPARgamma) and HeLa (that express very low levels of PPARgamma)
      cells was investigated. PPARgamma gene silencing, per se, induced a G2/M cell
      arrest, loss of membrane integrity and DNA fragmentation of Jurkat cells,
      indicating that PPARgamma is important for this cell survival and proliferation.
      Ciglitazone-induced apoptosis was abolished after knockdown of PPARgamma
      suggesting a PPARgamma-dependent pro-apoptotic effect. However, ciglitazone
      treatment was toxic for U937 and HeLa cells regardless of the presence of
      PPARgamma. This treatment did not change the cell cycle distribution
      corroborating with a PPARgamma-independent mechanism. On the other hand, 15-d
      PGJ(2) induced apoptosis of the three cancer cell lines regardless of the
      expression of PPARgamma. These results suggest that PPARgamma plays an important
      role for death of malignant T lymphocytes (Jurkat cells) and PPARgamma agonists
      exert their effects through PPARgamma-dependent and -independent mechanisms
      depending on the drug and the cell type.

PMID- 18054912
TI  - Elicitation of specific, Th1-biased immune response precludes skeletal muscle
      damage in cruzipain-vaccinated mice.
AB  - Cruzipain (Cz), the major cystein proteinase of Trypanosoma cruzi, is able to
      induce protective immunity against parasite challenge. However, some concern has
      arisen regarding its potential to elicit pathogenic autoimmune reactivity. To
      determine whether the adverse myopathic effects of Cz-based immunization could be
      prevented, we evaluated the co-administration of Cz with different adjuvants.
      Mice were immunized with Cz adjuvantized by alum (Cz+alum), oligodeoxynucleotides
      containing CpG motifs (Cz+ODN-CpG) or Freund's preparation (Cz+CFA). Cz triggered
      a vigorous specific humoral response, irrespective of the adjuvant used. Alum
      mainly drove response towards Th2 phenotype, characterized by specific IgG1
      antibodies and IL-10 induction, whereas Cz+ODN-CpG mice exhibited Th1-dominant
      immunity, with antibodies of the IgG2a isotype and enhanced IFN-gamma production.
      Histological examination of cardiac tissue demonstrated lesions in Cz+CFA but not
      in Cz+alum nor Cz+ODN-CpG immunized animals, suggesting that CFA is critical for
      Cz-mediated injury. Analysis of skeletal muscle revealed that mice receiving
      Cz+CFA exhibited disrupted and hyalinized myofibers, whereas [Cz+alum]-immunized
      animals showed hyalinization, architecture modifications and small inflammatory
      foci. Conversely, no abnormalities were observed in the striated muscle from the
      Cz+ODN-CpG group. Hence, generation of specific immune response skewed towards
      Th1, as that recorded for the ODN-CpG adjuvant, may preclude triggering of Cz
      mediated muscle tissue damage.

PMID- 18054913
TI  - Apoptosis in developmental and repair-related human tooth remodeling: a view from
      the inside.
AB  - Apoptosis is a key phenomenon in the regulation of the life span of odontoblasts,
      which are responsible for dentin matrix production of the teeth. The mechanism
      controlling odontoblasts loss in developing, normal, and injured human teeth is
      largely unknown. A possible correlation between apoptosis and dental pulp volume
      reduction was examined. Histomorphometric analysis was performed on intact 10 to
      14 year-old premolars to follow dentin deposition and evaluate the total number
      of odontoblasts. Apoptosis in growing healthy teeth as well as in mature
      irritated human teeth was determined using a modified TUNEL technique and an anti
      caspase-3 antibody. In intact growing teeth, the sequential rearrangement of
      odontoblasts into a multi-layer structure during tooth crown formation was
      correlated with an apoptotic wave that leads to the massive elimination of
      odontoblasts. These data suggest that apoptosis, coincident with dentin
      deposition changes, plays a role in tooth maturation and homeostasis. Massive
      apoptotic events were observed after dentin irritation. In carious and injured
      teeth, apoptosis was detected in cells surrounding the lesion sites, as well as
      in mono-nucleated cells nearby the injury. These results indicate that apoptosis
      is a part of the mechanism that regulate human dental pulp chamber remodeling
      during tooth development and pathology.

PMID- 18054914
TI  - Using continuous porous silicon gradients to study the influence of surface
      topography on the behaviour of neuroblastoma cells.
AB  - The effects of surface topography on cell behaviour are the subject of intense
      research in cell biology. These effects have so far only been studied using
      substrate surfaces of discretely different topography. In this paper, we present
      a new approach to characterise cell growth on porous silicon gradients displaying
      pore sizes from several thousands to a few nanometers. This widely applicable
      format has the potential to significantly reduce sample numbers and hence
      analysis time and cost. Our gradient format was applied here to the culture of
      neuroblastoma cells in order to determine the effects of topography on cell
      growth parameters. Cell viability, morphology, length and area were characterised
      by fluorescence and scanning electron microscopy. We observed a dramatic
      influence of changes in surface topography on the density and morphology of
      adherent neuroblastoma cells. For example, pore size regimes where cell
      attachment is strongly discouraged were identified providing cues for the design
      of low-fouling surfaces. On pore size regimes more conducive to cell attachment,
      lateral cell-cell interactions crosslinked the cell layer to the substratum
      surface, while direct substrate-cell interactions were scarce. Finally, our study
      revealed that cells were sensitive to nanoscale surface topography with feature
      sizes of <20 nm.

PMID- 18054915
TI  - Cyclophilin B induces integrin-mediated cell adhesion by a mechanism involving
      CD98-dependent activation of protein kinase C-delta and p44/42 mitogen-activated
      protein kinases.
AB  - Initially identified as a cyclosporin-A binding protein, cyclophilin B (CyPB) is
      an inflammatory mediator that induces adhesion of T lymphocytes to fibronectin,
      by a mechanism dependent on CD147 and alpha 4 beta 1 integrins. Recent findings
      have suggested that another cell membrane protein, CD98, may cooperate with CD147
      to regulate beta1 integrin functions. Based on these functional relationships, we
      examined the contribution of CD98 in the pro-adhesive activity of CyPB, by
      utilizing the responsive promonocyte cell line THP-1. We demonstrated that cross
      linking CD98 with CD98-AHN-18 antibody mimicked the responses induced by CyPB,
      i.e. homotypic aggregation, integrin-mediated adhesion to fibronectin and
      activation of p44/42 MAPK. Consistent with previous data, immunoprecipitation
      confirmed the existence of a heterocomplex wherein CD147, CD98 and beta1
      integrins were associated. We then demonstrated that CyPB-induced cell adhesion
      and p44/42 MAPK activation were dependent on the participation of
      phosphoinositide 3-kinase and subsequent activation of protein kinase C-delta.
      Finally, silencing the expression of CD98 by RNA interference potently reduced
      CyPB-induced cell responses, thus confirming the role of CD98 in the pro-adhesive
      activity of CyPB. Altogether, our results support a model whereby CyPB induces
      integrin-mediated adhesion via interaction with a multimolecular unit formed by
      the association between CD147, CD98 and beta1 integrins.

PMID- 18054916
TI  - NCX3 knockout mice exhibit increased hippocampal CA1 and CA2 neuronal damage
      compared to wild-type mice following global cerebral ischemia.
AB  - There is uncertainty as to whether the plasma membrane Na(+)/Ca(2+)exchanger
      (NCX) has a neuroprotective or neurodamaging role following cerebral ischemia. To
      address this issue we compared hippocampal neuronal injury in NCX3 knockout mice
      (Ncx3(-/-)) and wild-type mice (Ncx3(+/+)) following global cerebral ischemia.
      Using a bilateral common carotid artery occlusion (BCCAO) model of global
      ischemia we subjected NCX3 knockout and wild-type mice to 17 and 15 minutes of
      ischemia. Following the 17 minute period of ischemia, wild-type mice exhibited
      approximately 80% CA1 neuronal loss and approximately 40% CA2 neuronal loss. In
      contrast, NCX3 knockout mice displayed >95% CA1 neuronal loss and approximately
      95% CA2 neuronal loss. Following the 15 minute period of ischemia, wild-type mice
      did not exhibit any significant hippocampal neuronal loss. In contrast, NCX3
      knockout mice displayed approximately 45% CA1 neuronal loss and approximately 25%
      CA2 neuronal loss. The results clearly demonstrate that mice deficient in the
      NCX3 protein are more susceptible to global cerebral ischemia than wild-type
      mice. Our findings suggest NCX3 has a positive role in maintaining neuronal
      intracellular calcium homeostasis following ischemia, and that when exchanger
      function is compromised neurons are more susceptible to calcium deregulation and
      cell death.

PMID- 18054918
TI  - Expression profiling identifies a molecular signature of reactive astrocytes
      stimulated by cyclic AMP or proinflammatory cytokines.
AB  - Specialized glia, termed reactive astrocytes, accompany numerous pathologic
      conditions affecting the central nervous system, including stroke, multiple
      sclerosis, and neoplasia. To better define this important cell type, we employed
      high-density microarray gene expression profiling using two in vitro models of
      reactive gliosis (stimulation with dbcAMP or IL-1beta/IFNgamma). We identified 44
      differentially expressed transcripts common to both in vitro models and
      demonstrated that a subset of these genes are also differentially expressed in
      response to experimental autoimmune encephalomyelitis and focal cerebral ischemia
      in vivo. Moreover, this pattern of differential gene expression is not observed
      in hyperproliferating or neoplastic glia.

PMID- 18054917
TI  - Maladaptive effects of learning with the less-affected forelimb after focal
      cortical infarcts in rats.
AB  - It is common following stroke to focus early rehabilitation efforts on developing
      compensatory use of the less-affected body side. Here we used a rat model of
      focal cortical infarct to examine how motor skill acquisition with the less
      affected ("intact") forelimb influences sensorimotor function of the infarct
      impaired forelimb and neural activity in peri-infarct cortex. Rats proficient in
      skilled reaching with one forelimb were given focal ischemic lesions in the
      contralateral sensorimotor cortex (SMC). Recovery in this forelimb was tested
      following a period of reach training focused on the intact forelimb or control
      procedures. Quantitative measures of the cumulatively expressed transcription
      factor, FosB/DeltaFosB, were used to assay intact forelimb training effects on
      neuronal activity in remaining SMC of the infarcted hemisphere. Intact forelimb
      training worsened behavioral recovery in the impaired forelimb following
      unilateral focal ischemia. Furthermore, it decreased neuronal FosB/DeltaFosB
      expression in layer II/III of peri-infarct SMC. These effects were not found in
      sham-operated rats trained sequentially with both forelimbs or in animals
      receiving bilateral forelimb training after unilateral infarcts. Thus, focused
      use of the intact forelimb has detrimental effects on recovery of impaired
      forelimb function following a focal ischemic injury and this is linked to reduced
      neuronal activation in remaining cortex. These results suggest that peri-infarct
      cortex becomes vulnerable to early post-stroke experience with the less-affected
      forelimb and that this experience may drive neural plasticity here in a direction
      that is maladaptive for functional outcome.

PMID- 18054919
TI  - Dietary glycine does not affect physiological angiogenesis and reproductive
      function, but inhibits apoptosis in endometrial and ovarian tissue by down
      regulation of nuclear factor-kappaB.
AB  - OBJECTIVE: To study the effect of dietary glycine on female reproductive organs.
      DESIGN: Intravital microscopic, histologic, and biomolecular study. SETTING:
      Institute for Clinical & Experimental Surgery, University of Saarland. ANIMAL(S):
      Syrian golden hamsters. INTERVENTION(S): Endometrial fragments and ovarian
      follicles were transplanted into dorsal skinfold chambers of Syrian golden
      hamsters, which received glycine diet or standard pellet food (control). MAIN
      OUTCOME MEASURE(S): Angiogenesis of the grafts was analyzed during 14 days using
      intravital fluorescence microscopy. Protein expression of proliferating cell
      nuclear antigen, cleaved caspase-3, p53, and nuclear factor-kappa B (NF-kappaB)
      in the eutopic endometrium and ovary was measured by Western blot analysis.
      Fertility and reproductive function of mating hamsters was assessed. RESULT(S):
      Dietary glycine did not affect angiogenesis of endometrial and ovarian grafts, as
      indicated by a vascularized area, microvessel density, and blood perfusion
      compared with that of grafts in control animals. In addition, glycine-treated
      hamsters presented with normal reproductive function. Interestingly, glycine
      inhibited apoptosis in endometrial and ovarian tissue by down-regulation of NF
      kappaB expression. CONCLUSION(S): Our novel data indicate that glycine can be
      used as a therapeutic agent for inflammatory or angiogenic disorders without
      inducing serious side effects in the female reproductive tract.

PMID- 18054920
TI  - Spontaneous variation of leukocytospermia in asymptomatic infertile males.
AB  - OBJECTIVE: To investigate the spontaneous variation of leukocytospermia (>1
      million/mL) in semen samples from infertile men. DESIGN: Prospective cohort
      study. SETTING: Andrologic clinic at university hospital. PATIENT(S): Ninety-nine
      men evaluating for infertility causes. INTERVENTION(S): Two semen analyses
      according the World Health Organization criteria combined with urologic
      investigation without any treatment. MAIN OUTCOME MEASURE(S): Spontaneous
      (downward/upward) variation in leukocyte count, sperm concentration, total
      motility, and morphology between the two semen samples. RESULT(S): In the first
      semen analysis, 21% of men had leukocytospermia. By the second analysis,
      leukocyte concentrations were within the normal range in 9 of these 21 men,
      corresponding to a downward variation of 43%. In contrast, 7 of 78 patients with
      normal leukocyte levels at the first analysis had leukocytospermia at the second
      analysis, corresponding to an upward variation of 9%. The upward variation rates
      for sperm concentration, total motility, and morphology were 4%, 17%, and 4%,
      respectively. Downward variation rates were considerably higher for total
      motility and morphology (30% and 28%, respectively). CONCLUSION(S): The rate for
      spontaneous downward variation of leukocytospermia in the absence of treatment
      was 43% in this study. This rate should be taken into consideration when treating
      infertile men with leukocytospermia, because effective medical therapy is still
      lacking.

PMID- 18054921
TI  - Effects of progesterone on FSH-stimulated indomethacin ulcers in rats.
AB  - OBJECTIVE: To investigate whether the balance between progesterone and FSH levels
      has a role in ulcer formation/inhibition. DESIGN: Animal study. SETTING: Ataturk
      University, Faculty of Medicine, Laboratory of Pharmacology Department.
      PATIENT(S): One hundred thirty-two female Albino Wistar rats. INTERVENTION(S):
      Ovariectomy. Chronic administration of progesterone and estrogen to
      ovariectomized rats. Acute administration of progesterone to ovariectomized rats.
      Acute administration of progesterone and FSH to intact rats. Combined
      administration of mifepristone with progesterone or FSH to intact rats.
      Indomethacin administration to all rats. MAIN OUTCOME MEASURE(S): Gastric ulcer
      areas as mm(2). RESULT(S): Indomethacin-induced ulcers were significantly higher
      in ovariectomized rats than in intact rats. Chronic progesterone (1 mg/kg)
      inhibited gastrointestinal system ulcers by 51.2%, whereas 2 and 5 mg/kg chronic
      progesterone and 1, 2, and 5 mg/kg chronic estrogen were not effective. Acute
      progesterone (5 mg/kg) increased indomethacin ulcers significantly in
      ovariectomized rats. FSH increased indomethacin ulcers significantly. In
      addition, progesterone increased indomethacin ulcers significantly in intact
      rats. Mifepristone antagonized the ulcerogenic effects of FSH and progesterone.
      CONCLUSION(S): Our data suggest that progesterone is not an antiulcer hormone,
      and produces ulcers via its own receptor. In addition, FSH may produce
      ulcerogenic effects via progesterone receptors. The low doses of progesterone
      (inhibits endogenous FSH) cannot stimulate its own receptors sufficiently for
      ulcer formation and prevent the ulcerogenic effects of FSH by decreasing FSH
      concentration.

PMID- 18054922
TI  - Dislodged Essure microinsert.
AB  - A woman presented with symptoms of vaginal bleeding and pelvic pain shortly after
      hysteroscopic sterilization. Sonographic and hysteroscopic images of a dislodged
      Essure microinsert (Conceptus Inc., San Carlos, CA) are provided.

PMID- 18054923
TI  - Polycystic ovary syndrome is related to idiopathic intracranial hypertension
      according to magnetic resonance imaging and magnetic resonance venography.
AB  - Magnetic resonance imaging and magnetic resonance venography findings of 30 women
      with polycystic ovary syndrome and headache were studied prospectively. Our
      magnetic resonance imaging and magnetic resonance venography findings support
      that polycystic ovary syndrome with severe headache is a promoter of idiopathic
      intracranial hypertension.

PMID- 18054924
TI  - Reduced expression of 14-3-3 gamma in uterine leiomyoma as identified by
      proteomics.
AB  - OBJECTIVE: To use proteomic techniques, including two-dimensional electrophoresis
      (2DE), Western blot, and mass spectrometry, to screen and identify proteins that
      were expressed differently in patients with uterine leiomyoma versus normal
      myometrium. DESIGN: First, identify proteins important for leiomyogenesis by
      comparing protein expression in leiomyoma and normal myometrium. Second, examine
      the expression level of selected proteins on a larger panel of leiomyomas.
      SETTING: Academic research laboratory. PATIENT(S): Consenting premenopausal
      patients scheduled to undergo hysterectomy for symptomatic uterine leiomyomas.
      INTERVENTION(S): Paired samples of leiomyoma and adjacent myometrium were
      obtained and submitted to 2DE, mass spectrometry, Western blot, reverse
      transcription polymerase chain reaction (RT-PCR), and immunohistochemistry. MAIN
      OUTCOME MEASURE(S): Protein expression. RESULT(S): A comparison of protein
      patterns revealed 37 protein spots significantly changed, with 10 protein spots
      with concordantly increased and 27 protein spots with concordantly decreased
      intensity in leiomyoma compared with normal myometrium. Ten of these proteins
      were identified by tandem mass spectrometry. Interestingly, one of the proteins,
      which exhibited a marked down-regulation in leiomyoma tissues, was the recently
      identified highly conserved cellular protein 14-3-3-gamma. The reduction of the
      14-3-3 gamma in leiomyoma tissues was confirmed by comparative immunoblotting (n
      = 25) and RT-PCR (n = 25) as well as by immunohistochemistry (n = 35) of
      individual-matched neoplastic and normal myometrium tissue specimens.
      CONCLUSION(S): The consistency of 14-3-3 gamma reduction in uterine leiomyoma
      suggests that 14-3-3 protein may play a role in the origin or growth of
      leiomyoma.

PMID- 18054925
TI  - Effect of gold nanoparticles on spermatozoa: the first world report.
AB  - OBJECTIVE: To evaluate the spermatotoxicity of gold nanoparticles. DESIGN:
      Experimental study. SETTING: A university in Thailand. PATIENT(S): Single-donor
      fresh semen sample. INTERVENTION(S): A mixture of gold nanoparticle solution and
      semen was prepared and further analyzed. MAIN OUTCOME MEASURE(S): Spermatozoa
      appearance. RESULT(S): After mixing the semen with a gold nanoparticle solution,
      25% of sperm were not motile. Penetration of gold nanoparticle into the sperm
      heads and tails was observed. CONCLUSION(S): Spermatotoxicity of the gold
      nanoparticle can be detected.

PMID- 18054926
TI  - Robot-assisted laparoscopic trachelectomy after supracervical hysterectomy.
AB  - OBJECTIVE: To present a case of successful robotic assisted laparoscopic
      trachelectomy. DESIGN: Case report. SETTING: Tertiary care facility. PATIENT(S):
      A 40-year-old female with history of severe endometriosis and adhesions presented
      with persistent pain and bleeding after abdominal supracervical hysterectomy
      after failed attempt for laparoscopic-assisted vaginal hysterectomy and total
      abdominal hysterectomy. INTERVENTION(S): Robot-assisted laparoscopic
      trachelectomy and treatment of associated pelvic disease. MAIN OUTCOME
      MEASURE(S): Successful completion of robot-assisted trachelectomy. RESULT(S):
      There were no intraoperative or postoperative complications and minimal blood
      loss. At 10 months' follow-up the patient was doing well with resolution of her
      symptoms. CONCLUSION(S): Robotic surgery may bridge the gap between laparotomy
      and laparoscopy for trachelectomy in complicated cases.

PMID- 18054927
TI  - Local lymphocytic and epithelial activation in a case of autoimmune oophoritis.
AB  - OBJECTIVE: To further define the immunological tissular modifications in
      premature ovarian failure (POF). METHOD: The patient was followed up for
      premature ovarian failure and mild endometriosis associated with serum
      antiovarian antibodies. A laparoscopic ovarian biopsy was decided on to analyze
      the tissue and support the onset of immunosuppressive therapy.
      Immunohistochemistry was performed using monoclonal antibodies directed against T
      cell membrane markers, as well as activation molecules, to define the composition
      of the cellular infiltrate and the consequences on ovarian tissue. RESULT(S): A
      dense infiltration of activated T lymphocytes was observed in close contact with
      follicular epithelium expressing HLA-DR and CD40. CONCLUSION(S): This observation
      supports the role of cellular immunity in ovarian autoimmunity with features very
      similar to those reported in murine models and other human autoimmune endocrine
      pathologies.

PMID- 18054928
TI  - Propecia-induced spermatogenic failure: a report of two cases.
AB  - OBJECTIVE: To describe the results of two cases of azoospermia and severe
      oligospermia in men during and after cessation of finasteride 1 mg. DESIGN: Case
      report. SETTING: Tertiary-care hospital-based clinic for andrology/male
      infertility. PATIENT(S): Two patients with azoospermia and severe oligospermia
      using finasteride 1 mg for hair loss. INTERVENTION(S): Discontinuation of
      finasteride. MAIN OUTCOME MEASURE(S): Improvement in sperm concentration.
      RESULT(S): Patient A had documented azoospermia over 1 year and was initially
      booked for a testicular biopsy. Six months after discontinuation of finasteride 1
      mg daily he showed improvement in sperm concentration to 5.5 x 10(6)/mL. Patient
      B had severe oligospermia with a sperm concentration of 4 x 10(6)/mL. Sperm
      concentration improved to 6.6 then 18.7 x 10(6)/mL at 3 and 6 months after
      stopping finasteride. CONCLUSION(S): We report two cases of infertile patients
      with azoospermia or severe oligospermia who showed significant improvements in
      sperm concentrations 6 months after the discontinuation of finasteride. In one
      case, improvement in semen parameters prevented the need for testicular biopsy
      and corrected the azoospermia. Stopping finasteride in the infertility population
      may improve semen parameters, and may allow for less invasive fertility
      treatments.

PMID- 18054929
TI  - Increased insulin-like growth factor-1 after oophorectomy in postmenopausal
      women.
AB  - IGF-1 levels increased, and IGF-2 and IGFBP-3 levels remained unchanged, in
      postmenopausal women following oophorectomy. The increase in IGF-1 likely results
      from decreased ovarian steroidogenic precursors resulting from removal of the
      hormonally active ovary. This finding raises concerns, given the association
      between increased IGF-1 and elevated colon cancer risk, and adds to the
      literature suggesting a potential benefit from ovarian preservation.

PMID- 18054930
TI  - Use of luteal estrogen supplementation in normal responder patients treated with
      fixed multidose GnRH antagonist: a prospective randomized controlled study.
AB  - To evaluate the effect of luteal estrogen supplementation on pregnancy rates in
      normal responder IVF patients treated with recombinant FSH and fixed multidose
      GnRH antagonist, patients were randomized into two groups to receive vaginal 600
      mg/d micronized progesterone for luteal phase supplementation with or without
      transdermal estrogen supplementation (100 microg/d). Because pregnancy rates and
      ongoing pregnancy rates were similar with and without estrogen supplementation
      (50.0% vs. 55.2% and 36.6% vs. 34.4%, respectively), we concluded that luteal
      estrogen supplementation in fixed multidose GnRH antagonist cycles did not change
      the pregnancy rates significantly.

PMID- 18054931
TI  - Effect of the oxytocin antagonist antocin and agonist decomoton on baboon luteal
      cell production and release of progesterone.
AB  - OBJECTIVE: To evaluate the effect of oxytocin, its antagonist antocin, and
      agonist decomoton on baboon luteal cell P secretion. DESIGN: Prospective study.
      SETTING: Academic department of obstetrics and gynecology in a US medical school.
      ANIMAL(S): Luteal-phased timed corpora lutea (CL) from a cohort of adult cycling
      baboons (Papio anubis). INTERVENTION(S): Dispersed luteal cells from luteal phase
      baboon CL were cultured and treated with nothing (control), oxytocin (4-400 mU),
      antocin (4-400 microg), oxytocin with antocin, decomoton (4-400 microg), or
      oxytocin with decomoton. MAIN OUTCOME MEASURE(S): Basal and hCG (10 U)-stimulated
      P were measured in the incubate. RESULT(S): Basal P secretion did not change
      significantly with all peptides studied. The hCG-stimulated P secretion was
      significantly inhibited by oxytocin (4-400 mU), antocin (4-400 microg), and
      antocin combined with oxytocin, and with oxytocin, decomoton, and decomoton
      combined with oxytocin. Antocin (-12%) was less inhibitory than oxytocin (-25% to
      -22%). Antocin combined with oxytocin enhanced the inhibition to -35% to -39%.
      Decomoton had stronger (not significant) inhibition than oxytocin. Mean
      inhibition was 28%-35% with all doses of oxytocin, decomoton, or combined
      together. CONCLUSION(S): Although decomoton, an oxytocin agonist inhibited hCG
      stimulated luteal cell P secretion in vitro, antocin also acted like an agonist,
      rather than an antagonist, in inhibiting P secretion.

PMID- 18054932
TI  - Effectiveness of cetrorelix for the prevention of premature luteinizing hormone
      surge during controlled ovarian stimulation using letrozole and gonadotropins: a
      randomized trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a GnRH antagonist in preventing
      premature LH surge under a letrozole and gonadotropin protocol. DESIGN:
      Prospective, randomized clinical trial. SETTING: A teaching hospital and tertiary
      medical center. PATIENT(S): Sixty-one patients were randomly assigned into two
      letrozole and gonadotropin-treated groups. These were distinguished by the
      absence (group I) or presence (group II) of supplementation with 0.25 mg of
      cetrorelix. INTERVENTION(S): Controlled ovarian stimulation with letrozole and
      gonadotropins, cetrorelix and intrauterine insemination. MAIN OUTCOME MEASURE(S):
      Rate of premature LH surge. RESULT(S): Compared with group I, the rate of
      premature LH surge was statistically significantly lower for group II (43.4%
      [13/30] vs. 19.4% [6/31]), but the amount of gonadotropins used was statistically
      significantly higher (817.5 +/- 28.5 vs. 907.5 +/- 27.3 IU). Patients with
      premature LH surge had a statistically significantly lower pregnancy rate (21.4%
      [9/42] vs. 0 [0/18]) relative to their unaffected counterparts. CONCLUSION(S): A
      flexible protocol of 0.25 mg of cetrorelix for IUI cycles appears to suppress the
      rate of premature LH surge during ovarian stimulation with letrozole and
      gonadotropins. However, the incidence of premature LH surge remains too high, and
      modification will be necessary before the application of cetrorelix to IVF
      treatment.

PMID- 18054933
TI  - Systemic methotrexate to treat ectopic pregnancy does not affect ovarian reserve.
AB  - OBJECTIVE: To evaluate whether methotrexate (MTX) compromises ovarian reserve and
      future reproductive outcome in women undergoing assisted reproductive technology
      (ART), when it is used as first-line treatment for ectopic pregnancy (EP).
      DESIGN: Prospective, observational study. SETTING: University-affiliated private
      IVF unit. PATIENT(S): Twenty-five women undergoing IVF-ICSI who were treated with
      MTX (1 mg/kg IM) for an EP after ART. INTERVENTION(S): Evaluation of reproductive
      outcome and serum anti-Mullerian hormone (AMH) levels. Serum AMH was evaluated
      before administering MTX and >or=1 week after the resolution of the EP.
      Reproductive outcome was evaluated by comparing subsequent IVF-ICSI cycles after
      EP resolution. MAIN OUTCOME MEASURE(S): Serum AMH levels, cycle length,
      gonadotropin dose required, peak serum E(2) level, oocytes collected, and embryos
      obtained. RESULT(S): Serum AMH levels before MTX were not statistically
      significantly different from those after treatment (3.7 +/- 0.3 ng/mL vs. 3.9 +/-
      0.3 ng/mL). Patients undergoing a subsequent cycle after systemic treatment for
      EP had similar cycle durations (10.3 vs. 10.8 d), gonadotropin requirements
      (2,775 vs. 2,630.3 IU), peak E(2) levels (1,884.3 vs. 1,523.6 pg/mL), number of
      oocytes retrieved (12.1 vs. 10.5), and total number of embryos obtained (7.1 vs.
      6.5). CONCLUSION(S): Single-dose MTX is a safe first-treatment choice that does
      not compromise future reproductive outcomes in women who are diagnosed with EP
      after ART.

PMID- 18054934
TI  - Low-dose acetylsalicylic acid plus prednisolone as an adjuvant treatment in IVF:
      a prospective, randomized study.
AB  - OBJECTIVE: To test whether adjuvant therapy with acetylsalicylic acid (ASA) and
      prednisolone (ASA+Pred) could improve the outcome of IVF in good-pregnancy
      prognosis patients. DESIGN: Prospective, randomized study. SETTING: University
      hospital. PATIENT(S): Three hundred ninety-five infertile couples undergoing IVF.
      INTERVENTION(S): Patients were randomized to receive ASA+Pred (n = 97) or nothing
      (n = 298), in addition to the routinely used IVF medications. MAIN OUTCOME
      MEASURE(S): The primary endpoint was implantation rate (IR). Secondary endpoints
      were number of retrieved oocytes and pregnancy rate (PR). The blood flow in
      uterine arteries and subendometrial vessels also was measured. RESULT(S):
      Patients who received ASA+Pred had significantly more retrieved oocytes. The PR
      and IR in the study group and in controls were 50.5% and 40.6% and 25.1% and
      19.4%, respectively, values that were not significantly different from one
      another. Uterine blood flows were not significantly different between treated and
      nontreated patients. A statistically significantly lower incidence of severe
      ovarian hyperstimulation syndrome was noted among treated patients who were at
      high risk of developing ovarian hyperstimulation syndrome (1.7% vs. 6.5%).
      CONCLUSION(S): Adjuvant treatment with ASA+Pred improves ovarian responsiveness
      but does not significantly improve uterine blood fluxes, PR, and IR. It may be
      effective in preventing the onset of severe ovarian hyperstimulation syndrome.

PMID- 18054935
TI  - Involvement of vascular endothelial growth factor on spermatogenesis in testis
      with varicocele.
AB  - The expression and the role of vascular endothelial growth factor in human testes
      with varicocele were examined. Vascular endothelial growth factor expression was
      increased in testes with varicocele, and was inversely correlated with total
      motile sperm count and testicular volume, indicating that excessive vascular
      endothelial growth factor has harmful effects on spermatogenesis in testes with
      varicocele.

PMID- 18054936
TI  - Molecular epidemiology of Cryptosporidium in humans and cattle in The
      Netherlands.
AB  - The protozoan parasite Cryptosporidium is found world-wide and can cause disease
      in both humans and animals. To study the zoonotic potential of Cryptosporidium in
      The Netherlands we isolated this parasite from the faeces of infected humans and
      cattle and genotyped those isolates for several different markers. The overall
      genotyping results showed: for humans isolates, 70% Cryptosporidium hominis, 19%
      Cryptosporidium parvum, 10% a combination of C. hominis and C. parvum, and 1%
      Cryptosporidium felis; and for cattle isolates 100% C. parvum. Analysis of the
      genetic variants detected for the HSP70, ML1 and GP60 markers showed: for human
      isolates, one C. hominis and two C. parvum variants (C. parvum and C. parvum NL)
      for HSP70, one C. hominis and five C. parvum variants (C1, C2, C3, and C2 NL1 and
      C2 NL2) for ML1, four C. hominis (mainly IbA10G2) and four C. parvum variants
      (mainly IIaA15G2R1) for GP60; and the cattle isolates only C. parvum (not C.
      parvum NL1) for HSP70, C1 and C2 for ML1, and 17 different IIa sub-types (mainly
      IIaA15G2R1) for GP60. Molecular epidemiological analysis of the human data showed
      a C. hominis peak in autumn. The majority (80%) of the human cases were children
      aged between 0 and 9 years and >70% of these were caused by C. hominis. Patients
      >25 years of age were infected mainly with C. parvum. We conclude that C. hominis
      IbA10G2 is found at high frequencies in autumn in humans and not in cattle. The
      high prevalence of C. parvum IIaA15G2R1 in both humans and cattle indicates that
      cattle may be a reservoir for this sub-type in The Netherlands.

PMID- 18054937
TI  - Consumption of omega-3 fatty acids is not associated with a reduction in carotid
      atherosclerosis: the Genetics of Coronary Artery Disease in Alaska Natives study.
AB  - OBJECTIVE: This study was designed to evaluate the relation between omega-3 fatty
      acid (FA) consumption and atherosclerosis. BACKGROUND: The hypothesis that omega
      3 FAs protect against atherosclerosis has not been tested with objective measures
      of atherosclerosis. METHODS: A population-based sample of 1131 Alaskan Eskimos of
      age >or=18 underwent ultrasound assessment of carotid atherosclerosis. Those of
      age >35 (N=686) were included in the analysis. Diet was assessed by a food
      frequency questionnaire. Intimal-medial thickness (IMT) of the far wall of the
      distal common carotid arteries and plaque score (number of segments containing
      plaque) were assessed. RESULTS: Mean consumption of total omega-3 FAs was 4.76
      g/day in those without and 5.07 g/day in those with plaque. In models adjusting
      for relevant risk factors, presence and extent of plaque were unrelated to intake
      of C20-22 omega-3 FAs or total omega-3 FAs. In contrast, the odds of plaque rose
      significantly with quartiles of palmitic (p=0.02) and stearic acid intake
      (p=0.04). The extent of plaque (or plaque score) was also associated with a
      higher percentage intake of palmitic acid (p=0.01). IMT was negatively associated
      with grams of C20-22 omega-3 FAs (p=0.05), total omega-3 (p=0.05), palmitate
      (p=0.03), and stearate (p=0.03) consumed. CONCLUSIONS: Dietary intake of omega-3
      FAs in a moderate-to-high range does not appear to be associated with reduced
      plaque, but is negatively associated with IMT. The presence and extent of carotid
      atherosclerosis among Eskimos is higher with increasing consumption of saturated
      FAs.

PMID- 18054938
TI  - Endothelial cells are protected against phagocyte-transmitted Chlamydophila
      pneumoniae infections by laminar shear stress Gueinzius: Shear stress protects
      from C. pneumoniae infection.
AB  - The respiratory pathogen Chlamydophila pneumoniae can be detected in
      atherosclerotic vessels, but the mechanism of dissemination from lung to
      vasculature remains unknown. Disturbance of vascular shear stress is a risk
      factor for atherosclerosis. We investigated whether polymorphonuclear neutrophils
      (PMN) might serve as carriers, transmitting C. pneumoniae to endothelial cells
      and how this is affected by shear stress. PMN were prepared from blood and
      incubated with C. pneumoniae. Real-time PCR and Pathfinder staining showed that
      after 1h, 20% of C. pneumoniae were ingested and started to form inclusions. When
      infected PMN were co-incubated with HUVEC for 96h, 10% of PMN-ingested C.
      pneumoniae were transmitted to HUVEC as shown by PCR and confocal microscopy.
      Infection of HEp-2 cells with C. pneumoniae harvested from HUVEC resulted in C.
      pneumoniae replication and confirmed that the bacteria remained infective.
      Exposure to laminar shear stress in a rotating cone-and-plate apparatus did not
      affect the transmission of C. pneumoniae from PMN to HUVEC, but led to a 75%
      reduction of inclusion formation. This can explain the focal distribution of C.
      pneumoniae in the vasculature and links two risk factors of atherosclerosis, i.e.
      the lack of laminar flow and infection.

PMID- 18054939
TI  - Neuropeptide Y signal peptide Pro7 substitution protects against coronary artery
      atherosclerosis: the Helsinki Sudden Death Study.
AB  - OBJECTIVE: Neuropeptide Y (NPY) has a single nucleotide polymorphism at T1128C,
      leading to change of Leucine7 to Proline7. The Leu7Pro substitution has been
      linked to cardiovascular disease, but it is unknown whether the Pro7 allele is
      associated with increased or decreased risk of coronary heart disease (CHD). The
      aim of the present study was to investigate the association of the Leu7Pro
      polymorphism with coronary atherosclerosis and its consequences. METHODS: We
      studied two autopsy series comprising 700 unselected middle-aged Caucasian men
      (Helsinki Sudden Death Study) who had died suddenly out of hospital. Areas of
      coronary artery atherosclerosis, narrowings of coronary arteries, and presence of
      myocardial infarction and/or coronary thrombosis were analyzed. All information
      including CHD risk factor data was obtained from 410 men. RESULTS: NPY genotype
      distribution was Leu7/Leu7=89.8%, Leu7/Pro7=10.0% and Pro7/Pro7=0.2%). Although
      the Pro7 allele was associated with reported hypertension (p=0.03), the men
      carrying Pro7 allele had lower area of fatty streaks (p=0.04), fibrotic lesions
      (p=0.07) and complicated lesions (p=0.004) in the left anterior descending (LAD)
      coronary artery and also less severe LAD narrowings (p=0.04) than men with the
      Leu7/Leu7 genotype. Supporting a protective role for the Pro7 allele against
      atherosclerosis, only 1 out of 46 men (2%) with coronary thrombosis carried the
      Pro7 allele (p=0.08 compared to men dying of other causes). This association
      weakened (OR 0.18 for Pro7 versus Leu7/Leu7, p=0.16) when adjusted for all
      available CHD risk factors. CONCLUSIONS: NPY Pro7 substitution protects middle
      aged men from coronary artery atherosclerosis and might decrease the risk of
      acute coronary events.

PMID- 18054940
TI  - Association of ischemia-modified albumin and melatonin in patients with ST
      elevation myocardial infarction.
AB  - INTRODUCTION: It has been proposed that reactive oxygen species (ROS) generated
      during myocardial ischemia-reperfusion modify the N-terminus of serum albumin
      resulting in ischemia-modified albumin (IMA) formation. Likewise, several recent
      publications provide evidence that melatonin, a circadian endogenously produced
      indolamine, is a direct scavenger of ROS. We sought to investigate the
      relationship between IMA and melatonin in ST- elevation myocardial infarction
      (STEMI). METHODS: We compared IMA and melatonin levels in 27 patients with STEMI
      undergoing primary angioplasty and 20 age- and gender-matched healthy normal
      subjects. Blood samples were drawn at 02:00h (night period) and 09:00h (day
      period) while patients were resting, to assess IMA and melatonin. RESULTS: In
      both groups, melatonin concentrations maintained a diurnal variation, but the
      difference between nocturnal and diurnal levels was less in the STEMI-patients
      than in the control group (p<0.001). In contrast to findings about melatonin, IMA
      levels showed no diurnal variations in control subjects. However, the STEMI group
      showed a diurnal fluctuation with significantly higher levels at 02:00h (p<0.01).
      The association between IMA and melatonin remained statistically significant
      after adjustment for cardiovascular risk factors. An inverse correlation between
      IMA and melatonin at 02:00h and at 09:00h was observed, with respective r-values
      of -0.42 (p<0.03) and -0.57 (p<0.002). CONCLUSIONS: Circulating IMA is negatively
      correlated to melatonin in STEMI-patients. Our results suggest that melatonin
      might exert a beneficial effect as a radical scavenger in a human model of
      myocardial ischemia-reperfusion.

PMID- 18054941
TI  - HIV infection and high density lipoprotein metabolism.
AB  - HIV infection and its treatment are associated with dyslipidemia, including
      hypoalphalipoproteinemia, and increased risk of cardiovascular disease.
      Parameters of HDL metabolism in HIV-positive patients were investigated in a
      cross-sectional study. The following groups of subjects were selected: (i) 25
      treatment-naive HIV-infected patients or HIV-infected patients on long therapy
      break, (ii) 28 HIV-infected patients currently treated with protease inhibitors,
      and (iii) 33 HIV-negative subjects. Compared to the HIV-negative group, all
      groups of HIV-infected patients were characterized by significantly elevated
      triglyceride and apolipoprotein B levels, mass and activity of lecithin
      cholesterol acyl transferase and cholesteryl ester transfer protein (p<0.01).
      Total and LDL cholesterol was lower in treatment-naive HIV-infected group only.
      HDL cholesterol and prebeta(1)-HDL were significantly lower in all HIV-infected
      groups (p<0.05), while mean levels of apolipoprotein A-I (apoA-I) and ability of
      plasma to promote cholesterol efflux were similar in all groups. We found a
      positive correlation between apoA-I and levels of CD4+ cells (r(2)=0.3, p<0.001).
      Plasma level of phospholipid transfer protein was reduced in the group on
      antiretroviral therapy. Taken together these results suggest that HIV infection
      is associated with modified HDL metabolism re-directing cholesterol to the apoB
      containing lipoproteins and likely reducing the functionality of reverse
      cholesterol transport.

PMID- 18054943
TI  - Co-activation alters the linear versus non-linear impression of the EMG-torque
      relationship of trunk muscles.
AB  - The use of electromyographic signals in the modeling of muscle forces and joint
      loads requires an assumption of the relationship between EMG and muscle force.
      This relationship has been studied for the trunk musculature and been shown to be
      predominantly non-linear, with more EMG producing less torque output at higher
      levels of activation. However, agonist-antagonist muscle co-activation is often
      substantial during trunk exertions, yet has not been adequately accounted for in
      determining such relationships. The purpose of this study was to revisit the EMG
      moment relationship of the trunk recognizing the additional moment requirements
      necessitated due to antagonist muscle activity. Eight participants generated a
      series of isometric ramped trunk flexor and extensor moment contractions. EMG was
      recorded from 14 torso muscles, and the externally resisted moment was
      calculated. Agonist muscle moments (either flexor or extensor) were estimated
      from an anatomically detailed biomechanical model of the spine and fit to: the
      externally calculated moment alone; the externally calculated moment combined
      with the antagonist muscle moment. When antagonist activity was ignored, the EMG
      moment relationship was found to be non-linear, similar to previous work.
      However, when accounting for the additional muscle torque generated by the
      antagonist muscle groups, the relationships became, in three of the four
      conditions, more linear. Therefore, it was concluded that antagonist muscle co
      activation must be included when determining the EMG-moment relationship of trunk
      muscles and that previous impressions of non-linear EMG-force relationships
      should be revisited.

PMID- 18054942
TI  - Effect of pioglitazone on progression of subclinical atherosclerosis in non
      diabetic premenopausal Hispanic women with prior gestational diabetes.
AB  - The Pioglitazone in the Prevention of Diabetes (PIPOD) study was a single arm 3
      year open-label pioglitazone treatment to determine the effects of pioglitazone
      in women with prior gestational diabetes mellitus (GDM) who had completed the
      troglitazone in the Prevention of Diabetes (TRIPOD) study. Here we report the
      results on progression of subclinical atherosclerosis, measured by carotid intima
      media thickness (CIMT) in non-diabetic women. Data were analyzed to compare CIMT
      progression rates during pioglitazone treatment to rates that had been observed
      during either placebo or troglitazone treatment in the TRIPOD study. Sixty-one
      women met the entry criteria with mean age of 40 years. In the 30 women who came
      to PIPOD from the placebo arm of TRIPOD, the CIMT rate was 69% lower during
      pioglitazone treatment than it had been during placebo (0.0031 vs. 0.0100mm/yr,
      p=0.006). In the 31 women who came to PIPOD from the troglitazone arm of TRIPOD,
      CIMT rate was 38% lower during pioglitazone than it had been during troglitazone,
      a difference that was not statistically significant (0.0037 vs. 0.0060mm/year;
      p=0.26). Adjustment for differences in baseline characteristics and potential on
      trial confounders did not alter the conclusion but did increase the CIMT rates
      differences slightly. We conclude that treatment with pioglitazone slowed CIMT
      progression in women who had been on placebo in the TRIPOD study and maintained a
      relatively low rate of progression in women who had been on troglitazone.
      Pioglitazone slows progression of subclinical atherosclerosis in young Hispanic
      women at increased risk for type 2 diabetes.

PMID- 18054944
TI  - Preparative isolation of procyanidins from grape seed extracts by high-speed
      counter-current chromatography.
AB  - High-speed counter-current chromatography (HSCCC) has been applied to the
      separation of grape seed procyanidins. The isolation of dimeric to tetrameric
      procyanidins is achieved after removing the polymeric compounds by solvent
      precipitation. An additional clean-up by solid-phase extraction on polyamide
      improved the purities of the isolated compounds. The solvent systems ethyl
      acetate/2-propanol/water (40:1:40, v/v/v), ethyl acetate/2-propanol/water
      (20:1:20, v/v/v), and ethyl acetate/1-butanol/water (14:1:15, v/v/v) were
      successfully used for the fractionation. The combination of HPLC-MS, diode array
      detection, and NMR analysis, as well as phloroglucinolysis, confirmed the
      structures of the isolated compounds: B1 [EC-(4beta-->8)-C], B2 [EC-(4beta-->8)
      EC], B3 [C-(4alpha-->8)-C], B4 [C-(4alpha-->8)-EC], B5 [EC-4beta-->6-EC], B7 [EC
      (4beta-->8)-C], [ECG-(4beta-->8)-C], trimeric procyanidin C1 [EC-4beta-->8-EC
      4beta-->8-EC], and the tetrameric procyanidin cinnamtannin A2 (where C: catechin,
      EC: epicatechin and ECG: epicatechin-3-O-gallate).

PMID- 18054946
TI  - Performance evaluation of evaporative light scattering detection and charged
      aerosol detection in reversed phase liquid chromatography.
AB  - In pharmaceutical industry ultraviolet (UV) detection is often used as the
      preferred detection technique in HPLC analysis since most pharmaceutical
      compounds possess a UV-absorbing chromophore. However, in case the active
      pharmaceutical ingredient (API) does not have a UV-absorbing chromophore, or if
      some of the impurities present lack a chromophore, they will not be detected in
      routine HPLC analysis employing only a UV detector and alternative detection
      schemes have to be used. Refractive index detection or mass spectroscopy (MS) can
      be used but these detectors have their intrinsic weaknesses, such as lack of
      sensitivity or high cost. With the appearance of semi-universal techniques such
      as evaporative light scattering detection (ELSD), and more recent, charged
      aerosol detection (CAD), detection of non-UV-absorbing compounds became feasible
      without having to resort to such complex or costly detection methods. This paper
      evaluates the different performance characteristics such as sensitivity,
      linearity, accuracy and precision of both the ELSD and CAD detector coupled to
      HPLC. One disadvantage of this type of detector is the non-linear response
      behaviour which makes direct linear regression for making calibration curves
      inaccurate.

PMID- 18054945
TI  - Quantitative determination of drug encapsulation in poly(lactic acid)
      nanoparticles by capillary electrophoresis.
AB  - Capillary electrophoretic (CE) methods were used for the quantitative
      determination of model drugs [salbutamol sulphate (SS), sodium cromoglycate (SCG)
      and beclomethasone dipropionate (BDP)] in poly(D,L-lactic acid) (PLA)
      nanoparticles, which were prepared by the nanoprecipitation method. Zeta
      potential and size distribution of the nanoparticles were determined by
      electrophoretic mobility determinations and photon correlation spectroscopy,
      respectively. Interactions between the drugs, the PLA nanoparticles and the fused
      silica capillary were investigated by electrokinetic capillary chromatography
      (EKC). A quantitative CE method was developed for salbutamol sulphate and sodium
      cromoglycate, and the linearity and repeatability of migration times, peak areas
      and peak heights were determined. Microemulsion electrokinetic chromatography was
      used for the quantitative determination of beclomethasone dipropionate. According
      to this study, the applied electromigration techniques were suitable for the
      interaction, drug entrapment and dissolution studies of pharmaceutical
      nanoparticles. The results suggest that even quantitation of the drug located
      inside the nanoparticles was possible. Encapsulation of the more hydrophilic
      model drugs (SS, SCG) in the PLA nanoparticles was less efficient than in the
      case of BDP.

PMID- 18054947
TI  - Supercritical fluid extraction of macrocyclic lactone mycotoxins in maize flour
      samples for rapid amperometric screening and alternative liquid chromatographic
      method for confirmation.
AB  - A rapid and simple method for the direct screening of macrocyclic lactone
      mycotoxins (zearalenone, ZON; alpha-zearalenol, alpha-ZOL; and beta-zearalenol,
      beta-ZOL) in maize flour samples is proposed. The sample screening method
      comprises supercritical fluid extraction (SFE) and clean-up on Florisil
      adsorption cartridge of the selected toxic compounds, followed by continuous flow
      electrochemical detection. Those samples for which the total concentration is
      close to or above the threshold limit established by legislation (0.200 mg kg(
      1)) are subjected to preconcentration on C18 chromatographic material and liquid
      chromatographic separation for confirmation purposes. This confirmation method
      allows the determination of ZON, alpha-ZOL and beta-ZOL in the range between 30
      and 300 microg kg(-1), with a average relative standard deviation lower than 5.2
      in all cases.

PMID- 18054948
TI  - Quasi-flow injection analysis for rapid determination of caffeine in tea using
      the sample pre-treatment method with a cartridge column filled with
      polyvinylpolypyrrolidone.
AB  - The sample pre-treatment method using a polyvinylpolypyrrolidone (PVPP) cartridge
      column combined with a quasi-flow injection analysis (quasi-FIA) system realized
      the rapid determination of caffeine in three types of tea, green, oolong and
      black tea. The measurement time for each tea sample pre-treated using a PVPP
      cartridge column was shortened to 20s. In the present system, the limits of
      detection and quantification were 0.3 microM (1.5 pmol injected) and 0.7 microM
      (3.5 pmol injected), respectively, and a linear calibration curve was afforded up
      to 800 microM (4 nmol injected). Within-run precision of analysis of standard
      solutions of 10 and 100 microM caffeine was 0.11 and 0.16% (n=6), respectively.
      Between-run precision of analysis of the same solutions over 6 days was 0.78 and
      0.74% (n=6), respectively. Comparison with the conventional HPLC method indicated
      that the present quasi-FIA method using sample pre-treatment with a PVPP
      cartridge column was useful for the simple and precise determination of caffeine
      in green, oolong and black tea samples.

PMID- 18054949
TI  - Chiral separation of selected proline derivatives using a polysaccharide-type
      stationary phase by supercritical fluid chromatography and comparison with high
      performance liquid chromatography.
AB  - Chiral separation of selected proline derivatives was conducted on a
      polysaccharide-type chiral stationary phase (CSP) using supercritical fluid
      chromatography (SFC). Effect of both modifier percentage and column temperature
      was studied. As modifier content decreased, the retention and selectivity
      increased. However, retention was decreased as temperature increased from 30
      degrees C to 40 degrees C. In comparison to high-performance liquid
      chromatography (HPLC), better resolution was achieved for Boc-2-methylproline
      using SFC along with a shorter run time. Selectivity is impacted less by change
      of ethanol content in the mobile phase under SFC conditions than with HPLC.
      Chiral recognition mechanism under SFC and HPLC conditions was also examined.
      With SFC, the contribution from hydrogen bonding is most likely a dominant
      interaction for retention rather than chiral recognition. This is supported by
      the limited thermodynamic data and the elution order change for Boc-proline
      between SFC and HPLC. Linearity, injection repeatability and limit of
      quantitation were determined for Boc-2-methylproline.

PMID- 18054950
TI  - Surface free energy of sulfur--revisited II. Samples solidified against different
      solid surfaces.
AB  - The apparent surface free energy of yellow and orange samples of sulfur
      crystallized at the surface of gold, silicon, and Teflon and in air was evaluated
      from the advancing and receding contact angles of water. The samples were
      prepared by casting melted rhombic mineralogical specimen sulfur onto the surface
      of the above-noted solids. Yellow samples were obtained when just melted sulfur
      (ca. 120 degrees C) was cast onto the surfaces, and the orange ones, when the
      melted sulfur was heated longer to a higher temperature (ca. 160 degrees C) and
      then cast onto the surfaces. The obtained results show that the apparent surface
      free energy depends on which surface it crystallized. The greatest value is for
      the sample crystallized at the gold surface, which is 35% higher than that
      crystallized in air. Generally, the surface free energy of orange samples is
      slightly higher than that of yellow ones. It is believed that the differences in
      the energy result from changes in the packing and structural orientation of
      sulfur atoms on the surfaces.

PMID- 18054951
TI  - Methods for functionalization of microsized polystyrene beads with titania
      nanoparticles for cathodic electrophoretic deposition.
AB  - Functionalization of colloidal particles based on the use of polyelectrolytes and
      heterocoagulation was combined with electrophoretic deposition (EPD), with the
      aim of depositing titania-polystyrene (TiO(2)-PS) composite particles on Ti6Al4V
      substrates. The composite particles were obtained by heterocoagulation of TiO(2)
      nanoparticles on the surface of monosized polystyrene beads of 4.6 microm in
      diameter. Two alternative methods were developed for the preparation of the
      TiO(2)-PS suspensions in organic fluids for cathodic electrodeposition. The first
      method was carried out in alkaline aqueous medium with the use of
      polyelectrolytes and intermediate control measurements of zeta potential,
      conductivity, and pH; the second one was carried out directly in the organic
      solvent used for EPD, typically isopropanol. Examples of deposits obtained by EPD
      in both suspensions and a comparative analysis between the two methods are
      presented.

PMID- 18054952
TI  - Adsorption behavior of statherin and a statherin peptide onto hydroxyapatite and
      silica surfaces by in situ ellipsometry.
AB  - The salivary protein statherin is known to adsorb selectively onto hydroxyapatite
      (HA), which constitutes the main mineral of the tooth enamel. This adsorption is
      believed to be crucial for its function as an inhibitor of primary (spontaneous)
      and secondary (crystal growth) precipitation of calcium phosphate salts present
      in saliva. A fragment corresponding to the first 21 N-terminus amino acids of
      statherin (StN21) was previously found to reduce the rate of demineralization of
      HA. Therefore, the interfacial properties of this peptide and statherin onto
      silica, hydrophobized silica and HA discs was studied by in situ ellipsometry.
      Their reversibility induced by dilution and elutability induced by buffer and
      sodium dodecyl sulfate (SDS) was also determined. The results revealed that
      statherin adsorbed at a greater extent onto the HA as compared to StN21,
      suggesting that the hydrogen bonding between the uncharged polar residues at the
      C-terminal region of statherin and HA contributes to its adsorption. However, on
      both silica surfaces the peptide adsorption appeared to proceed in a similar way.
      Onto the hydrophobized silica the adsorption of both peptides was suggested to
      occur either via multilayer formation or adsorption of aggregates from solution,
      while onto the hydrophilic silica adsorption of peptide aggregates from solution
      was the suggested mechanism. Further, both peptides were observed to be strongly
      adsorbed onto HA, even after SDS treatment, in comparison to the layers adsorbed
      onto hydrophobized silica. Both peptide layers were found to be weakly adsorbed
      onto the hydrophilic silica surface as they were totally removed by buffer
      dilution.

PMID- 18054953
TI  - Electrolyte effect on mixed micelle and interfacial properties of binary mixtures
      of cationic and nonionic surfactants.
AB  - In the present work, the adsorption behavior at the liquid-air interface and
      micellization characteristics of mixtures of cetyltrimethylammonium bromide
      (CTAB) and p-(1,1,3,3-tetramethylbutyl) polyoxyethylene (TritonX-100) in aqueous
      media containing different concentrations of NaBr were investigated by surface
      tension and potentiometry measurements. From plots of surface tension (gamma) as
      a function of solution composition and total surfactant concentration, we
      determined the critical micelle concentration (CMC), minimum surface tension at
      the CMC (gamma(CMC)), surface excess (Gamma(max)), and mean molecular surface
      area (A(min)). On the basis of regular solution theory, the compositions of the
      adsorbed film (Z) and micelles (X(M)) were estimated, and then the interaction
      parameters in the micelles (beta(M)) and in the adsorbed film phase (beta(sigma))
      were calculated. For all mole fraction ratios, the results showed synergistically
      enhanced ability to form mixed micelles as well as surface tension reduction.
      Furthermore beta was calculated by considering nonrandom mixing and head group
      size effects. It was observed that, for both the planar air/aqueous interface and
      micellar systems, the nonideality decreased as the amount of electrolyte in the
      aqueous medium was increased. This was attributed to a decrease of the surface
      charge density caused by increasing the concentration of bromide ions.

PMID- 18054954
TI  - Generation and application of new rat monoclonal antibodies against synthetic
      FLAG and OLLAS tags for improved immunodetection.
AB  - Previously, we prepared monoclonal antibodies (mAbs) by immunizing rats with the
      recombinant fusion proteins of mouse Langerin/CD207, which contained a flexible
      linker sequence from E. coli OmpF and a FLAG epitope. We found many of new rat
      mAbs were not reactive to mouse Langerin, and here we identify the epitopes of
      two of these IgG mAbs, L2 and L5, and assess their efficacy in various
      immunodetection methods. MAb L5 is a rat IgG mAb against the FLAG epitope, which
      detected both N-terminal and C-terminal FLAG tagged protein 2 to 8 times better
      than the conventional anti-FLAG mAb M2 by Western blot. For mAb L2, we found its
      epitope to be a 14 amino acid sequence SGFANELGPRLMGK which consisted of both
      sequences from the OmpF derived linker and mouse Langerin. This epitope sequence
      was named OLLAS (E. coliOmpF Linker and mouse Langerin fusion Sequence), and mAb
      L2 as mAb OLLA-2. When the OLLAS sequence was inserted into recombinant proteins
      at N-terminal, C-terminal, or internal sites, the OLLAS tag was detected by mAb
      OLLA-2 with very high sensitivity compared to other conventional epitope tags and
      anti-tag mAbs. MAb OLLA-2 recognized OLLAS tagged proteins with at least 100-fold
      more sensitivity than anti-FLAG M2 and anti-V5 mAbs in Western blot analyses. We
      also find the OLLAS epitope to be superior in immunoprecipitation and other
      immunodetection methods, such as fluorescent immunohistochemistry and flow
      cytometry. In the process, we successfully utilized the OLLAS epitope sequence as
      an internal linker for fusion between the engineered mAb and the antigen, and
      thus achieved improved immunodetection.

PMID- 18054955
TI  - Caveolin-3 expression and caveolae are required for isoflurane-induced cardiac
      protection from hypoxia and ischemia/reperfusion injury.
AB  - Volatile anesthetics protect the heart from ischemia/reperfusion injury but the
      mechanisms for this protection are poorly understood. Caveolae, sarcolemmal
      invaginations, and caveolins, scaffolding proteins in caveolae, localize
      molecules involved in cardiac protection. We tested the hypothesis that caveolae
      and caveolins are essential for volatile anesthetic-induced cardiac protection
      using cardiac myocytes (CMs) from adult rats and in vivo studies in caveolin-3
      knockout mice (Cav-3(-/-)). We incubated CM with methyl-beta-cyclodextrin
      (MbetaCD) or colchicine to disrupt caveolae formation, and then exposed the
      myocytes to the volatile anesthetic isoflurane (30 min, 1.4%), followed by
      simulated ischemia/reperfusion (SI/R). Isoflurane protected CM from SI/R [23.2+/
      1.6% vs. 71.0+/-5.8% cell death (assessed by trypan blue exclusion), P<0.001] but
      this protection was abolished by MbetaCD or colchicine (84.9+/-5.5% and 64.5+/
      6.1% cell death, P<0.001). Membrane fractionation by sucrose density gradient
      centrifugation of CM treated with MbetaCD or colchicine revealed that buoyant
      (caveolae-enriched) fractions had decreased phosphocaveolin-1 and caveolin-3
      compared to control CM. Cardiac protection in vivo was assessed by measurement of
      infarct size relative to the area at risk and cardiac troponin levels. Isoflurane
      induced a reduction in infarct size and cardiac troponin relative to control
      (infarct size: 26.5%+/-2.6% vs. 45.3%+/-5.4%, P<0.01; troponin: 27.7+/-4.4 vs.
      77.7+/-11.8 ng/ml, P<0.05). Isoflurane-induced cardiac protection was abolished
      in Cav-3(-/-) mice (infarct size: 53.4%+/-6.1% vs. 53.2%+/-3.5%, P<0.01;
      troponin: 102.1+/-22.3 vs. 105.9+/-8.2 ng/ml, P<0.01). Isoflurane-induced cardiac
      protection is thus dependent on the presence of caveolae and the expression of
      caveolin-3. We conclude that caveolae and caveolin-3 are critical for volatile
      anesthetic-induced protection of the heart from ischemia/reperfusion injury.

PMID- 18054956
TI  - Structure of the Yersinia enterocolitica type III secretion translocator
      chaperone SycD.
AB  - Many Gram-negative bacteria use a type III secretion (T3S) system to directly
      inject effector molecules into eucaryotic cells in order to establish a symbiotic
      or pathogenic relationship with their host. The translocation of many T3S
      proteins requires specialized chaperones from the bacterial cytosol. SycD belongs
      to a class of T3S chaperones that assists the secretion of pore-forming
      translocators and, specifically chaperones the translocators YopB and YopD from
      enteropathogenic Yersinia enterocolitica. In addition, SycD is involved in the
      regulation of virulence factor biosynthesis and secretion. In this study, we
      present two crystal structures of Y. enterocolitica SycD at 1.95 and 2.6 A
      resolution, the first experimental structures of a T3S class II chaperone
      specific for translocators. The fold of SycD is entirely alpha-helical and
      reveals three tetratricopeptide repeat-like motifs that had been predicted from
      amino acid sequence. In both structures, SycD forms dimers utilizing residues
      from the first tetratricopeptide repeat motif. Using site-directed mutagenesis
      and size exclusion chromatography, we verified that SycD forms head-to-head
      homodimers in solution. Although in both structures, dimerization largely depends
      on the same residues, the two assemblies represent alternative dimers that
      exhibit different monomer orientations and overall shape. In these two distinct
      head-to-head dimers, both the concave and the convex surface of each monomer are
      accessible for interactions with the SycD binding partners YopB and YopD. A SycD
      variant carrying two point mutations in the dimerization interface is properly
      folded but defective in dimerization. Expression of this stable SycD monomer in
      Yersinia does not rescue the phenotype of a sycD null mutant, suggesting a
      physiological relevance of the dimerization interface.

PMID- 18054957
TI  - Projection structure of yidC: a conserved mediator of membrane protein assembly.
AB  - Bacteria, mitochondria and chloroplasts harbour factors that facilitate the
      insertion, folding and assembly of membrane proteins. In Escherichia coli, yidC
      is required for membrane insertion, acting in both a Sec-dependent and a Sec
      independent manner. There is an expanding volume of biochemical work on its role
      in this process, but none so far on its structure. We present the first of this
      class of membrane proteins determined by electron cryomicroscopy in the near
      nativelike state of the membrane. yidC forms dimers in the membrane and each
      monomer has an area of low density that may be part of the path transmembrane
      segments follow during their insertion. Upon consideration of the structures of
      yidC and SecYEG, we speculate on the nature of the interfaces that facilitate the
      alternative pathways (Sec-dependent and -independent) of membrane protein
      insertion.

PMID- 18054958
TI  - Implications of the progressive self-association of wild-type human factor H for
      complement regulation and disease.
AB  - Factor H (FH) is a major regulator of complement alternative pathway activation.
      It is composed of 20 short complement regulator (SCR) domains and is genetically
      associated as a risk factor for age-related macular degeneration. Previous
      studies on FH suggested that it existed in monomeric and dimeric forms. Improved
      X-ray scattering and analytical ultracentrifugation methodology for wild-type FH
      permitted a clarification of these oligomeric properties. Data at lower
      concentrations revealed a dependence of the X-ray radius of gyration values on
      concentration that corresponded to the weak self-association of FH. Global
      sedimentation equilibrium fits indicated that a monomer-dimer equilibrium best
      described the data up to 1.3 mg/ml with a fitted dissociation constant K(D) of 28
      microM and that higher oligomers formed at increased concentrations. The K(D)
      showed that about 85-95% of serum FH will be monomeric in the absence of other
      factors. Size-distribution analyses in sedimentation velocity experiments showed
      that monomeric FH was the major species but that as many as six oligomeric forms
      co-existed with it. The data were explained in terms of two weak dimerisation
      sites recently identified in the SCR-6/8 and SCR-16/20 fragments of FH with
      similar K(D) values. These observations indicate a mechanism for the progressive
      self-association of FH and may be relevant for complement regulation and the
      formation of drusen deposits that are associated with age-related macular
      degeneration.

PMID- 18054959
TI  - Donor-strand exchange in chaperone-assisted pilus assembly revealed in atomic
      detail by molecular dynamics.
AB  - Adhesive multi-subunit fibres are assembled on the surface of many pathogenic
      bacteria via the chaperone-usher pathway. In the periplasm, a chaperone donates a
      beta-strand to a pilus subunit to complement its incomplete immunoglobulin-like
      fold. At the outer membrane, this is replaced with a beta-strand formed from the
      N-terminal extension (Nte) of an incoming pilus subunit by a donor-strand
      exchange (DSE) mechanism. This reaction has previously been shown to proceed via
      a concerted mechanism, in which the Nte interacts with the chaperone:subunit
      complex before the chaperone has been displaced, forming a ternary intermediate.
      Thereafter, the pilus and chaperone beta-strands have been postulated to undergo
      a strand swap by a 'zip-in-zip-out' mechanism, whereby the chaperone strand zips
      out, residue by residue, as the Nte simultaneously zips in, although direct
      experimental evidence for a zippering mechanism is still lacking. Here, molecular
      dynamics simulations have been used to probe the DSE mechanism during formation
      of the Saf pilus from Salmonella enterica at the atomic level, allowing the
      direct investigation of the zip-in-zip-out hypothesis. The simulations provide an
      explanation of how the incoming Nte is able to dock and initiate DSE due to
      inherent dynamic fluctuations within the chaperone:subunit complex. In the
      simulations, the chaperone donor strand was seen to unbind from the pilus
      subunit, residue by residue, in direct support of the zip-in-zip-out hypothesis.
      In addition, an interaction of a residue towards the N-terminus of the Nte with a
      specific binding pocket (P*) on the adjacent pilus subunit was seen to stabilise
      the DSE product against unbinding, which also proceeded in the simulations by a
      zippering mechanism. Together, the study provides an in-depth picture of DSE,
      including the first atomistic insights into the molecular events occurring during
      the zip-in-zip-out mechanism.

PMID- 18054960
TI  - Temperament and character of suicide attempters.
AB  - Temperamental features are strongly associated with suicidal behaviors both in
      general population and clinical samples. In the present study we considered the
      association between personality traits, measured by Temperament and Character
      Inventory (TCI), and suicidal behavior. We analyzed five samples: a German
      control sample of 1148 healthy individuals; 144 German suicide attempters
      affected by Mood (n=101), Schizophrenia spectrum (n=20) and Borderline
      Personality (n=23) Disorders; 46 Italian suicide attempters affected by Mood
      Disorders (UP=15; BP=31); 76 German non-suicide Mood Disorder patients; 147
      Italian non-suicide Mood Disorder patients. Suicide attempters showed higher
      scores in Harm Avoidance (HA) and lower scores in Self-Directedness (SD) and
      Cooperativeness (C), when compared to controls. Nevertheless, comparing the
      German and the Italian suicide attempter groups with the non-suicide Mood
      Disorder patient groups, no differences were detected. This could be due to the
      effect of Mood Disorder on personality. In conclusion, the present study reveals
      the difficulty to disentangle the personality profile of suicide attempters from
      their psychopathology. Those findings may be useful for cautions in further
      dissecting this complex phenotype.

PMID- 18054961
TI  - Effects of estrogen on lifespan and motor functions in female hSOD1 G93A
      transgenic mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive disease which is caused by
      degeneration of motor neurons in the central nervous system. The incidence of ALS
      is higher in men than women, but the female advantage disappears with increased
      age. Here, we report evidence that the female advantage is due to the protective
      role of estrogen. In an ALS mouse model carrying the human Cu/Zn superoxide
      dismutase (hSOD1) G93A transgene, ovariectomy did not alter the onset age of the
      disease while reducing the female lifespan by 7 days and making it comparable to
      that of the male transgenic mice. Treatment of ovariectomized females with 17beta
      estradiol (E2) did not delay the onset of disease, but prevented progression of
      ALS motor dysfunctions as shown by extension reflex test for a limited time
      window. Importantly, E2 treatment rescued the lifespans in overiectomized
      females. These findings will provide important new insights to interpretation of
      disease progression in post-menopausal female ALS patients.

PMID- 18054962
TI  - Retinal nerve fiber layer thickness is associated with brain MRI outcomes in
      multiple sclerosis.
AB  - Multiple sclerosis is characterized by the dual pathological processes of
      inflammation and neurodegeneration. Conventional MRI techniques are considered
      the best tools for assessing and monitoring lesion burden and inflammation but
      are limited in their ability to assess axonal loss. Optical coherence tomography
      (OCT) is a simple high-resolution technique that uses near infrared light to
      quantify the thickness of the retinal nerve fiber layer (RNFL), which contains
      only non-myelinated axons. RNFL thickness (RNFLT) was measured using OCT on
      thirty consecutive MS patients (60 eyes). Eighteen patients underwent
      quantitative MRI analysis including T1- and T2-lesion volumes (LV), normalized
      brain volume (NBV), normalized cortical, white and gray matter volumes (NCV,
      NWMV, and NGMV), and mean whole brain diffusivity (MD). There was a strong
      association between NBV and average RNFL thickness (p<0.001, partial rp=0.77).
      The T2-LV and NWMV were significantly associated with average RNFL thickness
      (p=0.002, partial rp= -0.76 and p=0.005, partial rp=0.68, respectively) and there
      were trends toward association with T1-LV (p=0.041) and NGMV (p=0.067). There was
      negative correlation between average RNFL thickness (average of both eyes) and
      disability as assessed by EDSS (p=0.02). The results support potential usefulness
      of OCT for MS patient monitoring and research applications.

PMID- 18054963
TI  - Characterization of human ASIC2a homomeric channels stably expressed in murine
      Ltk- cells.
AB  - ASIC2a (BNaC1 or MDEG) is distributed throughout the nervous system and
      potentially involved in mechanosensation, hearing, vision, and taste functions.
      However, pharmacological properties of ASIC2 homomers including the mechanism of
      inhibition by amiloride remain unclear. In this study, we describe the properties
      of hASIC2a stably expressed in Ltk(-) cells, the first reported stable cell line
      expressing any ASICs subunit, by standard whole cell voltage clamp method. In
      response to pH 4.0, at -80 mV, hASIC2a cells exhibited rapidly activating fast
      transient inward current ( approximately 100 pA/pF) that was followed by a
      sustained current ( approximately 13 pA/pF). In contrast, untransfected Ltk(-)
      cells showed only a very small rapidly activating non-inactivating inward current
      ( approximately 4 pA/pF). The magnitude of hASIC2a transient current was pH
      dependent with pH(50) values for activation and inactivation of approximately 4.2
      and approximately 5.5, respectively. Ion substitution experiments revealed the
      following rank order of permeability: Na(+)>K(+)>Ca(2+) for the transient
      current. Amiloride reversibly inhibited the pH 4.0 evoked transient current with
      IC(50) values of approximately 20 microM at both -30 and -80 mV holding
      potentials, indicating that the interactions are voltage independent when nearly
      all amiloride is protonated. Amiloride (100 microM) did not inhibit ASIC2a
      transient current when pre-applied in pH 7.4 and pH 4.0 currents obtained in
      absence of amiloride, but it did inhibit currents when co-applied at pH 4.0
      suggesting open channel blockade. In summary, ASIC2a stable cell line serves as a
      useful model system to study the pharmacological properties of ASIC2a currents,
      potentially contributing to pH-evoked responses in cells of the dorsal root
      ganglion and the central nervous system.

PMID- 18054965
TI  - Influence of bioturbation by Hediste diversicolor on mercury fluxes from
      estuarine sediments: a mesocosms laboratory experiment.
AB  - Mercury, with its reactive forms being the most deleterious for the trophic
      chains, has been identified as a major pollutant in a few confined bodies of the
      coastal zone. Due to feeding, burrowing, and bioirrigation activities, infauna
      are known to play a crucial role in the biogeochemical processes of contaminants.
      The main goal of the present study is to evaluate the effects of Hediste
      diversicolor bioturbation on mercury fluxes from estuarine sediments in a
      mesocosms laboratory experiment. Additionally, an attempt was made to establish a
      relationship between the amount of remobilised mercury to the water column and
      the degree of contamination of the sediments using a mercury contamination
      gradient. The present experiment demonstrated that the bioturbation activity
      caused by the gallery-diffuser H. diversicolor did not influence the
      remobilisation of mercury (in dissolved reactive forms) from the sediment to the
      water column. The concentration of dissolved reactive mercury in the water column
      also did not reflect the degree of contamination in the sediments. The results
      obtained were in accordance with the sediment characteristics of the Mondego
      Estuary and Ria de Aveiro (Portugal), since they are very rich in organic matter
      content, iron/manganese total and hydrous oxides. These physicochemical
      characteristics of the sediments may partially justify the retention of mercury
      by these systems, even when they are subjected to bioturbation. In conclusion,
      sediments with high organic matter content and a high concentration of
      iron/manganese hydrous oxides allowed for efficient retention of mercury, and the
      bioturbation process did not seem to affect the system. Another conclusion from
      this study is that the remobilisation of mercury by bioturbation to the water
      column is not a fast process, requiring more than 24h. This study constitutes an
      important work in the area of the effects of bioturbation on mercury
      remobilisation. Considering the toxicity of mercury for the biota, it is
      essential to evaluate the real magnitude of mercury processes occurring in
      estuarine systems in order to obtain essential information on metal behaviour.

PMID- 18054964
TI  - Desensitization of herpesvirus-encoded G protein-coupled receptors.
AB  - Members of the herpesvirus family, including human cytomegalovirus (HCMV) and
      Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8), encode G protein-coupled
      receptor (GPCR) homologs, which strongly activate classical G protein signal
      transduction networks within the cell. In animal models of herpesvirus infection,
      the viral GPCRs appear to play physiologically important roles by enabling viral
      replication within tropic tissues and by promoting reactivation from latency.
      While a number of studies have defined intracellular signaling pathways activated
      by herpesviral GPCRs, it remains unclear if their physiological function is
      subjected to the process of desensitization as observed for cellular GPCRs. G
      protein-coupled receptor kinases (GRK) and arrestin proteins have been recently
      implicated in regulating viral GPCR signaling; however, the role that these
      desensitization proteins play in viral GPCR function in vivo remains unknown.
      Here, we review what is currently known regarding viral GPCR desensitization and
      discuss potential biological ramifications of viral GPCR regulation by the host
      cell desensitization machinery.

PMID- 18054966
TI  - Identification of fuel samples from the Prestige wreckage by pattern recognition
      methods.
AB  - A set of 34 worldwide crude oils, 12 distilled products (kerosene, gas oils, and
      fuel oils) and 45 oil samples taken from several Galician beaches (NW Spain)
      after the wreckage of the Prestige tanker off the Galician coast was studied. Gas
      chromatography with flame ionization detection was combined with chemometric
      multivariate pattern recognition methods (principal components analysis, cluster
      analysis and Kohonen neural networks) to differentiate and characterize the
      Prestige fuel oil. All multivariate studies differentiated between several groups
      of crude oils, fuel oils, distilled products, and samples belonging to the
      Prestige's wreck and samples from other illegal discharges. In addition, a
      reduced set of 13 n-alkanes out of 36, were statistically selected by Procrustes
      Rotation to cope with the main patterns in the datasets. These variables retained
      the most important characteristics of the data set and lead to a fast and cheap
      analytical screening methodology.

PMID- 18054967
TI  - Comparison of benthic foraminiferal and macrofaunal responses to organic
      pollution in the Firth of Clyde (Scotland).
AB  - By comparing benthic foraminiferal and macrofaunal responses to sewage sludge
      disposal in the Firth of Clyde (Scotland), we wanted to investigate the
      possibility of using foraminifera as bio-indicators of marine environmental
      degradation. Both groups present a similar distributional pattern, with poor
      faunas composed of species tolerant to strong oxygen depletion near to the
      disposal site, surrounded by high density of opportunistic species. Farther away,
      faunal density decreases and equilibrium taxa gradually replace opportunistic
      species. No more environmental impact is perceptible beyond 3 km. Nevertheless,
      some differences exist: foraminifera appear to be more impacted at the disposal
      site, probably as a consequence of the low pH, a supplementary stress factor for
      organisms provided with a calcareous test. At 3 km west of the disposal site,
      macrofauna is comparable to the reference station, whereas foraminifera still
      indicate environmental degradation, suggesting their higher sensitivity to this
      type of pollution. It appears that benthic foraminifera may add valuable
      information to open marine environmental monitoring.

PMID- 18054968
TI  - Organochlorine contaminants in bonnethead sharks (Sphyrna tiburo) from Atlantic
      and Gulf estuaries on the US east coast.

PMID- 18054969
TI  - The effects of a midbrain glioma on memory and other functions: a longitudinal
      single case study.
AB  - Our understanding of the effects of midbrain damage on cognition is largely based
      on animal studies, though there have been occasional investigations of the
      effects of human midbrain lesions on cognition. This investigation of a rare case
      of a glioma initially confined to the dorsal midbrain explores the effects of
      disease progression on IQ, memory, and choice reaction time. Extensive dorsal
      midbrain damage did not appear to affect IQ and various memory functions
      (including span, working memory, story recall, and remote memory). Choice
      reaction time latencies increased, while verbal and spatial learning and long
      term memory deteriorated with tumour growth, but it was not clear how far the
      deterioration reflected midbrain damage or damage outside the midbrain.

PMID- 18054970
TI  - Reduced startle reflex and aversive noise perception in patients with
      orbitofrontal cortex lesions.
AB  - In the present study, the primary emotional response represented by the acoustic
      startle reflex was investigated in a group of six male patients, selected with
      lesions of the orbitofrontal cortex, and twenty matched healthy controls.
      Accurate neuropsychological assessment and lesion mapping showed relatively
      spared cognitive functioning in the patient group, most of the lesions being
      confined to the bilateral polar orbitofrontal cortex. Patients had significant
      inhibition of startle amplitude, together with a reduced self-evaluated
      perception of the unpleasantness of the acoustic probe stimulus. Results add to
      current literature on the circuit of the human startle reflex, by suggesting
      cortical-limbic down-regulation of the orbitofrontal cortex on the main startle
      pathway, probably at the level of the activating reticular system. The
      orbitofrontal cortex, together with the amygdala, is confirmed to represent the
      main center organizing both primary and secondary learned aspects of emotions.

PMID- 18054972
TI  - Insulin resistance in an energy-centered perspective.
AB  - Insulin resistance, of which the incidence is dramatically increasing in Western
      societies, is usually regarded as a pathological condition. However, arguments
      can be provided that insulin resistance may be a normal physiological mechanism
      to let cells and organs deal with the competition for various sources of energy,
      especially under circumstances of energy stress. Here we review four different
      hypotheses dealing with insulin resistance: the glucose-fatty acid cycle, the ER
      and oxidative stress response, the selfish brain, and the thrifty/not-so-thrifty
      genotype. Each hypothesis has a specific view on insulin resistance, but they
      also can complement each other. Combining the four hypotheses supports the view
      that physiological insulin resistance is indeed one of the adaptive regulation
      mechanisms, which has benefit for survival of the organism by restoring and
      maintaining the energy balance at the cellular and organism level. In principle
      insulin resistance seems to be a reversible physiological trait implying that
      there may be a specific mechanism to down-regulate insulin resistance once the
      energy balance is regained. The combined model also describes several ways, by
      which insulin resistance is promoted during prolonged increased energy supply. A
      better understanding of the complex background of physiological insulin
      resistance and of the nature of its regulatory mechanisms will be valuable for
      the treatment of pathological insulin resistance and type 2 diabetes. The present
      review may be helpful for this.

PMID- 18054971
TI  - Medial temporal-lobe damage and memory for emotionally arousing odors.
AB  - Recently, we found that healthy young adults remember odors leading to large
      emotional reactions better than odors provoking smaller emotional reactions.
      Because the amygdala is believed to be critically implicated in memory for
      emotionally arousing information and because it is part of the primary olfactory
      area, we hypothesized that patients with a unilateral medial temporal-lobe
      resection including the amygdala would not show enhanced memory for arousing
      compared to nonarousing odors. We tested odor memory in 19 patients (10 left, 9
      right) who had undergone a unilateral medial temporal-lobe resection including
      the amygdala (MTLR) for treatment of intractable epilepsy and 19 healthy control
      subjects. Healthy individuals and patients with left or right MTLR showed
      comparable subjective emotional reactions to odors. Similarly, healthy
      individuals and patients with MTLR remembered unpleasant odors better than
      pleasant ones. However, unlike healthy individuals, patients with MTLR did not
      show better memory for emotionally arousing odors compared to nonarousing ones.
      Patients undergoing a MTLR, whether in the left or right hemisphere, lose the
      specific memory advantage that odors causing strong emotional reactions normally
      have.

PMID- 18054973
TI  - Six naphthylisoquinoline alkaloids and a related benzopyranone from a Congolese
      Ancistrocladus species related to Ancistrocladus congolensis.
AB  - From the roots of a recently discovered Ancistrocladus taxon, with close
      affinities to Ancistrocladus congolensis regarding molecular ITS sequence data,
      six naphthylisoquinoline alkaloids, 5'-O-demethylhamatine (2), 5'-O
      demethylhamatinine (3), 6-O-demethylancistroealaine A (4), 6,5'-O,O
      didemethylancistroealaine A (5), 5-epi-6-O-methylancistrobertsonine A (6), and 5
      epi-4'-O-demethylancistrobertsonine C (7), have been isolated, along with a
      likewise benzopyranone carboxylic acid, 8. The structural elucidation succeeded
      by chemical, spectroscopic, and chiroptical methods. Their bioactivities were
      tested against protozoan parasites causing severe tropical diseases. Furthermore,
      eight known related alkaloids were identified.

PMID- 18054974
TI  - Assessment of 17alpha-ethinylestradiol effects and underlying mechanisms in a
      continuous, multigeneration exposure of the Chinese rare minnow (Gobiocypris
      rarus).
AB  - 17alpha-Ethinylestradiol (EE(2)) is a synthetic estrogen used primarily in birth
      control pills and in hormone replacement therapy. Owing to its occurrence in
      surface waters at concentrations frequently greater than 1 ng/l and its projected
      future use, EE(2) is expected to pose a significant risk to aquatic organisms.
      This study was conducted to obtain long-term exposure data necessary for the
      establishment of water quality criteria and to investigate mechanisms associated
      with toxic effects. In a multigeneration experiment, Chinese rare minnows
      (Gobiocypris rarus) were constantly exposed to environmentally relevant
      concentrations of the synthetic estrogen EE(2). Mortality, deformities,
      reproductive parameters, plasma vitellogenin and histopathology were assessed.
      The results showed that, in the F(0) generation, all endpoints were significantly
      affected at concentrations higher than 0.2 ng/l EE(2). No F(1) phenotypic males
      developed to maturity at 0.2 ng/l and, when adult females of this exposure group
      were crossed with unexposed males, no F(2) fertile eggs were produced. Kidney
      histopathology and ultrastructure suggest anomalies possibly associated with
      increased vitellogenin accumulation. We concluded that the reproduction of the
      F(1) minnows was completely inhibited at the lowest concentration tested, 0.2
      ng/l EE(2), a concentration frequently detected in surface waters. Growth effects
      may be related to increased energy requirements including the energy used in VTG
      synthesis. Reproductive effects are presumably associated with male feminization
      and the occurrence of testis-ova in males; however, ovarian degeneration observed
      in females may also have contributed to reproductive failure.

PMID- 18054975
TI  - Cigarette smoke decreases mitochondrial porin expression and steroidogenesis.
AB  - Steroidogenic acute regulatory protein (StAR) facilitates the movement of
      cholesterol from the outer to inner mitochondrial membrane for steroidogenesis.
      Here, we investigated the effect of cigarette smoke (CS) on steroidogenesis using
      adrenal mitochondria isolated from mice chronically exposed to CS.
      Steroidogenesis was decreased approximately 78% in CS-exposed mitochondria, as
      measured by synthesis of the steroid hormone precursor pregnenolone. This effect
      was accompanied by decreased mitochondrial import of (35)S-StAR. Further
      characterization of the imported (35)S-StAR by native gradient PAGE revealed the
      presence of a high molecular weight complex in both control and CS-exposed
      groups. Following density gradient fractionation of (35)S-StAR that had been
      extracted from control mitochondria, precursor StAR could be found in fractions 2
      6 and smaller-sized StAR complexes in fractions 6-13. In the CS-exposed group,
      the appearance of precursor shifted from fraction 1-6 and the smaller complexes
      in fractions 6-9 disappeared. Mass spectrometric analysis revealed that the (35)S
      StAR-associated protein complex was composed of several resident matrix proteins
      as well as the OMM resident, VDAC. VDAC expression was greatly reduced by CS, and
      blockage of VDAC with Koenig's polyanion decreased pregnenolone synthesis in
      isolated mitochondria. Taken together, these results suggest that VDAC may
      participate in steroidogenesis by promoting StAR interaction with the OMM and
      that CS may inhibit steroidogenesis by reducing VDAC-StAR interactions.

PMID- 18054976
TI  - Characterization of a novel psi-conotoxin from Conus parius Reeve.
AB  - The M-superfamily of conotoxins currently comprises three major groups of
      peptides (the mu-, kappaMu-, and psi-families) that share a key structural
      characteristic, the six-cysteine motif CC-C-C-CC, but differ with respect to
      their molecular targets. The psi-family consists of M-superfamily conotoxins that
      are nicotinic acetylcholine receptor (nAChR) antagonists. To date, only two psi
      conotoxins, PIIIE and PIIIF, are known, both of which were isolated from a single
      Conus species, Conus purpurascens. In this paper, we report the discovery and
      initial characterization of a psi-conotoxin from another Conus species, Conus
      parius, which we designated as PrIIIE. Its amino acid sequence, inferred from a
      cloned cDNA, differed significantly from those of PIIIE and PIIIF. Its
      bioactivity was investigated by using the synthetic form of the peptide in mice
      and fish bioassays. At 2.5 nmol, the synthetic peptide induced flaccid paralysis
      in goldfish in ca. 4 min but did not induce any remarkable behavior in mice
      (after i.c. and i.p. injection of up to 10 nmol of peptide) and did not block
      action potential in directly stimulated frog muscle preparations.
      Electrophysiological experiments carried out to measure inhibition of ion
      currents through mouse nAChR receptors expressed in oocytes revealed that PrIIIE
      (IC(50) approximately 250 nM) was significantly more potent than PIIIE (IC(50)
      approximately 7000 nM) and that PrIIIE showed higher inhibition potency against
      the adult-type than the fetal-type nAChR. In similar electrophysiological assays,
      PrIIIE showed no inhibitory effects against the mouse muscle subtype Na(+)
      channel isoform Na(v) 1.4. The discovery of this psi-conotoxin from a Conus
      species that belongs to the subgenus Phasmoconus, which is distinct from and
      larger than the clade in which C. purpurascens belongs, suggests that greater
      structural and functional diversity of psi-conotoxins remains to be discovered
      from the members of this subgenus.

PMID- 18054977
TI  - Functional studies of host-specific ephrin-B ligands as Henipavirus receptors.
AB  - Hendra virus (HeV) and Nipah virus (NiV) are closely related paramyxoviruses that
      infect and cause disease in a wide range of mammalian hosts. To determine whether
      host receptor molecules play a role in species-specific and/or virus-specific
      infection we have cloned and characterized ephrin-B2 and ephrin-B3 ligands from a
      range of species, including human, horse, pig, cat, dog, bats (Pteropus alecto
      and Pteropus vampyrus) and mouse. HeV and NiV were both able to infect cells
      expressing any of the ephrin-B2 and ephrin-B3 molecules. There did not appear to
      be significant differences in receptor function from different species or
      receptor usage by HeV and NiV. Soluble ephrin ligands, their receptors and G
      specific human monoclonal antibodies differentially blocked henipavirus
      infections suggesting different receptor affinities, overlapping receptor binding
      domains of the henipavirus attachment glycoprotein (G) and that the functional
      domains of the ephrin ligands may be important for henipavirus binding.

PMID- 18054978
TI  - In vivo alteration of humoral responses to HIV-1 envelope glycoprotein gp120 by
      antibodies to the CD4-binding site of gp120.
AB  - The binding of antibodies to the CD4-binding site (CD4bs) of the HIV-1 envelope
      glycoprotein gp120 has been shown to induce gp120 to undergo conformational
      changes that can expose and/or shield specific epitopes on gp120. Here, we study
      alterations in the antigenicity and immunogenicity of gp120 when complexed with
      human monoclonal antibodies (mAbs) specific for the CD4bs of gp120. The data
      showed that gp120 bound by anti-CD4bs mAbs had enhanced reactivity with mAbs to
      the V3 and N-terminal regions, but not with mAb to the C terminus. Moreover, mice
      immunized with the gp120/anti-CD4bs mAb complexes produced higher titers of gp120
      specific serum IgG and IgA than mice immunized with uncomplexed gp120 or other
      gp120/mAb complexes. Notably, the enhanced antibody production was directed
      against V3 and correlated with better exposure of V3 on the gp120/anti-CD4bs mAb
      complexes. The higher antibody reactivity was evident against the homologous
      V3(LAI) peptide, but not against heterologous V3 peptides. Potent neutralization
      activity against HIV-1(LAI) was also observed in the sera from mice immunized
      with gp120/anti-CD4bs mAb complexes, although the sera exhibited poor
      neutralizing activities against other viruses tested. These results indicate that
      the anti-CD4bs antibodies alter the antigenicity and immunogenicity of gp120,
      leading to enhanced production of anti-gp120 antibodies directed particularly
      against the V3 region.

PMID- 18054980
TI  - Change in the accommodative force on the lens of the human eye with age.
AB  - The aim of the study was to determine the age-dependence of the accommodative
      force on the lens in order to make it clear whether the causes of presbyopia are
      due to lenticular or extralenticular changes. A finite element model of the lens
      of an 11-, 29- and 45-year-old human eye was constructed to represent the fully
      accommodated state. Subsequently, the force that was needed to mould the lens
      into its unaccommodated state was calculated. The force on the lens appeared to
      be preserved with age, with only a slight increase to a value of approximately
      0.06N. In conclusion, the preservation of the net force delivered by the
      extralenticular ciliary body indicates that the causes of presbyopia must be
      ascribed to lenticular changes.

PMID- 18054979
TI  - Human macrophages support persistent transcription from unintegrated HIV-1 DNA.
AB  - Retroviruses require integration of their RNA genomes for both stability and
      productive viral replication. In HIV infection of non-dividing, resting CD4 T
      cells, where integration is greatly impeded, the reverse transcribed HIV DNA has
      limited biological activity and a short half-life. In metabolically active and
      proliferating T cells, unintegrated DNA rapidly diminishes with cell division.
      HIV also infects the non-dividing but metabolically active macrophage population.
      In an in vitro examination of HIV infection of macrophages, we find that
      unintegrated viral DNA not only has an unusual stability, but also maintains
      biological activity. The unintegrated linear DNA, 1-LTR, and 2-LTR circles are
      stable for at least 30 days. Additionally, there is persistent viral gene
      transcription, which is selective and skewed towards viral early genes such as
      nef and tat with highly diminished rev and vif. One viral early gene product Nef
      was measurably synthesized. We also find that independent of integration, the HIV
      infection process in macrophages leads to generation of numerous chemokines.

PMID- 18054981
TI  - Aging disrupts the neural transformations that link facial identity across views.
AB  - Healthy human aging can have adverse effects on cortical function and on the
      brain's ability to integrate visual information to form complex representations.
      Facial identification is crucial to successful social discourse, and yet, it
      remains unclear whether the neuronal mechanisms underlying face perception per
      se, and the speed with which they process information, change with age. We
      present face images whose discrimination relies strictly on the shape and
      geometry of a face at various stimulus durations. Interestingly, we demonstrate
      that facial identity matching is maintained with age when faces are shown in the
      same view (e.g., front-front or side-side), regardless of exposure duration, but
      degrades when faces are shown in different views (e.g., front and turned 20
      degrees to the side) and does not improve at longer durations. Our results
      indicate that perceptual processing speed for complex representations and the
      mechanisms underlying same-view facial identity discrimination are maintained
      with age. In contrast, information is degraded in the neural transformations that
      represent facial identity across views. We suggest that the accumulation of
      useful information over time to refine a representation within a population of
      neurons saturates earlier in the aging visual system than it does in the younger
      system and contributes to the age-related deterioration of face discrimination
      across views.

PMID- 18054982
TI  - Visual pigment and oil droplet characteristics of the bobolink (Dolichonyx
      oryzivorus), a new world migratory bird.
AB  - The retinal photoreceptors of a New World migratory bird, the bobolink
      (Dolichonyx oryzivorus) were examined using microspectrophotometry. Based on the
      absorbance spectra of their visual pigments and oil droplets, retinal
      photoreceptors include five classes of single cones, one double cone, and one
      rod. The single cones contain a long-wavelength pigment (lambda(max)=564nm)
      paired with a red or clear droplet, a medium-wavelength pigment
      (lambda(max)=505nm) with an orange or yellow droplet, and an ultraviolet pigment
      (lambda(max)=372nm) with a transparent droplet. No violet- or blue-sensitive
      single cone was found. The Bobolink double cone is unique: the Accessory member
      possesses the violet sensitive pigment (lambda(max)=403nm), in contrast to the
      long-wavelength sensitive pigment present in the double cones of other avian
      species.

PMID- 18054983
TI  - Priming of Pop-out provides reliable measures of target activation and distractor
      inhibition in selective attention.
AB  - Recent research has demonstrated a striking role for intertrial priming in visual
      search. When searching for a discrepant target, repetition of the target feature
      speeds search, an effect known as Priming of Pop-out (PoP). In two experiments
      involving color singletons, we identified two independent components of PoP,
      target activation and distractor inhibition. Each component was reflected by two
      measures, a repetition benefit and a switching cost, that were highly correlated.
      Large individual differences on each component were observed and persisted when
      test and retest were separated by one week. The results suggest that PoP may be a
      reliable tool for assessing individual differences on target activation and
      distractor inhibition in selective attention.

PMID- 18054984
TI  - The function of cation-binding agents in the enzymatic treatment of municipal
      sludge.
AB  - Treatment of sludge with enzymes has previously been shown to efficiently release
      organic matter. However, the added enzymes were partially adsorbed to, entrapped
      by or bound to the sludge structure. Simultaneous decrease of enzymes activities
      was observed. Reduced adsorption and more effective, lower, enzyme dose was
      achieved in sludge pre-treated with three cation-binding agents. The enzymatic
      solubilisation of sludge was improved by 150%, 240% and 290%, by 50mM sodium
      tripolyphosphate (STPP), 25mM citric acid (CA) or 50mM
      ethylenediaminetetraacetate (EDTA), respectively. With cation binders, the lower
      relative enzyme dose 0.2 (13.7mg/g total solids (TS)) released 3.5 times higher
      COD than enzyme dose 1 (68.5mg/g TS) alone. In the presence of 25mM CA, 75% added
      protease remained soluble. In the presence of 50mM CA, EDTA or STPP, 50% of alpha
      amylase and cellulase remained soluble. At 200mM STPP, alpha-amylase was
      inactive, and the efficiency of enzymatic sludge hydrolysis decreased. CA was the
      most effective of the three cation-binding agents tested. It is biodegradable and
      can be produced endogenously by the microorganisms in sludge. CA has the greatest
      potential for the practical application to enhance biogas production. This paper
      reports on the possible mechanisms of enzymes adsorption to the sludge matrix and
      possible methods of decreasing the adsorption. We suggest that steric hindrances
      were responsible for the decreased enzymatic sludge solubilisation and that
      polyvalent metal ions were directly involved in adsorption of enzymes to sludge
      matrix. The addition of cation binders eliminated both phenomena and thereby
      improved the enzymatic solubilisation of sludge.

PMID- 18054985
TI  - Removal of mono-valent oxyanions from water in an ion exchange membrane
      bioreactor: influence of membrane permselectivity.
AB  - The ion exchange membrane bioreactor (IEMB) proved to be an effective technology
      for the removal of nitrate and perchlorate from polluted drinking water when
      using a mono-anion permselective membrane such as Neosepta ACS. Aiming at
      reducing the cost of the system, this study evaluates the use of a lower-cost
      anion exchange membrane, which exhibits no preferential mono-anion permselective
      properties. With this purpose an Excellion I-200 membrane was tested, for the
      removal of anionic micropollutants, such as nitrate and perchlorate from drinking
      water supplies. The impact of the lower anion permselectivity of this membrane on
      the quality of the treated water was determined. It was demonstrated that
      differences between the membrane properties are responsible for the different
      permselectivities observed towards multi-valent and mono-valent anions. The use
      of Excellion I-200 resulted in a less selective removal of perchlorate and
      nitrate, allowing anions such as sulphate and phosphate species to be
      transported. When treating 3.1l/m(2)h of water contaminated with 100microg/l of
      perchlorate and 60mg/l of nitrate, lower removal degrees were obtained (85% of
      perchlorate and 88% of nitrate), compared with 96% of perchlorate and 99% of
      nitrate achieved with the Neosepta ACS membrane, operating under the same
      conditions. However, the Excellion I-200 membrane shows no target anion flux
      decline during a relatively long period of operation (1 month) and no secondary
      contamination of the treated water by the carbon source used. These
      characteristics are essential for a membrane to be successfully used in the IEMB
      system. Additionally, the selection of the membrane depends on the latter
      characteristics and on the water quality requirements.

PMID- 18054987
TI  - Low-temperature dechlorination of hexachlorobenzene on solid supports and the
      pathway hypothesis.
AB  - The dechlorination of HCB was carried out under low-temperature and oxygen
      deficient conditions on different solid supports such as SiO(2), CaO, CaSiO(3),
      cement and treated fly ash (tFA). All the tested supports except SiO(2) showed a
      HCB dechlorination potential. The dechlorination efficiencies (D(1)) of HCB by
      CaO, CaSiO(3), tFA and cement reached 64.62%, 76.15%, 79.97% and 32.21% at 350
      degrees C for 4h, respectively. It was thought electrons in the vacancies
      originated from the unsaturated metallic ions and O(2-) on the crystal surfaces
      made the D(1) different between SiO(2), CaO and CaSiO(3). Comparing the D(1) by
      tFA and cement, the high dechlorination potential of tFA was due to the more free
      electrons from the crystal defects and the transition metals, and the more active
      points for the gas-solid phase reaction, which both had positive effects on
      dechlorination reaction. The effect of Cu addition (0.2-5.0%) on HCB
      dechlorination might result from the Ullmann coupling which was not notable in
      enhancing the dechlorination reaction. From the study, we can draw the conclusion
      that the dechlorination potential mainly depends on the support characteristic
      rather than the transition metal content. Based on this study and previous
      references, the dechlorination/polymerization induced by the electron transfer
      mode was thought to be the dominant pathway while the hydrogen transfer mode was
      minor. The electron was originated from the crystal defects or induced by
      transition metals, and the dissociation of a chloride ion happened forming a
      radical, and then the polymerization of radicals led to the formation of high
      molecular-weight compounds which seemed to cause the material imbalance.

PMID- 18054988
TI  - Determination of zinc speciation in basic oxygen furnace flying dust by chemical
      extractions and X-ray spectroscopy.
AB  - There is a growing concern regarding the environmental and public health risks
      associated with airborne particulate matter (PM). The basic oxygen furnace is one
      of the most important atmospheric dust sources of the steel manufacturing
      process. It emits dust enriched in heavy metal such as Zn, which is assumed to
      contribute to the toxic potential of atmospheric PM. Dust collected before and
      after the filtration system was analyzed to determine Zn speciation. To this end,
      a variety of analytical tools were used and a sequential extraction protocol has
      been specifically developed for iron and steel dust. The Zn speciation results
      obtained by EXAFS and sequential extraction were in excellent agreement. Before
      filtration, the speciation of Zn in BOF was 43% ZnFe(2)O(4), 23% ZnCO(3) and 16%
      ZnO. The same species were detected after filtration with different proportions.
      BOF dust after filtration contains more soluble Zn phases which may play a role
      in the toxic effects of the emissions.

PMID- 18054991
TI  - Telomere length inheritance and aging.
AB  - Telomere shortening accompanies human aging, and premature aging syndromes are
      often associated with short telomeres. These two observations are central to the
      hypothesis that telomere length directly influences longevity. If true,
      genetically determined mechanisms of telomere length homeostasis should
      significantly contribute to variations of longevity in the human population. On
      the other hand, telomere shortening is also observed in the course of many aging
      associated disorders but determining whether it is a cause or a consequence is
      not an easy task. Here, we review the most relevant experimental and descriptive
      data relating telomere length, as a quantitative trait, to aging and longevity.

PMID- 18054990
TI  - Factors impacting human telomere homeostasis and age-related disease.
AB  - Loss of telomere length homeostasis has been linked to age-related disease
      especially cancer. In this review, we discuss two major causes of telomere
      dysfunction that potentially lead to tumorigenesis: replicative aging and
      environmental assaults. Aging has long been recognized as a source for telomere
      dysfunction through increasing numbers of cell divisions in the absence of
      sufficient telomerase activity. However, environmental assaults that cause
      telomere dysfunction are only beginning to be identified and recognized.
      Environmental stressors that influence telomere length may be physical or induced
      by psychological situations like stress. Knowledge of all factors, including
      genetic and environmental forces, that moderate telomere length will be critical
      for understanding basic mechanisms of human telomere maintenance during
      development and aging as well as for disease prevention and treatment strategies.

PMID- 18054989
TI  - Physiological assembly and activity of human telomerase complexes.
AB  - Telomerase is a specialized reverse transcriptase conserved throughout almost all
      eukaryotic life. It plays a fundamental role in genome maintenance, adding back
      the telomeric DNA repeats lost from chromosome ends due to incomplete replication
      or damage. The protein and RNA subunits of telomerase fold and function in a co
      dependent manner to establish a high fidelity of telomeric repeat synthesis. Over
      the past two decades, studies of telomerase have uncovered previously
      unanticipated levels of complexity in its assembly, activity and regulation. This
      review describes the current understanding of telomerase in humans, with
      particular focus on telomerase biogenesis and regulation in its cellular context.

PMID- 18054992
TI  - The total body burden of chromium associated with skin disease and smoking among
      cement workers.
AB  - BACKGROUND: Hand eczema and other skin diseases have been associated with the
      exposure of chromium among cement workers. Studies on skin disease and other
      factors associated with the body burden of chromium are limited. OBJECTIVE: The
      present study investigated the role of skin disease and smoking in the
      association with body burden of chromium among cement workers. METHODS: Forty
      five workers (38 men and 7 women) were recruited for this study and interviewed
      to obtain information on demographic status, lifestyle, employment history, and
      affecting factors. Urine samples were collected to measure the urinary chromium
      concentration to represent the body burden of chromium. RESULTS: The average
      urinary chromium concentration was approximately 6 times higher in non-smoking
      workers with hand eczema than in non-smoking workers with no skin disease (45.5
      vs. 7.6 microg/L). The average chromium level increase to 87.0 microg/L for
      smokers with the disease. Compared with workers with no hand eczema, the odds
      ratio of having urinary chromium concentration exceeding the biological exposure
      index level significantly increased to 11.6 (95% CI=1.3-102.2) for non-smoking
      workers with skin disease, and to 48.0 (95% CI=4.5-510.8) for smoking workers
      with skin disease. The multiple regression analysis showed that the use of gloves
      may reduce significantly the chromium exposure. CONCLUSIONS: Inadequate
      protection and personal behavior increase the internal dose of chromium in cement
      workers. Total body burden of chromium are higher among cement workers with skin
      disease and smoking habit. These workers deserve intervention education on
      personal hygiene to reduce the exposure of chromium.

PMID- 18054993
TI  - Can fluorescence spectrometry be used as a surrogate for the Biochemical Oxygen
      Demand (BOD) test in water quality assessment? An example from South West
      England.
AB  - The fluorescence intensities of tryptophan-like, tyrosine-like and humic-like
      materials were determined using excitation-emission-matrices (EEMs) for a wide
      range of samples including natural surface waters, sewage and industrial
      effluents and waters that have experienced known pollution events from the South
      West of England (n=469). Fluorescence intensities reported in arbitrary
      fluorescence units (AFU) were correlated with standard five day Biochemical
      Oxygen Demand (BOD(5)) values which were used as an indicator of the amount of
      biodegradable organic material present. Tryptophan-like fluorescence, which has
      been found to relate to the activity of the biological community, showed the
      strongest correlation with BOD(5). Fluorescence analysis of the tryptophan-like
      peak (excitation/emission wavelength region 275/340 nm) is found to provide an
      accurate indication of the presence, and relative proportions of bioavailable
      organic material present (natural or anthropogenic). It therefore provides an
      insight relating to its oxygen depleting potential. Thus fluorescence
      spectroscopy is recommended as a portable or laboratory tool for the
      determination of the presence of biodegradable organic matter with intrinsic
      oxidising potential in natural waters. The novel application of Geographically
      Weighted Regression (GWR) to the data illustrates that strong local relationships
      exist between the two parameters and that site specific character may be a strong
      factor in the strength of the tryptophan-like fluorescence/BOD(5) relationship.

PMID- 18054994
TI  - Hepatic levels of metal and metallothioneins in two commercial fish species of
      the Northern Iberian shelf.
AB  - Metal levels (Cd, Pb, Hg, Cr, Fe, Cu, Zn) together with metallothioneins (MTs)
      were determined in the liver of two commercial fish species collected along the
      Northern Iberian coast. The four-spotted megrim (Lepidorhumbos boscii) and the
      pouting (Trisopterus luscus) were selected as representative species of the
      middle/outer (200-500 m) and inner shelf (70-120 m), respectively. Metal
      pollution in the middle/outer shelf was mostly detected in the Asturias and
      Basque Country areas, whereas in the inner shelf, pollution was widely spread
      along the coast. Significantly high levels of Pb, Cd, Cr and Hg were detected in
      T. luscus from different sampling sites and associated to anthropogenic pressure.
      MTs were induced in fish that had higher amounts of Zn, Cd, Cr and Hg in their
      livers, supporting the use of MT as a biomarker of metal exposure. The study
      supports the usefulness of the selected fish species as sentinel organisms for
      future biomonitoring studies.

PMID- 18054995
TI  - Semi-quantitative characterisation of ambient ultrafine aerosols resulting from
      emissions of coal fired power stations.
AB  - Emissions from coal fired power stations are known to be a significant
      anthropogenic source of fine atmospheric particles, both through direct primary
      emissions and secondary formation of sulfate and nitrate from emissions of
      gaseous precursors. However, there is relatively little information available in
      the literature regarding the contribution emissions make to the ambient aerosol,
      particularly in the ultrafine size range. In this study, the contribution of
      emissions to particles smaller than 0.3 mum in the ambient aerosol was examined
      at a sampling site 7 km from two large Australian coal fired power stations
      equipped with fabric filters. A novel approach was employed using conditional
      sampling based on sulfur dioxide (SO(2)) as an indicator species, and a
      relatively new sampler, the TSI Nanometer Aerosol Sampler. Samples were collected
      on transmission electron microscope (TEM) grids and examined using a combination
      of TEM imaging and energy dispersive X-ray (EDX) analysis for qualitative
      chemical analysis. The ultrafine aerosol in low SO(2) conditions was dominated by
      diesel soot from vehicle emissions, while significant quantities of particles,
      which were unstable under the electron beam, were observed in the high SO(2)
      samples. The behaviour of these particles was consistent with literature accounts
      of sulfate and nitrate species, believed to have been derived from precursor
      emissions from the power stations. A significant carbon peak was noted in the
      residues from the evaporated particles, suggesting that some secondary organic
      aerosol formation may also have been catalysed by these acid seed particles. No
      primary particulate material was observed in the minus 0.3 mum fraction. The
      results of this study indicate the contribution of species more commonly
      associated with gas to particle conversion may be more significant than expected,
      even close to source.

PMID- 18054996
TI  - Localization of source regions of selected hydrofluorocarbons combining data
      collected at two European mountain stations.
AB  - Ground-based in situ measurements of hydrofluorocarbons HFC-125, HFC-134a, and
      HFC-152a, which are regulated under the Kyoto Protocol, are carried out at four
      European sites within the SOGE (System of Observation of Halogenated Greenhouse
      Gases in Europe) program. Concentrations measured at the high mountain stations
      of Jungfraujoch (Switzerland) and Mte Cimone (Italy) together with back
      trajectory statistical analysis are used in order to identify potential source
      regions on a European scale. Combining concentration data recorded at the two
      sites allows to reduce one of the problem which is inherent to the back
      trajectory approach, i.e. the localisation of "ghost" sources in the wake of real
      sources. In this way, a more reliable picture of the location of European
      potential source regions is given.

PMID- 18054997
TI  - Potential dermal exposure to deltamethrin and risk assessment for manual
      sprayers: influence of crop type.
AB  - A comparison of the Potential Dermal Exposure (PDE) of workers to the insecticide
      deltamethrin was made as a function of crop type, in small agricultural
      production units in Argentina. Seven experiments were done with two different
      crops (maize and broccoli, treated area between 600 and 1000 m(2)) with three
      different operators under typical field conditions using a lever operated
      knapsack. The methodology is based on the whole body dosimetry technique,
      presenting separately the data for mixing/loading and application activities.
      These results indicate a higher concentration of pesticide in lower body sections
      for broccoli and a wider distribution for maize. The risk inherent in these
      agricultural procedures is estimated through Margin of Safety (MOS) values and
      was found to be generally safe. Preliminary results of a mass balance
      distribution of the pesticide between crop, soil and operator are also presented.

PMID- 18054998
TI  - Co-regulation of redox processes in freshwater wetlands as a function of organic
      matter availability?
AB  - Wetlands have important filter functions in landscapes but are considered to be
      the biggest unknowns regarding their element dynamics under global climate
      change. Information on sink and source function of sulphur, nitrogen, organic
      matter and acidity in wetlands is crucial for freshwater regeneration. Recent
      results indicate that redox processes are not completely controlled by the
      sequential reduction chain (that is electron acceptor availability) but that
      electron donor availability may be an important regulator. Our hypothesis was
      that only sites which are limited in their electron donor availability (low
      concentrations of dissolved organic carbon (DOC)) follow the concept of the
      sequential reduction chain. We compared the results of two freshwater wetland
      systems: 1) three forested fens within a boreal spruce catchment in a low
      mountain range in southern Germany (high DOC regime) and 2) three floodplain
      soils within a groundwater enrichment area in the Rhein valley in northwest
      Switzerland (low DOC regime). Micro scale investigations (a few cm(3)) with
      dialyse chambers as well as soil solution and groundwater concentrations at the
      forested fens (high DOC regime) indicated simultaneous consumption of nitrate and
      sulphate with release of iron, manganese and methane (CH(4)) as well as an
      enrichment in stable sulphur isotopes indicating a co-existence of processes
      attributed to different redox gradients. Soil and aquifer gas measurements down
      to 4.6 m at the groundwater enrichment site (low DOC regime and carbon
      limitation) showed extreme high rates of metabolism with carbon dioxide
      (CO(2))(,) dinitrous oxide (N(2)O) and CH(4) concentrations reaching fifty,
      thirty and three times atmospheric concentrations, respectively. Simultaneously,
      groundwater oxygen (O(2)) saturation was between 50 and 95%. We concluded that
      independent of DOC regime the sequential reduction chain was not a suitable
      concept in our systems. Instead of electron acceptor or donor availability micro
      site variability might explain the co-existence of redox processes within our
      sites.

PMID- 18054999
TI  - Wetland types and wetland maps differ in ability to predict dissolved organic
      carbon concentrations in streams.
AB  - Three categories of digital wetland maps widely available in the United States
      were used to develop models relating wetlands to DOC: (1) wetlands mapped by the
      U.S. National Wetlands Inventory (NWI) (2) wetland vegetation cover mapped by the
      U.S. National Land Cover Dataset (NLCD), and (3) maps of hydric soils. Data
      extracted from these maps for 27 headwater catchments of the Ontonagon River in
      northern Michigan, USA were used with DOC concentrations measured in catchment
      streams to develop stepwise multiple regressions based on wetland area and type.
      The catchments of the 27 tributaries ranged in area from 2 to 66 km(2) and
      wetlands constituted 10 to 53% of their area. Although all three databases
      provided regressions that were highly significant (p<0.001), the variance
      explained was greater for NWI maps (R(2)=0.75) than for NLCD (R(2)=0.61) or soil
      maps (R(2)=0.60). Wetland-stream relationships were strongest during September
      2002, but were significant for nine out of ten dates sampled during subsequent
      seasons. The individual wetland type most highly correlated (r>0.62) with stream
      DOC concentrations was conifer peatland, represented on the NWI maps as
      Palustrine Needle-leaved Forest, the NLCD maps as woody wetland, and the soil
      maps as organic soils. For the NWI dataset, DOC was negatively correlated with
      area of palustrine emergent wetlands (i.e., sedge meadows and graminoid fens) and
      bog shrubs, inferring that these wetland types may be sinks for DOC. Because of
      the different effects of wetland vegetation types on DOC, a GIS data source such
      as the NWI which depicts those wetland types is superior for predicting landscape
      contributions to stream DOC concentrations.

PMID- 18055000
TI  - Long-term clinical and radiological magnetic resonance imaging outcome of abscess
      associated spontaneous pyogenic vertebral osteomyelitis under conservative
      management.
AB  - OBJECTIVES: Management of abscess-associated spontaneous pyogenic vertebral
      osteomyelitis (PVO) is controversial. The role of magnetic resonance imaging
      (MRI) in follow-up and its relation with clinical outcome is often unclear. This
      study evaluates the clinical and MRI outcome of abscess-associated PVO under
      conservative treatment. METHODS: Prospective study and retrospective review of
      patients with spontaneous PVO in whom the initial MRI showed soft-tissue
      involvement (STI). Treatment according to a medical protocol, clinical and MRI
      follow-up at diagnosis, and at 2 later time points: early response (ER, at the
      end of antibiotic therapy) and late response (LR, >or=6 months after therapy).
      MRI classified STI as soft-tissue edema (STE) or abscess. RESULTS: Of the 27
      patients (20 men, 74%, age 65+/-14), all had pain, 17 (63%) had fever, and 6
      (22%) had mild neurological impairment. The main etiology was Staphylococcus sp
      (11, 41%). Twenty-one (81%) had bacteremia and 18 (67%) had epidural/paraspinal
      abscess. Patients received antibiotics for 9 weeks, administered orally for 6
      weeks. ER: Three cases failed and general improvement was seen in the remainder.
      MRI showed persistent STI, which diminished in all cases except 1, whereas
      bone/disc findings remained. LR: All patients were cured; 8 reported mild
      sequelae (30%). MRI still revealed bone/disc abnormalities, but residual STE was
      infrequent. Median follow-up was 29 months. CONCLUSION: Most patients with
      abscess-associated spontaneous PVO are cured with a conservative approach. MRI
      shows STI reduction at ER evaluation. Repeat MRI is probably unnecessary if
      clinical and laboratory outcomes are satisfactory. The persistence of bone/disc
      MRI findings alone does not represent therapeutic failure.

PMID- 18055003
TI  - The future of scientific publishing.

PMID- 18055002
TI  - Anti-coagulant aptamers.
AB  - In the past decade development of aptamer technology is poised into several
      fields with various clinical applications. With this progress, aptamer based anti
      coagulant agents are evolved and continuing their applications with clinical
      trials. At present several anti-coagulant aptamers are available against
      different proteins from blood coagulation cascade. In this review, the mechanism
      and functions of anti-coagulant aptamers, as an alternate candidate to other
      available anti-coagulant agents are discussed.

PMID- 18055005
TI  - Roles for hypoxia-regulated genes during cervical carcinogenesis: somatic
      evolution during the hypoxia-glycolysis-acidosis sequence.
AB  - OBJECTIVES: Malignant phenotypic traits are caused by microenvironmental
      selection pressures during carcinogenesis. Hypoxia can drive a tumor toward a
      more aggressive malignant phenotype. The objective was to better understand the
      role of the hypoxia-regulated genes in cervical carcinogenesis. METHODS: We
      analyzed the expression of the hypoxia-regulated genes, including hypoxia
      inducible factor-1alpha (HIF-1alpha), erythropoietin (Epo), vascular endothelial
      growth factor (VEGF), glucose transporter 1 (GLUT1), carbonic anhydrase IX
      (CAIX), and MET, in cervical cell lines and human tissue samples of cervical
      intraepithelial neoplasia (CIN I-III) and invasive squamous cell carcinoma
      (ISCC). RESULTS: CAIX and MET were expressed in cervical carcinoma cell lines,
      but not in normal or human papillomavirus-immortalized cervical cells. In
      clinical tissue samples, Epo, VEGF, GLUT1, and CAIX were not detected in normal
      squamous epithelia. GLUT1 was expressed in nearly all cases of CIN and ISCC,
      however, CAIX was expressed only in CIN III and ISCC. HIF-1alpha and MET
      expression was confined to the basal cells in normal squamous epithelia and was
      detected in the dysplastic cells of CIN and ISCC. CONCLUSIONS: The role of HIF
      1alpha and MET changes from response to proliferation to tumor progression during
      cervical carcinogenesis. GLUT1 expression, a glycolytic phenotype adaptive to
      glycolysis, occurs early during cervical carcinogenesis and is a specific marker
      for dysplasia or carcinoma. MET and CAIX may contribute tumor progression in
      later stage. CAIX expression, an acid-resistant phenotype, may be a powerful
      adaptive advantage during carcinogenesis. Successful adaptation to the hypoxia
      glycolysis-acidosis sequence in a microenvironment is crucial during
      carcinogenesis.

PMID- 18055006
TI  - Prediction of suboptimal primary cytoreduction in primary ovarian cancer with
      combined positron emission tomography/computed tomography--a prospective study.
AB  - OBJECTIVE: To prospectively identify combined PET/CT predictors of
      incomplete/suboptimal primary cytoreduction in advanced ovarian cancer. METHODS:
      From September 2004 to March 2007, 179 patients with a Risk of Malignancy Index
      (RMI) >150 based on serum CA-125, ultrasound examinations and menopausal state,
      underwent PET/CT within 2 weeks prior to standard surgery/debulking of a pelvic
      tumor. Ten PET/CT features were identified and evaluated as predictors of
      cytoreduction in 54 patients with advanced ovarian cancer. RESULTS: Complete
      cytoreduction (no macroscopic residual disease) was achieved in 35% and optimal
      cytoreduction (<1 cm residual disease) was achieved in 56%. Using univariate
      analysis, predictors of incomplete cytoreduction were large bowel mesentery
      implants (LBMI) (P<0.003), pleural effusion (P<0.009), ascites (P<0.009) and
      peritoneal carcinosis (P<0.01). LBMI (P<0.03) and ascites (P<0.05) were also
      predictors of suboptimal cytoreduction. Using multivariate analysis, LBMI was the
      only independent predictor of incomplete cytoreduction (P=0.004) and no predictor
      of suboptimal cytoreduction was found. CONCLUSION: PET/CT predictors of
      cytoreduction were found. But they should not be used to withhold patients form
      primary cytoreductive surgery. We suggest PET/CT as a supplementary image
      modality prior to surgery in primary OC patients whenever accurate and
      comprehensive preoperative evaluation of primary tumor and metastases is desired.

PMID- 18055007
TI  - Transtheoretical model-based multiple behavior intervention for weight
      management: effectiveness on a population basis.
AB  - BACKGROUND: The increasing prevalence of overweight and obesity underscores the
      need for evidence-based, easily disseminable interventions for weight management
      that can be delivered on a population basis. The Transtheoretical Model (TTM)
      offers a promising theoretical framework for multiple behavior weight management
      interventions. METHODS: Overweight or obese adults (BMI 25-39.9; n=1277) were
      randomized to no-treatment control or home-based, stage-matched multiple behavior
      interventions for up to three behaviors related to weight management at 0, 3, 6,
      and 9 months. All participants were re-assessed at 6, 12, and 24 months. RESULTS:
      Significant treatment effects were found for healthy eating (47.5% versus 34.3%),
      exercise (44.90% versus 38.10%), managing emotional distress (49.7% versus
      30.30%), and untreated fruit and vegetable intake (48.5% versus 39.0%)
      progressing to Action/Maintenance at 24 months. The groups differed on weight
      lost at 24 months. Co-variation of behavior change occurred and was much more
      pronounced in the treatment group, where individuals progressing to
      Action/Maintenance for a single behavior were 2.5-5 times more likely to make
      progress on another behavior. The impact of the multiple behavior intervention
      was more than three times that of single behavior interventions. CONCLUSIONS:
      This study demonstrates the ability of TTM-based tailored feedback to improve
      healthy eating, exercise, managing emotional distress, and weight on a population
      basis. The treatment produced a high level of population impact that future
      multiple behavior interventions can seek to surpass.

PMID- 18055008
TI  - Effects of culture conditions and nuclear transfer protocols on blastocyst
      formation and mRNA expression in pre-implantation porcine embryos.
AB  - This study investigated the effects of culture conditions and somatic cell
      nuclear transfer (SCNT) protocols on in vitro development of porcine SCNT embryos
      and on expression patterns of genes involved in stress (heat shock protein 70.2,
      HSP70.2), trophoblastic function (integrin beta1, ITGB1), metabolism
      (phosphoglycerate kinase 1, PGK1), apoptosis (BAX), and imprinted gene (insulin
      like growth factor 2 receptor, IGF2R). In Experiment 1, supplementing modified
      North Carolina State University (mNCSU) medium with 10% FBS at Day 4 of culture
      increased SCNT blastocyst formation (22.9 vs. 10.7%, P<0.05), number of inner
      cell mass cells (13.3+/-4.3 vs. 7.6+/-2.2, P<0.05), and total cells (57.9+/-19.5
      vs. 36.3+/-8.2, P<0.05) in cloned blastocysts. In Experiment 2, using culture
      medium with 10% FBS, 1.0mM calcium in fusion/activation medium (1.0C), and
      7.5mug/mL cytochalasin B treatment (0.1C&CB) yielded higher rates (P<0.05) of
      blastocysts (33.6 and 33.3%, respectively) relative to the control (0.1mM calcium
      fusion medium, 0.1C; 18.3%). Total cell numbers of blastocysts were increased
      (P<0.05) in 1.0C (77.4+/-28.9) compared to the control (58.5+/-22.6). In vitro
      derived blastocysts had higher expression levels of BAX and lower levels of
      HSP70.2, IGF2R compared to their in vivo-derived counterparts. Supplementing
      culture medium with 10% FBS increased relative abundances of BAX mRNA in SCNT
      blastocysts relative to in vivo-derived blastocysts. The transcript level of
      ITGB1 in blastocyst from 0.1C&CB was lower than in vivo blastocysts. In
      conclusion, different culture conditions or SCNT protocols affected in vitro
      development of SCNT embryos and altered several important genes (BAX, HSP70.2,
      IGTB1, and IGF2R) compared to conventional in vivo-derived blastocysts.

PMID- 18055009
TI  - Osteoconduction and osteoinduction of low-temperature 3D printed bioceramic
      implants.
AB  - Rapid prototyping is a valuable implant production tool that enables the
      investigation of individual geometric parameters, such as shape, porosity, pore
      size and permeability, on the biological performance of synthetic bone graft
      substitutes. In the present study, we have employed low-temperature direct 3D
      printing to produce brushite and monetite implants with different geometries.
      Blocks predominantly consisting of brushite with channels either open or closed
      to the exterior were implanted on the decorticated lumbar transverse processes of
      goats for 12 weeks. In addition, similar blocks with closed channel geometry,
      consisting of either brushite or monetite were implanted intramuscularly. The
      design of the channels allowed investigation of the effect of macropore geometry
      (open and closed pores) and osteoinduction on bone formation orthotopically.
      Intramuscular implantation resulted in bone formation within the channels of both
      monetite and brushite, indicating osteoinductivity of these resorbable materials.
      Inside the blocks mounted on the transverse processes, initial channel shape did
      not seem to significantly influence the final amount of formed bone and
      osteoinduction was suggested to contribute to bone formation.

PMID- 18055010
TI  - Pharmacological characterization of desensitization in scratching behavior
      induced by intrathecal administration of hemokinin-1 in the rat.
AB  - Desensitization is induced by the repeated administration of high doses of
      substance P (SP) or hemokinin-1 (HK-1). However, little information is available
      about the mechanisms involved in the induction of desensitization by these
      peptides. Thus, to characterize this desensitization, we examined the dose
      dependent effect of these peptides, the effect of pretreatment with neurokinin
      1(NK1) receptor antagonists, and the effect of pretreatment with inhibitors of
      protein kinases such as protein kinase A (PKA), protein kinase C (PKC),
      calcium/calmodulin kinase II (CaMKII) and mitogen-activated protein kinase kinase
      (MEK). The number of scratchings induced by 10(-3)M SP or HK-1 decreased
      following pretreatment with 10(-11)-10(-3)M SP or HK-1 with a marked reduction at
      10(-3) and 10(-6)M SP or HK-1. The effect of NK1 receptor antagonists on
      desensitization induced by pretreatment with 10(-6)M SP was marked, whereas there
      was little effect of pretreatment with these antagonists on 10(-6)M HK-1-induced
      desensitization. Additionally, 10(-6)M SP- and HK-1-induced desensitization was
      attenuated by pretreatment with PKA, PKC and MEK inhibitors, except a CaMKII
      inhibitor that inhibited SP-induced desensitization. These results indicate that
      the receptor and kinases involved in HK-1-induced desensitization are partially
      different from those of SP.

PMID- 18055011
TI  - Simultaneous occurrence of the JAK2V617F mutation and BCR-ABL gene rearrangement
      in patients with chronic myeloproliferative disorders.

PMID- 18055012
TI  - Low viral loads and lymphoid organ spheroids are associated with yellow head
      virus (YHV) tolerance in whiteleg shrimp Penaeus vannamei.
AB  - Yellow head virus (YHV) is an invertebrate nidovirus that has caused mass
      mortality in penaeid shrimp since 1990. Several YHV types are known, but only the
      original type (YHV-type 1 or YHV-1) is highly virulent. Most studies have focused
      on acute YHV-1 infections and there is limited work on YHV-1 survivors. We
      compared moribund and surviving (14%) whiteleg shrimp Penaeus (Litopenaeus)
      vannamei from an experimental challenge with YHV-1. Although grossly normal, all
      survivors were positive for YHV-1 by specific, reverse transcriptase polymerase
      chain reaction (RT-PCR) assays, histological analysis or transmission electron
      microscopy (TEM), indicating that they were not resistant but tolerant to YHV-1.
      On the other hand, real-time PCR analysis revealed that mean YHV-1 copies/ng
      total RNA for survivors (2.8x10(4) +/- 6.9x10(4)) were approximately 40 times
      lower (P<0.05) than those in moribund shrimp (1.2x10(6) +/- 6.7x10(5)copies/ng
      total RNA). This was confirmed by strong positive immunohistochemical and in situ
      hybridization (ISH) reactions for YHV-1 in lymphoid organ tubules (LOT) of
      moribund shrimp and weak positive reaction only in lymphoid organ spheroids (LOS)
      of survivors. TEM revealed morphologically complete YHV virions in both groups.
      Furthermore, immuno-TEM and Western blot analysis revealed that YHV-1 structural
      proteins gp116 and p20 were present at comparable reactive levels in each group.
      Thus, YHV-1 tolerance was not associated with absence of gp116 as previously
      reported for palaemonid shrimp. Instead, it was associated with the presence of
      YHV-positive LOS and a relatively low viral load.

PMID- 18055013
TI  - Lead isotopes in environmental sciences: a review.
AB  - Lead (Pb) isotopic analyses proved to be a very efficient tool for tracing the
      sources of local and global Pb pollution. This review presents an overview of
      literature published on the use of Pb isotopic analyses of different
      environmental matrices (atmospheric aerosols, lichens, tree rings, peat deposits,
      lake, stream, marine sediments, soils, etc.). In order to gain more insight, the
      isotopic compositions of major sources of Pb in the environment as determined by
      several authors are described in detail. These include, above all, the former use
      of leaded gasoline, coal combustion, industrial activities (e.g., metallurgy) and
      waste incineration. Furthermore, this review summarises analytical techniques
      (especially ICP-MS) used for the determination of Pb isotopes in environmental
      samples.

PMID- 18055014
TI  - Chemical contaminants in feedlot wastes: concentrations, effects and attenuation.
AB  - Commercial feedlots for beef cattle finishing are potential sources of a range of
      trace chemicals which have human health or environmental significance. To ensure
      adequate protection of human and environmental health from exposure to these
      chemicals, the application of effective manure and effluent management practices
      is warranted. The Australian meat and livestock industry has adopted a proactive
      approach to the identification of best management practices. Accordingly, this
      review was undertaken to identify key chemical species that may require
      consideration in the development of guidelines for feedlot manure and effluent
      management practices in Australia. Important classes of trace chemicals
      identified include steroidal hormones, antibiotics, ectoparasiticides,
      mycotoxins, heavy metals and dioxins. These are described in terms of their
      likely sources, expected concentrations and public health or environmental
      significance based on international data and research. Androgenic hormones such
      as testosterone and trenbolone are significantly active in feedlot wastes, but
      they are poorly understood in terms of fate and environmental implications. The
      careful management of residues of antibiotics including virginiamycin, tylosin
      and oxytetracycline appears prudent in terms of minimising the risk of potential
      public health impacts from resistant strains of bacteria. Good management of
      ectoparasiticides including synthetic pyrethroids, macrocyclic lactones,
      fluazuron, and amitraz is important for the prevention of potential ecological
      implications, particularly towards dung beetles. Very few of these individual
      chemical contaminants have been thoroughly investigated in terms of
      concentrations, effects and attenuation in Australian feedlot wastes.

PMID- 18055015
TI  - The bovine salivary proteins BSP30a and BSP30b are independently expressed BPI
      like proteins with anti-Pseudomonas activity.
AB  - The family of BPI-like proteins are thought to play a role in innate immunity of
      the airways and oral cavity. They have similarities with
      bactericidal/permeability-increasing protein (BPI), an important host defence
      molecule in mammals, in the nucleotide sequence of their mRNAs, organisation of
      exons and their predicted protein structure. We compared the expression and
      function of 2 of the 13 known bovine BPI-like proteins, BSP30a and b, which
      together constitute 30% of the total protein in bovine saliva. Despite their
      recent divergence, we found that the two proteins have unique expression
      patterns, considerable inter- and intra-animal variation in abundance and differ
      in their glycosylation status. Recombinant and native BSP30a and b exhibited
      growth suppression activity against Pseudomonas aeruginosa and Streptococcus
      pneumoniae. Native BSP30a and b had no significant lipopolysaccharide-binding
      activity. These data provide functional evidence supporting a role for the BPI
      like proteins in host defence and suggest that BSP30a and b contribute to the
      growth suppression function of bovine saliva through a mechanism independent of
      LPS opsonisation.

PMID- 18055016
TI  - Synthesis, structure and interactions with DNA of novel tetranuclear,
      [Mn4(II/II/II/IV)] mixed valence complexes.
AB  - Reaction of Mn(II) with phenoxyalkanoic acids and di-2-pyridyl ketone oxime
      (Hpko) leads to neutral tetranuclear complexes of the general formula
      Mn(4)(O)(pko)(4)(phenoxyalkanoato)(4) (phenoxyalkanoic acids: H-mcpa=2-methyl-4
      chloro-phenoxy-acetic acid, H-2,4,5-T=2,4,5-trichloro-phenoxy-acetic acid or H3,4
      D=3,4-dichloro-phenoxy-acetic acid). The compounds were synthesized by adding di
      2-pyridyl ketone oxime to MnCl(2) in the presence of the sodium salts of the
      alkanoic acids in methanol. The crystal structure of
      Mn(4)(II/II/II/IV)(O)(pko)(4)(2,4,5-T)(4).2.5CH(3)OH.0.25H(2)O 1 shows that the
      complex consists of a [Mn(4)(mu(4)-O)](8+) core with a Mn(IV) and 3 Mn(II) ions
      in octahedral environment and a mu(4)-O atom bridging the four manganese ions.
      Spectroscopic studies of the interaction of these tetranuclear clusters with DNA
      showed that these compounds bind to dsDNA. The binding strength of the
      Mn(4)(II/II/II/IV)(O)(pko)(4)(2,4,5-T)(4) complex for calf thymus DNA is equal to
      1.1x10(4)M(-1). Among the deoxyribonucleotides they bind preferentially to
      deoxyguanylic acid (dGMP). Competitive studies with ethidium bromide (EthBr)
      showed that the Mn(4)(II/II/II/IV)(O)(pko)(4)(2,4,5-T)(4) complex exhibited the
      ability to displace the DNA-bound EthBr indicating that the complex binds to DNA
      via intercalation in strong competition with EthBr for the intercalative binding
      site. Additionally, DNA electrophoretic mobility experiments showed that all
      three complexes, at low cluster concentration, are obviously capable of binding
      to pDNA causing its cleavage (relaxation) at physiological pH and temperature. At
      higher cluster concentration, catenated dimer forms of pDNA was formed.

PMID- 18055017
TI  - The dichotomy in the DNA-binding behaviour of ruthenium(II) complexes bearing
      benzoxazole and benzothiazole groups.
AB  - The substituted tris(bipyridine)ruthenium(II) complexes {[Ru(bpy)(2)(4,4'
      bbob)](2+) and [Ru(bpy)(2)(5,5'-bbob)](2+) [where bpy=2,2'-bipyridine and
      bbob=bis(benzoxazol-2-yl)-2,2'-bipyridine] have been prepared and compared to the
      previously studied complex [Ru(bpy)(2)(4,4'-bbtb)](2+) [where
      bbtb=bis(benzothiazol-2-yl)-2,2'-bipyridine]. From the UV/VIS titration studies,
      Delta-[Ru(bpy)(2)(4,4'-bbob)](2+) displays a stronger association than the Lambda
      isomer with calf-thymus DNA (ct-DNA). For [Ru(bpy)(2)(5,5'-bbob)](2+), there
      appears to be minimal interaction with ct-DNA. The results of fluorescence
      titration studies suggest that [Ru(bpy)(2)(4,4'-bbob)](2+) gives an increase in
      emission intensity with increasing ct-DNA concentrations, with an
      enantiopreference for the Delta isomer, confirmed by membrane dialysis studies.
      The fluorescent intercalation displacement studies revealed that [Ru(bpy)(2)(4,4'
      bbob)](2+) and [Ru(bpy)(2)(5,5'-bbob)](2+) display a preference for more open DNA
      structures such as bulge and hairpin sequences. While Lambda-[Ru(bpy)(2)(4,4'
      bbtb)](2+) has shown the most significant affinity for all the oligonucleotides
      sequences screened in previous studies, it is the Delta isomer of the comparable
      benzoxazole ruthenium(II) complex (Delta-[Ru(bpy)(2)(4,4'-bbob)](2+)) that
      preferentially binds to DNA.

PMID- 18055018
TI  - What is reinforced by phasic dopamine signals?
AB  - The basal ganglia have been associated with processes of reinforcement learning.
      A strong line of supporting evidence comes from the recording of dopamine (DA)
      neurones in behaving monkeys. Unpredicted, biologically salient events, including
      rewards cause a stereotypic short-latency (70-100 ms), short-duration (100-200
      ms) burst of DA activity - the phasic response. This response is widely
      considered to represent reward prediction errors used as teaching signals in
      appetitive learning to promote actions that will maximise future reward
      acquisition. For DA signalling to perform this function, sensory processing
      afferent to DA neurones should discriminate unpredicted reward-related events.
      However, the comparative response latencies of DA neurones and orienting gaze
      shifts indicate that phasic DA responses are triggered by pre-attentive sensory
      processing. Consequently, in circumstances where biologically salient events are
      both spatially and temporally unpredictable, it is unlikely their identity will
      be known at the time of DA signalling. The limited quality of afferent sensory
      processing and the precise timing of phasic DA signals, suggests that they may
      play a less direct role in 'Law of Effect' appetitive learning. Rather, the 'time
      stamp' nature of the phasic response, in conjunction with the other signals
      likely to be present in the basal ganglia at the time of phasic DA input,
      suggests it may reinforce the discovery of unpredicted sensory events for which
      the organism is responsible. Furthermore, DA-promoted repetition of preceding
      actions/movements should enable the system to converge on those aspects of
      context and behavioural output that lead to the discovery of novel actions.

PMID- 18055019
TI  - Detecting perinatal common mental disorders in Ethiopia: validation of the self
      reporting questionnaire and Edinburgh Postnatal Depression Scale.
AB  - BACKGROUND: The cultural validity of instruments to detect perinatal common
      mental disorders (CMD) in rural, community settings has been little-investigated
      in developing countries. METHODS: Semantic, content, technical, criterion and
      construct validity of the Edinburgh Postnatal Depression Scale (EPDS) and Self
      Reporting Questionnaire (SRQ) were evaluated in perinatal women in rural
      Ethiopia. Gold-standard measure of CMD was psychiatric assessment using the
      Comprehensive Psychopathological Rating Scale (CPRS). Community-based,
      convenience sampling was used. An initial validation study (n=101) evaluated both
      EPDS and SRQ. Subsequent validation was of SRQ alone (n=119). RESULTS: EPDS
      exhibited poor validity; area under the receiver operating characteristic (AUROC)
      curve of 0.62 (95%CI 0.49 to 0.76). SRQ-20 showed better validity as a
      dimensional scale, with AUROC of 0.82 (95%CI 0.68 to 0.96) and 0.70 (95%CI 0.57
      to 0.83) in the two studies. The utility of SRQ in detecting 'cases' of CMD was
      not established, with differing estimates of optimal cut-off score: three and
      above in Study 1 (sensitivity 85.7%, specificity 75.6%); seven and above in Study
      2 (sensitivity 68.4%, specificity 62%). High convergent validity of SRQ as a
      dimensional measure was demonstrated in a community survey of 1065 pregnant
      women. LIMITATIONS: Estimation of optimal cut-off scores and validity
      coefficients for detecting CMD was limited by sample size. CONCLUSIONS: EPDS
      demonstrated limited clinical utility as a screen for perinatal CMD in this
      rural, low-income setting. The SRQ-20 was superior to EPDS across all domains for
      evaluating cultural equivalence and showed validity as a dimensional measure of
      perinatal CMD.

PMID- 18055020
TI  - Diminished perception of light as a symptom of depression: further studies.
AB  - BACKGROUND: In a previous preliminary report, the perception of a decrease in
      ambient light intensity appeared to be correlated with depression. We
      prospectively studied this potential link in a controlled study. METHODS: The
      question, "I've noticed that the lights in my surroundings seem dimmer than
      usual", was added to the Center for Epidemiologic Studies Depression Scale (CES
      D) questionnaire and administered prospectively to 213 subjects 50-80 years of
      age participating in the Age-Related Eye Disease Study (AREDS). All had visual
      acuity of 20/32 or better in at least one eye. Main outcome measures were the
      relationship between the dimness question answer and severity of depression, and
      the likelihood that patients reporting dimness were depressed. RESULTS: Subjects
      endorsing their surroundings as being dimmer than usual at least some of the time
      had a mean CES-D score of 10.6 (SD=7.0) compared to a mean of 5.5 (SD=5.4) for
      subjects who never noted dimness (t=-4.22, p=.0001). Depressed individuals (CES-D
      > or = 16) were significantly more likely to report dimness than non-depressed
      (CES-D<16) subjects (chi(2)=15.6, p<0.0001). The total CES-D score and the degree
      of reported dimness (0-3) were significantly associated (r=0.31, p<.0001). Using
      a stepwise regression analysis, subjects who reported any dimness were more
      likely to be depressed. LIMITATIONS: A relatively small number of subjects, 38
      (18%), reported dimness requiring us to dichotomize their dimness level in some
      analyses. CONCLUSIONS: Perceived dimness of one's ambient surroundings and
      clinical depression are linked. Health care professionals should inquire about
      this symptom in potentially depressed patients.

PMID- 18055021
TI  - Fetal tolerance in human pregnancy--a crucial balance between acceptance and
      limitation of trophoblast invasion.
AB  - During human pregnancy the semi-allogeneic/allogeneic fetal graft is normally
      accepted by the mother's immune system. Initially the contact between maternal
      and fetal cells is restricted to the decidua but during the 2nd trimester it is
      extended to the entire body. Two contrary requirements influence the extent of
      invasion of extravillous fetal trophoblast cells (EVT) in the maternal decidua:
      anchorage of the placenta to ensure fetal nutrition and protection of the uterine
      wall against over-invasion. To establish the crucial balance between tolerance of
      the EVT and its limitation, recognition of the semi-allogeneic/allogeneic fetal
      cell by maternal leukocytes is prerequisite. A key mechanism to limit EVT
      invasion is induction of EVT apoptosis. Apoptotic bodies are phagocytosed by
      antigen-presenting cells (APC). Peptides from apoptotic cells are presented by
      APC cells and induce an antigen-specific tolerance against the foreign antigens
      on EVT cells. These pathways, including up-regulation of the expression of IDO,
      IFNgamma and CTLA-4 as well as the induction of T(regulatory) cells, are general
      immunological mechanisms which have developed to maintain peripheral tolerance to
      self-antigens. Together these data suggest that the mother extends her
      "definition of self" for 9 months on the foreign antigens of the fetus.

PMID- 18055022
TI  - Inhibitor of apoptosis protein (IAP) profiling in experimental autoimmune
      encephalomyelitis (EAE) implicates increased XIAP in T lymphocytes.
AB  - In multiple sclerosis (MS) and its widely accepted animal model, experimental
      autoimmune encephalomyelitis (EAE), the failure of autoreactive immune cells to
      undergo apoptosis is thought to contribute to CNS tissue damage and disease
      progression. Promoting apoptosis of myelin-reactive immune cells in diseases such
      as MS, may delay disease progression and decrease the frequency and severity of
      relapses. X-linked inhibitor of apoptosis (XIAP) is a potent anti-apoptotic
      protein that inhibits intrinsic, extrinsic, and c-Jun amino-terminal kinase
      mediated apoptosis and was the only member of the inhibitor of apoptosis (IAP)
      family upregulated in whole blood from EAE mice. Similar increases in XIAP were
      also observed in both peripheral and encephalitogenic T lymphocytes. Increased
      XIAP expression in T cells within areas of demyelination in the CNS suggests that
      XIAP may be enhancing cell survival and thereby contributing to disease
      pathology.

PMID- 18055023
TI  - Presence of otitis media with effusion and its risk factors affect serum cytokine
      profile in children.
AB  - Otitis media with effusion (OME) is a condition that has significant impact on
      the quality of life of children. Although the etiology is multi-factorial,
      certain risk factors such as an allergic predisposition, daycare, and cigarette
      smoke exposure contribute to its pathogenesis. OBJECTIVE: (1) To determine
      whether there is a tendency for children with chronic or recurrent OME (cases) to
      have higher serum levels of the T-helper 2 cell (Th-2) allergenic-type cytokines,
      interleukin-4 (IL-4), and IL-5, or the T-helper 1(Th-1) infectious-type
      cytokines, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF
      alpha), compared to children without a history of recurrent OME (controls) and
      (2) to determine any possible correlations between the cytokine levels and risk
      factors associated with OME. METHODS: We analyzed serum levels of these four
      cytokines by enzyme-linked immunosorbent assays of 19 cases and 17 controls.
      RESULTS: Cases, independent of age, had increased levels of serum IL-5 compared
      to controls (p=0.014). While a significant difference in serum IL-4 levels did
      not exist between cases and controls, children exposed to cigarette smoke had
      significantly higher levels of serum IL-4 (p=0.003). While serum levels of IFN
      gamma were statistically significantly higher in cases than controls with
      univariate analysis (p=0.011), when controlling for age and smoke exposure with
      multivariate analyses, the difference did not reach significance (p=0.086).
      CONCLUSION: These results suggest that patients with chronic or recurrent OME and
      those exposed to cigarette smoke mount a Th-2 allergic-like response, as
      demonstrated by their serum cytokines.

PMID- 18055024
TI  - Connecting chemosensitivity, gene expression and disease.
AB  - Omics-based investigations offer potentially powerful readouts that might be
      useful for probing the underlying biology of normal and diseased states,
      identifying novel therapeutic targets and proposing relevant markers for
      designing treatment strategies. A vital component of these investigations
      involves a systematic analysis of gene expression and chemosensitivity data in
      the context of disease states and small molecule probes into the function of
      targets responsible for a disease phenotype. Systematic analysis of chemical and
      pharmacogenetics data offers a possible means to identify novel, small-molecule,
      potentially therapeutic, agents that affect the phenotype of a particular target.
      Elegantly simple in concept, the covariation of genetic and chemosensitivity
      readouts provide a hypothetical link for relating compounds through genomic
      expression profiles to underlying biology.

PMID- 18055025
TI  - The emerging role of TRPV1 in diabetes and obesity.
AB  - The capsaicin receptor transient receptor potential vanilloid subfamily member 1
      (TRPV1) is highly expressed on sensory nerve fibers innervating the pancreas.
      Indeed, the role of TRPV1 in mediating pain during pancreatitis is well
      established. The initial excitation of these nerves by capsaicin is followed by a
      reversible refractory state (desensitization) or, under certain conditions such
      as neonatal treatment, neurotoxicity. Interestingly, ablation of TRPV1-positive
      fibers by subcutaneous capsaicin treatment not only ameliorates pancreatitis pain
      but also diminishes aging-associated weight gain and improves glucose tolerance
      both in mice on a high-fat diet and in rat models of type 2 diabetes. New
      evidence implies an unexpected, pivotal role for TRPV1 in type 1 (autoimmune)
      diabetes. Non-obese diabetic (NOD) mice carry a hypofunctional TRPV1 mutant.
      Ablation of nerves carrying this mutant TRPV1 by capsaicin prevents immune
      mediated destruction of islet beta cells despite the persistence of diabetogenic
      T cells. Collectively, these findings establish a crucial link among sensory
      nerves, obesity and diabetes and identify pharmacological TRPV1 blockade as a
      novel therapeutic approach for diabetes prevention and weight control.

PMID- 18055026
TI  - Inhibition of human coronavirus 229E infection in human epithelial lung cells
      (L132) by chloroquine: involvement of p38 MAPK and ERK.
AB  - The antiviral effects of chloroquine (CQ) on human coronavirus 229E (HCoV-229E)
      infection of human fetal lung cell line, L132 are reported. CQ significantly
      decreased the viral replication at concentrations lower than in clinical usage.
      We demonstrated that CQ affects the activation of p38 mitogen-activated protein
      kinase (MAPK) and extracellular signal-regulated kinase (ERK). Furthermore, p38
      MAPK inhibitor, SB203580, inhibits CPE induced by HCoV-229E infection and viral
      replication. Our findings suggest that CQ affects the activation of MAPKs,
      involved in the replication of HCoV-229E.

PMID- 18055027
TI  - In vivo administration of corticotropin-releasing hormone at remote intervals
      following ischemia enhances CA1 neuronal survival and recovery of spatial memory
      impairments: a role for opioid receptors.
AB  - The contribution of corticotropin-releasing hormone (CRH) in the modulation of
      ischemia-induced cell death in vivo remains unclear. We characterized the impact
      of pre-ischemic administration of CRH (0, 0.1, 1, 5 microg, i.c.v., 15 min prior
      to vessel occlusion) on neuronal damage following global ischemia in rats. The
      injection of 5 microg CRH led to a 37% increase in CA1 neuronal survival compared
      to vehicle-treated ischemic animals, while pre-treatment with alpha-helical CRH
      (9-41) abolished this neuronal protection. A second objective aimed to determine
      whether CRH protection is maintained over weeks when the peptide is administered
      at remote time intervals following ischemia. Compared to vehicle-treated ischemic
      animals, administration of CRH 8h following global ischemia led to a 61% increase
      in CA1 neuronal survival observed 30 days post-ischemia. Neuronal protection
      translated into significant improvement of ischemia-induced spatial memory
      deficits in the radial maze. Finally, our findings demonstrated that selective
      blockade of kappa- and delta-opioid receptors (using nor-binaltorphimine and
      naltrindole, respectively) prior to CRH administration significantly reduced CA1
      neuronal protection. These findings represent the first demonstration of enhanced
      neuronal survival following in vivo CRH administration in a global model of
      ischemia in rats. They also support the idea that CRH-induced neuroprotection
      involves opioid receptors activation.

PMID- 18055028
TI  - Factors affecting the hippocampal BOLD response during spatial memory.
AB  - The hippocampus has long been implicated in spatial memory, from work in rodents
      to imaging and brain lesion studies in humans. However, recent evidence has
      pointed to the recruitment of areas outside the hippocampus proper on spatial
      memory tasks, including the parahippocampal gyrus and precuneus, possibly
      suggesting a more focused role for the hippocampus proper. In this study, a
      virtual version of the standard rodent spatial memory assessment, the Morris
      water task, has been employed during fMRI to investigate the differential
      involvement of these distinct brain areas. Twenty-eight healthy participants
      completed a block designed version of the virtual Morris water task (vMWT) which
      consisted of three conditions: (1) a hippocampal dependent condition during which
      the participants were forced to use distal room cues in the virtual environment
      to navigate to a hidden platform; (2) a non-hippocampal dependent condition
      during which participants were to navigate to a visible platform; (3) a fixation
      period. Activations of the BOLD signal were evident in the hidden condition as
      compared to the visible condition in the parahippocampal gyrus, precuneus, and
      fusiform when analyzed using to a blocked analysis. Moreover, this blocked
      analysis revealed increases in the right hippocampal BOLD signal during fixation.
      However, when hidden trials were compared to visible trials using a post hoc
      event-related analysis focused on the beginning of each trial, activations of the
      right hippocampus are evident. These results support the theory that extra
      hippocampal structures contribute to spatial memory behavior and identify a
      temporally specific involvement of the hippocampus. Furthermore, they
      substantiate previous results reporting hippocampal BOLD increases during
      fixation.

PMID- 18055029
TI  - Are benzodiazepines really anxiolytic? Evidence from a 3D maze spatial navigation
      task.
AB  - The effects of diazepam and chlordiazepoxide were assessed in a 3D maze which is
      a modification of an 8-arm radial maze. Each arm of the maze is attached to a
      bridge radiating from a central platform. Animals exposed for the first time to
      the maze do not venture beyond the line that separate a bridge from an arm. The
      prime criteria set for an anxiolytic effect is whether mice would increase the
      frequency of entries onto arms and increase arm/bridge entries ratio. C57 mice
      readily cross the line on first exposure and make more than 8 arm visits onto
      arms on second exposure, while other strains (CD-1 and Balb/c) hold back and
      rarely cross the line on first exposure and require more sessions to make more
      than 8 arm entries. An anxiolytic drug is expected to encourage intermediate (CD
      1) and high (Balb/c) anxiety mice to adventure onto the arms of the maze and make
      more visits to the arms to comparable levels seen with low anxiety c57 mice. In
      the present report, administration of different doses of diazepam (0.625, 1.25,
      2.5 and 5 mg kg(-1) i.p.) and chlordiazepoxide (5, 10 and 15 mg kg(-1) i.p.) did
      not reduce anxiety in animals, with the lowest dose of diazepam increasing motor
      activity in Balb/c and increasing anxiety in c57 mice while the highest doses of
      both diazepam (2.5 and 5 mg kg(-1) i.p.) and chlordiazepoxide (15 mg kg(-1) i.p.)
      induced mild sedation. Our results raise some concerns about the methodological
      foundations in the current assessment of anxiety and anxiolytic compounds both in
      animal and human studies.

PMID- 18055030
TI  - Development of a marine fish model for studying in vivo molecular responses in
      ecotoxicology.
AB  - A protocol for fixation and processing of whole adult marine medaka (Oryzias
      melastigma) was developed in parallel with in situ hybridization (ISH) and
      immunohistochemistry (IHC) for molecular analysis of in vivo gene and protein
      responses in fish. Over 200 serial sagittal sections (5microm) can be produced
      from a single adult medaka to facilitate simultaneous localization and
      quantification of gene-specific mRNAs and proteins in different tissues and
      subcellular compartments of a single fish. Stereological analysis (as measured by
      volume density, V(v)) was used to quantify ISH and IHC signals on tissue
      sections. Using the telomerase reverse transcriptase (omTERT) gene, omTERT and
      proliferating cell nuclear antigen (PCNA) proteins as examples, we demonstrated
      that it is possible to localize, quantify and correlate their tissue expression
      profiles in a whole fish system. Using chronic hypoxia (1.8+/-0.2 mgO(2)L(-1) for
      3 months) as an environmental stressor, we were able to identify significant
      alterations in levels of omTERT mRNA, omTERT protein, PCNA (cell proliferation
      marker) and TUNEL (apoptosis) in livers of hypoxic O. melastigma (p<0.05).
      Overall, the results suggest that O. melastigma can serve as a model marine fish
      for assessing multiple in vivo molecular responses to stresses in the marine
      environment.

PMID- 18055031
TI  - A case of very late stent thrombosis after bare metal coronary stent
      implantation: a neglected complication.

PMID- 18055032
TI  - Predictors of outcome in patients undergoing PCI. Results of the RIVIERA study.
AB  - BACKGROUND: Limited information is available about clinical outcomes following
      routine percutaneous coronary intervention (PCI) in the current era. This study
      aimed to identify predictors of adverse clinical or angiographic complications
      following PCI in patients from many different countries. METHODS: RIVIERA is a
      multinational, prospective, observational study in patients undergoing elective
      or primary PCI. Consecutive patients (n=7962) were enrolled in 144 hospitals from
      23 countries in four different continents. Primary outcome was death or
      myocardial infarction (MI). The mean age of the patients was 59 years and 77%
      were men; 92% of patients underwent elective and 8% primary PCI. RESULTS: The
      rate of in-hospital outcomes was low: death 0.3%, MI 1%, any bleeding 3.4%.
      Angiographic complications occurred in 8.7% of patients, mainly coronary
      dissection (3.7%) and no reflow (2%). After multivariable analysis, the strongest
      independent predictors of death or MI were clinical presentation with non-ST
      segment elevation acute coronary syndrome or ST-segment elevation myocardial
      infarction and administration of a glycoprotein (GP) IIb/IIIa inhibitor. Radial
      access, thienopyridine pretreatment and anticoagulation with enoxaparin were
      associated with a lower risk of death or MI. Female gender, PCI of coronary
      artery bypass graft, administration of a GP IIb/IIIa inhibitor and combined use
      of enoxaparin and unfractionated heparin were significantly associated with more
      bleeding. Radial access was the only variable associated with less bleeding.
      CONCLUSIONS: Routine PCI appears to be a relatively safe revascularization
      procedure. Many of the variables identified as predictors of adverse cardiac
      outcomes confirm results obtained in recent randomized PCI trials and are
      modifiable, suggesting that further improvements can be made.

PMID- 18055033
TI  - Post coital hemoptysis.
AB  - Ischemic mitral regurgitation is a complication of coronary artery disease
      specifically in the settings of prior myocardial infarction. It is a dynamic
      lesion and its severity may increase with different forms of exercise leading to
      flash pulmonary edema. We present the case of an 81-year-old man with ischemic
      mitral regurgitation who presented with long standing history of hemoptysis
      limited to sexual intercourse only. After a thorough negative work-up for the
      usual causes of hemoptysis, comprehensive right and left cardiac catheterization
      studies revealed marked increase in baseline mitral regurgitation and pulmonary
      capillary wedge pressure with isometric exercise. This case illustrates that
      sexual intercourse, a form of isometric exercise, can cause severe increase in
      ischemic mitral regurgitation and more so compared to other forms of exercise due
      to heightened sympathetic activity, leading to flash pulmonary edema and
      hemoptysis.

PMID- 18055034
TI  - Identification and differentiation of magnetically labeled mesenchymal stem cells
      in vivo in swines with myocardial infarction.
AB  - We aim to track mesenchymal stem cells (MSCs) after magnetically labeling and
      test the ability of these cells differentiate into cardiomyocytes in vivo.
      Therefore, 20 swines were divided into four groups, sham-operated group (n=3);
      acute myocardial infarction (AMI) transplanted with PBS (n=3); labeled MSCs (n=7)
      and unlabeled MSCs (n=7) group. 10(7) labeled or unlabeled cells were
      intracoronary delivered after MI (4.8+/-1.3 days), and serial cardiac MR (3.0T)
      imaging studies were performed at 0, 4 and 8 weeks after transplantation, then
      the results were confirmed by histological and western blot analysis. We
      demonstrated that labeled MSCs can be reliably detected and tracked in vivo using
      MR imaging. In particular, we provided the evidence of regeneration of labeled
      MSCs in vivo by histological examination and western blot analysis.

PMID- 18055035
TI  - Should dental treatment be considered for lowering inflammatory markers in
      hypertensive patients?
AB  - BACKGROUND: While dental treatment has been reported to lower inflammatory marker
      levels, such studies were small and did not involve subjects with cardiovascular
      diseases. The present prospective study examined the effect of interventional
      dental treatment on serum C-reactive protein (CRP) and fibrinogen levels in
      patients with essential hypertension. METHODS: The study enrolled 50 subjects
      (age: 53.1+/-7; 23 men and 27 women) diagnosed with moderate or severe essential
      hypertension. Patient clinical characteristics were as follows: 80% had
      hypercholesterolemia, 72% were obese/overweight, 6% had diabetes mellitus, 16%
      were current smokers, 40% had target organ damage, and the overall general dental
      health status was poor. CRP and fibrinogen levels were assessed prior to
      treatment and again after 6 months. Dental treatment was mainly for periodontal
      disease and dental caries and its complications, and consisted of extractions of
      hopeless teeth, supragingival scaling, subgingival curettage, anti-inflammatory
      rinses and metronidazole treatment. There was a mean 4 treatment sessions per
      patient over 11 weeks. RESULTS: Dental treatment resulted in improved sulcus
      bleeding index (51+/-19 vs. 42+/-17, p<0.001) and approximal plaque index (50+/
      23 vs. 42+/-13, p<0.001) scores, but had no effect on CRP (1.66 vs. 1.2 mg/l,
      p=0.44) or fibrinogen (3.27 vs. 3.22 g/l, p=0.08) levels. CONCLUSIONS: We suggest
      that the lack of effect of dental treatment on CRP and fibrinogen levels could
      have resulted from smaller impact of dental disease on the total inflammatory
      burden in the presence of hypertension and other cardiovascular risk factors.

PMID- 18055036
TI  - Fractional flow reserve--the influence of the collateral circulation.
AB  - Fractional flow reserve (FFR) is a widely used invasive index of coronary artery
      stenosis. FFR is not influenced by haemodynamic parameters (such as blood
      pressure and pulse rate) or by the vessel studied. However, true FFR value may be
      influenced by the presence of major collateral vessels. In this article we
      describe a case demonstrating this observation and discuss a potential
      physiological mechanism to account for this finding.

PMID- 18055037
TI  - Facilitated PCI by combination fibrinolysis or upstream tirofiban in acute ST
      segment elevation myocardial infarction: results of the Alteplase and Tirofiban
      in Acute Myocardial Infarction (ATAMI) trial.
AB  - Direct percutaneous coronary intervention is the generally accepted superior
      strategy in acute ST-segment myocardial infarction. The concept of facilitating
      PCI in order to overcome delay by door-to-balloon time or transport is
      nevertheless of interest. Combination fibrinolysis guarantees higher rates of
      open infarct-related vessels and reduced reocclusion but without reduction of
      mortality. After a pilot trial of facilitated PCI by combination fibrinolysis in
      39 patients with excellent efficacy and high safety we prospectively randomised
      151 patients (96 males, mean age 67.4+/-8.7 years) to combination fibrinolysis
      with 50 mg alteplase and tirofiban and 162 patients (103 males, mean age 65.6+/
      9.4 years) to upstream tirofiban before invasive approach including PCI. TIMI 2
      or 3 flow of infarct-related vessel before intervention as the primary endpoint
      and 30-day mortality, bleeding complication and angiographic proven stent
      thrombosis as secondary endpoints were assessed. 160 matched patients with acute
      PCI and provisional abciximab served as a control group. RESULTS: TIMI 2 or 3
      flow in the infarct-related vessel could be demonstrated in 87% in the
      combination fibrinolysis group, in 42% in the upstream tirofiban group (p<0.0001)
      and 29% in the control group. 30-day mortality was 0.7% versus 5.5% (p<0.02) and
      6.3% in the control group. No differences could be assessed in severe or moderate
      (1.3% vs 1.2% vs 1.2%) and mild bleeding complications (2% vs 1.9% vs 2.5%).
      Stent thrombosis occurred in none of the patients with combination fibrinolysis,
      in 2 patients (1.5%) in the upstream tirofiban group and in 7 cases (4.4%) in the
      control group. CONCLUSIONS: Combination fibrinolysis before PCI leads to
      significantly higher TIMI flow rates of the infarct-related vessel without
      increase in 30-day mortality or in bleeding complications. This strategy needs to
      be further investigated in larger trials and could optimise acute myocardial
      infarction management even without 24-h service of catheter laboratories.

PMID- 18055040
TI  - Altered autonomic neural control of the cardiovascular system in patients with
      polycystic ovary syndrome.
AB  - PURPOSE: Polycystic ovary syndrome (PCOS) is frequently accompanied by the
      presence of cardiovascular risk factors. It has also been recognized that there
      is a significant relationship between the autonomic nervous system and adverse
      cardiac events. Heart rate recovery (HRR) after exercise is a marker of
      parasympathetic activity and attenuation of this parameter has been shown to be
      associated with increased cardiac mortality. A delayed recovery of systolic blood
      pressure (SBP) after peak exercise has been found to have diagnostic value and
      might reflect sympathetic hyperactivity. The analysis of variations in heart rate
      has also been used to determine the balance between sympathetic and vagal nerve
      activities in the heart. Our objective was to determine HRR, the SBP response to
      exercise and heart rate variability (HRV) in patients with PCOS. METHODS: The
      study population consisted of 26 untreated patients with PCOS and 24 healthy
      controls who were matched with respect to age, body mass index and physical
      activity. All subjects underwent symptom-limited exercise tolerance test
      according to a modified Bruce protocol. Following peak exercise, subjects walked
      a 2-min cool-down period. Heart rate recovery was calculated as the difference
      between heart rate at peak exercise and heart rate at the relevant minute of
      recovery. Blood pressure recovery indexes were determined by dividing the
      systolic blood pressure at 1, 2 and 3 min in recovery to the systolic blood
      pressure at peak exercise. RESULTS: HRR at 1 min (HRR1) of the patients with PCOS
      were significantly lower than that of controls (20+/-4 vs 28+/-8 bpm, p<0.0001).
      Although, resting SBP of the two groups were similar (117+/-7 vs 117+/-10 mmHg,
      p=0.663), the SBP of the patients with PCOS at peak exercise were significantly
      higher when compared to controls (172+/-12 vs 156+/-14 mmHg, p<0.0001). In
      addition, the SBP of the patients with PCOS remained significantly elevated when
      compared to controls at the first, second and third minute of recovery (168+/-13
      vs 148+/-15 mmHg, 162+/-13 vs 136+/-16 mmHg, 152+/-17 vs 127+/-15 mmHg,
      respectively, p<0.0001 for all three). The SBP recovery index at 2 and 3 min of
      the patients with PCOS were significantly higher than that of controls (0.93+/
      0.04 vs 0.87+/-0.07, p<0.0001 and 0.87+/-0.07 vs 0.82+/-0.09, p=0.017,
      respectively). Both time domain and frequency domain parameters of patients with
      PCOS were significantly lower than that of controls. CONCLUSION: This study shows
      that the patients with PCOS have attenuated HRR1, exaggerated SBP response to
      exercise which is delayed to recover and a depressed HRV. These findings might
      also suggest alterations in autonomic neurol control of the cardiovascular system
      in this disorder.

PMID- 18055041
TI  - Diagnostic and prognostic value of N-terminal pro B-type natriuretic peptide (NT
      proBNP) in patients with chronic aortic regurgitation.
AB  - BACKGROUND: BNP and its N-terminal fragment NT-proBNP have proven to be of
      diagnostic and prognostic value in patients with valvular aortic stenosis. Data
      regarding those biomarkers in patients with chronic aortic regurgitation (AR) are
      sparse. Thus it was the aim of the present study to evaluate the diagnostic and
      the long term prognostic value of NT-proBNP in patients presenting with AR.
      METHODS AND RESULTS: This study included 60 patients with isolated AR of varying
      severity (AR I mild, AR II moderate and AR III severe) and preserved left
      ventricular function. Patients were followed over a median period of 824 (770
      921) days. NT-proBNP at baseline was related to disease severity and to
      functional status (161 (70-456) pg/ml in AR I, 226 (100-666) pg/ml in AR II and
      1268 (522-5446) pg/ml in AR III (p=0.003)). Patients (n=6) experiencing an
      adverse event had higher NT-proBNP values at baseline as event free survivors
      (1271 (613-2992) pg/ml vs. 215 (92-534) pg/ml; p=0.034). The AUC of the ROC curve
      for NT-proBNP as a predictor for an adverse event was 0.76 (p<0.036) with an
      optimised cut-off value of 602 pg/ml. Consequently, in Kaplan-Meier analysis NT
      proBNP values dichotomised at this cut-off were able to discriminate patients
      with an adverse outcome in the entire study group (Log rank 9.98, p=0.0016) and
      even better in the conservative group (Log rank 26.92, p<0.001). CONCLUSION: NT
      proBNP is linked to disease severity in patients with chronic aortic
      regurgitation reflecting hemodynamic stress due to volume overload. It provides
      prognostic information for the clinical outcome and thus might be a useful
      biomarker for risk stratification.

PMID- 18055042
TI  - Another battlefield for drug-eluting coronary stents: chronic kidney disease.

PMID- 18055043
TI  - Progressive coronary artery aneurysm presenting as acute myocardial infarction.
AB  - Coronary artery aneurysms (CAA) are commonly of atherosclerotic origin and
      asymptomatic. The natural history is uncertain given its uncommon occurrence and
      lack of longitudinal data. We report a case of CAA, presenting with myocardial
      infarction. Follow-up coronary angiography revealed enlargement of the CAA,
      suggesting a progressive nature.

PMID- 18055044
TI  - Significance of CK-elevation in noncompaction with regard to cardiac and
      neuromuscular disease.
AB  - OBJECTIVES: This retrospective study aimed to find out how often CK is elevated
      in left-ventricular hypertrabeculation/noncompaction (LVHT), how often CK
      elevation is due to neuromuscular disorders (NMDs), other cardiac disease, or
      causes other than cardiac or NMD, and how often CK-elevation is associated with
      troponin-T-positivity. METHODS: Electronic records from all LVHT-patients
      diagnosed between 1995-2005 were reviewed for CK, CK-MB, and troponin-T-values,
      frequency of CK-elevation, and causes of CK-elevation. RESULTS: Among 100 LVHT
      patients, electronic records with laboratory data and final reports were
      available in 88. The highest CK-values ranged between 9-5547U/l. In 40 patients
      at least one CK-value was elevated (46%). Only 8 patients were troponin-T
      positive. There was no significant difference of the clinical cardiologic, ECG,
      and echocardiographic parameters between patients with normal and elevated CK.
      Seventy of the 88 patients were seen by a neurologist. A NMD was diagnosed in 57
      patients (81%). CK-elevation was attributed to NMD in 31 patients (79%), to
      causes other than cardiac or NMD in 6 patients (15%), and to cardiac causes in 4
      patients (10%). CONCLUSIONS: CK-elevation occurs in half of the LVHT-patients. CK
      elevation in LVHT is most frequently attributable to NMDs but hardly to cardiac
      disease. CK-elevation in LVHT suggests NMD and prompts neurological
      investigations.

PMID- 18055045
TI  - Bayesian estimation of flock-level sensitivity of detection of Salmonella spp.,
      Enteritidis and Typhimurium according to the sampling procedure in French laying
      hen houses.
AB  - A study was carried out to estimate the prevalence of flocks infected by
      Salmonella spp., S. Enteritidis and S. Typhimurium in 521 French laying-hen farms
      from October 1st 2004 to September 30th 2005 as part of a European Union-wide
      baseline study to define targets for Salmonella reduction in member states. The
      sampling scheme prescribed and financed by the European Commission to detect
      Salmonella in laying-hen flocks was based on 2 dust-samples and 5 faeces-samples
      per farm. A latent-class Bayesian approach for correlated tests was used to
      estimate the sensitivity of detection of reduced sampling schemes corresponding
      to the 16 combinations of 2 dust- and 5 faeces-samples. For each model the full
      sampling scheme (7 samples) and the reduced protocol were considered as two
      correlated tests, the biological principle being identical and the reduced
      protocol being a subset of the full sampling scheme. As the observed apparent
      prevalence in cage flocks was higher than in other systems (barns, outdoor, or
      organic) these two sub-populations were considered separately. Bayesian
      estimation of posterior medians with 95% probability intervals for true
      prevalence in cage flocks were 0.34 (0.29; 0.39) and 0.13 (0.10; 0.18) for
      Salmonella spp. and Salmonella Enteritidis+Typhimurium respectively. In
      alternative flocks posterior medians with 95% probability intervals for true
      prevalence were 0.09 (0.06; 0.13) and 0.05 (0.03; 0.08) for Salmonella spp. and
      Salmonella Enteritidis+Typhimurium, respectively. In cage flocks Bayesian
      estimation of posterior distributions for sensitivity indicated that at least 5
      samples, including 2 dust samples were necessary to attain comparable sensitivity
      levels to the full sampling scheme. In alternative flocks and for Salmonella spp.
      6 samples were required to ensure a comparable sensitivity level to the full
      sampling scheme. Detection sensitivity was improved by increasing the number of
      dust samples in cage farms and by increasing the total number of samples whatever
      their type in alternative farms.

PMID- 18055046
TI  - Free-roaming dogs and cats in central Italy: public perceptions of the problem.
AB  - A cross-sectional telephone survey of randomly selected households examined the
      extent and types of problems associated with free-roaming dogs and cats in the
      Teramo province of Italy. The households were sampled randomly within each
      municipality; municipalities were combined into coastal, central hills and
      mountain regions for analysis. The survey was conducted in May and June of 2004
      with a response rate of 74% (397/536). Ninety percent of respondents (N=356)
      believed that free-roaming dogs and cats were a problem. They were most commonly
      concerned about personal safety, followed by animal welfare, public health and
      environmental sanitation. Sixty-nine percent of respondents (274) actually saw
      free-roaming dogs or cats where they live. While dogs were most commonly seen,
      cats were seen in greater numbers. Overall, 10% (39/297) and 5% (21/397) of
      respondents cared for free-roaming cats and dogs, respectively. Two-thirds of the
      respondents (251/397) believed that animals were abandoned because the owners
      lost interest. About 2/3 of respondents (251/397) reported that the community
      government should have the responsibility for dealing with free-roaming dogs and
      cats. The respondents supported the idea of building more shelters and
      controlling the birth rate as control measures rather than euthanizing dogs and
      cats. The results suggest that free-roaming dogs and cats are a very common sight
      in this part of Italy with substantial concerns by the residents. However,
      concerns about the animals' welfare were clearly raised, supporting the laws that
      make it illegal to euthanize a healthy dog or cat in Italy. Using the information
      from this study, research on the underlying causes of abandonment of dogs and
      cats or failing to sterilize them should be undertaken to begin to address this
      problem. Further, national and regional funding must be provided to support
      existing laws which should help protect and eventually decrease the numbers of
      free-roaming and homeless dogs and cats.

PMID- 18055047
TI  - Rapid lab-on-a-chip profiling of human gut bacteria.
AB  - The human gut microbiota has a substantial impact on human health. Different
      factors such as disease, diet and drug use can have significant impacts on the
      gut microbiota. Therefore, it is of interest to have simple, rapid methods for
      analysis of the composition of the gut microbiota for clinical diagnostic
      purposes. Since only a minor fraction of the gastrointestinal bacterial community
      is presently possible to cultivate, molecular approaches are currently the best
      suited to investigate its composition. However, most of these molecular
      approaches require technical expertise and expensive equipment to run and they
      are not routinely available. Ideally, the analyses should be point-of-care
      options that can be run on a chip. In this study, an existing lab-on-chip (LOC)
      system for sizing/quantifying DNA was combined with length heterogeneity PCR (LH
      PCR), a PCR-based profiling method targeting bacterial 16S rRNA gene sequences,
      to develop a fast, straightforward, reproducible, and economical method for
      profiling bacterial communities. The LOC LH-PCR method was first evaluated using
      a standardized gut cocktail containing genomic DNA from eight different bacterial
      species representing different genera of relevance for human health. The method
      was also tested on DNA that was directly extracted from human faecal samples and
      it was consistently capable of detecting alterations in the bacterial samples
      before and after antibiotic treatment. Although the resolution of the method
      needs improvement, this study represents the first step towards development of a
      diagnostic LOC for profiling gut bacterial communities.

PMID- 18055048
TI  - Identification of molecules preferentially expressed beneath the marginal zone in
      the developing cerebral cortex.
AB  - During cerebral cortical development, the majority of excitatory neurons are born
      near the ventricle and migrate radially toward the marginal zone (MZ). Since the
      cells invariably stop migrating beneath the MZ, neurons are aligned in an "inside
      out" manner in the cortical plate (CP); that is, the early-born and late-born
      neurons are ultimately positioned in the deep and superficial layers,
      respectively. Since dramatic morphological changes occur in cells beneath the MZ,
      several events critical for proper neuronal maturation and layer formation must
      take place. In this study, we screened for molecules strongly expressed beneath
      the MZ, and identified 28 genes that are preferentially expressed in the upper
      half of the mouse CP on both embryonic day (E) 16.5 and E18.5. Expression
      analyses in reeler and yotari mice, in which neurons terminate migration
      throughout the CP, suggested that these genes were indeed related to the events
      beneath the MZ rather than unrelatedly induced by the structures near the brain
      surface. Pathway analyses suggested calcium signaling to have an important role
      in cells beneath the MZ. The gene list presented here will be useful for
      clarifying the molecular mechanisms that control cortical development.

PMID- 18055050
TI  - Effects of sub-lethal concentrations of hexanal and 2-(E)-hexenal on membrane
      fatty acid composition and volatile compounds of Listeria monocytogenes,
      Staphylococcus aureus, Salmonella enteritidis and Escherichia coli.
AB  - In recent years, the interest in the possible use of natural alternatives to food
      additives to prevent bacterial and fungal growth has notably increased. Plants
      and plant products can represent a source of natural alternatives to improve the
      shelf-life and the safety of food. Some of these compounds, i.e. hexanal,
      hexanol, 2-(E)-hexenal and 3-(Z)-hexenol, produced throughout the lipoxygenase
      pathway have important roles in plant defence with a protective action towards
      microbial proliferation in wounded areas. Otherwise, hexanal and 2-(E)-hexenal
      have evidenced a marked antimicrobial activity against food spoilage and
      pathogenic microbial species both in model and real systems. The precise
      mechanisms of action of all these antimicrobial compounds are not yet clear.
      Because the usage of these compounds as antimicrobials in foods has to be
      supported by the comprehension of mechanisms of action of these compounds, the
      overall purpose of this work was to study the modifications of the cell membrane
      and volatile compounds of Listeria monocytogenes, Staphylococcus aureus,
      Salmonella enteritidis and Escherichia coli during the growth in the presence of
      sub-lethal doses of these two aldehydes. The results obtained evidenced that the
      tested molecules induced noticeable modifications of the composition of cell
      membrane and the volatile compounds produced during the growth. Although specific
      differences in relation to the species considered were identified, 2-(E)-hexenal
      and hexanal induced a marked increase of some membrane associated fatty acids,
      both linear and branched fatty acids as well as unsaturated fatty acids, and
      released free fatty acids.

PMID- 18055049
TI  - Effect of oral administration of heat-killed Lactobacillus brevis SBC8803 on
      total and ovalbumin-specific immunoglobulin E production through the improvement
      of Th1/Th2 balance.
AB  - We examined the effect of 59 strains of heat-killed Lactobacillus brevis on
      interleukin (IL)-12 and interferon (IFN)-gamma production from mouse Peyer's
      patch (PP) cells. L. brevis has a great variety of strains that induce the
      production of these cytokines. Some L. brevis strains, which were selected for
      their ability to induce a strong Th1 immune response, inhibited both total
      immunoglobulin E (IgE) and antigen specific IgE production, and improved the
      Th1/Th2 balance by enhancing IL-12 and IFN-gamma and inhibiting IL-4 production
      from ovalbumin (OVA)-sensitized mouse splenocytes. Based on the results of this
      screening, we selected L. brevis SBC8803 as a potent inhibitor of IgE production,
      and investigated the effect of oral administration of heat-killed SBC8803 on IgE
      production in OVA-sensitized mice. OVA-sensitized mice were fed SBC8803 0%
      (control), 0.05%, or 0.5% added diet for 4 weeks during the period of the
      experiment. Total and OVA-specific IgE in the serum of mice, which were fed the
      0.5% added diet, was significantly lower than that of the control diet fed mice.
      The IFN-gamma/IL-4 value, which represents the Th1/Th2 balance, from the 0.5%
      added diet fed mice splenocytes was also significantly higher than that of the
      control diet fed mouse splenocytes. Histamine release from OVA-sensitized mice
      into sera that were induced by the intraperitoneal antigen challenge decreased
      following the oral administration of SBC8803. The inhibition of IgE production
      and histamine secretion by the oral administration of heat-killed SBC8803 was
      probably due to the improvement of the Th1/Th2 balance toward Th1 dominance.

PMID- 18055051
TI  - Behaviour of Saccharomyces cerevisiae wine strains during adaptation to
      unfavourable conditions of fermentation on synthetic medium: cell lipid
      composition, membrane integrity, viability and fermentative activity.
AB  - During must fermentation wine strains are exposed to a variety of biotic and
      abiotic stresses which, when prevailing over the cellular defence systems, can
      affect cell viability with negative consequences on the progression of the
      fermentative process. To investigate the ability of wine strains to survive and
      adapt to unfavourable conditions of fermentation, the lipid composition, membrane
      integrity, cell viability and fermentative activity of three strains of
      Saccharomyces cerevisiae were analysed during hypoxic growth in a sugar-rich
      medium lacking lipid nutrients. These are stressful conditions, not unusual
      during must fermentation, which, by affecting lipid biosynthesis may exert a
      negative effect on yeast viability. The results obtained showed that the three
      strains were able to modulate cell lipid composition during fermentation.
      However, only two of them, which showed highest viability and membrane integrity
      at the end of the fermentation process, reached a fatty acid composition which
      seemed to be optimal for a successful adaptation. In particular, C16/TFA and
      UFA/TFA ratios, more than total lipid and ergosterol contents, seem to be
      involved in yeast adaptation.

PMID- 18055052
TI  - Evaluation of standard and new chromogenic selective plating media for isolation
      and identification of Bacillus cereus.
AB  - In this study, the performance of two new chromogenic plating media (CBC and BCM)
      was compared with two standard selective plating media (PEMBA and MYP)
      recommended by food authorities for isolation, identification and enumeration of
      Bacillus cereus. The four media types were challenged with a strain set
      comprising 100 B. cereus isolates from different origins and with different
      toxigenic potentials (40 food isolates, 40 isolates from food borne outbreaks and
      20 clinical isolates). Additionally, the performance of the plating media for
      analysis of complex samples was assessed using naturally contaminated foods. Our
      survey showed that the new chromogenic media represent a good alternative to the
      conventional standard media. Especially, if laboratory staff are not highly
      trained in identification of B. cereus, the conventional media could lead to
      substantial misidentification and underestimation of food borne illness caused by
      B. cereus. However, there are some B. cereus strains that could not even be
      detected with this new type of chromogenic media. After the fatal
      misidentification of a highly toxic strain, other methods for a conclusive
      identification of B. cereus are needed. Sequence analysis of the plcR gene, a
      pleiotropic regulator of various virulence factors and B. cereus specific
      enzymes, revealed a significant correlation between atypical colony appearance
      and specific variances within the plcR gene sequences of those strains. The
      current concept of selective plating media, utilising PlcR regulated enzyme
      activities for differentiation purposes, should therefore be reconsidered and
      research should be geared towards culture independent methods.

PMID- 18055053
TI  - Selection and screening for enzymes of nitrile metabolism.
AB  - This work critically reviews the assays of nitrile-converting and nitrile-forming
      enzymes (nitrilases, nitrile hydratases, amidases, aldoxime dehydratases). Most
      of the strains producing such enzymes were obtained by selection on media with
      nitriles, amides or aldoximes as nitrogen sources. Activity and
      enantioselectivity of the enzymes was usually assayed by time-consuming
      chromatographic analysis of substrates and the corresponding reaction products.
      Attempts at introducing faster assays resulted in several spectrophotometric
      methods for reaction product (ammonia, hydroxamate, methacrylamide, benzamide,
      etc.) determination. Recently, new methods for colorimetric and fluorimetric
      determination of ammonia have been developed, which appear promising for high
      throughput assays. Alternatively, methods consisting in determination of NADH
      consumed in a coupled amination reaction or pH-responsive methods are promising
      for this purpose. All the above selection and screening methods establish
      fundamental conditions for the design of hierarchical screening projects.
      However, the potential of these principles, in particular spectrophotometric and
      fluorimetric methods, will be probably further exploited and adapted to multiwell
      plate and robotic systems.

PMID- 18055054
TI  - A yeast strain biosensor to detect cell wall-perturbing agents.
AB  - The cell wall is an essential, unique and highly conserved structure in fungi,
      thus representing an ideal set of targets for antifungal drugs. In the model
      yeast S. cerevisiae, the Pkc1-mediated cell integrity signalling pathway is
      essential for maintenance of the cell wall. Adaptation to cell wall stress
      involves the transcriptional activation of genes functionally relevant for cell
      wall remodelling. One of these activated genes, namely MLP1/YKL161c, is an ideal
      indicator of cell wall perturbations, Mlp1p, being almost undetectable under
      normal growth conditions, accumulated in large amounts when cell wall integrity
      was compromised. We have developed a reporter system based on the expression of
      the nourseothricin resistance gene under the control of the regulatory sequences
      of MLP1. Yeast cells transformed with this reporter construct, subjected to a
      cell wall stress, by chemical agents present in the culture medium, attained a
      high level of nourseothricin-resistance with respect to non-stressed cells, as a
      consequence of increased MLP1 expression. A genetically modified S. cerevisiae
      strain (AT-1) including the reporter system integrated into the native MLP1
      chromosomal locus was also developed. This strain was tested against several
      compounds, grouping different mechanisms of yeast growth inhibition, responding
      specifically to cell wall-perturbing agents. Our results demonstrate the
      usefulness and feasibility of the AT-1 strain as a biosensor to perform high
      throughput antifungal screenings for the identification of antifungal compounds
      active on the cell wall.

PMID- 18055055
TI  - Cloning of complete genes for novel hydrolytic enzymes from Antarctic sea water
      bacteria by use of an improved genome walking technique.
AB  - The increased demand for enzymes with new properties makes indispensable the
      development of easy and rapid strategies to obtain complete genes of new enzymes.
      Here a strategy is described which includes screening by PCR of new subtilases
      mediated by Consensus-Degenerate Hybrid Oligonucleotide Primers (CODEHOP) and an
      improved genome walking method to obtain the complete sequence of the identified
      genes. Existing methods of genome walking have many limitations, which make them
      inefficient and time consuming. We have developed an improved genome walking
      method with novel advances to get a simple, rapid and more efficient procedure
      based on cassette-ligation. Improvements consist basically in the possibility of
      a genomic DNA digestion with any restriction enzyme, blunting and 3' adenylation
      of digested DNA by Taq DNA polymerase to avoid self-circularization, followed by
      TA ligation of the adenine 3' overhanging end to the same unphosphorylated oligo
      cassette. The efficiency of the genome walking method was demonstrated by finding
      the unknown ends of all gene fragments tested, previously obtained by CODEHOP
      mediated PCR, including three subtilases (P4, P6 and P7), one xylanase and one
      lipase, from different strains of Antarctic marine bacteria.

PMID- 18055056
TI  - Brain targeting using novel lipid nanovectors.
AB  - The present study shows the potential of novel nanovectors for the delivery of
      lipophilic radionuclides and therapeutic molecules to the brain. Lipid
      nanocapsules (LNC) inhibiting the P-gp pump efflux, were conjugated to OX26
      monoclonal antibodies (OX26 MAb) and Fab' fragments. The OX26 MAb is directed
      against the transferrin receptor (TfR) highly expressed on the cerebral
      endothelium. The specific association of immunonanocapsules to rat brain
      capillary endothelial cells was demonstrated. Biodistribution of
      immunonanocapsules, labeled with a (188)Re lipophilic complex, was determined in
      healthy rats. At 24 h post-injection, the brain concentrations of Fab'
      immunonanocapsules and OX26-immunonanocapsules were, respectively, 1.5 and 2-fold
      higher than non-targeted nanocapsules. In addition, Fab' fragments helped prolong
      the vascular residence time of the nanovectors but their affinity to TfR was
      lower than whole antibodies. The ability of immunonanocapsules to specifically
      target cerebral tissues in addition to the promising features of LNC is of
      importance to the field of nanomedicine.

PMID- 18055057
TI  - Efficient delivery of siRNA using dendritic poly(L-lysine) for loss-of-function
      analysis.
AB  - RNA interference (RNAi) is a valuable tool for the validation of gene
      identification and functional genomics. Previously, it was reported that 6th
      generation dendritic poly(L-lysine) (KG6) transfected DNA into several cultivated
      cell lines with high efficiency and without any cytotoxic effects. In this study,
      the potential of KG6 to be an efficient siRNA carrier is investigated. KG6 showed
      effective knockdown of GAPDH with low cytotoxicity in combination with the weak
      base amphiphilic peptide, Endo-Porter. In addition, the knockdown of PEPCK, which
      is the rate-limiting enzyme for gluconeogenesis, led to a reduction in glucose
      production in rat hepatoma H4IIEC3 cells. Knockdown of organic cation transporter
      1 (OCT1), which is thought to be the gene that influences metformin action, was
      shown to successfully diminish the ability of metformin to inhibit
      gluconeogenesis in H4IIEC3 cells. In conclusion, using a combination of KG6 and
      Endo-Porter, a model system in which genes that influence metformin action can be
      identified was successfully constructed.

PMID- 18055058
TI  - Personality characteristics in adolescence predict long-term changes in body
      fatness.
AB  - Five personality characteristics were assessed in 312 adolescent boys and girls,
      and investigated in relation to the change in body fat percentage over 22 years
      of follow up. Boys with low levels of Social Inadequacy and girls with high
      levels of Recalcitrance showed relatively large gains in body fat percentage.

PMID- 18055059
TI  - Incidence and trends of childhood Type 1 diabetes in Croatia from 1995 to 2003.
AB  - AIMS/HYPOTHESIS: The aim of this study was to examine incidence and trends of
      Type 1 diabetes in children aged 0-14 years in Croatia from 1995 to 2003.
      METHODS: The incidence data were obtained from two sources. The incidence was
      calculated as the number of newly diagnosed Type 1 diabetes patients per 100,000
      person-years for the age group 0-14 years, and subgroups 0-4, 5-9, and 10-14
      years. Standardized incidence was calculated using the method of direct
      standardization to the world standard population for the age group 0-14 years.
      The ascertainment was estimated with capture-recapture method. Trends in the
      incidence of Type 1 diabetes for period from 1995 to 2003 in Croatia were
      analyzed using Poisson regression model. RESULTS: The standardized incidence of
      Type 1 diabetes for the whole age group was 8.87 per 100,000 person-years (95%
      CI: 5.07-12.68), for girls 8.47 (95% CI: 7.54-9.41) and for boys 9.26 (95% CI:
      8.30-10.21). During the studied period, the trend in incidence raised
      significantly for the whole age group (chi(2)=32.6, p<0.001). The average annual
      increase in incidence was 9% (95% CI: 5.8-12.2). CONCLUSIONS/INTERPRETATION: This
      rate of incidence places Croatia in a group of countries with moderate risk for
      development of Type 1 diabetes. The average annual increase in incidence of 9% is
      markedly higher than in most European countries, and probably reflects lifestyle
      changes upon economic recovery of the country.

PMID- 18055060
TI  - Drug delivery applications of supercritical fluid technology. Preface.

PMID- 18055061
TI  - Prognostic markers for stage I non-small cell lung cancer.

PMID- 18055062
TI  - Peripheral lung carcinoma: correlation of angiogenesis and first-pass perfusion
      parameters of 64-detector row CT.
AB  - PURPOSE: To investigate the value of 64-detector row CT first-pass perfusion
      imaging in the evaluation of tumor perfusion in patients with lung carcinoma, and
      to assess the correlation between the perfusion parameters and tumor
      angiogenesis. MATERIALS AND METHODS: Forty-six surgically peripheral lung
      carcinomas were examined with 64-detector row CT. First-pass CT perfusion study
      comprised of 12 repeated spiral acquisitions over 60s following a 50-ml
      intravenous bolus of contrast medium at 6-7 ml/s. Tumor specimens were assessed
      for microvessel density (MVD). Perfusion, peak enhancement intensity (PEI), time
      to peak (TTP), and blood volume (BV) and MVD of the tumor were compared by means
      of one-way ANOVA analysis of variance among histological type, size, metastasis
      and necrosis. Pearson correlation coefficients were conducted to represent the
      relationships between the perfusion parameters and MVD of the tumor. RESULTS:
      Mean values for perfusion, PEI, TTP, and BV of the 46 tumors were 70.3+/-39.4
      ml/min/ml, 67.0+/-37.6 HU, 36.9+/-11.2s, and 34.9+/-17.9 ml/100g, respectively.
      No statistically significant differences in perfusion parameters were found among
      different histological types (p>0.05). Considerable differences with higher
      perfusion, PEI and BV were noted in tumor < or = 3.0 cm than in tumor>3.0 cm
      (p<0.05). No statistically significant differences were found between nodule
      metastasis positive and negative groups (p>0.05). The necrotic tumors showed
      significantly lower perfusion, PEI and BV compared with non-necrotic tumors
      (p<0.05). Perfusion, PEI, and BV of the necrotic part manifested significantly
      lower, but TTP longer, than those of non-necrotic part of the necrotic tumors
      (p<0.05). Perfusion, PEI and BV were positively correlated with extent of MVD
      (r=0.715, 0.681, 0.762, respectively, all p<0.001), whereas no significant
      correlation was found between TTP and MVD (r=-0.154, p>0.05). CONCLUSION: 64
      detector row CT first-pass perfusion imaging is a valuable noninvasive method in
      evaluating tumor perfusion of peripheral lung carcinoma. CT perfusion parameters
      can be indicators for evaluating tumor necrosis and angiogenesis.

PMID- 18055063
TI  - Diagnosis of peripheral pulmonary lesions using a bronchoscope insertion guidance
      system combined with endobronchial ultrasonography with a guide sheath.
AB  - We developed a bronchoscope insertion guidance system that produces virtual
      images by extracting the bronchi by automatic threshold adjustment, and searching
      for the bronchial route to the determined target. We used this system in
      combination with a thin bronchoscope and endobronchial ultrasonography with a
      guide sheath (EBUS-GS), and evaluated its practicability, usefulness and safety.
      The subjects were 31 patients with 32 peripheral pulmonary lesions. Computed
      tomography (CT) data were transferred into this system, and virtual bronchial
      images were automatically produced by setting the lesion as the target. While
      virtual images with the target were displayed for comparison with real images by
      the system, a thin bronchoscope was advanced to the target bronchus.
      Transbronchial biopsy (TBB) was then performed by EBUS-GS. The system
      automatically produced virtual images to a median of fifth- (third- to seventh-)
      order bronchi. In all patients, the thin bronchoscope could be guided along the
      planned route, and observation to a median of fifth- (third- to seventh-) order
      bronchi was possible. Thirty lesions (93.8%) were successfully visualized by
      EBUS, and 27 (84.4%) could be pathologically diagnosed. In lesions < or =30mm in
      size, the EBUS visualization yield was 91.7% (22/24), and the diagnostic yield
      was 79.2% (19/24). The median total examination time was 22.3 (9.8-41.5) min. In
      summary, using the bronchoscope insertion guidance system, virtual images can be
      readily produced, and the bronchoscope can be successfully guided to the target.
      This method is promising as a routine examination method in the biopsy of
      peripheral pulmonary lesions.

PMID- 18055064
TI  - Endoscope drying/storage cabinet: interest and efficacy.
AB  - Inadequate drying of endoscope channels is a possible cause of microbial
      proliferation during storage. This risk could be reduced by any procedure or
      process used to dry endoscope channels and control storage conditions. The
      efficacy of a drying and storage cabinet (Hysis Medical) was tested on three
      different endoscopes: a colonoscope (Olympus); duodenoscope (Fujinon) and an
      enteroscope (Pentax), all of which had been artificially contaminated with a
      suspension of Pseudomonas aeruginosa CIP 103467. Changes to the residual internal
      contamination level of these endoscopes when stored inside or outside the drying
      cabinet for 12, 24, 48 or 72 h were compared. When stored in the drying and
      storage cabinet, microbial contamination levels on endoscopes were lower than the
      number of bacteria initially introduced and could decrease considerably
      thereafter. For endoscopes stored outside the drying storage cabinet, microbial
      numbers were stable or even increased. These data demonstrate the advantages of
      such endoscope drying/storage cabinets that limit the risk of bacterial
      proliferation in the internal channels of endoscopes during storage, and which
      ensure that the disinfection level reached at the end of the reprocessing
      procedure is maintained.

PMID- 18055065
TI  - Financial consequences of hospital-acquired bacteraemia in three Belgian
      hospitals in 2003 and 2004.
AB  - The financial and human costs of hospital-acquired infections are increasingly
      recognised in many healthcare systems. This study seeks to quantify excess
      expenditures on hospital-acquired bacteraemia (HAB) in three Belgian general
      hospitals in 2003 and 2004. Patients with HAB were compared with patients in the
      same All Patient Refined Diagnosis Related Groups (APR-DRGs) without HAB. Patient
      level costs were estimated using a hospital costing system developed by the
      'Universite Libre de Bruxelles', and compared with DRG-based funding for the
      three hospitals. HAB incidence was consistent with the national rate for two of
      the three hospitals, but considerably higher for the third. Both severity of
      illness and mortality were higher in the HAB group. Nosocomial bacteraemia was
      associated with an increased length of stay of 30 days and of 6.1 days in
      intensive care units. When compared with uninfected patients in the same DRG,
      treatment of HAB patients cost an additional euro 16,709. At current funding
      rates, hospitals made a mean profit of euro 446 for uninfected patients, but a
      mean loss of euro 2,431 for patients with HAB. Our findings suggest that
      hospitals have a financial interest in reducing the rate of HAB, even in a system
      which funds such complications through severity adjustments in the APR-DRG
      system. Growing international interest in pay for performance and other funding
      schemes will only strengthen these financial incentives.

PMID- 18055066
TI  - Pulmonary peptidergic innervation remodeling and development of airway
      hyperresponsiveness induced by RSV persistent infection.
AB  - Respiratory syncytial virus (RSV) infection causes bronchiolitis in infants and
      children, which is an important risk factor for the development of chronic
      asthma. To probe the underlying mechanisms that RSV infection increases the
      susceptibility of asthma, this present study was designed to establish a RSV
      persistent infection animal model by cyclophosphamide (CYP) pretreatment that
      more closely mimic human RSV infection. CYP is an immunosuppressant, which
      induced deficiency in cellular and humoral immunity. Pulmonary RSV titers, airway
      function and peptidergic innervation were measured on 7d, 28 d, 42 d and 60 d
      postinfection. The results showed that during RSV persistent infection, the lungs
      of RSV-inoculated animals pretreated with CYP showed higher RSV titers and
      exhibited obvious chronic inflammation. The results also showed that protein gene
      product 9.5 (PGP9.5), substance P (SP) and calcitonin gene-related peptide (CGRP)
      immunoreactive fibers increased and vasoactive intestinal peptide (VIP)
      immunoreactive fibers decreased during RSV persistent infection. These results
      demonstrate that RSV persistent infection induces significant alterations in the
      peptidergic innervation in the airways, which may be associated with the
      development of altered airway function.

PMID- 18055067
TI  - Neurosteroid modulation of GABAA receptors: molecular determinants and
      significance in health and disease.
AB  - Over the past 20 years it has become apparent that certain steroids, synthesised
      de novo in the brain, hence named neurosteroids, produce immediate changes
      (within seconds) in neuronal excitability, a time scale that precludes a genomic
      locus of action. Identified molecular targets underlying modulation of brain
      excitability include both the inhibitory GABA(A) and the excitatory NMDA
      receptor. Of particular interest is the interaction of certain neurosteroids with
      the GABA(A) receptor, the major inhibitory receptor in mammalian brain. During
      the last decade, compelling evidence has accrued to reveal that locally produced
      neurosteroids may selectively "fine tune" neuronal inhibition. A range of
      molecular mechanisms including the subunit composition of the receptor(s),
      phosphorylation and local steroid metabolism, underpin the region- and neuronal
      selectivity of action of neurosteroids at synaptic and extrasynaptic GABA(A)
      receptors. The relative contribution played by each of these mechanisms in a
      variety of physiological and pathophysiological scenarios is currently being
      scrutinised at a cellular and molecular level. However, it is not known how such
      mechanisms may act in concert to influence behavioural profiles in health and
      disease. An important question concerns the identification of the anatomical
      substrates mediating the repertoire of behaviours produced by neurosteroids.
      "Knock-in" mice expressing mutant GABA(A) subunits engineered to be insensitive
      to benzodiazepines or general anaesthetics have proved invaluable in evaluating
      the role of GABA(A) receptor subtypes in complex behaviours such as sedation,
      cognition and anxiety [Rudolph, U., Mohler, H., 2006. GABA-based therapeutic
      approaches: GABA(A) receptor subtype functions. Curr. Opin. Pharmacol. 6, 18-23].
      However, the development of a similar approach for neurosteroids has been
      hampered by the limited knowledge that, until recently, has surrounded the
      identity of the amino acid residues contributing to the neurosteroid binding
      pocket. Here, we will review recent progress in identifying the neurosteroid
      binding site on the GABA(A) receptor, and discuss how these discoveries will
      impact on our understanding of the role of neurosteroids in health and disease.

PMID- 18055068
TI  - Antitumor studies -- part 2: structure-activity relationship study for flavin
      analogs including investigations on their in vitro antitumor assay and docking
      simulation into protein tyrosine kinase.
AB  - Various analogs of flavins, 5-deazaflavins, and flavin-5-oxides were docked into
      the binding site of protein tyrosine kinase pp60(c-src), and some of them were
      assayed for their potential antitumor and PKC (protein kinase C) inhibitory
      activities in vitro. The results considering SAR (structure-activity
      relationship) revealed that the higher binding affinities obtained include
      compounds with the structure modifications on the flavin or 5-deazaflavin
      skeleton, namely, NH(2) or Ph (phenyl-) group at the C-2 position and so on.
      Computationally designed compounds 4a, 6a, b, 7, 11b, c, 12, 15, and 22c
      exhibited good docking results suggesting that they are potentially active
      antitumor agents. These compounds have 1-3 phenyl moieties, which are thought to
      be responsible for the planar aromatic fitting or electrostatic attraction onto
      the groove of the binding pocket.

PMID- 18055069
TI  - Should nurse academics engage in clinical practice?
AB  - The education of nurses has traditionally been conducted in the hospital based
      setting. This changed over the last few decades, with nursing education now being
      a tertiary based course in many countries. There were numerous reasons for this
      move, the main goal being to improve the educational experience of students and
      thus the competence of graduates. Nurse academics whose role is to educate
      students are faced with the challenge of ensuring their teaching reflects the
      contemporary nursing environment. One way of doing this is by actively engaging
      in clinical practice. However there are arguments for and against (as well as
      barriers to) them doing so and little empirical evidence to support either
      argument. Individually, nurse academics must make a decision about whether
      engaging in clinical practice is beneficial to their career and the students they
      teach.

PMID- 18055070
TI  - Evaluation of protective immunity of Leptospira immunoglobulin like protein A
      (LigA) DNA vaccine against challenge in hamsters.
AB  - We demonstrated earlier that immunization with recombinant Leptospira
      immunoglobulin like protein A (LigA) induced significant protection against
      virulent Leptospira interrogans serovar Pomona challenge in hamsters. However,
      the protective immune mechanism remains unclear. In the present study we
      demonstrated the protective efficacy of a LigA DNA vaccine and evaluated the
      immune mechanism underlying the protection against leptospirosis in hamsters. The
      LigA DNA vaccine was constructed in two truncated forms as the conserved portion
      (LigAcon) and a variable portion (LigAvar). Four-week-old hamsters were immunized
      three times at two-week intervals with vector alone or an equal amount of a
      recombinant construct containing either LigAcon or LigAvar. All animals were
      challenged intraperitoneally 2 weeks after the last immunization with a dose
      (LD50=10(8)) of virulent L. interrogans serovar Pomona. Prior to challenge, four
      animals were sacrificed, the spleen was removed aseptically, and splenocytes were
      assayed for lymphocyte proliferation and cytokine profiles in response to recall
      antigen. The protective efficacy was evaluated on the basis of survival and
      histopathological lesions in the kidney. The immuno-protective mechanism was
      assessed on the basis of Th1/Th2 profile of cytokines in immunized animals. Our
      results indicate that immunization with LigA DNA vaccine provides significant
      protection against leptospirosis. We suggest that immuno-protection is conferred
      by both humoral and cellular immunity as revealed by an increase in antibody
      titers during subsequent boosters, significant proliferation of lymphocytes and
      enhancement of both Th1 and Th2 cytokines. Taken together, the present study
      suggests that a LigA DNA vaccine is a promising candidate for prevention of
      leptospirosis.

PMID- 18055071
TI  - Safety and immunogenicity of a live-attenuated auxotrophic candidate vaccine
      against the intracellular pathogen Rhodococcus equi.
AB  - Rhodococcus equi causes serious pneumonia in neonatal foals and is an
      opportunistic pathogen of people with compromised cellular immunity. No effective
      vaccine against R. equi disease in foals is available. We tested the safety and
      immunogenicity of a live, fully attenuated riboflavin auxotrophic candidate
      vaccine strain of R. equi (R. equi rib-). We demonstrated that R. equi rib- is
      immunogenic and capable of inducing IFN-gamma responses in immunocompetent BALB/c
      mice, yet it is safe even in an immunocompromised SCID mouse infection model.
      Moreover, it protects immunocompetent mice against virulent R. equi challenge. In
      foals, R. equi rib- was likewise safe and stimulated serum R. equi-specific
      immune responses. A preliminary immunization strategy did not afford protection
      against virulent R. equi challenge and therefore, optimization of the vaccine
      formulation and or vaccination protocol will be necessary.

PMID- 18055072
TI  - Safety and immunogenicity of cytotoxic T-lymphocyte poly-epitope, DNA plasmid (EP
      HIV-1090) vaccine in healthy, human immunodeficiency virus type 1 (HIV-1)
      uninfected adults.
AB  - We evaluated EP HIV-1090 vaccine, a DNA plasmid encoding 21 cytotoxic T
      lymphocyte (CTL) epitopes of human immunodeficiency virus type 1 (HIV-1) and the
      pan-DR helper T-lymphocyte epitope (PADRE), in a dose escalation, randomized,
      double-blinded, placebo-controlled Phase 1 trial. Vaccine, at 0.5, 2.0, or 4.0mg
      doses, or placebo was injected four times over 6 months. Forty-two healthy, HIV-1
      uninfected adults were enrolled. Using an interferon-gamma ELISPOT assay, a
      response to PADRE was detected in one vaccine recipient. Three vaccine recipients
      raised anti-HIV-1 CD8+ CTL measured by chromium-release assay. The vaccine was
      safe and well-tolerated, but only weakly immunogenic.

PMID- 18055073
TI  - Evidence for enhanced central memory priming by live Mycobacterium bovis BCG
      vaccine in comparison with killed BCG formulations.
AB  - Development of cattle vaccines against bovine tuberculosis is a GB research
      priority. Recently, it has been shown that formalin-killed Bacille Calmette
      Guerin (BCG) delivered with the liposomal adjuvant NAX687 imparted significant
      protection against Mycobacterium bovis infection in the guinea pig aerosol
      infection model. Extending these studies, we inoculated calves with live BCG,
      formalin-killed BCG and formalin-killed BCG formulated in NAX687. Live and killed
      BCG vaccine formulations induced primary effector T-cell populations comparably,
      both killed BCG formulations also induced potent humoral immune responses. In
      contrast, live BCG generated enhanced central memory responses against the
      protective antigen Ag85A whilst killed BCG-induced such responses only poorly.
      However, the poor capacity of killed BCG to generate central memory could be
      partially overcome by formulation with NAX687. Measurement of central memory
      responses induced by TB vaccine candidates in cattle may provide a useful
      correlate of protection and warrants further investigation in challenge
      experiments.

PMID- 18055074
TI  - Vectors encoding carcinoembryonic antigen fused to the B subunit of heat-labile
      enterotoxin elicit antigen-specific immune responses and antitumor effects.
AB  - Vectors encoding CEA fused to the A (CEA-LTA) or B (CEA-LTB) subunits of the heat
      labile enterotoxin were constructed and their immunogenicity was compared. The
      CEA-LTB fusion was shown to elicit a greater CEA-specific antibody and CD8+ T
      cell response. Plasmid DNA and Adenovirus vectors encoding CEA-LTB proved to be
      immunogenic in CEA transgenic (CEA.tg) mice. CEA.tg mice immunized with repeated
      injections of plasmid pV1J/CEA-LTB followed by Ad/CEA-LTB were protected from
      tumor growth, but the adjuvant activity of the LTB protein was lost upon mutation
      of the LTB sequence. Depletion of T-regulatory cells increased the vaccine
      antitumor effect. Tumor protection was abrogated if the NK or CD8+ cell
      population was depleted before tumor challenge. Passive transfer studies
      demonstrated that CD8+ T cells contribute to the antitumor effect, thus
      suggesting that a genetic vaccine based on plasmid DNA and adenoviral vectors
      encoding CEA-LTB augments CEA-specific immune responses and significantly
      protects from tumor development.

PMID- 18055075
TI  - Cost-effectiveness of quadrivalent human papillomavirus (HPV) vaccination in
      Mexico: a transmission dynamic model-based evaluation.
AB  - We examined the potential health outcomes and cost-effectiveness of quadrivalent
      human papillomavirus (HPV) 6/11/16/18 vaccination strategies in the Mexican
      population using a multi-HPV type dynamic transmission model. Assuming similar
      cervical screening practices, with or without vaccination, we examined the
      incremental cost-effectiveness of vaccination strategies for 12 year-old females,
      with or without male vaccination, and temporary age 12-24 catch-up vaccination
      for females or both sexes. The most effective strategy therein was vaccination of
      12-year-olds, plus a temporary 12-24-year-old catch-up program covering both
      sexes; whereby HPV 6/11/16/18-related cervical cancer, high-grade cervical
      precancer, and genital wart incidence was reduced by 84-98% during year 50
      following vaccine introduction. Incremental cost-effectiveness ratios in the
      primary analyses ranged from approximately 3000 dollars (U.S.) per quality
      adjusted life year (QALY) gained for female vaccination strategies to
      approximately 16000 dollars /QALY for adding male vaccination with catch-up.

PMID- 18055077
TI  - Role and influence of mycorrhizal fungi on radiocesium accumulation by plants.
AB  - This review summarizes current knowledge on the contribution of mycorrhizal fungi
      to radiocesium immobilization and plant accumulation. These root symbionts
      develop extended hyphae in soils and readily contribute to the soil-to-plant
      transfer of some nutrients. Available data show that ecto-mycorrhizal (ECM) fungi
      can accumulate high concentration of radiocesium in their extraradical phase
      while radiocesium uptake and accumulation by arbuscular mycorrhizal (AM) fungi is
      limited. Yet, both ECM and AM fungi can transport radiocesium to their host
      plants, but this transport is low. In addition, mycorrhizal fungi could thus
      either store radiocesium in their intraradical phase or limit its root-to-shoot
      translocation. The review discusses the impact of soil characteristics, and
      fungal and plant transporters on radiocesium uptake and accumulation in plants,
      as well as the potential role of mycorrhizal fungi in phytoremediation
      strategies.

PMID- 18055078
TI  - On seasonal variations of radiocesium speciation in the surface sediments of Lake
      Juodis, Lithuania.
AB  - Data on radiocesium speciation measured seasonally in black silt surface
      sediments in the shallow terrace and in the deepest southern part of Lake Juodis
      (Lithuania) in 2004-2005 are presented. It is shown that seasonal variations of
      radiocesium exchangeable fractions in the sediments in the shallow terrace are
      mainly related to its redistribution due to the vital cycle of green algae
      covering bottom surfaces - processes of their growth and decomposition. A
      seasonal course of those fractions in surface sediments of the deepest bottom
      areas of the lake follows a distinct pattern and is annually recycling. It is
      maximum in winter and declines due to stagnant bottom water zone disruption in
      summer. It is shown that surface sediments in the deepest bottom areas of the
      lake are not a radiocesium source during the formation of the anaerobic zone in
      bottom water in winter, and act in that case as its acceptor. The radiocesium
      remobilization to the bottom water is seasonal and site-specific. It is suggested
      to be due to three main processes: its diffusion from deeper and more active
      sediments, its redistribution during decomposition of organics freshly
      accumulated in surface sediments and a radiocesium flux induced by the mechanism
      of the seasonal anaerobic zone formation in near-bottom water.

PMID- 18055079
TI  - Organohalogen pollutants in herring from the northern Baltic Sea: concentrations,
      congener profiles and explanatory factors.
AB  - Organohalogen contaminants were investigated in Baltic herring caught from three
      catchment areas in the Baltic Sea, off the coasts of Finland. Pools of both small
      and large herring were analysed for polychlorinated biphenyls (PCB), dibenzo-p
      dioxins, dibenzofurans, naphthalenes, camphenes (toxaphene), polybrominated
      diphenyl ethers and the pesticide DDT and its metabolites. PCB concentrations per
      fresh weight in small herring were at the same level in all catchment areas, i.e.
      the Bothnian Bay, the Bothnian Sea and the Gulf of Finland, revealing no hot
      spots and reflecting most likely long term emissions and atmospheric deposition.
      Differences in the levels and/or congener profiles of other contaminants between
      catchment areas may be explained by point sources. Similar concentrations in
      small and large herring in the Gulf of Finland were possibly due to their common
      nutrition. In the other areas, differences between small and large herring most
      likely reflected their different food sources.

PMID- 18055080
TI  - The relative efficacy of bona fide psychotherapies for treating post-traumatic
      stress disorder: a meta-analysis of direct comparisons.
AB  - Psychotherapy has been found to be an effective treatment of post-traumatic
      stress disorder (PTSD), but meta-analyses have yielded inconsistent results on
      relative efficacy of psychotherapies in the treatment of PTSD. The present meta
      analysis controlled for potential confounds in previous PTSD meta-analyses by
      including only bona fide psychotherapies, avoiding categorization of
      psychotherapy treatments, and using direct comparison studies only. The primary
      analysis revealed that effect sizes were homogenously distributed around zero for
      measures of PTSD symptomology, and for all measures of psychological functioning,
      indicating that there were no differences between psychotherapies. Additionally,
      the upper bound of the true effect size between PTSD psychotherapies was quite
      small. The results suggest that despite strong evidence of psychotherapy
      efficaciousness vis-a-vis no treatment or common factor controls, bona fide
      psychotherapies produce equivalent benefits for patients with PTSD.

PMID- 18055081
TI  - The origins of public concern with taconite and human health: Reserve Mining and
      the asbestos case.
AB  - Asbestos first became an issue to Minnesota's iron industry when it was revealed
      that mineral fibers similar to those in Reserve Mining's tailings were being
      found in drinking water for several communities that used Lake Superior as their
      primary water source. This discovery turned what had largely been an
      environmental court battle into a case concerning public health. The courts
      listened to much conflicting and uncertain scientific testimony on the size and
      distribution of the mineral fibers and on the potential health effects imposed by
      them. In April 1974, the plant was ordered to shut down by a federal judge but
      the company quickly appealed the decision. The appeals court granted a stay and
      ultimately ruled that the plant's closure could not be justified based on the
      unknown health effects of the mineral fibers since the consequences of such an
      action would have immediate and severe social and economic impacts. The plant was
      allowed to continue operation, but ordered to abate emissions to air around the
      plant and to switch to a land-based tailings disposal system. Much of the
      scientific uncertainty and public concern over mineral fibers in Minnesota's
      taconite industry remain today.

PMID- 18055082
TI  - Protective effects of olanzapine and haloperidol on serum withdrawal-induced
      apoptosis in SH-SY5Y cells.
AB  - PURPOSE: Recent clinical studies have suggested that treatment with second
      generation antipsychotic drugs such as olanzapine may prevent progressive
      alterations of brain structure in patients with schizophrenia. However, the
      molecular mechanisms underlying these different effects remain to be determined.
      We investigated the mechanisms of action of olanzapine and haloperidol, on serum
      withdrawal apoptosis in human neuroblastoma SH-SY5Y cells. METHODS: SH-SY5Y cells
      were cultured with olanzapine and haloperidol in medium with or without serum. We
      determined the effects of the drugs on cell viability against serum withdrawal by
      3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay.
      Additionally, to explore the drugs' actions, Western blot was performed to
      examine the expression of key genes involved in GSK-3beta-mediated signaling,
      notably GSK-3beta, beta-catenin, and Bcl-2. RESULTS: SH-SY5Y cells suffered about
      a 38% loss in cell number under serum-free conditions for 48 h. Olanzapine (10
      200 muM) up to 100 muM significantly attenuated serum withdrawal-induced cell
      loss (p<0.01), and a dose of 100 muM also increased cell viability (p<0.05). In
      contrast, haloperidol (0.01-10 muM) did not affect cell viability but exacerbated
      cell death at 10 muM under serum-free conditions (p<0.01). Western blot analysis
      showed that olanzapine, but not haloperidol, prevented the serum withdrawal
      induced decrease in levels of neuroprotective proteins such as p-GSK-3beta, beta
      catenin, and Bcl-2 (p<0.01), whereas haloperidol robustly reduced the levels of
      these proteins at a 10 muM dose in serum-starved cells (p<0.05). Moreover,
      olanzapine alone significantly increased phosphorylation of GSK-3beta under
      normal conditions (p<0.05). CONCLUSIONS: This study showed that olanzapine may
      have neuroprotective effects, whereas haloperidol was apparently neurotoxic. The
      actions of signaling systems associated with GSK-3beta may be key targets for
      olanzapine and haloperidol, but their effects are distinct. These differences
      suggest different therapeutic effects of first and second generation
      antipsychotic drugs in patients with schizophrenia.

PMID- 18055083
TI  - Effects of divalproex on disruptive behavior of jail inmates.

PMID- 18055084
TI  - Platelet serotonin concentration and suicidal behavior in combat related
      posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) is a serious and global problem, a
      psychiatric disorder that frequently occurs with different comorbidities, and is
      associated with a high suicide rate. Pathophysiologically, both PTSD and suicidal
      behavior are related to disturbances in the central serotonergic system.
      Serotonin (5-hydroxytryptamine, 5-HT) controls emotional behavior, anxiety,
      impulsivity and aggression, and nearly all known antidepressants and antianxiety
      drugs affect 5-HT transmission. Platelet 5-HT can be used as a limited peripheral
      marker of the central serotonergic synaptosomes, since it is related to
      particular basic psychopathological characteristics of several psychiatric
      disorders. Platelet 5-HT concentration has been reported to be similar in PTSD
      subjects and healthy controls, but suicidal patients across different psychiatric
      diagnoses have reduced platelet 5-HT concentration. This study examined platelet
      5-HT concentration by the spectrofluorimetric method in male subjects: 73
      suicidal and 47 non-suicidal veterans with current and chronic combat related
      PTSD, 45 suicidal and 30 non-suicidal comparative non-PTSD subjects and 147
      healthy men. The presence of suicidal behavior (score=0, non-suicidal; scores >
      or =1, suicidal) was assessed with the Hamilton Depression Rating Scale-17
      (HDRS). Platelet 5-HT concentration was significantly lower in suicidal PTSD and
      non-PTSD patients compared to non-suicidal patients or healthy controls. Since
      the majority of patients scored very low on item 3 of HDRS, no significant
      correlation between suicidal scores and platelet 5-HT concentration was found.
      These results show that reduced platelet 5-HT concentration is related to
      suicidal behavior in PTSD, and suggest that platelet 5-HT concentration might be
      used as a peripheral marker to predict suicidal behavior across psychiatric
      diagnoses.

PMID- 18055085
TI  - Indications of hepatic and cardiac toxicity caused by subchronic Tricholoma
      flavovirens consumption.
AB  - The yellow tricholoma (Tricholoma flavovirens or Tricholoma equestre) is a wild
      mushroom species that was previously considered edible and tasty. Recently, it
      caused several cases of delayed rhabdomyolysis in humans and elevated serum
      creatine kinase (CK) activities in laboratory mice (Mus musculus) in a dose
      response study. The present study continued to examine the effects of prolonged
      T. flavovirens consumption at 12 g freshly frozen mushroom kg(-1)d(-1) on the
      plasma clinical chemistry and organ histology of mice. The plasma CK and CK-MB
      activities and the plasma bilirubin concentrations were higher in the exposed
      mice than in the controls. In addition, pericardial lymphocyte infiltrates were
      present in the mice that had consumed the mushroom. The results indicate myo-,
      cardio- and hepatotoxic effects of T. flavovirens.

PMID- 18055086
TI  - [Radiological evaluation after lipomodelling for correction of breast
      conservative treatment sequelae].
AB  - Breast lipomodelling has been used in our unit since 2002 to correct the sequelae
      of conservative treatment of cancer. Morphologically, satisfactory results have
      been recorded and the method is likely to develop considerably. However, the
      technique has also been questioned because of the possible deleterious
      radiological impact of injecting fat into the breast. The present work
      investigated the radiological aspect of conserved breast reconstructed by
      lipomodelling in a series of 21 patients undergoing ultrasound examination,
      mammography and MRI, before and after the procedure. Benign-looking
      microcalcifications were detected on 19% of the mammographies, small (<1cm) oily
      cysts and complex cysts were visible on respectively 57 and 19% of ultrasound
      images, whereas 47% of the MRI scans indicated cytosteatonecrotic lesions. Even
      though multiple events could be observed, their frequency is close to that
      observed following other conventional breast surgery. Besides, there is clear
      radiological evidence of benignity. The conclusion of the study is that images
      obtained after lipomodelling are satisfactory and in no way suggestive of
      recurrence of breast cancer. Provided that radiologists and experts are aware of
      this pattern, there is no impact on the radiological follow-up of the patients.

PMID- 18055087
TI  - [Free-flap reconstruction in the elderly patient].
AB  - The objective of the study was to evaluate the safety and the efficacity of
      microsurgery in the elderly patient population. Between 2003 and 2005, 10 free
      flaps were performed in 10 patients who were aged 70 years or older. One flap
      underwent reexploration, for an overall success rate of 100%. Medical
      complications in the postoperative period were further evaluated. Effects of
      American Society of Anesthesiologists (ASA) status, operation time, and age on
      complication rate were evaluated. Only ASA status was significant for the
      occurrence of postoperative medical complications; class 3 and 4 patients were at
      higher risk than class 1 and 2. Neither operation time nor age was predictive of
      postoperative complications. Microvascular free-tissue transfer is a safe and
      reliable option in the elderly population. The success rate of free-flaps is not
      different from that for other age groups. The rate of postoperative medical
      complications was 20%: most complications were in ASA class 3 and 4 patients.

PMID- 18055088
TI  - [Solitary subcutaneous hydatid cyst of gluteal area: an unusual localisation. A
      case report].
AB  - Subcutaneous localization of hydatid cyst is uncommon even in endemic zone.
      Symptoms are often discrete. Diagnosis is confirmed by imaging: ultrasonography
      and/or magnetic resonance imaging, thus avoiding any untimely gesture. The
      treatment is surgery. Authors report a case of unusual subcutaneous localization
      of solitary hydatid cystis in the gluteal area.

PMID- 18055089
TI  - [Prophylactic mastectomies and immediate breast reconstruction in patients at
      very high genetic risk: our experience with 14 cases].
AB  - AIMS: Prophylactic mastectomy has been the subject of major publications by
      international groups. Its oncology benefit is undisputed in patients with a
      genetic mutation. Nevertheless, its impact on quality of life, its psychological,
      esthetic, sexual, functional and pain repercussions are such that it should not
      and must never be programmed in an emergency situation. We report our experience
      with 14 patients at very high genetic risk having undergone a bilateral
      prophylactic mastectomy with immediate breast reconstructive surgery. METHODS:
      From 1 March 2001 to 31 March 2006, 14 patients at very high genetic risk, seven
      of whom had a history of breast cancer, underwent immediate breast reconstruction
      with skin sparing mastectomy and preservation of the nipple-areolar complex.
      RESULTS: In 71.5% of the cases, we obtained a definitive conservation of the
      nipple-areolar complex, with esthetic results judged very satisfying. CONCLUSION:
      Immediate bilateral breast reconstruction by provisional or definitive implant
      with conservation of the skin flap and the nipple-areolar complex may constitute
      a positive radical issue for requesting and motivated patients at high genetic
      risk, managed by a multidisciplinary team.

PMID- 18055090
TI  - Seroma treatment after dermo-lipectomy.
AB  - We can consider the seroma as a rather common complication in abdominal dermo
      lipectomy surgery. In our case, the possibility has arisen to successfully reduce
      a remarkable accumulation of liquid using a simple but efficient protocol
      consisting on cortisone infiltrations.

PMID- 18055092
TI  - Synaptosomal GABA uptake decreases in paraoxon-treated rat brain.
AB  - A synaptosomal model was used to evaluate in vivo effects of paraoxon on the
      uptake of [(3)H]GABA in rat cerebral cortex and hippocampus. Male Wistar rats
      were given a single intraperitoneal injection of one of three doses of paraoxon
      (0.1, 0.3, or 0.7 mg/kg) and acetylcholinesterase (AChE) activity in the plasma,
      cerebral cortex, and hippocampus was measured at 30 min, 4h, and 18 h after
      exposure. [(3)H]GABA uptake in synaptosomes was also studied in another series of
      animals. Paraoxon administration (0.3 and 0.7 mg/kg) caused significant
      inhibition of AChE activity in the plasma and both brain areas at all time
      points. 0.1 mg/kg paraoxon significantly inhibited AChE activity but only in the
      plasma for 4h, the activity was completely recovered at 18 h. GABA uptake was
      significantly (p<0.001) reduced in both cerebral cortex (18-32%) and hippocampal
      (16-23%) synaptosomes at all three time points after administering 0.7 mg/kg of
      paraoxon, a dose that seems to be sufficient to induce seizure activity. L-DABA,
      an inhibitor of neuronal GABA transporter, allowed us to conclude that the uptake
      was mediated primarily by neuronal GABA transporter GAT-1. In conclusion, present
      data suggests that GABA uptake by synaptosomes decreases probably secondary to
      paraoxon-induced seizure activity.

PMID- 18055091
TI  - Drug metabolism enzyme expression and activity in primary cultures of human
      proximal tubular cells.
AB  - We previously catalogued expression and activity of organic anion and cation,
      amino acid, and peptide transporters in primary cultures of human proximal
      tubular (hPT) cells to establish them as a cellular model to study drug transport
      in the human kidney [Lash, L.H., Putt, D.A., Cai, H., 2006. Membrane transport
      function in primary cultures of human proximal tubular cells. Toxicology 228, 200
      218]. Here, we extend our analysis to drug metabolism enzymes. Expression of 11
      cytochrome P450 (CYP) enzymes was determined with specific antibodies. CYP1B1,
      CYP3A4, and CYP4A11 were the only CYP enzymes readily detected in total cell
      extracts. These same CYP enzymes, as well as CYP3A5 and possibly CYP2D6, were
      detected in microsomes from confluent hPT cells, although expression levels
      varied among kidney samples. In agreement with Western blot data, only activity
      of CYP3A4/5 was detected among the enzyme activities measured. Expression of all
      three glutathione S-transferases (GSTs) known to be found in hPT cells, GSTA,
      GSTP, and GSTT, was readily detected. Variable expression of three
      sulfotransferases (SULTs), SULT1A3, SULT1E, and SULT2A1, and three UDP
      glucuronosyltransferases (UGTs), UGT1A1, UGT1A6, and UGT2B7, was also detected.
      When examined over the course of cell growth to confluence, expression of all
      enzymes was generally maintained at readily measurable levels, although they were
      often lower than in fresh tissue. These results indicate that primary cultures of
      hPT cells possess significant capacity to metabolize many classes of drugs, and
      can be used as an effective model to study drug metabolism.

PMID- 18055093
TI  - Reconstitution of immunodeficient SCID/beige mice with human cells: applications
      in preclinical studies.
AB  - Experimental studies of the in vivo behaviour of human cells and tissues have
      become possible with the development of immunodeficient mice strains. Such mice
      accept readily allogeneic or xenogeneic grafts, including grafts of human cells
      or tissues, without rejection. In this review we describe different
      immunodeficient mouse strains that have been used for reconstitution by human
      immune cells. We subsequently go through the experience that we and others have
      had with reconstitution, and mention the adverse effects, in particular
      xenogeneic graft versus host reactions. The use of haematopoietic stem cells
      avoids such reactions but the immunological reconstitution may take several
      months. We then report the use of immunodeficient mice for the study of chronic
      vascular rejection of human mesenteric arteries due to cellular or humoral
      alloreaction. We have shown that SCID/beige mice grafted with a human artery at
      the place of the aorta developed a thickening of the intima of the human artery
      after 5-6 weeks, when they were reconstituted with spleen cells from another
      human donor. The thickening is mainly due to a proliferation of smooth muscle
      cells. The same type of lesion developed if they received injection of antibodies
      towards HLA class I antigens. The arteries of the mouse did not develop any
      lesion. The arterial lesions closely resembled those seen after clinical organ
      transplantation. Mice that received spleen cells from the same human donor
      developed little or no lesions. An important aspect of this experimental
      transplantation model is the possibility to test drugs that may be used in
      clinical transplantation. In recent experiments we have shown that novel
      immunosuppressive drugs can inhibit the hyperproliferation of smooth muscle cells
      in vitro. Preclinical testing in reconstituted SCID/beige mice grafted with human
      arteries will permit the evaluation of the potential use of these drugs to
      prevent chronic vascular rejection. The model also allows pharmacodynamic studies
      that give information on the biological impact of different drugs that may be
      used in experimental or clinical transplantation.

PMID- 18055094
TI  - Financial strain is a significant correlate of sleep continuity disturbances in
      late-life.
AB  - Although psychological stress has been associated with disturbed sleep in younger
      populations, little is known about the stress-sleep relationship in late-life. In
      the present study, we evaluated relationships among a chronic stressor, ongoing
      financial strain, and sleep in a heterogenous sample (n=75) of community-dwelling
      elders (mean age=74.0 years). Self-report measures included ongoing financial
      strain, mental health, physical health and subjective sleep quality. Sleep
      duration, continuity, and architecture were measured by polysomnography (PSG).
      Analysis of variance and regression were used to test the hypothesis that ongoing
      financial strain is a significant correlate of disturbed sleep in the elderly.
      Covariates included age, sex, mental health and physical health. Analyses
      revealed that ongoing financial strain is a significant correlate of PSG-assessed
      sleep latency, wakefulness after sleep onset, and sleep efficiency. After
      adjusting for the effects of age, sex, mental health, and physical health on
      sleep, ongoing financial strain was associated with lower sleep efficiency
      (p<.01). Our results show that chronic stress, as measured by ongoing financial
      strain, is a significant correlate of sleep disturbances in the elderly, even
      after adjusting for factors known to impact sleep in late-life.

PMID- 18055095
TI  - Early onset vulvar Lichen Sclerosus in premenopausal women and oral
      contraceptives.
AB  - OBJECTIVE: For vulvar Lichen sclerosus (LS) immunological factors, genetic
      predisposition, and decreased 5 alpha-reductase activity have been discussed as
      aetiological factors. During the last decade an increase of LS in young women has
      been suspected. Aim of this study was to evaluate data of premenopausal women
      with early onset LS to find potential risk factors focussing on the use of oral
      contraceptives. STUDY DESIGN: We retrospectively analyzed the data of 40
      premenopausal patients with early onset LS regarding use of oral contraceptives
      (OCPs), and first occurrence of LS. To compare these data in a case-control study
      we analyzed a matched control group of 110 healthy women. RESULTS: All our LS
      patients were using OCPs compared to 73 women (66.4%) in the control group. OCPs
      with anti-androgenic activity (chlormadinone acetate, cyproterone acetate,
      dienogest, and drospirenone) were used by 28 (70%) of the LS patients and by 35
      (47.9%) of the 73 women using OCPs in the control group. Thus, the odds ratio for
      early onset LS for women using anti-androgenic OCPs was 2.53 (95% CI: 1.12-5.75).
      CONCLUSION: Our data suggest that disturbance of the androgen dependent growth of
      the vulvar skin by OCPs and especially by OCPs with anti-androgenic properties
      might trigger the early onset of LS in a subgroup of susceptible young women.

PMID- 18055096
TI  - Electronic and vibrational polarizabilities of the twenty naturally occurring
      amino acids.
AB  - The geometries, relative energies, gas-phase static and dynamic dipole
      polarizabilities of the two most stable neutral forms and of the zwitterionic
      form of the twenty naturally occurring amino acids have been obtained by Density
      Functional and conventional ab initio Hatree-Fock theories using correlation
      consistent basis sets. Mean electronic polarizabilities (<alpha(e)>s) are
      encompassed in the 40-160 a.u. range and are little dependent on the amino acid
      framework conformation and structure. The relation between <alpha(e)> and the
      number of electrons in the molecule makes to classify the amino acids as one of
      the most polarizable family of compounds. Calculated <alpha(e)> values of the
      neutral forms linearly relate to the molecular volume and molecular hardness as
      well as, rather unexpectedly, with the experimental values in water solution,
      where amino acids are known to be in a zwitterionic form. Vibrational
      polarizabilities amount to 15-45 a.u.. They come essentially from the low
      frequency angular deformation modes of the -OH and -NH(2) groups.

PMID- 18055097
TI  - Predicting fetal growth restriction with renal volume using 3-D ultrasound:
      efficacy evaluation.
AB  - Early detection and management of fetal growth restriction (FGR) is very
      important in prenatal care and daily practice, because FGR fetuses may suffer
      increased risk of perinatal morbidity and mortality. Renal volume (RV) might be
      one of the important parameters of fetal growth. Yet, no prenatal assessment of
      fetal RV in FGR fetuses by 3-D ultrasound (US) has been reported. We undertook a
      prospective and cross-sectional study using quantitative 3-D US to assess the
      efficacy of fetal RV in predicting FGR. All fetuses were singletons and were
      followed-up to delivery to determine whether they had FGR complications. In
      total, 221 fetuses without FGR and 28 fetuses with FGR were included. Our results
      showed fetal RV assessed by 3-D US can differentiate fetuses with FGR from
      fetuses without FGR. The best predicting threshold for FGR is at the tenth
      percentile of fetal RV. Using the tenth percentile as the cutoff, the efficacy of
      fetal RV in predicting FGR was sensitivity 96.4%, specificity 95.9%, positive
      predictive value 75.0%, negative predictive value 99.5% and accuracy 96.0%,
      respectively. Fetal RV assessed by 3-D US can be applied to detect FGR
      prenatally. We believe fetal RV assessment using 3-D US is a useful test in
      detecting fetuses with FGR.

PMID- 18055098
TI  - High frequency ultrasound prediction of mechanical properties of cortical bone
      with varying amount of mineral content.
AB  - In this study, we evaluate if high frequency ultrasound impedance measurements
      can predict the mechanical properties of bones where the amount of bone mineral
      is varied. The motivation stems from the potential utility of ultrasound as a
      noninvasive technique to evaluate and monitor the mechanical properties of bone
      during treatment of diseased states where the ratio of mineral content to organic
      matrix content could change (e.g., metabolic bone diseases, osteoarthritis,
      osteogenesis imperfecta, fracture healing). Eleven cortical bovine femur samples,
      which were taken along the long axis of femur, were used in each group. Bone
      samples with reduced mineral content (estimated to be 21% and 35% less than the
      control) were obtained by immersing samples into fluoride ion solution for 3 and
      12 d. Control and fluoride treated samples were first tested mechanically in
      tension. Acoustic impedances of the mechanically tested samples were obtained by
      using scanning acoustic microscopy (SAM). Results from mechanical tests indicate
      that the tensile elastic modulus of the samples was highly correlated to the
      yield strength (r(2) = 0.94, p < 0.01) and to the ultimate strength (r(2) = 0.75,
      p < 0.01). SAM results indicate that the acoustic impedances were significantly
      correlated to the elastic modulus (r(2) = 0.85, p < 0.01), yield strength (r(2) =
      0.86, p < 0.01) and ultimate strength (r(2) = 0.70, p < 0.01). These results show
      that ultrasonic techniques could potentially be used to predict the in vivo
      ultimate strength of bone tissue caused by changes in mineral content.

PMID- 18055099
TI  - Dual-mode ultrasound transducer for image-guided interstitial thermal therapy.
AB  - Deep-seated tumors can be treated by minimally invasive interstitial ultrasound
      thermal therapy. A miniature transducer emitting high-intensity acoustic waves is
      placed in contact with the targeted area to induce local thermal necrosis.
      Accurate positioning of the probe and treatment monitoring must be achieved for
      the technique to be effective. A piezocomposite technology was used for obtaining
      both high-quality imaging and effective treatment with the same transducer.
      Prototypes were designed and built to be compatible with an endoscopic approach
      for treating cholangiocarcinomas in the biliary ducts. The transducer had
      dimensions of 2.5 x 7.5 mm(2), it was cylindrically focused at 10 mm and it was
      operated at a center frequency of 11 MHz. Transducer efficiency was measured at
      71%, and the impulse response corresponded to an axial resolution of 0.2 mm. In
      vitro tests were conducted on samples of pig liver in which lesions up to 10 mm
      in depth were induced. B-mode images were obtained by mechanically rotating the
      transducer. Treatments were monitored in three ways: (i) classical M-mode images,
      (ii) images of local deformation of ultrasound lines during heating and (iii)
      comparison of the displacements induced in the tissue by radiation force, before
      and after treatments. The successful use of piezocomposite materials to
      manufacture dual-mode transducers opens new perspectives for interstitial
      ultrasound thermal therapy.

PMID- 18055100
TI  - Tacrolimus-related polyneuropathy: case report and review of the literature.
AB  - Patients, in particular recipients of orthotopic liver transplants, receiving the
      immunosuppressant tacrolimus (FK-506), are at risk for developing central
      neurotoxic adverse events. We report the occurrence of a tacrolimus-induced
      peripheral neurotoxic event, i.e. pure motor axonal polyneuropathy of the lower
      limbs in a 44-year-old woman, 9 days after combined orthotopic liver and pancreas
      transplantation. She was treated for 5 days with intravenous immunoglobulins.
      Partial recovery followed over months to years. An overview of all 11 reported
      FK506-associated polyneuropathies is given.

PMID- 18055101
TI  - Orbital myositis after delivery.

PMID- 18055102
TI  - Plasma glutamate and glycine levels in patients with amyotrophic lateral
      sclerosis: the effect of riluzole treatment.
AB  - OBJECTIVES: Defective glutamate (glu) metabolism and excitotoxicity have been
      implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Moreover,
      glycine (gly) has been shown to potentiate excitatory transmission. The
      "antiglutamatergic" agent riluzole has been shown to prolong survival in ALS. The
      aim of the study was to investigate a possible effect of riluzole on plasma glu
      and gly levels, correlating with clinical response to treatment. PATIENTS AND
      METHODS: Plasma concentrations of glu and gly were measured in 20 healthy
      volunteers and 22 ALS patients before treatment and after 6 months on riluzole.
      RESULTS: At baseline, increased plasma glu correlated with spinal onset and male
      gender whereas gly levels did not differ between patients and controls. No
      significant change was observed for both amino acids post-treatment, despite a
      lower rate of disease progression. CONCLUSION: These results suggest that
      riluzole may affect disease progression without a significant impact on plasma
      glu and gly levels, possibly indicating different mechanisms of drug action.

PMID- 18055103
TI  - Association between metabolic syndrome and previous ischemic lesions in patients
      with intracranial atherosclerotic stroke.
AB  - OBJECTIVES: To elucidate the relationship between MetS and ischemic stroke, we
      evaluated the association of MetS and individual components with frequency of
      ischemic stroke lesions and investigated the independent associations between
      them in acute ischemic stroke patients. PATIENTS AND METHODS: We evaluated 370
      acute ischemic stroke patients who underwent brain magnetic resonance (MR)
      imaging and MR angiography. The stroke subgroups were categorized as intracranial
      large artery atherosclerosis (IC-LAA, n=151), extracranial large artery
      atherosclerosis (EC-LAA, n=35), and nonatherosclerosis (NA, n=184). MetS was
      defined using the criteria of the International Diabetes Federation. RESULTS:
      Patients with IC-LAA group showed a higher rate of MetS and previous ischemic
      lesions (predominantly deep gray/white matter) than those with EC-LAA and NA (all
      P<0.001). The number of previous ischemic lesions showed a tendency to increase
      as the number of MetS components increased in the IC-LAA group (P=0.004). In the
      IC-LAA group, age (OR, 1.04) and MetS (OR, 3.28) were independently associated
      with previous ischemic lesions (all P<0.001), which was prominent with more
      severe MetS components after adjustment for risk factors (P<0.001). Among the
      component conditions, high blood pressure, impaired fasting glucose, and
      abdominal obesity were more associated with previous ischemic lesions (all
      P<0.001) than low high-density lipoprotein and high triglyceride levels (P=0.010
      and 0.028, respectively). CONCLUSION: Our study showed a strong association
      between MetS and previous ischemic lesions, more in patients with IC-LAA.

PMID- 18055104
TI  - A huge occipital osteoblastoma accompanied with aneurysmal bone cyst in the
      posterior cranial fossa.
AB  - Osteoblastoma is an infrequent benign tumor and skull involvement is extremely
      rare. The occipital bone is much less frequently involved. We report an unusual
      case of a huge occipital osteoblastoma with aneurysmal bone cyst in the posterior
      cranial fossa of a 20-year-old young man. MRI scan and CT three-dimensional
      reconstruction revealed that the tumor (approximately 8.5 cm x 6 cm x 5 cm)
      occupied nearly half volume of the posterior cranial fossa. The cerebellum, the
      forth ventricle and brain stem were compressed remarkably and hydrocephalus was
      noted. The tumor mass was multiloculated cystic and highly vascular. Excessive
      bleeding occurred during operation and total removal was achieved. The patient
      was symptom-free and MRI scan revealed no evidence of recrudescence after a
      follow-up period of 18 months. Pathological examination revealed that the lesion
      was a benign osteoblastoma with secondary aneurysmal bone cyst (ABC). ABC
      constitutes a highly vascular lesion while complete surgical resection is often
      impeded by excessive intraoperative bleeding. Preoperative embolization may
      reduce the risk. Despite the benign nature of osteoblastoma, local recurrence
      after incomplete resection is not rare and malignant transformation during
      recurrence may occur even after adequate surgery. Our case confirms the findings
      of previous investigators that if osteoblastoma is removed completely, no
      recurrence is expected even without adjuvant irradiation and chemotherapy.

PMID- 18055105
TI  - Methylphenidate and chromosome damage.

PMID- 18055106
TI  - The role of pH in nanofiltration of atrazine and dimethoate from aqueous
      solution.
AB  - This study examined the performance of nanofiltration membranes to retain
      atrazine and dimethoate in aqueous solution under different pH conditions. Four
      nanofiltration membranes, NF90, NF200, NF270 and DK are selected to be examined.
      The operating pressure, feed pesticide and stirring rate were kept constant at
      6x10(5) Pa, 10 mg/L and 1000 rpm. It was found that increasing the solution's pH
      increased atrazine and dimethoate rejection but reduced the permeate flux
      performance for NF200, NF270 and DK. However, NF90 showed somewhat consistent
      performance in both rejection and permeate flux regardless of the solution's pH.
      NF90 maintained above 90% of atrazine rejection and approximately 80% of
      dimethoate rejection regardless of the changes in solution's pH. Thus, NF90 is
      deemed the more suitable nanofiltration membrane for atrazine and dimethoate
      retention from aqueous solution compared to NF200, NF270 and DK.

PMID- 18055107
TI  - Rapid assessment of the latent hazard posed by dissolved mercaptans within
      aqueous effluent.
AB  - The presence of mercaptans (RSH) can usually be detected by their inherent
      noxious odour but there is a need to quantify the concentration within effluent
      and hence allow an assessment of the latent hazard to be made prior to disposal.
      The versatility of using naphthoquinone as a rapid derivatising agent through
      which to trap such species has been evaluated. The quinone moiety provides a
      label that can be quantified using colorimetric, electrochemical and
      chromatographic means and offers a significant advantage over conventional thiol
      labelling agents. The analytical characteristics of each approach have been
      investigated and the selectivity, sensitivity and applicability of the reaction
      system critically assessed for a range of model compounds. The naphthoquinone
      system has a detection limit in the low micromolar range with little interference
      from other components common to discharge water with 96% recovery of
      mercaptopropionate. The reaction to sulfide (HS-) has also been assessed and a
      disparity in response between the detection methods observed and a possible
      reaction pathway outlined.

PMID- 18055108
TI  - Extraction of heavy metal ions from leachate of cement-based stabilized waste
      using purpurin functionalized resin.
AB  - A new chelating resin was synthesized by functionalization of a polymer support,
      Amberlite XAD-2 with purpurin through an azo linkage (NN). The products were
      characterized by scanning electron microscopy, elemental analysis, Fourier
      transform infrared spectroscopy and thermogravimetric analysis. The optimum
      conditions for the extraction of Cd(II), Cr(III) and Pb(II) in two matrices;
      leachate from cement-based material and de-ionized water, were studied by batch
      and column methods. The determination of the metal ions was carried out by flame
      atomic absorption spectrometry. The optimum pH for the extraction of all metal
      ions in both matrices were at 4.0. Their sorption equilibrium was reached within
      1h. The sorbed Cd(II) and Pb(II) were eluted by 1% HNO3 within 10 min with the
      desorption recovery of >90%. The elution of Cr(III) by 3% H2O2 in 0.1 M NaOH was
      achieved within 30 min with the desorption recovery of >80%. The sorption
      capacity of Cd(II), Cr(III) and Pb(II) onto the resin was 75.0, 68.2, 82.7
      micromol g(-1) resin in DI water and 54.1, 46.5 and 55.7 micromol g(-1) resin in
      leachate, respectively. The extraction efficiency in the column method can be
      improved using the recirculation system. This new method gave a good accuracy in
      batch system with the recovery of 86.5 and 89.9% for Cd(II) and Pb(II) and R.S.D.
      less than 2.3% (n=14).

PMID- 18055109
TI  - Effect of Cu(II), Cd(II) and Zn(II) on Pb(II) biosorption by algae Gelidium
      derived materials.
AB  - Biosorption of Pb(II), Cu(II), Cd(II) and Zn(II) from binary metal solutions onto
      the algae Gelidium sesquipedale, an algal industrial waste and a waste-based
      composite material was investigated at pH 5.3, in a batch system. Binary
      Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II) solutions have been tested. For
      the same equilibrium concentrations of both metal ions (1 mmol l(-1)),
      approximately 66, 85 and 86% of the total uptake capacity of the biosorbents is
      taken by lead ions in the systems Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II),
      respectively. Two-metal results were fitted to a discrete and a continuous model,
      showing the inhibition of the primary metal biosorption by the co-cation. The
      model parameters suggest that Cd(II) and Zn(II) have the same decreasing effect
      on the Pb(II) uptake capacity. The uptake of Pb(II) was highly sensitive to the
      presence of Cu(II). From the discrete model it was possible to obtain the
      Langmuir affinity constant for Pb(II) biosorption. The presence of the co-cations
      decreases the apparent affinity of Pb(II). The experimental results were
      successfully fitted by the continuous model, at different pH values, for each
      biosorbent. The following sequence for the equilibrium affinity constants was
      found: Pb>Cu>Cd approximately Zn.

PMID- 18055110
TI  - Photocatalytic degradation of methyl red dye by silica nanoparticles.
AB  - Silica nanoparticles (SiO2 NPs) were found to be photocatalytically active for
      degradation of methyl red dye (MR). The SiO2 NPs and SiO2 NPs doped with silver
      (and or) gold nanoparticles were prepared. From the transmission electron
      microscopy (TEM) images the particle size and particle morphology of catalysts
      were monitored. Moreover, SiO2 NPs doped with silver and gold ions were used as a
      photocatalyst for degradation of MR. The rate of photocatalytic degradation of MR
      was found to be increased in the order of SiO2 NPs, SiO2 NPs coated with gold
      nanoparticles (Au NPs) and silver nanoparticles (Ag NPs), SiO2 NPs coated with Ag
      NPs, SiO2 NPs coated with Au NPs, Ag+-doped SiO2 NPs, and Au3+-doped SiO2 NPs.
      The kinetic and mechanism of photocatalytic reaction were studied and accorded
      well with experimental results.

PMID- 18055111
TI  - Equilibrium and kinetic data and process design for adsorption of Congo Red onto
      bentonite.
AB  - The adsorption of Congo Red onto bentonite in a batch adsorber has been studied.
      Four kinetic models, the pseudo first- and second-order equations, the Elovich
      equation and the intraparticle diffusion equation, were selected to follow the
      adsorption process. Kinetic parameters; rate constants, equilibrium adsorption
      capacities and correlation coefficients, for each kinetic equation were
      calculated and discussed. It was shown that the adsorption of Congo Red onto
      bentonite could be described by the pseudo second-order equation. The
      experimental isotherm data were analyzed using the Langmuir, Freundlich and
      Temkin equations. Adsorption of Congo Red onto bentonite followed the Langmuir
      isotherm. A single stage batch adsorber was designed for different adsorbent
      mass/treated effluent volume ratios using the Langmuir isotherm.

PMID- 18055112
TI  - Temporal recalibration to tactile-visual asynchronous stimuli.
AB  - Here we demonstrate that the perceptual system adapts to tactile-visual temporal
      asynchronies (i.e., temporal recalibration). Participants were exposed to a train
      of tactile and visual stimuli with a constant time lag (either -100ms, 0ms, or
      100ms; with negative values indicating that the tactile stimulus came first).
      Following exposure, they were presented tactile-visual test stimulus pairs and
      judged whether the tactile or the visual stimulus was presented first (Temporal
      Order Judgement). Results show that subjective simultaneity (the PSS) was shifted
      in the direction of the exposure lag. The results fit reports on auditory-visual
      temporal recalibration and indicate that the brain adapts to temporal
      incongruencies between modalities in general.

PMID- 18055113
TI  - SOD1A4V-mediated ALS: absence of a closely linked modifier gene and origination
      in Asia.
AB  - Familial amyotrophic lateral sclerosis (ALS) accounts for 10% of all ALS.
      Approximately 20% of cases are due to mutations in the Cu/Zn superoxide dismutase
      gene (SOD1). In North America, SOD1(A4V) is the most common SOD1 mutation.
      Carriers of the SOD1(A4V) mutation share a common phenotype with rapid disease
      progression and death on average occurring at 1.4 years (versus 3-5 years with
      other dominant SOD1 mutations). Previous studies of SOD1(A4V) carriers identified
      a common haplotype around the SOD1 locus, suggesting a common founder for most
      SOD1(A4V) patients. In the current study we sequenced the entire common
      haplotypic region around SOD1 to test the hypothesis that polymorphisms in either
      previously undescribed coding regions or non-coding regions around SOD1 are
      responsible for the more aggressive phenotype in SOD1(A4V)-mediated ALS. We
      narrowed the conserved region around the SOD1 gene in SOD1(A4V) ALS to 2.8Kb and
      identified five novel SNPs therein. None of these variants was specifically found
      in all SOD1(A4V) patients. It therefore appears likely that the aggressive nature
      of the SOD1(A4V) mutation is not a result of a modifying factor within the region
      around the SOD1 gene. Founder analysis estimates that the A4V mutation occurred
      540 generations (approximately 12,000 years) ago (95% CI 480-700). The conserved
      minimal haplotype is statistically more similar to Asian than European population
      DNA sets, suggesting that the A4V mutation arose in native Asian-Americans who
      reached the Americas through the Bering Strait.

PMID- 18055114
TI  - Local administration of a cannabinoid agonist alters norepinephrine efflux in the
      rat frontal cortex.
AB  - Delta(9)-tetrahydrocannabinol, the main psychoactive ingredient in marijuana,
      activates specific cannabinoid (CB) receptors to exert complex actions on
      modulatory neurotransmitters involved in attention and cognition. Previous
      research has demonstrated that systemic administration of the synthetic
      cannabinoid agonist, WIN 55,212-2, increases norepinephrine efflux in the frontal
      cortex. The distribution of CB1 receptors on noradrenergic fibers in the frontal
      cortex suggests this may be one potential site for the regulation of
      norepinephrine release. In the present study, we first examined the ability of a
      CB1 antagonist, applied locally in the frontal cortex of adult male Sprague
      Dawley rats, to block the actions of systemic WIN 55,212-2. Pretreatment with SR
      141716A (300 microM) significantly attenuated the excitatory effects of WIN
      55,212-2 (15 mg/kg, i.p.). Next, the impact of direct perfusion of WIN 55,212-2
      into the frontal cortex on extracellular norepinephrine efflux was measured.
      Direct application of WIN 55,212-2 (100 microM) into the frontal cortex elicited
      a significant increase in extracellular norepinephrine efflux suggesting that
      activation of cortical cannabinoid receptors contributes to alterations in
      norepinephrine levels in this brain region. Finally, local administration of SR
      141716A followed by local administration of WIN 55,212-2 revealed a paradoxical
      inhibition of norepinephrine efflux.

PMID- 18055115
TI  - Unilateral lesion of the subthalamic nucleus transiently provokes bilateral
      subacute glial cell proliferation in the adult rat substantia nigra.
AB  - Ablative or functional lesions of the subthalamic nucleus (STN) lead to
      significant improvements of motor deficits and major levodopa associated motor
      complications in patients with Parkinson's disease. The biological mechanisms
      underlying the clinical effectiveness still remain largely unknown. It has been
      demonstrated previously that the adult substantia nigra (SN) bears the capacity
      for cellular plasticity throughout adulthood and that this property can be
      influenced by external stimuli. In the present study we investigated the subacute
      and chronic effects of unilateral STN-lesion on newly generated neural cells in
      the adult healthy SN of the rat. With this experimental design we demonstrate a
      bilateral transient increase in the total numbers of newborn nigral cells
      following STN-lesion. Additionally, we show a transient bilateral decrease in the
      number of newborn neuro-glial antigen 2 (NG2)-positive and in the number of new
      microglia cells. No newborn neurons, however, were detected. Thus, we conclude
      that unilateral ablative STN lesion transiently changes plasticity of neural cell
      subpopulations in the healthy adult SN of the rat.

PMID- 18055116
TI  - Caspase-3 is related to infarct growth after human ischemic stroke.
AB  - Our aim was to investigate caspase-3 plasma levels after stroke, its correlation
      with infarct expansion and neurological outcome. Caspase-3 plasma levels were
      determined by ELISA at different time points after stroke in 116 t-PA-treated
      patients and a control group of 40 healthy controls. Neurological status was
      evaluated by NIHSS scores and functional outcome by modified Rankin Scale. To
      assess brain infarct growth, serial brain magnetic resonance imaging scans
      including diffusion- (DWI) and perfusion-weighted (PWI) images were performed in
      a subgroup of 58 patients. Plasma caspase-3 levels were higher in stroke patients
      versus the control group throughout the acute phase of stroke. Furthermore,
      caspase-3 level at 24h was associated with poorer short- and long-term
      neurological outcome and positively correlated with infarct growth assessed by
      diffusion-weighted images. Our data suggest that caspase-3 could be involved in
      recruitment of ischemic brain tissue being a marker of infarct growth.

PMID- 18055117
TI  - Treating chronic pain in the context of comorbid depression.

PMID- 18055118
TI  - Experimental transmission of Hepatozoon americanum to rodents.
AB  - Laboratory-raised cotton rats (Sigmodon hispidus), outbred white mice (Mus
      musculus), and C57BL/6J-Lystbg-J/J mice (M. musculus) that were administered
      approximately 50 sporulated oocysts of Hepatozoon americanum (AF176836) by gavage
      developed inflammatory lesions containing parasitic cystozoites in cardiac and
      skeletal muscle, kidney, and lung. Sprague-Dawley rats (Rattus norvegicus)
      similarly exposed showed no evidence of infection. Cystozoites were first
      detected by histopathologic examination four weeks after exposure to oocysts.
      Globular, PAS-positive material accumulated around the cystozoites as the
      duration of infection lengthened. Nested PCR analysis of tissues collected 16
      weeks post-exposure was positive for the 18S rRNA Hepatozoon sp. gene and the DNA
      sequence of the fragment amplified was 99.6% and 99.8% identical to H. americanum
      sequences previously reported from naturally-infected dogs (AF176836 and
      AY864676, respectively). Merogonous and gamontogonous stages of the parasite were
      not detected in any of the cystozoite-infected rodents.

PMID- 18055119
TI  - National study of the gastrointestinal parasites of dogs and cats in Australia.
AB  - The prevalence of gastrointestinal parasites in Australian pet dogs and cats was
      largely unknown prior to this study. Current recommendations for the prophylactic
      treatment of parasites in Australia are based on studies conducted 20-30 years
      ago. A total of 1400 canine and 1063 feline faecal samples were collected from
      veterinary clinics and refuges from across Australia. The overall prevalence of
      gastrointestinal parasites in dogs and cats was 23.9% (CI 21.7-26.1) and 18.4%
      (CI 16.1-20.7), respectively. Overall Giardia was the most prevalent parasite in
      dogs (9.3% CI 7.8-10.8) followed by hookworm (6.7% CI 5.4-8.0). Isospora felis
      was the most prevalent parasite in cats (5.6% CI 4.2-7.0), followed by Toxocara
      cati (3.2% CI 2.1-4.3). In conclusion the prevalence of intestinal helminths in
      Australian pet dogs and cats is low. Consequently, consideration should be given
      to the future use of anthelmintics and continued emphasis on pet owner education
      as means of preventing infection.

PMID- 18055120
TI  - Conventional and novel PET tracers for imaging in oncology in the era of
      molecular therapy.
AB  - In the last ten years, the development of several novel targeted drugs and the
      refinement of state of the art technologies such as the genomics and proteomics
      and their introduction to clinical practice have revolutionized the management of
      patients affected by cancer. However, everyday practice points out several
      clinical questions: the difficulty of response assessment to new drugs especially
      using standard RECIST criteria that do not provide information on biological,
      vascular or metabolic variations; the inadequate selection of patients who are
      likely to benefit from a targeted therapy excluding those with breast cancer and
      gastrointestinal stromal tumours; the need to know the global biological
      background of diseases especially in metastatic setting using repeatable non
      invasive procedures. Molecular imaging could provide information on in vivo
      distribution of biological markers in response to targeted therapy and could
      improve the selection of patients before therapies. The aim of this review is to
      analyze the current role of conventional and innovative positron emission
      tomography (PET) radiotracers in clinical practice and to explore the promising
      perspectives of molecular imaging in cancer research.

PMID- 18055121
TI  - Are opioid-sensitive neurons in the rostral ventromedial medulla inhibitory
      interneurons?
AB  - mu-Opioid agonists frequently activate output neurons in the brain via
      disinhibition, that is, by inhibiting "secondary cells," which results in
      disinhibition of "primary cells," considered to be output neurons. Secondary
      cells are generally presumed to be inhibitory interneurons that serve only to
      regulate the activity of the output neurons. However, studies of the opioid
      sensitive neurons in the rostral ventromedial medulla, a region with a well
      documented role in nociceptive modulation, indicate that the opioid-inhibited
      neurons in this region (termed "on-cells" when recorded in vivo) have a distinct
      functional role that parallels and opposes the output of the subset of RVM
      neurons that are activated following opioid administration, the "off-cells." The
      aim of the present study was to analyze the relative timing of on- and off-cell
      reflex-related firing in the rostral ventromedial medulla to help determine
      whether on-cells are likely to function as inhibitory interneurons in this
      region. On- and off-cells display complementary firing patterns during noxious
      evoked withdrawal: off-cells stop firing and on-cells show a burst of activity.
      If on-cells are inhibitory interneurons mediating the off-cell pause, the on
      cells would be expected to begin their reflex-related discharge before the off
      cells cease firing. To examine this we recorded activity of on- and off-cell
      pairs during heat-evoked paw or tail withdrawal in lightly anesthetized rats. For
      each cell pair, we measured the onsets of the off-cell pause and the on-cell
      burst. Contrary to what would be expected if on-cells were inhibitory
      interneurons, off-cells typically ceased firing before on-cells began reflex
      related firing, with a mean 481 (+/-69) ms lag between the final off-cell spike
      and the first on-cell spike. This suggests that on-cells do not mediate the off
      cell pause, and points instead to presynaptic mechanisms in opioid-mediated
      disinhibition of medullary output neurons. These data also support an independent
      role for on-cells in pain modulation.

PMID- 18055123
TI  - The reinstatement of amphetamine-induced place preference is long-lasting and
      related to decreased expression of AMPA receptors in the nucleus accumbens.
AB  - A great deal of effort has been devoted to elucidating the psychopharmacology
      underlying addiction and relapse. Long-term neuroadaptations in glutamate
      transmission seem to be of great relevance for relapse to stimulant abuse. In
      this study, we investigated amphetamine-induced conditioned place preference
      during adolescence and the reinstatement of the conditioned behavior following a
      priming injection of the drug 1 day (adolescence), 30 days (early adulthood) and
      60 days (adulthood) after the extinction test. The nucleus accumbens was
      dissected immediately after the reinstatement test to examine alterations in
      GluR1 and NR1 subunits of glutamatergic receptors. Our results showed that a
      priming injection of amphetamine was able to reinstate the CPP 1 and 30 days
      after extinction. However, it failed to reinstate the conditioned response after
      60 days. GluR1 levels were decreased on days 1 and 30 but not on day 60 while NR1
      levels were unaltered in the reinstatement test. Using a relapse model we found
      that reinstatement of amphetamine-induced conditioning place preference during
      adolescence is long lasting and persists through early adulthood. Decreased
      levels of GluR1 in the nucleus accumbens might be related to the reinstatement of
      amphetamine-induced conditioning place preference.

PMID- 18055122
TI  - Impaired nerve regeneration and enhanced neuroinflammatory response in mice
      lacking pituitary adenylyl cyclase activating peptide.
AB  - Peripheral nerve injury models are used to investigate processes that can
      potentially be exploited in CNS injury. A consistent change that occurs in
      injured peripheral neurons is an induction in expression of pituitary adenylyl
      cyclase activating peptide (PACAP), a neuropeptide with putative neuroprotective
      and neuritogenic actions. PACAP-deficient mice were used here to investigate
      actions of endogenous PACAP after facial nerve injury. Although motor neuron
      survival after axotomy was not significantly different in PACAP deficient vs.
      wild type mice, recovery of axon regeneration after crush injury was
      significantly delayed. The impaired regeneration was associated with 8- to 12
      fold increases in gene expression of proinflammatory cytokines tumor necrosis
      factor-alpha, interferon-gamma, interleukin (IL) -6, and a 90% decrease in the
      anti-inflammatory cytokine IL-4 at the injury site. Similar cytokine changes and
      an increased microglial response were observed in the brainstem facial motor
      nucleus. Because immunocompromised animals such as SCID mice are known to exhibit
      peripheral nerve regeneration defects, the observations raise the novel
      hypothesis that PACAP is critically involved in a carefully controlled immune
      response that is necessary for proper nerve regeneration after injury.

PMID- 18055124
TI  - Calcium influx through N-methyl-D-aspartate receptors triggers GABA release at
      interneuron-Purkinje cell synapse in rat cerebellum.
AB  - Ca(2+)-dependent neurotransmitter release was originally thought to occur only
      following activation of presynaptic voltage-gated calcium channels after a
      presynaptic action potential. Recent evidence suggests that not only opening of
      voltage-gated but also ligand-gated ion channels, such as neurotransmitter
      receptors, can trigger exocytosis, as well as Ca(2+) release from intracellular
      Ca(2+) stores. It was shown that activation of N-methyl-d-aspartate (NMDA)
      receptors on presynaptic interneurons led to increases in GABA release from these
      neurons onto postsynaptic Purkinje cells in rat cerebellum in the presence of
      tetrodotoxin (TTX), suggesting a presynaptic location for the underlying NMDA
      receptors. However, the mechanism for the NMDA-induced increase in GABA release
      remained unclear. The present study addresses the question whether Ca(2+) influx
      through presynaptic NMDA receptors alone is sufficient to trigger presynaptic
      GABA release at this synapse or whether activation of presynaptic NMDA receptors
      leads to opening of voltage-gated Ca(2+) channels, thereby increasing exocytosis.
      The results suggest that the NMDA-induced increase in presynaptic GABA release
      neither requires activation of presynaptic voltage-gated Ca(2+) channels nor
      Ca(2+) release from presynaptic Ca(2+) stores. It is concluded that Ca(2+) influx
      through the NMDA receptor alone is sufficient to drive presynaptic GABA release
      at the rat interneuron-Purkinje cell synapse.

PMID- 18055125
TI  - Electrophysiological characteristics of vasomotor preganglionic neurons and
      related neurons in the thoracic spinal cord of the rat: an intracellular study in
      vivo.
AB  - Sympathetic preganglionic neurons (SPN) represent the final central neurons in
      the sympathetic pathways which regulate vasomotor tone; they therefore play a
      pivotal role in the re-distribution of cardiac output to different vascular beds
      in response to environmental challenges. While the consensus view is that
      activity in these neurons is due mainly to supraspinal inputs, the possibility
      that some activity may be generated intrinsically and modified by synaptic inputs
      cannot be excluded. Therefore, in order to distinguish between these two
      possibilities, the electrophysiological properties of cardiovascular-like SPN in
      the upper thoracic spinal cord of the anesthetized rat were examined and their
      response to activation of vasodepressor inputs was investigated. Intracellular
      recordings were made from 22 antidromically identified SPN of which 17 displayed
      irregular, but maintained, spontaneous activity; no evidence of bursting behavior
      or pacemaker-like activity was observed. Stimulation of the aortic depressor
      nerve or a vasodepressor site within the nucleus tractus solitarius (NTS)
      resulted in a membrane hyperpolarization, decrease in cell input resistance and
      long-lasting cessation of neuronal firing in SPN including a sub-population which
      had cardiac-modulated patterns of activity patterns. Recordings were also
      undertaken from 80 non-antidromically-activated neurons located in the vicinity
      of SPN; 23% of which fired in phase with the cardiac cycle, with this peak of
      activity occurring before similar increases in cardiac-modulated SPN. Stimulation
      of vasodepressor regions of the NTS evoked a membrane hyperpolarization and
      decrease in cell input resistance in cardiac-modulated but not non-modulated
      interneurons. These studies show that activity patterns in SPN in vivo are
      determined principally by synaptic inputs. They also demonstrate that spinal
      interneurons which exhibit cardiac-modulated patterns of activity are
      postsynaptically inhibited following activation of baroreceptor pathways.
      However, the question as to whether these inhibitory pathways and/or
      disfacilitation of tonic excitatory drive underlies the baroreceptor-mediated
      inhibition of SPN remains to be determined.

PMID- 18055126
TI  - Aggrecan-based extracellular matrix is an integral part of the human basal
      ganglia circuit.
AB  - The extracellular matrix is known to be involved in neuronal communication and
      the regulation of plastic changes, and also considered to protect neurons and
      synapses against damage. The goal of this study was to investigate how major
      extracellular matrix components (aggrecan, link protein, hyaluronan) constitute
      the pathways of the nigral system in the human basal ganglia circuit affected by
      neurodegeneration in Parkinson's disease. Here we show that aggrecan- and link
      protein-related components form clear regional distribution patterns, whereas
      hyaluronan is widely distributed in gray and white matter. Two predominant
      phenotypes of the aggrecan-based matrix can be discriminated: (1) perineuronal
      nets (PNs) and (2) axonal coats (ACs) encapsulating preterminal fibers and
      synaptic boutons. Clearly contoured PNs are associated with GABAergic projection
      neurons in the external and internal division of the globus pallidus, the lateral
      and reticular part of the substantia nigra, as well as subpopulations of striatal
      and thalamic inhibitory interneurons. Dopaminergic nigral neurons are devoid of
      PNs but are contacted to a different extent by matrix-coated boutons forming
      subnucleus-specific patterns. A very dense network of ACs is characteristic
      especially of the posterior lateral cell groups of the compact substantia nigra
      (nigrosome 1). In the subthalamic nucleus and the lateral thalamic nuclei
      numerous AC-associated axons were attached to principal neurons devoid of PNs. We
      conclude from the region-specific patterns that the aggrecan-based extracellular
      matrix is adapted to the fast processing of sensorimotor activities which are the
      therapeutic target of surgery and deep brain stimulation in the treatment of
      advanced stages of Parkinson's disease.

PMID- 18055127
TI  - Administration of the protein synthesis inhibitor, anisomycin, has distinct sleep
      promoting effects in lateral preoptic and perifornical hypothalamic sites in
      rats.
AB  - Although a robust relationship between sleep and increased brain protein
      synthesis is well-documented, there have been few reports of the effects of local
      application of a protein synthesis inhibitor (PSI) on sleep. In this study, we
      compared the effects of local microdialytic administration of the protein
      synthesis inhibitor, anisomycin (ANI) into the lateral preoptic area (LPOA), a
      sleep promoting area vs. the perifornical/lateral hypothalamus (PF/LH), a wake
      and rapid eye movement (REM) sleep-promoting area. ANI administered to the LPOA
      at night resulted in an increase in stage 2 of rat non-REM sleep, whereas ANI
      delivered into the PF/LH during the daytime increased REM sleep. ANI
      microdialysis into hippocampus did not affect sleep or waking. These differential
      effects of local protein synthesis inhibition on sleep support a hypothesis that
      mechanisms controlling protein synthesis are critically involved in the
      regulation of both NREM sleep and REM sleep.

PMID- 18055128
TI  - Characterization of some morphological parameters of orbicularis oculi motor
      neurons in the monkey.
AB  - The primate facial nucleus is a prominent brainstem structure that is composed of
      cell bodies giving rise to axons forming the facial nerve. It is musculotopically
      organized, but we know little about the morphological features of its motor
      neurons. Using the Lucifer Yellow intracellular filling method, we examined 11
      morphological parameters of motor neurons innervating the monkey orbicularis
      oculi (OO) muscle, which plays an important role in eyelid closure and voluntary
      and emotional facial expressions. All somata were multipolar and remained
      confined to the intermediate subnucleus, as did the majority of its aspiny
      dendritic branches. We found a mean maximal cell diameter of 54 microm in the
      transverse dimension, cell diameter of 60 microm in the rostrocaudal dimension,
      somal surface area of 17,500 microm(2) and somal volume of 55,643 microm(3).
      Eight neurons were used in the analysis of dendritic parameters based upon
      complete filling of the distal segments of the dendritic tree. We found a mean
      number of 16 dendritic segments, an average dendritic length of 1036 microm,
      diameter of 7 microm, surface area of 12,757 microm(2) and total volume of 16,923
      microm(3). Quantitative analysis of the dendritic branch segments demonstrated
      that the average number, diameter and volume gradually diminished from proximal
      to distal segments. A Sholl analysis revealed that the highest number of
      dendritic intersections occurred 60 microm distal to the somal center with a
      gradual reduction of intersections occurring distally. These observations advance
      our understanding of the morphological organization of the primate facial nucleus
      and provide structural features for comparative studies, interpreting afferent
      influence on OO function and for designing studies pinpointing structural
      alterations in OO motor neurons that may accompany disorders affecting facial
      movement.

PMID- 18055129
TI  - Brain-derived neurotrophic factor activation of extracellular signal-regulated
      kinase is autonomous from the dominant extrasynaptic NMDA receptor extracellular
      signal-regulated kinase shutoff pathway.
AB  - NMDA receptors bidirectionally modulate extracellular signal-regulated kinase
      (ERK) through the coupling of synaptic NMDA receptors to an ERK activation
      pathway that is opposed by a dominant ERK shutoff pathway thought to be coupled
      to extrasynaptic NMDA receptors. In the present study, synaptic NMDA receptor
      activation of ERK in rat cortical cultures was partially inhibited by the highly
      selective NR2B antagonist Ro25-6981 (Ro) and the less selective NR2A antagonist
      NVP-AAM077 (NVP). When Ro and NVP were added together, inhibition appeared
      additive and equal to that observed with the NMDA open-channel blocker MK-801.
      Consistent with a selective coupling of extrasynaptic NMDA receptors to the
      dominant ERK shutoff pathway, pre-block of synaptic NMDA receptors with MK-801
      did not alter the inhibitory effect of bath-applied NMDA on ERK activity. Lastly,
      in contrast to a complete block of synaptic NMDA receptor activation of ERK by
      extrasynaptic NMDA receptors, activation of extrasynaptic NMDA receptors had no
      effect upon ERK activation by brain-derived neurotrophic factor. These results
      suggest that the synaptic NMDA receptor ERK activation pathway is coupled to both
      NR2A and NR2B containing receptors, and that the extrasynaptic NMDA receptor ERK
      inhibitory pathway is not a non-selective global ERK shutoff.

PMID- 18055130
TI  - An application of the Theory of Planned Behavior to sorority alcohol consumption.
AB  - Greek-affiliated college students have been found to drink more heavily and
      frequently than other students. With female student drinking on the rise over the
      past decade, sorority women may be at particular risk for heavy consumption
      patterns. The current study is the first to apply the Theory of Planned Behavior
      (TPB) to examine drinking patterns among a sorority-only sample. Two-hundred and
      forty-seven sorority members completed questionnaires measuring TPB variables of
      attitudes, norms, perceived behavioral control, and intentions, with drinking
      behaviors measured one month later. Latent structural equation modeling examined
      the pathways of the TPB model. Intentions to drink mediated the relationship
      between attitudes and norms on drinking behavior. Subjective norms predicted
      intentions to drink more than attitudes or perceived behavioral control.
      Perceived behavioral control did not predict intentions but did predict drinking
      behaviors. Interpretation and suggestions from these findings are discussed.

PMID- 18055131
TI  - Tobacco and hazardous or harmful alcohol use in Thailand: joint prevalence and
      associations with socioeconomic factors.
AB  - This study estimates the individual and joint prevalence of cigarette smoking and
      alcohol misuse, and examines the association between these risks and
      socioeconomic factors in Thailand. The self-reported data on cigarette and
      alcohol use are from a 2004 nationally representative cross-sectional survey of
      39290 individuals aged 15 and over. Substantially more men than women were
      current smokers (45.8% vs. 2.3%; p<0.001) as well as harmful (5.4% vs. 0.9%,
      p<0.0001) and hazardous alcohol users (11.2% vs. 1.2%, p<0.001). The strongest
      predictor of alcohol misuse was smoking, and the strongest predictor of smoking
      was alcohol misuse in both sexes. There was an inverse relationship between
      education and family income with the odds of current smoking, whereas average
      levels of family income (not low or high) were associated with higher odds of
      harmful or hazardous alcohol use. Tobacco and alcohol misuse could be more
      effectively addressed by targeting and tailoring programs towards those who are
      most at risk - joint tobacco and harmful or hazardous alcohol users, and those of
      lower socioeconomic status.

PMID- 18055132
TI  - Hibernating mammals in sudden cardiac death in epilepsy: what do they tell us?
AB  - Epilepsy is the most common neurological disorder; approximately 1% of the
      population worldwide have epilepsy. Moreover, sudden unexpected death in epilepsy
      (SUDEP) is the most important direct epilepsy-related cause of death. Information
      concerning risk factors for SUDEP is conflicting, but potential risk factors
      include: age, early onset of epilepsy, duration of epilepsy, uncontrolled
      seizures, seizure frequency and AED number. Additionally, the cause of SUDEP is
      still unknown; however, the most commonly suggested mechanisms are cardiac
      abnormalities during and between seizures. Very recently, our research group was
      the first to annunciate that winter temperatures may lead a cardiac abnormalities
      and hence sudden death, become a new potential risk factor to SUDEP. Quite
      interesting, several mammalian species have evolved to develop a physiological
      phenomenon called hibernation as a strategy for survival under adverse cold
      conditions. From cardiovascular point of view, it has been established that
      hibernating mammals inherited a stable cardiovascular function as a result of
      adaptation to extreme external and internal environments during hibernation. For
      instance, hibernating mammals show resistance to hypothermia at a cellular level,
      the membrane potentials and excitability are more stable in the cardiac cells of
      these animals (action potentials (60 mV) have been recorded in hibernators
      myocardium at -5 degrees C), the aortic smooth muscle cells from hibernators are
      able to maintain ionic gradients upon prolonged exposure to low temperatures, and
      cardiac myocytes from hibernating mammals maintain constant levels of
      intracellular free calcium and forceful contractility at 10 degrees C or lower.
      Taken together, in this paper we postulate that hibernators have some
      cardiovascular particularities that confer heart protection that could positively
      influence the cardiovascular system of patients with epilepsy.

PMID- 18055133
TI  - Alpha synuclein protein levels are increased in serum from recently abstinent
      cocaine abusers.
AB  - Alpha synuclein is increased in dopamine neurons of cocaine abusers and in rats
      whose alcohol preference is inbred. Recent studies have shown increased alpha
      synuclein protein expression in serum of alcoholic patients that is linked with
      severity of alcohol craving. The aim of this study was to analyze the serum
      levels of alpha synuclein in healthy subjects and in recently abstinent cocaine
      abusers. Alpha synuclein protein expression was measured by enzyme-linked
      immunosorbent assay in serum specimens obtained from 38 recently abstinent
      cocaine dependent patients and 14 control subjects. The presence of cocaine
      dependence disorder was based on the Structured Clinical Interview (DSM-IV). Drug
      severity was assessed by the Addiction Severity Index ratings and composite
      measures. Scores of the intensity and frequency of cocaine craving episodes were
      obtained from the Minnesota Cocaine Craving Questionnaire. The serum
      concentrations of alpha synuclein in cocaine dependent patients were
      significantly higher as compared with age-matched drug-free controls (p<0.001).
      Alpha synuclein levels in blood were significantly correlated with the intensity
      (r=0.60, p<0.001) and frequency (r=0.64, p<0.001) of cocaine craving and with 30
      days of cocaine use in the prior month before entry to treatment (r=0.56,
      p<0.005). However, there was no correlation between the serum protein levels of
      alpha synuclein and age in either group. This report is the first demonstration
      of altered alpha synuclein levels in peripheral blood from cocaine abusers. These
      data agree with previous reports in postmortem brain of cocaine abusers and
      provide support for an association between alpha synuclein and cocaine
      dependence.

PMID- 18055134
TI  - Changes in smoking behaviours from late childhood to adolescence: 4 years later.
AB  - The purpose of this short report is to estimate trajectories documenting changes
      in the frequency of cigarette smoking between 10-11 and 20-21 years of age for
      3959 participants to the Canadian National Longitudinal Survey of Children and
      Youth. This study is a follow up to Maggi, Hertzman, and Vaillancourt [Maggi, S.,
      Hertzman, C., Vaillancourt, T., 2007. Changes in smoking behaviours from late
      childhood to adolescence: insights from the Canadian National Longitudinal Survey
      of Children and Youth. Health Psychol. 26, 232-240] who found that there are five
      distinct trajectories of acquisition of smoking from 10-11 to 16-17 years of age.
      While findings from this study replicate those reported in Maggi, Hertzman, and
      Vaillancourt [Maggi, S., Hertzman, C., Vaillancourt, T., 2007. Changes in smoking
      behaviours from late childhood to adolescence: insights from the Canadian
      National Longitudinal Survey of Children and Youth. Health Psychol. 26, 232-240],
      they provide a more accurate representation of the possible outcomes of the
      smoking acquisition process by indicating what specific trajectories of
      experimentation may lead to daily smoking, occasional smoking or non-smoking.

PMID- 18055135
TI  - Deciphering the cis-regulatory elements of co-expressed genes in PCOS by in
      silico analysis.
AB  - In recent times, the focus of research in polycystic ovary syndrome (PCOS) has
      shifted from candidate gene(s) approach to whole genome analysis for deciphering
      its molecular pathophysiology. In this regard, several microarray studies have
      been published, showing differential expression of genes between normal and PCOS
      states. Co-expression of genes as obtained in microarray experiments can also
      imply co-regulation at the transcriptional level by various transcription
      factors. In order to identify such transcription factors, the in silico
      elucidation of Transcription Factor Binding Sites (TFBS) is emerging as an
      important tool. With this hypothesis, we looked for TFBS over-representation in a
      PCOS microarray gene set (n=130) using in silico tools. We extracted 1000 bps
      upstream and 200 bps downstream regions from all these genes and identified 4
      different TFBS, which were over-represented as compared to a human promoter
      background model. These four transcription factors are Staf, E47, CCAAT and CRE
      BP1/c-jun. The role of these transcription factors and their compatible members
      in PCOS pathophysiology is described in details in the text. The factors might
      provide a novel insight into the pathophysiology of PCOS.

PMID- 18055136
TI  - Fleece rot and dermatophilosis in sheep.
AB  - Fleece rot and dermatophilosis reduce health and production of sheep and
      predispose them to blow fly strike. This paper reviews aetiology, prevalence,
      pathogenesis, resistance, attempts to develop vaccines and prospects for new
      control strategies to these important skin diseases. Although the severity of
      fleece rot is associated with the abundance of Pseudomonas aeruginosa on skin,
      microbial ecology studies are providing new insights into the contribution of
      other bacteria to the disease. Wool traits and body conformation traits that
      predispose sheep to fleece rot and dermatophilosis are heritable and have been
      used as indirect selection criteria for resistance for many years. Selection
      against BoLA-DRB3-DQB class II haplotype in cattle can substantially reduce the
      prevalence of dermatophilosis and holds promise for identification of gene
      markers for resistance to these bacterial diseases in sheep. Immune responses in
      skin and systemic antibody responses to bacterial antigens are acquired through
      natural infection and contribute to resistance; however, prototype antibacterial
      vaccines have to date failed to provide protection against the diversity of
      isolates of Dermatophilus congolensis and Pseudomonas species present in the
      field. Opportunities for future control through breeding for resistance, vaccines
      and non-vaccine strategies for controlling the microbial ecology of fleece are
      discussed. In combination, control strategies need to reduce the risk of
      transmission, minimise exposure of animals to stressors that enhance the risk of
      infection, and enhance resistance though genetics or vaccines.

PMID- 18055137
TI  - Familial associations with paratuberculosis ELISA results in Texas Longhorn
      cattle.
AB  - The objective of this cross-sectional study was to estimate familial associations
      with paratuberculosis ELISA status in beef cattle. Texas Longhorn cattle (n=715)
      greater than 2years of age were sampled for paratuberculosis testing using ELISA
      and fecal culture. Diagnostic test results were indicative of substantial numbers
      of false-positive serological reactions consistent with environmental exposure to
      non-MAP Mycobacterium spp. Associations between ancestors and paratuberculosis
      ELISA status of offspring were assessed using conditional logistic regression.
      The association between ELISA status of the dam and her offspring was assessed
      using linear mixed-effect models. Significant associations were identified
      between some ancestors and offspring ELISA status. The odds of being classified
      as "suspect" or greater based on ELISA results were 4.6 times greater for
      offspring of dams with similarly increased S:P ratios. A significant positive
      linear association was also observed between dam and offspring log-transformed
      S:P ratios. Results indicate that there is familial aggregation of
      paratuberculosis ELISA results in beef cattle and suggest that genetic selection
      based on paratuberculosis ELISA status may decrease seroprevalence. However,
      genetic selection may have minimal effect on paratuberculosis control in herds
      with exposure to non-MAP Mycobacterium spp.

PMID- 18055139
TI  - Follicular and steroid hormone changes in Arabian mares in the postpartum period.
AB  - In this study, the aim has been to characterize the profiles of progesterone,
      estradiol and follicular changes during postpartum period from parturition to
      first postpartum ovulation. Jugular venous blood was taken daily for progesterone
      and estradiol assay until first postpartum ovulation. The diameters of the
      follicles of the ovaries were recorded. The mean progesterone and estrogen
      concentrations markedly decreased (p<0.05) during the 48h after parturition. No
      correlation was observed between estradiol concentrations and the diameter of the
      largest follicle whereas a negative correlation was present between the number of
      follicles smaller than 20mm and the number of follicles larger than 20mm on the
      third and fourth days after postpartum.

PMID- 18055138
TI  - High inter-species and low intra-species variation in 16S-23S rDNA spacer
      sequences of pathogenic avian mycoplasmas offers potential use as a diagnostic
      tool.
AB  - In order to investigate its value for phylogenetic analysis, species
      characterisation and diagnosis, the 16S-23S rDNA intergenic spacer regions (ISRs)
      of the type strain of 23 avian Mycoplasma species were amplified and the
      sequences determined. Also sequenced were the reference strains of Mycoplasma
      iowae serotypes J, K, N, Q and R and a number of field strains of Mycoplasma
      synoviae, Mycoplasma gallisepticum, Mycoplasma meleagridis and M. iowae. The ISRs
      demonstrated a high level of size variation (178-2488bp) between species and did
      not include tRNA genes. Phylogenetic analysis performed using the information
      conflicted with that based on the 16S rDNA and was therefore not helpful for
      phylogenetic studies. However, the ISR did appear to be of value for determining
      species since there was high inter-species variation between all 23 avian
      Mycoplasma species, and in addition there was low intra-species variation, at
      least in the four pathogenic species. It could also be very useful as additional
      information in the description of a new species and as a target for species
      specific PCRs.

PMID- 18055140
TI  - PLGA-based drug delivery systems: importance of the type of drug and device
      geometry.
AB  - Different types of ibuprofen- and lidocaine-loaded, poly(lactic-co-glycolic acid)
      (PLGA)-based microparticles and thin, free films of various dimensions were
      prepared and physico-chemically characterized in vitro. The obtained experimental
      results were analyzed using mathematical theories based on Fick's second law of
      diffusion. Importantly, the initial drug loadings were low in all cases (4%,
      w/w), simplifying the mathematical treatment and minimizing potential effects of
      the acidic/basic nature of the two model drugs on polymer degradation.
      Interestingly, the type of drug and device geometry strongly affected the
      resulting release kinetics and relative importance of the involved mass transport
      mechanisms. For instance, the relative release rate was almost unaffected by the
      system size in the case of spherical microparticles, but strongly depended on the
      thickness of thin, free films, irrespective of the type of drug. Ibuprofen and
      lidocaine release was found to be primarily diffusion controlled from the
      investigated PLGA-based microparticles for all system sizes, whereas diffusion
      was only dominant in the case of the thinnest free films. Interestingly, the type
      of drug did not significantly affect the resulting polymer degradation kinetics.
      However, ibuprofen release was always much faster than lidocaine release for all
      system geometries and sizes. This can probably be attributed to attractive ionic
      interactions between protonated, positively charged lidocaine ions and negatively
      charged, deprotonated carboxylic end groups of PLGA, hindering drug diffusion.
      The determined apparent diffusion coefficients of the drugs clearly point out
      that the mobility of an active agent in PLGA-based delivery systems does not only
      depend on its own physico-chemical properties and the type of PLGA used, but also
      to a large extent on the size and shape of the device. This has to be carefully
      taken into account when developing/optimizing this type of advanced drug delivery
      systems.

PMID- 18055141
TI  - Methacholine dry powder inhaler as a new tool for bronchial challenge test.
AB  - BACKGROUND: The methacholine (MCH) challenge test is performed to detect
      bronchial hyperresponsiveness in subjects suffering from asthma. It is conducted
      by inhaling spasmogen substances at increasing doses and measuring FEV1-PD20
      variation following the bronchoconstriction evoked. AIM: This paper describes a
      new method for MCH challenge test using pre-metered respirable powders of MCH at
      different doses for facilitating test execution. The availability of a series of
      pre-metered doses gives higher control over aerosolized dose and fine particle
      fraction (respirable dose), improving the accuracy and repeatability of the test.
      Dosimetric tests with MCH solution and pre-dosed powder challenge tests were
      clinically compared. METHODS AND MATERIALS: The inhalation powders were prepared
      by spray drying of solutions of methacholine, mannitol and
      hydroxypropylmethylcellulose in which different concentrations of MCH were
      included. The methacholine powders prepared were carefully characterized in terms
      of aerodynamic properties. RESULTS: Inhalation powders containing methacholine
      from 12.5 to 200 microg per metered dose, having a fine particle fraction between
      40 and 60%, were prepared using mannitol and cellulose polymer. Eighteen subjects
      (12 hyperresponsive and six normal) were subjected to both the MCH solution and
      powder tests in random sequence. No significant differences in FEV1 and PD20
      values were found between the challenge tests performed with liquid and powder
      formulations of methacholine. CONCLUSIONS: Powders of MCH having high
      respirability of the delivered doses can be prepared by spray drying. They allow
      for the performance of a challenge test using a dry powder inhaler. The powder
      dose series can be an alternative to the current dosimetric test with MCH
      solutions.

PMID- 18055143
TI  - Frog intestinal sac as an in vitro method for the assessment of intestinal
      permeability in humans: Application to carrier transported drugs.
AB  - The aim of this study was to investigate the presence of pharmaceutically
      relevant drug transporters in frog intestine which has been proposed as model for
      intestinal permeability screening assays of passively absorbed drugs in humans
      [Trapani, G., Franco, M., Trapani, A., Lopedota, A., Latrofa, A., Gallucci, E.,
      Micelli, S., Liso, G., 2004. Frog intestinal sac: a new in vitro method for the
      assessment of intestinal permeability. J. Pharm. Sci. 93, 2909-2919]. The
      expression of transporters in frog intestine was supported by the following
      observations: (i) the involvement of purine nucleobase transport system was
      deduced by inhibition of acyclovir transport in the presence of adenine; (ii)
      baclofen or l-dopa transport was inhibited by the digitalis steroid ouabain and
      it may be related to the Na(+) electrochemical potential difference, presumably
      involving amino acid transporters; (iii) the presence of proton-dependent peptide
      transporters was argued evaluating the effect of the pH change (from pH 5.9 to pH
      7.4) on the transport of glutathione; (iv) the possible expression in the frog
      intestine of an efflux system distinct from P-glycoprotein (Pgp) in the
      benzylpenicillin transport was deduced using a glucose enriched frog Ringer with
      or without the known Pgp inhibitor verapamil; (v) the contribution of Pgp
      mediated efflux system in determining the frog intestinal absorption of drugs was
      supported by the specific inhibition of cimetidine or nadolol transport in the
      presence of verapamil. These results indicate that pharmaceutically relevant drug
      transporters should be also expressed in frog intestine. In this work, an attempt
      was also made to compare the measured P(app) values in the frog intestinal model
      for the aforementioned series of actively/effluxed transported drugs in humans to
      the corresponding literature values for the fraction absorbed. The P(app) values
      used in these comparisons were obtained at high concentrations of drugs at which
      probably saturation of the carrier occurs. Interestingly, it was found that drugs
      that are completely absorbed had P(app) values >3 x 10(-6)cm/s, while drugs
      absorbed <90% had P(app) values lower than 1 x 10(-6)cm/s. In these cases,
      indeed, a borderline region characterized by the apparent permeability
      coefficient P(app) value between 1 x 10(-6) and 3 x 10(-6)cm/s should be
      considered for which the prediction of the absorbed fraction after oral
      administration in humans become more uncertain by the frog intestinal sac system.

PMID- 18055142
TI  - A novel system for three-pulse drug release based on "tablets in capsule" device.
AB  - The objective of the present study was to obtain programmed drug delivery from a
      novel system, which contains a water-soluble cap, impermeable capsule body, and
      two multi-layered tablets. Types of materials for the modulating barrier and its
      weight can significantly affect the lag time (defined as the time when drug
      released 8% of the single pulse dosage). We chose sodium alginate and hydroxy
      propyl methyl cellulose (HPMC E5) as the candidate modulating barrier material.
      Through adjusting ratio of sodium alginate and lactose, lag time was controllable
      between the first two pulsatile release. Linear relationship was observed between
      the ratio and the lag time. Through adjusting the ratio of HPMC E5/lactose, lag
      time between the second and the third pulse can be successfully modulated. In
      further studies, drug release rate of the second pulsatile dose can be improved
      by adding a separating layer between the third and the modulating barrier layer
      in the three-layered tablet. To evaluate contribution of bulking agent to drug
      release rate, lactose, sodium chloride, and effervescent blend were investigated.
      No superiority was found using sodium chloride and effervescent blend. However,
      lactose favored it. The results reveal that programmed drug delivery to achieve
      pulsatile drug release for three times daily can be obtained from these tablets
      in capsule system by systemic formulation approach.

PMID- 18055144
TI  - Psyllium and copolymers of 2-hydroxylethylmethacrylate and acrylamide-based novel
      devices for the use in colon specific antibiotic drug delivery.
AB  - In order to utilize the psyllium husk, a medicinally important natural
      polysaccharide, to develop the hydrogels meant for the drug delivery, we have
      prepared psyllium 2-hydroxylethylmethacrylate (HEMA) and acrylamide (AAm)-based
      polymeric networks by using N,N'-methylenebisacrylamide (N,N'-MBAAm) as
      crosslinker and ammonium persulfate (APS) as initiator. The polymeric networks
      thus formed [psy-cl-poly(HEMA-co-AAm)] were characterized with FTIR and swelling
      studies which were carried out as a function of crosslinker concentration, time,
      pH and [NaCl] of the swelling medium. The swelling kinetics of the hydrogels and
      in vitro release dynamics of model drug (tetracycline hydrochloride) from these
      hydrogels has been studied for the evaluation of swelling mechanism and drug
      release mechanism from the hydrogels. The values of the diffusion exponent 'n'
      have been obtained 0.5 for both swelling kinetics and drug release dynamics. This
      value shows that the Fickian type diffusion mechanism has occurred for the
      swelling of the polymers and for the release of drug from the polymers in
      different release mediums. The values of the initial diffusion coefficients (10.6
      x 10(-4), 13.1 x 10(-4), 14.0 x 10(-4))cm(2)/min, average diffusion coefficients
      (22.2 x 10(-4), 25.7 x 10(-4), 27.0 x 10(-4))cm(2)/min and late diffusion
      coefficients (1.68 x 10(-4), 2.15 x 10(-4), 2.28 x 10(-4))cm(2)/min for the
      release of tetracycline HCl respectively in distilled water, pH 2.2 buffer and pH
      7.4 buffer from the drug loaded samples shows that in the initial stages, the
      rate of release of drug from the hydrogels is slow and rate of diffusion of drug
      increases with time.

PMID- 18055145
TI  - Hypoglycemic and hypolipidemic effects of the aqueous fresh leaves extract of
      Clerodendrum capitatum in Wistar rats.
AB  - Diabetes mellitus, the most common endocrine disorder of carbohydrate metabolism,
      is treated in the African traditional phytotherapies with the cold water
      decoction of Clerodendrum capitatum (CC). In the current study, the hypoglycemic
      and hypolipidemic effects of fresh leaves aqueous extract of CC were studied in
      four groups of six adult Wistar rats per group and weighting 120-150 g, by
      administering graded oral doses (100, 400 and 800 mg/kg/day) of the extract for
      14 days. On the 15th day, the fasted rats were anesthetized under inhaled
      halothane and blood samples obtained through cardiac puncture. Phytochemical
      analysis of CC extract was conducted using standard procedures while the
      preliminary acute oral toxicity study was also conducted using limit dose test of
      Up and Down Procedure at a limit dose of 5000 mg/kg body weight/oral route.
      Results of the study showed CC to cause significant (p<0.05, p<0.001) dose
      dependent hypoglycemic and hypolipidemic effects but had no effect on the pattern
      of weight gain in the treated rats. Although no lethal effect was recorded with
      CC oral administration for up to 5000 mg/kg body weight/oral route, but there was
      an associated transient somatomotor and behavioral toxicities. Phytochemical
      results revealed the presence of saponins, flavonoids, alkaloids, tannin,
      glycosides and reducing sugars in the extract. Thus, the folkloric use of
      Clerodendrum capitatum in the treatment of suspected type 2 diabetics has a
      positive correlation with scientific data generated in this study.

PMID- 18055146
TI  - Ethnobotanical survey of folk plants for the treatment of snakebites in Southern
      part of Tamilnadu, India.
AB  - Ethnobotanical surveys were conducted in four different indigenous groups in
      Southern parts of Tamilnadu, India, using a questionnaire. The herbal
      practitioners in the study area were interviewed, and information on medicinal
      plants was collected from the traditional healers called "Vaidyars". This survey
      covers 72 medicinal plants belonging to 53 families that are used for the
      treatment of snakebite in a traditional way. Traditional approach was evaluated
      scientifically with some selected plant extracts (7.2 mg/kg bw) and partially
      purified fractions (2.4 mg/kg bw) were orally administered to mice experimentally
      envenomed with rattlesnake venom s.c. injection (2.5-15 microg/kg bw). Tested
      fractions (Aristolochia indica, Hemidesmus indicus, Gloriosa superba, Strychnos
      nux-vomica, Eclipta prostrata, and Andrographis paniculata) showed potent
      neutralizing effect against the venom. Compared to the extracts, administration
      of purified fractions was more effective in increasing the body weight. Control
      mice injected with the venom alone showed weight loss and severe toxicity at 15
      microg/kg bw. The purified fractions (2.4 mg/kg bw) produced significant
      protection against venom induced changes in serum SOD and LPx levels. The
      isolated fractions effectively inhibited the toxic effect of snake venoms in
      vitro than in vivo. The above observations confirmed the protective activity of
      plants-Aristolochia indica, Hemidesmus indicus, Gloriosa superba, Strychnos nux
      vomica, Eclipta prostrata, and Andrographis paniculata against the lethal action
      of snake venom and need further investigation.

PMID- 18055147
TI  - Acute and subchronic oral toxicity of Galega officinalis in rats.
AB  - Galega officinalis L. (Papilionaceae) is widely used in folk medicine as
      antidiabetic or for increasing lactation. There is a little information about its
      possible toxicity. In this study, acute and subchronic toxicity of aerial parts
      of Galega officinalis in Wistar rats have been evaluated. For the acute toxicity
      study, the animals received orally four different single dose of plant suspension
      and were kept under observation for 14 days. The results indicated that LD50 of
      Galega officinalis is higher than 5 g/kg. In the subchronic study, 48 rats were
      divided into four groups and were fed a diet containing 0%, 0.15%, 1.5% and 3%
      (w/w) of Galega officinalis. After 90 days blood and tissue samples were taken
      for hematological, biochemical and histopathological determinations. An increase
      in serum levels of cholesterol, creatine phosphokinase, lactate dehydrogenase and
      total and conjugated bilirubin was observed. Some parameters such as calcium,
      albumin, albumin/globulin ratio, hematocrit, WBC and platelet counts were
      decreased. In microscopic examination, sinusoidal congestion in liver and
      alveolar hemorrhage was observed. Other parameters showed non-significant
      difference between treatment and control groups. Present data suggest that liver
      and lung could serve as target organs in oral toxicity of this plant.

PMID- 18055148
TI  - An investigation into the relationship between edge counts and the variability of
      the refractive index of glass. Part I: Edge morphology.
AB  - The effect of glass fragment morphology on the variability of refractive index
      values in five different glass objects was investigated. Data are presented that
      suggest that the variability of refractive index values is increased when
      fragment edge morphology becomes unsuitable for phase contrast microscopy.

PMID- 18055149
TI  - [Retrospective census of cancers between 1994 and 2002 around the municipal solid
      waste incinerator of Gilly-sur-Isere].
AB  - BACKGROUND: The retrospective cancer incidence study carried out around the
      municipal solid waste incinerator of Gilly-sur-Isere (Savoie, France) was ordered
      in a context of crisis during its closing in the late 2001. Its purpose was to
      determine whether or not there was an excessive number of cancers around the
      incinerator. In the absence of cancer registry in Savoie, this study consisted in
      counting as exhaustively as possible the cancers that occurred between 1994 and
      2002 in the study area, which was exposed to the atmospheric fallouts from the
      incinerator. Thus, it was planned to compare the observed cancer incidence to the
      French cancer registries'. This work describes the main difficulties encountered
      as well as the solutions found during the census of cancer cases; the results of
      the incidence study are not included. METHODS: The collection of medical data was
      carried out thanks to multiple sources of information: pathology and hematology
      laboratories, hospitals' and clinics' departments of medical information, health
      insurance funds, liberal practitioners or specialised cancer registries. The
      collected medical data files were dealt with: looking for the missing addresses,
      selecting patients from the study area, homogenizing cancers coding, merging
      files into a single database, analysing available information on each cancer and
      de-duplicating the database. Most cancers were validated by consulting medical
      folders so as to exclude the false cases like metastasises of a known primary
      cancer or recurrences. RESULTS: Two thousand eight hundred and forty-five cancers
      were initially collected, and 28% of them were excluded because they did not
      correspond to the case definition (no proof of cancer, diagnosis date before the
      study period...); the final database was made of 2055 cancer cases. Quality
      indicators showed that the database could be considered as exhaustive and valid
      as a registry's. Three types of sources allowed to identify 94% of cases:
      laboratories, hospitals' departments of medical information and health insurance
      funds. CONCLUSION: Using administrative data and consulting medical folders
      turned out to be necessary considering uncertainties about: the patients'
      residence at the time of the diagnosis, errors in coding cancers in some
      databases that were collected and difficulties to identify false cases. This
      census required very important means.

PMID- 18055150
TI  - Value of conventional chest radiography for the detection of coronary
      calcifications: comparison with MSCT.
AB  - PURPOSE: To evaluate if computed tomography (CT) coronary calcium scoring is
      needed after detection of coronary calcifications on conventional chest
      radiographs. MATERIALS AND METHODS: One hundred and five patients (67 men; 57.2+/
      12.8 years) with suspected coronary artery disease underwent conventional chest
      radiography and non-enhanced, retrospectively ECG-gated multislice spiral CT
      (MSCT) of the heart (4 mm x 2.5 mm, 120 kV, 133 mAs(eff.)). Chest radiographs
      were assessed independently by two radiologists. Detection of coronary
      calcifications was compared between both methods. Sensitivity, specificity,
      negative and positive predictive values, median, 25% and 75% percentiles for the
      detection of coronary calcifications were calculated. Receiver operating
      characteristics (ROC) analyses were computed. RESULTS: In 90 patients, MSCT
      revealed coronary calcifications. The mean coronary calcium score was 526.2 (0
      4784.5). On chest radiographs, coronary calcifications were correctly detected in
      46 (61) patients by observer 1 (observer 2). The corresponding sensitivity was
      51.1% in observer 1 and 67.8% in observer 2. Median of detected coronary
      calcifications was 361.9 (426.4) for observer 1 (observer 2). Corresponding 25%
      und 75% percentiles were 109.6 (109.6) and 798.5 (898.5). The area under the ROC
      curve was 0.636 for observer 1 and 0.715 for observer 2. There was no correlation
      between image quality and the detection of coronary calcifications on plain film
      radiographs. CONCLUSION: As coronary calcifications of various extents are
      inconsistently detected on plain chest radiographs, CT calcium scoring may not be
      omitted even if coronary artery calcifications were detected on conventional
      chest radiographs.

PMID- 18055151
TI  - The prevalence and clinical predictors of incidental atherosclerotic renal artery
      stenosis.
AB  - OBJECTIVE: To evaluate the prevalence of incidental renal artery stenosis due to
      atherosclerosis and associated risk factors in patients with peripheral arterial
      disease (PAD). MATERIALS AND METHODS: To determine renal artery stenosis,
      aortofemoropopliteal digital substraction angiographies (DSA) of 629 consecutive
      patients with PAD were prospectively reviewed. Angiographies were performed as
      catheter angiography with automated pump injection. Of the patients, 540 were
      male (86%) and 89 female (14%) (mean age+/-S.D.: 61.5+/-11.1 years). Statistical
      analysis was performed to determine the association of significant renal artery
      stenosis (> or =60% diameter stenosis) with patient demographics (age, sex,
      reason for angiography and smoking status), medical history (diabetes mellitus,
      hypertension and coronary artery disease), laboratory values (blood creatinine,
      fasting glucose, triglycerides, LDL, HDL and total cholesterol) and distribution
      of PAD (aortoiliac, femoropopliteal and crural diseases and multisegment
      involvement). RESULTS: Renal artery disease was found in 33% (207 of 629) of all
      patients with peripheral arterial disease, and 9.6% of patients (n=60) had
      significant (> or =60%) renal artery stenosis. Only age and hypertension (blood
      pressure systolic >140 mmHg or diastolic >90 mmHg) were independent risk factors
      for significant renal artery stenosis on multivariate analysis. Mean age of
      patients with RAS was 66.5+/-8.9 years compared with 61+/-11.2 years for patients
      without RAS (p<0.001). Hypertension was found in 41% of the patients in control
      group and in 63% of the patients in RAS group (p=0.01). CONCLUSION: Incidental
      renal artery stenosis which can be mild or significant is a relatively common
      finding among patients with peripheral arterial disease. Advance age and
      hypertension are closely associated with significant renal artery stenosis.

PMID- 18055153
TI  - Study of equilibrium solubility measurement by saturation shake-flask method
      using hydrochlorothiazide as model compound.
AB  - The experimental conditions that affect equilibrium solubility values measured by
      the classical saturation shake-flask method have been examined, using
      hydrochlorothiazide as a model compound. Modifications in temperature,
      sedimentation time, composition of aqueous buffer and the technique of separation
      of solid and liquid phases were all found to influence the equilibrium solubility
      results strongly. However, variations in the amount of solid excess and stirring
      time were found to have less influence. In the light of these observations, a
      new, shorter protocol has been developed for measurements of equilibrium
      solubility, together with recommendations for good analytical practice. The
      equilibrium solubilities of five other drugs were measured to verify the new
      protocol.

PMID- 18055152
TI  - Renal transplant failure due to urologic complications: Comparison of static
      fluid with contrast-enhanced magnetic resonance urography.
AB  - PURPOSE: Postrenal reasons of renal transplant failure can be assessed by
      magnetic resonance urography. This study was designed to retrospectively compare
      the diagnostic accuracy of static fluid (T2-)MRU compared to contrast enhanced
      (CE-)MRU in patients with renal transplant failure. MATERIAL AND METHODS: Thirty
      five consecutive patients (14 female, 21 men; mean age 48.6 years) with renal
      transplant failure and sonographically detected hydronephrosis were examined both
      with T2-MRU as well as CE-MRU resulting in 39 MRU examinations. MRU was performed
      both using T2-weighted HASTE-sequence (T2-MRU) as well as Gadolinium-enhanced 3D
      FLASH-sequence (CE-MRU) on a 1.5-T clinical MRI scanner (Magnetom Vision, Siemens
      Medical Solutions). Subjective image quality of resulting maximum intensity
      projection was assessed in consensus by two readers blinded to the final
      diagnosis, using a five point scale. MRU findings were correlated to sonography,
      operative results or clinical follow up. RESULTS: CE-MRU yielded a sensitivity of
      85.7% (T2-MRU 76.2%), and a specificity of 83.3% (T2-MRU: 73.7%), however
      statistical significance was not reached. The subjective image quality was
      significantly better in CE-MRU. CONCLUSIONS: Only concerning subjective image
      quality CE-MRU proved superior to T2-MRU. Yet, there was no significant
      difference in diagnostic accuracy between T2- and CE-MRU. Thinking of incipient
      nephrogenic systemic fibrosis, T2-MRU can be used as reliable alternative in
      patients with decreased renal transplant function due to urological
      complications.

PMID- 18055154
TI  - Capillary electrophoresis for short chain organic acids in faeces Reference
      values in a Mediterranean elderly population.
AB  - There is increasing evidence that gut microflora and fermentation processes in
      the large intestine are important for health, and that health-promoting effects
      are mediated by fermentation products. Usually analytical methods for these
      compounds are tedious. A simple and rapid procedure of aqueous extraction from
      the stools has been optimized. After extraction, an aliquot of the aqueous layer
      was directly injected into the capillary electrophoresis equipment. Oxalic,
      formic, fumaric, 2-ketoglutaric, succinic, citric, acetic, propionic, 2
      ketoisovaleryc, butyric, isovaleric lactic, glyceric 2-hydroxybutyric, and
      valeric acids were separated and identified. Electrophoretic conditions were:
      phosphate buffer 234 mM pH 6.10 with 12% (v/v) methanol with a coated capillary
      at -10 kV of applied potential. The method was validated for a representative
      group of compounds: acetic, propionic butyric, 2-hydroxybutiric, isovaleric, and
      oxalic acids, including the comparison of results with ionic chromatography.
      Finally 136 samples from healthy humans aged 60-80, both male and female living
      in Spain, were measured. They could be used as reference values for further
      studies.

PMID- 18055155
TI  - HPLC determination of rifampicin and related compounds in pharmaceuticals using
      monolithic column.
AB  - A rapid, sensitive and reproducible HPLC method using C18 monolithic column was
      developed and validated for the analysis of rifampicin (RIF) and its four related
      compounds, including rifampicin quinone (RQ), rifamycin SV (SV), rifampicin N
      oxide (RNO) and 3-formylrifamycin SV (3-FR). Chromatographic separation was
      achieved by using the mixture of methanol-acetonitrile-monopotassium phosphate
      (0.075 M)-citric acid (1.0M) (28:30:38:4, v/v) as the mobile phase at a flow rate
      of 2 mL/min and with UV detection at 254 nm. Calibration curves were obtained in
      the concentration ranges of 1-40 microg/mL for SV, RNO and 3-FR, 1.5-60 microg/mL
      for RQ and 5-200 microg/mL for RIF. Limit of quantitation (LOQ) was determined to
      be 1 microg/mL and the limit of detection (LOD) was 0.2 microg/mL for all studied
      compounds with a 10 microL injection. The intra-day R.S.Ds. and inter-day R.S.Ds.
      for the above five compounds were all less than 2.5%. The recoveries of
      rifampicin from placebo tablets were from 99.7% to 100.5%. The total run time was
      less than 11 min, as opposed to around 60 min by using C18 particle-packed
      column. In conclusion, by this developed method, RIF and its related compounds
      can be determined rapidly with good precision and accuracy in pharmaceuticals.

PMID- 18055156
TI  - Advances in development of transgenic pulse crops.
AB  - It is three decades since the first transgenic pulse crop has been developed.
      Todate, genetic transformation has been reported in all the major pulse crops
      like Vigna species, Cicer arietinum, Cajanus cajan, Phaseolus spp, Lupinus spp,
      Vicia spp and Pisum sativum, but transgenic pulse crops have not yet been
      commercially released. Despite the crucial role played by pulse crops in tropical
      agriculture, transgenic pulse crops have not moved out from laboratories to large
      farm lands compared to their counterparts - 'cereals' and the closely related
      leguminous oil crop - 'soybean'. The reason for lack of commercialization of
      transgenic pulse crops can be attributed to the difficulty in developing
      transgenics with reproducibility, which in turn is due to lack of competent
      totipotent cells for transformation, long periods required for developing
      transgenics and lack of coordinated research efforts by the scientific community
      and long term funding. With optimization of various factors which influence
      genetic transformation of pulse crops, it will be possible to develop transgenic
      plants in this important group of crop species with more precision and
      reproducibility. A translation of knowledge from information available in
      genomics and functional genomics in model legumes like Medicago truncatula and
      Lotus japonicus relating to factors which contribute to enhancing crop yield and
      ameliorate the negative consequences of biotic and abiotic stress factors may
      provide novel insights for genetic manipulation to improve the productivity of
      pulse crops.

PMID- 18055157
TI  - Interleukin-4 increases cortisol release and decreases adrenal androgen release
      from bovine adrenal cells.
AB  - ACTH is the primary regulator of adrenal function during acute stress. However,
      during chronic inflammatory stress additional factors play a major role in the
      regulation of adrenal secretion. Many cytokines circulate in the blood and are
      synthesized and released from adrenal tissue. Furthermore, these peptides modify
      adrenal function. Recently, interleukin-4 (IL-4) was demonstrated to be released
      from a human adrenal tumor cell line. Therefore, we hypothesized that normal
      bovine adrenocortical cells could express IL-4 and that this cytokine may modify
      adrenal function. We determined that IL-4 and IL-4 receptors (IL-4R) are
      expressed in the bovine adrenal cortex whereas the expression of IL-4 and IL-4R
      in the adrenal medulla was not apparent. Exposure of dispersed bovine
      adrenocortical cells isolated from the zona fasciculate to IL-4 did not modify
      basal release of cortisol. However, the ACTH-stimulated release of cortisol from
      the bovine adrenal cells was augmented by IL-4. IL-4 exposure had no affect on
      adrenal androgen release from bovine zona reticularis cells, but IL-4 inhibited
      the ACTH-stimulated release of adrenal androgens from these cells. The effects of
      IL-4 on ACTH-stimulated cortisol and adrenal androgen release were dependent upon
      the IL-4 incubation interval and the IL-4 concentration. Because communication
      between the immune and endocrine systems is important in inflammatory conditions,
      IL-4 may play a role in coordinating the adrenal response to inflammatory stress.

PMID- 18055158
TI  - Thermal ablation of hepatic malignancy: useful but still not optimal.
AB  - The mortality associated with primary and metastatic hepatic malignancies remains
      high because few patients are candidates for hepatic resection or
      transplantation. Resection is the most effective treatment for liver tumors but
      may be contraindicated by factors such as the tumor's location; hepatic
      transplantation can cure primary hepatocellular carcinoma and underlying
      cirrhosis, but a donor may not be immediately available. When resection or
      transplantation is not possible, thermal ablation is a reasonable therapeutic
      option. Effective destruction of tumors can be achieved with low recurrence rates
      and minimal complications or risk of death. In patients with primary hepatic
      malignancy, ablation treatment does not preclude subsequent transplantation.
      Although radiofrequency ablation is currently the most widely used thermal
      ablative technique for hepatic malignancy, microwave ablation is gaining
      popularity and eventually may prove to be more effective.

PMID- 18055159
TI  - [Surveillance during the postoperative period].

PMID- 18055160
TI  - Lifestyle-related factors and environmental agents causing cancer: an overview.
AB  - The increasing incidence of a variety of cancers after the Second World War
      confronts scientists with the question of their origin. In Western countries,
      expansion and ageing of the population as well as progress in cancer detection
      using new diagnostic and screening tests cannot fully account for the observed
      growing incidence of cancer. Our hypothesis is that environmental factors play a
      more important role in cancer genesis than it is usually agreed. (1) Over the
      last 2-3 decades, alcohol consumption and tobacco smoking in men have
      significantly decreased in Western Europe and North America. (2) Obesity is
      increasing in many countries, but the growing incidence of cancer also concerns
      cancers not related to obesity nor to other known lifestyle-related factors. (3)
      There is evidence that the environment has changed over the time period preceding
      the recent rise in cancer incidence, and that this change, still continuing,
      included the accumulation of many new carcinogenic factors in the environment.
      (4) Genetic susceptibility to cancer due to genetic polymorphism cannot have
      changed over one generation and actually favours the role of exogenous factors
      through gene-environment interactions. (5) Age is not the unique factor to be
      considered since the rising incidence of cancers is seen across all age
      categories, including children, and adolescents. (6) The fetus is specifically
      vulnerable to exogenous factors. A fetal exposure during a critical time window
      may explain why current epidemiological studies may still be negative in adults.
      We therefore propose that the involuntary exposure to many carcinogens in the
      environment, including microorganisms (viruses, bacteria and parasites),
      radiations (radioactivity, UV and pulsed electromagnetic fields) and many
      xenochemicals, may account for the recent growing incidence of cancer and
      therefore that the risk attributable to environmental carcinogen may be far
      higher than it is usually agreed. Of major concern are: outdoor air pollution by
      carbon particles associated with polycyclic aromatic hydrocarbons; indoor air
      pollution by environmental tobacco smoke, formaldehyde and volatile organic
      compounds such as benzene and 1,3 butadiene, which may particularly affect
      children and food contamination by food additives and by carcinogenic
      contaminants such as nitrates, pesticides, dioxins and other organochlorines. In
      addition, carcinogenic metals and metalloids, pharmaceutical medicines and some
      ingredients and contaminants in cosmetics may be involved. Although the risk
      fraction attributable to environmental factors is still unknown, this long list
      of carcinogenic and especially mutagenic factors supports our working hypothesis
      according to which numerous cancers may in fact be caused by the recent
      modification of our environment.

PMID- 18055161
TI  - [Severe asthma].
AB  - Severe asthma is diagnosed in patients with refractory asthma that is difficult
      to control despite a thorough reevaluation of the diagnosis and management and
      after more than 6 months of follow-up by a physician specializing in asthma.
      Respiratory function measurements and reversibility and bronchial provocation
      tests (except when contraindicated) are essential in the reevaluation of an
      asthma diagnosis. Factors that can influence asthma control, such as
      environmental exposures, comorbid conditions, treatment adherence, and in
      particular inhalation technique must be recognized and considered appropriately
      before confirming the diagnosis of severe asthma. Objective criteria are
      important in the follow-up evaluation of severe asthma. They must include the
      measurement of some disease components. During follow-up, it is recommended that
      patients be monitored by validated questionnaires about quality of life and
      asthma control and by pulmonary function measurements, airway inflammation
      assessment, and recording the frequency of exacerbations and healthcare system
      use (including whether planned or unexpected). Severe asthma is a heterogeneous
      condition that includes several phenotypes. Determining the phenotype of each
      case of severe asthma will improve our understanding of its underlying
      mechanisms, natural history and prognosis, will help guide the choice of current
      and future treatments and will provide useful indications for new therapeutic
      interventions.

PMID- 18055162
TI  - [Severe hard-to-treat refractory asthma: the only asthma issue of the 21st
      century?].

PMID- 18055163
TI  - Using a clinically aggressive sample to examine the association between
      impulsivity, executive functioning, and verbal learning and memory.
AB  - Impulsive behavior has been conceptualized from several vantage points including
      biological, sociological and psychological phenomenon. A comprehensive review of
      the empirical literature revealed that there is a paucity of research examining
      the association between working memory, executive functioning and impulsivity. A
      total sample of 170 aggressive outpatient participants was recruited for the
      study. Participants were administered a comprehensive neuropsychological battery.
      Principal components analysis of the 19 CVLT indices revealed five factors,
      accounting for 68% of the total variance. Results from the canonical correlation
      revealed one significant canonical variate with loadings from three CVLT factors
      (General Verbal Learning, Response Discrimination, and Proactive Interference),
      two executive functioning measures (Trail Making Test and Controlled Oral Word
      Association Test), and one impulsivity subscale (Attentional Impulsiveness). The
      findings of this study underscore the importance of memory functioning in
      determining impulsive aggressive behavior.

PMID- 18055164
TI  - Origin and spread of the SRY gene on the X and Y chromosomes of the rodent
      Microtus cabrerae: role of L1 elements.
AB  - In the rodent species Microtus cabrerae, males as well as females present several
      copies of the SRY gene, a single-copy gene located on the Y chromosome in most
      mammals. Using different PCR approaches, we have characterized the sequence,
      structure, and organization of the SRY copies and their flanking regions
      distributed on the X and Y chromosomes of this species. All copies of SRY
      analyzed, including those from the Y chromosome, proved to be nonfunctional
      pseudogenes, as they have internal stop codons. In addition, we demonstrated the
      association of SRY pseudogenes with different fragments of L1 and LTR
      retroelements in both sex chromosomes of M. cabrerae. Examining the possible
      origin of SRY pseudogene and retroposons association, we propose that retroposons
      could have been involved in the mechanism of SRY gene amplification on the Y
      chromosome and in the transference of the Y-linked SRY copies to the X-chromosome
      heterochromatin.

PMID- 18055167
TI  - Aortoiliac occlusive disease in the presence of a horseshoe kidney: a case
      report.
AB  - A case of aortoiliac occlusive disease in the presence of a horseshoe kidney
      anomaly is presented. The importance of careful preoperative planning by way of
      specialized investigations is stressed and the merits of both the anterior
      transperitoneal and retroperitoneal approaches to aortoiliac reconstruction in
      the presence of a horseshoe kidney are outlined.

PMID- 18055165
TI  - Expression profiling identifies novel Hh/Gli-regulated genes in developing
      zebrafish embryos.
AB  - The Hedgehog (Hh) signaling pathway plays critical instructional roles during
      embryonic development. Misregulation of Hh/Gli signaling is a major causative
      factor in human congenital disorders and in a variety of cancers. The zebrafish
      is a powerful genetic model for the study of Hh signaling during embryogenesis,
      as a large number of mutants that affect different components of the Hh/Gli
      signaling system have been identified. By performing global profiling of gene
      expression in different Hh/Gli gain- and loss-of-function scenarios we identified
      known (e.g., ptc1 and nkx2.2a) and novel Hh-regulated genes that are
      differentially expressed in embryos with altered Hh/Gli signaling function. By
      uncovering changes in tissue-specific gene expression, we revealed new
      embryological processes that are influenced by Hh signaling. We thus provide a
      comprehensive survey of Hh/Gli-regulated genes during embryogenesis and we
      identify new Hh-regulated genes that may be targets of misregulation during
      tumorigenesis.

PMID- 18055166
TI  - Social networks and immunosuppression during stress: relationship conflict or
      energy conservation?
AB  - Despite the apparent health benefits of social relationships, some studies
      indicate that larger social networks can be associated with greater vulnerability
      to infectious disease, particularly if stressors are also present. Two
      possibilities for such effects are, first, that more social contacts lead to more
      negative affect and social conflict during stressors, or second, that maintaining
      more social contacts is an energetically costly activity, and ecologically
      motivated immunosuppression is one means of providing energy to maintain social
      resources. First-year law students (N=76) completed questionnaires and had
      delayed-type hypersensitivity skin tests at five time points during their first 6
      months of law school. Both moving away from home and a smaller social network
      associated with larger DTH responses (both p<0.05) across all time points.
      However, negative affect, either broadly defined or as specific affects
      (hostility, sadness, guilt), did not mediate social network effects, suggesting
      that negative affect and social conflict are less plausible explanations than
      ecological immunosuppression. Ecological models would predict that temporary
      immunosuppression is less harmful to health in the long run than loss of social
      resources.

PMID- 18055168
TI  - Improved outcome after rupture of abdominal aortic aneurysm over an 18-year
      period.
AB  - The purpose of the study was to analyze changes in in-hospital mortality of
      patients with ruptured abdominal aortic aneurysm (RAAA) during an 18-year period.
      A retrospective analysis of 246 patients with RAAA in the years 1987-2005 was
      performed. The patients were divided into groups that consisted of 111 patients
      treated in the years 1987-2000 (group I) and 135 patients treated in the years
      2001-2005 (group II). The in-hospital mortality rates of all patients and of
      operated patients in both groups were analyzed. Preoperative variables such as
      age, gender, size of the aneurysm, duration of symptoms, distance to the vascular
      surgery department, full blood count, serum creatinine and urea concentrations,
      and systolic and diastolic blood pressures, as well as the number of all AAAs and
      RAAAs treated per year, were compared between the groups. The Mann-Whitney U-test
      and Fisher exact test were used to analyze differences in continuous and
      categorical variables, respectively. The in-hospital mortality of all patients
      was significantly lower in group II (p = 0.006) The difference in in-hospital
      mortality of operated patients was of borderline statistical significance (p =
      0.07). The proportion of nonoperated patients decreased from 21% to 6% (p =
      0.0008). The patients from group II had significantly higher preoperative levels
      of hemoglobin, hematocrit, erythrocytes, and platelets, as well as higher
      systolic and diastolic blood pressure and smaller diameter of aneurysm. The
      number of both all aneurysms and RAAAs per year was significantly higher in group
      II. The improved preoperative status of the patients and more aggressive surgical
      approach are associated with reduction in in-hospital mortality of patients with
      RAAA. The increased experience of the center may also improve outcome of RAAA.

PMID- 18055169
TI  - Positional symptomatic occlusion of the internal carotid artery: evaluation and
      surgical management.
AB  - A 42-year-old woman developed right arm and right leg weakness when turning her
      head to the left. A carotid angiogram, in the neutral position, demonstrated
      anterior deviation of the left internal carotid artery and complete occlusion of
      the left internal carotid artery when the head was rotated to the left. During
      surgery, our patient had redundant left internal carotid artery and was treated
      by resection and reanastomosis of the internal carotid artery. The patient's
      Doppler 4 months postoperatively showed widely patent arteries, and she has
      subsequently been asymptomatic.

PMID- 18055170
TI  - Ultrasound screening for abdominal aortic aneurysm in medicare beneficiaries.
AB  - Ultrasound screening for abdominal aortic aneurysm (AAA) has been shown to be
      beneficial and cost-effective for men aged 65-74. However, most screening studies
      have been conducted in Europe and Australia, where attendance for screening was
      higher than the single large U.S. study involving only veterans. The prevalence
      of AAA in the U.S. general population is not well defined, nor is the best method
      of recruitment for screening. Letters of invitation for a free screening
      ultrasound for AAA were sent to 30,000 randomly selected Medicare beneficiaries
      from the hospital referral region of three university-affiliated hospitals
      without restriction by age, gender, or comorbidity. Attendance for screening was
      calculated by age, gender, and travel distance to the screening center. Telephone
      calls to a random sample of nonresponders were made to determine the reason for
      failure to attend. Prevalence of AAA by ultrasound and known risk factors for AAA
      (e.g., age, gender, smoking status) were determined. The attendance rate was 7%
      (2,005). Attendance was greater with male gender (p < 0.01), younger age (p <
      0.05), and decreased travel distance to the screening center (p < 0.05). The
      primary reasons for failure to attend included incorrect address or vital status,
      poor health, and lack of interest. Prevalence of previously undetected AAA was
      2.8% in men and 0.2% in women. AAA was predicted by smoking status and male
      gender (p < 0.01 for each). Unselected invitation of Medicare beneficiaries for
      ultrasound screening for AAA results in a low attendance and low yield of AAA.
      The prevalence estimates from this study may not reflect the entire Medicare
      population given the low attendance and may reflect the healthy habits of those
      most interested in screening. Patients should be selected for screening based on
      their suitability for repair if an AAA is found as well as their risk factors for
      AAA. The best method of recruitment for screening of those most at risk for AAA
      in the United States remains to be determined.

PMID- 18055171
TI  - The effect of systemic anticoagulation in patients undergoing angioaccess
      surgery.
AB  - The benefit of intravenous heparin as an anticoagulant to avoid thrombotic
      complications during angioaccess surgery for hemodialysis is unknown. We
      prospectively randomized 115 consecutive patients referred to our institution for
      permanent hemodialysis access to receive systemic anticoagulation or no
      anticoagulation during angioaccess surgery. Patient demographics, comorbid
      conditions, procedure time, complications, and patency were recorded in
      accordance with standards recommended by the Society for Vascular Surgery. Of the
      115 patients randomized, 58 received no anticoagulation and 57 received systemic
      anticoagulation with intravenous heparin. Arteriovenous fistulas were created in
      84 patients and 31 arteriovenous grafts were inserted. Operative times were
      longer for grafts compared to fistulas, but there were no significant differences
      in operative times between patients receiving anticoagulation and those not (p =
      0.31). Perioperative bleeding complications were more common in patients
      receiving heparin (p = 0.008). The primary 30-day patency was 84% for patients
      receiving heparin and 86% for those not (p = 0.79). The 3-month functional
      patency was 68% for both groups (p = 0.99). Age, gender, operative time, and
      incidence of bleeding complications had no impact on patency. In our experience,
      systemic anticoagulation for angioaccess surgery is associated with an increased
      incidence of bleeding complications and offers no advantage in terms of early
      patency.

PMID- 18055172
TI  - Femororenal arteriovenous graft: a viable option for hemodialysis access.
AB  - There has been a significant increase in the number of patients with end-stage
      renal disease. The limited number of kidney transplants necessitates that most
      patients become dependent upon chronic dialysis. Due to the numerous
      complications associated with temporary access catheters, permanent arteriovenous
      access is more beneficial for long-term vascular access. However, with the
      restricted availability of sites for permanent vascular access, it is important
      to have a variety of possibilities. In this case report, we present an
      alternative choice for an arteriovenous graft, left common femoral artery to left
      renal vein, in a patient with limited vascular access options.

PMID- 18055173
TI  - Renal response to open and endovascular repair of abdominal aortic aneurysm: a
      prospective study.
AB  - Because of incompatible reports about the renal impairment to abdominal aortic
      aneurysm (AAA) repair, we conducted a prospective study to determine the
      differences in renal response between open (OR) and endovascular (EVAR) aneurysm
      repair. In a prospective, nonrandomized, single-center study, we evaluated 485
      patients with AAAs undergoing OR or EVAR between January 2000 and December 2005.
      Only electively performed procedures were analyzed in detail. The OR group
      included 229 patients (males/females 203/26, median age 69.8 [range 43-90] years,
      aneurysm diameter in median 57 [26-95] mm), and the EVAR group integrated 144
      patients (males/females 129/15, 73.1 [49-90] years [p=.001], 55 [33-100] mm).
      Renal function was assessed by determinating the preoperative serum creatinine
      (SCr) level and SCr clearance according to Cockcroft-Gault. Postoperatively, SCr
      level and SCr clearance were determined at defined intervals, reported as highest
      postoperative SCr level, SCr level at time of discharge, lowest postoperative SCr
      clearance, and SCr clearance at time of discharge. The parameters of height,
      weight, diabetes, smoking habit, serum cholesterol level, and hemoglobin were not
      different between the groups. Significantly different were the American Society
      of Anesthesiologists classification, the Society for Vascular Surgery Comorbidity
      Score, and the exposure to contrast dye. Moreover, significantly different were
      intraoperatively measured median blood loss (1,200 vs. 400 mL) and the median
      time of operation (164 vs. 135 min). Although, the preoperative SCr levels
      between the groups were not statistically different (OR group 1.0 [0.87-1.23]
      mg/dL [median, interquartile range], EVAR group 1.0 [0.9-1.3]; p > 0.05), the SCr
      clearance was (OR group 72.8 [58.2-98.8] mL/min, EVAR group 67.6 [51.3-85.1]
      mL/min; p = 0.007). In the postoperative period, SCr level did not change
      significantly in the OR group but did in the EVAR group to a level of 1.08 (0.9
      1.36) mg/dL (p = 0.007). Similarly, SCr clearance decreased significantly in the
      EVAR group to a level of 66.7 (49.9-81.4) mL/min. These results were influenced
      by the stent graft design (deployment under the renal arteries vs. covering the
      renals with bared stents). Mortality was 3/229 in the OR group and 4/144 in the
      EVAR group. Acute renal impairment occurred in a subset of patients with AAAs
      with regard to the type of repair. EVAR showed a slight deterioration of renal
      function, but the evaluated tests are insensitive and without prognostic value
      concerning mortality or hospitalization. More sensitive markers of the
      differentiated renal functions (cystatin C for renal glomerular function, N
      acetyl-ss-d-glucosamidase for proximal tubular function) should be evaluated in
      future studies.

PMID- 18055175
TI  - Missing data: implications for analysis.

PMID- 18055174
TI  - A novel method for automatic determination of different stages of multiple
      sclerosis lesions in brain MR FLAIR images.
AB  - It is very important to detect stages of multiple sclerosis (MS) lesions in order
      to exactly quantify involved voxels. In this paper, a novel method is proposed
      for automatic detection of different stages of MS lesions in the brain magnetic
      resonance (MR) images, in fluid attenuated inversion recovery (FLAIR) studies. In
      the proposed method, firstly, MS lesion voxels are segmented in FLAIR images
      based on adaptive mixtures method (AMM) and Markov Random Field (MRF) model.
      Then, signal intensity of each lesion voxel is modeled as a linear combination of
      signals related to the normal and also abnormal parts, in the voxel. By applying
      an optimal threshold, voxels with new intensities are primarily classified into
      two stages: previously destructed (chronic) and on going destruction (acute)
      lesions. Finally, the acute lesions, according to their activities, are
      classified, by another optimal threshold, into two new stages, early and recent
      acute. Evaluation of the proposed method was performed by manual segmentation of
      chronic and enhanced (early) acute lesions in gadolinium enhanced T1-weighted
      (Gad-E-T1-w) images by studying T1-weighted (T1-w) and T2-weighted (T2-w) images,
      using similarity criteria. The results showed a good correlation between the
      lesions segmented by the proposed method and by experts manually. Thus, the
      suggested method is useful to reduce the need for paramagnetic materials in
      contrast enhanced MR imaging which is a routine procedure for separation of acute
      and chronic lesions.

PMID- 18055176
TI  - Deficits in facial affect recognition in unaffected siblings of Xhosa
      schizophrenia patients: evidence for a neurocognitive endophenotype.
AB  - The present study in an African Xhosa sample examined whether familial
      vulnerability to schizophrenia is associated with deficits in facial affect
      recognition. Healthy comparison subjects, unaffected siblings of schizophrenia
      patients, and schizophrenia patients were tested with a task requiring rapid
      recognition of matched positive (happy), negative (angry), and neutral facial
      expressions. Siblings and patients demonstrated impaired recognition of negative
      relative to positive facial expressions whereas comparison subjects recognized
      negative and positive expressions at an equal level of accuracy. These results
      suggest that deficits in the processing negative affect from social cues are
      transmitted in families and may represent a heritable endophenotype of
      schizophrenia.

PMID- 18055177
TI  - Depression in schizophrenia: comparison of first- and second-generation
      antipsychotic drugs.
AB  - The aim of this study was to compare the effects of different antipsychotics on
      depressive symptoms in schizophrenic patients. The data were drawn from a
      retrospective, naturalistic, observational study in which 222 subjects diagnosed
      as being affected by schizophrenia during a re-exacerbation phase received 6
      weeks of monotherapy with fluphenazine decanoate, haloperidol decanoate,
      haloperidol, clozapine, olanzapine, quetiapine, risperidone or l-sulpiride. The
      Brief Psychiatric Rating Scale (BPRS), Extrapyramidal Side Effects Rating Scale
      (EPSE) and Anticholinergic Rating Scale (ACS) were administered at baseline and
      six weeks after the beginning of the study; depressive symptoms were evaluated
      using the BPRS items "depressive mood" and "guilt feelings". All of the
      antipsychotic drugs led to improvements in the depressive dimension, but this was
      statistically significant only in the case of fluphenazine decanoate,
      haloperidol, olanzapine, risperidone and l-sulpiride. A clinical improvement in
      the depressive dimension significantly correlated with the severity of the
      psychotic picture and its amelioration. Female patients were significantly more
      likely to show an improvement in depressive symptoms. In conclusion, our findings
      suggest that atypical antipsychotics as a class do not seem to be more effective
      on the depressive dimension during the course of schizophrenia than typical ones,
      at least as far as the collected BPRS data are concerned. The only factor that
      seemed to influence the improvement in depressive symptoms during our study was
      gender, as females were significantly more likely to improve although there were
      no between-gender differences in the baseline severity of the clinical picture.

PMID- 18055178
TI  - Neuropsychological substrates and everyday functioning implications of
      prospective memory impairment in schizophrenia.
AB  - Individuals with schizophrenia demonstrate impairment in prospective memory
      (ProM), which describes the multifaceted ability to execute a future intention.
      Despite its clear implications for everyday functioning, the neuropsychological
      substrates and functional correlates of ProM impairment in schizophrenia remain
      poorly understood. In this study, the Memory for Intentions Screening Test
      (MIST), a standardized measure of ProM, was administered to 72 outpatients with
      schizophrenia or schizoaffective disorder as part of a comprehensive
      neuropsychological and psychiatric research evaluation. Results showed that ProM
      was positively correlated with standard clinical tests of attention, working
      memory, processing speed, learning, and executive functioning, but not delayed
      recall. In the context of multiple neuropsychological predictors, learning
      ability was the only domain that independently contributed to ProM. Importantly,
      better ProM was predictive of higher functional capacity (as measured by the UCSD
      Performance-Based Skills Assessment-Brief Version), above and beyond the
      variability explained by demographic and disease factors. Analysis of component
      processes revealed that event-based ProM, as well as no response (i.e., omission)
      and task substitution errors were the strongest predictors of everyday
      functioning. Overall, these findings suggest that ProM impairment in
      schizophrenia is associated with multiple cognitive substrates, particularly
      episodic learning deficits, and plays an important role in everyday living
      skills. Studies regarding the potential effectiveness of ProM-based remediation
      strategies to improve functional outcomes in schizophrenia are indicated.

PMID- 18055179
TI  - Pathways to psychosis: a comparison of the pervasive developmental disorder
      subtype Multiple Complex Developmental Disorder and the "At Risk Mental State".
AB  - BACKGROUND: The comparison of high-risk populations with different developmental
      pathways to psychosis may lend more insight into the heterogeneity of the
      manifestation of the psychotic syndrome, and possible differing etiological
      pathways. AIM: To compare high-risk traits and symptoms in two populations at
      risk for psychosis, i.e. (1) help-seeking adolescents presenting with prodromal
      symptoms meeting the criteria for At Risk Mental State (ARMS), and (2)
      adolescents with Multiple Complex Developmental Disorder (MCDD), a PDD-NOS
      subtype characterized by severe, early childhood-onset deficits in affect
      regulation, anxieties, disturbed social relationships, and thought disorder.
      METHOD: 80 ARMS- and 32 MCDD-adolescents (12-18 years) were compared on prodromal
      symptoms (Structured Interview of Prodromal Symptoms, and Bonn Scale for the
      Assessment of Basic Symptoms-Prediction list), and autism traits (Social
      Communication Questionnaire). In addition, both high-risk groups were compared
      with 82 healthy controls on schizotypal traits (Schizotypal Personality
      Questionnaire-Revised). RESULTS: Although the high-risk groups clearly differed
      in early developmental and treatment histories as well as autism traits, they did
      not differ with regard to schizotypal traits and basic symptoms, as well as
      disorganized and general prodromal symptoms. There were, however, group
      differences in positive and negative prodromal symptoms. Interestingly, 78% of
      the adolescents with MCDD met criteria for ARMS. CONCLUSION: These findings
      suggest that children diagnosed with MCDD are at high risk for developing
      psychosis later in life, and support the notion that there are different
      developmental pathways to psychosis. Follow-up research is needed to compare the
      rates of transition to psychosis in both high-risk groups.

PMID- 18055180
TI  - Evolution of neuroleptic-induced extrapyramidal syndromes under long-term
      neuroleptic treatment.
AB  - BACKGROUND: The long-term evolution of neuroleptic-induced extrapyramidal
      syndromes (EPS) of Parkinsonism, akathisia and tardive dyskinesia (TD) is still a
      controversial issue worth exploring. METHOD: A total of 200 inpatients on regular
      typical neuroleptics (NL) and/or clozapine were assessed in 1995 with regard to
      the prevalence of EPS. Altogether, 83 patients could be reassessed in 2003/04 (63
      had died) using the same methods. Strict definitions of EPS were used. The
      complete account of NL therapy the patients were prescribed between 1995 and
      2003/04 (including atypical NL other than clozapine) was considered. RESULTS: The
      prevalences found in 1995 and 2003/04 were 17% and 29% for Parkinsonism, 14% and
      14% for akathisia, and 24% and 13% for TD. There were considerable intra
      individual fluctuations in EPS occurrence even when the overall prevalence rate
      remained the same. In intra-individual comparisons of EPS ratings on both
      assessments, there was a tendency for worsening of Parkinsonism to be associated
      with a current (2003/04) therapy with typical NL; worsening of akathisia was
      associated with a current therapy with atypical NL other than clozapine,
      amelioration of akathisia with a current therapy with clozapine; and, basically,
      there were no significant associations found between the changes in TD ratings
      and the long-term therapy with typical NL, clozapine, and other atypical NL,
      considering cumulative doses of all these drugs. In a multivariate analysis,
      there was a tendency for the long-term evolution of TD to depend on illness
      duration as the only variable. CONCLUSIONS: There are intra-individual
      fluctuations in all EPS over longer time periods. The choice of current NL
      therapy has an impact on Parkinsonism and akathisia. The long-term evolution of
      TD appears independent of NL prescriptions.

PMID- 18055181
TI  - Genetic analysis of the gene coding for DARPP-32 (PPP1R1B) in Japanese patients
      with schizophrenia or bipolar disorder.
AB  - Several lines of evidence, including genome-wide linkage scans and postmortem
      brain studies of patients with schizophrenia or bipolar disorder, have suggested
      that DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa), a key
      regulatory molecule in the dopaminergic signaling pathway, is involved in these
      disorders. After evaluating the linkage disequilibrium pattern of the gene
      encoding DARPP-32 (PPP1R1B; located on 17q12), we conducted association analyses
      of this gene with schizophrenia and bipolar disorder. Single-marker and
      haplotypic analyses of four single nucleotide polymorphisms (SNPs; rs879606,
      rs12601930, rs907094, and rs3764352) in a sample set (subjects with
      schizophrenia=384, subjects with bipolar disorder=318, control subjects=384)
      showed that PPP1R1B polymorphisms were not significantly associated with
      schizophrenia, whereas, even after Bonferroni corrections, significant
      associations with bipolar disorder were observed for rs12601930 (corrected
      genotypic p=0.00059) and rs907094 (corrected allelic p=0.040). We, however, could
      not confirm these results in a second independent sample set (subjects with
      bipolar disorder=366, control subjects=370). We now believe that the significant
      association observed with the first sample set was a result of copy number
      aberrations in the region surrounding these SNPs. Our findings suggest that
      PPP1R1B SNPs are unlikely to be related to the development of schizophrenia and
      bipolar disorder in the Japanese population.

PMID- 18055182
TI  - Genetic transformation of the dermatophyte, Trichophyton mentagrophytes, based on
      the use of G418 resistance as a dominant selectable marker.
AB  - BACKGROUND: Dermatophytes are closely related keratinophilic fungal pathogens and
      are the causative agents of a superficial cutaneous infection called
      dermatophytosis (ringworm). A lack of gene manipulation techniques has prevented
      detailed analyses of the mechanisms of host invasion by dermatophytes. We have
      introduced the tetracycline-regulatable (TR) gene expression system into
      dermatophytes to facilitate functional analyses of genes essential for growth and
      virulence. As the TR gene expression system consists of two plasmid vector
      components, two dominant selectable markers are required for genetic
      transformation. In dermatophytes, only the hygromycin B phosphotransferase gene
      (hph) is available as a selectable marker. OBJECTIVE: We investigated the
      possibility of G418 resistance as a secondary selectable marker for genetic
      transformation in dermatophytes. METHODS: A series of plasmid vectors carrying
      the neomycin phosphotransferase gene (nptII) were introduced into the protoplasts
      of Trichophyton mentagrophytes, one of the most clinically important dermatophyte
      species, by polyethylene glycol (PEG)-mediated transformation. Transformants were
      selected on selective medium containing G418 at 300-500 microg/ml. RESULTS:
      Molecular biological analyses indicated that colonies appearing on the selective
      medium harbored nptII in their chromosomes. Colonies produced from protoplasts
      transformed with the enhanced green fluorescent protein (eGFP) gene-T.
      mentagrophytes cyclophilin cDNA (TmcypB) fusion vector also exhibited GFP
      fluorescence throughout their mycelia, but accumulation of the GFP-TmCYPB fusion
      protein in specific intracellular compartments was not observed. CONCLUSIONS:
      This study has provided a new selectable marker for genetic transformation in
      dermatophytes.

PMID- 18055183
TI  - Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic
      patients: intermittent versus continuous infusion.
AB  - Pharmacokinetics and pharmacodynamics are significantly altered in critically ill
      septic patients and the risk of prolonged periods with concentrations below the
      minimum inhibitory concentration (MIC) and of low area under the serum
      concentration-time curve/MIC (AUC/MIC) ratios is of concern. We compared the
      pharmacokinetic/pharmacodynamic (PK/PD) profile of linezolid administered by
      intermittent or continuous infusion in critically ill septic patients. Patients
      were divided into two groups: intermittent infusion (Group I) (600mg/12h); or
      continuous infusion (Group C) (300mg intravenous loading dose +900mg continuous
      infusion on Day 1, followed by 1200mg/daily from Day 2). Linezolid serum levels
      were monitored for 72h and microbiological data were collected. The clinical
      outcome was monitored. Sixteen patients completed the study. MICs of susceptible
      pathogens were 2mg/L for 80% of the isolates. In Group I, linezolid trough serum
      levels (C(min)) varied widely and were below the susceptibility breakpoint
      (4mg/L) during the study period; in 50% of patients C(min) was <1mg/L. In Group
      C, mean linezolid serum levels were more stable and, starting from 6h, were
      significantly higher than C(min) levels observed in Group I and were always above
      the susceptibility breakpoint. Time that the free drug concentration was above
      the MIC (T(free)>MIC) of>85% was more frequent in Group C than in Group I
      (P<0.05). Finally, with continuous infusion it was possible to achieve AUC/MIC
      values of 80-120 more frequently than with intermittent infusion (P<0.05).
      According to PK/PD parameters, continuous infusion has theoretical advantages
      over intermittent infusion in this population of patients.

PMID- 18055184
TI  - Brain response abnormalities during verbal learning among patients with
      schizophrenia.
AB  - Patients with schizophrenia often show verbal learning deficits that have been
      linked to the pathophysiology of the disorder and result in functional
      impairment. This study examined the biological basis of these deficits by
      comparing the brain response of patients with schizophrenia (n=17) to that of
      healthy comparison participants (n=14) during a verbal paired-associates learning
      task using functional magnetic resonance imaging (fMRI). Brain response during
      new word learning was examined within and between groups in two a priori regions
      of interest, the inferior frontal gyrus and hippocampus, and across the whole
      brain. In regions of group difference, we also examined the relationship of brain
      response during learning to later recall of the word pairs. Despite successful
      matching of levels of word-pair recall, patients' brain response during new
      learning was abnormal in bilateral regions within the inferior frontal gyrus, a
      small region in left posterior hippocampus, and other areas within the frontal,
      parietal and temporal cortex compared with healthy individuals. In some regions,
      but not in the hippocampus, patients with the most normal brain response also
      remembered the most word pairs following scanning. Thus, verbal learning deficits
      found among patients with schizophrenia appear to be related to hypofunction of
      distributed brain networks.

PMID- 18055185
TI  - Experimental determination of orientations for the 17 O electric-field-gradient
      and chemical shielding tensors in L-alanine.
AB  - We have presented a solid-state 17 O NMR study of [13C, 17 O]-L-alanine. Using
      the experimental results for the 13C-17 O dipolar vector and Euler angles, the
      absolute orientations of 17 O chemical shielding (CS) and electric-field-gradient
      (EFG) tensors with respect to the molecular frame can be determined for L
      alanine. The present results suggest that the intermediate EFG tensor components,
      VYY, lie in the carboxylate plane and parallel to the C-O bond directions, while
      the least shielded components, delta11, and the intermediate CS tensor
      components, delta22, roughly lie in the molecular plane and the direction of
      delta22 components are approximately 38 degrees and 25 degrees off the C-O bonds
      for O1 and O2, respectively. These results are in reasonable agreement with those
      of our quantum chemical calculations reported previously.

PMID- 18055186
TI  - Covalent immobilization of antibody fragments on well-defined polymer brushes via
      site-directed method.
AB  - Well-defined polymer brushes and block copolymer brushes consisting of 2
      methacryloyloxyethyl phosphorylcholine (MPC) and glycidyl methacrylate (GMA) were
      prepared by surface-initiated atom transfer radical polymerization (ATRP). The
      polymer brushes were used for the immobilization of antibody fragments in a
      defined orientation. Pyridyl disulfide moieties were introduced to the polymer
      brushes via a reaction of epoxy groups in GMA units. Fab' fragments were then
      immobilized onto these surfaces via a thiol-disulfide interchange reaction and
      the reactivity of antibodies with antigens was investigated. Antigen/antibody
      binding on the polymer brushes was more preferable than that on epoxysilane films
      as a control surface. Furthermore, the activity of the antibodies immobilized on
      the block copolymer brushes having biocompatible PMPC was greater than that on
      other surfaces that did not have PMPC in their structures.

PMID- 18055187
TI  - Binding and degradation of DNA on montmorillonite coated by hydroxyl aluminum
      species.
AB  - Adsorption, desorption and degradation by DNase I of DNA on montmorillonite (M)
      and different hydroxyaluminum-M complexes (Al(OH)(x)-M) containing 2.5, 10.0 and
      20.0 mmol coated Al/g clay (AM(2.5), AM(10) and AM(20)) were studied. The
      adsorption isotherms of DNA on montmorillonite and Al(OH)(x)-M complexes
      conformed to the Langmuir equation. The amount of DNA adsorbed followed the
      sequence of montmorillonite>AM(20)>AM(10)>AM(2.5). A marked decrease in the
      adsorption of DNA on montmorillonite and Al(OH)(x)-M complexes was observed with
      the increase of pH from 4.0 to 9.0. Calcium ion significantly promoted DNA
      adsorption. The adsorption enthalpy of DNA on montmorillonite was endothermic,
      whereas that on Al(OH)(x)-M complexes was exothermic. The percent desorption of
      DNA from clays was in the order of montmorillonite>AM(2.5)>AM(10)>AM(20),
      suggesting that OH-Al loading on montmorillonite surface increased the binding
      affinity of DNA. Fourier transform infrared (FTIR) spectra showed that the
      binding of DNA on AM(10) and AM(20) changed its conformation from the B-form to
      the Z-form. The presence of montmorillonite and Al(OH)(x)-M complexes provided
      protection for DNA against degradation by DNase I. The higher level of protection
      was found with Al(OH)(x)-M complexes compared to montmorillonite. The higher
      stability of DNA in the system of Al(OH)(x)-M complexes seemed to be attributed
      mainly to the conformational change of bound DNA and their greater adsorption
      capacity for DNase I. The information obtained in this study is of fundamental
      significance for understanding the behavior of extracellular DNA in soil
      environments.

PMID- 18055188
TI  - Characterization of the in vitro metabolic profile of amlodipine in rat using
      liquid chromatography-mass spectrometry.
AB  - In the present study, the metabolic profile of amlodipine, a well-known calcium
      channel blocker, was investigated employing liquid chromatography-mass
      spectrometric (LC/MS) techniques. Two different types of mass spectrometers - a
      triple-quadrupole (QqQ) and a quadrupole time-of-flight (Q-TOF) mass spectrometer
      - were utilized to acquire structural information on amlodipine metabolites. The
      metabolites were produced by incubation of amlodipine with primary cultures of
      rat hepatocytes. Incubations from rat hepatocytes were analyzed with LC-MS/MS,
      and 21 phase I and phase II metabolites were detected. Their product ion spectra
      were acquired and interpreted, and structures were proposed. Accurate mass
      measurement using LC-Q-TOF was used to determine the elemental composition of
      metabolites and thus to confirm the proposed structures of these metabolites.
      Mainly phase I metabolic changes were observed including dehydrogenation of the
      dihydropyridine core, as well as reactions of side chains, such as hydrolysis of
      ester bonds, hydroxylation, N-acetylation, oxidative deamination, and their
      combinations. The only phase II metabolite detected was the glucuronide of a
      dehydrogenated, deaminated metabolite of amlodipine. We propose several in vitro
      metabolic pathways of amlodipine in rat, based on our analysis of the metabolites
      detected and characterized.

PMID- 18055189
TI  - Hepatocellular toxicity of kava leaf and root extracts.
AB  - Kava extracts are used widely for different purposes and were thought to be safe.
      Recently, several cases of hepatotoxicity have been published. To explore
      possible mechanisms of kava hepatotoxicity, we prepared and analyzed three
      different kava extracts (a methanolic and an acetonic root and a methanolic leaf
      extract), and investigated their toxicity on HepG2 cells and isolated rat liver
      mitochondria. All three extracts showed cytotoxicity starting at a concentration
      of 50 microg/ml (lactate dehydrogenase leakage) or 1 microg/ml (MTT test). The
      mitochondrial membrane potential was decreased (root extracts starting at 50
      microg/ml) and the respiratory chain inhibited and uncoupled (root extracts) or
      only uncoupled (leaf extract) at 150 microg/ml, and mitochondrial beta-oxidation
      was inhibited by all extracts starting at 100 microg/ml. The ratio oxidized to
      reduced glutathione was increased in HepG2 cells, whereas the cellular ATP
      content was maintained. Induction of apoptosis was demonstrated by all extracts
      at a concentration of 150 microg/ml. These results indicate that the kava
      extracts are toxic to mitochondria, leading to inhibition of the respiratory
      chain, increased ROS production, a decrease in the mitochondrial membrane
      potential and eventually to apoptosis of exposed cells. In predisposed patients,
      mitochondrial toxicity of kava extract may explain hepatic adverse reactions of
      this drug.

PMID- 18055190
TI  - Pemphigoid gestationis autoantigen, transmembrane collagen XVII, promotes the
      migration of cytotrophoblastic cells of placenta and is a structural component of
      fetal membranes.
AB  - In pemphigoid gestationis (PG), autoantibodies target collagen XVII, a
      hemidesmosomal transmembrane protein, which is an important element in cutaneous
      epithelial adhesion and signalling. We report that collagen XVII is expressed in
      the first trimester and term syncytial and cytotrophoblastic cells of normal
      placenta and in epithelial cells of amniotic membrane. Immunoelectron microscopy
      confirmed the localization of collagen XVII to the hemidesmosomes of amniotic
      epithelium. Examination of three PG placentas showed mild villitis, but there
      were no differences between collagen XVII expression levels or immunostaining
      signals as compared to normal placenta. Collagen XVII expression was also
      detected in cultured extravillous trophoblast HTR-8/SVneo cells, where collagen
      XVII expression was upregulated by PMA and TGF-beta1. Interestingly, the presence
      of Col15, the cell migration domain of collagen XVII, induced the migration of
      HTR-8/SVneo cells in transmigration assay. Analysis of amniotic fluid samples at
      different gestational weeks revealed that a large quantity of collagen XVII
      ectodomain was shed into amniotic fluid throughout pregnancy. Biochemical and
      immunoblotting analysis indicated that the ectodomain in amniotic fluid is
      structurally very similar to the ectodomain produced by cultured keratinocytes.
      Cultured cells from amniotic fluid samples also expressed collagen XVII. Our
      results suggest that collagen XVII may contribute to the invasion of extravillous
      trophoblasts during placental development and is also required for the integrity
      of amniotic basement membrane. Although the exact pathomechanism of PG is still
      largely unknown, the clinical symptoms of PG are initiated after the expression
      of collagen XVII in placenta during the first trimester of pregnancy.

PMID- 18055191
TI  - Using exonuclease III to enhance electrochemical detection of natural DNA damage
      in layered films.
AB  - The natural double-stranded DNA (dsDNA) was immobilized on electrode surface by
      layer-by-layer assembly, forming PSS/PDDA/dsDNA films (PSS, poly(styrene
      sulfonate); PDDA, poly(diallyldimethylammonium)), and used to detect DNA damage
      electrochemically. The DNA lesion induced by the alkylating agent methyl
      methanesulfonate (MMS) could be detected by cyclic voltammetry with ruthenium(II)
      tris(2,2'-bipyridyl) (Ru(bpy)(3)(2+)) in solution. After treated by E. coli
      exonuclease III enzyme, the electrocatalytic oxidation peak of the films was
      further amplified and greatly enhanced because the enzyme could convert those
      apurinic sites caused by MMS in the damaged dsDNA into single-stranded DNA
      regions and make more guanines in the DNA become exposed. This approach provided
      a novel idea for constructing DNA biosensor in sensitive screening of genetoxic
      chemicals in vitro.

PMID- 18055192
TI  - Development of a mast cell-based biosensor.
AB  - A mast cell-based biosensor has been developed to enable the use of these cells
      in numerous applications including pharmaceutical screening, environmental
      monitoring, clinical diagnosis and homeland security. Rat basophilic leukemia
      (RBL) mast cells offer excellent potential for biosensor applications because
      they are robust and undergo a dramatic exocytotic response within minutes of
      antigen addition. To monitor mast cell activation, fluorescent dyes were loaded
      into the cells and used as indicators of alkalinization of secretory granules,
      calcium fluxes or generation of reactive oxygen species. These fluorescence
      assays efficiently measure activation of antigen-stimulated RBL mast cells,
      detecting the antigen with picomolar sensitivity. To demonstrate the utility of
      this mast cell-based biosensor for detection of microbial pathogens, an IgE
      chimeric protein was created by fusing the Fc region of the IgE antibody to CD14,
      a receptor for lipopolysaccharide. This chimeric protein has the capacity to bind
      to Escherichia coli and Listeria monocytogenes and also to IgE receptors on the
      mast cells, thereby stimulating a signaling response to bacteria. RBL mast cells
      labeled with the calcium indicator Fluo-4 are shown to be responsive to E. coli,
      only when sensitized with the chimeric protein, thus demonstrating a highly
      versatile biosensor for bacterial contamination.

PMID- 18055193
TI  - Metabolic syndrome and cancer risk.
AB  - OBJECTIVE: The purpose of this population-based study is to explore for the first
      time the link between metabolic syndrome and cancer risk using information from
      the health information system of the Cancer Registry. METHODS: Referring to all
      pharmaceutical prescriptions between 1 January 1999 and 31 December 2005, coded
      with the Anatomical Therapeutic Chemical classification, all subjects aged 40 and
      over resident in Milan, which were simultaneously prescribed with
      antihypertensive, hypolypemic and hypoglycaemic drugs, were considered affected
      by metabolic syndrome. New cancer cases among cohort subjects were identified
      trough the local Cancer Registry and standardised incidence ratios (and
      corresponding 95% exact confidence intervals) were computed. RESULTS: Overall
      16,677 subjects were identified corresponding to 45,828 person-years; among them
      823 incidents cancers occurred. Significantly increased risks for pancreatic
      cancer in males--SIR 178 (114-266)--and colorectal cancer in females--SIR 133
      (101-170)--were observed. Non-significantly increased risks were also observed in
      women for liver, gallbladder and biliary tract, breast and endometrial cancers.
      CONCLUSIONS: Our study suggests that the risk for several cancers increases in
      subjects affected by metabolic syndrome. The pharmacological control of the
      syndrome seems to be inadequate for reducing cancer risk, even though both a high
      competitive mortality effect and short duration of follow up have to be
      considered.

PMID- 18055194
TI  - Risk factors in germ cell tumour patients with relapse or progressive disease
      after first-line chemotherapy: evaluation of a prognostic score for survival
      after high-dose chemotherapy.
AB  - PURPOSE: To retrospectively re-evaluate a published prognostic score for response
      to salvage treatment in patients with germ-cell tumours relapsing or progressing
      after cisplatin-based first-line chemotherapy. PATIENTS AND METHODS: From a
      database of 257 germ cell tumour (GCT) patients treated with salvage high-dose
      chemotherapy (HDCT) we identified 176 patients (67%) with relapse or progression
      after first-line conventional-dose chemotherapy (CDCT). Patients were
      retrospectively grouped according to a published prognostic score defined by
      Fossa and colleagues [Fossa SD, Stenning SP, Gerl A, et al. Prognostic factors in
      patients progressing after cisplatin-based chemotherapy for malignant non
      seminomatous germ cell tumors. Br J Cancer 1999; 80:1392-9]. Overall survival
      (OS) and event free survival (EFS) after HDCT were retrospectively evaluated in
      each prognostic group. RESULTS: After a median follow-up of 9 years the OS
      probability for all 176 patients was 38% and the EFS probability was 35%. The
      respective survival probability at 5 years in 100/176 (57%) good prognosis
      patients and 76/176 (43%) poor prognosis patients were 47% versus 28% for OS
      (p<0.001) and 41% versus 26% for EFS (p<0.005). Whereas survival probabilities
      did not differ in good prognosis patients, OS and EFS in poor prognosis patients
      were substantially better in the current series of patients treated with HDCT
      compared to the ones reported by Fossa treated with CDCT. CONCLUSION: This
      retrospective analysis confirms the impact of prognostic factors on the results
      of salvage treatment in patients with GCT and suggests a clinical benefit for
      patients with poor prognosis features receiving a single course of HDCT.

PMID- 18055195
TI  - Stool test for colorectal cancer screening: what is going on?
AB  - Given the increasing incidence of colorectal cancer (CRC), performing new and
      cost-effective stool tests is of particular importance for early diagnosis and
      treatment. In the present review, we describe the main characteristics, and the
      performance of the most recently developed stool tests in the screening setting
      of colorectal tumoral diseases. Most of the studies reported high sensitivity
      both for adenomas and CRC diagnosis; less than half studies reported also high
      specificity with respect to stage and localization of the tumor. However, the
      performance of every single test was extremely variable, reaching >95%
      specificity for most of DNA-based markers, although lacking sensitivity even in
      case of invasive CRC. A new potential stool marker of colon cancer is clusterin,
      a protein of particular interest for its high sensitivity and positive predictive
      value in patients with highly aggressive CRC.

PMID- 18055196
TI  - Cryosurgical ablation of hepatic colorectal metastases.
AB  - Hepatic resection is the treatment of choice for primary and secondary hepatic
      tumors but only 15-25% of patients with hepatic colorectal metastases are
      eligible for a curative hepatic resection. Cryosurgical ablation (CSA) is
      employed when curative resection of metastases cannot be obtained. Sixty-four
      patients (35 males, 29 females, mean age 58.8 years, range 30-79 years) with
      hepatic colorectal metastases underwent CSA, under laparoscopic control (15
      cases) or with open surgery (49 cases), with subsequent close follow-up.
      Intraoperative bleeding occurred in 32 out of 49 patients in the open group and
      only in 2 patients in the laparoscopic group. Minor morbidity that resolved with
      conservative treatment was 54.8% in the open group and 53.3% in the laparoscopic
      group. Major morbidity occurred in 11 cases (26.2%) in the open group and in 1
      case (6.7%) in the laparoscopic group. Mortality occurred in two patients, both
      in the open group, from renal insufficiency in one case and from liver failure in
      the other case. Mean hospital stay was 16.7 days in the open group (range 8-72
      days) and 10.6 days in the laparoscopic group (range 3-18 days). No patient was
      lost to follow-up. At a mean follow-up of 87.1 months (range 52.2-125.2 months),
      selected patients undergoing laparoscopic CSA had an overall survival rate of
      66.7% (10 patients), with 30% of patients (3) who are disease-free. Median
      survival was 94.2 months. Recurrence was observed in seven patients. None of the
      intrahepatic recurrences was at the cryoablation site. In the open group, median
      survival was 22.9 months with a survival rate of 30.9% (13 patients) at a mean
      follow-up of 39.3 months (range 1.9-124.5 months); 9 patients (19.1%) are disease
      free. In selected patients, laparoscopic CSA is associated with survival rates
      which are similar to those after hepatic resection. In patients with a larger
      tumor burden, CSA offers a curative treatment to patients with otherwise a dismal
      prognosis and it improves survival as compared to patients receiving chemotherapy
      alone. However, the procedure is associated with substantial morbidity,
      particularly bleeding, and therefore careful patient selection is recommended.

PMID- 18055197
TI  - Investigation of the sorption mechanisms of metal-complexed dye onto Posidonia
      oceanica (L.) fibres through kinetic modelling analysis.
AB  - This research deals with the exploitation of highly available and renewable
      marine biomass, Posidonia oceanica (L.) fibres as low cost biosorbent for the
      removal of metal-complexed textile dyestuff from aqueous medium, and the
      investigation of the probably involved physiochemical mechanisms. Experiments
      were carried out in batch reactor. Firstly, the adsorption process was studied as
      a function of initial solution pH and contact time under different initial dye
      concentration. The results showed that the highest dye adsorption capacity was
      found at pH 2 under a constant temperature of 30 degrees C, and the equilibrium
      state was reached within 48 h of exposure time. Secondly, several adsorption
      kinetic models were applied to fit the experimental data, namely Lagergren
      irreversible first-order, Reversible first-order, Pseudo-second-order, Elovich,
      Ritchie and intraparticle diffusion models. The proposed explanations were
      deduced from the theoretical assumptions behind the most appropriate model(s),
      which could satisfactorily describe the present biosorption phenomenon. The
      interpretation of the related results have shown that, with R(2) of about 99%,
      the pseudo-second order model is the most suitable dynamic theory describing the
      biosorption of metal complex dye onto P. oceanica fibres, predicting therefore a
      chemisorption process.

PMID- 18055198
TI  - Parameter and process significance in mechanistic modeling of cellulose
      hydrolysis.
AB  - A process-based model relevant to landfill and anaerobic digesters was developed,
      which included a novel approach to biomass transfer between a cellulose-bound
      biofilm and biomass in the bulk liquid. Model results highlighted the
      significance of the bacterial colonization of cellulose particles by attachment
      through contact in solution. Simulations revealed that both enhanced colonization
      and cellulose degradation are associated with reduced cellulose particle size,
      increased biomass populations in solution and increased cellulose-binding ability
      of the biomass. This suggests that transportation of biomass into the system from
      elsewhere and/or bacterial inoculation of such systems could enhance degradation
      significantly. A sensitivity analysis of the system parameters revealed the
      biological rate and yield properties of the hydrolyzing bacteria are most
      significant with regard to cellulose degradation in the system.

PMID- 18055199
TI  - Eco-friendly and efficient one-pot synthesis of alkyl- or aryl-14H
      dibenzo[a,j]xanthenes in water.
AB  - Alkyl- or aryl-14H-dibenzo[a,j]xanthene derivatives are synthesized efficiently
      by the reaction of beta-naphthol and aliphatic and aromatic aldehydes in the
      presence of KAl(SO4)2 x 12 H2O (alum) under aqueous condition at 100 degrees C.
      Different types of aromatic and aliphatic aldehydes are used in the reaction and
      in all cases the products synthesized successfully. Several solvents were
      examined for this reaction; however, in terms of reaction yield and time, water
      was found to be the optimum solvent.

PMID- 18055200
TI  - A method for the synthesis of an oseltamivir PET tracer.
AB  - A protocol applicable for the synthesis of an oseltamivir positron emission
      tomography (PET) tracer was developed. Acetylation of amine 3 with CH(3)COCl,
      followed by deprotection and aqueous workup, produced oseltamivir 4 from 3 within
      10 min. The obtained 4 was sufficiently pure for PET studies. This method can be
      extended to PET tracer synthesis using CH(3)(11)COCl.

PMID- 18055201
TI  - Preparation of C60-based active esters and coupling of C60 moiety to amines or
      alcohols.
AB  - We report the syntheses of C(60)-based active esters and the coupling of their
      C(60) moiety to various amines or alcohols. Methano[60]fullerene carboxylic acid
      was activated by esterification with N-hydroxysuccinimide (NHS) or
      pentafluorophenol (PFP) and the active esters were isolated. Reactions of the
      active esters with amines or alcohols proceeded easily to give a variety of
      compounds having the C(60) moiety.

PMID- 18055202
TI  - (Phenylpiperazinyl)cyclohexylureas: discovery of alpha1a/1d-selective adrenergic
      receptor antagonists for the treatment of benign prostatic hyperplasia/lower
      urinary tract symptoms (BPH/LUTS).
AB  - Benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) can be
      effectively treated with alpha(1) adrenergic receptor antagonists. Unfortunately,
      currently marketed alpha(1) blockers produce CV-related side effects that are
      caused by the subtype non-selective nature of the drugs. To overcome this
      problem, it was postulated that an alpha(1a/1d) subtype-selective antagonist
      would bring more benefit for the treatment of BPH/LUTS. As a continuation of our
      effort to develop selective alpha(1a/1d) ligands, a series of
      (phenylpiperazinyl)cyclohexylureas was synthesized and evaluated for the ability
      to bind to three cloned human alpha(1)-adrenergic receptor subtypes. Several
      trans isomers were shown to have equal affinity for both alpha(1a), and alpha(1d)
      subtypes, with 14- to 47-fold selectivity versus the alpha(1b) subtype and >15
      fold selectivity versus dopamine D(2).

PMID- 18055203
TI  - Identification of 2-amino-5-(thioaryl)thiazoles as inhibitors of nerve growth
      factor receptor TrkA.
AB  - 2-Amino-5-(thioaryl)thiazoles are potent inhibitors of TrkA (e.g., 20h, TrkA
      IC(50)=0.6 nM) that show anti-proliferative effect in cellular assays. A proposed
      inhibitor binding mode to TrkA active site is consistent with key SAR
      observations.

PMID- 18055204
TI  - Potency and selectivity of P2/P3-modified inhibitors of cysteine proteases from
      trypanosomes.
AB  - A systematic study of P2 and P3 substitution in a series of vinyl sulfone
      cysteine protease inhibitors is described. The introduction of a methyl
      substituent in the P2 phenylalanine aryl ring had a favorable effect on protease
      inhibition and conferred modest selectivity for rhodesain over cruzain. Rhodesain
      selectivity could be enhanced further by combining these P2 modifications with
      certain P3 amide substituents.

PMID- 18055205
TI  - Block of cyclic nucleotide-gated channels by tetracaine derivatives: role of
      apolar interactions at two distinct locations.
AB  - A series of new tetracaine derivatives was synthesized to explore the effects of
      hydrophobic character on blockade of cyclic nucleotide-gated (CNG) channels.
      Increasing the hydrophobicity at either of two positions on the tetracaine
      scaffold, the tertiary amine or the butyl tail, yields blockers with increased
      potency. However, shape also plays an important role. While gradual increases in
      length of the butyl tail lead to increased potency, substitution of the butyl
      tail with branched alkyl or cyclic groups is deleterious.

PMID- 18055206
TI  - Structure-based design and synthesis of novel macrocyclic pyrazolo[1,5-a]
      [1,3,5]triazine compounds as potent inhibitors of protein kinase CK2 and their
      anticancer activities.
AB  - A series of macrocyclic derivatives has been designed and synthesized based on
      the X-ray co-crystal structures of pyrazolo[1,5-a] [1,3,5]triazines with corn CK2
      (cCK2) protein. Bioassays demonstrated that these macrocyclic pyrazolo[1,5-a]
      [1,3,5]triazine compounds are potent CK2 inhibitors with K(i) around 1.0 nM and
      strongly inhibit cancer cell growth with IC(50) as low as approximately 100 nM.

PMID- 18055207
TI  - Bone union of painful bipartite patella after treatment with low-intensity pulsed
      ultrasound: report of two cases.
AB  - We report two cases of painful bipartite patella in which bone union was achieved
      after treatment with low-intensity pulsed ultrasound. Both patients were 13-year
      old males. Each received ultrasound (SAFHS, EXOGEN) for 20 min a day. The
      interval between the onset of pain and ultrasound treatment was between 2 and 4
      months. The patellar pain disappeared within two months after treatment in both
      cases. Bone union was seen radiographically at 4 months. Low-intensity pulsed
      ultrasound is a non-invasive treatment that appeared to be helpful in the
      management of two patients with painful bipartite patella.

PMID- 18055208
TI  - Biomimetic synthesis of xuxuarines Ealpha and Ebeta: structure revision of
      Rzedowskia bistriterpenoids.
AB  - Reaction of pristimerin with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)
      resulted in a biomimetic-type coupling leading to xuxuarines Ealpha and Ebeta and
      not the previously reported Rzedowskia bistriterpenoids I and II suggesting that
      the structures proposed for these natural products need revision. A product
      obtained in this reaction by an unusual Diels-Alder addition followed by retro
      Diels-Alder-type elimination was characterized as pristimerin
      dicyanophenalenedione. Complete 1H, and 13C NMR spectral assignments of
      xuxuarines Ealpha and Ebeta have been made by the application of 1D and 2D NMR
      techniques.

PMID- 18055210
TI  - The use of dendritic cells in cancer immunotherapy.
AB  - Cancer immunotherapy aims at eliciting an immune response directed against tumor
      antigens to help fight off residual tumor cells and thereby improve survival and
      quality of life of cancer patients. Different immunotherapeutic approaches share
      the use of dendritic cells (DCs) to present tumor-associated antigens to T
      lymphocytes. Ex vivo generated DCs can be loaded with antigens and re-infused to
      the patients, or they can be used for ex vivo expansion of antitumor lymphocytes.
      Alternatively, methods exist to target antigens to DCs in vivo without need for
      ex vivo cell manipulations. The clinical studies have shown that DC
      administration to patients is safe and induces antigen-specific immunity.
      However, it seldom elicits objective clinical responses in patients with advanced
      stage malignancies. Novel insights into DC and lymphocyte regulation are expected
      to lead to more effective vaccines in the near future. Meanwhile, efforts are
      directed at identifying the most appropriate clinical targets for active specific
      immunotherapies. Data suggests that vaccinations may indeed be beneficial when
      given in the adjuvant setting rather than to treat metastatic cancers. These
      issues are discussed here together with an overview of the DC-based antitumor
      immunotherapy studies.

PMID- 18055209
TI  - CD40L disruption enhances Abeta vaccine-mediated reduction of cerebral
      amyloidosis while minimizing cerebral amyloid angiopathy and inflammation.
AB  - Amyloid-beta (Abeta) immunization efficiently reduces amyloid plaque load and
      memory impairment in transgenic mouse models of Alzheimer's disease (AD). Active
      Abeta immunization has also yielded favorable results in a subset of AD patients.
      However, a small percentage of patients developed severe aseptic
      meningoencephalitis associated with brain inflammation and infiltration of T
      cells. We have shown that blocking the CD40-CD40 ligand (L) interaction mitigates
      Abeta-induced inflammatory responses and enhances Abeta clearance. Here, we
      utilized genetic and pharmacologic approaches to test whether CD40-CD40L blockade
      could enhance the efficacy of Abeta(1-42) immunization, while limiting
      potentially damaging inflammatory responses. We show that genetic or
      pharmacologic interruption of the CD40-CD40L interaction enhanced Abeta(1-42)
      immunization efficacy to reduce cerebral amyloidosis in the PSAPP and Tg2576
      mouse models of AD. Potentially deleterious pro-inflammatory immune responses,
      cerebral amyloid angiopathy (CAA) and cerebral microhemorrhage were reduced or
      absent in these combined approaches. Pharmacologic blockade of CD40L decreased T
      cell neurotoxicity to Abeta-producing neurons. Further reduction of cerebral
      amyloidosis in Abeta-immunized PSAPP mice completely deficient for CD40 occurred
      in the absence of Abeta immunoglobulin G (IgG) antibodies or efflux of Abeta from
      brain to blood, but was rather correlated with anti-inflammatory cytokine
      profiles and reduced plasma soluble CD40L. These results suggest CD40-CD40L
      blockade promotes anti-inflammatory cellular immune responses, likely resulting
      in promotion of microglial phagocytic activity and Abeta clearance without
      generation of neurotoxic Abeta-reactive T-cells. Thus, combined approaches of
      Abeta immunotherapy and CD40-CD40L blockade may provide for a safer and more
      effective Abeta vaccine.

PMID- 18055211
TI  - Electron detachment dissociation of dermatan sulfate oligosaccharides.
AB  - The structural characterization of glycosaminoglycans (GAG) oligosaccharides has
      been a long-standing challenge in the field of mass spectrometry. In this work,
      we present the application of electron detachment dissociation (EDD) Fourier
      transform mass spectrometry to the analysis of dermatan sulfate (DS)
      oligosaccharides up to 10 residues long. The EDD mass spectra of DS
      oligosaccharides were compared with their infrared multiphoton dissociation
      (IRMPD) mass spectra. EDD produces more abundant fragmentation than IRMPD with
      far less loss of SO3 from labile sulfate modifications. EDD cleaves all
      glycosidic bonds, yielding both conventional glycosidic bond fragmentation as
      well as satellite peaks resulting from the additional loss of 1 or 2 hydrogen
      atoms. EDD also yields more cross-ring fragmentation than IRMPD. For EDD,
      abundant cross-ring fragmentation in the form of A- and X-ions is observed, with
      1,5Xn cleavages occurring for all IdoA residues and many of the GalNAc4S
      residues, except at the reducing and nonreducing ends. In contrast, IRMPD
      produces only A-type cross-ring fragmentation for long oligosaccharides (dp6
      dp10). As all the structurally informative fragment ions observed by IRMPD appear
      as a subset of the peaks found in the EDD mass spectrum, EDD shows great
      potential for the characterization of GAG oligosaccharides using a single tandem
      mass spectrometry experiment.

PMID- 18055212
TI  - Detection of ATP-binding to growth factors.
AB  - It was shown in previous work that the interaction of growth factors (GFs) with
      adenosine triphosphate (ATP) is essential for their neuroprotective effect. Here
      we investigated the nature of the association of human basic fibroblast growth
      factor (bFGF), nerve growth factor (NGF), and brain-derived neurotrophic factor
      (BDNF) with ATP. It was demonstrated that this interaction involves the formation
      of non-covalent ATP-GF complexes that are labile at low pH and that could be
      selectively purified and subjected to electrospray and MALDI-TOF mass
      spectrometry. The results obtained with these techniques indicated that the
      stability of the complexes is high. Main features of the procedure used here are:
      (1) reversed-phase purification of nucleotide-protein non-covalent complexes, (2)
      their detection with MALDI-TOF-MS using acid-free matrix, and/or (3) their
      measurement with ESI-MS using soft desolvation conditions. The methodology was
      successful in providing proof for the presence of various nucleotide-GF
      complexes. It was extended to other nucleotide-binding proteins (ribonuclease A)
      as well as proteins that do not exhibit nucleotide binding (lysozyme) as positive
      and negative control, respectively. Thus, the method demonstrated its general use
      for the investigation of a wide range of proteins interacting with nucleotides as
      long as their complexes are sufficiently stable to accommodate the experimental
      conditions.

PMID- 18055213
TI  - Actin is where it's at.

PMID- 18055214
TI  - Palmitoylation of the C-terminal fragment of p75(NTR) regulates death signaling
      and is required for subsequent cleavage by gamma-secretase.
AB  - It has recently been shown that the p75 neurotrophin receptor (p75(NTR)), which
      is known to mediate neural cell death during development of the nervous system
      and in a range of adult neurodegenerative conditions, undergoes a regulated
      process of cell surface receptor cleavage, regulated intramembrane proteolysis
      (RIP). Here we show that neuronal death signaling occurs only following
      extracellular metalloprotease cleavage of p75(NTR) and palmitoylation of the
      resultant C-terminal fragment, causing its translocation to cholesterol-rich
      domains of the plasma membrane. Furthermore, death signaling is promoted by
      inhibition of intracellular gamma-secretase cleavage, a process which also occurs
      within the cholesterol-rich domains. In the presence of TrkA signaling, C
      terminal fragment localization in these cholesterol-rich domains is prevented,
      thereby blocking neuronal death. Thus p75(NTR) activates neuronal death pathways
      in conditions where the balance of normal RIP is shifted toward extracellular
      domain cleavage due to increased metalloprotease activity, decreased TrkA
      activity or compromised gamma-secretase activity, all of which are features of
      neurodegenerative conditions such as Alzheimer's disease.

PMID- 18055216
TI  - How has DISC1 enabled drug discovery?
AB  - Growing genetic and clinical evidence has shown that disrupted-in-schizophrenia 1
      (DISC1) is one of the most compelling risk genes for schizophrenia and other
      major mental disorders. The understanding of the role that DISC1 plays in
      neuronal development and cell signaling has been greatly enhanced by the
      identification of DISC1 binding partners, an appreciation of its expression
      during development and functional studies using RNA interference. But what is the
      impact of this explosion of data for psychiatric drug discovery? Though we are at
      a very early stage of our understanding of DISC1 biology, it is an important time
      to review what has already been achieved and to discuss its impact. DISC1 biology
      has enabled the identification of new therapeutic targets in the form of DISC1
      binding partners and other molecules found within a large DISC1 interaction
      network, the so-called 'DISC1 interactome'. We will review the better
      characterized of these interactions and also emphasize the richness of potential
      targets in the more poorly studied areas of the interactome. Furthermore, DISC1
      has encouraged the development of new animal models for psychiatric disorders,
      which is critical for the study of disease biology. Thus, DISC1 may have the
      potential to not only point us in the direction of novel drug targets but also
      provide more relevant animal models for compound testing.

PMID- 18055215
TI  - Membrane depolarization inhibits spiral ganglion neurite growth via activation of
      multiple types of voltage sensitive calcium channels and calpain.
AB  - The effect of membrane electrical activity on spiral ganglion neuron (SGN)
      neurite growth remains unknown despite its relevance to cochlear implant
      technology. We demonstrate that membrane depolarization delays the initial
      formation and inhibits the subsequent extension of cultured SGN neurites. This
      inhibition depends directly on the level of depolarization with higher levels of
      depolarization causing retraction of existing neurites. Cultured SGNs express
      subunits for L-type, N-type, and P/Q type voltage-gated calcium channels (VGCCs)
      and removal of extracellular Ca(2+) or treatment with a combination of L-type, N
      type, and P/Q-type VGCC antagonists rescues SGN neurite growth under depolarizing
      conditions. By measuring the fluorescence intensity of SGNs loaded with the
      fluorogenic calpain substrate t-butoxy carbonyl-Leu-Met-chloromethylaminocoumarin
      (20 microM), we demonstrate that depolarization activates calpains. Calpeptin (15
      microM), a calpain inhibitor, prevents calpain activation by depolarization and
      rescues neurite growth in depolarized SGNs suggesting that calpain activation
      contributes to the inhibition of neurite growth by depolarization.

PMID- 18055217
TI  - SOCS3 suppresses AP-1 transcriptional activity in neuroblastoma cells through
      inhibition of c-Jun N-terminal kinase.
AB  - Transduction and activation of an inducible form of STAT3 (signal transducer and
      activator of transcription) sufficed to increase VIP (vasoactive intestinal
      protein) mRNA concentrations in neuroblastoma cells. Overexpression of SOCS3
      (suppressor of cytokine signaling) inhibited and mutant SOCS3 (with an
      inactivating point mutation in amino acid 25) enhanced the induction of VIP mRNA
      by CNTF (ciliary neurotrophic factor). Because mutant SOCS3 did not augment the
      increase in STAT transcriptional activity following CNTF stimulation, the
      enhancement by mutant SOCS3 of the actions of CNTF cannot be attributed to
      changes in STAT3 signaling. Mutant SOCS3 increased AP-1 (activator protein)
      transcriptional activity and JNK (c-Jun N-terminal kinase) activity and SOCS3
      bound to the scaffolding protein, JNK-interacting protein-1: these observations
      provide a plausible explanation for the enhancement by mutant SOCS3 of the
      actions of CNTF. We conclude that endogenous SOCS3 inhibits AP-1 activity through
      blocking of JNK phosphorylation.

PMID- 18055218
TI  - GABAergic drugs become neurotoxic in cortical neurons pre-exposed to brain
      derived neurotrophic factor.
AB  - A 24-h pretreatment with BNDF enhanced excitotoxic neuronal death in cultured
      mouse cortical cells challenged with NMDA in the presence of extracellular
      Mg(2+). The GABA(A) receptor antagonist, bicuculline, enhanced NMDA toxicity in
      control cultures but, unexpectedly, became neuroprotective in cultures pretreated
      with BDNF. In contrast, drugs that activate GABA(A) receptors (e.g. muscimol,
      benzodiazepines, or phenobarbital) or drugs that indirectly enhance GABAergic
      transmission were protective in control cultures but amplified NMDA toxicity
      after pretreatment with BDNF. The atypical behaviour of GABAergic drugs in
      cultures pretreated with BDNF depended on changes in the anion reversal potential
      because (i) increases in extracellular Cl(-) concentrations abolished the
      neurotoxic action of muscimol; (ii) muscimol stimulated (36)Cl(-) efflux after
      pretreatment with BDNF; and (iii) exposure to BDNF reduced the expression of the
      neuronal K(+)/Cl(-) co-transporter, KCC2. Our data raise the concern that
      GABAergic drugs may become neurotoxic under conditions associated with increases
      in brain BDNF levels.

PMID- 18055219
TI  - A simple two step procedure for purification of the catalytic domain of chicken
      tryptophan hydroxylase 1 in a form suitable for crystallization.
AB  - Tryptophan hydroxylase (TPH) [EC 1.14.16.4] catalyzes the conversion of
      tryptophan to 5-hydroxytryptophan, which is the first and rate-determining step
      in the biosynthesis of the neurotransmitter serotonin. We have expressed the
      catalytic domain of chicken (Gallus gallus) TPH isoform 1 in Escherichia coli in
      high yield. The enzyme was highly purified using only one anion exchange and one
      gel filtration, with a yield of 11 mg/L culture and a specific activity of 0.60
      micromol/min/mg. The K(m) values were determined to K(m, tryptophan)=7.7+/-0.7
      microM, K(m, BH4)=324+/-10 microM and K(m, O2)=39+/-2 microM. Substrate
      inhibition by tryptophan was observed at concentrations above 15 microM.
      Furthermore, the purified enzyme has been crystallized without 7,8-dihydro-L
      biopterin and a data set to 3A resolution has been collected.

PMID- 18055220
TI  - The effect of an on-body personal lift assist device (PLAD) on fatigue during a
      repetitive lifting task.
AB  - Occupations demanding frequent and heavy lifting are associated with an increased
      risk of injury. A personal lift assist device (PLAD) was designed to assist human
      muscles through the use of elastic elements. This study was designed to determine
      if the PLAD could reduce the level of general and local back muscle fatigue
      during a cyclical lifting task. Electromyography of two erector spinae sites (T9
      and L3) was recorded during a 45-min lifting session at six lifts/lowers per
      minute in which male participants (n=10) lifted a box scaled to represent 20% of
      their maximum back extensor strength. The PLAD device reduced the severity of
      muscular fatigue at both muscle sites. RMS amplitude increased minimally (22% and
      26%) compared to the no-PLAD condition (104% and 88%). Minimal median frequency
      decreases (0.33% and 0.41%) were observed in the PLAD condition compared to drops
      of 12% and 20% in the no-PLAD condition. The PLAD had an additional benefit of
      minimizing pre-post changes in muscular strength and endurance. The PLAD also
      resulted in a significantly lower rate of perceived exertion across the lifting
      session. It was concluded that the PLAD was effective at decreasing the level of
      back muscular fatigue.

PMID- 18055221
TI  - The interpretation of abdominal wall muscle recruitment strategies change when
      the electrocardiogram (ECG) is removed from the electromyogram (EMG).
AB  - The purpose of this study was to determine the effect of the ECG artifact on low
      level trunk muscle activation amplitudes and assess the effectiveness of two
      methods used to remove the ECG. Simulations were performed and percent error in
      root mean square (RMS) amplitudes were calculated from uncontaminated and
      contaminated EMG signals at various ECG to EMG ratios. Two methods were used to
      remove the ECG: (1) filtering by adaptive sampling (FAS) and (2) Butterworth high
      pass filter at 30 Hz (BW-30 Hz HPF). The percent error was also calculated
      between the ECG removed and the uncontaminated EMG RMS amplitudes. Next, the BW
      30 Hz HPF method was used to remove the ECG from 3-bilateral external oblique
      (EO) muscle sites collected from 30 healthy subjects performing a one handed lift
      and replace task. Two separate ANOVA models assessed the effects of ECG on the
      statistical interpretation of EO recruitment strategies. One model included EMG
      data that contained the ECG and the other model included EMG data after the ECG
      was removed. Large percent errors were observed when the ECG was not removed.
      These errors increased with larger ECG to EMG ratios. Both removal methods
      reduced the errors to below 10%, but the BW-30 Hz HPF method was more time
      efficient in removing the ECG artifact. Different statistical findings were
      observed among the muscle sites for the ECG contaminated model compared to the
      ECG removed model, which resulted in different conclusions concerning
      neuromuscular control.

PMID- 18055223
TI  - Does physical interstimulus variance account for early electrophysiological face
      sensitive responses in the human brain? Ten lessons on the N170.
AB  - A recent event-related potential (ERP) study (Thierry G., Martin, C.D., Downing,
      P., Pegna, A.J. 2007. Controlling for interstimulus perceptual variance abolishes
      N170 face selectivity. Nature Neuroscience, 10, 505-11) claimed that the larger
      occipito-temporal N170 response to pictures of faces than other categories -- the
      N170 effect -- is due to a methodological artifact in stimulus selection,
      specifically, a greater interstimulus physical variance between pictures of
      objects than faces in previous ERP studies which, when controlled, eliminates
      this N170 effect. This statement casts doubts on the validity of the conclusions
      reached by a whole tradition of electrophysiological experiments published over
      the past 15 years and questions the very interest of using the N170 to probe the
      time course of face processes in the human brain. Here we claim that this
      physical variance factor is ill-defined by Thierry et al. and cannot account for
      previous observations of a smaller N170 amplitude to nonface objects than faces
      without latency increase and component "smearing". Most importantly, this factor
      was controlled in previous studies that reported robust N170 effects. We
      demonstrate that the absence of N170 effect in the study of Thierry et al. is due
      to methodological flaws in the reported experiments, most notably measuring the
      N170 at the wrong electrode sites. Moreover, the authors attributed a modulation
      of N170 amplitude in their study to a differential interstimulus physical
      variance while it probably reflects a biased comparison of different quality sets
      of individual images. Here, by taking Thierry et al.'s study as an exemplar case
      of what should not be done in ERP research of visual categorization processes, we
      provide clarifications on a number of methodological and theoretical issues about
      the N170 and its largest amplitude to faces. More generally, we discuss the
      potential role of differential visual homogeneity of object categories as well as
      low-level visual properties versus high-level visual processes in accounting for
      early face-preferential responses and the question of the speed at which visual
      stimuli are categorized as faces. This survey of the literature points to the
      N170 as a critical event in the time course of face processes in the human brain.

PMID- 18055222
TI  - Accurate prediction of V1 location from cortical folds in a surface coordinate
      system.
AB  - Previous studies demonstrated substantial variability of the location of primary
      visual cortex (V1) in stereotaxic coordinates when linear volume-based
      registration is used to match volumetric image intensities [Amunts, K.,
      Malikovic, A., Mohlberg, H., Schormann, T., and Zilles, K. (2000). Brodmann's
      areas 17 and 18 brought into stereotaxic space-where and how variable?
      Neuroimage, 11(1):66-84]. However, other qualitative reports of V1 location
      [Smith, G. (1904). The morphology of the occipital region of the cerebral
      hemisphere in man and the apes. Anatomischer Anzeiger, 24:436-451; Stensaas,
      S.S., Eddington, D.K., and Dobelle, W.H. (1974). The topography and variability
      of the primary visual cortex in man. J Neurosurg, 40(6):747-755; Rademacher, J.,
      Caviness, V.S., Steinmetz, H., and Galaburda, A.M. (1993). Topographical
      variation of the human primary cortices: implications for neuroimaging, brain
      mapping, and neurobiology. Cereb Cortex, 3(4):313-329] suggested a consistent
      relationship between V1 and the surrounding cortical folds. Here, the
      relationship between folds and the location of V1 is quantified using surface
      based analysis to generate a probabilistic atlas of human V1. High-resolution
      (about 200 microm) magnetic resonance imaging (MRI) at 7 T of ex vivo human
      cerebral hemispheres allowed identification of the full area via the stria of
      Gennari: a myeloarchitectonic feature specific to V1. Separate, whole-brain scans
      were acquired using MRI at 1.5 T to allow segmentation and mesh reconstruction of
      the cortical gray matter. For each individual, V1 was manually identified in the
      high-resolution volume and projected onto the cortical surface. Surface-based
      intersubject registration [Fischl, B., Sereno, M.I., Tootell, R.B., and Dale,
      A.M. (1999b). High-resolution intersubject averaging and a coordinate system for
      the cortical surface. Hum Brain Mapp, 8(4):272-84] was performed to align the
      primary cortical folds of individual hemispheres to those of a reference template
      representing the average folding pattern. An atlas of V1 location was constructed
      by computing the probability of V1 inclusion for each cortical location in the
      template space. This probabilistic atlas of V1 exhibits low prediction error
      compared to previous V1 probabilistic atlases built in volumetric coordinates.
      The increased predictability observed under surface-based registration suggests
      that the location of V1 is more accurately predicted by the cortical folds than
      by the shape of the brain embedded in the volume of the skull. In addition, the
      high quality of this atlas provides direct evidence that surface-based
      intersubject registration methods are superior to volume-based methods at
      superimposing functional areas of cortex and therefore are better suited to
      support multisubject averaging for functional imaging experiments targeting the
      cerebral cortex.

PMID- 18055225
TI  - Molecular phylogeny and biogeography of the Neotropical cichlid fish tribe
      Cichlasomatini (Teleostei: Cichlidae: Cichlasomatinae).
AB  - We have conducted the first comprehensive molecular phylogeny of the tribe
      Cichlasomatini including all valid genera as well as important species of
      questionable generic status. To recover the relationships among cichlasomatine
      genera and to test their monophyly we analyzed sequences from two mitochondrial
      (16S rRNA, cytochrome b) and one nuclear marker (first intron of S7 ribosomal
      gene) totalling 2236 bp. Our data suggest that all genera except Aequidens are
      monophyletic, but we found important disagreements between the traditional
      morphological relationships and the phylogeny based on our molecular data. Our
      analyses support the following conclusions: (a) Aequidens sensu stricto is
      paraphyletic, including also Cichlasoma (CA clade); (b) Krobia is not closely
      related to Bujurquina and includes also the Guyanan Aequidens species A.
      potaroensis and probably A. paloemeuensis (KA clade). (c) Bujurquina and
      Tahuantinsuyoa are sister groups, closely related to an undescribed genus formed
      by the 'Aequidens'pulcher-'Aequidens'rivulatus groups (BTA clade). (d) Nannacara
      (plus Ivanacara) and Cleithracara are found as sister groups (NIC clade).
      Acaronia is most probably the sister group of the BTA clade, and Laetacara may be
      the sister group of this clade. Estimation of divergence times suggests that the
      divergence of Cichlasomatini started around 44Mya with the vicariance between
      coastal rivers of the Guyanas (KA and NIC clades) and remaining cis-andean South
      America, followed by evolution of the Acaronia-Laetacara-BTA clade in Western
      Amazon, and the CA clade in the Eastern Amazon. Vicariant divergence has played
      importantly in evolution of cichlasomatine genera, with dispersal limited to
      later range extension of species within genera.

PMID- 18055226
TI  - Maternal smoking, alcohol drinking, and febrile convulsion.
AB  - BACKGROUND: Previous studies have suggested that maternal cigarette smoking and
      alcohol drinking during pregnancy may increase risk for febrile convulsion during
      childhood. We evaluated the relationship of maternal smoking, alcohol drinking,
      and their interaction on febrile convulsion. METHOD: Pregnant women (n=10,108)
      enrolled in the Child Health and Development Studies in California between 1959
      and 1966 were interviewed about their habits during pregnancy and febrile
      convulsions of the child were ascertained soon after an event. RESULTS: Febrile
      convulsions were reported in 2.9% of children of mothers who both smoked and
      drank alcohol, 2.0% for children of mothers who smoked but did not drink, 1.5%
      for children of mothers who drank but did not smoke and 2.1% of children of
      mothers who neither smoked nor drank. After adjusting for covariates, children of
      smokers who did not drink and children of drinkers who did not smoke did not have
      a significant hazard for febrile convulsion, compared to children of non-smokers
      non-drinkers. However, children of smokers who drank had a 30% increased hazard
      of febrile convulsion (95% CI=1.0, 1.9). The interaction term for smoking and
      alcohol drinking was significant in the multivariable model (p=0.02). CONCLUSION:
      These results suggest that children of mothers who both smoke and drink alcohol
      during pregnancy may have a higher risk for febrile convulsions.

PMID- 18055224
TI  - Phylogeography of Diadophis punctatus: extensive lineage diversity and repeated
      patterns of historical demography in a trans-continental snake.
AB  - Dynamic climatic oscillations during the Pleistocene had profound effects on the
      distributions of species across North America. Although the role of historical
      climate change on speciation remains controversial, the impact on genetic
      variation within species has been well documented. We examined mtDNA sequences
      from the cytochrome b gene (1117 bp) and a portion of the NADH-4 gene (659 bp)
      for 286 individuals of Diadophis punctatus to infer phylogeographic patterns and
      population structure and to examine historical demographic patterns in both
      glaciated and unglaciated regions of North America. We inferred 14 lineages that
      replace each other geographically across the United States. Several of these
      lineages appear to be confined to specific habitats (floodplains, grasslands,
      montane environments) and traverse previously identified genetic barriers for
      terrestrial vertebrates including the Mississippi and Apalachicola Rivers, the
      Appalachian Mountains, and the western continental divide. We also observed
      overlapping ranges between some haplotype groups and several instances of
      secondary contact associated with ecological transition zones in eastern South
      Carolina, southern Oklahoma and central California. Within the US,
      diversification began during the late Miocene and continued into the mid
      Pleistocene, suggesting these lineages pre-dated the last glacial maximum.
      Coalescent and non-coalescent demographic analyses indicate that independent
      lineages currently occupying previously glaciated or unsuitable areas in eastern,
      central and western US underwent post-glacial population expansion likely from
      southern refugia during the late Pleistocene/early Holocene. Conversely, southern
      lineages display patterns consistent with long-term population stability. Such
      long-term persistence of genetic structure may be due to the competitive effects
      between lineages or ecosystem stability in more southern latitudes.

PMID- 18055227
TI  - Should we reconsider epilepsy surgery? The motivation of patients once rejected.
AB  - The pre-surgical work-up of patients with medically refractory epilepsy changes
      with the availability of new diagnostic procedures. New diagnostic investigations
      may also open up prospects for patients rejected in the past. A cohort of 71
      Dutch patients rejected for epilepsy surgery 0.5-5 years earlier were approached
      to evaluate their willingness to undergo novel techniques. 64 (90%) responded to
      a questionnaire evaluating social and medical status, quality of life (QoL) and
      motivation to be reconsidered for epilepsy surgery. Four patients (6%) did not
      have seizures during the last 6 months. 56 patients (88%) were highly motivated
      to undergo new diagnostic procedures. Inability to localize the seizure focus had
      been the reason for rejection in 70% of these. We conclude that most patients
      once rejected for epilepsy surgery would like to benefit from novel techniques.

PMID- 18055228
TI  - Does assimilation into schemas involve systems or cellular consolidation? It's
      not just time.
AB  - A comment by Rudy and Sutherland [Rudy, J. R., & Sutherland, R. J. (2008). Is it
      systems or cellular consolidation? Time will tell. An alternative interpretation
      of the Morris Group's recent Science Paper. Neurobiology of Learning and Memory]
      has suggested an alternative account of recent findings concerning very rapid
      systems consolidation as described in a recent paper by Tse et al [Tse, D.,
      Langston, R. F., Kakeyama, M., Bethus, I., Spooner, P. A., & Wood, E. R., et al.
      (2007). Schemas and memory consolidation. Science, 316, 76-82]. This is to
      suppose that excitotoxic lesions of the hippocampus cause transient disruptive
      neural activity outside the target structure that interferes with cellular
      consolidation in the cortex. We disagree with this alternative interpretation of
      our findings and cite relevant data in our original paper indicating why this
      proposal is unlikely. Various predictions of the two accounts are nonetheless
      outlined, together with the types of experiments needed to resolve the issue of
      whether systems consolidation can occur very rapidly when guided by activated
      neural schemas.

PMID- 18055229
TI  - Human leukocyte antigen-B-associated transcript 3 is released from tumor cells
      and engages the NKp30 receptor on natural killer cells.
AB  - The activity of natural killer (NK) cells is regulated by surface receptors,
      which direct target cell recognition. NKp30 (Natural Cytotoxicity Receptor 3)
      induces target cell lysis and is also crucial for the interaction with dendritic
      cells. So far, the cellular ligands for NKp30 have remained elusive. Here we show
      that the nuclear factor HLA-B-associated transcript 3 (BAT3) was released from
      tumor cells, bound directly to NKp30, and engaged NKp30 on NK cells. BAT3
      triggered NKp30-mediated cytotoxicity and was necessary for tumor rejection in a
      multiple myeloma model. These data identify BAT3 as a cellular ligand for NKp30.
      We propose a concept for target cell recognition by NK cells beyond "missing
      self" and "induced self," mediated through a tumor cell-derived extracellular
      factor.

PMID- 18055231
TI  - The nadA gene of Aspergillus nidulans, encoding adenine deaminase, is subject to
      a unique regulatory pattern.
AB  - The adenine deaminase of A. nidulans, encoded by nadA, can be considered both as
      a catabolic and a purine salvage enzyme. We show that its transcriptional
      regulation reflects this double metabolic role. As all other genes involved in
      purine utilisation it is induced by uric acid, and this induction is mediated by
      the UaY transcription factor. However, it is also independently and
      synergistically induced by adenosine by a UaY-independent mechanism. At variance
      with all other enzymes of purine catabolism it is not repressed but induced by
      ammonium. This is at least partly due to the ammonium responsive GATA factor,
      AreA, acting in the nadA promoter as a competitor rather than in synergy with
      UaY. The adB gene, encoding adenylo-succinate synthetase, which can be considered
      both a biosynthetic and a salvage pathway enzyme, shares with nadA both ammonium
      and adenosine induction.

PMID- 18055230
TI  - microRNA-155 regulates the generation of immunoglobulin class-switched plasma
      cells.
AB  - microRNA-155 (miR-155) is expressed by cells of the immune system after
      activation and has been shown to be required for antibody production after
      vaccination with attenuated Salmonella. Here we show the intrinsic requirement
      for miR-155 in B cell responses to thymus-dependent and -independent antigens. B
      cells lacking miR-155 generated reduced extrafollicular and germinal center
      responses and failed to produce high-affinity IgG1 antibodies. Gene-expression
      profiling of activated B cells indicated that miR-155 regulates an array of genes
      with diverse function, many of which are predicted targets of miR-155. The
      transcription factor Pu.1 is validated as a direct target of miR155-mediated
      inhibition. When Pu.1 is overexpressed in wild-type B cells, fewer IgG1 cells are
      produced, indicating that loss of Pu.1 regulation is a contributing factor to the
      miR-155-deficient phenotype. Our results implicate post-transcriptional
      regulation of gene expression for establishing the terminal differentiation
      program of B cells.

PMID- 18055232
TI  - Factors influencing diagnosis delay in children with Tourette syndrome.
AB  - BACKGROUND: Tourette syndrome (TS) is a chronic disorder characterized by motor
      and vocal tics. Previous studies reported a substantial lag period between
      disease onset and diagnosis ranging from 3 to 11.9 years. AIMS: To determine the
      lag period and factors associated with diagnosis delay of TS. METHODS: All files
      of 185 children with TS attending one neuropediatric unit in Jerusalem were
      reviewed. Lag time between disease onset, according to DSM criteria, and
      diagnosis was determined and the contributions of the disease course,
      comorbidities and epidemiological factors were assessed. RESULTS: A relatively
      short lag to diagnosis following the onset of diagnosable TS was documented (mean
      13.2+/-15.9 months, median 6 months). A relatively longer gap was associated with
      older age at TS onset (r=0.161, p<0.05) and vocal tics as the first manifestation
      rather than motor or combined motor and vocal tics (mean=20.3+16.3 months vs
      11.9+16.5 and 12.6+15.2, respectively, p<0.05). A relatively shorter gap was
      associated with tic severity (r=0.13, p<0.05) and presence of comorbid obsessive
      compulsive disorder (OCD) (9.5+14.7 months vs. 14.1+16 without OCD, p<0.05).
      CONCLUSIONS: Lag time to diagnosis is relatively short in our population. Factors
      associated with a shorter lag (early age of TS onset, motor tics as the first
      manifestation, greater tics severity and the presence of OCD) may be perceived as
      disruptive, prompting patient and families to seek medical care. Conversely,
      vocal tics as the first manifestation, associated with a longer lag, may be
      misdiagnosed as features of common pediatric conditions, thus delaying diagnosis.

PMID- 18055233
TI  - Swallowing difficulties in Duchenne muscular dystrophy: indications for feeding
      assessment and outcome of videofluroscopic swallow studies.
AB  - Feeding difficulties are known to occur with advancing age in Duchenne muscular
      dystrophy (DMD). We evaluated the role of videofluoroscopy swallow study (VFSS)
      in a group of 30 DMD patients with feeding difficulties. Indications for feeding
      assessment were: respiratory infections potentially attributable to aspiration
      (n=10) and/or episodes of choking (n=24) subdivided into isolated choking events
      (n=8) and regular choking during swallowing (n=16). Indications for assessment
      were analysed in relation to the VFSS results. Median age at assessment was 17.13
      years (range 6-31.4). Twenty-four VFSS were performed. Prolonged chewing and
      effortful bolus transport for solids increased with age. Swallow trigger was
      normal in the majority of cases. All patients had some post-swallow pharyngeal
      residue around the laryngeal inlet increasing in volume with age. Although this
      residue did not result in aspiration, it was worse in patients that were
      frequently choking. Three patients intermittently had penetration of the
      supraglottic space that did not reach the vocal folds during the swallow. Our
      results suggest that reported swallowing problems when assessed are not always
      associated with difficulties on VFSS. It is the oral phase of swallowing that is
      most significantly affected in DMD. The pharyngeal phase is well triggered but is
      weak with incomplete pharyngeal clearance leaving pharyngeal residue.
      Insufficient or effortful chewing coupled with weak clearance may predispose them
      to choking episodes either as a one off event or with increasing frequency with
      age. This study suggests that VFSS may not be of additional benefit to careful
      feeding history and observation in DMD with feeding difficulties.

PMID- 18055234
TI  - Tumor necrosis factor-alpha and interleukin-6 are not correlated with the
      characteristics of Complex Regional Pain Syndrome type 1 in 66 patients.
AB  - It was previously shown in a group of 9 patients with complex regional pain
      syndrome type 1 (CRPS1) that levels of the proinflammatory cytokines tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are higher in blister
      fluid from the involved side. We hypothesize that local inflammation is
      responsible for the characteristics of CRPS1. The aim of this study was to
      confirm the previous observation in a large group of CRPS1 patients, repeating
      the measurement of TNF-alpha and IL-6 in blister fluid. Furthermore, we sought to
      determine whether these cytokines are responsible for the characteristics of
      CRPS1 and characterize the relationship between cytokine levels and duration of
      the disease. Sixty-six patients with CRPS1 participated. Skin blisters were
      artificially induced for measurement of cytokines in both extremities. The
      following disease characteristics were assessed: pain and differences in
      temperature, volume, and mobility between the extremities. TNF-alpha and IL-6
      levels were significantly higher in blister fluid from the involved side.
      However, cytokine levels did not correlate with the characteristics or duration
      of the disease. Our findings confirm the presence of local inflammation in a
      population of 66 patients in the first 2 years of CRPS1. Proinflammatory
      cytokines seem to be only partly involved in the pathophysiology of CRPS1, as
      indicated by the lack of coherence between TNF-alpha and IL-6 levels and the
      signs and symptoms of inflammation and disease duration. Other inflammatory
      mediators and mechanisms, such as central sensitization, are probably involved in
      the early stages of CRPS1.

PMID- 18055235
TI  - Lycopene attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic
      pain.
AB  - Diabetic neuropathic pain, an important microvascular complication of diabetes
      mellitus is recognized as one of the most difficult types of pain to treat. The
      development of tolerance, inadequate relief and potential toxicity of classical
      antinociceptives warrant the investigation of the newer agents to relieve this
      pain. The aim of the present study was to explore the antinociceptive effect of
      lycopene and its effect on tumour necrosis factor-alpha (TNF-alpha) and nitric
      oxide (NO) release in streptozotocin induced diabetic mice. Four weeks after a
      single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested
      in the tail immersion and hot-plate assays. Diabetic mice exhibited significant
      hyperalgesia alongwith increased plasma glucose and decreased body weights as
      compared with control mice. Lycopene (1, 2 and 4 mg/kg body weight; per oral)
      treatment, from the 4th to 8th week after streptozotocin injection, significantly
      attenuated thermal hyperalgesia and the hot-plate latencies. Lycopene also
      inhibited the TNF-alpha and NO release in a dose dependent manner. These results
      indicate an antinociceptive activity of lycopene possibly through its inhibitory
      action on NO and TNF-alpha release and point towards its potential to attenuate
      diabetic neuropathic pain.

PMID- 18055236
TI  - Application of biselective refocusing soft pulses to the simplification of
      heteronuclear correlation spectra.
AB  - The biselective spin echo technique allows the signals of coupled proton pairs to
      be extracted from crowded liquid state proton NMR spectra. Its use as a
      preparation sequence in heteronuclear chemical shift correlation experiments
      requires the removal of the heteronuclear coupling interaction during the
      biselective echo time. The discrimination between coupled and uncoupled protons
      signals is achieved by double quantum filtration, which delivers antiphase
      magnetization states. The latter are not directly compatible with the design of
      an HSQC-like pulse sequence. The conversion of antiphase to in-phase
      magnetization states by a second biselective echo sequence solves this problem.
      The optimization of spin echo delays is also discussed. Lastly, the article
      presents modified HSQC and HMBC pulses sequences in which information is obtained
      solely for the biselectively selected proton pairs. A peracetylated trisaccharide
      was used as a test molecule.

PMID- 18055237
TI  - Cryogenic Q-band (35GHz) probehead featuring large excitation microwave fields
      for pulse and continuous wave electron paramagnetic resonance spectroscopy:
      performance and applications.
AB  - The construction and performance of a Q-band (35GHz) cryogenic probehead for
      pulse electron paramagnetic resonance and continuous wave electron paramagnetic
      resonance measurements with down-scaled loop gap resonators (LGRs) is presented.
      The advantage of the LGR in comparison to TE(012) resonators lies in the large
      B(1) microwave (mw) fields that can be generated with moderate input mw power. We
      demonstrated with several examples that this allows optimal performance for
      double-quantum electron coherence, HYSCORE, and hyperfine decoupling experiments
      employing matched and high turning angle mw pulses with high B(1)-fields. It is
      also demonstrated that with very low excitation power (i.e. 10-40 mW), B(1)
      fields in LGRs are still sufficient to allow short mw pulses and thus experiments
      such as HYSCORE with high-spin systems to be performed with good sensitivity. A
      sensitivity factor Lambda(rs) of LGRs with different diameters and lengths is
      introduced in order to compare the sensitivity of different resonant structures.
      The electromagnetic field distribution, the B(1)-field homogeneity, the E(1)
      field strength, and the microwave coupling between wave guide and LGRs are
      investigated by electromagnetic field calculations. The advantage and application
      range using LGRs for small sample diameters is discussed.

PMID- 18055238
TI  - 3D-QSAR CoMFA analysis of C5 substituted pyrrolotriazines as HER2 (ErbB2)
      inhibitors.
AB  - Human cancers are characterized by an up-regulation of some of the RTKs (EGFR and
      HER2) and have been clinically validated as targets for cancer therapy. C4 and C5
      substituted pyrrolotriazines showed dual inhibition of HER2 and EGFR protein
      tyrosine kinases. To explore the relationship between the structures of the
      aforementioned classes of molecules and their HER2 inhibition, 3D-QSAR CoMFA
      analysis have been performed. The developed CoMFA model showed statistically
      significant results with good predictive ability.

PMID- 18055239
TI  - Depletion of high energy phosphates implicates post-exercise mortality in carp
      and trout; an in vivo 31P-NMR study.
AB  - As in vivo 31P-Nuclear Magnetic Resonance spectroscopy is currently the state of
      the art method to measure continuously intracellular pH (pH(i)) and energy status
      of muscle tissue, we used this method to study the recovery from exhaustive
      exercise. The biochemical changes during recovery are not well understood and it
      was suggested that post-exercise mortality could be caused by low pH(i); other
      studies however indicate that energy depletion might be more important. To
      analyse the mechanism of post-exercise recovery pH(i), ATP, P(i), and PCr must be
      measured at the same time, which is possible using in vivo 31P-NMR. Common carp
      and rainbow trout of about 100 g were exercised to exhaustion in a swim tunnel.
      After swimming 10 h at 1.5 body lengths (BL)/s (aerobic control), 50% of the fish
      were forced to swim at 6 BL/s until exhaustion. Recovery of energy rich
      phosphates was found to be faster in carp (1.2-1.9 h) than in trout (1.5-2.3 h).
      The same applied for the recovery from acidosis, which took 1.75 h in carp and
      5.75 h in trout. In parallel experiments the energy phosphates and lactate levels
      were measured in liver, red muscle, and white muscle. Exhaustion caused a
      significant drop in the energy status of red and white muscle tissue of trout and
      carp (corroborates NMR data), while no change at all was observed in liver
      tissue. The lactate levels were increased in the muscle but not in liver and
      blood. While all experimental animals looked healthy after exhaustion, 40-50% of
      the carp as well as trout died during the recovery phase. The energy status of
      those individuals measured by 31P-NMR was much lower than that of the survivors,
      while in contrast there was no difference in pH(i). Thus, it appears that not
      acidosis but depletion of high energy phosphates disabled muscle function and
      therefore may have been the cause of death of the non-survivors.

PMID- 18055240
TI  - Goat vitronectin: characterization and binding to Staphylococcus aureus.
AB  - Vitronectin (Vn) is a multifunctional protein present in plasma and in the
      extracellular matrix. Previous studies have demonstrated binding of many bacteria
      to human Vn. In this study, we have characterized goat Vn and studied its
      interaction with S. aureus considering the importance of this bacterium in animal
      husbandry. Goat Vn possesses two RGD motifs, at positions 45 and 106, and two
      multimerization sites that were identified from the recombinant fragments of the
      protein. The first site was localized at the N-terminus of the protein and the
      second at the C-terminus that did not require a full heparin-binding region, as
      partial deletion of this site did not affect multimerization. The 40 kDa N
      terminal fragment, Vn1-200, supported S. aureus binding. Similarly, two fragments
      representing the C-terminus of the protein (35 kDa Vn183-444 and the 22 kDa Vn323
      444) with complete heparin-binding site also supported S. aureus binding whereas
      the 14 kDa fragment, Vn363-444, with truncated heparin-binding site did not.
      Thus, a complete heparin-binding site at the C-terminus of Vn is essential for S.
      aureus binding. Maximum S. aureus binding was observed with Vn isolated by
      immunoaffinity chromatography, which predominantly consisted of multimers. This
      observation is significant considering the fact that the multimeric Vn is a
      component of the matrix surrounding the cells and may play an important part in
      initial bacterial adhesion and subsequent colonization.

PMID- 18055241
TI  - cDNA cloning and characterization of temperature-acclimation-associated light
      meromyosins from grass carp fast skeletal muscle.
AB  - The three types of cDNA clones, previously defined as the 10 degrees C,
      intermediate and 30 degrees C-types [Tao, Y., Kobayashi, M., Liang, C.S.,
      Okamoto, T., Watabe, S., 2004. Temperature-dependent expression patterns of grass
      carp fast skeletal myosin heavy chain genes. Comp. Biochem. Physiol. B 139, 649
      656], were determined for their 5'-regions which encoded at least the C-terminal
      half of myosin rod, light meromyosin (LMM), in fast skeletal muscles of grass
      carp Ctenopharyngodon idella. The deduced amino acid sequence identity was 91.1%
      between the 10 degrees C and 30 degrees C-types and 91.4% between the 10 degrees
      C and intermediate-types, whereas a high sequence identity of 97.8% was found
      between the intermediate and 30 degrees C-types. These three grass carp LMMs all
      had a characteristic seven-residue (heptad) repeat (a, b, c, d, e, f, g)(n),
      where positions a and d were normally occupied by hydrophobic residues, and
      positions b, c and f by charged residues. However, the ratios of hydrophobic
      residues to the total were higher for the intermediate- and 30 degrees C- than 10
      degrees C-type LMM, suggesting that the former both types may form more stable
      coiled-coils of alpha-helices than the latter type. These differences in the
      primary structures of LMM isoforms might be partially implicated in differences
      in the thermostabilities and gel-forming profiles of myosins from grass carp in
      different seasons reported previously [Tao, Y., Kobayashi, M., Fukushima, H.,
      Watabe, S., 2005. Changes in enzymatic and structural properties of grass carp
      fast skeletal myosin induced by the laboratory-conditioned thermal acclimation
      and seasonal acclimatization. Fish. Sci. 71, 195-204; Tao, Y., Kobayashi, M.,
      Fukushima, H., Watabe, S., 2007. Changes in rheological properties of grass carp
      fast skeletal myosin induced by seasonal acclimatization. Fish. Sci. 73, 189
      196].

PMID- 18055242
TI  - Screening of hibernation-related genes in the brain of Rhinolophus ferrumequinum
      during hibernation.
AB  - The greater horseshoe bat (Rhinolophus ferrumequinum) is a widely distributed
      small mammal that hibernates annually. A systematic study was initiated to
      identify differentially expressed genes in hibernating and aroused states of the
      greater horseshoe bat brain by using suppressed subtractive hybridization
      technique and dot blot. Forty-one over-expressed ESTs in the hibernating state
      were found and 17 were known genes reported in NCBI. Among these 17 genes, three
      were further checked by real time PCR. The bioinformatics analysis suggests that
      the major over-expressed ESTs may be responsible for the regulation of cell cycle
      and apoptosis, the growth of neurons, signal transduction and neuroprotection,
      gene expression regulation, and intracellular trafficking.

PMID- 18055243
TI  - Antibacterial action of L-amino acid oxidase from the skin mucus of rockfish
      Sebastes schlegelii.
AB  - L-amino acid oxidase (LAO) shows broadly antibacterial activity against Gram
      positive and Gram-negative bacteria by H(2)O(2) generated in the oxidative
      process of L-amino acids. However, LAO (termed SSAP) isolated from the rockfish
      Sebastes schlegelii skin mucus acted selectively on Gram-negative bacteria.
      Therefore, this study was undertaken to clarify the antibacterial action of SSAP
      as compared with H(2)O(2). SSAP inhibited potently the growth of Aeromonas
      salmonicida, Photobacterium damselae subsp. piscicida and Vibrio parahaemolyticus
      with a minimum inhibitory concentration (MIC) of 0.078, 0.16 and 0.63 microg/mL,
      respectively. H(2)O(2) inhibited the growth of both Gram-positive and Gram
      negative bacteria with an MIC ranging from 0.31 to 2.5 mM. When SSAP was
      incubated with P. damselae subsp. piscicida and Escherichia coli, SSAP was
      demonstrated to bind to P. damselae subsp. piscicida but not to E. coli by
      Western blotting and LAO activity measurement. These results show that the
      bacteria binding activity may be involved in the bacterial cell selectivity of
      SSAP. Electron microscopic observation of A. salmonicida, P. damselae subsp.
      piscicida and V. parahaemolyticus revealed that the treatments with SSAP and
      H(2)O(2) induced cell surface damage to A. salmonicida, remarkable elongation of
      P. damselae subsp. piscicida bodies and pores into V. parahaemolyticus cells.

PMID- 18055244
TI  - Variants in the FTO gene are associated with common obesity in the Belgian
      population.
AB  - Three independent studies, of which two genome-wide scans, have reported an
      association between SNPs in the FTO (Fat mass and obesity associated) gene and
      obesity, in different European cohorts. We selected the SNPs with the strongest
      evidence for association from the first two studies and genotyped 1099 obese
      patients and 268 healthy control individuals. Both SNPs were significantly
      associated with obesity, enabling us to replicate earlier findings from Caucasian
      cohorts in a Belgian population sample.

PMID- 18055245
TI  - The globalization of leptospirosis: worldwide incidence trends.
AB  - OBJECTIVES: Leptospirosis continues to be a significant zoonosis of the
      developing world. Globalization, in the context of international travel,
      particularly for recreational activities and military expeditions, has led to
      increased exposure of individuals from the developed world to the disease, as
      recent outbreaks show. METHODS: We evaluated the trends in annual leptospirosis
      incidence for individual countries worldwide through reports from national and
      international organizations, the published medical literature on the subject, and
      web searches with the terms 'leptospirosis' and the individual country names.
      Inter-country variations in leptospirosis incidence, when relevant official data
      were available, were also analyzed. RESULTS: The Caribbean and Latin America, the
      Indian subcontinent, Southeast Asia, Oceania, and to a lesser extent Eastern
      Europe, are the most significant foci of the disease, including areas that are
      popular travel destinations. CONCLUSIONS: Leptospirosis is a re-emerging zoonosis
      of global importance and unique environmental and social correlations. Attempts
      at global co-ordination and recognition of the true burden of an infectious
      disease with significant mortality should be encouraged.

PMID- 18055246
TI  - Folate and vitamin B12 levels in levodopa-treated Parkinson's disease patients:
      their relationship to clinical manifestations, mood and cognition.
AB  - We tested the hypothesis that mood, clinical manifestations and cognitive
      impairment of levodopa-treated Parkinson's disease (PD) patients are associated
      with vitamin B12 and folate deficiency. To this end, we performed this cross
      sectional study by measuring serum folate and vitamin B12 blood levels in 111
      consecutive PD patients. Levodopa-treated PD patients showed significantly lower
      serum levels of folate and vitamin B12 than neurological controls, while
      depressed patients had significantly lower serum folate levels as compared to non
      depressed. Cognitively impaired PD patients exhibited significantly lower serum
      vitamin B12 levels as compared to cognitively non-impaired. In conclusion, lower
      folate levels were associated with depression, while lower vitamin B12 levels
      were associated with cognitive impairment. The effects of vitamin supplementation
      merit further attention and investigation.

PMID- 18055247
TI  - Emerging scholarship in the geographies of disability.
AB  - A recent symposium on the geographies of disability at the 2007 Association of
      American Geographers meeting attracted papers and panel contributions from 46
      researchers. In this commentary, we draw on the content of the symposium to
      discuss recent developments in disability geography scholarship. We focus on
      three broad themes that ran through many of the contributions. These are: the
      evolving parameters of disability and chronic illness; the complex relationship
      between disabilities and technologies; and the struggle for citizenship.

PMID- 18055248
TI  - Spherical harmonics-based parametric deconvolution of 3D surface images using
      bending energy minimization.
AB  - Numerical deconvolution of 3D fluorescence microscopy data yields sharper images
      by reversing the known optical aberrations introduced during the acquisition
      process. When additional prior information such as the topology and smoothness of
      the imaged object surface is available, the deconvolution can be performed by
      fitting a parametric surface directly to the image data. In this work, we
      incorporate such additional information into the deconvolution process and focus
      on a parametric shape description suitable for the study of organelles, cells and
      tissues. Such membrane-bound closed biological surfaces are often topologically
      equivalent to the sphere and can be parameterized as series expansions in
      spherical harmonic functions (SH). Because image data are noisy and the SH
      parameterization is prone to the formation of high curvatures even at low
      expansion orders, the parametric deconvolution problem is ill-posed and must be
      regularized. We use the shape bending energy as a regularizing (smoothing)
      function, and determine the regularization parameter graphically with the help of
      the L-curve method. We demonstrate the complete deconvolution scheme, including
      the initial image segmentation, the calculation of a good starting surface and
      the construction of the L-curve, using real and synthetic image data.

PMID- 18055249
TI  - Chemometrics-assisted spectrophotometric methods for simultaneous determination
      and complexation study of Fe(III), Al(III) and V(V) with morin in micellar media.
AB  - Evolutionary factor analysis (EFA) and rank annihilation factor analysis (RAFA)
      were applied to resolve the two-way equilibrium spectrophotometric data belonging
      to the complexes of Fe(III), Al(III) and V(V) with morin (3,5,7,20,40-penta
      hydroxy flavone) as chelating agent in triton X-100 micellar media. Then, partial
      least square regression combined with genetic algorithm for wavelength selection
      (GA-PLS) was used for simultaneous determination of the metal ions. The
      parameters controlling behavior of the system were investigated and optimum
      conditions were selected. The predictive abilities of partial least squares
      regression (PLS) and genetic algorithm-partial least squares regression (GA-PLS)
      were examined in simultaneous determination of ternary mixtures of metal ions
      over the concentration range of 17.0-170.0ngml(-1), 25.0-180.0ngml(-1) and 40.0
      325.0ngml(-1) for Fe(III), Al(III) and V(V), respectively. The relative standard
      errors for prediction of the ions in synthetic mixtures were lower than 5% and
      the mean recoveries in the tap water spiked samples were 104.2 and 101.7% for PLS
      and GA-PLS, respectively.

PMID- 18055250
TI  - Synthesis, spectroscopic and electrochemical studies on bis-[1,3-substituted (Cl,
      Br) phenyl-5-phenyl formazanato]nickel(II) complexes.
AB  - In this study, new 1:2 Ni complexes of 1,3-substituted phenyl-5-phenylformazans
      were synthesized with -Cl, -Br substituents in the o-, m-, p-positions of the 1
      phenyl ring and -NO2 group in the m-position of the 3-phenyl ring. Their
      structures were elucidated and spectral behaviors were investigated with the use
      of elemental analysis, GC-Mass, 1H NMR, 13C NMR, FTIR, UV-vis spectra.
      Furthermore electrochemical properties such as number of electrons transferred
      (n), diffusion coefficients (D) and possible reaction mechanism of the compounds
      were determined with the use of cyclic voltammetry, ultramicrodisc electrode and
      chronoamperometry. The relation between their absorption properties and
      electrochemical properties was examined. A linear correlation was obtained
      between Hammett substituent coefficients with lambda(max) values.

PMID- 18055251
TI  - HIV-1 seroconversion during pregnancy resulting in vertical transmission.
AB  - The uptake of antenatal HIV testing in England and Scotland improved from 33% in
      1998 to 92% in 2004 after implementing an opt-out policy. However, there is the
      potential for missing HIV seroconversion during pregnancy unless a further test
      is carried out between antenatal booking, which mostly occurs between 12-14
      weeks, and delivery. We report a 32-year old Caucasian woman who developed a
      primary symptomatic HIV infection late in pregnancy. Unfortunately, despite
      antiretroviral treatment, caesarean section and formula feeding to reduce the
      risk of mother to child transmission (MCT), the baby was found to be infected by
      12 weeks of age. Despite a 95% uptake rate at King's College Hospital, another
      HIV seroconversion during late pregnancy was detected after the partner was
      admitted with AIDS defining diagnoses. In the absence of national data on HIV
      seroconversion rates in pregnancy, further maternal HIV testing later in
      pregnancy, especially for women at-risk in an ethnically diverse area such as
      London, should be considered.

PMID- 18055252
TI  - Human bocavirus.
AB  - Human bocavirus (HBoV) was first described in 2005 in nasopharyngeal aspirates of
      children with respiratory tract infection. Multiple studies have confirmed the
      presence of HBoV in respiratory tract samples of children world-wide. HBoV has
      recently also been detected in blood and fecal samples. Most studies so far have
      studied virus prevalence, and only a few reports provide data regarding the
      linkage of HBoV to disease. These reports indicate that HBoV infection is indeed
      associated with acute respiratory tract symptoms, but also that HBoV may persist
      in the respiratory tract for a longer time than other respiratory agents,
      resulting in frequent detection of low load HBoV carriage. This phenomenon has
      complicated the use of PCR diagnostics, which has been the only available
      diagnostic method. Development of alternative diagnostic strategies such as
      serology will be important for future studies of HBoV and its association with
      disease.

PMID- 18055253
TI  - Detection of human influenza A (H1N1) and B strains with reduced sensitivity to
      neuraminidase inhibitors.
AB  - BACKGROUND: Neuraminidase inhibitors (NAIs) have been used since 2005 in France.
      OBJECTIVE: Influenza viruses isolated in hospital and community cases in winter
      2005-2006 were evaluated for their sensitivity to NAIs. STUDY DESIGN: Isolates
      were tested in duplicate with a fluorescence-based neuraminidase assay. The IC50
      for oseltamivir or zanamivir was calculated for each strain. Mean IC50 (+/-S.D.)
      are expressed in nM. Viruses with IC50 superior or very superior to the upper
      limit (mean IC50+2.5 S.D.) were considered as outliers or resistant viruses,
      respectively. HA and NA genes for outliers, resistant strains and for a few
      sensitive strains were sequenced. RESULTS: Out of 225 B isolates, one was found
      resistant to both oseltamivir and zanamivir with a D197Y mutation in NA and eight
      isolates were outliers for oseltamivir and/or zanamivir. Out of 151 A (H1N1)
      isolates, one was found resistant to oseltamivir but sensitive to zanamivir with
      a H275Y mutation in NA, two isolates were resistant to zanamivir and three
      isolates were outliers for oseltamivir and/or zanamivir. New mutations were
      detected in outliers compared to sensitive viruses. CONCLUSION: Resistant
      influenza strains to NAIs are circulating at a stable and low level of 1% since
      the introduction of NAIs in clinical practice.

PMID- 18055254
TI  - Mutations of neuraminidase implicated in neuraminidase inhibitors resistance.
AB  - Influenza constitutes one of the most important upper respiratory tract
      infections regarding morbidity, and mortality. Prevention and treatment of
      influenza rely on inactivated vaccines and antiviral drugs. Zanamivir and
      Oseltamivir, the currently available influenza neuraminidase inhibitors (NAI) can
      be used in clinical practice for the treatment of influenza infection. These
      drugs have also shown their efficacy against highly pathogenic avian influenza.
      Recent transmission of avian H7N7 and H5N1 influenza virus to human emphasized
      the need for active antiviral against emerging influenza viruses. Since their
      introduction in clinical practice, numerous studies have been implemented to
      determine the rate of emergence of NAI resistant isolates. These studies describe
      mechanisms of resistance associated to mutations in the neuraminidase protein,
      and their consequence in virus fitness and transmission. This review is
      summarizing the mutations described in human and avian influenza neuraminidases
      that are associated to resistance or reduction in sensitivity.

PMID- 18055256
TI  - Impaired cerebral oscillatory processing in hepatic encephalopathy.
AB  - OBJECTIVE: Hepatic encephalopathy (HE) is characterized by neuropsychological and
      motor deficits. The present study tested the hypothesis that worsening of motor
      and sensory symptoms of HE results from a common basic deficit in the cerebral
      oscillatory processing within the human motor and visual system. METHODS: We
      investigated in 32 patients with liver cirrhosis and HE grades 0-2 critical
      flicker frequency (CFF) and cortico-muscular (M1-EMG) coherence as a measure of
      coupling between the surface EMGs of hand muscles and primary motor cortex (M1)
      activity recorded non-invasively with magnetoencephalography (MEG) during forearm
      elevation. RESULTS: Patients with HE-grade 2 developed excessive M1-EMG coherence
      at low frequencies. In contrast, maximum M1-EMG coherence in patients with no HE
      showed frequency and amplitude in the physiological range. CFF was continuously
      reduced with worsening grades of HE. Correlation analysis revealed significant
      correlation between the frequency of M1-EMG coherence and CFF. CONCLUSIONS: Taken
      together, we demonstrate that increased grades of HE lead to a pathological M1
      EMG drive which is reduced in frequency. These effects are correlated with an
      impaired perception of oscillatory visual stimuli. SIGNIFICANCE: The results
      suggest that pathological oscillatory neural processing in different human
      cerebral systems may represent a basic mechanism for the clinical manifestation
      of HE.

PMID- 18055255
TI  - The auditory P50 component to onset and offset of sound.
AB  - OBJECTIVE: The auditory Event-Related Potentials (ERP) of component P50 to sound
      onset and offset have been reported to be similar, but their magnetic homologue
      has been reported absent to sound offset. We compared the spatio-temporal
      distribution of cortical activity during P50 to sound onset and offset, without
      confounds of spectral change. METHODS: ERPs were recorded in response to onsets
      and offsets of silent intervals of 0.5 s (gaps) appearing randomly in otherwise
      continuous white noise and compared to ERPs to randomly distributed click pairs
      with half second separation presented in silence. Subjects were awake and
      distracted from the stimuli by reading a complicated text. Measures of P50
      included peak latency and amplitude, as well as source current density estimates
      to the clicks and sound onsets and offsets. RESULTS: P50 occurred in response to
      noise onsets and to clicks, while to noise offset it was absent. Latency of P50
      was similar to noise onset (56 ms) and to clicks (53 ms). Sources of P50 to noise
      onsets and clicks included bilateral superior parietal areas. In contrast, noise
      offsets activated left inferior temporal and occipital areas at the time of P50.
      Source current density was significantly higher to noise onset than offset in the
      vicinity of the temporo-parietal junction. CONCLUSIONS: P50 to sound offset is
      absent compared to the distinct P50 to sound onset and to clicks, at different
      intracranial sources. P50 to stimulus onset and to clicks appears to reflect
      preattentive arousal by a new sound in the scene. Sound offset does not involve a
      new sound and hence the absent P50. SIGNIFICANCE: Stimulus onset activates
      distinct early cortical processes that are absent to offset.

PMID- 18055257
TI  - Auditory event-related potentials in non-demented patients with sporadic
      amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To investigate the presence of sub-clinical cognitive dysfunction in
      non-demented patients with amyotrophic lateral sclerosis (ALS) using auditory
      event-related potentials (ERPs). METHODS: Ten subjects with ALS and 10 age- and
      sex-matched controls performed a passive three-stimulus paradigm with standard
      (80%), deviant (16%) and distracter (4%) stimuli. To quantify the mismatch
      component, the evoked response to the standard tones was subtracted from the
      corresponding deviant stimuli and novel response; the P3a component was obtained
      by subtracting the response to the standard tone from that to the novel stimuli.
      The amplitude and latency for the N1 component obtained with the standard stimuli
      were also measured. Clinical features, disability, cognitive status and
      depression were evaluated with standardised scales. RESULTS: There were no
      significant differences between patients and controls for latencies, while the
      N1, P3a and MMN (obtained by the subtraction Novel-Standard) were of lower
      amplitude in patients than in controls. In the patient group, the P3a latency
      correlated with months from disease onset and symptoms severity, measured with
      the amyotrophic lateral sclerosis severity scale. CONCLUSIONS: Our findings
      confirm the hypothesis of a sub-clinical cognitive impairment in non-demented ALS
      patients, suggesting pathological involvement beyond the motor areas.
      SIGNIFICANCE: ERPs seem to be a promising technique to detect the possible
      impairment of extra-motor sub-clinical dysfunction in ALS, and an appropriate
      technique for the cognitive follow-up, as passive tasks, not requiring motor
      responses, are particularly adequate in a disorder leading to severe loss of
      motor function.

PMID- 18055259
TI  - Physiological and anthropometric characteristics of junior elite and sub-elite
      rugby league players, with special reference to starters and non-starters.
AB  - While several studies have documented the physiological and anthropometric
      characteristics of senior rugby league players, investigations of the physical
      qualities of junior rugby league players are limited. The purpose of this study
      was to investigate the physical qualities of junior rugby league players
      competing at the elite and sub-elite level, and determine if pre-season fitness
      measures were significantly different for the players selected to play in the
      first game of the season (i.e. starters) compared to the players not selected
      (i.e. non-starters). Thirty-six junior sub-elite and 28 junior elite rugby league
      players participated in this study. All sub-elite players were registered with
      the same junior recreational rugby league club, while elite players were members
      of a National Rugby League club junior development program. Subjects underwent
      measurements of anthropometry (height, body mass, and sum of seven skinfolds),
      speed (10m, 20m, and 40m sprint), change of direction speed (505 test), estimated
      lower body power (vertical jump), and estimated maximal aerobic power (multi
      stage fitness test) at the beginning of the competitive season. Elite players had
      better developed speed, change of direction speed, vertical jump, and maximal
      aerobic power than sub-elite players. Elite starters were taller and heavier than
      non-starters, while sub-elite starters were taller and had greater change of
      direction speed than non-starters. A high estimated maximal aerobic power was a
      common discriminator between starters and non-starters for both elite and sub
      elite competitors. These findings demonstrate that some physical qualities can
      discriminate starters and non-starters in elite and sub-elite junior rugby league
      teams.

PMID- 18055258
TI  - Leg sympathetic response to noxious skin stimuli is similar in high and low level
      human spinal cord injury.
AB  - OBJECTIVE: To determine if sympathetically mediated vasoconstriction in the lower
      extremities is injury level dependent. Although sympathetic responses have been
      measured in the limbs of people with high and low level SCI using blood flow
      measurements, including Doppler ultrasound and venous plethysmography, a direct
      comparison between injury levels has not been made. METHODS: Volunteers with
      chronic SCI were grouped according to injury level. Above T6: high level (HL,
      n=7), and T6 and below: low level (LL, n=6). All subjects had complete motor and
      sensory loss. Leg arterial flows were recorded by venous occlusion
      plethysmography, and continuous heart rate and mean arterial pressure (MAP) were
      measured. The conditioning stimulus consisted of transcutaneous stimulation to
      the arch of the contralateral foot. RESULTS: HL and LL subjects demonstrated a
      significant decrease in arterial conductance during stimulation with no
      significant difference found between groups. As expected, only group HL
      demonstrated a significant increase in MAP. CONCLUSIONS: These results support
      our hypothesis that local (leg) sympathetic responses are similar for both high
      and low level SCI. SIGNIFICANCE: While low level SCI does not typically present
      with autonomic dysreflexia, bouts of increased reflex sympathetic activity could
      have ramifications for metabolism as well as renal and motor system function.

PMID- 18055260
TI  - Effects of active warm up on thermoregulation and intermittent-sprint performance
      in hot conditions.
AB  - This study examined the effects of active warm up on thermoregulatory responses
      and intermittent-sprint cycle performance in hot conditions (35.5+/-0.6 degrees
      C, RH 48.7+/-3.4%). Eight trained males performed a 36-min, intermittent-sprint
      test (IST) after no (WUP 0), 10-min (WUP 10) or 20-min warm up (WUP 20). The IST
      contained 2-min blocks consisting of a 4-s sprint, 100s active recovery and 20s
      passive rest. Twice during the IST, there was a repeated-sprint bout (RSB)
      comprising five, 2-s sprints separated by approximately 20s. There were no
      significant differences between trials for mean work (3870+/-757 versus 4028+/
      562 versus 3804+/-494Jsprint(-1)), peak power (W) or work decrement (%). However,
      mean work was significantly less in RSB2 than RSB1 for WUP 20 only (P<0.05).
      Plasma lactate was significantly higher after active warm up (WUP 20=WUP 10>WUP
      0; P<0.05), but not significantly different between conditions following either
      RSB. Rectal temperature (T(re)) was significantly higher after active warm up
      (37.0+/-0.3 versus 37.3+/-0.3 versus 37.7+/-0.1 degrees C for WUP0, WUP10 and
      WUP20, respectively) and throughout the IST. The longer active warm up resulted
      in a greater increase in T(re) and was associated with a decrease in short-term
      repeated-sprint ability (with incomplete recovery), but not prolonged,
      intermittent-sprint performance in the heat. As active warm up did not improve
      performance (<40min), team-sport athletes may minimise changes in T(re) (and the
      likelihood of heat illness) by avoiding excessive warm up when competing in the
      heat.

PMID- 18055261
TI  - Cardiovocal syndrome: a systematic review.
AB  - Hoarseness associated with mitral stenosis was initially described by Ortner.
      Several cardiopulmonary conditions were associated with left recurrent laryngeal
      nerve palsy over the last 100 years; thus, the syndrome is termed as cardiovocal
      syndrome or Ortner's syndrome. This study aimed to classify the various
      predisposing conditions and to explain the pathophysiology and treatment
      opportunities available for these patients.

PMID- 18055262
TI  - FGF2 in asthmatic airway-smooth-muscle-cell hyperplasia.
AB  - Airway smooth muscle (ASM)-cell hyperplasia is a cardinal feature of the
      remodeled airways in asthma and contributes to airway hyper-responsiveness.
      Several upregulated mediators are potentially involved in this architectural
      change. Recently, many investigators have turned their interest toward fibroblast
      growth factor (FGF)2. This opinion article describes the current knowledge on the
      biology of this growth factor, reviews the papers that have measured its baseline
      or allergen-induced expression in human asthmatics and summarizes observations
      supporting its role as an ASM cell mitogen. The possibility that FGF2 is involved
      in ASM-cell hyperplasia is raised, not only because it induces ASM-cell
      proliferation by itself but because of recent findings showing that FGF2 confers
      to ASM cells the ability to proliferate in response to different asthma
      mediators.

PMID- 18055263
TI  - Distinct roles for DC-SIGN+-dendritic cells and Langerhans cells in HIV-1
      transmission.
AB  - Dendritic cells (DCs) are thought to mediate HIV-1 transmission but it is
      becoming evident that different DC subsets at the sites of infection have
      distinct roles. In the genital tissues, two different DC subsets are present: the
      Langerhans cells (LCs) and the DC-SIGN(+)-DCs. Although DC-SIGN(+)-DCs mediate
      HIV-1 transmission, recent data demonstrate that LCs prevent HIV-1 transmission
      by clearing invading HIV-1 particles. However, this protective function of LCs is
      dependent on the function of the C-type lectin Langerin: blocking Langerin
      function by high virus concentrations enables HIV-1 transmission by LCs. Here, we
      will discuss the molecular mechanisms involved in HIV-1 transmission and viral
      clearance. A better understanding of these processes is crucial to understand and
      develop strategies to combat transmission.

PMID- 18055264
TI  - Interplay of parasite-driven immune responses and autoimmunity.
AB  - As more facts emerge regarding the ways in which parasite-derived molecules
      modulate the host immune response, it is possible to envisage how a lack of
      infection by agents that once infected humans commonly might contribute to the
      rise in autoimmune disease. Through effects on cells of both the innate and
      adaptive arms of the immune response, parasites can orchestrate a range of
      outcomes that are beneficial not only to parasites, in terms of facilitating
      their life cycles, but also to their host, in limiting pathology.

PMID- 18055265
TI  - Alpha-1-acid glycoprotein, its local production and immunopathological
      participation in experimental pulmonary tuberculosis.
AB  - Alpha-1-acid glycoprotein (AGP) is one of the major acute-phase proteins (APPs).
      Hepatic production and serum concentrations increase in response to systemic
      injury, inflammation, or infection. We reported previously that expression of the
      AGP gene is induced in the liver during experimental pulmonary tuberculosis.
      Since AGP may also be produced at the infection site and has some
      immunomodulatory properties, we used a model of progressive pulmonary
      tuberculosis in Balb/c mice to study the kinetics of AGP production in the lung
      and its influence on immunopathology. We found that AGP was produced in the lung
      during experimental tuberculosis. Alveolar macrophages and type II pneumocytes
      were the most important cellular sources during early infection (days 1-14). From
      day 21 postinfection, during the progressive phase of the infection, foamy
      macrophages located in pneumonic areas were the most important source of AGP and
      10-fold higher concentrations were found on day 60. In a second part of the
      study, AGP was inactivated during the progressive phase by the administration of
      specific blocking antibodies. In comparison with control infected animals,
      tuberculous mice treated with blocking AGP antibodies showed higher expression of
      interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and
      inducible nitric oxide synthase (iNOS) in association with significantly reduced
      bacillary loads and tissue damage. Thus, AGP is produced in the lung during
      experimental pulmonary tuberculosis and it has immunomodulatory activities,
      suppressing cell-mediated immunity and facilitating growth of bacilli and disease
      progression.

PMID- 18055266
TI  - Interpreting the clinical importance of treatment outcomes in chronic pain
      clinical trials: IMMPACT recommendations.
AB  - A consensus meeting was convened by the Initiative on Methods, Measurement, and
      Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for
      interpreting clinical importance of treatment outcomes in clinical trials of the
      efficacy and effectiveness of chronic pain treatments. A group of 40 participants
      from universities, governmental agencies, a patient self-help organization, and
      the pharmaceutical industry considered methodologic issues and research results
      relevant to determining the clinical importance of changes in the specific
      outcome measures previously recommended by IMMPACT for 4 core chronic pain
      outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating
      scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory
      and Brief Pain Inventory interference scales; (3) emotional functioning, assessed
      by the Beck Depression Inventory and Profile of Mood States; and (4) participant
      ratings of overall improvement, assessed by the Patient Global Impression of
      Change scale. It is recommended that 2 or more different methods be used to
      evaluate the clinical importance of improvement or worsening for chronic pain
      clinical trial outcome measures. Provisional benchmarks for identifying
      clinically important changes in specific outcome measures that can be used for
      outcome studies of treatments for chronic pain are proposed. PERSPECTIVE:
      Systematically collecting and reporting the recommended information needed to
      evaluate the clinical importance of treatment outcomes of chronic pain clinical
      trials will allow additional validation of proposed benchmarks and provide more
      meaningful comparisons of chronic pain treatments.

PMID- 18055267
TI  - Patients' self-criticism is a stronger predictor of physician's evaluation of
      prognosis than pain diagnosis or severity in chronic pain patients.
AB  - The experience of pain is influenced by patients' personality, social and
      cultural background, and patient-doctor interaction. This study examines the role
      of self-reported pain, pain diagnosis, age, gender, depression, and the
      personality trait of self-criticism (defined as individuals' tendency to set
      unrealistically high self-standards and to adopt a punitive stance toward one's
      self), in determining physicians' view of expected prognosis in response to
      chronic pain management. Before the first visit to a tertiary chronic pain
      clinic, patients provided information regarding their perceived pain, depression,
      and self-criticism. Immediately subsequent to the visit, physicians' evaluated
      expected prognosis. Participating physicians were blinded to the patient's
      psychosocial variables collected. Sixty-four patients with chronic pain (34 women
      and 30 men) with various diagnoses were included. Patients' age, gender, pain
      diagnosis, self-reported pain, and depression did not significantly correlate
      with physician's estimation of expected prognosis. In contrast, patients' self
      criticism emerged as an independent predictor of physicians' pessimism regarding
      outcome. Thus, in the chronic pain clinic setting, patients' personality, rather
      than self-reported pain experience, determines doctor's clinical judgment of
      expected prognosis. PERSPECTIVE: Chronic pain is a multimodal negative experience
      that is determined by physiological, cognitive, personological, and interpersonal
      factors. In line with this observation, we found patients' personality,
      specifically, their self-criticism, determines physicians' clinical judgment of
      expected prognosis.

PMID- 18055268
TI  - Successful cryoablation of ventricular tachycardia arising from the proximal
      right bundle branch in a child.

PMID- 18055269
TI  - Left atrial and pulmonary vein macroreentrant tachycardia associated with double
      conduction gaps: a novel type of man-made tachycardia after circumferential
      pulmonary vein isolation.
AB  - BACKGROUND: The macroreentrant tachycardia that involves the left atrium (LA) and
      the pulmonary veins (PVs) after atrial fibrillation (AF) ablation has not been
      described. OBJECTIVE: To clarify the mechanism and electrophysiological
      characteristics of this tachycardia. METHODS AND RESULTS: Eight patients
      presented with recurrent regular tachycardia after the initial procedure, which
      consisted of two circular linear lesions around the ipsilateral PVs. Clinical
      tachycardia with a cycle length of 297 +/- 38 ms presented as persistent in six
      and paroxysmal in two patients. During tachycardia, PV activation with one-to-one
      conduction from the LA to the PV was found via recovered conduction gaps in the
      previous lesions in all patients. Three-dimensional tachycardia mapping showed a
      macroreentrant pattern in two and a focal pattern in six patients. In two
      patients, mapping demonstrated an isthmus within the left common PV in one
      patient and within the right-sided PVs in another patient. In the remaining six
      patients with focal pattern, mapping demonstrated earliest atrial activation near
      the right-sided PV ostium in five patients and near the left-sided PV in one
      patient. Entrainment mapping showed that the LA and PVs were involved in the
      reentrant circuit with an isthmus between the two conduction gaps in all eight
      patients. The tachycardias were successfully terminated with a single
      radiofrequency application. No AT recurred during follow-up (12 +/- 9 months) in
      all patients. CONCLUSIONS: The LA-PV macroreentrant tachycardia involves the LA,
      PV, and the two conduction gaps in the previous lesions. Entrainment mapping is
      necessary to make the diagnosis. Ablation of this tachycardia can be facilitated
      by closing the conduction gaps.

PMID- 18055270
TI  - Atypical atrial tachycardias in patients with congenital heart disease.

PMID- 18055271
TI  - Altered ventricular stretch contributes to initiation of cardiac memory.
AB  - BACKGROUND: Cardiac memory is a change in T-wave morphology induced by
      ventricular pacing or arrhythmias that persist after resumption of normal AV
      conduction. Changing the pacemaker site from atrium to ventricle alters
      ventricular activation and the mechanical pattern of ventricular contraction.
      Either or both alterations affect T-wave configuration. OBJECTIVE: The purpose of
      this study was to study the role of altered contractile patterns on initiation of
      cardiac memory. METHODS: Isolated rabbit hearts were immersed in Tyrode's
      solution (37 degrees C) and aortically perfused at a constant pressure of 70
      mmHg. Three orthogonal quasi-ECG leads were recorded via six Ag-AgCl electrodes
      located on the walls of the bath. Hearts were paced at a constant cycle length
      from either the right atrial appendage or left ventricle lateral wall. The
      pulmonary artery was sealed, and both ventricles contracted isovolumetrically.
      Cardiac memory was quantified as T-wave vector displacement expressed as distance
      between T-wave vector peaks during atrial pacing before and after ventricular
      pacing. RESULTS: Five minutes of ventricular pacing induced significant T-wave
      vector displacement that returned to control in 5 to 10 minutes. No significant
      changes in intraventricular pressure occurred during and after ventricular
      pacing. Interventions that decreased ventricular load (shunting both ventricles
      to the bath) or contractility (excitation-contraction uncoupler blebbistatin)
      significantly decreased developed pressure and eliminated T-wave vector
      displacement. Neither intervention affected ventricular activation during
      ventricular pacing. Locally applied left ventricular epicardial stretch induced T
      wave vector displacement similar to that induced by ventricular pacing.
      CONCLUSION: Altered ventricular activation during ventricular pacing initiates
      cardiac memory via induction of altered contractile patterns and altered stretch.

PMID- 18055272
TI  - Spontaneous stellate ganglion nerve activity and ventricular arrhythmia in a
      canine model of sudden death.
AB  - BACKGROUND: Little information is available on the temporal relationship between
      instantaneous sympathetic nerve activity and ventricular arrhythmia in ambulatory
      animals. OBJECTIVE: The purpose of this study was to determine if increased
      sympathetic nerve activity precedes the onset of ventricular arrhythmia. METHODS:
      Simultaneous continuous long-term recording of left stellate ganglion (LSG) nerve
      activity and electrocardiography was performed in eight dogs with nerve growth
      factor infusion to the LSG, atrioventricular block, and myocardial infarction
      (experimental group) and in six normal dogs (control group). RESULTS: LSG nerve
      activity included low-amplitude burst discharge activity (LABDA) and high
      amplitude spike discharge activity (HASDA). Both LABDA and HASDA accelerated
      heart rate. In the experimental group, most ventricular tachycardia (86.3%) and
      sudden cardiac death were preceded within 15 seconds by either LABDA or HASDA.
      The closer to onset of ventricular tachycardia, the higher the nerve activity.
      The majority of HASDA was followed immediately by either ventricular arrhythmia
      (21%) or QRS morphology changes (65%). HASDA occurred in a circadian pattern.
      HASDA occurred twice as often in the experimental group than in the control
      group. Electrical stimulation of LSG increased transmural heterogeneity of
      repolarization (Tpeak-end intervals) and induced either ventricular tachycardia
      or fibrillation in the experimental group but not in the control group.
      Immunohistochemical studies revealed increased synaptogenesis and nerve sprouting
      in the LSG in the experimental group. CONCLUSION: Two distinct types of LSG nerve
      activity (HASDA and LABDA) are present in the LSG of ambulatory dogs. The
      majority of malignant ventricular arrhythmias are preceded by either HASDA or
      LABDA, with HASDA particularly arrhythmogenic.

PMID- 18055273
TI  - Atrial tachycardia with group beating: what is the mechanism?

PMID- 18055274
TI  - The Logan Healthy Living Program: a cluster randomized trial of a telephone
      delivered physical activity and dietary behavior intervention for primary care
      patients with type 2 diabetes or hypertension from a socially disadvantaged
      community--rationale, design and recruitment.
AB  - BACKGROUND: Physical activity and dietary behavior changes are important to both
      the primary prevention and secondary management of the majority of our most
      prevalent chronic conditions (i.e., cardiovascular disease, hypertension, type 2
      diabetes, breast and colon cancer). With over 85% of Australian adults visiting a
      general practitioner each year, the general practice setting has enormous
      potential to facilitate wide scale delivery of health behaviour interventions.
      However, there are also many barriers to delivery in such settings, including
      lack of time, training, resources and remuneration. Thus there is an important
      need to evaluate other feasible and effective means of delivering evidence-based
      physical activity and dietary behaviour programs to patients in primary care,
      including telephone counseling interventions. METHODS: Using a cluster randomized
      design with practice as the unit of randomization, this study evaluated a
      telephone-delivered intervention for physical activity and dietary change
      targeting patients with chronic conditions (type 2 diabetes or hypertension)
      recruited from primary care practices in a socially disadvantaged community in
      Queensland, Australia. Ten practices were randomly assigned to the telephone
      intervention or to usual care, and 434 patients were recruited. Patients in
      intervention practices received a workbook and 18 calls over 12 months.
      Assessment at baseline, 4-, 12- and 18-months allows for assessment of initial
      change and maintenance of primary outcomes (physical activity and dietary
      behavior change) and secondary outcomes (quality of life, cost-effectiveness,
      support for health behavior change). CONCLUSIONS: This effectiveness trial adds
      to the currently limited number of telephone-delivered intervention studies
      targeting both physical activity and dietary change. It also addresses some of
      the shortcomings of previous trials by targeting patients from a disadvantaged
      community, and by including detailed reporting on participant representativeness,
      intervention implementation and cost-effectiveness, as well as an evaluation of
      maintenance of health behavior change.

PMID- 18055275
TI  - Hypoxia-induced vasodilation in the right coronary circulation of conscious dogs:
      role of adrenergic activation.
AB  - The role of adrenergic activation in the right coronary (RC) flow response to
      hypoxia has not been previously delineated, and limited information from left
      coronary studies is inconsistent. Seven dogs were instrumented with catheters
      implanted in the aorta and in the right ventricle to measure aortic pressure and
      right ventricular (RV) pressure, respectively. A flow transducer was placed
      around the RC artery to measure RC flow. After recovery from surgery, the dogs
      were exposed to systemic hypoxia in a Plexiglas chamber ventilated with N(2).
      Percent O(2) in the chamber was monitored, and blood samples and hemodynamic data
      were collected as chamber O(2) was progressively reduced to approximately 6%. The
      chamber was then opened, and the dog breathed room air. Phentolamine, 1 mg/kg,
      and propranolol, 2 mg/kg, were then administered via the RV catheter to achieve
      adrenergic blockade, and the hypoxia protocol was repeated. During hypoxia,
      arterial PO(2) progressively fell from 87+/-3 to 25+/-1 mmHg during untreated
      control condition and from 90+/-4 to 23+/-1 mmHg during adrenergic blockade. In
      the unblocked condition, hypoxia caused increases in aortic pressure, heart rate,
      RV pressure, and RV dP/dt(max). After adrenergic blockade, normoxic aortic
      pressure was reduced; heart rate and RV dP/dt(max) tended to be lower. Aortic
      pressure rose during hypoxia, but to lesser values than before blockade. Heart
      rate and RV dP/dt(max) also increased, but only at more severe hypoxia, and these
      values were less than before blockade. Normoxic flow and hypoxia-induced
      increases in RC flow and conductance were not altered by blockade. The
      relationship between RC conductance and RV triple product, an index of RV O(2)
      demand, was steeper after blockade. These findings indicate that in the normal,
      unblocked condition, RC flow during hypoxia is restrained by an adrenergic
      mediated increase in RC vasomotor tone.

PMID- 18055276
TI  - Impact of lung remodelling on respiratory mechanics in a model of severe allergic
      inflammation.
AB  - We developed a model of severe allergic inflammation and investigated the impact
      of airway and lung parenchyma remodelling on in vivo and in vitro respiratory
      mechanics. BALB/c mice were sensitized and challenged with ovalbumin in severe
      allergic inflammation (SA) group. The control group (C) received saline using the
      same protocol. Light and electron microscopy showed eosinophil and neutrophil
      infiltration and fibrosis in airway and lung parenchyma, mucus gland hyperplasia,
      and airway smooth muscle hypertrophy and hyperplasia in SA group. These
      morphological changes led to in vivo (resistive and viscoelastic pressures, and
      static elastance) and in vitro (tissue elastance and resistance) lung mechanical
      alterations. Airway responsiveness to methacholine was markedly enhanced in SA as
      compared with C group. Additionally, IL-4, IL-5, and IL-13 levels in the
      bronchoalveolar lavage fluid were higher in SA group. In conclusion, this model
      of severe allergic lung inflammation enabled us to directly assess the role of
      airway and lung parenchyma inflammation and remodelling on respiratory mechanics.

PMID- 18055278
TI  - A simple and sensitive liquid chromatography-tandem mass spectrometry assay for
      the quantification of ertapenem in microdialysate.
AB  - A new liquid chromatography assay with isocratic elution and tandem mass
      spectrometry detection (LC-MS/MS) using an electrospray ionization interface in
      the multiple reaction monitoring mode was developed and validated for ertapenem
      determination in microdialysate samples. Linearity was demonstrated between
      10ngmL(-1) (lower limit of quantification, LLoQ) and 160ngmL(-1). The precision
      (CV%) and accuracy (bias%) in microdialysates at the LLoQ were respectively 2.2%
      and 17.3% within-day and 10.6% and 2.7% between-days. Ertapenem was stable for 1
      month at -20 degrees C and -80 degrees C but unstable at +4 degrees C. This new
      LC-MS/MS assay is simple, rapid and more sensitive than previously described
      assays.

PMID- 18055277
TI  - Brainstem circuitry of tracheal-bronchial cough: c-fos study in anesthetized
      cats.
AB  - The c-fos gene expression method was used to localize brainstem neurons
      functionally related to the tracheal-bronchial cough on 13 spontaneously
      breathing, pentobarbitone anesthetized cats. The level of Fos-like
      immunoreactivity (FLI) in 6 animals with repetitive coughs (170+/-12) induced by
      mechanical stimulation of the tracheobronchial mucosa was compared to FLI in 7
      control non-stimulated cats. Thirty-four nuclei were compared for the number of
      labeled cells. Enhanced cough FLI was found bilaterally at following brainstem
      structures, as compared to controls: In the medulla, FLI was increased in the
      medial, interstitial and ventrolateral subnuclei of the solitary tract (p <
      0.02), in the retroambigual nucleus of the caudal medulla (p < 0.05), in the
      ambigual, paraambigual and retrofacial nuclei of the rostral medulla along with
      the lateral reticular nuclei, the ventrolateral reticular tegmental field (p <
      0.05), and the raphe nuclei (p < 0.05). In pons, increased FLI was detected in
      the lateral parabrachial and Kolliker-Fuse nuclei (p < 0.01), in the
      posteroventral cochlear nuclei (p < 0.01), and the raphe midline (p < 0.05).
      Within the mesencephalon cough-related FLI was enhanced at the rostral midline
      area (p < 0.05), but a decrease was found at its caudal part in the
      periaqueductal gray (p < 0.02). Results of this study suggest a large medullary -
      pontine - mesencephalic neuronal circuit involved in the control of the tracheal
      bronchial cough in cats.

PMID- 18055279
TI  - Development of accurate classification method based on the analysis of volatile
      organic compounds from human exhaled air.
AB  - Analysis of exhaled air leads to the development of fast accurate and non
      invasive diagnostics. A comprehensive analysis of the entire range of volatile
      organic compounds (VOCs) in exhaled air samples will enable the identification of
      VOCs unique for certain patient groups. This study demonstrates proof of
      principle of our developed method tested on a smoking/non-smoking study
      population. Thermal desorption and gas chromatography coupled to time-of-flight
      mass spectrometry were used to analyse exhaled air samples. The VOC profiles
      obtained from each individual were combined into one final database based on
      similarity of mass spectra and retention indexes (RI), which offers the
      possibility for a reliable selection of compounds of interest. As proof of
      principle we correctly classified all subjects from population of smoking (N=11)
      and non-smoking (N=11) based on the VOC profiles available in their exhaled air.
      Support vector machine (SVM) analysis identified 4 VOCs as biomarkers of recent
      exposure to cigarette smoke: 2,5-dimethyl hexane, dodecane, 2,5-dimethylfuran and
      2-methylfuran. This approach contributes to future development of fast, accurate
      and non-invasive diagnostics of inflammatory diseases including pulmonary
      diseases.

PMID- 18055280
TI  - Determination of the low molecular weight fraction of food-grade carrageenans.
AB  - Recently there has been some debate regarding the presence and associated health
      risk of low molecular weight carrageenan in foodstuffs. Unfortunately measurement
      of the low molecular weight tail (LMT) of food-grade carrageenans (defined here
      as the carrageenan having relative molecular mass (Mr) below 50,000) is not
      trivial, largely due to its low abundance. So far methods employing light
      scattering have been unsuccessful in producing reproducible results, probably due
      to the poor detector response at low masses. In this work a method based on high
      performance size exclusion chromatography coupled to a refractive index detector
      (HPSEC-RI) has been used for the measurement of the LMT in food-grade carrageenan
      ingredients and in a carrageenan-containing finished product (a jelly). Over the
      course of half a year, 19 measurements were made on a reference carrageenan; the
      results demonstrated that the method had excellent reproducibility. Applied to a
      number of different carrageenan ingredients, it was found that, in general, the
      LMT represents less than 8% of the total carrageenan in ingredients, and under
      the correct conditions increases little during food processing. The data also
      indicated that pH appears to be a critical factor during food processing and pH
      levels below 4.0 should be avoided.

PMID- 18055281
TI  - Aspartate aminotransferase to platelet ratio index (APRI) can predict liver
      fibrosis in chronic hepatitis B.
AB  - BACKGROUND: There have been still few valuable markers that can be used as
      indirect markers of liver fibrosis in chronic hepatitis B. AIMS: This study aimed
      to evaluate efficacy of several indirect markers of liver fibrosis and to
      identify the most valuable test in chronic hepatitis B. PATIENTS AND METHODS: A
      total of 264 patients with chronic hepatitis B were consecutively enrolled.
      Fibrosis was staged by a single blinded pathologist according to the METAVIR
      system. Significant fibrosis was defined as stage >or=2. We investigated
      diagnostic accuracy of four indirect markers including aspartate aminotransferase
      to platelet ratio index for predicting significant fibrosis. RESULTS: Mean age
      was 28 years. 53% (141/264) had significant hepatic fibrosis. Of indirect
      markers, aspartate aminotransferase to platelet ratio index yielded the best area
      under the receiver operating characteristic curve (0.86; 95% confidence interval,
      0.82-0.91). Positive predictive value/negative predictive value at 0.5, 1.5 and
      2.0 of aspartate aminotransferase to platelet ratio index score for predicting
      significant fibrosis were 63%/91%, 83%/74% and 86%/65%, respectively. The odds
      ratio for aspartate aminotransferase to platelet ratio index >or=1.4 relative to
      less than aspartate aminotransferase to platelet ratio index of 1.4 was 17.971
      (p<0.0001; 95% confidence interval, 9.677-33.376). CONCLUSIONS: Of simple markers
      already developed in chronic hepatitis C, aspartate aminotransferase to platelet
      ratio index may be the most accurate and simple marker for predicting significant
      fibrosis in chronic hepatitis B.

PMID- 18055282
TI  - Aorto-oesophageal fistula: save time to save life.

PMID- 18055283
TI  - The incidence of coeliac disease in adult first degree relatives.
AB  - BACKGROUND AND AIMS: Although prevalence of coeliac disease among first degree
      relatives of coeliac patients is well-known, only four studies are available
      about its incidence. We investigated whether first degree relatives found to be
      negative at a first serological screening can subsequently develop coeliac
      disease. PATIENTS AND METHODS: In the last 6 years, endomysial antibodies were
      tested in 158 adult first degree relatives referred to our coeliac out-patient
      clinic. After at least a year, negative subjects were offered a second testing.
      Sixty-three accepted. RESULTS: 130/158 first degree relatives tested negative
      initially. Although one of them had developed coeliac disease after the first
      testing, at the second testing none of the 63 endomysial antibody negative first
      degree relatives proved positive. Incidence of coeliac disease among first degree
      relatives was 1/64 in 51 months, 0.437% year (95%CI 0.05-2.62). An analysis of
      the sample size showed that 10,000 first degree relatives must be followed up to
      significantly reduce the CI. CONCLUSIONS: Although we confirmed the high
      prevalence of coeliac disease among first degree relatives (28/158, 17.7%), we
      found that the low incidence suggests that further studies are required to
      understand whether endomysial antibody negative first degree relatives need to be
      followed up.

PMID- 18055284
TI  - Acute cholestasis: atypical onset of Kawasaki disease.
AB  - Atypical onset of Kawasaki disease (KD) is a frequent problem leading to
      diagnostic mistake. Acute cholestasis and liver involvement occur occasionally as
      minor manifestation of KD. We report the case of a 6-year-old boy presenting
      fever, jaundice, abdominal pain, and ascites who subsequently developed typical
      KD clinical pattern just at the same time of echocardiographic coronary arteries
      anomalies. Abdominal radiological evaluation was normal and seroimmunologic
      markers resulted negative. Shortly after intravenous immunoglobulin and
      acetylsalicylic acid administration the clinical features disappeared. KD should
      be considered in differential diagnosis in children with cholestasis, abdominal
      pain and fever of unknown etiology.

PMID- 18055285
TI  - Q&A on diagnosis, screening and follow-up of colorectal neoplasia.
AB  - The impressive and brisk evolution of medical science prevents many physicians
      from a thorough update on all the research fields. Colorectal cancer diagnosis,
      screening and follow-up is well known to require a multi-disciplinary approach,
      as it is faced by several specialties such as primary care physicians,
      gastroenterologists, non-gastroenterologist internists, radiologists and
      surgeons. To address this issue in a mutual perspective, we focused on the main
      points of the epidemiology, diagnosis, screening and follow-up of colorectal
      neoplasia by using a simple "Question & Answers" structure.

PMID- 18055286
TI  - Identification of angiogenin as the osteoclastic bone resorption-inhibitory
      factor in bovine milk.
AB  - We identified, for the first time, the factor responsible for inhibiting
      osteoclast-mediated bone resorption in the basic protein fraction of bovine milk
      (milk basic protein, MBP). The protein was purified by a combination of ion and
      gel column chromatography from MBP, based on its activity to prevent
      unfractionated rabbit bone cells from forming pits on dentine slices. It was
      found to have a molecular weight of 15 kDa on SDS-PAGE, and the sequence of the N
      terminal 25 amino acid residues was identical to that of bovine angiogenin. The
      purified bovine angiogenin inhibited the pit-forming activity of both
      unfractionated bone cells and purified osteoclasts in a dose-dependent manner,
      and the inhibitory activity was markedly suppressed by treatment with anti-bovine
      angiogenin antibody. The inhibitory activity was confirmed in mice both in vitro
      and in vivo. Treatment of osteoclasts with bovine angiogenin resulted in an
      impairment of the formation F-actin ring and a reduction in the mRNA levels of
      TRAP and cathepsin K, both known to be essential for the bone resorption activity
      of osteoclasts. These results suggest that bovine angiogenin is the substance
      mainly responsible for the inhibitory effect of bovine milk on osteoclast
      mediated bone resorption, and that it exerts its activity by acting directly on
      the osteoclasts.

PMID- 18055287
TI  - The skeletal response to estrogen is impaired in female but not in male steroid
      receptor coactivator (SRC)-1 knock out mice.
AB  - Estrogen (E) is critical for the maintenance of bone mass in both female and male
      mice and steroid receptor coactivator (SRC)-1 has been shown to be important for
      mediating E effects on bone, at least in female mice. In the present study, we
      defined the skeletal phenotype of male SRC-1 knock out (KO) mice and compared it
      with their female littermates. Further, to determine the role of SRC-1 in
      mediating effects of E on bone in male mice, we examined the skeletal effects of
      gonadectomy (gnx) with or without E replacement in male mice and placed these
      findings in the context of our previous studies in female SRC-1 KO mice. Analysis
      of a large group of male (WT, n=67; SRC-1 KO, n=56) and female (WT, n=66; SRC-1
      KO, n=70) mice showed a significant decrease in trabecular volumetric bone
      mineral density (vBMD) in SRC-1 KO mice compared to their WT littermates in both
      genders (male SRC-1 KO, 275+/-3 vs. WT, 295+/-3 mg/cm(3), P<0.001; female SRC-1
      KO, 210+/-2 vs. WT, 221+/-2 mg/cm(3), P<0.001). Following gnx and E replacement
      (10 microg/kg/day), we previously demonstrated that SRC-1 KO female mice have a
      defect in E action in trabecular, but not in cortical bone. In contrast, we now
      demonstrate that the same dose of E administered to gnx'd male SRC-1 KO mice was
      sufficient to prevent trabecular bone loss in these mice. For example, in WT
      female mice, gnx followed by E replacement maintained spine BMD (1.2+/-3.4% vs.
      baseline) as compared to gnx without E replacement (-12.7+/-2.6%, P<0.001 vs.
      sham); this effect of E was absent in SRC-1 KO female mice. By contrast, the
      identical dose of E was equally effective in maintaining spine BMD in E-treated
      gnx'd male WT (-5.2+/-5.1% vs. baseline) and male SRC-1 KO (-5.4+/-5.3%) mice,
      respectively, as compared to gnx'd mice without E treatment (WT, -17.6+/-2.5%,
      P=0.02; SRC-1 KO, -28.6+/-2.6%, P<0.001 vs. sham). E treatment was effective in
      suppressing cancellous bone turnover in both gnx'd WT and SRC-1 KO male mice as
      determined by significant reductions in osteoblast and osteoclast numbers;
      however, in female mice, E treatment only suppressed bone turnover in WT but not
      in SRC-1 KO mice. Collectively, these findings demonstrate that loss of SRC-1
      results in trabecular osteopenia in male and female mice, but in contrast to
      female mice, this is not due to any detectable resistance to E action in
      trabecular bone in male SRC-1 KO mice.

PMID- 18055288
TI  - The role of calcium and vitamin D in the management of osteoporosis.
AB  - The role of calcium and vitamin D supplementation in the treatment of
      osteoporosis has been extensively studied. The aim of this paper was to reach,
      where possible, consensus views on five key questions relating to calcium and
      vitamin D supplementation in the management of osteoporosis. Whereas global
      strategies that target supplementation to the general population could not be
      justified in terms of efficacy and health economics, there is a clearer rationale
      for supplementing patients who are at increased risk of osteoporosis and those
      who have developed osteoporosis, including those already taking other treatments
      for osteoporosis. The combination of vitamin D with calcium may be beneficial in
      terms of efficacy and, perhaps, for optimising adherence.

PMID- 18055289
TI  - Stainless steel screws coated with bisphosphonates gave stronger fixation and
      more surrounding bone. Histomorphometry in rats.
AB  - Coating of stainless steel screws with bisphosphonate in a fibrinogen matrix
      leads to an enhancement of the pullout strength 2 weeks after insertion in rat
      tibiae. This effect then increases over time until at least 8 weeks. The pullout
      force reflects the mechanical properties of the bone within the threads, which
      acts as a screw nut. The aim of the present study was to find descriptive and
      morphometric histological correlates to the increased pullout strength. Because
      the bisphosphonates are applied via the implant surface, we also measured bone to
      implant contact and how far away from the surface any effects could be seen.
      Stainless steel screws underwent one of three treatments: uncoated control,
      controls coated with a layer of cross-linked fibrinogen, or screws further
      modified with bisphosphonates covalently linked and physically adsorbed to the
      fibrinogen layer. At 1 (n=33) and 8 (n=27) weeks, bone to implant contact and
      bone area density in the threads were measured, as well as bone area density at
      250 and 500 microm from the outer edge of the threads. Additionally, removal
      torque for each screw treatment was measured at 2 weeks (n=28). At 8 weeks, the
      part of the bisphosphonate screw that was located in the marrow cavity had become
      surrounded with bone, whereas there was almost no bone surrounding the controls.
      The bone area density in the threads along the entire bisphosphonate screw was
      increased by 40% compared with uncoated controls, and at 250 microm distance it
      was more than doubled. At 1 week, coated screws had less implant-bone contact,
      but at 8 weeks there was no difference between uncoated and bisphosphonate-coated
      screws. The bisphosphonate screws had 50% increased removal torque at 2 weeks
      compared to uncoated screws. Howship's lacunae and osteoclasts were found near
      the screws with bisphosphonates at 8 weeks, suggesting that some bone remodeling
      took place near the implant, in spite of the presence of bisphosphonates.

PMID- 18055290
TI  - The role of ultrasound in the detection of cervical lymph node metastases in
      clinically N0 squamous cell carcinoma of the head and neck.
AB  - Nodal involvement is the most important prognostic factor in head and neck
      squamous cell carcinoma (HNSCC) of mucosal origin. The presence of a single
      ipsilateral or contralateral metastatic node reduces survival by 50% and
      bilateral disease by a further 50%. The management of N+ HNSCC is relatively
      clear-cut. By contrast, the investigation and treatment of patients with
      clinically N0 disease is controversial. Most institutions electively treat the
      neck with surgery or radiotherapy because the risk of occult metastases is over
      20%, even though it will be unnecessary in the majority of cases. In this
      situation the main purpose of staging would be to assess those nodes that are not
      going to be removed. However, the optimal management of the clinically N0 neck
      remains controversial and there is growing interest in a more conservative
      approach. Research is now directed toward finding a method of staging sensitive
      enough to bring the risk of occult metastases below 20%. High spatial resolution,
      ease of multiplanar scanning, power Doppler and the ability to perform guided
      fine-needle aspiration for cytology give ultrasound (US) an advantage over other
      imaging techniques.

PMID- 18055292
TI  - Spectrum of findings and usefulness of integrated PET/CT in patients with known
      or suspected neuroendocrine tumors of the lung.
AB  - Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) has
      been known to increase diagnostic accuracy in differentiating benign and
      malignant lung lesions and to improve identification of lymph node and
      extrathoracic metastasis in pulmonary neoplasms. In this review, the authors
      describe the spectrum of integrated PET/CT findings on neuroendocrine (NE) tumors
      of the lung. We also demonstrate the usefulness of this imaging modality in
      patients with known or suspected NE tumors of the lung.

PMID- 18055291
TI  - Radiolabeled antibodies in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is a radio- and chemotherapy resistant tumor, which
      has a very high morbidity and mortality when metastasized. The current treatment
      options demonstrate limited efficacy and severe side-effects. Therefore, there is
      a need for new therapeutic strategies for RCC. As for other malignancies,
      monoclonal antibodies (mAbs) targeting tumor-associated antigens have been
      developed for RCC. One of these, mAb G250, targets the MN/CAIX/G250 antigen,
      which is ubiquitously expressed in clear cell RCC (ccRCC). ccRCC is the most
      common form of RCC with a prevalence of 80%. Expression of G250 in normal tissue
      is restricted to the gastrointestinal mucosa and related structures, thereby
      making it a suitable candidate for targeting ccRCC. In several clinical studies
      the efficient accumulation of mAb G250 in ccRCC has been demonstrated, resulting
      in high contrast images. G250-imaging could prove to be a valuable tool in
      diagnosing metastases in patients with a G250-antigen positive primary tumor
      and/or in the differential diagnosis of suspect kidney lesions. Furthermore, the
      therapeutic efficacy of radiolabeled G250 has been investigated in a series of
      studies. Thus far, most efforts have been devoted to G250 labeled with high doses
      of 131I. Other radionuclides which may enhance the therapeutic index of this
      radiolabeled mAb are currently under investigation. In our institution, an
      activity dose escalation study is currently ongoing to investigate the
      therapeutic potential of 177Lu-labeled G250 in metastatic ccRCC patients. In this
      review, the current status of the diagnostic and therapeutic properties of
      radiolabeled antibodies in RCC is described.

PMID- 18055293
TI  - PET/CT and hepatic radiation injury in esophageal cancer patients.
AB  - This paper evaluates the imaging appearance of radiation injury in the liver on
      positron emission tomography (PET)/computed tomography (CT) in patients with
      distal esophageal cancer who underwent pre-operative chemoradiation therapy.
      Twenty-six patients with distal esophageal cancer who received chemoradiotherapy
      before esophagectomy were included. All patients had baseline and follow-up
      PET/CT. Fluorodeoxyglucose (FDG) uptake in both left and right lobes of the liver
      was evaluated. CT findings suggesting radiation damage were documented. Abnormal
      FDG uptake in the liver was observed in 5 (19%) patients after therapy. These
      abnormalities were in the left lobe (12%) and right lobe (12%) of the liver. In
      the irradiated left lobe, FDG uptake increased focally greater than 50% over
      baseline in two patients (54% and 133%); in one of these patients, biopsy
      confirmed radiation injury. In the non-irradiated right lobe, standard uptake
      values (SUV) increased diffusely in two different patients. In one patient, SUV
      decreased by at least 50% in both the right and left lobes. In the remaining
      patients, there were no significant changes in FDG uptake. Atrophy and
      attenuation changes of irradiated liver on CT were found in 15 (58%) patients. In
      patients receiving chemoradiotherapy, PET/CT may identify metabolic abnormalities
      in irradiated liver. Such abnormalities should be correlated with other imaging,
      clinical and laboratory findings to avoid confusion with hepatic metastases.

PMID- 18055294
TI  - Association of apolipoprotein E polymorphism with ischemic stroke subtypes in
      Taiwan.
AB  - The aim of this study was to clarify whether the apolipoprotein E gene (APOE) is
      related to ischemic stroke subtypes in Taiwan's Chinese population. Using the
      classification of Cerebrovascular Diseases III, 143 patients with lacunar
      infarction, 114 patients with atherothrombotic infarction, and 112 healthy
      controls were enrolled. APOE genotype was determined using polymerase chain
      reaction. Regarding the distribution of APOE genotypes, the frequency of
      epsilon3/epsilon4 genotypes in lacunar patients was significantly different from
      that in control subjects, by logistic regression, using epsilon3/epsilon3 as a
      reference group. There was no significant difference between atherothrombotic
      patients and the control group in the distribution of APOE genotypes or alleles.
      The present finding suggests that there is a probable association between
      epsilon3/epsilon4 genotype and lacunar infarcts, but not atherothrombotic
      infarcts. This indicates that genetic factors may play a role, at least
      partially, in lacunar infarction in Taiwan's Chinese population.

PMID- 18055295
TI  - Epigenetic changes in tumor suppressor genes, P15, P16, APC-3 and E-cadherin in
      body fluid.
AB  - The inactivation of tumor suppressor genes by promoter methylation plays an
      important role in the development of cancers; it can also be used as a marker to
      distinguish cancerous cells from non-cancer cells. In this study, we investigated
      the aberrant methylation profile of the tumor suppressor genes P15, P16, APC and
      E-cadherin in the cells of body fluid. A methylation-specific polymerase chain
      reaction was performed in 31 cases of malignant effusion and 39 cases of non
      malignant effusion. Aberrant promoter methylation of P15, P16, APC and E-cadherin
      genes was seen in 0%, 25.8%, 35.5% and 6.5% of malignant effusion cases,
      respectively, whereas the frequencies were 0%, 2.6%, 2.6% and 0%, respectively,
      for negative control effusion. There were statistically significant differences
      in the aberrant methylation of P16 (p = 0.008) and APC (p = 0.018) genes between
      cases of malignant effusion and controls. Methylation of one of three genes (P16,
      E-cadherin, APC) was found in 14 out of 31 (45.2%) cases of malignant effusion,
      and in two out of 39 (5.1%) cases of non-malignant effusion (p = 0.000004).
      Concurrent methylation was found in nine out of 31 (29%) cases of malignant
      effusion, but in no non-malignant effusion sample. From these results, we suggest
      that methylation-specific polymerase chain reaction to analyze the promoters of
      tumor suppressor genes can distinguish between malignant effusion and benign
      effusion, and may help cytologists to make more accurate diagnoses.

PMID- 18055296
TI  - Lightwand-guided endotracheal intubation performed by the nondominant hand is
      feasible.
AB  - The aim of this study was to evaluate the efficiency of lightwand-guided
      endotracheal intubation (LWEI) performed using either the right (dominant) or
      left (nondominant) hand. Two hundred and forty patients aged 21-64 years, with a
      Mallampati airway classification grade of I-II and undergoing endotracheal
      intubation under general anesthesia, were enrolled in this randomized and
      controlled study. Induction of anesthesia was initiated by intravenous
      administration of fentanyl (2 microg/kg) and thiopentone (5 mg/kg), and tracheal
      intubation was facilitated by intravenous atracurium (0.5 mg/kg). In the direct
      vision laryngoscope group (group D; n = 80), the intubator held the laryngoscope
      in the left hand and inserted the endotracheal tube (ETT) into the glottic
      opening with the right hand. In the group in which LWEI was performed with the
      right hand (group R; n = 80), the intubator lifted the patients' jaws with the
      left hand and inserted the ETT-LW unit into the glottic openings with the right
      hand. On the contrary, in the group in which LWEI was performed with the left
      hand (group L; n = 80), the intubator lifted the jaws with the right hand and
      inserted the ETT-LW unit with the left hand. Data including total intubation
      time, the number of intubation attempts, hemodynamic changes during intubation,
      and side effects following intubation, were collected. Regardless of whether
      lightwand manipulation was performed with the left hand (group L; 11.4 +/- 9.3 s)
      or the right-hand (group R; 12.4 +/- 9.2 s), less time was consumed in the LWEI
      groups than in the laryngoscope group (group D; 17.9 +/- 9.9 s) (p < 0.001). All
      three groups obtained success rates greater than 95% on their first intubation
      attempts. The changes in mean arterial blood pressure and heart rate were similar
      among the three groups. A higher incidence of intubation-related oral injury and
      ventricular premature contractions (VPC) was found in group D compared with
      groups L and R (oral injury: group D 8.5%, group L 1.3%, group R 0%, p = 0.005;
      VPC: group D 16.3%, group L 5%, group R 7.5%, p = 0.04). We concluded that LWEI
      performed by either dominant or nondominant hands resulted in similar efficiency,
      and could be a suitable alternative to traditional laryngoscopy. It is both
      feasible and logical for an experienced anesthesiologist to use the nondominant
      hand to perform LWEI.

PMID- 18055297
TI  - Management of poisonous snake bites in southern Taiwan.
AB  - Snake bite envenomation is not uncommon in Taiwan. This study focuses on the
      pattern of poisonous snake bites and their management in southern Taiwan over a 5
      year period. The case histories of 37 patients with poisonous snake bites
      admitted to the Kaohsiung Medical University Hospital between June 2001 and July
      2005 were analyzed retrospectively. Three patients, bitten by unknown species of
      venomous snakes, were excluded from this study. The frequency of snakebites from
      each species of snake, the local and systemic manifestations of snake bite,
      treatment of complications and final outcomes were analyzed. Of the remaining 34
      patients, 11 (32.4%) were bitten by bamboo vipers, 10 (29.4%) by Russell's pit
      vipers, 8 (23.5%) by Taiwan cobras and 5 (14.7%) by Taiwan Habu. The majority of
      snake bites (28) occurred between May and November. Those affected were mainly
      outdoor hikers (14) and workers (9). The antivenin requirements for treatment in
      the emergency room were in accordance with standard procedures. No mortality was
      noted among those envenomed by poisonous snakes. Although poisonous snake bite is
      not a common life-threatening emergency in the study area, we observed both an
      environmental risk and a seasonal incidence of snake bite. Keeping the varied
      clinical manifestations of snake bite in mind is important for effective
      management. Ready availability and appropriate use of antivenin, close monitoring
      of patients, institution of ventilatory support and early referral to a larger
      hospital when required, all help reduce mortality.

PMID- 18055298
TI  - Three-dimensional relationship of the maxillary anterior teeth to the incisive
      papilla in young adults.
AB  - The use of the incisive papilla as an important guide for setting maxillary teeth
      has been applied in prosthetic dentistry. The purpose of this study was to
      estimate the relationship between maxillary anterior teeth and the incisive
      papilla of young adults with approximately optimal occlusion in Taiwan. Study
      casts of 100 young adults (50 males, 50 females; mean age, 22.4 years) were
      selected in this study. All of the marked points on maxillary casts were measured
      using a three-dimensional precise measuring device. The relative positions of
      maxillary teeth landmarks to incisive papilla were measured and analyzed using
      SAS software (JMP 4.02). Student's t test and Pearson's correlation test were
      used to test the statistical significance of any differences (p < 0.05). The
      results showed that the mesiolabial incisal edge of the upper central incisor was
      7.30 +/- 0.64 mm anterior to the center of the incisive papilla. There was no
      significant difference in gender (p > 0.05). The intercanine line was 0.27 +/-
      1.30 mm posterior to the center of incisive papilla. There was no significant
      difference in gender (p > 0.05). The horizontal distances of the mesiolabial
      incisal edge of the upper central incisor and the intercanine line to the center
      of the incisive papilla showed only weak correlation (r < 0.5). In addition, the
      three-dimensional relationship of maxillary anterior teeth to the center of the
      incisive papilla was measured and analyzed. We suggest using the incisive papilla
      as a reference landmark for the setting of maxillary anterior teeth.

PMID- 18055299
TI  - Insulinoma-associated transient hypothalamus-pituitary-adrenal axis impairment
      and amelioration by steroid therapy and surgical intervention: a case report.
AB  - Insulinoma is the most common functional tumor among pancreatic islet cell
      tumors. This type of tumor is difficult to localize prior to surgery and can lead
      to serious hypoglycemia. This paper presents the case of a young female who
      suffered from insulinoma associated with transient hypothalamus-pituitary-adrenal
      axis impairment. To localize her insulinoma, we used two alternative testing
      methods, somatostatin receptor scintigraphy and selective arterial calcium
      stimulation with venous sampling, after a failure of conventional imaging
      methods. We treated her adrenal insufficiency and prevented serious hypoglycemia
      by giving her prednisolone. The impairment in her hypothalamus-pituitary-adrenal
      axis and her serious hypoglycemia recovered after excision of the tumor.

PMID- 18055300
TI  - The Winter procedure as management for prolonged low-flow priapism: a case
      report.
AB  - Priapism is a prolonged penile erection that is not associated with sexual
      stimulation. Although the time course has not been formally defined, it is
      usually considered to be one that lasts for more than 4-6 hours. Low-flow
      (ischemic) priapism is usually associated with sickle cell disease,
      hemoglobinopathies, neoplastic syndrome, anticoagulant therapy, psychotropic
      medication or idiopathic causes. Here, we report a case of prolonged low-flow
      priapism lasting for 2 weeks, which was successfully treated with the Winter
      procedure after several attempts of conservative treatment. Although the potency
      remains unclear and the patient needs a longer period of follow-up, the case
      reported here still shows that prolonged low-flow priapism can be successfully
      treated with the Winter procedure when conservative treatments fail.

PMID- 18055301
TI  - Reconstruction of the soft palate in oral cancer to repair an operative defect
      with speech aid prosthesis: a case report.
AB  - A soft palate defect may result from surgical resection, and its consequences
      could include hypernasal speech and nasal regurgitation of food and liquids. A
      speech aid prosthesis fabricated for patients can improve nasal emission during
      speech, and assist in preventing nasal regurgitation of food. This article
      presents a case of the reconstruction of a soft palate defect by prosthetic
      obturation.

PMID- 18055302
TI  - Evaluating the validity of the serologic test for detecting Helicobacter pylori
      infection in Mongolian gerbils.
AB  - A strong correlation between Helicobacter pylori infection and gastric cancer has
      been reported. Mongolian gerbils are regarded as the most suitable animal model
      in which to study carcinogenesis associated with H. pylori. The aim of our study
      was to evaluate the accuracy of the serologic test for detecting H. pylori
      infection in Mongolian gerbils. The model was developed as follows: the H. pylori
      colony (vacuolating cytotoxin A (+)/cytotoxin-associated gene A (+)) was cultured
      from the mucosas of previously H. pylori-fed gerbils. These colonies were
      cultured in broth. Then,we fed the gerbils with 0.5-1 mL of broth (about 10(9)
      CFU/mL) (intragastric administration) twice within a 3-day period. After
      inoculation for 6 or 26 weeks, the gerbils were sacrificed and their gastric
      mucosas were sampled for a series of examinations. Blood samples for serologic
      testing (STAT-PAK) were collected. H. pylori infection was confirmed. Statistical
      analysis was performed using the Chi-square test. Differences were regarded as
      significant when the p value was less than 0.05. A total of 50 gerbils were
      inoculated with H. pylori and the success rate reached 88%. All 10 gerbils in the
      control group showed a negative result. Damage to the mucosas was more obvious
      following increasing periods of inoculation. The rates of sensitivity and
      specificity, as determined by the STAT-PAK test, were 90.9% and 100%,
      respectively. The positive and negative predictive values were 100% and 60%,
      respectively. The STAT-PAK test seemed to be more sensitive and accurate (p <
      0.05) in high H. pylori densities. In conclusion, the STAT-PAK test (blood
      sampling) showed acceptable results and was suitable for long-term observation of
      H. pylori infection.

PMID- 18055303
TI  - Pre-hospital and in-hospital delays after onset of acute ischemic stroke: a
      hospital-based study in southern Taiwan.
AB  - The biggest hurdle for early hospital presentation is the narrow therapeutic
      window after stroke. The aims of our study were to investigate the time lags and
      the factors causing pre-hospital and emergency department (ED) delay during acute
      ischemic stroke attack. Between June 2004 and October 2005, we prospectively
      studied 129 acute ischemic stroke patients who presented to the ED of the study
      hospital within 4 hours after symptom onset. Chi-square testing for trend,
      univariate and multiple logistic regression analyses was performed to evaluate
      the factors influencing delays in the ED presentation of acute ischemic stroke
      patients. The median time from symptom onset to ED arrival was 71 (mean +/- SD,
      82.7 +/- 57.7) minutes. The median times from ED arrival to neurologic
      consultation, computed tomography scan, electrocardiogram, and laboratory data
      completion were 10 (11.3 +/- 9.9) minutes, 17 (9.6 +/- 11.3) minutes, 14 (23.3 +/
      55) minutes, and 39 (44.4 +/- 24.5) minutes, respectively. Univariate and
      multiple logistic regression models revealed that age < 65 years, illiteracy and
      awakening with symptoms were the most significant factors related to a delay in
      ED presentation. This study indicates that 2 hours of pre-hospital delay is the
      cutoff point for thrombolytic therapy. Organization of a stroke team and
      standardized stroke pathways may help to shorten in-hospital time consumption.
      Educational efforts should not only focus on the public, but also on the training
      of ED physicians and other medical personnel.

PMID- 18055304
TI  - Neuropeptide Y gene polymorphism and plasma neuropeptide Y level in febrile
      seizure patients in Taiwan.
AB  - Neuropeptide Y (NPY) has been shown to depress the hyperexcitability of neurons.
      In the present study, we investigated the association between the nucleotide (nt)
      5671 C/T polymorphism of the NPY gene and the plasma NPY level in patients with
      febrile seizures (FS). Fifty-six patients with FS and 55 control subjects were
      enrolled. Genotype and allele frequencies were compared. The frequencies of
      genotypes TT, TC and CC for the NPY gene nt 5671 C/T polymorphism were 21.4%,
      28.6% and 50.0%, respectively, in patients with FS, and 14.6%, 40.0% and 45.4%,
      respectively, in control subjects. The frequencies of alleles T and C were 35.7%
      and 64.3%, respectively, in patients with FS, while those in the control group
      were 34.5% and 65.5%, respectively. We found no significant relationship between
      the NPY gene nt 5671 C/T polymorphism and FS. The plasma NPY concentrations of
      the FS group, the age-matched non-FS group, and subjects aged > 6 years in the
      non-FS group were 48.23 +/- 32.49, 55.36 +/- 23.12, and 70.10 +/- 60.31 pg/mL,
      respectively. These results indicate no statistical difference in plasma NPY
      concentration between FS patients and the non-FS group. However, plasma NPY
      concentration was found to increase significantly with age.

PMID- 18055305
TI  - Clinical experience of a microvascular venous coupler device in free tissue
      transfers.
AB  - Most free flap failures result from technical problems in performing vascular
      anastomoses, such as endothelial intima lacerations, distortion of the vessels,
      and unequal intersuture distances. These incorrect practices can lead to
      thrombosis formation and, ultimately, flap failure. Solving this problem is a
      challenging issue for all micro-reconstructive surgeons. In the last decade, a
      vascular anastomotic coupler instrument was developed and reported on. We review
      our recent experiences of free tissue transfer using this vascular coupler
      device, and discuss how venous problems can be overcome with its aid. We believe
      the excellent patency rate of the coupler may minimize the well-described
      problems of venous thrombosis in the challenging field of free tissue
      reconstructions.

PMID- 18055306
TI  - Analysis of surgically treated intraspinal tumors in southern Taiwan.
AB  - The medical records of 117 patients with spinal tumors who underwent surgery with
      pathologic confirmation from January 1999 to April 2004 at Kaohsiung Medical
      University Hospital were reviewed. Data from this review were compared with those
      obtained from the same institution 10 years earlier (covering the period 1988
      1995) and from other reported series. There were 69 male and 48 female patients
      aged from 13 to 87 years old (mean age, 51.9). The most common pathologic
      findings were metastasis in 45.3% (53/117), nerve sheath tumors in 28.2%
      (33/117), meningiomas in 12% (14/117) and neuroepithelial tumors in 6% (7/117).
      The peak ages at diagnosis were 41-50 years and 61-70 years. A slight male
      predominance was noted for all tumors, except meningiomas. Motor weakness, even
      paralysis, was the major clinical presentation (64-86%), followed by sensory
      deficits (50%) and pain (42%). The location of tumors was most often in the
      thoracic (50.4%; 59/117), lumbosacral (27.4%; 32/117) and cervical spine (22.2%;
      26/117) segments. Among the metastatic tumors, the lung (22.6%) and breast
      (15.1%) were the most common primary sites of origin, followed by unknown origin,
      the liver (hepatocellular carcinoma), the gastrointestinal tract and the
      nasopharynx (nasopharyngeal cancer).

PMID- 18055307
TI  - Recurrent acute renal failure in a patient with aplastic anemia-paroxysmal
      nocturnal hemoglobinuria syndrome: a case report.
AB  - Acute renal failure (ARF) is one of the renal expressions in patients with
      aplastic anemia (AA)-paroxysmal nocturnal hemoglobinuria (PNH) syndrome following
      hemolytic crisis. We report the case of an AA patient who experienced recurrent
      episodes of ARF, in association with evidence of PNH. A 46-year-old woman with AA
      was admitted because of oliguria and dark urine following a urinary tract
      infection (UTI) caused by Candida. PNH with ARF complication was diagnosed.
      Hemodialysis treatment was performed nine times and her renal function recovered.
      However, she suffered from recurrent hemoglobinuria and acute deterioration of
      renal function 4 months later. The renal biopsy showed features of acute tubular
      necrosis, deposition of hemosiderin and positive urate stain in the proximal
      tubular cells, without vascular thrombosis. The patient received management by
      adequate hydration, diuretics and alkalization. Her renal function recovered
      completely. This case report shows an AA patient experiencing recurrent episodes
      of hemoglobinuric ARF within a short period and achieving complete recovery of
      renal function after hemodialysis and suitable supportive treatment. In
      conclusion, AA might evolve into PNH and become complicated with presentation of
      severe ARF. It may occur with precipitating episodes, such as the UTI in this
      case. Early recognition of hemoglobinuric complications and prompt treatment for
      precipitating disease and ARF are important to prevent progression to an
      irreversible adverse renal outcome.

PMID- 18055308
TI  - Adult Wilms' tumor with hypospadias and cryptorchidism: a case report.
AB  - A 66-year-old patient was seen at the outpatient department with the chief
      complaints of recent-onset painless gross hematuria, poor appetite and body
      weight loss. The patient had a history of bilateral orchiectomy for congenital
      bilateral cryptorchidism. Hypospadias was noted during physical examination.
      Laboratory assessment revealed hematuria and pyuria. Abdominal ultrasonography
      and imaging studies showed a left renal mass. Radical nephrectomy was performed
      on the patient and the pathology report revealed Wilms' tumor (nephroblastoma).
      The patient underwent chemotherapy after surgery and no tumor recurrence was
      noted after 8 months of regular follow-up.

PMID- 18055309
TI  - Sublingual gland sialolithiasis: a case report.
AB  - Sublingual gland sialolithiasis is rare and may be misdiagnosed as submandibular
      gland sialolithiasis, which is more common. It is important to preoperatively
      determine which gland is involved, because they require different surgical
      approaches. Computed tomography (CT) is useful for distinguishing between
      sublingual gland and submandibular gland sialolithiasis. In this paper, we report
      the case of a 50-year-old man with left sublingual gland sialolithiasis that was
      treated with excision of the left sublingual gland and the stone via a transoral
      approach, 6 weeks after the infection was controlled. The differential diagnosis
      between sublingual gland and submandibular gland sialolithiases, by use of CT
      images, is discussed from an anatomic viewpoint.

PMID- 18055310
TI  - Switching from branded to generic antiepileptic drugs as a confounding factor and
      unpredictable diagnostic pitfall in epilepsy management.

PMID- 18055311
TI  - [Phase I cancer trials methodology].
AB  - The main objective of phase I cancer trials is to determine precisely the
      recommended dose of an anticancer agent as a single agent or in a context of
      combinations of anticancer agents (including cytotoxic agents, immunotherapy,
      radiotherapy...), that is administered for the first time in man, to further
      proceed clinical development with phase II and III trials. The recommended dose
      must have the greatest efficiency with acceptable toxicity. For the anticancer
      agents, the ratio risk/benefit is high, since toxicities associated with many
      cancer therapeutic agents are substantial and because the efficacy is often
      limited. Thus, phase I cancer trials present unique challenges in comparison to
      other therapeutic areas. Indeed, it is essential to minimize the numbers of
      patients treated at subefficient dose levels, and in the same time not to expose
      the patients to unacceptable toxicity. Historically, the first method that has
      been used is the Fibonacci escalation. The major problems raised with this method
      have been the lengths of the trials and the risk to treat substantial numbers of
      patients at nontherapeutix doses. Thus, novel methods have been then developed
      modifying the numbers of patients included at each dose level and the rapidity of
      dose escalation. These methods include pharmacologically guided dose escalation,
      escalation with overdose control and the continual reassessment method which are
      both statistically based dose escalation methods, and the accelerated titration
      designs. Concerning the targeted anticancer therapies, the therapeutic effect on
      the target, due to their higher specificity, can be obtained using doses that
      have few toxicity. Using the toxicity to determine the recommended dose for phase
      II trials, as it is the case for "classical >> anticancer agents, does not seem
      to be sufficient. Alternatives to determine the optimal biological dose include
      measurement of target inhibition, pharmacokinetic analysis and functional
      imaging.

PMID- 18055312
TI  - [Randomised phase II trials in oncology].
AB  - The purpose of phase II trials is to identify signals in favor of the efficacy of
      a drug in development. The main pitfall of a phase II study is to conclude by
      error that a drug has no activity, leading to a stop in the development of a drug
      which has a real efficacy. In oncology, more and more phase II trials are
      randomised, even though there are still numerous non randomised studies.
      Randomisation allows some control on the risk of patient selection bias, inherent
      to non randomised trials. This bias consists of recruiting by chance a population
      of patients with high risk or on the contrary low risk of response to the
      experimental treatment. The present paper describes the various types of
      randomised phase II trials, their principles, strengths and limits.

PMID- 18055313
TI  - [Meta-analyses on individual patient data and treatment evaluation in oncology].
AB  - A meta-analysis of trials addressing the same question is a quantitative
      synthesis of their results. Such a synthesis is useful when the overall result of
      these trials does not produce a clear answer. In oncology, the moderate effect of
      most available treatments explains the widespread use of meta-analyses. They are
      one of the way to reach a sufficient power. A meta-analysis provides a test for
      the efficacy of the treatment under study, and an estimation of this efficacy. To
      perform a meta-analysis, one must identify all the randomised trials addressing
      the question, whether their results have been published or not. The quality of a
      meta-analysis depends largely on the completeness of the collection of trials. A
      meta-analysis can be based on summary data or it can be based on individual
      patient data which allows intensive data checking, data corrections and update,
      and an intent to treat analysis. Individual patient data meta-analysis is the
      reference method. It is particularly useful for controversial questions, or when
      a small benefit is expected or when long-term follow-up is important, all these
      situations being frequent in oncology. It allows extensive analyses, for instance
      the study of the variation in treatment effect according to patient's and trials
      characteristics. Detailed verification of the data are essential since the
      inclusion of ill designed and ill conducted trials can only lead to a bad meta
      analysis. Close collaboration with investigators is needed in this type of meta
      analysis leading to large and rapid diffusion of the results. Meta-analyses and
      large-scale trials are complementary tools for treatment evaluation in oncology.
      Lastly, the large data bases of individual patient data meta-analyses allow
      subsidiary studies such as validation studies of surrogate endpoints or studies
      of the predictive value of tumour markers.

PMID- 18055314
TI  - [Interim analyses].
AB  - The methodological principles for the planning of interim analyses in a phase III
      clinical trial are presented in this article. The case for superiority, non
      inferiority and futility, and the roles of Data Monitoring Committees are
      summarized. Several examples are presented to illustrate the methodology and to
      help investigators by better understanding and planning interim analyses in a
      phase III clinical trial.

PMID- 18055315
TI  - [Gene expression profiling in cancer research].
AB  - Gene expression profiling is increasingly used in cancer research. For each
      patient, the expression of thousands of genes in the tumour can be measured
      simultaneously on a microarray. Microarray studies aim at classifying patients
      based on two types of classification schemes: unsupervised classification, which
      uses clustering in order to identify homogeneous subtypes of a disease on the
      basis of gene expression, or supervised classification, which principally aims at
      the identification of genes or set of genes differentially expressed between
      tumours with different characteristics (molecular signature), for instance
      between a group of patients with bad and good prognosis. The data consists of a
      small number of patients and a large number of variables, raising serious
      methodological problems. We will use published results on breast cancer in order
      both to study the power of the experiments and to illustrate the problems in
      interpretation and validity of their results. We recommend rigorous evaluation of
      this new technology.

PMID- 18055316
TI  - [Angiogenesis inhibitor therapies: focus on hypertension and kidney toxicity].
AB  - Developments in the knowledge of molecular biology of cancer over the past 20
      years have been identified. Angiogenesis is playing a key role in the
      physiopathology of cancer evolution. Several strategies have been developed to
      target angiogenesis for the treatment of metastatic RCC. These include inhibition
      of VEGF receptors (inhibition of the tyrosine kinase activity) or binding to the
      VEGF protein. Several additional kinases inhibitions including PDGF receptors are
      also targeted. Anti-angiogenic drugs recently marketed or still under clinical
      development, may interact with the kidneys. Clinical and pathological, and
      mechanisms of their renal toxicity are presented in this article.

PMID- 18055317
TI  - [Craniopharyngiomas: role of radiotherapy].
AB  - Craniopharyngiomas are benign tumors of the parasellar region, characterised by
      high relapsing rate. Aggressive attempt at total removal does result in prolonged
      progression-free survival in most patients. But for tumors that clearly involve
      the hypothalamus, complications associated with radical surgery have prompted to
      adopt a combined strategy of conservative surgery and radiation therapy to
      residual tumor with an as high rate of cure. This strategy seems to offer the
      best long-term control rates with acceptable morbidity. But optimal management of
      craniopharyngiomas remains controversial. Although it is generally recommended
      that radiotherapy is given following sub-total excision of a craniopharyngioma,
      it remains unclear as to whether all patients with residual tumour should receive
      immediate or differed at relapse radiotherapy.

PMID- 18055318
TI  - [Comparison of different approaches in surgical management of early endometrial
      cancer].
AB  - The objective is to assess the feasibility of laparoscopy in the treatment of
      endometrial carcinoma and to compare operating data and morbidity to laparotomy.
      Retrospective review of 70 consecutive patients with supposed early endometrial
      cancer managed between December 2000 and December 2005. Two groups were defined,
      whether they had been operated by laparoscopy (N = 44 ; LPS group) or by
      laparotomy (N = 21 ; LPM group). Both groups were comparable in mean age and body
      mass index. There was no significant difference in median operating time for LPS
      group (240 minutes [90-390]) and LPM group (195 minutes [120-600]), (p = 0.234).
      Intraoperative complications occurred in 2 LPS patients (4.7 %) and in 2 LPM
      cases (9.5 %). Women who underwent laparoscopy had more pelvic lymph nodes
      removed (11.5 [2-33] versus 7.5 [3-37], p < 0.05). There were comparable early
      and late postoperative complications in patients managed by laparoscopy (5 and 0
      cases ; 27.8 and 0 %) and by laparotomy (5 and 2 cases ; 11.6 and 4.5 %), (p =
      0.143 and p > 0.999). Hospital stay was longer in LPM group (9.5 days [6-39]
      versus 5.0 (4-27), p < 0.05). Patients who undergo laparoscopy have more pelvic
      lymph nodes removed, with comparable operating time, shorter hospital stay, and
      similar morbidity. Laparoscopic staging combined with vaginal hysterectomy
      appears to be a feasible alternative to conventional surgical approach in
      patients with endometrial carcinoma.

PMID- 18055319
TI  - [Clinical effects of new technologies in medical imagery: the example of breast
      screening].
AB  - In the frame of cancer screening, we present a new psychological concept
      elaborated from our clinical practice of women affected by a breast cancer. The
      experience of these women is different depending on whether the cancer is
      discovered in an asymptomatic context or not. We introduce the concept of
      "anticipatrice medicine" in order to define the implication of diagnosis
      precocity on the therapeutic strategy, because of a modification of some main
      parameters which make up the ordinary personal concept. These parameters are :
      the time in which disease anticipates the symptom and the space where the
      treatment anticipates the disease. We discuss the paradoxical experience of
      screening which imposes a medical intervention before any symptom that is for the
      patient to be treated before any feeling of the disease, and to experience the
      disease through the experience of a treatment. The different elements of this
      paradoxical experience are successively identified and analysed. Finally we
      propose four directions of research in the field of interaction between human and
      medical technologies.

PMID- 18055320
TI  - [Use of complementary medicine by cancer patients in a French oncology
      department].
AB  - The aims of this study was to estimate and describe the reasons of use of
      complementary medicine in patients with a cancer treated in a French oncology
      department. An anonymous questionnaire was proposed to patients during treatment
      or follow-up in an oncology department. It was a descriptive study over 207
      questionnaires. Over 195 analysable questionnaires, 34% of patients were using
      complementary medicine. Homeopathy (42%), plants (27%) and vitamins (18%) were
      the main substances used. Acupuncture (22%) and massages (15%) were the most
      significant techniques. No specific profile of user was observed. The main reason
      of using complementary medicine was not curing cancer but reducing side effects
      of the conventional treatment (66%). More than a half of the users of
      complementary medicine were not revealing their habits to their oncologist
      because the question was not raised in consultation. One third of cancer patients
      are using complementary medicine during the treatment of their disease.
      Complementary medicine must benefit, as well as conventional medicine, of
      scientific studies. The purpose of these studies should be evaluating potential
      benefits, toxicity and interactions with the conventional treatment in order the
      oncologist could warned the users. This warning could improve the confidence
      relationship between the oncologist and his patient.

PMID- 18055321
TI  - Cancer treatment and fertility: a time to reassess realistic opportunities.

PMID- 18055322
TI  - Global strategy against cancer in the society of information.

PMID- 18055323
TI  - Molecular biology of thyroid cancer initiation.
AB  - Thyroid cancers stand out among solid tumours because many of the tumour
      initiating genetic events have been identified. Mutations leading to constitutive
      activation of MAP kinase effectors -the tyrosine receptor kinase RET and the
      intracellular signalling effectors RAS and BRAF- are essential for the
      pathogenesis of papillary thyroid carcinoma (PTC). Similarly, there is increasing
      evidence demonstrating that mutations leading to activation of the
      phosphatidylinositol 3- kinase (PI3K)/AKT effectors -PTEN and PI3KCa- are
      essential for the pathogenesis of follicular thyroid carcinoma (FTC). Besides
      this strong relationship between the histological phenotype and the pathway
      predominantly activated, the nature of the genetic event seems to determine the
      biological behaviour of the tumour and the ultimate clinical outcome of the
      patient. In this review we will summarise and discuss the main genetic events
      related to thyroid cancer initiation, the contribution of genomics and the
      convenience of using a new molecular classification of thyroid cancer,
      complementary to the clinicopathological classification. This may help us to
      predict more faithfully the clinical outcome of patients with thyroid cancer and
      to select more appropriately candidates for targeted therapies.

PMID- 18055324
TI  - Cyclooxygenase-2 (COX-2): a molecular target in prostate cancer.
AB  - Epidemiological studies provided the first evidence that COX may be involved in
      the pathogenesis of cancer. In the process of carcinogenesis and in the route of
      intracellular signalling during carcinogenesis, COX-2 expression may be a
      universal phenomenon. In general, COX-2 is up-regulated throughout the
      tumorigenic process, from early hyperplasia to metastatic disease. COX-2 has been
      reported to be constitutively overexpressed in a variety of malignancies and is
      frequently constitutively elevated in prostate carcinoma. COX-2 was consistently
      overexpressed in premalignant lesions such as prostatic intraepithelial
      neoplasia, and carcinoma. Cases are described with evolution of proliferative
      inflammatory atrophy of the prostate and prostate carcinoma. The increase of
      evidence implicating COX-2 in cancer has stimulated clinical trials to
      investigate the efficacy of selective COX-2 inhibitors in individuals at risk for
      human cancer. Regarding prostate carcinoma there is much direct or indirect
      evidence to support the use of COX-2 inhibitors in this disease. Trials using
      these drugs in familial adenomatous polyposis (FAP) and other patients with a
      high risk of colorectal carcinoma are ongoing.

PMID- 18055325
TI  - Non-invasive genetic imaging for molecular and cell therapies of cancer.
AB  - Gene therapy is a very attractive strategy in experimental cancer therapy.
      Ideally, the approach aims to deliver therapeutic genes selectively to cancer
      cells. However, progress in the improvement of gene therapy formulations has been
      hampered by difficulties in measuring transgene delivery and in quantifying
      transgene expression in vivo. In clinical trials, endpoints rely almost
      exclusively on the analysis of biopsies, which provide limited information. Non
      invasive monitoring of gene delivery and expression is a very attractive approach
      as it can be repeated over time in the same patient to provide spatiotemporal
      information on gene expression on a whole body scale. Thus, imaging methods can
      uniquely provide researchers and clinicians the ability to directly and serially
      assess morphological, functional and metabolic changes consequent to molecular
      and cellular based therapies. This review highlights the various methods
      currently being developed in preclinical models.

PMID- 18055326
TI  - Erythropoietin pharmacology.
AB  - Anaemia is a frequent complication in cancer patients and may be multifactorial
      in origin. Treatment with recombinant human erythropoietin (rHuEPO) is an
      alternative to red blood cell transfusion. The evidence from clinical trials has
      established that patients with chemotherapy-induced anaemia with a haemoglobin
      concentration below 10 g/dl benefit from epoetin therapy. The native glycoprotein
      hormone consists of 165 amino acids with three N-glycosylation and one O
      glycosylation sites. Epoetin and darbepoetin bind to the EPO receptor to induce
      intracellular signalling by the same intracellular molecules as native EPO. There
      are some differences in the glycosylation pattern which lead to variations in the
      pharmacokinetics and pharmacodynamics profiles. Pharmacokinetic and therapeutic
      studies have examined the use of rHuEPO administered intravenously and
      subcutaneously and there is accumulating evidence that the latter route has
      several advantages in cancer patients. After subcutaneous administration, the
      bioavailability of epoetin is about 20-30% and has a plasma half-life of >24 h.
      Darbepoetin has a longer half-life after subcutaneous administration of 48 h. The
      general recommendations are based on evidence from trials in which epoetin was
      administered 150 U/kg thrice weekly. The recommended initial dose for darbepoetin
      alpha is 2.25 mug/kg per week. The most serious adverse effects are hypertension,
      bleeding and increased risk of thrombotic complications. Caution is advised when
      used in patients who are at high risk for thromboembolic events. In the
      management of anaemic cancer patients, physicians should closely follow the
      National Comprehensive Cancer Network (NCCN) and American Society of Clinical
      Oncology (ASCO)/American Society of Hematology (ASH) guidelines.

PMID- 18055327
TI  - Guidelines for the detection and treatment of liver metastases of colorectal
      cancer.
AB  - The spread of the surgical treatment for hepatic metastases have been crucial in
      the improvement of treatment and survival of metastatic colorectal cancer. The
      early and accurate diagnosis of metastases and the assessment of their size are
      essential factors to reach the optimal results with this treatment strategy. The
      precise indication of the surgical technique with or without the previous
      administration of neoadjuvant chemotherapy is of significant importance for the
      choice of R0 surgery and the timing of intervention. Although there is an
      agreement regarding some parameters related to diagnosis techniques and surgical
      criteria such as the bilobar extension, the size of the remaining liver post
      surgical removal and the indication of pre-operatory chemotherapy, it is
      necessary to consider all these factors to set up standard criteria and optimize
      the results. In this article we review all these parameters, from disease follow
      up to detect metastatic dissemination to the basic criteria for use of
      neoadjuvant chemotherapy, in order to suggest some general recommendations of
      evidence level II and recommendation grade A.

PMID- 18055329
TI  - Pseudomyxoma peritonei secondary to epithelial appendicular neoplasms. Experience
      in a non-specialised centre.
AB  - INTRODUCTION: Pseudomyxoma peritonei is an infrequent entity, defined by
      collections of gelatinous material in the abdomen and pelvis and mucinous
      implants on peritoneum, secondary to the rupture of a mucinous lesion, usually of
      ovarian or appendiceal origin. MATERIALS AND METHODS: We present our experience
      of 11 cases (6 males and 5 females) diagnosed with pseudomyxoma peritonei
      secondary to epithelial appendicular neoplasms over 27 years. The mean age of the
      patients was 68 years. Clinical manifestations were abdominal distension (55%),
      right lower quadrant pain (45%) suggesting acute appendicitis and constitutional
      syndrome (36%). An abdominal mass was detected at physical examination in 4
      patients. CT scan revealed a tumour in right iliac fossa in 4 patients,
      peritoneal enlargement in 1 and a liquid collection in 1. Preoperative diagnosis
      was acute abdomen in 5 patients, peritoneal carcinomatosis in 3 and undetermined
      abdominal mass in 3. RESULTS: Surgical findings suggested pseudomyxoma peritonei
      in 8 patients and peritoneal carcinomatosis in 3. Appendicectomy was performed in
      9 patients, and in 3 of them bilateral anexectomy was also performed. One patient
      underwent ileocaecal resection and another a right hemicolectomy. In all the
      cases, mucinous material was eliminated as much as possible. Pathology revealed
      mucinous cystoadenoma in 6 cases, mucinous cystoadenocarcinoma in 3 and
      epithelial hyperplasia in 2 patients. Median survival was 54 months, with a 5-
      year survival rate of 40%. The last case we treated was sent to a reference
      centre for the treatment of pseudomyxoma peritonei. CONCLUSIONS: There is no
      consensus on the best treatment for pseudomyxoma peritonei. We recommend avoiding
      incomplete surgical resections in non-reference centres and submitting patients
      to a reference centre to undergo adequate treatment.

PMID- 18055328
TI  - Detection of survivin mRNA in urine of patients with superficial urothelial cell
      carcinomas.
AB  - INTRODUCTION: The aim of the present study was to assess if the presence of
      survivin mRNA in exfoliated cells present in urine samples can be a reliable
      marker of the presence of bladder tumour and recurrence. MATERIALS AND METHODS:
      Urine samples from 30 patients with superficial urothelial cell carcinomas (UCC)
      were collected prior to transurethral resection (TUR) of the tumour and in the
      first routine follow-up, three months after TUR. Detection of survivin mRNA was
      performed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:
      No correlation was observed between survivin detection and the
      clinicopathological variables analysed, nevertheless, when patients were grouped
      into low-grade (G1) and high-grade (G2+G3) tumours, statistically significant
      differences were found between both groups (p=0.04). When we analysed the results
      of survivin detection and urinary cytology together, we observed that informative
      cases rose from 27.8% to 44.4%. Also, Kaplan-Meier curves for patients with
      negative cytology in the first followup, categorised according to survivin
      detection, revealed that survivin mRNA positive cases recurred earlier than
      negative ones. CONCLUSIONS: From our results we can conclude that detection of
      survivin expression can be a reliable tumour marker, but more studies are needed
      to clarify the potential of survivin to predict recurrences. These results showed
      that survivin detection in combination with conventional urinary cytology can be
      a useful tool to increase the sensitivity in detecting the presence of a
      recurrence after TUR.

PMID- 18055330
TI  - Brain metastases as the first sign of colon cancer.
AB  - Cerebral metastases from colorectal cancer occur in 8% of cases. Diagnosis is
      usually made when primary disease and widespread metastases are already known.
      However, the detection of brain metastases as the first sign of colorectal
      carcinoma without any liver and/or lung involvement is extremely rare. Central
      nervous system metastases are more commonly seen in rectal cancer and often occur
      concurrently with lung metastasis. We report a case of a patient with brain
      metastases as the first clinical manifestation of an adenocarcinoma of caecum
      without any other organ involvement.

PMID- 18055331
TI  - Nonbacterial thrombotic endocarditis associated with lung adenocarcinoma.
AB  - Nonbacterial thrombotic endocarditis (NBTE) is a rather frequent neoplasic
      complication, most often occurring in adenocarcinomas of the lung and pancreas.
      The most frequent clinical manifestation is one of multiple cerebral infarcts,
      but other ischaemic events can occur. Diagnosis is frequently missed on
      transthoracic ultrasound, making transoesophagic ultrasound a more reliable
      diagnostic tool. We present a case of NBTE associated with lung adenocarcinoma.

PMID- 18055332
TI  - An outcome-based action study on changes in fitness, blood lipids, and exercise
      adherence, using the disconnected values (intervention) model.
AB  - The authors' purpose in this action study was to examine the effect of a 10-week
      intervention, using the Disconnected Values Model (DVM), on changes in selected
      measures of fitness, blood lipids, and exercise adherence among 51 university
      faculty (10 men and 41 women) from a school in the southeastern United States.
      The DVM is an intervention model that is intended to provide incentive to replace
      unhealthy with healthy behavioral patterns. Multivariate Mixed Model analyses
      indicated significantly improved fitness (ie, cardiovascular, strength, percent
      body fat) and lipid profile (eg, blood cholesterol, triglycerides) scores between
      pre- and postintervention on all measures (ps < .05) with the exception of blood
      pressure and high-density lipoprotein cholesterol (ps > .05). Adherence for
      cardiovascular activity averaged 22 out of 30 sessions (73%), and strength
      training adherence averaged 13 out of 20 sessions (65%). The results of this
      outcome-based study suggest that the DVM provides an effective cognitive
      behavioral approach to promoting regular exercise.

PMID- 18055333
TI  - Evaluation of the effectiveness of biobehavioral therapy in the treatment of
      temporomandibular disorders: a literature review.
AB  - Temporomandibular disorders (TMDs) involve a heterogeneous group of clinical
      conditions affecting the stomatognathic system and its related structures.
      Because the etiology of these disorders is still unclear, a wide range of
      therapeutic solutions has been proposed in the literature, including occlusal
      appliances, physical therapies, drugs, and biobehavioral modalities.
      Biobehavioral therapy could have a beneficial effect in the treatment of TMDs
      because of the reportedly high prevalence of psychological dysfunction in TMD
      patients. The authors reviewed the biobehavioral modalities used to achieve pain
      relief in patients affected by such disorders, with the aim of synthesizing data
      on the effectiveness these therapeutic approaches. Literature data suggest that
      the inclusion of biobehavioral interventions in the management of TMDs may be
      reasonable, even if no conclusions can be drawn about their long-term
      effectiveness.

PMID- 18055334
TI  - Evolving new treatment for myelodysplastic syndromes.
AB  - Over the last several years, there has been substantial progress in the
      definition, diagnosis, and management of myelodysplastic syndromes (MDSs). This
      progress includes the new World Health Organization classification and the
      revised standardized response criteria to be applicable to most new compounds,
      which, taken together with the International Prognostic Scoring System, provide a
      uniform basis for the management of individual patients. The recent introduction
      of certain new agents, as well as an apparent increase in the use of stem cell
      transplantation with a variety of so-called reduced-intensity settings, has
      indeed raised the hope that we are entering a new era of MDS treatment.

PMID- 18055335
TI  - Immunomodulatory therapy for myelodysplastic syndromes.
AB  - Thalidomide and lenalidomide belong to the proprietary group of immunomodulatory
      drugs (IMiDs) that display broad biologic and pharmacologic properties.
      Encouraging results of clinical studies that evaluated the efficacy of
      thalidomide in patients with myelodysplastic syndromes (MDSs) led to the
      investigation of its structural analogue, lenalidomide, in patients with lower
      risk MDS. The cumulative results of studies that tested lenalidomide in patients
      with interstitial deletion of chromosome 5q, ie, del(5q), showed a high frequency
      of both erythroid and cytogenetic responses (approximately 75% of patients),
      which led to US Food and Drug Administration approval of this agent for this
      cytogenetically defined MDS subset. A multicenter phase III study (MDS-002) that
      investigated the frequency of transfusion response in lower-risk non-del(5q) MDS
      patients showed that lenalidomide had significant erythropoietic activity, albeit
      less robust in lower-risk MDS without del(5q). These studies established
      lenalidomide as an active erythropoietic-remitting agent with novel cytogenetic
      remitting activity in lower-risk MDS patients who would not otherwise benefit
      from therapy with erythropoietic growth factors. The National Comprehensive
      Cancer Network Clinical Practice Guidelines recently added lenalidomide to the
      therapeutic algorithm for MDS as front-line therapy for lower-risk MDS patients
      with del(5q) and transfusion-dependent anemia.

PMID- 18055336
TI  - Treatment options in advanced myelodysplastic syndrome, with emphasis on
      epigenetic therapy.
AB  - Medical management of myelodysplastic syndrome (MDS) remains challenging,
      particularly in advanced stages where the risk of developing acute leukemia is
      very high and the prospect of survival is generally poor. Over the past decade,
      epigenetic changes such as alterations in DNA methylation and histone
      modifications have been well described in MDS and are now recognized as targets
      of therapy (epigenetic therapy). The aim of epigenetic therapy is to reverse
      epigenetic changes and reactivate important genes, thereby modifying the
      malignant phenotype and inducing the clearance of the malignant clone via various
      mechanisms. Epigenetic-modifying agents may also have mechanisms of anticancer
      action unrelated to gene reactivation. The hypomethylating agents azacitidine and
      decitabine induce clinically meaningful remissions or improvements in 30% to 60%
      of patients with this disease, and both agents have been approved in the United
      States for the treatment of advanced and/or symptomatic MDS. Histone deacetylase
      inhibitors belong to another class of epigenetic-modifying agents that also have
      clinical activity in MDS. They are currently being combined with hypomethylating
      agents. Among other available therapeutic options, allogeneic stem cell
      transplantation is the only curative approach for MDS but is also characterized
      by significant morbidities and mortality. We review epigenetic therapy and other
      therapeutic approaches for patients with advanced MDS.

PMID- 18055337
TI  - Activation of FKHRL1 plays an important role in protecting erythroid cells from
      erythropoietin deprivation-induced apoptosis in a human erythropoietin-dependent
      leukemia cell line, UT-7/EPO.
AB  - FKHRL1 is one of the human homologues of DAF-16, which is concerned with
      longevity in Caenorhabditis elegans. Previously, we demonstrated that FKHRL1
      functions downstream of Akt in erythropoietin (EPO) signaling and that it is
      directly phosphorylated by activated Akt. Because phosphorylated FKHRL1 loses its
      transcriptional activity and translocates into the cytoplasm, FKHRL1 appears to
      be nonfunctional in the presence of EPO. Conversely, EPO deprivation leads to
      FKHRL1 dephosphorylation and its translocation into the nucleus, suggesting that
      FKHRL1 becomes active as a transcription factor in the absence of EPO. On the
      basis of these findings, we hypothesized, by analogy with C elegans, that
      erythroid cells possess self-defense machinery against life-threatening
      surroundings. We prepared a dominant-negative mutant of FKHRL1 (FKHRL1-DN)
      lacking the transactivation domain and prepared FKHRL1 small interfering RNA
      (siRNA), and we used constructs to transfect a human EPO-dependent cell line, UT
      7/EPO. In the parental cells, 24-hour EPO deprivation induced transient cell
      cycle arrest without apoptosis. On the other hand, stable transfectants
      expressing FKHRL1-DN or FKHRL1 siRNA underwent rapid apoptosis after EPO
      deprivation in the UT-7/EPO cells. In conclusion, FKHRL1 activation plays an
      important role in the extension of survival of erythroid cells after EPO
      deprivation. This phenomenon appears to correspond to dauer formation in C
      elegans. Thus, the mechanism of lifespan extension may be broadly conserved from
      C elegans to humans.

PMID- 18055338
TI  - Carbamazepine-induced hemolytic and aplastic crises associated with reduced
      glutathione peroxidase activity of erythrocytes.
AB  - Although pure red cell aplasia is a well-known side effect of carbamazepine
      treatment, intravascular hemolytic anemia is rare. We describe a 5-year-old boy
      who developed concurrent intravascular hemolytic anemia and erythroblastopenia,
      probably due to carbamazepine. Carbamazepine treatment was subsequently
      discontinued, and the patient was treated with red blood cell transfusions,
      haptoglobin, and methylprednisolone. His hematologic abnormalities were almost
      fully recovered within 2 weeks. Examination of the patient's and mother's
      erythrocyte enzyme activities revealed mildly decreased erythrocyte glutathione
      peroxidase (GSH-Px) activity. We speculate that patients with reduced GSH-Px
      activity are at a high risk of developing carbamazepine-induced hemolytic crisis
      and/or aplastic crisis.

PMID- 18055339
TI  - Splenic peliosis in a patient with aplastic anemia during danazol therapy.
AB  - We experienced a case of danazol-induced splenic peliosis. A 42-year-old woman
      had taken danazol for refractory aplastic anemia for 2 years. Her anemia
      gradually became aggravated, and the patient complained of intermittent left
      upper-abdominal pain. Because computed tomography scanning showed multiple blood
      filled cavities in the enlarged spleen without intraperitoneal hemorrhage, a
      splenectomy was emergently performed. This report is the first of a case of
      splenic peliosis developing during danazol therapy for aplastic anemia. The
      possible association between the administration of anabolic steroids or danazol
      and the development of peliosis is discussed.

PMID- 18055340
TI  - Dilated cardiomyopathy during the course of hemolytic uremic syndrome.
AB  - A 47-year-old woman presented with severe hemolytic uremic syndrome (HUS)
      followed by heart failure. An echocardiogram showed an ejection fraction of 20%,
      and a cardiac catheterization followed by a myocardial histologic evaluation
      demonstrated dilated cardiomyopathy. Plasma exchange and hemodialysis were
      performed regularly. The later outcomes of renal function and cardiomyopathy were
      favorable. A review of the literature confirmed the rare and severe nature of
      cardiac lesions occurring in the course of HUS. This case indicates the
      importance of cardiac monitoring in HUS and the need for prolonged support.

PMID- 18055341
TI  - Advanced stage is the most important prognostic factor for survival in patients
      with systemic acquired immunodeficiency syndrome-related non-Hodgkin's Lymphoma
      treated with CHOP and highly active antiretroviral therapy.
AB  - In the era of highly active antiretroviral therapy (HAART), the prognosis for
      acquired immunodeficiency syndrome-related lymphomas (ARL) seems to be similar to
      that for aggressive B-cell lymphomas in human immunodeficiency virus (HIV)
      negative patients. This improvement in prognosis might lead to a modification of
      the classic prognostic factors for ARL. We evaluated the prognostic factors for
      response and survival in a series of HIV-infected patients with systemic non
      Hodgkin's lymphoma (NHL) in the HAART era. Forty patients with systemic NHL
      treated with a CHOP-based chemotherapy (cyclophosphamide, doxorubicin,
      vincristine, and prednisone) and HAART were studied. The main clinicopathologic
      and laboratory parameters were recorded in each case. Patients were scheduled to
      receive cycles of CHOP therapy, and all received granulocyte colony-stimulating
      factor. In addition, 9 patients received rituximab (375 mg/m2). The complete
      remission (CR) rate was 62.5% (n = 25). No prognostic factors influencing CR
      attainment were found. The 5-year disease-free survival (DFS) probability (95%
      confidence interval [CI]) was 73% (54%-92%). The median overall survival (OS)
      time was 69.17 months, and the 5-year OS rate (95% CI) was 51% (35%-67%). A
      disease stage of III to IV was the only parameter with prognostic influence on
      DFS. The factors influencing OS were an International Prognostic Index >2, an
      Eastern Cooperative Ecology Group (ECOG) score >2, and a disease stage of III to
      IV. Patients with an advanced stage had a lower OS probability in a multivariate
      analysis (odds ratio, 4.24; 95% CI, 1.24- 14.57). Advanced stage was the main
      prognostic factor predicting survival in ARL treated with CHOP and HAART.

PMID- 18055342
TI  - Phase I trial of FLAGM with high doses of cytosine arabinoside for relapsed,
      refractory acute myeloid leukemia: study of the Japan Adult Leukemia Study Group
      (JALSG).
AB  - This study was designed to determine the optimal high dose for cytosine
      arabinoside (ara-C) in combination with fludarabine, granulocyte colony
      stimulating factor, and mitoxantrone (FLAGM) in adult patients with relapsed or
      refractory acute myeloid leukemia. Nine patients were enrolled at increasing
      dosage levels of ara-C (8, 12, and 16 g/m2 per dose level). Ara-C and fludarabine
      were administered once a day at level 1, once or twice a day at level 2, and
      twice a day at level 3. All patients had grade 4 hematologic toxicity. The most
      common adverse events were of grade 2 or less, with nausea and vomiting being the
      most common (6 events), followed by diarrhea (5 events), and rash (5 events). Of
      the 13 grade 3 nonhematologic toxicities reported, the 2 most common were febrile
      neutropenia (6 events) and disseminated intravascular coagulation (3 events). No
      early deaths were observed. FLAGM with high-dose ara-C was considered safe for
      patients, and the recommended dosage of ara-C in this study was 2 g/m2 every 12
      hours for a total dose of 16 g/m2.

PMID- 18055343
TI  - CD20- and CD56-positive T-cell large granular lymphocyte leukemia in a human T
      cell leukemia virus type 1 carrier.
AB  - A 60-year-old man was diagnosed with asymptomatic T-cell granular lymphocyte (T
      LGL) leukemia in September 2006. He was serologically positive for human T-cell
      leukemia virus type 1 (HTLV-1). However, monoclonal integration of the HTLV-1
      genome was not detected in the peripheral blood, suggesting that HTLV-1 did not
      contribute to the pathogenesis of T-LGL leukemia in the present case.
      Phenotypically, neoplastic cells of our case were CD3+, CD4*, CD8+, CD16-, CD56+,
      CD57*, and T-cell receptor (TCR) alphabeta+. They also coexpressed CD20 antigen
      with weak intensity. This represented a unique case of T-LGL leukemia showing a
      typical clinical and phenotypic features.

PMID- 18055344
TI  - High frequency of BCL2 translocation in Thai patients with follicular lymphomas.
AB  - Follicular lymphoma is characterized by chromosomal translocation involving BCL2
      and immunoglobulin heavy chain genes (IgH). That the incidence of follicular
      lymphoma and the previously reported frequency of BCL2 translocation are lower in
      Asians than in Caucasians implies a different molecular pathology. The study of
      BCL2 rearrangement will yield deeper insights into the pathogenesis of follicular
      lymphomas and into clinical applications of molecular diagnosis for Asian
      follicular lymphoma patients. BCL2 /IgH translocation was analyzed in paraffin
      embedded tissues from follicular lymphoma patients by using polymerase chain
      reaction (PCR) analysis of the major breakpoint region (MBR), the intermediate
      cluster region (ICR), and the minor cluster region. In addition, fluorescence in
      situ hybridization (FISH) analysis with split-signal BCL2 probes was performed.
      PCR analysis revealed BCL2 rearrangement in 12 (23.5%) of 51 cases (10 MBR and 2
      ICR breakpoints). This frequency is lower than the frequencies reported from
      Western countries (40%-60%). DNA sequencing of the breakpoints revealed
      nucleotide insertions suggesting V(D)J recombination-mediated mechanisms. On the
      other hand, FISH analysis revealed 11 (84.6%) of 13 cases with positive signals
      for BCL2 translocation. Our results suggest that BCL2 translocation is essential
      for the pathogenesis of follicular lymphoma in Thai patients. In addition, the
      data demonstrate the low sensitivity of the PCR for diagnostic testing and
      suggest that split-signal FISH is the method of choice.

PMID- 18055345
TI  - Acute myeloid leukemia with multilineage dysplasia in children.
AB  - We retrospectively surveyed pediatric acute myeloid leukemia (AML) patients with
      multilineage dysplasia treated with the AML 99 and the Children's Cancer and
      Leukemia Study Group (CCLSG) AML 9805 protocols. We found only 9 AML patients
      (2.6%) with multilineage dysplasia among the 341 patients with newly diagnosed de
      novo AML. Eight of the 9 patients obtained complete remission (CR) following the
      intensive AML-oriented treatments. Three of 7 patients who underwent stem cell
      transplantation were alive in CR for more than 4 years, and the 2 patients
      treated only with chemotherapy were alive in CR for more than 30 months. We did
      not identify any particular chromosomal abnormalities or differentiation
      according to the French-American-British classification in these 9 patients. No
      reports have described AML with multilineage dysplasia in children, and the
      incidence of the disease is expected to be very low. We plan to conduct a
      prospective pathologic review to select cases with this disease entity in the
      next Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol.

PMID- 18055346
TI  - Neutropenic enterocolitis in children with acute leukemia or aplastic anemia.
AB  - Neutropenic enterocolitis (NE) and acute appendicitis are life-threatening
      conditions that develop in children with severe or prolonged neutropenia
      secondary to acute leukemia and lymphoma. The medical records of 118 patients who
      were treated for acute lymphoblastic leukemia (69 patients), acute myelogenous
      leukemia (22 patients), or aplastic anemia (27 patients) between 1997 and 2006 in
      our hospital pediatric hematology department were examined retrospectively. NE
      was diagnosed in 11 patients (age range, 2.5-16 years) on the basis of clinical
      and laboratory features. Two of these 11 patients had appendicitis in addition to
      NE. Conservative treatment was favored for all patients, but 1 patient with acute
      appendicitis underwent surgery. Neutropenic patients with a hematologic
      malignancy and abdominal pain should receive their diagnoses immediately and
      undergo treatment. NE and acute appendicitis should always be considered in the
      differential diagnosis of abdominal pain. Conservative treatment must be chosen
      initially for patients with NE, and these patients should be evaluated carefully
      for surgery. The criteria for the surgical process are the same as those for
      immunocompetent children. In addition, the close monitoring of hematologic
      factors is necessary.

PMID- 18055347
TI  - Living-donor lobar lung transplantation for broncho-bronchiolitis obliterans
      after allogeneic hematopoietic stem cell transplantation: does bronchiolitis
      obliterans recur in transplanted lungs?
AB  - We report a successful case of living-donor lobar lung transplantation (LDLLT)
      for therapy-resistant broncho-bronchiolitis obliterans (BBO) after allogeneic
      hematopoietic stem cell transplantation (HSCT). Bronchiolitis obliterans (BO) is
      one of the late-onset noninfectious pulmonary complications that occur after
      allogeneic HSCT and is usually resistant to immunosuppressive therapy. A 17-year
      old girl with acute lymphoblastic leukemia (ALL) had undergone allogeneic bone
      marrow transplantation (BMT) from an HLA-matched sibling in 1997. Five years
      later, she relapsed with ALL and was treated with chemotherapy following stem
      cell rescue and donor lymphocyte infusion from the original BMT donor. Eight
      months later, BBO resistant to immunosuppressive therapies, including rituximab,
      developed in combination with chronic graft-versus-host disease (GVHD). In
      February 2004, the patient underwent LDLLT from 2 other family members who were
      mismatched at 3 HLA loci. The patient has been in good health for more than 30
      months following LDLLT and shows no sign of BBO in the transplanted lungs, just
      as with other patients who have undergone lung transplantation for BO associated
      with chronic GVHD. LDLLT may therefore be considered a viable therapeutic option
      for the treatment of BO after allogeneic HSCT.

PMID- 18055348
TI  - Acute-onset pancytopenia in a postpartum lactating woman.

PMID- 18055349
TI  - Bone marrow necrosis as a terminal complication of a very long-lasting
      polycythemia vera.

PMID- 18055350
TI  - New HJV mutation in a patient with hyperferritinemia and H63D homozygosity for
      the HFE gene.

PMID- 18055351
TI  - Right-handers' reaching in contralateral hemispace: a kinematic observation.
AB  - C. Gabbard and C. Helbig (2004) found, when examining seated participants' limb
      selection for reaching and grasping in hemispace, that right-handers preferred to
      switch to the nondominant left arm for objects located approximately 20 degrees
      horizontally from body midline (90 degrees) in left hemispace. In the present
      study, the authors examined 13 strongly lateralized seated right-handers'
      kinematics of reaching to object positions ranging from body midline to 40
      degrees horizontally in left hemispace. Participants executed faster reaches with
      the left arm than with the right arm to objects placed 20 degrees-40 degrees from
      midline, whereas they did not change the proportion of time they spent
      accelerating the hands when the position of the object changed. A 2nd main
      finding was an increase in the left hand's trajectory curvature as object
      position moved farther from midline, with a corresponding decrease in the
      contribution of upper-arm motion to the reach. Those observations suggest that
      the switch from dominant right-arm reaching to nondominant left-arm reaching in
      left hemispace reported in the aforementioned study may have emerged from a shift
      from a shoulder-driven reach to an elbow-driven action.

PMID- 18055352
TI  - A practice-specificity-based model of arousal for achieving peak performance.
AB  - The authors propose a practice-specificity-based model of arousal for achieving
      peak performance. The study included 37 healthy male physical education students
      whom they randomly assigned to a high-arousal (n = 19) or low-arousal group (n =
      18). To manipulate participants' level of arousal, the authors used motivational
      techniques. They used heart rate and the Sport Competition Anxiety Test (R.
      Martens, 1977) to measure the level of arousal that participants achieved. At the
      determined and given arousal state, the 2 groups performed the task (basketball
      free throws) for 18 sessions. Both groups performed a retention test at the 2
      arousal levels immediately after the last exercise session, in the posttest, and
      after 10 days. Results showed that both groups learned the task similarly and
      achieved their peak performance at their experienced arousal level. When tested
      at an arousal level that differed from the one that they experienced throughout
      practice sessions, participants' performance had deteriorated significantly.
      Performance of the task seemed to have integrated with the arousal level of the
      participants during the task learning. The findings of this study suggest a
      practice-specificity-based explanation for achieving peak performance.

PMID- 18055353
TI  - Variation in coordination of a discrete multiarticular action as a function of
      skill level.
AB  - The authors investigated coordination modes that emerged as a function of the
      interaction between skill level and task constraints in a multiarticular kicking
      action. Five skilled, 5 intermediate, and 5 novice participants attempted to
      satisfy specific height and accuracy constraints in kicking a ball over a
      barrier. Skilled and intermediate groups demonstrated a functional coordination
      mode involving less joint involvement at the proximal joints and greater joint
      involvement at distal joints, mimicking a chip-like action in soccer. Conversely,
      the novice group tended to produce larger ranges of motion throughout the kicking
      limb in a driving-like kicking action. Key differences were also found for task
      outcome scores, joint angle-angle relations, and ball-trajectory plots between
      the skilled and intermediate groups and the novice group. Findings from this
      study demonstrated that joint involvement during this discrete multiarticular
      action is a function of skill level and task constraints rather than a
      consequence of a global freezing-freeing strategy suggested in some previous
      research. The authors also highlight the merit of using a model of the
      acquisition of coordination in examining how coordination modes for
      multiarticular actions differ as a function of skill.

PMID- 18055354
TI  - Examining action effects in the execution of a skilled soccer kick by using
      erroneous feedback.
AB  - The authors examined the role of action effects (i.e., ball trajectory) during
      the performance of a soccer kick. Participants were 20 expert players who kicked
      a ball over a height barrier toward a ground-level target. The authors occluded
      participants' vision of the ball trajectory after foot-to-ball contact.
      Participants in a 1st group received erroneous feedback from a video that showed
      a ball-trajectory apex approximately 75 cm lower than that of their actual kick,
      although the ball's landing position was unaltered. Participants in a 2nd group
      received correct video feedback of both the ball trajectory and the landing
      position. The erroneous-feedback group showed a significant bias toward higher
      ball trajectories than did the correct-feedback group. The authors conclude that
      performers at high levels of skill use the visual consequences of the action to
      plan and execute an action.

PMID- 18055355
TI  - Spatial and temporal adaptations that accompany increasing catching performance
      during learning.
AB  - The authors studied changes in performance and kinematics during the acquisition
      of a 1-handed catch. Participants were 8 women who took an intensive 2-week
      training program during which they evolved from poor catchers to subexpert
      catchers. An increased temporal consistency, shift in spatial location of ball
      hand contact away from the body, and higher peak velocity of the transport of the
      hand toward the ball accompanied their improvement in catching performance.
      Moreover, novice catchers first adjusted spatial characteristics of the catch to
      the task constraints and fine-tuned temporal features only later during learning.
      A principal components analysis on a large set of kinematic variables indicated
      that a successful catch depends on (a) forward displacement of the hand and (b)
      the dynamics of the hand closure, thereby providing a kinematic underpinning for
      the traditional transport-manipulation dissociation in the grasping and catching
      literature.

PMID- 18055356
TI  - Snoddy (1926) revisited: time scales of motor learning.
AB  - The authors investigated the time scales of the learning of a mirror-tracing task
      to reexamine G. S. Snoddy's (1926) original claim and the received theoretical
      view (A. Newell & P. S. Rosenbloom, 1981) that motor learning follows a power
      law. Adult participants (N = 16) learned the tracing task in either a normal or a
      reversed visual-image condition over 5 consecutive days of practice and then
      performed 1 day of practice 1 week later and again 1 month later. The reversed
      image group's performance was poorer than that of the normal-image group
      throughout the practice. An exponential was the best fitting function on
      individual data, but the power-law function was the best fit on the group
      averaged data. The findings provided preliminary evidence that 2 characteristic
      time scales, (a) fast, dominated by warm-up, and (b) slow, dominated by
      persistent change, capture individuals' performance in the learning of the mirror
      tracing task.

PMID- 18055357
TI  - Shoulder joint position sense improves with external load.
AB  - Joint position sense (JPS) is important in the maintenance of optimal movement
      coordination of limb segments in functional activities. Researchers have shown
      that the sensitivity of musculotendinous mechanoreceptors increases as muscle
      activation levels increase. In the present study, when 25 participants tried to
      replicate the same presented position, both vector and elevation angle
      repositioning errors decreased linearly as the external load increased up to 40%
      above unloaded shoulder torque. However, external load had no effect on plane
      repositioning error. The results indicated that JPS increased under conditions of
      increasing external load but only in the direction of the applied load. That
      finding indicates that JPS acuity improves as muscle activation levels increase.

PMID- 18055359
TI  - [Quantity and quality of obstetrical care in Baross Street Department of
      Obstetrics and Gynecology between 1990 and 2006].
AB  - AIM AND METHODS: Authors report data from 48,794 deliveries in Semmelweis
      University, I. Department of Obstetrics and Gynecology, from January 1, 1990 to
      December 31, 2006. Data were analyzed based on their computer database, showing
      complexity of obstetrics, genetic counseling and neonatology. RESULTS: In the
      last 17 years the delivery number is increasing, from 2,299 in 1990 to 3,861 in
      2006. Early neonatal mortality rate is decreasing (22 infant deaths per 1,000
      live births in 1990 compared with 6 in 2006). If we do not take those < or =1,000
      grams, intrauterine death outside the institute, and induction of labour because
      of malformation, perinatal mortality is very low, below 6/1,000 deliveries in the
      last 7 years, 2.8 in 2004, 1.8-1.9 in 2005 and 2006. Neonatal and infant
      mortality is also decreasing. There is an increase in the frequency of cesarean
      sections, 15-20% in 1990-1991, and approximately 35% in the last years. Main
      indications are previous cesarean section, threatened fetal hypoxia, dystocia,
      cephalopelvic disproportion, twin pregnancy, hypertension/preeclampsia/HELLP
      syndrome, breech presentation. CONCLUSIONS: Because of the progressive system in
      obstetrics care in Hungary, in this leading institute approximately one fifth of
      the deliveries are preterm, furthermore they also have numerous severe
      pathological cases, though there are favorable changes in perinatal statistics in
      the last 17 years, showing the continuous improvement in obstetrical and
      neonatological care.

PMID- 18055360
TI  - [The effect of carotid stenting on rheological parameters, free radical
      production and platelet aggregation].
AB  - INTRODUCTION: Carotid artery stenting has become a possible treatment of
      significant carotid stenosis. The risk of stent occlusion and restenosis might be
      increased by abnormal rheological conditions amplified platelet aggregation and
      free radical production during the operation. AIMS: The aim of this study was to
      assess the changes of the rheologic parameters, platelet aggregation, and
      oxidative stress after endovascular treatment of carotid stenosis. METHODS: 18
      patients (11 men, ages 68 +/- 9 years and 7 women, ages 62 +/- 8 years) suffering
      from significant carotid stenosis and treated with carotid endovascular
      intervention were examined. Alteration in hemorrheological parameters as well as
      epinephrine-, ADP-, and collagen-induced platelet aggregation were evaluated.
      Oxidative stress was characterized by the determination of catalase activity. The
      measurements were carried out directly before and after the procedure and 1, 2, 5
      days and 1 month following the intervention. Preceding the operation the patients
      were administered a maximum dose (300 mg) of clopidogrel. RESULTS: The
      hematocrit, the plasma fibrinogen concentration (Pfc) and whole blood-, and
      plasma viscosity (Wbv and Pv) decreased significantly immediately after stenting
      ( p < 0.001). By the fifth day following the intervention the Pfc, Wdv, Pv, red
      blood cell (Rbc) aggregation and ADP-induced platelet aggregation increased
      significantly ( p < 0.0001) compared to values measured after the procedure. At 1
      month follow-up these parameters, excepting Wbv, decreased significantly compared
      to measurements made on the 5th day. On the other hand, catalase activity showed
      significant elevation by the end of the first month. CONCLUSION: Hemorrheological
      parameters and platelet aggregation showed specific changes following carotid
      stenting. Abnormal changes of the rheological conditions and increasing platelet
      activation are the most pronounced in the first week following stenting, which
      may lead to the stent's early occlusion. Oxidative stress production returned to
      baseline levels only by the end of the first month.

PMID- 18055361
TI  - [Cerebral complications of diabetes mellitus].
AB  - According to WHO data more than 180 million people suffer from diabetes mellitus
      worldwide and this number could double within 15 years. Normal function of the
      brain is dependent on continuous supply of glucose. In hypoglycemia, production
      of counterregulatory hormones (glucagon, epinephrine, growth hormone, and
      cortisol) increases, the sympathetic system becomes stimulated, and features of
      neuroglycopenia appear in order to save the homeostasis. Hypoglycemia is an
      alarming, actually life threatening condition, but the exposure to chronic
      hyperglycemia has a more detrimental effect on the brain than recurrent exposure
      to severe hypoglycemia. The active neural response to hyperglycemia induces
      changes in gene expression and function. The first steps against hyperosmolality
      are initially adaptive, but later hyperactivation of the hypothalamic
      magnocellular neurosecretory cells leads to their structural damage. Changes in
      hippocampal gene transcription are partially implicated in the deterioration of
      declarative memory. Neurologically passive shunting of excess glucose through
      alternative cellular metabolic pathways induces atherogenic, vascular lesions,
      free radicals, leukoencephalopathy and atrophy of the brain and thus leading to
      cognitive deficits. In physiological conditions insulin has neuroprotective
      effect. However, insulin resistance in the central nervous system correlates with
      insulin resistance in the periphery. Loss of responsiveness to insulin could
      render neurons more susceptible to neurotoxic insults, the protective effect of
      insulin diminishes, and apoptosis, neurodegeneration and the resultant cognitive
      decline are all increased in insulin-resistant patients. Some unclear relations
      appear between diabetes mellitus and Alzheimer's disease. Diabetic patients with
      APOE-4 gene have an increased risk for Alzheimer's disease. Prevalence of
      depression is higher in patients with diabetes mellitus and in turn, depression
      is a risk factor for diabetes mellitus. Simultaneous presence of depression and
      diabetes mellitus tends to worsen the course of both.

PMID- 18055362
TI  - [Fetal oncology].
AB  - The author presents a review of benign and malignant tumors that may affect the
      fetus. Virtually all tumors that occur in children and adults may also develop in
      the fetus, and can be found in the neonate. For their early diagnosis
      ultrasonography and magnetic resonance imaging are of critical importance. These
      techniques represent the cutting edge of contemporary diagnostic technology.
      Regretfully, the progress in perinatal diagnostic methodology has not been
      matched, as yet, by comparable therapeutic options. These are still in their
      experimental stages. Only a few centers perform surgical interventions. Options
      vary about the risk-benefit ratios of the respective operative procedures.

PMID- 18055363
TI  - [Ruptured cirrhotic nodulus treated with collagen patch].
AB  - The authors review the case of a fifty-three-year-old cirrhotic patient. He was
      admitted to the emergency unit with symptoms of acute abdomen and haemorrhagic
      shock. Abdominal bleeding of unknown origin was revealed by UH and CT imaging.
      After circulatory resuscitation, urgent abdominal exploration was indicated.
      During operation arterial bleeding of a ruptured cirrhotic nodulus was found.
      Tacho-Comb (a human fibrinogen/thrombin coated collagen patch) was applied onto
      the hepatic wound. Prompt haemostasis was achieved. The patient was discharged
      after an uneventful postoperative period.

PMID- 18055364
TI  - [The psychiatrist Rudolf Fabinyi: the early years of his career].

PMID- 18055370
TI  - Narcissistic mortification of ageing men.
AB  - The development of a male gender identity involves the task of relinquishing the
      identification with the female primary object. If this separation is experienced
      as loss or expulsion, and responded to by the development and libidinous cathexis
      of phallic-narcissistic characteristics, a specifically male narcissistic
      vulnerability emerges, which can, particularly in ageing men, escalate to
      critical proportions. However, phallic-narcissistic crises in the ageing process
      also contain opportunities for development, provided the losses of age can be
      faced with mourning. The author sets out the statements on the subject of old age
      in the myth of Narcissus and makes use of the concepts of developmental
      psychology. He outlines clinical examples illustrating this problem. Finally, he
      brings to mind the narcissistic plight of the aged Oedipus.

PMID- 18055371
TI  - Freud's prehistoric matrix--owing 'nature' a death.
AB  - This paper is informed by contemporary literature in two fields--neonatal
      research, on the one hand, and the burgeoning interdisciplinary interest in Moses
      and monotheism, on the other. The author postulates that a cluster of traumatic
      events during the first two years of Freud's life compelled him to repeat what
      could not be remembered. Embedded in charged implicit schema, these affects
      remained unprocessed in Freud, who alone of all psychoanalysts did not have an
      analysis, manifesting in an uncanny dread/allure of the 'prehistoric' as a dark
      and dangerous era relating to the archaic feminine/maternal matrix and
      fratricidal murderousness. Furthermore, she cites evidence to suggest that for
      Freud this unconsciously excluded subtext of the preoedipal era became associated
      with ancient Egyptian and Minoan-Mycenaean cultures, a passionate fascination
      actualized in his collection of antiquities yet incongruously absent in his
      theoretical work, with three exceptions--Egyptian allusions in Leonardo's
      unconscious attachment to his archaic mother; the 'Minoan-Mycenaean' analogy on
      discovering the pre-oedipal mother shortly after the death of Freud's own mother;
      and Egypt as cradle of humanity in his uncharacteristically rambling, troubled
      text of Moses and monotheism. The author sees Freud's conceptual avoidance yet
      compulsive reworking of the prehistoric matrix as a symptomatic attempt to expose
      early unformulated representations that 'return to exert a powerful effect'.

PMID- 18055372
TI  - Psychoanalytic transformations.
AB  - The author describes how Bion took Freud's conception of dreams as a form of
      thought and used it as the basis of his theory of transformations. Bion developed
      an expanded theory of 'dream thought', understood as a process of selection and
      transformation of sensory and emotional experiences. In this theory, the work of
      analysis is in turn conceived as a process not only of deciphering symbols, of
      revealing already existing unconscious meanings, but also of symbol production-
      of a process for generating thoughts and conferring meaning on experiences that
      have never been conscious and never been repressed because they have never been
      'thought'. Analysis, in its specific operational sense, becomes a system of
      transformation whereby unconscious somatopsychic processes acquire the conditions
      for representability and become capable of translation into thoughts, words and
      interpretations. The rules of transformation applied by the patient in his
      representations and those applied by the analyst in his interpretations have the
      same importance for the analytic process as those described by Freud for the
      process of dreaming. The author discusses the broad categories of transformation
      adduced by Bion (rigid motion, projective, and in hallucinosis) and introduces
      some further distinctions within them.

PMID- 18055373
TI  - Utopic ideas of cure and joint exploration in psychoanalytic supervision.
AB  - The idea of the decisive and complete cure is deeply rooted in our unconscious
      and in the sacral roots of symbolic healing. Double sets of private theories of
      cure can frequently be found among patients in psychoanalysis and their analysts.
      The utopian cure involves a profound transformation of the personality by way of
      deep regression. The idea of an attainable and more limited cure includes new
      ways of managing old problems. The actual ongoing treatment is then seen as the
      'next-best solution'. The utopian fantasy of creating 'the new person' by means
      of 'proper' psychoanalysis or analytic training has far-reaching consequences for
      psychoanalytic education and supervision. Our awareness of the inevitable
      temptation in the 'utopian state of mind' can help us to trace and focus on
      utopic elements in the supervisory process. Exploration of utopic ideas of all
      the three parties involved can itself be a fruitful and stimulating way of
      working in supervision. An important aim of psychoanalytic supervision is to
      promote a distinct state of mind that can counterbalance utopic ideas and
      counteract the phenomenon of a 'false analytic self'.

PMID- 18055374
TI  - A technique for facilitating the creation of mind.
AB  - There are two forces operating in people. One resists pain and violently opposes
      integration. The other force is slowly bringing coherence and integration to what
      is inside. There has been a tendency within psychoanalysis to focus on the
      former. In this paper the author focuses on the latter. The hypothesis here is
      that if the analyst focuses upon the signs of integration that this assists the
      process of growing self-awareness. The negative transference emerges as the
      undeveloped aspects of the psyche are recognized by the patient.

PMID- 18055375
TI  - Forgiveness, acceptance and the matter of expectation.
AB  - In this paper, the author argues for a dynamic conceptualization of forgiveness
      during psychoanalysis. The trauma of failed expectations in intimate
      relationships is narcissistically dislodging. When legitimate expectations in
      relationships are not met, forgiveness becomes a challenge for ego to restore the
      lost narcissistic balance through the resumption of a significant internal bond.
      The author argues that the ending of any successful analysis is marked by three
      possibilities regarding the patient's relationship to significant others and his
      traumas: in cases where the relationship was marked by minimal expectations, one
      simply learns to accept the wrongdoer without ever feeling the need for
      forgiveness; in cases where a relationship was marked by high expectations, the
      patient can learn to accept the trauma without the will or need to forgive its
      perpetrator. However, even with the painful frustration of high expectations in
      an intimate relationship, the patient can come to forgive his wrongdoer if there
      remains enough of a positive internal bond to be salvaged. The developmental
      roots of such forgiveness, as well as the addictive characteristics of 'nursing a
      grudge' and the conversion of the qualitative mode of seeking fulfillment into a
      quantitative one, are further investigated.

PMID- 18055376
TI  - Raiding the inarticulate: the internal analytic setting and listening beyond
      countertransference.
AB  - The analytic setting exists not only externally but also internally as a
      structure in the mind of the analyst. The internal analytic setting constitutes
      an area of the analyst's mind where reality is defined by unconscious symbolic
      meaning. Clinical examples illustrate how a secure internal setting allows
      flexibility in the external setting without sacrifice of its analytic quality.
      The internal setting can help analysts listen inwardly to themselves in a way
      that is free-floating with regard to their internal processes. This points beyond
      usual ideas of countertransference. An analytic encounter may stir up elements
      that belong to the analyst's psyche which, rather than impeding the analysis, can
      actively enrich it. Seamus Heaney's writings evoke comparisons between listening
      to poems and listening to patients, and a week in a patient's analysis is
      described in relation to these themes.

PMID- 18055377
TI  - Thinking extreme social violence: the model of the literary plague.
AB  - The author uses literary plagues as a model for thinking psychoanalytically about
      the basic anxieties activated among perpetrators of sanctioned massacres. The
      model of the plague allows abstracting an underlying primitive psychological
      organization characterized by syncretism and a powerful anxiety of de
      differentiation and confusion, leading characteristically to imitative behavior
      within the in-group as well as to the disavowal of the out-group members
      similarities to oneself, i.e. the disavowal of the other's humanity. Recognizing
      the historical and social foundations of discrimination and genocide, the author
      analyzes the interaction between group and individual processes that allow
      ordinary people to join daily acts of immoral violence. She dramatizes the model
      of the plague through a psychoanalytic reading of three literary plagues: Thebes'
      plague according to Sophocles, Camus's chronicle of the plague in Oran, and
      Saramago's meditation on the plague of white blindness.

PMID- 18055378
TI  - Space and time in psychoanalytic listening.
AB  - The analytic situation is by definition traumatic because it evokes
      hilflosigkeit, the state of helplessness of the newborn infant, which is the
      prototype of the traumatic situation, and at the origin of the experience of
      anxiety. The author addresses the chain of associations between the state of
      helplessness, repetition compulsion, trauma, infantile sexuality, pleasure and
      displeasure, which lie at the core of the transference experience, and which find
      their ultimate expression in the analyst's listening. The discovery of the
      compulsion to repeat instituted a paradigmatic shift in Freud's formulations,
      emphasizing the process of repetition of trauma, and instituting a link between
      the network of concepts indicated above. In the clinical example discussed, the
      author defines the psychoanalytic process by the primacy of sexuality, the erotic
      passivation in the transference that evokes the traumatic childhood sexual scene.
      Sexuality and sexual phantasies are at the centre of the elaboration of meaning.
      Furthermore, the author distinguishes between two types of interpretations,
      namely 'open' and 'closed'.

PMID- 18055379
TI  - 'Are you a woman--or a flower?' The capacity to experience beauty.
AB  - Being surprised by beauty, being drawn to and moved by it and surrendering to its
      sensory nature are all part of beauty's emotionally transformative power. And
      yet, psychoanalysis has had little to say about such an enriching dimension of
      psychological life. The author highlights how experiencing beauty is a capacity
      that is not isolated but is part of the lifelong experience of being changed by
      and changing the experience of the world we live in. She suggests that the
      capacity to experience beauty takes different forms at distinct points in
      development and in psychoanalytic treatments. The author describes two clinical
      occasions from a case where an analytic pair struggled to develop a greater
      capacity to experience beauty over time. She discusses how a theory of the
      aesthetic conflict was useful in helping to understand her patient's inner object
      world but was not sufficient when it came to understanding the experience of
      beauty. She shows how for both patient and analyst, experiencing beauty's full
      effect required responding to the call toward emotional life, surrendering to the
      surprise and the unknown, and letting go of the mind's struggle to find meaning
      and opening up to transforming and being transformed through sensory experience.

PMID- 18055380
TI  - Learning from experience: Bion's concept of reverie and Buddhist meditation. A
      comparative study.
AB  - The author argues for a common denominator between Bion's view and the Buddhist
      view of mental development. In both thought systems, mental growth is synonymous
      to learning from experience. The author closely examines Bion's concept of
      attention and compares it to mindfulness, a major factor in Buddhist meditation.
      In both doctrines, attention must be isolated from other mental processes in
      order to attain learning from experience. The author compares reverie to the
      state of mind of equanimity. She argues that enhancement of the ability of
      reverie, or improving the inner container such that it can hold any content while
      unmoved by desire, is the purpose of Buddhist practice. Both view the mind as
      capable of transcending its own restrictions and 'the capacity to know anything'
      as attainable through disciplined practice.

PMID- 18055381
TI  - The influence of extreme traumatization on body, mind and social relations.
AB  - Extreme traumatization affects the individual's relation to others in several
      social and psychological ways. The post-traumatic experiences are characterized
      by helplessness, insecurity, anxiety, loss of basic trust, and fragmentation of
      perspectives on one's own life. Special considerations should be given to the
      destruction of the ability to regulate negative emotions (extreme fear, distress,
      anguish, anger, rage, shame) in relation to others and activate internal good and
      empathic object relations. Destruction of the capacity for symbolization of
      traumatic experience may threaten the mind with chaotic states against which the
      'I' tries to defend itself and find a balanced psychic mise-en-scene. The authors
      emphasize three dimensions that the analyst should observe in his understanding
      of the traumatized mind and its conflicts. The proposed dimensions are called the
      body-other dimension, the subject-group dimension, and the subject-discourse
      dimension. All three dimensions have specific structural characteristics that are
      expressed in the analytic relation. Extreme trauma causes disturbances in each of
      these dimensions. The authors present clinical material from a traumatized
      refugee to illustrate the analytic work.

PMID- 18055382
TI  - Psychoanalytic reflections on the body in racism, homophobia and misogyny.

PMID- 18055383
TI  - Further thoughts on: Julie's museum: the evolution of thinking, dreaming and
      historicization in the treatment of traumatized patients.

PMID- 18055385
TI  - Population synchrony in small-world networks.
AB  - Network topography ranges from regular graphs (linkage between nearest neighbours
      only) via small-world graphs (some random connections between nodes) to
      completely random graphs. Small-world linkage is seen as a revolutionary
      architecture for a wide range of social, physical and biological networks, and
      has been shown to increase synchrony between oscillating subunits. We study small
      world topographies in a novel context: dispersal linkage between spatially
      structured populations across a range of population models. Regular dispersal
      between population patches interacting with density-dependent renewal provides
      one ecological explanation for the large-scale synchrony seen in the temporal
      fluctuations of many species, for example, lynx populations in North America,
      voles in Fennoscandia and grouse in the UK. Introducing a small-world dispersal
      kernel leads to a clear reduction in synchrony with both increasing dispersal
      rate and small-world dispersal probability across a variety of biological
      scenarios. Synchrony is also reduced when populations are affected by globally
      correlated noise. We discuss ecological implications of small-world dispersal in
      the frame of spatial synchrony in population fluctuations.

PMID- 18055386
TI  - Agonistic signals received by an arthropod filiform hair allude to the prevalence
      of near-field sound communication.
AB  - Arthropod filiform hairs respond to air particle movements and are among the most
      sensitive animal sensory organs. In many species, they are tuned to detect
      predators or prey and trigger escape or prey capture behaviours. Here we show for
      the first time that these hairs also receive intraspecific near-field sound
      signals in an arachnid. During agonistic encounters, whip spiders (Arachnida,
      Amblypygi) perform antenniform leg vibration (ALV) displays that have
      significantly longer duration in contest winners than losers. During an ALV
      display: (i) the vibrating antenniform leg of the displaying whip spider is
      positioned close to the trichobothria (filiform hairs) on its opponent's walking
      legs, (ii) the vibrating antenniform leg can excite these trichobothria via air
      movements and without direct contact, (iii) the antenniform leg of the displaying
      whip spider vibrates at a frequency that causes particularly strong, sustained
      excitation and little adaptation in the trichobothria, and (iv) the duration of
      an ALV display can be extracted from the response of a trichobothrium. Since
      filiform hairs are widespread among arthropods, communication via such hairs
      could be extremely prevalent.

PMID- 18055388
TI  - Carotenoid trade-off between parasitic resistance and sexual display: an
      experimental study in the blackbird (Turdus merula).
AB  - Many parasites depress the expression of the carotenoid-based colour displays of
      their hosts, and it has been hypothesized that animals face a trade-off in
      carotenoid allocation between immune functions and 'degree of ornamentation'.
      While numerous correlative studies suggest that parasite infection decreases the
      intensity of carotenoid-based colour displays, the existence of this trade-off
      has never been demonstrated experimentally in a host-parasite model. In this
      study, we used the blackbird (Turdus merula) and Isospora (an intestinal
      parasite) to assess whether this trade-off does indeed exist. Blackbirds were
      supplemented with carotenoids while simultaneously being exposed to parasites.
      Supplemented males circulated more carotenoids in the blood and developed more
      brightly coloured bills than unsupplemented males. In addition, supplementation
      slowed down the replication rate of parasites. Supplementation with carotenoids
      enabled infected birds to maintain their bill coloration, whereas birds that were
      infected but not supplemented showed reduced bill coloration. At the same time,
      infection slowed carotenoid assimilation in the blood. Overall, we demonstrated
      that bill colour reflects a bird's health, and that only males with a carotenoid
      rich diet are capable of coping with costs associated with parasitic infection.
      Carotenoids are thus traded off between host physiological response to parasites
      and secondary sexual traits. Further investigations are required to determine the
      physiological mechanisms that govern this trade-off.

PMID- 18055389
TI  - The effect of stimuli that isolate S-cones on early saccades and the gap effect.
AB  - Disappearance of the fixation spot before the appearance of a peripheral target
      typically reduces average saccadic reaction times (the gap effect) and may also
      produce a separate population of early or express saccades. The superior
      colliculus (SC) is generally believed to be critically involved in generating
      both effects. As the direct sensory input to the SC does not encode colour
      information, to determine whether this input was critical in generating the gap
      effect or express saccades we used coloured targets which this pathway cannot
      distinguish. Our observers still made early saccades to colour-defined targets,
      but these were anticipations in response to the offset of the non-coloured
      fixation target. We also show that a gap effect still occurs when either the
      fixation target or the peripheral target is colour defined, suggesting that
      direct sensory input to the SC is not required and that information about the
      location of colour-defined targets is abstracted prior to processing within the
      SC.

PMID- 18055390
TI  - Intraspecific variation in a generalist herbivore accounts for differential
      induction and impact of host plant defences.
AB  - Plants and herbivores are thought to be engaged in a coevolutionary arms race:
      rising frequencies of plants with anti-herbivore defences exert pressure on
      herbivores to resist or circumvent these defences and vice versa. Owing to its
      frequency-dependent character, the arms race hypothesis predicts that herbivores
      exhibit genetic variation for traits that determine how they deal with the
      defences of a given host plant phenotype. Here, we show the existence of distinct
      variation within a single herbivore species, the spider mite Tetranychus urticae,
      in traits that lead to resistance or susceptibility to jasmonate (JA)-dependent
      defences of a host plant but also in traits responsible for induction or
      repression of JA defences. We characterized three distinct lines of T. urticae
      that differentially induced JA-related defence genes and metabolites while
      feeding on tomato plants (Solanum lycopersicum). These lines were also
      differently affected by induced JA defences. The first line, which induced JA
      dependent tomato defences, was susceptible to those defences; the second line
      also induced JA defences but was resistant to them; and the third, although
      susceptible to JA defences, repressed induction. We hypothesize that such
      intraspecific variation is common among herbivores living in environments with a
      diversity of plants that impose diverse selection pressure.

PMID- 18055392
TI  - Evolution of aquatic insect behaviours across a gradient of disturbance
      predictability.
AB  - Natural disturbance regimes--cycles of fire, flood, drought or other events-
      range from highly predictable (disturbances occur regularly in time or in concert
      with a proximate cue) to highly unpredictable. While theory predicts how
      populations should evolve under different degrees of disturbance predictability,
      there is little empirical evidence of how this occurs in nature. Here, we
      demonstrate local adaptation in populations of an aquatic insect occupying sites
      along a natural gradient of disturbance predictability, where predictability was
      defined as the ability of a proximate cue (rainfall) to signal a disturbance
      (flash flood). In controlled behavioural experiments, populations from
      predictable environments responded to rainfall events by quickly exiting the
      water and moving sufficiently far from the stream to escape flash floods. By
      contrast, populations from less predictable environments had longer response
      times and lower response rates, reflecting the uncertainty inherent to these
      environments. Analysis with signal detection theory showed that for 13 out of 15
      populations, observed response times were an optimal compromise between the
      competing risks of abandoning versus remaining in the stream, mediated by the
      rainfall-flood correlation of the local environment. Our study provides the first
      demonstration that populations can evolve in response to differences in
      disturbance predictability, and provides evidence that populations can adapt to
      among-stream differences in flow regime.

PMID- 18055393
TI  - [Carrier detection in families affected by Duchenne/Becker muscular dystrophy].
AB  - Duchenne/Becker muscular dystrophy is a severe, recessive, X-linked neuromuscular
      disease with an incidence of 1/3500 (Duchenne type) and 1/30,000 (Becker type) in
      newborn boys. The gene responsible for the Duchenne/Becker muscular dystrophy
      phenotype is located at Xp21 and its 427 kD protein product is called dystrophin.
      Deletions, point mutations and rarely duplications can occur almost anywhere in
      the DMD gene, which makes the molecular diagnosis difficult. Multiple polymerase
      chain reactions detect 95% of deletions in affected males [2, 4], but are not
      suitable for carrier detection in female relatives. Southern-blot analysis with
      six different cDNA probes covers the whole 14 kb dystrophin transcript and allows
      the detection of female carriers by comparing the intensity of the signals
      corresponding to the different exons. This method is time consuming compared to
      the newly introduced multiple ligation-dependent probe amplification method.
      Multiple ligation-dependent probe amplification is a method suitable for relative
      quantification of several DNA sequences in one reaction. The authors report
      results on 93 cases where the carrier status was analysed simultaneously by cDNA
      hybridisation and multiple ligation-dependent probe amplification technique. In
      42 cases the carrier state was confirmed and in this carrier population the
      authors additionally detected two cases with duplication, two cases with one copy
      of the whole dystrophin gene and three manifest carrier females. On the basis of
      these results the MLPA technique, which has been newly introduced in Hungary,
      proved to be a sensitive and quick method for the detection of carrier state in
      the DMD/BMD disease. Moreover, the exact deletion or duplication border can be
      detected and as a result, prediction on the phenotype can be given. This will
      provide the right therapeutic intervention for the affected patients in the
      future.

PMID- 18055391
TI  - Symbiont-mediated protection.
AB  - Despite the fact that all vertically transmitted symbionts sequester resources
      from their hosts and are therefore costly to maintain, there is an extraordinary
      diversity of them in invertebrates. Some spread through host populations by
      providing their hosts with fitness benefits or by manipulating host sex ratio,
      but some do not: their maintenance in host lineages remains an enigma. In this
      review, I explore the evolutionary ecology of vertically transmitted symbionts
      and their impact on host resistance, and provide an overview of the evidence for
      the three-way interactions between these symbionts, natural enemies and
      invertebrate hosts. A number of recent empirical and theoretical studies suggest
      that vertically transmitted symbionts may protect their hosts from pathogens. If
      this 'symbiont-mediated protection' is widespread, it is likely that vertically
      transmitted symbionts contribute significantly to variation in measures of
      invertebrate resistance to natural enemies.

PMID- 18055387
TI  - Sexual and social stimuli elicit rapid and contrasting genomic responses.
AB  - Sensory physiology has been shown to influence female mate choice, yet little is
      known about the mechanisms within the brain that regulate this critical
      behaviour. Here we examine preference behaviour of 58 female swordtails,
      Xiphophorus nigrensis, in four different social environments (attractive and
      unattractive males, females only, non-attractive males only and asocial
      conditions) followed by neural gene expression profiling. We used a brain
      specific cDNA microarray to identify patterns of genomic response and candidate
      genes, followed by quantitative PCR (qPCR) examination of gene expression with
      variation in behaviour. Our microarray results revealed patterns of genomic
      response differing more between classes of social stimuli than between presence
      versus absence of stimuli. We identified suites of genes showing diametrically
      opposed patterns of expression: genes that are turned 'on' while females interact
      with attractive males are turned 'off' when interacting with other females, and
      vice versa. Our qPCR results identified significant predictive relationships
      between five candidate genes and specific mate choice behaviours (preference and
      receptivity) across females exposed to males, with no significant patterns
      identified in female or asocial conditions or with overall locomotor activity.
      The identification of stimulus- and behaviour-specific responses opens an
      exciting window into the molecular pathways associated with social behaviour and
      mechanisms that underlie sexual selection.

PMID- 18055394
TI  - [Role of obesity in colorectal carcinogenesis].
AB  - The obesity is the second most frequent cause of death which can be prevented. It
      elevates the risk of cardiovascular diseases, diabetes mellitus type 2, cancers
      and premature mortality. Overweight and obesity responsible for 14% of cancer
      caused death in males, and 20% in females, respectively. Authors review the
      connection between obesity, metabolic syndrome and related metabolic alterations
      with colorectal cancers. They summarize the role of inflammation,
      hyperinsulinemia, insulin-like growth factor-I and adipokines in the colorectal
      carcinogenesis.

PMID- 18055395
TI  - [Depression, anxiety and quality of life in pediatric asthma].
AB  - AIMS: The study's objective was to examine depression, anxiety and quality of
      life according to age and asthma status in pediatric asthma in a pediatric
      university department. METHODS: 108 patients, age: 11.75 +/- 3.10 (mean +/- SD)
      years (boys 11.6 +/- 2.8 years and girls 12.1 +/- 3.7 years) completed the Child
      Depression Inventory, the State Trait Anxiety Inventory for Children, the
      Pediatric Asthma Quality of Life Questionnaire, and a symptom score. Forced
      expiratory volume in one second was also measured. RESULTS: Mean forced
      expiratory volume in one second percent was 97.4 +/- 12.8. 23 patients (21%) had
      intermittent asthma, 40 patients (37%) had mild persistent, 43 patients (40%) had
      moderate persistent, 2 patients (2%) had severe persistent asthma. Pediatric
      asthma patients scored 9.36 +/- 5.57 points in the depression questionnaire.
      Patients showed as many depressive symptoms as the Hungarian average population,
      pre-adolescent boys with asthma showed even less. Children with asthma scored
      31.16 +/- 4.61 points on the anxiety questionnaire; (boys 30.64 +/- 4.29, girls
      32.67 +/- 5.27). Children with asthma have the same anxiety level as their
      healthy peers. On the quality of life questionnaire asthmatic children reached
      6.18 +/- 1.00 (2.87-7.00); adolescent girls scored the worst (5.62 +/- 1.28).
      Adolescent asthmatic girls have the worst quality of life. Boys reach better
      quality of life scores as they grow older ( p = 0.02). Girls with adolescence
      have a tendency of decreasing quality of life, although the difference is not
      significant. In adolescence, asthmatic girls experience more quality of life
      deprivation than boys ( p = 0.013). Depression score, anxiety, or quality of life
      showed no difference between the intermittent and persistent asthmatic groups.
      Children in the symptomatic subgroup experienced poorer quality of life.
      Depression and anxiety were not affected by current asthma symptoms. There was no
      significant difference in depression, anxiety or quality of life scores according
      to age. CONCLUSION: The psychological status of children with asthma is fairly
      good. One should concentrate more on the quality of life of girls in adolescence.
      The good pediatric care of childhood asthmatics helps to avoid the psychological
      consequences of the disease.

PMID- 18055396
TI  - [Review of the application of synthetic bone grafts. The role of the gypsum in
      bone substitution: molecular biological approach, based on own research results].
AB  - Properties of bone graft can determine the effectiveness, short and long term
      success of bone substitution procedure. In this paper, a brief report about
      advantages and disadvantages of modern bone substitution processes is presented
      and authors have explicated the opportunity of the usage of gypsum as bone graft.
      Recently, calcium sulfate dihydrate has been demonstrated as safe biodegradable
      osteoconductive bone void filler. However, its exact mechanism of action on bone
      cells and the molecular process of bone substitution is yet unknown. Authors have
      investigated the effect of gypsum on bone cells using molecular biology methods.
      Gypsum proved to be an ideal culture surface for proliferation of mice
      preosteoblastic cells, while polymethilmetacrylate bone cement - generally used
      in clinical practice as bone substitution material - inhibited cell growth. Gene
      expression profile of cells has significantly changed on gypsum surface - genes
      involved in new bone formation have expressed with an increased ratio - and an
      increased alkaline phosphatase activity has been measured from these cultures.
      Our results support the use of gypsum as synthetic bone graft and new properties
      of calcium sulfate dihydrate have been demonstrated due to molecular biological
      approach.

PMID- 18055397
TI  - [Multiple angiodysplasias diagnosed by capsule endoscopy].
AB  - Angiodysplasias are the most frequent vascular lesions of the gastrointestinal
      tract and sources of significant mortality from bleeding. Small bowel
      angiodysplasias account for approximately 40% of cases of gastrointestinal
      bleeding with obscure origin and represent the single most common cause for
      hemorrhage in this subset of patients. Their cause is unknown but most are
      probably acquired and the result of a degenerative process associated with aging.
      The difficulty of their diagnosis stems from their multiple appearance and small
      size. Examinations that have been performed so far support that the sensitivity
      of capsule endoscopy (CE) performed during active bleeding was higher than in
      case of previous overt bleeding and occult bleeding. CASE REPORT: A 61-year-old
      female patient, who has received anticoagulant therapy for 13 years, presented
      with recurrent gastrointestinal bleeding of obscure origin underwent wireless
      capsule endoscopy after negative upper endoscopy and colonoscopy. CE showed non
      bleeding typical angiodysplasia in the antrum of the stomach and active bleeding
      in the first third of jejunum without a visible bleeding source. As the next
      diagnostic step we performed selective mesenteric angiography to clarify the
      diagnosis and at the same time we also applied radiological intervention.
      CONCLUSION: Capsule endoscopy changed in practice guidelines for obscure bleeding
      and became the first-line method for evaluation of patient after upper endoscopy
      and colonoscopy have been shown to be negative. If the examination is performed
      early, CE could shorten considerably the time to diagnosis, lead to definitive
      treatment and numerous examinations with low yield could be avoided. The therapy
      of small bowel angiodysplasias is questionable. Radiological intervention poses
      the least load for the patient.

PMID- 18055401
TI  - [Interview with dr. Sandor Gardo].

PMID- 18055406
TI  - Driving a hard bargain: sex ratio and male marriage success in a historical US
      population.
AB  - Evolutionary psychologists have documented a widespread female preference for men
      of high status and resources, and evidence from several populations suggests that
      this preference has real effects on marriage success. Here, we show that in the
      US population of 1910, socioeconomic status (SES) had a positive effect on men's
      chances of marrying. We also test a further prediction from the biological
      markets theory, namely that where the local sex ratio produces an oversupply of
      men, women will be able to drive a harder bargain. As the sex ratio of the states
      increases, the effect of SES on marriage success becomes stronger, indicating
      increased competition between men and an increased ability to choose on the part
      of women.

PMID- 18055407
TI  - African elephants have expectations about the locations of out-of-sight family
      members.
AB  - Monitoring the location of conspecifics may be important to social mammals. Here,
      we use an expectancy-violation paradigm to test the ability of African elephants
      (Loxodonta africana) to keep track of their social companions from olfactory
      cues. We presented elephants with samples of earth mixed with urine from female
      conspecifics that were either kin or unrelated to them, and either unexpected or
      highly predictable at that location. From behavioural measurements of the
      elephants' reactions, we show that African elephants can recognize up to 17
      females and possibly up to 30 family members from cues present in the urine-earth
      mix, and that they keep track of the location of these individuals in relation to
      themselves.

PMID- 18055408
TI  - Marrying women 15 years younger maximized men's evolutionary fitness in
      historical Sami.
AB  - Most men marry younger women. This has been attributed to men selecting young
      women due to their high reproductive value and women preferring older men due to
      their wealth and high social status. Such mate preferences have been suggested to
      be adaptive, but despite a flourishing number of studies on the mate selection
      patterns themselves, little is still known of their actual fitness consequences.
      We examined how the age difference between spouses who married only once affected
      their lifetime reproductive success in historical monogamous Sami populations. We
      found that men maximized their fitness by marrying women approximately 15 years
      younger and vice versa. However, most couples failed to marry optimally. Only 10%
      of marriages fell within the optimal parental age difference, suggesting that
      cultural and ecological constraints for maximizing fitness were considerable.
      Those who succeeded in marrying optimally were the most preferred partners: young
      women and old men. Our findings indicate that, in Sami, parental age difference
      was under natural and sexual selection, as suggested by evolutionary theory.

PMID- 18055409
TI  - Scaling of gas exchange cycle frequency in insects.
AB  - Previously, it has been suggested that insect gas exchange cycle frequency (fC)
      is mass independent, making insects different from most other animals where
      periods typically scale as mass-0.25. However, the claim for insects is based on
      studies of only a few closely related taxa encompassing a relatively small size
      range. Moreover, it is not known whether the type of gas exchange pattern
      (discontinuous versus cyclic) influences the fC-mass scaling relationship. Here,
      we analyse a large database to examine interspecific fC-mass scaling. In
      addition, we investigate the effect of mode of gas exchange on the fC-scaling
      relationship using both conventional and phylogenetically independent approaches.
      Cycle frequency is scaled as mass(-0.280) (when accounting for phylogenetic non
      independence and gas exchange pattern), which did not differ significantly from
      mass(-0.25). The slope of the fC-mass relationship was shallower with a
      significantly lower intercept for the species showing discontinuous gas exchange
      than for those showing the cyclic pattern, probably due to lower metabolic rates
      in the former. Insects therefore appear no different from other animals insofar
      as the scaling of gas exchange fC is concerned, although gas exchange fC may
      scale in distinct ways for different patterns.

PMID- 18055410
TI  - Does parental age difference affect offspring count in humans? Comment on Fieder
      and Huber.

PMID- 18055411
TI  - Symbiont acquisition alters behaviour of stinkbug nymphs.
AB  - In parasitic associations, the evolutionary interest of a symbiont contradicts
      that of a host, which sometimes causes the phenomena so-called 'parasite
      manipulation' wherein symbiont infection alters host behaviour to facilitate its
      vertical/horizontal transmission. In mutualistic associations, meanwhile,
      symbiont-induced alteration of host behaviour that enhances its transmission has
      been little described. Here we report such a case in the stinkbug Megacopta
      punctatissima associated with an obligate gut bacterium. When female stinkbugs
      lay eggs, small particles called 'symbiont capsules' are deposited underside of
      the egg mass. Newborn nymphs immediately acquire the symbiont from the capsule,
      and then aggregate and become quiescent. By manipulating the levels of symbiont
      supply to newborn nymphs experimentally, we demonstrated that (i) experimental
      depletion of the symbiont resulted in the occurrence of wandering nymphs, (ii)
      the less symbiont supply, the more wandering nymphs, and (iii) almost all
      wandering nymphs were either symbiont-free or symbiont-depleted, whereas the
      majority of resting nymphs were infected with sufficient titres of the symbiont.
      These results strongly suggest that the nymphal behaviour is strongly influenced
      by the success/failure of the symbiont acquisition, thereby ensuring transmission
      of the essential symbiont and minimizing the energy and time spent for the
      activity.

PMID- 18055412
TI  - Parental aggression against dependent young results in task partitioning in a
      cooperatively breeding bird.
AB  - In cooperatively breeding species, helpers can alleviate reproductive constraints
      by assuming the role of primary carers to first-born young, liberating breeders
      to invest in subsequent broods. However, evidence on how first-born young are
      transferred to helpers is currently lacking. We propose that breeder-offspring
      aggression might facilitate inter-brood division and test this idea using data
      from a wild population of cooperatively breeding pied babblers (Turdoides
      bicolor). After second-brood young hatch, breeders become increasingly aggressive
      to first-brood fledglings and attack them when they beg for food. After an
      attack, fledglings reduce begging. Helpers are much less aggressive to begging
      fledglings and fledglings subsequently tend to target helpers, rather than
      breeders, when begging for food. In this way, first-born dependent young are
      transferred to helpers, resulting in a partitioning of tasks among breeders and
      helpers. Task partitioning in eusocial insects is thought to be determined by the
      morphological or physiological characteristics of individuals. This complementary
      study suggests that flexible behavioural strategies may also result in
      specialized roles in cooperatively breeding vertebrates.

PMID- 18055413
TI  - Early Palaeozoic dentine and patterned scales in the embryonic catshark tail.
AB  - Regular scale patterning, restricted to the caudalmost tail and organized into
      two opposing rows on each side of the tail, is observed in few chondrichthyans.
      These evenly spaced scales, in dorsal and ventral rows, develop in an iterative
      sequence from the caudal tip, either side of the notochord. They are subsequently
      lost as a scattered pattern of placoid scales develops on the body and fins. An
      identical organized pattern is observed in tail scales of Scyliorhinus canicula
      (catshark), where the expression of sonic hedgehog signal is restricted to the
      epithelium of developing scales and remains localized to the scale pocket.
      Regulation of iterative scale position by sonic hedgehog is deeply conserved in
      vertebrate phylogeny. These scales also reveal an archaic histological structure
      of a dentine type found in the oldest known shark scales from the Ordovician and
      Silurian. This combination of regulated pattern and ancient dentine occurs only
      in the tail, representing the primary scalation. Scattered body scales in
      elasmobranchs such as S. canicula originate secondarily from differently
      regulated development, one with typical orthodentine around a central pulp
      cavity. These observations emphasize the modular nature of chondrichthyan scale
      development and illustrate previously undetected variation as an atavism in
      extant chondrichthyan dentine.

PMID- 18055414
TI  - Placoderm muscles and chordate interrelationships.

PMID- 18055415
TI  - Optimal age difference cannot differ between monogamous males and females: a
      comment on Fieder and Huber.

PMID- 18055416
TI  - Polyphyletic origin of toxic Pitohui birds suggests widespread occurrence of
      toxicity in corvoid birds.
AB  - Pitohui birds from New Guinea have been found to contain a toxin otherwise only
      found in neotropical poison arrow frogs. Pitohuis have been considered to be
      monophyletic and thus toxicity is thought to have evolved once in birds. Here, we
      show that Pitohuis, rather than being a tight-knit group, are polyphyletic and
      represent several lineages among the corvoid families of passerine birds. This
      finding demonstrates that the ability to be toxic is widespread among corvoid
      birds and suggests that additional members of this radiation, comprising more
      than 700 species, could prove to be toxic. It is postulated that toxic birds
      ingest the toxin through their insect diet and excrete it through the uropygial
      gland, from where it is applied to the skin and feathers. Thus, the ability to
      become toxic is most likely an ancestral condition but variation in diet
      determines the extent to which toxicity is expressed among corvoid birds.
      Variability in toxicity levels further suggests that the main function of the
      toxin is that of a deterrent against ectoparasites and bacterial infection rather
      than being a defence against predators as initially proposed.

PMID- 18055417
TI  - The effect of network mixing patterns on epidemic dynamics and the efficacy of
      disease contact tracing.
AB  - In networks, nodes may preferentially contact other nodes with similar
      (assortatively mixed) or dissimilar (disassortatively mixed) numbers of contacts.
      Different patterns of contact support different epidemic dynamics, potentially
      affecting the efficacy of control measures such as contact tracing, which aims to
      identify and isolate nodes with infectious contacts. We used stochastic
      simulations to investigate the effects of mixing patterns on epidemic dynamics
      and contact-tracing efficacy. For uncontrolled epidemics, outbreaks occur at
      lower infection rates for more assortatively mixed networks, with faster initial
      epidemic growth rate and shorter epidemic duration than for disassortatively
      mixed networks. Contact tracing performs better for assortative mixing where
      epidemic size is large and tracing rate low, but it performs better for
      disassortative mixing at higher contact rates. For assortatively mixed networks,
      disease spreads first to highly connected nodes, but this is balanced by contact
      tracing quickly identifying these same nodes. The converse is true for
      disassortative mixing, where both disease and tracing are less likely to target
      highly connected nodes. For small epidemics, contact tracing is more effective on
      disassortative networks due to the greater resilience of assortative networks to
      link removal. Multi-step contact tracing is more effective than single-step
      tracing for assortative mixing, but this effect is smaller for disassortatively
      mixed networks.

PMID- 18055418
TI  - Thyroid cancer in childhood: management strategy, including dosimetry and long
      term results.
AB  - Thyroid cancer, although very rare in childhood, represents the most common
      pediatric endocrine neoplasia. The low incidence and the resulting limited
      availability of prospective, randomized trials lead to a lack of evidence- based
      recommendations for treatment strategies. Total thyroidectomy and
      lymphadenectomy, when indicated, followed by ablative radioiodine treatment, are
      considered the cornerstones of initial patient management which decrease the risk
      of relapse. On the other hand, less aggressive treatment modalities should also
      be aimed at due to the high life expectancy of this special patient group and the
      potential impairment of the quality of life. These considerations have led to
      individualized "tailored" therapeutic approaches based on prior risk
      stratification. This article mainly deals with novel nuclear medicine concepts
      for dosing regimens in radioiodine therapy.

PMID- 18055419
TI  - The role of the Wnt signaling pathway in osteoblast commitment and
      differentiation.
AB  - Wnts are a large family of proteins that participate in an array of cellular
      biological processes such as embryogenesis, organogenesis and tumor formation.
      These proteins bind to membrane receptor complexes comprised of a frizzled (Fz) G
      protein-coupled receptor and other membrane co-receptors forming molecular groups
      that initiate, at least, three different intracellular signaling cascades leading
      to nuclear generation of transcription factors which regulate various cellular
      events. These events result in selective cellular differentiation, reduction or
      inhibition of the apoptotic mechanisms or changes in the biologic behavior of
      various cell lines. During the last decade, canonical Wnt signaling has been
      shown to play a significant role in the control of osteoblastogenesis and bone
      formation. In several clinical cases, mutations have been found in the Wnt
      receptor complexes that are associated with changes in bone mineral density and
      fractures. Loss-of-function mutations in LRP5 receptors cause, osteoporosis
      pseudoglioma syndrome, while gain-of-function mutations in the same group lead to
      high bone mass phenotypes. Furthermore, osteocytes secrete proteins such as
      sclerostin, which blocks the membrane complex activation by Wnt, resulting in
      inhibition of bone formation. Studies of knockout and transgenic mouse models for
      Wnt pathway components have demonstrated that canonical signaling regulates most
      aspects of osteoblast physiology including commitment, differentiation, bone
      matrix formation/mineralization and apoptosis as well as coupling to
      osteoclastogenesis and bone resorption. Future studies in this rapidly growing
      area of research can possibly lead to the identification of targets of
      pharmacological intervention useful in the management of osteoporosis. In the
      present review we summarized the current knowledge related to the various
      components of the Wnt signaling pathway, the ways they cooperate in inducing and
      directing transcriptional functions as well as the interacting points with the
      TGFbeta superfamily. We also outlined a probable working integrating model of the
      mechanism of bone formation.

PMID- 18055420
TI  - Ghrelin and leptin levels in obese adolescents. Relationship with body fat and
      insulin resistance.
AB  - OBJECTIVE: Ghrelin and leptin levels are influenced by body fat (BF%), pubertal
      stage and possibly insulin resistance (IR). The aim of our study was: 1) To
      compare fasting ghrelin and leptin levels between obese and non-obese,
      adolescents, 2) to investigate possible correlations of these hormones with BF %,
      as well as IR. DESIGN: Twenty obese insulin resistant (IR) adolescents, twenty
      obese non IR (NIR) and fifteen healthy non-obese, age-matched adolescents were
      studied. In all participants, height, weight, body mass index (BMI) and BF % were
      measured. Fasting glucose, insulin, ghrelin and leptin levels were determined. IR
      was assessed using HOMA-IR index. RESULTS: BMI, BF %, insulin and HOMA-IR values
      were positively correlated with leptin and negatively with ghrelin levels. A
      negative correlation between circulating leptin and ghrelin levels was found. A
      suggestive positive correlation between leptin levels and BF %, independent of
      BMI, was also observed (P=0.075). Ghrelin levels were significantly correlated
      with insulin levels and HOMA-IR, independent of BMI (P=0.077). CONCLUSIONS:
      Obesity and IR may play an important role in the release of ghrelin as well as in
      the negative correlation between ghrelin and leptin.

PMID- 18055421
TI  - Recombinant human thyroid stimulating hormone does not acutely change serum
      osteoprotegerin and soluble receptor activator of nuclear factor-kappaBeta ligand
      in patients under evaluation for differentiated thyroid carcinoma.
AB  - OBJECTIVE: Some extra-thyroid actions of thyroid stimulating hormone (TSH), such
      as an in vitro action on bone, have been described. Our aim was to evaluate in
      vivo the acute effect of a recombinant human TSH (rhTSH)-induced TSH surge on
      Osteoprotegerin (OPG) and receptor activator of the nuclear factor-kappaBeta
      (RANK-L) levels in patients under levo-thyroxine (L-T4) therapy. DESIGN: 24
      patients with differentiated thyroid carcinoma (DTC) were studied. Standard rhTSH
      testing was performed. OPG, RANK-L, TSH, thyroid hormones, thyroglobulin and
      several parameters of bone metabolism were evaluated. RESULTS: Baseline OPG and
      RANK-L levels were in the range of our reference population. An inverse
      correlation between OPG and spinal Z-score (p=0.029) and between RANK-L and age
      (p=0.018) or urinary calcium/creatinine ratio (p=0.011) was detected. After rhTSH
      administration, a significant (p<0.001) increase in TSH was found. No significant
      increase in OPG or RANK-L levels after rhTSH was observed. No correlation was
      detected between TSH peak value after rhTSH and maximal percentage change in OPG
      or RANK-L. A slight increase in urinary cross-links after rhTSH was found.
      CONCLUSIONS: In a small group of subjects with a history of DTC on L-T4 regimen,
      our study did not support an acute direct effect of TSH on OPG and RANK-L.

PMID- 18055422
TI  - Stimulation of the hypothalamic-pituitary-adrenal axis with corticotropin
      releasing hormone in patients with psoriasis.
AB  - OBJECTIVE: Psychocutaneous diseases constitute a large proportion of
      psychosomatic disorders, with psoriasis being one of the most typical cases.
      Though alteration of Hypothalamic-Pituitary-Adrenal (HPA) axis function has been
      suggested as underlying several psychiatric disorders and psychosomatic diseases,
      there is little evidence of reduced response of the HPA axis in psoriasis after
      psychosocially induced laboratory stress. The aim of the study was to investigate
      any alteration of the neuroendocrine profile of psoriatic patients. DESIGN: The
      psoriatic patients (n=24) and the same number of matched controls underwent a CRH
      test which consisted of 100 microg h-CRH IV infusion and drawing of blood samples
      at 0 min and at 15, 30 and 60 min post h-CRH for measurement of plasma ACTH and
      cortisol concentration. RESULTS: Mean plasma ACTH and cortisol levels in both
      groups increased during the 60-min CRH test without significant difference. The
      total secretion of plasma ACTH and serum cortisol estimated as Area Under the
      Curve did not show significant difference between the groups either. CONCLUSIONS:
      Contrary to previous studies no particular neuroendocrine profile of HPA axis
      responsiveness was identified in psoriatic patients.

PMID- 18055423
TI  - Ghrelin and the enteroinsular axis in healthy men.
AB  - OBJECTIVE: Ghrelin, a potent stimulator of GH secretion, also acts as an
      orexigenic hormone. Plasma ghrelin levels rise before meals with postprandial
      reduction, suggesting that circulating levels of enteroinsular hormones might
      influence ghrelin secretion. AIM: The aim of this study was to evaluate the
      effects of ghrelin on enteroinsular hormones in healthy men. DESIGN: Three tests
      were performed on 3 different days in 6 healthy men: On the first day, saline was
      infused from 0-120 minutes followed by a ghrelin bolus (1 microg/kg)
      administration (Test 1); on the second experimental day, GHRH was administered at
      0 min, and a ghrelin bolus was given at 120 min (Test 2); on the third
      experimental day, GHRP-6 was administered at 0 min, followed by a ghrelin bolus
      at 120 min (Test 3). Plasma glucose, insulin, proinsulin, C-Peptide Glucagone
      Like Peptide one (GLP-1) determined at 0, 15, 30, 60, 90, and 120 min of the test
      period. RESULTS: There was a significant increase in AUC glucose (526.41+/-22.91
      mmol . ml(-1) . min vs. 566.37+/-15.64 mmol . ml(-1) . min; p<0.05) and AUC
      insulin (756.25+/-107.56 mU . ml(-1) . min vs. 981.62+/-180.32 mU . ml(-1) . min;
      p<0.05) and a significant decrease in AUC GLP-1 (2346.87+/-874.28 pmol . ml(-1) .
      min vs. 1769.5+/-784 pmol . ml(-1) . min; p<0.05) after ghrelin administration in
      Test 1 compared to Test 3. There was a mild but non-significant increase in AUC
      for insulin, proinsulin, and C-Peptide and a mild reduction in AUC GLP-1 after
      every ghrelin administration. CONCLUSION: There was no evidence of a direct
      effect of ghrelin administration on enteroinsular hormone levels in this study.
      However, ghrelin may potentiate the glucose-insulin stimulatory effects of GHRP
      6. More studies should be carried out for further evaluation of ghrelin
      enteroinsular hormones interplay.

PMID- 18055424
TI  - The alteration of serum soluble CD40 ligand levels in overt and subclinical
      hypothyroidism.
AB  - OBJECTIVE: There is controversy as to whether hypothyroidism increases
      cardiovascular risk. The effect of levothyroxine on the cardiovascular risk
      profile is also unclear. Recent studies suggest that there is evidence of
      inflammation and endothelial dysfunction in hypothyroidism. Soluble CD40 ligand
      (sCD40L) is a protein expressed mainly by activated platelets which have been
      found to be associated with cardiovascular events. The aim of our study was to
      investigate serum sCD40L levels and the effect of levothyroxine replacement on
      sCD40L levels in overt and subclinical hypothyroidism. DESIGN: We assessed lipid
      profile, serum sCD40L and hsCRP levels in 21 overt and 22 subclinical hypothyroid
      age-matched female patients with chronic autoimmune thyroiditis at baseline and
      one month after achieving euthyroidism by levothyroxine replacement, and compared
      them with the data from 22, age-matched, healthy controls. RESULTS: Overt and
      subclinical hypothyroid patients had decreased sCD40L levels compared to age
      matched controls. The patients with subclinical hypothyroidism had slightly
      increased hsCRP levels, but the result was not statistically significant. In
      multiple regression analysis, FT3 and FT4 were found to be independent predictors
      of sCD40L levels. After levothyroxine replacement, serum sCD40L levels increased
      significantly in the patients with overt hypothyroidism. Although an increase was
      also observed in the subclinical hypothyroid group, it was not statistically
      significant. Levothyroxine replacement had no significant effect on hsCRP levels
      in the patients with overt hypothyroidism. However, the subjects with subclinical
      hypothyroidism showed a significant reduction in hsCRP levels after
      levothyroxine. CONCLUSION: The values of sCD40L and hsCRP in our study suggest
      that inflammatory pathways are complex and may be affected by different factors
      in hypothyroidism.

PMID- 18055425
TI  - Normal lumbar bone mineral density in optimally treated children and young
      adolescents with beta-thalassaemia major.
AB  - OBJECTIVE: Osteopenia/osteoporosis of multi-factorial pathogenetic mechanism is
      reported to be a significant cause of morbidity in adult patients with beta
      thalassaemia major. Even in young patients, decreased Bone Mineral Density (BMD)
      values are a consistent finding in the literature. This study was performed in
      order to assess BMD in children and young adults with beta-thalassaemia major,
      regularly transfused and sufficiently chelated, along with auxological, clinical
      and laboratory parameters. DESIGN: Thirty-five young thalassaemic patients (19 F,
      16 M, aged 5-20 yr) were studied. Lumbar BMD was assessed by dual X-ray
      absorptiometry (DXA) and Z-scores were calculated according to bone density
      values using age- and sex-matched normal population. None of the patients
      presented with clinical or laboratory signs of endocrinopathy and none was
      receiving hormonal replacement therapy. RESULTS: All BMD Z-scores were within
      normal range, with a mean Z-score of 0.42 for girls and -0.41 for boys
      (statistically significant gender difference, p=0.018). When correlated with age,
      a decline in Z-scores was observed, indicating a delay in bone mass acquisition
      with advancing age in the thalassaemic group compared to controls. CONCLUSIONS:
      Optimal conventional treatment prevents the manifestation of
      osteopenia/osteoporosis during the first two decades of life in patients with
      beta-thalassaemia major. However, close surveillance with regular screening,
      preventive intervention and early management of possible endocrine complications
      are essential in order to secure normal bone health during adulthood and improve
      quality of life in the thalassaemic population.

PMID- 18055426
TI  - Tadeus Reichstein, co-winner of the Nobel Prize for Physiology or Medicine: on
      the occasion of the 110th anniversary of his birth in Poland.
AB  - Tadeus Reichstein (1897-1996) was the first scientist born in Poland to receive
      the Nobel Prize in Medicine or Physiology (1950) for the "discovery of hormones
      of the adrenal cortex, their structure and biological effects", as stated by the
      Nobel Prize Committee. His family being deeply devoted to Polish cultural and
      historical heritage, his first name was given to him after Tadeus Kosciuszko, a
      chief commander of the 18th century Polish uprising named the Kosciuszko
      Insurrection. As a child, he emigrated with his family to Switzerland, where he
      was much later to become involved in numerous research studies on steroids on an
      international scale. It was Tadeus Reichstein who isolated and synthesized
      desoxycorticosterone, which still remains the drug of first choice in the
      treatment of Addison's disease. Additionally, thanks to his strategy for the mass
      production of Vitamin C, the cost of this agent was drastically reduced thus
      enabling its widespread therapeutic use. In our divided world so often torn by
      tremendous conflicts, there is a great need to both remember and commemorate such
      distinguished people as Tadeus Reichstein who, despite the apparent "borders"
      between different nationalities and cultures, have demonstrated through their
      work the huge need for harmonious collaboration in the development of science.

PMID- 18055427
TI  - Biophysical controls on rhizospheric and heterotrophic components of soil
      respiration in a boreal black spruce stand.
AB  - We conducted a root-exclusion experiment in a 125-year-old boreal black spruce
      (Picea mariana (Mill.) BSP) stand in 2004 to quantify the physical and biological
      controls on temporal dynamics of the rhizospheric (R(r)) and heterotrophic (R(h))
      components of soil respiration (R(s)). Annual R(r), R(h) and estimated moss
      respiration were 285, 269 and 57 g C m(-2) year(-1), respectively, which
      accounted for 47, 44 and 9% of R(s) (611 g C m(-2) year(-1)), respectively. A
      gradual transition from R(h)-dominated (winter, spring and fall) to R(r)
      dominated (summer) respiration was observed during the year. Soil thawing in
      spring and the subsequent increase in soil water content (theta) induced a small
      and sustained increase in R(h) but had no effect on R(r). During the remainder of
      the growing season, no effect of theta was observed on either component of R(s).
      Both components increased exponentially with soil temperature (T(s)) during the
      growing season, but R(r) showed greater temperature sensitivity than R(h) (Q(10)
      of 4.0 and 3.0, respectively). Temperature-normalized variations in R(r) were
      highly correlated with eddy covariance estimates of gross ecosystem
      photosynthesis, and the correlation was greatest when R(r) was lagged by 24 days.
      Within diurnal cycles, variations in T(s) were highly coupled to variations in
      R(h) but were significantly decoupled from R(r). The patterns observed at both
      time scales strongly suggest that the flow of photosynthates to the rhizosphere
      is a key driver of belowground respiration processes but that photosynthate
      supply may control these processes in several ways.

PMID- 18055428
TI  - Responses of Acer saccharum canopy trees and saplings to P, K and lime additions
      under high N deposition.
AB  - Heavy atmospheric nitrogen (N) deposition has been associated with altered
      nutrient cycling, and even N saturation, in forest ecosystems previously thought
      to be N-limited. This observation has prompted application to such forests of non
      N mineral nutrients as a mitigation measure. We examined leaf gas-exchange, leaf
      chemistry and leaf and shoot morphological responses of Acer saccharum Marsh.
      saplings and mature trees to experimental additions of non-nitrogenous mineral
      nutrients (dolomitic lime, phosphorus + potassium (P + K) and lime plus P + K)
      over 2 years in the Haliburton region of central Ontario, which receives some of
      the largest annual N inputs in North America. Nutrients were adsorbed in the
      mineral soil and taken up by A. saccharum trees within 1 year of fertilizer
      application; however, contrary to expectation, liming had no effect on soil P
      availability. Saplings and canopy trees showed significant responses to both P +
      K fertilization and liming, including increased foliar nutrient concentration,
      leaf size and shoot extension growth; however, no treatment effects on leaf gas
      exchange parameters were detected. Increases in shoot extension preceded
      increases in diameter growth in saplings and canopy trees. Vector analysis of
      shoot extension growth and nutrient content was consistent with sufficiency of N
      but marked limitation of P, with co-limitation by calcium (Ca) in saplings and by
      Ca, Mg and K in canopy trees.

PMID- 18055429
TI  - Retranslocation of foliar nutrients in evergreen tree species planted in a
      Mediterranean environment.
AB  - Internal nutrient recycling through retranslocation (resorption) is important for
      meeting the nutrient demands of new tissue production in trees. We conducted a
      comparative study of nutrient retranslocation from leaves of five tree species
      from three genera grown in plantation forests for commercial or environmental
      purposes in southern Australia--Acacia mearnsii De Wild., Eucalyptus globulus
      Labill., E. fraxinoides H. Deane & Maiden, E. grandis W. Hill ex Maiden and Pinus
      radiata D. Don. Significant amounts of nitrogen, phosphorus and potassium were
      retranslocated during three phases of leaf life. In the first phase,
      retranslocation occurred from young leaves beginning 6 months after leaf
      initiation, even when leaves were physiologically most active. In the second
      phase, retranslocation occurred from mature green leaves during their second
      year, and in the third phase, retranslocation occurred during senescence before
      leaf fall. Nutrient retranslocation occurred mainly in response to new shoot
      production. The pattern of retranslocation was remarkably similar in the leaves
      of all study species (and in the phyllodes of Casuarina glauca Sieber ex
      Spreng.), despite their diverse genetics, leaf forms and growth rates. There was
      no net retranslocation of calcium in any of the species. The amounts of nutrients
      at the start of each pre-retranslocation phase had a strong positive relationship
      with the amounts subsequently retranslocated, and all species fitted a common
      relationship. The percentage reduction in concentration or content
      (retranslocation efficiency) at a particular growth phase is subject to many
      variables, even within a species, and is therefore not a meaningful measure of
      interspecific variation. It is proposed that the pattern of retranslocation and
      its governing factors are similar among species in the absence of interspecies
      competition for growth and crown structure which occurs in mixed species stands.

PMID- 18055430
TI  - Biophysical constraints on leaf expansion in a tall conifer.
AB  - The physiological mechanisms responsible for reduced extension growth as trees
      increase in height remain elusive. We evaluated biophysical constraints on leaf
      expansion in old-growth Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) trees.
      Needle elongation rates, plastic and elastic extensibility, bulk leaf water
      (Psi(L)) and osmotic (Psi(pi)) potential, bulk tissue yield threshold and final
      needle length were characterized along a height gradient in crowns of > 50-m-tall
      trees during the period between bud break and full expansion (May to June).
      Although needle length decreased with increasing height, there was no height
      related trend in leaf plastic extensibility, which was highest immediately after
      bud break (2.9%) and declined rapidly to a stable minimum value (0.3%) over a 3
      week period during which leaf expansion was completed. There was a significant
      positive linear relationship between needle elongation rates and plastic
      extensibility. Yield thresholds were consistently lower at the upper and middle
      crown sampling heights. The mean yield threshold across all sampling heights was
      0.12 +/- 0.03 MPa on June 8, rising to 0.34 +/- 0.03 MPa on June 15 and 0.45 +/-
      0.05 MPa on June 24. Bulk leaf Psi(pi) decreased linearly with increasing height
      at a rate of 0.004 MPa m(-1) during the period of most rapid needle elongation,
      but the vertical osmotic gradient was not sufficient to fully compensate for the
      0.015 MPa m(-1) vertical gradient in Psi(L), implying that bulk leaf turgor
      declined at a rate of about 0.011 MPa m(-1) increase in height. Although height
      dependent reductions in turgor appeared to constrain leaf expansion, it is
      possible that the impact of reduced turgor was mitigated by delayed phenological
      development with increasing height, which resulted in an increase with height in
      the temperature during leaf expansion.

PMID- 18055431
TI  - Seasonal carbohydrate storage and mobilization in bearing and non-bearing
      pistachio (Pistacia vera) trees.
AB  - We analyzed annual carbohydrate storage and mobilization of bearing ("on") and
      non-bearing ("off") 'Kerman' pistachio (Pistacia vera L.) trees growing on three
      different rootstocks. On all rootstocks, carbohydrate storage in shoots and
      branches of "on" and "off" trees was lowest following the spring growth flush. In
      "off" trees, stored carbohydrates increased and remained high after the initial
      growth flush. In "on" trees, stem carbohydrates increased temporarily in early
      summer, but were mobilized in mid-season during kernel fill, and then increased
      again after nut harvest. During the dormant season, the only substantial
      differences in carbohydrate storage between previously "on" and "off" trees were
      found in the roots of the weakest rootstock. The annual carbohydrate storage and
      mobilization pattern in canopy branches of heavily cropped pistachio trees
      appeared to be driven by carbohydrate demands related to nut development and
      untempered by tree vigor. Mobilization of carbohydrates from current-season and 1
      and 2-year-old stem wood of "on" trees during the primary period of kernel fill
      corresponded with the period of inflorescence bud abscission. Thus, the alternate
      bearing pattern associated with inflorescence bud abscission in 'Kerman'
      pistachio may be a function of mid-season mobilization of stored carbohydrates in
      current-season stems resulting in stimulation of inflorescence bud abscission.

PMID- 18055432
TI  - Sucrose (JrSUT1) and hexose (JrHT1 and JrHT2) transporters in walnut xylem
      parenchyma cells: their potential role in early events of growth resumption.
AB  - In temperate woody species, the vegetative growth period is characterized by
      active physiological events (e.g., bud break), which require an adequate supply
      of soluble sugars imported in the xylem sap stream. One-year-old shoots of walnut
      (Juglans regia L. cv. 'Franquette') trees, which have an acrotonic branching
      pattern (only apical and distal vegetative buds burst), were used to study the
      regulation of xylem sugar transporters in relation to bud break. At the end of
      April (beginning of bud break), a higher xylem sap sucrose concentration and a
      higher active sucrose uptake by xylem parenchyma cells were found in the apical
      portion (bearing buds able to burst) than in the basal portion (bearing buds
      unable to burst) of the sample shoots. At the same time, xylem parenchyma cells
      of the apical portion of the shoots exhibited greater amounts of both transcripts
      and proteins of JrSUT1 (Juglans regia putative sucrose transporter 1) than those
      of the basal stem segment. Conversely, no pronounced difference was found for
      putative hexose transporters JrHT1 and JrHT2 (Juglans regia hexose transporters 1
      and 2). These findings demonstrate the high capacity of bursting vegetative buds
      to import sucrose. Immunological analysis revealed that sucrose transporters were
      localized in all parenchyma cells of the xylem, including vessel-associated
      cells, which are highly specialized in nutrient exchange. Taken together, our
      results indicate that xylem parenchyma sucrose transporters make a greater
      contribution than hexose transporters to the imported carbon supply of bursting
      vegetative buds.

PMID- 18055433
TI  - Age-related trends in red spruce foliar plasticity in relation to declining
      productivity.
AB  - Phenotypic plasticity in needle morphology with increasing tree size and age was
      investigated by comparing four age classes of red spruce (Picea rubens Sarg.)
      ranging from juvenile (3-12 years old) to mature (over 100 years old). With
      increase in tree age there were significant increases in leaf mass per unit area
      (LMA), mesophyll and vascular bundle area as a percentage of total needle cross
      sectional area, and stomatal density. Within the vascular bundle, both xylem
      cross-sectional area and tracheid lumen area increased significantly, whereas air
      space as a percentage of total cross-sectional area decreased. These
      morphological changes were associated with a significant decrease in
      photosynthetic capacity and stomatal conductance, and an increase in (13)C
      enrichment. Although both photosynthetic capacity and whole-tree conductance
      decreased significantly between age classes 3 and 12 years, they did not differ
      between age classes 53 and 127 years, even though needle (13)C enrichment was
      significantly greater in the 127-year age class. Thus there appear to be
      compensatory mechanisms that maintain photosynthetic capacity as trees increase
      in size and vascular complexity, which in red spruce and other species, may
      affect leaf hydraulic conductance. Although increased LMA may contribute to
      reduced photosynthetic capacity in red spruce, similar relationships are not seen
      in other conifers.

PMID- 18055434
TI  - Tree growth and management in Ugandan agroforestry systems: effects of root
      pruning on tree growth and crop yield.
AB  - Tree root pruning is a potential tool for managing belowground competition when
      trees and crops are grown together in agroforestry systems. We investigated the
      effects of tree root pruning on shoot growth and root distribution of Alnus
      acuminata (H.B. & K.), Casuarina equisetifolia L., Grevillea robusta A. Cunn. ex
      R. Br., Maesopsis eminii Engl. and Markhamia lutea (Benth.) K. Schum. and on
      yield of adjacent crops in sub-humid Uganda. The trees were 3 years old at the
      commencement of the study, and most species were competing strongly with crops.
      Tree roots were pruned 41 months after planting by cutting and back-filling a
      trench to a depth of 0.3 m, at a distance of 0.3 m from the trees, on one side of
      the tree row. The trench was reopened and roots recut at 50 and 62 months after
      planting. We assessed the effects on tree growth and root distribution over a 3
      year period, and crop yield after the third root pruning at 62 months. Overall,
      root pruning had only a slight effect on aboveground tree growth: height growth
      was unaffected and diameter growth was reduced by only 4%. A substantial amount
      of root regrowth was observed by 11 months after pruning. Tree species varied in
      the number and distribution of roots, and C. equisetifolia and M. lutea had
      considerably more roots per unit of trunk volume than the other species,
      especially in the surface soil layers. Casuarina equisetifolia and M. eminii were
      the tree species most competitive with crops and G. robusta and M. lutea the
      least competitive. Crop yield data provided strong evidence of the redistribution
      of root activity following root pruning, with competition increasing on the
      unpruned side of tree rows. Thus, one-sided root pruning will be useful in only a
      few circumstances.

PMID- 18055435
TI  - Carbon gain and bud physiology in Populus tremuloides and Betula papyrifera grown
      under long-term exposure to elevated concentrations of CO2 and O3.
AB  - Paper birch (Betula papyrifera Marsh.) and three trembling aspen clones (Populus
      tremuloides Michx.) were studied to determine if alterations in carbon gain in
      response to an elevated concentration of CO(2) ([CO(2)]) or O(3) ([O(3)]) or a
      combination of both affected bud size and carbohydrate composition in autumn, and
      early leaf development in the following spring. The trees were measured for gas
      exchange, leaf size, date of leaf abscission, size and biochemical
      characteristics of the overwintering buds and early leaf development during the
      8th-9th year of free-air CO(2) and O(3) exposure at the Aspen FACE site located
      near Rhinelander, WI. Net photosynthesis was enhanced 49-73% by elevated [CO(2)],
      and decreased 13-30% by elevated [O(3)]. Elevated [CO(2)] delayed, and elevated
      [O(3)] tended to accelerate, leaf abscission in autumn. Elevated [CO(2)]
      increased the ratio of monosaccharides to di- and oligosaccharides in aspen buds,
      which may indicate a lag in cold acclimation. The total carbon concentration in
      overwintering buds was unaffected by the treatments, although elevated [O(3)]
      decreased the amount of starch by 16% in birch buds, and reduced the size of
      aspen buds, which may be related to the delayed leaf development in aspen during
      the spring. Elevated [CO(2)] generally ameliorated the effects of elevated
      [O(3)]. Our results show that both elevated [CO(2)] and elevated [O(3)] have the
      potential to alter carbon metabolism of overwintering buds. These changes may
      cause carry-over effects during the next growing season.

PMID- 18055436
TI  - Traumatic resin ducts in Larix decidua stems impacted by debris flows.
AB  - Following mechanical injury, stems of many conifers produce tangential rows of
      traumatic resin ducts (TRDs), the distribution of which has been used to date
      geomorphic events. However, little is known about how far TRD formation extends
      tangentially and axially from the point of injury or what the time course of TRD
      appearance is. We analyzed 28 injuries in eight Larix decidua Mill. tree stems
      resulting from debris flows in October 2000 and November 2004. Injuries occurred
      outside the period of cambial activity, and TRD formation occurred in the first
      layers of the growth ring formed in the year following that of injury. The axial
      extent of TRD formation averaged 74 cm and was greater above the injury than
      below it. At the height of the wound center, TRDs extended horizontally to a mean
      of 18% of the stem circumference excluding that portion where the cambium had
      been destroyed. In subsequent growth rings, TRDs, if present, were confined
      mainly to the height of the center of injury. Both the vertical and horizontal
      extent of TRD formation was related to the injury size. Within growth rings, the
      position of TRD formation changed with increasing distance from the wound
      progressing from early earlywood to later portions of the growth ring.

PMID- 18055437
TI  - Predicting the decline in daily maximum transpiration rate of two pine stands
      during drought based on constant minimum leaf water potential and plant hydraulic
      conductance.
AB  - The effect of drought on forest water use is often estimated with models, but
      comprehensive models require many parameters, and simple models may not be
      sufficiently flexible. Many tree species, Pinus species in particular, have been
      shown to maintain a constant minimum leaf water potential above the critical
      threshold for xylem embolism during drought. In such cases, prediction of the
      relative decline in daily maximum transpiration rate with decreasing soil water
      content is relatively straightforward. We constructed a soil-plant water flow
      model assuming constant plant conductance and daily minimum leaf water potential,
      but variable conductance from soil to root. We tested this model against
      independent data from two sites: automatic shoot chamber data and sap flow
      measurements from a boreal Scots pine (Pinus sylvestris L.) stand; and sap flow
      measurements from a maritime pine (Pinus pinaster Ait.) stand. To focus on soil
      limitations to water uptake, we expressed daily maximum transpiration rate
      relative to the rate that would be obtained in wet soil with similar
      environmental variables. The comparison was successful, although the maritime
      pine stand showed carry-over effects of the drought that we could not explain.
      For the boreal Scots pine stand, daily maximum transpiration was best predicted
      by water content of soil deeper than 5 cm. A sensitivity analysis revealed that
      model predictions were relatively insensitive to the minimum leaf water
      potential, which can be accounted for by the importance of soil resistance of
      drying soil. We conclude that a model with constant plant conductance and minimum
      leaf water potential can accurately predict the decline in daily maximum
      transpiration rate during drought for these two pine stands, and that including
      further detail about plant compartments would add little predictive power, except
      in predicting recovery from severe drought.

PMID- 18055438
TI  - Annual and seasonal variations in photosynthetic capacity of Fagus crenata along
      an elevation gradient in the Naeba Mountains, Japan.
AB  - Canopy photosynthetic capacity, measured as leaf maximum carboxylation rate (V
      (cmax)), is a key factor in ecosystem gas exchange models applied at different
      scales. We report seasonal and interannual variations in V(cmax) of natural beech
      stands (Fagus crenata Blume) along an altitudinal gradient in the temperate
      climate zone of Japan. Estimates are based on 6 years of gas exchange
      measurements. Pronounced seasonal and interannual variations in V(cmax)
      normalized to 25 degrees C (V(c,25)) were found for sun leaves. The seasonal
      pattern of V(c,25) generally followed an inverse parabolic curve, with an
      increase in spring, peak values in the middle of the growth period and a decline
      in autumn. Leaf nitrogen concentration (N(l)) and leaf mass per area were
      significantly related to V(c,25) during spring and summer, but were unrelated in
      autumn when V(c,25) declined. Annual peak V(c,25) ranged from 40.1 to 97.0
      micromol m(-2) s(-1) and varied over as much as a twofold range at a particular
      site. Annual peak V(c,25) occurred about 28 days before annual peak N(l), with
      which it was poorly related. Our results show that it can be inappropriate to
      include constant values of photosynthetic parameters in ecosystem gas exchange
      models.

PMID- 18055439
TI  - Changes in petiole hydraulic properties and leaf water flow in birch and oak
      saplings in a CO2-enriched atmosphere.
AB  - Water relations in woody species are intimately related to xylem hydraulic
      properties. High CO(2) concentrations ([CO(2)]) generally decrease transpiration
      and stomatal conductance (g(s)), but there is little information about the effect
      of atmospheric [CO(2)] on xylem hydraulic properties. To determine the
      relationship between water flow and hydraulic structure at high [CO(2)], we
      investigated responses of sun and shade leaves of 4-year-old saplings of diffuse
      porous Betula maximowicziana Regel and ring-porous Quercus mongolica Fisch. ex
      Ledeb. ssp. crispula (Blume) Menitsky grown on fertile brown forest soil or
      infertile volcanic ash soil and exposed to 500 micromol CO(2) mol(-1) for 3
      years. Regardless of species and soil type, elevated [CO(2)] consistently
      decreased water flow (i.e., g(s) and leaf-specific hydraulic conductivity) and
      total vessel area of the petiole in sun leaves; however, it had no effect on
      these parameters in shade leaves, perhaps because g(s) of shade leaves was
      already low. Changes in water flow at elevated [CO(2)] were associated with
      changes in petiole hydraulic properties.

PMID- 18055440
TI  - Genotypic variation and phenotypic plasticity in the drought response of fine
      roots of European beech.
AB  - How temperate trees respond to drier summers, as predicted by climate change
      models for parts of Europe and eastern North America, will depend on the drought
      susceptibility of the root systems. We investigated the importance of the genetic
      constitution for the belowground drought response of European beech (Fagus
      sylvatica L.), in four populations from regions differing in precipitation (520
      970 mm year(-1)). Saplings were grown at ample (10 vol.%; well-watered) or
      reduced (5 vol.%; drought treatment) soil water content in the Gottingen Rhizolab
      Facility for two consecutive summers, and the responses of fine root biomass,
      root morphology, root depth distribution, and fine root production and turnover
      were investigated by a combined mini-rhizotron and harvest technique approach. In
      the drought treatment, total root mass per plant was reduced by 30-40% as a
      result of: (1) a reduction in median fine root lifespan by roughly 50% and hence
      an increase in fine root turnover; and (2) a 10-fold reduction in relative fine
      root growth rate (productivity per standing root biomass). The root:shoot ratio
      did not increase with drought. Although beech plants originating from drier
      climates tended to reduce their root biomass in response to drought less than
      those from wetter climates, analyses of variance revealed no significant
      influence of genotype on root mass, morphology, growth rate or turnover. However,
      most fine root traits showed marked differences between the well-watered and
      drought treatments. We conclude that beech saplings respond to summer drought
      primarily by shortening root lifespan, whereas root system structure and
      root:shoot carbon partitioning pattern are unaltered. Beech fine root growth and
      turnover exhibited high phenotypic plasticity, but genotypic variation was of
      minor importance. In contrast, genotype had a strong influence on leaf and shoot
      morphogenesis and growth.

PMID- 18055441
TI  - Climatic control of bud burst in young seedlings of nine provenances of Norway
      spruce.
AB  - Detailed knowledge of temperature effects on the timing of dormancy development
      and bud burst will help evaluate the impacts of climate change on forest trees.
      We tested the effects of temperature applied during short-day treatment, duration
      of short-day treatment, duration of chilling and light regime applied during
      forcing on the timing of bud burst in 1- and 2-year-old seedlings of nine
      provenances of Norway spruce (Picea abies (L.) Karst.). High temperature during
      dormancy induction, little or no chilling and low temperature during forcing all
      delayed dormancy release but did not prevent bud burst or growth onset provided
      the seedlings were forced under long-day conditions. Without chilling, bud burst
      occurred in about 20% of seedlings kept in short days at 12 degrees C, indicating
      that young Norway spruce seedlings do not exhibit true bud dormancy. Chilling
      hastened bud burst and removed the long photoperiod requirement, but the effect
      of high temperature applied during dormancy induction was observed even after
      prolonged chilling. Extension of the short-day treatment from 4 to 8 or 12 weeks
      hastened bud burst. The effect of treatments applied during dormancy development
      was larger than that of provenance; in some cases no provenance effect was
      detected, but in 1-year-old seedlings, time to bud burst decreased linearly with
      increasing latitude of origin. Differences among provenances were complicated by
      different responses of some origins to light conditions under long-day forcing.
      In conclusion, timing of bud burst in Norway spruce seedlings is significantly
      affected by temperature during bud set, and these effects are modified by
      chilling and environmental conditions during forcing.

PMID- 18055442
TI  - Reprogramming battle: Egg vs. Virus.

PMID- 18055443
TI  - Downregulation of multiple stress defense mechanisms during differentiation of
      human embryonic stem cells.
AB  - Evolutionary theory predicts that cellular maintenance, stress defense, and DNA
      repair mechanisms should be most active in germ line cells, including embryonic
      stem cells that can differentiate into germ line cells, whereas it would be
      energetically unfavorable to keep these up in mortal somatic cells. We tested
      this hypothesis by examining telomere maintenance, oxidative stress generation,
      and genes involved in antioxidant defense and DNA repair during spontaneous
      differentiation of two human embryonic stem cell lines. Telomerase activity was
      quickly downregulated during differentiation, probably due to deacetylation of
      histones H3 and H4 at the hTERT promoter and deacetylation of histone H3 at hTR
      promoter. Telomere length decreased accordingly. Mitochondrial superoxide
      production and cellular levels of reactive oxygen species increased as result of
      increased mitochondrial biogenesis. The expression of major antioxidant genes was
      downregulated despite this increased oxidative stress. DNA damage levels
      increased during differentiation, whereas expression of genes involved in
      different types of DNA repair decreased. These results confirm earlier data
      obtained during mouse embryonic stem cell differentiation and are in accordance
      with evolutionary predictions.

PMID- 18055444
TI  - Identification of a novel putative gastrointestinal stem cell and adenoma stem
      cell marker, doublecortin and CaM kinase-like-1, following radiation injury and
      in adenomatous polyposis coli/multiple intestinal neoplasia mice.
AB  - In the gut, tumorigenesis arises from intestinal or colonic crypt stem cells.
      Currently, no definitive markers exist that reliably identify gut stem cells.
      Here, we used the putative stem cell marker doublecortin and CaM kinase-like-1
      (DCAMKL-1) to examine radiation-induced stem cell apoptosis and adenomatous
      polyposis coli (APC)/multiple intestinal neoplasia (min) mice to determine the
      effects of APC mutation on DCAMKL-1 expression. Immunoreactive DCAMKL-1 staining
      was demonstrated in the intestinal stem cell zone. Furthermore, we observed
      apoptosis of the cells negative for DCAMKL-1 at 6 hours. We found DNA damage in
      all the cells in the crypt region, including the DCAMKL-1-positive cells. We also
      observed stem cell apoptosis and mitotic DCAMKL-1-expressing cells 24 hours after
      irradiation. Moreover, in APC/min mice, DCAMKL-1-expressing cells were negative
      for proliferating cell nuclear antigen and nuclear beta-catenin in normal
      appearing intestine. However, beta-catenin was nuclear in DCAMKL-1-positive cells
      in adenomas. Thus, nuclear translocation of beta-catenin distinguishes normal and
      adenoma stem cells. Targeting DCAMKL-1 may represent a strategy for developing
      novel chemotherapeutic agents.

PMID- 18055445
TI  - Constitutive expression of the ATP-binding cassette transporter ABCG2 enhances
      the growth potential of early human hematopoietic progenitors.
AB  - The ATP-binding cassette transporter, ABCG2, is a molecular determinant of the
      side population phenotype, which is enriched for stem and progenitor cells in
      various nonhematopoietic and hematopoietic tissues. ABCG2 is highly expressed in
      hematopoietic progenitors and silenced in differentiated hematopoietic cells,
      suggesting a role of ABCG2 in early hematopoiesis. To test whether ABCG2 is
      involved in human hematopoietic development, we retrovirally transduced umbilical
      cord blood-derived early hematopoietic cells and analyzed hematopoiesis in vitro
      and in vivo. ABCG2 increased the number of clonogenic progenitors in vitro,
      including the most primitive colony-forming unit-granulocyte, erythroid,
      macrophage, megakaryocyte, by twofold (n = 14; p < .0005). Furthermore, ABCG2
      induced a threefold increase in the replating capacity of primary colonies (n =
      9; p < .01). In addition, ABCG2 impaired the development of CD19+ lymphoid cells
      in vitro. In transplanted NOD/SCID mice, the ATP-binding cassette transporter
      decreased the number of human B-lymphoid cells, resulting in an inversion of the
      lymphoid/myeloid ratio. ABCG2 enhanced the proportion of CD34+ progenitor cells
      in vivo (n = 4; p < .05) and enhanced the most primitive human progenitor pool,
      as determined by limiting dilution competitive repopulating unit assay (p <
      .034). Our data characterize ABCG2 as a regulatory protein of early human
      hematopoietic development.

PMID- 18055446
TI  - Connexin expression and functional analysis of gap junctional communication in
      mouse embryonic stem cells.
AB  - Gap junctional intercellular communication (GJIC) has been suggested to be
      necessary for cellular proliferation and differentiation. We wanted to
      investigate the function of GJIC in mouse embryonic stem (ES) cells using
      pharmacological inhibitors or a genetic approach to inhibit the expression of
      connexins, that is, the subunit proteins of gap junction channels. For this
      purpose, we have analyzed all known connexin genes in mouse ES cells but found
      only three of them, Cx31, Cx43, and Cx45, to be expressed as proteins. We have
      demonstrated by coimmunoprecipitation that Cx31 and Cx43, as well as Cx43 and
      Cx45, probably form heteromeric gap junction channels, whereas Cx31 and Cx45 do
      not. The pharmacological inhibitors reduced GJIC between ES cells to
      approximately 3% and initiated apoptosis, suggesting an antiapoptotic effect of
      GJIC. In contrast to these results, reduction of GJIC to approximately 5% by
      decreased expression of Cx31 or Cx45 via RNA interference in homozygous Cx43
      deficient ES cells did not lead to apoptosis. Additional studies suggested that
      apoptotic death of ES cells and adult stem cells reported in the literature is
      likely due to a cytotoxic side effect of the inhibitors and not due to a decrease
      of GJIC. Using the connexin expression pattern in mouse ES cells, as determined
      in this study, multiple connexin-deficient ES cells can now be genetically
      engineered in which the level of GJIC is further decreased, to clarify whether
      the differentiation of ES cells is qualitatively or quantitatively compromised.

PMID- 18055447
TI  - Widespread nonhematopoietic tissue distribution by transplanted human progenitor
      cells with high aldehyde dehydrogenase activity.
AB  - Transplanted adult progenitor cells distribute to peripheral organs and can
      promote endogenous cellular repair in damaged tissues. However, development of
      cell-based regenerative therapies has been hindered by the lack of preclinical
      models to efficiently assess multiple organ distribution and difficulty defining
      human cells with regenerative function. After transplantation into beta
      glucuronidase (GUSB)-deficient NOD/SCID/mucopolysaccharidosis type VII mice, we
      characterized the distribution of lineage-depleted human umbilical cord blood
      derived cells purified by selection using high aldehyde dehydrogenase (ALDH)
      activity with CD133 coexpression. ALDH(hi) or ALDH(hi)CD133+ cells produced
      robust hematopoietic reconstitution and variable levels of tissue distribution in
      multiple organs. GUSB+ donor cells that coexpressed human leukocyte antigen (HLA
      A,B,C) and hematopoietic (CD45+) cell surface markers were the primary cell
      phenotype found adjacent to the vascular beds of several tissues, including islet
      and ductal regions of mouse pancreata. In contrast, variable phenotypes were
      detected in the chimeric liver, with HLA+/CD45+ cells demonstrating robust GUSB
      expression adjacent to blood vessels and CD45-/HLA- cells with diluted GUSB
      expression predominant in the liver parenchyma. However, true nonhematopoietic
      human (HLA+/CD45-) cells were rarely detected in other peripheral tissues,
      suggesting that these GUSB+/HLA-/CD45- cells in the liver were a result of
      downregulated human surface marker expression in vivo, not widespread seeding of
      nonhematopoietic cells. However, relying solely on continued expression of cell
      surface markers, as used in traditional xenotransplantation models, may
      underestimate true tissue distribution. ALDH-expressing progenitor cells
      demonstrated widespread and tissue-specific distribution of variable cellular
      phenotypes, indicating that these adult progenitor cells should be explored in
      transplantation models of tissue damage.

PMID- 18055448
TI  - Distinct effects of the soluble versus membrane-bound forms of the notch ligand
      delta-4 on human CD34+CD38low cell expansion and differentiation.
AB  - Although Notch ligands are considered to activate signaling through direct cell
      cell contact, the existence of soluble forms has been demonstrated. However,
      their roles remain controversial: soluble forms have been reported to mimic the
      biological activity of membrane-bound form, whereas other studies rather
      suggested an antagonistic activity toward their full-length counterparts. We
      previously observed that membrane-bound Delta4-expressing S17 stroma (mbD4/S17)
      reduced human CD34+CD38(low) cell proliferation and favored self-renewal. Here,
      we assessed the effects of a soluble form of Delta4 (solD4) by exposing
      CD34+CD38(low) cells to S17 feeders engineered to express solD4 (solD4/S17). In
      contrast to mbD4/S17, (a) solD4/S17 increased 10-fold cell production after 2
      weeks, through enhanced cell proliferation, and (b) it did not preserve colony
      forming cell and long-term culture-initiating cell potential of output CD34+
      cells. mbD4 and solD4 appeared to also differ in their signaling. Indeed, mbD4,
      but not solD4, strongly activated both CSL (the nuclear mediator of Notch
      signaling) in Hela cells overexpressing Notch1 and transcription of some classic
      Notch target genes in CD34+CD38(low) cells. Furthermore, both biological effects
      and CSL activation elicited by mbD4 were strictly dependent upon the gamma
      secretase complex, whereas solD4 enhanced cell expansion in a partially gamma
      secretase-independent manner. Altogether, these results suggest that part of
      solD4 activity did not rely upon canonical Notch pathway.

PMID- 18055449
TI  - Cell-cell signaling through NOTCH regulates human embryonic stem cell
      proliferation.
AB  - Unlike pluripotent mouse embryonic stem (ES) cells, human ES cells and their
      malignant equivalents, embryonal carcinoma (EC) cells, require close cell-cell
      contact for efficient growth. Signaling through the NOTCH receptor, initiated by
      interaction with ligands of the DELTA/JAGGED family expressed on neighboring
      cells, plays a role in regulating the self-renewal of several stem cell systems.
      Members of the NOTCH and DELTA/JAGGED families are expressed by human EC and ES
      cells, and we have therefore investigated the possible role of NOTCH in the
      maintenance of these cells. Cleavage of both NOTCH1 and NOTCH2 to yield the
      intracellular domain responsible for the canonical signaling pathway of NOTCH was
      detected in several human EC and ES cell lines, suggesting that NOTCH signaling
      is active. Furthermore, the proliferation of human EC cells, as well as the
      expression of several downstream NOTCH target genes, was markedly reduced after
      small interfering RNA knockdown of NOTCH1, NOTCH2, and the canonical effector CBF
      1 or after blocking NOTCH signaling with the gamma-secretase inhibitor L-685,458.
      The inhibitor also caused a reduction in the growth of human ES cells, although
      without evidence of differentiation. The results indicate that cell-cell
      signaling through the NOTCH system provides a critical cue for the proliferation
      of human EC and ES cell in vitro.

PMID- 18055450
TI  - Characterization of adult prostatic progenitor/stem cells exhibiting self-renewal
      and multilineage differentiation.
AB  - Demonstration of the hallmarks of stem cells, self-renewal and multilineage
      differentiation, is a challenge that has not been met for numerous tissues
      postulated to possess adult stem cells, including prostate tissue. Using a
      defined medium, we reproducibly isolated and maintained adult mouse prostatic
      cells with characteristics of progenitor/stem cells. Clonal populations of cells
      demonstrated tissue-specific multilineage differentiation by their ability to
      generate organized prostatic ductal structures in vivo, with luminal and basal
      cell layers, when grafted under the renal capsules of mice in the presence of
      fetal rat urogenital mesenchyme. Complete differentiation was demonstrated by the
      expression and secretion of terminally differentiated prostatic secretory
      products into the lumens. Self-renewal was demonstrated by serial transplantation
      of clonal populations that generated fully differentiated ductal structures in
      vivo. In vitro, undifferentiated cells expressed markers associated with prostate
      stem cells, including Sca 1 and CD49f, as well as basal cell markers (p63 and
      cytokeratins 5 and 14) and, at a low level, luminal cell markers (androgen
      receptor and cytokeratins 8 and 18). When grafted and allowed to differentiate in
      the presence of fetal urogenital mesenchyme, the cells differentiated into
      luminal cells and basal cells with more restricted protein expression patterns.
      These studies are the first to report a reproducible system to assess adult
      prostatic progenitor/stem cells.

PMID- 18055451
TI  - Fluorophore-conjugated iron oxide nanoparticle labeling and analysis of
      engrafting human hematopoietic stem cells.
AB  - The use of nanometer-sized iron oxide particles combined with molecular imaging
      techniques enables dynamic studies of homing and trafficking of human
      hematopoietic stem cells (HSC). Identifying clinically applicable strategies for
      loading nanoparticles into primitive HSC requires strictly defined culture
      conditions to maintain viability without inducing terminal differentiation. In
      the current study, fluorescent molecules were covalently linked to dextran-coated
      iron oxide nanoparticles (Feridex) to characterize human HSC labeling to monitor
      the engraftment process. Conjugating fluorophores to the dextran coat for
      fluorescence-activated cell sorting purification eliminated spurious signals from
      nonsequestered nanoparticle contaminants. A short-term defined incubation
      strategy was developed that allowed efficient labeling of both quiescent and
      cycling HSC, with no discernable toxicity in vitro or in vivo. Transplantation of
      purified primary human cord blood lineage-depleted and CD34(+) cells into
      immunodeficient mice allowed detection of labeled human HSC in the recipient
      bones. Flow cytometry was used to precisely quantitate the cell populations that
      had sequestered the nanoparticles and to follow their fate post-transplantation.
      Flow cytometry endpoint analysis confirmed the presence of nanoparticle-labeled
      human stem cells in the marrow. The use of fluorophore-labeled iron oxide
      nanoparticles for fluorescence imaging in combination with flow cytometry allows
      evaluation of labeling efficiencies and homing capabilities of defined human HSC
      subsets.

PMID- 18055452
TI  - The PsbS protein controls the organization of the photosystem II antenna in
      higher plant thylakoid membranes.
AB  - The PsbS subunit of photosystem II (PSII) plays a key role in nonphotochemical
      quenching (NPQ), the major photoprotective regulatory mechanism in higher plant
      thylakoid membranes, but its mechanism of action is unknown. Here we describe
      direct evidence that PsbS controls the organization of PSII and its light
      harvesting system (LHCII). The changes in chlorophyll fluorescence amplitude
      associated with the Mg(2+)-dependent restacking of thylakoid membranes were
      measured in thylakoids prepared from wild-type plants, a PsbS-deficient mutant
      and a PsbS overexpresser. The Mg(2+) requirement and sigmoidicity of the
      titration curves for the fluorescence rise were negatively correlated with the
      level of PsbS. Using a range of PsbS mutants, this effect of PsbS was shown not
      to depend upon its efficacy in controlling NPQ, but to be related only to protein
      concentration. Electron microscopy and fluorescence spectroscopy showed that this
      effect was because of enhancement of the Mg(2+)-dependent re-association of PSII
      and LHCII by PsbS, rather than an effect on stacking per se. In the presence of
      PsbS the LHCII.PSII complex was also more readily removed from thylakoid
      membranes by detergent, and the level of PsbS protein correlated with the
      amplitude of the psi-type CD signal originating from features of LHCII.PSII
      organization. It is proposed that PsbS regulates the interaction between LHCII
      and PSII in the grana membranes, explaining how it acts as a pH-dependent trigger
      of the conformational changes within the PSII light harvesting system that result
      in NPQ.

PMID- 18055453
TI  - A third zinc-binding domain of human poly(ADP-ribose) polymerase-1 coordinates
      DNA-dependent enzyme activation.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a chromatin-associated enzyme with
      multiple cellular functions, including DNA repair, transcriptional regulation,
      and cell signaling. PARP-1 has a modular architecture with six independent
      domains comprising the 113-kDa polypeptide. Two zinc finger domains at the N
      terminus of PARP-1 bind to DNA and thereby activate the catalytic domain situated
      at the C terminus of the enzyme. The tight coupling of DNA binding and catalytic
      activities is critical to the cellular regulation of PARP-1 function; however,
      the mechanism for coordinating these activities remains an unsolved problem.
      Here, we demonstrate using spectroscopic and crystallographic analysis that human
      PARP-1 has a third zinc-binding domain. Biochemical mutagenesis and deletion
      analysis indicate that this region mediates interdomain contacts important for
      DNA-dependent enzyme activation. The crystal structure of the third zinc-binding
      domain reveals a zinc ribbon fold and suggests conserved residues that could form
      interdomain contacts. The new zinc-binding domain self-associates in the crystal
      lattice to form a homodimer with a head-totail arrangement. The structure of the
      homodimer provides a scaffold for assembling the activated state of PARP-1 and
      suggests a mechanism for coupling the DNA binding and catalytic functions of PARP
      1.

PMID- 18055454
TI  - Sphingosine kinase 1 is up-regulated during hypoxia in U87MG glioma cells. Role
      of hypoxia-inducible factors 1 and 2.
AB  - Sphingosine 1-phosphate (S1P), a sphingolipid metabolite that plays an important
      role in the regulation of cell survival, growth, migration, and angiogenesis,
      acts both inside the cells and as an extracellular mediator through binding to
      five G protein-coupled receptors (S1P(1-5)). Sphingosine kinase 1 (SK1), the
      enzyme responsible for S1P production, is overexpressed in many solid tumors,
      including gliomas. One common feature of these tumors is the presence of "hypoxic
      regions," characterized by cells expressing high levels of hypoxia-inducible
      factors HIF-1alpha and HIF-2alpha, two transcription regulators that modulate the
      levels of proteins with crucial roles in tumor progression. So far, nothing is
      known about the role and the regulation of SK1 during tumor-induced hypoxia or
      about SK1 regulation and HIFs. Here we investigated the role of HIF-1alpha and
      HIF-2alpha in the regulation of SK1 during hypoxic stress in glioma-derived U87MG
      cells. We report that hypoxia increases SK1 mRNA levels, protein expression, and
      enzyme activity, followed by intracellular S1P production and S1P release.
      Interestingly, knockdown of HIF-2alpha by small interfering RNA abolished the
      induction of SK1 and the production of extracellular S1P after CoCl(2) treatment,
      whereas HIF-1alpha small interfering RNA resulted in an increase of HIF-2alpha
      and of SK1 protein levels. Moreover, using chromatin immunoprecipitation
      analysis, we demonstrate that HIF-2alpha binds the SK1 promoter. Functionally, we
      demonstrate that conditioned medium from hypoxia-treated tumor cells results in
      neoangiogenesis in human umbilical vein endothelial cells in a S1P receptor
      dependent manner. These studies provide evidence of a link between S1P production
      as a potent angiogenic agent and the hypoxic phenotype observed in many tumors.

PMID- 18055455
TI  - Severe acute respiratory syndrome-associated coronavirus nucleocapsid protein
      interacts with Smad3 and modulates transforming growth factor-beta signaling.
AB  - Severe acute respiratory syndrome (SARS) is an acute infectious disease with
      significant mortality. A typical clinical feature associated with SARS is
      pulmonary fibrosis and the associated lung failure. However, the underlying
      mechanism remains elusive. In this study, we demonstrate that SARS-associated
      coronavirus (SARS-CoV) nucleocapsid (N) protein potentiates transforming growth
      factor-beta (TGF-beta)-induced expression of plasminogen activator inhibitor-1
      but attenuates Smad3/Smad4-mediated apoptosis of human peripheral lung epithelial
      HPL1 cells. The promoting effect of N protein on the transcriptional responses of
      TGF-beta is Smad3-specific. N protein associates with Smad3 and promotes Smad3
      p300 complex formation while it interferes with the complex formation between
      Smad3 and Smad4. These findings provide evidence of a novel mechanism whereby N
      protein modulates TGF-beta signaling to block apoptosis of SARS-CoV-infected host
      cells and meanwhile promote tissue fibrosis. Our results reveal a novel mode of
      Smad3 action in a Smad4-independent manner and may lead to successful strategies
      for SARS treatment by targeting the TGF-beta signaling molecules.

PMID- 18055456
TI  - Bivalent binding to gammaA/gamma'-fibrin engages both exosites of thrombin and
      protects it from inhibition by the antithrombin-heparin complex.
AB  - Thrombin exosite 1 binds the predominant gamma(A)/gamma(A)-fibrin form with low
      affinity. A subpopulation of fibrin molecules, gamma(A)/gamma'-fibrin, has an
      extended COOH terminus gamma'-chain that binds exosite 2 of thrombin. Bivalent
      binding to gamma(A)/gamma'-fibrin increases the affinity of thrombin 10-fold, as
      determined by surface plasmon resonance. Because of its higher affinity, thrombin
      dissociates 7-fold more slowly from gamma(A)/gamma'-fibrin clots than from
      gamma(A)/gamma(A)-fibrin clots. After 24 h of washing, however, both
      gamma(A)/gamma'- and gamma(A)/gamma(A)-fibrin clots generate fibrinopeptide A
      when incubated with fibrinogen, indicating the retention of active thrombin.
      Previous studies demonstrated that heparin heightens the affinity of thrombin for
      fibrin by simultaneously binding to fibrin and exosite 2 on thrombin to generate
      a ternary heparin-thrombin-fibrin complex that protects thrombin from inhibition
      by antithrombin and heparin cofactor II. In contrast, dermatan sulfate does not
      promote ternary complex formation because it does not bind to fibrin. Heparin
      catalyzed rates of thrombin inhibition by antithrombin were 5-fold slower in
      gamma(A)/gamma'-fibrin clots than they were in gamma(A)/gamma(A)-fibrin clots.
      This difference reflects bivalent binding of thrombin to gamma(A)/gamma'-fibrin
      because (a) it is abolished by addition of a gamma'-chain-directed antibody that
      blocks exosite 2-mediated binding of thrombin to the gamma'-chain and (b) the
      dermatan sulfate-catalyzed rate of thrombin inhibition by heparin cofactor II
      also is lower with gamma(A)/gamma'-fibrin than with gamma(A)/gamma(A)-fibrin
      clots. Thus, bivalent binding of thrombin to gamma(A)/gamma'-fibrin protects
      thrombin from inhibition, raising the possibility that gamma(A)/gamma'-fibrin
      serves as a reservoir of active thrombin that renders thrombi thrombogenic.

PMID- 18055457
TI  - Glycogen synthase kinase 3beta interacts with and phosphorylates the spindle
      associated protein astrin.
AB  - Emerging evidence shows that glycogen synthase kinase 3beta (GSK3beta) is
      involved in mitotic division and that inhibiting of GSK3beta kinase activity
      causes defects in spindle microtubule length and chromosome alignment. However,
      the purpose of GSK3beta involvement in spindle microtubule assembly and accurate
      chromosome segregation remains obscure. Here, we report that GSK3beta interacts
      with the spindle-associated protein Astrin both in vitro and in vivo.
      Additionally, Astrin acts as a substrate for GSK3beta and is phosphorylated at
      Thr-111, Thr-937 ((S/T)P motif) and Ser-974/Thr-978 ((S/T)XXX(S/T)-p motif; p is
      a phosphorylatable residue). Inhibition of GSK3beta impairs spindle and
      kinetochore accumulation of Astrin and spindle formation at mitosis, suggesting
      that Astrin association with the spindle microtubule and kinetochore may be
      dependent on phosphorylation by GSK3beta. Conversely, depletion of Astrin by
      small interfering RNA has no detectable influence on the localization of
      GSK3beta. Interestingly, in vitro assays demonstrated that Astrin enhances
      GSK3beta-mediated phosphorylation of other substrates. Moreover, we showed that
      coexpression of Astrin and GSK3beta differentially increases GSK3beta-mediated
      Tau phosphorylation on an unprimed site. Collectively, these data indicate that
      GSK3beta interacts with and phosphorylates the spindle-associated protein Astrin,
      resulting in targeting Astrin to the spindle microtubules and kinetochores. In
      turn, the GSK3beta-Astrin complex may also facilitate further physiological and
      pathological phosphorylation.

PMID- 18055458
TI  - CREB modulates the functional output of nucleus accumbens neurons: a critical
      role of N-methyl-D-aspartate glutamate receptor (NMDAR) receptors.
AB  - Nucleus accumbens (NAc) medium spiny neurons cycle between two states, a
      functionally inactive downstate and a functionally active upstate. Here, we show
      that activation of the transcription factor cAMP-response element-binding protein
      (CREB), a common molecular response to several drugs of abuse, increases both
      duration of the upstate and action potential firing during the upstate. This
      effect of CREB is mediated by enhanced N-methyl-d-aspartate glutamate receptor
      (NMDAR) function: increased CREB activity increases both NMDAR-mediated synaptic
      currents and surface level of NMDARs, while inhibition of NMDARs abolishes the
      effect of CREB on upstate duration. Furthermore, mimicking the effect of CREB by
      pharmacological enhancement of NMDAR function in the NAc in vivo suppressed
      novelty- and cocaine-elicited locomotor activity. These findings suggest that by
      enhancing NMDAR-mediated synaptic transmission, CREB activation promotes the
      proportion of time NAc neurons spend in the upstate. This effect, along with the
      CREB enhancement of NAc membrane excitability (Dong, Y., Green, T., Saal, D.,
      Marie, H., Neve, R., Nestler, E. J., and Malenka, R. C. (2006) Nat. Neurosci. 9,
      475-477), may counteract drug-induced maladaptations in the NAc and thus
      ameliorate the addictive state.

PMID- 18055459
TI  - Common alterations in PBP1a from resistant Streptococcus pneumoniae decrease its
      reactivity toward beta-lactams: structural insights.
AB  - The development of high level beta-lactam resistance in the pneumococcus requires
      the expression of an altered form of PBP1a, in addition to modified forms of
      PBP2b and PBP2x, which are necessary for the appearance of low levels of
      resistance. Here, we present the crystal structure of a soluble form of PBP1a
      from the highly resistant Streptococcus pneumoniae strain 5204 (minimal
      inhibitory concentration of cefotaxime is 12 mg.liter(-1)). Mutations T371A,
      which is adjacent to the catalytic nucleophile Ser370, and TSQF(574-577)NTGY,
      which lie in a loop bordering the active site cleft, were investigated by site
      directed mutagenesis. The consequences of these substitutions on reaction
      kinetics with beta-lactams were probed in vitro, and their effect on resistance
      was measured in vivo. The results are interpreted in the framework of the crystal
      structure, which displays a narrower, discontinuous active site cavity, compared
      with that of PBP1a from the beta-lactam susceptible strain R6, as well as a
      reorientation of the catalytic Ser370.

PMID- 18055460
TI  - Intracellular interaction of interleukin-15 with its receptor alpha during
      production leads to mutual stabilization and increased bioactivity.
AB  - We show that co-expression of interleukin 15 (IL-15) and IL-15 receptor alpha (IL
      15Ralpha) in the same cell allows for the intracellular interaction of the two
      proteins early after translation, resulting in increased stability and secretion
      of both molecules as a complex. In the absence of co-expressed IL-15Ralpha, a
      large portion of the produced IL-15 is rapidly degraded immediately after
      synthesis. Co-injection into mice of IL-15 and IL-15Ralpha expression plasmids
      led to significantly increased levels of the cytokine in serum as well as
      increased biological activity of IL-15. Examination of natural killer cells and T
      lymphocytes in mouse organs showed a great expansion of both cell types in the
      lung, liver, and spleen. The presence of IL-15Ralpha also increased the number of
      CD44(high) memory cells with effector phenotype (CD44(high)CD62L-). Thus, mutual
      stabilization of IL-15 and IL-15Ralpha leads to remarkable increases in
      production, stability, and tissue availability of bioactive IL-15 in vivo. The in
      vivo data show that the most potent form of IL-15 is as part of a complex with
      its receptor alpha either on the surface of the producing cells or as a soluble
      extracellular complex. These results explain the reason for coordinate expression
      of IL-15 and IL-15Ralpha in the same cell and suggest that the IL-15Ralpha is
      part of the active IL-15 cytokine rather than part of the receptor.

PMID- 18055461
TI  - Role of NHERF1, cystic fibrosis transmembrane conductance regulator, and cAMP in
      the regulation of aquaporin 9.
AB  - Water and solute transport across the plasma membrane of cells is a crucial
      biological function that is mediated mainly by aquaporins and aquaglyceroporins.
      The regulation of these membrane proteins is still incompletely understood. Using
      the male reproductive tract as a model system in which water and glycerol
      transport are critical for the establishment of fertility, we now report a novel
      pathway for the regulation of aquaporin 9 (AQP9) permeability. AQP9 is the major
      aquaglyceroporin of the epididymis, liver, and peripheral leukocytes, and its
      COOH-terminal portion contains a putative PDZ binding motif (SVIM). Here we show
      that NHERF1, cystic fibrosis transmembrane conductance regulator (CFTR), and AQP9
      co-localize in the apical membrane of principal cells of the epididymis and the
      vas deferens, and that both NHERF1 and CFTR co-immunoprecipitate with AQP9.
      Overlay assays revealed that AQP9 binds to both the PDZ1 and PDZ2 domains of
      NHERF1, with an apparently higher affinity for PDZ1 versus PDZ2. Pull-down assays
      showed that the AQP9 COOH-terminal SVIM motif is essential for interaction with
      NHERF1. Functional assays on isolated tubules perfused in vitro showed a high
      permeability of the apical membrane to glycerol, which is inhibited by the AQP9
      inhibitor, phloretin, and is markedly activated by cAMP. The CFTR inhibitors DPC,
      GlyH-101 and CFTRinh-172 all significantly reduced the cAMP-activated glycerol
      induced cell swelling. We propose that CFTR is an important regulator of AQP9 and
      that the interaction between AQP9, NHERF1, and CFTR may facilitate the activation
      of AQP9 by cAMP.

PMID- 18055462
TI  - Stoichiometry of the peripheral stalk subunits E and G of yeast V1-ATPase
      determined by mass spectrometry.
AB  - The stoichiometry of yeast V(1)-ATPase peripheral stalk subunits E and G was
      determined by two independent approaches using mass spectrometry (MS). First, the
      subunit ratio was inferred from measuring the molecular mass of the intact V(1)
      ATPase complex and each of the individual protein components, using native
      electrospray ionization-MS. The major observed intact complex had a mass of
      593,600 Da, with minor components displaying masses of 553,550 and 428,300 Da,
      respectively. Second, defined amounts of V(1)-ATPase purified from yeast grown on
      (14)N-containing medium were titrated with defined amounts of (15)N-labeled E and
      G subunits as internal standards. Following protease digestion of subunit bands,
      (14)N- and (15)N-containing peptide pairs were used for quantification of subunit
      stoichiometry using matrix-assisted laser desorption/ionization-time of flight
      MS. Results from both approaches are in excellent agreement and reveal that the
      subunit composition of yeast V(1)-ATPase is A(3)B(3)DE(3)FG(3)H.

PMID- 18055463
TI  - Stress-induced translation of ATF5 mRNA is regulated by the 5'-untranslated
      region.
AB  - Activating transcription factor (ATF) 5 is a transcription factor belonging to
      the ATF/cAMP-response element-binding protein gene family. We previously reported
      that ATF5 mRNA expression increased in response to amino acid limitation. The
      ATF5 gene allows transcription of mRNAs with at least two alternative 5'
      untranslated regions (5'-UTRs), 5'-UTRalpha and 5'-UTRbeta, derived from
      exon1alpha and exon1beta. 5'-UTRalpha contains highly conserved sequences, in
      which the upstream open reading frames (uORFs) uORF1 and uORF2 are found in many
      species. This study was designed to investigate the potential role of 5'-UTRs in
      translational control. These 5'-UTRs differentially determined translation
      efficiency from mRNA. The presence of 5'-UTRalpha or 5'-UTRbeta represses
      translation from the downstream ATF5 ORF. Moreover, 5'-UTRalpha-regulated
      translational repression is released by amino acid limitation or NaAsO(2)
      exposure. This release was not seen for 5'-UTRbeta. Mutation of uAUG2 in the
      uORF2 of 5'-UTRalpha restored the basal expression and abolished the positive
      regulation by amino acid limitation or arsenite exposure. We demonstrated that
      phosphorylation of eukaryotic initiation factor 2alpha was required for amino
      acid limitation-induced translational regulation of ATF5. Furthermore, arsenite
      exposure activated the exogenously expressed heme-regulated inhibitor kinase and
      induced the phosphorylation of eukaryotic initiation factor 2alpha in
      nonerythroid cells. These results suggest that translation of ATF5 is regulated
      by the alternative 5'-UTR region of its mRNA, and ATF5 may play a role in
      protecting cells from amino acid limitation or arsenite-induced oxidative stress.

PMID- 18055464
TI  - The SH3-like domain switches its interaction partners to modulate the repression
      activity of mycobacterial iron-dependent transcription regulator in response to
      metal ion fluctuations.
AB  - Iron-dependent regulator (IdeR), a metal ion-activated pleiotropic transcription
      factor, plays a critical role in maintaining the intracellular iron homeostasis
      in Mycobacteria, which is important for the normal growth of the cells. This
      study was initially performed in an attempt to elucidate all potential
      interactions between the various domains of IdeR that occur in living
      mycobacterial cells. This led to a hitherto unidentified self-association for the
      SH3-like domain of IdeR. Further studies demonstrate that the SH3-like domain
      interacts with different partners in the dimeric forms of IdeR depending on the
      levels of metal ions in the environment: it undergoes inter-subunit self
      association in the metal-free DNA-non-binding form, but interacts with the N
      terminal domain in the metal-bound DNA-binding form in an intra-subunit manner to
      finely modulate the transcription repression activity of IdeR. Our more detailed
      mapping studies reveal that the SH3-like domain uses an overlapping surface to
      participate in these two interactions, which therefore occur in a mutually
      exclusive fashion. This novel mechanism would allow an effective and cooperative
      interconversion between the two functional forms of IdeR. Our data also
      demonstrate that a disturbance of the interactions involving the SH3-like domain
      impairs the transcription repression activity of IdeR and delays the growth of
      mycobacterial cells.

PMID- 18055465
TI  - c-Met inhibitors with novel binding mode show activity against several hereditary
      papillary renal cell carcinoma-related mutations.
AB  - c-Met is a receptor tyrosine kinase often deregulated in human cancers, thus
      making it an attractive drug target. One mechanism by which c-Met deregulation
      leads to cancer is through gain-of-function mutations. Therefore, small molecules
      capable of targeting these mutations could offer therapeutic benefits for
      affected patients. SU11274 was recently described and reported to inhibit the
      activity of the wild-type and some mutant forms of c-Met, whereas other mutants
      are resistant to inhibition. We identified a novel series of c-Met small molecule
      inhibitors that are active against multiple mutants previously identified in
      hereditary papillary renal cell carcinoma patients. AM7 is active against wild
      type c-Met as well as several mutants, inhibits c-Met-mediated signaling in MKN
      45 and U-87 MG cells, and inhibits tumor growth in these two models grown as
      xenografts. The crystal structures of AM7 and SU11274 bound to unphosphorylated c
      Met have been determined. The AM7 structure reveals a novel binding mode compared
      with other published c-Met inhibitors and SU11274. The molecule binds the kinase
      linker and then extends into a new hydrophobic binding site. This binding site is
      created by a significant movement of the C-helix and so represents an inactive
      conformation of the c-Met kinase. Thus, our results demonstrate that it is
      possible to identify and design inhibitors that will likely be active against
      mutants found in different cancers.

PMID- 18055466
TI  - Glucose directly links to lipid metabolism through high affinity interaction with
      peroxisome proliferator-activated receptor alpha.
AB  - The pathophysiology of diabetes is characterized not only by elevated glucose but
      also elevated long chain fatty acid levels. We show for the first time that the
      peroxisome proliferator-activated receptor-alpha (PPARalpha) binds glucose and
      glucose metabolites with high affinity, resulting in significantly altered
      PPARalpha secondary structure. Glucose decreased PPARalpha interaction with fatty
      acid metabolites and steroid receptor coactivator-1 while increasing PPARalpha
      interaction with DNA. Concomitantly, glucose increased PPARalpha interaction with
      steroid receptor coactivator-1, DNA binding, and transactivation of beta
      oxidation pathways in the presence of activating ligands. Heterodimerization of
      PPARalpha to the retinoid X receptor-alpha resulted in even larger increases in
      transactivation with the addition of glucose. These data suggest that PPARalpha
      is responsible for maintaining energy homeostasis through a concentration
      dependent regulation of both lipids and sugars and that hyperglycemic injury
      mediated by PPARalpha occurs not only indirectly through elevated long chain
      fatty acid levels but also through direct action of glucose on PPARalpha.

PMID- 18055467
TI  - Stoichiometry and localization of the stator subunits E and G in Thermus
      thermophilus H+-ATPase/synthase.
AB  - Proton-translocating ATPases are central to biological energy conversion.
      Although eukaryotes contain specialized F-ATPases for ATP synthesis and V-ATPases
      for proton pumping, eubacteria and archaea typically contain only one enzyme for
      both tasks. Although many eubacteria contain ATPases of the F-type, some
      eubacteria and all known archaea contain ATPases of the A-type. A-ATPases are
      closely related to V-ATPases but simpler in design. Although the nucleotide
      binding and transmembrane rotor subunits share sequence homology between A-, V-,
      and F-ATPases, the peripheral stalk is strikingly different in sequence,
      composition, and stoichiometry. We have analyzed the peripheral stalk of Thermus
      thermophilus A-ATPase by using phage display-derived single-domain antibody
      fragments in combination with electron microscopy and tandem mass spectrometry.
      Our data provide the first direct evidence for the existence of two peripheral
      stalks in the A-ATPase, each one composed of heterodimers of subunits E and G
      arranged symmetrically around the soluble A(1) domain. To our knowledge, this is
      the first description of phage display-derived antibody selection against a multi
      subunit membrane protein used for purification and single particle analysis by
      electron microscopy. It is also the first instance of the derivation of subunit
      stoichiometry by tandem mass spectrometry to an intact membrane protein complex.
      Both approaches could be applicable to the structural analysis of other membrane
      protein complexes.

PMID- 18055468
TI  - Dissemination and evaluation of the ASAS/EULAR recommendations for the management
      of ankylosing spondylitis: results of a study among 1507 rheumatologists.
AB  - BACKGROUND: Ten ASAS/EULAR recommendations for the management of ankylosing
      spondylitis (AS) were published in 2006. OBJECTIVES: (a) To disseminate and (b)
      to evaluate conceptual agreement with, and (c) application of, these
      recommendations as well as (d) potential barriers to the application. METHODS: A
      questionnaire was sent to rheumatologists in 10 countries. It included (a) the
      text of the recommendations; (b) rheumatologists' demographic variables; (c) two
      numerical rating scales from 1 to 10 for each recommendation: conceptual
      agreement with, and application of, the recommendation (10 indicates maximal
      agreement and maximal application); and (d) a list of potential barriers to the
      application of the recommendation. Statistical analysis included descriptive and
      multivariate analyses. RESULTS: 7206 questionnaires were sent out; 1507 (21%)
      were returned. Of the 1507 answering rheumatologists, 62% were men, mean (SD) age
      49 (9) years, and 34% had an academic position. Conceptual agreement with the
      recommendations was high (mean (SD) for all recommendations 8.9 (0.9)). Self
      reported application was also high (8.2 (1.0)). The difference between agreement
      and application varied across recommendations and countries. The most pronounced
      discrepancies were reported for use of anti-tumour necrosis factor drugs in a few
      countries, with funding as the most commonly reported barrier for application of
      this recommendation. CONCLUSION: This large project has helped the dissemination
      of the ASAS/EULAR recommendations for the management of AS and shows that
      conceptual agreement with the recommendations is very high. The project also
      highlights inequalities in access to healthcare for European citizens with AS.

PMID- 18055469
TI  - Long-term follow-up of relapsing/refractory anti-neutrophil cytoplasm antibody
      associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab
      (CAMPATH-1H).
AB  - OBJECTIVE: Lymphocytes are a contributor to the pathogenesis of anti-neutrophil
      cytoplasm antibody (ANCA) associated vasculitis (AASV). Conventional
      immunosuppressive therapy is associated with high rates of relapse and toxicity.
      Humanised monoclonal anti-CD52 antibodies (alemtuzumab, CAMPATH-1H) selectively
      deplete lymphocytes. We present long-term follow-up results of patients with
      relapsing/refractory AASV treated with CAMPATH-1H. PATIENTS AND METHODS: Between
      1991 and 1999, 71 patients with refractory or relapsing AASV received CAMPATH-1H
      at Addenbrooke's Hospital, Cambridge, UK. Other immunosuppressive drugs were
      discontinued and prednisolone was tapered to 10 mg/day. RESULTS: The mean follow
      up time was 5 years. In all, 79% had previously received cyclophosphamide (median
      dose 150 g). At the time of treatment, 42% had renal involvement (median
      creatinine for the cohort 101 micromol/litre excluding six patients who were
      dialysis dependent) and 18% were critically ill from AASV and required the
      intensive care unit. A total of 60 patients (85%) obtained a remission after
      treatment with CAMPATH-1H but 43 relapsed (median 9.2 months); 24 had a remission
      greater than 1 year, of which 10 had a remission of at least 3 years. A total of
      31 patients died (median survival time of 106 months). Age >50 years, dialysis
      dependency and the development of a severe infection at the time of treatment
      were associated with an increased risk of death in multivariable analysis.
      Adverse events were common; 28 patients developed an infection, 3 malignancy and
      8 thyroid disease. CONCLUSIONS: CAMPATH-1H induced remission in most patients
      with difficult to treat AASV. However, relapse and adverse events were common.
      Further study of CAMPATH-1H as an induction agent in AASV is warranted.

PMID- 18055470
TI  - The clinical response to infliximab in rheumatoid arthritis is in part dependent
      on pretreatment tumour necrosis factor alpha expression in the synovium.
AB  - OBJECTIVE: To determine whether the heterogeneous clinical response to tumour
      necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be
      predicted by TNFalpha expression in the synovium before initiation of treatment.
      METHODS: Prior to initiation of infliximab treatment, arthroscopic synovial
      tissue biopsies were obtained from 143 patients with active RA. At week 16,
      clinical response was evaluated using the 28-joint Disease Activity Score
      (DAS28). Immunohistochemistry was used to analyse the cell infiltrate as well as
      the expression of various cytokines, adhesion molecules and growth factors.
      Stained sections were evaluated by digital image analysis. Student t tests were
      used to compare responders (decrease in DAS28 > or =1.2) with non-responders
      (decrease in DAS28 <1.2) and multivariable regression was used to identify the
      independent predictors of clinical response. RESULTS: Synovial tissue analysis
      confirmed our hypothesis that the baseline level of TNFalpha expression is a
      significant predictor of response to TNFalpha blocking therapy. TNFalpha
      expression in the intimal lining layer and synovial sublining were significantly
      higher in responders than in non-responders (p = 0.047 and p = 0.008,
      respectively). The numbers of macrophages, macrophage subsets and T cells (all
      able to produce TNFalpha) were also significantly higher in responders than in
      non-responders. The expression of interleukin (IL)1beta, IL6, IL18, IL10, E
      selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion
      molecule (VCAM)-1, vascular endothelial growth factor (VEGF) and basic fibroblast
      growth factor (bFGF) was not associated with response to anti-TNFalpha treatment.
      CONCLUSION: The effects of TNFalpha blockade are in part dependent on synovial
      TNFalpha expression and infiltration by TNFalpha producing inflammatory cells.
      Clinical response cannot be predicted completely, indicating involvement of other
      as yet unknown mechanisms.

PMID- 18055471
TI  - Settings and artefacts relevant in colour/power Doppler ultrasound in
      rheumatology.
AB  - The paper explains the most important parameters for the use of colour and power
      Doppler in rheumatology. Recommendations for machine settings are given. The
      commonly encountered artefacts and their importance for image interpretation are
      explained.

PMID- 18055472
TI  - Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III,
      multi-centre, randomised, double-blind, placebo-controlled study in patients with
      rheumatoid arthritis and an inadequate response to methotrexate.
AB  - OBJECTIVES: This double-blind trial evaluated the efficacy and safety of
      abatacept or infliximab vs placebo. The primary objective of this study was to
      evaluate the mean change from baseline in Disease Activity Score (based on
      erythrocyte sedimentation rates; DAS28 (ESR)) for the abatacept vs placebo groups
      at day 197. METHODS: Patients with rheumatoid arthritis (RA) and an inadequate
      response to methotrexate (MTX) were randomised 3:3:2 to abatacept ( approximately
      10 mg/kg every 4 weeks, n = 156), infliximab (3 mg/kg every 8 weeks, n = 165), or
      placebo (every 4 weeks, n = 110) and background MTX. Safety and efficacy were
      assessed throughout the study. RESULTS: Similar patient demographics and clinical
      characteristics were present at baseline between groups, with mean scores of
      approximately 1.7 for HAQ-DI and 6.8 for DAS28 (ESR). At 6 months, mean changes
      in DAS28 (ESR) were significantly greater for abatacept vs placebo (-2.53 vs 
      1.48, p<0.001) and infliximab vs placebo (-2.25 vs -1.48, p<0.001). For abatacept
      vs infliximab treatment at day 365, reductions in the DAS28 (ESR) were -2.88 vs 
      2.25. At day 365, the following response rates were observed for abatacept and
      infliximab, respectively: American College of Rheumatology (ACR) 20, 72.4 and
      55.8%; ACR 50, 45.5 and 36.4%; ACR 70, 26.3 and 20.6%; low disease activity score
      (LDAS), 35.3 and 22.4%; DAS28-defined remission, 18.7 and 12.2%; good European
      League Against Rheumatism (EULAR) responses, 32.0 and 18.5%; and Health
      Assessment Questionnaire Disability Index (HAQ-DI), 57.7 and 52.7%. Mean changes
      in physical component summary (PCS) were 9.5 and 7.6, and mental component
      summary (MCS) were 6.0 and 4.0, for abatacept and infliximab, respectively. Over
      1 year, adverse events (AEs) (89.1 vs 93.3%), serious AEs (SAEs) (9.6 vs 18.2%),
      serious infections (1.9 vs 8.5%) and discontinuations due to AEs (3.2 vs 7.3%)
      and SAEs (2.6 vs 3.6%) were lower with abatacept than infliximab. CONCLUSIONS: In
      this study, abatacept and infliximab (3 mg/kg every 8 weeks) demonstrated similar
      efficacy. Overall, abatacept had a relatively more acceptable safety and
      tolerability profile, with fewer SAEs, serious infections, acute infusional
      events and discontinuations due to AEs than the infliximab group. TRIAL
      REGISTRATION NUMBER: NCT00095147.

PMID- 18055473
TI  - Allelic variation at the C-reactive protein gene associates to both hand
      osteoarthritis severity and serum high sensitive C-reactive protein levels in the
      GARP study.
AB  - OBJECTIVE: To gain more insight into the role of genetic variation of the C
      reactive protein (CRP) gene in serum CRP levels and osteoarthritis (OA). METHODS:
      Serum high sensitive CRP (S-HsCRP) levels were measured in the Genetics of
      osteoARthritis and Progression (GARP) study. Furthermore, to assess genetic
      variation of the CRP gene, genotypes of five tagging single nucleotide
      polymorphisms were assessed in the GARP study and a random control sample.
      RESULTS: A significant and consistent relation between S-HsCRP levels and
      observed haplotypes was identified. Additionally, a CRP haplotype, which also
      associated to a significantly higher expected phenotypic mean S-HsCRP level, was
      associated to severe hand OA. This haplotype was tagged by a single nucleotide
      polymorphism (rs3091244). Carriers of this allele have an increased risk for the
      presence of severe hand OA with an OR of 2.3 (95% confidence interval 1.2 to 4.3,
      p = 0.009). CONCLUSIONS: A haplotype of the CRP gene, associated to high basal S
      HsCRP level, is also associated to severity of hand OA, indicating that innate
      high basal S-HsCRP levels may influence OA onset.

PMID- 18055474
TI  - Utility of animal models for identification of potential therapeutics for
      rheumatoid arthritis.
AB  - Animal models of rheumatoid arthritis (RA) are widely used for testing potential
      new therapies for RA. However, the question of which animal model is most
      predictive of therapeutic efficacy in human RA commonly arises in data
      evaluation. A retrospective review of the animal models used to evaluate
      approved, pending RA therapies, and compounds that were discontinued during phase
      II or III clinical trials found that the three most commonly used models were
      adjuvant-induced arthritis (AIA) in rats and collagen-induced arthritis (CIA) in
      rats and mice. Limited data were found for more recently developed genetically
      modified animal models. Examination of the efficacy of various compounds in these
      animal models revealed that a compound's therapeutic efficacy, rather than
      prophylactic efficacy, in AIA and CIA models was more predictive of clinical
      efficacy in human RA than data from either model alone.

PMID- 18055475
TI  - A modified Delphi exercise to determine the extent of consensus with OMERACT
      outcome domains for studies of acute and chronic gout.
AB  - OBJECTIVES: To reach consensus with recommendations made by an OMERACT Special
      Interest Group (SIG). METHODS: Rheumatologists and industry representatives
      interested in gout rated and clarified, in three iterations, the importance of
      domains proposed by the OMERACT SIG for use in acute and chronic gout
      intervention studies. Consensus was defined as a value of less than 1 of the
      UCLA/RAND disagreement index. RESULTS: There were 33 respondents (61% response
      rate); all agreed the initial items were necessary, except "total body urate
      pool". Additional domains were suggested and clarification sought for defining
      "joint inflammation" and "musculoskeletal function". Items that demonstrated no
      clear decision were re-rated in the final iteration. There were six highly rated
      items (rating 1-2) with four slightly lower rating items (rating 3) for acute
      gout; and 11 highly rated items with eight slightly lower ratings for chronic
      gout. CONCLUSIONS: Consensus is that the following domains be considered
      mandatory for acute gout studies: pain, joint swelling, joint tenderness, patient
      global, physician global, functional disability; and for chronic gout studies:
      serum urate, gout flares, tophus regression, health-related quality of life,
      functional disability, pain, patient global, physician global, work disability
      and joint inflammation. Several additional domains were considered discretionary.

PMID- 18055476
TI  - Sustained response to long-term biologics and switching in psoriatic arthritis:
      results from real life experience.
AB  - OBJECTIVE: To investigate the response to biologic drugs in psoriatic arthritis
      and to quantify non-response and outcome from switching agents. METHODS: 60
      patients (33 men and 27 women, mean age 46 years, median disease duration 16
      years) prescribed biologic drugs for psoriatic arthritis between 2001 and 2006
      were studied. Response was evaluated using joint counts, C-reactive protein
      levels and disease activity scores (using 28 joints; DAS28). RESULTS: The mean
      percentage improvements seen were 56% in tender joint count, 70% in swollen joint
      count, 64% in C-reactive protein level and 36% in the overall disease activity
      score. Improvements were sustained beyond 24 months with no loss of effect. Side
      effects leading to cessation or switching of first-line therapy were only seen in
      5% of patients and non-response occurred in 20% long term. Overall, 90% of
      patients achieved a significant response, using switching in 20% of cases.
      Outcomes were similar regardless of drug used, duration of disease and subtype of
      arthritis. CONCLUSIONS: Treatment of active psoriatic arthritis with anti-tumour
      necrosis factor agents leads to a sustained response over 3 years with most
      patients tolerating these drugs well. The rate of non-response is low with the
      majority of patients responding to second- and third-line therapies.

PMID- 18055477
TI  - Long-term effects of bosentan on quality of life, survival, safety and
      tolerability in pulmonary arterial hypertension related to connective tissue
      diseases.
AB  - OBJECTIVES: This study investigated the long-term effects of bosentan, an oral
      endothelin ET(A)/ET(B) receptor antagonist, in patients with pulmonary arterial
      hypertension (PAH) exclusively related to connective tissue diseases (CTD).
      METHODS: A total of 53 patients with PAH related to connective tissue diseases
      (PAH-CTD) in World Health Organization (WHO) functional class III received
      bosentan 62.5 mg twice a day for 4 weeks and then 125 mg twice a day for 44 weeks
      in this open non-comparative study. Assessments at weeks 16 and 48 included WHO
      class, clinical worsening, quality of life (Short-Form Health Survey (SF-36) and
      health assessment questionnaire (HAQ) modified for scleroderma), and survival
      (week 48 only). Safety and tolerability were monitored throughout the study.
      RESULTS: At week 48, WHO class improved in 27% of patients (95% CI 16-42%) and
      worsened in 16% (95% CI 7-29%). Kaplan-Meier estimates were 68% (95% CI 55-82%)
      for absence of clinical worsening and 92% (95% CI 85-100%) for survival. Overall
      changes in quality of life were minimal. There were no unexpected side effects
      observed during the study. CONCLUSIONS: In most patients, bosentan was associated
      with improvement or stability of clinical status. The 92% estimate for survival
      at 48 weeks is a significant achievement in this patient population.

PMID- 18055479
TI  - Putative promoter regions of miRNA genes involved in evolutionarily conserved
      regulatory systems among vertebrates.
AB  - MOTIVATION: Just as transcription factors, miRNA genes modulate global patterns
      of gene expression during differentiation, metabolic activation, stimulus
      response and also carcinogenesis. However, little is currently known how the
      miRNA gene expression itself is regulated owing to lack of basic information of
      their gene structure. Global prediction of promoter regions of miRNA genes would
      allow us to explore the mechanisms underlying gene-regulatory mechanisms
      involving these miRNAs. RESULTS: We speculate that if specific miRNA molecules
      are involved in evolutionarily conserved regulatory systems in vertebrates, this
      would entail a high level of conservation of the promoter of miRNA gene as well
      as the miRNA molecule. By our current screening of putative promoter regions of
      miRNA genes (miPPRs) on this base, we identified 59 miPPRs that would direct
      production of 79 miRNAs. We present both biochemical and bioinformatical
      verifications of these putative promoters.

PMID- 18055478
TI  - Myeloid-related proteins S100A8/S100A9 regulate joint inflammation and cartilage
      destruction during antigen-induced arthritis.
AB  - OBJECTIVE: To study the active involvement of Myeloid-related proteins S100A8 and
      S100A9 in joint inflammation and cartilage destruction during antigen-induced
      arthritis (AIA). METHODS: Joint inflammation and cartilage destruction was
      measured with 99mTc uptake and histology. The role of S100A8/A9 was investigated
      by inducing AIA in S100A9-/- mice that also lack S100A8 at protein level, or
      after intra-articular injection of rS100A8 in mouse knee joints. Cartilage
      destruction was measured using immunolocalisation of the neoepitope VDIPEN or
      NITEGE. mRNA levels of matrix metalloproteinases (MMPs) and cytokines were
      measured using reverse transcriptase (RT)-PCR. RESULTS: Immunisation of S100A9-/-
      mice with the antigen mBSA induced normal cellular and humoral responses, not
      different from wild type (WT) controls. However, joint swelling measured at day 3
      and 7 after AIA induction was significantly lower (36 and 70%, respectively).
      Histologically, at day 7 AIA, cellular mass was much lower (63-80%) and
      proteoglycan depletion from cartilage layers was significantly reduced (between
      50-95%). Cartilage destruction mediated by MMPs was absent in S100A9-/- mice but
      clearly present in controls. MMP3, 9 and 13 mRNA levels were significantly
      lowered in arthritic synovia of S100A9-/-. In vitro stimulation of macrophages by
      the heterodimer S100A8/A9 or S100A8 elevated mRNA levels of MMP3, 9 and in
      particular MMP13. Intra-articular injection of S100A8 caused prominent joint
      inflammation and depletion of proteoglycans at day 1. Significant upregulation of
      mRNA levels of S100A8/A9, cytokines (interleukin 1 (IL1)), MMPs (MMP3, MMP13 and
      a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4) was
      found in the synovium and correlated with strong upregulation of NITEGE
      neoepitopes within the cartilage layers. CONCLUSIONS: S100A8/A9 regulate joint
      inflammation and cartilage destruction during antigen-induced arthritis.

PMID- 18055480
TI  - Inotropic support and peritoneal dialysis adequacy in neonates after cardiac
      surgery.
AB  - We describe the impact of cardiovascular pharmacologic support on peritoneal
      dialysis adequacy in 20 neonates who required postoperative renal replacement
      therapy following cardiopulmonary bypass exposure. Peritoneal dialysis was
      administered for 2.5 (2) days. Peritoneal dialysis creatinine clearance was 3.4
      (2.1) ml/min/1.73 m(2) and ultrafiltration rate was 9.75 (10) ml/h. Residual
      creatinine clearance was 31 (26) ml/min/1.73 m(2). Peritoneal dialysis creatinine
      clearance appeared to be a function of dialysate flow up to 100 ml/h. No
      correlation was present between inotropes and vasopressors infusion and
      peritoneal dialysis creatinine clearance/ultrafiltration rate. LDH clearance was
      0.59 (0.85) ml/min/1.73 m(2) and it did not appear to have a correlation with
      dialysate flow. Patients in-hospital mortality was 20%, significantly higher than
      overall neonatal population admitted to our ICU (4.8%, P=0.02). Peritoneal
      dialysis in neonates allows optimal ultrafiltration rate and adequate small
      solute clearance, irrespective of hemodynamic status or vasopressor support.

PMID- 18055481
TI  - Delayed recovery of human leukocyte antigen-DR expression after cardiac surgery
      with early non-lethal postoperative complications: only an epiphenomenon?
AB  - HLA-DR expression on peripheral blood monocytes is reduced after cardiac surgery.
      Little is known about the reconstitution of HLA-DR expression on peripheral blood
      monocytes in patients suffering from early non-fatal perioperative complications.
      We conducted a prospective study to prove whether these complications adversely
      affect the recovery of HLA-DR expression. Before surgery (d0), on the first (d1),
      third (d3), fifth (5th) postoperative days, blood samples were collected from 90
      patients who underwent elective cardiac surgery with cardiopulmonary bypass
      (CPB). HLA-DR expression was analysed flow cytometrically. Eleven patients
      experienced postoperative complications [mechanical ventilation of 24-48 h (n=6);
      reinstitution of CPB (n=2) intraoperatively; laparotomy (n=1), re-thoracotomy
      (n=1), re-intubation (n=1) within the first 24 h after surgery]. All patients
      showed a reduced HLA-DR expression after surgery with nadirs at d1 and d3.
      Whereas the values increased from d3 to d5 in patients with an uneventful
      clinical course, HLA-DR expression remained suppressed in patients with
      complications. HLA-DR expression is reduced after cardiac surgery with CPB. A
      delayed recovery of HLA-DR expression is seen in patients with early
      perioperative complications. These non-fatal complications appear to represent a
      'second hit' resulting in a prolonged deficiency of the innate immune system.
      This might predispose to further infectious and septic complications.

PMID- 18055482
TI  - Do beating heart techniques applied to combined valve and graft operations reduce
      myocardial damage?
AB  - We examined the outcomes of combined beating heart CABG and valve surgery
      (hybrid) and compared these to conventional CABG and valve surgery
      (conventional). Between April 1997 and March 2006, 388 patients received combined
      CABG and valve surgery. Patient characteristics and cardiac enzyme release were
      collected prospectively. To account for differences in case-mix we used logistic
      regression to develop a propensity score for hybrid group membership and then
      performed a propensity-matched analysis. One hundred and forty patients underwent
      hybrid operation with a mean logistic EuroSCORE of 13.5%, compared to 248 who
      underwent conventional operation with a mean logistic EuroSCORE of 10.9%
      (P=0.006). Eighty-two patients from each group were successfully matched. The
      mean logistic EuroSCORE after matching was similar between the groups (11.3% vs.
      12.9%; P=0.48). The median number of grafts per patient was also similar, three
      in each group (P=0.98). Post-op CK-MB levels were found to be significantly lower
      for hybrid patients (44 U/I vs. 29.5 U/I; P=0.037). In-hospital mortality was not
      statistically different (9.8% vs. 6.1%; P=0.39). Survival at 5 years was 74% for
      hybrid and 71% for conventional group (P=0.92). CK-MB levels in patients
      receiving hybrid CABG and valve surgery are reduced compared to conventional CABG
      and valve surgery.

PMID- 18055483
TI  - Do the benefits of shorter hospital stay associated with the use of fleece-bound
      sealing outweigh the cost of the materials?
AB  - OBJECTIVES: To compare the cost of materials and hospitalization for standard
      techniques (suturing, stapling and electrocautery) for sealing the lung after
      pulmonary resection with those for a fleece-bound sealing procedure. METHODS:
      This cost comparison analysis uses as its basis a prospective randomised clinical
      trial involving 152 patients with pulmonary lobectomy/segmentectomy (standard
      technique group: 77 patients; fleece-bound sealing group: 75 patients). The cost
      comparison was performed from the economic perspective of Austrian and German
      hospitals, taking into consideration the cost of materials for the two
      alternatives as well as the mean time to hospital discharge. RESULTS: The
      clinical study found significantly smaller postoperative air leaks in the fleece
      bound sealing group. The mean times to chest drain removal and to hospital
      discharge were also significantly reduced after application of fleece-bound
      sealing [5.1 vs. 6.3 days (P=0.022) and 6.2 vs. 7.7 days (P=0.01), respectively].
      The cost of materials for sealing air leaks amounted to euro47 per patient in the
      standard technique group and euro410 per patient in the fleece-bound sealing
      group. The 1.5-day reduction in the length of hospital stay associated with
      fleece-bound sealing represents a saving of euro462 per patient. CONCLUSIONS:
      There was an overall saving of euro99 for the fleece-bound sealing procedure
      compared to standard techniques for sealing the lung following pulmonary
      resection.

PMID- 18055484
TI  - Angiotensin-II acute regulation of rapid response genes in human, bovine, and rat
      adrenocortical cells.
AB  - Angiotensin-II (Ang-II) regulates adrenal steroid production and gene
      transcription through several signaling pathways. Changes in gene transcription
      occur within minutes after Ang-II stimulation, causing an increase in aldosterone
      production and subsequent increase in the overall capacity to produce
      aldosterone. Our goal was to compare the Ang-II regulation of early gene
      expression and confirm the up-regulation of selected genes using quantitative
      real-time RT-PCR (qPCR) across three species, such as, human, bovine, and rat.
      Microarray analyses were performed using samples from control and Ang-II (10 nM)
      treated (1 h) cells from human adrenocortical tumor cell line H295R, and primary
      adrenal glomerulosa cells from bovine and rat, applied respectively to human,
      bovine, and rat chips. qPCR was performed to confirm up-regulation of selected
      genes using mRNA. The microarray comparison revealed 18% similarity among the top
      50 up-regulated genes, with human/rat, 20%; human/bovine, 36%; and rat/bovine,
      26% similarity. The gene list generated by this comparison included: activating
      transcription factor 3, B-cell translocation gene (BTG2), Nuclear receptor
      subfamily 4, group A, member 1 (NR4A1), NR4A2, NR4A3, early growth response 1, v
      fos FBJ murine osteosarcoma viral oncogene homolog (c-FOS), FOSB, and Jun family
      member B (JUNB). Pretreatment of H295R cells with cycloheximide had no effect on
      Ang-II induction of these genes, suggesting that they are direct targets of Ang
      II signaling. The Ang-II gene targets have been defined in three different
      adrenocortical model systems. Several of the listed genes have previously been
      described as being key regulators of adrenocortical function. The presence of
      adrenal cell common genes in such distinct cell models strengthens the hypothesis
      that these genes are regulators of aldosterone production.

PMID- 18055485
TI  - Calcitonin targets extracellular signal-regulated kinase signaling pathway in
      human cancers.
AB  - The mitogen-activated protein kinases (MAPKs) signaling pathway is a potential
      target in cancer therapy. Constitutive phosphorylated extracellular signal
      regulated kinase (ERK1/2), which is one of the MAPKs has been detected in a
      variety of tumors. Calcitonin (CT) is a polypeptide hormone secreted by the
      thyroid gland and has been used to treat the osteoporosis and humoral
      hypercalcemia of malignancy. We report that CT decreases ERK1/2 phosphorylation
      in cancer cells showing constitutive phosphorylated ERK1/2. In MDA-MB-231 cells,
      a breast cancer cell line showing constitutive phosphorylated ERK1/2, CT
      phosphorylated c-Raf at Ser(259) via the protein kinase A pathway, resulting in
      suppression of ERK1/2 phosphorylation. CT significantly reduced the tumor volume
      of MDA-MB-231 cells showing constitutive phosphorylated ERK1/2 compared with
      saline buffer. However, CT did not exert any significant effects on the
      proliferation of MCF-7 cells, a breast cancer cell line, showing non-constitutive
      phosphorylated ERK1/2. These novel findings indicate that CT may be used to
      target ERK in the treatment of cancer.

PMID- 18055486
TI  - Prasugrel achieves greater and faster P2Y12receptor-mediated platelet inhibition
      than clopidogrel due to more efficient generation of its active metabolite in
      aspirin-treated patients with coronary artery disease.
AB  - AIMS: P2Y(12) receptor antagonism and platelet inhibition by prasugrel vs.
      clopidogrel were investigated in patients with stable coronary artery disease.
      METHODS AND RESULTS: One hundred and ten aspirin treated subjects were randomized
      to double-blind treatment with clopidogrel (n = 55) 600 mg loading dose (LD) and
      75 mg maintenance dose (MD) or prasugrel (n = 55) 60 mg LD and 10 mg MD for 28
      days. Concentrations of prasugrel and clopidogrel active metabolites were
      determined. Platelet aggregation to 20 microM adenosine diphosphate, measured by
      light transmission aggregometry, was reported as maximal platelet aggregation
      (MPA). P2Y(12) function was assessed by the vasodilator-stimulated phosphoprotein
      assay and reported as platelet reactivity index (PRI). The same pharmacodynamic
      measurements were performed after ex vivo addition of clopidogrel's active
      metabolite. At 2 h post-LD, mean MPA was 31 vs. 55%, and mean PRI 8.3 vs. 55.9%
      for prasugrel and clopidogrel, respectively (P < 0.001). During MD on day 14 and
      28, mean MPA was 42 vs. 54% and mean PRI was 25 vs. 51%, respectively (P <
      0.001). Peak level of the active metabolite and P2Y(12) inhibition occurred
      earlier and was greater with prasugrel (P < 0.001). Mean area under the time
      concentration curve (AUC; microM.h) of the respective active metabolite was
      higher with prasugrel vs. clopidogrel post-LD (1.11 vs. 0.24) and post-MD (0.16
      vs. 0.062). Ex vivo addition of clopidogrel's active metabolite further reduced
      PRI in all patients whose platelets were not already maximally inhibited.
      CONCLUSION: In aspirin-treated subjects with coronary artery disease, prasugrel
      60/10 mg provides faster onset and greater inhibition of P2Y(12) receptor
      mediated platelet aggregation than clopidogrel 600/75 mg, because of greater and
      more efficient generation of the active metabolite.

PMID- 18055487
TI  - New point of care Chlamydia Rapid Test--bridging the gap between diagnosis and
      treatment: performance evaluation study.
AB  - OBJECTIVE: To evaluate the performance of a new Chlamydia Rapid Test with vaginal
      swab specimens as a potential tool for chlamydia diagnosis and screening. DESIGN:
      Performance evaluation study. Settings A young people's sexual health centre
      (site 1) and two genitourinary medicine clinics (sites 2 and 3) in the United
      Kingdom. PARTICIPANTS: 1349 women aged between 16 and 54 attending one of the
      three clinics. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive
      predictive value, and negative predictive value of the Chlamydia Rapid Test
      versus polymerase chain reaction and strand displacement amplification assays;
      correlation between the Chlamydia Rapid Test visual signal and organism load;
      acceptability to participants of self collected vaginal swabs as the specimen
      type for Chlamydia testing. RESULTS: Polymerase chain reaction positivity rates
      for Chlamydia trachomatis infection were 8.4% (56/663) at site 1, 9.4% (36/385)
      at site 2, and 6.0% (18/301) at site 3. Compared with polymerase chain reaction
      assay, the resolved sensitivity, specificity, positive predictive value, and
      negative predictive value of the Chlamydia Rapid Test were 83.5% (91/109), 98.9%
      (1224/1238), 86.7% (91/105), and 98.6% (1224/1242). Compared with strand
      displacement amplification assay, sensitivity and specificity of the Chlamydia
      Rapid Test were 81.6% (40/49) and 98.3% (578/588). Organism load of self
      collected vaginal swabs ranged from 5.97x10(2) to 1.09x10(9) Chlamydia plasmids
      per swab, which correlated well with the Chlamydia Rapid Test's visual signal
      (r=0.6435, P<0.0001). Most (95.9%) surveyed participants felt comfortable about
      collecting their own swabs. CONCLUSIONS: The performance of the Chlamydia Rapid
      Test with self collected vaginal swabs indicates that it would be an effective
      same day diagnostic and screening tool for Chlamydia infection in women. The
      availability of Chlamydia Rapid Test results within 30 minutes allows for
      immediate treatment and contact tracing, potentially reducing the risks of
      persistent infection and onward transmission. It could also provide a simple and
      reliable alternative to nucleic acid amplification tests in chlamydia screening
      programmes.

PMID- 18055488
TI  - False-positive Aspergillus galactomannan antigenaemia after haematopoietic stem
      cell transplantation.
AB  - OBJECTIVES: Although Aspergillus galactomannan (GM) antigen detection is widely
      applied in the diagnosis of invasive aspergillosis (IA), false-positive reactions
      with fungus-derived antibiotics, other fungal genera or the passage of dietary GM
      through injured mucosa are a matter of concern. The aim of this study was to
      investigate the cumulative incidence and risk factors for false-positive GM
      antigenaemia. PATIENTS AND METHODS: The records of 157 adult allogeneic
      haematopoietic stem cell transplantation (HSCT) recipients were retrospectively
      analysed. Episodes of positive GM antigenaemia, defined as two consecutive GM
      results with an optical density index above 0.6, were classified into true, false
      and inconclusive GM antigenaemia by reviewing the clinical course. RESULTS:
      Twenty-five patients developed proven or probable IA with a 1 year cumulative
      incidence of 12.9%, whereas 50 experienced positive GM antigenaemia with an
      incidence of 32.2%. Among the total 58 positive episodes of the 50 patients, 29
      were considered false-positive. The positive predictive value (PPV) was lower
      during the first 100 days than beyond 100 days after HSCT (37.5% versus 58.8%).
      Gastrointestinal chronic graft-versus-host disease (GVHD) was identified as the
      only independent significant factor for the increased incidence of false-positive
      GM antigenaemia (PPV 0% versus 66.7%, P = 0.02). CONCLUSIONS: GM antigen results
      must be considered cautiously in conjunction with other diagnostic procedures
      including computed tomography scans, especially during the first 100 days after
      HSCT and in patients with gastrointestinal chronic GVHD.

PMID- 18055489
TI  - Prophylaxis of ophthalmia neonatorum comparison of betadine, erythromycin and no
      prophylaxis.
AB  - Ophthalmia neonatorum is a form of bacterial conjunctivitis contracted by
      newborns during delivery and occurs during the first month of life. Etiologic
      factors include Neisseria gonorrhoeae, Chlamydia trachomatis, viruses and
      chemicals. Its prevalence differs in different parts of the world and is
      dependent mainly upon socioeconomic conditions, level of knowledge about general
      health, standard of maternal healthcare as well as the type of prophylactic
      program used. This randomized clinical trial was performed during the years 2004
      05 in the Delivery Section of Vali-e-Asr Hospital on 330 neonates who were
      divided into three equal groups of 110; Group A received betadine eye drops,
      Group B received Erythromycin eye drops and Group C (control group) received no
      treatment. Results showed that clinical conjunctivitis occurred in 52 subjects
      (17%), 58% of whom constituted males. On the whole, 9% of the infected newborns
      were from group A, 18.4% from group B and 22.4% from group C. It was concluded
      that 2.5% sterile betadine eye drops had a pronounced effect on ophthalmia
      neonatorum (p = 0.030).

PMID- 18055491
TI  - Cerebral vasoconstriction, headache and sometimes stroke: one syndrome or many?

PMID- 18055492
TI  - Quantitative diffusion MRI of hippocampus as a surrogate marker for post
      traumatic epileptogenesis.
AB  - The need to use animal models to develop imaging markers that could be linked to
      electrophysiological abnormalities in epilepsy and able to predict
      epileptogenicity in human studies is widely acknowledged. This study aimed to
      investigate the value of early magnetic resonance imaging (MRI) in predicting the
      long-term increased seizure susceptibility in the clinically relevant model of
      post-traumatic epilepsy (PTE). Moderate traumatic brain injury (TBI) was induced
      by lateral fluid-percussion in two groups of adult rats (34 injured, 16
      controls). In Experiment 1, MRI follow-up was performed using a 4.7 T magnet at 3
      h, 3 days, 9 days, 23 days, 2 months, 3 months and 6 months after TBI. T2 and 1/3
      of the trace of the diffusion tensor (D(av)) were quantified from a single slice
      using a fast spin-echo sequence. In Experiment 2, MRI was performed at 7 and 11
      months post-injury. In both groups, seizure susceptibility was tested by
      injecting a single dose of pentylenetetrazol at 12 months post-injury.
      Electrographic and behavioural responses were monitored for 1 h. Total number of
      spikes, total number of epileptiform discharges (EDs) and latency to first spike
      were measured. Finally, the severity of mossy fibre sprouting was evaluated. In
      both experiments, EEG parameters such as total number of spikes or EDs proved to
      be reliable indicators of increased seizure susceptibility in injured animals
      when compared to controls (P < 0.05). In the hippocampus ipsilateral to TBI,
      D(av) correlated with these EEG parameters at both early (3 h), and chronic (23
      days, 2, 3, 6, 7 and 11 months) time points after TBI, as well as with the
      density of mossy fibre sprouting. These results for the first time demonstrate
      that quantitative diffusion MRI can serve as a tool to facilitate prediction of
      increased seizure susceptibility in a clinically relevant model of human PTE.

PMID- 18055493
TI  - Analysis of the UK diagnostic strategy for limb girdle muscular dystrophy 2A.
AB  - Diagnosis of limb girdle muscular dystrophy type 2A can be complex due to
      phenotypic variability, lack of precision of protein analysis in muscle biopsies,
      and absence of mutational hot spots in the CAPN3 gene. The aim of this study was
      to review clinical and biopsy data from a group of patients with known CAPN3
      genetic status to validate and refine our current diagnostic strategy, which
      combines clinical information and protein analysis to direct gene testing. We
      analysed 85 patients in whom CAPN3 gene sequencing had been performed. Forty-two
      patients had two mutations, 15 a single mutation and in 28 no mutation was found.
      We identified clinical features that clearly discriminated the LGMD2A patients.
      These were: presence of scapular winging, contractures and normal respiratory
      function. In addition, a typical pattern of muscle weakness on manual muscle
      testing could be confirmed. Interpretation of protein expression obtained by
      Western blot was complex and involved the analysis of a number of bands detected
      by two antibodies for calpain 3. Loss of all calpain 3 bands was 100% specific
      for LGMD2A, but this pattern was found in only 23%. Absence or reduction of the
      approximately 60 kDa bands was also highly specific for LGMD2A, while increased
      abundance was highly predictive of no mutations being found even where other
      bands were reduced, suggesting that this is the most sensitive marker of
      artefactual protein degradation. Twenty-three percent of the patients with two
      mutations had normal full-sized calpain 3 protein, consistent with the finding of
      mutations localized in parts of the gene likely or proven to be involved in
      autolytic activity. Clinical and biochemical findings in patients with only one
      mutation were similar to patients with two mutations, indicating that other gene
      analysis techniques should be used before excluding the diagnosis. Our analysis
      confirms that our strategy is still valid to prioritize genetic testing in this
      complex group of patients, provided patients with normal protein but a suggestive
      clinical phenotype are not excluded from genetic testing.

PMID- 18055494
TI  - Clinical and morphological phenotype of the filamin myopathy: a study of 31
      German patients.
AB  - Mutations in the filamin C gene (FLNC) cause a myofibrillar myopathy (MFM),
      morphologically characterized by focal myofibrillar destruction and abnormal
      accumulation of several proteins within skeletal muscle fibres. We studied 31
      patients from four German families to evaluate the phenotype of filaminopathy.
      All patients harboured the same p.W2710X mutation in FLNC. Haplotype analysis
      suggested a founder mutation in these German filaminopathy families. The mean age
      at onset of clinical symptoms was 44 +/- 6 years (range, 24-57 years). Slowly
      progressive muscle weakness was mostly pronounced proximally, initially affecting
      the lower extremities and involving the upper extremities in the course of
      disease progression, similar to the distribution of weakness seen in limb-girdle
      muscular dystrophies (LGMD). Patients frequently developed respiratory muscle
      weakness. About one-third of the patients showed cardiac abnormalities comprising
      conduction blocks, tachycardia, diastolic dysfunction and left ventricular
      hypertrophy indicating a cardiac involvement in filaminopathy. Serum creatine
      kinase levels varied from normal up to 10-fold of the upper limit. Magnetic
      resonance imaging studies showed a rather homogenous pattern of muscle
      involvement in the lower extremities differing from that in other types of MFM.
      Myopathological features included perturbation of myofibrillar alignment,
      accumulation of granulofilamentous material similar to that seen in primary
      desminopathies and abnormal intracellular protein deposits typical of MFM.
      Decreased activities of oxidative enzymes and fibre hypertrophy seem to be early
      features, whereas dystrophic changes were present in advanced stages of
      filaminopathy. Rimmed vacuoles were detected in only a few cases. The
      intracellular aggregates were composed of a variety of proteins including filamin
      C, desmin, myotilin, Xin, dystrophin and sarcoglycans. Therapy is so far limited
      to symptomatic treatment. The German filaminopathy cohort, the largest group of
      patients studied so far, shares phenotypic features with LGMD and presents with
      characteristic histopathological findings of MFM.

PMID- 18055495
TI  - McLeod myopathy revisited: more neurogenic and less benign.
AB  - The X-linked McLeod neuroacanthocytosis syndrome (MLS) has originally been
      denoted as 'benign' McLeod myopathy. We assessed the clinical findings and the
      muscle pathology in the eponymous index patient, Hugh McLeod, and in nine
      additional MLS patients. Only one patient had manifested with neuromuscular
      symptoms. During a mean follow-up of 15 years, however, eight patients including
      the initial index patient showed elevated skeletal muscle creatine kinase levels
      ranging from 300 to 3000 U/L, and had developed muscle weakness and atrophy. Two
      patients had disabling leg weakness. Muscle histology was abnormal in all 10
      patients. Clear but unspecific myopathic changes were found in only four
      patients. All patients, however, had neurogenic changes of variable degree. Post
      mortem motor and sensory nerve examinations support the view that muscle atrophy
      and weakness are predominantly due to an axonal motor neuropathy rather than to a
      primary myopathy. Multisystem manifestations developed in eight patients at a
      mean age of 39 years. Three patients manifested with psychiatric features
      comprising schizophrenia-like psychosis and personality disorder, two presented
      with generalized seizures and one with chorea. During follow-up, seven patients
      developed chorea, six had psychiatric disorders, five had cognitive decline and
      three had generalized seizures. Five patients died because of MLS-related
      complications including sudden cardiac death, chronic heart failure and pneumonia
      between 55 and 69 years. In conclusion, our findings confirm that MLS is not a
      benign condition but rather a progressive multisystem disorder sharing many
      features with Huntington's disease.

PMID- 18055496
TI  - Mature astrocytes in the adult human neocortex express the early neuronal marker
      doublecortin.
AB  - Doublecortin (DCX) is a microtubule-associated protein expressed by migrating
      neuroblasts and is considered to be a reliable marker of neurogenesis. DCX has
      been used to study the relation between neurogenesis in adult human brain and
      neurological and neurodegenerative disease processes in the search for putative
      therapeutic strategies. Using autopsy and surgically resected tissue from a total
      of 60 patients, we present evidence that DCX is present in several cellular
      compartments of differentiated astrocytes in the adult human neocortex. One of
      these compartments consisted of peripheral processes forming punctate envelopes
      around mature neuronal cell bodies. Markers of glial activation, such as GFAP and
      HLA, were not associated with DCX immunoreactivity, however, the presence of
      cytoarchitectural alterations tended to correlate with reduced DCX staining of
      astrocytic somata. Interestingly, local Alzheimer pathology that showed no
      relation with cytoarchitectural abnormalities appeared to correlate negatively
      with the expression of DCX in the astrocytic somata. In combination with the
      literature our data support the view that DCX in the adult human neocortex may
      have a function in glia-to-neuron communication. Furthermore, our results
      indicate that in the adult human neocortex DCX is neither a reliable nor a
      selective marker of neurogenesis.

PMID- 18055497
TI  - Binding MOAD, a high-quality protein-ligand database.
AB  - Binding MOAD (Mother of All Databases) is a database of 9836 protein-ligand
      crystal structures. All biologically relevant ligands are annotated, and
      experimental binding-affinity data is reported when available. Binding MOAD has
      almost doubled in size since it was originally introduced in 2004, demonstrating
      steady growth with each annual update. Several technologies, such as natural
      language processing, help drive this constant expansion. Along with increasing
      data, Binding MOAD has improved usability. The website now showcases a faster,
      more featured viewer to examine the protein-ligand structures. Ligands have
      additional chemical data, allowing for cheminformatics mining. Lastly, logins are
      no longer necessary, and Binding MOAD is freely available to all at
      http://www.BindingMOAD.org.

PMID- 18055499
TI  - Alternative splicing and protein structure evolution.
AB  - Alternative splicing is thought to be one of the major sources for functional
      diversity in higher eukaryotes. Interestingly, when mapping splicing events onto
      protein structures, about half of the events affect structured and even highly
      conserved regions i.e. are non-trivial on the structure level. This has led to
      the controversial hypothesis that such splice variants result in nonsense
      mediated mRNA decay or non-functional, unstructured proteins, which do not
      contribute to the functional diversity of an organism. Here we show in a
      comprehensive study on alternative splicing that proteins appear to be much more
      tolerant to structural deletions, insertions and replacements than previously
      thought. We find literature evidence that such non-trivial splicing isoforms
      exhibit different functional properties compared to their native counterparts and
      allow for interesting regulatory patterns on the protein network level. We
      provide examples that splicing events may represent transitions between different
      folds in the protein sequence-structure space and explain these links by a common
      genetic mechanism. Taken together, those findings hint to a more prominent role
      of splicing in protein structure evolution and to a different view of phenotypic
      plasticity of protein structures.

PMID- 18055498
TI  - DNA replication stress, genome instability and aging.
AB  - Genome instability is a fundamentally important component of aging in all
      eukaryotes. How age-related genome instability occurs remains unclear. The free
      radical theory of aging posits oxidative damage to DNA and other cellular
      constituents as a primary determinant of aging. More recent versions of this
      theory predict that mitochondria are a major source of reactive oxygen species
      (ROS) that cause oxidative damage. Although substantial support for the free
      radical theory exists, the results of some tests of this theory have been
      contradictory or inconclusive. Enhanced growth signaling also has been implicated
      in aging. Many efforts to understand the effects of growth signaling on aging
      have focused on inhibition of oxidative stress responses that impact oxidative
      damage. However, recent experiments in the model organism Saccharomyces
      cerevisiae (budding yeast) and in higher eukaryotes suggest that growth signaling
      also impacts aging and/or age-related diseases--including cancer and
      neurodegeneration--by inducing DNA replication stress, which causes DNA damage.
      Replication stress, which has not been broadly considered as a factor in aging,
      may be enhanced by ROS that signal growth. In this article, we review evidence
      that points to DNA replication stress and replication stress-induced genome
      instability as important factors in aging.

PMID- 18055500
TI  - InParanoid 6: eukaryotic ortholog clusters with inparalogs.
AB  - The InParanoid eukaryotic ortholog database (http://InParanoid.sbc.su.se/) has
      been updated to version 6 and is now based on 35 species. We collected all
      available 'complete' eukaryotic proteomes and Escherichia coli, and calculated
      ortholog groups for all 595 species pairs using the InParanoid program. This
      resulted in 2 642 187 pairwise ortholog groups in total. The orthology-based
      species relations are presented in an orthophylogram. InParanoid clusters contain
      one or more orthologs from each of the two species. Multiple orthologs in the
      same species, i.e. inparalogs, result from gene duplications after the species
      divergence. A new InParanoid website has been developed which is optimized for
      speed both for users and for updating the system. The XML output format has been
      improved for efficient processing of the InParanoid ortholog clusters.

PMID- 18055503
TI  - Evolution of quality and patient safety in Israel.

PMID- 18055502
TI  - Framework for primary care organizations: the importance of a structural domain.
AB  - PURPOSE: Conceptual frameworks for primary care have evolved over the last 40
      years, yet little attention has been paid to the environmental, structural and
      organizational factors that facilitate or moderate service delivery. Since
      primary care is now of more interest to policy makers, it is important that they
      have a comprehensive and balanced conceptual framework to facilitate their
      understanding and appreciation. We present a conceptual framework for primary
      care originally developed to guide the measurement of the performance of primary
      care organizations within the context of a large mixed-method evaluation of four
      types of models of primary care in Ontario, Canada. METHODS: The framework was
      developed following an iterative process that combined expert consultation and
      group meetings with a narrative review of existing frameworks, as well as trends
      in health management and organizational theory. RESULTS: Our conceptual framework
      for primary care has two domains: structural and performance. The structural
      domain describes the health care system, practice context and organization of the
      practice in which any primary care organization operates. The performance domain
      includes features of health care service delivery and technical quality of
      clinical care. CONCLUSION: As primary care evolves through demonstration projects
      and reformed delivery models, it is important to evaluate its structural and
      organizational features as these are likely to have a significant impact on
      performance.

PMID- 18055504
TI  - Relation of patients' experiences with individual physicians to malpractice risk.
AB  - OBJECTIVE: Patient care experience survey data might be useful for managing
      individual physician malpractice risk, but available evidence is limited. This
      study assesses whether patients' experiences with individual physicians, as
      measured by a validated survey, are associated with patient complaints and
      malpractice lawsuits. DESIGN: Random samples of active patients in physicians'
      panels, with sample sizes adequate to provide highly reliable, stable information
      about patients' experiences with each physician (n = 19 202, average respondents
      per physician = 119) were used to assess the relation of patient survey measures
      to malpractice risk. SETTING: A large multi-specialty physician organization in
      eastern Massachusetts, USA. PARTICIPANTS: Physicians providing care for at least
      5 years in adult primary care and select high-risk specialty departments between
      January 1996 and December 2005 (n = 161). MAIN OUTCOME MEASURES: Patient
      complaints (2001-05) and malpractice lawsuits (1996-2005). RESULTS: Compared to
      primary care physicians, high-risk specialists had a lower patient complaint rate
      (0.34 vs. 1.36 complaints per patient care full time equivalent; P < 0.001), but
      a higher lawsuit rate (0.09 vs. 0.05 lawsuits per patient care full time
      equivalent; P = 0.02). Irrespective of physician specialty, the quality of
      physician-patient interactions (IRR = 0.61; P < 0.001) and care coordination (IRR
      = 0.65; P < 0.001) were inversely associated with patient complaints. Patient
      survey measures were not associated with malpractice lawsuits. CONCLUSIONS: The
      results underscore the challenges organizations face when attempting to use
      patient survey data to manage individual physician medical malpractice risk.
      Because lawsuits are infrequent events, calibrating these validated patient
      survey measures to malpractice lawsuit risk will require large physician samples
      from diverse practices.

PMID- 18055505
TI  - A monoclonal antibody prevents aggregation of the NBD1 domain of the cystic
      fibrosis transmembrane conductance regulator.
AB  - The homozygous deletion of the phenylalanine at position 508 (DeltaPhe508) in the
      first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane
      conductance regulator (CFTR) is the most common CF-causing genetic defect. It has
      been proposed that the propensity of NBD1 to aggregate may lead to a lower
      display of the CFTR chloride channel to the cell membrane and to the disease,
      thus opening an avenue for the pharmacological development of CFTR folding
      correctors. Here, we show that a human monoclonal antibody fragment specific to
      the folded conformation of NBD1 inhibits the aggregation of NBD1 in vitro.
      However, in contrast to the previously published observations, we proved
      experimentally that NBD1 of wild-type and DeltaPhe508 version of CFTR display
      comparable propensities to aggregate in vitro and that the corresponding full
      length CFTR protein reaches the cell membrane with comparable efficiency in
      mammalian cell expression systems. On the basis of our results, the 'folding
      defect' hypothesis seems unlikely to represent the causal mechanism for the
      pathogenesis of CF. A solid understanding of how the DeltaPhe508 deletion leads
      to the disease represents an absolute requirement for the development of
      effective drugs against CF.

PMID- 18055506
TI  - Selective gene amplification.
AB  - We describe a system for directed evolution based on in vitro
      compartmentalisation in which amplification of a gene is coupled to the formation
      of product by the enzyme it encodes. This approach mimics the process of natural
      selection; 'fitter' genes--encoding more efficient enzymes--have more
      'offspring'. It allows selection for any activity so long as a product-specific
      ligand (e.g. an antibody) is available.

PMID- 18055508
TI  - Dose-related effects of red wine and alcohol on hemodynamics, sympathetic nerve
      activity, and arterial diameter.
AB  - The cardiovascular benefits of light to moderate red wine consumption often have
      been attributed to its polyphenol constituents. However, the acute dose-related
      hemodynamic, vasodilator, and sympathetic neural effects of ethanol and red wine
      have not been characterized and compared in the same individual. We sought to
      test the hypotheses that responses to one and two alcoholic drinks differ and
      that red wine with high polyphenol content elicits a greater effect than ethanol
      alone. Thirteen volunteers (24-47 yr; 7 men, 6 women) drank wine, ethanol, and
      water in a randomized, single-blind trial on three occasions 2 wk apart. One
      drink of wine and ethanol increased blood alcohol to 38 +/- 2 and 39 +/- 2 mg/dl,
      respectively, and two drinks to 72 +/- 4 and 83 +/- 3 mg/dl, respectively. Wine
      quadrupled plasma resveratrol (P < 0.001) and increased catechin (P < 0.03). No
      intervention affected blood pressure. One drink had no heart rate effect, but two
      drinks of wine increased heart rate by 5.7 +/- 1.6 beats/min; P < 0.001). Cardiac
      output fell 0.8 +/- 0.3 l/min after one drink of ethanol and wine (both P < 0.02)
      but increased after two drinks of ethanol (+0.8 +/- 0.3 l/min) and wine (+1.2 +/-
      0.3 l/min) (P < 0.01). One alcoholic drink did not alter muscle sympathetic nerve
      activity (MSNA), while two drinks increased MSNA by 9-10 bursts/min (P < 0.001).
      Brachial artery diameter increased after both one and two alcoholic drinks (P <
      0.001). No beverage augmented, and the second wine dose attenuated (P = 0.02),
      flow-mediated vasodilation. One drink of ethanol dilates the brachial artery
      without activating sympathetic outflow, whereas two drinks increase MSNA, heart
      rate, and cardiac output. These acute effects, which exhibit a narrow dose
      response, are not modified by red wine polyphenols.

PMID- 18055509
TI  - IP3 receptor-dependent Ca2+ release modulates excitation-contraction coupling in
      rabbit ventricular myocytes.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R)-dependent Ca(2+) signaling
      exerts positive inotropic, but also arrhythmogenic, effects on excitation
      contraction coupling (ECC) in the atrial myocardium. The role of IP(3)R-dependent
      sarcoplasmic reticulum (SR) Ca(2+) release in ECC in the ventricular myocardium
      remains controversial. Here we investigated the role of this signaling pathway
      during ECC in isolated rabbit ventricular myocytes. Immunoblotting of proteins
      from ventricular myocytes showed expression of both type 2 and type 3 IP(3)R at
      levels approximately 3.5-fold less than in atrial myocytes. In permeabilized
      myocytes, direct application of IP(3) (10 microM) produced a transient 21%
      increase in the frequency of Ca(2+) sparks (P < 0.05). This increase was
      accompanied by a 13% decrease in spark amplitude (P < 0.05) and a 7% decrease in
      SR Ca(2+) load (P < 0.05) and was inhibited by IP(3)R antagonists 2
      aminoethoxydiphenylborate (2-APB; 20 microM) and heparin (0.5 mg/ml). In intact
      myocytes endothelin-1 (100 nM) was used to stimulate IP(3) production and caused
      a 38% (P < 0.05) increase in the amplitude of action potential-induced (0.5 Hz,
      field stimulation) Ca(2+) transients. This effect was abolished by the IP(3)R
      antagonist 2-APB (2 microM) or by using adenoviral expression of an IP(3)
      affinity trap that buffers cellular IP(3). Together, these data suggest that in
      rabbit ventricular myocytes IP(3)R-dependent Ca(2+) release has positive
      inotropic effects on ECC by facilitating Ca(2+) release through ryanodine
      receptor clusters.

PMID- 18055510
TI  - Identity of the renin cell is mediated by cAMP and chromatin remodeling: an in
      vitro model for studying cell recruitment and plasticity.
AB  - The renin-angiotensin system (RAS) regulates blood pressure and fluid-electrolyte
      homeostasis. A key step in the RAS cascade is the regulation of renin synthesis
      and release by the kidney. We and others have shown that a major mechanism to
      control renin availability is the regulation of the number of cells capable of
      making renin. The kidney possesses a pool of cells, mainly in its vasculature but
      also in the glomeruli, capable of switching from smooth muscle to endocrine renin
      producing cells when homeostasis is threatened. The molecular mechanisms
      governing the ability of these cells to turn the renin phenotype on and off have
      been very difficult to study in vivo. We, therefore, developed an in vitro model
      in which cells of the renin lineage are labeled with cyan fluorescent protein and
      cells actively making renin mRNA are labeled with yellow fluorescent protein. The
      model allowed us to determine that it is possible to culture cells of the renin
      lineage for numerous passages and that the memory to express the renin gene is
      maintained in culture and can be reenacted by cAMP and chromatin remodeling
      (histone H4 acetylation) at the cAMP-responsive element in the renin gene.

PMID- 18055511
TI  - Pathophysiology of hypertension during preeclampsia: linking placental ischemia
      with endothelial dysfunction.
AB  - Studies over the last decade have provided exciting new insights into potential
      mechanisms underlying the pathogenesis of preeclampsia. The initiating event in
      preeclampsia is generally regarded to be placental ischemia/hypoxia, which in
      turn results in the elaboration of a variety of factors from the placenta that
      generates profound effects on the cardiovascular system. This host of molecules
      includes factors such as soluble fms-like tyrosine kinase-1, the angiotensin II
      type 1 receptor autoantibody, and cytokines such as tumor necrosis factor-alpha,
      which generate widespread dysfunction of the maternal vascular endothelium. This
      dysfunction manifests as enhanced formation of factors such as endothelin,
      reactive oxygen species, and augmented vascular sensitivity to angiotensin II.
      Alternatively, the preeclampsia syndrome may also be evidenced as decreased
      formation of vasodilators such as nitric oxide and prostacyclin. Taken together,
      these alterations cause hypertension by impairing renal pressure natriuresis and
      increasing total peripheral resistance. Moreover, the quantitative importance of
      the various endothelial and humoral factors that mediate vasoconstriction and
      elevation of arterial pressure during preeclampsia remains to be elucidated. Thus
      identifying the connection between placental ischemia/hypoxia and maternal
      cardiovascular abnormalities in hopes of revealing potential therapeutic regimens
      remains an important area of investigation and will be the focus of this review.

PMID- 18055512
TI  - Rosuvastatin provides pleiotropic protection against pulmonary hypertension,
      right ventricular hypertrophy, and coronary endothelial dysfunction in rats.
AB  - We recently reported that increased vascular endothelial nitric oxide production
      could protect against the development of monocrotaline (MCT)-induced pulmonary
      arterial hypertension (PAH) and right ventricular hypertrophy (RVH) in rats (32).
      The present study investigated whether the pleiotropic action of 3-hydroxy-3
      methylglutaryl-CoA reductase inhibitors in upregulating endothelial function
      could also protect against the MCT-induced end-organ damages. Rosuvastatin (2 mg
      kg(-1) day(-1) via oral gavage) or placebo was initiated 1 wk before or 1 wk
      after MCT (60 mg/kg ip) administration. One month after MCT, significant PAH
      developed in the placebo rats, which were accompanied by histological evidence of
      pulmonary vascular thickening and right ventricular hypertrophy. The coronary
      endothelial vasodilatory function, assessed with endothelial/nitric oxide
      dependent responses to acetylcholine and N(G)-nitro-L-arginine methyl ester (L
      NAME), was depressed, while the constrictory responses to known coronary
      constrictors was enhanced. In rats that received rosuvastatin treatment 1 wk
      before MCT administration, a significantly reduced PAH and RVH was observed, as
      well as reduced pulmonary vascular and right ventricular remodelings.
      Rosuvastatin 1-wk posttreatment had no effect on PAH, but inhibited RVH. Right
      coronary endothelial dysfunction, which was shown in placebo rats, was
      effectively prevented by both pre- and postrosuvastatin treatment, while this
      effect was more dramatic in the pretreated group. Left coronary endothelial
      function, which was not affected by MCT, also showed an upregulation by
      rosuvastatin. Taken together, our results demonstrated the pleiotropic protection
      of rosuvastatin against the development of PAH and RVH and confirmed our previous
      finding that the targeted preservation of coronary endothelial function and
      vasoactivity may provide a novel approach to protect against cardiac remodeling.

PMID- 18055507
TI  - International Union of Pharmacology. LXVIII. Mammalian bombesin receptors:
      nomenclature, distribution, pharmacology, signaling, and functions in normal and
      disease states.
AB  - The mammalian bombesin receptor family comprises three G protein-coupled
      heptahelical receptors: the neuromedin B (NMB) receptor (BB(1)), the gastrin
      releasing peptide (GRP) receptor (BB(2)), and the orphan receptor bombesin
      receptor subtype 3 (BRS-3) (BB(3)). Each receptor is widely distributed,
      especially in the gastrointestinal (GI) tract and central nervous system (CNS),
      and the receptors have a large range of effects in both normal physiology and
      pathophysiological conditions. The mammalian bombesin peptides, GRP and NMB,
      demonstrate a broad spectrum of pharmacological/biological responses. GRP
      stimulates smooth muscle contraction and GI motility, release of numerous GI
      hormones/neurotransmitters, and secretion and/or hormone release from the
      pancreas, stomach, colon, and numerous endocrine organs and has potent effects on
      immune cells, potent growth effects on both normal tissues and tumors, potent CNS
      effects, including regulation of circadian rhythm, thermoregulation; anxiety/fear
      responses, food intake, and numerous CNS effects on the GI tract as well as the
      spinal transmission of chronic pruritus. NMB causes contraction of smooth muscle,
      has growth effects in various tissues, has CNS effects, including effects on
      feeding and thermoregulation, regulates thyroid-stimulating hormone release,
      stimulates various CNS neurons, has behavioral effects, and has effects on spinal
      sensory transmission. GRP, and to a lesser extent NMB, affects growth and/or
      differentiation of various human tumors, including colon, prostate, lung, and
      some gynecologic cancers. Knockout studies show that BB(3) has important effects
      in energy balance, glucose homeostasis, control of body weight, lung development
      and response to injury, tumor growth, and perhaps GI motility. This review
      summarizes advances in our understanding of the biology/pharmacology of these
      receptors, including their classification, structure, pharmacology, physiology,
      and role in pathophysiological conditions.

PMID- 18055513
TI  - Age-related decrease in 15-lipoxygenase contributes to reduced vasorelaxation in
      rabbit aorta.
AB  - Rabbit 15-lipoxygenase-1 (15-LO-1) oxygenates arachidonic acid (AA) into 15
      hydroperoxyeicosatetraenoic acid, which is then converted to the vasodilatory 15
      hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) and 11,12,15
      trihydroxyeicosatrienoic acid (THETA). We studied the age-dependent expression of
      the 15-LO-1 in rabbit aorta and its effects on the synthesis of THETA, HEETA, and
      vasoactivity. Aortas of 1-wk-old rabbits express greater amounts of 15-LO-1 mRNA
      and protein compared with aortas of 4-, 8-, or 16-wk-old rabbits. The synthesis
      of THETA and HEETA in the rabbit aorta was also reduced with age. THETA synthesis
      was maximal in 1-wk-old aortas but decreased in aortas of 4- (42%), 8- (4%), and
      16-wk-old (1%) rabbits. Similarly, THETA and HEETA synthesis decreased with age
      in mesenteric arteries from 1-, 4-, 8-, and 16-wk-old rabbits. The maximum
      vasorelaxation response to acetylcholine (10(-6) M) in the presence of
      indomethacin and nitro-l-arginine decreased in the order of 1 wk (64.5 +/- 6.9%),
      4 wk (52.6 +/- 8.9%), 8 wk (53.0 +/- 9.4%), and 16 wk (33.3 +/- 6.6%). Similarly,
      the maximum relaxation to AA (3 x 10(-4) M) decreased with age in the order of 1
      wk (60.4 +/- 8.9%), 4 wk (56.3 +/- 5.8%), 8 wk (41.8 +/- 12.3%), and 16 wk (28.9
      +/- 1.6%). In contrast, the vasorelaxation to sodium nitroprusside was not
      significantly altered by age. These data indicate that aortic 15-LO-1 expression
      and activity are downregulated with aging in rabbits. This decrease is paralleled
      by the reduced synthesis of vasoactive THETA and HEETA and aortic relaxations to
      acetylcholine and AA.

PMID- 18055515
TI  - Diameter asymmetry of porcine coronary arterial trees: structural and functional
      implications.
AB  - The coronary vasculature is characterized by highly asymmetric diameters at
      bifurcations, which may be an important determinant of flow distribution. To
      facilitate accurate reconstruction of the coronary network for hemodynamic
      analysis, we introduce a statistical data set of the diameter asymmetry at
      bifurcations based on morphometric data of the porcine coronary arterial and
      venous trees. The bifurcation asymmetry data were represented by the diameter
      ratio of the daughters relative to mother vessel and by an area expansion ratio
      (AER) at each bifurcation. A novel asymmetry ratio matrix was introduced to
      describe the diameter asymmetry of daughters to mother vessels. The relations
      between AER and flow velocity, and asymmetry ratio matrix and flow distribution,
      were considered. The results indicate that the ratio of large daughter to mother
      vessel has a minimum value at order 5 (mean diameter of approximately 70 microm),
      whereas the ratio of small daughter to mother vessel decreases monotonically with
      increase in order number. The AER was found to be fairly uniform for larger
      vessels and to increase from order 5 toward the capillaries. At order 5, we
      observe a transition in asymmetric bifurcation pattern that may mark a
      hemodynamic transition from transmural to perfusion subnetworks. The functional
      implications of these structural transitions are considered.

PMID- 18055514
TI  - Multiple antiapoptotic targets of the PI3K/Akt survival pathway are activated by
      epoxyeicosatrienoic acids to protect cardiomyocytes from hypoxia/anoxia.
AB  - Epoxyeicosatrienoic acids (EETs) reduce infarction of the myocardium after
      ischemia-reperfusion injury to rodent and dog hearts mainly by opening
      sarcolemmal and mitochondrial potassium channels. Other mediators for the action
      of EET have been proposed, although no definitive pathway or mechanism has yet
      been reported. Using cultured cells from two rodent species, immortalized
      myocytes from a mouse atrial lineage (HL-1) and primary myocytes derived from
      neonatal rat hearts, we observed that pretreatment with EETs (1 microM of 14,15-,
      11,12-, or 8,9-EET) attenuated apoptosis after exposure to hypoxia and
      reoxygenation (H/R). EETs also preserved the functional beating of neonatal
      myocytes in culture after exposure to H/R. We demonstrated that EETs increased
      the activity of the prosurvival enzyme phosphatidylinositol 3-kinase (PI3K). In
      fact, cardiomyocytes pretreated with EET and exposed to H/R exhibited
      antiapoptotic changes in at least five downstream effectors of PI3K, protein
      kinase B (Akt), Bcl-x(L)/Bcl-2-associated death promoter, caspases-9 and -3
      activities, and the expression of the X-linked inhibitor of apoptosis, compared
      with vehicle-treated controls. The PI3K/Akt pathway is one of the strongest
      intracellular prosurvival signaling systems. Our studies show that EETs regulate
      multiple molecular effectors of this pathway. Understanding the targets of action
      of EET-mediated protection will promote the development of these fatty acids as
      therapeutic agents against cardiac ischemia-reperfusion.

PMID- 18055516
TI  - AT1 receptor antagonism attenuates target organ effects of salt excess in SHRs
      without affecting pressure.
AB  - Our recent studies have demonstrated that salt excess in the spontaneously
      hypertensive rat (SHR) produces a modestly increased arterial pressure while
      promoting marked myocardial fibrosis and structural damage associated with
      altered coronary hemodynamics and ventricular function. The present study was
      designed to determine the efficacy of an angiotensin II type 1 (AT(1)) receptor
      blocker (ARB) in the prevention of pressure increase and development of target
      organ damage from high dietary salt intake. Eight-week-old SHRs were given an 8%
      salt diet for 8 wk; their age- and gender-matched controls received standard
      chow. Some of the salt-loaded rats were treated concomitantly with ARB
      (candesartan; 10 mg kg(-1) day(-1)). The ARB failed to reduce the salt-induced
      rise in pressure, whereas it significantly attenuated left ventricular (LV)
      remodeling (mass and wall thicknesses), myocardial fibrosis (hydroxyproline
      concentration and collagen volume fraction), and the development of LV diastolic
      dysfunction, as shown by longer isovolumic relaxation time, decreased ratio of
      peak velocity of early to late diastolic waves, and slower LV relaxation (minimum
      first derivative of pressure over time/maximal LV pressure). Without affecting
      the increased pulse pressure by high salt intake, the ARB prevented the salt
      induced deterioration of coronary and renal hemodynamics but not the arterial
      stiffening or hypertrophy (pulse wave velocity and aortic mass index).
      Additionally, candesartan prevented the salt-induced increase in kidney mass
      index and proteinuria. In conclusion, the ARB given concomitantly with dietary
      salt excess ameliorated salt-related structural and functional cardiac and renal
      abnormalities in SHRs without reducing arterial pressure. These data clearly
      demonstrated that angiotensin II (via AT(1) receptors), at least in part,
      participated importantly in the pressure-independent effects of salt excess on
      target organ damage of hypertension.

PMID- 18055517
TI  - Deficiency of M2 muscarinic acetylcholine receptors increases susceptibility of
      ventricular function to chronic adrenergic stress.
AB  - Suppressed parasympathetic nervous system (PSNS) function has been found in a
      variety of cardiovascular diseases, such as hypertension, heart failure, and
      diabetes. However, whether impaired PSNS function plays a significant role in
      ventricular dysfunction remains to be investigated. Cardiac regulation by the
      PSNS is primarily mediated by the M(2) muscarinic acetylcholine receptor (M(2)
      AChR). In this study, we tested the hypothesis that lack of M(2)-AChR-mediated
      PSNS function may adversely impact cardiac ventricular function. Using M(2)-AChR
      knockout (KO) and wild-type (WT) mice, we found that the basal levels of heart
      rate and left ventricular function were similar in M(2)-AChR KO and WT mice. A
      bolus injection of isoproterenol (Iso) induced a greater increase in heart rate
      in M(2)-AChR KO mice than in WT mice. However, the responses of change in
      pressure over time (dP/dt) to Iso were similar in the two groups. After chronic
      infusion with Iso for 1 wk, the baseline values of left ventricular function were
      increased to similar extents in M(2)-AChR KO and WT mice. However, the M(2)-AChR
      KO mice exhibited impaired ventricular function, indicated as attenuated dP/dt
      and increased end-diastolic pressure, during an increase in cardiac afterload
      induced by a bolus injection of phenylephrine. Furthermore, chronic Iso infusion
      significantly increased matrix metalloproteinase (MMP) activity in the heart in
      M(2)-AChR KO mice. In primary culture of mixed neonatal rat cardiac fibroblast
      and cardiomyocytes, cotreatment with muscarinic agonist bethanechol reversed
      phenylephrine-induced increase in MMP-9 activation. These data suggest that M(2)
      AChR may mediate an inhibitory regulation on MMP function. The overall results
      from this study suggest that M(2)-AChR-mediated PSNS function may provide cardiac
      protection. Lack of this protective mechanism will increase the susceptibility of
      the heart to cardiac stresses.

PMID- 18055518
TI  - Oxygen regulation of arterial smooth muscle cell proliferation and survival.
AB  - The purpose of this study was to determine if hypoxia elicits different
      proliferative and apoptotic responses in systemic arterial smooth muscle cells
      incubated under conditions that do or do not result in cellular ATP depletion and
      whether these effects are relevant to vascular remodeling in vivo. Gene
      expression profiling was used to identify potential regulatory pathways. In human
      aortic smooth muscle cells (HASMCs) incubated at 3% O(2), proliferation and
      progression through the G1/S interphase are enhanced. Incubation at 1% O(2)
      reduced proliferation, delayed G1/S transition, increased apoptotic cell death,
      and is associated with mitochondrial membrane depolarization and reduced cellular
      ATP levels. In aorta and mesenteric artery from rats exposed to hypoxia (10%
      O(2), 48 h), both proliferation and apoptosis are increased, as are medial
      nuclear density and smooth muscle cell content. Although nuclear levels of
      hypoxia-inducible factor 1-alpha (HIF-1alpha) are increased to a similar extent
      in HASMCs incubated at 1 and 3% O(2), expression of tumor protein p53, its
      transcriptional target p21, as well as their regulatory factors and downstream
      effectors, are differentially affected under these two conditions, suggesting
      that the bidirectional effects of hypoxia are mediated by this pathway. We
      conclude that hypoxia induces a state of enhanced cell turnover through increased
      rates of both smooth muscle cell proliferation and death. This confers the
      ability to remodel the vasculature in response to changing tissue metabolic needs
      while avoiding the accumulation of mutations that may lead to malignant
      transformation or the formation of abnormal vascular structures.

PMID- 18055519
TI  - Temporal changes in cardiac force- and flow-generation capacity, loading
      conditions, and mechanical efficiency in streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus may result in impaired cardiac contractility, but the
      underlying mechanisms remain unclear. We aimed to investigate the temporal
      alterations in cardiac force- and flow-generation capacity and loading conditions
      as well as mechanical efficiency in the evolution of systolic dysfunction in
      streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats were
      randomized into control and STZ-induced diabetic groups. Invasive hemodynamic
      studies were done at 8, 16, and 22 wk post-STZ injection. Maximal systolic
      elastance (E(max)) and maximum theoretical flow (Q(max)) were assessed by curve
      fitting techniques, and ventriculoarterial coupling and mechanical efficiency
      were assessed by a single-beat estimation technique. In contrast to early
      occurring and persistently depressed E(max), Q(max) progressively increased with
      time but was decreased at 22 wk post-STZ injection, which temporally correlated
      with the changes in cardiac output. The favorable loading conditions enhanced
      stroke volume and Q(max), whereas ventriculoarterial uncoupling attenuated the
      cardiac mechanical efficiency in diabetic animals. The changes in E(max) and
      Q(max) are discordant during the progression of contractile dysfunction in the
      diabetic heart. In conclusion, our study showed that depressed Q(max) and cardiac
      mechanical efficiency, occurring preceding overt systolic heart failure, are two
      major determinants of deteriorating cardiac performance in diabetic rats.

PMID- 18055520
TI  - Astrocytes are a key conduit for upstream signaling of vasodilation during
      cerebral cortical neuronal activation in vivo.
AB  - Astrocytes play an important role in the coupling between neuronal activity and
      brain blood flow via their capacity to "sense" neuronal activity and transmit
      that information to parenchymal arterioles. Here we show another role for
      astrocytes in neurovascular coupling: the ability to act as a signaling conduit
      for the vitally important process of upstream vasodilation (represented by pial
      arterioles) during both excessive (seizure) and physiological (sciatic nerve
      stimulation) increases in cerebral cortical neuronal activity. The predominance
      of an astrocytic rather than a vascular route was indicated by data showing that
      pial arteriolar-dilating responses to neuronal activation were completely blocked
      following selective disruption of the superficial glia limitans, whereas
      interference with interendothelial signaling was without effect. Results also
      revealed contributions from connexin 43, implying a role for gap junctions and/or
      hemichannels in the signaling process and that signaling from the glia limitans
      to pial arterioles may involve a diffusible mediator.

PMID- 18055521
TI  - Coupling of endothelial injury and repair: an analysis using an in vivo
      experimental model.
AB  - The repair of the endothelium after inflammatory injury is essential to
      maintaining homeostasis. The link between inflammation-induced endothelial damage
      and repair has not been fully characterized in vivo. We have developed a rat
      model to evaluate the coupling of lipopolysaccharide (LPS)-induced endothelial
      injury and repair. Aortic endothelium injury was analyzed by both
      inmunohistochemistry and flow cytometry to quantify the number of endothelial
      cells and the percentage of apoptotic endothelial cells. We have also identified
      the percentage of circulating angiogenic cells capable of repairing the damaged
      endothelium. Erythropoietin was administered to inhibit LPS-induced endothelial
      apoptosis. Loss of the normal endothelial structure was observed in the aorta of
      the animals treated with LPS. Eight hours after LPS administration, the number of
      endothelial cells decreased by 40%, returning to normal after 24 h. There was a
      threefold increase in the percentage of circulating angiogenic cells, which did
      not return to normal levels until 48 h after LPS administration. Circulating
      angiogenic cell levels did not change when LPS-induced endothelial damage was
      prevented by erythropoietin. The endothelial injury caused by inflammation
      activates the mobilization of circulating angiogenic cells, thus completing
      endothelial repair. Inflammation without endothelial injury does not trigger the
      mobilization of circulating angiogenic cells.

PMID- 18055522
TI  - In vivo reactive oxygen species production induced by ischemia in muscle
      arterioles of mice: involvement of xanthine oxidase and mitochondria.
AB  - Reactive oxygen species (ROS) participate in tissue injury after ischemia
      reperfusion. Their implication in leukocyte adherence and increase in
      permeability at the venular side of the microcirculation have been reported, but
      very little is known about ROS production in arterioles. The objective of this
      work was to evaluate, in the arteriole wall in vivo, the temporal changes in
      superoxide anion production during ischemia and reperfusion and to identify the
      source of this production. Mouse cremaster muscle was exposed to 1 h of ischemia
      followed by 30 min of reperfusion, and superoxide anion production was assessed
      by a fluorescent probe, i.e., intracellular dihydroethidium oxidation. During
      ischemia, we found a significant increase in dihydroethidium oxidation; however,
      we observed no additional increase in fluorescence during the subsequent
      reperfusion. This phenomenon was significantly inhibited by pretreatment with
      superoxide dismutase. Allopurinol (xanthine oxidase inhibitor) or stigmatellin
      [Q(o)-site (oriented toward the intermembrane space) inhibitor of mitochondrial
      complex III] or simultaneous administration of these two inhibitors significantly
      reduced superoxide production during ischemia to 80%, 88%, and 72%, respectively,
      of that measured in the untreated ischemia-reperfusion group. By contrast, no
      significant inhibition was found when NADPH oxidase was inhibited by apocynin or
      when mitochondrial complex I or complex II was inhibited by rotenone or
      thenoyltrifluoroacetone. A significant increase in ROS was found with antimycin A
      [Q(i)-site (located in the inner membrane and facing the mitochondrial matrix)
      inhibitor of mitochondrial complex III]. We conclude that a significant increase
      in ROS production occurs during ischemia in the arteriolar wall. This increased
      production involves both a cytoplasmic source (i.e., xanthine oxidase) and the
      mitochondrial complex III at the Q(o) site.

PMID- 18055523
TI  - Cardiotrophin-1 stimulates intercellular adhesion molecule-1 and monocyte
      chemoattractant protein-1 in human aortic endothelial cells.
AB  - Intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1
      (MCP-1) play critical roles in mediating monocyte adhesion to the vascular
      endothelium and monocyte migration into the subendothelial regions of the
      vessels. Inasmuch as cardiotrophin-1 (CT-1), an IL-6-type cytokine, was expressed
      in human atherosclerotic plaque, we examined whether CT-1 induces monocyte
      adhesion and migration by stimulating gene and protein expressions of ICAM-1 and
      MCP-1 in human aortic endothelial cells (HAECs). Immunocytochemistry revealed
      that CT-1 increased intensity of ICAM-1 and MCP-1 immunoreactivity in HAECs.
      Adhesion assay and chemotaxis assay revealed that CT-1 increased human monocytic
      THP-1 cell adhesion to HAECs and promoted chemotaxis in THP-1 cells, which were
      attenuated by anti-ICAM-1 and anti-MCP-1 antibody, respectively. Western blot
      analysis showed that CT-1 increased phosphorylation of ERK1/2 MAP kinase, p38 MAP
      kinase, and Akt and that their inhibitors, PD-98059, SB-203580, and LY-294002,
      respectively, inhibited phosphorylation. RNase protection assay and ELISA
      demonstrated that CT-1 increased gene and protein expressions of ICAM-1 and MCP
      1. EMSA revealed that CT-1 enhanced NF-kappaB DNA-binding activity. CT-1-mediated
      upregulation of ICAM-1 and MCP-1 was suppressed by PD-98059, SB-203580, LY
      294002, and parthenolide. The present study demonstrates that CT-1 promotes
      monocyte adhesion and migration by stimulating ICAM-1 and MCP-1 through
      mechanisms that involve ERK1/2 MAP kinase, p38 MAP kinase, phosphatidylinositol 3
      kinase, and NF-kappaB pathways and suggests that CT-1 plays an important role in
      the pathophysiology of vascular inflammation and atherosclerosis.

PMID- 18055524
TI  - In silico study on the effects of IKur block kinetics on prolongation of human
      action potential after atrial fibrillation-induced electrical remodeling.
AB  - Pharmacological treatment with various antiarrhythmic agents for the termination
      or prevention of atrial fibrillation (AF) is not yet satisfactory. This is in
      part because the drugs may not be sufficiently selective for the atrium, and they
      often cause ventricular arrhythmias. The ultrarapid-delayed rectifying potassium
      current (I(Kur)) is found in the atrium but not in the ventricle, and it has been
      recognized as a potentially promising target for anti-AF drugs that would be
      without ventricular proarrhythmia. Several new agents that specifically block
      I(Kur) have been developed. They block I(Kur) in a voltage- and time-dependent
      manner. Here we use mathematical models of normal and electrically remodeled
      human atrial action potentials to examine the effects of the blockade kinetics of
      I(Kur) on atrial action potential duration (APD). It was found that after AF
      remodeling, an I(Kur) blocker with fast onset can effectively prolong APD at any
      stimulus frequency, whereas a blocker with slow onset prolongs APD in a frequency
      dependent manner only when the recovery is slow. The results suggest that the
      voltage and time dependence of I(Kur) blockade should be taken into account in
      the testing of anti-AF drugs. This modeling study suggests that a simple voltage
      clamp protocol with a short pulse of approximately 10 ms at 1 Hz may be useful to
      identify the effective anti-AF drugs among various I(Kur) blockers.

PMID- 18055525
TI  - Peripheral changes above and below injury level lead to prolonged vascular
      responses following high spinal cord injury.
AB  - Autonomic dysreflexia (AD) is a debilitating disorder producing episodes of
      extreme hypertension in patients with high-level spinal cord injury (SCI).
      Factors leading to AD include loss of vasomotor baroreflex control to regions
      below injury level, changes in spinal circuitry, and peripheral changes. The
      present study tested for peripheral changes below and above injury level 6 wk
      after a transection at the fourth thoracic spinal level. Changes in vascular
      conductance were recorded in the femoral, renal, brachial, and carotid arteries
      in response to intravenous injections of two alpha-adrenergic agonists,
      phenylephrine (PE; 0.03-100 microg/kg) and methoxamine (Meth; 1-300 microg/kg).
      Unlike PE, Meth is not subject to neuronal reuptake. Ganglionic blockade (0.6
      mg/kg chlorisondamine) was used to eliminate the central component of the
      cardiovascular response. After ganglionic blockade, SCI animals exhibited
      prolonged vasoconstriction in response to PE in all blood vessels measured
      compared with those in intact animals (all, P < 0.035). However, the PE dose
      response curves obtained after ganglionic blockade revealed no significant
      difference in the potency between the two groups (all, P > 0.06), indicating that
      the prolonged vasoconstriction was not due to supersensitivity to PE. In contrast
      to PE, vascular responses to Meth did not vary between intact and SCI groups (all
      P > 0.108). These results show the development of a widespread peripheral change
      producing prolonged vasoconstriction in response to PE, but not Meth, possibly
      due to reduced neuronal reuptake of PE after SCI. This is the first study to
      report such a change in blood vessels not only below but also above injury level.
      Interventions to correct this reduced reuptake may help limit the development of
      AD.

PMID- 18055526
TI  - Effect of heterogeneous APD restitution on VF organization in a model of the
      human ventricles.
AB  - The onset of ventricular fibrillation (VF) has been associated with steep action
      potential duration restitution in both clinical and computational studies.
      Recently, detailed clinical restitution properties in cardiac patients were
      reported showing a substantial degree of heterogeneity in restitution slopes at
      the epicardium of the ventricles. The aim of the present study was to investigate
      the effect of heterogeneous restitution properties in a three-dimensional model
      of the ventricles using these clinically measured restitution data. We used a
      realistic model of the human ventricles, including detailed descriptions of cell
      electrophysiology, ventricular anatomy, and fiber direction anisotropy. We
      extended this model by mapping the clinically observed epicardial restitution
      data to our anatomic representation using a diffusion-based algorithm.
      Restitution properties were then fitted by regionally varying parameters of the
      electrophysiological model. We studied the effects of restitution heterogeneity
      on the organization of VF by analyzing filaments and the distributions of
      excitation periods. We found that the number of filaments and the excitation
      periods were both dependent on the extent of heterogeneity. An increased level of
      heterogeneity leads to a greater number of filaments and a broader distribution
      of excitation periods, thereby increasing the complexity and dynamics of VF.
      Restitution heterogeneity may play an important role in providing a substrate for
      cardiac arrhythmias.

PMID- 18055527
TI  - Peroxynitrite inhibits the expression of G(i)alpha protein and adenylyl cyclase
      signaling in vascular smooth muscle cells.
AB  - We previously showed that S-nitroso-N-acetylpenicillamine, a nitric oxide donor,
      decreased the levels and functions of G(i)alpha proteins by formation of
      peroxynitrite (ONOO(-)) in vascular smooth muscle cells (VSMC). The present
      studies were undertaken to investigate whether ONOO(-) can modulate the
      expression of G(i)alpha protein and associated adenylyl cyclase signaling in
      VSMC. Treatment of A-10 and aortic VSMC with ONOO(-) for 24 h decreased the
      expression of G(i)alpha-2 and G(i)alpha-3, but not G(s)alpha, protein in a
      concentration-dependent manner; expression was restored toward control levels by
      (111)Mn-tetralis(benzoic acid porphyrin) and uric acid, but not by
      1H[1,2,4]oxadiazole[4,3-a]quinoxaline-1-one (ODQ) and KT-5823. cGMP levels were
      increased by approximately 50% and 150% by 0.1 and 0.5 mM ONOO(-), respectively,
      and attenuated toward control levels by ODQ. In addition, 0.5 mM ONOO(-)
      attenuated the inhibition of adenylyl cyclase by ANG II and C-type atrial
      natriuretic peptide (C-ANP(4-23)), as well as the inhibition of forskolin
      stimulated adenylyl cyclase activity by GTPgammaS, whereas, the G(s)-mediated
      stimulations were augmented. In addition, 0.5 mM ONOO(-) decreased
      phosphorylation of ERK1/2 and p38 MAP kinase and enhanced JNK phosphorylation but
      did not affect AKT1/3 phosphorylation. These results suggest that ONOO(-)
      decreased the expression of G(i) proteins and associated functions in VSMC
      through a cGMP-independent mechanism and may involve the MAP kinase signaling
      pathway.

PMID- 18055528
TI  - In vivo measurement of flow-mediated vasodilation in living rats using high
      resolution ultrasound.
AB  - In humans, endothelial vasodilator function serves as a surrogate marker for
      cardiovascular health and is measured as changes in conduit artery diameter after
      temporary ischemia [flow-mediated dilation (FMD)]. Here we present an FMD-related
      approach to study femoral artery (FA) vasodilation in anesthetized rats. Diameter
      and Doppler flow were monitored in the FA. Using high-resolution ultrasound (35
      MHz) and automated analysis software, we detected dose-dependent vasodilation
      using established endothelium-independent [intravenous nitroglycerin EC(50) = 3.3
      x 10(-6) mol/l, peak 21Delta% (SD 4)] and endothelium-dependent [intra-arterial
      acetylcholine EC(50) = 1.3 x 10(-6) mol/l, peak 27Delta% (SD 4)] pharmacological
      vasodilators. Wall shear stress induced by intra-aortic injection of adenosine
      and infusion of saline at increasing rates (1.5-4.5 ml/min) led to vasodilation
      at 1 to 2 min. Transient hindlimb ischemia by common iliac occlusion (5 min) led
      to reactive hyperemia with flow velocity and wall shear stress increase and was
      followed by FA dilation [16Delta% (SD 2)], the latter of which was completely
      abolished by nitric oxide synthase (NOS) inhibition with N(G)-monomethyl-L
      arginine [1Delta% (SD 2)]. FMD was significantly reduced in adult 20-24-wk-old
      animals compared with 9- to 10-wk-old animals, consistent with age-dependent
      endothelial dysfunction [16Delta% (SD 3) vs. 10Delta% (SD 3), P < 0.05]. Whereas
      FMD was completely NOS dependent in 9- to 10-wk-old animals, NOS-dependent
      mechanisms accounted for only half of the FMD in 20-24-wk-old animals, with the
      remainder being blocked by charybdotoxin and apamin, suggesting a contribution of
      endothelium-derived hyperpolarizing factor. To our knowledge, this is the first
      integrative physiological model to reproducibly study FMD of conduit arteries in
      living rats.

PMID- 18055530
TI  - Oligomerization of membrane-bound diphtheria toxin (CRM197) facilitates a
      transition to the open form and deep insertion.
AB  - Diphtheria toxin (DT) contains separate domains for receptor-specific binding,
      translocation, and enzymatic activity. After binding to cells, DT is taken up
      into endosome-like acidic compartments where the translocation domain inserts
      into the endosomal membrane and releases the catalytic domain into the cytosol.
      The process by which the catalytic domain is translocated across the endosomal
      membrane is known to involve pH-induced conformational changes; however, the
      molecular mechanisms are not yet understood, in large part due to the challenge
      of probing the conformation of the membrane-bound protein. In this work neutron
      reflection provided detailed conformational information for membrane-bound DT
      (CRM197) in situ. The data revealed that the bound toxin oligomerizes with
      increasing DT concentration and that the oligomeric form (and only the oligomeric
      form) undergoes a large extension into solution with decreasing pH that coincides
      with deep insertion of residues into the membrane. We interpret the large
      extension as a transition to the open form. These results thus indicate that as a
      function of bulk DT concentration, adsorbed DT passes from an inactive state with
      a monomeric dimension normal to the plane of the membrane to an active state with
      a dimeric dimension normal to the plane of the membrane.

PMID- 18055529
TI  - Cytoskeletal bundle mechanics.
AB  - The mechanical properties of cytoskeletal actin bundles play an essential role in
      numerous physiological processes, including hearing, fertilization, cell
      migration, and growth. Cells employ a multitude of actin-binding proteins to
      actively regulate bundle dimensions and cross-linking properties to suit
      biological function. The mechanical properties of actin bundles vary by orders of
      magnitude depending on diameter and length, cross-linking protein type and
      concentration, and constituent filament properties. Despite their importance to
      cell function, the molecular design principles responsible for this mechanical
      behavior remain unknown. Here, we examine the mechanics of cytoskeletal bundles
      using a molecular-based model that accounts for the discrete nature of
      constituent actin filaments and their distinct cross-linking proteins. A generic
      competition between filament stretching and cross-link shearing determines three
      markedly different regimes of mechanical response that are delineated by the
      relative values of two simple design parameters, revealing the universal nature
      of bundle-bending mechanics. In each regime, bundle-bending stiffness displays
      distinct scaling behavior with respect to bundle dimensions and molecular
      composition, as observed in reconstituted actin bundles in vitro. This mechanical
      behavior has direct implications on the physiological bending, buckling, and
      entropic stretching behavior of cytoskeletal processes, as well as reconstituted
      actin systems. Results are used to predict the bending regimes of various in vivo
      cytoskeletal bundles that are not easily accessible to experiment and to generate
      hypotheses regarding implications of the isolated behavior on in vivo bundle
      function.

PMID- 18055531
TI  - Heterogeneity in desiccated solutions: implications for biostabilization.
AB  - Biopreservation processes such as freezing and drying inherently introduce
      heterogeneity. We focused on exploring the mechanisms responsible for
      heterogeneity in isothermal, diffusively dried biopreservation solutions that
      contain a model protein. The biopreservation solutions used contained trehalose
      (a sugar known for its stabilization effect) and salts (LiCl, NaCl, MgCl2, and
      CaCl2). Performing Fourier transform infrared spectroscopy analysis on the
      desiccated droplets, spatial distributions of the components within the dried
      droplet, as well as their specific interactions, were investigated. It was
      established that the formation of multiple thermodynamic states was induced by
      the spatial variations in the cosolute concentration gradients, directly
      affecting the final structure of the preserved protein. The spatial distribution
      gradients were formed by two competing flows that formed within the drying
      droplet: a dominant peripheral flow, induced by contact line pinning, and the
      Marangoni flow, induced by surface tension gradients. It was found that the
      changes in cosolute concentrations and drying conditions affected the spatial
      heterogeneity and stability of the product. It was also found that trehalose and
      salts had a synergistic stabilizing effect on the protein structure, which
      originated from destructuring of the vicinal water, which in turn mediated the
      interactions of trehalose with the protein. This interaction was observed by the
      change in the glycosidic CO, and the CH stretch vibrations of the trehalose
      molecule.

PMID- 18055532
TI  - Osmotic stress and viscous retardation of the Na,K-ATPase ion pump.
AB  - The transport function of the Na pump (Na,K-ATPase) in cellular ion homeostasis
      involves both nucleotide binding reactions in the cytoplasm and alternating
      aqueous exposure of inward- and outward-facing ion binding sites. An osmotically
      active, nonpenetrating polymer (poly(ethyleneglycol); PEG) and a modifier of the
      aqueous viscosity (glycerol) were used to probe the overall and partial enzymatic
      reactions of membranous Na,K-ATPase from shark salt glands. Both inhibit the
      steady-state Na,K-ATPase as well as Na-ATPase activity, whereas the K(+)
      dependent phosphatase activity is little affected by up to 50% of either. Both
      Na,K-ATPase and Na-ATPase activities are inversely proportional to the viscosity
      of glycerol solutions in which the membranes are suspended, in accordance with
      Kramers' theory for strong coupling of fluctuations at the active site to solvent
      mobility in the aqueous environment. PEG decreases the affinity for Tl(+) (a
      congener for K(+)), whereas glycerol increases that for the nucleotides ATP and
      ADP in the presence of NaCl but has little effect on the affinity for Tl(+). From
      the dependence on osmotic stress induced by PEG, the aqueous activation volume
      for the Na,K-ATPase reaction is estimated to be approximately 5-6 nm(3) (i.e.,
      approximately 180 water molecules), approximately half this for Na-ATPase, and
      essentially zero for p-nitrophenol phosphatase. The change in aqueous hydrated
      volume associated with the binding of Tl(+) is in the region of 9 nm(3). Analysis
      of 15 crystal structures of the homologous Ca-ATPase reveals an increase in PEG
      inaccessible water space of approximately 22 nm(3) between the E(1)-nucleotide
      bound forms and the E(2)-thapsigargin forms, showing that the experimental
      activation volumes for Na,K-ATPase are of a magnitude comparable to the overall
      change in hydration between the major E(1) and E(2) conformations of the Ca
      ATPase.

PMID- 18055534
TI  - Properly interpreting lipid-protein specificities in pulmonary surfactant.

PMID- 18055535
TI  - Discrimination of class I cyclobutane pyrimidine dimer photolyase from blue light
      photoreceptors by single methionine residue.
AB  - DNA photolyase recognizes ultraviolet-damaged DNA and breaks improperly formed
      covalent bonds within the cyclobutane pyrimidine dimer by a light-activated
      electron transfer reaction between the flavin adenine dinucleotide, the electron
      donor, and cyclobutane pyrimidine dimer, the electron acceptor. Theoretical
      analysis of the electron-tunneling pathways of the DNA photolyase derived from
      Anacystis nidulans can reveal the active role of the protein environment in the
      electron transfer reaction. Here, we report the unexpectedly important role of
      the single methionine residue, Met-353, where busy trafficking of electron
      tunneling currents is observed. The amino acid conservation pattern of Met-353 in
      the homologous sequences perfectly correlates with experimentally verified
      annotation as photolyases. The bioinformatics sequence analysis also suggests
      that the residue plays a pivotal role in biological function. Consistent findings
      from different disciplines of computational biology strongly suggest the pivotal
      role of Met-353 in the biological function of DNA photolyase.

PMID- 18055536
TI  - Measuring and modeling chloride-hydroxyl exchange in the Guinea-pig ventricular
      myocyte.
AB  - Protons are powerful modulators of cardiac function. Their intracellular
      concentration is regulated by sarcolemmal ion transporters that export or import
      H+-ions (or their ionic equivalent: HCO3-, OH-). One such transporter, which
      imports H+-equivalents, is a putative Cl-/OH- exchanger (CHE). A strong candidate
      for CHE is SLC26A6 protein, a product of the SLC26A gene family of anion
      transporters, which has been detected in murine heart. SLC26A6 protein is
      suggested to be an electrogenic 1Cl-/2OH-(2HCO3-) exchanger. Unfortunately, there
      is insufficient characterization of cardiac CHE against which the properties of
      heterologously expressed SLC26A6 can be matched. We therefore investigated the
      proton, Cl-, and voltage dependence of CHE activity in guinea-pig ventricular
      myocytes, using voltage-clamp, intracellular pH fluorescence, and mathematical
      modeling techniques. We find that CHE activity is tightly regulated by
      intracellular and extracellular pH, is voltage-insensitive over a wide range (+/
      80 mV), and displays substrate dependence suggestive of electroneutral 1Cl-/1OH-
      exchange. These properties exclude electrogenic SLC26A6 as sole contributor to
      CHE. Either the SLC26A6 product in heart is electroneutral, or CHE comprises at
      least two transporters with oppositely balanced voltage sensitivity.
      Alternatively, CHE may comprise an H+-Cl- coinflux system, which cannot be
      distinguished kinetically from an exchanger. Irrespective of ionic mechanism,
      CHE's pH sensitivity helps to define resting intracellular pH, and hence basal
      function in the heart.

PMID- 18055537
TI  - SRC family kinases and receptors: analysis of three activation mechanisms by
      dynamic systems modeling.
AB  - Src family kinases (SFKs) interact with a number of cellular receptors. They
      participate in diverse signaling pathways and cellular functions. Most of the
      receptors involved in SFK signaling are characterized by similar modes of
      regulation. This computational study discusses a general kinetic model of SFK
      receptor interaction. The analysis of the model reveals three major ways of SFK
      activation: release of inhibition by C-terminal Src kinase, weakening of the
      inhibitory intramolecular phosphotyrosine-SH2 interaction, and amplification of a
      stimulating kinase activity. The SFK model was then extended to simulate
      interaction with growth factor and T-cell receptors. The modular SFK signaling
      system was shown to adapt to the requirements of specific signaling contexts and
      yield qualitatively different responses in the different simulated environments.
      The model also provides a systematic overview of the major interactions between
      SFKs and various cellular signaling systems and identifies their common
      properties.

PMID- 18055538
TI  - Agnostic particle tracking for three-dimensional motion of cellular granules and
      membrane-tethered bead dynamics.
AB  - The ability to detect biological events at the single-molecule level provides
      unique biophysical insights. Back-focal-plane laser interferometry is a promising
      technique for nanoscale three-dimensional position measurements at rates far
      beyond the capability of standard video. We report an in situ calibration
      technique for back-focal-plane, low-power (nontrapping) laser interferometry. The
      technique does not rely on any a priori model or calibration knowledge, hence the
      name "agnostic". We apply the technique to track long-range (up to 100 microm)
      motion of a variety of particles, including magnetic beads, in three-dimensions
      with high spatiotemporal resolution ( approximately 2 nm, 100 micros). Our
      tracking of individual unlabeled vesicles revealed a previously unreported
      grouping of mean-squared displacement curves at short timescales (<10 ms). Also,
      tracking functionalized magnetic beads attached to a live cell membrane revealed
      an anchorage-dependent nonlinear response of the membrane. The software-based
      technique involves injecting small perturbations into the probe position by
      driving a precalibrated specimen-mounting stage while recording the quadrant
      photodetector signals. The perturbations and corresponding quadrant photodetector
      signals are analyzed to extract the calibration parameters. The technique is
      sufficiently fast and noninvasive that the calibration can be performed on-the
      fly without interrupting or compromising high-bandwidth, long-range tracking of a
      particle.

PMID- 18055539
TI  - Structure and thermotropic behavior of the Staphylococcus aureus lipid lysyl
      dipalmitoylphosphatidylglycerol.
AB  - We have characterized the structural and thermotropic properties of one of the
      most important lipids in the cell membrane of Staphylococcus aureus, lysyl
      dipalmitoylphosphatidylglycerol (lysyl-DPPG). applying differential scanning
      calorimetry and small- and wide-angle x-ray scattering. Microcalorimetry revealed
      that under physiological conditions (phosphate buffer, 20 mM NaPi, 130 mM NaCl,
      pH 7.4), the synthetic lysyl-DPPG resembles the features of the parent
      dipalmitoylphosphatidylglycerol (DPPG) with respect to its melting behavior.
      However, in contrast to DPPG, lowering the pH did not significantly affect the
      main transition temperature ( approximately 40 degrees C) of lysyl-DPPG, which
      can be explained by its difference in protonization because of the lysine group.
      X-ray experiments yielded the first information on chain packing and morphology
      of lysyl-DPPG. We found that lysyl-DPPG forms an interdigitated lamellar phase
      below the chain-melting transition. This can be explained by the large headgroup
      area of lysyl-DPPG as a result of its charged lysine group, especially if the
      headgroup is arranged parallel to the bilayer plane. Additionally, lysyl-DPPG
      degradation products, such as lysine and free fatty acids, had significant
      influences on the melting behavior and led to a multicomponent melting
      transition. Our results indicate that the degradation of lysyl-DPPG takes place
      mainly during the hydration process but also depends on lipid storage time, pH,
      and thermal treatment. Detailed temperature-resolved experiments at pH 5.0
      demonstrated the formation of a lamellar gel phase with tilted hydrocarbon chains
      and a ripple phase, coexisting with the interdigitated lysyl-DPPG bilayers.

PMID- 18055540
TI  - Interfacial polar interactions affect gramicidin channel kinetics.
AB  - Critical to biological processes such as secretion and transport, protein-lipid
      interactions within the membrane and at the membrane-water interface still raise
      many questions. Here we examine the role of lipid headgroups in these
      interactions by using gramicidin A (gA) channels in planar bilayers as a probe.
      We show that although headgroup demethylation from phosphatidylcholine (DOPC) to
      phosphatidylethanolamine decreases the lifetime of gA channels by an order of
      magnitude in accordance with the currently accepted hydrophobic mismatch
      mechanism, our findings with diether-DOPC suggest the importance of the headgroup
      peptide interactions. According to our x-ray diffraction measurements, this lipid
      has the same hydrophobic thickness as DOPC but increases gA lifetime by a factor
      of 2. Thus we demonstrate that peptide-headgroup interactions may dominate over
      the effect of hydrophobic mismatch in regulating protein function.

PMID- 18055541
TI  - Protection against human immunodeficiency virus type 1 Tat neurotoxicity by
      Ginkgo biloba extract EGb 761 involving glial fibrillary acidic protein.
AB  - Human immunodeficiency virus (HIV)-1 Tat protein is an important pathogenic
      factor in HIV-associated neuropathogenesis. Despite recent progress, the
      molecular mechanisms underlying Tat neurotoxicity are still not completely
      understood. However, few therapeutics have been developed to specifically target
      HIV infection in the brain. Recent development of an inducible brain-specific Tat
      transgenic mouse model has made it possible to define the mechanisms of Tat
      neurotoxicity and evaluate anti-neuroAIDS therapeutic candidates in the context
      of a whole organism. Herein, we demonstrate that administration of EGb 761, a
      standardized formulation of Ginkgo biloba extract, markedly protected Tat
      transgenic mice from Tat-induced developmental retardation, inflammation, death,
      astrocytosis, and neuron loss. EGb 761 directly down-regulated glial fibrillary
      acidic protein (GFAP) expression at both protein and mRNA levels. This down
      regulation was, at least in part, attributable to direct effects of EGb 761 on
      the interactions of the AP1 and NF-kappaB transcription factors with the GFAP
      promoter. Most strikingly, Tat-induced neuropathological phenotypes including
      macrophage/microglia activation, central nervous system infiltration of T
      lymphocytes, and oxidative stress were significantly alleviated in GFAP-null/Tat
      transgenic mice. Taken together, these results provide the first evidence to
      support the potential for clinical use of EGb 761 to treat HIV-associated
      neurological diseases. Moreover, these findings suggest for the first time that
      GFAP activation is directly involved in Tat neurotoxicity, supporting the notion
      that astrocyte activation or astrocytosis may directly contribute to HIV
      associated neurological disorders.

PMID- 18055542
TI  - Cholangiocytes with mesenchymal features contribute to progressive hepatic
      fibrosis of the polycystic kidney rat.
AB  - The polycystic kidney (PCK) rat is an animal model of Caroli's disease with
      congenital hepatic fibrosis, in which the mechanism of progressive hepatic
      fibrosis remains unknown. This study aimed to clarify the mechanism of hepatic
      fibrosis of the PCK rat from the viewpoint of the contribution of pathological
      cholangiocytes. In liver sections of the PCK rats, intrahepatic bile ducts were
      constituted by two different phenotypes: bile ducts lined by cuboidal-shaped and
      flat-shaped cholangiocytes. The flat-shaped cholangiocytes showed reduced
      immunohistochemical expression of the biliary epithelial marker cytokeratin 19
      and positive immunoreactivity for vimentin and fibronectin. When cultured
      cholangiocytes of the PCK rat were treated with transforming growth factor (TGF)
      beta1, a potent inducer of epithelial-mesenchymal transition, induction of
      vimentin, fibronectin, and collagen expression occurred in the PCK
      cholangiocytes. Although the TGF-beta1 treatment reduced cytokeratin 19
      expression, the epithelial cell features characterized by the expression of E
      cadherin and zonula occludens-1 was maintained, and alpha-smooth muscle actin
      expression was not induced in the cholangiocytes. Cholangiocytes of the PCK rat
      may acquire mesenchymal features in response to TGF-beta1 and participate in
      progressive hepatic fibrosis by producing extracellular matrix molecules, which
      seems to be a different event from epithelial-mesenchymal transition.

PMID- 18055543
TI  - Chronic oxidative stress causes amplification and overexpression of ptprz1
      protein tyrosine phosphatase to activate beta-catenin pathway.
AB  - Ferric nitrilotriacetate induces oxidative renal tubular damage via Fenton
      reaction, which subsequently leads to renal cell carcinoma (RCC) in rodents.
      Here, we used gene expression microarray and array-based comparative genomic
      hybridization analyses to find target oncogenes in this model. At the common
      chromosomal region of amplification (4q22) in rat RCCs, we found ptprz1, a
      tyrosine phosphatase (also known as protein tyrosine phosphatase zeta or receptor
      tyrosine phosphatase beta) highly expressed in the RCCs. Analyses revealed
      genomic amplification up to eightfold. Despite scarcity in the control kidney,
      the amounts of PTPRZ1 were increased in the kidney after 3 weeks of oxidative
      stress, and mRNA levels were increased 16 approximately 552-fold in the RCCs.
      Network analysis of the expression revealed the involvement of the beta-catenin
      pathway in the RCCs. In the RCCs, dephosphorylated beta-catenin was translocated
      to nuclei, resulting in the expression of its target genes cyclin D1, c-myc, c
      jun, fra-1, and CD44. Furthermore, knockdown of ptprz1 with small interfering RNA
      (siRNA), in FRCC-001 and FRCC-562 cell lines established from the induced RCCs,
      decreased the amounts of nuclear beta-catenin and suppressed cellular
      proliferation concomitant with a decrease in the expression of target genes.
      These results demonstrate that chronic oxidative stress can induce genomic
      amplification of ptprz1, activating beta-catenin pathways without the involvement
      of Wnt signaling for carcinogenesis. Thus, iron-mediated persistent oxidative
      stress confers an environment for gene amplification.

PMID- 18055544
TI  - The monocyte chemoattractant protein-1/cognate CC chemokine receptor 2 system
      affects cell motility in cultured human podocytes.
AB  - In crescentic glomerulonephritis (GN), monocyte chemoattractant protein-1 (MCP-1)
      is overexpressed within the glomeruli, and MCP-1 blockade has renoprotective
      effects. Adult podocytes are in a quiescent state, but acquisition of a
      migratory/proliferative phenotype has been described in crescentic GN and
      implicated in crescent formation. The cognate CC chemokine receptor 2 (CCR2), the
      MCP-1 receptor, is expressed by other cell types besides monocytes and has been
      implicated in both cell proliferation and migration. We investigated whether MCP
      1 binding to CCR2 can induce a migratory/proliferative response in cultured
      podocytes. MCP-1 binding to CCR2 enhanced podocyte chemotaxis/haptotaxis in a
      concentration-dependent manner and had a modest effect on cell proliferation.
      Closure of a wounded podocyte monolayer was delayed by CCR2 blockade, and CCR2
      was overexpressed at the wound edge, suggesting a role for CCR2 in driving
      podocyte migration. Immunohistochemical analysis of kidney biopsies from patients
      with crescentic GN demonstrated CCR2 expression in both podocytes and cellular
      crescents, confirming the clinical relevance of our in vitro findings. In
      conclusion, the MCP-1/CCR2 system is functionally active in podocytes and may be
      implicated in the migratory events triggered by podocyte injury in crescentic GN
      and other glomerular diseases.

PMID- 18055545
TI  - Lipoprotein receptor-related protein-1 mediates amyloid-beta-mediated cell death
      of cerebrovascular cells.
AB  - Inefficient clearance of A beta, caused by impaired blood-brain barrier crossing
      into the circulation, seems to be a major cause of A beta accumulation in the
      brain of late-onset Alzheimer's disease patients and hereditary cerebral
      hemorrhage with amyloidosis Dutch type. We observed association of receptor for
      advanced glycation end products, CD36, and low-density lipoprotein receptor
      (LDLR) with cerebral amyloid angiopathy in both Alzheimer's disease and
      hereditary cerebral hemorrhage with amyloidosis Dutch type brains and increased
      low-density lipoprotein receptor-related protein-1 (LRP-1) expression by
      perivascular cells in cerebral amyloid angiopathy. We investigated if these A
      beta receptors are involved in A beta internalization and in A beta-mediated cell
      death of human cerebrovascular cells and astrocytes. Expression of both the LRP-1
      and LDLR by human brain pericytes and leptomeningeal smooth muscle cells, but not
      by astrocytes, increased on incubation with A beta. Receptor-associated protein
      specifically inhibited A beta-mediated up-regulation of LRP-1, but not of LDLR,
      and receptor-associated protein also decreased A beta internalization and A beta
      mediated cell death. We conclude that especially LRP-1 and, to a minor extent,
      LDLR are involved in A beta internalization by and A beta-mediated cell death of
      cerebral perivascular cells. Although perivascular cells may adapt their A beta
      internalization capacity to the levels of A beta present, saturated LRP-1/LDLR
      mediated uptake of A beta results in degeneration of perivascular cells.

PMID- 18055546
TI  - Myeloperoxidase is critically involved in the induction of organ damage after
      renal ischemia reperfusion.
AB  - In this study the role of myeloperoxidase (MPO) in a murine (C57BL/6) model of
      ischemia and reperfusion (I/R)-induced renal failure was investigated. The renal
      function after I/R was analyzed in MPO-deficient (Mpo(-/-)) mice and compared
      with wild-type (WT) controls. A significant reduction in renal function loss
      (blood urea nitrogen) was observed after 24 hours of reperfusion of ischemically
      damaged kidneys in Mpo(-/-) mice compared with I/R WT controls (I/R Mpo(-/-) =
      31.3 +/- 1.7 mmol/L versus I/R WT = 42.8 +/- 2.1 mmol/L, sham = 7.0 +/- 0.5
      mmol/L; P = 0.003). The early reperfusion phase (2 hours of reperfusion) was
      characterized by a substantial increase in apoptosis and early complement
      activation, surprisingly similar in Mpo(-/-) and WT mice. Improved renal function
      in Mpo(-/-) mice after extended reperfusion was accompanied by a reduced
      neutrophil influx (P = 0.017) compared with WT controls. Activation and
      deposition of complement was not significantly reduced in Mpo(-/-) mice compared
      with WT controls after 24 hours of reperfusion, indicating no specific in vivo
      role for MPO in activating complement after renal I/R. Taken together, these
      results demonstrated an important contribution of MPO in the induction of organ
      damage after renal I/R by influencing critical factors such as neutrophil
      extravasation but not complement activation.

PMID- 18055547
TI  - Indoleamine 2,3-dioxygenase (IDO): the antagonist of type I interferon-driven
      skin inflammation?
AB  - Recent studies have provided evidence that a type I interferon (IFN)-driven
      immune response might play an important role in the pathogenesis of lichen planus
      (LP), an inflammatory disorder of the skin of unclear etiology. Plasmacytoid
      dendritic cells in affected skin from LP have been proposed to produce IFN
      alpha/beta locally, which leads to the expression of IFN-inducible chemokines
      such as IP10/CXCL10 in the epidermis. This chemokine recruits chemokine receptor
      CXCR3-expressing T-lymphocytes into the skin via CXCR3/IP10 interactions.
      Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan and suppresses T
      cell proliferation, is induced by IFNs and other inflammatory cytokines. We show
      that type I IFN-mediated skin disorders, such as LP, strongly express IDO in
      lesional skin. This expression closely correlates to the expression of the highly
      specific type I IFN marker MxA. We further demonstrate that the IDO+ cells in LP
      are large myeloid CD11c+S100+CD68(-) dendritic cells. Accordingly, CD11c+ antigen
      presenting cells significantly up-regulate IDO gene expression and intracellular
      IDO protein expression after stimulation with IFN-alpha in vitro. These findings
      reveal that both proinflammatory and counterregulatory mechanisms are operative
      in cutaneous lesions of LP. We propose that the balance of these mechanisms may
      be involved in the pathogenesis of this disorder.

PMID- 18055548
TI  - Probing the effects of stress mediators on the human hair follicle: substance P
      holds central position.
AB  - Stress alters murine hair growth, depending on substance P-mediated neurogenic
      inflammation and nerve growth factor (NGF), a key modulator of hair growth
      termination (catagen induction). Whether this is of any relevance in human hair
      follicles (HFs) is completely unclear. Therefore, we have investigated the
      effects of substance P, the central cutaneous prototypic stress-associated
      neuropeptide, on normal, growing human scalp HFs in organ culture. We show that
      these prominently expressed substance P receptor (NK1) at the gene and protein
      level. Organ-cultured HFs responded to substance P by premature catagen
      development, down-regulation of NK1, and up-regulation of neutral endopeptidase
      (degrades substance P). This was accompanied by mast cell degranulation in the HF
      connective tissue sheath, indicating neurogenic inflammation. Substance P down
      regulated immunoreactivity for the growth-promoting NGF receptor (TrkA), whereas
      it up-regulated NGF and its apoptosis- and catagen-promoting receptor (p75NTR).
      In addition, MHC class I and beta2-microglobulin immunoreactivity were up
      regulated and detected ectopically, indicating collapse of the HF immune
      privilege. In conclusion, we present a simplistic, but instructive, organ culture
      assay to demonstrate sensitivity of the human HF to key skin stress mediators.
      The data obtained therewith allow one to sketch the first evidence-based
      biological explanation for how stress may trigger or aggravate telogen effluvium
      and alopecia areata.

PMID- 18055549
TI  - Induction of tau pathology by intracerebral infusion of amyloid-beta -containing
      brain extract and by amyloid-beta deposition in APP x Tau transgenic mice.
AB  - Alzheimer's disease presents morphologically with senile plaques, primarily made
      of extracellular amyloid-beta (A beta) deposits, and neurofibrillary lesions,
      which consist of intracellular aggregates of hyperphosphorylated tau protein. To
      study the in vivo induction of tau pathology, dilute brain extracts from aged A
      beta-depositing APP23 transgenic mice were intracerebrally infused in young
      B6/P301L tau transgenic mice. Six months after the infusion, tau pathology was
      induced in the injected hippocampus but also in brain regions well beyond the
      injection sites such as the entorhinal cortex and amygdala, areas with neuronal
      projection to the injection site. No or only modest tau induction was observed
      when brain extracts from aged nontransgenic control mice and aged tau-depositing
      B6/P301L transgenic mice were infused. To further study A beta-induced tau
      lesions B6/P301L tau transgenic mice were crossed with APP23 mice. Although A
      beta deposition in double-transgenic mice did not differ from single APP23
      transgenic mice, double-transgenic mice revealed increased tau pathology compared
      to single B6/P301L tau transgenic mice predominately in areas with high A beta
      plaque load. The present results suggest that both extract-derived A beta species
      and deposited fibrillary A beta can induce the formation of tau neurofibrillary
      pathology. The observation that infused A beta can trigger the tau pathology in
      the absence of A beta deposits provides an explanation for the discrepancy
      between the neuroanatomical location of A beta deposits and the development and
      spreading of tau lesions in Alzheimer's disease brain.

PMID- 18055550
TI  - Loss of partitioning-defective-3/isotype-specific interacting protein (par
      3/ASIP) in the elongating spermatid of RA175 (IGSF4A/SynCAM)-deficient mice.
AB  - IGSF4a/RA175/SynCAM (RA175) and junctional adhesion molecules (Jams) are members
      of the immunoglobulin superfamily with a PDZ-binding domain at their C termini.
      Deficiency of Ra175 (Ra175(-/-)) as well as Jam-C deficiency (Jam-C(-/-)) causes
      the defect of the spermatid differentiation, oligo-astheno-teratozoospermia.
      Ra175(-/-) elongating spermatids fail to mature further, whereas Jam-C(-/-) round
      spermatids lose cell polarity, and most of Jam-C(-/-) elongated spermatids are
      completely lost. RA175 and Jam-C seem to have similar but distinct functional
      roles during spermatid differentiation. Here we show that the cell polarity
      protein Par-3 with PDZ domains, a binding partner of Jams, is one of the
      associated proteins of the cytoplasmic region of RA175 in testis. Par-3 and Jam-C
      are partly co-localized with RA175 in the elongating and elongated spermatids;
      their distributions overlapped with that of RA175 on the tips of the dorsal
      region of the head of the elongating spermatid (steps 9 to 12) in the wild type.
      In the Ra175(-/-) elongating spermatid, Par-3 was absent, and Jam-C was absent or
      abnormally localized. The RA175 formed a ternary complex with Jam-C via
      interaction with Par-3. The lack of the ternary complex in the Ra175(-/-)
      elongating spermatid may cause the defect of the specialized adhesion structures,
      resulting in the oligo-astheno-teratozoospermia.

PMID- 18055551
TI  - Amelioration of coxsackievirus B3-mediated myocarditis by inhibition of tissue
      inhibitors of matrix metalloproteinase-1.
AB  - Coxsackievirus B3 (CVB3) is a major cause of acute myocarditis, a serious
      condition that is refractory to treatment. Myocardial damage results in tissue
      remodeling that, if too extensive, may contribute to disease. Remodeling is
      achieved by extracellular proteolysis mediated by the matrix metalloproteinases
      (MMPs), and MMP activity is counterbalanced by tissue inhibitors of MMPs (TIMPs).
      We show herein that TIMP-1 expression is induced in the myocardium by CVB3
      infection. Surprisingly, TIMP-1 knockout mice exhibited a profound attenuation of
      myocarditis, with increased survival. The amelioration of disease in TIMP-1
      knockout mice was not attributable to either an altered T-cell response to the
      virus or to reduced viral replication. These data led us to propose a novel
      function for TIMP-1: its highly localized up-regulation might arrest the MMP
      dependent migration of inflammatory cells at sites of infection, thereby
      anatomically focusing the adaptive immune response. The benefits of TIMP-1
      blockade in treating viral myocarditis were confirmed by administering, to wild
      type animals, TIMP-1-specific siRNA or polyclonal antisera, both of which
      diminished CVB3-induced myocarditis. These unexpected findings indicate that
      increased TIMP-1 expression exacerbates, rather than ameliorates, CVB3-induced
      myocarditis and, thus, that TIMP-1 may represent a target for the treatment of
      virus-induced heart disease.

PMID- 18055552
TI  - Nox1 expression determines cellular reactive oxygen and modulates c-fos-induced
      growth factor, interleukin-8, and Cav-1.
AB  - Increased cellular reactive oxygen species (ROS) can act as mitogenic signals in
      addition to damaging DNA and oxidizing lipids and proteins, implicating ROS in
      cancer development and progression. To analyze the effects of Nox1 expression and
      its relation to cellular ROS and signal transduction involved in cellular
      proliferation, Nox1RNAi constructs were transfected into DU145 prostate cancer
      cells overexpressing Nox1, causing decreased Nox1 message and protein levels in
      the Nox1RNAi cell lines. Increased ROS and tumor growth in the Nox1
      overexpressing DU145 cells were reversed in the presence of the Nox1RNAi.
      Analysis and comparison of the message levels in the overexpression and RNAi
      cells demonstrated that Nox1 overexpression leads to changes in message levels of
      a variety of proteins including c-fos-induced growth factor, interleukin-8, and
      Cav-1. Finally, we found that Nox1 protein overexpression is an early event in
      the development of prostate cancer using a National Cancer Institute prostate
      cancer tissue microarray (CPCTR). Tumor (86%) was significantly more likely to
      have Nox1 staining than benign prostate tissue (62%) (P = 0.0001). These studies
      indicate that Nox1 overexpression may function as a reversible signal for
      cellular proliferation with relevance for a common human tumor.

PMID- 18055553
TI  - Deletion of integrin-linked kinase from skeletal muscles of mice resembles
      muscular dystrophy due to alpha 7 beta 1-integrin deficiency.
AB  - Integrin-linked kinase (Ilk) is a serine/threonine kinase and an adaptor protein
      that links integrins to the actin cytoskeleton and to a number of signaling
      pathways involved in integrin action. We hypothesized that Ilk may act as an
      important effector of integrins in skeletal muscle, where these receptors provide
      a critical link between the sarcolemma and the extracellular matrix. Using the
      cre/lox system, we deleted Ilk from skeletal muscles of mice. The resulting
      mutants developed a progressive muscular dystrophy with multiple degenerating and
      regenerating muscle fibers, increased central nuclei, and endomysial fibrosis.
      These defects were widespread but were most severe near myofascial junctions
      where Ilk mutants showed displacement of focal adhesion-related proteins,
      including vinculin, paxillin, focal adhesion kinase, dystrophin, and the alpha 7
      beta 1D-integrin subunits. Distal ends of mutant muscle fibers appeared
      irregular, and there was restructuring of the actin cytoskeleton. These findings
      resemble those seen in humans and mice lacking the alpha 7-integrin subunit and
      suggest that Ilk may act as a cytoplasmic effector of alpha 7 beta1-integrin in
      the pathogenesis of these deficiencies.

PMID- 18055554
TI  - Interleukin-4 does not influence development of hypercholesterolemia or
      angiotensin II-induced atherosclerotic lesions in mice.
AB  - Interleukin-4 (IL-4) has been detected in both human and mouse atherosclerotic
      lesions, although its effects on the development of the disease are undefined. We
      determined the role of IL-4 in the most commonly used murine models of
      atherosclerosis by defining the effects of exogenous delivery and genetic
      deficiency of this cytokine on both hypercholesterolemia and AngII-induced
      atherosclerosis in apolipoprotein E (apoE)(-/-) mice and different dietary
      stimuli in low-density lipoprotein (LDL) receptor(-/-) mice. Exogenous
      administration of IL-4 (1.1 ng g(-1) day(-1) i.p. for 30 days) into female apoE(
      /-) mice had no effect on lesion size or composition in mice fed normal or
      saturated fat diets. Also, IL-4 deficiency had no significant effect on the size
      or composition of atherosclerotic lesions in two vascular areas of male and
      female apoE(-/-) mice fed either a normal or saturated fat diet. IL-4 deficiency
      was also studied in age-matched male mice infused with AngII (1000 ng kg(-1) min(
      1)) for 28 days. Whereas AngII infusion augmented atherosclerotic lesion
      formation, IL-4 deficiency did not influence atherosclerotic lesion size or
      composition. Finally, different dietary stimuli also had no effect on
      atherosclerotic lesion size in female LDL receptor(-/-) mice. These data
      demonstrate that IL-4 does not significantly influence the development of
      atherosclerotic lesions in apoE(-/-) mice of either gender or in female LDL
      receptor(-/-) mice, irrespective of the mode of induction of atherosclerosis.

PMID- 18055555
TI  - Polyunsaturated fatty acids induce alpha-synuclein-related pathogenic changes in
      neuronal cells.
AB  - The misfolding and aggregation of normally soluble proteins has emerged as a key
      feature of several neurodegenerative diseases. In Parkinson's disease,
      progressive loss of dopaminergic neurons is accompanied by polymerization of the
      cytoplasmic protein alpha-synuclein (alphaS) into filamentous inclusions found in
      neuronal somata (Lewy bodies) and dendrites (Lewy neurites). Similar alphaS
      aggregates occur in cortical neurons in dementia with Lewy bodies. Numerous
      reports now indicate that alphaS can interact with lipids. We previously found
      that treating dopaminergic cells expressing alphaS with polyunsaturated fatty
      acids (PUFAs) induced the formation of soluble, sodium dodecyl sulfate-stable
      oligomers whereas treatment with saturated fatty acids did not. Here, we examine
      the relevance of alphaS-PUFA interactions to the development of Parkinson's
      disease-like cytopathology. Exposure of alphaS-overexpressing dopaminergic or
      neuronal cell lines to physiological levels of a PUFA induced the formation of
      proteinaceous inclusions in the cytoplasm. Kinetic experiments indicated that
      PUFA-induced soluble oligomers of alphaS precede these Lewy-like inclusions.
      Importantly, we found that alphaS oligomers were associated with cyto-toxicity,
      whereas the development of Lewy-like inclusions appeared to be protective. We
      conclude that alterations in PUFA levels can lead to aggregation of alphaS and
      subsequent deposition into potentially cyto-toxic oligomers that precede
      inclusions in dopaminergic cells.

PMID- 18055556
TI  - The role of macrophage migration inhibitory factor in the cascade of events
      leading to reperfusion-induced inflammatory injury and lethality.
AB  - Ischemia and reperfusion (I/R) injury is associated with a systemic inflammatory
      response, characterized by intense tumor necrosis factor (TNF)-alpha production
      and TNF-alpha-dependent tissue injury. Macrophage migration inhibitory factor
      (MIF) is a potent proinflammatory cytokine that may induce TNF-alpha release and
      play an important role in innate immune and inflammatory responses. The aim of
      this work was to assess whether MIF was involved the inflammatory cascade and
      injury that follows intestinal I/R. To this end, wild-type (WT) and MIF-deficient
      (MIF(-/-)) mice underwent 60 minutes of ischemia followed by 60 minutes of
      reperfusion, after which they were culled for the assessment of inflammatory
      parameters. I/R was accompanied by an increase in circulating levels of MIF and
      an increase of vascular permeability, hemorrhage, and production of TNF-alpha in
      the intestine and lungs. The latter parameters were markedly suppressed in
      reperfused MIF(-/-) mice, and this was associated with decreased lethality (80%
      in WT versus 20% in MIF(-/-) mice). Interestingly, the reperfusion-associated
      neutrophil accumulation in the intestine and lungs was similar in WT and MIF(-/-)
      mice. Leukocytes isolated from lungs of MIF(-/-) mice were less activated, as
      assessed by their response to zymosan in a luminol-enhanced chemiluminescence
      assay. In conclusion, our results suggest that MIF plays an important role in the
      cascade of events leading to TNF-alpha production and reperfusion-induced tissue
      injury and lethality in mice.

PMID- 18055557
TI  - Protein kinase C delta regulates airway mucin secretion via phosphorylation of
      MARCKS protein.
AB  - Mucin hypersecretion is a major pathological feature of many respiratory
      diseases, yet cellular mechanisms regulating secretion of mucin have not been
      fully elucidated. Previously, we reported that mucin hypersecretion induced by
      human neutrophil elastase involves activation of protein kinase C (PKC),
      specifically the delta-isoform (PKC delta). Here, we further investigated the
      role of PKC delta in mucin hypersecretion using both primary human bronchial
      epithelial cells and the human bronchial epithelial 1 cell line as in vitro model
      systems. Phorbol-12-myristate-13-acetate (PMA)-induced mucin hypersecretion was
      significantly attenuated by rottlerin, a PKC delta-selective inhibitor. Rottlerin
      also reduced PMA- or human neutrophil elastase-induced phosphorylation of
      myristoylated alanine-rich C kinase substrate (MARCKS) protein in these cells.
      Both secretion and MARCKS phosphorylation were significantly enhanced by the PKC
      delta activator bryostatin 1. A dominant-negative PKC delta construct (pEGFP
      N1/PKC delta K376R) transfected into human bronchial epithelial 1 cells
      significantly attenuated both PMA-induced mucin secretion and phosphorylation of
      MARCKS, whereas transfection of a wild-type construct increased PKC delta and
      enhanced mucin secretion and MARCKS phosphorylation. Similar transfections of a
      dominant-negative or wild-type PKC epsilon construct did not affect either mucin
      secretion or MARCKS phosphorylation. The results suggest that PKC delta plays an
      important role in mucin secretion by airway epithelium via regulation of MARCKS
      phosphorylation.

PMID- 18055558
TI  - Gastrointestinal disease in simian immunodeficiency virus-infected rhesus
      macaques is characterized by proinflammatory dysregulation of the interleukin-6
      Janus kinase/signal transducer and activator of transcription3 pathway.
AB  - Gastrointestinal disease and inflammation are common sequelae of human and simian
      immunodeficiency virus (SIV) infection. Nevertheless, the molecular mechanisms
      that lead to gastrointestinal dysfunction remain unclear. We investigated
      regulation of the interleukin (IL)-6-JAK-STAT3 pathway in jejunum and colon,
      collected at necropsy, from 10 SIV-infected macaques with diarrhea (group 1), 10
      non-SIV-infected macaques with diarrhea (group 2), and 7 control uninfected
      macaques (group 3). All group 1 and 2 macaques had chronic diarrhea, wasting, and
      colitis, but group 1 animals had more frequent and severe lesions in the jejunum.
      A significant increase in IL-6 and SOCS-3 gene expression along with constitutive
      STAT3 activation was observed in the colon of all group 1 and 2 macaques and in
      the jejunum of only group 1 macaques compared to controls. Further, in colon,
      histopathology severity scores correlated significantly with IL-6 (groups 1 and
      2) and SOCS-3 (group 2) gene expression. In jejunum, a similar correlation was
      observed only in group 1 animals. Phosphorylated STAT3 (p-STAT3) was localized to
      lymphocytes (CD3+) and macrophages (CD68+), with fewer CD3+ lymphocytes
      expressing p-STAT3 in group 1 macaques. Despite high SOCS-3 expression, STAT3
      remained constitutively active, providing a possible explanation for persistent
      intestinal inflammation and immune activation that may favor viral replication
      and disease pro-gression.

PMID- 18055559
TI  - Angiogenic growth factor synergism in a murine tissue engineering model of
      angiogenesis and adipogenesis.
AB  - De novo tissue generation stimulated by three angiogenic growth factors
      administered in a factorial design was studied in an in vivo murine tissue
      engineering chamber. A silicone chamber was implanted around the epigastric
      pedicle and filled with Matrigel with 100 ng/ml of recombinant mouse vascular
      endothelial growth factor-120 (VEGF120), recombinant human basic fibroblastic
      growth factor (FGF-2), or recombinant rat platelet-derived growth factor-BB (PDGF
      BB) added as single, double, or triple combinations. Angiogenesis, supporting
      tissue ingrowth, and adipogenesis were assessed at 2 and 6 weeks by
      immunohistochemistry and morphometry. At 2 weeks angiogenesis was synergistically
      enhanced by VEGF120 + FGF-2 (P = 0.019). FGF-2 (P = 0.008) and PDGF-BB (P = 0.01)
      significantly increased connective tissue/inflammatory cell infiltrate
      (macrophages, pericytes, and preadipocytes) in double and triple combinations
      compared with control. At 6 weeks sequential addition of growth factors increased
      the percent volume of adipose tissue (P < 0.0005, each main effect), with a
      synergistic increase in adipose tissue in combination treatments (P < 0.0005).
      Groups containing 300 ng/ml of single growth factors produced significantly less
      adipose tissue than the triple growth factor combination (P < 0.0005, VEGF120 and
      PDGF-BB; P < 0.001, FGF-2). In conclusion, angiogenic growth factor combinations
      increased early angiogenesis and cell infiltration resulting in synergistically
      increased adipose tissue growth at 6 weeks. Two way and higher level synergies
      are likely to be important in therapeutic applications of angiogenic growth
      factors.

PMID- 18055560
TI  - Biosystematics and conservation: a case study with two enigmatic and uncommon
      species of Crassula from New Zealand.
AB  - BACKGROUND AND AIMS: Crassula hunua and C. ruamahanga have been taxonomically
      controversial. Here their distinctiveness is assessed so that their taxonomic and
      conservation status can be clarified. METHODS: Populations of these two species
      were analysed using morphological, chromosomal and DNA sequence data. KEY
      RESULTS: It proved impossible to differentiate between these two species using 12
      key morphological characters. Populations were found to be chromosomally variable
      with 11 different chromosome numbers ranging from 2n = 42 to 2n = 100. Meiotic
      behaviour and levels of pollen stainability were both variable. Phylogenetic
      analyses showed that differences exist in both nuclear and plastid DNA sequences
      between individual plants, sometimes from the same population. CONCLUSIONS: The
      results suggest that these plants are a species complex that has evolved through
      interspecific hybridization and polyploidy. Their high levels of chromosomal and
      DNA sequence variation present a problem for their conservation.

PMID- 18055561
TI  - The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated
      with subjective responses to tobacco.
AB  - Neuronal nicotinic acetylcholine receptors have been implicated in various
      measures of nicotine dependence. In this paper, we present findings from an
      exploratory study of single nucleotide polymorphisms (SNPs) in the CHRNB3 and
      CHRNA6 genes with tobacco and alcohol phenotypes, including frequency of use and
      three subjective response factors occurring shortly after initiation of use.
      Subjects were 1056 ethnically diverse adolescents ascertained from clinical and
      community settings. The most significant associations were found between two
      CHRNB3 SNPs (rs4950 and rs13280604) and the three subjective response factors to
      initial tobacco use. These findings were replicated in a separate community
      sample of 1524 families participating in the National Longitudinal Study of
      Adolescent Health. Both CHRNB3 SNPs were found to be associated with similar
      measures of subjective response to tobacco. These results indicate that early
      subjective response to nicotine may be a valuable endophenotype for genetic
      studies aimed at uncovering genes contributing to nicotine use and addiction.

PMID- 18055562
TI  - A novel, putative gain-of-function haplotype at SLC6A4 associates with obsessive
      compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric illness with
      strong segregation data indicative of major genetic contributions. Association
      analyses of common functional variants of the serotonin transporter gene
      (SLC6A4), a long-standing OCD candidate, have so far been inconsistent. Here, we
      set out to investigate the role of additional functional SLC6A4 loci in OCD. We
      describe a common, functional C > T single nucleotide polymorphism, rs25532,
      located less than 150 nucleotides centromeric of the serotonin transporter-linked
      polymorphic region indel known as 5-HTTLPR. The minor allele of rs25532
      significantly decreased luciferase reporter gene expression levels by 15-80%,
      depending on 5-HTTLPR allele background and cell type. Haplotype-based testing of
      rs25532 and all other known non-coding functional SLC6A4 variants revealed a
      highly significant omnibus association with OCD in a large case-control sample.
      Remarkably, the haplotype significantly overrepresented in probands contained the
      higher-expressing allele at each locus, supporting the notion of increased
      serotonin transporter functioning being pathogenetically involved in OCD.
      Conditional haplotype analyses with the software WHAP revealed that this
      association is primarily driven by 5-HTTLPR, rs25532 and rs16965628. Our results
      contribute to a better understanding of SLC6A4 expression genetics and provide a
      functional haplotype framework for future serotonin-related studies.

PMID- 18055563
TI  - "Mid-term," "long-term," and other terms: making sense of clinical follow-up.

PMID- 18055564
TI  - Can proton MR spectroscopic and perfusion imaging differentiate between
      neoplastic and nonneoplastic brain lesions in adults?
AB  - BACKGROUND AND PURPOSE: Noninvasive diagnosis of brain lesions is important for
      the correct choice of treatment. Our aims were to investigate whether 1) proton
      MR spectroscopic imaging ((1)H-MRSI) can aid in differentiating between tumors
      and nonneoplastic brain lesions, and 2) perfusion MR imaging can improve the
      classification. MATERIALS AND METHODS: We retrospectively examined 69 adults with
      untreated primary brain lesions (brain tumors, n = 36; benign lesions, n = 10;
      stroke, n = 4; demyelination, n = 10; and stable lesions not confirmed on
      pathologic examination, n = 9). MR imaging and (1)H-MRSI were performed at 1.5T
      before biopsy or treatment. Concentrations of N-acetylaspartate (NAA), creatine
      (Cr), and choline (Cho) in the lesion were expressed as metabolite ratios and
      were normalized to the contralateral hemisphere. Dynamic susceptibility contrast
      enhanced perfusion MR imaging was performed in a subset of patients (n = 32);
      relative cerebral blood volume (rCBV) was evaluated. Discriminant function
      analysis was used to identify variables that can predict inclusion in the
      neoplastic or nonneoplastic lesion groups. Receiver operator characteristic (ROC)
      analysis was used to compare the discriminatory capability of (1)H-MRSI and
      perfusion MR imaging. RESULTS: The discriminant function analysis correctly
      classified 84.2% of original grouped cases (P < .0001), on the basis of NAA/Cho,
      Cho(norm), NAA(norm), and NAA/Cr ratios. MRSI and perfusion MR imaging had
      similar discriminatory capabilities in differentiating tumors from nonneoplastic
      lesions. With cutoff points of NAA/Cho < or =0.61 and rCBV > or =1.50
      (corresponding to diagnosis of the tumors), a sensitivity of 72.2% and
      specificity of 91.7% in differentiating tumors from nonneoplastic lesions were
      achieved. CONCLUSION: These results suggest a promising role for (1)H-MRSI and
      perfusion MR imaging in the distinction between brain tumors and nonneoplastic
      lesions in adults.

PMID- 18055565
TI  - Maintaining subspecialty certification in neuroradiology.

PMID- 18055566
TI  - Digital forensics and the American Journal of Neuroradiology.

PMID- 18055567
TI  - Successful treatment of primary plasma cell leukaemia by allogeneic stem cell
      transplantation from haploidentical sibling.
AB  - Primary plasma cell leukaemia (PCL) is a rare, aggressive neoplasm of plasma cell
      dyscrasia. Conventional chemotherapy is usually ineffective, with an overall
      survival of only 8 months. Here, we describe a 42-year-old man with primary PCL,
      who was successfully treated with haploidentical (2-HLA loci mismatched)
      haematopoietic stem-cell transplantation (HSCT). To overcome the human leukocyte
      antigen (HLA) disparity, in vivo T-cell purging by the pre-transplant
      administration of antithymocyte globulin followed by a conventional prophylactic
      treatment against graft-versus-host disease (GVHD) resulted in an avoidance of
      severe GVHD as well as infectious complications. The patient has maintained
      complete remission for 13 months after haploidentical HSCT, indicating that a
      graft-versus-PCL effect might be preserved. Haploidentical HSCT can be a
      potentially curative treatment for patients with primary PCL who do not have an
      HLA-identical donor.

PMID- 18055568
TI  - Impairment of human NK cell cytotoxic activity and cytokine release by cigarette
      smoke.
AB  - NK cells play essential roles in innate host defense against microbial infections
      and tumor surveillance. Although evidence suggests that smoking has adverse
      effects on the immune system, little is known about whether smoking compromises
      NK cell effector functions. In this study, we show that cigarette smoke
      conditioned medium (SCM) dose-dependently inhibits in vitro IFN-gamma production
      by polyinosinic:polycytidylic acid (poly I:C)-activated PBMC and NK cells
      isolated from nonsmoking individuals. Similarly, SCM attenuated poly I:C-induced
      TNF-alpha production by PBMC and NK cells. The inhibitory effect of cigarette
      smoke on TNF-alpha production was reversible. PBMC and NK cells isolated from
      smokers displayed significant reduction of IFN-gamma and TNF-alpha secretions
      compared with nonsmokers in response to poly I:C activation. We further observed
      that SCM attenuated NK cell cytotoxic activity, which was associated with
      decreased up-regulation of perforin expression. Attenuated cytotoxic activity was
      also observed in PBMCs isolated from smokers. Finally, anti-IL-12 mAb-blocking
      data revealed that an attenuation of IFN-gamma production by PBMC was indirect,
      likely via attenuation of IL-12 production, and the effect on NK cells was IL-12
      independent. Our data indicate that cigarette smoke compromises function of human
      NK cells. This may contribute to a higher incidence of viral infections and
      cancer among smokers.

PMID- 18055569
TI  - Lyn-coupled LacCer-enriched lipid rafts are required for CD11b/CD18-mediated
      neutrophil phagocytosis of nonopsonized microorganisms.
AB  - The integrin CD11b/CD18 plays a central role in neutrophil phagocytosis. Although
      CD11b/CD18 binds a wide range of ligands, including C3bi and beta-glucan, and
      transmits outside-in signaling, the mechanism of this signaling responsible for
      phagocytosis remains obscure. Here, we report that lactosylceramide (LacCer)
      enriched lipid rafts are required for CD11b/CD18-mediated phagocytosis of
      nonopsonized zymosans (NOZs) by human neutrophils. Anti-CD11b and anti-LacCer
      antibodies inhibited the binding of NOZs to neutrophils and the phagocytosis of
      NOZs. During phagocytosis of NOZ, CD11b and LacCer were accumulated and
      colocalized in the actin-enriched phagocytic cup regions. Immunoprecipitation
      experiments suggested that CD11b/CD18 was mobilized into the LacCer-enriched
      lipid rafts during phagocytosis of NOZs. DMSO-treated, neutrophil-like HL-60
      cells (D-HL-60 cells) lacking Lyn-coupled, LacCer-mediated signaling showed
      little phagocytosis of NOZs. However, loading of D-HL-60 cells with C24 fatty
      acid chain-containing LacCer (C24-LacCer) reconstructed functional Lyn
      associated, LacCer-enriched lipid rafts, and restored D-HL-60 cell NOZ phagocytic
      activity, which was inhibited by anti-LacCer and anti-CD11b antibodies. Lyn
      knockdown by small interfering RNA blocked the effect of C24:1-LacCer loading on
      D-HL-60 cell phagocytosis of NOZs. CD11b/CD18 activation experiments indicated
      phosphorylation of LacCer-associated Lyn by activation of CD11b. Taken together,
      these observations suggest that CD11b activation causes translocation of
      CD11b/CD18 into Lyn-coupled, LacCer-enriched lipid rafts, allowing neutrophils to
      phagocytose NOZs via CD11b/CD18.

PMID- 18055571
TI  - Late-onset proptosis with Baerveldt glaucoma implants.

PMID- 18055570
TI  - Stromal cell-derived factor 1-alpha (SDF)-induced human T cell chemotaxis becomes
      phosphoinositide 3-kinase (PI3K)-independent: role of PKC-theta.
AB  - Stromal cell-derived factor 1alpha (SDF-1alpha) is the exclusive ligand for the
      chemokine receptor CXCR4. This receptor plays a pivotal role in immune responses,
      the pathogenesis of infection such as HIV, and cellular trafficking. However, the
      signaling mechanisms regulating SDF-driven T cell migration are not well defined.
      In this study, we determined the role of PI3K and protein kinase C- theta (PKC
      theta) in SDF-induced human T cell migration in fresh versus cultured T cells.
      Purified human T cells (fresh vs. 48 h in media, unstimulated or activated by
      anti-CD3+anti-CD28) were used. Western blots showed that SDF induced phospho-(p)
      Akt [threonine (Thr)308 and serine 473], a proxy for PI3K activity, in fresh
      cells and p-PKC-theta in 48 h unstimulated cells. LY294002 (PI3K inhibitor)
      reduced SDF-induced chemotaxis in fresh cells by 51%, whereas it minimally
      affected chemotaxis in 48 h unstimulated or activated cells. However, a specific
      PKC-theta inhibitor, pseudosubstrate for PKC-theta, reduced chemotaxis in 48 h
      unstimulated and stimulated T cells by 72% and 87%, respectively. Thus,
      chemotaxis becomes independent of PI3K signaling in human T cells cultured for 48
      h. Under these conditions, PKC-theta is phosphorylated (Thr538) by SDF, and
      chemotaxis becomes largely PKC-theta-dependent.

PMID- 18055572
TI  - Recovery of visual field and acuity after removal of epiretinal and inner
      limiting membranes.
AB  - BACKGROUND: Visual acuity serves as only a rough gauge of macular function. The
      aim therefore was to ascertain whether central an assessment of the central
      visual field afforded a closer insight into visual function after removal of
      epiretinal membranes and Infracyanine-Green- or Trypan-Blue-assisted peeling of
      the inner limiting membrane. PATIENTS AND METHODS: Fourty-three patients
      undergoing pars-plana vitrectomy for the removal of epimacular membranes and dye
      assisted peeling of the inner limiting membrane using either Infracyanine Green
      (n = 29; group 1) or Trypan Blue (n = 14; group 2) were monitored prospectively
      for 12 months. Preoperatively, and 1, 6 and 12 months postoperatively, distance
      and reading visual acuities were evaluated; the central visual field was assessed
      by automated static perimetry. RESULTS: Twelve months after surgery, distance and
      reading visual acuities had improved in both groups, but to a significant degree
      only in Trypan-Blue-treated eyes. The difference between the two groups was not
      significant. Likewise at this juncture, the mean size of the visual-field defect
      remained unchanged in Trypan-Blue-treated eyes (preoperative: 4.3 (SD 2.1) dB; 12
      months: 4.0 (2.1) dB (p = 0.15)), but had increased in Infracyanine-Green-treated
      ones (from 5.3 (3.7) dB to 8.0 (5.2) dB (p = 0.027)). CONCLUSION: Unlike visual
      acuity, the central visual field had deteriorated in Infracyanine-Green-treated
      eyes but not in Trypan-Blue-treated eyes 12 months after surgery. Hence, as a
      predictor of functional outcome, testing of the central visual field may be a
      more sensitive gauge than visual acuity. Furthermore, Infracyanine Green may have
      a chronic and potentially clinically relevant effect on the macula which is not
      reflected in the visual acuity.

PMID- 18055573
TI  - Peel and peel again.
AB  - AIM: To determine if the internal limiting membrane (ILM) was present in the
      epiretinal membrane (ERM) when we deliberately tried to perform a "double peel"
      for macular pucker. METHODS: Pars-plana vitrectomy and a "double peel" were
      carried out. The ERM and ILM were stained with Trypan Blue and peeled separately
      over the same area. The amount of ERM present in ILM specimens and the amount of
      ILM present in ERM specimens were evaluated by histological examination. RESULTS:
      Seventeen eyes in 17 patients were included. It was possible to double peel in
      all cases. Five of 17 ERM specimens (29%) contained ILM fragments. When ILM was
      present on the ERM, it represented less than 50% of the sample. One ILM specimen
      was lost as result of an administrative error; of the remaining 16 specimens,
      residual ERM was found in six, and cellular remnants were observed on the
      vitreous surface in a further six of the ILMs. Clinically, no recurrence of ERM
      was found. CONCLUSION: ILM was present in some ERM specimens seemingly over the
      same area that an intact ILM was subsequently peel. We speculate that the ILM in
      the ERM represent a secondary basement membrane and that the surgical plane of
      dissection for most ERM peel is between the ERM and the native ILM, making it
      feasible to double peel routinely.

PMID- 18055574
TI  - The prevalence, severity and risk factors for pterygium in central Myanmar: the
      Meiktila Eye Study.
AB  - AIMS: To determine the prevalence, severity and risk factors associated with
      pterygium in adults in central Myanmar. METHODS: Population-based, cross
      sectional survey of the people 40 years and over residing in rural Myanmar.
      Pterygium was graded for severity (T1 to T3) by visibility of episcleral vessels,
      and the apical extent was recorded. An autorefractor was used to measure
      refractive error. RESULTS: There were 2481 subjects identified, and 2076 (83.7%)
      participated. The prevalence of pterygium in either eye was 19.6% (95% confidence
      interval (CI) 16.9 to 22.2) and of bilateral pterygium 8.0% (95% CI 7.7 to 8.3).
      Outdoor occupation was an independent predictor of pterygium (p<0.01). The mean
      apical extent from the limbus was 2.2 mm (95% CI 2.05 to 2.35). Higher-grade
      pterygia did not have a significantly greater apical extent (p = 0.35). The
      presence of pterygium was associated with astigmatism, (p = 0.01), and the amount
      of astigmatism increased as both the severity (p<0.01) and apical extent
      increased (p<0.01). Two people of the 84 people blinded in both eyes were
      bilaterally blind from pterygium (1.7%; 95% CI 0.2 to 6.1), and pterygium
      accounted for 2.2% (95% CI 0.7 to 5.0) of blindness in at least one eye. No
      participant had low vision in both eyes due to pterygium, but pterygium led to
      0.8% (95% CI 0.3 to 1.6) of low vision in at least one eye. Pterygium was
      therefore associated with 0.4% (95% CI 0.04 to 1.3) of binocular visual
      impairment and 1.0% (95% CI 0.6 to 1.8) of visual impairment in a least one eye.
      CONCLUSIONS: There is a high prevalence of pterygium in central Myanmar, and the
      risk of developing this condition increases with outdoor occupation. Pterygium in
      this population is associated with considerable visual morbidity, including
      blindness.

PMID- 18055575
TI  - Non-destructive mechanical characterisation of UVA/riboflavin crosslinked
      collagen hydrogels.
AB  - AIMS: To establish a non-destructive method of characterising the mechanical
      properties of collagen hydrogels to model corneal tissue and to examine the
      effect of photochemical crosslinking on their mechanical properties. METHODS:
      Collagen hydrogels were manufactured, submerged in 0.1% riboflavin solution and
      crosslinked using two UVA tube bulbs with an intensity of between 2.8 and 3.2
      mW/cm(2). The hydrogels were clamped around their outer edge and deformed using a
      sphere. The deformation was measured in situ using a long-working-distance
      microscope connected to a CCD camera, and the deformation displacement was used
      with a theoretical model to calculate the Young modulus of the hydrogels.
      Collagen hydrogels seeded with human corneal fibroblasts were used to examine
      cell viability after UVA irradiation. RESULTS: There was an increase in Young
      modulus of the collagen hydrogels after UVA/riboflavin treatment that was
      dependent on the exposure time. UVA irradiation without riboflavin showed
      decreased mechanical integrity and strength. Cell viability was reduced with
      increased UVA exposure time. CONCLUSION: The non-destructive technique
      demonstrated a new methodology comparable with strip extensiometry for cornea or
      corneal model specimens but with more convenient features. This approach could be
      used as an initial step in developing new crosslinking treatments for patients
      with keratoconus.

PMID- 18055577
TI  - Concerns about the long-term outcome of transseptal cardiac resynchronization
      therapy: what we have learned from surgical experience.

PMID- 18055578
TI  - Parathyroid hormone treatment after myocardial infarction promotes cardiac repair
      by enhanced neovascularization and cell survival.
AB  - AIMS: An ongoing concept is that stem cells have the potential to regenerate the
      injured myocardium. In addition to direct vasorelaxing effects on the
      vasculature, which are mediated by an increased cAMP production leading to a
      decreased calcium influx in smooth muscle cells, parathyroid hormone (PTH) was
      recently shown to facilitate stem cell mobilization. Therefore, we analysed in a
      murine model of experimental myocardial infarction (MI) the influence of PTH
      treatment on survival, functional parameters, stem cell migration, and expression
      of vascular endothelial growth factor A (VEGF-A). METHODS AND RESULTS: Mice
      (C57BL/6) were treated with PTH (80 microg/kg/d) for up to 14 days after coronary
      artery ligation. Functional and immunohistochemical analyses were performed at
      days 6 and 30 after MI. Stem cells and VEGF expression in the myocardium were
      analysed by FACS and qRT-PCR at day 2 after MI. PTH-treated animals revealed a
      significant improvement of post-MI survival and myocardial function that was
      related to a subsequent reduction of left ventricular wall thinning and scar
      extension. Infarcted hearts of PTH-treated mice revealed increased numbers of
      CD45(+)/CD34(+) progenitor cells as well as an upregulation of VEGF-A mRNA
      associated with increased neovascularization and cell survival. CONCLUSIONS: PTH
      application after MI increases migration of angiogenic CD45(+)/CD34(+) progenitor
      cells to the ischaemic heart, which may attenuate ischaemic cardiomyopathy. As
      PTH is already used in patients with osteoporosis, our findings may have a direct
      impact on the initiation of clinical studies in patients with ischaemic heart
      disease.

PMID- 18055579
TI  - Sarcomeric dysfunction in heart failure.
AB  - Sarcomeric dysfunction plays a central role in reduced cardiac pump function in
      heart failure. This review focuses on the alterations in sarcomeric proteins in
      diseased myocardium that range from altered isoform expression to post
      translational protein changes such as proteolysis and phosphorylation. Recent
      studies in animal models of heart failure and human failing myocardium converge
      and indicate that sarcomeric dysfunction, including altered maximum force
      development, Ca(2+) sensitivity, and increased passive stiffness, largely
      originates from altered protein phosphorylation, caused by neurohumoral-induced
      alterations in the kinase-phosphatase balance inside the cardiomyocytes. Novel
      therapies, which specifically target phosphorylation sites within sarcomeric
      proteins or the kinases and phosphatases involved, might improve cardiac function
      in heart failure.

PMID- 18055580
TI  - What is the excess risk of infertility in women after genital chlamydia
      infection? A systematic review of the evidence.
AB  - OBJECTIVE: To summarise evidence on the attributable risk of infertility after
      chlamydial infection in women. METHODS: Twelve databases were searched, limited
      to peer-reviewed literature published from January 1970 to September 2007.
      Conference abstracts and reference lists from reviews published since 2000 and
      from key articles were hand-searched. Studies were selected for review if they
      met the following criteria: (1) the study population comprised women of child
      bearing age (defined as 15-45 years) and incorporated a comparison group of women
      documented as "chlamydia negative"; (2) the study outcomes included either
      infertility or successful pregnancy; and (3) the study design was one of the
      following: cohort, randomised controlled trial, "before and after" study,
      screening trial and systematic review. Studies were excluded if they described
      genital infections that either did not include Chlamydia trachomatis or described
      genital chlamydial co-infection, in which no data were available for C
      trachomatis infection alone. RESULTS: 3349 studies were identified by the search.
      One study satisfied the inclusion criteria, a longitudinal investigation
      measuring pregnancy rates in adolescent women with and without current chlamydial
      infection at baseline. That study reported no significant difference in
      subsequent pregnancy rates; however, it had serious methodological limitations,
      which restricted its conclusions. CONCLUSIONS: This systematic review
      demonstrates the absence of valid evidence on the attributable risk of post
      infective tubal factor infertility after genital chlamydial infection. The
      findings contribute empirical data to the growing debate surrounding previous
      assumptions about the natural history of chlamydial infection in women.

PMID- 18055581
TI  - Determinants of consistent condom use among female commercial sex workers in the
      Democratic Republic of Congo: implications for interventions.
AB  - OBJECTIVE: To identify correlates of consistent condom use among commercial sex
      workers (CSW) over a four-week period. METHODS: A total of 2638 CSW selected in
      all the provincial capital cities in the Democratic Republic of Congo using the
      time location sampling technique were interviewed to collect information on
      sociodemographic data, sexual history and behaviour, consumption of intoxicants
      (alcohol and drugs), knowledge of condoms, their accessibility and the pattern of
      their use over a four-week period, and exposure to HIV/AIDS prevention services.
      RESULTS: 40% (95% CI 38.1 to 41.8) of the CSW have used condoms consistently and
      this pattern differed according to the category of sexual partners (61.4% in the
      case of paying partners and 38.2% in the case of non-paying partners). Consistent
      condom use was associated with age, those aged 20-44 years were more likely to be
      consistent users (OR 1.34, 95% CI 1.06 to 1.69), having cited it as a prevention
      means for HIV (OR 2.88, 95% CI 2.09 to 3.96), less time in commercial sex work,
      higher number of clients (OR 3.83, 95% CI 2.95 to 4.96), exposure to voluntary
      counselling and testing (VCT; OR 2.02, 95% CI 1.70 to 2.42), and access to
      condoms (OR 1.51, 95% CI 1.25 to 1.82). CONCLUSIONS: The risk perception bias
      associated with non-paying partners, time as a commercial sex worker and age
      should be taken into account when planning interventions targeting CSW. Access to
      condoms and VCT should be improved because they are likely to impact on
      behaviour.

PMID- 18055582
TI  - Longitudinal effect following initiation of highly active antiretroviral therapy
      on plasma and cervico-vaginal HIV-1 RNA among women in Burkina Faso.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) could decrease HIV-1
      transmissibility by reducing genital and plasma HIV-1 RNA. METHODS: We evaluated
      the effect of HAART on genital and plasma HIV-1 RNA in a cohort of 39
      antiretroviral-naive women in Burkina Faso. Cervico-vaginal lavages were
      collected before HAART initiation and at six visits over 28 weeks while on HAART.
      Blood samples were collected at baseline and at three and four visits for CD4 and
      plasma HIV-1 RNA measurements, respectively. RESULTS: Before HAART, 72% of women
      had detectable genital HIV-1 RNA. After 18 weeks on HAART, only one woman (2.5%)
      had detectable plasma HIV-1 RNA and two women (5.1%) had detectable genital HIV-1
      RNA. Similar results were observed at each follow-up visit. However, 16/34 (47%)
      women with consistently undetectable plasma HIV-1 RNA shed HIV-1 at least once
      between weeks 18 and 28. In samples with detectable genital HIV-1, the mean
      quantity of HIV-1 RNA decreased from 3.87 prior to HAART to 3.04 log(10)
      copies/mL at last visit (median 29 weeks; a 6.8-fold decrease in absolute number
      of copies/mL) (p = 0.04). A significant median CD4 lymphocyte cell gain of 121
      cells/muL (interquartile range 59 to 204) was measured between pre-HAART and last
      visit. CONCLUSION: These findings suggest that HAART could play a role in
      reducing HIV transmission in Africa; however, they underscore the need to
      emphasise safe sex practices with patients taking HAART.

PMID- 18055583
TI  - Pyrroloquinoline quinone is a plant growth promotion factor produced by
      Pseudomonas fluorescens B16.
AB  - Pseudomonas fluorescens B16 is a plant growth-promoting rhizobacterium. To
      determine the factors involved in plant growth promotion by this organism, we
      mutagenized wild-type strain B16 using OmegaKm elements and isolated one mutant,
      K818, which is defective in plant growth promotion, in a rockwool culture system.
      A cosmid clone, pOK40, which complements the mutant K818, was isolated from a
      genomic library of the parent strain. Tn3-gusA mutagenesis of pOK40 revealed that
      the genes responsible for plant growth promotion reside in a 13.3-kb BamHI
      fragment. Analysis of the DNA sequence of the fragment identified 11 putative
      open reading frames, consisting of seven known and four previously unidentified
      pyrroloquinoline quinone (PQQ) biosynthetic genes. All of the pqq genes showed
      expression only in nutrient-limiting conditions in a PqqH-dependent manner.
      Electrospray ionization-mass spectrometry analysis of culture filtrates confirmed
      that wild-type B16 produces PQQ, whereas mutants defective in plant growth
      promotion do not. Application of wild-type B16 on tomato (Solanum lycopersicum)
      plants cultivated in a hydroponic culture system significantly increased the
      height, flower number, fruit number, and total fruit weight, whereas none of the
      strains that did not produce PQQ promoted tomato growth. Furthermore, 5 to 1,000
      nm of synthetic PQQ conferred a significant increase in the fresh weight of
      cucumber (Cucumis sativus) seedlings, confirming that PQQ is a plant growth
      promotion factor. Treatment of cucumber leaf discs with PQQ and wild-type B16
      resulted in the scavenging of reactive oxygen species and hydrogen peroxide,
      suggesting that PQQ acts as an antioxidant in plants.

PMID- 18055584
TI  - Core genome responses involved in acclimation to high temperature.
AB  - Plants can acclimate rapidly to environmental conditions, including high
      temperatures. To identify molecular events important for acquired
      thermotolerance, we compared viability and transcript profiles of Arabidopsis
      thaliana treated to severe heat stress (45 degrees C) without acclimation or
      following two different acclimation treatments. Notably, a gradual increase to 45
      degrees C (22 degrees C to 45 degrees C over 6 h) led to higher survival and to
      more and higher-fold transcript changes than a step-wise acclimation (90 min at
      38 degrees C plus 120 min at 22 degrees C before 45 degrees C). There were
      significant differences in the total spectrum of transcript changes in the two
      treatments, but core components of heat acclimation were apparent in the overlap
      between treatments, emphasizing the importance of performing transcriptome
      analysis in the context of physiological response. In addition to documenting
      increases in transcripts of specific genes involved in processes predicted to be
      required for thermotolerance (i.e. protection of proteins and of translation,
      limiting oxidative stress), we also found decreases in transcripts (i.e. for
      programmed cell death, basic metabolism, and biotic stress responses), which are
      likely equally important for acclimation. Similar protective effects may also be
      achieved differently, such as prevention of proline accumulation, which is toxic
      at elevated temperatures and which was reduced by both acclimation treatments but
      was associated with transcript changes predicted to either reduce proline
      synthesis or increase degradation in the two acclimation treatments. Finally,
      phenotypic analysis of T-DNA insertion mutants of genes identified in this
      analysis defined eight new genes involved in heat acclimation, including
      cytosolic ascorbate peroxidase and the transcription factors HsfA7a (heat shock
      transcription factor A7a) and NF-X1.

PMID- 18055585
TI  - Micro-electrode flux estimation confirms that the Solanum pimpinellifolium cu3
      mutant still responds to systemin.
AB  - In this study, we introduce the Micro-Electrode Ion Flux Estimation technique as
      a sensitive and accurate technique to study systemin-induced changes in ion
      fluxes from isolated nearly intact plant tissues. Our results demonstrate the
      effectiveness and value of the Micro-Electrode Ion Flux Estimation technique to
      monitor and characterize those elicitor-induced ion flux changes from intact
      tissues. We used the method to monitor the systemin-induced changes in ion fluxes
      from leaf tissue of various plant species, including wild-type and cu3 mutant
      tomato (Solanum pimpinellifolium) plants, and confirm previous observations, but
      now in intact leaf tissue. Upon exposure of leaf tissue of plant species from the
      subtribe solaneae to systemin, the H(+) influx and K(+) efflux were transiently
      strongly increased. Plant species of other clades did not show a response upon
      systemin exposure. Although it has been reported that the gene containing the cu3
      null mutation is identical to the SR160/tBRI1 gene, which encodes the
      systemin/brassinosteroid receptor and is essential in systemin and
      brassinosteroid perception, we observed no differences in the response of H(+)
      and K(+) fluxes from both wild-type and mutant leaf tissue to systemin. Also, the
      effects of various pharmacological effectors on systemin-induced flux changes
      were similar. Moreover, a SR160/tBRI1 transgene-containing tobacco (Nicotiana
      tabacum) line was insensitive to systemin, whereas both this line and its wild
      type predecessor were responsive to the elicitor flg22. Our results support the
      conclusion that the Cu3 receptor of tomato is not the systemin receptor, and,
      hence, another receptor is the principal systemin receptor.

PMID- 18055586
TI  - Characterization of the PHO1 gene family and the responses to phosphate
      deficiency of Physcomitrella patens.
AB  - PHO1 was previously identified in Arabidopsis (Arabidopsis thaliana) as a protein
      involved in loading inorganic phosphate (Pi) into the xylem of roots and its
      expression was associated with the vascular cylinder. Seven genes homologous to
      AtPHO1 (PpPHO1;1-PpPHO1;7) have been identified in the moss Physcomitrella
      patens. The corresponding proteins harbor an SPX tripartite domain in the N
      terminal hydrophilic portion and an EXS domain in the conserved C-terminal
      hydrophobic portion, both common features of the plant PHO1 family. Northern-blot
      analysis showed distinct expression patterns for the PpPHO1 genes, both at the
      tissue level and in response to phosphate deficiency. Transgenic P. patens
      expressing the beta-glucuronidase reporter gene under three different PpPHO1
      promoters revealed distinct expression profiles in various tissues. Expression of
      PpPHO1;1 and PpPHO1;7 was specifically induced by Pi starvation. P. patens
      homologs to the Arabidopsis PHT1, DGD2, SQD1, and APS1 genes also responded to Pi
      deficiency by increased mRNA levels. Morphological changes associated with Pi
      deficiency included elongation of caulonemata with inhibition of the formation of
      side branches, resulting in colonies with greater diameter, but reduced mass
      compared to Pi-sufficient plants. Under Pi-deficient conditions, P. patens also
      increased the synthesis of ribonucleases and of an acid phosphatase, and
      increased the ratio of sulfolipids over phospholipids. These results indicate
      that P. patens and higher plants share some common strategies to adapt to Pi
      deficiency, although morphological changes are distinct, and that the PHO1
      proteins are well conserved in bryophyte despite the lack of a developed vascular
      system.

PMID- 18055587
TI  - UV-B signaling pathways with different fluence-rate response profiles are
      distinguished in mature Arabidopsis leaf tissue by requirement for UVR8, HY5, and
      HYH.
AB  - UV-B signaling is an important but poorly understood aspect of light
      responsiveness in plants. Arabidopsis (Arabidopsis thaliana) UV RESISTANCE LOCUS8
      (UVR8) is a recently identified UV-B-specific signaling component that regulates
      UV-protective responses. Using the uvr8 mutant, we defined genetically distinct
      UVR8-dependent and UVR8-independent pathways that stimulate different sets of
      genes in mature Arabidopsis leaf tissue. Both pathways operate at 1 micromol m(
      2) s(-1) UV-B and above, but the UVR8-dependent pathway is able to stimulate UV
      protective genes even in response to 0.1 micromol m(-2) s(-1) UV-B. Both pathways
      function in mutants lacking phytochromes, cryptochromes, or phototropins. Genes
      encoding the ELONGATED HYPOCOTYL5 (HY5) and HY5 HOMOLOG (HYH) transcription
      factors are induced at low UV-B fluence rates (0.1 micromol m(-2) s(-1)).
      Experiments with hy5 and hyh mutants reveal that both these factors mediate
      responses of the UVR8-dependent pathway, acting with partial or complete
      redundancy to stimulate expression of particular genes. Furthermore, evidence is
      presented that all UVR8 pathway genes are likely to be regulated by HY5/HYH and
      that these transcription factors do not mediate UV-B responses independent of
      UVR8. Finally, we highlight the functions of HY5 and HYH in UV protection and
      show that HY5 plays the more critical role. This research provides evidence that,
      in UV-B signaling, UVR8, HY5, and HYH act together in a photoregulatory pathway
      and demonstrates a new role for HYH in UV-B responses.

PMID- 18055588
TI  - Metabolomics reveals novel pathways and differential mechanistic and elicitor
      specific responses in phenylpropanoid and isoflavonoid biosynthesis in Medicago
      truncatula cell cultures.
AB  - High-performance liquid chromatography coupled to ultraviolet photodiode array
      detection and ion-trap mass spectrometry was used to analyze the intra- and
      extracellular secondary product metabolome of Medicago truncatula cell suspension
      cultures responding to yeast elicitor (YE) or methyl jasmonate (MeJA). Data
      analysis revealed three phases of intracellular response to YE: a transient
      response in mainly (iso)flavonoid metabolites such as formononetin and biochanin
      A that peaked at 12 to 18 h following elicitation and then declined; a sustained
      response through 48 h for compounds such as medicarpin and daidzin; and a lesser
      delayed and protracted response starting at 24 h postelicitation, e.g. genistein
      diglucoside. In contrast, most compounds excreted to the culture medium reached
      maximum levels at 6 to 12 h postelicitation and returned to basal levels by 24 h.
      The response to MeJA differed significantly from that to YE. Although both
      resulted in accumulation of the phytoalexin medicarpin, coordinated increases in
      isoflavonoid precursors were only observed for YE and not MeJA-treated cells.
      However, MeJA treatment resulted in a correlated decline in isoflavone
      glucosides, and did not induce the secretion of metabolites into the culture
      medium. Three novel methylated isoflavones, 7-hydroxy-6,4'-dimethoxyisoflavone
      (afrormosin), 6-hydroxy-7,4'-dimethoxyisoflavone (alfalone), and 5,7-dihydroxy
      4',6-dimethoxy isoflavone (irisolidone), were induced by YE, and labeling studies
      indicated that the first two were derived from formononetin. Our results
      highlight the metabolic flexibility within the isoflavonoid pathway, suggest new
      pathways for complex isoflavonoid metabolism, and indicate differential
      mechanisms for medicarpin biosynthesis depending on the nature of elicitation.

PMID- 18055589
TI  - Cytoplasmic calcium increases in response to changes in the gravity vector in
      hypocotyls and petioles of Arabidopsis seedlings.
AB  - Plants respond to a large variety of environmental signals, including changes in
      the gravity vector (gravistimulation). In Arabidopsis (Arabidopsis thaliana)
      seedlings, gravistimulation is known to increase the cytoplasmic free calcium
      concentration ([Ca(2+)](c)). However, organs responsible for the [Ca(2+)](c)
      increase and the underlying cellular/molecular mechanisms remain to be solved. In
      this study, using Arabidopsis seedlings expressing apoaequorin, a Ca(2+)
      sensitive luminescent protein in combination with an ultrasensitive photon
      counting camera, we clarified the organs where [Ca(2+)](c) increases in response
      to gravistimulation and characterized the physiological and pharmacological
      properties of the [Ca(2+)](c) increase. When the seedlings were gravistimulated
      by turning 180 degrees, they showed a transient biphasic [Ca(2+)](c) increase in
      their hypocotyls and petioles. The second peak of the [Ca(2+)](c) increase
      depended on the angle but not the speed of rotation, whereas the initial peak
      showed diametrically opposite characters. This suggests that the second
      [Ca(2+)](c) increase is specific for changes in the gravity vector. The potential
      mechanosensitive Ca(2+)-permeable channel (MSCC) inhibitors Gd(3+) and La(3+),
      the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
      (BAPTA), and the endomembrane Ca(2+)-permeable channel inhibitor ruthenium red
      suppressed the second [Ca(2+)](c) increase, suggesting that it arises from Ca(2+)
      influx via putative MSCCs in the plasma membrane and Ca(2+) release from
      intracellular Ca(2+) stores. Moreover, the second [Ca(2+)](c) increase was
      attenuated by actin-disrupting drugs cytochalasin B and latrunculin B but not by
      microtubule-disrupting drugs oryzalin and nocodazole, implying that actin
      filaments are partially involved in the hypothetical activation of Ca(2+)
      permeable channels. These results suggest that the second [Ca(2+)](c) increase
      via MSCCs is a gravity response in the hypocotyl and petiole of Arabidopsis
      seedlings.

PMID- 18055590
TI  - Identification of two catalases in Azotobacter vinelandii: a KatG homologue and a
      novel bacterial cytochrome c catalase, CCCAv.
AB  - Azotobacter vinelandii produces two detectable catalases during growth on minimal
      medium. The heat-labile catalase expressed during exponential growth phase was
      identified as a KatG homologue by liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) using a mixed protein sample. The second catalase was heat resistant
      and had substantial residual activity after treatment at 90 degrees C. This
      enzyme was purified by anion-exchange and size exclusion chromatography and was
      found to exhibit strong absorption at 407 nm, which is often indicative of
      associated heme moieties. The purified protein was fragmented by proteinase K and
      identified by LC-MS/MS. Some identity was shared with the MauG/bacterial
      cytochrome c peroxidase (BCCP) protein family, but the enzyme exhibited a strong
      catalase activity never before observed in this family. Because two putative c
      type heme sites (CXXCH) were predicted in the peptide sequence and were
      demonstrated experimentally, the enzyme was designated a cytochrome c catalase
      (CCC(Av)). However, the local organization of the CCC(Av) heme motifs differed
      significantly from that of the BCCPs as the sites were confined to the C-terminal
      half of the catalase. A possible Ca2+ binding motif, previously described in the
      BCCPs, is also present in the CCC(Av) peptide sequence. Some instability in the
      presence of EGTA was observed. Expression of the catalase was abolished in cccA
      mutants, resulting in a nearly 8,700-fold reduction in peroxide resistance in
      stationary phase.

PMID- 18055591
TI  - Roles of the major, small, acid-soluble spore proteins and spore-specific and
      universal DNA repair mechanisms in resistance of Bacillus subtilis spores to
      ionizing radiation from X rays and high-energy charged-particle bombardment.
AB  - The role of DNA repair by nonhomologous end joining (NHEJ), homologous
      recombination, spore photoproduct lyase, and DNA polymerase I and genome
      protection via alpha/beta-type small, acid-soluble spore proteins (SASP) in
      Bacillus subtilis spore resistance to accelerated heavy ions (high-energy charged
      [HZE] particles) and X rays has been studied. Spores deficient in NHEJ and
      alpha/beta-type SASP were significantly more sensitive to HZE particle
      bombardment and X-ray irradiation than were the recA, polA, and splB mutant and
      wild-type spores, indicating that NHEJ provides an efficient DNA double-strand
      break repair pathway during spore germination and that the loss of the alpha/beta
      type SASP leads to a significant radiosensitivity to ionizing radiation,
      suggesting the essential function of these spore proteins as protectants of spore
      DNA against ionizing radiation.

PMID- 18055592
TI  - Genetic and functional properties of the self-transmissible Yersinia
      enterocolitica plasmid pYE854, which mobilizes the virulence plasmid pYV.
AB  - Yersinia strains frequently harbor plasmids, of which the virulence plasmid pYV,
      indigenous in pathogenic strains, has been thoroughly characterized during the
      last decades. Yet, it has been unknown whether the nonconjugative pYV can be
      transferred by helper plasmids naturally occurring in this genus. We have
      isolated the conjugative plasmids pYE854 (95.5 kb) and pYE966 (70 kb) from a
      nonpathogenic and a pathogenic Yersinia enterocolitica strain, respectively, and
      demonstrate that both plasmids are able to mobilize pYV. The complete sequence of
      pYE854 has been determined. The transfer proteins and oriT of the plasmid reveal
      similarities to the F factor. However, the pYE854 replicon does not belong to the
      IncF group and is more closely related to a plasmid of gram-positive bacteria.
      Plasmid pYE966 is very similar to pYE854 but lacks two DNA regions of the larger
      plasmid that are dispensable for conjugation.

PMID- 18055593
TI  - Reduced apo-fumarate nitrate reductase regulator (apoFNR) as the major form of
      FNR in aerobically growing Escherichia coli.
AB  - Under anoxic conditions, the Escherichia coli oxygen sensor FNR (fumarate nitrate
      reductase regulator) is in the active state and contains a [4Fe-4S] cluster.
      Oxygen converts [4Fe-4S]FNR to inactive [2Fe-2S]FNR. After prolonged exposure to
      air in vitro, apoFNR lacking a Fe-S cluster is formed. ApoFNR can be
      differentiated from Fe-S-containing forms by the accessibility of the five Cys
      thiol residues, four of which serve as ligands for the Fe-S cluster. The presence
      of apoFNR in aerobically and anaerobically grown E. coli was analyzed in situ
      using thiol reagents. In anaerobically and aerobically grown cells, the membrane
      permeable monobromobimane labeled one to two and four Cys residues, respectively;
      the same labeling pattern was found with impermeable thiol reagents after cell
      permeabilization. Alkylation of FNR in aerobic bacteria and counting the labeled
      residues by mass spectrometry showed a form of FNR with five accessible Cys
      residues, corresponding to apoFNR with all Cys residues in the thiol state.
      Therefore, aerobically growing cells contain apoFNR, whereas a significant amount
      of Fe-S-containing FNR was not detected under these conditions. Exposure of
      anaerobic bacteria to oxygen caused conversion of Fe-S-containing FNR to apoFNR
      within 6 min. ApoFNR from aerobic bacteria contained no disulfide, in contrast to
      apoFNR formed in vitro by air inactivation, and all Cys residues were in the
      thiol form.

PMID- 18055594
TI  - Binding site determinants for the LysR-type transcriptional regulator PcaQ in the
      legume endosymbiont Sinorhizobium meliloti.
AB  - LysR-type transcriptional regulators represent one of the largest groups of
      prokaryotic regulators described to date. In the gram-negative legume
      endosymbiont Sinorhizobium meliloti, enzymes involved in the protocatechuate
      branch of the beta-ketoadipate pathway are encoded within the pcaDCHGB operon,
      which is subject to regulation by the LysR-type protein PcaQ. In this work,
      purified PcaQ was shown to bind strongly (equilibrium dissociation constant, 0.54
      nM) to a region at positions -78 to -45 upstream of the pcaD transcriptional
      start site. Within this region, we defined a PcaQ binding site with dyad symmetry
      that is required for regulation of pcaD expression in vivo and for binding of
      PcaQ in vitro. We also demonstrated that PcaQ participates in negative
      autoregulation by monitoring expression of pcaQ via a transcriptional fusion to
      lacZ. Although pcaQ homologues are present in many alpha-proteobacteria, this
      work describes the first reported purification of this regulator, as well as
      characterization of its binding site, which is conserved in Agrobacterium
      tumefaciens, Rhizobium leguminosarum, Rhizobium etli, and Mesorhizobium loti.

PMID- 18055595
TI  - Evolution of acetoclastic methanogenesis in Methanosarcina via horizontal gene
      transfer from cellulolytic Clostridia.
AB  - Phylogenetic analysis confirmed that two genes required for acetoclastic
      methanogenesis, ackA and pta, were horizontally transferred to the ancestor of
      Methanosarcina from a derived cellulolytic organism in the class Clostridia. This
      event likely occurred within the last 475 million years, causing profound changes
      in planetary methane biogeochemistry.

PMID- 18055596
TI  - Regulation of the yjjQ-bglJ operon, encoding LuxR-type transcription factors, and
      the divergent yjjP gene by H-NS and LeuO.
AB  - The yjjQ and bglJ genes encode LuxR-type transcription factors conserved in
      several enterobacterial species. YjjQ is a potential virulence factor in avian
      pathogenic Escherichia coli. BglJ counteracts the silencing of the bgl (beta
      glucoside) operon by H-NS in E. coli K-12. Here we show that yjjQ and bglJ form
      an operon carried by E. coli K-12, whose expression is repressed by the histone
      like nucleoid structuring (H-NS) protein. The LysR-type transcription factor LeuO
      counteracts this repression. Furthermore, the yjjP gene, encoding a membrane
      protein of unknown function and located upstream in divergent orientation to the
      yjjQ-bglJ operon, is likewise repressed by H-NS. Mapping of the promoters as well
      as the H-NS and LeuO binding sites within the 555-bp intergenic region revealed
      that H-NS binds to the center of the AT-rich regulatory region and distal to the
      divergent promoters. LeuO sites map to the center and to positions distal to the
      yjjQ promoters, while one LeuO binding site overlaps with the divergent yjjP
      promoter. This latter LeuO site is required for full derepression of the yjjQ
      promoters. The arrangement of regulatory sites suggests that LeuO restructures
      the nucleoprotein complex formed by H-NS. Furthermore, the data support the
      conclusion that LeuO, whose expression is likewise repressed by H-NS and which is
      a virulence factor in Salmonella enterica, is a master regulator that among other
      loci, also controls the yjjQ-bglJ operon and thus indirectly the presumptive
      targets of YjjQ and BglJ.

PMID- 18055597
TI  - Galactosyl transferases in mycobacterial cell wall synthesis.
AB  - Two galactosyl transferases can apparently account for the full biosynthesis of
      the cell wall galactan of mycobacteria. Evidence is presented based on enzymatic
      incubations with purified natural and synthetic galactofuranose (Galf) acceptors
      that the recombinant galactofuranosyl transferase, GlfT1, from Mycobacterium
      smegmatis, the Mycobacterium tuberculosis Rv3782 ortholog known to be involved in
      the initial steps of galactan formation, harbors dual beta-(1-->4) and beta-(1-
      >5) Galf transferase activities and that the product of the enzyme, decaprenyl-P
      P-GlcNAc-Rha-Galf-Galf, serves as a direct substrate for full polymerization
      catalyzed by another bifunctional Galf transferase, GlfT2, the Rv3808c enzyme.

PMID- 18055598
TI  - Outer membrane components of the Tad (tight adherence) secreton of
      Aggregatibacter actinomycetemcomitans.
AB  - Prokaryotic secretion relies on proteins that are widely conserved, including
      NTPases and secretins, and on proteins that are system specific. The Tad
      secretion system in Aggregatibacter actinomycetemcomitans is dedicated to the
      assembly and export of Flp pili, which are needed for tight adherence. Consistent
      with predictions that RcpA forms the multimeric outer membrane secretion channel
      (secretin) of the Flp pilus biogenesis apparatus, we observed the RcpA protein in
      multimers that were stable in the presence of detergent and found that rcpA and
      its closely related homologs form a novel and distinct subfamily within a well
      supported gene phylogeny of the entire secretin gene superfamily. We also found
      that rcpA-like genes were always linked to Aggregatibacter rcpB- or Caulobacter
      cpaD-like genes. Using antisera, we determined the localization and gross
      abundances of conserved (RcpA and TadC) and unique (RcpB, RcpC, and TadD) Tad
      proteins. The three Rcp proteins (RcpA, RcpB, and RcpC) and TadD, a putative
      lipoprotein, localized to the bacterial outer membrane. RcpA, RcpC, and TadD were
      also found in the inner membrane, while TadC localized exclusively to the inner
      membrane. The RcpA secretin was necessary for wild-type abundances of RcpB and
      RcpC, and TadC was required for normal levels of all three Rcp proteins. TadC
      abundance defects were observed in rcpA and rcpC mutants. TadD production was
      essential for wild-type RcpA and RcpB abundances, and RcpA did not multimerize or
      localize to the outer membrane without the expression of TadD. These data
      indicate that membrane proteins TadC and TadD may influence the assembly,
      transport, and/or function of individual outer membrane Rcp proteins.

PMID- 18055599
TI  - Identification of type 3 fimbriae in uropathogenic Escherichia coli reveals a
      role in biofilm formation.
AB  - Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial
      infection in the United States. Uropathogenic Escherichia coli (UPEC), the most
      common cause of CAUTI, can form biofilms on indwelling catheters. Here, we
      identify and characterize novel factors that affect biofilm formation by UPEC
      strains that cause CAUTI. Sixty-five CAUTI UPEC isolates were characterized for
      phenotypic markers of urovirulence, including agglutination and biofilm
      formation. One isolate, E. coli MS2027, was uniquely proficient at biofilm growth
      despite the absence of adhesins known to promote this phenotype. Mini-Tn5
      mutagenesis of E. coli MS2027 identified several mutants with altered biofilm
      growth. Mutants containing insertions in genes involved in O antigen synthesis
      (rmlC and manB) and capsule synthesis (kpsM) possessed enhanced biofilm
      phenotypes. Three independent mutants deficient in biofilm growth contained an
      insertion in a gene locus homologous to the type 3 chaperone-usher class fimbrial
      genes of Klebsiella pneumoniae. These type 3 fimbrial genes (mrkABCDF), which
      were located on a conjugative plasmid, were cloned from E. coli MS2027 and could
      complement the biofilm-deficient transconjugants when reintroduced on a plasmid.
      Primers targeting the mrkB chaperone-encoding gene revealed its presence in CAUTI
      strains of Citrobacter koseri, Citrobacter freundii, Klebsiella pneumoniae, and
      Klebsiella oxytoca. All of these mrkB-positive strains caused type 3 fimbria
      specific agglutination of tannic acid-treated red blood cells. This is the first
      description of type 3 fimbriae in E. coli, C. koseri, and C. freundii. Our data
      suggest that type 3 fimbriae may contribute to biofilm formation by different
      gram-negative nosocomial pathogens.

PMID- 18055600
TI  - RpoS expression and the general stress response in Azotobacter vinelandii during
      carbon and nitrogen diauxic shifts.
AB  - The general stress response mediated by the sigma factor RpoS is important for
      survival of bacteria in adverse environments. A mutant unable to produce RpoS was
      constructed using the diazotrophic bacterium Azotobacter vinelandii strain UW.
      Under nondesiccating, solid-medium growth conditions the wild type was culturable
      for 16.5 years, while the rpoS mutant remained viable for only 10 months. The
      rpoS mutant exhibited reduced survival compared to the wild type following
      hydrogen peroxide stress, and stationary phase cells were killed rapidly by 15 mM
      H2O2. Three catalases (Kat1, Kat2, and Kat3) were expressed in the wild type
      under the conditions used. Kat2 was expressed in exponential phase during shake
      flask growth and could be induced under highly aerated conditions in all growth
      phases, suggesting that there was induction by reactive oxygen intermediates.
      Kat3 was possibly an isoform of Kat2. In contrast, Kat1 was expressed in an RpoS
      dependent manner during the mid-exponential to late stationary phases. RpoS
      expression did not occur exclusively in stationary phase but was influenced by
      changes in carbon and nitrogen source availability. There was 26- to 28-fold
      induction of the RpoS protein during acetate-to-glucose and ammonium-to-N2
      diauxic shifts. Following recovery of growth on the alternative carbon or
      nitrogen source, RpoS protein concentrations declined rapidly to a basal level.
      However, rpoS mRNA levels did not correlate directly to RpoS levels, suggesting
      that there was posttranscriptional regulation. Evidence obtained using the RpoS
      dependent reporter Kat1 suggested that there is regulation of the RNAP:RpoS
      holoenzyme at the level of complex formation or activity.

PMID- 18055601
TI  - A highly conserved protein of unknown function is required by Sinorhizobium
      meliloti for symbiosis and environmental stress protection.
AB  - We report here the first characterization of the Sinorhizobium meliloti open
      reading frame SMc01113. The SMc01113 protein is a member of a highly conserved
      protein family, universal among bacteria. We demonstrate that the SMc01113 gene
      is absolutely required for S. meliloti symbiosis with alfalfa and also for the
      protection of the bacterium from a wide range of environmental stresses.

PMID- 18055602
TI  - A feedback regulatory module formed by LITTLE ZIPPER and HD-ZIPIII genes.
AB  - The Arabidopsis thaliana REVOLUTA (REV) protein is a member of the class III
      homeodomain-leucine zipper (HD-ZIPIII) proteins. REV is a potent regulator of
      leaf polarity and vascular development. Here, we report the identification of a
      gene family that encodes small leucine zipper-containing proteins (LITTLE ZIPPER
      [ZPR] proteins) where the leucine zipper is similar to that found in REV,
      PHABULOSA, and PHAVOLUTA proteins. The transcript levels of the ZPR genes
      increase in response to activation of a steroid-inducible REV protein. We show
      that the ZPR proteins interact with REV in vitro and that ZPR3 prevents DNA
      binding by REV in vitro. Overexpression of ZPR proteins in Arabidopsis results in
      phenotypes similar to those seen when HD-ZIPIII function is reduced. We propose a
      negative feedback model in which REV promotes transcription of the ZPR genes. The
      ZPR proteins in turn form heterodimers with the REV protein, preventing it from
      binding DNA. The HD-ZIPIII/ZPR regulatory module would serve not only to dampen
      the effect of fluctuations in HD-ZIPIII protein levels but more importantly would
      provide a potential point of regulation (control over the ratio of inactive
      heterodimers to active homodimers) that could be influenced by other components
      of the pathway governing leaf polarity.

PMID- 18055603
TI  - Cell-fate switch of synergid to egg cell in Arabidopsis eostre mutant embryo sacs
      arises from misexpression of the BEL1-like homeodomain gene BLH1.
AB  - In Arabidopsis thaliana, the female gametophyte is a highly polarized structure
      consisting of four cell types: one egg cell and two synergids, one central cell,
      and three antipodal cells. In this report, we describe the characterization of a
      novel female gametophyte mutant, eostre, which affects establishment of cell
      fates in the mature embryo sac. The eostre phenotype is caused by misexpression
      of the homeodomain gene BEL1-like homeodomain 1 (BLH1) in the embryo sac. It is
      known that BELL-KNAT proteins function as heterodimers whose activities are
      regulated by the Arabidopsis ovate family proteins (OFPs). We show that the
      phenotypic effect of BLH1 overexpression is dependent upon the class II knox gene
      KNAT3, suggesting that KNAT3 must be expressed and functional during
      megagametogenesis. Moreover, disruption of At OFP5, a known interactor of KNAT3
      and BLH1, partially phenocopies the eostre mutation. Our study indicates that
      suppression of ectopic activity of BELL-KNOX TALE complexes, which might be
      mediated by At OFP5, is essential for normal development and cell specification
      in the Arabidopsis embryo sac. As eostre-1 embryo sacs also show nuclear
      migration abnormalities, this study suggests that a positional mechanism might be
      directing establishment of cell fates in early megagametophyte development.

PMID- 18055604
TI  - Photosystem II assembly and repair are differentially localized in Chlamydomonas.
AB  - Many proteins of the photosynthesis complexes are encoded by the genome of the
      chloroplast and synthesized by bacterium-like ribosomes within this organelle. To
      determine where proteins are synthesized for the de novo assembly and repair of
      photosystem II (PSII) in the chloroplast of Chlamydomonas reinhardtii, we used
      fluorescence in situ hybridization, immunofluorescence staining, and confocal
      microscopy. These locations were defined as having colocalized chloroplast mRNAs
      encoding PSII subunits and proteins of the chloroplast translation machinery
      specifically under conditions of PSII subunit synthesis. The results revealed
      that the synthesis of the D1 subunit for the repair of photodamaged PSII
      complexes occurs in regions of the chloroplast with thylakoids, consistent with
      the current model. However, for de novo PSII assembly, PSII subunit synthesis was
      detected in discrete regions near the pyrenoid, termed T zones (for translation
      zones). In two PSII assembly mutants, unassembled D1 subunits and incompletely
      assembled PSII complexes localized around the pyrenoid, where we propose that
      they mark an intermediate compartment of PSII assembly. These results reveal a
      novel chloroplast compartment that houses de novo PSII biogenesis and the
      regulated transport of newly assembled PSII complexes to thylakoid membranes
      throughout the chloroplast.

PMID- 18055605
TI  - BIN4, a novel component of the plant DNA topoisomerase VI complex, is required
      for endoreduplication in Arabidopsis.
AB  - How plant organs grow to reach their final size is an important but largely
      unanswered question. Here, we describe an Arabidopsis thaliana mutant,
      brassinosteroid-insensitive4 (bin4), in which the growth of various organs is
      dramatically reduced. Small organ size in bin4 is primarily caused by reduced
      cell expansion associated with defects in increasing ploidy by endoreduplication.
      Raising nuclear DNA content in bin4 by colchicine-induced polyploidization
      partially rescues the cell and organ size phenotype, indicating that BIN4 is
      directly and specifically required for endoreduplication rather than for
      subsequent cell expansion. BIN4 encodes a plant-specific, DNA binding protein
      that acts as a component of the plant DNA topoisomerase VI complex. Loss of BIN4
      triggers an ATM- and ATR-dependent DNA damage response in postmitotic cells, and
      this response coincides with the upregulation of the cyclin B1;1 gene in the same
      cell types, suggesting a functional link between DNA damage response and
      endocycle control.

PMID- 18055606
TI  - PRR3 Is a vascular regulator of TOC1 stability in the Arabidopsis circadian
      clock.
AB  - The pseudoresponse regulators (PRRs) participate in the progression of the
      circadian clock in Arabidopsis thaliana. The founding member of the family,
      TIMING OF CAB EXPRESSION1 (TOC1), is an essential component of the
      transcriptional network that constitutes the core mechanism of the circadian
      oscillator. Recent data suggest a role in circadian regulation for all five
      members of the PRR family; however, the molecular function of TOC1 or any other
      PRRs remains unknown. In this work, we present evidence for the involvement of
      PRR3 in the regulation of TOC1 protein stability. PRR3 was temporally coexpressed
      with TOC1 under different photoperiods, yet its tissue expression was only
      partially overlapping with that of TOC1, as PRR3 appeared restricted to the
      vasculature. Decreased expression of PRR3 resulted in reduced levels of TOC1
      protein, while overexpression of PRR3 caused an increase in the levels of TOC1,
      all without affecting the amount of TOC1 transcript. PRR3 was able to bind to
      TOC1 in yeast and in plants and to perturb TOC1 interaction with ZEITLUPE (ZTL),
      which targets TOC1 for proteasome-dependent degradation. Together, our results
      indicate that PRR3 might function to modulate TOC1 stability by hindering ZTL
      dependent TOC1 degradation, suggesting the existence of local regulators of clock
      activity and adding to the growing importance of posttranslational regulation in
      the design of circadian timing mechanisms in plants.

PMID- 18055607
TI  - Network inference, analysis, and modeling in systems biology.

PMID- 18055608
TI  - Quantitative proteomics in plants: choices in abundance.

PMID- 18055609
TI  - The central cell plays a critical role in pollen tube guidance in Arabidopsis.
AB  - The sperm cell of flowering plants cannot migrate unaided and must be transported
      by the pollen tube cell of the male gametophyte to achieve successful
      fertilization. Long-distance pollen tube guidance is controlled by the seven
      celled female gametophyte, the embryo sac. Previous reports showed that the
      synergid cell of the embryo sac is essential for pollen tube guidance. Here, we
      report the identification of a central cell guidance (ccg) mutant, which is
      defective in micropylar pollen tube guidance. CCG encodes a nuclear protein with
      an N-terminal conserved zinc beta-ribbon domain that is functionally
      interchangeable with that of TFIIB in yeast. This suggests that CCG might act as
      a transcription regulator for pollen tube guidance. CCG is expressed in the
      central cell of the female gametophyte. Expression of CCG in the central cell
      alone is sufficient to restore the normal pollen tube guidance phenotype,
      demonstrating that the central cell plays a critical role in pollen tube
      guidance.

PMID- 18055610
TI  - VPS9a, the common activator for two distinct types of Rab5 GTPases, is essential
      for the development of Arabidopsis thaliana.
AB  - Rab5, a subfamily of Rab GTPases, regulates a variety of endosomal functions as a
      molecular switch. Arabidopsis thaliana has two different types of Rab5-member
      GTPases: conventional type, ARA7 and RHA1, and a plant-specific type, ARA6. We
      found that only one guanine nucleotide exchange factor (GEF), named VPS9a, can
      activate all Rab5 members to GTP-bound forms in vitro in spite of their diverged
      structures. In the vps9a-1 mutant, whose GEF activity is completely lost,
      embryogenesis was arrested at the torpedo stage. Green fluorescent protein (GFP)
      ARA7 and ARA6-GFP were diffused in cytosol like GDP-fixed mutants of Rab5 in
      vps9a-1, indicating that both types of GTPase are regulated by VPS9a. In the
      leaky vps9a-2 mutant, elongation of the primary root was severely affected.
      Overexpression of the GTP-fixed form of ARA7 suppressed the vps9a-2 mutation, but
      overexpression of ARA6 had no apparent effects. These results indicate that the
      two types of plant Rab5 members are functionally differentiated, even though they
      are regulated by the same activator, VPS9a.

PMID- 18055611
TI  - Synthesis of the D2 protein of photosystem II in Chlamydomonas is controlled by a
      high molecular mass complex containing the RNA stabilization factor Nac2 and the
      translational activator RBP40.
AB  - Gene expression in chloroplasts is regulated mainly at the posttranscriptional
      level. In the green alga Chlamydomonas reinhardtii, synthesis of the D2 protein
      (PsbD), which is the rate-determining subunit for the assembly of photosystem II,
      depends on the RNA stability factor Nac2. In addition, the RNA binding protein
      RBP40 has been implicated in translational control via a U-rich element in the 5'
      untranslated region (5'UTR) of the psbD mRNA. Here, we report the identification
      of the RBP40 gene based on mass spectrometric analysis of its purified product.
      Unexpectedly, this was found to be identical to the previously described RNA
      binding protein RB38, which had been suggested to be involved in the regulation
      of D1 protein synthesis. However, we show that RBP40 binds to the psbD 5'UTR in a
      Nac2-dependent fashion both in vitro and in vivo. Molecular characterization of
      RBP40 RNA interference lines confirmed that RBP40 specifically affects the
      initiation of D2 synthesis. Native polyacrylamide gel electrophoresis,
      coimmunoprecipitation, and sedimentation analyses revealed that Nac2 and RBP40
      form parts of a complex of 550 kD that is displaced from the psbD mRNA prior to
      polysome assembly. Together, these data indicate that the processes of 5'UTR
      mediated RNA stabilization and translation initiation are tightly coupled in
      Chlamydomonas.

PMID- 18055614
TI  - The Journal of Experimental Biology Outstanding Paper Prize, 2007.

PMID- 18055612
TI  - A viroid RNA with a specific structural motif inhibits chloroplast development.
AB  - Peach latent mosaic viroid (PLMVd) is a chloroplast-replicating RNA that
      propagates in its natural host, peach (Prunus persica), as a complex mixture of
      variants, some of which are endowed with specific structural and pathogenic
      properties. This is the case of variant PC-C40, with an insertion of 12 to 13
      nucleotides that folds into a hairpin capped by a U-rich loop, which is
      responsible for an albino-variegated phenotype known as peach calico (PC). We
      have applied a combination of ultrastructural, biochemical, and molecular
      approaches to dissect the pathogenic effects of PC-C40. Albino sectors of leaves
      infected with variant PC-C40 presented palisade cells that did not completely
      differentiate into a columnar layer and altered plastids with irregular shape and
      size and with rudimentary thylakoids, resembling proplastids. Furthermore,
      impaired processing and accumulation of plastid rRNAs and, consequently, of the
      plastid translation machinery was observed in the albino sectors of leaves
      infected with variant PC-C40 but not in the adjacent green areas or in leaves
      infected by mosaic-inducing or latent variants (including PC-C40Delta, in which
      the 12- to 13-nucleotide insertion was deleted). Protein gel blot and RT-PCR
      analyses showed that the altered plastids support the import of nucleus-encoded
      proteins, including a chloroplast RNA polymerase, the transcripts of which were
      detected. RNA gel blot and in situ hybridizations revealed that PLMVd replicates
      in the albino leaf sectors and that it can invade the shoot apical meristem and
      induce alterations in proplastids, bypassing the RNA surveillance system that
      restricts the entry of a nucleus-replicating viroid and most RNA viruses.
      Therefore, a non-protein-coding RNA with a specific structural motif can
      interfere with an early step of the chloroplast developmental program, leading
      ultimately to an albino-variegated phenotype resembling that of certain
      variegated mutants in which plastid rRNA maturation is also impaired. Our results
      highlight the potential of viroids for further dissection of RNA trafficking and
      pathogenesis in plants.

PMID- 18055613
TI  - Lysigenous aerenchyma formation in Arabidopsis is controlled by LESION SIMULATING
      DISEASE1.
AB  - Aerenchyma tissues form gas-conducting tubes that provide roots with oxygen under
      hypoxic conditions. Although aerenchyma have received considerable attention in
      Zea mays, the signaling events and genes controlling aerenchyma induction remain
      elusive. Here, we show that Arabidopsis thaliana hypocotyls form lysigenous
      aerenchyma in response to hypoxia and that this process involves H(2)O(2) and
      ethylene signaling. By studying Arabidopsis mutants that are deregulated for
      excess light acclimation, cell death, and defense responses, we find that the
      formation of lysigenous aerenchyma depends on the plant defense regulators LESION
      SIMULATING DISEASE1 (LSD1), ENHANCED DISEASE SUSCEPIBILITY1 (EDS1), and
      PHYTOALEXIN DEFICIENT4 (PAD4) that operate upstream of ethylene and reactive
      oxygen species production. The obtained results indicate that programmed cell
      death of lysigenous aerenchyma in hypocotyls occurs in a similar but independent
      manner from the foliar programmed cell death. Thus, the induction of aerenchyma
      is subject to a genetic and tissue-specific program. The data lead us to conclude
      that the balanced activities of LSD1, EDS1, and PAD4 regulate lysigenous
      aerenchyma formation in response to hypoxia.

PMID- 18055615
TI  - Mechanical and energetic factors underlying gait transitions in bluegill sunfish
      (Lepomis macrochirus).
AB  - As their swimming speed increased, bluegill sunfish (Lepomis macrochirus)
      switched from pectoral-fin-powered labriform swimming to undulations of the body
      axis. This gait transition occurred at a mean swimming speed of 0.24+/-0.01 m s(
      1) and a pectoral fin beat frequency of 2.79+/-0.11 Hz (mean +/- s.e.m., N=6).
      The power output available from the main upstroke (adductor profundus) and
      downstroke (abductor superficialis) muscles, measured using the work-loop
      technique was maximal at the gait transition point. The cost of transport,
      measured by respirometry, increased as the fish switched from labriform to
      undulatory swimming. Our data show that bluegill changed gait as swimming speed
      increased to recruit additional muscle mass, rather than to maximize economy, as
      is the case for many terrestrial animals.

PMID- 18055616
TI  - Mechanical properties of the rigid and hydrostatic skeletons of molting blue
      crabs, Callinectes sapidus Rathbun.
AB  - Molting in crustaceans involves significant changes in the structure and function
      of the exoskeleton as the old cuticle is shed and a new one is secreted. The
      flimsy new cuticle takes several days to harden and during this time crabs rely
      on a hydrostatic skeletal support system for support and movement. This change
      from a rigid to a hydrostatic skeletal support mechanism implies correlated
      changes in the function, and thus mechanical properties, of the cuticle. In
      particular, it must change from primarily resisting compression, bending and
      torsional forces to resisting tension. This study was designed to explore the
      changes in the mechanical properties of the crustacean cuticle as the animals
      switch between two distinct skeletal support mechanisms. Samples of cuticle were
      removed from blue crabs, Callinectes sapidus, at 1 h (soft-shell stage), 12 h
      (paper-shell stage), and 7 days (hard-shell stage) following molting. We measured
      and compared the flexural stiffness, Young's modulus of elasticity (in tension),
      and tensile strength for each postmolt stage. We found that the hard-shell
      cuticle has a flexural stiffness fully four orders of magnitude greater than the
      soft-shell and paper-shell cuticle. Although the soft-shell cuticle has a Young's
      modulus significantly lower than that of the paper-shell and hard-shell cuticle,
      it has the same tensile strength. Thus, the soft-shell and paper-shell cuticles
      are unable to resist the significant bending forces associated with a rigid
      skeletal support system, but can resist the tensile forces that characterize
      hydrostatic support systems. The mechanical properties of the cuticle thus change
      dramatically during molting in association with the change in function of the
      cuticle. These results emphasize the significant role that mechanics plays in the
      evolution of the molting process in arthropods, and possibly other ecdysozoans.

PMID- 18055617
TI  - Returning on empty: extreme blood O2 depletion underlies dive capacity of emperor
      penguins.
AB  - Blood gas analyses from emperor penguins (Aptenodytes forsteri) at rest, and
      intravascular P(O(2)) profiles from free-diving birds were obtained in order to
      examine hypoxemic tolerance and utilization of the blood O(2) store during dives.
      Analysis of blood samples from penguins at rest revealed arterial P(O(2))s and
      O(2) contents of 68+/-7 mmHg (1 mmHg= 133.3 Pa) and 22.5+/-1.3 ml O(2) dl(-1)
      (N=3) and venous values of 41+/-10 mmHg and 17.4+/-2.9 ml O(2) dl(-1) (N=9).
      Corresponding arterial and venous Hb saturations for a hemoglobin (Hb)
      concentration of 18 g dl(-1) were >91% and 70%, respectively. Analysis of P(O(2))
      profiles obtained from birds equipped with intravascular P(O(2)) electrodes and
      backpack recorders during dives revealed that (1) the decline of the final blood
      P(O(2)) of a dive in relation to dive duration was variable, (2) final venous
      P(O(2)) values spanned a 40-mmHg range at the previously measured aerobic dive
      limit (ADL; dive duration associated with onset of post-dive blood lactate
      accumulation), (3) final arterial, venous and previously measured air sac P(O(2))
      values were indistinguishable in longer dives, and (4) final venous P(O(2))
      values of longer dives were as low as 1-6 mmHg during dives. Although blood O(2)
      is not depleted at the ADL, nearly complete depletion of the blood O(2) store
      occurs in longer dives. This extreme hypoxemic tolerance, which would be
      catastrophic in many birds and mammals, necessitates biochemical and molecular
      adaptations, including a shift in the O(2)-Hb dissociation curve of the emperor
      penguin in comparison to those of most birds. A relatively higher-affinity Hb is
      consistent with blood P(O(2)) values and O(2) contents of penguins at rest.

PMID- 18055618
TI  - Endothelin and endothelin converting enzyme-1 in the fish gill: evolutionary and
      physiological perspectives.
AB  - In euryhaline fishes like the killifish (Fundulus heteroclitus) that experience
      daily fluctuations in environmental salinity, endothelin 1 (EDN1) may be an
      important regulator molecule necessary to maintain ion homeostasis. The purpose
      of this study was to determine if EDN1 and the endothelin converting enzyme
      (ECE1; the enzyme necessary for cleaving the precursor proendothelin-1 to EDN1)
      are present in the killifish, to determine if environmental salinity regulates
      their expression, and to examine the phylogenetic relationships among the EDNs
      and among the ECEs. We sequenced killifish gill cDNA for two EDN1 orthologues,
      EDN1A and EDN1B, and also sequenced a portion of ECE1 cDNA. EDN1A and ECE1 mRNA
      are expressed ubiquitously in the killifish while EDN1B mRNA has little
      expression in the killifish opercular epithelium or gill. Using in situ
      hybridization and immunohistochemistry, EDN1 was localized to large round cells
      adjacent to the mitochondrion-rich cells of the killifish gill, and to lamellar
      pillar cells. In the gill, EDN1A and EDN1B mRNA levels did not differ with acute
      (<24 h) or chronic (30 days) acclimation to seawater (SW); however, EDN1B levels
      increased threefold post SW to freshwater (FW) transfer, and ECE1 mRNA levels
      significantly increased twofold over this period. ECE1 mRNA levels also increased
      sixfold over 24 h post FW to SW transfer. Chronic exposure to SW or FW had little
      effect on ECE1 mRNA levels. Based upon our cellular localization studies, we
      modeled EDN1 expression in the fish gill and conclude that it is positioned to
      act as a paracrine regulator of gill functions in euryhaline fishes. It also may
      function as an autocrine on pillar cells, where it is hypothesized to regulate
      local blood flow in the lamellae. From our phylogenetic analyses, ECE is
      predicted to have an ancient origin and may be a generalist endoprotease in non
      vertebrate organisms, while EDNs are vertebrate-specific peptides and may be key
      characters in vertebrate evolution.

PMID- 18055619
TI  - Parasites, proteomics and performance: effects of gregarine gut parasites on
      dragonfly flight muscle composition and function.
AB  - In previous work, we found that dragonflies infected with gregarine gut parasites
      have reduced muscle power output, loss of lipid oxidation in their flight
      muscles, and a suite of symptoms similar to mammalian metabolic syndrome. Here,
      we test the hypothesis that changes in muscle protein composition underlie the
      observed changes in contractile performance. We found that gregarine infection
      was associated with a 10-fold average reduction in abundance of a approximately
      155 kDa fragment of muscle myosin heavy chain (MHC; approximately 206 kDa intact
      size). Insect MHC gene sequences contain evolutionarily conserved amino acid
      motifs predicted for calpain cleavage, and we found that calpain digestion of
      purified dragonfly MHC produced a peptide of approximately 155 kDa. Thus, gut
      parasites in dragonflies are associated with what appears to be a reduction in
      proteolytic degradation of MHC. MHC155 abundance showed a strong negative
      relationship to muscle power output in healthy dragonflies but either no
      relationship or a weakly positive relationship in infected dragonflies. Troponin
      T (TnT) protein isoform profiles were not significantly different between healthy
      and infected dragonflies but whereas TnT isoform profile was correlated with
      power output in healthy dragonflies, there was no such correlation in infected
      dragonflies. Multivariate analyses of power output based on MHC155 abundance and
      a principal component of TnT protein isoform abundances explained 98% of the
      variation in muscle power output in healthy dragonflies but only 29% when data
      from healthy and infected dragonflies were pooled. These results indicate that
      important, yet largely unexplored, functional relationships exist between
      (pathways regulating) myofibrillar protein expression and (post-translational)
      protein processing. Moreover, infection by protozoan parasites of the midgut is
      associated with changes in muscle protein composition (i.e. across body
      compartments) that, either alone or in combination with other unmeasured changes,
      alter muscle contractile performance.

PMID- 18055620
TI  - Holdfast heroics: comparing the molecular and mechanical properties of Mytilus
      californianus byssal threads.
AB  - The marine mussel Mytilus californianus Conrad inhabits the most wave-exposed
      regions of the rocky intertidal by dint of its extraordinary tenacity. Tenacity
      is mediated in large part by the byssus, a fibrous holdfast structure. M.
      californianus byssal threads, which are mechanically superior to the byssal
      threads of other mytilids, are composed almost entirely of a consortium of three
      modular proteins known as the preCols. In this study, the complete primary
      sequence of preCols from M. californianus was deduced and compared to that of two
      related species with mechanically inferior byssal threads, M. edulis Linnaeus and
      M. galloprovincialis Lamarck in order to explore structure-function
      relationships. The preCols from M. californianus are more divergent from the
      other two species than they are from one another. However, the degree of
      divergence is not uniform among the various domains of the preCols, allowing us
      to speculate on their mechanical role. For instance, the extra spider silk-like
      runs of alanine-rich sequence in the flanking domains of M. californianus may
      increase crystalline order, enhancing strength and stiffness. Histidine-rich
      domains at the termini, in contrast, are highly conserved between species,
      suggesting a mechanical role common to all three. Mechanical testing of pH
      treated and chemically derivatized distal threads strongly suggests that
      histidine side chains are ligands in reversible, metal-mediated cross-links in
      situ. By combining the mechanical and sequence data, yield and self-healing in
      the distal region of threads have been modeled to emphasize the intricate
      interplay of enthalpic and entropic effects during tensile load and recovery.

PMID- 18055621
TI  - Turning behaviour depends on frictional damping in the fruit fly Drosophila.
AB  - Turning behaviour in the fruit fly Drosophila depends on several factors
      including not only feedback from sensory organs and muscular control of wing
      motion, but also the mass moments of inertia and the frictional damping
      coefficient of the rotating body. In the present study we evaluate the
      significance of body friction for yaw turning and thus the limits of visually
      mediated flight control in Drosophila, by scoring tethered flies flying in a
      flight simulator on their ability to visually compensate a bias on a moving
      object and a visual background panorama at different simulated frictional
      dampings. We estimated the fly's natural damping coefficient from a numerical
      aerodynamic model based on both friction on the body and the flapping wings
      during saccadic turning. The model predicts a coefficient of 54 x 10(-12) Nm s,
      which is more than 100-times larger than the value estimated from a previous
      study on the body alone. Our estimate suggests that friction plays a larger role
      for yaw turning in Drosophila than moments of inertia. The simulator experiments
      showed that visual performance of the fruit fly collapses near the physical
      conditions estimated for freely flying animals, which is consistent with the
      suggested role of the halteres for flight stabilization. However, kinematic
      analyses indicate that the measured loss of flight control might be due
      predominantly to the limited fine control in the fly's steering muscles below a
      threshold of 1-2 degrees stroke amplitude, rather than resulting from the limits
      of visual motion detection by the fly's compound eyes. We discuss the impact of
      these results and suggest that the elevated frictional coefficient permits freely
      flying fruit flies to passively terminate rotational body movements without
      producing counter-torque during the second half of the saccadic turning
      manoeuvre.

PMID- 18055622
TI  - Structure, ratios and patterns of release in the sex pheromone of an aphid,
      Dysaphis plantaginea.
AB  - Insect communication is primarily via chemicals. In Aphidinae aphids, the
      structure and ratio of iridoid (monoterpenoid) chemicals are known to be
      important components of the sex pheromone. However, for enhanced species
      specificity, it has been suggested that release of sex pheromone might be
      restricted to a narrow time period within the diel cycle. Here, we determine the
      structure, ratios and release patterns of iridoid chemicals produced by a serious
      global pest, the rosy apple aphid, Dysaphis plantaginea. Volatiles were collected
      from batches of oviparae (sexual females) and chemicals identified by gas
      chromatography, mass-spectrometry and microscale NMR spectroscopy.
      (1R,4aS,7S,7aR)-Nepetalactol and (4aS,7S,7aR)-nepetalactone were detected in a
      3.7:1 ratio. To investigate timing of release, we constructed a sequential
      sampling device that allowed volatile chemicals to be captured hourly from 95
      same-aged oviparae over 20 consecutive days. Release patterns of the two sex
      pheromone components show that D. plantaginea oviparae release high levels of the
      two components during photophase and low levels during scotophase. Release of the
      two components increased significantly during the first 3 h of photophase and
      thereafter remained at a high level until the onset of scotophase. The ratio of
      (1R,4aS,7S,7aR)-nepetalactol to (4aS,7S,7aR)-nepetalactone released did not
      change significantly between days two to 14 of the adult stadium, but from the
      15th day onward there was a significant decrease in the relative amount of
      (1R,4aS,7S,7aR)-nepetalactol. Pheromone release was greatest on the eighth day of
      the adult stadium, with up to 8.4 ng of pheromone released per ovipara per hour.
      This is the first report on the full structural identification and ratios of
      volatile iridoid components collected from D. plantaginea oviparae and is also
      the most detailed temporal study on sex pheromone release from any aphid species.
      The lack of a temporally narrow and distinct period of very high sex pheromone
      release suggests that alternative mechanisms or factors for species recognition
      and isolation may be important. Findings are discussed broadly in relation to the
      biology of the aphid.

PMID- 18055623
TI  - Energy availability influences microclimate selection of hibernating bats.
AB  - Many species hibernate to conserve energy during periods of low food and water
      availability. It has long been assumed that the optimal hibernation strategy
      involves long, deep bouts of torpor that minimize energy expenditure. However,
      hibernation has ecological (e.g. decreased predator avoidance) and physiological
      (e.g. sleep deprivation) costs that must be balanced with energy savings;
      therefore, individuals possessing sufficient energy reserves may reduce their use
      of deep torpor. We tested the hypothesis that energy (fat) availability
      influences temperature selection of two fat-storing bat species during
      hibernation. We predicted that individuals with small energy reserves would
      select colder temperatures for hibernation in order to minimize energy
      expenditure, while individuals with larger energy reserves would choose warmer
      temperatures to minimize the costs of hibernation. Results from our field
      experiment indicate that little brown myotis (Myotis lucifugus) hibernating in
      warm microclimates were significantly heavier than individuals hibernating in
      cooler microclimates. To determine if energy availability was mediating this
      relationship, we limited fatty acid availability with mercaptoacetate (MA) and
      quantified its effect on torpid metabolic rate (TMR) and thermal preference of
      big brown bats (Eptesicus fuscus). Administration of MA caused a 43% drop in TMR
      at 10 degrees C and caused bats to choose significantly colder temperatures for
      hibernation. Our results suggest that fat-storing bats minimize torpor expression
      using both physiological and behavioral mechanisms.

PMID- 18055624
TI  - Phenotypic plasticity in female naked mole-rats after removal from reproductive
      suppression.
AB  - Naked mole-rats are fossorial African rodents that live in large, eusocial
      groups. Adult subordinate female mole-rats are reproductively suppressed by the
      dominant breeding female in their colonies. As a result, subordinate females
      remain reproductively quiescent for their entire lives unless they are removed
      from the suppressive presence of the dominant female. This makes subordinate
      female mole-rats a tractable model for studying phenotypic plasticity. We
      measured skeletal growth of subordinate, suppressed females as they changed
      reproductive status. After housing subordinate female mole-rats separately from
      their home colonies, these animals experienced a growth surge that dramatically
      increased their body mass and length. After removal from reproductive
      suppression, females showed an 82% increase in body mass and a 37% increase in
      the length of their lumbar spines. The lumbar vertebrae were the only skeletal
      structures that exhibited this puberty-like growth. After colony separation, body
      mass and lumbar vertebrae growth rates peaked and remained elevated for several
      weeks before returning to control levels--suggestive of a puberty-like 'growth
      spurt'. Although previous studies have characterized pregnancy-induced lumbar
      spine elongation in female mole-rats, we demonstrate a significant change in the
      body morphology of female mole-rats after removal from reproductive suppression
      but before the first pregnancy.

PMID- 18055625
TI  - Strategies for regulation of hemolymph pH in acidic and alkaline water by the
      larval mosquito Aedes aegypti (L.) (Diptera; Culicidae).
AB  - The responses of larval Aedes aegypti to media of pH 4, 7 and 11 provide evidence
      for pH regulatory strategies. Drinking rates in pH 4 media were elevated 3- to 5
      fold above those observed in pH 7 or 11. Total body water was elevated during
      acute exposure to acidic media. During chronic exposure, total body water was
      decreased and Malpighian tubule mitochondrial luminosity, quantified using
      Mitotracker Green FM, increased. Malpighian tubule secretion rates and energy
      demands thus appear to increase dramatically during acid exposure. In alkaline
      media, drinking rates were quite low. Larvae in pH 11 media excreted net acid
      (0.12 nequiv H(+) g(-1) h(-1)) and the pH indicators azolitmin and bromothymol
      blue revealed that the rectal lumen is acidic in vivo at all ambient pH values.
      The anal papillae (AP) were found to be highly permeant to acid-base equivalents.
      Ambient pH influenced the length, and the mass-specific length, of the AP in the
      presence of NaCl (59.9 mmol l(-1)). In contrast, the length and mass-specific
      length of AP were not influenced by ambient pH in low NaCl conditions.
      Mitochondrial luminosity was reduced in AP of larvae reared in acidic media, and
      was not elevated in alkaline media, relative to that of larvae reared in neutral
      media. These data suggest that the AP may compromise acid-base balance in acidic
      media, and may also be an important site of trade-offs between H(+) homeostasis
      and NaCl uptake in dilute, acidic media.

PMID- 18055626
TI  - Physiological, morphological and behavioural effects of selecting zebra finches
      for divergent levels of corticosterone.
AB  - The effects of environmental stress on the physiology and behaviour of higher
      vertebrates has become an important avenue of research in recent years. Evidence
      from recent studies has suggested that the avian stress-related hormone
      corticosterone (CORT) may play a role in immunocompetence and sexual selection.
      We tested whether CORT is immunosuppressive by studying humoral and cell-mediated
      immune responses in populations of captive zebra finches selected for divergent
      peak levels of CORT. We also investigated whether selection for peak CORT has an
      effect on the quality of several sexually selected regions of the male zebra
      finch; in addition we compared morphometric parameters and the dominance ranking
      in males from the different selection lines. We also tested whether different
      components of the immune system compete for limited resources. We found that
      selection for divergent levels of peak CORT had little effect on humoral
      immunity, male sexual signal quality or dominance ranking. However, contrary to
      expectations, we did find a positive relationship between CORT titre and cell
      mediated immunity, as well as a greater cell-mediated response in the birds
      selected for high CORT titre than those selected for low CORT titre. Consistent
      with predictions, significant negative relationships were found between both
      testosterone and CORT titre on humoral immunity. Birds from the low CORT lines
      were significantly larger in terms of skeletal size than those from the high CORT
      lines. Overall, our results suggest that the cell-mediated immune response is
      associated with a reduction in the humoral response, but only in males, and that
      there is no simple relationship between peak CORT levels and immune function.

PMID- 18055627
TI  - Routine turning maneuvers of koi carp Cyprinus carpio koi: effects of turning
      rate on kinematics and hydrodynamics.
AB  - Spontaneous swimming behaviors of koi carp Cyprinus carpio koi were recorded
      using a video tracking system. Routine single-beat turns were selected from the
      recorded image sequences for kinematic and hydrodynamic analysis. As with C
      starts, the turns can be divided into two stages (stage 1 and stage 2), based on
      kinematics. Stage 1 involves a bend to one side forming a C-shaped curve in the
      body, while stage 2 corresponds to the return flip of the body and tail. The
      turning angle in stage 1 accounts for the greatest portion of the total turning
      angle and the mean turning rate in stage 1 reflects the intensity of turn. The
      effects of the turning rate in stage 1 on both kinematics and hydrodynamics were
      examined. The duration of stage 1 remained relatively stable over a nearly
      tenfold change in turning rate. Consequently, the turning angle is dominated by
      the turning rate in stage 1. The turning radius is not related to the swimming
      speed. Moreover, except in very fast turns, the turning radius is also not
      affected by the turning rate. The angle between the side jet and the carp's
      initial orientation of a turn does not change substantially with the turning
      rate, and it is always close to 90 degrees (94.2+/-3.1 degrees , N=41), so the
      orientation of the side jet in the forthcoming turn can be predicted. The angle
      between the jet and the line joining the center of mass of the carp and the
      trailing edge of the tail (mean value in stage 1) is also always close to 90
      degrees (95.3+/-1.3 degrees , N=41). It is helpful for the carp to maximize the
      torque so as to improve the turning efficiency. In stage 1, the impulsive moment
      obtained from the beat of the body and tail and the mean angular momentum of the
      carp show an agreement in magnitude. Two types of flow patterns in the wake of
      routine single-beat turns are revealed. The difference between the two types of
      wakes is in whether or not a vortex ring and a thrust jet are generated in stage
      2. The recoil speed of the tail, the bending amplitude of the turn, and the angle
      of attack of the tail are three probable factors influencing the flow patterns in
      stage 2.

PMID- 18055629
TI  - Octopamine partially restores walking in hypokinetic cockroaches stung by the
      parasitoid wasp Ampulex compressa.
AB  - When stung by the parasitoid wasp Ampulex compressa, cockroaches Periplaneta
      americana enter a hypokinetic state that is characterized by little, if any,
      spontaneous locomotor activity. In the present study we investigate the effect of
      an octopamine receptor agonist and an antagonist on the locomotor behavior of
      stung and control cockroaches. We show that in cockroaches stung by a wasp the
      octopamine receptor agonist chlordimeform induces a significant increase in
      spontaneous walking. In good agreement, in control individuals an octopamine
      receptor antagonist significantly reduces walking activity. Adipokinetic hormone
      I (AKH-I) promotes spontaneous walking in controls but does not do so in stung
      individuals, which suggests that the venom effect is most probably not mediated
      by AKH-I. Dopamine receptor agonists or antagonists had no significant effect on
      the spontaneous walking of stung or control cockroaches, respectively. The effect
      of the octopamine receptor agonist was maximal when injected into the brain,
      suggesting that the wasp venom interferes with octopaminergic modulation of
      walking initiation in central structures of the cockroach brain.

PMID- 18055628
TI  - Unphosphorylated twitchin forms a complex with actin and myosin that may
      contribute to tension maintenance in catch.
AB  - Molluscan smooth muscle can maintain tension over extended periods with little
      energy expenditure, a process termed catch. Catch is thought to be regulated by
      phosphorylation of a thick filament protein, twitchin, and involves two
      phosphorylation sites, D1 and D2, close to the N and C termini, respectively.
      This study was initiated to investigate the role of the D2 site and its
      phosphorylation in the catch mechanism. A peptide was constructed containing the
      D2 site and flanking immunoglobulin (Ig) motifs. It was shown that the
      dephosphorylated peptide, but not the phosphorylated form, bound to both actin
      and myosin. The binding site on actin was within the sequence L10 to P29. This
      region also binds to loop 2 of the myosin head. The dephosphorylated peptide
      linked myosin and F-actin and formed a trimeric complex. Electron microscopy
      revealed that twitchin is distributed on the surface of the thick filament with
      an axial periodicity of 36.25 nm and it is suggested that the D2 site aligns with
      the myosin heads. It is proposed that the complex formed with the
      dephosphorylated D2 site of twitchin, F-actin and myosin represents a component
      of the mechanical linkage in catch.

PMID- 18055630
TI  - Effects of independently altering body weight and body mass on the metabolic cost
      of running.
AB  - The metabolic cost of running is substantial, despite the savings from elastic
      energy storage and return. Previous studies suggest that generating vertical
      force to support body weight and horizontal forces to brake and propel body mass
      are the major determinants of the metabolic cost of running. In the present
      study, we investigated how independently altering body weight and body mass
      affects the metabolic cost of running. Based on previous studies, we hypothesized
      that reducing body weight would decrease metabolic rate proportionally, and
      adding mass and weight would increase metabolic rate proportionally. Further,
      because previous studies show that adding mass alone does not affect the forces
      generated on the ground, we hypothesized that adding mass alone would have no
      substantial effect on metabolic rate. We manipulated the body weight and body
      mass of 10 recreational human runners and measured their metabolic rates while
      they ran at 3 m s(-1). We reduced weight using a harness system, increased mass
      and weight using lead worn about the waist, and increased mass alone using a
      combination of weight support and added load. We found that net metabolic rate
      decreased in less than direct proportion to reduced body weight, increased in
      slightly more than direct proportion to added load (added mass and weight), and
      was not substantially different from normal running with added mass alone. Adding
      mass alone was not an effective method for determining the metabolic cost
      attributable to braking/propelling body mass. Runners loaded with mass alone did
      not generate greater vertical or horizontal impulses and their metabolic costs
      did not substantially differ from those of normal running. Our results show that
      generating force to support body weight is the primary determinant of the
      metabolic cost of running. Extrapolating our reduced weight data to zero weight
      suggests that supporting body weight comprises at most 74% of the net cost of
      running. However, 74% is probably an overestimate of the metabolic demand of body
      weight to support itself because in reduced gravity conditions decrements in
      horizontal impulse accompanied decrements in vertical impulse.

PMID- 18055631
TI  - Duration of socialization influences responses to a mirror: responses of dominant
      and subordinate crayfish diverge with time of pairing.
AB  - Reflective surfaces have been shown previously to modify behaviour in socialized
      crayfish. Socializing crayfish by pairing them for two weeks established a
      hierarchy with one dominant and one subordinate crayfish per pair. Dominant
      crayfish exhibited specific behaviours, such as cornering, turning and crossing,
      more frequently in a reflective environment than in a non-reflective environment.
      After 2 weeks of pairing, subordinate crayfish did not respond in this manner
      but, instead, performed more reverse walking in a reflective environment. The
      present study investigated how the length of social pairing affects the response
      to mirrors. Crayfish from a communal tank were paired for 30 min or for 3 days,
      and their activity was videotaped for 20 min in a test aquarium lined with
      mirrors on one half and a non-reflective matte lining on the other half. Crayfish
      housed in the communal tank were used as a comparison group. After 30 min of
      pairing, dominant and subordinate crayfish responded similarly to the reflection,
      showing essentially the same pattern for seven of nine behaviours examined. After
      3 days of pairing, dominant crayfish continued to respond to the reflection in
      essentially the same way, but subordinate crayfish behaved differently, showing
      differences in seven out of nine behaviours. Thus, the pattern of responses of
      dominant and subordinate crayfish to reflection diverged with time of pairing.

PMID- 18055632
TI  - Control of neuronal firing by dynamic parallel fiber feedback: implications for
      electrosensory reafference suppression.
AB  - The cancellation of self-generated components of sensory inputs is a key function
      of sensory feedback pathways. In many systems, cerebellar parallel fiber feedback
      mediates this cancellation through anti-Hebbian plasticity, resulting in the
      generation of a negative image of the reafferent inputs. Parallel fiber feedback
      involves direct excitation and disynaptic inhibition as well as synaptic
      plasticity on multiple time scales. How the dynamics of these processes interact
      with anti-Hebbian plasticity to shape synaptic inputs and provide a cancellation
      mechanism remains unclear. In the present study, we investigated the influence of
      parallel fiber feedback onto pyramidal neurons of the electrosensory lateral line
      lobe (ELL) in weakly electric fish under open loop conditions. We mimicked
      naturalistic parallel fiber inputs in an ELL brain slice by implementing an
      experimentally based model of this synaptic pathway using dynamic clamp. We
      showed that as parallel fiber activity increases, the effective input to ELL
      pyramidal neurons changes from net excitation to net inhibition, resulting in a
      non-monotonic firing response. Using a model neuron, we found that this robust
      non-monotonic response is due to a shift from balanced excitation and inhibition
      at low parallel fiber input rates, to dominant inhibition at high input rates. We
      then showed that this non-monotonic response provides a simple basis for negative
      image generation. Through changes in the mean activation rate of parallel fibers,
      the feedback can switch roles between enhancement and suppression of sensory
      inputs in a manner that is directly determined by the slope of the non-monotonic
      response curve.

PMID- 18055633
TI  - Nitrergic modulation of an oviposition digging rhythm in locusts.
AB  - In locusts, a central pattern generator underlies the rhythmic movements of the
      ovipositor valves that serve to drive the abdomen into damp soil in order to lay
      eggs. We have investigated the role of nitric oxide (NO) in the control of this
      oviposition digging rhythm. NO increases the frequency of the rhythm by acting
      via sGC to elevate cGMP, which in turn acts via PKG. Increasing exogenous NO
      levels using the NO donors SNAP and PAPANONOate increased the cycle frequency of
      the fictive digging rhythm, as did increasing endogenous NO by bath application
      of the substrate for NOS, l-arginine. On the other hand, application of the NO
      scavenger PTIO decreased the cycle frequency, indicating that NO must normally
      exert a continuous and dynamic role on the central pattern generator underlying
      the oviposition rhythm. Inhibiting the main molecular target of NO, soluble
      guanylate cyclase, with ODQ reduced the cycle frequency of the rhythm, suggesting
      that NO mediated its effects via sGC and cyclic GMP. Further evidence for this
      was produced by bath application of 8-Br-cGMP, which increased the frequency of
      the rhythm. Bath application of the generic protein kinase inhibitor and a
      selective PKG inhibitor, H-7 and KT-5823, respectively, reduced the frequency of
      the rhythm, suggesting that PKG acted as a target for cGMP. Thus, we conclude
      that NO plays a key role in regulating the frequency of the central pattern
      generator controlling rhythmic egg-laying movements in locusts by acting via
      sGC/cGMP-PKG.

PMID- 18055634
TI  - Aerial hawking and landing: approach behaviour in Natterer's bats, Myotis
      nattereri (Kuhl 1818).
AB  - We compared the flight and echolocation behaviour of a vespertilionid bat (Myotis
      nattereri) approaching a large stationary or a small moving target. Bats were
      trained to either land on a landing grid or to catch a moving tethered mealworm.
      When closing in on these two targets, the bats emitted groups of sounds with
      increasing number of signals and decreasing pulse interval and duration. When
      pursuing the mealworm, the approach phase always ended with a terminal group
      consisting of buzz I and buzz II. When landing, the bats emitted either a
      terminal group consisting of buzz I alone, with one or two extra pulses, or a
      group consisting of buzz I and buzz II. In all situations, buzz I ended on
      average between 47-63 ms prior to contact with the target of interest, which is
      approximately the reaction time of bats. Therefore, the information collected in
      buzz II does not guide the bats to the target. The relevant part of the approach
      phase to reach the target ends with buzz I. The basic sound pattern of this part
      is rather similar and independent of whether the bats approach the large
      stationary or the small moving target.

PMID- 18055635
TI  - Metabolic inactivation of the circadian transmitter, pigment dispersing factor
      (PDF), by neprilysin-like peptidases in Drosophila.
AB  - Recent studies have firmly established pigment dispersing factor (PDF), a C
      terminally amidated octodecapeptide, as a key neurotransmitter regulating
      rhythmic circadian locomotory behaviours in adult Drosophila melanogaster. The
      mechanisms by which PDF functions as a circadian peptide transmitter are not
      fully understood, however; in particular, nothing is known about the role of
      extracellular peptidases in terminating PDF signalling at synapses. In this study
      we show that PDF is susceptible to hydrolysis by neprilysin, an endopeptidase
      that is enriched in synaptic membranes of mammals and insects. Neprilysin cleaves
      PDF at the internal Ser7-Leu8 peptide bond to generate PDF1-7 and PDF8-18.
      Neither of these fragments were able to increase intracellular cAMP levels in
      HEK293 cells cotransfected with the Drosophila PDF receptor cDNA and a firefly
      luciferase reporter gene, confirming that such cleavage results in PDF
      inactivation. The Ser7-Leu8 peptide bond was also the principal cleavage site
      when PDF was incubated with membranes prepared from heads of adult Drosophila.
      This endopeptidase activity was inhibited by the neprilysin inhibitors
      phosphoramidon (IC(50,) 0.15 micromol l(-1)) and thiorphan (IC(50,) 1.2 micromol
      l(-1)). We propose that cleavage by a member of the Drosophila neprilysin family
      of endopeptidases is the most likely mechanism for inactivating synaptic PDF and
      that neprilysin might have an important role in regulating PDF signals within
      circadian neural circuits.

PMID- 18055636
TI  - CARE IV Series: state of knowledge, practice, and translation in
      interdisciplinary arthritis research and care.

PMID- 18055637
TI  - Invited commentary.

PMID- 18055638
TI  - Invited commentary.

PMID- 18055639
TI  - Invited commentary.

PMID- 18055641
TI  - Complementary, holistic, and integrative medicine: atopic dermatitis.

PMID- 18055642
TI  - What's new in childhood organ transplantation.

PMID- 18055643
TI  - Index of suspicion.

PMID- 18055645
TI  - Pleural fluid.

PMID- 18055646
TI  - Visual diagnosis: a 5-year-old child who has facial palsy and rash.

PMID- 18055648
TI  - Toxoplasmosis.

PMID- 18055649
TI  - Pasteurella multocida infections.

PMID- 18055650
TI  - Cystitis.

PMID- 18055651
TI  - Expert committee recommendations regarding the prevention, assessment, and
      treatment of child and adolescent overweight and obesity: summary report.
AB  - To revise 1998 recommendations on childhood obesity, an Expert Committee,
      comprised of representatives from 15 professional organizations, appointed
      experienced scientists and clinicians to 3 writing groups to review the
      literature and recommend approaches to prevention, assessment, and treatment.
      Because effective strategies remain poorly defined, the writing groups used both
      available evidence and expert opinion to develop the recommendations. Primary
      care providers should universally assess children for obesity risk to improve
      early identification of elevated BMI, medical risks, and unhealthy eating and
      physical activity habits. Providers can provide obesity prevention messages for
      most children and suggest weight control interventions for those with excess
      weight. The writing groups also recommend changing office systems so that they
      support efforts to address the problem. BMI should be calculated and plotted at
      least annually, and the classification should be integrated with other
      information such as growth pattern, familial obesity, and medical risks to assess
      the child's obesity risk. For prevention, the recommendations include both
      specific eating and physical activity behaviors, which are likely to promote
      maintenance of healthy weight, but also the use of patient-centered counseling
      techniques such as motivational interviewing, which helps families identify their
      own motivation for making change. For assessment, the recommendations include
      methods to screen for current medical conditions and for future risks, and
      methods to assess diet and physical activity behaviors. For treatment, the
      recommendations propose 4 stages of obesity care; the first is brief counseling
      that can be delivered in a health care office, and subsequent stages require more
      time and resources. The appropriateness of higher stages is influenced by a
      patient's age and degree of excess weight. These recommendations recognize the
      importance of social and environmental change to reduce the obesity epidemic but
      also identify ways healthcare providers and health care systems can be part of
      broader efforts.

PMID- 18055652
TI  - Assessment of child and adolescent overweight and obesity.
AB  - Accurate appropriate assessment of overweight and obesity in children and
      adolescents is a critical aspect of contemporary medical care. However,
      physicians and other health care professionals may find this a somewhat thorny
      field to enter. The BMI has become the standard as a reliable indicator of
      overweight and obesity. The BMI is incomplete, however, without consideration of
      the complex behavioral factors that influence obesity. Because of limited time
      and resources, clinicians need to have quick, evidence-based interventions that
      can help patients and their families recognize the importance of reducing
      overweight and obesity and take action. In an era of fast food, computers, and
      DVDs, it is not easy to persuade patients to modify their diets and to become
      more physically active. Because research concerning effective assessment of
      childhood obesity contains many gaps, this report is intended to provide a
      comprehensive approach to assessment and to present the evidence available to
      support key aspects of assessment. The discussion and recommendations are based
      on >300 studies published since 1995, which examined an array of assessment
      tools. With this information, clinicians should find themselves better equipped
      to face the challenges of assessing childhood overweight and obesity accurately.

PMID- 18055653
TI  - Recommendations for prevention of childhood obesity.
AB  - The majority of US youth are of healthy weight, but the majority of US adults are
      overweight or obese. Therefore, a major health challenge for most American
      children and adolescents is obesity prevention-today, and as they age into
      adulthood. In this report, we review the most recent evidence regarding many
      behavioral and practice interventions related to childhood obesity, and we
      present recommendations to health care providers. Because of the importance, we
      also suggest approaches that clinicians can use to encourage obesity prevention
      among children, including specific counseling strategies and practice-based,
      systems-level interventions. In addition, we suggest how clinicians may interact
      with and promote local and state policy initiatives designed to prevent obesity
      in their communities.

PMID- 18055654
TI  - Recommendations for treatment of child and adolescent overweight and obesity.
AB  - In this article, we review evidence about the treatment of obesity that may have
      applications in primary care, community, and tertiary care settings. We examine
      current information about eating behaviors, physical activity behaviors, and
      sedentary behaviors that may affect weight in children and adolescents. We also
      review studies of multidisciplinary behavior-based obesity treatment programs and
      information about more aggressive forms of treatment. The writing group has drawn
      from the available evidence to propose a comprehensive 4-step or staged-care
      approach for weight management that includes the following stages: (1) Prevention
      Plus; (2) structured weight management; (3) comprehensive multidisciplinary
      intervention; and (4) tertiary care intervention. We suggest that providers
      encourage healthy behaviors while using techniques to motivate patients and
      families, and interventions should be tailored to the individual child and
      family. Although more intense treatment stages will generally occur outside the
      typical office setting, offices can implement less intense intervention
      strategies. We not ony address specific patient behavior goals but also encourage
      practices to modify office systems to streamline office-based care and to prepare
      to coordinate with professionals and programs outside the office for more
      intensive interventions.

PMID- 18055655
TI  - Infant botulism: a 30-year experience spanning the introduction of botulism
      immune globulin intravenous in the intensive care unit at Childrens Hospital Los
      Angeles.
AB  - OBJECTIVE: To report a tertiary care hospital's 30-year experience with the
      diagnosis, treatment, and outcome of infant botulism in the PICU before and after
      the availability of Botulism Immune Globulin Intravenous. METHODS: This was a
      retrospective medical chart review of the 67 patients who had received a
      diagnosis of infant botulism and were admitted to the ICU from 1976 to 2005. The
      ages on presentation, length of hospital stay, length of ICU stay, length of
      mechanical ventilation, and type of botulism toxin were recorded and compared for
      patients who had received Botulism Immune Globulin Intravenous and those who had
      not. On the basis of our results, conclusions were drawn regarding the effect of
      Botulism Immune Globulin Intravenous on the morbidity of infant botulism.
      RESULTS: Sixty-seven patients' charts were reviewed; 23 male and 29 female
      patients did not receive Botulism Immune Globulin Intravenous. Of patients who
      did not receive Botulism Immune Globulin Intravenous, the median age at
      presentation was 71 days, median length of hospital stay was 35 days, ICU stay
      was 24 days, and duration of mechanical ventilation was 17 days. A total of 40%
      had type A toxin, and 60% had type B toxin. There was a significant difference
      between patients with toxin types A and B in length of hospital stay but not
      length of ICU stay or mechanical ventilation. Patients with type A toxin were
      significantly older than patients with type B toxin. Fifteen children received
      Botulism Immune Globulin Intravenous. There were statistically significant
      differences in length of hospital stay, length of ICU stay, and length of
      mechanical ventilation between patients who received Botulism Immune Globulin
      Intravenous and those who did not. CONCLUSIONS: The use of Botulism Immune
      Globulin Intravenous significantly decreased the length of ICU stay, length of
      mechanical ventilation, and overall hospital stay in children with infant
      botulism.

PMID- 18055656
TI  - Behaviors associated with fever in children with autism spectrum disorders.
AB  - OBJECTIVE: Clinical case reports have suggested that the behaviors of children
      with autism spectrum disorders may improve with fever. The purpose of this study
      was to investigate the effect of illness on behaviors of children with autism
      spectrum disorders. Understanding the role of fever, if any, may be informative
      regarding causative mechanisms of and treatment opportunities for autism.
      METHODS: We conducted a prospective study of 30 children (aged 2-18 years) with
      autism spectrum disorders during and after an episode of fever. Parent responses
      to the Aberrant Behavior Checklist were collected during fever (body temperature
      > or = 38.0 degrees C/100.4 degrees F), when fever had abated and the child was
      asymptomatic, and when the child had been fever-free for 7 days. Data were
      compared with those collected from parents of 30 age-, gender-, and language
      skills-matched afebrile children with autism spectrum disorders during similar
      time intervals. RESULTS: Fewer aberrant behaviors were recorded for febrile
      patients on the Aberrant Behavior Checklist subscales of irritability,
      hyperactivity, stereotypy, and inappropriate speech compared with control
      subjects. Per expectation, lethargy scores were greater during fevers, and all
      improvements were transient. Data from patients with fever were stratified on
      variables related to illness severity. In the majority of these subgroup
      comparisons, the data suggested that effects from fever persisted in the less
      sick patients as well as in those with more severe illness. CONCLUSIONS: We
      documented behavior change among children with autism spectrum disorders during
      fever. The data suggest that these changes might not be solely the byproduct of
      general effects of sickness on behavior; however, more research is needed to
      prove conclusively fever-specific effects and elucidate their underlying
      biological mechanisms (possibly involving immunologic and neurobiological
      pathways, intracellular signaling, and synaptic plasticity).

PMID- 18055657
TI  - Preventive care for children in low-income families: how well do Medicaid and
      state children's health insurance programs do?
AB  - OBJECTIVE: Child health problems that are caused or exacerbated by health
      behaviors remain a leading cause of medical spending for children. We examined
      receipt of clinician advice by low-income children, comparing children who had
      public insurance with those who had private insurance, as well as with children
      who were uninsured for part or all of the year. METHODS: We used children who
      were aged 3 to 17 and living in families with incomes of <250% of the federal
      poverty level in the Medical Expenditure Panel Survey data from 2001 to 2003 to
      estimate linear probability models on receipt of preventive advice. The main
      outcome measures were receipt of clinician's advice about healthy eating,
      physical activity, the harmful effects of smoking in the home, proper safety
      restraints in a car, and use of a bicycle helmet. We also examined 2 related
      barriers to receiving clinician advice: whether the child had any preventive care
      visits in the past year and whether the child had a usual source of care other
      than a hospital emergency department. RESULTS: Publicly insured children were
      more likely than privately insured, full-year-uninsured children, and part-year
      uninsured children to have had a preventive care visit in the past year, but
      regardless of health insurance group, many children went without preventive care.
      Even conditional on having had a preventive care visit, 48% did not receive
      clinician advice in any of the areas measured, and 41% of the overweight children
      were advised about neither healthy eating nor exercise in the past year.
      CONCLUSIONS: Enrolling more uninsured children in Medicaid and State Children's
      Health Insurance Programs could improve the chances that families receive advice
      about health behaviors and injury prevention; however, nearly half of the
      children who were insured for the entire year did not receive important advice
      from their clinicians.

PMID- 18055658
TI  - Effectiveness of emergency department asthma management strategies on return
      visits in children: a population-based study.
AB  - BACKGROUND: Emergency departments play an important role in the care of children
      with asthma. Emergency department return-visit rates provide a measure of the
      quality of acute asthma care. OBJECTIVE: Our goal was to describe the
      characteristics of children treated in emergency departments for asthma, the
      resources and asthma management strategies used by emergency departments, and
      their effect on return visits within 72 hours. DESIGN, SETTING, AND PATIENTS: We
      used a population-based cohort study that incorporated both comprehensive
      administrative heath and survey data from all 152 emergency departments in
      Ontario, Canada. We studied all 2- to 17-year-old children who had a visit to an
      emergency department for asthma from April 2003 to March 2005. RESULTS: A total
      of 32,996 children (>9% of children with asthma in Ontario) had at least 1 visit
      to an emergency department for the care of asthma, and most of these visits
      (68.5%) were triaged as high acuity. The vast majority (148 of 152 [97%]) of
      emergency departments reported using at least 1 asthma management strategy, and
      74% used 3 or more. The overall return-visit rate was 5.6%. Logistic regression
      models that accounted for the clustering of patients in emergency departments and
      controlled for patient and emergency department characteristics indicated that
      preprinted order sheets and access to a pediatrician for consultation were
      strategies significantly associated with a reduction in return visits. The 11
      (17%) emergency departments that used both of these strategies had return visit
      rates of 4.4% compared with 6.9% in the 95 (63%) that used neither strategy.
      CONCLUSIONS: Emergency departments use a range of strategies to manage asthma in
      children. Preprinted order sheets and access to pediatricians are associated with
      important reductions in return-visit rates, and more emergency departments should
      consider using these strategies.

PMID- 18055659
TI  - Propofol sedation: intensivists' experience with 7304 cases in a children's
      hospital.
AB  - OBJECTIVE: The objective of this study was to determine the safety profile of
      propofol as a deep-sedation agent in a primarily outpatient program consisting of
      pediatric critical care physicians and specifically trained nurses with oversight
      provided by anesthesiology. One hypothesis was investigated: adverse events
      and/or airway interventions are more likely to occur in children with an abnormal
      airway score. METHODS: A 36-month dual-site prospective, observational, clinical
      study was conducted in a single center with interchangeable providers operating
      within the guidelines of a single sedation program. A total of 7304 propofol
      sedations for 4464 unique patients who ranged in age from 1 month to 21 years
      were studied; >97% of the children were >1 year of age. RESULTS: The following
      adverse reactions were identified, and a descriptive statistical analysis of the
      data were performed: mild oxygen desaturation (85%-90%), 1.73%; serious oxygen
      desaturation (<85%), 2.9%; laryngospasm, 0.27%; regurgitation without aspiration,
      0.05%; regurgitation with aspiration, 0.01%; bronchospasm, 0.15%; and
      hypotension, 31.4%. Interventions required included oral airway, 0.96%; nasal
      trumpet, 1.57%; rescue breaths for >1 minute, 0.37%; intubation, 0.03%; volume
      requirement of >40 mL/kg per hour, 0.11%; sedation-induced ward or PICU
      admission, 0.04%; cardiac arrest medications, 0%; and aborted sedation or
      procedure, 0%. We devised an airway score to identify at-risk patients. Patients
      with an abnormal airway score were significantly more likely to: have oxygen
      desaturation (13.1% vs 4.3%); require an oral airway (5.9% vs 0.8%); and require
      a nasal trumpet (13.9% vs 1.2%). CONCLUSIONS: Propofol has an acceptable safety
      profile for deep sedation when used in the context of a program with critical
      care physicians, specifically trained nurses, and anesthesiology oversight. A
      preprocedure airway score can assist in identifying patients who may require
      airway interventions.

PMID- 18055660
TI  - Gender differences in presentation and course of disease in pediatric patients
      with Crohn disease.
AB  - OBJECTIVE: The objective of this study was to determine gender differences in
      pediatric patients with Crohn disease. METHODS: We conducted a retrospective
      cohort study of 989 consecutive pediatric patients (566 boys, 423 girls) who had
      Crohn disease (aged 0 to 17 years at diagnosis) by using the Pediatric IBD
      Consortium Registry. Uniform data were analyzed to compare the presentation and
      course of disease according to gender. RESULTS: Median follow-up time was 2.8
      years. Mean +/- SD age at diagnosis of inflammatory bowel disease (11.5 +/- 3.8
      years) did not differ by gender. Compared with boys, girls had a higher
      prevalence of mouth sores at symptom onset and a higher prevalence of
      hypoalbuminemia at the time of diagnosis. Location of disease did not differ by
      gender. A higher proportion of girls had abnormal anti-outer membrane porin of
      Escherichia coli levels compared with boys. Girls were at increased risk for
      erythema nodosum/pyoderma gangrenosum and decreased risk for growth failure
      compared with boys. CONCLUSIONS: Girls appear to have an overall more severe
      course of disease; however, boys are at increased risk for developing growth
      failure. Disease course and the impact of disease severity on growth according to
      gender in pediatric Crohn disease require prospective study.

PMID- 18055661
TI  - Fasting nonesterified fatty acid profiles in childhood and their relationship
      with adiposity, insulin sensitivity, and lipid levels.
AB  - OBJECTIVE: The objective of this study was to examine the major constituent of
      nonesterified fatty acids in children with respect to auxologic parameters,
      insulin sensitivity, and lipid levels, because nonesterified fatty acid levels
      are elevated in obesity and are important in the development of comorbidities.
      METHODS: Fasting blood samples were obtained from 73 children (43 girls; 49
      obese; median [range] age: 11.4 [0.9-17.6] years). Concentrations of the major
      circulating nonesterified fatty acids (myristate, palmitate, oleate, stearate,
      and arachidate) were determined by gas chromatography mass spectrometry,
      alongside measurement of insulin, adiponectin, and lipid profiles. RESULTS: The
      sum of all nonesterified fatty acids was significantly higher in obese versus
      normal-weight children, although gender (but not age or puberty) was an important
      determinant, with the difference remaining significant only in boys. Overall,
      obese children had higher concentrations of myristate, palmitate, and oleate but
      not stearate or arachidate. Age was an important determinant of myristate and
      arachidate, whereas gender proved more important for palmitate and stearate.
      Fasting insulin concentrations were not associated with either total
      nonesterified fatty acid concentrations or any of the individual nonesterified
      fatty acids, although a positive correlation was found between adiponectin and
      total nonesterified fatty acid concentrations that was independent of obesity
      status and that seemed mediated by changes in palmitate and stearate. Serum total
      cholesterol and low-density lipoprotein (but not high-density lipoprotein) levels
      seemed to correlate positively with circulating concentrations of palmitate,
      oleate, and stearate, whereas serum triacylglycerols correlated with myristate,
      palmitate, and oleate concentrations. CONCLUSIONS: Nonesterified fatty acid
      concentrations are elevated in obese children, primarily as a result of increases
      in myristate, palmitate, and oleate. Independent effects of nonesterified fatty
      acids on circulating adiponectin levels and lipid parameters were observed,
      although we found no relationship between nonesterified fatty acid concentrations
      and the insulin resistance identified with obesity.

PMID- 18055662
TI  - Predicting language at 2 years of age: a prospective community study.
AB  - OBJECTIVE: This article responds to evidence gaps regarding language impairment
      identified by the US Preventive Services Task Force in 2006. We examine the
      contributions of putative child, family, and environmental risk factors to
      language outcomes at 24 months of age. METHODS: A community-ascertained sample of
      1720 infants who were recruited at 8 months of age were followed at ages 12 and
      24 months in a prospective, longitudinal study in metropolitan Melbourne,
      Australia. Outcomes at 24 months were parent-reported infant communication
      (Communication and Symbolic Behavior Scales and MacArthur-Bates Communicative
      Development Inventories vocabulary production score). Putative risk factors were
      gender, preterm birth, birth weight, multiple birth, birth order, socioeconomic
      status, maternal mental health, maternal vocabulary and education, maternal age
      at birth of child, non-English-speaking background, and family history of speech
      language difficulties. Linear regression models were fitted to total standardized
      Communication and Symbolic Behavior Scales and Communicative Development
      Inventories vocabulary production scores; a logistic regression model was fitted
      to late-talking status at 24 months. RESULTS: The regression models accounted for
      4.3% and 7.0% of the variation in the 24-month Communication and Symbolic
      Behavior Scales and Communicative Development Inventories scores, respectively.
      Male gender and family history were strongly associated with poorer outcomes on
      both instruments. Lower Communication and Symbolic Behavior Scales scores were
      also associated with lower maternal vocabulary and older maternal age. Lower
      vocabulary production scores were associated with birth order and non-English
      speaking background. When the 12-month Communication and Symbolic Behavior Scales
      Total score was added as a covariate in the linear regression of 24-month
      Communication and Symbolic Behavior Scales Total score, it was by far the
      strongest predictor. CONCLUSIONS: These early risk factors explained no more than
      7% of the variation in language at 24 months. They seem unlikely to be helpful in
      screening for early language delay.

PMID- 18055663
TI  - Weight loss in overweight Mexican American children: a randomized, controlled
      trial.
AB  - OBJECTIVES: Childhood overweight has increased significantly in the past 20
      years, with the highest rates noted among Mexican Americans. Although this
      minority group is in significant need of intervention, few programs have
      demonstrated actual decreases in weight. In this study we evaluated an intensive
      healthy lifestyle program designed to result in weight reduction for overweight
      Mexican American children. We hypothesized that children randomly assigned to an
      intensive intervention would significantly reduce their standardized BMI when
      compared with children randomly assigned to a self-help condition. PATIENTS AND
      METHODS: A total of 60 children (33 boys; 55%) between the ages of 10 and 14
      years at or above the 85th percentile for BMI were randomly assigned to a 6-month
      intensive-intervention or self-help condition. RESULTS: Children in the intensive
      intervention condition significantly reduced their standardized BMI when compared
      with the children in the self-help condition. The change in standardized BMI was
      significantly different at both 3 and 6 months, with intensive-intervention
      participants showing greater decreases in weight. CONCLUSIONS: Overall, the
      results were promising, suggesting that an intensive, individualized intervention
      may be an effective means for promoting weight loss in overweight Mexican
      American children.

PMID- 18055664
TI  - Pediatric emergency department visits for diarrheal illness increased after
      release of undertreated sewage.
AB  - CONTEXT: Contamination of local waterways may occur through release of partially
      treated sewage. The Environmental Protection Agency has recently reviewed
      regulatory standards for this practice. However, the health effects of these
      events have not been well studied. OBJECTIVE: Our goal was to identify any
      increase in visits to a pediatric emergency department for diarrheal illness
      after sewage bypass into Lake Michigan. METHODS: The study was conducted as a
      retrospective, observational time-series analysis in a tertiary care children's
      hospital emergency department with an annual volume of approximately 45,000
      visits. We collected data for 2002-2004 pertaining to the daily number of
      emergency department visits for children (aged <19 years) for diarrheal illness
      (using specified International Classification of Diseases, Ninth Edition codes as
      a reference). Daily diarrheal illness visits were the dependent variable in a
      time-series model. The primary independent variable was the occurrence of a
      sewage-bypass event in the 3 to 7 preceding days. Potential confounders included
      the season and daily rainfall. Separate models were created for visits from
      people living in zip codes that used Lake Michigan drinking water and those who
      used other water sources. RESULTS: Over the 3-year study period, there was a mean
      of 5.0 +/- 3.8 (SD) daily visits for diarrheal illness from people who lived in
      zip codes that used Lake Michigan drinking water and 1.2 +/- 1.4 (SD) from
      outside that area. There were 6 sewage-bypass events identified. After adjusting
      for the season and rainfall, there was a significant increase of 2.5 to 2.7
      visits only from people who lived in zip codes that used Lake Michigan drinking
      water after the 2 largest of the 6 bypass events. CONCLUSIONS: Emergency
      department visits for diarrheal illness increased significantly after 2 events of
      release of partially treated sewage into area waterways. These data suggest a
      potentially harmful effect of such practices.

PMID- 18055665
TI  - Influence of institutionalization on time to HIV disease progression in a cohort
      of Romanian children and teens.
AB  - OBJECTIVES: The purpose of this work was to investigate the effect of
      institutionalization on death and CD4 decline in a cohort of 325 HIV-infected
      Romanian children. METHODS: A retrospective database analysis was conducted. Data
      from a nearly 3-year period were examined with Kaplan-Meier survival analysis and
      Cox regression analysis models. Subjects all received primary and HIV specialty
      care and treatment at the Romanian American Children's Center in Constanta,
      Romania. Children in one group resided with their biological families and the
      other children resided in "family home"-style institutions. RESULTS: There was no
      difference between groups for death during the follow-up period, although there
      was a trend for survival advantage for children in institutional care. There was
      no statistically significant difference between the study groups in terms of CD4
      decline, although there was a trend toward greater decline among children who
      resided with their biological families. Children with their biological families
      were more likely to experience disease progression through either death or CD4
      decline than were children in institutions. CONCLUSIONS: The family home-style
      institution may prove to be a replicable model for the safe and appropriate care
      of HIV-infected orphaned and abandoned children and teens.

PMID- 18055666
TI  - Cardiac safety of central nervous system stimulants in children and adolescents
      with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVES: Case reports have raised concerns about the risk of cardiac events
      associated with central nervous system stimulants for the treatment of attention
      deficit/hyperactivity disorder. PATIENTS AND METHODS: This was a retrospective
      cohort study that used 10 years (July 1994 to June 2004) of Florida Medicaid
      claims data cross-linked to Vital Statistics Death Registry data. The cohort was
      composed of all youth 3 to 20 years old who were newly diagnosed with attention
      deficit/hyperactivity disorder. Each month of follow-up was classified according
      to stimulant claims (methylphenidate, amphetamines, and pemoline) as current use
      (active stimulant claim), former use (time after periods of current use), or
      nonuse (time preceding the first stimulant claim, including follow-up of youth
      who were never exposed to stimulants). The study's end points were (1) cardiac
      death, (2) first hospital admission for cardiac causes or (3) first emergency
      department visit for cardiac causes. Risks were compared with time-dependent Cox
      regression analysis adjusting for various cardiac risk factors. RESULTS: During
      124,932 person-years of observation (n = 55,383), 73 youth died, 5 because of
      cardiac causes. No cardiac death occurred during 42,612 person-years of stimulant
      use. Hospital admissions for cardiac cause occurred for 27 children (8 during
      stimulant use, 11 during 35,671 person-years of former use, and 8 during 46,649
      person-years of nonuse); and 1091 children visited the emergency department for
      cardiac causes (8.7 per 1000 person-years). Current stimulant use was associated
      with a 20% increase in the hazard for emergency department visits when compared
      with nonuse. No increased risk was found for periods of former use when compared
      with nonuse. CONCLUSIONS: Incidence rates of cardiac events requiring
      hospitalization were small and similar to national background rates. Stimulants
      were associated with an increase in cardiac emergency department visits. More
      evidence is needed that addresses the long-term risk/benefit of the various
      treatment options and the effect of other cardiac risk factors and comedications.

PMID- 18055667
TI  - Preschooler obesity and parenting styles of mothers and fathers: Australian
      national population study.
AB  - OBJECTIVE: The purpose of this work was to determine relationships between BMI
      status at ages 4 to 5 years and mothers' and fathers' parenting dimensions and
      parenting styles. PARTICIPANTS AND METHODS: Participants were composed of all
      4983 of the 4- to 5-year-old children in wave 1 of the nationally representative
      Longitudinal Study of Australian Children with complete BMI and maternal
      parenting data. Mothers and fathers self-reported their parenting behaviors on 3
      multi-item continuous scales (warmth, control, and irritability) and were each
      categorized as having 1 of 4 parenting styles (authoritative, authoritarian,
      permissive, and disengaged) using internal warmth and control tertile cut points.
      Using a proportional odds model, odds ratios for children being in a higher BMI
      category were computed for mothers and fathers separately and together, after
      adjustment for factors associated with child BMI, including mothers' and fathers'
      BMI status. RESULTS: The sample was composed of 2537 boys and 2446 girls with a
      mean age 56.9 months; 15% were overweight and 5% were obese (International
      Obesity Task Force criteria). Mothers' parenting behaviors and styles were not
      associated in any model with higher odds of children being in a heavier BMI
      category, with or without multiple imputation to account for missing maternal BMI
      data. Higher father control scores were associated with lower odds of the child
      being in a higher BMI category. Compared with the reference authoritative style,
      children of fathers with permissive and disengaged parenting styles had higher
      odds of being in a higher BMI category. CONCLUSIONS: This article is the first,
      to our knowledge, to examine the parenting of both parents in relation to
      preschoolers' BMI status while also adjusting for parental BMI status. Fathers'
      but not mothers' parenting behaviors and styles were associated with increased
      risks of preschooler overweight and obesity. Longitudinal impacts of parenting on
      BMI gain remain to be determined.

PMID- 18055668
TI  - To what extent do educational interventions impact medical trainees' attitudes
      and behaviors regarding industry-trainee and industry-physician relationships?
AB  - BACKGROUND: Recently, academic medical centers have been asked to take the lead
      in voluntarily instituting more stringent regulations regarding pharmaceutical
      industry interactions not only with physicians but also with medical trainees.
      OBJECTIVE: Our goal was to summarize the recent literature regarding the impact
      of educational interventions and regulatory policies on trainee perceptions of
      pharmaceutical industry interactions and/or pharmaceutical industry-related
      trainee behavior. METHODS: We searched Medline and the bibliographies of review
      articles for relevant studies. Articles published before the Accreditation
      Council for Continuing Medical Education standards for commercial support of
      continuing medical education were issued in 1991 were excluded. Two reviewers
      selected empiric studies that (1) reported empiric data about educational
      interventions that were meant to shape trainee knowledge, attitudes, or practices
      concerning the pharmaceutical industry or (2) evaluated the impact of regulatory
      policies on trainee attitudes or behaviors. RESULTS: From 247 identified
      articles, 12 met the inclusion criteria. In 2 of these studies, the impact of
      regulatory policies on trainee attitudes and/or behaviors was assessed. In the
      remaining 10 studies, the impact of various educational interventions developed
      by training programs or schools to shape trainee knowledge, attitudes, or
      practices concerning the pharmaceutical industry were evaluated. CONCLUSIONS:
      Although modest in size, a body of empirical research exists that might inform
      medical educators. Beyond institutional policy that excludes the pharmaceutical
      industry, the evidence reviewed suggests that well-designed seminars, role
      playing, and focused curricula can affect trainee attitudes and behavior,
      although it is not entirely clear whether these changes are sustainable over the
      long-term.

PMID- 18055669
TI  - Successful use of a primary care practice-specialty collaboration in the care of
      an adolescent with chronic fatigue syndrome.
AB  - We report on the successful collaborative care of an adolescent with chronic
      fatigue syndrome between a primary care pediatrician and an academic chronic
      fatigue syndrome specialist located in different cities. Regular telephone and e
      mail communication and clearly defined patient-care roles allowed for timely
      management of symptoms and marked clinical improvement. We discuss ways to
      improve the collaboration of primary care and subspecialty physicians for
      patients with chronic fatigue syndrome and children with special health care
      needs.

PMID- 18055670
TI  - Diagnosis of HIV-1 infection in children younger than 18 months in the United
      States.
AB  - The objectives of this technical report are to describe methods of diagnosis of
      HIV-1 infection in children younger than 18 months in the United States and to
      review important issues that must be considered by clinicians who care for
      infants and young children born to HIV-1-infected women. Appropriate HIV-1
      diagnostic testing for infants and children younger than 18 months differs from
      that for older children, adolescents, and adults because of passively transferred
      maternal HIV-1 antibodies, which may be detectable in the child's bloodstream
      until 18 months of age. Therefore, routine serologic testing of these infants and
      young children is generally only informative before the age of 18 months if the
      test result is negative. Virologic assays, including HIV-1 DNA or RNA assays,
      represent the gold standard for diagnostic testing of infants and children
      younger than 18 months. With such testing, the diagnosis of HIV-1 infection (as
      well as the presumptive exclusion of HIV-1 infection) can be established within
      the first several weeks of life among nonbreastfed infants. Important factors
      that must be considered when selecting HIV-1 diagnostic assays for pediatric
      patients and when choosing the timing of such assays include the age of the
      child, potential timing of infection of the child, whether the infection status
      of the child's mother is known or unknown, the antiretroviral exposure history of
      the mother and of the child, and characteristics of the virus. If the mother's
      HIV-1 serostatus is unknown, rapid HIV-1 antibody testing of the newborn infant
      to identify HIV-1 exposure is essential so that antiretroviral prophylaxis can be
      initiated within the first 12 hours of life if test results are positive. For HIV
      1-exposed infants (identified by positive maternal test results or positive
      antibody results for the infant shortly after birth), it has been recommended
      that diagnostic testing with HIV-1 DNA or RNA assays be performed within the
      first 14 days of life, at 1 to 2 months of age, and at 3 to 6 months of age. If
      any of these test results are positive, repeat testing is recommended to confirm
      the diagnosis of HIV-1 infection. A diagnosis of HIV-1 infection can be made on
      the basis of 2 positive HIV-1 DNA or RNA assay results. In nonbreastfeeding
      children younger than 18 months with no positive HIV-1 virologic test results,
      presumptive exclusion of HIV-1 infection can be based on 2 negative virologic
      test results (1 obtained at > or = 2 weeks and 1 obtained at > or = 4 weeks of
      age); 1 negative virologic test result obtained at > or = 8 weeks of age; or 1
      negative HIV-1 antibody test result obtained at > or = 6 months of age.
      Alternatively, presumptive exclusion of HIV-1 infection can be based on 1
      positive HIV-1 virologic test with at least 2 subsequent negative virologic test
      results (at least 1 of which is performed at > or = 8 weeks of age) or negative
      HIV-1 antibody test results (at least 1 of which is performed at > or = 6 months
      of age). Definitive exclusion of HIV-1 infection is based on 2 negative virologic
      test results, 1 obtained at > or = 1 month of age and 1 obtained at > or = 4
      months of age, or 2 negative HIV-1 antibody test results from separate specimens
      obtained at > or = 6 months of age. For both presumptive and definitive exclusion
      of infection, the child should have no other laboratory (eg, no positive
      virologic test results) or clinical (eg, no AIDS-defining conditions) evidence of
      HIV-1 infection. Many clinicians confirm the absence of HIV-1 infection with a
      negative HIV-1 antibody assay result at 12 to 18 months of age. For breastfeeding
      infants, a similar testing algorithm can be followed, with timing of testing
      starting from the date of complete cessation of breastfeeding instead of the date
      of birth.

PMID- 18055671
TI  - Pediatric preparedness of US emergency departments: a 2003 survey.
AB  - OBJECTIVES: Our goal was to assess the degree of pediatric preparedness of
      emergency departments in the United States. METHODS: A closed-response survey
      based on the American Academy of Pediatrics/American College of Emergency
      Physicians joint policy statement, "Care of Children in the Emergency Department:
      Guidelines for Preparedness," was mailed to 5144 emergency department medical and
      nursing directors. A weighted preparedness score (scale of 0-100) was calculated
      for each emergency department. RESULTS: A total of 1489 useable surveys (29%)
      were received, with 62% completed by emergency department medical directors.
      Eighty-nine percent of pediatric (age: 0-14 years) emergency department visits
      occur in non-children's hospitals, 26% of visits occur in rural or remote
      facilities, and 75% of responding emergency departments see <7000 children per
      year. The vast majority of visits (89%) occur in emergency department areas
      shared with adult patients; 6% occur in a separate pediatric emergency
      department. Only 6% of emergency departments had all recommended equipment and
      supplies. Emergency departments frequently lacked laryngeal mask airways for
      children (50%) and neonatal or infant equipment. In contrast, recommended
      medications were more uniformly available, as were transfer policies for medical
      or surgical intensive care. Fifty-two percent of emergency departments reported
      having a quality improvement/performance improvement plan for pediatric emergency
      patients, and 59% of respondents were aware of the American Academy of
      Pediatrics/American College of Emergency Physicians guidelines. The median
      pediatric-preparedness score for all emergency departments was 55. Pediatric
      preparedness scores were higher for facilities with higher pediatric volume,
      facilities with physician and nursing coordinators for pediatrics, and facilities
      with respondents who reported awareness of the guidelines. CONCLUSION: Pediatric
      preparedness of hospital emergency departments demonstrates opportunities for
      improvement.

PMID- 18055672
TI  - Parents as information intermediaries between primary care and specialty
      physicians.
AB  - OBJECTIVE: In this study we assessed the views of parents of children referred to
      specialty care and the views of the children's primary care and specialty
      physicians about parents' roles as information intermediaries. METHODS: We
      enrolled 179 patients who were newly referred from primary care pediatricians in
      22 practices to 15 pediatric subspecialists in 5 specialties in a study of
      primary care pediatrician-specialist communication. Parents, primary care
      pediatricians, and specialists completed questionnaires by mail or telephone at
      the first visit and 6 months later. Questions included perceived responsibilities
      of parents as information conduits between primary care pediatricians and
      specialists. Opinions of parents, primary care pediatricians, and specialists
      about parents' roles were compared for the sample as a whole, as well as for
      individual cases. Agreement between parents and providers was assessed.
      Demographic and clinical determinants of parents reporting themselves as
      "comfortable with" or "acting" as primary intermediaries were assessed using
      logistic regression. RESULTS: More parents (44%) than primary care physicians
      (30%) felt comfortable with parents acting as primary communicators between their
      children's physicians; 31% of parents who reported that they were the primary
      communicators felt uncomfortable in that role, and there was no agreement between
      parents and physicians about the role of parents in individual cases. Although no
      demographic characteristics of children or parents were associated with parent
      comfort as the primary communicator, parents of children who saw the same
      specialist more than once during the 6-month period felt more comfortable in this
      role. The presence of a chronic condition was not associated with parent comfort.
      CONCLUSIONS: Although parents report more comfort with their own ability as
      information intermediaries than do their children's physicians, the role in which
      they feel comfortable is highly variable. Physicians should discuss with parents
      the roles they feel comfortable in assuming when specialty referrals are
      initiated.

PMID- 18055673
TI  - Early determinants of fruit and vegetable acceptance.
AB  - OBJECTIVE: Our goal was to evaluate the effects of breastfeeding and dietary
      experiences on acceptance of a fruit and a green vegetable by 4- to 8-month-old
      infants. METHODS: Forty-five infants, 44% of whom were breastfed, were assigned
      randomly to 1 of 2 treatment groups. One group was fed green beans, and the other
      was fed green beans and then peaches at the same time of day for 8 consecutive
      days. Acceptance of both foods, as determined by a variety of measures, was
      assessed before and after the home-exposure period. RESULTS: During the initial
      exposure, infants ate more calories from peaches than from green beans. Breastfed
      infants showed greater liking of peaches, as did their mothers, who ate more
      fruits in general than did mothers who formula fed. Although formula-feeding
      mothers ate more green beans, there was no difference in their infants'
      acceptance of this vegetable. For breastfed and formula-fed infants, repeated
      dietary exposure to green beans, with or without peaches, resulted in greater
      consumption of green beans (56.8 vs 93.6 g). Only infants who experienced green
      beans with peaches displayed fewer facial expressions of distaste during feeding.
      Mothers were apparently unaware of these changes in acceptance. CONCLUSIONS:
      Breastfeeding confers an advantage in initial acceptance of a food, but only if
      mothers eat the food regularly. Once weaned, infants who receive repeated dietary
      exposure to a food eat more of it and may learn to like its flavor. However,
      because infants innately display facial expressions of distaste in response to
      certain flavors, caregivers may hesitate to continue offering these foods.
      Mothers should be encouraged to provide their infants with repeated opportunities
      to taste fruits and vegetables and should focus not only on their infants' facial
      expressions but also on their willingness to continue feeding.

PMID- 18055674
TI  - Stability of antibiotics in portable pumps used for bronchial superinfection:
      guidelines for prescribers.
AB  - OBJECTIVES: The aims of this study were (1) to collect data on the stability of
      antibiotics in portable pumps for the treatment of bronchial superinfection in
      patients with cystic fibrosis and (2) to provide guidelines for prescribers.
      METHODS: The stability over 72 hours, in portable pumps stored at 35 degrees C,
      of piperacillin plus tazobactam, ticarcillin plus clavulanic acid, cefsulodin,
      cefepime, and aztreonam was checked at 3 different concentrations. Stability was
      assessed through visual examination, pH measurements, and direct measurements of
      drug concentrations by using high-performance liquid chromatography. All
      parameters were measured at time 0, time 0 plus 24 hours, and time 0 plus 72
      hours. RESULTS: Degradation rates for penicillin plus beta-lactamase inhibitor
      combinations remained <10% at time 0 plus 24 hours for all drugs, but the rate
      for piperacillin reached 12% for the highest concentration tested. The
      cephalosporins cefepime and cefsulodin had significant respective degradation
      rates of 18% and 28% at time 0 plus 24 hours and 60% and 68.5% at time 0 plus 72
      hours, which were linked to the storage temperature. Aztreonam seemed to be
      stable over 72 hours. CONCLUSIONS: This work provides data on drug stability that
      were lacking, allowing recommendations for physicians to optimize the safety and
      efficacy of antibiotic treatment of patients with cystic fibrosis. Piperacillin
      plus tazobactam and ticarcillin plus clavulanic acid infusions must be limited to
      24 hours, and patients receiving cefepime or cefsulodin must wear a cold pack
      close to the ambulatory drug-delivery device during the infusion.

PMID- 18055675
TI  - Pulmonary artery hypertension in formerly premature infants with bronchopulmonary
      dysplasia: clinical features and outcomes in the surfactant era.
AB  - BACKGROUND: Although abnormal pulmonary vascular structure and function in
      preterm infants with bronchopulmonary dysplasia may predispose infants to
      pulmonary artery hypertension, little is known about the characteristics and
      outcomes of bronchopulmonary dysplasia-associated pulmonary artery hypertension
      in the surfactant era. METHODS: We studied 42 premature infants (< 32 weeks of
      gestation) with bronchopulmonary dysplasia who were diagnosed as having pulmonary
      artery hypertension > or = 2 months after birth, between 1998 and 2006, at a
      median age of 4.8 months. Pulmonary artery hypertension was graded through
      echocardiography for all patients; 13 patients also underwent cardiac
      catheterization. RESULTS: Eighteen (43%) of 42 patients had severe pulmonary
      artery hypertension (systemic or suprasystemic right ventricular pressure). Among
      13 patients who underwent catheterization, the mean pulmonary artery pressure was
      43 +/- 8 mmHg and the pulmonary vascular resistance index was 9.9 +/- 2.8 Wood
      units. In 12 patients, pulmonary artery pressure and pulmonary vascular
      resistance improved with 100% oxygen and 80 ppm inhaled nitric oxide but remained
      elevated. The pulmonary vascular resistance index decreased to 7.9 +/- 3.8 Wood
      units in 100% oxygen and to 6.4 +/- 3.1 Wood units with the addition of nitric
      oxide. Sixteen patients (38%) died during the follow-up period. Estimated
      survival rates were 64% +/- 8% at 6 months and 53% +/- 11% at 2 years after
      diagnosis of pulmonary artery hypertension. In multivariate analyses, severe
      pulmonary artery hypertension and small birth weight for gestational age were
      associated with worse survival rates. Among 26 survivors (median follow-up
      period: 9.8 months), pulmonary artery hypertension was improved, relative to its
      most severe level, in 24 patients (89%). CONCLUSION: Premature infants with
      bronchopulmonary dysplasia and severe pulmonary artery hypertension are at high
      risk of death, particularly during the first 6 months after diagnosis of
      pulmonary artery hypertension.

PMID- 18055676
TI  - Intimate partner violence and health care costs and utilization for children
      living in the home.
AB  - OBJECTIVE: The goal was to determine whether differences in health care costs and
      utilization exist for children whose mothers experienced intimate partner
      violence versus those who did not. METHODS: A longitudinal cohort study was
      performed in an integrated health care delivery organization with 760 children of
      mothers with no history of intimate partner violence and 631 children of mothers
      with a history of intimate partner violence since age 18. Health care utilization
      and costs for children before, during, and after intimate partner violence
      exposure were compared with utilization and costs for children with nonabused
      mothers. RESULTS: Health care utilization and health care costs were higher in
      most categories of care for children of mothers with a history of intimate
      partner violence, with significantly higher values for mental health services,
      primary care visits, primary care costs, and laboratory costs. Children of
      mothers with a history of intimate partner violence that ended before the child
      was born had significantly greater utilization of mental health, primary care,
      specialty care, and pharmacy services than did children of mothers who reported
      no intimate partner violence. Children exposed directly to intimate partner
      violence (after birth) had greater emergency department and primary care use
      during the intimate partner violence and were 3 times as likely to use mental
      health services after the intimate partner violence ended. CONCLUSIONS: Children
      whose mothers experienced intimate partner violence have higher health care
      utilization and costs, even if their mothers' abuse stopped before they were
      born. Screening of women for intimate partner violence should be a routine part
      of their health care, and interventions for both the women and their children are
      likely necessary to minimize the effects of intimate partner violence in the
      family.

PMID- 18055677
TI  - Pediatric myocarditis: emergency department clinical findings and diagnostic
      evaluation.
AB  - OBJECTIVE: The goal was to determine, in children with myocarditis, the frequency
      of various presenting symptoms and the sensitivity of clinical and laboratory
      investigations routinely available in the emergency department. METHODS: We
      performed a retrospective review of all patients < 18 years of age who were
      diagnosed as having myocarditis at our institution between May 2000 and May 2006
      and who initially presented to an emergency department. Patients were categorized
      as having definite myocarditis (positive endomyocardial biopsy results) or
      probable myocarditis (diagnosis assigned by a pediatric cardiologist on the basis
      of history, physical examination, and investigation results in the absence of an
      endomyocardial biopsy or in the presence of negative biopsy results). All
      patients were assigned a predominant category of symptoms at presentation on the
      basis of criteria defined a priori. RESULTS: There were 16 cases of definite
      myocarditis and 15 cases of probable myocarditis. The age distribution was
      nonnormal, with peaks among children < or = 3 years and > or = 16 years of age.
      Of 14 patients who were seen by a physician before being diagnosed with
      myocarditis, 57% were originally diagnosed as having pneumonia or asthma. Thirty
      two percent of patients presented with predominantly respiratory symptoms, 29%
      had cardiac symptoms, and 6% had gastrointestinal symptoms. Although evidence of
      cardiac dysfunction was frequently present in the form of respiratory distress,
      only a minority of children had evidence of hepatomegaly or abnormal cardiac
      examination results. The sensitivities of electrocardiograms and chest
      radiographs as screening tests were 93% and 55%, respectively. Among laboratory
      tests studied, aspartate aminotransferase measurement was the most sensitive
      (sensitivity: 85%). CONCLUSIONS: Children with myocarditis present with symptoms
      that can be mistaken for other types of illnesses; respiratory presentations were
      most common. When clinical suspicion of myocarditis exists, chest radiography
      alone is an insufficient screening test. All children should undergo
      electrocardiography. Aspartate aminotransferase testing may be a useful
      adjunctive investigation.

PMID- 18055678
TI  - Effects of two different doses of amino acid supplementation on growth and blood
      amino acid levels in premature neonates admitted to the neonatal intensive care
      unit: a randomized, controlled trial.
AB  - OBJECTIVES: The goal was to measure the effects of 2 distinct strategies for
      parenteral nutrition on neonatal growth and blood amino acid profiles. METHODS:
      In a multicenter trial (n = 11 sites), we randomly allocated premature (23-29
      weeks and 6 days of gestation) neonates to 1 of 2 approaches to intravenous amino
      acid administration. In one group, amino acid supplementation was started at 1.0
      g/kg per day and advanced by 0.5 g/kg per day to a maximum of 2.5 g/kg per day
      (2.5 g/kg per day group). The other group received amino acids starting at 1.5
      g/kg per day and advancing by 1.0 g/kg per day to a maximum of 3.5 g/kg per day
      (3.5 g/kg per day group). Filter paper blood spots were obtained from each infant
      on the day of random assignment and on days 7 and 28 of age, to monitor blood
      amino acid levels. RESULTS: We enrolled 122 neonates (64 in the 3.5 g/kg per day
      group and 58 in the 2.5 g/kg per day group). There were no differences in
      demographic or baseline characteristics between the 2 treatment groups. There was
      no significant difference in growth by day 28 after birth (median weight gain:
      12.9 and 11.4 g/kg per day for the 3.5 and 2.5 g/kg per day groups,
      respectively), and the incidences of secondary morbidities were similar in the 2
      groups. On day 7, blood levels of several amino acids and the serum urea nitrogen
      level were higher in the 3.5 g/kg per day group, compared with the 2.5 g/kg per
      day group; none of the amino acid levels were lower. CONCLUSIONS: Higher doses of
      amino acid supplementation did not improve neonatal growth and were associated
      with increased blood amino acid and urea nitrogen levels.

PMID- 18055679
TI  - Use of bedside ultrasonography for endotracheal tube placement in pediatric
      patients: a feasibility study.
AB  - OBJECTIVE: The purpose of our study was to evaluate the usefulness of bedside
      ultrasonography in verifying endotracheal tube placement in the pediatric
      population. METHODS: This study consisted of 2 phases. In phase I, subjects were
      examined while intubated and after extubation to determine the presence of the
      endotracheal tube by applying each of 2 ultrasound transducers to the
      cricothyroid membrane. In phase II, pediatric patients were examined in the
      emergency department during intubation or immediately after intubation to
      ascertain proper endotracheal tube placement by using bedside ultrasonography.
      These results were compared with the results obtained with a colorimetric end
      tidal carbon dioxide detector and chest radiographs. RESULTS: Forty-nine and 50
      patients (age: 1 day to 17 years) were recruited in the first and second phases
      of the study, respectively. The endotracheal tube was detected in all 99 patients
      by using bedside ultrasonography. Two views were required to show accurately the
      presence of the endotracheal tube in the trachea. Visualization was obtained in
      all cases, although short necks and cervical collars made the procedure more
      challenging. The sniffing position allowed for the best acquisition of high
      quality images. Our linear transducer provided the best images but, because of
      its size, it was not ideal when space was limited. Therefore, the curvilinear
      transducer was used exclusively for phase II. During phase II, the mean times to
      acquire bedside ultrasonographic images of the endotracheal tube through the
      cricothyroid membrane and to obtain a chest radiograph were 17.1 seconds and 14.0
      minutes, respectively. In 3 cases, bedside ultrasonographic images proved to be
      invaluable when the colorimetric end-tidal carbon dioxide detector yielded false
      negative or equivocal readings. CONCLUSIONS: Bedside ultrasonography can be used
      to accurately and rapidly determine the presence of the endotracheal tube within
      the trachea in pediatric patients.

PMID- 18055680
TI  - Clinical characteristics of peanut-allergic children: recent changes.
AB  - OBJECTIVE: The goal was to determine whether patients seen in a referral clinic
      are experiencing initial allergic reactions to peanuts earlier, compared with a
      similar population profiled at a different medical center 10 years ago, and to
      investigate other changes in clinical characteristics of the patients between the
      2 groups. METHODS: We reviewed the medical charts of peanut-allergic patients
      seen in the Duke University pediatric allergy and immunology clinic between July
      2000 and April 2006. RESULTS: The median ages of first peanut exposure and
      reaction were 14 and 18 months, respectively; the respective ages in a similar
      population profiled between 1995 and 1997 were 22 and 24 months. Within our
      patient group, those born before 2000 were first exposed to peanuts at a median
      age of 19 months and reacted at a median age of 21 months, compared with first
      exposure at 12 months and first reaction at 14 months for those born in or after
      2000. Most patients (68%) demonstrated sensitization or clinical allergy to other
      foods (53% to eggs, 26% to cow's milk, 20% to tree nuts, 11% to fish, 9% to
      shellfish, 7% to soy, 6% to wheat, and 6% to sesame seeds). CONCLUSIONS: In the
      past decade, the ages of first peanut exposure and reaction have declined among
      peanut-allergic children seen in a referral clinic. Egg allergy is very common in
      peanut-allergic patients, and sesame seeds should perhaps be considered one of
      the major food allergens. The decline in the age of first peanut reaction seems
      to be attributable to earlier exposure.

PMID- 18055681
TI  - Expression of the epithelial sodium channel in airway epithelium of newborn
      infants depends on gestational age.
AB  - OBJECTIVE: In the newborn infant, removal of fetal lung liquid from the airways
      depends on ion transport through the airway epithelium. The epithelial sodium
      channel is considered rate limiting for the postnatal clearance of lung liquid,
      but it is unknown whether during the early postnatal period the expression of
      epithelial sodium channel is associated with maturity. Our objective was to study
      the relationship between gestational age and epithelial sodium channel expression
      in airway epithelium. METHODS: In 90 newborn infants (preterm [gestational age <
      37]: n = 29; term [gestational age > or = 37]: n = 61), we measured the
      expression of epithelial sodium channel (reported as attomoles of subunit
      expression normalized to femtomoles of expression of cytokeratin 18) in nasal
      epithelium at 1 to 5 and 22 to 28 hours after birth. RESULTS: At 1 to 5 hours
      postnatally, airway expression of alpha-, beta-, and gamma-subunits of epithelial
      sodium channel was lower in preterm than in term infants. At this time point,
      significant correlations existed between gestational age and airway expression of
      alpha- and beta-epithelial sodium channel. By 22 to 28 hours after birth, only
      the expression of beta-epithelial sodium channel had decreased significantly in
      the preterm infants, whereas the expression of all epithelial sodium channel
      subunits had decreased significantly in the term infants. At this time point, no
      difference in expression of any of the subunits was found between preterm and
      term infants. CONCLUSIONS: Airway expression of epithelial sodium channel at 1 to
      5 hours of age is significantly lower in preterm than in term infants. Low
      postnatal expression of alpha-, beta-, and gamma-epithelial sodium channel
      subunits in the airway epithelium may contribute to the development of
      respiratory distress in the preterm infant.

PMID- 18055682
TI  - A cluster-randomized trial of screening for language delay in toddlers: effects
      on school performance and language development at age 8.
AB  - OBJECTIVE: The goal of this study was to assess the effects of screening and
      early treatment of preschool children for language delay on language development
      and school performance at age 8. METHODS: A cluster-randomized, controlled trial
      and follow-up study of 55 child health centers in 6 geographic regions were
      conducted from January 2002 to September 2005. A total of 9419 children who were
      from the general population and aged 15 months at entry were studied. School type
      end school progress was known for 5406 (57.4%) children. In the intervention
      group, a structured screening instrument was conducted twice (at ages 15/18 and
      24 months), and usual care was applied in the control group. The screening
      instrument consisted of a uniform set of questions for the parents and test
      elements for the child. A positive screen result was followed by
      multidisciplinary assessments at speech and hearing centers and subsequent early
      treatment if needed. Percentages of children who attended a special school,
      repeated a class because of language problems, and scored low on standardized
      language tests, in intention-to-screen analyses, were measured. RESULTS: At age
      8, 2.7% in the intervention group and 3.7% in the control group attended a
      special school, 6.1% vs 4.9% had repeated a grade, 8.8% vs 9.7% had deficient
      oral language performance, 4.7% vs 4.7% had deficient reading, and 2.8% vs 4.2%
      had deficient spelling. CONCLUSIONS: Screening toddlers for language delays
      reduces the number of children who require special education and leads to
      improved language performance at age 8. Nationwide implementation of the
      screening might be recommended.

PMID- 18055683
TI  - Mitochondrial disease: a practical approach for primary care physicians.
AB  - Notorious variability in the presentation of mitochondrial disease in the infant
      and young child complicates its clinical diagnosis. Mitochondrial disease is not
      a single entity but, rather, a heterogeneous group of disorders characterized by
      impaired energy production due to genetically based oxidative phosphorylation
      dysfunction. Together, these disorders constitute the most common neurometabolic
      disease of childhood with an estimated minimal risk of developing mitochondrial
      disease of 1 in 5000. Diagnostic difficulty results from not only the variable
      and often nonspecific presentation of these disorders but also from the absence
      of a reliable biomarker specific for the screening or diagnosis of mitochondrial
      disease. A simplified and standardized approach to facilitate the clinical
      recognition of mitochondrial disease by primary physicians is needed. With this
      article we aimed to improve the clinical recognition of mitochondrial disease by
      primary care providers and empower the generalist to initiate appropriate
      baseline diagnostic testing before determining the need for specialist referral.
      This is particularly important in light of the international shortage of
      metabolism specialists to comprehensively evaluate this large and complex disease
      population. It is hoped that greater familiarity among primary care physicians
      with the protean manifestations of mitochondrial disease will facilitate the
      proper diagnosis and management of this growing cohort of pediatric patients who
      present across all specialties.

PMID- 18055684
TI  - State of the evidence on acute asthma management in children: a critical
      appraisal of systematic reviews.
AB  - OBJECTIVE: Our goal was to evaluate clinical, methodologic, and reporting aspects
      of systematic reviews on the management of acute asthma in children. METHODS: We
      undertook a systematic review of systematic reviews on acute asthma management in
      children. We identified eligible reviews by searching the Cochrane Database of
      Systematic Reviews, the Database of Abstracts of Reviews of Effects, Medline, and
      Embase 1990 to March 2006. Data were extracted on clinical issues, methodologic
      characteristics, and results of the reviews. Methodologic quality was assessed
      with the Overview Quality Assessment Questionnaire and with additional questions
      on heterogeneity. Separate reporting on children in mixed adult-pediatric
      population reviews was assessed. Methodologic quality of systematic reviews
      published in peer-reviewed journals was compared with Cochrane reviews. RESULTS:
      A total of 23 systematic reviews were included: 14 were published in the Cochrane
      Library, and 9 were published in peer-reviewed journals. Eight reviews included
      children only, and 15 were mixed-population reviews. The majority of reviews
      defined the study population as having "acute asthma" without a more precise
      definition, and 16 different health outcomes were reported. The overall quality
      according to the Overview Quality Assessment Questionnaire was good, with
      Cochrane reviews showing minimal flaws and journal reviews showing minor flaws
      (median scores: 7 vs 5). Results on children were reported separately in 8 of 15
      mixed-population reviews. Clinical heterogeneity was explored in only 2 of 23
      reviews, and the methods used to identify and address heterogeneity were diverse.
      CONCLUSIONS: The methodologic quality of both the Cochrane and journal reviews on
      the management of acute asthma in children seems good, with Cochrane reviews
      being more rigorous. However, their usefulness for clinical practice is hampered
      by a lack of clear definitions of included populations, clinically important
      health outcomes, and separate reporting on children in mixed reviews. A major
      threat to these reviews' validity is the insufficient identification and handling
      of heterogeneity.

PMID- 18055685
TI  - An adolescent's refusal of medical treatment: implications of the Abraham Cheerix
      case.

PMID- 18055686
TI  - Cobedding twins and higher-order multiples in a hospital setting.

PMID- 18055687
TI  - Patient safety in the pediatric emergency care setting.
AB  - Patient safety is a priority for all health care professionals, including those
      who work in emergency care. Unique aspects of pediatric care may increase the
      risk of medical error and harm to patients, especially in the emergency care
      setting. Although errors can happen despite the best human efforts, given the
      right set of circumstances, health care professionals must work proactively to
      improve safety in the pediatric emergency care system. Specific recommendations
      to improve pediatric patient safety in the emergency department are provided in
      this policy statement.

PMID- 18055689
TI  - The role of schools in combating illicit substance abuse.
AB  - Disturbingly high levels of illicit drug use remain a problem among American
      teenagers. As the physical, social, and psychological "home away from home" for
      most youth, schools naturally assume a primary role in substance abuse education,
      prevention, and early identification. However, the use of random drug testing on
      students as a component of drug prevention programs requires additional, more
      rigorous scientific evaluation. Widespread implementation should await the result
      of ongoing studies to address the effectiveness of testing and evaluate possible
      inadvertent harm. If drug testing on students is conducted, it should never be
      implemented in isolation. A comprehensive assessment and therapeutic management
      program for the student who tests positive should be in place before any testing
      is performed. Schools have the opportunity to work with parents, health care
      professionals, and community officials to use programs with proven effectiveness,
      to identify students who show behavioral risks for drug-related problems, and to
      make referrals to a student's medical home. When use of an illicit substance is
      detected, schools can foster relationships with established health care experts
      to assist them. A student undergoing individualized intervention for using
      illicit substances merits privacy. This requires that awareness of the student's
      situation be limited to parents, the student's physician, and only those
      designated school health officials with a need to know. For the purposes of this
      statement, alcohol, tobacco, and inhalants are not addressed.

PMID- 18055690
TI  - Recognizing and responding to medical neglect.
AB  - A caregiver may fail to recognize or respond to a child's medical needs for a
      variety of reasons. An effective response by a health care professional to
      medical neglect requires a comprehensive assessment of the child's needs, the
      parents' resources, the parents' efforts to provide for the needs of the child,
      and options for ensuring optimal health for the child. Such an assessment
      requires clear, 2-way communication between the family and the health care
      professional. Physicians should consider the least intrusive options for managing
      cases of medical neglect that ensure the health and safety of the child.

PMID- 18055691
TI  - "Late-preterm" infants: a population at risk.
AB  - Late-preterm infants, defined by birth at 34(0/7) through 36(6/7) weeks'
      gestation, are less physiologically and metabolically mature than term infants.
      Thus, they are at higher risk of morbidity and mortality than term infants. The
      purpose of this report is to define "late preterm," recommend a change in
      terminology from "near term" to "late preterm," present the characteristics of
      late-preterm infants that predispose them to a higher risk of morbidity and
      mortality than term infants, and propose guidelines for the evaluation and
      management of these infants after birth.

PMID- 18055693
TI  - Effectiveness of trimethoprim/sulfamethoxazole for children with chronic active
      otitis media.

PMID- 18055694
TI  - Dr. Lucey, editor of Pediatrics receives two honors.

PMID- 18055695
TI  - Dissecting eIF4E action in tumorigenesis.
AB  - Genetically engineered mouse models are powerful tools for studying cancer genes
      and validating targets for cancer therapy. We previously used a mouse lymphoma
      model to demonstrate that the translation initiation factor eIF4E is a potent
      oncogene in vivo. Using the same model, we now show that the oncogenic activity
      of eIF4E correlates with its ability to activate translation and become
      phosphorylated on Ser 209. Furthermore, constitutively activated MNK1, an eIF4E
      Ser 209 kinase, promotes tumorigenesis in a manner similar to eIF4E, and a
      dominant-negative MNK mutant inhibits the in vivo proliferation of tumor cells
      driven by mutations that deregulate translation. Phosphorylated eIF4E promotes
      tumorigenesis primarily by suppressing apoptosis and, accordingly, the anti
      apoptotic protein Mcl-1 is one target of both phospho-eIF4E and MNK1 that
      contributes to tumor formation. Our results provide insight into how eIF4E
      contributes to tumorigenesis and pinpoint a level of translational control that
      may be suitable for therapeutic intervention.

PMID- 18055697
TI  - Optimal scintigraphic evaluation of a hydronephrotic horseshoe kidney.
AB  - A 25-y-old man with horseshoe kidney was referred for diuretic-augmented renal
      scintigraphy. Single-detector dynamic posterior imaging was performed and
      revealed asymmetric retention of radiotracer in the left collecting system. Renal
      scintigraphy was repeated with a modified protocol. Dynamic imaging was performed
      this time using dual-detector acquisition of both anterior and posterior data.
      Thereafter, pregravity and subsequently postgravity static images were obtained
      in both anterior and posterior projections. This second study showed near
      complete emptying of the left collecting system. This case illustrates the
      utility of using simultaneous anterior and posterior imaging and geometric mean
      calculations for functional analysis and also highlights the value of physiologic
      maneuvers to augment the traditional diuretic challenge.

PMID- 18055696
TI  - Motif module map reveals enforcement of aging by continual NF-kappaB activity.
AB  - Aging is characterized by specific alterations in gene expression, but their
      underlying mechanisms and functional consequences are not well understood. Here
      we develop a systematic approach to identify combinatorial cis-regulatory motifs
      that drive age-dependent gene expression across different tissues and organisms.
      Integrated analysis of 365 microarrays spanning nine tissue types predicted
      fourteen motifs as major regulators of age-dependent gene expression in human and
      mouse. The motif most strongly associated with aging was that of the
      transcription factor NF-kappaB. Inducible genetic blockade of NF-kappaB for 2 wk
      in the epidermis of chronologically aged mice reverted the tissue characteristics
      and global gene expression programs to those of young mice. Age-specific NF
      kappaB blockade and orthogonal cell cycle interventions revealed that NF-kappaB
      controls cell cycle exit and gene expression signature of aging in parallel but
      not sequential pathways. These results identify a conserved network of regulatory
      pathways underlying mammalian aging and show that NF-kappaB is continually
      required to enforce many features of aging in a tissue-specific manner.

PMID- 18055698
TI  - Respiratory syncytial virus: a sleeping giant?

PMID- 18055699
TI  - The COPD CO-factor.

PMID- 18055700
TI  - The role of inhaled corticosteroids in the management of acute asthma.

PMID- 18055701
TI  - Caring for the orphan's orphan: treatment of patients with portopulmonary
      hypertension.

PMID- 18055702
TI  - Translational research in respiratory medicine.

PMID- 18055703
TI  - Inflammatory cell microlocalisation and airway dysfunction: cause and effect?
AB  - Airway inflammation is a critical feature of the airway diseases asthma and
      chronic obstructive pulmonary disease (COPD). There is emerging evidence that
      structural cells play a key role in the development and perpetuation of the
      inflammatory response and are pivotal in the development of the changes in the
      airway structures that lead to airway remodelling. To date, little attention has
      been given to the localisation of inflammatory cells to airway structures or the
      potential interactions between these intimately located cells. However, it is
      likely that interactions between inflammatory and structural cells in the airway
      contribute enormously to the pathophysiology of asthma and COPD. Indeed, recent
      evidence suggests that mast cells localised to the airway smooth muscle bundle
      may be important in the development of airway hyperresponsiveness in asthma. In
      the present article, the authors aim to summarise: 1) the current understanding
      of which inflammatory cells locate to airway structures; 2) the proposed
      mechanisms that may be involved in mediating this microlocalisation; 3) the
      possible consequences of interactions between inflammatory and structural cells;
      and 4) the pressing need to investigate whether modulating these interactions is
      beneficial in asthma and chronic obstructive pulmonary disease.

PMID- 18055704
TI  - Evidence on measures for the prevention of ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia (VAP) continues to be an important cause of
      morbidity and mortality in ventilated patients. Evidence-based guidelines have
      been issued since 2001 by the European Task Force on ventilator-associated
      pneumonia, the Centers for Disease Control and Prevention, the Canadian Critical
      Care Society, and also by the American Thoracic Society and Infectious Diseases
      Society of America, which have produced a joint set of recommendations. The
      present review article is based on a comparison of these guidelines, together
      with an update of further publications in the literature. The 100,000 Lives
      campaign, endorsed by leading US agencies and societies, states that all
      ventilated patients should receive a ventilator bundle to reduce the incidence of
      VAP. The present review article is useful for identifying evidence-based
      processes that can be modified to improve patients' safety.

PMID- 18055705
TI  - The role of the nose in the pathogenesis of obstructive sleep apnoea and snoring.
AB  - Data from observational studies suggest that nasal obstruction contributes to the
      pathogenesis of snoring and obstructive sleep apnoea (OSA). To define more
      accurately the relationship between snoring, OSA and nasal obstruction, the
      current authors have summarised the literature on epidemiological and
      physiological studies, and performed a systematic review of randomised controlled
      trials in which the effects of treating nasal obstruction on snoring and OSA were
      investigated. Searches of bibliographical databases revealed nine trials with
      randomised controlled design. External nasal dilators were used in five studies,
      topically applied steroids in one, nasal decongestants in two, and surgical
      treatment in one study. Data from studies using nasal dilators, intranasal
      steroids and decongestants to relieve nasal congestion showed beneficial effects
      on sleep architecture, but only minor improvement of OSA symptoms or severity.
      Snoring seemed to be reduced by nasal dilators. Nasal surgery also had minimal
      impact on OSA symptoms. In conclusion, chronic nasal obstruction seems to play a
      minor role in the pathogenesis of obstructive sleep apnoea, and seems to be of
      some relevance in the origin of snoring. The impact of treating nasal obstruction
      in patients with snoring and obstructive sleep apnoea on long-term outcome
      remains to be defined through randomised controlled trials of medical and
      surgical therapies.

PMID- 18055706
TI  - Ventilator-associated lung injury: a search for better therapeutic targets.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent
      a continuum of injury that may arise from a number of primary insults. Localised
      injury may progress due to trauma from mechanical ventilation, a finding that has
      led to intense debate in the clinical and experimental literature over optimal
      ventilator management. The implementation of low tidal volume strategies has led
      to an improvement in outcomes; however, mortality remains unacceptably high. In
      the current review, ventilator-associated lung injury is examined, as it relates
      to the pathophysiological changes beyond direct airway trauma in ALI and ARDS,
      and an attempt is made to provide a historical perspective to outline potential
      current and future pitfalls in the use of surrogate end-points and the discovery
      of potential biomarkers. The systemic responses that lead to multi-organ
      dysfunction, the leading causes of morbidity and mortality in ALI and ARDS, are
      caused by pro-inflammatory signalling cascades and the activation of such diverse
      mediators as reactive oxygen species, immune response elements, apoptotic
      constituents and coagulation proteins. These areas are examined, including key
      mediators, and possible future areas of interest are discussed, including the
      potential of an "acute lung injury chip" to integrate measured surrogate
      biomarkers with real-time clinical information to improve patient outcomes.

PMID- 18055707
TI  - Pulmonary tumour with high carcinoembryonic antigen titre caused by chronic
      propolis aspiration.
AB  - Carcinoembryonic antigen (CEA) titre elevation is sometimes found in benign
      diseases, such as gastro-intestinal tract inflammatory disease and chronic
      obstructive pulmonary disease; however, very high CEA titre is rarely encountered
      in benign pulmonary disease. A 36-yr-old female, who had suffered from body
      weight loss, was found to have high serum CEA titre (60.8 ng.mL(-1)). Image
      studies revealed one pulmonary tumour at the left lower lobe, satellite nodules
      and mediastinal lymphadenopathy. Left lower lobectomy and lymph node dissection
      were performed for suspicious pulmonary malignancy. The pathological examination
      revealed that the tumourous lesion was composed of small and fragmented foreign
      bodies, fibrinopurulent exudate and heavy eosinophils. The bronchial epithelium
      was characterised by goblet cell hyperplasia and CEA overexpression. The
      remaining lung parenchyma possessed similar foreign body reaction. The patient's
      medical history was reviewed and it was found that she had spread propolis
      topically on nasal mucosa as an adjuvant therapy to asthma for 6 months prior to
      this medical event. The CEA titre decreased after the operation to 14.2 and 7.88
      ng.mL(-1) after 2 weeks and 6 months, respectively. Propolis is used widely in
      folk medicine but it also has strong sensitising potential. One rare case of
      propolis aspiration is reported with presentation mimicking lung cancer.

PMID- 18055708
TI  - Aqua jogging-induced pulmonary oedema.
AB  - The present study reports the case of a 43-yr-old very sporty male, who developed
      shortness of breath and expectorated bloody froth during aqua jogging. Pulmonary
      oedema was diagnosed clinically and by computed tomography of the chest. The
      patient made a full recovery and his echocardiography was entirely normal.
      Pulmonary oedema occurring in healthy scuba-divers and swimmers has been reported
      previously. However, this is the first case where pulmonary oedema was observed
      during aqua jogging.

PMID- 18055709
TI  - Quinolones to treat acute bacterial exacerbation of chronic bronchitis in TB
      endemic areas: a word of caution.

PMID- 18055710
TI  - Colistin as a first choice antibiotic for the initial empiric antimicrobial
      therapy of ventilator-associated pneumonia.

PMID- 18055712
TI  - Endometrial cancer: what is a clinician to do?

PMID- 18055713
TI  - When is a pathology review indicated in endometrial cancer?
AB  - OBJECTIVE: Discrepancies may exist between an original pathology report and
      formal pathology review, with subsequent implications for treatment. We conducted
      a study of pathology review in endometrial cancer from a population-based study
      to identify areas of discrepancy and effect on treatment. METHODS: This was a
      retrospective cohort study in Ontario, Canada from 1996 to 2000. We identified
      hysterectomy cases from patients with endometrial cancer that were subject to
      formal pathology review by a gynecologic pathologist at one of six tertiary care
      centers. Sarcomas and other rare histologic subtypes with fewer than five cases
      were excluded. We evaluated discrepancy between original pathology and review by
      demographics, stage, grade, and risk group. Four risk groups were defined: 1) low
      (stage I), 2) intermediate (stage I and II), 3) high-risk (stage I and II), and
      4) advanced stage (all stage III and IV). Reclassification from one risk group to
      another upon pathology review represented a potential change in treatment.
      Factors associated with significant discrepancy were identified by a
      multivariable logistic regression model. RESULTS: Formal pathology review was
      available on 450 cases. There were no differences by age, year, or hospital type.
      The overall discrepancy rate was 42.7% (95% confidence interval 38.2-47.3%). The
      intermediate-risk group had the highest rate of reclassification into another
      group (33.1%). The most significant rates of discrepancy were associated with
      endometrioid grades 2 and 3 tumors and stage IIA disease (39.8%, 50.9%, and
      79.6%, respectively). CONCLUSION: There was significant discrepancy between
      original pathology and formal review in endometrial cancer, with implications for
      guidelines on pathology review at a population level. LEVEL OF EVIDENCE: III

PMID- 18055714
TI  - Association of elevated C-reactive protein levels with an impaired prognosis in
      patients with surgically treated endometrial cancer.
AB  - OBJECTIVE: To evaluate whether C-reactive protein (CRP) serum levels are
      associated with prognosis in surgically treated endometrial cancer. METHODS: In
      the present multicenter study, CRP serum levels were measured preoperatively in
      403 surgically staged patients with endometrioid endometrial cancer. Results were
      correlated to clinical data. RESULTS: The mean (standard deviation) serum CRP
      level in patients with endometrial cancer was 1.0 (1.8) mg/dL. Serum CRP levels
      were associated with tumor stage (P=.01), but not with tumor grade (P=.8), lymph
      node involvement (P=.8), and age at diagnosis (P=.9). In a univariable survival
      analysis, serum CRP levels, tumor stage, tumor grade, and age at diagnosis were
      associated with disease-free and overall survival (all P <.001). In a
      multivariable Cox regression model, serum CRP levels (P=.001, P=.004), tumor
      stage (P <.001, P <.001), tumor grade (P=.02, P=.009), and age at diagnosis
      (P=.002, P=.001) were independent prognostic factors for disease-free and overall
      survival. CONCLUSION: Our results suggest that elevated serum CRP levels are
      associated with a less favorable prognosis in patients with surgically treated
      endometrial cancer. LEVEL OF EVIDENCE: II.

PMID- 18055715
TI  - Adjuvant radiotherapy in incompletely staged IC and II endometrioid uterine
      cancer.
AB  - OBJECTIVES: To estimate if adjuvant radiotherapy improves the disease-specific
      survival of patients with clinical stage IC and II endometrioid corpus cancer who
      did not undergo lymphadenectomy. METHODS: Information was obtained on patients
      with endometrioid corpus cancer from the National Cancer Institute database
      between 1988 and 2001. Data were analyzed using Kaplan-Meier and Cox proportional
      hazards regression methods. RESULTS: A total of 3,664 patients (median age 70
      years) with clinical stage IC to II endometrioid carcinoma did not undergo
      lymphadenectomy, of which 2,170 had stage IC and 1,494 stage II disease. Of
      these, 1,175 had grade 1, 1,637 had grade 2, 693 had grade 3, and in 159, grade
      was unknown. The 5-year disease-specific survival rates of clinical stage IC
      compared with stage II patients were 91.3% and 86.7% (P<.001). Of the 1,964 who
      received adjuvant radiotherapy, the 5-year disease-specific survival rate was
      89.9% compared with 87.8% in those who did not undergo further treatment (P=.04).
      Adjuvant radiation improved the disease-specific survival rate of those with
      stage II disease, (86.5% compared with 81.9%; P=.02), but not in those with stage
      IC disease (91.7% compared with 92.6%; P=.68). The benefit of radiotherapy was
      significant in patients with grade 3 disease and patients 70 years or older
      (88.2% compared with 83.3%; P<.001). On multivariable analysis, age, stage, and
      grade were significant independent prognostic factors for disease-specific
      survival. CONCLUSION: Adjuvant radiotherapy marginally improved the survival of
      clinically staged IC-II endometrioid uterine cancer patients without
      lymphadenectomy. After excluding those without hysterectomy, radiotherapy did not
      significantly affect disease-specific survival. LEVEL OF EVIDENCE: II.

PMID- 18055716
TI  - Comparative measurement of pelvic floor pain sensitivity in chronic pelvic pain.
AB  - OBJECTIVE: Women with pelvic pain conditions exhibit enhanced somatic pain
      sensitivity at extragenital sites. Whether comparable differences exist for
      pelvic floor or vaginal pain sensitivity is unknown. The present study was
      undertaken to estimate pelvic floor and vaginal pressure-pain detection
      thresholds both in women with pelvic pain and healthy women. METHODS: We
      conducted a cross-sectional study of pelvic floor and vaginal pain detection
      thresholds comparing 14 women with chronic pelvic pain to 30 healthy women
      without this condition. Using a prototype vaginal pressure algometer, we recorded
      continuous ascending pressure and determined each subject's pressure-pain
      threshold at each of eight paired pelvic floor sites and two adjacent vaginal
      sites. RESULTS: Mean pain detection thresholds for all 10 sites were
      significantly lower in women with pelvic pain compared with healthy controls (at
      right iliococcygeus, controls 1.73+/-0.60 kg/cm(2) compared with women 0.96+/
      0.38 kg/cm(2), P<.001, other sites similar), and remained so after controlling
      for differences in patient age and menopausal status. Pelvic floor and vaginal
      site pain detection thresholds had moderate-to-strong correlations with each
      other (r=0.62-0.91). CONCLUSION: Chronic pelvic pain is associated with enhanced
      pelvic floor and vaginal pressure-pain sensitivity. LEVEL OF EVIDENCE: II.

PMID- 18055717
TI  - Pregnancy outcomes for women with placenta previa in relation to the number of
      prior cesarean deliveries.
AB  - OBJECTIVE: To estimate the association between the number of prior cesarean
      deliveries and pregnancy outcomes among women with placenta previa. METHODS:
      Women with a placenta previa and a singleton gestation were identified in a
      concurrently collected database of cesarean deliveries performed at 19 academic
      centers during a 4-year period. Maternal and perinatal outcomes were analyzed
      after stratifying by the number of cesarean deliveries before the index
      pregnancy. RESULTS: Of the 868 women in the analysis, 488 had no prior cesarean
      delivery, 252 had one prior cesarean delivery, 76 had two prior cesarean
      deliveries, and 52 had at least three prior cesarean deliveries. Multiple
      measures of maternal morbidity (eg, coagulopathy, hysterectomy, pulmonary edema)
      increased in frequency as the number of prior cesarean deliveries rose. Even one
      prior cesarean delivery was sufficient to increase the risk of an adverse
      maternal outcome (a composite of transfusion, hysterectomy, operative injury,
      coagulopathy, venous thromboembolism, pulmonary edema, or death) from 15% to 23%,
      which corresponded, in multivariable analysis, to an adjusted odds ratio of 1.9
      (95% confidence interval 1.2-2.9). Conversely, gestational age at delivery and
      adverse perinatal outcome (a composite measure of respiratory distress syndrome,
      necrotizing enterocolitis, intraventricular hemorrhage grade 3 or 4, seizures, or
      death) were unrelated to the number of prior cesarean deliveries. CONCLUSION:
      Among women with a placenta previa, an increasing number of prior cesarean
      deliveries is associated with increasing maternal, but not perinatal, morbidity.
      LEVEL OF EVIDENCE: II.

PMID- 18055718
TI  - Reduced fertility after cesarean delivery: a maternal choice.
AB  - OBJECTIVE: To explore the association between mode of delivery and subsequent
      fertility. METHODS: Deliveries registered in the Medical Birth Registry of Norway
      were linked to mothers through national identification numbers. The study
      population was 596,341 women who had their first delivery during 1967-1996, and
      who were followed up through 2003. We compared rates of continuation to a
      subsequent birth according to mode of previous delivery (cesarean compared with
      vaginal). RESULTS: If the first child survived the first year of life, cesarean
      delivery was associated with a significantly reduced probability of a second
      birth (relative risk [RR] 0.82, 95% confidence interval [CI] 0.81-0.83 during
      1967-1981, and RR 0.88, 95% CI 0.88-0.89 during 1982-1996). Following a
      stillbirth or an infant loss, the association was less strong during 1967-1981
      (RR 0.93, 95% CI 0.89-0.97) and no longer significant during 1982-1996 (RR 1.00,
      95% CI 0.97-1.03). A similar pattern was observed from the second to the third
      birth and in subgroup analyses of women with preeclampsia or breech presentation
      and in an obstetric low-risk group. CONCLUSION: Cesarean delivery was more
      strongly associated with reduced fertility if the infant survived than if it was
      stillborn or died. This suggests that the reduced fertility was to a large degree
      voluntary and not related to the indication, nor to any physical consequence, of
      the cesarean delivery. LEVEL OF EVIDENCE: II.

PMID- 18055719
TI  - Association between rising professional liability insurance premiums and primary
      cesarean delivery rates.
AB  - OBJECTIVE: To estimate the association between changes in Illinois professional
      liability premiums for obstetrician-gynecologists and singleton primary cesarean
      delivery rates. METHODS: Data from the National Center for Health Statistics were
      used to identify all singleton births between 37 weeks and 44 weeks of gestation
      occurring in Illinois from 1998 through 2003. Primary cesarean delivery rates for
      women delivered between 37 weeks and 44 weeks of gestation per 1,000 gravid women
      eligible to have a primary cesarean delivery were calculated for each Illinois
      county. The annual medical professional liability premium for each county in
      Illinois was represented by the reported professional liability insurance rate
      charges (adjusted to 2004 dollars) from the ISMIE Mutual Insurance Company.
      Separate analyses were conducted for nulliparous and multiparous women. The
      independent association between county-level primary cesarean delivery rates and
      the previous year's insurance premiums was evaluated using linear regression
      models. RESULTS: During the study period, 817,521 women were eligible for
      inclusion in the analysis. The county-level mean primary cesarean delivery rate
      increased from 126 to 163 per 1,000 (P<.001) eligible women, whereas the mean
      annual medical professional liability insurance premiums also rose significantly
      (from $60,766 in 1997 to $83,167 in 2002, P<.001). Multivariable analyses
      demonstrated that for each annual $10,000 insurance premium increase, the primary
      cesarean delivery rate increased by 15.7 per 1,000 for nulliparous women. This
      association also was evident for multiparous women, who had an increase in
      cesarean deliveries of 4.7 per 1,000 for every $10,000 increase. CONCLUSION:
      Higher rates of primary cesarean delivery are associated with increased medical
      professional liability premiums for obstetrician-gynecologists in Illinois. LEVEL
      OF EVIDENCE: II.

PMID- 18055720
TI  - Use of recombinant activated factor VII in primary postpartum hemorrhage: the
      Northern European registry 2000-2004.
AB  - OBJECTIVE: To collect data from nine European countries for cases of obstetric
      hemorrhage between 2000 and 2004 in which recombinant activated factor VII
      (rFVIIa) was used. METHODS: The cases were identified through national surveys.
      Standardized case report forms included sociodemographic details, past medical
      and obstetric history, and details of the progress and management of labor in
      which the postpartum hemorrhage occurred. Clinicians were asked to describe
      subjectively the effect of rFVIIa administration using two mutually exclusive
      categories: 1) bleeding reduced or 2) bleeding unchanged or worse. RESULTS: A
      total of 113 forms were returned (88%) with 97 (86%) classified as treatment, and
      16 (14%) as "secondary prophylaxis." Clinicians noted improvements after a single
      dose for 80% of women in the treatment group, and for 75% in the secondary
      "prophylaxis" group. However, rFVIIa failed in 15 cases (13.8%). Few serious
      adverse events were noted related to rFVIIa administration; there were four cases
      of thromboembolism, one myocardial infarction, and one skin rash. CONCLUSION:
      Clinical reports and hematologic data suggest improvement for more than 80% of
      women after rFVIIa administration and few adverse effects. LEVEL OF EVIDENCE: II.

PMID- 18055721
TI  - Hysterectomy compared with endometrial ablation for dysfunctional uterine
      bleeding: a randomized controlled trial.
AB  - OBJECTIVE: To compare the effectiveness of hysterectomy and endometrial ablation
      in women with dysfunctional uterine bleeding. METHODS: The Surgical Treatments
      Outcomes Project for Dysfunctional Uterine Bleeding was a multicenter, randomized
      controlled trial. Eligible women were premenopausal with dysfunctional uterine
      bleeding and aged 18 years or older. Primary outcomes were problems that led the
      woman to seek care solved, bleeding, pain, and fatigue at 12 months. Additional
      outcomes included quality of life, adverse events, reoperation, and others at 24
      months and up to 5 years. RESULTS: We randomly assigned 237 women between January
      1998 and June 2001. Follow-up ended in June 2003. We completed 24 months of
      follow-up on 114 of 123 women assigned to endometrial ablation and 111 of 114
      assigned to hysterectomy. Approximately 85% of women were aged younger than 45
      years; 76.4% classified themselves as white, 18.6% as African American, less than
      1% as Asian, 4.6% as American Indian, and 8.4% as Hispanic (classification within
      more than one category possible). Both endometrial ablation and hysterectomy were
      effective at 24 months in solving the problem that led women to seek care (84.9%
      compared with 94.4%), and in relieving bleeding, pain, fatigue, and other
      symptoms, although hysterectomy was more effective for bleeding. By 48 months, 32
      of the 110 women initially receiving endometrial ablation required reoperation.
      Adverse events were more frequent with hysterectomy. CONCLUSION: Both endometrial
      ablation and hysterectomy are effective treatments in women with dysfunctional
      uterine bleeding. Hysterectomy (as the index surgery) was associated with more
      adverse events and a substantial number of patients receiving endometrial
      ablation had reoperation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT00114088 LEVEL OF EVIDENCE: I.

PMID- 18055722
TI  - Physical functioning and menopause states.
AB  - OBJECTIVE: To assess whether losses in physical functioning are related to the
      natural menopause, hysterectomy, or calendar time during midlife, after
      adjustment for body size and smoking. METHODS: A longitudinal assessment of
      physical functioning was conducted from 2000/01 through 2005/06 in a population
      based sample of 544 women at midlife enrolled in the Michigan Bone Health and
      Metabolism Study. Longitudinal mixed models were used to relate menopausal status
      to measures of physical functioning. Perception of physical functioning was
      assessed with the Medical Outcomes Study Short-Form 36 questionnaire. Eight
      performance-based measures of physical functioning were also included. RESULTS:
      Women with hysterectomy (with or without estrogen from ovarian conservation or
      exogenous replacement) had reduced levels of functioning and greater rates of
      change in the 2-lb lift (P<.005), sit-to-stand (P<.01), timed stair climb
      (P<.01), timed walk (P<.01), velocity (P<.05), and perception of physical
      functioning (P<.01) compared with premenopausal and perimenopausal women after
      adjustment for time since baseline, body size, and smoking. Diminished
      functioning in postmenopausal women was observed in hand grip (P<.005), 2-lb lift
      (P<.05), sit-to-stand (P<.05), velocity (P<.05), and perceived physical
      functioning (P<.05). Based on regression analyses, there was greater loss in
      women with hysterectomy compared with natural menopause. Level of functioning
      among postmenopausal women with exogenous hormone replacement was similar to
      premenopausal women on eight of nine physical functioning measures. CONCLUSION:
      Hysterectomy, even with availability of an estrogen source, seems to be a "risk"
      state for diminishing physical function at midlife, and this may initiate a
      vulnerable stage for future compromised quality of life. LEVEL OF EVIDENCE: II.

PMID- 18055723
TI  - Can we use a catheter to do the q-tip test?
AB  - OBJECTIVE: To compare two commonly used modifications to the standard Q-tip test
      for urethral hypermobility: catheter alone and catheter with Q-tip. METHODS: All
      women referred for the evaluation of urinary incontinence or pelvic organ
      prolapse were included in the study. A postvoid residual urine was collected on
      each patient and the angle of the urethra with the horizontal plane was measured
      at rest and with Valsalva with the Q-tip, catheter alone, and catheter with Q
      tip. The test was considered positive if the angle of excursion was 30 degrees or
      more. RESULTS: In this group of 100 consecutive women with urinary incontinence
      or pelvic organ prolapse, the mean change in the angle was significantly
      different from the standard Q-tip test (51 degrees) when catheter alone (35
      degrees, P<.001) or catheter with Q-tip modifications were used (44 degrees,
      P<.001). This difference was due to a significant reduction in the resting and
      Valsalva maneuver angles with the catheter alone, and a significant decrease only
      in the Valsalva maneuver angle with the catheter with Q-tip method (P<.001). The
      percentage of positive tests for the standard Q-tip test (92%) was significantly
      different from the catheter only method (63%, P<.001), and from the catheter with
      Q-tip technique (83%, P=.021). The "best match" values of 10 degrees for the
      catheter alone, and 15 degrees for the catheter with Q-tip methods produce the
      best equivalent results at this time. CONCLUSION: The use of a catheter, instead
      of a Q-tip, in the evaluation of urethral hypermobility resulted in reduced
      angles of excursion from resting to Valsalva maneuver. LEVEL OF EVIDENCE: III.

PMID- 18055724
TI  - Analysis of arterial blood vessels surrounding the myoma: relevance to
      myomectomy.
AB  - OBJECTIVE: The optimal direction of myomectomy incision in relation to the blood
      vessels is unclear. Accordingly, we evaluated the location and course of arterial
      blood vessels surrounding the myoma. METHODS: This study is a retrospective
      analysis of 592 arterial blood vessels in 60 patients with symptomatic uterine
      leiomyomata undergoing uterine artery embolization. RESULTS: We encountered 592
      arterial blood vessels surrounding the myoma. The vessels could be seen
      encircling the surface of the myoma. The dominant myoma was located on anterior
      (n=30), posterior (n=17), and fundal part of the uterus (n=13). There was no
      difference in the diameter (6.9+/-2.7 cm, 5.8+/-0.7 cm, and 6.7+/-0.5 cm) and
      volume of the myoma (268.6+/-52.7 cm(3), 197.0+/-64.5 cm(3), and 199.3+/-40.5
      cm(3)) among anterior, posterior, and fundal, respectively. The vessels were
      graded as coursing with angles of 0-30 degrees, 30-60 degrees, and 60-90 degrees.
      There were significantly more blood vessels in the 30-60 degree group among
      anterior myoma (n=88, 42.5%) than in 0-30 degree (n=59, 28.5%, P=.004, 95%
      confidence interval [CI] 0.36-0.81) and 60-90 degree groups (n=60, 29.0%, 95% CI
      1.2-2.7). Similar findings were found among posterior myoma (0-30 degrees n=26,
      21.7%; 30-60 degrees n=59, 49.2%; P<.001, 95% CI 0.16-0.50; 60-90 degrees 35
      (29.2%), P<.002, 95% CI 1.37-3.9). Among fundal myomas, there was no difference
      in the number of vessels in the 0-30 degree (n=28, 28.6%), 60-90 degree (n=40,
      40.8%), and in 60-90 degree groups (n=30, 30.6%). CONCLUSION: Arterial blood
      vessels travel mostly diagonally on the surface of anterior and posterior myomas.
      There was no predominant pattern in the course of the arteries on fundal myomas.
      These findings suggest that regardless of the direction of the myomectomy
      incision, arterial blood vessels on myoma surface could be injured. LEVEL OF
      EVIDENCE: II.

PMID- 18055725
TI  - Mifepristone in second-trimester medical abortion: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the adjunctive use of mifepristone in second-trimester
      induction abortions using misoprostol 1 day after feticidal digoxin. METHODS:
      This is a randomized, placebo-controlled, double-blind trial of mifepristone in
      second-trimester induction termination using misoprostol after feticidal digoxin.
      Women seeking abortion between 18 and 23 weeks of gestation were offered
      enrollment. At the time of digoxin amnioinfusion, participants received a
      randomly allocated, identical-appearing capsule containing either mifepristone,
      200 mg, or placebo. Patients returned the following day for induction with buccal
      misoprostol. The primary outcome was the time interval from the first misoprostol
      dose to abortion. Analysis utilized survival curves with log-rank testing.
      RESULTS: Of 64 women, 32 received mifepristone and 32 received placebo. The
      groups did not differ by ethnicity, age, parity, reason for termination, or
      gestational age. Median procedure time was significantly shorter for those who
      received mifepristone, 10 hours (95% confidence interval [CI] 8-12), than those
      who did not, 18 hours (95% CI 15-22), P<.01, and those parous, 10 hours (95% CI 9
      14), compared with nulliparous, 16 hours (95% CI 12-22, P=.02). Other findings in
      the mifepristone compared with placebo group included rates of placental
      retention, 3.1% compared with 6.3% (P=.61), length of hospitalization, 0.66 days
      compared with 0.8 days (P=.23), and analgesic requirements, 27.2 mg compared with
      39.3 mg morphine (P=.22). Side effects during induction were similar between
      groups. CONCLUSION: Addition of mifepristone in second-trimester termination
      inductions using misoprostol significantly reduces the abortion time interval.
      CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov,
      NCT00382538 LEVEL OF EVIDENCE: I.

PMID- 18055726
TI  - Antioxidant therapy to prevent preeclampsia: a randomized controlled trial.
AB  - OBJECTIVE: To study whether antioxidant supplementation will reduce the incidence
      of preeclampsia among patients at increased risk. METHODS: A randomized, placebo
      controlled, double-blind clinical trial was conducted at four Brazilian sites.
      Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have
      chronic hypertension or a prior history of preeclampsia were randomly assigned to
      daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International
      Units) or placebo. Analyses were adjusted for clinical site and risk group (prior
      preeclampsia, chronic hypertension, or both). A sample size of 734 would provide
      80% power to detect a 40% reduction in the risk of preeclampsia, assuming a
      placebo group rate of 21% and alpha=.05. The alpha level for the final analysis,
      adjusted for interim looks, was 0.0458. RESULTS: Outcome data for 707 of 739
      randomly assigned patients revealed no significant reduction in the rate of
      preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of
      352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61-1.25]). There
      were no differences in mean gestational age at delivery or rates of perinatal
      mortality, abruptio placentae, preterm delivery, and small for gestational age or
      low birth weight infants. Among patients without chronic hypertension, there was
      a slightly higher rate of severe preeclampsia in the study group (study drug,
      6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio
      2.78, 95% confidence interval 0.79-12.62). CONCLUSION: This trial failed to
      demonstrate a benefit of antioxidant supplementation in reducing the rate of
      preeclampsia among patients with chronic hypertension and/or prior preeclampsia.
      CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov,
      NCT00097110 LEVEL OF EVIDENCE: I.

PMID- 18055727
TI  - Primary preeclampsia in the second pregnancy: effects of changes in prepregnancy
      body mass index between pregnancies.
AB  - OBJECTIVE: To examine the association between changes in prepregnancy body mass
      index (BMI) between a woman's first two pregnancies and incidence of preeclampsia
      in the second pregnancy. METHODS: We performed a population-based retrospective
      cohort analysis using data on women's first two singleton pregnancies (n=136,884)
      in Missouri (1989-1997). The study was restricted to women without preeclampsia
      in the first pregnancy. Prepregnancy BMI (kg/m(2)) was categorized as underweight
      (less than 18.5), normal (18.5-24.9), overweight (25-29.9), and obese (30 or
      greater). Analyses were adjusted for confounders through multivariable logistic
      regression. RESULTS: The incidence rate of preeclampsia in the second pregnancy
      was 2.0%. In comparison with women who were of normal BMI in both pregnancies,
      the risk for preeclampsia increased when BMI changed between the first two
      pregnancies from underweight to obese (odds ratio [OR] 5.6, 95% confidence
      interval [CI] 1.7-18.2), normal to overweight (OR 2.0, 95% CI 1.7-2.3), normal to
      obese (OR 3.2, 95% CI 2.5-4.2), and overweight to obese (OR 3.7, 95% CI 3.1-4.3).
      Being obese or overweight in both pregnancies was associated with increased risk
      of preeclampsia in the second pregnancy. Women who increased their BMI from
      underweight to normal or overweight between pregnancies had risks of preeclampsia
      comparable with those with normal BMI in both pregnancies. African-American, but
      not white, women who had a reduction in BMI from obese or overweight to normal
      between pregnancies remained at increased risk for preeclampsia. CONCLUSION:
      Increases in prepregnancy BMI from normal weight to overweight or obese between
      pregnancies are associated with increased risk of preeclampsia in the subsequent
      pregnancy. LEVEL OF EVIDENCE: II.

PMID- 18055728
TI  - Infertility, infertility treatment, and fetal growth restriction.
AB  - OBJECTIVE: To examine the association between infertility, with or without
      treatment, and fetal growth, as well as perinatal and infant mortality. METHODS:
      From the Danish National Birth Cohort (1997-2003), we identified 51,041
      singletons born of fertile couples (time to pregnancy 12 months or less), 5,787
      born of infertile couples conceiving naturally (time to pregnancy more than 12
      months), and 4,317 born after treatment. We defined small for gestational age
      (SGA) as the lowest 5% of birth weight by sex and gestational age. RESULTS: Crude
      estimates suggested an increased risk of perinatal mortality and SGA among
      infertile couples (treated and untreated), but the odds ratios (ORs) of perinatal
      mortality among infertile couples were attenuated after adjustment for maternal
      age and body mass index (1.32, 95% confidence interval [CI] 0.95-1.84 among
      untreated and 1.26, 95% CI 0.86-1.85 among treated couples). The elevated risk of
      SGA among infertile couples persisted after adjustment for maternal age, parity,
      and smoking (OR 1.24, 95% CI 1.10-1.40 among untreated, and OR 1.40, 95% CI 1.23
      1.60 among treated). The risk of SGA increased with time to pregnancy, and a
      longer time to pregnancy was associated with a small reduction in birth weight
      across the whole distribution. CONCLUSION: The increased risk of SGA observed
      among infertile couples with or without infertility treatment suggests that
      infertility may be a risk factor for intrauterine growth restriction. Treatment
      per se may have little effect on fetal growth. A small-to-moderate increased risk
      of perinatal mortality in infertile couples cannot be ruled out due to the small
      number of cases. LEVEL OF EVIDENCE: II.

PMID- 18055729
TI  - Monocyte major histocompatibility complex class II expression in term and preterm
      labor.
AB  - OBJECTIVE: To investigate how term and preterm labor (PTL) influence the balance
      between maternal proinflammatory and antiinflammatory responses as measured by
      expression of major histocompatibility complex (MHC) Class II on maternal
      monocytes and tumor necrosis factor-alpha (TNF-alpha) production by in vitro
      stimulation of whole blood by lipopolysaccharide (LPS). METHODS: Blood was taken
      from the following women (n=118): term elective cesarean delivery or in
      spontaneous labor, in premature labor, or with preterm premature rupture of the
      membranes (PROM) at less than 32 weeks, and gestation-matched reference group.
      Monocyte MHC Class II expression was measured by flow cytometry using a dual
      staining technique. Plasma cytokine levels were assayed using a cytometric bead
      array system. In vitro whole blood stimulation with LPS was also performed, and
      cytokine production was measured. RESULTS: Term labor was associated with a fall
      in the percentage of monocytes expressing MHC Class II, compared with third
      trimester of pregnancy, P<.05 and a reduction in LPS-stimulated TNF-alpha
      production. This fall in MHC Class II was even more pronounced in PTL and preterm
      PROM groups compared with the reference group, P<.01. CONCLUSION: There was
      evidence of reduced expression of monocyte MHC Class II and LPS-stimulated TNF
      alpha in term and preterm labor. This pattern of reduced MHC Class II expression
      and reduced TNF-alpha production is known as monocyte hyporesponsiveness or
      immune paresis. Detection of this state may provide insights into the maternal
      inflammatory status and be of use in the management of women with threatened PTL
      or preterm PROM. LEVEL OF EVIDENCE: II.

PMID- 18055730
TI  - External cephalic version for breech presentation with or without spinal
      analgesia in nulliparous women at term: a randomized controlled trial.
AB  - OBJECTIVE: To compare the success of external cephalic version using spinal
      analgesia with no analgesia among nulliparas. METHODS: A prospective randomized
      controlled trial was performed in a tertiary referral center delivery suite.
      Nulliparous women at term requesting external cephalic version for breech
      presentation were randomized to receive spinal analgesia (7.5 mg bupivacaine) or
      no analgesia before the external cephalic version. An experienced obstetrician
      performed the external cephalic version. Primary outcome was successful
      conversion to vertex presentation. RESULTS: Seventy-four women were enrolled, and
      70 analyzed (36 spinal, 34 no analgesia). Successful external cephalic version
      occurred among 24 of 36 (66.7%) women randomized to receive spinal analgesia
      compared with 11 of 34 (32.4%) without, P=.004 (95% confidence interval [CI] of
      the difference: 0.0954-0.5513). External cephalic version with spinal analgesia
      resulted in a lower visual analog pain score, 1.76+/-2.74 compared with 6.84+/
      3.08 without, P<.001. A secondary analysis logistic regression model demonstrated
      that the odds of external cephalic version success was 4.0-fold higher when
      performed with spinal analgesia P=.02 (95% CI, odds ratio [OR] 1.2-12.9).
      Complete breech presentation before attempting external cephalic version
      increased the odds of success 8.2-fold, P=.001 (95% CI, OR 2.2-30.3). Placental
      position, estimated fetal weight, and maternal weight did not contribute to the
      success rate when spinal analgesia was used. There were no cases of placental
      abruption or fetal distress. CONCLUSION: Administration of spinal analgesia
      significantly increases the success rate of external cephalic version among
      nulliparous women at term, which allows possible normal vaginal delivery.
      CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov,
      NCT00119184 LEVEL OF EVIDENCE: I.

PMID- 18055731
TI  - Constipation in pregnancy: prevalence, symptoms, and risk factors.
AB  - OBJECTIVE: To prospectively estimate constipation prevalence and risk factors in
      pregnancy. METHODS: We enrolled healthy pregnant women in this longitudinal study
      during the first trimester. At each trimester and 3 months postpartum,
      participants completed a self-administered bowel symptom questionnaire, physical
      activity and dietary fiber intake measures, and a prospective 7-day stool diary.
      Constipation was defined using the Rome II criteria (presence of at least two of
      the following symptoms for at least one quarter of defecations: straining, lumpy
      or hard stools, sensation of incomplete evacuation, sensation of anorectal
      obstruction, manual maneuvers to facilitate defecation, and fewer than three
      defecations per week). Generalized linear logistic models explored factors
      associated with constipation during pregnancy. RESULTS: One hundred three women
      were enrolled with mean (+/-standard deviation) age of 28 (+/-5) years; 54% were
      nulliparous and 92% white. Constipation prevalence rates were 24% (95% confidence
      interval [CI] 16-33%), 26% (95% CI 17-38%), 16% (95% CI 8-26%), and 24% (95% CI
      13-36%) in the first, second, and third trimesters and 3 months postpartum,
      respectively. Additionally, irritable bowel syndrome (by Rome II criteria)
      prevalence rates were 19% (95% CI 12-28%), 13% (95% CI 6-23%), 13% (95% CI 6-23%)
      and 5% (95% CI 1-13%) in the first, second, and third trimesters and 3 months
      postpartum, respectively. In multivariable longitudinal analysis, iron
      supplements (OR 3.5, 95% CI 1.04-12.10) and past constipation treatment (OR 3.58,
      95% CI 1.50-8.57) were associated with constipation during pregnancy. CONCLUSION:
      Constipation measured using the Rome II criteria affects up to one fourth of
      women throughout pregnancy and at 3 months postpartum. LEVEL OF EVIDENCE: II.

PMID- 18055732
TI  - Maternal smoking: effect on circulating cell-free fetal and total DNA levels in
      maternal plasma from the second trimester.
AB  - OBJECTIVE: To estimate whether potential clinical applications of cell-free fetal
      and total DNA in the field of noninvasive prenatal diagnosis need to be adjusted
      for maternal smoking status. METHODS: In this study, using 344 maternal blood
      samples from the second trimester of pregnancy, circulating cell-free DNA in
      maternal plasma samples, specific for the SRY and DYS14 loci (representing fetal
      DNA) and GAPDH sequence (representing total genomic DNA) were quantified by real
      time polymerase chain reaction. RESULTS: Fetal sex determination was 100%
      accurate using a combination of probes for SRY and DYS14. The levels of DYS14 and
      SRY detected were significantly correlated (r=0.884, P<.001). No significant
      difference was seen between the quantitative levels of cell-free male fetal DNA
      between the smoking groups and control group. Similarly, no significant
      difference was seen in the amount of total cell-free DNA in the study population.
      CONCLUSION: In contrast to first- and second-trimester screening assays for Down
      syndrome, where smoking status significantly affect levels of maternal serum
      analytes, smoking status does not affect quantitative levels of cell-free fetal
      DNA or total cell-free DNA in maternal plasma. LEVEL OF EVIDENCE: II.

PMID- 18055733
TI  - Prenatal herpes simplex virus serologic screening beliefs and practices among
      obstetricians.
AB  - OBJECTIVE: To describe the beliefs and practices of obstetricians related to
      prenatal serologic testing for HSV infection. METHODS: A total of 265 (73% of
      eligible) currently practicing obstetricians in Washington State completed a 36
      question mailed survey that assessed beliefs regarding genital herpes in
      pregnancy, neonatal herpes, serologic testing for herpes in pregnancy, and ease
      of testing. RESULTS: Ninety-five percent of respondents believed genital herpes
      was common in reproductive-aged women, 83% believed neonatal herpes was a serious
      health issue, and 73% believed it warranted systematic prevention efforts; 74%
      discussed herpes with pregnant patients as part of prenatal care, 31% provided
      written materials about herpes, and 15% used serologic tests for herpes in 75% or
      more of their prenatal patients. Factors independently associated with routine
      herpes serologic testing were academic practice setting (adjusted odds ratio
      [aOR] 10.4, 95% confidence interval [CI] 2.8-39.1) and metropolitan practice
      setting (aOR 3.3, 95% CI 1.4-7.9). Beliefs that testing would cause unnecessary
      distress in pregnancy (aOR 0.3, 95% CI 0.1-0.7), or that testing was not worth
      the expense (aOR 0.1, 95% CI 0.0-0.6) were associated with not testing.
      Availability of serologic tests for HSV was reported to be high and was not
      associated with prenatal HSV testing. CONCLUSION: Most obstetricians believe
      neonatal herpes prevention is important. LEVEL OF EVIDENCE: II.

PMID- 18055734
TI  - Changes in prescription contraceptive use, 1995-2002: the effect of insurance
      status.
AB  - OBJECTIVE: To examine changes in prescription contraception use between 1995 and
      2002 by insurance status among women at risk for unintended pregnancy. METHODS:
      Data from the National Survey of Family Growth, including 4,767 women at risk of
      unintended pregnancy in 1995 and 3,569 in 2002, were used to evaluate changes in
      primary contraception methods by health insurance status and year of survey.
      Logistic regression models tested differences in the likelihood of prescription
      contraceptive use among privately insured, publicly insured, and uninsured women
      in each year, after controlling for age, race and ethnicity, education, income,
      employment, marital status, number of children, religion, and self reported
      overall health. RESULTS: Overall prescription contraceptive use increased between
      1995 and 2002 by 3% (48.9% to 51.9%, P=.049). Nonuse of contraception also
      increased (11.6% to 16.1%, P<.001). The change in the likelihood of prescription
      contraceptive use was greatest and only significant among privately insured women
      (+5.5%, P=.002). In multiple regression analysis, women in 1995 were 10% less
      likely to report use of prescription contraceptives compared with women in 2002
      (relative risk 0.90, 95% confidence interval 0.82-0.98), and uninsured women were
      more than 20% less likely to report prescription contraceptive use compared with
      privately insured women (relative risk 0.78, 95% confidence interval 0.67-0.90).
      CONCLUSION: Prescription contraceptive use increased most significantly among
      privately insured women between 1995 and 2002, potentially reflecting state
      mandates enacted during that period requiring contraceptive coverage by private
      insurers. It is important for clinicians to understand these differences and
      address issues of insurance coverage with patients when discussing contraceptive
      options. LEVEL OF EVIDENCE: III.

PMID- 18055735
TI  - Advance provision of emergency contraception for pregnancy prevention: a meta
      analysis.
AB  - OBJECTIVE: Advance provision of emergency contraception can circumvent some
      obstacles to timely use. We performed a meta-analysis to summarize randomized
      controlled trials evaluating advance provision of emergency contraception to
      explore effects on pregnancy rates, sexually transmitted infections, and sexual
      and contraceptive behaviors. DATA SOURCES: In August 2006, we searched CENTRAL,
      EMBASE, POPLINE, MEDLINE, a specialized emergency contraception article database,
      and contacted experts to identify published or unpublished trials. METHODS OF
      STUDY SELECTION: We included randomized controlled trials comparing advance
      provision to standard access, defined as any of the following: counseling (with
      or without information about emergency contraception) or provision of emergency
      contraception on request at a clinic or pharmacy. TABULATION, INTEGRATION AND
      RESULTS: Two reviewers independently assessed study quality. We performed a meta
      analysis using Review Manager software. Eight randomized controlled trials met
      inclusion criteria, representing 6,389 patients in the United States, China, and
      India. Advance provision did not decrease pregnancy rates, despite increased use
      (single use, odds ratio [OR] 2.52, 95% confidence interval [CI] 1.72-3.70;
      multiple use: OR 4.13, 95% CI 1.77-9.63) and faster use (weighted mean difference
      -14.6 hours, 95% CI -16.77 to -12.4 hours). Advance provision did not increase
      rates of sexually transmitted infections (OR 0.99, 95% CI 0.73-1.34), unprotected
      intercourse, or changes in contraceptive methods. Women who received emergency
      contraception in advance were as likely to use condoms as other women.
      CONCLUSION: Advance provision of emergency contraception did not reduce pregnancy
      rates and did not negatively affect sexual and reproductive health behaviors and
      outcomes compared with conventional provision. LEVEL OF EVIDENCE: III.

PMID- 18055736
TI  - Are doctors prepared for direct-to-consumer advertising of genetics tests?

PMID- 18055737
TI  - ASHG Statement* on direct-to-consumer genetic testing in the United States.

PMID- 18055738
TI  - Accreditation, certification: why all the confusion?
AB  - Tremendous confusion exists concerning the issues of physician certification and
      practice accreditation in obstetric and gynecologic ultrasonography.
      Certification speaks to physician competence. All obstetrician-gynecologists who
      have finished residency training since 1982 are deemed "competent" to perform
      obstetric and gynecologic ultrasonography by virtue of their training. Those
      trained before 1982 need to be able to describe their level of experience in
      performing obstetric and gynecologic ultrasonography. Accreditation deals with
      issues of patient safety and quality control, including equipment calibration,
      transducer cleaning and disinfection, universal precautions and Occupational
      Safety and Health Administration regulations, ultrasound examination protocols,
      and qualifications of nonphysician personnel performing ultrasound examinations.
      A new field of radiology benefit managers has arisen in response to attempts by
      health insurers to manage care, and reduce their costs and utilization. They have
      adopted ultrasound accreditation, originally intended to enhance patient safety,
      to help restrict utilization. Currently two organizations are recognized as
      accrediting bodies: The American Institute of Ultrasound in Medicine (AIUM),
      which recognizes obstetric and gynecologic residency training as evidence of
      competency, and The American College of Radiologists, which does not.
      Obstetrician-gynecologists should realize that AIUM's accreditation is their
      "lifeboat" in this time of increasing interference by health care insurers into
      decision making in clinical practice.

PMID- 18055739
TI  - Preventing needlestick injuries in obstetrics and gynecology: how can we improve
      the use of blunt tip needles in practice?
AB  - Surgical needlestick injuries are common in obstetrics and gynecology and can
      cause transmission of viral diseases including hepatitis and acquired
      immunodeficiency syndrome (AIDS). Strategies to reduce the rate of needlestick
      injuries include using instruments rather than fingers to retract tissue and
      grasp needles, double gloving, using surgical staplers for skin closure, and
      substituting blunt tip surgical needles for sharp tip needles where applicable.
      Studies have shown the use of blunt tip surgical needles to be remarkably
      effective in reducing needlestick injuries. Despite recommendations by the
      American College of Surgeons that blunt tip surgical needles be used routinely,
      at least for fascial closure, and by the Occupational Safety and Health
      Administration and the National Institute for Occupational Health and Safety that
      these devices be used whenever medically appropriate, use in obstetrics and
      gynecology appears to be limited. Potential barriers to use include availability,
      the "feel" of the needle as it penetrates tissue, and habit. We suggest that
      blunt tip surgical needles have the potential to replace traditional needles for
      many obstetric and gynecologic applications. If their use is to become more
      widespread, we must focus on availability, evaluation for specific applications,
      and physician education.

PMID- 18055740
TI  - Screening and follow-up of the patient at high risk for breast cancer.
AB  - Accurately defining a patient's risk of developing breast cancer is a challenging
      endeavor. Many factors have been implicated in the causation of breast cancer and
      quantifying them is difficult. Risk stratification is performed using population
      models, such as the Gail model, as well as the patient's personal and family
      history and genetic testing. The clinician who is facile with these components
      will not only be able to identify those patients at highest risk for whom
      heightened surveillance is recommended, but also to allay the fears of the
      average-risk patient and provide them reassurance. Patients who are at very high
      risk of developing breast cancer are BRCA1 or BRCA2 gene mutation carriers, those
      with a personal history of atypical ductal hyperplasia or lobular carcinoma in
      situ with associated family history, those who have undergone therapeutic or
      similarly significant radiation exposure, and those with a history of a BRCA1 or
      BRCA2 gene mutation in the family of an untested individual. Patients with an
      elevated risk, but not in the very high risk category, are those with a family
      history of breast cancer, personal history of breast cancer, significantly dense
      breast tissue, hormone replacement therapy longer than 10 years, and a history of
      atypical ductal hyperplasia or lobular carcinoma in situ without family history
      of breast cancer. Risk-reducing strategies include chemoprevention with tamoxifen
      or raloxifene and surgical prophylaxis with bilateral prophylactic mastectomy
      and/or bilateral salpingo-oophorectomy. A high-risk surveillance regimen includes
      annual mammography, annual magnetic resonance imaging in selected individuals,
      and semiannual clinical breast exams.

PMID- 18055741
TI  - Peritoneal tuberculosis mimicking advanced-stage epithelial ovarian cancer.

PMID- 18055743
TI  - Procedure-related complications of amniocentesis and chorionic villus sampling.

PMID- 18055744
TI  - Prediction and prevention of recurrent spontaneous preterm birth.

PMID- 18055745
TI  - First- and second-trimester evaluation of risk for Down syndrome.

PMID- 18055746
TI  - Sustained relief of leiomyoma symptoms by using focused ultrasound surgery.

PMID- 18055747
TI  - Gestational age at cervical length measurement and incidence of preterm birth.

PMID- 18055748
TI  - Low-weight polypropylene mesh for anterior vaginal wall prolapse.

PMID- 18055750
TI  - ACOG Practice Bulletins. List of titles December 2007.

PMID- 18055749
TI  - ACOG Practice Bulletin No. 88, December 2007. Invasive prenatal testing for
      aneuploidy.
AB  - Prenatal diagnosis of fetal chromosomal abnormalities is the most common
      indication for invasive prenatal testing. The prevalence of chromosomal
      abnormalities in clinically recognized early pregnancy loss is greater than
      50%(1). Fetuses with aneuploidy account for 6-11% of all still births and
      neonatal deaths(2). Chromosomal abnormalities that are compatible with life but
      cause considerable morbidity occur in 0.65% of newborns, and structural
      chromosomal rearrangements that will eventually affect reproduction occur in 0.2%
      of newborns(3). Consequently, screening and diagnostic programs to detect the
      most common autosomal trisomies in liveborn infants, including Down syndrome, are
      well established. The purpose of this document is to provide clinical management
      guidelines for the prenatal diagnosis of these aneuploidies.

PMID- 18055751
TI  - ACOG Committee Opinion No. 389, December 2007. Human immunodeficiency virus.
AB  - Because human immunodeficiency virus (HIV) infection often is detected through
      prenatal and sexually transmitted disease testing, an obstetrician-gynecologist
      may be the first health professional to provide care for a woman infected with
      HIV. Universal testing with patient notification and right of refusal ("opt-out"
      testing) is recommended by most national organizations and federal agencies .
      Although opt-out and opt-in testing (but not mandatory testing) are both
      ethically acceptable, the former approach may identify more women who are
      eligible for therapy and may have public health advantages . It is unethical for
      an obstetrician-gynecologist to refuse to continue providing health care for a
      patient solely because she is , or is thought to be, seropositive for HIV. Health
      care professionals who are infected with HIV should adhere to the fundamental
      professional obligation to avoid harm to patients. Physicians who believe that
      they have been at significant risk of being infected should be tested voluntarily
      for HIV.

PMID- 18055752
TI  - ACOG Committee Opinion No. 390, December 2007. Ethical decision making in
      obstetrics and gynecology.
AB  - Physicians vary widely in their familiarity with ethical theories and methods and
      their sensitivity toward ethical issues. It is important for physicians to
      improve their skills in addressing ethical questions. Obstetrician-gynecologists
      who are familiar with the concepts of medical ethics will be better able to
      approach complex ethical situations in a clear and structured way. By considering
      the ethical frameworks involving principles, virtues, care and feminist
      perspectives, concern for community, and case precedents, they can enhance their
      ability to make ethically justifiable clinical decisions. Guidelines,consisting
      of several logical steps, are offered to aid the practitioner in analyzing and
      resolving ethical problems.

PMID- 18055753
TI  - ACOG Committee Opinion No. 391, December 2007. Health literacy.
AB  - According to the U.S. Department of Health and Human Services, health literacy is
      the degree to which individuals have the capacity to obtain, process, and
      understand basic health information and services needed to make appropriate
      health decisions. The American College of Obstetricians and Gynecologists (ACOG)
      is committed to the promotion of health literacy for all. The purpose of this
      committee opinion is to outline the complex issues surrounding health literacy
      and offer strategies for increasing health literacy in clinical practice.

PMID- 18055754
TI  - ACOG Committee Opinion No. 392, December 2007. Intrauterine device and
      adolescents.
AB  - The intrauterine device (IUD) is highly effective and widely used by women
      throughout the world. Data support the safety of IUDs for most women, including
      adolescents. This document addresses the major benefits of IUD use in
      adolescents, a population at particular risk of unintended pregnancy.

PMID- 18055755
TI  - ACOG Committee Opinion No. 393, December 2007. Newborn screening.
AB  - Newborn screening tests are designed to detect infants with specific conditions
      whose families also benefit from early diagnosis and treatment. These conditions
      include disorders of metabolism, endocrinopathies, hemoglobinopathies, hearing
      loss, and cystic fibrosis. Each state program must have a system in place for
      notification, timely follow-up, and evaluation of any infant with a positive
      screening result. Newborn screening programs have enormous public health benefits
      and have been effective in identifying newborns that can benefit from early
      treatment.

PMID- 18055756
TI  - ACOG Committee Opinion No. 394, December 2007. Cesarean delivery on maternal
      request.
AB  - Cesarean delivery on maternal request is defined as a primary cesarean delivery
      at maternal request in the absence of any medical or obstetric indication. A
      potential benefit of cesarean delivery on maternal request is decreased risk of
      hemorrhage for the mother. Potential risks of cesarean delivery on maternal
      request include a longer maternal hospital stay, an increased risk of respiratory
      problems for the baby, and greater complications in subsequent pregnancies,
      including uterine rupture and placental implantation problems. Cesarean delivery
      on maternal request should not be performed before gestational age of 39 weeks
      has been accurately determined unless there is documentation of lung maturity .
      Cesarean delivery on maternal request is not recommended for women desiring
      several children, given that the risks of placenta previa, placenta accreta, and
      the need for gravid hysterectomy increase with each cesarean delivery.

PMID- 18055757
TI  - ACOG Committee Opinions. List of titles December 2007.

PMID- 18055759
TI  - Antitumorigenic effects of peroxisome proliferator-activated receptor-gamma in
      non-small-cell lung cancer cells are mediated by suppression of cyclooxygenase-2
      via inhibition of nuclear factor-kappaB.
AB  - Pharmacological activators of peroxisome proliferator-activated receptor-gamma
      (PPARgamma) inhibit growth of non-small-cell lung cancer (NSCLC) cell lines in
      vitro and in xenograft models. Because these agents engage off-target pathways,
      we have assessed the effects of PPARgamma by overexpressing the protein in NSCLC
      cells. We reported previously that increased PPARgamma inhibits transformed
      growth and invasiveness and promotes epithelial differentiation in a panel of
      NSCLC expressing oncogenic K-Ras. These cells express high levels of
      cyclooxygenase-2 (COX-2) and produce high levels of prostaglandin E(2) (PGE(2)).
      The goal of these studies was to identify the molecular mechanisms whereby
      PPARgamma inhibits tumorigenesis. Increased PPARgamma inhibited expression of COX
      2 protein and promoter activity, resulting in decreased PGE(2) production.
      Suppression of COX-2 was mediated through increased activity of the tumor
      suppressor phosphatase and tensin homolog, leading to decreased levels of phospho
      Akt and inhibition of nuclear factor-kappaB activity. Pharmacological inhibition
      of PGE(2) production mimicked the effects of PPARgamma on epithelial
      differentiation in three-dimensional culture, and exogenous PGE(2) reversed the
      effects of increased PPARgamma activity. Transgenic mice overexpressing PPARgamma
      under the control of the surfactant protein C promoter had reduced expression of
      COX-2 in type II cells and were protected against developing lung tumors in a
      chemical carcinogenesis model. These data indicate that high levels of PGE(2) as
      a result of elevated COX-2 expression are critical for promoting lung
      tumorigenesis and that the antitumorigenic effects of PPARgamma are mediated in
      part through blocking this pathway.

PMID- 18055760
TI  - Identification of oxysterol 7alpha-hydroxylase (Cyp7b1) as a novel retinoid
      related orphan receptor alpha (RORalpha) (NR1F1) target gene and a functional
      cross-talk between RORalpha and liver X receptor (NR1H3).
AB  - The retinoid-related orphan receptors (RORs) and liver X receptors (LXRs) were
      postulated to have distinct functions. RORs play a role in tissue development and
      circadian rhythm, whereas LXRs are sterol sensors that affect lipid homeostasis.
      In this study, we revealed a novel function of RORalpha (NR1F1) in regulating the
      oxysterol 7alpha-hydroxylase (Cyp7b1), an enzyme critical for the homeostasis of
      cholesterol, bile acids, and oxysterols. The expression of Cyp7b1 gene was
      suppressed in the RORalpha null (RORalpha(sg/sg)) mice, suggesting RORalpha as a
      positive regulator of Cyp7b1. Promoter analysis established Cyp7b1 as a
      transcriptional target of RORalpha, and transfection of RORalpha induced the
      expression of endogenous Cyp7b1 in the liver. Interestingly, Cyp7b1 regulation
      seemed to be RORalpha-specific, because RORgamma had little effect. Reporter gene
      analysis showed that the activation of Cyp7b1 gene promoter by RORalpha was
      suppressed by LXRalpha (NR1H3), whereas RORalpha inhibited both the constitutive
      and ligand-dependent activities of LXRalpha. The mutual suppression between
      RORalpha and LXR was supported by the in vivo observation that loss of RORalpha
      increased the expression of selected LXR target genes, leading to hepatic
      triglyceride accumulation. Likewise, mice deficient of LXR alpha and beta
      isoforms showed activation of selected RORalpha target genes. Our results have
      revealed a novel role for RORalpha and a functional interplay between RORalpha
      and LXR in regulating endo- and xenobiotic genes, which may have broad
      implications in metabolic homeostasis.

PMID- 18055762
TI  - Lipid composition alters drug action at the nicotinic acetylcholine receptor.
AB  - We tested the hypothesis that membrane lipid composition influences drug action
      at membrane proteins by studying local anesthetic action at the nicotinic
      acetylcholine receptor (nAChR). Infrared difference spectra show that
      concentrations of tetracaine consistent with binding to the ion channel (<50
      microM) stabilize a resting-like state when the nAChR is reconstituted into
      phosphatidylcholine membranes containing the anionic lipid, phosphatidic acid,
      but have no effect on the nAChR reconstituted into membranes lacking phosphatidic
      acid, either in the presence or absence of cholesterol. Concentrations of
      tetracaine above 200 microM lead to neurotransmitter site binding in all
      membranes. In the presence of phosphatidic acid, cholesterol, or both,
      neurotransmitter site binding leads to the formation of quaternary amine-aromatic
      interactions between tetracaine and binding site tyrosine/tryptophan residues and
      the stabilization of a desensitized state. One interpretation suggested by lipid
      partitioning studies is that phosphatidic acid enhances tetracaine action at the
      channel pore by increasing the partitioning of tetracaine into the lipid bilayer,
      thereby enhancing access to the transmembrane pore. However, subtle membrane
      dependent variations in the vibrations of tyrosine and tryptophan residues, and
      agonist analog binding studies indicate that the structures of the agonist-bound
      neurotransmitter sites of the nAChR in membranes lacking both phosphatidic acid
      and cholesterol differ from the structures of the agonist-desensitized
      neurotransmitter sites in the presence of both lipids. Lipid action at the nAChR
      thus involves more than a simple modulation of the equilibrium between resting
      and desensitized states.

PMID- 18055761
TI  - Identification of the first synthetic steroidogenic factor 1 inverse agonists:
      pharmacological modulation of steroidogenic enzymes.
AB  - Steroidogenic factor SF-1, a constitutively active nuclear hormone receptor, is
      essential to the development of adrenal and gonadal glands and acts as a shaping
      factor of sexual determination and differentiation. Its effects are exerted
      primarily through the control of the synthesis of steroid hormones. The
      functional cell-based assay Receptor Selection and Amplification Technology (R
      SAT) was used to identify potent and selective SF-1 inverse agonists through the
      screening of a chemical library of drug-like small-molecule entities. Among them,
      4-(heptyloxy)phenol (AC-45594), a prototype inverse agonist lead, was used to
      show that SF-1 constitutive activity can be pharmacologically modulated by a
      synthetic ligand. In a physiological system of endocrine function, the expression
      of several reported SF-1 target genes, including SF-1 itself, was inhibited by
      treatment with AC-45594 and analogs. Thus, pharmacological modulation of SF-1 is
      critical to its function as an endocrine master regulator and has potentially
      important consequences to diseases in which SF-1 activity is critical.

PMID- 18055764
TI  - A multinomial model for identifying significant pure-tone threshold shifts.
AB  - PURPOSE: Significant threshold differences on retest for pure-tone audiometry are
      often evaluated by application of ad hoc rules, such as a shift in a pure-tone
      average or in 2 adjacent frequencies that exceeds a predefined amount. Rules that
      are so derived do not consider the probability of observing a particular
      audiogram. METHODS: A general solution for evaluating threshold differences on
      retest was developed on the basis of multinomial probabilities. The model uses
      the standard deviation of inter-test differences for 1 frequency as a parameter
      of the underlying Gaussian distribution of test results. The number of test
      frequencies, the categories of threshold change, and the probability of each
      category's occurrence are used to calculate the probability that a given pattern
      of threshold differences on retest (or 1 rarer) could occur by chance. RESULTS:
      The multinomial model was compared with 2 other methods for identifying threshold
      shifts in persons exposed to high sound pressure levels during concerts. The
      multinomial model identified the same audiograms as the ad hoc methods.
      CONCLUSION: Tables developed using a multinomial model can provide a clinical
      tool for evaluating audiograms by identifying statistically significant patterns
      of test-retest differences in hearing thresholds.

PMID- 18055765
TI  - Developmental effects of multiple looks in speech sound discrimination.
AB  - PURPOSE: The change/no-change procedure (J. E. Sussman & A. E. Carney, 1989),
      which assesses speech discrimination, has been used under the assumption that the
      number of stimulus presentations does not influence performance. Motivated by the
      tenets of the multiple looks hypothesis (N. F. Viemeister & G. H. Wakefield,
      1991), work by R. F. Holt and A. E. Carney (2005) called this assumption into
      question (at least for adults): Nonsense syllable discrimination improved with
      more stimulus presentations. This study investigates the nature of developmental
      differences and the effects of multiple stimulus presentations in the change/no
      change procedure. METHOD: Thirty normal-hearing children, ages 4.0-5.9 years,
      were tested on 3 consonant-vowel contrasts at various signal-to-noise ratios
      using combinations of 2 and 4 standard and comparison stimulus repetitions.
      RESULTS: Although performance fell below that which is predicted by the multiple
      looks hypothesis in most conditions, discrimination was enhanced with more
      stimulus repetitions for 1 speech contrast. The relative influence of standard
      and comparison stimulus repetitions varied across the speech contrasts in a
      manner different from that of adults. CONCLUSION: Despite providing no additional
      sensory information, multiple stimulus repetitions enhanced children's
      discrimination of 1 set of nonsense syllables. The results have implications for
      models of developmental speech perception and assessing speech discrimination in
      children.

PMID- 18055766
TI  - On the robustness of vocal development: an examination of infants with moderate
      to-severe hearing loss and additional risk factors.
AB  - PURPOSE: Onset of canonical babbling by 10 months of age is surprisingly robust
      in infancy, suggesting that there must be deep biological forces that keep the
      development of this key vocal capability on course. This study further evaluated
      the robustness of canonical babbling and other aspects of prelinguistic vocal
      development. METHOD: Longitudinal observation was conducted on 4 infants who were
      at risk for abnormal vocal development because of bilateral moderate-to-severe
      sensorineural hearing loss and additional risk factors for developmental delay.
      RESULTS: Two of the infants were delayed in the onset of canonical babbling and
      showed greater fluctuation in canonical babbling ratios following its onset than
      did typically developing infants. On the same measures, the remaining 2 infants
      were within normal limits, although their age of onset for canonical babbling was
      later than the mean for typically developing infants. Volubility was not notably
      different from typically developing infants. Differences from typically
      developing infants were, however, observed in proportions of various
      prelinguistic syllable types produced across time. CONCLUSION: Results provided
      further evidence of robustness of canonical babbling and indicated the need for a
      large parametric study evaluating effects of varying degrees of hearing loss and
      other risk factors on vocal development.

PMID- 18055767
TI  - Effects of training on the acoustic phonetic representation of synthetic speech.
AB  - PURPOSE: Investigate training-related changes in acoustic-phonetic representation
      of consonants produced by a text-to-speech (TTS) computer speech synthesizer.
      METHOD: Forty-eight adult listeners were trained to better recognize words
      produced by a TTS system. Nine additional untrained participants served as
      controls. Before and after training, participants were tested on consonant
      recognition and made pairwise judgments of consonant dissimilarity for subsequent
      multidimensional scaling (MDS) analysis. RESULTS: Word recognition training
      significantly improved performance on consonant identification, although
      listeners never received specific training on phoneme recognition. Data from 31
      participants showing clear evidence of learning (improvement>or=10 percentage
      points) were further investigated using MDS and analysis of confusion matrices.
      Results show that training altered listeners' treatment of particular acoustic
      cues, resulting in both increased within-class similarity and between-class
      distinctiveness. Some changes were consistent with current models of perceptual
      learning, but others were not. CONCLUSION: Training caused listeners to interpret
      the acoustic properties of synthetic speech more like those of natural speech, in
      a manner consistent with a flexible-feature model of perceptual learning. Further
      research is necessary to refine these conclusions and to investigate their
      applicability to other training-related changes in intelligibility (e.g.,
      associated with learning to better understand dysarthric speech or foreign
      accents).

PMID- 18055768
TI  - A perceptual correlate of the labial-coronal effect.
AB  - PURPOSE: Statistical studies conducted in various languages on both infants and
      adults have revealed an intersyllabic preference for initiating words with a
      labial consonant-vowel-coronal consonant sequence. Speech motor constraints have
      been proposed to explain this so-called labial-coronal effect. This study was
      designed to test for a possible perceptual correlate of the labial-coronal effect
      in French adults. METHOD: The authors examined the perceptual stabilities of
      repeatedly presented disyllabic sequences, involving either a labial-vowel
      coronal-vowel (LC) or a coronal-vowel-labial-vowel (CL) phonological structure.
      With this aim, they exploited the verbal transformation effect, which refers to
      the perceptual changes experienced while listening to a speech form cycled in
      rapid and continuous repetition. Two experiments were carried out, involving
      either voiced or unvoiced plosive consonants. RESULTS: In both experiments, a
      greater stability and attractiveness was observed for LC stimuli, which suggests
      that in a (...)LCLC(...) flow, the listener could more naturally provide a
      segmentation into LC chunks. CONCLUSION: This study demonstrates that the labial
      coronal effect also occurs in the course of online speech processing. This result
      is interpreted in relation with theories assuming a link between perception and
      action in the human speech processing system.

PMID- 18055769
TI  - Listener agreement for auditory-perceptual ratings of dysarthria.
AB  - PURPOSE: Darley, Aronson, and Brown (1969a, 1969b) detailed methods and results
      of auditory-perceptual assessment for speakers with dysarthrias of varying
      etiology. They reported adequate listener reliability for use of the rating
      system as a tool for differential diagnosis, but several more recent studies have
      raised concerns about listener reliability using this approach. METHOD: In the
      present study, the authors examined intrarater and interrater agreement for
      perceptual ratings of 47 speakers with various dysarthria types by 2 listener
      groups (inexperienced and experienced). The entire set of perceptual features
      proposed by Darley et al. was rated based on a 40-s conversational speech sample.
      RESULTS: No differences in levels of agreement were found between the listener
      groups. Agreement was within 1 scale value or better for 67% of the pairwise
      comparisons. Levels of agreement were lower when the average rating fell in the
      mid-range of the scale compared with samples that had an average rating near
      either of the scale endpoints; agreement was above chance level. No significant
      differences in agreement were found between the perceptual features. DISCUSSION:
      The levels of listener agreement that were found indicate that auditory
      perceptual ratings show promise during clinical assessment for identifying
      salient features of dysarthria for speakers with various etiologies.

PMID- 18055770
TI  - Training Japanese listeners to perceive American English vowels: influence of
      training sets.
AB  - PURPOSE: Studies on speech perception training have shown that adult 2nd language
      learners can learn to perceive non-native consonant contrasts through laboratory
      training. However, research on perception training for non-native vowels is still
      scarce, and none of the previous vowel studies trained more than 5 vowels. In the
      present study, the influence of training set sizes was investigated by training
      native Japanese listeners to identify American English (AE) vowels. METHOD:
      Twelve Japanese learners of English were trained 9 days either on 9 AE
      monophthongs (fullset training group) or on the 3 more difficult vowels (subset
      training group). Five listeners served as controls and received no training.
      Performance of listeners was assessed before and after training as well as 3
      months after training was completed. RESULTS: Results indicated that (a) fullset
      training using 9 vowels in the stimulus set improved average identification by
      25%; (b) listeners in both training groups generalized improvement to untrained
      words and tokens spoken by novel speakers; and (c) both groups maintained
      improvement after 3 months. However, the subset group never improved on untrained
      vowels. CONCLUSIONS: Training protocols for learning non-native vowels should
      present a full set of vowels and should not focus only on the more difficult
      vowels.

PMID- 18055772
TI  - Use of speaker intent and grammatical cues in fast-mapping by adolescents with
      Down syndrome.
AB  - PURPOSE: The authors asked whether adolescents with Down syndrome (DS) could fast
      map novel nouns and verbs when word learning depended on using the speaker's
      pragmatic or syntactic cues. Compared with typically developing (TD) comparison
      children, the authors predicted that syntactic cues would prove harder for the
      group with DS to use and that action verbs would be harder to fast-map than
      nouns. METHOD: Twenty participants with DS, aged 12-18 years, and 19 TD
      participants, aged 3-6 years, were matched on syntax comprehension and engaged in
      4 fast-mapping tasks. Both comprehension and production of novel words were
      assessed for each task. Through use of hierarchical regression models, hearing,
      cognition, and working memory were considered as predictors of total
      comprehension and production performance for each group. RESULTS: Both groups
      used speaker intent in fast-mapping labels to object referents but performed more
      poorly on fast-mapping verbs. Neither group appeared to use grammatical cues to
      disambiguate the intended referent. Syntax comprehension was replicated as a
      predictor of fast-mapping comprehension for the DS group. Syntax comprehension
      and chronological age were replicated as predictors of TD fast-mapping.
      CONCLUSION: Participants with DS had better recall for the object or action seen
      most recently during speaker intent tasks. They had better recall for the object
      presented first and the action presented last during grammatical cue tasks.
      Response patterns may have depended on the structure of specific task paradigms.
      Verb acquisition may be facilitated when either the action or label is familiar.

PMID- 18055771
TI  - Vowel acoustic space development in children: a synthesis of acoustic and
      anatomic data.
AB  - PURPOSE: This article integrates published acoustic data on the development of
      vowel production. Age specific data on formant frequencies are considered in the
      light of information on the development of the vocal tract (VT) to create an
      anatomic-acoustic description of the maturation of the vowel acoustic space for
      English. METHOD: Literature searches identified 14 studies reporting data on
      vowel formant frequencies. Data on corner vowels are summarized graphically to
      show age- and sex- related changes in the area and shape of the traditional vowel
      quadrilateral. CONCLUSIONS: Vowel development is expressed as follows: (a)
      establishment of a language-appropriate acoustic representation (e.g., F1-F2
      quadrilateral or F1-F2-F3 space), (b) gradual reduction in formant frequencies
      and F1-F2 area with age, (c) reduction in formant-frequency variability, (d)
      emergence of male-female differences in formant frequency by age 4 years with
      more apparent differences by 8 years, (e) jumps in formant frequency at ages
      corresponding to growth spurts of the VT, and (f) a decline of f0 after age 1
      year, with the decline being more rapid during early childhood and adolescence.
      Questions remain about optimal procedures for VT normalization and the exact
      relationship between VT growth and formant frequencies. Comments are included on
      nasalization and vocal fundamental frequency as they relate to the development of
      vowel production.

PMID- 18055773
TI  - Late language emergence at 24 months: an epidemiological study of prevalence,
      predictors, and covariates.
AB  - PURPOSE: The primary objectives of this study were to determine the prevalence of
      late language emergence (LLE) and to investigate the predictive status of
      maternal, family, and child variables. METHOD: This is a prospective cohort study
      of 1,766 epidemiologically ascertained 24-month-old singleton children. The
      framework was an ecological model of child development encompassing a wide range
      of maternal, family, and child variables. Data were obtained using a postal
      questionnaire. Item analyses of the 6-item Communication scale of the Ages and
      Stages Questionnaire (ASQ; D. Bricker & J. Squires, 1999; J. Squires & D.
      Bricker, 1993; J. Squires, D. Bricker, & L. Potter, 1997; J. Squires, L. Potter,
      & D. Bricker, 1999) yielded a composite score encompassing comprehension as well
      as production items. One SD below the mean yielded good separation of affected
      from unaffected children. Analyses of bivariate relationships with maternal,
      family, and child variables were carried out, followed by multivariate logistic
      regression to predict LLE group membership. RESULTS: 13.4% of the sample showed
      LLE via the ASQ criterion, with 19.1% using the single item of "combining words."
      Risk for LLE at 24 months was not associated with particular strata of parental
      educational levels, socioeconomic resources, parental mental health, parenting
      practices, or family functioning. Significant predictors included familial
      history of LLE, male gender, and early neurobiological growth. Covariates
      included psychosocial indicators. CONCLUSION: Results are congruent with models
      of language emergence and impairment that posit a strong role for neurobiological
      and genetic mechanisms of onset that operate across a wide variation in maternal
      and family characteristics.

PMID- 18055774
TI  - Third graders' metalinguistic skills, reading skills, and stress production in
      derived English words.
AB  - PURPOSE: This study examined relationships between 3rd graders' metalinguistic
      skills (phonological and morphological awareness), reading skills (decoding and
      word identification), and accurate stress production in derived words with stress
      changing suffixes. METHOD: Seventy-six typically developing 3rd-grade children
      (M=8;8[years;months]) participated in a battery of tests measuring general oral
      language ability, phonological and morphological awareness skills, reading
      skills, and derived word production. RESULTS: Significant positive correlations
      between stress accuracy in derived words and all other measures were found. Two
      multiple regressions were run, one with stress accuracy as the outcome variable
      and the other with decoding as the outcome variable. Metalinguistic and decoding
      skills independently accounted for a significant proportion of the variance in
      derived word stress production beyond that accounted for by age and general oral
      language ability. When decoding was the outcome variable, accurate stress
      production explained a significant amount of variance (11%) after phonological
      and morphological awareness were controlled. CONCLUSION: The relationship between
      accurate stress production and decoding appears to be strong and bidirectional.
      Possibly, the stress accuracy measure taps into another level of phonological
      awareness (i.e., morphophonological awareness), which develops later than typical
      segmental measures of phonological awareness.

PMID- 18055775
TI  - Intonation abilities of children with Williams syndrome: a preliminary
      investigation.
AB  - PURPOSE: The authors investigated expressive and receptive intonation abilities
      in children with Williams syndrome (WS) and the relation of these abilities to
      other linguistic abilities. METHOD: Fourteen children with WS, 14 typically
      developing children matched to the WS group for receptive language (LA), and 15
      typically developing children matched to the WS group for chronological age (CA)
      were compared on a range of receptive and expressive intonation tasks from the
      Profiling Elements of Prosodic Systems-Child version (PEPS-C) battery. RESULTS:
      The WS group performed similarly to the LA group on all intonation tasks apart
      from the long-item imitation task, on which the WS group scored significantly
      lower than the LA group. When compared with the CA group, the WS group was
      significantly poorer on all aspects of intonation. Whereas there were a number of
      significant correlations between the intonation and language measures in the
      control groups, in the WS group, there was only 1 significant correlation between
      a PEPS-C task and one of the language measures. CONCLUSION: As a result of this
      study, the authors concluded that children with WS have expressive and receptive
      intonation abilities as expected for their level of language comprehension and
      that intonation and other linguistic abilities in WS are not strongly related.

PMID- 18055776
TI  - Analysis and control in children with SLI.
AB  - PURPOSE: E. Bialystok and E. B. Ryan (1985) have outlined two operations,
      analysis and control, which are required for grammaticality judgments. In this
      model, analysis is involved in determining the grammaticality of a sentence, and
      control is required so that irrelevant information is ignored. This study
      examined these processes in specific language impairment (SLI). METHOD: Sixteen
      children with SLI and 20 typically developing (TD) children between 8;6
      (years;months) and 10;6 were presented with a grammatical judgment task. Analysis
      was measured by recording children's decision times in determining
      grammaticality. Control was assessed by examining accuracy for judgments made for
      semantically odd sentences. RESULTS: Relative to the TD group, it was found that
      the children with SLI took longer in judging sentences associated with the
      process of analysis. Children with SLI were also found to have more difficulty,
      in terms of accuracy, with items requiring control (e.g., semantically odd
      sentences) than did the TD group. CONCLUSION: It is argued that the longer time
      required for children with SLI to respond to semantically normal sentences
      reflects a degree of difficulty with completing analysis. The SLI group's lower
      level of accuracy on semantically odd sentences reflects a problem with a control
      and is consistent with previously reported problems with cognitive inhibition in
      SLI.

PMID- 18055777
TI  - Construct validity of the MCDI-I Receptive Vocabulary scale can be improved:
      differential item functioning between toddlers with autism spectrum disorders and
      typically developing infants.
AB  - PURPOSE: To evaluate whether the validity of the Receptive Vocabulary scale of
      the MacArthur Communicative Development Inventory for Infants (MCDI-I; L. Fenson
      et al., 1991), a parent-report measure of early vocabulary, could be improved for
      children with autism spectrum disorders (ASD) by removing items that are biased.
      METHOD: Logistic regression was used to identify biased items. Items are
      considered biased if characteristics other than those being measured by the
      instrument change the probability that a person will get an item correct.
      Participants in the current study included 272 typically developing infants
      younger than 18 months of age and 209 toddlers with ASD older than 18 months of
      age. The age difference between the 2 groups is a result of matching on total
      size of the receptive vocabulary. RESULTS: Twenty-five items were identified as
      showing large bias. CONCLUSION: Deletion of these items from the test should
      increase the degree to which the authors are measuring the size of the
      respondent's mental lexicon with the total score from the MCDI-I.

PMID- 18055778
TI  - Auditory-visual integration for speech by children with and without specific
      language impairment.
AB  - PURPOSE: It has long been known that children with specific language impairment
      (SLI) can demonstrate difficulty with auditory speech perception. However, speech
      perception can also involve the integration of both auditory and visual
      articulatory information. METHOD: Fifty-six preschool children, half with and
      half without SLI, were studied in order to examine auditory-visual integration.
      Children watched and listened to video clips of a woman speaking [bi] and [gi].
      They also listened to audio clips of [bi], [di], and [gi], produced by the same
      woman. The effect of visual input on speech perception was tested by presenting
      an auditory [bi] combined with a visually articulated [gi], which tends to alter
      the phoneme percept (the McGurk effect). RESULTS: Both groups of children
      performed at ceiling when asked to identify speech tokens in auditory-only and
      congruent auditory-visual modalities. In the incongruent auditory-visual
      condition, a stronger McGurk effect was found for the normal language group
      compared with the children with SLI. CONCLUSION: Responses by the children with
      SLI indicated less impact of visual processing on speech perception than was seen
      with their normal peers. These results demonstrate that the difficulties with
      speech perception by SLI children extend beyond the auditory-only modality to
      include auditory-visual processing as well.

PMID- 18055780
TI  - Cellular and functional optical coherence tomography of the human retina: the
      Cogan lecture.

PMID- 18055781
TI  - Simultaneous defocus integration during refractive development.
AB  - PURPOSE: To determine the effects of simultaneously presented myopic and
      hyperopic defocus on the refractive development of chicks. METHODS: A novel form
      of dual-power lens was designed. Normal chicks 7 to 8 days of age were fitted
      with a dual-power lens over one eye and a plano lens over the fellow (control)
      eye. Dual-power lenses of +20/-10, +10/-10, +5/-10, and plano/-10-D were tested,
      along with +10/-10-D lenses having differing ratios (50:50, 33:67, and 25:75) of
      surface area devoted to each power. Ocular refraction and axial ocular component
      dimensions were assessed after 6 days of lens wear, by retinoscopy and high
      frequency ultrasound, respectively. In a separate experiment designed to test the
      effect of dual-power lens wear on the refractive development of myopic eyes,
      chicks were fitted with a dual-power +10/-10-D lens for 6 days, after myopia had
      been induced by 6 days of -10-D lens wear. RESULTS: For each of the dual-power
      lenses tested, the refractive end point of the treated eye was found to lie
      between the two optical powers of the lens (but with the response weighted in
      favor of the effect of myopic defocus). Refractive development appeared to be
      modulated by the sign, dioptric magnitude, and relative contribution (relative
      contrast) of the imposed optical defocuses through an integrative mechanism.
      Chicks with myopia induced by -10-D lens wear recovered when treated with a +10/
      10-D dual-power lens. CONCLUSIONS: The chick retina can discern both the sign and
      the magnitude of optical defocus. Chick eyes were able to integrate blur cues
      from simultaneously presented images focused either side of the photoreceptors
      and to modulate their refractive development accordingly. This implies that the
      complex nature of defocus in the visual environment may play a critical role in
      the pathogenesis of myopia. The results suggest a rational method for arresting
      or reversing the development of myopia, which may be useful in the treatment of
      human myopia if the primate retina is also capable of responding to
      simultaneously presented opposing defocus cues.

PMID- 18055782
TI  - Long-term suppression of neurodegeneration in chronic experimental optic
      neuritis: antioxidant gene therapy.
AB  - PURPOSE: To test in mice with experimental autoimmune encephalomyelitis (EAE) a
      strategy designed to treat patients at risk for axonal degeneration and
      persistent visual loss from optic neuritis and multiple sclerosis. METHODS: The
      authors cloned the human extracellular superoxide dismutase (ECSOD) or catalase
      (CAT) gene into recombinant adenoassociated virus (AAV). Transgene expression was
      evaluated by immunochemistry of infected RGC-5 cells and after intravitreal
      injection of AAV-ECSOD or AAV-CAT, or both, into the right eyes of DBA/1J mice.
      Control cells and left eyes were inoculated with AAV-GFP. Animals were sensitized
      for EAE, followed by serial contrast-enhanced MRI for 6 months, and then were
      euthanatized. The effects of ECSOD and CAT modulation on the EAE optic nerve were
      gauged by computerized analysis of optic nerve volume, myelin fiber area, axonal
      cell loss, and retinal ganglion cell (RGC) loss. RESULTS: Western blot analysis
      of infected RGC-5 cells revealed that expression of ECSOD increased 15-fold and
      that of CAT increased 3.5-fold. One month after intraocular injections, transgene
      expression increased 4-fold for AAV-ECSOD and 3.3-fold for AAV-CAT. Six months
      after intraocular injections and EAE sensitization, combination therapy with
      ECSOD and catalase decreased RGC loss by 29%, optic nerve demyelination by 36%,
      axonal loss by 44%, and cellular infiltration by 34% compared with the
      contralateral control eyes inoculated with AAV-GFP. Compared with the normal
      optic nerve, it limited RGC loss to 9%. CONCLUSIONS: Viral-mediated delivery of
      antioxidant genes provides long-lasting suppression against neuronal and axonal
      loss associated with permanent visual disability in patients with optic neuritis
      and multiple sclerosis.

PMID- 18055783
TI  - Mechanism of retinoblastoma tumor cell death after focal chemotherapy, radiation,
      and vascular targeting therapy in a mouse model.
AB  - PURPOSE: To evaluate the mechanism and timing of retinal tumor cell death in the
      LH(BETA)T(AG) mouse model of retinoblastoma after treatment with vascular
      targeting therapies and conventional therapies (focal chemotherapy and
      radiation). METHODS: For vascular targeting therapy, 12- or 16-week-old mice were
      treated with a single subconjunctival injection of either anecortave acetate (300
      microg) or combretastatin A4 (1.5 mg). Eyes were analyzed at 1 day and 1 week
      after treatment. Tumor cell death was evaluated using TUNEL assays or
      immunofluorescence analysis of activated caspase 3 to detect apoptosis.
      Histopathologic analysis was performed to identify areas of necrosis. For
      conventional therapy, LH(BETA)T(AG) mice were treated with six serial
      subconjunctival injections of focally delivered carboplatin chemotherapy (100
      microg/delivery) or hyperfractionated external beam radiotherapy (EBRT; 15 Gy
      total dose). Cell death was analyzed by TUNEL assay. RESULTS: The highest levels
      of apoptotic cell death were seen 1 day after treatment in all treatment groups
      compared with vehicle controls. At 1 week after treatment, apoptotic cell death
      remained significantly elevated in the EBRT and carboplatin groups, but not after
      vessel targeting therapy. No significant necrosis was detected by histology in
      tumors of treated or of control eyes. CONCLUSIONS: Conventional therapies (focal
      carboplatin chemotherapy and EBRT) and vascular targeting agents significantly
      increase cell death through apoptosis, while not having a significant effect on
      necrosis in this murine model of retinoblastoma. These studies will aid in the
      optimization of delivery schemes of combined treatment modalities.

PMID- 18055784
TI  - Somatic ablation of the Lrat gene in the mouse retinal pigment epithelium
      drastically reduces its retinoid storage.
AB  - PURPOSE: To generate a mouse model in which the Lrat gene is selectively
      disrupted in the retinal pigment epithelium (RPE). To evaluate the effects on the
      synthesis of retinyl esters and on the expression of other proteins involved in
      the continuation of the visual cycle. METHODS: A mouse line in which part of the
      first exon of the Lrat gene has been flanked by loxP sites, was generated and
      used in the study (Lrat(L3/L3) mice). Heterozygous mice (Lrat(+/L3)) were crossed
      with mice expressing Cre-recombinase under control of the tyrosinase-related
      protein-1 (Tyrp1) promoter, which is active selectively in melanin-synthesizing
      cells such as RPE cells. Accordingly, mice obtained from these crosses should
      display an RPE-specific disruption of the Lrat gene (Lrat(rpe-/-)). In addition,
      by crossing CMV-Cre transgenic mice with Lrat(L3/L3) animals, a germline null
      Lrat knockout (Lrat(L-/L-) mice) was generated. RNA and protein expression,
      endogenous retinoid levels, and electroretinogram (ERG) analyses were performed
      on Lrat(rpe-/-) and Lrat(L-)/(L-) mice, to determine the effects of Lrat
      disruption. Retinoid levels in nonocular tissues were also analyzed for
      comparison. RESULTS: Analysis of RPE tissues from Lrat(rpe-/-) mice showed
      absence of Lrat message, lack of Lrat protein expression and consequently a
      reduced light response in ERG recordings. In addition, RPE cells from Lrat(rpe-/
      ) showed a strong reduction in their ability to synthesize all-trans retinyl
      esters, whereas Lrat activity in other tissues known to process retinol was
      comparable to control Lrat(L3/L3) animals. The Lrat(L-/L-) mice showed no
      detectable Lrat message, lack of protein expression, and barely detectable ester
      formation in RPE cells or several other relevant tissues analyzed. CONCLUSIONS:
      Three Lrat mouse lines with genetic modifications were generated. The Lrat(L-)/(L
      ) mice displayed features similar to equivalent models previously reported by
      others. The second mouse line (Lrat(rpe-/-)) displayed loss of Lrat function only
      in the RPE. The third line possesses functional Lrat in all tissues, but part of
      the Lrat coding gene was flanked by loxP sites (Lrat(L3/L3)). This feature allows
      the disruption of this gene in any tissue of choice, by intercrossing with mice
      in which Cre-recombinase expression is driven by an appropriate tissue-specific
      promoter.

PMID- 18055785
TI  - Novel retinal and cone photoreceptor transcripts revealed by human macular
      expression profiling.
AB  - PURPOSE: The macula is essential for visual acuity. It contains many more cone
      photoreceptors than does the peripheral retina. In this study, macular gene
      expression was compared with that in the rod-rich peripheral retina. METHODS: Two
      millimeter foveomacular and four-millimeter macular punches from human donor
      eyes, in addition to sections of midperipheral retina, were used to study
      differential gene expression. Multiple microarray experiments were combined with
      quantitative PCR and bioinformatic analyses. In the present study, the expression
      of both known and previously unidentified retinal genes was determined. RESULTS:
      Several macula enriched transcripts were revealed. Nuclear pore complex
      interacting protein (NPIP) and eukaryotic translation initiation factor 2alpha
      kinase (GCN2) were expressed at levels approaching that of red/green cone opsin
      in the macula. The protein products of several genes highlighted using these
      expression analyses were also localized in the retina. Both NPIP and histone
      deacetylase 9 (HDAC9) proteins were detected in cone photoreceptor outer
      segments. CONCLUSIONS: Characterizing macula enriched transcripts is an important
      stepping-stone in understanding the molecular basis for visual acuity in the
      retina. The approach also provides excellent candidates for diseases that affect
      the macula and fovea such as age-related macular degeneration (AMD). Indeed,
      several of these transcripts, such as NPIP and GCN2, have genomic loci that are
      consistent with being candidate genes for AMD.

PMID- 18055786
TI  - Late-onset cone photoreceptor degeneration induced by R172W mutation in Rds and
      partial rescue by gene supplementation.
AB  - PURPOSE: R172W is a common mutation in the human retinal degeneration slow (RDS)
      gene, associated with a late-onset dominant macular dystrophy. In this study, the
      authors characterized a mouse model that closely mimics the human phenotype and
      tested the feasibility of gene supplementation as a disease treatment strategy.
      METHODS: Transgenic mouse lines carrying the R172W mutation were generated. The
      retinal phenotype associated with this mutation in a low-expresser line (L-R172W)
      was examined, both structurally (histology with correlative immunohistochemistry)
      and functionally (electroretinography). By examining animals over time and with
      various rds genetic backgrounds, the authors evaluated the dominance of the
      defect. To assess the efficacy of gene transfer therapy as a treatment for this
      defect, a previously characterized transgenic line expressing the normal mouse
      peripherin/Rds (NMP) was crossed with a higher-expresser Rds line harboring the
      R172W mutation (H-R172W). Functional, structural, and biochemical analyses were
      used to assess rescue of the retinal disease phenotype. RESULTS: In the wild-type
      (WT) background, L-R172W mice exhibited late-onset (12-month) dominant cone
      degeneration without any apparent effect on rods. The degeneration was slightly
      accelerated (9 months) in the rds(+/-) background. L-R172W retinas did not form
      outer segments in the absence of endogenous Rds. With use of the H-R172W line on
      an rds(+/-) background for proof-of-principle genetic supplementation studies,
      the NMP transgene product rescued rod and cone functional defects and supported
      outer segment integrity up to 3 months of age, but the rescue effect did not
      persist in older (11-month) animals. CONCLUSIONS: The R172W mutation leads to
      dominant cone degeneration in the mouse model, regardless of the expression level
      of the transgene. In contrast, effects of the mutation on rods are dose
      dependent, underscoring the usefulness of the L-R172W line as a faithful model of
      the human phenotype. This model may prove helpful in future studies on the
      mechanisms of cone degeneration and for elucidating the different roles of Rds in
      rods and cones. This study provides evidence that Rds genetic supplementation can
      be used to partially rescue visual function. Although this strategy is capable of
      rescuing haploinsufficiency, it does not rescue the long-term degeneration
      associated with a gain-of-function mutation.

PMID- 18055787
TI  - Pax6p46 binds chromosomes in the pericentromeric region and induces a mitosis
      defect when overexpressed.
AB  - PURPOSE: Haploinsufficiency and overexpression of the Pax6 gene are responsible
      for defective central nervous system development. The purpose of the current work
      was to identify and characterize a new potential role for the Pax6 transcription
      factor in cellular proliferation in addition to its role at the level of gene
      expression. METHODS: Expression vectors encoding tagged Pax6p46 protein were used
      to observe directly protein localization during the cell cycle in cells lines.
      Three dimensional (3-D) fluorescence microscopy imaging was used to observe in
      vivo mitotic progression and chromosome dynamics to define the mitotic step
      affected by p46DsRed as well as to validate endogenous p46 localization on
      chromosomes in quail retinal cells. Video imaging was used to identify the
      precise moment of onset of effects related to p46 overexpression in living cells.
      A pulldown assay in HEK cells was used to identify a specific partner of p46.
      RESULTS: Pax6p46 protein in transfected cells is localized on the chromosomes,
      predominantly in a pericentromeric area, and its localization changes as mitosis
      progresses. Overexpression of p46 protein induces incomplete chromatid
      separation, resulting in defective mitosis at the onset of the anaphase. A
      physical interaction between p46 and ESPL1 was identified. CONCLUSIONS: The
      results suggest that Pax6 exerts an effect on mitosis through protein-protein
      interactions with proteins localized on chromosomes. Supported by the observation
      that p46 interacts with separase, an enzyme required for chromatid separation,
      the authors propose that this interaction is responsible for the mitosis defect
      observed in cells overexpressing Pax6.

PMID- 18055788
TI  - A key role for calpains in retinal ganglion cell death.
AB  - PURPOSE: The purpose of this study was to examine the importance of calpains in
      retinal ganglion cell (RGC) apoptosis and the protection afforded by calpain
      inhibitors against cell death. METHODS: Two different models of RGC apoptosis
      were used, namely the RGC-5 cell line after either intracellular calcium influx
      or serum withdrawal and retinal explant culture involving optic nerve axotomy.
      Flow cytometry analysis with Annexin V/PI staining was used to identify RGC-5
      cells undergoing apoptosis after treatment. TdT-mediated dUTP nick end labeling
      (TUNEL) was used to identify cells undergoing apoptosis in retinal explant
      sections under various conditions. Serial sectioning was used to isolate the cell
      population of the ganglion cell layer (GCL). Western blotting was used to
      demonstrate calpain cleavage and activity by detecting cleaved substrates.
      RESULTS: In the RGC-5 cell line, the authors reported the activation of mu
      calpain and m-calpain after serum starvation and calcium ionophore treatment,
      with concurrent cleavage of known calpain substrates. They found that the
      inhibition of calpains leads to the protection of cells from apoptosis. In the
      second model, after a serial sectioning method to isolate the cells of the
      ganglion cell layer (GCL) on a retinal explant paradigm, protein analysis
      indicated the activation of calpains after axotomy, with concomitant cleavage of
      calpain substrates. The authors found that inhibition of calpains significantly
      protected cells in the GCL from cell death. CONCLUSIONS: These results suggest
      that calpains are crucial for apoptosis in RGCs after calcium influx, serum
      starvation, and optic nerve injury.

PMID- 18055789
TI  - A common founder mutation of CERKL underlies autosomal recessive retinal
      degeneration with early macular involvement among Yemenite Jews.
AB  - PURPOSE: To investigate the genetic basis and clinical manifestations of a
      characteristic form of retinal degeneration in the Yemenite Jewish population.
      METHODS: Haplotype analysis for all known genes and loci underlying autosomal
      recessive nonsyndromic retinal degeneration was performed in a Yemenite Jewish
      family segregating autosomal recessive severe retinal degeneration. The causative
      mutation was detected by direct sequencing of the underlying gene, and its
      prevalence in additional affected and unaffected Yemenite Jews was determined.
      Patients who were homozygous for this mutation underwent ophthalmic evaluation,
      including funduscopy, electroretinography, electro-oculography, perimetry, and
      color vision testing. RESULTS: In the studied Yemenite Jewish family, we found
      evidence for linkage to the CERKL gene. Direct sequencing revealed a novel
      homozygous splice-site mutation, c.238+1G>A. An in vitro splicing assay
      demonstrated that this mutation leads to incorrect splicing. c.238+1G>A was found
      to cause retinal degeneration in six additional Yemenite Jewish families. The
      carrier frequency of this mutation in the Yemenite Jewish population is 4.4%. All
      c.238+1G>A homozygotes manifest widespread progressive impairment of rod and cone
      function with early macular involvement. CONCLUSIONS: c.238+1G>A is the second
      reported mutation of CERKL and is a prevalent founder mutation that underlies
      approximately 33% of autosomal recessive retinal degeneration cases in the
      Yemenite Jewish population. It is associated with a characteristic retinal
      degeneration phenotype with early macular involvement, concomitant progression of
      rod and cone impairment, and characteristic fundus findings. The identification
      of this mutation and phenotype will facilitate molecular diagnosis, carrier
      screening, and genetic counseling in the Yemenite Jewish population.

PMID- 18055790
TI  - Glaucoma-associated CYP1B1 mutations share similar haplotype backgrounds in POAG
      and PACG phenotypes.
AB  - PURPOSE: To understand the involvement of the CYP1B1 gene in cases of primary
      open-angle (POAG) and primary angle-closure (PACG) glaucomas and obtain the
      haplotype background of these mutations. METHODS: The entire coding region of
      CYP1B1 was screened by resequencing in 224 unrelated cases of POAG (n = 134) and
      PACG (n = 90) and 200 ethnically matched normal control subjects from Indian
      populations. Six intragenic single nucleotide polymorphisms (SNPs) in CYP1B1 (
      13T>C, R48G, A119S, V432L, D449D, and N453S) were used to generate haplotype data
      for the cases and controls and linkage disequilibrium (LD) and haplotype analysis
      were performed with Haploview software, which uses the EM (expectation
      maximization) algorithm. RESULTS: The frequency of CYP1B1 mutations was higher
      among POAG (18.6%; 95% CI, 12.9-26.1) than PACG (11.1%; 95% CI, 6.1-19.3) cases.
      There was a marked allelic heterogeneity, and the Arg368His was the most
      prevalent mutation across both the phenotypes. The spectrum of CYP1B1 mutations
      was largely similar across different POAG populations. Haplotypes generated with
      intragenic SNPs indicated the C-C-G-G-T-A to be a risk haplotype associated with
      CYP1B1 mutations in POAG (P = 0.006) and PACG (P = 0.043), similar to that
      observed in cases of primary congenital glaucoma worldwide. CONCLUSIONS: The
      results demonstrate an involvement of CYP1B1 in a proportion of POAG and PACG
      cases that should be explored further. The similar haplotype background of these
      mutations is indicative of their common origin across multiple glaucoma
      phenotypes.

PMID- 18055792
TI  - Early structural status of the eyes of healthy term neonates conceived by in
      vitro fertilization or conceived naturally.
AB  - PURPOSE: To evaluate the effects of in vitro fertilization (IVF) on early
      development of the eye in full-term healthy infants. METHODS: A case-control
      study was performed. The study sample included full-term infants born from March
      1 to August 14, 2006, in the Neonatal Department of Helen Schneider Women's
      Hospital, Rabin Medical Center. Data were collected on sex, gestational age,
      birth weight, Apgar score, head circumference, body length, and mode of
      conception (IVF/natural). A full ophthalmologic examination was performed,
      including measurement of intraocular pressure, keratometry, ultrasound biometry,
      pachymetry, and funduscopy. RESULTS: Sixty-six infants (132 eyes) were examined;
      32 were conceived by IVF, and 34 were conceived naturally. Girls accounted for
      56% of the IVF group and 44% of the natural conception group. There were no
      statistically significant differences between the groups in sex, gestational age,
      head circumference, intraocular pressure, axial length, anterior chamber depth,
      and lens thickness. The IVF infants had lower birth weight and body length than
      the infants born by natural conception (P = 0.032, t-test). Their keratometric
      and pachymetric values were also higher, but when birth weight and length were
      controlled, this difference remained statistically significant only for infants
      with a birth weight of less than 3000 g and a body length of less than 48.5 cm.
      CONCLUSIONS: IVF apparently has no effect on early development of the eyes in
      full-term infants. The steeper corneal curvature and greater central corneal
      thickness in a subset of smaller IVF infants may reflect delayed corneal
      maturation.

PMID- 18055791
TI  - A novel form of transducin-dependent retinal degeneration: accelerated retinal
      degeneration in the absence of rod transducin.
AB  - PURPOSE: Rhodopsin mutations account for approximately 25% of human autosomal
      dominant retinal degenerations. However, the molecular mechanisms by which
      rhodopsin mutations cause photoreceptor cell death are unclear. Mutations in
      genes involved in the termination of rhodopsin signaling activity have been shown
      to cause degeneration by persistent activation of the phototransduction cascade.
      This study examined whether three disease-associated rhodopsin substitutions
      Pro347Ser, Lys296Glu, and the triple mutant Val20Gly, Pro23His, Pro27Leu (VPP)
      caused degeneration by persistent transducin-mediated signaling activity.
      METHODS: Transgenic mice expressing each of the rhodopsin mutants were crossed
      onto a transducin alpha-subunit null (Tr(alpha)(-/-)) background, and the rates
      of photoreceptor degeneration were compared with those of transgenic mice on a
      wild-type background. RESULTS: Mice expressing VPP-substituted rhodopsin had the
      same severity of degeneration in the presence or absence of Tr(alpha).
      Unexpectedly, mice expressing Pro347Ser- or Lys296Glu-substituted rhodopsins
      exhibited faster degeneration on a Tr(alpha)(-/-) background. To test whether the
      absence of alpha-transducin contributed to degeneration by favoring the formation
      of stable rhodopsin/arrestin complexes, mutant Pro347Ser(+), Tr(alpha)(-/-) mice
      lacking arrestin (Arr(-/-)) were analyzed. Rhodopsin/arrestin complexes were
      found not to contribute to degeneration. CONCLUSIONS: The authors hypothesized
      that the decay of metarhodopsin to apo-opsin and free all-trans-retinaldehyde is
      faster with Pro347Ser-substituted rhodopsin than it is with wild-type rhodopsin.
      Consistent with this, the lipofuscin fluorophores A2PE, A2E, and A2PE-H(2), which
      form from retinaldehyde, were elevated in Pro347Ser transgenic mice.

PMID- 18055793
TI  - Slit lamp-simulated oblique flashlight test in the detection of narrow angles in
      Chinese eyes: the Liwan eye study.
AB  - PURPOSE: To assess a modified slit lamp-simulated oblique flashlight test in the
      identification of persons with suspected angle closure. METHODS: Standard oblique
      flashlight test (SOFT) and a modified slit lamp-simulated flashlight test (SSFT)
      were performed on participants identified as primary angle closure suspects and
      controls from a population-based study. SOFT graded the iris shadow on the nasal
      iris as shallow, medium, and deep. SSFT measured the length of iris shadow and
      corneal diameter by a slit lamp graticule eyepiece after standardizing the
      illumination parallel to the iris plane. RESULTS: SOFT yielded sensitivity and
      specificity of 76.3% and 80.7% for the detection of eyes with two or more
      quadrants of pigmented trabecular meshwork not observed on static gonioscopy.
      Proportions of subjects in the "shallow" category increased from 9.6% in Shaffer
      angle width grade 4 to 82.3% in grade 0 and were 72.1% in those with steep, 56.7%
      in those with plateau, and 13.9% in those with regular iris profiles. SSFT
      yielded 84.8% sensitivity and 76.7% specificity using a cutoff of 0.18 for the
      ratio between iris shadow length and corneal diameter. This ratio was
      monotonically associated with the axial anterior chamber depth, and it was
      significantly greater in eyes with Shaffer angle width grade lower than 2 and
      significantly less in eyes with Shaffer angle width grades 3 and 4.
      Reproducibility of SSFT was high (paired t-test; P > 0.05). CONCLUSIONS: More
      accurate measurement by controlling illumination and following a more precise
      method to measure shadow formation may improve the performance characteristics of
      this test. However, this method does not appear appropriate for community-based
      screening because of its relatively low specificity.

PMID- 18055794
TI  - Circulating hematopoietic stem cells in patients with neovascular age-related
      macular degeneration.
AB  - PURPOSE: Circulating hematopoietic stem cells (HSCs) appear to have roles in the
      formation of choroidal neovascularization (CNV) in age-related macular
      degeneration (AMD). This study was conducted to investigate whether the number or
      function of HSCs plays a role in neovascular AMD. METHODS: Eighty-one patients
      with neovascular AMD who underwent comprehensive fundus examinations every 3
      months were included. The number of CD34(+) HSCs isolated from peripheral blood
      was counted by flow cytometry. Serum cytokine levels were assessed by enzyme
      linked immunosorbent assay. To examine the function of circulating HSCs,
      mononuclear cells were cultured and then colony forming unit (CFU-EC) and
      migration were measured. RESULTS: The number of circulating CD34(+) HSCs was
      significantly increased in the patients with active CNV without major systemic
      diseases (stable: 3.8 +/- 0.3 cells/microL, active: 5.5 +/- 0.7 cells/microL,
      stable versus active: P < 0.05). The number of HSCs correlated positively with
      the erythropoietin serum level (r = 0.47, P = 0.002). Although there was no
      significant difference in the CFU-EC between the patients with CNV and the
      control subjects, a significant decrease of CFU-EC was observed in the patients
      with bilateral or larger CNV. CONCLUSIONS: The findings suggest that CD34(+) HSCs
      may be recruited from bone marrow through a signal from active CNV. Furthermore,
      HSCs may play a role in the severity of CNV.

PMID- 18055795
TI  - New tools for the evaluation of toxic ocular surface changes in the rat.
AB  - PURPOSE: To assess the usefulness of noninvasive combined technologies used to
      observe ocular surface changes in toxicology studies. METHODS: Benzalkonium
      chloride (BAC) at 0.01%, 0.1%, 0.25%, and 0.5% was applied to rat corneas for 11
      days. The eye was evaluated macroscopically from day (D)0 to D52. The cornea was
      examined with the slit lamp, a fluorescein test was performed, and a confocal
      microscope was used in vivo to calculate corneal thickness, score corneal
      epithelial and endothelial defects, and quantify corneal stromal inflammation and
      neovascularization. Conjunctival impression and brush cytology specimens were
      taken for labeling with MUC-5AC antibodies and sub-G1 peak analysis by flow
      cytometry, respectively. Histologic analyses were performed on D11. RESULTS:
      Although macroscopic and slit lamp examinations revealed signs of ocular
      irritation in the 0.25% and 0.5% BAC-treated eyes only, in vivo confocal
      microscopy revealed epithelial defects in the 0.01% and 0.1% BAC-treated corneas,
      and sub-G1 peak analyses showed increased apoptosis for all the BAC
      concentrations on D8 and D11. BAC at 0.25% and 0.5% induced increased corneal
      thickness, loss of goblet cells, reversible corneal inflammation, and persistent
      neovascularization. CONCLUSIONS: Sub-G1 peak analysis of conjunctival brushings,
      in conjunction with in vivo confocal microscopy of the cornea and immunolabeling
      of conjunctival imprints, constitutes a noninvasive, reliable, and sensitive tool
      to evaluate toxic drug-induced ocular surface damage in rats, in addition to
      standard clinical assessments and at a wide range of concentrations, including
      the lowest ones. This study is consistent with the international strategy aimed
      at reducing the use of animals and refining animal toxicologic models.

PMID- 18055796
TI  - Effects of organ culture and Optisol-GS storage on structural integrity,
      phenotypes, and apoptosis in cultured corneal epithelium.
AB  - PURPOSE: A previous report has described the use of eye bank storage of cultured
      human limbal epithelial cells (HLECs) to provide a reliable source of tissue for
      treating limbal stem cell deficiency. In the present study, conventional organ
      culture (OC) storage and Optisol-GS (Bausch & Lomb, Irvine, CA) storage of
      cultured HLECs were compared. METHODS: Three-week HLEC cultures were either organ
      cultured at 31 degrees C or 23 degrees C or stored in Optisol-GS at 5 degrees C
      in a closed container for 1 week. Morphology was studied by light microscopy and
      transmission electron microscopy, and phenotypic characterization was assessed by
      immunohistochemistry. Apoptosis was evaluated by real-time RT-PCR microarray
      analysis, caspase-3 immunohistochemistry, and terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: The ultrastructure
      was preserved at 23 degrees C, while storage at 31 degrees C and 5 degrees C was
      associated with enlarged intercellular spaces, separation of desmosomes, and
      detachment of epithelial cells. Cultured HLECs remained undifferentiated in all
      storage conditions. The expression of the antiapoptotic gene BCL2 was prominently
      upregulated in storage at 23 degrees C and 5 degrees C. Downregulation of BCL2A1,
      BIRC1, and TNF and upregulation of CARD6 in 23 degrees C and 5 degrees C storage
      conditions suggests a reduction in nuclear factor-kappaB activity. No significant
      increase in cleaved caspase-3 and TUNEL staining was observed in response to eye
      bank storage, and the labeling indices of cleaved caspase-3 (range, 0.0%-4.7%)
      and TUNEL (range, 0.0%-7.8%) were low. CONCLUSIONS: These data indicate that OC
      storage of cultured HLECs at ambient temperature is superior to OC storage at 31
      degrees C and Optisol-GS storage at 5 degrees C and that apoptosis is minimal
      after eye bank storage of cultured HLECs.

PMID- 18055797
TI  - Effect of riboflavin-UVA-induced collagen cross-linking on intraocular pressure
      measurement.
AB  - PURPOSE: Corneal collagen cross-linking (CCL) with riboflavin and ultraviolet A
      irradiation has recently been introduced for treatment of corneal ectasia. Yet a
      CCL-induced increase in corneal rigidity may interfere with intraocular pressure
      (IOP) measurements. In an investigation of the effect of CCL on the accuracy of
      IOP measurements, IOP readings before and after CCL were compared. METHODS: Ten
      human eye bank corneas were de-epithelialized and mounted on an artificial
      anterior chamber. The hydrostatically controlled reference pressure in the
      chamber was adjusted from 10 to 40 mm Hg in 5-mm Hg steps. IOP was measured by
      Goldmann applanation tonometry (GAT; Haag Streit, Konitz, Switzerland), dynamic
      contour tonometry (DCT; Pascal tonometer; Ziemer Ophthalmics, Port, Switzerland),
      and the TonoPen XL (TP; Tono-Pen XL, Medtronic, Jacksonville, FL) before and
      after CCL, which was performed with a 0.1% riboflavin solution and 30 minutes of
      UVA irradiation. RESULTS: Before CCL, GAT, and DCT readings showed an excellent
      concordance with the manometric reference pressure, whereas TP overestimated the
      true IOP. After CCL, the reliability of IOP readings decreased with all three
      tonometers. This decrease resulted in a slight overestimation of mean IOP, but
      there were also some potentially dangerous underestimations in some individual
      corneas. The mean (+/-SD) difference between IOP readings after and before CCL
      was +1.8 (3.5) mm Hg for DCT, +2.9 (6.1) mm Hg for GAT, and +3.1 (8.3) mm Hg for
      TP (P <or= 0.002 for DCT versus GAT or TP). CONCLUSIONS: In this in vitro model
      on human corneas, CCL resulted in an overestimation of true IOP by all the tested
      tonometers. Although the magnitude of this effect was small, care should be taken
      when measuring IOP with GAT after CCL, as it results in less accurate, much more
      variable IOP readings.

PMID- 18055798
TI  - Repeatability and reproducibility of pachymetric mapping with Visante anterior
      segment-optical coherence tomography.
AB  - PURPOSE: To determine the repeatability and reproducibility of central and
      peripheral corneal pachymetry mapping with anterior segment-optical coherence
      tomography (AS-OCT). METHODS: An observational cross-sectional study involving
      two groups: 27 healthy eyes and 20 eyes with keratoconus. Each subject underwent
      scanning sessions with AS-OCT to determine intraobserver repeatability,
      interobserver reproducibility, and additionally for healthy eyes, intersession
      reproducibility for different regions of the cornea up to a 10-mm diameter. Main
      outcome measures were reproducibility and repeatability coefficients, intraclass
      correlation coefficients, and coefficients of variation of the average central (0
      2 mm), pericentral (2-5 mm), transitional (5-7 mm), and peripheral (7-10 mm)
      corneal thicknesses generated by the Visante AS-OCT (Carl Zeiss Meditec, Inc.,
      Dublin, CA) pachymetric mapping protocol. RESULTS: The coefficients of
      repeatability were less than 2% in healthy subjects and less than 3% in patients
      with keratoconus. The reproducibility coefficients were less than 2% and 4% in
      healthy subjects and patients with keratoconus, respectively. There was no
      significant difference between scans obtained by different observers or during
      different visits. The intraclass correlation coefficients were greater than 0.99
      and 0.97 in healthy subjects and patients with keratoconus, respectively.
      CONCLUSIONS: With the pachymetric mapping protocol of Visante AS-OCT, these
      results suggest that central and peripheral corneal thickness measurements in
      healthy subjects and in eyes with keratoconus are repeatable and reproducible.

PMID- 18055799
TI  - Magnetic resonance imaging of innervational and extraocular muscle abnormalities
      in Duane-radial ray syndrome.
AB  - PURPOSE: The authors used magnetic resonance imaging (MRI) to study extraocular
      muscles (EOMs) and nerves in Duane-radial ray (Okihiro) syndrome (DRRS) caused by
      mutations in the transcription factor SALL4. METHODS: The authors examined four
      male and two female affected members of a pedigree previously reported to
      cosegregate DRRS and a heterozygous SALL4 mutation. Coronal T1-weighted magnetic
      resonance images of the orbits and heavily T2-weighted images in the plane of the
      cranial nerves were obtained in four subjects. MRI findings were correlated with
      motility examinations and published norms obtained using identical technique.
      RESULTS: Five of the six subjects with DRRS had radial ray abnormalities
      including thumb, radial artery, radial bone, and pectoral muscle hypoplasia.
      Three had bilateral and three had unilateral ocular involvement. Seven eyes had
      limitation of both abduction and adduction, whereas two had limitations only of
      abduction. Most affected eyes had lid fissure narrowing and retraction in
      adduction. Intraorbital and intracranial abducens nerves (CN6) were small to
      absent, particularly ipsilateral to abduction deficiency. All subjects undergoing
      MRI had normal intracranial oculomotor nerves (CN3). Optic nerve (ON) cross
      section findings were similar to normal. EOMs and pulleys were structurally
      normal in most subjects. In some affected orbits, a branch of CN3 closely
      approximated and presumably innervated the LR. CONCLUSIONS: DRRS encompasses a
      Duane syndrome phenotype, with a variable and asymmetric endophenotype including
      marked CN6 hypoplasia and probable innervation or coinnervation of the LR by CN3.
      This endophenotype is more limited than reported in DURS2-linked Duane syndrome
      (On-line Mendelian Inheritance in Man, OMIM 604356) and CFEOM1 (OMIM 135700),
      which are clinically similar congenital cranial dysinnervation disorders that
      also feature CN3 hypoplasia and more widespread EOM abnormalities.

PMID- 18055800
TI  - Unilateral deafferentation and eye position misdirect the initial vestibulo
      ocular reflex: a model-based study.
AB  - PURPOSE: Orbital eye position and vestibular sensitivity have both been
      postulated to influence vestibulo-ocular reflex (VOR) axis direction. The
      interaction of these factors in unilateral vestibular deafferentation (UVD) was
      examined. METHODS: Initial VOR direction and magnitude were examined in six
      normal human subjects and five with UVD during transient whole-body yaw at 2800
      deg/s(2). The effect of eye position was evaluated by computing the tilt angle
      ratio (TAR), the ratio of change in VOR axis orientation relative to change in
      target direction for targets 20 degrees up or down. RESULTS: Gain during the
      initial 50 ms in UVD subjects was 0.66 +/- 0.13 (mean +/- SD) during
      contralesional, and 0.30 +/- 0.16 during ipsilesional rotation, but 0.87 +/- 0.02
      in normal control subjects. In control subjects VOR axis direction was
      independent of stimulus direction. During ipsilesional rotation, subjects with
      UVD had a significant (P < 0.01) initial forward VOR axis tilt relative to
      contralesional rotation averaging 9.5 +/- 4.9 degrees , which was evident 20 ms
      after rotation. Initial TAR was 0.18 +/- 0.08 in control subjects and 0.32 +/-
      0.08 in subjects with UVD. Since Listing's Law (LL) requires 0.5 TAR, whereas a
      VOR axis perfectly aligned with head axis requires 0, the observed intermediate
      TAR implies a compromise between the two criteria. In the interval 150 to 200 ms
      after rotation onset, subjects with UVD had 0.21 +/- 0.06 TAR during
      contralesional rotation and 0.50 +/- 0.11 during ipsilesional rotation,
      suggesting late synergy between the VOR and visual pursuit. CONCLUSIONS: A vector
      based model accounts for observed axis tilt based on semicircular canal
      directional sensitivity and response saturation. Overall, the deviating effect of
      eye position on VOR axis is not influenced by UVD, but canal nonlinearity and
      geometric orientation account for the additional VOR axis error.

PMID- 18055801
TI  - Direction-of-motion detection and motion VEP asymmetries in normal children and
      children with infantile esotropia.
AB  - PURPOSE: To investigate nasal-temporal asymmetries in the detection of horizontal
      motion and in cortical motion visual evoked potential (mVEP) responses in normal
      infants and children and in patients with infantile esotropia. METHODS: Monocular
      motion-detection thresholds were obtained separately for nasalward- and
      temporalward-moving random-dot patterns in a forced-choice, preferential-looking
      paradigm. Monocular mVEP responses were obtained while subjects viewed a 6-Hz
      oscillating, 1 cyc/deg vertical sine-wave grating. Nasal-temporal mVEP asymmetry
      was investigated with two measures from each subject: asymmetric indices (AIs)
      and interocular phase differences. Performance was compared in 33 visits of 28
      normal subjects and 73 visits of 54 patients with infantile esotropia, ranging in
      age from 2 months to 5 years. RESULTS: At 3 to 5 months of age, both normal
      infants and patients with infantile esotropia had robust nasal-temporal
      asymmetries in motion-detection and mVEP measures. By 2 years of age, measures in
      all normal subjects were symmetric, as they were in patients successfully treated
      with glasses or alignment surgery, whereas patients who had not yet undergone
      alignment surgery, regardless of surgery status, had highly asymmetric mVEP
      responses and motion-detection thresholds. CONCLUSIONS: Young normal and
      esotropic infants exhibited nasal-temporal asymmetries in both motion detection
      and mVEP. These asymmetries similarly disappeared over time in normal infants and
      in patients with esotropia who had received successful, timely correction of
      misalignment. Although the initial capacity for motion processing is normal in
      the youngest patients with untreated esotropia at 5 months, cumulative abnormal
      binocular experience in these patients may disrupt motion mechanisms.

PMID- 18055802
TI  - Second-order optic flow deficits in amblyopia.
AB  - PURPOSE: Amblyopic observers show deficits for global motion discrimination that
      cannot be accounted for by their contrast sensitivity impairment. The processing
      of first- and second-order translational global motion is deficient, as is the
      processing of first-order optic flow, suggesting that cortical function in
      extrastriate areas is impaired. The authors sought to determine whether amblyopes
      show impairment in the processing of optic flow defined by second-order motion,
      whether these deficits are comparable in the two eyes, and whether these deficits
      are correlated with first-order deficits. METHODS: Eight amblyopic subjects
      (three strabismic, three strabismic-anisometropic, one anisometropic, one
      deprivation; mean age, 29 years) were tested. The authors used random dot
      kinematograms in which the dots were luminance or contrast modulations of
      background noise. The global pattern of dot motion within the stimulus area was
      translational, radial, or rotational. Coherence thresholds for direction
      discrimination were obtained across a range of dot modulation depths, allowing
      the separation of contrast and motion deficits. RESULTS: The present study showed
      that deficits in second-order optic flow processing were equivalent to those for
      first-order stimuli and that these were unrelated to the extent of the amblyopic
      contrast sensitivity deficit and were comparable in both eyes. Radial optic flow
      was more affected than rotational optic flow. CONCLUSIONS: Global motion
      impairment appeared to have a high-level binocular locus and was independent of
      the depth of the contrast deficit. Results also support the idea that global
      motion and optic flow processing are form-cue invariant.

PMID- 18055803
TI  - Changes in gene expression in experimental glaucoma and optic nerve transection:
      the equilibrium between protective and detrimental mechanisms.
AB  - PURPOSE: The authors studied retinal gene expression changes in rats after
      experimental intraocular pressure elevation and optic nerve transection to
      elucidate molecular mechanisms of retinal ganglion cell (RGC) death. METHODS:
      Translimbal laser photocoagulation was used to induce unilateral IOP elevation in
      41 albino Wistar rats. In 38 additional animals, unilateral transection of the
      optic nerve was performed. Retinas were harvested 1 day, 3 days, 1 week, 2 weeks,
      4 weeks, and 8 weeks after each treatment, and total RNA was isolated. Pooled RNA
      from each time point was analyzed with rat genome arrays. Array results were
      confirmed by real-time PCR, and localization studies were performed using in situ
      hybridization for select genes. RESULTS: Genes that were upregulated in glaucoma,
      but not after transection, included Cyclin D2, Stat1, Stat3, c-Fos, Junb, Anxa1,
      Anxa 3, and CCAAT/enhancer binding protein (Cebp-delta). In glaucoma and
      transection models, the upregulation of c-Jun, Activating transcription factor 3,
      Heat shock protein 27, and Timp1 were observed. Comparisons among microarray
      databases were performed between our data and reports of retinal and optic nerve
      injury models in mice, rats, and monkeys. CONCLUSIONS: Gene expression changes
      specific to experimental glaucoma injury were identified. The present analysis
      supports the importance of neuroinflammation and the participation of the tumor
      necrosis factor alpha signaling pathway in glaucoma injury. The alterations
      observed include processes that are both protective of and detrimental to the
      survival of RGCs.

PMID- 18055804
TI  - Potential role of Rho-associated protein kinase inhibitor Y-27632 in glaucoma
      filtration surgery.
AB  - PURPOSE: To investigate the role of Y-27632, a specific inhibitor of Rho
      associated protein kinase (ROCK) in regulating human Tenon fibroblast (HTF)
      activities including proliferation, adhesion, contraction, migratory response,
      and myofibroblast transdifferentiation. Effects of Y-27632 on prevention of
      postoperative scar formation were also examined in a rabbit model of glaucoma
      filtration surgery. METHODS: After treatment of HTFs with Y-27632, cell toxicity,
      proliferation, migration, adhesion, and contraction were studied. The
      cytoskeleton and alpha-smooth muscle actin (alpha-SMA) expression were examined
      via immunohistochemistry. In vivo studies in Japanese white rabbits consisted of
      a full-thickness sclerostomy followed in the 7-day postoperative period by
      topical application of Y-27632. Intraocular pressure, morphologic changes in bleb
      features, and histology of surgical sites were evaluated. RESULTS: Y-27632 had no
      direct toxicity or significant effects on cell proliferation of HTF. The cell
      adhesion assay showed that Y-27632 promoted adhesiveness to both fibronectin and
      collagen type I. Use of Y-27632 significantly inhibited collagen gel contraction
      and alpha-SMA expression in HTFs. Y-27632 also increased HTF motility. In vivo, Y
      27632 inhibited wound healing and fibroproliferation after filtration surgery and
      significantly improved surgical outcome compared with the vehicle. Histologic
      examination revealed that blebs in the Y-27632-treated group differed from those
      in the vehicle-treated group in that they lacked significant collagen deposition
      in the sclerostomy area. CONCLUSIONS: Y-27632 had profound effects on activities
      of HTFs and was effective in preventing fibroproliferation and scar formation in
      a rabbit model of glaucoma surgery. A ROCK inhibitor may be an effective anti
      scarring agent after glaucoma filtering surgery.

PMID- 18055805
TI  - Impaired cytoprotective mechanisms in eyes with pseudoexfoliation
      syndrome/glaucoma.
AB  - PURPOSE: Evidence suggests that chronically increased stress conditions in the
      anterior eye segment constitute major mechanisms involved in the pathobiology of
      pseudoexfoliation (PEX) syndrome. The expression of stress-related genes in eyes
      from patients with and without PEX syndrome/glaucoma was investigated to
      determine whether PEX syndrome is associated with an altered cellular stress
      response. METHODS: cDNA array hybridization, quantitative real-time PCR, Western
      blot analysis, and immunohistochemistry were applied to analyze the mRNA and
      protein expression of stress-related genes in anterior segment tissues of PEX
      eyes, with and without glaucoma, and to compare them with normal and glaucomatous
      control eyes. RESULTS: Hybridization of cDNA arrays identified a set of stress
      related candidate genes for differential expression in PEX syndrome/glaucoma, of
      which 10 were confirmed by real-time PCR in ciliary processes and iris tissue.
      The expression of MAPKp38, heat shock proteins (HSP40, HSP60), and superoxide
      dismutase (SOD2) was increased up to threefold in PEX specimens. In contrast, a
      large set of cytoprotective gene products, including antioxidant defense enzymes
      (glutathione S-transferases mGST1 and GSTT1), ubiquitin-conjugating enzymes
      (UBE2A, UBE2B), the DNA repair protein MLH1, and the stress-inducible
      transcription factor GADD153, were found to be consistently downregulated up to
      threefold in PEX specimens on both the mRNA and protein levels. CONCLUSIONS: The
      present findings provide evidence of alterations in cytoprotective mechanisms
      including antioxidant defense, proteasome function, endoplasmic reticulum-related
      stress response, and DNA repair in anterior segment tissues of PEX eyes. The
      resultant enhanced sensitivity and vulnerability to cellular stress conditions
      may therefore be one contributing factor in the pathobiology of PEX syndrome.

PMID- 18055806
TI  - Upregulation of EphB2 and ephrin-B2 at the optic nerve head of DBA/2J
      glaucomatous mice coincides with axon loss.
AB  - PURPOSE: To identify genes with upregulated expression at the optic nerve head
      (ONH) that coincides with retinal ganglion cell (RGC) axon loss in glaucomatous
      DBA/2J mice. To further demonstrate that the proteins encoded by these genes bind
      to RGC axons and influence fundamental axon physiology. METHODS: In situ
      hybridization and cell-type-specific immunolabeling were performed on ONH
      sections from DBA/2J mice (3 to 11 months old) and C57Bl/6NCrl mice (10 months
      old). EphB2-Fc and ephrin-B2-Fc chimeric proteins were applied to adult RGC axons
      in vitro and in vivo at the ONH to demonstrate protein binding on axons. EphB2-Fc
      or control Fc protein was applied in a bath or locally to axons preloaded with
      the calcium indicator Fluo-4-AM, and changes in intra-axonal calcium were
      determined. RESULTS: EphB2 and ephrin-B2 were specifically upregulated at the ONH
      of DBA/2J mice starting at 9 months of age, but not in age-matched C57Bl/6NCrl
      mice or in DBA/2J animals that did not have axon loss. EphA4 was also present at
      the ONH, but no difference in expression was detected between unaffected and
      affected animals. EphB2 was expressed by F4/80(+), MOMA2(+), ED1(-) macrophage
      like cells, ephrin-B2 was expressed by Iba-1(+) microglia and GFAP(+) astrocytes,
      whereas EphA4 was expressed by GFAP(+) astrocytes. EphB2-Fc and ephrin-B2-Fc
      protein bound to RGC axons in culture and to ONH RGC axons in vivo. Adult RGC
      axons in vitro elevated intra-axonal calcium in response to EphB2-Fc but not to
      control Fc protein. CONCLUSIONS: The expression of EphB2 and ephrin-B2 is
      upregulated at the ONH of glaucomatous DBA/2J mice coinciding with RGC axon loss.
      The direct binding of EphB2 and ephrin-B2 on adult RGC axons at the ONH and the
      ability of EphB2 to elevate intra-axonal calcium indicate that these proteins may
      affect RGC axon physiology in the setting of glaucoma and thus affect the
      development or progression of the disease.

PMID- 18055808
TI  - Nuclear and mitochondrial analysis of patients with primary angle-closure
      glaucoma.
AB  - PURPOSE: Certain types of glaucoma are linked to nuclear genetic mutations or to
      mitochondrial disturbances. In this study, patients with primary angle-closure
      glaucoma (PACG) were examined for mutations in nuclear genes reported to be
      associated with glaucoma and for possible mitochondrial abnormalities. METHODS:
      In patients with PACG, the nuclear genes MYOC, OPTN, CYP1B1, WDR36, OPA1, and
      OPA3 were sequenced, the entire mitochondrial (mt)DNA coding region was
      sequenced, relative mtDNA content was measured, and mitochondrial respiratory
      activity (MRA) was assessed. RESULTS: No novel or previously reported mutations
      were present in the nuclear genes MYOC, OPTN, CYP1B1, WDR36, OPA1, and OPA3 in 29
      patients with PACG. Four (13.8%) patients had potentially pathologic mtDNA
      nucleotide changes not found in control subjects. The patients with PACG did not
      differ significantly from the control subjects in relative mitochondrial content
      and had only a small decrease in MRA (2.4%) of indeterminate significance.
      CONCLUSIONS: These Middle Eastern patients with PACG had no mutations in nuclear
      genes associated with other types of glaucoma or inherited optic neuropathies.
      Mitochondrial abnormalities were minimal, and the overall pattern of those
      abnormalities was distinctly different from that of Leber hereditary optic
      neuropathy, nonarteritic ischemic optic neuropathy, primary open-angle glaucoma,
      and optic neuritis. These results are consistent with the hypothesis that
      anatomic factors may be more important determinants for PACG than the genetic and
      mitochondrial factors evaluated here.

PMID- 18055807
TI  - Assessing visual field clustering schemes using machine learning classifiers in
      standard perimetry.
AB  - PURPOSE: To compare machine learning classifiers trained on three clustering
      schemes to determine whether distinguishing healthy eyes from those with
      glaucomatous optic neuropathy (GON) can be optimized by training with clustered
      data. METHODS: Two machine learning classifiers-quadratic discriminant analysis
      (QDA) and support vector machines with Gaussian kernel (SVMg)-were trained
      separately using standard perimetry data from the Diagnostic Innovations in
      Glaucoma Study (DIGS), clustered using three clustering schemes on a training
      data set (123 eyes/123 glaucoma patients with GON; 135 eyes/135 normal control
      subjects). Trained classifiers were then applied to an independent data set
      containing 69 eyes of 69 glaucoma patients with early visual field loss and 83
      eyes of 83 normal control subjects. Two control conditions were included:
      unclustered data and a random assignment of locations to clusters. RESULTS: Areas
      under the receiver operating characteristic (ROC) curve ranged from 0.85 (SVMg,
      thresholds clustered by Glaucoma Hemifield Test sectors) to 0.92 (QDA, thresholds
      clustered by Garway-Heath mapping) for the training data set. Use of clustered
      data showed no significant optimization of sensitivity over use of unclustered
      data, and no single clustering method resulted in significantly higher
      performance in the independent data set. Sensitivities tended to be higher with
      QDA than with SVMg, regardless of specificity cutoff and clustering METHOD: 
      CONCLUSIONS: QDA performed better with the early glaucoma data set than did the
      SVMg. Clustering may be advantageous when data-dimension reduction is needed-for
      example, when combining field results with other high-dimensional data (e.g.,
      structural imaging data)-but it is not necessary for visual field data alone.

PMID- 18055809
TI  - Effect of immunization with the mannose-induced Acanthamoeba protein and
      Acanthamoeba plasminogen activator in mitigating Acanthamoeba keratitis.
AB  - PURPOSE: The mannose-induced cytopathic protein (MIP-133) and Acanthamoeba
      plasminogen activator (aPA) play key roles in the pathogenesis of Acanthamoeba
      keratitis by inducing a cytopathic effect on the corneal epithelial and stromal
      cells and by production of proteolytic enzymes that facilitate the invasion of
      trophozoites through the basement membrane. The goal of the present study was to
      gain insight into the pathogenicity of Acanthamoeba infection as well as to
      determine whether oral immunization with aPA and MIP-133 produce an additive
      protection against Acanthamoeba keratitis. METHODS: MIP-133 and aPA were isolated
      by chromatography. The purity of the concentrated MIP-133 and aPA was confirmed
      by SDS-PAGE and fibrinolytic activity, respectively. aPA activity of Acanthamoeba
      cultures was quantitated by radial diffusion in fibrin-agarose gel. The capacity
      of aPA and MIP-133 to induce cytolysis of corneal epithelial cells was tested in
      vitro. Chinese hamsters were orally immunized with four weekly doses of aPA or
      MIP-133 conjugated with cholera toxin. The animals were immunized before
      infection to determine the prophylactic effect of oral immunization. The
      therapeutic effect of oral immunization with aPA and MIP-133 was determined after
      corneal infection had been established. The animals were then infected via
      Acanthamoeba castellanii-laden contact lenses. RESULTS: aPA was characterized in
      pathogenic and nonpathogenic strains of Acanthamoeba spp. Oral immunization with
      MIP-133 before and after infection with Acanthamoeba significantly reduced the
      severity of corneal infection which includes infiltration and ulceration (P <
      0.05) and shortened the duration of the disease. Immunization with aPA alone did
      not significantly affect the course of disease (P > 0.05). CONCLUSIONS: These
      data suggest that once trophozoites invade the cornea, MIP-133 production is
      necessary to initiate corneal disease and plays an important role in the
      subsequent steps of the pathogenic cascade of Acanthamoeba keratitis.

PMID- 18055810
TI  - Macrophages are important determinants of acute ocular HSV-1 infection in
      immunized mice.
AB  - PURPOSE: To determine the effect of macrophage depletion on herpes simplex virus
      type (HAV)-1 replication in the eye and on the establishment of latency in
      trigeminal ganglia (TG) of immunized and ocularly infected mice. METHODS: BALB/c
      mice were immunized with five HSV-1 glycoprotein DNA genes or were sham
      immunized. The virulent HSV-1 strain KOS was used as a positive vaccine control.
      Immunized mice were depleted of their macrophages by dichloromethylene
      diphosphonate (Cl(2)MDP) injection. After ocular infection with the HSV-1 strain
      McKrae, virus replication in the eye, blepharitis, corneal scarring, and
      dermatitis were determined. Finally, the copy numbers of latency-associated
      transcript (LAT) and CD4(+) and CD8(+) T-cell transcripts in the TGs of surviving
      mice 30 days after infection were determined by RT-PCR. RESULTS: Depletion of
      macrophages in immunized mice increased HSV-1 replication in the eye of infected
      mice between days 1 and 5 after ocular infection. Depletion of macrophages did
      not alter the HSV-1-induced death or corneal scarring in immunized mice.
      Macrophage depletion, however, resulted in increased blepharitis in immunized
      mice. Finally, macrophage depletion had no effect on the establishment of latency
      in immunized mice, as the TGs from both depleted and mock-depleted mice were
      negative for the presence of the LAT transcript. CONCLUSIONS: In immunized mice
      during primary HSV-1 ocular infection, macrophages play an important role in
      vaccine efficacy against HSV-1 replication in the eye and blepharitis in infected
      mice. During the latent stage of HSV-1 infection, however, macrophage depletion
      failed to have any observable effect on HSV-1 latency in the TGs of infected
      mice.

PMID- 18055811
TI  - Ocular pathogen or commensal: a PCR-based study of surface bacterial flora in
      normal and dry eyes.
AB  - PURPOSE: To compare the bacterial population of the ocular surface of normal and
      dry eye subjects using conventional culture and 16S rDNA PCR. METHODS: Ninety-one
      subjects were classified as normal (n = 57) or dry eye (n = 34) by using tear
      break-up time, McMonnies survey, goblet cell density, and meibomian gland
      assessment. Conventional bacterial culture and broad-range 16S rDNA PCR, cloning,
      and DNA sequencing were used for bacterial identification. Repeated sampling was
      performed in a subset of subjects over a 3-month period. The association between
      goblet cell loss and bacterial counts in a subgroup of subjects was assessed.
      RESULTS: Most of the bacteria identified by culture were coagulase negative
      staphylococci, whereas molecular methods demonstrated a considerable number of
      additional bacteria. Atypical ocular surface bacteria including Rhodococcus
      erythropolis, Klebsiella oxytoca, and Erwinia sp., were identified in cases of
      overt inflammation and, surprisingly, on the normal ocular surface. The same
      bacteria remained on the ocular surface after repeated sampling. Increased
      bacterial flora was associated with reduced goblet cell density. CONCLUSIONS:
      Molecular analysis revealed a diverse ocular surface bacterial population. In
      addition to the normal flora, various potentially pathogenic bacteria were
      identified. The detection of known pathogens in both normal and dry eyes, with
      minimal signs of infection, presents a diagnostic dilemma. It remains unknown
      whether their presence is associated with inflammation and reduced goblet cell
      density or whether they adversely affect the ocular surface predisposing it to
      abnormal microbial colonization. In the absence of overt clinical infection, it
      is unknown whether such results should prompt intervention with therapy.

PMID- 18055813
TI  - Optimal lens epithelial cell proliferation is dependent on the connexin isoform
      providing gap junctional coupling.
AB  - PURPOSE: Gap junctions between epithelial cells are essential for normal lens
      growth. In mice, knockout of Cx50 or targeted replacement of Cx50 with Cx46
      (knockin) caused smaller lenses because of decreased epithelial cell
      proliferation. However, it remains unclear whether Cx50 functionally contributes
      to lens epithelial coupling during maximal proliferation on postnatal day 2 (P2)
      and P3. To determine which connexins functionally contribute to epithelial cell
      coupling and proliferation, junctional coupling from epithelial cells of wild
      type and knockin mice was examined. METHODS: Epithelial cells were isolated from
      wild-type or knockin mice at different developmental ages. Junctional currents
      were measured by dual whole cell voltage clamp. Cell proliferation was assayed by
      BrdU incorporation. Connexins were immunolocalized using specific antibodies.
      RESULTS: Junctional currents between lens epithelial cells exhibited a
      developmentally regulated sensitivity to quinine, a drug that blocks Cx50 gap
      junctions, but not Cx43 or Cx46. Single-channel currents had a unitary
      conductance of 210 pS, typical of Cx50. Immunocytochemical staining showed Cx43
      and Cx50 were abundantly expressed in wild-type cells, and Cx46 replaced Cx50 in
      knockin cells. A correlation between functional activity of Cx50 and maximal
      proliferation was also found. In epithelial cells from P3 wild-type mice, there
      was a high density of BrdU-labeled nuclei in both the central epithelium and the
      equatorial epithelium, and 60% or more of total coupling was provided by Cx50. In
      older cells, proliferation was greatly reduced, and the contribution of Cx50 to
      total coupling was progressively reduced (45% or less on P12; 25% or less on
      P28). Coupling between epithelial cells of Cx46 knockin mice was similar in
      magnitude to that of wild-type mice but had pharmacologic and biophysical
      characteristics of Cx46. This functional replacement of Cx50 with Cx46 was
      correlated with 71% and 13% reductions in BrdU-labeled cells in the P3 central
      epithelium and equatorial epithelium, respectively. CONCLUSIONS: These results
      reconcile previous genetic studies showing that Cx50 influences epithelial cell
      proliferation, with numerous studies suggesting that Cx43 was the principal
      epithelial cell connexin. They further show that the contribution of Cx50 is
      highest during peak postnatal proliferation but progressively declines with age
      thereafter.

PMID- 18055812
TI  - Autoimmune Th2-mediated dacryoadenitis in MRL/MpJ mice becomes Th1-mediated in IL
      4 deficient MRL/MpJ mice.
AB  - PURPOSE: MRL/MpJ mice of substrains MRL/MpJ-fas(+)/fas(+) (MRL/+) and MRL/MpJ
      fas(lpr)/fas(lpr) (MRL/lpr) spontaneously develop autoimmune dacryoadenitis and
      sialadenitis and are a model for the human disorder Sjogren syndrome. The
      dacryoadenitis in both substrains appears to be Th2 in nature, with little IFN
      gamma and substantial IL-4 at the site of lacrimal gland inflammation. METHODS:
      MRL/MpJ mice with a defective IL-4 gene-both MRL/+-IL-4(tm)/IL-4(tm) (MRL/+/IL
      4(tm)) and MRL/lpr-IL-4(tm)/IL-4(tm) (MRL/lpr-IL-4(tm))-that resulted in a loss
      of IL-4 production were bred and evaluated for dacryoadenitis. RESULTS: MRL/+/IL
      4(tm) and MRL/lpr/IL-4(tm) mice developed dacryoadenitis of similar onset,
      appearance, and severity as found in MRL/MpJ mice with an intact IL-4 gene.
      Immunohistochemistry examination revealed a substantially greater number of
      inflammatory cells staining for IFN-gamma than for IL-13 in the dacryoadenitis of
      IL-4-deficient MRL/MpJ mice (MRL/+/IL-4(tm), 66% vs. 0.8%, P = 0.001; MRL/lpr/IL
      4(tm), 67% vs. 1.2%, P = 0.002). Real-time PCR demonstrated greater amounts of
      IFN-gamma than IL-13 mRNA relative transcripts in lacrimal glands of MRL/lpr/IL
      4(tm) mice (mean difference, 28.6; P = 0.035). Greater CD86 (B7-2) than CD80 (B7
      1) expression was present in MRL/+/IL-4(tm) mice (11% vs. 3%, P = 0.003) and
      MRL/lpr/IL-4(tm) mice (10% vs. 3%, P = 0.002). CONCLUSIONS: These results suggest
      that a Th2 autoimmune process can be converted to a Th1 process in the absence of
      IL-4.

PMID- 18055814
TI  - DNase IIbeta distribution and activity in the mouse lens.
AB  - PURPOSE: To map the cellular and subcellular distribution of DNase IIbeta
      activity in the mouse lens. METHODS: DNase IIbeta-specific activity was
      determined by assaying lens lysates prepared from wild-type or DNase IIbeta-null
      mice. Regional nuclease activity was determined by microdissection of lens
      samples or a tissue-imprinting assay. Subcellular distribution was determined by
      density-gradient ultracentrifugation. RESULTS: DNase IIbeta transcripts increased
      200-fold in abundance during fiber cell formation, and DNase IIbeta activity
      accounted for approximately 50% of the acid nuclease activity in the cortical
      fiber cells. Examination of lenses from DNase IIbeta-null mice confirmed that the
      enzyme was required for denucleation. In wild-type lenses, nuclei were TUNEL
      positive before denucleation, indicating that 3'-OH DNA ends had accumulated.
      However, DNase IIbeta-mediated scission generates 3'-PO(4)(-) DNA ends only. This
      paradoxical finding was explained by the presence of phosphatases that converted
      the 3'-PO(4)(-) ends produced by DNase IIbeta into 3'-OH ends. DNase IIbeta
      activity was strongest early in differentiation, where it was associated with the
      lysosomal fraction. Later, an increasing proportion of DNase IIbeta activity was
      found in the cytosol. CONCLUSIONS: DNase IIbeta activity correlated with and was
      necessary for fiber denucleation and was most likely contained initially within
      fiber cell lysosomes before release into the cytoplasm.

PMID- 18055815
TI  - The effect of topical diclofenac on choroidal blood flow in early postoperative
      pseudophakias with regard to cystoid macular edema formation.
AB  - PURPOSE: To study the chronological change in choroidal blood flow (ChBFlow),
      disruption of the blood-aqueous barrier, and incidence of cystoid macular edema
      (CME) in early postoperative pseudophakic eyes, as well as the effect of
      nonsteroidal anti-inflammatory drug (NSAID) eye drops on these phenomena.
      METHODS: Fifty patients who underwent phacoemulsification and foldable
      intraocular lens (IOL) implantation were randomized to receive either topical
      diclofenac or fluorometholone for 5 postoperative weeks. An additional 20
      subjects, with long-standing pseudophakia served as the control. The blood
      aqueous barrier was examined by laser flarimetry and choroidal blood velocity
      (ChBVel), volume (ChBVol), and ChBFlow by laser Doppler flowmetry (LDF) at 2 days
      and 1, 2, and 5 weeks after surgery. The incidence and severity of CME were
      evaluated by fluorescein angiography at 2 and 5 weeks after surgery. RESULTS:
      Compared with patients taking diclofenac, those receiving fluorometholone showed
      significantly reduced ChBVol at 2 weeks (0.38 +/- 0.08 vs. 0.32 +/- 0.07, P =
      0.022) and ChBFlow at 1 (11.01 +/- 1.74 vs. 9.35 +/- 1.51, P = 0.003) and 2
      (11.15 +/- 1.43 vs. 8.47 +/- 1.27, P = 0.000) weeks after surgery, as well as a
      significantly elevated amount of anterior flare at 1 (8.9 +/- 2.2 vs. 24.4 +/-
      18.9, P = 0.001) and 2 (9.2 +/- 3.5 vs. 16.7 +/- 12.3, P = 0.025) weeks after
      surgery. The ChBVol and ChBFlow in the fluorometholone group, however, returned
      to normal and was not different from the diclofenac group at 5 weeks after
      surgery. The incidence of fluorescein angiographic CME trended to be higher (P =
      0.08) at 2 weeks and was significantly higher (P = 0.001) at 5 weeks after
      surgery in eyes with fluoromethalone than with diclofenac. CONCLUSIONS: Reduction
      of ChBFlow, disruption of the blood-aqueous barrier, and incidence of CME in
      early postsurgical pseudophakic eyes were more effectively prevented
      chronologically in eyes treated with diclofenac than in those treated with
      fluorometholone.

PMID- 18055816
TI  - Mutation screening of 299 Spanish families with retinal dystrophies by Leber
      congenital amaurosis genotyping microarray.
AB  - PURPOSE: Leber Congenital Amaurosis (LCA) is one of the most severe inherited
      retinal dystrophies with the earliest age of onset. This study was a mutational
      analysis of eight genes (AIPL1, CRB1, CRX, GUCY2D, RPE65, RPGRIP1, MERTK, and
      LRAT) in 299 unrelated Spanish families, containing 42 patients with initial
      diagnosis of LCA: 107 with early-onset autosomal recessive retinitis pigmentosa
      (ARRP; onset <10 years of age) and 150 with non-early-onset ARRP (onset, >10
      years of age). METHODS: Samples were studied by using a genotyping microarray
      (Asper Biotech, Ltd., Tartu, Estonia) followed by a family study in cases with
      potential digenism/triallelism. RESULTS: The frequencies of alleles carrying
      disease-causing mutations found in the authors'cohort using the chip were 23.8%
      (20/84) for LCA with 13 families carrying mutations, 6.1% (13/214) for early
      onset ARRP with 12 families carrying mutations, and 4.3% (13/300) for non-early
      onset ARRP with 12 families carrying mutations. CRB1 was the most frequently
      found mutated gene in affected Spanish families. Five families with anticipated
      digenism or triallelism were further studied in depth. Digenism could be
      discarded in all these cases; however, triallelism could not be ruled out.
      CONCLUSIONS: CRB1 is the main gene responsible for LCA in the Spanish population.
      Sequence changes p.Asp1114Gly (RPGRIP1), p.Pro701Ser (GUCY2D), and p.Tyr134Phe
      (AIPL1) were found at similar frequencies in patients and control subjects. The
      authors therefore suggest that these changes be considered as polymorphism or
      modifier alleles, rather than as disease-causing mutations. The LCA microarray is
      a quick and reasonably low-cost first step in the molecular diagnosis of LCA. The
      diagnosis should be completed by conventional laboratory analysis as a second
      step. This stepwise proceeding permits detection of novel disease-causing
      mutations and identification of cases involving potential digenism/triallelism.
      Previous accurate ophthalmic diagnosis was found to be indispensable.

PMID- 18055817
TI  - MMP-14 and TIMP-2 overexpression protects against hydroquinone-induced oxidant
      injury in RPE: implications for extracellular matrix turnover.
AB  - PURPOSE: To investigate whether overexpression of MMP-14 and/or TIMP-2 would
      overcome the effect of nonlethal oxidant injury with hydroquinone (HQ) on MMP-2
      activity. METHODS: Human MMP-14 and TIMP2 cDNA were cloned into a mammalian
      expression vector. Transient transfections were performed on human ARPE-19 cells.
      The cells were incubated 48 hours after transfection with a nonlethal dose of HQ
      for either 6 or 18 hours and then were collected for protein determination or RNA
      isolation. MMP-2 protein and activity were determined by Western blot and
      zymography. The extracellular matrix (ECM) components type I and type IV collagen
      and laminin were analyzed by Western blot analysis and real-time PCR. RESULTS: HQ
      for 6 hours modestly decreased MMP-2. MMP-2 recovered only after co
      overexpression of MMP-14 and TIMP-2, but activity further decreased after HQ for
      18 hours. MMP-14 or TIMP-2 overexpression alone contributed as much as the co
      overexpression to the recovery of MMP-2 activity. MMP-2 protein seemed not to be
      altered. Type I collagen and laminin transcriptional levels remained unaffected,
      whereas type IV collagen transcripts decreased with HQ. Transfection with MMP-14
      and/or TIMP-2 contributed to the return of type IV collagen levels to normal. On
      the other hand, type I and IV collagens and laminin protein accumulated after HQ
      treatment, an effect prevented by transfection. CONCLUSIONS: MMP-14 and TIMP2
      contribute to the maintenance of adequate levels of MMP-2 activity in ARPE-19
      cells after oxidant injury. In addition, changes in ECM components may result as
      a consequence of MMP-2 activity and may be relevant to the progression of dry
      AMD.

PMID- 18055818
TI  - Insulin increases retinal hemorrhage in mild oxygen-induced retinopathy in the
      rat: inhibition by riluzole.
AB  - PURPOSE: Although hyperglycemia is likely the main stimulus for VEGF induction in
      diabetic retinopathy (DR), a switch from oral hypoglycemic therapy to parenteral
      insulin injection, despite producing better glucose control, sometimes
      paradoxically aggravates DR. The induction of VEGF by insulin, as observed in
      certain conditions, may be a plausible mechanism for this phenomenon. In the
      present study, to determine the role of insulin in proliferative diabetic
      retinopathy, the authors examined whether insulin treatment affected the outcome
      of oxygen-induced retinopathy (OIR) in rats and whether the anti-amyotrophic
      lateral sclerosis (ALS) drug riluzole with protein kinase C-inhibiting activity
      can attenuate the effects of insulin. METHODS: To examine in vivo the effects of
      insulin, mild OIR was produced in 7-day-old rat pups by raising them with a
      nursing mother in a 55% oxygen environment for 5 days. After that, rat pups were
      injected daily with subcutaneous saline or insulin (4 U/d) with or without
      additional riluzole injection (10 mg/kg/d, intraperitoneally) for 5 days in room
      air. RESULTS: Insulin treatment substantially increased VEGF levels, extraretinal
      vessel formation, matrix metalloproteinase activity, and the extent of retinal
      hemorrhage in rat pups with mild OIR compared with saline controls. Riluzole
      substantially reduced all these changes induced by insulin. CONCLUSIONS: In the
      present study, OIR was used as a surrogate model for DR because the core
      pathology and the VEGF-mediated mechanism are shared by both conditions. As in
      human DR, in rat pups with mild OIR, insulin treatment aggravated retinal
      hemorrhage, which was blocked by riluzole. Riluzole is a Food and Drug
      Administration-approved anti-ALS drug with a favorable adverse effect profile. It
      may be useful as an anti-VEGF treatment in DR, especially in reducing the retinal
      hemorrhage that often occurs shortly after the switch from oral hypoglycemics to
      parenteral insulin.

PMID- 18055819
TI  - Upregulation of VEGF in murine retina via monocyte recruitment after retinal
      scatter laser photocoagulation.
AB  - PURPOSE: This study was conducted to determine changes in the expression of
      vascular endothelial growth factor (VEGF) in murine retina after retinal scatter
      laser photocoagulation. METHODS: Photocoagulation (PHC) was performed on wild
      type C57BL/6J mice using a diode laser, and the eyes were enucleated 1, 2, 3, 4,
      7, and 14 days after laser treatment. VEGF and monocyte chemoattractant protein
      (MCP)-1 levels in the sensory retina and retinal pigmented epithelial (RPE) cells
      in both tissues were measured by ELISA. The VEGF mRNA was measured by real-time
      RT-PCR. Leukocyte infiltration into the RPE-choroid was determined by flow
      cytometry. VEGF comparisons between mice subjected to PHC and those treated with
      monocyte recruitment inhibitor (anti-MCP-1) were performed and statistically
      analyzed. The expression of VEGF and MCP-1 in the retina was determined by
      immunohistochemistry. RESULTS: VEGF protein levels significantly increased 1 day
      after PHC in both the RPE-choroid and the sensory retina. VEGF concentrations
      were maximum at day 3 after photocoagulation and stayed elevated until day 7. The
      number of choroid-infiltrating macrophages was markedly increased in mice with
      laser treatment compared with those without laser treatment. VEGF expression
      decreased after treatment with neutralized antibody to monocyte recruitment. We
      demonstrate that MCP-1 expression in the retina increased markedly after scatter
      laser photocoagulation by immunohistochemistry and ELISA. CONCLUSIONS: Retinal
      scatter laser photocoagulation induced upregulation of VEGF in the sensory retina
      and RPE-choroid at an early period. The authors speculate that the major source
      of VEGF in the retina after retinal scatter laser photocoagulation is the
      recruited monocytes.

PMID- 18055820
TI  - An assessment of the apex microarray technology in genotyping patients with Leber
      congenital amaurosis and early-onset severe retinal dystrophy.
AB  - PURPOSE: Leber congenital amaurosis (LCA) and early-onset severe retinal
      dystrophy (EOSRD) are genetically heterogeneous, with 11 genes currently
      implicated. The LCA chip may be used to interrogate many variants in one
      hybridization reaction. The purpose of this study was to assess the utility of
      this technology. METHODS: One hundred fifty-three patients with LCA and EOSRD
      were screened using an array (Asper Ophthalmics, Tartu, Estonia) containing 344
      published disease-causing variants and polymorphisms in eight genes: AIPL1,
      GUCY2D, CRB1, CRX, RPGRIP1, RPE65, MERTK, and LRAT. One hundred thirty-six
      probands underwent bidirectional sequencing of the full coding region of the
      RPE65 gene. The same technique was also used to confirm CRB1 and AIPL1 mutations
      initially identified with the Apex chip (Asper Ophthalmics). Single nucleotide
      polymorphism (SNP) analysis within control populations was performed for two
      variants, P701S and W21R, on the chip for GUCY2D. RESULTS: Of the possible
      109,392 interrogations, 3,346 (3.06%) failed on one strand whereas 259 (0.47%)
      failed on both. The chip reported mutations in 68 (44%) patients; 26 patients had
      two alleles identified (17%). Direct sequencing of RPE65 showed no discrepancies,
      whereas sequencing of AIPL1 and CRB1 revealed seven samples called erroneously.
      The SNP analysis of both GUCY2D variants revealed equal prevalence in the EOSRD
      panel and the normal population. Subsequent reanalysis, after excluding these
      polymorphisms, revealed one (18.3%) or two (11.7%) mutations identified in 46
      patients. When evaluated by diagnosis, 46% of patients with LCA had one or two
      mutations identified, compared with 24% of patients with EOSRD. CONCLUSIONS: This
      approach is a rapid and reasonably low-cost technique for identifying both
      previously identified mutations and common polymorphisms. The addition of further
      genes and mutations to the chip will improve its utility, though it is advised
      that all results be checked by direct sequencing.

PMID- 18055821
TI  - Identification of novel mutations in patients with Leber congenital amaurosis and
      juvenile RP by genome-wide homozygosity mapping with SNP microarrays.
AB  - PURPOSE: Leber congenital amaurosis (LCA) and juvenile retinitis pigmentosa (RP)
      cause severe visual impairment early in life. Thus far, mutations in 13 genes
      have been associated with autosomal recessive LCA and juvenile RP. The purpose of
      this study was to use homozygosity mapping to identify mutations in known LCA and
      juvenile RP genes. METHODS: The genomes of 93 consanguineous and
      nonconsanguineous patients with LCA and juvenile RP were analyzed for homozygous
      chromosomal regions by using SNP microarrays. This patient cohort was highly
      selected, as mutations in the known genes had been excluded with the LCA mutation
      chip, or a significant number of LCA genes had been excluded by comprehensive
      mutation analysis. Known LCA and juvenile RP genes residing in the identified
      homozygous regions were analyzed by sequencing. Detailed ophthalmic examinations
      were performed on the genotyped patients. RESULTS: Ten homozygous mutations,
      including seven novel mutations, were identified in the CRB1, LRAT, RPE65, and
      TULP1 genes in 12 patients. Ten patients were from consanguineous marriages, but
      in two patients no consanguinity was reported. In 10 of the 12 patients, the
      causative mutation was present in the largest or second largest homozygous
      segment of the patient's genome. CONCLUSIONS: Homozygosity mapping using SNP
      microarrays identified mutations in a significant proportion (30%) of
      consanguineous patients with LCA and juvenile RP and in a small number (3%) of
      nonconsanguineous patients. Significant homozygous regions which did not map to
      known LCA or juvenile RP genes and may be instrumental in identifying novel
      disease genes were detected in 33 patients.

PMID- 18055822
TI  - Photoreceptor protection against light damage by AAV-mediated overexpression of
      heme oxygenase-1.
AB  - PURPOSE: To investigate whether overexpression of the cytoprotective gene heme
      oxygenase-1 (HO-1) in photoreceptors by gene delivery attenuates cellular injury
      caused by intense light damage and to document the possible mechanisms of
      protection. METHODS: Recombinant adeno-associated virus type 5 (rAAV5) expressing
      the mouse HO-1 gene (mHO-1) was delivered to cyclic-light reared Sprague-Dawley
      (SD) rats by subretinal injection. Three weeks after transfer of HO-1 gene,
      animals were subjected to 2-hour intense light exposure then were returned to
      darkness. Expression of HO-1, p53, p38, and cellular FLICE inhibitory protein (c
      FLIP) at different times after intense light damage was evaluated by Western blot
      analysis. HO-1 transgene expression, along with expression of c-fos and bcl-2,
      was analyzed by immunohistochemistry. In addition, the protective effects of HO-1
      were evaluated by determining the morphology of the retina. Finally, apoptosis in
      photoreceptors was measured using TdT-dUTP terminal nick-end labeling (TUNEL) 24
      hours after photic injury. RESULTS: Exogenous administration of HO-1 by gene
      transfer led to HO-1 transgene expression in photoreceptors. Protection of retina
      by HO-1 overexpression is evident from the partially preserved retina structure
      and attenuated apoptosis in photoreceptors after photic injury. Concurrently,
      overexpression of HO-1 was associated with a decrease in the expression of c-fos
      and p53, an increase in the activation of p38 and bcl-2, and preserved the
      expression of c-FLIP. CONCLUSIONS: Overexpression of HO-1 in photoreceptors
      protected themselves from subsequent cellular damage caused by intense light
      exposure. The anti-apoptotic mechanisms of HO-1 may be related to the induction
      of p38, bcl-2, and c-FLIP and to the suppression of c-fos and p53.

PMID- 18055823
TI  - The effects of intravitreous bevacizumab on retinal neovascular membrane and
      normal capillaries in rabbits.
AB  - PURPOSE: To evaluate the effects of intravitreous bevacizumab in a rabbit retinal
      neovascularization model. METHODS: Twenty-four rabbits were divided into five
      groups. Group A included four rabbits; all other groups included five rabbits
      each. Group A received intravitreous VEGF only, and group E received
      intravitreous bevacizumab only. In groups B, C, and D, bevacizumab was injected
      at the same time, at day 2 and at week 1 after VEGF injection, respectively.
      Follow-up evaluations continued for 3 weeks and included color fundus
      photography, fluorescein angiography (FA), and optical coherence tomography
      (OCT). Enucleated eyes were processed for hematoxylin and eosin (H&E) staining.
      RESULTS: Intravitreous VEGF was associated with disc hyperemia, vascular
      dilatation and tortuosity, and fluorescein leakage at the disc and in the
      anterior chamber (AC) at day 2 and with formation of retinal neovascular
      membranes (NVM) by week 1. At weeks 2 and 3, the NVM was replaced by a fibrotic
      membrane and mild to moderate capillary nonperfusion. In groups B and C,
      injection of bevacizumab was very effective in preventing or stopping fluorescein
      leakage but was not able to prevent or reverse vascular dilatation and tortuosity
      completely. In group D, bevacizumab injection resulted in severe capillary
      nonperfusion at week 2. CONCLUSIONS: Intravitreous injection of VEGF in rabbits
      results in florid retinal neovascularization within the first week, followed by
      closure of normal capillaries by week 2. Early intravitreous injection of
      bevacizumab can prevent these effects, whereas late injection may be associated
      with more significant closure of normal capillaries. A sudden drop in effective
      VEGF concentration may be responsible for the closure of the normal capillaries.

PMID- 18055824
TI  - Antiangiogenic effects of bisphosphonates on laser-induced choroidal
      neovascularization in mice.
AB  - PURPOSE: To demonstrate that bisphosphonates inhibit laser-induced choroidal
      neovascularization (CNV) in vivo and downregulate angiogenic gene expression in
      retinal pigment epithelial cells in vitro. METHODS: Male C57BL/6 mice were
      treated with intraperitoneal injections of alendronate, clodronate, or saline at
      the onset (day 0) of experiments. CNV was induced by laser photocoagulation the
      next day, and fluorescein angiography (FA) was performed on experimental days 7
      and 14. Histologic and immunohistochemical examinations were performed on day 7.
      ARPE-19 cells were grown on multi-plate wells coated with type I collagen to
      induce the gene expression of VEGF and integrins. Alendronate or clodronate was
      applied for 3 days, and real-time PCR was performed to measure VEGF-A, VEGF-B,
      and VEGF-C and integrin-alphaV, integrin-beta1, and integrin-beta3. RESULTS:
      Alendronate and clodronate significantly suppressed the size of laser-induced
      CNV. Immunoreactivities for VEGF and integrin-alphaV were remarkably attenuated
      with alendronate and mildly reduced with clodronate. Alendronate significantly
      downregulated the gene expression profiles of VEGF and integrins, whereas
      clodronate had no effect in ARPE-19 cells. CONCLUSIONS: Although only adverse
      effects of bisphosphonate have been documented in the ophthalmologic literature,
      some therapeutic effects of bisphosphonates, including antiangiogenesis, may be
      expected in ocular diseases. Antiangiogenic mechanisms of bisphosphonates may
      vary; further investigation is needed.

PMID- 18055825
TI  - PDGF-C and -D induced proliferation/migration of human RPE is abolished by
      inflammatory cytokines.
AB  - PURPOSE: The role of growth factors and inflammation in regulating retinal
      pigment epithelial (RPE) function is complex and still poorly understood. The
      present study investigated human RPE cell proliferation and migration mediated by
      platelet-derived growth factor (PDGF) and inflammatory cytokines. METHODS: Human
      fetal RPE (hfRPE) cells were obtained as previously described. Gene expressions
      of PDGF isoforms and their receptors were detected using real-time PCR. Protein
      expression, activity, and localization of PDGFR-alpha and -beta were analyzed by
      Western blot and immunohistochemistry. BrdU incorporation and wound healing
      assays were used to test the effects of different PDGF isoforms and inflammatory
      cytokines on hfRPE proliferation and migration. Annexin-V and phalloidin staining
      were used to detect apoptosis and the actin cytoskeleton, respectively. RESULTS:
      PDGF-C and PDGF-D proteins are expressed in native human adult RPE, and mRNA
      levels are up to 100-fold higher than PDGF-A and -B. PDGFR-alpha and -beta
      proteins are expressed in native adult RPE and hfRPE (mainly localized to the
      apical membrane). In hfRPE, these receptors can be activated by PDGF-CC and -DD.
      PDGF-CC, -DD, and -BB significantly increased hfRPE proliferation, whereas PDGF
      DD, -BB, and -AB significantly increased cell migration. An inflammatory cytokine
      mixture (TNF-alpha/IL-1beta/IFN-gamma) completely inhibited the stimulatory
      effect of PDGF-BB, -CC, and -DD; in contrast, this mixture stimulated the
      proliferation of choroidal cells. This inflammatory cytokine mixture also induced
      apoptosis, significant disruption of actin filaments and zonula occludens (ZO-1),
      and a decrease in transepithelial resistance. CONCLUSIONS: These results suggest
      that proinflammatory cytokines in vivo can inhibit the proliferative effect of
      PDGF on human RPE and, at the same time, stimulate the proliferation of choroidal
      cells. They also suggest an important role of proinflammatory cytokines in
      overcoming local proliferative/wound-healing responses, thereby controlling the
      development of disease processes at the retina/RPE/choroid interface.

PMID- 18055826
TI  - Characterization of Wnt signaling during photoreceptor degeneration.
AB  - PURPOSE: The Wnt pathway is an essential signaling cascade that regulates
      multiple processes in developing and adult tissues, including differentiation,
      cellular survival, and stem cell proliferation. The authors recently demonstrated
      altered expression of Wnt pathway genes during photoreceptor death in rd1 mice,
      suggesting an involvement for Wnt signaling in the disease process. In this
      study, the authors investigated the role of Wnt signaling in retinal
      degeneration. METHODS: The Wnt signaling reporter mouse line Tcf-LacZ was crossed
      with retinal degeneration rd1 mice, and beta-galactosidase expression was used to
      localize Wnt signaling during photoreceptor death. To analyze the role of Wnt
      signaling activation, primary mixed retinal cultures were prepared, and XTT and
      TUNEL assays were used to quantify cell death. Luciferase reporter assays were
      used to measure Wnt signaling. RESULTS: The canonical Wnt signaling pathway was
      activated in Muller glia and the ganglion cell layer during rod photoreceptor
      degeneration in rd1/Tcf-LacZ mice. Wnt signaling was confirmed in cultured
      primary Muller glia. Furthermore, Wnt signaling activators protected
      photoreceptors in primary retinal cultures from H(2)O(2)-induced oxidative
      stress. The Wnt ligands Wnt5a, Wnt5b, Wnt10a, and Wnt13 were expressed in the
      degenerating retina and are candidate Wnt signaling activators in vivo.
      CONCLUSIONS: This study is the first demonstration that Wnt signaling is
      activated in the degenerating retina and that it protects retinal cultures from
      oxidative stress. These data suggest that Wnt signaling is a component of the
      glial protective response during photoreceptor injury. Therefore, inducing Wnt
      activation, alone or in combination with growth factors, may increase the
      threshold for apoptosis and halt or delay further photoreceptor degeneration.

PMID- 18055827
TI  - Triamcinolone acetonide-mediated oxidative injury in retinal cell culture:
      comparison with dexamethasone.
AB  - PURPOSE: To investigate the cytotoxicity of triamcinolone acetonide (TA) and
      dexamethasone (DXM) in various types of cells in retinal cell culture. METHODS:
      Primary rat retinal cell cultures were treated with 25 to 800 microg/mL TA (58
      microM-1.8 mM) or DXM (48 microM-1.6 mM) for 12 to 24 hours. Cell survival and
      death were assessed chemically by measuring cellular DNA contents using DNA
      binding fluorescent dye and morphologically by propidium iodide staining.
      Standard methods were used for immunocytochemistry, immunoblots, and ELISA
      measurements. Retinal cellular oxidative stress was measured under a fluorescence
      microscope using 5-(and-6)-carboxy-2',7'-difluorodihydrofluorescein diacetate.
      Changes in the level of several antioxidative proteins were investigated using
      immunoblots. RESULTS: Exposure to 100 to 800 microg/mL TA (0.23-1.8 mM) or 800
      microg/mL DXM (1.6 mM) for 24 hours caused a significant reduction in the number
      of retinal cells in culture, in a glucocorticoid receptor-independent manner. Of
      cell types in retinal cell cultures, astrocytes were most sensitive to TA and
      DXM. TA-induced cytotoxicity was mediated by oxidative stress. p38 kinase, c-Jun
      N-terminal kinase (JNK), caspase-1, and caspase-3 were involved in oxidative
      injury by TA. In addition, levels of antioxidative proteins increased after TA
      exposure. CONCLUSIONS: TA induces oxidative injury to cultured retinal cells in a
      glucocorticoid receptor-independent manner. These results suggest that TA has a
      significantly higher toxic potential in retinal cell culture than more water
      soluble DXM. For long-term anti-inflammatory effects, devices that are designed
      for the sustained release of water-soluble steroids may be safer.

PMID- 18055828
TI  - Glypican 4, a membrane binding protein for bactericidal/permeability-increasing
      protein signaling pathways in retinal pigment epithelial cells.
AB  - PURPOSE: Originally identified as a lipopolysaccharide binding protein with Gram
      negative bactericidal activity in the leukocytes, bactericidal/permeability
      increasing protein (BPI) has been shown to induce various effects in retinal
      cells in vivo and in vitro. METHODS: The authors recently reported that BPI can
      induce ERK1/2 and Akt activity and that it increases DNA synthesis in the bovine
      retinal pigment epithelial (RPE) and pericyte cells. The authors have extended
      the characterization of BPI interaction with membrane proteins from bovine RPE.
      Crude membrane pools from RPE were isolated, solubilized, and bound to rBPI(21)
      affinity column. Bound proteins were separated by SDS-PAGE and stained with
      Coomassie blue, which showed an intense band at 36 kDa consistently displaced by
      rBPI(21). RESULTS: Tandem mass spectrometry of the 36-kDa band suggested that
      cell surface protein glypican 4 (GPC4) serves as a putative BPI-binding protein.
      Heparitinase, phosphatidylinositol-specific phospholipase C, and anti-GPC4
      antibody suppressed BPI-induced ERK and Akt phosphorylation in bovine RPE.
      Moreover, heparitinase also inhibited BPI actions on VEGF and PDGF-B mRNA
      expression induced by H(2)O(2). CONCLUSIONS: These new findings suggest that GPC4
      is a specific binding protein for BPI on RPE to mediate the activation of ERK1/2,
      Akt, and the mRNA expressions of PDGF-B and VEGF.

PMID- 18055829
TI  - Intraocular CNTF reduces vision in normal rats in a dose-dependent manner.
AB  - PURPOSE: CNTF is a neuroprotective agent for retinal degenerations that can cause
      reduced electroretinogram (ERG) amplitudes. The goal of the present study was to
      determine the effects of intraocular delivery of CNTF on normal rat visual
      function. METHODS: Full-field scotopic and photopic ERG amplitudes and spatial
      frequency thresholds of the optokinetic response (OKR) of adult Long-Evans rats
      were measured before and after intravitreous injection of CNTF or subretinal
      delivery of adenoassociated virus-vectored CNTF (AAV-CNTF) into one eye. Visual
      acuity was also measured by using the Visual Water Task in AAV-CNTF-injected
      animals. Multiunit luminance thresholds were recorded in the superior colliculus
      after CNTF injection, and the eyes were examined histologically. RESULTS: In eyes
      injected with a high dose of CNTF, ERG amplitudes and OKR thresholds measured
      through CNTF-injected eyes were decreased by 45% to 70% within 6 days after
      injection. ERG amplitudes had begun to recover by 21 days, whereas OKR thresholds
      only began to recover after 56 days. Neither OKR thresholds nor ERG amplitudes
      fully recovered until 90 to 100 days. When measured in the superior colliculus at
      2 weeks after CNTF injection, luminance thresholds were elevated by 0.35 log
      units. In AAV-CNTF-injected eyes, OKR thresholds, and visual acuity were reduced
      by approximately 50% for at least 6 months, and scotopic and photopic ERG b-waves
      were reduced by 30% to 50%. Photoreceptor loss occurred in the injected regions
      in some of the eyes. By contrast, comparison of dose-response analysis with a
      dose-response study of light damage strongly suggests that therapeutic doses of
      CNTF exist that do not suppress ERG responses. CONCLUSIONS: Intraocular delivery
      of CNTF, which preserves photoreceptors in animal models of retinal degeneration,
      impairs visual function in normal rats at very high doses, but not at lower doses
      that still provide protection from constant light damage.

PMID- 18055830
TI  - Basal calcium entry in retinal pigment epithelial cells is mediated by TRPC
      channels.
AB  - PURPOSE: Ca(2+) is a major regulator of cell function. In the retinal pigment
      epithelium (RPE), intracellular free Ca(2+) concentration ([Ca(2+)](i)) is
      essential for the maintenance of normal retinal function. Therefore, accurate
      control of [Ca(2+)](i) is vital in these cells. Because Ca(2+) is permanently
      extruded from the cytosol, RPE cells need a basal Ca(2+) entry pathway that
      counteracts this Ca(2+) efflux. The purpose of this study was to identify the
      molecular basis of basal Ca(2+) entry into the RPE. METHODS: [Ca(2+)](i) was
      measured using Fura-2-loaded ARPE-19 cells. The expression pattern of TRPC
      channels was investigated by RT-PCR with RNA extracted from ARPE-19 cells and
      freshly isolated RPE cells from human donor eyes. RESULTS: In most cells, basal
      [Ca(2+)](i) is highly controlled by cell membranes that are only slightly
      permeable to Ca(2+) and by the activity of Ca(2+) pumps and transporters. The
      authors show here that RPE cells have a basal Ca(2+) conductance that is dose
      dependently blocked by La(3+). Basal [Ca(2+)](i) was also strongly reduced by the
      TRP channel blockers Gd(3+), Ni(2+), 2-APB, and SKF96365 and was insensitive to
      blockers of other Ca(2+) channels. In confirmation of this pharmacologic profile,
      RPE cells expressed TRPC1 and TRPC4 channels, as shown by RT-PCR experiments.
      CONCLUSIONS: Ca(2+) is needed for several permanently occurring regulatory
      processes in RPE cells. The Ca(2+) influx pathway identified in this study is
      essential to define a resting basal [Ca(2+)](i). This resting [Ca(2+)](i) may
      contribute, for example, to basal cytokine secretion essential for the
      maintenance of normal retinal function.

PMID- 18055831
TI  - Is optical coherence tomography really a new biomarker candidate in multiple
      sclerosis?--A structural and functional evaluation.
AB  - PURPOSE: To assess the structural and functional status of patients with multiple
      sclerosis (MS) without a history of optic neuritis. METHODS: Thirty-nine patients
      with MS who had reported no visual symptoms before and after the time of MS
      diagnosis were included. Thirty-eight healthy subjects were included as a control
      group. Retinal nerve fiber layer (RNFL) thickness was determined by optical
      coherence tomography. Pattern visual evoked potentials (PVEP), full-field
      electroretinogram (ERG), and multifocal electroretinogram (mfERG) were performed.
      RESULTS: There was a significant reduction (P = 0.011) only in temporal RNFL
      thickness in patients with MS. P(100) latency was significantly delayed with both
      60-min arc checks (P < 0.001) and 15-min arc checks (P < 0.001); however, P(100)
      amplitude was significantly reduced only in 60-min arc checks (P = 0.026). Rod
      response b-wave implicit time and standard combined response a- and b-wave
      implicit times were significantly delayed in patients with MS. Patients with MS
      with a delayed P(100) latency (21/39; 53.8%) had significantly reduced cone
      response b-wave amplitude and significantly delayed cone response a- and b-wave
      implicit times in ERG. mfERG results did not differ between MS and control
      subjects and between patients with a delayed and a normal P(100) latency. Pearson
      correlations between RNFL thickness and P(100) amplitude and latency in patients
      with MS were not significant (P > 0.05). CONCLUSIONS: There is no correlation
      between RNFL thickness and P(100) response in patients with MS. PVEP seems to be
      a more reliable biomarker in determining visual pathway involvement in patients
      with no history of optic neuritis.

PMID- 18055832
TI  - Bidirectional modulation of primary visual cortex excitability: a combined tDCS
      and rTMS study.
AB  - PURPOSE: In the motor cortex (M1), transcranial direct current stimulation (tDCS)
      can effectively prime excitability changes that are evoked by a subsequent train
      of repetitive transcranial magnetic stimulation (rTMS). The authors examined
      whether tDCS can also prime the cortical response to rTMS in the human visual
      cortex. METHODS: In nine healthy subjects, the authors applied tDCS (10 minutes;
      +/-1 mA) to the occipital cortex. After tDCS, they applied a 20-second train of 5
      Hz rTMS at 90% of phosphene threshold (PT) intensity. A similar rTMS protocol had
      previously demonstrated a strong priming effect of tDCS on rTMS-induced
      excitability changes in M1. PTs were determined with single-pulse TMS before and
      immediately after tDCS and twice after rTMS. RESULTS: Anodal tDCS led to a
      transient decrease in PT, and subsequent 5 Hz rTMS induced an earlier return of
      the PT back to baseline. Cathodal tDCS produced a short-lasting increase in PT,
      but 5 Hz rTMS did not influence the tDCS-induced increase in PT. In a control
      experiment on four subjects, a 20-second train of occipital 5 Hz rTMS left the PT
      unchanged, whereas a 60-second train produced a similar decrease in PT as anodal
      tDCS alone. CONCLUSIONS: Compared with previous work on the M1, tDCS and rTMS of
      the visual cortex only produce short-lasting changes in cortical excitability.
      Moreover, the priming effects of tDCS on subsequent rTMS conditioning are
      relatively modest. These discrepancies point to substantial differences in the
      modifiability of human motor and visual cortex.

PMID- 18055833
TI  - The oscillatory potentials of the dark-adapted electroretinogram in retinopathy
      of prematurity.
AB  - PURPOSE: To study the development of the electroretinographic (ERG) oscillatory
      potentials (OPs) in two rat models of ROP and in human subjects with a history of
      ROP. METHODS: Sprague-Dawley rats (n = 36) were studied longitudinally. Rat
      models of ROP were induced, either by exposure to alternating 50%/10% oxygen
      (50/10 model) from postnatal day (P) 0 to P14 or by exposure to 75% oxygen (75
      model) from P7 to P14. Control rats were reared in room air. Infant and adult
      human subjects with and without a history of ROP (n = 91) were also studied. Dark
      adapted ERGs were recorded and filtered to demonstrate the OPs. Discreet Fourier
      transform (DFT) allowed evaluation of the OP power spectrum. OP energy (E),
      dominant frequency (F(peak)), and sensitivity (log i(1/2)) were evaluated.
      RESULTS: In 50/10 model rats, E was low compared with that in the 75 model rats
      and control animals. F(peak) (approximately 95 Hz) did not vary with age or
      group. Intriguingly, log i(1/2) in 75 model rats was greater than that in
      controls or 50/10 model rats. Human adults with a history of ROP had lower-energy
      OPs than did the control adults, but infants with a history of ROP had higher
      energy OPs than did the control infants. F(peak) was lower (approximately 120 Hz)
      in infants than in adults (approximately 130 Hz). ROP did not affect log i(1/2)
      in humans. CONCLUSIONS: Differences between OPs in healthy rats and healthy
      humans were substantial, suggesting that OPs in rat models of ROP are unlikely to
      provide insight into the effects of ROP on human OPs. Indeed, neither ROP model
      studied showed a pattern of effects similar to that in human ROP.

PMID- 18055834
TI  - The relationship between visual field and retinal nerve fiber layer measurements
      in patients with multiple sclerosis.
AB  - PURPOSE: To investigate the relationship between visual function, measured by
      standard automated perimetry (SAP), and retinal nerve fiber layer (RNFL)
      thickness, measured by optical coherence tomography (OCT), in patients with
      multiple sclerosis (MS). METHODS: SAP and RNFL thickness were measured in
      patients with MS in 28 eyes with the last optic neuritis (ON) >or=6 months prior
      (ON group) and 33 eyes without ON history (non-ON group). Abnormal overall or
      quadrant RNFL thickness was defined by measured values below 5% of the norm. A
      whole visual field or a sector of the field was classified as abnormal by using
      cluster criteria on total-deviation plots. Agreement between SAP and OCT results
      in classifying eyes/sectors was presented as a percentage of observed agreement,
      along with the AC1 statistic, which corrects for chance agreement. Regression
      analyses were performed relating several SAP parameters and RNFL thickness in the
      ON group. RESULTS: ON eyes showed more loss of visual sensitivity (MD, P = 0.02)
      and more loss of RNFL thickness (P < 0.0001) than did non-ON eyes. SAP and OCT
      agreed in 86% (AC1 = 0.78) of eyes and 69% (AC1 = 0.38) of sectors in the ON
      group and 61% (AC1 = 0.33) of eyes and 66% (AC1 = 0.48) of sectors in the non-ON
      group. Overall RNFL thickness was related to MD (dB) by a simple exponential
      function (R(2) = 0.48), supporting a linear relationship between these measures
      when both are expressed on linear scales. Absolute Pearson correlation
      coefficients for overall RNFL thickness and several SAP parameters ranged from
      0.51 to 0.69. CONCLUSIONS: Good agreement between SAP and OCT was found in ON
      eyes but not in non-ON eyes or in individual sectors in either group. The
      findings in this study provide further support for the utility of combining
      structural and functional testing in clinical research on patients with MS, as
      well as in future neuroprotection trials for which the anterior visual pathways
      in patients with MS and optic neuritis may be used as a model.

PMID- 18055835
TI  - The effect of optical zone decentration on lower- and higher-order aberrations
      after photorefractive keratectomy in a cat model.
AB  - PURPOSE: To simulate the effects of decentration on lower- and higher-order
      aberrations (LOAs and HOAs) and optical quality, by using measured wavefront
      error (WFE) data from a cat photorefractive keratectomy (PRK) model. METHODS: WFE
      differences were obtained from five cats' eyes 19 +/-7 weeks after spherical
      myopic PRK for -6 D (three eyes) and -10 D (two eyes). Ablation-centered WFEs
      were computed for a 9.0 mm pupil. A computer model was used to simulate
      decentration of a 6-mm subaperture in 100-microm steps over a circular area of
      3000 microm diameter, relative to the measured WFE difference. Changes in LOA,
      HOA, and image quality (visual Strehl ratio based on the optical transfer
      function; VSOTF) were computed for simulated decentrations over 3.5 and 6.0 mm.
      RESULTS: Decentration resulted in undercorrection of sphere and induction of
      astigmatism; among the HOAs, decentration mainly induced coma. Decentration
      effects were distributed asymmetrically. Decentrations >1000 microm led to an
      undercorrection of sphere and cylinder of >0.5 D. Computational simulation of
      LOA/HOA interaction did not alter threshold values. For image quality (decrease
      of best-corrected VSOTF by >0.2 log units), the corresponding thresholds were
      lower. The amount of spherical aberration induced by the centered treatment
      significantly influenced the decentration tolerance of LOAs and log best
      corrected VSOTF. CONCLUSIONS: Modeling decentration with real WFE changes showed
      irregularities of decentration effects for rotationally symmetric treatments. The
      main aberrations induced by decentration were defocus, astigmatism, and coma.
      Treatments that induced more spherical aberration were less tolerant of
      decentration.

PMID- 18055836
TI  - Eccentric fixation in Stargardt's disease assessed by Tubingen perimetry.
AB  - PURPOSE: To measure eccentric fixation characteristics in visual fields of
      patients with Stargardt's disease. METHODS: The positions of fixation loci (FL)
      in the visual field were determined by Tubingen perimetry (TP), using the
      position of the blind spots in 173 patients. Altogether, 669 visual fields were
      measured at baseline and during follow-up. Twenty patients were also examined by
      scanning laser ophthalmoscope (SLO). RESULTS: Ninety-five of 173 patients showed
      a ring scotoma with central fixation in at least one test, which could persist
      for up to 18.8 years. The median age for a 50% chance of the development of
      eccentric fixation was 23.6 years. One hundred four patients (203 eyes) used
      eccentric fixation in at least one eye; in 154 eyes, the FL was placed below the
      scotoma and in 33 eyes to the left of it, in 11 to the right of it, and in 5
      above it. Once the FL was chosen, it remained within the same visual field area
      at subsequent tests, varying on average by 1.76 degrees. Compared with SLO
      results, the mean distance between FL and PRL was 1.90 degrees. CONCLUSIONS: It
      is possible to determine the position of the FL by perimetry with sufficient
      accuracy if the blind spot is well delimited. Stargardt patients can keep central
      fixation for different time intervals before changing to an eccentric FL. Most of
      them show an FL below the central scotoma, which is considered favorable for
      horizontal reading.

PMID- 18055840
TI  - Role of caveolin-1 in regulation of inflammation: different strokes for different
      folks.

PMID- 18055841
TI  - Role of CD38 in TNF-alpha-induced airway hyperresponsiveness.
AB  - CD38 is involved in normal airway function, IL-13-induced airway
      hyperresponsiveness (AHR), and is also regulated by tumor necrosis factor (TNF)
      alpha in airway smooth muscle (ASM) cells. This study aimed to determine whether
      TNF-alpha-induced CD38 upregulation in ASM cells contributes to AHR, a hallmark
      of asthma. We hypothesized that AHR would be attenuated in TNF-alpha-exposed CD38
      deficient (CD38KO) mice compared with wild-type (WT) controls. Mice (n = 6
      8/group) were intranasally challenged with vehicle control or TNF-alpha (50 ng)
      once and every other day during 1 or 4 wk. Lung inflammation and AHR, measured by
      changes in lung resistance after inhaled methacholine, were assessed 24 h
      following the last challenge. Tracheal rings were incubated with TNF-alpha (50
      ng/ml) to assess contractile changes in the ASM. While a single TNF-alpha
      challenge caused no airway inflammation, both multiple-challenge protocols
      induced equally significant inflammation in CD38KO and WT mice. A single
      intranasal TNF-alpha challenge induced AHR in the WT but not in the CD38KO mice,
      whereas both mice developed AHR after 1 wk of challenges. The AHR was suppressed
      by extending the challenges for 4 wk in both mice, although to a larger magnitude
      in the WT than in the CD38KO mice. TNF-alpha increased ASM contractile properties
      in tracheal rings from WT but not from CD38KO mice. In conclusion, CD38
      contributes to TNF-alpha-induced AHR after a brief airway exposure to the
      cytokine, likely by mediating changes in ASM contractile responses, and is
      associated with greater AHR remission following chronic airway exposure to TNF
      alpha. The mechanisms involved in this remission remain to be determined.

PMID- 18055842
TI  - Activation of Toll-like receptor 2 impairs hypoxic pulmonary vasoconstriction in
      mice.
AB  - Toll-like receptors (TLRs) mediate inflammation in sepsis, but their role in
      sepsis-induced respiratory failure is unknown. Hypoxic pulmonary vasoconstriction
      (HPV) is a unique vasoconstrictor response that diverts blood flow away from
      poorly ventilated lung regions. HPV is impaired in sepsis and after challenge
      with the TLR4 agonist lipopolysaccharide (LPS). Unlike TLR4 agonists, which are
      present only in Gram-negative bacteria, TLR2 agonists are ubiquitously expressed
      in all of the major classes of microorganisms that cause sepsis, including both
      Gram-positive and Gram-negative bacteria and fungi. We tested the hypothesis that
      (S)-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-N-palmitoyl-(R)-Cys-(S)-Ser(S)-Lys(4)
      OH, trihydrochloride (Pam3Cys), a TLR2 agonist, impairs HPV and compared selected
      pulmonary and systemic effects of Pam3Cys vs. LPS. HPV was assessed 22 h after
      challenge with saline, Pam3Cys, or LPS by measuring the increase in the pulmonary
      vascular resistance of the left lung before and during left lung alveolar hypoxia
      produced by left mainstem bronchus occlusion (LMBO). Additional endpoints
      included arterial blood gases during LMBO, hemodynamic parameters, weight loss,
      temperature, physical appearance, and several markers of lung inflammation.
      Compared with saline, challenge with Pam3Cys caused profound impairment of HPV,
      reduced systemic arterial oxygenation during LMBO, weight loss, leukopenia, and
      lung inflammation. In addition to these effects, LPS-challenged mice had lower
      rectal temperatures, metabolic acidosis, and were more ill appearing than Pam3Cys
      challenged mice. These data indicate that TLR2 activation impairs HPV and induces
      deleterious systemic effects in mice and suggest that TLR2 pathways may be
      important in sepsis-induced respiratory failure.

PMID- 18055843
TI  - Pathogenesis of the systemic inflammatory syndrome and acute lung injury: role of
      iron mobilization and decompartmentalization.
AB  - Changes in iron homeostatic responses routinely accompany infectious or
      proinflammatory insults. The systemic inflammatory response syndrome (SIRS) and
      the development of acute lung injury (ALI) feature pronounced systemic and lung
      specific alterations in iron/heme mobilization and decompartmentalization; such
      responses may be of pathological significance for both the onset and progression
      of acute inflammation. The potential for excessive iron-catalyzed oxidative
      stress, altered proinflammatory redox signaling, and provision of iron as a
      microbial growth factor represent obvious adverse aspects of altered in vivo iron
      handling. The release of hemoglobin during hemolytic disease or surgical
      procedures such as those utilizing cardiopulmonary bypass procedures further
      impacts on iron mobilization, turnover, and storage with associated implications.
      Genetic predisposition may ultimately determine the extent to which SIRS and
      related syndromes develop in response to such changes. The design of specific
      therapeutic interventions based on endogenous stratagems to limit adverse aspects
      of altered iron handling may prove of therapeutic benefit for the treatment of
      SIRS and ALI.

PMID- 18055844
TI  - Ontogeny of the eotaxins in human lung.
AB  - The ontogeny of the C-C chemokines eotaxin-1, eotaxin-2, and eotaxin-3 has not
      been fully elucidated in human lung. We explored a possible role for eotaxin in
      developing lung by determining the ontogeny of eotaxin-1 (CCL11), eotaxin-2
      (CCL24), eotaxin-3 (CCL26), and the eotaxin receptor, CCR3. We tested discarded
      surgical samples of developing human lung tissue using quantitative RT-PCR (QRT
      PCR) and immunostaining for expression of CCL11, CCL24, CCL26, and CCR3. We
      assessed possible functionality of the eotaxin-CCR3 system by treating lung
      explant cultures with exogenous CCL11 and analyzing the cultures for evidence of
      changes in proliferation and activation of ERK1/2, a signaling pathway associated
      with CCR3. QRT-PCR analyses of 22 developing lung tissue samples with gestational
      ages 10-23 wk demonstrated that eotaxin-1 mRNA is most abundant in developing
      lung, whereas mRNAs for eotaxin-2 and eotaxin-3 are minimally detectable. CCL11
      mRNA levels correlated with gestational age (P < 0.05), and immunoreactivity was
      localized predominantly to airway epithelial cells. QRT-PCR analysis detected
      CCR3 expression in 16 of 19 developing lung samples. Supporting functional
      capacity in the immature lung, CCL11 treatment of lung explant cultures resulted
      in significantly increased (P < 0.05) cell proliferation and activation of the
      ERK signaling pathway, which is downstream from CCR3, suggesting that
      proliferation was due to activation of CCR3 receptors by CCL11. We conclude that
      developing lung expresses the eotaxins and functional CCR3 receptor. CCL11 may
      promote airway epithelial proliferation in the developing lung.

PMID- 18055847
TI  - Current treatment and clinical trial developments for ductal carcinoma in situ of
      the breast.
AB  - Ductal carcinoma in situ (DCIS) is the fastest growing subtype of breast cancer,
      mainly because of the aging of our populations and improvements in diagnostic
      mammography and core biopsy. DCIS represents a proliferation of malignant
      appearing cells that have not invaded beyond the ductal basement membrane and is
      a precursor for the development of invasive breast cancer (IBC). Approximately
      40% of patients with DCIS treated with biopsy alone, without complete excision or
      further therapy, develop IBC. Most DCIS itself is harmless if it is detected and
      excised before it can progress to IBC, and the current approach to DCIS treatment
      is aimed at just that goal. Typically, it consists of multimodal treatment
      including segmental mastectomy followed by radiation therapy to the whole breast
      and then hormonal therapy or total mastectomy followed by hormonal therapy. This
      review discusses the state-of-the-art in DCIS detection and treatment and
      highlights promising new strategies in the care of DCIS patients. The data
      regarding the effectiveness of breast-conserving surgery versus total mastectomy,
      the possible avoidance of radiation therapy in some subgroups of patients, and
      the role of hormonal agents are reviewed. Neoadjuvant therapy and the use of
      trastuzumab for DCIS are currently under investigation and may be future
      treatment options for DCIS.

PMID- 18055845
TI  - Computational and experimental identification of novel human imprinted genes.
AB  - Imprinted genes are essential in embryonic development, and imprinting
      dysregulation contributes to human disease. We report two new human imprinted
      genes: KCNK9 is predominantly expressed in the brain, is a known oncogene, and
      may be involved in bipolar disorder and epilepsy, while DLGAP2 is a candidate
      bladder cancer tumor suppressor. Both genes lie on chromosome 8, not previously
      suspected to contain imprinted genes. We identified these genes, along with 154
      others, based on the predictions of multiple classification algorithms using DNA
      sequence characteristics as features. Our findings demonstrate that DNA sequence
      characteristics, including recombination hot spots, are sufficient to accurately
      predict the imprinting status of individual genes in the human genome.

PMID- 18055848
TI  - First-line chemotherapy for HER-2 negative metastatic breast cancer patients who
      received anthracyclines as adjuvant treatment.
AB  - The treatment decision for patients with metastatic breast cancer who have
      received anthracyclines within the course of adjuvant chemotherapy is
      troublesome, particularly if trastuzumab and hormonal treatment are not
      indicated. In the first part of this review we discuss the value of retreatment
      with anthracyclines, a topic that has been indirectly evaluated by retrospective
      studies with conflicting results and within a small phase III trial with a
      negative outcome. Evidence on liposomal anthracyclines is also reviewed. In the
      second part of the review, alternative options of first-line chemotherapy are
      discussed. These include taxanes as single agents, taxanes in combination with
      other cytotoxic drugs, combinations without anthracyclines and taxanes, and
      innovative treatments including target-based agents. Both the amount and the
      quality of evidence on these treatments are poor. Few phase III studies are
      available and most of them have been performed with registrative aims sponsored
      by the companies who own the winning drug. Beyond indications derived from such
      studies, there is a great need for more clinical research in this setting.

PMID- 18055849
TI  - Glucarpidase (carboxypeptidase g2) intervention in adult and elderly cancer
      patients with renal dysfunction and delayed methotrexate elimination after high
      dose methotrexate therapy.
AB  - OBJECTIVE: Leucovorin and extracorporeal removal of methotrexate (MTX) have
      limited efficacy in delayed MTX elimination after high-dose methotrexate (HD-MTX)
      therapy. Glucarpidase (carboxypeptidase G2) cleaves MTX into nontoxic
      metabolites, but experience with this enzyme is limited in adult patients. We
      evaluated the effects of glucarpidase intervention in adult and elderly patients
      with delayed MTX elimination. PATIENTS AND METHODS: Forty-three patients (age, 18
      78 years) with MTX serum concentrations (sMTX) of 1-1,187 micromol/l received
      glucarpidase, leucovorin rescue guided by MTX immunoassay, and standard
      supportive care. MTX and MTX metabolites were quantified in serum (24 patients)
      and urine (8 patients) by high-performance liquid chromatography. Contributory
      risk factors, toxicities, and survival were recorded in all patients. RESULTS:
      Glucarpidase was well tolerated and resulted in an immediate >97% reduction in
      sMTX, with a 0.2%-35% urinary recovery of the total MTX dose as inactive MTX
      metabolites. Forty (93%) of 43 patients had normalization (n = 25) or improvement
      (n = 15) of their serum creatinine. Frequent grade III-IV MTX toxicities were
      hematological (60%) and mucositis (35%); only eight (19%) patients developed
      grade III-IV nephrotoxicity. Ten (23%) of 43 patients experienced fatal
      complications associated with HD-MTX therapy. Patients with three or more
      contributory risk factors for delayed MTX elimination had a significantly poorer
      survival than patients with fewer than three risk factors (hazard ratio, 3.64;
      confidence interval, 1.14-17.54). CONCLUSIONS: Glucarpidase is well tolerated and
      produces a rapid inactivation of substantial amounts of MTX. However, overall
      results are still unsatisfactory in adult and elderly patients, suggesting that
      earlier recognition of delayed MTX elimination and more rapid intervention are
      needed.

PMID- 18055850
TI  - Locally advanced rectal cancer: what is the evidence for induction
      chemoradiation?
AB  - The concept of spatial cooperation in neoadjuvant chemoradiation (CRT) for
      locally advanced rectal cancer is attractive. Chemotherapy may, as a component of
      CRT, not only act as a radiosensitizing agent but also potentially eradicate
      distant micrometastases. Recent trials have demonstrated that the addition of
      concurrent 5-fluorouracil (5-FU)-based chemotherapy to radiation increases the
      pathological complete response rate, and reduces local recurrence, but as yet, a
      survival advantage has not been observed. AIMS: This review aims to examine the
      evidence for induction CRT in locally advanced rectal cancer. The endpoints of
      pathological complete response, a negative circumferential margin, sphincter
      sparing surgery, local control, disease-free survival (DFS), and overall survival
      (OS) are examined, as are acute and late morbidity, surgical complications, and
      late functional results. METHODS: The information to produce this review was
      compiled by searching PubMed and MEDLINE for English language articles published
      until April 2007. The search term included "induction, neoadjuvant, chemotherapy,
      radiotherapy, chemoradiation, combined modality" in association with rectal
      cancer. CONCLUSIONS: CRT in the European randomized trials of rectal cancer
      improves tumor downstaging, pathological complete response, and local control
      over radiotherapy alone, but does not translate into a benefit in terms of longer
      DFS or OS, or a higher chance of sphincter preservation. Metastatic disease
      remains a significant problem, which provides a strong rationale for the
      integration of a second cytotoxic drug, or biologically targeted agents.

PMID- 18055851
TI  - Commentary: rectal cancer an evolution of treatment.

PMID- 18055852
TI  - Liver transplantation for hepatocellular carcinoma in Asia.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer death, particularly
      in Asia where the major etiology, chronic hepatitis B virus infection, is
      endemic. The tumor frequently develops in a background of cirrhosis, and liver
      transplantation offers a chance to cure both the tumor and the underlying
      cirrhosis. The Milan criteria based on tumor size and number as an estimate of
      tumor burden are conventionally the gold standard in determining eligibility for
      transplantation, and the outcome is excellent. The shortage of organs from
      deceased donors has curtailed the adoption of extended criteria and led to the
      problems of long waiting times and dropouts. Several measures have been taken to
      tackle these issues, including prioritization of patients with HCC, use of
      pretransplant adjuvant treatment to prevent tumor progression, and living donor
      liver transplantation (LDLT). With a high incidence of HCC and a low organ
      donation rate, Asia has developed a distinctive pattern of indication and
      strategy in the application of liver transplantation. Over the last decade, the
      number of liver transplants in Asia has increased rapidly, by 10-fold, largely as
      a result of the development of LDLT. The proportion of patients who undergo liver
      transplantation for HCC is increasing and HCC comprises one third of the
      indication for liver transplantation in Asia. LDLT is the dominant strategy,
      accounting for 96% of the liver transplants for HCC. Many transplant programs
      accept patients beyond the Milan criteria, and the reported 3-year survival rate
      is about 60%. With the promotion of organ donation, better quantification of the
      benefit of LDLT for extended indications, and identification of predictors for
      survival, the practice of liver transplantation for HCC in Asia will continue to
      evolve.

PMID- 18055853
TI  - Gemcitabine-induced reversible posterior leukoencephalopathy syndrome: a case
      report and review of the literature.
AB  - Gemcitabine is a commonly used chemotherapeutic agent for a variety of tumor
      types. Although this nucleoside analogue antineoplastic agent is similar in
      structure to cytarabine, central nervous system toxicities have rarely been
      attributed to gemcitabine. Reversible posterior leukoencephalopathy syndrome
      (RPLS) is a rare but increasingly identifiable clinicoradiologic process in
      cancer patients associated with cytotoxic and immunosuppressive agents. The
      syndrome is characterized by acute to subacute onset of headache, nausea,
      vomiting, altered mental status, seizures, stupor, and visual disturbances. The
      pathophysiology of RPLS continues to remain controversial but likely involves
      loss of cerebrovascular autoregulation leading to arteriole leakage.
      Radiologically, posterior occipital white matter edema is noted, with
      characteristic findings on magnetic resonance imaging. Often the syndrome is
      reversible with treatment of concurrent hypertension or removal of the causative
      agent; however, failure to quickly recognize the syndrome and discontinue the
      offending agent may result in profound and permanent central nervous system
      dysfunction or death. This article describes a case of RPLS attributed to
      gemcitabine use for pancreatic cancer. Such a descriptive case serves as a
      platform for the discussion of the syndrome, proposed mechanisms of central
      nervous system damage, and review of the currently available literature on the
      topic. With increased awareness of RPLS by oncologists and other medical
      providers, cancer patient care may be improved and further insight into this
      complication of therapy through continued research may be gained.

PMID- 18055854
TI  - Ethical challenges in cancer research in children.
AB  - Clinical research has led to great advances in cancer therapy for children, and a
      greater proportion of children than adults with cancer participate in clinical
      trials. Despite this success, there remain important ethical challenges in
      conducting this research. There are challenges in obtaining informed consent and
      assent when children are research subjects; challenges arising from study design
      issues in phase III, II, or I clinical trials; and challenges related to the
      development of new classes of drugs, especially molecularly targeted therapies.
      It is important for researchers and clinicians to understand these challenges so
      that progress in cancer treatment is achieved in a sound ethical and regulatory
      fashion.

PMID- 18055855
TI  - Chordoma: the nonsarcoma primary bone tumor.
AB  - Chordomas are rare, slowly growing, locally aggressive neoplasms of bone that
      arise from embryonic remnants of the notochord. These tumors typically occur in
      the axial skeleton and have a proclivity for the spheno-occipital region of the
      skull base and sacral regions. In adults, 50% of chordomas involve the
      sacrococcygeal region, 35% occur at the base of the skull near the spheno
      occipital area, and 15% are found in the vertebral column. Craniocervical
      chordomas most often involve the dorsum sella, clivus, and nasopharynx. Chordomas
      are divided into conventional, chondroid, and dedifferentiated types.
      Conventional chordomas are the most common. They are characterized by the absence
      of cartilaginous or additional mesenchymal components. Chondroid chordomas
      contain both chordomatous and chondromatous features, and have a predilection for
      the spheno-occipital region of the skull base. This variant accounts for 5%-15%
      of all chordomas and up to 33% of cranial chordomas. Dedifferentiation or
      sarcomatous transformation occurs in 2%-8% of chordomas. This can develop at the
      onset of the disease or later. Aggressive initial therapy improves overall
      outcome. Patients who relapse locally have a poor prognosis but both radiation
      and surgery can be used as salvage therapy. Subtotal resection can result in a
      stable or improved status in as many as 50% of patients who relapse after primary
      therapy. Radiation therapy may also salvage some patients with local recurrence.
      One series reported a 2-year actuarial local control rate of 33% for patients
      treated with proton beam irradiation.

PMID- 18055856
TI  - The pharmacologic basis of ifosfamide use in adult patients with advanced soft
      tissue sarcomas.
AB  - The treatment outcome of patients with locally advanced and metastatic soft
      tissue sarcomas is poor. Doxorubicin is regarded as standard treatment, but its
      use is featured by the occurrence of cardiotoxicity. This hinders the
      administration of this drug at high doses or in combination with, in theory,
      attractive newly developed targeted drugs, such as vascular endothelial growth
      factor (VEGF) pathway inhibitors. The combination of doxorubicin and VEGF pathway
      inhibitors has been shown to yield an unacceptable high rate of cardiomyopathy.
      Ifosfamide is the only drug that consistently shows response rates comparable to
      those of doxorubicin. The lack of cardiotoxicity renders this drug a much more
      attractive alternative than doxorubicin to be explored at high doses or as part
      of new drug combinations. This review addresses the clinical pharmacology,
      metabolism, and present role of ifosfamide in the treatment of locally advanced
      and/or metastatic soft tissue sarcomas, excluding gastrointestinal stromal
      tumors, the Ewing-like sarcomas, and other small blue round cell tumors.
      Furthermore, this review focuses on the anticipated growing role of ifosfamide in
      the development of new treatment strategies.

PMID- 18055857
TI  - The NCCN Clinical Practice Guidelines on Venous Thromboembolic Disease:
      strategies for improving VTE prophylaxis in hospitalized cancer patients.
AB  - The risk for venous thromboembolism (VTE) is high in hospitalized cancer
      patients, and is associated with an elevated risk for recurrent thrombosis,
      bleeding complications, and use of health care resources. Thromboembolism is the
      second leading cause of death in hospitalized cancer patients. Thromboprophylaxis
      with unfractionated heparin or low-molecular-weight heparins has been clinically
      proven to reduce the risk for VTE and improve outcomes. However, VTE prophylaxis
      continues to be underprescribed in cancer patients. Recognizing the clinical
      burden of VTE in cancer patients, the National Comprehensive Cancer Network
      (NCCN) recently released guidelines for VTE prevention and management. These NCCN
      guidelines recommend evidence-based prophylactic anticoagulant therapy for all
      patients admitted to hospital with a diagnosis of cancer who do not have
      contraindications to anticoagulant use. However, there continue to be barriers to
      the implementation of clinical practice guidelines and appropriate use of VTE
      prophylaxis. Multifaceted active educational and electronic interventions are
      necessary to raise awareness and reduce the burden of cancer-associated
      thrombosis and its attendant consequences.

PMID- 18055858
TI  - The usefulness of nerve conduction studies in objectively assessing oxaliplatin
      induced peripheral neuropathy.

PMID- 18055860
TI  - Positron emission tomography-guided conformal fast neutron therapy for
      glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) continues to be a difficult therapeutic challenge.
      Our study was conducted to determine whether improved survival and tumor control
      could be achieved with modern delivery of fast neutron radiation using three
      dimensional treatment planning. Ten patients were enrolled. Eligibility criteria
      included pathologic diagnosis of GBM, age >or=18 years, and KPS >or=60. Patients
      underwent MRI and (18)F-fluorodeoxyglucose PET (FDG PET) as part of initial three
      dimensional treatment planning. Sequential targets were treated with noncoplanar
      fields to a total dose of 18 Gy in 16 fractions over 4 weeks. Median and 1-year
      overall survival were 55 weeks and 60%, respectively. One patient remains alive
      at last follow-up 255 weeks after diagnosis. Median progression-free survival was
      16 weeks, and all patients had tumor progression by 39 weeks. Treatment was
      clinically well tolerated, but evidence of mild to moderate gliosis and
      microvascular sclerosis consistent with radiation injury was observed at autopsy
      in specimens taken from regions of contralateral brain that received
      approximately 6-10 Gy. Fast neutron radiation using modern imaging, treatment
      planning, and beam delivery was feasible to a total dose of 18 Gy, but tumor
      control probability was poor in comparison to that predicted from a dose-response
      model based on older studies. Steep dose-response curves for both tumor control
      and neurotoxicity continue to present a challenge to establishing a therapeutic
      window for fast neutron radiation in GBM, even with modern techniques.

PMID- 18055861
TI  - Evaluation of glioma proliferation by 99mTc-Tetrofosmin.

PMID- 18055862
TI  - Prostatic hormonal carcinogenesis is mediated by in situ estrogen production and
      estrogen receptor alpha signaling.
AB  - It was recently demonstrated that antiestrogens prevented prostate cancer (PRCA)
      in men. The source of estradiol (E2) that contributes to carcinogenesis, as well
      as the selected estrogen receptor (ER) signaling pathway, is unknown. To evaluate
      estrogen's effects in carcinogenesis, we developed a new model of PRCA utilizing
      testosterone and E2 to stimulate PRCA. To determine whether local in situ
      production of E2 affected incidence of PRCA, aromatase-knockout (ArKO) mice were
      evaluated. In contrast to the wild-type mice, ArKO mice had reduced incidences of
      PRCA, which implicates in situ production of E2 as an important determinant of
      PRCA. To determine whether E2-mediated responses were due to ER alpha or ER beta
      signaling, ER alpha-knockout (alphaERKO) or ERbeta-knockout (betaERKO) mice were
      used. Prostates from betaERKO mice underwent biochemical and histological
      carcinogenesis similar to wild-type mice, whereas prostates from alphaERKO mice
      remained free of pathology. These data suggest that effective prevention of
      carcinogenesis will require antagonism of ER alpha but not ER beta. This mouse
      model provides a means to examine genetic gain and loss of function and determine
      the efficacy of therapeutics on prostatic carcinogenesis.

PMID- 18055863
TI  - Epigenetic regulation of dendritic cell-derived interleukin-12 facilitates
      immunosuppression after a severe innate immune response.
AB  - Patients who survive sepsis have significant deficiencies in their immune
      responses caused by poorly understood mechanisms. We have explored this
      phenomenon by studying dendritic cells (DCs) recovered from animals surviving
      severe peritonitis-induced sepsis, using the well-established cecal ligation and
      puncture (CLP) model. Immediately after the initiation of sepsis there is a
      depletion in DCs from the lung and spleen, which is followed by repopulation of
      these cells back to the respective organs. DCs recovered from surviving animals
      exhibited a significant and chronic suppression of interleukin-12 (IL-12), a key
      host defense cytokine. The suppression of DC-derived IL-12 persisted for at least
      6 weeks after CLP and was not due to immunoregulatory cytokines, such as IL-10.
      Using chromatin immunoprecipitation (ChIP) techniques, we have shown that the
      deficiency in DC-derived IL-12 was due to epigenetic alterations. Specifically,
      IL-12 expression was regulated by stable reciprocal changes in histone H3 lysine
      4 trimethylation (H3K4me3) and histone H3 lysine-27 dimethylation (H3K27me2), as
      well as changes in cognate histone methyltransferase (HMT) complexes on the
      Il12p35 and Il12p40 promoters. These data implicate histone modification enzymes
      in suppressing DC-derived IL-12, which may provide one of the mechanisms of long
      term immunosuppression subsequent to the septic response.

PMID- 18055864
TI  - Induction of hypomethylation and molecular response after decitabine therapy in
      patients with chronic myelomonocytic leukemia.
AB  - Decitabine's mechanism of action in chronic myelomonocytic leukemia remains
      incompletely understood. We studied the dynamics of neoplastic cell clearance
      during decitabine treatment (100 mg/m(2) per course every 4 weeks) using
      quantitative monitoring of mutant alleles by pyrosequencing. Patients with
      chronic myelomonocytic leukemia were first screened for JAK2 and NPM1 mutations,
      and 3 patients with mutations were identified. Mutant allele percentages in
      mononuclear cell DNA were followed after treatment, along with methylation of
      LINE1 and 10 other genes. The clearance of mutant alleles was modest after the
      first cycle, despite induction of hypomethylation. Delayed substantial clearance
      was observed after 2 to 4 cycles that correlated with clinical response. Two
      patients had complete disappearance of mutant alleles and sustained clinical
      remissions. In another patient, mutant allele was detectable at clinical
      remission, which lasted for 8 months. Our data suggest a predominantly
      noncytotoxic mechanism of action for decitabine, leading to altered biology of
      the neoplastic clone and/or normal cells. This trial was registered at
      www.ClinicalTrials.gov as #NCT00067808.

PMID- 18055865
TI  - Multicenter phase 3 study of the complement inhibitor eculizumab for the
      treatment of patients with paroxysmal nocturnal hemoglobinuria.
AB  - The terminal complement inhibitor eculizumab was recently shown to be effective
      and well tolerated in patients with paroxysmal nocturnal hemoglobinuria (PNH).
      Here, we extended these observations with results from an open-label, non-placebo
      controlled, 52-week, phase 3 clinical safety and efficacy study evaluating
      eculizumab in a broader PNH patient population. Eculizumab was administered by
      intravenous infusion at 600 mg every 7 +/- 2 days for 4 weeks; 900 mg 7 +/- 2
      days later; followed by 900 mg every 14 +/- 2 days for a total treatment period
      of 52 weeks. Ninety-seven patients at 33 international sites were enrolled.
      Patients treated with eculizumab responded with an 87% reduction in hemolysis, as
      measured by lactate dehydrogenase levels (P < .001). Baseline fatigue scores in
      the FACIT-Fatigue instrument improved by 12.2 +/- 1.1 points (P < .001).
      Eculizumab treatment led to an improvement in anemia. The increase in hemoglobin
      level occurred despite a reduction in transfusion requirements from a median of
      8.0 units of packed red cells per patient before treatment to 0.0 units per
      patient during the study (P < .001). Overall, transfusions were reduced 52% from
      a mean of 12.3 to 5.9 units of packed red cells per patient. Forty-nine patients
      (51%) achieved transfusion independence for the entire 52-week period.
      Improvements in hemolysis, fatigue, and transfusion requirements with eculizumab
      were independent of baseline levels of hemolysis and degree of thrombocytopenia.
      Quality of life measures were also broadly improved with eculizumab treatment.
      This study demonstrates that the beneficial effects of eculizumab treatment in
      patients with PNH are applicable to a broader population of PNH patients than
      previously studied. This trial is registered at http://clinicaltrials.gov as
      NCT00130000.

PMID- 18055866
TI  - Perivascular tissue factor is down-regulated following cutaneous wounding:
      implications for bleeding in hemophilia.
AB  - Healing of skin wounds is delayed in hemophilia B (HB) mice. HB mice do not bleed
      excessively at wounding, yet rebleed hours to days later. Tissue factor (TF)
      expression is up-regulated by inflammatory cytokines and has been linked to
      angiogenesis. We hypothesized that impaired thrombin generation in HB leads to
      impaired TF expression following injury. Punch biopsies were placed on wild-type
      (WT) and HB mice. Tissues from wound sites were immunostained for TF. Blood
      vessels are normally surrounded by a coat of pericytes expressing TF.
      Surprisingly, within a day after wounding TF disappeared from around nearby
      vessels; returning after 8 days in WT and 10 days in HB mice. The granulation
      tissue filling the wound during healing also lacked TF around angiogenic vessels.
      Thus, perivascular TF expression is down-regulated during wound healing. This may
      prevent thrombosis of neovessels during angiogenesis but renders hemophiliacs
      vulnerable to hemorrhage during healing.

PMID- 18055867
TI  - CD150- side population cells represent a functionally distinct population of long
      term hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) are a self-renewing population of bone marrow
      cells that replenish the cellular elements of blood throughout life. HSCs
      represent a paradigm for the study of stem-cell biology, because robust methods
      for prospective isolation of HSCs have facilitated rigorous characterization of
      these cells. Recently, a new isolation method was reported, using the SLAM family
      of cell-surface markers, including CD150 (SlamF1), to offer potential advantages
      over established protocols. We examined the overlap between SLAM family member
      expression with an established isolation scheme based on Hoechst dye efflux (side
      population; SP) in conjunction with canonical HSC cell-surface markers (Sca-1, c
      Kit, and lineage markers). Importantly, we find that stringent gating of SLAM
      markers is essential to achieving purity in HSC isolation and that the inclusion
      of canonical HSC markers in the SLAM scheme can greatly augment HSC purity.
      Furthermore, we observe that both CD150(+) and CD150(-) cells can be found within
      the SP population and that both populations can contribute to long-term
      multilineage reconstitution. Thus, using SLAM family markers to isolate HSCs
      excludes a substantial fraction of the marrow HSC compartment. Interestingly,
      these 2 subpopulations are functionally distinct, with respect to lineage output
      as well as proliferative status.

PMID- 18055868
TI  - Monitoring the response and course of chronic myeloid leukemia in the modern era
      of BCR-ABL tyrosine kinase inhibitors: practical advice on the use and
      interpretation of monitoring methods.

PMID- 18055870
TI  - The BXH2 mutation in IRF8 differentially impairs dendritic cell subset
      development in the mouse.
AB  - Among dendritic cell (DC) subsets, CD8alpha(+) DCs and plasmacytoid DCs (pDCs)
      produce high levels of IL12 and type I interferons (IFNs), respectively, and
      confer early innate immunity. Development of CD8alpha(+) DCs and pDCs requires
      the interferon regulatory factor 8 (IRF8). Recently, a spontaneous point mutation
      was identified in the Irf8/Icsbp gene in the BXH2 mouse, which exhibits an
      immunodeficient phenotype similar to the IRF8 knockout (KO) mouse. We show that
      this mutation, designated IRF8(R294C), abolishes the development of CD8alpha(+)
      DCs without impairing pDC development, and eliminates production of IL12p40,
      while retaining that of type I IFNs. Electrophoretic mobility shift and chromatin
      immunoprecipitation assays indicated that IRF8(R294C) failed to interact with
      partner transcription factors and did not bind certain promoters that require
      partner interactions. Together, this work indicates that IRF8-partner
      interactions play different roles in CD8alpha(+) DCs and pDCs, revealing a
      mechanistic separation that underlies development of these DC subsets.

PMID- 18055869
TI  - The prognostic significance of a positive direct antiglobulin test in chronic
      lymphocytic leukemia: a beneficial effect of the combination of fludarabine and
      cyclophosphamide on the incidence of hemolytic anemia.
AB  - Autoimmune hemolytic anemia (AHA) is a common complication in chronic lymphocytic
      leukemia (CLL). The UK LRF CLL4 trial is the largest prospective trial in CLL to
      examine the prognostic impact of both a positive direct antiglobulin test (DAT)
      and AHA. Seven-hundred seventy-seven patients were randomized to receive
      chlorambucil or fludarabine, alone or with cyclophosphamide (FC). The incidence
      pretreatment of a positive DAT was 14%. Ten percent developed AHA. The DAT
      correctly predicted the development, or not, of AHA after therapy in 83% of
      cases, however only 28% of DAT-positive patients developed AHA. Of 299 patients
      tested both before and after treatment, those treated with single-agent
      fludarabine were most likely to remain DAT positive and to change from negative
      to positive. Patients treated with chlorambucil or fludarabine were more than
      twice as likely to develop AHA as those receiving FC. In a multivariate analysis,
      stage C disease and high beta2 microglobulin were independent predictors of a
      positive DAT result. AHA, or a positive DAT, with or without AHA, independently
      predicted for reduced overall survival (OS). Four deaths, all on fludarabine
      monotherapy, were attributed to AHA. In conclusion, DAT status at the time of
      initiation of therapy provides a new prognostic indicator, although FC may
      protect against AHA. This trial was registered at http://isrctn.org as no.
      58585610.

PMID- 18055871
TI  - Aberrant activation of stress-response pathways leads to TNF-alpha oversecretion
      in Fanconi anemia.
AB  - Fanconi anemia (FA), an inherited syndrome that associates bone marrow failure,
      cancer predisposition, and genetic instability, is characterized by an
      overproduction of the myelosuppressive cytokine TNF-alpha through unknown
      mechanisms. We demonstrate here that FANC pathway loss-of-function results in the
      aberrant activation of 2 major stress-signaling pathways: NF-kappaB and MAPKs.
      These responses are independent on TNF-alpha expression. On the contrary,
      inhibition of the MAPK pathways normalizes TNF-alpha oversecretion in FA.
      Moreover, our data show that the overexpression of the matrix metalloproteinase
      MMP-7 is the key event directly responsible for the high rate of TNF-alpha
      shedding and release from the cytoplasmic membrane in FA. TNF-alpha
      overproduction is, indeed, normalized by MMP-7 inhibition. Finally, MAPK
      inhibition impacts on MMP-7 overexpression. Evidence is provided of the existence
      of a linear pathway in which FANC mutations activate MAPK signaling that induces
      MMP-7 overexpression leading, in fine, to TNF-alpha oversecretion. TNF-alpha may,
      in turn, sustain or amplify both MAPKs and NF-kappaB activation. Aberrant
      expression or activity of NF-kappaB and/or MAPKs has been already involved in
      bone marrow failure and leukemia, and their inhibition offered clinical benefit
      for patients. In conclusion, our data provide a strong rationale for new clinical
      trials on FA patients.

PMID- 18055872
TI  - Cerebral border zones between distal end branches of intracranial arteries: MR
      imaging.
AB  - This study had institutional review board approval; informed consent was obtained
      from all participants. The study purpose was to prospectively determine whether a
      longer arterial transit time (ATT), from the proximal vasculature in the neck
      toward the distal end branches of the intracranial arteries, can be utilized to
      identify cerebral border zone regions. A magnetic resonance (MR) imaging method
      based on noninvasive arterial spin-labeling (ASL) perfusion MR imaging with image
      acquisition at a series of increasing delay times was used to quantify regional
      ATTs. Fifteen healthy volunteers (age range, 22-34 years; nine men, six women)
      were included. ASL perfusion MR imaging demonstrated an increase in ATT in the
      cerebral border zone regions, extending from the frontal and occipital horns of
      the lateral ventricle to the frontal and parietooccipital cortices, relative to
      ATT in non-border zone regions. Cerebral blood flow and arterial blood volume in
      these anterior and posterior border zone regions were significantly lower (P <
      .001) than in non-border zone regions.

PMID- 18055873
TI  - Automated quantification of myocardial infarction from MR images by accounting
      for partial volume effects: animal, phantom, and human study.
AB  - Ethics committees approved human and animal study components; informed written
      consent was provided (prospective human study [20 men; mean age, 62 years]) or
      waived (retrospective human study [16 men, four women; mean age, 59 years]). The
      purpose of this study was to prospectively evaluate a clinically applicable
      method, accounting for the partial volume effect, to automatically quantify
      myocardial infarction from delayed contrast material-enhanced magnetic resonance
      images. Pixels were weighted according to signal intensity to calculate infarct
      fraction for each pixel. Mean bias +/- variability (or standard deviation),
      expressed as percentage left ventricular myocardium (%LVM), were -0.3 +/- 1.3
      (animals), -1.2 +/- 1.7 (phantoms), and 0.3 +/- 2.7 (patients), respectively.
      Algorithm had lower variability than dichotomous approach (2.7 vs 7.7 %LVM, P <
      .01) and did not differ from interobserver variability for bias (P = .31) or
      variability (P = .38). The weighted approach provides automatic quantification of
      myocardial infarction with higher accuracy and lower variability than a
      dichotomous algorithm.

PMID- 18055874
TI  - Reliability and validity of MR image lung volume measurement in fetuses with
      congenital diaphragmatic hernia and in vitro lung models.
AB  - PURPOSE: To prospectively assess the reliability of magnetic resonance (MR) image
      volume measurement in fetuses with congenital diaphragmatic hernia (CDH) and the
      reliability and validity of measurements in in vitro lung models. MATERIALS AND
      METHODS: This study was approved by the ethics committee, and informed consent
      was obtained. MR fetal lung volume (FLV) was measured in 40 consecutive fetuses
      with CDH by using half-Fourier acquired single-shot turbo spin-echo MR imaging
      and true fast imaging with steady-state precession at 24-36 weeks gestation (mean
      gestational age, 30.6 weeks +/- 3.5 [standard deviation]). Lung volumes were
      independently assessed in three orthogonal section planes by two experienced
      observers. Additionally, 28 in vitro lung models of defined volumes of 1-60 mL
      were evaluated the same way. To assess measurement validity and reliability, the
      intraclass correlation coefficient (ICC) and the Bland-Altman plot were used.
      RESULTS: The interobserver reliability was high for both the lung models and FLV
      measurements (ICC, 0.999 and 0.928, respectively). Measurement validity was also
      good, with a mean difference between the calculated volume and the true volume of
      0.4 mL (95% confidence interval: 0.30, 0.48). Measurement reliability and
      validity did not depend, to any considerable degree, on imaging plane or sequence
      (ICC range, 0.878-0.999) or on total volume. CONCLUSION: The reliability and
      validity of MR volume measurements are high. The method is independent of the
      sequence and the imaging plane and can be performed with a very good
      interobserver agreement, even in small volumes.

PMID- 18055875
TI  - Functional antagonism between endogenous neuropeptide Y and calcitonin gene
      related peptide in mesenteric resistance arteries.
AB  - To test the hypothesis that endogenous neuropeptide Y (NPY) counteracts the
      vasodilator effects of calcitonin gene-related peptide (CGRP), we used isolated
      mesenteric resistance arteries of rats and mice. With immunohistochemistry, we
      observed CGRP-containing fibers along and in the vicinity of a subset of NPY- or
      tyrosine hydroxylase-immunoreactive fibers. The CGRP1 receptor component
      calcitonin-related-like receptor was expressed by periarterial nerves and smooth
      muscle cells, whereas receptor activity-modifying protein 1 was observed
      primarily on the smooth muscle. In organ chambers, exogenous CGRP caused
      relaxations that were reversed by exogenous NPY. The effects were inhibited by 1
      piperidinecarboxamide, N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]
      carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)-methyl]-2-oxoethyl]-4
      (1,4-dihydro-2-oxo-3(2H)-quinazolinyl) (BIBN4096BS, a CGRP1 receptor antagonist;
      pK(B) = 8.54 +/- 0.52) and (R)-NZ-(diphenylacetyl)-N-[(4
      hydroxyphenyl)methyl]argininamide (BIBP3226, a Y1 antagonist; pK(B) = 7.00 +/-
      0.49), respectively. Pretreatment with capsaicin (1 muM; 20 min) and the presence
      of BIBN4096BS (20 nM) increased contractile responses to K(+) (20-40 mM) and
      electrical field stimulation (EFS; 1-32 Hz). NPY increased contractile responses
      to K(+) and BIBP3226 (400 nM) reduced contractile responses to EFS. These effects
      were inhibited by capsaicin and BIBN4096BS, respectively. Furthermore, the
      relaxing effect of exogenous CGRP (10 nM) during phenylephrine-induced
      contraction (30 muM) was reversed by EFS, and this effect was reduced in the
      presence of BIBP3226. We confirmed that bioactive concentrations of endogenous
      CGRP and NPY can be released from periarterial sensory-motor and sympathetic
      nerves, respectively, and we demonstrate for the first time functional antagonism
      between endogenous NPY and CGRP at the level of the smooth muscle.

PMID- 18055876
TI  - Inhibiting protease-activated receptor 4 limits myocardial ischemia/reperfusion
      injury in rat hearts by unmasking adenosine signaling.
AB  - Harnessing endogenous cardioprotectants is a novel therapeutic strategy to combat
      ischemia/reperfusion (I/R) injury. Thrombin causes I/R injury, whereas exogenous
      adenosine prevents I/R injury. We hypothesized that blocking thrombin receptor
      activation with a protease-activated receptor (PAR) 4 antagonist would unmask the
      cardioprotective effects of endogenous adenosine. The protective role of two
      structurally unrelated PAR4 antagonists, trans-cinnamoyl-YPGKF-amide (tc-Y-NH(2))
      and palmitoyl-SGRRYGHALR-amide (P4pal10), were evaluated in two rat models of
      myocardial I/R injury. P4pal10 (10 microg/kg) treatment before ischemia
      significantly decreased infarct size (IS) by 31, 21, and 19% when given before,
      during, and after ischemia in the in vivo model. tc-Y-NH(2) (5 microM) treatment
      before ischemia decreased IS by 51% in the in vitro model and increased recovery
      of ventricular function by 26%. To assess whether the cardioprotective effects of
      PAR4 blockade were due to endogenous adenosine, isolated hearts were treated with
      a nonselective adenosine receptor blocker, 8-sulfaphenyltheophylline (8-SPT), and
      tc-Y-NH(2) before ischemia. 8-SPT abolished the protective effects of tc-Y-NH(2)
      but did not affect IS when given alone. Adenosine-mediated survival pathways were
      then explored. The cardioprotective effects of tc-Y-NH(2) were abolished by
      inhibition of Akt (wortmannin), extracellular signal-regulated kinase 1/2
      [PD98059 (2'-amino-3'-methoxyflavone)], nitric-oxide synthase [N(G)-monomethyl-l
      arginine (l-NMA)], and K(ATP) channels (glibenclamide). PD98059, l-NMA, and
      glibenclamide alone had no effect on cardioprotection in vitro. Furthermore,
      inhibition of mitochondrial K(ATP) channels [5-hydroxydecanoic acid (5-HD)] and
      sarcolemmal K(ATP) channels (sodium (5-(2-(5-chloro-2-methoxybenzamido)ethyl)-2
      methoxyphenylsulfonyl)(methylcarbamothioyl)amide; HMR 1098) abolished P4pal10
      induced cardioprotection in vivo. Thrombin receptor blockade by PAR4 inhibition
      provides protection against injury from myocardial I/R by unmasking adenosine
      receptor signaling and supports the hypothesis of a coupling between thrombin
      receptors and adenosine receptors.

PMID- 18055877
TI  - Thionamides inhibit the transcription factor nuclear factor-kappaB by suppression
      of Rac1 and inhibitor of kappaB kinase alpha.
AB  - Thionamides, inhibitors of the thyroid peroxidase-mediated iodination, are
      clinically used in the treatment of hyperthyroidism. However, the use of
      antithyroid drugs is associated with immunomodulatory effects, and recent studies
      with thionamide-related heterocyclic thioderivates demonstrated direct anti
      inflammatory and immunosuppressive properties. Using primary human T-lymphocytes,
      we show that the heterocyclic thionamides carbimazole and propylthiouracil
      inhibit synthesis of the proinflammatory cytokines tumor necrosis factor
      (TNF)alpha and interferon (IFN)gamma. In addition, DNA binding of nuclear factor
      (NF)-kappaB, a proinflammatory transcription factor that regulates both TNFalpha
      and IFNgamma synthesis, and NF-kappaB-dependent reporter gene expression were
      reduced. Abrogation of NF-kappaB activity was accompanied by reduced
      phosphorylation and proteolytic degradation of inhibitor of kappaB
      (IkappaB)alpha, the inhibitory subunit of the NF-kappaB complex. Carbimazole
      inhibited NF-kappaB via the small GTPase Rac-1, whereas propylthiouracil
      inhibited the phosphorylation of IkappaBalpha by its kinase inhibitor of kappaB
      kinase alpha. Methimazole had no effect on NF-kappaB induction, demonstrating
      that drug potency correlated with the chemical reactivity of the thionamide
      associated sulfur group. Taken together, our data demonstrate that thioureylenes
      with a common, heterocyclic structure inhibit inflammation and immune function
      via the NF-kappaB pathway. Our results may explain the observed remission of
      proinflammatory diseases upon antithyroid therapy in hyperthyroid patients. The
      use of related thioureylenes may provide a new therapeutic basis for the
      development and application of anti-inflammatory compounds.

PMID- 18055878
TI  - Omeprazole stimulates the induction of human insulin-like growth factor binding
      protein-1 through aryl hydrocarbon receptor activation.
AB  - 5-Methoxy-2-{(4-methoxy-3,5-dimethyl-pyridin-2-yl)methylsulfinyl}-3H
      benzoimidazole (omeprazole), a benzoimidazole-derived gastric H(+)/K(+)-ATPase
      proton pump inhibitor (PPI) extensively prescribed for the treatment of
      gastroesophageal acid reflux disease, can stimulate the expression of CYP1A1 via
      activation of the human aryl hydrocarbon receptor (hAhR) in an apparent nonligand
      binding manner. Here, we have examined the effect of nonclassical, i.e.,
      nonligand binding, AhR activation by omeprazole upon human insulin-like growth
      factor binding protein (hIGFBP)-1, a secreted phosphoprotein involved in
      regulation of insulin-like growth factor-I/II bioavailability and mitogenic
      activity. Analysis of the proximal promoter of the hIGFBP-1 gene reveals the
      presence of an aryl hydrocarbon binding/dioxin response element (DRE).
      Quantitative mRNA analysis revealed hIGFBP-1 expression to be responsive to both
      ligand (TCDD) and nonligand (omeprazole) modes of hAhR activation in the human
      hepatocarcinoma HepG2 cell line. Furthermore, mutagenesis of the DRE renders the
      hIGFBP-1 promoter unresponsive to both compounds in HepG2 cells. Likewise, small
      interfering RNA-mediated hAhR ablation inhibits TCDD and omeprazole-dependent
      hIGFBP-1 induction, as determined by quantitative mRNA analysis. Cotreatment with
      cycloheximide further suggests a direct transcriptional role for hAhR at the
      hIGFBP-1 promoter. Omeprazole exposure prompted a significant increase in both
      hIGFBP-1 mRNA and secreted protein from HepG2 cells. In addition, we present in
      vitro evidence indicating that omeprazole at a concentration comparable with that
      found circulating in subjects undergoing PPI therapy can stimulate the expression
      of hIGFBP-1. These data demonstrate that activation of hAhR by pharmaceuticals
      such as omeprazole can alter IGFBP-1 expression and thus may influence IGFBP-1
      dependent physiological processes.

PMID- 18055879
TI  - 7-Chloro-5-(4-hydroxyphenyl)-1-methyl-3-(naphthalen-2-ylmethyl)-4,5-dihydro-1H
      benzo[b][1,4]diazepin-2(3H)-one (Bz-423), a benzodiazepine, suppresses
      keratinocyte proliferation and has antipsoriatic activity in the human skin
      severe, combined immunodeficient mouse transplant model.
AB  - 7-Chloro-5-(4-hydroxyphenyl)-1-methyl-3-(naphthalen-2-ylmethyl)-4,5-dihydro-1H
      benzo[b][1,4]diazepin-2(3H)-one (Bz-423) is a benzodiazepine that has cytotoxic
      and cytostatic activity against a variety of cells in vivo and in vitro. In the
      present study, we demonstrate that Bz-423 (formulated for topical delivery)
      reduces epidermal hyperplasia in human psoriatic skin after transplantation to
      severe, combined immunodeficient (scid) mice. Bz-423 also suppresses the
      hyperplasia that develops in nonpsoriatic human skin as a consequence of
      transplantation to scid mice. Proliferation of human epidermal keratinocytes in
      monolayer culture was suppressed by Bz-423 at concentrations of 0.5 to 2.0 muM
      (noncytotoxic concentrations). Keratinocyte growth inhibition was accompanied by
      increased oxidant generation in Bz-423-treated cells, and treatment with vitamin
      E along with Bz-423 reversed the growth inhibition. Growth inhibition was
      accompanied by a redistribution of beta-catenin from a cytoplasmic pool to the
      cell membrane and by reduced levels of c-myc and cyclin D1 (two molecules
      associated with Wnt pathway signaling). Several analogs of Bz-423 were examined
      for antiproliferative activity against human epidermal keratinocytes and human
      dermal fibroblasts in monolayer culture. Each of the analogs tested suppressed
      growth of both cell types, but in all cases, keratinocytes were more sensitive
      than fibroblasts. Two of the compounds were found to suppress epidermal
      hyperplasia induced with all-trans retinoic acid in organ cultures of human skin.
      Taken together, these data show that Bz-423 and certain analogs produce
      biological responses in skin cells in vitro and in vivo that are consistent with
      therapeutic goals for treating psoriasis or epidermal hyperplasia resulting from
      other causes.

PMID- 18055881
TI  - A proposal: publication guidelines for healthcare improvement education reports.

PMID- 18055880
TI  - Succinate ameliorates energy deficits and prevents dysfunction of complex I in
      injured renal proximal tubular cells.
AB  - We previously reported that mitochondrial function, intracellular ATP levels, and
      complex I activity are decreased in renal proximal tubular cells (RPTC) after
      oxidant (tert-butyl hydroperoxide; TBHP)-induced injury. This study examined the
      hypothesis that succinate supplementation decreases mitochondrial dysfunction,
      ameliorates energy deficits, and increases viability in TBHP-injured RPTC. Basal
      and uncoupled respirations in injured RPTC decreased 33 and 35%, respectively,
      but remained unchanged in injured RPTC supplemented with 10 mM succinate
      (electron donor to respiratory complex II). State 3 respiration supported by
      electron donors to complex I decreased 40% in injured RPTC but improved
      significantly by succinate supplements. The activity of mitochondrial complex I
      in TBHP-injured RPTC decreased 48%, whereas complex II activity remained
      unchanged. Succinate supplementation prevented decreases in complex I activity.
      ATP levels decreased 43% in injured RPTC but were maintained in injured cells
      supplemented with succinate. Lipid peroxidation increased 19-fold in injured RPTC
      but only 9-fold in injured cells supplemented with succinate. Exposure of primary
      cultures of RPTC to TBHP produced 24% cell injury and lysis but no apoptosis. In
      contrast, no cell lysis was found in RPTC supplemented with succinate. We
      conclude that mitochondrial dysfunction and energy deficits in oxidant-injured
      RPTC are ameliorated by succinate, and we propose that succinate supplementation
      may prove therapeutically valuable. Succinate 1) uses an alternate pathway of
      mitochondrial energy metabolism, 2) improves activity of complex I and oxidation
      of substrates through complex I, and 3) decreases oxidative stress and cell lysis
      in oxidant-injured RPTC.

PMID- 18055882
TI  - Extracting information from hospital records: what patients think about consent.
AB  - BACKGROUND AND OBJECTIVE: There is increasing regulation and concern about the
      use of material from patients' records. Studies on patients' views have focused
      on primary care and on use of material for research. This study investigated
      patients' preferences about whether and how doctors should seek permission for
      use of specified items of anonymised information from their hospital records for
      clinical audit, teaching, national data collection and research. METHOD: A
      specially designed questionnaire sent to recently discharged patients under the
      care of medical and surgical specialists. RESULTS: 166/316 (53%) patients
      completed the questionnaires. The percentage of respondents who "definitely
      wanted" or "preferred" to be asked for permission for use of anonymised
      information was highest for medical history (21%) and reasons for treatment
      (20%). The purpose for which information was requested (eg, research, audit) made
      little difference to the overall percentages (range 10-12%). 21 (13%) patients
      "definitely wanted" to be asked for permission for use of some item or proposed
      use of information--most had no preference or preferred not to be asked. The most
      popular method for asking permission was signing a form while in hospital, rather
      than by specific requests later. CONCLUSIONS: Most hospital patients have no
      preference or prefer not to be asked permission for doctors to use information
      from their records. About 1 in 8 patients would like to be asked for permission,
      some even for clinical audit of outcomes--although a minority, this could
      compromise thorough clinical audit. Systems for obtaining permission when
      patients are admitted to hospital need to be considered. Resolution of
      uncertainties surrounding legislation on the use of information would be helpful
      to clinicians.

PMID- 18055883
TI  - Barriers and facilitators to the implementation of the collaborative method:
      reflections from a single site.
AB  - BACKGROUND: A collaborative is an effective method of implementing evidence-based
      practice across multiple sites through the sharing of experience and knowledge of
      others in a similar setting, over a short period of time. Collaborative methods
      were first used in the USA but have been adopted internationally. AIM: This paper
      sought to document the facilitators and barriers to the implementation of the
      collaborative method, based on a single site's experience of participating in a
      multisite, state-wide heart failure collaborative. METHOD: Qualitative data was
      collected using three complementary METHODS: participant observation, reflective
      journalling and key informant interviews. Quantitative monitoring of team
      performance occurred monthly according to prespecified performance indicators.
      FINDINGS: Barriers and facilitators that were identified by this study included:
      organisational factors, team composition, dynamics and networking, changing
      doctor behaviour, clinical leadership and communication. CONCLUSION: The findings
      from this study underscore the importance of leadership, communication and team
      cohesion for the successful implementation of the collaborative method at
      individual sites. In addition, the importance of a preparatory stage that deals
      with known barriers and facilitators to the collaborative method before the
      commencement of the official study period was highlighted. The potential for the
      collaborative approach to improve clinical outcomes warrants further systematic
      evaluation of process issues and consideration of the barriers and facilitators
      to implementation in various settings.

PMID- 18055884
TI  - Evaluating the clinical appropriateness of nurses' prescribing practice: method
      development and findings from an expert panel analysis.
AB  - BACKGROUND: The number of nurses independently prescribing medicines in England
      is rising steadily. There had been no attempt systematically to evaluate the
      clinical appropriateness of nurses' prescribing decisions. AIMS: (i) To establish
      a method of assessing the clinical appropriateness of nurses' prescribing
      decisions; (ii) to evaluate the prescribing decisions of a sample of nurses,
      using this method. METHOD: A modified version of the Medication Appropriateness
      Index (MAI) was developed, piloted and subsequently used by seven medical
      prescribing experts to rate transcripts of 12 nurse prescriber consultations
      selected from a larger database of 118 audio-recorded consultations collected as
      part of a national evaluation. Experts were also able to give written qualitative
      comments on each of the MAI dimensions applied to each of the consultations.
      ANALYSIS: Experts' ratings were analysed using descriptive statistics.
      Qualitative comments were subjected to a process of content analysis to identify
      themes within and across both MAI items and consultations. RESULTS: Experts'
      application of the modified MAI to transcripts of nurse prescriber consultations
      demonstrated validity and feasibility as a method of assessing the clinical
      appropriateness of nurses' prescribing decisions. In the majority of assessments
      made by the expert panel, nurses' prescribing decisions were rated as clinically
      appropriate on all nine items in the MAI. CONCLUSION: A valid and feasible method
      of assessing the clinical appropriateness of nurses' prescribing practice has
      been developed using a modified MAI and transcripts of audio-recorded
      consultations sent to a panel of prescribing experts. Prescribing nurses in this
      study were generally considered to be making clinically appropriate prescribing
      decisions. This approach to measuring prescribing appropriateness could be used
      as part of quality assurance in routine practice, as a method of identifying
      continuing professional development needs, or in future research as the expansion
      of non-medical prescribing continues.

PMID- 18055885
TI  - Educational quality improvement report: outcomes from a revised morbidity and
      mortality format that emphasised patient safety.
AB  - PROBLEM: Although morbidity and mortality conferences (MMCs) are meant to promote
      quality care through careful analysis of adverse events, focus on individual
      actions or the fear of incrimination may interfere with identification of system
      issues contributing to the adverse outcomes. DESIGN: Participant attitudes before
      and after the intervention towards patient safety and conference redesign were
      assessed using an attitudinal survey. A list of contributing factors, recommended
      solutions and targeted system improvements was maintained with ongoing progress
      recorded. SETTING: Department of Internal Medicine training programme at
      University of Missouri-Columbia. PARTICIPANTS: Residents and fellows from the
      above residency programme. EDUCATIONAL OBJECTIVES: (1) Distinguish between
      culture of blame/shame and patient safety culture, (2) identify gaps in quality
      contributing to adverse outcomes (3) identify strategies to close gaps and (4)
      participate in root cause analysis, demonstrating an ability to review an adverse
      event and recommend an action plan. STRATEGIES FOR CHANGE: An interdisciplinary
      team modified the internal medicine MMC to emphasise a better understanding of
      patient safety principles and system-based practice interventions. For each
      adverse event analysed, root causes were identified, followed by discussion of
      system interventions that might prevent future such events. KEY MEASURES FOR
      IMPROVEMENT: (1) Attitudes of residents and fellows regarding patient safety, as
      measured on a 20-item, five-point ordinal scale survey, (2) system improvements
      generated from the patient safety MMC (PSMMC) and (3) attendance at PSMMC.
      EFFECTS OF CHANGE: Clinical outcomes: 121 system improvement recommendations were
      made and 39 were pursued on the basis of likelihood of achieving high impact
      changes. 23 improvements were implemented, 11 were partially implemented or in
      progress, and 5 were abandoned due to impracticality or redundancy. Educational
      outcomes: 58 residents and fellows completed surveys before and after
      modification of conference format. 6/20 survey items showed substantial change
      with four of these changes occurring in the desired direction. Eleven of the
      remaining 14 responses changed in the desired direction. Average MMC attendance
      increased from 41+/-8 to 50+/-10 participants (p<0.03). LESSONS LEARNT: The new
      PSMMC initiated multiple improvements in the quality of patient care without
      sacrificing attendance or attitudes of the residents or fellows. The new PSMMC
      promotes opportunities for participants to improve quality of patient care in a
      safe and nurturing environment.

PMID- 18055886
TI  - Surgical adverse outcomes and patients' evaluation of quality of care: inherent
      risk or reduced quality of care?
AB  - BACKGROUND: Previous research has shown that sicker patients are less satisfied
      with their healthcare, but specific effects of adverse health outcomes have not
      been investigated. The present study aimed to assess whether patients who
      experience adverse outcomes, in hospital or after discharge, differ in their
      evaluation of quality of care compared with patients without adverse outcomes.
      METHOD: In hospital adverse outcomes were prospectively recorded by surgeons and
      surgical residents as part of routine care. Four weeks after discharge, patients
      were interviewed by telephone about the occurrence of post-discharge adverse
      outcomes, and their overall evaluation of quality of hospital care and specific
      suggestions for improvements in the healthcare provided. RESULTS: Of 2145
      surgical patients admitted to the Leiden University Medical Center in 2003, 1876
      (88%) agreed to be interviewed. Overall evaluation was less favourable by
      patients who experienced post-discharge adverse outcomes only (average 19%
      lower). These patients were also more often dissatisfied (OR 2.02, 95% CI 1.24 to
      3.31) than patients without adverse outcomes, and they more often suggested that
      improvements were needed in medical care (OR 2.07, 1.45 to 2.95) and that
      patients were discharged too early (OR 3.26, 1.72 to 6.20). The effect of in
      hospital adverse outcomes alone was not statistically significant. Patients with
      both in hospital and post-discharge adverse outcomes also found the quality of
      care to be lower (on average 33% lower) than patients without adverse outcomes.
      CONCLUSIONS: Post-discharge adverse outcomes negatively influence patients'
      overall evaluation of quality of care and are perceived as being discharged too
      early, suggesting that patients need better information at discharge.

PMID- 18055887
TI  - Extent, nature and consequences of adverse events: results of a retrospective
      casenote review in a large NHS hospital.
AB  - OBJECTIVES: To estimate the extent, nature and consequences of adverse events in
      a large National Health Service (NHS) hospital, and to evaluate the reliability
      of a two-stage casenote review method in identifying adverse events. DESIGN: A
      two-stage structured retrospective patient casenote review. SETTING: A large NHS
      hospital in England. POPULATION: A random sample of 1006 hospital admissions
      between January and May 2004: surgery (n = 311), general medicine (n = 251),
      elderly (n = 184), orthopaedics (n = 131), urology (n = 61) and three other
      specialties (n = 68). MAIN OUTCOME MEASURES: Proportion of admissions with
      adverse events, the proportion of preventable adverse events, and the types and
      consequences of adverse events. RESULTS: 8.7% (n = 87) of the 1006 admissions had
      at least one adverse event (95% CI 7.0% to 10.4%), of which 31% (n = 27) were
      preventable. 15% of adverse events led to impairment or disability which lasted
      more than 6 months and another 10% contributed to patient death. Adverse events
      led to a mean increased length of stay of 8 days (95% CI 6.5 to 9). The
      sensitivity of the screening criteria in identifying adverse events was 92% (95%
      CI 87% to 96%) and the specificity was 62% (95% CI 53% to 71%). Inter-rater
      reliability for determination of adverse events was good (kappa = 0.64), but for
      the assessment of preventability it was only moderate (kappa = 0.44). CONCLUSION:
      This study confirms that adverse events are common, serious and potentially
      preventable source of harm to patients in NHS hospitals. The accuracy and
      reliability of a structured two-stage casenote review in identifying adverse
      events in the UK was confirmed.

PMID- 18055888
TI  - European Surveillance of Antimicrobial Consumption (ESAC): quality indicators for
      outpatient antibiotic use in Europe.
AB  - BACKGROUND AND OBJECTIVE: Indicators to measure the quality of healthcare are
      increasingly used by healthcare professionals and policy makers. In the context
      of increasing antimicrobial resistance, this study aimed to develop valid drug
      specific quality indicators for outpatient antibiotic use in Europe, derived from
      European Surveillance of Antimicrobial Consumption (ESAC) data. METHODS: 27
      experts (15 countries), in a European Science Foundation workshop, built on the
      expertise within the European Drug Utilisation Research Group, the General
      Practice Respiratory Infections Network, the ESCMID Study Group on Primary Care
      Topics, the Belgian Antibiotic Policy Coordination Committee, the World Health
      Organization, ESAC, and other experts. A set of proposed indicators was developed
      using 1997-2003 ESAC data. Participants scored the relevance of each indicator to
      reducing antimicrobial resistance, patient health benefit, cost effectiveness and
      public health policy makers (scale: 1 (completely disagree) to 9 (completely
      agree)). The scores were processed according to the UCLA-RAND appropriateness
      method. Indicators were judged relevant if the median score was not in the 1-6
      interval and if there was consensus (number of scores within the 1-3 interval was
      fewer than one third of the panel). From the relevant indicators providing
      overlapping information, the one with the highest scores was selected for the
      final set of quality indicators-values were updated with 2004 ESAC data. RESULTS:
      22 participants (12 countries) completed scoring of a set of 22 proposed
      indicators. Nine were rated as relevant antibiotic prescribing indicators on all
      four dimensions; five were rated as relevant if only relevance to reducing
      antimicrobial resistance and public health policy makers was taken into account.
      A final set of 12 indicators was selected. CONCLUSION: 12 of the proposed ESAC
      based quality indicators for outpatient antibiotic use in Europe have face
      validity and are potentially applicable. These indicators could be used to better
      describe antibiotic use in ambulatory care and assess the quality of national
      antibiotic prescribing patterns in Europe.

PMID- 18055889
TI  - Differences in the quality of primary medical care services by remoteness from
      urban settlements.
AB  - OBJECTIVE: To examine if the quality of primary medical care varies with
      remoteness from urban settlements. DESIGN: Cross-sectional analysis of publicly
      available data of 18 process and intermediate outcome measures for people with
      coronary heart disease (CHD), diabetes and stroke. SETTING AND PARTICIPANTS:
      Populations registered with 912 general practices in Scotland grouped into three
      categories by level of remoteness from urban settlements: not remote, remote and
      very remote. MAIN OUTCOME MEASURES: Mean percentages achieving quality indicators
      and interquartile range scores. RESULTS: Remote and very remote practices were
      more likely to have characteristics associated with low Quality and Outcomes
      Framework (QOF) total points score (smaller, higher capitation income, dispensing
      practice, and had lower statin prescribing despite higher prevalence of
      cardiovascular disease and diabetes). However, in contrast with previous
      research, there was little evidence that quality of care was lower in more remote
      areas for the 18 process and intermediate outcome measures examined. The
      exception was significantly lower cholesterol measurement and control in people
      with CHD, diabetes and stroke attending very remote practices (p<0.01) and beta
      blocker prescription in CHD (p = 0.01). CONCLUSIONS: Under QOF, there are few
      differences in the quality of care delivered to patients in practices with
      different degrees of remoteness. The differences in achievement for cholesterol
      were consistent with lower rates of statin prescribing relative to disease burden
      in very remote practices. No differences were found for complex process measures
      such as retinopathy screening, implying that differences under QOF are more
      likely to be due to slower adoption of evidence-based practice than access
      problems. Examining this will require analysis of individual patient data.

PMID- 18055890
TI  - Comparison of patients' assessments of the quality of stroke care with audit
      findings.
AB  - OBJECTIVE: To determine the extent of correlation between stroke patients'
      experiences of hospital care with the quality of services assessed in a national
      audit. METHODS: Patients' assessments of their care derived from survey data were
      linked to data obtained in the National Sentinel Stroke Audit 2004 for 670
      patients in 51 English NHS trusts. A measure of patients' experience of hospital
      stroke care was derived by summing responses to 31 survey items and grouping
      these into three broad concept domains: quality of care; information; and
      relationships with staff. Audit data were extracted from hospital admissions data
      and management information to assess the organisation of services, and obtained
      retrospectively from patient records to evaluate the delivery of care. Patient
      survey responses were compared with audit measures of organisation of care and
      compliance with clinical process standards. RESULTS: Patient experience scores
      were positively correlated with clinicians' assessment of the organisational
      quality of stroke care, but were largely unrelated to clinical process standards.
      Responses to individual questions regarding communication about diagnosis
      revealed a discrepancy between clinicians' and patients' reports. CONCLUSIONS:
      Better organised stroke care is associated with more positive patient
      experiences. Examining areas of disparity between patients' and clinicians'
      reports is important for understanding the complex nature of healthcare and for
      identifying areas for quality improvement. Future evaluations of the quality of
      stroke services should include a validated patient experience survey in addition
      to audit of clinical records.

PMID- 18055891
TI  - Impact of short evidence summaries in discharge letters on adherence of
      practitioners to discharge medication. A cluster-randomised controlled trial.
AB  - BACKGROUND: International concern about quality of medical care has led to
      intensive study of interventions to ensure care is consistent with best evidence.
      Simple, inexpensive, feasible and effective interventions remain limited.
      OBJECTIVE: We examined the impact of one-sentence evidence summaries appended to
      consultants' letters to primary care practitioners on adherence of the
      practitioners to recommendations made by the consultants regarding medication for
      patients with chronic medical problems. DESIGN: Cluster-randomised trial.
      SETTING: Secondary/primary care interface (urban district hospital/referral
      practices). PARTICIPANTS: 178 practices received one or more discharge letters
      with evidence summaries. The 66 practices in the intervention group provided
      feedback on 172 letters, and the 56 practices in the control group provided
      feedback on 96 letters. RESULTS: Appending an evidence summary to discharge
      letters resulted in a decrease in non-adherence to discharge medication from
      29.6% to 18.5% (difference adjusted for underlying medical condition 12.5%; p =
      0.039). Among the five possible reasons for discontinuing discharge medication,
      the evidence summaries seemed to have the largest impact on budget-related
      reasons for discontinuation (2.6% in the intervention versus 10.7% in the control
      group (p = 0.052)). Most clinicians (72%) were enthusiastic about continuing
      receiving evidence summaries with discharge letters in routine care. CONCLUSIONS:
      The one-sentence evidence summary is a simple, inexpensive, well-accepted
      intervention that may improve primary care practitioners' adherence to evidence
      based consultant recommendations.

PMID- 18055892
TI  - Capturing users' experience of UK out-of-hours primary medical care: piloting and
      psychometric properties of the Out-of-hours Patient Questionnaire.
AB  - BACKGROUND AND OBJECTIVE: Provision of out-of-hours care in the UK National
      Health Service (NHS) has changed in recent years with new models of provision and
      the introduction of national quality requirements. Existing survey instruments
      tend to focus on users' satisfaction with service provision; most were developed
      without undertaking supporting qualitative fieldwork. In this study, a survey
      instrument was developed taking account of these changes in service provision and
      undertaking supporting qualitative fieldwork. This paper reports on the
      development and psychometric properties of the new survey instrument, the Out-of
      hours Patient Questionnaire (OPQ), which aims to capture information on the
      entirety of users' experiences of out-of-hours care, from the decision to make
      contact through to completion of their care management. METHODS: An iterative
      approach was undertaken to develop the new instrument which was then tested in
      users of out-of-hours services in three geographically distributed UK settings.
      For the purposes of this study, "service users" were defined as "individuals
      about whom contact was made with an out-of-hours primary care medical service",
      whether that contact was made by the user themselves, or via a third party.
      Analysis was undertaken of the acceptability, reliability and validity of the
      survey instrument. RESULTS: The OPQ tested is a 56-item questionnaire, which was
      distributed to 1250 service users. Respondents were similar in respect of gender,
      but were older and more affluent (using a proxy measure) than non-respondents.
      Item completion rates were acceptable. Respondents sometimes completed sections
      of the questionnaire which did not equate to their principal mode of management
      as recorded in the record of the contact. Preliminary evidence suggests the OPQ
      is a valid and reliable instrument which contains within it two discrete scales-
      a consultation satisfaction scale (nine items) and an "entry-access" scale (four
      items). Further work is required to determine the generalisability of findings
      obtained following use of the OPQ, especially to non-white user populations.
      CONCLUSION: The OPQ is an acceptable instrument for capturing information on
      users' experiences of out-of-hours care. Preliminary evidence suggests it is both
      valid and reliable in use. Further work will report on its utility in informing
      out-of-hours service planning and configuration and standard-setting in relation
      to UK national quality requirements.

PMID- 18055893
TI  - Exploring users' experiences of accessing out-of-hours primary medical care
      services.
AB  - BACKGROUND: Since 2000, out-of-hours primary medical care services in the UK have
      undergone major changes in the organisation and delivery of services in response
      to recommendations by the Carson Review and more recently, through the new
      General Medical Services Contract (GMS2). People calling their general practice
      in the evening or at weekends are redirected to the out-of-hours service which
      may offer telephone advice, a home visit or a visit to a treatment centre. Little
      is known about users' experiences under the new arrangements. AIM: To explore
      users' experiences of out-of-hours primary medical care. DESIGN OF STUDY: A
      qualitative study employing focus groups and telephone interviews. SETTING: Three
      out-of-hours primary medical care service providers in England. METHODS: Focus
      groups and telephone interviews were conducted with 27 recent users of out-of
      hours services. RESULTS: Key areas of concern included the urgency with which
      cases are handled, and delays when waiting for a call back or home visit. Users
      felt that providers were reluctant to do home visits. The service was regarded as
      under-resourced and frequently misused. Many expressed anxiety about calling,
      feeling unsure about how appropriate their call was and many were uncertain about
      how the service operated. CONCLUSIONS: Service users need clear information on
      how current out-of-hours services operate and how it should be used. Problems
      with triaging need to be addressed, users should be kept informed of any delays,
      and care needs to be taken to ensure that the new arrangements do not alienate
      older people or individuals with complex health needs.

PMID- 18055894
TI  - Making the right decision: Benjamin Franklin's son dies of smallpox in 1736.

PMID- 18055895
TI  - More guidelines on research ethics?

PMID- 18055896
TI  - From cure to palliation: concept, decision and acceptance.
AB  - The aim of this paper is to present and discuss nurses' and physicians' comments
      in a questionnaire relating to patients' transition from curative treatment to
      palliative care. The four-page questionnaire relating to experiences of and
      attitudes towards communication, decision-making, documentation and
      responsibility of nurses and physicians and towards the competence of patients
      was developed and sent to a random sample of 1672 nurses and physicians of 10
      specialties. The response rate was 52% (n = 844), and over one-third made
      comments. The respondents differed in their comments about three areas: the
      concept of palliative care, experiences of unclear decision-making and
      difficulties in acceptance of the patient's situation. The responses are analysed
      in terms of four ethical theories: virtue ethics, deontology, consequentialism
      and casuistry. Many virtues considered to be appropriate for healthcare personnel
      to possess were invoked. Compassion, honesty, justice and prudence are especially
      important. However, principles of medical ethics, such as the deontological
      principle of respect for self-determination and the consequence of avoidance of
      harm, are also implied. Casuistry may be particularly helpful in analysing
      certain areas of difficulty-namely, what is meant by "palliative care", decision
      making and accepting the patient's situation. Keeping a patient in a state of
      uncertainty often causes more suffering than necessary. Communication among the
      staff and with patients must be explicit. Many of the staff have not had adequate
      training in communicating with patients who are at the end of their life. Time
      for joint reflection has to be regained, and training in decision-making is
      essential. In our opinion, palliative care in Sweden is in need of improvement.

PMID- 18055897
TI  - Do patients have duties?
AB  - The notion of patients' duties has received periodic scholarly attention but
      remains overwhelmed by attention to the duties of healthcare professionals. In a
      previous paper the author argued that patients in publicly funded healthcare
      systems have a duty to participate in clinical research, arising from their debt
      to previous patients. Here the author proposes a greatly extended range of
      patients' duties grounding their moral force distinctively in the interests of
      contemporary and future patients, since medical treatment offered to one patient
      is always liable to be an opportunity cost (however justifiable) in terms of
      medical treatment needed by other patients. This generates both negative and
      positive duties. Ten duties-enjoining obligations ranging from participation in
      healthcare schemes to promoting one's own earliest recovery from illness-are
      proposed. The characteristics of these duties, including their basis, moral
      force, extent and enforceability, are considered. They are tested against a range
      of objections-principled, societal, epistemological and practical-and found to
      survive. Finally, the paper suggests that these duties could be thought to
      reinforce a regrettably adversarial characteristic, shared with rights-based
      approaches, and that a preferable alternative might be sought through the (here
      unexplored) notion of a "virtuous patient" contributing to a problem-solving
      partnership with the clinician. However, in defining and giving content to that
      partnership, there is a clear role for most, if not all, of the proposed duties;
      their value thus extends beyond the adversarial context in which they might first
      be thought to arise.

PMID- 18055898
TI  - A software platform to analyse the ethical issues of electronic patient privacy
      policy: the S3P example.
AB  - Paper-based privacy policies fail to resolve the new changes posed by electronic
      healthcare. Protecting patient privacy through electronic systems has become a
      serious concern and is the subject of several recent studies. The shift towards
      an electronic privacy policy introduces new ethical challenges that cannot be
      solved merely by technical measures. Structured Patient Privacy Policy (S3P) is a
      software tool assuming an automated electronic privacy policy in an electronic
      healthcare setting. It is designed to simulate different access levels and rights
      of various professionals involved in healthcare in order to assess the emerging
      ethical problems. The authors discuss ethical issues concerning electronic
      patient privacy policies that have become apparent during the development and
      application of S3P.

PMID- 18055899
TI  - The Declaration of Sydney on human death.
AB  - On 5 August 1968, publication of the Harvard Committee's report on the subject of
      "irreversible coma" established a standard for diagnosing death on neurological
      grounds. On the same day, the 22nd World Medical Assembly met in Sydney,
      Australia, and announced the Declaration of Sydney, a pronouncement on death,
      which is less often quoted because it was overshadowed by the impact of the
      Harvard Report. To put those events into present-day perspective, the authors
      reviewed all papers published on this subject and the World Medical Association
      web page and documents, and corresponded with Dr A G Romualdez, the son of Dr A Z
      Romualdez. There was vast neurological expertise among some of the Harvard
      Committee members, leading to a comprehensible and practical clinical description
      of the brain death syndrome and the way to diagnose it. This landmark account had
      a global medical and social impact on the issue of human death, which
      simultaneously lessened reception of the Declaration of Sydney. Nonetheless, the
      Declaration of Sydney faced the main conceptual and philosophical issues on human
      death in a bold and forthright manner. This statement differentiated the meaning
      of death at the cellular and tissue levels from the death of the person. This was
      a pioneering view on the discussion of human death, published as early as in
      1968, that should be recognised by current and future generations.

PMID- 18055900
TI  - The secret art of managing healthcare expenses: investigating implicit rationing
      and autonomy in public healthcare systems.
AB  - Rationing healthcare is a difficult task, which includes preventing patients from
      accessing potentially beneficial treatments. Proponents of implicit rationing
      argue that politicians cannot resist pressure from strong patient groups for
      treatments and conclude that physicians should ration without informing patients
      or the public. The authors subdivide this specific programme of implicit
      rationing, or "hidden rationing", into local hidden rationing, unsophisticated
      global hidden rationing and sophisticated global hidden rationing. They evaluate
      the appropriateness of these methods of rationing from the perspectives of
      individual and political autonomy and conclude that local hidden rationing and
      unsophisticated global hidden rationing clearly violate patients' individual
      autonomy, that is, their right to participate in medical decision-making. While
      sophisticated global hidden rationing avoids this charge, the authors point out
      that it nonetheless violates the political autonomy of patients, that is, their
      right to engage in public affairs as citizens. A defence of any of the forms of
      hidden rationing is therefore considered to be incompatible with a defence of
      autonomy.

PMID- 18055901
TI  - French district nurses' opinions towards euthanasia, involvement in end-of-life
      care and nurse patient relationship: a national phone survey.
AB  - OBJECTIVES: To assess French district nurses' opinions towards euthanasia and to
      study factors associated with these opinions, with emphasis on attitudes towards
      terminal patients. DESIGN AND SETTING: An anonymous telephone survey carried out
      in 2005 among a national random sample of French district nurses. PARTICIPANTS:
      District nurses currently delivering home care who have at least 1 year of
      professional experience. Of 803 district nurses contacted, 602 agreed to
      participate (response rate 75%). MAIN OUTCOME MEASURES: Opinion towards the
      legalisation of euthanasia (on a five-point Likert scale from "strongly agree" to
      "strongly disagree"), attitudes towards terminal patients (discussing end-of-life
      issues with them, considering they should be told their prognosis, valuing the
      role of advance directives and surrogates). RESULTS: Overall, 65% of the 602
      nurses favoured legalising euthanasia. Regarding associated factors, this
      proportion was higher among those who discuss end-of-life issues with terminal
      patients (70%), who consider competent patients should always be told their
      prognosis (81%) and who value the role of advance directives and surrogates in
      end-of-life decision-making for incompetent patients (68% and 77% respectively).
      Women and older nurses were less likely to favour legalising euthanasia, as were
      those who believed in a god who masters their destiny. CONCLUSIONS: French nurses
      are more in favour of legalising euthanasia than French physicians; these two
      populations contrast greatly in the factors associated with this support. Further
      research is needed to investigate how and to what extent such attitudes may
      affect nursing practice and emotional well-being in the specific context of end
      of-life home care.

PMID- 18055902
TI  - Elderly patients also have rights.
AB  - BACKGROUND: Sharing information with relatives of elderly patients in primary
      care and in hospital has to fit into the complex set of obligations,
      justifications and pressures concerning the provision of information, and the
      results of some studies point to the need for further empirical studies exploring
      issues of patient autonomy, privacy and informed consent in the day-to-day care
      of older people. OBJECTIVES: To know the frequency with which "capable" patients
      over 65 years of age receive information when admitted to hospital, the
      information offered to the families concerned, the person who gives consent for
      medical intervention, and the degree of satisfaction with the information
      received and the healthcare provided. METHOD: A descriptive questionnaire given
      to 200 patients and 200 relatives during the patients' stay in hospital. RESULTS:
      Only 5% of patients confirmed that they had been asked whether information could
      be given to their relatives. A significantly higher proportion of relatives
      received information on the successive stages of the care offered than did
      patients themselves. As the age of the patients increased, so the number who were
      given information, understood the information and were asked for their consent
      for complementary tests decreased. The degree of satisfaction with the
      information offered was high for both patients and relatives (86.5% and 84%,
      respectively), despite the irregularities observed. CONCLUSIONS: The capacity of
      elderly patients to participate in the decision-making process is frequently
      doubted simply because they have reached a certain age and it is thought that
      relatives should act as their representatives. In Spain, the opinion of the
      family and doctors appears to play a larger role in making decisions than does
      the concept of patient autonomy.

PMID- 18055903
TI  - Ethical reflection on the harm in reproductive decision-making.
AB  - Advances in reproductive technologies continue to present ethical problems
      concerning their implementation and use. These advances have preoccupied
      bioethicists in their bid to gauge our moral responsibilities and obligations
      when making reproductive decisions. The aim of this discussion is to highlight
      the importance of a sensibility to differences in moral perspective as part of
      our ethical inquiry in these matters. Its focal point is the work of John
      Harris(i), who has consistently addressed the ethical issues raised by advancing
      reproductive technologies. The discussion is aimed at a central tenet of Harris's
      position on reproductive decision-making-namely, that in some instances, giving
      birth to a worthwhile life may cause harm and will therefore be morally wrong. It
      attempts to spell out some of the implications of Harris's position that the
      author takes to involve a misplaced generality. To support this claim, some
      examples are explored that demonstrate the variety of ways in which concepts
      (such as harm) may manifest themselves as moral considerations within the context
      of reproductive decision-making. The purpose is to demonstrate that Harris's
      general conception of the moral limits of reproductive autonomy obscures the
      issues raised by particular cases, which in themselves may reveal important
      directions for our ethical inquiry.

PMID- 18055904
TI  - End-of-life decisions in medical practice: a survey of doctors in Victoria
      (Australia).
AB  - OBJECTIVES: To discover the current state of opinion and practice among doctors
      in Victoria, Australia, regarding end-of-life decisions and the legalisation of
      voluntary euthanasia. Longitudinal comparison with similar 1987 and 1993 studies.
      DESIGN AND PARTICIPANTS: Cross-sectional postal survey of doctors in Victoria.
      RESULTS: 53% of doctors in Victoria support the legalisation of voluntary
      euthanasia. Of doctors who have experienced requests from patients to hasten
      death, 35% have administered drugs with the intention of hastening death. There
      is substantial disagreement among doctors concerning the definition of
      euthanasia. CONCLUSIONS: Disagreement among doctors concerning the meaning of the
      term euthanasia may contribute to misunderstanding in the debate over voluntary
      euthanasia. Among doctors in Victoria, support for the legalisation of voluntary
      euthanasia appears to have weakened slightly over the past 17 years. Opinion on
      this issue is sharply polarised.

PMID- 18055905
TI  - The stem cell debate continues: the buying and selling of eggs for research.
AB  - Now that stem cell scientists are clamouring for human eggs for cloning-based
      stem cell research, there is vigorous debate about the ethics of paying women for
      their eggs. Generally speaking, some claim that women should be paid a fair wage
      for their reproductive labour or tissues, while others argue against the further
      commodification of reproductive labour or tissues and worry about voluntariness
      among potential egg providers. Siding mainly with those who believe that women
      should be financially compensated for providing eggs for research, the new stem
      cell guidelines of the International Society for Stem Cell Research (ISSCR)
      legitimise both reimbursement of direct expenses and financial compensation for
      many women who supply eggs for research. In this paper, the authors do not
      attempt to resolve the thorny issue of whether payment for eggs used in human
      embryonic stem cell research is ethically legitimate. Rather, they want to show
      specifically that the ISSCR recommended payment practices are deeply flawed and,
      more generally, that all payment schemes that aim to avoid undue inducement of
      women risk the global exploitation of economically disadvantaged women.

PMID- 18055906
TI  - Ethics committees and the legality of research.
AB  - One role of research ethics committees (RECs) is to assess the ethics of proposed
      health research. In some countries, RECs are also instructed to assess its
      legality. However, in other countries they are explicitly instructed not to do
      so. In this paper, I defend the claim that public policy should instruct RECs not
      to assess the legality of proposed research ("the Claim"). I initially defend a
      presumption in favour of the Claim, citing reasons for making research
      institutions solely responsible for assessing the legality of their own research.
      I then consider three arguments against the Claim which may over-ride this
      presumption-namely, that policy should instruct RECs to assess the legality of
      research because (1) doing so would minimise the costs of assessing the legality
      of research, (2) whether research is legal may partly determine whether it is
      ethical and (3) whether research is legal may constitute evidence for whether it
      is ethical. I reject the first two arguments and note that whether the third
      succeeds depends on the answer to a more fundamental question about the
      appropriate nature of REC ethical deliberation. I end with a brief discussion of
      this question, tentatively concluding that the third argument also fails.

PMID- 18055907
TI  - Teaching medical students about fair distribution of healthcare resources.
AB  - Healthcare package decisions are complex. Different judgements about
      effectiveness, cost-effectiveness and disease burden influence the decision
      making process. Moreover, different concepts of justice generate different ideas
      about fair distribution of healthcare resources. This paper presents a decision
      model that is used in medical school in order to familiarise medical students
      with the different concepts of justice and the ethical dimension of making
      concrete choices. The model is based on the four-stage decision model developed
      in the Netherlands by the Dunning Committee and the discussion that followed its
      presentation in 1991. Having to deal with 10 medical services, students working
      with the model learn to discern and integrate four different ideas of
      distributive justice that are integrated in a flow chart: libertarian,
      communitarian, egalitarian and utilitarian.

PMID- 18055909
TI  - GATA4 sequence variants in patients with congenital heart disease.
AB  - BACKGROUND: Recent reports have identified mutations in the transcription factor
      GATA4 in familial cases of cardiac septal defects. The prevalence of GATA4
      mutations in the population of patients with septal defects is unknown. Given
      that patients with septal and conotruncal defect can share a common genetic
      basis, it is unclear whether patients with additional types of CHD might also
      have GATA4 mutations. AIMS: To explore these questions by investigating a large
      population of 628 patients with either septal or conotruncal defects for GATA4
      sequence variants. METHODS: The GATA4 coding region and exon-intron boundaries
      were investigated for sequence variants using denaturing high-performance liquid
      chromatography or conformation-sensitive gel electrophoresis. Samples showing
      peak or band shifts were reamplified from genomic DNA and sequenced. RESULTS:
      Four missense sequence variants (Gly93Ala, Gln316Glu, Ala411Val, Asp425Asn) were
      identified in five patients (two with atrial septal defect, two with ventricular
      septal defect and one with tetralogy of Fallot), which were not seen in a control
      population. All four affected amino acid residues are conserved across species,
      and two of the sequence variants lead to changes in polarity. Ten synonymous
      sequence variants were also identified in 18 patients, which were not seen in the
      control population. CONCLUSIONS: These data suggest that non-synonymous GATA4
      sequence variants are found in a small percentage of patients with septal defects
      and are very uncommonly found in patients with conotruncal defects.

PMID- 18055910
TI  - Episodic ataxia and hemiplegia caused by the 8993T->C mitochondrial DNA mutation.
AB  - The m.8993T-->C MTATP6 mutation of mitochondrial DNA (mtDNA) usually causes
      mitochondrial disease in childhood, but was recently described in a family with
      adult onset ataxia and polyneuropathy. Cytochrome c oxidase muscle
      histochemistry, which is the standard clinical investigation for mitochondrial
      disease in adults, is usually normal in patients with MTATP6 mutations. This
      raises the possibility that these cases have been missed in the past. We
      therefore studied 308 patients with unexplained ataxia and 96 patients with
      suspected Charcot-Marie-Tooth disease to determine whether the m.8993T-->C MTATP6
      mutation is common in unexplained inherited ataxia and/or polyneuropathy. We
      identified a three-generation family with the m.8993T-->C mutation of mtDNA. One
      subject had episodic ataxia (EA) and transient hemipareses, broadening the
      phenotype. However, no further cases were identified in an additional cohort of
      191 patients with suspected EA. In conclusion, m.8993T-->C MTATP6 should be
      considered in patients with unexplained ataxia, CMT or EA, but cases are
      uncommon.

PMID- 18055911
TI  - Deletions of NF1 gene and exons detected by multiplex ligation-dependent probe
      amplification.
AB  - To estimate the contribution of single and multi-exon NF1 gene copy-number
      changes to the NF1 mutation spectrum, we analysed a series of 201 Italian
      patients with neurofibromatosis type 1 (NF1). Of these, 138 had previously been
      found, using denaturing high-performance liquid chromatography or protein
      truncation test, to be heterozygous for intragenic NF1 point
      mutations/deletions/insertions, and were excluded from this analysis. The
      remaining 63 patients were analysed using multiplex ligation-dependent probe
      amplification (MLPA), which allows detection of deletions or duplications
      encompassing >or=1 NF1 exons, as well as entire gene deletions. MLPA results were
      validated using real-time quantitative PCR (qPCR) or fluorescent in situ
      hybridisation. MLPA screening followed by real-time qPCR detected a total of 23
      deletions. Of these deletions, six were single exon, eight were multi-exon, and
      nine were of the entire NF1 gene. In our series, deletions encompassing >or=1 NF1
      exons accounted for approximately 7% (14/201) of the NF1 gene mutation spectrum,
      suggesting that screening for these should now be systematically included in
      genetic testing of patients with NF1.

PMID- 18055912
TI  - Combination of two regulatory elements in the Tetrahymena thermophila HSP70-1
      gene controls heat shock activation.
AB  - The induction of heat shock genes (HSPs) is thought to be primarily regulated by
      heat shock transcription factors (HSFs), which bind target sequences on HSP
      promoters, called heat shock elements (HSEs). In this study, we investigated the
      5' untranslated regions of the Tetrahymena thermophila HSP70-1 gene, and we
      found, in addition to the canonical and divergent HSEs, multiple sets of GATA
      elements that have not been reported previously in protozoa. By means of in vivo
      analysis of a green fluorescent protein reporter transgene driven by the HSP70-1
      promoter, we demonstrate that HSEs do not represent the minimal regulatory
      elements for heat shock induction, since the HSP70-1 is tightly regulated by both
      HSE and GATA elements. Electrophoretic mobility shift assay also showed that HSFs
      are constitutively bound to the HSEs, whereas GATA elements are engaged only
      after heat shock. This is the first demonstration by in vivo analysis of
      functional HSE and GATA elements in protozoa. Furthermore, we provide evidence of
      a functional link between HSE and GATA elements in the activation of the heat
      shock response.

PMID- 18055913
TI  - Pathway of cytosolic starch synthesis in the model glaucophyte Cyanophora
      paradoxa.
AB  - The nature of the cytoplasmic pathway of starch biosynthesis was investigated in
      the model glaucophyte Cyanophora paradoxa. The storage polysaccharide granules
      are shown to be composed of both amylose and amylopectin fractions, with a chain
      length distribution and crystalline organization similar to those of green algae
      and land plant starch. A preliminary characterization of the starch pathway
      demonstrates that Cyanophora paradoxa contains several UDP-glucose-utilizing
      soluble starch synthase activities related to those of the Rhodophyceae. In
      addition, Cyanophora paradoxa synthesizes amylose with a granule-bound starch
      synthase displaying a preference for UDP-glucose. A debranching enzyme of
      isoamylase specificity and multiple starch phosphorylases also are evidenced in
      the model glaucophyte. The picture emerging from our biochemical and molecular
      characterizations consists of the presence of a UDP-glucose-based pathway similar
      to that recently proposed for the red algae, the cryptophytes, and the
      alveolates. The correlative presence of isoamylase and starch among
      photosynthetic eukaryotes is discussed.

PMID- 18055914
TI  - MOS1 osmosensor of Metarhizium anisopliae is required for adaptation to insect
      host hemolymph.
AB  - Entomopathogenic fungi such as Metarhizium anisopliae infect insects by direct
      penetration of the cuticle, after which the fungus adapts to the high osmotic
      pressure of the hemolymph and multiplies. Here we characterize the M. anisopliae
      Mos1 gene and demonstrate that it encodes the osmosensor required for this
      process. MOS1 contains transmembrane regions and a C-terminal Src homology 3
      domain similar to those of yeast osmotic adaptor proteins, and homologs of MOS1
      are widely distributed in the fungal kingdom. Reverse transcription-PCR
      demonstrated that Mos1 is up-regulated in insect hemolymph as well as artificial
      media with high osmotic pressure. Transformants containing an antisense vector
      directed to the Mos1 mRNA depleted transcript levels by 80%. This produced
      selective alterations in regulation of genes involved in hyphal body formation,
      cell membrane stiffness, and generation of intracellular turgor pressure,
      suggesting that these processes are mediated by MOS1. Consistent with a role in
      stress responses, transcript depletion of Mos1 increased sensitivity to osmotic
      and oxidative stresses and to compounds that interfere with cell wall
      biosynthesis. It also disrupted developmental processes, including formation of
      appressoria and hyphal bodies. Insect bioassays confirmed that Mos1 knockdown
      significantly reduces virulence. Overall, our data show that M. anisopliae MOS1
      mediates cellular responses to high osmotic pressure and subsequent adaptations
      to colonize host hemolymph.

PMID- 18055915
TI  - Amt2 permease is required to induce ammonium-responsive invasive growth and
      mating in Cryptococcus neoformans.
AB  - The conserved AmtB/Mep/Rh family of proteins mediate the transport of ammonium
      across cellular membranes in a wide range of organisms. Certain fungal members of
      this group are required to initiate filamentous growth. We have investigated the
      functions of two members of the AmtB/Mep/Rh family from the pathogenic
      basidiomycete Cryptococcus neoformans. Amt1 and Amt2 are low- and high-affinity
      ammonium permeases, respectively, and a mutant lacking both permeases is unable
      to grow under ammonium-limiting conditions. AMT2 is transcriptionally induced in
      response to nitrogen limitation, whereas AMT1 is constitutively expressed. Single
      and double amt mutants exhibit wild-type virulence in two models of
      cryptococcosis. Consistent with this, the formation of two C. neoformans
      virulence factors, cell wall melanin and the extracellular polysaccharide
      capsule, is not impaired in cells lacking either or both of the Amt1 and Amt2
      permeases. Amt2 is, however, required for the initiation of invasive growth of
      haploid cells under low-nitrogen conditions and for the mating of wild-type cells
      under the same conditions. We propose that Amt2 may be a new fungal ammonium
      sensor and an element of the signaling cascades that govern the mating of C.
      neoformans in response to environmental nutritional cues.

PMID- 18055916
TI  - Surgical decompression of the quadrilateral space in overhead athletes.
AB  - BACKGROUND: Quadrilateral space syndrome is an uncommon condition that can
      disable the overhead athlete. The authors describe 4 cases of quadrilateral space
      syndrome that may assist clinicians in recognition of this problem in patients
      with posterior shoulder pain. HYPOTHESIS: Quadrilateral space syndrome can
      present as posterior shoulder pain in the overhead athlete, and surgical
      decompression can relieve symptoms and allow full return to activity. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: Between 2004 and 2006, the
      authors performed surgical decompression of the quadrilateral space in 4 overhead
      athletes (4 shoulders; mean age, 24 years). They evaluated the clinical
      presentations, diagnostic tests, surgical procedures, and results of treatment.
      Mean follow-up was 24.5 months. RESULTS: All 4 patients underwent surgical
      decompression of the quadrilateral space. Fibrous bands entrapped the axillary
      nerve in 3 shoulders, and venous dilation was found in the fourth shoulder. All
      patients returned to full activity without pain or limitation of overhead
      function 12 weeks after surgery. CONCLUSION: Quadrilateral space syndrome is an
      uncommon cause of posterior shoulder pain that is easily overlooked and can
      severely limit overhead function in the athlete. Surgical decompression can
      predictably relieve pain and improve function in patients who do not respond to
      nonoperative regimens.

PMID- 18055917
TI  - Ten- to 14-year follow-up of the Nirschl surgical technique for lateral
      epicondylitis.
AB  - BACKGROUND: Good to excellent short-term results have been reported for the
      surgical treatment of lateral epicondylitis using various surgical techniques.
      HYPOTHESIS: Surgical treatment for lateral epicondylitis using the mini-open
      Nirschl surgical technique will lead to durable results at long-term follow-up.
      STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Records from 139
      consecutive surgical procedures (130 patients) for lateral epicondylitis
      performed by 1 surgeon between 1991 and 1994 were retrospectively reviewed.
      Eighty-three patients (92 elbows) were available by telephone for a mean follow
      up of 12.6 years (range, 10-14 years). Outcome measures included the Numeric Pain
      Intensity Scale, Nirschl and Verhaar tennis elbow-specific scoring systems, and
      American Shoulder and Elbow Surgeons elbow form. Preoperative data were collected
      retrospectively. RESULTS: The mean age of the study group was 46 years (range, 23
      70 years) with 45 men and 38 women. Eighty-seven of the procedures were primary,
      and 5 were revision tennis elbow surgeries. Concomitant procedures were performed
      in 30 patients including ulnar nerve release in 24 patients, medial tennis elbow
      procedures in 23 patients, shoulder arthroscopy in 2 patients, carpal tunnel
      release in 1 patient, and triceps debridement and osteophyte excision in 1
      patient. The mean duration of preoperative symptoms was 2.2 years (range, 2
      months to 10 years). The mean Nirschl tennis elbow score improved from 23.0 to
      71.0, and the mean American Shoulder and Elbow Surgeons score improved from 34.3
      to 87.7 at a minimum of 10-year follow-up (P < .05). The Numeric Pain Intensity
      Scale pain score improved from 8.4 preoperatively to 2.1 (P < .05). Results were
      rated as excellent in 71 elbows, good in 6 elbows, fair in 9 elbows, and poor in
      6 elbows by the Nirschl tennis elbow score. By the criteria of Verhaar et al, the
      results were excellent in 45 elbows, good in 32 elbows, fair in 8 elbows, and
      poor in 7 elbows. Eighty-four percent good to excellent results were achieved
      using both scoring systems. Ninety-two percent of the patients reported normal
      elbow range of motion. The overall improvement rate was 97%. Patient satisfaction
      averaged 8.9 of 10. Ninety-three percent of those available at a minimum of 10
      year follow-up reported returning to their sports. CONCLUSION: The mini-open
      Nirschl surgical technique with accurate resection of the tendinosis tissue
      remains highly successful in the long term.

PMID- 18055918
TI  - The effects of sequential sectioning of defined posterior cruciate ligament fiber
      regions on translational knee motion.
AB  - BACKGROUND: Recent studies have shown that the posterior cruciate ligament (PCL)
      is composed of a continuum of fiber regions that display characteristic
      mechanical behavior under different motion and loading conditions. HYPOTHESIS:
      The anterior, central, and posterior fiber regions of the PCL differentially
      contribute to control of posterior translation of the tibia. STUDY DESIGN:
      Controlled laboratory study. METHODS: Nine intact, fresh-frozen cadaveric knees
      were instrumented with excursion wires implanted within the anterior, central,
      and posterior fiber regions of the PCL. In groups of 3, patterns of incremental
      posterior tibial translation using a 74-N posterior force were analyzed as a
      function of the variable linear separation distance between tibial and femoral
      fiber region attachment sites during posterior drawer testing at knee flexion
      angles of 20 degrees and 90 degrees before and after sequential fiber region
      section. RESULTS: At 20 degrees of knee flexion, there was no statistical
      difference in the relatively small amount of posterior tibial translation,
      regardless of whether the anterior, central, or posterior fibers were alone
      transected (P = .350). At 90 degrees of knee flexion, whether the posterior
      fibers were cut first, second, or third (order of section), the incremental
      difference in posterior tibial translation this produced was significantly
      different (P = .039). For the fiber regions combined, the third fiber region
      section resulted in a significantly larger incremental translation than did
      either the first or second section with the knee flexed 90 degrees (P = .001).
      After transection of all fiber regions, significantly more total posterior tibial
      translation occurred at 90 degrees versus 20 degrees of flexion (P = .002).
      CONCLUSIONS: This study shows that fiber regions within the PCL have unique
      characteristics and behave differently in response to posterior drawer forces.
      CLINICAL RELEVANCE: This study provides additional information on the complex
      mechanical behavior of the PCL and suggests that some partial tears (ie, those
      involving 1 or 2 fiber regions) may only result in minimal posterior translation
      during drawer testing at 90 degrees .

PMID- 18055919
TI  - Surgical treatment of acute versus chronic complete proximal hamstring ruptures:
      results of a new allograft technique for chronic reconstructions.
AB  - BACKGROUND: Acute surgical repair of proximal hamstring ruptures has been shown
      to result in a high return to preinjury activity level. HYPOTHESIS: Achilles
      allograft reconstruction of chronic complete proximal hamstring ruptures results
      in improved function and strength that approaches that of acute surgical repairs.
      STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Between 2002 and 2005,
      26 patients underwent surgical treatment for complete proximal hamstring
      ruptures. Twenty-one were acute primary repairs. Five chronic ruptures were
      treated with Achilles allograft reconstruction with (n = 2) or without (n = 2)
      interference screw fixation or mobilization and primary repair (n = 1).
      Isokinetic strength testing was conducted postoperatively in 11 acute and 3
      chronic cases, and a functional questionnaire was given at most recent follow-up.
      RESULTS: Subjective results for all patients at a mean follow-up of 20 months
      revealed good leg control in 96%, no pain in 80%, and return to sporting
      activities in 76%. Ninety-six percent of patients said they would have the
      procedure done again. With the isokinetic testing available at most recent follow
      up, there was no significant difference in the mean hamstring strength deficits
      for the acute versus chronic groups tested at 60 deg/s (8% vs 21%, P =.295) and
      180 deg/s (12% vs 2%, P = .294). Overall, there were 3 major adverse events and 5
      patients with superficial wound drainage treated with antibiotics. CONCLUSION:
      Surgical treatment of acute and chronic complete proximal hamstring ruptures can
      result in a high return to full activity. Reconstruction of chronic ruptures with
      Achilles allograft appears to restore function and strength comparable to acute
      repairs.

PMID- 18055920
TI  - A biomechanical comparison of youth baseball pitches: is the curveball
      potentially harmful?
AB  - BACKGROUND: The curveball has been anecdotally considered as a dangerous pitch
      among youth pitchers, especially for their ulnar collateral ligaments. No
      biomechanical studies have been conducted among youth pitchers comparing
      different types of pitches. HYPOTHESIS: The kinetics of the baseball throw varies
      significantly between the fastball, curveball, and change-up for youth pitchers.
      Kinematic and temporal differences are also expected. STUDY DESIGN: Controlled
      laboratory study. METHODS: Twenty-nine youth baseball pitchers (age, 12.5 +/- 1.7
      years) pitched 5 fastballs, 5 curveballs, and 5 change-ups with maximum effort in
      an indoor laboratory setting. Data were collected with a 3-dimensional motion
      analysis system. Kinetic, kinematic, and temporal parameters were compared among
      the 3 pitches. RESULTS: For elbow varus torque, shoulder internal rotation
      torque, elbow proximal force, and shoulder proximal force, the fastball produced
      the greatest values, followed by the curveball and then the change-up. The
      fastball also produced the greatest elbow flexion torque. Shoulder horizontal
      adduction torque and shoulder adduction torque were the least for the change-up.
      Several differences in body segment position, velocity, and timing were also
      found. CONCLUSIONS: In general, elbow and shoulder loads were the greatest in the
      fastball and least in the change-up. Kinematic and temporal differences were also
      found among the 3 pitch types. CLINICAL RELEVANCE: The curveball may not be more
      potentially harmful than the fastball for youth pitchers. This finding is
      consistent with recent epidemiologic research indicating that amount of pitching
      is a stronger risk factor than type of pitches thrown.

PMID- 18055921
TI  - Do capacitively coupled electric fields accelerate tibial stress fracture
      healing? A randomized controlled trial.
AB  - BACKGROUND: Tibial stress fractures increasingly affect athletes and military
      recruits, with few known effective management options. Electrical stimulation
      enhances regular fracture healing, but the effect on stress fractures has not
      been definitively tested. HYPOTHESIS: Capacitively coupled electric field
      stimulation will accelerate tibial stress fracture healing. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 1. METHODS: Twenty men and 24
      women with acute posteromedial tibial stress fractures were referred from local
      clinicians. Subjects were randomly assigned active or placebo capacitively
      coupled electric field stimulation to be applied for 15 hours per day until
      healed, given supplemental calcium, and instructed to rest from provocative
      training. Healing was confirmed when hopping to 10 cm for 30 seconds could be
      achieved without pain. RESULTS: No difference in time to healing was detected
      between treatment and placebo groups. Women in the treatment group healed more
      slowly than did the men (P = .05). Superior treatment compliance was associated
      with reduced time to healing (P = .003). Rest noncompliance was associated with
      increased time to healing (P = .05). CONCLUSION: Whole-group analysis did not
      detect an effect of capacitively coupled electric field stimulation on tibial
      stress fracture healing; however, greater device use and less weightbearing
      loading enhanced the effectiveness of the active device. More severe stress
      fractures healed more quickly with capacitively coupled electric field
      stimulation. CLINICAL RELEVANCE: Although the use of capacitively coupled
      electric field stimulation for tibial stress fracture healing may not be
      efficacious for all, it may be indicated for the more severely injured or elite
      athlete/recruit whose incentive to return to activity may motivate superior
      compliance.

PMID- 18055922
TI  - Age-related rates of decline in performance among elite senior athletes.
AB  - BACKGROUND: Age-related disability and lost independence currently plague one
      third of older Americans. Many causes of disability, lost muscle mass and bone
      mineral density, are modifiable with exercise. Most exemplary of successful aging
      are the Senior Olympians; this group of vital athletes exhibit persistently high
      levels of functional capacity. PURPOSE: This study describes demographic data,
      injury characteristics and the effect of aging on physical performance in senior
      athletes to identify key time points for intervention to address declining
      performance. STUDY DESIGN: Cross-sectional study; Level of evidence, 4. METHODS:
      Senior Olympians (>50 years) participating in the 2001 National Senior Olympic
      Games were surveyed for demographic and health characteristics. Age-related
      changes in physical performance were determined from mean winning performance
      times in track and field events. These were plotted against age and task for men
      and women. Analysis of variance and intergroup significance were analyzed using
      the Tukey procedure. Percentage performance change across events was compared.
      The 2001 National Senior Olympic Games results were compared with American track
      and field record holders. RESULTS: Senior athletes' performance declined (male
      and female) approximately 3.4% per year over 35 years of competition-slowly from
      age 50 to 75 years and dramatically after age 75 years. Men showed no difference
      in decline of sprint and endurance events, whereas the decline in the sprint was
      greater than in endurance for women, especially after the age of 75 years.
      CONCLUSION: Even the healthiest examples of musculoskeletal aging experience
      significant performance declines around age 75 years. This may be a key time
      point for preventive intervention.

PMID- 18055923
TI  - Prediction of psychosis: setting the stage.
AB  - Treating psychotic disorders in their earliest stages has become a key focus for
      research and clinical care. This paper reviews evidence of the capacity to
      identify those at increased risk for psychotic disorder and to intervene in the
      identified, high-risk individuals to ameliorate the course of disorder. Issues
      involved in preventive oriented clinical care are addressed, such as risk/benefit
      considerations, ethical and safety issues and the value of stage-specific
      interventions. Clinical predictors identified in recent research, promising
      intervention trials and proposed clinical practice guidelines are described. An
      approach based on active engagement, support and monitoring, yet with a
      conservative approach to medication use is advocated at present. Potential
      neurobiological processes have been studied and reinforce the sense that this is
      a critical phase for active treatment, and may prove helpful in understanding the
      process of transition across stages of illness. More research is required in
      prediction, neurobiology and treatment.

PMID- 18055924
TI  - Incidence of first-contact psychosis in Sao Paulo, Brazil.
AB  - BACKGROUND: Little is known about the incidence of first-episode psychosis in
      urban centres of low- or middle-income countries. AIMS: To estimate the incidence
      of psychosis in Sao Paulo, a large metropolis of Brazil. METHOD: Prospective
      survey of first-episode psychosis among residents aged 18-64 years resident in a
      defined area of Sao Paulo, over a 30-month period (July 20 2002-December 2004).
      Assessments were carried out with the SCID-I, and diagnoses given according to
      DSM-IV criteria. Population at risk was drawn from the 2000 Census data. RESULTS:
      There were 367 first-episode cases identified (51% women), and almost 40%
      fulfilled criteria for schizophrenia or schizophreniform disorder. The incidence
      rate for any psychosis was 15.8/100 000 person-years at risk (95% CI 14.3-17.6).
      Incidence of non-affective psychoses was higher among younger males. CONCLUSIONS:
      Incidence of psychosis in Sao Paulo was lower than expected for a large
      metropolis.

PMID- 18055925
TI  - Cognitive dysfunction in first-episode psychosis: the processing speed
      hypothesis.
AB  - BACKGROUND: Speed of processing is a cognitive process underlying cognitive
      dysfunction in people with chronic schizophrenia. AIMS: To investigate the
      contribution of speed of processing to the cognitive deficits observed in a
      representative large sample with first-episode schizophrenia. METHOD: People with
      a diagnosis of first-episode schizophrenia-spectrum disorders (n=26) and healthy
      controls (n=28) were compared on several cognitive measures before and after
      controlling for speed of processing. RESULTS: Before controlling for speed of
      processing, patients and controls differed significantly on all cognitive
      measures. All significant differences in cognitive functioning disappeared when
      the result of the Digital Symbol Substitution Test was included as an additional
      covariate. CONCLUSIONS: Speed of information processing may be considered a core
      cognitive deficit in schizophrenia and might be mediating a broader diversity of
      cognitive disturbances.

PMID- 18055926
TI  - Grey matter abnormalities in first-episode schizophrenia and affective psychosis.
AB  - BACKGROUND: Grey matter and other structural brain abnormalities are consistently
      reported in first-onset schizophrenia, but less is known about the extent of
      neuroanatomical changes in first-onset affective psychosis. AIMS: To determine
      which brain abnormalities are specific to (a) schizophrenia and (b) affective
      psychosis. METHOD: We obtained dual-echo (proton density/T2-weighted) magnetic
      resonance images and carried out voxel-based analysis on the images of 73
      patients with first-episode psychosis (schizophrenia n=44, affective psychosis
      n=29) and 58 healthy controls. RESULTS: Both patients with schizophrenia and
      patients with affective psychosis had enlarged lateral and third ventricle
      volumes. Regional cortical grey matter reductions (including bilateral anterior
      cingulate gyrus, left insula and left fusiform gyrus) were evident in affective
      psychosis but not in schizophrenia, although patients with schizophrenia
      displayed decreased hippocampal grey matter and increased striatal grey matter at
      a more liberal statistical threshold. CONCLUSIONS: Both schizophrenia and
      affective psychosis are associated with volumetric abnormalities at the onset of
      frank psychosis, with some of these evident in common brain areas.

PMID- 18055927
TI  - Grey matter abnormalities in Brazilians with first-episode psychosis.
AB  - BACKGROUND: In low- and middle-income countries people with schizophrenia are
      reported to experience better outcomes than those in high-income countries. AIMS:
      To examine structural brain differences in people with first-episode psychosis
      and controls in Brazil. METHOD: Magnetic resonance imaging using voxel-based
      morphometry was performed on 122 people with first-episode psychosis and 94
      controls. RESULTS: There were significant decreases in grey matter in the left
      superior temporal and inferior prefrontal cortices, insula bilaterally and the
      right hippocampal region in first-episode psychosis (P<0.05, corrected for
      multiple comparisons). The subgroup of people with schizophrenia (n=62) exhibited
      a similar pattern of decrease in grey matter relative to controls. CONCLUSIONS:
      Structural abnormalities reported in psychosis in high-income countries are also
      present in first-episode psychosis in Brazil.

PMID- 18055928
TI  - Duration of prodromal phase and severity of volumetric abnormalities in first
      episode psychosis.
AB  - BACKGROUND: First-episode psychosis is typically preceded by a prodrome in which
      there is deterioration in global and social functioning. AIMS: To examine whether
      the duration of the prodromal phase influences grey and white matter volumes at
      the onset of psychosis. METHODS: Eighty-two people were scanned using magnetic
      resonance imaging when they developed a first episode of psychosis. The duration
      of the prodromal phase was estimated from detailed interviews and medical
      records. Voxel-based morphometry was used to assess neuroanatomical
      abnormalities. RESULTS: A long prodromal phase was associated with smaller grey
      matter volumes in the cingulate, frontal and left insular cortex, and with less
      white matter volume bilaterally in the superior longitudinal and uncinate
      fasciculi and the cingulum. CONCLUSIONS: The severity of volumetric abnormalities
      in first-episode psychosis was greater in those with a long prodrome.

PMID- 18055929
TI  - One-year effect of changing duration of untreated psychosis in a single catchment
      area.
AB  - BACKGROUND: There is highly replicated positive correlation between longer
      duration of untreated psychosis and poorer outcome. AIMS: To study the effect of
      early intervention in first psychosis on one-year outcome using an historical
      quasi-experimental design. METHOD: We compare the outcome of two samples of first
      episode psychosis from the same healthcare district at different time periods.
      The historical control sample was assessed during 1993-1994, before the
      establishment of a system for early detection of psychosis. The experimental
      sample is the early detection sample in the Early Treatment and Intervention in
      Psychosis study assessed during 1997-2000. RESULTS: At 1-year follow-up, the
      early detection group was younger, had a smaller fraction of individuals with
      schizophrenia, had less severe negative and general symptoms and had more friends
      in the past year than the historical control group. No differences were found in
      clinical course (remission, relapse, continuously psychotic) or positive
      symptoms, but more patients in the early detection sample were treated as
      outpatients without hospitalisation. CONCLUSIONS: Early detection of
      schizophrenia in one healthcare sector is associated with less severe
      deterioration at 1 year.

PMID- 18055931
TI  - The Lambeth Early Onset Crisis Assessment Team Study: general practitioner
      education and access to an early detection team in first-episode psychosis.
AB  - BACKGROUND: There are few evaluations of strategies to improve rates of early
      detection and treatment of patients with first-episode psychosis. AIMS: To
      evaluate the effectiveness of a general practitioner (GP) education programme and
      an early detection assessment team (the Lambeth Early Onset Crisis Assessment
      Team; LEO CAT) in reducing delays in accessing treatment for first-episode
      psychosis patients. METHOD: 46 clusters of GP practices randomised to GP
      education in early detection with direct access to LEO CAT v. care as usual.
      Primary outcome measures were GP referral rates, duration of untreated psychosis
      (DUP) and delays in receiving treatment. RESULTS: 150 patients with first-episode
      psychosis were recruited; 113 were registered with the study GPs, who referred 54
      (47.7%) directly to mental health services. Significantly more intervention group
      GPs (86.1% v. 65.7%) referred their patients directly to mental health services
      and fewer patients experienced long delays in receiving treatment. However, their
      overall DUP was unaffected. CONCLUSIONS: Educating GPs improves detection and
      referral rates of first-episode psychosis patients. An early detection team
      reduces the long delays in initial assessment and treatment. However, these only
      impact on the later phases of the DUP. Broader measures, such as public health
      education, are needed to reduce the earlier delays in DUP.

PMID- 18055930
TI  - Molecular imaging studies of the striatal dopaminergic system in psychosis and
      predictions for the prodromal phase of psychosis.
AB  - The dopamine hypothesis has been the major pathophysiological theory of psychosis
      in recent decades. Molecular imaging studies have provided in vivo evidence of
      increased dopamine synaptic availability and increased presynaptic dopamine
      synthesis in the striata of people with psychotic illnesses. These studies
      support the predictions of the dopamine hypothesis, but it remains to be
      determined whether dopaminergic abnormalities pre-date or are secondary to the
      development of psychosis. We selectively review the molecular imaging studies of
      the striatal dopaminergic system in psychosis and link this to models of
      psychosis and the functional subdivisions of the striatum to make predictions for
      the dopaminergic system in the prodromal phase of psychosis.

PMID- 18055932
TI  - Suicidal behaviour and mortality in first-episode psychosis: the OPUS trial.
AB  - BACKGROUND: Those with first-episode psychosis are at high-risk of suicide. AIMS:
      To identify predictive factors for suicidal thoughts, plans and attempts, and to
      investigate the rate of suicides and other deaths during the 5 years after first
      diagnosis and initiation of treatment. METHOD: A longitudinal, prospective, 5
      year follow-up study of 547 individuals with first-episode schizophrenia spectrum
      psychosis. Individuals presenting for their first treatment in mental health
      services in two circumscribed urban areas in Denmark were included in a
      randomised controlled trial of integrated v. standard treatment. All participants
      were followed in the Danish Cause of Death Register for 5 years. Suicidal
      behaviour and clinical and social status were assessed using validated interviews
      and rating scales at entry, and at 1- and 2-year follow-ups. RESULTS: Sixteen
      participants died during the follow-up. We found a strong association between
      suicidal thoughts, plans and previous attempts, depressive and psychotic symptoms
      and young age, and with suicidal plans and attempts at 1- and 2-year follow-up.
      CONCLUSIONS: In this first-episode cohort depressive and psychotic symptoms,
      especially hallucinations, predicted suicidal plans and attempts, and persistent
      suicidal behaviour and ideation were associated with high risk of attempted
      suicide.

PMID- 18055933
TI  - Economic evaluation of early intervention services.
AB  - Early intervention services have been introduced in a number of countries, but
      the evidence base to support them is limited. In particular there are very few
      economic evaluations, which are crucial if decision-makers are to have a better
      understanding of how scarce resources can be used appropriately. This paper
      discusses the different approaches used in economic evaluations and shows how
      these differ in the way in which outcomes are measured. The most useful forms of
      evaluation are cost-effectiveness and cost-utility analysis. We describe how the
      results of evaluations can be interpreted using incremental cost-effectiveness
      ratios and acceptability curves. Finally, the paper summarises some key evidence
      to date on early intervention services and economic evaluations currently being
      undertaken.

PMID- 18055934
TI  - Appraisals of Anomalous Experiences Interview (AANEX): a multidimensional measure
      of psychological responses to anomalies associated with psychosis.
AB  - BACKGROUND: Cognitive models of psychosis suggest that whether anomalous
      experiences lead to clinically relevant psychotic symptoms depends on how they
      are appraised, the context in which they occur and the individual's emotional
      response. AIMS: To develop and validate a semi-structured interview (the
      Appraisals of Anomalous Experiences Interview; AANEX) to assess (a) anomalous
      experiences and (b) appraisal, contextual and response variables. METHOD:
      Following initial piloting, construct validity was tested via cross-sectional
      comparison of data from clinical and non-clinical samples with anomalous
      experiences. Interrater reliability was also assessed. RESULTS: Scores from AANEX
      measuring appraisals, responses and social support differentiated the clinical
      and nonclinical groups. Interrater reliability was satisfactory for 65 of the 71
      items. Six items were subsequently amended. CONCLUSIONS: The AANEX is a valid
      multidimensional instrument that provides a detailed assessment of psychotic-like
      experiences and subjective variables relevant to the development of a need for
      clinical care.

PMID- 18055935
TI  - Basic symptoms in early psychotic and depressive disorders.
AB  - BACKGROUND: Depression is a frequent condition in early psychosis. Therefore,
      early detection instruments should distinguish depression from beginning
      psychosis. AIMS: To examine whether basic symptoms, i.e. subtle subjective
      deficits, differ between participants suffering from a potential prodrome
      (n=146), first-episode schizophrenia (n=153) and non-psychotic depression
      (n=115). METHOD: Basic symptoms were assessed with the Schizophrenia Proneness
      Instrument. RESULTS: The prodrome and schizophrenia groups did not differ in
      level of basic symptoms but both had higher levels than the depression group. DSM
      IV depression was frequent in those suffering from a potential prodrome (38%) and
      first-episode schizophrenia (21%). In both groups, participants with and without
      depression did not differ in basic symptoms. In multivariate analyses,
      consideration of current depression generally facilitated correct group
      classification, except for participants suffering from both a potential prodrome
      and depression. CONCLUSIONS: Cognitive basic symptoms distinguished well between
      all three groups. However, identification of persons suffering from a potential
      prodrome might be enhanced by considering current affective status.

PMID- 18055936
TI  - Delusion formation and reasoning biases in those at clinical high risk for
      psychosis.
AB  - BACKGROUND: Cognitive models propose that faulty appraisal of anomalous
      experiences is critical in developing psychosis, particularly delusions. A data
      gathering bias may be fundamental to abnormal appraisal. AIMS: To examine whether
      there is a data gathering bias in people at high risk of developing psychosis.
      METHOD: Individuals with an at-risk mental state (n=35) were compared with a
      matched group of healthy volunteers (n=23). Participants were tested using a
      modified version of the 'beads' reasoning task with different levels of task
      difficulty. RESULTS: When task demands were high, the at-risk group made
      judgements on the basis of less information than the control group (P<0.05).
      Within both groups, jumping to conclusions was directly correlated with the
      severity of abnormal beliefs and intolerance of uncertainty (P<0.05). In the at
      risk group it was also associated with impaired working memory (P<0.05), whereas
      in the control group poor working memory was associated with a more conservative
      response style (P<0.05). CONCLUSIONS: People with an at-risk mental state display
      a jumping to conclusions reasoning style, associated with impaired working memory
      and intolerance of uncertainty. This may underlie a tendency to develop abnormal
      beliefs and a vulnerability to psychosis.

PMID- 18055937
TI  - Relationship between subjective and objective cognitive function in the early and
      late prodrome.
AB  - BACKGROUND: Cognitive disturbances have been demonstrated in individuals with
      potentially prodromal symptoms in objective-neuropsychological as well as
      subjective-symptomatic studies. Yet, the relation between subjective and
      objective deficits and to different prodromal states is unclear. AIMS: To explore
      interactions between subjective and objective cognitive measures in different
      prodromal states. METHOD: In participants with an early (n=33) or late (n=69)
      initial prodromal state, cognitive subjective and objective deficits were
      assessed with the Schizophrenia Proneness Instrument and a comprehensive
      neuropsychological test battery. RESULTS: Participants with an early initial
      prodromal state were less impaired than those with a late initial state.
      Subjective and objective cognitive deficits were unrelated, except time-limited
      neurocognitive speed measures and subjectively reduced stress tolerance,
      especially in participants with an early initial prodromal state. CONCLUSIONS:
      Subjective and objective cognitive deficits are generally unrelated in the
      psychosis prodrome and as such they can add complementary information valuable
      for prediction. However, possible associations between the two levels might be
      better detectable in the less impaired early initial prodromal state.

PMID- 18055938
TI  - Cognitive decline following psychosis onset: data from the PACE clinic.
AB  - BACKGROUND: The origin of cognitive impairments in psychotic disorders is still
      unclear. Although some deficits are apparent prior to the onset of frank illness,
      it is unknown if they progress. AIMS: To investigate whether cognitive function
      declined over the transition to psychosis in a group of ultra-high risk
      individuals. METHOD: Participants consisted of two groups: controls (n=17) and
      individuals at ultra-high risk for development of psychosis (n=16). Seven of the
      latter group later developed psychosis. Neuropsychological testing was conducted
      at baseline and again after at least a 12-month interval. RESULTS: Both the
      Visual Reproduction sub-test of the Wechsler Memory Scale-Revised and Trail
      Making Test B showed a decline over the follow-up period that was specific to the
      group who became psychotic. In addition, both high-risk groups showed a decline
      in digit span performance. No other task showed significant change over time.
      CONCLUSIONS: These preliminary data suggest that as psychosis develops there may
      be a specific decline in visual memory and attentional set-shifting, reflecting
      impairments in efficient organisation of visual stimuli. This may be caused by
      either the illness itself or treatment with antipsychotic medication.

PMID- 18055939
TI  - Impairment of self-monitoring: part of the endophenotypic risk for psychosis.
AB  - BACKGROUND: A disorder of self-monitoring may underlie the positive symptoms of
      psychosis. The cognitive mechanisms associated with these symptoms may also be
      detectable in individuals at risk of psychosis. AIMS: To investigate (a) whether
      patients with psychosis show impaired self-monitoring, (b) to what degree this is
      associated with positive symptoms, and (c) whether this is associated with
      liability to psychotic symptoms. METHOD: The sample included: individuals with a
      lifetime history of non-affective psychosis (n=37), a genetically defined risk
      group (n=41), a psychometrically defined risk group (n=40), and control group
      (n=49). All participants carried out an action-recognition task. RESULTS: Number
      of action-recognition errors was associated with psychosis risk (OR linear trend
      over 3 levels:1.12, 95% CI1.04-1.20) and differential error rate was associated
      with the degree of delusional ideation in a dose-response fashion (OR linear
      trend over 3 levels:1.13, 95% CI1.00-1.26). CONCLUSIONS: Alterations in self
      monitoring are associated with psychosis with evidence of specificity for
      delusional ideation. In the risk state, this is expressed more as failure to
      recognise self-generated actions, whereas in illness failure to recognise alien
      sources come to the fore.

PMID- 18055940
TI  - Virtual reality and paranoid ideations in people with an 'at-risk mental state'
      for psychosis.
AB  - BACKGROUND: Virtual reality provides a means of studying paranoid thinking in
      controlled laboratory conditions. However, this method has not been used with a
      clinical group. AIMS: To establish the feasibility and safety of using virtual
      reality methodology in people with an at-risk mental state and to investigate the
      applicability of a cognitive model of paranoia to this group. METHOD: Twenty-one
      participants with an at-risk mental state were assessed before and after entering
      a virtual reality environment depicting the inside of an underground train.
      RESULTS: Virtual reality did not raise levels of distress at the time of testing
      or cause adverse experiences over the subsequent week. Individuals attributed
      mental states to virtual reality characters including hostile intent. Persecutory
      ideation in virtual reality was predicted by higher levels of trait paranoia,
      anxiety, stress, immersion in virtual reality, perseveration and interpersonal
      sensitivity. CONCLUSIONS: Virtual reality is an acceptable experimental technique
      for use with individuals with at-risk mental states. Paranoia in virtual reality
      was understandable in terms of the cognitive model of persecutory delusions.

PMID- 18055941
TI  - Structural brain abnormalities in individuals with an at-risk mental state who
      later develop psychosis.
AB  - BACKGROUND: Neuroanatomical abnormalities are a well-established feature of
      schizophrenia. However, the timing of their emergence and the extent to which
      they are related to vulnerability to the disorder as opposed to psychotic illness
      itself is unclear. AIMS: To assess regional grey matter volume in the at-risk
      individuals who subsequently developed psychosis. METHOD: Magnetic resonance
      imaging data from at-risk individuals who developed psychosis (n=12) within the
      following 25 months were compared with data from healthy volunteers (n=22) and
      people with first-episode psychosis (n=25). RESULTS: Compared with healthy
      volunteers, individuals who subsequently developed psychosis had smaller grey
      matter volume in the posterior cingulate gyrus, precuneus, and paracentral lobule
      bilaterally and in the left superior parietal lobule, and greater grey matter
      volume in a left parietal/posterior temporal region. Compared with first-episode
      patients, they had relatively greater grey matter volume in the temporal gyrus
      bilaterally and smaller grey matter volume in the right lentiform nucleus.
      CONCLUSIONS: Some of the structural brain abnormalities in individuals with an at
      risk mental state may be related to an increased vulnerability to psychosis,
      while others are associated with the development of a psychotic illness.

PMID- 18055942
TI  - Cognitive and neural processes in non-clinical auditory hallucinations.
AB  - BACKGROUND: The nosological status of auditory hallucinations in non-clinical
      samples is unclear. AIMS: To investigate the functional neural basis of non
      clinical hallucinations. METHOD: After selection from 1206 people, 68
      participants of high, medium and low hallucination proneness completed a task
      designed to elicit verbal hallucinatory phenomena under conditions of stimulus
      degradation. Eight subjects who reported hearing a voice when none was present
      repeated the task during functional imaging. RESULTS: During the signal detection
      task, the high hallucination-prone participants reported a voice to be present
      when it was not (false alarms) significantly more often than the average or low
      participants (P<0.03, d.f.=2). On functional magnetic resonance imaging, patterns
      of activation during these false alarms showed activation in the superior and
      middle temporal cortex (P<0.001). CONCLUSIONS: Auditory hallucinatory experiences
      reported in non-clinical samples appear to be mediated by similar patterns of
      cerebral activation as found during hallucinations in schizophrenia.

PMID- 18055943
TI  - Effects of cognitive therapy on the longitudinal development of psychotic
      experiences in people at high risk of developing psychosis.
AB  - BACKGROUND: There have been recent advances in the identification of people at
      high risk of psychosis and psychological treatments have shown promise for
      prevention. AIMS: To compare the longitudinal course of psychotic experiences and
      emotional dysfunction in high-risk participants receiving cognitive therapy with
      those receiving treatment as usual. METHOD: Data from a recent randomised
      controlled trial of cognitive therapy for people at risk of developing psychosis
      were utilised to examine three different statistical models that were based on
      432 measurements of psychotic experiences and 421 of emotional dysfunction
      (anxiety-depression) contributed by 57 participants across the 13 measurement
      occasions (monthly monitoring for a year). RESULTS: Psychotic experiences and
      emotional dysfunction were correlated and decreased significantly over the course
      of the study, with most improvement in the early months. The reduction in
      positive symptoms, but not emotional dysfunction, was enhanced by allocation to
      cognitive therapy. CONCLUSIONS: Psychotic experiences and emotional dysfunction
      appear to interact in people at risk of developing psychosis. There appears to be
      a specific benefit of cognitive therapy.

PMID- 18055944
TI  - Acute effects of treatment for prodromal symptoms for people putatively in a late
      initial prodromal state of psychosis.
AB  - BACKGROUND: People in a putatively late prodromal state not only have an enhanced
      risk for psychosis but already suffer from mental and functional disturbances.
      AIMS: To evaluate the acute effects of a combined supportive and antipsychotic
      treatment on prodromal symptoms. METHOD: Putatively prodromal individuals were
      randomly assigned to a needs-focused intervention without (n=59) or with
      amisulpride (n=65). Outcome measures at 12-weeks effects were prodromal symptoms,
      global functioning and extrapyramidal side-effects. RESULTS: Amisulpride plus the
      needs-focused intervention produced superior effects on attenuated and full-blown
      psychotic symptoms, basic, depressive and negative symptoms, and global
      functioning. Main side-effects were prolactin associated. CONCLUSIONS:
      Coadministration of amisulpride yielded a marked symptomatic benefit. Effects
      require confirmation by a placebo-controlled study.

PMID- 18055945
TI  - Hypothesis: social defeat is a risk factor for schizophrenia?
AB  - The increased schizophrenia risks for residents of cities with high levels of
      competition and for members of disadvantaged groups (for example migrants from
      low- and middle-income countries, people with low IQ, hearing impairments or a
      history of abuse) suggest that social factors are important for aetiology.
      Dopaminergic dysfunctioning is a key mechanism in pathogenesis. This editorial is
      a selective literature review to delineate a mechanism whereby social factors can
      disturb dopamine function in the brain. Experiments with rodents have shown that
      social defeat leads to dopaminergic hyperactivity and to behavioural
      sensitisation, whereby the animal displays an enhanced behavioural and dopamine
      response to dopamine agonists. Neuroreceptor imaging studies have demonstrated
      the same phenomena in patients with schizophrenia who had never received
      antipsychotics. In humans, the chronic experience of social defeat may lead to
      sensitisation (and/or increased baseline activity) of the mesolimbic dopamine
      system and thereby increase the risk for schizophrenia.

PMID- 18055947
TI  - Psychiatry in pictures. Circumvention (1889) by Charles Altamont Doyle (1832
      1893).

PMID- 18055946
TI  - Aripiprazole in the treatment of the psychosis prodrome: an open-label pilot
      study.
AB  - BACKGROUND: Research studies for the treatment of the putative prodromal phase of
      psychotic disorders have begun to appear. AIMS: To obtain preliminary evidence of
      the short-term efficacy and safety of aripiprazole treatment in people with the
      psychosis prodrome. METHOD: Fifteen participants meeting prodrome criteria (mean
      age 17.1 years, s.d.=5.5) enrolled in an open-label, single-site trial with fixed
      flexible dosing of aripiprazole (5-30 mg/day) for 8 weeks. RESULTS: In the mixed
      effects repeated-measures analysis, improvement from baseline on the Scale of
      Prodromal Symptoms total score was statistically significant by the first week.
      No participant converted to psychosis and 13 completed treatment.
      Neuropsychological measures showed no consistent improvement; mean weight gain
      was 1.2 kg. Akathisia emerged in 8 participants, but the mean Barnes Akathisia
      Scale score fell to baseline levels by the final visit. Adverse events were
      otherwise minimal. CONCLUSIONS: Aripiprazole shows a promising efficacy and
      safety profile for the psychosis prodrome. Placebo-controlled studies are
      indicated.

PMID- 18055948
TI  - Computer-aided psychotherapy: revolution or bubble?
AB  - Research into computer-aided psychotherapy is thriving around the world. Most of
      it concerns computer-aided cognitive-behavioural therapy (CCBT). A recent
      narrative review found 97 computer-aided psychotherapy systems from nine
      countries reported in 175 studies, of which 103 were randomised controlled
      trials. The rapid spread of the mass delivery of psychotherapy through CCBT,
      catalysed in the UK by the National Institute for Health and Clinical
      Excellence's recommendation of two CCBT programmes and the Department of Health's
      CCBT implementation guidance, seems unprecedented. This editorial is a synopsis
      of the current status of CCBT and its future directions.

PMID- 18055949
TI  - Lithium in mood disorders: increasing evidence base, declining use?
AB  - Use of lithium for the treatment of bipolar disorder may be declining even as
      knowledge of the efficacy and side-effects of lithium has increased. Recent meta
      analyses confirm the benefits of maintenance lithium treatment and show that it
      reduces suicide and suicidality. Psychiatrists should continue to utilise this
      efficacious treatment for bipolar disorder.

PMID- 18055950
TI  - Social exclusion and mental health: conceptual and methodological review.
AB  - BACKGROUND: The concept of social exclusion is now widely used in discussions
      about the nature of disadvantage, and there are ongoing initiatives to promote
      social inclusion among those with mental health problems. AIMS: To conduct a
      conceptual and methodological review of social exclusion, focusing initially on
      the origins and definitions of the concept and then on approaches to its
      measurement, both in general and in relation to mental health. METHOD: We used
      two main strategies. First, we utilised expertise within the study team to
      identify major texts and reviews on social exclusion and related topics. Second,
      we searched major bibliographic databases for literature on social exclusion and
      mental health. We adopted a non-quantitative approach to synthesising the
      findings. RESULTS: There is no single accepted definition of social exclusion.
      However, most emphasise lack of participation in social activities as the core
      characteristic. There are a number of approaches to measuring social exclusion,
      including use of indicator lists and dimensions. In the mental health literature,
      social exclusion is poorly defined and measured. CONCLUSIONS: If social exclusion
      is a useful concept for understanding the social experiences of those with mental
      health problems, there is an urgent need for more conceptual and methodological
      work.

PMID- 18055951
TI  - Schizotypal cognitions as a predictor of psychopathology in adolescents with mild
      intellectual impairment.
AB  - BACKGROUND: There is evidence to suggest that among young people with mild
      intellectual disability there are those whose cognitive difficulties may predict
      the subsequent manifestation of a schizophrenic phenotype. It is suggested that
      they may be detectable by simple means. AIMS: To gain adequate cooperation from
      educational services, parents and students so as to recruit a sufficiently large
      sample to test the above hypothesis, and to examine the hypothesis in the light
      of the findings. METHOD: The sample was screened with appropriate instruments,
      and groups hypothesised as being likely or not likely to have the phenotype were
      compared in terms of psychopathology and neuropsychology. RESULTS: Simple
      screening methods detect a sample whose psychopathological and neuropsychological
      profile is consistent with an extended phenotype of schizophrenia. CONCLUSIONS:
      Difficulties experienced by some young people with mild and borderline
      intellectual disability are associated with enhanced liability to schizophrenia.
      Clinical methods can both identify those with this extended phenotype and predict
      those in whom psychosis will occur.

PMID- 18055952
TI  - Mental health of children and adolescents with intellectual disabilities in
      Britain.
AB  - BACKGROUND: Few studies have employed formal diagnostic criteria to determine the
      prevalence of psychiatric disorders in contemporaneous samples of children with
      and without intellectual disabilities. AIMS: To establish the prevalence of
      psychiatric disorders against ICD-10 criteria among children with and without
      intellectual disabilities, the association with social/environmental risk
      factors, and risk attributable to intellectual disability. METHOD: Secondary
      analysis of the 1999 and 2004 Office for National Statistics surveys of the
      mental health of British children and adolescents with (n=641) and without (n=17
      774) intellectual disability. RESULTS: Prevalence of psychiatric disorders was
      36% among children with intellectual disability and 8% among children without
      (OR=6.5). Children with intellectual disabilities accounted for 14% of all
      British children with a diagnosable psychiatric disorder. Increased prevalence
      was particularly marked for autistic-spectrum disorder (OR=33.4), hyperkinesis
      (OR=8.4) and conduct disorders (OR=5.7). Cumulative risk of exposure to social
      disadvantage was associated with increased prevalence. CONCLUSIONS: A significant
      proportion of the elevated risk for psychopathology among children with
      intellectual disability may be due to their increased rate of exposure to
      psychosocial disadvantage.

PMID- 18055953
TI  - Mental health and quality of residential environment.
AB  - BACKGROUND: There is increasing interest in the proposition that residential
      environment can affect mental health. AIMS: To study the degree to which common
      mental disorder clusters according to postcode units and households. To
      investigate whether contextual measures of residential environment quality and
      geographical accessibility are associated with symptoms of common mental
      disorder. METHOD: A total of 1058 individuals aged 16-75 years (response rate
      66%) participated in a cross-sectional survey. The 12-item General Health
      Questionnaire measured symptoms of common mental disorder. RESULTS: Only 2% (95%
      CI 0-6) of the unexplained variation in symptoms existed at postcode unit level,
      whereas 37% (95% CI 27-49) existed at household-level, but the postcode unit
      variation was reduced to zero after adjustments. There was little evidence to
      suggest that residential quality or accessibility were associated with symptoms.
      CONCLUSIONS: There was substantial unexplained variation at the household level
      but we could find no evidence of postcode unit variation and no association with
      residential environmental quality or geographical accessibility. It is likely
      that the psychosocial environment is more important than the physical environment
      in relation to common mental disorder.

PMID- 18055954
TI  - Influence of childhood adversity on health among male UK military personnel.
AB  - BACKGROUND: Exposure to childhood adversity may explain why only a minority of
      combatants exposed to trauma develop psychological problems. AIMS: To examine the
      association between self-reported childhood vulnerability and later health
      outcomes in a large randomly selected male military cohort. METHOD: Data are
      derived from the first stage of a cohort study comparing Iraq veterans and non
      deployed UK military personnel. We describe data collected by questionnaire from
      males in the regular UK armed forces (n=7937). RESULTS: Pre-enlistment
      vulnerability is associated with being single, of lower rank, having low
      educational attainment and serving in the Army. Pre-enlistment vulnerability is
      associated with a variety of negative health outcomes. Two main factors emerge as
      important predictors of ill health: a 'family relationships' factor reflecting
      the home environment and an 'externalising behaviour' factor reflecting
      behavioural disturbance. CONCLUSIONS: Pre-enlistment vulnerability is an
      important individual risk factor for ill health in military men. Awareness of
      such factors is important in understanding post-combat psychiatric disorder.

PMID- 18055955
TI  - Growth trajectory during early life and risk of adult schizophrenia.
AB  - BACKGROUND: Growth abnormalities have been suggested as a precursor to
      schizophrenia, but previous studies have not assessed growth patterns using
      repeated measures. AIMS: To assess the association between early life/later
      childhood growth patterns and risk of schizophrenia. METHODS: Using prospectively
      collected data from a birth cohort (born 1959-1967), measurements of height,
      weight and body mass index (BMI) were analysed to compare growth patterns during
      early life and later childhood between 70 individuals with schizophrenia-spectrum
      disorder (SSD) and 7710 without. RESULTS: For women, growth in the SSD group was
      approximately 1 cm/year slower during early life (P < 0.01); no association was
      observed for men. Later childhood growth was not associated with SSD. Weight
      patterns were not associated with SSD, whereas slower change in BMI was observed
      among the SSD group during later childhood. CONCLUSIONS: The association between
      slower growth in early life and schizophrenia in women suggests that factors
      responsible for regulating growth might be important in the pathogenesis of the
      disorder.

PMID- 18055956
TI  - Cost-effectiveness of selective serotonin reuptake inhibitors and routine
      specialist care with and without cognitive behavioural therapy in adolescents
      with major depression.
AB  - BACKGROUND: Major depression is an important and costly problem among
      adolescents, yet evidence to support the provision of cost-effective treatments
      is lacking. AIMS: To assess the short-term cost-effectiveness of combined
      selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioural therapy
      (CBT) together with clinical care compared with SSRIs and clinical care alone in
      adolescents with major depression. METHOD: Pragmatic randomised controlled trial
      in the UK. Outcomes and costs were assessed at baseline, 12 and 28 weeks.
      RESULTS: The trial comprised 208 adolescents, aged 11-17 years, with major or
      probable major depression who had not responded to a brief initial psychosocial
      intervention. There were no significant differences in outcome between the groups
      with and without CBT. Costs were higher in the group with CBT, although not
      significantly so (P=0.057). Cost-effectiveness analysis and exploration of the
      associated uncertainty suggest there is less than a 30% probability that CBT plus
      SSRIs is more cost-effective than SSRIs alone. CONCLUSIONS: A combination of CBT
      plus SSRIs is not more cost-effective in the short-term than SSRIs alone for
      treating adolescents with major depression in receipt of routine specialist
      clinical care.

PMID- 18055957
TI  - Cost of scaling up mental healthcare in low- and middle-income countries.
AB  - BACKGROUND: No systematic attempt has been made to calculate the costs of scaling
      up mental health services in low- and middle-income countries. AIMS: To estimate
      the expenditures needed to scale up the delivery of an essential mental
      healthcare package over a 10-year period (2006-2015). METHOD: A core package was
      defined, comprising pharmacological and/or psychosocial treatment of
      schizophrenia, bipolar disorder, depression and hazardous alcohol use. Current
      service levels in 12 selected low- and middle-income countries were established
      using the WHO-AIMS assessment tool. Target-level resource needs were derived from
      published need assessments and economic evaluations. RESULTS: The cost per capita
      of providing the core package at target coverage levels (in US dollars) ranged
      from $1.85 to $2.60 $2.60 per year in low-income countries and $3.20 to $6.25 per
      year in lower-middle-income countries, an additional annual investment of $0.18
      0.55 per capita. CONCLUSIONS: Although significant new resources need to be
      invested, the absolute amount is not large when considered at the population
      level and against other health investment strategies.

PMID- 18055958
TI  - Cluster randomised controlled trial of training practices in reattribution for
      medically unexplained symptoms.
AB  - BACKGROUND: Reattribution is frequently taught to general practitioners (GPs) as
      a structured consultation that provides a psychological explanation for medically
      unexplained symptoms. AIMS: To determine if practice-based training of GPs in
      reattribution changes doctor-patient communication, thereby improving outcomes in
      patients with medically unexplained symptoms of 3 months' duration. METHOD:
      Cluster randomised controlled trial in 16 practices, 74 GPs and 141 patients with
      medically unexplained symptoms of 6 hours of reattribution training v. treatment
      as usual. RESULTS: With training, the proportion of consultations mostly
      consistent with reattribution increased (31 v. 2%, P=0.002). Training was
      associated with decreased quality of life (health thermometer difference -0.9,
      95% CI -1.6 to -0.1; P=0.027) with no other effects on patient outcome or health
      contacts. CONCLUSIONS: Practice-based training in reattribution changed doctor
      patient communication without improving outcome of patients with medically
      unexplained symptoms.

PMID- 18055959
TI  - Staff and patient perspectives on unmet need and therapeutic alliance in
      community mental health services.
AB  - BACKGROUND: Therapeutic alliance between clinicians and their patients is
      important in community mental healthcare. It is unclear whether providing
      effective interventions influences therapeutic alliance. AIMS: To assess the
      impact of meeting previously unmet mental health needs on the therapeutic
      alliance between patients and clinicians. METHOD: Secondary analysis of data from
      a longitudinal study assessing 101 patients and paired staff. RESULTS: Patient
      rated unmet need was negatively associated with patient-rated and staff-rated
      therapeutic alliance. Staff-rated unmet need was positively associated with
      patient-rated therapeutic alliance only. Reducing patient-rated unmet need
      increased patient-rated but not staff-rated therapeutic alliance, even when
      controlling for other variables. Reducing staff-rated unmet need increased staff
      rated but not patient-rated therapeutic alliance, but the effect became
      insignificant when controlling for other variables. CONCLUSIONS: Patient-rated
      therapeutic alliance will be maximised by focusing assessment and interventions
      on patient-rated rather than staff-rated unmet need.

PMID- 18055960
TI  - Postcards from the EDge: 24-month outcomes of a randomised controlled trial for
      hospital-treated self-poisoning.
AB  - BACKGROUND: Repetition of self-poisoning is common. AIMS: To report the 24-month
      outcomes of a non-obligatory postcard intervention (plus treatment as usual)
      compared with treatment as usual. METHOD: In a randomised-controlled trial (Zelen
      design) conducted in Newcastle, Australia, eight postcards were sent to
      participants over a 12-month period. The principal outcomes were the proportion
      of participants with one or more repeat episodes of self-poisoning and the number
      of repeat episodes per person. RESULTS: No significant reduction was observed in
      the proportion of people repeating self-poisoning in the intervention group
      (21.2%, 95% CI 17.0-25.3) compared with the control group (22.8%, 95% CI 18.7
      27.0; chi(2)=0.32, d.f.=1, P=0.57); the difference between groups was -1.7% (95%
      CI -7.5 to 4.2). There was a significant reduction in the rate of repetition,
      with an incidence risk ratio of 0.49 (95% CI 0.33-0.73). CONCLUSIONS: A postcard
      intervention maintained the halving of the rate of repetition of hospital-treated
      self-poisoning events over a 2-year period, although it did not significantly
      reduce the proportion of individuals who repeated self-poisoning.

PMID- 18055961
TI  - Efficacy of three screening instruments in the identification of autistic
      spectrum disorders.
AB  - BACKGROUND: Screening instruments for autistic-spectrum disorders have not been
      compared in the same sample. AIMS: To compare the Social Communication
      Questionnaire (SCQ), the Social Responsiveness Scale (SRS) and the Children's
      Communication Checklist (CCC). METHOD: Screen and diagnostic assessments on 119
      children between 9 and 13 years of age with special educational needs with and
      without autistic-spectrum disorders were weighted to estimate screen
      characteristics for a realistic target population. RESULTS: The SCQ performed
      best (area under receiver operating characteristic curve (AUC)=0.90; sensitivity
      0.86; specificity 0.78). The SRS had a lower AUC (0.77) with high sensitivity
      (0.78) and moderate specificity (0.67). The CCC had a high sensitivity but lower
      specificity (AUC=0.79; sensitivity 0.93; specificity 0.46). The AUC of the SRS
      and CCC was lower for children with IQ < 70. Behaviour problems reduced
      specificity for all three instruments. CONCLUSIONS: The SCQ, SRS and CCC showed
      strong to moderate ability to identify autistic-spectrum disorder in this at-risk
      sample of school-age children with special educational needs.

PMID- 18055963
TI  - Hot weather and suicide: a real risk or statistical illusion?

PMID- 18055965
TI  - Avoiding errors about 'margins of error'.

PMID- 18055966
TI  - Austrian firearms: data require cautious approach.

PMID- 18055967
TI  - Austrian firearms: data require cautious approach.

PMID- 18055968
TI  - Cardiovascular risk with antipsychotics: case-control study or survey?

PMID- 18055970
TI  - Psychiatry and faith-based organisations.

PMID- 18055971
TI  - Psychiatry and faith-based organisations.

PMID- 18055974
TI  - The crux of the log rank test. Re: Locasciulli A, Oneto R, Bacigalupo A, Socie G,
      Korthof E, Bekassy A, Schrezenmeier H, Passweg J, Fuhrer M. Outcome of patients
      with acquired aplastic anemia given first line bone marrow transplantation or
      immunosuppressive treatment in the last decade: a report from the European Group
      for Blood and Marrow Transplantation. Haematologica 2007; 92:11-8.

PMID- 18055975
TI  - Severe developmental delay and epilepsy in a Japanese patient with severe
      congenital neutropenia due to HAX1 deficiency.
AB  - HAX1 deficiency has recently been identified as a cause of severe congenital
      neutropenia (SCN), but little is known about the phenotype. We described an SCN
      patient with a homozygous 256C-to-T transition causing an R86X mutation in the
      HAX1 gene. Notably, the patient has been complicated by epilepsy and severe delay
      of motor, cognitive, and intellectual development; each developmental quotient
      was 21-26 at 7 years old. Growth failure and dental development delay were also
      noted. Neurodevelopmental delay in this patient expands the clinical phenotype of
      HAX1 deficiency and suggests an important role of HAX1 on neural development as
      well as myelopoiesis.

PMID- 18055976
TI  - Aggressive systemic mastocytosis with sarcoma-like growth in the skeleton,
      leukemic progression, and partial loss of mast cell differentiation antigens.

PMID- 18055977
TI  - High dose simvastatin does not reverse resistance to vincristine, adriamycin, and
      dexamethasone (VAD) in myeloma.
AB  - In a prospective phase II study, we evaluated the combination of high dose
      simvastatin and VAD chemotherapy in patients with refractory or relapsed multiple
      myeloma. Although treatment was feasible with mild side effects, only 1 of 12
      patients achieved a partial response. According to our predefined criteria this
      was insufficient to continue the study.

PMID- 18055978
TI  - Rituximab for prevention of delayed hemolytic transfusion reaction in sickle cell
      disease.
AB  - Delayed hemolytic transfusion reaction (DHTR), a life-threatening transfusion
      complication in sickle cell disease (SCD), is characterized by a marked
      hemoglobin drop with destruction of both transfused and autologous red blood
      cells (RBCs) and exacerbation of SCD symptoms. One mechanism of RBCs destruction
      is auto-antibody production secondary to transfusion. As rituximab specifically
      targets circulating B cells, we thought that it could be beneficial in preventing
      this immune-mediated transfusion complication. We report the case of a SCD
      patient who previously experienced DHTR with auto-antibodies and who needed a new
      transfusion. DHTR recurrence was successfully prevented by rituximab
      administration prior transfusion, supporting the safe use of rituximab to prevent
      DHTR in SCD patients as a second line approach when other measures failed.

PMID- 18055979
TI  - Somatic mutations of JAK2 exon 12 as a molecular basis of erythrocytosis.

PMID- 18055980
TI  - Rituximab for the treatment of autoimmune cytopenias.

PMID- 18055981
TI  - Health-related quality of life and symptom assessment in clinical research of
      patients with hematologic malignancies: where are we now and where do we go from
      here?

PMID- 18055982
TI  - A randomized controlled 1-year study of daily deferiprone plus twice weekly
      desferrioxamine compared with daily deferiprone monotherapy in patients with
      thalassemia major.
AB  - BACKGROUND AND OBJECTIVES: The aim of this prospective, randomized, 1-year study
      was to compare the efficacy and safety of oral deferiprone (DFP) with those of
      combinations of parenteral desferrioxamine (DFO) with oral DFP. DESIGN AND
      METHODS: A total of 24 patients with thalassemia major were randomized to receive
      one of the following two treatments; DFP given at a daily dose of 75 mg/kg in
      combination with DFO (40-50 mg/kg twice weekly) (n=12) or as single agent (n=12).
      In addition, 12 patients treated with 40-50 mg/kg DFO 5 days weekly were included
      as a reference group without randomization. Changes in liver iron concentration
      (LIC) and serum ferritin (SF) were assessed; total iron excretion (TIE), urinary
      iron excretion (UIE) and iron balance were calculated. Cardiac function and
      toxicity were also examined. DESIGN AND METHODS: SF and LIC were significantly
      reduced after 1 year of combination therapy (p=0.01 and 0.07, respectively). A
      decrease of LIC was observed in all but one patient (87.5%) following the
      combination therapy but in only 42% of patients treated with DFP monotherapy. In
      the DFO reference group, a statistically significant decrease in LIC (p=0.01)
      associated with a substantial decrease in SF (p=0.08) was observed after 1 year.
      The combination regimen resulted in greater TIE compared to DFP monotherapy
      (p=0.08) and was the regimen associated with the highest iron balance compared to
      DFP monotherapy (p=0.04) or standard DFO treatment (p=0.006). INTERPRETATIONS AND
      CONCLUSIONS: The addition of subcutaneous DFO twice weekly to oral DFP 75 mg/kg
      is a highly efficacious and safe chelation therapy providing superior chelation
      activity to that of DFP and likely has an efficacy profile comparable to that of
      standard DFO.

PMID- 18055983
TI  - The frequency of JAK2 exon 12 mutations in idiopathic erythrocytosis patients
      with low serum erythropoietin levels.
AB  - BACKGROUND AND OBJECTIVES: Idiopathic erythrocytosis (IE) is characterized by
      erythrocytosis in the absence of megakaryocytic or granulocytic hyperplasia, and
      is associated with variable serum erythropoietin (Epo) levels. Most patients with
      IE lack the JAK2 V617F mutation that occurs in the majority of polycythemia vera
      patients. Four novel JAK2 mutant alleles have recently been described in patients
      with V617F-negative myeloproliferative disorders presenting with erythrocytosis.
      The aims of this study were to assess the prevalence of JAK2 exon 12 mutations in
      IE patients, and to determine the associated clinicopathological features. DESIGN
      AND METHODS: A cohort of 58 IE patients with low to normal serum Epo levels and
      no known causative mutation were identified from 181 individuals diagnosed with
      IE. Patients' DNA samples were screened for the presence of a JAK2 exon 12
      mutation by allele-specific polymerase chain reaction and sequencing. Bone marrow
      trephines were examined for morphological abnormalities and the erythroid
      activity assessed immunohistochemically. RESULTS: Eight mutation-positive cases
      were identified, including one with a previously undescribed mutant JAK2 exon 12
      allele and another with biallelic involvement. The hematologic features of
      mutation-positive and mutation-negative patients were similar, although Epo
      hypersensitive erythroid progenitors occurred exclusively in patients with an
      exon 12 mutation (p=0.0002; n=15). Patients' bone marrows were moderately
      hypercellular, as the result of erythroid hyperplasia, and several had mild
      megakaryocyte atypia. INTERPRETATION AND CONCLUSIONS: JAK2 exon 12 mutations were
      detected in 27% of patients with low serum Epo levels, all of whom had Epo
      independent erythroid progenitors. Consequently, IE patients presenting with
      either of these features should be tested for the presence of a JAK2 mutation.

PMID- 18055984
TI  - Adhesion molecules and Differentiation Syndrome: phenotypic and functional
      analysis of the effect of ATRA, As2O3, phenylbutyrate, and G-CSF in acute
      promyelocytic leukemia.
AB  - BACKGROUND AND OBJECTIVES: Differentiation Syndrome (DS) is a treatment
      complication which can occur in patients treated with acute promyelocytic
      leukemia (APL) with all transretinoic acid (ATRA) or As(2)O(3), and is
      characterized by enhanced leukocyte transmigration. As(2)O(3), Phenylbutyrate
      (PB) and G-CSF are known to potentiate ATRA effects. Our aim was to analyze the
      changes in expression and function of adhesion molecules induced by ATRA,
      As(2)O(3), G-CSF and PB, and their association. DESIGN AND METHODS: APL blasts
      and NB4 cells were treated with ATRA, As(2)O(3), PB, G-CSF or their association
      and the expression of adhesion molecules was determined by flow cytometry. Cell
      adhesion was evaluated in vitro using Matrigel and for the in vivo analysis, Balb
      c mice were injected with NB4 cells pre-treated with ATRA, As(2)O(3), ATRA+G-CSF
      or ATRA+As(2)O(3). In addition, CD54 and CD18 knock-out mice were injected with
      NB4 cells and concomitantly treated with ATRA. In both models, the MPO activity
      in the lungs was determined 6 hours after the injection of the cells. RESULTS: In
      NB4 and APL blasts, ATRA and As(2)O(3) increased CD54 expression, but no
      synergism was detected. CD11b and CD18 were also up-regulated by ATRA in primary
      cells. PB and G-CSF had no effect, but the latter potentiated ATRA-induced CD18
      up-regulation. These changes were accompanied by increased adhesion to Matrigel
      and to lung microvasculature, and reversed by anti-CD54, anti-CD18 antibodies. In
      CD54 and CD18 knock-out mice the ATRA effect was canceled. INTERPRETATION AND
      CONCLUSIONS: The use of As(2)O(3), PB and G-CSF in association with ATRA should
      not aggravate DS in APL.

PMID- 18055985
TI  - Outcome of adult T-lymphoblastic lymphoma after acute lymphoblastic leukemia-type
      treatment: a GOELAMS trial.
AB  - BACKGROUND AND OBJECTIVES: T-lymphoblastic lymphoma is an infrequent disease
      usually treated as T-acute lymphoblastic leukemia with an induction chemotherapy
      course and sequential reinduction and maintenance chemotherapy. The T-LBL/ALL
      GOELAL02 study evaluated the impact of randomized reinduction chemotherapy
      against intensified conditioning followed by autologous stem cell transplantation
      (ASCT), after an induction regimen of the type used for acute lymphoblastic
      leukemia (ALL). DESIGN AND METHODS: Patients with favorable characteristics were
      randomized to receive chemotherapy or ASCT. Patients with unfavorable
      characteristics (bone marrow involvement and age over 35 years old or
      leukocytosis >30 x 10(9)/L or failure to achieve medullar complete remission [CR]
      after one induction course) received a second induction course and ASCT. RESULTS:
      Among 45 patients, the CR rate was 71% after induction and 87% after a second
      induction course. Within the group of 27 patients with favorable characteristics,
      ten received ASCT and 17 chemotherapy. Ten patients in the group with unfavorable
      characteristics received ASCT. The 7-year overall survival and progression-free
      survival rates were 64 and 65%, respectively. Surprisingly, CR obtained after
      only two induction courses was associated with improved overall survival
      (p=0.04). None of the known prognostic factors significantly affected survival.
      INTERPRETATION AND CONCLUSIONS: Randomized maintenance or high-dose therapy (HDT)
      and ASCT or intensified HDT according to initial presentation gave similar
      overall and relapse-free survival rates. However, HDT allowed sparing of
      mediastinal irradiation and shortened treatment duration.

PMID- 18055986
TI  - The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and
      ATM status in chronic lymphocytic leukemia cells.
AB  - BACKGROUND AND OBJECTIVES: The potential anticancer agent 1-(2-chlorophenyl-N
      methylpropyl)-3-isoquinolinecarboxamide (PK11195), a translocator protein (18KDa)
      (TSPO) ligand, facilitates the induction of cell death by a variety of cytotoxic
      and chemotherapeutic agents. Primary chronic lymphocytic leukemia (CLL) cells
      overexpress TSPO. The aim of this study was to examine the effects of PK11195 on
      CLL cells. Table 1. Characteristics of the patients with chronic lymphocytic
      leukemia. DESIGN AND METHODS: Using cytometric analysis, we studied the cytotoxic
      effects of PK11195 on peripheral B and T lymphocytes from patients with CLL and
      from healthy donors. Western blot and cytometric analyses were used to study the
      mitochondrial effects of PK11195 on CLL cells. Moreover, we analyzed the
      cytotoxic effect of PK11195 in patients' cells with mutated p53 or ATM. RESULTS:
      PK11195 induces apoptosis and had additive effects with chemotherapeutic drugs in
      primary CLL cells. Other TSPO ligands such as RO 5-4864 and FGIN-1-27 also induce
      apoptosis in CLL cells. PK11195 induces mitochondrial depolarization and
      cytochrome c release upstream of caspase activation, and dithiocyana-tostilbene
      2,2- disulfonic acid (DIDS), a voltage-dependent anion channel (VDAC) inhibitor,
      inhibits PK11195-induced apoptosis, demonstrating a direct involvement of
      mitochondria. CLL cells and normal B cells are more sensitive than T cells to
      PK11195-induced apoptosis. Interestingly, PK11195 induced apoptosis in CLL cells
      irrespective of their p53 or ATM status. INTERPRETATION AND CONCLUSIONS: These
      results suggest that PK11195 alone or in combination with chemotherapeutic drugs
      might be a new therapeutic option for the treatment of CLL.

PMID- 18055987
TI  - Thrombin-generating capacity in patients with von Willebrand's disease.
AB  - BACKGROUND AND OBJECTIVES: on Willebrand's disease (VWD) is the most common
      hereditary bleeding disorder. Its severity can be classified on the basis of von
      Willebrand factor (VWF) and factor VIII (FVIII) plasma levels and according to
      the clinical relevance of bleeding episodes. However, patients with very low VWF
      activity may exhibit a mild bleeding tendency. The basis for this heterogeneous
      clinical expression of the deficit is still poorly understood. We investigated
      the relationship between thrombin generation and levels of factor VIII, VWF and
      clinical bleeding tendency. DESIGN AND METHODS: Thrombin generation was measured
      in platelet-rich (PRP) and platelet-poor plasma (PPP) from 53 patients with VWD.
      RESULTS: We observed a statistically significant higher risk of bleeding in
      patients with a low thrombin peak in PRP (OR=14.5; 95% CI=5-41.3). Similar
      results were found in PPP (OR=8.71; 95% CI=3.4-22.3). Two parameters of the
      thrombin generation curve, peak height and thrombin generation speed (slope),
      correlated significantly with VWF:RCo and FVIII levels both in PPP and in PRP.
      Regression analysis showed that thrombin generation was mainly dependent on
      plasma FVIII activity. INTERPRETATION AND CONCLUSIONS: Our results suggest that
      the thrombin generation test, in combination with routine FVIII and VWF
      measurements, could be of interest in the assessment of the individual bleeding
      risk in patients with VWD.

PMID- 18055988
TI  - Laboratory diagnosis and monitoring of desmopressin treatment of von Willebrand's
      disease by flow cytometry.
AB  - BACKGROUND AND OBJECTIVES: von Willebrand's disease (VWD) is a heterogeneous
      bleeding disorder caused by quantitative or qualitative defects in von Willebrand
      factor (VWF). The diagnosis of VWD requires several laboratory tests. The aim of
      our study was to validate a flow cytometric test for the diagnosis of VWD and for
      monitoring the effects of desmopressin therapy. DESIGN AND METHODS: Flow
      cytometric analysis of ristocetin-induced VWF binding to platelets was performed
      in platelet-rich plasma (PRP) samples from patients with VWD and from control
      subjects and in samples of formalin-fixed platelets in the presence of plasma
      from patients or controls. In 12 VWD patients the test was conducted before and 1
      hour after desmopressin infusion. Results were compared with VWF:Ag, VWF:RCo,
      VWF:CB, RIPA, PFA-100 and the skin bleeding time. RESULTS: Ristocetin-induced VWF
      binding to platelets, evaluated by both flow cytometry-based assays, was
      significantly reduced in patients with type1, 2A and 2M VWD as compared with that
      in healthy subjects. Patients with type 2B VWD showed reduced binding of VWF to
      formalin-fixed platelets, but increased binding to autologous platelets in PRP,
      similar to RIPA. VWF binding to platelets assessed by both flow cytometric assays
      correlated significantly with VWF:Ag, VWF:RCo, VWF:CB, RIPA, PFA100 and bleeding
      time. VWF binding to platelets increased after desmopressin infusion.
      INTERPRETATION AND CONCLUSIONS: The measurement of ristocetin-induced binding of
      VWF to platelets by flow cytometry is a sensitive, simple and rapid test for the
      diagnosis of VWD and for the monitoring of the effects of desmopressin therapy.
      The flow cytometric assay performed with autologous platelets is useful in the
      identification of type 2B VWD patients.

PMID- 18055989
TI  - Kinetics of recovery of dendritic cell subsets after reduced-intensity
      conditioning allogeneic stem cell transplantation and clinical outcome.
AB  - BACKGROUND AND OBJECTIVES: Dendritic cells (DC) play a critical role in the
      regulation of alloimmune responses and might influence the outcome of allogeneic
      stem cell transplantation (allo-SCT). We studied the clinical relevance of early
      reconstitution of DC after reduced-intensity conditioning allo-SCT (allo-RIC).
      DESIGN AND METHODS: This study included 79 adult patients undergoing allo-RIC
      from HLA-identical siblings. Peripheral blood samples were drawn from patients at
      1 month (+1m) and 3 months (+3m) after the transplant. DC were identified as
      positive for HLA-DR and negative for CD3, CD19, CD14 and CD56. The expression of
      CD33, CD123 and CD16 was used to identify myeloid DC, plasmacytoid DC and CD16(+)
      DC subpopulations, respectively. RESULTS: Patients whose DC count at +1m was
      lower than the median had a higher probability of treatment-related mortality
      (TRM) (60% vs 12%; p=0.02), poorer overall survival (OS) (15% vs 45%; p=0.002)
      and worse event-free survival (EFS) (20% vs 38%; p=0.03). A multivariate analysis
      confirmed that low DC counts had a detrimental effect on OS (RR 3.2; p=0.007),
      relapse (RR 4.1; p=0.01), and EFS (RR 6; p=0.001). Low CD16(+) DC counts were
      observed to have a detrimental effect on EFS, which was due to both a higher
      incidence of deaths caused by infections (50% vs 0%, p=0.05) and a higher
      incidence of relapse (57% vs 50%; p=0.03). Indeed, the number of CD16(+) DC at +3
      m was the most important prognostic factor for EFS (RR 6; p=0.001).
      Interpretations and Conclusions This study shows the clinical importance of DC
      recovery, especially of the CD16(+) DC subset, in the outcome of patients treated
      with allo-RIC.

PMID- 18055990
TI  - Italian blood donors with anti-HBc and occult hepatitis B virus infection.
AB  - BACKGROUND AND OBJECTIVES: Occult hepatitis B virus (HBV) infection might allow
      the release of viremic units into the blood supply network if blood is tested
      only for hepatitis B surface antigen (HBsAg). The aim of our study was to
      evaluate the actual prevalence, viral load and genotype of occult HBV infections
      among first-time blood donors in north-western Italy and to suggest a way to
      minimize risks of transmission of this infection. DESIGN AND METHODS: We assayed
      6313 consecutive blood donors for antibodies to HBV core antigen (anti-HBc) in
      addition to mandatory screening. HBsAg-negative/anti-HBc-positive donors were
      assayed for antibodies to HBsAg (anti-HBs) and for HBV-DNA using COBAS
      Ampliscreen HBV (Roche) on individual donations. All HBV-DNA-positive samples
      underwent confirmatory testing with additional polymerase chain reaction-based
      assays. RESULTS: The prevalence of anti-HBc positive subjects was 4.85%. Fourteen
      out of 288 blood donors (4.86%) were confirmed to have circulating HBV-DNA at a
      low level (range 8-108 IU/mL). All viremic donors were also anti-HBs-positive.
      INTERPRETATION AND CONCLUSIONS: We estimate that in north-western Italy up to
      2298 units per million donated units from first-time donors may contain HBV-DNA.
      The risk of an HBV-DNA positive unit from an occult carrier being released into
      the blood supply is more than 100 times higher than the estimated residual risk
      related to the window phase of HBV infection in our country. The potential
      infectivity of these units is debated, but their use cannot be considered safe at
      least in immunocompromised patients.

PMID- 18055991
TI  - Differential activation of the death receptor pathway in human target cells
      induced by cytotoxic T lymphocytes showing different kinetics of killing.
AB  - BACKGROUND AND OBJECTIVES: Cytotoxic T lymphocytes (CTL) may use two effector
      mechanisms to kill their target cells: perforin (PFN) and granzyme B (GrB)
      dependent granule-mediated cell death and death receptor-mediated cell death.
      Controversy exists whether, in addition to PFN/GrB-mediated apoptosis, death
      receptor-induced apoptosis contributes to the elimination of human tumor cells by
      CTL. DESIGN AND METHODS: Since the two CTL-mediated effector mechanisms differ in
      time required to eliminate target cells, lysis of target cells was analyzed using
      CTL clones with slow and rapid kinetics of killing derived from a patient with
      chronic myeloid leukemia. To determine the involvement of the death receptor
      pathway, a retroviral construct encoding the antiapoptotic gene FLICE inhibitory
      protein (FLIP) was introduced into these target cells. RESULTS: A CTL clone
      capable of killing 50% of the target cells within 2 hours of incubation primarily
      acted by release of PFN and GrB. In contrast, two CTL clones showing slower
      target cell killing kinetics partially used the death receptor pathway
      (approximately 30% inhibition by FLIP). INTERPRETATION AND CONCLUSIONS: We
      demonstrated that the death receptor pathway contributes to T-cell-mediated cell
      death if not all target cells are destroyed by release of PFN and GrB.

PMID- 18055992
TI  - Predictability of hematopoietic stem cell transplantation rates.
AB  - BACKGROUND AND OBJECTIVES: Hematopoietic stem cell transplantation (HSCT) is a
      complex and expensive procedure. Trends in the use of this procedure have
      appeared erratic in the past. Information on future needs is essential for health
      care administrators. DESIGN AND METHODS: We analyzed the evolution of transplant
      rates, e.g. numbers of transplants per 10 million inhabitants, in Europe from
      1990 to 2004 for all major disease categories and used Gross National Income
      (GNI) per capita, team density (numbers of teams per 10 million inhabitants) and
      team distribution (numbers of teams per 10,000 km2) to measure the impact of
      economic factors in participating countries. Trends were compared by regression
      analyses, and countries were grouped by World Bank definitions into high, middle
      and low income categories. RESULTS: Transplant rates increased over time with
      nearly linear trends, in clear association with GNI per capita (R2=0.72), and
      distinct by World Bank category within a narrow window of variation for both
      autologous HSCT (R2=0.95, 0.98 and 0.94 for high, middle and low income
      categories, respectively) and allogeneic HSCT (R2=0.99, 0.96 and 0.95 for high,
      middle and low income categories, respectively) when breast cancer (autologous)
      and chronic myeloid leukemia (allogeneic) were excluded. Team density (R2=0.72)
      and team distribution (R2=0.51) were also associated with transplant rates.
      INTERPRETATION AND CONCLUSIONS: Transplant rates for HSCT in Europe are highly
      predictable. They are primarily influenced by GNI per capita. The absence of
      saturation and a nearly linear trend indicate that infrastructure lags behind
      medical needs. Isolated changes in single disease entities can easily be
      recognized.

PMID- 18055993
TI  - Antithymocyte globulin and cyclosporine for treatment of 44 children with
      hepatitis associated aplastic anemia.
AB  - We analyzed the outcomes of 44 children with hepatitis associated aplastic anemia
      (HAA) who received immunosuppressive therapy (IST) with antithymocyte globulin
      (ATG) and cyclosporine (CsA). Fourteen (31.8%) patients achieved complete
      response and 17 (38.6%) achieved partial response, for an overall response rate
      of 70.4% after 6 months. Seven non-responders received bone marrow
      transplantation from an HLA-matched unrelated donor and 6 out of 7 are alive. The
      probability of overall survival at 10 years was 88.3+/-4.9%, which supports the
      role of IST with ATG and CsA as treatment of choice for children with HAA without
      an HLA identical sibling donor.

PMID- 18055994
TI  - Rituximab therapy for childhood Evans syndrome.
AB  - The safety and efficacy of rituximab have been retrospectively assessed in 17
      children with Evans syndrome. Patients received 4 or 3 weekly doses of rituximab
      (375 mg/m(2) per dose) associated with prednisone, alone (14 patients) or
      associated with other immunosuppressive drugs. Complete or partial remission of
      at least one cytopenia was achieved in 13 out of the 17 patients (76%), and
      lasted in 11 of them with a mean follow-up of 2.4 years (range 0.5-7 years).
      Steroid therapy was stopped or tapered at 50-100% of the baseline dosage in all
      long-term responders. Moderate side effects and infection occurred only in 4 and
      1 children respectively.

PMID- 18055995
TI  - Activity and safety profile of low-dose rituximab for the treatment of autoimmune
      cytopenias in adults.
AB  - We conducted a retrospective analysis of 11 consecutive patients with various
      autoimmune cytopenias who failed to respond to conventional treatments and
      received a fixed-dose regimen of rituximab (100 mg weekly for 4 consecutive
      weeks). Sustained complete responses were achieved in 4 out of 7 patients with
      idiopathic thrombocytopenic purpura and in 1 patient with autoimmune
      pancytopenia. A partial response was observed in 1 patient with autoimmune
      hemolytic anemia. The immunotherapy had no effect in 1 patient with pure red cell
      aplasia or in 1 patient with autoimmune neutropenia. No infusion-related or
      delayed toxicities attributable to rituximab were experienced by any of the
      patients.

PMID- 18055996
TI  - Atypical BCR-ABL mRNA transcripts in adult acute lymphoblastic leukemia.
AB  - RT-PCR detects chimeric BCR-ABL mRNA in approximately 25% of adult acute
      lymphoblastic leukemia (ALL) cases. Minor breakpoint transcripts (e1a2) are found
      in about 70% of positive cases and major breakpoint transcripts (e13a2, e14a2) in
      about 30% of cases. However, other atypical transcripts are sometimes observed.
      We report experience gained in the GMALL Study Group and identified 8 BCR-ABL
      positive adult ALL cases with such atypical transcripts: 5 with e1a3, 2 with
      e13a3 (b2a3), and 1 with e6a2. This corresponds to a prevalence of 1-2% of all
      BCR-ABL-positive cases. The clinical courses are reported and diagnostic
      proposals are made.

PMID- 18055997
TI  - The risk of venous and arterial thrombosis in hyperhomocysteinemic subjects may
      be a result of elevated factor VIII levels.
AB  - In a large retrospective study of thrombophilic families, we analyzed 405
      relatives of patients, hypothesizing that hyperhomocysteinemia and elevated
      factor VIII levels are closely related. Median factor VIII levels in
      hyperhomocysteinemic relatives were 169 IU/dL, compared with 136 IU/dL in
      normohomocysteinemic relatives (p =0.007), and were more often elevated (>150
      IU/dL; p =0.006). Hyperhomocysteinemia was associated with an increased risk of
      venous and arterial thrombosis; relative risk (RR) 2.6 (CI 1.3-4.8) and 3.7 (CI
      1.5-8.4) respectively. Relatives with elevated FVIII were also at risk; RR 2.3
      (CI 1.4-4.0) for venous thrombosis and 2.3 (CI 1.0-5.1) for arterial thrombosis.
      After excluding all relatives with elevated factor VIII, RR for
      hyperhomocysteinemia and venous thrombosis dropped to 1.3 (CI 0.2-9.8) and no
      relatives had arterial thrombosis. We conclude that it is likely that the
      increased risk of venous and arterial thrombosis in hyperhomocysteinemia is
      mainly related to elevated FVIII levels.

PMID- 18055998
TI  - Human mulipotential mesenchymal/stromal stem cells are derived from a discrete
      subpopulation of STRO-1bright/CD34 /CD45(-)/glycophorin-A-bone marrow cells.
AB  - Magnetic and flow cytometry-based methods were used to characterize clonogenic
      stromal cells in human bone marrow. STRO-1(bright) stromal cells were found to
      lack expression of CD34, CD45 and glycophorin-A markers associated with
      hematopoietic progenitor cells. These studies support the view that these are two
      distinct stem cell compartments in adult bone marrow.

PMID- 18055999
TI  - Endothelial-dependent vasodilation is impaired in children with sickle cell
      disease.
AB  - Impairment of endothelial-dependent vasodilation has been demonstrated in adults
      with sickle cell anemia (SCA). We enrolled 21 SCA children, mean age 10.4+/-3.3
      yrs, and 23 Afro-Caribbean controls. We examined flow-mediated (FMD) and
      nitroglycerine-mediated (GTNMD) dilation of the brachial artery, using
      echotracking techniques, and measured intima-media thickness (IMT) and mechanical
      properties of the common carotid artery. FMD was significantly decreased in SCA
      children vs controls (5.6+/-0.2 vs 8.0+/-0.2%, p=0.008), while IMT, stiffness of
      the common carotid artery, and GTNMD were comparable. In conclusion, endothelial
      dysfunction is present as early as childhood in SCA patients.

PMID- 18056000
TI  - Holotranscobalamin remains unchanged during pregnancy. Longitudinal changes of
      cobalamins and their binding proteins during pregnancy and postpartum.
AB  - We confirm a decrease in cobalamins during pregnancy, and report that the active
      part of cobalamins (holotranscobalamin, holoTC) remains unchanged. The decrease
      in cobalamins is explained by a decreased holohaptocorrin (holoHC), suggesting
      that holoTC rather than cobalamins should be used as a marker of vitamin B12
      deficiency during pregnancy.

PMID- 18056001
TI  - Mutations and haplotype diversity in 70 Portuguese G6PD-deficient individuals: an
      overview on the origin and evolution of mutated alleles.
AB  - G6PD deficiency mutational profile and haplotype diversity using 6 RFLPs
      (FokI/PvuII/BspHI/PstI/BclI/NlaIII) and a (CTT)(n) microsatellite, were
      investigated in 70 G6PD-deficient Portuguese individuals. All but one G6PD A
      (376G/202A) variants (44/45) have a single haplotype (+/+/-/+/-/+/195). G6PD
      Betica(376G/968C) alleles (n=10) have a single RFLP haplotype (+/-/-/+/-/+) and 4
      different (CTT)(n) repeats. Age estimates based on microsatellite variation
      suggest that Betica mutation arose 900 generations ago. G6PD
      SantaMaria(376G/542T) allele was found on haplotype (+/-/-/+/-/+/201) and 10 G6PD
      variants on RFLP haplotypes (-/-/+/+/-/-), (-/-/+/+/-/+) and (-/-/+/+/+/+).

PMID- 18056002
TI  - Missense mutation of the last nucleotide of exon 1 (G->C) of beta globin gene not
      only leads to undetectable mutant peptide and transcript but also interferes with
      the expression of wild allele.
AB  - Hemoglobin Monroe (beta globin G->C, codon 30) is a missense mutation. We could
      not detect either the mutant peptide or transcript in reticulocyte-enriched
      preparation and in expanded erythroid progenitor cells. By quantitative gene
      expression assay beta globin mRNA was found to be reduced by more than 70% in all
      heterozygous subjects with different haplotypes. We conclude that this mutation
      also interferes with expression of wild type allele.

PMID- 18056003
TI  - JAK2 exon 12 mutations in polycythemia vera or idiopathic erythrocytosis.
AB  - JAK2 exon 12 mutations were detected in 4 out of 20 polycythemia vera and
      idiopathic erythrocytosis V617F-negative patients and were only present in the
      myeloid lineage. Initial hematologic data of these patients differ from those of
      V617F-positive patients, but there is no difference in thrombotic development and
      myelofibrotic transformation.

PMID- 18056004
TI  - A randomized comparison of immediate versus delayed application of G-CSF in
      induction therapy for patients with acute myeloid leukemia unfit for intensive
      chemotherapy.
AB  - We randomized 66 elderly patients with AML unfit for conventional chemotherapy to
      receive GCSF from d6 or from d12 after induction-chemotherapy with
      cytarabine/idarubicin. There was no difference in duration of neutropenia (17
      days vs. 19 days, p=0.67) or rate of complications. Delayed treatment can reduce
      the administration of G-CSF without adverse consequences.

PMID- 18056006
TI  - Imatinib mesylate in combination with chemotherapy in four children with de novo
      and advanced stage Philadelphia chromosome-positive acute lymphoblastic leukemia.
AB  - The role of imatinib in childhood Philadelphia chromosome-positive (Ph(+)) acute
      lymphoblastic leukemia (ALL) has not been established. We treated four children
      with imatinib in combination with conventional chemotherapy (CT) before stem cell
      transplantation (SCT). Response evaluation consisted of fluorocytometric analysis
      of minimal residual disease (MRD) and standard qualitative RT-PCR follow-up.

PMID- 18056005
TI  - Imatinib mesylate in the treatment of newly diagnosed or refractory/resistant c
      KIT positive acute myeloid leukemia. Results of an Italian Multicentric Phase II
      Study.
AB  - We evaluated safety and efficacy of imatinib (600 mg) in 36 c-KIT+ acute myeloid
      leukemia patients not amenable to receive conventional chemotherapy. No patient
      achieved complete remission. One patient obtained a hematologic improvement
      (platelet increase with transfusion independence). Median overall survival was 3
      months (0.5-44+). Non-hematologic toxicity was overall mild.

PMID- 18056007
TI  - Evaluation of genetic markers linked to hemophilia A locus: an Indian experience.
AB  - Hemophilia A is an X-linked recessive bleeding disorder caused by defects in
      factor VIII gene (F8). Our study examines variations of single nucleotide
      polymorphism (SNP) in F8 in the Indian population and establishes the utility of
      a combination of SNP and microsatellite markers for the successful identification
      of carriers in the affected families.

PMID- 18056008
TI  - Successful unrelated cord blood transplantation for a patient with CD40 ligand
      deficiency.
AB  - We report a CD40 ligand deficiency (CD40LD) patient who was successfully treated
      with unrelated cord blood transplantation (URCBT). Conditioning regimen was
      busulfan and cyclophosphamide. The clinical course was uneventful and durable
      engraftment was achieved. This successful case encourages the use of URCB as an
      alternative donor source for CD40LD patients.

PMID- 18056010
TI  - Evaluation of foot pain in the standing horse by magnetic resonance imaging.
AB  - The records of 41 horses with previously undiagnosed foot pain that had been
      examined by standing magnetic resonance imaging were reviewed and follow-up
      information was obtained from their owners two years after the examination. A
      range of soft tissue and osseous abnormalities were identified, with multiple
      lesions frequently occurring. Deep digital flexor tendonitis was recorded in 12
      of the horses, and distension of the distal interphalangeal joint was identified
      in 15, but it was not always associated with lameness; in contrast, distension of
      the navicular bursa was always associated with lameness in the seven affected
      horses. Navicular bone lesions were identified in 13 of the horses, often in the
      absence of radiographic changes. Follow-up information was obtained for 35 of the
      horses, 27 of which were alive; of these, 16 had returned to their previous level
      of performance. Of the five horses with navicular bursal changes, four had been
      euthanased owing to lameness and the other had returned to work at a reduced
      level.

PMID- 18056011
TI  - Radiographic assessment of the progression of osteoarthrosis in the contralateral
      stifle joint of dogs with a ruptured cranial cruciate ligament.
AB  - The formation and progression of osteoarthrosis in the unaffected contralateral
      stifle joints of 14 dogs with a unilateral cranial cruciate ligament rupture were
      monitored radiographically in terms of a global score and the scores for 10
      parameters specific for the stifle joint. The dogs were examined initially and
      six and 12 months later by three observers, and the variability between the
      observers' scores was also assessed. The score for osteophytes at the tibial
      attachment site of the ligament was the most reliable parameter, and that for the
      increase in femoropatellar joint space was the least reliable. In the
      contralateral stifle joints there were significant increases after six and 12
      months in osteophyte formation caudal to the tibial plateau, and in subchondral
      sclerosis of the tibial plateau and of the long digital extensor muscle groove.
      These three parameters progressed more regularly during the disease process than
      the other parameters. The global osteoarthrosis score of the contralateral stifle
      joint was an important risk factor for sustaining a rupture of the cranial
      cruciate ligament in that joint during the next six months.

PMID- 18056009
TI  - Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional
      recovery and axonal growth after lateral funiculus injury in the adult rat.
AB  - OBJECTIVE: The myelin protein Nogo inhibits axon regeneration by binding to its
      receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40)
      promotes growth of injured corticospinal axons and recovery of motor function
      following a dorsal hemisection. The authors used a similar design to examine
      recovery and repair after a lesion that interrupts the rubrospinal tract (RST).
      METHODS: Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was
      delivered to the cervical spinal cord for 4 weeks. Outcome measures included
      motor and sensory tests and immunohistochemistry. RESULTS: Gait analysis showed
      recovery in the NEP1-40-treated group compared to operated controls, and a test
      of forelimb usage also showed a beneficial effect. The density of labeled RST
      axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus
      rostral to the lesion and contralaterally in both gray and white matter. Thus,
      rubrospinal axons exhibited diminished dieback and/or growth up to the lesion
      site. This was accompanied by greater density of 5HT and calcitonin gene-related
      peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group.
      CONCLUSIONS: NgR blockade after RST injury is associated with axonal growth
      and/or diminished dieback of severed RST axons up to but not into or beyond the
      lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to
      and into the lesion/matrix site. NgR blockade also supported partial recovery of
      function. The authors' results indicate that severed rubrospinal axons respond to
      NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal
      root axons.

PMID- 18056012
TI  - Use of ultrasonography to detect calcifications in cattle and sheep fed Trisetum
      flavescens silage.
AB  - Twelve cows (mean age 6.4 years) and eight sheep (mean age 0.8 years) were fed
      silage containing 70 to 90 per cent vitamin D3-effective Trisetum flavescens for
      a period of 14 weeks. At the beginning and the end of this period, the animals
      were examined and their kidneys, abdominal aortas and heart valves were examined
      by ultrasonography; the animals were then slaughtered and these organs were
      examined histologically, and the specificity and sensitivity of the
      ultrasonography were calculated. After the feeding period, all the cows had a
      decreased body temperature and all but one had raised hair, movement disorders
      and difficulty in rising and lying down. Ultrasonography of the abdominal aorta
      had a specificity of 90 per cent and a sensitivity of 75 per cent, and
      ultrasonography of the heart valves had a specificity of 100 per cent and a
      sensitivity of 50 per cent. In the sheep, cardiac arrythmia was the only
      pathological finding at the end of the feeding period, and the ultrasonographic
      examination of the kidneys had a specificity and sensitivity of 100 per cent.

PMID- 18056013
TI  - Risk of vomiting and diarrhoea in dogs.

PMID- 18056014
TI  - Ultrasonographic diagnosis of reticular diaphragmatic hernias in buffaloes.

PMID- 18056015
TI  - Segmental atresia of the uterus associated with hydrometra in a ferret.

PMID- 18056016
TI  - Responsibilities of animal health.

PMID- 18056017
TI  - Time to recognise experienced unqualified nurses?

PMID- 18056018
TI  - Anthelmintic use in goats.

PMID- 18056019
TI  - Favourable response to electric collar aversion training.

PMID- 18056020
TI  - Lethal bluetongue virus infection in an alpaca.

PMID- 18056021
TI  - TRH stimulation when basal TSH is within the normal range: is there "sub
      biochemical" hypothyroidism?

PMID- 18056022
TI  - Associated economic impact of skatepark-related injuries in Southern California.
AB  - OBJECTIVE: To correlate the types of skatepark-related injuries with medical
      expenses and the monetary effects of time missed from work or school. DESIGN:
      Prospective case series and survey with repeat measures over 1 year. SETTING:
      Southern California Level I Trauma Center and Emergency Department. PARTICIPANTS:
      Subjects age 7 years or older who sustained an injury at a local skatepark and
      treated in the emergency department were included in the study. METHODS: A
      skatepark-related injury survey was conducted at the time of the subject's
      emergency department evaluation. Thereafter, subjects were contacted by telephone
      at 1 week and 1, 3, 6, 9 and 12 months post-injury to assess the extent of
      ongoing follow-up medical care, time lost from work and school for both the
      subject and parents, and the degree of self-reported disability. The costs of
      injury were estimated using accepted econometric methods. The cost of medical
      care and lost household productivity were estimated using data specific to the
      nature of the injury and the body part injured. RESULTS: Skatepark-related
      injuries resulted in a mean loss of 1.1 school days and 5.5 work days to the
      subject and family. The mean total injury costs were $3,167, of which 64% were
      medical costs and 28% were wages lost by the subject and family. Costs were much
      greater for subjects aged 26 years and older than for younger subjects and for
      those with more severe injuries than for less severe injuries. CONCLUSION:
      Skatepark injuries resulted in substantial medical costs and lost wages. Injured
      skatepark users 26 years and older and those with more severe injuries had the
      highest cost.

PMID- 18056023
TI  - Fixation of winged scapula in facioscapulohumeral muscular dystrophy.
AB  - OBJECTIVE: To verify if stabilizing the scapulothoracic joint without arthrodesis
      could lead to functional improvement of shoulder range of motion and clinical
      improvement of winged scapula, we incorporated four additional patients into our
      previous analysis to determine if the results obtained were long lasting, and to
      compare this fixation with the other techniques described in the literature,
      balancing the benefits with the complications. DESIGN: A retrospective study.
      PARTICIPANTS: Thirteen patients with bilateral winged scapula affected by
      facioscapulohumeral muscular dystrophy. Nine of these patients had been analyzed
      in our previous study. METHODS: Patients were operated on by bilateral fixing of
      the scapula to the rib cage using metal wires without arthrodesis (scapulopexy).
      RESULTS: All patients experienced improvement in active range of motion of the
      shoulder and all of them had clinical improvement with complete resolution of the
      winged scapula. In all twenty-six surgical interventions of scapulopexy, a stable
      and long-lasting fixation of the scapula to the rib cage was achieved. The
      complications strictly associated to the surgical technique encountered were one
      pneumothorax, which was resolved spontaneously, and one wire breakage without
      trauma. Average follow-up was 10 years (range, 3 to 18 years). CONCLUSION: The
      scapulopexy used in this extended series of patients consisted of repositioning
      the scapula and fixing it to four ribs by using metal wires without performing
      arthrodesis. This technique has a low rate of complications, is reproducible,
      safe and effective, resulting in clinical and functional improvement.

PMID- 18056024
TI  - Testicular microlithiasis: another starry sky appearance.

PMID- 18056025
TI  - Noninvasive cardiac imaging with computed tomography.
AB  - Despite major improvements in the treatment of heart disease, it remains a major
      source of morbidity and mortality on a global scale. Currently, invasive coronary
      angiography remains the gold standard for identification of obstructive coronary
      artery disease. However, recent advances in computerized tomographic (CT)
      techniques of the heart allow for accurate, noninvasive characterization of
      atherosclerotic coronary disease and other cardiac abnormalities. The calculation
      of coronary artery calcium scores with electron beam CT has largely been
      supplanted by high-resolution CT angiography using multislice detectors (MSCT)
      which can provide detailed multidimensional visualization of cardiac structures.
      Although evaluation of obstructive coronary disease is the primary use of MSCT,
      its use in identifying congenital defects, planning thoracic procedures and
      characterizing cardiac function continues to grow. Accordingly, appropriate
      incorporation of MSCT/CT angiography into clinical practice continues to be
      defined. Several limitations to MSCT remain which reduce its accuracy, such as in
      patients with arrhythmia and in patients with either coronary stents or heavily
      calcified coronaries. Despite its current limitations, MSCT remains a rapidly
      advancing field and an increasingly valuable tool for the noninvasive evaluation
      of cardiac pathology.

PMID- 18056026
TI  - Cocaine-induced acute myocardial infarction.
AB  - Acute myocardial infarction may occur following cocaine use. Cocaine-induced
      infarction is particularly common in younger patients aged 18 to 45 years old.
      Patients may or may not have angiographic evidence of coronary artery disease at
      the time of their acute event. Previous studies have shown that coronary artery
      spasm occurs with cocaine use, and perhaps platelet activation, both contributing
      to a process that may culminate in coronary artery occlusion. Primary coronary
      intervention should be the preferred revascularization modality by an experienced
      team. Thrombolytic therapy needs to be instituted if this intervention is
      unavailable. Beta blockers should be utilized with caution since they may
      increase coronary spasm or cause a paradoxical rise in blood pressure. They
      should be avoided in the early hours of the infarction, but be instituted prior
      to patient discharge. Interruption of cocaine abuse is the cornerstone of
      secondary prevention in cocaine-related myocardial infarction.

PMID- 18056027
TI  - The contribution of luteinizing hormone to Alzheimer disease pathogenesis.
AB  - Several hypotheses have been proposed that attempt to explain the pathogenesis of
      Alzheimer Disease (AD) including theories involving senile plaque and
      neurofibrillary tangle formation, increased oxidative stress, and cell cycle
      abnormalities, since evidence for each of these pathological phenomena have been
      well documented in AD. Recent epidemiological and experimental data also support
      a role for the gonadotropin luteinizing hormone in AD. Paralleling the female
      predominance for developing AD, luteinizing hormone levels are significantly
      higher in females as compared to males, and furthermore, luteinizing hormone
      levels are higher still in individuals who succumb to AD. Luteinizing hormone,
      which is capable of modulating cognitive behavior, is not only present in the
      brain, but also has the highest receptor levels in the hippocampus, a key
      processor of cognition that is severely deteriorated in AD. Furthermore, we
      recently examined cognitive performance in a well-characterized transgenic mouse
      that over-expresses luteinizing hormone and found that these animals show
      decreased cognitive performance when compared to controls. We have also found
      that abolishing luteinizing hormone in amyloid-beta protein precursor transgenic
      mice (Tg2576) using a potent gonadotropin-lowering gonadotropin-releasing hormone
      agonist, leuprolide acetate, resulted in improved hippocampally-related cognitive
      performance and decreased amyloid-beta deposition. These findings, together with
      data indicating that luteinizing hormone modulates amyloid-beta protein precursor
      processing in vivo and in vitro, suggest that luteinizing hormone may contribute
      to AD pathology through an amyloid-dependent mechanism. These promising findings
      support the importance of luteinizing hormone in AD and bring to the forefront an
      alternative, and much needed, therapeutic avenue for the treatment of this
      insidious disease.

PMID- 18056030
TI  - Retraction - Sudbo J. Novel management of oral cancer: a paradigm of predictive
      oncology. Clin Med Res 2004;2:233-242.

PMID- 18056031
TI  - The second conference on skeletal medicine and biology: special features.

PMID- 18056028
TI  - Celiac disease and autoimmune thyroid disease.
AB  - Celiac disease (CD) or gluten sensitive enteropathy is relatively common in
      western populations with prevalence around 1%. With the recent availability of
      sensitive and specific serological testing, many patients who are either
      asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD
      have modest increases in risks of malignancy and mortality compared to controls.
      The mortality among CD patients who comply poorly with a gluten-free diet is
      greater than in compliant patients. The pattern of presentation of CD has altered
      over the past three decades. Many cases are now detected in adulthood during
      investigation of problems as diverse as anemia, osteoporosis, autoimmune
      disorders, unexplained neurological syndromes, infertility and chronic
      hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased
      prevalence of CD has been found in patients with autoimmune thyroid disease, type
      1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease.
      Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes
      mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary
      biliary cirrhosis in prospective studies. Conversely, there is also an increased
      prevalence of immune based disorders among patients with CD. The pathogenesis of
      co-existent autoimmune thyroid disease and CD is not known, but these conditions
      share similar HLA haplotypes and are associated with the gene encoding cytotoxic
      T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as
      those with autoimmune diseases, is a reasonable strategy given the increased
      prevalence. Treatment of CD with a gluten-free diet should reduce the recognized
      complications of this disease and provide benefits in both general health and
      perhaps life expectancy. It also improves glycemic control in patients with type
      1 diabetes mellitus and enhances the absorption of medications for associated
      hypothyroidism and osteoporosis. It probably does not change the natural history
      of associated autoimmune disorders.

PMID- 18056029
TI  - Sex differences in hepatic gluconeogenic capacity after chronic alcohol
      consumption.
AB  - Alcohol-induced hypoglycemia has traditionally been attributed to the amount of
      ethanol consumed rather than any inherent decline in glucose output capacity by
      the gluconeogenic organs and/or an increase in skeletal muscle glucose uptake.
      Further, while the potential for sex differences that might impact glucose
      homeostasis following chronic alcohol consumption has been recognized, direct
      evidence has been noticeably absent. This paper will provide a brief review of
      past and present reports of the potential for sex differences in glucose
      homeostasis following chronic ethanol consumption. This paper will also provide
      direct evidence from our laboratory demonstrating sex differences from chronic
      alcohol consumption resulting in a decrement in glucose appearance and more
      importantly, a specific decline in hepatic gluconeogenic (HGN) capacity in the
      absence and presence of ethanol. All our studies involved 8 weeks of chronic
      alcohol consumption in male and female Wistar rats, as well as a 24 to 48 hour
      fast to deplete hepatic glycogen stores. Under the conditions of chronic alcohol
      consumption and an acute dose of ethanol, we provide in vivo evidence of an early
      decline in whole body glucose appearance in females fed an ethanol diet compared
      to controls. While the decline was also observed in males fed the alcohol diet,
      it occurred much later compared to ethanol fed females. The site for the decline
      in whole body glucose production (i.e., either the kidneys or the liver) was
      beyond the scope of our prior in vivo study. In a follow-up study using the in
      situ perfused liver preparation, we provide additional evidence for a specific
      reduction in HGN capacity from lactate in ethanol fed females compared to ethanol
      fed males in the absence of alcohol in the perfusion medium. Finally, employing
      the isolated hepatocyte technique, we report decrements in HGN from lactate in
      ethanol fed females compared to ethanol fed males in the presence of ethanol in
      the incubation medium. The mechanism for the specific decline in HGN within the
      liver of ethanol fed females remains to be determined. To the extent that our
      observations in animals can be extrapolated to humans, we conclude that alcoholic
      women are more susceptible to ethanol-induced hypoglycemia compared to alcoholic
      men.

PMID- 18056032
TI  - Historical reflections and the future.
AB  - This meeting has excitingly described the modern status of skeletal biology. Many
      advances are described in detail but it may be of value to describe the original
      discovery of two iconic osteoclast regulators, calcitonin and PTH, whose
      development in the 1960s initiated the revolution in the field.

PMID- 18056033
TI  - Oxygen sensing and osteogenesis.
AB  - Osteogenesis and angiogenesis are tightly coupled during bone formation and
      repair. Blood vessels not only carry oxygen and nutrients to the developing bone,
      but also play an active role in bone formation and remodeling by mediating the
      interaction between osteoblasts, osteocytes, osteoclasts, and vascular cells at a
      variety of levels. Tissue hypoxia is believed to be a major stimulus for
      angiogenesis by activating hypoxia-inducible factor alpha (HIFalpha) pathway,
      which is a central regulator of hypoxia adaptation in vertebrates. HIFalpha
      remains inactive under normoxic conditions through pVHL-mediated
      polyubiquitination and proteasomal degradation. Activation of the HIFalpha
      pathway by hypoxia triggers hypoxia-responsive gene expression, such as vascular
      endothelial growth factor (Vegf), which plays a critical role in angiogenesis,
      endochondral bone formation, and bone repair following fracture. Recent work from
      our laboratory has shown that osteoblasts use the HIFalpha pathway to sense
      reduced oxygen tension and transmit signals that impinge on angiogenic and
      osteogenic gene programs during bone formation. Using a genetic approach, we have
      demonstrated that overexpression of HIFalpha in mouse osteoblasts through
      disruption of Vhl results in profound increases in angiogenesis and osteogenesis,
      which appear to be mediated by cell nonautonomous mechanisms involving VEGF.
      These studies suggest that VEGF exerts many of its actions on bone indirectly by
      stimulation of angiogenesis. Whether or to what extent this angiogenic factor
      functions independent of endothelial cells remains to be determined.

PMID- 18056034
TI  - Perspective on the osteoclast: an angiogenic cell?
AB  - There have been reports recently that the osteoclast stimulates angiogenesis in
      vitro. We review the evidence suggesting that the osteoclast directly stimulates
      angiogenesis, and discuss the feasibility of the hypothesis that the osteoclast
      can be a proangiogenic cell. Reasons supporting the feasibility of this
      hypothesis include proangiogenic factors produced by osteoclasts, the angiogenic
      effects of macrophages, the antiangiogenic effects of nitrogen containing
      bisphosphonates, and the physical proximity of osteoclasts to endothelial cells.

PMID- 18056035
TI  - Fetal growth plate: a developmental model of cellular adaptation to hypoxia.
AB  - Fetal growth plate chondrocyte is a unique mesenchymal tissue, as it is avascular
      and hypoxic. Yet, chondrocytes not only survive in this environment, but also
      undergo all cellular processes (proliferation, growth arrest, differentiation,
      etc.) required for normal endochondral bone development. A crucial mediator of
      the adaptive response of cells to hypoxia is a transcription factor named hypoxia
      inducible factor 1alpha (Hif-1alpha). One target of Hif-1alpha transcriptional
      activation is the angiogenic factor vascular endothelial growth factor (VEGF),
      whereas Hif-1alpha accumulation is controlled by the von Hippel-Lindau (VHL)
      tumor suppressor, an E3-ubiquitin ligase that induces its degradation by the
      proteasome. We, and others, demonstrated that each component of this pathway is a
      critical regulator of endochondral bone development. In particular, we previously
      established that Hif-1alpha is a survival factor for hypoxic chondrocytes, and
      that it also negatively regulates cell proliferation. Interestingly, we also
      showed that hypoxia increases extracellular matrix accumulation in a Hif-1alpha
      dependent fashion. This suggested that Hif-1alpha could be critically important
      not only for cell survival and proliferation but also for cell differentiation.
      We recently demonstrated that Hif-1alpha is indeed a differentiation factor since
      it is required in mesenchymal cells both for early chondrogenesis, and for joint
      development.

PMID- 18056036
TI  - Vascular Bmp Msx2 Wnt signaling and oxidative stress in arterial calcification.
AB  - Studies of fracture repair have revealed that paracrine endothelial-mesenchymal
      interactions direct bone formation that restores osseous integrity. Angiogenic
      growth factors and specific members of the bone morphogenetic protein (BMP)
      family mediate these interactions. Recently, these same signals have been shown
      to be critical in the vascular pathobiology of hypertension, diabetes, and
      atherosclerosis. In the arterial vasculature, mechanical and inflammatory redox
      signals, characteristic of hypertension and diabetes have emerged as a
      secretagogues for BMP production-with downstream activation of endothelial NADPH
      oxidases (Nox). Preliminary data now indicate that the paracrine signals provided
      by BMP and reactive oxygen species augment aortic myofibroblast Msx2-Wnt
      signaling and matrix turnover. The net mural response to these stimuli promotes
      osteogenic differentiation of calcifying vascular cells, moreover, oxidation of
      vascular LDL cholesterol generates oxysterols that trigger Runx2 activity via
      hedgehog pathways. Thus, BMP, Wnt, and hedgehog gene expression programs
      osteogenic pathways highly familiar to the bone biologist-are elaborated in the
      arterial vasculature via redox-regulated mechanisms. In the brief review, we
      recount mounting evidence that points to oxidative stress as a major contributor
      to the pathobiology of diabetic arterial calcification.

PMID- 18056038
TI  - Stem cell therapy in bone repair and regeneration.
AB  - Stem cells of various origins, particularly endothelial progenitor cells (EPCs),
      have potential to enhance bone repair and regeneration. EPCs are resident in the
      bone marrow and home to ischemic sites to initiate vasculogenesis. Although it
      was previously believed that only local endothelial cells arrive at ischemic
      sites, new evidence suggests that EPCs are recruited from the periphery. This
      finding has a considerable array of therapeutic implications. For example,
      administered EPCs can localize to sites of osteogenesis where they increase blood
      vessel formation; this may be useful in enhancing fracture repair.

PMID- 18056037
TI  - Hypoxia-mediated mitochondrial stress in RAW264.7 cells induces osteoclast-like
      TRAP-positive cells.
AB  - Previously we showed that mitochondrial dysfunction induced by mitochondrial DNA
      depletion or treatment with electron transport chain inhibitors triggers a stress
      signaling involving activation of calcineurin and Ca2+-responsive factors. In
      this study we show that exposure of RAW 264.7 cells to hypoxia, causing increased
      reactive oxygen species (ROS) production and disruption of mitochondrial
      transmembrane potential, also induced a similar stress signaling. Hypoxia caused
      increased [Ca2+]c, activation of cytosolic calcineurin and induced expression of
      Ryanodine Receptor 2 (RyR2) gene. Prolonged hypoxia (5% O2 for 5-6 days) also
      induced the expression of calcitonin receptor at high levels, and those of
      cathepsin K, and tartarate-resistant alkaline phosphatase (TRAP) at low-moderate
      levels in macrophage cells. Addition of RANKL had an additive effect suggesting
      different mechanisms of activation. Consistent with this possibility, prolonged
      hypoxia induced the formation of TRAP-positive osteoclast-like cells suggesting
      the occurrence of an autocrine mechanism for osteoclastogenesis.

PMID- 18056039
TI  - Perfusion abnormalities in subchondral bone associated with marrow edema,
      osteoarthritis, and avascular necrosis.
AB  - Bone marrow edema is seen in osteoarthritis, avascular necrosis, and other
      clinical conditions including the bone marrow edema syndrome. Bone marrow edema
      is associated with bone pain and may be related to the pathophysiology of
      osteoarthritis. Our hypothesis is that bone marrow edema is associated with a
      reduction in perfusion in subchondral bone, which contributes to focal and
      segmental bone necrosis and cartilage breakdown. We further hypothesize that
      altered fluid dynamics in subchondral bone comprise part of the physicochemical
      environment to which osteocytes are highly sensitive and alter their cytokine
      expression profile in response to changes in fluid flow, pressure, and oxygen
      gradients. We have used contrast-enhanced magnetic resonance imaging with Gd-DTPA
      to characterize changes in subchondral bone perfusion in two relevant and related
      models-the Dunkin-Hartley guinea pig model of osteoarthritis and human bone
      marrow edema associated with osteoarthritis and avascular necrosis.
      Pharmacokinetic modeling was used to extract dynamic parameters of perfusion.
      Representative time-intensity curves are derived, which characterize normal bone
      and bone with marrow edema. Dynamic contrast-enhanced magnetic resonance imaging
      may be a useful tool for the early diagnosis of bone perfusion abnormalities and
      may be used to characterize marrow edema associated with a number of clinical
      conditions. This technique may also shed light on the pathophysiology of
      subchondral perfusion in osteoarthritis and avascular necrosis.

PMID- 18056040
TI  - Orthopedic implant particle-induced tumor necrosis factor-alpha production in
      macrophage-monocyte lineage cells is mediated by nuclear factor of activated T
      cells.
AB  - Wear particles produced from artificial joint prostheses are known to cause
      macrophage-monocyte lineage cells to produce proosteoclastogenic cytokines,
      including tumor necrosis factor (TNF)-alpha. The specific molecular mechanism,
      however, is not yet known. Bioinformatic analysis showed that the promoter region
      of TNF-alpha has several consensus sequences for NFAT binding. Consequently, we
      examined the role of nuclear factor of activated T cells (NFAT) in TNF-alpha
      production. Our investigation has shown that treatment with titanium
      nanoparticles increased TNF-alpha gene expression along with TNF-alpha protein
      secretion in murine macrophage-like RAW264.7 and primary monocyte-macrophage
      cells. Titanium particle-induced TNF-alpha induction was inhibited by VIVIT, a
      peptide inhibitor that targets the calcineurin/NFAT axis, which suggests that
      NFAT mediates metallic particle-induced TNF-alpha expression in monocyte
      macrophage lineage cells.

PMID- 18056041
TI  - ERK signaling regulates macrophage colony-stimulating factor expression induced
      by titanium particles in MC3T3.E1 murine calvarial preosteoblastic cells.
AB  - Periprosthetic osteolysis poses a significant clinical problem for patients who
      have undergone total joint arthroplastic surgeries. It has been widely recognized
      that there is a strong correlation between wear particles from orthopedic
      implants and osteolysis. However, the molecular mechanism underlying osteolysis
      still remains unclear. Although wear particles interact with a mixed cellular
      environment, namely macrophages and immune cells, osteoblasts compose the
      majority of the cell population surrounding orthopedic implants. Osteoblasts are
      also one of the major sources of receptor activator of nuclear factor-kappa beta
      (NF-kappaB) ligand (RANKL), a factor necessary for osteoclastogenesis. However,
      macrophage colony-stimulating factor (M-CSF), another cytokine responsible for
      preosteoclast proliferation, must also be present with RANKL for
      osteoclastogenesis to occur. The purpose of our study is to determine the signal
      transduction pathway by which titanium (Ti) particles, a metallic component of
      many orthopedic implants, induce M-CSF expression in MC3T3.E1 murine calvarial
      preosteoblastic cells. Using reverse transcriptase-polymerase chain reaction (RT
      PCR) and enzyme- linked immunosorbent assay (ELISA), our study demonstrated that
      submicron-sized Ti particles induce M-CSF expression via the extracellular signal
      regulated kinase (ERK) pathway in a dose-dependent manner. Moreover, inhibition
      studies showed that a specific ERK inhibitor, PD98059, significantly
      downregulated M-CSF production. Our results support the hypothesis that submicron
      sized Ti particles can induce M-CSF expression in osteoblasts and thus may have a
      significant role in contributing to the onset of periprosthetic osteolysis.

PMID- 18056042
TI  - Expression of MIG-6, WNT-9A, and WNT-7B during osteoarthritis.
AB  - Although the molecular mechanisms for initiation of cartilage destruction in
      osteoarthritis (OA) are unknown, it has been demonstrated that disruption of
      mitogen-inducible gene 6 (Mig-6) in mice leads to the onset of a degenerative
      joint disease like OA. On this basis, we correlated gene expression of Mig-6 with
      Wnt-9a and Wnt-7b genes; we showed downregulation of Mig-6, Wnt-7b, and Wnt-9a
      during OA, while Wnt-7b was expressed also in osteoblast-like cells. Here we
      suggest that Aggrecan degradation occurs before the downregulation of Mig-6. It
      remains to be proven whether there is any relation between Wnt signaling and
      Aggrecan degradation.

PMID- 18056043
TI  - Calcitonin affects both bone and cartilage: a dual action treatment for
      osteoarthritis?
AB  - Osteoarthritis (OA) is the most common form of degenerative joint diseases and a
      major cause of disability and impaired quality of life in the elderly. OA is a
      complex disease involving both bone and cartilage properties, and may therefore
      require alternative approaches for treatment. Recent lines of evidence suggest
      that calcitonin acts on both osteoclasts and chondrocytes. The review summarizes
      emerging observations from cell biology to preliminary clinical trials,
      describing possible chondroprotective effects of calcitonin. This review
      summarizes peer-reviewed articles found using predefined search criteria and
      published in the PubMed database before June 2007. In addition, abstracts from
      the OsteoArthritis Research Society International (OARSI) conferences in the time
      period 2000 to 2006 were included. A range of studies, at the cellular level, in
      animal models, and in clinical trials, describe positive effects of calcitonin on
      bone health. Regarding articular cartilage, direct effects of calcitonin on
      chondrocytes on matrix synthesis, as well as inhibition of cartilage degradation,
      have been presented. In addition, clinical evidence for a chondroprotective
      effect of calcitonin is emerging. Several lines of evidence suggest direct
      anabolic effects of calcitonin on articular chondrocytes, resulting in increased
      proteoglycan synthesis. The anticatabolic effects of calcitonin may involve
      induction of cAMP, resulting in attenuation of MMP-mediated cartilage
      degradation. Presently there is limited availability of chondroprotective agents.
      Therefore, the current clinical research on calcitonin is highly anticipated, and
      may prove calcitonin treatment efficacious for the prevention and treatment of
      OA.

PMID- 18056044
TI  - Progress, paradox, and potential: parathyroid hormone research over five decades.
AB  - With the advent of advances in chemical and molecular biology, the structure of
      parathyroid hormone (PTH); the related protein, parathyroid-related protein
      (PTHrP); and their principal receptor (PTH/PTHrP receptor [PTHR1]) were
      established over recent decades. Tests with purified hormonal peptide in humans
      led to the surprising, even paradoxical, finding that PTH can be used
      pharmacologically to build bone, providing a dramatic therapeutic impact on
      osteoporosis. These developments plus recent insights into previously
      unappreciated ligand-receptor conformations that cause prolonged biological
      activation have stimulated the field of calcium and bone biology and posed new
      questions about the role of PTH and PTHrP as well as possible new directions in
      the therapy of osteoporosis and calcium-deficit states.

PMID- 18056046
TI  - Selecting patients for osteoporosis therapy.
AB  - Our goal globally is to better identify individuals at risk for osteoporotic
      fracture so that those at high risk can be treated and unnecessary treatment for
      those at low risk can be avoided. Bone mineral density (BMD) information is not
      sufficient to identify all patients at high risk. Approximately half of patients
      in the community with fractures do not have osteoporosis by the 1994 World Health
      Organization BMD criteria. Furthermore, BMD information based on central DXA is
      not easily accessible worldwide. The use of clinical risk factors with or without
      BMD information will improve gradient of risk and help us better identify
      patients at high risk for fracture. The clinical risk factors identified can be
      integrated to predict a 10-year absolute risk or probability of fracture.
      Intervention thresholds based on absolute risk will be defined regionally based
      on each nation's ability and willingness to pay.

PMID- 18056045
TI  - Bisphosphonates: an update on mechanisms of action and how these relate to
      clinical efficacy.
AB  - The bisphosphonates (BPs) are well established as the treatments of choice for
      disorders of excessive bone resorption, including Paget's disease of bone,
      myeloma and bone metastases, and osteoporosis. There is considerable new
      knowledge about how BPs work. Their classical pharmacological effects appear to
      result from two key properties: their affinity for bone mineral and their
      inhibitory effects on osteoclasts. Mineral binding affinities differ among the
      clinically used BPs and may influence their differential distribution within
      bone, their biological potency, and their duration of action. The inhibitory
      effects of the nitrogen-containing BPs (including alendronate, risedronate,
      ibandronate, and zoledronate) on osteoclasts appear to result from their
      inhibition of farnesyl pyrophosphate synthase (FPPS), a key branch-point enzyme
      in the mevalonate pathway. FPPS generates isoprenoid lipids used for the
      posttranslational modification of small GTP-binding proteins essential for
      osteoclast function. Effects on other cellular pathways, such as preventing
      apoptosis in osteocytes, are emerging as other potentially important mechanisms
      of action. As a class, BPs share several common properties. However, as with
      other classes of drugs, there are obvious chemical, biochemical, and
      pharmacological differences among the various individual BPs. Each BP has a
      unique profile that may help to explain potential important clinical differences
      among the BPs, in terms of speed of onset of fracture reduction, antifracture
      efficacy at different skeletal sites, and the degree and duration of suppression
      of bone turnover. As we approach the 40th anniversary of the discovery of their
      biological effects, there remain further opportunities for using their properties
      for medical purposes.

PMID- 18056047
TI  - Progression of efficacy with ibandronate: a paradigm for the development of new
      bisphosphonates.
AB  - While initial preclinical studies provide an important starting point for dose
      selection, they may not provide adequate information to identify the optimal
      dosage for an extended treatment regimen. Determining the best dose for use in an
      extended dosing regimen requires ongoing development, illustrated best with the
      bisphosphonate, ibandronate. As mandated for regulatory purposes, the daily oral
      regimen of ibandronate was proven effective in significantly reducing the rate of
      new vertebral fractures assessed prospectively, and nonvertebral fractures in a
      high-risk population, assessed retrospectively. Extended dosing regimens, namely
      monthly and quarterly intravenous formulations, were developed subsequently to
      improve the convenience and enhance persistence, while maintaining or increasing
      efficacy. The continuing and progressive evolution of data led to the
      understanding that extension of drug-free interval requires higher annual
      cumulative skeletal exposures (ACE), which were not simply numerical multipliers
      of the interval and daily dose. For ibandronate, this led to dose selection for
      the oral monthly 150 mg (ACE 10.8 mg) and intravenous quarterly 3 mg (ACE 12 mg)
      formulations that proved superior in increasing bone mineral density (BMD)
      compared with oral daily 2.5 mg (ACE 5.5 mg) ibandronate. Pooling data from
      clinical trials with high ACE regimens (monthly and quarterly) led to the
      evolution of statistical evidence for a reduction in clinical and nonvertebral
      fractures with ibandronate. The ibandronate story should serve as an important
      future paradigm for bisphosphonate development.

PMID- 18056048
TI  - Rationale for using nitric oxide donor therapy for prevention of bone loss and
      treatment of osteoporosis in humans.
AB  - Nitric oxide (NO) is a ubiquitous molecule involved in most cellular functions.
      While osteocytes communicate between bone cells, diffusible small molecules-H(+)
      and NO-are involved in short-term regulation of bone metabolism. Studies
      conducted over the past two decades have demonstrated the regulatory role of NO
      in bone metabolism. Circulating NO products are significantly lower in
      postmenopausal women, and estrogen supplementation restores this. Skeletal
      beneficial effects of estrogen are abolished with NO-synthase enzyme inhibitors,
      suggesting some estrogenic skeletal effects are mediated through NO/cGMP pathway.
      Since estrogen/hormone replacement therapy (HRT) has potential adverse effects,
      supplementing NO directly is sensible. NO is also involved with other cellular
      functions, such as isoprenylation of the Rho GTPase that stimulates Rho-PK (the
      functioning Rho-PK in turn inactivates something that would otherwise turn on the
      BMP-2/Cbfa1-Runx-2 cycle), and likely to be the final common pathway of other
      agents including statins. The first human study using nitroglycerine in the
      prevention of oophorectomy-induced bone loss demonstrated an equivalent efficacy
      to estrogen in the prevention of bone loss. A randomized NIH-funded NOVEL
      clinical study is currently assessing the effectiveness of topically administered
      nitroglycerine in the prevention of postmenopausal bone loss. If efficacy of
      nitroglycerine is confirmed, it may become a highly cost-effective and safe
      alternative therapy to treat osteoporosis. Nitroglycerine has beneficial effects
      in multiple systems, especially the cardiovascular system. If results of this
      study confirm our hypothesis, it is plausible that nitroglycerine therapy may
      supplant estrogen replacement and SERMs in preventing and treating postmenopausal
      osteoporosis.

PMID- 18056049
TI  - Proteasome inhibitors stimulate both bone formation and hair growth by similar
      mechanisms.
AB  - We propose that the remodeling process that occurs in localized areas on
      endosteal bone surfaces and in Haversian canals shares many features in common
      with the mammalian hair cycle. In both, there are phases of resorption or
      regeneration, a transition phase, and then a phase of growth, termed anagen in
      the hair follicle, and formation in the bone remodeling cycle. Furthermore, we
      suggest that these processes both use the same molecular mechanisms, and
      specifically the Hedgehog-BMP-Wnt signal transduction cascades. We have found
      that proteasome inhibitors, which enhance bone formation by effects on these
      cascades, also stimulate anagen induction and hair growth in the murine and human
      hair follicle, and propose they do so by effects on similar or identical
      molecular targets.

PMID- 18056050
TI  - The skeletal dysplasias: clinical-molecular correlations.
AB  - The skeletal dysplasias or osteochondrodysplasias are a clinically and
      genetically heterogeneous group of disorders of bone and/or cartilage. They are
      characterized by abnormalities in pattering, linear growth, differentiation, and
      maintenance of the human skeleton. While they have been considered to be
      generalized disorders of endochondral and/or membranous ossification, the extent
      of their clinical and molecular heterogeneity is still being elucidated. In the
      2006 revision of the International Nosology and Classification of Genetic
      Skeletal Disorders, 372 different conditions were listed in 37 groups defined by
      such molecular, biochemical, and/or radiographic criteria. The evaluation of
      patients with chondrodysplasias mandates a multidisciplinary approach involving
      clinical geneticists, radiologists, molecular biologists, and biochemical
      geneticists for diagnosis, and a host of surgical specialists for management of
      their many complications. Our International Skeletal Dysplasia Registry is a
      worldwide referral center for the skeletal dysplasias, and we have received cases
      from over 3000 physicians from 50 different countries and have been involved in
      the identification of the molecular defect in over 40 disorders involving over 25
      different genes. Instructions on accessing the Registry, using the diagnostic
      services provided and contributing cases for collaborative research can be found
      at http://www.csmc.edu/skeletaldysplasia.

PMID- 18056051
TI  - Gene therapy in musculoskeletal repair.
AB  - Local and regional gene therapy has improved healing in preclinical trials of
      articular and other muculoskeletal conditions. Combinations of cell
      supplementation and cells overexpressing growth factor genes have shown promising
      results for improving cartilage repair, enhancing delayed union of fractures, and
      driving organized tendon repair. Proof of concept has been developed using viral
      vectors, predominantly adenovirus, to deliver growth factor genes, such as BMP-2,
      TGF-beta1, and IGF-I. Integrating vectors, such as retrovirus and lentivirus,
      have improved the duration of gene-induced repair, however, increased risk
      factors have limited broad application. Cartilage repair can be improved using
      chondrocyte or stem cell transplantation with cells expressing IGF-I, BMP-2, or
      FGF-2. In cartilage injury and secondary osteoarthritis models, a combination of
      IL-1 knockdown and growth factor supplementation has restored cartilage matrix
      and stabilized the osteoarthritic process. Ultimately, nonviral vectors may
      provide similar control of catabolic activity in cartilage and synovial
      structures, which may further improve outcome after chondrocyte or mesenchymal
      stem cell (MSC) implantation. MSCs derived from bone marrow, fat, or other
      connective tissues provide a multipotent cell source that may be privileged
      vectors for skeletal gene therapy. MSCs expressing BMP-2, TGF-beta1, LMP-1, IGF
      I, or GDF-5 have enhanced cartilage, bone, and tendon repair. Overall, the field
      of orthopedic gene therapy for enhanced tissue repair has made significant
      preclinical advances. Combining existing cell transplant technology to deliver
      differentiated cells in a minimally invasive way, with genes that improve matrix
      formation, provides a manageable protocol for a persisting anabolic impact.

PMID- 18056052
TI  - Effects of adrenal steroids on the bone metabolism of children with congenital
      adrenal hyperplasia.
AB  - The primary treatment for patients with congenital adrenal hyperplasia (CAH) due
      to 21-hydroxylase deficiency (21OHD) is glucocorticoid replacement therapy, which
      at supraphysiologic levels can result in diminished bone accrual and lead to
      osteopenia and osteoporosis. Unlike other diseases treated with chronic
      glucocorticoid therapy, previous studies of patients with 21OHD have not
      demonstrated a detrimental effect of glucocorticoid treatment on bone mineral
      density (BMD). It has been postulated that the elevated androgens typically found
      in these patients have a protective effect on bone integrity, but the precise
      mechanism remains unknown. We propose that the inhibitory effect of
      corticosteroid therapy on bone formation is counteracted by estrogen's effect on
      bone resorption through the RANK-L/osteoprotegerin (OPG) system. A better
      understanding of the mechanism by which patients with 21OHD are protected against
      bone loss may lead to novel therapeutic measures to prevent or treat osteopenia
      and osteoporosis in other conditions, including postmenopausal women.

PMID- 18056054
TI  - Nurse plants vs. nurse objects: effects of woody plants and rocky cavities on the
      recruitment of the Pilosocereus leucocephalus columnar cactus.
AB  - BACKGROUND AND AIMS: Most studies on cactus recruitment have focused on the role
      of woody plants as seedling facilitators. Although the spatial association of
      cacti with objects had been described, the mechanisms underlying this association
      remain unknown. The aims of this study were to identify which mechanisms
      facilitate the establishment of a columnar cactus under the shade and protection
      of objects and to compare these mechanisms with those involved in plant-plant
      facilitation. METHODS: Three split-split-plot field experiments were conducted to
      compare the effects of two microhabitats (inside rocky cavities and beneath plant
      canopies) on seed removal, germination, seedling survivorship and dry weight.
      Flat, open spaces were used as the control. For each microhabitat, the effect of
      seed or seedling protection and substrate limitation were explored; aboveground
      microclimate and some soil properties were also characterized. KEY RESULTS: The
      permanence of superficial seeds was greater inside rocky cavities than beneath
      woody plant canopies or on flat, open areas. Germination was similar in cavities
      and beneath plant canopies, but significantly higher than on flat, open areas.
      Seedling survivorship was greater beneath plant canopies than inside cavities or
      on flat, open spaces. CONCLUSIONS: The mechanisms of plant facilitation are
      different from those of object facilitation. There are seed-seedling conflicts
      involved in the recruitment of P. leucocephalus: nurse plants favour mainly
      seedling survivorship by providing a suitable microenvironment, while nurse
      objects mainly favour seed permanence, by protecting them from predators.

PMID- 18056053
TI  - PTHrP and tumorigenesis: is there a role in prognosis?
AB  - The role of parathyroid hormone-related peptide (PTHrP) in the regulation of
      hypercalcemia in patients with malignancies is well studied, but whether its
      expression in tumor tissue correlates with tumor progression is not clear at
      present. The majority of tumors that metastasize to the bone produce PTHrP, and
      PTHrP expression correlates with skeletal localization of tumors. About 95% of
      colorectal adenocarcinomas overexpress PTHrP mRNA and protein, and the expression
      level is higher in poorly differentiated than in well-differentiated
      adenocarcinomas. However, there is some controversy at present about the
      prognostic significance of PTHrP expression on primary tumor cells, and studies
      suggest that there might be tissue-specific responses. We will briefly present
      here existing evidences that suggest that the expression of PTHrP in the primary
      tumor tissue could have both positive and/or negative impact on tumor progression
      and clinical outcome of the disease.

PMID- 18056055
TI  - Timing of canopy closure influences carbon translocation and seed production of
      an understorey herb, Trillium apetalon (Trilliaceae).
AB  - BACKGROUND AND AIMS: The light availability on a temperate, deciduous-forest
      floor varies greatly, reflecting the seasonal leaf dynamics of the canopy trees.
      The growth and/or reproductive activity of understorey plants should be
      influenced by the length of the high-irradiance period from snowmelt to canopy
      closure. The aim of the present study was to clarify how spring-blooming species
      regulate the translocation of photosynthetic products to current reproduction and
      storage organs during a growing season in accordance with the changing light
      conditions. METHODS: Growth pattern, net photosynthetic rate, seed production,
      and shoot and flower production in the next year of Trillium apetalon were
      compared between natural and experimentally shaded conditions. Furthermore,
      translocation of current photosynthetic products within plants was assessed by a
      labelled carbon-chase experiment. KEY RESULTS: During the high-irradiance period,
      plants showed high photosynthetic ability, in which current products were
      initially used for shoot growth, then reserved in the rhizome. Carbon
      translocation to developing fruit occurred after canopy closure, but this was
      very small due to low photosynthetic rates under the darker conditions. The
      shading treatment in the early season advanced the time of carbon translocation
      to fruit, but reduced seed production in the current year and flower production
      of the next year. CONCLUSIONS: Carbon translocation to the storage organ had
      priority over seed production under high-irradiance conditions. A shortened
      bright period due to early canopy closure effectively restricts carbon
      assimilation, which greatly reduces subsequent reproductive output owing to low
      photosynthetic products for fruit development and small carbon storage for future
      reproduction. As populations of this species are maintained by seedling
      recruitment, acceleration of canopy closure timing may influence the maintenance
      and dynamics of populations.

PMID- 18056056
TI  - Elaiophore structure and oil secretion in flowers of Oncidium trulliferum Lindl.
      and Ornithophora radicans (Rchb.f.) Garay & Pabst (Oncidiinae: Orchidaceae).
AB  - BACKGROUND AND AIMS: Many orchid flowers have glands called elaiophores and these
      reward pollinating insects with oil. In contrast to other reward-producing
      structures such as nectaries, the anatomy of the elaiophore and the process of
      oil secretion have not been extensively studied. In this paper, elaiophore
      structure is described for two members of Oncidiinae, Oncidium trulliferum Lindl.
      and Ornithophora radicans (Rchb.f.) Garay & Pabst. METHODS: Elaiophores of both
      species were examined using light microscopy, scanning electron microscopy and
      transmission electron microscopy. KEY RESULTS AND CONCLUSIONS: In flowers of
      Oncidium trulliferum and Ornithophora radicans, oil is secreted by
      morphologically distinct elaiophores associated with the labellar callus.
      However, in O. trulliferum, elaiophores also occur on the lateral lobes of the
      labellum. In both these species, the epithelial elaiophores are composed of a
      single layer of palisade-like epidermal cells and a distinct subepithelial layer.
      Secretory elaiophore cells may contain numerous, starchless plastids,
      mitochondria and smooth endoplasmic reticulum profiles. In O. trulliferum, the
      cytoplasm contains myelin-like figures but these are absent from O. radicans. In
      the former species, cavities occur in the cell wall and these presumably
      facilitate the passage of oil onto the elaiophore surface. In O. radicans, the
      accumulation of oil between the outer tangential wall and the cuticle causes the
      latter to become distended. Since it is probable that the full discharge of oil
      from the elaiophores of O. radicans occurs only when the cuticle is ruptured by a
      visiting insect, this may contribute towards pollinator specificity. The
      structure of the elaiophore in these species resembles both that found in
      previously investigated species of Oncidiinae and that of certain members of the
      Malpighiaceae.

PMID- 18056058
TI  - Inclusion and exclusion: the politics of history, difference, and medical
      research.

PMID- 18056057
TI  - Comparative proteomics profiling of a phospholamban mutant mouse model of dilated
      cardiomyopathy reveals progressive intracellular stress responses.
AB  - Defective mobilization of Ca2+ by cardiomyocytes can lead to cardiac
      insufficiency, but the causative mechanisms leading to congestive heart failure
      (HF) remain unclear. In the present study we performed exhaustive global
      proteomics surveys of cardiac ventricle isolated from a mouse model of
      cardiomyopathy overexpressing a phospholamban mutant, R9C (PLN-R9C), and
      exhibiting impaired Ca2+ handling and death at 24 weeks and compared them with
      normal control littermates. The relative expression patterns of 6190 high
      confidence proteins were monitored by shotgun tandem mass spectrometry at 8, 16,
      and 24 weeks of disease progression. Significant differential abundance of 593
      proteins was detected. These proteins mapped to select biological pathways such
      as endoplasmic reticulum stress response, cytoskeletal remodeling, and apoptosis
      and included known biomarkers of HF (e.g. brain natriuretic peptide/atrial
      natriuretic factor and angiotensin-converting enzyme) and other indicators of
      presymptomatic functional impairment. These altered proteomic profiles were
      concordant with cognate mRNA patterns recorded in parallel using high density
      mRNA microarrays, and top candidates were validated by RT-PCR and Western
      blotting. Mapping of our highest ranked proteins against a human diseased explant
      and to available data sets indicated that many of these proteins could serve as
      markers of disease. Indeed we showed that several of these proteins are
      detectable in mouse and human plasma and display differential abundance in the
      plasma of diseased mice and affected patients. These results offer a systems-wide
      perspective of the dynamic maladaptions associated with impaired Ca2+ homeostasis
      that perturb myocyte function and ultimately converge to cause HF.

PMID- 18056059
TI  - Incomplete nuclear transformation of human spermatozoa in oligo-astheno
      teratospermia: characterization by indirect immunofluorescence of chromatin and
      thiol status.
AB  - BACKGROUND Sperm heterogeneity in the human, as observed in oligo-astheno
      teratozoospermia (OAT), is associated with hypospermatogenesis. METHODS The
      chromatin of sperm from OAT and normospermic males was characterized with
      antibodies specific for nucleosomes, the histone H3.1/H3.2 isoform, histone TH2B,
      apoptosis-associated H4 acetylation (KM-2) and protamines. Subsequently, sperm
      samples were stained with the thiol-specific fluorochrome monobromobimane (mBBr)
      before and after reduction with dithiotreitol (DTT) as most thiol groups reside
      in the cysteine-rich protamines. We also used fluorescence-activated cell sorter
      (FACS) for sperm histograms and sorting for high or low free and total thiol
      levels. These fractions were further analysed for DNA damage with the TdT-UTP
      nick end-labelling (TUNEL) assay. RESULTS OAT sperm nuclei stained higher for
      nucleosomes and KM2-epitopes, and lower for TH2B. For free, and total, thiol
      groups, OAT sperm were characterized by biphasic distributions, reflecting
      incomplete thiol oxidation as well as overoxidation, and possibly reduced
      protamine contents. The TUNEL assay on sperm subfractions, for both control and
      OAT sperm, revealed that a lower level of free thiol groups is associated with a
      higher TUNEL incidence, and this relationship was also found for total thiol
      levels. Hence, both overoxidation and a low total number of thiol groups
      predestine for sperm apoptosis. CONCLUSIONS Chromatin characteristics reflecting
      an incomplete nucleosome to protamine remodelling were found in subfertile males.
      Sperm apoptosis is related to both incomplete remodelling and protamine
      overoxidation.

PMID- 18056060
TI  - Mouse and human spermatozoa can be freeze-dried without damaging their
      chromosomes.
AB  - BACKGROUND: Although mouse spermatozoa can be freeze-dried without losing their
      reproductive capacity, the technique needs further improvements to reduce the
      incidence of chromosomal damage to spermatozoa. Effects of freeze-drying on human
      spermatozoa are unknown. METHODS: Mouse spermatozoa were suspended in a Tris
      buffered EGTA solution briefly (10 min at 37 degrees C) or for 1-7 days at 4
      degrees C before freeze-drying. Freeze-dried spermatozoa were maintained for up
      to 1 year at 4 degrees C before injection. Sperm chromosomes were examined during
      the first mitosis (cleavage) of zygotes. The ability of sperm to support embryo
      development was assessed by examining mid-gestation fetuses (Day 14) after
      transfer of 2-cell embryos to surrogate mothers. Chromosome integrity of freeze
      dried human spermatozoa was examined by injecting individual spermatozoa into
      mouse oocytes which were previously enucleated. RESULTS: When mouse spermatozoa
      were freeze-dried immediately after suspension in Tris-buffered EGTA solution,
      only c.40% had normal chromosomes. When the mouse spermatozoa were kept in the
      same solution for 3-7 days before freeze-drying, 85-95% had normal chromosomes
      and they were able to support embryo development better than those which were in
      the solution briefly (P < 0.05). Freeze-dried human spermatozoa well maintained
      their chromosomes regardless of the duration of pre-freeze-drying incubation of
      spermatozoa in the Tris-buffered EGTA solution. CONCLUSIONS: Prior incubation of
      mouse spermatozoa in Tris-buffered EGTA solution for several days makes sperm
      chromosomes more resistant to freeze-drying. As the consequence, spermatozoa
      freeze-dried this way support embryo development better than those exposed to
      Tris-buffered EGTA solution only briefly. Freeze-dried human spermatozoa well
      maintained their chromosomes without pre-freeze-drying incubation in Tris
      buffered EGTA solution.

PMID- 18056061
TI  - A dangerous arrow.

PMID- 18056062
TI  - Deja vu--a study of duplicate citations in Medline.
AB  - MOTIVATION: Duplicate publication impacts the quality of the scientific corpus,
      has been difficult to detect, and studies this far have been limited in scope and
      size. Using text similarity searches, we were able to identify signatures of
      duplicate citations among a body of abstracts. RESULTS: A sample of 62,213
      Medline citations was examined and a database of manually verified duplicate
      citations was created to study author publication behavior. We found that 0.04%
      of the citations with no shared authors were highly similar and are thus
      potential cases of plagiarism. 1.35% with shared authors were sufficiently
      similar to be considered a duplicate. Extrapolating, this would correspond to
      3500 and 117,500 duplicate citations in total, respectively. AVAILABILITY:
      eTBLAST, an automated citation matching tool, and Deja vu, the duplicate citation
      database, are freely available at http://invention.swmed.edu/ and
      http://spore.swmed.edu/dejavu

PMID- 18056063
TI  - Model-based deconvolution of genome-wide DNA binding.
AB  - MOTIVATION: Chromatin immunoprecipitation followed by hybridization to a genomic
      tiling microarray (ChIP-chip) is a routinely used protocol for localizing the
      genomic targets of DNA-binding proteins. The resolution to which binding sites in
      this assay can be identified is commonly considered to be limited by two factors:
      (1) the resolution at which the genomic targets are tiled in the microarray and
      (2) the large and variable lengths of the immunoprecipitated DNA fragments.
      RESULTS: We have developed a generative model of binding sites in ChIP-chip data
      and an approach, MeDiChI, for efficiently and robustly learning that model from
      diverse data sets. We have evaluated MeDiChI's performance using simulated data,
      as well as on several diverse ChIP-chip data sets collected on widely different
      tiling array platforms for two different organisms (Saccharomyces cerevisiae and
      Halobacterium salinarium NRC-1). We find that MeDiChI accurately predicts binding
      locations to a resolution greater than that of the probe spacing, even for
      overlapping peaks, and can increase the effective resolution of tiling array data
      by a factor of 5x or better. Moreover, the method's performance on simulated data
      provides insights into effectively optimizing the experimental design for
      increased binding site localization accuracy and efficacy. AVAILABILITY: MeDiChI
      is available as an open-source R package, including all data, from
      http://baliga.systemsbiology.net/medichi.

PMID- 18056064
TI  - BAGET: a web server for the effortless retrieval of prokaryotic gene context and
      sequence.
AB  - BAGET (Bacterial and Archaeal Gene Exploration Tool) is a web service designed to
      facilitate extraction, by molecular geneticists and phylogeneticists, of specific
      gene and protein sequences from completely determined prokaryotic genomes. Upon
      selection of a particular prokaryotic organism and gene, two levels of visual
      gene context information are provided on a single dynamic page: (i) a graphical
      representation of a user defined portion of the chromosome centered on the gene
      of interest and (ii) the DNA sequence of the query gene, of the immediate
      neighboring genes and the intergenic regions each identified by a consistent
      color code. The aminoacid sequence is provided for protein-coding query genes.
      Query results can be exported as a rich text format (RTF) word processor file for
      printing, archival or further analysis. AVAILABILITY: http://archaea.u
      psud.fr/bin/baget.dll.

PMID- 18056065
TI  - COMPARE, a multi-organism system for cross-species data comparison and transfer
      of information.
AB  - MOTIVATION: COMPARE is a multi-organism web-based resource system designed to
      easily retrieve, correlate and interpret data across species. The COMPARE
      interface provides access to a wide array of information including genomic
      structure, expression data, annotations, pathways and literature links for human
      and three widely studied animal models (zebrafish, Drosophila and mouse). A
      consensus ortholog-finding pipeline combining several ortholog prediction methods
      allows accurate comparisons of data across species and has been utilized to
      transfer information from well studied organisms to more poorly annotated ones.
      AVAILABILITY: http://compare.ibdml.univ-mrs.fr.

PMID- 18056066
TI  - OBO Explorer: an editor for Open Biomedical Ontologies in OWL.
AB  - MOTIVATION: To clarify the semantics, and take advantage of tools and algorithms
      developed for the Semantic Web, a mapping from the Open Biomedical Ontologies
      (OBO) format to the Web Ontology Language (OWL) has been established. We present
      an ontology editor that allows end users to work directly with this OWL
      representation of OBO format ontologies. AVAILABILITY:
      http://www.aiai.ed.ac.uk/project/cobra-ct.

PMID- 18056067
TI  - An integrated system for studying residue coevolution in proteins.
AB  - Residue coevolution has recently emerged as an important concept, especially in
      the context of protein structures. While a multitude of different functions for
      quantifying it have been proposed, not much is known about their relative
      strengths and weaknesses. Also, subtle algorithmic details have discouraged
      implementing and comparing them. We addressed this issue by developing an
      integrated online system that enables comparative analyses with a comprehensive
      set of commonly used scoring functions, including Statistical Coupling Analysis
      (SCA), Explicit Likelihood of Subset Variation (ELSC), mutual information and
      correlation-based methods. A set of data preprocessing options are provided for
      improving the sensitivity and specificity of coevolution signal detection,
      including sequence weighting, residue grouping and the filtering of sequences,
      sites and site pairs. A total of more than 100 scoring variations are available.
      The system also provides facilities for studying the relationship between
      coevolution scores and inter-residue distances from a crystal structure if
      provided, which may help in understanding protein structures. AVAILABILITY: The
      system is available at http://coevolution.gersteinlab.org. The source code and
      JavaDoc API can also be downloaded from the web site.

PMID- 18056068
TI  - KEGGanim: pathway animations for high-throughput data.
AB  - MOTIVATION: Gene expression analysis with microarrays has become one of the most
      widely used high-throughput methods for gathering genome-wide functional data.
      Emerging -omics fields such as proteomics and interactomics introduce new
      information sources. With the rise of systems biology, researchers need to
      concentrate on entire complex pathways that guide individual genes and related
      processes. Bioinformatics methods are needed to link the existing knowledge about
      pathways with the growing amounts of experimental data. RESULTS: We present
      KEGGanim, a novel web-based tool for visualizing experimental data in biological
      pathways. KEGGanim produces animations and images of KEGG pathways using public
      or user uploaded high-throughput data. Pathway members are coloured according to
      experimental measurements, and animated over experimental conditions. KEGGanim
      visualization highlights dynamic changes over conditions and allows the user to
      observe important modules and key genes that influence the pathway. The simple
      user interface of KEGGanim provides options for filtering genes and experimental
      conditions. KEGGanim may be used with public or private data for 14 organisms
      with a large collection of public microarray data readily available. Most common
      gene and protein identifiers and microarray probesets are accepted for
      visualization input. AVAILABILITY: http://biit.cs.ut.ee/KEGGanim/.

PMID- 18056069
TI  - Automated manipulation of systems biology models using libSBML within Taverna
      workflows.
AB  - Many data manipulation processes involve the use of programming libraries. These
      processes may beneficially be automated due to their repeated use. A convenient
      type of automation is in the form of workflows that also allow such processes to
      be shared amongst the community. The Taverna workflow system has been extended to
      enable it to use and invoke Java classes and methods as tasks within Taverna
      workflows. These classes and methods are selected for use during workflow
      construction by a Java Doclet application called the API Consumer. This selection
      is stored as an XML file which enables Taverna to present the subset of the API
      for use in the composition of workflows. The ability of Taverna to invoke Java
      classes and methods is demonstrated by a workflow in which we use libSBML to map
      gene expression data onto a metabolic pathway represented as a SBML model.
      AVAILABILITY: Taverna and the API Consumer application can be freely downloaded
      from http://taverna.sourceforge.net

PMID- 18056070
TI  - Serum intact parathyroid hormone in diabetic patients on haemodialysis: what is
      the treatment goal?

PMID- 18056071
TI  - Bone disease after renal transplantation.

PMID- 18056072
TI  - Posterior reversible encephalopathy syndrome in systemic lupus erythematosus.

PMID- 18056074
TI  - Functional gene losses occur with minimal size reduction in the plastid genome of
      the parasitic liverwort Aneura mirabilis.
AB  - Aneura mirabilis is a parasitic liverwort that exploits an existing mycorrhizal
      association between a basidiomycete and a host tree. This unusual liverwort is
      the only known parasitic seedless land plant with a completely nonphotosynthetic
      life history. The complete plastid genome of A. mirabilis was sequenced to
      examine the effect of its nonphotosynthetic life history on plastid genome
      content. Using a partial genomic fosmid library approach, the genome was
      sequenced and shown to be 108,007 bp with a structure typical of green plant
      plastids. Comparisons were made with the plastid genome of Marchantia polymorpha,
      the only other liverwort plastid sequence available. All ndh genes are either
      absent or pseudogenes. Five of 15 psb genes are pseudogenes, as are 2 of 6 psa
      genes and 2 of 6 pet genes. Pseudogenes of cysA, cysT, ccsA, and ycf3 were also
      detected. The remaining complement of genes present in M. polymorpha is present
      in the plastid of A. mirabilis with intact open reading frames. All pseudogenes
      and gene losses co-occur with losses detected in the plastid of the parasitic
      angiosperm Epifagus virginiana, though the latter has functional gene losses not
      found in A. mirabilis. The plastid genome sequence of A. mirabilis represents
      only the second liverwort, and first mycoheterotroph, to have its plastid genome
      sequenced. We observed a pattern of genome evolution congruent with functional
      gene losses in parasitic angiosperms but suggest that its plastid genome
      represents a genome in the early stages of decay following the relaxation of
      selection pressures.

PMID- 18056073
TI  - Specific enrichment of miRNAs in Arabidopsis thaliana infected with Tobacco
      mosaic virus.
AB  - RNA silencing is a broadly conserved machinery and is involved in many biological
      events. Small RNAs are key molecules in RNA silencing pathway that guide sequence
      specific gene regulations and chromatin modifications. The silencing machinery
      works as an anti-viral defense in virus-infected plants. It is generally accepted
      that virus-specific small interfering (si) RNAs bind to the viral genome and
      trigger its cleavage. Previously, we have cloned and obtained sequences of small
      RNAs from Arabidopsis thaliana infected or uninfected with crucifer Tobacco
      mosaic virus. MicroRNAs (miRNAs) accumulated to a higher percentage of total
      small RNAs in the virus-infected plants. This was partly because the viral
      replication protein binds to the miRNA/miRNA* duplexes. In the present study, we
      mapped the sequences of small RNAs other than virus-derived siRNAs to the
      Arabidopsis genome and assigned each small RNA. It was demonstrated that only
      miRNAs increased as a result of viral infection. Furthermore, some newly
      identified miRNAs and miRNA candidates were found from the virus-infected plants
      despite a limited number of examined sequences. We propose that it is
      advantageous to use virus-infected plants as a source for cloning and identifying
      new miRNAs.

PMID- 18056075
TI  - Evolutionary rate variation at multiple levels of biological organization in
      plant mitochondrial DNA.
AB  - We examined patterns of mitochondrial polymorphism and divergence in the
      angiosperm genus Silene and found substantial variation in evolutionary rates
      among species and among lineages within species. Moreover, we found corresponding
      differences in the amount of polymorphism within species. We argue that, along
      with our earlier findings of rate variation among genes, these patterns of rate
      heterogeneity at multiple phylogenetic scales are most likely explained by
      differences in underlying mutation rates. In contrast, no rate variation was
      detected in nuclear or chloroplast loci. We conclude that mutation rate
      heterogeneity is a characteristic of plant mitochondrial sequence evolution at
      multiple biological scales and may be a crucial determinant of how much
      polymorphism is maintained within species. These dramatic patterns of variation
      raise intriguing questions about the mechanisms driving and maintaining mutation
      rate heterogeneity in plant mitochondrial genomes. Additionally, they should
      alter our interpretation of many common phylogenetic and population genetic
      analyses.

PMID- 18056076
TI  - Adaptive evolution of proteins secreted during sperm maturation: an analysis of
      the mouse epididymal transcriptome.
AB  - A common pattern observed in molecular evolution is that reproductive genes tend
      to evolve rapidly. However, most previous studies documenting this rapid
      evolution are based on genes expressed in just a few male reproductive organs. In
      mammals, sperm become motile and capable of fertilization only after leaving the
      testis, during their transit through the epididymis. Thus, genes expressed in the
      epididymis are expected to play important roles in male fertility. Here, we
      performed evolutionary genetic analyses on the epididymal transcriptome of mice.
      Overall, epididymis-expressed genes showed evidence of strong evolutionary
      constraint, a finding that contrasts with most previous analyses of genes
      expressed in other male reproductive organs. However, a subset of epididymis
      specialized, secreted genes showed several signatures of adaptive evolution,
      including an increased rate of nonsynonymous evolution. Furthermore, this subset
      of genes was overrepresented on the X chromosome. Immunity and protein
      modification functions were significantly overrepresented among epididymis
      specialized, secreted genes. These analyses identified a group of genes likely to
      be important in male reproductive success.

PMID- 18056077
TI  - Overlapping activator sequences determined for two oppositely oriented promoters
      in halophilic Archaea.
AB  - Transcription of the genomic region involved in gas vesicle formation in
      Halobacterium salinarum (p-vac) and Haloferax mediterranei (mc-vac) is driven by
      two divergent promoters, P(A) and P(D), separated by only 35 nt. Both promoters
      are activated by the transcription activator GvpE which in the case of P(mcA)
      requires a 20-nt sequence (UAS) consisting of two conserved 8-nt sequence
      portions located upstream of BRE. Here, we determined the two UAS elements in the
      promoter region of p-vac by scanning mutageneses using constructs containing
      P(pD) (without P(pA)) fused to the bgaH reporter gene encoding an enzyme with
      beta-galactosidase activity, or the dual reporter construct pApD with P(pD) fused
      to bgaH and P(pA) to an altered version of gvpA. The two UAS elements found
      exhibited a similar extension and distance to BRE as previously determined for
      the UAS in P(mcA). Their distal 8-nt portions almost completely overlapped in the
      centre of P(pD)-P(pA), and mutations in this region negatively affected the GvpE
      mediated activation of both promoters. Any alteration of the distance between BRE
      and UAS resulted in the loss of the GvpE activation, as did a complete
      substitution of the proximal 8-nt portion, underlining that a close location of
      UAS and BRE was very important.

PMID- 18056078
TI  - The interaction of mammalian mitochondrial translational initiation factor 3 with
      ribosomes: evolution of terminal extensions in IF3mt.
AB  - Mammalian mitochondrial initiation factor 3 (IF3(mt)) has a central region with
      homology to bacterial IF3. This homology region is preceded by an N-terminal
      extension and followed by a C-terminal extension. The role of these extensions on
      the binding of IF3(mt) to mitochondrial small ribosomal subunits (28S) was
      studied using derivatives in which the extensions had been deleted. The K(d) for
      the binding of IF3(mt) to 28S subunits is approximately 30 nM. Removal of either
      the N- or C-terminal extension has almost no effect on this value. IF3(mt) has
      very weak interactions with the large subunit of the mitochondrial ribosome (39S)
      (K(d) = 1.5 muM). However, deletion of the extensions results in derivatives with
      significant affinity for 39S subunits (K(d) = 0.12-0.25 muM). IF3(mt) does not
      bind 55S monosomes, while the deletion derivative binds slightly to these
      particles. IF3(mt) is very effective in dissociating 55S ribosomes. Removal of
      the N-terminal extension has little effect on this activity. However, removal of
      the C-terminal extension leads to a complex dissociation pattern due to the high
      affinity of this derivative for 39S subunits. These data suggest that the
      extensions have evolved to ensure the proper dissociation of IF3(mt) from the 28S
      subunits upon 39S subunit joining.

PMID- 18056079
TI  - Identifying foldable regions in protein sequence from the hydrophobic signal.
AB  - Structural genomics initiatives aim to elucidate representative 3D structures for
      the majority of protein families over the next decade, but many obstacles must be
      overcome. The correct design of constructs is extremely important since many
      proteins will be too large or contain unstructured regions and will not be
      amenable to crystallization. It is therefore essential to identify regions in
      protein sequences that are likely to be suitable for structural study. Scooby
      Domain is a fast and simple method to identify globular domains in protein
      sequences. Domains are compact units of protein structure and their correct
      delineation will aid structural elucidation through a divide-and-conquer
      approach. Scooby-Domain predictions are based on the observed lengths and
      hydrophobicities of domains from proteins with known tertiary structure. The
      prediction method employs an A*-search to identify sequence regions that form a
      globular structure and those that are unstructured. On a test set of 173 proteins
      with consensus CATH and SCOP domain definitions, Scooby-Domain has a sensitivity
      of 50% and an accuracy of 29%, which is better than current state-of-the-art
      methods. The method does not rely on homology searches and, therefore, can
      identify previously unknown domains.

PMID- 18056080
TI  - Measuring the dynamic surface accessibility of RNA with the small paramagnetic
      molecule TEMPOL.
AB  - The surface accessibility of macromolecules plays a key role in modulating
      molecular recognition events. RNA is a complex and dynamic molecule involved in
      many aspects of gene expression. However, there are few experimental methods
      available to measure the accessible surface of RNA. Here, we investigate the
      accessible surface of RNA using NMR and the small paramagnetic molecule TEMPOL.
      We investigated two RNAs with known structures, one that is extremely stable and
      one that is dynamic. For helical regions, the TEMPOL probing data correlate well
      with the predicted RNA surface, and the method is able to distinguish subtle
      variations in atom depths, such as the relative accessibility of pyrimidine
      versus purine aromatic carbon atoms. Dynamic motions are also detected by TEMPOL
      probing, and the method accurately reports a previously characterized pH
      dependent conformational transition involving formation of a protonated C-A pair
      and base flipping. Some loop regions are observed to exhibit anomalously high
      accessibility, reflective of motions that are not evident within the ensemble of
      NMR structures. We conclude that TEMPOL probing can provide valuable insights
      into the surface accessibility and dynamics of RNA, and can also be used as an
      independent means of validating RNA structure and dynamics in solution.

PMID- 18056081
TI  - Nepsilon-formylation of lysine is a widespread post-translational modification of
      nuclear proteins occurring at residues involved in regulation of chromatin
      function.
AB  - Post-translational modification of histones and other chromosomal proteins
      regulates chromatin conformation and gene activity. Methylation and acetylation
      of lysyl residues are among the most frequently described modifications in these
      proteins. Whereas these modifications have been studied in detail, very little is
      known about a recently discovered chemical modification, the N(epsilon)-lysine
      formylation, in histones and other nuclear proteins. Here we mapped, for the
      first time, the sites of lysine formylation in histones and several other nuclear
      proteins. We found that core and linker histones are formylated at multiple lysyl
      residues located both in the tails and globular domains of histones. In core
      histones, formylation was found at lysyl residues known to be involved in
      organization of nucleosomal particles that are frequently acetylated and
      methylated. In linker histones and high mobility group proteins, multiple
      formylation sites were mapped to residues with important role in DNA binding.
      N(epsilon)-lysine formylation in chromosomal proteins is relatively abundant,
      suggesting that it may interfere with epigenetic mechanisms governing chromatin
      function, which could lead to deregulation of the cell and disease.

PMID- 18056082
TI  - Ab initio thermodynamic modeling of distal multisite transcription regulation.
AB  - Transcription regulation typically involves the binding of proteins over long
      distances on multiple DNA sites that are brought close to each other by the
      formation of DNA loops. The inherent complexity of assembling regulatory
      complexes on looped DNA challenges the understanding of even the simplest genetic
      systems, including the prototypical lac operon. Here we implement a scalable
      approach based on thermodynamic molecular properties to model ab initio systems
      regulated through multiple DNA sites with looping. We show that this approach
      applied to the lac operon accurately predicts the system behavior for a wide
      range of cellular conditions, which include the transcription rate over five
      orders of magnitude as a function of the repressor concentration for wild type
      and all seven combinations of deletions of three operators, as well as the
      observed induction curves for cells with and without active catabolite activator
      protein. Our results provide new insights into the detailed functioning of the
      lac operon and reveal an efficient avenue to incorporate the required underlying
      molecular complexity into fully predictive models of gene regulation.

PMID- 18056083
TI  - Regulating gene expression in human leukemia cells using light-activated
      oligodeoxynucleotides.
AB  - Light-activated antisense oligodeoxynucleotides (asODNs) were developed to
      control the degradation of target mRNA in living cells by RNase H. A 20-mer asODN
      previously shown to target c-myb, a hematopoietic transcription factor, was
      covalently attached via a photocleavable linker (PL) to partially complementary
      20-mer sense strands (sODNs). In the 'caged' state, the sODN blocked
      hybridization of the asODN to c-myb mRNA. Six asODN-PL-sODN conjugates, C1-C6,
      were synthesized. C5, with twelve complementary bases, gave the largest decrease
      in melting temperature (T(m)) upon UV irradiation (DeltaT(m) = -29 degrees C).
      The most thermally stable conjugate, C6 (T(m) = 84 degrees C), gave the lowest
      background RNase H activity, with just 8.6% degradation of an RNA 40-mer after 1
      h incubation. In biochemical assays with C6, RNA digestion increased 10-fold 10
      min after UV irradiation. Finally, phosphorothioated analogs S-C5 and S-C6 were
      synthesized to test activity in cultured K562 (human leukemia) cells. No
      knockdown of c-myb mRNA or protein was observed with intact S-C5 or S-C6, whereas
      more than half of c-myb mRNA was degraded 24 h after photoactivation. Two-fold
      photomodulation of c-MYB protein levels was also observed with S-C5. However, no
      photomodulation of c-MYB protein levels was observed with S-C6, perhaps due to
      the greater stability of this duplex.

PMID- 18056084
TI  - TreeFam: 2008 Update.
AB  - TreeFam (http://www.treefam.org) was developed to provide curated phylogenetic
      trees for all animal gene families, as well as orthologue and paralogue
      assignments. Release 4.0 of TreeFam contains curated trees for 1314 families and
      automatically generated trees for another 14,351 families. We have expanded
      TreeFam to include 25 fully sequenced animal genomes, as well as four genomes
      from plant and fungal outgroup species. We have also introduced more accurate
      approaches for automatically grouping genes into families, for building
      phylogenetic trees, and for inferring orthologues and paralogues. The user
      interface for viewing phylogenetic trees and family information has been
      improved. Furthermore, a new perl API lets users easily extract data from the
      TreeFam mysql database.

PMID- 18056086
TI  - How cognition modulates affective responses to taste and flavor: top-down
      influences on the orbitofrontal and pregenual cingulate cortices.
AB  - How cognition influences the affective brain representations of the taste and
      flavor of a food is important not only for understanding top-down influences in
      the brain, but also in relation to the topical issues of appetite control and
      obesity. We found using functional magnetic resonance imaging that activations
      related to the affective value of umami taste and flavor (as shown by
      correlations with pleasantness ratings) in the orbitofrontal cortex were
      modulated by word-level descriptors. Affect-related activations to taste were
      modulated in a region that receives from the orbitofrontal cortex, the pregenual
      cingulate cortex, and to taste and flavor in another region that receives from
      the orbitofrontal cortex, the ventral striatum. Affect-related cognitive
      modulations were not found in the insular taste cortex, where the intensity but
      not the pleasantness of the taste was represented. We conclude that top-down
      language-level cognitive effects reach far down into the earliest cortical areas
      that represent the appetitive value of taste and flavor. This is an important way
      in which cognition influences the neural mechanisms that control appetite.

PMID- 18056087
TI  - Combined single-drop and rotating drum dustiness test of fine to nanosize powders
      using a small drum.
AB  - A dustiness test has been developed that performs both a single-drop and a
      continuous rotation test using a 6-g sample. Tests were completed on pigment
      grade and ultrafine TiO2, two grades of corundum (Aloxite), yttrium-stabilized
      zirconia (Y-zirconia) granules, fumed silica, goethite, talc and bentonite. The
      generated particles were quantified by counting and sizing at 1-s time resolution
      using the TSI Fast Mobility Particle Sizer and the TSI Aerodynamic Particle Sizer
      and by collecting the particles on a filter for weighing. The method generated
      reproducible amounts and size distributions of particles. The size distributions
      had two more or less separated size modes >0.9 microm and in addition all
      materials except TiO2 pigment-grade and Aloxite F1200 generated a size mode in
      the range from approximately 100 to approximately 220 nm. Pigment-grade TiO2 had
      the lowest dustiness and ultrafine TiO2 the highest dustiness as measured by
      particle number for both the single-drop and rotation test and as measured by
      mass for both tests combined. The difference was a factor of approximately 300.
      Three types of dust generation rate time profiles were observed; brief initial
      burst (talc, both grades of corundum), decaying rate during rotation period
      (fumed silica, TiO2 ultrafine and pigment grade, bentonite) and constant rate (Y
      zirconia, goethite). These profile types were in agreement with the differences
      in the ratio of amount of particles generated during the single drop to the
      amount generated during the single-drop and rotation test combined. The ratio
      ranged a factor approximately 40. The new test method enables a characterization
      of dustiness with relevance to different user scenarios.

PMID- 18056085
TI  - Familiarity and conceptual priming engage distinct cortical networks.
AB  - Familiarity refers to an explicit recognition experience without any necessary
      retrieval of specific detail related to the episode during which initial learning
      transpired. Prior experience can also implicitly influence subsequent processing
      through a memory phenomenon termed conceptual priming, which occurs without
      explicit awareness of recognition. Resolving current theoretical controversy on
      relationships between familiarity and conceptual priming requires a clarification
      of their neural substrates. Accordingly, we obtained functional magnetic
      resonance images in a novel paradigm for separately assessing neural correlates
      of familiarity and conceptual priming using famous and nonfamous faces.
      Conceptual priming, as shown by more accurate behavioral responses to strongly
      conceptually primed than to weakly conceptually primed faces, was associated with
      activity reductions in left prefrontal cortex, whereas familiarity was associated
      with activity enhancements in right parietal cortex for more-familiar compared
      with less-familiar faces. This neuroimaging evidence implicates separate
      neurocognitive processes operative in explicit stimulus recognition versus
      implicit conceptual priming.

PMID- 18056089
TI  - Causation: a loosely founded concept in epidemiology.

PMID- 18056088
TI  - Research ethics approval: comprehensive mechanisms are essential but not
      available.

PMID- 18056090
TI  - Ethical research.

PMID- 18056091
TI  - Erosion vs. corrosion.

PMID- 18056092
TI  - Amalgam study.

PMID- 18056098
TI  - Perceptions of patients' smiles: a comparison of patients' and dentists'
      opinions.
AB  - BACKGROUND: Little information has been published regarding the difference
      between how patients perceive their own smiles and how dentists view them.
      METHODOLOGY: The authors interviewed 78 consecutively seen patients in a general
      dental practice in Norway about esthetic features of their faces. The patients
      were not actively seeking esthetic treatment. Patients rated themselves using a
      100-point visual analog scale (VAS), and then two dentists (the patients' regular
      dentist and an independent periodontist), working with photographs of the
      patients, used the same VAS in rating the patients' smiles. RESULTS: The average
      age of the patients was 51.2 years (range, 22-84 years). There were 50 women
      (average age, 51.5 years; range, 22-84 years) and 28 men (average age, 52 years;
      range, 30-78 years). Patients' satisfaction with their own smiles reached an
      average of 59.1 (standard deviation [SD], 21.1; range, 5-100) on the VAS. The
      dentists' scores (38.6 and 40.7) were significantly lower than the patients'
      scores. The authors observed poor correlation between the periodontist's scores
      of dentogingival features and the patients' scores. Patients were most satisfied
      with the gingiva when smiling and least satisfied with tooth shade. Patients
      younger than 50 years were most satisfied with their smiles. Patients rated teeth
      and eyes as the most important features in an attractive face. Women gave teeth
      and hair significantly higher scores and head shape lower scores than did men.
      CONCLUSION: Patients' opinions of their own smiles were significantly higher than
      the two clinicians' assessments of their smiles. Dentists should be aware that
      patients who seek esthetic services may have different perceptions of their
      smiles than may patients who do not express such desires.

PMID- 18056099
TI  - A survey of the current approaches to diagnosis and management of oral
      premalignant lesions.
AB  - BACKGROUND: Early diagnosis of oral premalignant lesions (OPLs) and oral squamous
      cell carcinoma facilitates treatment with less aggressive approaches and results
      in a better prognosis. The authors conducted a study to identify current
      practices in the diagnosis and management of these oral lesions by oral medicine
      professionals. METHODS: The authors sent a questionnaire to 176 diplomates of the
      American Board of Oral Medicine and asked them to complete the questionnaires and
      return them by mail. RESULTS: The initial clinical approach taken by most of the
      responders included visual examination, elimination of possible local causes and
      two-week follow-up. Adjuvant clinical tests included toluidine blue, oral brush
      biopsy and exfoliative cytology. If there was no clinical improvement after two
      weeks, most responders recommended that a biopsy be performed. Induration, red
      component, nonhomogeneous surface and ulceration were characteristics of lesions
      that increased the responders' decisions to perform a biopsy. Lesion symptoms and
      location also contributed to their decisions to perform a biopsy. Follow-up more
      frequently than twice a year was recommended for red lesions, lesions with
      histologically confirmed dysplasia or both. Most clinicians recommend a biopsy
      during follow-up of an OPL whenever the lesion changes in appearance.
      CONCLUSIONS: The findings of this survey may provide background for initial
      guidelines to be used by oral practitioners to diagnose and manage OPL.
      Clinicians' awareness of the complexity of OPL diagnosis and management is
      important, and referral to an experienced provider is recommended.

PMID- 18056100
TI  - Pain experienced by patients undergoing different periodontal therapies.
AB  - BACKGROUND: The authors assessed the levels of postoperative pain, postoperative
      dentin hypersensitivity and discomfort patients experienced during various
      periodontal treatments by using a visual analog scale (VAS). They aimed to
      determine whether VAS scores could be predicted by patient's age and sex and to
      evaluate the factors associated with the pain. SUBJECTS AND METHODS: The study
      was carried out with 56 patients who had chronic periodontitis. Using a split
      mouth design, the authors selected one quadrant in each patient and treated it
      with scaling and root planing (SRP). They treated other quadrants with the
      surgical therapies of modified Widman flap (MWF), flap with osseous resection
      (OF) and gingivectomy (GV), depending on the patient's diagnosis and treatment
      needs. They measured patients' discomfort during periodontal treatments,
      postoperative pain and postoperative dentin hypersensitivity by asking patients
      to mark a VAS. RESULTS: The authors' analysis showed no statistically significant
      differences between the patients' discomfort levels associated with the four
      therapy types during periodontal treatment. However, postoperative pain was
      significantly higher for OF (P < .01) and GV (P < .05) procedures than for SRP
      and MWF procedures. All surgical procedures produced significantly more dentin
      hypersensitivity than did nonsurgical therapy. The analysis showed no
      statistically significant differences between male and female patients'
      discomfort during periodontal treatments. For all periodontal treatments, VAS
      scores decreased with increasing age. CONCLUSIONS: Discomfort during periodontal
      treatments, postoperative pain and postoperative dentin hypersensitivity were
      associated significantly with age, type of therapy and higher scores on Corah's
      Dental Anxiety Scale. CLINICAL IMPLICATIONS: Periodontal treatment is experienced
      as painful by substantial numbers of patients. Therefore, the dentist should
      count the pain responses during and after treatment and estimate the degree of
      pain according to sex, age and therapy type.

PMID- 18056101
TI  - Gingival involvement in Crohn disease.
AB  - BACKGROUND: Although the oral manifestations of Crohn disease are well
      established, there is little specific documentation of the gingival involvement.
      CASE DESCRIPTION: The authors describe four patients with significant gingival
      involvement and identify clinical signs and symptoms of the disease involving the
      gingivae, along with other oral manifestations. Patients had persistent gingival
      lesions manifesting as pustular ulcerations, erythema, swelling and
      cobblestoning. The authors also discuss the differential diagnosis, treatment
      options and prognostic factors. CLINICAL IMPLICATIONS: Patients with gingival
      and/or other oral lesions with or without other constitutional symptoms should be
      evaluated for Crohn disease. Dentists can play a critical role in the early
      diagnosis, and they can help prevent complications and improve the prognosis.

PMID- 18056102
TI  - Salivary gland injury resulting from exposure to radioactive iodine: case
      reports.
AB  - BACKGROUND: Radioactive iodine 131 ((131)I) is an effective treatment for
      differentiated thyroid carcinomas. (131)I targets thyroid tissue and is picked up
      by the salivary glands. Collateral damage results in the development of radiation
      sialadenitis. CASE DESCRIPTION: The authors describe salivary gland injuries that
      developed in two patients who received therapeutic doses of (131)I used to treat
      thyroid carcinoma. Accurate assessment of the glandular damage was achieved via a
      radioisotope study using technetium Tc 99m pertechnetate. CONCLUSION AND CLINICAL
      IMPLICATIONS: In the majority of cases, when a patient receives therapeutic doses
      of (131)I, the patient develops an asymmetric radiation sialadenitis. Obstructive
      symptomatology is to be expected. Oral dryness occurs less often and is related
      directly to high dosages and the passage of time. Clinicians should be aware of
      the condition to avoid unnecessary diagnostic and therapeutic measures.

PMID- 18056103
TI  - Chronic lesions of the gingiva and mucosa.

PMID- 18056104
TI  - In vitro protection against dental erosion afforded by commercially available,
      calcium-fortified 100 percent juices.
AB  - BACKGROUND: Calcium in acidic beverages can decrease a person's risk of
      experiencing dental erosion. The authors compared the pHs and titratable
      acidities of commercially available calcium-fortified and unfortified 100 percent
      juices, and enamel and root surface lesion depths after they were exposed to
      different juices. METHODS: The authors measured the pH and titratable acidity of
      calcium-fortified and unfortified 100 percent juices. They exposed enamel and
      root surfaces to different 100 percent juices for 25 hours and measured lesion
      depths. They used the Spearman rank correlation test and the two-sample t test to
      identify associations between the juices' properties and lesion depths and to
      compare lesion depths between fortified and unfortified juices. RESULTS: The
      authors found that fortifying apple, orange and grapefruit juices with calcium
      prevented enamel erosion and decreased root surface erosion (P < .01). They also
      found that fortifying white grape juice with calcium decreased enamel erosion (P
      < .001) but not root surface erosion. They observed that mean lesion depths were
      greater in root surfaces than in enamel surfaces after exposure to unfortified
      orange juice and all fortified juices (P < .001). CONCLUSIONS: Calcium
      concentrations in commercially available, calcium-fortified 100 percent juices
      are sufficient to decrease and prevent erosion associated with extended exposure
      to a beverage. CLINICAL IMPLICATIONS: People at risk of experiencing erosion
      could decrease their erosion risk by consuming calcium-fortified juices.

PMID- 18056105
TI  - Using extracted teeth for research: the effect of storage medium and
      sterilization on dentin bond strengths.
AB  - BACKGROUND: The Centers for Disease Control and Prevention has adopted guidelines
      for infection control of extracted teeth used for research and teaching,
      requiring that teeth be sterilized before use. The authors conducted a study to
      test the null hypothesis that the storage medium and sterilization method have no
      effect on composite-to-dentin bond strengths. MATERIALS AND METHODS: The authors
      collected 170 bovine incisors, cleaned them and placed them randomly into one of
      six storage media at 37 degrees C for 60 days: distilled water (dH(2)O), 0.9
      percent sodium chloride, 0.5 percent chloramine-T, 5.25 percent sodium
      hypochlorite (NaClO), 2 percent glutaraldehyde and 10 percent formalin. For
      sterilization, they autoclaved a subset of 10 specimens from every sample, while
      they stored another subset of 10 specimens from every sample (except for the 10
      percent formalin sample) in 10 percent formalin for 14 days. The authors then
      embedded the specimens in epoxy and ground flat the facial surface to expose
      middle-depth dentin, which they polished to 600 grit. They used a dental adhesive
      to apply composite to the exposed dentin. The authors tested the composite-to
      dentin shear bond strength 24 hours after bonding. They analyzed the data using
      global analysis of variance and, when appropriate, multiple post hoc tests (P =
      .05). RESULTS: Storage in NaClO resulted in significantly lower bond strength
      than that of the other treatment specimens. Sterilization with the autoclave
      negatively affected the bond strength of specimens stored initially in dH(2)O or
      10 percent formalin, while sterilization with formalin alone had no significant
      effect on bond strengths. CONCLUSIONS: Storing bovine teeth in 5.25 percent NaClO
      may negatively affect composite-to-dentin bond strengths. Immersion in 10 percent
      formalin might be the best option for storage and sterilization of bovine teeth
      that are to be used in dental bonding studies in vitro.

PMID- 18056106
TI  - When and how to repair a failing restoration.

PMID- 18056107
TI  - Keep it simple: reduce unnecessary inventory.

PMID- 18056108
TI  - Can a state society refuse a transfer of a member in good standing?

PMID- 18056109
TI  - Hypothesis: grandiosity and guilt cause paranoia; paranoid schizophrenia is a
      psychotic mood disorder; a review.
AB  - Delusional paranoia has been associated with severe mental illness for over a
      century. Kraepelin introduced a disorder called "paranoid depression," but
      "paranoid" became linked to schizophrenia, not to mood disorders. Paranoid
      remains the most common subtype of schizophrenia, but some of these cases, as
      Kraepelin initially implied, may be unrecognized psychotic mood disorders, so the
      relationship of paranoid schizophrenia to psychotic bipolar disorder warrants
      reevaluation. To address whether paranoia associates more with schizophrenia or
      mood disorders, a selected literature is reviewed and 11 cases are summarized.
      Comparative clinical and recent molecular genetic data find phenotypic and
      genotypic commonalities between patients diagnosed with schizophrenia and
      psychotic bipolar disorder lending support to the idea that paranoid
      schizophrenia could be the same disorder as psychotic bipolar disorder. A
      selected clinical literature finds no symptom, course, or characteristic
      traditionally considered diagnostic of schizophrenia that cannot be accounted for
      by psychotic bipolar disorder patients. For example, it is hypothesized here that
      2 common mood-based symptoms, grandiosity and guilt, may underlie functional
      paranoia. Mania explains paranoia when there are grandiose delusions that one's
      possessions are so valuable that others will kill for them. Similarly, depression
      explains paranoia when delusional guilt convinces patients that they deserve
      punishment. In both cases, fear becomes the overwhelming emotion but patient and
      physician focus on the paranoia rather than on underlying mood symptoms can cause
      misdiagnoses. This study uses a clinical, case-based, hypothesis generation
      approach that warrants follow-up with a larger representative sample of psychotic
      patients followed prospectively to determine the degree to which the clinical
      course observed herein is typical of all such patients. Differential diagnoses,
      nomenclature, and treatment implications are discussed because bipolar patients
      misdiagnosed with schizophrenia are severely misserved.

PMID- 18056110
TI  - Can antistigma campaigns be improved? A test of the impact of biogenetic vs
      psychosocial causal explanations on implicit and explicit attitudes to
      schizophrenia.
AB  - Antistigma campaigns have been promoting a medical view of schizophrenia. Given
      the growing body of research finding negative associations between biogenetic
      (BG) causal attributions and stigmatizing attitudes, this approach must be
      reappraised. The present study investigates the impact of different
      psychoeducational interventions on the etiology of schizophrenia (BG and
      psychosocial [PS], vs a neutral condition) and on stigmatizing attitudes in
      medical (n = 60) and psychology students (n = 61). Information was presented via
      information brochures and a video presentation. Attitudes were assessed before
      and after the interventions on an explicit level using the stereotype
      questionnaire and the Social Distance Scale as well as on an implicit level,
      using the Implicit Association Test. Both educational interventions produced a
      significant decrease in several stereotype components, which was not the case in
      the neutral condition. The BG intervention decreased the attribution of blame in
      both groups. It also decreased the stereotype unpredictability/incompetence and
      social distance in the medical students but increased the negative outlook on
      prognosis in the psychology students. The PS intervention reduced the widespread
      stereotype of dangerousness as well as social distance in the group of medical
      students. While further research into antistigma interventions is necessary, the
      proposal for antistigma campaigns is to take a multidimensional and balanced
      approach, which is adapted to target groups and provides additional facts that
      challenge the myths maintaining stigma.

PMID- 18056111
TI  - Back to basals: do basal dendrites link plateau potentials and Up states?

PMID- 18056112
TI  - Reshaping the binding problem of form and motion vision.

PMID- 18056113
TI  - Understanding the role of voltage gating of polymodal TRP channels.

PMID- 18056114
TI  - Inhibition facilitates depression.

PMID- 18056115
TI  - Bayesian modeling of embryonic growth using latent variables.
AB  - In a growth model, individuals move progressively through a series of states in
      which each state is indicative of developmental status. Interest lies in
      estimating the rate of progression through each state while incorporating
      covariates that might affect the transition rates. We develop a Bayesian discrete
      time multistate growth model for inference from cross-sectional data with unknown
      initiation times. For each subject, data are collected at only one time point at
      which we observe the state as well as covariates that measure developmental
      progress. We link the developmental progress variables to an underlying latent
      growth variable that can also affect the state transition rates. A subject with
      slow latent growth will then have relatively small developmental progress
      covariates and move through state transitions slowly. We then examine the
      association between latent growth and the probability of future events in a novel
      study of embryonic development and pregnancy loss. Using a Markov chain Monte
      Carlo (MCMC) algorithm for posterior computation, we found evidence in favor of a
      previously hypothesized but unproven association between slow growth early in
      pregnancy and increased risk of future spontaneous abortion.

PMID- 18056116
TI  - Aldo-keto reductase family 1 B10 affects fatty acid synthesis by regulating the
      stability of acetyl-CoA carboxylase-alpha in breast cancer cells.
AB  - Recent studies have demonstrated that aldo-keto reductase family 1 B10 (AKR1B10),
      a novel protein overexpressed in human hepatocellular carcinoma and non-small
      cell lung carcinoma, may facilitate cancer cell growth by detoxifying
      intracellular reactive carbonyls. This study presents a novel function of AKR1B10
      in tumorigenic mammary epithelial cells (RAO-3), regulating fatty acid synthesis.
      In RAO-3 cells, Sephacryl-S 300 gel filtration and DEAE-Sepharose ion exchange
      chromatography demonstrated that AKR1B10 exists in two distinct forms, monomers
      (approximately 40 kDa) bound to DEAE-Sepharose column and protein complexes
      (approximately 300 kDa) remaining in flow-through. Co-immunoprecipitation with
      AKR1B10 antibody and protein mass spectrometry analysis identified that AKR1B10
      associates with acetyl-CoA carboxylase-alpha (ACCA), a rate-limiting enzyme of de
      novo fatty acid synthesis. This association between AKR1B10 and ACCA proteins was
      further confirmed by co-immunoprecipitation with ACCA antibody and pulldown
      assays with recombinant AKR1B10 protein. Intracellular fluorescent studies showed
      that AKR1B10 and ACCA proteins co-localize in the cytoplasm of RAO-3 cells. More
      interestingly, small interfering RNA-mediated AKR1B10 knock down increased ACCA
      degradation through ubiquitination-proteasome pathway and resulted in >50%
      decrease of fatty acid synthesis in RAO-3 cells. These data suggest that AKR1B10
      is a novel regulator of the biosynthesis of fatty acid, an essential component of
      the cell membrane, in breast cancer cells.

PMID- 18056117
TI  - Optimal perfusion of an intact ovary as a prerequisite for successful ovarian
      cryopreservation.
AB  - BACKGROUND: Cryopreservation and subsequent reimplantation of intact ovaries from
      cancer patients, offers potentially the best prognosis for restoring fertility
      after sterilizing cancer treatment. We used bovine ovaries as a model system to
      explore the perfusion procedure that is required for cryopreservation of intact
      ovaries. METHODS: The arteria ovarica was cannuled, and ovaries were flushed with
      Indian ink for 5 min. RESULTS: Successful perfusion of blood vessels was
      immediately visible macroscopically by a grey to black discoloration of the ovary
      and was confirmed microscopically, by examining tissue sections. There was no
      correlation between the time interval from removal of the ovary to the start of
      the perfusion, and success of perfusion. We determined the percentage of Indian
      ink-perfused vessels and scored blood vessels in four different size classes. The
      percentage of perfused vessels increased with an increase in vessel size. In a
      limited set of preliminary experiments with human ovaries, comparable results
      were obtained. CONCLUSIONS: Our results show that bovine ovaries are a suitable
      and adequate model system for optimizing the cryopreservation of human ovaries.
      As bovine are at least of comparable size to human ovaries, we expect that our
      results can be extrapolated to the human situation.

PMID- 18056118
TI  - Cryopreservation of ovarian tissue and in vitro matured oocytes in a female with
      mosaic Turner syndrome: Case Report.
AB  - We report a novel approach of fertility preservation in a young woman with mosaic
      Turner syndrome. A 16-year-old female with 20% 45XO and 80% 46XX karyotype
      underwent laparoscopic ovarian wedge resection. Before performing ovarian tissue
      cryopreservation, all visible follicles on the ovarian surface were aspirated. We
      recovered 11 immature germinal vesicle stage oocytes, which were subjected to in
      vitro maturation (IVM). Eight oocytes that matured (73% maturation rate) were
      cryopreserved by vitrification. The combination of ovarian tissue cryobanking and
      immature oocyte collection from the tissue followed by IVM and vitrification of
      matured oocytes represent a promising approach of fertility preservation for
      young women with mosaic Turner syndrome.

PMID- 18056119
TI  - Inhibition of steroid sulphatase activity in endometriotic implants by 667
      COUMATE: a potential new therapy.
AB  - BACKGROUND: Local biosynthesis of estrogens is thought to be important for the
      maintenance and growth of endometriotic implants. In addition to the formation of
      estrogen via the aromatase pathway, steroid sulphatase (STS), which is
      responsible for the hydrolysis of estrogen sulphates, may be an important source
      of estrogens in endometriosis. METHODS: Eutopic and ectopic endometrial samples
      from 14 women with minimal or mild (MM) endometriosis and from 13 women with
      moderate to severe (MS) endometriosis were analysed for aromatase and STS
      activities. RESULTS: Aromatase and STS activity were detected in all samples. STS
      enzyme activity in both eutopic and ectopic endometrium was considerably higher
      and less variable than aromatase activity. Moreover, STS, but not aromatase,
      activity in endometriotic implants correlated with the severity of the disease
      (mean +/- SEM: 203 +/- 38 nmol/4 h/g wet weight tissue in MM disease versus 423
      +/- 44 nmol/4 h/g wet weight tissue in MS endometriosis, P < 0.001). The STS
      inhibitor 667 COUMATE almost completely blocked STS activity (>99%) in both
      eutopic and ectopic tissues. CONCLUSIONS: The high levels of STS activity
      detected in ectopic endometrium and the correlation with severity of disease
      suggest that STS inhibitors could be useful for the treatment of endometriosis.

PMID- 18056120
TI  - When do social inequalities in C-reactive protein start? A life course
      perspective from conception to adulthood in the Cardiovascular Risk in Young
      Finns Study.
AB  - BACKGROUND: It is unclear when in the life course do social inequalities in
      inflammation emerge. We examined whether the association between socioeconomic
      position (SEP) and C-reactive protein (CRP) is determined at conception, in
      childhood, adolescence or adulthood in 1484 participants from the population
      based Cardiovascular Risk in Young Finns Study. METHODS: Five variants of the CRP
      gene were used to investigate whether SEP differences in CRP levels are
      determined at conception. SEP and serum CRP were assessed in childhood (age 3-9),
      adolescence (age 12-18) and in adulthood (age 24-39). SEP was measured using
      parental education and occupational status in childhood and adolescence, and
      participants' own education and occupational status in adulthood. Participants
      with CRP > 10 mg/l were excluded. RESULTS: All CRP gene variants were associated
      with circulating CRP concentrations in childhood, but there were no differences
      in the distribution of these variants by SEP. No strong evidence was found of
      associations between parental SEP and CRP. A graded association between higher
      SEP and lower CRP was observed in adulthood for education (P = 0.0005) but not
      for occupational status. Trajectories that led to high educational achievement
      both in the participants and their parents were associated with lower (P <or=
      0.047) CRP levels in adulthood. Excluding participants with infectious diseases,
      pregnant or lactating women and women using oral contraceptives did not change
      the findings. CONCLUSION: In this cohort, SEP differences in CRP concentrations
      seen in adulthood appear not to be determined at conception or evident in
      childhood or adolescence.

PMID- 18056121
TI  - An exploratory method for estimating the changing speed of epidemic waves from
      historical data.
AB  - BACKGROUND: Historical data are necessary to establish long-term trends in
      disease incidence but pose analytical problems since their accuracy and
      reliability may be poorly specified. METHODS: A robust measure of the spatial
      velocity, R(0A), of epidemic waves from space-time series is proposed using
      binary data. The method was applied to the historical records of influenza
      morbidity for the island of Iceland over a 61-year period of influenza seasons
      from 1915-16 to 1975-76. RESULTS: The onset of influenza waves tended to speed up
      over the period studied and the three pandemic waves associated with viral shifts
      in influenza A [Spanish influenza H1N1 (1918-19), Asian influenza H2N2 (1957-58)
      and Hong Kong influenza H3N2 (1968-69)] spread more rapidly around the island and
      struck earlier in the influenza season than did inter-pandemic waves, even when
      the latter were equally intensive as measured by total number of cases and case
      incidence. DISCUSSION: The potential for using R(0A) in a real-time context is
      explored using French influenza data. CONCLUSIONS: The new measure of wave
      velocity appears to be applicable to those historical time series where breakdown
      into regional or local areas is available. The study is being extended to (i)
      other countries where similar influenza time series are available and (ii) to
      other diseases within Iceland.

PMID- 18056123
TI  - Self-rated health: caught in the crossfire of the quest for 'true' health?

PMID- 18056122
TI  - Parental smoking and childhood obesity--is maternal smoking in pregnancy the
      critical exposure?
AB  - BACKGROUND: The concept of priming of childhood obesity by prenatal exposure to
      maternal smoking is based on a number of consistent studies. A recent paper found
      similar associations between paternal smoking and childhood obesity, questioning
      the presumed causal effect attributed to the prenatal exposure. Is the relation
      to paternal smoking consistent? Does it explain the effect of maternal smoking
      before or in pregnancy? METHODS: Data from a cross sectional study on 5899
      children in the setting of the 2005 school entrance health examinations in
      Bavaria were analysed. Associations between paternal smoking or maternal smoking
      before or in pregnancy and childhood obesity were assessed with adjustment for
      potential confounders. RESULTS: The children's mean age was 5.8 years. The
      unadjusted odds ratio for obesity and paternal smoking was 2.0 (95% CI: 1.5, 2.6)
      and similar to that for maternal smoking before or in pregnancy with 2.3 (95% CI:
      1.8, 3.1). After adjustment for a number of potential confounders and paternal
      smoking at interview the odds ratio for maternal smoking before or in pregnancy
      and childhood obesity was 1.9 (95% CI: 1.3, 2.7). There was no evidence for
      interaction between paternal smoking and maternal smoking before or in pregnancy
      (P = 0.38). CONCLUSIONS: Although of similar magnitude, the association of
      paternal smoking could only partially explain the effect of maternal smoking
      before or in pregnancy on childhood obesity. Whether this persistent association
      reflects residual confounding or causality is unclear.

PMID- 18056124
TI  - Uses of epidemiology. 1955.

PMID- 18056125
TI  - Commentary: ways of asking and ways of living: reflections on the 50th
      anniversary of Morris' ever-useful Uses of Epidemiology.

PMID- 18056126
TI  - Calculating health and social change: an essay on Jerry Morris and Late-modernist
      epidemiology.

PMID- 18056127
TI  - Fifty years of JN Morris's Uses of Epidemiology.

PMID- 18056128
TI  - Commentary: need to role out brief interventions in primary care settings to
      address problem drinking while expanding research in developing and transitional
      countries.

PMID- 18056129
TI  - Commentary: migration and health--what about those who stay at home?

PMID- 18056130
TI  - Commentary: defining a minimum income for healthy living (MIHL): older age,
      England--a comment on implications for application in the developing world.

PMID- 18056131
TI  - Association of diarrhoea in childhood with blood pressure and coronary heart
      disease in older age: analyses of two UK cohort studies.
AB  - BACKGROUND: There is a suggestion that acute dehydration in childhood may lead to
      elevated blood pressure. We examined if episodes of diarrhoea in childhood, a
      recognized proxy for acute dehydration, were related to measured blood pressure
      and coronary heart disease in older adults. METHODS: Data were pooled from two
      prospective UK cohort studies (participants born 1920-39) in which episodes of
      diarrhoea were ascertained from health visitor records from birth until 5 years
      of age. Blood pressure and coronary heart disease were assessed during medical
      examination in men and women over 64 years of age. In total, 5203 men and women
      had data on diarrhoea in early life, adult blood pressure and a range of
      covariates; 4181 of these also had data on coronary heart disease status.
      RESULTS: The prevalence of diarrhoea in infancy (3.3%) and between 1 and 5 years
      (1.1%) was low. There was no relation of diarrhoea from either period (age- and
      sex-adjusted results for diarrhoea in infancy presented here) with measured blood
      pressure [coefficient for systolic; 95% CI (confidence interval): 0.44; -2.88
      3.76] or coronary heart disease (Odds ratio, OR; 95% CI: 0.91; 0.54-1.54) in
      adulthood. There was a similar lack of association when hypertension was the
      outcome of interest. These observations were unchanged after adjustment for a
      range of covariates. CONCLUSIONS: In the largest study to date to examine the
      relation, there was no evidence that diarrhoea in early life had an influence on
      measured blood pressure, hypertension or coronary heart disease in older adults.

PMID- 18056132
TI  - Automation of in-silico data analysis processes through workflow management
      systems.
AB  - Data integration is needed in order to cope with the huge amounts of biological
      information now available and to perform data mining effectively. Current data
      integration systems have strict limitations, mainly due to the number of
      resources, their size and frequency of updates, their heterogeneity and
      distribution on the Internet. Integration must therefore be achieved by accessing
      network services through flexible and extensible data integration and analysis
      network tools. EXtensible Markup Language (XML), Web Services and Workflow
      Management Systems (WMS) can support the creation and deployment of such systems.
      Many XML languages and Web Services for bioinformatics have already been designed
      and implemented and some WMS have been proposed. In this article, we review a
      methodology for data integration in biomedical research that is based on these
      technologies. We also briefly describe some of the available WMS and discuss the
      current limitations of this methodology and the ways in which they can be
      overcome.

PMID- 18056133
TI  - Dealing with uncertainties: ethics of prenatal diagnosis and preimplantation
      genetic diagnosis to prevent mitochondrial disorders.
AB  - This paper aims to address the ethical issues regarding prenatal diagnosis and
      preimplantation genetic diagnosis (PGD) of mitochondrial disorders. Owing to the
      absence of effective treatment, the prevention of the transmission of
      mitochondrial disorders is considered to be of key importance. The
      characteristics of mtDNA, such as heteroplasmy and the genetic bottleneck, make
      it difficult to estimate recurrence risks correctly and to provide an accurate
      prognosis for many mtDNA mutations. A limited number of mtDNA mutations allow
      reliable predictions, though results in the 'grey zone' are problematic. Both
      prenatal diagnosis and PGD for mtDNA disorders are complicated by the
      interpretation of the test results. As a consequence, these applications confront
      both clinical practice and society at large with several ethical questions and
      issues for further debate, among which the acceptability of suboptimal genetic
      testing, the value and research use of embryos, the evaluation of late abortion,
      the ethics of PGD for disorders with an incomplete penetrance and variable
      expression, the possible transfer of embryos with residual health risks, the
      acceptability of risks and drawbacks of genetic reproductive technology in
      general, and the scope and limits of reproductive autonomy and professional
      responsibility.

PMID- 18056134
TI  - Identification of the right middle pulmonary vein ostium by translucent three
      dimensional image of multi-detector computed tomography.

PMID- 18056135
TI  - Baseline Doppler parameters are useful predictors of chronic left ventricular
      reduction in size by cardiac resynchronization therapy.
AB  - AIMS: The identification of responders to cardiac resynchronization therapy (CRT)
      in patients with left ventricular (LV) dysfunction and left bundle branch block
      (LBBB) remains difficult. We aimed to define the predictive value of conventional
      Doppler parameters. METHODS AND RESULTS: In 73 patients (65 +/- 9 years, 51 male,
      36 ischaemic, 37 non-ischaemic cardiomyopathy, QRS 167 +/- 31 ms, LVEF 23 +/- 6%)
      with LBBB, a CRT device was implanted. LV pre-ejection interval (PEI),
      interventricular mechanical delay (IVMD), LV filling time (FT), and myocardial
      performance index (MPI) were assessed at baseline and on optimized CRT. Left
      ventricular end-diastolic diameter (EDD) was obtained at baseline and after 10.6
      +/- 6.7 months. end-diastolic diameter diminished from 66.3 +/- 8.1 to 59.9 +/-
      9.6 mm (P < 0.001). Initial LVPEI (r = 0.41, P < 0.001), baseline IVMD (r = 0.34,
      P = 0.003), acute LVPEI shortening (r = 0.33, P = 0.006), and baseline LVEDD (r =
      0.32, P = 0.007) correlated with LVEDD reduction. An LVPEI > or =140 ms had a 82%
      accuracy to predict long-term LVEDD reduction (sensitivity 86%, specificity 67%,
      positive and negative predictive values 91 and 56%, respectively). Multivariate
      analysis solely revealed baseline LVPEI as predictor of LVEDD reduction. FT and
      MPI correlated only with their respective improvements. CONCLUSION: Left
      ventricular pre-ejection interval and IVMD predict favourable LV remodelling on
      CRT. The additional application of tissue Doppler parameters may further increase
      specificity and negative predictive value.

PMID- 18056137
TI  - Effects of heart failure on brain-type Na+ channels in rabbit ventricular
      myocytes.

PMID- 18056138
TI  - The temporal relationships between sleep, cortisol, and lung functioning in youth
      with asthma.
AB  - OBJECTIVES: This study tested the directionality of the association between sleep
      and health outcomes in youth with asthma. METHOD: Thirty-eight youth with asthma
      (aged 9-19) completed a daily diary study on sleep, asthma symptoms, peak
      expiratory flow (PEF) measures, and salivary cortisol samples. RESULTS: Greater
      quantity of sleep predicted lower PEF% [beta(32) = -.33, p =.02], and lower daily
      cortisol output [beta(33) = -.31, p =.07] the following day. Additionally, poorer
      self-reported sleep quality predicted more severe symptoms the next day [beta(33)
      =.27, p =.05]. In contrast, PEF%, cortisol, and asthma symptoms did not
      significantly predict self-reported sleep quantity or quality the next night.
      CONCLUSIONS: Results suggest that sleep may affect subsequent health outcomes,
      rather than asthma impacting subsequent sleep, indicating the potential benefits
      of targeting sleep behaviors in youth with asthma.

PMID- 18056139
TI  - Actigraphic sleep and daytime naps in adolescent girls with chronic
      musculoskeletal pain.
AB  - OBJECTIVES: A descriptive pilot study to examine sleep and daytime naps in
      adolescent girls with chronic musculoskeletal (MSK) pain. METHODS: Seventeen
      girls (14.9 +/- 2.0 years) completed questionnaires on anxiety and depressive
      symptoms during their clinic visit, and maintained a sleep diary and wore an
      actigraph for 7 days. Parents completed a daily diary of their teen's medications
      and approaches used to ease pain. RESULTS: Average nighttime sleep was 7.2 hr by
      actigraphy. All participants had mean sleep efficiency <90%. In diaries, 76.5% of
      the girls reported daytime naps; five girls reported more than three days with
      naps and more naps were associated with lower sleep efficiency and total
      nighttime sleep. CONCLUSIONS: Adolescent girls with chronic MSK pain may sleep
      fewer hours at night than is recommended and nap in the daytime to compensate for
      insufficient nighttime sleep.

PMID- 18056140
TI  - Caregiver stress and outcomes of children with pediatric feeding disorders
      treated in an intensive interdisciplinary program.
AB  - OBJECTIVE: This study investigated the impact of an intensive interdisciplinary
      feeding program on caregiver stress and child outcomes of children with feeding
      disorders across three categories. METHODS: Children were categorized into either
      tube dependent, liquid dependent, or food selective groups. Outcomes for
      caregiver stress levels, child mealtime behaviors, weight, and calories were
      examined at admission and discharge for 121 children. Repeated measures ANOVAs
      were used to examine differences pre- and post-treatment and across feeding
      categories. RESULTS: Caregiver stress, child mealtime behaviors, weight, and
      caloric intake improved significantly following treatment in the intensive
      feeding program, regardless of category placement. CONCLUSIONS: Few studies have
      examined the impact of an intensive interdisciplinary approach on caregiver
      stress, as well as on child outcome variables with such a diverse population.
      This study provides support that regardless of a child's medical and feeding
      history, an intensive interdisciplinary approach significantly improves caregiver
      stress and child outcomes.

PMID- 18056142
TI  - A developmental perspective on functional somatic symptoms.
AB  - OBJECTIVE: To provide a new approach for conceptualizing and studying functional
      somatic symptoms (FSS) in children and adolescence. METHODS: A developmental
      model is proposed based on the synthesis of the extant literature and previous
      theoretical perspectives of FSS in children and adolescents. RESULTS: Multiple
      risk and protective factors from child, familial, social, and environmental
      domains, the interactions across risk domains, and potential developmental
      pathways of FSS are identified. CONCLUSIONS: This article underscores the
      necessity of taking a broader, developmental view of FSS. The tenets of
      developmental psychopathology emphasize the utility of viewing FSS on a continuum
      of severity rather than as a discrete entity or diagnosis. This article concludes
      with directions for future research and treatment implications.

PMID- 18056143
TI  - Developing smoking cessation programs for chronically ill teens: lessons learned
      from research with healthy adolescent smokers.
AB  - OBJECTIVE: Medically fragile teens who smoke need access to smoking cessation
      programs, because they are at even higher risk than their healthy peers for
      smoking-related complications. METHODS: To date, no studies on the outcome of
      smoking cessation programs for medically ill teens have been conducted. To
      suggest directions for future research, we turn to the literature on smoking
      cessation in the general population of teens and occasionally to the literature
      on adult smokers. RESULTS: Four areas are explored: (a) the prevalence of unaided
      cessation in healthy teens; (b) the outcomes of various treatments for smoking
      cessation in healthy adolescents; (c) special issues that should be considered
      when designing programs for medically ill teens; and (d) lessons learned from
      previous research. CONCLUSIONS: Medically ill teens face a number of medical,
      emotional, social, and developmental challenges that can affect the quitting
      process. Research is sorely needed to address the unique needs of this
      population.

PMID- 18056145
TI  - Psychosocial adjustment, health-related quality of life, and psychosexual
      development of boys with hypospadias: a systematic review.
AB  - OBJECTIVE: A systematic review of studies on psychosocial adjustment, HRQoL
      (health-related quality of life), and psychosexual development of boys with
      hypospadias. METHODS: Research was conducted on several online bibliographic
      databases. Articles were selected on the basis of predefined criteria.
      Methodological quality was assessed by two independent reviewers who applied a
      standardized checklist. When possible, data analyses were performed by
      calculating effect sizes. RESULTS: Thirteen studies met the criteria for
      inclusion, whose methodological standard ranged from low to high quality. None of
      them has focused on HRQoL. Findings with regard to psychosocial and psychosexual
      adjustment were inconsistent, though they clearly showed that boys with
      hypospadias suffer from negative genital appraisal and sexual inhibitions.
      Overall, medical factors exerted a rather small influence. Psychosocial risk
      factors have hardly been examined so far. CONCLUSIONS: The identification of
      psychosocial risk factors in methodologically sound studies is necessary to
      guarantee a comprehensive treatment for boys with hypospadias.

PMID- 18056144
TI  - Acute impact of immediate release methylphenidate administered three times a day
      on sleep in children with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To determine the impact of immediate release Ritalin, given three
      times a day, on sleep quality and quantity in medication-naive, newly diagnosed
      children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Children
      (aged 6-12) rigorously diagnosed with ADHD (n = 21) underwent multiple
      measurement assessments (i.e., actigraphy, sleep diary, and questionnaires)
      during a 1-week baseline and then during a 3-week blinded randomized medication
      trial. RESULTS: Although the medication was effective in reducing ADHD symptoms,
      analyses of actigraphy and sleep diary data found statistically and clinically
      significant changes in the children's total sleep time and sleep onset latency in
      the medication compared to the no medication conditions. No effects on sleep were
      found based on the sleep questionnaire. CONCLUSIONS: Physicians and parents are
      encouraged to closely monitor children's sleep when treating ADHD with stimulant
      medication.

PMID- 18056146
TI  - Use of parenteral methotrexate significantly reduces the need for biological
      therapy.

PMID- 18056147
TI  - Comment on: Do baseline characteristics predict response to treatment for low
      back pain? Secondary analysis of the UK BEAM dataset.

PMID- 18056148
TI  - Comment on: A prospective double-blind placebo-controlled randomized trial of
      ultrasound in the physiotherapy treatment of shoulder pain.

PMID- 18056149
TI  - Infliximab therapy reduces periodontoid rheumatoid pannus formation.

PMID- 18056150
TI  - Comment on: Failure of anti-TNF therapy in TNF receptor 1-associated periodic
      syndrome (TRAPS).

PMID- 18056151
TI  - Transcranial Doppler and acoustic pressure fluctuations for the assessment of
      cavitation and thromboembolism in patients with mechanical heart valves.
AB  - The formation and collapse of vapor-filled bubbles near a mechanical heart valve
      is called cavitation. Such microbubbles are suspected to have strong pro
      coagulant effects. Therefore, cavitation may be a contributing factor to the pro
      thrombotic effects of mechanical valves. Herein, we systematically review the
      available evidence linking cavitation and thrombosis. We also critically appraise
      the potential usefulness of transcranial Doppler and other new non-invasive
      diagnostic methods to study cavitation and cerebral embolism in mechanical valve
      patients. Experimental studies indicate that cavitation microbubbles cause
      platelet aggregation, complement-activation, fibrinolysis, release of tissue
      factor, and endothelial damage. Administration of 100% oxygen to mechanical valve
      patients during transcranial Doppler examination can transiently decrease the
      counts of Doppler-detected cerebral microemboli compared with room air. This is
      associated with removal of most circulating gaseous emboli from cavitation. This
      method may therefore be applied to the study of cavitation and thromboembolism.
      Additionally, the analysis of high-frequency acoustic-pressure fluctuations
      detected from the implosion of cavitation bubbles is a promising method for
      assessment of cavitation in vivo; however, this requires further development. A
      better understanding of cavitation is important in order to adequately
      investigate its role in the overall pro-thrombotic effects in mechanical valve
      patients. Such studies may allow establishing guidelines for new valve designs.

PMID- 18056152
TI  - Heparin induced thrombocytopenia diagnosis in cardiac surgery: is there a role
      for thromboelastography?
AB  - The aim of the present protocol is to investigate the potency of
      thromboelastography (TEG) to screen postcardiac heparin induced thrombocytopenia
      (HIT) patients suspicious for HIT type II, and to differentiate which of them are
      subject to suffer thrombotic complications from those who will suffer hemorrhagic
      complications.

PMID- 18056153
TI  - Novel adjunct to surgery for end-stage cardiomyopathy receiving hemodialysis.
AB  - Surgical management of heart failure patients receiving hemodialysis (HD) is a
      challenge to surgeons and reports are limited. Five patients receiving HD
      underwent a mitral annuloplasty with or without restoration of the left ventricle
      because of class III or IV heart failure due to mitral regurgitation and poor
      ventricular functions. Of those, three fully recovered to NYHA class I after the
      cardiac procedure, however, two patients remained symptomatic and required an
      adjunctive procedure. For that, we converted the arteriovenous dialysis shunt to
      an inter-arterial bypass by dividing the venous side of the shunt and
      anastomosing it to the proximal radial artery (RA), followed by ligation of the
      RA between the two anastomoses so that the RA was bypassed by the cephalic vein.
      Following this procedure, left ventricular end-diastolic pressure and volume were
      reduced, and heart failure symptoms diminished. This simple procedure was able to
      reduce the cardiac overload, while keeping the vascular access intact and may be
      a relevant adjunct to surgical reverse remodeling in end-stage heart failure
      patients receiving HD.

PMID- 18056154
TI  - The influence of levosimendan and iloprost on renal ischemia-reperfusion: an
      experimental study.
AB  - The effects of iloprost on ischemia-reperfusion injury have been studied on the
      skeletal, muscle, liver, myocardium, kidney, and spinal cord. However, no
      sufficient data exist about effects of levosimendan on renal ischemia-reperfusion
      injury. The purpose of this experimental study was to investigate and compare
      effectiveness of levosimendan and iloprost on renal injury induced by ischemia
      and reperfusion. Fifty rabbits were divided into five groups. Levosimendan was
      continuously infused starting half an hour before the cross-clamp. Cross-clamp
      time was one hour. After one hour ischemia, levosimendan was continued for 4 h in
      Group A whereas Group B took iloprost in the same protocol. Group C was the
      control group which did not receive any medication. Group D was sham group and
      Group E was medicated both iloprost and levosimendan. Renal tissues were
      histologically and biochemically evaluated. The histological scores were obtained
      according to presence of tubular necrosis and atrophy, regenerative atypia,
      hydropic degeneration (Group A vs. Group C<0.001, Group B vs. Group C<0.001,
      Group D vs. Group C<0.01, Group E vs. Group C<0.001). Mean malondialdehyde levels
      were 114+/-12 nmol/g tissue; in Group A 121+/-13 nmol/g tissue, in Group B 134+/
      13 nmol/g tissue, in Group E 130+/-11 nmol/g tissue, in Group D 134+/-11 nmol/g
      tissue (Group A vs. Group B; P=0.003, Group B vs. Group D; P=0.132, Group A vs.
      Group E; P=0.132). Malondialdehyde levels and histologic scores of all of the
      groups were significantly different from the control group. Iloprost and
      pentoxyfillin reduced renal ischemia-reperfusion injury in rabbit model. There
      was no significant difference between these two medications.

PMID- 18056155
TI  - Comprehensive association testing of common genetic variation in DNA repair
      pathway genes in relationship with breast cancer risk in multiple populations.
AB  - Genetic association studies of multiple populations investigate a wider range of
      risk alleles than studies of a single ethnic group. In this study, we developed a
      multiethnic tagging strategy, exploiting differences in linkage disequilibrium
      (LD) structure between populations, to comprehensively capture common genetic
      variation across 60 genes spanning multiple DNA repair pathways, in five
      racial/ethnic populations. Over 2600 SNPs were genotyped in each population and
      single- and multi-marker predictors of common alleles were selected to capture
      the LD patterns specific to each group. Coding variants (n = 211) were genotyped
      to test whether combinations of putative functional variants in DNA repair
      pathway genes could have cumulative effects on risk. Tests of association were
      conducted in a multiethnic breast cancer study (2093 cases and 2303 controls),
      with validation of the top allelic associations (P </= 0.01) performed in
      additional studies of 6483 cases and 7309 controls. A variant in the FANCA gene
      (rs1061646, 0.15-0.68 frequency across populations) was associated with risk in
      the initial study (P = 0.0052), and in the replication studies (P = 0.032). In a
      combined analysis (8556 cases and 9605 controls), this SNP yielded an 8% increase
      in risk per allele. Combinations of coding variants in these genes were not
      associated with breast cancer and together, these data suggest that common
      variation in these DNA repair pathway genes are not strongly associated with
      breast cancer risk. The methods utilized in this study, applied to multiple
      populations, provide a framework for testing in association studies in diverse
      populations.

PMID- 18056156
TI  - Enzyme replacement therapy in a murine model of Morquio A syndrome.
AB  - Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by
      a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to
      accumulation of keratan sulfate (KS) and chrondroitin-6-sulfate. The
      pharmacokinetics and biodistributions were determined for two recombinant human
      GALNSs produced in CHO cell lines: native GALNS and sulfatase-modifier-factor 1
      (SUMF1) modified GALNS. Preclinical studies of enzyme replacement therapy (ERT)
      by using two GALNS enzymes were performed on MPS IVA mice. The half-lives in
      blood circulation of two phosphorylated GALNS enzymes were similar (native, 2.4
      min; SUMF1, 3.3 min). After intravenous doses of 250 units/g body weight were
      administered, each enzyme was primarily recovered in liver and spleen, with
      detectable activity in other tissues including bone and bone marrow. At 4 h post
      injection, enzyme activity was retained in the liver, spleen, bone and bone
      marrow at levels that were 20-850% of enzyme activity in the wild-type mice.
      After intravenous doses of 250 units/g of native GALNS, and 250, 600 or 1000
      units/g of SUMF1-GALNS were administered weekly for 12 weeks, MPS IVA mice showed
      marked reduction of storage in visceral organs, sinus lining cells in bone
      marrow, heart valves, ligaments and connective tissues. A dose-dependent
      clearance of storage material was observed in brain. The blood KS level assayed
      by tandem mass spectrometry was reduced nearly to normal level. These preclinical
      studies demonstrate the clearance of tissue and blood KS by administered GALNS,
      providing the in vivo rationale for the design of ERT trials in MPS IVA.

PMID- 18056158
TI  - Grey and white matter distribution in very preterm adolescents mediates
      neurodevelopmental outcome.
AB  - Very preterm (VPT) birth is associated with altered cortical development and long
      term neurodevelopmental sequelae. We used voxel-based morphometry to investigate
      white (WM) and grey matter (GM) distribution in VPT adolescents and controls, and
      the association with gestational age and neonatal ultrasound findings in the VPT
      individuals. GM and WM volumes were additionally investigated in relation to
      adolescent neurodevelopmental outcome. Structural MRI data were acquired with a
      1.5 Tesla machine in 218 VPT adolescents (<33 weeks, gestation) and 128 controls
      aged 14-15 years, and analysed using SPM2 software. VPT individuals compared to
      controls showed reduced GM in temporal, frontal, occipital cortices and
      cerebellum, including putamen, insula, cuneus, fusiform gyrus, thalamus and
      caudate nucleus, and increased GM predominantly in temporal and frontal lobes,
      including cingulate and fusiform gyri and cerebellum. WM loss was concentrated in
      the brainstem, internal capsule, temporal and frontal regions and the major
      fasciculi. WM excesses were observed in temporal, parietal and frontal regions.
      Investigation of the inter-relationships between brain regions and changes
      revealed that all selected areas where between-group increased and decreased WM
      and GM volumes differences were observed, were structurally associated,
      highlighting the influence that abnormalities in one brain area may exert over
      others. VPT individuals with evidence of periventricular haemorrhage and
      ventricular dilatation on neonatal ultrasound exhibited the greatest WM and GM
      alterations. VPT adolescents obtained lower scores than controls on measures of
      language and executive function and were more likely to show cognitive impairment
      compared to controls (27% versus 14%, respectively). Several areas where VPT
      individuals demonstrated decreased GM and WM volume were linearly associated with
      gestational age and mediated cognitive impairment. To summarize, our data
      demonstrates that VPT birth is associated with altered brain structure in
      adolescence. GM and WM alterations are associated with length of gestation and
      mediate adolescent neurodevelopmental impairment. Thus, anatomical brain changes
      may contribute to specific cognitive deficits associated with VPT birth and could
      be used in the identification of those individuals who may be at increased risk
      for cognitive impairment.

PMID- 18056157
TI  - Escherichia coli low-copy-number plasmid R1 centromere parC forms a U-shaped
      complex with its binding protein ParR.
AB  - The Escherichia coli low-copy-number plasmid R1 contains a segregation machinery
      composed of parC, ParR and parM. The R1 centromere-like site parC contains two
      separate sets of repeats. By atomic force microscopy (AFM) we show here that ParR
      molecules bind to each of the 5-fold repeated iterons separately with the
      intervening sequence unbound by ParR. The two ParR protein complexes on parC do
      not complex with each other. ParR binds with a stoichiometry of about one ParR
      dimer per each single iteron. The measured DNA fragment lengths agreed with B
      form DNA and each of the two parC 5-fold interon DNA stretches adopts a linear
      path in its complex with ParR. However, the overall parC/ParR complex with both
      iteron repeats bound by ParR forms an overall U-shaped structure: the DNA folds
      back on itself nearly completely, including an angle of approximately 150 degrees
      . Analysing linear DNA fragments, we never observed dimerized ParR complexes on
      one parC DNA molecule (intramolecular) nor a dimerization between ParR complexes
      bound to two different parC DNA molecules (intermolecular). This bacterial
      segrosome is compared to other bacterial segregation complexes. We speculate that
      partition complexes might have a similar overall structural organization and, at
      least in part, common functional properties.

PMID- 18056159
TI  - Neural correlates of tic severity and cognitive control in children with Tourette
      syndrome.
AB  - Tourette syndrome (TS) is a neurodevelopmental disorder characterized by
      involuntary motor and phonic tics. It is hypothesized that excess dopamine leads
      to an imbalance in the pathways through the basal ganglia, resulting in unchecked
      movements via thalamic disinhibition. It has been unclear whether TS is
      associated with cognitive control deficits as well as pure motor control
      deficits, or whether cognitive deficits are associated with the presence of
      comorbid conditions. Furthermore, little is known about the neural underpinnings
      of TS in childhood, prior to the long-term effects of medication on brain
      function. Here, children with TS and typically developing children performed a
      cognitive control task during event-related fMRI data acquisition. The study
      included 18 native English-speaking 7-13-year-old children with TS (M = 10.42; 15
      males), and 19 healthy, age-matched native English-speaking volunteers (M =
      10.33; 11 males). The task involved three separate manipulations of cognitive
      control. Behaviourally, higher tic severity was correlated with slower task
      performance on the most demanding task conditions. Neurally, higher tic severity
      was associated with enhanced activation of dopaminergic nuclei (substantia
      nigra/ventral tegmental area) and cortical, striatal and thalamic regions in the
      direct pathway. Heightened tic severity was also associated with greater
      engagement of the subthalamic nucleus area, suggestive of a compensatory
      mechanism. Overall, patients engaged left prefrontal cortex more strongly than
      typicals during task performance. These data suggest that children aged 7-13
      unmedicated for TS exhibit increased activation in the direct pathway through the
      basal ganglia, as well as increased compensatory activation in prefrontal cortex
      and the subthalamic nucleus.

PMID- 18056160
TI  - Changes in readthrough acetylcholinesterase expression modulate amyloid-beta
      pathology.
AB  - Alzheimer's disease has long been known to involve cholinergic deficits, but the
      linkage between cholinergic gene expression and the Alzheimer's disease amyloid
      pathology has remained incompletely understood. One known link involves synaptic
      acetylcholinesterase (AChE-S), shown to accelerate amyloid fibrils formation.
      Here, we report that the 'Readthrough' AChE-R splice variant, which differs from
      AChE-S in its 26 C-terminal residues, inversely exerts neuroprotective effects
      from amyloid beta (Abeta) induced toxicity. In vitro, highly purified AChE-R dose
      dependently suppressed the formation of insoluble Abeta oligomers and fibrils and
      abolished Abeta toxicity to cultured cells, competing with the prevalent AChE-S
      protein which facilitates these processes. In vivo, double transgenic APPsw/AChE
      R mice showed lower plaque burden, fewer reactive astrocytes and less dendritic
      damage than single APPsw mice, inverse to reported acceleration of these features
      in double APPsw/AChE-S mice. In hippocampi from Alzheimer's disease patients (n =
      10), dentate gyrus neurons showed significantly elevated AChE-R mRNA and reduced
      AChE-S mRNA. However, immunoblot analyses revealed drastic reductions in the
      levels of intact AChE-R protein, suggesting that its selective loss in the
      Alzheimer's disease brain exacerbates the Abeta-induced damages and revealing a
      previously unforeseen linkage between cholinergic and amyloidogenic events.

PMID- 18056161
TI  - White matter connections reflect changes in voluntary-guided saccades in pre
      symptomatic Huntington's disease.
AB  - Huntington's disease is caused by a known genetic mutation and so potentially can
      be diagnosed many years before the onset of symptoms. Neuropathological changes
      have been found in both striatum and frontal cortex in the pre-symptomatic stage.
      Disruption of cortico-striatal white matter fibre tracts is therefore likely to
      contribute to the first clinical signs of the disease. We analysed diffusion
      tensor MR image (DTI) data from 25 pre-symptomatic gene carriers (PSCs) and 20
      matched controls using a multivariate support vector machine to identify patterns
      of changes in fractional anisotropy (FA). In addition, we performed probabilistic
      fibre tracking to detect changes in 'streamlines' connecting frontal cortex to
      striatum. We found a pattern of structural brain changes that includes putamen
      bilaterally as well as anterior parts of the corpus callosum. This pattern was
      sufficiently specific to enable us to correctly classify 82% of scans as coming
      from a PSC or control subject. Fibre tracking revealed a reduction of frontal
      cortico-fugal streamlines reaching the body of the caudate in PSCs compared to
      controls. In the left hemispheres of PSCs we found a negative correlation between
      years to estimated disease onset and streamlines from frontal cortex to body of
      caudate. A large proportion of the fibres to the caudate body originate from the
      frontal eye fields, which play an important role in the control of voluntary
      saccades. This type of saccade is specifically impaired in PSCs and is an early
      clinical sign of motor abnormalities. A correlation analysis in 14 PSCs revealed
      that subjects with greater impairment of voluntary-guided saccades had fewer
      fibre tracking streamlines connecting the frontal cortex and caudate body. Our
      findings suggest a specific patho-physiological basis for these symptoms by
      indicating selective vulnerability of the associated white matter tracts.

PMID- 18056162
TI  - OEG implantation and step training enhance hindlimb-stepping ability in adult
      spinal transected rats.
AB  - Numerous treatment strategies for spinal cord injury seek to maximize recovery of
      function and two strategies that show substantial promise are olfactory bulb
      derived olfactory ensheathing glia (OEG) transplantation and treadmill step
      training. In this study we re-examined the issue of the effectiveness of OEG
      implantation but used objective, quantitative measures of motor performance to
      test if there is a complementary effect of long-term step training and olfactory
      bulb-derived OEG implantation. We studied complete mid-thoracic spinal cord
      transected adult female rats and compared four experimental groups: media
      untrained, media-trained, OEG-untrained and OEG-trained. To assess the extent of
      hindlimb locomotor recovery at 4 and 7 months post-transection we used three
      quantitative measures of stepping ability: plantar stepping performance until
      failure, joint movement shape and movement frequency compared to sham controls.
      OEG transplantation alone significantly increased the number of plantar steps
      performed at 7 months post-transection, while training alone had no effect at
      either time point. Only OEG-injected rats plantar placed their hindpaws for more
      than two steps by the 7-month endpoint of the study. OEG transplantation combined
      with training resulted in the highest percentage of spinal rats per group that
      plantar stepped, and was the only group to significantly improve its stepping
      abilities between the 4- and 7-month evaluations. Additionally, OEG
      transplantation promoted tissue sparing at the transection site, regeneration of
      noradrenergic axons and serotonergic axons spanning the injury site.
      Interestingly, the caudal stump of media- and OEG-injected rats contained a
      similar density of serotonergic axons and occasional serotonin-labelled
      interneurons. These data demonstrate that olfactory bulb-derived OEG
      transplantation improves hindlimb stepping in paraplegic rats and further suggest
      that task-specific training may enhance this OEG effect.

PMID- 18056163
TI  - Orbitofrontal volume deficit in schizophrenia and thought disorder.
AB  - Orbitofrontal Cortex (OFC) structural abnormality in schizophrenia has not been
      well characterized, probably due to marked anatomical variability and lack of
      consistent definitions. We previously reported OFC sulcogyral pattern alteration
      and its associations with social disturbance in schizophrenia, but OFC volume
      associations with psychopathology and cognition have not been investigated. We
      compared chronically treated schizophrenia patients with healthy control (HC)
      subjects, using a novel, reliable parcellation of OFC subregions and their
      association with cognition, especially the Iowa Gambling Task (IGT), and with
      schizophrenic psychopathology including thought disorder. Twenty-four patients
      with schizophrenia and 25 age-matched HC subjects underwent MRI. OFC Regions of
      Interest (ROI) were manually delineated according to anatomical boundaries: Gyrus
      Rectus (GR); Middle Orbital Gyrus (MiOG); and Lateral Orbital Gyrus (LOG). The
      OFC sulcogyral pattern was also classified. Additionally, MiOG probability maps
      were created and compared between groups in a voxel-wise manner. Both groups
      underwent cognitive evaluations using the IGT, Wisconsin Card Sorting Test, and
      Trail Making Test (TMT). An 11% bilaterally smaller MiOG volume was observed in
      schizophrenia, compared with HC (F(1,47) = 17.4, P = 0.0001). GR and LOG did not
      differ, although GR showed a rightward asymmetry in both groups (F(1,47) = 19.2,
      P < 0.0001). The smaller MiOG volume was independent of the OFC sulcogyral
      pattern, which differed in schizophrenia and HC (chi2 = 12.49, P = 0.002). A
      comparison of MiOG probability maps suggested that the anterior heteromodal
      region was more affected in the schizophrenia group than the posterior paralimbic
      region. In the schizophrenia group, a smaller left MiOG was strongly associated
      with worse 'positive formal thought disorder' (r = -0.638, P = 0.001), and a
      smaller right MiOG with a longer duration of the illness (r = -0.618, P = 0.002).
      While schizophrenics showed poorer performance than HC in the IGT, performance
      was not correlated with OFC volume. However, within the HC group, the larger the
      right hemisphere MiOG volume, the better the performance in the IGT (r = 0.541, P
      = 0.005), and the larger the left hemisphere volume, the faster the switching
      attention performance for the TMT, Trails B (r = -0.608, P = 0.003). The present
      study, applying a new anatomical parcellation method, demonstrated a subregion
      specific OFC grey matter volume deficit in patients with schizophrenia, which was
      independent of OFC sulcogyral pattern. This volume deficit was associated with a
      longer duration of illness and greater formal thought disorder. In HC the finding
      of a quantitative association between OFC volume and IGT performance constitutes,
      to our knowledge, the first report of this association.

PMID- 18056164
TI  - Selective inhibition of fatty acid synthase for lung cancer treatment.
AB  - PURPOSE: Fatty acid synthase (FAS) is overexpressed in many human cancers and is
      considered to be a promising target for therapy. However, in vitro use of
      previous generations of FAS inhibitors has been limited by severe, but
      reversible, anorexia in treated animals, which is thought to be related to a
      parallel stimulation of fatty acid oxidation by these agents. This study
      investigated pharmacologic inhibition of FAS using C93, a rationally designed
      molecule that inhibits FAS activity without affecting fatty acid oxidation in
      preclinical models of lung cancer. EXPERIMENTAL DESIGN: Activity of C93 on FAS
      and fatty acid oxidation was evaluated in cultured non-small cell lung cancer
      (NSCLC) cells. Antineoplastic activity of the compound, given orally or by i.p.
      injection, was evaluated in s.c. and orthotopic NSCLC xenografts. RESULTS: Our
      experiments confirm that C93 effectively inhibits FAS without stimulating fatty
      acid oxidation in lung cancer cells. More importantly, C93 significantly inhibits
      the growth of both s.c. and orthotopic xenograft tumors from human NSCLC cell
      lines without causing anorexia and weight loss in the treated animals.
      CONCLUSIONS: We conclude that inhibition of FAS can be achieved without parallel
      stimulation of fatty acid oxidation and that inhibition of tumor growth in vivo
      can be achieved without anorexia and weight loss. Thus, this therapeutic strategy
      holds promise for clinical treatment of cancers, including non-small cell lung
      cancer, the leading cause of cancer mortality in the United States and Europe.

PMID- 18056165
TI  - The dynamics of estrogen receptor status in breast cancer: re-shaping the
      paradigm.

PMID- 18056166
TI  - Interleukin-21 signaling: functions in cancer and autoimmunity.
AB  - Interleukin-21 (IL-21) is a cytokine with structural and sequence homology to IL
      2 and IL-15, yet possesses several biological properties distinct from these
      cytokines. IL-21 is produced mainly by activated CD4(+) T cells and natural
      killer T cells and mediates its activity by binding to the IL-21 receptor (IL
      21R), consisting of an IL-21-specific alpha chain (IL-21Ralpha; JAK/STAT) that
      heterodimerizes with the common gamma chain (CD132). Intracellular signaling
      occurs through the Janus-activated kinase/signal transducer and activator of
      transcription pathways. Physiologic expression of IL-21R is restricted to
      lymphoid tissues and peripheral blood mononuclear cells; however, other tissues
      such as epithelium, synovium, or transformed cells can acquire expression of both
      components of IL-21R heterodimer. IL-21 has complex activities on a wide variety
      of cell types, leading to enhancement of adaptive T-cell immunity, antibody
      production, activation of natural killer cell subtypes, and opposition to
      suppressive effects mediated by regulatory T cells. Functionally, these
      activities promote immune responses and point to a physiologic role of IL-21 in
      autoimmunity and immune enhancement. Therapeutic manipulation of IL-21 activity
      may allow improved immunotherapy for cancer as well as insights into autoimmune
      disease. Recently conducted phase 1 trials in metastatic melanoma and renal cell
      carcinoma have shown that recombinant IL-21 has a favorable safety profile and
      support its continued investigation as a potential anticancer drug.

PMID- 18056167
TI  - Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic
      biomarker?
AB  - PURPOSE: The combined loss of genetic material on chromosomes 1p and 19q is
      strongly associated with favorable outcome in patients with WHO grade 3
      anaplastic oligodendroglial tumors. The prognostic value of 1p/19q loss in WHO
      grade 2 oligodendroglial tumors is less well defined. Importantly, the possible
      effect of combined 1p/19q loss has not been studied in patients who were not
      treated with radiotherapy or chemotherapy. EXPERIMENTAL DESIGN: Seventy-six
      patients with oligodendroglioma (n = 33), oligoastrocytoma (n = 30), anaplastic
      oligodendroglioma (n = 6), or anaplastic oligoastrocytoma (n = 7) were identified
      who had not received radiotherapy or chemotherapy after their first operation
      until the end of follow-up or until the first progression and had tissue for
      1p/19q status available. 1p/19q status was assessed by multiplex ligation
      dependent probe amplification. RESULTS: After a median follow-up of 3.8 years,
      progressive disease was documented in 34 patients. The estimated median
      progression-free survival was 4.6 years. Fifty-eight of the 76 patients had a
      combined loss of 1p and 19q. The absence or presence of combined 1p/19q loss was
      not prognostic for progression-free survival using multivariate adjustment for
      histology, extent of resection, and gender. CONCLUSIONS: Combined 1p/19q loss is
      not a sensitive prognostic biomarker in patients with oligodendroglial tumors who
      do not receive radiotherapy or chemotherapy. The gene products lost as a
      consequence of this codeletion may include mediators of resistance to genotoxic
      therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion
      promoting the formation of glial neoplasms, which retain high sensitivity to
      genotoxic stress.

PMID- 18056168
TI  - E2F1 overexpression correlates with thymidylate synthase and survivin gene
      expressions and tumor proliferation in non small-cell lung cancer.
AB  - PURPOSE: We investigated the clinical significance of E2F1 gene expression in
      relation to its target genes, thymidylate synthase (TS) and Survivin, in case of
      non-small-cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: One hundred twenty-seven
      cases of resected NSCLC were analyzed. Quantitative reverse transcription-PCR was
      done to evaluate the gene expression of E2F1, TS, and Survivin.
      Immunohistochemistry was done to investigate the protein expression of E2F1, TS,
      and Survivin. The Ki-67 proliferation index and the apoptotic index using the
      terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling method
      were also evaluated. RESULTS: E2F1 gene expression significantly correlated with
      the Ki-67 proliferation index (r = 0.487; P < 0.0001), although no correlation
      was observed between E2F1 gene expression and the apoptotic index. With regard to
      E2F1 target genes, E2F1 gene expression significantly correlated with TS gene
      expression (r = 0.709; P < 0.0001) and Survivin gene expression (r = 0.403; P <
      0.0001). The overall survival rate was significantly lower in patients with high
      E2F1 tumors than in those with low-E2F1 tumors (P = 0.0027), especially among
      patients with stage II to III NSCLCs (P = 0.0188). A Cox regression analysis
      showed that the E2F1 status was a significant prognostic factor for NSCLC
      patients (hazard ratio, 2.052; P = 0.0261). CONCLUSIONS: The present study
      revealed that E2F1 gene expression correlates with TS and Survivin gene
      expressions and tumor proliferation. During the progression of NSCLC, E2F1
      overexpression could produce more aggressive tumors with a high proliferation
      rate and chemoresistance.

PMID- 18056169
TI  - CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer.
AB  - PURPOSE: Although elevated proportions of CD4(+)CD25(+) regulatory T (Treg) cells
      have been shown in several types of cancers, very little is known about the
      existence and function of CD8(+) Treg cells in prostate cancer. In this study, we
      investigated prostate tumor-derived CD8(+) Treg cells and their function.
      EXPERIMENTAL DESIGN: Tumor-infiltrating lymphocytes (TIL) from fresh tumor
      specimens of patients with prostate cancer were generated and subjected to
      phenotypic and suppressive function analyses. In particular, we investigated the
      role and function CD8(+) Treg cells in prostate cancer. RESULTS: We show that
      high percentages of CD4(+)CD25(+) T cells are probably present in the majority
      (70%) of prostate TILs. Remarkably, both CD4(+) and CD8(+) T-cell subpopulations
      possessed potent suppressive activity. T-cell cloning and fluorescence-activated
      cell sorting analyses showed the presence of CD8(+)CD25(+) Treg cell clones that
      expressed FoxP3 and suppressed naive T-cell proliferation, in addition to the
      previously known CD4(+)CD25(+) Treg cells. These CD8(+) Treg cells suppressed
      naive T-cell proliferation mainly through a cell contact-dependent mechanism.
      Importantly, the suppressive function of CD8(+) Treg cells could be reversed by
      human Toll-like receptor 8 (TLR8) signaling. CONCLUSION: Our study shows that
      like CD4(+)CD25(+) Treg cells, CD8(+) Foxp3(+) Treg cells present in prostate
      tumor-derived TILs suppress immune responses and that their suppressive function
      can be regulated by TLR8 ligands, raising the possibility that the manipulation
      of Treg cell function by TLR8 ligands could improve the efficacy of immunotherapy
      for prostate cancer patients.

PMID- 18056170
TI  - Prognostic role of HuR in hereditary breast cancer.
AB  - PURPOSE: HuR is an mRNA-binding protein that enhances the stability of certain
      transcripts and can regulate their translation. Elevated cytoplasmic expression
      of HuR protein has been linked to carcinogenesis and is associated with reduced
      survival in breast, ovarian, and gastric adenocarcinomas. EXPERIMENTAL DESIGN:
      Here, we have explored the relevance of HuR in familial breast cancer. Tumor
      samples were collected from patients with identified BRCA1 (n = 51) or BRCA2 (n =
      47) mutations or familial non-BRCA1/2 cases (n = 525), and analyzed by
      immunohistochemistry. RESULTS: Among familial non-BRCA1/2 breast cancer patients,
      cytoplasmic HuR protein expression was present in 39.4% of the cases and was
      associated with estrogen receptor negativity, progesterone receptor negativity,
      p53 positivity, high tumor grade, and ductal type of the tumor. In multivariate
      analysis, cytoplasmic HuR expression was an independent marker of reduced
      survival in the non-BRCA1/2 group along with tumor size >2 cm, lymph node
      metastasis, and high histologic grade. In patients with BRCA1 or BRCA2 mutations,
      cytoplasmic HuR expression was more frequent (62.7% for BRCA1 and 61.7% for
      BRCA2) than in the non-BRCA1/2 group, but in BRCA-mutated subgroups cytoplasmic
      HuR expression did not associate with survival. CONCLUSIONS: Our results show
      that HuR is an important prognostic factor in familial breast cancer patients and
      may contribute to carcinogenesis in this disease.

PMID- 18056171
TI  - Notch-1 mutations are secondary events in some patients with T-cell acute
      lymphoblastic leukemia.
AB  - PURPOSE: Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic
      leukemia (T-ALL), occurring in >50% of patients. In murine models of T-ALL, Notch
      1 activation can both directly initiate leukemia and cooperate secondarily to
      other primary events. Whether acquisition of Notch-1 mutations is an early
      initiating event or a secondary event in the pathogenesis of human T-ALL is
      unclear. EXPERIMENTAL DESIGN: We used denaturing high-performance liquid
      chromatography, sequencing, and fragment analysis to analyze Notch-1 mutational
      status and mutant level in 62 patients at presentation as well as 16 matched
      presentation-relapse samples. RESULTS: We detected Notch-1 mutations in 47
      patients (76%). Seven of these were low-level mutations (quantified at < or
      =10%), despite high blast counts, suggesting that they were acquired as a
      secondary event in a subclone. Of 16 matched presentation-relapse samples
      studied, 7 were wild-type at both presentation and relapse. Five of nine mutant
      positive patients at presentation relapsed with the same mutation(s) at the same
      high level. Four patients had evidence of a change in mutant at relapse. One lost
      a PEST mutation and became wild-type. Two others lost mutations at relapse but
      acquired different mutations, despite unchanged T-cell receptor rearrangements,
      suggesting that the latter event predated the acquisition of the Notch-1
      mutation. One relapsed with a secondary T-cell leukemia and different Notch
      mutation. CONCLUSIONS: These results suggest that Notch-1 mutations can sometimes
      be acquired as secondary events in leukemogenesis and must be used cautiously as
      solitary minimal residual disease markers.

PMID- 18056172
TI  - Stem cell marker nestin and c-Jun NH2-terminal kinases in tumor and peritumor
      areas of glioblastoma multiforme: possible prognostic implications.
AB  - PURPOSE: It has been hypothesized that brain tumors are derived from stem cell or
      transiently dividing precursor transformation. Furthermore, c-Jun NH(2)-terminal
      kinases (JNKs) have been involved in gliomagenesis. This study analyzes stem cell
      marker nestin and JNK expression in glioblastoma multiforme (GBM) and peritumor
      tissue and assesses their possible prognostic implications. EXPERIMENTAL DESIGN:
      Nestin and both total JNK (tJNK) and phosphorylated JNK (pJNK) expression was
      investigated by immunohistochemistry in 20 GBMs. Samples were derived from tumors
      (first area), from tissues at a distance <1 cm (second area), and between 1 and
      3.5 cm (third area) from the macroscopic tumor border. The relationships between
      patients' age, Karnofsky performance status, gender, protein expression, and
      survival were analyzed. RESULTS: Nestin cytoplasmic immunoreactivity was observed
      in the majority of cells in tumor but infrequently in peritumor areas. tJNK,
      observed in the nucleus and cytoplasm, was widely expressed in the three areas;
      pJNK, mostly located in the nuclei, was found in a variable percentage of cells
      in the tumor and peritumor tissue. Nestin and JNK expression in peritumor areas
      was independent of the presence of neoplastic cells. Univariate analysis
      indicated that survival was longer (19 versus 12 months; P = 0.01) for patients
      whose pJNK/nestin and (pJNK/tJNK)/nestin ratios in the second area were > or
      =2.619 and > or =0.026, respectively. The same variables showed an independent
      prognostic value in multivariate analysis. CONCLUSIONS: Nestin and JNK expression
      indicates that peritumor tissue, independently of the presence of neoplastic
      cells, may present signs of transformation. Moreover, pJNK/nestin and
      (pJNK/tJNK)/nestin ratios in that tissue seem to have some prognostic
      implications in GBM patients.

PMID- 18056173
TI  - Novel markers of subclinical disease for Ewing family tumors from gene expression
      profiling.
AB  - PURPOSE: Targeting subclinical disease in the bone marrow is particularly
      relevant in metastatic Ewing family tumors (EFT) where cure is difficult. Genome
      wide expression arrays can uncover novel genes differentially expressed in tumors
      over normal marrow/blood, which may have potentials as markers of subclinical
      disease. EXPERIMENTAL DESIGN: Gene expression array data were obtained on 28 EFT
      tumors using the Affymetrix U133 gene chip and compared with 10 normal blood
      samples. Ten genes with high tumor to blood ratios were identified. Quantitative
      reverse transcription-PCR was done to study (a) the dynamic range of detection of
      rare tumor cells, (b) the gene expression in normal blood/marrow samples, (c) the
      gene expression among EFT tumors, and (d) the detection and prognostic impact of
      marker positivity in histology-negative diagnostic marrows of EFT patients.
      RESULTS: Five of 10 genes (i.e., six-transmembrane epithelial antigen of the
      prostate 1 [STEAP1], cyclin D1 [CCND1], NKX2-2 transcription factor [NKX2-2],
      plakophilin 1 [PKP1], and transmembrane protein 47 [TMEM47]) were chosen for
      further analyses based on their steep linear dynamic range in detecting tumor
      cells seeded in normal mononuclear cells and on their homogeneous expression
      among EFT tumors. Prognostic effect was evaluated in 35 histology-negative
      diagnostic marrows. Marker negativity of STEAP1, CCND1, or NKX2-2, as well as
      three markers in combination, was strongly correlated with patient survival as
      well as survival without new metastases. CONCLUSIONS: This gene expression array
      based approach identified novel markers that may be informative at diagnosis for
      risk group assessment. Their clinical utility needs to be tested in large patient
      cohorts.

PMID- 18056174
TI  - A multiparametric panel for ovarian cancer diagnosis, prognosis, and response to
      chemotherapy.
AB  - PURPOSE: Our goal was to examine a panel of 11 biochemical variables, measured in
      cytosolic extracts of ovarian tissues (normal, benign, and malignant) by
      quantitative ELISAs for their ability to diagnose, prognose, and predict response
      to chemotherapy of ovarian cancer patients. EXPERIMENTAL DESIGN: Eleven proteins
      were measured (9 kallikreins, B7-H4, and CA125) in cytosolic extracts of 259
      ovarian tumor tissues, 50 tissues from benign conditions, 35 normal tissues, and
      44 tissues from nonovarian tumors that metastasized to the ovary. Odds ratios and
      hazard ratios and their 95% confidence interval were calculated. Time-dependent
      receiver operating characteristic curves for censored survival data were used to
      evaluate the performance of the biomarkers. Resampling was used to validate the
      performance. RESULTS: Most biomarkers effectively separated cancer from noncancer
      groups. A composite marker provided an area under the curve of 0.97 (95%
      confidence interval, 0.95-0.99) for discriminating normal and cancer groups.
      Univariately, hK5 and hK6 were positively associated with progression. After
      adjusting for clinical variables in multivariate analysis, both hK10 and hK11
      significantly predicted time to progression. Increasing levels of hK13 were
      associated with chemotherapy response, and the predictive power of hK13 to
      chemotherapy response was improved by a panel of five biomarkers. CONCLUSIONS:
      The evidence shows that a group of kallikreins and multiparametric combinations
      with other biomarkers and clinical variables can significantly assist with
      ovarian cancer classification, prognosis, and response to platinum-based
      chemotherapy. In particular, we developed a multiparametric strategy for
      predicting ovarian cancer response to chemotherapy, comprising several biomarkers
      and clinical features.

PMID- 18056175
TI  - Expression of indoleamine 2,3-dioxygenase in tumor endothelial cells correlates
      with long-term survival of patients with renal cell carcinoma.
AB  - PURPOSE: The inflammatory enzyme indoleamine 2,3-dioxygenase (IDO) participates
      in immune tolerance and tumor immune escape processes by degradation of the
      essential amino acid tryptophan and formation of toxic catabolites. Here, we
      analyzed the role of IDO in tumor growth and disease progression in patients with
      clear cell renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: Expression of IDO
      mRNA was analyzed by quantitative reverse transcription-PCR in 55 primary and 52
      metastatic RCC, along with 32 normal kidneys. Western blot and
      immunohistochemistry analyses were used to semiquantitatively determine IDO
      proteins in a subset of tumor samples, in RCC cell lines, and microvessel
      endothelial cells. IDO expression was correlated with expression of the
      proliferation marker Ki67 in tumor cells and survival of patients with tumor.
      RESULTS: More than 75% of the clear cell RCC in comparison to normal kidney
      contained elevated levels of IDO mRNA, which correlated with their IDO protein
      content. Low IDO mRNA levels in primary tumors represented an unfavorable
      independent prognostic factor (hazard ratio, 3.8; P = 0.016). Unexpectedly,
      immunohistochemical analyses revealed that IDO is nearly exclusively expressed in
      endothelial cells of newly formed blood vessels and is virtually absent from
      tumor cells, although RCC cells could principally synthesize IDO as shown by in
      vitro stimulation with IFN-gamma. A highly significant inverse correlation
      between the density of IDO-positive microvessels and the content of proliferating
      Ki67-positive tumor cells in primary and metastatic clear cell RCC was found (P =
      0.004). CONCLUSIONS: IDO in endothelial cells might limit the influx of
      tryptophan from the blood to the tumor or generate tumor-toxic metabolites, thus
      restricting tumor growth and contributing to survival.

PMID- 18056176
TI  - A switch from E-cadherin to N-cadherin expression indicates epithelial to
      mesenchymal transition and is of strong and independent importance for the
      progress of prostate cancer.
AB  - PURPOSE: Cell adhesion molecules are of crucial importance in cancer invasion and
      metastasis. Epithelial to mesenchymal transition, characterized by reduced E
      cadherin and increased N-cadherin expression, has been recognized as a feature of
      aggressive tumors, but the importance of this phenotype has not been settled in
      human prostate cancer. We here present novel data, with special focus on the
      independent relationship between an E-cadherin to N-cadherin switch (EN-switch)
      and patient prognosis. EXPERIMENTAL DESIGN: Tissue microarray sections from a
      consecutive series of 104 radical prostatectomies during 1988 to 1994 with
      detailed clinicopathologic data and long follow-up were studied
      immunohistochemically for the expression of E-cadherin, N-cadherin, P-cadherin,
      beta-catenin, and p120(CTN). RESULTS: Low E-cadherin expression was significantly
      associated with adverse clinicopathologic features, whereas other biomarkers were
      mostly related to Gleason score. In univariate survival analyses, cadherin
      switching (high N-cadherin and low E-cadherin) showed strong and significant
      associations with multiple end points of progression and cancer-specific death.
      Expression of the "basal cell marker" P-cadherin was associated with shorter time
      to skeletal metastasis (P = 0.036). In multivariate analysis of time to clinical
      recurrence, the "EN-switch" (hazard ratio, 4.3; P < 0.0005) had strong and
      independent prognostic effect, together with Gleason score. CONCLUSION: These
      novel data unravel the importance of epithelial to mesenchymal transition for
      prostate cancer progression, and demonstration of a switch from E-cadherin to N
      cadherin expression could have significant effect on the care of prostate cancer
      patients.

PMID- 18056177
TI  - Inhibition of the intrinsic apoptosis pathway downstream of caspase-9 activation
      causes chemotherapy resistance in diffuse large B-cell lymphoma.
AB  - PURPOSE: Inhibition of the apoptosis cascade is an important cause of therapy
      resistance in diffuse large B-cell lymphomas (DLBCL). In this study, we
      investigated possible mechanisms and expression levels of apoptosis-related genes
      in the apoptosis pathway that may be responsible for differences in chemotherapy
      sensitivity between DLBCL patients. EXPERIMENTAL DESIGN: Twenty-eight DLBCL
      patient samples were investigated for their expression levels of apoptosis
      related genes using reverse transcription-multiplex ligation-dependent probe
      amplification analysis. Functional analysis of the intrinsic, caspase-9-mediated
      pathway was done using fluorescence-activated cell sorting analysis, Western blot
      analysis, and immunohistochemistry. RESULTS: Two DLBCL groups were identified:
      one with low expression levels of both proapoptotic and antiapoptotic genes and
      one group with high expression levels of these genes. DLBCL with high expression
      levels of proapoptotic and antiapoptotic genes frequently seemed to be refractory
      to clinical chemotherapy. Functional analysis in these latter DLBCL samples and
      DLBCL cell lines with comparable expression profiles revealed high levels of
      spontaneous caspase-9 activity without induction of apoptosis, indicating
      disruption of the apoptosis pathway downstream of caspase-9 activation. This
      disruption of the apoptosis pathway could be restored using a small-molecule XIAP
      antagonist. CONCLUSIONS: We conclude that the intrinsic, caspase-9-mediated
      apoptosis pathway is constitutively activated in part of chemotherapy-refractory
      DLBCL with concomitant downstream inhibition of the convergence apoptosis pathway
      and that inhibition of XIAP might be an alternative therapy for chemotherapy
      refractory DLBCL.

PMID- 18056178
TI  - Gain of 1q is a potential univariate negative prognostic marker for survival in
      medulloblastoma.
AB  - PURPOSE: Tumor risk stratification during diagnosis is paramount for children
      with medulloblastomas, primarily because very young patients (<3 years) suffer
      cognitive deficits from radio- and chemotherapy sequelae. Thus, distinguishing
      tumors that are biologically more aggressive is essential for medulloblastoma
      management to maximize the delay in radiation treatment without adversely
      affecting survival outcome. In this context, current strategies for risk
      assessment, which are based on clinical parameters, remain unsatisfactory.
      EXPERIMENTAL DESIGN: Array-based comparative genomic hybridization (aCGH) was
      used to identify chromosomal copy number abnormalities in a cohort of 49
      medulloblastoma tumors. Based on the karyotypes generated from aCGH analysis,
      each tumor was scored for copy number abnormalities, and the log-rank test was
      used to evaluate whether any cytogenetic events were associated with survival.
      RESULTS: A single copy gain of 1q was shown to be a negative prognostic marker
      for survival in medulloblastomas with high statistical significance (P < 0.0001,
      log-rank test). CONCLUSION: A gain of 1q provides a potential means of predicting
      overall survival in medulloblastoma.

PMID- 18056179
TI  - Reversal of the estrogen receptor negative phenotype in breast cancer and
      restoration of antiestrogen response.
AB  - PURPOSE: In breast cancer, the presence of estrogen receptor alpha (ER) denotes a
      better prognosis and response to antiestrogen therapy. Lack of ERalpha correlates
      with overexpression of epidermal growth factor receptor or c-erbB-2. We have
      shown that hyperactivation of mitogen-activated protein kinase (MAPK) directly
      represses ERalpha expression in a reversible manner. In this study, we determine
      if inhibition of MAPK in established ERalpha(-) breast cancer cell lines and
      tumors results in reexpression of ERalpha, and further, if reexpression of
      ERalpha in these ERalpha(-) tumors and cell lines could restore antiestrogen
      responses. EXPERIMENTAL DESIGN: Established ERalpha(-) breast cancer cell lines,
      ERalpha(-) breast tumors, and tumor cell cultures obtained from ERalpha(-) tumors
      were used in this study. Inhibition of hyperactive MAPK was accomplished via the
      MAPK/ERK kinase 1/2 inhibitor U0126 or via upstream inhibition with Iressa or
      Herceptin. Western blotting or reverse transcription-PCR for ERalpha was used to
      assess the reexpression of ERalpha in cells treated with U0126. Growth assays
      with WST-1 were done to assess restoration of antiestrogen sensitivity in these
      cells. RESULTS: Inhibition of MAPK activity in ERalpha(-) breast cancer cell
      lines results in reexpression of ERalpha; upstream inhibition via targeting
      epidermal growth factor receptor or c-erbB-2 is equally effective. Importantly,
      this reexpressed ERalpha can now mediate an antiestrogen response in a subset of
      these ERalpha(-) breast cancer cell lines. Treatment of ERalpha(-) tumor
      specimens with MAPK inhibitors results in restoration of ERalpha mRNA, and
      similarly in epithelial cultures from ERalpha(-) tumors, MAPK inhibition restores
      both ERalpha protein and antiestrogen response. CONCLUSIONS: These data show both
      the possibility of restoring ERalpha expression and antiestrogen responses in
      ERalpha(-) breast cancer and suggest that there exist ERalpha(-) breast cancer
      patients who would benefit from a combined MAPK inhibition/hormonal therapy.

PMID- 18056180
TI  - Telomere DNA content predicts breast cancer-free survival interval.
AB  - BACKGROUND: Telomeres are nucleoprotein complexes that protect chromosome ends
      from degradation and recombination. Critically shortened telomeres generate
      genomic instability. It has been postulated that the extent of telomere DNA loss
      is related to the degree of genomic instability within a tumor and therefore may
      presage clinical outcome. The objective of this investigation was to evaluate the
      hypothesis that telomere DNA content (TC) in breast tumor tissues predicts breast
      cancer-free survival interval. MATERIALS AND METHODS: Slot blot titration assay
      was used to quantitate TC in 530 archival breast tumor tissues in a population
      based cohort. The relationships between TC, 12 risk factors for breast cancer
      adverse events (i.e., death due to breast cancer, breast cancer recurrence, or
      development of a new primary breast tumor), and breast cancer-free survival
      interval were evaluated by Fisher's exact test, log-rank analysis, and univariate
      and multivariate Cox proportional hazards models. RESULTS: TC was independent of
      each of the 12 risk factors. Ethnicity, tumor-node-metastasis stage, estrogen
      receptor, progesterone receptor, and p53 status, chemotherapy sequence, adjuvant
      therapy, and TC each conferred significant relative hazards. The best overall
      multivariate Cox proportional hazards model included TC, p53 status, tumor-node
      metastasis stage, and estrogen receptor status as independent predictors of
      breast cancer-free survival interval (P < 0.00005). Low TC (< or =200% of
      standard), relative to the high-TC group (>200% of standard), conferred an
      adjusted relative hazard of 2.88 (95% confidence interval, 1.16-7.15; P = 0.022)
      for breast cancer-related adverse events. CONCLUSIONS: TC in breast cancer tissue
      is an independent predictor in this group of breast cancer-free survival
      interval.

PMID- 18056181
TI  - NOXA and PUMA expression add to clinical markers in predicting biochemical
      recurrence of prostate cancer patients in a survival tree model.
AB  - PURPOSE: To assess the expression of proapoptotic NOXA and PUMA in prostate
      tissues and delineate their association with prostate cancer (PCa) recurrence.
      EXPERIMENTAL DESIGN: Normal, prostatic intraepithelial neoplasia (PIN), hormone
      sensitive (HS) PCa, and hormone-refractory (HR) PCa tissues were used to build
      tissue microarrays encompassing a total of 135 patients. Two observers assessed
      the intensity of NOXA and PUMA immunohistochemical staining using a composite
      color scale. One hundred and eighty recursive partitioning and regression tree
      (RPART) models were generated to predict biochemical recurrence (BCR) within HS
      cancer patients using NOXA, PUMA, and clinical parameters. Models were then
      ranked according to the integrated Brier score (IBS). RESULTS: Increasing NOXA
      expression was associated with PCa progression, reaching the highest levels in HR
      PCa. Increased NOXA expression was observed in 68% of HS cancer patients and was
      predictive of BCR (LR = 8.64; P = 0.003). In contrast, PUMA expression was
      highest in HS cancer, and although 70% of HS cancer patients exhibited increased
      PUMA expression, PUMA alone could not predict the onset of BCR. Interestingly,
      the top-ranking RPART model generated [IBS = 0.107; 95% confidence interval (95%
      CI), 0.065-0.128] included surgical margin status and NOXA and PUMA expression,
      although recurrent prognostic classification schemes obtained in the top 10
      models favored a survival tree model containing margin status, NOXA expression,
      and preoperative prostate-specific antigen (PSA) (IBS = 0.114; 95% CI, 0.069
      0.142). CONCLUSION: We conclude that NOXA and PUMA expression may be linked to
      PCa progression and propose further validation of a survival tree model including
      surgical margin status, NOXA expression, and preoperative PSA for predicting BCR.

PMID- 18056182
TI  - Circulating tumor cell number and prognosis in progressive castration-resistant
      prostate cancer.
AB  - PURPOSE: The development of tumor-specific markers to select targeted therapies
      and to assess clinical outcome remains a significant area of unmet need. We
      evaluated the association of baseline circulating tumor cell (CTC) number with
      clinical characteristics and survival in patients with castrate metastatic
      disease considered for different hormonal and cytotoxic therapies. EXPERIMENTAL
      DESIGN: CTC were isolated by immunomagnetic capture from 7.5-mL samples of blood
      from 120 patients with progressive clinical castrate metastatic disease. We
      estimated the probability of survival over time by the Kaplan-Meier method. The
      concordance probability estimate was used to gauge the discriminatory strength of
      the informative prognostic factors. RESULTS: Sixty-nine (57%) patients had five
      or more CTC whereas 30 (25%) had two cells or less. Higher CTC numbers were
      observed in patients with bone metastases relative to those with soft tissue
      disease and in patients who had received prior cytotoxic chemotherapy relative to
      those who had not. CTC counts were modestly correlated to measurements of tumor
      burden such as prostate-specific antigen and bone scan index, reflecting the
      percentage of boney skeleton involved with tumor. Baseline CTC number was
      strongly associated with survival, without a threshold effect, which increased
      further when baseline prostate-specific antigen and albumin were included.
      CONCLUSIONS: Baseline CTC was predictive of survival, with no threshold effect.
      The shedding of cells into the circulation represents an intrinsic property of
      the tumor, distinct from extent of disease, and provides unique information
      relative to prognosis.

PMID- 18056183
TI  - Sequential influences of leukemia-specific and genetic factors on p-glycoprotein
      expression in blasts from 817 patients entered into the National Cancer Research
      Network acute myeloid leukemia 14 and 15 trials.
AB  - PURPOSE: P-glycoprotein (Pgp) is a major prognostic factor for chemotherapy
      failure in acute myeloid leukemia (AML). This study compared the influence of
      genetic and leukemia-specific factors on Pgp. EXPERIMENTAL DESIGN: Eight hundred
      and seventeen samples were studied prospectively for Pgp protein expression and
      function and G1199A, G2677T, and C3435T polymorphisms in the encoding gene ABCB1.
      RESULTS: Age, low WBC count, high bcl-2, secondary AML and myelodysplastic
      syndrome, and adverse cytogenetics all correlated strongly with high Pgp (MRK16)
      protein expression. However, ABCB1 3435TT homozygosity was negatively correlated
      with Pgp. Pgp protein is only expressed in 41% of samples such that the negative
      effect of the polymorphism was not seen at baseline Pgp levels but was marked in
      the upper 41% of samples (MRK16 Deltamean fluorescence intensity of 75th centile
      sample = 9 units for TT variant samples and 26 units for CC/CT; P = 0.003).
      However, no association was found between genetic factors and Pgp function using
      rhodamine 123 accumulation. CONCLUSIONS: The genetic polymorphism 3435TT (which
      results in unstable mRNA) has a significant effect on Pgp expression, but this is
      only seen in approximately 40% of cases in which mRNA and protein are detectable.
      Moreover, leukemia-specific factors, such as low WBC count and poor risk
      cytogenetics, have a much greater effect than genetic polymorphisms on Pgp
      expression in AML blasts.

PMID- 18056184
TI  - High-risk human papillomavirus E7 oncoprotein detection in cervical squamous cell
      carcinoma.
AB  - PURPOSE: Persistent infections by high-risk human papillomavirus (HPV) types are
      the main etiologic factor for cervical cancer. The objective of this study was to
      evaluate whether high-risk E7 oncoprotein is adequate as a marker for the
      detection of cervical cancer. EXPERIMENTAL DESIGN: HPV typing was done in
      biopsies from 58 cervical carcinoma and 22 normal cervical squamous epithelia.
      The HPV-16 E7, HPV-18 E7, and HPV-45 E7 oncoprotein levels were monitored by
      immunohistochemistry and compared with those of p16(INK4a) and Ki67. RESULTS:
      Fifty-five (94.8%) tumors were high-risk HPV-DNA-positive (46 HPV-16, 2 HPV-16
      and HPV-18, 4 HPV-18, 1 HPV-33, and 2 HPV-45). HPV-DNA could not be detected in
      three tumors (5.2%). High HPV E7 oncoprotein levels were shown in 57 cervical
      cancers (98.3%), without correlation between expression levels and tumor stages.
      CONCLUSION: This is the first study which systematically analyzes the levels of
      the major HPV oncoproteins in cervical carcinomas demonstrating that the high
      risk HPV E7 proteins are regularly expressed in these cancers. This suggests that
      high-risk E7 oncoproteins are necessary for cervical cancers and apparently
      essential as tumor marker.

PMID- 18056185
TI  - Benefit of complete response in multiple myeloma limited to high-risk subgroup
      identified by gene expression profiling.
AB  - EXPERIMENTAL DESIGN: To determine whether the clinical benefit of complete
      remission (CR) may depend on prognostic subgroups of patients with multiple
      myeloma. PATIENTS AND METHODS: Newly diagnosed patients with myeloma received a
      tandem autotransplant regimen. Using multivariate regression analyses, we
      examined the prognostic implications of time-dependent onset of CR on overall
      survival and event-free survival in the context of standard prognostic factors
      (SPF) and gene expression profiling-derived data available for 326 patients.
      RESULTS: CR benefited patients regardless of risk status when only SPFs were
      examined. With knowledge of gene array data, a survival (and event-free survival)
      benefit of CR only pertained to the small high-risk subgroup of 13% of patients
      (hazard ratio, 0.23; P = 0.001), whereas the majority of patients with low-risk
      disease had similar survival expectations whether or not CR was achieved (hazard
      ratio, 0.68; P = 0.128). CONCLUSIONS: Access to gene expression information
      permitted the recognition of a small very high-risk subgroup of 13% of patients,
      in whom prolonged survival critically depended on achieving CR. Absence of such
      benefit in the remainder should lead to a reassessment of clinical trial designs
      that rely on this end point as a surrogate for long-term prognosis.

PMID- 18056186
TI  - BCR-ABL messenger RNA levels continue to decline in patients with chronic phase
      chronic myeloid leukemia treated with imatinib for more than 5 years and
      approximately half of all first-line treated patients have stable undetectable
      BCR-ABL using strict sensitivity criteria.
AB  - PURPOSE: In the first years of imatinib treatment, BCR-ABL remained detectable in
      all but a small minority of patients with chronic myeloid leukemia. We determined
      whether BCR-ABL continues to decline with longer imatinib exposure and the
      incidence and consequence of undetectable BCR-ABL. EXPERIMENTAL DESIGN: BCR-ABL
      levels were measured in a subset of 53 imatinib-treated IRIS trial patients for
      up to 7 years (29 first-line, 24 second-line). Levels were deemed undetectable
      using strict PCR sensitivity criteria. RESULTS: By 18 months, the majority
      achieved a 3-log reduction [major molecular response (MMR)]. BCR-ABL continued to
      decline but at a slower rate (median time to 4-log reduction and undetectable BCR
      ABL of 45 and 66 months for first-line). The probability of undetectable BCR-ABL
      increased considerably from 36 to 81 months of first-line imatinib {7% [95%
      confidence interval (95% CI), 0-17%] versus 52% (95% CI, 32-72%)}. Undetectable
      BCR-ABL was achieved in 18 of 53 patients and none of these 18 lost MMR after a
      median follow-up of 33 months. Conversely, MMR was lost in 6 of 22 (27%) patients
      with sustained detectable BCR-ABL and was associated with BCR-ABL mutations in 3
      of 6. Loss of MMR was recently defined as suboptimal imatinib response. There was
      no difference in the probability of achieving molecular responses between first-
      and second-line patients but first-line had a significantly higher probability of
      maintaining MMR [P = 0.03; 96% (95% CI, 88-100%) versus 71% (95% CI, 48-93%)].
      CONCLUSIONS: With prolonged therapy, BCR-ABL continued to decline in most
      patients and undetectable BCR-ABL was no longer a rare event. Loss of MMR was
      only observed in patients with sustained detectable BCR-ABL.

PMID- 18056187
TI  - Pilot study of neoadjuvant treatment with erlotinib in nonmetastatic head and
      neck squamous cell carcinoma.
AB  - PURPOSE: To determine the safety and efficacy of erlotinib given as neoadjuvant
      treatment in patients with head and neck squamous cell carcinoma (HNSCC). Further
      objectives were to identify markers of response to erlotinib and to assess the
      pharmacodynamic effects of erlotinib in tumor cells. EXPERIMENTAL DESIGN:
      Patients with locally advanced nonmetastatic HNSCC were treated with erlotinib
      150 mg daily pending surgical management. Tumor samples were collected before and
      after erlotinib treatment and were analyzed using immunohistochemistry. Epidermal
      growth factor receptor copy number was determined in tumors using CISH analysis.
      RESULTS: Between November 2003 and December 2005, 35 patients were included in
      the study. Neoadjuvant treatment with erlotinib in HNSCC patients was well
      tolerated and did not necessitate modification to routine surgical procedures.
      Among 31 evaluable patients, erlotinib was given for a median of 20 days. At the
      time of surgery, tumor shrinkage was observed in nine patients (29%).
      Immunohistochemistry analyses were done for 31 patients and showed a decrease in
      phosphorylated tyrosine residues and phosphorylated erk immunostaining after
      erlotinib treatment. In a retrospective analysis, baseline p21(waf) expression in
      the basal-like cell layer was statistically positively correlated with clinical
      response to treatment. Epidermal growth factor receptor copy number did not
      correlate with response to erlotinib. CONCLUSION: Neoadjuvant treatment of HNSCC
      with erlotinib was well tolerated. Baseline p21(waf) expression was associated
      with response to erlotinib and so might be useful as a tool to select patients
      for erlotinib therapy in this setting.

PMID- 18056188
TI  - Glucocorticoids in the treatment of children with acute lymphoblastic leukemia
      and hodgkin's disease: a pilot study on the adverse psychological reactions and
      possible associations with neurobiological, endocrine, and genetic markers.
AB  - PURPOSE: We did a controlled study to assess adverse psychological reactions
      (APR) associated with high-dose glucocorticoid therapy and tried to detect
      somatic correlates for the observed reactions. PATIENTS AND METHODS: Our study
      included 37 patients with acute lymphoblastic leukemia (ALL) and 11 patients with
      Morbus Hodgkin (MH) disease, who were treated with high-dose glucocorticoid
      therapy, and 26 control patients with other types of malignancies. APRs were
      assessed with a standardized measure via parent-report. Patients with ALL and MH
      were further analyzed for signs of neuronal cell death in the cerebrospinal
      fluid, polymorphisms of the glucocorticoid receptor gene, as well as cortisol,
      adrenocorticorticotropic hormone, and dehydroepiandrosterone sulfate blood
      levels. RESULTS: Fifty-four percent of ALL, 36% of MH, and 23% of control
      patients developed APR in the first few weeks of therapy. Approximately 3.5
      months later, the majority of patients with ALL showed no APR, similar to control
      patients. Patients demonstrating a higher, nonsuppressible secretion of cortisol
      and/or adrenocorticorticotropic hormone during glucocorticoid therapy were found
      to be more likely to develop APR. No sign of neuronal cell destruction and no
      correlation of APR with specific glucocorticoid receptor polymorphisms were
      found. CONCLUSION: Our results suggest that the development of APR due to
      glucocorticoid therapy is measurable and correlates with hormonal reaction
      patterns.

PMID- 18056189
TI  - A phase I trial of lenalidomide in patients with recurrent primary central
      nervous system tumors.
AB  - PURPOSE: Inhibition of angiogenesis represents a promising new therapeutic
      strategy for treating primary malignant brain tumors. Lenalidomide, a potent
      analogue of the antiangiogenic agent thalidomide, has shown significant activity
      in several hematologic malignancies, and therefore we chose to explore its
      tolerability and activity in patients with primary central nervous system tumors.
      EXPERIMENTAL DESIGN: A phase I interpatient dose escalation trial of lenalidomide
      in patients with recurrent primary central nervous system tumors was conducted.
      RESULTS: Thirty-six patients were accrued to the study, of which 28 were
      evaluable for toxicity, the primary end point of the trial. We show that
      lenalidomide can be given safely up to doses of 20 mg/m(2), with the only
      toxicity being a probable increased risk of thromboembolic disease.
      Pharmacokinetic studies reveal good bioavailability, linear kinetics, and no
      effects of enzyme-inducing antiepileptic drugs on the metabolism of lenalidomide.
      No objective radiographic responses were seen in any of the treated patients. In
      the group of 24 patients with recurrent glioblastoma, the median time to tumor
      progression was <2 months and only 12.5% of patients were progression-free at 6
      months. CONCLUSION: Lenalidomide is well tolerated in patients with recurrent
      glioma in doses up to 20 mg/m(2). Treatment may be associated with an increased
      risk of thromboembolic disease. Preliminary data suggest that single agent
      activity may be limited in patients with recurrent glioblastoma at the doses
      evaluated although larger studies will be needed to confirm these observations.

PMID- 18056190
TI  - Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy
      in older patients with high-risk myelodysplastic syndromes and acute myeloid
      leukemia following myelodysplastic syndrome.
AB  - PURPOSE: Promoter hypermethylation of, for example, tumor-suppressor genes, is
      considered to be an important step in cancerogenesis and a negative risk factor
      for survival in patients with myelodysplastic syndromes (MDS); however, its role
      for response to therapy has not been determined. This study was designed to
      assess the effect of methylation status on the outcome of conventional induction
      chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute
      myeloid leukemia following MDS were treated with standard doses of daunorubicin
      and 1-beta-d-arabinofuranosylcytosine. Standard prognostic variables and
      methylation status of the P15(ink4b) (P15), E-cadherin (CDH), and hypermethylated
      in cancer 1 (HIC) genes were analyzed before treatment. RESULTS: Forty percent of
      the patients achieved complete remission (CR). CR rate was lower in patients with
      high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P =
      0.02). Whereas P15 status alone was not significantly associated with CR rate (P
      = 0.25), no patient with hypermethylation of all three genes achieved CR (P =
      0.03). Moreover, patients with CDH methylation showed a significantly lower CR
      rate (P = 0.008), and CDH methylation retained its prognostic value also in the
      multivariate analysis. Hypermethylation was associated with increased CD34
      expression, but not with other known predictive factors for response, such as
      cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect
      of methylation status on the outcome of conventional chemotherapy in high-risk
      MDS and acute myelogenous leukemia following MDS. Provided confirmed in an
      independent study, our results should be used as a basis for therapeutic decision
      making in this patient group.

PMID- 18056191
TI  - Phase I evaluation of CDP791, a PEGylated di-Fab' conjugate that binds vascular
      endothelial growth factor receptor 2.
AB  - PURPOSE: Specific blocking of vascular endothelial growth factor receptor 2
      (VEGFR-2) is a novel therapeutic approach. Here, we report the first phase I
      clinical trial evaluation of CDP791, a PEGylated di-Fab' conjugate that binds
      VEGFR-2. EXPERIMENTAL DESIGN: Cohorts of patients received CDP791 at doses
      between 0.3 and 30 mg/kg every 3 weeks for the initial two doses. RESULTS: The
      compound was well tolerated with no dose-limiting toxicity. Dose-related
      hypertension was observed in patients receiving CDP791 10 mg/kg or more and
      several patients on the higher doses developed infusion-related cutaneous
      hemangiomata arising 28 to 106 days after the first drug administration and
      resolving 3 weeks after cessation. Biopsy and histologic evaluation showed that
      CDP791-bound VEGFR-2 is non-phosphorylated, suggesting that the drug is
      biologically active. Concentrations of CDP791 considered biologically relevant
      were sustained for 3 weeks when doses of 10 mg/kg or more were administered.
      Although no reductions in vascular permeability were recorded using dynamic
      contrast enhanced magnetic resonance imaging (DCE-MRI), there was a significant
      dose level-related reduction in tumor growth. While challenging the recent dogma
      that active VEGF inhibitors should modulate DCE-MRI measurements of vascular
      permeability, this highlights the potential of serial three-dimensional tumor
      measurements to detect tumor growth arrest. Twelve patients received drug for
      more than two treatments, although no partial or complete responses were seen.
      CONCLUSION: The data show that CDP791 is biologically active and well tolerated,
      achieving appropriate plasma concentrations when administered at 10 mg/kg or more
      every 3 weeks.

PMID- 18056192
TI  - First in human phase I trial of 852A, a novel systemic toll-like receptor 7
      agonist, to activate innate immune responses in patients with advanced cancer.
AB  - PURPOSE: Recent advances in the understanding of innate immunity suggest that an
      orchestrated sequence of events is required to elicit a productive immune
      response against cancer. We studied the systemic administration of the Toll-like
      receptor 7 agonist 852A, a small-molecule imidazoquinoline, in patients with
      advanced cancer. Preclinical studies showed that 852A stimulates plasmacytoid
      dendritic cells to produce multiple cytokines, such as IFN-alpha, interleukin-1
      receptor antagonist, and IFN-inducible protein-10. Our goal was to define the
      tolerated dose, pharmacokinetics, pharmacodynamics, and immunologic effects of
      852A in humans. EXPERIMENTAL DESIGN: Eligible adult patients with refractory
      solid organ tumors received i.v. 852A thrice weekly for 2 weeks. Patients who had
      responses or stable disease were eligible for additional cycles. RESULTS: Twenty
      five patients (median age, 55.0 years; 72% male) were enrolled in six cohorts at
      dose levels of 0.15 to 2.0 mg/m(2). Serum drug levels showed dose proportionality
      and no evidence of drug accumulation. The maximum tolerated dose was 1.2 mg/m(2);
      higher doses were limited by fatigue and constitutional symptoms. Increases in
      IFN-alpha, interleukin-1 receptor antagonist, and IFN-inducible protein-10,
      immunologic activity, and clinical symptoms were observed in all patients
      receiving dose levels > or =0.6 mg/m(2). Significant correlations were found
      between pharmacodynamic biomarkers and pharmacokinetic variables, and an
      objective clinical response was seen. CONCLUSIONS: 852A was safely administered
      i.v. at doses up to 1.2 mg/m(2) thrice weekly for 2 weeks with transient or
      reversible adverse effects. This novel Toll-like receptor 7 agonist is
      biologically active and holds promise for stimulating innate immune responses.
      Future trials are warranted to assess its therapeutic role in patients with
      cancer.

PMID- 18056193
TI  - Lack of association of single-nucleotide polymorphisms in pregnane X receptor,
      hepatic nuclear factor 4alpha, and constitutive androstane receptor with
      docetaxel pharmacokinetics.
AB  - PURPOSE: This study aims to describe a population pharmacokinetic model for
      docetaxel in Asian breast cancer patients and to evaluate the effects of single
      nucleotide polymorphisms (SNP) in the cytochrome P450 3A (CYP3A) gene expression
      regulators, constitutive androstane receptor (CAR), pregnane X receptor (PXR),
      and hepatic nuclear factor 4alpha (HNF4alpha), on the pharmacokinetics of
      docetaxel. EXPERIMENTAL DESIGN: Docetaxel was given as an i.v. infusion of 75
      mg/m(2) over 1 h to 101 female breast cancer patients. CAR, PXR, and HNF4alpha
      were comprehensively sequenced. Docetaxel concentrations were measured using a
      liquid chromatography/tandem mass spectrometry method and its population
      pharmacokinetic variables, and the covariate effects of clearance predictors were
      estimated using a nonlinear mixed effects model. RESULTS: Final estimates for
      docetaxel clearance was 47.1 L/h/70 kg/1.75 m. Between subject variability in
      docetaxel clearance was 22.5%. Covariates that showed significant association
      with docetaxel clearance included body size, alpha1 acid glycoprotein and liver
      function. SNPs identified in the coding regions of CAR and HNF4alpha and 5'
      untranslated region of PXR in this Asian breast cancer cohort did not seem to
      improve predictability of docetaxel clearance. CONCLUSIONS: SNPs identified in
      CYP3A gene expression regulators CAR, HNF4alpha, and PXR in the Asian female
      breast cancer population do not seem to have any significant effect on the
      clearance of docetaxel, a CYP3A substrate.

PMID- 18056194
TI  - Phase I study of temozolomide and irinotecan for recurrent malignant gliomas in
      patients receiving enzyme-inducing antiepileptic drugs: a north american brain
      tumor consortium study.
AB  - PURPOSE: To determine the maximum tolerated dose of irinotecan when administrated
      with temozolomide every 28 days, in patients with recurrent malignant glioma who
      were also receiving CYP450 enzyme-inducing antiepileptic drugs (EIAED), and to
      characterize the pharmacokinetics of irinotecan and its metabolites. The study
      was also intended to assess whether temozolomide affects the conversion of
      irinotecan to SN-38. DESIGN: Patients with recurrent malignant glioma received a
      fixed dose of temozolomide (150 mg/m(2)) daily for 5 days from days 1 to 5 every
      28 days, and an i.v. infusion of irinotecan on days 1 and 15 of each cycle. The
      starting dose of irinotecan was 350 mg/m(2), which was escalated to 550 mg/m(2)
      in 50-mg/m(2) increments. The plasma pharmacokinetics of irinotecan and its
      active metabolite, SN-38, were determined during the infusion of irinotecan on
      cycle 1, day 1. RESULTS: Thirty-three patients were enrolled into the study and
      treated. Thirty-one patients were evaluable for both tumor response and toxicity
      and two patients were evaluable for toxicity only. Common toxicities included
      neutropenia and thrombocytopenia, nausea, vomiting, and diarrhea. Dose-limiting
      toxicities were grade 3 diarrhea and nausea/vomiting. The maximum tolerated dose
      for irinotecan was determined to be 500 mg/m(2). CONCLUSIONS: The recommended
      phase II dose of irinotecan in combination with temozolomide for patients
      receiving EIAEDs is 500 mg/m(2), administrated every 15 days on a 28-day
      schedule. This study also confirmed that concomitant administration of EIAEDs
      increases irinotecan clearance and influences SN-38 disposition. No
      pharmacokinetic interaction was observed between temozolomide and irinotecan.

PMID- 18056195
TI  - Nutritional modulation of antitumor efficacy and diarrhea toxicity related to
      irinotecan chemotherapy in rats bearing the ward colon tumor.
AB  - PURPOSE: To evaluate and compare the influence of dietary elements on cancer
      progression, chemotherapy efficacy, and toxicity, particularly severe, late-onset
      diarrhea related to irinotecan (CPT-11) treatment. EXPERIMENTAL DESIGN: We used
      laboratory rats fed a standardized basal diet, Ward colon tumor, and CPT-11
      therapy for the study of CPT-11-induced diarrhea. Dietary interventions were
      selected from nutrients already established to modify other forms of colitis and
      which have been hypothesized to mitigate chemotherapy-induced gastrointestinal
      injury (glutamine, n-3 fatty acids, prebiotic oligosaccharides). Animals adapted
      to test diets were treated with CPT-11 at the maximum tolerated dose (125 mg/kg x
      3 days) and diarrhea was followed continuously for 1 week. RESULTS: The inclusion
      of n-3 fatty acids in the diet (5%, w/w of total fat) suppressed tumor growth and
      enhanced CPT-11's efficacy; this treatment did not affect the incidence or
      severity of diarrhea. By contrast, oral glutamine bolus (0.75 g/kg) administered
      prior to each CPT-11 treatment reduced the incidence of severe diarrhea (34.1 +/-
      4.7% versus 53.8 +/- 4.2%, P < 0.005) and decreased the area under the curve of
      diarrhea score (16.5 +/- 1.0 versus 18.8 +/- 0.5, P < 0.05). Identical results
      were obtained with i.v. bolus glutamine administration. Glutamine treatment did
      not alter CPT-11's antitumor efficacy. The addition of prebiotic oligosaccharides
      to the diet (8%, w/w of diet) did not mitigate the severity of diarrhea, and it
      raised the activity of beta-glucuronidase in cecal contents, a key bacterial
      enzyme mediating CPT-11-related intestinal toxicity. CONCLUSION: Our experiments
      suggest that glutamine and n-3 fatty acids might be potentially useful adjuncts
      to CPT-11 treatment.

PMID- 18056196
TI  - Combination of measles virus virotherapy and radiation therapy has synergistic
      activity in the treatment of glioblastoma multiforme.
AB  - PURPOSE: Glioblastoma multiforme is the most frequent primary brain tumor in
      adults and represents one of the most lethal malignancies with a median survival
      of 12-16 months. We have previously shown that an oncolytic measles virus
      derivative expressing soluble human carcinoembryonic antigen (MV-CEA) has
      significant antitumor activity against glioblastoma multiforme cell lines and
      xenografts. Radiation therapy (RT) represents one of the mainstays of glioma
      treatment. Here we tested the hypothesis that the combination of RT with MV-CEA
      would have synergistic activity against gliomas. EXPERIMENTAL DESIGN: 3-(4,5
      Dimethyl-thiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      (MTS) and clonogenic assays were used to test cytoxicity of the combination
      treatment in vivo. To examine the mechanism of synergy, one-step viral growth
      curves, terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling
      (TUNEL) assays, and Western blot analyses were performed. In vivo assessment of
      synergistic antitumor activity was conducted in a U87 glioma model. RESULTS: MTS
      and clonogenic assays showed a strong synergistic interaction between MV-CEA and
      RT in glioblastoma multiforme cells including both primary and established glioma
      lines. Furthermore, significant antitumor efficacy was observed in vivo in a
      subcuteneous U87 xenograph model. There was significant prolongation of survival
      (P = 0.001) in the combination treatment group as compared with single modality-
      or control-treated animals. One-step viral growth curves showed increased viral
      burst size by up to 2 log in MV/RT combination-treated cells, as compared with
      single agent MV-CEA-treated glioma cells. Changes in CEA levels and expression of
      viral N and H protein were also consistent with increased viral production.
      Furthermore, TUNEL assays and Western blot analysis showed increase in apoptosis
      in MV/RT combination-treated cells. The pan-caspase inhibitor Z-VAD-FMK and the
      caspase-8 inhibitor Z-IETD-FMK, but not the caspase-9 inhibitor Z-IEHD-FMK,
      protected glioma cells from MV-CEA/RT-induced cleavage of poly(ADP-ribose)
      polymerase (PARP), indicating that the apoptotic death in combination-treated
      cells is mostly mediated via the extrinsic caspase pathway. The Fas/Fas ligand
      interaction blocking antibody NOK-1 blocked MV/RT-induced PARP cleavage whereas
      the Fas agonistic antibody CH11 increased PARP cleavage in MV/RT combination
      treated cells. Reverse transcription-PCR, fluorescence-activated cell sorting
      analysis and immunohistochemistry showed up-regulation of Fas in combination
      treated tumor in vitro and in vivo cells. CONCLUSIONS: There is synergy between
      MV-CEA and RT in vitro and in vivo. The synergistic effect of the combination
      seems to be due to increase in viral burst size and increase in apoptotic cell
      death. This latter effect is mostly mediated via the extrinsic caspase-8 pathway,
      activated via increased signaling through the Fas death receptor pathway. These
      results could have translational implications in glioma therapy.

PMID- 18056197
TI  - Anti-mesothelin immunotoxin SS1P in combination with gemcitabine results in
      increased activity against mesothelin-expressing tumor xenografts.
AB  - PURPOSE: To determine the antitumor activity of the anti-mesothelin immunotoxin
      SS1P in combination with gemcitabine against mesothelin-expressing tumor
      xenografts. EXPERIMENTAL DESIGN: The in vitro activity of SS1P in combination
      with gemcitabine against the mesothelin-expressing cell line A431/K5 was
      evaluated using cytotoxicity and apoptosis assays. The antitumor activity of this
      combination was evaluated in nude mice bearing A431/K5 tumor xenografts. Tumor
      bearing mice were treated with different doses and schedules of gemcitabine
      alone, SS1P alone (0.2 mg/kg i.v. every other day x three doses), or with both
      agents together, and tumor volumes were measured over time. RESULTS: In vitro
      studies failed to show the synergy of SS1P plus gemcitabine against the
      mesothelin-expressing A431/K5 cells. In contrast, in the in vivo setting, there
      was a marked synergy when SS1P was combined with gemcitabine for the treatment of
      mesothelin-expressing tumor xenografts. This synergy was present using different
      doses and schedules of gemcitabine administration. In mice treated with
      fractionated doses of gemcitabine in combination with SS1P, complete tumor
      regression was observed in all mice and was long-lasting in 60% of the animals.
      Also, this antitumor activity was specific to SS1P because HA22, an immunotoxin
      targeting CD22 not expressed on A431/K5 cells, did not increase the efficacy of
      gemcitabine. CONCLUSIONS: SS1P in combination with gemcitabine results in marked
      antitumor activity against mesothelin-expressing tumors. This combination could
      be potentially useful for the treatment of human cancers that express mesothelin
      and are responsive to gemcitabine therapy.

PMID- 18056198
TI  - CD8+ T cells induce complete regression of advanced ovarian cancers by an
      interleukin (IL)-2/IL-15 dependent mechanism.
AB  - PURPOSE: In vitro studies suggest that ovarian cancer evades immune rejection by
      fostering an immunosuppressive environment within the peritoneum; however, the
      functional responses of ovarian cancer-specific T cells have not been directly
      investigated in vivo. Therefore, we developed a new murine model to enable
      tracking of tumor-specific CD8(+) T-cell responses to advanced ovarian tumors.
      EXPERIMENTAL DESIGN: The ovarian tumor cell line ID8 was transfected to stably
      express an epitope-tagged version of HER-2/neu (designated Neu(OT-I/OT-II)).
      After i.p. injection into C57BL/6 mice, ID8 cells expressing Neu(OT-I/OT-II) gave
      rise to disseminated serous adenocarcinomas with extensive ascites. CD8(+) T
      cells expressing a transgenic T-cell receptor specific for the OT-I epitope of
      Neu(OT-I/OT-II) were adoptively transferred into tumor-bearing mice, and
      functional responses were monitored. Cytokine signaling requirements were
      evaluated by comparing the responses of wild-type donor T cells with those with
      genetic deletion of the interleukin (IL)-2/IL-15 receptor beta subunit (CD122) or
      the IL-2 receptor alpha subunit (CD25). RESULTS: On adoptive transfer into tumor
      bearing hosts, wild-type OT-I T cells underwent a striking proliferative
      response, reaching peak densities of approximately 40% and approximately 90% of
      CD8(+) T cells in peripheral blood and ascites, respectively. OT-I cells
      infiltrated and destroyed tumor tissue, and ascites completely resolved within 10
      days. By contrast, CD122(-/-) OT-I cells and CD25(-/-) OT-I cells proliferated in
      blood but failed to accumulate in ascites or tumor tissue or induce tumor
      regression. CONCLUSIONS: Contrary to expectation, advanced ovarian cancers can
      support extraordinary CD8(+) T-cell proliferation and antitumor activity through
      an IL-2/IL-15-dependent mechanism.

PMID- 18056199
TI  - Low-dose 12-O-tetradecanoylphorbol-13-acetate enhances tumor necrosis factor
      related apoptosis-inducing ligand induced apoptosis in prostate cancer cells.
AB  - PURPOSE: Previously, we have shown that c-Fos/activator protein-1 (AP-1) promotes
      tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced
      apoptosis by repressing the antiapoptotic molecule c-FLIP(L). In this study, we
      investigated whether synthetic induction of c-Fos/AP-1 by 12-O
      tetradecanoylphorbol-13-acetate (TPA) converts the phenotype of TRAIL-resistant
      prostate cancer cells to a TRAIL-sensitive phenotype in vitro and in vivo.
      EXPERIMENTAL DESIGN: Low-dose TPA was used to determine whether LNCaP prostate
      cancer cells could be converted to a TRAIL-sensitive phenotype in in vitro and in
      vivo studies. We also assessed whether TPA enhancement of TRAIL-induced apoptosis
      varies between androgen-sensitive and androgen-insensitive prostate cancer cells
      and evaluated the role of TRAIL receptors, DR4 and DR5, in TPA-enhanced TRAIL
      induced apoptosis. RESULTS: We show that the combination of TRAIL with low-dose
      TPA has no effect on nonmalignant prostate epithelial cells; however, TPA up
      regulates most AP-1 proteins and AP-1 activity, reduces c-FLIP(L), and
      potentiates TRAIL-induced apoptosis. We show that the combination of TPA + TRAIL
      is effective in promoting apoptosis in both hormone-sensitive LNCaP and hormone
      insensitive LNCaP-C4-2 prostate cancer cells. Although TPA enhances the TRAIL
      receptor 1 (DR4) level, sensitization of prostate cancer cells seems to be more
      dependent on TRAIL-receptor 2 (DR5) than TRAIL-receptor 1 levels. In vivo
      xenograft experiments suggest that TPA elevates the expression of c-Fos and
      reduces c-FLIP(L). Combination of TPA with TRAIL-receptor 2 agonist antibody,
      lexatumumab, effectively increases apoptosis and reduces LNCaP xenograft tumor
      burden. CONCLUSIONS: TPA, when combined with the proapoptotic agent TRAIL, is
      effective in changing the phenotype of some TRAIL-resistant prostate cancer cells
      to a TRAIL-sensitive phenotype.

PMID- 18056200
TI  - The Bcl-2/Bcl-XL family inhibitor ABT-737 sensitizes ovarian cancer cells to
      carboplatin.
AB  - PURPOSE: The effective treatment of ovarian cancer is hampered by the development
      of drug resistance, which may be mediated by members of the Bcl-2 family of
      apoptosis regulators. ABT-737 is a recently described inhibitor of members of
      this family. We investigated whether this compound could sensitize ovarian cancer
      cells to chemotherapeutic agents. EXPERIMENTAL DESIGN: The sensitivity of ovarian
      cancer cell lines to ABT-737 in combination with either carboplatin or paclitaxel
      was tested either in vitro by assessing cell growth/survival and apoptosis or in
      xenograft studies. RESULTS: As a single agent, ABT-737 inhibited the growth of
      eight ovarian cancer cell lines, although with relatively poor potency. However,
      ABT-737, but not a less active enantiomer, increased the sensitivity of several
      cell lines to carboplatin. The increased sensitivity to carboplatin was
      accompanied by a decrease in time at which apoptosis was observed when assessed
      according to the number of attached cells, PARP cleavage, and nucleosome
      formation. ABT-737 was more effective at sensitizing IGROV-1 cells when ABT-737
      was administered after carboplatin. In addition, ABT-737 significantly enhanced
      the activity of carboplatin in one of three primary cultures derived directly
      from ascitic tumor cells in patients recently treated with chemotherapy. Small
      interfering RNA directed to Bcl-X(L) also increased the sensitivity of ovarian
      cancer cell lines to carboplatin. ABT-737 was also able to augment the inhibition
      of IGROV-1 tumor xenograft growth beyond that obtained with carboplatin alone.
      CONCLUSIONS: These data suggest that ABT-737, in combination with carboplatin,
      may find utility in the treatment of patients with ovarian cancer.

PMID- 18056201
TI  - Alteration of cellular and humoral immunity by mutant p53 protein and processed
      mutant peptide in head and neck cancer.
AB  - PURPOSE: To determine if serologic recognition of p53 mutations at the protein
      level depends upon the ability of mutant p53 to express new peptide epitopes that
      bind to human leukocyte antigen (HLA) class II molecules, we used anti-p53
      antibody production as a marker for HLA class II-restricted T-cell involvement in
      head and neck cancer. EXPERIMENTAL DESIGN: An anti-p53 antibody response was
      correlated with specific p53 mutations and the patients' HLA class II alleles and
      haplotypes. HLA binding studies and in vitro stimulation (IVS) of peripheral
      blood mononuclear cells were done using a mutant versus wild-type HLA-DQ7-binding
      p53 peptide. RESULTS: Certain HLA-DQ and HLA-DR alleles were frequently present
      in p53 seropositive patients who produced serum anti-p53 antibodies. Selected
      mutated p53 peptides fit published allele-specific HLA class II binding motifs
      for the HLA-DQ7 or HLA-DR1 molecules. Moreover, a mutant p53 peptide bound with a
      10-fold greater affinity than the wild-type p53 peptide to HLA-DQ7 molecules. IVS
      of CD4(+) T cells from seven healthy HLA-DQ7(+) donors using this mutant p53
      peptide (p53(220C)) was associated with a partial T helper type 2 phenotype
      compared with IVS using the wild-type p53(210-223) peptide. CONCLUSIONS: Our
      results support the hypothesis that mutated p53 neoantigens can bind to specific
      HLA class II molecules, leading to a break in tolerance. This may lead to skewing
      of the CD4(+) T lymphocyte response toward a tumor-permissive T helper type 2
      profile in head and neck cancer patients, as manifested by seropositivity for
      p53.

PMID- 18056202
TI  - Glutathione S-transferase T1 and M1: gene sequence variation and functional
      genomics.
AB  - PURPOSE: The glutathione S-transferases (GSTs) catalyze the glutathione
      conjugation of reactive electrophiles, including carcinogens and many
      antineoplastic drugs. GSTT1 and GSTM1 are polymorphically deleted, but the full
      range of genetic variation in these two genes has not yet been explored. We set
      out to systematically identify common polymorphisms in GSTT1 and GSTM1, followed
      by functional genomic studies. EXPERIMENTAL DESIGN: First, multiplex PCR was used
      to determine GSTT1 and GSTM1 copy number in 400 DNA samples (100 each from 4
      ethnic groups). Exons, splice junctions, and 5'-flanking regions (5'-FR) were
      then resequenced using DNA samples that contained at least one copy of GSTT1 or
      GSTM1. RESULTS: Gene deletion frequencies among ethnic groups were from 33.5% to
      73.5% for GSTT1 and from 50.5% to 78.0% for GSTM1. GSTT1 deletion data correlated
      with the results of mRNA microarray expression studies. The 18 single nucleotide
      polymorphisms (SNP) observed in GSTT1 included three nonsynonymous coding SNPs
      (cSNPs) and one single-nucleotide deletion, whereas the 51 GSTM1 SNPs included
      two nonsynonymous cSNPs. Two of the GSTT1 nonsynonymous cSNPs resulted in
      decreases in levels of immunoreactive protein to 56% and 12% of wild type (WT),
      whereas those in GSTM1 resulted in modest increases in protein levels. Reporter
      gene assays showed that one GSTT1 5'-FR haplotype, with a frequency of 32% in
      African-American subjects, resulted in an increase in transcription in JEG-3
      cells to 351% of that for the WT sequence, and one GSTM1 5'-FR haplotype resulted
      in an increase in transcription in JEG-3 cells to 129% of WT. CONCLUSIONS: These
      observations suggest that functionally significant pharmacogenomic variation
      beyond GSTT1 and GSTM1 gene deletion may contribute to carcinogenesis or
      individual variation in antineoplastic drug therapy response.

PMID- 18056203
TI  - Plasma, tumor, and tissue disposition of STEALTH liposomal CKD-602 (S-CKD602) and
      nonliposomal CKD-602 in mice bearing A375 human melanoma xenografts.
AB  - PURPOSE: S-CKD602 is a STEALTH liposomal formulation of CKD-602, a camptothecin
      analogue. The cytotoxicity of camptothecin analogues is related to the duration
      of exposure in the tumor. STEALTH liposomal formulations contain lipid conjugated
      to methoxypolyethylene glycol and have been designed to prolong drug circulation
      time, increase tumor delivery, and improve the therapeutic index. For STEALTH
      liposomal formulations of anticancer agents to achieve antitumor effects, the
      active drug must be released into the tumor extracellular fluid (ECF).
      EXPERIMENTAL DESIGN: S-CKD602 at 1 mg/kg or nonliposomal CKD-602 at 30 mg/kg was
      administered once via tail vein to mice bearing A375 human melanoma xenografts.
      Mice (n = 3 per time point) were euthanized at 0.083 to 24 h, 48 h, and 72 h
      after S-CKD02 and from 0.083 to 24 h after nonliposomal CKD-602. Plasma samples
      were processed to measure encapsulated, released, and sum total (encapsulated
      plus released) CKD-602, and tumor and tissue samples were processed to measure
      sum total CKD-602. Microdialysis samples of tumor ECF were obtained from 0 to 2
      h, 4 to 7 h, and 20 to 24 h after nonliposomal CKD-602 and from 0 to 2 h, 24 to
      27 h, 48 to 51 h, and 72 to 75 h after S-CKD602. A liquid chromatography-mass
      spectrometry assay was used to measure the total (sum of lactone and hydroxyl
      acid) CKD-602. The area under the concentration-versus-time curves (AUC) from 0
      to infinity and time >1 ng/mL in tumor were estimated. RESULTS: For S-CKD602, the
      CKD-602 sum total AUC in plasma and tumor and the CKD-602 AUC in tumor ECF were
      201,929, 13,194, and 187 ng/mL h, respectively. For S-CKD602, 82% of CKD-602
      remains encapsulated in plasma. For nonliposomal CKD-602, the CKD-602 AUC in
      plasma and tumor and the CKD-602 AUC in tumor ECF were 9,117, 11,661, and 639
      ng/mL.h, respectively. The duration of time the CKD-602 concentration was >1
      ng/mL in tumor ECF after S-CKD602 and nonliposomal CKD-602 was >72 and
      approximately 20 h, respectively. For S-CKD602, the CKD-602 sum total exposure
      was 1.3-fold higher in fat as compared with muscle. The ratio of CKD-602 sum
      total exposure in fat to muscle was 3.8-fold higher after administration of S
      CKD602 compared with nonliposomal CKD-602. CONCLUSION: S-CKD602 provides
      pharmacokinetic advantages in plasma, tumor, and tumor ECF compared with
      nonliposomal CKD-602 at 1/30th of the dose, which is consistent with the improved
      antitumor efficacy of S-CKD602 in preclinical studies. The distribution of S
      CKD602 is greater in fat compared with muscle whereas the distribution of
      nonliposomal CKD-602 is greater in muscle compared with fat. These results
      suggest that the body composition of a patient may affect the disposition of S
      CKD602 and released CKD-602.

PMID- 18056204
TI  - Tomorrow and tomorrow and tomorrow: wait times for multidisciplinary pain clinics
      in Canada.

PMID- 18056205
TI  - Mechanisms of opioid tolerance: merging evidence and therapeutic implications.

PMID- 18056206
TI  - Challenges in accessing multidisciplinary pain treatment facilities in Canada.
AB  - PURPOSE: The objective of this survey was to examine the services offered by
      multidisciplinary pain treatment facilities (MPTFs) across Canada and to compare
      access to care at these MPTFs. METHODS: A MPTF was defined as a clinic that
      advertised specialized multidisciplinary services for the diagnosis and
      management of patients with chronic pain, having a minimum of three different
      health care disciplines (including at least one medical speciality) available and
      integrated within the facility. The search method included approaching all
      hospital and rehabilitation centre administrators in Canada, the Insurance Bureau
      of Canada, the Workplace Safety and Insurance Board or similar body in each
      province. Designated investigators were responsible for confirming and
      supplementing MPTFs from the preliminary list for each province. Administrative
      leads at each eligible MPTF were asked to complete a detailed questionnaire
      regarding their MPTF infrastructure, clinical, research, teaching and
      administrative activities. RESULTS: Completed survey forms were received from 102
      MPTFs (response rate 85%) with 80% concentrated in major cities, and none in
      Prince Edward Island and the Territories. The MPTFs offer a wide variety of
      treatments including non-pharmacological modalities such as interventional,
      physical and psychological therapy. The median wait time for a first appointment
      in public MPTFs is six months, which is approximately 12 times longer than non
      public MPTFs. Eighteen pain fellowship programs exist in Canadian MPTFs and 64%
      engage in some form of research activities CONCLUSION: Canadian MPTFs are unable
      to meet clinical demands of patients suffering from chronic pain, both in terms
      of regional accessibility and reasonable wait time for patients' first
      appointment.

PMID- 18056207
TI  - Dedicated multidisciplinary pain management centres for children in Canada: the
      current status.
AB  - PURPOSE: The objective of this study was to examine the services currently
      offered by multidisciplinary pain treatment facilities (MPTFs) dedicated for
      pediatric chronic pain management across Canada. METHODS: A MPTF was defined as a
      clinic that advertised specialized multidisciplinary services for the diagnosis
      and management of chronic pain and had a minimum of three different health care
      disciplines (including at least one medical speciality) available and integrated
      within the facility. The search method was previously described in an
      accompanying article. Designated investigators were responsible for confirming
      and supplementing MPTFs from the preliminary list in their respective provinces.
      Administrative leads at each eligible MPTF were asked to complete a detailed
      questionnaire on their infrastructure, clinical, research, teaching and
      administrative activities. Only MPTFs dedicated to pediatric populations were
      included. RESULTS: Only five centres surveyed had dedicated pediatric MPTFs, all
      located in major cities in five different provinces. While the median wait time
      was four weeks, it could be as long as nine months in one MPTF. Headache and
      neuropathic pain were the most commonly treated pain syndromes. All MPTFs
      included physicians, nurses and psychologists, and used a rehabilitation model
      that incorporated a wide variety of pharmacological, psychological and physical
      therapies. All centres provided training for medical and other healthcare
      professionals, and three of the five centres conducted research. Government
      funding was the major source of funding for patient services and overhead costs.
      CONCLUSIONS: There are very few pediatric MPTFs in Canada. These facilities exist
      in five of ten provinces, each within large urban centres. Limited accessibility
      leads to variable and prolonged wait times for pediatric patients suffering from
      chronic pain.

PMID- 18056208
TI  - Simulation performance checklist generation using the Delphi technique.
AB  - PURPOSE: Performance assessment using high fidelity simulation is problematic,
      due to the difficulty in developing valid and reliable evaluation tools. The
      Delphi technique is a consensus based content generation method used for multiple
      purposes such as policy development, best-evidence practice guidelines and
      competency assessments. The purpose of this study was to develop checklists using
      a modified Delphi technique to evaluate the performance of practicing
      anesthesiologists managing two simulated scenarios. METHODS: The templates for
      two simulation scenarios were emailed to five anesthesiologists who were asked to
      generate performance items. Data were collated anonymously and returned. An a
      priori decision was made to delete items endorsed by </= 20% of participants.
      This process of collection, collation and re-evaluation was repeated until
      consensus was reached. Four independent raters used the checklist to assess three
      subjects managing the two simulation scenarios. Interrater reliability was
      assessed using average measures intraclass correlation (ICC) and repeated
      measures analysis of variance (ANOVA) was used to assess differences in
      difficulty between scenarios. RESULTS: The final checklists included 131 items
      for scenario 1 and 126 items for scenario 2. The mean inter-rater reliability was
      0.921 for scenario 1 and 0.903 for scenario 2. Repeated measures ANOVA revealed
      no statistically significant difference in difficulty between scenarios.
      DISCUSSION: The Delphi technique can be very useful to generate consensus based
      evaluation tools with high content and face validity compared to subjective
      evaluative tools. Since there was no difference in scenario difficulty, these
      scenarios can be used to determine the effect of educational interventions on
      performance.

PMID- 18056209
TI  - MK-801 enhances gabaculine-induced loss of the righting reflex in mice, but not
      immobility.
AB  - PURPOSE: gamma-Aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptors
      are important targets for anesthetic action at the in vitro cellular level.
      Gabaculine is a GABA-trans-aminase inhibitor that increases endogenous GABA in
      the brain, and enhances GABA activity. We have recently shown that
      unconsciousness is associated with the enhanced GABA activity due to gabaculine,
      but that immobility is not. MK-801 is a selective NMDA channel blocker. In this
      study, we examined behaviourally whether gabaculine in combination with MK-801
      could produce these components of the general anesthetic state. We further
      compared the effect of MK-801 with ketamine, another NMDA channel blocker.
      METHODS: All drugs were administered intraperitoneally to adult male ddY mice. To
      assess the general anesthetic components, two endpoints were used. One was loss
      of the righting reflex (LORR; as a measure of unconsciousness) and the other was
      loss of movement in response to tail-clamp stimulation (as a measure of
      immobility). RESULTS: Large doses of MK-801 alone (10-50 mg.kg(-1)) induced
      neither LORR nor immobility in response to noxious stimulation. However, even a
      small dose (0.2 mgxkg(-1)) significantly enhanced gabaculine-induced LORR (P <
      0.05), although gabaculine in combination with MK-801 (0.2-10 mgxkg(-1)) produced
      no immobility. However, gabaculine plus a subanesthetic dose of ketamine (30
      mgxkg(-1)), which acts on NMDA, opioid and nicotinic acetylcholine receptors and
      neuronal Na(+) channels, suppressed the pain response, but did not achieve a full
      effect. Ketamine alone dose-dependently produced both LORR and immobility.
      CONCLUSION: These findings suggest that gabaculine-induced LORR is modulated by
      blocking NMDA receptors, but that immobility is not mediated through GABA or NMDA
      receptors.

PMID- 18056210
TI  - Case series: Septa can influence local anesthetic spread during infraclavicular
      brachial plexus blocks.
AB  - PURPOSE: To ultrasonically identify the presence of septae within the
      neurovascular sheath and to assess their effect on local anesthetic spread when
      performing infraclavicular brachial plexus blocks. CLINICAL FEATURES: Thirty ASA
      status I and II patients scheduled for minor hand surgeries were enrolled in the
      study. Ultrasound guided infraclavicular brachial plexus blocks were performed on
      28 patients. The images of the local anesthetic spread and the effect of the
      septum within the neurovascular sheath were analyzed. Septae were present in four
      of six patients where unilateral local anesthetic spread was seen. Septae were
      not visualized in the 22 patients with unrestricted local anesthetic spread after
      the initial injection. All 28 patients underwent their planned operations
      successfully with adequate anesthesia. CONCLUSIONS: Our study shows that the
      presence of septae within the neurovascular sheath may influence the pattern of
      local anesthetic spread associated with the infraclavicular approach to brachial
      plexus blocks.

PMID- 18056211
TI  - Case report: transfusion-related acute lung injury (TRALI) - a clear and present
      danger.
AB  - PURPOSE: To describe a case of transfusion-related acute lung injury (TRALI)
      after platelet transfusion immediately following cardiac surgery, and to review
      the clinical features, pathophysiology, management, and morbidity and mortality
      associated with such an event. CLINICAL FEATURES: A 62-yr-old man was transferred
      to our centre for urgent coronary artery bypass grafting in the setting of recent
      anti-platelet medication use. Soon after surgery he received platelet
      transfusions despite having only moderate blood loss. Shortly following the
      platelet transfusion, he suffered acute hypoxic and hypotensive decompensation
      requiring nitric oxide therapy, inotropic support, and prolonged need for
      mechanical ventilation. The patient was eventually discharged from the intensive
      care unit nine days following the event. The diagnosis of TRALI was made by
      clinical and radiographic criteria. CONCLUSION: Transfusion-related acute lung
      injury is now the leading cause of transfusion-related fatalities. Early
      diagnosis of TRALI is important and these reactions should be reported to the
      blood transfusion service so that appropriate action can be taken to prevent
      future morbidity and mortality in other patients. To reduce serious transfusion
      reactions, inappropriate transfusions must be minimized and the decision to
      transfuse blood products should be taken with care.

PMID- 18056212
TI  - Diastolic rotational flow in the aortic arch.

PMID- 18056213
TI  - Left ventricular outflow obstruction in a patient with undiagnosed hypertrophic
      obstructive cardiomyopathy.

PMID- 18056214
TI  - Anesthetic management of pediatric adenotonsillectomy.

PMID- 18056215
TI  - Anesthesiologists and the pharmaceutical industry: awareness is paramount.

PMID- 18056216
TI  - Interference of bispectral index monitoring with intraoperative use of the
      electromyograph endotracheal tube.

PMID- 18056217
TI  - A call to Mallinckrodt for a modified right-sided Broncho-Cath double lumen tube.

PMID- 18056218
TI  - Laryngeal mask airways: proprietary issues.

PMID- 18056219
TI  - Verification of vocal cord function using the Pentax-AirwayScope.

PMID- 18056220
TI  - Recurrent postoperative deep vein thrombosis in a patient with obstructive sleep
      apnea and malignant hyperthermia susceptibility.

PMID- 18056222
TI  - An event-related brain potential study of direct and indirect semantic priming in
      schizophrenia.
AB  - OBJECTIVE: Following a meaningful prime stimulus, schizophrenia patients have
      been hypothesized to exhibit impaired neurophysiological activation of related
      concepts in general, and/or supranormal activation of weakly related concepts in
      particular, within semantic memory. The former abnormality may occur at longer
      intervals, and the latter at shorter intervals, after the prime. The authors
      tested these hypotheses using the N400 event-related brain potential as a probe
      of activation of concepts in semantic memory. METHOD: Event-related potentials
      were recorded in 16 schizophrenia patients and 16 normal comparison subjects who
      viewed prime words, each followed by a target that was a directly (strongly)
      related word, indirectly (weakly) related word, unrelated word, or nonword, in a
      lexical-decision task. Equal numbers of each target type were presented 300 and
      750 msec after the prime. RESULTS: In the comparison subjects, N400 amplitude was
      largest (most negative) following unrelated targets, intermediate after
      indirectly related targets, and smallest after directly related targets. In
      contrast, patients' N400 amplitudes did not differ between these target types,
      reflecting larger amplitudes following both directly and indirectly related
      targets in patients than in comparison subjects; these findings held regardless
      of prime-to-target stimulus-onset asynchrony. Within patients, at the longer
      asynchrony, larger N400 amplitudes after directly and indirectly related targets
      correlated with positive psychotic symptoms. CONCLUSIONS: The results suggest
      hypoactivation of strongly and weakly related concepts following a meaningful
      stimulus, regardless of interval, in schizophrenia. An N400 index of this
      hypoactivation correlated with severity of delusions, suggesting a role for
      abnormal semantic processing in their pathogenesis.

PMID- 18056223
TI  - Infections in the CNS during childhood and the risk of subsequent psychotic
      illness: a cohort study of more than one million Swedish subjects.
AB  - OBJECTIVE: Infections during early life have been suggested to play a role in the
      etiology of schizophrenia. Most studies have focused on fetal life; few have
      explored risk associated with infection during childhood. The results of these
      have been inconsistent. The present study aims to investigate whether there is an
      increased risk of schizophrenia and other nonaffective psychoses associated with
      viral or bacterial CNS infections during childhood and, if so, which specific
      agents are involved. METHOD: A national cohort consisting of 1.2 million children
      born between 1973 and 1985 was followed up by using Swedish national registers to
      retrieve data on hospital admissions for CNS infections at 0-12 years of age
      (bacterial: N=2,435, viral: N=6,550) as well as admissions for nonaffective
      psychotic illnesses from the 14th birthday (N=2,269). RESULTS: There was a
      slightly increased risk of nonaffective psychotic illness associated with viral
      CNS infections, as well as schizophrenia. There was no evidence of increased risk
      in relation to bacterial infections. When divided into specific agents, exposures
      to mumps virus or cytomegalovirus were associated with subsequent psychoses.
      CONCLUSIONS: Serious viral CNS infections during childhood appear to be
      associated with the later development of schizophrenia and nonaffective
      psychoses. The association with specific viruses suggests that the risk is
      related to infectious agents with a propensity to invade the brain parenchyma.

PMID- 18056224
TI  - Acute effect of methadone maintenance dose on brain FMRI response to heroin
      related cues.
AB  - OBJECTIVE: Environmental drug-related cues have been implicated as a cause of
      illicit heroin use during methadone maintenance treatment of heroin dependence.
      The authors sought to identify the functional neuroanatomy of the brain response
      to visual heroin-related stimuli in methadone maintenance patients. METHOD: Event
      related functional magnetic resonance imaging was used to compare brain responses
      to heroin-related stimuli and matched neutral stimuli in 25 patients in methadone
      maintenance treatment. Patients were studied before and after administration of
      their regular daily methadone dose. RESULTS: The heightened responses to heroin
      related stimuli in the insula, amygdala, and hippocampal complex, but not the
      orbitofrontal and ventral anterior cingulate cortices, were acutely reduced after
      administration of the daily methadone dose. CONCLUSIONS: The medial prefrontal
      cortex and the extended limbic system in methadone maintenance patients with a
      history of heroin dependence remains responsive to salient drug cues, which
      suggests a continued vulnerability to relapse. Vulnerability may be highest at
      the end of the 24-hour interdose interval.

PMID- 18056225
TI  - Efficacy of sibutramine for the treatment of binge eating disorder: a randomized
      multicenter placebo-controlled double-blind study.
AB  - OBJECTIVE: Preliminary evidence suggests that the antiobesity agent sibutramine
      is effective in the treatment of binge eating disorder, impacting both binge
      eating and weight. This study is the first large-scale, multisite, placebo
      controlled trial to test the efficacy of sibutramine in binge eating disorder.
      METHOD: Participants (N=304) who met DSM-IV criteria for binge eating disorder
      were randomly assigned to 24 weeks of double-blind sibutramine (15 mg) or placebo
      treatment. The outcome measures included the frequency of eating binges (primary
      outcome), binge day frequency, body mass index, body weight, global improvement,
      response categories, associated eating pathology, and quality of life. The
      primary analysis for continuous measures was the difference between groups in the
      change from baseline to endpoint using analysis of variance (ANOVA) with the last
      observation carried forward. RESULTS: Compared with subjects receiving placebo,
      participants who received sibutramine had a significantly greater reduction in
      weekly binge frequency (sibutramine group mean=2.7 [SD=1.7], placebo group
      mean=2.0 [SD=2.3]); weight loss (sibutramine group mean=4.3 kg [SD=4.8], placebo
      group mean=0.8 kg [SD=3.5]); reduction in frequency of binge days; reduction in
      body mass index; global improvement; level of response, including the percentage
      of abstinence from binge eating (sibutramine group: 58.7%; placebo group: 42.8%);
      and reduction in eating pathology (cognitive restraint, disinhibition, and
      hunger). The change in quality of life scores was not significant. Sibutramine
      was associated with significantly higher incidence of headache, dry mouth,
      constipation, insomnia, and dizziness. CONCLUSIONS: This trial demonstrated the
      efficacy of sibutramine in reducing binge eating, weight, and associated
      psychopathology.

PMID- 18056226
TI  - Bipolar disorder and pregnancy: risks revealed.

PMID- 18056227
TI  - Religion, spirituality, and medicine.

PMID- 18056228
TI  - Brain mechanisms of borderline personality disorder at the intersection of
      cognition, emotion, and the clinic.

PMID- 18056230
TI  - Issues for DSM-V: simplifying DSM-IV to enhance utility: the case of major
      depressive disorder.

PMID- 18056231
TI  - The revised warning for antidepressants and suicidality: unveiling the black box
      of statistical analyses.

PMID- 18056232
TI  - Elucidating the role of brain-derived neurotrophic factor in the brain.

PMID- 18056234
TI  - Anorexia nervosa.

PMID- 18056233
TI  - A meta-analysis of cognitive remediation in schizophrenia.
AB  - OBJECTIVE: This study evaluated the effects of cognitive remediation for
      improving cognitive performance, symptoms, and psychosocial functioning in
      schizophrenia. METHOD: A meta-analysis was conducted of 26 randomized, controlled
      trials of cognitive remediation in schizophrenia including 1,151 patients.
      RESULTS: Cognitive remediation was associated with significant improvements
      across all three outcomes, with a medium effect size for cognitive performance
      (0.41), a slightly lower effect size for psychosocial functioning (0.36), and a
      small effect size for symptoms (0.28). The effects of cognitive remediation on
      psychosocial functioning were significantly stronger in studies that provided
      adjunctive psychiatric rehabilitation than in those that provided cognitive
      remediation alone. CONCLUSIONS: Cognitive remediation produces moderate
      improvements in cognitive performance and, when combined with psychiatric
      rehabilitation, also improves functional outcomes.

PMID- 18056235
TI  - Frontotemporal dementia and mania.

PMID- 18056236
TI  - Risk of recurrence in women with bipolar disorder during pregnancy: prospective
      study of mood stabilizer discontinuation.
AB  - OBJECTIVE: This study estimated the risk of recurrence of mood episodes among
      women with a history of bipolar disorder who continued or discontinued treatment
      with mood stabilizers during pregnancy. METHOD: In a prospective observational
      clinical cohort study, the authors determined recurrence risk and survival
      analysis-based time to recurrence of a new episode in 89 pregnant women with DSM
      IV bipolar disorder. Eligible subjects were euthymic at conception and continued
      mood stabilizer treatment or discontinued treatment proximate to conception.
      RESULTS: The overall risk of at least one recurrence in pregnancy was 71%. Among
      women who discontinued versus continued mood stabilizer treatment, recurrence
      risk was twofold greater, median time to first recurrence was more than fourfold
      shorter, and the proportion of weeks ill during pregnancy was five times greater.
      Median recurrence latency was 11 times shorter after abrupt/rapid versus gradual
      discontinuation of mood stabilizer. Most recurrences were depressive or mixed
      (74%), and 47% occurred during the first trimester. Predictors of recurrence
      included bipolar II disorder diagnosis, earlier onset, more recurrences/year,
      recent illness, use of antidepressants, and use of anticonvulsants versus
      lithium. CONCLUSIONS: Discontinuation of mood stabilizer, particularly abruptly,
      during pregnancy carries a high risk for new morbidity in women with bipolar
      disorder, especially for early depressive and dysphoric states. However, this
      risk is reduced markedly by continued mood stabilizer treatment. Treatment
      planning for pregnant women with bipolar disorder should consider not only the
      relative risks of fetal exposure to mood stabilizers but also the high risk of
      recurrence and morbidity associated with stopping maintenance mood stabilizer
      treatment.

PMID- 18056237
TI  - Religion, spirituality, and medicine: psychiatrists' and other physicians'
      differing observations, interpretations, and clinical approaches.
AB  - OBJECTIVE: This study compared the ways in which psychiatrists and
      nonpsychiatrists interpret the relationship between religion/spirituality and
      health and address religion/spirituality issues in the clinical encounter.
      METHOD: The authors mailed a survey to a stratified random sample of 2,000
      practicing U.S. physicians, with an oversampling of psychiatrists. The authors
      asked the physicians about their beliefs and observations regarding the
      relationship between religion/spirituality and patient health and about the ways
      in which they address religion/spirituality in the clinical setting. RESULTS: A
      total of 1,144 physicians completed the survey. Psychiatrists generally endorse
      positive influences of religion/spirituality on health, but they are more likely
      than other physicians to note that religion/spirituality sometimes causes
      negative emotions that lead to increased patient suffering (82% versus 44%).
      Compared to other physicians, psychiatrists are more likely to encounter
      religion/spirituality issues in clinical settings (92% versus 74% report their
      patients sometimes or often mention religion/spirituality issues), and they are
      more open to addressing religion/spirituality issues with patients (93% versus
      53% say that it is usually or always appropriate to inquire about
      religion/spirituality). CONCLUSIONS: This study suggests that the vast majority
      of psychiatrists appreciate the importance of religion and/or spirituality at
      least at a functional level. Compared to other physicians, psychiatrists also
      appear to be more comfortable, and have more experience, addressing
      religion/spirituality concerns in the clinical setting.

PMID- 18056238
TI  - Failure of frontolimbic inhibitory function in the context of negative emotion in
      borderline personality disorder.
AB  - OBJECTIVE: The authors sought to test the hypothesis that in patients with
      borderline personality disorder, the ventromedial prefrontal cortex and
      associated regions would not be activated during a task requiring motor
      inhibition in the setting of negative emotion. Such a finding would provide a
      plausible neural basis for the difficulty borderline patients have in modulating
      their behavior during negative emotional states and a potential marker for
      treatment interventions. METHOD: A specifically designed functional magnetic
      resonance imaging (fMRI) activation probe was used, with statistical parametric
      mapping analyses, to test hypotheses concerning decreased prefrontal inhibitory
      function in the context of negative emotion in patients with borderline
      personality disorder (N=16) and healthy comparison subjects (N=14). 3-T fMRI
      scanning was used to study brain activity while participants performed an
      emotional linguistic go/no-go task. RESULTS: Analyses confirmed that under
      conditions associated with the interaction of behavioral inhibition and negative
      emotion, borderline patients showed relatively decreased ventromedial prefrontal
      activity (including medial orbitofrontal and subgenual anterior cingulate)
      compared with healthy subjects. In borderline patients, under conditions of
      behavioral inhibition in the context of negative emotion, decreasing ventromedial
      prefrontal and increasing extended amygdalar-ventral striatal activity correlated
      highly with measures of decreased constraint and increased negative emotion,
      respectively. CONCLUSIONS: These findings suggest specific frontolimbic neural
      substrates associated with core clinical features of emotional and behavioral
      dyscontrol in borderline personality disorder.

PMID- 18056239
TI  - Altered reward processing in women recovered from anorexia nervosa.
AB  - OBJECTIVE: Individuals with anorexia nervosa are known to be ascetic and able to
      sustain self-denial of food as well as most comforts and pleasures in life.
      Building on previous findings of altered striatal dopamine binding in anorexia
      nervosa, the authors sought to assess the response of the anterior ventral
      striatum to reward and loss in this disorder. METHOD: Striatal responses to a
      simple monetary reward task were investigated using event-related functional
      magnetic resonance imaging. To avoid the confounding effects of malnutrition, the
      authors compared 13 healthy comparison women and 13 women who had recovered from
      restricting-type anorexia nervosa and had 1 year of normal weight and regular
      menstrual cycles, without binge eating or purging. RESULTS: Recovered women
      showed greater hemodynamic activation in the caudate than comparison women. Only
      the recovered women showed a significant positive relationship between trait
      anxiety and the percentage change in hemodynamic signal in the caudate during
      either wins or losses. In contrast, in the anterior ventral striatum, comparison
      women distinguished positive and negative feedback, whereas recovered women had
      similar responses to both conditions. CONCLUSIONS: Individuals who have recovered
      from anorexia nervosa may have difficulties in differentiating positive and
      negative feedback. The exaggerated activation of the caudate, a region involved
      in linking action to outcome, may constitute an attempt at "strategic" (as
      opposed to hedonic) means of responding to reward stimuli. The authors
      hypothesize that individuals with anorexia nervosa have an imbalance in
      information processing, with impaired ability to identify the emotional
      significance of a stimulus but increased traffic in neurocircuits concerned with
      planning and consequences.

PMID- 18056240
TI  - Gray matter decrease of the anterior cingulate cortex in anorexia nervosa.
AB  - OBJECTIVE: The brain regions that are critically involved in the pathophysiology
      of anorexia nervosa have not been clearly elucidated. Moreover, decrease in
      cerebral tissue during extreme malnutrition has been demonstrated repeatedly in
      anorexia nervosa, but data regarding the reversibility of this cerebral tissue
      decrease are conflicting. The authors examined region-specific gray matter
      changes and global cerebral volumes in recovered patients with anorexia nervosa.
      METHOD: High-resolution, T1-weighted magnetic resonance imaging (MRI) and voxel
      based morphometry were performed in 22 recovered women with anorexia nervosa and
      in 37 healthy comparison women. Recovery was defined as a body mass index above
      17.0 kg/m(2) and regular menses for at least 6 months. RESULTS: The global
      volumes of gray matter (but not white matter) were decreased in patients with
      anorexia nervosa by approximately 1%. Analyses of region-specific gray matter
      changes revealed a gray matter decrease bilaterally in the anterior cingulate
      cortex of approximately 5%, which remained significant after correction for
      global effects. This gray matter decrease correlated significantly with the
      lowest body mass index of lifetime but not with other clinical variables.
      CONCLUSIONS: In anorexia nervosa, part of the global gray matter loss persists
      over the long run. Region-specific gray matter loss in the anterior cingulate
      cortex is directly related to the severity of anorexia nervosa, indicating an
      important role of this area in the pathophysiology of the disorder. Further
      research is warranted to determine the cause, specificity, and functional
      consequences of this structural brain change in anorexia nervosa.

PMID- 18056241
TI  - 5-HTT binding in recovered depressed patients and healthy volunteers: a positron
      emission tomography study with [11C]DASB.
AB  - OBJECTIVE: The serotonin transporter (5-HTT) is a key target for selective
      serotonin reuptake inhibitors and may be involved in the pathophysiology of major
      depression. It is now possible to image 5-HTT directly in the human brain, but
      results from studies of acutely depressed patients have been inconsistent. The
      purpose of this study was to determine whether abnormalities in 5-HTT might be
      present in recovered depressed patients. METHOD: The authors measured the binding
      potential of 5-HTT using [11C]DASB in conjunction with positron emission
      tomography (PET) in 24 medication-free, recovered depressed male patients and 20
      healthy male comparison subjects. The regional estimates of binding potential
      were obtained using a metabolite-corrected plasma input function method followed
      by Logan analysis, with the cerebellum as a reference region. RESULTS: The
      authors found no significant difference in the binding potential of [11C]DASB
      between the recovered depressed patients and healthy comparison subjects in any
      of the brain regions (amygdala, anterior cingulate cortex, caudate nucleus,
      frontal cortex, hippocampus, insula, thalamus, and dorsal raphe) studied.
      CONCLUSIONS: Men who recover from depression have normal availability of 5-HTT in
      brain regions thought to be involved in the pathophysiology of depression. The
      findings therefore do not support the proposal that recurrent depression is
      associated with long-standing deficits in 5-HTT.

PMID- 18056242
TI  - The relationship between depressive personality disorder and major depressive
      disorder: a population-based twin study.
AB  - OBJECTIVE: One of the most important controversies regarding depressive
      personality disorder is the overlap with mood disorders. The aim of this study
      was to estimate the genetic and environmental sources of covariance between
      depressive personality disorder and major depressive disorder and to what extent
      genetic, shared, and unique environmental factors are specific to each disorder.
      METHOD: A total of 2,801 young adult twins from the Norwegian Institute of Public
      Health Twin Panel were assessed at personal interview for depressive personality
      disorder and major depressive disorder with the Structured Interview for DSM-IV
      Personality and the Composite International Diagnostic Interview. Bivariate
      Cholesky models were fitted to the data by using the Mx statistical program.
      RESULTS: In the best-fitting model, the covariation between depressive
      personality disorder and major depressive disorder were accounted for by genetic
      and unique environmental factors only. A model that did not include genetic
      factors specific to major depressive disorder was rejected. The authors found no
      clear evidence for gender differences in sources of comorbidity of depressive
      personality disorder and major depressive disorder. CONCLUSIONS: Although
      depressive personality disorder and major depressive disorder share a substantial
      proportion of genetic and environmental risk factors, the results from this study
      support the hypothesis that the two disorders are distinct entities with
      overlapping, but not identical, etiologies.

PMID- 18056243
TI  - Pupillary reactivity to emotional information in child and adolescent depression:
      links to clinical and ecological measures.
AB  - OBJECTIVE: Pupil dilation provides a quantitative index of the temporal pattern
      of brain reactivity to emotional stimuli. Previous reports indicate that
      depressed adults show sustained pupil dilation to emotional words, but this
      phenomenon has not been investigated in children. This study investigated pupil
      dilation in children with depression and examined how differences in pupillary
      responses to emotional stimuli correlate with self-rated emotional experiences in
      participants' natural environments in everyday life. METHOD: Participants were 20
      children with major depressive disorder and 22 comparison children ages 8-17.
      Pupil dilation was measured during a valence identification task. Participants
      also rated positive and negative affect in their natural environments as part of
      an ecological momentary assessment protocol. RESULTS: Children showed greater
      pupil dilation to negative words than to neutral or positive words. Children with
      major depression had diminished late pupil dilation relative to comparison
      children 9-12 sec after a negative word was presented. Diminished late pupil
      dilation to negative words was associated with greater severity of depression and
      with higher levels of negative affect and lower levels of positive affect in the
      natural environment. CONCLUSIONS: Depressed children exhibit a dynamic change in
      cognitive-affective resources devoted to processing negative emotional words,
      with more dramatic decreases than in comparison children after a negative word is
      initially processed, a pattern that differs markedly from that observed in
      depressed adults. Diminished late pupil dilation in children with major
      depression could be a marker for problems in emotional reactivity and/or
      regulation associated with pediatric depression.

PMID- 18056244
TI  - Lateralized caudate metabolic abnormalities in adolescent major depressive
      disorder: a proton MR spectroscopy study.
AB  - OBJECTIVE: Proton magnetic resonance spectroscopy ((1)H-MRS) has been
      increasingly used to examine striatal neurochemistry in adult major depressive
      disorder. This study extends the use of this modality to pediatric major
      depression to test the hypothesis that adolescents with major depression have
      elevated concentrations of striatal choline and creatine and lower concentrations
      of N-acetylaspartate. METHOD: Fourteen adolescents (ages 12-19 years, eight
      female) who had major depressive disorder for at least 8 weeks and a severity
      score of 40 or higher on the Children's Depression Rating Scale-Revised and 10
      healthy comparison adolescents (six female) group-matched for gender, age, and
      handedness were enrolled. All underwent three-dimensional 3-T (1)H-MRS at high
      spatial resolution (0.75-cm(3) voxels). Relative levels of choline, creatine, and
      N-acetylaspartate in the left and right caudate, putamen, and thalamus were
      scaled into concentrations using phantom replacement, and levels were compared
      for the two cohorts. RESULTS: Relative to comparison subjects, adolescents with
      major depressive disorder had significantly elevated concentrations of choline
      (2.11 mM versus 1.56 mM) and creatine (6.65 mM versus 5.26 mM) in the left
      caudate. No other neurochemical differences were observed between the groups.
      CONCLUSIONS: These findings most likely reflect accelerated membrane turnover and
      impaired metabolism in the left caudate. The results are consistent with prior
      imaging reports of focal and lateralized abnormalities in the caudate in adult
      major depression.

PMID- 18056245
TI  - Association between brain-derived neurotrophic factor Val66Met gene polymorphism
      and progressive brain volume changes in schizophrenia.
AB  - OBJECTIVE: Factors underlying progressive brain volume changes in schizophrenia
      remain poorly understood. The authors investigated whether a gene polymorphism
      influencing neuroplasticity may contribute to longitudinal brain volume
      alterations. METHOD: High-resolution magnetic resonance (MR) images of the whole
      brain were obtained for 119 patients with recent-onset schizophrenia spectrum
      disorders. Changes in brain volumes over an average of 3 years were compared
      between brain-derived neurotrophic factor (BDNF) val66met genotype groupings.
      Exploratory analyses were conducted to examine relationships between
      antipsychotic treatment and brain volume changes as well as the effects of BDNF
      genotype on changes in cognition and symptoms. RESULTS: Significant genotype
      effects were observed on within-subject changes in volumes of frontal lobe gray
      matter, lateral ventricles, and sulcal CSF. Met allele carriers had significantly
      greater reductions in frontal gray matter volume, with reciprocal volume
      increases in the lateral ventricles and sulcal (especially frontal and temporal)
      CSF than Val homozygous patients. Independent of BDNF genotype, more
      antipsychotic exposure between MRI scans correlated with greater volume
      reductions in frontal gray matter, particularly among patients who were initially
      treatment naive. There were no statistically significant genotype effects on
      within-subject changes in cognition or symptoms. CONCLUSIONS: BDNF(Met) variant
      may be one of several factors affecting progressive brain volume changes in
      schizophrenia.

PMID- 18056246
TI  - Physiology of schizophrenia, bipolar disorder, and schizoaffective disorder.
AB  - OBJECTIVE: Endophenotypes have been proposed to identify the genetic and
      biological substrates of complex disorders. Three physiological inhibitory
      endophenotypes of large effect size in schizophrenia include suppression of P50
      auditory evoked responses, inhibition of leading (small anticipatory) saccades
      during smooth pursuit eye movements, and cancellation of reflexive saccades in
      the antisaccade eye movement task. The aim of this study was to determine if the
      pattern of endophenotype abnormalities within individuals with schizophrenia
      differed from that within individuals with bipolar disorder. A second aim was to
      determine whether subjects with schizoaffective disorder, bipolar type, were
      neurophysiologically more similar to subjects with schizophrenia or subjects with
      bipolar disorder. METHOD: Endophenotypes were recorded for subjects diagnosed
      with schizophrenia (N=29), bipolar disorder (DSM-IV-TR) (N=40), and
      schizoaffective disorder, bipolar type (N=18). Data from normal comparison
      subjects were used to establish normal performance. RESULTS: Logistic regression
      determined that P50 ratio and frequency of leading saccades identified subjects
      with schizophrenia and bipolar disorder with a sensitivity of 95% and a
      specificity of 83%. The schizoaffective disorder group was split, with six
      subjects physiologically classified as schizophrenia-like and 12 subjects as
      bipolar-like. Those classified as schizophrenia-like were significantly younger
      at illness onset and had higher symptom ratings. CONCLUSION: A composite
      endophenotype of P50 ratio and frequency of leading saccades is consistent with
      the current clinical nosology of schizophrenia and bipolar disorder and parses
      patients with schizoaffective disorder, bipolar type, into two subgroups.

PMID- 18056247
TI  - SSRI prescriptions and the rate of suicide.

PMID- 18056248
TI  - The black box warning: decreased prescriptions and increased youth suicide?

PMID- 18056249
TI  - Withdrawal of attention rather than pharmacological treatment affects suicide
      rates in depressed children and adolescents.

PMID- 18056250
TI  - Challenge to atypical antipsychotic drug effect on cognition.

PMID- 18056251
TI  - Hyperammonemia and valproic acid-induced encephalopathy.

PMID- 18056252
TI  - Treatment of Tourette's syndrome with finasteride.

PMID- 18056254
TI  - CYP2D6-Mediated metabolism of a novel acyl coenzyme A:cholesterol acyltransferase
      inhibitor, pactimibe, and its unique plasma metabolite, R-125528.
AB  - Pactimibe sulfate is a novel acyl coenzyme A:cholesterol acyltransferase
      inhibitor. We conducted metabolic studies of pactimibe and its plasma metabolite,
      R-125528. Pactimibe had multiple metabolic pathways including indolin oxidation
      to form R-125528, omega-1 oxidation, N-dealkylation, and glucuronidation. Among
      them, the indolin oxidation and the omega-1 oxidation were dominant and were
      mainly catalyzed by CYP3A4 and CYP2D6, respectively. The intrinsic clearance
      (CL(int)) values for these pathways in human hepatic microsomes were 0.63 and
      0.76 microl/min/mg-protein, respectively. On the other hand, the metabolic
      reaction for R-125528 was restricted. It was demonstrated that omega-1 oxidation
      was the only pathway that could eliminate R-125528 from the systemic circulation.
      To our surprise, only CYP2D6-expressing microsomes could catalyze the reaction,
      and omega-1 oxidation was strongly correlated with the CYP2D6 marker reaction,
      dextromethorphan O-demethylation (r(2) = 0.90), in human hepatic microsomes.
      Although R-125528 is an atypical substrate for CYP2D6 because of its acidity, the
      K(m) value was 1.8 microM for the reaction in human hepatic microsomes and the
      CL(int) value was as high as 75.0 microl/min/mg-protein. These results suggested
      that the systemic clearance of R-125528 was highly dependent on CYP2D6 activity
      and that several studies with CYP2D6 including drug-drug interaction and
      polymorphism sensitivity should be performed during development from the
      viewpoint of metabolite safety assessment. The finding that R-125528, an acidic
      compound devoid of basic nitrogen, was a good substrate for CYP2D6 raised a
      question about previously reported CYP2D6 models based on a critical
      electrostatic interaction with Asp(301) and/or Glu(216).

PMID- 18056255
TI  - Characterization and comparative studies of zebrafish and human recombinant
      dihydrofolate reductases--inhibition by folic acid and polyphenols.
AB  - Dihydrofolate reductase (DHFR) catalyzes folic acid reduction and recycles
      dihydrofolate generated during dTMP biosynthesis to tetrahydrofolate. DHFR is the
      main target of methotrexate, the most widely used agent for antifolate therapy.
      Nevertheless, the emergence of methotrexate-resistance has greatly impeded the
      curative potential of this drug. Therefore, drugs with improved efficacy are
      still in demand, as well as an efficient in vitro assay system and animal model
      for antifolate drug discovery. The aim of this study is to evaluate the
      suitability of using zebrafish DHFR as an alternative assay system for antifolate
      drug discovery. The cDNAs encoding zebrafish and human DHFR were cloned,
      overexpressed, and purified. Similar structural and kinetic properties were
      revealed between zebrafish and human recombinant DHFRs. The susceptibilities of
      both enzymes to known DHFR inhibitors, including methotrexate and trimethoprim,
      and compounds with antifolate potential, such as polyphenols, are also
      comparable. In addition, the DHFR-mediated dihydrofolate reduction was
      significantly inhibited by its own substrate folic acid. An unexpected tissue
      specific distribution of DHFR was observed with the highest level present in ova
      and brains of zebrafish. DHFR is also abundant in zebrafish embryos of early
      stages and decreased abruptly after 3 days postfertilization. The substantial
      resemblance between zebrafish and human DHFRs, as demonstrated in this study,
      provides compelling evidence supporting the use of zebrafish DHFR as an in vitro
      assay system for folate-related studies and drug discovery.

PMID- 18056257
TI  - An endothelial cell genetic screen identifies the GTPase Rem2 as a suppressor of
      p19ARF expression that promotes endothelial cell proliferation and angiogenesis.
AB  - Angiogenesis requires an increase in endothelial cell proliferation to support an
      increase in mass of blood vessels. We designed an in vitro endothelial cell model
      to functionally screen for genes that regulate endothelial cell proliferation. A
      gain of function screen for genes that bypass p53 endothelial cell arrest
      identified Rem2, a Ras-like GTPase. We show that ectopic Rem2 suppresses p14(ARF)
      (human) or p19(ARF) (mouse) expression that leads to increased endothelial cell
      proliferation. Conversely, loss of ectopic Rem2 by RNA interference restores
      p19(ARF) expression in endothelial cells. We further show that Rem2-interacting
      14-3-3 proteins are involved in the cell localization of Rem2, regulation of
      p19(ARF) expression, and endothelial cell proliferation. Finally, we demonstrate
      using the RIP1 tag2 mouse model of pancreatic disease that Rem2 is up-regulated
      in endothelial cells of stage IV disease. The data unravel a possible molecular
      mechanism for Rem2-induced angiogenesis and suggests Rem2 as a potential novel
      target for treating pathological angiogenesis.

PMID- 18056256
TI  - Quantitative analysis of synaptic phosphorylation and protein expression.
AB  - The postsynaptic density (PSD) signaling machinery contains proteins with diverse
      functions. Brain region-specific variations in PSD components mediate distinct
      physiological responses to synaptic activation. We have developed mass
      spectrometry-based methods to comprehensively compare both relative protein
      expression and phosphorylation status from proteins present in biochemical
      preparations of postsynaptic density. Using these methods, we determined the
      relative expression of 2159 proteins and 1564 phosphorylation sites in PSD
      preparations from murine cortex, midbrain, cerebellum, and hippocampus. These
      experiments were conducted twice using independent biological replicates, which
      allowed us to assess the experimental and biological variability in this system.
      Concerning protein expression, cluster analysis revealed that known functionally
      associated proteins display coordinated synaptic expression. Therefore, proteins
      identified as co-clustering with known protein complexes are prime candidates for
      assignment as previously unrecognized components. Concerning degree of
      phosphorylation, we observed more extensive phosphorylation sites on N-methyl-D
      aspartate (NMDA) receptors than alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptors, consistent with the central role of N
      methyl-D-aspartate receptors in processing synaptic transmission patterns.
      Average kinase and phosphatase levels were highest in the hippocampus,
      correlating with a higher overall phosphopeptide abundance present in this brain
      region. These findings suggest that the hippocampus utilizes reversible protein
      phosphorylation to a greater extent than other brain regions when modifying
      synaptic strength.

PMID- 18056258
TI  - Platelet fragmentation requires a specific structural conformation of human
      monoclonal antibody against beta3 integrin.
AB  - We have described an autoantibody against beta3 (GPIIIa49-66), a region of
      platelet integrin alphaIIbbeta3 that is unique. It induces platelet fragmentation
      in the absence of complement via antibody activation of platelet NADPH oxidase
      and 12-lipoxygenase to release reactive oxygen species, which destroy platelets.
      To study the mechanism of anti-GPIIIa antibody-induced platelet fragmentation, we
      screened a human single chain Fv antibody library with the GPIIIa49-66 peptide.
      Nine monoclonal antibodies were identified that were capable of binding to
      GPIIIa49-66. Surprisingly, binding avidity for GPIIIa49-66 did not correlate with
      activity of induction of platelet fragmentation. We therefore investigated the
      requirements for platelet fragmentation. Mutations were introduced into the heavy
      chain complementary-determining region-3 of clones 11, 43, and 54 by site
      directed mutagenesis. The capability of these clones to induce platelet
      fragmentation or bind to GPIIIa49-66 subsequently changed. Molecular modeling of
      these clones with their mutants revealed that the ability to induce platelet
      fragmentation is affected by the side chain orientation of positively charged
      amino acids in the heavy chain of residues 99-102. Thus, a structural change in
      the conformation of anti-GPIIIa49-66 antibody contributes to its binding to the
      beta3 integrin and subsequent antibody-induced platelet fragmentation and
      aggregate dissolution.

PMID- 18056259
TI  - MAP1A light chain-2 interacts with GTP-RhoB to control epidermal growth factor
      (EGF)-dependent EGF receptor signaling.
AB  - Rho GTPases have been implicated in the control of several cellular functions,
      including regulation of the actin cytoskeleton, cell proliferation, and
      oncogenesis. Unlike RhoA and RhoC, RhoB localizes in part to endosomes and
      controls endocytic trafficking. Using a yeast two-hybrid screen and a glutathione
      S-transferase pulldown assay, we identified LC2, the light chain of the
      microtubule-associated protein MAP1A, as a novel binding partner for RhoB. GTP
      binding and the 18-amino acid C-terminal hypervariable domain of RhoB are
      critical for its binding to MAP1A/LC2. Coimmunoprecipitation and
      immunofluorescence experiments showed that this interaction occurs in U87 cells.
      Down-regulation of MAP1A/LC2 expression decreased epidermal growth factor (EGF)
      receptor expression and modified the signaling response to EGF treatment. We
      concluded that MAP1A/LC2 is critical for RhoB function in EGF-induced EGF
      receptor regulation. Because MAP1A/LC2 is thought to function as an adaptor
      between microtubules and other molecules, we postulate that the RhoB and
      MAP1A/LC2 interactions facilitate endocytic vesicle trafficking and regulate the
      trafficking of signaling molecules.

PMID- 18056260
TI  - Smarcd3 regulates the timing of zebrafish myogenesis onset.
AB  - A cascade of signaling events triggers myogenesis in vertebrates. Although
      studies of zebrafish indicate that fibroblast growth factor (Fgf), Hedgehog (Hh),
      and the T-box transcription factors, No tail (Ntl) and T-box gene 16 (Tbx16),
      regulate myogenesis, the hierarchy of these factors has not been determined.
      Recently, another transcriptional cofactor, Smarcd3, a subunit of the SWI/SNF
      chromatin-remodeling complex, has been shown to be required for heart muscle
      formation in mouse. In zebrafish, fgf8 and ntl expression commences during
      blastula stages, whereas myogenesis, as indicated by myod expression, does not
      begin until much later during mid-gastrula stages. smarcd3b expression, on the
      other hand, becomes enriched in the marginal zone just prior to the beginning of
      myod expression. Overexpression of smarcd3 shifts the onset of myod and myf5
      expression earlier, and myod and myf5 expression in adaxial cells, the earliest
      muscle precursors, requires Smarcd3, indicating that Smarcd3 is the limiting
      factor that regulates the onset of myogenesis. Smarcd3 physically interacts with
      Ntl, and Smarcd3 overexpression fails to rescue myod expression in ntl mutants,
      demonstrating that function of Smarcd3 depends on Ntl activity. We propose a
      model in which cooperative activity of Fgf, Ntl, and Smarcd3 is required for the
      onset of myogenesis, with Smarcd3b serving as the primary regulator of the timing
      of myogenesis onset.

PMID- 18056261
TI  - Human kallikrein-related peptidase 14 (KLK14) is a new activator component of the
      KLK proteolytic cascade. Possible function in seminal plasma and skin.
AB  - Human kallikrein-related peptidases (KLKs) are a family of 15 serine proteases
      mainly known for their biomarker utility in various neoplastic and non-neoplastic
      diseases. Despite significant progress in understanding their clinical
      application, little is known about the activation mechanism(s) of this important
      family of enzymes. Emerging evidence indicates that KLKs are activated in a
      stepwise manner, which is a characteristic of proteolytic cascades. Thus far, KLK
      cascades have been implicated in semen liquefaction and skin desquamation. Many
      members of the KLK family have been reported to be active in seminal plasma
      and/or skin, suggesting their involvement in common proteolytic cascades. KLK14,
      in particular, is highly active and has recently been proposed as one of the key
      trypsin-like proteases involved in skin desquamation. This study aims to
      elucidate a probable cascade-mediated role of KLK14 by 1) examining KLK14
      mediated cleavage of a heptapeptide library encompassing activation sites of the
      15 KLKs and 2) verifying activation of certain candidate downstream targets of
      KLK14 (i.e. pro-KLK1, -KLK3, and -KLK11). Heptapeptides encompassing activation
      motifs of KLK2, -3, -5, and -11 were cleaved with a high (> or =85%) cleavage
      efficiency. Activation of these candidates was confirmed using full-length
      recombinant proteins. Pro-KLK11, -KLK3, and -KLK1 were rapidly activated in a
      concentration-dependent manner. Pro-KLK3 regulation was bidirectional because
      activation was followed by inactivation via internal cleavage of active KLK3. We
      are proposing a putative cascade model, operating through multiple KLKs.
      Identification of novel members of such proteolytic cascades will aid in further
      defining mechanisms involved in seminal/skin homeostasis.

PMID- 18056262
TI  - Scythe regulates apoptosis-inducing factor stability during endoplasmic reticulum
      stress-induced apoptosis.
AB  - Scythe (BAT3; HLA-B associated transcript 3, Bag 6) is a protein that has been
      implicated in apoptosis because it can modulate the Drosophila melanogaster
      apoptotic regulator, Reaper. Mice lacking Scythe show pronounced defects in
      organogenesis and in the regulation of apoptosis and proliferation during
      mammalian development. However, the biochemical pathways important for Scythe
      function are unknown. We report here multiple levels of interaction between
      Scythe and the apoptogenic mitochondrial intermembrane protein AIF (apoptosis
      inducing factor). Scythe physically interacts with AIF and regulates its
      stability. AIF stability is markedly reduced in Scythe(-/-) cells, which are more
      resistant to endoplasmic reticulum stress induced by thapsigargin. Reintroduction
      of Scythe or overexpression of AIF in Scythe(-/-) cells restores their
      sensitivity to apoptosis. Together, these data implicate Scythe as a regulator of
      AIF.

PMID- 18056263
TI  - Norepinephrine- and epinephrine-induced distinct beta2-adrenoceptor signaling is
      dictated by GRK2 phosphorylation in cardiomyocytes.
AB  - Agonist-dependent activation of G protein-coupled receptors induces diversified
      receptor cellular and signaling properties. Norepinephrine (NE) and epinephrine
      (Epi) are two endogenous ligands that activate adrenoceptor (AR) signals in a
      variety of physiological stress responses in animals. Here we use cardiomyocyte
      contraction rate response to analyze the endogenous beta(2)AR signaling induced
      by Epi or NE in cardiac tissue. The Epi-activated beta(2)AR induced a rapid
      contraction rate increase that peaked at 4 min after stimulation. In contrast,
      the NE-activated beta(2)AR induced a much slower contraction rate increase that
      peaked at 10 min after stimulation. Whereas both drugs activated beta(2)AR
      coupling to G(s) proteins, only Epi-activated receptors were capable of coupling
      to G(i) proteins. Subsequent studies showed that the Epi-activated beta(2)AR
      underwent a rapid phosphorylation by G protein-coupled receptor kinase 2 (GRK2)
      and subsequent dephosphorylation on serine residues 355 and 356, which was
      critical for sufficient receptor recycling and G(i) coupling. In contrast, the NE
      activated beta(2)ARs underwent slow GRK2 phosphorylation, receptor
      internalization and recycling, and failed to couple to G(i). Moreover, inhibiting
      beta(2)AR phosphorylation by betaARK C terminus or dephosphorylation by okadaic
      acid prevented sufficient recycling and G(i) coupling. Together, our data
      revealed that distinct temporal phosphorylation of beta(2)AR on serine 355 and
      356 by GRK2 plays a critical role for dictating receptor cellular events and
      signaling properties induced by Epi or NE in cardiomyocytes. This study not only
      helps us understand the endogenous agonist-dependent beta(2)AR signaling in
      animal heart but also offers an example of how G protein-coupled receptor
      signaling may be finely regulated by GRK in physiological settings.

PMID- 18056264
TI  - Specific recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 guanine nucleotide
      exchange factors.
AB  - Recognition of cognate Rho GTPases by guanine-nucleotide exchange factors (GEF)
      is fundamental to Rho GTPase signaling specificity. Two main GEF families use
      either the Dbl homology (DH) or the DOCK homology region 2 (DHR-2) catalytic
      domain. How DHR-2-containing GEFs distinguish between the GTPases Rac and Cdc42
      is not known. To determine how these GEFs specifically recognize the two Rho
      GTPases, we studied the amino acid sequences in Rac2 and Cdc42 that are crucial
      for activation by DOCK2, a Rac-specific GEF, and DOCK9, a distantly related Cdc42
      specific GEF. Two elements in the N-terminal regions of Rac2 and Cdc42 were found
      to be essential for specific interactions with DOCK2 and DOCK9. One element
      consists of divergent amino acid residues in the switch 1 regions of the GTPases.
      Significantly, these residues were also found to be important for GTPase
      recognition by Rac-specific DOCK180, DOCK3, and DOCK4 GEFs. These findings were
      unexpected because the same residues were shown previously to interact with
      GTPase effectors rather than GEFs. The other element comprises divergent residues
      in the beta3 strand that are known to mediate specific recognition by DH domain
      containing GEFs. Remarkably, Rac2-to-Cdc42 substitutions of four of these
      residues were sufficient for Rac2 to be specifically activated by DOCK9. Thus,
      DOCK2 and DOCK9 specifically recognize Rac2 and Cdc42 through their switch 1 as
      well as beta2-beta3 regions and the mode of recognition via switch 1 appears to
      be conserved among diverse Rac-specific DHR-2 GEFs.

PMID- 18056265
TI  - Activin A/bone morphogenetic protein (BMP) chimeras exhibit BMP-like activity and
      antagonize activin and myostatin.
AB  - Activins and bone morphogenetic proteins (BMPs) are members of the transforming
      growth factor-beta family of growth and differentiation factors that induce
      signaling in target cells by assembling type II and type I receptors at the cell
      surface. Ligand residues involved in type II binding are located predominantly in
      the C-terminal region that forms an extended beta-sheet, whereas residues
      involved in type I binding are located in the alpha-helical and preceding loop
      central portion of the molecule. To test whether the central residues are
      sufficient to determine specificity toward type I receptors, activin A/BMP
      chimeras were constructed in which the central residues (45-79) of activin A were
      replaced with corresponding residues of BMP2 and BMP7. The chimeras were assessed
      for activin type II receptor (Act RII) binding, activin-like bioactivity, and BMP
      like activity as well as antagonistic properties toward activin A and myostatin.
      ActA/BMP7 chimera retained Act RII binding affinity comparable with wild type
      activin A, whereas ActA/BMP2 chimera showed a slightly reduced affinity toward
      Act RII. Both the chimeras were devoid of significant activin bioactivity in 293T
      cells in the A3 Lux reporter assay up to concentrations 10-fold higher than the
      minimal effective activin A concentration (approximately 4 nM). In contrast,
      these chimeras showed BMP-like activity in a BRE-Luc assay in HepG2 cells as well
      as induced osteoblast-like phenotype in C2C12 cells expressing alkaline
      phosphatase. Furthermore, both the chimeras activated Smad1 but not Smad2 in
      C2C12 cells. Also, both the chimeras antagonized ligands that signal via activin
      type II receptor, such as activin A and myostatin. These data indicate that
      activin residues in the central region determine its specificity toward type I
      receptors. ActA/BMP chimeras can be useful in the study of receptor specificities
      and modulation of transforming growth factor-beta members, activins, and BMPs.

PMID- 18056266
TI  - Heparin strongly enhances the formation of beta2-microglobulin amyloid fibrils in
      the presence of type I collagen.
AB  - The tissue specificity of fibrillar deposition in dialysis-related amyloidosis is
      most likely associated with the peculiar interaction of beta2-microglobulin
      (beta2-m) with collagen fibers. However, other co-factors such as
      glycosaminoglycans might facilitate amyloid formation. In this study we have
      investigated the role of heparin in the process of collagen-driven
      amyloidogenesis. In fact, heparin is a well known positive effector of
      fibrillogenesis, and the elucidation of its potential effect in this type of
      amyloidosis is particularly relevant because heparin is regularly given to
      patients subject to hemodialysis to prevent blood clotting. We have monitored by
      atomic force microscopy the formation of beta2-m amyloid fibrils in the presence
      of collagen fibers, and we have discovered that heparin strongly accelerates
      amyloid deposition. The mechanism of this effect is still largely unexplained.
      Using dynamic light scattering, we have found that heparin promotes beta2-m
      aggregation in solution at pH 6.4. Morphology and structure of fibrils obtained
      in the presence of collagen and heparin are highly similar to those of natural
      fibrils. The fibril surface topology, investigated by limited proteolysis,
      suggests that the general assembly of amyloid fibrils grown under these
      conditions and in vitro at low pH is similar. The exposure of these fibrils to
      trypsin generates a cleavage at the C-terminal of lysine 6 and creates the 7-99
      truncated form of beta2-m (DeltaN6beta2-m) that is a ubiquitous constituent of
      the natural beta2-m fibrils. The formation of this beta2-m species, which has a
      strong propensity to aggregate, might play an important role in the acceleration
      of local amyloid deposition.

PMID- 18056267
TI  - Conformational changes in a pore-lining helix coupled to cystic fibrosis
      transmembrane conductance regulator channel gating.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR), the protein
      dysfunctional in cystic fibrosis, is unique among ATP-binding cassette
      transporters in that it functions as an ion channel. In CFTR, ATP binding opens
      the channel, and its subsequent hydrolysis causes channel closure. We studied the
      conformational changes in the pore-lining sixth transmembrane segment upon ATP
      binding by measuring state-dependent changes in accessibility of substituted
      cysteines to methanethiosulfonate reagents. Modification rates of three residues
      (resides 331, 333, and 335) near the extracellular side were 10-1000-fold slower
      in the open state than in the closed state. Introduction of a charged residue by
      chemical modification at two of these positions (resides 331 and 333) affected
      CFTR single-channel gating. In contrast, modifications of pore-lining residues
      334 and 338 were not state-dependent. Our results suggest that ATP binding
      induces a modest conformational change in the sixth transmembrane segment, and
      this conformational change is coupled to the gating mechanism that regulates ion
      conduction. These results may establish a structural basis of gating involving
      the dynamic rearrangement of transmembrane domains necessary for vectorial
      transport of substrates in ATP-binding cassette transporters.

PMID- 18056268
TI  - Down-regulation of caveolin-1, an inhibitor of transforming growth factor-beta
      signaling, in acute allergen-induced airway remodeling.
AB  - Asthma can progress to subepithelial airway fibrosis, mediated in large part by
      transforming growth factor-beta (TGF-beta). The scaffolding protein caveolin-1
      (cav1) can inhibit the activity of TGF-beta, perhaps by forming membrane
      invaginations that enfold TGF-beta receptors. The study goals were 1) to evaluate
      how allergen challenge affects lung expression of cav1 and the density of
      caveolae in vivo 2) to determine whether reduced cav1 expression is mediated by
      interleukin (IL)-4 and 3) to measure the effects of decreased expression of cav1
      on TGF-beta signaling. C57BL/6J, IL-4-deficient mice, and cav1-deficient mice,
      sensitized by intraperitoneal injections of phosphate-buffered saline or
      ovalbumin (OVA) at days 0 and 12, received intranasal phosphate-buffered saline
      or OVA challenges at days 24, 26, and 28. Additionally, another group of C57BL/6J
      mice received IL-4 by intratracheal instillation for 7 days. We confirmed that
      the OVA-allergen challenge increased eosinophilia and T-helper type 2-related
      cytokine levels (IL-4, IL-5, and IL-13) in bronchoalveolar lavage. Allergen
      challenge reduced lung cav1 mRNA abundance by 40%, cav1 protein by 30%, and the
      number of lung fibroblast caveolae by 50%. Administration of IL-4 in vivo also
      substantially decreased cav1 expression. In contrast, the allergen challenge did
      not decrease cav1 expression in IL-4-deficient mice. The reduced expression of
      cav1 was associated with activation of TGF-beta signaling that was further
      enhanced in OVA-sensitized and challenged cav1-deficient mice. This study
      demonstrates a previously unknown modulation of TGF-beta signaling by IL-4, via
      cav1, suggesting novel therapeutic targets for controlling the effects of TGF
      beta and thereby ameliorating pathological airway remodeling.

PMID- 18056269
TI  - Telithromycin resistance in Streptococcus pneumoniae is conferred by a deletion
      in the leader sequence of erm(B) that increases rRNA methylation.
AB  - A telithromycin-resistant clinical isolate of Streptococcus pneumoniae (strain
      P1501016) has been found to contain a version of erm(B) that is altered by a 136
      bp deletion in the leader sequence. By allele replacement mutagenesis, a second
      strain of S. pneumoniae (PC13) with a wild-type erm(B) gene was transformed to
      the telithromycin-resistant phenotype by introduction of the mutant erm(B) gene.
      Whereas the wild-type PC13 strain showed slight telithromycin resistance only
      after induction by erythromycin (telithromycin MIC increased from 0.06 to 0.5
      microg/ml), the transformed PC13 strain is constitutively resistant (MIC of 16
      mug/ml). Expression of erm(B) was quantified by real-time reverse transcription
      PCR in the presence of erythromycin or telithromycin; erm(B) expression was
      significantly higher in the transformed PC13 strain than the wild-type strain.
      Furthermore, the transformed strain had significantly higher levels of ribosomal
      methylation in the absence as well as in the presence of the antibiotics. Growth
      studies showed that the transformed PC13 strain had a shorter lag phase than the
      wild-type strain in the presence of erythromycin. Telithromycin resistance is
      conclusively shown to be conferred by the mutant erm(B) gene that is expressed at
      a constitutively higher level than the inducible wild-type gene. Elevated erm(B)
      expression results in a higher level of rRNA methylation that presumably hinders
      telithromycin binding to the ribosome.

PMID- 18056270
TI  - Role of a sodium-dependent symporter homologue in the thermosensitivity of beta
      lactam antibiotic resistance and cell wall composition in Staphylococcus aureus.
AB  - Expression of high-level beta-lactam resistance is known to be thermosensitive in
      many methicillin-resistant Staphylococcus aureus (MRSA) strains, including strain
      COL, in which the high methicillin MIC for cultures grown at 37 degrees C (800
      microg/ml) was reduced to 12 microg/ml at 42 degrees C. COL grew faster at 42
      degrees C than at 37 degrees C and at the higher temperature produced cell walls
      of abnormal composition: there was an over-representation of the monomeric
      muropeptide without the oligoglycine chain and an increase in the representation
      of multimers that contained this wall component as the donor molecule. Screening
      of a Tn551 insertional library for mutants, in which the high and homogenous beta
      lactam antibiotic resistance of strain COL is retained at 42 degrees C,
      identified mutant C245, which expressed high-level methicillin resistance and
      produced a cell wall of normal composition independent of the temperature. The
      Tn551 inactivated gene was found, by homology search, to encode for a sodium
      dependent symporter, homologues of which are ubiquitous in both prokaryotic and
      eukaryotic genomes. Inactivation of this putative symporter in several
      heteroresistant clinical MRSA isolates caused striking increases in the level of
      their beta-lactam resistance.

PMID- 18056271
TI  - Pharmacokinetic interaction between fosamprenavir-ritonavir and rifabutin in
      healthy subjects.
AB  - Rifabutin (RFB) is administered for treatment of tuberculosis and Mycobacterium
      avium complex infection, including use for patients coinfected with human
      immunodeficiency virus (HIV). Increased systemic exposure to RFB and its
      equipotent active metabolite, 25-O-desacetyl-RFB (dAc-RFB), has been reported
      during concomitant administration of CYP3A4 inhibitors, including ritonavir
      (RTV), lopinavir, and amprenavir (APV); therefore, a reduction in the RFB dosage
      is recommended when it is coadministered with these protease inhibitors.
      Fosamprenavir (FPV), the phosphate ester prodrug of the HIV type 1 protease
      inhibitor APV, is administered either with or without RTV. A randomized, open
      label, two-period, two-sequence, balanced, crossover drug interaction study was
      conducted with 22 healthy adult subjects to compare steady-state plasma RFB
      pharmacokinetic parameters during concomitant administration of FPV-RTV (700/100
      mg twice a day [BID]) with a 75%-reduced RFB dose (150 mg every other day [QOD])
      to the standard RFB regimen (300 mg once per day [QD]) by geometric least-squares
      mean ratios. Relative to results with RFB (300 mg QD), coadministration of dose
      adjusted RFB with FPV-RTV resulted in an unchanged RFB area under the
      concentration-time curve for 0 to 48 h (AUC(0-48)) and a 14% decrease in the
      maximum concentration of drug in plasma (C(max)), whereas the AUC(0-48) and
      C(max) of dAc-RFB were increased by 11- and 6-fold, respectively, resulting in a
      64% increase in the total antimycobacterial AUC(0-48). Relative to historical
      controls, the plasma APV AUC from 0 h to the end of the dosing interval (AUC(0
      tau)) and C(max) were increased approximately 35%, and the concentration at the
      end of the dosing interval at steady state was unchanged following
      coadministration of RFB with FPV-RTV. The safety profile of the combination of
      RFB and FPV-RTV was consistent with previously described events with RFB or FPV
      RTV alone. Based on the results of this study, a reduction in the RFB dose by >
      or =75% (to 150 mg QOD or three times per week) is recommended when it is
      coadministered with FPV-RTV (700/100 mg BID).

PMID- 18056272
TI  - Vancomycin-resistant Staphylococcus aureus isolates associated with Inc18-like
      vanA plasmids in Michigan.
AB  - Five of the seven cases of vancomycin-resistant Staphylococcus aureus (VRSA)
      infection identified to date have occurred in southeastern Michigan. VRSA
      isolates from the four most recent cases (all from Michigan) were characterized.
      The vanA gene was localized to a single plasmid in each VRSA isolate. The pulsed
      field gel electrophoresis patterns of chromosomal DNA and the restriction profile
      of the plasmid demonstrated that the four isolates were unique and differed from
      the first three VRSA isolates. Vancomycin-resistant Enterococcus (VRE) isolates,
      all of which were Enterococcus faecalis, were recovered from case patients 4 to
      6. Each VRE isolate transferred vancomycin resistance to E. faecalis JH2-2 by
      conjugation. PCRs for vanA and the Inc18-like plasmid genes traA and repR
      confirmed the presence of an Inc18-like vanA plasmid in all VRE isolates and
      transconjugants. An Inc18-like vanA plasmid was identified in the VRSA isolate
      from case patient 7. These findings suggest a role of Inc18-like plasmids as vanA
      donors.

PMID- 18056273
TI  - Community-acquired liver abscess caused by serotype K1 Klebsiella pneumoniae with
      CTX-M-15-type extended-spectrum beta-lactamase.

PMID- 18056274
TI  - In vitro activities of voriconazole, itraconazole, and terbinafine alone or in
      combination against Pythium insidiosum isolates from Brazil.
AB  - We evaluated the in vitro activities of voriconazole, itraconazole, and
      terbinafine against 30 clinical isolates of Pythium insidiosum using a
      checkerboard macrodilution method. The combined activity of terbinafine plus
      itraconazole or plus voriconazole was synergic against 17% of the strains.
      Antagonism was not observed.

PMID- 18056275
TI  - Telithromycin and quinupristin-dalfopristin induce delayed death in Plasmodium
      falciparum.
AB  - Antibacterial agents are used in malaria therapy due to their effect on two
      prokaryote organelles, the mitochondrion and the apicoplast. We demonstrate here
      that the ribosome-blocking antibiotics telithromycin and quinupristin
      dalfopristin, but not linezolid, inhibit the growth of Plasmodium falciparum.
      Both drugs induce delayed death in the parasite, suggesting that their effect
      involves the impairment of apicoplast translation processes.

PMID- 18056276
TI  - Inhibition of ABC transporters abolishes antimony resistance in Leishmania
      Infection.
AB  - The emergence of antimony (Sb) resistance has jeopardized the treatment of
      visceral leishmaniasis in various countries. Previous studies have considered the
      part played by leishmanial parasites in antimony resistance, but the involvement
      of host factors in the clinical scenario remained to be investigated. Here we
      show that unlike infection with Sb-sensitive (Sbs) Leishmania donovani, infection
      with Sb-resistant (Sb r) L. donovani induces the upregulation of multidrug
      resistance-associated protein 1 (MRP1) and permeability glycoprotein (P-gp) in
      host cells, resulting in a nonaccumulation of intracellular Sb following
      treatment with sodium antimony gluconate (SAG) favoring parasite replication. The
      inhibition of MRP1 and P-gp with resistance-modifying agents such as lovastatin
      allows Sb accumulation and parasite killing within macrophages and offers
      protection in an animal model in which infection with Sb r L. donovani is
      otherwise lethal. The occurrence of a similar scenario in clinical cases is
      supported by the findings that unlike monocytes from SAG-sensitive kala-azar (KA)
      patients, monocytes from SAG-unresponsive KA patients overexpress P-gp and MRP1
      and fail to accumulate Sb following in vitro SAG treatment unless pretreated with
      inhibitors of ABC transporters. Thus, the expression status of MRP1 and P-gp in
      blood monocytes may be used as a diagnostic marker for Sb resistance and the
      treatment strategy can be designed accordingly. Our results also indicate that
      lovastatin, which can inhibit both P-gp and MRP1, might be beneficial for
      reverting Sb resistance in leishmaniasis as well as drug resistance in other
      clinical situations, including cancer.

PMID- 18056277
TI  - In vitro interactions between tacrolimus and azoles against Candida albicans
      determined by different methods.
AB  - Combination therapy could be of use for the treatment of fungal infections,
      especially those caused by drug-resistant fungi. However, the methods and
      approaches used for data generation and result interpretation need further
      optimizing. The fractional inhibitory concentration index (FICI) is the most
      commonly used method, but it has several drawbacks in characterizing antifungal
      drug interaction. Alternatively, some new methods can be used such as the DeltaE
      model (difference between the predicted and measured fungal growth percentages)
      and the response surface approach, which uses the concentration-effect
      relationship over the whole concentration range instead of just the MIC. In the
      present study, in vitro interactions between tacrolimus (FK506) and three azoles
      fluconazole (FLC), itraconazole (ITR), and voriconazole (VRC)-against Candida
      albicans were evaluated by the checkerboard microdilution method and time-killing
      test. The intensity of the interactions was determined by visual reading and the
      spectrophotometric method in a checkerboard assay, and the nature of the
      interactions was assessed by nonparametric models of FICI and DeltaE. Colony
      counting and colorimetric viable detection methods (2,3-bis {2-methoxy-4-nitro-5
      [(sulfenylamino) carbonyl]-2H-tetrazolium hydroxide} [XTT] reduction test) were
      used for evaluating the combination antifungal effects over time. Synergistic and
      indifferent effects were found for the combination of FK506 and azoles against
      azole-sensitive strains, while strong synergy was found against azole-resistant
      strains analyzed by FICI. The DeltaE model gave more consistent results with
      FICI. The positive interactions were also confirmed by the time-killing test. Our
      findings suggest a potential role for combination therapy with calcineurin
      pathway inhibitors and azoles to augment activity against resistant C. albicans.

PMID- 18056278
TI  - Cidofovir and (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine are highly
      effective inhibitors of vaccinia virus DNA polymerase when incorporated into the
      template strand.
AB  - The acyclic nucleoside phosphonate drug (S)-9-[3-hydroxy-(2
      phosphonomethoxy)propyl]adenine [(S)-HPMPA], is a broad-spectrum antiviral and
      antiparasitic agent. Previous work has shown that the active intracellular
      metabolite of this compound, (S)-HPMPA diphosphate [(S)-HPMPApp], is an analog of
      dATP and targets DNA polymerases. However, the mechanism by which (S)-HPMPA
      inhibits DNA polymerases remains elusive. Using vaccinia virus as a model system,
      we have previously shown that cidofovir diphosphate (CDVpp), an analog of dCTP
      and a related antiviral agent, is a poor substrate for the vaccinia virus DNA
      polymerase and acts to inhibit primer extension and block 3'-to-5' proofreading
      exonuclease activity. Based on structural similarities and the greater antiviral
      efficacy of (S)-HPMPA, we predicted that (S)-HPMPApp would have a similar, but
      more pronounced effect on vaccinia polymerase than CDVpp. Interestingly, we found
      that (S)-HPMPApp is a good substrate for the viral enzyme, exhibiting K(m) and
      V(max) parameters comparable to those of dATP, and certainly not behaving like
      CDVpp as a functional chain terminator. Metabolic experiments indicated that (S)
      HPMPA is converted to (S)-HPMPApp to a much greater extent than CDV is converted
      to CDVpp, although both drugs cause identical effects on virus DNA replication at
      their 50% effective concentration. Subsequent studies showed that both compounds
      can be faithfully incorporated into DNA, but when CDV and (S)-HPMPA are
      incorporated into the template strand, both strongly inhibit trans-lesion DNA
      synthesis. It thus appears that nucleoside phosphonate drugs exhibit at least two
      different effects on DNA polymerases depending upon in what form the enzyme
      encounters the drug.

PMID- 18056279
TI  - Posaconazole activity against Candida glabrata after exposure to caspofungin or
      amphotericin B.
AB  - We evaluated the effects of sequential therapy with caspofungin (CAS) or
      amphotericin B (AMB) followed by posaconazole (POS) against Candida glabrata. The
      susceptibilities to POS of yeast cells pre-exposed to CAS or AMB were identical
      to those of untreated cells as shown by standard Clinical and Laboratory
      Standards Institute broth dilution, cell viability, and disk diffusion methods.
      We then investigated the activity of sequential regimens in an experimental model
      of disseminated candidiasis. CAS given at 1 mg/kg/day for 2 days followed by POS
      at either 15 or 30 mg/kg/day significantly reduced the counts compared to the
      controls, but this treatment was not superior to the use of CAS alone. Also,
      sequential regimens with AMB given at 1 mg/kg/day for 2 days followed by POS
      (AMB/POS) were effective at reducing the fungal burden against the controls. In
      addition, AMB/POS with both doses of the triazole were significantly more
      effective than AMB alone. Overall, our data showed that there is no therapeutic
      advantage in using CAS followed by POS, whereas an induction therapy with AMB
      followed by a maintenance regimen with POS might be a suitable strategy in
      managing C. glabrata infections.

PMID- 18056280
TI  - Entecavir for treatment of hepatitis B virus displays no in vitro mitochondrial
      toxicity or DNA polymerase gamma inhibition.
AB  - Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be
      associated with mitochondrial toxicity. In vitro studies have been used to
      predict the predisposition for and characterize the mechanisms causing
      mitochondrial toxicity. Entecavir (ETV) is an approved deoxyguanosine nucleoside
      for the treatment of chronic hepatitis B virus (HBV) infection that exhibits
      potent activity against viral reverse transcriptase. We assessed the potential
      for mitochondrial toxicity of ETV in long-term cultures of HepG2 hepatoma cells
      by measuring mitochondrial function (through lactate secretion), levels of
      mitochondrial DNA (mtDNA), and levels of mitochondrial proteins COX II and COX
      IV. Furthermore, we tested the activity of ETV-triphosphate (ETV-TP) against
      mitochondrial DNA polymerase gamma (Pol gamma) in vitro. ETV concentrations as
      high as 100 times the maximal clinical exposure (C(max)) did not affect cell
      proliferation, levels of lactate, mitochondrial DNA, or mitochondrial proteins
      throughout the 15-day culture. The lack of mitochondrial toxicity was consistent
      with the finding that ETV-TP was not recognized by mitochondrial DNA Pol gamma
      and failed to be incorporated into DNA or inhibit the polymerase assay at the
      highest levels tested, 300 microM. Combinations of ETV with each of the other HBV
      NRTI antivirals, adefovir, tenofovir, and lamivudine at 10 times their respective
      C(max) levels also failed to result in cellular or mitochondrial toxicity. In
      summary, cell culture and enzymatic studies yielded no evidence that would
      predict mitochondrial toxicity of ETV at exposure levels in excess of those
      expected to be achieved clinically.

PMID- 18056281
TI  - Intracellular metabolism of the nucleotide prodrug GS-9131, a potent anti-human
      immunodeficiency virus agent.
AB  - GS-9131 is a phosphonoamidate prodrug of the novel ribose-modified phosphonate
      nucleotide analog GS-9148 that demonstrates potent anti-human immunodeficiency
      virus type 1 (HIV-1) activity and an excellent resistance profile in vitro.
      Prodrug moieties were optimized for the efficient delivery of GS-9148 and its
      active diphosphate (DP) metabolite to lymphoid cells following oral
      administration. To understand the intracellular pharmacology of GS-9131,
      incubations were performed with various types of lymphoid cells in vitro. The
      intracellular accumulation and antiviral activity levels of GS-9148 were limited
      by its lack of cellular permeation, and GS-9131 increased the delivery of GS-9148
      DP by 76- to 290-fold relative to that of GS-9148. GS-9131 activation was
      saturable at high extracellular concentrations, potentially due to a high
      affinity promoiety cleavage step. Once inside the cells, GS-9148 was efficiently
      phosphorylated, forming similar amounts of anabolites in primary lymphoid cells.
      The levels of GS-9148-DP formed in peripheral blood mononuclear cells infected
      with HIV-1 were similar to that in uninfected PBMCs, and approximately equivalent
      intracellular concentrations of GS-9148-DP and tenofovir (TVF)-DP were required
      to inhibit viral replication by 90%. Once it was formed, GS-9148-DP was
      efficiently retained in activated CD4(+) cells, with a half-life of 19 h. In
      addition, GS-9131 showed a low potential for drug interactions with other adenine
      nucleoside/nucleotide reverse transcriptase inhibitors, based on the lack of
      competition for anabolism between suprapharmacologic concentrations of GS-9148
      and TVF and the lack of activity of GS-9131 metabolites against purine nucleoside
      phosphorylase, an enzyme involved in the clearance of 2',3'-dideoxyinosine.
      Together, these observations elucidate the cellular pharmacology of GS-9131 and
      illustrate its efficient loading of lymphoid cells, resulting in a prolonged
      intracellular exposure to the active metabolite GS-9148-DP.

PMID- 18056283
TI  - Plasmid-mediated carbapenem-hydrolyzing beta-lactamase KPC-2 in Klebsiella
      pneumoniae isolate from Greece.

PMID- 18056282
TI  - Design and profiling of GS-9148, a novel nucleotide analog active against
      nucleoside-resistant variants of human immunodeficiency virus type 1, and its
      orally bioavailable phosphonoamidate prodrug, GS-9131.
AB  - GS-9148 [(5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2
      yloxymethyl)phosphonic acid] is a novel ribose-modified human immunodeficiency
      virus type 1 (HIV-1) nucleotide reverse transcriptase (RT) inhibitor (NRTI)
      selected from a series of nucleoside phosphonate analogs for its favorable in
      vitro biological properties including (i) a low potential for mitochondrial
      toxicity, (ii) a minimal cytotoxicity in renal proximal tubule cells and other
      cell types, (iii) synergy in combination with other antiretrovirals, and (iv) a
      unique resistance profile against multiple NRTI-resistant HIV-1 strains. Notably,
      antiviral resistance analysis indicated that neither the K65R, L74V, or M184V RT
      mutation nor their combinations had any effect on the antiretroviral activity of
      GS-9148. Viruses carrying four or more thymidine analog mutations showed a
      substantially smaller change in GS-9148 activity relative to that observed with
      most marketed NRTIs. GS-9131, an ethylalaninyl phosphonoamidate prodrug designed
      to maximize the intracellular delivery of GS-9148, is a potent inhibitor of
      multiple subtypes of HIV-1 clinical isolates, with a mean 50% effective
      concentration of 37 nM. Inside cells, GS-9131 is readily hydrolyzed to GS-9148,
      which is further phosphorylated to its active diphosphate metabolite (A. S. Ray,
      J. E. Vela, C. G. Boojamra, L. Zhang, H. Hui, C. Callebaut, K. Stray, K.-Y. Lin,
      Y. Gao, R. L. Mackman, and T. Cihlar, Antimicrob. Agents Chemother. 52:648-654,
      2008). GS-9148 diphosphate acts as a competitive inhibitor of RT with respect to
      dATP (K(i) = 0.8 muM) and exhibits low inhibitory potency against host
      polymerases including DNA polymerase gamma. Oral administration of GS-9131 to
      beagle dogs at a dose of 3 mg/kg of body weight resulted in high and persistent
      levels of GS-9148 diphosphate in peripheral blood mononuclear cells (with a
      maximum intracellular concentration of >9 microM and a half-life of >24 h). This
      favorable preclinical profile makes GS-9131 an attractive clinical development
      candidate for the treatment of patients infected with NRTI-resistant HIV.

PMID- 18056284
TI  - Analysis of the beta-tubulin gene from Vittaforma corneae suggests benzimidazole
      resistance.
AB  - We amplified, cloned, and sequenced the beta-tubulin gene of Vittaforma corneae,
      a microsporidium causing human infections. The beta-tubulin gene sequence has a
      substitution at Glu(198) (with glutamine), which is one of six amino acids
      reported to be associated with benzimidazole sensitivity. Benzimidazoles were
      assayed for antimicrosporidial activity and showed poor parasite inhibition.

PMID- 18056285
TI  - Multidrug transporters CaCdr1p and CaMdr1p of Candida albicans display different
      lipid specificities: both ergosterol and sphingolipids are essential for
      targeting of CaCdr1p to membrane rafts.
AB  - In this study, we compared the effects of altered membrane lipid composition on
      the localization of two membrane drug transporters from different superfamilies
      of the pathogenic yeast Candida albicans. We demonstrated that in comparison to
      the major facilitator superfamily multidrug transporter CaMdr1p, ATP-binding
      cassette transporter CaCdr1p of C. albicans is preferentially localized within
      detergent-resistant membrane (DRM) microdomains called 'rafts.' Both CaCdr1p and
      CaMdr1p were overexpressed as green fluorescent protein (GFP)-tagged proteins in
      a heterologous host Saccharomyces cerevisiae, wherein either sphingolipid
      (Deltasur4 or Deltafen1 or Deltaipt1) or ergosterol (Deltaerg24 or Deltaerg6 or
      Deltaerg4) biosynthesis was compromised. CaCdr1p-GFP, when expressed in the above
      mutant backgrounds, was not correctly targeted to plasma membranes (PM), which
      also resulted in severely impaired drug resistance. In contrast, CaMdr1p-GFP
      displayed no sorting defect in the mutant background and remained properly
      surface localized and displayed no change in drug resistance. Our data clearly
      show that CaCdr1p is selectively recruited, over CaMdr1p, to the DRM microdomains
      of the yeast PM and that any imbalance in the raft lipid constituents results in
      missorting of CaCdr1p.

PMID- 18056286
TI  - Bronchial smooth muscle remodeling involves calcium-dependent enhanced
      mitochondrial biogenesis in asthma.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are characterized by
      different patterns of airway remodeling, which all include an increased mass of
      bronchial smooth muscle (BSM). A remaining major question concerns the mechanisms
      underlying such a remodeling of BSM. Because mitochondria play a major role in
      both cell proliferation and apoptosis, we hypothesized that mitochondrial
      activation in BSM could play a role in this remodeling. We describe that both the
      mitochondrial mass and oxygen consumption were higher in the BSM from asthmatic
      subjects than in that from both COPD and controls. This feature, which is
      specific to asthma, was related to an enhanced mitochondrial biogenesis through
      up-regulation of peroxisome proliferator-activated receptor gamma coactivator
      (PGC)-1alpha, nuclear respiratory factor-1, and mitochondrial transcription
      factor A. The priming event of such activation was an alteration in BSM calcium
      homeostasis. BSM cell apoptosis was not different in the three groups of
      subjects. Asthmatic BSM was, however, characterized by increased cell growth and
      proliferation. Both characteristics were completely abrogated in mitochondria
      deficient asthmatic BSM cells. Conversely, in both COPD and control BSM cells,
      induction of mitochondrial biogenesis reproduced these characteristics. Thus, BSM
      in asthmatic patients is characterized by an altered calcium homeostasis that
      increases mitochondrial biogenesis, which, in turn, enhances cell proliferation,
      leading to airway remodeling.

PMID- 18056287
TI  - Multiple, conserved cryptic recombination signals in VH gene segments: detection
      of cleavage products only in pro B cells.
AB  - Receptor editing is believed to play the major role in purging newly formed B
      cell compartments of autoreactivity by the induction of secondary V(D)J
      rearrangements. In the process of immunoglobulin heavy (H) chain editing, these
      secondary rearrangements are mediated by direct V(H)-to-J(H) joining or cryptic
      recombination signals (cRSs) within V(H) gene segments. Using a statistical model
      of RS, we have identified potential cRSs within V(H) gene segments at conserved
      sites flanking complementarity-determining regions 1 and 2. These cRSs are active
      in extrachromosomal recombination assays and cleaved during normal B cell
      development. Cleavage of multiple V(H) cRSs was observed in the bone marrow of
      C57BL/6 and RAG2:GFP and microMT congenic animals, and we determined that cRS
      cleavage efficiencies are 30-50-fold lower than a physiological RS. cRS signal
      ends are abundant in pro-B cells, including those recovered from microMT mice,
      but undetectable in pre- or immature B cells. Thus, V(H) cRS cleavage regularly
      occurs before the generation of functional preBCR and BCR. Conservation of cRSs
      distal from the 3' end of V(H) gene segments suggests a function for these
      cryptic signals other than V(H) gene replacement.

PMID- 18056290
TI  - Assessment of children's health-related quality of life in the United States with
      a multidimensional index.
AB  - OBJECTIVE: Using nationally representative data, we examined biological, medical
      system, and sociodemographic factors that are associated with health-related
      quality of life as measured by a multidimensional index that accounts for a wide
      range of child health domains. METHODS: Children aged > or = 6 years (N = 69,031)
      were drawn from the 2003/2004 National Survey of Children's Health. A random 25%
      sample was used to create a 12-item index of health-related quality of life with
      a range of 0 to 100, based on the conceptual framework of the Child Health and
      Illness Profile. Bivariate and multivariable regression analyses were conducted
      to identify the unadjusted and independent associations of key biological,
      medical system, and sociodemographic variables with health-related quality of
      life. RESULTS: The index mean was 72.3 (SD: 14.5), median value was 73.7, and
      range was 11.1 to 99.9. Only 0.2% of children had a score at the ceiling. In
      multivariable regression analysis, the following variables were independently
      associated with lower health-related quality of life: biological factors (greater
      disease burden, severe asthma, and overweight status); medical system factors
      (unmet medical needs, lack of a regular health care provider, Medicaid insurance,
      or being uninsured previously during the year); and sociodemographic factors
      (older age groups, lower family education, single-mother family, having a smoker
      in the household, black race, and poverty). CONCLUSIONS: Health-related quality
      of life in the United States is poorest for children and youth in lower
      socioeconomic status groups, those with access barriers, adolescents compared
      with children, and individuals with medical conditions. A multidimensional health
      related quality-of-life index is an alternative to conventional measures (eg,
      mortality) for national monitoring of child health.

PMID- 18056288
TI  - Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal
      surface protein causing calcium influx and apoptosis.
AB  - The interesting observation was made 20 years ago that psychotic manifestations
      in patients with systemic lupus erythematosus are associated with the production
      of antiribosomal-P protein (anti-P) autoantibodies. Since then, the pathogenic
      role of anti-P antibodies has attracted considerable attention, giving rise to
      long-term controversies as evidence has either contradicted or confirmed their
      clinical association with lupus psychosis. Furthermore, a plausible mechanism
      supporting an anti-P-mediated neuronal dysfunction is still lacking. We show that
      anti-P antibodies recognize a new integral membrane protein of the neuronal cell
      surface. In the brain, this neuronal surface P antigen (NSPA) is preferentially
      distributed in areas involved in memory, cognition, and emotion. When added to
      brain cellular cultures, anti-P antibodies caused a rapid and sustained increase
      in calcium influx in neurons, resulting in apoptotic cell death. In contrast,
      astrocytes, which do not express NSPA, were not affected. Injection of anti-P
      antibodies into the brain of living rats also triggered neuronal death by
      apoptosis. These results demonstrate a neuropathogenic potential of anti-P
      antibodies and contribute a mechanistic basis for psychiatric lupus. They also
      provide a molecular target for future exploration of this and other psychiatric
      diseases.

PMID- 18056289
TI  - Chromosomal position of a VH gene segment determines its activation and
      inactivation as a substrate for V(D)J recombination.
AB  - Complete IgHC gene rearrangement occurs only in B cells in a stage-specific and
      ordered manner. We used gene targeting to reposition a distal V(H) gene segment
      to a region just 5' of the D(H) gene cluster and found its activation to be
      highly dependent on the chromosomal domain within which it resides. The targeted
      V(H) gene segment rearranged at a higher frequency than its endogenous
      counterpart, its rearrangement was no longer ordered, and its ability to be
      silenced by allelic exclusion was lost. Additionally, the targeted V(H) gene
      segment lost lineage specificity, as VDJ(H) rearrangement was observed in
      thymocytes. These data suggest that locus contraction, mimicked by proximal
      targeting, can override any regulation imposed by DNA sequences immediately
      surrounding V(H) gene segments.

PMID- 18056291
TI  - Quality medical homes: meeting children's needs for therapeutic and supportive
      services.
AB  - OBJECTIVE: The objective of this study was to determine whether the quality of a
      medical home is associated with access to needed therapeutic and supportive
      services among children with special health care needs. METHODS: Data from the
      2000-2001 National Survey of Children With Special Health Care Needs were used in
      the analysis. The primary group of interest was children who were 0 to 17 years
      of age and needed therapeutic (n = 15,793) or supportive (n = 23,376) services.
      For each characteristic of a quality medical home, the percentage of children who
      needed and received therapeutic and supportive services was generated. Logistic
      regression was used to control for covariates while modeling the association
      between overall quality of a child's medical home and having unmet needs for
      therapeutic or supportive services. RESULTS: Of all children identified as
      needing services, 16.2% had unmet therapeutic and 9.8% unmet supportive service
      needs. Only 23.9% of the children who needed therapeutic and 32.5% of children
      who needed supportive services met the criteria of having a quality medical home.
      High-quality care within medical homes was associated with a decreased likelihood
      of having unmet needs for therapeutic and supportive services. Each
      characteristic of a quality medical home was associated with unmet need, as were
      severity of the child's condition, family income of <200% of the federal poverty
      level, underinsurance, and maternal education beyond high school. CONCLUSIONS:
      Among other factors, having a poor-quality medical home seems to be a barrier to
      receiving needed therapeutic or supportive services for children with special
      health care needs. Efforts on the part of pediatricians to establish quality
      medical homes for all children could have the added benefit of facilitating
      access to needed therapeutic and supportive services and promoting the health and
      well-being of children with special health care needs and their families.

PMID- 18056292
TI  - Cultural competence in the college biology classroom.

PMID- 18056294
TI  - Metagenomics: a call for bringing a new science into the classroom (while it's
      still new).

PMID- 18056295
TI  - Realms of the viruses online.

PMID- 18056296
TI  - H. Craig Heller. Interviewed by Laura L. Mays Hoopes.

PMID- 18056297
TI  - Building, using, and maximizing the impact of concept inventories in the
      biological sciences: report on a National Science Foundation sponsored conference
      on the construction of concept inventories in the biological sciences.
AB  - The meeting "Conceptual Assessment in the Biological Sciences" was held March 3
      4, 2007, in Boulder, Colorado. Sponsored by the National Science Foundation and
      hosted by University of Colorado, Boulder's Biology Concept Inventory Team, the
      meeting drew together 21 participants from 13 institutions, all of whom had
      received National Science Foundation funding for biology education. Topics of
      interest included Introductory Biology, Genetics, Evolution, Ecology, and the
      Nature of Science. The goal of the meeting was to organize and leverage current
      efforts to develop concept inventories for each of these topics. These diagnostic
      tools are inspired by the success of the Force Concept Inventory, developed by
      the community of physics educators to identify student misconceptions about
      Newtonian mechanics. By working together, participants hope to lessen the risk
      that groups might develop competing rather than complementary inventories.

PMID- 18056298
TI  - Stem cell biology should be taught in high schools.

PMID- 18056299
TI  - Keeping it real: substantive learning on a short calendar.
AB  - Many institutions offer courses that last less than a quarter and are a student's
      sole academic responsibility for that short term. There is an unfortunate and
      incorrect perception that such short classes cannot be used to teach
      substantively. At Colorado College, we teach all of our courses in 3.5 wk,
      including majors' courses in molecular cell biology and related fields. The
      article presents strategies for exploiting short terms as excellent venues for
      deep learning in the biological sciences.

PMID- 18056300
TI  - Grappling with the literature of education research and practice.
AB  - The absence of a central database and use of specialized language hinder
      nonexperts in becoming familiar with the science teaching and learning literature
      and using it to inform their work. The challenge of locating articles related to
      a specific question or problem, coupled with the difficulty of comprehending
      findings based on a variety of different perspectives and practices, can be
      prohibitively difficult. As I have transitioned from bench to classroom-based
      research, I have become familiar with how to locate, decipher, and evaluate the
      education research literature. In this essay, I point out analogies to the
      literature of science research and practice, and I reference some of the
      literature that I have found useful in becoming an education researcher. I also
      introduce a new regular feature, "Current Insights: Recent Research in Science
      Teaching and Learning," which is designed to point CBE--Life Sciences Education
      (CBE-LSE) readers to current articles of interest in life sciences education, as
      well as more general and noteworthy publications in education research.

PMID- 18056301
TI  - Undergraduate research experiences support science career decisions and active
      learning.
AB  - The present study examined the reliability of student evaluations of summer
      undergraduate research experiences using the SURE (Survey of Undergraduate
      Research Experiences) and a follow-up survey disseminated 9 mo later. The survey
      further examines the hypothesis that undergraduate research enhances the
      educational experience of science undergraduates, attracts and retains talented
      students to careers in science, and acts as a pathway for minority students into
      science careers. Undergraduates participated in an online survey on the benefits
      of undergraduate research experiences. Participants indicated gains on 20
      potential benefits and reported on career plans. Most of the participants began
      or continued to plan for postgraduate education in the sciences. A small group of
      students who discontinued their plans for postgraduate science education reported
      significantly lower gains than continuing students. Women and men reported
      similar levels of benefits and similar patterns of career plans. Undergraduate
      researchers from underrepresented groups reported higher learning gains than
      comparison students. The results replicated previously reported data from this
      survey. The follow-up survey indicated that students reported gains in
      independence, intrinsic motivation to learn, and active participation in courses
      taken after the summer undergraduate research experience.

PMID- 18056302
TI  - Using Saccharomyces cerevisiae to test the mutagenicity of household compounds:
      an open ended hypothesis-driven teaching lab.
AB  - In our Fundamentals of Genetics lab, students perform a wide variety of labs to
      reinforce and extend the topics covered in lecture. I developed an active
      learning lab to augment the lecture topic of mutagenesis. In this lab exercise,
      students determine if a compound they bring from home is a mutagen. Students are
      required to read extensive background material, perform research to find a
      potential mutagen to test, develop a hypothesis, and bring to the lab their own
      suspected mutagen. This lab uses a specially developed strain of Saccharomyces
      cerevisiae, D7, to determine if a compound is a mutagen. Mutagenesis of the D7
      genome can lead to a scorable alteration in the phenotypes of this strain.
      Students outline and carry out a protocol for treatment of the yeast tester
      strain, utilizing the concept of dose/response and positive and negative
      controls. Students report on their results using a PowerPoint presentation to
      simulate giving a scientific presentation. The students' self-assessment of their
      knowledge indicated that, in all cases, the students felt that they knew more
      about the assay, mutagenesis, and the relationship between genotype and phenotype
      (P < 0.05) after completing the exercise.

PMID- 18056303
TI  - Identifying future scientists: predicting persistence into research training.
AB  - This study used semistructured interviews and grounded theory to look for
      characteristics among college undergraduates that predicted persistence into
      Ph.D. and M.D./Ph.D. training. Participants in the summer undergraduate and
      postbaccalaureate research programs at the Mayo Clinic College of Medicine were
      interviewed at the start, near the end, and 8-12 months after their research
      experience. Of more than 200 themes considered, five characteristics predicted
      those students who went on to Ph.D. and M.D./Ph.D. training or to M.D. training
      intending to do research: 1) Curiosity to discover the unknown, 2) Enjoyment of
      problem solving, 3) A high level of independence, 4) The desire to help others
      indirectly through research, and 5) A flexible, minimally structured approach to
      the future. Web-based surveys with different students confirmed the high
      frequency of curiosity and/or problem solving as the primary reason students
      planned research careers. No evidence was found for differences among men, women,
      and minority and nonminority students. Although these results seem logical
      compared with successful scientists, their constancy, predictive capabilities,
      and sharp contrast to students who chose clinical medicine were striking. These
      results provide important insights into selection and motivation of potential
      biomedical scientists and the early experiences that will motivate them toward
      research careers.

PMID- 18056304
TI  - A semester-long student-directed research project involving enzyme immunoassay:
      appropriate for immunology, endocrinology, or neuroscience courses.
AB  - The following project aimed at promoting integrated and long-lasting learning is
      described for an Immunology course, but it may be adapted to other disciplines.
      Students were asked to develop and carry out a research project to examine the
      relationship between immune function and stress. The experiments were required to
      include the assessment of salivary cortisol and salivary IgA (sIgA) with enzyme
      immunoassays. All other aspects of the experiments were developed by student
      groups with appropriate guidance from the instructor. Data are presented for one
      group project that assessed the effect of music on cortisol and sIgA. Overall
      levels of sIgA and cortisol were consistent with reported values. Students found
      a significant decrease in cortisol over time. Additionally, there was a trend
      that supported the overall student hypothesis regarding the effect of stress and
      immune function. Compared with the same Immunology course that included an
      instructor-designed experiment using enzyme immunoassays for cortisol and sIgA,
      several assessments (e.g., final grades and comments on student evaluations) show
      that overall learning seemed to be much better in the course with the student
      directed research project.

PMID- 18056305
TI  - A new paradigm for mentored undergraduate research in molecular microbiology.
AB  - Science educators agree that an undergraduate research experience is critical for
      students who are considering graduate school or research careers. The process of
      researching a topic in the primary literature, designing experiments,
      implementing those experiments, and analyzing the results is essential in
      developing the analytical skills necessary to become a true scientist. Because
      training undergraduates who will only be in the laboratory for a short period is
      time consuming for faculty mentors, many students are unable to find appropriate
      research opportunities. We hypothesized that we could effectively mentor several
      students simultaneously, using a method that is a hybrid of traditional
      undergraduate research and a traditional laboratory course. This article
      describes a paradigm for mentored undergraduate research in molecular
      microbiology where students have ownership of their individual projects, but the
      projects are done in parallel, enabling the faculty mentor to guide multiple
      students efficiently.

PMID- 18056306
TI  - The annotated bibliography and citation behavior: enhancing student scholarship
      in an undergraduate biology course.
AB  - Contemporary undergraduates in the biological sciences have unprecedented access
      to scientific information. Although many of these students may be savvy
      technologists, studies from the field of library and information science
      consistently show that undergraduates often struggle to locate, evaluate, and use
      high-quality, reputable sources of information. This study demonstrates the
      efficacy and pedagogical value of a collaborative teaching approach designed to
      enhance information literacy competencies among undergraduate biology majors who
      must write a formal scientific research paper. We rely on the triangulation of
      assessment data to determine the effectiveness of a substantial research paper
      project completed by students enrolled in an upper-level biology course. After
      enhancing library-based instruction, adding an annotated bibliography
      requirement, and using multiple assessment techniques, we show fundamental
      improvements in students' library research abilities. Ultimately, these
      improvements make it possible for students to more independently and effectively
      complete this challenging science-based writing assignment. We document critical
      information literacy advances in several key areas: student source-type use,
      annotated bibliography enhancement, plagiarism reduction, as well as student and
      faculty/librarian satisfaction.

PMID- 18056308
TI  - A correction: how I fixed my mistake.

PMID- 18056310
TI  - Using a sledgehammer to crack a walnut: the modern management of concussion.

PMID- 18056311
TI  - An international review of head and spinal cord injuries in alpine skiing and
      snowboarding.
AB  - BACKGROUND: Alpine skiing and snowboarding are popular winter activities
      worldwide, enjoyed by participants of all ages and skill levels. There is some
      evidence that the incidence of traumatic brain injury (TBI) and spinal cord
      injury (SCI) in these activities may be increasing. These injuries can cause
      death or severe debilitation, both physically and emotionally, and also result in
      enormous financial burden to society. Indeed, TBI is the leading cause of death
      and catastrophic injury in the skiing and snowboarding population. Furthermore,
      there are severe limitations to therapeutic interventions to restore neurological
      function after TBI and SCI, and thus the emphasis must be on prevention.
      OBJECTIVES: (1) To examine the worldwide epidemiology of TBI and SCI in skiing
      and snowboarding; (2) to describe and examine the effectiveness of prevention
      strategies to reduce the incidence of TBI and SCI in skiing and snowboarding.
      SEARCH STRATEGY: Searches were performed on a variety of databases to identify
      articles relevant to catastrophic central nervous system injury in skiing and
      snowboarding. The databases included PubMed, Medline, EMBASE, CDSR, ACP Journal
      Club, DARE, CCTR, SportDiscus, CINAHL, and Advanced Google searches. SELECTION
      CRITERIA AND DATA COLLECTION: After initial prescreening, articles included in
      the review required epidemiological data on SCI, TBI, or both. Articles had to be
      directly associated with the topic of skiing and/or snowboarding and published
      between January 1990 and December 2004. RESULTS: 24 relevant articles, from 10
      different countries, were identified. They indicate that the incidence of TBI and
      SCI in skiing and snowboarding is increasing. The increases coincide with the
      development and acceptance of acrobatic and high-speed activities on the
      mountains. There is evidence that helmets reduce the risk of head injury by 22
      60%. Head injuries are the most common cause of death among skiers and
      snowboarders, and young male snowboarders are especially at risk of death from
      head injury. CONCLUSIONS: There should be enhanced promotion of injury prevention
      that includes the use of helmets and emphasizes the skier's and snowboarder's
      responsibility code.

PMID- 18056312
TI  - Personality factors as predictors of persistent risky driving behavior and crash
      involvement among young adults.
AB  - OBJECTIVES: The aim of this study was to examine the relationship between
      personality factors assessed during adolescence and persistent risky driving
      behavior and traffic crash involvement among young adults. DESIGN: Data for this
      investigation were drawn from the Dunedin Multidisciplinary Health and
      Development Study, a longitudinal study of a cohort born in Dunedin, New Zealand.
      SUBJECTS: The study population was 1037 young people born between 1 April 1972
      and 31 March 1973. MAIN OUTCOME MEASURES: The main outcome measures were
      persistent risky driving behaviors and crash involvement, collected in a face-to
      face road-safety interview at ages 21 and 26. RESULTS: The only outcomes for
      which there were sufficient numbers of females were a driver involved in any
      crash and a driver involved in an injury crash. Univariate logistic regression
      revealed that there were no significant predictors for either of these outcomes.
      For the males, at the univariate level, aggression, traditionalism, and
      alienation were the personality scales most frequently associated with risky
      driving behavior and crash risk. After adjusting for driving exposure, only high
      levels of aggression predicted being a driver involved in a crash, and alienation
      predicted being a driver involved in an injury crash. CONCLUSION: These results
      suggest that road-safety interventions seeking to deter young adult males from
      persistent risky driving behavior need to be directed at those who do not endorse
      traditional views, are aggressive, and feel alienated from the rest of society.

PMID- 18056314
TI  - Association between road vehicle collisions and recent medical contact in older
      drivers: a case-crossover study.
AB  - OBJECTIVE: To estimate the association between past medical contacts and the risk
      of vehicle collision in a population of older drivers from the province of
      Quebec, Canada. DESIGN: Case-crossover study. SETTING: Quebec. PARTICIPANTS: 111
      699 older drivers involved in at least one vehicle collision between January 1988
      and December 2000. MAIN OUTCOME MEASURES: For each driver, the risk of having a
      vehicle collision while exposed and not exposed to a medical contact was
      compared. Separate conditional logistic regression analyses were conducted for
      all drivers and in four diagnostic-specific subgroups. RESULTS: The study found a
      weak but statistically significant increased risk of all collisions being
      associated with a medical contact within 1 month before the collision, for all
      drivers (OR=1.10, 95% CI 1.08 to 1.11) and for drivers with diabetes (OR=1.07,
      95% CI 1.03 to 1.11). CONCLUSION: Older drivers who have a collision are more
      likely to have been in contact with a physician shortly before the collision.
      These findings suggest that there might be an opportunity to detect medical
      conditions that put older drivers at higher risk of collision; however, further
      research is needed to assess the potential effectiveness and practical modalities
      of screening.

PMID- 18056315
TI  - Pattern of seat belt wearing in Nanjing, China.
AB  - OBJECTIVE: To describe the patterns of seat belt wearing in Nanjing, China for
      drivers, front seat passengers, and rear occupants of motor vehicles. DESIGN:
      Roadside observational study. SETTING: Four sites in central and northern Nanjing
      during daylight hours over 1 week in April 2005. SUBJECTS: Drivers and passengers
      of 17 147 cars, taxis, goods vans, and pickups, which traveled in the inside
      traffic lane. MAIN OUTCOME MEASURES: Percentage seat belt wearing for each of
      seating position, age/sex, time of day, vehicle type, day of week. RESULTS: The
      rate of seat belt wearing was significantly higher in drivers (67.3%, 95% CI 66.6
      to 68.0) than front seat passengers (18.9%, 95% CI, 18.0 to 19.8). It was
      negligible for second front seat passengers (2.6%, 95% CI 0.3 to 4.9) and rear
      seat passengers (0.5%, 95% CI 0.3 to 0.7). Belt tampering, such that protection
      would be reduced in the event of a crash, was observed for 18.5% of taxi drivers.
      Drivers were most likely to wear seat belts in cars and vans and at a city
      roundabout; front seat passengers were most likely to wear seat belts in non-taxi
      vehicles, during the evening rush hour, if the driver was wearing a belt, and on
      the local north road. Drivers were least likely to wear a belt in the early
      morning, in pickups and taxis, on Tuesday (or the following week), and on the
      local north road; front seat passengers were least likely to wear a belt in taxis
      and if the driver was not wearing a belt. CONCLUSIONS: Rates of seat belt wearing
      by passengers were low despite national legislation and provincial regulations
      coming into effect several months before the survey. Combined education and
      enforcement are necessary accompaniments to legislation.

PMID- 18056316
TI  - Understanding high traffic injury risks for children in low socioeconomic areas:
      a qualitative study of parents' views.
AB  - OBJECTIVE: To gain an in-depth qualitative understanding of parents' views about
      their children's exposure to road traffic injury risk in low socioeconomic areas.
      DESIGN: Focus groups facilitated by a moderator with content analysis of data.
      SETTING: Focus groups were conducted in 10 low socioeconomic English districts
      that also have high rates of child pedestrian injury. Research was conducted in
      community venues within each area. SUBJECTS: Parents of children aged 9-14 years
      living in low socioeconomic areas. RESULTS: Parents believe that children play in
      their local streets for the following reasons: they like playing out with friends
      near home; there are few safe, secure, and well-maintained public spaces for
      children; children are excluded from affordable leisure venues because of their
      costs; insufficient parental responsibility. For children that play in the
      street, the key sources of risk identified by parents were: illegal riding and
      driving around estates and on the pavements; the speed and volume of traffic;
      illegal parking; drivers being poorly informed about where children play;
      children's risk-taking behavior. CONCLUSIONS: Intervention programs need to take
      into account multiple reasons why children in low socioeconomic areas become
      exposed to hazardous environments thereby increasing their risk of injury. Multi
      agency partnerships involving the community are increasingly needed to implement
      traditional road safety approaches, such as education, engineering, and
      enforcement, and provide safe and accessible public space, affordable activities
      for children, and greater support for parents.

PMID- 18056317
TI  - Car safety seats for children: rear facing for best protection.
AB  - OBJECTIVE: To compare the injury risk between rear-facing (RFCS) and forward
      facing (FFCS) car seats for children less than 2 years of age in the USA.
      METHODS: Data were extracted from a US National Highway Traffic Safety
      Administration vehicle crash database for the years 1988-2003. Children 0-23
      months of age restrained in an RFCS or FFCS when riding in passenger cars, sport
      utility vehicles, or light trucks were included in the study. Logistic regression
      models and restraint effectiveness calculations were used to compare the risk of
      injury between children restrained in RFCSs and FFCSs. RESULTS: Children in FFCSs
      were significantly more likely to be seriously injured than children restrained
      in RFCSs in all crash types (OR=1.76, 95% CI 1.40 to 2.20). When considering
      frontal crashes alone, children in FFCSs were more likely to be seriously injured
      (OR=1.23), although this finding was not statistically significant (95% CI 0.95
      to 1.59). In side crashes, however, children in FFCSs were much more likely to be
      injured (OR=5.53, 95% CI 3.74 to 8.18). When 1 year olds were analyzed
      separately, these children were also more likely to be seriously injured when
      restrained in FFCSs (OR=5.32, 95% CI 3.43 to 8.24). Effectiveness estimates for
      RFCSs (93%) were found to be 15% higher than those for FFCSs (78%). CONCLUSIONS:
      RFCSs are more effective than FFCSs in protecting restrained children aged 0-23
      months. The same findings apply when 1 year olds are analyzed separately. Use of
      an RFCS, in accordance with restraint recommendations for child size and weight,
      is an excellent choice for optimum protection up to a child's second birthday.

PMID- 18056318
TI  - Maternal depression, child behavior, and injury.
AB  - BACKGROUND: Few data exist on the effect of maternal depression on child injury
      outcomes and mediators of this relationship. OBJECTIVE: To examine the
      relationship between mothers' depressive symptoms and medically attended injuries
      in their children and the potential mediating role of child behavior.
      DESIGN/METHODS: A cohort of mother-child dyads from the National Longitudinal
      Study of Youth followed from 1992 to 1994. The primary exposure variable was
      maternal depressive symptoms as measured by the Center for Epidemiologic Studies
      Depression Scale in 1992. Child behavior was assessed by the Behavior Problems
      Index externalizing subscale. Logistic regression was used to examine the
      relationship between depressive symptoms, child behavior, and injury reported in
      the prior year in 1994. RESULTS: 94 medically attended injuries were reported in
      the 1106 children (8.5%); two-thirds were sustained in the home environment.
      Maternal depressive symptoms significantly increased the risk of child injury;
      injury risk increased 4% for every 1-point increase in depressive symptoms
      (adjusted OR 1.04, 95% CI 1.01 to 1.08, p=0.02). Increasing maternal depressive
      symptoms also increased the risk of externalizing behavior problems (adjusted OR
      1.06, 95% CI 1.03 to 1.09), but externalizing behavior problems did not
      significantly mediate the relationship between maternal symptoms and child
      injury. CONCLUSIONS: Increasing depressive symptoms in mothers was associated
      with an increased risk of child injury. Child behavior did not significantly
      mediate the association between maternal depressive symptoms and child injury in
      this cohort. Greater recognition, referral, and treatment of depressive symptoms
      in mothers may have effects on child behavior and injury risk.

PMID- 18056319
TI  - Work practices and childhood agricultural injury.
AB  - OBJECTIVE: To evaluate whether children's agricultural work practices were
      associated with agricultural injury and to identify injury and work practice
      predictors. DESIGN: Analyses were based on nested case-control data collected by
      the Regional Rural Injury Study-II (RRIS-II) surveillance study in 1999 and 2001
      by computer-assisted telephone interviews. SUBJECTS: Cases (n=425) and controls
      (n=1886) were persons younger than 20 years of age from Midwestern agricultural
      households. Those reporting agricultural injuries became cases; controls (no
      injury) were selected using incidence density sampling. MAIN OUTCOME MEASURES:
      Multivariate logistic regression was used to estimate the risks of injury
      associated with agricultural work, performing chores earlier than developmentally
      appropriate, hours worked per week, and number of chores performed. RESULTS:
      Increased risks of injury were observed for children who performed chores 2-3
      years younger than recommended, compared to being "age-appropriate" (odds ratio
      (OR)=2.6, 95% confidence interval (CI)=1.4-4.5); performed any agricultural work
      (3.9 (2.6-5.6)); performed seven to ten chores per month compared to one chore
      (2.2 (1.3-3.5)); and worked 11-30 or 31-40 h per week compared to 1-10 h (1.6
      (1.2-2.1) and 2.2 (1.3-3.7), respectively). Decreased risks of injury were
      observed for non-working children compared to children performing what are
      commonly considered safe levels of agricultural work. CONCLUSIONS: This study
      demonstrated elevated risks of agricultural injury among children who perform
      developmentally inappropriate chores. Results suggest that the efficacy of age
      restrictions for preventing the occurrence of childhood agricultural injuries
      warrants further evaluation.

PMID- 18056321
TI  - Completeness and accuracy of International Classification of Disease (ICD)
      external cause of injury codes in emergency department electronic data.
AB  - The accuracy of external cause of injury codes (E codes) for work-related and non
      work-related injuries in Massachusetts emergency department data were evaluated.
      Medical records were reviewed and coded by a nosologist with expertise in E
      coding for a stratified random sample of 1000 probable work-related (PWR) and 250
      probable non-work-related (PNWR) cases. Cause of injury E codes were present for
      98% of reviewed cases and accurate for 65% of PWR cases and 57% of PNWR cases.
      Place of occurrence E codes were present in less than 30% of cases. Broad cause
      of injury categories were accurate for about 85% of cases. Non-specific
      categories (not elsewhere classified, not specified) accounted for 34% of broad
      category misclassifications. Among specified causes, machinery injuries were
      misclassified most often (39/60, 65%), predominantly as cut/pierce or struck
      by/against. E codes reliably identify the broad mechanism of injury, but
      inaccuracies and incompleteness suggest areas for training of hospital admissions
      staff, providers, and coders.

PMID- 18056320
TI  - Cost of injuries from a prospective cohort study of North Carolina high school
      athletes.
AB  - OBJECTIVE: To estimate the economic cost of injuries in a population of US high
      school varsity athletes. DESIGN AND SETTING: The North Carolina High School
      Athletic Injury Study, conducted from 1996 to 1999, was a prospective cohort
      study of injury incidence and severity. A two-stage cluster sampling technique
      was used to select athletic teams from 100 high schools in North Carolina. An
      injury cost model was used to estimate the economic cost of injury. PARTICIPANTS:
      Varsity athletes from 12 sports: football, girls' and boy's soccer, girls' and
      boys' track, girls' and boy's basketball, baseball, softball, wrestling,
      volleyball, and cheerleading. MAIN OUTCOME MEASURES: Descriptive data were
      collected at the time of injury. Three types of costs were estimated: medical,
      human capital (medical costs plus loss of future earnings), and comprehensive
      (human capital costs plus lost quality of life). RESULTS: The annual statewide
      estimates were $9.9 million in medical costs, $44.7 million in human capital
      costs, and $144.6 million in comprehensive costs. The mean medical cost was $709
      per injury (95% CI $542 to $927), $2223 per injury (95% CI $1709 to $2893) in
      human capital costs, and $10,432 per injury (95% CI $8062 to $13,449) in
      comprehensive costs. Sport and competition division were significant predictors
      of injury costs. CONCLUSIONS: Injuries among high school athletes represent a
      significant economic cost to society. Further research should estimate costs in
      additional populations to begin to develop cost-effective sports injury
      prevention programs.

PMID- 18056322
TI  - Family fun--family tragedy: ATV-related deaths involving family members.

PMID- 18056323
TI  - Recognizing the importance of injury in other policy forums: the case of
      motorcycle licensing policy in Spain.

PMID- 18056327
TI  - Advocating for PET/CT.

PMID- 18056324
TI  - Survey of patient release information on radiation and security checkpoints.

PMID- 18056329
TI  - "Focus on molecular imaging".

PMID- 18056330
TI  - Comparison of imaging techniques for tracking cardiac stem cell therapy.

PMID- 18056331
TI  - PET/CT in evaluating pediatric malignancies: a clinician's perspective.

PMID- 18056332
TI  - 18F-FDG PET/CT in evaluating non-CNS pediatric malignancies.
AB  - We reviewed our experience of (18)F-FDG PET/CT in noncentral nervous system (CNS)
      pediatric malignancies and evaluated if PET/CT provided additional information to
      conventional imaging (CI) examinations to determine the efficacy of this new
      imaging modality in the clinical setting. METHODS: One-hundred fifty-one
      consecutive FDG PET/CT examinations in 55 pediatric patients with non-CNS
      malignant tumors were reviewed. Among them, 108 PET/CT examinations were
      accompanied by CI, such as contrast CT or MRI, performed within a month of PET/CT
      in our hospital. Two radiologists reviewed the indication, purpose, and PET/CT
      findings and compared the findings with those of CI, if available, on the
      representative lesion in each of the 6 separate body regions. Positive findings
      included abnormal findings related to malignant lesions (suspected) as well as
      equivocal findings, in which the presence of malignancy could not be denied, but
      excluded findings considered to relate to past treatment. Accuracy of the
      findings was determined on the basis of the reference standard comprising
      histopathologic findings or informative follow-up of >1 y. An examination-based
      analysis was also performed in terms of additional information of PET/CT to CI.
      RESULTS: There were 56 PET/CT-positive-CI-positive, 26 PET/CT-positive-CI
      negative, and 54 PET/CT-negative-CI-positive lesions in 108 PET/CT examinations
      accompanied by CI, of which 54, 20, and 52 exhibited accurate PET/CT findings,
      respectively. Seventeen of the 20 PET/CT true-positive-CI false-negative lesions
      represented small lymph nodes diagnosed as negative on CI. All 52 PET/CT true
      negative-CI false-positive findings were observed in lesions in a posttreatment
      status including 30 mediastinal masses in lymphoma. Examination-based analysis
      revealed that additional information of PET/CT to CI was found in 37 (34%) of the
      108 examinations: 23 (21%) as negative and 14 (13%) as positive PET/CT findings.
      CONCLUSION: PET/CT exhibited better diagnostic performance than CI and showed
      accurate findings in 90% (72/80) of lesions with discordant findings between
      them. Additional information of PET/CT to CI was observed in more than one third
      of examinations compared. PET/CT was demonstrated to be an accurate imaging
      modality in evaluating pediatric patients with non-CNS malignancies.

PMID- 18056333
TI  - Nuclear imaging in cardiac resynchronization therapy.
AB  - Recently, cardiac resynchronization therapy (CRT) has become implemented in the
      treatment of patients with severe heart failure. Although the improvement in
      systolic function after CRT implantation can be considerable, 20%-30% of patients
      do not respond to CRT. Evidence is accumulating that the presence of left
      ventricular (LV) dyssynchrony is mandatory for a response to CRT. Since the early
      1980s attempts have been made to assess cardiac dyssynchrony with nuclear
      imaging, and it has been reported recently that information on LV dyssynchrony
      can be obtained from gated myocardial perfusion SPECT with phase analysis. Other
      studies with SPECT have shown that extensive scar tissue will limit the response
      to CRT; similarly, it has been demonstrated that viable tissue (assessed with
      SPECT) in the target zone for the LV pacing lead (usually the lateral wall) is
      needed for a response to CRT. Moreover, studies with PET have provided insight
      into the changes in myocardial perfusion, metabolism, and efficiency after CRT.
      In the current review, a comprehensive summary is provided on the potential role
      of nuclear imaging in the selection of heart failure patients for CRT. The value
      of other imaging techniques is also addressed.

PMID- 18056334
TI  - L-3-11C-lactate as a PET tracer of myocardial lactate metabolism: a feasibility
      study.
AB  - Lactate is a key myocardial energy source. Lactate metabolism is altered in a
      variety of conditions, such as exercise and diabetes mellitus. However, to our
      knowledge, noninvasive quantitative measurements of myocardial lactate metabolism
      have never been performed because of the lack of an adequate radiotracer. In this
      study we tested L-3-(11)C-lactate ((11)C-lactate) as such a tracer. METHODS:
      Twenty-three dogs were studied under a wide range of metabolic interventions.
      (11)C-Lactate and (13)C-lactate were injected as boluses and PET data were
      acquired for 1 h. Concomitant arterial and coronary sinus (ART/CS) blood samples
      were collected to identify (13)C-lactate metabolites and to measure fractional
      myocardial extraction/production of (11)C metabolite fractions ((11)C acidic:
      (11)CO(2) and (11)C-lactate; (11)C basic: (11)C-labeled amino acids; and (11)C
      neutral: (11)C-glucose). Lactate metabolism was quantified using 2 PET
      approaches: monoexponential clearance analysis (oxidation only) and kinetic
      modeling of PET (11)C-myocardial curves. RESULTS: Arterial (11)C acidic, neutral,
      and basic metabolites were identified as primarily (11)C-labeled lactate +
      pyruvate, glucose, and alanine, respectively. Despite a significant contribution
      of (11)C-glucose (23%-45%) and (11)C-alanine (<11%) to total arterial (11)C
      activity, both were minimally extracted(+)/produced(-) by the heart (1.7% +/-
      1.0% and -0.12% +/- 0.84%, respectively). Whereas extraction of (11)C-lactate
      correlated nonlinearly with that of unlabeled lactate extraction (r = 0.86, P <
      0.0001), (11)CO(2) production correlated linearly with extraction of unlabeled
      lactate (r = 0.89, P < 0.0001, slope = 1.20 +/- 0.13). In studies with
      physiologic free fatty acids (FFA) (415 +/- 216 nmol/mL), (11)C-lactate was
      highly extracted (32% +/- 12%) and oxidized (26% +/- 14%), and PET
      monoexponential clearance and kinetic modeling analyses resulted in accurate
      estimates of lactate oxidation and metabolism. In contrast, supraphysiologic
      levels of plasma FFA (4,111 +/- 1,709 nmol/mL) led to poor PET estimates of
      lactate metabolism due to negligible lactate oxidation (1% +/- 2%) and complete
      backdiffusion of unmetabolized (11)C-lactate into the vasculature (28% +/- 22%).
      CONCLUSION: Under conditions of net lactate extraction, L-3-(11)C-lactate
      faithfully traces myocardial metabolism of exogenous lactate. Furthermore, in
      physiologic substrate environments, noninvasive measurements of lactate
      metabolism are feasible with PET using myocardial clearance analysis (oxidation)
      or compartmental modeling. Thus, L-3-(11)C-lactate should prove quite useful in
      widening our understanding of the role that lactate oxidation plays in the heart
      and other tissues and organs.

PMID- 18056335
TI  - L-type amino acid transporters LAT1 and LAT4 in cancer: uptake of 3-O-methyl-6
      18F-fluoro-L-dopa in human adenocarcinoma and squamous cell carcinoma in vitro
      and in vivo.
AB  - Expression of system L amino acid transporters (LAT) is strongly increased in
      many types of tumor cells. The purpose of this study was to demonstrate that
      (18)F-labeled amino acids, for example, 3-O-methyl-6-(18)F-fluoro-L-dopa ((18)F
      OMFD), that accumulate in tumors via LAT represent an important class of imaging
      agents for visualization of tumors in vivo by PET. METHODS: (18)F-OMFD uptake
      kinetics, transport inhibition, and system L messenger RNA expression were
      studied in vitro in human adenocarcinoma (HT-29), squamous cell carcinoma (FaDu),
      macrophages (THP-1), and primary aortic endothelial cells (HAEC) and in vivo in
      the corresponding mouse tumor xenograft models. RESULTS: Uptake of (18)F-OMFD in
      all cell lines tested was mediated mainly by the sodium-independent high-capacity
      LAT. We found higher uptake in FaDu cells (V(max), 10.6 +/- 1.1 nmol/min x mg of
      cell protein) and in the corresponding FaDu tumor xenografts than in the other
      cells and corresponding xenograft models studied. Quantitative messenger RNA
      analysis revealed that tumor cells and xenografts have a higher expression of
      LAT1 than do HAEC and THP-1 macrophages. However, only in the FaDu tumor model
      did an increased (18)F-OMFD uptake seem to be explained by increased LAT
      expression. Furthermore, we demonstrated a high expression of LAT4, a recently
      identified LAT. CONCLUSION: Our findings support the hypothesis that (18)F-OMFD
      is a tracer for visualization of tumor cells. (18)F-OMFD particularly seems to be
      a suitable tracer for diagnostic imaging of amino acid transport in poorly
      differentiated squamous cell head and neck carcinoma with increased LAT1 and LAT4
      expression.

PMID- 18056339
TI  - TLR ligands differentially modulate T cell responses to acute and chronic antigen
      presentation.
AB  - The outcome of peripheral T cell activation is thought to be largely determined
      by the context in which the cognate Ag is initially presented. In this framework,
      microbial products that can activate APCs via TLRs are considered critical in
      converting an otherwise tolerogenic context to an immunogenic one. We examine
      this idea using a model system where naive T cells are stimulated in the
      periphery by a persistent self Ag. The addition of multiple TLR ligands to this
      context, acutely or chronically, failed to significantly alter the tolerogenic
      phenotype in the responding T cells. This contrasts with the ability of such
      adjuvants to improve T cell responses to soluble peptide immunizations. We
      reconcile this difference by revealing a hitherto poorly appreciated property of
      TLR ligands, which extends the duration of soluble Ag presentation in vivo by an
      additional two to three days. Finally, we could replace the requirement for TLR
      mediated APC activation in soluble-Ag-induced T cell expansion and
      differentiation, by maintaining the Ag depot in vivo using repeated
      immunizations. These data suggest a novel process by which TLR ligands modulate T
      cell responses to acute Ags, without disrupting the induction of tolerance to
      persistent self Ags.

PMID- 18056338
TI  - COPs and POPs: modulators of inflammasome activity.
AB  - Inflammasomes represent molecular platforms for the activation of inflammatory
      caspases and are essential for processing and secretion of the inflammatory
      cytokines IL-1beta and IL-18. Multiple key proteins of inflammasomes contain
      caspase recruitment domains (CARDs) or pyrin domains (PYDs). Dissecting CARD- and
      PYD-mediated interactions substantially improved our understanding of the
      mechanisms by which these protein platforms are activated and emphasized their
      essential role during the inflammatory cytokine response. However, their precise
      regulation is still poorly understood. A family of small proteins that are
      composed of either a CARD or a PYD only emerged as important inflammasome
      regulators. These CARD-only proteins (COPs) and PYD-only proteins (POPs) function
      as endogenous dominant negative proteins that modulate the activity of
      inflammasomes in response to pathogen infection and tissue destruction. In this
      review we will summarize the most recent advances in the regulation of
      inflammasomes and highlight their importance for immunity and inflammatory
      disease.

PMID- 18056340
TI  - Inappropriate recruitment and activity by the Src homology region 2 domain
      containing phosphatase 1 (SHP1) is responsible for receptor dominance in the SHIP
      deficient NK cell.
AB  - We have previously demonstrated that the NKR repertoire is profoundly disrupted
      by SHIP deficiency. This repertoire disruption is characterized by receptor
      dominance where inhibitory signals from 2B4 repress killing of complex targets
      expressing MHC class I and activating ligands. In this study, we examine the
      molecular basis of receptor dominance in SHIP-/- NK cells. In this study, we show
      that in SHIP-/- NK cells there is a pronounced bias toward the 2B4 long isoform.
      We have also characterized signaling molecules recruited to 2B4 in SHIP-/- NK
      cells. Interestingly, we find that approximately 10- to 16-fold more Src homology
      region 2 domain-containing phosphatase 1 (SHP1) is recruited to 2B4 in SHIP-/- NK
      cells when compared with wild type. Consistent with SHP1 overrecruitment,
      treatment with sodium orthovanadate or a novel inhibitor with micromolar activity
      against SHP1 restores the ability of SHIP-/- NK cells to kill Rae1+ RMA and M157+
      targets. These findings define the molecular basis for hyporesponsiveness by SHIP
      deficient NK cells.

PMID- 18056341
TI  - Altered distribution of H60 minor H antigen-specific CD8 T cells and attenuated
      chronic vasculopathy in minor histocompatibility antigen mismatched heart
      transplantation in Cxcr3-/- mouse recipients.
AB  - Chemokine-chemokine receptor interactions and the subsequent recruitment of T
      lymphocytes to the graft are believed to be among the initial events in the
      development of acute and chronic rejection of heart transplants. We sought to
      determine the role of chemokine receptor Cxcr3 on the development of acute and
      chronic rejection in a multiple minor Ag mismatched mouse heart transplant model.
      The frequencies and kinetics of immunodominant H60 (LTFNYRNL) miHA-specific CD8 T
      cells in wild-type or Cxcr3-/- C57BL/6 recipients were monitored using MHC class
      I tetramer after BALB/b donor hearts were transplanted. Acceptance of grafts,
      severity of rejection, and infiltration of T cells were not altered in Cxcr3-/-
      recipients. However, graft survival was moderately prolonged in Cxcr3-/-
      recipient mice undergoing acute rejection. Analyses of splenocytes, PBLs, and
      graft-infiltrating cells revealed increased alloreactive T cells (H60-specific
      CD8 T cells) in the peripheral blood and spleen but not in the graft. Adoptively
      transferred Cxcr3-/- CD8 T cells in the BALB/b heart-bearing B6 scid mice showed
      retention of alloreactive CD8 T cells in the blood but less infiltration into the
      graft. Cxcr3-/- recipients with long-term graft survival also showed a marked
      decrease of CD8+ T cell infiltration and reduced neo-intimal hyperplasia. These
      data indicate that Cxcr3 plays a critical role in the trafficking as well as
      activation of alloreactive T cells. This role is most eminent in a transplant
      model when a less complex inflammatory milieu is involved such as a well-matched
      graft and chronic rejection.

PMID- 18056342
TI  - Inverse Rap1 and phospho-ERK expression discriminate the maintenance phase of
      tolerance and priming of antigen-specific CD4+ T cells in vitro and in vivo.
AB  - T cell recognition of Ag can result in priming or tolerance depending on the
      context in which Ag is recognized. Previously, we have reported that these
      distinct functional outcomes are associated with marked differences in the
      amplitude, kinetics, and cellular localization of activated, pERK signals at the
      level of individual Ag-specific T cells in vitro. Here, we show that the GTPase
      Rap1, which can antagonize the generation of such pERK signals and has been
      reported to accumulate in tolerant cells, exhibits an inverse pattern of
      expression to pERK in individual Ag-specific primed and tolerized T cells.
      Although pERK is expressed by more primed than tolerized T cells when
      rechallenged with Ag in vitro, Rap1 is expressed by higher percentages of
      tolerant compared with primed Ag-specific T cells. Moreover, whereas pERK
      localizes to the TCR and lipid rafts in primed cells, but exhibits a diffuse
      cellular distribution in tolerized cells, Rap1 colocalizes with the TCR and lipid
      raft structures under conditions of tolerance, but not priming, in vitro. This
      inverse relationship between Rap1 and pERK expression is physiologically
      relevant, given that we observed the same patterns in Ag-specific T cells in
      situ, following induction of priming and tolerance in vivo. Together, these data
      suggest that the maintenance of tolerance of individual Ag-specific T cells may
      reflect the recruitment of up-regulated Rap1 to the immune synapse, potentially
      resulting in sequestration of Raf-1 and uncoupling of the TCR from the Ras-ERK
      MAPK cascade.

PMID- 18056343
TI  - A novel role of IL-2 in organ-specific autoimmune inflammation beyond regulatory
      T cell checkpoint: both IL-2 knockout and Fas mutation prolong lifespan of Scurfy
      mice but by different mechanisms.
AB  - Mutation of the Foxp3 transcription factor in Scurfy (Sf) mice results in
      complete absence of the CD4+Foxp3+ regulatory T cells (Tregs), severe multiorgan
      autoimmune syndrome, and early death at 4 wk of age. However, Sf mice
      simultaneously bearing the Il2-/- (Sf.Il2-/-) or Faslpr/lpr gene (Sf.Faslpr/lpr)
      have extended lifespan despite totally lacking Tregs, indicating a role of IL-2
      and CD95 (Fas) signaling pathways in the multiorgan autoimmune syndrome beyond
      the Treg checkpoint. IL-2 has been implicated in regulating lymphoproliferation
      and CD178 (FasL) expression. However, Sf.Il2-/- mice have increased
      lymphoproliferation and FasL expression. Importantly, the pattern of organ
      specific autoimmune response of Sf.Il2-/-mice resembled IL-2 knockout mice
      whereas that of Sf.Faslpr/lpr was similar to Sf mice, indicating that the
      distinct and weakened autoimmune manifestation in IL-2 knockout mice was not
      caused by the residual Tregs. Our study demonstrated a novel role of IL-2 in
      regulating multiorgan autoimmune inflammation beyond the Treg checkpoint and
      indicated that both Il2-/- and Faslpr/lpr genes prolong the lifespan of Sf mice
      but by different mechanisms.

PMID- 18056344
TI  - Passive immunization against the MHC class I molecule Mamu-AG disrupts rhesus
      placental development and endometrial responses.
AB  - The unique MHC phenotype of the human and nonhuman primate placenta has suggested
      a potential role in maternal-fetal immune tolerance, pregnancy success, and
      maternal as well as fetal well-being. In the rhesus monkey (Macaca mulatta) a
      nonclassical MHC class I molecule, Mamu-AG, is a putative homologue of HLA-G and
      is hypothesized to play a role in maternal-fetal immune interactions during
      pregnancy. Rhesus monkeys were passively immunized during the second week after
      implantation with a mAb against Mamu-AG. Passive immunization altered the growth
      and vascularization of the fetal placenta, the placental modification of maternal
      endometrial vessels, the maternal leukocyte response to implantation, and the
      differentiation of epithelial and stromal cells in the endometrium. These data
      are the first to demonstrate in vivo the importance of MHC class I molecules
      expressed on primate trophoblasts in establishing an important environment for
      pregnancy success through coordinated interactions between endometrial and fetal
      tissues.

PMID- 18056345
TI  - Receptor for advanced glycation end products expression on T cells contributes to
      antigen-specific cellular expansion in vivo.
AB  - Receptor for advanced glycation end products (RAGE) is an activation receptor
      triggered by inflammatory S100/calgranulins and high mobility group box-1
      ligands. We have investigated the importance of RAGE on Ag priming of T cells in
      murine models in vivo. RAGE is inducibly up-regulated during T cell activation.
      Transfer of RAGE-deficient OT II T cells into OVA-immunized hosts resulted in
      reduced proliferative responses that were further diminished in RAGE-deficient
      recipients. Examination of RAGE-deficient dendritic cells did not reveal
      functional impairment in Ag presentation, maturation, or migratory capacities.
      However, RAGE-deficient T cells showed markedly impaired proliferative responses
      in vitro to nominal and alloantigens, in parallel with decreased production of
      IFN-gamma and IL-2. These data indicate that RAGE expressed on T cells is
      required for efficient priming of T cells and elucidate critical roles for RAGE
      engagement during cognate dendritic cell-T cell interactions.

PMID- 18056346
TI  - Chronic antigen stimulation in vivo induces a distinct population of antigen
      specific Foxp3 CD25 regulatory T cells.
AB  - The concept of immune regulation/suppression has been well-established and,
      besides thymus-derived CD4+CD25+ regulatory T (TR) cells, it became clear that a
      variety of additional peripherally induced TR cells play vital roles in
      protection from many harmful immune responses including intestinal inflammation.
      In the present study, we have analyzed in vivo-induced Ag-specific CD4+ TR cells
      with respect to their molecular and functional phenotype. By comparative genomics
      we could show that these Ag-specific TR cells induced by chronic Ag stimulation
      in vivo clearly differ in their genetic program from naturally occurring thymus
      derived CD4+CD25+ TR cells. This distinct population of induced TR cells express
      neither CD25 nor the TR-associated transcription factor Foxp3. Strikingly, CD25
      is not even up-regulated upon stimulation. Despite the lack in Foxp3 expression,
      these in vivo-induced CD25- TR cells are able to interfere with an Ag-specific
      CD8+ T cell-mediated intestinal inflammation without significant increase in CD25
      and Foxp3 expression. Thus, our results demonstrate that in vivo-induced Ag
      specific TR cells represent a distinct population of Foxp3-CD25- TR cells with
      regulatory capacity both in vitro and in vivo.

PMID- 18056347
TI  - Lymphotoxin beta receptor is required for the migration and selection of
      autoreactive T cells in thymic medulla.
AB  - How organ-specific central tolerance is established and regulated has been an
      intriguing question. Lymphotoxin beta receptor (LTbetaR) deficiency is associated
      with autoimmune phenotypes characterized by humoral and cellular autoreactivity
      to peripheral organs. Whether this results from defective negative selection of T
      cells directed at tissue-restricted Ags has not been well understood. By tracing
      the development of OT-I thymocytes in rat insulin 2 promoter-mOVA transgenic mice
      on either Ltbr+/+ or Ltbr-/- background, we demonstrate that LTbetaR is necessary
      for thymic negative selection. LTbetaR deficiency resulted in a dramatic escape
      of "neo-self" specific OT-I cells that persist in circulation and lead to
      development of peri-insulitis. When the underlying mechanism was further
      explored, we found interestingly that LTbetaR deficiency did not result in
      reduced thymic expression of mOVA. Instead, LTbetaR was revealed to control the
      expression of thymic medullary chemokines (secondary lymphoid tissue chemokine
      (SLC) and EBV-induced molecule 1 ligand chemokine (ELC)) which are required for
      thymocytes migration and selection in medulla. Furthermore, RIP-mOVA transgenic
      mice on SLC/ELC deficient background (plt) demonstrated significant impaired
      negative selection of OT-I cells, suggesting that the dysregulation of SLC/ELC-
      expression alone in Ltbr-/- thymi can be sufficient to impair thymic negative
      selection. Thus, LTbetaR has been revealed to play an important role in thymic
      negative selection of organ-specific thymocytes through thymic medullary
      chemokines regulation.

PMID- 18056348
TI  - CD28 deficiency exacerbates joint inflammation upon Borrelia burgdorferi
      infection, resulting in the development of chronic Lyme arthritis.
AB  - Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi (Bb), is a
      multisystem illness, affecting many organs, such as the heart, the nervous
      system, and the joints. Months after Bb infection, approximately 60% of patients
      experience intermittent arthritic attacks, a condition that in some individuals
      progresses to chronic joint inflammation. Although mice develop acute arthritis
      in response to Bb infection, the joint inflammation clears after 2 wk, despite
      continuous infection, only very rarely presenting with chronic Lyme arthritis.
      Thus, the lack of an animal system has so far prevented the elucidation of this
      persistent inflammatory process that occurs in humans. In this study, we report
      that the majority of Bb-infected CD28-/- mice develop chronic Lyme arthritis.
      Consistent with observations in chronic Lyme arthritis patients, the infected
      mutant, but not wild-type mice present recurring monoarticular arthritis over an
      extended time period, as well as anti-outer surface protein A of Bb serum titers.
      Furthermore, we demonstrate that anti-outer surface protein A Abs develop in
      these mice only after establishment of chronic Lyme arthritis. Thus, the Bb
      infected CD28-/- mice provide a murine model for studying chronic Lyme arthritis.

PMID- 18056349
TI  - Enhancement of NF-kappaB activation in lymphocytes prevents T cell apoptosis and
      improves survival in murine sepsis.
AB  - Sepsis induces extensive lymphocyte apoptosis that contributes to
      immunosuppression and mortality. Activation of the canonical NF-kappaB pathway,
      however, prevents TNF-alpha-induced lymphocyte apoptosis. In this study the
      function of canonical NF-kappaB in T cells was studied in the context of murine
      sepsis. Upon cecal ligation and puncture (CLP), NF-kappaB DNA binding activity in
      thymocytes declines relative to sham-operated mice. This decline in NF-kappaB
      activity is most likely due to posttranslational modifications such as
      deacetylation of p65. In parallel, cleavage of procaspase-3 is increased, whereas
      expression of NF-kappaB-dependent antiapoptotic genes Bcl-xL and c-IAP2 is
      suppressed upon sepsis induction. Interestingly, adoptive transfer of
      IkappaBalpha-deficient fetal liver stem cells into sublethally irradiated
      lymphopenic host mice reduced the decline in thymocyte survival, increased
      peripheral T cell numbers, and improved the mortality rate relative to wild-type
      reconstituted hosts after cecal ligation and puncture. In conclusion, lymphocyte
      directed augmentation of canonical NF-kappaB ameliorates immunosuppression during
      murine sepsis. These data provide evidence for a new approach in sepsis therapy.

PMID- 18056350
TI  - Selective inhibition of inducible NO synthase activity in vivo reverses
      inflammatory abnormalities in surfactant protein D-deficient mice.
AB  - Surfactant protein D (SP-D)-deficient (SP-D-/-) mice exhibit early development of
      emphysema. Previously we have shown that SP-D deficiency results in increased
      production and activity of inducible NO synthase (iNOS). In this study, we
      examined whether treatment with the iNOS inhibitor 1400W could inhibit the
      inflammatory phenotype. Mice were treated with 1400W systemically for 7 wk from 3
      wk of age. Treatment reduced total lung NO synthase activity to 14.7+/-6.1% of
      saline-treated 10-wk-old SP-D-/- littermates. Long-term administration of 1400W
      reduced lung inflammation and cellular infiltration; and significantly attenuated
      the increased levels of matrix metalloproteinases 2 and 9, chemokines (KC, TARC),
      and cytokines (IFN-gamma) seen in bronchoalveolar lavage (BAL) of SP-D-/- mice.
      Abrogation of these levels was associated with decreasing BAL chemotactic
      activity for RAW cells. Two weeks of treatment with 1400W reduced total lung NO
      synthase (NOS) activity to 12.7+/-6.3% of saline-treated SP-D-/- mice. Short-term
      iNOS inhibition resulted in attenuation of pulmonary inflammation within SP-D-/-
      mice as shown by decreases in total BAL cell count (63+/-6% of SP-D-/- control),
      macrophage size (>25 microm) within the BAL (62+/-10% of SP-D-/- control), and a
      percentage of BAL macrophages producing oxidants (76+/-9% of SP-D-/- control).
      These studies showed that s.c. delivery of 1400W can be achieved in vivo and can
      attenuate the inflammatory processes within SP-D deficiency. Our results
      represent the first report linking defects in the innate immune system in the
      lung with alterations in NO homeostasis.

PMID- 18056351
TI  - IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required
      for the development of autoimmune encephalomyelitis.
AB  - Lately, IL-17-secreting Th cells have received an overwhelming amount of
      attention and are now widely held to be the major pathogenic population in
      autoimmune diseases. In particular, IL-22-secreting Th17 cells were shown to
      specifically mark the highly pathogenic population of self-reactive T cells in
      experimental autoimmune encephalomyelitis (EAE). As IL-17A itself was found to
      only play a minor role during the development of EAE, IL-22 is now postulated to
      contribute to the pathogenic function of Th17 cells. The goal of this study was
      to determine the role and function of IL-22 during the development of CNS
      autoimmunity in vivo. We found that CNS-invading encephalitogenic Th17 cells
      coexpress IL-22 and that IL-22 is specifically induced by IL-23 in autoimmune
      pathogenic CD4+ T cells in a time- and dose-dependent manner. We next generated
      IL-22-/- mice, which--in contrast to the prediction that expression of
      inflammatory cytokines by CNS-invading T cells inevitably confers pathogenic
      function--turned out to be fully susceptible to EAE. Taken together, we show that
      self-reactive Th cells coexpress IL-17 and IL-22, but that the latter also does
      not appear to be directly involved in autoimmune pathogenesis of the CNS.

PMID- 18056352
TI  - Transduction of phosphatase and tensin homolog deleted on chromosome 10 into
      eosinophils attenuates survival, chemotaxis, and airway inflammation.
AB  - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is part of a
      complex signaling system that affects a variety of important cell functions. PTEN
      antagonizes the action of PI3K by dephosphorylating the signaling lipid
      phosphatidylinositol 3,4,5-triphosphate. In the present study, we used a TAT
      fusion protein transduction system to elucidate the role of PTEN in eosinophils
      and airway inflammation. A small region of the HIV TAT protein (YGRKKRRQRRR), a
      protein transduction domain known to enter mammalian cells efficiently, was fused
      to the N terminus of PTEN. Flow cytometric analysis of annexin V- and propidium
      iodide-stained cells was used to assess eosinophil survival. A chemotaxis assay
      was performed using a Boyden chamber. Cell analysis in bronchoalveolar lavage
      fluid and histological examinations were performed using OVA-challenged A/J mice.
      We found that TAT-PTEN was successfully internalized into eosinophils and
      functioned as a phosphatase in situ. TAT-PTEN, but not a TAT-GFP control protein,
      blocked the ability of IL-5 to prevent the apoptosis of eosinophils from allergic
      subjects. The eotaxin-induced eosinophil chemotaxis was inhibited by TAT-PTEN in
      a dose-dependent manner. Intranasal pretreatment with TAT-PTEN, but not TAT-GFP,
      significantly inhibited the OVA-induced eosinophil infiltration in
      bronchoalveolar lavage fluid. Histological examination of the lung, including H&E
      and Alcian blue/periodic acid-Schiff staining, revealed that TAT-PTEN, but not
      TAT-GFP, abrogated eosinophilic inflammation and mucus production. Our results
      suggest that PTEN negatively regulates eosinophil survival, chemotaxis, and
      allergic inflammation. The pharmacological targeting of PTEN may constitute a new
      strategy for the treatment of eosinophilic disorders.

PMID- 18056353
TI  - Formyl peptide receptor-1 activation enhances intestinal epithelial cell
      restitution through phosphatidylinositol 3-kinase-dependent activation of Rac1
      and Cdc42.
AB  - Inflammatory disorders of the gastrointestinal tract result in the breakdown of
      the intestinal epithelial barrier in the form of erosion and ulceration. To
      reestablish the epithelial barrier, the epithelium must efficiently migrate to
      reseal wounds. Numerous signaling cascades are involved in the induction and
      regulation of this complex process. N-formyl peptide receptors comprise a group
      of Gi-coupled receptors that regulate innate immune responses. Previously, we
      identified the expression of functional N-formyl peptide receptors in model SK
      CO15 intestinal epithelial cells and observed a role for activation of these
      receptors in regulating cellular invasive behavior. In these studies, we
      performed formyl peptide receptor-1 (FPR) localization and evaluated its role in
      regulating intestinal epithelial cell wound closure. Immunolocalization studies
      using a recently developed specific monoclonal anti-FPR Ab demonstrated its
      localization along the lateral membrane of crypt epithelial cells in normal human
      colonic epithelium. In vitro studies using the classical FPR agonist fMLF showed
      that FPR activation significantly enhances model intestinal epithelial cell
      restitution and that FPR localized along actin filaments in lamellipodial and
      filopodial extrusions. The increase in cell migration was associated with
      activation of PI3K, Rac1, and Cdc42. Pharmacologic inhibition of PI3K activity
      abrogated the fMLF-induced increase in wound closure and activation of both Rac1
      and Cdc42. Inhibition of Rac1 and Cdc42 using pharmacologic inhibitors and
      dominant negative mutants also inhibited the fMLF-induced increase in cell
      migration. Taken together, theses results support a novel role for FPR
      stimulation in enhancing intestinal epithelial cell restitution through PI3K
      dependent activation of Rac1 and Cdc42.

PMID- 18056354
TI  - Systemic and mucosal infection program protective memory CD8 T cells in the
      vaginal mucosa.
AB  - Whether mucosal immunization is required for optimal protective CD8 T cell memory
      at mucosal surfaces is controversial. In this study, using an adoptive transfer
      system, we compare the efficacy of two routes of acute lymphocytic
      choriomeningitis viral infection on the generation, maintenance, and localization
      of Ag-specific CD8 T cells in tissues, including the vaginal mucosa.
      Surprisingly, at day 8, i.p. infection results in higher numbers of Ag-specific
      CD8 T cells in the vaginal mucosa and iliac lymph node, as well as 2-3x more Ag
      specific CD8 T cells that coexpress both IFN-gamma and TNF-alpha in comparison to
      the intranasal route of infection. Expression of the integrin/activation marker
      CD103 (alphaEbeta7) is low on vaginal mucosal Ag-specific CD8 T cells in
      comparison to gut mucosal intraepithelial lymphocytes. At memory, no differences
      are evident in the number, cytokine production, or protective function of Ag
      specific CD8 T cells in the vaginal mucosa comparing the two routes of infection.
      However, differences persist in the cytokine profile of genital tract vs
      peripheral Ag-specific CD8 T cells. So although the initial route of infection,
      as well as tissue microenvironment, appear to influence both the magnitude and
      quality of the effector CD8 T cell response, both systemic and mucosal infection
      are equally effective in the differentiation of protective memory CD8 T cell
      responses against vaginal pathogenic challenge.

PMID- 18056356
TI  - Analysis of direct and cross-presentation of antigens in TPPII knockout mice.
AB  - Tripeptidyl peptidase II (TPPII) is an oligopeptidase forming giant complexes in
      the cytosol that have high exo-, but also, endoproteolytic activity.
      Immunohistochemically, the complexes appear as distinct foci in the cytosol. In
      part controversial biochemical and functional studies have suggested that TPPII
      contributes, on the one hand, positively to Ag processing by generating epitope
      carboxyl termini or by trimming epitope precursors, and, on the other, negatively
      by destroying potentially antigenic peptides. To clarify which of these roles is
      predominant, we generated and analyzed TPPII-deficient mice. Cell surface levels
      of MHC class I peptide complexes tended to be increased on most cell types of
      these mice. Although presentation of three individual epitopes derived from
      lymphocytic choriomeningitis virus was not elevated on TPPII-/- cells, that of
      the immunodominant OVA epitope SIINFEKL was significantly enhanced. Consistent
      with this, degradation of a synthetic peptide corresponding to the OVA epitope
      and of another corresponding to a precursor thereof, both being proteasomally
      generated OVA fragments, was delayed in TPPII-deficient cytosolic extracts. In
      addition, dendritic cell cross-presentation of phagocytosed OVA and of OVA
      internalized as an immune complex was increased to about the same level as direct
      presentation of the Ag. The data suggest a moderate, predominantly destructive
      role of TPPII in class I Ag processing, in line with our finding that TPPII is
      not induced by IFN-gamma, which up-regulates numerous, predominantly constructive
      components of the Ag processing and presentation machinery.

PMID- 18056357
TI  - Pregnancy suppresses experimental autoimmune encephalomyelitis through
      immunoregulatory cytokine production.
AB  - Women with multiple sclerosis (MS) often experience a decrease in relapse rate
      during pregnancy, most notably during the third trimester, with a flare of
      disease activity 3-6 mo postpartum. Studies in experimental autoimmune
      encephalomyelitis (EAE), an animal model for MS, have shown that pregnancy delays
      the onset and decreases the incidence of disease. We investigated the effect of
      pregnancy and the postpartum period in a remitting-relapsing model of murine EAE.
      When immunization occurs during pregnancy, mice show a reduction in the incidence
      of EAE as well as a decrease in clinical severity, while mice immunized during
      the postpartum period exhibit more severe disease. No differences in lymphocyte
      proliferation or expression of activation markers were noted when immunization
      occurred during pregnancy as compared with the nonpregnant controls. Mice
      immunized during pregnancy produced less TNF-alpha and IL-17, and showed an
      increased number of IL-10-secreting cells within the CD11b+, CD11c+, CD19+, and
      CD4+/CD25+ populations. No differences were noted in the production of IFN-gamma,
      IL-2, IL-4, and IL-5. These results suggest that when an Ag is introduced during
      pregnancy, an immunoregulatory rather than an immunosuppressive or Th2
      environment predominates.

PMID- 18056355
TI  - LILRA2 activation inhibits dendritic cell differentiation and antigen
      presentation to T cells.
AB  - The differentiation of monocytes into dendritic cells (DC) is a key mechanism by
      which the innate immune system instructs the adaptive T cell response. In this
      study, we investigated whether leukocyte Ig-like receptor A2 (LILRA2) regulates
      DC differentiation by using leprosy as a model. LILRA2 protein expression was
      increased in the lesions of the progressive, lepromatous form vs the self
      limited, tuberculoid form of leprosy. Double immunolabeling revealed LILRA2
      expression on CD14+, CD68+ monocytes/macrophages. Activation of LILRA2 on
      peripheral blood monocytes impaired GM-CSF induced differentiation into immature
      DC, as evidenced by reduced expression of DC markers (MHC class II, CD1b, CD40,
      and CD206), but not macrophage markers (CD209 and CD14). Furthermore, LILRA2
      activation abrogated Ag presentation to both CD1b- and MHC class II-restricted,
      Mycobacterium leprae-reactive T cells derived from leprosy patients, while
      cytokine profiles of LILRA2-activated monocytes demonstrated an increase in TNF
      alpha, IL-6, IL-8, IL-12, and IL-10, but little effect on TGF-beta. Therefore,
      LILRA2 activation, by altering GM-CSF-induced monocyte differentiation into
      immature DC, provides a mechanism for down-regulating the ability of the innate
      immune system to activate the adaptive T cell response while promoting an
      inflammatory response.

PMID- 18056358
TI  - Atypical memory phenotype T cells with low homeostatic potential and impaired TCR
      signaling and regulatory T cell function in Foxn1Delta/Delta mutant mice.
AB  - Foxn1Delta/Delta mutants have a block in thymic epithelial cell differentiation
      at an intermediate progenitor stage, resulting in reduced thymocyte cellularity
      and blocks at the double-negative and double-positive stages. Whereas naive
      single-positive thymocytes were reduced >500-fold in the adult Foxn1Delta/Delta
      thymus, peripheral T cell numbers were reduced only 10-fold. The current data
      shows that Foxn1Delta/Delta peripheral T cells had increased expression of
      activation markers and the ability to produce IL-2 and IFN-gamma. These cells
      acquired this profile immediately after leaving the thymus as early as the
      newborn stage and maintained high steady-state proliferation in vivo but
      decreased proliferation in response to TCR stimulation in vitro. Single-positive
      thymocytes and naive T cells also had constitutively low alphabetaTCR and IL7R
      expression. These cells also displayed reduced ability to undergo homeostatic
      proliferation and increased rates of apoptosis. Although the frequency of
      Foxp3+CD4+CD25+ T cells was normal in Foxn1Delta/Delta mutant mice, these cells
      failed to have suppressor function, resulting in reduced regulatory T cell
      activity. Recent data from our laboratory suggest that T cells in the
      Foxn1Delta/Delta thymus develop from atypical progenitor cells via a noncanonical
      pathway. Our results suggest that the phenotype of peripheral T cells in
      Foxn1Delta/Delta mutant mice is the result of atypical progenitor cells
      developing in an abnormal thymic microenvironment with a deficient TCR and IL7
      signaling system.

PMID- 18056359
TI  - Anti-CD28 antibodies modify regulatory mechanisms and reinforce tolerance in
      CD40Ig-treated heart allograft recipients.
AB  - Blockade of CD40-CD40 ligand (CD40L) costimulation has been shown to synergize
      with that of CTLA4/CD28-B7 to promote transplant tolerance. To date, however,
      CD28-B7 interactions have been prevented using B7-blocking reagents like CTLA4-Ig
      that inhibit CD28-B7 together with CTLA4-B7 interactions. In this study, we have
      tested anti-CD28 Abs to prevent selectively CD28-B7 interactions while preserving
      CTLA4-B7 in addition to CD40-CD40L blockade. In the LEW.1W to LEW.1A rat
      combination, interfering with CD40-CD40L interactions by CD40Ig administration
      through gene transfer resulted in indefinite heart allograft survival due to the
      appearance of clonotypic CD8+CD45RClow regulatory T cells that were capable of
      transferring the tolerant state to naive animals. However, cardiac transplants in
      these recipients systematically developed chronic rejection lesions. Whereas anti
      CD28 Ab monotherapy only delayed acute rejection and failed to induce tolerance,
      coadministration of anti-CD28 Abs and CD40Ig resulted in the long-term
      acceptation of allografts without chronic rejection lesions in 60% of the
      recipients, reduced the level of intragraft mRNA transcripts for cytokines and
      immune factors, and fully abrogated alloantibody production. In addition, the
      nature of regulatory cells was modified: the CD8+CD45RClow clonotypic T cells
      described in the CD40Ig-treated animals could not be found in cotreated animals,
      and the other CD8+CD45RClow cells had no regulatory activity and a different
      cytokine expression profile. Instead, in cotreated recipients we found IDO
      dependent non-T cells with regulatory activity in vitro. Thus, the addition of a
      short-term anti-CD28 treatment with CD40Ig resulted in decreased heart allograft
      chronic rejection lesions, complete inhibition of Ab production, and modified
      regulatory mechanisms.

PMID- 18056360
TI  - Critical role for CXC chemokine ligand 16 (SR-PSOX) in Th1 response mediated by
      NKT cells.
AB  - The transmembrane chemokine CXCL 16 (CXCL16), which is the same molecule as the
      scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR
      PSOX), has been shown to mediate chemotaxis and adhesion of CXC chemokine
      receptor 6-expressing cells such as NKT and activated Th1 cells. We generated SR
      PSOX/CXCL16-deficient mice and examined the role of this chemokine in vivo. The
      mutant mice showed a reduced number of liver NKT cells, and decreased production
      of IFN-gamma and IL-4 by administration of alpha-galactosylceramide
      (alphaGalCer). Of note, the alphaGalCer-induced production of IFN-gamma was more
      severely impaired than the production of IL-4 in SR-PSOX-deficient mice. In this
      context, SR-PSOX-deficient mice showed impaired sensitivity to alphaGalCer
      induced anti-tumor effect mediated by IFN-gamma from NKT cells. NKT cells from
      wild-type mice showed impaired production of IFN-gamma, but not IL-4, after their
      culture with alphaGalCer and APCs from mutant mice. Moreover, Propionibacterium
      acnes-induced in vivo Th1 responses were severely impaired in SR-PSOX-deficient
      as well as NKT KO mice. Taken together, SR-PSOX/CXCL16 plays an important role in
      not only the production of IFN-gamma by NKT cells, but also promotion of Th1
      inclined immune responses mediated by NKT cells.

PMID- 18056361
TI  - Cytokine-mediated regulation of human B cell differentiation into Ig-secreting
      cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells.
AB  - Differentiation of B cells into Ig-secreting cells (ISC) is critical for the
      generation of protective humoral immune responses. Because of the important role
      played by secreted Ig in host protection against infection, it is necessary to
      identify molecules that control B cell differentiation. Recently, IL-21 was
      reported to generate ISC from activated human B cells. In this study, we examined
      the effects of IL-21 on the differentiation of all human mature B cell subsets-
      neonatal, transitional, naive, germinal center, IgM-memory, and isotype-switched
      memory cells--into ISC and compared its efficacy to that of IL-10, a well-known
      mediator of human B cell differentiation. IL-21 rapidly induced the generation of
      ISC and the secretion of vast quantities IgM, IgG and IgA from all of these B
      cell subsets. Its effect exceeded that of IL-10 by up to 100-fold, highlighting
      the potency of IL-21 as a B cell differentiation factor. Strikingly, IL-4
      suppressed the stimulatory effects of IL-21 on naive B cells by reducing the
      expression of B-lymphocyte induced maturation protein-1 (Blimp-1). In contrast,
      memory B cells were resistant to the inhibitory effects of IL-4. Finally, the
      ability of human tonsillar CD4+CXCR5+CCR7- T follicular helper (TFH) cells, known
      to be a rich source of IL-21, to induce the differentiation of autologous B cells
      into ISC was mediated by the production of IL-21. These findings suggest that IL
      21 produced by TFH cells during the primary as well as the subsequent responses
      to T cell-dependent Ag makes a major contribution to eliciting and maintaining
      long-lived humoral immunity.

PMID- 18056362
TI  - Hyaluronan synthesis is required for IL-2-mediated T cell proliferation.
AB  - Hyaluronan (HA) is a glycosaminoglycan composed of N-acetylglucosamine and
      glucuronic acid subunits. Previous studies have suggested that CD44 expressed by
      T cells bind exogenous HA for their proliferation. However, HA endogenously
      synthesized by T cells may participate in their autocrine proliferation. In this
      study, we examined the role of endogenous HA in T cell proliferation using the
      highly specific HA synthase inhibitor, 4-methylumbelliferone (4-MU). We found
      that 4-MU inhibited the mitogen-induced synthesis of HA by T cells. Moreover, 4
      MU inhibited T cell proliferation in a dose-dependent manner when cells were
      cultured with different stimuli, including Con A, PMA/ionomycin, and allogeneic
      spleen cells. Furthermore, 4-MU inhibited mitogen-stimulated IL-2 secretion,
      suggesting that HA may play a role in the production of this cytokine. Addition
      of IL-2 to T cells treated with 4-MU and Con A reversed the block in cell
      proliferation, showing that impaired IL-2 production is a likely mechanism for
      the inhibited division of T cells. Surprisingly, an anti-CD44 Ab antagonistic for
      HA binding did not reduce IL-2 secretion or T cell proliferation. Importantly, 4
      MU did not alter the surface expression of CD44 or the ability of CD44 to bind to
      HA. Thus, HA-mediated IL-2 production and T cell proliferation are CD44
      independent. Our results strongly suggest that HA synthesized by T cells
      themselves is critical for their IL-2-mediated proliferation and have revealed a
      previously unrecognized role for endogenous HA in T cell biology.

PMID- 18056363
TI  - Leishmania mexicana infection induces impaired lymph node expansion and Th1 cell
      differentiation despite normal T cell proliferation.
AB  - Leishmania mexicana infections in C57BL/6 mice are associated with minimal immune
      responses and persistent cutaneous lesions. In contrast, Leishmania major elicits
      a robust Th1 response that promotes lesion resolution. We investigated whether
      the nonhealing phenotype associated with L. mexicana was due to a failure of L.
      mexicana to activate T cells. In vivo T cell responses to infection were assessed
      by tracking the behavior of labeled naive T cells following the transfer of these
      cells into congenic mice. Although L. mexicana infection was associated with
      minimal expansion of the draining lymph nodes, we observed no difference in the
      percentage of T cells proliferating in response to L. mexicana and L. major.
      Instead, differences in the size and cellularity of lymph nodes were associated
      with decreased recruitment of cells trafficking to the lymph node. Furthermore,
      we found that T cells responding to L. mexicana infection were less able to
      differentiate into IFN-gamma producing cells, and this deficit extended to
      previously activated T cells as well. Coadministration of CpG-containing
      oligodeoxynucleotides at the time of infection overcame this deficit and promoted
      disease resolution. Taken together, our results identify two distinct components
      that contribute to the minimal immune response associated with L. mexicana
      infection. First, despite ample levels of T cell proliferation, L. mexicana fails
      to induce substantial lymph node expansion, which limits the number of responding
      T cells. Second, L. mexicana infection fails to drive the differentiation of the
      majority of responding cells into IFN-gamma producers.

PMID- 18056364
TI  - Introduction of zwitterionic motifs into bacterial polysaccharides generates TLR2
      agonists able to activate APCs.
AB  - It was shown previously that bacterial polysaccharides (PS), which naturally
      contain both positive and negative charges, are able to activate T cells and
      APCs. However, the vast majority of bacterial PS are anionic and do not have
      these properties. In this study, we show that chemical introduction of positive
      charges into naturally anionic bacterial PS confers to the resulting zwitterionic
      PS (ZPS) the ability to activate pure human monocytes, monocyte-derived dendritic
      cells, and mouse bone marrow-derived dendritic cells, as do natural bacterial
      ZPS. Cells are induced to up-regulate MHC class II and costimulatory molecules
      and to produce cytokines. In mixed monocyte-T cell cocultures, ZPS induce MHC II
      dependent T cell proliferation and up-regulation of activation markers. These
      stimulatory qualities of ZPS disappear when the positive charge is chemically
      removed from the molecules and thus the zwitterionic motif is destroyed. The
      ability of natural and chemically derived ZPS to activate APCs can be blocked by
      anti-TLR2 mAbs, and TLR2 transfectants show reporter gene transcription upon
      incubation with ZPS. In conclusion, the generation of a zwitterionic motif in
      bacterial PS confers the ability to activate both APCs and T cells. This finding
      has important implications for the design of novel polysaccharide vaccines.

PMID- 18056365
TI  - Dendritic cell maturation results in pronounced changes in glycan expression
      affecting recognition by siglecs and galectins.
AB  - Dendritic cells (DC) are the most potent APC in the organism. Immature dendritic
      cells (iDC) reside in the tissue where they capture pathogens whereas mature
      dendritic cells (mDC) are able to activate T cells in the lymph node. This
      dramatic functional change is mediated by an important genetic reprogramming.
      Glycosylation is the most common form of posttranslational modification of
      proteins and has been implicated in multiple aspects of the immune response. To
      investigate the involvement of glycosylation in the changes that occur during DC
      maturation, we have studied the differences in the glycan profile of iDC and mDC
      as well as their glycosylation machinery. For information relating to glycan
      biosynthesis, gene expression profiles of human monocyte-derived iDC and mDC were
      compared using a gene microarray and quantitative real-time PCR. This gene
      expression profiling showed a profound maturation-induced up-regulation of the
      glycosyltransferases involved in the expression of LacNAc, core 1 and sialylated
      structures and a down-regulation of genes involved in the synthesis of core 2 O
      glycans. Glycosylation changes during DC maturation were corroborated by mass
      spectrometric analysis of N- and O-glycans and by flow cytometry using plant
      lectins and glycan-specific Abs. Interestingly, the binding of the LacNAc
      specific lectins galectin-3 and -8 increased during maturation and up-regulation
      of sialic acid expression by mDC correlated with an increased binding of siglec
      1, -2, and -7.

PMID- 18056366
TI  - Latent membrane protein 1 of EBV activates phosphatidylinositol 3-kinase to
      induce production of IL-10.
AB  - EBV is a B lymphotrophic gamma-herpesvirus that is associated with multiple human
      malignancies, including posttransplant lymphoproliferative disorder. The EBV
      encoded protein, latent membrane protein 1 (LMP1), is required for oncogenic
      transformation of human B cells by EBV. An important consequence of LMP1
      expression in EBV-infected B cells is the induction of cellular IL-10, which acts
      as an autocrine growth factor for B cell lymphomas. However, the mechanisms by
      which LMP1 induces IL-10 are incompletely understood. We previously showed that
      rapamycin, a clinically relevant immunosuppressant and mammalian target of
      rapamycin inhibitor, could suppress IL-10 production by EBV-infected B cell
      lines. To test the hypothesis that PI3K, which acts upstream of mammalian target
      of rapamycin, might also be involved in LMP1-dependent IL-10 production, we
      generated B cell lines expressing signaling-inducible chimeric LMP1. Our results
      show that induced LMP1 signaling elicits both p38- and PI3K-dependent IL-10
      production in EBV- B cells. Moreover, distinct regions of the LMP1 signaling tail
      are associated with p38- vs PI3K-dependent IL-10 induction. We also demonstrate
      that the LMP1-dependent p38 and PI3K activation regulates IL-10 induction through
      discrete mechanisms. Whereas p38 activation is critical for the phosphorylation
      of the transcription factor CREB, PI3K activation is required for the
      inactivation of glycogen synthase kinase 3beta (GSK3beta), an inhibitory kinase
      that can regulate CREB function. We find that GSK3beta regulates LMP1-dependent
      IL-10 induction, with GSK3beta inhibition by pharmacologic or small interfering
      RNA strategies enhancing LMP1-induced IL-10 induction. These findings demonstrate
      that LMP1 uses both p38 and PI3K activation for maximal up-regulation of IL-10.

PMID- 18056367
TI  - Molecular regulation of MHC class I chain-related protein A expression after HDAC
      inhibitor treatment of Jurkat T cells.
AB  - In this study, we characterize the molecular signal pathways that lead to MHC
      class I chain-related protein A (MICA) expression after histone deacetylase
      (HDAC)-inhibitor (HDAC-i) treatment of Jurkat T cells. Chelating calcium with
      BAPTA-AM or EGTA potently inhibited HDAC- and CMV-mediated MICA/B expression. It
      was further observed that endoplasmic reticulum calcium stores were depleted
      after HDAC treatment. NF-kappaB activity can be induced by HDAC treatment.
      However, nuclear translocation of NF-kappaB p65 was not observed after HDAC
      treatment of Jurkat T cells and even though we could effectively inhibit p65
      expression by siRNA, it did not modify MICA/B expression. To identify important
      elements in MICA regulation, we made a promoter construct consisting of
      approximately 3 kb of the proximal MICA promoter in front of GFP. Deletion
      analysis showed that a germinal center-box containing a putative Sp1 site from
      position -113 to -93 relative to the mRNA start site was important for HDAC and
      CMV-induced promoter activity. Sp1 was subsequently shown to be important, as
      targeted mutation of the Sp1 binding sequence or siRNA mediated down modulation
      of Sp1-inhibited MICA promoter activity and surface-expression.

PMID- 18056368
TI  - CD4 T cells are required for CD8 T cell survival during both primary and memory
      recall responses.
AB  - The role of CD4 T cell help in primary and secondary CD8 T cell responses to
      infectious pathogens remains incompletely defined. The primary CD8 T response to
      infections was initially thought to be largely independent of CD4 T cells, but it
      is not clear why some primary, pathogen-specific CD8 T cell responses are CD4 T
      cell dependent. Furthermore, although the generation of functional memory CD8 T
      cells is CD4 T cell help dependent, it remains controversial when the "help" is
      needed. In this study, we demonstrated that CD4 T cell help was not needed for
      the activation and effector differentiation of CD8 T cells during the primary
      response to vaccinia virus infection. However, the activated CD8 T cells showed
      poor survival without CD4 T cell help, leading to a reduction in clonal expansion
      and a diminished, but stable CD8 memory pool. In addition, we observed that CD4 T
      cell help provided during both the primary and secondary responses was required
      for the survival of memory CD8 T cells during recall expansion. Our study
      indicates that CD4 T cells play a crucial role in multiple stages of CD8 T cell
      response to vaccinia virus infection and may help to design effective vaccine
      strategies.

PMID- 18056369
TI  - 4-1BBL induces TNF receptor-associated factor 1-dependent Bim modulation in human
      T cells and is a critical component in the costimulation-dependent rescue of
      functionally impaired HIV-specific CD8 T cells.
AB  - During chronic infection, HIV-specific CD8 T cells exhibit progressive signs of
      functional impairment, attributed to persistent antigenic stimulation, up
      regulation of the inhibitory receptor PD-1, and declining T cell help. Strategies
      that directly improve CD8 T cell function offer the potential of restoring immune
      control of HIV. Although PD-1 expression has been identified as a cause of
      functional impairment in HIV, in this study, PD-1 expression was observed on only
      a subfraction of HIV-specific CD8 T cells in a subfraction of donors, whereas HIV
      specific CTL from all donors exhibited a limited repertoire of effector
      functions. CD137L (4-1BBL) is emerging as an important stimulator of antiviral
      CD8 T cell responses. Regardless of the PD-1 status of the donors, here we show
      that 4-1BBL, when combined with CD80 or CD70, expands a population of Ag-specific
      CD8 T cells expressing multiple markers of effector function, from the
      functionally impaired starting population. In contrast, CD70 in combination with
      CD80 was insufficient for these effects and the related TNF family ligand, LIGHT,
      had negligible activity. The unique contribution of 4-1BBL correlated with down
      regulation of the proapoptotic molecule Bim in activated CD8 T cells. Decreasing
      the level of TNFR-associated factor 1 in T cells using small interfering RNA
      resulted in increased levels of Bim in the 4-1BBL-stimulated T cells. Thus,
      costimulation via 4-1BBL leads to TNFR-associated factor 1-dependent Bim down
      modulation in T cells, resulting in increased T cell expansion. These studies
      identify 4-1BBL as a critical component in therapeutic strategies aimed at
      improving CD8 T cell function.

PMID- 18056370
TI  - Influence of a single viral epitope on T cell response and disease after
      infection of mice with respiratory syncytial virus.
AB  - CTL are important for virus clearance but also contribute to immunopathology
      after the infection of BALB/c mice with respiratory syncytial virus (RSV). The
      pulmonary immune response to RSV is dominated by a CTL population directed
      against the CTL epitope M2-1 82-90. Infection with a virus carrying an M2-1 N89A
      mutation introduced by reverse genetics failed to activate this immunodominant
      CTL population, leading to a significant decrease in the overall antiviral CTL
      response. There was no compensatory increase in responses to the mutated epitope,
      to the subdominant epitope F 85-93, or to yet undefined minor epitopes in the N
      or the P protein. However, there was some increase in the response to the
      subdominant epitope M2-1 127-135, which is located in the same protein and
      presented by the same H-2Kd MHC molecule. Infection with the mutant virus
      reversed the oligoclonality of the T cell response elicited by the wild-type
      virus. These changes in the pattern and composition of the antiviral CTL response
      only slightly impaired virus clearance but significantly reduced RSV-induced
      weight loss. These data illustrate how T cell epitope mutations can influence the
      virus-host relationship and determine disease after an acute respiratory virus
      infection.

PMID- 18056371
TI  - IL-23 is required for neutrophil homeostasis in normal and neutrophilic mice.
AB  - IL-23 is secreted by macrophages and dendritic cells in response to microbial
      products and inflammatory cytokines. IL-23 is a heterodimer composed of the
      unique IL-23p19 subunit linked to the common p40 subunit that it shares with IL
      12. IL-23 is implicated in autoimmune diseases, where it supports the expansion
      of IL-17A-producing CD4+ Th17 cells. IL-23 also regulates granulopoiesis in a
      neutrostat regulatory feedback loop through IL-17A-producing neutrophil
      regulatory (Tn) cells, most of which express gammadelta TCR. This homeostatic
      system is disrupted in mice lacking adhesion molecules like beta2-integrins
      (Itgb2-/-) which have defective neutrophil trafficking and neutrophilia. To test
      the role of IL-23 in the homeostatic regulation of circulating neutrophil
      numbers, we measured blood neutrophil numbers in p40-deficient (IL12b-/-) mice
      and found them reduced compared with wild-type mice. IL12b-/-Itgb2-/- mice,
      lacking beta2-integrins, IL-12, and IL-23 showed significantly blunted
      neutrophilia compared with Itgb2-/- mice. Treatment of both IL12b-/- and IL12b-/
      Itgb2-/- mice with IL-23, but not IL-12, restored circulating neutrophil counts.
      Serum levels of IL-17A were readily detectable in Itgb2-/- mice, but not in IL12b
      /-Itgb2-/- mice, suggesting that IL-17A production is reduced when IL-23 is
      absent. Similarly, tissue mRNA expression of IL-17A was reduced in IL12b-/-Itgb2
      /-mice compared with Itgb2-/- controls. The total number of CD3+ IL-17A-producing
      Tn cells were significantly reduced in the spleen and lamina propria of IL12b-/
      Itgb2-/- mice, with the largest reduction found in gammadelta+ T cells. Our
      results suggest a prominent role of IL-23 in the regulation of granulopoiesis and
      the prevalence of IL-17A-producing Tn cells.

PMID- 18056372
TI  - N-terminal trimer extension of nominal CD8 T cell epitopes is sufficient to
      promote cross-presentation to cognate CD8 T cells in vivo.
AB  - Cross-priming is the process in which Ag-presenting dendritic cells (DCs)
      acquire, process, and present Ags scavenged from other cells, and use these cells
      to activate naive CD8 T cells. Cross-priming of cognate CD8 cells can result in
      either tolerance or immunity, depending upon the activation status of the Ag
      presenting DC. Previous studies have shown that nominal peptide is inefficiently
      cross-presented and that proteins and large polypeptides that require proteasomal
      processing are the main source of naturally cross-presented Ags. In this study we
      show that N-terminal extension of nominal peptide by as few as three residues is
      sufficient to produce a substrate for TAP-dependent cross-presentation that is
      highly efficient in cross-priming murine CD8 T cells in vivo. On a molar basis,
      cross-priming with 3-mer-extended peptide is 20-fold more efficient than priming
      with intact protein. This method of peptide extension should prove of great value
      in facilitating in vivo studies of CD8 immunity and tolerance that rely on cross
      presentation.

PMID- 18056373
TI  - Prolonged (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate-driven antimicrobial
      and cytotoxic responses of pulmonary and systemic Vgamma2Vdelta2 T cells in
      macaques.
AB  - Although phosphoantigen-specific Vgamma2Vdelta2 T cells appear to play a role in
      antimicrobial and anticancer immunity, mucosal immune responses and effector
      functions of these gammadelta T cells during infection or phospholigand treatment
      remain poorly characterized. In this study, we demonstrate that the microbial
      phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) plus IL-2
      treatment of macaques induced a prolonged major expansion of circulating
      Vgamma2Vdelta2 T cells that expressed CD8 and produced cytotoxic perforin during
      their peak expansion. Interestingly, HMBPP-activated Vgamma2Vdelta2 T cells
      underwent an extraordinary pulmonary accumulation, which lasted for 3-4 mo,
      although circulating Vgamma2Vdelta2 T cells had returned to baseline levels weeks
      prior. The Vgamma2Vdelta2 T cells that accumulated in the lung following HMBPP/IL
      2 cotreatment displayed an effector memory phenotype, as follows: CCR5+CCR7
      CD45RA-CD27+ and were able to re-recognize phosphoantigen and produce copious
      amounts of IFN-gamma up to 15 wk after treatment. Furthermore, the capacity of
      massively expanded Vgamma2Vdelta2 T cells to produce cytokines in vivo coincided
      with an increase in numbers of CD4+ and CD8+ alphabeta T cells after HMBPP/IL-2
      cotreatment as well as substantial perforin expression by CD3+Vgamma2- T cells.
      Thus, the prolonged HMBPP-driven antimicrobial and cytotoxic responses of
      pulmonary and systemic Vgamma2Vdelta2 T cells may confer immunotherapeutics
      against infectious diseases and cancers.

PMID- 18056374
TI  - Interaction between GATA-3 and the transcriptional coregulator Pias1 is important
      for the regulation of Th2 immune responses.
AB  - Th2 cytokine expression is dependent on the transcription factor GATA-3. However,
      the molecular interactions of GATA-3 leading to Th2 cytokine gene activation have
      not been well characterized. Here, we reported a number of GATA-3 associated
      proteins in Th2 cells, and one of such proteins Pias1 functioned as a positive
      transcriptional coregulator for GATA-3. When overexpressed in Th2 cells, Pias1
      enhanced the expression of IL-13, and to lesser degrees, IL-4 and -5. Conversely,
      Pias1 siRNA down-regulated the Th2 cytokine expression. In Leishmania major
      infection, manipulating Pias1 expression in parasite-reactive CD4 T cells altered
      severity of disease caused by Th2 responses. Mechanistically, Pias1 markedly
      potentiated GATA-3-mediated activation of the IL-13 promoter by facilitating the
      recruitment of GATA-3 to the promoter. In contrast, IL-5 promoter was modestly
      enhanced by Pias1 and no effect was observed on IL-4 promoter. Thus, both
      promoter activation and additional mechanisms are responsible for regulation by
      Pias1.

PMID- 18056375
TI  - Physiological fever temperature induces a protective stress response in T
      lymphocytes mediated by heat shock factor-1 (HSF1).
AB  - Heat shock factor-1 (HSF1) is a transcription factor that serves as the major
      temperature-inducible sensor for eukaryotic cells. In most cell types, HSF1
      becomes activated to the DNA binding form at 42 degrees C and mediates the
      classical heat shock response, protecting the cells from subsequent lethal
      temperatures. We have recently demonstrated that HSF1 is activated at a lower
      temperature in T lymphocytes than in most other cell types (39 degrees C vs 42
      degrees C), within the physiological range of fever. In this study, we show that
      T cell activation at fever temperatures not only activates HSF1 but induces the
      up-regulation of the HSF1 protein and the HSF1-regulated protein, HSP70i. T cells
      from HSF1 knockout mice proliferate normally under optimal conditions but are
      impaired in proliferation at physiological fever temperatures and low CO2
      concentrations, conditions that do not impair wild-type T cells. This defect in
      proliferation appears to be mediated by a block in the G1/S transition of the
      cell cycle and is independent of HSP70. Elevated temperature and low CO2
      concentrations resulted in a dramatic reduction of the intracellular reactive
      oxygen species (ROS) levels in both normal and knockout T cells. Wild-type T
      cells were able to restore ROS levels to normal within 5 h, whereas HSF1-/- T
      cells were not. These results suggest that the proliferation defect seen in T
      cells from HSF1-/- mice at fever temperatures was because of dysregulated ROS
      levels and that HSF1 is important in maintaining ROS homeostasis and cell cycle
      progression under the stressful conditions encountered during fever.

PMID- 18056376
TI  - Prolonged antigen expression following DNA vaccination impairs effector CD8+ T
      cell function and memory development.
AB  - After priming, naive T cells undergo a program of expansion, contraction, and
      memory formation. Numerous studies have indicated that only a brief period of
      antigenic stimulation is required to fully commit CD8+ T cells to this program.
      Nonetheless, the persistence of Ag may modulate the eventual fate of CD8+ T
      cells. Using DNA delivery, we showed previously that direct presentation primes
      high levels of effector CD8+ T cells as compared with cross-presentation. One
      explanation now revealed is that prolonged cross-presentation limits effector
      cell expansion and function. To analyze this, we used a drug-responsive system to
      regulate Ag expression after DNA injection. Reducing expression to a single burst
      expanded greater numbers of peptide-specific effector CD8+ T cells than sustained
      Ag. Consequences for memory development were assessed after boosting and showed
      that, although persistent Ag maintained higher numbers of tetramer-positive CD8+
      T cells, these expanded less (approximately 4-fold) than those induced by
      transient Ag expression (approximately 35-fold). Transient expression at priming
      therefore led to a net higher secondary response. In terms of vaccine design, we
      propose that the most effective DNA-based CD8+ T cell vaccines will be those that
      deliver a short burst of Ag.

PMID- 18056378
TI  - Biochemical and folding defects in a RAG1 variant associated with Omenn syndrome.
AB  - The RAG1 and RAG2 proteins are required to assemble mature Ag receptor genes in
      developing lymphocytes. Hypomorphic mutations in the gene encoding RAG1 are
      associated with Omenn syndrome, a primary immunodeficiency. We explored the
      biochemical defects resulting from a mutation identified in an Omenn syndrome
      patient which generates an amino acid substitution in the RAG1 RING
      finger/ubiquitin ligase domain (C325Y in murine RAG1) as well as an adjacent
      substitution (P326G). RAG1 C325Y demonstrated a 50-fold reduction in
      recombination activity in cultured pro-B cells despite the fact that its
      expression and localization to the nucleus were similar to the wild-type protein.
      The C325Y substitution severely abrogated ubiquitin ligase activity of the
      purified RAG1 RING finger domain, and the tertiary structure of the domain was
      altered. The P326G substitution also abrogated ubiquitin ligase activity but had
      a less severe effect on protein folding. RAG1 P326G also demonstrated a
      recombination impairment that was most pronounced when RAG1 levels were limiting.
      Thus, a correctly folded RAG1 RING finger domain is required for normal V(D)J
      recombination, and RAG1 ubiquitin ligase activity can contribute when the protein
      is present at relatively low levels.

PMID- 18056377
TI  - Rap1a null mice have altered myeloid cell functions suggesting distinct roles for
      the closely related Rap1a and 1b proteins.
AB  - The Ras-related GTPases Rap1a and 1b have been implicated in multiple biological
      events including cell adhesion, free radical production, and cancer. To gain a
      better understanding of Rap1 function in mammalian physiology, we deleted the
      Rap1a gene. Although loss of Rap1a expression did not initially affect mouse size
      or viability, upon backcross into C57BL/6J mice some Rap1a-/- embryos died in
      utero. T cell, B cell, or myeloid cell development was not disrupted in Rap1a-/-
      mice. However, macrophages from Rap1a null mice exhibited increased haptotaxis on
      fibronectin and vitronectin matrices that correlated with decreased adhesion.
      Chemotaxis of lymphoid and myeloid cells in response to CXCL12 or CCL21 was
      significantly reduced. In contrast, an increase in FcR-mediated phagocytosis was
      observed. Because Rap1a was previously copurified with the human neutrophil NADPH
      oxidase, we addressed whether GTPase loss affected superoxide production.
      Neutrophils from Rap1a-/- mice had reduced fMLP-stimulated superoxide production
      as well as a weaker initial response to phorbol ester. These results suggest
      that, despite 95% amino acid sequence identity, similar intracellular
      distribution, and broad tissue distribution, Rap1a and 1b are not functionally
      redundant but rather differentially regulate certain cellular events.

PMID- 18056379
TI  - Interactions between Idd5.1/Ctla4 and other type 1 diabetes genes.
AB  - Two loci, Idd5.1 and Idd5.2, that determine susceptibility to type 1 diabetes
      (T1D) in the NOD mouse are on chromosome 1. Idd5.1 is likely accounted for by a
      synonymous single nucleotide polymorphism in exon 2 of Ctla4: the B10-derived T1D
      resistant allele increases the expression of the ligand-independent isoform of
      CTLA-4 (liCTLA-4), a molecule that mediates negative signaling in T cells. Idd5.2
      is probably Nramp1 (Slc11a1), which encodes a phagosomal membrane protein that is
      a metal efflux pump and is important for host defense and Ag presentation. In
      this study, two additional loci, Idd5.3 and Idd5.4, have been defined to 3.553
      and 78 Mb regions, respectively, on linked regions of chromosome 1. The most
      striking findings, however, concern the evidence we have obtained for strong
      interactions between these four disease loci that help explain the association of
      human CTLA4 with T1D. In the presence of a susceptibility allele at Idd5.4, the
      CTLA-4 resistance allele causes an 80% reduction in T1D, whereas in the presence
      of a protective allele at Idd5.4, the effects of the resistance allele at Ctla4
      are modest or, as in the case in which resistance alleles at Idd5.2 and Idd5.3
      are present, completely masked. This masking of CTLA-4 alleles by different
      genetic backgrounds provides an explanation for our observation that the human
      CTLA-4 gene is only associated with T1D in the subgroup of human T1D patients
      with anti-thyroid autoimmunity.

PMID- 18056380
TI  - Activation of phosphatase and tensin homolog on chromosome 10 mediates the
      inhibition of FcgammaR phagocytosis by prostaglandin E2 in alveolar macrophages.
AB  - PGE2 has important inhibitory effects on the macrophage host defense functions of
      phagocytosis and killing, yet the molecular mechanisms involved remain to be
      fully elucidated. PGE2 causes an elevation of cAMP in alveolar macrophages (AMs),
      which in turn activates the cAMP effector targets, protein kinase A and the
      exchange protein activated by cAMP (Epac)-1. We now report that FcgammaR-induced
      PI3K/Akt and ERK-1/2 activation are inhibited by PGE2 in AMs. By specifically
      inhibiting the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in
      AMs, we attenuated the inhibitory effects of both PGE2 and a specific Epac-1
      agonist (8-pCPT-2'-O-Me-cAMP) on FcgammaR-mediated phagocytosis and Akt/ERK-1/2
      activation; PTEN inhibition also decreased PGE2-induced suppression of bacterial
      killing by AMs. Moreover, PGE2 and the Epac-1 agonist induced an increase in PTEN
      lipid phosphatase activity, and this was associated with decreased tyrosine
      phosphorylation on PTEN-a mechanism known to regulate PTEN activity. Using a
      pharmacological approach, we demonstrated a role for Src homology 2-containing
      protein tyrosine phosphatase-1 in the PGE2-induced tyrosine dephosphorylation of
      PTEN. Collectively, these data reveal that PGE2, via Epac-1 activation, enhances
      SHP-1 activity, resulting in increased PTEN activity. We suggest that this
      mechanism contributes to the ability of PGE2 to inhibit PI3K-dependent innate
      immune signaling in primary macrophages.

PMID- 18056381
TI  - Death receptor ligation or exposure to perforin trigger rapid egress of the
      intracellular parasite Toxoplasma gondii.
AB  - The obligate intracellular parasite Toxoplasma gondii chronically infects up to
      one-third of the global population, can result in severe disease in
      immunocompromised individuals, and can be teratogenic. In this study, we
      demonstrate that death receptor ligation in T. gondii-infected cells leads to
      rapid egress of infectious parasites and lytic necrosis of the host cell, an
      active process mediated through the release of intracellular calcium as a
      consequence of caspase activation early in the apoptotic cascade. Upon acting on
      infected cells via death receptor- or perforin-dependent pathways, T cells induce
      rapid egress of infectious parasites able to infect surrounding cells, including
      the Ag-specific effector cells.

PMID- 18056382
TI  - Analysis of the 5q31 33 locus shows an association between single nucleotide
      polymorphism variants in the IL-5 gene and symptomatic infection with the human
      blood fluke, Schistosoma japonicum.
AB  - Genetic studies of human susceptibility to Schistosoma (blood fluke) infections
      have previously identified a genetic locus determining infection intensity with
      the African species, Schistosoma mansoni, in the 5q31-33 region of the human
      genome that is known to contain the Th2 immune response cluster, including the
      genes encoding the IL-4, IL-5, and IL-13 cytokines. These cytokines are key
      players in inflammatory immune responses and have previously been implicated in
      human susceptibility to infection with the Asian species, S. japonicum. In a
      nested case control study, we genotyped 30 HapMap tagging single nucleotide
      polymorphisms (SNPs) across these three genes in 159 individuals identified as
      putatively susceptible to reinfection with S. japonicum and in 133 putatively
      resistant individuals. A third group comprising 113 individuals demonstrating
      symptomatic infection was also included. The results provided no significant
      association at a global level between reinfection predisposition and any of the
      individual SNPs or haplotype blocks. However, two tagging SNPs in IL-5
      demonstrated globally significant association with susceptibility to symptomatic
      infection. They were in strong linkage disequilibrium with each other and were
      found to belong to the same haplotype block that also provided a significant
      association after permutation testing. This haplotype was located in the 3'
      untranslated region of IL-5, suggesting that variants in this region of IL-5 may
      modulate the immune response in these individuals with symptomatic infection.

PMID- 18056383
TI  - Mechanisms of vaccine-induced protective immunity against Coxiella burnetii
      infection in BALB/c mice.
AB  - To elucidate the mechanisms of vaccine-induced protective immunity against
      Coxiella burnetii infection, we compared the protective efficacy and
      immunogenicity between formalin-inactivated phase I vaccine (PI-V) and phase II
      vaccine (PII-V) in BALB/c mice. PI-V generated significant protection while PII-V
      did not confer measurable protection. Analysis of cytokine and subclass Ab
      responses indicated that both PI-V and PII-V were able to induce a Th1-dominant
      immune response but did not identify the component of host response that
      distinguished their ability to induce protective immunity. Interestingly,
      immunoblot analysis identified a difference between PI-V and PII-V vaccinates in
      antigenic recognition by specific Ab isotypes. The observation that PI-LPS
      elicited significant protection but PII-LPS did not confer measurable protection
      suggests PI-LPS may play a key role in PI-V-induced protection. Adoptive transfer
      of either immune sera or splenocytes mediated significant protection in naive
      BALB/c mice, supporting the notion that both humoral and cellular immunity are
      important for development of protective immunity. However, the evidence that
      immune sera and B cells were unable to control infection while T cells conferred
      significant protection in SCID mice supports the hypothesis that T cell-mediated
      immunity is critical for host defense against C. burnetii infection. This report
      presents novel evidence to highlight the importance of PI-LPS and Abs in
      protective immunity and has important implications for the design of new
      generation vaccines against Q fever.

PMID- 18056384
TI  - Mycobacterium tuberculosis antigens specifically modulate CCR2 and MCP-1/CCL2 on
      lymphoid cells from human pulmonary hilar lymph nodes.
AB  - Macrophages and dendritic cells are involved in the immune response to
      Mycobacterium tuberculosis (Mtb). Such a response, although extensively studied
      using animal models and cells from human blood, has not been characterized in
      cells from pulmonary hilar lymph nodes (PHLN). We characterized populations of
      myeloid APC from PHLN and determined their expression of CCR2, CCR5, CCR7, CD40,
      CD54, CD80, and CD86 as well as the cytokine/chemokine microenvironment before
      and after purified protein derivative (PPD) and mannosilated lipoarabinomannan
      (ManLAM) stimulation. Results show that there are at least three APC populations
      in PHLN, defined as CD14highHLA-DRlow/-, CD14dimHLA-DRdim, and CD14-HLA
      DRhigh/dendritic cells (DC), with the largest number represented by CD14dimHLA
      DRdim cells (where dim indicates intermediate levels). CD14-HLA-DRhigh/DC
      expressed higher levels of costimulatory molecules and lower levels of CCR2 and
      CCR5, but all cell populations showed similar CCR7 levels. PPD and ManLAM
      specifically down-regulated CCR2 expression but not that of CCR5 and CCR7, and
      such down-regulation was observed on all APC populations. Mtb Ag did not affect
      the expression of costimulatory molecules. PPD but not ManLAM specifically
      induced MCP-1/CCL2 production, which was likely associated with the induction of
      IFN-gamma because this cytokine was highly induced by PPD. We characterized, for
      the first time, different APC from human PHLN and show that Mtb Ag exert fine and
      specific regulation of molecules closely associated with the immune response to
      Mtb infection. Because knowledge of this response in secondary lymphoid tissues
      is still poorly understood in humans, such studies are necessary and important
      for a better understanding of lymphoid cell microenvironment and migrating
      capacities and their role in the immunopathogenesis of tuberculosis.

PMID- 18056385
TI  - A replication-deficient murine gamma-herpesvirus blocked in late viral gene
      expression can establish latency and elicit protective cellular immunity.
AB  - The human gamma-herpesviruses, EBV and Kaposi's sarcoma-associated herpesvirus,
      are widely disseminated and are associated with the onset of a variety of
      malignancies. Thus, the development of prophylactic and therapeutic vaccination
      strategies is an important goal. The experimental mouse gamma-herpesvirus,
      gammaHV68 (or MHV-68), has provided an in vivo model for studying immune control
      of these persistent viruses. In the current studies, we have examined
      infectivity, immunogenicity, and protective efficacy following infection with a
      replication-deficient gammaHV68 blocked in late viral gene expression, ORF31STOP.
      The data show that ORF31STOP was able to latently infect B cells. However, the
      anatomical site and persistence of the infection depended on the route of
      inoculation, implicating a role for viral replication in viral spread but not the
      infectivity per se. Furthermore, i.p. infection with ORF31STOP elicited strong
      cellular immunity but a non-neutralizing Ab response. In contrast, intranasal
      infection was poorly immunogenic. Consistent with this, mice infected i.p. had
      enhanced control of both the lytic and latent viral loads following challenge
      with wild-type gammaHV68, whereas intranasal infected mice were not protected.
      These data provide important insight into mechanisms of infection and protective
      immunity for the gamma-herpesviruses and demonstrate the utility of replication
      deficient mutant viruses in direct testing of "proof of principal" vaccination
      strategies.

PMID- 18056386
TI  - West Nile virus envelope protein inhibits dsRNA-induced innate immune responses.
AB  - The immune response against viral infection relies on the early production of
      cytokines that induce an antiviral state and trigger the activation of immune
      cells. This response is initiated by the recognition of virus-associated
      molecular patterns such as dsRNA, a viral replication intermediate recognized by
      TLR3 and certain RNA helicases. Infection with West Nile virus (WNV) can lead to
      lethal encephalitis in susceptible individuals and constitutes an emerging health
      threat. In this study, we report that WNV envelope protein (WNV-E) specifically
      blocks the production of antiviral and proinflammatory cytokines induced by dsRNA
      in murine macrophages. This immunosuppressive effect was not dependent on TLR3 or
      its adaptor molecule Trif. Instead, our experiments show that WNV-E acts at the
      level of receptor-interacting protein 1. Our results also indicate that WNV-E
      requires a certain glycosylation pattern, specifically that of dipteran cells, to
      inhibit dsRNA-induced cytokine production. In conclusion, these data show that
      the major structural protein of WNV impairs the innate immune response and
      suggest that WNV exploits differential vector/host E glycosylation profiles to
      evade antiviral mechanisms.

PMID- 18056387
TI  - CD8+ T cell responses in bronchoalveolar lavage fluid and peripheral blood
      mononuclear cells of infants with severe primary respiratory syncytial virus
      infections.
AB  - A protective role for CD8+ T cells during viral infections is generally accepted,
      but little is known about how CD8+ T cell responses develop during primary
      infections in infants, their efficacy, and how memory is established after viral
      clearance. We studied CD8+ T cell responses in bronchoalveolar lavage (BAL)
      samples and blood of infants with a severe primary respiratory syncytial virus
      (RSV) infection. RSV-specific CD8+ T cells with an activated effector cell
      phenotype: CD27+CD28+CD45RO+CCR7-CD38+HLA-DR+Granzyme B+CD127- could be
      identified in BAL and blood. A high proportion of these CD8+ T cells proliferated
      and functionally responded upon in vitro stimulation with RSV Ag. Thus, despite
      the very young age of the patients, a robust systemic virus-specific CD8+ T cell
      response was elicited against a localized respiratory infection. RSV-specific T
      cell numbers as well as the total number of activated effector type CD8+ T cells
      peaked in blood around day 9-12 after the onset of primary symptoms, i.e., at the
      time of recovery. The lack of a correlation between RSV-specific T cell numbers
      and parameters of disease severity make a prominent role in immune pathology
      unlikely, in contrast the T cells might be involved in the recovery process.

PMID- 18056388
TI  - Improved protection against disseminated tuberculosis by Mycobacterium bovis
      bacillus Calmette-Guerin secreting murine GM-CSF is associated with expansion and
      activation of APCs.
AB  - Modulating the host-immune response by the use of recombinant vaccines is a
      potential strategy to improve protection against microbial pathogens. In this
      study, we sought to determine whether secretion of murine GM-CSF by the bacillus
      Calmette-Guerin (BCG) vaccine influenced protective immunity against
      Mycobacterium tuberculosis. BCG-derived GM-CSF stimulated the in vitro generation
      of functional APCs from murine bone marrow precursors, as demonstrated by the
      infection-induced secretion of IL-12 by differentiated APCs, and the ability of
      these cells to present Ag to mycobacterium-specific T cells. Mice vaccinated with
      BCG secreting [corrected] murine GM-CSF (BCG:GM-CSF) showed increased numbers of
      CD11c+MHCII+ and CD11c-CD11b+F480+ cells compared with those vaccinated with
      control BCG, and this effect was most apparent in the draining lymph nodes at 7
      and 14 days postvaccination. Vaccination with BCG:GM-CSF also resulted in
      enhanced expression of costimulatory molecules on migratory dendritic cells in
      the draining lymph nodes. The increased APC number was associated with an
      increase in the frequency of anti-mycobacterial IFN-gamma-secreting T cells
      generated after BCG:GM-CSF vaccination compared with vaccination with control
      BCG, and this effect was sustained up to 17 wk in the spleens of immunized mice.
      Vaccination with BCG:GM-CSF resulted in an approximately 10-fold increase in
      protection against disseminated M. tuberculosis infection compared with control
      BCG. This study demonstrates the potential of BCG secreting [corrected]
      immunostimulatory molecules as vaccines to protect against tuberculosis and
      suggests BCG:GM-CSF merits further appraisal as a candidate to control M.
      tuberculosis infection in humans.

PMID- 18056389
TI  - A short-form C-type lectin from amphioxus acts as a direct microbial killing
      protein via interaction with peptidoglycan and glucan.
AB  - To investigate the evolution and immune function of C-type lectin in amphioxus,
      the primitive representative of the chordate phylum, we identified three C-type
      lectins consisting solely of a carbohydrate recognition domain and N-terminal
      signal peptide and found that they had distinct express patterns in special
      tissues and immune response to stimulations analyzed by quantitative real-time
      PCR. We characterized the biochemical and biological properties of AmphiCTL1,
      which was dramatically up-regulated in amphioxus challenged with Staphylococcus
      aureus, Saccharomyces cerevisiae, and zymosan. Immunohistochemistry demonstrated
      that the localization of AmphiCTL1 protein was exclusively detected in the inner
      folding tissues of the hepatic diverticulum. Recombinant AmphiCTL1 was
      characterized as a typical Ca2+-dependent carbohydrate-binding protein possessing
      hemagglutinating activity, preferentially bound to all examined four Gram
      positive bacteria and two yeast strains, but had little binding activity toward
      four Gram-negative bacteria we tested. It aggregated S. aureus and S. cerevisiae
      in a Ca2+-dependent manner and specifically bound to insoluble peptidoglycan and
      glucan, but not to LPS, lipoteichoic acid, and mannan. Calcium increased the
      intensity of the interaction between AmphiCTL1 and those components, but was not
      essential. This lectin directly killed S. aureus and S. cerevisiae in a Ca2+
      independent fashion, and its binding to microorganism cell wall polysaccharides
      such as peptidoglycan and glucan preceded microbial killing activity. These
      findings suggested that AmphiCTL1 acted as a direct microbial killing C-type
      lectin through binding microbial targets via interaction with peptidoglycan and
      glucan. Thus, AmphiCTL1 may be an evolutionarily primitive form of antimicrobial
      protein involved in lectin-mediated innate immunity.

PMID- 18056390
TI  - Candida albicans triggers activation of distinct signaling pathways to establish
      a proinflammatory gene expression program in primary human endothelial cells.
AB  - Endothelial cells (EC) actively participate in the innate defense against
      microbial pathogens. Under unfavorable conditions, defense reactions can turn
      life threatening resulting in sepsis. We therefore studied the so far largely
      unknown EC reaction patterns to the fungal pathogen Candida albicans, which is a
      major cause of lethality in septic patients. Using oligonucleotide microarray
      analysis, we identified 56 genes that were transcriptionally up-regulated and 69
      genes that were suppressed upon exposure of ECs to C. albicans. The most
      significantly up-regulated transcripts were found in gene ontology groups
      comprising the following categories: chemotaxis/migration; cell death and
      proliferation; signaling; transcriptional regulation; and cell-cell
      contacts/intercellular signaling. Further examination of candidate signaling
      cascades established a central role of the proinflammatory NF-kappaB pathway in
      the regulation of the Candida-modulated transcriptome of ECs. As a second major
      regulatory pathway we identified the stress-activated p38 MAPK pathway, which
      critically contributes to the regulation of selected Candida target genes such as
      CXCL8/IL-8. Depletion of MyD88 and IL-1R-associated kinase-1 by RNA interference
      demonstrates that Candida-induced NF-kappaB activation is mediated by pattern
      recognition receptor signaling. Additional experiments suggest that C. albicans
      induced CXCL8/IL-8 expression is mediated by TLR3 rather than TLR2 and TLR4,
      which previously have been implicated with MyD88/IkappaB kinase-2/NF-kappaB
      activation by this fungus in other systems. Our study provides the first
      comprehensive analysis of endothelial gene responses to C. albicans and presents
      novel insights into the complex signaling patterns triggered by this important
      pathogen.

PMID- 18056391
TI  - An effect of parasite-encoded arginase on the outcome of murine cutaneous
      leishmaniasis.
AB  - Classical activation of macrophages infected with Leishmania species results in
      expression and activation of inducible NO synthase (iNOS) leading to
      intracellular parasite killing. Macrophages can contrastingly undergo alternative
      activation with increased arginase activity, metabolism of arginine along the
      polyamine pathway, and consequent parasite survival. An active role for parasite
      encoded arginase in host microbicidal responses has not previously been
      documented. To test the hypothesis that parasite-encoded arginase can influence
      macrophage responses to intracellular Leishmania, a comparative genetic approach
      featuring arginase-deficient mutants of L. mexicana lacking both alleles of the
      gene encoding arginase (Deltaarg), as well as wild-type and complemented Deltaarg
      controls (Deltaarg[pArg]), was implemented. The studies showed: 1) the absence of
      parasite arginase resulted in a significantly attenuated infection of mice
      (p<0.05); 2) poorer survival of Deltaarg in mouse macrophages than controls
      correlated with greater NO generation; 3) the difference between Deltaarg or
      control intracellular survival was abrogated in iNOS-deficient macrophages,
      suggesting iNOS activity was responsible for increased Deltaarg killing; 4)
      consistently, immunohistochemistry showed enhanced nitrotyrosine modifications in
      tissues of mice infected with Deltaarg compared with control parasites.
      Furthermore, 5) in the face of decreased parasite survival, lymph node cells
      draining cutaneous lesions of Deltaarg parasites produced more IFN-gamma and less
      IL-4 and IL-10 than controls. These data intimate that parasite-encoded arginase
      of Leishmania mexicana subverts macrophage microbicidal activity by diverting
      arginine away from iNOS.

PMID- 18056392
TI  - CD66b regulates adhesion and activation of human eosinophils.
AB  - Eosinophils and their products are likely important in the pathophysiology of
      allergic diseases, such as bronchial asthma, and in host immunity to parasitic
      organisms. However, the mechanisms for proinflammatory mediator release by
      eosinophils are poorly understood. CD66b (CEACAM8, CGM6, NCA-95) is a single
      chain, GPI-anchored, highly glycosylated protein belonging to the
      carcinoembryonic Ag supergene family. CD66b is an activation marker for human
      granulocytes; however, its biological functions are largely unknown in
      eosinophils. We found that CD66b is highly expressed on the surface of human
      peripheral blood eosinophils isolated from healthy individuals. Engagement of
      CD66b, but not CD66a, by mAb or a natural ligand, galectin-3, activated a Src
      kinase family molecule, hemopoietic cell kinase (Hck), and induced cellular
      adhesion, superoxide production, and degranulation of eosinophils. CD66b
      molecules were localized in lipid rafts, and disruption of lipid rafts or removal
      of the GPI anchor inhibited the adhesion and activation of eosinophils.
      Importantly, CD66b was constitutively and physically associated with a beta2
      integrin, CD11b, and cross-linking of CD66b induced a striking clustering of
      CD11b molecules. Thus, CD66b molecules are involved in regulating adhesion and
      activation of eosinophils, possibly through their localization in lipid rafts and
      interaction with other cell surface molecules, such as CD11b. Binding of
      exogenous or endogenous carbohydrate ligands(s) to CD66b may be important in the
      release of proinflammatory mediators by human eosinophils.

PMID- 18056393
TI  - Blockade of chemokine receptor CXCR3 inhibits T cell recruitment to inflamed
      joints and decreases the severity of adjuvant arthritis.
AB  - T lymphocytes expressing the chemokine receptors, CCR2, CCR5, CXCR3, and CXCR6
      are increased in inflamed tissues in rheumatoid arthritis. The role of CXCR3 in
      autoimmune arthritis induced in Lewis rats was investigated. CXCR3+ T cells
      migrated 2- to 3-fold more than CXCR3- T cells to inflamed joints in arthritic
      animals. CXCR3-expressing in vivo Ag-activated T lymphoblasts and in vitro
      activated lymph node cells from arthritic animals were strongly recruited to the
      arthritic joints, and treatment with anti-CXCR3 mAb significantly inhibited this
      T cell recruitment by 40-60%. Immune T cells from the spleen and lymph nodes of
      actively immunized arthritic donors adoptively transferred arthritis to naive
      rats. Treatment with anti-CXCR3 mAb delayed the onset of arthritis and
      significantly reduced the severity of joint inflammation with a >50% decrease in
      the clinical arthritis score. Blockade of CXCR3 also significantly reduced the
      weight loss in the arthritic animals and inhibited neutrophil accumulation in the
      joints by 50-60%. There was a marked reduction in the leukocyte infiltration of
      the synovium in the presence of CXCR3 blockade and a decrease in the loss of
      articular cartilage of the joints. In conclusion, CXCR3 on T cells has an
      essential role in T cell recruitment to inflamed joints and the development of
      joint inflammation in adjuvant arthritis.

PMID- 18056394
TI  - E- and P-selectin are not required for the development of experimental autoimmune
      encephalomyelitis in C57BL/6 and SJL mice.
AB  - In multiple sclerosis and in its animal model experimental autoimmune
      encephalomyelitis (EAE), inflammatory cells migrate across the endothelial blood
      brain barrier (BBB) and gain access to the CNS. It is well-established that
      alpha4 integrins are actively involved in leukocyte recruitment across the BBB
      during EAE. In contrast, the role of endothelial E- and P-selectin in this
      process has been a controversial issue. In this study, we demonstrate that P
      selectin protein can be detected in meningeal blood vessel endothelial cells in
      healthy SJL and C57BL/6 mice and on rare parenchymal CNS blood vessels in
      C57BL/6, but not SJL, mice. During EAE, expression of P-selectin but not E
      selectin was found up-regulated on inflamed CNS microvessels surrounded by
      inflammatory infiltrates irrespective of their meningeal or parenchymal
      localization with a more prominent immunostaining detected in C57BL/6 as compared
      with SJL mice. P-selectin immunostaining could be localized to CNS endothelial
      cells and to CD41-positive platelets adhering to the vessel wall. Despite the
      presence of P-selectin in wild-type mice, E/P-selectin-deficient SJL and C57BL/6
      mice developed clinical EAE indistinguishable from wild-type mice. Absence of E-
      and P-selectin did neither influence the activation of myelin-specific T cells
      nor the composition of the cellular infiltrates in the CNS during EAE. Finally,
      endothelial-specific tetracycline-inducible expression of E-selectin at the BBB
      in transgenic C57BL/6 mice did not alter the development of EAE. Thus, E- and P
      selectin are not required for leukocyte recruitment across the BBB and the
      development of EAE in C57BL/6 and in SJL mice.

PMID- 18056395
TI  - Caspase-4 interacts with TNF receptor-associated factor 6 and mediates
      lipopolysaccharide-induced NF-kappaB-dependent production of IL-8 and CC
      chemokine ligand 4 (macrophage-inflammatory protein-1 ).
AB  - Human caspase-4 does not have a corresponding mouse ortholog. Caspase-4 falls
      within the class of "inflammatory caspases," being homologous with human caspases
      1 and 5 and mouse caspases 1, 11, and 12. To address the function of caspase-4,
      we generated caspase-4-deficient human THP1 monocytic cell lines which exhibited
      substantially reduced LPS-induced secretion of several chemokines and cytokines,
      including IL-8 (CXCL8), CCL4 (macrophage-inflammatory protein-1beta), CCL20
      (macrophage-inflammatory protein-3alpha), and IL-1beta. The LPS-induced
      expression of the mRNAs encoding these cytokines was correspondingly reduced in
      the caspase-4-deficient clones. Because a specific NF-kappaB inhibitor blocked
      LPS-induced IL-8 and CCL4 mRNA expression as well as IL-8 and CCL4 secretion in
      THP1 cells, we investigated the role of caspase-4 in NF-kappaB signaling. LPS
      induced NF-kappaB nuclear translocation and activation were inhibited in all
      caspase-4-deficient clones. LPS stimulation led to the interaction of endogenous
      caspase-4 and TNFR-associated factor 6 (TRAF6) via a TRAF6-binding motif
      (PPESGE), which we identified in caspase-4. Mutation of this site in caspase-4
      resulted in the loss of the TRAF6-caspase-4 interaction. Similar TRAF6-binding
      motifs are known to be functionally important for TRAF6 interactions with other
      molecules including caspase-8, and for mediating NF-kappaB activation in various
      immune and nonimmune cell types. Our data suggest that the TRAF6-caspase-4
      interaction, triggered by LPS, leads to NF-kappaB-dependent transcriptional up
      regulation and secretion of important cytokines and chemokines in innate immune
      signaling in human monocytic cells.

PMID- 18056396
TI  - Pulmonary and systemic endotoxin tolerance in preterm fetal sheep exposed to
      chorioamnionitis.
AB  - In a model of human chorioamnionitis, fetal sheep exposed to a single injection,
      but not repeated injections, of intra-amniotic endotoxin develop lung injury
      responses. We hypothesized that repeated exposure to intra-amniotic endotoxin
      induces endotoxin tolerance. Fetal sheep were given intra-amniotic injections of
      saline (control) or Escherichia coli LPS O55:B5 (10 mg) either 2 days (2-day
      group, single exposure), 7 days (7-day group, single exposure), or 2 plus 7 days
      (2- and 7-day repeat exposure) before preterm delivery at 124 days gestation
      (term=150 days). Endotoxin responses were assessed in vivo in the lung and liver,
      and in vitro in monocytes from the blood and the lung. Compared with the single 2
      day LPS exposure group, the (2 plus 7 days) repeat LPS-exposed lambs had: 1)
      decreased lung neutrophil and monocyte inducible NO synthase (NOSII) expression,
      and 2) decreased lung cytokine and liver serum amyloid A3 mRNA expression. In the
      lung, serum amyloid A3 mRNA expression decreased in the airway epithelial cells
      but not in the lung inflammatory cells. Unlike the single 7-day LPS exposure
      group, peripheral blood and lung monocytes from the repeat-LPS group did not
      increase IL-6 secretion or hydrogen peroxide production in response to in vitro
      LPS. Compared with controls, TLR4 expression did not change but IL-1R-associated
      kinase M expression increased in the monocytes from repeat LPS-exposed lambs.
      These results are consistent with the novel finding of endotoxin tolerance in
      preterm fetal lungs exposed to intra-amniotic LPS. The findings have implications
      for preterm infants exposed to chorioamnionitis for both responses to lung injury
      and postnatal nosocomial infections.

PMID- 18056397
TI  - Monocyte chemoattractant protein-1/CC chemokine ligand 2 controls microtubule
      driven biogenesis and leukotriene B4-synthesizing function of macrophage lipid
      bodies elicited by innate immune response.
AB  - Lipid bodies (also known as lipid droplets) are emerging as inflammatory
      organelles with roles in the innate immune response to infections and
      inflammatory processes. In this study, we identified MCP-1 as a key endogenous
      mediator of lipid body biogenesis in infection-driven inflammatory disorders and
      we described the cellular mechanisms and signaling pathways involved in the
      ability of MCP-1 to regulate the biogenesis and leukotriene B4 (LTB4) synthetic
      function of lipid bodies. In vivo assays in MCP-1-/- mice revealed that
      endogenous MCP-1 produced during polymicrobial infection or LPS-driven
      inflammatory responses has a critical role on the activation of lipid body
      assembling machinery, as well as on empowering enzymatically these newly formed
      lipid bodies with LTB4 synthetic function within macrophages. MCP-1 triggered
      directly the rapid biogenesis of distinctive LTB4-synthesizing lipid bodies via
      CCR2-driven ERK- and PI3K-dependent intracellular signaling in in vitro
      stimulated macrophages. Disturbance of microtubule organization by microtubule
      active drugs demonstrated that MCP-1-induced lipid body biogenesis also signals
      through a pathway dependent on microtubular dynamics. Besides biogenic process,
      microtubules control LTB4-synthesizing function of MCP-1-elicited lipid bodies,
      in part by regulating the compartmentalization of key proteins, as adipose
      differentiation-related protein and 5-lipoxygenase. Therefore, infection-elicited
      MCP-1, besides its known CCR2-driven chemotactic function, appears as a key
      activator of lipid body biogenic and functional machineries, signaling through a
      microtubule-dependent manner.

PMID- 18056399
TI  - NLRP2, an inhibitor of the NF-kappaB pathway, is transcriptionally activated by
      NF-kappaB and exhibits a nonfunctional allelic variant.
AB  - NLRP2 has been shown to inhibit the NF-kappaB signaling pathway, and thus may
      contribute to modulate the inflammatory response, where NF-kappaB plays a major
      role. In this study, we report that expression of NLRP2 is induced upon
      differentiation of CD34+ hemopoietic progenitors into granulocyte or
      monocyte/macrophages. We also found that NLRP2 was up-regulated following
      differentiation of mesenchymal stem cells toward adipocytes. Notably, stimulation
      of HEK293T cells with TNF-alpha or overexpression of the p65 subunit of NF-kappaB
      resulted in up-regulation of NLRP2 and the formation of NF-kappaB-NLRP2 promoter
      complexes. Moreover, ectopic expression of p65 but not of other transcriptional
      regulators induced transactivation of the NLRP2 promoter. Thus, NLRP2 may control
      NF-kappaB activation through a regulatory loop. Nucleotide changes within the
      NACHT domain of other NLRP proteins have been associated with hereditary fever
      syndromes and chronic inflammatory diseases. We identified five single nucleotide
      polymorphisms present in the NACHT domain of NLRP2 by sequencing genomic DNA from
      319 healthy controls. The frequencies of the rare alleles varied between 0.2 and
      10%. Of note, one of these variants, I352S was unable to block the
      transcriptional activity of NF-kappaB and the formation of NF-kappaB-DNA-binding
      complexes following stimulation with TNF-alpha. Overall, our findings provide
      molecular insight into the expression of NLRP2 by NF-kappaB and suggest that a
      polymorphism within the NACHT domain of NLRP2 may contribute to the amplification
      of inflammatory responses due to a reduction of inhibitory signals on the NF
      kappaB pathway.

PMID- 18056398
TI  - Skin-homing receptors on effector leukocytes are differentially sensitive to
      glyco-metabolic antagonism in allergic contact dermatitis.
AB  - T cell recruitment into inflamed skin is dependent on skin-homing receptor
      binding to endothelial (E)- and platelet (P)-selectin. These T cell receptors, or
      E- and P-selectin ligands, can be targeted by the metabolic fluorosugar
      inhibitor, 4-F-GlcNAc, to blunt cutaneous inflammation. Compelling new data
      indicate that, in addition to T cells, NK cells are also recruited to inflamed
      skin in allergic contact hypersensitivity (CHS) contingent on E- and P-selectin
      binding. Using a model of allergic CHS, we evaluated the identity and impact of
      NK cell E-selectin ligand(s) on inflammatory responses and examined the oral
      efficacy of 4-F-GlcNAc. We demonstrated that the predominant E-selectin ligands
      on NK cells are P-selectin glycoprotein ligand-1 and protease-resistant
      glycolipids. We showed that, unlike the induced E-selectin ligand expression on
      activated T cells upon exposure to Ag, ligand expression on NK cells was
      constitutive. CHS responses were significantly lowered by orally administered 4-F
      GlcNAc treatment. Although E-selectin ligand on activated T cells was suppressed,
      ligand expression on NK cells was insensitive to 4-F-GlcNAc treatment. These
      findings indicate that downregulating effector T cell E- and P-selectin ligand
      expression directly correlates with anti-inflammatory efficacy and provides new
      insight on metabolic discrepancies of E-selectin ligand biosynthesis in effector
      leukocytes in vivo.

PMID- 18056400
TI  - Selective proinflammatory activation of astrocytes by high-mobility group box 1
      protein signaling.
AB  - Extracellular high-mobility group box 1 protein (HMGB1) triggers inflammatory
      events in the brain. We demonstrate that astrocytes, the main glial cells in the
      brain, acquire a specific reactive phenotype when exposed to HMGB1. This cell
      activation, which involves the receptor for advanced glycation end-products and
      the MAPK/ERK1/2 cascade, results in the transcriptional/translational induction
      of a restricted number of inflammatory mediators, including cyclooxygenase-2,
      matrix metalloproteinase-9, and several chemokines of the CC and CXC families.
      The mixture of factors released by HMGB1-reactive astrocytes displays a potent
      chemotactic activity on human monocytic cells. This study is the first to suggest
      that HMGB1/astrocyte interaction plays a specific functional role in the
      progression of inflammatory processes in the CNS by facilitating local leukocyte
      infiltration.

PMID- 18056401
TI  - The required role of endogenously produced lipoxin A4 and annexin-1 for the
      production of IL-10 and inflammatory hyporesponsiveness in mice.
AB  - The appropriate development of an inflammatory response is central for the
      ability of a host to deal with any infectious insult. However, excessive,
      misplaced, or uncontrolled inflammation may lead to acute or chronic diseases.
      The microbiota plays an important role in the control of inflammatory
      responsiveness. In this study, we investigated the role of lipoxin A4 and annexin
      1 for the IL-10-dependent inflammatory hyporesponsiveness observed in germfree
      mice. Administration of a 15-epi-lipoxin A4 analog or an annexin-1-derived
      peptide to conventional mice prevented tissue injury, TNF-alpha production, and
      lethality after intestinal ischemia/reperfusion. This was associated with
      enhanced IL-10 production. Lipoxin A4 and annexin-1 failed to prevent reperfusion
      injury in IL-10-deficient mice. In germfree mice, there was enhanced expression
      of both lipoxin A4 and annexin-1. Blockade of lipoxin A4 synthesis with a 5
      lipoxygenase inhibitor or Abs against annexin-1 partially prevented IL-10
      production and this was accompanied by partial reversion of inflammatory
      hyporesponsiveness in germfree mice. Administration of BOC-1, an antagonist of
      ALX receptors (at which both lipoxin A4 and annexin-1 act), or simultaneous
      administration of 5-lipoxygenase inhibitor and anti-annexin-1 Abs, was associated
      with tissue injury, TNF-alpha production, and lethality similar to that found in
      conventional mice. Thus, our data demonstrate that inflammatory responsiveness is
      tightly controlled by the presence of the microbiota and that the innate capacity
      of germfree mice to produce IL-10 is secondary to their endogenous greater
      ability to produce lipoxin A4 and annexin-1.

PMID- 18056403
TI  - IL-21 induces inhibitor of differentiation 2 and leads to complete abrogation of
      anaphylaxis in mice.
AB  - IL-21 exerts pleiotrophic immunomodulatory activities on a variety of target
      cells including B cells that undergo class switch recombination (CSR) to IgE. In
      this study, we examined whether IgE-mediated systemic anaphylaxis was controlled
      by in vivo administration of IL-21 using the peanut allergy model in mice and
      investigated the molecular mechanisms underlying the IL-21-induced regulation of
      IgE. The anaphylactic reaction was completely abolished by the administration of
      recombinant mouse IL-21 or an IL-21 expression plasmid in terms of the change of
      body temperature and anaphylactic symptoms. The recombinant mouse IL-21 treatment
      remarkably suppressed IgE CSR in splenic B cells, resulting in significant
      decrease in serum concentrations of total as well as allergen-specific IgE. In
      the meanwhile, IL-21 provoked B cells in normal as well as allergic mice to
      express the inhibitor of differentiation 2 (Id2) gene that was shown to be
      crucially involved in the regulation of the activation-induced cytidine deaminase
      and IgE CSR. Moreover, mice genetically deficient for Id2 were completely
      unsusceptible to IL-21-induced prevention of IgE CSR and anaphylaxis. The present
      study strongly suggests that IL-21 is capable of regulating systemic allergic
      reactions by inducing the transcriptional regulator Id2, and the cytokine may be
      useful for clinical intervention for allergic diseases including anaphylaxis.

PMID- 18056402
TI  - Inhibition of neutrophil apoptosis by ATP is mediated by the P2Y11 receptor.
AB  - Neutrophils undergo rapid constitutive apoptosis that is delayed by a range of
      pathogen- and host-derived inflammatory mediators. We have investigated the
      ability of the nucleotide ATP, to which neutrophils are exposed both in the
      circulation and at sites of inflammation, to modulate the lifespan of human
      neutrophils. We found that physiologically relevant concentrations of ATP cause a
      concentration-dependent delay of neutrophil apoptosis (assessed by morphology,
      annexin V/To-Pro3 staining, and mitochondrial membrane permeabilization). We
      found that even brief exposure to ATP (10 min) was sufficient to cause a long
      lasting delay of apoptosis and showed that the effects were not mediated by ATP
      breakdown to adenosine. The P2 receptor mediating the antiapoptotic actions of
      ATP was identified using a combination of more selective ATP analogs, receptor
      expression studies, and study of downstream signaling pathways. Neutrophils were
      shown to express the P2Y11 receptor and inhibition of P2Y11 signaling using the
      antagonist NF157 abrogated the ATP-mediated delay of neutrophil apoptosis, as did
      inhibition of type I cAMP-dependent protein kinases activated downstream of
      P2Y11, without effects on constitutive apoptosis. Specific targeting of P2Y11
      could retain key immune functions of neutrophils but reduce the injurious effects
      of increased neutrophil longevity during inflammation.

PMID- 18056404
TI  - Anti-C5 antibody treatment ameliorates weakness in experimentally acquired
      myasthenia gravis.
AB  - Myasthenia gravis (MG) is a neuromuscular transmission disorder in which damage
      to acetylcholine receptors (AChR) on motor endplates by autoantibody-induced
      complement attack causes muscle weakness. To determine whether and, if so, to
      what extent, blockade of complement cascade at the C5 step ameliorates disease,
      we evaluated the effect of administering a functionally blocking anti-C5 mAb in
      passive experimental MG in Lewis rats induced with AChR Ab McAb-3. In contrast to
      uniform severe weakness at 24 h requiring euthanasia in untreated animals, anti
      C5 mAb-pretreated rats showed no weakness at 48 h. Anti-C5 mAb treatment 24 h
      after disease induction restored strength in two-thirds of the rats.
      Immunofluorescence staining of endplates from the treated animals showed that C9
      deposition at AChR was reduced and ultrastructural analyses showed that endplates
      were intact. The results argue that targeting C5 may warrant testing in MG
      patients and that this approach may be particularly valuable for myasthenic
      crisis.

PMID- 18056405
TI  - Stefan Westermann: a close look at kinetochore function. Interviewed by Caitlin
      Sedwick.
AB  - Stefan Westermann is probing the structure and function of the yeast kinetochore.

PMID- 18056406
TI  - Chromatin modification of Apaf-1 restricts the apoptotic pathway in mature
      neurons.
AB  - Although apoptosis has been extensively studied in developing neurons, the
      dynamic changes in this pathway after neuronal maturation remain largely
      unexplored. We show that as neurons mature, cytochrome c- mediated apoptosis
      progresses from inhibitor of apoptosis protein-dependent to -independent
      regulation because of a complete loss of Apaf-1 expression. However, after DNA
      damage, mature neurons resynthesize Apaf-1 through the cell cycle-related E2F1
      pathway and restore their apoptotic potential. Surprisingly, we find that E2F1 is
      sufficient to induce Apaf-1 expression in developing but not mature neurons.
      Rather, Apaf-1 up-regulation in mature neurons requires both chromatin
      derepression and E2F1 transcriptional activity. This differential capacity of
      E2F1 to induce Apaf-1 transcription is because of the association of the Apaf-1
      promoter with active chromatin in developing neurons and repressed chromatin in
      mature neurons. These data specifically illustrate how the apoptotic pathway in
      mature neurons becomes increasingly restricted by a novel mechanism involving the
      regulation of chromatin structure.

PMID- 18056407
TI  - Lack of TRF2 in ALT cells causes PML-dependent p53 activation and loss of
      telomeric DNA.
AB  - Alternative lengthening of telomere (ALT) tumors maintain telomeres by a
      telomerase-independent mechanism and are characterized by a nuclear structure
      called the ALT-associated PML body (APB). TRF2 is a component of a telomeric
      DNA/protein complex called shelterin. However, TRF2 function in ALT cells remains
      elusive. In telomerase-positive tumor cells, TRF2 inactivation results in
      telomere de-protection, activation of ATM, and consequent induction of p53
      dependent apoptosis. We show that in ALT cells this sequence of events is
      different. First, TRF2 inactivation/silencing does not induce cell death in p53
      proficient ALT cells, but rather triggers cellular senescence. Second, ATM is
      constitutively activated in ALT cells and colocalizes with TRF2 into APBs.
      However, it is only following TRF2 silencing that the ATM target p53 is
      activated. In this context, PML is indispensable for p53-dependent p21 induction.
      Finally, we find a substantial loss of telomeric DNA upon stable TRF2 knockdown
      in ALT cells. Overall, we provide insight into the functional consequences of
      shelterin alterations in ALT cells.

PMID- 18056408
TI  - Endoplasmic reticulum remains continuous and undergoes sheet-to-tubule
      transformation during cell division in mammalian cells.
AB  - The endoplasmic reticulum (ER) is a multifaceted cellular organelle both
      structurally and functionally, and its cell cycle-dependent morphological changes
      are poorly understood. Our quantitative confocal and EM analyses show that the ER
      undergoes dramatic reorganization during cell division in cultured mammalian
      cells as mitotic ER profiles become shorter and more branched. 3D modeling by
      electron tomography reveals that the abundant interphase structures, sheets, are
      lost and subsequently transform into a branched tubular network that remains
      continuous. This is confirmed by observing the most prominent ER subdomain, the
      nuclear envelope (NE). A NE marker protein spreads to the mitotic ER tubules,
      although it does not show a homogenous distribution within the network. We
      mimicked the mitotic ER reorganization using puromycin to strip the membrane
      bound ribosomes from the interphase ER corresponding to the observed loss of
      ribosomes normally occurring during mitosis. We propose that the structural
      changes in mitotic ER are linked to ribosomal action on the ER membranes.

PMID- 18056409
TI  - Megf10 regulates the progression of the satellite cell myogenic program.
AB  - We identify here the multiple epidermal growth factor repeat transmembrane
      protein Megf10 as a quiescent satellite cell marker that is also expressed in
      skeletal myoblasts but not in differentiated myofibers. Retroviral expression of
      Megf10 in myoblasts results in enhanced proliferation and inhibited
      differentiation. Infected myoblasts that fail to differentiate undergo cell cycle
      arrest and can reenter the cell cycle upon serum restimulation. Moreover,
      experimental modulations of Megf10 alter the expression levels of Pax7 and the
      myogenic regulatory factors. In contrast, Megf10 silencing in activated satellite
      cells on individual fibers or in cultured myoblasts results in a dramatic
      reduction in the cell number, caused by myogenin activation and precocious
      differentiation as well as a depletion of the self-renewing Pax7+/MyoD-
      population. Additionally, Megf10 silencing in MyoD-/- myoblasts results in down
      regulation of Notch signaling components. We conclude that Megf10 represents a
      novel transmembrane protein that impinges on Notch signaling to regulate the
      satellite cell population balance between proliferation and differentiation.

PMID- 18056410
TI  - A function for tyrosine phosphorylation of type 1 inositol 1,4,5-trisphosphate
      receptor in lymphocyte activation.
AB  - Sustained elevation of intracellular calcium by Ca2+ release-activated Ca2+
      channels is required for lymphocyte activation. Sustained Ca2+ entry requires
      endoplasmic reticulum (ER) Ca2+ depletion and prolonged activation of inositol
      1,4,5-trisphosphate receptor (IP(3)R)/Ca2+ release channels. However, a major
      isoform in lymphocyte ER, IP3R1, is inhibited by elevated levels of cytosolic
      Ca2+, and the mechanism that enables the prolonged activation of IP(3)R1 required
      for lymphocyte activation is unclear. We show that IP(3)R1 binds to the
      scaffolding protein linker of activated T cells and colocalizes with the T cell
      receptor during activation, resulting in persistent phosphorylation of IP(3)R1 at
      Tyr353. This phosphorylation increases the sensitivity of the channel to
      activation by IP(3) and renders the channel less sensitive to Ca2+ -induced
      inactivation. Expression of a mutant IP3R1-Y353F channel in lymphocytes causes
      defective Ca2+ signaling and decreased nuclear factor of activated T cells
      activation. Thus, tyrosine phosphorylation of IP3R1-Y353 may have an important
      function in maintaining elevated cytosolic Ca2+ levels during lymphocyte
      activation.

PMID- 18056411
TI  - Site-specific ubiquitination exposes a linear motif to promote interferon-alpha
      receptor endocytosis.
AB  - Ligand-induced endocytosis and lysosomal degradation of cognate receptors
      regulate the extent of cell signaling. Along with linear endocytic motifs that
      recruit the adaptin protein complex 2 (AP2)-clathrin molecules,
      monoubiquitination of receptors has emerged as a major endocytic signal. By
      investigating ubiquitin-dependent lysosomal degradation of the interferon (IFN)
      alpha/beta receptor 1 (IFNAR1) subunit of the type I IFN receptor, we reveal that
      IFNAR1 is polyubiquitinated via both Lys48- and Lys63-linked chains. The
      SCF(betaTrcp) (Skp1-Cullin1-F-box complex) E3 ubiquitin ligase that mediates
      IFNAR1 ubiquitination and degradation in cells can conjugate both types of chains
      in vitro. Although either polyubiquitin linkage suffices for postinternalization
      sorting, both types of chains are necessary but not sufficient for robust IFNAR1
      turnover and internalization. These processes also depend on the proximity of
      ubiquitin-acceptor lysines to a linear endocytic motif and on its integrity.
      Furthermore, ubiquitination of IFNAR1 promotes its interaction with the AP2
      adaptin complex that is required for the robust internalization of IFNAR1,
      implicating cooperation between site-specific ubiquitination and the linear
      endocytic motif in regulating this process.

PMID- 18056412
TI  - Biogenesis of gamma-secretase early in the secretory pathway.
AB  - Gamma-Secretase is responsible for proteolytic maturation of signaling and cell
      surface proteins, including amyloid precursor protein (APP). Abnormal processing
      of APP by gamma-secretase produces a fragment, Abeta(42), that may be responsible
      for Alzheimer's disease (AD). The biogenesis and trafficking of this important
      enzyme in relation to aberrant Abeta processing is not well defined. Using a cell
      free reaction to monitor the exit of cargo proteins from the endoplasmic
      reticulum (ER), we have isolated a transient intermediate of gamma-secretase.
      Here, we provide direct evidence that the gamma-secretase complex is formed in an
      inactive complex at or before the assembly of an ER transport vesicle dependent
      on the COPII sorting subunit, Sec24A. Maturation of the holoenzyme is achieved in
      a subsequent compartment. Two familial AD (FAD)-linked PS1 variants are
      inefficiently packaged into transport vesicles generated from the ER. Our results
      suggest that aberrant trafficking of PS1 may contribute to disease pathology.

PMID- 18056413
TI  - Requirements for sulfate transport and the diastrophic dysplasia sulfate
      transporter in fibronectin matrix assembly.
AB  - Diastrophic dysplasia sulfate transporter (DTDST) is a sulfate/chloride
      antiporter whose function is impaired in several human chondrodysplasias. We show
      that DTDST is upregulated by dexamethasone stimulation of HT1080 fibrosarcoma
      cells and is required for fibronectin (FN) extracellular matrix deposition by
      these cells. DTDST imports sulfate for the modification of glycosaminoglycans. We
      find that N-sulfation of these chains is important for FN matrix assembly and
      that sulfation of cell surface proteoglycans is reduced in the absence of DTDST.
      Of the candidate HT1080 cell surface proteoglycans, only loss of syndecan-2
      compromises FN assembly, as shown by syndecan-2 small interfering RNA knockdown.
      DTDST is both necessary and sufficient to induce FN matrix assembly in HT1080
      cells. Knockdown of DTDST ablates FN matrix, whereas its overexpression increases
      assembly without dexamethasone stimulation. These results identify a previously
      unrecognized regulatory pathway for matrix assembly via modulation of a sulfate
      transporter and proteoglycan sulfation. These data raise the possibility that FN
      assembly defects contribute to chondrodysplasias.

PMID- 18056414
TI  - Structural basis of filamin A functions.
AB  - Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many
      cellular constituents. FLNa dimeric subunits have N-terminal spectrin family F
      actin binding domains (ABDs) and an elongated flexible segment of 24
      immunoglobulin (Ig) repeats. We generated a library of FLNa fragments to examine
      their F-actin binding to define the structural properties of FLNa that enable its
      various functions. We find that Ig repeats 9-15 contain an F-actin-binding domain
      necessary for high avidity F-actin binding. Ig repeats 16-24, where most FLNa
      binding partners interact, do not bind F-actin, and thus F-actin does not compete
      with Ig repeat 23 ligand, FilGAP. Ig repeats 16-24 have a compact structure that
      suggests their unfolding may accommodate pre-stress-mediated stiffening of F
      actin networks, partner binding, mechanosensing, and mechanoprotection properties
      of FLNa. Our results also establish the orientation of FLNa dimers in F-actin
      branching. Dimerization, mediated by FLNa Ig repeat 24, accounts for rigid high
      angle FLNa/F-actin branching resistant to bending by thermal forces, and high
      avidity F-actin binding and cross-linking.

PMID- 18056416
TI  - Vinculin controls focal adhesion formation by direct interactions with talin and
      actin.
AB  - Focal adhesions (FAs) regulate cell migration. Vinculin, with its many potential
      binding partners, can interconnect signals in FAs. Despite the well-characterized
      structure of vinculin, the molecular mechanisms underlying its action have
      remained unclear. Here, using vinculin mutants, we separate the vinculin head and
      tail regions into distinct functional domains. We show that the vinculin head
      regulates integrin dynamics and clustering and the tail regulates the link to the
      mechanotransduction force machinery. The expression of vinculin constructs with
      unmasked binding sites in the head and tail regions induces dramatic FA growth,
      which is mediated by their direct interaction with talin. This interaction leads
      to clustering of activated integrin and an increase in integrin residency time in
      FAs. Surprisingly, paxillin recruitment, induced by active vinculin constructs,
      occurs independently of its potential binding site in the vinculin tail. The
      vinculin tail, however, is responsible for the functional link of FAs to the
      actin cytoskeleton. We propose a new model that explains how vinculin
      orchestrates FAs.

PMID- 18056415
TI  - Dual roles of myocardin-related transcription factors in epithelial mesenchymal
      transition via slug induction and actin remodeling.
AB  - Epithelial-mesenchymal transition (EMT) is a critical process occurring during
      embryonic development and in fibrosis and tumor progression. Dissociation of cell
      cell contacts and remodeling of the actin cytoskeleton are major events of the
      EMT. Here, we show that myocardin-related transcription factors (MRTFs; also
      known as MAL and MKL) are critical mediators of transforming growth factor beta
      (TGF-beta) 1-induced EMT. In all epithelial cell lines examined here, TGF-beta1
      triggers the nuclear translocation of MRTFs. Ectopic expression of constitutive
      active MRTF-A induces EMT, whereas dominant-negative MRTF-A or knockdown of MRTF
      A and -B prevents the TGF-beta1-induced EMT. MRTFs form complexes with Smad3. Via
      Smad3, the MRTF-Smad3 complexes bind to a newly identified cis-element GCCG-like
      motif in the promoter region of Canis familiaris and the human slug gene, which
      activates slug transcription and thereby dissociation of cell-cell contacts.
      MRTFs also increase the expression levels of actin cytoskeletal proteins via
      serum response factor, thereby triggering reorganization of the actin
      cytoskeleton. Thus, MRTFs are important mediators of TGF-beta1-induced EMT.

PMID- 18056417
TI  - Monomer dimer dynamics and distribution of GPI-anchored uPAR are determined by
      cell surface protein assemblies.
AB  - To search for functional links between glycosylphosphatidylinositol (GPI) protein
      monomer-oligomer exchange and membrane dynamics and confinement, we studied
      urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in
      the regulation of cell adhesion, migration, and proliferation. Using a
      functionally active fluorescent protein-uPAR in live cells, we analyzed the
      effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics
      and dimerization at the cell membrane. Vitronectin directs the recruitment of
      dimers and slows down the diffusion of the receptors at the basal membrane. The
      commitment to uPA-plasminogen activator inhibitor type 1-mediated endocytosis and
      recycling modifies uPAR diffusion and induces an exchange between uPAR monomers
      and dimers. This exchange is fully reversible. The data demonstrate that cell
      surface protein assemblies are important in regulating the dynamics and
      localization of uPAR at the cell membrane and the exchange of monomers and
      dimers. These results also provide a strong rationale for dynamic studies of GPI
      anchored molecules in live cells at steady state and in the absence of cross
      linker/clustering agents.

PMID- 18056418
TI  - RecQ helicases queuing with Srs2 to disrupt Rad51 filaments and suppress
      recombination.

PMID- 18056419
TI  - Dynamics and interplay of nuclear architecture, genome organization, and gene
      expression.
AB  - The organization of the genome in the nucleus of a eukaryotic cell is fairly
      complex and dynamic. Various features of the nuclear architecture, including
      compartmentalization of molecular machines and the spatial arrangement of genomic
      sequences, help to carry out and regulate nuclear processes, such as DNA
      replication, DNA repair, gene transcription, RNA processing, and mRNA transport.
      Compartmentalized multiprotein complexes undergo extensive modifications or
      exchange of protein subunits, allowing for an exquisite dynamics of structural
      components and functional processes of the nucleus. The architecture of the
      interphase nucleus is linked to the spatial arrangement of genes and gene
      clusters, the structure of chromatin, and the accessibility of regulatory DNA
      elements. In this review, we discuss recent studies that have provided exciting
      insight into the interplay between nuclear architecture, genome organization, and
      gene expression.

PMID- 18056420
TI  - The hematopoietic stem cell and its niche: a comparative view.
AB  - Stem cells have been identified as a source of virtually all highly
      differentiated cells that are replenished during the lifetime of an animal. The
      critical balance between stem and differentiated cell populations is crucial for
      the long-term maintenance of functional tissue types. Stem cells maintain this
      balance by choosing one of several alternate fates: self-renewal, commitment to
      differentiate, and senescence or cell death. These characteristics comprise the
      core criteria by which these cells are usually defined. The self-renewal property
      is important, as it allows for extended production of the corresponding
      differentiated cells throughout the life span of the animal. A microenvironment
      that is supportive of stem cells is commonly referred to as a stem cell niche. In
      this review, we first present some general concepts regarding stem cells and
      their niches, comparing stem cells of many different kinds from diverse
      organisms, and in the second part, we compare specific aspects of hematopoiesis
      and the niches that support hematopoiesis in Drosophila, zebrafish and mouse.

PMID- 18056421
TI  - Atg7-dependent autophagy promotes neuronal health, stress tolerance, and
      longevity but is dispensable for metamorphosis in Drosophila.
AB  - Autophagy, a cellular process of cytoplasmic degradation and recycling, is
      induced in Drosophila larval tissues during metamorphosis, potentially
      contributing to their destruction or reorganization. Unexpectedly, we find that
      flies lacking the core autophagy regulator Atg7 are viable, despite severe
      defects in autophagy. Although metamorphic cell death is perturbed in Atg7
      mutants, the larval-adult midgut transition proceeds normally, with extended
      pupal development compensating for reduced autophagy. Atg7-/- adults are short
      lived, hypersensitive to nutrient and oxidative stress, and accumulate ubiquitin
      positive aggregates in degenerating neurons. Thus, normal levels of autophagy are
      crucial for stress survival and continuous cellular renewal, but not
      metamorphosis.

PMID- 18056422
TI  - Human Y5 RNA specializes a Ro ribonucleoprotein for 5S ribosomal RNA quality
      control.
AB  - Humans express four distinct non-protein-coding Y RNAs (ncRNAs). To investigate Y
      RNA functional diversification, we exploited an RNA-based affinity purification
      method to isolate ribonucleoproteins (RNPs) assembled on individual human Y RNAs.
      Silver staining and mass spectrometry revealed that the Ro and La proteins
      assemble with all Y RNAs, while additional proteins associate with specific Y
      RNAs. Unexpectedly, Y5 RNA uniquely copurified ribosomal protein L5 and its
      binding partner 5S RNA. These findings reveal a contribution of Y5 to 5S
      surveillance and suggest that interactions between Ro-Y5 and L5-5S RNPs establish
      5S RNA as a target of quality control.

PMID- 18056423
TI  - Hepatic IGFBP1 is a prosurvival factor that binds to BAK, protects the liver from
      apoptosis, and antagonizes the proapoptotic actions of p53 at mitochondria.
AB  - Liver is generally refractory to apoptosis induced by the p53 tumor suppressor
      protein, but the molecular basis remains poorly understood. Here we show that p53
      transcriptional activation leads to enhanced expression of hepatic IGFBP1
      (insulin-like growth factor-binding protein-1). Exhibiting a previously
      unanticipated role, a portion of intracellular IGFBP1 protein localizes to
      mitochondria where it binds to the proapoptotic protein BAK and hinders BAK
      activation and apoptosis induction. Interestingly, in many cells and tissues p53
      also has a direct apoptotic function at mitochondria that includes BAK binding
      and activation. When IGFBP1 is in a complex with BAK, formation of a proapoptotic
      p53/BAK complex and apoptosis induction are impaired, both in cultured cells and
      in liver. In contrast, livers of IGFBP1-deficient mice exhibit spontaneous
      apoptosis that is accompanied by p53 mitochondrial accumulation and evidence of
      BAK oligomerization. These data support the importance of BAK as a mediator of
      p53's mitochondrial function. The results also identify IGFBP1 as a negative
      regulator of the BAK-dependent pathway of apoptosis, whose expression integrates
      the transcriptional and mitochondrial functions of the p53 tumor suppressor
      protein.

PMID- 18056424
TI  - Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and
      transcriptional silencing.
AB  - Increased methylation of CpG islands and silencing of affected target genes is
      frequently found in human cancer; however, in vivo the question of causality has
      only been addressed by loss-of-function studies. To directly evaluate the role
      and mechanism of de novo methylation in tumor development, we overexpressed the
      de novo DNA methyltransferases Dnmt3a1 and Dnmt3b1 in Apc Min/+ mice. We found
      that Dnmt3b1 enhanced the number of colon tumors in Apc Min/+ mice approximately
      twofold and increased the average size of colonic microadenomas, whereas Dnmt3a1
      had no effect. The overexpression of Dnmt3b1 caused loss of imprinting and
      increased expression of Igf2 as well as methylation and transcriptional silencing
      of the tumor suppressor genes Sfrp2, Sfrp4, and Sfrp5. Importantly, we found that
      Dnmt3b1 but not Dnmt3a1 efficiently methylates the same set of genes in tumors
      and in nontumor tissues, demonstrating that de novo methyltransferases can
      initiate methylation and silencing of specific genes in phenotypically normal
      cells. This suggests that DNA methylation patterns in cancer are the result of
      specific targeting of at least some tumor suppressor genes rather than of random,
      stochastic methylation followed by clonal selection due to a proliferative
      advantage caused by tumor suppressor gene silencing.

PMID- 18056425
TI  - Mechanism of mRNA deadenylation: evidence for a molecular interplay between
      translation termination factor eRF3 and mRNA deadenylases.
AB  - In eukaryotes, shortening of the 3'-poly(A) tail is the rate-limiting step in the
      degradation of most mRNAs, and two major mRNA deadenylase complexes--Caf1-Ccr4
      and Pan2-Pan3--play central roles in this process, referred to as deadenylation.
      However, the molecular mechanism triggering deadenylation remains elusive.
      Previously, we demonstrated that eukaryotic releasing factor eRF3 mediates
      deadenylation and decay of mRNA in a manner coupled to translation termination.
      Here, we report the mechanism of mRNA deadenylation. The eRF3-mediated
      deadenylation is catalyzed by both Caf1-Ccr4 and Pan2-Pan3. Interestingly,
      translation termination complexes eRF1-eRF3, Pan2-Pan3, and Caf1-Ccr4
      competitively interact with polyadenylate-binding protein PABPC1. In each
      complex, eRF3, Pan3, and Tob, respectively, mediate PABPC1 binding, and a
      combination of a PAM2 motif and a PABC domain is commonly utilized for their
      contacts. A translation-dependent exchange of eRF1-eRF3 for the deadenylase
      occurs on PABPC1. Consequently, PABPC1 binding leads to the activation of Pan2
      Pan3 and Caf1-Ccr4. From these results, we suggest a mechanism of mRNA
      deadenylation by Pan2-Pan3 and Caf1-Ccr4 in cooperation with eRF3 and PABPC1.

PMID- 18056426
TI  - The mechanism of an exceptional case of reinitiation after translation of a long
      ORF reveals why such events do not generally occur in mammalian mRNA translation.
AB  - The subgenomic mRNA of feline caliciviruses is bicistronic with the two cistrons
      overlapping by four nucleotides, ..AUGA. The upstream cistron encodes a 75-kDa
      major capsid protein precursor (pre-VP1), and the downstream cistron a 10-kDa
      minor capsid protein. The kinetics of translation in reticulocyte lysates show
      that the downstream cistron is translated by a termination-reinitiation process,
      which is unusual in not requiring eIF4G or the eIF4F complex. Reinitiation
      requires the 3'-terminal 87 nucleotides (nt) of the pre-VP1 ORF, but no other
      viral sequences. The reinitiation site is selected by virtue of its proximity to
      this 87-nt element, and not its proximity to the pre-VP1 ORF stop codon, although
      this must be located not more than approximately 30 nt downstream from the
      restart codon. This 87-nt element was shown to bind 40S ribosomal subunits and
      initiation factor eIF3, and addition of supplementary eIF3 enhanced reinitiation
      efficiency. Mutants defective in reinitiation showed reduced affinity for eIF3 or
      defective 40S subunit binding (or both). These results suggest a mechanism in
      which some of the eIF3/40S complexes formed during disassembly of post
      termination ribosomes bind to this 87-nt element in a position appropriate for
      reinitiation following acquisition of an eIF2/GTP/Met-tRNA i ternary complex.

PMID- 18056427
TI  - Genome-wide view of cell fate specification: ladybird acts at multiple levels
      during diversification of muscle and heart precursors.
AB  - Correct diversification of cell types during development ensures the formation of
      functional organs. The evolutionarily conserved homeobox genes from ladybird/Lbx
      family were found to act as cell identity genes in a number of embryonic tissues.
      A prior genetic analysis showed that during Drosophila muscle and heart
      development ladybird is required for the specification of a subset of muscular
      and cardiac precursors. To learn how ladybird genes exert their cell identity
      functions we performed muscle and heart-targeted genome-wide transcriptional
      profiling and a chromatin immunoprecipitation (ChIP)-on-chip search for direct
      Ladybird targets. Our data reveal that ladybird not only contributes to the
      combinatorial code of transcription factors specifying the identity of muscle and
      cardiac precursors, but also regulates a large number of genes involved in
      setting cell shape, adhesion, and motility. Among direct ladybird targets, we
      identified bric-a-brac 2 gene as a new component of identity code and inflated
      encoding alphaPS2-integrin playing a pivotal role in cell-cell interactions.
      Unexpectedly, ladybird also contributes to the regulation of terminal
      differentiation genes encoding structural muscle proteins or contributing to
      muscle contractility. Thus, the identity gene-governed diversification of cell
      types is a multistep process involving the transcriptional control of genes
      determining both morphological and functional properties of cells.

PMID- 18056428
TI  - The C. elegans protein CEH-30 protects male-specific neurons from apoptosis
      independently of the Bcl-2 homolog CED-9.
AB  - The developmental control of apoptosis is fundamental and important. We report
      that the Caenorhabditis elegans Bar homeodomain transcription factor CEH-30 is
      required for the sexually dimorphic survival of the male-specific CEM (cephalic
      male) sensory neurons; the homologous cells of hermaphrodites undergo programmed
      cell death. We propose that the cell-type-specific anti-apoptotic gene ceh-30 is
      transcriptionally repressed by the TRA-1 transcription factor, the terminal
      regulator of sexual identity in C. elegans, to cause hermaphrodite-specific CEM
      death. The established mechanism for the regulation of specific programmed cell
      deaths in C. elegans is the transcriptional control of the BH3-only gene egl-1,
      which inhibits the Bcl-2 homolog ced-9; similarly, most regulation of vertebrate
      apoptosis involves the Bcl-2 superfamily. In contrast, ceh-30 acts within the CEM
      neurons to promote their survival independently of both egl-1 and ced-9.
      Mammalian ceh-30 homologs can substitute for ceh-30 in C. elegans. Mice lacking
      the ceh-30 homolog Barhl1 show a progressive loss of sensory neurons and
      increased sensory-neuron cell death. Based on these observations, we suggest that
      the function of Bar homeodomain proteins as cell-type-specific inhibitors of
      apoptosis is evolutionarily conserved.

PMID- 18056429
TI  - Control of sex-specific apoptosis in C. elegans by the BarH homeodomain protein
      CEH-30 and the transcriptional repressor UNC-37/Groucho.
AB  - Apoptosis is essential for proper development and tissue homeostasis in
      metazoans. It plays a critical role in generating sexual dimorphism by
      eliminating structures that are not needed in a specific sex. The molecular
      mechanisms that regulate sexually dimorphic apoptosis are poorly understood. Here
      we report the identification of the ceh-30 gene as a key regulator of sex
      specific apoptosis in Caenorhabditis elegans. Loss-of-function mutations in ceh
      30 cause the ectopic death of male-specific CEM neurons. ceh-30 encodes a BarH
      homeodomain protein that acts downstream from the terminal sex determination gene
      tra-1, but upstream of, or in parallel to, the cell-death-initiating gene egl-1
      to protect CEM neurons from undergoing apoptosis in males. The second intron of
      the ceh-30 gene contains two adjacent cis-elements that are binding sites for TRA
      1A and a POU-type homeodomain protein UNC-86 and acts as a sensor to regulate
      proper specification of the CEM cell fate. Surprisingly, the N terminus of CEH-30
      but not its homeodomain is critical for CEH-30's cell death inhibitory activity
      in CEMs and contains a conserved eh1/FIL domain that is important for the
      recruitment of the general transcriptional repressor UNC-37/Groucho. Our study
      suggests that ceh-30 defines a critical checkpoint that integrates the sex
      determination signal TRA-1 and the cell fate determination and survival signal
      UNC-86 to control the sex-specific activation of the cell death program in CEMs
      through the general transcription repressor UNC-37.

PMID- 18056430
TI  - Nuclear factor-kappaB, an unappreciated tumor suppressor.
AB  - The notion that nuclear factor-kappaB (NF-kappaB) is a tumor-promoting
      transcription factor has become a widely accepted dogma in biology. However,
      recent findings suggest an inhibitory role for NF-kappaB in carcinogenesis and
      tumorigenesis. Although the tumor suppressor-like effect of NF-kappaB remains to
      be rigorously established by further studies using cellular and animal models,
      these latest findings warrant caution with respect to blockage of NF-kappaB
      activation as a broad strategy in treating cancers.

PMID- 18056431
TI  - The guardian's little helper: microRNAs in the p53 tumor suppressor network.
AB  - Several microRNAs (miRNAs) have been implicated in tumor development based on
      both changes in their expression patterns and gene structural alterations in
      human tumors. However, we are only now beginning to see how miRNAs interact with
      classic oncogene and tumor suppressor mechanisms. Several recent studies have
      implicated the miR-34 family of miRNAs in the p53 tumor suppressor network. The
      expression of miR-34a, miR-34b, and miR-34c is robustly induced by DNA damage and
      oncogenic stress in a p53-dependent manner. When overexpressed, miR-34 leads to
      apoptosis or cellular senescence, whereas reduction of miR-34 function attenuates
      p53-mediated cell death. These findings, together with the fact that miR-34 is
      down-regulated in several types of human cancer, show that miRNAs can affect
      tumorigenesis by working within the confines of well-known tumor suppressor
      pathways.

PMID- 18056432
TI  - Polo-like kinase 1 is involved in invasion through extracellular matrix.
AB  - Polo-like kinase 1 (PLK1) has important functions in maintaining genome stability
      via its role in mitosis. Because PLK1 is up-regulated in many invasive
      carcinomas, we asked whether it may also play a role in acquisition of
      invasiveness, a crucial step in transition to malignancy. In a model of
      metaplastic basal-like breast carcinoma progression, we found that PLK1
      expression is necessary but not sufficient to induce invasiveness through laminin
      rich extracellular matrix. PLK1 mediates invasion via vimentin and beta1
      integrin, both of which are necessary. We observed that PLK1 phosphorylates
      vimentin on Ser82, which in turn regulates cell surface levels of beta1 integrin.
      We found PLK1 to be also highly expressed in preinvasive in situ carcinomas of
      the breast. These results support a role for the involvement of PLK1 in the
      invasion process and point to this pathway as a potential therapeutic target for
      preinvasive and invasive breast carcinoma treatment.

PMID- 18056433
TI  - MicroRNAs as potential agents to alter resistance to cytotoxic anticancer
      therapy.
AB  - Tumor cells use preexisting prosurvival signaling pathways to evade the damaging
      and cytotoxic effects of anticancer agents. Radiation therapy is a primary form
      of cytotoxic anticancer treatment, but agents that successfully modify the
      radiation response in vivo are lacking. MicroRNAs (miRNA) are global gene
      regulators that play critical roles in oncogenesis and have been found to
      regulate prosurvival pathways. However, there is little understanding of how
      cellular miRNA expression affects the response of a cancer to cytotoxic therapy
      and ultimately outcome. The let-7 family of miRNAs regulates expression of
      oncogenes, such as RAS, and is specifically down-regulated in many cancer
      subtypes. In fact, low levels of let-7 predict a poor outcome in lung cancer.
      Here, we report that the let-7 family of miRNAs is overrepresented in a class of
      miRNAs exhibiting altered expression in response to radiation. More strikingly,
      we also can create a radiosensitive state when the select let-7 family of miRNAs
      is overexpressed in vitro in lung cancer cells and in vivo in a Caenorhabditis
      elegans model of radiation-induced cell death, whereas decreasing their levels
      causes radioresistance. In C. elegans, we show that this is partly through
      control of the proto-oncogene homologue let-60/RAS and genes in the DNA damage
      response pathway. These findings are the first direct evidence that miRNAs can
      suppress resistance to anticancer cytotoxic therapy, a common feature of cancer
      cells, and suggest that miRNAs may be a viable tool to augment current cancer
      therapies.

PMID- 18056434
TI  - Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of
      formaldehyde.
AB  - Formaldehyde is an aliphatic monoaldehyde and is a highly reactive environmental
      human carcinogen. Whereas humans are continuously exposed to exogenous
      formaldehyde, this reactive aldehyde is a naturally occurring biological compound
      that is present in human plasma at concentrations ranging from 13 to 97
      micromol/L. It has been well documented that DNA-protein crosslinks (DPC) likely
      play an important role with regard to the genotoxicity and carcinogenicity of
      formaldehyde. However, little is known about which DNA damage response pathways
      are essential for cells to counteract formaldehyde. In the present study, we
      first assessed the DNA damage response to plasma levels of formaldehyde using
      chicken DT40 cells with targeted mutations in various DNA repair genes. Here, we
      show that the hypersensitivity to formaldehyde is detected in DT40 mutants
      deficient in the BRCA/FANC pathway, homologous recombination, or translesion DNA
      synthesis. In addition, FANCD2-deficient DT40 cells are hypersensitive to
      acetaldehyde, but not to acrolein, crotonaldehyde, glyoxal, and methylglyoxal.
      Human cells deficient in FANCC and FANCG are also hypersensitive to plasma levels
      of formaldehyde. These results indicate that the BRCA/FANC pathway is essential
      to counteract DPCs caused by aliphatic monoaldehydes. Based on the results
      obtained in the present study, we are currently proposing that endogenous
      formaldehyde might have an effect on highly proliferating cells, such as bone
      marrow cells, as well as an etiology of cancer in Fanconi anemia patients.

PMID- 18056435
TI  - Plasma cysteinylglycine levels and breast cancer risk in women.
AB  - Cysteinylglycine, a prooxidant generated during the catabolism of glutathione,
      has been suggested to induce oxidative stress and lipid peroxidation, leading to
      the development of human cancers. Observational data relating cysteinylglycine
      status to breast cancer risk are lacking. We prospectively evaluated plasma
      cysteinylglycine levels and invasive breast cancer risk among 812 case-control
      pairs nested in the Women's Health Study, a completed randomized trial evaluating
      low-dose aspirin and vitamin E in middle-aged and older women. We additionally
      evaluated the effect modification by risk factors for oxidative stress, such as
      vitamin E assignment, alcohol consumption, obesity, and postmenopausal hormone
      use. Logistic regression controlling for matching factors, as well as other risk
      factors for breast cancer, was used to estimate relative risks (RR) and 95%
      confidence intervals (95% CI). All statistical tests were two sided. We observed
      no overall association between plasma cysteinylglycine and invasive breast cancer
      risk. However, higher cysteinylglycine levels were marginally associated with an
      increased risk of breast cancer in the high oxidative stress groups. Women in the
      highest quintile group of cysteinylglycine relative to the lowest group had
      multivariate RRs (95% CIs) of 1.64 (1.01-2.66; P(trend) = 0.04) in the vitamin E
      placebo group, 2.51 (1.01-6.24; P(trend) = 0.07) in the high alcohol intake group
      (>or=9 g/day), and 1.66 (0.97-2.84; P(trend) = 0.03) in the overweight and obese
      group. Our findings suggest that women who are susceptible to experiencing
      oxidative stress may be at a greater risk for developing breast cancer.

PMID- 18056436
TI  - Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: results
      from the Colon Cancer Family Registry.
AB  - Recent publications have reported that common variants on 8q24 are associated
      with both prostate and colorectal cancers (CRC). In addition, one of these
      studies (the ARCTIC study) initially observed an association with a single
      nucleotide polymorphism (SNP) on 9p24 that was not confirmed in some of their
      validation data sets. In the research described here, we conducted a case
      unaffected sibling analysis using population- and clinic-based discordant
      sibships (N = 1,567 sibships) from the Colon Cancer Family Registry (Colon CFR)
      to investigate the associations between common variants at 9p24 and 8q24 and risk
      of CRC. We also evaluated whether these associations differed by age, family
      history, and tumor characteristics, including microsatellite instability and
      tumor site. Associations were estimated using conditional logistic regression,
      treating sibship as the matching factor. Analyses were adjusted for age and sex,
      and stratified by ascertainment source (population versus clinic). We observed an
      association between a SNP on 9p24 (rs719725) and risk of CRC in the population
      based series (AA versus CC: odds ratios, 1.46; 95% confidence interval, 1.06
      2.02; AC versus CC: odds ratios, 1.50; 95% confidence interval, 1.14-1.98; P =
      0.011 on 2 df). In the population-based series, we also detected statistically
      significant associations between two SNPs on 8q24, rs10505477 and rs6983267, and
      risk of CRC (P = 0.005 and P = 0.002, respectively). There was no evidence of
      statistically significant heterogeneity by age at diagnosis, family history of
      CRC, microsatellite instability, or tumor site at either locus and no evidence of
      interaction between SNPs on 8q24 and 9p24. These data suggest that common
      variants may play important roles in the risk of CRC.

PMID- 18056437
TI  - Direct transcriptional activation of promyelocytic leukemia protein by IFN
      regulatory factor 3 induces the p53-dependent growth inhibition of cancer cells.
AB  - IFN regulatory factor 3 (IRF3) is a transcriptional factor that plays a crucial
      role in activation of innate immunity and inflammation in response to viral
      infection, and is also involved in p53-dependent inhibition of cell growth.
      Although functional activation of IRF3 by viral infection is relatively well
      documented, the biological role and regulatory mechanism underlying cell growth
      inhibition by IRF3 are poorly understood. Here, we show a novel regulatory
      pathway connecting IRF3-promyelocytic leukemia protein (PML)-p53 in primary and
      cancer cell lines. Overexpression of IRF3 induces p53-dependent cell growth
      inhibition in cancer cell lines with normal p53 activity. In addition,
      doxycycline-induced expression of IRF3 in U87MG cells inhibits tumor growth in
      nude mice in vivo. IRF3 is found to increase expression of PML by a direct
      transcriptional activation as determined by PML-promoter-luciferase and chromatin
      immunoprecipitation assays. When PML is depleted by RNA interference-mediated
      knockdown, IRF3 fails to increase p53 acetylation and its transcriptional
      activity. Taken together, the results of the present study indicate that direct
      transcriptional activation of PML by IRF3 results in the p53-dependent growth
      inhibition of normal and cancer cells in vitro and in vivo, which is suggestive
      of a novel regulatory network between the innate immune response and tumor
      suppression.

PMID- 18056438
TI  - Role of CYP2E1 in diethylnitrosamine-induced hepatocarcinogenesis in vivo.
AB  - CYP2E1 metabolizes many low-molecular weight toxins and carcinogens. Some in
      vitro experiments suggest that CYP2E1 may be involved in the metabolic activation
      of diethylnitrosamine. However, there has been no direct evidence demonstrating a
      role for CYP2E1 in diethylnitrosamine-mediated carcinogenesis in vivo. To clarify
      this, we carried out a diethylnitrosamine-induced hepatocarcinogenesis experiment
      using Cyp2e1-null mice. Male 14-day-old wild-type and Cyp2e1-null mice were
      treated with diethylnitrosamine (10 mg/kg of body weight) and killed at weeks 24
      and 36 after diethylnitrosamine treatment for investigation of tumors and at 6,
      24, and 48 h for examination of apoptosis and gene expression. Liver weights of
      Cyp2e1-null mice were significantly different at weeks 24 and 36 compared with
      wild-type mice (P < 0.01). Liver tumor incidences of Cyp2e1-null mice were
      significantly decreased at weeks 24 and 36 compared with wild-type mice (P <
      0.01). Cyp2e1-null mice showed significant decrease in the multiplicities of
      hepatocellular adenoma at weeks 24 and 36 (P < 0.05 and P < 0.01, respectively),
      and of hepatocellular carcinoma at week 36 (P < 0.01) compared with wild-type
      mice. Apoptotic index and caspase-3 and/or Bax mRNA expression of Cyp2e1-null
      mice were significantly different at 6, 24, and 48 h after diethylnitrosamine
      treatment compared with wild-type mice (P < 0.05). We conclude that Cyp2e1-null
      mice show lower tumor incidence and multiplicity compared with wild-type mice in
      diethylnitrosamine-induced hepatocarcinogenesis. It is suggested that CYP2E1
      completely participates in diethylnitrosamine-induced hepatocarcinogenesis, and
      high frequency of tumors in wild-type mice could be associated with the increased
      apoptosis.

PMID- 18056439
TI  - Epithelial to mesenchymal transition in human breast epithelial cells transformed
      by 17beta-estradiol.
AB  - The estrogen dependence of breast cancer has long been recognized; however, the
      role of 17beta-estradiol (E(2)) in cancer initiation was not known until we
      showed that it induces complete neoplastic transformation of the human breast
      epithelial cells MCF-10F. E(2) treatment of MCF-10F cells progressively induced
      high colony efficiency and loss of ductulogenesis in early transformed (trMCF)
      cells and invasiveness in Matrigel invasion chambers. The cells that crossed the
      chamber membrane were collected and identified as bsMCF; their subclones were
      designated bcMCF; and the cells harvested from carcinoma formation in severe
      combined immunodeficient mice were designated caMCF. These phenotypes correlated
      with gene dysregulation during the progression of the transformation. The highest
      number of dysregulated genes was observed in caMCF, being slightly lower in
      bcMCF, and lowest in trMCF. This order was consistent with the extent of
      chromosome aberrations (caMCF > bcMCF >>> trMCF). Chromosomal amplifications were
      found in 1p36.12-pter, 5q21.1-qter, and 13q21.31-qter. Losses of the complete
      chromosome 4 and 8p11.21-23.1 were found only in tumorigenic cells. In tumor
      derived cell lines, additional losses were found in 3p12.1-14.1, 9p22.1-pter, and
      18q11.21-qter. Functional profiling of dysregulated genes revealed progressive
      changes in the integrin signaling pathway, inhibition of apoptosis, acquisition
      of tumorigenic cell surface markers, and epithelial-mesenchymal transition. In
      tumorigenic cells, the levels of E-cadherin, epithelial membrane antigen, and
      various keratins were low and CD44E/CD24 were negative, whereas SNAI2, vimentin,
      S100A4, FN1, HRAS, transforming growth factor beta1, and CD44H were high. The
      phenotypic and genomic changes triggered by estrogen exposure that lead normal
      cells to tumorigenesis confirm the role of this steroid hormone in cancer
      initiation.

PMID- 18056440
TI  - Novel NBS1 heterozygous germ line mutation causing MRE11-binding domain loss
      predisposes to common types of cancer.
AB  - DNA damage response (DDR) pathways maintain genomic stability. A 657del5 mutation
      of NBS1, a key DDR component, causing the rare cancer-predisposing Nijmegen
      breakage syndrome has been reported nearly exclusively in Slavic populations. In
      this study, we describe the first identification in a Japanese population of an
      unprecedented type of heterozygous NBS1 mutant, termed IVS11+2insT, lacking the
      MRE11- and ATM-binding site at the COOH terminus. Profoundly defective in crucial
      binding to MRE11, MDC1, BRCA1, and wild-type NBS1, the mutant caused impaired ATM
      phosphorylation in response to low-dose irradiation in a heterozygous state.
      Importantly, whereas IVS11+2insT was found in only 2 (0.09%) of 2,348 control
      subjects, it was identified in 2% (2 of 96) of heterozygotes with gastric cancer,
      0.8% (3 of 376) of those with colorectal cancer, and 0.4% (2 of 532) of those
      with lung cancer, which were comparable to frequencies reported for other DDR
      related genes known to confer cancer susceptibility. The presence of the
      heterozygous IVS11+2insT mutation seemed to be associated with an increased risk
      for gastrointestinal cancers, with an odds ratio of 12.6 and 95% confidence
      interval (95% CI) of 2.05 to 132.1 (P = 0.0001). The odds ratios separately
      calculated for gastric and colorectal cancers were 25.0 (95% CI, 1.78-346.0) and
      9.43 (95% CI, 1.08-113.1), respectively. These findings suggest that IVS11+2insT
      is associated with an increased risk for the development of certain types of
      common cancers, warranting future investigation including detailed phenotypic
      characterization of age of onset and penetrance in heterozygotes, as well as
      screening in other ethnic groups.

PMID- 18056441
TI  - Sigma-1 receptors bind cholesterol and remodel lipid rafts in breast cancer cell
      lines.
AB  - Lipid rafts are membrane platforms that spatially organize molecules for specific
      signaling pathways that regulate various cellular functions. Cholesterol is
      critical for liquid-ordered raft formation by serving as a spacer between the
      hydrocarbon chains of sphingolipids, and alterations in the cholesterol contents
      of the plasma membrane causes disruption of rafts. The role that sigma receptors
      play in cancer is not clear, although it is frequently up-regulated in human
      cancer cells and tissues and sigma receptors inhibit proliferation in carcinoma
      and melanoma cell lines, induce apoptosis in colon and mammary carcinoma cell
      lines, and reduce cellular adhesion in mammary carcinoma cell lines. In this
      study, we provide molecular and functional evidence for the involvement of the
      enigmatic sigma 1 receptors in lipid raft modeling by sigma 1 receptor-mediated
      cholesterol alteration of lipid rafts in breast cancer cell lines. Cholesterol
      binds to cholesterol recognition domains in the COOH terminus of the sigma 1
      receptor. This binding is blocked by sigma receptor drugs because the cholesterol
      binding domains form part of the sigma receptor drug-binding site, mutations of
      which abolish cholesterol binding. Furthermore, we outline a hypothetical
      functional model to explain the myriad of biological processes, including cancer,
      in which these mysterious receptors are involved. The findings of this study
      provide a biological basis for the potential therapeutic applications of lipid
      raft cholesterol regulation in cancer therapy using sigma receptor drugs.

PMID- 18056442
TI  - Adaptor protein LAPF recruits phosphorylated p53 to lysosomes and triggers
      lysosomal destabilization in apoptosis.
AB  - Evidence suggests a functional association between the tumor suppressor p53 and
      apoptosis-involved organelle lysosome; however, the detailed mechanisms remain
      poorly understood. We recently reported that a lysosome-targeting protein, LAPF
      (lysosome-associated and apoptosis-inducing protein containing PH and FYVE
      domains), could initiate apoptosis of L929 cells through a lysosomal
      mitochondrial pathway. In this study, we show that LAPF specifically interacted
      with phosphorylated p53 (Ser(15/18)) both in vitro and in vivo, which could be
      enhanced by apoptotic stimuli, such as tumor necrosis factor alpha (TNF-alpha)
      and ionizing irradiation. The PH domain of LAPF and the transactivation domain of
      p53 mediated the interaction between both molecules. Phosphorylated p53
      (Ser(15/18)) could translocate to lysosomes before lysosomal membrane
      permeabilization (LMP) in LAPF-initiated and TNF-induced apoptosis. Silencing of
      LAPF expression abrogated lysosomal translocation of phosphorylated p53
      (Ser(15/18)), whereas silencing of p53 expression had no effect on lysosomal
      translocation of LAPF. Similar to that of LAPF silencing, silencing of endogenous
      p53 expression in L929 cells could significantly impair TNF-alpha-induced LMP and
      apoptosis. However, reexpression of wild-type p53, p53S15D (substitution of
      Ser(15) to Asp that mimics a phosphorylated state), and p53R175H (a transcription
      deficient mutant) in p53-knockdown L929 cells could rescue the decrease in TNF
      induced apoptosis. The data suggest that phosphorylated p53 (Ser(15/18)) might
      translocate to lysosome via forming complexes with adaptor protein LAPF and
      subsequently result in LMP and apoptosis, which might be in a transcription
      independent manner.

PMID- 18056443
TI  - Aurora-A kinase regulates breast cancer associated gene 1 inhibition of
      centrosome-dependent microtubule nucleation.
AB  - Breast cancer-associated gene 1 (BRCA1) regulates the duplication and the
      function of centrosomes in breast cells. We have previously shown that BRCA1
      ubiquitin ligase activity directly inhibits centrosome-dependent microtubule
      nucleation. However, there is a paradox because centrosome microtubule nucleation
      potential is highest during mitosis, a phase when BRCA1 is most abundant at the
      centrosome. In this study, we resolve this conundrum by testing whether
      centrosomes from cells in M phase are regulated differently by BRCA1 when
      compared with other phases of the cell cycle. We observed that BRCA1-dependent
      inhibition of centrosome microtubule nucleation was high in S phase but was
      significantly lower during M phase. The cell cycle-specific effects of BRCA1 on
      centrosome-dependent microtubule nucleation were detected in living cells and in
      cell-free experiments using centrosomes purified from cells at specific stages of
      the cell cycle. We show that Aurora-A kinase modulates the BRCA1 inhibition of
      centrosome function by decreasing the E3 ubiquitin ligase activity of BRCA1. In
      addition, dephosphorylation of BRCA1 by protein phosphatase 1 alpha enhances the
      E3 ubiquitin ligase activity of BRCA1. These observations reveal that the
      inhibition of centrosome microtubule nucleation potential by the BRCA1 E3
      ubiquitin ligase is controlled by Aurora-A kinase and protein phosphatase 1 alpha
      mediated phosphoregulation through the different phases of the cell cycle.

PMID- 18056444
TI  - Differing phenotypes between intraepithelial and stromal lymphocytes in early
      stage tongue cancer.
AB  - The significance of tumor-infiltrating lymphocytes (TIL) has attracted much
      attention in relation to the prognosis of patients. We herein examined the
      activation status of the TILs in relation to the tumor microenvironment. By using
      frozen sections of human early-stage tongue cancers (n = 22), the TILs in the
      cancer nests and those in the cancer stroma were compared for the expression of
      PD-1, NKG2A, NKG2D, CD69, and Ki-67. The lymphocytes in oral lichen planus, an
      active immune response-mediated mucosal disease, were also analyzed for
      comparison purposes. All of the cancer specimens were abundantly infiltrated by
      CD8(+) T cells and CD56(+) natural killer (NK) cells in the stroma, as well as in
      the tumor nest. The tumor nest-infiltrating (intraepithelial) CD8(+) T cells
      frequently expressed PD-1, an inhibitory receptor, in sharp contrast to those in
      the stroma or in the lichen planus. Conversely, the intraepithelial CD8(+) T
      cells only infrequently expressed NKG2D, an activating receptor, in contrast to
      those in the stroma or in the lichen planus. No intraepithelial CD8(+) T cells
      expressed Ki-67, a proliferation-associated marker, whereas those in the stroma
      frequently expressed it. Furthermore, the intraepithelial NK cells expressed
      NKG2A, an inhibitory receptor, more frequently than those in the stroma or the
      lichen planus. Collectively, the intraepithelial CD8(+) T cells and NK cells are
      phenotypically inactivated, whereas stromal counterparts are phenotypically just
      as active as those in the lichen planus. These results suggest the first-step
      occurrence of an immune evasion mechanism in the tumor nest of oral squamous cell
      carcinoma.

PMID- 18056445
TI  - CD83 gene polymorphisms increase susceptibility to human invasive cervical
      cancer.
AB  - We previously mapped a nonrandom frequent loss of heterozygosity (LOH) region in
      cervical cancers to 1 Mb of 6p23. Here, we describe the identification of a novel
      cervical cancer susceptibility gene, CD83. The gene was identified by several
      complementary approaches, including a family-based association study, comparison
      of transcript expression in normal and cancerous tissue, and genomic sequencing
      of candidate. CD83 encodes an inducible glycoprotein in the immunoglobulin
      superfamily and is a marker for mature dendritic cells. The association study
      that includes 377 family trios showed that five single nucleotide polymorphisms
      (SNP) within 8 kb of its 3'-end showed significant allelic association that was
      strengthened in a subgroup of women with invasive cancers infected by high-risk
      human papillomavirus type 16 and 18 (rs9296925, P = 0.0193; rs853360, P = 0.0035;
      rs9230, P = 0.0011; rs9370729, P = 0.0012; rs750749, P = 0.0133). Investigation
      of CD83 uncovered three alternative transcripts in cervical tissue and cell
      lines, with variant 3 (lacking exons 3 and 4) being more frequent in cervical
      cancer than in normal cervical epithelium (P = 0.0181). Genomic sequencing on 36
      paired normal and cervical tumors revealed several somatic mutations and novel
      SNPs in the promoter, exons, and introns of CD83. LOH was confirmed in >90% of
      cervical cancer specimens. Immunofluorescence colocalized CD83 protein to the
      Golgi apparatus and cell membrane of cervical cancer cell lines. None of seven
      nearby genes was differentially expressed in cervical cancer. The importance of
      CD83 in epithelial versus dendritic cells needs to be determined, as does its
      role in promoting cervical cancer.

PMID- 18056447
TI  - Traf1 induction and protection from tumor necrosis factor by nuclear factor
      kappaB p65 is independent of serine 536 phosphorylation.
AB  - Abnormal nuclear factor-kappaB (NF-kappaB) signaling has been attributed to the
      initiation and progression of cancer. Posttranslational modification of p65
      facilitates optimal NF-kappaB signaling after activation. Here, we show that the
      phosphorylation of serine 536 was required for p65-mediated transcription and I
      kappa B alpha expression in fibroblasts. Furthermore, tumor necrosis factor (TNF)
      treatment slightly induced p65 phosphorylation, and both unphosphorylated and
      phosphorylated p65 translocated into the nucleus. The phosphorylation of serine
      536 was not required for p65-mediated protection from TNF cytotoxicity and Traf1
      induction in fibroblasts. Also, the corecruitment of p65 and RNA polymerase II to
      the Traf1 enhancer region did not require p65 phosphorylation. However, the
      corecruitment of p65 and RNA polymerase II to the Csf2 promoter required the
      phosphorylation of serine 536. These findings suggested that the requirement of
      serine phosphorylation at residue 536 and the distance between the NF-kappaB
      response element and the start of transcription may influence which genes will be
      transcribed.

PMID- 18056446
TI  - c-myc Repression of TSC2 contributes to control of translation initiation and Myc
      induced transformation.
AB  - The c-myc oncogene plays a key role in cellular growth control, and translation
      initiation factors are among the transcriptional targets of Myc. Here, we
      describe a defect in translation initiation control in myc-null cells due to
      alterations in the mammalian target of rapamycin (mTOR) pathway. Myc loss
      increased sensitivity to dominant inhibition of eukaryotic translation initiation
      factor 4E function. Polysomal profiles of myc(-/-) cells revealed decreased
      translation initiation rates, which were accompanied by decreased 40S/60S
      ribosomal subunit ratios. Because the 40S small ribosomal subunit contains the
      key regulatory ribosomal protein S6 (rpS6), we considered that myc loss might
      affect expression of components of the mTOR signaling pathway that regulate rpS6
      function. Among mTOR signaling components, Myc directly affected transcription of
      tuberous sclerosis 2 (TSC2), as shown by quantitative mRNA analysis and by Myc
      binding to its promoter in chromatin immunoprecipitation assays. Importantly, Myc
      acted as a strong and direct repressor for TSC2 expression because its loss
      increased TSC2 mRNA in myc-null and in HL60 shRNA experiments, activation of a
      mycER construct in myc(-/-) cells suppressed TSC2 induction in a myc box II
      dependent manner, and mycER activation recruited Myc to the TSC2 promoter. The
      biological significance of the effect of Myc on TSC2 expression was shown by
      markedly reduced TSC2 mRNA levels in myc-transformed cells, stimulation of S6
      kinase activity in myc-null cells by TSC2 siRNA, and decreased Myc-induced soft
      agar colony formation following retroviral transduction of TSC2. Together, these
      findings show that regulation of TSC2 can contribute to the effects of Myc on
      cell proliferation and neoplastic growth.

PMID- 18056448
TI  - Identification of novel modifier loci of Apc Min affecting mammary tumor
      development.
AB  - Genetic background affects the susceptibility to mammary tumor development in
      Apc(Min/+) mice. Here we report the identification of four novel modifier loci
      that influence different aspects of mammary tumor development in Apc(Min/+) mice.
      Analysis of tumor development in a backcross of (FVBB6 Apc(Min/+)) x B6
      Apc(Min/+) mice has identified a modifier on chromosome 9 that significantly
      affects tumor multiplicity, and a modifier on chromosome 4 that significantly
      affects tumor latency and affects tumor number with suggestive significance. This
      modifier was also identified in a backcross involving 129X1/SvJ and B6 Apc(Min/+)
      mice. A modifier on chromosome 18 specifically affects tumor latency but not
      tumor number. Kaplan-Meier analysis suggests there is at least an additive
      interaction affecting tumor latency between the loci on chromosomes 4 and 18. We
      also identified a modifier locus on chromosome 6 that interacts with the loci on
      chromosome 4 and chromosome 9 to affect tumor number. These results suggest that
      multiple genetic loci control different aspects of mammary tumor development.
      None of these modifiers is associated with intestinal tumor susceptibility, which
      indicates that these modifiers act on tumor development in a tissue-specific
      manner.

PMID- 18056449
TI  - Neuroblastoma cells isolated from bone marrow metastases contain a naturally
      enriched tumor-initiating cell.
AB  - Neuroblastoma is a heterogeneous pediatric tumor thought to arise from the
      embryonic neural crest. Identification of the cell responsible for propagating
      neuroblastomas is essential to understanding this often recurrent, rapidly
      progressing disease. We have isolated and characterized putative tumor-initiating
      cells from 16 tumors and bone marrow metastases from patients in all
      neuroblastoma risk groups. Dissociated cells from tumors or bone marrow grew as
      spheres in conditions used to culture neural crest stem cells, were capable of
      self-renewal, and exhibited chromosomal aberrations typical of neuroblastoma.
      Primary spheres from all tumor risk groups differentiated under neurogenic
      conditions to form neurons. Tumor spheres from low-risk tumors frequently formed
      large neuronal networks, whereas those from high-risk tumors rarely did. As few
      as 10 passaged tumor sphere cells from aggressive neuroblastoma injected
      orthotopically into severe combined immunodeficient/Beige mice formed large
      neuroblastoma tumors that metastasized to liver, spleen, contralateral adrenal
      and kidney, and lung. Furthermore, highly tumorigenic tumor spheres were isolated
      from the bone marrow of patients in clinical remission, suggesting that this
      population of cells may predict clinical behavior and serve as a biomarker for
      minimal residual disease in high-risk patients. Our data indicate that high-risk
      neuroblastoma contains a cell with cancer stem cell properties that is enriched
      in tumor-initiating capacity. These cells may serve as a model system to identify
      the molecular determinants of neuroblastoma and to develop new therapeutic
      strategies for this tumor.

PMID- 18056450
TI  - Delta-like 4 Notch ligand regulates tumor angiogenesis, improves tumor vascular
      function, and promotes tumor growth in vivo.
AB  - The vascular endothelial growth factor (VEGF) plays a key role in tumor
      angiogenesis. However, clinical trials targeting the VEGF pathway are often
      ineffective, suggesting that other factors/pathways are also important in tumor
      angiogenesis. We have previously shown that the Notch ligand Delta-like 4 (DLL4)
      is up-regulated in tumor vasculature. Here, we show that DLL4, when expressed in
      tumor cells, functions as a negative regulator of tumor angiogenesis by reducing
      the number of blood vessels in all five types of xenografts, but acts as a
      positive driver for tumor growth in two of them (human glioblastoma and prostate
      cancer). The growth of in vivo models was not related to the effects on growth in
      vitro. DLL4 expressed in the tumor cells activated Notch signaling in host
      stromal/endothelial cells, increased blood vessel size, and improved vascular
      function within tumors. The promotion of tumor growth was, to some extent, due to
      a reduction of tumor hypoxia and apoptosis. DLL4-expressing tumor cells responded
      to anti-VEGF therapy with bevacizumab. A soluble form of DLL4 (D4ECD-Fc) blocked
      tumor growth in both bevacizumab-sensitive and bevacizumab-resistant tumors by
      disrupting vascular function despite increased tumor vessel density. In addition,
      we show that DLL4 is up-regulated in tumor cells and tumor endothelial cells of
      human glioblastoma. Our findings provide a rational basis for the development of
      novel antiangiogenic strategies via blockade of DLL4/Notch signaling and suggest
      that combined approaches for interrupting both DLL4 and VEGF pathways may improve
      antiangiogenic therapy.

PMID- 18056451
TI  - Epithelial-mesenchymal transition events during human embryonic stem cell
      differentiation.
AB  - Epithelial-mesenchymal transition (EMT) occurs during embryonic development and
      may also be associated with the metastatic spread of epithelial tumors. During
      EMT, E-cadherin is down-regulated and this correlates with increased motility and
      invasion of cells. We show that differentiation of human embryonic stem (ES)
      cells in monolayer culture is associated with an E- to N-cadherin switch,
      increased vimentin expression, up-regulation of E-cadherin repressor molecules
      (Snail and Slug proteins), and increased gelatinase (matrix metalloproteinases;
      MMP-2 and MMP-9) activity and cellular motility, all characteristic EMT events.
      The 5T4 oncofetal antigen, previously shown to be associated with early human ES
      cell differentiation, is also part of this process. Abrogation of E-cadherin
      mediated cell-cell contact in undifferentiated ES cells using neutralizing
      antibody (nAb) SHE78.7 resulted in increased cellular motility, altered actin
      cytoskeleton arrangement and a mesenchymal phenotype together with presentation
      of the 5T4 antigen at the cell surface. nAb-treated ES cells remained in an
      undifferentiated state, as assessed by OCT-4 protein expression, and did not
      express EMT-associated transcripts. Removal of nAb from ES cells resulted in the
      restoration of cell-cell contact, absence of cell surface 5T4, decreased
      mesenchymal cellular morphology and motility, and enabled the differentiation of
      the cells to the three germ layers upon their removal from the fibroblast feeder
      layer. We conclude that E-cadherin functions in human ES cells to stabilize the
      cortical actin cyoskeletal arrangement and this prevents cell surface
      localization of the 5T4 antigen. Furthermore, human ES cells represent a useful
      model system with which to study EMT events relevant to embryonic development and
      tumor cell metastasis.

PMID- 18056452
TI  - Runx2 disruption promotes immortalization and confers resistance to oncogene
      induced senescence in primary murine fibroblasts.
AB  - The Runx genes play paradoxical roles in cancer where they can function either as
      dominant oncogenes or tumor suppressors according to context. We now show that
      the ability to induce premature senescence in primary murine embryonic
      fibroblasts (MEF) is a common feature of all three Runx genes. However, ectopic
      Runx-induced senescence contrasts with Ras oncogene-induced senescence, as it
      occurs directly and lacks the hallmarks of proliferative stress. Moreover, a
      fundamental role for Runx function in the senescence program is indicated by the
      effects of Runx2 disruption, which renders MEFs prone to spontaneous
      immortalization and confers an early growth advantage that is resistant to stress
      induced growth arrest. Runx2(-/-) cells are refractory to H-Ras(V12)-induced
      premature senescence, despite the activation of a cascade of growth inhibitors
      and senescence markers, and are permissive for oncogenic transformation. The
      aberrant behavior of Runx2(-/-) cells is associated with signaling defects and
      elevated expression of S-G(2)-M cyclins and their associated cyclin dependent
      kinase activities that may override the effects of growth inhibitory signals.
      Coupling of stress responses to the cell cycle represents a novel facet of Runx
      tumor suppressor function and provides a rationale for the lineage-specific
      effects of loss of Runx function in cancer.

PMID- 18056453
TI  - Differential regulation of elafin in normal and tumor-derived mammary epithelial
      cells is mediated by CCAAT/enhancer binding protein beta.
AB  - CCAAT/enhancer binding protein beta (C/EBP beta) is a transcription factor
      implicated in the control of development, differentiation, and proliferation of
      mammary epithelial cells. However, it remains unclear how C/EBP beta is involved
      in tumor suppression through its interaction with specific downstream genes in
      breast cancer. Tumor cells overexpress serine proteases, which play crucial roles
      in tumor invasion and metastasis. Elafin is an endogenous serine protease
      inhibitor and is transcriptionally down-regulated in most tumor cell lines. In
      this study, we show that C/EBP beta is differentially expressed in normal versus
      tumor cell lines and normal adjacent versus tumor tissues obtained from breast
      cancer patients. We identified elafin as a downstream effector of C/EBP beta and
      show that elafin is also differentially regulated between normal and tumor cells.
      The mechanism by which C/EBP beta regulates elafin expression is through its
      direct interaction with the elafin promoter. There are three C/EBP beta binding
      sites involved in the elafin promoter activity, and the overexpression of C/EBP
      beta transactivates the elafin gene through these sites in tumor cells. RNA
      interference studies in normal cells further evidenced the requirement of the
      C/EBP beta for the elafin expression and negative feedback loop between C/EBP
      beta and elafin. We suggest that elafin is a novel substrate of C/EBP beta, and
      alterations in C/EBP beta isoforms result in their differential binding to the
      elafin promoter, leading to the altered expression of the elafin between normal
      and tumor cells.

PMID- 18056454
TI  - Choline kinase down-regulation increases the effect of 5-fluorouracil in breast
      cancer cells.
AB  - Identifying strategies to increase cancer cell kill while sparing normal tissue
      is critically important in cancer chemotherapy. Choline kinase (Chk), the enzyme
      that converts choline to phosphocholine (PC), is elevated in cancer cells and
      presents a novel target for increasing cell kill. Here, we have examined the
      effects of transiently down-regulating Chk by small interfering RNA against Chk
      (siRNA-chk) on PC and total choline-containing compound (tCho) levels and on the
      viability/proliferation of estrogen receptor-negative and estrogen receptor
      positive breast cancer cell lines and a nonmalignant mammary epithelial cell
      line. We investigated the effects of combination treatment with transient siRNA
      chk transfection and the anticancer drug 5-fluorouracil (5-FU) in those cell
      lines. Microarray analysis of the invasive estrogen receptor-negative MDA-MB-231
      cell line was done to characterize molecular changes associated with Chk down
      regulation. Chk down-regulation decreased PC and tCho levels in the malignant
      cell lines, whereas the cell viability/proliferation assays detected a decrease
      in proliferation in these cells. In contrast, Chk down-regulation had an almost
      negligible effect on PC and tCho levels as well as cell viability/proliferation
      in the nonmalignant cell line. A combination of siRNA-chk with 5-FU treatment
      resulted in a larger reduction of cell viability/proliferation in the breast
      cancer cell lines; this reduction was evident to a much lesser degree in the
      nonmalignant cells. Microarray analysis showed that Chk down-regulation affected
      33 proliferation-related genes and 9 DNA repair-related genes. Chk down
      regulation with siRNA-chk may provide a novel alternative to enhance the effect
      of anticancer drugs in malignant cells.

PMID- 18056455
TI  - WP1066 disrupts Janus kinase-2 and induces caspase-dependent apoptosis in acute
      myelogenous leukemia cells.
AB  - Several cytokines and growth factors that stimulate the proliferation of acute
      myelogenous leukemia (AML) cells transduce their signals by activating the
      transcription factor Janus-activated kinase 2 (JAK2). Accordingly, the inhibition
      of JAK2 or of its downstream signaling pathways suppresses the proliferation of
      AML cells. Because (E)-3(6-bromopyridin-2-yl)-2-cyano-N-((S0-1
      phenylethyl)acrylamide) (WP1066) is a novel analogue of the JAK2 inhibitor AG490,
      we tested its activity in AML cells and investigated its mechanism of action.
      Using clonogenic assays, we found that although WP1066 had a marginal effect on
      normal marrow progenitors, it inhibited the proliferation of AML colony-forming
      cells obtained from patients with newly diagnosed AML and that of the AML cell
      lines OCIM2 and K562. WP1066 inhibited OCIM2 cell multiplication by inducing
      accumulation of cells at the G(0)-G(1) phase of the cell cycle. Similar to its
      parent compound AG490, WP1066 inhibited the phosphorylation of JAK2, but unlike
      AG490, WP1066 also degraded JAK2 protein, thereby blocking its downstream signal
      transducer and activator of transcription (STAT) and phosphoinositide-3-kinase
      pathways. These effects resulted in the activation of the caspase pathway.
      Incubation of both OCIM2 and K562 cells with WP1066 activated caspase-3, induced
      cleavage of poly(ADP-ribose) polymerase, and caused caspase-dependent apoptotic
      cell death. Thus, WP1066 is a potent JAK2 inhibitor whose effects in AML and
      other hematologic malignancies merit further investigation.

PMID- 18056456
TI  - Targeting protein translation in human non small cell lung cancer via combined
      MEK and mammalian target of rapamycin suppression.
AB  - Lung cancer is a genetically heterogeneous disease characterized by the
      acquisition of somatic mutations in numerous protein kinases, including
      components of the rat sarcoma viral oncogene homolog (RAS) and AKT signaling
      cascades. These pathways intersect at various points, rendering this network
      highly redundant and suggesting that combined mitogen-activated
      protein/extracellular signal-regulated kinase (MEK) and mammalian target of
      rapamycin (mTOR) inhibition may be a promising drug combination that can overcome
      its intrinsic plasticity. The MEK inhibitors, CI-1040 or PD0325901, in
      combination with the mTOR inhibitor, rapamycin, or its analogue AP23573,
      exhibited dose-dependent synergism in human lung cancer cell lines that was
      associated with suppression of proliferation rather than enhancement of cell
      death. Concurrent suppression of MEK and mTOR inhibited ribosomal biogenesis by
      40% within 24 h and was associated with a decreased polysome/monosome ratio that
      is indicative of reduced protein translation efficiency. Furthermore, the
      combination of PD0325901 and rapamycin was significantly superior to either drug
      alone or PD0325901 at the maximum tolerated dose in nude mice bearing human lung
      tumor xenografts or heterotransplants. Except for a PTEN mutant, all tumor models
      had sustained tumor regressions and minimal toxicity. These data (a) provide
      evidence that both pathways converge on factors that regulate translation
      initiation and (b) support therapeutic strategies in lung cancer that
      simultaneously suppress the RAS and AKT signaling network.

PMID- 18056457
TI  - An oncolytic adenovirus redirected with a tumor-specific T-cell receptor.
AB  - To improve safety and specificity of oncolytic adenoviruses, we introduced T-cell
      receptors (TCR) specific for a unique class of truly tumor-specific antigens into
      the adenoviral fiber protein. The adenoviral fiber knob responsible for
      attachment to the coxsackie-adenoviral receptor (CAR) on target cells was
      replaced by a single-chain TCR (scTCR) molecule with specificity for the melanoma
      associated cancer-testis antigen MAGE-A1, presented by HLA-A1, and an extrinsic
      trimerization motif in a replicating Ad5 vector (Ad5.R1-scTCR). The production of
      the recombinant virus was initiated in a novel producer cell line that expressed
      an antibody-based hexon-specific receptor (293T-AdR) in the cell membrane. This
      new production system allowed CAR-independent and target antigen-independent
      propagation of Ad5.R1-scTCR. Infection with adenovirus bearing the scTCR-based
      fiber resulted in an efficient killing of target tumor cells. The infection was
      cell type specific because only HLA-A1(+)/MAGE-A1(+) melanoma cells were killed,
      and thus, this retargeting strategy provides a versatile tool for future clinical
      application.

PMID- 18056458
TI  - Ribosomal protein S27-like, a p53-inducible modulator of cell fate in response to
      genotoxic stress.
AB  - Activation of the p53 tumor suppressor upon DNA damage elicits either cell cycle
      arrest or apoptosis, and the precise mechanism governing cell fate after p53
      response has not been well defined. Through genomic analysis, we have identified
      the ribosomal protein S27-like (RPS27L) as a novel p53 transcriptional target
      gene. Although RPS27L mRNA levels were consistently induced after diverse p53
      activating signals, its change in protein level was stimuli-dependent: it was up
      regulated when cells were arrested in response to DNA-damaging agents Adriamycin
      or VP16 but was down-regulated when cells underwent apoptosis in response to
      antimetabolite agent 5-fluorouracil. RPS27L is a nuclear protein that forms
      nuclear foci upon DNA damage. Depletion of RPS27L resulted in deficiency in DNA
      damage checkpoints, leading to conversion of DNA damage-induced p53 response from
      cell cycle arrest to apoptosis. We further show that RPS27L positively regulates
      p21 protein expression. Through this mechanism, RPS27L induction by p53
      facilitates p21-mediated cell cycle arrest and protects against DNA damage
      induced apoptosis. Thus, RPS27L modulates DNA damage response and functions as a
      part of the control switch to determine cell fate to DNA damage-p53 response.

PMID- 18056459
TI  - Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET.
AB  - Histone deacetylase inhibitors (HDIs) and HAMLET (human alpha-lactalbumin made
      lethal to tumor cells) interact with histones, modify the structure of chromatin,
      and trigger tumor cell death. This study investigated how the combination of HDIs
      and HAMLET influences cell viability, histone acetylation, and DNA integrity. The
      pretreatment of tumor cells with HDIs was shown to enhance the lethal effect of
      HAMLET and the histone hyperacetylation response to HDIs increased even further
      after HAMLET treatment. HDIs and HAMLET were shown to target different histone
      domains as HAMLET bound tailless core histones, whereas HDIs modify the
      acetylation of the histone tail. DNA damage in response to HAMLET was increased
      by HDIs. The DNA repair response (p21WAFI expression) was induced by both
      agonists but abolished when the two agonists were combined. The results suggest
      that the synergy of HDIs and HAMLET is based on different but converging death
      pathways, both involving chromatin alterations. We speculate that HAMLET and HDIs
      might be combined to promote tumor cell death in vivo.

PMID- 18056460
TI  - Drug sensitivity prediction by CpG island methylation profile in the NCI-60
      cancer cell line panel.
AB  - Aberrant promoter hypermethylation and associated gene silencing are epigenetic
      hallmarks of tumorigenesis. It has been suggested that aberrant DNA methylation
      can affect the sensitivity of cancers to antineoplastic agents by altering
      expression of genes critical to drug response. To study this issue, we used
      bisulfite PCR to assess DNA methylation of 32 promoter-associated CpG islands in
      human cancer cell lines from the National Cancer Institute (NCI) drug-screening
      panel (NCI-60 panel). The frequency of aberrant hypermethylation of these islands
      ranged from 2% to 81% in NCI-60 cancer cells, and provided a database that can be
      analyzed for the sensitivity to approximately 30,000 drugs tested in this panel.
      By correlating drug activity with DNA methylation, we identified a list of
      methylation markers that predict sensitivity to chemotherapeutic drugs. Among
      them, hypermethylation of the p53 homologue p73 and associated gene silencing was
      strongly correlated with sensitivity to alkylating agents. We used small
      interfering RNA to down-regulate p73 expression in multiple cell lines, including
      the resistant cell lines TK10 (renal cancer) and SKMEL28 (melanoma). Down
      regulating p73 substantially increased sensitivity to commonly used alkylating
      agents, including cisplatin, indicating that epigenetic silencing of p73 directly
      modulates drug sensitivity. Our results confirm that epigenetic profiles are
      useful in identifying molecular mediators for cancer drug sensitivity (pharmaco
      epigenomics).

PMID- 18056461
TI  - Novel quinazoline-based compounds impair prostate tumorigenesis by targeting
      tumor vascularity.
AB  - Previous evidence showed the ability of the quinazoline-based alpha(1)
      adrenoreceptor antagonist doxazosin to suppress prostate tumor growth via
      apoptosis. In this study, we carried out structural optimization of the chemical
      nucleus of doxazosin and a subsequent structure-function analysis toward the
      development of a novel class of apoptosis-inducing and angiogenesis-targeting
      agents. Our lead compound, DZ-50, was effective at reducing endothelial cell
      viability via a nonapoptotic mechanism. Treatment with DZ-50 effectively
      prevented in vitro tube formation and in vivo chorioallantoic membrane vessel
      development. Confocal microscopy revealed a significantly reduced ability of
      tumor cells to attach to extracellular matrix and migrate through endothelial
      cells in the presence of DZ-50. In vivo tumorigenicty studies using two androgen
      independent human prostate cancer xenografts, PC-3 and DU-145, showed that DZ-50
      treatment leads to significant suppression of tumorigenic growth. Exposure to the
      drug at the time of tumor cell inoculation led to prevention of prostate cancer
      initiation. Furthermore, DZ-50 resulted in a reduced formation of prostate-tumor
      derived metastatic lesions to the lungs in an in vivo spontaneous metastasis
      assay. Thus, our drug discovery approach led to the development of a class of
      lead (quinazoline-based) compounds with higher potency than doxazosin in
      suppressing prostate growth by targeting tissue vascularity. This new class of
      quinazoline-based compounds provides considerable promise as antitumor drugs for
      the treatment of advanced prostate cancer.

PMID- 18056462
TI  - Gpx2 is an overexpressed gene in rat breast cancers induced by three different
      chemical carcinogens.
AB  - Gene expression alterations are essential for the process of carcinogenesis. A
      carcinogen may have specific mechanisms for inducing tumors, which may involve
      inducing characteristic gene expression alterations. In this study, we attempted
      to identify genes crucial for mammary carcinogenesis. For this purpose, we used
      human c-Ha-ras proto-oncogene transgenic rats (Hras128), which are highly
      sensitive to mammary carcinogens including N-methyl-N-nitrosourea, 7,12-dimethyl
      benz[a]anthracene, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. DNA
      microarray analysis revealed that glutathione peroxidase 2 (Gpx2) was commonly up
      regulated in the mammary carcinomas induced by the three different carcinogens,
      and its up-regulation was confirmed by quantitative reverse transcriptase-PCR and
      Western blotting analysis. In addition, expression of GPX2 was recognized in all
      41 immunohistochemically examined cases of human breast cancer. Forced
      suppression of GPX2 expression by siRNA resulted in significant growth inhibition
      in both rat and human mammary carcinoma cell lines with wild-type p53 cells.
      Thus, these data suggested that GPX2 may be involved in mammary carcinogenesis
      and cell proliferation in both rats and humans, indicating that GPX2 may be a
      novel target for the prevention and therapy of breast cancer.

PMID- 18056463
TI  - The novel combination of chlorpromazine and pentamidine exerts synergistic
      antiproliferative effects through dual mitotic action.
AB  - Combination therapy has proven successful in treating a wide variety of
      aggressive human cancers. Historically, combination treatments have been
      discovered through serendipity or lengthy trials using known anticancer agents
      with similar indications. We have used combination high-throughput screening to
      discover the unexpected synergistic combination of an antiparasitic agent,
      pentamidine, and a phenothiazine antipsychotic, chlorpromazine. This combination,
      CRx-026, inhibits the growth of tumor cell lines in vivo more effectively than
      either pentamidine or chlorpromazine alone. Here, we report that CRx-026 exerts
      its antiproliferative effect through synergistic dual mitotic action.
      Chlorpromazine is a potent and specific inhibitor of the mitotic kinesin KSP/Eg5
      and inhibits tumor cell proliferation through mitotic arrest and accumulation of
      monopolar spindles. Pentamidine treatment results in chromosomal segregation
      defects and delayed progression through mitosis, consistent with inhibition of
      the phosphatase of regenerating liver family of phosphatases. We also show that
      CRx-026 synergizes in vitro and in vivo with the microtubule-binding agents
      paclitaxel and vinorelbine. These data support a model where dual action of
      pentamidine and chlorpromazine in mitosis results in synergistic antitumor
      effects and show the importance of systematic screening for combinations of
      targeted agents.

PMID- 18056464
TI  - Genetic alterations in the tyrosine kinase transcriptome of human cancer cell
      lines.
AB  - Protein tyrosine kinases (PTKs) play a critical role in the manifestation of
      cancer cell properties, and respective signaling mechanisms have been studied
      extensively on immortalized tumor cells. To characterize and analyze commonly
      used cancer cell lines with regard to variations in the primary structure of all
      expressed PTKs, we conducted a cDNA-based sequence analysis of the entire
      tyrosine kinase transcriptome of 254 established tumor cell lines. The profiles
      of cell line intrinsic PTK transcript alterations and the evaluation of 155
      identified polymorphisms and 234 somatic mutations are made available in a
      database designated "Tykiva" (tyrosine kinome variant). Tissue distribution
      analysis and/or the localization within defined protein domains indicate
      functional relevance of several genetic alterations. The cysteine replacement of
      the highly conserved Y367 residue in fibroblast growth factor receptor 4 or the
      Q26X nonsense mutation in the tumor-suppressor kinase CSK are examples, and may
      contribute to cell line-specific signaling characteristics and tumor progression.
      Moreover, known variants, such as epidermal growth factor receptor G719S, that
      were shown to mediate anticancer drug sensitivity could be detected in other than
      the previously reported tumor types. Our data therefore provide extensive system
      information for the design and interpretation of cell line-based cancer research,
      and may stimulate further investigations into broader clinical applications of
      current cancer therapeutics.

PMID- 18056465
TI  - Down-regulation of platelet-derived growth factor-D inhibits cell growth and
      angiogenesis through inactivation of Notch-1 and nuclear factor-kappaB signaling.
AB  - Platelet-derived growth factor-D (PDGF-D) signaling plays critical roles in the
      pathogenesis and progression of human malignancies; however, the precise
      mechanism by which PDGF-D causes tumor cell invasion and angiogenesis remain
      unclear. Because Notch-1, nuclear factor-kappaB (NF-kappaB), vascular endothelial
      growth factor (VEGF), and matrix metalloproteinases (MMP) are critically involved
      in the processes of tumor cell invasion and metastasis, we investigated whether
      PDGF-D down-regulation could be mechanistically associated with the down
      regulation of Notch-1, NF-kappaB, VEGF, and MMP-9, resulting in the inhibition of
      tumor cell invasion and angiogenesis. Our data showed that down-regulation of
      PDGF-D leads to the inactivation of Notch-1 and NF-kappaB DNA-binding activity
      and, in turn, down regulates the expression of its target genes, such as VEGF and
      MMP-9. We also found that the down-regulation of PDGF-D by small interfering RNA
      (siRNA) decreased tumor cell invasion, whereas PDGF-D overexpression by cDNA
      transfection led to increased cell invasion. Consistent with these results, we
      also found that the down-regulation of PDGF-D not only decreased MMP-9 mRNA and
      its protein expression but also inhibited the processing of pro-MMP-9 protein to
      its active form. Moreover, conditioned medium from PDGF-D siRNA-transfected cells
      showed reduced levels of VEGF and, in turn, inhibited the tube formation of human
      umbilical vascular endothelial cells, suggesting that down-regulation of PDGF-D
      leads to the inhibition of angiogenesis. Taken together, we conclude that the
      down-regulation of PDGF-D by novel approaches could lead to the down-regulation
      of Notch-1 and, in turn, inactivate NF-kappaB and its target genes (i.e., MMP-9
      and VEGF), resulting in the inhibition of invasion and angiogenesis.

PMID- 18056466
TI  - Automated, quantitative screening assay for antiangiogenic compounds using
      transgenic zebrafish.
AB  - Pathologic angiogenesis has emerged as an important therapeutic target in several
      major diseases. Zebrafish offer the potential for high-throughput drug discovery
      in a whole vertebrate system. We developed the first quantitative, automated
      assay for antiangiogenic compound identification using zebrafish embryos. This
      assay uses transgenic zebrafish with fluorescent blood vessels to facilitate
      image analysis. We developed methods for automated drugging and imaging of
      zebrafish in 384-well plates and developed a custom algorithm to quantify the
      number of angiogenic blood vessels in zebrafish. The assay was used to screen the
      LOPAC1280 compound library for antiangiogenic compounds. Two known antiangiogenic
      compounds, SU4312 and AG1478, were identified as hits. Additionally, one compound
      with no previously known antiangiogenic activity, indirubin-3'-monoxime (IRO),
      was identified. We showed that each of the hit compounds had dose-dependent
      antiangiogenic activity in zebrafish. The IC(50) of SU4312, AG1478, and IRO in
      the zebrafish angiogenesis assay was 1.8, 8.5, and 0.31 micromol/L, respectively.
      IRO had the highest potency of the hit compounds. Moreover, IRO inhibited human
      umbilical vein endothelial cell tube formation and proliferation (IC(50) of 6.5
      and 0.36 micromol/L, respectively). It is therefore the first antiangiogenic
      compound discovered initially in a zebrafish assay that also has demonstrable
      activity in human endothelial cell-based angiogenesis assays.

PMID- 18056467
TI  - Cks1 regulates cdk1 expression: a novel role during mitotic entry in breast
      cancer cells.
AB  - Cks1, a small protein whose expression is strongly associated with aggressive
      breast tumors, is a component of cyclin-cdk complexes, as well as the SCF(Skp2)
      ubiquitin ligase. In these studies, we explored its roles in estrogen receptor
      positive breast tumor cells. When exposed to the antiestrogen ICI 182780, these
      cells accumulate in G(1) by reducing the expression of Cks1, and increasing the
      levels of p130/Rb2, a cdk2 inhibitor and SCF(Skp2) target. Heregulin beta1 or
      estradiol abrogate antiestrogen effects by increasing Cks1 expression, down
      regulating p130/Rb2 and inducing S phase entry. Depletion of Cks1 in these cells
      by RNA interference concomitantly decreased Skp2 and up-regulated p130/Rb2 and
      another SCF(Skp2) target, p27(Kip1). Remarkably, however, Cks1-depleted cells not
      only exhibit slowed G(1) progression, but also accumulate in G(2)-M due to
      blocked mitotic entry. Notably, we show that cdk1 expression, which is crucial
      for M phase entry, is drastically diminished by Cks1 depletion, and that
      restoration of cdk1 reduces G(2)-M accumulation in Cks1-depleted cells. cdk1
      reduction in Cks1-depleted cells is a consequence of a marked decrease in its
      mRNA and not due to alteration in its proteolytic turnover. Both heregulin beta1
      and estradiol could neither restore cdk1 nor sustain cycling in Cks1-depleted
      cells, although classical estrogen receptor function remained unaltered. Cks1
      depletion also decreased Skp2 in human mammary epithelial cells without altering
      cell cycle progression. Thus, the indispensability of Cks1 to the breast cancer
      cell cycle, versus its redundancy in normal cells, suggests that Cks1 abrogation
      could be an effective interventional strategy in breast cancer.

PMID- 18056468
TI  - The p38 MAPK pathway mediates aryl propionic acid induced messenger rna stability
      of p75 NTR in prostate cancer cells.
AB  - The p75(NTR) acts as a tumor suppressor in the prostate, but its expression is
      lost as prostate cancer progresses and is minimal in established prostate cancer
      cell lines such as PC-3, DU-145, and LNCaP. Previously, we showed that treatment
      with R-flurbiprofen or ibuprofen induced p75(NTR) expression in PC-3 and DU-145
      cells leading to p75(NTR)-mediated decreased survival. Here, we investigate the
      mechanism by which these drugs induce p75(NTR) expression. We show that the
      observed increase in p75(NTR) protein due to R-flurbiprofen and ibuprofen
      treatment was accompanied by an increase in p75(NTR) mRNA, and this increase in
      mRNA was the result of increased mRNA stability and not by an up-regulation of
      transcription. In addition, we show that treatment with R-flurbiprofen or
      ibuprofen led to sustained activation of the p38 mitogen-activated protein kinase
      (MAPK) pathway. Furthermore, inhibition of the p38 MAPK pathway with the p38 MAPK
      specific inhibitor SB202190 or by small interfering RNA (siRNA) knockdown of p38
      MAPK protein prevented induction of p75(NTR) by R-flurbiprofen and ibuprofen. We
      also observed that siRNA knockdown of MAPK-activated protein kinase (MK)-2 and
      MK3, the kinases downstream of p38 MAPK that are responsible for the mRNA
      stabilizing effects of the p38 MAPK pathway, also prevented an induction of
      p75(NTR) by R-flurbiprofen and ibuprofen. Finally, we identify the RNA
      stabilizing protein HuR and the posttranscriptional regulator eukaryotic
      translation initiation factor 4E as two possible mechanisms by which the p38 MAPK
      pathway may increase p75(NTR) expression. Collectively, the data suggest that R
      flurbiprofen and ibuprofen induce p75(NTR) expression by increased mRNA stability
      that is mediated through the p38 MAPK pathway.

PMID- 18056469
TI  - Identification of genes required for protection from doxorubicin by a genome-wide
      screen in Saccharomyces cerevisiae.
AB  - Anthracyclines are chemotherapeutic agents commonly used to treat a broad range
      of malignancies. Although effective, these drugs present serious complications,
      most notably cardiotoxicity. To determine the mechanisms that mediate
      cytoprotection from doxorubicin, we have screened the collection of Saccharomyces
      cerevisiae haploid gene deletion mutants. We have identified 71 deletion strains
      that display varying degrees of hypersensitivity to doxorubicin at a
      concentration that does not significantly reduce the viability of wild-type
      cells. Complementation of the doxorubicin-sensitive phenotype of the deletion
      strains with the wild-type genes proves that the sensitivity of the strain to
      doxorubicin is due to the gene deletion. The genes that mediate cytoprotection
      from doxorubicin belong to multiple pathways including DNA repair, RNA
      metabolism, chromatin remodeling, amino acid metabolism, and heat shock response.
      In addition, proteins with mitochondrial, osmosensing, vacuolar, and ribosomal
      functions are also required for protection from doxorubicin. We tested the
      sensitivity of the deletion strains to other cytotoxic agents, which resulted in
      different drug-specific sensitive groups. Most of the identified genes have
      mammalian homologues that participate in conserved pathways. Our data may prove
      useful to develop strategies aimed at sensitizing tumor cells to doxorubicin as
      well as protecting cardiac cells from its cytotoxic effects.

PMID- 18056470
TI  - Identification and characterization of a membrane receptor for proteolysis
      inducing factor on skeletal muscle.
AB  - Proteolysis-inducing factor (PIF) is a sulfated glycoprotein produced by cachexia
      inducing tumors, which induces atrophy of skeletal muscle. PIF has been shown to
      bind specifically with high affinity (K(d), in nanomolar) to sarcolemma membranes
      from skeletal muscle of both the mouse and the pig, as well as murine myoblasts
      and a human muscle cell line. Ligand binding was abolished after enzymatic
      deglycosylation, suggesting that binding was mediated through the oligosaccharide
      chains in PIF. Chondroitin sulfate, but not heparan or dermatan sulfate, showed
      competitive inhibition (K(d), 1.1 x 10(-7) mol/L) of binding of PIF to the
      receptor, suggesting an interaction with the sulfated oligosaccharide chains.
      Ligand blotting of [(35)S]PIF to triton solublized membranes from C(2)C(12) cells
      provided evidence for a binding protein of apparent M(r) of approximately 40,000.
      Amino acid sequence analysis showed the PIF receptor to be a DING protein.
      Antisera reactive to a 19mer from the N-terminal amino acid residues of the
      binding protein attenuated protein degradation and activation of the ubiquitin
      proteasome pathway induced by PIF in murine myotubes. In addition, the antisera
      was highly effective in attenuating the decrease in body weight in mice bearing
      the MAC16 tumor, with a significant increase in muscle wet weight due to an
      increase in the rate of protein synthesis, together with a reduction in protein
      degradation through attenuation of the increased proteasome expression and
      activity. These results confirm that the PIF binding protein has a functional
      role in muscle protein atrophy in cachexia and that it represents a potential new
      therapeutic target.

PMID- 18056471
TI  - Sustained antigen-specific antitumor recall response mediated by gene-modified
      CD4+ T helper-1 and CD8+ T cells.
AB  - Given that specific subsets of T helper 1 (Th1) and T helper 2 (Th2) CD4(+) T
      cells have been shown to play key roles in tumor rejection models, we wanted to
      assess the contribution of either Th1 or Th2 CD4(+) cell subtypes for redirected
      T-cell immunotherapy. In this study, we have developed a novel method involving
      retroviral transduction and in vitro T-cell polarization to generate gene
      engineered mouse CD4(+) Th1 and Th2 cells or T helper intermediate (Thi) cells
      expressing an anti-erbB2-CD28-zeta chimeric receptor. Gene-modified Th1 and Th2
      polarized CD4(+) cells were characterized by the preferential secretion of IFN
      gamma and interleukin-4, respectively, whereas Thi cells secreted both cytokines
      following receptor ligation. In adoptive transfer studies using an erbB2(+) lung
      metastasis model, complete survival of mice was observed when transduced Th1,
      Th2, or Thi CD4(+) cells were transferred in combination with an equivalent
      number of transduced CD8(+) T cells. Tumor rejection was consistently associated
      with transduced T cells at the tumor site and interleukin-2 secretion. However,
      the surviving mice treated with gene-modified Th1 CD4(+) cells were significantly
      more resistant to a subsequent challenge with a different erbB2(+) tumor (4T1.2)
      implanted s.c. This result correlated with both increased expansion of Th1 CD4(+)
      and CD8(+) T cells in the blood and a greater number of these cells localizing to
      the tumor site following rechallenge. These data support the use of gene-modified
      CD4(+) Th1 and CD8(+) T cells for mediating a sustained antitumor response.

PMID- 18056472
TI  - Amino-biphosphonate-mediated MMP-9 inhibition breaks the tumor-bone marrow axis
      responsible for myeloid-derived suppressor cell expansion and macrophage
      infiltration in tumor stroma.
AB  - BALB-neuT mice expressing an activated rat c-erbB-2/neu transgene under the mouse
      mammary tumor virus long terminal repeat show enhanced hematopoiesis with
      hyperproduction of myeloid-derived suppressor cells (MDSC) because of vascular
      endothelial growth factor (VEGF) secreted by the tumor. Here, we show that both
      tumor and stromal cells express matrix metalloproteinase-9 (MMP-9), thereby
      increasing the levels of pro-MMP-9 in the sera of tumor-bearing mice. Treatment
      with amino-biphosphonates impaired tumor growth, significantly decreased MMP-9
      expression and the number of macrophages in tumor stroma, and reduced MDSC
      expansion both in bone marrow and peripheral blood by dropping serum pro-MMP-9
      and VEGF. We dissected the role of tumor-derived MMP-9 from that secreted by
      stromal leukocytes by transplanting bone marrow from MMP-9 knockout mice into
      BALB-neuT mice. Although bone marrow progenitor-derived MMP-9 had a major role in
      driving MDSC expansion, amino-biphosphonate treatment of bone marrow chimeras
      further reduced both myelopoiesis and the supportive tumor stroma, thus enhancing
      tumor necrosis. Moreover, by reducing MDSC, amino-biphosphonates overcome the
      tumor-induced immune suppression and improved the generation and maintenance of
      antitumor immune response induced by immunization against the p185/HER-2. Our
      data reveal that suppression of MMP-9 activity breaks the vicious loop linking
      tumor growth and myeloid cell expansion, thus reducing immunosuppression. Amino
      biphosphonates disclose a specific MMP-9 inhibitory activity that may broaden
      their application above their current usage.

PMID- 18056473
TI  - Suppression of proximal T cell receptor signaling and lytic function in CD8+
      tumor-infiltrating T cells.
AB  - CD8(+) tumor-infiltrating lymphocytes (TIL) lack in vivo and in vitro lytic
      function due to a signaling deficit characterized by failure to flux calcium or
      activate tyrosine kinase activity upon contact with cognate tumor cells. Although
      CD3 zeta is phosphorylated by conjugation in vitro with cognate tumor cells,
      showing that TIL are triggered, PLC gamma-1, LAT, and ZAP70 are not activated and
      LFA-1 is not affinity-matured, and because p56(lck) is required for LFA-1
      activation, this implies that the signaling blockade is very proximal. Here, we
      show that TIL signaling defects are transient, being reversed upon purification
      and brief culture in vitro, implying a fast-acting "switch". Biochemical analysis
      of purified nonlytic TIL shows that contact with tumor cells causes transient
      activation of p56(lck) ( approximately 10 s) which is rapidly inactivated. In
      contrast, tumor-induced activation of p56(lck) in lytic TIL is sustained
      coincident with downstream TCR signaling and lytic function. Shp-1 is robustly
      active in nonlytic TIL compared with lytic TIL, colocalizes with p56(lck) in
      nonlytic TIL, and inhibition of Shp-1 activity in lytic TIL in vitro blocks tumor
      induced defective TIL cytolysis. Collectively, our data support the notion that
      contact of nonlytic TIL with tumor cells, and not with tumor-infiltrating myeloid
      derived suppressor cells, causes activation of Shp-1 that rapidly
      dephosphorylates the p56(lck) activation motif (Y394), thus inhibiting effector
      phase functions.

PMID- 18056474
TI  - The cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      activates the extracellular signal regulated kinase mitogen-activated protein
      kinase pathway.
AB  - During the cooking of meat, mutagenic and carcinogenic heterocyclic amines are
      formed, the most abundant of which, 2-amino-1-methyl-6-phenylimidazo[4-5
      b]pyridine (PhIP), induces tumors of the prostate, colon, and mammary gland in
      rats. Humans consuming cooked meat are exposed to PhIP on a daily basis, yet few
      studies have assessed the effects of PhIP at dietary relevant concentrations. In
      addition to its genotoxic properties, recent studies have shown that PhIP can
      activate estrogen receptor-mediated signaling pathways at doses that are similar
      to those that may be present in the body following consumption of a cooked meat
      meal. In the present study, we examined whether such doses of PhIP can affect
      estrogen receptor-independent signal transduction via the mitogen-activated
      protein kinase (MAPK) extracellular signal-related kinase (ERK) pathway to
      influence proliferation and migration in the human mammary epithelial cell line
      MCF10A and the prostate cancer cell line PC-3. At doses shown to have a
      proliferative effect on MCF10A cells (10(-11)-10(-7) mol/L), PhIP induced a
      rapid, transient increase in phosphorylation of both MAPK/ERK kinase 1/2 and
      ERKs. Inhibition of this pathway significantly reduced the PhIP-induced
      proliferation of MCF10A cells and the migration of PC-3 cells. The data presented
      here show that levels of PhIP that approximate to human dietary exposure
      stimulate cellular signaling pathways and result in increased growth and
      migration, processes linked to the promotion and progression of neoplastic
      disease. These findings provide strong evidence that PhIP acts as a tumor
      initiator and promoter and that dietary exposure to this compound could
      contribute to carcinogenesis in humans.

PMID- 18056475
TI  - 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography is a sensitive
      method for imaging the response of BRAF-dependent tumors to MEK inhibition.
AB  - Activating mutations of BRAF occur in approximately 7% of all human tumors and in
      the majority of melanomas. These tumors are very sensitive to pharmacologic
      inhibition of mitogen-activated protein kinase/extracellular signal-regulated
      kinase kinase (MEK), which causes loss of D-cyclin expression,
      hypophosphorylation of Rb, and G(1) arrest. Growth arrest is followed by
      differentiation or senescence and, in a subset of BRAF mutant tumors, by
      apoptosis. The former effects result in so-called "stable disease" and, in
      patients with cancer, can be difficult to distinguish from indolent tumor growth.
      The profound G(1) arrest induced by MEK inhibition in BRAF mutant tumors is
      associated with a marked decline in thymidine uptake and is therefore potentially
      detectable in vivo by noninvasive 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT)
      positron emission tomography (PET) imaging. In SKMEL-28 tumor xenografts, MEK
      inhibition completely inhibited tumor growth and induced differentiation with
      only modest tumor regression. MEK inhibition also resulted in a rapid decline in
      the [(18)F]FLT signal in V600E BRAF mutant SKMEL-28 xenografts but not in BRAF
      wild-type BT-474 xenografts. The data suggest that [(18)F]FLT PET can effectively
      image induction of G(1) arrest by MEK inhibitors in mutant BRAF tumors and may be
      a useful noninvasive method for assessing the early biological response to this
      class of drugs.

PMID- 18056476
TI  - MisR/MisS two-component regulon in Neisseria meningitidis.
AB  - Two-component regulatory systems are involved in processes important for
      bacterial pathogenesis. Inactivation of the misR/misS system in Neisseria
      meningitidis results in the loss of phosphorylation of the lipooligosaccharide
      inner core and causes attenuation in a mouse model of meningococcal infection.
      One hundred seventeen (78 up-regulated and 39 down-regulated) potential
      regulatory targets of the MisR/MisS (MisR/S) system were identified by
      transcriptional profiling of the NMBmisR mutant and the parental wild-type
      meningococcal strain NMB. The regulatory effect was further confirmed in a subset
      of target genes by quantitative real-time PCR and beta-galactosidase
      transcriptional fusion reporter assays. The MisR regulon includes genes encoding
      proteins necessary for protein folding in the bacterial cytoplasm and periplasm,
      transcriptional regulation, metabolism, iron assimilation, and type I protein
      transport. Mutation in the MisR/S system caused increased sensitivity to
      oxidative stress and also resulted in decreased susceptibility to complement
      mediated killing by normal human serum. To identify the direct targets of MisR
      regulation, electrophoretic mobility shift assays were carried out using purified
      MisR-His(6) protein. Among 22 genes examined, misR directly interacted with 14
      promoter regions. Six promoters were further investigated by DNase I protection
      assays, and a MisR-binding consensus sequence was proposed. Thus, the direct
      regulatory targets of MisR and the minimal regulon of the meningococcal MisR/S
      two-component signal transduction system were characterized. These data indicate
      that the MisR/S system influences a wide range of biological functions in N.
      meningitidis either directly or via intermediate regulators.

PMID- 18056477
TI  - Neutrophils contribute to development of a protective immune response during
      onset of infection with Leishmania donovani.
AB  - Neutrophils are key components of the inflammatory response and as such
      contribute to the killing of microorganisms. In addition, recent evidence
      suggests their involvement in the development of the immune response. The role of
      neutrophils during the first weeks post-infection with Leishmania donovani was
      investigated in this study. When L. donovani-infected mice were selectively
      depleted of neutrophils with the NIMP-R14 monoclonal antibody, a significant
      increase in parasite numbers was observed in the spleen and bone marrow and to a
      lesser extent in the liver. Increased susceptibility was associated with enhanced
      splenomegally, a delay in the maturation of hepatic granulomas, and a decrease in
      inducible nitric oxide synthase expression within granulomas. In the spleen,
      neutrophil depletion was associated with a significant increase in interleukin 4
      (IL-4) and IL-10 levels and reduced gamma interferon secretion by CD4(+) and
      CD8(+) T cells. Increased production of serum IL-4 and IL-10 and higher levels of
      Leishmania-specific immunoglobulin G1 (IgG1) versus IgG2a revealed the
      preferential induction of Th2 responses in neutrophil-depleted mice. Altogether,
      these data suggest a critical role for neutrophils in the early protective
      response against L. donovani, both as effector cells involved in the killing of
      the parasites and as significant players influencing the development of a
      protective Th1 immune response.

PMID- 18056478
TI  - Listeria monocytogenes desensitizes immune cells to subsequent Ca2+ signaling via
      listeriolysin O-induced depletion of intracellular Ca2+ stores.
AB  - Listeriolysin O (LLO), the pore-forming toxin of Listeria monocytogenes, is a
      prototype of the cholesterol-dependent cytolysins (CDCs) secreted by several
      pathogenic and nonpathogenic gram-positive bacteria. In addition to mediating the
      escape of the bacterium into the cytosol, this toxin is generally believed to be
      a central player in host-pathogen interactions during L. monocytogenes infection.
      LLO triggers the influx of Ca(2+) into host cells as well as the release of
      Ca(2+) from intracellular stores. Thus, many of the cellular responses induced by
      LLO are related to calcium signaling. Interestingly, in this study, we report
      that prolonged exposure to LLO desensitizes cells to Ca(2+) mobilization upon
      subsequent stimulations with LLO. Cells preexposed to LLO-positive L.
      monocytogenes but not to the LLO-deficient Deltahly mutant were found to be
      highly refractory to Ca(2+) induction in response to receptor-mediated
      stimulation. Such cells also exhibited diminished Ca(2+) signals in response to
      stimulation with LLO and thapsigargin. The presented results suggest that this
      phenomenon is due to the depletion of intracellular Ca(2+) stores. The ability of
      LLO to desensitize immune cells provides a significant hint about the possible
      role played by CDCs in the evasion of the immune system by bacterial pathogens.

PMID- 18056479
TI  - Cross-species immunity in malaria vaccine development: two, three, or even four
      for the price of one?

PMID- 18056480
TI  - Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does
      not lead to differential signaling.
AB  - TLR are primary triggers of the innate immune system by recognizing various
      microorganisms through conserved pathogen-associated molecular patterns. TLR2 is
      the receptor for a functional recognition of bacterial lipopeptides (LP) and is
      up-regulated during various disorders such as chronic obstructive pulmonary
      disease and sepsis. This receptor is unique in its ability to form heteromers
      with TLR1 or TLR6 to mediate intracellular signaling. According to the fatty acid
      pattern as well as the assembling of the polypeptide tail, LP can signal through
      TLR2 in a TLR1- or TLR6-dependent manner. There are also di- and triacylated LP,
      which stimulate TLR1-deficient cells and TLR6-deficient cells. In this study, we
      investigated whether heterodimerization evolutionarily developed to broaden the
      ligand spectrum or to induce different immune responses. We analyzed the signal
      transduction pathways activated through the different TLR2 dimers using the three
      LP, palmitic acid (Pam)octanoic acid (Oct)(2)C-(VPGVG)(4)VPGKG, fibroblast
      stimulating LP-1, and Pam(2)C-SK(4). Dominant-negative forms of signaling
      molecules, immunoblotting of MAPK, as well as microarray analysis indicate that
      all dimers use the same signaling cascade, leading to an identical pattern of
      gene activation. We conclude that heterodimerization of TLR2 with TLR1 or TLR6
      evolutionarily developed to expand the ligand spectrum to enable the innate
      immune system to recognize the numerous, different structures of LP present in
      various pathogens. Thus, although mycoplasma and Gram-positive and Gram-negative
      bacteria may activate different TLR2 dimers, the development of different signal
      pathways in response to different LP does not seem to be of vital significance
      for the innate defense system.

PMID- 18056481
TI  - The IL-4Ralpha pathway in macrophages and its potential role in silica-induced
      pulmonary fibrosis.
AB  - Crystalline silica exposure can result in pulmonary fibrosis, where the pulmonary
      macrophage is key as a result of its ability to react to silica particles. In the
      mouse silicosis model, there is initial Th1-type inflammation, characterized by
      TNF-alpha and IFN-gamma. Previous studies determined that Th2 mediators (i.e., IL
      13) are vital to development of pulmonary fibrosis. The present study, using in
      vivo and in vitro techniques, compares silica exposures between Balb/c and Th2
      deficient mice in an effort to determine the link between Th2 immunity and
      silicosis. In long-term experiments, a significant increase in fibrosis and
      activated interstitial macrophages was observed in Balb/c but not IL-4Ralpha(-/-)
      mice. Additionally, a significant increase in Ym1 mRNA levels, a promoter of Th2
      immunity, was determined in the interstitial leukocyte population of silica
      exposed Balb/c mice. To elucidate the effects of silica on macrophage function,
      bone marrow-derived macrophages (BMdM) were exposed to particles and assayed for
      T cell (TC) stimulation activity. As a control, Ym1 mRNA expression in Balb/c
      BMdM was determined using IL-4 stimulation. In the in vitro assay, a significant
      increase in TC activation, as defined by surface markers and cytokines, was
      observed in the cultures containing the silica-exposed macrophages in wild-type
      and IL-4Ralpha(-/-) mice, with one exception: IL-4Ralpha(-/-) BMdM were unable to
      induce an increase in IL-13. These results suggest that crystalline silica alters
      cellular functions of macrophages, including activation of TC, and that the
      increase in Th2 immunity associated with silicosis is via the IL-4Ralpha-Ym1
      pathway.

PMID- 18056482
TI  - Lipopolysaccharide binding protein promoter variants influence the risk for Gram
      negative bacteremia and mortality after allogeneic hematopoietic cell
      transplantation.
AB  - Lipopolysaccharide binding protein (LBP) function is dependent on circulating LBP
      levels. Disturbance of LBP transcription regulation may influence the risk for
      clinical events. In a nested case-control study using a single nucleotide
      polymorphism haplotype tagging (tagSNP) approach, we assessed whether genetic
      variation in the LBP gene influences the risk for Gram-negative (GN) bacteremia
      after allogeneic hematopoietic cell transplantation (HCT), then validated the
      association in a prospective cohort by correlating genetic variation with basal
      serum LBP levels and mortality. Presence of the tagSNP 6878 C allele among
      patients was associated with a 2-fold higher risk for GN bacteremia (odds ratio =
      2.15; 95% confidence interval [CI], 1.31-3.52, P = .002). TagSNP 6878 was in
      strong linkage disequilibrium with 3 SNPs in the LBP promoter, one of which was
      SNP 1683 (r(2) = 0.8), located in a CAAT box that regulates LBP promoter
      efficiency. SNP 1683 was associated with higher median basal serum LBP levels (TT
      8.07 microg/mL; TC 10.40 microg/mL; CC 17.39 microg/mL; P = .002), and a 5-fold
      increase in GN bacteremia related mortality after HCT (hazard ratio = 4.83; 95%
      CI, 1.38-16.75, P = .013). These data suggest that transcriptional regulation of
      the LBP gene contributes to the risk for developing GN bacteremia and death after
      HCT.

PMID- 18056484
TI  - Semaphorin3A signaling controls Fas (CD95)-mediated apoptosis by promoting Fas
      translocation into lipid rafts.
AB  - Semaphorins and their receptors (plexins) have pleiotropic biologic functions,
      including regulation of immune responses. However, the role of these molecules
      inside the immune system and the signal transduction mechanism(s) they use are
      largely unknown. Here, we show that Semaphorin3A (Sema3A) triggers a proapoptotic
      program that sensitizes leukemic T cells to Fas (CD95)-mediated apoptosis. We
      found that Sema3A stimulation provoked Fas translocation into lipid raft
      microdomains before binding with agonistic antibody or FasL (CD95L). Disruption
      of lipid rafts reduced sensitivity to Fas-mediated apoptosis in the presence of
      Sema3A. Furthermore, we show that plexin-A1, together with Sema3A-binding
      neuropilin-1, was rapidly incorporated into membrane rafts after ligand
      stimulation, resulting in the transport of actin-linking proteins into Fas
      enriched rafts. Cells expressing a dominant-negative mutant of plexin-A1 did not
      show Fas clustering and apoptosis on Sema3A/Fas costimulation. This work
      identifies a novel biologic function of semaphorins and presents an unexpected
      signaling mechanism linking semaphorin to the tumor necrosis factor family
      receptors.

PMID- 18056483
TI  - A critical role for Lyn in acute myeloid leukemia.
AB  - Receptor or nonreceptor tyrosine kinases (TKs) are known to play an important
      role in leukemogenesis. Here we studied the level of protein tyrosine
      phosphorylations in a series of fresh AML samples and evaluated the effect of TK
      inhibitors. Compared with normal hematopoietic progenitors, a high level of
      tyrosine phosphorylation was detected in most acute myeloid leukemia (AML)
      samples. The Src family kinases (SFKs) appeared constitutively activated in most
      cases, including in the CD34(+)CD38(-)CD123(+) compartment as revealed by the
      level of phosphorylated tyrosine 416. Lyn was the major SFK family member
      expressed in an active form in AML cells where it was abnormally distributed
      throughout the plasma membrane and the cytosol as opposed to normal hematopoietic
      progenitors. The SFK inhibitor, PP2, strongly reduced the global level of
      tyrosine phosphorylations, inhibited cell proliferation, and induced apoptosis in
      patient samples without affecting normal granulomonocytic colony forming units.
      Moreover, silencing Lyn expression by small interfering RNA in primary AML cells
      strongly inhibited proliferation. Interestingly, a link between Lyn and the mTOR
      pathway was observed as PP2 and a Lyn knockdown both affected the phosphorylation
      of mTOR targets without inhibiting Akt phosphorylation. Lyn should be considered
      as a novel pharmacologic target for AML therapy.

PMID- 18056485
TI  - The sugar-binding ability of ERGIC-53 is enhanced by its interaction with MCFD2.
AB  - Combined deficiency of factors V and VIII (F5F8D) is a bleeding disorder caused
      by mutations in LMAN1 or MCFD2. LMAN1 encodes ERGIC-53, a cargo receptor with an
      L-type lectin domain, and MCFD2 is a EF-hand-containing protein. We prepared a
      biotinylated, soluble form of ERGIC-53, which we labeled with R-phycoerythrin
      conjugated streptavidin. By flow cytometry, sERGIC-53-SA bound to HeLaS3 cells in
      the presence of calcium but only after preincubation with MCFD2. Treating the
      cells with endo H or incubating them with high mannose-type oligosaccharides,
      especially M(8B), abrogated sERGIC-53-SA binding. Surface plasmon resonance
      experiments demonstrated that MCFD2 specifically bound to sERGIC-53 and 2 MCFD2
      mutants found in F5F8D patients had a K(a) that was 3 or 4 orders of magnitude
      lower for sERGIC-53 than for wild-type MCFD2. The K(a) of sERGIC-53 and MCFD2 was
      measured at several pH values and calcium concentrations, and we found that at a
      calcium concentration less than 0.2 mM, this interaction became significantly
      weaker. These results demonstrate that the binding of ERGIC-53 to sugar is
      enhanced by its interaction with MCFD2, and defects in this interaction in F5F8D
      patients may be the cause for reduced secretion of factors V and VIII.

PMID- 18056486
TI  - PAX2 expression by HHV-8-infected endothelial cells induced a proangiogenic and
      proinvasive phenotype.
AB  - In the present study, we evaluated whether infection of microvascular endothelial
      cells (HMECs) with HHV-8 can trigger the expression of PAX2 oncogene and whether
      PAX2 protein is involved in HHV-8-induced transformation of HMECs. We found that
      HHV-8 infection induced the expression of both the PAX2 gene and PAX2 protein in
      HMECs but failed to induce PAX2 protein in HMECs stably transfected with PAX2
      antisense (HMEC-AS). HHV-8-infected HMECs but not HMEC-AS acquired proinvasive
      proadhesive properties, enhanced survival and in vitro angiogenesis, suggesting a
      correlation between PAX2 expression and the effects triggered by HHV-8 infection.
      When HMEC-expressing PAX2 by stable transfection with PAX2 sense gene or by HHV-8
      infection were implanted in vivo in severe combined immunodeficient (SCID) mice,
      enhanced angiogenesis and proliferative lesions resembling KS were observed. HHV
      8-infected HMEC-AS failed to induce angiogenesis and KS-like lesions. These
      results suggest that the expression of PAX2 is required for the proangiogenic and
      proinvasive changes induced by HHV-8 infection in HMECs. In conclusion, HHV-8
      infection may activate an embryonic angiogenic program in HMECs by inducing the
      expression of PAX2 oncogene.

PMID- 18056488
TI  - Immediate mobilization compared with conventional immobilization for the impacted
      nonoperatively treated proximal humeral fracture. A randomized controlled trial.
AB  - BACKGROUND: There have been few randomized controlled trials evaluating
      nonoperative treatment of proximal humeral fractures. To investigate shortening
      the period of dependence, we assessed the feasibility and efficacy of early
      mobilization of the shoulder (within three days after the fracture) in comparison
      with those of conventional three-week immobilization followed by physiotherapy.
      METHODS: We randomly assigned seventy-four patients with an impacted proximal
      humeral fracture to receive early passive mobilization or conventional treatment.
      The primary outcome was the overall shoulder functional status (as measured with
      the Constant score) at three months. The secondary outcomes were the Constant
      score at six weeks and at six months, the change in pain (on a visual analog
      scale), and the active and passive range of motion. RESULTS: At three months and
      at six weeks, the early mobilization group had a significantly better Constant
      score than did the conventional-treatment group (between-group difference, 9.9
      [95% confidence interval, 1.9 to 17.8] [p = 0.02] and 10.1 [95% confidence
      interval, 2.0 to 18.1] [p = 0.02], respectively) and better active mobility in
      forward elevation (between-group difference, 12.0 [95% confidence interval, 1.7
      to 22.4] [p = 0.02] and 28.1 [95% confidence interval, 7.1 to 49.1] [p = 0.01],
      respectively). At three months, the early mobilization group had significantly
      reduced pain compared with the conventional-treatment group (between-group
      difference, 15.7 [95% confidence interval, 0.52 to 30.8] [p = 0.04]). No
      complications in displacement or nonhealing were noted. CONCLUSIONS: Early
      mobilization for impacted nonoperatively treated proximal humeral fractures is
      safe and is more effective for quickly restoring the physical capability and
      performance of the injured arm than is conventional immobilization followed by
      physiotherapy.

PMID- 18056489
TI  - Anterior transposition compared with simple decompression for treatment of
      cubital tunnel syndrome. A meta-analysis of randomized, controlled trials.
AB  - BACKGROUND: There is currently no consensus on the optimal operative treatment
      for cubital tunnel syndrome. The objective of this meta-analysis of randomized,
      controlled trials was to evaluate the efficacy of simple decompression compared
      with that of anterior transposition of the ulnar nerve in the treatment of this
      condition. METHODS: Multiple databases were searched for randomized, controlled
      trials on the outcome of operative treatment of cubital tunnel syndrome in
      patients who had not previously sustained trauma or undergone a surgical
      procedure involving the elbow. Two reviewers abstracted baseline characteristics,
      clinical scores, and motor nerve-conduction velocities independently. Data were
      pooled across studies, standard mean differences in effect sizes weighted by
      study sample size were calculated, and heterogeneity across studies was assessed.
      RESULTS: We identified four randomized, controlled trials comparing simple
      decompression with anterior ulnar nerve transposition (two submuscular and two
      subcutaneous). In three studies that included a total of 261 patients, a clinical
      scoring system was used as the primary clinical outcome. There were no
      significant differences between simple decompression and anterior transposition
      in terms of the clinical scores in those studies (standard mean difference in
      effect size = -0.04 [95% confidence interval = -0.36 to 0.28], p = 0.81). We did
      not find significant heterogeneity across these studies (I(2) = 34.2%, p = 0.22).
      Two reports, on a total of 100 patients, presented postoperative motor nerve
      conduction velocities; they showed no significant differences between the
      procedures (standard mean difference in effect size = 0.24 [95% confidence
      interval -0.15 to 0.63] in favor of simple decompression, p = 0.23; I(2) = 0%, p
      = 0.9). CONCLUSIONS: The results of this meta-analysis suggest that there is no
      difference in motor nerve-conduction velocities or clinical outcome scores
      between simple decompression and ulnar nerve transposition for the treatment of
      ulnar nerve compression at the elbow in patients with no prior traumatic injuries
      or surgical procedures involving the affected elbow. Confidence intervals around
      the points of estimate were narrow, which probably exclude the possibility of
      clinically meaningful differences. These data suggest that simple decompression
      of the ulnar nerve is a reasonable alternative to anterior transposition for the
      surgical management of ulnar nerve compression at the elbow.

PMID- 18056490
TI  - Femoral nerve block for diaphyseal and distal femoral fractures in the emergency
      department.
AB  - BACKGROUND: Diaphyseal and distal femoral fractures are painful injuries that are
      frequently seen in patients requiring a trauma work-up in the hospital emergency
      department prior to definitive management. The purpose of this study was to
      determine whether a femoral nerve block administered in the emergency department
      could provide better pain relief for patients with femoral fractures than
      currently used pain management practices. METHODS: Patients who presented with an
      acute diaphyseal or distal femoral fracture were identified as potential
      candidates for this study. Eligible patients were randomized by medical record
      number to receive either (a) the femoral nerve block (20 mL of 0.5% bupivacaine)
      along with standard pain management or (b) standard pain management alone
      (typically intravenous narcotics). The pain was assessed with use of a visual
      analog scale at the initial evaluation and at five, fifteen, thirty, sixty, and
      ninety minutes following the initial evaluation. Fifty-four patients were
      enrolled in the study from April 2005 to May 2006. Thirty-one patients received a
      femoral nerve block, and twenty-three patients received standard pain management
      alone. RESULTS: Baseline scores on the visual analog pain scale did not differ
      between the groups at the initial evaluation. The patients who received a femoral
      nerve block (along with standard pain management) had significantly lower pain
      scores at five, fifteen, thirty, sixty, and ninety minutes following the block
      than did the patients who received standard pain management alone (p < 0.001).
      The score on the visual analog pain scale across these time-points was an average
      of 3.6 points less (on a 10-point scale) for those who received the block. There
      were no infections, paresthesias, or other complications related to the femoral
      nerve block. CONCLUSIONS: The acute pain of a diaphyseal or distal femoral
      fracture can be significantly decreased through the use of a femoral nerve block
      which can be administered safely in the hospital emergency department.

PMID- 18056491
TI  - Corticosteroid injection in diabetic patients with trigger finger. A prospective,
      randomized, controlled double-blinded study.
AB  - BACKGROUND: It is generally accepted that the initial treatment for trigger
      finger is injection of corticosteroid into the flexor tendon sheath. In this
      study, the efficacy of corticosteroid injections for the treatment of trigger
      finger in patients with diabetes mellitus was evaluated in a prospective,
      randomized, controlled, double-blinded fashion and the efficacy in nondiabetic
      patients was evaluated in a prospective, unblinded fashion. METHODS: Thirty
      diabetic patients (thirty-five digits) and twenty-nine nondiabetic patients
      (twenty-nine digits) were enrolled. The nondiabetic patients were given
      corticosteroid injections in an unblinded manner. The cohort with diabetes was
      randomized into a corticosteroid group (twenty digits) or a placebo group
      (fifteen digits). Both of these groups were double-blinded. Additional
      injections, surgical intervention, and recurrent symptoms of trigger finger were
      recorded. Treatment success was defined as complete or nearly complete resolution
      of trigger finger symptoms such that surgical intervention was not required.
      RESULTS: After one or two injections, twenty-five of the twenty-nine digits in
      the nondiabetic group had a successful outcome compared with twelve of the
      nineteen in the diabetic corticosteroid group (p = 0.03) and eight of the fifteen
      in the diabetic placebo group (p = 0.006). With the numbers studied, no
      significant difference was found between the diabetic groups. Surgery was
      performed in three of the twenty-nine digits in the nondiabetic group compared
      with seven of the nineteen in the diabetic corticosteroid group and six of the
      fifteen in the diabetic placebo group. There was a significant difference in the
      prevalence of surgery between the nondiabetic group and both the diabetic
      corticosteroid group and the diabetic placebo group (p = 0.035 and p = 0.020,
      respectively). With the numbers studied, no difference was found between the
      diabetic groups with regard to the persistence of symptoms. Nephropathy and
      neuropathy were significantly associated with the need for surgery (p = 0.008 and
      p = 0.03, respectively). CONCLUSIONS: Corticosteroid injections were
      significantly more effective in the digits of nondiabetic patients than in those
      of diabetic patients. In patients with diabetes, corticosteroid injections did
      not decrease the surgery rate or improve symptom relief compared with the
      placebo. The use of corticosteroid injections for the treatment of trigger finger
      may be less effective in patients with systemic manifestations of diabetes
      mellitus.

PMID- 18056492
TI  - Revision total hip arthroplasty in octogenarians. A case-control study.
AB  - BACKGROUND: Revision total hip arthroplasty in the very elderly is believed to be
      associated with a high complication rate. We evaluated the early outcomes and
      prevalence of complications following revision total hip arthroplasty in patients
      older than eighty years of age and compared them with those in a younger patient
      population. METHODS: We retrospectively reviewed the results of 170 revision
      total hip arthroplasties that had been performed in 159 octogenarians in our
      institute between 1992 and 1999. The mean patient age at the time of surgery was
      83.8 years, and the mean follow-up time was 6.8 years. We then compared these
      results with those of 170 revision total hip arthroplasties, done with the same
      surgical technique and prosthesis, in 162 patients who were seventy years old or
      younger and followed for a mean of six years. The functional outcome and the
      quality of life following the arthroplasties were assessed with use of the Harris
      hip score and the Short Form-36 (SF-36), respectively. Risk factors for
      complications and mortality were identified, and Kaplan-Meier analysis was used
      to determine survivorship. RESULTS: The octogenarians had a significant
      improvement in the mean Harris hip score, from 47 points preoperatively to 85
      points at the time of the latest follow-up. In the control group, the Harris hip
      score also improved significantly, from a preoperative mean of 44.3 points to a
      mean of 87.9 points at the time of the latest follow-up. There was no significant
      difference between the two groups in the magnitude of improvement of the Harris
      hip score. There were 100 deaths (a rate of 58.8%) at a mean of 5.3 years
      postoperatively in the octogenarian group compared with twelve deaths (7.1%) in
      the control group (p < 0.0001). There were no intraoperative deaths in either
      group. Of the 100 octogenarian patients who died, 94% had a well-functioning hip
      at the time of death. Perioperative medical complications developed in thirty
      patients (thirty-eight hips [22.4%]) in the octogenarian group and in twenty-five
      patients (twenty-six hips [15.3%]) in the control group (p > 0.05). There were
      thirteen repeat revisions and four other types of reoperations in the
      octogenarian group and twenty-three repeat revisions and six other types of
      reoperations in the control group (p = 0.08). A dislocation was sustained by four
      patients in the octogenarian group and sixteen patients in the control group (p =
      0.01). CONCLUSIONS: Revision total hip arthroplasty can provide substantial
      clinical benefit to patients over eighty years of age. The medical complication
      rate for octogenarians may not differ significantly from that for patients
      seventy years of age or younger, and the prevalence of technical complications
      and dislocations can be expected to be lower than that for younger patients.

PMID- 18056493
TI  - Outcomes following plate fixation of fractures of both bones of the forearm in
      adults.
AB  - BACKGROUND: Internal fixation of diaphyseal forearm fractures has been associated
      with high union rates and satisfactory forearm motion. The purpose of this study
      was to investigate patient-based functional outcomes and to objectively measure
      strength following plate fixation of fractures of both bones of the forearm.
      METHODS: Range of motion, quantitative strength measurements, and validated
      outcome measures-i.e., DASH (Disabilities of the Arm, Shoulder and Hand) and SF
      36 (Short Form-36) scores-were assessed in a cohort of thirty patients (nineteen
      men and eleven women with a mean age of 43.9 years) treated with plate fixation
      for fractures of both bones of the forearm. The mean duration of follow-up was
      5.4 years, and standardized radiographs of the forearm were evaluated. Univariate
      and multivariate analyses were performed to identify determinants of the DASH and
      SF-36 Physical and Mental Component Summary (PCS and MCS) scores. RESULTS:
      Compared with the uninjured arms, the injured arms had reduced strength of
      forearm pronation (70% of that of the normal arm, p < 0.0001), forearm supination
      (68%, p < 0.0001), wrist flexion (84%, p = 0.0011), wrist extension (63%, p <
      0.0001), and grip (75%, p < 0.0001). In addition, the injured arms had a
      significantly reduced active range of forearm supination (90% of that of the
      uninjured arm, p = 0.0001), forearm pronation (91%, p = 0.0028), and wrist
      flexion (82%, p < 0.0001). The mean DASH score (18.6 points; range, 0 to 61
      points) was significantly higher than the normative value in the United States (p
      = 0.02). Limitations in strength correlated with worse DASH and SF-36 PCS scores.
      Pain and a work-related injury were independent determinants of the DASH score.
      CONCLUSIONS: Stabilization with internal plate fixation following fracture of
      both bones of the forearm restores nearly normal anatomy and motion. However, a
      moderate reduction in the strength of the forearm, the wrist, and grip should be
      expected following this injury. Perceived disability as measured with the DASH
      and SF-36 questionnaires is determined by pain more than by objective physical
      impairment.

PMID- 18056494
TI  - The influence of insurance status on the transfer of femoral fracture patients to
      a level-I trauma center.
AB  - BACKGROUND: The aim of the present study was to evaluate transfer patterns and
      insurance status for patients with a femoral fracture who were definitively
      managed within a six-hospital health-care system. We hypothesized that insurance
      status significantly influenced transfer of these patients to the level-I trauma
      center and that the level-I center provided definitive care for a
      disproportionate percentage of uninsured femoral fracture patients. METHODS: The
      present retrospective cohort study was performed within a six-hospital health
      care system. The system comprises a single American College of Surgeons
      designated level-I trauma center and five nondesignated community hospitals. We
      identified 243 patients with 251 femoral shaft fractures that had been
      definitively treated with intramedullary nail fixation within the system. From
      the health-care system billing database and trauma registries, we obtained
      diagnosis and procedure codes, insurance status, and trauma center transfer data.
      Differences in the proportions of uninsured and insured patients were calculated.
      RESULTS: One hundred and seventy-two (71%) of the 243 patients who were
      definitively managed within our health-care system initially had been taken to
      the regional level-I center, and thirty-eight patients (16%) had been transferred
      to the trauma center. Of the thirty-eight patients who had been transferred,
      eighteen (47%) had met appropriate transfer criteria. Of the twenty patients with
      an isolated femoral fracture who had been transferred from hospitals with regular
      orthopaedic coverage, four (20%) had met appropriate transfer criteria. Twenty
      two (58%) of the thirty-eight patients who had been transferred were uninsured,
      and all thirty-three patients who had not been transferred were insured (p =
      0.0008); this observation remained when controlling for injury severity and
      available orthopaedic coverage (p < 0.0001). The proportion of insured patients
      definitively managed at the trauma center (52%) differed significantly from the
      proportion of insured patients definitively managed at the community hospitals
      (100%) (p < 0.0001). CONCLUSIONS: The majority (71%) of the patients with a
      femoral fracture who had been managed definitively within our health-care system,
      regardless of injury severity, had been taken directly to the trauma center. This
      finding suggests over-triage, which errs on the side of patient well-being.
      Because there was a significant difference in insurance status between patients
      who had been transferred to the level-I center and those who had not been
      transferred as well as between patients who had been definitively managed at the
      level-I center and those who had been managed in community hospitals, it can be
      assumed that insurance status as well as injury severity and orthopaedic surgeon
      availability influence the decision to transfer femoral fracture patients to a
      level-I trauma center.

PMID- 18056495
TI  - Transphyseal anterior cruciate ligament reconstruction in skeletally immature
      pubescent adolescents.
AB  - BACKGROUND: Management of anterior cruciate ligament injuries in skeletally
      immature patients is controversial. Conventional surgical reconstruction
      techniques for adults can cause iatrogenic growth disturbance due to physeal
      damage in children. The purpose of this study was to evaluate the results of a
      transphyseal reconstruction technique in pubescent but skeletally immature
      adolescents. METHODS: Between 1996 and 2004, sixty-one knees in fifty-nine
      skeletally immature pubescent adolescents (Tanner stage 3) with a mean
      chronological age of 14.7 years (range, 11.6 to 16.9 years) underwent
      transphyseal reconstruction of the anterior cruciate ligament with use of an
      autogenous quadrupled hamstrings-tendon graft and metaphyseal fixation. Thirty
      one knees had additional meniscal surgery. The functional outcome, graft
      survival, radiographic outcome, and any growth disturbance were evaluated at a
      mean of 3.6 years (range, 2.0 to 10.2 years) after the surgery. RESULTS: Two
      patients (3%) underwent revision anterior cruciate ligament reconstruction
      because of graft failure at fourteen and twenty-one months postoperatively. For
      the remaining fifty-nine knees, the mean International Knee Documentation
      Committee subjective knee score (and standard deviation) was 89.5 +/- 10.2 points
      and the mean Lysholm knee score was 91.2 +/- 10.7 points. The result of the
      Lachman examination was normal in fifty-one knees and nearly normal in eight; it
      was not abnormal or severely abnormal in any knee. The result of the pivot-shift
      examination was normal in fifty-six knees and nearly normal in three knees; it
      also was not abnormal or severely abnormal in any knee. The mean increase in
      total height was 8.2 cm (range, 1.2 to 25.4 cm) from the time of surgery to the
      time of final follow-up. No angular deformities of the lower extremity were
      measured radiographically, and no lower-extremity length discrepancies were
      measured clinically. Complications included three cases of arthrofibrosis
      requiring manipulation with the patient under anesthesia. CONCLUSIONS:
      Transphyseal reconstruction of the anterior cruciate ligament with use of an
      autogenous quadrupled hamstrings-tendon graft with metaphyseal fixation in
      skeletally immature pubescent adolescents provides an excellent functional
      outcome with a low revision rate and a minimal risk of growth disturbance.

PMID- 18056496
TI  - Use of structural allograft in revision total knee arthroplasty in knees with
      severe tibial bone loss.
AB  - BACKGROUND: Tibial bone loss is frequently encountered at the time of revision
      total knee arthroplasty, and the outcome of the revision often depends on the
      management of this bone deficiency. We examined the clinical and radiographic
      outcomes of a series of revision total knee arthroplasties in which a structural
      allograft had been used to reconstruct a tibial bone defect encountered at the
      time of the revision procedure. METHODS: From January 1985 through September
      1999, one surgeon performed revision arthroplasty in forty-nine knees (forty
      seven patients) with a severe tibial bone defect. The reasons for the revisions
      included polyethylene wear and osteolysis in twenty-four knees, aseptic loosening
      in seventeen knees, infection in five knees, and failure for another reason for
      three knees. Structural allograft was used alone in thirty-five knees and in
      conjunction with a tibial augment in fourteen knees. The mean age of the patients
      at the time of the revision arthroplasty with the allograft was sixty-seven
      years. The patients were assessed clinically with use of the Knee Society score
      and radiographically. RESULTS: The status of the implant was known for forty-six
      of the forty-nine knees in this study. It was unknown for one patient (one knee)
      who was lost to follow-up and for two patients (two knees) who died less than
      five years postoperatively. Four revision procedures in four patients failed and
      required a reoperation. Two of the failures were due to infection. At a mean of
      ninety-seven months postoperatively, the mean Knee Society clinical score was 84
      points for the knees that had not had a reoperation due to failure. The mean arc
      of motion improved from 87 degrees preoperatively to 103 degrees at the most
      recent follow-up evaluation. Histological evaluation of specimens retrieved at
      two autopsies demonstrated graft union to host bone. CONCLUSIONS: A structural
      allograft provides a stable and durable reconstruction of a tibial bone
      deficiency. At a mean of ninety-five months postoperatively, we found no instance
      of graft collapse or aseptic loosening associated with the structural allograft.
      We recommend the use of a structural allograft for the management of severe
      tibial bone deficiency at the time of revision total knee arthroplasty.

PMID- 18056498
TI  - Mortality after periprosthetic fracture of the femur.
AB  - BACKGROUND: Management of periprosthetic femoral fractures is often complex, and
      few studies have documented its associated mortality. METHODS: We retrospectively
      identified from our trauma and surgical registries 106 patients who underwent
      surgery for a periprosthetic femoral fracture. We then identified a
      contemporaneous age and sex-matched control cohort of 309 patients who had a hip
      fracture (femoral neck or intertrochanteric) and 311 patients who underwent
      primary hip or knee replacement. Mortality at one year was identified with use of
      the Social Security database. RESULTS: Twelve (11%) of 106 patients died within
      one year following surgical treatment of a periprosthetic fracture. During the
      same follow-up period, fifty-one (16.5%) of 309 patients died following surgery
      for a hip fracture and nine (2.9%) of 311 patients died following primary joint
      replacement. The mortality rate after a periprosthetic femoral fracture was
      significantly higher (p < 0.0001) compared with that for matched patients who had
      undergone primary joint replacement, and it was similar to the mortality rate
      after a hip fracture. For periprosthetic fractures, a delay of greater than two
      days from admission to the time of surgery was associated with an increased
      mortality rate at one year (p < 0.0007). Forty-nine patients underwent revision
      arthroplasty for the treatment of a Vancouver type-B periprosthetic fracture, and
      six (12%) died. In contrast, twenty-four patients with a Vancouver type-B
      periprosthetic fracture were treated with open reduction and internal fixation
      and eight (33%) died. The difference was significant (p < 0.03). CONCLUSIONS: The
      mortality rate within one year following surgical treatment of periprosthetic
      femoral fractures is high and is similar to that after treatment for hip
      fractures. Because revision arthroplasty for the treatment of type-B
      periprosthetic fractures was associated with a one-year mortality rate that was
      significantly less than that after surgical treatment with open reduction and
      internal fixation, in instances when either treatment option is feasible,
      revision arthroplasty may be the preferred option.

PMID- 18056497
TI  - Multimodal thromboprophylaxis for total hip and knee arthroplasty based on risk
      assessment.
AB  - BACKGROUND: Orthopaedic surgeons are increasingly challenged to find a
      prophylaxis regimen that protects patients from thromboembolism while minimizing
      adverse clinical outcomes such as bleeding. We used a multimodal approach in
      which the treatment regimen is selected according to patient risk factors.
      METHODS: We retrospectively reviewed the records on 1179 consecutive total joint
      arthroplasties in 970 patients who had undergone primary and revision total hip
      and total knee replacement. Preoperatively, patients were assigned to one of two
      deep venous thrombosis prophylactic regimens on the basis of an assessment of
      their risk factors. Eight hundred and fifty-six patients (1046 operations) were
      considered to be low risk and were managed with aspirin, dipyridamole, or
      clopidogrel bisulfate as well as intermittent pneumatic calf compression devices.
      One hundred and fourteen patients (133 operations) were considered to be high
      risk and were managed with low-molecular-weight heparin or warfarin and
      intermittent calf compression. All patients were mobilized from bed within twenty
      four hours after surgery, and all underwent Doppler ultrasonography within the
      twenty-four hours before hospital discharge. All of the patients were followed
      for six months postoperatively. The prevalence of asymptomatic and symptomatic
      distal and proximal deep venous thrombosis, symptomatic and fatal pulmonary
      emboli, overall mortality, and bleeding complications was determined. Thrombotic
      events were expressed as a percentage of 1179 operations because some patients
      had two or more operations. RESULTS: Overall, there were no fatal pulmonary
      emboli, three symptomatic pulmonary emboli (prevalence, 0.25%), and five
      clinically symptomatic deep venous thrombi (0.4%). Sixty-one asymptomatic deep
      venous thrombi (5.2%) were found with use of routine postoperative Doppler
      ultrasound scans. There were three deaths (prevalence, 0.25%) that were unrelated
      to thromboembolism, and there were two nonfatal gastrointestinal bleeding events
      (prevalence, 0.17%). Wound hematomas occurred in association with five (0.4%) of
      the 1179 operations. Three nonfatal pulmonary emboli (prevalence, 0.3%) were
      detected in association with the 1046 procedures in the low-risk group, and none
      were detected in association with the 133 operations in the high-risk group (p =
      0.767). Clinically symptomatic deep venous thrombosis was detected in association
      with four (0.38%) of the 1046 operations in the low-risk group and one (0.75%) of
      the 133 operations in the high-risk group (p = 0.93). Asymptomatic distal deep
      venous thrombosis was detected in association with thirty-seven (3.5%) of the
      1046 procedures in the low-risk group and four (3.0%) of the 133 operations in
      the high-risk group. Asymptomatic proximal thrombosis was detected in association
      with fourteen (1.3%) of the 1046 procedures in the low-risk group and six (4.5%)
      of the 133 procedures in the high-risk group (p = 0.03). Wound hematomas occurred
      only in patients being managed with warfarin or low-modular-weight heparin (p =
      0.0001). CONCLUSIONS: A multimodal thromboembolic prophylactic regimen is
      consistent with protecting patients while limiting adverse clinical outcomes
      secondary to thromboembolic, vascular, and bleeding complications.

PMID- 18056499
TI  - Natural history of thoracic insufficiency syndrome: a spondylothoracic dysplasia
      perspective.
AB  - BACKGROUND: Spondylothoracic dysplasia is a condition in which bilateral chest
      wall deformity due to costovertebral rib fusion with shortening of the thoracic
      spine results in severe thoracic insufficiency syndrome and early death. Little
      is known about the long-term respiratory natural history of this disorder and the
      specific anatomic deformity. METHODS: We conducted a multicenter prospective and
      retrospective study of patients with spondylothoracic dysplasia. Medical
      evaluations, respiratory history, physical examination findings, radiographs,
      computed tomographic scans, and pulmonary function tests were studied. Anatomic,
      radiographic, and functional parameters for the disorder were established to
      determine the natural history of the thoracic insufficiency syndrome. RESULTS:
      Twenty-eight patients were identified. Eight patients had died in the neonatal
      period, and twenty were evaluated (eleven prospectively and nine
      retrospectively). The survivors were doing well clinically, but the average
      spirometric values were 27.9% of the predicted normal value for the forced vital
      capacity (FVC), 29.5% of the predicted normal value for the forced expiratory
      volume in the first second (FEV1), and 0.92 for the FEV1/FVC ratio, demonstrating
      a severe restrictive respiratory pattern. The computed tomographic scan lung
      volumes were an average of 28% of the expected values for age and gender. The
      thorax was stiff from rib fusion and was severely shortened posteriorly,
      averaging 24.2% of the predicted normal length. The thoracic spine was
      predominantly composed of block vertebrae, whereas in the lumbar region there
      were multiple hemivertebrae. Minimal scoliosis was seen, and there were no
      neurological deficits. CONCLUSIONS: Spondylothoracic dysplasia has a unique
      pathoanatomy of volume depletion deformity of the thorax with chest wall
      stiffness, resulting in thoracic insufficiency syndrome. Clinical tolerance of
      the restrictive lung disease in this disorder is impressive, but no clear reason
      has yet been identified for the clinical pulmonary health in the face of severe
      restrictive lung disease. Patients who survive infancy show no progression of
      congenital anomalies and can have a good quality of life. This disease may serve
      as a model of the natural history of thoracic insufficiency syndrome due to
      growth inhibition of the thoracic spine either as a result of congenital causes
      or secondary to surgical fusion early in life.

PMID- 18056500
TI  - Third-generation alumina-on-alumina ceramic bearings in cementless total hip
      arthroplasty.
AB  - BACKGROUND: Wear debris has been implicated in the pathogenesis of osteolysis.
      Alumina-on-alumina ceramic bearings have a low wear rate, which may reduce the
      prevalence of osteolysis. The purpose of this study was to determine the rates of
      wear and osteolysis associated with modern cementless hip arthroplasty with
      alumina-on-alumina bearings at five years. METHODS: We analyzed a series of 301
      third-generation alumina-on-alumina cementless primary total hip replacements in
      283 patients. The average age of the patients at the time of the arthroplasty was
      fifty-eight years. All procedures were performed with use of the same surgical
      technique and the same implant at a single center. At a minimum of five years
      postoperatively, ten patients had died and twenty-two patients were lost to
      follow-up. We assessed patients clinically and radiographically, and all
      retrieved bearings were analyzed for wear. RESULTS: At the time of the latest
      follow-up, the mean Harris hip score was 95 points. All surviving implants had
      radiographic evidence of stable bone ingrowth. There were nine revisions of one
      or both components. Four stems were revised following periprosthetic fracture,
      one stem was revised because of aseptic loosening at two months, and one stem was
      revised to facilitate a femoral shortening osteotomy. Two cups were revised
      because of psoas tendinitis, and both components of one arthroplasty were revised
      because of impingement and osteolysis. The rate of survival of both components,
      with revision because of aseptic loosening or osteolysis as the end point, was
      99% at seven years. The retrieved femoral heads showed an early median wear rate
      of 0.2 mm(3) per year. CONCLUSIONS: Cementless primary total hip prostheses with
      a third-generation alumina-on-alumina bearing showed very low wear and were
      associated with minimal osteolysis at the time of follow-up, at a minimum of five
      years.

PMID- 18056501
TI  - Are surgeons' preferences for instrumentation related to patient outcomes? A
      randomized clinical trial of two implants for idiopathic scoliosis.
AB  - BACKGROUND: Although many techniques for the surgical treatment of scoliosis have
      been described, we are not aware of any randomized trials that have compared
      implant systems. The relationship between surgeons' preferences for implants and
      patient outcomes is unknown. The purpose of the present study was to compare
      quality of life and curve correction associated with use of the Moss Miami system
      and the Universal Spine System for spinal fusion in patients with adolescent
      idiopathic scoliosis. METHODS: The present study was a double-blind, randomized
      clinical trial. All adolescent patients with idiopathic scoliosis who were
      scheduled for posterior instrumentation and arthrodesis with or without anterior
      release were screened for eligibility. Patients were randomly allocated to
      treatment with either the Moss Miami system or the Universal Spine System. The
      primary outcome measure for this trial was Quality of Life Profile for Spinal
      Disorders. RESULTS: Of the 129 subjects who were enrolled in the trial, sixty
      (95%) of sixty-three from the Universal Spine System group and sixty (91%) of
      sixty-six from the Moss Miami group were included in the final analysis. Two
      years postoperatively, the total Quality of Life score did not differ by the
      clinically important value of 5.5 between the two groups (difference, 1.07; 95%
      confidence interval, -3.67 to 5.82; p = 0.66). The percentage of Cobb angle
      correction was not significantly different for thoracic curves (55.1% +/- 18.3%
      for the Moss Miami system group, compared with 54.1% +/- 18.7% for the Universal
      Spine System group) (difference, -1%; 95% confidence interval, -7% to 5%; p =
      0.77) or lumbar curves (45.4% +/- 24.6% for the Moss Miami system group, compared
      with 41.9% +/- 26.8% for the Universal Spine System group) (difference, -4%; 95%
      confidence interval, -16% to 11%; p = 0.57). Although surgeons were more
      satisfied with the Universal Spine System (difference, 42%; 95% confidence
      interval, 29% to 55%; p < 0.0001), satisfaction ratings were not related to any
      surgical outcomes. CONCLUSIONS: The Moss Miami system and the Universal Spine
      Systems provided similar quality of life and curve correction. Surgeon preference
      may be an unreliable means of selecting implants from the patient outcomes
      perspective.

PMID- 18056502
TI  - Radial head dislocation and subluxation in osteogenesis imperfecta.
AB  - BACKGROUND: Upper limb deformity in children with osteogenesis imperfecta may
      substantially impair function. The aims of this retrospective work were to study
      the prevalence of radial head malalignment (dislocation or subluxation) in
      different types of osteogenesis imperfecta and to identify factors linked to it.
      METHODS: We assessed 489 upper limbs from 254 patients (with a mean age of 9.6
      years and including 130 female patients) who had various types of osteogenesis
      imperfecta. Radiographs representing a single time-point for each patient were
      assessed for the presence and direction of radial head malalignment and
      associated abnormalities (dysplasia of the capitellum or of the radial head or
      neck, calcification of the interosseous membrane, or radioulnar synostosis).
      Deformations of the humerus, radius, and ulna were assessed with regard to
      location, direction, and magnitude. The forearm range of motion in pronation and
      supination and the hand grip force were measured in a subset of patients.
      RESULTS: We observed radial head dislocation or subluxation in forty-four and
      thirty-nine upper extremities, respectively. The frequency of radial head
      malalignment was significantly higher in type-V osteogenesis imperfecta (86%)
      than in the other types (0% to 29%) (p < 0.001). Dysplasia of the humeral
      capitellum, radial head, or radial neck was associated with malalignment in all
      types of osteogenesis imperfecta, with the exception of capitellum dysplasia in
      type V. Malalignment in type V was associated with calcification of the
      interosseous membrane, an abnormality that was specific for type V. In the other
      osteogenesis imperfecta types, malalignment was commonly linked with radial and
      ulnar deformation and was associated with decreased forearm range of motion in
      supination and pronation and a lower grip force. CONCLUSIONS: Radial head
      malalignment is common in osteogenesis imperfecta, especially in type V.
      Malalignment is associated with bowing characteristics and impaired function of
      the upper limb. These findings may provide support for surgical correction of
      radial and ulnar bowing in selected patients with osteogenesis imperfecta.

PMID- 18056503
TI  - Metal-on-metal hip resurfacing for obese patients.
AB  - BACKGROUND: The effect of obesity on the outcomes of metal-on-metal resurfacing
      arthroplasty is not currently known. In this study, we assessed the influence of
      body mass index on the survival of a metal-on-metal hybrid hip resurfacing
      prosthesis by comparing the clinical results of patients with a body mass index
      of >or=30 with those of patients with a body mass index of <30. METHODS: We
      retrospectively reviewed our registry to identify all patients who had been
      followed for at least two years after a metal-on-metal hip resurfacing
      arthroplasty, and we divided those patients according to whether they had had a
      body mass index of >or=30 (the study group) or <30 (the control group) at the
      time of the surgery. One hundred and twenty-five patients (144 hips) with an
      average weight of 104.6 kg and an average body mass index of 33.4 were included
      in the study group, and 531 patients (626 hips) with an average weight of 78.3 kg
      and an average body mass index of 25.4 were included in the control group. We
      compared the clinical results (UCLA [University of California at Los Angeles] and
      Harris hip scores, SF-12 [Short Form-12] survey results, and complication rates),
      radiographic results, and prosthetic survival rates of the two groups. RESULTS:
      There was no significant difference postoperatively between the groups with
      regard to the UCLA pain or walking scores or the mental component score of the SF
      12. However, the UCLA function and activity scores were lower in the study group
      than in the control group (9.2 compared with 9.6 points [p = 0.001] and 7.1
      compared with 7.6 points [p = 0.002], respectively). The control group had a
      significantly higher postoperative physical component score on the SF-12 (51.4
      points compared with 49.3 points in the study group, p = 0.01) and postoperative
      Harris hip score (93.8 compared with 90.6 points, p = 0.0003). Two hips (1.4%)
      were revised in the study group. In contrast, thirty-one hips (5.0%) were
      converted to a total hip replacement in the control group; twenty of the thirty
      one were revised because of loosening of the femoral component. The five-year
      survivorship of the hip prostheses was 98.6% in the study group and 93.6% in the
      control group (p = 0.0401). When the entire cohort was divided into three groups
      according to whether the body mass index was <25, 25 to 29, or >or=30, the risk
      of revision was found to have decreased twofold from one group to the next as the
      body mass index increased (p = 0.013). No acetabular component loosened in either
      group. The average diameter of the femoral component was 48.3 mm in the study
      group and 46.8 mm in the control group (p = 0.0001). There were no revisions for
      any reason and no radiolucencies were observed in a subset of twenty-seven
      patients with a body mass index of >or=35. CONCLUSIONS: Metal-on-metal
      resurfacing hip arthroplasty is performing well in patients with a high body mass
      index, although the function scores are reduced compared with those for patients
      with a body mass index of <30. The protective effect of a high body mass index on
      survivorship results may be explained by a reduced activity level and a greater
      component size in this patient population.

PMID- 18056504
TI  - Legg-calve-perthes disease: a review of cases with onset before six years of age.
AB  - BACKGROUND: The prognosis for children in whom Legg-Calve-Perthes disease
      develops before the age of six years was initially reported to be good, but later
      studies demonstrated a less favorable prognosis. To assess the natural history of
      this condition in this age group, we reviewed a large cohort of children who had
      received minimal treatment for the disease. METHODS: The medical records and
      radiographs of all children with Legg-Calve-Perthes disease seen at our
      institution between 1944 and 2000 were reviewed. The cases of 172 patients with a
      total of 188 affected hips were studied. The course of the disease and the final
      clinical and radiographic outcomes were evaluated in all patients. RESULTS:
      Typical Legg-Calve-Perthes disease was noted in 164 hips of 160 patients.
      According to the lateral patellar classification, seven of these hips were in
      group A; 101, in group B; twenty-seven, in the B/C border group; and twenty-nine,
      in group C. According to the Stulberg classification, there were 131 Class-I or
      II (good) results, fourteen Class-III (fair) results, and nineteen Class-IV
      (poor) results. The lateral pillar classification was highly correlated with the
      outcome, whereas treatment did not correlate with the outcome. Only lateral
      pillar group-B/C border and C hips with an onset of the disease between the ages
      of four years and five years and eleven months had a poor prognosis. We
      unexpectedly encountered a group of twelve patients with bilateral, simultaneous
      development of apparent Legg-Calve-Perthes disease. In that group, there were
      twenty-one Stulberg Class-I or II (good), three Stulberg Class-III (fair), and no
      Stulberg Class-IV (poor) results, although fourteen of the twenty-four hips were
      in lateral pillar group C. The outcome in the hips in lateral pillar group C was
      significantly better when the patient had bilateral simultaneous involvement than
      when the patient had typical Legg-Calve-Perthes disease. CONCLUSIONS: The
      prognosis for patients with the onset of Legg-Calve-Perthes disease before the
      age of six years is favorable, with 80% having a good result. Only children
      between the ages of four years and five years and eleven months with a B/C or C
      lateral pillar classification of involvement have a less favorable prognosis.
      Treatment was not found to influence outcome. Simultaneous bilateral disease,
      which had a more favorable prognosis, may represent a unique disorder.

PMID- 18056505
TI  - Relationship between varus-valgus alignment and patellar kinematics in
      individuals with knee osteoarthritis.
AB  - BACKGROUND: Abnormal varus-valgus alignment is a risk factor for patellofemoral
      osteoarthritis, but tibiofemoral alignment alone does not explain compartmental
      patellofemoral osteoarthritis progression. Other mechanical factors, such as
      patellar kinematics, probably play a role in the initiation and progression of
      the disease. The objective of this study was to determine which three-dimensional
      patellar kinematic parameters (patellar flexion, spin, and tilt and patellar
      proximal, lateral, and anterior translation) are associated with varus and valgus
      alignment in subjects with osteoarthritis. METHODS: Ten individuals with knee
      osteoarthritis and varus (five subjects) or valgus (five subjects) knee alignment
      underwent assessment of three-dimensional patellar kinematics. We used a
      validated magnetic resonance imaging-based method to measure three-dimensional
      patellar kinematics in knee flexion while the subjects pushed against a pedal
      with constant load (80 N). A linear random-effects model was used to test the
      null hypothesis that there was no difference in the relationship between
      tibiofemoral flexion and patellar kinematics between the varus and valgus groups.
      RESULTS: Patellar spin was significantly different between groups (p = 0.0096),
      with the varus group having 2 degrees of constant internal spin and the valgus
      group having 4.5 degrees of constant external spin. In the varus group, the
      patellae tracked with a constant medial tilt of 9.6 degrees with flexion, which
      was significantly different (p = 0.0056) from the increasing medial tilt (at a
      rate of 1.8 degrees per 10 degrees of increasing knee flexion) in the valgus
      group. The patellae of the valgus group were 7.5 degrees more extended (p =
      0.0093) and positioned 8.8 mm more proximally (p = 0.0155) than the varus group
      through the range of flexion that was studied. The pattern of anterior
      translation differed between the groups (p = 0.0011). CONCLUSIONS: Our results
      suggest that authors of future large-scale studies of the relationships between
      knee mechanics and patellofemoral osteoarthritis should not rely solely on
      measurements of tibiofemoral alignment and should assess three-dimensional
      patellar kinematics directly.

PMID- 18056506
TI  - Crowned Dens syndrome.
AB  - BACKGROUND: Patients with crowned dens syndrome typically present with severe
      neck pain and have calcium deposits around the odontoid process of the axis on
      radiographs. To our knowledge, the cases of only thirty-five patients have been
      reported in the English-language literature and the clinical features remain
      unclear. The purposes of this study were to examine the clinical features of
      crowned dens syndrome, determine treatment outcomes, and propose diagnostic
      criteria. METHODS: Forty patients with severe neck pain had calcium deposition
      around the odontoid process on computed tomography scans, and they were thus
      diagnosed as having crowned dens syndrome. Data were collected in relation to
      these patients, including the date of onset of neck pain, the presence of
      inflammatory indicators (increased body temperature, C-reactive protein levels,
      and white blood-cell count), and treatment outcomes. RESULTS: The male-to-female
      ratio was 0.6, and two-thirds of the patients were more than seventy years of
      age. All patients had markedly restricted neck motion, particularly in rotation,
      and all had one or more positive inflammatory indicators. Calcium deposition was
      detected in all areas around the odontoid process, but chiefly behind the
      process. Pain was typically relieved by nonsteroidal anti-inflammatory drugs,
      prednisolone, or both. A combination of both appeared to be the most effective.
      CONCLUSIONS: We believe that crowned dens syndrome is more common than previously
      recognized, especially in elderly patients. It is diagnosed on the basis of acute
      and severe neck pain; marked restriction of neck motion, particularly in
      rotation; the presence of inflammatory indicators, such as an elevated C-reactive
      protein level; calcium deposition around the odontoid process detected by
      computed tomography; no history of trauma; and the exclusion of other
      inflammatory diseases and tumors. Prednisolone and nonsteroidal anti-inflammatory
      drugs in combination are the recommended treatment for symptom relief.

PMID- 18056507
TI  - Skeletal age assessment from the olecranon for idiopathic scoliosis at Risser
      grade 0.
AB  - BACKGROUND: The main progression of idiopathic scoliosis occurs during peak
      height growth velocity, which is between the ages of eleven and thirteen years in
      girls and thirteen and fifteen years in boys and corresponds to the accelerating
      phase of pubertal growth. The Risser sign remains at grade 0 during this stage of
      growth. Triradiate cartilage closure occurs at approximately twelve years of age
      in girls and fourteen years in boys, which is in the middle of this phase. In
      addition to regular height measurements, a more detailed evaluation of skeletal
      maturity would be desirable prior to the identification of Risser grade 1. From
      the method of Sauvegrain et al., Dimeglio derived a simplified method based on
      the radiographic appearance of the olecranon, which allows skeletal age to be
      assessed in six-month intervals. The purpose of this study was to determine the
      accuracy and the value of this simple method for the follow-up of patients with
      scoliosis. METHODS: Five radiographic images demonstrate the typical
      characteristics of the olecranon during pubertal growth: two ossification nuclei,
      a half-moon image, a rectangular shape, the beginning of fusion, and complete
      fusion. This classification method was evaluated by three experienced and
      independent observers from lateral radiographs of the elbow in 100 boys and 100
      girls with idiopathic scoliosis during the time of peak height velocity. Skeletal
      ages were correlated with the integral Sauvegrain method. The degree of
      interobserver concordance was determined, and skeletal age was compared with
      chronological age and the time of triradiate cartilage closure. RESULTS: For the
      three observers, the average concordance between the Sauvegrain and olecranon
      methods was excellent (r = 0.977 for boys and r = 0.938 for girls). The
      interobserver agreement was also excellent (r = 0.987 for the olecranon method
      and r = 0.958 for the Sauvegrain method for boys, and r = 0.992 and r = 0.985,
      respectively, for girls). Skeletal and chronological age were considered to
      correspond to each other within a six-month range for 49% of the boys and 51% of
      the girls, while 25% of the boys and 26% of the girls had an advanced skeletal
      age and 26% of boys and 23% of girls had a delayed skeletal age. Triradiate
      cartilage closure occurred at the same time as the appearance of the rectangular
      shape of the olecranon in 65% of the boys and 61% of the girls, corresponding to
      skeletal ages of fourteen and twelve years, respectively. In 91% of the boys and
      88% of the girls, the triradiate cartilage fused within six months before to six
      months after the appearance of the rectangular shape of the olecranon, which
      occurred between the half-moon image and the beginning of fusion of the
      olecranon. CONCLUSIONS: The method of assessing skeletal age from the olecranon
      allows skeletal maturity to be evaluated in regular six-month intervals during
      the phase of peak height velocity. This method is simple, precise, and reliable.
      It complements the Risser grade-0 and the triradiate cartilage evaluation.

PMID- 18056508
TI  - Biomechanical effects of kneeling after total knee arthroplasty.
AB  - BACKGROUND: Kneeling following total knee arthroplasty can be a difficult task,
      impairing the activities of patients to varying degrees. Little is known about
      the biomechanical effects of kneeling following total knee replacement. The
      objective of this study was to quantify the effects of kneeling on patellofemoral
      joint contact areas and pressures, knee joint reaction force, and patellar
      kinematics. METHODS: Total knee arthroplasties were performed on eight fresh
      frozen cadaveric knees, and they were tested with use of a custom knee jig, which
      permits the simulation of physiologic quadriceps loading as well as the
      application of an anterior force to simulate kneeling. The knees were tested at
      flexion angles of 90 degrees , 105 degrees , 120 degrees , and 135 degrees with
      no anterior force (mimicking a squatting position) and with an anterior force
      application simulating double-stance kneeling and single-stance kneeling.
      Patellofemoral joint contact areas and pressures were measured with pressure
      sensitive film, and the knee joint reaction force was measured with use of a six
      degree-of-freedom load cell. Patellar kinematics were assessed with use of
      digital photographs tracking fixed markers on the patella. RESULTS: Compared with
      the condition without kneeling, both single-stance and double-stance kneeling
      demonstrated significant increases in patellofemoral contact area (p < 0.05) and
      pressure at all flexion angles (p < 0.05), with the exception of double-stance
      kneeling at 135 degrees of flexion. The resultant knee joint -reaction force
      increased with kneeling at all flexion angles. The compressive component of this
      force increased with kneeling for most conditions, while the lateral component of
      this force decreased significantly (p < 0.05) with kneeling only at 90 degrees ,
      and the anterior component of this force increased significantly at all knee
      flexion angles (p < 0.05). Overall, kneeling had minimal changes on patellar
      tilt, with significant changes in patellar tilt seen only with kneeling at 120
      degrees (p = 0.02 for double stance, and p = 0.03 for single stance).
      CONCLUSIONS: The findings of this study suggest that kneeling at a higher flexion
      angle (135 degrees ) after total knee arthroplasty has a smaller effect on
      patellofemoral joint contact area and pressure than kneeling at lower flexion
      angles (<or=120 degrees ).

PMID- 18056509
TI  - Osteonecrosis of the knee treated with a tissue-engineered cartilage and bone
      implant. A case report.

PMID- 18056510
TI  - Ion production and excretion in a patient with a metal-on-metal bearing hip
      prosthesis. A case report.

PMID- 18056511
TI  - Traumatic transfemoral amputation with concomitant ipsilateral proximal femoral
      fracture. A report of two cases.

PMID- 18056512
TI  - Salvage of a below-the-knee amputation level following a type-IIIB open tibial
      fracture. A case report.

PMID- 18056513
TI  - Clinical performance of highly cross-linked polyethylenes in total hip
      arthroplasty.
AB  - Aseptic loosening secondary to wear-debris-induced osteolysis has been identified
      as the leading cause of late failure of total hip arthroplasty. Highly cross
      linked polyethylene acetabular liners were developed as one approach to reducing
      this wear. Preclinical laboratory wear testing showed a number of cross-linked
      polyethylenes to have dramatically less wear than the polyethylene that had been
      in use for several decades. After the initial bedding-in phase (one to two
      years), the percent reductions in the wear rate, as indicated by the amount of
      penetration of the head into the socket evident on serial radiographs, have been
      comparable with what was predicted from preclinical hip-simulator testing of the
      highly cross-linked polyethylenes. To our knowledge, there have been no reports
      of clinically relevant osteolysis that was clearly attributable to wear of a
      highly cross-linked polyethylene acetabular liner. However, the clinical
      performance of these materials should be closely monitored with long-term follow
      up.

PMID- 18056514
TI  - Hattage.

PMID- 18056515
TI  - AOA Symposium. Orthopaedists partnering with other physicians to provide
      musculoskeletal care.

PMID- 18056516
TI  - The effect of computer navigation on trainee learning of surgical skills.
AB  - BACKGROUND: While computer-assisted orthopaedic surgery technology may facilitate
      performance and learning in the expert, its effects on the trainee are unclear.
      Motor learning theory suggests that, while the real-time feedback provided by
      computer-assisted orthopaedic surgery should improve performance, it may be
      detrimental to learning. The purpose of this study was to assess the effects of
      computer-assisted orthopaedic surgery on the learning of surgical skills by
      trainees. METHODS: Forty-five participants were randomized to one of three
      training groups-conventional training, computer navigation, or knowledge of
      results-in which they learned technical skills related to total hip replacement.
      Outcomes were assessed in a pretest session and in ten-minute and six-week
      retention and transfer tests. RESULTS: All groups demonstrated improved accuracy
      and precision in the determination of the abduction angle and the version angle
      of the acetabular cups during training (p < 0.001). The computer navigation group
      demonstrated significantly better accuracy and precision in early training (p <
      0.05) and better precision throughout training (p < 0.05). No significant
      degradation in performance was observed between the immediate and the delayed
      testing for any group, suggesting that there was task learning in all groups with
      no negative effects of the tested training modalities on learning. CONCLUSIONS:
      In this study, the concurrent augmented feedback provided by computer-assisted
      orthopaedic surgery resulted in improved early performance and equivalent
      learning. While we did not observe a compromise in learning, further
      investigation is required to ensure that computer-assisted orthopaedic surgery
      does not compromise trainee learning in more complex tasks.

PMID- 18056520
TI  - Counterpoint: Sickle cell trait should not be considered asymptomatic and as a
      benign condition during physical activity.

PMID- 18056523
TI  - Re: Point:Counterpoint: Sickle cell trait should/should not be considered
      asymptomatic and as a benign condition during physical activity.

PMID- 18056526
TI  - Prasugrel compared with high loading- and maintenance-dose clopidogrel in
      patients with planned percutaneous coronary intervention: the Prasugrel in
      Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation
      Thrombolysis in Myocardial Infarction 44 trial.
AB  - BACKGROUND: The increasing use of higher-than-approved doses of clopidogrel in
      clinical practice is based in part on the desire for greater levels of inhibition
      of platelet aggregation (IPA). Prasugrel is a new thienopyridine that is more
      potent than standard-dose clopidogrel in healthy subjects and patients with
      stable coronary artery disease. The relative antiplatelet effects of prasugrel
      versus high-dose clopidogrel in percutaneous coronary intervention patients are
      unknown. METHODS AND RESULTS: Prasugrel in Comparison to Clopidogrel for
      Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial
      Infarction 44 (PRINCIPLE-TIMI 44) was a randomized, double-blind, 2-phase
      crossover study of prasugrel compared with high-dose clopidogrel in patients
      undergoing cardiac catheterization for planned percutaneous coronary
      intervention. The primary end point of the loading-dose phase (prasugrel 60 mg
      versus clopidogrel 600 mg) was IPA with 20 mumol/L ADP at 6 hours. Patients with
      percutaneous coronary intervention entered the maintenance-dose phase, a 28-day
      crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a
      primary end point of IPA after 14 days of either drug. In this study, 201
      subjects were randomized. IPA at 6 hours was significantly higher in subjects
      receiving prasugrel (mean+/-SD, 74.8+/-13.0%) compared with clopidogrel (31.8+/
      21.1%; P<0.0001). During the maintenance-dose phase, IPA with 20 mumol/L ADP was
      higher in subjects receiving prasugrel (61.3+/-17.8%) compared with clopidogrel
      (46.1+/-21.3%; P<0.0001). Results were consistent across all key secondary end
      points; significant differences emerged by 30 minutes and persisted across all
      time points. CONCLUSIONS: Among patients undergoing cardiac catheterization with
      planned percutaneous coronary intervention, loading with 60 mg prasugrel resulted
      in greater platelet inhibition than a 600-mg clopidogrel loading dose.
      Maintenance therapy with prasugrel 10 mg/d resulted in a greater antiplatelet
      effect than 150 mg/d clopidogrel.

PMID- 18056527
TI  - Coffee consumption and risk of cardiovascular events after acute myocardial
      infarction: results from the GISSI (Gruppo Italiano per lo Studio della
      Sopravvivenza nell'Infarto miocardico)-Prevenzione trial.
AB  - BACKGROUND: The relation between coffee consumption and cardiovascular disease
      has been studied extensively, but results are still debated. In addition, little
      evidence is available on patients with established coronary heart disease.
      METHODS AND RESULTS: Prospectively ascertained information among 11,231 Italian
      patients (9584 males and 1647 females) with recent (< or = 3 months) myocardial
      infarction enrolled in the GISSI (Gruppo Italiano per lo Studio della
      Sopravvivenza nell'Infarto miocardico)-Prevenzione trial was used. Usual dietary
      habits were assessed at baseline and updated at 0.5 and 1.5 years. Coffee
      consumption was categorized as never/almost never, < 2 cups per day, 2 to 4 cups
      per day, and > 4 cups per day. Medication use and fasting glucose were assessed
      at 0.5, 1, 1.5, 2.5, and 3.5 years. Risk was evaluated with Cox proportional
      hazards with time-varying covariates. The main outcome measure was the cumulative
      incidence of cardiovascular events (cardiovascular death, nonfatal myocardial
      infarction, and nonfatal stroke). A total of 1167 cardiovascular events occurred
      during 36,961 person-years of follow-up. After multivariable adjustment for
      potential confounders in the time-dependent analysis, the relative risk of
      cardiovascular events across categories of coffee consumption was 1.02 (95% CI
      0.87 to 1.20) for < 2 cups per day, 0.91 (95% CI 0.75 to 1.09) for 2 to 4 cups
      per day, and 0.88 (95% CI 0.64 to 1.20) for > 4 cups per day compared with
      abstainers (P for trend=0.18). Ultimately, coffee consumption did not change the
      risk of coronary heart disease events, stroke, and sudden death. CONCLUSIONS: No
      association between moderate coffee intake and cardiovascular events was observed
      in post-myocardial infarction patients.

PMID- 18056529
TI  - Exploring the behavior of hospital composite performance measures: an example
      from coronary artery bypass surgery.
AB  - BACKGROUND: Composite scores that combine several performance measures into a
      single ranking are becoming the accepted metric for assessing hospital
      performance. In particular, the Centers for Medicare & Medicaid Services Hospital
      Quality Incentive Demonstration (HQID) project bases financial rewards and
      penalties on these scores. Although the HQID composite calculation is
      straightforward and easily understood, its method of combining process and
      outcome measures has not been validated. METHODS AND RESULTS: Using data on 530
      hospitals from the Society of Thoracic Surgeons National Cardiac Database, we
      replicated the HQID methodology with 6 nationally endorsed performance measures
      (5 process measures plus survival) for coronary artery bypass surgery. Composite
      scores were essentially determined by process measure performance alone; the
      survival component explained only 4% of the composite score's total variance.
      This result persisted even when the survival component was allowed a 5-fold
      greater weighting in the composite summary. The popular "all-or-none" measurement
      approach was also dominated by the process component. Substantial disagreement
      was found among hospital rankings when several alternative methods were used; up
      to 60% of hospitals eligible for the top financial reward under HQID would change
      designation depending on the composite methodology used. The application of a
      simple statistical adjustment (standardization) to each method would provide more
      consistent results and a more balanced assessment of performance based on both
      process and outcomes. CONCLUSIONS: Existing methods used to create composite
      performance measures have remarkably different weighting of process versus
      outcomes metrics and lead to highly divergent provider rankings. Simple
      alternative methods can create more balanced process-outcome performance
      assessments.

PMID- 18056528
TI  - Rad GTPase deficiency leads to cardiac hypertrophy.
AB  - BACKGROUND: Rad (Ras associated with diabetes) GTPase is the prototypic member of
      a subfamily of Ras-related small G proteins. The aim of the present study was to
      define whether Rad plays an important role in mediating cardiac hypertrophy.
      METHODS AND RESULTS: We document for the first time that levels of Rad mRNA and
      protein were decreased significantly in human failing hearts (n=10) compared with
      normal hearts (n=3; P<0.01). Similarly, Rad expression was decreased
      significantly in cardiac hypertrophy induced by pressure overload and in cultured
      cardiomyocytes with hypertrophy induced by 10 micromol/L phenylephrine. Gain and
      loss of Rad function in cardiomyocytes significantly inhibited and increased
      phenylephrine-induced hypertrophy, respectively. In addition, activation of
      calcium-calmodulin-dependent kinase II (CaMKII), a strong inducer of cardiac
      hypertrophy, was significantly inhibited by Rad overexpression. Conversely,
      downregulation of CaMKIIdelta by RNA interference technology attenuated the
      phenylephrine-induced hypertrophic response in cardiomyocytes in which Rad was
      also knocked down. To further elucidate the potential role of Rad in vivo, we
      generated Rad-deficient mice and demonstrated that they were more susceptible to
      cardiac hypertrophy associated with increased CaMKII phosphorylation than wild
      type littermate controls. CONCLUSIONS: The present data document for the first
      time that Rad is a novel mediator that inhibits cardiac hypertrophy through the
      CaMKII pathway. The present study will have significant implications for
      understanding the mechanisms of cardiac hypertrophy and setting the basis for the
      development of new strategies for treatment of cardiac hypertrophy.

PMID- 18056530
TI  - Progesterone regulates cardiac repolarization through a nongenomic pathway: an in
      vitro patch-clamp and computational modeling study.
AB  - BACKGROUND: Female sex is an independent risk factor for torsade de pointes in
      long-QT syndrome. In women, QT interval and torsade de pointes risk fluctuate
      dynamically during the menstrual cycle and pregnancy. Accumulating clinical
      evidence suggests a role for progesterone; however, the effect of progesterone on
      cardiac repolarization remains undetermined. METHODS AND RESULTS: We investigated
      the effects of progesterone on action potential duration and membrane currents in
      isolated guinea pig ventricular myocytes. Progesterone rapidly shortened action
      potential duration, which was attributable mainly to enhancement of the slow
      delayed rectifier K+ current (I(Ks)) under basal conditions and inhibition of L
      type Ca2+ currents (I(Ca,L)) under cAMP-stimulated conditions. The effects of
      progesterone were mediated by nitric oxide released via nongenomic activation of
      endothelial nitric oxide synthase; this signal transduction likely takes place in
      the caveolae because sucrose density gradient fractionation experiments showed
      colocalization of the progesterone receptor c-Src, phosphoinositide 3-kinase,
      Akt, and endothelial nitric oxide synthase with KCNQ1, KCNE1, and Ca(V)1.2 in the
      caveolae fraction. We used computational single-cell and coupled-tissue action
      potential models incorporating the effects of progesterone on I(Ks) and I(Ca,L);
      the model reproduces the fluctuations of cardiac repolarization during the
      menstrual cycle observed in women and predicts the protective effects of
      progesterone against rhythm disturbances in congenital and drug-induced long-QT
      syndrome. CONCLUSIONS: Our data show that progesterone modulates cardiac
      repolarization by nitric oxide produced via a nongenomic pathway. A combination
      of experimental and computational analyses of progesterone effects provides a
      framework to understand complex fluctuations of QT interval and torsade de
      pointes risks in various hormonal states in women.

PMID- 18056532
TI  - Harmonising Cardiology Training Across Europe.

PMID- 18056531
TI  - Direct left atrial pressure monitoring in ambulatory heart failure patients:
      initial experience with a new permanent implantable device.
AB  - BACKGROUND: We describe the first human experience with a permanently
      implantable, direct left atrial pressure (LAP) monitoring system in ambulatory
      patients with chronic heart failure. METHODS AND RESULTS: Eight patients with
      established heart failure and at least 1 heart failure hospitalization or
      unplanned visit for parenteral therapy in the last year underwent device
      implantation under fluoroscopic guidance. All subjects received aspirin 150 mg
      and clopidogrel 75 mg daily. Subjects measured LAP twice daily and attended a
      clinic regularly for data upload and device calibration. Right heart
      catheterization was performed at the time of device implantation and at 12 weeks.
      The device was implanted in all subjects with no procedural complications. At the
      12-week follow-up, 87% of device LAP measurements were within +/-5 mm Hg of
      simultaneous pulmonary capillary wedge pressure readings over a wide range of
      pressures (1.6 to 71 mm Hg). Net drift corrected by calibration was -0.2+/-1.9 mm
      Hg/mo. During short-term follow-up, there were no device-related complications or
      systemic emboli. There were no deaths, no unplanned heart failure clinic visits,
      and no admissions for heart failure. CONCLUSIONS: Ambulatory monitoring of direct
      LAP with a new implantable device was well tolerated, feasible, and accurate at a
      short-term follow-up. Further follow-up and investigation are warranted to
      evaluate the clinical utility of LAP monitoring in patients with heart failure.

PMID- 18056533
TI  - Predominant, severe right ventricular outflow tract obstruction in hypertrophic
      cardiomyopathy.

PMID- 18056534
TI  - Letter by Ly regarding article, "Direct intramyocardial but not intracoronary
      injection of bone marrow cells induces ventricular arrhythmias in a rat chronic
      ischemic heart failure model".

PMID- 18056535
TI  - Evaluating the optimal timing of angiography: landmark or off the mark?

PMID- 18056536
TI  - Testosterone making an entry into the cardiometabolic world.

PMID- 18056537
TI  - Quantifying diastolic function in hypertrophic cardiomyopathy: the ongoing search
      for the holy grail.

PMID- 18056539
TI  - Clinical use of electrocardiography in adults with congenital heart disease.

PMID- 18056538
TI  - Sirolimus and cardiac transplantation: is it the "magic bullet"?

PMID- 18056540
TI  - The effects of biological sex and diet on the development of heart failure.

PMID- 18056541
TI  - The Water-lily pond--symphony in green.

PMID- 18056542
TI  - Substantial genetic overlap between neurocognition and schizophrenia: genetic
      modeling in twin samples.
AB  - CONTEXT: The use of endophenotypes, biological traits that increase the liability
      to a disorder, represents one strategy to facilitate the detection of
      susceptibility genes for complex behavioral disorders such as schizophrenia.
      Establishing that a candidate trait is both heritable and linked genetically to
      schizophrenia is integral to its validity as an endophenotypic marker.
      Neurocognitive deficits are among the most promising indicators of increased risk
      for schizophrenia; however, it is not clear to what extent these deficits are
      genetically linked to the disorder. OBJECTIVES: To quantify the genetic and
      environmental contributions to the variability of selected neurocognitive
      measures and to estimate the genetic relationship between these and
      schizophrenia. DESIGN: Genetic model fitting to monozygotic and dizygotic twin
      data. SETTING: United Kingdom psychiatric research institute. PARTICIPANTS: Two
      hundred sixty-seven monozygotic and dizygotic twins concordant and discordant for
      schizophrenia, and healthy monozygotic and dizygotic control twin pairs. MAIN
      OUTCOME MEASURES: The heritabilities of intelligence, working memory, processing
      speed, perceptual organization, and verbal comprehension were estimated, and the
      genetic relationship between each of these and schizophrenia was quantified.
      RESULTS: Genetic influences contributed substantially to all of the cognitive
      domains, but intelligence and working memory were the most heritable. A
      significant correlation was found between intelligence and schizophrenia (r = 
      0.61; 95% confidence interval, -0.71 to -0.48), with shared genetic variance
      accounting for 92% of the covariance between the two. Genetic influences also
      explained most of the covariance between working memory and schizophrenia.
      Significant but lesser portions of covariance between the other cognitive domains
      and schizophrenia were also found to be genetically shared. Environmental
      effects, although separately linked to neurocognition and schizophrenia, did not
      generally contribute to their covariance. CONCLUSION: Genomewide searches using
      factorial designs stratifying for levels of intelligence and working memory will
      assist in the search for finding quantitative trait loci for schizophrenia.

PMID- 18056543
TI  - Limbic activation associated with misidentification of fearful faces and flat
      affect in schizophrenia.
AB  - CONTEXT: Deficits in emotion processing are prominent in schizophrenia, and flat
      affect is resistant to treatment and portends poor outcome. Investigation of the
      underlying neural circuitry can elucidate affective dysfunction. OBJECTIVE: To
      examine the brain circuitry for facial emotion processing, dissecting response to
      task demands from effects of the appearance of facial expressions. DESIGN: A
      facial emotion identification task was presented during high-field (4-T) magnetic
      resonance imaging. Blood oxygenation level-dependent changes were contrasted for
      task compared with a scrambled face baseline (blocked analysis) and for the
      appearance of each of the following 4 target expressions compared with neutral
      faces (event related): happy, sad, anger, and fear. SETTING: Participants from
      the Schizophrenia Research Center underwent a functional magnetic resonance
      imaging study at the University of Pennsylvania Medical Center. PARTICIPANTS:
      Patients with DSM-IV-defined schizophrenia (n = 16) and healthy controls (n = 17)
      were recruited from the community. MAIN OUTCOME MEASURES: The percentage of
      signal change for each contrast and performance and clinical symptom severity
      ratings. RESULTS: Patients showed reduced limbic activation compared with
      controls for the emotion identification task. However, event-related analysis
      revealed that whereas in controls greater amygdala activation was associated with
      correct identifications of threat-related (anger and fear) expressions, patients
      showed the opposite effect of greater limbic activation, portending
      misidentifications. Furthermore, greater amygdala activation to the presentation
      of fearful faces was highly correlated with greater severity of flat affect.
      CONCLUSIONS: Abnormal amygdala activation in schizophrenia in response to
      presentation of fearful faces is paradoxically associated with failure to
      recognize the emotion and with more severe flat affect. This finding suggests
      that flat affect in schizophrenia relates to overstimulation of the limbic
      system.

PMID- 18056544
TI  - Risk of malignancy in patients with schizophrenia or bipolar disorder: nested
      case-control study.
AB  - CONTEXT: There is conflicting evidence on whether people with schizophrenia have
      a different risk of cancer from that of the general population. OBJECTIVE: To
      determine the risk of 6 common cancers in patients with schizophrenia or bipolar
      disorder. DESIGN: Population-based, nested, case-control study. SETTING: A total
      of 454 practices contributing to the QRESEARCH general practice database.
      PARTICIPANTS: We analyzed 40,441 incident cases of 6 cancers (breast, colon,
      rectal, gastroesophageal, prostate, and respiratory) and up to 5 controls per
      case matched by single year of age, sex, general practice, and calendar time.
      MAIN OUTCOME MEASURES: Odds ratios (ORs) for cancer risk associated with
      schizophrenia and bipolar disorder, adjusting for smoking, body mass index,
      socioeconomic status, comorbidities, and prescribed medications, including
      antipsychotics. RESULTS: For breast cancer, we identified 10,535/50,074
      cases/controls; colon cancer, 5108/24,458; rectal cancer, 3248/15,552;
      gastroesophageal cancer, 3854/18,477; prostate cancer, 10,190/48,748; and
      respiratory cancer, 7506/35,981. After adjustment, patients with schizophrenia
      had a 190% increased colon cancer risk (adjusted OR, 2.90; 95% confidence
      interval [CI], 1.85-4.57), a marginal increased breast cancer risk (adjusted OR,
      1.52; 95% CI, 1.10-2.11), and a 47% decreased respiratory cancer risk (adjusted
      OR, 0.53, 95% CI, 0.34-0.85). Patients with schizophrenia taking antipsychotics
      had a 308% increased colon cancer risk (adjusted OR, 4.08; 95% CI, 2.43-6.84).
      Patients with bipolar disorder had cancer risks similar to patients with neither
      condition after adjustment. CONCLUSIONS: Patients with schizophrenia have a
      significantly higher risk of colon cancer and a lower risk of respiratory cancer
      compared with patients without schizophrenia after adjustment for confounders. In
      contrast, the risks of cancer in patients with and without bipolar disorder are
      similar, suggesting that residual confounding is unlikely to explain the
      findings. The increased risk of colon cancer is particularly marked in patients
      with schizophrenia who take antipsychotic medications.

PMID- 18056545
TI  - High income, employment, postgraduate education, and marriage: a suicidal
      cocktail among psychiatric patients.
AB  - CONTEXT: Studies dating back over 100 years have shown that the risk of suicide
      in the general population is associated with low income, unemployment,
      educational underachievement, and singleness. However, little is known about the
      association between suicide risk and these factors in psychiatric patients.
      OBJECTIVE: To estimate the association between suicide risk, socioeconomic
      position, and marital status in psychiatric patients. DESIGN, SETTING, AND
      PATIENTS: Population-based cohort study of all first-ever psychiatric patients
      aged 16 to 65 years admitted from 1981 to 1998, with administrative longitudinal
      data on income, labor market affiliation, educational attainment, and marital and
      cohabitational status (96,369 patients, 256,619 admissions, and 2727 suicides).
      MAIN OUTCOME MEASURES: Suicide risks after hospital discharge were depicted using
      Kaplan-Meier product-limit methods. Hazard ratios (HRs) for suicide from Cox
      proportional hazards regression and case-crossover/individually stratified
      analyses were calculated while adjusting for overall social drift. RESULTS: Using
      Cox proportional hazards regression, compared with patients in the highest income
      quartile, the suicide HR decreased from 0.90 (95% confidence interval [CI], 0.79
      1.02) in the third lowest to 0.83 (95% CI, 0.73-0.93) in the second lowest and to
      0.68 (95% CI, 0.61-0.76) in the lowest income group. Compared with the fully
      employed, the HR for unemployed patients was 0.85 (95% CI, 0.77-0.93); for social
      benefits' recipients, 0.58 (95% CI, 0.48-0.70); and for disability or age
      pensioners, 0.63 (95% CI, 0.55-0.71). Compared with postgraduate education, HRs
      (95% CIs) associated with a bachelor's degree, vocational school, or primary
      school education were 0.82 (0.67-1.02), 0.66 (0.55-0.80), and 0.54 (0.44-0.65),
      respectively. The HRs (95% CIs) for widowed, divorced, and never-married patients
      were 1.07 (0.89-1.30), 0.74 (0.66-0.84), and 0.88 (0.79-0.98), respectively.
      Using individually stratified analyses, HRs (95% CIs) for transition into the
      third lowest, the second lowest, and the lowest income quartile were 1.19 (0.76
      1.86), 1.47 (0.92-2.34), and 1.84 (1.14-2.97), respectively. The HRs (95% CIs)
      for patients who became unemployed, social benefits' recipients, disability or
      age pensioners, widowed patients, and divorced patients were 1.41 (1.01-1.95),
      1.73 (1.06-2.80), 1.45 (0.91-2.30), 2.59 (0.76-8.89), and 1.86 (1.07-3.21),
      respectively. CONCLUSIONS: Suicide risk is generally associated with low income,
      unemployment, educational underachievement, and singleness, but this study
      suggests that the opposite is true among psychiatric patients. However, loss of
      income, labor market status, and marriage increase the suicide risk.

PMID- 18056546
TI  - Increased risk of depressive and anxiety disorders in relatives of patients with
      Parkinson disease.
AB  - CONTEXT: Relatives of patients with Parkinson disease (PD) have an increased risk
      of PD and other neurologic disorders; however, their risk of psychiatric
      disorders remains uncertain. OBJECTIVE: To study the risk of depressive disorders
      and anxiety disorders among first-degree relatives of patients with PD compared
      with first-degree relatives of controls. DESIGN, SETTING, AND PARTICIPANTS: In a
      population-based, historical cohort study, we included 1000 first-degree
      relatives of 162 patients with PD and 850 first-degree relatives of 147 controls.
      Both patients with PD and controls were representative of the population of
      Olmsted County, Minnesota. MAIN OUTCOME MEASURES: Documentation of psychiatric
      disorders was obtained for each relative separately through a combination of
      telephone interviews with the relatives (or their proxies) and review of their
      medical records from a records-linkage system (family study method). Psychiatric
      disorders were defined using clinical criteria from the DSM-IV or routine
      diagnoses. RESULTS: We found an increased risk of several psychiatric disorders
      in first-degree relatives of patients with PD compared with first-degree
      relatives of controls (hazard ratio [HR], 1.54; 95% confidence interval [CI],
      1.21-1.95; P <.001). In particular, we found an increased risk of depressive
      disorders (HR, 1.45; 95% CI, 1.11-1.89; P = .006) and anxiety disorders (HR,
      1.55; 95% CI, 1.05-2.28; P = .03). The results were consistent in analyses that
      adjusted for type of interview, excluded relatives who developed parkinsonism, or
      excluded relatives who developed both a depressive disorder and an anxiety
      disorder. CONCLUSION: These findings suggest that depressive disorders and
      anxiety disorders may share familial susceptibility factors with PD.

PMID- 18056547
TI  - Emotional vitality and incident coronary heart disease: benefits of healthy
      psychological functioning.
AB  - CONTEXT: The potentially toxic effects of psychopathology and poorly regulated
      emotion on physical health have long been considered, but less work has addressed
      whether healthy psychological functioning may also benefit physical health.
      Emotional vitality--characterized by a sense of energy, positive well-being, and
      effective emotion regulation--has been hypothesized to reduce risk of heart
      disease, but no studies have examined this relationship. OBJECTIVES: To examine
      whether emotional vitality is associated with reduced risk of coronary heart
      disease (CHD). Secondary aims are to consider whether effects are independent of
      negative emotion and how they may occur. DESIGN: A prospective population-based
      cohort study. SETTING: National Health and Nutrition Examination Survey I and
      follow-up studies (a probability sample of US adults). PARTICIPANTS: Six thousand
      twenty-five men and women aged 25 to 74 years without CHD at baseline, followed
      up for a mean 15 years after the baseline interview. MAIN OUTCOME MEASURES:
      Measures of incident CHD were obtained from hospital records and death
      certificates. During the follow-up period, 1141 cases of incident CHD occurred.
      RESULTS: At the baseline interview (1971-1975), participants completed the
      General Well-being Schedule from which we derived a measure of emotional
      vitality. Compared with individuals with low levels, those reporting high levels
      of emotional vitality had multivariate-adjusted relative risks of 0.81 (95%
      confidence interval, 0.69-0.94) for CHD. A dose-response relationship was evident
      (P < .001). Significant associations were also found for each individual
      emotional vitality component with CHD, but findings with the overall emotional
      vitality measure were more reliable. Further analyses suggested that one way in
      which emotional vitality may influence coronary health is via health behaviors.
      However, the effect remained significant after controlling for health behaviors
      and other potential confounders, including depressive symptoms or other
      psychological problems. CONCLUSION: Emotional vitality may protect against risk
      of CHD in men and women.

PMID- 18056548
TI  - Intrauterine hormonal environment and risk of developing anorexia nervosa.
AB  - CONTEXT: Anorexia nervosa (AN) is approximately 10 times more common in females
      than in males. The reasons for this difference are not yet understood. Several
      mechanisms have been hypothesized as possible causes. OBJECTIVE: To determine
      whether the different hormonal environments to which male and female fetuses are
      exposed in utero might contribute to the increased risk of developing AN in
      females. DESIGN, SETTING, AND PARTICIPANTS: The study is based on a large
      population-based cohort of Swedish twins. The strategy used is to compare the
      prevalence for AN between same-sex and opposite-sex twins. RESULTS: The study
      shows that the risk of developing AN in female twins is higher than in male
      twins, as expected. The only exception is male members of opposite-sex pairs, who
      have a higher risk of developing the illness when compared with other males (P =
      .62 for narrow diagnostic criteria and P = .60 for broad diagnostic criteria). In
      fact, their risk is at a level that is not statistically significantly different
      from that of females from such a pair. A plausible explanation for this
      phenomenon is that in pregnancies bearing a female fetus, a substance is
      produced, probably hormonal, that increases the risk of having AN in adulthood.
      Because the male half of an opposite-sex twin pair would also be exposed to this
      substance, it could account for the observed elevated risk in males with female
      twins. The most likely candidates are sex steroid hormones. CONCLUSIONS: The
      results of our study are compatible with the hypothesis that intrauterine
      exposure to sex hormones might influence neurodevelopment, affecting the risk of
      developing AN in adult life. This might be a factor contributing to the higher
      risk of developing AN in females.

PMID- 18056549
TI  - Changes in genetic and environmental influences on disordered eating across
      adolescence: a longitudinal twin study.
AB  - CONTEXT: Previous research suggests substantial increases in genetic effects on
      disordered eating across adolescence. Unfortunately, these studies were cross
      sectional and focused primarily on early (age 11 years) vs late (age 17 years)
      adolescence. OBJECTIVE: To examine longitudinal changes in genetic and
      environmental influences on disordered eating across early, mid, and late
      adolescence. DESIGN AND SETTING: Population-based study of female same-sex twins.
      PARTICIPANTS: Seven hundred seventy-two female adolescent twins from the
      Minnesota Twin Family Study assessed at ages 11, 14, and 18 years. MAIN OUTCOME
      MEASURES: Disordered eating symptoms (ie, body dissatisfaction, weight
      preoccupation, binge eating, and the use of compensatory behaviors) were assessed
      with the total score from the Minnesota Eating Behavior Survey. RESULTS:
      Biometric model-fitting indicated significant changes in genetic and shared
      environmental effects across early to mid adolescence. Although genetic factors
      accounted for a negligible proportion (6%) of variance at age 11 years, genes
      increased in importance and accounted for roughly half of the variance (46%) in
      disordered eating at ages 14 and 18 years. Shared environmental influences
      decreased substantially across these same ages. CONCLUSIONS: Findings highlight
      the transition from early to mid adolescence as a critical time for the emergence
      of a genetic diathesis for disordered eating. The increase in genetic effects
      during this developmental stage corroborates previous research implicating
      puberty in the genetic etiology of eating disorders.

PMID- 18056550
TI  - Visual information processing of faces in body dysmorphic disorder.
AB  - CONTEXT: Body dysmorphic disorder (BDD) is a severe psychiatric condition in
      which individuals are preoccupied with perceived appearance defects. Clinical
      observation suggests that patients with BDD focus on details of their appearance
      at the expense of configural elements. This study examines abnormalities in
      visual information processing in BDD that may underlie clinical symptoms.
      OBJECTIVE: To determine whether patients with BDD have abnormal patterns of brain
      activation when visually processing others' faces with high, low, or normal
      spatial frequency information. DESIGN: Case-control study. SETTING: University
      hospital. PARTICIPANTS: Twelve right-handed, medication-free subjects with BDD
      and 13 control subjects matched by age, sex, and educational achievement.
      Intervention Functional magnetic resonance imaging while performing matching
      tasks of face stimuli. Stimuli were neutral-expression photographs of others'
      faces that were unaltered, altered to include only high spatial frequency visual
      information, or altered to include only low spatial frequency visual information.
      MAIN OUTCOME MEASURE: Blood oxygen level-dependent functional magnetic resonance
      imaging signal changes in the BDD and control groups during tasks with each
      stimulus type. RESULTS: Subjects with BDD showed greater left hemisphere activity
      relative to controls, particularly in lateral prefrontal cortex and lateral
      temporal lobe regions for all face tasks (and dorsal anterior cingulate activity
      for the low spatial frequency task). Controls recruited left-sided prefrontal and
      dorsal anterior cingulate activity only for the high spatial frequency task.
      CONCLUSIONS: Subjects with BDD demonstrate fundamental differences from controls
      in visually processing others' faces. The predominance of left-sided activity for
      low spatial frequency and normal faces suggests detail encoding and analysis
      rather than holistic processing, a pattern evident in controls only for high
      spatial frequency faces. These abnormalities may be associated with apparent
      perceptual distortions in patients with BDD. The fact that these findings
      occurred while subjects viewed others' faces suggests differences in visual
      processing beyond distortions of their own appearance.

PMID- 18056551
TI  - Exposure to hurricane-related stressors and mental illness after Hurricane
      Katrina.
AB  - CONTEXT: Uncertainty exists about the prevalence, severity, and correlates of
      mental disorders among people exposed to Hurricane Katrina. OBJECTIVE: To
      estimate the prevalence and associations between DSM-IV anxiety-mood disorders
      and hurricane-related stressors separately among prehurricane residents of the
      New Orleans metropolitan area and the remainder of the areas in Alabama,
      Louisiana, and Mississippi affected by Katrina. DESIGN: Community survey. SETTING
      AND PARTICIPANTS: A probability sample of 1043 English-speaking prehurricane
      residents of the areas affected by Hurricane Katrina was administered via
      telephone survey between January 19 and March 31, 2006. The survey assessed
      hurricane-related stressors and screened for 30-day DSM-IV anxiety-mood
      disorders. MAIN OUTCOME MEASURES: The K6 screening scale of anxiety-mood
      disorders and the Trauma Screening Questionnaire scale for posttraumatic stress
      disorder (PTSD), both calibrated against blinded structured clinical reappraisal
      interviews to approximate the 30-day prevalence of DSM-IV disorders. RESULTS:
      Prehurricane residents of the New Orleans metropolitan area were estimated to
      have a 49.1% 30-day prevalence of any DSM-IV anxiety-mood disorder (30.3%
      estimated prevalence of PTSD) compared with 26.4% (12.5% PTSD) in the remainder
      of the sample. The vast majority of respondents reported exposure to hurricane
      related stressors. Extent of stressor exposure was more strongly related to the
      outcomes in the New Orleans metropolitan area subsample than the remainder of the
      sample. The stressors most strongly related to these outcomes were physical
      illness/injury and physical adversity in the New Orleans metropolitan area
      subsample and property loss in the remainder of the sample. Sociodemographic
      correlates were not explained either by differential exposure or reactivity to
      hurricane-related stressors. CONCLUSIONS: The high prevalence of DSM-IV anxiety
      mood disorders, the strong associations of hurricane-related stressors with these
      outcomes, and the independence of sociodemographics from stressors argue that the
      practical problems associated with ongoing stressors are widespread and must be
      addressed to reduce the prevalence of mental disorders in this population.

PMID- 18056552
TI  - Incidence of drug problems in young adults exposed to trauma and posttraumatic
      stress disorder: do early life experiences and predispositions matter?
AB  - CONTEXT: Most estimated associations of posttraumatic stress disorder (PTSD) with
      DSM-IV drug dependence and abuse are from cross-sectional studies or from
      prospective studies of adults that generally do not take into account suspected
      causal determinants measured in early childhood. OBJECTIVE: To estimate risk for
      incident drug disorders associated with prior DSM-IV PTSD. DESIGN: Multiwave
      longitudinal study of an epidemiologic sample of young adults first assessed at
      entry to first grade of primary school in the fall semesters of 1985 and 1986,
      with 2 young adult follow-up assessments. SETTING: Mid-Atlantic US urban
      community. PARTICIPANTS: Young adults (n = 988; aged 19-24 years) free of
      clinical features of DSM-IV drug use disorders at the first young adult
      assessment and therefore at risk for newly incident drug use disorders during the
      1-year follow-up period. MAIN OUTCOME MEASURES: During the 12-month interval
      between the 2 young adult follow-up assessments, newly incident (1) DSM-IV drug
      abuse or dependence; (2) DSM-IV drug abuse; (3) DSM-IV drug dependence; and (4)
      emerging dependence problems (1 or 2 newly incident clinical features of DSM-IV
      drug dependence), among subjects with no prior clinical features of drug use
      disorders. RESULTS: Prior PTSD (but not trauma only) was associated with excess
      risk for drug abuse or dependence (adjusted relative risk, 4.9; 95% confidence
      interval, 1.6-15.2) and emerging dependence problems (adjusted relative risk,
      4.9; 95% confidence interval, 1.2-20.1) compared with the no-trauma group
      controlling for childhood factors. Subjects with PTSD also had a greater adjusted
      relative risk for drug abuse or dependence compared with subjects exposed to
      trauma only (adjusted relative risk, 2.0; 95% confidence interval, 1.1-3.8)
      controlling for childhood factors. CONCLUSIONS: Association of PTSD with
      subsequent incident drug use disorders remained substantial after statistical
      adjustment for early life experiences and predispositions reported in previous
      studies as carrying elevated risk for both disorders. Posttraumatic stress
      disorder might be a causal determinant of drug use disorders, possibly
      representing complications such as attempts to self-medicate troubling trauma
      associated memories, nightmares, or painful hyperarousal symptoms.

PMID- 18056554
TI  - Is psychosocial management effective?

PMID- 18056553
TI  - Clinical prediction of Alzheimer disease dementia across the spectrum of mild
      cognitive impairment.
AB  - OBJECTIVE: To determine whether clinical assessment methods that grade the
      severity of impairments within the spectrum of mild cognitive impairment (MCI)
      can predict clinical course, particularly among very mildly impaired individuals
      who do not meet formal MCI criteria as implemented in clinical trials. DESIGN:
      Cohort. SETTING: Community volunteers. PARTICIPANTS: From a longitudinal study of
      normal (Clinical Dementia Rating [CDR] = 0; n = 77) and mildly impaired (CDR =
      0.5; n = 167) participants with 5 or more annual clinical assessments, baseline
      level of cognitive impairment in daily life was graded using CDR sum of boxes
      (CDR-SB) and level of cognitive performance impairment was graded using
      neuropsychological test scores. MAIN OUTCOME MEASURES: Five-year outcome measures
      included (1) probable Alzheimer disease (AD) diagnosis and (2) clinical "decline"
      (CDR-SB increase > or = 1.0). Logistic regression models were used to assess the
      ability of baseline measures to predict outcomes in the full sample and
      separately in the subjects who did not meet formal MCI criteria as implemented in
      a multicenter clinical trial (n = 125; "very mild cognitive impairment" [vMCI]).
      RESULTS: The presence of both higher CDR-SB and lower verbal memory and executive
      function at baseline predicted greater likelihood of probable AD and decline.
      Five-year rates of probable AD and decline in vMCI (20%, AD; 49%, decline) were
      intermediate between normal participants (0%, AD; 28%, decline) and participants
      with MCI (41%, AD; 62%, decline). Within vMCI, likelihood of probable AD was
      predicted by higher CDR-SB and lower executive function. CONCLUSIONS: Even in
      very mildly impaired individuals who do not meet strict MCI criteria as
      implemented in clinical trials, the degree of cognitive impairment in daily life
      and performance on neuropsychological testing predict likelihood of an AD
      diagnosis within 5 years. The clinical determination of relative severity of
      impairment along the spectrum of MCI may be valuable for trials of putative
      disease-modifying compounds, particularly as target populations are broadened to
      include less impaired individuals.

PMID- 18056555
TI  - Trauma in childhood.

PMID- 18056556
TI  - Efficacy of a parent-based sexual-risk prevention program for African American
      preadolescents: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of a parent-based sexual-risk prevention
      program for African American preadolescents. DESIGN: Randomized controlled trial.
      SETTING: Community-based study conducted in Athens, Georgia; Atlanta, Georgia;
      and Little Rock, Arkansas from 2001 to 2004. PARTICIPANTS: From 1545 inquiries,
      1115 African American parent-preadolescent dyads (child, aged 9-12 years) formed
      the analytic sample. INTERVENTION: Participants were randomized into 1 of 3 study
      arms: enhanced communication intervention (five 2 1/2-hour sessions), single
      session communication intervention (one 2 1/2-hour session), and general health
      intervention (control, one 2 1/2-hour session). OUTCOME MEASURES: Continuous
      measures of parent-preadolescent sexual communication and parental responsiveness
      to sex-related questions at preintervention, postintervention, and at 6- and 12
      month follow-ups; and dichotomous measure of preadolescent sexual risk (having
      engaged in or intending to engage in sexual intercourse at 12-month follow-up).
      RESULTS: Using intent-to-treat participants, differences of mean change from
      baseline for continuous measures and relative risk for the dichotomous measure of
      sexual risk were calculated. Participants in the enhanced intervention had higher
      mean changes from baseline scores, indicating more sexual communication and
      responsiveness to sexual communication at each assessment after intervention for
      all continuous measures than those in the control intervention and single-session
      intervention. Preadolescents whose parents attended all 5 sessions of the
      enhanced intervention had a likelihood of sexual risk at the 12-month follow-up
      of less than 1.00 relative to those whose parents attended the control (relative
      risk, 0.65; 95% confidence interval, 0.41-1.03) and single-session (relative
      risk, 0.62; 95% confidence interval, 0.40-0.97) interventions. CONCLUSIONS: These
      results provide preliminary evidence for the efficacy of a parenting program
      designed to teach sexual communication skills to prevent sexual risk in
      preadolescents. TRIAL REGISTRATION; clinicaltrials.gov Identifier: NCT00137943.

PMID- 18056557
TI  - Reduction in human immunodeficiency virus risk among youth in developing
      countries.
AB  - OBJECTIVE: To address the 6-month efficacy of a human immunodeficiency virus
      (HIV) prevention intervention targeted to youth and delivered with and without a
      parental monitoring intervention in a developing country (the Bahamas). DESIGN:
      Randomized, controlled, 3-cell intervention trial with a 6-month postintervention
      follow-up. SETTING: Elementary schools in the Bahamas. PARTICIPANTS: A total of
      1282 Bahamian sixth-grade students (and 1175 parents) in 15 schools.
      INTERVENTIONS: Youth and parents were randomized at the level of the school to
      receive the following interventions: (1) Focus on Youth in the Caribbean (FOYC)
      plus Caribbean Informed Parents and Children Together (CImPACT), (2) FOYC plus an
      attention control for parents (Goal for It [GFI]), or (3) an attention control
      for the youth (Wonderous Wetlands [WW]) plus the GFI. The 10-session FOYC or WW
      curriculum was delivered as part of the elementary school curriculum. The GFI or
      CImPACT was delivered to parents in the evenings or on weekends. MAIN OUTCOME
      MEASURES: Risk and protective knowledge, condom use skills, perceptions,
      interventions, and self-reported behaviors. RESULTS: Compared with the WW, the
      FOYC significantly increased knowledge, condom use skills, protective
      perceptions, and intentions to engage in safer behaviors. Among youth, no
      differences were found in knowledge or condom use skills based on parent
      intervention; among parents, those receiving the CImPACT demonstrated superior
      condom use skills after the intervention. CONCLUSIONS: Protective knowledge,
      skills, perceptions, and intentions of youth from 1 developing country can be
      significantly improved by youth intervention delivered through the schools.
      Longer follow-up is needed to determine if risk behaviors will be reduced and how
      long protective results will be sustained.

PMID- 18056558
TI  - Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep
      quality for coughing children and their parents.
AB  - OBJECTIVES: To compare the effects of a single nocturnal dose of buckwheat honey
      or honey-flavored dextromethorphan (DM) with no treatment on nocturnal cough and
      sleep difficulty associated with childhood upper respiratory tract infections.
      DESIGN: A survey was administered to parents on 2 consecutive days, first on the
      day of presentation when no medication had been given the prior evening and then
      the next day when honey, honey-flavored DM, or no treatment had been given prior
      to bedtime according to a partially double-blinded randomization scheme. SETTING:
      A single, outpatient, general pediatric practice. PARTICIPANTS: One hundred five
      children aged 2 to 18 years with upper respiratory tract infections, nocturnal
      symptoms, and illness duration of 7 days or less. INTERVENTION: A single dose of
      buckwheat honey, honey-flavored DM, or no treatment administered 30 minutes prior
      to bedtime. MAIN OUTCOME MEASURES: Cough frequency, cough severity, bothersome
      nature of cough, and child and parent sleep quality. RESULTS: Significant
      differences in symptom improvement were detected between treatment groups, with
      honey consistently scoring the best and no treatment scoring the worst. In paired
      comparisons, honey was significantly superior to no treatment for cough frequency
      and the combined score, but DM was not better than no treatment for any outcome.
      Comparison of honey with DM revealed no significant differences. CONCLUSIONS: In
      a comparison of honey, DM, and no treatment, parents rated honey most favorably
      for symptomatic relief of their child's nocturnal cough and sleep difficulty due
      to upper respiratory tract infection. Honey may be a preferable treatment for the
      cough and sleep difficulty associated with childhood upper respiratory tract
      infection. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00127686.

PMID- 18056559
TI  - The effect of honey on nocturnal cough and sleep quality for children and their
      parents.

PMID- 18056560
TI  - Accuracy of adolescent self-report of height and weight in assessing overweight
      status: a literature review.
AB  - OBJECTIVE: To examine the accuracy of self-reported height and weight data to
      classify adolescent overweight status. Self-reported height and weight are
      commonly used with minimal consideration of accuracy. DATA SOURCES: Eleven
      studies (4 nationally representative, 7 convenience sample or locally based).
      STUDY SELECTION: Peer-reviewed articles of studies conducted in the United States
      that compared self-reported and directly measured height, weight, and/or body
      mass index data to classify overweight among adolescents. MAIN EXPOSURES: Self
      reported and directly measured height and weight. MAIN OUTCOME MEASURES:
      Overweight prevalence; missing data, bias, and accuracy. RESULTS: Studies varied
      in examination of bias. Sensitivity of self-reported data for classification of
      overweight ranged from 55% to 76% (4 of 4 studies). Overweight prevalence was 
      0.4% to -17.7% lower when body mass index was based on self-reported data vs
      directly measured data (5 of 5 studies). Females underestimated weight more than
      males (ranges, -4.0 to -1.0 kg vs -2.6 to 1.5 kg, respectively) (9 of 9 studies);
      overweight individuals underestimated weight more than nonoverweight individuals
      (6 of 6 studies). Missing self-reported data ranged from 0% to 23% (9 of 9
      studies). There was inadequate information on bias by age and race/ethnicity.
      CONCLUSIONS: Self-reported data are valuable if the only source of data. However,
      self-reported data underestimate overweight prevalence and there is bias by sex
      and weight status. Lower sensitivities of self-reported data indicate that one
      fourth to one-half of those overweight would be missed. Other potential biases in
      self-reported data, such as across subgroups, need further clarification. The
      feasibility of collecting directly measured height and weight data on a
      state/community level should be explored because directly measured data are more
      accurate.

PMID- 18056561
TI  - Health care utilization for pneumonia in young children after routine
      pneumococcal conjugate vaccine use in the United States.
AB  - OBJECTIVE: To estimate the effect of 7-valent pneumococcal conjugate vaccine
      (PCV7) on rates of pneumonia-related health care utilization and costs in
      children younger than 2 years. DESIGN: Retrospective population study. SETTING:
      Approximately 40 large employers each year, from 1997 to 2004. PARTICIPANTS:
      Enrollees in the MarketScan databases collected by Thomson Medstat. MAIN
      EXPOSURE: Pneumococcal conjugate vaccine immunization program. MAIN OUTCOME
      MEASURES: Rates of International Classification of Diseases, Ninth Revision-coded
      hospitalizations and ambulatory visits due to all-cause and pneumococcal
      pneumonia and their medical expenditures. RESULTS: Comparing the rates in 2004
      with those in the baseline period of 1997 to 1999 among children younger than 2
      years, hospitalizations due to all-cause pneumonia declined from 11.5 to 5.5 per
      1000 children (52.4% decline; P < .001) and ambulatory visits due to all-cause
      pneumonia declined from 99.3 to 58.5 per 1000 children (41.1% decline; P < .001).
      Rates of hospitalizations due to pneumococcal pneumonia declined from 0.6 to 0.3
      per 1000 children (57.6% decline; P < .001) and rates of ambulatory visits
      declined from 1.7 to 0.9 per 1000 children (46.9% decline; P < .001). Projecting
      from these data to the US population, the total estimated direct medical
      expenditures for all-cause pneumonia-related hospitalizations and ambulatory
      visits in young children were reduced from an annual average of $688.2 million
      during the period of 1997 to 1999 to $376.7 million in 2004 (45.3% decline and
      approximately $310 million decrease). CONCLUSIONS: In children younger than 2
      years, the age group targeted for vaccination, pneumonia-related health care
      utilization in a privately insured population declined substantially following
      PCV7 introduction. These results suggest that PCV7 may play an important role in
      reducing the burden of pneumonia, resulting in major savings in medical care
      cost.

PMID- 18056562
TI  - Discussion of illness during well-child care visits with parents of children with
      and without special health care needs.
AB  - OBJECTIVES: To compare parents of children with special health care needs (CSHCN)
      with other parents to determine parents' expectations and priorities for
      discussing concerns related to a child's acute or chronic illness at well-child
      care visits, the association of unmet expectations and priorities with
      satisfaction, and whether discussing illness displaces prevention topics. DESIGN:
      Written, self-administered survey of parents at well-child care visits. SETTING:
      Two community-based pediatric practices in suburban southeast Michigan.
      PARTICIPANTS: Five hundred parents with children aged 6 months to 12 years. MAIN
      EXPOSURE: Having a special health care need. MAIN OUTCOME MEASURES: Expectations
      and priorities for discussing illness-related topics (chronic and acute
      illnesses, medications, specialist referrals, and effects of health on life
      overall), actual discussion regarding illness and preventive topics, and
      satisfaction. RESULTS: Compared with parents of children without chronic
      conditions, parents of CSHCN were more likely to expect to discuss their child's
      illness (81% vs 92%, respectively; P < .001); 79% of parents of CSHCN ranked
      illness among their top 3 priorities (vs 53% of other parents [P < .001]).
      Parents of CSHCN reported discussing a mean of 3.2 illness topics, as compared
      with a mean of 2.2 illness topics for other parents (P < .001). Having more than
      1 unmet expectation for discussing illness was associated with higher odds of
      lower satisfaction (for parents of CSHCN: odds ratio, 7.2; 95% confidence
      interval, 2.9-18.3; for other parents: odds ratio, 3.0; 95% confidence interval,
      1.7-5.5). Discussing more illness topics was associated with discussing more
      preventive topics (P < .001). CONCLUSIONS: Discussing illness is frequently
      expected and highly prioritized at well-child care visits, particularly for
      parents of CSHCN. Unmet expectations are associated with lower satisfaction.
      Incorporating illness concerns at well-child care visits may improve chronic
      disease management.

PMID- 18056563
TI  - Hepatitis B vaccination and the risk of childhood-onset multiple sclerosis.
AB  - OBJECTIVE: To investigate whether vaccination against hepatitis B (HB) increases
      the risk of incident multiple sclerosis (MS) in childhood in the short and long
      terms. DESIGN: Case-control study. SETTING: Population-based study conducted in
      France from January 1, 1994, to December 31, 2003. PARTICIPANTS: The case
      patients had incident MS with onset before age 16 years. Each case was
      individually matched for age, sex, and geographic location (current place of
      residence) to 12 control participants randomly selected from the general
      population of France. EXPOSURE: Hepatitis B vaccine. MAIN OUTCOME MEASURE: The
      risk of MS associated with HB vaccine exposure. RESULTS: One hundred forty-three
      case patients with MS were matched to 1122 control participants. The rate of HB
      vaccination in the 3 years before the index date was approximately 32% for both
      cases and controls. Vaccination against HB within the 3-year study period was not
      associated with an increased rate of a first episode of MS (adjusted odds ratio,
      1.03; 95% confidence interval, 0.62-1.69). The rate was also not increased for HB
      vaccination within 6 months of the index date or at any time since birth or as a
      function of the number of injections or the brand of HB vaccine. CONCLUSION:
      Vaccination against HB does not seem to increase the risk of a first episode of
      MS in childhood.

PMID- 18056564
TI  - Growth of the corpus callosum in adolescents born preterm.
AB  - OBJECTIVE: To examine the growth of the corpus callosum between adolescence and
      early adulthood in individuals who were born before 33 weeks' gestation (very
      preterm [VPT]) and its relation to neuropsychological function. DESIGN: A
      longitudinal cohort study of VPT individuals born between January 4, 1982, and
      December 29, 1984, and a term-born comparison group. SETTING: A long-term follow
      up study into perinatal predictors of outcome after preterm birth at University
      College Hospital, London. PARTICIPANTS: A total of 72 VPT and 34 term-born
      individuals were assessed in adolescence (aged 15 years) and in early adulthood
      (aged 19 years). Adult assessments took place between June 6, 2002, and October
      23, 2004. MAIN EXPOSURE: Birth before 33 weeks' gestation. OUTCOME MEASURE: The
      cross-sectional area of 4 segments of the corpus callosum, measured on the
      midsagittal slice of high-resolution structural magnetic resonance images in
      adolescence and young adulthood. RESULTS: Total corpus callosum size increased in
      term and VPT groups, but growth was much greater in the VPT group (13.4% in the
      VPT group vs 3.3% in the term group). There were significant associations between
      adult performance IQ and growth of anterior (P = .001), midposterior (P = .009),
      and posterior (P = .009) segments in the VPT group. CONCLUSIONS: The corpus
      callosum grows dramatically in VPT adolescents, and this growth is associated
      with neuropsychological outcome. This may represent a delay of a normal
      maturational process in VPT individuals.

PMID- 18056565
TI  - What new information pediatric autopsies can provide: a retrospective evaluation
      of 100 consecutive autopsies using family-centered criteria.
AB  - OBJECTIVE: To determine the proportions of pediatric autopsies yielding various
      types of new information (eg, genetic diagnosis, additional explanation) that
      might be valued by families. DESIGN: Retrospective case series analysis. SETTING:
      Large urban children's hospital. PARTICIPANTS: One hundred consecutive autopsies,
      2003-2004. INTERVENTION: Using both traditional criteria and a novel
      classification scheme developed with expert clinicians and nonmedical parent
      faculty, 3 reviewers independently assessed each case for new information found
      at autopsy. Classifications were based on unanimous consensus. MAIN OUTCOME
      MEASURE: Proportions of autopsies yielding new information. RESULTS: Decedents'
      ages ranged from 1 to 24 years. Using traditional criteria, major unexpected
      findings related to death occurred in 28% of the autopsies. Applying our novel
      criteria to the same 100 autopsies, we found new information that had the
      potential to further clarify the cause(s) of a child's death (53% of cases);
      inform the future reproductive choices of either the parents (10%) or siblings
      (8%); affect siblings' future health care (6%); or contribute to patient care
      quality control (36%) or publishable knowledge (7%). CONCLUSIONS: Pediatric
      autopsies can yield different types of information that may be important to
      families. While the proportion of autopsies providing specific types of new
      information will vary between hospitals (depending on case mix, autopsy policies,
      and clinician/pathologist expertise) and across time (depending on available
      diagnostic modalities), hospital-specific data classified in this manner may be
      useful to physicians counseling families about autopsy.

PMID- 18056566
TI  - Persistence and remission in childhood asthma: a population-based asthma birth
      cohort study.
AB  - OBJECTIVES: To examine and predict the persistence of childhood asthma. DESIGN:
      Longitudinal population-based cohort study. SETTING: Ontario, Canada.
      PARTICIPANTS: Children born in 1994 and diagnosed with asthma before age 6 years
      were followed up until age 11 years. Diagnosis of asthma was defined as 1 asthma
      hospitalization or 2 asthma physician claims within 3 years prior to age 6 years.
      MAIN EXPOSURE: Intensity of health services use within 1 year postdiagnosis. MAIN
      OUTCOME MEASURES: Those who continued to have asthma events (hospitalization
      and/or physician visit) between ages 6 and 11 years were considered to have
      "persistent asthma," while others were in "remission." Cumulative rates of health
      services use for asthma during follow-up were calculated. Logistic regression
      analysis was used to estimate risks of persistent asthma. RESULTS: The study
      included 34,216 children diagnosed with asthma before age 6 years. More than half
      (54.4%) experienced a second asthma health care encounter within 1 year after
      diagnosis. By age 12 years, nearly half (48.6%) were in remission. Children with
      asthma hospitalization during the first year postdiagnosis had a 3-fold risk of
      persistent asthma by age 12 years (95% confidence interval, 2.69-3.39; P < .001).
      Those with at least 4 physician visits also had a 2.6-fold risk of persistent
      asthma during follow-up (95% confidence interval, 2.34-2.81; P < .001).
      CONCLUSION: The concentration of health services use within 1 year following the
      initial diagnosis of childhood asthma points to the need for attentive follow-up
      and ongoing management and education strategies in the early years.

PMID- 18056567
TI  - Maternal waist circumference and the prediction of children's metabolic syndrome.
AB  - OBJECTIVE: To determine the association between metabolic syndrome (MS)
      components in 620 children and their mothers. DESIGN: Cross-sectional assessment.
      SETTING: Three public elementary schools in Buenos Aires, Argentina.
      PARTICIPANTS: A total of 620 students at a mean +/- SD age of 9.00 +/- 2.07 years
      and their mothers at a mean +/- SD age of 37.69 +/- 7.19 years. MAIN OUTCOMES
      MEASURES: The association between MS in children and components of MS in their
      mothers, such as body mass index (BMI) (calculated as weight in kilograms divided
      by height in meters squared), high-density lipoprotein cholesterol concentration,
      triglycerides concentration, glucose concentration, homeostasis model assessment
      of insulin resistance, blood pressure, and age. RESULTS: Ninety-five (15.3%) of
      the children were obese (BMI > or = 95th percentile), 108 (17.4%) were overweight
      (BMI > or = 85th percentile and < 95th percentile), and 418 (67.3%) were a
      healthy weight (BMI < 85th percentile). One hundred twelve (18.1%) of the mothers
      were obese (BMI > or = 30), 183 (29.5%) were overweight (BMI > or = 25 and < 30),
      and 325 (52.4%) were a healthy weight (BMI < 25). Low concentration of high
      density lipoprotein cholesterol (in 46.0% and 56.9% of mothers and children,
      respectively) and central obesity (in 36.0% and 25.0% of mothers and children,
      respectively) were common, whereas hypertension (in 10.5% and 1.9% of mothers and
      children, respectively) and impaired fasting glucose (in 2.9% and 0.3% of mothers
      and children, respectively) were infrequent. The prevalence of MS was 10.8% in
      children and 11.0% in mothers. Central obesity was less frequent in mothers of
      children without MS vs mothers of those with MS (41.2% vs 78.8%, respectively; P
      < .001). Mothers of children without MS had fewer MS components than did mothers
      of children with MS (BMI z score, 0.09 vs 0.69, respectively [P < .001]; waist
      circumference z score, 0.15 vs 0.87, respectively [P < .001]). Mothers' waist
      circumference was a significant independent predictor of their children's MS when
      adjusted for mothers' concentrations of triglycerides, cholesterol, and glucose
      and age (odds ratio, 2.11; 95% confidence interval, 1.36-3.26). CONCLUSION: A
      mother's waist circumference predicts her child's MS, consistent with known
      familial associations of obesity and type 2 diabetes.

PMID- 18056568
TI  - Picture of the month--quiz case. Scrofuloderma with lupus vulgaris.

PMID- 18056569
TI  - The march of science.

PMID- 18056570
TI  - Should children with special health care needs have separate preventive care
      visits?

PMID- 18056571
TI  - Sequential survey of body piercing and tattooing prevalence and medical
      complication incidence among college students.

PMID- 18056573
TI  - Clinical reasoning: a case of multiple intracerebral hemorrhages.

PMID- 18056574
TI  - Highlights of the December 4 issue.

PMID- 18056575
TI  - Enumerating Meissner corpuscles: future gold standard of large fiber sensorimotor
      polyneuropathy?

PMID- 18056576
TI  - What you see is what you get: coupling function with structure in the visual
      system.

PMID- 18056577
TI  - Altered functional and structural connectivities in patients with MS: a 3-T
      study.
AB  - OBJECTIVE: To determine the functional and structural substrates of motor network
      dysfunction in patients with relapsing-remitting multiple sclerosis (RRMS).
      METHODS: Using a 3-T scanner, in 12 right-handed RRMS patients and 14 matched
      controls, we acquired diffusion tensor (DT) MRI and functional MRI during the
      performance of a simple motor task with the right (R) hand. Using DT MRI
      tractography, we calculated DT-derived metrics from several motor and nonmotor
      white matter (WM) fiber bundles. Functional connectivity analysis was performed
      using SPM2. RESULTS: Compared with control, MS patients had abnormal DT MRI
      metrics of all the WM bundles studied. Compared with controls, MS patients had
      more significant activations of the left (L) supplementary motor area (SMA), the
      L primary sensorimotor cortex (SMC), and the R cerebellum. They also had
      increased functional connectivity between the R primary SMC and the R cerebellum
      (p = 0.01) and the L SMA and the L primary SMC (p = 0.04). Coefficients of
      altered connectivity were correlated with structural MRI metrics of tissue damage
      of the corticospinal and the dentatorubrothalamic tract (r values ranging from 
      0.73 to 0.85). CONCLUSIONS: The correlations found between measures of functional
      connectivity and structural damage to some of the major brain motor white matter
      bundles suggest an adaptive role of functional connectivity changes in limiting
      the clinical consequences of structural damage in patients with relapsing
      remitting multiple sclerosis. Combining measures of altered functional and
      structural connectivities of specific brain networks is a promising tool to
      elucidate the mechanisms responsible for clinical manifestations of CNS damage.

PMID- 18056578
TI  - A structural basis for reading fluency: white matter defects in a genetic brain
      malformation.
AB  - BACKGROUND: Multiple lines of evidence have suggested that developmental dyslexia
      may be associated with abnormalities of neuronal migration or axonal
      connectivity. In patients with periventricular nodular heterotopia--a rare
      genetic brain malformation characterized by misplaced nodules of gray matter
      along the lateral ventricles--a specific and unexpected reading disability is
      present, despite normal intelligence. We sought to investigate the cognitive and
      structural brain bases of this phenomenon. METHODS: Ten adult subjects with
      heterotopia, 10 with dyslexia, and 10 normal controls were evaluated, using a
      battery of neuropsychometric measures. White matter integrity and fiber tract
      organization were examined in six heterotopia subjects, using diffusion tensor
      imaging methods. RESULTS: Subjects with heterotopia and those with developmental
      dyslexia shared a common behavioral profile, with specific deficits in reading
      fluency. Individuals with dyslexia seemed to have a more prominent phonological
      impairment than heterotopia subjects. Periventricular nodular heterotopia was
      associated with specific, focal disruptions in white matter microstructure and
      organization in the vicinity of gray matter nodules. The degree of white matter
      integrity correlated with reading fluency in this population. CONCLUSIONS: We
      demonstrate that a genetic disorder of gray matter heterotopia shares behavioral
      characteristics with developmental dyslexia, and that focal white matter defects
      in this disorder may serve as the structural brain basis of this phenomenon. Our
      findings represent a potential model for the use of developmental brain
      malformations in the investigation of abnormal cognitive function.

PMID- 18056579
TI  - The AMC Linear Disability Score in patients with newly diagnosed Parkinson
      disease.
AB  - OBJECTIVE: The aim of this study was to examine the clinimetric properties of the
      AMC Linear Disability Score (ALDS), a new generic disability measure based on
      Item Response Theory, in patients with newly diagnosed Parkinson disease (PD).
      METHODS: A sample of 132 patients with PD was evaluated using the Hoehn and Yahr
      (H&Y), the Unified PD Rating Scale motor examination, the Schwab and England
      scale (S&E), the Short Form-36, the PD Quality of Life Questionnaire, and the
      ALDS. RESULTS: The internal consistency reliability of the ALDS was good (alpha =
      0.95) with 55 items extending the sufficient item-total correlation criterion (r
      > 0.20). The ALDS was correlated with other disability measures (r = 0.50 to
      0.63) and decreasingly associated with measures reflecting impairments (r = 0.36
      to 0.37) and mental health (r = 0.23 to -0.01). With regard to know-group
      validity, the ALDS indicated that patients with more severe PD (H&Y stage 3) were
      more disabled than patients with mild (H&Y stage 1) or moderate PD (H&Y stage 2)
      (p < 0.0001). The ALDS discriminated between more or less severe extrapyramidal
      symptoms (p = 0.001) and patients with postural instability showed lower ALDS
      scores compared to patients without postural instability (p = or< 0.0001).
      Compared to the S&E (score 100% = 19%), the ALDS showed less of a ceiling effect
      (5%). CONCLUSION: The AMC Linear Disability Score is a flexible, feasible, and
      clinimetrically promising instrument to assess the level of disability in
      patients with newly diagnosed Parkinson disease.

PMID- 18056580
TI  - Neurophysiologic study of central pain in patients with Parkinson disease.
AB  - BACKGROUND: Patients with Parkinson disease (PD) may present with various types
      of pain. In some instances, no cause can be identified and pain is considered a
      primary disorder (primary central pain [PCP]). We hypothesized that PCP in
      patients with PD (PD-PCP) may be due to a dysfunction of pain pathways or the
      processing of pain inputs in the CNS. METHODS: We carried out a psychophysical
      and neurophysiologic study in 9 patients with PD-PCP, 9 patients with PD without
      pain (PD-NoP), and 9 healthy control subjects. We assessed the clinical
      characteristics of pain, performed quantitative sensory testing with thermal
      probes, and recorded laser-evoked potentials (LEPs) and laser-induced sudomotor
      skin responses (1-SSRs) in "off" and "on" conditions. RESULTS: In "off"
      condition, patients with PD-PCP had lower heat pain and laser pinprick
      thresholds, higher LEP amplitudes, and less habituation of the l-SSR in
      comparison with PD-NoP patients and control subjects. Abnormalities were more
      marked in the most affected side. In "on" condition, psychophysical and
      neurophysiologic differences disappeared or were significantly attenuated.
      CONCLUSION: Conduction along peripheral and central pain pathways is normal in
      patients with Parkinson disease with or without primary central pain. However,
      apart from signs of hyperalgesia, our patients exhibited lack of habituation of
      sympathetic sudomotor responses to repetitive pain stimuli, suggesting an
      abnormal control of the effects of pain inputs on autonomic centers.
      Abnormalities were attenuated by l-dopa, suggesting that the dysfunction may
      occur in dopamine-dependent centers regulating both autonomic function and
      inhibitory modulation of pain inputs.

PMID- 18056581
TI  - Systematic analysis of three FHM genes in 39 sporadic patients with hemiplegic
      migraine.
AB  - BACKGROUND: Familial (FHM) and sporadic (SHM) hemiplegic migraine are severe
      subtypes of migraine associated with transient hemiparesis. For FHM, three genes
      have been identified encoding subunits of a calcium channel (CACNA1A), a sodium
      potassium pump (ATP1A2), and a sodium channel (SCN1A). Their role in SHM is
      unknown. Establishing a genetic basis for SHM may further the understanding of
      its pathophysiology and relationship with common types of migraine. It will also
      facilitate the often difficult differential diagnosis from other causes of
      transient hemiparesis. METHODS: We systematically scanned 39 well-characterized
      patients with SHM without associated neurologic features for mutations in the
      three FHM genes. Functional assays were performed for all new sequence variants.
      RESULTS: Sequence variants were identified in seven SHM patients: one CACNA1A
      mutation, five ATP1A2 mutations, and one SCN1A polymorphism. All six mutations
      caused functional changes in cellular assays. One SHM patient later changed to
      FHM because another family member developed FHM attacks. CONCLUSION: We show that
      FHM genes are involved in at least a proportion of SHM patients without
      associated neurologic symptoms. Screening of ATP1A2 offers the highest likelihood
      of success. Because FHM gene mutations were also found in family members with
      "nonhemiplegic" typical migraine with and without aura, our findings reinforce
      the hypothesis that FHM, SHM, and "normal" migraine are part of a disease
      spectrum with shared pathogenetic mechanisms.

PMID- 18056582
TI  - Neonatal status epilepticus vs recurrent neonatal seizures: clinical findings and
      outcome.
AB  - BACKGROUND: Although most children with status epilepticus have a good prognosis,
      its effects on newborns are unclear. OBJECTIVE: We compare the neurodevelopmental
      consequences of recurrent seizures and status epilepticus in newborns. METHODS:
      One hundred six newborns with video-EEG-confirmed seizures, consecutively
      admitted to the neonatal intensive care unit of the University of Parma between
      January 1999 and December 2004, were enrolled in the study. Fifty-one were
      preterm and 55 were full-term newborns. Neonatal status epilepticus was defined
      as continuous seizure activity for at least 30 minutes or recurrent seizures
      lasting a total of >30 minutes without definite return to the baseline neurologic
      condition of the newborn between seizures. Neurologic outcome was assessed at 24
      months of corrected age. RESULTS: Thirty-six newborns had a normal outcome, 20
      died, and 50 presented an adverse outcome. All but 1 of the 26 subjects with
      neonatal status epilepticus had an adverse outcome. Birth weight, severely
      abnormal cerebral ultrasound scans, and status epilepticus were independent
      predictors of abnormal outcome. Depending on gestational age (GA), neonatal
      status epilepticus seems to be a risk factor of adverse outcome in full-term
      newborns (GA >or= 37 weeks: odds ratio [OR] 20.312, 95% CI 2.417 to 170.679, p =
      0.006), and a risk factor of epilepsy in early preterm and full-term newborns (GA
      <or= 29 weeks: OR 10.500, 95% CI 1.211 to 91.026, p = 0.033; GA >or= 37 weeks: OR
      6.517, 95% CI 1.321 to 32.148, p = 0.021). CONCLUSION: Newborns with status
      epilepticus are at high risk of severe neurologic disability and postneonatal
      epilepsy. This is particularly evident in early preterm and full-term infants.

PMID- 18056583
TI  - CIND and MCI in the Italian elderly: frequency, vascular risk factors,
      progression to dementia.

PMID- 18056584
TI  - Toxicokinetics and tissue distribution of deltamethrin in adult Sprague-Dawley
      rats.
AB  - The objectives of this study were twofold: (1) to characterize the toxicokinetics
      and dose-dependent systemic/tissue distribution of deltamethrin (DLM) over a
      range of doses in adult Sprague-Dawley (S-D) rats; (2) to provide comprehensive
      time course blood and tissue data for development of a physiologically based
      toxicokinetic (PBTK) model for DLM. DLM is one of the more neurotoxic members of
      a relatively new and commonly used class of insecticides, the pyrethroids.
      Despite widespread exposure of the general population to pyrethroids, there is
      little basic toxicokinetic (TK) data to use in health risk assessments or in
      development of PBTK models. Male S-D rats were dosed orally with 0.4, 2, or 10 mg
      DLM/kg dissolved in glycerol formal (GF). Another group received 2 mg/kg iv.
      Serial blood and tissue samples were taken at sacrifice and analyzed by high
      performance liquid chromatography for their DLM content, in order to obtain
      comprehensive time course data sets for estimation of classical TK, as well as
      PBTK parameters (e.g., tissues:blood partition coefficients). Gastrointestinal
      (GI) absorption of DLM was rapid but incomplete. Bioavailability was just 18%.
      Some 83% of DLM in blood was present in the plasma. Just 0.1-0.3% of systemically
      absorbed doses reached the brain, the target organ of the bioactive parent
      compound. Fat, skin and surprisingly, skeletal muscle, accumulated large amounts
      of the highly lipophilic chemical and served as slow-release depots. Tissue
      distribution was dose dependent, though generally not proportional to dose.
      Clearance was dose independent in this dosage range. The time-profiles were used
      by A. Mirfazaelian et al. (2006, Toxicol. Sci. 93, 432-442) to construct and
      adjust a PBTK model. Much remains to be learned about physiological/biochemical
      processes and barriers that govern the GI absorption, transport, brain
      deposition, and elimination of DLM and other pyrethroids in laboratory animals
      and humans.

PMID- 18056586
TI  - Beyond the "science of sophomores": does the rational choice explanation of crime
      generalize from university students to an actual offender sample?
AB  - Much of the criminological literature testing rational choice theory has utilized
      hypothetical scenarios presented to university students. Although this research
      generally supports rational choice theory, a common criticism is that conclusions
      from these studies may not generalize to samples of actual offenders. This study
      proceeds to examine this issue in two steps. First, a traditional sample of
      university students is examined to determine how various costs and benefits
      relate to their hypothetical likelihood of offending. Then the same data
      collection procedures are employed with a somewhat different sample of younger,
      adjudicated, and institutionalized offenders to determine whether the conclusions
      drawn from the student sample generalize to this offender sample. Results
      generally suggest that the content and process of hypothetical criminal decision
      making differ in the sample of known offenders relative to the university
      students. Limitations of the current study, as well as suggestions for future
      research, are discussed.

PMID- 18056587
TI  - What shall I do now? Released offenders' expectations for supervision upon
      release.
AB  - In an outcome evaluation of recovering addicts who participated in a prison-based
      therapeutic community, 39 clients (a nonrandomized subsample) were interviewed
      about their rehabilitation and reintegration experience. The study focused on
      participants' perceptions of how essential the continuum of treatment and
      supervision after release was. Whereas many studies have shown that participating
      in prison-based drug treatment programs reduces likelihood of recidivism, clients
      in this study suggested that other factors might be equally important-in
      particular, the importance of the continuum of treatment after release and/or
      being supervised in the community. Findings are discussed in regard to inmates'
      expectations, confusion upon release, and formal support mechanisms; suggestions
      for further research are made.

PMID- 18056588
TI  - Food for all.

PMID- 18056589
TI  - Ideological chasms divide US presidential hopefuls.

PMID- 18056590
TI  - India moves to improve black fever tracking.

PMID- 18056591
TI  - Prescribing patterns drive up health care costs.

PMID- 18056592
TI  - Searching for solutions to the North's quiet epidemic.

PMID- 18056593
TI  - Gairdner winners honoured at Toronto symposium.

PMID- 18056594
TI  - West Nile rates soar in 2007.

PMID- 18056595
TI  - Goats and sewing machines.

PMID- 18056596
TI  - Pediatric hypocalcemia: making the diagnosis.

PMID- 18056597
TI  - Necrobiosis lipoidica diabeticorum.

PMID- 18056598
TI  - Appropriateness of current thresholds for obesity-related measures among
      Aboriginal people.
AB  - BACKGROUND: Despite the high prevalence of obesity and diabetes in the Canadian
      Aboriginal population, it is unknown whether the current thresholds for body mass
      index and waist circumference derived from white populations are appropriate for
      Aboriginal people. We compared the risk of cardiovascular disease among Canadian
      Aboriginal and European populations using the current thresholds for body mass
      index and waist circumference. METHODS: Healthy Aboriginal (n = 195) and European
      (n = 201) participants (matched for sex and body mass index range) were assessed
      for demographic characteristics, lifestyle factors, total and central adiposity
      and risk factors for cardiovascular disease. Among Aboriginal and European
      participants, we compared the relation between body mass index and each of the
      following 3 factors: percent body fat, central adiposity and cardiovascular
      disease risk factors. We also compared the relation between waist circumference
      and the same 3 factors. RESULTS: The use of body mass index underestimated
      percent body fat by 1.3% among Aboriginal participants compared with European
      participants (p = 0.025). The use of waist circumference overestimated abdominal
      adipose tissue by 26.7 cm2 among Aboriginal participants compared with European
      participants (p = 0.007). However, there was no difference in how waist
      circumference estimated subcutaneous abdominal and visceral adipose tissue among
      the 2 groups. At the same body mass index and waist circumference, we observed no
      differences in the majority of cardiovascular disease risk factors among
      Aboriginal and European participants. The prevalence of dyslipidemia,
      hypertension, impaired fasting glucose and metabolic syndrome was similar among
      participants in the 2 groups after adjustment for body mass index, waist
      circumference, age and sex. INTERPRETATION: We found no difference in the
      relation between body mass index and risk of cardiovascular disease between men
      and women of Aboriginal and European descent. We also found no difference between
      waist circumference and cardiovascular disease risk among these groups. These
      data support the use of current anthropometric thresholds in the Canadian
      Aboriginal population.

PMID- 18056599
TI  - Parental intention to have daughters receive the human papillomavirus vaccine.
AB  - BACKGROUND: Concerns have been raised that parents may be reluctant to have their
      daughters receive the human papillomavirus (HPV) vaccine, because of a belief
      that doing so might be interpreted as condoning earlier and more frequent sexual
      activity. We determined intentions regarding vaccination among Canadian parents
      and factors that predicted parental intention to have their daughters vaccinated
      against HPV. METHODS: Parents of children 8-18 years of age, recruited from
      across Canada, were asked to respond to questions in the context of a grade 6,
      publicly funded, school-based HPV vaccine program. We performed backward logistic
      regression analysis to identify factors predictive of parents' intention to have
      their daughters vaccinated against HPV. RESULTS: Of the 1350 respondents with
      female children, more than 70% (73.8%; 95% confidence interval [CI] 71.5%-76.1%)
      intended to have their daughters undergo vaccination against HPV. In
      multivariable modelling, parents who had positive attitudes toward vaccines (odds
      ratio [OR] 9.9, 95% CI 4.7-21.1), those who were influenced by subjective norms
      (OR 9.2, 95% CI 6.6-12.9), those who felt that the vaccine had limited influence
      on sexual behaviour (OR 3.2, 95% CI 2.2-4.6) and those who thought someone they
      knew was likely to get cervical cancer (OR 1.5, 95% CI 1.1-2.1) were more likely
      to intend that their daughters receive the HPV vaccine. Parents who were older
      (v. younger) (OR 0.6, 95% CI 0.4-0.8) and those who resided in British Columbia
      or Yukon Territory (v. Atlantic Canada) (OR 0.5, 95% CI 0.3-0.9) were less likely
      to intend that their daughters receive the HPV vaccine. INTERPRETATION: Most of
      the parents surveyed intended that their daughters would receive vaccination
      against HPV. Overall attitudes toward vaccines in general and toward the HPV
      vaccine in particular constituted the most significant predictor of parental
      intention with regard to vaccination.

PMID- 18056600
TI  - Vaccination against human papillomavirus.

PMID- 18056601
TI  - Vaccination against human papillomavirus.

PMID- 18056602
TI  - Vaccination against human papillomavirus.

PMID- 18056603
TI  - Vaccination against human papillomavirus.

PMID- 18056604
TI  - Vaccination against human papillomavirus.

PMID- 18056605
TI  - Vaccination against human papillomavirus.

PMID- 18056611
TI  - Vitamin D deficiency among Italian children.

PMID- 18056616
TI  - A cellular-telephone model of assessing frontal lobe function in physicians.
AB  - As people age, they recognize that social conduct has become worse. This is not
      just a failing of the young but also a reflection of modern technology, notably
      the cellular telephone. We observed that the behaviour induced by the use of such
      devices is so egregious as to be medically informative. We offer a descriptive
      phenomenology and neuroanatomical classification of aberrant behaviour in
      relation to cellular telephone use by physicians at medical conferences. Although
      the cellular telephone is a scourge, its ability to add to the diagnostic
      armamentarium in cognitive neurology should not be overlooked, especially if a
      fee code can be attached.

PMID- 18056617
TI  - One giant leap for mankind? A cost-utility analysis of abolishing the law of
      gravity.
AB  - BACKGROUND: Canada's Neo Rhino Party, a joke political party created in 2006 as a
      successor to the Parti Rhinoceros, is planning a new regulation to repeal the law
      of gravity, which could have an important impact on diseases attributable to
      gravity on earth. METHODS: We sought to estimate the number of quality-adjusted
      life-years that would be saved if the proposed regulation is passed and determine
      the cost-effectiveness of adapting Boris Volfson's antigravity machine for use on
      earth. We performed an economic analysis using a hidden Markov model. RESULTS:
      Our results suggest that a microgravity environment would save over 2 million
      quality-adjusted life-years. The cost for every quality-adjusted life-year saved
      is estimated to be $328. INTERPRETATION: Microgravity is the solution to the
      health care crisis in Canada. In addition, using technological, statistical and
      medical jargon gives us the opportunity to defy the laws of physics, mathematics
      and medicine.

PMID- 18056619
TI  - Exercising privacy rights in medical science.
AB  - Privacy laws are intended to preserve human well-being and improve medical
      outcomes. We used the Sportstats website, a repository of competitive athletic
      data, to test how easily these laws can be circumvented. We designed a haphazard,
      unrepresentative case-series analysis and applied unscientific methods based on
      an Internet connection and idle time. We found it both feasible and titillating
      to breach anonymity, stockpile personal information and generate misquotations.
      We extended our methods to snoop on celebrities, link to outside databases and
      uncover refusal to participate. Throughout our study, we evaded capture and
      public humiliation despite violating these 6 privacy fundamentals. We suggest
      that the legitimate principle of safeguarding personal privacy is undermined by
      the natural human tendency toward showing off.

PMID- 18056618
TI  - A clinical trial gone awry: the Chocolate Happiness Undergoing More Pleasantness
      (CHUMP) study.
AB  - The randomized controlled trial is the "gold standard" for evaluating the
      benefits and harms of interventions. The Chocolate Happiness Undergoing More
      Pleasantness (CHUMP) study was designed to compare the effects of dark chocolate,
      milk chocolate and normal chocolate consumption on happiness. Although the
      intention-to-treat analysis showed that participants who received either dark or
      milk chocolate were happier than those who received no additional chocolate, the
      actual-consumption analysis showed that there were no differences between any of
      the groups. The reason for this result is that many participants switched groups
      mid-study because of their personal chocolate preferences. Although the CHUMP
      study was pleasurable, it demonstrated the difficulties associated with
      performing a truly blinded clinical trial.

PMID- 18056620
TI  - The Goo Tolerance Index: a foolproof method for choosing a medical specialty.

PMID- 18056621
TI  - Sound medicine: an introduction to cacophonology.

PMID- 18056622
TI  - A do-it-yourself stereophonic stethoscope.

PMID- 18056623
TI  - Pondering public health and purity.

PMID- 18056624
TI  - Age at retirement and mortality in a general population sample: the Greek EPIC
      study.
AB  - Investigation of the health effects of retirement and age at retirement is
      limited, but the issue is particularly important given the pressure for an
      increase in the retirement age in Europe. In the Greek segment of the European
      Investigation into Cancer and Nutrition study, 16,827 men and women enrolled from
      1994 to 1999 were either gainfully employed or had retired from such employment
      at enrollment; had not previously been diagnosed with stroke, cancer, coronary
      heart disease, or diabetes mellitus; and had complete information on important
      covariates and documented survival status as of July 2006. All-cause and cause
      specific mortality in relation to employment status and age at retirement (among
      retirees) was analyzed through Cox regression models, controlling for potential
      confounders. In comparison to subjects still employed, retirees had a 51%
      increase in all-cause mortality (95% confidence interval: 16, 98). Among
      retirees, a 5-year increase in age at retirement was associated with a 10%
      decrease in mortality (95% confidence interval: 4, 15). Findings were more
      evident for cardiovascular than for cancer mortality, whereas, for injury
      mortality, there was no evidence of association. Results indicate that early
      retirement may be a risk factor for all-cause and cardiovascular mortality in
      apparently healthy persons.

PMID- 18056625
TI  - Immortal time bias in pharmaco-epidemiology.
AB  - Immortal time is a span of cohort follow-up during which, because of exposure
      definition, the outcome under study could not occur. Bias from immortal time was
      first identified in the 1970s in epidemiology in the context of cohort studies of
      the survival benefit of heart transplantation. It recently resurfaced in pharmaco
      epidemiology, with several observational studies reporting that various
      medications can be extremely effective at reducing morbidity and mortality. These
      studies, while using different cohort designs, all involved some form of immortal
      time and the corresponding bias. In this paper, the author describes various
      cohort study designs leading to this bias, quantifies its magnitude under
      different survival distributions, and illustrates it by using data from a cohort
      of lung cancer patients. The author shows that for time-based, event-based, and
      exposure-based cohort definitions, the bias in the rate ratio resulting from
      misclassified or excluded immortal time increases proportionately to the duration
      of immortal time. The bias is more pronounced with a decreasing hazard function
      for the outcome event, as illustrated with the Weibull distribution compared with
      a constant hazard from the exponential distribution. In conclusion, observational
      studies of drug benefit in which computerized databases are used must be designed
      and analyzed properly to avoid immortal time bias.

PMID- 18056626
TI  - Ultrafine and respirable particles in an automotive grey iron foundry.
AB  - Ultrafine particle number and respirable particle mass concentrations were
      measured throughout an automotive grey iron foundry during winter, spring and
      summer using a particle concentration mapping procedure. Substantial temporal and
      spatial variability was observed in all seasons and attributed, in part, to the
      batch nature of operations, process emission variability and frequent work
      interruptions. The need for fine mapping grids was demonstrated, where elevations
      in particle concentrations were highly localized. Ultrafine particle
      concentrations were generally greatest during winter when incoming make-up air
      was heated with direct fire, natural gas burners. Make-up air drawn from roof
      level had elevated respirable mass and ultrafine number concentrations above
      ambient outdoor levels, suggesting inadvertent recirculation of foundry process
      emissions. Elevated respirable mass concentrations were highly localized on
      occasions (e.g. abrasive blasting and grinding), depended on the area within the
      facility where measurements were obtained, but were largely unaffected by season.
      Particle sources were further characterized by measuring their respective number
      and mass concentrations by particle size. Sources that contributed to ultrafine
      particles included process-specific sources (e.g. melting and pouring
      operations), and non-process sources (e.g. direct fire natural gas heating units,
      a liquid propane-fuelled sweeper and cigarette smoking) were additionally
      identified.

PMID- 18056627
TI  - The preleukemic state of mice reconstituted with Mixl1-transduced marrow cells.
AB  - Murine granulocytic cells, in becoming leukemic, need to acquire enhanced self
      generation and a capacity for autocrine growth stimulation. Mice transplanted
      with bone marrow cells transduced with the Mixl1 homeobox gene develop a very
      high frequency of myeloid leukemia derived from the transduced cells. Preleukemic
      mice contained a high frequency of transduced clonogenic granulocytic cells. They
      exhibited an abnormally high capacity for self-replication and could generate
      immortalized granulocytic cell lines that remained absolutely dependent on either
      GM-CSF or IL-3 and were not leukemic. Organs from mice repopulated by marrow
      cells transduced either with Mixl1 or the control murine stem cell virus vector
      exhibited a capacity to produce IL-3 in vitro, activity being highest with the
      lungs, marrow, bladder, and thymus. Supporting evidence for the in vivo
      production of IL-3 was the frequent development of mast cells in the marrow.
      Overexpression of Mixl1 appears capable of inducing an abnormal self-renewal
      capacity in granulocytic precursors. Aberrant production of IL-3 was not present
      in the continuous Mixl cell lines and was therefore not in itself likely to be a
      leukemogenic change but it could support the enhanced survival and proliferation
      of the Mixl1 granulocytic populations until a final leukemogenic mutation occurs
      in them.

PMID- 18056628
TI  - Two forces for arousal: Pitting hunger versus circadian influences and
      identifying neurons responsible for changes in behavioral arousal.
AB  - The mechanisms underlying CNS arousal in response to homeostatic pressures are
      not known. In this study, we pitted two forces for CNS arousal against each other
      (circadian influences vs. restricted food availability) and measured the neuronal
      activation that occurs in a behaviorally defined group of animals that exhibited
      increased arousal in anticipation of feeding restricted to their normal sleeping
      time. The number of c-FOS+ neurons was significantly increased only in the
      ventromedial nucleus of the hypothalamus (VMH) in these mice, compared with
      control animals whose feeding was restricted to their normal active and feeding
      time (P < 0.01). Because the activation of VMH neurons coincides with the
      earliest signs of behavioral arousal preceding a change in meal time, we infer
      that VMH activation is involved in the increased arousal in anticipation of food.

PMID- 18056629
TI  - Mammary epithelial-specific disruption of the focal adhesion kinase blocks
      mammary tumor progression.
AB  - Elevated expression and activation of the focal adhesion kinase (FAK) occurs in a
      large proportion of human breast cancers. Although several studies have
      implicated FAK as an important signaling molecule in cell culture systems,
      evidence supporting a role for FAK in mammary tumor progression is lacking. To
      directly assess the role of FAK in this process, we have used the Cre/loxP
      recombination system to disrupt FAK function in the mammary epithelium of a
      transgenic model of breast cancer. Using this approach, we demonstrate that FAK
      expression is required for the transition of premalignant hyperplasias to
      carcinomas and their subsequent metastases. This dramatic block in tumor
      progression was further correlated with impaired mammary epithelial
      proliferation. These observations provide direct evidence that FAK plays a
      critical role in mammary tumor progression.

PMID- 18056630
TI  - Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for
      FGFR autoinhibition and activation.
AB  - Mutations in fibroblast growth factor receptor 2 (FGFR2) and its ligand, FGF10,
      are known to cause lacrimo-auriculo-dento-digital (LADD) syndrome. Multiple gain
      of-function mutations in FGF receptors have been implicated in a variety of
      severe skeletal disorders and in many cancers. We aimed to elucidate the
      mechanism by which a missense mutation in the tyrosine kinase domain of FGFR2,
      described in the sporadic case of LADD syndrome, leads to reduced tyrosine kinase
      activity. In this report, we describe the crystal structure of a FGFR2 A628T LADD
      mutant in complex with a nucleotide analog. We demonstrate that the A628T LADD
      mutation alters the configuration of key residues in the catalytic pocket that
      are essential for substrate coordination, resulting in reduced tyrosine kinase
      activity. Further comparison of the structures of WT FGFR2 and WT FGFR1 kinases
      revealed that FGFR2 uses a less stringent mode of autoinhibition than FGFR1,
      which was also manifested in faster in vitro autophosphorylation kinetics.
      Moreover, the nearly identical conformation of WT FGFR2 kinase and the A628T LADD
      mutant to either the phosphorylated FGFR2 or FGFR2 harboring pathological
      activating mutations in the kinase hinge region suggests that FGFR autoinhibition
      and activation are better explained by changes in the conformational dynamics of
      the kinase rather than by static crystallographic snapshots of minor structural
      variations.

PMID- 18056631
TI  - Insulin stimulates the cleavage and release of the extracellular domain of Klotho
      by ADAM10 and ADAM17.
AB  - Cleavage and release (shedding) of membrane proteins is a critical regulatory
      step in many normal and pathological processes. Evidence suggests that the
      antiaging transmembrane protein Klotho (KL) is shed from the cell surface by
      proteolytic cleavage. In this study, we attempted to identify the enzymes
      responsible for the shedding of KL by treating KL-transfected COS-7 cells with a
      panel of proteinase inhibitors and measuring cleavage products by Western blot.
      We report that metalloproteinase inhibitors, including EDTA, EGTA, and TAPI-1,
      inhibit the shedding of KL, whereas insulin increases shedding. The effects of
      the inhibitors in KL-transfected COS-7 cells were repeated in studies on rat
      kidney slices ex vivo, which validates the use of COS-7 cells as our model
      system. Tissue inhibitor of metalloproteinase (Timp)-3 effectively inhibits KL
      cleavage, whereas Timp-1 and Timp-2 do not, a profile that indicates the
      involvement of members of the A Desintegrin and Metalloproteinase (ADAM) family.
      Cotransfection of KL with either ADAM10 or ADAM17 enhances KL cleavage, whereas
      cotransfection of KL with small interference RNAs specific to ADAM10 and ADAM17
      inhibits KL secretion. These results indicate that KL shedding is mediated mainly
      by ADAM10 and ADAM17 in KL-transfected COS-7 cells. The effect of insulin is
      abolished when ADAM10 or ADAM17 are silenced. Furthermore, we demonstrate that
      the effect of insulin on KL shedding is inhibited by wortmannin, showing that
      insulin acts through a PI3K-dependent pathway. Insulin enhances KL shedding
      without increasing ADAM10 and ADAM17 mRNA and protein levels, suggesting that it
      acts by stimulating their proteolytic activities.

PMID- 18056632
TI  - Signal sequence mutation in autosomal dominant form of hypoparathyroidism induces
      apoptosis that is corrected by a chemical chaperone.
AB  - Autosomal dominant familial isolated hypoparathyroidism (AD-FIH) is caused by a
      Cys --> Arg mutation (C18R) in the hydrophobic core of the signal peptide of
      human preproparathyroid hormone (PPTH). Although this mutation impairs secretion
      of the hormone, the mechanism by which one mutant allele produces the autosomal
      dominant disease is unexplained. Using transfected HEK293 cells, we demonstrate
      that the expressed mutant hormone is trapped intracellularly, predominantly in
      the endoplasmic reticulum (ER). This ER retention was found to be toxic for the
      cells, which underwent apoptosis, as evident from the marked increase in the
      number of cells staining positive for Annexin V binding and for the TUNEL
      reaction. The cells producing mutant hormone also had marked up-regulation of the
      ER stress-responsive proteins, BiP and PERK, as well as the proapoptotic
      transcription factor, CHOP. Up-regulation of these markers of the unfolded
      protein response supported a causal link between the ER stress and the cell death
      cascade. When the C18R PPTH was expressed in the presence of 4-phenylbutyric
      acid, which is a pharmacological chaperone, intracellular accumulation was
      reduced and normal secretion was restored. This treatment also produced
      remarkable reduction of ER stress signals and protection against cell death.
      These data implicate ER stress-induced cell death as the underlying mechanism for
      AD-FIH and suggest that the pharmacological manipulation of this pathway by using
      chemical chaperones offers a therapeutic option for treating this disease.

PMID- 18056633
TI  - Trafficking-dependent phosphorylation of Kv1.2 regulates voltage-gated potassium
      channel cell surface expression.
AB  - Kv1.2 alpha-subunits are components of low-threshold, rapidly activating voltage
      gated potassium (Kv) channels in mammalian neurons. Expression and localization
      of Kv channels is regulated by trafficking signals encoded in their primary
      structure. Kv1.2 is unique in lacking strong trafficking signals and in
      exhibiting dramatic cell-specific differences in trafficking, which is suggestive
      of conditional trafficking signals. Here we show that a cluster of cytoplasmic C
      terminal phosphorylation sites regulates Kv1.2 trafficking. Using tandem MS to
      analyze Kv1.2 purified from rat, human, and mouse brain, we identified in each
      sample in vivo phosphoserine (pS) phosphorylation sites at pS434, pS440, and
      pS441, as well as doubly phosphorylated pS440/pS441. We also found these sites,
      as well as pS449, on recombinant Kv1.2 expressed in heterologous cells. We found
      that phosphorylation at pS440/pS441 is present only on the post-endoplasmic
      reticulum (ER)/cell surface pool of Kv1.2 and is not detectable on newly
      synthesized and ER-localized Kv1.2, on which we did observe pS449
      phosphorylation. Elimination of PS440/PS441 phosphorylation by mutation reduces
      cell-surface expression efficiency and functional expression of homomeric Kv1.2
      channels. Interestingly, mutation of S449 reduces phosphorylation at pS440/pS441
      and also decreases Kv1.2 cell-surface expression efficiency and functional
      expression. These mutations also suppress trafficking of Kv1.2/Kv1.4 heteromeric
      channels, suggesting that incorporation of Kv1.2 into heteromeric complexes
      confers conditional phosphorylation-dependent trafficking to diverse Kv channel
      complexes. These data support Kv1.2 phosphorylation at these clustered C-terminal
      sites as playing an important role in regulating trafficking of Kv1.2-containing
      Kv channels.

PMID- 18056634
TI  - Ubiquitin-dependent virus particle budding without viral protein ubiquitination.
AB  - An essential step in the release of an extracellular enveloped virus particle is
      a budding event that ultimately separates virion and host cell membranes. For
      many enveloped viruses, membrane fission requires the recruitment of the class E
      vacuolar protein sorting (VPS) machinery by short, virally encoded peptide
      sequences termed "late-budding" or "L" domains. Some L-domain peptide sequences
      (e.g., PSAP) bind directly to components of class E VPS machinery, whereas others
      (e.g., PPxY) access it indirectly by recruiting ubiquitin ligases. Additionally,
      ubiquitin itself is known to be generally important for the fission of virion
      from cellular membranes, and because ubiquitination of cellular transmembrane
      proteins can signal the recruitment of class E machinery, a popular model is that
      deposition of ubiquitin on viral structural proteins mediates class E machinery
      recruitment. To test this model, we took advantage of a retroviral Gag protein
      from the prototypic foamy virus (PFV) that is almost devoid of ubiquitin
      acceptors, and we engineered it to generate extracellular virus-like particles in
      the complete absence of other viral proteins. Notably, we found that particle
      budding, induced by a class E VPS machinery-binding L domain (PSAP), proceeded
      efficiently in the absence of ubiquitin acceptors in PFV Gag. Moreover, when
      particle release was engineered to be dependent on a viral PPXY motif, the
      requirement for a catalytically active ubiquitin ligase was maintained,
      irrespective of the presence or absence of ubiquitin acceptor sites in PFV Gag.
      Thus, in this model system, ubiquitin conjugation to transacting factors, not
      viral proteins, appears critical for ubiquitin-dependent enveloped viral particle
      release.

PMID- 18056635
TI  - Competitive release and facilitation of drug-resistant parasites after
      therapeutic chemotherapy in a rodent malaria model.
AB  - Malaria infections frequently consist of mixtures of drug-resistant and drug
      sensitive parasites. If crowding occurs, where clonal population densities are
      suppressed by the presence of coinfecting clones, removal of susceptible clones
      by drug treatment could allow resistant clones to expand into the newly vacated
      niche space within a host. Theoretical models show that, if such competitive
      release occurs, it can be a potent contributor to the strength of selection,
      greatly accelerating the rate at which resistance spreads in a population. A
      variety of correlational field data suggest that competitive release could occur
      in human malaria populations, but direct evidence cannot be ethically obtained
      from human infections. Here we show competitive release after pyrimethamine
      curative chemotherapy of acute infections of the rodent malaria Plasmodium
      chabaudi in laboratory mice. The expansion of resistant parasite numbers after
      treatment resulted in enhanced transmission-stage densities. After the
      elimination or near-elimination of sensitive parasites, the number of resistant
      parasites increased beyond that achieved when a competitor had never been
      present. Thus, a substantial competitive release occurred, markedly elevating the
      fitness advantages of drug resistance above those arising from survival alone.
      This finding may explain the rapid spread of drug resistance and the subsequently
      brief useful lifespans of some antimalarial drugs. In a second experiment, where
      subcurative chemotherapy was administered, the resistant clone was only partly
      released from competitive suppression and experienced a restriction in the size
      of its expansion after treatment. This finding raises the prospect of harnessing
      in-host ecology to slow the spread of drug resistance.

PMID- 18056636
TI  - The origin of islet-like cells in Drosophila identifies parallels to the
      vertebrate endocrine axis.
AB  - Single-cell resolution lineage information is a critical key to understanding how
      the states of gene regulatory networks respond to cell interactions and thereby
      establish distinct cell fates. Here, we identify a single pair of neural stem
      cells (neuroblasts) as progenitors of the brain insulin-producing neurosecretory
      cells of Drosophila, which are homologous to islet beta cells. Likewise, we
      identify a second pair of neuroblasts as progenitors of the neurosecretory
      Corpora cardiaca cells, which are homologous to the glucagon-secreting islet
      alpha cells. We find that both progenitors originate as neighboring cells from
      anterior neuroectoderm, which expresses genes orthologous to those expressed in
      the vertebrate adenohypophyseal placode, the source of endocrine anterior
      pituitary and neurosecretory hypothalamic cells [Whitlock KE (2005) Trends
      Endocrinol Metab 16:145-151]. This ontogenic-molecular concordance suggests that
      a rudimentary brain endocrine axis was present in the common ancestor of humans
      and flies, where it orchestrated the islet-like endocrine functions of insulin
      and glucagon biology.

PMID- 18056637
TI  - Anterior temporal lobes mediate semantic representation: mimicking semantic
      dementia by using rTMS in normal participants.
AB  - Studies of semantic dementia and PET neuroimaging investigations suggest that the
      anterior temporal lobes (ATL) are a critical substrate for semantic
      representation. In stark contrast, classical neurological models of comprehension
      do not include ATL, and likewise functional MRI studies often fail to show
      activations in the ATL, reinforcing the classical view. Using a novel application
      of low-frequency, repetitive transcranial magnetic stimulation (rTMS) over the
      ATL, we demonstrate that the behavioral pattern of semantic dementia can be
      mirrored in neurologically intact participants: Specifically, we show that
      temporary disruption to neural processing in the ATL produces a selective
      semantic impairment leading to significant slowing in both picture naming and
      word comprehension but not to other equally demanding, nonsemantic cognitive
      tasks.

PMID- 18056638
TI  - The interplay between the master transcription factor PU.1 and miR-424 regulates
      human monocyte/macrophage differentiation.
AB  - We describe a pathway by which the master transcription factor PU.1 regulates
      human monocyte/macrophage differentiation. This includes miR-424 and the
      transcriptional factor NFI-A. We show that PU.1 and these two components are
      interlinked in a finely tuned temporal and regulatory circuitry: PU.1 activates
      the transcription of miR-424, and this up-regulation is involved in stimulating
      monocyte differentiation through miR-424-dependent translational repression of
      NFI-A. In turn, the decrease in NFI-A levels is important for the activation of
      differentiation-specific genes such as M-CSFr. In line with these data, both RNAi
      against NFI-A and ectopic expression of miR-424 in precursor cells enhance
      monocytic differentiation, whereas the ectopic expression of NFI-A has an
      opposite effect. The interplay among these three components was demonstrated in
      myeloid cell lines as well as in human CD34+ differentiation. These data point to
      the important role of miR-424 and NFI-A in controlling the monocyte/macrophage
      differentiation program.

PMID- 18056639
TI  - A role for the inositol kinase Ipk1 in ciliary beating and length maintenance.
AB  - Cilia project from cells as membranous extensions, with microtubule structural
      cores assembling from basal bodies by intraflagellar transport (IFT). Here, we
      report a ciliary role for the inositol 1,3,4,5,6-pentakisphosphate 2-kinase
      (Ipk1) that generates inositol hexakisphosphate. In zebrafish embryos, reducing
      Ipk1 levels inhibited ciliary beating in Kupffer's vesicle and decreased ciliary
      length in the spinal canal, pronephric ducts, and Kupffer's vesicle. Electron
      microscopy showed that ciliary axonemal structures were not grossly altered.
      However, coincident knockdown of Ipk1 and IFT88 or IFT57 had synergistic
      perturbations. With GFP-Ipk1 enriched in centrosomes and basal bodies, we propose
      that Ipk1 plays a previously uncharacterized role in ciliary function.

PMID- 18056641
TI  - Circuit theory predicts gene flow in plant and animal populations.
AB  - Maintaining connectivity for broad-scale ecological processes like dispersal and
      gene flow is essential for conserving endangered species in fragmented
      landscapes. However, determining which habitats should be set aside to promote
      connectivity has been difficult because existing models cannot incorporate
      effects of multiple pathways linking populations. Here, we test an ecological
      connectivity model that overcomes this obstacle by borrowing from electrical
      circuit theory. The model vastly improves gene flow predictions because it
      simultaneously integrates all possible pathways connecting populations. When
      applied to data from threatened mammal and tree species, the model consistently
      outperformed conventional gene flow models, revealing that barriers were less
      important in structuring populations than previously thought. Circuit theory now
      provides the best-justified method to bridge landscape and genetic data, and
      holds much promise in ecology, evolution, and conservation planning.

PMID- 18056640
TI  - An androgen-regulated miRNA suppresses Bak1 expression and induces androgen
      independent growth of prostate cancer cells.
AB  - Although prostate cancer (CaP) is the most frequently diagnosed malignant tumor
      and the second leading cause of cancer deaths in American men, the mechanisms
      explaining the development and progression of CaP remain largely unknown. Recent
      studies have shown that some aberrantly expressed microRNAs (miRNAs) are involved
      in tumorigenesis. Although aberrant expression of certain miRNAs has been
      discovered in CaP, their function in this disease has not yet been defined. In
      this study, we found differential expression of miR-125b in androgen-dependent
      and independent CaP cells, as well as in benign and malignant prostate tissues.
      Furthermore, androgen signaling was able to up-regulate the expression of miR
      125b. In addition, transfection of synthetic miR-125b stimulated androgen
      independent growth of CaP cells and down-regulated the expression of Bak1. Our
      results suggest that miR-125b acts as an oncogene, contributing to the
      pathogenesis of CaP.

PMID- 18056642
TI  - Hyperpolarized 13C allows a direct measure of flux through a single enzyme
      catalyzed step by NMR.
AB  - (13)C NMR is a powerful tool for monitoring metabolic fluxes in vivo. The recent
      availability of automated dynamic nuclear polarization equipment for
      hyperpolarizing (13)C nuclei now offers the potential to measure metabolic fluxes
      through select enzyme-catalyzed steps with substantially improved sensitivity.
      Here, we investigated the metabolism of hyperpolarized [1-(13)C(1)]pyruvate in a
      widely used model for physiology and pharmacology, the perfused rat heart.
      Dissolved (13)CO(2), the immediate product of the first step of the reaction
      catalyzed by pyruvate dehydrogenase, was observed with a temporal resolution of
      approximately 1 s along with H(13)CO(3)(-), the hydrated form of (13)CO(2)
      generated catalytically by carbonic anhydrase. In hearts presented with the
      medium-chain fatty acid octanoate in addition to hyperpolarized [1
      (13)C(1)]pyruvate, production of (13)CO(2) and H(13)CO(3)(-) was suppressed by
      approximately 90%, whereas the signal from [1-(13)C(1)]lactate was enhanced. In
      separate experiments, it was shown that O(2) consumption and tricarboxylic acid
      (TCA) cycle flux were unchanged in the presence of added octanoate. Thus, the
      rate of appearance of (13)CO(2) and H(13)CO(3)(-) from [1-(13)C(1)]pyruvate does
      not reflect production of CO(2) in the TCA cycle but rather reflects flux through
      pyruvate dehydrogenase exclusively.

PMID- 18056644
TI  - Observational evidence for volcanic impact on sea level and the global water
      cycle.
AB  - It has previously been noted that there are drops in global sea level (GSL) after
      some major volcanic eruptions. However, observational evidence has not been
      convincing because there is substantial variability in the global sea level
      record over periods similar to those at which we expect volcanoes to have an
      impact. To quantify the impact of volcanic eruptions we average monthly GSL data
      from 830 tide gauge records around five major volcanic eruptions. Surprisingly,
      we find that the initial response to a volcanic eruption is a significant rise in
      sea level of 9 +/- 3 mm in the first year after the eruption. This rise is
      followed by a drop of 7 +/- 3 mm in the period 2-3 years after the eruption
      relative to preeruption sea level. These results are statistically robust and no
      particular volcanic eruption or ocean region dominates the signature we find.
      Neither the drop nor especially the rise in GSL can be explained by models of
      lower oceanic heat content. We suggest that the mechanism is a transient
      disturbance of the water cycle with a delayed response of land river runoff
      relative to ocean evaporation and global precipitation that affects global sea
      level. The volcanic impact on the water cycle and sea levels is comparable in
      magnitude to that of a large El Nino-La Nina cycle, amounting to approximately 5%
      of global land precipitation.

PMID- 18056643
TI  - Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific
      tyrosine phosphatase implicated in autoimmune diseases.
AB  - The lymphoid-specific tyrosine phosphatase (Lyp) has generated enormous interest
      because a single-nucleotide polymorphism in the gene (PTPN22) encoding Lyp
      produces a gain-of-function mutant phosphatase that is associated with several
      autoimmune diseases, including type I diabetes, rheumatoid arthritis, Graves
      disease, and systemic lupus erythematosus. Thus, Lyp represents a potential
      target for a broad spectrum of autoimmune disorders. Unfortunately, no Lyp
      inhibitor has been reported. In addition, little is known about the structure and
      biochemical mechanism that directly regulates Lyp function. Here, we report the
      identification of a bidentate salicylic acid-based Lyp inhibitor I-C11 with
      excellent cellular efficacy. Structural and mutational analyses indicate that the
      inhibitor binds both the active site and a nearby peripheral site unique to Lyp,
      thereby furnishing a solid foundation upon which inhibitors with therapeutic
      potency and selectivity can be developed. Moreover, a comparison of the apo- and
      inhibitor-bound Lyp structures reveals that the Lyp-specific region
      S(35)TKYKADK(42), which harbors a PKC phosphorylation site, could adopt either a
      loop or helical conformation. We show that Lyp is phosphorylated exclusively at
      Ser-35 by PKC both in vitro and in vivo. We provide evidence that the status of
      Ser-35 phosphorylation may dictate the conformational state of the insert region
      and thus Lyp substrate recognition. We demonstrate that Ser-35 phosphorylation
      impairs Lyp's ability to inactivate the Src family kinases and down-regulate T
      cell receptor signaling. Our data establish a mechanism by which PKC could
      attenuate the cellular function of Lyp, thereby augmenting T cell activation.

PMID- 18056645
TI  - Perennial stream discharge in the hyperarid Atacama Desert of northern Chile
      during the latest Pleistocene.
AB  - A large fraction of the vital groundwater in the Atacama Desert of northern Chile
      is likely composed of "fossil" or "ancient" reserves that receive little or no
      recharge in today's hyperarid climate. Here, we present evidence for latest
      Pleistocene perennial streamflow in canyons from the hyperarid core of the
      Atacama Desert in northern Chile. Fluvial terraces in the Pampa del Tamarugal
      (PdT) basin (21 degrees S) contain widespread fossil wood, in situ roots, and
      well preserved leaf litter deposits indicative of perennial surface flow
      currently absent in these channels. Nineteen radiocarbon dates on these deposits
      from four separate drainages within this endorheic basin indicate ages from
      16,380 to 13,740 cal yr BP, synchronous with paleolake Tauca on the Bolivian
      Altiplano and other regional evidence for wetter conditions during the latest
      Pleistocene. Groundwater-fed riparian ecosystems and associated fluvial deposits
      abound today in the absence of direct rainfall in northern Atacama canyons with
      perennial discharge. Our relict riparian ecosystems from the PdT basin are
      indicative of conditions similar to these northern canyons. Given that discharge
      was higher than present during this time, we propose that these deposits
      represent the most important groundwater recharge events of the last 18,000
      years. A lesser recharge event occurred during the Holocene, when phreatophytic
      trees also grew in these drainages between 1,070 and 700 cal yr BP, during the
      Medieval Climatic Anomaly. Taken together, our evidence lends further support for
      gradient changes in the equatorial Pacific as a major driver of hydrologic change
      in the Atacama on both centennial and millennial time scales.

PMID- 18056646
TI  - Pseudomonas syringae type III effector AvrRpt2 alters Arabidopsis thaliana auxin
      physiology.
AB  - The Pseudomonas syringae type III effector AvrRpt2 promotes bacterial virulence
      on Arabidopsis thaliana plants lacking a functional RPS2 gene (rps2 mutant
      plants). To investigate the mechanisms underlying the virulence activity of
      AvrRpt2, we examined the phenotypes of transgenic A. thaliana rps2 seedlings
      constitutively expressing AvrRpt2. These seedlings exhibited phenotypes
      reminiscent of A. thaliana mutants with altered auxin physiology, including
      longer primary roots, increased number of lateral roots, and increased
      sensitivity to exogenous auxin. They also had increased levels of free indole
      acetic acid (IAA). The presence of AvrRpt2 also was correlated with a further
      increase in free IAA levels during infection with P. syringae pv. tomato strain
      DC3000 (PstDC3000). These results indicate that AvrRpt2 alters A. thaliana auxin
      physiology. Application of the auxin analog 1-naphthaleneacetic acid promoted
      disease symptom development in PstDC3000-infected plants, suggesting that
      elevated auxin levels within host tissue promote PstDC3000 virulence. Thus,
      AvrRpt2 may be among the virulence factors of P. syringae that modulate host
      auxin physiology to promote disease.

PMID- 18056647
TI  - Recruitment of conjugative DNA transfer substrate to Agrobacterium type IV
      secretion apparatus.
AB  - Bacterial type IV secretion system (T4SS) belongs to a growing class of
      evolutionarily conserved transporters that translocate DNA and proteins into a
      wide variety of organisms including bacterial and eukaryotic cells. Archetypal is
      the Agrobacterium tumefaciens VirB/D4 T4SS that transfers oncogenic T-DNA to
      various eukaryotic cells, which is transferred as a nucleoprotein T-complex with
      VirD2 as the pilot protein. As a derivative of plasmid conjugation systems, the
      VirB/D4 T4SS can also transfer certain mobilizable plasmids and bacterial
      proteins like VirE2 and VirF, although it is unknown how the membrane-bound T4SS
      recruits different transfer substrates. Here, we show that a cytoplasmic VirD2
      binding protein (VBP) is involved in the recruitment of the T-complex to the
      energizing components of the T4SS, including VirD4, VirB4, and VirB11. VBP is
      also important for the recruitment of a conjugative plasmid to a different
      transfer system independent of VirB/D4. These data indicate that VBP functions as
      a previously unrecognized recruiting protein that helps couple nucleoprotein
      substrates to the appropriate transport sites for conjugative DNA transfers. VBP
      has three functionally redundant homologs, and similar homologs can be found in
      different bacterial genomes, suggesting a previously uncharacterized class of
      proteins involved in conjugative DNA transfers.

PMID- 18056648
TI  - A phase II study of sorafenib in patients with chemo-naive castration-resistant
      prostate cancer.
AB  - BACKGROUND: The purpose of this trial was to evaluate the antitumor activity of
      sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, in
      patients with castration-resistant prostate cancer. PATIENTS AND METHODS: This
      was a multicenter, two-stage, phase II study. Sorafenib 400 mg was administered
      orally twice daily continuously. Primary end point was prostate-specific antigen
      (PSA) 'response' defined as a > or =50% decrease for > or =4 weeks. RESULTS: In
      all, 28 patients were enrolled. Eastern Cooperative Oncology Group performance
      status was zero or one in 19 and 9 patients. Two patients had no metastases, and
      26 had bone and/or lymph node disease. A median of two cycles (range 1-8) was
      delivered. Adverse events were typical for sorafenib. The PSA response rate was
      3.6% [95% confidence interval (CI) 0.1% to 18.3%] with response occurring in one
      patient (baseline = 10 000 and nadir = 1643 microg/l). No measurable disease
      responses occurred in eight patients. Time to PSA progression was 2.3 months (95%
      CI 1.8-6.4). Of 16 patients who discontinued sorafenib and then did not receive
      any immediate therapy, 10 had postdiscontinuation PSA declines of 7%-52%.
      CONCLUSIONS: Sorafenib has limited activity using current PSA criteria. The
      declines in PSA observed on treatment discontinuation indicate an effect on PSA
      production/secretion. Further study may be warranted but needs to consider the
      limitations of PSA as an indicator of progression and response.

PMID- 18056649
TI  - The impact of follicular lymphoma on health-related quality of life.
AB  - BACKGROUND: The purpose of this study was to determine whether there was a
      relationship between disease activity and health functioning, as measured by a
      range of patient-reported outcome (PRO) measures in patients with follicular
      lymphoma (FL). PATIENTS AND METHODS: A total of 222 patients with FL were
      recruited from eight sites across the UK and they completed a number of PRO
      measures. The participants were analyzed across five disease states: 'active
      disease-newly diagnosed', 'active disease-relapsed', 'partial response',
      'complete response' and 'disease free'. The relationship between these disease
      states and their level of health functioning was assessed as well as the
      relationship between being 'on' or 'off' chemotherapy and disease state. RESULTS:
      In terms of health-related quality of life (HRQoL), participants in the relapsed
      category had the lowest mean physical well-being, emotional well-being,
      functional well-being and social well-being score. In a regression analysis, the
      'active disease-relapsed' group acted as a significant predictor for each PRO
      variable. In addition, the remission group acted as a significant predictor of
      high anxiety scores as measured by the Hospital Anxiety and Depression Scale.
      CONCLUSION: The results of this study demonstrate that various aspects of patient
      reported health outcomes differ according to disease state in patients with FL.
      For those patients who have relapsed, they are more likely to experience worse
      HRQoL and other patient-reported health outcomes than patients newly diagnosed,
      in partial or complete remission or when completely disease free.

PMID- 18056650
TI  - Compassionate use of bevacizumab (Avastin) in children and young adults with
      refractory or recurrent solid tumors.
AB  - BACKGROUND: The aim of this study was to evaluate feasibility and toxicity of
      bevacizumab (Avastin), a monoclonal antibody directed against the vascular
      endothelial growth factor in children and young adults. PATIENTS AND METHODS:
      Fifteen patients (male: n = 8; female: n = 7; median age, 14.6 years) received
      bevacizumab for recurrent or progressive solid tumors (carcinoma: n = 3;
      neuroblastoma: n = 2; astrocytoma grade III: n = 2; rhabdomyosarcoma: n = 2;
      nephroblastoma: n = 2; benign vascular tumors: n = 2; synovial sarcoma: n = 1;
      and malignant hemangiopericytoma: n = 1) on a compassionate basis. Bevacizumab
      was administered at 5-10 mg/kg body weight intravenously every 2-3 weeks. Most
      patients received chemotherapy in addition to bevacizumab. Duration of
      bevacizumab therapy ranged from 1.5 to 23 months. RESULTS: Bevacizumab-related
      side-effects were mild and included hypertonia (n = 2), proteinuria/hematuria (n
      = 2), epistaxis (n = 2), local erythema (n = 1), and defective wound healing and
      ascites (n = 1). Radiographic objective responses (partial responses) were
      observed in two patients with astrocytoma grade III and in one patient each with
      neuroblastoma and pleomorphic rhabdomyosarcoma, respectively. CONCLUSIONS:
      Bevacizumab seems to have a good acute safety profile and some antitumor activity
      in heavily pretreated children and young adults with recurrent solid tumors.
      Prospective clinical trials are urgently needed to further evaluate the safety
      and efficacy of bevacizumab in pediatric patients.

PMID- 18056651
TI  - Sensitive detection of isoglobo and globo series tetraglycosylceramides in human
      thymus by ion trap mass spectrometry.
AB  - Glycosphingolipids serve as ligands for receptors involved in signal transduction
      and immune recognition, as exemplified by isoglobotrihexosylceramide, an
      antigenic ligand for T cell receptors. Mechanistic studies on the regulation of
      isoglobotrihexosylceramide require biochemical measurement of its lysosomal
      precursor, isoglobotetraglycosylceramide. It remains a challenge to distinguish
      between complex tetraglycosylceramide glycosphingolipid isomers with the same
      sugar components but diverse internal linkages. Here we established a simple and
      sensitive method to separate globo- and isoglobotetraglycosylceramide by MS5 ion
      trap mass spectrometry, and report the identification of
      isoglobotetraglycosylceramide in a CHO cell line transfected by iGb3 synthase, as
      well as in human thymus.

PMID- 18056652
TI  - Neural complex-specific expression of xylosyl N-glycan in Ciona intestinalis.
AB  - We herein report N-glycosylation profiles of the individual tissues derived from
      the ascidian Ciona intestinalis. Multidimensional HPLC mapping revealed that the
      C. intestinalis expresses high-mannose-type oligosaccharides as major N-glycans,
      along with paucimannose-type and complex-type oligosaccharides, in a tissue
      specific manner. Notably, the trimannosyl core carrying beta1,2-xylose and
      alpha1,3-fucose residues was identified as a principal N-glycan in the neural
      complex. As far as we know, this is the first description of xylosyl N-glycan
      expressed in deuterostome. Furthermore, we found that this xylosyl N-glycan is
      exclusively displayed on a membrane-associated protein so far described as a
      putative protein whose gene expression is specific for the neural complex. These
      data suggested that the xylosyl N-glycan is associated with some neural functions
      of C. intestinalis.

PMID- 18056653
TI  - Learning from the health care systems of other countries.

PMID- 18056654
TI  - Achieving a high-performance health care system with universal access: what the
      United States can learn from other countries.
AB  - This position paper concerns improving health care in the United States. Unlike
      previous highly focused policy papers by the American College of Physicians, this
      article takes a comprehensive approach to improving access, quality, and
      efficiency of care. The first part describes health care in the United States.
      The second compares it with health care in other countries. The concluding
      section proposes lessons that the United States can learn from these countries
      and recommendations for achieving a high-performance health care system in the
      United States. The articles are based on a position paper developed by the
      American College of Physicians' Health and Public Policy Committee. This policy
      paper (not included in this article) also provides a detailed analysis of health
      care systems in 12 other industrialized countries. Although we can learn much
      from other health systems, the College recognizes that our political and social
      culture, demographics, and form of government will shape any solution for the
      United States. This caution notwithstanding, we have identified several
      approaches that have worked well for countries like ours and could probably be
      adapted to the unique circumstances in the United States.

PMID- 18056655
TI  - Summaries for patients. Emergency department visits for adverse drug events in
      older adults.

PMID- 18056657
TI  - Summaries for patients. Screening for high blood pressure: U.S. Preventive
      Services Task Force recommendation.

PMID- 18056656
TI  - Summaries for patients. Risk for fatal pulmonary embolism after discontinuing
      anticoagulation.

PMID- 18056658
TI  - In the Clinic. Heart failure.

PMID- 18056659
TI  - Medication use leading to emergency department visits for adverse drug events in
      older adults.
AB  - BACKGROUND: The Beers criteria identify inappropriate use of medications in older
      adults. The number of and risk for adverse events from these medications are
      unknown. OBJECTIVE: To estimate the number of and risk for emergency department
      visits for adverse events involving Beers criteria medications compared with
      other medications. DESIGN: Nationally representative, public health surveillance
      of adverse drug events and a cross-sectional survey of outpatient medical visits.
      SETTING: National Electronic Injury Surveillance System-Cooperative Adverse Drug
      Event Surveillance System, 2004-2005; National Ambulatory Medical Care Survey,
      2004; and National Hospital Ambulatory Medical Care Survey, 2004. PARTICIPANTS:
      Persons 65 years of age or older seeking emergency department and outpatient
      care. MEASUREMENTS: Estimated number of and risks for emergency department visits
      for adverse drug events involving Beers criteria medications and other
      medications. RESULTS: Among U.S. patients 65 years of age or older, an estimated
      177,504 emergency department visits (95% CI, 100,155 to 254,854 visits) for
      adverse drug events occurred both years. An estimated 3.6% (CI, 2.8% to 4.5%) of
      these visits were for adverse events medications considered to be always
      potentially inappropriate, according to the Beers criteria, and 33.3% (CI, 27.8%
      to 38.7%) of visits were for adverse events from 3 other medications (warfarin
      [17.3%], insulin [13.0%], and digoxin [3.2%]). Accounting for outpatient
      prescription frequency, the risk for emergency department visits for adverse
      events due to these 3 medications was 35 times (CI, 9.6 to 61) greater than that
      for medications considered to be always potentially inappropriate. LIMITATION:
      Adverse events were identified only in emergency departments. CONCLUSION:
      Compared with other medications, Beers criteria medications caused low numbers of
      and few risks for emergency department visits for adverse events. Performance
      measures and interventions targeting warfarin, insulin, and digoxin use could
      prevent more emergency department visits for adverse events.

PMID- 18056660
TI  - The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy
      for venous thromboembolism.
AB  - BACKGROUND: The long-term risk for fatal pulmonary embolism (PE) after treatment
      of venous thromboembolism (VTE) may be an important factor in the decision to
      discontinue this treatment. OBJECTIVE: To provide reliable and precise estimates
      of the annual risk for fatal PE and the case-fatality rate of disease recurrence
      and to assess these outcomes according to the initial presentation of VTE (deep
      venous thrombosis [DVT], PE, or both) and its etiology (secondary or idiopathic)
      in patients who have discontinued anticoagulant therapy. DESIGN: Prospective
      cohort study. SETTING: Academic medical centers. PATIENTS: Inception cohort of
      patients with a first episode of symptomatic VTE who discontinued anticoagulant
      therapy. MEASUREMENTS: Incidence rates of any fatal PE (which included sudden
      death from possible fatal PE) and definite or probable PE per 100 person-years of
      follow-up and case-fatality rate of recurrent VTE. RESULTS: Of 2052 patients
      studied, 1450 had DVT, 310 had PE, and 292 had DVT and PE. The mean duration of
      previous anticoagulant therapy was 6 months (range, 3 to 39 months), and the mean
      duration of follow-up after discontinuation of treatment was 54 months (range, 1
      to 120 months). The annual risk for any fatal PE and definite or probable fatal
      PE after discontinuation of anticoagulation was 0.49 events (95% CI, 0.36 to 0.64
      events) per 100 person-years and 0.19 events (CI, 0.12 to 0.30 events) per 100
      person-years, respectively. The case-fatality rate of recurrent disease was 9.0%
      (CI, 6.8% to 11.8%) for any fatal PE and 3.8% (CI, 2.4% to 5.9%) for definite or
      probable fatal PE. LIMITATION: The findings are less pertinent to patients with
      active cancer, permanent immobility, or high-risk thrombophilia. CONCLUSION: The
      risk for fatal PE is 0.19 to 0.49 events per 100 person-years for patients who
      have finished a course of anticoagulant therapy for a first episode of
      symptomatic VTE. The case-fatality rate for death from recurrent PE is 4% to 9%.
      This information helps to inform patient prognosis and may assist clinicians in
      deciding whether to discontinue anticoagulant therapy for VTE.

PMID- 18056661
TI  - Update in oncology.

PMID- 18056662
TI  - Screening for high blood pressure: U.S. Preventive Services Task Force
      reaffirmation recommendation statement.
AB  - DESCRIPTION: Reaffirmation of the 2003 U.S. Preventive Services Task Force
      statement about screening for high blood pressure. METHODS: The U.S. Preventive
      Services Task Force did a targeted literature search for evidence on the benefits
      and harms of screening for high blood pressure. RECOMMENDATION: Screen for high
      blood pressure in adults age 18 years or older. (Grade A recommendation).

PMID- 18056663
TI  - Evidence for the reaffirmation of the U.S. Preventive Services Task Force
      recommendation on screening for high blood pressure.
AB  - BACKGROUND: High blood pressure is common, and screening is a well-established
      evidence-based standard of current medical practice. PURPOSE: To perform a
      literature search for new, substantial evidence on screening for high blood
      pressure that would inform the reaffirmation of the U.S. Preventive Services Task
      Force recommendation on screening for high blood pressure. DATA SOURCES: The
      PubMed and Cochrane databases were searched. The searches were limited to English
      language articles on studies of adult humans (age >18 years) that were published
      between 1 October 2001 and 31 March 2006 in core clinical journals. STUDY
      SELECTION: For the literature on benefits, meta-analyses; systematic reviews; and
      randomized, controlled trials were included. For harms, meta-analyses; systematic
      reviews; randomized, controlled trials; cohort studies; case-control studies; and
      case series of large, multisite databases were included. Two reviewers
      independently reviewed titles, abstracts, and full articles for inclusion. DATA
      EXTRACTION: No new evidence was found on benefits or harms of screening. Two
      reviewers extracted data from studies on the harms of early treatment, including
      adverse effects of drug therapy and adverse quality-of-life outcomes. DATA
      SYNTHESIS: No new evidence was found for the benefits of screening for high blood
      pressure. New evidence on the harms of treatment of early hypertension shows that
      pharmacologic therapy is associated with common side effects; serious adverse
      events are uncommon. LIMITATIONS: The nonsystematic search may have missed some
      smaller studies on the benefits and harms of screening and treatment for high
      blood pressure. CONCLUSION: No new evidence was found on the benefits of
      screening. Pharmacotherapy for early hypertension is associated with common side
      effects.

PMID- 18056664
TI  - Pay-for-performance principles that promote patient-centered care: an ethics
      manifesto.
AB  - Pay-for-performance programs are growing, but little evidence exists on their
      effectiveness or on their potential unintended consequences and effects on the
      patient-physician relationship. Pay-for-performance has the potential to help
      improve the quality of care, if it can be aligned with the goals of medical
      professionalism. Initiatives that provide incentives for a few specific elements
      of a single disease or condition, however, may neglect the complexity of care for
      the whole patient, especially the elderly patient with multiple chronic
      conditions. Such programs could also result in the deselection of patients,
      "playing to the measures" rather than focusing on the patient as a whole, and
      misalignment of perceptions between physicians and patients. The primary focus of
      the quality movement in health care should not be on "pay for" or "performance"
      based on limited measures, but rather on the patient. The American College of
      Physicians hopes to move the pay-for-performance debate forward with a patient
      centered focus--one that puts the needs and interests of the patient first--as
      these programs evolve.

PMID- 18056665
TI  - Professionalism in medicine: results of a national survey of physicians.
AB  - BACKGROUND: The prospect of improving care through increasing professionalism has
      been gaining momentum among physician organizations. Although there have been
      efforts to define and promote professionalism, few data are available on
      physician attitudes toward and conformance with professional norms. OBJECTIVE: To
      ascertain the extent to which practicing physicians agree with and act
      consistently with norms of professionalism. DESIGN: National survey using a
      stratified random sample. SETTING: Medical care in the United States.
      PARTICIPANTS: 3504 practicing physicians in internal medicine, family practice,
      pediatrics, surgery, anesthesiology, and cardiology. MEASUREMENTS: Attitudes and
      behaviors were assessed by using indicators for each domain of professionalism
      developed by the American College of Physicians and the American Board of
      Internal Medicine. Of the eligible sampled physicians, 1662 responded, yielding a
      58% weighted response rate (adjusting for noneligible physicians). RESULTS:
      Ninety percent or more of the respondents agreed with specific statements about
      principles of fair distribution of finite resources, improving access to and
      quality of care, managing conflicts of interest, and professional self
      regulation. Twenty-four percent disagreed that periodic recertification was
      desirable. Physician behavior did not always reflect the standards they endorsed.
      For example, although 96% of respondents agreed that physicians should report
      impaired or incompetent colleagues to relevant authorities, 45% of respondents
      who encountered such colleagues had not reported them. LIMITATIONS: Our measures
      of behavior did not capture all activities that may reflect on the norms in
      question. Furthermore, behaviors were self-reported, and the results may not be
      generalizable to physicians in specialties not included in the study. CONCLUSION:
      Physicians agreed with standards of professional behavior promulgated by
      professional societies. Reported behavior, however, did not always conform to
      those norms.

PMID- 18056666
TI  - Ventilator-associated pneumonia--the wrong quality measure for benchmarking.
AB  - Legislators, payers, and quality-of-care advocates across the United States are
      considering requiring hospitals to report ventilator-associated pneumonia rates
      as a way to benchmark and reward quality of care. Accurate diagnosis of
      ventilator-associated pneumonia, however, is notoriously difficult because
      several common complications of critical care can mimic the clinical appearance
      of ventilator-associated pneumonia. The challenge is compounded by substantial
      subjectivity inherent in the current surveillance definition. These sources of
      variability make ventilator-associated pneumonia rates difficult to acquire,
      interpret, and compare both within and among institutions. Ventilator-associated
      pneumonia should be excluded from compulsory reporting initiatives until we
      develop and validate more objective outcome measures that meaningfully reflect
      quality of care for ventilated patients.

PMID- 18056667
TI  - Evolution of therapy for chronic hepatitis B: progressing from the simple to the
      complex.

PMID- 18056668
TI  - Medical professionalism and the parable of the craft guilds.

PMID- 18056669
TI  - An uneasy understanding.

PMID- 18056670
TI  - Risks of intravenous immunoglobulin in sepsis affect trial design.

PMID- 18056671
TI  - The declining number and variety of procedures done by general internists.

PMID- 18056672
TI  - The declining number and variety of procedures done by general internists.

PMID- 18056673
TI  - The declining number and variety of procedures done by general internists.

PMID- 18056674
TI  - The declining number and variety of procedures done by general internists.

PMID- 18056675
TI  - Strategies for timely and effective hospice discussions: end-stage renal disease.

PMID- 18056676
TI  - Pharmacogenetics of efavirenz: adherence and virologic outcomes.

PMID- 18056677
TI  - Protein biomarker identification in the CSF of patients with CNS lymphoma.
AB  - PURPOSE: Elucidation of the CSF proteome may yield insights into the pathogenesis
      of CNS disease. We tested the hypothesis that individual CSF proteins distinguish
      CNS lymphoma from benign focal brain lesions. METHODS: We used a liquid
      chromatography/mass spectrometry-based method to differentially quantify and
      identify several hundred CSF proteins in CNS lymphoma and control patients. We
      used enzyme-linked immunosorbent assay (ELISA) to confirm one of these markers in
      an additional validation set of 101 cases. RESULTS: Approximately 80 CSF proteins
      were identified and found to be present at significantly different
      concentrations, both higher and lower, in training and test studies, which were
      highly concordant. To further validate these observations, we defined in detail
      the expression of one of these candidate biomarkers, antithrombin III (ATIII).
      ATIII RNA transcripts were identified within CNS lymphomas, and ATIII protein was
      localized selectively to tumor neovasculature. Determination of ATIII
      concentration by ELISA was significantly more accurate (> 75% sensitivity; > 98%
      specificity) than cytology in the identification of cancer. Measurement of CSF
      ATIII levels was found to potentially enhance the ability to diagnose and predict
      outcome. CONCLUSION: Our findings demonstrate for the first time that proteomic
      analysis of CSF yields individual biomarkers with greater sensitivity in the
      identification of cancer than does CSF cytology. We propose that the discovery of
      CSF protein biomarkers will facilitate early and noninvasive diagnosis in
      patients with lesions not amenable to brain biopsy, as well as provide improved
      surrogates of prognosis and treatment response in CNS lymphoma and brain
      metastasis.

PMID- 18056678
TI  - Stem-cell transplantation for multiple myeloma in the era of novel drugs.
AB  - The treatment of multiple myeloma (MM) is changing rapidly. During the last 10
      years, higher rates of complete response (CR) and prolonged progression-free and
      overall survival have been seen with high-dose chemotherapy plus autologous stem
      cell transplantation (HDT-ASCT). Achievement of CR and good partial response have
      been shown to be key prognostic factors for prolonged survival, with eradication
      of minimal residual disease seeming crucial to long-term disease-free survival.
      Until recently, high rates of CR and other major responses were primarily seen
      with HDT-ASCT, but insights into the biology of MM have led to the development
      and approval of new drugs with significant activity, and new induction regimens
      based on these novel agents are offering improved responses. Thalidomide,
      bortezomib, and lenalidomide have been combined with corticosteroids, alkylators,
      and anthracyclines in front-line MM treatment. Phase II studies have indicated
      that high rates of response and CR may be achieved. The substantial activity seen
      with these new drug combinations has prompted a re-examination of the role of SCT
      in MM treatment. Will achievement of major responses with these new regimens
      translate into improved survival after consolidation with transplantation? Will
      these improved induction regimens reduce the need for tandem transplantation, or
      does achievement of CR obviate the need for front-line transplantation
      altogether? To help address these questions, randomized trials are needed, as
      well as tests with improved sensitivity to better define depth of remission.

PMID- 18056679
TI  - Nonmyeloablative allogeneic hematopoietic cell transplantation in relapsed,
      refractory, and transformed indolent non-Hodgkin's lymphoma.
AB  - PURPOSE: Few effective treatment options exist for chemotherapy-refractory
      indolent or transformed non-Hodgkin's lymphoma (NHL). We examined the outcome of
      nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in this
      setting. PATIENTS AND METHODS: Sixty-two patients with indolent or transformed
      NHL were treated with allogeneic HCT from related (n = 34) or unrelated (n = 28)
      donors after conditioning with 2 Gy of total-body irradiation with or without
      fludarabine. Nine unrelated donors were mismatched for >/= one HLA antigen.
      Sixteen patients had histologic transformation before HCT. Twenty patients (32%)
      had progressive disease after previous high-dose therapy with autologous HCT.
      Median age was 54 years, and patients had received a median of six lines of
      treatment before HCT. Median follow-up time after HCT was 36.6 months. RESULTS:
      At 3 years, the estimated overall survival (OS) and progression-free survival
      (PFS) rates were 52% and 43%, respectively, for patients with indolent disease,
      and 18% and 21%, respectively, for patients with transformed disease. Patients
      with indolent disease and related donors (n = 26) had 3-year estimated OS and PFS
      rates of 67% and 54%, respectively. The incidences of grade 2 to 4 acute graft
      versus-host disease (GVHD), grade 3 and 4 acute GVHD, and extensive chronic GVHD
      were 63%, 18%, and 47%, respectively. Among survivors, the median Karnofsky
      performance status at last follow-up was 85%. CONCLUSION: Nonmyeloablative
      allogeneic HCT can produce durable disease-free survival in patients with
      relapsed or refractory indolent NHL, even in this relatively elderly and heavily
      pretreated cohort. Outcomes were particularly good in patients with untransformed
      disease and related donors, whereas patients with transformed disease did poorly.
      Long-term survivors reported good overall functional status.

PMID- 18056680
TI  - Combined use of clinical and pathologic staging variables to define outcomes for
      breast cancer patients treated with neoadjuvant therapy.
AB  - PURPOSE: Neoadjuvant chemotherapy is being used with increasing frequency for
      operable breast cancer. We hypothesized that by using clinical and pathologic
      staging parameters, in conjunction with biologic tumor markers, a novel means of
      determining prognosis for patients treated with neoadjuvant chemotherapy could be
      facilitated. PATIENTS AND METHODS: A prospective database of patients treated
      with neoadjuvant chemotherapy from 1997 to 2003 was reviewed, and 932 patients
      meeting inclusion criteria were identified. Clinical and pathologic tumor
      characteristics, treatment regimens, and patient outcomes were recorded. Cox
      proportional hazards models were used to create two prognostic scoring systems.
      American Joint Committee on Cancer (AJCC) clinical and pathologic staging
      parameters and biologic tumor markers were investigated to devise the scoring
      systems. RESULTS: Median follow-up time was 5 years (range, 0.4 to 9.4 years).
      Five-year disease-specific survival rate was 96% for patients who experienced a
      pathologic complete response (pCR; n = 130) compared with 87% for patients who
      did not have a pCR (n = 802; P = .001). Two scoring systems, based on summing
      binary indicators for clinical substages >/= IIB and >/= IIIB, pathologic
      substages >/= ypIIA and >/= ypIIIC, negative estrogen receptor status, and grade
      3 pathology, were devised to predict 5-year patient outcomes. These scoring
      systems facilitated separation of the study population into more refined
      subgroups by outcome than the current AJCC staging system. CONCLUSION: The
      scoring systems derived in this work provide a novel means for evaluating
      prognosis after neoadjuvant therapy. Future work will focus on prospective
      validation of these scoring systems and refinement of the scoring systems through
      addition of new biologic markers.

PMID- 18056681
TI  - Large-scale appearance of ultraconserved elements in tetrapod genomes and
      slowdown of the molecular clock.
AB  - Mammalian genomes contain millions of highly conserved noncoding sequences, many
      of which are regulatory. The most extreme examples are the 481 ultraconserved
      elements (UCEs) that are identical over at least 200 bp in human, mouse, and rat
      and show 96% identity with chicken, which diverged approximately 310 MYA. If the
      substitution rate in UCEs remained constant, these elements should also be
      present with a high level of identity in fish (approximately 450 Myr), but this
      is not the case, suggesting that many appeared in the amniotes or tetrapods or
      that the molecular clock has slowed down in these lineages, or both. Taking
      advantage of the availability of multiple genomes, we identified 13,736 UCEs in
      the human genome that are identical over at least 100 bp in at least 3 of 5
      placental mammals, including 2,189 sequences over at least 200 bp, thereby
      greatly expanding the repertoire of known UCEs, and investigated the evolution of
      these sequences in opossum, chicken, frog, and fish. We conclude that there was a
      massive genome-wide acquisition and expansion of UCEs during tetrapod and then
      amniote evolution, accompanied by a slowdown of the molecular clock, particularly
      in the amniotes, a process consistent with their functional exaptation in these
      lineages. The majority of tetrapod-specific UCEs are noncoding and associated
      with genes involved in regulation of transcription and development. In contrast,
      fish genomes contain relatively few UCEs, the majority of which are common to all
      bony vertebrates. These elements are different from other conserved noncoding
      elements and appear to be important regulatory innovations that became fixed
      following the emergence of vertebrates from the sea to the land.

PMID- 18056682
TI  - Commentary on Alex Cohen et al: "Questioning an axiom: better prognosis for
      schizophrenia in the developing world".

PMID- 18056683
TI  - A common VLDLR polymorphism interacts with APOE genotype in the prediction of
      carotid artery disease risk.
AB  - The genetic factors associated with carotid artery disease (CAAD) are not fully
      known. Because of its role in lipid metabolism, we hypothesized that common
      genetic variation in the very low density lipoprotein receptor (VLDLR) gene is
      associated with severe CAAD (>80% stenosis), body mass index (BMI), and lipid
      traits in humans. VLDLR was resequenced for variation discovery in 92 subjects,
      and single nucleotide polymorphisms (tagSNPs) were chosen for genotyping in a
      larger cohort (n = 1,027). Of the 17 tagSNPs genotyped, one tagSNP (SNP 1226;
      rs1454626) located in the 5' flanking region of VLDLR was associated with CAAD,
      BMI, and LDL-associated apolipoprotein B (apoB). We also identified receptor
      ligand genetic interactions between VLDLR 1226 and APOE genotype for predicting
      CAAD case status. These findings may further our understanding of VLDLR function,
      its ligand APOE, and ultimately the pathogenesis of CAAD in the general
      population.

PMID- 18056684
TI  - An apolipoprotein A-I mimetic dose-dependently increases the formation of
      prebeta1 HDL in human plasma.
AB  - Prebeta1 HDL is the initial plasma acceptor of cell-derived cholesterol in
      reverse cholesterol transport. Recently, small amphipathic peptides composed of D
      amino acids have been shown to mimic apolipoprotein A-I (apoA-I) as a precursor
      for HDL formation. ApoA-I mimetic peptides have been proposed to stimulate the
      formation of prebeta1 HDL and increase reverse cholesterol transport in apoE-null
      mice. The existence of a monoclonal antibody (MAb 55201) and a corresponding
      ELISA method that is selective for the detection of the prebeta(1) subclass of
      HDL provides a means of establishing a correlation between apoA-I mimetic dose
      and prebeta1 HDL formation in human plasma. Using this prebeta1 HDL ELISA, we
      demonstrate marked apoA-I mimetic dose-dependent prebeta1 HDL formation in human
      plasma. These results correlated with increases in band density of the plasma
      prebeta1 HDL, when observed by Western blotting, as a function of increased apoA
      I mimetic concentration. Increased prebeta1 HDL formation was observed after as
      little as 1 min and was maximal within 1 h. Together, these data suggest that a
      high-throughput prebeta1 HDL ELISA provides a way to quantitatively measure a key
      component of the reverse cholesterol transport pathway in human plasma, thus
      providing a possible method for the identification of apoA-I mimetic molecules.

PMID- 18056685
TI  - Effect of apolipoprotein A-V on plasma triglyceride, lipoprotein size, and
      composition in genetically engineered mice.
AB  - Transgenic (Tg) mice that overexpress the human apolipoprotein A-V gene (APOA5)
      yet lack an endogenous mouse apoa5 gene (APOA5 Tg mice) were generated.
      Subsequently, the effect of human apoA-V expression on plasma triglyceride (TG)
      concentration and lipoprotein and apolipoprotein distribution was determined and
      compared with that in mice deficient in apoA-V (apoa5(-/-) mice). NMR analysis of
      plasma lipoproteins revealed that APOA5 Tg mice had a very low VLDL concentration
      (26.4 +/- 7.7 nmol/dl), whereas VLDL in apoa5(-/-) mice was 18- fold higher (467
      +/- 152 nmol/dl). SDS-PAGE analysis of the d < 1.063 g/ml plasma fraction
      revealed that the apoB-100/apoB-48 ratio was 14-fold higher in APOA5 Tg versus
      apoa5(-/-) mice and that the apoE/total apoB ratio was 7-fold greater in APOA5 Tg
      versus apoa5(-/-) mice. It is anticipated that a reduction in apoB-100/apoB-48
      ratio as well as that for apoE/apoB would impair the uptake of VLDL and remnants
      in apoa5(-/-) mice, thereby contributing to increased plasma TG levels. The
      concentration of apoA-V in APOA5 Tg mice was 12.5 +/- 2.9 microg/ml, which is
      approximately 50- to 100-fold higher than that reported for normolipidemic
      humans. ApoA-V was predominantly associated with HDL but was rapidly and
      efficiently redistributed to apoA- V-deficient VLDL upon incubation. Consistent
      with findings reported for human subjects, apoA-V concentration was positively
      correlated with TG levels in normolipidemic APOA5 Tg mice. It is conceivable
      that, in a situation in which apoA-V is chronically overexpressed, complex
      interactions among factors regulating TG homeostasis may result in a positive
      correlation of apoA-V with TG concentrations.

PMID- 18056686
TI  - Predicting renal graft failure using multivariate longitudinal profiles.
AB  - Patients who have undergone renal transplantation are monitored longitudinally at
      irregular time intervals over 10 years or more. This yields a set of biochemical
      and physiological markers containing valuable information to anticipate a failure
      of the graft. A general linear, generalized linear, or nonlinear mixed model is
      used to describe the longitudinal profile of each marker. To account for the
      correlation between markers, the univariate mixed models are combined into a
      multivariate mixed model (MMM) by specifying a joint distribution for the random
      effects. Due to the high number of markers, a pairwise modeling strategy, where
      all possible pairs of bivariate mixed models are fitted, is used to obtain
      parameter estimates for the MMM. These estimates are used in a Bayes rule to
      obtain, at each point in time, the prognosis for long-term success of the
      transplant. It is shown that allowing the markers to be correlated can improve
      this prognosis.

PMID- 18056687
TI  - Robust combination of multiple diagnostic tests for classifying censored event
      times.
AB  - Recent advancement in technology promises to yield a multitude of tests for
      disease diagnosis and prognosis. When there are multiple sources of information
      available, it is often of interest to construct a composite score that can
      provide better classification accuracy than any individual measurement. In this
      paper, we consider robust procedures for optimally combining tests when test
      results are measured prior to disease onset and disease status evolves over time.
      To account for censoring of disease onset time, the most commonly used approach
      to combining tests to detect subsequent disease status is to fit a proportional
      hazards model (Cox, 1972) and use the estimated risk score. However, simulation
      studies suggested that such a risk score may have poor accuracy when the
      proportional hazards assumption fails. We propose the use of a nonparametric
      transformation model (Han, 1987) as a working model to derive an optimal
      composite score with theoretical justification. We demonstrate that the proposed
      score is the optimal score when the model holds and is optimal "on average" among
      linear scores even if the model fails. Time-dependent sensitivity, specificity,
      and receiver operating characteristic curve functions are used to quantify the
      accuracy of the resulting composite score. We provide consistent and
      asymptotically Gaussian estimators of these accuracy measures. A simple model
      free resampling procedure is proposed to obtain all consistent variance
      estimators. We illustrate the new proposals with simulation studies and an
      analysis of a breast cancer gene expression data set.

PMID- 18056689
TI  - Rett syndrome: recent research progress.
AB  - Recent progress in our understanding of Rett syndrome has been dramatic. Against
      the background that the clinical features of Rett syndrome may be reversible, in
      part or in whole, substantial optimism has emerged regarding possible therapies.
      As such, it is timely to update recent research progress. This update summarizes
      research advances during the past 18 to 24 months in terms of clinical and
      translational research, as well as basic research.

PMID- 18056690
TI  - Cognitive and psychological profile of males with Becker muscular dystrophy.
AB  - Duchenne and Becker muscular dystrophy are allelic X-linked disorders causing
      progressive muscle weakness in males. Duchenne muscular dystrophy is caused by
      absence of dystrophin in muscle and brain; boys with Duchenne muscular dystrophy
      have a static cognitive impairment with mean Full Scale IQ approximately 1
      standard deviation below the mean. Less is known of the cognitive profile of
      males with Becker muscular dystrophy, which is associated with variable
      alterations in the amount or size of the dystrophin protein. The aim of this
      study was to describe the cognitive and psychological profile of males with
      Becker muscular dystrophy. This was a prospective cohort study. Clinical data
      collected included age at diagnosis and assessment, socioeconomic status, serum
      creatine kinase level, and site of gene deletion/mutation (by exon number). The
      following psychological tests were used to assess general intellectual
      functioning, academic achievement, incidence and nature of behavioral problems:
      The Wechsler Intelligence Scales, The Wide Range Achievement Test-Revised, The
      Developmental Test of Visual-Motor Integration, The Child Behavior Checklist, and
      The Conner's Parent Rating Scale. Twenty-four males were enrolled. The Wechsler
      Full Scale IQ was normally distributed with a mean of 95.6 (SD 23.3), which did
      not differ significantly from the population mean. The frequency of learning
      difficulties for reading was 21%, for spelling was 32%, and for arithmetic was
      26%, significantly higher than the frequency in the general population. The
      frequency of total behavioral problems in the clinical range was 67%, and the
      frequency of autism was 8.3%. Patients with Becker muscular dystrophy demonstrate
      a less homogeneous cognitive phenotype than that seen in Duchenne muscular
      dystrophy. Males with Becker muscular dystrophy have a high incidence of learning
      difficulties. Autism and behavioral and attention problems are also more common
      in Becker muscular dystrophy than in the general population.

PMID- 18056688
TI  - Transcranial magnetic stimulation in child neurology: current and future
      directions.
AB  - Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation
      based on the principle of electromagnetic induction, where small intracranial
      electric currents are generated by a powerful, rapidly changing extracranial
      magnetic field. Over the past 2 decades TMS has shown promise in the diagnosis,
      monitoring, and treatment of neurological and psychiatric disease in adults, but
      has been used on a more limited basis in children. We reviewed the literature to
      identify potential diagnostic and therapeutic applications of TMS in child
      neurology and also its safety in pediatrics. Although TMS has not been associated
      with any serious side effects in children and appears to be well tolerated,
      general safety guidelines should be established. The potential for applications
      of TMS in child neurology and psychiatry is significant. Given its excellent
      safety profile and possible therapeutic effect, this technique should develop as
      an important tool in pediatric neurology over the next decade.

PMID- 18056691
TI  - Autism spectrum disorders: concurrent clinical disorders.
AB  - Individuals with autism spectrum disorder are heterogeneous in clinical
      presentation, concurrent disorders, and developmental outcomes. This study
      characterized the clinical co-occurrences and potential subgroups in 160 children
      with autism spectrum disorders who presented to The Autism Center between 1999
      and 2003. Medical and psychiatric co-occurrences included sleep disorders,
      epilepsy, food intolerance, gastrointestinal dysfunction, mood disorder, and
      aggressive and self-injurious behaviors. Sleep disorders were associated with
      gastrointestinal dysfunction (P < .05) and mood disorders (P < .01). Food
      intolerance was associated with gastrointestinal dysfunction (P = .001). Subjects
      with mood disorder tended to develop aggressive or self-injurious behaviors (P <
      .05). Developmental regression was not associated with increased co-occurrence of
      medical or psychiatric disorders. Medical co-occurrence did not present as a risk
      factor for psychiatric co-occurrence, and vice versa. These results showed a high
      prevalence of multiple medical and psychiatric co-occurrences. There may be
      common pathophysiologic mechanisms resulting in clinical subgroups of autism
      spectrum disorders. Recognition of the co-occurrence of concurrent disorders may
      provide insight into the therapeutic strategy.

PMID- 18056692
TI  - Partial trisomy of 7q: case report and literature review.
AB  - This case describes a boy with pure partial trisomy of the long arm of chromosome
      7. The only prenatal finding on the boy was cerebral ventricular enlargement.
      After birth, mild facial dysmorphic features and cardiac malformations (pulmonary
      valve dysplasia, interatrial and interventricular septal defects) were detected.
      The boy developed severe psychomotor retardation, failure to thrive, and poor
      interaction with the environment. Focal seizures occurred in the neonatal period.
      Left frontotemporal abnormalities were observed in the subsequent
      electroencephalograms. An area of subependymal nodular heterotopia in the right
      frontal region was detected. Eighteen cases of 7q pure trisomy have been
      described in the literature over the years. The present study confirms that, in
      7q trisomy cases, there are several common, yet nonspecific, features:
      macrocephaly, frontal bossing, failure to thrive, psychomotor delay, low-set
      ears, short neck, and genital-urinary tract abnormalities. Shortened life span
      seems associated only with duplication of the entire arm, and correlation
      phenotype-genotype seems questionable.

PMID- 18056693
TI  - Transcranial Doppler ultrasound in children with Sturge-Weber syndrome.
AB  - Transcranial Doppler ultrasound is a noninvasive vascular assessment technique
      proved useful in the management of pediatric disorders predisposed to stroke and
      may have similar utility for Sturge-Weber syndrome. Eight children with Sturge
      Weber syndrome had velocities measured in the major cerebral arteries via the
      Stroke Prevention Trial in Sickle Cell Anemia methodology. Velocities and
      pulsatility indexes were compared between the unaffected and affected sides. All
      subjects had reduced velocity on the affected side; the mean middle cerebral
      artery percentage difference was 20% (95% CI, 15%-25%). Pulsatility index was
      increased on the affected side; mean middle cerebral artery pulsatility index
      percentage difference, 34% (95% CI, 15%-53%). Six subjects also had reduced
      posterior cerebral artery velocity on the affected side. Side-to-side differences
      in middle cerebral artery and posterior cerebral artery velocities correlated
      with severity of MRI asymmetry (Spearman rho = 0.88, P = .02). Decreased arterial
      flow velocity and increased pulsatility index in the middle cerebral artery and
      posterior cerebral artery suggests a high resistance pattern that may reflect
      venous stasis and may contribute to chronic hypoperfusion of brain tissue.
      Further study of Transcranial Doppler in children with Sturge-Weber syndrome is
      indicated.

PMID- 18056694
TI  - Juvenile onset central nervous system folate deficiency and rheumatoid arthritis.
AB  - Isolated cerebral folate deficiency was detected in a 13-year-old girl with
      cognitive and motor difficulties and juvenile rheumatoid arthritis. Her serum
      contains autoantibodies that block membrane-bound folate receptors that are on
      the choroid plexus and diminish the uptake of folate into the spinal fluid.
      Whereas her serum folate exceeded 21 ng/mL, her spinal fluid contained 3.2 ng/mL
      of 5-methyltetrahydrofolate as a consequence of the autoantibodies diminishing
      the uptake of this folate.

PMID- 18056695
TI  - Endoscopic management of hydrocephalus in pediatric patients: a review of
      indications, techniques, and outcomes.
AB  - Although ventriculoperitoneal shunting remains the treatment of choice for many
      children with hydrocephalus, advances in endoscopic technology have greatly
      expanded the treatment options for these patients. For selected patients with
      obstructive hydrocephalus, endoscopic third ventriculostomy and other endoscopic
      techniques offer substantial advantages over shunting. As with any surgical
      procedure, appropriate patient selection is critical to successful outcomes. This
      article reviews modern endoscopic techniques available to treat hydrocephalus,
      with a focus on selection criteria and outcomes.

PMID- 18056696
TI  - Prevalence and outcome of congenital heart disease in patients with neural tube
      defect.
AB  - A prospective clinical study was designed to establish the risk factors, the
      prevalence, and the progress of congenital heart defects in children with neural
      tube defects. Study included 90 children with a mean age of 13.5 +/- 30.4 months.
      There were 53 (59%) patients with spina bifida occulta and 37 (41%) patients with
      spina bifida aperta. The overall prevalence of congenital heart disease was 27.8%
      (40.5% in spina bifida aperta and 18.9% in spina bifida occulta; P = .024). There
      was no statistically significant difference for maternal age, usage of
      periconceptional folate, and maternal diabetes between the patient and control
      groups. The authors conclude that congenital heart defects are more common than
      reported in neural tube defects, and screening echocardiograms are warranted.
      This should be kept in mind especially in patients requiring minor or major
      surgical procedures. Furthermore, routine obstetric examination and therefore the
      use of periconceptional folic acid during pregnancy is still lacking in our
      country.

PMID- 18056697
TI  - Male-to-female transsexuals show sex-atypical hypothalamus activation when
      smelling odorous steroids.
AB  - One working hypothesis behind transsexuality is that the normal sex
      differentiation of certain hypothalamic networks is altered. We tested this
      hypothesis by investigating the pattern of cerebral activation in 12
      nonhomosexual male-to-female transsexuals (MFTRs) when smelling 4,16-androstadien
      3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST). These steroids are
      reported to activate the hypothalamic networks in a sex-differentiated way. Like
      in female controls the hypothalamus in MFTRs activated with AND, whereas smelling
      of EST engaged the amygdala and piriform cortex. Male controls, on the other
      hand, activated the hypothalamus with EST. However, when restricting the volume
      of interest to the hypothalamus activation was detected in MFTR also with EST,
      and explorative conjunctional analysis revealed that MFTR shared a hypothalamic
      cluster with women when smelling AND, and with men when smelling EST. Because the
      EST effect was limited, MFTR differed significantly only from male controls, and
      only for EST-AIR and EST-AND. These data suggest a pattern of activation away
      from the biological sex, occupying an intermediate position with predominantly
      female-like features. Because our MFTRs were nonhomosexual, the results are
      unlikely to be an effect of sexual practice. Instead, the data implicate that
      transsexuality may be associated with sex-atypical physiological responses in
      specific hypothalamic circuits, possibly as a consequence of a variant neuronal
      differentiation.

PMID- 18056698
TI  - Effects of working memory load on oscillatory power in human intracranial EEG.
AB  - Studies of working memory load effects on human EEG power have indicated
      divergent effects in different frequency bands. Although gamma power typically
      increases with load, the load dependency of the lower frequency theta and alpha
      bands is uncertain. We obtained intracranial electroencephalography measurements
      from 1453 electrode sites in 14 epilepsy patients performing a Sternberg task, in
      order to characterize the anatomical distribution of load-related changes across
      the frequency spectrum. Gamma power increases occurred throughout the brain, but
      were most common in the occipital lobe. In the theta and alpha bands, both
      increases and decreases were observed, but with different anatomical
      distributions. Increases in theta and alpha power were most prevalent in frontal
      midline cortex. Decreases were most commonly observed in occipital cortex,
      colocalized with increases in the gamma range, but were also detected in lateral
      frontal and parietal regions. Spatial overlap with group functional magnetic
      resonance imaging results was minimal except in the precentral gyrus. These
      findings suggest that power in any given frequency band is not a unitary
      phenomenon; rather, reactivity in the same frequency band varies in different
      brain regions, and may relate to the engagement or inhibition of a given area in
      a cognitive task.

PMID- 18056699
TI  - Functional organization of temporal frequency selectivity in primate visual
      cortex.
AB  - Several studies have shown that neurons with similar response properties are
      arranged together in domains across primary visual cortex (V1). An orderly
      pattern of domains has been described for preferences to ocular dominance,
      orientation, and spatial frequency. Temporal frequency preference, another
      important attribute of the visual scene, also might be expected to map into
      different domains. Using optical imaging and a variety of quantitative methods,
      we examined how temporal frequency selectivity is mapped in V1 of the prosimian
      primate, bush baby (Otolemur garnetti). We found that unlike other attribute
      maps, selectivity for different temporal frequencies is arranged uniformly across
      V1 with no evidence of local clustering. Global tuning for temporal frequency,
      based on magnitude of response, showed a good match to previous tuning curves for
      single neurons. A peak response was found around 2.0 Hz, with smaller attenuation
      at lower temporal frequencies than at higher frequencies. We also examined
      whether the peak temporal frequency response differed between anatomical
      compartments defined by cytochrome oxidase (CO). No significant differences in
      the preference for temporal frequency were found between these CO compartments.
      Our findings show that key sensory attributes that are linked in perception can
      be organized in quite distinct ways in V1 of primates.

PMID- 18056700
TI  - Evidence that a mutation in the MLH1 3'-untranslated region confers a mutator
      phenotype and mismatch repair deficiency in patients with relapsed leukemia.
AB  - Defects in DNA mismatch repair (MMR) are the molecular basis of certain cancers,
      including hematological malignancies. The defects are often caused by mutations
      in coding regions of MMR genes or promoter methylation of the genes. However, in
      many cases, despite that a hypermutable phenotype is detected in a patient, no
      mutations/hypermethylations of MMR genes can be detected. We report here a novel
      mechanism that a mutation in the MLH1 3'-untranslated region (3'-UTR) leads to
      MMR deficiency. A relapsed leukemia patient displayed microsatellite instability,
      but no genetic and epigenetic alterations in key MMR genes were identifiable.
      Instead, a 3-nucleotide (TTC) deletion in the MLH1 3'-UTR was found in the
      patient's blood sample. The mutant MLH1 3'-UTR was found to significantly reduce
      the expressions of both a firefly luciferase reporter gene and an ectopic MLH1
      gene in model cell lines. Consistent with these observations, a significant
      reduction in the steady-state level of MLH1 mRNA was observed in white blood
      cells of the patient. These findings suggest that the mutant MLH1 3'-UTR can
      cause a severely reduced/defective MMR activity conferring leukemia relapse,
      likely by down-regulating MLH1 expression at the mRNA level. Although the exact
      mechanism by which the mutant 3'-UTR down-regulates the MLH1 mRNA is not known,
      our findings provide a novel marker for cancers with MMR defects.

PMID- 18056701
TI  - Paraquat neurotoxicity is mediated by a Bak-dependent mechanism.
AB  - Paraquat (PQ) causes selective degeneration of dopaminergic neurons in the
      substantia nigra pars compacta, reproducing an important pathological feature of
      Parkinson disease. Oxidative stress, c-Jun N-terminal kinase activation, and
      alpha-synuclein aggregation are each induced by PQ, but details of the cell death
      mechanisms involved remain unclear. We have identified a Bak-dependent cell death
      mechanism that is required for PQ-induced neurotoxicity. PQ induced morphological
      and biochemical features that were consistent with apoptosis, including dose
      dependent cytochrome c release, with subsequent caspase-3 and poly(ADP-ribose)
      polymerase cleavage. Changes in nuclear morphology and loss of viability were
      blocked by cycloheximide, caspase inhibitor, and Bcl-2 overexpression. Evaluation
      of Bcl-2 family members showed that PQ induced high levels of Bak, Bid, BNip3,
      and Noxa. Small interfering RNA-mediated knockdown of BNip3, Noxa, and Bak each
      protected cells from PQ, but Bax knockdown did not. Finally, we tested the
      sensitivity of Bak-deficient mice and found them to be resistant to PQ treatments
      that depleted tyrosine hydroxylase immuno-positive neurons in the substantia
      nigra pars compacta of wild-type mice.

PMID- 18056702
TI  - NF-kappaB-inducing kinase phosphorylates and blocks the degradation of Down
      syndrome candidate region 1.
AB  - Down syndrome, the most frequent genetic disorder, is characterized by an extra
      copy of all or part of chromosome 21. Down syndrome candidate region 1 (DSCR1)
      gene, which is located on chromosome 21, is highly expressed in the brain of Down
      syndrome patients. Although its cellular function remains unknown, DSCR1
      expression is linked to inflammation, angiogenesis, and cardiac development. To
      explore the functional role of DSCR1 and the regulation of its expression, we
      searched for novel DSCR1-interacting proteins using a yeast two-hybrid assay.
      Using a human fetal brain library, we found that DSCR1 interacts with NF-kappaB
      inducing kinase (NIK). Furthermore, we demonstrate that NIK specifically
      interacts with and phosphorylates the C-terminal region of DSCR1 in immortalized
      hippocampal cells as well as in primary cortical neurons. This NIK-mediated
      phosphorylation of DSCR1 increases its protein stability and blocks its
      proteasomal degradation, the effects of which lead to an increase in soluble and
      insoluble DSCR1 levels. We show that an increase in insoluble DSCR1 levels
      results in the formation of cytosolic aggregates. Interestingly, we found that
      whereas the formation of these inclusions does not significantly alter the
      viability of neuronal cells, the overexpression of DSCR1 without the formation of
      aggregates is cytotoxic.

PMID- 18056703
TI  - Neurotrophic activity of neudesin, a novel extracellular heme-binding protein, is
      dependent on the binding of heme to its cytochrome b5-like heme/steroid-binding
      domain.
AB  - Neudesin is a secreted protein with neurotrophic activity in neurons and
      undifferentiated neural cells. We report here that neudesin is an extracellular
      heme-binding protein and that its neurotrophic activity is dependent on the
      binding of heme to its cytochrome b(5)-like heme/steroid-binding domain. At
      first, we found that at least a portion of the purified recombinant neudesin
      appeared to bind hemin because the purified neudesin solution was tinged with
      green and had a sharp absorbance peak at 402 nm. The addition of exogenous hemin
      extensively increased the amount of hemin-bound neudesin. In contrast,
      neudesinDeltaHBD, a mutant lacking the heme-binding domain, could not bind hemin.
      The neurotrophic activity of the recombinant neudesin that bound exogenous hemin
      (neudesin-hemin) was significantly greater than that of the recombinant neudesin
      in either primary cultured neurons or Neuro2a cells, suggesting that the activity
      of neudesin depends on hemin. The neurotrophic activity of neudesin was enhanced
      by the binding of Fe(III)-protoporphyrin IX, but neither Fe(II)-protoporphyrin IX
      nor protoporphyrin IX alone. The inhibition of endogenous neudesin by RNA
      interference significantly decreased cell survival in Neuro2a cells. This
      indicates that endogenous neudesin possibly contains hemin. The experiment with
      anti-neudesin antibody suggested that the endogenous neudesin detected in the
      culture medium of Neuro2a cells was associated with hemin because it was not
      retained on a heme-affinity column at all. Neudesin is the first extracellular
      heme-binding protein that shows signal transducing activity by itself. The
      present findings may shed new light on the function of extracellular heme-binding
      proteins.

PMID- 18056704
TI  - mTORC1 signaling can regulate growth factor activation of p44/42 mitogen
      activated protein kinases through protein phosphatase 2A.
AB  - The mTORC1 complex (mammalian target of rapamycin (mTOR)-raptor) is modulated by
      mitogen-activated protein (p44/42 MAP) kinases (p44/42) through phosphorylation
      and inactivation of the tuberous sclerosis complex. However, a role for mTORC1
      signaling in modulating activation of p44/42 has not been reported. We show that
      in two cancer cell lines regulation of the p44/42 MAPKs is mTORC1-dependent. In
      Rh1 cells rapamycin inhibited insulin-like growth factor-I (IGF-I)-stimulated
      phosphorylation of Thr(202) but not Tyr(204) and suppressed activation of p44/42
      kinase activity. Down-regulation of raptor, which inhibits mTORC1 signaling, had
      a similar effect to rapamycin in blocking IGF-I-stimulated Tyr(204)
      phosphorylation. Rapamycin did not block maximal phosphorylation of Tyr(204) but
      retarded the rate of dephosphorylation of Tyr(204) following IGF-I stimulation.
      IGF-I stimulation of MEK1 phosphorylation (Ser(217/221)) was not inhibited by
      rapamycin. Higher concentrations of rapamycin (> or =100 ng/ml) were required to
      inhibit epidermal growth factor (EGF)-induced phosphorylation of p44/42
      (Thr(202)). Rapamycin-induced inhibition of p44/42 (Thr(202)) phosphorylation by
      IGF-I was reversed by low concentrations of okadaic acid, suggesting involvement
      of protein phosphatase 2A (PP2A). Both IGF-I and EGF caused dissociation of PP2A
      catalytic subunit (PP2Ac) from p42. Whereas low concentrations of rapamycin (1
      ng/ml) inhibited dissociation of PP2Ac after IGF-I stimulation, it required
      higher concentrations (> or =100 ng/ml) to block EGF-induced dissociation,
      consistent with the ability for rapamycin to attenuate growth factor-induced
      activation of p44/42. The effect of rapamycin on IGF-I or insulin activation of
      p44/42 was recapitulated by amino acid deprivation. Rapamycin effects altering
      the kinetics of p44/42 phosphorylation were completely abrogated in Rh1mTORrr
      cells that express a rapamycin-resistant mTOR, whereas the effects of amino acid
      deprivation were similar in Rh1 and Rh1mTORrr cells. These results indicate
      complex regulation of p44/42 by phosphatases downstream of mTORC1. This suggests
      a model in which mTORC1 modulates the phosphorylation of Thr(202) on p44/42 MAPKs
      through direct or indirect regulation of PP2Ac.

PMID- 18056705
TI  - Activation of AMP-activated protein kinase induces p53-dependent apoptotic cell
      death in response to energetic stress.
AB  - Tumor suppressor p53-dependent stress response pathways play an important role in
      cell fate determination. In this study, we have found that glucose depletion
      promotes the phosphorylation of AMP-activated protein kinase catalytic subunit
      alpha (AMPKalpha) in association with a significant up-regulation of p53, thereby
      inducing p53-dependent apoptosis in vivo and in vitro. Thymocytes prepared from
      glucose-depleted wild-type mice but not from p53-deficient mice underwent
      apoptosis, which was accompanied by a remarkable phosphorylation of AMPKalpha and
      a significant induction of p53 as well as pro-apoptotic Bax. Similar results were
      also obtained in human osteosarcoma-derived U2OS cells bearing wild-type p53
      following glucose starvation. Of note, glucose deprivation led to a significant
      accumulation of p53 phosphorylated at Ser-46, but not at Ser-15 and Ser-20, and a
      transcriptional induction of p53 as well as proapoptotic p53 AIP1. Small
      interference RNA-mediated knockdown of p53 caused an inhibition of apoptosis
      following glucose depletion. Additionally, apoptosis triggered by glucose
      deprivation was markedly impaired by small interference RNA-mediated depletion of
      AMPKalpha. Under our experimental conditions, down-regulation of AMPKalpha caused
      an attenuation of p53 accumulation and its phosphorylation at Ser-46. In support
      of these observations, enforced expression of AMPKalpha led to apoptosis and
      resulted in an induction of p53 at protein and mRNA levels. Furthermore, p53
      promoter region responded to AMPKalpha and glucose deprivation as judged by
      luciferase reporter assay. Taken together, our present findings suggest that AMPK
      dependent transcriptional induction and phosphorylation of p53 at Ser-46 play a
      crucial role in the induction of apoptosis under carbon source depletion.

PMID- 18056706
TI  - Regulation of FynT function by dual domain docking on PAG/Cbp.
AB  - In resting T-cells, the transmembrane adaptor protein PAG (phosphoprotein
      associated with glycosphingolipid-enriched microdomains) is constitutively
      tyrosine-phosphorylated, a state maintained by the Src family kinase FynT. PAG
      has a role in negative regulation of Src family kinases in T-cells by recruitment
      of Csk (C-terminal Src kinase) to the membrane via binding to PAG phosphotyrosine
      317. The interaction between FynT and PAG is essential for PAG function; however,
      so far the FynT binding mode has been unknown. Here, we demonstrate that the FynT
      PAG complex formation is a dual domain docking process, involving SH2 domain
      binding to PAG phosphotyrosines as well as an SH3 domain interaction with the
      first proline-rich region of PAG. This binding mode affects FynT kinase activity,
      PAG phosphorylation, and recruitment of FynT and Csk, demonstrated in Jurkat TAg
      cells after antibody stimulation of the T cell receptor. Furthermore, we show
      that TCR-induced tyrosine phosphorylation is regulated by SH3 domain modulation
      of the FynT-PAG interaction in human primary T-cells. Although FynT SH3 domain
      association is shown to be crucial for efficiently initiating PAG
      phosphorylation, we suggest that engagement of the SH2 domain on PAG renders FynT
      insensitive to Csk negative regulation. Thus, in T-cells, PAG is involved in
      positive as well as negative regulation of FynT activity.

PMID- 18056707
TI  - Activator protein-1 contributes to high NaCl-induced increase in tonicity
      responsive enhancer/osmotic response element-binding protein transactivating
      activity.
AB  - Tonicity-responsive enhancer/osmotic response element-binding protein
      (TonEBP/OREBP) is a Rel protein that activates transcription of osmoprotective
      genes at high extracellular NaCl. Other Rel proteins NFAT1-4 and NF-kappaB
      complex with activator protein-1 (AP-1) to transactivate target genes through
      interaction at composite NFAT/NF-kappaB.AP-1 sites. TonEBP/OREBP target genes
      commonly have one or more conserved AP-1 binding sites near TonEBP/OREBP cognate
      elements (OREs). Also, TonEBP/OREBP and the AP-1 proteins c-Fos and c-Jun are all
      activated by high NaCl. We now find, using an ORE.AP-1 reporter from the target
      aldose reductase gene or the same reporter with a mutated AP-1 site, that upon
      stimulation by high extracellular NaCl, 1) the presence of a wild type, but not a
      mutated, AP-1 site contributes to TonEBP/OREBP-dependent transcription and 2) AP
      1 dominant negative constructs inhibit TonEBP/OREBP-dependent transcription
      provided the AP-1 site is not mutated. Using supershifts and an ORE.AP-1 probe,
      we find c-Fos and c-Jun present in combination with TonEBP/OREBP. Also, c-Fos and
      c-Jun coimmunoprecipitate with TonEBP/OREBP, indicating physical association.
      Small interfering RNA knockdown of either c-Fos or c-Jun inhibits high NaCl
      induced increase of mRNA abundance of the TonEBP/OREBP target genes AR and BGT1.
      Furthermore, a dominant negative AP-1 also reduces high NaCl-induced increase of
      TonEBP/OREBP transactivating activity. Inhibition of p38, which is known to
      stimulate TonEBP/OREBP transcriptional activity, reduces high NaCl-dependent
      transcription of an ORE.AP-1 reporter only if the AP-1 site is intact. Thus, AP-1
      is part of the TonEBP/OREBP enhanceosome, and its role in high NaCl-induced
      activation of TonEBP/OREBP may require p38 activity.

PMID- 18056708
TI  - Macrophage migration inhibitory factor induces B cell survival by activation of a
      CD74-CD44 receptor complex.
AB  - Macrophage migration inhibitory factor (MIF) is an upstream activator of innate
      immunity that regulates subsequent adaptive responses. It was previously shown
      that in macrophages, MIF binds to a complex of CD74 and CD44, resulting in
      initiation of a signaling pathway. In the current study, we investigated the role
      of MIF in B cell survival. We show that in B lymphocytes, MIF initiates a
      signaling cascade that involves Syk and Akt, leading to NF-kappaB activation,
      proliferation, and survival in a CD74- and CD44-dependent manner. Thus, MIF
      regulates the adaptive immune response by maintaining the mature B cell
      population.

PMID- 18056709
TI  - Functional genomic characterization of mRNAs associated with TcPUF6, a pumilio
      like protein from Trypanosoma cruzi.
AB  - Trypanosoma cruzi is the protozoan parasite that causes Chagas disease or
      American trypanosomiasis. Kinetoplastid parasites could be considered as model
      organisms for studying factors involved in posttranscriptional regulation because
      they control gene expression almost exclusively at this level. The PUF
      (Pumilio/FBF1) protein family regulates mRNA stability and translation in
      eukaryotes, and several members have been identified in trypanosomatids. We used
      a ribonomic approach to identify the putative target mRNAs associated with
      TcPUF6, a member of the T. cruzi PUF family. TcPUF6 is expressed in discrete
      sites in the cytoplasm at various stages of the parasite life cycle and is not
      associated with the translation machinery. The overexpression of a tandem
      affinity purification-tagged TcPUF6 protein allowed the identification of
      associated mRNAs by affinity purification assays and microarray hybridization
      yielding nine putative target mRNAs. Whole expression analysis of transfected
      parasites showed that the mRNAs associated with TcPUF6 were down-regulated in
      populations overexpressing TcPUF6. The association of TcPUF6 with the TcDhh1
      helicase in vivo and the cellular co-localization of these proteins in
      epimastigote forms suggest that TcPUF6 promotes degradation of its associated
      mRNAs through interaction with RNA degradation complexes. Analysis of the mRNA
      levels of the putative TcPUF6-regulated genes during the parasite life cycle
      showed that their transcripts were up-regulated in metacyclic trypomastigotes. In
      these infective forms no co-localization between TcPUF6 and TcDhh1 was observed.
      Our results suggest that TcPUF6 regulates the half-lives of its associated
      transcripts via differential association with mRNA degradation complexes
      throughout its life cycle.

PMID- 18056711
TI  - Mutation of Gly721 alters DNA topoisomerase I active site architecture and
      sensitivity to camptothecin.
AB  - DNA topoisomerase I (Top1p) catalyzes the relaxation of supercoiled DNA via a
      concerted mechanism of DNA strand cleavage and religation. Top1p is the cellular
      target of the anti-cancer drug camptothecin (CPT), which reversibly stabilizes a
      covalent enzyme-DNA intermediate. Top1p clamps around duplex DNA, wherein the
      core and C-terminal domains are connected by extended alpha-helices (linker
      domain), which position the active site Tyr of the C-terminal domain within the
      catalytic pocket. The physical connection of the linker with the Top1p clamp as
      well as linker flexibility affect enzyme sensitivity to CPT. Crystallographic
      data reveal that a conserved Gly residue (located at the juncture between the
      linker and C-terminal domains) is at one end of a short alpha-helix, which
      extends to the active site Tyr covalently linked to the DNA. In the presence of
      drug, the linker is rigid and this alpha-helix extends to include Gly and the
      preceding Leu. We report that mutation of this conserved Gly in yeast Top1p
      alters enzyme sensitivity to CPT. Mutating Gly to Asp, Glu, Asn, Gln, Leu, or Ala
      enhanced enzyme CPT sensitivity, with the acidic residues inducing the greatest
      increase in drug sensitivity in vivo and in vitro. By contrast, Val or Phe
      substituents rendered the enzyme CPT-resistant. Mutation-induced alterations in
      enzyme architecture preceding the active site Tyr suggest these structural
      transitions modulate enzyme sensitivity to CPT, while enhancing the rate of DNA
      cleavage. We postulate that this conserved Gly residue provides a flexible hinge
      within the Top1p catalytic pocket to facilitate linker dynamics and the
      structural alterations that accompany drug binding of the covalent enzyme-DNA
      intermediate.

PMID- 18056710
TI  - Structure of the DNA repair helicase hel308 reveals DNA binding and
      autoinhibitory domains.
AB  - Hel308 is a superfamily 2 helicase conserved in eukaryotes and archaea. It is
      thought to function in the early stages of recombination following replication
      fork arrest and has a specificity for removal of the lagging strand in model
      replication forks. A homologous helicase constitutes the N-terminal domain of
      human DNA polymerase Q. The Drosophila homologue mus301 is implicated in double
      strand break repair and meiotic recombination. We have solved the high resolution
      crystal structure of Hel308 from the crenarchaeon Sulfolobus solfataricus,
      revealing a five-domain structure with a central pore lined with essential DNA
      binding residues. The fifth domain is shown to act as an autoinhibitory domain or
      molecular brake, clamping the single-stranded DNA extruded through the central
      pore of the helicase structure to limit the helicase activity of the enzyme. This
      provides an elegant mechanism to tune the processivity of the enzyme to its
      functional role. Hel308 can displace streptavidin from a biotinylated DNA
      molecule, and this activity is only partially inhibited when the DNA is pre-bound
      with abundant DNA-binding proteins RPA or Alba1, whereas pre-binding with the
      recombinase RadA has no effect on activity. These data suggest that one function
      of the enzyme may be in the removal of bound proteins at stalled replication
      forks and recombination intermediates.

PMID- 18056712
TI  - A critical role of cavin (polymerase I and transcript release factor) in caveolae
      formation and organization.
AB  - Cavin (PTRF) has been shown to be a highly abundant protein component of
      caveolae, but its functional role there is unknown. Here, we confirm that cavin
      co-localizes with caveolin-1 in adipocytes by confocal microscopy and co
      distributes with caveolin-1 in lipid raft fractions by sucrose gradient
      flotation. However, cavin does not directly associate with caveolin-1 as
      solubilization of caveolae disrupts their interaction. Cholesterol depletion with
      beta-cyclodextrin causes a significant down-regulation of cavin from plasma
      membrane lipid raft fractions. Overexpression of cavin in HEK293-Cav-1 cells and
      knockdown of cavin in 3T3-L1 adipocytes enhances and diminishes caveolin-1
      levels, respectively, indicating an important role for cavin in maintaining the
      level of caveolin-1. A truncated form of cavin, eGFP-cavin-1-322, which lacks 74
      amino acids from the C-terminal, reveals a microtubular network localization by
      confocal microscopy. Disruption of cytoskeletal elements with latrunculin B or
      nocodazole diminishes cavin expression without affecting the caveolin-1 amount.
      We propose that the presence of cavin on the inside surface of caveolae
      stabilizes these structures, probably through interaction with the cytoskeleton,
      and cavin therefore plays an important role in caveolae formation and
      organization.

PMID- 18056713
TI  - An investigation of the ligand binding properties and negative cooperativity of
      soluble insulin-like growth factor receptors.
AB  - To investigate the interaction of the insulin-like growth factor (IGF) ligands
      with the insulin-like growth factor type 1 receptor (IGF-1R), we have generated
      two soluble variants of the IGF-1R. We have recombinantly expressed the
      ectodomain of IGF-1R or fused this domain to the constant domain from the Fc
      fragment of mouse immunoglobulin. The ligand binding properties of these soluble
      IGF-1Rs for IGF-I and IGF-II were investigated using conventional ligand
      competition assays and BIAcore biosensor technology. In ligand competition
      assays, the soluble IGF-1Rs both bound IGF-I with similar affinities and a 5-fold
      lower affinity than that seen for the wild type receptor. In addition, both
      soluble receptors bound IGF-II with similar affinities to the wild type receptor.
      BIAcore analyses showed that both soluble IGF-1Rs exhibited similar ligand
      specific association and dissociation rates for IGF-I and for IGF-II. The soluble
      IGF-1R proteins both exhibited negative cooperativity for IGF-I, IGF-II, and the
      24-60 antibody, which binds to the IGF-1R cysteine-rich domain. We conclude that
      the addition of the self-associating Fc domain to the IGF-1R ectodomain does not
      affect ligand binding affinity, which is in contrast to the soluble ectodomain of
      the IR. This study highlights some significant differences in ligand binding
      modes between the IGF-1R and the insulin receptor, which may ultimately
      contribute to the different biological activities conferred by the two receptors.

PMID- 18056714
TI  - Structure and function of sedoheptulose-7-phosphate isomerase, a critical enzyme
      for lipopolysaccharide biosynthesis and a target for antibiotic adjuvants.
AB  - The barrier imposed by lipopolysaccharide (LPS) in the outer membrane of Gram
      negative bacteria presents a significant challenge in treatment of these
      organisms with otherwise effective hydrophobic antibiotics. The absence of L
      glycero-D-manno-heptose in the LPS molecule is associated with a dramatically
      increased bacterial susceptibility to hydrophobic antibiotics and thus enzymes in
      the ADP-heptose biosynthesis pathway are of significant interest. GmhA catalyzes
      the isomerization of D-sedoheptulose 7-phosphate into D-glycero-D-manno-heptose 7
      phosphate, the first committed step in the formation of ADP-heptose. Here we
      report structures of GmhA from Escherichia coli and Pseudomonas aeruginosa in
      apo, substrate, and product-bound forms, which together suggest that GmhA adopts
      two distinct conformations during isomerization through reorganization of
      quaternary structure. Biochemical characterization of GmhA mutants, combined with
      in vivo analysis of LPS biosynthesis and novobiocin susceptibility, identifies
      key catalytic residues. We postulate GmhA acts through an enediol-intermediate
      isomerase mechanism.

PMID- 18056715
TI  - Nitrite reductase activity of hemoglobin S (sickle) provides insight into
      contributions of heme redox potential versus ligand affinity.
AB  - Hemoglobin A (HbA) is an allosterically regulated nitrite reductase that reduces
      nitrite to NO under physiological hypoxia. The efficiency of this reaction is
      modulated by two intrinsic and opposing properties: availability of unliganded
      ferrous hemes and R-state character of the hemoglobin tetramer. Nitrite is
      reduced by deoxygenated ferrous hemes, such that heme deoxygenation increases the
      rate of NO generation. However, heme reactivity with nitrite, represented by its
      bimolecular rate constant, is greatest when the tetramer is in the R quaternary
      state. The mechanism underlying the higher reactivity of R-state hemes remains
      elusive. It can be due to the lower heme redox potential of R-state ferrous hemes
      or could reflect the high ligand affinity geometry of R-state tetramers that
      facilitates nitrite binding. We evaluated the nitrite reductase activity of
      unpolymerized sickle hemoglobin (HbS), whose oxygen affinity and cooperativity
      profile are equal to those of HbA, but whose heme iron has a lower redox
      potential. We now report that HbS exhibits allosteric nitrite reductase activity
      with competing proton and redox Bohr effects. In addition, we found that solution
      phase HbS reduces nitrite to NO significantly faster than HbA, supporting the
      thesis that heme electronics (i.e. redox potential) contributes to the high
      reactivity of R-state deoxy-hemes with nitrite. From a pathophysiological
      standpoint, under conditions where HbS polymers form, the rate of nitrite
      reduction is reduced compared with HbA and solution-phase HbS, indicating that
      HbS polymers reduce nitrite more slowly.

PMID- 18056716
TI  - BMP-2 induces Osterix expression through up-regulation of Dlx5 and its
      phosphorylation by p38.
AB  - Osterix, a zinc-finger transcription factor, is specifically expressed in
      osteoblasts and osteocytes of all developing bones. Because no bone formation
      occurs in Osterix null mice, Osterix is thought to be an essential regulator of
      osteoblast differentiation. We report that bone morphogenetic protein-2 (BMP-2)
      induces an increase in Osterix expression, which is mediated through a
      homeodomain sequence located in the proximal region of the Osterix promoter. Our
      results demonstrate that induction of Dlx5 by BMP-2 mediates Osterix
      transcriptional activation. First, BMP-2 induction of Dlx5 precedes the induction
      of Osterix. Second, Dlx5 binds to the BMP-responsive homeodomain sequences both
      in vitro and in vivo. Third, Dlx5 overexpression and knock-down assays
      demonstrate its role in activating Osterix expression in response to BMP-2.
      Furthermore, we show that Dlx5 is a novel substrate for p38 MAPK in vitro and in
      vivo and that Ser-34 and Ser-217 are the sites phosphorylated by p38.
      Phosphorylation at Ser-34/217 increases the transactivation potential of Dlx5.
      Thus, we propose that BMP activates expression of Osterix through the induction
      of Dlx5 and its further transcriptional activation by p38-mediated
      phosphorylation.

PMID- 18056717
TI  - Defining the proton entry point in the bacterial respiratory nitric-oxide
      reductase.
AB  - The bacterial respiratory nitric-oxide reductase (NOR) is a member of the
      superfamily of O(2)-reducing, proton-pumping, heme-copper oxidases. Even although
      nitric oxide reduction is a highly exergonic reaction, NOR is not a proton pump
      and rather than taking up protons from the cytoplasmic (membrane potential
      negative) side of the membrane, like the heme-copper oxidases, NOR derives its
      substrate protons from the periplasmic (membrane potential-positive) side of the
      membrane. The molecular details of this non-electrogenic proton transfer are not
      yet resolved, so in this study we have explored a role in a proposed proton
      pathway for a conserved surface glutamate (Glu-122) in the catalytic subunit
      (NorB). The effect of substituting Glu-122 with Ala, Gln, or Asp on a single
      turnover of the reduced NOR variants with O(2), an alternative and experimentally
      tractable substrate for NOR, was determined. Electron transfer coupled to proton
      uptake to the bound O(2) is severely and specifically inhibited in both the E122A
      and E122Q variants, establishing the importance of a protonatable side chain at
      this position. In the E122D mutant, proton uptake is retained but it is
      associated with a significant increase in the observed pK(a) of the group
      donating protons to the active site. This suggests that Glu-122 is important in
      defining this proton donor. A second nearby glutamate (Glu-125) is also required
      for the electron transfer coupled to proton uptake, further emphasizing the
      importance of this region of NorB in proton transfer. Because Glu-122 is
      predicted to lie near the periplasmic surface of NOR, the results provide strong
      experimental evidence that this residue contributes to defining the aperture of a
      non-electrogenic "E-pathway" that serves to deliver protons from the periplasm to
      the buried active site in NOR.

PMID- 18056718
TI  - Analysis of serum FSH bioactivity in a patient with an FSH-secreting pituitary
      microadenoma and multicystic ovaries: A case report.
AB  - FSH-secreting pituitary adenoma (FSHoma) is often associated with increased
      levels of serum FSH and ovarian hyperstimulation syndrome (OHSS). The OHSS has
      historically been attributed to elevated FSH production by the FSHoma; however,
      some FSHoma patients with OHSS have normal serum FSH levels. OHSS may result not
      from increased FSH levels, but also from increased bioactivity of the FSH derived
      from the adenoma. To address this, we measured the FSH bioactivity in the serum
      of a 40-year-old woman with an FSHoma and OHSS, whose FSH levels were normal.
      Chinese hamster ovary cells stably expressing FSH receptors were prepared and
      transfected with a cAMP-responsive element-driven luciferase reporter plasmid.
      Cells were then treated with recombinant human FSH (rhFSH), the patient's sera,
      or sera from controls, collected at different time points, and subjected to a
      luciferase assay. Luciferase activity was increased in response to rhFSH in a
      dose-dependent manner. The responsiveness was further augmented by co-addition of
      a 3-methyl isobutylxanthine, which improved the sensitivity of our assay.
      Unexpectedly, the serum FSH bioactivity/immunoactivity ratio of the patient was
      mostly equal to that of normal subjects. This was confirmed with a granulosa cell
      aromatase assay. This case report suggests that alternate explanations may exist
      for the OHSS phenotype seen in some FSHoma patients.

PMID- 18056719
TI  - Urinary hMG versus recombinant FSH for controlled ovarian hyperstimulation
      following an agonist long down-regulation protocol in IVF or ICSI treatment: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Since the most recent Cochrane review on hMG versus rFSH for
      controlled ovarian hyperstimulation following a long down-regulation protocol,
      several new trials have emerged. METHODS: We conducted a systematic review and
      meta-analysis of randomized trials comparing the effectiveness of hMG versus rFSH
      following a long down-regulation protocol in IVF-ICSI cycles, on the primary
      outcome of live birth per woman randomized, as well as several other secondary
      outcomes. Searches were conducted in MEDLINE, EMBASE, Science Direct, Cochrane
      Library and databases of abstracts (last search January 2007). RESULTS: Seven
      randomized trials, consisting of a total of 2159 randomized women, were
      identified. A meta-analysis of these trials showed a significant increase in live
      birth rate with hMG when compared with rFSH (relative risk, RR = 1.18, 95% CI:
      1.02-1.38, P = 0.03). The heterogeneity test was non-significant (P = 0.97),
      suggesting that there was no statistical inconsistency between the seven studies.
      The pooled risk difference (RD) for the outcome of live birth rate was 4% (95%
      CI: 1-7%) for these study populations. There was an increase in clinical
      pregnancy rates with hMG when compared with rFSH (RR = 1.17, 95% CI 1.03-1.34).
      No significant differences were noted for gonadotrophin use, spontaneous
      abortion, multiple pregnancy, cancellation and ovarian hyperstimulation syndrome
      rates. CONCLUSIONS: For the populations in the randomized trials, hMG was
      associated with a pooled 4% increase in live birth rate when compared with rFSH
      in IVF-ICSI treatment following a long down-regulation protocol.

PMID- 18056722
TI  - Translational genomics for bioenergy production: there's room for more than one
      model.

PMID- 18056724
TI  - Using qualitative methodology to inform an Indigenous-owned oral health promotion
      initiative in Australia.
AB  - Indigenous Australians experience poor oral health. Oral health perceptions among
      a group of rural-dwelling Indigenous Australians were explored so that a
      culturally appropriate, community-owned oral health promotion initiative might be
      developed. Focus group methodology was used, with prompt questions including oral
      health knowledge, oral health's role in general health, how community oral health
      had changed in recent times, the causes of poor oral health and ways to prevent
      poor oral health at a community level. Some 34 participants took part; age range
      21-72 years. A core category emerged from the data and was labelled 'cultural
      adaptation'. Five sub-categories were also identified; 'lifestyle changes', 'oral
      health behaviours', 'barriers to dental care', 'impact of poor oral health' and
      'oral health literacy'. Participants felt that historical legacy impacted on the
      oral health of community members, through continued practices of being told what
      to do, where to live and what oral health services were available to them.
      Participants perceived they had little power over their oral health or oral
      health care decisions. Findings from the focus group discussions were used in the
      development of a context-specific, oral health promotion initiative, which
      involved construction of an audiovisual tool in Phase I and a series of
      interactive, context-specific seminars focused on key issues raised in the focus
      groups in Phase II. Oral health promotion initiatives among rural-dwelling
      Indigenous Australians may be more successful if perceptions of the anticipated
      audience are considered in the design stage of such strategies.

PMID- 18056725
TI  - The role of vitamin D3 in preventing infections.

PMID- 18056726
TI  - Tongue necrosis: a rare presentation of temporal arteritis.

PMID- 18056727
TI  - Determinants of outcome and safety of intravenous rt-PA therapy in the very old:
      a clinical registry study and systematic review.

PMID- 18056729
TI  - Treating dementia: will the NICE guidance 2006 change our clinical practice?

PMID- 18056728
TI  - Lives of the artists: differences in longevity between old master sculptors and
      painters.

PMID- 18056730
TI  - Whither geriatrics? Do we need another Marjory Warren?

PMID- 18056731
TI  - Rethinking individual and community fall prevention strategies: a meta-regression
      comparing single and multifactorial interventions.
AB  - BACKGROUND: Guidelines recommend that fall prevention programmes for older people
      include multifactorial interventions. OBJECTIVE: We aimed to determine if
      randomised controlled trial evidence supports interventions with multiple
      components over single strategies in community based fall prevention. METHODS: We
      searched the literature for trials of interventions aimed at preventing falls. We
      included trials if they met the following criteria: (i) participants were
      randomly allocated to intervention and control groups, (ii) all participants were
      aged 65 years or older, (iii) the majority lived independently in the community,
      (iv) fall events were recorded prospectively using a diary or calendar during the
      entire trial and monitored at least monthly, (v) follow up was for 12 months or
      longer, (vi) at least 70% of participants completed the trial, (vii) all falls
      during the trial for at least 50 participants were included in the analysis, and
      (viii) a relative rate ratio with 95% CI comparing the number of falls in the
      intervention and control groups was reported. We calculated a pooled rate ratio
      separately for trials testing multifactorial and single interventions and
      compared their overall efficacy using meta-regression. RESULTS: Meta-regression
      showed that single interventions were as effective in reducing falls as
      interventions with multiple components (pooled rate ratios 0.77, 95% CI 0.67-0.89
      and 0.78, 0.68-0.89 respectively). CONCLUSION: Multifactorial fall prevention
      interventions are effective for individual patients. However, for community
      programmes for populations at risk, targeted single interventions are as
      effective as multifactorial interventions, may be more acceptable and cost
      effective.

PMID- 18056732
TI  - Palliative care ward for the elderly.

PMID- 18056733
TI  - Mortality and morbidity attributable to inadequate empirical antimicrobial
      therapy in patients admitted to the ICU with sepsis: a matched cohort study.
AB  - OBJECTIVES: To determine the attributable mortality and excess length of stay
      (LOS) associated with the use of inadequate empirical antimicrobial therapy in
      patients with sepsis at admission to the intensive care unit (ICU). METHODS: A
      retrospective matched cohort study was performed using a prospectively collected
      database at a 40 bed general ICU at a university public hospital. Patients who
      received inadequate antimicrobial therapy at admission to the ICU (exposed) were
      matched with controls (unexposed) on the basis of origin of sepsis, inflammatory
      response at admission, surgical or medical status, hospital- or community
      acquired sepsis, APACHE II score (+/-2 points) and age (+/-10 years). Clinical
      outcome was assessed by in-hospital mortality, and this analysis was also
      performed in those pairs without nosocomial infection in the ICU. RESULTS: Eighty
      seven pairs were successfully matched. Fifty-nine exposed patients died [67.8%
      mortality (95% CI, 58.0-77.6%)] and 25 unexposed controls died [28.7% mortality
      (95% CI, 19.2-38.2%)] (P < 0.001). Excess in-hospital mortality was estimated to
      be 39.1%. The rate of nosocomial infection was significantly higher in patients
      with inadequate empirical therapy (16.1%) than in those treated empirically with
      adequate antibiotics (3.4%) (P = 0.013). Excess in-hospital mortality was 31.4%
      after excluding those 17 pairs that developed a nosocomial infection in the ICU.
      Inadequate antimicrobial therapy was associated with a significant increment in
      duration of hospitalization (15 days in surviving pairs). CONCLUSIONS: Inadequate
      antimicrobial therapy at admission to the ICU with sepsis is associated with
      excess mortality and increases LOS.

PMID- 18056735
TI  - Can prolonged exercise-induced myocardial ischaemia be innocuous?

PMID- 18056736
TI  - Rfold: an exact algorithm for computing local base pairing probabilities.
AB  - MOTIVATION: Base pairing probability matrices have been frequently used for the
      analyses of structural RNA sequences. Recently, there has been a growing need for
      computing these probabilities for long DNA sequences by constraining the maximal
      span of base pairs to a limited value. However, none of the existing programs can
      exactly compute the base pairing probabilities associated with the energy model
      of secondary structures under such a constraint. RESULTS: We present an algorithm
      that exactly computes the base pairing probabilities associated with the energy
      model under the constraint on the maximal span W of base pairs. The complexity of
      our algorithm is given by O(NW2) in time and O(N+W2) in memory, where N is the
      sequence length. We show that our algorithm has a higher sensitivity to the true
      base pairs as compared to that of RNAplfold. We also present an algorithm that
      predicts a mutually consistent set of local secondary structures by maximizing
      the expected accuracy function. The comparison of the local secondary structure
      predictions with those of RNALfold indicates that our algorithm is more accurate.
      Our algorithms are implemented in the software named 'Rfold.' AVAILABILITY: The
      C++ source code of the Rfold software and the test dataset used in this study are
      available at http://www.ncrna.org/software/Rfold/.

PMID- 18056737
TI  - Normal-appearing white matter in multiple sclerosis is in a subtle balance
      between inflammation and neuroprotection.
AB  - Multiple sclerosis is a chronic inflammatory disease of the CNS. Although
      progressive axonal injury and diffuse inflammatory damage has been shown in the
      chronic phase of the disease, little is known about the molecular mechanisms
      underlying these pathological processes. In order to identify these mechanisms,
      we have studied the gene expression profile in non-lesion containing tissue, the
      so-called normal-appearing white matter (NAWM). We performed differential gene
      expression analysis and quantitative RT-PCR on subcortical white matter from 11
      multiple sclerosis and 8 control cases. Differentially expressed genes were
      further analysed in detail by in situ hybridization and immunofluorescence
      studies. We show that genes known to be involved in anti-inflammatory and
      protective mechanisms such as STAT6, JAK1, IL-4R, IL-10, Chromogranin C and Hif
      1alpha are consistently upregulated in the multiple sclerosis NAWM. On the other
      hand, genes involved in pro-inflammatory mechanisms, such as STAT4, IL-1beta and
      MCSF, were also upregulated but less regularly. Immunofluorescence colocalization
      analysis revealed expression of STAT6, JAK1, IL-4R and IL-13R mainly in
      oligodendrocytes, whereas STAT4 expression was detected predominantly in
      microglia. In line with these data, in situ hybridization analysis showed an
      increased expression in multiple sclerosis NAWM of HIF-1alpha in oligodendrocytes
      and HLA-DRalpha in microglia cells. The consistency of the expression levels of
      STAT6, JAK1, JAK3 and IL-4R between the multiple sclerosis cases suggests an
      overall activation of the STAT6-signalling pathway in oligodendrocytes, whereas
      the expression of STAT4 and HLA-DRalpha indicates the activation of pro
      inflammatory pathways in microglia. The upregulation of genes involved in anti
      inflammatory mechanisms driven by oligodendrocytes may protect the CNS
      environment and thus limit lesion formation, whereas the activation of pro
      inflammatory mechanisms in microglia may favour disease progression. Altogether,
      our data suggests an endogenous inflammatory reaction throughout the whole white
      matter of multiple sclerosis brain, in which oligodendrocytes actively
      participate. This reaction might further influence and to some extent facilitate
      lesion formation.

PMID- 18056738
TI  - CAG repeat size correlates to electrophysiological motor and sensory phenotypes
      in SBMA.
AB  - Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, lower motor neuron
      disease caused by an aberrant elongation of a CAG repeat in the androgen receptor
      (AR) gene. The main symptoms are weakness and atrophy of bulbar, facial and limb
      muscles, but sensory disturbances are frequently found in SBMA patients. Motor
      symptoms have been attributed to the accumulation of mutant AR in the nucleus of
      lower motor neurons, which is more profound in patients with a longer CAG repeat.
      We examined nerve conduction properties including F-waves in a total of 106
      patients with genetically confirmed SBMA (mean age at data collection = 53.8
      years; range = 31-75 years) and 85 control subjects. Motor conduction velocities
      (MCV), compound muscle action potentials (CMAP), sensory conduction velocities
      (SCV) and sensory nerve action potentials (SNAP) were significantly decreased in
      all nerves examined in the SBMA patients compared with that in the normal
      controls, indicating that axonal degeneration is the primary process in both
      motor and sensory nerves. More profound abnormalities were observed in the nerves
      of the upper limbs than in those of the lower limbs. F-waves in the median nerve
      were absent in 30 of 106 cases (28.3%), but no cases of absent F-waves were
      observed in the tibial nerve. From an analysis of the relationship between CMAPs
      and SNAPs, patients were identified with different electrophysiological
      phenotypes: motor-dominant, sensory-dominant and non-dominant phenotypes. The CAG
      repeat size and the age at onset were significantly different among the patients
      with motor- and sensory-dominant phenotypes, indicating that a longer CAG repeat
      is more closely linked to the motor-dominant phenotype and a shorter CAG repeat
      is more closely linked to the sensory-dominant phenotype. Furthermore, when we
      classified the patients by CAG repeat size, CMAP values showed a tendency to be
      decreased in patients with a longer CAG repeat (> or =47), while SNAPs were
      significantly decreased in patients with a shorter CAG repeat (<47). In addition,
      we found that the frequency of aggregation in the sensory neuron cytoplasm tended
      to inversely correlate with the CAG repeat size in the autopsy study, supporting
      the view that the CAG repeat size differentially correlates with motor- and
      sensory-dominant phenotypes. In conclusion, our results suggest that there are
      unequivocal electrophysiological phenotypes influenced by CAG repeat size in
      SBMA.

PMID- 18056739
TI  - An investigation of the retinal nerve fibre layer in progressive multiple
      sclerosis using optical coherence tomography.
AB  - Axonal loss is thought to be the predominant cause of disability in progressive
      multiple sclerosis (MS). The retinal nerve fibre layer (RNFL) is composed largely
      of unmyelinated axons of retinal ganglion cells, and is accessible to study with
      optical coherence tomography (OCT), giving a measure of axonal loss. OCT measures
      of the RNFL thickness (RNFLT) and macular volume were studied in 23 patients with
      primary progressive multiple sclerosis (primary progressive MS) (13 male; 10
      female; mean age 52 years; median EDSS 6.0; mean disease duration 11 years), and
      27 patients with secondary progressive multiple sclerosis (secondary progressive
      MS) (8 male; 19 female; mean age 50 years; median EDSS 6; mean disease duration
      22 years). Of the patients with secondary progressive MS, 14 had clinical history
      of optic neuritis (ON) in a single eye; the remaining patients had not had ON.
      Twenty healthy controls (11 male; 9 female; mean age 46 years) had RNFLT and
      macular volume studied. Of the patients' eyes not previously affected by ON, both
      the mean RNFL thickness and macular volume were reduced when compared with
      control values. The mean RNFL thickness and macular volume were significantly
      reduced in secondary progressive MS, but not in primary progressive MS when
      compared with control RNFL thickness and macular volume. RNFL loss was most
      evident in the temporal quadrant, where significant reduction was seen in primary
      progressive MS versus controls and in secondary versus primary progressive MS.
      There were significant correlations of decreased RNFLT and macular volume with
      measures of visual acuity, low contrast visual acuity and visual field mean
      deviation in the MS patients. There are significant global reductions in RNFLT
      and macular volume in the eyes of secondary progressive MS patients not
      previously affected by ON, but not in primary progressive MS patients, compared
      with controls. This may indicate a difference in the extent of the pathological
      processes that cause axonal loss in the retina, and by inference the optic nerve,
      in secondary progressive MS and primary progressive MS.

PMID- 18056740
TI  - Hemiarthroplasty or internal fixation for intracapsular displaced femoral neck
      fractures: randomised controlled trial.
AB  - OBJECTIVE: To compare the functional results after displaced fractures of the
      femoral neck treated with internal fixation or hemiarthroplasty. DESIGN:
      Randomised trial with blinding of assessments of functional results. SETTING:
      University hospital. PARTICIPANTS: 222 patients; 165 (74%) women, mean age 83
      years. Inclusion criteria were age above 60, ability to walk before the fracture,
      and no major hip pathology, regardless of cognitive function. INTERVENTIONS:
      Closed reduction and two parallel screws (112 patients) and bipolar cemented
      hemiarthroplasty (110 patients). Follow-up at 4, 12, and 24 months. MAIN OUTCOME
      MEASURES: Hip function (Harris hip score), health related quality of life (Eq
      5d), activities of daily living (Barthel index). In all cases high scores
      indicate better function. RESULTS: Mean Harris hip score in the hemiarthroplasty
      group was 8.2 points higher (95% confidence interval 2.8 to 13.5 points, P=0.003)
      at four months and 6.7 points (1.5 to 11.9 points, P=0.01) higher at 12 months.
      Mean Eq-5d index score at 24 months was 0.13 higher in the hemiarthroplasty group
      (0.01 to 0.25, P=0.03). The Eq-5d visual analogue scale was 8.7 points higher in
      the hemiarthroplasty group after 4 months (1.9 to 15.6, P=0.01). After 12 and 24
      months the percentage scoring 95 or 100 on the Barthel index was higher in the
      hemiarthroplasty group (relative risk 0.67, 0.47 to 0.95, P=0.02. and 0.63, 0.42
      to 0.94, P=0.02, respectively). Complications occurred in 56 (50%) patients in
      the internal fixation group and 16 (15%) in the hemiarthroplasty group (3.44,
      2.11 to 5.60, P<0.001). In each group 39 patients (35%) died within 24 months
      (0.98, 0.69 to 1.40, P=0.92) CONCLUSIONS: Hemiarthroplasty is associated with
      better functional outcome than internal fixation in treatment of displaced
      fractures of the femoral neck in elderly patients. TRIAL REGISTRATION:
      NCT00464230.

PMID- 18056741
TI  - Osteoarthritis of the knee in primary care.

PMID- 18056742
TI  - Influences on older people's decision making regarding choice of topical or oral
      NSAIDs for knee pain: qualitative study.
AB  - OBJECTIVE: To explore the factors that influence older people's decision making
      regarding use of topical or oral ibuprofen for their knee pain. DESIGN:
      Qualitative interview study nested within a randomised controlled trial and a
      patient preference study that compared advice to use oral or topical non
      steroidal anti-inflammatory drugs (NSAIDs) for knee pain in older people.
      SETTING: 11 general practices. PARTICIPANTS: 30 people aged > or =50 with knee
      pain. RESULTS: Participants' decision making was influenced by their perceptions
      of the associated risk of adverse effects, presence of other illness, nature of
      their pain, advice received, and practicality. Although participants'
      understanding of how the medications worked was sometimes poor their decision
      making about the use of NSAIDs seemed logical and appropriate. Participants'
      model for treatment was to use topical NSAIDs for mild, local, and transient pain
      and oral NSAIDs for moderate to severe, generalised, and constant pain (in the
      absence of other more serious illness or risk of adverse effects). Participants
      showed marked tolerance and normalisation of adverse effects. CONCLUSION:
      Participants had clear ideas about the appropriate use of oral and topical
      NSAIDs. Taking such views into account when prescribing may improve adherence,
      judgment of efficacy, and the doctor-patient relationship. Tolerance and
      normalisation of adverse effects in these patients indicate that closer
      monitoring of older people who use NSAIDs might be needed.

PMID- 18056744
TI  - Treatment of displaced intracapsular hip fractures in elderly patients.

PMID- 18056743
TI  - Advice to use topical or oral ibuprofen for chronic knee pain in older people:
      randomised controlled trial and patient preference study.
AB  - OBJECTIVE: To determine whether older patients with chronic knee pain should be
      advised to use topical or oral non-steroidal anti-inflammatory drugs (NSAIDs).
      DESIGN: Randomised controlled trial and patient preference study. SETTING: 26
      general practices. PARTICIPANTS: People aged > or =50 with knee pain: 282 in
      randomised trial and 303 in preference study. INTERVENTIONS: Advice to use
      topical or oral ibuprofen. Primary outcome measures WOMAC (Western Ontario and
      McMaster Universities) osteoarthritis index, major and minor adverse effects.
      RESULTS: Changes in global WOMAC scores at 12 months were equivalent. In the
      randomised trial the difference (topical minus oral) was two points (95%
      confidence interval -2 to 6); in the preference study, it was one point (-4 to
      6). There were no differences in major adverse effects in the trial or study. The
      only significant differences in secondary outcomes were in the randomised trial.
      The oral group had more respiratory adverse effects (17% v 7%,95% confidence
      interval for difference -17% to -2%), the change in serum creatinine was 3.7
      mmol/l less favourable (0.9 micromol/l to 6.5 micromol/l); and more participants
      changed treatments because of adverse effects (16% v 1%, -16% to -5%). In the
      topical group more participants had chronic pain grade III or IV at three months,
      and more participants changed treatment because of ineffectiveness. CONCLUSIONS:
      Advice to use oral or topical preparations has an equivalent effect on knee pain
      over one year, and there are more minor side effects with oral NSAIDs. Topical
      NSAIDs may be a useful alternative to oral NSAIDs. TRIAL REGISTRATION: ISRCTN
      79353052.

PMID- 18056745
TI  - Apoptosis of cultured astrocytes induced by the copper and neocuproine complex
      through oxidative stress and JNK activation.
AB  - Astrocytes play a critical neurotrophic and neuroprotective role in the brain,
      and improper function of these cells may contribute to the onset of
      neurodegenerative diseases. Because astrocytes are known to be enriched with Cu
      chaperone proteins, it is important to understand the factors that may lead to
      cytotoxic effects of Cu on astrocytes. In this report, we demonstrated a dramatic
      potentiating effect of neocuproine (NCP), a membrane permeable metal chelator, on
      Cu, but not Fe or Pb, in inducing apoptosis of cultured astrocytes. It was
      estimated that individually, CuCl2 and NCP only weakly exhibited cytotoxic
      effects on astrocytes, with EC50 of 180 and 600 microM, respectively. However,
      NCP at a nontoxic concentration of 10 microM markedly reduced EC50 of Cu to 0.35
      microM (physiological concentration) and Cu (10 microM) reduced EC50 of NCP down
      to 0.06 microM. The mechanisms underlying these dramatic potentiation effects are
      elucidated. NCP increased the intracellular concentration of Cu in astrocytes and
      a nonpermeable Cu chelator, bathocuproine disulfonate was able to abolish all of
      the apoptotic signaling. Cell death was determined to be via apoptosis due to
      increased reactive oxygen species production, mitochondrial dysfunction,
      depletion of glutathione and adenosine triphosphate, cytochrome c release, c-Jun
      N-terminal kinase, and caspase-3 activation, and poly-ADP-ribose polymerase
      degradation. This finding, coupled with our previous reports, suggests that metal
      chelators (NCP, dithiocarbamate and disulfiram) should be cautiously used as they
      may potentiate a cytotoxic effect of endogenous Cu on astrocytes. Their clinical
      implications in the etiology of neurodegenerative diseases deserve further
      investigation.

PMID- 18056746
TI  - Leading the way: a conversation with HHS secretary Mike Leavitt. Interview by
      Leonard D. Schaeffer.
AB  - In January 2005, Michael O. Leavitt was sworn in as the twentieth secretary of
      health and human services (HHS). The former three-term governor of Utah reveals
      how his management of HHS reflects his experiences managing private- and public
      sector organizations. The discussion explores his perspective that using health
      information technology (IT) to modernize health care and create value must be
      done through collaboration, not government mandate. Secretary Leavitt says that
      new approaches based on linking reimbursement with results must be adopted
      incrementally, as more is learned about carrying out such approaches. But he also
      says that it is time to begin linking reimbursement with health IT adoption.

PMID- 18056747
TI  - How common is repetitive strain injury?
AB  - OBJECTIVE: Statistics from Labour Force Surveys are widely quoted as evidence for
      the scale of occupational illness in Europe. However, occupational attribution
      depends on whether participants believe their health problem is caused or
      aggravated by work, and personal beliefs may be unreliable. The authors assessed
      the potential for error for work-associated arm pain. METHODS: A questionnaire
      was mailed [corrected] to working-aged adults, randomly chosen from five British
      general practices. They were asked about: occupational activities; mental health;
      self-rated health; arm pain; and beliefs about its causation. Those in work (n =
      1769) were asked about activities likely to cause arm pain, from which the
      authors derived a variable for exposure to any "arm-straining" occupational
      activity. The authors estimated the relative risk (RR) from arm-straining
      activity, using a modified Cox model, and derived the population attributable
      fraction (PAF). They compared the proportion of arm pain cases reporting their
      symptom as caused or made worse by work with the calculated PAF, overall and for
      subsets defined by demographic and other characteristics. RESULTS: Arm pain in
      the past year was more common in the 1143 subjects who reported exposure to arm
      straining occupational activity (RR 1.2, 95% CI 1.1 to 1.5). In the study sample
      as a whole, 53.9% of 817 cases reported their arm pain as work-associated,
      whereas the PAF for arm-straining occupational activity was only 13.9%. The ratio
      of cases reported as work-related to the calculated attributable number was
      substantially higher below 50 years (5.4) than at older ages (3.0) and higher in
      those with worse self-rated and mental health. CONCLUSIONS: Counting people with
      arm pain which they believe to be work-related can overestimate the number of
      cases attributable to work substantially. This casts doubt on the validity of a
      major source of information used by European governments to evaluate their
      occupational health strategies.

PMID- 18056748
TI  - Effort-reward imbalance and incidence of low back and neck injuries in San
      Francisco transit operators.
AB  - OBJECTIVES: Effort-reward imbalance (ERI) has been associated with
      musculoskeletal disorders in cross-sectional and case-control studies, but no
      longitudinal studies have been published yet. The effect of ERI on the incidence
      of compensated low back and neck injuries was examined in a 7.5-year follow-up
      study among 1179 San Francisco transit operators. METHODS: Data from medical
      examination and a survey on working conditions and health were linked to
      administrative workers' compensation databases. HRs for first low back and first
      neck injury were calculated with multivariate Cox regression models. Additional
      analyses accounted for severity of injury based on medical diagnosis. RESULTS: A
      1 SD increase in ERI was associated with compensated low back (HR 1.13, 95% CI
      1.02 to 1.26) and neck injuries (HR 1.14, 95% CI 1.02 to 1.27) after adjusting
      for gender, age, height, weight, years of professional driving, weekly driving
      hours, vehicle type, ergonomic problems, pain at baseline and job strain. The
      highest quartile of ERI showed an HR of 1.32 (95% CI 0.94 to 1.86) for low back
      injuries and an HR of 1.66 (95% CI 1.16 to 2.38) for neck injuries after
      adjustment for all covariates. The associations between ERI and low back injury
      were stronger for more severe injuries (HR 1.23, 95% CI 1.03 to 1.46 for a 1 SD
      increase in ERI) than for less severe injuries (HR 1.11, 95% CI 0.96 to 1.28).
      For neck injuries, stronger relationships were found for less severe injuries (HR
      1.15, 95% CI 1.02 to 1.29) than for more severe injuries (HR 1.10, 95% CI 0.86 to
      1.41). CONCLUSIONS: ERI is associated with low back and neck injuries in San
      Francisco transit operators independently of individual worker characteristics,
      physical workload, ergonomic problems, baseline pain and job strain. Effect sizes
      differ by injury severity.

PMID- 18056749
TI  - Short-term associations between fine and coarse particles and hospital admissions
      for cardiorespiratory diseases in six French cities.
AB  - OBJECTIVES: Little is known about the potential health effects of the coarse
      fraction of ambient particles. The aim of this study is to estimate the links
      between fine (PM(2.5)) and coarse particle (PM(2.5-10)) levels and
      cardiorespiratory hospitalisations in six French cities during 2000-2003.
      METHODS: Data on the daily numbers of hospitalisations for respiratory,
      cardiovascular, cardiac and ischaemic heart diseases were collected. Associations
      between exposure indicators and hospitalisations were estimated in each city
      using a Poisson regression model, controlling for confounding factors (seasons,
      days of the week, holidays, influenza epidemics, pollen counts, temperature) and
      temporal trends. City-specific findings were combined to obtain excess relative
      risks (ERRs) associated with a 10 mug/m(3) increase in PM(2.5) and PM(2.5-10
      )levels. RESULTS: We found positive associations between indicators of
      particulate pollution and hospitalisations for respiratory infection, with an ERR
      of 4.4% (95% CI 0.9 to 8.0) for PM(2.5-10 )and 2.5% (95% CI 0.1 to 4.8) for
      PM(2.5). Concerning respiratory diseases, no association was observed with
      PM(2.5), whereas positive trends were found with PM(2.5-10), with a significant
      association for the 0-14-year-old age group (ERR 6.2%, 95% CI 0.4 to 12.3).
      Concerning cardiovascular diseases, positive associations were observed between
      PM(2.5) levels and each indicator, although some did not reach significance;
      trends with PM(2.5-10 )were weaker and non-significant except for ischaemic heart
      disease in the elderly (ERR 6.4%, 95% CI 1.6 to 11.4). CONCLUSIONS: In accordance
      with other studies, our results indicate that the coarse fraction may have a
      stronger effect than the fine fraction on some morbidity endpoints, especially
      respiratory diseases.

PMID- 18056750
TI  - In vitro bioassays for androgens and their diagnostic applications.
AB  - Androgen levels are measured in today's clinical practice almost exclusively by
      immunoassays. The androgen that is most frequently determined is testosterone
      (T), but sometimes also the levels of other testicular, ovarian and adrenal
      androgens such as 5alpha-dihydrotestosterone, androstenedione,
      dehydroepiandrosterone and its sulphate may be determined. In many instances,
      especially when androgen levels are low (as in women and children), the quality
      of the immunomeasurements is insufficient and the correlation between hormone
      levels and clinical symptoms is poor. One alternative to improve the clinical
      relevance of androgen measurements is provided by the recently developed in vitro
      bioassays of total androgen bioactivity in serum. These assays are not yet ready
      for routine laboratory diagnostics, but they provide a useful tool for clinical
      research in disturbances of androgen production. Another application of these
      assays is the screening for androgenic and antiandrogenic activity in chemical
      compounds, environmental samples and when suspecting androgen abuse. The purpose
      of this article is to introduce the current problems of androgen measurement by
      immunoassays, to describe the novel in vitro bioassay techniques and to review
      the current information on their application in clinical research.

PMID- 18056751
TI  - Wernicke's encephalopathy revisited. Translation of the case history section of
      the original manuscript by Carl Wernicke 'Lehrbuch der Gehirnkrankheiten fur
      Aerzte and Studirende' (1881) with a commentary.
AB  - AIMS: A translation into English of the case history section of Carl Wernicke's
      original manuscript of 1881, with a discussion on its relevance for clinicians
      today. METHODS: A copy of Carl Wernicke's original German text was obtained by
      one of the authors (CCHC) and translated into English from the old German by a
      professional translator. RESULTS: The translation was subsequently agreed by
      native German speaking referees, and minor changes made. CONCLUSIONS: The authors
      studied the translation in detail and concluded that Wernicke's description had
      stood the test of time. The diagnosis of Wernicke's Encephalopathy remains a
      clinical one.

PMID- 18056752
TI  - Interventions used by physical therapists in home care for people after hip
      fracture.
AB  - BACKGROUND AND PURPOSE: The majority of older people who survive a hip fracture
      have residual mobility disabilities. Any attempt to systematically reduce
      mobility disabilities after hip fracture, however, requires knowledge of the
      adequacy of current management practices. Therefore, the purpose of this study
      was to begin to understand the nature of physical therapy home care management by
      describing "usual care" for people after hip fracture. SUBJECTS AND METHODS: In
      2003 and 2004, a national survey was conducted of all members of the American
      Physical Therapy Association who identified home care as their primary practice
      setting (n=3,130). "Usual care" was operationally defined as when more than 50%
      of respondents reported that they "always" or "often" use a specific
      intervention. RESULTS: Survey questionnaires (1,029) were returned with a
      response rate of 32.9%. Functional training activities, including bed mobility,
      transfer and gait training, balance training, safety training, and patient
      education, were reported very frequently. Active-range-of-motion exercises were
      performed much more frequently than exercises involving added resistance.
      DISCUSSION AND CONCLUSION: This study provides a detailed description of the
      physical therapy interventions provided in the home care setting for patients
      after hip fracture. The sample size and national representation increase our
      confidence that this description accurately depicts physical therapist practice.

PMID- 18056753
TI  - Effects of education on return-to-work status for people with fear-avoidance
      beliefs and acute low back pain.
AB  - BACKGROUND AND PURPOSE: People with acute low back injury and fear-avoidance
      beliefs are at risk for remaining off work for an extended period of time.
      However, the effectiveness of intervention strategies for improving return-to
      work status in people with acute low back pain and fear-avoidance beliefs has not
      been reported. The objective of this study was to determine whether education and
      counseling on pain management, physical activity, and exercise could
      significantly decrease the number of days that people with low back injury are
      off work. SUBJECTS: Thirty-four people who were unable to return to work
      following a work-related episode of low back pain and who exhibited fear
      avoidance beliefs participated in this study. METHODS: Participants who scored 50
      points or higher on the Fear-Avoidance Beliefs Questionnaire were alternately
      assigned to an education group or a comparison group. Both groups received
      conventional physical therapy intervention. Participants in the education group
      were given education and counseling on pain management tactics and the value of
      physical activity and exercise. The effectiveness of the interventions was
      measured by the number of days before people returned to work without
      restrictions. RESULTS: All participants in the education group returned to
      regular work duties within 45 days. One third of the participants in the
      comparison group remained off work at 45 days. There was a statistically
      significant difference between the groups with regard to the number of days
      before returning to work. DISCUSSION AND CONCLUSION: Education and counseling
      regarding pain management, physical activity, and exercise can reduce the number
      of days off work in people with fear-avoidance beliefs and acute low back pain.

PMID- 18056754
TI  - Estimation of thigh muscle mass with magnetic resonance imaging in older adults
      and people with chronic obstructive pulmonary disease.
AB  - BACKGROUND AND PURPOSE: Quantifying muscle mass is an essential part of physical
      therapy assessment, particularly in older adults and in people with chronic
      conditions associated with muscle atrophy. The purposes of this study were to
      examine the relationship between muscle cross-sectional area (CSA) and volume by
      use of magnetic resonance imaging (MRI) and to compare anthropometric estimations
      of midthigh CSA with measurements obtained from MRI. SUBJECTS AND METHODS: Twenty
      older adults who were healthy and 20 people with chronic obstructive pulmonary
      disease (COPD), matched for age, sex, and body mass index, underwent MRI to
      obtain measurements of thigh muscle CSA and volume. Anthropometric measurements
      (skinfold thickness and thigh circumference) were used to estimate midthigh CSA.
      RESULTS: Muscle volumes were significantly lower in the people with COPD than in
      the older adults who were healthy. Moderate to high correlations were found
      between midthigh CSA and volume in both groups (r=.61-.94). Anthropometric
      measurements tended to overestimate midthigh CSA in both the people with COPD
      (estimated CSA=64.9+/-17.8; actual CSA=48.3+/-10.2 cm(2)) and the older adults
      who were healthy (estimated quadriceps femoris muscle CSA=65.0+/-14.0; actual
      CSA=56.8+/-13.5 cm(2)). Furthermore, the estimated quadriceps femoris muscle CSAs
      were not sensitive enough to detect a difference in muscle size between people
      with COPD and controls. Thigh circumference alone was not different between
      groups and showed only low to moderate correlations with muscle volume (r=.19
      .47). DISCUSSION AND CONCLUSION: Muscle CSA measured from a single slice provides
      a good indication of volume, but the most representative slice should be chosen
      on the basis of the muscle group of interest. Thigh circumference is not
      correlated with muscle volume and, therefore, should not be used as an indicator
      of muscle size. The development of population-specific reference equations for
      estimating muscle CSA from anthropometric measurements is warranted.

PMID- 18056755
TI  - Adalimumab effectively reduces the signs and symptoms of active ankylosing
      spondylitis in patients with total spinal ankylosis.
AB  - OBJECTIVE: To evaluate the long-term safety and efficacy of adalimumab in
      patients with ankylosing spondylitis (AS) and total spinal ankylosis (TSA).
      DESIGN: Patients (n = 315) with active AS were randomised in a 2:1 ratio to
      receive adalimumab 40 mg every other week or placebo for 24 weeks followed by
      open-label adalimumab for up to 5 years. Two-year efficacy and safety data for 11
      patients with investigator-defined TSA were evaluated. The primary end point was
      the ASsessment in AS International Working Group criteria for 20% improvement
      (ASAS20) at Week 12. On or after Week 12, ASAS20 non-responders could switch to
      open-label adalimumab. Other efficacy measurements included ASAS40, ASAS 5/6,
      ASAS partial remission, and 50% improvement in the Bath AS Disease Activity Index
      (BASDAI 50). RESULTS: 6 of 11 TSA patients were randomised to adalimumab and 5 to
      placebo. At Week 12, 50% of the adalimumab-treated patients achieved an ASAS20
      response and 33% achieved an ASAS40, ASAS 5/6 and BASDAI 50. No placebo-treated
      patients achieved any response criteria at Week 12. 4 placebo- and 2 adalimumab
      treated patients switched to open-label adalimumab before Week 24. After 1 year
      of adalimumab treatment, 8 of 11 patients achieved an ASAS20 response. After 2
      years, 6 of the remaining 8 patients with TSA reported an ASAS20 response. There
      were no serious adverse events or adverse event-related study discontinuations.
      CONCLUSION: In patients with TSA, adalimumab treatment resulted in rapid and
      clinically significant improvement in the signs and symptoms of active disease.
      Adalimumab effectiveness and safety were sustained for at least 2 years. TRIAL
      REGISTRATION NUMBER: NCT00085644.

PMID- 18056756
TI  - Modulation of established murine collagen-induced arthritis by a single
      inoculation of short-term lipopolysaccharide-stimulated dendritic cells.
AB  - BACKGROUND: The use of regulatory or immature dendritic cells (DCs) as tools for
      modulating experimental rheumatoid arthritis is very recent. Tumour necrosis
      factor (TNF)-stimulated DCs have been shown to restore tolerance in experimental
      autoimmune encephalomyelitis and collagen-induced arthritis (CIA). OBJECTIVE: We
      investigated the capacity of short-term lipopolysaccharide (LPS)-stimulated DCs
      pulsed with type II collagen (CII) to induce tolerance against established CIA.
      METHODS: Bone marrow-derived DCs were generated in the presence of granulocyte
      monocyte colony-stimulating factor (GM-CSF). After CIA induction, mice were
      injected at day 35 with a single dose of 4- or 24-h LPS-stimulated DCs that had
      been loaded with CII (4hLPS/CII/DCs or 24hLPS/CII/DCs). Arthritis progression was
      monitored by clinical and histological evaluations. RESULTS: Flow cytometry of
      4hLPS/CII/DCs showed intermediate CD40 and CD86 expression, lower than that of
      24hLPS/CII/DCs (fully mature) and higher than that of CII/DCs (immature). A
      functional assay showed that 4hLPS/CII/DCs display increased endocytosis ability
      with respect to 24hLPS/CII/DCs, indicating a semimature state. The single
      inoculation of 4hLPS/CII/DCs in mice with established CIA reduced disease
      severity significantly over time. Histological evaluation of mice treated with
      4hLPS/CII/DCs revealed diminished inflammatory synovitis, cartilage damage and
      fibrosis. Co-cultures of DCs with splenocytes from CIA mice showed that collagen
      specific interferon (IFN)gamma production was dramatically inhibited by
      4hLPS/CII/DCs. 4hLPS/CII/DCs were high IL10 producers, which could explain the
      inhibition of arthritis progression in mice receiving this treatment because
      neither antibodies nor regulatory CD4+CD25+Foxp3+ T lymphocytes were demonstrated
      to be involved. CONCLUSION: Short-term LPS-modulated DCs inoculation interferes
      with CIA progression when loaded with CII.

PMID- 18056757
TI  - The metastasis associated protein S100A4: a potential novel link to inflammation
      and consequent aggressive behaviour of rheumatoid arthritis synovial fibroblasts.
AB  - The metastasis-associated protein S100A4 belongs to the large family of S100
      calcium-binding proteins that appear to play regulatory roles in diverse
      biological activities. Moreover, a prognostic role of S100A4 has been suggested
      for patients with several types of cancer. Cancer promoting properties for S100A4
      have been demonstrated, particularly through its regulation of cell motility,
      proliferation and apoptosis, as well as by stimulation of angiogenesis and
      remodelling of the extracellular matrix. Increased expression of S100A4 mRNA has
      been detected in proliferating synovial fibroblasts in rheumatoid arthritis.
      Furthermore, strong upregulation of the S100A4 protein in rheumatoid arthritis
      synovial tissue compared with osteoarthritis and control tissues has been
      demonstrated recently, especially at sites of joint invasion. Several immune and
      vascular cells were also identified to be producing S100A4 within the synovium.
      The local upregulation of S100A4 was accompanied by high plasma and synovial
      fluid concentrations of the S100A4 protein existing in the bioactive oligomeric
      form in patients with rheumatoid arthritis. Consistent with data from cancer
      studies, the extracellular S100A4 oligomer appears to be involved in regulation
      of several matrix-degrading enzymes and modulation of the transcriptional
      activation function of the tumour suppressor protein p53 in rheumatoid arthritis
      synovial fibroblasts. Taken together, one can speculate that increased S100A4
      protein in circulation and locally at sites of inflammation, particularly at
      sites of joint destruction, might be linked to the process of aggressive
      fibroblast behaviour contributing to the pathogenesis of chronic autoinflammatory
      diseases such as rheumatoid arthritis.

PMID- 18056758
TI  - Major genetic components underlying alcoholism in Korean population.
AB  - Alcohol metabolism is one of the biological determinants that could significantly
      be influenced by genetic polymorphisms in alcohol-metabolism genes. Alcohol
      dehydrogenase (ADH) converts alcohol to acetaldehyde, and aldehyde dehydrogenase
      (ALDH) converts acetaldehyde to acetate. The well-known genetic polymorphisms in
      ADH1B(His47Arg) and ALDH2(Glu487Lys) have dramatic effects on the rate of
      metabolizing alcohol and acetaldehyde, respectively. The protective allele of
      ADH1B (ADH1B*47His) encodes for a rapid ethanol-metabolizing enzyme, and the
      susceptible allele of the ALDH2 (ALDH2*487Lys) is strongly associated with
      decreased rate of metabolizing acetaldehyde. However, the combined genetic
      effects of both functional polymorphisms have not been clarified. The combined
      analysis of two polymorphisms among a Korean population (n = 1,032) revealed
      dramatic genetic effects on the risk of alcoholism. Individuals bearing
      susceptible alleles at both loci have 91 times greater risk for alcoholism [odds
      ratio (OR) = 91.43, P = 1.4 x 10(-32)] and individuals bearing one susceptible
      and one protective allele at either loci have 11 times greater risk (OR = 11.40,
      P = 3.5 x 10(-15)) compared with subjects who have both protective alleles. The
      attributable fraction of those genetic factors, calculated based on population
      controls, indicates that alcoholism in 86.5% of alcoholic patients can be
      attributed to the detrimental effect of ADH1B*47Arg and/or ALDH2*487Glu in Korean
      population.

PMID- 18056759
TI  - Circulating smooth muscle progenitor cells: novel players in plaque stability.

PMID- 18056760
TI  - The effect of cholesteryl ester transfer protein overexpression and inhibition on
      reverse cholesterol transport.
AB  - AIMS: Cholesteryl ester transfer protein (CETP) has a well-established role in
      lipoprotein metabolism, but the effect of its overexpression or inhibition on the
      efficiency of reverse cholesterol transport (RCT) is unclear. METHODS AND
      RESULTS: Neither overexpression of CETP nor treatment with CETP inhibitor
      Torcetrapib of RAW 264.7 macrophages or HepG2 hepatocytes affected cholesterol
      efflux in vitro. Overexpression of CETP or treatment with Torcetrapib,
      respectively, stimulated or inhibited HDL cholesteryl ester uptake by HepG2 but
      not by RAW 264.7 cells. When RAW 264.7 cells transfected with CETP or ATP binding
      cassette transporter A1 (ABCA1) were injected intraperitoneally into mice,
      cholesterol egress from macrophages was elevated for ABCA1- but not for CETP
      transfected macrophages. Systemic expression of CETP in mice by adenoviral
      infection stimulated egress of cholesterol to plasma and liver without affecting
      HDL levels. Treatment with Torcetrapib did not affect appearance of macrophage
      cholesterol in plasma and liver, but inhibited its excretion into feces.
      Treatment of hamsters with Torcetrapib led to elevation of HDL cholesterol, an
      increase in the capacity of plasma to support cholesterol efflux, and increased
      egress of cholesterol from macrophages to plasma and feces in vivo. CONCLUSION:
      Both increased (mice study) and decreased (hamster study) CETP activity could
      result in enhanced RCT.

PMID- 18056761
TI  - Mechanisms underlying increased right ventricular conduction sensitivity to
      flecainide challenge.
AB  - AIMS: The cardiac sodium current (I(Na)) is a major determinant of conduction.
      Mechanisms underlying regionally heterogeneous conduction slowing secondary to
      reduced I(Na) in diseases such as the Brugada syndrome and heart failure remain
      incompletely understood. Right precordial electrophysiological manifestations
      during flecainide challenge suggest a decreased right ventricular depolarization
      reserve. We hypothesized that heterogeneous cardiac sodium channel (Na(v)1.5)
      distribution between ventricles causes interventricular depolarization
      heterogeneities. METHODS AND RESULTS: Western blotting analysis revealed
      Na(v)1.5, and Kir2.1 protein expressions were 18.2 and 12.0% lower, respectively,
      in the guinea pig right ventricle (RV) compared with the left ventricle (LV).
      Conduction velocity (theta) heterogeneities were quantified by optical mapping
      during LV or RV pacing. Although RV transverse theta((thetaT)) was significantly
      greater than LV (thetaT) by 33.09 +/- 1.38% under control conditions, there were
      no differences in longitudinal theta. During partial sodium channel blockade
      (flecainide, 0.5 microM), RV theta decreased by 35.3 +/- 1.3%, whereas LV theta
      decreased by 29.2 +/- 1.0%. These data demonstrate that the RV has an increased
      conduction dependence on sodium channel availability. Partial blockade of the
      inward rectifier potassium current (I(K1)) by BaCl(2) (10 microm) significantly
      increased theta in both ventricles under control conditions. However, BaCl(2)
      only increased conduction dependence on sodium channel availability in the LV.
      This suggests that the LV may have an increased depolarization reserve compared
      with the RV, but the larger I(K1) depresses control LV theta. CONCLUSION:
      Interventricular I(K1) heterogeneities may underlie conduction heterogeneities
      observed under control conditions. However, under conditions where I(Na) is
      functionally reduced in disease or during pharmacological sodium channel
      blockade, the heterogeneity in Na(v)1.5 expression may become a significant
      determinant of conduction heterogeneities.

PMID- 18056762
TI  - Dystrophic cardiomyopathy: amplification of cellular damage by Ca2+ signalling
      and reactive oxygen species-generating pathways.
AB  - AIMS: Cardiac myopathies are the second leading cause of death in patients with
      Duchenne and Becker muscular dystrophy, the two most common and severe forms of a
      disabling striated muscle disease. Although the genetic defect has been
      identified as mutations of the dystrophin gene, very little is known about the
      molecular and cellular events leading to progressive cardiac muscle damage.
      Dystrophin is a protein linking the cytoskeleton to a complex of transmembrane
      proteins that interact with the extracellular matrix. The fragility of the cell
      membrane resulting from the lack of dystrophin is thought to cause an excessive
      susceptibility to mechanical stress. Here, we examined cellular mechanisms
      linking the initial membrane damage to the dysfunction of dystrophic heart.
      METHODS AND RESULTS: Cardiac ventricular myocytes were enzymatically isolated
      from 5- to 9-month-old dystrophic mdx and wild-type (WT) mice. Cells were exposed
      to mechanical stress, applied as osmotic shock. Stress-induced cytosolic and
      mitochondrial Ca(2+) signals, production of reactive oxygen species (ROS), and
      mitochondrial membrane potential were monitored with confocal microscopy and
      fluorescent indicators. Pharmacological tools were used to scavenge ROS and to
      identify their possible sources. Osmotic shock triggered excessive cytosolic
      Ca(2+) signals, often lasting for several minutes, in 82% of mdx cells. In
      contrast, only 47% of the WT cardiomyocytes responded with transient and moderate
      intracellular Ca(2+) signals. On average, the reaction was 6-fold larger in mdx
      cells. Removal of extracellular Ca(2+) abolished these responses, implicating
      Ca(2+) influx as a trigger for abnormal Ca(2+) signalling. Our further
      experiments revealed that osmotic stress in mdx cells produced an increase in ROS
      production and mitochondrial Ca(2+) overload. The latter was followed by collapse
      of the mitochondrial membrane potential, an early sign of cell death. CONCLUSION:
      Overall, our findings reveal that excessive intracellular Ca(2+) signals and ROS
      generation link the initial sarcolemmal injury to mitochondrial dysfunctions. The
      latter possibly contribute to the loss of functional cardiac myocytes and heart
      failure in dystrophy. Understanding the sequence of events of dystrophic cell
      damage and the deleterious amplification systems involved, including several
      positive feed-back loops, may allow for a rational development of novel
      therapeutic strategies.

PMID- 18056763
TI  - Non-canonical fibroblast growth factor signalling in angiogenesis.
AB  - Whereas fibroblast growth factors (FGFs) classically transmit their signals via
      high-affinity tyrosine kinase receptors (FGFR1-4), recent evidence strongly
      implicates non-tyrosine kinase receptors (NTKR) or cell-surface FGFR-interacting
      proteins as important players in FGF signalling. Although NTKR have lower
      affinity for FGFs in comparison with cognate tyrosine kinase receptors, because
      of their high abundance they can effectively bind FGFs and produce unique
      biological effects independent of FGFRs. A prime example of such NTKR is the
      syndecan family of plasma membrane proteoglycans and, in particular, syndecan-4,
      which transmits FGF signalling via a protein kinase Calpha pathway. Another NTKR,
      alpha(v)beta(3) integrin, functions as an FGF signalling modulator by binding
      both FGF2 and FGFR1. Yet another NTKR, neural cell adhesion molecule (NCAM), can
      serve as an FGFR ligand and assemble an FGFR signalling complex in the absence of
      FGFs. Furthermore, N-cadherin, which has been reported to associate with FGFR,
      appears to activate FGFR in both ligand (FGF)-dependent and ligand-independent
      manners. Finally, gangliosides are implicated as a co-receptor system of FGFs.
      The biological consequence of non-canonical FGF signalling tends to be less
      discernable compared to the canonical FGFR activation because of the overlap
      between these two pathways; nevertheless, non-canonical signalling is important
      and sometimes essential for cellular functions. Given the diversity of FGF
      activities through embryonic development to adult physiology, the existence of
      the non-canonical signalling system may account for the different cellular
      response to the FGF input in different biological contexts. In this review, we
      will discuss recent findings related to non-canonical FGF signalling with
      emphasis on the endothelial biology and angiogenesis.

PMID- 18056764
TI  - Protein kinase C alpha promotes angiogenic activity of human endothelial cells
      via induction of vascular endothelial growth factor.
AB  - AIMS: Protein kinase C (PKC) plays an important role in the regulation of
      angiogenesis. However, downstream targets of PKC in endothelial cells are poorly
      defined. METHODS AND RESULTS: mRNA expression of vascular endothelial growth
      factor (VEGF) was analysed by quantitative real-time RT-PCR in human umbilical
      vein endothelial cells (HUVEC) and HUVEC-derived EA.hy 926 cells. siRNA was used
      to knockdown PKC isoforms and VEGF. Matrigel tube formation assay was used to
      analyse the angiogenic activity of endothelial cells. Phorbol-12-myristate-13
      acetate (PMA) enhanced the ability of HUVEC to organize into tubular networks
      when plated on Matrigel, a phenomenon that could be prevented by PKC inhibitors.
      PMA markedly increased the expression of VEGF in HUVEC and EA.hy 926 cells. The
      enhancement in VEGF expression was prevented by PKC inhibitors and by an
      inhibitor of the Erk1/2 pathway. PMA-induced tube formation was reduced by
      inhibition of the VEGF receptor kinase, or by VEGF knockdown. PMA led to an
      activation of PKC isoforms alpha, delta and epsilon in HUVEC. Knockdown of PKC
      alpha diminished PMA-induced VEGF expression and angiogenesis. Also endothelial
      progenitor cells isolated from human peripheral blood showed enhanced VEGF
      expression and improved angiogenic activity in response to PKC activation.
      Moreover, incubation of HUVEC with VEGF led to PKC alpha activation and PKC
      dependent VEGF upregulation. CONCLUSIONS: PKC alpha activation promotes
      angiogenic activity of human endothelial cells. This is likely to be largely
      mediated by induction of VEGF. VEGF enhances its own expression via a PKC alpha
      dependent positive feedback mechanism.

PMID- 18056765
TI  - Sarcomeric proteins and inherited cardiomyopathies.
AB  - Over the last two decades, a large number of mutations have been identified in
      sarcomeric proteins as a cause of hypertrophic, dilated or restrictive
      cardiomyopathy. Functional analyses of mutant proteins in vitro have revealed
      several important functional changes in sarcomeric proteins that might be
      primarily involved in the pathogenesis of each cardiomyopathy. Creation of
      transgenic or knock-in animals expressing mutant proteins in their hearts
      confirmed that these mutations in genes for sarcomeric proteins induced distinct
      types of cardiomyopathies and provided useful animal models to explore the
      molecular pathogenic mechanisms and potential therapeutics of cardiomyopathy in
      vivo. In this review, I discuss the functional consequences of mutations in
      different sarcomeric proteins found in hypertrophic, dilated, and restrictive
      cardiomyopathies in conjunction with their effects on cardiac structure and
      function in vivo and their possible molecular and cellular mechanisms, which
      underlie the pathogenesis of these inherited cardiomyopathies.

PMID- 18056766
TI  - Gap junction remodelling in human heart failure is associated with increased
      interaction of connexin43 with ZO-1.
AB  - AIMS: Remodelling of gap junctions, involving reduction of total gap junction
      quantity and down-regulation of connexin43 (Cx43), contributes to the arrhythmic
      substrate in congestive heart failure. However, little is known of the underlying
      mechanisms. Recent studies from in vitro systems suggest that the connexin
      interacting protein zonula occludens-1 (ZO-1) is a potential mediator of gap
      junction remodelling. We therefore examined the hypothesis that ZO-1 contributes
      to reduced expression of Cx43 gap junctions in congestive heart failure. METHODS
      AND RESULTS: Left ventricular myocardium from healthy control human hearts (n =
      5) was compared with that of explanted hearts from transplant patients with end
      stage congestive heart failure due to idiopathic dilated cardiomyopathy (DCM; n =
      5) or ischaemic cardiomyopathy (ICM; n = 5). Immunoconfocal and immunoelectron
      microscopy showed that ZO-1 is specifically localized to the intercalated disc of
      cardiomyocytes in control and failing ventricles. ZO-1 protein levels were
      significantly increased in both DCM and ICM (P = 0.0025), showing a significant,
      negative correlation to Cx43 levels (P = 0.0029). There was, however, no
      significant alteration of ZO-1 mRNA (P = 0.537). Double immunolabelling
      demonstrated that a proportion of ZO-1 label is co-localized with Cx43, and that
      co-localization of Cx43 with ZO-1 is significantly increased in the failing
      ventricle (P = 0.003). Interaction between the two proteins was confirmed by co
      immunoprecipitation. The proportion of Cx43 that co-immunoprecipitates with ZO-1
      was significantly increased in the failing heart. CONCLUSION: Our findings
      suggest that ZO-1, by interacting with Cx43, plays a role in the down-regulation
      and decreased size of Cx43 gap junctions in congestive heart failure.

PMID- 18056767
TI  - Effect of acidic reperfusion on prolongation of intracellular acidosis and
      myocardial salvage.
AB  - AIMS: It has been proposed that intracellular acidosis may be the basis of the
      cardioprotection of different interventions, including postconditioning. However,
      contradictory reports exist on the effects of acidic reperfusion on myocardial
      salvage. Here we characterized the effect of lowering the pH of the reperfusion
      media (pHo) on intracellular pH (pHi) and cell death. METHODS AND RESULTS: The
      effect of acidic perfusion on reperfusion injury was studied in isolated rat
      hearts submitted to 40 min of ischaemia and 30 min of reperfusion, and its effect
      on the Na(+)/Ca(2+)-exchanger (NCX) was analysed in isolated myocytes. pHi and
      phosphocreatine (PCr) were monitored by nuclear magnetic resonance spectroscopy.
      Lowering pHo to 6.4 during the initial 3 min of reperfusion delayed pHi
      normalization, improved PCr recovery, and markedly reduced (P < 0.001) lactate
      dehydrogenase release and infarct size (tetrazolium reaction). This
      cardioprotection was attenuated as pHo was increased, and was lost at pH0 7.0.
      Extending acidic reperfusion to the first 15 or 30 min of reflow did not result
      in further delay of pHi normalization and abolished the protection afforded by
      the initial 3 min of acidic reperfusion unless the Na(+)/H(+)-exchanger (NHE)
      blocker cariporide was added to the acidic perfusate and HCO(3)(-) substituted
      for N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulphonic acid]. In experiments
      performed in fura-2-loaded myocytes exposed to low Na(+) buffer adjusted to pH
      6.4, the lower Ca(2+) uptake indicated an inhibitory effect of acidosis on NCX.
      CONCLUSION: Acidic reperfusion for 3 min delays normalization of pHi and enhances
      myocardial salvage, but extending it beyond this period fails to further delay
      pHi recovery. This is probably due to persisting NHE and Na(+)/HCO(3)(-)
      cotransporter activities, and it is detrimental, possibly through prolonged NCX
      inhibition.

PMID- 18056768
TI  - Ligand-dependent activation of ER{beta} lowers blood pressure and attenuates
      cardiac hypertrophy in ovariectomized spontaneously hypertensive rats.
AB  - AIMS: The biological effects of oestrogens are mediated by two different
      oestrogen receptor (ER) subtypes, ERalpha and ERbeta, which might play different,
      redundant, or opposing roles in cardiovascular disease. Previously, we have shown
      that the selective ERalpha agonist 16alpha-LE2 improves vascular relaxation,
      attenuates cardiac hypertrophy, and increases cardiac output without lowering
      elevated blood pressure in spontaneously hypertensive rats (SHR). Because ERbeta
      deficient mice exhibit elevated blood pressure and since the ERbeta agonist 8beta
      VE2 attenuated hypertension in aldosterone-salt-treated rats, we have now tested
      the hypothesis that the isotype-selective ERbeta agonist 8beta-VE2 might be
      capable of lowering elevated blood pressure in ovariectomized SHR. METHODS AND
      RESULTS: Treatment of ovariectomized SHR with 8beta-VE2 for 12 weeks conferred no
      uterotrophic effects but lowered elevated systolic blood pressure (-38 +/- 5
      mmHg, n = 31, P < 0.001 vs. placebo) as well as peripheral vascular resistance (
      31.3 +/- 4.6%, P < 0.001 vs. placebo). 8beta-VE2 enhanced aortic ERbeta
      expression (+75.7 +/- 7.1%, P < 0.01 vs. placebo), improved NO-dependent
      vasorelaxation, augmented phosphorylation of the vasodilator-stimulated
      phosphoprotein in isolated aortic rings (P < 0.05 vs. placebo), increased cardiac
      output (+20.4 +/- 2.5%, P < 0.01 vs. placebo), and attenuated cardiac hypertrophy
      (-22.2 +/- 3.2%, p < 0.01 vs. placebo). 8beta-VE2, in contrast to oestradiol, did
      not enhance cardiac alpha-myosin heavy chain expression. CONCLUSION: Ligand
      dependent activation of ERbeta confers blood pressure lowering effects in SHR
      that are superior to those of 17beta-estradiol or the ERalpha agonist 16alpha-LE2
      and attenuates cardiac hypertrophy primarily by a reduction of cardiac afterload
      without promoting uterine growth.

PMID- 18056770
TI  - Late recurrences of Cushing's disease after initial successful transsphenoidal
      surgery.
AB  - CONTEXT: Few studies have systematically analyzed the long-term recurrence rates
      of Cushing's disease after initial successful transsphenoidal surgery. SETTING:
      This was a retrospective review of patients treated at the University of Virginia
      Medical Center. PATIENTS: A total of 215 subjects with Cushing's disease who
      underwent initial transsphenoidal surgery for resection of a presumed pituitary
      microadenoma from 1992-2006 were included. MAIN OUTCOME MEASURES: Remission and
      recurrence rates of Cushing's disease were examined. Recurrence was defined as an
      elevated 24-h urine free cortisol with clinical symptoms consistent with
      Cushing's disease. RESULTS: Of the 215 patients who underwent transsphenoidal
      surgery for Cushing's disease, surgical remission was achieved in 184 (85.6%).
      The mean length of follow-up was 45 months. Actuarial recurrence rates of
      Cushing's disease after initially successful transsphenoidal surgery at 1, 2, 3,
      and 5 yr were 0.5, 6.7, 10.8, and 25.5%, respectively. Among the 184 patients who
      achieved remission, 32 (17.4%) patients followed for more than 6 months
      ultimately had a recurrence of Cushing's disease. The median time to recurrence
      was 39 months. Immediate postoperative hypocortisolemia (serum cortisol < or = 2
      microg/dl within 72-h surgery) was achieved in 97 (45.1%) patients. Patients who
      had postoperative serum cortisol of more than 2 microg/dl were 2.5 times more
      likely to have a recurrence than patients who had serum cortisol less than or
      equal to 2 microg/dl (odds ratio = 2.5; 95% confidence interval 1.12-5.52; P =
      0.022). CONCLUSIONS: A quarter of the patients with Cushing's disease who achieve
      surgical remission after transsphenoidal surgery, recur with long-term follow-up.
      This finding emphasizes the need for continued biochemical and clinical follow-up
      to ensure remission after surgery.

PMID- 18056769
TI  - Effects of continuous versus cyclical oral contraception: a randomized controlled
      trial.
AB  - CONTEXT: Continuous oral contraception may better suppress the ovary and
      endometrium, lending itself to the treatment of other medical conditions.
      OBJECTIVE: Our objective was to determine the effects of continuous vs. cyclical
      oral contraception. DESIGN: This was a randomized double-blind trial. SETTING:
      This trial was performed at an academic medical center in Pennsylvania. PATIENTS:
      A total of 62 healthy women with regular menses were included in the study.
      INTERVENTION: Cyclical oral contraception (21-d active/7-d placebo given for six
      consecutive 28-d cycles) vs. continuous (168-d active pill) therapy using a
      monophasic pill (20 microg ethinyl estradiol and 1 mg norethindrone acetate) was
      examined. MAIN OUTCOME MEASURES: The primary outcome was vaginal bleeding, and
      secondary outcomes included hormonal, pelvic ultrasound, quality of life, and
      safety measures. RESULTS: There was no statistically significant difference in
      the number of total bleeding days between groups, but moderate/heavy bleeding was
      significantly greater with the cyclical regimen [mean 11.0 d (sd 8.5) vs.
      continuous 5.2 d (sd 6.8); P = 0.005], with both groups decreasing over time.
      Endogenous serum and urinary estrogens measured over six cycles were
      significantly lower (P = 0.02 and 0.04, respectively) in the continuous group
      than the cyclical group. Women in the continuous group also had a smaller ovarian
      volume and lead follicle size over the course of the trial by serial ultrasound
      examinations. The Moos Menstrual Distress Questionnaire showed that women on
      continuous therapy had less associated menstrual pain (P = 0.01) and favorable
      improvements in behavior (P = 0.04) during the premenstrual period. CONCLUSIONS:
      Continuous oral contraception does not result in a reduction of bleeding days
      over a 168-d period of observation but provides greater suppression of the ovary
      and endometrium. These effects are associated with improved patient
      symptomatology.

PMID- 18056771
TI  - An immortalized human cell line bearing a PRKAR1A-inactivating mutation: effects
      of overexpression of the wild-type Allele and other protein kinase A subunits.
AB  - CONTEXT: Inactivating mutations of PRKAR1A, the regulatory subunit type 1A
      (RIalpha) of protein kinase A (PKA), are associated with tumor formation.
      OBJECTIVE: Our objective was to evaluate the role of PKA isozymes on
      proliferation and cell cycle. METHODS: A cell line with RIalpha
      haploinsufficiency due to an inactivating PRKAR1A mutation (IVS2+1 G-->A) was
      transfected with constructs encoding PKA subunits. Genetics, PKA subunit mRNA and
      protein expression and proliferation, aneuploidy, and cell cycle status were
      assessed. To identify factors that mediate PKA-associated cell cycle changes, we
      studied E2F and cyclins expression in transfected cells and E2F's role by small
      interfering RNA; we also assessed cAMP levels and baseline and stimulated cAMP
      signaling in transfected cells. RESULTS: Introduction of PKA subunits led to
      changes in proliferation and cell cycle: a decrease in aneuploidy and G(2)/M for
      the PRKAR1A-transfected cells and an increase in S phase and aneuploidy for cells
      transfected with PRKAR2B, a known PRKAR1A mutant (RIalphaP), and the PKA
      catalytic subunit. There were alterations in cAMP levels, PKA subunit expression,
      cyclins, and E2F factors; E2F1 was shown to possibly mediate PKA effects on cell
      cycle by small interfering RNA studies. cAMP levels and constitutive and
      stimulated cAMP signaling were altered in transfected cells. CONCLUSION: This is
      the first immortalized cell line with a naturally occurring PRKAR1A-inactivating
      mutation that is associated in vivo with tumor formation. PKA isozyme balance is
      critical for the control of cAMP signaling and related cell cycle and
      proliferation changes. Finally, E2F1 may be a factor that mediates dysregulated
      PKA's effects on the cell cycle.

PMID- 18056772
TI  - A more atherogenic serum lipoprotein profile is present in women with polycystic
      ovary syndrome: a case-control study.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is associated with a higher frequency
      of cardiovascular risk factors. Apolipoprotein (apo) A-I and apoB are potent
      markers for cardiovascular risk. Data on apo levels in women with PCOS are scarce
      and contradictory. OBJECTIVE: Our objective was to identify changes in lipid
      metabolism in women with PCOS, and the relative impact of obesity, insulin
      resistance, and hyperandrogenism on lipid parameters. DESIGN: This was a case
      control study. SETTING: The study was performed at a single referral center.
      SUBJECTS: PCOS was diagnosed according to the 2003 Rotterdam criteria. Healthy
      mothers with regular menstrual cycles served as controls. MAIN OUTCOME
      PARAMETERS: Fasting insulin, triglycerides (TGs), cholesterol, high-density
      lipoprotein (HDL)-cholesterol, apoA-I, and apoB were determined. Low-density
      lipoprotein (LDL)-cholesterol was calculated using the Friedewald formula.
      RESULTS: We included 557 women with PCOS and 295 controls. After correction for
      age and body mass index, PCOS women had higher median levels of insulin (10.1 vs.
      6.9 mU/liter), TGs (95 vs. 81 mg/dl), cholesterol (196 vs. 178 mg/dl), and LDL
      cholesterol (125 vs. 106 mg/dl) in combination with lower levels of HDL
      cholesterol (46 vs. 55 mg/dl) and apoA-I (118 vs. 146 mg/dl) compared with
      controls (all P values < or = 0.01). apoB levels were similar in cases and
      controls. Free androgen index, body mass index, SHBG, and estradiol were
      independent predictors of apoA-I levels in women with PCOS. CONCLUSIONS: PCOS is
      associated with a more pronounced atherogenic lipid profile. Furthermore, obesity
      and hyperandrogenism contribute to an adverse lipid profile. Finally, PCOS seems
      to constitute an additional risk factor for an atherogenic lipid profile.

PMID- 18056773
TI  - Determinants of skeletal age deviation in a cross-sectional study.
AB  - OBJECTIVE: Skeletal age deviation (SAD) is associated with bone mass and fracture
      risk in children, but factors determining this are unknown. The aim of this
      population-based cross-sectional study was to describe the factors associated
      with SAD. METHODS: A convenience sample of 640 male and female children aged 7-17
      yr was studied. All were assessed for body composition (dual-energy x-ray
      absorptiometry), diet, strength, dexterity, habitual physical activity, sunlight
      exposure, smoking, and medication use. Skeletal age was assigned using the Tanner
      Whitehouse-2 method. RESULTS: Subjects with a SAD greater than the 75th
      percentile had significantly higher height, weight, and Tanner stage compared
      with all other subjects. Bone-free lean mass, fat mass, and grip strength were
      positively associated with SAD. In multivariate analysis, ever smoking and use of
      inhaled corticosteroids were negatively associated with SAD, whereas milk
      drinking was positively associated with SAD. There was no significant association
      between sunlight exposure, television watching, light, or strenuous exercise and
      SAD. CONCLUSIONS: The results of this study should be regarded as hypothesis
      generating but are biologically plausible and suggest that body composition,
      strength, diet, ever smoking, and inhaled corticosteroid use may be determinants
      of bone maturity relative to age and thus affect fracture risk in children.
      However, more studies are necessary to explore other determinants of SAD such as
      genetic and perinatal factors and whether SAD influences peak bone mass.

PMID- 18056774
TI  - XX Maleness and XX true hermaphroditism in SRY-negative monozygotic twins:
      additional evidence for a common origin.
AB  - CONTEXT: Differentiation of testicular tissue in 46,XX individuals is seen either
      in XX males, the majority of them with SRY gene, or in individuals, usually SRY(
      ), with ovotesticular disorder of sex development (OT-DSD). Although they are
      sporadic cases, there are some reports on familial recurrence, including
      coexistence of XX maleness and OT-DSD in the same family. OBJECTIVE: We report on
      a case of SRY(-) 46,XX monozygotic twins with genital ambiguity. METHODS:
      Hormonal evaluation included testosterone, FSH, and LH measurements. SRY gene was
      investigated by PCR and two-step PCR in peripheral leukocytes and gonadal
      tissues, respectively. Direct DNA sequencing of the DAX-1 coding sequence was
      performed. Real-time PCR for SOX9 region on chromosome 17 was obtained. RESULTS:
      Both twins had a 46,XX karyotype. Twin A had a 1-cm phallus with chordee,
      penoscrotal hypospadias, and palpable gonads. Serum levels of FSH (2.34 mIU/ml),
      LH (8.8 mIU/ml), and testosterone (1.6 ng/ml) were normal, and biopsies revealed
      bilateral testes. Twin B had a 0.5-cm phallus, perineal hypospadias, no palpable
      gonad on the right, and a left inguinal hernia. Hormonal evaluation revealed high
      FSH (8.2 mIU/ml) and LH (15 mIU/ml) and low testosterone (0.12 ng/ml). Upon
      herniotomy, a right testis (crossed ectopia) and a small left ovotestis were
      found. SRY gene was absent in both peripheral leukocytes and gonadal tissue
      samples. Neither DAX-1 mutations nor SOX9 duplication was identified.
      CONCLUSIONS: This case provides evidence that both XX maleness and XX OT-DSD are
      different manifestations of the same disorder of gonadal development.

PMID- 18056776
TI  - Update in andrology.
AB  - CONTEXT: This is an invited review based on a presentation at the 2007 Annual
      Scientific Meeting of The Endocrine Society. OBJECTIVE: The objective of the
      review was to highlight a selection of the most important peer-reviewed papers in
      andrology published over the last 1-2 yr. EVIDENCE ACQUISITION: This was a
      comprehensive survey of all papers published in major endocrinology journals over
      the last 2 yr augmented by personal knowledge and literature searching as well as
      an e-mail survey of more than 40 leading andrologists. EVIDENCE SYNTHESIS: From
      the list of suggested papers, the findings of a short list considered the most
      important were reviewed, aiming to focus on findings that influence thinking and
      practice in the field of andrology. CONCLUSIONS: Important advances highlighted
      included establishing genetic paternity for men with Klinefelter's syndrome as a
      realistic therapeutic option via testicular sperm aspiration coupled with
      intracytoplasmic sperm injection in vitro fertilization, using population
      registry linkage data to define the natural history of Klinefelter's syndrome in
      the community and identifying active cellular uptake mechanisms for SHBG-bound
      testosterone challenging the quasiaxiomatic status of the free hormone
      hypothesis. Other important recent contributions reviewed are on testosterone
      effects on the prostate, hormonal male contraception, possible temporal trends in
      blood testosterone concentrations in American men, and The Endocrine Society's
      position papers on testosterone assays and guidelines on testosterone
      prescribing.

PMID- 18056775
TI  - Prolonged fasting induces peripheral insulin resistance, which is not ameliorated
      by high-dose salicylate.
AB  - CONTEXT: Elevated plasma free fatty acids, excess reactive oxygen species,
      inflammation, and gluco-counterregulatory hormones induce insulin resistance (IR)
      through activation of Jun NH(2)-terminal kinase and nuclear factor-kappaB
      inhibitor kappaB kinase, which leads to hyperphosphorylation of the insulin
      receptor substrate type 1. Aspirin blocks nuclear factor-kappaB inhibitor kappaB
      kinase and improves IR in type 2 diabetes mellitus. OBJECTIVE: We hypothesized
      that high-dose aspirin would also attenuate fasting-induced IR in healthy lean
      subjects. DESIGN: Glucose and glutathione (GHS) metabolism was studied after 12
      and 60 h of fasting on two occasions: with and without aspirin (6 g/d). SETTING:
      The study took place at the Academic Medical Center, Metabolic Research Unit.
      PARTICIPANTS: Six healthy lean men participated. INTERVENTION: Intervention
      included 60 h of fasting with or without aspirin ( approximately 6 g/d). MAIN
      OUTCOME MEASURE: Main outcome measures included glucose and GSH metabolism.
      RESULTS: Fasting decreased insulin-mediated peripheral glucose uptake by 46%
      after 60 h (P = 0.03). Aspirin did not alter this effect of 60 h of fasting on
      insulin sensitivity (P = 0.03). GSH concentration decreased during fasting, but
      the fractional synthetic rate of GSH was unaffected either with or without
      aspirin. Fasting did not affect inflammatory parameters, although aspirin
      increased soluble TNF receptors I and II. CONCLUSION: Prolonged fasting induces
      profound peripheral IR. In contrast to type 2 diabetes mellitus, high-dose
      salicylate does not affect fasting-induced peripheral IR.

PMID- 18056777
TI  - A Pulmonary adrenocorticotropin-secreting carcinoid tumor localized by 6-Fluoro
      [18F]L-dihydroxyphenylalanine positron emission/computed tomography imaging in a
      patient with Cushing's syndrome.

PMID- 18056778
TI  - Glucose intolerance in polycystic ovary syndrome--a position statement of the
      Androgen Excess Society.
AB  - OBJECTIVES: Women with polycystic ovarian syndrome (PCOS) are at increased risk
      for developing glucose intolerance and type 2 diabetes mellitus (DM).
      Recommendations for the timing and method of screening have varied. The purpose
      of this statement is to determine the optimal screening method, timing of
      screening, and treatment modalities for impaired glucose tolerance (IGT) among
      women with PCOS. PARTICIPANTS: The expert panel was appointed by the Androgen
      Excess Society (AES) to review the literature and make recommendations based on
      the available evidence. Meetings were open, and there was no funding for the
      panel. EVIDENCE: A systematic review was conducted of the published, peer
      reviewed medical literature using MEDLINE to identify studies that addressed the
      prevalence, risk factors, testing, and treatment for IGT in both adults and
      adolescents with PCOS. Unpublished data were not considered. CONSENSUS PROCESS:
      The panel held meetings to review the literature and draft the statement as a
      committee. The AES board members reviewed and critiqued the manuscript, and
      changes were made based on their comments. CONCLUSIONS: The panel recommends that
      all patients with PCOS be screened for IGT with a 2-h oral glucose tolerance
      test. A few members of the AES board recommend alternatively screening women with
      PCOS for IGT and type 2 DM using an oral glucose tolerance test only in patients
      with a body mass index of 30 kg/m2 or greater or in lean patients with additional
      risk factors. Patients with normal glucose tolerance should be rescreened at
      least once every 2 yr, or more frequently if additional risk factors are
      identified. Those with IGT should be screened annually for development of type 2
      DM. PCOS patients with IGT should be treated with intensive lifestyle
      modification and weight loss and considered for treatment with insulin
      sensitizing agents.

PMID- 18056779
TI  - Commentary on "increasing minority participation in clinical research": a white
      paper from the endocrine society.

PMID- 18056780
TI  - Upper limit of normal serum thyroid-stimulating hormone: a moving and now an
      aging target?

PMID- 18056781
TI  - Incretin hypersecretion in post-gastric bypass hypoglycemia--primary problem or
      red herring?

PMID- 18056782
TI  - Phenomics, lamin A/C, and metabolic disease.

PMID- 18056783
TI  - Map of differential transcript expression in the normal human large intestine.
AB  - While there is considerable research related to using differential gene
      expression to predict disease phenotype classification, e.g., neoplastic tissue
      from nonneoplastic controls, there is little understanding of the range of
      expression in normal tissues. Understanding patterns of gene expression in
      nonneoplastic tissue, including regional anatomic expression changes within an
      organ, is vital to understanding gene expression changes in diseased tissue. To
      explore the gene expression change along the proximal-distal axis of the large
      intestine, we analyzed microarray data in 184 normal human specimens using
      univariate and multivariate techniques. We found 219 probe sets that were
      differentially expressed between the proximal and distal colorectal regions and
      115 probe sets that were differentially expressed between the terminal segments,
      i.e., the cecum and rectum. We did not observe any probe sets that were
      statistically different between any two contiguous colorectal segments. The
      dominant expression pattern (65 probe sets) follows a dichotomous expression
      pattern consistent with the midgut-hindgut embryonic origins of the gut while a
      second pattern (50 probe sets) depicts a gradual change in transcript levels from
      the cecum to the rectum. While the dichotomous pattern includes roughly equal
      numbers of probe sets that are elevated proximally and distally, nearly all probe
      sets that show a gradual change demonstrate increasing expression levels moving
      from proximal to distal segments. These patterns describe an expression map of
      individual transcript variation as well as multigene expression patterns along
      the large intestine. This is the first gene expression map of an entire human
      organ.

PMID- 18056784
TI  - Genome-wide gene expression profiling reveals renal genes regulated during
      metabolic acidosis.
AB  - Production and excretion of acids are balanced to maintain systemic acid-base
      homeostasis. During metabolic acidosis (MA) excess acid accumulates and is
      removed from the body, a process achieved, at least in part, by increasing renal
      acid excretion. This acid-secretory process requires the concerted regulation of
      metabolic and transport pathways, which are only partially understood. Chronic MA
      causes also morphological remodeling of the kidney. Therefore, we characterized
      transcriptional changes in mammalian kidney during MA to gain insights into
      adaptive pathways. Total kidney RNA from control and 2- and 7-days NH(4)Cl
      treated mice was subjected to microarray gene profiling. We identified 4,075
      transcripts significantly (P < 0.05) regulated after 2 and/or 7 days of
      treatment. Microarray results were confirmed by qRT-PCR. Analysis of candidate
      genes revealed that a large group of regulated transcripts was represented by
      different solute carrier transporters, genes involved in cell growth,
      proliferation, apoptosis, water homeostasis, and ammoniagenesis. Pathway analysis
      revealed that oxidative phosphorylation was the most affected pathway.
      Interestingly, the majority of acutely regulated genes after 2 days, returned to
      normal values after 7 days suggesting that adaptation had occurred. Besides these
      temporal changes, we detected also differential regulation of selected genes
      (SNAT3, PEPCK, PDG) between early and late proximal tubule. In conclusion, the
      mammalian kidney responds to MA by temporally and spatially altering the
      expression of a large number of genes. Our analysis suggests that many of these
      genes may participate in various processes leading to adaptation and restoration
      of normal systemic acid-base and electrolyte homeostasis.

PMID- 18056785
TI  - Gene expression in mouse brain following chronic hypoxia: role of sarcospan in
      glial cell death.
AB  - Hypoxia is a hallmark of respiratory, neurological, or hematological diseases as
      well as life at high altitude. For example, chronic constant hypoxia (CCH) occurs
      in chronic lung diseases or at high altitude, whereas chronic intermittent
      hypoxia (CIH) occurs in diseases such as sleep apnea or sickle cell disease.
      Despite the fact that such conditions are frequent, the cellular and molecular
      mechanisms underlying the effect of hypoxia, whether constant or intermittent,
      are not well understood. In this study, we first determined the effect of CCH and
      CIH on global gene expression in different regions of mouse brain using
      microarrays and then investigated the biological role of genes of interest. We
      found that: 1) in the cortical region, the expression level of 80 genes was
      significantly altered by CIH (16 up- and 64 downregulated), and this number
      increased to 137 genes following CCH (34 up- and 103 downregulated); 2) a similar
      number of gene alterations was identified in the hippocampal area, and the
      majority of the changes in this region were upregulations; 3) two genes (Sspn and
      Ttc27) were downregulated in both brain regions and following both treatments;
      and 4) RNA interference-mediated knockdown of Sspn increased cell death in
      hypoxia in a cell culture system. We conclude that CIH or CCH induced significant
      and distinguishable alterations in gene expression in cortex and hippocampus and
      that Sspn seems to play a critical role in inducing cell death under hypoxic
      conditions.

PMID- 18056786
TI  - Gene expression changes of prostanoid synthases in endothelial cells and
      prostanoid receptors in vascular smooth muscle cells caused by aging and
      hypertension.
AB  - The present study was designed to assess whether or not changes in genomic
      expression of cyclooxygenases (COX-1, COX-2), endothelial nitric oxide synthase
      (eNOS), and prostanoid synthases in the endothelium and of prostanoid receptors
      in vascular smooth muscle contribute to the occurrence of endothelium-dependent
      contractions during aging and hypertension. Gene expression was quantified by
      real-time PCR using isolated endothelial cells and smooth muscle cells (SMC) from
      the aorta of Wistar-Kyoto and spontaneously hypertensive rats. Genes for all
      known prostanoid synthases and receptors were present in endothelial cells and
      SMC, respectively. Aging caused overexpression of eNOS, COX-1, COX-2, thromboxane
      synthase, hematopoietic-type prostaglandin D synthase, membrane prostaglandin E
      synthase-2, and prostaglandin F synthase in endothelial cells and COX-1 and
      prostaglandin E(2) (EP)(4) receptors in SMC. Hypertension augmented the
      expression of COX-1, prostacyclin synthase, thromboxane synthase, and
      hematopoietic-type prostaglandin D synthase in endothelial cells and
      prostaglandin D(2) (DP), EP(3), and EP(4) receptors in SMC. The increase in
      genomic expression of endothelial COX-1 explains why in aging and hypertension
      the endothelium has greater propensity to release cyclooxygenase-derived
      vasoconstrictive prostanoids. The expression of prostacyclin synthase was by far
      the most abundant, explaining why the majority of the COX-1-derived endoperoxides
      are transformed into prostacyclin, substantiating the role of prostacyclin as an
      endothelium-derived contracting factor. The expression of thromboxane synthase
      was increased in the cells of aging or hypertensive rats, explaining why the
      prostanoid can contribute to endothelium-dependent contractions. It is uncertain
      whether the gene modifications caused by aging and hypertension directly
      contribute to endothelium-dependent contractions or rather to vascular aging and
      the vascular complications of the hypertensive process.

PMID- 18056787
TI  - Leptin increases endothelin type A receptor levels in vascular smooth muscle
      cells.
AB  - Leptin, one of the adipocyte-secreted peptides, is involved in the control of
      appetite and body weight. Several studies have demonstrated that plasma leptin
      levels are elevated in obese subjects and are positively correlated with body
      weight. The arterial endothelin (ET) system plays an important role in the
      regulation of vascular tone, and ET-1 overexpression may be involved in the
      pathogenesis of the hypertension associated with insulin resistance. This study
      was performed to explore the regulatory effects of leptin on ET receptor
      expression and ET binding in A10 vascular smooth muscle cells (VSMCs) by use of
      Northern blotting, immunoblotting, and a (125)I-labeled ET-1 binding assay. The
      effect of leptin on ET receptor-mediated cell proliferation was also tested. The
      results showed that leptin caused a significant increase in [(125)I]-ET-1
      binding, which was time- and dose-dependent. Immunoblotting showed that
      expression of the ET type A receptor (ET(A)R) in leptin (10(-7) M)-treated cells
      was increased by up to 2.3-fold compared with controls. Levels of ET(A)R mRNA
      measured by Northern blotting were also increased by up to 2.2-fold in leptin
      (10(-7) M)-treated cells. Pretreatment with an ERK inhibitor, PD-98059 (2.5 x 10(
      5) M), blocked the leptin-induced increase in (125)I-ET-1 binding. Finally, ET-1
      (10(-7) M)-stimulated cell proliferation was enhanced by leptin (10(-7) M)
      pretreatment, with a maximal increase of twofold compared with controls. In
      conclusion, leptin increases ET(A)R expression in VSMCs in a time- and dose
      dependent manner. This effect is ERK dependent and is associated with increased
      ET-1-stimulated cell proliferation. These findings provide support for roles for
      leptin and the ET system in the pathogenesis of obesity-associated hypertension.

PMID- 18056788
TI  - Intraportally delivered GLP-1, in the presence of hyperglycemia induced via
      peripheral glucose infusion, does not change whole body glucose utilization.
AB  - After a meal, glucagon-like peptide-1 (GLP-1) and glucose levels are
      significantly greater in the hepatic portal vein than in the artery. We have
      previously reported that, in the presence of intraportal glucose delivery, a
      physiological increase of GLP-1 in the hepatic portal vein increases nonhepatic
      glucose uptake via a mechanism independent of changes in pancreatic hormone
      secretion. The aim of the present study was to determine whether intraportal
      glucose delivery is required to observe this effect. Experiments consisted of a
      40-min basal period, followed by a 240-min experimental period, during which
      conscious 42-h fasted dogs received glucose peripherally to maintain arterial
      plasma glucose levels at approximately 160 mg/dl. In addition, either saline (n =
      6) or GLP-1 (1 pmol.kg(-1).min(-1); GLP-1, n = 6) was administered intraportally
      during the experimental period. As in the previous study, the presence of GLP-1
      did not alter pancreatic hormone levels; however, in the present study,
      intraportal GLP-1 infusion did not result in an increase in whole body glucose
      utilization. This is despite the fact that arterial and hepatic portal vein GLP-1
      levels were maintained at the same level as the previous study. Therefore, a
      physiological elevation of GLP-1 in the hepatic portal vein does not increase
      whole body glucose uptake when hyperglycemia is induced by peripheral glucose
      infusion. This indicates that a physiological increase in GLP-1 augments glucose
      utilization only when GLP-1 and glucose gradients conditions mimic the
      postprandial state.

PMID- 18056790
TI  - Diabetes models by screen for hyperglycemia in phenotype-driven ENU mouse
      mutagenesis projects.
AB  - More than 150 million people suffer from diabetes mellitus worldwide, and this
      number is expected to rise substantially within the next decades. Despite its
      high prevalence, the pathogenesis of diabetes mellitus is not completely
      understood. Therefore, appropriate experimental models are essential tools to
      gain more insight into the genetics and pathogenesis of the disease. Here, we
      describe the current efforts to establish novel diabetes models derived from
      unbiased, phenotype-driven, large-scale N-ethyl-N-nitrosourea (ENU) mouse
      mutagenesis projects started a decade ago using hyperglycemia as a high
      throughput screen parameter. Mouse lines were established according to their
      hyperglycemia phenotype over several generations, thereby revealing a mutation as
      cause for the aberrant phenotype. Chromosomal assignment of the causative
      mutation and subsequent candidate gene analysis led to the detection of the
      mutations that resulted in novel alleles of genes already known to be involved in
      glucose homeostasis, like glucokinase, insulin 2, and insulin receptor.
      Additional ENU-induced hyperglycemia lines are under genetic analysis.
      Improvements in screen for diabetic animals are implemented to detect more subtle
      phenotypes. Moreover, diet challenge assays are being employed to uncover
      interactions between genetic and environmental factors in the pathogenesis of
      diabetes mellitus. The new mouse mutants recovered in phenotype-driven ENU mouse
      mutagenesis projects complement the available models generated by targeted
      mutagenesis of candidate genes, all together providing the large resource of
      models required for a systematic dissection of the pathogenesis of diabetes
      mellitus.

PMID- 18056789
TI  - Chronic late-gestation hypoglycemia upregulates hepatic PEPCK associated with
      increased PGC1alpha mRNA and phosphorylated CREB in fetal sheep.
AB  - Hepatic glucose production is normally activated at birth but has been observed
      in response to experimental hypoglycemia in fetal sheep. The cellular basis for
      this process remains unknown. We determined the impact of 2 wk of fetal
      hypoglycemia during late gestation on enzymes responsible for hepatic
      gluconeogenesis, focusing on the insulin-signaling pathway, transcription
      factors, and coactivators that regulate gluconeogenesis. Hepatic
      phosphoenolpyruvate carboxykinase and glucose-6-phosphatase mRNA increased 12
      fold and 7-fold, respectively, following chronic hypoglycemia with no change in
      hepatic glycogen. Chronic hypoglycemia decreased fetal plasma insulin with no
      change in glucagon but increased plasma cortisol 3.5-fold. Peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha mRNA and phosphorylation
      of cAMP response element binding protein at Ser(133) were both increased, with no
      change in Akt, forkhead transcription factor FoxO1, hepatocyte nuclear factor
      4alpha, or CCAAT enhancer binding protein-beta. These results demonstrate that
      chronic fetal hypoglycemia triggers signals that can activate gluconeogenesis in
      the fetal liver.

PMID- 18056792
TI  - Effect of short-term intralipid infusion on the immune response during low-dose
      endotoxemia in humans.
AB  - Novel anti-inflammatory effects of insulin have recently been described, and
      insulin therapy to maintain euglycemia suppresses the plasma levels of free fatty
      acids (FFA) and increases the survival of critically ill patients. We aimed to
      explore the effect of short-term high levels of plasma FFA on the inflammatory
      response to a low dose of endotoxin. Fourteen healthy male volunteers underwent
      the following two trials in a randomized crossover design: 1) continuous infusion
      of 20% Intralipid [0.7 ml.kg(-1).h(-1) (1.54 g/kg)] for 11 h, and 2) infusion of
      isotonic saline for 11 h (control). In each trial, heparin was given to activate
      lipoprotein lipase, and an intravenous bolus of endotoxin (0.1 ng/kg) was given
      after 6 h of Intralipid/saline infusion. Blood samples and muscle and fat
      biopsies were obtained before the Intralipid/saline infusion and before as well
      as after infusion of an endotoxin bolus. Plasma levels of FFA, triglycerides, and
      glycerol were markedly increased during the Intralipid infusion. Endotoxin
      exposure induced an increase in plasma levels of TNF-alpha, IL-6, and neutrophils
      and further stimulated gene expression of TNF-alpha and IL-6 in both skeletal
      muscle and adipose tissue. The systemic inflammatory response to endotoxin was
      significantly pronounced during Intralipid infusion. Short-term hyperlipidemia
      enhances the inflammatory response to endotoxin, and skeletal muscle and adipose
      tissue are capable of producing essential inflammatory mediators after endotoxin
      stimulation.

PMID- 18056791
TI  - Leucine-enriched essential amino acid and carbohydrate ingestion following
      resistance exercise enhances mTOR signaling and protein synthesis in human
      muscle.
AB  - We recently showed that resistance exercise and ingestion of essential amino
      acids with carbohydrate (EAA+CHO) can independently stimulate mammalian target of
      rapamycin (mTOR) signaling and muscle protein synthesis in humans. Providing an
      EAA+CHO solution postexercise can further increase muscle protein synthesis.
      Therefore, we hypothesized that enhanced mTOR signaling might be responsible for
      the greater muscle protein synthesis when leucine-enriched EAA+CHOs are ingested
      during postexercise recovery. Sixteen male subjects were randomized to one of two
      groups (control or EAA+CHO). The EAA+CHO group ingested the nutrient solution 1 h
      after resistance exercise. mTOR signaling was assessed by immunoblotting from
      repeated muscle biopsy samples. Mixed muscle fractional synthetic rate (FSR) was
      measured using stable isotope techniques. Muscle protein synthesis and 4E-BP1
      phosphorylation during exercise were significantly reduced (P < 0.05).
      Postexercise FSR was elevated above baseline in both groups at 1 h but was even
      further elevated in the EAA+CHO group at 2 h postexercise (P < 0.05). Increased
      FSR was associated with enhanced phosphorylation of mTOR and S6K1 (P < 0.05). Akt
      phosphorylation was elevated at 1 h and returned to baseline by 2 h in the
      control group, but it remained elevated in the EAA+CHO group (P < 0.05). 4E-BP1
      phosphorylation returned to baseline during recovery in control but became
      elevated when EAA+CHO was ingested (P < 0.05). eEF2 phosphorylation decreased at
      1 and 2 h postexercise to a similar extent in both groups (P < 0.05). Our data
      suggest that enhanced activation of the mTOR signaling pathway is playing a role
      in the greater synthesis of muscle proteins when resistance exercise is followed
      by EAA+CHO ingestion.

PMID- 18056793
TI  - Regulation of Kruppel-like factor 4, 9, and 13 genes and the steroidogenic genes
      LDLR, StAR, and CYP11A in ovarian granulosa cells.
AB  - Kruppel-like factors (KLFs) are important Sp1-like eukaryotic transcriptional
      proteins. The LDLR, StAR, and CYP11A genes exhibit GC-rich Sp1-like sites, which
      have the potential to bind KLFs in multiprotein complexes. We now report that
      KLF4, KLF9, and KLF13 transcripts are expressed in and regulate ovarian cells.
      KLF4 and 13, but not KLF9, mRNA expression was induced and then repressed over
      time (P < 0.001). Combined LH and IGF-I stimulation increased KLF4 mRNA at 2 h (P
      < 0.01), whereas LH decreased KLF13 mRNA at 6 h (P < 0.05), and IGF-I reduced
      KLF13 at 24 h (P < 0.01) compared with untreated control. KLF9 was not regulated
      by either hormone. Transient transfection of KLF4, KLF9, and KLF13 suppressed
      LDLR/luc, StAR/luc, and CYP11A/luc by 80-90% (P < 0.001). Histone-deacetylase
      (HDAC) inhibitors stimulated LDLR/luc five- to sixfold and StAR/luc and
      CYP11A/luc activity twofold (P < 0.001) and partially reversed suppression by all
      three KLFs (P < 0.001). Deletion of the zinc finger domain of KLF13 abrogated
      repression of LDLR/luc. Lentiviral overexpression of the KLF13 gene suppressed
      LDLR mRNA (P < 0.001) and CYP11A mRNA (P = 0.003) but increased StAR mRNA (P =
      0.007). Collectively, these data suggest that KLFs may recruit inhibitory
      complexes containing HDAC corepressors, thereby repressing LDLR and CYP11A
      transcription. Conversely, KLF13 may recruit unknown coactivators or stabilize
      StAR mRNA, thereby explaining enhancement of in situ StAR gene expression. These
      data introduce new potent gonadal transregulators of genes encoding proteins that
      mediate sterol uptake and steroid biosynthesis.

PMID- 18056795
TI  - N-{4-Chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2
      hydroxybenzamide (CPPHA) acts through a novel site as a positive allosteric
      modulator of group 1 metabotropic glutamate receptors.
AB  - Recent studies suggest that a novel positive allosteric modulator (PAM) of the
      metabotropic glutamate receptor (mGluRs), mGluR5, termed 4-nitro-N-(1,3-diphenyl
      1H-pyrazol-5-yl)benzamide (VU-29), potentiates mGluR5 responses by actions at a
      site that is overlapping with the binding site of 2-methyl-6
      (phenylethynyl)pyridine (MPEP), a previously identified negative allosteric
      modulator of this receptor. It is interesting that a structurally distinct PAM, N
      {4-Chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2
      hydroxybenzamide (CPPHA), does not to bind to the MPEP site. We now report that
      CPPHA potentiates mGluR5 responses by a mechanism that is distinct from that of
      VU-29. VU-29- and CPPHA-induced potentiation of mGluR5 responses are blocked by a
      neutral ligand at the MPEP allosteric site termed 5-methyl-2
      (phenylethynyl)pyridine (5MPEP). However, increasing concentrations of 5MPEP
      induce parallel rightward shifts in the VU-29 concentration-response curve,
      whereas 5MPEP inhibits CPPHA potentiation in a noncompetitive manner. Consistent
      with this, a mutation (A809V/mGluR5) that reduces binding of ligands to the MPEP
      site eliminates the effect of VU-29 but has no effect on the response to CPPHA.
      On the other hand, a mutation (F585I/mGluRs) that eliminates the effect of CPPHA
      does not alter the response to VU-29. CPPHA is also a PAM at mGluR1. It is
      interesting that the corresponding mutation of F585I/mGluR5 in mGluR1
      (F599I/mGluR1) eliminates CPPHA's effect without altering the potentiation of a
      known PAM of mGluR1, (S)-2-(4-fluorophenyl)-1-(toluene-4-sulfonyl)pyrrolidine (Ro
      67-7476). Likewise, another mutation (V757L/mGluR1) that abolishes potentiation
      of Ro 67-7476 has no effect on CPPHA. Finally, CPPHA does not displace binding of
      a radioligand for the mGluR1 allosteric antagonist characterized previously.
      Together, these data suggest that CPPHA acts at a novel allosteric site on both
      mGluR1 and -5 to potentiate responses to activation of these receptors.

PMID- 18056794
TI  - Palmitate action to inhibit glycogen synthase and stimulate protein phosphatase
      2A increases with risk factors for type 2 diabetes.
AB  - Recent studies have suggested that abnormal regulation of protein phosphatase 2A
      (PP2A) is associated with Type 2 diabetes in rodent and human tissues. Results
      with cultured mouse myotubes support a mechanism for palmitate activation of
      PP2A, leading to activation of glycogen synthase kinase 3. Phosphorylation and
      inactivation of glycogen synthase by glycogen synthase kinase 3 could be the
      mechanism for long-chain fatty acid inhibition of insulin-mediated carbohydrate
      storage in insulin-resistant subjects. Here, we test the effects of palmitic acid
      on cultured muscle glycogen synthase and PP2A activities. Palmitate inhibition of
      glycogen synthase fractional activity is increased in subjects with high body
      mass index compared with subjects with lower body mass index (r = -0.43, P =
      0.03). Palmitate action on PP2A varies from inhibition in subjects with decreased
      2-h plasma glucose concentration to activation in subjects with increased 2-h
      plasma glucose concentration (r = 0.45, P < 0.03) during oral glucose tolerance
      tests. The results do not show an association between palmitate effects on PP2A
      and glycogen synthase fractional activity. We conclude that subjects at risk for
      Type 2 diabetes have intrinsic differences in palmitate regulation of at least
      two enzymes (PP2A and glycogen synthase), contributing to abnormal insulin
      regulation of glucose metabolism.

PMID- 18056796
TI  - More than "just a joke": the prejudice-releasing function of sexist humor.
AB  - The results of two experiments supported the hypothesis that, for sexist men,
      exposure to sexist humor can promote the behavioral release of prejudice against
      women. Experiment 1 demonstrated that hostile sexism predicted the amount of
      money participants were willing to donate to a women's organization after reading
      sexist jokes but not after reading nonhumorous sexist statements or neutral
      jokes. Experiment 2 showed that hostile sexism predicted the amount of money
      participants cut from the budget of a women's organization relative to four other
      student organizations upon exposure to sexist comedy skits but not neutral comedy
      skits. A perceived local norm of approval of funding cuts for the women's
      organization mediated the relationship between hostile sexism and discrimination
      against the women's organization.

PMID- 18056797
TI  - Microscopic evidence for the domestication and spread of maize.

PMID- 18056798
TI  - Profile of Joachim Frank.

PMID- 18056799
TI  - Genetic drift at expanding frontiers promotes gene segregation.
AB  - Competition between random genetic drift and natural selection play a central
      role in evolution: Whereas nonbeneficial mutations often prevail in small
      populations by chance, mutations that sweep through large populations typically
      confer a selective advantage. Here, however, we observe chance effects during
      range expansions that dramatically alter the gene pool even in large microbial
      populations. Initially well mixed populations of two fluorescently labeled
      strains of Escherichia coli develop well defined, sector-like regions with
      fractal boundaries in expanding colonies. The formation of these regions is
      driven by random fluctuations that originate in a thin band of pioneers at the
      expanding frontier. A comparison of bacterial and yeast colonies (Saccharomyces
      cerevisiae) suggests that this large-scale genetic sectoring is a generic
      phenomenon that may provide a detectable footprint of past range expansions.

PMID- 18056800
TI  - Neural correlates of trust.
AB  - Trust is a critical social process that helps us to cooperate with others and is
      present to some degree in all human interaction. However, the underlying brain
      mechanisms of conditional and unconditional trust in social reciprocal exchange
      are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in
      which two strangers interacted online with one another in a sequential reciprocal
      trust game while their brains were simultaneously scanned. By designing a
      nonanonymous, alternating multiround game, trust became bidirectional, and we
      were able to quantify partnership building and maintenance. Using within- and
      between-brain analyses, an examination of functional brain activity supports the
      hypothesis that the preferential activation of different neuronal systems
      implements these two trust strategies. We show that the paracingulate cortex is
      critically involved in building a trust relationship by inferring another
      person's intentions to predict subsequent behavior. This more recently evolved
      brain region can be differently engaged to interact with more primitive neural
      systems in maintaining conditional and unconditional trust in a partnership.
      Conditional trust selectively activated the ventral tegmental area, a region
      linked to the evaluation of expected and realized reward, whereas unconditional
      trust selectively activated the septal area, a region linked to social attachment
      behavior. The interplay of these neural systems supports reciprocal exchange that
      operates beyond the immediate spheres of kinship, one of the distinguishing
      features of the human species.

PMID- 18056801
TI  - A portrait of copy-number polymorphism in Drosophila melanogaster.
AB  - Thomas Hunt Morgan and colleagues identified variation in gene copy number in
      Drosophila in the 1920s and 1930s and linked such variation to phenotypic
      differences [Bridges CB (1936) Science 83:210]. Yet the extent of variation in
      the number of chromosomes, chromosomal regions, or gene copies, and the
      importance of this variation within species, remain poorly understood. Here, we
      focus on copy-number variation in Drosophila melanogaster. We characterize copy
      number polymorphism (CNP) across genomic regions, and we contrast patterns to
      infer the evolutionary processes acting on this variation. Copy-number variation
      in D. melanogaster is nonrandomly distributed, presumably because of a mutational
      bias produced by tandem repeats or other mechanisms. Comparisons of coding and
      noncoding CNPs, however, reveal a strong effect of purifying selection in the
      removal of structural variation from functionally constrained regions. Most
      patterns of CNP in D. melanogaster suggest that negative selection and mutational
      biases are the primary agents responsible for shaping structural variation.

PMID- 18056803
TI  - Randomized algorithms for the low-rank approximation of matrices.
AB  - We describe two recently proposed randomized algorithms for the construction of
      low-rank approximations to matrices, and demonstrate their application (inter
      alia) to the evaluation of the singular value decompositions of numerically low
      rank matrices. Being probabilistic, the schemes described here have a finite
      probability of failure; in most cases, this probability is rather negligible (10(
      17) is a typical value). In many situations, the new procedures are considerably
      more efficient and reliable than the classical (deterministic) ones; they also
      parallelize naturally. We present several numerical examples to illustrate the
      performance of the schemes.

PMID- 18056802
TI  - Control of mitotic exit by PP2A regulation of Cdc25C and Cdk1.
AB  - Inactivation of maturation-promoting factor [(MPF) Cdk1/Cyclin B] is a key event
      in the exit from mitosis. Although degradation of Cyclin B is important for MPF
      inactivation, recent studies indicate that Cdk1 phosphorylation and inactivation
      occur before Cyclin B degradation and, therefore, also may be important steps in
      the exit from mitosis. Cdk1 activity is controlled by the Cdc25C phosphatase,
      which is turned on at the G(2)/M transition to catalyze Cdk1 activation.
      PP2A:B56delta is a negative regulator of Cdc25C during interphase. We show here
      that PP2A:B56delta also regulates Cdc25C at mitosis. Failure of PP2A:B56delta to
      dephosphorylate Cdc25C at mitosis results in prolonged hyperphosphorylation and
      activation of Cdc25C, causing persistent dephosphorylation and, hence, activation
      of Cdk1. This constitutive activation of Cdc25C and Cdk1 leads to a delayed exit
      from mitosis. Consistent with Cdk1 as a major biological target of B56delta,
      stable knockdown and germ-line mouse KO of B56delta leads to compensatory
      transcriptional up-regulation of Wee1 kinase to oppose the Cdc25C activity and
      permit cell survival. These observations place PP2A:B56delta as a key upstream
      regulator of Cdk1 activity upon exit from mitosis.

PMID- 18056804
TI  - In vitamin B12 deficiency, higher serum folate is associated with increased total
      homocysteine and methylmalonic acid concentrations.
AB  - In a recent study of older participants (age >/=60 years) in the 1999-2002
      National Health and Nutrition Examination Survey (NHANES), we showed that a
      combination of high serum folate and low vitamin B(12) status was associated with
      higher prevalence of cognitive impairment and anemia than other combinations of
      vitamin B(12) and folate status. In the present study, we sought to determine the
      joint influence of serum folate and vitamin B(12) concentrations on two
      functional indicators of vitamin B(12) status, total homocysteine (tHcy) and
      methylmalonic acid (MMA), among adult participants in phase 2 of the NHANES III
      (1991-1994) and the NHANES 1999-2002. Exclusion of subjects who were <20 years
      old, were pregnant, had evidence of kidney or liver dysfunction, or reported a
      history of alcohol abuse or recent anemia therapy left 4,940 NHANES III
      participants and 5,473 NHANES 1999-2002 participants for the study. Multivariate
      analyses controlled for demographic factors, smoking, alcohol use, body mass
      index, self-reported diabetes diagnosis, and serum concentrations of creatinine
      and alanine aminotransferase revealed significant interactions between serum
      folate and serum vitamin B(12) in relation to circulating concentrations of both
      metabolites. In subjects with serum vitamin B(12) >148 pmol/liter (L),
      concentrations of both metabolites decreased significantly as serum folate
      increased. In subjects with lower serum vitamin B(12), however, metabolite
      concentrations increased as serum folate increased starting at approximately 20
      nmol/L. These results suggest a worsening of vitamin B(12)'s enzymatic functions
      as folate status increases in people who are vitamin B(12)-deficient.

PMID- 18056805
TI  - MicroRNA expression signatures accurately discriminate acute lymphoblastic
      leukemia from acute myeloid leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, whereas
      acute myeloid leukemia (AML) is the most common acute leukemia in adults. In
      general, ALL has a better prognosis than AML. To understand the distinct
      mechanisms in leukemogenesis between ALL and AML and to identify markers for
      diagnosis and treatment, we performed a large-scale genome-wide microRNA (miRNA,
      miR) expression profiling assay and identified 27 miRNAs that are differentially
      expressed between ALL and AML. Among them, miR-128a and -128b are significantly
      overexpressed, whereas let-7b and miR-223 are significantly down-regulated in ALL
      compared with AML. They are the most discriminatory miRNAs between ALL and AML.
      Using the expression signatures of a minimum of two of these miRNAs resulted in
      an accuracy rate of >95% in the diagnosis of ALL and AML. The differential
      expression patterns of these four miRNAs were validated further through large
      scale real-time PCR on 98 acute leukemia samples covering most of the common
      cytogenetic subtypes, along with 10 normal control samples. Furthermore, we found
      that overexpression of miR-128 in ALL was at least partly associated with
      promoter hypomethylation and not with an amplification of its genomic locus.
      Taken together, we showed that expression signatures of as few as two miRNAs
      could accurately discriminate ALL from AML, and that epigenetic regulation might
      play an important role in the regulation of expression of miRNAs in acute
      leukemias.

PMID- 18056806
TI  - Monomeric myosin V uses two binding regions for the assembly of stable
      translocation complexes.
AB  - Myosin-motors are conserved from yeast to human and transport a great variety of
      cargoes. Most plus-end directed myosins, which constitute the vast majority of
      all myosin motors, form stable dimers and interact constitutively with their
      cargo complexes. To date, little is known about regulatory mechanisms for cargo
      complex assembly. In this study, we show that the type V myosin Myo4p binds to
      its cargo via two distinct binding regions, the C-terminal tail and a coiled-coil
      domain-containing fragment. Furthermore, we find that Myo4p is strictly monomeric
      at physiologic concentrations. Because type V myosins are thought to require
      dimerization for processive movement, a mechanism must be in place to ensure that
      oligomeric Myo4p is incorporated into cargo-translocation complexes. Indeed, we
      find that artificial dimerization of the Myo4p C-terminal tail promotes
      stabilization of myosin-cargo complexes, suggesting that full-length Myo4p
      dimerizes in the cocomplex as well. We also combined the Myo4p C-terminal tail
      with the coiled-coil region, lever arm, and motor domain from a different myosin
      to form constitutively dimeric motor proteins. This heterologous motor
      successfully translocates its cargo in vivo, suggesting that wild-type Myo4p may
      also function as a dimer during cargo-complex transport.

PMID- 18056807
TI  - A developmental cycle masks output from the circadian oscillator under conditions
      of choline deficiency in Neurospora.
AB  - In Neurospora, metabolic oscillators coexist with the circadian
      transcriptional/translational feedback loop governed by the FRQ (Frequency) and
      WC (White Collar) proteins. One of these, a choline deficiency oscillator (CDO)
      observed in chol-1 mutants grown under choline starvation, drives an
      uncompensated long-period developmental cycle ( approximately 60-120 h). To
      assess possible contributions of this metabolic oscillator to the circadian
      system, molecular and physiological rhythms were followed in liquid culture under
      choline starvation, but these only confirmed that an oscillator with a normal
      circadian period length can run under choline starvation. This finding suggested
      that long-period developmental cycles elicited by nutritional stress could be
      masking output from the circadian system, although a caveat was that the CDO
      sometimes requires several days to become consolidated. To circumvent this and
      observe both oscillators simultaneously, we used an assay using a codon-optimized
      luciferase to follow the circadian oscillator. Under conditions where the long
      period, uncompensated, CDO-driven developmental rhythm was expressed for weeks in
      growth tubes, the luciferase rhythm in the same cultures continued in a typical
      compensated manner with a circadian period length dependent on the allelic state
      of frq. Periodograms revealed no influence of the CDO on the circadian
      oscillator. Instead, the CDO appears as a cryptic metabolic oscillator that can,
      under appropriate conditions, assume control of growth and development, thereby
      masking output from the circadian system. frq-driven luciferase as a reporter of
      the circadian oscillator may in this way provide a means for assessing
      prospective role(s) of metabolic and/or ancillary oscillators within cellular
      circadian systems.

PMID- 18056808
TI  - The modularity of pollination networks.
AB  - In natural communities, species and their interactions are often organized as
      nonrandom networks, showing distinct and repeated complex patterns. A prevalent,
      but poorly explored pattern is ecological modularity, with weakly interlinked
      subsets of species (modules), which, however, internally consist of strongly
      connected species. The importance of modularity has been discussed for a long
      time, but no consensus on its prevalence in ecological networks has yet been
      reached. Progress is hampered by inadequate methods and a lack of large datasets.
      We analyzed 51 pollination networks including almost 10,000 species and 20,000
      links and tested for modularity by using a recently developed simulated annealing
      algorithm. All networks with >150 plant and pollinator species were modular,
      whereas networks with <50 species were never modular. Both module number and size
      increased with species number. Each module includes one or a few species groups
      with convergent trait sets that may be considered as coevolutionary units.
      Species played different roles with respect to modularity. However, only 15% of
      all species were structurally important to their network. They were either hubs
      (i.e., highly linked species within their own module), connectors linking
      different modules, or both. If these key species go extinct, modules and networks
      may break apart and initiate cascades of extinction. Thus, species serving as
      hubs and connectors should receive high conservation priorities.

PMID- 18056809
TI  - A herpesvirus ubiquitin-specific protease is critical for efficient T cell
      lymphoma formation.
AB  - The herpesvirus ubiquitin-specific protease (USP) family, whose founding member
      was discovered as a protease domain embedded in the large tegument protein of
      herpes simplex virus 1 (HSV-1), is conserved across all members of the
      Herpesviridae. Whether this conservation is indicative of an essential function
      of the enzyme in vivo has not yet been established. As reported here, USP
      activity is conserved in Marek's disease virus (MDV), a tumorigenic
      alphaherpesvirus. A single amino acid substitution that abolishes the USP
      activity of the MDV large tegument protein diminishes MDV replication in vivo,
      and severely limits the oncogenic potential of the virus. Expression of the USP
      transcripts in MDV-transformed cell lines further substantiates this hypothesis.
      The herpesvirus USP thus appears to be required not only to maintain a foothold
      in the immunocompetent host, but also to contribute to malignant outgrowths.

PMID- 18056810
TI  - RET signaling does not modulate MPTP toxicity but is required for regeneration of
      dopaminergic axon terminals.
AB  - Activation of the RET (rearranged during transfection) receptor by glial cell
      line-derived neurotrophic factor (GDNF) has been identified as an important
      differentiation and survival factor for dopaminergic neurons of the midbrain in
      preclinical experiments. These encouraging results have led to clinical trials of
      GDNF in patients with Parkinson's disease, which have resulted in conflicting
      findings. To investigate the potential benefit of Ret-dependent signaling on the
      challenged dopaminergic system, we tested the effect of tissue-selective ablation
      of the Ret gene on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity
      in mice, the most widely used animal model for Parkinson's disease. Ablation of
      Ret did not modify the MPTP-induced loss of dopaminergic neurons in the
      substantia nigra pars compacta and the dopaminergic innervation of the striatum
      at 14 days. However, Ret ablation abolished the regeneration of dopaminergic
      fibers and terminals, as well as the partial recovery of striatal dopamine
      concentrations, that was observed in control mice between days 14 and 90 after
      MPTP treatment. We therefore conclude that RET signaling has no influence on the
      survival of dopaminergic neurons in the MPTP model of Parkinson's disease but
      rather facilitates the regeneration of dopaminergic axon terminals.

PMID- 18056813
TI  - Subliminal exposure to national flags affects political thought and behavior.
AB  - Political thought and behavior play an important role in our lives, from ethnic
      tensions in Europe, to the war in Iraq and the Middle Eastern conflict, to
      parliamentary and presidential elections. However, little is known about how the
      individual's political attitudes and decisions are shaped by subtle national cues
      that are so prevalent in our environment. We report a series of experiments that
      show that subliminal exposure to one's national flag influences political
      attitudes, intentions, and decisions, both in laboratory settings and in "real
      life" behavior. Furthermore, this manipulation consistently narrowed the gap
      between those who score high vs. low on a scale of identification with Israeli
      nationalism. The first two experiments examined participants' stance toward the
      Israeli-Palestinian conflict and the Jewish settlers in the West Bank. Experiment
      3 examined voting intentions and actual voting in Israel's recently held general
      elections. The results portray a consistent picture: subtle reminders of one's
      nationality significantly influence political thought and overt political
      behavior.

PMID- 18056811
TI  - Dramatic increase in naive T cell turnover is linked to loss of naive T cells
      from old primates.
AB  - The loss of naive T cells is a hallmark of immune aging. Although thymic
      involution is a primary driver of this naive T cell loss, less is known about the
      contribution of other mechanisms to the depletion of naive T cells in aging
      primates. We examined the role of homeostatic cycling and proliferative expansion
      in different T cell subsets of aging rhesus macaques (RM). BrdU incorporation and
      the expression of the G(1)-M marker Ki-67 were elevated in peripheral naive CD4
      and even more markedly in the naive CD8 T cells of old, but not young adult, RM.
      Proliferating naive cells did not accumulate in old animals. Rather, the relative
      size of the naive CD8 T cell compartment correlated inversely to its
      proliferation rate. Likewise, T cell receptor diversity decreased in individuals
      with elevated naive CD8 T cell proliferation. This apparent contradiction was
      explained by a significant increase in turnover concomitant with the naive pool
      loss. The turnover increased exponentially when the naive CD8 T cell pool
      decreased below 4% of total blood CD8 cells. These results link the shrinking
      naive T cell pool with a dramatic increase in homeostatic turnover, which has the
      potential to exacerbate the progressive exhaustion of the naive pool and
      constrict the T cell repertoire. Thus, homeostatic T cell proliferation exhibits
      temporal antagonistic pleiotropy, being beneficial to T cell maintenance in
      adulthood but detrimental to the long-term T cell maintenance in aging
      individuals.

PMID- 18056814
TI  - The hidden structure of overimitation.
AB  - Young children are surprisingly judicious imitators, but there are also times
      when their reproduction of others' actions appears strikingly illogical. For
      example, children who observe an adult inefficiently operating a novel object
      frequently engage in what we term overimitation, persistently reproducing the
      adult's unnecessary actions. Although children readily overimitate irrelevant
      actions that even chimpanzees ignore, this curious effect has previously
      attracted little interest; it has been assumed that children overimitate not for
      theoretically significant reasons, but rather as a purely social exercise. In
      this paper, however, we challenge this view, presenting evidence that
      overimitation reflects a more fundamental cognitive process. We show that
      children who observe an adult intentionally manipulating a novel object have a
      strong tendency to encode all of the adult's actions as causally meaningful,
      implicitly revising their causal understanding of the object accordingly. This
      automatic causal encoding process allows children to rapidly calibrate their
      causal beliefs about even the most opaque physical systems, but it also carries a
      cost. When some of the adult's purposeful actions are unnecessary-even
      transparently so-children are highly prone to mis-encoding them as causally
      significant. The resulting distortions in children's causal beliefs are the true
      cause of overimitation, a fact that makes the effect remarkably resistant to
      extinction. Despite countervailing task demands, time pressure, and even direct
      warnings, children are frequently unable to avoid reproducing the adult's
      irrelevant actions because they have already incorporated them into their
      representation of the target object's causal structure.

PMID- 18056816
TI  - Psychosocial interventions and successful aging: new paradigms for improving
      outcome for older schizophrenia patients?

PMID- 18056815
TI  - dsAAV type 2-mediated gene transfer of MORS196A-EGFP into spinal cord as a pain
      management paradigm.
AB  - We previously reported that mutations in the mu-opioid receptor (MOR), S196L or
      S196A, rendered MOR responsive to the opioid antagonist naloxone without altering
      the agonist phenotype. Subsequently, a mouse strain carrying the S196A mutation
      exhibited in vivo naloxone antinociceptive activity without the development of
      tolerance. In this study we investigated the possibility of combining the in vivo
      site-directed delivery of MORS196A and systemic naloxone administration as a
      paradigm for pain management. Double-stranded adenoassociated virus type 2
      (dsAAV2) was used to deliver MORS196A-EGFP by injecting the virus into the spinal
      cord (S2/S3) dorsal horn region of ICR mice. MORS196A-EGFP fluorescence
      colocalized with some calcitonin gene-related peptide and neuron-specific protein
      immunoreactivity in the superficial layers of the dorsal horn 1 week after
      injection and lasted for at least 6 months. In mice injected with the mutant
      receptor, morphine induced similar antinociceptive responses and tolerance
      development or precipitated withdrawal symptoms and reward effects, similar to
      those in the control mice (saline injected into the spinal cord). Conversely, in
      the dsAAV2-injected mice, naloxone produced antinociceptive effects at the spinal
      level but not at the supraspinal level, whereas naloxone had no measurable effect
      on the control mice. Furthermore, the chronic administration of naloxone to mice
      injected with dsAAV2-MORS196A-EGFP did not induce tolerance, dependence, or
      reward responses. Thus, our current approach to activate a mutant receptor, but
      not the endogenous receptor, with an opioid antagonist represents an alternative
      to the use of traditional opioid agonists for pain management.

PMID- 18056817
TI  - Depression in older adults with schizophrenia spectrum disorders: prevalence and
      associated factors.
AB  - RATIONALE: Although depression is common in older adults with schizophrenia, it
      has not been well studied. The authors examine those factors that are related to
      depression in a multiracial urban sample of older persons with schizophrenia.
      METHODS: The schizophrenia group consisted of 198 persons aged 55 or older who
      lived in the community and developed schizophrenia before age 45. Persons with
      substantial cognitive impairment were excluded from the study. A community
      comparison group (N = 113) was recruited using randomly selected census tract
      data. The authors adapted George's Social Antecedent Model of Depression, which
      consists of six categories comprising 16 independent variables, and used a
      dichotomous dependent variable based on a Center for Epidemiologic Studies
      Depression Scale cutoff score of > or = 16. RESULTS: The schizophrenia group had
      significantly more persons with clinical depression than the community comparison
      group (32% versus 11%, respectively; chi(2) = 28.23, df = 1, p = 0.001).
      Bivariate analysis revealed that eight of the 16 variables were significantly
      related to clinical depression in the schizophrenia group. In logistic
      regression, six variables retained significance: physical illness (odds ratio
      [OR] = 1.60, 95% confidence interval [CI], 1.17-2.18), quality of life (OR =
      0.84, 95% CI, 0.76-0.93), presence of positive symptoms (OR = 1.12, 95% CI, 1.02
      1.21), proportion of confidants (OR = 0.03, 95% CI, 0.01-0.39), copes by using
      medications (OR = 2.12, 95% CI, 1.08-4.13), and copes with conflicts by keeping
      calm (OR = 1.34, 95% CI, 1.03-1.74). CONCLUSION: Consistent with earlier studies
      of schizophrenia in older persons, the authors found physical health, positive
      symptoms, and several nonclinical variables to be associated with depression.
      Potential points for intervention include strengthening social supports,
      improving physical well-being, more aggressive treatment of positive symptoms,
      and increasing the recognition and treatment of depression.

PMID- 18056818
TI  - Psychotic symptoms and paranoid ideation in a population-based sample of 95-year
      olds.
AB  - OBJECTIVE: To examine the 1-year prevalence of psychotic symptoms and
      schizophrenia in nondemented 95-year-olds, and to examine the relation between
      psychotic symptoms and other psychiatric symptoms, sensory impairments, and
      cognitive functioning. PARTICIPANTS: The representative sample was 95-year-olds
      living in Goteborg, Sweden (N = 338). Individuals with dementia were excluded (N
      = 175), leaving 163 subjects for this study. DESIGN: This was a cross-sectional
      population study, including psychiatric and physical examinations, cognitive
      tests, and interviews with close informants. MEASUREMENTS: Diagnosis of
      schizophrenia, psychotic symptoms, paranoid ideation and dementia according to
      Diagnostic and Statistical Manual of Mental Disorders, Third Revision (DSM-III)
      were measured. Cognitive function was tested with the Mini-Mental State Exam.
      Other psychiatric symptoms were measured by the Comprehensive Psychopathological
      Rating Scale. RESULTS: The one-year prevalence of any psychotic symptom was 7.4%
      (95% confidence interval [CI] 3.8-12.5); including hallucinations 6.7% (95% CI
      3.4-11.8) and delusions 0.6% (95% CI 0.0-3.4). Four (2.4%) individuals fulfilled
      DSM-III-R criteria for schizophrenia. Individuals with psychotic symptoms or
      paranoid ideation did not differ regarding cognitive functioning compared with
      individuals without these symptoms. Individuals with hallucinations and paranoid
      ideation had an increased frequency of previous paranoid personality traits
      compared with individuals without psychotic symptoms and paranoid ideation. No
      individuals with psychotic symptoms had a formal thought disorder, incoherence of
      speech, or flat affect. CONCLUSION: The authors found a high prevalence of
      psychotic symptoms, paranoid ideation, and schizophrenia in the very old. Most of
      the symptoms were elucidated by information from key informants, illustrating the
      importance of including relatives in the evaluation of elderly persons.

PMID- 18056819
TI  - Subsyndromal depressive symptoms in middle-aged and older persons with
      schizophrenia.
AB  - OBJECTIVE: The objectives are to delineate the nature of subsyndromal depressive
      symptoms (SSD) in midlife and older patients with schizophrenia and
      schizoaffective disorder by: 1) describing the relationship of SSD with a number
      of other clinical features; and 2) examining which specific depressive symptoms
      are increased in patients broadly defined as having SSD. METHODS: A total of 204
      participants with schizophrenia or schizoaffective disorder and SSD who entered a
      federally funded intervention study at the University of California San Diego
      (UCSD) and University of Cincinnati were matched with schizophrenic and
      schizoaffective participants from the Geriatric Research Center at UCSD who had
      minimal or no depressive symptoms. The SSD and no depression groups were compared
      on a variety of clinical features including general psychopathology, positive and
      negative symptoms, medical and mental functioning, cognition, movement
      abnormalities, and specific depressive symptomatology. RESULTS: SSD was
      associated with increases in overall psychopathology; positive and negative
      symptoms; severity of general medical conditions; impaired physical and mental
      functioning; possibly more severe akathisia; and more depressive symptoms
      throughout the spectrum of symptom clusters measured by the Hamilton Depression
      Rating Scale, including anxiety and suicidality. CONCLUSIONS: SSD in middle aged
      and older patients with schizophrenia is an important clinical dimension that
      appears to be associated with substantial morbidity and distress. The findings
      suggest that is important for clinicians to look for and assess subsyndromal
      depressive symptoms in patients with chronic schizophrenia.

PMID- 18056820
TI  - Factors affecting quality of life in a multiracial sample of older persons with
      schizophrenia.
AB  - OBJECTIVE: There have been few studies of quality of life (QOL) among older
      persons with schizophrenia. The authors used an adaptation of Lehman's QOL model
      to examine factors that impact QOL in a multiracial urban sample of older persons
      with schizophrenia. METHODS: The schizophrenia group consisted of 198 community
      dwelling persons aged 55 years and older who developed schizophrenia before age
      45 years. A community comparison group (N = 113) was recruited using randomly
      selected block-groups. The QOL model consisted of four variable sets
      (demographic, objective, clinical, and subjective) comprising 19 independent
      variables. The dependent variable was the Quality of Life Index (QLI). RESULTS:
      The schizophrenia group had a significantly lower QLI score than the comparison
      group (21.7 versus 24.2; t = -5.36, df = 362, p = 0.001). Within the
      schizophrenia group, in bivariate analyses, 11 of 19 variables were significantly
      related to QLI. In regression analysis, six variables were significantly
      associated with the QLI: fewer depressive symptoms, more cognitive deficits,
      fewer acute life stressors, fewer medication side effects, lower financial
      strain, and better self-rated health. The model explained 55% of the variance in
      QLI, with the demographic, objective, psychiatric illness, and subjective
      variable sets accounting for 6%, 35%, 9%, and 5% of the variance, respectively.
      With the exception of the demographic set, each of the variable sets added
      significant variance. CONCLUSION: Our data confirmed earlier reports that older
      persons with schizophrenia have lower self-reported quality of life than their
      age-matched peers. Our findings suggest that the factors impacting on QOL are
      potentially ameliorable and therefore provide an opportunity to enhance the well
      being of this population.

PMID- 18056821
TI  - The relationship between suicide ideation and late-life depression.
AB  - OBJECTIVE: To describe the course of suicide ideation (SI) in primary-care based
      late-life depression treatment, identify predictors of SI, characterize the
      dynamic relationship between depression and SI, and test the hypothesis that
      collaborative care decreases the likelihood of reporting SI by decreasing the
      severity of depressive symptoms. METHODS: This was a secondary analysis of a
      randomized controlled trial comparing collaborative care to usual care for late
      life depression. Participants were 1,801 adults age 60 and older from eight
      diverse primary-care systems. Depression was measured using the Hopkins Symptoms
      Checklist (HSCL-20). SI was operationalized using one item from the HSCL-20.
      Predictors of incident SI were identified by a series of univariate analyses
      followed by multiple logistic regression. A mediator analysis was conducted to
      test the hypothesis that the effect of collaborative care on SI can be ascribed
      to the intervention's effect on depressive symptoms. RESULTS: The prevalence of
      SI was 14% (N = 253); the cumulative incidence over 24 months was 21% (385). The
      likelihood that SI emerged after baseline was highly dependent on change in
      depression (odds ratio: 5.38, 95% confidence interval: 3.93-7.36, df = 81, t =
      10.66, p <0.0001). As hypothesized, the effect of collaborative care on SI was
      mediated by the treatment's effect on depression. CONCLUSION: SI is not uncommon
      in depressed older adults being treated in primary care. The likelihood that
      depressed older adults will report SI is strongly determined by the course of
      their depression symptoms. Providers should monitor SI throughout the course of
      depression treatment.

PMID- 18056822
TI  - Diagnostic criteria influence dementia prevalence.
AB  - OBJECTIVE: The objective of this study was to compare the prevalence of dementia
      using different diagnostic systems, and to investigate the influence of the
      different diagnostic components (memory impairment, personality changes,
      definition of other intellectual functions) on the prevalence. METHODS: A general
      population sample of 1,019 elderly living in Gothenburg, Sweden was investigated
      by using the Comprehensive Psychopathological Rating Scale as well as specific
      assessments relevant for dementia diagnoses. Diagnoses were given according to
      the 9th and 10th version of the International Classification of Diseases (ICD-9,
      ICD-10) as well as the 3rd revised and 4th edition of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-III-R, DSM-IV). Further, "historical"
      criteria for dementia were applied as had been used in older studies. RESULTS:
      DSM-IV dementia occurred most frequently (9.6%), followed by dementia according
      to "historical" criteria (7.4%), DSM-III-R (6.3%), ICD-10 (3.1%), and ICD-9
      (1.2%). The kappa values for the agreement between the diagnostic systems were
      between 0.166 and 0.810. The requirement of both long-term and short-term memory
      impairment in DSM-III-R and personality changes in ICD-10 explained most of the
      differences. When these requirements were held constant, DSM-III-R, DSM-IV, ICD
      10 and "historical" criteria identified predominantly the same persons as
      demented (kappa: 0.810-1.000). CONCLUSION: Prevalence of dementia varied widely
      depending on diagnostic classification system used. For DSM-III-R, DSM-IV, ICD
      10, and "historical" criteria, the definitions of personality changes and
      combinations of memory impairment lead to differing prevalence rates, whereas the
      definitions of other intellectual functions have little impact.

PMID- 18056823
TI  - Mental illness and use of home care nationally in the U.S. Department of Veterans
      Affairs.
AB  - OBJECTIVE: To determine whether patients with mental health diagnoses are more
      likely to utilize home-based primary care (HBPC), and to identify characteristics
      associated with HBPC admission among elderly and nonelderly veterans,
      specifically. METHODS: Patients receiving treatment during fiscal year (FY) 2003
      and having no evidence of home care utilization during FY2002 were followed
      through FY2005 using administrative claims data of the Veterans Health
      Administration of the U.S. Department of Veterans Affairs (VA). Participants were
      4,411,677 VA patients with no prior HBPC use. Cox proportional hazard models were
      developed to identify correlates of HBPC use. RESULTS: Of VA patients with no
      prior use of HBPC, 24.2% received a mental health diagnosis, of whom 1.5%
      eventually used HBPC. Two in five new HBPC admissions were diagnosed with mental
      illness. Patients diagnosed with dementia were 66% more likely to be admitted.
      Patients diagnosed with nonschizophrenia psychoses (hazard ratio [HR]: 1.30),
      miscellaneous affective disorders (HR: 1.22), and schizophrenia (HR: 1.21) had
      the next highest probabilities. Risk of admission was highest for > or = 3
      outpatient medical visits (HR: 2.61), followed by any inpatient medical/surgical
      days (HR: 1.79) or outpatient mental health visits (HR: 1.30). Elderly patients
      with any inpatient mental health days were less likely to be admitted; younger
      patients with nursing home use, community residential care, and mental health
      intensive care management were more likely to be admitted. CONCLUSION: Given that
      mental illness is independently associated with the likelihood of admission, it
      is critical that providers develop the skills and resources necessary to meet the
      psychiatric needs of home care recipients.

PMID- 18056824
TI  - Asymptomatic spontaneous cerebral emboli and mood in a cohort of older people: a
      prospective study.
AB  - OBJECTIVE: To examine whether asymptomatic spontaneous cerebral emboli (SCE)
      predicts subsequent depression in older people. METHODS: Prospective cohort study
      with 2.5 years of follow-up including 96 nondepressed older subjects in primary
      care. Presence of SCE was measured at baseline by transcranial Doppler of the
      middle cerebral artery and modeled on depression at follow-up using multiple
      logistic and linear regression analyses. RESULTS: The prevalence of depressive
      disorder according to Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition criteria did not differ significantly between SCE-positive and SCE
      negative subjects (27% versus 12%), while the severity of depressive symptoms did
      (Geriatric Depression Scale: beta = 0.22; Montgomery-Asberg Depression Rating
      Scale: beta = 0.25). These differences disappeared after adjustment for
      cardiovascular risk factors. CONCLUSION: These preliminary findings suggest that
      asymptomatic SCE may be an interceding factor in the development of late-life
      depression, consistent with the vascular depression hypothesis.

PMID- 18056828
TI  - Designation of major mycobacterial interspersed repetitive-unit types within
      Mycobacterium tuberculosis Beijing genotype, an important point.

PMID- 18056829
TI  - New Vitek 2 colorimetric GN Card for identification of gram-negative
      nonfermentative bacilli.

PMID- 18056830
TI  - Is there convincing biological or behavioral evidence linking vitamin D
      deficiency to brain dysfunction?
AB  - Vitamin D insufficiency is common in the United States; the elderly and African
      Americans are at particularly high risk of deficiency. This review, written for a
      broad scientific readership, presents a critical overview of scientific evidence
      relevant to a possible causal relationship between vitamin D deficiency and
      adverse cognitive or behavioral effects. Topics discussed are 1) biological
      functions of vitamin D relevant to cognition and behavior; 2) studies in humans
      and rodents that directly examine effects of vitamin D inadequacy on cognition or
      behavior; and 3) immunomodulatory activity of vitamin D relative to the
      proinflammatory cytokine theory of cognitive/behavioral dysfunction. We conclude
      there is ample biological evidence to suggest an important role for vitamin D in
      brain development and function. However, direct effects of vitamin D inadequacy
      on cognition/behavior in human or rodent systems appear to be subtle, and in our
      opinion, the current experimental evidence base does not yet fully satisfy causal
      criteria. Possible explanations for the apparent inconsistency between results of
      biological and cognitive/behavioral experiments, as well as suggested areas for
      further research are discussed. Despite residual uncertainty, recommendations for
      vitamin D supplementation of at-risk groups, including nursing infants, the
      elderly, and African-Americans appear warranted to ensure adequacy.

PMID- 18056831
TI  - Buspirone for autistic disorder in a woman with an intellectual disability.
AB  - OBJECTIVE: To describe a case of an intellectually disabled patient who was
      diagnosed with autistic disorder (AD) and responded positively to buspirone,
      demonstrated by a reduction in target behaviors of self-injury, property
      destruction, and physical aggression. CASE SUMMARY: A 33-year-old, white,
      nonverbal, profoundly intellectually impaired woman (IQ <20-25), residing in a
      state-run facility, exhibited worsening aggressive behaviors associated with AD.
      These behaviors were characterized by a history of self-injurious behavior (eg,
      slapping and scratching herself); property destruction, including breaking
      windows; and head butting of staff and peers. Additional diagnoses included a
      seizure disorder, hyperprolactinemia, and osteoporosis. At the time of admission,
      her drug regimen included 3 atypical antipsychotic agents: risperidone,
      clozapine, and aripiprazole. Antipsychotic agents have been reported to lower the
      seizure threshold, and elevated prolactin levels have been associated with
      risperidone use. Aripiprazole and clozapine were discontinued on admission, and
      risperidone was discontinued one month later following increased behavioral
      deterioration. Buspirone was considered an appropriate replacement medication, as
      it has not been associated with elevated prolactin levels or a lowered seizure
      threshold, and was initiated at 15 mg/day. Significant reductions in aggression
      were noted following titration to a total daily dose of 90 mg. DISCUSSION:
      Buspirone is approved for treatment of generalized anxiety disorder in adults.
      Dopaminergic agonist/antagonist actions have been reported with use of higher
      doses. These receptor effects have been beneficial for aggressive behaviors in
      the AD population that were exhibited by our patient, but effectiveness for
      aggression in the intellectually disabled population is uncertain. In our
      patient, problematic behaviors associated with AD responded positively to
      buspirone. CONCLUSIONS: The reduction in target aggressive behaviors achieved
      with buspirone therapy allowed other treatment interventions to proceed more
      effectively in our patient. Clinicians may wish to consider use of buspirone in
      patients with AD who do not respond to or have risk factors for use of other
      therapy.

PMID- 18056832
TI  - Accuracy of oral liquid measuring devices: comparison of dosing cup and oral
      dosing syringe.
AB  - BACKGROUND: Previous studies have found that teaspoons are commonly used to
      administer liquid medications to children. The capacity of household teaspoons
      ranges from 1.5 mL to 9 mL, potentially leading to errors in dosing. There are
      few studies evaluating alternative measuring devices. OBJECTIVE: To assess adult
      consumers' previous experience with measuring devices for oral liquids, compare
      the accuracy of an oral syringe with that of a dosing cup, and determine consumer
      perceptions of accuracy and ease of use of an oral syringe and a dosing cup.
      METHODS: Individuals at least 18 years of age were shown a picture of 5 commonly
      used measurement devices and asked their perceptions of and experience with the
      devices. They were then asked to measure a 5 mL (1 teaspoon) dose of Tylenol
      (acetaminophen) suspension, using the EZY Dose oral syringe and the dosing cup
      provided by the manufacturer. An acceptable dose was defined as 5.0 +/- 0.5 mL.
      Following the measurement, participants completed a 5 item survey that assessed
      their perceptions of the accuracy and ease of use of the syringe and dosing cup.
      RESULTS: A total of 96 subjects completed the study. Participants more commonly
      reported use of droppers (68%), dosing cups (67%), and teaspoons (62%) versus
      cylindrical spoons (49%) or oral syringes (49%) for measuring oral liquids. Sixty
      four (66.7%) subjects measured an acceptable dose using the syringe versus 14
      subjects (14.6%) using the cup (p < 0.001). The mean volumes +/- SD measured with
      the syringe and cup were 4.5 +/- 0.7 mL and 6.3 +/- 0.7 mL, respectively (p <
      0.001). After using both devices, the majority of subjects believed that the
      syringe (80%) and cup (71%) would measure an accurate dose. Most (87%)
      participants perceived that the cup was easy to use; 63% believed that the
      syringe was easy to use. CONCLUSIONS: Droppers and dosing cups were the most
      commonly used devices in the home for measuring liquid medications. Subjects were
      more likely to measure an acceptable dose with an oral syringe when compared with
      a dosing cup. However, a large proportion of study participants were unable to
      measure an accurate dose with either device. Community pharmacists should educate
      caregivers on the selection and proper use of measuring devices to improve the
      accuracy of medication administration in the home.

PMID- 18056833
TI  - Efficacy of memantine on behavioral and psychological symptoms related to
      dementia: a systematic meta-analysis.
AB  - BACKGROUND: The behavioral and psychological symptoms related to dementia (BPSD)
      are difficult to manage and are associated with adverse patient outcomes.
      OBJECTIVE: To systematically analyze the data on memantine in the treatment of
      BPSD. METHODS: We searched MEDLINE, EMBASE, Pharm-line, the Cochrane Centre
      Collaboration, www.clinicaltrials.gov, www.controlled-trials.com, and PsycINFO
      (1966-July 2007). We contacted manufacturers and scrutinized the reference
      sections of articles identified in our search for further references, including
      conference proceedings. Two researchers (IM and CF) independently reviewed all
      studies identified by the search strategy. We included 6 randomized, parallel
      group, double-blind studies that rated BPSD with the Neuropsychiatric Inventory
      (NPI) in our meta-analysis. Patients had probable Alzheimer's disease and
      received treatment with memantine for at least one month. Overall efficacy of
      memantine on the NPI was established with a t-test for the average difference
      between means across studies, using a random effects model. RESULTS: Five of the
      6 studies identified had NPI outcome data. In these 5 studies, 868 patients were
      treated with memantine and 882 patients were treated with placebo. Patients on
      memantine improved by 1.99 on the NPI scale (95% Cl -0.08 to -3.91; p = 0.041)
      compared with the placebo group. CONCLUSIONS: Initial data appear to indicate
      that memantine decreases NPI scores and may have a role in managing BPSD.
      However, there are a number of limitations with the current data; the effect size
      was relatively small, and whether memantine produces significant clinical benefit
      is not clear.

PMID- 18056834
TI  - Impaired response to GM-CSF and G-CSF, and enhanced apoptosis in C/EBPbeta
      deficient hematopoietic cells.
AB  - Transcription factors known as CCAAT enhancer binding proteins (C/EBPs) are
      involved in hematopoietic differentiation, including myelopoiesis and
      granulopoiesis. C/EBPbeta-deficient mice develop normally; however, they exhibit
      defective macrophage function, resulting in increased susceptibility to
      infection. Little is known about the role of C/EBPbeta in granulopoiesis;
      therefore, we examined granulopoiesis in C/EBPbeta-deficient mice. Morphology,
      the number of peripheral blood and bone marrow cells, and the expression of genes
      specific for the myeloid lineage were normal in C/EBPbeta-deficient mice.
      Interestingly, the hematopoietic progenitor cells of C/EBPbeta-deficient mice did
      not respond normally to granulocyte/macrophage-colony stimulating factor and
      granulocyte colony stimulating factor. In addition, C/EBPbeta-deficient
      neutrophils displayed enhanced apoptosis compared with wild-type neutrophils. Our
      present results indicate that C/EBPbeta helps regulate survival of neutrophils,
      downstream of the granulocyte colony stimulating factor receptor.

PMID- 18056835
TI  - Local production and activation of complement up-regulates the allostimulatory
      function of dendritic cells through C3a-C3aR interaction.
AB  - Donor cell expression of C3 enhances the alloimmune response and is associated
      with the fate of transplantation. To clarify the mechanism for enhancement of the
      immune response, we have explored the role of C3a receptor (C3aR)-ligand
      interaction on murine bone marrow dendritic cells (DCs). We show that DCs either
      lacked receptor for C3a (a C3 cleavage product) or were treated with C3aR
      antagonist, elicited defective T-cell priming against alloantigen expressed on
      the DCs. This was associated with reduced surface expression of major
      histocompatibility complex (MHC) and costimulatory molecules on the DCs, and with
      defective priming in skin allograft rejection. In addition, DCs lacking factor B
      were unable to generate potent T-cell responses against donor antigen, whereas
      lack of C4 had no detectable effect, suggesting a role for the alternative
      pathway contributing to allostimulation. Furthermore, therapeutic complement
      regulator can down-regulate DC allostimulatory function. These findings suggest
      that the capacity of DCs for allostimulation depends on their ability to express,
      activate, and detect relevant complement components leading to C3aR signaling.
      This mechanism, in addition to underpinning the cell-autonomous action of donor
      C3 on allostimulation, has implications for a wider range of immune responses in
      self-restricted T-cell priming.

PMID- 18056836
TI  - Hematopoiesis and immunity of HOXB4-transduced embryonic stem cell-derived
      hematopoietic progenitor cells.
AB  - The ability of embryonic stem (ES) cells to form cells and tissues from all 3
      germ layers can be exploited to generate cells that can be used to treat
      diseases. In particular, successful generation of hematopoietic cells from ES
      cells could provide safer and less immunogenic cells than bone marrow cells,
      which require severe host preconditioning when transplanted across major
      histocompatibility complex barriers. Here, we exploited the self-renewal
      properties of ectopically expressed HOXB4, a homeobox transcription factor, to
      generate hematopoietic progenitor cells (HPCs) that successfully induce high
      level mixed chimerism and long-term engraftment in recipient mice. The HPCs
      partially restored splenic architecture in Rag2(-/-)gamma(c)(-/-)-immunodeficient
      mice. In addition, HPC-derived newly generated T cells were able to mount a
      peptide-specific response to lymphocytic choriomeningitis virus and specifically
      secreted interleukin-2 and interferon-gamma upon CD3 stimulation. In addition,
      HPC-derived antigen presenting cells in chimeric mice efficiently presented viral
      antigen to wild-type T cells. These results demonstrate for the first time that
      leukocytes derived from ES cells ectopically expressing HOXB4 are immunologically
      functional, opening up new opportunities for the use of ES cell-derived HPCs in
      the treatment of hematologic and immunologic diseases.

PMID- 18056837
TI  - Soluble MD-2 is an acute-phase protein and an opsonin for Gram-negative bacteria.
AB  - Myeloid differentiation factor-2 (MD-2) is a lipopolysaccharide (LPS)-binding
      protein usually coexpressed with and binding to Toll-like receptor 4 (TLR4),
      conferring LPS responsiveness of immune cells. MD-2 is also found as a soluble
      protein. Soluble MD-2 (sMD-2) levels are markedly elevated in plasma from
      patients with severe infections, and in other fluids from inflamed tissues. We
      show that sMD-2 is a type II acute-phase protein. Soluble MD-2 mRNA and protein
      levels are up-regulated in mouse liver after the induction of an acute-phase
      response. It is secreted by human hepatocytic cells and up-regulated by
      interleukin-6. Soluble MD-2 binds to Gram-negative but not Gram-positive
      bacteria, and sMD-2 secreted by hepatocytic cells is an essential cofactor for
      the activation of TLR4-expressing cells by Gram-negative bacteria. Soluble MD-2
      opsonization of Gram-negative bacteria accelerates and enhances phagocytosis,
      principally by polymorphonuclear neutrophils. In summary, our results demonstrate
      that sMD-2 is a newly recognized type II acute-phase reactant, an opsonin for
      Gram-negative bacteria, and a cofactor essential for the activation of TLR4
      expressing cells. This suggests that sMD-2 plays a key role in the host innate
      immune response to Gram-negative infections.

PMID- 18056838
TI  - Regulation of adult erythropoiesis by prolyl hydroxylase domain proteins.
AB  - Polycythemia is often associated with erythropoietin (EPO) overexpression and
      defective oxygen sensing. In normal cells, intracellular oxygen concentrations
      are directly sensed by prolyl hydroxylase domain (PHD)-containing proteins, which
      tag hypoxia-inducible factor (HIF) alpha subunits for polyubiquitination and
      proteasomal degradation by oxygen-dependent prolyl hydroxylation. Here we show
      that different PHD isoforms differentially regulate HIF-alpha stability in the
      adult liver and kidney and suppress Epo expression and erythropoiesis through
      distinct mechanisms. Although Phd1(-/-) or Phd3(-/-) mice had no apparent
      defects, double knockout of Phd1 and Phd3 led to moderate erythrocytosis. HIF
      2alpha, which is known to activate Epo expression, accumulated in the liver. In
      adult mice deficient for PHD2, the prototypic Epo transcriptional activator HIF
      1alpha accumulated in both the kidney and liver. Elevated HIF-1alpha levels were
      associated with dramatically increased concentrations of both Epo mRNA in the
      kidney and Epo protein in the serum, which led to severe erythrocytosis. In
      contrast, heterozygous mutation of Phd2 had no detectable effects on blood
      homeostasis. These findings suggest that PHD1/3 double deficiency leads to
      erythrocytosis partly by activating the hepatic HIF-2alpha/Epo pathway, whereas
      PHD2 deficiency leads to erythrocytosis by activating the renal Epo pathway.

PMID- 18056839
TI  - A2B adenosine receptor dampens hypoxia-induced vascular leak.
AB  - Extracellular adenosine has been implicated in adaptation to hypoxia and previous
      studies demonstrated a central role in vascular responses. Here, we examined the
      contribution of individual adenosine receptors (ARs: A1AR/A2AAR/A2BAR/A3AR) to
      vascular leak induced by hypoxia. Initial profiling studies revealed that siRNA
      mediated repression of the A2BAR selectively increased endothelial leak in
      response to hypoxia in vitro. In parallel, vascular permeability was
      significantly increased in vascular organs of A2BAR(-/-)-mice subjected to
      ambient hypoxia (8% oxygen, 4 hours; eg, lung: 2.1 +/- 0.12-fold increase). By
      contrast, hypoxia-induced vascular leak was not accentuated in A1AR(-/-)-, A2AAR(
      /-)-, or A3AR(-/-)-deficient mice, suggesting a degree of specificity for the
      A2BAR. Further studies in wild type mice revealed that the selective A2BAR
      antagonist PSB1115 resulted in profound increases in hypoxia-associated vascular
      leakage while A2BAR agonist (BAY60-6583 [2-[6-amino-3,5-dicyano-4-[4
      (cyclopropylmethoxy)-. phenyl]pyridin-2-ylsulfanyl]acetamide]) treatment was
      associated with almost complete reversal of hypoxia-induced vascular leakage (eg,
      lung: 2.0 +/- 0.21-fold reduction). Studies in bone marrow chimeric A2BAR mice
      suggested a predominant role of vascular A2BARs in this response, while hypoxia
      associated increases in tissue neutrophils were, at least in part, mediated by
      A2BAR expressing hematopoietic cells. Taken together, these studies provide
      pharmacologic and genetic evidence for vascular A2BAR signaling as central
      control point of hypoxia-associated vascular leak.

PMID- 18056840
TI  - MLD according to the WHO classification in AML has no correlation with age and no
      independent prognostic relevance as analyzed in 1766 patients.
AB  - Between February 1996 and December 2004, the German Leukemia Study Initiative
      registered 1766 consecutive patients for the acute myeloid leukemia (AML) 96
      study, all of whom were diagnosed by central cytomorphology according to the
      French-American-British (FAB) and the new World Health Organization (WHO)
      classification. We focused our analysis on the prognostic impact of multilineage
      dysplasia (MLD) as a new parameter of the WHO classification for AML. We could
      not confirm the WHO statement that MLD occurs most frequently in older
      individuals, but we confirmed that MLD is often associated with an unfavorable
      cytogenetic profile (P < .001). In 1332 individuals receiving intensive AML
      therapy presence of MLD was negatively correlated with complete remission (P =
      .001) in univariate, but not in multivariate, analysis. Multivariate analysis of
      either event-free or overall survival again failed to show an independent
      prognostic significance of MLD besides age, cytogenetics, and, in part, NPM1/FLT3
      ITD mutations. Our data support a reassessment of the WHO classification in the
      light of a more biologic understanding of AML. This study is registered at
      www.ClinicalTrials.gov as #NCT00180115.

PMID- 18056841
TI  - BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia.
AB  - Cancer cells acquire disruptions in normal signal transduction pathways and
      homeostatic mechanisms that would trigger apoptosis in normal cells. These
      abnormalities include genomic instability, oncogene activation, and growth factor
      independent proliferation. Therefore, cancer cells likely require a block in
      apoptosis in order to survive. Overexpression of the antiapoptotic protein BCL-2
      provides a block in apoptosis that is frequently observed in cancer cells. We
      have developed methods for the detection and analysis of BCL-2 dependence and
      here apply them to acute lymphoblastic leukemia (ALL). BH3 profiling, a
      mitochondrial assay that classifies blocks in the intrinsic apoptotic pathway,
      indicated a dependence on BCL-2 of both ALL cell lines and primary samples. This
      dependence predicted that BCL-2 would be complexed with select pro-death BH3
      family proteins, a prediction confirmed by the isolation of BCL-2 complexes with
      BIM. Furthermore, the BH3 profiling and protein analysis predicted that ALL cell
      lines and primary cells would be sensitive to ABT-737 as a single agent. Finally,
      BH3 profiling and protein studies accurately predicted a relative degree of
      sensitivity to BCL-2 antagonism in cell lines. The ALL cells studied exhibit BCL
      2 dependence, supporting clinical trials of BCL-2 antagonists in ALL as single
      agents or combination therapies.

PMID- 18056842
TI  - Inhibition of collagen-induced platelet aggregation by anopheline antiplatelet
      protein, a saliva protein from a malaria vector mosquito.
AB  - During blood feeding, mosquitoes inject saliva containing a mixture of molecules
      that inactivate or inhibit various components of the hemostatic response to the
      bite injury as well as the inflammatory reactions produced by the bite, to
      facilitate the ingestion of blood. However, the molecular functions of the
      individual saliva components remain largely unknown. Here, we describe anopheline
      antiplatelet protein (AAPP) isolated from the saliva of Anopheles stephensi, a
      human malaria vector mosquito. AAPP exhibited a strong and specific inhibitory
      activity toward collagen-induced platelet aggregation. The inhibitory mechanism
      involves direct binding of AAPP to collagen, which blocks platelet adhesion to
      collagen and inhibits the subsequent increase in intracellular Ca(2+)
      concentration ([Ca(2+)]i). The binding of AAPP to collagen effectively blocked
      platelet adhesion via glycoprotein VI (GPVI) and integrin alpha(2)beta(1). Cell
      adhesion assay showed that AAPP inhibited the binding of GPVI to collagen type I
      and III without direct effect on GPVI. Moreover, intravenously administered
      recombinant AAPP strongly inhibited collagen-induced platelet aggregation ex vivo
      in rats. In summary, AAPP is a malaria vector mosquito-derived specific
      antagonist of receptors that mediate the adhesion of platelets to collagen. Our
      study may provide important insights for elucidating the effects of mosquito
      blood feeding against host hemostasis.

PMID- 18056843
TI  - Effective and selective inhibition of chronic myeloid leukemia primitive
      hematopoietic progenitors by the dual Src/Abl kinase inhibitor SKI-606.
AB  - Imatinib mesylate (imatinib) is highly effective in the treatment of chronic
      myeloid leukemia (CML) but is less effective in eliminating CML stem cells. We
      investigated whether SKI-606, a potent Bcr-Abl and Src kinase inhibitor without
      anti-PDGF or c-Kit activity, could effectively target primitive CML progenitors.
      CML and normal progenitors were cultured with SKI-606 or imatinib. SKI-606
      effectively inhibited Bcr-Abl kinase activity in CML CD34(+) cells and inhibited
      Src phosphorylation more potently than imatinib. However, SKI-606 and imatinib
      resulted in similar suppression of CML primitive and committed progenitor
      proliferation and growth in CFC and LTC-IC assays. Exposure to either agent alone
      or in combination resulted in only modest increase in apoptosis. Evaluation of
      downstream signaling pathways indicated that Akt and STAT5 activity was not
      changed, but a delayed increase in MAPK activity was seen at high concentrations
      of SKI-606. SKI-606 inhibited normal progenitor proliferation to a lesser extent
      than imatinib. SKI-606 effectively inhibits Bcr-Abl and Src kinase activity and
      inhibits CML progenitor growth with relatively little effect on normal
      progenitors. However, SKI-606 does not demonstrate increased ability to eliminate
      primitive CML progenitors by apoptosis compared with imatinib, emphasizing the
      need for additional strategies besides Bcr-Abl kinase inhibition for curative
      therapy of CML.

PMID- 18056844
TI  - Shaping the future of research: the NHLBI strategic plan.

PMID- 18056845
TI  - Defective binding of factor XI-N248 to activated human platelets.

PMID- 18056847
TI  - No more transplantation in CML?

PMID- 18056849
TI  - HLA-identical sibling stem-cell transplantation in first-remission AML.

PMID- 18056850
TI  - Polycythemia vera following autologous transplantation for AML: insights on the
      kinetics of JAK2V617F clonal dominance.

PMID- 18056851
TI  - Development of original donor cell leukemia after successful engraftment from a
      second donor.

PMID- 18056852
TI  - Potent graft-versus-leukemia effect in BCR/ABL negative chronic myelogenous
      leukemia.

PMID- 18056853
TI  - Donor CTLA-4 +49 A/G*GG genotype is associated with chronic GVHD after HLA
      identical haematopoietic stem-cell transplantations.

PMID- 18056854
TI  - Nodal metastasis in non-small cell lung cancer: accuracy of 3.0-T MR imaging.
AB  - PURPOSE: To prospectively evaluate the diagnostic accuracy of 3.0-T magnetic
      resonance (MR) imaging in the detection of non-small cell lung cancer nodal
      metastasis, with histopathologic analysis as the reference standard. MATERIALS
      AND METHODS: Institutional review board approval and informed consent were
      obtained. From July 2005 to May 2006, 113 patients (91 men, 22 women; age range,
      34-82 years; mean age, 61 years) with non-small cell lung cancer underwent
      thoracic 3.0-T MR imaging followed by surgery or mediastinoscopy. The lymph node
      to-tumor ratios (LTRs) of signal intensity and nodal morphologic characteristics
      (such as eccentric cortical thickening or obliteration of the fatty hilum) were
      assessed on T2-weighted triple-inversion black-blood fast spin-echo images. Nodal
      short-axis diameter was assessed on T1-weighted three-dimensional fast field-echo
      images. Receiver operating characteristic and multivariate logistic regression
      analyses were used for statistical evaluation. RESULTS: The cutoff value (LTR >
      0.84) proved to be most appropriate (area under the receiver operating
      characteristic curve = 0.735, P < .001) in the detection of a nodal metastasis.
      Of the various parameters examined, morphologic characteristics appeared to be
      the most significant (P < .001) parameters for depicting a malignant node
      (multivariate logistic regression analyses; odds ratio, 7.5). Nodal morphology
      was analyzed, and diagnostic sensitivity, specificity, and accuracy were 53% (39
      of 74 nodal stations), 91% (453 of 496 nodal stations), and 86% (492 of 570 nodal
      stations), respectively. CONCLUSION: Morphologic details of lymph nodes on T2
      weighted triple-inversion black-blood fast spin-echo MR images are significant
      for detection of mediastinal or hilar nodal metastasis at 3.0-T MR imaging.

PMID- 18056855
TI  - MR imaging of the brain 1 year after aneurysmal subarachnoid hemorrhage:
      randomized study comparing surgical with endovascular treatment.
AB  - PURPOSE: To prospectively evaluate, with magnetic resonance (MR) imaging, long
      term outcome of the brain after endovascular versus neurosurgical treatment for
      aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: Institutional
      review board approval and informed consent were obtained. One hundred sixty-eight
      (77 men, 91 women; mean age +/- standard deviation, 51 years +/- 13) patients
      were randomly assigned to surgical versus endovascular treatment of the ruptured
      aneurysm with 138 (67 endovascular, 71 surgical) MR examinations 1 year after
      aSAH. The presence, localization, volumes, and cause of lesions were analyzed
      with chi(2), Mann-Whitney U, and Student t tests. Furthermore, correlation
      between MR-detectable brain parenchymal high-signal intensity (SI) lesions on T2-
      and intermediate-weighted MR images and neuropsychologic outcome was evaluated by
      using Spearman correlation coefficient. RESULTS: Only 44 (31.9%) of 138 patients
      had no lesions associated with aSAH. According to intention to treat, lesions
      were more frequent after surgical rather than endovascular treatment,
      predominating in the frontal (surgical: n = 50, [70.4%] vs endovascular: n = 34
      [50.7%], P = .018) and temporal (n = 34 [47.9%] vs n = 15 [22.4%], P = .002)
      lobes. Only endovascular patients had subtentorial lesions (n = 4 [6.0%], P =
      .037). Ischemic lesions in the parental artery territory were more frequent in
      surgical (n = 33 [46.5%]) than in endovascular (n = 15 [22.4%], P = .003)
      patients, with corresponding mean lesion volumes of 20.9 cm(3) +/- 46.5 versus
      17.6 cm(3) +/- 35.8 (P = .209). Ischemic lesions in remote vascular territories
      were equal in frequency and size. Retraction injuries were common in the surgical
      (n = 40, [56.3%]) treatment group. Ischemic lesion volumes correlated with
      neuropsychologic test scores. CONCLUSION: Parenchymal high-SI lesions on T2- and
      intermediate-weighted MR images are more frequent after early surgical rather
      than endovascular treatment of the ruptured aneurysm, and lesion volumes
      correlate with the neuropsychologic test performance.

PMID- 18056856
TI  - MR imaging of right ventricular function after the Ross procedure for aortic
      valve replacement: initial experience.
AB  - PURPOSE: To prospectively assess right ventricular (RV) function after the Ross
      procedure by using magnetic resonance (MR) imaging. MATERIALS AND METHODS: The
      local ethics committee approved the study and informed consent was obtained from
      all participants prior to enrollment in the study. Seventeen patients (15 male,
      two female; mean age +/- standard deviation, 19 years +/- 3.9; imaging performed
      8.3 years after surgery +/- 3.2) and 17 matched controls (15 male, two female;
      mean age +/- standard deviation, 20 years +/- 3.9) were studied by using MR
      imaging. Standard velocity-encoded and multisection multiphase imaging sequences
      were used to assess homograft valve function, systolic and diastolic RV function,
      and RV mass. The two-tailed Mann-Whitney U test and the Spearman rank correlation
      coefficient were used for statistical analysis. RESULTS: Minor degrees of
      homograft stenosis (peak flow velocity between 1.5 and 3.0 m/sec across the
      homograft valve) were found in 12 of 17 patients but not in controls (P < .001).
      A larger RV mass was present in Ross patients than in controls (17.0 g/m(2) +/-
      4.8 vs 10.9 g/m(2) +/- 5.6, P = .004). In addition, impaired diastolic RV
      function was found, as shown by a decreased mean tricuspid valve early filling
      phase-atrial contraction phase (E/A) peak flow velocity ratio (1.56 +/- 0.75 vs
      2.05 +/- 0.58, P = .03). Peak flow velocity across the homograft valve correlated
      with RV mass (r = 0.38, P = .03) and tricuspid valve E/A peak flow velocity ratio
      (r = 0.39, P = .02). RV systolic function was normal in Ross patients (mean RV
      ejection fraction, 52% +/- 8 vs 51% +/- 5; P = .74). CONCLUSION: RV hypertrophy
      and RV diastolic dysfunction are frequently observed in patients after the Ross
      procedure, even in the absence of overt homograft stenosis. RV systolic function
      is still preserved.

PMID- 18056857
TI  - Radiation dose to organs and tissues from mammography: Monte Carlo and phantom
      study.
AB  - PURPOSE: To prospectively determine the radiation dose to the organs of the body
      during standard bilateral two-view mammography by using Monte Carlo simulations
      and a phantom. MATERIALS AND METHODS: A modified version of the Cristy mathematic
      anthropomorphic phantom was implemented in the Geant4 Monte Carlo tool kit to
      simulate the conditions present in screen-film and digital mammography. The
      breast was simulated with compression in both the craniocaudal and the
      mediolateral oblique views. X-rays were tracked from the source until their
      absorption in the body or in the detector or their exit from the simulation
      limits, with recording of all the intermediate interactions in the body. The
      simulation was performed with x-rays of energy ranging from 6 to 35 keV to obtain
      results for clinically relevant spectra. The ratio of dose to an organ in the
      body per unit glandular dose to the breast, denoted the relative organ dose
      (ROD), was computed. The effect of using a body protective shield was also
      investigated. RESULTS: The organs that received an ROD of 0.10% or higher in at
      least one view and one spectrum were the contralateral breast, ipsilateral eye
      and eye lens, heart, ipsilateral lung, and thymus. Among the organs, the maximum
      ROD was 0.62%. The maximum ROD for the bone surfaces was 2.36% and that for the
      red bone marrow was 0.56%. The highest ROD measured for the uterus or fetus at
      the first trimester was less than 10(-5). CONCLUSION: The radiation dose to all
      tissues other than the breast is extremely low. The dose to the first-trimester
      fetus is minimal.

PMID- 18056858
TI  - Advanced expression vector systems: new weapons for plant research and
      biotechnology.

PMID- 18056859
TI  - The analysis of protein-protein interactions in plants by bimolecular
      fluorescence complementation.

PMID- 18056860
TI  - New gateways to discovery.

PMID- 18056861
TI  - Heterologous expression of viral RNA interference suppressors: RISC management.

PMID- 18056862
TI  - Delivery of multiple transgenes to plant cells.

PMID- 18056863
TI  - Chloroplast vector systems for biotechnology applications.

PMID- 18056864
TI  - Recombinational cloning with plant gateway vectors.

PMID- 18056865
TI  - Current status of binary vectors and superbinary vectors.

PMID- 18056867
TI  - The butyrylcholinesterase knockout mouse as a model for human
      butyrylcholinesterase deficiency.
AB  - Butyrylcholinesterase (BChE) is an important enzyme for metabolism of ester
      drugs. Many humans have partial or complete BChE deficiency due to genetic
      variation. Our goal was to create a mouse model of BChE deficiency to allow
      testing of drug toxicity. For this purpose, we created the BChE knockout mouse by
      gene-targeted deletion of a portion of the BCHE gene (accession number M99492).
      The BChE(-/-) mouse had no BChE activity in plasma, but it had low residual
      butyrylthiocholine hydrolase activity in all other tissues attributed to
      carboxylesterase ES-10. The BChE(-/-) mouse had a normal phenotype except when
      challenged with drugs. Nicotinic receptor function as indicated by response to
      nicotine seemed to be normal in BChE(-/-) mice, but muscarinic receptor function
      as measured by response to oxotremorine and pilocarpine was altered. Heart rate,
      blood pressure, and respiration, measured in a Vevo imager, were similar in
      BChE(+/+) and BChE(-/-) mice. Like BChE(-/-) humans, the BChE(-/-) mouse
      responded to succinylcholine with prolonged respiratory arrest. Bambuterol was
      not toxic to BChE(-/-) mice, suggesting it is safe in BChE(-/-) humans. Challenge
      with 150 mg/kg pilocarpine i.p., a muscarinic agonist, or with 50 mg/kg
      butyrylcholine i.p., induced tonicclonic convulsions and death in BChE(-/-) mice.
      This suggests that butyrylcholine, like pilocarpine, binds to muscarinic
      receptors. In conclusion, the BChE(-/-) mouse is a suitable model for human BChE
      deficiency.

PMID- 18056866
TI  - Toward sequencing cotton (Gossypium) genomes.

PMID- 18056868
TI  - p38alpha-selective mitogen-activated protein kinase inhibitor SD-282 reduces
      inflammation in a subchronic model of tobacco smoke-induced airway inflammation.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary
      inflammation, which is relatively insensitive to inhaled corticosteroids. The
      extent of the pulmonary inflammation in COPD correlates with disease severity,
      and it is thought to play a significant role in disease progression. We have
      evaluated a selective p38alpha-selective mitogen-activated protein kinase (MAPK)
      inhibitor, indole-5-carboxamide (ATP-competitive inhibitor of p38 kinase) (SD
      282), in an 11-day model of tobacco smoke (TS)-induced pulmonary inflammation in
      A/J mice, by using dexamethasone as a reference steroid. Two oral treatment
      paradigms were evaluated in this TS model: prophylactic with daily pretreatment
      before each daily exposure, and therapeutic with daily treatment for 6 days
      commencing after 5 days of smoke exposure. Bronchoalveolar lavage and
      histological evaluation of lung sections taken after exposure to TS revealed an
      inflammatory response composed of increased numbers of macrophages and
      neutrophils and enhanced mucin staining. Phospho-p38 staining in macrophages and
      type II epithelial cells after TS exposure was also observed. Given
      prophylactically or therapeutically, dexamethasone failed to inhibit any of the
      TS-induced inflammatory changes. By contrast, SD-282 inhibited TS-induced
      increases in macrophages and neutrophils. Furthermore, SD 282 reduced TS-induced
      increases in cyclooxygenase-2 and interleukin-6 levels, and phospho-p38
      expression in the lungs. In conclusion, SD-282 markedly reduced TS-induced
      inflammatory responses when given prophylactically or therapeutically whereas
      dexamethasone was ineffective. This is the first evidence that a p38alpha
      selective MAPK inhibitor can exert pulmonary anti-inflammatory activity in a TS
      exposure model when given in a therapeutic mode, establishing the potential of
      p38 MAPK inhibitors as a therapy for COPD.

PMID- 18056869
TI  - Program for the conservation and promotion of hearing among adolescents.
AB  - PURPOSE: We describe a program for the promotion of hearing conservation aimed at
      the adolescent population. The intent of our program is to (a) detect hearing
      disorders early, as well as to establish their relation to psychosocial and
      acoustic factors; (b) devise a follow-up procedure to study relevant variables;
      (c) evaluate the relation between hearing disorders and genetic factors, and (d)
      raise the social awareness of the effects of noise and its consequences. METHOD:
      This program, designed to be carried out over a 7-year period, focuses on
      participants from technical schools in the city of Cordoba, Argentina. Every
      student will be examined at age 14-15 years and will be reexamined at age 17-18.
      There will be a yearly follow-up in those cases in which disorders are detected.
      RESULTS AND CONCLUSIONS: We discuss the organization and planning of this
      program, together with its launching in the first of the selected schools. We
      also describe the findings on the following topics: (a) the hearing data on
      adolescents (age 14-15 years); (b) their recreational habits, personality traits,
      and attitudes; and (c) the sound immision characteristics these individuals are
      exposed to during recreational activities.

PMID- 18056870
TI  - Effectiveness of "Dangerous Decibels," a school-based hearing loss prevention
      program.
AB  - PURPOSE: To evaluate the effectiveness of the "Dangerous Decibels" educational
      program in increasing students' knowledge and positively changing their attitudes
      and intended behaviors related to hearing and hearing loss prevention. METHOD:
      Baseline questionnaires were completed by 478 4th-grade students and 550 7th
      grade students. Approximately half of the students in each grade received a 35
      min interactive classroom presentation on hearing and hearing loss prevention.
      The remaining students served as comparison groups. Students who received the
      curriculum filled out questionnaires immediately after the presentation. All
      students filled out follow-up questionnaires 3 months after baseline. RESULTS:
      Fourth-grade students who participated in the Dangerous Decibels presentation
      exhibited significant improvements in knowledge and attitudes related to hearing
      and hearing loss prevention. These improvements were maintained 3 months after
      the presentation. Seventh-grade students also experienced long-term improvements
      in their knowledge base. However, attitudes and intended behaviors in 7th graders
      returned to baseline levels 3 months postpresentation. CONCLUSION: The Dangerous
      Decibels hearing loss prevention program was effective at producing long-term
      improvements in the knowledge base of 4th- and 7th-grade students. Future studies
      should include components on peer pressure and should incorporate repeated,
      multimodality interventions to increase the likelihood of long-term improvement
      in adolescents.

PMID- 18056871
TI  - Perceived hearing status and attitudes toward noise in young adults.
AB  - PURPOSE: To estimate the prevalence of perceived hearing loss, tinnitus, and
      temporary threshold shift (TTS) in community college students and to see whether
      those students' attitudes toward noise affected their perception of their own
      possible hearing loss, tinnitus, and TTS. METHOD: Young adults (N = 245; age 18
      27) completed 3 questionnaires: the Hearing Symptom Description, Youth Attitude
      to Noise Scale, and Adolescents' Habits and Hearing Protection Use. RESULTS:
      Perceived TTS and pain associated with loud noise were the most common hearing
      related factors, followed by perceived tinnitus and hearing loss. The students'
      attitudes toward noise in their daily environment showed the most negative
      response, whereas attitudes toward noise and concentration indicated a more
      positive, or less harmful, response. Chi-square analysis indicated a significant
      correlation between perceived hearing loss and respondents' overall attitudes
      toward noise exposure. Hearing protection use was limited for all participants,
      with the majority reporting never having used hearing protection. CONCLUSION:
      Approximately 6% of respondents reported perceived hearing loss, and 13.5%
      reported prolonged tinnitus. In general, participants had neutral attitudes
      toward noise. Over 20% of participants reported ear pain, tinnitus, and/or TTS
      after noise exposure at least sometimes. Coincidentally, few participants
      reported consistent use of hearing protection.

PMID- 18056872
TI  - Comparison of audiometric screening criteria for the identification of noise
      induced hearing loss in adolescents.
AB  - PURPOSE: To ascertain whether current pure-tone school hearing screening criteria
      used across the United States are adequate for the early identification of noise
      induced hearing loss (NIHL) in adolescents. METHOD: School-based pure-tone
      hearing screening protocols were collected, reviewed, and consolidated from 46
      state agencies. A retrospective categorical analysis of air-conduction
      audiometric thresholds from a computerized database of 9th-grade (n = 376) and
      12th-grade (n = 265) students from a suburban high school was conducted. The
      database analysis was designed to determine whether each screening protocol would
      identify high-frequency notched audiometric configurations suggestive of NIHL
      when using the noise notch criteria described by A. S. Niskar et al. (2001).
      RESULTS: All of the school-based hearing screening criteria identified
      significantly (p <or= .05) fewer students with a high-frequency notch (HFN) than
      the noise notch protocol regardless of screening decibel level specified. Over
      half of the school-based hearing screening protocols used in the United States
      will identify only 22% of the students with an HFN and consequently would fail to
      detect a potential NIHL. CONCLUSIONS: Currently implemented school-based hearing
      screening guidelines are nonstandardized and inadequate for the early
      identification of NIHL. This denies the majority of students the opportunity to
      receive early intervention and to prevent further progression of NIHL. It is
      necessary to identify, standardize, and implement effective and efficient
      screening or monitoring programs for the early detection and prevention of NIHL
      in adolescents.

PMID- 18056875
TI  - Selection strategies for binaural and monaural cochlear implantation.
AB  - PURPOSE: We propose theoretical guidelines for cochlear implant selection
      criteria in adults and children that emphasize the contribution of each ear to
      the binaural advantage. The guidelines outline options for implanting one ear
      only, implanting one ear plus use of a contralateral hearing aid, and implanting
      both ears. METHOD: Our method for selecting the best cochlear implant or hearing
      aid outcome is derived from the amount of usable hearing of the patient. This
      approach requires the measurement of aided speech perception with each ear
      separately and then bilaterally. Guidelines are based on the following: (a)
      overall level of performance with hearing aids relative to what is expected from
      a cochlear implant, (b) the contributions from each ear, and (c) whether there is
      a binaural advantage. CONCLUSIONS: Our general recommendation is to provide the
      patient with the best opportunity for binaural hearing. Since the guidelines put
      forth in this article are theoretically based, future efforts should be aimed at
      examining the validity of these guidelines.

PMID- 18056876
TI  - Stimulus repetition rate and the reference levels for clicks and short tone
      bursts: a warning to audiologists, researchers, calibration laboratories, and
      equipment manufacturers.
AB  - PURPOSE: To make the audiologic community aware of a technical issue with
      potential for misunderstanding that could affect the design, calibration, and use
      of auditory brainstem response (ABR) systems. METHOD: Two international standards
      published in 2007 relating to the stimuli commonly used in ABR tests were studied
      and the behavior of a commercially available ABR system examined with regard to
      the relationship between stimulus level and repetition rate. RESULTS: There is
      potential for misunderstanding of the need to compensate for the effect of
      stimulus rate on stimulus level. Although rapidly presented stimuli appear louder
      as the rate is increased, it is inappropriate to compensate for this when
      calibrating the stimulus level of ABR systems. CONCLUSIONS: Users of ABR systems
      should, if possible, use the stimulus reference levels now available in an
      international standard rather than establish local values. No adjustment of level
      should be made to account for different stimulus repetition rates. Users of ABR
      systems should check their systems to ensure that no automatic level adjustment
      is made; if necessary, equipment manufacturers should be consulted.

PMID- 18056877
TI  - Incidence of responses at the lower audiometric limits.
AB  - PURPOSE: To put forward a symbol extension, consisting of an upward arrow added
      to current symbols, to denote that a patient continued to respond at the
      audiometric limit (i.e., -10 dB HL). Also, to present survey data to characterize
      the incidence of these responses. METHOD: A retrospective survey of 2,821
      sequential audiometric evaluations was performed. Responses at the audiometric
      limits were counted, along with the stimulus conditions (i.e., transducer,
      frequency, and masking) and the age of the patient. RESULTS: A total of 307
      instances of responses at the lower audiometric limits were seen in 173 of these
      cases (6.13%), with the majority by bone conduction. CONCLUSIONS: The overall
      rate of responses at the audiometric limits was low, as expected. However, these
      responses were primarily seen in the age group from 4 to 15 years, and at least
      one such response occurred in 26% of cases in that age range.

PMID- 18056878
TI  - Applicability of central auditory processing disorder models.
AB  - PURPOSE: Central auditory processing disorder ([C]APD) is a relatively recent
      construct that has given rise to 2 theoretical models: the Buffalo Model and the
      Bellis/Ferre Model. These models describe 4 and 5 (C)APD categories,
      respectively. The present study examines the applicability of these models to
      clinical practice. Neither of these models was based on data from peer-reviewed
      sources. METHOD: This is a retrospective study that reviewed 178 records of
      children diagnosed with (C)APD, of which 48 were retained for analysis. RESULTS:
      More than 80% of the children could be classified into one of the Buffalo Model
      categories, while more than 90% remained unclassified under the Bellis/Ferre
      Model. This discrepancy can be explained by the fact that the classification of
      the Buffalo Model is based primarily on a single central auditory test (Staggered
      Spondaic Word), whereas the Bellis/Ferre Model classification uses a combination
      of auditory test results. CONCLUSION: The 2 models provide a conceptual framework
      for (C)APD, but they must be further refined to be fully applicable in clinical
      settings.

PMID- 18056879
TI  - The association between tinnitus and posttraumatic stress disorder.
AB  - PURPOSE: Posttraumatic stress disorder (PTSD) affects nearly 10% of the
      population, a prevalence comparable with that of tinnitus. Similarities between
      the way PTSD and tinnitus influence auditory behaviors include exaggerated
      startle responses and decreased loudness tolerance. Tinnitus loudness is often
      exacerbated by sounds that trigger PTSD-related anxiety. This report addresses
      physical and psychological relations between PTSD and tinnitus. METHOD: A chart
      review of veterans seen over a 4-year period for tinnitus services was conducted.
      Case history and self-assessments of tinnitus handicap were examined in all
      patients. A review of the literature related to triggers and effects of PTSD was
      conducted to explore potential consequences related to the presence of PTSD in
      the Veterans Affairs Medical Center (VAMC) tinnitus population. RESULTS: Chart
      review confirmed that 34% of the first 300 patients enrolled in the VAMC Tinnitus
      Clinic also carried a diagnosis of PTSD. Patient reports citing tinnitus
      severity, suddenness of tinnitus onset, sound-tolerance problems, and sound
      triggered exacerbation of tinnitus were more common for patients with a PTSD
      diagnosis than patients with tinnitus only. CONCLUSIONS: Several neural
      mechanisms linked to both tinnitus and PTSD affect auditory behaviors.
      Audiologists should be aware that patients with tinnitus and PTSD will require
      test protocols and referrals that address these powerful responses.

PMID- 18056880
TI  - Objective and subjective hearing aid assessment outcomes.
AB  - PURPOSE: To determine whether specific sentence recognition assessments were
      sensitive enough to serve as objective outcome measurements that document
      subjective improvements in speech understanding with hearing aids. METHOD: The
      Revised Speech Perception in Noise test (R-SPIN; R. C. Bilger, J. M. Nuetzel, W.
      M. Rabinowitz, & C. Rzeczkowski, 1984), the Hearing in Noise Test (HINT; M.
      Nilsson, S. D. Soli, & J. A. Sullivan, 1994), and the Quick Speech-in-Noise test
      (QuickSIN; Etymotic Research, 2001; M. C. Killion, P. A. Niquette, G. I.
      Gudmundsen, L. J. Revit, & S. Banerjee, 2004) were administered to 21 hearing aid
      users to determine whether the tests could adequately document improvements in
      speech understanding with hearing aids compared with the research participants'
      self-assessments of their own performance. Comparisons were made between unaided
      and aided performance on these sentence tests and on the Hearing Aid Performance
      Inventory (HAPI; B. E. Walden, M. Demorest, & E. Hepler, 1984). RESULTS: The R
      SPIN, the HINT Quiet threshold, and the QuickSIN signal-to-noise ratio (SNR) loss
      were the most sensitive of the sentence recognition tests to objectively assess
      improvements in speech perception performance with hearing aids. Comparisons
      among the subjective and objective outcome measures documented that HAPI ratings
      improved as performance on the R-SPIN, the HINT Quiet threshold, and the QuickSIN
      SNR loss improved. CONCLUSIONS: Objective documentation of subjective impressions
      is essential for determining the efficacy of treatment outcomes in hearing aid
      fitting. The findings reported here more clearly define the relationship between
      objective and subjective outcome measures in an attempt to better define true
      hearing aid benefit.

PMID- 18056881
TI  - Directional benefit in simulated classroom environments.
AB  - PURPOSE: To examine speech recognition performance and subjective ratings for
      directional and omnidirectional microphone modes across a variety of simulated
      classroom environments. METHOD: Speech recognition was measured in a group of 26
      children age 10-17 years in up to 8 listening environments. RESULTS: Significant
      directional benefit was found when the sound source(s) of interest was in front,
      and directional decrement was measured when the sound source of interest was
      behind the participants. Of considerable interest is that a directional decrement
      was observed in the absence of directional benefit when sources of interest were
      both in front of and behind the participants. In addition, limiting directional
      processing to the low frequencies eliminated both the directional deficit and the
      directional advantage. CONCLUSIONS: Although these data support the use of
      directional hearing aids in some noisy school environments, they also suggest
      that use of the directional mode should be limited to situations in which all
      talkers of interest are located in the front hemisphere. These results highlight
      the importance of appropriate switching between microphone modes in the school
      age population.

PMID- 18056882
TI  - Response method in audiometry.
AB  - PURPOSE: This study compared the speed, false-alarm rate, and participant
      preference of different response methods (raising a hand, pushing a response
      button, and giving an oral response) for measuring pure-tone thresholds. METHOD:
      Thirty female university students with normal hearing participated. Response
      method order was randomly assigned to 6 different groups. Air-conduction
      thresholds were measured twice for each response method for each participant in
      octave intervals between 250 Hz and 8000 Hz. The 2nd threshold measurements were
      performed on a different day but within 2 weeks of the initial measurement.
      RESULTS: A significant difference was found when comparing the amount of time
      necessary to complete the test for each response method. On average, it took
      about 1 min less when using the push-button response than when using hand-raise
      or verbal response methods. There was also a significant participant preference
      for using the response button. No significant difference between response method
      for threshold level and number of false positives was found. CONCLUSION: This
      study supports the use of the response button when measuring auditory thresholds
      for young adults with normal hearing.

PMID- 18056883
TI  - Contribution of high-frequency information to the acceptance of background noise
      in listeners with normal and impaired hearing.
AB  - PURPOSE: To determine whether information beyond 2.0 kHz affected the acceptance
      of background noise in listeners with normal and/or impaired hearing. METHOD:
      Speech stimuli (Arizona Travelogue) and multitalker babble were low-pass filtered
      at cutoff frequencies of 2.0, 4.0, and 6.0 kHz and presented using an adaptive
      paradigm to determine the most comfortable level (MCL) and acceptable noise level
      (ANL) for 4 experimental conditions (unfiltered, 2.0, 4.0, and 6.0 kHz) for each
      listener. RESULTS: MCL for listening to speech in quiet was significantly
      increased when the speech stimuli were low-pass filtered at 2.0 kHz relative to
      the unfiltered and 6.0-kHz conditions. Acceptance of background noise was
      significantly poorer when the speech and noise stimuli were low-pass filtered at
      2.0 kHz relative to the 6.0-kHz condition. Listeners with impaired hearing
      sensitivity had significantly greater MCL values than listeners with normal
      hearing, but ANL values were not significantly affected by the hearing
      sensitivity of the listener. CONCLUSIONS: Information beyond 2.0 kHz
      significantly affected MCL and ANL values in both listeners with normal hearing
      and impaired hearing; however, effects for both the MCL and ANL measurements were
      small and may not be significant clinically.

PMID- 18056884
TI  - Are primary care physicians more likely to record diabetes on death certificates?

PMID- 18056885
TI  - Reevaluating the digital divide: current lack of internet use is not a barrier to
      adoption of novel health information technology.

PMID- 18056886
TI  - Cross-sectional and prospective study of lung function in adults with type 2
      diabetes: the Atherosclerosis Risk in Communities (ARIC) study.
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that diabetes is
      independently associated with reduced lung function, both cross-sectionally and
      longitudinally. RESEARCH DESIGN AND METHODS: We conducted cross-sectional and
      prospective analyses of diabetes status and lung function decline using baseline
      and 3-year follow-up data on 1,100 diabetic and 10,162 nondiabetic middle-aged
      adults from the Atherosclerosis Risk in Communities (ARIC) Study. Forced vital
      capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) were measured at
      baseline and at the 3-year follow-up using standard spirometry. RESULTS: At
      baseline, adults with diabetes had significantly lower predicted FVC (96 vs.
      103%, P < 0.001) and predicted FEV(1) (92 vs. 96%, P < 0.001) than those without
      diabetes. These differences remained significant after adjustment for demographic
      characteristics, adiposity, smoking, physical activity index, education, and ARIC
      field center. Graded, inverse associations were observed between hyperglycemia,
      diabetes severity (i.e., duration of diabetes and types of antidiabetes
      medications), and FVC and FEV(1) (all P(trend) < 0.001). In prospective analyses,
      FVC declined faster in diabetic adults than in their nondiabetic counterparts (64
      vs. 58 ml/year, P = 0.01). Diabetes severity as indicated by intensity of
      antidiabetic treatment also showed graded relationships with the rate of FVC
      decline (P < 0.01). CONCLUSIONS: These data support the notion that the lung is a
      target organ for diabetic injury. Additional research is required to identify
      pathophysiologic mechanisms and to determine clinical significance.

PMID- 18056887
TI  - Short-term effects of an educational program on health-seeking behavior for
      infections in patients with type 2 diabetes: a randomized controlled intervention
      trial in primary care.
AB  - OBJECTIVE: The aim of this study was to assess the short-term effects of an
      educational program on (determinants of) self-reported health-seeking behavior
      for infections of the urinary tract (UTIs) and lower respiratory tract (LRTIs) in
      patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a randomized
      controlled trial, 1,124 patients with type 2 diabetes aged between 44 and 85
      years participated. The intervention consisted of a multifaceted educational
      program with an interactive meeting, a leaflet, a Web site, and a consultation
      with the diabetes care provider. The program focused on the needs of patients,
      apparent from a prior focus group and questionnaire study. The primary outcome
      measure was an indicator of health-seeking behavior for UTIs and LRTIs, defined
      as the proportion of participants with a positive score on at least seven of nine
      determinants, six from the Health Belief Model and the additional three domains
      of knowledge, need for information, and intention. The primary outcome was
      measured with questionnaires at baseline and after 5 months. RESULTS: Complete
      outcome data were available for 468 intervention group patients and 472 control
      group patients. In all, 68% of the intervention group patients attended the
      meeting. At baseline, 28% of the participants from the intervention group had a
      positive score on seven of the nine determinants, compared with 27% from the
      control group. After the educational program, these percentages were 53 and 32%,
      respectively (P < 0.001). CONCLUSIONS: Our educational program positively
      influenced determinants of health-seeking behavior for common infections in
      patients with type 2 diabetes.

PMID- 18056888
TI  - Relationship of A1C to glucose concentrations in children with type 1 diabetes:
      assessments by high-frequency glucose determinations by sensors.
AB  - OBJECTIVE: Despite the standing of A1C as the most validated and widely used
      measure for average glycemic control over time, the relationship between A1C and
      glucose concentrations is not completely understood. The purpose of this Diabetes
      Research in Children Network (DirecNet) study was to use continuous glucose
      monitoring data to examine the relationship between A1C and glucose in type 1
      diabetes. RESEARCH DESIGN AND METHODS: Forty-eight youth enrolled in studies of
      the Navigator continuous glucose monitor were encouraged to wear the Navigator
      sensor at home continuously. A1C was measured at baseline, at 3 months, and at 6
      months. Sensor glucose data were directly transmitted via the Internet, assuring
      that essentially all glucose values were analyzed. RESULTS: Subjects had a median
      of 112 h/week of Navigator data in the first 3 months and 115 h/week in the
      second 3 months. The slope of mean glucose over the previous 3 months versus A1C
      was only 18 mg/dl per 1.0% A1C. Individually, there was substantial variation in
      the relationship between mean glucose and A1C. A1C was not associated with
      glucose lability after controlling for mean glucose. Measures of an individual's
      rate of glycation were moderately correlated at the 3- and 6-month visits.
      CONCLUSIONS: As the chemistry of glycation would predict, we found no evidence to
      contradict the simple hypothesis that A1C directly reflects mean glucose over
      time. There is, however, substantial variability in individual mean glucose
      concentrations for a given A1C. Transforming reliable A1C values into calculated
      mean glucose values would, when applied to an individual, introduce substantial
      error.

PMID- 18056889
TI  - Quantifying the impact of a short-interval interruption of insulin-pump infusion
      sets on glycemic excursions.
AB  - This prospective, open-label study was designed to measure the impact of short
      term infusion-set disconnects on glucose levels. Continuous subcutaneous insulin
      infusion therapy allows for uninterrupted delivery of insulin. Patients
      disconnect their insulin pumps from their infusion sets when showering, swimming,
      exercising, or during intimate moments. Interrupting insulin infusion results in
      cessation of basal insulin delivery. Nineteen subjects with type 1 diabetes were
      studied on two separate in-clinic days. One hour after arriving at the clinic in
      a fasting state, subjects either temporarily disconnected their infusion sets
      from their pumps, interrupting basal insulin infusion for 30 min, or, on a
      separate day, changed their infusion sets. Glucose levels were monitored for an
      additional 4 h on both occasions. Changing infusion sets did not affect short
      term glucose control. However, the 30-min interruption of basal insulin infusion
      resulted in significant glucose elevation; approximately 1 mg/dl for each minute
      basal insulin infusion was interrupted.

PMID- 18056891
TI  - The protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with high
      GAD antibody titer in latent autoimmune diabetes in adults: Non Insulin Requiring
      Autoimmune Diabetes (NIRAD) Study 3.
AB  - OBJECTIVE: We previously demonstrated the presence of two different populations
      among individuals with adult-onset autoimmune diabetes: those having either a
      high titer or a low titer of antibodies to GAD (GADAs). Protein tyrosine
      phosphatase nonreceptor type 22 (PTPN22) has been identified as a new
      susceptibility gene for type 1 diabetes and other autoimmune diseases. The aim of
      the present study was to evaluate whether the phenotypic heterogeneity of adult
      onset autoimmune diabetes based on the GADA titer is associated with the PTPN22
      C1858T polymorphism. RESEARCH DESIGN AND METHODS: Analysis for the C1858T
      polymorphism using the TaqMan assay was performed in 250 subjects with adult
      onset autoimmune diabetes, divided into two subgroups with low (<or=32 arbitrary
      units) or high (>32 arbitrary units) GADA titers and 450 subjects with classic
      type 2 diabetes (from the Non Insulin Requiring Autoimmune Diabetes [NIRAD] Study
      cohort of 5,330 subjects with adult-onset diabetes) and in 558 subjects with
      juvenile-onset type 1 diabetes and 545 normoglycemic subjects. RESULTS: Genotype,
      allele, and phenotype distributions of the PTPN22 C1858T variant revealed similar
      frequencies in autoimmune diabetes with high GADA titer and juvenile-onset type 1
      diabetes. An increase in TT and CT genotypes was observed in individuals with a
      high GADA titer compared with a low GADA titer, those with type 2 diabetes, and
      control subjects (P < 0.002 for all comparisons). The PTPN22 1858T allele and
      phenotype frequencies were increased in high GADA titer compared with a low GADA
      titer, type 2 diabetic, and control subjects (P < 0.001 for all comparisons, odds
      ratio 2.6). CONCLUSIONS: In adult-onset autoimmune diabetes, the PTPN22 1858T
      variant is associated only with a high GADA titer, providing evidence of a
      genetic background to clinical heterogeneity identified by GADA titer.

PMID- 18056890
TI  - Should nonalcoholic fatty liver disease be included in the definition of
      metabolic syndrome? A cross-sectional comparison with Adult Treatment Panel III
      criteria in nonobese nondiabetic subjects.
AB  - OBJECTIVE: The ability of the Adult Treatment Panel III (ATP III) criteria of
      metabolic syndrome to identify insulin-resistant subjects at increased
      cardiovascular risk is suboptimal, especially in the absence of obesity and
      diabetes. Nonalcoholic fatty liver disease (NAFLD) is associated with insulin
      resistance and is emerging as an independent cardiovascular risk factor. We
      compared the strength of the associations of ATP III criteria and of NAFLD to
      insulin resistance, oxidative stress, and endothelial dysfunction in nonobese
      nondiabetic subjects. RESEARCH DESIGN AND METHODS: Homeostasis model assessment
      of insulin resistance (HOMA-IR) >2, oxidative stress (nitrotyrosine), soluble
      adhesion molecules (intracellular adhesion molecule-1, vascular cell adhesion
      molecule-1, and E-selectin), and circulating adipokines (tumor necrosis factor
      alpha, leptin, adiponectin, and resistin) were cross-sectionally correlated to
      ATP III criteria and to NAFLD in 197 unselected nonobese nondiabetic subjects.
      RESULTS: NAFLD more accurately predicted insulin resistance than ATP III
      criteria: sensitivity 73 vs. 38% (P = 0.0001); positive predictive value: 81 vs.
      62% (P = 0.035); negative predictive value 87 vs. 74% (P = 0.012); positive
      likelihood ratio 4.39 vs. 1.64 (P = 0.0001); and negative likelihood ratio 0.14
      vs. 0.35 (P = 0.0001). Adding NAFLD to ATP III criteria significantly improved
      their diagnostic accuracy for insulin resistance. Furthermore, NAFLD
      independently predicted HOMA-IR, nitrotyrosine, and soluble adhesion molecules on
      logistic regression analysis; the presence of NAFLD entailed more severe
      oxidative stress and endothelial dysfunction, independent of adiposity or any
      feature of the metabolic syndrome in insulin-resistant subjects. CONCLUSIONS:
      NAFLD is more tightly associated with insulin resistance and with markers of
      oxidative stress and endothelial dysfunction than with ATP III criteria in
      nonobese nondiabetic subjects and may help identify individuals with increased
      cardiometabolic risk in this population.

PMID- 18056892
TI  - Quantifying the excess risk of type 2 diabetes by body habitus measurements among
      Australian aborigines living in remote areas.
AB  - OBJECTIVE: To quantify the risk for type 2 diabetes by body habitus measurements
      among remote-living Australian Aborigines relative to that measured in the
      general Australian population (as characterized by the Australian Diabetes,
      Obesity and Lifestyle [AusDiab] study). RESEARCH DESIGN AND METHODS:
      Anthropometric measurements and diabetes status were assessed by standard
      procedures among Aborigines (n = 1,456) and Australians aged >or=25 years (n =
      11,247). Age-adjusted odds ratios (ORs) for diabetes among Aborigines relative to
      AusDiab participants were calculated by commonly used categories of body size
      measurements. RESULTS: The OR (95% CI) values for diabetes among normal,
      overweight, and obese (by waist) Aboriginal women relative to AusDiab women were
      2.6 (0.6-11.5), 13.1 (6.7-25.7), and 6.1 (4.6-8.0), respectively, and for
      Aboriginal men relative to AusDiab men, they were 7.6 (4.6-12.5), 7.6 (4.3-13.4),
      and 5.2 (3.4-8.0), respectively. Rates of diabetes were also excessive in
      Aborigines for each standard category of BMI. CONCLUSIONS: Higher rates of
      diabetes, even at normal and lower body habitus measurements, among Aborigines
      suggest that strategies for prevention should expand beyond exclusive focus on
      diet and weight management.

PMID- 18056893
TI  - Diabetes-related complications, glycemic control, and falls in older adults.
AB  - OBJECTIVE: Older adults with type 2 diabetes are more likely to fall, but little
      is known about risk factors for falls in this population. We determined whether
      diabetes-related complications or treatments are associated with risk of falls in
      older diabetic adults. RESEARCH DESIGN AND METHODS: In the Health, Aging, and
      Body Composition cohort of well-functioning older adults, participants reported
      falls in the previous year at annual visits. Odds ratios (ORs) for more frequent
      falls among 446 diabetic participants whose mean age was 73.6 years, with an
      average follow-up of 4.9 years, were estimated with continuation ratio models.
      RESULTS: In the first year, 23[corrected]% reported falling; 22, 26,
      30[corrected], and 31[corrected]% fell in subsequent years. In adjusted models,
      reduced peroneal nerve response amplitude (OR 1.50 -95% CI 1.07-2.12], worst
      quartile versus others); higher cystatin-C, a marker of reduced renal function
      (1.38 [1.11-1.71], for 1 SD increase); poorer contrast sensitivity (1.41 [0.97
      2.04], worst quartile versus others); and low A1C in insulin users (4.36 [1.32
      14.46], A1C <or=6 vs. >8%) were associated with risk of falls. In those using
      oral hypoglycemic medications but not insulin, low A1C was not associated with
      risk of falls (1.29 [0.65-2.54], A1C <or=6 vs. >8%). Adjustment for physical
      performance explained some, but not all, of these associations. CONCLUSIONS: In
      older diabetic adults, reducing diabetes-related complications may prevent falls.
      Achieving lower A1C levels with oral hypoglycemic medications was not associated
      with more frequent falls, but, among those using insulin, A1C <or=6% increased
      risk of falls.

PMID- 18056894
TI  - A 39-year-old man with a skin infection.
AB  - The case of Mr M, a previously healthy 39-year-old man with erythema and swelling
      of his finger, illustrates the issues involved in treating community-acquired
      skin and soft tissue infections since the emergence of methicillin-resistant
      Staphylococcus aureus (MRSA) in the community. Most community-acquired infections
      of the skin and soft tissues are caused by S aureus or Streptococcus pyogenes.
      Until recently, infections due to such organisms in the United States could
      safely be treated with an oral antistaphylococcal penicillin or an oral first
      generation cephalosporin. However, the emergence of methicillin-resistant
      staphylococci as community-acquired pathogens has changed the picture as far as
      empirical therapy is concerned. Not only do community-acquired MRSA bacteria
      cause furunculitis and cellulitis, they have also been involved in a variety of
      more serious and life-threatening infections. Most of these organisms are
      susceptible to trimethoprim-sulfamethoxazole, minocycline, doxycycline, and
      rifampin, and these agents, along with clindamycin, have been used in the therapy
      of such infections, even though no clinical trials have proven their efficacy.
      For more serious, life-threatening infections, linezolid or parenteral agents
      such as vancomycin or daptomycin should be considered.

PMID- 18056895
TI  - The cover. Ernesta (Child With Nurse).

PMID- 18056896
TI  - A piece of my mind. Words.

PMID- 18056897
TI  - New therapies for alcohol dependence open options for office-based treatment.

PMID- 18056898
TI  - Researchers deconstruct metastasis: genetic clues revealed.

PMID- 18056899
TI  - Personalized care may help smokers quit.

PMID- 18056900
TI  - Prison inmates and palliative care.

PMID- 18056901
TI  - YouTube as a source of information on immunization: a content analysis.

PMID- 18056902
TI  - Antibiotics and topical nasal steroid for treatment of acute maxillary sinusitis:
      a randomized controlled trial.
AB  - CONTEXT: Acute sinusitis is a common clinical problem that usually results in a
      prescription for antibiotics but the role of antibiotics is debated. Anti
      inflammatory drugs such as topical steroids may be beneficial but are
      underresearched. OBJECTIVE: To determine the effectiveness of amoxicillin and
      topical budesonide in acute maxillary sinusitis. DESIGN, SETTING, AND PATIENTS: A
      double-blind, randomized, placebo-controlled factorial trial of 240 adults (aged
      > or =16 years) with acute nonrecurrent sinusitis (had > or =2 diagnostic
      criteria: purulent rhinorrhea with unilateral predominance, local pain with
      unilateral predominance, purulent rhinorrhea bilateral, presence of pus in the
      nasal cavity) at 58 family practices (74 family physicians) between November 2001
      and November 2005. Patients were randomized to 1 of 4 treatment groups:
      antibiotic and nasal steroid; placebo antibiotic and nasal steroid; antibiotic
      and placebo nasal steroid; placebo antibiotic and placebo nasal steroid.
      INTERVENTION: A dose of 500 mg of amoxicillin 3 times per day for 7 days and 200
      mug of budesonide in each nostril once per day for 10 days. MAIN OUTCOME
      MEASURES: Proportion clinically cured at day 10 using patient symptom diaries and
      the duration and severity of symptoms. RESULTS: The proportions of patients with
      symptoms lasting 10 or more days were 29 of 100 (29%) for amoxicillin vs 36 of
      107 (33.6%) for no amoxicillin (adjusted odds ratio, 0.99; 95% confidence
      interval, 0.57-1.73). The proportions of patients with symptoms lasting 10 or
      more days were 32 of 102 (31.4%) for topical budesonide vs 33 of 105 (31.4%) for
      no budesonide (adjusted odds ratio, 0.93; 95% confidence interval, 0.54-1.62).
      Secondary analysis suggested that nasal steroids were significantly more
      effective in patients with less severe symptoms at baseline. CONCLUSION: Neither
      an antibiotic nor a topical steroid alone or in combination was effective as a
      treatment for acute sinusitis in the primary care setting. TRIAL REGISTRATION:
      isrctn.org Identifier: ISRCTN60825437.

PMID- 18056903
TI  - Antithrombotic strategies in patients with acute coronary syndromes undergoing
      early invasive management: one-year results from the ACUITY trial.
AB  - CONTEXT: At 30-day follow-up, patients with moderate- and high-risk acute
      coronary syndromes (ACS) undergoing early invasive treatment in the ACUITY trial
      with bivalirudin monotherapy vs heparin plus glycoprotein (GP) IIb/IIIa
      inhibitors had noninferior rates of adverse ischemic events with reduced rates of
      major bleeding. Deferred upstream use of GP IIb/IIIa inhibitors for selective
      administration to patients undergoing percutaneous coronary intervention (PCI)
      resulted in a significant reduction in major bleeding, although a small increase
      in composite ischemia could not be excluded. OBJECTIVE: To determine 1-year
      ischemic outcomes for patients in the ACUITY trial. DESIGN, SETTING, AND
      PATIENTS: A prospective, randomized, open-label trial with 1-year clinical follow
      up at 450 academic and community-based institutions in 17 countries. A total of
      13,819 patients with moderate- and high-risk ACS undergoing invasive treatment
      were enrolled between August 23, 2003, and December 5, 2005. INTERVENTIONS:
      Patients were assigned to heparin plus GP IIb/IIIa inhibitors (n = 4603),
      bivalirudin plus GP IIb/IIIa inhibitors (n = 4604), or bivalirudin monotherapy (n
      = 4612). Of these patients, 4605 were assigned to routine upstream GP IIb/IIIa
      administration and 4602 were deferred to selective GP IIb/IIIa inhibitor
      administration. MAIN OUTCOME MEASURE: Composite ischemia (death, myocardial
      infarction, or unplanned revascularization for ischemia) at 1 year. RESULTS:
      Composite ischemia at 1 year occurred in 15.4% of patients assigned to heparin
      plus GP IIb/IIIa inhibitors and 16.0% assigned to bivalirudin plus GP IIb/IIIa
      inhibitors (compared with heparin plus GP IIb/IIIa inhibitors, HR, 1.05; 95% CI,
      0.95-1.16; P = .35), and 16.2% assigned to bivalirudin monotherapy (HR, 1.06; 95%
      CI, 0.95-1.17; P = .29). Mortality at 1 year occurred in an estimated 3.9% of
      patients assigned to heparin plus GP IIb/IIIa inhibitors, 3.9% assigned to
      bivalirudin plus GP IIb/IIIa inhibitors (HR, 0.99; 95% CI, 0.80-1.22; P = .92),
      and 3.8% assigned to bivalirudin monotherapy (HR, 0.96; 95% CI, 0.77-1.18; P =
      .67). Composite ischemia occurred in 16.3% of patients assigned to deferred use
      compared with 15.2% of patients assigned to upstream administration (HR, 1.08;
      95% CI, 0.97-1.20; P = .15). CONCLUSIONS: At 1 year, no statistically significant
      difference in rates of composite ischemia or mortality among patients with
      moderate- and high-risk ACS undergoing invasive treatment with the 3 therapies
      was found. There was no statistically significant difference in the rates of
      composite ischemia between patients receiving routine upstream administration of
      GP IIb/IIIa inhibitors vs deferring their use for patients undergoing PCI. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00093158.

PMID- 18056904
TI  - Cardiorespiratory fitness and adiposity as mortality predictors in older adults.
AB  - CONTEXT: Although levels of physical activity and aerobic capacity decline with
      age and the prevalence of obesity tends to increase with age, the independent and
      joint associations among fitness, adiposity, and mortality in older adults have
      not been adequately examined. OBJECTIVE: To determine the association among
      cardiorespiratory fitness ("fitness"), adiposity, and mortality in older adults.
      DESIGN, SETTING, AND PATIENTS: Cohort of 2603 adults aged 60 years or older (mean
      age, 64.4 [SD, 4.8] years; 19.8% women) enrolled in the Aerobics Center
      Longitudinal Study who completed a baseline health examination during 1979-2001.
      Fitness was assessed by a maximal exercise test, and adiposity was assessed by
      body mass index (BMI), waist circumference, and percent body fat. Low fitness was
      defined as the lowest fifth of the sex-specific distribution of maximal treadmill
      exercise test duration. The distributions of BMI, waist circumference, and
      percent body fat were grouped for analysis according to clinical guidelines. MAIN
      OUTCOME MEASURE: All-cause mortality through December 31, 2003. RESULTS: There
      were 450 deaths during a mean follow-up of 12 years and 31 236 person-years of
      exposure. Death rates per 1000 person-years, adjusted for age, sex, and
      examination year were 13.9, 13.3, 18.3, and 31.8 across BMI groups of 18.5-24.9,
      25.0-29.9, 30.0-34.9, and > or =35.0, respectively (P = .01 for trend); 13.3 and
      18.2 for normal and high waist circumference (> or =88 cm in women; > or =102 cm
      in men) (P = .004); 13.7 and 14.6 for normal and high percent body fat (> or =30%
      in women; > or =25% in men) (P = .51); and 32.6, 16.6, 12.8, 12.3, and 8.1 across
      incremental fifths of fitness (P < .001 for trend). The association between waist
      circumference and mortality persisted after further adjustment for smoking,
      baseline health status, and BMI (P = .02) but not after additional adjustment for
      fitness (P = .86). Fitness predicted mortality risk after further adjustment for
      smoking, baseline health, and either BMI, waist circumference, or percent body
      fat (P < .001 for trend). CONCLUSIONS: In this study population, fitness was a
      significant mortality predictor in older adults, independent of overall or
      abdominal adiposity. Clinicians should consider the importance of preserving
      functional capacity by recommending regular physical activity for older
      individuals, normal-weight and overweight alike.

PMID- 18056906
TI  - Update: an 81-year-old woman with temporal arteritis.

PMID- 18056905
TI  - Persistence of contradicted claims in the literature.
AB  - CONTEXT: Some research findings based on observational epidemiology are
      contradicted by randomized trials, but may nevertheless still be supported in
      some scientific circles. OBJECTIVES: To evaluate the change over time in the
      content of citations for 2 highly cited epidemiological studies that proposed
      major cardiovascular benefits associated with vitamin E in 1993; and to
      understand how these benefits continued being defended in the literature, despite
      strong contradicting evidence from large randomized clinical trials (RCTs). To
      examine the generalizability of these findings, we also examined the extent of
      persistence of supporting citations for the highly cited and contradicted
      protective effects of beta-carotene on cancer and of estrogen on Alzheimer
      disease. DATA SOURCES: For vitamin E, we sampled articles published in 1997,
      2001, and 2005 (before, early, and late after publication of refuting evidence)
      that referenced the highly cited epidemiological studies and separately sampled
      articles published in 2005 and referencing the major contradicting RCT (HOPE
      trial). We also sampled articles published in 2006 that referenced highly cited
      articles proposing benefits associated with beta-carotene for cancer (published
      in 1981 and contradicted long ago by RCTs in 1994-1996) and estrogen for
      Alzheimer disease (published in 1996 and contradicted recently by RCTs in 2004).
      DATA EXTRACTION: The stance of the citing articles was rated as favorable,
      equivocal, and unfavorable to the intervention. We also recorded the range of
      counterarguments raised to defend effectiveness against contradicting evidence.
      RESULTS: For the 2 vitamin E epidemiological studies, even in 2005, 50% of citing
      articles remained favorable. A favorable stance was independently less likely in
      more recent articles, specifically in articles that also cited the HOPE trial
      (odds ratio for 2001, 0.05 [95% confidence interval, 0.01-0.19; P < .001] and the
      odds ratio for 2005, 0.06 [95% confidence interval, 0.02-0.24; P < .001], as
      compared with 1997), and in general/internal medicine vs specialty journals.
      Among articles citing the HOPE trial in 2005, 41.4% were unfavorable. In 2006,
      62.5% of articles referencing the highly cited article that had proposed beta
      carotene and 61.7% of those referencing the highly cited article on estrogen
      effectiveness were still favorable; 100% and 96%, respectively, of the citations
      appeared in specialty journals; and citations were significantly less favorable
      (P = .001 and P = .009, respectively) when the major contradicting trials were
      also mentioned. Counterarguments defending vitamin E or estrogen included diverse
      selection and information biases and genuine differences across studies in
      participants, interventions, cointerventions, and outcomes. Favorable citations
      to beta-carotene, long after evidence contradicted its effectiveness, did not
      consider the contradicting evidence. CONCLUSION: Claims from highly cited
      observational studies persist and continue to be supported in the medical
      literature despite strong contradictory evidence from randomized trials.

PMID- 18056907
TI  - The "tobacco wars"--global litigation strategies.

PMID- 18056908
TI  - Natural and manmade disasters and mental health.

PMID- 18056909
TI  - Acute sinusitis--to treat or not to treat?

PMID- 18056911
TI  - JAMA patient page. Acute sinusitis.

PMID- 18056913
TI  - Genomic maintenance: the p53 poly(ADP-ribosyl)ation connection.
AB  - The integrity of the genome in higher eukaryotes, as well as the modulation of
      its complex structure and functions, is exquisitely regulated. This genomic
      regulation occurs as a function of time in a very sophisticated and elaborate
      biological process called cell cycle progression, resulting in cell division, and
      is also controlled by a highly coordinated and intricate network of molecular
      signaling pathways, which in turn orchestrate very specific macromolecular
      interactions among nuclear proteins and DNA at the biochemical level. Among the
      latter, a prominent enzymatic cycle that is involved in maintaining the integrity
      of mammalian chromosomes is covalent protein-poly[adenosine diphosphate (ADP)
      ribosyl]ation. The importance of this posttranslational modification is
      illustrated by the close cooperation between two "guardian angels" of the genome,
      one constitutive and one inducible protein, namely poly(ADP-ribose) polymerase-1
      (PARP-1) and p53, and the integration of these pivotal signaling processes with
      genomic maintenance.

PMID- 18056914
TI  - Nuclear localization of growth hormone receptor: another age of discovery for
      cytokine action?
AB  - The conventional view of cytokine signaling is that receptors transmit
      information to the nucleus without leaving the plasma membrane. However,
      accumulating data suggest that some membrane receptors may signal by dissociating
      from the plasma membrane and translocating to the nucleus, where they direct the
      transcriptional machinery. One example is the growth hormone receptor (GHR),
      which has been observed in the nuclei of various normal and neoplastic tissues.
      Waters and colleagues now present new mechanistic data describing how GHR might
      localize to the nucleus and influence gene transcription. These findings may have
      implications for the way we think about cytokine signaling.

PMID- 18056915
TI  - Variation of circulating tumor cell levels during treatment of metastatic breast
      cancer: prognostic and therapeutic implications.
AB  - BACKGROUND: This study aimed to evaluate the prognostic significance of
      circulating tumor cells (CTCs) detection in advanced breast cancer patients.
      PATIENTS AND METHODS: We tested 80 patients for CTC levels before starting a new
      treatment and after 4, 8 weeks, at the first clinical evaluation and every 2
      months thereafter. CTCs were detected using the CellSearch System. RESULTS: Forty
      nine patients had >or=5 CTCs at baseline. At the multivariate analysis, baseline
      number of CTCs was significantly associated with progression-free survival
      [hazard ratio (HR) 2.5; 95% confidence interval (CI) 1.2-5.4]. The risk of
      progression for patients with CTCs >or=5 at last available blood draw was five
      times the risk of patients with 0-4 CTCs at the same time point (HR 5.3; 95% CI
      2.8-10.4). Patients with rising or persistent >or=5 CTCs at last available blood
      draw showed a statistically significant higher risk of progression with respect
      to patients with <5 CTCs at both blood draws (HR 6.4; 95% CI 2.8-14.6).
      CONCLUSION: CTCs basal value is a predictive indicator of prognosis and changes
      in CTC levels during therapy may indicate a clinical response. Testing CTC levels
      during targeted treatments might substitute other measurement parameters for
      response evaluation.

PMID- 18056916
TI  - Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial
      role for microcirculation.
AB  - Arterial hypertension (HT) has been reported in all studies involving
      bevacizumab, an antiangiogenic agent designed to target vascular endothelial
      growth factor (VEGF). The mechanism underlying bevacizumab-related HT is not yet
      clearly understood. As far as endothelial dysfunction and microvascular
      rarefaction are hallmarks in all forms of HT, we tested the hypothesis that anti
      VEGF therapy could alter the microcirculation in nontumor tissues and, thus,
      result in an increase in blood pressure (BP). We used intravital video microscopy
      to measure dermal capillary densities in the dorsum of the fingers. Microvascular
      endothelial function was assessed by laser Doppler flowmetry combined with
      iontophoresis of pilocarpine (acetylcholine analogue). All measurements were
      carried out in 18 patients before and after a 6-month treatment with bevacizumab
      (mean cumulative dose: 3.16 +/- 0.90 g). Mean BP was increased after 6 months of
      therapy compared with baseline, from 129 +/- 13/75 +/- 7 mmHg to 145 +/- 17/82 +/
      7 mmHg for systolic BP and diastolic BP, respectively (P < 0.0001). Compared
      with the baseline, mean dermal capillary density at 6 months was significantly
      lower (75 +/- 12 versus 83 +/- 13/mm(2); P < 0.0001), as well as pilocarpine
      induced vasodilation (P < 0.05). Thus, bevacizumab treatment resulted in
      endothelial dysfunction and capillary rarefaction; both changes are closely
      associated and could be responsible for the rise in BP observed in most patients.

PMID- 18056917
TI  - Weight change and cancer risk in a cohort of more than 65,000 adults in Austria.
AB  - BACKGROUND: To investigate relations between weight loss or weight gain and the
      incidence of cancer. PATIENTS AND METHODS: Weight change was assessed in a
      population-based cohort of >65 000 Austrian adults (28 711 men and 36 938 women)
      for a period of 7 years, after which participants were followed for incident
      cancers over 8 years on average. Incident cancers (other than nonmelanoma skin
      cancers) were ascertained by a population-based cancer registry (n = 3128). Cox
      proportional hazards models were used to estimate hazard rate ratios (HRs)
      stratified by age and adjusted for smoking, occupational group, blood glucose and
      body mass index at baseline. RESULTS: In both men and women, neither weight loss
      nor weight gain was clearly associated with the incidence of all cancers
      combined. Weight loss (>0.10 kg/m(2)/year) was inversely associated with colon
      cancer in men [HR 0.50; 95% confidence interval (CI) 0.29-0.87], while high
      weight gain (> or =0.50 kg/m(2)/year) was inversely associated with prostate
      cancer (HR 0.43; 95% CI 0.24-0.76). Among women, high weight gain was positively
      associated with ovarian cancer (HR 2.48; 95% CI 1.05-5.85). CONCLUSION: These
      findings indicate that recent weight change may influence the incidence of
      several types of cancer.

PMID- 18056918
TI  - Low potency of Chlamydophila LPS to activate human mononuclear cells due to its
      reduced affinities for CD14 and LPS-binding protein.
AB  - Chlamydiaceae are small obligate intracellular parasites and classified as Gram
      negative bacteria. Among Chlamydiaceae-derived components, LPS is known as an
      immunomodulator and possesses a unique lipid A structure with longer but fewer
      acyl chains. In this study, to elucidate the Chlamydiaceae-induced immune
      responses, we evaluated the actions of Chlamydophila psittaci LPS as a
      Chlamydiaceae LPS on human PBMCs and compared with those of Escherichia coli LPS.
      Similar to E. coli LPS, C. psittaci LPS bound to monocytes and induced the pro
      inflammatory cytokine production in an LPS-binding protein (LBP)-dependent
      manner. However, C. psittaci LPS was much less potent than E. coli LPS in both
      the LPS binding and cytokine production. Interestingly, although the binding of
      C. psittaci LPS was mediated by CD14, Toll-like receptor 4 (TLR4) and CD11b, CD14
      and TLR4 but not CD11b were involved in the cytokine production. Of note, ELISA
      based binding assays revealed that C. psittaci LPS directly bound to LBP and
      CD14; however, the affinities were much less than those of E. coli LPS. Together,
      these observations possibly suggest that Chlamydiaceae LPS has low binding
      affinities for LPS recognition molecules such as CD14 and LBP and exhibit weak
      biological activities against host immune cells including monocytes, thereby
      contributing to the chronic (persistent) inflammatory reactions during infection.

PMID- 18056919
TI  - Involvement of CC chemokines in gammadelta T lymphocyte trafficking during
      allergic inflammation: the role of CCL2/CCR2 pathway.
AB  - In the present study, we show that the intra-thoracic injection of ovalbumin
      (OVA, 12.5 microg per cavity) into C57BL/10 mice induced a significant increase
      in gammadelta T lymphocyte numbers in the pleural cavity, blood and thoracic
      lymph node of challenged mice. Such increase was significant within 12 h, peaked
      within 48 h and returned to basal counts within 120 h. Levels of CC chemokine
      ligand (CCL)-2/monocyte chemotactic protein-1, CCL5/regulated upon activation,
      normal T cell expressed and secreted, CCL3/macrophage inflammatory protein-1
      alpha and CCL25/thymus-expressed chemokine were above control values in pleural
      washes recovered 24 h after OVA challenge (OPW) and were likely produced by
      pleural macrophages and mesothelial cells. Antigenic challenge also induced an up
      regulation in CC chemokine receptor (CCR)-2, CCR5 and CCR9 on gammadelta T cells
      from pleural cavities, blood and lymph nodes, suggesting that cells found in mice
      pleural cavity migrate from secondary lymphoid organs into the inflammatory site
      via blood stream. The in vitro neutralization of CCL2 (but not of CCL3, CCL5 or
      CCL25) abrogated OPW-induced gammadelta T lymphocyte transmigration. Confirming
      such results, the in vivo administration of alpha-CCL2 mAb inhibited gammadelta T
      lymphocyte accumulation in the pleural cavity of challenged mice, whereas the
      blockade of CCL3, CCL5 or CCL25 showed no effect on gammadelta T cell
      mobilization. In addition, OVA challenge failed to induce gammadelta T lymphocyte
      accumulation in the pleural cavity of C57BL/6 CCR2 knockout mice, which also
      showed decreased numbers of these cells in blood and lymph nodes when compared
      with wild-type mice. Overall, such results demonstrate that CCR2/CCL2 pathway is
      crucial for gammadelta T lymphocyte mobilization during the allergic response.

PMID- 18056920
TI  - Evidence for positive selection on Drosophila melanogaster seminal fluid protease
      homologs.
AB  - Proteins present in the seminal fluid of Drosophila melanogaster (accessory gland
      proteins Acps) contribute to female postmating behavioral changes, sperm storage,
      sperm competition, and immunity. Consequently, male-female coevolution and host
      pathogen interactions are thought to underlie the rapid, adaptive evolution that
      characterizes several Acp-encoding genes. We propose that seminal fluid proteases
      are likely targets of selection due to their demonstrated or potential roles in
      between-sex interactions and immune processes. We use within- and between-species
      sequence data for 5 predicted protease-encoding Acp loci to test this hypothesis.
      Our polymorphism-based analyses find evidence for positive selection at 2 genes,
      both of which encode predicted serine protease homologs. One of these genes,
      CG6069, also shows evidence for consistent selection on a subset of codons over a
      deeper evolutionary time scale. The second gene, CG9997, was previously shown to
      be essential for normal sperm usage, suggesting that sexual selection may
      underlie its history of adaptation.

PMID- 18056921
TI  - Proteomics analysis of host cells infected with infectious bursal disease virus.
AB  - The effect of infectious bursal disease virus (IBDV) infection on cellular
      protein expression is essential for viral pathogenesis. To characterize the
      cellular response to IBDV infection, the differential proteomes of chicken embryo
      fibroblasts, with and without IBDV infection, were analyzed at different time
      points with two-dimensional gel electrophoresis (2-DE) followed by MALDI-TOF/TOF
      identification. Comparative analysis of multiple 2-DE gels revealed that the
      majority of protein expression changes appeared at 48 and 96 h after IBDV
      infection. Mass spectrometry identified 51 altered cellular proteins, including
      13 up-regulated proteins and 38 down-regulated proteins 12-96 h after infection.
      Notably 2-DE analysis revealed that IBDV infection induced the increased
      expression of polyubiquitin, apolipoprotein A-I, heat shock 27-kDa protein 1,
      actins, tubulins, eukaryotic translation initiation factor 4A isoform 2, acidic
      ribosomal phosphoprotein, and ribosomal protein SA isoform 2. In addition, IBDV
      infection considerably suppressed those cellular proteins involved in ubiquitin
      mediated protein degradation, energy metabolism, intermediate filaments, host
      translational apparatus, and signal transduction. Moreover 38 corresponding genes
      of the differentially expressed proteins were quantitated by real time RT-PCR to
      examine the transcriptional profiles between infected and uninfected chicken
      embryo fibroblasts. Western blot further confirmed the inhibition of Rho protein
      GDP dissociation inhibitor expression and the induction of polyubiquitin during
      IBDV infection. Subcellular distribution analysis of the cytoskeletal proteins
      vimentin and beta-tubulin clearly demonstrated that IBDV infection induced the
      disruption of the vimentin network and microtubules late in IBDV infection. Thus,
      this work effectively provides useful dynamic protein-related information to
      facilitate further investigation of the underlying mechanism of IBDV infection
      and pathogenesis.

PMID- 18056922
TI  - High levels of multiple paternity in Littorina saxatilis: hedging the bets?
AB  - The mating system of a species can have great effects on its genetic structure
      and evolution. We studied the extent of multiple paternity in a gastropod with
      internal fertilization, the intertidal snail Littorina saxatilis. Paternal
      genotype reconstruction based on microsatellite markers was performed on the
      offspring of wild, naturally fertilized females from 2 populations. The numbers
      of males contributing to the offspring per female were among the highest detected
      in invertebrates so far, with the exception of social insects. No reproductive
      skew in favor of males that were genetically more distant from the females was
      detected, and the pattern of fertilization appeared random. The result fits a
      hypothesis of indiscriminate mating, with genetic bet hedging as the most likely
      explanation. Bet hedging may have evolved as a form of inbreeding avoidance, if
      the snails are not able to recognize relatives. However, nutritional benefits
      from sperm or sexual conflict with males are additional possibilities that remain
      to be assessed in this species. Whatever the causes, such high levels of multiple
      paternity are remarkable and are likely to have a large impact on population
      structure and dynamics in a species in which migration between populations is
      spurious.

PMID- 18056923
TI  - Associations of serum sex hormone binding globulin (SHBG) levels with SHBG gene
      polymorphisms in the CARDIA Male Hormone Study.
AB  - In the sex hormone binding globulin (SHBG) gene, a pentanucleotide-repeat
      polymorphism [(TAAAA)(n)] and a single nucleotide polymorphism (D327N) have been
      associated with circulating SHBG concentrations in women. Only one study, limited
      to Scandinavians, has examined these associations in men. Using data from the
      Coronary Artery Risk Development in Young Adults (CARDIA) Male Hormone Study, the
      authors assessed associations of SHBG polymorphisms with serum SHBG levels in 511
      Black men and 698 White men who had SHBG measured in multiple serum samples
      collected over an 8-year period from 1987 to 1996 and were aged 20-34 years at
      the time of the first SHBG measurement. Multivariable repeated-measures analyses
      were used to assess associations of (TAAAA)(n) and D327N polymorphisms with SHBG
      concentrations. Results showed statistically significant differences in mean SHBG
      concentrations for White men with genotypes of (TAAAA) 6/6 (35.1 nmol/liter), 6/x
      (30.8 nmol/liter), and x/x (29.6 nmol/liter), where x represents a repeat length
      greater than 6 (p = 0.001). For Black men, the pattern of association was
      similar, albeit not statistically significant (p = 0.35). There was no relation
      between D327N genotype and SHBG levels. These results suggest that the (TAAAA)(n)
      repeat length in the SHBG gene, but not the D327N variant, might contribute to
      the interindividual variability in serum SHBG levels.

PMID- 18056924
TI  - Life-course origins of social inequalities in metabolic risk in the population of
      a developing country.
AB  - In countries that have been industrialized for a long time, but not always
      elsewhere, low socioeconomic position (SEP) is associated with ischemic heart
      disease in men. The authors hypothesized that socioeconomic development could,
      via pubertal sex steroids, promote an atherogenic lipid profile and body shape in
      men but not in women. Therefore, they examined the associations of SEP with
      ischemic heart disease risk in a developing-country population. The authors used
      multivariable regression to examine the associations of SEP with the metabolic
      syndrome and its components in 9,746 Chinese adults aged >/=50 years from the
      Guangzhou Biobank Cohort Study, phase 2, recruited in 2005-2006. After adjustment
      for age, smoking, alcohol use, and physical activity, high SEP at each of three
      life stages, proxied by parental possesions in childhood, education, and longest
      held-occupation, was inversely associated with the metabolic syndrome in women
      but not in men. Higher SEP in men was associated with lower pulse pressure and
      fasting plasma glucose level but also with greater waist circumference and a
      lower high density lipoprotein cholesterol level. With socioeconomic development,
      diet-related hormonal changes at puberty may outweigh the usual protective effect
      of social advantage in men, with corresponding implications for boys currently
      undergoing the nutrition transition in the developing world.

PMID- 18056925
TI  - Tobacco smoking, smoking cessation, and cumulative risk of upper aerodigestive
      tract cancers.
AB  - Upper aerodigestive tract cancers are strongly related to smoking, and their
      incidence is substantially lower in former smokers than in continuing smokers. To
      estimate the effect of smoking cessation on the cumulative incidence of these
      cancers by age 75 years (in the absence of competing causes of death), the
      authors combined odds ratios for males from a network of Italian hospital-based
      case-control studies (1984-2000) with 1993-1997 incidence data for Italian men.
      The studies included 961 cases with oral/pharyngeal cancer, 618 cases with
      esophageal cancer, and 613 cases with laryngeal cancer, plus 3,781 controls. For
      all upper aerodigestive tract cancers, the cumulative risks by 75 years of age
      were 6.3% for men who continued to smoke any type of tobacco, 3.1% and 1.2% for
      men who stopped smoking at around 50 and 30 years of age, respectively, and 0.8%
      among lifelong nonsmokers. Corresponding figures were 3.3%, 1.4%, 0.5%, and 0.2%
      for oral/pharyngeal cancer; 1.0%, 0.5%, 0.4%, and 0.2% for esophageal cancer; and
      2.1%, 1.1%, 0.2%, and 0.2% for laryngeal cancer. In this Italian population, men
      who stopped smoking before age 50 years avoided more than half of the excess risk
      of upper aerodigestive tract cancer as men who did not, and men who stopped
      smoking before age 30 years avoided more than 90% of the risk.

PMID- 18056926
TI  - The trans-10, cis-12 isomer of conjugated linoleic acid decreases adiponectin
      assembly by PPARgamma-dependent and PPARgamma-independent mechanisms.
AB  - The adipocyte-derived secretory protein adiponectin functions as an insulin
      sensitizing agent. In plasma, adiponectin exists as low, medium, and high
      molecular weight oligomers. Treatment with trans-10, cis-12 conjugated linoleic
      acid (t-10, c-12 CLA) reduces levels of adiponectin as well as triglyceride (TG)
      in mice and adipocyte cell culture models. The aim of this study was to determine
      whether the effects of t-10, c-12 CLA on adiponectin and TG are mediated through
      modulation of the transcription factor peroxisome proliferator-activated receptor
      gamma (PPARgamma). 3T3-L1 cells were treated either during or after
      differentiation into adipocytes with 100 microM t-10, c-12 CLA with or without 10
      microM troglitazone, a PPARgamma agonist, or 1 microM GW9662, a PPARgamma
      antagonist, and adiponectin and TG levels were analyzed. Treatment with t-10, c
      12 CLA reduced TG as well as cellular and secreted adiponectin levels and
      impaired the assembly of adiponectin oligomers. These changes were accompanied by
      decreases in PPARgamma mass. Troglitazone was able to reverse the t-10, c-12 CLA
      mediated decrease in TG levels and restore the assembly of adiponectin oligomers
      but was unable to restore adiponectin synthesis. Conversely, treatment with
      GW9662 decreased TG mass and impaired adiponectin oligomer assembly but did not
      decrease total adiponectin mass. In a reporter assay, t-10, c-12 CLA appeared to
      be a partial PPARgamma agonist and prevented the stimulation of reporter activity
      by troglitazone. Therefore, the t-10, c-12 CLA isomer appears to alter adipocyte
      adiponectin metabolism through PPARgamma-dependent and PPARgamma-independent
      mechanisms.

PMID- 18056927
TI  - New strategies in controlling drug resistance in chronic myeloid leukemia.
AB  - PURPOSE: Imatinib has been quite effective in maintaining patients with CML in
      the chronic phase (CP); however, some patients develop imatinib resistance. This
      review addresses the mechanisms underlying imatinib resistance and the strategies
      currently being used to overcome that resistance. SUMMARY: Chronic myeloid
      leukemia (CML) is a stem cell cancer caused by BCR-ABL. Imatinib, a BCR-ABL
      inhibitor, has significantly decreased CML mortality by stopping disease
      progression in CP. This success has been tempered by the appearance of imatinib
      resistant clones. These clones allow CML to progress to advanced stages of
      disease where the prognosis is poor. Mechanisms of imatinib resistance include
      plasma protein binding, drug efflux, mutation of BCR-ABL, gene amplification of
      BCR-ABL, and activation of BCR-ABL independent proliferative pathways. The first
      four of these mechanisms could potentially be addressed by increasing the
      imatinib dose and recent clinical trials have shown this to be the case.
      Pharmacokinetic analysis demonstrated that patients with low imatinib plasma
      concentrations fared more poorly then patients with high plasma concentrations.
      Doubling the standard dose of 400 mg per day increased patient responses while
      decreasing the time to response. Toxicity was also increased resulting in
      approximately 50% of patients decreasing the dose. The strategy of waiting to see
      who failed imatinib at 400 mg per day and then increasing the dose of that
      subpopulation was unsuccessful. The interpretation of these data is that it is
      beneficial to treat CML as aggressively as possible as early as possible.
      Dasatinib is the second BCR-ABL inhibitor to become available. It binds with a
      350-fold greater affinity to BCR-ABL and shows efficacy against a number of
      imatinib-resistant mutations. Dasatinib also inhibits SRC kinase, which may play
      a role in both maintaining BCR-ABL activity and in BCR-ABL independent signaling
      pathways. Clinical trials with dasatinib have had favorable results and are
      comparable with high-dose imatinib. Imatinib also compares favorably with stem
      cell transplant (SCT). Economic analysis shows imatinib and dasatinib therapies,
      while quite expensive, are on par with dialysis in terms of cost of quality
      adjusted life years. CONCLUSION: A better understanding of imatinib resistance
      mechanisms has resulted in the development of useful strategies both to predict
      responders and nonresponders and to minimize imatinib resistance and prolong the
      life of the patient.

PMID- 18056928
TI  - Chronic myeloid leukemia. Introduction.

PMID- 18056929
TI  - Leukemia. Q&A highlights.

PMID- 18056931
TI  - Chronic myeloid leukemia in 2007.
AB  - PURPOSE: Chronic myeloid leukemia (CML), a hematopoietic stem cell cancer
      representing 15-20% of adult leukemias, is discussed. Epidemiology, staging
      biology, and monitoring techniques are reviewed. SUMMARY: CML is a
      myeloproliferative disorder that affects all lineages of hematopoiesis. Final
      confirmation of CML comes with detection of the Philadelphia Chromosome (Ph) or
      BCR-ABL transcripts. The disease presents in one of three phases: chronic phase,
      accelerated phase, or blast crisis. Progression from chronic phase to accelerated
      phase usually involves the accumulation of additional cytogenetic aberrations and
      the arising of resistance to therapy. Although at one point mortality associated
      with CML was high, new kinase inhibitor therapies have markedly extended the life
      span of these patients. These inhibitors were derived through the initial
      observation of the association of the Ph with CML and the eventual identification
      of the BCR-ABL oncogene which arises from this translocation. Analysis of the
      mechanism by which BCR-ABL transforms cells identified this protein as a tyrosine
      kinase and led to the targeting of this activity. The majority of patients
      present in chronic phase, which is where these kinase inhibitors have their
      greatest efficacy. Monitoring of disease progression is of critical importance as
      the prognosis drops significantly for patients with advanced disease. Blood
      counts, cytogenetics, and polymerase chain reaction (PCR) are currently used to
      assess disease. Blood counts are inexpensive but lack sensitivity. Cytogenetic
      karyotyping while requiring specialized training provides evidence of clonal
      evolution. Quantitative PCR is capable of tremendous sensitivity making it well
      suited for assessing response to therapy and the early detection of therapy
      failures. CONCLUSION: Our understanding of BCR-ABL has allowed the development of
      therapies, which may keep patients with CML in chronic phase indefinitely. This
      has created a situation in which patient monitoring is essential for detecting
      changes in the status of CML. The tests described here provide a comprehensive
      assessment of disease status allowing for effective patient management.

PMID- 18056932
TI  - Targeted chronic myeloid leukemia therapy: Seeking a cure.
AB  - PURPOSE: This article focuses on imatinib, how it has altered CML therapy,
      clinical trials that are the basis for its efficacy, and adverse effects
      associated with its current clinical use. SUMMARY: Maintaining patients with CML
      in chronic phase (CP) yields the prospect of improved long-term survival. As
      recently as 1993, CML was limited to treatment with standard cytoreductive
      therapies. These therapies provide temporary disease control but do not alter
      progression to advanced disease with a median survival ranging 45 to 55 months
      from diagnosis. In the 1990s, immunologically based therapy with interferon alpha
      (IFNalpha) therapy was shown to be superior to cytoreductive therapies with a
      median survival of 60 to 90 months. Allogeneic hematopoietic stem cell transplant
      (HSCT) has offered curative potential for patients with CML; however, the median
      age of diagnosis of 55 years, the lack of suitable donors, and the morbidity of
      the procedure precludes widespread applicability of this treatment. Imatinib, the
      first approved tyrosine kinase inhibitor, functions by blocking the ATP binding
      site on the BCR-ABL kinase. It was first shown to be efficacious in patients who
      failed IFNalpha and then tested as a front line therapy (the International
      Randomized Study of Interferon [IRIS] trial). The five year follow up on the IRIS
      trial found that the responses were durable with progression free survival
      estimated at 93%. Imatinib has been found to have a lower rate of hematologic
      response and shorter duration of response in patients with advanced disease.
      Currently patients in blast crisis (BC) have the option to undergo a number of
      induction chemotherapies, such as etoposide, cytarabine, carboplatin (VAC) with
      the hope of temporarily restoring the patient to CP in preparation for HSCT.
      Imatinib, when administered at the standard dose of 400 mg/day is relatively well
      tolerated with major toxicities limited to myelo-suppression, edema, GI upset,
      rash, and muscle pain. Many of these toxicities are managed by decreasing the
      dose until the toxicity resolves. Imatinib is an inhibitor of cytochrome P450
      enzymes necessitating careful monitoring of concomitant medications metabolized
      by these enzymes. Resistance may develop to imatinib most often caused by the
      evolution of mutations blocking imatinib interactions with the BCR-ABL adenosine
      triphosphate (ATP) binding site. The second generation BCR-ABL inhibitor,
      dasatinib, can block the activity of many of these mutations; however, the T315I
      mutation, at present, is resistant to all available kinase inhibitors.
      Experimental drugs that block this mutation are just entering phase two clinical
      trials. CONCLUSION: The development of therapeutic agents targeting BCR-ABL has
      revolutionized the treatment of chronic myeloid leukemia (CML). Imatinib has
      successfully allowed CML patients to remain in CP for at least five years in 90%
      of patients. Dasatinib has activity against a number of Imatinib-resistant
      mutants providing an additional therapeutic option for these patients.

PMID- 18056933
TI  - Community-acquired skin infections remain treatable.

PMID- 18056934
TI  - Medicare updates outpatient payment system.

PMID- 18056935
TI  - County health system finds Medicare Part D rewarding.

PMID- 18056936
TI  - Trade group says thwarting drug counterfeiters remains challenging.

PMID- 18056937
TI  - Effect of linezolid on the occurrence of vancomycin-resistant enterococci.

PMID- 18056938
TI  - Dosage adjustments in hepatic dysfunction.

PMID- 18056940
TI  - An appreciation of 40 years.

PMID- 18056941
TI  - Providing feedback to enhance pharmacy students' performance.

PMID- 18056942
TI  - Extended-dosage-interval regimens of erythropoietic agents in chemotherapy
      induced anemia.
AB  - PURPOSE: The safety and efficacy of extended-dosage-interval regimens of
      erythropoiesis-stimulating agents (ESAs) for managing chemotherapy-induced anemia
      (CIA) are reviewed. SUMMARY: Anemia is a frequent complication of chemotherapy.
      The ESAs epoetin alfa and darbepoetin alfa have been shown to safely and
      effectively manage CIA; comparable outcomes have been demonstrated between
      epoetin alfa 40,000 units once weekly and darbepoetin alfa 200 microg every two
      weeks. These commonly prescribed regimens necessitate extra clinic visits by
      cancer patients receiving cyclic chemotherapy. ESA administration can now often
      be synchronized with a three-week chemotherapy cycle because of the recent
      approval of darbepoetin alfa 500 microg every three weeks for CIA. However, in
      the Phase III trial providing the basis for this new dosage recommendation, more
      than 70% of patients required a 40% reduction in the dosage, resulting in an
      average dose of 375 microg every three weeks. The extended-dosage-interval
      regimens have not been associated with an increase in cardiovascular or
      thrombotic adverse events. Extended-dosage-interval regimens of epoetin alfa are
      under investigation and may provide additional alternatives. Synchronizing ESA
      therapy with scheduled chemotherapy visits would help minimize disruptions for
      patients and caregivers and improve the use of health care resources. CONCLUSION:
      Administration of darbepoetin alfa every three weeks offers the convenience of
      synchronization of treatment with 21-day-cycle chemotherapy in many patients with
      CIA. Extended-dosage-interval regimens for epoetin alfa are being investigated
      and show promise.

PMID- 18056943
TI  - Edema in a patient receiving methadone for chronic low back pain.
AB  - PURPOSE: The case of a patient who developed edema after receiving methadone for
      chronic low back pain is reported. SUMMARY: A 45-year-old white woman developed
      edema in her lower extremities one week after starting methadone, etodolac, and
      gabapentin as part of her treatment for chronic low back pain. She was taking
      methadone as part of her treatment regimen to manage her pain in addition to
      other agents, including etodolac and gabapentin. After several days on this
      therapy, she developed edema and stated that she was "feeling drunk." At that
      time the etodolac and gabapentin were stopped, and the methadone dosage was
      increased. Several days later, the patient returned to the pain clinic,
      complaining of continued swelling. The methadone dosage was then decreased, and a
      diuretic was added to treat the edema; however, her edema did not resolve with
      the lower dosage of methadone. Methadone was then discontinued, and a fentanyl
      patch was prescribed. Prednisone was also prescribed, and the dosage of the
      diuretic was increased. The patient's symptoms resolved, and prednisone was
      ultimately tapered. The likelihood that the administration of methadone was
      related to the development of edema in this patient was determined to be
      probable. There have been a few cases reported in the literature regarding the
      development of edema with methadone use. In the cases reported, the edema
      developed after three to six months of methadone therapy. CONCLUSION: A patient
      with chronic low back pain developed edema one week after receiving methadone as
      part of her pain management regimen.

PMID- 18056944
TI  - Comparative cost-effectiveness of voriconazole and amphotericin B in treatment of
      invasive pulmonary aspergillosis.
AB  - PURPOSE: The comparative cost-effectiveness of voriconazole and amphotericin B in
      the treatment of invasive pulmonary aspergillosis (IPA) was examined. METHODS: A
      decision-tree model was constructed comparing 12-week treatment outcomes in a
      subset of patients enrolled in a clinical trial comparing initial treatment of
      IPA with amphotericin B versus voriconazole. Patients included those with IPA who
      underwent a thoracic computed tomographic (CT) scan at baseline. Cost and
      survival were estimated for those with and without a halo sign at baseline.
      Incremental cost-effectiveness ratios comparing voriconazole with amphotericin B
      were calculated for both patient subgroups. RESULTS: Patients with a halo sign
      had similar costs and better survival rates than those without the sign. Within
      the subgroup of patients with the sign, total costs were lower and survival rates
      higher for those treated with voriconazole than for those treated with
      amphotericin B. For patients without a halo sign, total costs and survival rates
      were higher for those treated with voriconazole versus amphotericin B.
      CONCLUSION: Among patients treated for IPA, those with a baseline CT halo sign,
      an early indicator of the condition, appeared to have better survival rates and
      lower health care costs compared with patients without the sign. In patients with
      the halo sign, survival rates were higher and costs were lower when voriconazole
      rather than amphotericin B was used as first-line treatment; survival was better
      with voriconazole than with amphotericin B when the halo sign was not present.
      Voriconazole was cost-effective compared with amphotericin B when the halo sign
      was present, but voriconazole's cost-effectiveness when the sign was not present
      depended on the cost per life saved.

PMID- 18056945
TI  - Stability of codeine phosphate in an extemporaneously compounded syrup.
AB  - PURPOSE: The stability of codeine phosphate in an extemporaneously compounded
      syrup is described. METHODS: Codeine phosphate 3-mg/mL syrup was prepared using
      commercially available Codeine Phosphate, USP, Sterile Water for Irrigation, USP,
      and Ora-Sweet syrup vehicle. Samples were stored in amber polyethylene
      terephthalate bottles with child-resistant caps. A second batch of codeine
      phosphate 3-mg/mL syrup was prepared and drawn into amber polyethylene oral
      syringes with silicon elastomer tips. All samples were stored at room temperature
      and in the dark. Samples were analyzed immediately and at 7, 14, 28, 42, 56, 70,
      and 98 days. Codeine phosphate concentrations were measured using a modified
      stability-indicating high-performance liquid chromatographic method. At each test
      interval, the density of the syrup was determined gravimetrically using a 10-mL
      amber oral syringe. Excessive degradation was defined as a greater than 7% loss
      of the initial concentration. RESULTS: The stock internal standard was stable for
      at least 98 days at room temperature. The compounded syrup retained more than 93%
      of the initial codeine phosphate concentration for at least 98 days at 22-25
      degrees C. No changes in color, clarity, or odor and no visible solids or
      microbial growth were observed in any sample. The pH of the syrup was initially
      4.2 and remained unchanged throughout the study. CONCLUSION: Codeine phosphate 3
      mg/mL in Ora-Sweet syrup vehicle was stable in both amber polyethylene
      terephthalate bottles and amber polyethylene oral syringes for at least 98 days
      when stored at 22-25 degrees C and protected from light.

PMID- 18056946
TI  - Effects of pharmacists' interventions on patient outcomes in an HIV primary care
      clinic.
AB  - PURPOSE: The effects of pharmacists' interventions on patient outcomes in an HIV
      primary care clinic were studied. METHODS: All study participants were referred
      to a pharmacist-managed drug optimization clinic (DOC) in a county-based HIV
      primary care clinic between November 1, 2003, and September 30, 2004. Patients
      were eligible for study participation if they were 18 years of age or older and
      gave informed consent to participate. Pharmacists' interventions were categorized
      as follows: patient education, addition of a medication, dosage adjustment,
      discontinuation of a medication, and interpretation of viral-resistance tests.
      Changes in baseline CD4+ T-lymphocyte counts and viral load were also measured
      over the study period. Toxicities related to highly active antiretroviral therapy
      were recorded and graded from 0 to 4, with 0 indicating no toxicity and 4
      indicating severe toxicity. Study participants used a standardized survey to
      measure their own health-related quality of life. Changes in CD4+ lymphocyte
      counts and viral load were analyzed using Student's t test and analysis of
      variance. Toxicity grades were analyzed using the Wilcoxon signed-rank test.
      RESULTS: A total of 34 patients completed the study. Pharmacists made a total of
      253 interventions, most of which were categorized as patient education. The mean
      CD4+ lymphocyte count increased from baseline levels by 54 +/- 78 cells/mm3 over
      the study period (p < 0.0002). The mean +/- S.D. reduction in circulating viral
      load over the study period was 1.02 log10 copies/mL ( p < 0.004). CONCLUSION: HIV
      infected patients who were managed by pharmacists in a DOC demonstrated
      significant improvement from baseline in their CD4+ lymphocyte counts, viral
      loads, and drug-related toxicities.

PMID- 18056948
TI  - Brief intervention protocol for assisting patients with tobacco cessation.

PMID- 18056947
TI  - Blood pressure management in acute hypertensive emergency.
AB  - PURPOSE: The frequency with which patients coming to an emergency room with
      hypertensive emergency received excessive or inadequate blood-pressure reduction
      was studied. METHODS: A retrospective chart review was conducted for all patients
      who were treated for hypertensive emergency at a 696-bed university teaching
      hospital between November 2003 and April 2004. Patients who received a continuous
      i.v. infusion of an antihypertensive agent for >30 minutes in the emergency
      department or the intensive care unit were included in the study. The primary
      outcomes measured were number of patients treated appropriately, number of
      patients treated excessively (reduction in mean arterial pressure [MAP] beyond
      25% at the end of the two-hour acute-phase treatment window), and number of
      treatment failures within the two-hour window. RESULTS: A total of 427 patients
      with hypertensive emergency were identified, of whom 47 met the study criteria.
      Fifteen patients (32%) were appropriately treated, 27 (57%) were excessively
      treated, and 5 (11%) had treatment failures during the two-hour acute-phase
      treatment period. Only 6 patients (13%) had been appropriately treated at six
      hours. Patients who were given nicardipine had a greater risk of an excessive MAP
      reduction at two hours than all other patients. One or more treatment-related
      adverse events occurred in 44 patients (94%). CONCLUSION: Excessive reduction of
      MAP was common among patients who came to an emergency department with
      hypertensive emergency.

PMID- 18056950
TI  - Exposure of human diploid fibroblasts to hypoxia extends proliferative life span.
AB  - Normal human mitotic cells do not proliferate indefinitely in culture but undergo
      a limited number of divisions and progressively reach a state of irreversible
      growth arrest, a process termed replicative senescence. Hypoxia is a situation of
      reduced oxygen concentration that relates to many physiological and
      pathophysiological conditions. In the current study we investigated the effects
      of oxygen concentration, in both normoxic and hypoxic conditions, on the
      proliferative capacity, cell viability, oxidative status, and protein expression
      of human embryonic diploid fibroblasts. Maintenance of WI38 and IMR90 cells in
      1.5% or 3% O(2) concentration significantly delayed the appearance of replicative
      senescence compared to cells grown in 20% O(2), induced the hypoxia-inducible
      factor-1alpha, and resulted in reduced expression levels of the key cell cycle
      modulators, namely p21 and p16. Moreover, cell exposure to short-term hypoxia
      affected their response to several cytotoxic agents, whereas adaptation to the
      hypoxic environment prior to the treatment had no impact on cell viability. These
      findings clearly identify that oxygen concentration plays a crucial role in
      regulating cellular life span of normal human cells.

PMID- 18056951
TI  - Cyclin D1 overexpression permits the reproducible detection of senescent human
      vascular smooth muscle cells.
AB  - The senescence of mitotic cells is hypothesized to play a causal role in
      organismal aging. Cultures of normal human cells become senescent in vitro as a
      result of a continuous decline in the mitotic fraction from cell turnover.
      However, one potential barrier to the evaluation of the frequency and
      distribution of senescent cells in tissues is the absence of a panel of robust
      markers for the senescent state. In parallel with an analysis of the growth
      kinetics of human vascular smooth muscle cells, we have undertaken transcriptomic
      comparisons of early- and late-passage cultures of human vascular smooth muscle
      cells to identify potential markers that can distinguish between senescent and
      growth-competent cells. A wide range of genes are upregulated at senescence in
      human vascular smooth muscle cells. In particular, we have identified a 12-fold
      upregulation of expression in the cyclin D1 message, which is reflected in a
      concomitant upregulation at the protein level. Quantitative cytochemical analysis
      of senescent and growing vascular smooth muscle cells indicates that cyclin D1
      reactivity is a considerably better marker of replicative senescence than
      senescence-associated beta-galactosidase activity. We have applied this new
      marker (in combination with Ki67, COMET, and TUNEL staining) to the study of
      human vascular smooth muscle cells treated with resveratrol, a putative anti
      aging molecule known to have significant effects on cell growth.

PMID- 18056952
TI  - Morphological changes associated with aging: age spots and the microinflammatory
      model of skin aging.
AB  - Affymetrix gene-expression analysis was performed on mRNAs from involved and
      noninvolved skin biopsies from three volunteers with Lentigo senilis. Of the
      42,000 transcripts scanned, 17 were downregulated (<1.4 times below the control
      level) and 23 were upregulated (>1.9 times above the control level). A serine
      peptidase gene was downregulated in keeping with the suggestion that age spots
      are associated with impaired melanin degradation. Three genes involved in the
      keratinization and synthesis and the organization of fibers in the basement
      membrane were downregulated, two metalloproteinase genes were upregulated, as
      were six genes associated with the inflammatory response, in keeping with the
      postulate that the visible aspects of aged skin are causally linked with a
      microinflammatory response. The regulation of five genes associated with the Wnt
      family was altered. Antiapoptotic genes were downregulated, and six genes
      associated with transmembrane transport were upregulated.

PMID- 18056953
TI  - Molecular mechanisms of skin aging: state of the art.
AB  - The process of skin aging in humans is complex and is induced by multiple
      factors, including genetic and various environmental ones. In particular, the
      superposition of environmental factors, such as UV irradiation on skin, results
      in massive wound-like morphological alterations mainly of the dermis. In sun
      protected areas the most pronounced changes occur within the epidermis and affect
      mostly the basal cell layer. As a result, while sun-protected aged skin appears
      thin, finely wrinkled, and dry, photoaged skin is characterized by deep wrinkles,
      laxity, and roughness. Although the fundamental mechanisms are still poorly
      understood, a growing body of evidence points toward the involvement of multiple
      pathways in the generation of aged skin. Recent data obtained by expression
      profiling studies and studies of progeroid syndromes (e.g., Hutchinson-Gilford
      progeria, Werner syndrome, Rothmund-Thomson syndrome, Cockayne syndrome, ataxia
      teleangiectasia, and Down syndrome) illustrate that among the most important
      biological processes involved in skin aging are alterations in DNA repair and
      stability, mitochondrial function, cell cycle and apoptosis, ubiquitin-induced
      proteolysis, and cellular metabolism. One of the major factors that has been
      proposed to play an exquisite role in the initiation of aging is the
      physiological hormone decline occurring with age. However, hormones at age
      specific levels may not only regulate age-associated mechanisms but also regulate
      tumor-suppressor pathways that influence carcinogenesis. Understanding the
      molecular mechanisms of aging may open new strategies in dealing with the various
      diseases accompanying aging, including cancer.

PMID- 18056954
TI  - Acquisition of oxidative DNA damage during senescence: the first step toward
      carcinogenesis?
AB  - As a result of time and cumulative divisions in vitro and in vivo, normal cells
      enter an irreversible nonproliferative state termed replicative or cellular
      senescence that is thought to contribute to organism aging. Both telomere
      shortening and cumulative oxidative damage were shown to contribute to
      senescence, probably acting at different degrees according to proliferation
      index, cell type, or environment. Because of its associated cohort of damages and
      irreversible cell-cycle arrest induced by shortened telomeres, senescence is
      commonly considered as a tumor-suppressor mechanism that stops the proliferation
      of genetically altered cells (i.e., potentially cancerous). However, the
      incidence of the most frequent cancers in humans, carcinomas, exponentially
      increases with age; the phenotypes of progeroid syndromes are often associated
      with an increase in tumor incidence, and inversely when aging is delayed by
      caloric restriction, the cancer incidence decreases. How can this positive link
      between aging and tumorigenesis be explained if senescence is a tumor-suppressor
      mechanism? The present article considers data and arguments supporting a
      protumoral role of senescence. We focus on the importance of the oxidative damage
      that targets DNA during senescence. Indeed, because of its mutagenic effects,
      oxidative damage could affect oncogenes and/or tumor-suppressor genes in some
      senescent cells, hence promoting their evolution toward initiated cancer cells.
      This mechanism could be particularly relevant for age-associated carcinomas
      because senescence in epithelial cells is driven more by oxidative stress than by
      telomere shortening.

PMID- 18056955
TI  - Effect of the histone deacetylase inhibitor trichostatin a in human peripheral
      blood lymphocytes as a function of donor age.
AB  - The histone deacetylase inhibitor trichostatin A (TSA) is a promising agent for
      the treatment of certain types of cancers alone or in synergistic combination
      with other anticancer agents. One of the advantages of the use of histone
      deacetylase inhibitors, such as TSA, is that its effects have been found to be
      more potent toward cancer cells compared to normal cells. The effect of
      anticancer agents on the immune system, and on lymphocytes in particular, is of
      major importance to the success of anticancer regimens. In this respect,
      information documenting the effect of such agents on normal lymphocytes compared
      to malignant cells may be of significant value for the successful designing of
      clinical protocols. Moreover, the parameter of age may be a factor in the
      differential effects of such protocols. Histone deacetylase inhibitors lead to
      the accumulation of acetylated histones and, depending on the cell type, may
      induce either apoptosis, cell cycle arrest, or differentiation. Previous work
      from our lab has shown that TSA induces the accumulation of histone H4
      acetylation and apoptosis in human peripheral blood lymphocytes. In light of the
      above, we have extended our investigation of the effects of TSA on human
      lymphocytes to include the parameter of age, which has not been previously
      studied. Our results show that TSA induces apoptosis of lymphocytes from donors
      of all age groups, but no age-related changes in the levels of apoptosis are
      observed.

PMID- 18056956
TI  - Transient increased extracellular release of H2O2 during establishment of UVB
      induced premature senescence.
AB  - In this work, we found that extracellular release of H(2)O(2) is 1.5- to 6-fold
      higher in skin human diploid fibroblasts exposed to UVB in conditions inducing
      premature senescence when compared to control cells without exposure to UVB. The
      apparent decrease in H(2)O(2) production from 0 to 72 h after the last exposure
      to UVB was not due to increased enzymatic activity of catalase or glutathione
      peroxidase.

PMID- 18056957
TI  - Importance of the lon protease in mitochondrial maintenance and the significance
      of declining lon in aging.
AB  - Mitochondria are a major intracellular source of free radicals and related
      oxidants. It is generally agreed that the mitochondrial production of such
      reactive oxygen and nitrogen species increases with age. Antioxidant systems in
      the mitochondria play an important role in limiting the amount of oxidative
      damage to tolerable levels. The Lon protease degrades oxidatively modified
      proteins in the mitochondrial matrix, a function similar to that of the 20S
      proteasome in the cytoplasm. Recently it was shown that inactive aconitase, a
      preferential substrate for the Lon protease, might be involved in the maintenance
      of the mitochondrial genome. Lon protease expression and activity declines with
      age, which may contribute to the accumulation of the oxidatively modified protein
      aggregates typically observed in aging and diseased cells. In addition, Lon has
      multiple functions, such as DNA binding and chaperone activity, for the assembly
      of respiratory complexes in the Electron Transport Chain. Taken together, Lon and
      aconitase may be key players in the maintenance of mitochondrial homeostasis
      under conditions of stress, and (partial) compromise of their function may
      contribute to both aging and degenerative diseases.

PMID- 18056958
TI  - Protein oxidative modifications and replicative senescence of WI-38 human
      embryonic fibroblasts.
AB  - The age-related accumulation of oxidized proteins is dependent on the balance
      between the generation of oxidatively modified proteins and their elimination by
      protein degradation and repair systems. Previous studies have demonstrated that
      replicative senescence represents a valid model of in vitro aging and that
      senescent cells do accumulate oxidized proteins while both proteasome, which is
      the major intracellular proteolytic system implicated in the removal of abnormal
      and oxidized proteins, and the oxidized protein-repair enzymes, methionine
      sulfoxide reductases, are being impaired. Declining proteasome activity with age
      has been attributed to decreased proteasome subunits expression and/or
      inactivation upon alteration of proteasome subunits, as well as accumulation of
      endogeneous inhibitors, such as highly oxidized and cross-linked proteins. To
      gain further insight into the mechanisms that might be implicated in the
      decreased activity of the proteasome with replicative senescence, the occurrence
      of proteins modified by glycoxidation and conjugation by lipid peroxidation
      products has been investigated in senescent cells. Indeed, such modification as
      the formation of protein adducts with the lipid peroxidation product 4-hydroxy-2
      nonenal can generate cross-linked proteins that become resistant to degradation
      by the proteasome and can act as inhibitors of the proteasome. Using specific
      antibodies that recognize glycoxidation and lipid peroxidation adducts on
      proteins, both modifications were demonstrated and found to increase in senescent
      cells when compared with young fibroblasts. Moreover, the patterns of modified
      proteins obtained after separation by SDS gel electrophoresis were indicative of
      preferential protein targets for both modifications.

PMID- 18056959
TI  - Lipofuscin: formation, distribution, and metabolic consequences.
AB  - One of the highlights of postmitotic aging is the intracellular accumulation of
      highly oxidized and cross-linked proteins, known as lipofuscin. Lipofuscin is
      insoluble and not degradable by lysosomal enzymes or the proteasomal system,
      which is responsible for the recognition and degradation of misfolded and
      oxidatively damaged proteins. These aggregates have been found in various cell
      types, including heart, liver, kidney, neuronal tissue, and dermal tissue, and
      are associated with the life span of a single postmitotic cell and, consequently,
      of the whole organism. Lipofuscin formation appears to depend on the rate of
      oxidative damage to proteins, the functionality of mitochondrial repair systems,
      the proteasomal system, and the functionality and effectiveness of the lysosomes.
      This review highlights the current knowledge of the formation, distribution, and
      effects of lipofuscin in mammalian cells.

PMID- 18056960
TI  - Stress-mediated hormetic modulation of aging, wound healing, and angiogenesis in
      human cells.
AB  - Aging is amenable to intervention and prevention by mild stress-induced hormesis.
      Previously, we have reported that repeated mild heat stress has antiaging and
      other beneficial effects on growth and a range of cellular and biochemical
      characteristics of normal human skin fibroblasts and keratinocytes undergoing
      aging in vitro. We have also established a model system of sugar-induced
      premature senescence in human cells, which can be useful for monitoring the
      protective and hormetic effects of other treatments. We have now initiated
      studies on testing the hormetic effects of glyoxal and heat shock on the wound
      healing capacity of skin fibroblasts and on the angiogenic ability of endothelial
      cells. The effects of glyoxal on the extent of wound closure in vitro showed a
      typical biphasic hormetic curve with 20-40% stimulation at lower doses (up to
      0.125 mmol) and more than 50% inhibition at concentrations above 0.5 mmol. In the
      case of angiogenesis by endothelial cells, measured by the standard tube
      formation assay on Matrigel, a prior exposure to mild heat shock at 41 degrees C
      for 1 h increased the total tube length and total number of junctions by 30-60%
      and 10-14%, respectively. In contrast, a severe heat shock at 42.5 degrees C had
      slightly inhibitory effects on total tube length and the number of junctions.
      These data add to the ever-growing body of evidence in support of the view that
      mild stress-induced hormesis can be a useful approach for the modulation,
      intervention, and prevention of aging and age-related impairments.

PMID- 18056961
TI  - Real aging retardation in humans through diminishing risks to health.
AB  - Many biologists do not believe that practical means of postponing human aging are
      currently available. Human aging appears to result from the random accumulation
      of damage in cells, tissues, or the organism as a whole that occurs over the
      lifetime of the organism and increases the probability of death. It is possible
      to decrease the rate of this accumulation of damage in humans, as already does
      occur in developed countries. Initiating the sorts of changes that extend healthy
      life span has been a relatively slow process, because it has been a byproduct of
      general economic development, but it could be made to proceed more rapidly. Our
      research shows that it is possible to postpone age-related changes by up to 20
      years, by using what is already known about avoiding discomfort and risk factors
      to health in practical application.

PMID- 18056962
TI  - Zinc, metallothioneins, and longevity--effect of zinc supplementation: zincage
      study.
AB  - Aging is an inevitable biological process that is associated with gradual and
      spontaneous biochemical and physiological changes and increased susceptibility to
      diseases. Because nutritional factors are involved in improving immune functions,
      metabolic harmony, and antioxidant defense, some nutritional factors, such as
      zinc, may modify susceptibility to disease and promote healthy aging. In vitro
      (human lymphocytes exposed to endotoxins) and in vivo (old or young mice fed with
      low zinc dietary intake) studies revealed that zinc is important for immune
      efficiency (innate and adaptive), antioxidant activity (supeoxide dismutase), and
      cell differentiation via clusterin/apolipoprotein J. Intracellular zinc
      homeostasis is regulated by metallothioneins (MT) via ion release through the
      reduction of thiol groups in the MT molecule. This process is crucial in aging
      because high MT levels are not able to release zinc, resulting in low
      intracellular free ion availability for biological functions. Improvement in
      these functions occurs in the elderly after physiological zinc supplementation.
      In this study, the selection of elderly subjects for zinc supplementation is
      discussed in relation to the genetic background of MT and pro-inflammatory
      cytokines, such as interleukin-6, because the latter is involved both in MT-gene
      expression and in intracellular zinc homeostasis.

PMID- 18056963
TI  - Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during
      aging.
AB  - Administration of an orally active agonist (MK-0677) of the growth hormone
      secretagogue receptor (GHS-R1a) to elderly subjects restored the amplitude of
      endogenous episodic growth hormone (GH) release to that of young adults.
      Functional benefits include increased lean mass and bone density and modest
      improvements in strength. In old mice, a similar agonist partially restored
      function to the thymus and reduced tumor cell growth and metastasis. Treatment of
      old mice with the endogenous GHS-R1a agonist ghrelin restored a young liver
      phenotype. The mechanism involves inhibition of cyclin D3:cdk4/cdk6 activity and
      increased protein phosphatase-2A (PP2A) activity in liver nuclei, which
      stabilizes the dephosphorylated form of the transcription factor C/EBPalpha
      preventing the age-dependent formation of the C/EBPalpha-Rb-E2F4-Brm nuclear
      complex. By inhibiting formation of this complex, repression of E2F target genes
      is de-repressed and C/EBPalpha regulated expression of Pepck, a regulator of
      gluconeogenesis, is normalized, thereby restoring a young liver phenotype. In the
      brain, aging is associated with decline in dopamine function. We investigated the
      potential neuromodulatory role of GHS-R1a on dopamine action. Neurons were
      identified in the hippocampus, cortex, substantia nigra, and ventral tegmental
      areas that coexpressed GHS-R1a and dopamine receptor subtype-1 (D1R). Cell
      culture studies showed that, in the presence of ghrelin and dopamine, GHS-R and
      D1R form heterodimers, which modified G-protein signal transduction resulting in
      amplification of dopamine signaling. We speculate that aging is associated with
      deficient endogenous ghrelin signaling that can be rescued by intervention with
      GHS-R1a agonists to improve quality of life and maintain independence.

PMID- 18056964
TI  - Functional significance of minor structural and expression changes in stress
      chaperone mortalin.
AB  - Mortalin is one of the highly conserved heat-shock chaperones. Some of the
      established features of mortalin include its various subcellular localizations,
      multiple binding partners, and differential subcellular distribution in normal
      and immortal cells. It inhibits nuclear translocation, transcriptional
      activation, and control of centrosome-duplication functions of p53. It also
      functions as an adaptive protein in a variety of stress-response mechanisms and
      contributes to human carcinogenesis. Interestingly, minor alterations in its
      structure and level of expression may lead to drastic biological consequences
      (for example, Myelodysplastic syndrome and old age pathologies, such as
      Alzheimer's and Parkinson's disease). Besides being validated as a reliable
      target for cancer therapy, mortalin also warrants attention from the perspectives
      of management of old-age diseases and healthy aging.

PMID- 18056965
TI  - GRO-alpha: a potential marker for cancer and aging silenced by RNA interference.
AB  - Age-regulated genes may serve as markers of aging, enabling assessment of
      physiological aging independent of chronological age. One gene with transcripts
      that increase in abundance with age in human organs, inter alia in epithelial
      skin cells, is the chemokine growth-regulated protein alpha (GRO-alpha). When
      chemokines, such as GRO-alpha, become disregulated so that they are chronically
      expressed, tissue damage, angiogenesis, and tumorigenesis can follow. To consider
      the role of GRO-alpha as a potential marker for aging and cancer, we compared the
      transient knockdown of GRO-alpha by RNA interference in the human sebaceous gland
      cell line SZ95, which behaves like normal human sebocytes, and in the melanoma
      cell line A375, which originates from a primary human tumor. The reduced GRO
      alpha RNA expression, of about 75% in SZ95 sebocytes and 58% in A375 melanoma
      cells, has functional consequences in normal aged cells and in cancer cells.
      Silencing of the proangiogenic chemokine GRO-alpha is proportionally correlated
      with interleukin-6 (IL-6), IL-8 and vascular endothelial growth factor secretion
      in both cell types. Thus, GRO-alpha may be a novel diagnostic marker for age
      related pathology, including cancer.

PMID- 18056966
TI  - Caspase-3 and Bcl-2 expression in aging in adrenal zona reticularis after
      dexamethasone administration.
AB  - Adrenocortical cell death by apoptosis is a common finding when
      adrenocorticotropic hormone is suppressed. Despite the well-known final
      structural features exhibited by those cells, data on the mechanisms preceding
      these final events are lacking. In this study, after 3 days of dexamethasone
      administration to rats of different ages, rat adrenals were processed for
      immunocytochemical study. In the zona reticularis, there was evidence of the
      activation of Bcl-2 and caspase-3 proteins. Beyond a small age-related increase
      in labeled cells, the number of cells presenting colocalization for both proteins
      was noteworthy. The results confirm the involvement of Bcl-2 and caspase-3
      proteins in the apoptotic pathway and suggest their simultaneous intervention.

PMID- 18056967
TI  - Nutraceutical strategy in aging: targeting heat shock protein and inflammatory
      profile through understanding interleukin-6 polymorphism.
AB  - The aging process is paralleled by two- to fourfold increases in plasma/serum
      levels of inflammatory mediators, such as cytokines and acute-phase proteins. In
      this study we assessed the inflammatory profile and polymorphism of healthy
      elderly subjects and the influence of a nutraceutical supplement. Forty elderly,
      generally healthy subjects were recruited, divided into two matched groups, and
      given either a fermented papaya preparation 9 g/day by mouth or the same amount
      of placebo. Treatments were carried out in a cross-over manner with a 3-month
      supplementation period followed by a 6-week washout period between treatments.
      Ten healthy young subjects served as controls. Interleukin-6 (IL-6) promoter -174
      G/C polymorphism genotype was determined together with blood levels for redox
      status, proinflammatory cytokines, high sensitivity C-reactive protein, and serum
      70 kDa heat shock protein (Hsp70) concentrations. Tumor necrosis factor-alpha and
      IL-6 were higher in elderly subjects (P < 0.05 versus young controls). The
      concentration of Hsp70 inversely correlated with markers of inflammation in -174
      G/C-negative subjects (r = 0.62, P < 0.05). Nutraceutical intervention normalized
      the inflammatory parameters (P < 0.05) with a rise of Hsp70 (P < 0.05). This
      suggests that healthy elderly individuals may have a proinflammatory profile
      playing as a downregulating factor for inducible Hsp70, particularly if -174 G/C
      negative. A nutraceutical intervention seems able to beneficially modulate such a
      phenomenon.

PMID- 18056968
TI  - Role of TLR4 polymorphisms in inflammatory responses: implications for
      unsuccessful aging.
AB  - The total burden of infection at various sites may affect the progression of
      atherosclerosis and Alzheimer's disease (AD), the risk being modulated by host
      genotype. The role of lipopolysaccharide (LPS) receptor TLR4 is paradigmatic. It
      initiates the innate immune response against gram-negative bacteria, and TLR4
      single nucleotide polymorphisms (SNPs), such as +896A/G, known to attenuate
      receptor signaling, have been described. This SNP shows a significantly lower
      frequency in patients affected by myocardial infarction or AD. Thus, people
      genetically predisposed to developing lower inflammatory activity seem to have
      less chance of developing cardiovascular disease (CVD) or AD. In the present
      report, to validate this hypothesis, the levels of the eicosanoids, leukotriene
      B4 (LTB4) and prostaglandin E2 (PGE2), known to be involved as mediators in age
      related diseases, were determined by an enzyme-linked immunosorbent assay in
      supernatants from a whole blood assay, after stimulation with subliminal doses of
      LPS from Escherichia coli. The samples, genotyped for the +896A/G SNP, were
      challenged with LPS for 4, 24, and 48 h. Both LTB4 and PGE2 values were
      significantly lower in carriers bearing the TLR4 mutation. Therefore, the
      pathogen burden, by interacting with the host genotype, determines the type and
      intensity of the inflammatory responses accountable for proinflammatory status,
      CVD, AD, and unsuccessful aging (i.e., age-related inflammatory diseases).

PMID- 18056969
TI  - ProNGF, sortilin, and age-related neurodegeneration.
AB  - Several studies have sought to demonstrate that neurodegeneration during disease
      and in old age is associated with reduced neurotrophic support. Little positive
      evidence has been forthcoming, either in relation to the availability of
      neurotrophins or to expression and function of the relevant receptors. Recently,
      a novel way in which neurotrophins could contribute to neurodegeneration has been
      suggested. In contrast to the well-known neurotrophic functions of the mature
      beta-form of nerve growth factor (mNGF), its precursor proNGF has recently been
      shown to be abundant in the adult brain and in the brains of patients with
      Alzheimer's disease. proNGF is synthesized as 25 and 32 kDa isoforms, which are
      glycosylated to form a principal 40 kDa species. Studies of the cortical targets
      of NGF-responsive basal forebrain neurons show that the 40 kDa form of proNGF is
      secreted in response to nerve stimulation, along with the proteases needed to
      generate the 13 kDa mNGF, or to degrade it. We have recently found that levels of
      40 kDa proNGF are elevated in the aging brain and also in targets of peripheral
      NGF-responsive neurons. proNGF has been shown to be neurotoxic when bound in a
      heterotrimer with the p75 receptor and the receptor sortilin (identical to the
      neurotensin receptor NTS3). Interestingly, we find that sortilin levels increase
      in aged central and peripheral neurons, perhaps making these neurons more
      vulnerable to age-related increases in proNGF. Whether elevated levels of proNGF
      in targets or of sortilin in neurons contribute to known patterns of age- and
      disease-related neurodegeneration has not been previously investigated. Using in
      vitro models, our preliminary data now indicate that proNGF is indeed neurotoxic
      for aged, but not young, NGF-responsive basal forebrain and sympathetic neurons
      and that blockade of sortilin rescues proNGF-induced cell death. We therefore
      propose that increased proNGF in targets combined with increased sortilin
      expression in projecting neurons contributes to age-related neuronal atrophy and
      degeneration.

PMID- 18056970
TI  - Identification of fasting-induced genes in the rat hypothalamus: relationship
      with neuroprotection.
AB  - During food shortage, organisms activate defense mechanisms to maximize their
      chance of survival. At least in part, these responses are triggered by changes in
      hormonal status and neural status during starvation. The hypothalamus is
      organized as a collection of distinct autonomously active nuclei and is
      considered to play crucial roles in these survival responses. To isolate factors
      involved in these pathways, we carried out suppression subtractive hybridization
      analyses using complementary DNAs (cDNA) from the hypothalami of fasted and fed
      rats. We identified four genes, namely ubiquitin-conjugating enzyme E2D 3
      (UBE2D3), cAMP-dependent protein kinase C beta subunit (PKCbeta), excitatory
      amino acid carrier 1 (EAAC1), and ferritin heavy polypeptide 1 (Fth1), that were
      upregulated after a 48-h fast compared to the fed status. According to previous
      reports, these genes have been implicated in protection against neuronal cell
      death under various neurodegenerative stresses, such as hypoxia-ischemia and
      oxidative stress. Thus, the increased expressions of the genes identified in the
      present study may have protective effects against neural damage that could
      otherwise result in cell death.

PMID- 18056971
TI  - Acute myocardial infarction and proinflammatory gene variants.
AB  - We identified four genetic risk sets for acute myocardial infarction (AMI) from
      information on functional gene variants that favor inflammation or modulate
      cholesterol metabolism: IL6 -174 G/C, TNF -308 G/A, IL10 -1082 G/A, SERPINA3 -51
      G/T, IFNG +874 T/A, HMGCR -911 C/A, and APOE epsilon2/3/4; 316 patients and 461
      healthy subjects, all Italian. Putative risk alleles are shown underlined. The
      sets were identified using grade-of-membership analysis. Membership scores in the
      sets are automatically generated for individuals. The 'low intrinsic risk' set
      had alleles that downregulate inflammation and cholesterol synthesis (IL6, TNF,
      ILl0, HMGCR). 'AMI across a broad age range' carried multiple proinflammatory
      alleles (IL6, TNF, IL10, SERPINA3): All 72 persons like this set were affected
      yet had relatively low plasma cholesterol levels. 'A subset of AMI in middle age'
      had numerous proinflammatory alleles (IL6, TNF, SERPINA3, IFNG, HMGCR). 'AMI
      after age 80' had a reduced risk set (IL6, IL10, IFNG). A total of 95% of cases
      had >/=50% membership in the high intrinsic risk sets. We conclude that
      proinflammatory gene variants taken together strongly determine an individual's
      risk for myocardial infarction. This information may better define the
      pathogenesis of myocardial infarction and identify individuals who might benefit
      from early interventions.

PMID- 18056972
TI  - Bone mineral density in ukrainian women of different age.
AB  - We determined the bone mineral density (BMD) of normal Ukrainian female subjects
      and compared results with USA-European reference data. The research was conducted
      at the Ukrainian Scientific-Medical Centre for the Problems of Osteoporosis and
      included 353 women aged 20-79 years. Conventional BMD measurements of the spine
      (L1-L4 in the anterior-posterior position), proximal femur (neck, Ward's
      triangle, and trochanter regions), and radial shaft (33% site) were determined by
      dual-energy X-ray absorptiometry using a densitometer Prodigy. Age-related
      changes in BMD were similar in form to those of USA-European reference data. We
      found that the BMD values of spine for Ukrainian women of 50-59 years were lower
      than published values. Regression analyses showed that weight was a significant
      predictor of female spine and femur BMD for both the premenopausal and the
      postmenopausal decades. Age was a significant predictor of female spine BMD in
      the 50- to 79-year age group. The prevalence of osteoporosis and osteopenia for
      Ukrainian women was 11% at the femoral neck and 20% and 24% at the spine and
      radial shaft, respectively.

PMID- 18056973
TI  - Sex-specific effects of the DAF-12 steroid receptor on aging in Caenorhabditis
      elegans.
AB  - Sex differences in longevity and aging are seen throughout the animal kingdom.
      These are likely to result, in part, from sex differences in endocrinology. In
      the nematode Caenorhabditis elegans, males are the longer-lived sex. Here we
      explore the possibility that sex differences in insulin/insulin-like growth
      factor 1 (IGF-1) and steroid endocrinology contribute to this sex difference in
      aging by studying C. elegans populations in liquid culture. We report that in
      hermaphrodite populations, mutational loss of the DAF-12 steroid receptor
      affected life span as in previous plate-culture studies: mutant longevity is
      suppressed in a weak daf-2 insulin/IGF-1 receptor mutant but enhanced in a
      stronger daf-2 mutant. However, in males, mutation of daf-12 had little effect on
      aging in either weak or strong daf-2 mutants. Moreover, while mutation of daf-12
      marginally reduced life span in daf-2(+) hermaphrodites, as in plate-cultured
      populations, it did not in daf-2(+) males. These results could imply that in C.
      elegans, as in mammals, sex differences in steroid endocrinology contribute to
      sex differences in aging.

PMID- 18056974
TI  - Modulating longevity in Drosophila by over- and underexpression of glutamate
      cysteine ligase.
AB  - A notable extension of life span (up to 50%) was achieved in Drosophila
      melanogaster when the catalytic subunit of glutamate-cysteine ligase (GCLc) was
      overexpressed in neuronal tissue, while a moderate increase (up to 24%) was
      observed when the modulatory subunit of GCL (GCLm) was overexpressed globally. We
      sought to identify specific tissue domains that are particularly sensitive to the
      beneficial effects of GCLc overexpression. Overexpression of GCLc using the
      mushroom body driver (OK107-GAL4) had a small but significant beneficial effect
      on longevity (approximately 12%) while overexpression in serotonergic (MZ360
      GAL4) neurons or dopaminergic and serotonergic neurons (Ddc-GAL4) had small,
      nonsignificant effects on longevity. A significant beneficial effect (12-13%) was
      also observed using the C23-GAL4 transverse muscle driver. Finally, a low-level
      global driver (armadillo) was shown to increase life span significantly (15%). A
      series of mutant and knockdown studies were also carried out. Reduction of GCLm
      by > 95% had no discernable effect on longevity or resistance to oxidative
      stress. In contrast, knockdown of GCLc by 30-70% using an RNAi-hairpin strategy
      had a significant effect, resulting in greater sensitivity to H(2)O(2) and
      reduced survivorship under normal conditions varying from a 50% reduction in
      median life span to lethality. A GCLc null allele was identified and shown to be
      recessive lethal. Overall, this study demonstrates that the longevity effects of
      GCLc are dependent on dosage and that there are specific tissues (mushroom
      bodies, motor neurons, and transverse muscle cells) particularly sensitive to the
      benefits of GCLc overexpression.

PMID- 18056976
TI  - Protein synthesis is a novel determinant of aging in Caenorhabditis elegans.
AB  - Protein synthesis is a tightly regulated cellular process that affects growth,
      reproduction, and survival in response to both intrinsic and extrinsic cues, such
      as nutrient availability and energy levels. A pronounced, age-related decline of
      the total protein synthesis rate has been observed in many organisms, including
      humans. The molecular mechanisms underlying this decline and their role in the
      aging process remain unclear. A series of recent studies in the nematode,
      Caenorhabditis elegans, have revealed a novel link between protein synthesis and
      aging. Remarkably, these research findings, in their totality, converge to
      indicate that reduction of mRNA translation prolongs life in worms. Signal
      transduction cascades implicated in aging, such as the insulin/insulin growth
      factor-1 pathway, interface with mechanisms regulating protein synthesis via a
      battery of key mRNA translation factors. Are the effects of these pathways on
      aging mediated, in part, by alterations in protein synthesis? This is an
      intriguing possibility in light of the latest discoveries. Whether attenuation of
      protein synthesis promotes longevity across different phyla is an additional
      important matter. Here, we survey work associating protein synthesis with aging
      and discuss the basis of life-span extension under conditions that attenuate
      protein synthesis.

PMID- 18056975
TI  - Modeling Werner Syndrome in Drosophila melanogaster: hyper-recombination in flies
      lacking WRN-like exonuclease.
AB  - Human progeroid Werner syndrome provides the current best model for analysis of
      human aging, recapitulating many aspects of normal aging as a result of mutation
      of the WRN gene. This gene encodes a RecQ-type helicase with additional
      exonuclease activity. While biochemical studies in vitro have proven invaluable
      in determining substrate specificities of the WRN exonuclease and helicase, it
      has been difficult to dissociate the two key enzyme activities in vivo. We are
      developing Drosophila as a model system for analysis of WRN function; the
      suitability of Drosophila for extensive and sophisticated genetic manipulation
      permits us to investigate regulatory pathways and the impact of WRN loss at
      organismal, cellular, and molecular levels. BLASTP screening of the Drosophila
      genome with human WRN sequence allowed us to identify three RecQ helicases with
      strong homology to human WRN, a presumed helicase component of the spliceosome,
      and two DEAH-box putative RNA helicases with weaker WRN homology. None of these
      helicases contain a WRN-like exonuclease domain, but two potential WRN-like
      exonucleases in flies encoded by the loci CG7670 and CG6744 were also identified
      in the BLAST search. CG6744 and CG7670 are more closely related to human WRN than
      to each other. We have obtained a fly strain with a piggyBac insertional mutation
      within the CG6744 locus, which decreases expression of the encoded mRNA. Such
      flies show elevated levels of somatic recombination. We suggest that WRN-like
      exonuclease activity is critical in maintaining genomic integrity in flies.

PMID- 18056977
TI  - Nonpathological senescence arises from unsuitable external influences.
AB  - One of the most exciting events in current biogerontology is the elucidation of
      environmental control over the rate of aging. Many observations suggest that
      appropriate external stimuli can ameliorate the state of various biological
      entities and even rejuvenate them. Recent findings support the possibility that
      nonpathological aging of cells may be caused solely by external signals and
      moreover that this aging might be reversible. We have extended this principle to
      the level of the whole organism. We have suggested that a range of natural
      environmental conditions exists that corresponds to adequate vital activity
      within which an organism can maintain optimal functioning, renew itself, and
      remain ageless. But the environmental mortality of such organisms in natural
      niches is rather high. To reduce this mortality, the organism requires a milder
      but less stimulating environment in the presence of which (below some threshold
      level), the organism's renewal process becomes incomplete and the organism starts
      to age. Nevertheless, an age-dependent increase in the mortality rate due to
      senescence can be compensated for by a significant initial reduction in mortality
      due to environmental causes. The moderate present-day increase of life expectancy
      is the result of just such an initial mortality reduction. Living in a safe
      environment along with simulation of natural external positive influences or
      adequate responses to negative influences can decelerate, stop, and even reverse
      aging as well as considerably extend mean and extreme life span.

PMID- 18056978
TI  - Multiple neuroendocrine pathways mediate seasonal immunity.

PMID- 18056979
TI  - Key contributions of the Na+/H+ exchanger subunit 1 and HCO3- transporters in
      regulating neuronal cell fate in prolonged hypoxia.

PMID- 18056980
TI  - Muscle metabolic responses to exercise above and below the "critical power"
      assessed using 31P-MRS.
AB  - We tested the hypothesis that the asymptote of the hyperbolic relationship
      between work rate and time to exhaustion during muscular exercise, the "critical
      power" (CP), represents the highest constant work rate that can be sustained
      without a progressive loss of homeostasis [as assessed using (31)P magnetic
      resonance spectroscopy (MRS) measurements of muscle metabolites]. Six healthy
      male subjects initially completed single-leg knee-extension exercise at three to
      four different constant work rates to the limit of tolerance (range 3-18 min) for
      estimation of the CP (mean +/- SD, 20 +/- 2 W). Subsequently, the subjects
      exercised at work rates 10% below CP (<CP) for 20 min and 10% above CP (>CP) for
      as long as possible, while the metabolic responses in the contracting quadriceps
      muscle, i.e., phosphorylcreatine concentration ([PCr]), P(i) concentration
      ([P(i)]), and pH, were estimated using (31)P-MRS. All subjects completed 20 min
      of <CP exercise without duress, whereas the limit of tolerance during >CP
      exercise was 14.7 +/- 7.1 min. During <CP exercise, stable values for [PCr],
      [P(i)], and pH were attained within 3 min after the onset of exercise, and there
      were no further significant changes in these variables (end-exercise values = 68
      +/- 11% of baseline [PCr], 314 +/- 216% of baseline [P(i)], and pH 7.01 +/-
      0.03). During >CP exercise, however, [PCr] continued to fall to the point of
      exhaustion and [P(i)] and pH changed precipitously to values that are typically
      observed at the termination of high-intensity exhaustive exercise (end-exercise
      values = 26 +/- 16% of baseline [PCr], 564 +/- 167% of baseline [P(i)], and pH
      6.87 +/- 0.10, all P < 0.05 vs. <CP exercise). These data support the hypothesis
      that the CP represents the highest constant work rate that can be sustained
      without a progressive depletion of muscle high-energy phosphates and a rapid
      accumulation of metabolites (i.e., H(+) concentration and [P(i)]), which have
      been associated with the fatigue process.

PMID- 18056981
TI  - Interleukin-6 and cachexia in ApcMin/+ mice.
AB  - The Apc(Min/+) mouse has a mutation in the Apc tumor suppressor gene and develops
      intestinal polyps, beginning at 4 wk of age. This mouse develops cachexia by 6
      mo, characterized by significant loss of muscle and fat tissue. The purpose of
      the present study was to determine the role of circulating interleukin-6 (IL-6)
      and the polyp burden for the development of cachexia in Apc(Min/+) mice. At 26 wk
      of age, mice exhibiting severe cachectic symptoms had a 61% decrease in
      gastrocnemius muscle weight, complete loss of epididymal fat, a 10-fold increase
      in circulating IL-6 levels, and an 89% increase in intestinal polyps compared
      with mildly cachectic animals. Apc(Min/+)/IL-6(-/-) mice did not lose
      gastrocnemius muscle mass or epididymal fat pad mass while overall polyp number
      decreased by 32% compared with Apc(Min/+) mice. Plasmid-based IL-6 overexpression
      in Apc(Min/+)/IL-6(-/-) mice led to a decrease in gastrocnemius muscle mass and
      epididymal fat pad mass and increased intestinal polyp burden. IL-6
      overexpression did not induce cachexia in non-tumor-bearing mice. These data
      demonstrate that IL-6 is necessary for the onset of adipose and skeletal muscle
      wasting in the Apc(Min/+) mouse and that circulating IL-6 can regulate Apc(Min/+)
      mouse tumor burden.

PMID- 18056982
TI  - Rapid upregulation of GLUT-4 and MCT-4 expression during 16 h of heavy
      intermittent cycle exercise.
AB  - In this study, we have investigated the hypothesis that an exercise protocol
      designed to repeatedly induce a large dependence on carbohydrate and large
      increases in glycolytic flux rate would result in rapid increases in the
      principal glucose and lactate transporters in working muscle, glucose transporter
      (GLUT)-4 and monocarboxylate transporter (MCT)4, respectively, and in activity of
      hexokinase (Hex), the enzyme used to phosphorylate glucose. Transporter abundance
      and Hex activity were assessed in homogenates by Western blotting and
      quantitative chemiluminescence and fluorometric techniques, respectively, in
      samples of tissue obtained from the vastus lateralis in 12 untrained volunteers
      [peak aerobic power (.VO(2peak)) = 44.3 +/- 2.3 ml.kg(-1).min(-1)] before cycle
      exercise at repetitions 1 (R1), 2 (R2), 9 (R9), and 16 (R16). The 16 repetitions
      of the exercise were performed for 6 min at approximately 90% .VO(2peak), once
      per hour. Compared with R1, GLUT-4 increased (P < 0.05) by 28% at R2 and remained
      elevated (P < 0.05) at R9 and R16. For MCT-4, increases (P < 0.05) of 24% were
      first observed at R9 and persisted at R16. No changes were observed in GLUT-1 and
      MCT-1 or in Hex activity. The approximately 17- to 24-fold increase (P < 0.05) in
      muscle lactate observed at R1 and R2 was reduced (P < 0.05) to an 11-fold
      increase at R9 and R16. It is concluded that an exercise protocol designed to
      strain muscle carbohydrate reserves and to result in large increases in lactic
      acid results in a rapid upregulation of both GLUT-4 and MCT-4.

PMID- 18056983
TI  - AMPA receptors undergo channel arrest in the anoxic turtle cortex.
AB  - Without oxygen, all mammals suffer neuronal injury and excitotoxic cell death
      mediated by overactivation of the glutamatergic N-methyl-D-aspartate receptor
      (NMDAR). The western painted turtle can survive anoxia for months, and
      downregulation of NMDAR activity is thought to be neuroprotective during anoxia.
      NMDAR activity is related to the activity of another glutamate receptor, the
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR). AMPAR
      blockade is neuroprotective against anoxic insult in mammals, but the role of
      AMPARs in the turtle's anoxia tolerance has not been investigated. To determine
      whether AMPAR activity changes during hypoxia or anoxia in the turtle cortex,
      whole cell AMPAR currents, AMPAR-mediated excitatory postsynaptic potentials
      (EPSPs), and excitatory postsynaptic currents (EPSCs) were measured. The effect
      of AMPAR blockade on normoxic and anoxic NMDAR currents was also examined. During
      60 min of normoxia, evoked peak AMPAR currents and the frequencies and amplitudes
      of EPSPs and EPSCs did not change. During anoxic perfusion, evoked AMPAR peak
      currents decreased 59.2 +/- 5.5 and 60.2 +/- 3.5% at 20 and 40 min, respectively.
      EPSP frequency (EPSP(f)) and amplitude decreased 28.7 +/- 6.4% and 13.2 +/- 1.7%,
      respectively, and EPSC(f) and amplitude decreased 50.7 +/- 5.1% and 51.3 +/-
      4.7%, respectively. In contrast, hypoxic (Po(2) = 5%) AMPAR peak currents were
      potentiated 56.6 +/- 20.5 and 54.6 +/- 15.8% at 20 and 40 min, respectively. All
      changes were reversed by reoxygenation. AMPAR currents and EPSPs were abolished
      by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In neurons pretreated with CNQX,
      anoxic NMDAR currents were reversibly depressed by 49.8 +/- 7.9%. These data
      suggest that AMPARs may undergo channel arrest in the anoxic turtle cortex.

PMID- 18056984
TI  - Edemagenic gain and interstitial fluid volume regulation.
AB  - Under physiological conditions, interstitial fluid volume is tightly regulated by
      balancing microvascular filtration and lymphatic return to the central venous
      circulation. Even though microvascular filtration and lymphatic return are
      governed by conservation of mass, their interaction can result in exceedingly
      complex behavior. Without making simplifying assumptions, investigators must
      solve the fluid balance equations numerically, which limits the generality of the
      results. We thus made critical simplifying assumptions to develop a simple
      solution to the standard fluid balance equations that is expressed as an
      algebraic formula. Using a classical approach to describe systems with negative
      feedback, we formulated our solution as a "gain" relating the change in
      interstitial fluid volume to a change in effective microvascular driving
      pressure. The resulting "edemagenic gain" is a function of microvascular
      filtration coefficient (K(f)), effective lymphatic resistance (R(L)), and
      interstitial compliance (C). This formulation suggests two types of gain:
      "multivariate" dependent on C, R(L), and K(f), and "compliance-dominated"
      approximately equal to C. The latter forms a basis of a novel method to estimate
      C without measuring interstitial fluid pressure. Data from ovine experiments
      illustrate how edemagenic gain is altered with pulmonary edema induced by venous
      hypertension, histamine, and endotoxin. Reformulation of the classical equations
      governing fluid balance in terms of edemagenic gain thus yields new insight into
      the factors affecting an organ's susceptibility to edema.

PMID- 18056985
TI  - Adaptation to hypobaric hypoxia involves GABA A receptors in the pons.
AB  - Survival in low-oxygen environments requires adaptation of sympathorespiratory
      control networks located in the brain stem. The molecular mechanisms underlying
      adaptation are unclear. In naive animals, acute hypoxia evokes increases in
      phrenic (respiratory) and splanchnic (sympathetic) nerve activities that persist
      after repeated challenges (long-term facilitation, LTF). In contrast, our studies
      show that conditioning rats to chronic hypobaric hypoxia (CHH), an environment
      characteristic of living at high altitude, diminishes the response to hypoxia and
      attenuates LTF in a time-dependent manner. Phrenic LTF decreases following 7 days
      of CHH, and both sympathetic and phrenic LTF disappear following 14 days of CHH.
      Previous studies demonstrated that GABA is released in the brain stem during
      hypoxia and depresses respiratory activity. Furthermore, the sensitivity of brain
      stem neurons to GABA is increased following prolonged hypoxia. In this study, we
      demonstrate that GABA(A) receptor expression changes along with the CHH-induced
      physiological changes. Expression of the GABA(A) receptor alpha4 subunit mRNA
      increases two-fold in animals conditioned to CHH for 7 days. In addition, de novo
      expression of delta and alpha6, a subunit normally found exclusively in the
      cerebellum, is observed after 14 days. Consistent with these changes, diazepam
      insensitive binding sites, characteristic of GABA(A) receptors containing alpha4
      and alpha6 subunits, increase in the pons. Immunohistochemistry revealed that CHH
      induced GABA(A) receptor subunit expression is localized in regions of
      sympathorespiratory control within the pons. Our findings suggest that a GABA(A)
      receptor mediated-mechanism participates in adaptation of the sympathorespiratory
      system to hypobaric hypoxia.

PMID- 18056986
TI  - Splanchnic sequestration of amino acids in aged rats: in vivo and ex vivo
      experiments using a model of isolated perfused liver.
AB  - Splanchnic sequestration of amino acids (SSAA) is a process observed during aging
      that leads to decreased peripheral amino acid (AA) availability. The mechanisms
      underlying SSAA remain unknown. The aim of the present study was to determine
      whether a high-protein diet could increase nitrogen retention in aged rats by
      saturating SSAA and whether SSAA could be explained by dysregulation of hepatic
      nitrogen metabolism. Adult and aged male Sprague-Dawley rats were housed in
      individual metabolic cages and fed a normal-protein (17% protein) or high-protein
      diet (27%) for 2 wk. Nitrogen balance (NB) was calculated daily. On day 14,
      livers were isolated and perfused for 90 min to study AA and urea fluxes. NB was
      lower in aged rats fed a normal-protein diet than in adults, but a high-protein
      diet restored NB to adult levels. Isolated perfused livers from aged rats showed
      decreased urea production and arginine uptake, together with a release of alanine
      (vs. uptake in adult rats) and a hepatic accumulation of alanine. The in vivo
      data suggest that SSAA is a saturable process that responds to an increase in
      dietary protein content. The hepatic metabolism of AA in aged rats is greatly
      modified, and urea production decreases. This result refutes the hypothesis that
      SSAA is associated with an increase in AA disposal via urea production.

PMID- 18056987
TI  - Pharmacological stimulation of brain carnitine palmitoyl-transferase-1 decreases
      food intake and body weight.
AB  - Inhibition of brain carnitine palmitoyl-transferase-1 (CPT-1) is reported to
      decrease food intake and body weight in rats. Yet, the fatty acid synthase (FAS)
      inhibitor and CPT-1 stimulator C75 produces hypophagia and weight loss when given
      to rodents intracerebroventricularly (icv). Thus roles and relative contributions
      of altered brain CPT-1 activity and fatty acid oxidation in these phenomena
      remain unclarified. We administered compounds that target FAS or CPT-1 to mice by
      single icv bolus and examined acute and prolonged effects on feeding and body
      weight. C75 decreased food intake rapidly and potently at all doses (1-56 nmol)
      and dose dependently inhibited intake on day 1. Dose-dependent weight loss on day
      1 persisted through 4 days of postinjection monitoring. The FAS inhibitor
      cerulenin produced dose-dependent (560 nmol) hypophagia for 1 day, weight loss
      for 2 days, and weight regain to vehicle control by day 3. The CPT-1 inhibitor
      etomoxir (32, 320 nmol) did not alter overall day 1 feeding. However, etomoxir
      attenuated the hypophagia produced by C75, indicating that CPT-1 stimulation is
      important for C75's effect. A novel compound, C89b, was characterized in vitro as
      a selective stimulator of CPT-1 that does not affect fatty acid synthesis. C89b
      (100, 320 nmol) decreased feeding in mice for 3 days and produced persistent
      weight loss for 6 days without producing conditioned taste aversion. Similarly,
      intraperitoneal administration decreased feeding and body weight without
      producing conditioned taste aversion. These results suggest a role for brain CPT
      1 in the regulation of energy balance and implicate CPT-1 stimulation as a
      pharmacological approach to weight loss.

PMID- 18056988
TI  - Animal type 1 cryptochromes. Analysis of the redox state of the flavin cofactor
      by site-directed mutagenesis.
AB  - It has recently been realized that animal cryptochromes (CRYs) fall into two
      broad groups. Type 1 CRYs, the prototype of which is the Drosophila CRY, that is
      known to be a circadian photoreceptor. Type 2 CRYs, the prototypes of which are
      human CRY 1 and CRY 2, are known to function as core clock proteins. The
      mechanism of photosignaling by the Type 1 CRYs is not well understood. We
      recently reported that the flavin cofactor of the Type 1 CRY of the monarch
      butterfly may be in the form of flavin anion radical, FAD(*-), in vivo. Here we
      describe the purification and characterization of wild-type and mutant forms of
      Type 1 CRYs from fruit fly, butterfly, mosquito, and silk moth. Cryptochromes
      from all four sources contain FAD(ox) when purified, and the flavin is readily
      reduced to FAD(*-) by light. Interestingly, mutations that block photoreduction
      in vitro do not affect the photoreceptor activities of these CRYs, but mutations
      that reduce the stability of FAD(*-) in vitro abolish the photoreceptor function
      of Type 1 CRYs in vivo. Collectively, our data provide strong evidence for
      functional similarities of Type 1 CRYs across insect species and further support
      the proposal that FAD(*-) represents the ground state and not the excited state
      of the flavin cofactor in Type 1 CRYs.

PMID- 18056989
TI  - The 44-kDa Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its
      multimerization and drug-resistant activity in human prostate cancer cells.
AB  - We previously showed that the 44-kDa serine/threonine kinase Pim-1 (Pim-1L) can
      protect prostate cancer cells from apoptosis induced by chemotherapeutic drugs
      (Xie, Y., Xu, K., Dai, B., Guo, Z., Jiang, T., Chen, H., and Qiu, Y. (2006)
      Oncogene 25, 70-78). To further explore the mechanisms of Pim-1L-mediated
      resistance to chemotherapeutic drugs in prostate cancer cells, we employed a
      yeast two-hybrid screening to identify cellular proteins that were associated
      with Pim-1L, and we found the ABC transporter BCRP/ABCG2 as one of the potential
      interacting partners of Pim-1L. We also showed that the expression level of Pim
      1L and BCRP was up-regulated in mitoxantrone and docetaxel-resistant prostate
      cancer cell lines. Pim-1L was co-localized with BCRP on the plasma membrane and
      induced phosphorylation of BCRP at threonine 362. Knocking-down Pim-1L expression
      in the drug-resistant prostate cancer cells abolished multimer formation of
      endogenous BCRP and resensitized the resistant cells to chemotherapeutic drugs
      suggesting that BCRP phosphorylation induced by Pim-1L was essential for its
      functionality. This is further corroborated by our finding that the plasma
      membrane localization and drug-resistant activity of BCRP were compromised by
      T362A mutation. Our data suggest that Pim-1L may protect prostate cancer cells
      from apoptosis, at least in part, through regulation of transmembrane drug efflux
      pump. These findings may provide a potential therapeutic approach by disrupting
      Pim-1 signaling to reverse BCRP-mediated multidrug resistance.

PMID- 18056990
TI  - The mitochondrial permeability transition regulates cytochrome c release for
      apoptosis during endoplasmic reticulum stress by remodeling the cristae junction.
AB  - The role of the mitochondrial permeability transition (MPT) in apoptosis and
      necrosis is controversial. Here we show that the MPT regulates the release of
      cytochrome c for apoptosis during endoplasmic reticulum (ER) stress by remodeling
      the cristae junction (CJ). CEM cells, HCT116 colon cancer cells, and murine
      embryo fibroblast cells were treated with the ER stressor thapsigargin (THG),
      which led to cyclophilin D-dependent mitochondrial release of the profusion
      GTPase optic atrophy 1 (OPA1), which controls CJ integrity, and cytochrome c,
      leading to apoptosis. Interference RNA knockdown of Bax blocked OPA1 and
      cytochrome c release after THG treatment but did not prevent the MPT, showing
      that Bax was essential for the release of cytochrome c by MPT. In isolated
      mitochondria, MPT led to OPA1 and cytochrome c release independently of voltage
      dependent anion channel and the outer membrane, indicating that the MPT is an
      inner membrane phenomenon. Last, the MPT was regulated by the electron transport
      chain but not mitochondrial reactive oxygen species, since THG-induced cell death
      was not blocked by antioxidants and did not occur in cells lacking mitochondrial
      DNA. Our results show that the MPT regulates CJ remodeling for cytochrome c
      dependent apoptosis induced by ER stress and that mitochondrial electron
      transport is indispensable for this process.

PMID- 18056991
TI  - Critical role of Val-304 in conformational transitions that allow Ca2+ occlusion
      and phosphoenzyme turnover in the Ca2+ transport ATPase.
AB  - Site-directed mutations were produced in the distal segments of the Ca(2+)-ATPase
      (SERCA) transmembrane region. Mutations of Arg-290 (M3-M4 loop), Lys-958, and Thr
      960 (M9 - M10 loop) had minor effects on ATPase activity and Ca(2+) transport. On
      the other hand, Val-304 (M4) mutations to Ile, Thr, Lys, Ala, or Glu inhibited
      transport by 90-95% while reducing ATP hydrolysis by 83% (Ile, Thr, and Lys), 56%
      (Ala), or 45% (Glu). Val-304 participates in Ca(2+) coordination with its main
      chain carbonyl oxygen, and this function is not expected to be altered by
      mutations of its side chain. In fact, despite turnover inhibition, the Ca(2+)
      concentration dependence of residual ATPase activity remained unchanged in Val
      304 mutants. However, the rates (but not the final levels) of phosphoenzyme
      formation, as well the rates of its hydrolytic cleavage, were reduced in
      proportion to the ATPase activity. Furthermore, with the Val-304 --> Glu mutant,
      which retained the highest residual ATPase activity, it was possible to show that
      occlusion of bound Ca(2+) was also impaired, thereby explaining the stronger
      inhibition of Ca(2+) transport relative to ATPase activity. The effects of Val
      304 mutations on phosphoenzyme turnover are attributed to interference with
      mechanical links that couple movements of transmembrane segments and headpiece
      domains. The effects of thermal activation energy on reaction rates are thereby
      reduced. Furthermore, inadequate occlusion of bound Ca(2+) following utilization
      of ATP in Val-304 side-chain mutations is attributed to inadequate stabilization
      of the Glu-309 side chain and consequent defect of its gating function.

PMID- 18056992
TI  - A critical role for HSP90 in cancer cell invasion involves interaction with the
      extracellular domain of HER-2.
AB  - HSP90 is a ubiquitously expressed molecular chaperone that controls the folding,
      assembly, intracellular disposition, and proteolytic turnover of many proteins,
      most of which are involved in signal transduction processes. Recently, a surface
      form of HSP90 has been identified and associated with cell migration events. In
      this paper, we explore the interaction of surface HSP90 with HER-2, a receptor
      like glycoprotein and member of the ErbB family of receptor tyrosine kinases that
      play central roles in cellular proliferation, differentiation, and migration as
      well as in cancer progress. The involvement of HSP90 in the regulation of HER-2
      has been attributed so far to receptor stabilization via interaction with its
      cytoplasmic kinase domain. Here we present evidence, using glutathione S
      transferase pull-down and transfection assays, for a novel interaction between
      surface HSP90 and the extracellular domain of HER-2. Specific disruption of this
      interaction using mAb 4C5, a function-blocking monoclonal antibody against HSP90,
      inhibits cell invasion accompanied by altered actin dynamics in human breast
      cancer cells under ligand stimulation conditions with heregulin. Additionally,
      disruption of surface HSP90/HER-2 interaction leads to inhibition of heregulin
      induced HER-2-HER-3 heterodimer formation, reduced HER-2 phosphorylation, and
      impaired downstream kinase signaling. Interestingly, this disruption does not
      affect HER-2 internalization. Our data suggest that surface HSP90 is involved in
      heregulin-induced HER-2 activation and signaling, leading to cytoskeletal
      rearrangement, essential for cell invasion.

PMID- 18056993
TI  - Unstructured N terminus of the RNA polymerase II subunit Rpb4 contributes to the
      interaction of Rpb4.Rpb7 subcomplex with the core RNA polymerase II of
      Saccharomyces cerevisiae.
AB  - Two subunits of eukaryotic RNA polymerase II, Rpb7 and Rpb4, form a subcomplex
      that has counterparts in RNA polymerases I and III. Although a medium resolution
      structure has been solved for the 12-subunit RNA polymerase II, the relative
      contributions of the contact regions between the subcomplex and the core
      polymerase and the consequences of disrupting them have not been studied in
      detail. We have identified mutations in the N-terminal ribonucleoprotein-like
      domain of Saccharomyces cerevisiae Rpb7 that affect its role in certain stress
      responses, such as growth at high temperature and sporulation. These mutations
      increase the dependence of Rpb7 on Rpb4 for interaction with the rest of the
      polymerase. Complementation analysis and RNA polymerase pulldown assays reveal
      that the Rpb4.Rbp7 subcomplex associates with the rest of the core RNA polymerase
      II through two crucial interaction points: one at the N-terminal
      ribonucleoprotein-like domain of Rpb7 and the other at the partially ordered N
      terminal region of Rpb4. These findings are in agreement with the crystal
      structure of the 12-subunit polymerase. We show here that the weak interaction
      predicted for the N-terminal region of Rpb4 with Rpb2 in the crystal structure
      actually plays a significant role in interaction of the subcomplex with the core
      in vivo. Our mutant analysis also suggests that Rpb7 plays an essential role in
      the cell through its ability to interact with the rest of the polymerase.

PMID- 18056994
TI  - CYP2E1 substrate inhibition. Mechanistic interpretation through an effector site
      for monocyclic compounds.
AB  - In this study we offer a mechanistic interpretation of the previously known but
      unexplained substrate inhibition observed for CYP2E1. At low substrate
      concentrations, p-nitrophenol (pNP) was rapidly turned over (47 min(-1)) with
      relatively low K(m) (24 microM); nevertheless, at concentrations of >100 microM,
      the rate of pNP oxidation gradually decreased as a second molecule bound to
      CYP2E1 through an effector site (K(ss) = 260 microm), which inhibited activity at
      the catalytic site. 4-Methylpyrazole (4MP) was a potent inhibitor for both sites
      through a mixed inhibition mechanism. The K(i) for the catalytic site was 2.0
      microM. Although we were unable to discriminate whether an EIS or ESI complex
      formed, the respective inhibition constants were far lower than K(ss). Bicyclic
      indazole (IND) inhibited catalysis through a single CYP2E1 site (K(i) = 0.12
      microM). Similarly, 4MP and IND yielded type II binding spectra that reflected
      the association of either two 4MP or one IND molecule(s) to CYP2E1, respectively.
      Based on computational docking studies with a homology model for CYP2E1, the two
      sites for monocyclic molecules, pNP and 4MP, exist within a narrow channel
      connecting the active site to the surface of the enzyme. Because of the presence
      of the heme iron, one site supports catalysis, whereas the other more distal
      effector site binds molecules that can influence the binding orientation and
      egress of molecules for the catalytic site. Although IND did not bind these sites
      simultaneously, the presence of IND at the catalytic site blocked binding at the
      effector site.

PMID- 18056995
TI  - Crystal structure of human kynurenine aminotransferase II.
AB  - Human kynurenine aminotransferase II (hKAT-II) efficiently catalyzes the
      transamination of knunrenine to kynurenic acid (KYNA). KYNA is the only known
      endogenous antagonist of N-methyl-D-aspartate (NMDA) receptors and is also an
      antagonist of 7-nicotinic acetylcholine receptors. Abnormal concentrations of
      brain KYNA have been implicated in the pathogenesis and development of several
      neurological and psychiatric diseases in humans. Consequently, enzymes involved
      in the production of brain KYNA have been considered potential regulatory
      targets. In this article, we report a 2.16 A crystal structure of hKAT-II and a
      1.95 A structure of its complex with kynurenine. The protein architecture of hKAT
      II reveals that it belongs to the fold-type I pyridoxal 5-phosphate (PLP)
      dependent enzymes. In comparison with all subclasses of fold-type I-PLP-dependent
      enzymes, we propose that hKAT-II represents a novel subclass in the fold-type I
      enzymes because of the unique folding of its first 65 N-terminal residues. This
      study provides a molecular basis for future effort in maintaining physiological
      concentrations of KYNA through molecular and biochemical regulation of hKAT-II.

PMID- 18056996
TI  - Crystal structure of human kynurenine aminotransferase II, a drug target for the
      treatment of schizophrenia.
AB  - Kynurenic acid is an endogenous neuroactive compound whose unbalancing is
      involved in the pathogenesis and progression of several neurological diseases.
      Kynurenic acid synthesis in the human brain is sustained by the catalytic
      activity of two kynurenine aminotransferases, hKAT I and hKAT II. A wealth of
      pharmacological data highlight hKAT II as a sensible target for the treatment of
      neuropathological conditions characterized by a kynurenic acid excess, such as
      schizophrenia and cognitive impairment. We have solved the structure of human KAT
      II by means of the single-wavelength anomalous dispersion method at 2.3-A
      resolution. Although closely resembling the classical aminotransferase fold, the
      hKAT II architecture displays unique features. Structural comparison with a
      prototypical aspartate aminotransferase reveals a novel antiparallel strand-loop
      strand motif that forms an unprecedented intersubunit beta-sheet in the
      functional hKAT II dimer. Moreover, the N-terminal regions of hKAT II and
      aspartate aminotransferase appear to have converged to highly similar although 2
      fold symmetry-related conformations, which fulfill the same functional role. A
      detailed structural comparison of hKAT I and hKAT II reveals a larger and more
      aliphatic character to the active site of hKAT II due to the absence of the
      aromatic cage involved in ligand binding in hKAT I. The observed structural
      differences could be exploited for the rational design of highly selective hKAT
      II inhibitors.

PMID- 18056997
TI  - The tuberculosis prodrug isoniazid bound to activating peroxidases.
AB  - Isoniazid (INH, isonicotinic acid hydrazine) is one of only two therapeutic
      agents effective in treating tuberculosis. This prodrug is activated by the heme
      enzyme catalase peroxidase (KatG) endogenous to Mycobacterium tuberculosis but
      the mechanism of activation is poorly understood, in part because the binding
      interaction has not been properly established. The class I peroxidases ascorbate
      peroxidase (APX) and cytochrome c peroxidase (CcP) have active site structures
      very similar to KatG and are also capable of activating isoniazid. We report here
      the first crystal structures of complexes of isoniazid bound to APX and CcP.
      These are the first structures of isoniazid bound to any activating enzymes. The
      structures show that isoniazid binds close to the delta-heme edge in both APX and
      CcP, although the precise binding orientation varies slightly in the two cases. A
      second binding site for INH is found in APX at the gamma-heme edge close to the
      established ascorbate binding site, indicating that the gamma-heme edge can also
      support the binding of aromatic substrates. We also show that in an active site
      mutant of soybean APX (W41A) INH can bind directly to the heme iron to become an
      inhibitor and in a different mode when the distal histidine is replaced by
      alanine (H42A). These structures provide the first unambiguous evidence for the
      location of the isoniazid binding site in the class I peroxidases and provide
      rationalization of isoniazid resistance in naturally occurring KatG mutant
      strains of M. tuberculosis.

PMID- 18056998
TI  - Electrospray ionization mass spectrometry and exogenous heavy isotope-labeled
      lipid species provide detailed information on aminophospholipid acyl chain
      remodeling.
AB  - Mammalian cells maintain the phospholipid compositions of their different
      membranes remarkably constant. Beside de novo synthesis, degradation, and
      intracellular trafficking, acyl chain remodeling plays an important role in
      phospholipid homeostasis. However, many key details of this process remain
      unresolved, largely because of limitations of existing methodologies. Here we
      describe a novel approach that allows one to study metabolism of individual
      phospholipid species in unprecedented detail. Forty different
      phosphatidylethanolamine (PE) or -serine (PS) species with a deuterium-labeled
      head group were synthesized and introduced to BHK21 or HeLa cells using
      cyclodextrin-mediated transfer. Their metabolism was then monitored in detail by
      electrospray ionization mass spectrometry. Atypical PE and PS species were
      rapidly remodeled at both sn1 and sn2 position, yielding a molecular species
      profile similar to that the endogenous PE and PS. In contrast, remodeling of
      exogenous species identical or similar to major endogenous ones was more limited
      and much slower. Major differences in remodeling pathways and kinetics were
      observed between species within a class, as well as between corresponding PE and
      PS species. These data along with those obtained with pharmacological inhibitors
      strongly suggest that multiple lipid class-specific A-type phospholipases and
      acyl transferases are involved in aminophospholipid remodeling. In conclusion,
      the approach described here provides highly detailed information on remodeling of
      exogenously added (amino)glycerophospholipids and should thus be very helpful
      when elucidating the proteins and processes maintaining molecular species
      homeostasis.

PMID- 18056999
TI  - Mechanism of small heat shock protein function in vivo: a knock-in mouse model
      demonstrates that the R49C mutation in alpha A-crystallin enhances protein
      insolubility and cell death.
AB  - alphaA-crystallin (Cryaa/HSPB4) is a small heat shock protein and molecular
      chaperone that prevents nonspecific aggregation of denaturing proteins. Several
      point mutations in the alphaA-crystallin gene cause congenital human cataracts by
      unknown mechanisms. We took a novel approach to investigate the molecular
      mechanism of cataract formation in vivo by creating gene knock-in mice expressing
      the arginine 49 to cysteine mutation (R49C) in alphaA-crystallin (alphaA-R49C).
      This mutation has been linked with autosomal dominant hereditary cataracts in a
      four-generation Caucasian family. Homologous recombination in embryonic stem
      cells was performed using a plasmid containing the C to T transition in exon 1 of
      the cryaa gene. alphaA-R49C heterozygosity led to early cataracts characterized
      by nuclear opacities. Unexpectedly, alphaA-R49C homozygosity led to small eye
      phenotype and severe cataracts at birth. Wild type littermates did not show these
      abnormalities. Lens fiber cells of alphaA-R49C homozygous mice displayed an
      increase in cell death by apoptosis mediated by a 5-fold decrease in
      phosphorylated Bad, an anti-apoptotic protein, but an increase in Bcl-2
      expression. However, proliferation measured by in vivo bromodeoxyuridine labeling
      did not decline. The alphaA-R49C heterozygous and homozygous knock-in lenses
      demonstrated an increase in insoluble alphaA-crystallin and alphaB-crystallin and
      a surprising increase in expression of cytoplasmic gamma-crystallin, whereas no
      changes in beta-crystallin were observed. Co-immunoprecipitation analysis showed
      increased interaction between alphaA-crystallin and lens substrate proteins in
      the heterozygous knock-in lenses. To our knowledge this is the first knock-in
      mouse model for a crystallin mutation causing hereditary human cataract and
      establishes that alphaA-R49C promotes protein insolubility and cell death in
      vivo.

PMID- 18057000
TI  - Molecular evolution of Keap1. Two Keap1 molecules with distinctive intervening
      region structures are conserved among fish.
AB  - Keap1 is a BTB-Kelch-type substrate adaptor protein of the Cul3-dependent
      ubiquitin ligase complex. Keap1 facilitates the degradation of Nrf2, a
      transcription factor regulating the inducible expression of many cytoprotective
      genes. Through comparative genome analyses, we found that amino acid residues
      composing the pocket of Keap1 that interacts with Nrf2 are highly conserved among
      Keap1 orthologs and related proteins in all vertebrates and in certain
      invertebrates, including flies and mosquitoes. The interaction between Nrf2 and
      Keap1 appears to be widely preserved in vertebrates. Similarly, cysteine residues
      corresponding to Cys-273 and Cys-288 in the intervening region of mouse Keap1,
      which are essential for the repression of Nrf2 activity in cultured cells, are
      conserved among Keap1 orthologs in vertebrates and invertebrates, except fish. We
      found that fish have two types of Keap1, Keap1a and Keap1b. To our surprise,
      Keap1a and Keap1b contain the cysteine residue corresponding to Cys-288 and Cys
      273, respectively. In our analysis of zebrafish Keap1a and Keap1b activities,
      both Keap1a and Keap1b were able to facilitate the degradation of Nrf2 protein
      and repress Nrf2-mediated target gene activation. Individual mutation of either
      residual cysteine residue in Keap1a and Keap1b disrupted the ability of Keap1 to
      repress Nrf2, indicating that the presence of either Cys-273 or Cys-288 is
      sufficient for fish Keap1 molecules to fully function. These results provide an
      important insight into the means by which Keap1 cysteines act as sensors of
      electrophiles and oxidants.

PMID- 18057001
TI  - Distinct linkage between post-translational processing and differential secretion
      of progastrin derivatives in endocrine cells.
AB  - Prohormones often undergo extensive cellular processing prior to secretion. These
      post-translational processing events occur in organelles of the constitutive or
      regulated secretory pathway. The aim of this study was to examine the
      relationship between post-translational modifications and the secretory pathways
      taken by peptides derived from progastrin, the prohormone of gastrin, which in
      vivo is secreted by cells of the pyloric glands and stimulates the release of
      gastric acid. Targeting progastrin to compartments of the early secretory pathway
      shows that endoproteolytic processing is initiated in a pre-trans-Golgi network
      compartment of endocrine but not non-endocrine cells. The resulting N-terminal
      fragments of progastrin are secreted via the constitutive pathway, whereas
      endoproteolytically processed C-terminal fragments are secreted via the regulated
      or constitutive-like pathways. C-terminal fragments derived from progastrin
      differ in characteristic manners in levels and patterns of carboxyamidation and
      tyrosine sulfation in accordance with the secretory pathway taken. Point
      mutations introduced into a sorting motif disrupt these patterns, suggesting that
      differences in post-translational modifications are attributable to differential
      intracellular sorting of precursors. The results suggest a two-step sorting
      mechanism for progastrin leading to differential secretion of processed fragments
      via different secretory pathways.

PMID- 18057002
TI  - The differential impact of disulfide bonds and N-linked glycosylation on the
      stability and function of CD14.
AB  - Innate immunity is the first line defense against invading pathogens. During Gram
      negative bacterial infection, the Toll-like receptor 4 and MD-2 complex recognize
      lipopolysaccharide present in the bacterial cell wall. This recognition can be
      enhanced 100-1000-fold by CD14. However, the beneficial role provided by CD14
      becomes detrimental in the context of sepsis and septic shock. An understanding
      of how CD14 functions will therefore benefit treatments targeted at both immune
      suppression and immune enhancement. In the present study, we use site-directed
      mutagenesis to address the role of disulfide bonds and N-linked glycosylation on
      CD14. A differential impact is observed for the five disulfide bonds on CD14
      folding, with the first two (Cys(6)-Cys(17) and Cys(15)-Cys(32)) being
      indispensable, the third and fourth (Cys(168)-Cys(198) and Cys(222)-Cys(253))
      being important, and the last (Cys(287)-Cys(333)) being dispensable. A functional
      role is observed for the first disulfide bond because the C6A substitution
      severely reduces the ability of CD14 to confer lipopolysaccharide responsiveness
      to U373 cells. Two of the four predicted glycosylation sites, asparagines 132 and
      263, are actually involved in N-linked glycosylation, resulting in heterogeneity
      in CD14 molecular weight. Furthermore, glycosylation at Asn(132) plays a role in
      CD14 trafficking and upstream and/or downstream ligand interactions. When mapped
      onto the crystal structure of mouse CD14, the first two disulfide bonds and
      Asn(132) are in close proximity to the initial beta strands of the leucine rich
      repeat domain. Thus, disulfide bonds and N-linked glycosylation in the initial
      beta sheets of the inner concave surface of CD14 are crucial for structure and
      function.

PMID- 18057003
TI  - The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate
      cancer.
AB  - Several reports have recently documented that CXCR7/RDC1 functions as a chemokine
      receptor for SDF-1/CXCL12, which regulates a spectrum of normal and pathological
      processes. In this study, the role of CXCR7/RDC1 in prostate cancer (PCa) was
      explored. Staining of high density tissue microarrays demonstrates that the
      levels of CXCR7/RDC1 expression increase as the tumors become more aggressive. In
      vitro and in vivo studies with PCa cell lines suggest that alterations in
      CXCR7/RDC1 expression are associated with enhanced adhesive and invasive
      activities in addition to a survival advantage. In addition, it was observed that
      CXCR7/RDC1 levels are regulated by CXCR4. Among the potential downstream targets
      of CXCR7/RDC1 are CD44 and cadherin-11, which are likely to contribute to the
      invasiveness of PCa cells. CXCR7/RDC1 also regulates the expression of the
      proangiogenic factors interleukin-8 or vascular endothelial growth factor, which
      are likely to participate in the regulation of tumor angiogenesis. Finally, we
      found that signaling by CXCR7/RDC1 activates AKT pathways. Together, these data
      demonstrate a role for CXCR7/RDC1 in PCa metastasis and progression and suggest
      potential targets for therapeutic intervention.

PMID- 18057004
TI  - MyD88 functions as a negative regulator of TLR3/TRIF-induced corneal inflammation
      by inhibiting activation of c-Jun N-terminal kinase.
AB  - The adaptor molecule MyD88 is necessary for responses to all Toll-like receptors
      except TLR3 and a subset of TLR4 signaling events, which are mediated by the
      adaptor molecule TRIF. To determine the role of TRIF in host inflammatory
      responses, corneal epithelium of C57BL/6, TLR3(-/-), TRIF(-/-), and MyD88(-/-)
      mice was abraded and stimulated with the synthetic TLR3 ligand poly(I:C). We
      found that poly(I:C) induced a pronounced cellular infiltration into the corneal
      stroma, which was TLR3- and TRIF-dependent. Unexpectedly, the inflammatory
      response was exacerbated in MyD88(-/-) mice, with enhanced neutrophil and
      F4/80(+) cell infiltration into the corneal stroma and elevated corneal haze,
      which is an indicator of loss of corneal transparency. To determine whether MyD88
      dependent inhibition of TLR3/TRIF responses is a general phenomenon, we examined
      cytokine production by MyD88(-/-) bone marrow-derived macrophages; however, no
      significant difference was observed between MyD88(+/+) or MyD88(-/-) macrophages.
      In contrast, human corneal epithelial cells (HCECs) transfected with MyD88 small
      interfering RNA had significantly increased (2.5-fold) CCL5/RANTES production
      compared with control HCECs, demonstrating a negative regulatory role for MyD88
      in TLR3/TRIF responses in these cells. Finally, knockdown of MyD88 in HCECs
      resulted in increased phosphorylation of c-Jun N-terminal kinase (JNK), but not
      p38, IRF-3, or NF-kappaB. Consistent with this finding, the JNK inhibitor
      SP600125, but not p38 inhibitor SB203580, ablated this response. Taken together,
      these findings demonstrate a novel JNK-dependent inhibitory role for MyD88 in the
      TLR3/TRIF activation pathway.

PMID- 18057005
TI  - Phosphatidylinositol 3-kinase activation is required for stress protocol-induced
      modification of hippocampal synaptic plasticity.
AB  - Stress dramatically affects the induction of hippocampal synaptic plasticity;
      however, the molecular details of how it does so remain unclear.
      Phosphatidylinositol 3-kinase (PI3K) signaling plays a crucial role in promoting
      neuronal survival and neuroplasticity, but its role, if any, in stress-induced
      alterations of long term potentiation (LTP) and long term depression (LTD) is
      unknown. We found here that inhibitors of PI3K signaling blocked the effects of
      acute restraint-tail shock stress protocol on LTP and LTD. Therefore, the purpose
      of the present study is to explore the signaling events involving PI3K in terms
      of its role in mediating stress protocol-induced alterations of LTP and LTD. We
      found that stress protocol-induced PI3K activation can be blocked by various
      inhibitors, including RU38486 for glucocorticoid receptors, LY294002 for PI3K,
      and dl-2-amino-5-phosphonopentanoic acid for N-methyl-D-aspartate receptors or
      brain-derived neurotrophic factor antisense oligonucleotides. Also,
      immunoblotting analyses revealed that stress protocol induced a profound and
      prolonged phosphorylation of numbers of PI3K downstream effectors, including 3
      phosphoinositide-dependent protein kinase-1, protein kinase B, mammalian target
      of rapamycin (mTOR), p70 S6 kinase, and eukaryotic initiation factor 4B in
      hippocampal CA1 homogenate, which was prevented by the PI3K inhibitor
      pretreatment. More importantly, we found that stress protocol significantly
      increased the protein expression of dendritic scaffolding protein PSD-95
      (postsynaptic density-95), which is known to be involved in LTP and LTD, in an
      mTOR-dependent manner. These results identify a key role of PI3K signaling in
      mediating the stress protocol-induced modification of hippocampal synaptic
      plasticity and further suggest that PI3K may do so by invoking the protein
      expression of PSD-95.

PMID- 18057006
TI  - Vpr.A3A chimera inhibits HIV replication.
AB  - Several APOBEC3 proteins (A3F and A3G), that are cytidine deaminases restrict
      human immunodeficiency virus (HIV) replication in the absence of the viral
      infectivity factor (Vif) protein. However, Vif leads to their degradation and
      counteracts their effects. Another member, A3A, restricts some retrotransposons
      and another virus but not HIV. We reasoned that this failure was due to the lack
      of appropriate targeting. Thus, we fused A3A to another viral protein, Vpr, which
      binds p6 in Gag and is incorporated into viral cores. Indeed, the Vpr.A3A chimera
      but not A3A was found abundantly in the viral core. It also restricted potently
      the replication of HIV and simian immunodeficiency virus in the presence and
      absence of Vif. Because we identified a high frequency of G to A mutations in
      viral cDNAs, this antiviral activity was mediated by DNA editing. Interestingly,
      our fusion protein did not restrict murine leukemia virus, which does not
      incorporate Vpr. Thus, by targeting appropriately a potent single domain cytidine
      deaminase, we rendered HIV and simian immunodeficiency virus restriction
      resistant to Vif.

PMID- 18057007
TI  - Structural basis of mechanochemical coupling in a hexameric molecular motor.
AB  - The P4 protein of bacteriophage phi12 is a hexameric molecular motor closely
      related to superfamily 4 helicases. P4 converts chemical energy from ATP
      hydrolysis into mechanical work, to translocate single-stranded RNA into a viral
      capsid. The molecular basis of mechanochemical coupling, i.e. how small
      approximately 1 A changes in the ATP-binding site are amplified into nanometer
      scale motion along the nucleic acid, is not understood at the atomic level. Here
      we study in atomic detail the mechanochemical coupling using structural and
      biochemical analyses of P4 mutants. We show that a conserved region, consisting
      of superfamily 4 helicase motifs H3 and H4 and loop L2, constitutes the moving
      lever of the motor. The lever tip encompasses an RNA-binding site that moves
      along the mechanical reaction coordinate. The lever is flanked by gamma-phosphate
      sensors (Asn-234 and Ser-252) that report the nucleotide state of neighboring
      subunits and control the lever position. Insertion of an arginine finger (Arg
      279) into the neighboring catalytic site is concomitant with lever movement and
      commences ATP hydrolysis. This ensures cooperative sequential hydrolysis that is
      tightly coupled to mechanical motion. Given the structural conservation, the
      mutated residues may play similar roles in other hexameric helicases and related
      molecular motors.

PMID- 18057008
TI  - Cell surface levels of organellar Na+/H+ exchanger isoform 6 are regulated by
      interaction with RACK1.
AB  - In mammalian cells, four Na(+)/H(+) exchangers (NHE6 - NHE9) are localized to
      intracellular compartments. NHE6 and NHE9 are predominantly localized to sorting
      and recycling endosomes, NHE7 to the trans-Golgi network, and NHE8 to the mid
      trans-Golgi stacks. The unique localization of NHEs may contribute to
      establishing organelle-specific pH values and ion homeostasis in cells.
      Mechanisms underlying the regulation and targeting of organellar NHEs are largely
      unknown. We identified an interaction between NHE9 and RACK1 (receptor for
      activated C kinase 1), a cytoplasmic scaffold protein, by yeast two-hybrid
      screening using the NHE9 C terminus as bait. The NHE9 C terminus is exposed to
      the cytoplasm, verifying that the interaction is topologically possible. The
      binding region was further delineated to the central region of the NHE9 C
      terminus. RACK1 also bound NHE6 and NHE7, but not NHE8, in vitro. Endogenous
      association between NHE6 and RACK1 was confirmed by co-immunoprecipitation and co
      localization in HeLa cells. The luminal pH of the recycling endosome was elevated
      in RACK1 knockdown cells, accompanied by a decrease in the amount of NHE6 on the
      cell surface, although the total level of NHE6 was not significantly altered.
      These results indicate that RACK1 plays a role in regulating the distribution of
      NHE6 between endosomes and the plasma membrane and contributes to maintaining
      luminal pH of the endocytic recycling compartments.

PMID- 18057009
TI  - Nuclear survivin has reduced stability and is not cytoprotective.
AB  - Survivin is an essential mitotic protein that is overexpressed in many cancers,
      and its presence is correlated with increased resistance to radiation and
      chemotherapy. Here we demonstrate that sending survivin into the nucleus
      accelerates its degradation in a cdh1-dependent manner, abolishes the radio
      resistance normally conferred to cells by its overexpression, and prevents
      survivin from inhibiting apoptosis without affecting its mitotic localization.
      Our data suggest that targeting survivin to the nucleus provides an efficient
      means of eliminating it from the cell and may prove a novel strategy in cancer
      treatment, particularly in combination with radiotherapy.

PMID- 18057010
TI  - Cdc42 regulates E-cadherin ubiquitination and degradation through an epidermal
      growth factor receptor to Src-mediated pathway.
AB  - E-cadherins play an essential role in maintaining epithelial polarity by forming
      Ca2+-dependent adherens junctions between epithelial cells. Here, we report that
      Ca2+ depletion induces E-cadherin ubiquitination and lysosomal degradation and
      that Cdc42 plays an important role in regulating this process. We demonstrate
      that Ca2+ depletion induces activation of Cdc42. This in turn up-regulates
      epidermal growth factor receptor (EGFR) signaling to mediate Src activation,
      leading to E-cadherin ubiquitination and lysosomal degradation. Silencing Cdc42
      blocks activation of EGFR and Src induced by Ca2+ depletion, resulting in a
      reduction in E-cadherin degradation. The role of Cdc42 in regulating E-cadherin
      ubiquitination and degradation is underscored by the fact that constitutively
      active Cdc42(F28L) increases the activity of EGFR and Src and significantly
      enhances E-cadherin ubiquitination and lysosomal degradation. Furthermore, we
      found that GTP-dependent binding of Cdc42 to E-cadherin is critical for Cdc42 to
      induce the dissolution of adherens junctions. Our data support a model that
      activation of Cdc42 contributes to mesenchyme-like phenotype by targeting of E
      cadherin for lysosomal degradation.

PMID- 18057011
TI  - Central venous access port-related complications in outpatient chemotherapy for
      colorectal cancer.
AB  - BACKGROUND: The current standard chemotherapy for advanced or metastatic
      colorectal cancer in Japan is FOLFOX or FOLFIRI therapy. Although both therapies
      include continuous infusion of 5-fluorouracil (5-FU), outpatient home
      chemotherapy is possible by placing a central venous access port (CV-port) and
      using a portable disposable pump. The port system has been placed more frequently
      since the approval of FOLFOX. Consequently, more complications involving ports
      and pumps have been encountered. METHODS: At our hospital, 232 patients with
      colorectal cancer underwent outpatient home chemotherapy by placing a CV-port and
      using a portable disposable pump for continuous infusion of 5-FU between 1998 and
      2005. Incidence and contents of complications involving ports and pumps were
      investigated retrospectively. RESULTS: A total of 54 incidents of complications
      involving ports and pumps were identified in 3142 treatments (1.72%) from among
      34 of the 232 patients (14.7%). In 2005, when FOLFOX was introduced, 31 incidents
      occurred in 1903 treatments (1.63%) for 19 of 149 patients (12.8%). Incidents
      involved port placement (n = 6), catheter and port system-related complications
      (n = 15), puncture needle-related complications (n = 3), skin complications
      related to tape fixation (n = 20) and pump-related complications (n = 10). In 10
      patients (4.3%), system-related complications made therapy difficult to continue
      and system exchange was required. CONCLUSIONS: Technical troubles involving ports
      and pumps occurred at a certain rate, and skin incision was required for system
      exchange in some cases. When performing outpatient chemotherapy using ports and
      pumps, thorough prior guidance and double-checking must be implemented, and
      proper countermeasures must be established.

PMID- 18057012
TI  - Prognostic factors affecting the clinical outcome of adenoid cystic carcinoma of
      the head and neck.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) is an uncommon tumor, constituting
      approximately 10% of all head and neck tumors. Classically, ACC has been
      described as a tumor with indolent, but persistent and recurrent, growth and late
      onset of metastases, leading eventually to death. This study assessed the
      prognostic factors affecting the clinical outcome in patients with ACC in the
      head and neck region. METHODS: We performed a retrospective study of 42 patients
      who underwent primary tumor resection or radiotherapy with curative intent and
      evaluated the clinical parameters, treatment and clinical outcomes. RESULTS:
      Forty-two patients (18 males and 24 females with a median age of 65 years)
      received curative treatment. The overall 3- and 5-year survival was 87.4% and
      55.3%, respectively, whereas the 3- and 5-year disease-free survival was 64.3%
      and 36.1%, respectively. Of the 32 patients in whom recurrence could be
      evaluated, 18 (56.3%) developed distant metastases, with the lung (72.2%) being
      the most common site. Perivascular invasion influenced metastasis to the lung
      with borderline significance (P = 0.053). The recurrence rate was higher (P =
      0.045) in patients with high-grade tumor. The status of lymph node metastasis was
      significantly associated with overall survival (P = 0.030). CONCLUSIONS: High
      tumor grade and lymph node involvement were predictive of recurrence and overall
      survival, respectively. Despite aggressive treatment, it seems to be impossible
      to prevent the development of distant metastasis. Therefore, more research is
      needed to identify molecular biomarkers that predict the clinical outcome and to
      develop effective treatment for patients with ACC.

PMID- 18057013
TI  - Prognostic value of carbonic anhydrase IX and Ki-67 expression in squamous cell
      carcinoma of the tongue.
AB  - BACKGROUND: Hypoxia-induced changes may allow tumor cells to survive under
      sustained hypoxic microenvironments resulting in achievement of more aggressive
      phenotypes. The purpose of this study is to determine the prognostic relevance of
      the expression of carbonic anhydrase IX (CA IX), a hypoxia-related protein in
      surgically resected squamous cell carcinoma of the tongue. We also relate CA IX
      to Ki-67 expression representing tumor cell proliferation to provide a prognostic
      model. METHODS: We analysed the expression of CA IX and Ki-67 with
      immunohistochemistry in 60 patients with squamous cell carcinoma of the tongue.
      RESULTS: The percentage of CA IX-positive tumor cells had a wide variation from
      0.0 to 77.5%, and the Ki-67 expression was 1.50-75.1%. High CA IX and Ki-67
      expression (>/=10.0% of tumor cells positively stained with CA IX and Ki-67) was
      associated with a poorer overall survival (P < 0.05). High CA IX and Ki-67
      expression showed shorter disease-free survival (DFS), although they are not
      statistically significant. To make a risk model based on the expression of CA IX
      and Ki-67, we divided the patients into three groups: high risk (high CA IX and
      Ki-67), low risk (low CA IX and Ki-67) and intermediate risk (either high CA IX
      or Ki-67). Being in the high-risk group was found to be an independent prognostic
      factor for overall survival and DFS in multivariate analysis (P < 0.05).
      CONCLUSION: The expression of CA IX and Ki-67 may be useful for predicting
      prognosis in squamous cell carcinoma of the tongue.

PMID- 18057014
TI  - Sarcomatoid carcinoma with a predominant basaloid squamous carcinoma component:
      the first report of an unusual biphasic tumor of the ureter.
AB  - Malignant tumors of the ureter that display biphasic patterns are very rare; they
      include carcinosarcomas, sarcomatoid carcinomas and carcinomas with
      pseudosarcomatous stroma. Although the distinction between carcinosarcomas and
      sarcomatoid carcinomas has been extensively discussed in the past, the recent
      World Health Organization classification of urinary tract tumors (2004) does not
      distinguish the two lesions and use the term sarcomatoid carcinoma to represent
      these biphasic tumors. The epithelial components of previously reported ureteral
      biphasic tumors comprise transitional cell carcinoma, squamous cell carcinoma,
      carcinoma in situ, small cell carcinoma and adenocarcinoma. In this paper, we
      report the first case of sarcomatoid carcinoma of the ureter with a predominant
      basaloid squamous carcinoma component. A 63-year-old man who had developed
      asymptomatic gross hematuria was diagnosed with a right ureteral tumor and
      underwent a right nephroureterectomy. Macroscopic examination of the excised
      tumor revealed a polypoid mass. Histopathologic examination exposed a tumor with
      malignant epithelial and sarcomatous components. The malignant epithelial
      component was predominantly composed of basaloid squamous carcinoma, and the
      sarcomatous component was mostly composed of undifferentiated spindle cells. A
      small focus of a chondrosarcomatous component was present. There were also
      transitional zones between the two components. In addition, the spindle cells of
      the sarcomatous component were partially positive for cytokeratin 7. We believe
      that the findings of this case study will increase the morphological diversity
      used for diagnosing malignant tumors of the ureter.

PMID- 18057015
TI  - A case of superficial hypopharyngeal cancer treated by EMR.

PMID- 18057016
TI  - Comparison of time trends in oesophagus cancer incidence (1973-1997) in East
      Asia, Europe, and the USA, from cancer incidence in five continents Vols IV VIII.

PMID- 18057018
TI  - Bayesian ranking of biochemical system models.
AB  - MOTIVATION: There often are many alternative models of a biochemical system.
      Distinguishing models and finding the most suitable ones is an important
      challenge in Systems Biology, as such model ranking, by experimental evidence,
      will help to judge the support of the working hypotheses forming each model.
      Bayes factors are employed as a measure of evidential preference for one model
      over another. Marginal likelihood is a key component of Bayes factors, however
      computing the marginal likelihood is a difficult problem, as it involves
      integration of nonlinear functions in multidimensional space. There are a number
      of methods available to compute the marginal likelihood approximately. A detailed
      investigation of such methods is required to find ones that perform appropriately
      for biochemical modelling. RESULTS: We assess four methods for estimation of the
      marginal likelihoods required for computing Bayes factors. The Prior Arithmetic
      Mean estimator, the Posterior Harmonic Mean estimator, the Annealed Importance
      Sampling and the Annealing-Melting Integration methods are investigated and
      compared on a typical case study in Systems Biology. This allows us to understand
      the stability of the analysis results and make reliable judgements in uncertain
      context. We investigate the variance of Bayes factor estimates, and highlight the
      stability of the Annealed Importance Sampling and the Annealing-Melting
      Integration methods for the purposes of comparing nonlinear models. AVAILABILITY:
      Models used in this study are available in SBML format as the supplementary
      material to this article.

PMID- 18057019
TI  - Mutual information without the influence of phylogeny or entropy dramatically
      improves residue contact prediction.
AB  - MOTIVATION: Compensating alterations during the evolution of protein families
      give rise to coevolving positions that contain important structural and
      functional information. However, a high background composed of random noise and
      phylogenetic components interferes with the identification of coevolving
      positions. RESULTS: We have developed a rapid, simple and general method based on
      information theory that accurately estimates the level of background mutual
      information for each pair of positions in a given protein family. Removal of this
      background results in a metric, MIp, that correctly identifies substantially more
      coevolving positions in protein families than any existing method. A significant
      fraction of these positions coevolve strongly with one or only a few positions.
      The vast majority of such position pairs are in contact in representative
      structures. The identification of strongly coevolving position pairs can be used
      to impose significant structural limitations and should be an important
      additional constraint for ab initio protein folding. AVAILABILITY: Alignments and
      program files can be found in the Supplementary Information.

PMID- 18057020
TI  - Association studies for untyped markers with TUNA.
AB  - The software package TUNA (Testing UNtyped Alleles) implements a fast and
      efficient algorithm for testing association of genotyped and ungenotyped variants
      in genome-wide case-control studies. TUNA uses Linkage Disequilibrium (LD)
      information from existing comprehensive variation datasets such as HapMap to
      construct databases of frequency predictors using linear combination of haplotype
      frequencies of genotyped SNPs. The predictors are used to estimate untyped allele
      frequencies, and to perform association tests. The methods incorporated in TUNA
      achieve great accuracy in estimation, and the software is computationally
      efficient and does not demand a lot of system memory and CPU resources.
      AVAILABILITY: The software package is available for download from the website:
      http://www.stat.uchicago.edu/~wen/tuna/.

PMID- 18057021
TI  - Assembly reconciliation.
AB  - MOTIVATION: Many genomes are sequenced by a collaboration of several centers, and
      then each center produces an assembly using their own assembly software. The
      collaborators then pick the draft assembly that they judge to be the best and the
      information contained in the other assemblies is usually not used. METHODS: We
      have developed a technique that we call assembly reconciliation that can merge
      draft genome assemblies. It takes one draft assembly, detects apparent errors,
      and, when possible, patches the problem areas using pieces from alternative draft
      assemblies. It also closes gaps in places where one of the alternative assemblies
      has spanned the gap correctly. RESULTS: Using the Assembly Reconciliation
      technique, we produced reconciled assemblies of six Drosophila species in
      collaboration with Agencourt Bioscience and The J. Craig Venter Institute. These
      assemblies are now the official (CAF1) assemblies used for analysis. We also
      produced a reconciled assembly of Rhesus Macaque genome, and this assembly is
      available from our website http://www.genome.umd.edu. AVAILABILITY: The
      reconciliation software is available for download from
      http://www.genome.umd.edu/software.htm

PMID- 18057022
TI  - Differential targeting of nNOS and AQP4 to dystrophin-deficient sarcolemma by
      membrane-directed alpha-dystrobrevin.
AB  - alpha-Dystrobrevin associates with and is a homologue of dystrophin, the protein
      linked to Duchenne and Becker muscular dystrophies. We used a transgenic approach
      to restore alpha-dystrobrevin to the sarcolemma in mice that lack dystrophin (mdx
      mice) to study two interrelated functions: (1) the ability of alpha-dystrobrevin
      to rescue components of the dystrophin complex in the absence of dystrophin and
      (2) the ability of sarcolemmal alpha-dystrobrevin to ameliorate the dystrophic
      phenotype. We generated transgenic mice expressing alpha-dystrobrevin-2a linked
      to a palmitoylation signal sequence and bred them onto the alpha-dystrobrevin
      null and mdx backgrounds. Expression of palmitoylated alpha-dystrobrevin
      prevented the muscular dystrophy observed in the alpha-dystrobrevin-null mice,
      demonstrating that the altered form of alpha-dystrobrevin was functional. On the
      mdx background, the palmitoylated form of alpha-dystrobrevin was expressed on the
      sarcolemma but did not significantly ameliorate the muscular dystrophy phenotype.
      Palmitoylated dystrobrevin restored alpha-syntrophin and aquaporin-4 (AQP4) to
      the mdx sarcolemma but was unable to recruit beta-dystroglycan or the
      sarcoglycans. Despite restoration of sarcolemmal alpha-syntrophin, neuronal
      nitric oxide synthase (nNOS) was not localized to the sarcolemma, suggesting that
      nNOS requires both dystrophin and alpha-syntrophin for correct localization.
      Thus, although nNOS and AQP4 both require interaction with the PDZ domain of
      alpha-syntrophin for sarcolemmal association, their localization is regulated
      differentially.

PMID- 18057023
TI  - Regulation of gene expression during M-G1-phase in fission yeast through Plo1p
      and forkhead transcription factors.
AB  - In fission yeast the expression of several genes during M-G1 phase is controlled
      by binding of the PCB binding factor (PBF) transcription factor complex to Pombe
      cell cycle box (PCB) promoter motifs. Three components of PBF have been
      identified, including two forkhead-like proteins Sep1p and Fkh2p, and a MADS-box
      like protein, Mbx1p. Here, we examine how PBF is controlled and reveal a role for
      the Polo kinase Plo1p. plo1(+) shows genetic interactions with sep1(+), fkh2(+)
      and mbx1(+), and overexpression of a kinase-domain mutant of plo1 abolishes M-G1
      phase transcription. Plo1p binds to and directly phosphorylates Mbx1p, the first
      time a Polo kinase has been shown to phosphorylate a MADS box protein in any
      organism. Fkh2p and Sep1p interact in vivo and in vitro, and Fkh2p, Sep1p and
      Plo1p contact PCB promoters in vivo. However, strikingly, both Fkh2p and Plo1p
      bind to PCB promoters only when PCB-controlled genes are not expressed during S-
      and G2-phase, whereas by contrast Sep1p contacts PCBs coincident with M-G1-phase
      transcription. Thus, Plo1p, Fkh2p and Sep1p control M-G1-phase gene transcription
      through a combination of phosphorylation and cell-cycle-specific DNA binding to
      PCBs.

PMID- 18057024
TI  - Functional diversification of centrins and cell morphological complexity.
AB  - In addition to their key role in the duplication of microtubule organising
      centres (MTOCs), centrins are major constituents of diverse MTOC-associated
      contractile arrays. A centrin partner, Sfi1p, has been characterised in yeast as
      a large protein carrying multiple centrin-binding sites, suggesting a model for
      centrin-mediated Ca2+-induced contractility and for the duplication of MTOCs. In
      vivo validation of this model has been obtained in Paramecium, which possesses an
      extended contractile array - the infraciliary lattice (ICL) - essentially
      composed of centrins and a huge Sfi1p-like protein, PtCenBP1p, which is essential
      for ICL assembly and contractility. The high molecular diversity revealed here by
      the proteomic analysis of the ICL, including ten subfamilies of centrins and two
      subfamilies of Sf1p-like proteins, led us to address the question of the
      functional redundancy, either between the centrin-binding proteins or between the
      centrin subfamilies. We show that all are essential for ICL biogenesis. The two
      centrin-binding protein subfamilies and nine of the centrin subfamilies are ICL
      specific and play a role in its molecular and supramolecular architecture. The
      tenth and most conserved centrin subfamily is present at three cortical locations
      (ICL, basal bodies and contractile vacuole pores) and might play a role in
      coordinating duplication and positioning of cortical organelles.

PMID- 18057026
TI  - Arginine methylation at a glance.

PMID- 18057027
TI  - Advances in fluorescent protein technology.
AB  - Current fluorescent protein (FP) development strategies are focused on fine
      tuning the photophysical properties of blue to yellow variants derived from the
      Aequorea victoria jellyfish green fluorescent protein (GFP) and on the
      development of monomeric FPs from other organisms that emit in the yellow-orange
      to far-red regions of the visible light spectrum. Progress toward these goals has
      been substantial, and near-infrared emitting FPs may loom over the horizon. The
      latest efforts in jellyfish variants have resulted in new and improved monomeric
      BFP, CFP, GFP and YFP variants, and the relentless search for a bright, monomeric
      and fast-maturing red FP has yielded a host of excellent candidates, although
      none is yet optimal for all applications. Meanwhile, photoactivatable FPs are
      emerging as a powerful class of probes for intracellular dynamics and,
      unexpectedly, as useful tools for the development of superresolution microscopy
      applications.

PMID- 18057028
TI  - Nucleotide P2Y1 receptor regulates EGF receptor mitogenic signaling and
      expression in epithelial cells.
AB  - Epidermal growth factor receptor (EGFR) function is transregulated by a variety
      of stimuli, including agonists of certain G-protein-coupled receptors (GPCRs).
      One of the most ubiquitous GPCRs is the P2Y(1) receptor (P2RY1, hereafter
      referred to as P2Y(1)R) for extracellular nucleotides, mainly ADP. Here, we show
      in tumoral HeLa cells and normal FRT epithelial cells that P2Y(1)R broadcasts
      mitogenic signals by transactivating the EGFR. The pathway involves PKC, Src and
      cell surface metalloproteases. Stimulation of P2Y(1)R for as little as 15-60
      minutes triggers mitogenesis, mirroring the half-life of extracellular ADP.
      Apyrase degradation of extracellular nucleotides and drug inhibition of P2Y(1)R,
      both reduced basal cell proliferation of HeLa and FRT cells, but not MDCK cells,
      which do not express P2Y(1)R. Thus, cell-released nucleotides constitute strong
      mitogenic stimuli, which act via P2Y(1)R. Strikingly, MDCK cells ectopically
      expressing P2Y(1)R display a highly proliferative phenotype that depends on EGFR
      activity associated with an increased level of EGFR, thus disclosing a novel
      aspect of GPCR-mediated regulation of EGFR function. These results highlight a
      role of P2Y(1)R in EGFR-dependent epithelial cell proliferation. P2Y(1)R could
      potentially mediate both trophic stimuli of basally released nucleotides and
      first-line mitogenic stimulation upon tissue damage. It could also contribute to
      carcinogenesis and serve as target for antitumor therapies.

PMID- 18057029
TI  - Drosophila Vps35 function is necessary for normal endocytic trafficking and actin
      cytoskeleton organisation.
AB  - To identify novel proteins required for receptor-mediated endocytosis, we have
      developed an RNAi-based screening method in Drosophila S2 cells, based on uptake
      of a scavenger receptor ligand. Some known endocytic proteins are essential for
      endocytosis in this assay, including clathrin and alpha-adaptin; however, other
      proteins important for synaptic vesicle endocytosis are not required. In a small
      screen for novel endocytic proteins, we identified the Drosophila homologue of
      Vps35, a component of the retromer complex, involved in endosome-to-Golgi
      trafficking. Loss of Vps35 inhibits scavenger receptor ligand endocytosis, and
      causes mislocalisation of a number of receptors and endocytic proteins. Vps35 has
      tumour suppressor properties because its loss leads to overproliferation of blood
      cells in larvae. Its loss also causes signalling defects at the neuromuscular
      junction, including upregulation of TGFbeta/BMP signalling and excessive
      formation of synaptic terminals. Vps35 negatively regulates actin polymerisation,
      and genetic interactions suggest that some of the endocytic and signalling
      defects of vps35 mutants are due to this function.

PMID- 18057030
TI  - A dileucine motif in its cytoplasmic domain directs beta-catenin-uncoupled E
      cadherin to the lysosome.
AB  - The E-cadherin-catenin complex regulates Ca(2+)-dependent cell-cell adhesion and
      is localized to the basolateral membrane of polarized epithelial cells.
      Uncoupling beta-catenin from E-cadherin by deletion or substitution mutations
      causes accumulation of these proteins in intracellular compartments, including
      the trans-Golgi network and early endosomes, and degradation in lysosomes.
      Expression of a dominant-negative dynamin did not change the pattern of the
      mutant E-cadherin localization, indicating that the endocytosis of the protein
      from the cell surface does not contribute significantly to the accumulation of
      the protein in the intracellular compartments. Alternatively, E-cadherin lacking
      its entire cytoplasmic domain (tail-less E-cadherin) was detected on the surface
      of cells and targeted to the basolateral membrane. We found that 20 amino acid
      residues within the juxtamembrane region contain the signal responsible for
      intracellular accumulation and the lysosomal targeting of E-cadherin. A dileucine
      motif within this region seems crucial, because substitution of these residues to
      alanines resulted in efficient surface expression of the protein. The tail-less E
      cadherin construct and the dileucine-substitution construct were detected on the
      basolateral membranes. Thus, the dileucine motif of E-cadherin is not required
      for its basolateral targeting.

PMID- 18057031
TI  - Munc18-1 prevents the formation of ectopic SNARE complexes in living cells.
AB  - Membrane trafficking in eukaryotic cells must be strictly regulated both
      temporally and spatially. The assembly at the plasma membrane of the ternary
      SNARE complex, formed between syntaxin1a, SNAP-25 and VAMP, is essential for
      efficient exocytotic membrane fusion. These exocytotic SNAREs are known to be
      highly promiscuous in their interactions with other non-cognate SNAREs. It is
      therefore an important cellular requirement to traffic exocytotic SNARE proteins
      through the endoplasmic reticulum and Golgi complex while avoiding ectopic
      interactions between SNARE proteins. Here, we show that syntaxin1a traffics in an
      inactive form to the plasma membrane, requiring a closed-form interaction, but
      not N-terminal binding, with munc18-1. If syntaxin is permitted to interact with
      SNAP-25, both proteins fail to traffic to the plasma membrane, becoming trapped
      in intracellular compartments. The munc18-1-syntaxin interactions must form
      before syntaxin encounters SNAP-25 in the Golgi complex, preventing the formation
      of intracellular exocytotic SNARE complexes there. Upon delivery to the plasma
      membrane, most SNARE clusters in resting cells do not produce detectable FRET
      between t-SNARE proteins. These observations highlight the crucial role that
      munc18-1 plays in trafficking syntaxin through the secretory pathway.

PMID- 18057032
TI  - Detention of insolvent patients in Burundian hospitals.
AB  - Between February and June 2006, Human Rights Watch and the Association for the
      Promotion of Human Rights and Detained Persons conducted an investigation into
      the detention of insolvent hospital patients in Burundi. Of 11 hospitals visited,
      nine were found to be holding former patients in detention for being unable to
      pay their hospital bills. Thirty-seven detained patients, and key informants in
      government, hospital administration and health services, were interviewed. The
      detention of insolvent hospital patients was described as a routine practice,
      dating from the 1990s. Conditions of detention included overcrowding,
      insufficient food and water, and withholding of further medical treatment.
      Seventy-two per cent of patients interviewed had been detained for 1 month or
      longer at the time of interview. Mechanisms designed to exempt or reimburse the
      health fees of low-income and indigent people failed to protect patients from
      becoming detained. The detention of insolvent patients is a clear violation of
      rights established under international law, including the right not to be
      arbitrarily detained or detained as debtors and the right to accessible health
      care. The abolition of user fees for women giving birth and for small children in
      May 2006 has reduced the number of detained patients, but in June 2006 we visited
      two hospitals and found 77 detained men, older children and women with other
      health problems. Burundi, with the support of the international community, must
      immediately stop the detention of patients and address the urgent financing needs
      of health facilities.

PMID- 18057033
TI  - NICE guidance does not tally with clinical practice--a district general
      experience.

PMID- 18057034
TI  - Hsp90 canalizes developmental perturbation.
AB  - Stochastic processes are intrinsic phenomena that perturb developmental
      processes. However, the canalization process restricts the magnitude of
      perturbation and hence the magnitude of morphological variation during
      development. Heat-shock protein 90 (Hsp90) chaperones are a class of proteins
      stabilizing a network of 'client' proteins that are involved in diverse signal
      transduction pathways affecting development. Here it is reported that a reduction
      of Hsp90 gene dose creates canalization perturbations that affect many aspects of
      Arabidopsis development and results in a plethora of morphological alterations.
      Hence, Hsp90 restricts stochastic phenomena by minimizing perturbations, thereby
      canalizing development. It is also shown that morphogenesis is determined by
      three mutually inter-related parameters: genotype, environment, and time. Hsp90
      is involved in the interaction of these three parameters which ultimately affect
      developmental processes. The amount of phenotypic variation upon the reduction of
      Hsp90 function could be perceived as adaptive and could have an impact on the
      evolutionary process.

PMID- 18057035
TI  - Effects of shoot bending on lateral fate and hydraulics: invariant and changing
      traits across five apple genotypes.
AB  - The aim of this work was to study the variability of physiological responses to
      bending and the relationship with hydraulic conductance of the sap pathway to the
      laterals for five apple genotypes. The study focuses on the fate of the laterals.
      The genetic variability of bending can have two sources: a genetic variability of
      stem geometry which can lead to differences in mechanical state; and a genetic
      variability of sensitivity to bending. Since the aim was to check if some genetic
      variability of sensitivity to bending exists, the genetic variability of shoot
      geometry was taken into account. To do so, bending was controlled by imposing
      different bending intensities using guides of different curvature conferring a
      similar level of deformation to the five genotypes. Bending was done either in
      the proximal zone or in the distal zone of shoots, in June and in the following
      winter, respectively. A Principal Component Analysis comparing upright and bent
      shoots revealed that bending in the proximal zone stimulated vegetative growth of
      buds which would otherwise stay latent. A second Principal Component Analysis
      restricted to bent shoots revealed that bending increased the abortion of
      laterals in the lower face of the shoots. The abortion phenomenon was to the
      detriment of sylleptic laterals or of inflorescence, depending on the genotype.
      There was a strong effect of position around the shoot on within-shoot
      hydraulics. Hydraulic conductance was significantly decreased in the lower face
      of the shoot bent in winter. This result suggested a causal relationship between
      this phenomenon and lateral abortion.

PMID- 18057036
TI  - Transpiration efficiency of a tropical pioneer tree (Ficus insipida) in relation
      to soil fertility.
AB  - The response of whole-plant water-use efficiency, termed transpiration efficiency
      (TE), to variation in soil fertility was assessed in a tropical pioneer tree,
      Ficus insipida Willd. Measurements of stable isotope ratios (delta(13)C,
      delta(18)O, delta(15)N), elemental concentrations (C, N, P), plant growth,
      instantaneous leaf gas exchange, and whole-plant water use were used to analyse
      the mechanisms controlling TE. Plants were grown individually in 19 l pots with
      non-limiting soil moisture. Soil fertility was altered by mixing soil with
      varying proportions of rice husks, and applying a slow release fertilizer. A
      large variation was observed in leaf photosynthetic rate, mean relative growth
      rate (RGR), and TE in response to experimental treatments; these traits were well
      correlated with variation in leaf N concentration. Variation in TE showed a
      strong dependence on the ratio of intercellular to ambient CO(2) mole fractions
      (c(i)/c(a)); both for instantaneous measurements of c(i)/c(a) (R(2)=0.69, P
      <0.0001, n=30), and integrated estimates based on C isotope discrimination
      (R(2)=0.88, P <0.0001, n=30). On the other hand, variations in the leaf-to-air
      humidity gradient, unproductive water loss, and respiratory C use probably played
      only minor roles in modulating TE in the face of variable soil fertility. The
      pronounced variation in TE resulted from a combination of the strong response of
      c(i)/c(a) to leaf N, and inherently high values of c(i)/c(a) for this tropical
      tree species; these two factors conspired to cause a 4-fold variation among
      treatments in (1-c(i)/c(a)), the term that actually modifies TE. Results suggest
      that variation in plant N status could have important implications for the
      coupling between C and water exchange in tropical forest trees.

PMID- 18057037
TI  - Model-assisted analysis of tomato fruit growth in relation to carbon and water
      fluxes.
AB  - This work proposed a model of tomato growth adapted from the Fishman and Genard
      model developed to predict carbon and water accumulation in peach fruit. The main
      adaptations relied on the literature on tomato and mainly concerned: (i) the
      decrease in cell wall extensibility coefficient during fruit development; (ii)
      the increase in the membrane reflection coefficient to solute from 0 to 1, which
      accounted for the switch from symplasmic to apoplasmic phloem unloading, and
      (iii) the negative influence of the initial fruit weight on the maximum rate of
      active carbon uptake based on the assumption of higher competition for carbon
      among cells in large fruits containing more cells. A sensitivity analysis was
      performed and the model was calibrated and evaluated with satisfaction on 17
      experimental datasets obtained under contrasting environmental (temperature, air
      vapour pressure deficit) and plant (plant fruit load and fruit position)
      conditions. Then the model was used to analyse the variations in the main fluxes
      involved in tomato fruit growth and accumulation of carbon in response to virtual
      carbon and water stresses. The conclusions are that this model, integrating
      simple biophysical laws, was able to simulate the complex fruit behaviour in
      response to external or internal factors and thus it may be a powerful tool for
      managing fruit growth and quality.

PMID- 18057038
TI  - Effect of cold acclimation on the photosynthetic performance of two ecotypes of
      Colobanthus quitensis (Kunth) Bartl.
AB  - The effects of cold acclimation of two ecotypes (Antarctic and Andes) of
      Colobanthus quitensis (Kunth) Bartl. Caryophyllaceae on their photosynthetic
      characteristics and performance under high light (HL) were compared. Non
      acclimated plants of the Antarctic ecotype exhibited a higher (34%) maximal rate
      of photosynthesis than the Andes ecotype. In cold-acclimated plants the light
      compensation point was increased. Dark respiration was significantly increased
      during the exposure to 4 degrees C in both ecotypes. Cold-acclimated Antarctic
      plants showed higher Phi(PSII) and qP compared with the Andes ecotype. In
      addition, the Antarctic ecotype exhibited higher heat dissipation (NPQ),
      especially in the cold-acclimated state, which was mainly associated with the
      fast relaxing component of non-photochemical quenching (NPQ(F)). By contrast, the
      Andes ecotype exhibited a lower NPQ(F) and a significant increase in the slowly
      relaxing component (NPQ(s)) at low temperature and HL, indicating higher
      sensitivity to low temperature-induced photoinhibition. Although the xanthophyll
      cycle was fully operational in both ecotypes, cold-acclimated Antarctic plants
      exposed to HL exhibited higher epoxidation state of the xanthophyll cycle
      pigments (EPS) compared with the cold-acclimated Andes ecotype. Thus, the
      photosynthetic apparatus of the Antarctic ecotype operates more efficiently than
      that of the Andes one, under a combination of low temperature and HL. The ecotype
      differences are discussed in relation to the different climatic conditions of the
      two Colobanthus.

PMID- 18057039
TI  - Genome-wide analysis of the UDP-glucose dehydrogenase gene family in Arabidopsis,
      a key enzyme for matrix polysaccharides in cell walls.
AB  - Arabidopsis cell walls contain large amounts of pectins and hemicelluloses, which
      are predominantly synthesized via the common precursor UDP-glucuronic acid. The
      major enzyme for the formation of this nucleotide-sugar is UDP-glucose
      dehydrogenase, catalysing the irreversible oxidation of UDP-glucose into UDP
      glucuronic acid. Four functional gene family members and one pseudogene are
      present in the Arabidopsis genome, and they show distinct tissue-specific
      expression patterns during plant development. The analyses of reporter gene lines
      indicate gene expression of UDP-glucose dehydrogenases in growing tissues. The
      biochemical characterization of the different isoforms shows equal affinities for
      the cofactor NAD(+) ( approximately 40 microM) but variable affinities for the
      substrate UDP-glucose (120-335 microM) and different catalytic constants,
      suggesting a regulatory role for the different isoforms in carbon partitioning
      between cell wall formation and sucrose synthesis as the second major UDP-glucose
      consuming pathway. UDP-glucose dehydrogenase is feedback inhibited by UDP-xylose.
      The relatively (compared with a soybean UDP-glucose dehydrogenase) low affinity
      of the enzymes for the substrate UDP-glucose is paralleled by the weak inhibition
      of the enzymes by UDP-xylose. The four Arabidopsis UDP-glucose dehydrogenase
      isoforms oxidize only UDP-glucose as a substrate. Nucleotide-sugars, which are
      converted by similar enzymes in bacteria, are not accepted as substrates for the
      Arabidopsis enzymes.

PMID- 18057040
TI  - Functional analysis of a RING domain ankyrin repeat protein that is highly
      expressed during flower senescence.
AB  - A gene encoding a RING zinc finger ankyrin repeat protein (MjXB3), a putative E3
      ubiquitin ligase, is highly expressed in petals of senescing four o'clock
      (Mirabilis jalapa) flowers, increasing >40,000-fold during the onset of visible
      senescence. The gene has homologues in many other species, and the Petunia
      homologue is strongly up-regulated in senescing Petunia corollas. Silencing the
      expression of this gene in Petunia, using virus-induced gene silencing, resulted
      in a 2 d extension in flower life. In Mirabilis, a 2 kb promoter region, 5'
      upstream of the MjXB3 gene, was isolated. The promoter sequence included putative
      binding sites for many DNA-binding proteins, including the bZIP, Myb, homeodomain
      leucine zipper (HD-Zip), MADS-box, and WRKY transcription factors. The construct
      containing a 1 kb promoter region immediately upstream of the MjXB3 gene drove
      the strongest expression of the beta-glucuronidase (GUS) reporter gene in a
      transient expression assay. In Petunia, GUS expression under the control of this
      heterologous promoter fragment was specific to senescing flowers. The Mirabilis
      promoter GUS construct was tested in other flower species; while GUS activity in
      carnation petals was high during senescence, no expression was detected in three
      monocotyledonous flowers--daylily (Hemerocallis 'Stella d'Oro'), daffodil
      (Narcissus pseudonarcissus 'King Alfred'), and orchid (Dendrobium 'Emma White').

PMID- 18057041
TI  - Isolation and characterization of four ethylene signal transduction elements in
      plums (Prunus salicina L.).
AB  - Plums are climacteric fruits: their ripening is associated with a burst of
      ethylene production and respiration rate. Stone fruits, including plum, have a
      distinct pattern of growth and development, described as a double sigmoid
      pattern. In order to understand the developmental control of ethylene perception
      in plum, four ethylene perception and signal transduction components (EPSTCs)
      were characterized, including two ETR1-like proteins (Ps-ETR1 and Ps-ERS1), a
      CTR1-like protein, and an ethylene-responsive element-binding factor (ERF). Their
      regulation was studied throughout fruit development and ripening in early and
      late cultivars. Analysis of transcript levels revealed that only Ps-ERF1 and Ps
      ERS1 accumulated immediately after fertilization. Increases in Ps-ETR1 and Ps
      CTR1 transcript levels could not be detected before S3 of fruit development.
      Marked differences associated with the ripening behaviour of early ('Early
      Golden') and late ('Shiro') Japanese plum cultivars were observed. The early
      cultivar showed ripening patterns typical of climacteric fruits accompanied by
      sharp increases of the four transcript levels in an ethylene-dependent manner.
      However, the late cultivar exhibited a suppressed-climacteric pattern, with a
      slight increase in ethylene production related to ripening. The accumulation of
      the Ps-ETR1 (and not Ps-CTR1) mRNA in the late cultivar was ethylene independent.
      Ps-ERS1 mRNA was expressed at low, constant levels, while, Ps-ERF1 remained
      undetectable. The differences between the two plum cultivars in the date and rate
      of ripening in relation to the differences in the accumulation patterns of the
      four mRNAs are discussed.

PMID- 18057042
TI  - The conserved cysteine-rich domain of a tesmin/TSO1-like protein binds zinc in
      vitro and TSO1 is required for both male and female fertility in Arabidopsis
      thaliana.
AB  - Development of reproductive tissue and control of cell division are common
      challenges to all sexually reproducing eukaryotes. The Arabidopsis thaliana TSO1
      gene is involved in both these processes. Mild tso1 mutant alleles influence only
      ovule development, whereas strong alleles have an effect on all floral tissues
      and cause cell division defects. The tso1 mutants described so far carry point
      mutations in a conserved cysteine-rich domain, the CRC domain, but the reason for
      the range of phenotypes observed is poorly understood. In the present study, the
      tesmin/TSO1-like CXC (TCX) proteins are characterized at the biochemical,
      genomic, transcriptomic, and functional level to address this question. It is
      shown that the CRC domain binds zinc, offering an explanation for the severity of
      tso1 alleles where cysteine residues are affected. In addition, the phylogenetic
      and expression analysis of the TCX genes suggested an overlap in function between
      AtTSO1 and the related gene AtTCX2. Their expression ratios indicated that
      pollen, in addition to ovules, would be sensitive to loss of TSO1 function. This
      was confirmed by analysis of novel tso1 T-DNA insertion alleles where the
      development of both pollen and ovules was affected.

PMID- 18057043
TI  - Gene expression associated with increased supercooling capability in xylem
      parenchyma cells of larch (Larix kaempferi).
AB  - Xylem parenchyma cells (XPCs) in larch adapt to subfreezing temperatures by deep
      supercooling, while cortical parenchyma cells (CPCs) undergo extracellular
      freezing. The temperature limits of supercooling in XPCs changed seasonally from 
      30 degrees C during summer to -60 degrees C during winter as measured by freezing
      resistance. Artificial deacclimation of larch twigs collected in winter reduced
      the supercooling capability from -60 degrees C to -30 degrees C. As an approach
      to clarify the mechanisms underlying the change in supercooling capability of
      larch XPCs, genes expressed in association with increased supercooling capability
      were examined. By differential screening and differential display analysis, 30
      genes were found to be expressed in association with increased supercooling
      capability in XPCs. These 30 genes were categorized into several groups according
      to their functions: signal transduction factors, metabolic enzymes, late
      embryogenesis abundant proteins, heat shock proteins, protein synthesis and
      chromatin constructed proteins, defence response proteins, membrane transporters,
      metal-binding proteins, and functionally unknown proteins. All of these genes
      were expressed most abundantly during winter, and their expression was reduced or
      disappeared during summer. The expression of all of the genes was significantly
      reduced or disappeared with deacclimation of winter twigs. Interestingly, all but
      one of the genes were expressed more abundantly in the xylem than in the cortex.
      Eleven of the 30 genes were thought to be novel cold-induced genes. The results
      suggest that change in the supercooling capability of XPCs is associated with
      expression of genes, including genes whose functions have not been identified,
      and also indicate that gene products that have been thought to play a role in
      dehydration tolerance by extracellular freezing also have a function by deep
      supercooling.

PMID- 18057044
TI  - MdERFs, two ethylene-response factors involved in apple fruit ripening.
AB  - Two MdERFs (ethylene-response factors) were isolated from ripening apple
      (Malusxdomestica Borkh. cv. Golden Delicious) fruit. The features of their
      conserved motifs indicated that MdERF1 and MdERF2 belong to group VII and group
      IX categories in Arabidopsis, respectively. MdERF1 was expressed predominantly in
      ripening fruit, although a small degree of expression was also observed in non
      fruit tissues, whereas MdERF2 was expressed exclusively in ripening fruit. The
      increased expression in ripening fruit was repressed by treatment with 1
      methylcyclopropene (1-MCP: a potent antagonist of ethylene receptors), indicating
      that transcription is regulated positively by the ethylene signalling system.
      Indeed, it was a tendency for cultivars with low ethylene production to show
      lower MdERFs expression than those with high ethylene production. On the basis of
      concomitant analyses of the expression of some genes related to ripening, the
      functions of MdERFs and the role of ethylene in the ripening process are
      discussed.

PMID- 18057045
TI  - Identification of variation in adaptively important traits and genome-wide
      analysis of trait-marker associations in Triticum monococcum.
AB  - Einkorn wheat Triticum monococcum (2n=2x=14, A(m)A(m)) is one of the earliest
      domesticated crops. However, it was abandoned for cultivation before the Bronze
      Age and has infrequently been used in wheat breeding. Little is known about the
      genetic variation in adaptively important biological traits in T. monococcum. A
      collection of 30 accessions of diverse geographic origins were characterized for
      phenotypic variation in various agro-morphological traits including grain storage
      proteins and endosperm texture, nucleotide-binding site (NBS) domain profiles of
      resistance (R) genes and resistance gene analogues (RGAs), and germination under
      salt and drought stresses. Forty-six SSR (single sequence repeat) markers from
      bread wheat (T. aestivum, 2n=6x=42, AABBDD) A genome were used to establish trait
      marker associations using linear mixed models. Multiple significant associations
      were identified, some of which were on chromosomal regions containing previously
      known genetic loci. It is concluded that T. monococcum possesses large genetic
      diversity in multiple traits. The findings also indicate that the efficiency of
      association mapping is much higher in T. monococcum than in other plant species.
      The use of T. monococcum as a reference species for wheat functional genomics is
      discussed.

PMID- 18057046
TI  - Sucrose phosphate synthase activity and the co-ordination of carbon partitioning
      during sucrose and amino acid accumulation in desiccation-tolerant leaf material
      of the C4 resurrection plant Sporobolus stapfianus during dehydration.
AB  - Both sucrose and amino acids accumulate in desiccation-tolerant leaf material of
      the C(4) resurrection plant, Sporobolus stapfianus Gandoger (Poaceae). The
      present investigation was aimed at examining sucrose phosphate synthase (SPS)
      activity and various metabolic checkpoints involved in the co-ordination of
      carbon partitioning between these competing pathways during dehydration. In the
      initial phase of dehydration, photosynthesis and starch content declined to
      immeasurable levels, whilst significant increases in hexose sugars, sucrose, and
      amino acids were associated with concomitant significant increases in SPS and
      pyruvate kinase (PK) activities, and maximal activity levels of
      phosphoenolpyruvate carboxylase (PEPCase), NADP-dependent isocitrate
      dehydrogenase (NADP-ICDH), and NADH-dependent glutamate synthase (NADH-GOGAT).
      The next phase of dehydration was characterized by changes in metabolism
      coinciding with net hexose sugar phosphorylation. This phase was characterized by
      a further significant increase in sucrose accumulation, with increased rates of
      net sucrose accumulation and maximum rates of SPS activity measured under both
      saturating and limiting (inhibitory) conditions. SPS protein was also increased.
      The stronger competitive edge of SPS for carbon entering glycolysis during hexose
      phosphorylation was also demonstrated by the further decrease in respiration and
      the simultaneous, significant decline in both PEPCase and PK activities. A
      decreased anabolic demand for 2-oxoglutarate (2OG), which remained constant, was
      shown by the co-ordinated decrease in GOGAT. It is proposed that the further
      increase in amino acids in this phase of dehydration may be in part attributable
      to the breakdown of insoluble proteins.

PMID- 18057047
TI  - Short, direct repeats (SDRs)-mediated post-transcriptional processing of a
      transcription factor gene OsVP1 in rice (Oryza sativa).
AB  - The various degrees of preharvest sprouting occurring in hybrid rice is a
      limiting factor in the propagation and production of hybrid rice seeds. The
      phenotype of sprouted rice is very similar to that of the maize (Zea mays) seed
      specific mutation viviparous 1. VP1 has been shown to be a transcription factor
      essential for seed maturation and dormancy induction. In this study, numerous
      truncated transcripts of OsVP1 resulting from an unusual post-transcriptional
      processing, were detected in four rice (Oryza sativa) cultivars. The observed
      events took place at a region spanning exons 1 to 5, and led to a variety of
      deletions that resulted in the loss of functional domain and frame-shifts with
      premature termination by introducing a stop codon. Various proportions of the
      transcripts expressed in both immature and mature embryos were observed to be
      incorrectly processed and associated with the genetic variation of preharvest
      sprouting rates among various rice varieties. In sprouting-susceptible rice
      cultivars, G46B and HeiB, many more incorrectly processed OsVP1 transcripts were
      expressed in immature than in mature embryos, indicating that the unusual post
      transcriptional processing of the OsVP1 gene was developmentally regulated. In
      addition, comprehensive sequence analyses demonstrated the presence of paired
      short direct repeats (SDRs) at the junctions of the unusual excision sites in
      exons of OsVP1 gene. Site selection for the deletion of exon materials was
      altered along with the genotypes and developmental stages.

PMID- 18057048
TI  - Identification and characterization of carrot HAP factors that form a complex
      with the embryo-specific transcription factor C-LEC1.
AB  - C-LEC1, an orthologue of Arabidopsis LEC1, is thought to be an essential
      transcriptional activator required for normal development during the early and
      late phases of embryogenesis. C-LEC1 is similar in sequence to the HAP3 subunits
      of other organisms. To understand C-LEC1 function better, a cDNA library of
      carrot somatic embryos was screened for factors that form complexes with C-LEC1.
      Two carrot HAP5 homologues and two carrot HAP2 homologues were identified; these
      factors have significant sequence similarity to the conserved regions of HAP5 and
      HAP2, respectively. Some of these proteins form heterotrimeric complexes that
      bind specifically to DNA fragments containing a CCAAT sequence in vitro. The
      results suggest that C-LEC1 is a component of the CCAAT-box-binding factor and
      forms a complex with C-HAP2B and C-HAP5A or C-HAP5B that regulates gene
      expression during carrot embryo development.

PMID- 18057049
TI  - Surgical pleurodesis for Vanderschueren's stage III primary spontaneous
      pneumothorax.
AB  - The aim of the present study was to determine the impact of various pleurodesis
      procedures on post-operative morbidity and late recurrence rate after surgical
      treatment of Vanderschueren's stage III primary spontaneous pneumothorax. Between
      January 2001 and June 2004, 208 consecutive patients (169 male and 39 female;
      mean (range) age 25 (12-39) yrs) were submitted to 220 video-assisted
      thoracoscopic surgical procedures for primary spontaneous pneumothorax. All
      patients underwent apical lung resection; 112 were assigned at random to
      mechanical pleural abrasion (group A) and 108 to apical pleurectomy (group B).
      The two groups of patients showed similar characteristics. No intra- or post
      operative deaths occurred. Post-operative morbidity was 6.25% for group A and
      12.9% for group B; the two groups exhibited a similar persistent post-operative
      air leak rate (5.3% in group A and 5.5% in group B), whereas haemothorax was
      significantly more frequent after apical pleurectomy (eight (7.4%) cases) than
      after pleural abrasion (one (0.9%) case). The mean duration of follow-up was 46
      (24-66) months. Late recurrence occurred in five cases (4.6%) after apical
      pleurectomy, and in seven (6.2%) after mechanical pleural abrasion. Mechanical
      pleural abrasion by video-assisted thoracoscopic surgery is safer than apical
      pleurectomy in the treatment of primary spontaneous pneumothorax. No differences
      in late recurrence rate were observed between the two procedures.

PMID- 18057050
TI  - Inhibition of VEGF blocks TGF-beta1 production through a PI3K/Akt signalling
      pathway.
AB  - Vascular endothelial growth factor (VEGF) is a mediator of airway inflammation
      and remodelling in asthma. Transforming growth factor (TGF)-beta(1) plays pivotal
      roles in diverse biological processes, including tissue remodelling and repair in
      a number of chronic lung diseases. However, there are few studies elucidating the
      interactions between VEGF and TGF-beta(1) in allergic airway disease. A murine
      model of allergic airway disease was used to define the mechanism by which VEGF
      induces subepithelial fibrosis and to investigate a potential relationship
      between VEGF and TGF-beta(1) and the mechanisms by which VEGF signalling
      regulates TGF-beta(1) expression in allergic airway disease. The ovalbumin (OVA)
      inhaled murine model revealed the following typical pathophysiological features
      of allergic airway disease in the lungs: increased numbers of inflammatory cells
      of the airways, airway hyperresponsiveness, increased peribronchial fibrosis, and
      increased levels of VEGF and TGF-beta(1). Administration of VEGF inhibitors
      reduced the pathophysiological signs of allergic airway disease and decreased the
      increased TGF-beta(1) levels and peribronchial fibrosis, including
      phosphoinositide 3-kinase (PI3K) activity after OVA inhalation. In addition, the
      increased TGF-beta(1) levels and collagen deposition after OVA inhalation were
      decreased by administration of PI3K inhibitors. These results suggest that
      inhibition of vascular endothelial growth factor attenuates peribronchial
      fibrosis, at least when mediated by regulation of transforming growth factor
      beta(1) expression through phosphoinositide 3-kinase/Akt pathway in a murine
      model of allergic airway disease.

PMID- 18057051
TI  - Effect of increasing doses of mannitol on mucus clearance in patients with
      bronchiectasis.
AB  - Bronchiectasis is characterised by hypersecretion and impaired clearance of
      mucus. A 400-mg dose of inhaled mannitol improves mucus clearance however, the
      effect of other doses is unknown. A total of 14 patients, aged 63.3+/-5.7 yrs,
      were studied on five visits. Mucus clearance at baseline and with mannitol (160,
      320 and 480 mg) was measured using technetium-99m-sulphur colloid and imaging
      with a gamma camera over 45 min, followed by a further 30 min involving 100
      voluntary coughs. A control study assessed the effect of cough provoked by
      mannitol during the intervention. Whole right lung clearance over 45 min was
      4.7+/-1.2 and 10.6+/-2.6% on baseline and control days, respectively, and
      increased to 16.7+/-4.2, 22.8+/-4.2 and 31+/-4.7% with 160, 320 and 480 mg
      mannitol, respectively. Clearance over 45 min with 480 mg mannitol was greater
      than clearance with 320 and 160 mg. Total clearance over 75 min, after mannitol
      administration and voluntary coughs, was 36.1+/-5.5, 40.9+/-5.6 and 46.0+/-5.2%
      with 160, 320 and 480 mg mannitol, respectively, all significantly different from
      baseline (24.1+/-6.0%) and control (13.1+/-3.0%). Total clearance over 75 min
      with 480 mg mannitol was greater compared with 160 mg. In conclusion, mucus
      clearance increases with increasing doses of mannitol and can be further
      increased by cough in patients with bronchiectasis.

PMID- 18057052
TI  - Endurance shuttle walking test: responsiveness to salmeterol in COPD.
AB  - Few studies have shown that the endurance shuttle walking test (ESWT) is
      responsive to treatment in patients with chronic obstructive pulmonary disease
      (COPD). This exercise test needs to be further investigated because of its
      relevance for activity of daily living. The aim of the present study was to
      evaluate, in patients with COPD, the responsiveness of the ESWT in detecting
      improvement in walking performance after a single dose of salmeterol. In a
      randomised, double-blind, placebo-controlled crossover trial, 20 patients with
      COPD performed two ESWT at 80% of peak capacity 2.5 h after inhaling either a
      placebo or 50 microg of salmeterol. Cardiorespiratory parameters were monitored
      during each walking test. Inspiratory capacities and Borg ratings for dyspnoea
      were obtained every other minute throughout the tests. Compared with placebo,
      salmeterol produced a significant change in lung function and a significant
      improvement in walking performance (mean+/-sd difference in time: 117+/-20 s;
      difference in distance: 160+/-277 m). At isotime (the latest exercise time that
      was reached on both ESWT), a significant reduction in dyspnoea was observed after
      bronchodilation. Bronchodilation with salmeterol reduced dyspnoea during walking
      and improved walking capacity in patients with chronic obstructive pulmonary
      disease. These findings provide further support for the use of the endurance
      shuttle walking test as an evaluative tool in chronic obstructive pulmonary
      disease.

PMID- 18057053
TI  - Indeterminate test results of T-SPOT.TB performed under routine field conditions.
AB  - Interferon-gamma release assays for the diagnosis of tuberculosis (TB) can give
      indeterminate results. The prevalence of indeterminate test results (ITRs) among
      T-SPOT.TB tests was assessed. A retrospective analysis of samples processed in
      2005 was performed. ITRs were assessed by age, sex, immunosuppression, distance
      to the laboratory and season. A subgroup of tests performed for specific
      indications (contact tracing, migrants with positive tuberculin skin test, TB
      suspects and immunosuppression) were analysed separately. Of a total of 1,429
      tests, 49 (3.4%) were indeterminate. ITRs were significantly associated with old
      age (>75 versus 5-75 yrs; odds ratio (OR) 7.97, 95% confidence interval (CI)
      3.968-15.438) and the season during which samples were transported (autumn and
      winter versus spring and summer; OR 3.47, 95% CI 1.753-7.514). The incidence of
      ITR was 302 (2.0%) among TB contacts, 75 (1.6%) among immigrants, 156 (3.0%) in
      TB suspects and 32 (3.0%) among immunosuppressed patients. Sex, young age and
      distance to the laboratory were not associated with the rate of ITR. Of the 13
      tests with ITR that were repeated, 10 gave a clear positive or negative result.
      Indeterminate test results with T-SPOT.TB under routine conditions were
      infrequent and more common in individuals aged >75 yrs than in children and
      younger adults. The incidence of indeterminate test results was low and similar
      among healthy tuberculosis contacts, immigrants with a positive tuberculin skin
      test, tuberculosis suspects and the immunosuppressed. The conditions of
      transportation may influence the incidence of indeterminate test results.

PMID- 18057054
TI  - Nanoparticle-driven DNA damage mimics irradiation-related carcinogenesis
      pathways.
AB  - The epidemiological association between cancer and exposure to ambient air
      pollution particles (particles with a 50% cut-off aerodynamic diameter of 10
      microm (PM(10))) has been related to the ability of PM(10) and its constituent
      nanoparticles (NPs) to cause reactive oxidative species (ROS)-driven DNA damage.
      However, there are no data on the molecular response to these genotoxic effects.
      In order to assess whether PM(10), NP and ROS-driven DNA damage induce
      carcinogenesis pathways, A549 cells were treated with tert-butyl-hyperperoxide
      (Tbh), urban dust (UD), carbon black (CB), nanoparticulate CB (NPCB),
      benzo(a)pyrene (BaP) and NPCB coated with BaP for <or=24 h. Single- and double
      strand breakage of DNA was determined by comet assay; cell cycle status was
      analysed using flow cytometry. Nuclear extracts or acid-extracted histones were
      used for Western blot analysis of p-ser15-p53 (p53 phosphorylated at ser15), p53
      binding protein (53BP) 1, phospho-histone H2A.X (p-H2A.X) and phospho-BRCA1 (p
      BRCA1). UD caused both single- and double-strand DNA breaks, while other tested
      NPs caused only single-strand DNA breaks. NPs significantly altered cell cycle
      kinetics. Tbh enhanced p-H2A.X after 1 and 6 h (2.1- and 2.2-fold, respectively).
      NP increased 53BP1 expression at 1 h (2.4-8.7-fold) and p-BRCA1 at 1-6 h. N
      acetylcysteine blocked NP-driven p-ser15-p53 response. In conclusion,
      nanoparticles and reactive oxidative species induce DNA damage, activating p53
      and proteins related to DNA repair, mimicking irradiation-related carcinogenesis
      pathways.

PMID- 18057055
TI  - Left ventricular diastolic dysfunction in idiopathic pulmonary fibrosis: a tissue
      Doppler echocardiographic [corrected] study.
AB  - It was hypothesised that, apart from right ventricular (RV) dysfunction, patients
      with idiopathic pulmonary fibrosis (IPF) also exhibit left ventricular (LV)
      impairment, which may affect disease progression and prognosis. The aim of the
      present study was to evaluate LV performance in a cohort of IPF patients using
      conventional and tissue Doppler ECG. IPF patients exhibiting mild-to-moderate
      pulmonary arterial hypertension (mean age 65+/-9 yrs; n = 22) and healthy
      individuals (mean age 61+/-6 yrs; n = 22) were studied. Conventional and tissue
      Doppler ECG were used for the evaluation of RV and LV systolic and diastolic
      function. In addition to the expected impairment in RV function, all patients
      showed a characteristic reversal of LV diastolic filling to late diastole
      compared with controls (early diastolic peak filling velocity (E)/late diastolic
      peak filling velocity 0.7+/-0.2 versus 1.5+/-0.1, respectively). Patients with
      IPF also exhibited lower peak myocardial velocities in early diastole (E(m);
      5.7+/-1.1 versus 10.3+/-1.6 cm x s(-1), respectively), higher in late diastole
      (A(m); 8.9+/-1.3 versus 5.5+/-0.8 cm x s(-1), respectively), lower E(m)/A(m)
      ratio (0.6+/-0.1 versus 1.9+/-0.5, respectively) and higher E/E(m) ratio (10.8+/
      3 versus 6+/-0.6, respectively), all indicative of LV diastolic dysfunction.
      Moreover, LV propagation velocity was significantly lower in IPF patients (46+/
      13 versus 83+/-21 cm x s(-1), respectively). Physicians should be aware that
      patients with idiopathic pulmonary fibrosis exhibit early impairment of left
      ventricular diastolic function.

PMID- 18057056
TI  - Value of chest radiography in phenotyping chronic obstructive pulmonary disease.
AB  - The objectives of the present study were to reappraise chest radiography for the
      diagnosis of emphysema, using computed tomography (CT) as the reference standard,
      and to establish whether or not chest radiography is useful for phenotyping
      chronic obstructive pulmonary disease (COPD). Patients (n = 154) who had
      undergone posteroanterior and lateral chest radiography and CT for diagnostic
      purposes were studied. CT data were scored for emphysema using the picture
      grading method. Chest radiographs were examined independently by five raters
      using four criteria for emphysema that had been validated against lung pathology.
      These criteria were then used to assess the prevalence of emphysema in 458 COPD
      patients. Patients with and without evidence of emphysema were compared with
      regard to age, sex, smoking history, body mass index (BMI), forced expiratory
      volume in one second (FEV(1)), diffusing capacity of the lung for carbon monoxide
      (D(L,CO)) and health status. Chest radiography yielded a sensitivity of 90% and a
      specificity of 98% for emphysema. Of the 458 COPD patients, 245 showed
      radiological evidence of emphysema. Emphysemic patients had a significantly lower
      BMI, FEV(1) and D(L,CO), greater restriction of physical activity and worse
      quality of life than nonemphysemic patients. There was no difference across the
      two groups with regard to age, sex or smoking history. Chest radiography is a
      simple means of diagnosing moderate-to-severe emphysema. It is useful in
      phenotyping chronic obstructive pulmonary disease and may aid physicians in their
      choice of treatment.

PMID- 18057057
TI  - Reference equations for lung function screening of healthy never-smoking adults
      aged 18-80 years.
AB  - The need for updated spirometric reference values to be used on European
      populations is widely acknowledged, especially for subjects aged >70 yrs. Their
      reference values are generally based on extrapolations. The aim of the present
      study was to calculate reference values for lung function screening of healthy,
      never-smoking adults aged 18-80 yrs and to compare them with the most widely used
      reference equations. Results of screening spirometry of 8,684 healthy, never
      smoking adults were used to calculate mean values and fifth percentiles of lung
      function variables. The European Community of Coal and Steel (ECCS) reference
      equations underestimate forced expiratory volume in one second (FEV(1)) and
      forced vital capacity (FVC). For example, in 50-yr-old males (height 175 cm),
      lower limits of normal for FEV(1) are underestimated by 198 mL, and for FVC by
      210 mL. In 50-yr-old females (height 165 cm), lower limits of normal for FEV(1)
      are underestimated by 191 mL, and for FVC by 270 mL. The decline of FVC in
      elderly subjects is steeper than predicted by the ECCS. Reference equations
      derived from spirometry data locally collected in a practical setting by well
      trained personnel might be more appropriate for everyday use than generally used
      equations based on data from scientific studies in the distant past.

PMID- 18057058
TI  - Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with
      or without chronic rejection.
AB  - Acid gastro-oesophageal reflux (GOR) and gastric aspiration have been labelled as
      risk factors for chronic rejection bronchiolitis obliterans syndrome (BOS) after
      lung transplantation (LTx). The present study aimed to further characterise GOR
      (both acid and nonacid) and the degree of gastric aspiration in LTx recipients
      both with and without BOS. Impedance-pH recordings were used for GOR detection.
      Pepsin and bile acid levels were measured in bronchoalveolar lavage fluid (BALF).
      A total of 48% of patients had increased GOR, of which 27% had exclusively
      increased nonacid reflux. Cystic fibrosis patients had the highest prevalence of
      GOR. Pepsin was found in BALF of all patients and bile acids in BALF of 50% of
      the patients. Patients with BOS had neither increased GOR nor elevated pepsin in
      BALF. However, 70% of the patients with BOS had bile in BALF compared with 31% of
      stable patients. Proton pump inhibitor (PPI) treatment reduced acid reflux but
      did not affect nonacid reflux. Moreover, pepsin and bile levels in BALF were not
      reduced by PPI. One-half of the lung transplant patients had increased reflux,
      and nonacid reflux was common. Gastric aspiration occurred in most lung
      transplant patients. Pepsin was a more general marker and bile acids a more
      specific marker that might be associated with bronchiolitis obliterans syndrome.
      Proton pump inhibitor treatment did not prevent nonacid reflux and gastric
      aspiration.

PMID- 18057059
TI  - Multidisciplinary interobserver agreement in the diagnosis of idiopathic
      pulmonary fibrosis.
AB  - The purpose of the present study was to evaluate the accuracy of the diagnosis of
      idiopathic pulmonary fibrosis (IPF) by respiratory physicians in six European
      countries, and to calculate the interobserver agreement between high-resolution
      computed tomography reviewers and histology reviewers in IPF diagnosis. The
      diagnosis of usual interstitial pneumonia (UIP) was assessed by a local
      investigator, following the American Thoracic Society/European Respiratory
      Society consensus statement, and confirmed when a minimum of two out of three
      expert reviewers from each expert panel agreed with the diagnosis. The level of
      agreement between readers within each expert panel was calculated by weighted
      kappa. The diagnosis of UIP was confirmed by the expert panels in 87.2% of cases.
      A total of 179 thoracic high-resolution computed tomography scans were
      independently reviewed, and an interobserver agreement of 0.40 was found. Open or
      thoracoscopic lung biopsy was performed in 97 patients, 82 of whom could be
      reviewed by the expert committee. The weighted kappa between histology readers
      was 0.30. It is concluded that, although the level of agreement between the
      readers within each panel was only fair to moderate, the overall accuracy of a
      clinical diagnosis of idiopathic pulmonary fibrosis in expert centres is good
      (87.2%).

PMID- 18057060
TI  - Fibrinogen Aalpha Thr312Ala polymorphism is associated with chronic
      thromboembolic pulmonary hypertension.
AB  - Although chronic thromboembolic pulmonary hypertension (CTEPH) is characterised
      by the persistence of organised thrombus, few pro-thrombotic risk factors have
      been identified in subjects with the disease. The aim of the present study was to
      compare the prevalence of eight functionally relevant haemostatic polymorphisms
      between CTEPH subjects and healthy controls. Genomic DNA was isolated from 214
      CTEPH subjects and 200 healthy controls, and analysed for Factor V Leiden,
      prothrombin guanine (G) to adenine (A) substitution at nucleotide 20210
      (20210G>A), plasminogen activator inhibitor-1 4G/5G, tissue plasminogen activator
      7351 cytosine (C)>thymidine (T), Factor XIII 100G>T, fibrinogen Aalpha
      substitution of threonine with alanine at position 312 (Thr312Ala), fibrinogen
      Bbeta substitution of arginine with lysine at position 448 (Arg448Lys) and
      fibrinogen Bbeta 455G>A polymorphisms. A significant difference was demonstrated
      in fibrinogen Aalpha Thr312Ala genotype and allele frequencies between CTEPH
      subjects and controls. The presence of the alanine allele significantly increased
      the risk of CTEPH. The fibrinogen Aalpha alanine 312 allele alters fibrinogen
      alpha-alpha chain cross-linkage and has previously been associated with both
      increased risk of embolisation and increased resistance to thrombolysis. An
      association between this polymorphism and chronic thromboembolic pulmonary
      hypertension, therefore, supports an embolic aetiology for this disease, and may
      provide a mechanism by which thrombus persists following an acute event.

PMID- 18057061
TI  - Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents.
AB  - During extensive inflammation, neutrophils undergo secondary necrosis causing
      myeloperoxidase (MPO) release that may damage resident lung cells. Recent
      observations suggest that MPO has pro-inflammatory properties, independent of its
      enzymatic activity. The aims of the present study were to characterise MPO
      internalisation by lung epithelial cells and to investigate the effect of MPO on
      oxidative stress, DNA damage and cytokine production by lung epithelial cells.
      Human alveolar and bronchial epithelial cells were stimulated with MPO, with or
      without priming the cells with pro-inflammatory stimuli. MPO protein was detected
      in the cell cytoplasm. Expression of haemoxygenase (HO)-1 and DNA strand breakage
      were determined. The production of interleukin (IL)-8 and -6 were measured.
      Analyses of MPO-stimulated cells demonstrated MPO presence in the cells. HO-1
      expression was increased after MPO stimulation and increased further when cells
      were primed before MPO stimulation. MPO exposure also induced DNA strand
      breakage. Interestingly, MPO inhibited IL-8 production in bronchial, but not
      alveolar epithelium. In conclusion, alveolar and bronchial epithelial cells can
      internalise myeloperoxidase. Stimulation with myeloperoxidase increases
      haemoxygenase-1 expression and DNA strand breakage, suggesting cell damaging
      capacity of myeloperoxidase. In addition, myeloperoxidase inhibited interleukin-8
      production by bronchial epithelial cells, indicating a negative feedback loop for
      neutrophil recruitment.

PMID- 18057062
TI  - Exhaled nitric oxide and asthma control: a longitudinal study in unselected
      patients.
AB  - Controlled studies have shown that monitoring of the exhaled nitric oxide
      fraction (F(eNO)) improves asthma management. However, the studies seldom
      consider the full range of patients seen in clinical practise. In the present
      study, the ability of F(eNO) to reflect asthma control over time is investigated
      in a regular clinical setting, and meaningful F(eNO) cut-off points and changes
      are identified. Answers to the Asthma Control Questionnaire and F(eNO) were
      recorded at least once in 341 unselected asthma patients. The whole population
      and subgroups were considered, i.e. both inhaled corticosteroid (ICS)-naive and
      low or high-to-medium (</= or >500 mug beclomethasone dipropionate
      equivalents.day(-1)) ICS-dose groups. An F(eNO) decrease <40% or increase <30%
      precludes asthma control optimisation or deterioration, respectively (negative
      predictive value 79 and 82%, respectively). In the present study's low-dose
      group, a decrease >40% indicated asthma control optimisation (positive predictive
      value (PPV) 83%). In ICS-naive patients, F(eNO) >35 ppb predicted asthma control
      improvement in response to ICS (PPV 68%). In most cases, forced expiratory volume
      in one second assessments were not useful. In conclusion, in a given patient,
      exhaled nitric oxide fraction was found to be significantly related to asthma
      control over time. The overall ability of exhaled nitric oxide fraction to
      reflect asthma control was reduced in patients using high doses of inhaled
      corticosteroids. Forced expiratory volume in one second had little additional
      value in assessing asthma control.

PMID- 18057063
TI  - Childhood sarcoidosis: long-term follow-up.
AB  - The aim of the present study was to describe clinical features and long-term
      survival in childhood sarcoidosis. In total, 46 ethnic Caucasian Danish children
      (aged <16 yrs, 24 males) with sarcoidosis were identified in 1979-1994. In 33
      (72%) children, diagnosis was verified by histology and, in the remaining 13, by
      clinical and radiological findings. In total, 37 subjects had a follow-up
      examination. Median (range) age at onset of disease was 14 (0.7-15.8) yrs and
      median (range) clinical follow-up was 15 (3-23) yrs after onset of disease. The
      median (range) age at clinical follow-up was 28 (17-30) yrs. At follow-up: 36
      (78%) children recovered completely; 30 (65%) showed complete clinical regression
      at a median (range) 0.7 (0.6-5.9) yrs after onset of disease; two (4%) recovered
      with organ damage (unilateral loss of vision, abnormal chest radiograph); five
      (11%) still had chronic active disease with multiorgan involvement and impaired
      lung function; and three (7%) were deceased, due to central nervous system
      sarcoidosis and acute myeloid leukaemia probably caused by cytostatics. In Danish
      children, sarcoidosis had a favourable prognosis; the majority recovered <6 yrs
      after onset of disease. Some developed chronic active disease and impairment of
      pulmonary function, demanding continuous medical treatment. Prognosis was not
      related to the age at onset of disease. Erythema nodosum was associated with a
      good prognosis, and central nervous system involvement with a poor prognosis.

PMID- 18057064
TI  - Phenotypic characterisation of T-lymphocytes in COPD: abnormal CD4+CD25+
      regulatory T-lymphocyte response to tobacco smoking.
AB  - Tobacco smoking induces an inflammatory response in the lungs of all smokers but,
      for reasons that are still poorly understood, only a proportion of them develop
      chronic obstructive pulmonary disease (COPD). Recent evidence indicates that this
      inflammatory response persists after smoking cessation, suggesting some type of
      auto-perpetuation mechanism similar to that described in autoimmune disorders. T
      lymphocytes (CD4+ and CD8+) have been implicated in the pathogenesis of both COPD
      and several autoimmune processes. A subtype of regulatory CD4+ T-cells expressing
      CD25 (Tregs) plays a critical role in the maintenance of peripheral tolerance and
      the prevention of autoimmunity, but their potential role in COPD has not been
      explored. The present study sought to evaluate maturation (CD45RA/CD45R0) and
      activation markers (CD28) of T-lymphocytes and to explore potential Treg
      abnormalities in COPD. Flow cytometry was used to characterise T-lymphocytes
      obtained from blood and bronchoalveolar lavage fluid (BALF) in 23 patients with
      moderate COPD, 29 smokers with normal lung function and seven never-smokers. The
      main findings were that in BALF: patients with COPD showed higher CD8+CD45RA+ and
      lower CD8+CD45R0+ than smokers with normal lung function; and compared with never
      smokers, smokers with preserved lung function showed a prominent upregulation of
      Tregs that was absent in patients with COPD. These observations indicate a final
      maturation-activation state of CD8+ T-lymphocytes in chronic obstructive
      pulmonary disease and, for the first time, identify a blunted regulatory T-cell
      response to tobacco smoking in these patients, further supporting a potential
      involvement of the acquired immune response in the pathogenesis of the disease.

PMID- 18057065
TI  - Seasonal variation in CO2 efflux of stems and branches of Norway spruce trees.
AB  - BACKGROUND AND AIMS: Stem and branch respiration, important components of total
      forest ecosystem respiration, were measured on Norway spruce (Picea abies) trees
      from May to October in four consecutive years in order (1) to evaluate the
      influence of temperature on woody tissue CO2 efflux with special focus on
      variation in Q10 (change in respiration rate resulting from a 10 degrees C
      increase in temperature) within and between seasons, and (2) to quantify the
      contribution of above-ground woody tissue (stem and branch) respiration to the
      carbon balance of the forest ecosystem. METHODS: Stem and branch CO2 efflux were
      measured, using an IRGA and a closed gas exchange system, 3-4 times per month on
      22-year-old trees under natural conditions. Measurements of ecosystem CO2 fluxes
      were also determined during the whole experiment by using the eddy covariance
      system. Stem and branch temperatures were monitored at 10-min intervals during
      the whole experiment. KEY RESULTS: The temperature of the woody tissue of stems
      and branches explained up to 68% of their CO2 efflux. The mean annual Q10 values
      ranged from 2.20 to 2.32 for stems and from 2.03 to 2.25 for branches. The mean
      annual normalized respiration rate, R10, for stems and branches ranged from 1.71
      to 2.12 micromol CO2 m(-2)s (-1) and from 0.24 to 0.31 micromol CO2 m(-2) s(-1),
      respectively. The annual contribution of stem and branch CO2 efflux to total
      ecosystem respiration were, respectively, 8.9 and 8.1% in 1999, 9.2 and 9.2% in
      2000, 7.6 and 8.6% in 2001, and 8.6 and 7.9% in 2002. Standard deviation for both
      components ranged from 3 to 8% of the mean. CONCLUSIONS: Stem and branch CO2
      efflux varied diurnally and seasonally, and were related to the temperature of
      the woody tissue and to growth. The proportion of CO2 efflux from stems and
      branches is a significant component of the total forest ecosystem respiration,
      approx. 8% over the 4 years, and predictive models must take their contribution
      into account.

PMID- 18057066
TI  - Agalsidase therapy in patients with Fabry disease on renal replacement therapy: a
      nationwide study in Italy.
AB  - BACKGROUND: In Fabry disease, end-stage renal disease (ESRD) and severe
      neurologic and cardiac complications represent the leading causes of late
      morbidity and mortality. A comprehensive Italian nationwide survey study was
      conducted to explore changes in cardiac status and renal allograft function in
      Fabry patients on renal replacement therapy (RRT) and enzyme replacement therapy
      (ERT). METHODS: This study was designed as a cross-sectional survey study with
      prospective follow-up. Of the 34 patients identified via searches in registries,
      31 males and 2 females who received RRT and ERT (agalsidase beta in 30 patients,
      agalsidase alpha in 3) were included. Left ventricular mass index (LVMI),
      interventricular septal thickness at end diastole (IVSD), left ventricular
      posterior wall thickness (LVPWT) and renal allograft function were assessed at
      ERT baseline and subsequently at yearly intervals. RESULTS: The patients in the
      dialysis and transplant groups had been started on dialysis at age 42.0 and 37.1
      years (mean), respectively, and patients in the transplant group received their
      renal allograft at age 39.8 years (mean). The mean age at the start of ERT was
      similar, 44.1 and 44.6 years, respectively. The mean RRT follow-up was 61.1 and
      110.6 months for dialysis and transplant patients, respectively, whereas the ERT
      duration was 45.1 and 48.4 months, respectively. Cardiac parameters increased in
      dialysis patients. In transplant patients, mean LVMI seemed to plateau during
      agalsidase therapy at a lower level as compared to baseline. Decline in renal
      allograft function was relatively mild (-1.92 ml/min/year). Agalsidase therapy
      was well tolerated. Serious ERT-unrelated events occurred more often in the
      dialysis group. CONCLUSIONS: Kidney transplantation should be the standard of
      care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on
      ERT may do better than patients remaining on maintenance dialysis. Larger,
      controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is
      able to change the trajectory of cardiac disease and can preserve graft renal
      function.

PMID- 18057067
TI  - In vivo effect of the natural antioxidant hydroxytyrosol on cyclosporine
      nephrotoxicity in rats.
AB  - BACKGROUND: Cyclosporine A (CsA) is the first-line immunosuppressant used in
      transplant patients and in auto- immune diseases. Nephrotoxicity is the major
      limitation of CsA use. Although the mechanisms of nephrotoxicity have not been
      completely defined, some evidence suggests that reactive oxygen species (ROS)
      play a causal role. The present study was designed to investigate in vivo effects
      of hydroxytyrosol (DOPET), a natural olive oil antioxidant, on oxidative stress,
      renal histology and haemodynamic alterations induced in rats by CsA treatment.
      METHODS: Adult Sprague-Dawley rats were treated i.p. with CsA (15 mg/kg) alone or
      in combination with DOPET (20 mg/kg) for 3 weeks. At the end of the treatment,
      superoxide concentration within the cells of the abdominal aorta and renal artery
      was quantified from the oxidation of dihydroethidium (DHE) using fluorescence
      microscopic imaging analysis. In kidney tissues, lipid peroxidation was measured
      by thiobarbituric acid-reacting substances (TBARS) assay, glutathione level was
      assessed enzymatically and the expression of haem oxygenase-1 (HO-1) gene was
      evaluated by semiquantitative RT-PCR. Renal morphology was studied by classical
      histological techniques, while the glomerular filtration rate (GFR) was estimated
      by inulin clearance. Systemic blood pressure was monitored by the tail method and
      through the catheterization of the carotid artery. RESULTS: CsA administration
      increased superoxide concentration both in the aorta and in the renal artery,
      while DOPET completely prevented this effect. Higher levels of TBARS, a
      significant decrease in GSH and an upregulation of HO-1 mRNA were observed in the
      kidneys of CsA-treated rats. DOPET treatment reversed quantitatively these
      effects. However, CsA-dependent changes in renal histology were only partially
      reversed by DOPET. Finally, CsA induced a severe reduction in GFR and a
      significant increase in both systolic and diastolic blood pressure; the DOPET
      treatment had no significant effect on these haemodynamic alterations.
      CONCLUSION: The reported data indicate that effective DOPET protection from CsA
      induced oxidative stress is associated with a mild effect on histological damages
      and does not affect the altered glomerular function and the hypertension, thus
      indicating that kidney injury by CsA is only in part dependent on oxidative
      stress.

PMID- 18057068
TI  - Geriatric comorbidities, such as falls, confer an independent mortality risk to
      elderly dialysis patients.
AB  - BACKGROUND: As the number of patients aged >/=65 years starting haemodialysis
      (HD) continues to increase, more patients are at risk of falls, functional
      decline and cognitive impairment. In an earlier prospective cohort study, we
      showed that 44% of elderly HD patients had more than one fall within a 1-year
      period. The objective of this study was to assess whether falls remained
      predictive of increased mortality risk even after controlling for age,
      comorbidity, dialysis vintage and laboratory variables. METHODS: Using a
      prospective, cohort study design, patients aged >/=65 years and on chronic HD
      during the period April 2002-2003 were recruited. Patients were followed
      biweekly, and falls occurring within the first year were recorded. Outcome data
      were collected until death, study end (30 December 2006), transplantation or
      transfer to another dialysis centre. RESULTS: A total of 162 patients were
      followed for a median of 32.7 months (quartiles 14-57). In a univariate Cox model
      with a time-dependent variable for falls status, survival was worse amongst
      fallers compared to non-fallers (HR 2.13, 95% CI 1.32-3.45; P = 0.002). After
      adjustment for age, dialysis vintage, comorbidity and laboratory variables, falls
      were a significant predictor of mortality (HR 1.78, 95% CI 1.07-2.98, P = 0.03).
      Exclusion of falls associated with concurrent illnesses did not alter the results
      (HR 1.63, CI 1.02-2.28 P = 0.05). CONCLUSIONS: We conclude that the occurrence of
      more than one accidental fall in a community-dwelling HD patient aged >/=65 years
      is associated with an independent increased risk of death. As fall interventions
      are effective, screening HD patients for falls may be a simple measure of
      clinical importance.

PMID- 18057069
TI  - A genome-wide association study of sporadic ALS in a homogenous Irish population.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by progressive limb or bulbar weakness. Efforts to elucidate the
      disease-associated loci have to date produced conflicting results. One strategy
      to improve power in genome-wide studies is to genotype a genetically homogenous
      population. Such a population exhibits extended linkage disequilibrium (LD) and
      lower allelic heterogeneity to facilitate disease gene mapping. We sought to
      identify associated variants for ALS in the Irish, a stable population of
      relatively homogenous genetic background, and to replicate these findings in
      larger genetically out-bred populations. We conducted a genome-wide association
      study in 432 Irish individuals using Illumina HumanHap 550K single nucleotide
      polymorphism chips. We demonstrated extended LD and increased homogeneity in the
      Irish sample when compared to an out-bred population of mixed European ancestry.
      The Irish scan identified 35 loci associated with P-values below 0.0001. For
      replication, we identified seven chromosomal regions commonly associated in a
      joint analysis of genome-wide data on 958 ALS cases and 932 controls from Ireland
      and the previously published datasets from the US and The Netherlands. When
      pooled, the strongest association was a variant in the gene encoding DPP6, a
      component of type A neuronal transmembrane potassium channels. Further
      confirmation of the candidate loci is warranted in additional genome-wide
      datasets. We have made our individual genotyping data publicly available,
      contributing to a powerful world-wide resource to refine our understanding of the
      genetics of sporadic ALS.

PMID- 18057071
TI  - The effect of antibiotics on methicillin-resistant Staphylococcus aureus.
AB  - Antimicrobial drugs encourage the overgrowth of organisms resistant to the agents
      used. Acquisition and subsequent overgrowth of methicillin-resistant
      Staphylococcus aureus (MRSA) are particularly associated with beta-lactam
      antibiotics and quinolones. These drugs allow rapid proliferation of an organism
      that might have been merely colonizing the skin, leading to clinical infection,
      treatment difficulties and potential transmission to others. In addition, there
      is increasing evidence that inappropriate antibiotics not only encourage
      overgrowth with MRSA but may also enhance pathogenicity. Such virulence is not
      necessarily due to simple expansion of MRSA across skin and mucosal surfaces;
      there appear to be molecular changes that facilitate mechanisms such as quorum
      sensing, adhesion, phage mobilization, exotoxin production, intracellular
      persistence and biofilm formation, all of which contribute towards more severe
      infection. This review examines the association between MRSA and certain classes
      of antibiotics and explores the molecular mechanisms underlying a perceived
      increase in virulence following inappropriate therapy. It is possible that
      empirical prescribing has a significant impact on the management of MRSA
      infections and ultimately patient outcome. It is time to challenge the
      prescribers' right to prescribe what they like, when they like, for patients at
      risk of MRSA.

PMID- 18057072
TI  - Extensible open source content management systems and frameworks: a solution for
      many needs of a bioinformatics group.
AB  - A common challenge for bioinformaticians, in either academic or industry
      laboratory environments, is providing informatic solutions via the Internet or
      through a web browser. Recently, the open source community began developing tools
      for building and maintaining web applications for many disciplines. These content
      management systems (CMS) provide many of the basic needs of an informatics group,
      whether in a small company, a group within a larger organisation or an academic
      laboratory. These tools aid in managing software development, website
      development, document development, course development, datasets, collaborations
      and customers. Since many of these tools are extensible, they can be developed to
      support other research-specific activities, such as handling large biomedical
      datasets or deploying bioanalytic tools. In this review of open source website
      management tools, the basic features of content management systems are discussed
      along with commonly used open source software. Additionally, some examples of
      their use in biomedical research are given.

PMID- 18057073
TI  - An overview of image-processing methods for Affymetrix GeneChips.
AB  - We present an overview of image-processing methods for Affymetrix GeneChips. All
      GeneChips are affected to some extent by spatially coherent defects and image
      processing has a number of potential impacts on the downstream analysis of
      GeneChip data. Fortunately, there are now a number of robust and accurate
      algorithms, which identify the most disabling defects. One group of algorithms
      concentrate on the transformation from the original hybridisation DAT image to
      the representative CEL file. Another set uses dedicated pattern recognition
      routines to detect different types of hybridisation defect in replicates. A third
      type exploits the information provided by public repositories of GeneChips (such
      as GEO). The use of these algorithms improves the sensitivity of GeneChips, and
      should be a prerequisite for studies in which there are only few probes per
      relevant biological signal, such as exon arrays and SNP chips.

PMID- 18057074
TI  - Unravelling Bolero: progressive aphasia, transmodal creativity and the right
      posterior neocortex.
AB  - Most neurological lesion studies emphasize performance deficits that result from
      focal brain injury. Here, we describe striking gains of function in a patient
      with primary progressive aphasia, a degenerative disease of the human language
      network. During the decade before her language deficits arose, Anne Adams (AA), a
      lifelong scientist, developed an intense drive to produce visual art. Paintings
      from AA's artistic peak revealed her capacity to create expressive transmodal
      art, such as renderings of music in paint, which may have reflected an increased
      subjective relatedness among internal perceptual and conceptual images. AA became
      fascinated with Maurice Ravel, the French composer who also suffered from a
      progressive aphasia, and painted his best-known work, 'Bolero', by translating
      its musical elements into visual form. Later paintings, achieved when AA was
      nearly mute, moved towards increasing photographic realism, perhaps because
      visual representations came to dominate AA's mental landscape during this phase
      of her illness. Neuroimaging analyses revealed that, despite severe degeneration
      of left inferior frontal-insular, temporal and striatal regions, AA showed
      increased grey matter volume and hyperperfusion in right posterior neocortical
      areas implicated in heteromodal and polysensory integration. The findings suggest
      that structural and functional enhancements in non-dominant posterior neocortex
      may give rise to specific forms of visual creativity that can be liberated by
      dominant inferior frontal cortex injury.

PMID- 18057075
TI  - Total cavo-pulmonary connection without foreign material for asplenic heart
      associated with partial anomalous pulmonary venous connection.
AB  - The presented case was a 3-year-old boy diagnosed with asplenia (SLL), double
      outlet right ventricle, pulmonary stenosis, atrioventricular septal defect,
      hypoplastic left ventricle and partial anomalous pulmonary venous connection to
      the superior vena cava. Partial anomalous pulmonary venous connection was
      repaired by translocation of pulmonary artery to avoid pulmonary venous
      obstruction when Glenn anastomosis was performed. Total cavo-pulmonary connection
      was established by re-routing the inferior vena cava to pulmonary artery using
      the atrial septal remnant and the left atrium free wall flap.

PMID- 18057076
TI  - Papillary muscle sling and overlapping cardiac volume reduction with aortic valve
      replacement for valvular cardiomyopathy.
AB  - A 63-year-old male was admitted to our hospital because of severe aortic
      regurgitation. The left ventricle was extremely dilated and mild functional
      mitral regurgitation was detected because of outward displacement of papillary
      muscles. We used a papillary muscle sling with aortic valve replacement to
      correct the widened distance between the papillary muscles. A papillary muscle
      sling when used for reducing tethering at the mitral valve also reduces the
      posterior left ventricular volume. As well, a transmural longitudinal incision
      along the left anterior descending artery in the left ventricular free wall was
      sutured by an overlapping method to reduce the anterior left ventricular volume.
      The combination of papillary muscle sling and the overlapping method does not
      need any resection of the cardiac muscle and so would be beneficial for end-stage
      valvular cardiomyopathy.

PMID- 18057077
TI  - Simultaneous multi-vessel coronary artery bypass grafting, ischemic mitral
      regurgitation repair and descending aortic aneurysm replacement: analysis of
      technical points.
AB  - The combination of coronary artery disease and its complications (ischemic mitral
      regurgitation etc.) with the aneurysm of the descending thoracic aorta is not a
      rare case. The single-stage correction of coronary/intracardiac/aortic lesions
      may be considered as a way of managing the combined patients. Simultaneous multi
      vessel coronary artery bypass grafting, suture mitral annuloplasty and descending
      aortic aneurysm replacement with synthetic prosthesis is described. The operation
      was performed through the left thoracotomy with cardiopulmonary bypass
      established by the cannulation of the ascending aorta and of the right atrial
      appendage. Ventricular fibrillation and no clamping of the ascending aorta were
      used. The circulatory arrest was induced for the construction of the proximal
      anastomosis between the descending aorta and the synthetic prosthesis. No
      complications related to the operation were diagnosed for the 14-month follow-up.
      Several technical points seem optimal for the combined procedure: (1)
      Minimization of manipulations on the ascending aorta (using of pedicled left
      internal thoracic artery; construction of the proximal anastomoses with synthetic
      aortic prosthesis; unclamped ascending aorta). (2) Revascularization of all
      coronary areas and correction of intracardiac lesions through the left
      thoracotomy. Individual planning of the procedural technical points for every
      patient may provide a safe feasibility of the combined procedure.

PMID- 18057078
TI  - Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a
      detailed analysis of gene networks and clinical phenotypes.
AB  - AIM: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem
      disease, the pathogenesis of which remains undetermined. The authors have
      recently reported a study of gene expression that identified differential
      expression of 88 human genes in patients with CFS/ME. Clustering of quantitative
      PCR (qPCR) data from patients with CFS/ME revealed seven distinct subtypes with
      distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical
      phenotypes and severity. METHODS: In this study, for each CFS/ME subtype, those
      genes whose expression differed significantly from that of normal blood donors
      were identified, and then gene interactions, disease associations and molecular
      and cellular functions of those gene sets were determined. Genomic analysis was
      then related to clinical data for each CFS/ME subtype. RESULTS: Genomic analysis
      revealed some common (neurological, haematological, cancer) and some distinct
      (metabolic, endocrine, cardiovascular, immunological, inflammatory) disease
      associations among the subtypes. Subtypes 1, 2 and 7 were the most severe, and
      subtype 3 was the mildest. Clinical features of each subtype were as follows:
      subtype 1 (cognitive, musculoskeletal, sleep, anxiety/depression); subtype 2
      (musculoskeletal, pain, anxiety/depression); subtype 3 (mild); subtype 4
      (cognitive); subtype 5 (musculoskeletal, gastrointestinal); subtype 6
      (postexertional); subtype 7 (pain, infectious, musculoskeletal, sleep,
      neurological, gastrointestinal, neurocognitive, anxiety/depression). CONCLUSION:
      It was particularly interesting that in the seven genomically derived subtypes
      there were distinct clinical syndromes, and that those which were most severe
      were also those with anxiety/depression, as would be expected in a disease with a
      biological basis.

PMID- 18057080
TI  - Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST) of ciprofloxacin
      resistant isolates of Pretoria, South Africa.
AB  - Gonococcal isolates resistant to ciprofloxacin collected from 2004 to 2005, in
      the Pretoria region, were characterised using Neisseria gonorrhoeae multi-antigen
      sequence typing (NG-MAST). The isolates were obtained from men presenting with
      urethritis to primary healthcare clinics and general practitioners. All isolates
      were tested for susceptibility to ciprofloxacin by Etest, disc diffusion and agar
      dilution methods. Sequence-based typing, directed at the por and tbpB genes, and
      compared with international isolates using the NG-MAST database on the internet,
      was done for 18 isolates (10 ciprofloxacin-resistant isolates and 8 susceptible
      controls). There was one cluster (four isolates) of known sequence type (ST)
      similar to the pattern seen among strains from Scotland, England, and Durban,
      South Africa. Two other known STs were identified, while the remaining STs were
      unique.

PMID- 18057079
TI  - Detection of plasmid-mediated AmpC in Escherichia coli, Klebsiella pneumoniae and
      Proteus mirabilis.
AB  - AIMS: This study investigated the prevalence of plasmid-mediated AmpC production
      in selected clinical isolates of Escherichia coli, Klebsiella species and Proteus
      mirabilis, and compared the results of boronic acid disc screening with
      conventional susceptibility testing for the detection of AmpC-positive isolates.
      METHODS: E coli, Klebsiella species and P mirabilis with reduced susceptibility
      to amoxycillin-clavulanate, cefuroxime and cephalexin, but without phenotypic
      evidence of extended-spectrum beta-lactamases were screened for AmpC activity
      using enzyme-extraction methods. The presence of plasmid-mediated ampC was
      determined by multiplex PCR. Antibiotic susceptibilities were determined using
      both disc and dilution-based methods. A disc-based screening method for detection
      of AmpC-producing strains was evaluated using boronic acid as an inhibitor of
      AmpC, and cefoxitin as the antibiotic substrate. RESULTS: Plasmid-mediated ampC
      was present in 26% of study isolates, with CMY-like enzymes detected
      predominantly in E coli and DHA-like enzymes predominantly in Klebsiella
      pneumoniae. Current susceptibility methods failed to detect a significant
      proportion of plasmid-mediated AmpC-producing isolates, with 33% of such strains
      interpreted as susceptible to third-generation cephalosporins using current
      Clinical Laboratory Standards Institute breakpoints. The boronic acid disc method
      showed sensitivity and specificity of 90% and 98% respectively in detecting AmpC
      positive isolates. CONCLUSION: The prevalence of plasmid-mediated ampC was high
      in the study population, and may be missed by conventional susceptibility testing
      methods. Inhibitor-based screening methods would improve detection of this
      emerging resistance phenotype.

PMID- 18057081
TI  - Molecular characterisation of a common SDHB deletion in paraganglioma patients.
AB  - BACKGROUND: Hereditary susceptibility to familial paraganglioma syndromes is
      mainly due to mutations in one of six genes, including three of the four genes
      encoding the subunits of the mitochondrial succinate dehydrogenase complex II.
      Although prevalence, penetrance and clinical characteristics of patients carrying
      point mutations affecting the genes encoding succinate dehydrogenase have been
      well studied, little is known regarding these clinical features in patients with
      gross deletions. Recently, we found two unrelated Spanish families carrying the
      previously reported SDHB exon 1 deletion, and suggested that this chromosomal
      region could be a hotspot deletion area. METHODS: We present the molecular
      characterisation of this apparently prevalent mutation in three new families, and
      discuss whether this recurrent mutation is due either to the presence of a
      founder effect or to a hotspot. RESULTS: The breakpoint analysis showed that all
      Iberian Peninsular families described harbour the same exon 1 deletion, and that
      a different breakpoint junction segregates in an affected French pedigree.
      CONCLUSIONS: After haplotyping the SDHB region, we concluded that the deletion
      detected in Iberian Peninsular people is probably due to a founder effect.
      Regarding the clinical characteristics of patients with this alteration, it seems
      that the presence of gross deletions rather than point mutations is more likely
      related to abdominal presentations and younger age at onset. Moreover, we found
      for the first time a patient with neuroblastoma and a germline SDHB deletion, but
      it seems that this paediatric neoplasia in a pheochromocytoma family is not a key
      component of this disease.

PMID- 18057082
TI  - A patient with vertebral, cognitive and behavioural abnormalities and a de novo
      deletion of NRXN1alpha.
AB  - The authors report a patient with mild mental retardation, autistic features,
      multiple vertebral malformations, and an unusual facial appearance who carries a
      de novo submicroscopic deletion of chromosome 2p16.3. The patient's deletion is
      approximately 320 kb in size and includes only the part of the NRXN1 gene that
      codes for the neurexin1alpha promoter and initial coding exons. The more
      downstream neurexin1beta promoter and the region surrounding it are intact.
      Neurexin1beta has been associated with autism in several recent studies, but this
      is the first reported patient with loss of only neurexin1alpha and not of
      neurexin1beta. These findings suggest that neurexin1alpha function in correct
      dosage is necessary for normal neurological development.

PMID- 18057083
TI  - A low symptomatic form of neurodegeneration in younger carriers of the FMR1
      premutation, manifesting typical radiological changes.
AB  - Fragile X-associated tremor/ataxia (FXTAS) is a late onset disorder caused by a
      premutation in the FMR1 gene, in which neurological symptoms are associated with
      white matter (wm) changes, especially within the middle cerebellar peduncles (MCP
      sign), seen on magnetic resonance images (MRIs). We report a discrepancy between
      obvious radiological presentations and minimal clinical involvement in two
      younger male premutation carriers. These carriers, aged 52 and 39 years, showed
      distinct MCP sign, but reported no neurological symptoms. If this discrepancy
      represents the initial stage of FXTAS, our findings suggest the possibility of
      early diagnosis from MRI scans.

PMID- 18057084
TI  - Alpha7 nicotinic acetylcholine receptor gene and reduced risk of Alzheimer's
      disease.
AB  - BACKGROUND: Sporadic Alzheimer's disease (AD) is a common disabling disease of
      complex aetiology for which there are limited therapeutic options. We sought to
      investigate the role of the alpha7 nicotinic acetylcholine receptor gene (CHRNA7)
      in influencing risk of AD in a large population. CHRNA7 is a strong candidate
      gene for AD for several reasons: (1) its expression is altered differentially in
      the AD brain; (2) it interacts directly with beta amyloid peptide (Abeta(42));
      and (3) agonist activation induces several neuroprotective pathways. METHODS: In
      this study we used a genetic haplotype approach to assess the contribution of
      common variation at the CHRNA7 locus to risk of AD. Fourteen single nucleotide
      polymorphisms (SNPs) were genotyped in 764 AD patients and 314 controls. RESULTS:
      Three blocks of high linkage disequilibrium (LD) and low haplotype diversity were
      identified. The block 1 TCC haplotype was significantly associated with reduced
      odds of AD (p = 0.001) and was independent of apolipoprotein E (APOE) status.
      Individual SNPs were not associated with risk for AD. CONCLUSIONS: We conclude
      that genetic variation in CHRNA7 influences susceptibility to AD. These results
      provide support for the development of alpha7nAChR agonists or modulators as
      potential drug treatments for AD. Further work is necessary to replicate the
      findings in other populations.

PMID- 18057086
TI  - Factors associated with a second hip fracture: a systematic review.
AB  - OBJECTIVE: To provide a systematic review of factors associated with subsequent
      hip fracture among individuals who have fractured a hip. DATA SOURCES: We
      searched Ageline, CINAHL, EMBASE and MEDLINE, from database inceptions to the
      week of 5 June 2006. REVIEW METHODS: Studies were selected if they provided
      information regarding risk of subsequent hip fracture among individuals who had
      fractured a hip. Study quality was assessed using the Jadad criteria for
      randomized controlled trials (RCTs) and a simple scale based on the MOOSE
      criteria for cohort studies. RESULTS: Four RCTs and seven cohort studies were
      identified. Older age, cognitive impairment and lower bone mass appear to
      increase the risk of subsequent fracture, as did impaired depth perception,
      impaired mobility, previous falls, dizziness and poor or fair self-perceived
      health. Pharmacologic treatment for osteoporosis decreased the risk of subsequent
      fracture. Use of hip protectors by community-dwelling seniors did not appear to
      protect against a second fracture. CONCLUSION: A number of easily observed risk
      factors may help identify those individuals at higher risk for subsequent
      fracture.

PMID- 18057085
TI  - A family-specific use of the Measure of Processes of Care for Service Providers
      (MPOC-SP).
AB  - OBJECTIVE: To examine the validity and utility of the Dutch Measure of Processes
      of Care for Service Providers (MPOC-SP) as a family-specific measure. DESIGN: A
      validation study. SETTING: Five paediatric rehabilitation settings in the
      Netherlands. MAIN MEASURES: The MPOC-SP was utilized in a general (reflecting on
      services provided for all clients and clients' families) and family-specific way
      (filled out in reference to a particular child and his or her family). SUBJECTS:
      Professionals providing rehabilitation and educational services to children with
      cerebral palsy. METHODS: For construct validity, Pearson's product-moment
      correlation coefficients (r ) between the scales were calculated. The ability of
      service providers to discriminate between general and family-specific ratings was
      examined by exploration of absolute difference scores. RESULTS: One hundred and
      sixteen service professionals filled out 240 family-specific MPOC-SPs. In
      addition, a subgroup of 81 professionals filled out a general MPOC-SP. For each
      professional, family-specific and general scores were paired, resulting in 151
      general-family-specific MPOC-SP pairs. The construct validity analyses confirmed
      the scale structure: 21 items (77.8%) loaded highest in the original MPOC-SP
      factors, and all items correlated best and significantly with their own scale
      score (r 0.565 to 0.897; P<0.001). Intercorrelations between the scales ranged
      from r = 0.159 to r = 0.522. In total, 94.4% of the mean absolute difference
      scores between general and family-specific scale scores were larger than the
      expected difference. CONCLUSION: Service providers were able to discriminate
      between general and family-specific MPOC-SP item ratings. The family-specific
      MPOC-SP is a valid measure that can be used for individual evaluation of family
      centred services and can be the impetus for family-related quality improvement.

PMID- 18057087
TI  - Treadmill training for ataxic patients: a single-subject experimental design.
AB  - OBJECTIVE: To investigate changes in gait quality, balance and mobility
      associated with treadmill training for ataxic individuals. DESIGN: Single-subject
      ABA design. Baseline phases (A) lasted three weeks and intervention (B) lasted
      four weeks. SETTING: University rehabilitation clinic. SUBJECTS: A woman (25
      years) and a man (53 years) with chronic ataxia due to head trauma. INTERVENTION:
      Three 20-minute treadmill training sessions each week with progression in
      velocity and step length. MAIN MEASURES: Rivermead Visual Gait Assessment, Timed
      Up and Go, time to complete a balance task, walking speed, cadence, and stride
      length assessments three times a week during the 10 weeks. Data were analysed
      with the celeration line technique and two standard deviation band. RESULTS: Both
      individuals demonstrated gains in all parameters over initial baseline and
      subsequent phases, with performance increases ranging from 26% to 233% when first
      and last assessments were compared. Significantly superior effects of treadmill
      training over baseline conditions on cadence were detected (P<0.05). Gains in
      walking speed were not significantly better during intervention, but intervention
      withdrawal produced deceleration of performance gains. Gains in Timed Up and Go,
      step length and balance were not consistent and were possibly caused by a
      learning effect of the association between repeated testing and treadmill
      training. Rivermead Visual Gait Assessment gains reached significance only for
      subject 2 (P<0.05), probably because of increased variability of performance of
      subject 1. Results suggest that the association between repeated testing and
      treadmill training might have been responsible for the observed gains in the two
      ataxic patients.

PMID- 18057088
TI  - Prevention of pulmonary complications after upper abdominal surgery by
      preoperative intensive inspiratory muscle training: a randomized controlled pilot
      study.
AB  - OBJECTIVE: To investigate the feasibility and effects of preoperative inspiratory
      muscle training on the incidence of atelectasis in patients at high risk of
      postoperative pulmonary complications scheduled for elective abdominal aortic
      aneurysm surgery. DESIGN: Single-blind randomized controlled pilot study.
      SETTING: Gelderse Vallei Hospital Ede, the Netherlands. SUBJECTS: Twenty high
      risk patients undergoing elective abdominal aortic aneurysm surgery were randomly
      assigned to receive preoperative inspiratory muscle training or usual care. MAIN
      MEASURES: Effectiveness outcome variables were atelectasis, inspiratory muscle
      strength and vital capacity, and feasibility outcome variables were adverse
      effects and patient satisfaction with inspiratory muscle training. RESULTS:
      Despite randomization, patients in the intervention group were significantly
      older than the patients in the control group (70 +/- 6 years versus 59 +/- 6
      years, respectively; P = 0.001). Eight patients in the control group and three in
      the intervention group developed atelectasis (P = 0.07). The median duration of
      atelectasis was 0 days in the intervention group and 1.5 days in the control
      group (P = 0.07). No adverse effects of preoperative inspiratory muscle training
      were observed and patients considered that inspiratory muscle training was a good
      preparation for surgery. Mean postoperative inspiratory pressure was 10% higher
      in the intervention group. CONCLUSION: Preoperative inspiratory muscle training
      is well tolerated and appreciated and seems to reduce the incidence of
      atelectasis in patients scheduled for elective abdominal aortic aneurysm surgery.

PMID- 18057089
TI  - Postnatal programming of glucocorticoid metabolism in rats modulates high-fat
      diet-induced regulation of visceral adipose tissue glucocorticoid exposure and
      sensitivity and adiponectin and proinflammatory adipokines gene expression in
      adulthood.
AB  - OBJECTIVE: Alterations of the perinatal environment, which lead to increased
      prevalence of the metabolic syndrome in adulthood, program an upregulation of
      systemic and/or adipose tissue glucocorticoid metabolism (11 beta-hydroxysteroid
      dehydrogenase type 1 [11 beta-HSD-1]-induced corticosterone reactivation). We
      hypothesized that postnatal programming could modulate high-fat diet-induced
      adipose tissue dysregulation in adulthood. RESEARCH DESIGN AND METHODS: We
      compared the effects of chronic (since weaning) high- or low-fat diet in
      postnatally normofed (control) or overfed (programmed) rats. RESULTS: Postnatal
      programming accentuated high-fat diet-induced overweight, insulin resistance,
      glucose intolerance, and decrease in circulating and epididymal adipose tissue
      adiponectin. Neither manipulation altered liver function. Postnatal programming
      or high-fat diet increased systemic corticosterone production, which was not
      further modified when both manipulations were associated. Postnatal programming
      suppressed high-fat diet-induced decrease in mesenteric adipose tissue (MAT)
      glucocorticoid sensitivity and triggered high-fat diet-induced increase in MAT
      glucocorticoid exposure, subsequent to enhanced MAT 11 beta-HSD-1 gene
      expression. MAT tumor necrosis factor (TNF)-alpha, TNF-receptor 1, interleukin
      (IL)-6, resistin, and plasminogen activator inhibitor-1 mRNAs were not changed by
      high-fat feeding in control rats and showed a large increase in programmed
      animals, with this effect further enhanced by high-fat diet for TNF-alpha and IL
      6. CONCLUSIONS: Our data show for the first time that postnatal manipulation
      programs high-fat diet-induced upregulation of MAT glucocorticoid exposure,
      sensitivity, and inflammatory status and therefore reveal the pivotal role of the
      environment during the perinatal period on the development of diet-induced
      adipose tissue dysregulation in adulthood. They also urge the need for clinical
      trials with specific 11 beta-HSD-1 inhibitors.

PMID- 18057090
TI  - Thrombospondin-1 is an adipokine associated with obesity, adipose inflammation,
      and insulin resistance.
AB  - OBJECTIVE: We examined the relationship between the expression of thrombospondin
      (TSP)1, an antiangiogenic factor and regulator of transforming growth factor-beta
      activity, obesity, adipose inflammation, and insulin resistance. RESEARCH DESIGN
      AND METHODS: TSP1 gene expression was quantified in subcutaneous adipose tissue
      (SAT) of 86 nondiabetic subjects covering a wide range of BMI and insulin
      sensitivity, from visceral adipose (VAT) and SAT from 14 surgical patients and
      from 38 subjects with impaired glucose tolerance randomized to receive either
      pioglitazone or metformin for 10 weeks. An adipocyte culture system was also used
      to assess the effects of pioglitazone and coculture with macrophages on TSP1 gene
      expression. RESULTS: TSP1 mRNA was significantly associated with obesity (BMI)
      and insulin resistance (low insulin sensitivity index). Relatively strong
      positive associations were seen with markers of inflammation, including CD68,
      macrophage chemoattractant protein-1, and plasminogen activator inhibitor (PAI)-1
      mRNA (r >/= 0.46, P = 0.001 for each), that remained significant after
      controlling for BMI and S(i). However, TSP1 mRNA was preferentially expressed in
      adipocyte fraction, whereas inflammatory markers predominated in stromal vascular
      fraction. Coculture of adipocytes and macrophages augmented TSP1 gene expression
      and secretion from both cell types. Pioglitazone (not metformin) treatment
      resulted in a 54% decrease (P < 0.04) in adipose TSP gene expression, as did in
      vitro pioglitazone treatment of adipocytes. CONCLUSIONS: TSP1 is a true adipokine
      that is highly expressed in obese, insulin-resistant subjects; is highly
      correlated with adipose inflammation; and is decreased by pioglitazone. TSP1 is
      an important link between adipocytes and macrophage-driven adipose tissue
      inflammation and may mediate the elevation of PAI-1 that promotes a prothrombotic
      state.

PMID- 18057091
TI  - Predictors of incretin concentrations in subjects with normal, impaired, and
      diabetic glucose tolerance.
AB  - OBJECTIVE: Defects in glucagon-like peptide 1 (GLP-1) secretion have been
      reported in some patients with type 2 diabetes after meal ingestion. We addressed
      the following questions: 1) Is the quantitative impairment in GLP-1 levels
      different after mixed meal or isolated glucose ingestion? 2) Which endogenous
      factors are associated with the concentrations of GLP-1? In particular, do
      elevated fasting glucose or glucagon levels diminish GLP-1 responses? RESEARCH
      DESIGN AND METHODS: Seventeen patients with mild type 2 diabetes, 17 subjects
      with impaired glucose tolerance, and 14 matched control subjects participated in
      an oral glucose tolerance test (75 g) and a mixed meal challenge (820 kcal), both
      carried out over 240 min on separate occasions. Plasma levels of glucose,
      insulin, C-peptide, glucagon, triglycerides, free fatty acids (FFAs), gastric
      inhibitory polypeptide (GIP), and GLP-1 were determined. RESULTS: GIP and GLP-1
      levels increased significantly in both experiments (P < 0.0001). In patients with
      type 2 diabetes, the initial GIP response was exaggerated compared with control
      subjects after mixed meal (P < 0.001) but not after oral glucose ingestion (P =
      0.98). GLP-1 levels were similar in all three groups in both experiments. GIP
      responses were 186 +/- 17% higher after mixed meal ingestion than after the oral
      glucose load (P < 0.0001), whereas GLP-1 levels were similar in both experiments.
      There was a strong negative association between fasting glucagon and integrated
      FFA levels and subsequent GLP-1 concentrations. In contrast, fasting FFA and
      integrated glucagon levels after glucose or meal ingestion and female sex were
      positively related to GLP-1 concentrations. Incretin levels were unrelated to
      measures of glucose control or insulin secretion. CONCLUSIONS: Deteriorations in
      glucose homeostasis can develop in the absence of any impairment in GIP or GLP-1
      levels. This suggests that the defects in GLP-1 concentrations previously
      described in patients with long-standing type 2 diabetes are likely secondary to
      other hormonal and metabolic alterations, such as hyperglucagonemia. GIP and GLP
      1 concentrations appear to be regulated by different factors and are independent
      of each other.

PMID- 18057092
TI  - Insulin internalizes GLUT2 in the enterocytes of healthy but not insulin
      resistant mice.
AB  - OBJECTIVES: A physiological adaptation to a sugar-rich meal is achieved by
      increased sugar uptake to match dietary load, resulting from a rapid transient
      translocation of the fructose/glucose GLUT2 transporter to the brush border
      membrane (BBM) of enterocytes. The aim of this study was to define the
      contributors and physiological mechanisms controlling intestinal sugar
      absorption, focusing on the action of insulin and the contribution of GLUT2
      mediated transport. RESEARCH DESIGN AND METHODS: The studies were performed in
      the human enterocytic colon carcinoma TC7 subclone (Caco-2/TC7) cells and in vivo
      during hyperinsulinemic-euglycemic clamp experiments in conscious mice. Chronic
      high-fructose or high-fat diets were used to induce glucose intolerance and
      insulin resistance in mice. RESULTS AND CONCLUSIONS: In Caco-2/TC7 cells, insulin
      action diminished the transepithelial transfer of sugar and reduced BBM and
      basolateral membrane (BLM) GLUT2 levels, demonstrating that insulin can target
      sugar absorption by controlling the membrane localization of GLUT2 in
      enterocytes. Similarly, in hyperinsulinemic-euglycemic clamp experiments in
      sensitive mice, insulin abolished GLUT2 (i.e., the cytochalasin B-sensitive
      component of fructose absorption), decreased BBM GLUT2, and concomitantly
      increased intracellular GLUT2. Acute insulin treatment before sugar intake
      prevented the insertion of GLUT2 into the BBM. Insulin resistance in mice
      provoked a loss of GLUT2 trafficking, and GLUT2 levels remained permanently high
      in the BBM and low in the BLM. We propose that, in addition to its peripheral
      effects, insulin inhibits intestinal sugar absorption to prevent excessive blood
      glucose excursion after a sugar meal. This protective mechanism is lost in the
      insulin-resistant state induced by high-fat or high-fructose feeding.

PMID- 18057093
TI  - The repression of IRS2 gene by ATF3, a stress-inducible gene, contributes to
      pancreatic beta-cell apoptosis.
AB  - OBJECTIVE: beta-Cell failure is an essential component of all types of diabetes,
      and the insulin receptor substrate 2 (IRS2) branch of signaling plays a key role
      in beta-cell survival and function. We tested the hypothesis that activating
      transcription factor 3 (ATF3), a stress-inducible proapoptotic gene,
      downregulates the expression of IRS2 in beta-cells. RESEARCH DESIGN AND METHODS:
      We used both the gain- and loss-of-function approaches to test the effects of
      ATF3 on IRS2 gene expression. We also analyzed the binding of ATF3 to the IRS2
      promoter by chromatin immunoprecipitation assay and the transcription of the IRS2
      gene by polymerase II occupancy assay. Furthermore, we tested the ability of IRS2
      to alleviate the proapoptotic effects of ATF3 in cultured beta-cells and in
      transgenic mice using the rat insulin promoter to drive the transgenes. RESULTS:
      Expression of ATF3 is sufficient to reduce IRS2 gene expression; in contrast,
      knockdown or knockout of ATF3 reduces the ability of stress signals to
      downregulate IRS2 expression. ATF3 binds to the IRS2 promoter in vivo, and the
      binding of ATF3 correlates with decreased IRS2 gene transcription. Functionally,
      expression of IRS2 protects beta-cells from ATF3-induced apoptosis. CONCLUSIONS:
      IRS2 is a target gene of ATF3, and its repression by ATF3 contributes, at least
      partly, to the apoptosis induced by ATF3. Because ATF3 is a stress-inducible
      gene, our work provides a direct link to explain how environmental stress factors
      can modulate IRS2 gene transcription.

PMID- 18057095
TI  - Effect of non-invasive ventilation on respiratory muscle loading and endurance in
      patients with Duchenne muscular dystrophy.
AB  - BACKGROUND: Respiratory muscle weakness in patients with Duchenne muscular
      dystrophy (DMD) leads to respiratory failure for which non-invasive positive
      pressure ventilation (NIPPV) is an effective treatment. This is used initially at
      night (n-NIPPV) but, as the disease progresses, diurnal use (d-NIPPV) is often
      necessary. The connection between NIPPV and relief of respiratory muscle fatigue
      remains unclear. A study was undertaken to determine the extent to which n-NIPPV
      and d-NIPPV unload the respiratory muscles and improve respiratory endurance in
      patients with DMD. METHODS: Fifty patients with DMD were assessed at 20.00 and
      08.00 h. More severely affected patients with nocturnal hypoventilation received
      n-NIPPV; those with daytime dyspnoea also received d-NIPPV via a mouthpiece
      (14.00-16.00 h). Lung function, modified Borg dyspnoea score, spontaneous
      breathing pattern, tension-time index (TT(0.1) = occlusion pressure
      (P(0.1))/maximum inspiratory pressure (MIP) x duty cycle (Ti/Ttot)) and
      respiratory muscle endurance time (Tlim) against a threshold load of 35% MIP were
      measured. RESULTS: More severe respiratory muscle weakness was associated with a
      higher TT(0.1) and lower Tlim. In contrast to non-dyspnoeic patients, patients
      with dyspnoea (Borg score > 2.5/10) showed an increase in Tlim and decrease in
      TT(0.1) after n-NIPPV. At 16.00 h, immediately after d-NIPPV, patients with
      dyspnoea had lower TT(0.1) and Borg scores with unchanged Tlim. Compared with the
      control day without d-NIPPV, TT(0.1), Borg scores and Tlim were all improved at
      20.00 h. CONCLUSIONS: In patients with dyspnoea with DMD, the load on respiratory
      muscles increases and endurance capacity decreases with increasing breathlessness
      during the day, and this is reversed by n-NIPPV. An additional 2 h of d-NIPPV
      unloads respiratory muscles and reverses breathlessness more effectively than n
      NIPPV alone.

PMID- 18057094
TI  - A central role for neuronal AMP-activated protein kinase (AMPK) and mammalian
      target of rapamycin (mTOR) in high-protein diet-induced weight loss.
AB  - OBJECTIVE: A high-protein diet (HPD) is known to promote the reduction of body
      fat, but the mechanisms underlying this change are unclear. AMP-activated protein
      kinase (AMPK) and mammalian target of rapamycin (mTOR) function as majors
      regulators of cellular metabolism that respond to changes in energy status, and
      recent data demonstrated that they also play a critical role in systemic energy
      balance. Here, we sought to determine whether the response of the AMPK and mTOR
      pathways could contribute to the molecular effects of an HPD. RESEARCH DESIGN AND
      METHODS: Western blotting, confocal microscopy, chromatography, light microscopy,
      and RT-PCR assays were combined to explore the anorexigenic effects of an HPD.
      RESULTS: An HPD reduced food intake and induced weight loss in both normal rats
      and ob/ob mice. The intracerebroventricular administration of leucine reduced
      food intake, and the magnitude of weight loss and reduction of food intake in a
      leucine-supplemented diet are similar to that achieved by HPD in normal rats and
      in ob/ob mice, suggesting that leucine is a major component of the effects of an
      HPD. Leucine and HPD decrease AMPK and increase mTOR activity in the
      hypothalamus, leading to inhibition of neuropeptide Y and stimulation of pro
      opiomelanocortin expression. Consistent with a cross-regulation between AMPK and
      mTOR to control food intake, our data show that the activation of these enzymes
      occurs in the same specific neuronal subtypes. CONCLUSIONS: These findings
      provide support for the hypothesis that AMPK and mTOR interact in the
      hypothalamus to regulate feeding during HPD in a leucine-dependent manner.

PMID- 18057096
TI  - Telomerase activity in transthoracic fine needle biopsy aspirates as a marker of
      peripheral lung cancer.
AB  - BACKGROUND: A study was undertaken to evaluate the usefulness of telomerase
      activity assay in transthoracic fine needle biopsy (TFNB) aspirates collected
      from peripheral tumours of the lung in predicting the malignant aetiology of lung
      infiltrations. METHODS: 100 patients with a peripheral infiltration of the lung
      underwent TFNB of the focal lesion. The aspirates were subjected to standard
      cytological evaluation. Telomerase activity in the specimens was determined with
      the PCR-ELISA PLUS method. The sensitivity, specificity, accuracy and predictive
      value of TFNB were calculated for cytological examination of aspirates alone and
      cytological examination with additional telomerase activity assessment. RESULTS:
      Lung cancer was newly diagnosed in 84 subjects and benign peripheral lesions were
      found in 16. During the first TFNB, lung cancer was identified in 56 cases of
      cancer (66.7%) while increased telomerase activity was found in 61 cancer
      aspirates (72.6%). No subject with a benign infiltration had a false positive
      result from cytological examination, but in one case (6.25%) increased telomerase
      activity was observed. The diagnostic sensitivity, accuracy and negative
      predictive value of the combination of cytological examination and telomerase
      activity assay in TFNB specimens were significantly higher than for cytological
      examination alone (89.3% vs 66.7%, p = 0.0004; 90% vs 72%, p = 0.001; 62.5% vs
      36.4%, p = 0.039), but a combination of the two examinations was associated with
      a lower specificity of TFNB (96.9% vs 100%, p = 0.002). CONCLUSION: Detection of
      telomerase activity in aspirates taken during TFNB of a peripheral lung
      infiltration should be considered as an indication of the risk of malignancy in
      cases with false negative cytological results.

PMID- 18057097
TI  - Inter-relationships between inflammatory markers in patients with stable COPD
      with bronchitis: intra-patient and inter-patient variability.
AB  - BACKGROUND: Measurements of pulmonary biomarkers can be used to monitor airway
      inflammation in chronic obstructive pulmonary disease (COPD), but the variability
      of sampled biomarkers and their inter-relationships are poorly understood. A
      study was undertaken to examine the intra- and inter-patient variability in
      spontaneous sputum samples from patients in the stable state and to describe the
      relationship between biomarkers, cell counts and markers of disease. METHODS:
      Sputum interleukin-1beta, tumour necrosis factor alpha, interleukin 8,
      myeloperoxidase, leucotriene B4, growth-related oncogene alpha and differential
      cell counts were measured in patients with moderate to severe stable COPD (n =
      14) on 11 occasions over a 1-month period. RESULTS: There was significant
      variability in all inflammatory indices (median intra-patient coefficient of
      variation (CV) 35% (IQR 22-69), median inter-patient CV 102% (IQR 61-145)).
      Variability could be reduced by using a rolling mean of individual patient data
      points. Sample size calculations were undertaken to determine the number of
      patients required to detect a 50% reduction in neutrophil count. Using a
      crossover design of a putative effective treatment, the number needed using one
      data point per patient was 72, reducing to 23 when a mean of three data points
      was used. Significant correlations were demonstrated both between the
      inflammatory biomarkers themselves and between inflammatory biomarkers and
      markers of disease. Some relationships were not apparent when results from a
      single sample were used. The reliability of inter-relationships improved as more
      data points were used for each patient. CONCLUSIONS: Clear relationships exist
      between inflammatory biomarkers in patients with stable COPD. Sequential sampling
      reduced the variability of individual mediators and the potential number of
      patients needed to power proof of concept interventional studies.

PMID- 18057098
TI  - Glutathione S-transferase genotype increases risk of progression from bronchial
      hyperresponsiveness to asthma in adults.
AB  - BACKGROUND: Bronchial hyperresponsiveness (BHR) and variation in glutathione S
      transferase (GST) genes have been associated with asthma risk. The relationship
      of these two risk factors with adult onset asthma in the general population was
      investigated. METHODS: GSTP1 Ile105Val single nucleotide polymorphism and GSTM1
      and GSTT1 gene deletion polymorphisms were genotyped in the population
      representative SAPALDIA cohort. BHR was assessed at baseline by methacholine
      challenge and defined as a fall of > or =20% in forced expiratory volume in 1 s.
      Independent effects of GST polymorphisms and BHR on new onset of asthma after 11
      years of follow-up were estimated by multiple logistic regression analysis,
      adjusting for relevant baseline measures. Effect modification was assessed by
      including interaction terms in the model. RESULTS: Among 4426 asthma-free
      participants at baseline, 14% had BHR. At follow-up, 3.3% reported new onset of
      physician-diagnosed asthma. BHR (p<0.001) and GSTP1 Ile105Val genotype (p =
      0.005) were independently associated with incident asthma, but no association was
      seen for GSTT1 and GSTM1 gene deletion polymorphisms. Among subjects free of
      respiratory symptoms at baseline, the effect of BHR on the risk of physician
      diagnosed asthma at follow-up was restricted to GSTP1 105 Ile/Ile carriers (OR
      4.57, 95% CI 2.43 to 8.57 vs 1.40, 95% CI 0.58 to 3.39; p for interaction =
      0.023). CONCLUSIONS: If confirmed by independent studies, our results suggest
      that GSTP1 Ile105Val genotype strongly determines the progression of BHR to
      physician-diagnosed asthma in the general population.

PMID- 18057099
TI  - Wnt canonical pathway restricts graded Shh/Gli patterning activity through the
      regulation of Gli3 expression.
AB  - Dorsoventral patterning of the vertebrate nervous system is achieved by the
      combined activity of morphogenetic signals secreted from dorsal and ventral
      signalling centres. The Shh/Gli pathway plays a major role in patterning the
      ventral neural tube; however, the molecular mechanisms that limit target gene
      responses to specific progenitor domains remain unclear. Here, we show that
      Wnt1/Wnt3a, by signalling through the canonical beta-catenin/Tcf pathway, control
      expression of dorsal genes and suppression of the ventral programme, and that
      this role in DV patterning depends on Gli activity. Additionally, we show that
      Gli3 expression is controlled by Wnt activity. Identification and
      characterization of highly conserved non-coding DNA regions around the human Gli3
      gene revealed the presence of transcriptionally active Tcf-binding sequences.
      These indicated that dorsal Gli3 expression might be directly regulated by
      canonical Wnt activity. In turn, Gli3, by acting as a transcriptional repressor,
      restricted graded Shh/Gli ventral activity to properly pattern the spinal cord.

PMID- 18057100
TI  - Maternally derived FILIA-MATER complex localizes asymmetrically in cleavage-stage
      mouse embryos.
AB  - Initial cell lineages that presage the inner cell mass and extra-embryonic
      trophectoderm are established when eight blastomeres compact to form polarized
      morulae in preimplantation mouse development. FILIA has been identified as a
      binding partner to MATER (maternal antigen that embryos require; also known as
      NLRP5), which is encoded by a maternal effect gene. Products of each gene are
      detected in growing oocytes and, although transcripts are degraded before
      fertilization, the cognate proteins persist in early blastocysts. The two
      proteins co-localize to the cytocortex of ovulated eggs, where the stability of
      FILIA is dependent on the presence of MATER. After fertilization, FILIA-MATER
      complexes become asymmetrically restricted in the apical cytocortex of two-cell
      embryos due to their absence in regions of cell-cell contact. This asymmetry is
      reversible upon disaggregation of blastomeres of the two- and four-cell embryo.
      Each protein persists in cells of the preimplantation embryo, but the continuous
      cell-cell contact of ;inner' cells of the morulae seemingly precludes formation
      of the subcortical FILIA-MATER complex and results in cell populations that are
      marked by its presence (;outer') or absence (;inner'). Thus, the FILIA-MATER
      complex provides a molecular marker of embryonic cell lineages, but it remains to
      be determined if the molecular asymmetry established after the first cell
      division plays a role in cell fate determinations in the early mouse embryo. If
      so, the plasticity of the FILIA-MATER complex localization may reflect the
      regulative nature of preimplantation mouse development.

PMID- 18057101
TI  - The serine protease Corin is a novel modifier of the Agouti pathway.
AB  - The hair follicle is a model system for studying epithelial-mesenchymal
      interactions during organogenesis. Although analysis of the epithelial
      contribution to these interactions has progressed rapidly, the lack of tools to
      manipulate gene expression in the mesenchymal component, the dermal papilla, has
      hampered progress towards understanding the contribution of these cells. In this
      work, Corin was identified in a screen to detect genes specifically expressed in
      the dermal papilla. It is expressed in the dermal papilla of all pelage hair
      follicle types from the earliest stages of their formation, but is not expressed
      elsewhere in the skin. Mutation of the Corin gene reveals that it is not required
      for morphogenesis of the hair follicle. However, analysis of the ;dirty blonde'
      phenotype of these mice reveals that the transmembrane protease encoded by Corin
      plays a critical role in specifying coat color and acts downstream of agouti gene
      expression as a suppressor of the agouti pathway.

PMID- 18057102
TI  - Programmed cell death of primordial germ cells in Drosophila is regulated by p53
      and the Outsiders monocarboxylate transporter.
AB  - Primordial germ cell development uses programmed cell death to remove abnormal,
      misplaced or excess cells. Precise control of this process is essential to
      maintain the continuity and integrity of the germline, and to prevent germ cells
      from colonizing locations other than the gonads. Through careful analyses of
      primordial germ cell distribution in developing Drosophila melanogaster embryos,
      we show that normal germ cell development involves extensive programmed cell
      death during stages 10-12 of embryogenesis. This germ cell death is mediated by
      Drosophila p53 (p53). Mutations in p53 result in excess primordial germ cells
      that are ectopic to the gonads. Initial movements of the germ cells appear
      normal, and wild-type numbers of germ cells populate the gonads, indicating that
      p53 is required for germ cell death, but not migration. To our knowledge, this is
      the first report of a loss-of-function phenotype for Drosophila p53 in a non
      sensitized background. The p53 phenotype is remarkably similar to that of
      outsiders (out) mutants. Here, we show that the out gene encodes a putative
      monocarboxylate transporter. Mutations in p53 and out show nonallelic
      noncomplementation. Interestingly, overexpression of p53 in primordial germ cells
      of out mutant embryos partially suppresses the out germ cell death phenotype,
      suggesting that p53 functions in germ cells either downstream of out or in a
      closely linked pathway. These findings inform models in which signaling between
      p53 and cellular metabolism are integrated to regulate programmed cell death
      decisions.

PMID- 18057103
TI  - Convergence of a head-field selector Otx2 and Notch signaling: a mechanism for
      lens specification.
AB  - Xenopus is ideal for systematic decoding of cis-regulatory networks because its
      evolutionary position among vertebrates allows one to combine comparative
      genomics with efficient transgenic technology in one system. Here, we have
      identified and analyzed the major enhancer of FoxE3 (Lens1), a gene essential for
      lens formation that is activated in the presumptive lens ectoderm (PLE) when
      commitment to the lens fate occurs. Deletion and mutation analyses of the
      enhancer based on comparison of Xenopus and mammalian sequences and in vitro and
      in vivo binding assays identified two essential transcriptional regulators: Otx2,
      a homeodomain protein expressed broadly in head ectoderm including the PLE, and
      Su(H), a nuclear signal transducer of Notch signaling. A Notch ligand, Delta2, is
      expressed in the optic vesicle adjacent to the PLE, and inhibition of its
      activity led to loss, or severe reduction, of FoxE3 expression followed by
      failure of placode formation. Ectopic activation of Notch signaling induced FoxE3
      expression within head ectoderm expressing Otx2, and additional misexpression of
      Otx2 in trunk ectoderm extended the Notch-induced FoxE3 expression posteriorly.
      These data provide the first direct evidence of the involvement of Notch
      signaling in lens induction. The obligate integration of inputs of a field
      selector (Otx2) and localized signaling (Notch) within target cis-regulatory
      elements might be a general mechanism of organ-field specification in vertebrates
      (as it is in Drosophila). This concept is also consistent with classical
      embryological studies of many organ systems involving a ;multiple-step
      induction'.

PMID- 18057104
TI  - Crucial role of antisense transcription across the Xist promoter in Tsix-mediated
      Xist chromatin modification.
AB  - Expression of Xist, which triggers X inactivation, is negatively regulated in cis
      by an antisense gene, Tsix, transcribed along the entire Xist gene. We recently
      demonstrated that Tsix silences Xist through modification of the chromatin
      structure in the Xist promoter region. This finding prompted us to investigate
      the role of antisense transcription across the Xist promoter in Tsix-mediated
      silencing. Here, we prematurely terminated Tsix transcription before the Xist
      promoter and addressed its effect on Xist silencing in mouse embryos. We found
      that although 93% of the region encoding Tsix was transcribed, truncation of Tsix
      abolished the antisense regulation of Xist. This resulted in a failure to
      establish the repressive chromatin configuration at the Xist promoter on the
      mutated X, including DNA methylation and repressive histone modifications,
      especially in extraembryonic tissues. These results suggest a crucial role for
      antisense transcription across the Xist promoter in Xist silencing.

PMID- 18057105
TI  - A shout out to immature synapses. Focus on "different roles for AMPA and NMDA
      receptors in transmission at the immature retinogeniculate synapse".

PMID- 18057106
TI  - Recruiting extrasynaptic NMDA receptors augments synaptic signaling.
AB  - N-Methyl-d-aspartate receptor (NMDAR) activation may promote cell survival or
      initiate cell death, with the outcome dependent on whether synaptic or
      extrasynaptic receptors are activated. Similarly, this differential activation
      has been proposed to govern the direction of plasticity. However, the
      physiological parameters necessary to activate extrasynaptic NMDARs in brain
      slices remain unknown. Using the irreversible use-dependent NMDAR antagonist MK
      801 to isolate extrasynaptic NMDARs, we have tested the ability of short
      stimulation trains from 5 to 400 Hz to activate these receptors on CA1
      hippocampal slice pyramidal neurons. Frequencies as low as 25 Hz engage
      extrasynaptic NMDARs, with maximal activation at frequencies between 100 and 200
      Hz. Since similar bursts of synaptic input occur during exploratory behavior in
      rats, our results demonstrate that "extrasynaptic" NMDARs regularly participate
      in synaptic transmission. Further, 175-Hz-stimulation trains activate all
      available synaptic and extrasynaptic dendritic NMDARs, suggesting these NMDARs
      act as synaptic receptors as needed, transiently increasing synaptic strength.
      Thus extrasynaptic NMDARs play a vital role in synaptic physiology, calling into
      question their status as "extrasynaptic."

PMID- 18057107
TI  - Dynamic I-V curves are reliable predictors of naturalistic pyramidal-neuron
      voltage traces.
AB  - Neuronal response properties are typically probed by intracellular measurements
      of current-voltage (I-V) relationships during application of current or voltage
      steps. Here we demonstrate the measurement of a novel I-V curve measured while
      the neuron exhibits a fluctuating voltage and emits spikes. This dynamic I-V
      curve requires only a few tens of seconds of experimental time and so lends
      itself readily to the rapid classification of cell type, quantification of
      heterogeneities in cell populations, and generation of reduced analytical models.
      We apply this technique to layer-5 pyramidal cells and show that their dynamic I
      V curve comprises linear and exponential components, providing experimental
      evidence for a recently proposed theoretical model. The approach also allows us
      to determine the change of neuronal response properties after a spike,
      millisecond by millisecond, so that postspike refractoriness of pyramidal cells
      can be quantified. Observations of I-V curves during and in absence of
      refractoriness are cast into a model that is used to predict both the
      subthreshold response and spiking activity of the neuron to novel stimuli. The
      predictions of the resulting model are in excellent agreement with experimental
      data and close to the intrinsic neuronal reproducibility to repeated stimuli.

PMID- 18057108
TI  - The influence of briefly presented randomized target motion on the extraretinal
      component of ocular pursuit.
AB  - We assessed the ability to extract velocity information from brief exposure of a
      moving target and sought evidence that this information could be used to modulate
      the extraretinal component of ocular pursuit. A step-ramp target motion was
      initially visible for a brief randomized period of 50, 100, 150, or 200 ms, but
      then extinguished for a randomized period of 400 or 600 ms before reappearing and
      continuing along its trajectory. Target speed (5-20 degrees /s), direction
      (left/right), and intertrial interval (2.7-3.7 s) were also randomized. Smooth
      eye movements were initiated after about 130 ms and comprised an initial visually
      dependent component, which reached a peak velocity that increased with target
      velocity and initial exposure duration, followed by a sustained secondary
      component that actually increased throughout extinction for 50- and 100-ms
      initial exposures. End-extinction eye velocity, reflecting extraretinal drive,
      increased with initial exposure from 50 to 100 ms but remained similar for longer
      exposures; it was significantly scaled to target velocity for 150- and 200-ms
      exposures. The results suggest that extraretinal drive is based on a sample of
      target velocity, mostly acquired during the first 150 ms, that is stored and
      forms a goal for generating appropriately scaled eye movements during absence of
      visual input. End-extinction eye velocity was significantly higher when target
      reappearance was expected than when it was not, confirming the importance of
      expectation in generating sustained smooth movement. However, end-extinction eye
      displacement remained similar irrespective of expectation, suggesting that the
      ability to use sampled velocity information to predict future target displacement
      operates independently of the control of smooth eye movement.

PMID- 18057109
TI  - Role of TTX-sensitive and TTX-resistant sodium channels in Adelta- and C-fiber
      conduction and synaptic transmission.
AB  - Thin afferent axons conduct nociceptive signals from the periphery to the spinal
      cord. Their somata express two classes of Na+ channels, TTX-sensitive (TTX-S) and
      TTX-resistant (TTX-R), but their relative contribution to axonal conduction and
      synaptic transmission is not well understood. We studied this contribution by
      comparing effects of nanomolar TTX concentrations on currents associated with
      compound action potentials in the peripheral and central branches of Adelta- and
      C-fiber axons as well as on the Adelta- and C-fiber-mediated excitatory
      postsynaptic currents (EPSCs) in spinal dorsal horn neurons of rat. At room
      temperature, TTX completely blocked Adelta-fibers (IC50, 5-7 nM) in dorsal roots
      (central branch) and spinal, sciatic, and sural nerves (peripheral branch). The C
      fiber responses were blocked by 85-89% in the peripheral branch and by 65-66% in
      dorsal roots (IC50, 14-33 nM) with simultaneous threefold reduction in their
      conduction velocity. At physiological temperature, the degree of TTX block in
      dorsal roots increased to 93%. The Adelta- and C-fiber-mediated EPSCs in dorsal
      horn neurons were also sensitive to TTX. At room temperature, 30 nM blocked
      completely Adelta-input and 84% of the C-fiber input, which was completely
      suppressed at 300 nM TTX. We conclude that in mammals, the TTX-S Na+ channels
      dominate conduction in all thin primary afferents. It is the only type of
      functional Na+ channel in Adelta-fibers. In C-fibers, the TTX-S Na+ channels
      determine the physiological conduction velocity and control synaptic
      transmission. TTX-R Na+ channels could not provide propagation of full-amplitude
      spikes able to trigger synaptic release in the spinal cord.

PMID- 18057110
TI  - Vestibular nuclei and cerebellum put visual gravitational motion in context.
AB  - Animal survival in the forest, and human success on the sports field, often
      depend on the ability to seize a target on the fly. All bodies fall at the same
      rate in the gravitational field, but the corresponding retinal motion varies with
      apparent viewing distance. How then does the brain predict time-to-collision
      under gravity? A perspective context from natural or pictorial settings might
      afford accurate predictions of gravity's effects via the recovery of an
      environmental reference from the scene structure. We report that embedding motion
      in a pictorial scene facilitates interception of gravitational acceleration over
      unnatural acceleration, whereas a blank scene eliminates such bias. Functional
      magnetic resonance imaging (fMRI) revealed blood-oxygen-level-dependent
      correlates of these visual context effects on gravitational motion processing in
      the vestibular nuclei and posterior cerebellar vermis. Our results suggest an
      early stage of integration of high-level visual analysis with gravity-related
      motion information, which may represent the substrate for perceptual constancy of
      ubiquitous gravitational motion.

PMID- 18057111
TI  - Neurokinin-1 receptors modulate the excitability of expiratory neurons in the
      ventral respiratory group.
AB  - We studied the role of neurokinin-1 receptors (NK1-R) on the excitability of
      expiratory (E) neurons (tonic discharge, E(TONIC); augmenting, E(AUG);
      decrementing, E(DEC)) throughout the ventral respiratory group, including
      Botzinger Complex (BotC) using extracellular single-unit recording combined with
      pressurized picoejection in decerebrate, arterially perfused juvenile rats.
      Responses evoked by picoejection of the NK1-R agonist, [Sar9-Met(O2)11]-substance
      P (SSP) were determined before and after the selective NK1-R antagonist,
      CP99,994. SSP excited 20 of 35 expiratory neurons by increasing the number of
      action potentials per burst (+33.7 +/- 6.5% of control), burst duration (+20.6 +/
      7.9% of control), and peak firing frequency (+16.2 +/- 4.8% of control; means +/
      SE). Pretreatment with CP99,994 completely blocked SSP-evoked excitation in a
      subset of neurons tested, supporting the notion that SSP excitation was mediated
      through NK1-R activation. Because we had previously shown that E(AUG) neurons
      were crucial to locomotor-respiratory coupling (LRC), we reasoned that blockade
      of NK1-R would alter LRC by preventing somatic-evoked excitation of E(AUG)
      neurons. Blockade of NK1-Rs by CP99,994 in the BotC severely disrupted LRC and
      prevented somatic-evoked excitation of E(AUG) neurons. These findings demonstrate
      that LRC is dependent on endogenous SP release acting via NK1-Rs on E(AUG)
      neurons of the BotC. Taken together with our earlier finding that inspiratory off
      switching by the Hering-Breuer Reflex requires endogenous activation of NK1-Rs
      through activation of NK1-Rs on E(DEC) neurons, we suggest that endogenous
      release of substance P in the BotC provides a reflex pathway-dependent mechanism
      to selectively modulate respiratory rhythm.

PMID- 18057113
TI  - Preconditioning repetitive transcranial magnetic stimulation of premotor cortex
      can reduce but not enhance short-term facilitation of primary motor cortex.
AB  - Short trains of suprathreshold 5-Hz repetitive transcranial magnetic stimulation
      (rTMS) over primary motor cortex (M1) evoke motor potentials (MEPs) in hand
      muscles that progressively increase in amplitude via a mechanism that is thought
      to be similar to short-term potentiation described in animal preparations. Long
      trains of subthreshold rTMS over dorsal premotor cortex (PMd) are known to affect
      the amplitude of single-pulse MEPs evoked from M1. We tested whether PMd-rTMS
      affects short-term facilitation in M1. We also explored the effect of PMd-rTMS on
      M1 responses evoked by single-pulse TMS of different polarities. We tested in 15
      healthy subjects short-term facilitation in left M1 (10 suprathreshold TMS pulses
      at 5 Hz) after applying rTMS to left PMd (1,500 subthreshold pulses at 1 and 5
      Hz). In a sample of subjects we delivered single-pulse TMS with different
      polarities and paired-pulse TMS at short intervals (SICI) after PMd-rTMS. Short
      term facilitation in M1 was reduced after applying 1 Hz to PMd, but was
      unaffected after 5-Hz PMd-rTMS. PMd-rTMS with 1 Hz reduced the amplitude of MEPs
      evoked by monophasic posteroanterior (PA) or biphasic anteroposterior (AP)-PA but
      had little effect on MEPs by monophasic AP or biphasic PA-AP single-pulse TMS.
      PMd-rTMS left SICI unchanged. PMd-rTMS (1 Hz) reduces short-term facilitation in
      M1 induced by short 5-Hz trains. This effect is likely to be caused by reduced
      facilitation of I-wave inputs to corticospinal neurons.

PMID- 18057112
TI  - Polarized skylight navigation in insects: model and electrophysiology of e-vector
      coding by neurons in the central complex.
AB  - Many insects exploit skylight polarization for visual compass orientation or
      course control. As found in crickets, the peripheral visual system (optic lobe)
      contains three types of polarization-sensitive neurons (POL neurons), which are
      tuned to different ( approximately 60 degrees diverging) e-vector orientations.
      Thus each e-vector orientation elicits a specific combination of activities among
      the POL neurons coding any e-vector orientation by just three neural signals. In
      this study, we hypothesize that in the presumed orientation center of the brain
      (central complex) e-vector orientation is population-coded by a set of "compass
      neurons." Using computer modeling, we present a neural network model transforming
      the signal triplet provided by the POL neurons to compass neuron activities
      coding e-vector orientation by a population code. Using intracellular
      electrophysiology and cell marking, we present evidence that neurons with the
      response profile of the presumed compass neurons do indeed exist in the insect
      brain: each of these compass neuron-like (CNL) cells is activated by a specific e
      vector orientation only and otherwise remains silent. Morphologically, CNL cells
      are tangential neurons extending from the lateral accessory lobe to the lower
      division of the central body. Surpassing the modeled compass neurons in
      performance, CNL cells are insensitive to the degree of polarization of the
      stimulus between 99% and at least down to 18% polarization and thus largely
      disregard variations of skylight polarization due to changing solar elevations or
      atmospheric conditions. This suggests that the polarization vision system
      includes a gain control circuit keeping the output activity at a constant level.

PMID- 18057114
TI  - Coherent motor unit rhythms in the 6-10 Hz range during time-varying voluntary
      muscle contractions: neural mechanism and relation to rhythmical motor control.
AB  - In quasi-sinusoidal (0.5-3.0 Hz) voluntary muscle contractions, we studied the 6-
      to 10-Hz motor unit (MU) firing synchrony and muscle force oscillation with
      emphasis on their neural substrate and relation to rhythmical motor control. Our
      analyses were performed on data from 121 contractions of a finger muscle in 24
      human subjects. They demonstrate that coherent 6- to 10-Hz components of MU
      discharges coexist with carrier components and coherent modulation components
      underlying the voluntary force variations. The 6- to 10-Hz synchrony has the
      frequency of the tremor synchrony in steady contractions and is also widespread
      and in-phase. Its strength ranges from very small to very large (MU/MU coherence
      >0.50) among contractions; moreover, it is not related to the contraction
      parameters, in accord with the notion of a distinct 6- to 10-Hz synaptic input to
      the MUs. Unlike the coherent MU modulations and the voluntary force variations,
      the in-phase 6- to 10-Hz MU components are suppressed or even eliminated during
      ischemia, while the respective force component is drastically reduced. These
      findings agree with the widely assumed supraspinal origin of the MU modulations,
      but they also strongly suggest a key role for muscle spindle feedback in the
      generation of the 6- to 10-Hz synaptic input. They therefore provide important
      information for the study of generators of the 6- to 10-Hz rhythm which subserves
      the postulated rhythmical control and is manifested as force and movement
      components. Moreover, they argue for a participation of oscillating spinal
      stretch reflex loops in the rhythm generation, possibly in interaction with
      supraspinal oscillators.

PMID- 18057115
TI  - Subthreshold K+ channel dynamics interact with stimulus spectrum to influence
      temporal coding in an auditory brain stem model.
AB  - Neurons in the auditory brain stem encode signals with exceptional temporal
      precision. A low-threshold potassium current, IKLT, present in many auditory
      brain stem structures and thought to enhance temporal encoding, facilitates spike
      selection of rapid input current transients through an associated dynamic gate.
      Whether the dynamic nature of IKLT interacts with the timescales in spectrally
      rich input to influence spike encoding remains unclear. We examine the general
      influence of IKLT on spike encoding of stochastic stimuli using a pattern
      classification analysis between spike responses from a ventral cochlear nucleus
      (VCN) model containing IKLT, and the same model with the IKLT dynamics removed.
      The influence of IKLT on spike encoding depended on the spectral content of the
      current stimulus such that maximal IKLT influence occurred for stimuli with power
      concentrated at frequencies low enough (<500 Hz) to allow IKLT activation.
      Further, broadband stimuli significantly decreased the influence of IKLT on spike
      encoding, suggesting that broadband stimuli are not well suited for investigating
      the influence of some dynamic membrane nonlinearities. Finally, pattern
      classification on spike responses was performed for physiologically realistic
      conductance stimuli created from various sounds filtered through an auditory
      nerve (AN) model. Regardless of the sound, the synaptic input arriving at VCN had
      similar low-pass power spectra, which led to a large influence of IKLT on spike
      encoding, suggesting that the subthreshold dynamics of IKLT plays a significant
      role in shaping the response of real auditory brain stem neurons.

PMID- 18057116
TI  - Enzymatic C-demethylation of 1-[2-(5-tert-butyl-[1,3,4] oxadiazole-2-carbonyl)-4
      fluoro-pyrrolidin-1-yl]-2-(2-hydroxy-1,1-dimethyl-ethylamino)-ethanone (LC15
      0133) in rat liver microsomes.
AB  - The in vitro metabolism of 1-[2-(5-tert-butyl-[1,3,4] oxadiazole-2-carbonyl)-4
      fluoro-pyrrolidin-1-yl]-2-(2-hydroxy-1,1-dimethyl-ethylamino)-ethanone (LC15
      0133), a novel dipeptidyl peptidase-4 inhibitor, was investigated using a hepatic
      microsomal system. The structures of the metabolites were characterized using
      mass spectral analysis and by comparison with synthetic references. The in vitro
      incubation of LC15-0133 with rat liver microsomes resulted in the formation of
      six metabolites, with the major metabolic reactions being hydroxylation and
      carbonyl reduction. Of the metabolites, a C-demethylated metabolite (M4) was
      identified, but was only detected in rat liver microsomes; experimental evidence
      revealed that the C-demethylated metabolite was generated by nonenzymatic
      decarboxylation of the carboxyl metabolite (M1). Nonenzymatic decarboxylation is
      postulated to occur due to the resonance stabilization by the oxadiazole ring
      attached to the tert-butyl moiety.

PMID- 18057117
TI  - In vitro-to-in vivo prediction of P-glycoprotein-based drug interactions at the
      human and rodent blood-brain barrier.
AB  - In vitro inhibition of P-glycoprotein (P-gp) expressed in cells is routinely used
      to predict the potential of in vivo P-gp drug interactions at the human blood
      brain barrier (BBB). The accuracy of such predictions has not been confirmed
      because methods to quantify in vivo P-gp drug interactions at the human BBB have
      not been available. With the development of a noninvasive positron emission
      topography (PET) imaging method by our laboratory to determine P-gp-based drug
      interactions at the human BBB, an in vitro-in vivo comparison is now possible.
      Therefore, we developed a high throughput cell-based assay to determine the
      potential of putative P-gp inhibitors [including cyclosporine A (CsA)] to inhibit
      (EC(50)) the efflux of verapamil-bodipy, a model P-gp substrate. LLCPK1-MDR1
      cells, expressing recombinant human P-gp, or control cells lacking P-gp (LLCPK1)
      were used in our assay. Using this assay, quinine, quinidine, CsA, and amprenavir
      were predicted to be the most potent P-gp inhibitors in vivo at their respective
      therapeutic maximal unbound plasma concentrations. The in vitro EC(50) of CsA
      (0.6 microM) for P-gp inhibition was virtually the same as our previously
      determined in vivo unbound EC(50) at the rat BBB (0.5 microM). Moreover, at 2.8
      microM CsA (total blood concentration), our in vitro data predicted an increase
      of 129% in [(11)C]verapamil distribution into the human brain, a value similar to
      that observed by us (79%) using PET. These data suggest that our high throughput
      cell assay has the potential to accurately predict P-gp drug interactions at the
      human BBB.

PMID- 18057118
TI  - Bistable MAP kinase activity: a plausible mechanism contributing to maintenance
      of late long-term potentiation.
AB  - Bistability of MAP kinase (MAPK) activity has been suggested to contribute to
      several cellular processes, including differentiation and long-term synaptic
      potentiation. A recent model (Markevich NI, Hoek JB, Kholodenko BN. J Cell Biol
      164: 353-359, 2004) predicts bistability due to interactions of the kinases and
      phosphatases in the MAPK pathway, without feedback from MAPK to earlier
      reactions. Using this model and enzyme concentrations appropriate for neurons, we
      simulated bistable MAPK activity, but bistability was present only within a
      relatively narrow range of activity of Raf, the first pathway kinase. Stochastic
      fluctuations in molecule numbers eliminated bistability for small molecule
      numbers, such as are expected in the volume of a dendritic spine. However,
      positive-feedback loops have been posited from MAPK up to Raf activation. One
      proposed loop in which MAPK directly activates Raf was incorporated into the
      model. We found that such feedback greatly enhanced the robustness of both stable
      states of MAPK activity to stochastic fluctuations and to parameter variations.
      Bistability was robust for molecule numbers plausible for a dendritic spine
      volume. The upper state of MAPK activity was resistant to inhibition of MEK
      activation for >1 h, which suggests that inhibitor experiments have not sufficed
      to rule out a role for persistent MAPK activity in the maintenance of long-term
      potentiation (LTP). These simulations suggest that persistent MAPK activity and
      consequent upregulation of translation may contribute to LTP maintenance and to
      long-term memory. Experiments using a fluorescent MAPK substrate may further test
      this hypothesis.

PMID- 18057119
TI  - Influence of microvascular endothelial cells on transcriptional regulation of
      proximal tubular epithelial cells.
AB  - In the renal cortex the peritubular capillary network and the proximal tubular
      epithelium cooperate in solute and water reabsorption, secretion, and
      inflammation. However, the mechanisms by which these two cell types coordinate
      such diverse functions remain to be characterized. Here we investigated the
      influence of microvascular endothelial cells on proximal tubule cells, using a
      filter-based, noncontact, close-proximity coculture of the human microvascular
      endothelial cell line HMEC-1 and the human proximal tubular epithelial cell line
      HK-2. With the use of DNA microarrays the transcriptomes of HK-2 cells cultured
      in mono- and coculture were compared. HK-2 cells in coculture exhibited a
      differential expression of 99 genes involved in pathways such as extracellular
      matrix (e.g., lysyl oxidase), cell-cell communication (e.g., IL-6 and IL-1 beta),
      and transport (e.g., GLUT3 and lipocalin 2). HK-2 cells also exhibited an
      enhanced paracellular gating function in coculture, which was dependent on HMEC-1
      derived extracellular matrix. We identified a number of HMEC-1-enriched genes
      that are potential regulators of epithelial cell function such as extracellular
      matrix proteins (e.g., collagen I, III, IV, and V, laminin-alpha IV) and
      cytokines/growth factors (e.g., hepatocyte growth factor, endothelin-1, VEGF-C).
      This study demonstrates a complex network of communication between microvascular
      endothelial cells and proximal tubular epithelial cells that ultimately affects
      proximal tubular cell function. This coculture model and the data described will
      be important in the further elucidation of microvascular endothelial and proximal
      tubular epithelial cross talk mechanisms.

PMID- 18057120
TI  - Opposing effects of coupled and uncoupled NOS activity on the Na+-K+ pump in
      cardiac myocytes.
AB  - Pharmacological delivery of nitric oxide (NO) stimulates the cardiac Na(+)-K(+)
      pump. However, effects of NO synthesized by NO synthase (NOS) often differ from
      the effects of NO delivered pharmacologically. In addition, NOS can become
      "uncoupled" and preferentially synthesize O(2)(.-), which often has opposing
      effects to NO. We tested the hypothesis that NOS-synthesized NO stimulates Na(+)
      K(+) pump activity, and uncoupling of NOS inhibits it. To image NO, we loaded
      isolated rabbit cardiac myocytes with 4,5-diaminofluorescein-2 diacetate (DAF-2
      DA) and measured fluorescence with confocal microscopy. L-arginine (L-arg; 500
      micromol/l) increased DAF-2 DA fluorescence by 51% compared with control (n = 8;
      P < 0.05). We used the whole cell patch-clamp technique to measure electrogenic
      Na(+)-K(+) pump current (I(p)). Mean I(p) of 0.35 +/- 0.03 pA/pF (n = 44) was
      increased to 0.48 +/- 0.03 pA/pF (n = 7, P < 0.05) by 10 micromol/l L-Arg in
      pipette solutions. This increase was abolished by NOS inhibition with radicicol
      or by NO-activated guanylyl cyclase inhibition with 1H-[1,2,4]oxadiazole[4,3
      a]quinoxalin-1-one. We next examined the effect of uncoupling NOS using paraquat.
      Paraquat (1 mmol/l) induced a 51% increase in the fluorescence intensity of
      O(2)(.-)-sensitive dye dihydroethidium compared with control (n = 9; P < 0.05).
      To examine the functional effects of uncoupling, we measured I(p) with 100
      micromol/l paraquat included in patch pipette solutions. This decreased I(p) to
      0.28 +/- 0.03 pA/pF (n = 12; P < 0.001). The paraquat-induced pump inhibition was
      abolished by superoxide dismutase (in pipette solutions). We conclude that NOS
      mediated NO synthesis stimulates the Na(+)-K(+) pump, whereas uncoupling of NOS
      causes O(2)(.-)-mediated pump inhibition.

PMID- 18057121
TI  - Identification and characterization of a novel family of membrane magnesium
      transporters, MMgT1 and MMgT2.
AB  - Magnesium is an essential metal, but few selective transporters have been
      identified at the molecular level. Microarray analysis was used to identify two
      similar transcripts that are upregulated with low extracellular Mg(2+). The
      corresponding cDNAs encode proteins of 131 and 123 amino acids with two predicted
      transmembrane domains. The two separate gene products comprise the family that we
      have termed "membrane Mg(2+) transporters" (MMgTs), because the proteins reside
      in the membrane and mediate Mg(2+) transport. When expressed in Xenopus laevis
      oocytes, MMgT1 and MMgT2 mediate Mg(2+) transport as determined with two
      electrode voltage-clamp analysis and fluorescence measurements. Transport is
      saturable Mg(2+) uptake with Michaelis constants of 1.47 +/- 0.17 and 0.58 +/-
      0.07 mM, respectively. Real-time RT-PCR demonstrated that MMgT mRNAs are present
      in a wide variety of cells. Subcellular localization with immunohistochemistry
      determined that the MMgT1-hemagglutinin (HA) and MMgT2-V5 fusion proteins reside
      in the Golgi complex and post-Golgi vesicles, including the early endosomes in
      COS-7 cells transfected with the respective tagged constructs. Interestingly,
      MMgT1-HA and MMgT2-V5 were found in separate populations of post-Golgi vesicles.
      MMgT1 and MMgT2 mRNA increased by about threefold, respectively, in kidney
      epithelial cells cultured in low-magnesium media relative to normal media and in
      the kidney cortex of mice maintained on low-magnesium diets compared with those
      animals consuming normal diets. With the increase in transcripts, there was an
      apparent increase in MMgT1 and MMgT2 protein in the Golgi and post-Golgi
      vesicles. These experiments suggest that MMgT proteins may provide regulated
      pathways for Mg(2+) transport in the Golgi and post-Golgi organelles of
      epithelium-derived cells.

PMID- 18057122
TI  - Novel insights into intestinal and renal folate transport. Focus on "Apical
      membrane targeting and trafficking of the human proton-coupled folate transporter
      in polarized epithelia".

PMID- 18057123
TI  - Prevalence, types, and RNA concentrations of human parechoviruses, including a
      sixth parechovirus type, in stool samples from patients with acute enteritis.
AB  - Parechovirus epidemiology and disease association are not fully understood. Real
      time reverse transcriptase PCR (RT-PCR) for all human parechoviruses (HPeV) was
      applied on stool samples from two groups of patients. Both groups contained
      patients with acute enteritis of all age groups, seen during one full year.
      Patients with norovirus, adenovirus, enterovirus, astrovirus, or rotavirus
      infections were excluded. In 118 patients from outbreak and hospital settings, no
      HPeV was detected. In a prospective study group of 499 nonhospitalized patients,
      the detection rate was 1.6%. One virus-positive patient was detected from 39
      control patients. Positive samples occurred only in summer and autumn. Only one
      patient had accompanying respiratory symptoms. An association with travel or
      animal contact was not found. All positive patients except one were <2 years of
      age, with a neutral gender ratio. In children <2 years of age, the detection rate
      was 11.6% (7 of 60 children). The range of viral loads was 3,170 to 503,377,290
      copies per gram or milliliter of stool. One of the highest viral loads occurred
      in a control child without symptoms at the time of testing. Phylogenetic analysis
      showed mainly contemporary HPeV1 strains in our patients but also showed a
      separate new lineage of HPeV1 in evolutionary transition from the historical
      prototype strain. Moreover, a novel sixth HPeV type was identified. Full genome
      analysis of the two viruses revealed recombination between HPeV1 and -3 in one
      and HPeV6 and -1 in another. HPeV seems relevant in children <2 years and
      specific RT-PCR for HPeV should be included in enteritis screening.

PMID- 18057124
TI  - Beta-lactam failure in treatment of two group G Streptococcus dysgalactiae subsp.
      equisimilis Pharyngitis patients.
AB  - We present two cases of exudative pharyngitis due to Streptococcus dysgalactiae
      subsp. equisimilis, Lancefield group G. While the participation of this organism
      as an agent of pharyngitis is well documented, we focus on failure of beta-lactam
      therapy, a phenomenon that is well described for pharyngitis due to Streptococcus
      pyogenes. Therefore, these case reports add to our knowledge of pharyngitis
      caused by non-S. pyogenes streptococci.

PMID- 18057125
TI  - Multilocus sequence typing reveals that the population structure of Candida
      dubliniensis is significantly less divergent than that of Candida albicans.
AB  - The pathogenic yeast Candida dubliniensis is phylogenetically very closely
      related to Candida albicans, and both species share many phenotypic and genetic
      characteristics. DNA fingerprinting using the species-specific probe Cd25 and
      sequence analysis of the internal transcribed spacer (ITS) region of the
      ribosomal gene cluster previously showed that C. dubliniensis is comprised of
      three major clades comprising four distinct ITS genotypes. Multilocus sequence
      typing (MLST) has been shown to be very useful for investigating the epidemiology
      and population biology of C. albicans and has identified many distinct major and
      minor clades. In the present study, we used MLST to investigate the population
      structure of C. dubliniensis for the first time. Combinations of 10 loci
      previously tested for MLST analysis of C. albicans were assessed for their
      discriminatory ability with 50 epidemiologically unrelated C. dubliniensis
      isolates from diverse geographic locations, including representative isolates
      from the previously identified three Cd25-defined major clades and the four ITS
      genotypes. Dendrograms created by using the unweighted pair group method with
      arithmetic averages that were generated using the data from all 10 loci revealed
      a population structure which supports that previously suggested by DNA
      fingerprinting and ITS genotyping. The MLST data revealed significantly less
      divergence within the C. dubliniensis population examined than within the C.
      albicans population. These findings show that MLST can be used as an informative
      alternative strategy for investigating the population structure of C.
      dubliniensis. On the basis of the highest number of genotypes per variable base,
      we recommend the following eight loci for MLST analysis of C. dubliniensis:
      CdAAT1b, CdACC1, CdADP1, CdMPIb, CdRPN2, CdSYA1, exCdVPS13, and exCdZWF1b, where
      "Cd" indicates C. dubliniensis and "ex" indicates extended sequence.

PMID- 18057126
TI  - Evaluation of the one-step multiplex real-time reverse transcription-PCR ProFlu-1
      assay for detection of influenza A and influenza B viruses and respiratory
      syncytial viruses in children.
AB  - We evaluated the one-step multiplex real-time reverse transcription-PCR ProFlu-1
      assay for the detection of influenza A and influenza B viruses and respiratory
      syncytial viruses from 353 pediatric nasopharyngeal aspirates. As assessed by
      comparison with the results of immunofluorescence testing and cell culture, the
      specificity and the sensitivity of the ProFlu-1 assay ranged from 97% to 100%. In
      addition, the ProFlu-1 assay amplified 9% of samples not detected by conventional
      methods.

PMID- 18057127
TI  - Development of a microtiter plate hybridization-based PCR-enzyme-linked
      immunosorbent assay for identification of clinically relevant human group A
      rotavirus G and P genotypes.
AB  - A microtiter plate hybridization-based PCR-enzyme-linked immunosorbent assay (PCR
      ELISA) has been used for the detection and identification of a variety of
      microorganisms. Here, we report the development of a PCR-ELISA for the
      identification of clinically relevant human rotavirus VP7 (G1 to G6, G8 to G10,
      and G12) and VP4 (P[4], P[6], P[8], P[9], and P[14]) genotypes. The G and P types
      of reference human and animal rotavirus strains for which specific probes were
      available were correctly identified by the PCR-ELISA. In addition, reference
      strains bearing G or P genotypes for which specific probes were unavailable, such
      as G11, G14, P[3], P[10], and P[11], did not display any cross-reactivity to the
      probes. The usefulness of the assay was further evaluated by analyzing a total of
      396 rotavirus-positive stool samples collected in four countries: Brazil, Ghana,
      Japan, and the United States. The results of this study showed that the PCR-ELISA
      was sensitive and easy to perform without the use of any expensive and
      sophisticated equipment, the reagents used are easy to obtain commercially and
      advantageous over multiplex PCR since more than one type-specific probe is used
      and the selection of probes is more flexible.

PMID- 18057128
TI  - Prediction of cytomegalovirus (CMV) plasma load from evaluation of CMV whole
      blood load in samples from renal transplant recipients.
AB  - In a prospective cohort of 82 renal transplant recipients, we evaluated the
      capacity of the cytomegalovirus (CMV) load in whole blood (WB) to predict the
      plasma CMV load, aiming to identify active CMV infections by using WB samples
      only and to deduce a WB threshold. Using quantitative real-time PCR, a total of
      1,474 WB samples were assayed, of which 279 were positive for CMV, and 140 out of
      the 276 paired plasma samples tested positive. Thirty (36.6%) patients presented
      with at least one positive plasma PCR result, and 21 infection episodes (19
      patients) required curative treatment (median follow-up time, 12 months). When
      the plasma CMV load was >500 copies/ml (n = 70), more than 94% (95% confidence
      interval, 86.0%, 98.4%) of WB samples had >500 copies/ml. Two prediction models
      were built: log(10) plasma viral load (VL) was calculated as -0.3777 + 0.9342 x
      log(10) WB VL and as -0.3777 + 0.8563 x log(10) WB VL for patients with and
      without treatment, respectively. In the validation sample (578 routine samples),
      77.2% of the observed and expected plasma viral loads were concordant (95%
      confidence intervals, 73.5 and 80.5%). According to the model, the plasma viral
      load was >500 copies/ml when the WB load was >3,170 or >4,000 copies/ml in
      patients with or without treatment, respectively. WB seems to be an appropriate
      candidate for routine CMV monitoring of transplant recipients by using a single
      assay.

PMID- 18057129
TI  - Comparison of the BD GeneOhm methicillin-resistant Staphylococcus aureus (MRSA)
      PCR assay to culture by use of BBL CHROMagar MRSA for detection of MRSA in nasal
      surveillance cultures from an at-risk community population.
AB  - We compared the BD GeneOhm methicillin-resistant Staphylococcus aureus (MRSA) PCR
      assay to culture with BBL CHROMagar MRSA for nasal surveillance among 602
      arrestees from the Baltimore City Jail. The sensitivity and specificity were
      88.5% and 91.0%, respectively, and after secondary analysis using enrichment
      broth, they were 89.0% and 91.7%, respectively. Twenty-three of 42 false-positive
      PCR lysates contained methicillin-susceptible S. aureus.

PMID- 18057130
TI  - Molecular characterization of a novel fastidious mycobacterium causing
      lepromatous lesions of the skin, subcutis, cornea, and conjunctiva of cats living
      in Victoria, Australia.
AB  - Between 1999 and 2006, 15 cats were diagnosed with disease attributable to a
      novel mycobacterial species. The infections consisted of granulomatous lesions in
      the skin, subcutis, and ocular or periocular tissues with an indolent but
      progressive clinical course. Lesions typically were found in facial regions or on
      the distal limbs. Cats of all ages and both sexes were affected. Infections often
      were challenging to treat, although they could be cured using surgery in concert
      with combination antimicrobial therapy. Microscopically, lesions were
      granulomatous to pyogranulomatous and contained numerous acid-fast bacilli.
      Scanty cultures of the causal microorganisms occasionally could be obtained in
      mycobacterial broth, but subculture to solid media failed. When cultures were not
      available, DNA was extracted from fresh tissue, lyophilized material, and
      formalin-fixed, paraffin-embedded tissues from lesions. PCR amplification of the
      5' end of the 16S rRNA gene and regions within four additional loci (ITS1, hsp65,
      rpoB, and sodA) was performed with various efficiencies using mycobacterial
      primers. Nucleotide sequences were unique for each locus tested. Nucleotide
      sequences obtained from individual cases were identical for each locus for which
      the amplification was successful. Phylogenetic analysis performed using
      concatenated partial 16S rRNA and hsp65 gene sequences indicated that this novel
      mycobacterial species from Victoria is a member of the Mycobacterium simiae
      related group, taxonomically related to the mycobacterium causing leproid
      granulomas in dogs throughout the world. Based on the clustering of cases, we
      refer to this novel species as Mycobacterium sp. strain Tarwin.

PMID- 18057131
TI  - Association of Mycoplasma ovipneumoniae infection with population-limiting
      respiratory disease in free-ranging Rocky Mountain bighorn sheep (Ovis canadensis
      canadensis).
AB  - Bronchopneumonia is a population-limiting disease in bighorn sheep in much of
      western North America. Previous investigators have isolated diverse bacteria from
      the lungs of affected sheep, but no single bacterial species is consistently
      present, even within single epizootics. We obtained high-quality diagnostic
      specimens from nine pneumonic bighorn sheep in three populations and analyzed the
      bacterial populations present in bronchoalveolar lavage specimens of seven by
      using a culture-independent method (16S rRNA gene amplification and clone library
      analyses). Mycoplasma ovipneumoniae was detected as a predominant member of the
      pneumonic lung flora in lambs with early lesions of bronchopneumonia. Specific
      PCR tests then revealed the consistent presence of M. ovipneumoniae in the lungs
      of pneumonic bighorn sheep in this study, and M. ovipneumoniae was isolated from
      lung specimens of five of the animals. Retrospective application of M.
      ovipneumoniae PCR to DNA extracted from archived formalin-fixed, paraffin
      embedded lung tissues of historical adult bighorn sheep necropsy specimens
      supported the association of this agent with bronchopneumonia (16/34 pneumonic
      versus 0/17 nonpneumonic sheep were PCR positive [P < 0.001]). Similarly, a very
      strong association was observed between the presence of one or more M.
      ovipneumoniae antibody-positive animals and the occurrence of current or recent
      historical bronchopneumonia problems (seropositive animals detected in 9/9 versus
      0/9 pneumonic and nonpneumonic populations, respectively [P < 0.001]). M.
      ovipneumoniae is strongly associated with bronchopneumonia in free-ranging
      bighorn sheep and is a candidate primary etiologic agent for this disease.

PMID- 18057132
TI  - Prediction of methicillin-resistant Staphylococcus aureus involvement in disease
      sites by concomitant nasal sampling.
AB  - Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is
      believed to precede disease. It is therefore reasonable to expect that testing
      for nasal MRSA colonization could provide guidance in the choice of empirical
      therapy for infections. We conducted a retrospective review of 5,779 nasal MRSA
      tests performed within a 24-h period before or after a clinical culture showed
      the growth of any organism. A positive nasal MRSA test strongly predicted MRSA
      involvement at a clinical site (relative risk, 12.9 times higher than in the
      remainder of the population; 95% confidence intervals [CI], 10.4, 16.1). Nasal
      MRSA colonization also strongly predicted antimicrobial resistance in other
      organisms. A negative nasal test was less useful; only 217 of 323 patients
      (67.2%; 95% CI, 61.8, 72.3) with clinical cultures involving MRSA had detectable,
      concomitant nasal MRSA colonization. Patients with clindamycin-susceptible MRSA
      infections were less likely (59%) to have nasal colonization than those with
      clindamycin-resistant MRSA infections (71%; P = 0.042). Patients nasally
      colonized with MRSA were substantially more likely to have antibiotic-resistant
      floras in clinical specimens, and this should be considered when initiating
      therapy. However, nearly a third of MRSA-infected patients were not nasally
      colonized, suggesting that nasal colonization need not precede disease and that a
      negative test for nasal colonization would not rule out MRSA disease in settings
      of moderate or high prevalence.

PMID- 18057133
TI  - The microbicide tenofovir does not inhibit nucleic acid amplification tests for
      detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine samples.
AB  - The potential inhibitory effects of tenofovir and a placebo were examined using
      the Becton Dickinson ProbeTec, Gen-Probe Aptima Combo 2, and Roche Amplicor tests
      to detect Chlamydia trachomatis and Neisseria gonorrhoeae. Concentrations of 5%
      to 0% of tenofovir and the placebo were added to dilutions of C. trachomatis and
      N. gonorrhoeae. No appreciable inhibition was observed.

PMID- 18057134
TI  - Virulence factors in urinary Escherichia coli strains: phylogenetic background
      and quinolone and fluoroquinolone resistance.
AB  - Quinolone- and fluoroquinolone-resistant Escherichia coli strains harbor fewer
      virulence factors than susceptible strains. The reasons underlying this
      correlation are incompletely understood. We investigated the phylogenetic
      background, the presence of the papC, hlyA, and cnf1 (pathogenicity island
      II(J96)-associated), fimA, iss, and iutA genes, and the presence of type 1
      fimbriae, P fimbriae, and hemolysin in 243 urinary E. coli isolates resistant
      only to quinolones (8%), resistant to both quinolones and fluoroquinolones (51%),
      or susceptible to both drugs (41%). Group B2 accounted for 56% of the isolates,
      showing a significantly higher prevalence among fluoroquinolone-susceptible
      strains than among resistant strains (65% versus 50% [P = 0.03]). hly and cnf1
      were significantly more associated with susceptibility (P < 0.001) and with group
      B2 (P < 0.001 for group B2 versus groups A and D). However, within group B2,
      fluoroquinolone-resistant strains showed lower prevalences of papC, hlyA, and
      cnf1 than their susceptible counterparts (P < 0.001). In contrast, the incidence
      of iutA appeared higher for refractory isolates, including group B2, than for
      susceptible isolates (P < 0.001). Only in group B2 did fluoroquinolone-resistant
      strains reveal a lesser ability to agglutinate Saccharomyces cerevisiae (7%) than
      quinolone-resistant (87%) and susceptible (80%) isolates, despite uniform
      possession of fimA genes. No similar contrast emerged for expression of hemolysin
      and P fimbriae. Mutations conferring quinolone and fluoroquinolone resistance may
      thus require a particular genetic background, not strictly correlated with
      phylogenetic groups. More interestingly, the mutational event itself can affect
      the expression of type 1 fimbriae, at least in the prevalent and complex B2
      strains.

PMID- 18057135
TI  - Development of a species-specific fur gene-based method for identification of the
      Burkholderia cepacia complex.
AB  - Burkholderia is an important bacterial genus with a complex taxonomy that
      contains species of both ecological and pathogenic importance, including nine
      closely related species collectively termed the Burkholderia cepacia complex
      (BCC). Unfortunately, 16S rRNA gene analysis has proven to be not sensitive
      enough to discriminate between species of the BCC. Alternative species
      identification strategies such as recA-based PCR followed by restriction fragment
      length polymorphism analysis, although initially useful, have proven to be
      inaccurate with the increasing species diversity of the BCC. recA gene sequence
      analysis is more discriminatory and corroborates other biochemical and polyphasic
      means of taxonomic differentiation. However, it is limited by the fact that
      certain BCC species are subdivided into discrete recA sequence subgroups that may
      confuse clinical diagnoses. In this study, an effective approach is described for
      the rapid differentiation of BCC species from both environmental and clinical
      sources by means of a single-locus sequencing and PCR assay using fur as a target
      gene that provides sequence phylogenies that are species specific and, with few
      exceptions, not divided into subspecies clusters. This assay is specific and can
      be used to correctly determine the species status of BCC strains tested following
      sequencing and amplification of the fur gene by both general and species-specific
      primers. Based on our results, this typing strategy is simpler than and as
      sensitive as established tests currently in use clinically. This assay is useful
      for the rapid, definitive identification of all nine current BCC species and
      potentially novel species groups.

PMID- 18057137
TI  - Molecular characterization of three new virulent Newcastle disease virus variants
      isolated in China.
AB  - Three cases of Newcastle disease virus (NDV) found in nature had the lentogenic
      motif (112)G-R-Q-G-R-L(117) in their fusion protein cleavage sites. However, both
      intracerebral pathogenicity and intravenous pathogenicity indexes showed that
      these NDV isolates were virulent. In comparison with the LaSota live virus
      vaccine, these viruses had significant genetic variations in the hemagglutinin
      neuraminidase gene.

PMID- 18057136
TI  - Real-time reverse transcription-PCR assay for comprehensive detection of human
      rhinoviruses.
AB  - Human rhinoviruses (HRVs) are important contributors to respiratory disease, but
      their healthcare burden remains unclear, primarily because of the lack of
      sensitive, accurate, and convenient means of determining their causal role. To
      address this, we developed and clinically validated the sensitivity and
      specificity of a real-time reverse transcription-PCR (RT-PCR) assay targeting the
      viral 5' noncoding region defined by sequences obtained from all 100 currently
      recognized HRV prototype strains and 85 recently circulating field isolates. The
      assay successfully amplified all HRVs tested and could reproducibly detect 50 HRV
      RNA transcript copies, with a dynamic range of over 7 logs. In contrast, a
      quantified RNA transcript of human enterovirus 68 (HEV68) that showed the
      greatest sequence homology to the HRV primers and probe set was not detected
      below a concentration of 5 x 10(5) copies per reaction. Nucleic acid extracts of
      111 coded respiratory specimens that were culture positive for HRV or HEV were
      tested with the HRV real-time RT-PCR assay and by two independent laboratories
      that used different in-house HRV/HEV RT-PCR assays. Eighty-seven HRV-culture
      positive specimens were correctly identified by the real-time RT-PCR assay, and 4
      of the 24 HEV-positive samples were positive for HRV. HRV-specific sequences
      subsequently were identified in these four specimens, suggesting HRV/HEV
      coinfection in these patients. The assay was successfully applied in an
      investigation of a coincidental outbreak of HRV respiratory illness among
      laboratory staff.

PMID- 18057138
TI  - Gardnerella vaginalis bacteremia in a previously healthy man: case report and
      characterization of the isolate.
AB  - Gardnerella vaginalis in women causes vaginitis or infections in other sites,
      such as the urinary tract, but is an infrequent cause of bacteremia. Bacteremia
      in men is very rare and is typically associated with immunocompromised states.
      Here we describe G. vaginalis bacteremia in a previously healthy man with renal
      calculi and urosepsis.

PMID- 18057141
TI  - PEDS: developmental milestones--an accurate brief tool for surveillance and
      screening.
AB  - About 16% of children have developmental-behavioral disabilities but less than
      one-third of the children are detected by their health care providers, probably
      because of the use of informal milestones checklists. The goal of this study is
      to determine the reliability, validity, accuracy, and utility of a new tool,
      PEDS: Developmental Milestones (PEDS:DM). Data from a nationally representative
      sample of 1619 children administered developmental diagnostic measures were mined
      for items that best predicted performance in each developmental domain. A total
      of 112 met inclusion criteria, that is, sensitivity/specificity > or = 70%. For
      each domain/age level (birth to 8 years of age), sensitivity to performance less
      than or equal to the 16th percentile on diagnostic measures was 83% and
      specificity was 84%. Reliability was high (test-retest, .98 to .99; interrater,
      .82 to .96; kappa, .81). The readability level was 1.8 grades (range 1.1 to 2.6).
      The PEDS:DM appears to be a validated, accurate alternative to informal
      milestones checklists that are a probable contributor to underdetection of
      children with delays and disabilities.

PMID- 18057142
TI  - Common/Unity: an innovative program to address 3 root causes of many of the
      social ills seen in adolescents.
AB  - Multiple community agencies coordinated their individual expertise to develop a
      comprehensive program for a planned community in a 24-apartment complex for
      single, young (age range, 18-21 years), homeless mothers and their infants and
      children. Although objective evaluation of the program proved difficult,
      "community" was established and lives were changed. The program was designed to
      address multiple issues faced by teenaged mothers but did not directly address
      critical factors of youths' internal motivation and decision-making processes.
      Attempting to reverse major impediments in the lives of young mothers with
      histories of violence, abuse, unstable early home environments, and lack of
      education while assuming the sole responsibility of raising a child, advancing
      their education, and maintaining employment is a daunting task, but a task that
      deserves our urgent attention.

PMID- 18057143
TI  - Infections and apparent life-threatening events.
AB  - The need for routine sepsis evaluation in patients who have experienced an
      apparent life-threatening event but lack signs of infection remains
      controversial. To assess their risk of a serious occult bacterial infection,
      records were reviewed of 95 infants in whom infections were discovered during
      their inpatient evaluation after an apparent life-threatening event. Noted for
      each patient was the presence of any suggestive findings that would have prompted
      a physician to consider the given type of infection in the differential
      diagnosis. Thirty patients had bacterial infections; all but 5 had suggestive
      findings. The exceptions included 1 patient with pneumonia and 4 with urinary
      tract infections. None of the remaining 25 patients had occult bacterial
      infections. In patients with an apparent life-threatening event who appear well
      and lack signs suggestive of a serious bacterial infection, it may be possible to
      forego routine sepsis evaluation beyond a chest radiograph and urine culture
      without risking a serious missed diagnosis.

PMID- 18057144
TI  - Neonatal hyperbilirubinemia: an unexpected cause.
AB  - Hyperbilirubinemia is a common cause for newborn hospital admission. Although the
      cause of hyperbilirubinemia is usually benign and self-limited, there is always a
      large differential diagnosis. Atypical presenting signs and symptoms, such as
      significant anemia or bleeding, should encourage further evaluation for
      underlying disorders, such as inherited coagulation defects. This article
      describes the case of a 5-day-old infant who presented to the emergency
      department with hyperbilirubinemia, anemia, and ecchymoses from birth trauma. His
      hospital course is described, along with a review on the background, evaluation,
      management, and complications of hemophilia A.

PMID- 18057145
TI  - Factor XIII deficiency: a differential diagnosis to be considered in suspected
      nonaccidental injury presenting with intracranial hemorrhage.

PMID- 18057147
TI  - Stepwise approach to topical therapy for atopic dermatitis.

PMID- 18057148
TI  - Biologic and chemical terrorism in children: an assessment of residents'
      knowledge.
AB  - This study was conducted to determine the baseline fund of knowledge of pediatric
      and emergency medicine residents at a single institution in the medical
      management of pediatric victims of biologic and chemical terrorism. A test
      covering essential content was developed and validated by experts. The test was
      given anonymously to volunteer pediatric and emergency medicine residents at a
      single institution. The test was readministered 5 months after a lecture on the
      content. The 34 pediatric residents and 15 emergency medicine residents scored a
      median of 65% and 73%, respectively (P = .03). Residents from both specialties
      combined scored a median of 70% correct versus those residents who did not attend
      the lecture. Pediatric and emergency medicine residents are significantly
      unprepared to manage pediatric victims of biologic and chemical terrorism.
      Education curriculums on this topic must be incorporated into these residencies.
      The traditional lecture format may not be the most effective technique.

PMID- 18057149
TI  - Institutional availability of fertility preservation.

PMID- 18057146
TI  - Diagnosis and management of common dermatoses in children: atopic, seborrheic,
      and contact dermatitis.
AB  - Atopic, seborrheic, and contact dermatitis can significantly reduce the quality
      of life of patients and their families. Although differing in specific aspects of
      their epidemiology, etiology, and pathobiology, all 3 dermatoses are common in
      the pediatric population, and they share a common treatment approach. Although
      effective and widely used to manage exacerbations of pediatric dermatitis, the
      use of topical corticosteroid remains a concern for some physicians and parents
      because of its potential for systemic absorption and adverse events associated
      with prolonged use. Newer additions to the dermatitis treatment algorithm, such
      as the topical calcineurin inhibitors, may provide an effective steroid-sparing
      treatment option. Adjuvant treatments, such as antihistamines, antifungals, and
      antibiotics, also can provide benefit in appropriate circumstances. As there is
      no cure for dermatitis, a comprehensive, multipronged management strategy of
      preventive measures, such as trigger avoidance and periodic pharmacologic
      treatment, will provide patients and caregivers with the best opportunity to
      successfully control the disease.

PMID- 18057150
TI  - Subcutaneous granuloma annulare in a child: a case report.

PMID- 18057139
TI  - What can we learn from rodents about prolactin in humans?
AB  - Prolactin (PRL) is a 23-kDa protein hormone that binds to a single-span membrane
      receptor, a member of the cytokine receptor superfamily, and exerts its action
      via several interacting signaling pathways. PRL is a multifunctional hormone that
      affects multiple reproductive and metabolic functions and is also involved in
      tumorigenicity. In addition to being a classical pituitary hormone, PRL in humans
      is produced by many tissues throughout the body where it acts as a cytokine. The
      objective of this review is to compare and contrast multiple aspects of PRL, from
      structure to regulation, and from physiology to pathology in rats, mice, and
      humans. At each juncture, questions are raised whether, or to what extent, data
      from rodents are relevant to PRL homeostasis in humans. Most current knowledge on
      PRL has been obtained from studies with rats and, more recently, from the use of
      transgenic mice. Although this information is indispensable for understanding PRL
      in human health and disease, there is sufficient disparity in the control of the
      production, distribution, and physiological functions of PRL among these species
      to warrant careful and judicial extrapolation to humans.

PMID- 18057151
TI  - Why parents seek medical evaluations for their children with mild acute
      illnesses.
AB  - The reasons underlying parents' decisions to seek medical evaluations for their
      mildly ill children are not well understood. This cross-sectional study tracked
      parents' requests for on-site medical evaluations at a sick child care program. A
      logistic regression model identified factors associated with parents' decisions
      to seek medical evaluations for their children based on the data from parent
      completed questionnaires. A convenience sample of 196 parents completed all
      questionnaires; 62 (31.6%) parents sought medical evaluations. Parents were more
      likely to seek medical evaluations if they were concerned about missing work
      (odds ratio = 8.6; 95% confidence interval, 3.3-22.0; P = .0001), if they smoked
      (odds ratio = 3.7; 95% confidence interval, 1.1-12.4; P = .037), or if their
      spouse's highest educational attainment was some high school (odds ratio = 0.4;
      95% confidence interval, 0.1-1.0; P = .044). The data highlight the problems
      working parents have in accessing health care during usual working hours and the
      potential value of convenient health care programs.

PMID- 18057152
TI  - X-linked hypophosphatemic rickets associated with respiratory failure.
AB  - We report a 5-year-old girl who presented to our emergency room with respiratory
      arrest and limb deformities and was subsequently diagnosed with X-linked
      hypophosphatemic rickets. On normalization of the serum phosphorus concentration,
      her respiratory distress resolved, illustrating that untreated X-linked
      hypophosphatemic rickets can lead to life-threatening respiratory distress.

PMID- 18057140
TI  - Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation
      of bone remodeling in health and disease.
AB  - Osteoclasts and osteoblasts dictate skeletal mass, structure, and strength via
      their respective roles in resorbing and forming bone. Bone remodeling is a
      spatially coordinated lifelong process whereby old bone is removed by osteoclasts
      and replaced by bone-forming osteoblasts. The refilling of resorption cavities is
      incomplete in many pathological states, which leads to a net loss of bone mass
      with each remodeling cycle. Postmenopausal osteoporosis and other conditions are
      associated with an increased rate of bone remodeling, which leads to accelerated
      bone loss and increased risk of fracture. Bone resorption is dependent on a
      cytokine known as RANKL (receptor activator of nuclear factor kappaB ligand), a
      TNF family member that is essential for osteoclast formation, activity, and
      survival in normal and pathological states of bone remodeling. The catabolic
      effects of RANKL are prevented by osteoprotegerin (OPG), a TNF receptor family
      member that binds RANKL and thereby prevents activation of its single cognate
      receptor called RANK. Osteoclast activity is likely to depend, at least in part,
      on the relative balance of RANKL and OPG. Studies in numerous animal models of
      bone disease show that RANKL inhibition leads to marked suppression of bone
      resorption and increases in cortical and cancellous bone volume, density, and
      strength. RANKL inhibitors also prevent focal bone loss that occurs in animal
      models of rheumatoid arthritis and bone metastasis. Clinical trials are exploring
      the effects of denosumab, a fully human anti-RANKL antibody, on bone loss in
      patients with osteoporosis, bone metastasis, myeloma, and rheumatoid arthritis.

PMID- 18057153
TI  - Freckling 11 years after pulsed dye laser therapy for an infantile hemangioma:
      coincidence or a previously unrecognized complication?
AB  - A case of asymmetric freckling on the cheeks of a child who 11 years earlier
      received pulsed dye laser treatment for a hemangioma on the right cheek was
      recently evaluated. Only the lasered areas of the face (her cheeks) demonstrated
      asymmetric freckling, whereas the unlasered areas of the face such as the nose
      demonstrated typical, normal, symmetric freckling. No explanation, such as
      asymmetric sun exposure or sunscreen administration, could be elicited by
      detailed history. The authors suggest that the asymmetric freckling on the
      patient's cheeks might represent a previously unrecognized complication of pulsed
      dye laser.

PMID- 18057154
TI  - Childhood epilepsy with occipital paroxysms: variations on the theme.
AB  - This review reports on the various presentations as well as new revealed data
      relating to the epileptic disorder defined as childhood epilepsy with occipital
      paroxysms characterized by occipital epileptic discharges recorded by
      electroencephalography. The initial rigidly delineated subtypes by the
      International League Against Epilepsy included the following: (a) Panayiotopoulos
      syndrome-early-onset seizure disorder presenting with prolonged infrequent,
      nocturnal autonomic seizures, accompanied by eye deviation and ictal vomiting.
      (b) Gastaut syndrome-late-onset type presenting with short diurnal frequent
      seizures and visual ictal manifestations along with migrainous headaches. A high
      percentage of children present, however, with mixed clinical phenomena making it
      difficult to comply with the rigidly segregated syndromes reported by several
      authorities including our recent report on 28 children of whom 14 showed mixed
      phenomena. Therefore, childhood epilepsy with occipital paroxysm should be
      suspected at any age presenting with nocturnal vomiting, autonomic impairment,
      focal motor fits with head deviation, migraine headaches, and/or visual
      perturbations.

PMID- 18057155
TI  - W(h)ither adolescent medicine? Time to fish or cut bait.

PMID- 18057156
TI  - Atypical presentations of celiac disease: recurrent intussusception and
      pneumatosis intestinalis.

PMID- 18057157
TI  - Gynecomastia and hypogonadism.

PMID- 18057158
TI  - Spontaneous drainage of neonatal cephalohematoma: a delayed complication of scalp
      abscess.
AB  - Neonatal cephalohematomas are known complications of traumatic deliveries, and
      the majority of cases resolve without intervention. Scalp abscesses are rare and
      often described as benign complications of fetal scalp monitoring. Spontaneous
      drainage of a neonatal cephalohematoma, with or without associated scalp abscess,
      has not yet been described. We present a case of a neonate with recurrent
      Escherichia coli bacteremia and spontaneous drainage of a large cephalohematoma
      through an overlying scalp abscess.

PMID- 18057159
TI  - Infants born to mothers with anti-SSA/Ro autoantibodies: neonatal outcome and
      follow-up.
AB  - Neonatal lupus syndrome is considered a model of passively acquired autoimmune
      disease. The first 10 newborns born to mothers with connective tissue disease and
      positive for anti-SSA/Ro antibodies enrolled in a follow-up program to evaluate
      the incidence of cardiac, hepatobiliary, hematologic, echoencephalographic, and
      cutaneous manifestations until 9 months of age are described in this study. No
      congenital heart block was observed, but only transient rhythm alterations were
      observed. In all, 1 infant showed typical neonatal lupus syndrome skin lesions at
      3 months of age. During the neonatal period, echoencephalographic alterations
      were found more frequently, whereas at follow-up, hepatic and hematologic
      alterations were more often observed. In all, 1 baby showed persistent
      neutropenia. A standard program that enrolls all infants born to mothers with
      anti-SSA/Ro autoantibodies, who are at risk of developing neonatal lupus
      syndrome, should also include tests performed some time after birth, as a number
      of clinical manifestations might appear at a late stage.

PMID- 18057160
TI  - What factors are important for pediatric residents' smoking cessation counseling
      of parents?
AB  - Pediatricians are expected to discuss the hazards of passive smoking and provide
      smoking cessation counseling (SCC) because passive smoking is known to have a
      direct negative effect on children's health. We conducted a cross-sectional
      survey of pediatric and medicine- pediatric residents at 2 training programs to
      identify resident-reported factors associated with higher confidence in and
      frequency of SCC. In this sample of 71 residents, 83% reported asking about
      parental smoking but only 36% reported counseling parents to quit smoking.
      Knowledge of smoking cessation resources was the factor most strongly associated
      with high confidence in and frequency of SCC. Research should be done to evaluate
      if improving awareness of smoking cessation resources for parents improves
      pediatricians' confidence in asking about parental smoking and the likelihood of
      advising parents to quit smoking.

PMID- 18057161
TI  - Failure-to-thrive in an infant following injection of capillary hemangioma with
      triamcinolone acetonide.

PMID- 18057162
TI  - An analysis of deaths in portable cribs and playpens: what can be learned?
AB  - To assess the risk of using portable cribs and playpens as sleep surfaces for
      infants, data from playpen/portable crib deaths occurring between January 1,
      1999, and February 4, 2004, that were reported to the Consumer Product Safety
      Commission were retrospectively reviewed. Twenty-one playpen/portable crib deaths
      were identified. Two-thirds of the deaths were in infants. Asphyxia, positional
      asphyxia, and suffocation were the leading causes of death. Several deaths were
      the consequence of risks unique to playpens and portable cribs: playpen collapse,
      modifications to the playpen, and improper assembly. The data demonstrate some
      unique risks posed by playpens/portable cribs, including risks from improper
      assembly and setup. Programs recommending and using playpens/portable cribs as
      routine infant sleep surfaces must be aware of the need for additional guidance
      regarding use of playpens/portable cribs.

PMID- 18057163
TI  - How should immunization rates be measured in the office setting? A study from
      PROS and NMA PedsNet.
AB  - The aim of the study was to compare the validity and reliability of 2 sampling
      methods for measuring immunization rates to a reference standard in a national
      sample of pediatric office practices. The consecutive method involved patients
      seen consecutively in the office for any reason; the random record was a random
      selection of medical records; and the reference standard active method, data of a
      randomly selected subgroup of children in the random record survey were
      supplemented with information from a telephone interview. The consecutive method
      of assessing immunization rates results in rates that are, on average, higher and
      closer to the reference standard, but also more variable. The random record
      method rates are lower and further from the study reference standard compared
      with the consecutive method, but more precise. The consecutive method for
      measuring practice immunization rates could be a useful quality improvement tool
      as practices seek to improve immunization delivery and quality of care. It is
      inexpensive, simple, and easy to implement.

PMID- 18057164
TI  - A nonoperative treatment technique for peroneal tendon subluxation.

PMID- 18057165
TI  - Dermatological clue to diagnosis of Degos disease in a 2-year-old with obscure
      chronic abdominal pain.

PMID- 18057166
TI  - The risk of antimalarials in patients with renal failure.
AB  - We present here a patient with end stage renal failure who received two weeks
      antimalarial prophylaxis at full dose leading to life threatening toxicity with
      severe acute megaloblastic anaemia, symptomatic pancytopenia and exfoliative
      dermatitis. Prompt recognition and treatment can rapidly reverse these fatal
      effects but more importantly, education of patients before travel is imperative
      in preventing such events.

PMID- 18057167
TI  - Diversifying the options for interacting with patients.

PMID- 18057168
TI  - Non-invasive treatment of ST elevation myocardial infarction.
AB  - There is good evidence that timely restoration of coronary blood flow in
      obstructed infarct related arteries is a significant determinant of both short
      and long term mortality and morbidity. This is irrespective of whether it is
      achieved using fibrinolytic therapy or percutaneous coronary intervention (PCI).
      Despite the clear advantages of primary PCI, it is thrombolysis that remains the
      main reperfusion strategy in the UK. Recent data have highlighted mortality
      benefits when antiplatelet treatment and anticoagulation are used as adjuncts to
      thrombolysis. Moreover, of those who receive thrombolysis, 60% proceed to
      coronary arteriography within 6 months of their index event. Recent studies have
      been published clarifying the timing of coronary arteriography in patients who
      receive thrombolysis as reperfusion therapy.

PMID- 18057169
TI  - Gene therapy in head and neck cancer: a review.
AB  - Gene therapy for cancer is a rapidly evolving field with head and neck squamous
      cell cancer being one of the more frequently targeted cancer types. The number of
      clinical trials in the UK is growing and there is already a commercially
      available agent in China. Various gene therapy strategies along with delivery
      mechanisms for targeting head and neck cancer are reviewed.

PMID- 18057170
TI  - Early structured core training of junior trainees in ophthalmology.
AB  - The implementation of modernizing medical careers (MMC) has resulted in some
      specialties being allocated very inexperienced trainees such as ophthalmology. We
      aim to describe the process of implementation of MMC and how it may affect the
      service provision in smaller specialities such as ophthalmology. A methodical
      approach in a district hospital setting was used to provide early core training
      to such trainees involving managerial support. The quality of service provided by
      newer trainees can be enhanced by providing early structured training during
      induction to create an atmosphere of enthusiasm and continued learning. This
      example can be used in other units and specialties.

PMID- 18057172
TI  - Pathological fracture of the talar neck associated with amyloid deposition.

PMID- 18057171
TI  - Liver disease in erythropoietic protoporphyria: insights and implications for
      management.

PMID- 18057173
TI  - Surveillance of patients post-endovascular aneurysm repair.
AB  - Endovascular aneurysm repair (EVAR) is increasingly being employed as an
      alternative to open surgical repair for patients with abdominal aortic aneurysms.
      The surveillance of patients post-EVAR has traditionally been carried out with
      regular computed tomographic scans which have in part been responsible for the
      high costs associated with this procedure. Duplex has been proposed as an
      alternative, but researchers have so far been unable to devise a standardised
      protocol for this surveillance. This review aims to provide a clear understanding
      of currently employed imaging modalities and discuss future surveillance
      possibilities for this patient group.

PMID- 18057174
TI  - What's being used to spike your drink? Alleged spiked drink cases in inner city
      London.
AB  - OBJECTIVES: To determine the incidence and character of drink spiking in an urban
      population of patients within the UK presenting to an emergency department
      concerned they had consumed a deliberately contaminated drink. STUDY DESIGN:
      Prospective case series determining the presence and quantity of sedative and
      illicit drugs, and ethanol in biological samples (blood and urine) obtained from
      consenting patients >18 years of age presenting to a large inner city London
      emergency department alleging they had consumed a spiked drink within the
      previous 12 h. RESULTS: Biological samples were obtained from 67 (blood) and 75
      (urine) of 78 study participants. 82% of participants were female, mean age 24
      years. Mean time from alleged exposure to biological sampling was 5.9 h (range 1
      12 h). Ethanol was detected in 89.7% of participants. Mean serum ethanol
      concentration was 1.65 g/l (range 0.04-3.1 g/l); 60% of participants had a serum
      ethanol concentration associated with significant intoxication (>1.5 g/l).
      Illicit drugs were detected in 12 (15%) participants; 7 denied intentional
      exposure (3 methylenedioxymethamphetamine, 3 cannabis, 1 gamma-hydroxybutyrate).
      Medicinal drugs were detected in 13 participants; only 1 exposure was unexplained
      (benzodiazepine). Overall illicit or medicinal drugs of unexplained origin were
      detected in 8 (10%) participants. Unexplained sedative drug exposure was detected
      in only 2 (3%) participants. CONCLUSIONS: Use of sedative drugs to spike drinks
      may not be as common as reported in the mainstream media. A large number of study
      participants had serum ethanol concentrations associated with significant
      intoxication; the source (personal over-consumption or deliberate drink spiking)
      is unclear.

PMID- 18057175
TI  - Web 2.0 technologies for undergraduate and postgraduate medical education: an
      online survey.
AB  - OBJECTIVES: To identify the current familiarity and use of Web 2.0 technologies
      by medical students and qualified medical practitioners, and to identify the
      barriers to its use for medical education. METHODS: A semi-structured online
      questionnaire survey of 3000 medical students and 3000 qualified medical
      practitioners (consultants, general practitioners and doctors in training) on the
      British Medical Association's membership database. RESULTS: All groups had high
      familiarity, but low use, of podcasts. Ownership of digital media players was
      higher among medical students. There was high familiarity, but low use, of other
      Web 2.0 technologies except for high use of instant messaging and social
      networking by medical students. All groups stated that they were interested in
      using Web 2.0 technologies for education but there was lack of knowledge and
      skills in how to use these new technologies. CONCLUSIONS: There is an overall
      high awareness of a range of new Web 2.0 technologies by both medical students
      and qualified medical practitioners and high interest in its use for medical
      education. However, the potential of Web 2.0 technologies for undergraduate and
      postgraduate medical education will only be achieved if there is increased
      training in how to use this new approach.

PMID- 18057176
TI  - Polymorbidity in diabetes in older people: consequences for care and vocational
      training.
AB  - OBJECTIVE: To investigate the prevalence of complicating and concurrent
      morbidities in older diabetic patients and to evaluate to what extent their
      occurrence affects the burden of disease and use of medical healthcare. STUDY
      DESIGN: Cross-sectional analysis of retrospectively obtained data on
      comorbidities and use of medical healthcare. Healthcare registration systems were
      used to retrieve data on 300 patients with diabetes aged >or=60 years who,
      according to the severity of their disease and intensity of care required, were
      treated in a regional general practitioner (GP), diabetes nurse specialist (DNS)
      or medical specialist (MS) practice. RESULTS: Complicating and concurrent
      morbidities were often found irrespective of the type of practice involved. After
      adjustments for differences in sex, age and glycosylated haemoglobin (HbA1c), the
      extent of complicating comorbidities showed sequential increases in patients
      managed by GP, DNS and MS (mean number of 3.6, 4.7 and 6.7, respectively;
      p(trend)<0.001). However, the mean number of concurrent comorbidities was similar
      across all three settings (2.1, 1.8 and 2.0, respectively). Both complicating and
      concurrent comorbidities were similarly associated with the extent of drug use
      (beta = 0.49 (95% CI 0.40 to 0.58) and beta = 0.57 (95% CI 0.52 to 0.72),
      respectively) and the number of consultations with specialists other than the
      main care giver (beta = 1.19 (95% CI 1.15 to 1.24) and beta = 1.21 (95% CI 1.14
      to 1.28), respectively). However, the mean number of different specialists
      involved in a patient's care per additional concurrent comorbidity was twice as
      high as per any additional complicating comorbidity (beta = 0.60 (95% CI 0.48 to
      0.71) vs beta = 0.31 (95% CI 0.24 to 0.39)). CONCLUSIONS: The use of healthcare
      facilities by older patients with diabetes is substantial, irrespective of the
      complexity of the disease and the kind of practice involved. The common
      manifestation of complicating and concurrent comorbidities and their varying
      complexity in individual patients requires a patient-oriented rather than a
      disease-oriented approach and vocational training programmes for care givers that
      are tailored to the complexity of multiple chronic diseases.

PMID- 18057177
TI  - Evaluation of the need for endoscopy to identify low-risk patients presenting
      with an acute upper gastrointestinal bleed suitable for early discharge.
AB  - AIMS: To audit the safety of differing protocol-driven early-discharge policies,
      from two sites, for low-risk acute upper gastrointestinal (GI) bleeding and
      determine if default early (<24 h) in-patient endoscopy is necessary. METHODS:
      All patients with low-risk acute upper GI bleeding presenting to two separate
      hospital sites in Leeds from August 2002 to March 2005 were identified. Both
      hospitals operate nurse-led process-driven protocols for discharge within 24 h,
      but only one includes default endoscopy. Relevant information was obtained from
      patients' notes, patient administration systems, discharge letters and endoscopy
      records. RESULTS: 120 patients were admitted to site A and 74 to site B. Median
      length of stay on the clinical decisions unit was 12.6 h at site A and 9.4 h at
      site B (p = 0.045). Oesophagogastroduodenoscopy was performed on 89/120 (74%)
      patients at site A compared with only 7/74 (9%) at site B (p<0.001). Six of 120
      (5%) patients from site A were admitted to hospital for further observation
      compared with 6/74 (8%) from site B (p = 0.38). Of the remaining patients, all
      were discharged within 24 h, and 8/114 (7%) at site A vs 17/68 (25%) at site B
      were given hospital clinic follow-up (p<0.001). None of the 194 patients had
      further bleeding or complications within 30 days. CONCLUSIONS: Patients admitted
      with a low-risk acute upper GI bleeding can be managed safely by a nurse-led
      process-driven protocol, based on readily available clinical and laboratory
      variables, with early discharge <24 h. Avoiding in-patient endoscopy appears to
      be safe but at the price of greater clinic follow-up.

PMID- 18057178
TI  - Biliary tract infection and bacteraemia: presentation, structural abnormalities,
      causative organisms and clinical outcomes.
AB  - BACKGROUND: Biliary tract infection is a common cause of bacteraemia and is
      associated with high morbidity and mortality. Few papers describe blood culture
      isolates, underlying structural abnormalities and clinical outcomes in patients
      with bacteraemia. AIMS: To determine the proportion of bacteraemias caused by
      biliary tract infection and to describe patient demographics, underlying
      structural abnormalities and clinical outcomes in patients with bacteraemia.
      DESIGN: Prospective cohort study. METHODS: Biliary tract infection that caused
      bacteraemia was defined as a compatible clinical syndrome and a blood culture
      isolate consistent with ascending cholangitis. Patients aged 16 years and over
      were included in the study. From June 2003 to May 2005, demographic and clinical
      data were collected prospectively on all adult patients with bacteraemia.
      Radiological and endoscopic retrograde cholangiopancreatography findings were
      collected retrospectively. RESULTS: In 49 patients, the biliary tract was the
      site of infection for 39/592 (6.6%) community-acquired and 19/466 (4.1%) hospital
      acquired episodes of bacteraemia. Three patients had mixed bacteraemias, and four
      had recurrent bacteraemia. The proportion of patients presenting with a
      structural abnormality was 34/49 (69%), and, of these structural abnormalities,
      18/34 (53%) were pre-existing or newly diagnosed malignancies. Gram-negative
      organisms caused 55/58 (95%) episodes of bacteraemia. The most common Gram
      negative organisms were Escherichia coli (34/55; 62%) and Klebsiella pneumoniae
      (14/55; 26%). Of the E coli isolates, 6/34 (18%) were extended spectrum beta
      lactamase producers or multiply drug resistant. Thirty-day mortality was 7/49
      (14%). There was no difference in time taken to administer an effective
      antibiotic to survivors and non-survivors (0.86 vs 1.05 days, respectively, p =
      0.92). Of the seven who died, four died from septic shock within 48 h of
      admission caused by "susceptible" Gram-negative organisms. Two others died from
      disseminated malignancy. CONCLUSIONS: The proportion of bacteraemias caused by
      biliary tract infection was 5.5%. The most common infecting organisms were E coli
      and K pneumoniae. There was a strong association with choledocholithiasis and
      malignancies, both pre-existing and newly diagnosed. Death was uncommon but when
      it occurred was often caused by septic shock within 48 h of presentation.

PMID- 18057179
TI  - Learning curves in surgical practice.
AB  - Learning curves are often referred to in the context of medical education and
      training, though their trajectories and natures are a matter of debate. The
      origins of this concept derive from industry and its relevance to contemporary
      medicine and surgery remains controversial. We describe the history, derivation,
      character and possible mechanisms to deal with the implications of learning
      curves in the current climate of clinical governance and modernizing medical
      careers.

PMID- 18057180
TI  - Development and validation of a cell-based high-throughput screening assay for
      TRPM2 channel modulators.
AB  - TRPM2 is a member of the transient receptor potential melastatin (TRPM)-related
      ion channel family. The activation of TRPM2 induced by oxidative/nitrosative
      stress leads to an increase in intracellular free Ca(2+). Although further
      progress in understanding TRPM2's role in cell and organism physiology would be
      facilitated by isolation of compounds able to specifically modulate its function
      in primary cells or animal models, no cell-based assays for TRPM2 function well
      suited for high-throughput screening have yet been described. Here, a novel
      suspension B lymphocyte cell line stably expressing TRPM2 was used to develop a
      cell-based assay. The assay uses the Ca(2+)-sensitive fluorescence dye, Fluo-4 NW
      (no wash), to measure TRPM2-dependent Ca(2+) transients induced by H(2)O(2) and N
      methyl-N'-nitrosoguanidine in a 96-well plate format. Assay performance was
      evaluated by statistical analysis of the Z' factor value and was consistently
      greater than 0.5 under optimal conditions, suggesting that the assay is very
      robust. For assay validation, the effects of known inhibitors of TRPM2 and TRPM2
      gating secondary messenger production were determined. Overall, the authors have
      developed a cell-based assay that may be used to identify TRPM2 ion channel
      modulators from large compound libraries.

PMID- 18057182
TI  - Induction of antitumor acquired immunity by baculovirus Autographa californica
      multiple nuclear polyhedrosis virus infection in mice.
AB  - The baculovirus Autographa californica multiple nuclear polyhedrosis virus
      (AcMNPV) has been studied as a gene therapy vector. Here, we demonstrated that
      AcMNPV induces antitumor acquired immunity. These results suggest that AcMNPV has
      the potential to be an efficient virus or tumor therapy agent which induces
      innate and acquired immunity.

PMID- 18057181
TI  - A novel, killed-virus nasal vaccinia virus vaccine.
AB  - Live-virus vaccines for smallpox are effective but have risks that are no longer
      acceptable for routine use in populations at minimal risk of infection. We have
      developed a mucosal, killed-vaccinia virus (VV) vaccine based on antimicrobial
      nanoemulsion (NE) of soybean oil and detergent. Incubation of VV with 10% NE for
      at least 60 min causes the complete disruption and inactivation of VV. Simple
      mixtures of NE and VV (Western Reserve serotype) (VV/NE) applied to the nares of
      mice resulted in both systemic and mucosal anti-VV immunity, virus-neutralizing
      antibodies, and Th1-biased cellular responses. Nasal vaccination with VV/NE
      vaccine produced protection against lethal infection equal to vaccination by
      scarification, with 100% survival after challenge with 77 times the 50% lethal
      dose of live VV. However, animals protected with VV/NE immunization did after
      virus challenge have clinical symptoms more extensive than animals vaccinated by
      scarification. VV/NE-based vaccines are highly immunogenic and induce protective
      mucosal and systemic immunity without the need for an inflammatory adjuvant or
      infection with live virus.

PMID- 18057183
TI  - Evaluation of the ultrasensitive human immunodeficiency virus type 1 (HIV-1) p24
      antigen assay performed on dried blood spots for diagnosis of HIV-1 infection in
      infants.
AB  - The diagnostic accuracy of the modified p24 antigen assay performed on pediatric
      dried blood spots was evaluated. Samples analyzed within 6 weeks of collection
      yielded no false-positive results (specificity, 100%) and few false-negative
      results (sensitivity, 96.5% to 98.3%). Laboratory services with limited resources
      should assess this option for routine infant diagnosis.

PMID- 18057184
TI  - Serological evaluation of specific-antibody levels in patients treated for
      chronic Chagas' disease.
AB  - Serological tests are the main laboratory procedures used for diagnosis during
      the indeterminate and chronic stages of Chagas' disease. A serological regression
      to negativity is the main criterion used to define parasitological cure in
      treated patients. The aim of this work was to monitor the individual
      specificities of antibody levels for 3 years posttreatment in 18 adult patients.
      Conventional serological techniques (hemagglutination assays and enzyme-linked
      immunosorbent assay [ELISA]) were modified by using recombinant antigens to
      detect early markers of treatment effectiveness. For this purpose, serum samples
      were taken before and during treatment and every 6 months after treatment for at
      least 3 years. When hemagglutination assays were used, a decrease in antibody
      levels was observed in only one patient. When ELISA with serum dilutions was
      used, antibody clearance became much more apparent: in 77.7% (14/18) of the
      patients, antibody titers became negative with time. This was observed at serum
      dilutions of 1/320 and occurred between the 6th and the 30th months
      posttreatment. The immune response and the interval for a serological regression
      to negativity were different for each patient. For some of the recombinant
      antigens, only 50% (9/18) of the patients reached the serological regression to
      negativity. Recombinant antigen 13 might be a good marker of treatment
      effectiveness, since 66.6% (six of nine) of the patients presented with an early
      regression to negativity for specific antibodies to this antigen (P = 0.002).

PMID- 18057185
TI  - Impaired acid secretion in cortical collecting duct intercalated cells from H-K
      ATPase-deficient mice: role of HKalpha isoforms.
AB  - Two classes of H pumps, H-K-ATPase and H-ATPase, contribute to luminal
      acidification and HCO(3) transport in the collecting duct (CD). At least two H-K
      ATPase alpha-subunits are expressed in the CD: HKalpha(1) and HKalpha(2). Both
      exhibit K dependence but have different inhibitor sensitivities. The HKalpha(1) H
      K-ATPase is Sch-28080 sensitive, whereas the pharmacological profile of the
      HKalpha(2) H-K-ATPase is not completely understood. The present study used a
      nonpharmacological, genetic approach to determine the contribution of HKalpha(1)
      and HKalpha(2) to cortical CD (CCD) intercalated cell (IC) proton transport in
      mice fed a normal diet. Intracellular pH (pH(i)) recovery was determined in ICs
      using in vitro microperfusion of CCD after an acute intracellular acid load in
      wild-type mice and mice of the same strain lacking expression of HKalpha(1),
      HKalpha(2), or both H-K-ATPases (HKalpha(1,2)). A-type and B-type ICs were
      differentiated by luminal loading with BCECF-AM and peritubular chloride removal
      from CO(2)/HCO(3)-buffered solutions to identify the membrane locations of
      Cl/HCO(3) exchange activity. H-ATPase- and Na/H exchange-mediated H transport
      were inhibited with bafilomycin A(1) (100 nM) and EIPA (10 microM), respectively.
      Here, we report 1) initial pH(i) and buffering capacity were not significantly
      altered in the ICs of HKalpha-deficient mice, 2) either HKalpha(1) or HKalpha(2)
      deficiency resulted in slower acid extrusion, and 3) A-type ICs from HKalpha(1,2)
      deficient mice had significantly slower acid extrusion compared with A-type ICs
      from HKalpha(1)-deficient mice alone. These studies are the first
      nonpharmacological demonstration that both HKalpha(1) and HKalpha(2) contribute
      to H secretion in both A-type and B-type ICs in animals fed a normal diet.

PMID- 18057186
TI  - Renal localization and regulation of 15-hydroxyprostaglandin dehydrogenase.
AB  - Tissue prostaglandin levels are determined by both biosynthesis and catabolism.
      The current studies report the expression and localization of 15
      hydroxyprostaglandin dehydrogenase (15-PGDH), a key enzyme in prostaglandin
      catabolism in the kidneys. We also investigated potential interactions between 15
      PGDH and cyclooxygenase (COX), a key enzyme in prostaglandin biosynthesis. Both
      15-PGDH mRNA and protein levels were significantly higher in kidney cortex than
      in papilla, which is opposite to the expression pattern of COX-2. In situ
      hybridization indicated that 15-PGDH mRNA was mainly localized to the tubular
      epithelial cells in kidney cortex and outer medulla but not in the glomerulus or
      papilla. Dual immunofluorescent staining indicated that 15-PGDH was expressed in
      the proximal tubule, cortical, and outer medullary thick ascending limb and
      collecting duct but not in the macula densa or papilla. 15-PGDH levels were
      significantly lower in a macula densa cell line (MMDD1) than in a proximal tubule
      cell line. Although a high-salt diet decreased COX-2 expression in macula densa,
      it increased macula densa 15-PGDH expression in both mouse and rat kidneys. In
      MMDD1 cells, a COX-2 inhibitor increased 15-PGDH, whereas a COX-1 inhibitor had
      no effect. Furthermore, intense 15-PGDH immunofluorescent staining was found in
      both macula densa and glomerulus in COX-2 knockout mice. The intrarenal
      distribution of 15-PGDH and its interactions with COX-2 suggest that differential
      regulation of COX-2 and 15-PGDH may play an important role in determining levels
      of prostaglandins involved in regulation of salt, volume, and blood pressure
      homeostasis.

PMID- 18057187
TI  - Sevoflurane-mediated TGF-beta1 signaling in renal proximal tubule cells.
AB  - Several volatile anesthetics, including sevoflurane, protect against renal
      ischemia-reperfusion injury in vivo by reducing necrosis and inflammation.
      Furthermore, in cultured renal tubule cells, sevoflurane directly induced the
      phosphorylation of the cytoprotective kinases (ERK and Akt), upregulated 70-kDa
      heat shock protein (HSP70), and attenuated nuclear translocation of the
      proinflammatory transcription factor NF-kappaB. It has been shown that
      sevoflurane increases the release of transforming growth factor-beta1 (TGF-beta1)
      in human proximal tubule (HK-2) cells via externalization of plasma membrane
      phosphatidylserine (PS), and this increase in TGF-beta1 protected HK-2 cells
      against hydrogen peroxide-mediated necrosis. In this study, we aimed to determine
      whether the sevoflurane-mediated phosphorylation of ERK and Akt, induction of
      HSP70, and reduction in NF-kappaB activation are due to TGF-beta1 receptor
      mediated signaling after PS externalization in HK-2 cells. Exogenous TGF-beta1
      and a liposome mixture containing PS mimicked sevoflurane-mediated ERK and Akt
      phosphorylation and HSP70 induction in HK-2 cells. Sevoflurane and TGF-beta1
      caused the nuclear translocation of the SMAD3 transcription factor in HK-2 cells.
      Furthermore, a neutralizing TGF-beta1 antibody or exogenous annexin V to bind PS
      prevented sevoflurane-induced ERK and Akt phosphorylation and HSP70 induction in
      HK-2 cells. Finally, a TGF-beta1 antibody and annexin V attenuated the reduction
      in nuclear translocation of NF-kappaB by sevoflurane. Therefore, we demonstrate
      in this study that sevoflurane-mediated cytoprotective and anti-inflammatory
      effects in HK-2 cells are at least partially due to the externalization of PS and
      activation of TGF-beta1 signaling pathways.

PMID- 18057188
TI  - Predicting utility ratings for joint health States from single health States in
      prostate cancer: empirical testing of 3 alternative theories.
AB  - BACKGROUND: Cost-effectiveness analyses measure quality of life by associating
      utilities with specific health states. Utilities are often defined by single
      health states, such as incontinence or impotence in the case of prostate cancer
      treatments. Health conditions often occur simultaneously, yielding joint health
      states (e.g., impotence with incontinence). Given the combinatorial mathematics
      involved, even a small number of conditions can result in large numbers of
      potential joint states, complicating utility elicitation for all relevant states.
      Analytic predictions for joint-state utilities have been based on 3 theoretical
      models: 1) multiplicative, 2) additive, and 3) minimum models. These models'
      empirical accuracy for joint-state utility prediction has been minimally
      examined. The authors compared these 3 models for predicting joint-state
      utilities from single-state utilities in men at the time of prostate biopsies.
      METHODS: Utilities were collected using time tradeoff in 2 university-based
      prostate biopsy clinics (N = 147). Single-state utilities were elicited for
      impotence, incontinence, watchful waiting, and post-prostatectomy. Joint-state
      utilities were elicited for states combining impotence with 1) incontinence, 2)
      postprostatectomy, or 3) watchful waiting. Testing 3 prediction models of joint
      state utilities for bias and consistency, the predictions were compared against
      directly elicited joint-state utilities. RESULTS: All 3 models are biased. The
      minimum model is preferred, being the least biased and most efficient.
      CONCLUSIONS: No current model accurately predicts joint-state utility using the
      component single-state utilities. When possible, joint-state utilities should be
      elicited. If not possible, the minimum model is recommended. Research to identify
      better models is needed.

PMID- 18057189
TI  - A second-order simulation model of the cost-effectiveness of managing dyspepsia
      in the United States.
AB  - BACKGROUND: The "gold-standard'' evidence of effectiveness for a clinical
      practice guideline is the randomized controlled trial (RCT), although RCTs have a
      limited ability to explore potential management strategies for a chronic disease
      where these interact over time. Modeling can be used to fill this gap, and models
      have become increasingly complex, with both dynamic sampling and representation
      of second-order uncertainty to provide more precise estimates. However, both
      simulation modeling and probabilistic sensitivity analysis are rarely used
      together. The objective of this study was to explore uncertainty in controversial
      areas of the 2005 American Gastroenterology Association position statement on the
      management of dyspepsia. METHODS: Individual sampling model, incorporating a
      second-order probabilistic sensitivity analysis. POPULATION: US adult patients
      presenting in primary care with dyspepsia. Interventions compared: empirical acid
      suppression, test and treat for Helicobacter pylori, initial endoscopy, acid
      suppression then endoscopy, test and treat then proton pump inhibitor (PPI) then
      endoscopy. OUTCOMES: Cost-effectiveness, quality-adjusted life years, and costs
      in US dollars from a societal perspective, measured over a 5-year period. DATA
      SOURCES: mainly Cochrane meta-analyses. RESULTS: Endoscopy was dominated at all
      ages by other strategies. PPI therapy was the most cost-effective strategy in 30
      year-olds with a low prevalence of H. pylori. In 60-year-olds, H. pylori test and
      treat was the most cost-effective option. CONCLUSIONS: Acid suppression alone was
      more cost-effective than either endoscopy or H. pylori test and treat in younger
      dyspepsia patients with a low prevalence of infection.

PMID- 18057190
TI  - Measuring the care of the patient in context.

PMID- 18057191
TI  - A systematic review of cost-utility analyses in HIV/AIDS: implications for public
      policy.
AB  - OBJECTIVES: To determine whether gaps exist in published cost-utility analyses as
      measured by their coverage of topics addressed in current HIV guidelines from the
      Department of Health and Human Services (DHHS). DESIGN: A systematic review of US
      based cost-effectiveness analyses of HIV/AIDS prevention and management
      strategies, based on original, published research. METHODS: Predefined criteria
      were used to identify all analyses pertaining to prevention and management of
      HIV/AIDS; information was collected on type of strategy, patient demographics,
      study perspective, quality of the study, effectiveness measures, costs, and cost
      effectiveness ratios. RESULTS: One hundred and six studies were identified; 62
      described strategies for averting new HIV infections, and 44 dealt with managing
      persons who are HIV positive. The quality of studies was generally high, but gaps
      were found in all studies. Especially common were omissions in reporting data
      abstraction methodology and discussions of direction and magnitude of potential
      biases. Among the 22 most highly rated papers (score of 90 or higher), only 1 was
      cited in the guidelines, and 3 papers reported on interventions that were
      superseded by newer approaches. Using a USD 100,000 threshold, the guidelines
      usually endorsed interventions found to be cost-effective. Exceptions included
      recommending postexposure prophylaxis (PEP) for populations in which PEP is
      unlikely to be cost-effective and not recommending primary resistance testing in
      treatment-naive persons, although the intervention was reported to have a cost
      effectiveness ratio of less than USD 50,000. CONCLUSIONS: Despite an abundant
      literature on the cost-utility of HIV/AIDS-targeted strategies, guidelines cite
      relatively few of these papers, and gaps exist regarding assessments of some
      strategies and special populations.

PMID- 18057192
TI  - Swimming with and against the stream: does motor adaptation to lateral forces
      influence visual motion perception?

PMID- 18057193
TI  - Serotonin, the prefrontal cortex, and the antidepressant-like effect of
      cannabinoids.

PMID- 18057194
TI  - Heroin abuse is characterized by discrete mesolimbic dopamine and opioid
      abnormalities and exaggerated nuclear receptor-related 1 transcriptional decline
      with age.
AB  - Dysfunction of mesocorticolimbic dopaminergic neurons is considered a common
      feature of all drugs of abuse, yet few investigations have evaluated the dopamine
      (DA) system in nonstimulant human abusers. We examined mRNA expression levels of
      DA transporter (DAT), tyrosine hydroxylase (TH), dopamine D2 receptor, alpha
      synuclein, and nuclear receptor-related 1 (Nurr1) in discrete mesocorticolimbic
      and nigrostriatal subpopulations of heroin users and control subjects. The
      chronic use of heroin was significantly associated with decreased DAT mRNA
      expression localized to the paranigral nucleus (PN) and the mesolimbic division
      of the ventral tegmental area (VTA) with no alterations in nigrostriatal
      populations. Consistently, the density of DAT immunoreactivity was significantly
      reduced in the nucleus accumbens but not in dorsal striatum, mesolimbic and
      nigrostriatal efferent targets, respectively. Significant alteration of the mRNA
      expression of Nurr1, a transcription factor that regulates DAT expression, was
      also confined to the PN. Moreover, the results revealed an exaggerated reduction
      of Nurr1 expression with age in heroin users (r = -0.8268, p < 0.001 vs controls,
      r = -0.6204, p = 0.0746). TH and alpha-synuclein mRNA levels were, in contrast,
      elevated in the VTA PN in heroin users with no change of the D2 receptor.
      Evaluating midbrain mu- and kappa-opioid receptors, relevant for the action of
      heroin and regulation of DA neurons, revealed dysregulation of G-protein coupling
      selective to the VTA PN. Altogether the current findings provide direct
      neurobiological evidence that midbrain reward circuits have the most prominent DA
      and opioid impairments in human heroin abusers and that abnormal Nurr1
      transcription with opiate use may exacerbate limbic dysfunction with age.

PMID- 18057195
TI  - Experimental investigation of antibody-mediated clearance mechanisms of amyloid
      beta in CNS of Tg-SwDI transgenic mice.
AB  - Novel amyloid precursor protein transgenic mice, which contain the Swedish as
      well as the vasculotropic Dutch and Iowa mutations (Tg-SwDI), were used to
      investigate the mechanisms of antibody-mediated clearance of amyloid-beta (Abeta)
      from the brain. Export of the Abeta-DI peptide across the blood-brain barrier is
      severely reduced because of the vasculotropic mutations. Therefore, antibody
      mediated clearance of Abeta-DI is dependent on antibodies entering the brain. In
      this report, we immunized Tg-SwDI mice with various peptide antigens, including
      Abeta40-DI, Abeta42, and an Abeta epitope vaccine. Immunization of Tg-SwDI mice
      with substantial cortical diffuse and vascular fibrillar deposits failed to
      promote clearance of parenchymal or vascular amyloid deposits. We then immunized
      young Tg-SwDI mice before the accumulation of Abeta and saw no evidence that anti
      Abeta antibodies could diminish deposition of parenchymal or vascular amyloid
      deposits. However, injection of anti-Abeta antibodies, affinity-purified from
      immunized Tg-SwDI mice, into the hippocampus induced a rapid clearance of diffuse
      Abeta deposits but not vascular amyloid deposits. These results further support
      the "peripheral sink hypothesis" as a legitimate mechanism of antibody-mediated
      clearance of Abeta when the blood-brain barrier remains intact. Thus, approaches
      that deliver immunotherapy to the brain may be more effective at clearing Abeta
      than immunization strategies in which the majority of the antibodies are in the
      periphery.

PMID- 18057196
TI  - Counting on inhibition and rate-dependent excitation in the auditory system.
AB  - The intervals between acoustic elements are important in audition. Although
      neurons have been recorded that show interval tuning, the underlying mechanisms
      are unclear. The anuran auditory system is well suited for addressing this
      problem. One class of midbrain neurons in anurans responds selectively over a
      narrow range of pulse-repetition rates (PRRs) and only after several sound pulses
      have occurred with the "correct" timing. This "interval-counting" process can be
      reset by a single incorrect interval. Here we show, from whole-cell patch
      recordings of midbrain neurons in vivo, that these computations result from
      interplay between inhibition and rate-dependent excitation. An individual pulse
      or slowly repeated pulses elicited inhibition and subthreshold excitation.
      Excitation was markedly enhanced, however, when PRR was increased over a neuron
      specific range. Spikes were produced when the enhanced excitation overcame the
      inhibition. Interval-number thresholds were positively correlated with the
      strength of inhibition and number of intervals required to augment the
      excitation. Accordingly, interval-number thresholds decreased when inhibition was
      attenuated by loading cells with cesium fluoride. The selectivity of these
      neurons for the interpulse interval, and therefore PRR, was related to the time
      course of excitatory events and the rate dependence of enhancement; for cells
      that were tuned to longer intervals, EPSPs were broader, and enhancement occurred
      at slower PRRs. The frequency tuning of the inhibition generally spanned that of
      the excitation, consistent with its role in temporal computation. These findings
      provide the first mechanistic understanding of interval selectivity and counting
      in the nervous system.

PMID- 18057197
TI  - Catechol-O-methyltransferase Val158Met modulation of prefrontal-parietal-striatal
      brain systems during arithmetic and temporal transformations in working memory.
AB  - Working memory (WM) is critically mediated by dopaminergic tuning of signal-to
      noise in cortical neural assemblies. However, little is known about the
      distributed neuronal networks impacted by dopaminergic modulation in the
      component processes of WM. Here, we used the genotype of the Val158Met
      polymorphism in catechol-O-methyltransferase (COMT) as an index of relative
      cortical dopamine bioavailability and tuning efficiency, to examine the spatial
      and subprocess specificity by which dopaminergic modulation occurs within the
      prefrontal-parietal-striatal network during WM, thus empirically showing that
      dopamine plays key roles in updating and stabilizing new information at the
      neural systems level. In an event-related fMRI task dissociating component
      numerical WM subprocesses, baseline numerical size comparison engaged
      ventrolateral prefrontal cortical activation that correlated with COMT Val-allele
      load (COMT Val>Met), while performing arithmetic transformations further engaged
      this genotype effect in dorsolateral prefrontal cortex (DLPFC), as well as in
      parietal and striatal regions. Critically, additional temporal integration of
      information in WM disproportionately engaged greater COMT Val>Met effects only at
      DLPFC. COMT Val>Met effects were also observed in DLPFC during encoding of new
      information into WM, but not at its subsequent retrieval. Thus, temporal updating
      operations, but less so the retrieval of already encoded representations, engaged
      relatively specific dopaminergic tuning at the DLPFC. Manipulating and rapidly
      updating representations were sensitive to dopaminergic modulation of neural
      signaling in a larger prefrontal-parietal-striatal network. These findings add to
      the integration of dopaminergic signaling in basic cortical assemblies with their
      roles in specific human brain networks during the orchestration of information
      processing in WM.

PMID- 18057198
TI  - Tyramine and octopamine independently inhibit serotonin-stimulated aversive
      behaviors in Caenorhabditis elegans through two novel amine receptors.
AB  - Biogenic amines modulate key behaviors in both vertebrates and invertebrates. In
      Caenorhabditis elegans, tyramine (TA) and octopamine (OA) inhibit aversive
      responses to 100%, but not dilute (30%) octanol. TA and OA also abolish food- and
      serotonin-dependent increases in responses to dilute octanol in wild-type but not
      tyra-3(ok325) and f14d12.6(ok371) null animals, respectively, suggesting that TA
      and OA modulated responses to dilute octanol are mediated by separate, previously
      uncharacterized, G-protein-coupled receptors. TA and OA are high-affinity ligands
      for TYRA-3 and F14D12.6, respectively, based on their pharmacological
      characterization after heterologous expression. f14d12.6::gfp is expressed in the
      ASHs, the neurons responsible for sensitivity to dilute octanol, and the sra-6
      dependent expression of F14D12.6 in the ASHs is sufficient to rescue OA
      sensitivity in f14d12.6(ok371) null animals. In contrast, tyra-3::gfp appears not
      to be expressed in the ASHs, but instead in other neurons, including the
      dopaminergic CEP/ADEs. However, although dopamine (DA) also inhibits 5-HT
      dependent responses to dilute octanol, TA still inhibits in dop-2; dop-1; dop-3
      animals that do not respond to DA and cat-2(tm346) and Pdat-1::ICE animals that
      lack significant dopaminergic signaling, suggesting that DA is not an
      intermediate in TA inhibition. Finally, responses to TA and OA selectively
      desensitize after preexposure to the amines. Our data suggest that although
      tyraminergic and octopaminergic signaling yield identical phenotypes in these
      olfactory assays, they act independently through distinct receptors to modulate
      the ASH-mediated locomotory circuit and that C. elegans is a useful model to
      study the aminergic modulation of sensory-mediated locomotory behaviors.

PMID- 18057199
TI  - Impairment of retention but not acquisition of a visuomotor skill through time
      dependent disruption of primary motor cortex.
AB  - Learning a visuomotor skill involves a distributed network which includes the
      primary motor cortex (M1). Despite multiple lines of evidence supporting the role
      of M1 in motor learning and memory, it is unclear whether M1 plays distinct roles
      in different aspects of learning such as acquisition and retention. Here, we
      investigated the nature and chronometry of that processing through a temporally
      specific disruption of M1 activity using single-pulse transcranial magnetic
      stimulation (TMS). We applied single-pulse TMS to M1 or dorsal premotor cortex
      (PMd) during adaptation of rapid arm movements (approximately 150 ms duration) to
      a visuomotor rotation. When M1 was stimulated either immediately after the end of
      each trial or with a 700 ms delay, subjects exhibited normal adaptation. However,
      whereas the memory of the subjects who received delayed-TMS showed normal rates
      of forgetting during deadaptation, the memory of those who received immediate TMS
      was more fragile: in the deadaptation period, they showed a faster rate of
      forgetting. Stimulation of PMd with adjusted (reduced) intensity to rule out the
      possibility of coactivation of this structure caused by the current spread from
      M1 stimulation did not affect adaptation or retention. The data suggest that,
      during the short time window after detection of movement errors, neural
      processing in M1 plays a crucial role in formation of motor memories. This
      processing in M1 may represent a slow component of motor memory which plays a
      significant role in retention.

PMID- 18057200
TI  - Differential gating and recruitment of P/Q-, N-, and R-type Ca2+ channels in
      hippocampal mossy fiber boutons.
AB  - Voltage-gated Ca2+ channels in presynaptic terminals initiate the Ca2+ inflow
      necessary for transmitter release. At a variety of synapses, multiple Ca2+
      channel subtypes are involved in synaptic transmission and plasticity. However,
      it is unknown whether presynaptic Ca2+ channels differ in gating properties and
      whether they are differentially activated by action potentials or subthreshold
      voltage signals. We examined Ca2+ channels in hippocampal mossy fiber boutons
      (MFBs) by presynaptic recording, using the selective blockers omega-agatoxin IVa,
      omega-conotoxin GVIa, and SNX-482 to separate P/Q-, N-, and R-type components.
      Nonstationary fluctuation analysis combined with blocker application revealed a
      single MFB contained on average approximately 2000 channels, with 66% P/Q-, 26% N
      , and 8% R-type channels. Whereas both P/Q-type and N-type Ca2+ channels showed
      high activation threshold and rapid activation and deactivation, R-type Ca2+
      channels had a lower activation threshold and slower gating kinetics. To
      determine the efficacy of activation of different Ca2+ channel subtypes by
      physiologically relevant voltage waveforms, a six-state gating model reproducing
      the experimental observations was developed. Action potentials activated P/Q-type
      Ca2+ channels with high efficacy, whereas N- and R-type channels were activated
      less efficiently. Action potential broadening selectively recruited N- and R-type
      channels, leading to an equalization of the efficacy of channel activation. In
      contrast, subthreshold presynaptic events activated R-type channels more
      efficiently than P/Q- or N-type channels. In conclusion, single MFBs coexpress
      multiple types of Ca2+ channels, which are activated differentially by
      subthreshold and suprathreshold presynaptic voltage signals.

PMID- 18057201
TI  - A selective role for neuronal activity regulated pentraxin in the processing of
      sensory-specific incentive value.
AB  - Neuronal activity regulated pentraxin (Narp) is a secreted neuronal product which
      clusters AMPA receptors and regulates excitatory synaptogenesis. Although Narp is
      selectively enriched in brain, its role in behavior is not known. As Narp is
      expressed prominently in limbic regions, we examined whether Narp deletion
      affects performance on tasks used to assess motivational consequences of food
      rewarded learning. Narp knock-out (KO) mice were unimpaired in learning simple
      pavlovian discriminations, instrumental lever pressing, and in acquisition of at
      least two aspects of pavlovian incentive learning, conditioned reinforcement and
      pavlovian-instrumental transfer. In contrast, Narp deletion resulted in a
      substantial deficit in the ability to use specific outcome expectancies to
      modulate instrumental performance in a devaluation task. In this task, mice were
      trained to respond on two levers for two different rewards. After training, mice
      were prefed with one of the two rewards, devaluing it. Responding on both levers
      was then assessed in extinction. Whereas control mice showed a significant
      preference in responding on the lever associated with the nondevalued reward,
      Narp KO mice responded equally on both levers, failing to suppress responding on
      the lever associated with the devalued reward. Both groups consumed more of the
      nondevalued reward in a subsequent choice test, indicating Narp KO mice could
      distinguish between the rewards themselves. These data suggest Narp has a
      selective role in processing sensory-specific information necessary for
      appropriate devaluation performance, but not in general motivational effects of
      reward-predictive cues on performance.

PMID- 18057202
TI  - Activation of hippocampal nuclear factor-kappa B by retrieval is required for
      memory reconsolidation.
AB  - Initially, memory is labile and requires consolidation to become stable. However,
      several studies support that consolidated memories can undergo a new period of
      lability after retrieval. The mechanistic differences of this process, termed
      reconsolidation, with the consolidation process are under debate, including the
      participation of hippocampus. Up to this point, few reports describe molecular
      changes and, in particular, transcription factor (TF) involvement in memory
      restabilization. Increasing evidence supports the participation of the TF nuclear
      factor-kappaB (NF-kappaB) in memory consolidation. Here, we demonstrate that the
      inhibition of NF-kappaB after memory reactivation impairs retention of a
      hippocampal-dependent inhibitory avoidance task in mice. We used two independent
      disruptive strategies to reach this conclusion. First, we administered
      intracerebroventricular or intrahippocampal sulfasalazine, an inhibitor of IKK
      (IkappaB kinase), the kinase that activates NF-kappaB. Second, we infused
      intracerebroventricular or intrahippocampal kappaB decoy, a direct inhibitor of
      NF-kappaB consisting of a double-stranded DNA oligonucleotide that contains the
      kappaB consensus sequence. When injected immediately after memory retrieval,
      sulfasalazine or kappaB decoy (Decoy) impaired long-term retention. In contrast,
      a one base mutated kappaB decoy (mDecoy) had no effect. Furthermore, we also
      found NF-kappaB activation in the hippocampus, with a peak 15 min after memory
      retrieval. This activation was earlier than that found during consolidation.
      Together, these results indicate that NF-kappaB is an important transcriptional
      regulator in memory consolidation and reconsolidation in hippocampus, although
      the temporal kinetics of activation differs between the two processes.

PMID- 18057203
TI  - NR2B signaling regulates the development of synaptic AMPA receptor current.
AB  - The postnatal maturation of glutamatergic synapses involves a change in
      composition and functional contribution of postsynaptic receptors. Developing
      cortical synapses are dominated by NMDA receptors (NMDARs) containing NR2B
      subunits and are characterized by a low ratio of AMPA/NMDA receptor-mediated
      current. Synapse maturation is marked by the incorporation of NR2A-containing
      NMDA receptors and an increase in the AMPA/NMDA current ratio. We show here that
      NMDARs containing the NR2B subunit regulate glutamatergic transmission at
      developing synapses by negatively influencing the synaptic incorporation of AMPA
      receptors (AMPARs). Genetic removal of NR2B leads to increased surface expression
      and synaptic localization of AMPA receptor subunits and a corresponding increase
      in AMPAR-mediated synaptic current. Enrichment of synaptic AMPARs, in the absence
      of NR2B signaling, is associated with increased levels of transmembrane AMPAR
      regulatory protein (TARP) expression and is blocked by expression of a dominant
      negative TARP construct (gamma-2deltaC). These observations suggest that NR2B
      signaling limits AMPA receptor incorporation at developing synapses by negatively
      regulating TARP expression and provide a mechanism to explain the maintenance of
      low AMPA/NMDA ratio at immature glutamatergic synapses.

PMID- 18057204
TI  - Modulation of CA3 afferent inputs by novelty and theta rhythm.
AB  - Models of hippocampal function suggest that the modulation of CA3 afferent input
      during theta rhythm allows for a rapid alternation between encoding and retrieval
      states, with each phase enhancing either extrinsic or intrinsic CA3 afferents,
      favoring either encoding or retrieval, respectively. Here, we show that during
      the initial exploration of a novel environment by rats, intrinsic CA3-CA3
      synaptic inputs are attenuated on CA3 theta peaks, favoring extrinsic CA3 inputs,
      whereas extrinsic perforant path-CA3 synaptic inputs are attenuated on CA3 theta
      troughs, favoring intrinsic CA3 inputs. This modulation is absent when animals
      are re-exposed to the same environment 2 or 48 h later and thus habituates with
      familiarity, suggesting a process involved in learning. Modulation of CA3
      synaptic inputs during novelty was blocked by atropine at a dose that blocks type
      2 theta rhythm. Re-exposure to the same novel environment 48 h later in the
      absence of atropine did not result in habituation, but instead modulated CA3
      synaptic responses as though the environment were novel and explored for the
      first time. The NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl
      1-phosphonic acid (CPP), administered in a dose that blocks long-term
      potentiation induction, did not alter CA3 synaptic modulation during initial
      exploration. However, like atropine, CPP blocked the habituation of synaptic
      modulation normally observed with re-exposure, as though the environment were
      novel and explored for the first time. Thus, as predicted theoretically,
      recurrent and cortical CA3 afferents are differentially modulated during phases
      of theta rhythm. This modulation is atropine sensitive and habituates in an NMDA
      receptor-dependent manner, suggesting an NMDA receptor-dependent process that, in
      conjunction with theta rhythm, contributes to encoding of novel information in
      the hippocampus.

PMID- 18057205
TI  - Light-evoked calcium responses of isolated melanopsin-expressing retinal ganglion
      cells.
AB  - A small number (<2%) of mammalian retinal ganglion cells express the photopigment
      melanopsin and are intrinsically photosensitive (ipRGCs). Light depolarizes
      ipRGCs and increases intracellular calcium levels ([Ca2+]i) but the signaling
      cascades underlying these responses have yet to be elucidated. To facilitate
      physiological studies on these rare photoreceptors, highly enriched ipRGC
      cultures from neonatal rats were generated using anti-melanopsin-mediated plate
      adhesion (immunopanning). This novel approach enabled experiments on isolated
      ipRGCs, eliminating the potential confounding influence of rod/cone-driven input.
      Light induced a rise in [Ca2+]i (monitored using fura-2 imaging) in the
      immunopanned ipRGCs and the source of this Ca2+ signal was investigated. The Ca2+
      responses were inhibited by 2-aminoethoxydiphenyl borate, SKF-96365 (1-2-(4
      methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole), flufenamic
      acid, lanthanum, and gadolinium, consistent with the involvement of canonical
      transient receptor potential (TRP) channels in ipRGC phototransduction. However,
      the contribution of direct Ca2+ flux through a putative TRP channel to ipRGC
      [Ca2+]i was relatively small, as most (approximately 90%) of the light-induced
      Ca2+ responses could be blocked by preventing action potential firing with
      tetrodotoxin. The L-type voltage-gated Ca2+ channel (VGCC) blockers verapamil and
      (+)-cis-diltiazem significantly reduced the light-evoked Ca2+ responses, while
      the internal Ca2+ stores depleting agent thapsigargin had negligible effect.
      These results indicate that Ca2+ influx through VGCCs, activated after action
      potential firing, was the primary source for light-evoked elevations in ipRGC
      [Ca2+]i. Furthermore, concurrent Ca2+ imaging and cell-attached
      electrophysiological recordings demonstrated that the Ca2+ responses were highly
      correlated to spike frequency, thereby establishing a direct link between action
      potential firing and somatic [Ca2+]i in light-stimulated ipRGCs.

PMID- 18057206
TI  - EphB receptors regulate stem/progenitor cell proliferation, migration, and
      polarity during hippocampal neurogenesis.
AB  - The adult brain maintains two regions of neurogenesis from which new neurons are
      born, migrate to their appropriate location, and become incorporated into the
      circuitry of the CNS. One of these, the subgranular zone of the hippocampal
      dentate gyrus, is of primary interest because of the role of this region in
      learning and memory. We show that mice lacking EphB1, and more profoundly EphB1
      and EphB2, have significantly fewer neural progenitors in the hippocampus.
      Furthermore, other aspects of neurogenesis, such as polarity, cell positioning,
      and proliferation are disrupted in animals lacking the EphB1 receptor or its
      cognate ephrin-B3 ligand. Our data strongly suggest that EphB1 and ephrin-B3
      cooperatively regulate the proliferation and migration of neural progenitors in
      the hippocampus and should be added to a short list of candidate target molecules
      for modulating the production and integration of new neurons as a treatment for
      neurodegenerative diseases or brain injury.

PMID- 18057207
TI  - Prenatal and adolescent exposure to tobacco smoke modulates the development of
      white matter microstructure.
AB  - Prenatal exposure to maternal smoking has been linked to cognitive and auditory
      processing deficits in offspring. Preclinical studies have demonstrated that
      exposure to nicotine disrupts neurodevelopment during gestation and adolescence,
      possibly by disrupting the trophic effects of acetylcholine. Given recent
      clinical and preclinical work suggesting that neurocircuits that support auditory
      processing may be particularly vulnerable to developmental disruption by
      nicotine, we examined white matter microstructure in 67 adolescent smokers and
      nonsmokers with and without prenatal exposure to maternal smoking. The groups did
      not differ in age, educational attainment, IQ, years of parent education, or
      symptoms of inattention. Diffusion tensor anisotropy and anatomical magnetic
      resonance images were acquired, and auditory attention was assessed, in all
      subjects. Both prenatal exposure and adolescent exposure to tobacco smoke was
      associated with increased fractional anisotropy (FA) in anterior cortical white
      matter. Adolescent smoking was also associated with increased FA of regions of
      the internal capsule that contain auditory thalamocortical and corticofugal
      fibers. FA of the posterior limb of the left internal capsule was positively
      correlated with reaction time during performance of an auditory attention task in
      smokers but not in nonsmokers. Development of anterior cortical and internal
      capsule fibers may be particularly vulnerable to disruption in cholinergic
      signaling induced by nicotine in tobacco smoke. Nicotine-induced disruption of
      the development of auditory corticofugal fibers may interfere with the ability of
      these fibers to modulate ascending auditory signals, leading to greater noise and
      reduced efficiency of neurocircuitry that supports auditory processing.

PMID- 18057208
TI  - Synaptic plasticity and calcium signaling in Purkinje cells of the central
      cerebellar lobes of mormyrid fish.
AB  - Climbing fiber (CF)-evoked calcium transients play a key role in plasticity at
      parallel fiber (PF) to Purkinje cell synapses in the mammalian cerebellum.
      Whereas PF activation alone causes long-term potentiation (LTP), coactivation of
      the heterosynaptic CF input, which evokes large dendritic calcium transients,
      induces long-term depression (LTD). This unique type of heterosynaptic
      interaction is a hallmark feature of synaptic plasticity in mammalian Purkinje
      cells. Purkinje cells in the cerebellum of mormyrid electric fish are
      characterized by a different architecture of their dendritic trees and by a more
      pronounced separation of CF and PF synaptic contact sites. We therefore examined
      the conditions for bidirectional plasticity at PF synapses onto Purkinje cells in
      the mormyrid cerebellum in vitro. PF stimulation at elevated frequencies induces
      LTP, whereas LTD results from PF stimulation at enhanced intensities and depends
      on dendritic calcium influx and metabotropic glutamate receptor type 1
      activation. LTD can also be observed after pairing of low intensity PF
      stimulation with CF stimulation. Using a combination of whole-cell patch-clamp
      recordings and fluorometric calcium imaging, we characterized calcium transients
      in Purkinje cell dendrites. CF activation elicits calcium transients not only
      within the CF input territory (smooth proximal dendrites) but also within the PF
      input territory (spiny palisade dendrites). Paired PF and CF activation elicits
      larger calcium transients than stimulation of either input alone. A major source
      for dendritic calcium signaling is provided by P/Q-type calcium channels. Our
      data show that despite the spatial separation between the two inputs CF activity
      facilitates LTD induction at PF synapses.

PMID- 18057209
TI  - The source of afterdischarge activity in neocortical tonic-clonic epilepsy.
AB  - Tonic-clonic seizures represent a common pattern of epileptic discharges, yet the
      relationship between the various phases of the seizure remains obscure. Here we
      contrast propagation of the ictal wavefront with the propagation of individual
      discharges in the clonic phase of the event. In an in vitro model of tonic-clonic
      epilepsy, the afterdischarges (clonic phase) propagate with relative uniform
      speed and are independent of the speed of the ictal wavefront (tonic phase). For
      slowly propagating ictal wavefronts, the source of the afterdischarges, relative
      to a given recording electrode, switched as the wavefront passed by, indicating
      that afterdischarges are seeded from wavefront itself. In tissue that has
      experienced repeated ictal events, the wavefront generalizes rapidly, and the
      afterdischarges in this case show a different "flip-flop" pattern, with frequent
      switches in their direction of propagation. This same flip-flop pattern is also
      seen in subdural EEG recordings in patients suffering intractable focal seizures
      caused by cortical dysplasias. Thus, in both slowly and rapidly generalizing
      ictal events, there is not a single source of afterdischarge activity: rather,
      the source is continuously changing. Our data suggest a complex view of seizures
      in which the ictal event and its constituent discharges originate from distinct
      locations.

PMID- 18057210
TI  - Lack of synapsin I reduces the readily releasable pool of synaptic vesicles at
      central inhibitory synapses.
AB  - Synapsins (Syns) are synaptic vesicle (SV) phosphoproteins that play a role in
      neurotransmitter release and synaptic plasticity by acting at multiple steps of
      exocytosis. Mutation of SYN genes results in an epileptic phenotype in mouse and
      man suggesting a role of Syns in the control of network excitability. We have
      studied the effects of the genetic ablation of the SYN1 gene on inhibitory
      synaptic transmission in primary hippocampal neurons. Inhibitory neurons lacking
      SynI showed reduced amplitude of IPSCs evoked by isolated action potentials. The
      impairment in inhibitory transmission was caused by a decrease in the size of the
      SV readily releasable pool, rather than by changes in release probability or
      quantal size. The reduction of the readily releasable pool was caused by a
      decrease in the number of SVs released by single synaptic boutons in response to
      the action potential, in the absence of variations in the number of synaptic
      contacts between couples of monosynaptically connected neurons. The deletion of
      SYN1 did not affect paired-pulse depression or post-tetanic potentiation, but was
      associated with a moderate increase of synaptic depression evoked by trains of
      action potentials, which became apparent at high stimulation frequencies and was
      accompanied by a slow down of recovery from depression. The decreased size of the
      SV readily releasable pool, coupled with a decreased SV recycling rate and
      refilling by the SV reserve pool, may contribute to the epileptic phenotype of
      SynI knock-out mice.

PMID- 18057211
TI  - How pleasant and unpleasant stimuli combine in different brain regions: odor
      mixtures.
AB  - Many affective stimuli are hedonically complex mixtures containing both pleasant
      and unpleasant components. To investigate whether the brain represents the
      overall affective value of such complex stimuli, or the affective value of the
      different components simultaneously, we used functional magnetic resonance
      imaging to measure brain activations to a pleasant odor (jasmine), an unpleasant
      odor (indole), and a mixture of the two that was pleasant. In brain regions that
      represented the pleasantness of the odors such as the medial orbitofrontal cortex
      (as shown by activations that correlated with the pleasantness ratings), the
      mixture produced activations of similar magnitude to the pleasant jasmine, but
      very different from the unpleasant indole. These regions thus emphasize the
      pleasant aspects of the mixture. In contrast, in regions representing the
      unpleasantness of odors such as the dorsal anterior cingulate and
      midorbitofrontal cortex the mixture produced activations that were relatively
      further from the pleasant component jasmine and closer to the indole. These
      regions thus emphasize the unpleasant aspects of the mixture. Thus mixtures that
      are found pleasant can have components that are separately pleasant and
      unpleasant, and the brain can separately and simultaneously represent the
      positive and negative hedonic value of a complex affective stimulus that contains
      both pleasant and unpleasant olfactory components. This type of representation
      may be important for affective decision making in the brain in that separate
      representations of different affective components of the same sensory stimulus
      may provide the inputs for making a decision about whether to choose the stimulus
      or not.

PMID- 18057212
TI  - Electrical stimulation of the midbrain for hearing restoration: insight into the
      functional organization of the human central auditory system.
AB  - The cochlear implant can restore speech perception in patients with sensorineural
      hearing loss. However, it is ineffective for those without an implantable cochlea
      or a functional auditory nerve. These patients can be implanted with the auditory
      brainstem implant (ABI), which stimulates the surface of the cochlear nucleus.
      Unfortunately, the ABI has achieved limited success in its main patient group
      [i.e., those with neurofibromatosis type 2 (NF2)] and requires a difficult
      surgical procedure. These limitations have motivated us to develop a new hearing
      prosthesis that stimulates the midbrain with a penetrating electrode array. We
      recently implanted three patients with the auditory midbrain implant (AMI), and
      it has proven to be safe with minimal movement over time. The AMI provides
      loudness, pitch, temporal, and directional cues, features that have shown to be
      important for speech perception and more complex sound processing. Thus far, all
      three patients obtain enhancements in lip reading capabilities and environmental
      awareness and some improvements in speech perception comparable with that of NF2
      ABI patients. Considering that our midbrain target is more surgically exposable
      than the cochlear nucleus, this argues for the use of the AMI as an alternative
      to the ABI. Fortunately, we were able to stimulate different midbrain regions in
      our patients and investigate the functional organization of the human central
      auditory system. These findings provide some insight into how we may need to
      stimulate the midbrain to improve hearing performance with the AMI.

PMID- 18057213
TI  - Nav1.6 sodium channels are critical to pacemaking and fast spiking in globus
      pallidus neurons.
AB  - Neurons in the external segment of the globus pallidus (GPe) are autonomous
      pacemakers that are capable of sustained fast spiking. The cellular and molecular
      determinants of pacemaking and fast spiking in GPe neurons are not fully
      understood, but voltage-dependent Na+ channels must play an important role.
      Electrophysiological studies of these neurons revealed that macroscopic
      activation and inactivation kinetics of their Na+ channels were similar to those
      found in neurons lacking either autonomous activity or the capacity for fast
      spiking. What was distinctive about GPe Na+ channels was a prominent resurgent
      gating mode. This mode was significantly reduced in GPe neurons lacking
      functional Nav1.6 channels. In these Nav1.6 null neurons, pacemaking and the
      capacity for fast spiking were impaired, as was the ability to follow stimulation
      frequencies used to treat Parkinson's disease (PD). Simulations incorporating Na+
      channel models with and without prominent resurgent gating suggested that
      resurgence was critical to fast spiking but not to pacemaking, which appeared to
      be dependent on the positioning of Na+ channels in spike-initiating regions of
      the cell. These studies not only shed new light on the mechanisms underlying
      spiking in GPe neurons but also suggest that electrical stimulation therapies in
      PD are unlikely to functionally inactivate neurons possessing Nav1.6 Na+ channels
      with prominent resurgent gating.

PMID- 18057214
TI  - The medial prefrontal cortex is involved in spatial memory retrieval under
      partial-cue conditions.
AB  - Brain circuits involved in pattern completion, or retrieval of memory from
      fragmented cues, were investigated. Using different versions of the Morris water
      maze, we explored the roles of the CA3 subregion of the hippocampus and the
      medial prefrontal cortex (mPFC) in spatial memory retrieval under various
      conditions. In a hidden platform task, both CA3 and mPFC lesions disrupted memory
      retrieval under partial-cue, but not under full-cue, conditions. For a delayed
      matching-to-place task, CA3 lesions produced a deficit in both forming and
      recalling spatial working memory regardless of extramaze cue conditions. In
      contrast, damage to mPFC impaired memory retrieval only when a fraction of cues
      was available. To corroborate the lesion study, we examined the expression of the
      immediate early gene c-fos in mPFC and the hippocampus. After training of spatial
      reference memory in full-cue conditions for 6 d, the same training procedure in
      the absence of all cues except one increased the number of Fos-immunoreactive
      cells in mPFC and CA3. Furthermore, mPFC inactivation with muscimol, a GABA
      agonist, blocked memory retrieval in the degraded-cue environment. However, mPFC
      lesioned animals initially trained in a single-cue environment had no difficulty
      in retrieving spatial memory when the number of cues was increased, demonstrating
      that contextual change per se did not impair the behavioral performance of the
      mPFC-lesioned animals. Together, these findings strongly suggest that pattern
      completion requires interactions between mPFC and the hippocampus, in which mPFC
      plays significant roles in retrieving spatial information maintained in the
      hippocampus for efficient navigation.

PMID- 18057215
TI  - Effect of pioglitazone on cardiovascular outcome in diabetes and chronic kidney
      disease.
AB  - Patients with diabetes and chronic kidney disease (CKD) are at particularly high
      risk for cardiovascular disease (CVD). This post hoc analysis from the
      PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive)
      investigated the relationship between CKD and incident CVD in a population of
      patients with diabetes and documented macrovascular disease, as well as the
      effects of pioglitazone treatment on recurrent CVD. CKD, defined as an estimated
      GFR <60 ml/min per 1.73m(2), was present in 597 (11.6%) of 5154 patients. More
      patients with CKD reached the primary composite end point (all-cause mortality,
      myocardial infarction (MI), stroke, acute coronary syndrome, coronary/carotid
      arterial intervention, leg revascularization, or amputation above the ankle) than
      patients without CKD (27.5 versus 19.6%; P < 0.0001). Patients with CKD were also
      more likely to reach a secondary composite end point (all-cause mortality, MI,
      and stroke). Patients who had CKD and were treated with pioglitazone were less
      likely to reach the secondary end point (hazard ratio 0.66; 95% confidence
      interval 0.45 to 0.98), but this association was not observed among those with
      better renal function. In addition, there was a greater decline in estimated GFR
      with pioglitazone (between-group difference 0.8 ml/min per 1.73 m(2)/yr) than
      with placebo. In conclusion, CKD is an independent risk factor for cardiovascular
      events and death among patients with diabetes and preexisting macrovascular
      disease. Patients who had CKD and were treated with pioglitazone were less likely
      to reach a composite end point of all-cause death, MI, and stroke, independent of
      the severity of renal impairment.

PMID- 18057216
TI  - Low birth weight increases risk for end-stage renal disease.
AB  - Case-control studies have shown an association between low birth weight and risk
      for renal failure. The Medical Birth Registry of Norway, which comprises data on
      all births in Norway since 1967, and the Norwegian Renal Registry, which
      comprises data on all patients who have developed ESRD in Norway since 1980, were
      used to examine whether birth-related variables were associated with risk for
      ESRD. Of the 2,183,317 children born between 1967 and 2004, 526 were found in the
      ESRD registry. Compared with birth weight in the 10th to 90th percentiles, births
      <10th percentile had a relative risk (RR) for ESRD of 1.7 (95% confidence
      interval 1.4 to 2.2; P < 0.001). Births with a weight for gestational age <10th
      percentile had an RR of 1.5 (95% confidence interval 1.2 to 1.9; P = 0.002).
      These associations were virtually identical after adjustment for birth-related
      confounders such as congenital malformations, multiple delivery, maternal age at
      birth, and maternal preeclampsia. Low birth weight was more strongly associated
      with development of ESRD during the first 14 years of life than after age 15. Low
      birth weight and low birth weight for gestational age were similarly associated
      with multiple causes of ESRD. In conclusion, in this cohort study with a maximum
      follow-up of 38 years, low birth weight and intrauterine growth restriction were
      associated with increased risk for ESRD.

PMID- 18057217
TI  - Overexpression of angiotensinogen increases tubular apoptosis in diabetes.
AB  - The intrarenal renin-angiotensin system (RAS) plays an important role in the
      progression of diabetic nephropathy. We have previously reported that mice
      overexpressing angiotensinogen in renal proximal tubular cells (RPTC) develop
      hypertension, albuminuria, and renal injury. Here, we investigated whether
      activation of the intrarenal RAS contributes to apoptosis of RPTC in diabetes.
      Induction of diabetes with streptozotocin in these transgenic mice led to
      significant increases in BP, albuminuria, RPTC apoptosis, and proapoptotic gene
      expression compared with diabetic nontransgenic littermates. Insulin and/or RAS
      blockers markedly attenuated these changes. Hydralazine prevented hypertension
      but not albuminuria, RPTC apoptosis, or proapoptotic gene expression. In vitro,
      high-glucose medium significantly increased apoptosis and caspase-3 activity in
      rat immortalized RPTC overexpressing angiotensinogen compared with control cells,
      and these changes were prevented by insulin and/or RAS blockers. In conclusion,
      intrarenal RAS activation and high glucose may act in concert to increase tubular
      apoptosis in diabetes, independent of systemic hypertension.

PMID- 18057218
TI  - Molecular mechanisms of antidiuretic effect of oxytocin.
AB  - Oxytocin is known to have an antidiuretic effect, but the mechanisms underlying
      this effect are not completely understood. We infused oxytocin by osmotic
      minipump into vasopressin-deficient Brattleboro rats for five days and observed
      marked antidiuresis, increased urine osmolality, and increased solute-free water
      reabsorption. Administration of oxytocin also significantly increased the protein
      levels of aquaporin-2 (AQP2), phosphorylated AQP2 (p-AQP2), and AQP3 in the inner
      medulla and in the outer medulla plus cortex. Immunohistochemistry demonstrated
      increased AQP2 and p-AQP2 expression and trafficking to the apical plasma
      membrane of principal cells in the collecting duct, and increased AQP3 expression
      in the basolateral membrane. These oxytocin-induced effects were blocked by
      treatment with the vasopressin V2 receptor antagonist SR121463B, but not by
      treatment with the oxytocin receptor antagonist GW796679X. We conclude that
      vasopressin V2 receptors mediate the antidiuretic effects of oxytocin, including
      increased expression and apical trafficking of AQP2, p-AQP2, and increased AQP3
      protein expression.

PMID- 18057221
TI  - Research funding at colleges of osteopathic medicine: 15 years of growth.
AB  - CONTEXT: Colleges of osteopathic medicine (COMs) trying to stimulate research and
      develop research infrastructures must overcome the challenge of obtaining
      adequate funding to support growing research interests. The authors examine
      changes in research funding at COMs during the past 15 years. OBJECTIVES: To
      track 1999-2004 data on COM research funding, COM faculty size, educational
      backgrounds of principal investigators receiving funding, and funding
      institutions. To compare these data with published results from 1989 to 1999.
      METHODS: Data on number of grants, funding amounts by extramural source, percent
      of total dollars by extramural source, percent of total dollars by COM, and total
      amount of extramural funding were obtained from the American Association of
      Colleges of Osteopathic Medicine databases. Data on the Osteopathic Research
      Center (ORC) were obtained from the ORC's databases. RESULTS: Research, both in
      terms of number of grants and funding amounts within the osteopathic medical
      profession, increased substantially from 1999 to 2004. The largest single source
      of funding remained the National Institutes of Health. The number of COMs whose
      research funding exceeded $1 million annually more than doubled, increasing from
      5 in 1999 to 12 in 2004. The osteopathic medical profession's decision to direct
      research dollars into a national research center devoted to research specific to
      osteopathic manipulative medicine resulted in an almost eightfold return on
      initial investment in 4 years. CONCLUSIONS: The amount of research productivity
      at a COM may be aligned with the size of the COM's full-time faculty, suggesting
      that once "critical mass" for teaching, service, and administration are achieved,
      a productive research program can be realized. Expanding the evidence base for
      those aspects of medicine unique to the osteopathic medical profession is
      dependent on the future growth of research.

PMID- 18057219
TI  - Neighborhood poverty and racial differences in ESRD incidence.
AB  - Poverty is associated with increased risk of ESRD, but its contribution to
      observed racial differences in disease incidence is not well-defined. To explore
      the contribution of neighborhood poverty to racial disparity in ESRD incidence,
      we analyzed a combination of US Census and ESRD Network 6 data comprising 34,767
      patients that initiated dialysis in Georgia, North Carolina, or South Carolina
      between January 1998 and December 2002. Census tracts were used as the geographic
      units of analysis, and the proportion of the census tract population living below
      the poverty level was our measure of neighborhood poverty. Incident ESRD rates
      were modeled using two-level Poisson regression, where race, age and gender were
      individual covariates (level 1), and census tract poverty was a neighborhood
      covariate (level 2). Neighborhood poverty was strongly associated with higher
      ESRD incidence for both blacks and whites. Increasing poverty was associated with
      a greater disparity in ESRD rates between blacks and whites, with the former at
      greater risk. This raises the possibility that blacks may suffer more from lower
      socioeconomic conditions than whites. The disparity persisted across all poverty
      levels. The reasons for increasingly higher ESRD incidence among US blacks as
      neighborhood poverty increases remain to be explained.

PMID- 18057222
TI  - Intercountry adoptions: medical aspects for the whole family.
AB  - In the United States, the number of intercountry adoptions has steadily increased
      in the past 15 years. Healthcare providers should understand the medical aspects
      of such adoptions in order to better advise families and aid them in making an
      informed decision when adopting a foreign-born child. Pretravel consultation is
      addressed, including immunizations, safety issues, and how to create a
      personalized prophylactic medical travel kit. Review of pictures, videos, and the
      medical history of the potential adoptive child is also discussed, as is air
      travel with children. Postemigration medical examinations-including developmental
      and psychosocial evaluations, general work-up with laboratory studies, and
      immunizations-are outlined. This article reviews the medical aspects of
      intercountry adoption for adoptive parents in the United States. The osteopathic
      approach of caring for the whole family lends itself to advising families on
      intercountry adoptions.

PMID- 18057223
TI  - Rhinocerebral mucormycosis acquired after a short course of prednisone therapy.
AB  - Rhinocerebral mucormycosis is a rapidly progressive and often fatal infection
      frequently seen in patients with uncontrolled diabetes mellitus and hematologic
      malignancies. The disease is difficult to diagnose because it often masquerades
      as bacterial sinusitis. The current report describes a 69-year-old white woman
      with diabetes mellitus who was prescribed high-dose prednisone therapy for
      chronic obstructive pulmonary disease. Two weeks after treatment initiation, she
      presented to the hospital with facial edema on the right side, mouth pain, and
      general weakness. No black eschars on the nasal mucosae or palates were present
      on admission. Although bacterial etiology was initially suspected, surgery and
      tissue samples revealed the presence of rhinocerebral mucormycosis. The patient
      died at 6 days postadmission despite aggressive medical and surgical
      intervention. The current report discusses the risk factors associated with
      rhinocerebral mucormycosis as well as the necessity of early diagnosis and
      treatment to improve patient outcomes.

PMID- 18057224
TI  - Evolution of osteopathic graduate medical education: integration of osteopathic
      principles and practice in postdoctoral training.
AB  - Osteopathic principles and practice (OPP) are considered the core, distinguishing
      elements of the osteopathic medical profession. As such, the American Osteopathic
      Association introduced Osteopathic Postdoctoral Training Institutions (OPTIs) in
      1995 to further incorporate OPP into osteopathic graduate medical education. The
      current study describes the evolution of the OPP teaching programs at the West
      Virginia School of Osteopathic Medicine (WVSOM) in Lewisburg in conjunction with
      its OPTI consortium, the Mountain State OPTI. Developments in distance-learning
      technology, lecture and workshop curricula for graduate and undergraduate
      students, and faculty training are described. In addition, elements of
      "telehealth" technology, including administrative support, and trainee and
      student evaluations of the programs are examined. It is hoped that the
      description of WVSOM's curricular evolution and the emphasis on meeting the needs
      of OPP program attendees will assist other osteopathic medical schools in
      developing their own unique OPP programs.

PMID- 18057225
TI  - Relationships between clinical rotation subscores, COMLEX-USA examination
      results, and school-based performance measures.
AB  - At the West Virginia School of Osteopathic Medicine (WVSOM) in Lewisburg, an
      electronic rating form was created to assist preceptors in evaluating student
      performance for third- and fourth-year clinical rotations. Multiple preceptors,
      often in rural locations, rated the clinical performance of 70 students in the
      WVSOM graduating class of 2005. The current study analyzes these ratings. Using
      Cronbach alpha, subscore reliability coefficients were obtained for all
      rotations: clinical knowledge, 0.80; data collection, 0.59; application of
      knowledge, 0.65; and professionalism, 0.78. For the three required family
      medicine rotations, which were almost always supervised by osteopathic
      physicians, reliability of the rating for osteopathic principles and practice
      (OPP) was 0.44. Intercorrelations among these five subscores ranged from 0.46 to
      0.94, all statistically significant at the .01 level. Ratings for the five
      subscores were compared with 19 measures of student performance in other parts of
      the WVSOM curriculum, many correlations were significant at the .01 level.
      Clinical knowledge correlated 0.59 with year 2 grade point average (GPA), 0.51
      with years 1 and 2 OPP GPA, 0.50 with Comprehensive Osteopathic Medical Licensing
      Examination USA Level 2 Cognitive Evaluation, and 0.45 with years 1 and 2
      physical diagnosis GPA. Application of knowledge correlated 0.55 with year 2 GPA
      and 0.50 with the organization score on the college's year 3 objective structured
      clinical evaluation. Professionalism correlated 0.51 with year 2 GPA and 0.49
      with OPP years 1 and 2 written examination score. The average preceptor rating
      using the new electronic form was 92.6, compared with 96.8 when the previous
      paper-based form was used for the WVSOM class of 1998 (change significant at .05
      level). These moderate correlations provide some support for the validity of the
      Clinical Education Grade Form.

PMID- 18057227
TI  - Clinical molecular imaging in intestinal graft-versus-host disease: mapping of
      disease activity, prediction, and monitoring of treatment efficiency by positron
      emission tomography.
AB  - Gastrointestinal graft-versus-host disease (GVHD) is a common and potentially
      life-threatening complication after allogeneic hematopoietic stem-cell
      transplantation (HSCT). Noninvasive tests for assessment of GVHD activity are
      desirable but lacking. In the present study, we were able to visualize intestinal
      GVHD-associated inflammation in an allogeneic murine transplantation model by
      (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in vivo. A
      predominant localization of intestinal GVHD to the colon was verified by
      histology and fluorescence reflectance imaging of enhanced green fluorescent
      protein (EGFP)-expressing donor cells. Colonic infiltration by EGFP(+) donor
      lymphocytes matched increased FDG uptake in PET examinations. These preclinical
      data were prospectively translated into 30 patients with suspected intestinal
      GVHD beyond 20 days after transplantation. A total of 14 of 17 patients with a
      diagnostic histology showed significant FDG uptake of the gut, again
      predominantly in the colon. No increased FDG uptake was detected in 13 patients
      without histologic evidence of intestinal GVHD. Our findings indicate that FDG
      PET is a sensitive and specific noninvasive imaging technique to assess
      intestinal GVHD, map its localization, and predict and monitor treatment
      responsiveness. Novel targeted tracers for PET may provide new insights into the
      pathophysiology of GVHD and bear the potential to further improve GVHD diagnosis.

PMID- 18057226
TI  - Maurer's clefts of Plasmodium falciparum are secretory organelles that
      concentrate virulence protein reporters for delivery to the host erythrocyte.
AB  - In blood-stage infection by the human malaria parasite Plasmodium falciparum,
      export of proteins from the intracellular parasite to the erythrocyte is key to
      virulence. This export is mediated by a host-targeting (HT) signal present on a
      "secretome" of hundreds of parasite proteins engaged in remodeling the
      erythrocyte. However, the route of HT-mediated export is poorly understood. Here
      we show that minimal soluble and membrane protein reporters that contain the HT
      motif and mimic export of endogenous P falciparum proteins are detected in the
      lumen of "cleft" structures synthesized by the pathogen. Clefts are efficiently
      targeted by the HT signal. Furthermore, the HT signal does not directly
      translocate across the parasitophorous vacuolar membrane (PVM) surrounding the
      parasite to deliver protein to the erythrocyte cytoplasm, as suggested by current
      models of parasite protein trafficking to the erythrocyte. Rather, it is a
      lumenal signal that sorts protein into clefts, which then are exported beyond the
      PVM. These data suggest that Maurer's clefts, which are unique to the virulent P
      falciparum species, are pathogen-induced secretory organelles that concentrate HT
      containing soluble and membrane parasite proteins in their lumen for delivery to
      the host erythrocyte.

PMID- 18057228
TI  - CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective
      pharmacologic profile competitive with bortezomib.
AB  - Modulating protein ubiquitination via proteasome inhibition represents a
      promising target for cancer therapy, because of the higher sensitivity of cancer
      cells to the cytotoxic effects of proteasome inhibition. Here we show that CEP
      18770 is a novel orally-active inhibitor of the chymotrypsin-like activity of the
      proteasome that down-modulates the nuclear factor-kappaB (NF-kappaB) activity and
      the expression of several NF-kappaB downstream effectors. CEP-18770 induces
      apoptotic cell death in multiple myeloma (MM) cell lines and in primary purified
      CD138-positive explant cultures from untreated and bortezomib-treated MM
      patients. In vitro, CEP-18770 has a strong antiangiogenic activity and potently
      represses RANKL-induced osteoclastogenesis. Importantly, CEP-18770 exhibits a
      favorable cytotoxicity profile toward normal human epithelial cells, bone marrow
      progenitors, and bone marrow-derived stromal cells. Intravenous and oral
      administration of CEP-18770 resulted in a more sustained pharmacodynamic
      inhibition of proteasome activity in tumors relative to normal tissues, complete
      tumor regression of MM xenografts and improved overall median survival in a
      systemic model of human MM. Collectively, these findings provide evidence for the
      utility of CEP-18770 as a novel orally active proteasome inhibitor with a
      favorable tumor selectivity profile for the treatment of MM and other
      malignancies responsive to proteasome inhibition.

PMID- 18057229
TI  - A dyskerin motif reactivates telomerase activity in X-linked dyskeratosis
      congenita and in telomerase-deficient human cells.
AB  - Dyskerin gene is mutated in patients with X-linked dyskeratosis congenita (X-DC),
      which results in greatly reduced levels of telomerase activity. A genetic
      suppressor element (GSE) termed GSE24-2 has been isolated in a screening for
      cisplatin resistance. GSE24-2-expressing cells presented impaired telomerase
      inhibition following in vitro exposure to chemotherapies, such as cisplatin, or
      telomerase inhibitors. The promoter of the telomerase component hTERT was
      constitutively activated in GSE24-2 cells in a c-myc expression-dependent manner.
      Deletion analyses and mutagenesis of the human c-myc promoter demonstrated that
      the target sequence for activation was the nuclease hypersensitive element-III
      (NHEIII) site located upstream to the P1 region of the promoter. Further,
      expression of GSE24-2 in cell lines derived from patients with X-DC and in VA13
      cells induced increased hTERT RNA and hTR levels and recovery of telomerase
      activity. Finally, expression of GSE24-2 was able to rescue X-DC fibroblasts from
      premature senescence. These data demonstrate that this domain of dyskerin plays
      an important role in telomerase maintenance following cell insults such as
      cisplatin treatment, and in telomerase-defective cells in patients with X-DC. The
      expression of this dyskerin fragment has a dominant function in X-DC cells and
      could provide the basis for a therapeutic approach to this disease.

PMID- 18057230
TI  - Biologic and molecular effects of granulocyte colony-stimulating factor in
      healthy individuals: recent findings and current challenges.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used
      in healthy donors for collection of peripheral blood progenitor cells (PBPCs) for
      allogeneic transplantation and granulocytes for transfusion. The spectrum of its
      biologic and molecular activities in healthy individuals is coming into sharper
      focus, creating a unique set of challenges and clarifying the need to monitor and
      safeguard donor safety. Accumulating evidence indicates that rhG-CSF effects are
      not limited to the myeloid cell lineage. This may reflect the presence of
      functional G-CSF receptors on other cell types and tissues, as well as rhG-CSF
      induced modulation of cytokine networks. While most rhG-CSF-induced effects are
      transient and self-limiting, preliminary, provocative data have suggested the
      possibility of a more durable effect on the chromosomal integrity of lymphocytes.
      While these reports have not been validated and have been subject to criticism,
      they are prompting prospective studies and monitoring efforts to determine
      whether there is a significant risk of long-term adverse events (eg, hematologic
      malignancies) in healthy PBPC and granulocyte donors. Based on the totality of
      information that is currently available, the administration of rhG-CSF to healthy
      donors for the purpose of PBPC donation continues to have a favorable risk
      benefit profile.

PMID- 18057231
TI  - Melon chlorotic leaf curl virus: characterization and differential reassortment
      with closest relatives reveal adaptive virulence in the squash leaf curl virus
      clade and host shifting by the host-restricted bean calico mosaic virus.
AB  - The genome components of the Melon chlorotic leaf curl virus (MCLCuV) were cloned
      from symptomatic cantaloupe leaves collected in Guatemala during 2002. The MCLCuV
      DNA-A and DNA-B components shared their closest nucleotide identities among
      begomoviruses, at approximately 90 and 81%, respectively, with a papaya isolate
      of MCLCuV from Costa Rica. The closest relatives at the species level were other
      members of the Squash leaf curl virus (SLCV) clade, which is endemic in the
      southwestern United States and Mexico. Biolistic inoculation of cantaloupe
      seedlings with the MCLCuV DNA-A and -B components resulted in the development of
      characteristic disease symptoms, providing definitive evidence of causality.
      MCLCuV experimentally infected species within the Cucurbitaceae, Fabaceae, and
      Solanaceae. The potential for interspecific reassortment was examined for MCLCuV
      and its closest relatives, including the bean-restricted Bean calico mosaic virus
      (BCaMV), and three other cucurbit-infecting species, Cucurbit leaf crumple virus
      (CuLCrV), SLCV, and SMLCV. The cucurbit viruses have distinct but overlapping
      host ranges. All possible reassortants were established using heterologous
      combinations of the DNA-A or DNA-B components. Surprisingly, only certain
      reassortants arising from MCLCuV and BCaMV, or MCLCuV and CuLCrV, were viable in
      bean, even though it is a host of all of the "wild-type" (parent) viruses. The
      bean-restricted BCaMV was differentially assisted in systemically infecting the
      cucurbit test species by the components of the four cucurbit-adapted
      begomoviruses. In certain heterologous combinations, the BCaMV DNA-A or -B
      component was able to infect one or more cucurbit species. Generally, the
      reassortants were less virulent in the test hosts than the respective wild-type
      (parent) viruses, strongly implicating adaptive modulation of virulence. This is
      the first illustration of reassortment resulting in the host range expansion of a
      host-restricted begomovirus.

PMID- 18057232
TI  - Latent membrane protein 2B regulates susceptibility to induction of lytic Epstein
      Barr virus infection.
AB  - The B-lymphotropic Epstein-Barr virus (EBV) encodes two isoforms of latent
      membrane protein 2 (LMP2), LMP2A and LMP2B, which are expressed during latency in
      B cells. The function of LMP2B is largely unknown, whereas LMP2A blocks B-cell
      receptor (BCR) signaling transduction and induction of lytic EBV infection,
      thereby promoting B-cell survival. Transfection experiments on LMP2B in EBV
      negative B cells and the silencing of LMP2B in EBV-harboring Burkitt's lymphoma
      derived Akata cells suggest that LMP2B interferes with the function of LMP2A, but
      the role of LMP2B in the presence of functional EBV has not been established.
      Here, LMP2B, LMP2A, or both were overexpressed in EBV-harboring Akata cells to
      study the function of LMP2B. The overexpression of LMP2B increased the magnitude
      of EBV switching from its latent to its lytic form upon BCR cross-linking, as
      indicated by a more-enhanced upregulation and expression of EBV lytic genes and
      significantly increased production of transforming EBV compared to Akata vector
      control cells or LMP2A-overexpressing cells. Moreover, LMP2B lowered the degree
      of BCR cross-linking required to induce lytic EBV infection. Finally, LMP2B
      colocalized with LMP2A as demonstrated by immunoprecipitation and
      immunofluorescence and restored calcium mobilization upon BCR cross-linking, a
      signaling process inhibited by LMP2A. Thus, our findings suggest that LMP2B
      negatively regulates the function of LMP2A in preventing the switch from latent
      to lytic EBV replication.

PMID- 18057233
TI  - An integrative bioinformatic approach for studying escape mutations in human
      immunodeficiency virus type 1 gag in the Pumwani Sex Worker Cohort.
AB  - Human immunodeficiency virus type 1 (HIV-1) is able to evade the host cytotoxic T
      lymphocyte (CTL) response through a variety of escape avenues. Epitopes that are
      presented to CTLs are first processed in the presenting cell in several steps,
      including proteasomal cleavage, transport to the endoplasmic reticulum, binding
      by the HLA molecule, and finally presentation to the T-cell receptor. An
      understanding of the potential of the virus to escape CTL responses can aid in
      designing an effective vaccine. To investigate such a potential, we analyzed HIV
      1 gag from 468 HIV-1-positive Kenyan women by using several bioinformatic
      approaches that allowed the identification of positively selected amino acids in
      the HIV-1 gag region and study of the effects that these mutations could have on
      the various stages of antigen processing. Correlations between positively
      selected residues and mean CD4 counts also allowed study of the effect of
      mutation on HIV disease progression. A number of mutations that could create or
      destroy proteasomal cleavage sites or reduce binding affinity of the transport
      antigen processing protein, effectively hindering epitope presentation, were
      identified. Many mutations correlated with the presence of specific HLA alleles
      and with lower or higher CD4 counts. For instance, the mutation V190I in subtype
      A1-infected individuals is associated with HLA-B*5802 (P = 4.73 x 10(-4)), a
      rapid-progression allele according to other studies, and also to a decreased mean
      CD4 count (P = 0.019). Thus, V190I is a possible HLA escape mutant. This method
      classifies many positively selected mutations across the entire gag region
      according to their potential for immune escape and their effect on disease
      progression.

PMID- 18057234
TI  - Activation of p90 ribosomal S6 kinase by ORF45 of Kaposi's sarcoma-associated
      herpesvirus and its role in viral lytic replication.
AB  - The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase
      (MAPK) pathway is essential for infection by a variety of viruses. The p90
      ribosomal S6 kinases (RSKs) are direct substrates of ERK and functional mediators
      of ERK MAPK signaling, but their roles in viral infection have never been
      examined. We demonstrate that ORF45 of Kaposi's sarcoma-associated herpesvirus
      (KSHV) interacts with RSK1 and RSK2 and strongly stimulates their kinase
      activities. The activation of RSK by ORF45 is correlated with ERK activation but
      does not require MEK. We further demonstrate that RSK1/RSK2 is activated during
      KSHV primary infection and reactivation from latency; a subset of RSK1/RSK2 is
      present in the viral replication compartment in the nucleus. Depletion of
      RSK1/RSK2 by small interfering RNA or the specific inhibitor BI-D1870 suppresses
      KSHV lytic gene expression and progeny virion production, suggesting an essential
      role of RSK1/RSK2 in KSHV lytic replication.

PMID- 18057235
TI  - Kaposi's sarcoma-associated herpesvirus induces sustained levels of vascular
      endothelial growth factors A and C early during in vitro infection of human
      microvascular dermal endothelial cells: biological implications.
AB  - Kaposi's sarcoma (KS), a vascular tumor associated with human immunodeficiency
      virus type 1 infection, is characterized by spindle-shaped endothelial cells,
      inflammatory cells, cytokines, growth and angiogenic factors, and angiogenesis.
      KS spindle cells are believed to be of the lymphatic endothelial cell (LEC) type.
      Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8) is
      etiologically linked to KS, and in vitro KSHV infection of primary human dermal
      microvascular endothelial cells (HMVEC-d) is characterized by the induction of
      preexisting host signal cascades, sustained expression of latency-associated
      genes, transient expression of a limited number of lytic genes, sustained
      induction of NF-kappaB and several cytokines, and growth and angiogenic factors.
      KSHV induced robust vascular endothelial growth factor A (VEGF-A) and VEGF-C gene
      expression as early as 30 min postinfection (p.i.) in serum-starved HMVEC-d,
      which was sustained throughout the observation period of 72 h p.i. Significant
      amounts of VEGF-A and -C were also detected in the culture supernatant of
      infected cells. VEGF-A and -C were also induced by UV-inactivated KSHV and
      envelope glycoprotein gpK8.1A, thus suggesting a role for virus entry stages in
      the early induction of VEGF and requirement of KSHV viral gene expression for
      sustained induction. Exogenous addition of VEGF-A and -C increased KSHV DNA entry
      into target cells and moderately increased latent ORF73 and lytic ORF50 promoter
      activation and gene expression. KSHV infection also induced the expression of
      lymphatic markers Prox-1 and podoplanin as early as 8 h p.i., and a paracrine
      effect was seen in the neighboring uninfected cells. Similar observations were
      also made in the pure blood endothelial cell (BEC)-TIME cells, thus suggesting
      that commitment to the LEC phenotype is induced early during KSHV infection of
      blood endothelial cells. Treatment with VEGF-C alone also induced Prox-1
      expression in the BEC-TIME cells. Collectively, these studies show that the in
      vitro microenvironments of KSHV-infected endothelial cells are enriched, with
      VEGF-A and -C molecules playing key roles in KSHV biology, such as increased
      infection and gene expression, as well as in angiogenesis and lymphangiogenesis,
      thus recapitulating the microenvironment of early KS lesions.

PMID- 18057236
TI  - Functional analysis of the murine cytomegalovirus chemokine receptor homologue
      M33: ablation of constitutive signaling is associated with an attenuated
      phenotype in vivo.
AB  - The murine cytomegalovirus (MCMV) M33 gene is conserved among all
      betaherpesviruses and encodes a homologue of seven-transmembrane receptors (7TMR)
      with the capacity for constitutive signaling. Previous studies have demonstrated
      that M33 is important for MCMV dissemination to or replication within the
      salivary glands. In this study, we probed N- and C-terminal regions of M33 as
      well as known 7TMR signature motifs in transmembrane (TM) II and TM III to
      determine the impact on cell surface expression, constitutive signaling, and in
      vivo phenotype. The region between amino acids R(340) and A(353) of the C
      terminus was found to be important for CREB- and NFAT-mediated signaling,
      although not essential for phosphatidylinositol turnover. Tagging or truncation
      of the N terminus of M33 resulted in loss of cell surface expression. Within TM
      II, an F79D mutation abolished constitutive signaling, demonstrating a role, as
      in other cellular and viral 7TMR, of TM II in receptor activation. In TM III, the
      arginine (but not the asparagine) residue of the NRY motif (the counterpart of
      the common DRY motif in cellular 7TMR) was found to be essential for constitutive
      signaling. Selected mutations incorporated into recombinant MCMV showed that
      disruption of constitutive signaling for a viral 7TMR homologue resulted in a
      reduced capacity to disseminate to or replicate in the salivary glands. In
      addition, HCMV UL33 was found to partially compensate for the lack of M33 in
      vivo, suggesting conserved biological roles of the UL33 gene family.

PMID- 18057237
TI  - Equine infectious anemia virus entry occurs through clathrin-mediated
      endocytosis.
AB  - Entry of wild-type lentivirus equine infectious anemia virus (EIAV) into cells
      requires a low-pH step. This low-pH constraint implicates endocytosis in EIAV
      entry. To identify the endocytic pathway involved in EIAV entry, we examined the
      entry requirements for EIAV into two different cells: equine dermal (ED) cells
      and primary equine endothelial cells. We investigated the entry mechanism of
      several strains of EIAV and found that both macrophage-tropic and tissue culture
      adapted strains utilize clathrin-coated pits for entry. In contrast, a
      superinfecting strain of EIAV, EIAV(vMA-1c), utilizes two mechanisms of entry. In
      cells such as ED cells that EIAV(vMA-1c) is able to superinfect, viral entry is
      pH independent and appears to be mediated by plasma membrane fusion, whereas in
      cells where no detectable superinfection occurs, EIAV(vMA-1c) entry that is low
      pH dependent occurs through clathrin-coated pits in a manner similar to wild-type
      virus. Regardless of the mechanism of entry being utilized, the internalization
      kinetics of EIAV is rapid with 50% of cell-associated virions internalizing
      within 60 to 90 min. Cathepsin inhibitors did not prevent EIAV entry, suggesting
      that the low-pH step required by wild-type EIAV is not required to activate
      cellular cathepsins.

PMID- 18057238
TI  - Three-dimensional structure determines the pattern of CD4+ T-cell epitope
      dominance in influenza virus hemagglutinin.
AB  - The structural context of a CD4(+) T-cell epitope is known to influence
      immunodominance at the level of antigen processing, but general rules have not
      emerged. Dominant epitopes of influenza virus hemagglutinin are found to be
      localized to the C-terminal flanks of conformationally stable segments identified
      by low crystallographic B-factors or high COREX residue stabilities. The bias
      toward C-terminal flanks is distinctive for antigens from the influenza virus.
      Dominant epitopes in antigens/allergens from other sources also localize to the
      flanks of stable segments but are found on either N- or C-terminal flanks. Thus,
      dominance arises from preferential endoproteolytic nicking between stable
      segments followed by loading of fragment terminal regions into antigen-presenting
      proteins. This mechanism probably arose in order to direct CD4(+) responses onto
      sequences that are conserved for structure and function. Structure-guided
      presentation could enhance protection against genetically drifting influenza
      virus variants but most likely reduces protection against new viral subtypes.

PMID- 18057239
TI  - Hippocampal poly(ADP-Ribose) polymerase 1 and caspase 3 activation in neonatal
      bornavirus infection.
AB  - Infection of neonatal rats with Borna disease virus results in a characteristic
      behavioral syndrome and apoptosis of subsets of neurons in the hippocampus,
      cerebellum, and cortex (neonatal Borna disease [NBD]). In the NBD rat
      hippocampus, dentate gyrus granule cells progressively degenerate. Apoptotic loss
      of granule cells in NBD is associated with accumulation of zinc in degenerating
      neurons and reduced zinc in granule cell mossy fibers. Excess zinc can trigger
      poly(ADP-ribose) polymerase 1 (PARP-1) activation, and PARP-1 activation can
      mediate neuronal death. Here, we evaluate hippocampal PARP-1 mRNA and protein
      expression levels, activation, and cleavage, as well as apoptosis-inducing factor
      (AIF) nuclear translocation and executioner caspase 3 activation, in NBD rats.
      PARP-1 mRNA and protein levels were increased in NBD hippocampi. PARP-1
      expression and activity were increased in granule cell neurons and glia with
      enhanced ribosylation of proteins, including PARP-1 itself. In contrast, levels
      of poly(ADP-ribose) glycohydrolase mRNA were decreased in NBD hippocampi. PARP-1
      cleavage and AIF expression were also increased in astrocytes in NBD hippocampi.
      Levels of activated caspase 3 protein were increased in NBD hippocampi and
      localized to nuclei, mossy fibers, and dendrites of granule cell neurons. These
      results implicate aberrant zinc homeostasis, PARP-1, and caspase 3 activation as
      contributing factors in hippocampal neurodegeneration in NBD.

PMID- 18057240
TI  - Evidence of the recombinant origin of a bat severe acute respiratory syndrome
      (SARS)-like coronavirus and its implications on the direct ancestor of SARS
      coronavirus.
AB  - Bats have been identified as the natural reservoir of severe acute respiratory
      syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous
      studies suggested that none of the currently sampled bat SLCoVs is the descendant
      of the direct ancestor of SCoV, based on their relatively distant phylogenetic
      relationship. In this study, evidence of the recombinant origin of the genome of
      a bat SLCoV is demonstrated. We identified a potential recombination breakpoint
      immediately after the consensus intergenic sequence between open reading frame 1
      and the S coding region, suggesting the replication intermediates may participate
      in the recombination event, as previously speculated for other CoVs. Phylogenetic
      analysis of its parental regions suggests the presence of an uncharacterized
      SLCoV lineage that is phylogenetically closer to SCoVs than any of the currently
      sampled bat SLCoVs. Using various Bayesian molecular-clock models, interspecies
      transfer of this SLCoV lineage from bats to the amplifying host (e.g., civets)
      was estimated to have happened a median of 4.08 years before the SARS outbreak.
      Based on this relatively short window period, we speculate that this
      uncharacterized SLCoV lineage may contain the direct ancestor of SCoV. This study
      sheds light on the possible host bat species of the direct ancestor of SCoV,
      providing valuable information on the scope and focus of surveillance for the
      origin of SCoV.

PMID- 18057241
TI  - Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a,
      a modulator of lymphocyte signaling pathways.
AB  - The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a
      functional homologue of the tumor necrosis factor receptor family and contributes
      substantially to the oncogenic potential of EBV through activation of nuclear
      factor kappaB (NF-kappaB). MicroRNAs (miRNAs) are a class of small RNA molecules
      that are involved in the regulation of cellular processes such as growth,
      development, and apoptosis and have recently been linked to cancer phenotypes.
      Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the
      expression of several cellular miRNAs, including the most highly regulated of
      these, miR-146a. Quantitative reverse transcription-PCR analysis confirmed
      induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV
      latency type III and type I cell lines revealed substantial expression of miR
      146a in type III (which express LMP1) but not in type I cell lines. Reporter
      studies demonstrated that LMP1 induces miR-146a predominantly through two NF
      kappaB binding sites in the miR-146a promoter and identified a role for an Oct-1
      site in conferring basal and induced expression. Array analysis of cellular mRNAs
      expressed in Akata cells transduced with an miR-146a-expressing retrovirus
      identified genes that are directly or indirectly regulated by miR-146a, including
      a group of interferon-responsive genes that are inhibited by miR-146a. Since miR
      146a is known to be induced by agents that activate the interferon response
      pathway (including LMP1), these results suggest that miR-146a functions in a
      negative feedback loop to modulate the intensity and/or duration of the
      interferon response.

PMID- 18057242
TI  - Hepatitis A virus mutant spectra under the selective pressure of monoclonal
      antibodies: codon usage constraints limit capsid variability.
AB  - Severe structural constraints in the hepatitis A virus (HAV) capsid have been
      suggested as the reason for the lack of emergence of new serotypes in spite of
      the occurrence of complex distributions of mutants or quasispecies. Analysis of
      the HAV mutant spectra under immune pressure by the monoclonal antibodies (MAbs)
      K34C8 (immunodominant site) and H7C27 (glycophorin binding site) has revealed
      different evolutionary dynamics. Populations composed of complex ensembles of
      mutants with very low fitness or single dominant mutants with high fitness permit
      the acquisition of resistance to each of the MAbs, respectively. Deletion mutants
      were detected as components of the mutant spectra: up to 61 residues, with an
      average of 19, and up to 83 residues, with an average of 45, in VP3 and VP1
      proteins, respectively. A clear negative selection of those replacements
      affecting the residues encoded by rare codons of the capsid surface has been
      detected through the present quasispecies analysis, confirming a certain
      beneficial role of such clusters. Since these clusters are located near or at the
      epitope regions, the need to maintain such clusters might prevent the emergence
      of new serotypes.

PMID- 18057243
TI  - The c3-v4 region is a major target of autologous neutralizing antibodies in human
      immunodeficiency virus type 1 subtype C infection.
AB  - The early autologous neutralizing antibody response in human immunodeficiency
      virus type 1 (HIV-1) subtype C infections is often characterized by high titers,
      but the response is type specific with little to no cross-neutralizing activity.
      The specificities of these early neutralizing antibodies are not known; however,
      the type specificity suggests that they may target the variable regions of the
      envelope. Here, we show that cross-reactive anti-V3 antibodies developed within 3
      to 12 weeks in six individuals but did not mediate autologous neutralization.
      Using a series of chimeric viruses, we found that antibodies directed at the
      V1V2, V4, and V5 regions contributed to autologous neutralization in some
      individuals, with V1V2 playing a more substantial role. However, these antibodies
      did not account for the total neutralizing capacity of these sera against the
      early autologous virus. Antibodies directed against the C3-V4 region were
      involved in autologous neutralization in all four sera studied. In two sera,
      transfer of the C3-V4 region rendered the chimera as sensitive to antibody
      neutralization as the parental virus. Although the C3 region, which contains the
      highly variable alpha2-helix was not a direct target in most cases, it
      contributed to the formation of neutralization epitopes as substitution of this
      region resulted in neutralization resistance. These data suggest that the C3 and
      V4 regions combine to form important structural motifs and that epitopes in this
      region are major targets of the early autologous neutralizing response in HIV-1
      subtype C infection.

PMID- 18057244
TI  - A premature termination codon mutation at the C terminus of foamy virus Gag
      downregulates the levels of spliced pol mRNA.
AB  - Foamy viruses (FV) comprise a subfamily of retroviruses. Orthoretroviruses, such
      as human immunodeficiency virus type 1, synthesize Gag and Pol from unspliced
      genomic RNA. However, FV Pol is expressed from a spliced mRNA independently of
      Gag. FV pol splicing uses a 3' splice site located at the 3' end of gag,
      resulting in a shared exon between gag and pol. Previously, our laboratory showed
      that C-terminal Gag premature termination codon (PTC) mutations in the 3' shared
      exon led to greatly decreased levels of Pol protein (C. R. Stenbak and M. L.
      Linial, J. Virol. 78:9423-9430, 2004). To further characterize these mutants, we
      quantitated the levels of unspliced gag and spliced pol mRNAs using a real-time
      PCR assay. In some of the PTC mutants, the levels of spliced pol mRNA were
      reduced as much as 30-fold, whereas levels of unspliced gag RNA were not
      affected. Substitutions of a missense codon in place of a PTC restored normal
      levels of spliced pol mRNA. Disrupting Upf proteins involved in nonsense-mediated
      mRNA decay (NMD) did not affect Pol protein expression. Introduction of an exonic
      splicing enhancer downstream of the PTC mutation restored pol splicing to the
      wild-type level. Taken together, our results show that the PTC mutation itself is
      responsible for decreased levels of pol mRNA but that mechanisms other than NMD
      might be involved in downregulating Pol expression. The results also suggest that
      normal pol splicing utilizes a suboptimal splice site seen for other spliced
      mRNAs in most retroviruses, in that introduced exonic enhancer elements can
      increase splicing efficiency.

PMID- 18057245
TI  - Noncanonical TATA sequence in the UL44 late promoter of human cytomegalovirus is
      required for the accumulation of late viral transcripts.
AB  - During productive infection, human cytomegalovirus (HCMV) UL44 transcription
      initiates at three distinct start sites that are differentially regulated. Two of
      the start sites, the distal and the proximal, are active at early times, whereas
      the middle start site is active only at late times after infection. The UL44
      early viral gene product is essential for viral DNA synthesis. The UL44 gene
      product from the late viral promoter affects primarily viral gene expression at
      late times after infection rather than viral DNA synthesis (H. Isomura, M. F.
      Stinski, A. Kudoh, S. Nakayama, S. Iwahori, Y. Sato, and T. Tsurumi, J. Virol.
      81:6197, 2007). The UL44 early viral promoters have a canonical TATA sequence,
      "TATAA." In contrast, the UL44 late viral promoter has a noncanonical TATA
      sequence. Using recombinant viruses, we found that the noncanonical TATA sequence
      is required for the accumulation of late viral transcripts. The GC boxes that
      surround the middle TATA element did not affect the kinetics or the start site of
      UL44 late transcription. Replacement of the distal TATA element with a
      noncanonical TATA sequence did not affect the kinetics of transcription or the
      transcription start site, but it did induce an alternative transcript at late
      times after infection. The data indicate that a noncanonical TATA box is used at
      late times after HCMV infection.

PMID- 18057246
TI  - Cooperative effect of the attenuation determinants derived from poliovirus sabin
      1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse
      infection model.
AB  - Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and
      is also associated with serious neurological disorders. An attenuated EV71 strain
      [EV71(S1-3')] has been established in the cynomolgus monkey infection model; this
      strain contains the attenuation determinants derived from the type 1 poliovirus
      vaccine strain, Sabin 1 [PV1(Sabin)], in the 5' nontranslated region (NTR), 3D
      polymerase, and 3' NTR. In this study, we analyzed the effect of the attenuation
      determinants of PV1(Sabin) on EV71 infection in a NOD/SCID mouse infection model.
      We isolated a mouse-adapted EV71 strain [EV71(NOD/SCID)] that causes paralysis of
      the hind limbs in 3- to 4-week-old NOD/SCID mice by adaptation of the virulent
      EV71(Nagoya) strain in the brains of NOD/SCID mice. A single mutation at
      nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of
      the glycine at position 145 to glutamic acid) was essential for the mouse-adapted
      phenotype in NOD/SCID mice. Next, we introduced attenuation determinants derived
      from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya)
      genome. In 4-week-old mice, the determinants in the 3D polymerase and 3' NTR,
      which are the major temperature-sensitive determinants, had a strong effect on
      attenuation. In contrast, the effect of individual determinants was weak in 3
      week-old NOD/SCID mice, and all the determinants were required for substantial
      attenuation. These results suggest that a cooperative effect of the attenuation
      determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.

PMID- 18057247
TI  - Translocation and colocalization of ICP4 and ICP0 in cells infected with herpes
      simplex virus 1 mutants lacking glycoprotein E, glycoprotein I, or the virion
      host shutoff product of the UL41 gene.
AB  - In wild-type herpes simplex virus 1-infected cells, the major regulatory protein
      ICP4 resides in the nucleus whereas ICP0 becomes dynamically associated with
      proteasomes and late in infection is translocated and dispersed in the cytoplasm.
      Inhibition of proteasomal function results in retention or transport of ICP0 to
      the nucleus. We report that in cells infected with mutants lacking glycoprotein E
      (gE), glycoprotein I (gI), or the product of the U(L)41 gene, both ICP4 and ICP0
      are translocated to the cytoplasm and coaggregate in small dense structures that,
      in the presence of proteasomal inhibitor MG132, also contain proteasomal
      components. Gold particle-conjugated antibody to ICP0 reacted in thin sections
      with dense protein aggregates in the cytoplasm of mutant virus-infected cells.
      Similar aggregates were present in the nuclei but not in the cytoplasm of wild
      type virus-infected cells. Exposure of cells early in infection to MG132 does not
      result in retention of ICP0 as in wild-type virus-infected cells. The results
      suggest that the retention of ICP4 and ICP0 in the nucleus is a dynamic process
      that involves the function of other viral proteins that may include the Fc
      receptor formed by the gE/gI complex and is not merely the consequence of
      expression of a nuclear localization signal. It is noteworthy that in DeltaU(L)41
      infected cells gE is retained in the trans-Golgi network and is not widely
      dispersed in cellular membranes.

PMID- 18057248
TI  - Replication of coxsackievirus B3 in primary cell cultures generates novel viral
      genome deletions.
AB  - Coxsackievirus B3 (CVB3) generates 5'-terminally deleted genomes (TDs) during
      replication in murine hearts. We show here that CVB3 populations with TDs can
      also be generated within two to three passages of CVB3 in primary, but not
      immortalized, cell cultures. Deletions of less than 49 nucleotides increase in
      size during passage, while 5' TDs of 49 nucleotides appear to be the maximum
      deletion size. The cellular environment of contact-inhibited primary cell
      cultures or the myocardium in vivo is sufficient for the selection of 5' TDs over
      undeleted genomes.

PMID- 18057250
TI  - WITHDRAWN: Natural recombination between Newcastle disease virus vaccine strains
      and circulating viruses.
AB  - This article has been retracted.

PMID- 18057249
TI  - Human papillomavirus type 16 and 18 E7-pulsed dendritic cell vaccination of stage
      IB or IIA cervical cancer patients: a phase I escalating-dose trial.
AB  - The safety and immunogenicity of the human papillomavirus type 16 (HPV16) or
      HPV18 (HPV16/18) E7 antigen-pulsed mature dendritic cell (DC) vaccination were
      evaluated for patients with stage IB or IIA cervical cancer. Escalating doses of
      autologous DC (5, 10, and 15 x 10(6) cells for injection) were pulsed with
      recombinant HPV16/18 E7 antigens and keyhole limpet hemocyanin (KLH; an
      immunological tracer molecule) and delivered in five subcutaneous injections at
      21-day intervals to 10 cervical cancer patients with no evidence of disease after
      they underwent radical surgery. Safety, toxicity, delayed-type hypersensitivity
      (DTH) reaction, and induction of serological and cellular immunity against
      HPV16/18 E7 and KLH were monitored. DC vaccination was well tolerated, and no
      significant toxicities were recorded. All patients developed CD4(+) T-cell and
      antibody responses to DC vaccination, as detected by enzyme-linked immunosorbent
      spot (ELISpot) and enzyme-linked immunosorbent assays (ELISA), respectively, and
      8 out of 10 patients demonstrated levels of E7-specific CD8(+) T-cell counts,
      detected by ELISpot during or immediately after immunization, that were increased
      compared to prevaccination baseline levels. The vaccine dose did not predict the
      magnitude of the antibody or T-cell response or the time to detection of HPV16/18
      E7-specific immunity. DTH responses to intradermal injections of HPV E7 antigen
      and KLH were detected for all patients after vaccination. We conclude that HPV E7
      loaded DC vaccination is safe and immunogenic for stage IB or IIA cervical cancer
      patients. Phase II E7-pulsed DC-based vaccination trials with cervical cancer
      patients harboring a limited tumor burden, or who are at significant risk of
      tumor recurrence, are warranted.

PMID- 18057251
TI  - Independent and cooperative antiviral actions of beta interferon and gamma
      interferon against herpes simplex virus replication in primary human fibroblasts.
AB  - Type I and type II interferons (IFNs) act in synergy to inhibit the replication
      of a variety of viruses, including herpes simplex virus (HSV). To understand the
      mechanism of this effect, we have analyzed the transcriptional profiles of
      primary human fibroblast cells that were first treated with IFN-beta1, IFN-gamma,
      or a combination of both and then subsequently infected with HSV-1. We have
      identified two types of synergistic activities in the gene expression patterns
      induced by IFN-beta1 and IFN-gamma that may contribute to inhibition of HSV-1
      replication. The first is defined as "synergy by independent action," in which
      IFN-beta1 and IFN-gamma induce distinct gene categories. The second, "synergy by
      cooperative action," is a term that describes the positive interaction between
      IFN-beta1 and IFN-gamma as defined by a two-way analysis of variance. This form
      of synergy leads to a much higher level of expression for a subset of genes than
      is seen with either interferon alone. The cooperatively induced genes by IFN
      beta1 and IFN-gamma include those involved in apoptosis, RNA degradation, and the
      inflammatory response. Furthermore, the combination of IFN-beta1 and IFN-gamma
      induces significantly more apoptosis and inhibits HSV-1 gene expression and DNA
      replication significantly more than treatment with either interferon alone. Taken
      together, these data suggest that IFN-beta1 and IFN-gamma work both independently
      and cooperatively to create an antiviral state that synergistically inhibits HSV
      1 replication in primary human fibroblasts and that cooperatively induced
      apoptosis may play a role in the synergistic effect on viral replication.

PMID- 18057252
TI  - The heat shock protein 70 cochaperone YDJ1 is required for efficient membrane
      specific flock house virus RNA replication complex assembly and function in
      Saccharomyces cerevisiae.
AB  - The assembly of RNA replication complexes on intracellular membranes is an
      essential step in the life cycle of positive-sense RNA viruses. We have
      previously shown that Hsp90 chaperone complex activity is essential for efficient
      Flock House virus (FHV) RNA replication in Drosophila melanogaster S2 cells. To
      further explore the role of cellular chaperones in viral RNA replication, we used
      both pharmacologic and genetic approaches to examine the role of the Hsp90 and
      Hsp70 chaperone systems in FHV RNA replication complex assembly and function in
      Saccharomyces cerevisiae. In contrast to results with insect cells, yeast
      deficient in Hsp90 chaperone complex activity showed no significant decrease in
      FHV RNA replication. However, yeast with a deletion of the Hsp70 cochaperone YDJ1
      showed a dramatic reduction in FHV RNA replication that was due in part to
      reduced viral RNA polymerase accumulation. Furthermore, the absence of YDJ1 did
      not reduce FHV RNA replication when the viral RNA polymerase and replication
      complexes were retargeted from the mitochondria to the endoplasmic reticulum.
      These results identify YDJ1 as an essential membrane-specific host factor for FHV
      RNA replication complex assembly and function in S. cerevisiae and are consistent
      with known differences in the role of distinct chaperone complexes in organelle
      specific protein targeting between yeast and higher eukaryotes.

PMID- 18057253
TI  - Patterns of CD8+ immunodominance may influence the ability of Mamu-B*08-positive
      macaques to naturally control simian immunodeficiency virus SIVmac239
      replication.
AB  - Certain major histocompatibility complex (MHC) class I alleles are strongly
      associated with control of human immunodeficiency virus and simian
      immunodeficiency virus (SIV). CD8(+) T cells specific for epitopes restricted by
      these molecules may be particularly effective. Understanding how CD8(+) T cells
      contribute to control of viral replication should yield important insights for
      vaccine design. We have recently identified an Indian rhesus macaque MHC class I
      allele, Mamu-B*08, associated with elite control and low plasma viremia after
      infection with the pathogenic isolate SIVmac239. Here, we infected four Mamu-B*08
      positive macaques with SIVmac239 to investigate why some of these macaques
      control viral replication. Three of the four macaques controlled SIVmac239
      replication with plasma virus concentrations below 20,000 viral RNA copies/ml at
      20 weeks postinfection; two of four macaques were elite controllers (ECs).
      Interestingly, two of the four macaques preserved their CD4(+) memory T
      lymphocytes during peak viremia, and all four recovered their CD4(+) memory T
      lymphocytes in the chronic phase of infection. Mamu-B*08-restricted CD8(+) T-cell
      responses dominated the acute phase and accounted for 23.3% to 59.6% of the total
      SIV-specific immune responses. Additionally, the ECs mounted strong and broad
      CD8(+) T-cell responses against several epitopes in Vif and Nef. Mamu-B*08
      specific CD8(+) T cells accounted for the majority of mutations in the virus at
      18 weeks postinfection. Interestingly, patterns of viral variation in Nef
      differed between the ECs and the other two macaques. Natural containment of AIDS
      virus replication in Mamu-B*08-positive macaques may, therefore, be related to a
      combination of immunodominance and viral escape from CD8(+) T-cell responses.

PMID- 18057254
TI  - Replication of beta- and gammaretroviruses is restricted in I/LnJ mice via the
      same genetic mechanism.
AB  - Mice of the I/LnJ inbred strain are unique in their ability to mount a robust and
      sustained humoral immune response capable of neutralizing infection with a
      betaretrovirus, mouse mammary tumor virus (MMTV). Virus-neutralizing antibodies
      (Abs) coat MMTV virions secreted by infected cells, preventing virus spread and
      hence the formation of mammary tumors. To investigate whether I/LnJ mice resist
      infection with other retroviruses besides MMTV, the animals were infected with
      murine leukemia virus (MuLV), a gammaretrovirus. MuLV-infected I/LnJ mice
      produced virus-neutralizing Abs that block virus transmission and virally induced
      disease. Generation of virus-neutralizing Abs required gamma interferon but was
      independent of interleukin-12. This unique mechanism of retrovirus resistance is
      governed by a single recessive gene, virus infectivity controller 1 (vic1),
      mapped to chromosome 17. In addition to controlling the antivirus humoral immune
      response, vic1 is also required for an antiviral cytotoxic response. Both types
      of responses were maintained in mice of the susceptible genetic background but
      congenic for the I/LnJ vic1 locus. Although the vic1-mediated resistance to MuLV
      resembles the mechanism of retroviral recovery controlled by the resistance to
      Friend virus 3 (rfv3) gene, the rfv3 gene has been mapped to chromosome 15 and
      confers resistance to MuLV but not to MMTV. Thus, we have identified a unique
      virus resistance mechanism that controls immunity against two distinct
      retroviruses.

PMID- 18057255
TI  - Cooperative binding of the class I major histocompatibility complex cytoplasmic
      domain and human immunodeficiency virus type 1 Nef to the endosomal AP-1 complex
      via its mu subunit.
AB  - Human immunodeficiency virus type 1 Nef provides immune evasion by decreasing the
      expression of major histocompatibility complex class I (MHC-I) at the surfaces of
      infected cells. The endosomal clathrin adaptor protein complex AP-1 is a key
      cellular cofactor for this activity, and it is recruited to the MHC-I cytoplasmic
      domain (CD) in the presence of Nef by an uncharacterized mechanism. To determine
      the molecular basis of this recruitment, we used an MHC-I CD-Nef fusion protein
      to represent the MHC-I CD/Nef complex during protein interaction assays. The MHC
      I CD had no intrinsic ability to bind AP-1, but it conferred binding activity
      when fused to Nef. This activity was independent of the canonical leucine-based
      AP-binding motif in Nef; it required residue Y320 in the MHC-I CD and residues
      E62-65 and P78 in Nef, and it involved the mu but not the gamma/sigma subunits of
      AP-1. The impaired binding of mutants encoding substitutions of E62-65 or P78 in
      Nef was rescued by replacing the Y320SQA sequence in the MHC-I CD with YSQL,
      suggesting that Nef allows the YSQA sequence to act as if it were a canonical mu
      binding motif. These data identify the mu subunit of AP-1 (mu1) as the key target
      of the MHC-I CD/Nef complex, and they indicate that both Y320 in the MHC-I CD and
      E62-65 in Nef interact directly with mu1. The data support a cooperative binding
      model in which Nef functions as a clathrin-associated sorting protein that allows
      recognition of an incomplete, tyrosine-based mu-binding signal in the MHC-I CD by
      AP-1.

PMID- 18057256
TI  - Genetic recombination between human immunodeficiency virus type 1 (HIV-1) and HIV
      2, two distinct human lentiviruses.
AB  - Human immunodeficiency virus type 1 (HIV-1) and HIV-2 are genetically distinct
      viruses that each can cause AIDS. Approximately 1 million people are infected
      with both HIV-1 and HIV-2. Additionally, these two viruses use the same receptor
      and coreceptors and can therefore infect the same target cell populations. To
      explore potential genetic interactions, we first examined whether RNAs from HIV-1
      and HIV-2 can be copackaged into the same virion. We used modified near-full
      length viruses that each contained a green fluorescent protein gene (gfp) with a
      different inactivating mutation. Thus, a functional gfp could be reconstituted
      via recombination, which was used to detect the copackaging of HIV-1 and HIV-2
      RNAs. The GFP-positive (GFP(+)) phenotype was detected in approximately 0.2% of
      the infection events, which was 35-fold lower than the intrasubtype HIV-1 rates.
      We isolated and characterized 54 GFP(+) single-cell clones and determined that
      all of them contained proviruses with reconstituted gfp. We then mapped the
      general structures of the recombinant viruses and characterized the recombination
      junctions by DNA sequencing. We observed several different recombination
      patterns, including those that had crossovers only in gfp. The most common hybrid
      genomes had heterologous long terminal repeats. Although infrequent, crossovers
      in the viral sequences were also identified. Taken together, our study
      demonstrates that HIV-1 and HIV-2 can recombine, albeit at low frequencies. These
      observations indicate that multiple factors are likely to restrict the generation
      of viable hybrid HIV-1 and HIV-2 viruses. However, considering the large
      coinfected human population and the high viral load in patients, these rare
      events could provide the basis for the generation of novel human immunodeficiency
      viruses.

PMID- 18057257
TI  - Complete in vitro reconstitution of adeno-associated virus DNA replication
      requires the minichromosome maintenance complex proteins.
AB  - Adeno-associated virus (AAV) replicates its DNA exclusively by a leading-strand
      DNA replication mechanism and requires coinfection with a helper virus, such as
      adenovirus, to achieve a productive infection. In previous work, we described an
      in vitro AAV replication assay that required the AAV terminal repeats (the
      origins for DNA replication), the AAV Rep protein (the origin binding protein),
      and an adenovirus-infected crude extract. Fractionation of these crude extracts
      identified replication factor C (RFC), proliferating cell nuclear antigen (PCNA),
      and polymerase delta as cellular enzymes that were essential for AAV DNA
      replication in vitro. Here we identify the remaining factor that is necessary as
      the minichromosome maintenance (MCM) complex, a cellular helicase complex that is
      believed to be the replicative helicase for eukaryotic chromosomes. Thus,
      polymerase delta, RFC, PCNA, and the MCM complex, along with the virally encoded
      Rep protein, constitute the minimal protein complexes required to reconstitute
      efficient AAV DNA replication in vitro. Interfering RNAs targeted to MCM and
      polymerase delta inhibited AAV DNA replication in vivo, suggesting that one or
      more components of the MCM complex and polymerase delta play an essential role in
      AAV DNA replication in vivo as well as in vitro. Our reconstituted in vitro DNA
      replication system is consistent with the current genetic information about AAV
      DNA replication. The use of highly conserved cellular replication enzymes may
      explain why AAV is capable of productive infection in a wide variety of species
      with several different families of helper viruses.

PMID- 18057258
TI  - Transgene expression facilitated by the v-src splice acceptor can impair
      replication kinetics and lead to genomic instability of Rous sarcoma virus-based
      vectors.
AB  - Rous sarcoma virus (RSV) can be used for the simple generation of high-titer
      replication-competent retroviral (RCR) vectors. Retroviruses undergo frequent
      genomic recombination, however, and vectors with reduced replication kinetics are
      rapidly overgrown by mutant forms. Vector design is hence critical to vector
      efficacy. In this study, two different designs of RSV-based RCR vectors were
      evaluated. Vectors in which transgene expression was facilitated by the v-src
      splice acceptor were revealed to have greatly reduced replication kinetics and
      genomic stability in comparison to vectors in which transgene expression was
      mediated by an internal ribosome entry site in the 3' untranslated region.

PMID- 18057260
TI  - AADE7TM Self-care Behaviors: systematic reviews.

PMID- 18057259
TI  - Negative feedback regulation of RIG-I-mediated antiviral signaling by interferon
      induced ISG15 conjugation.
AB  - RIG-I senses intracellular virus-specific nucleic acid structures and initiates
      an antiviral response that induces interferon (IFN) production, which, in turn,
      activates the transcription of RIG-I to increase RIG-I protein levels. Upon
      intracellular poly(I:C) stimulation, however, the levels of RIG-I protein did not
      correlate with the expression patterns of RIG-I transcripts. When the ISG15
      conjugation system was overexpressed, ISG15 was conjugated to RIG-I and cellular
      levels of the unconjugated form of RIG-I decreased. The ISGylation of RIG-I
      reduced levels of both basal and virus-induced IFN promoter activity. Levels of
      unconjugated RIG-I also decreased when 26S proteasome activity was blocked by
      treatment with MG132, ALLN, or Lactacystin. In the presence of MG132, ISG15
      conjugation to RIG-I increased, and hence, the unconjugated form of RIG-I was
      reduced. In Ube1L(-/-) cells, which lack the ability to conjugate ISG15, basal
      levels of both RIG-I protein and transcripts were increased compared to those in
      wild-type cells. As a result, enhanced production of ISGs and enhanced IFN
      promoter activity in Ube1L(-/-) cells were observed, and the phenotype was
      restored to that of wild-type cells by the overexpression of Ube1L. Based on
      these results, we propose a novel negative feedback loop which adjusts the
      strength of the RIG-I-mediated antiviral response and IFN production through the
      regulation of RIG-I protein by IFN-induced ISG15 conjugation.

PMID- 18057263
TI  - Diabetes and healthy eating: a systematic review of the literature.
AB  - PURPOSE: The purpose of this study is to review the literature on healthy eating
      interventions within diabetes care. DATA SOURCES: The databases PubMed,
      Cumulative Index to Nursing and Allied Health Literature, and PsycINFO were
      searched for the terms healthy eating or dietary and intervention and diabetes in
      the abstracts. In addition, electronic searches of the contents of Diabetes,
      Clinical Diabetes, Diabetes Care, Diabetes Spectrum, and Diabetic Medicine were
      conducted. STUDY SELECTION: Articles were included in the review if the
      participants were diagnosed with type 1 or type 2 diabetes, results from an
      intervention to promote dietary change were reported, measurements were taken
      from 2 time points (preintervention and postintervention), at least 1 outcome
      measured eating behavior, and the articles had been published between 1990 and
      the present date. DATA EXTRACTION: Data were extracted from the 23 studies found
      to be eligible. Studies were compared in terms of sample types and sizes,
      duration, and type and content of intervention. DATA SYNTHESIS: Comparisons were
      made between the characteristics of those studies that produced a statistically
      significant result and those that did not, for the different outcome measures.
      CONCLUSIONS: For studies measuring the outcomes of weight, fat intake, saturated
      fat intake, and carbohydrates, there was a tendency for successful interventions
      to include an exercise dimension and group work. Some outcomes had a tendency to
      show significant changes in studies of longer duration (eg, serum cholesterol),
      whereas others were more likely to show significant changes in studies of shorter
      duration (eg, weight, fiber), suggesting that certain outcomes may be more
      difficult to maintain. Future research would benefit by ensuring that sample
      sizes are adequate to give sufficient power, and interventions should be designed
      that focus on the maintenance in addition to the initiation of eating behavior
      change.

PMID- 18057265
TI  - Interventions for being active among individuals with diabetes: a systematic
      review of the literature.
AB  - PURPOSE: The purpose of this systematic review is to assess and summarize
      evidence and gaps in the literature regarding the intervention for being active
      (exercise) among individuals with diabetes. METHODS: Twelve electronic databases
      were searched. Publications eligible for inclusion specifically studied learning,
      behavioral, clinical, and humanistic outcomes for exercise interventions in adult
      patients with type 1 and type 2 diabetes. RESULTS: Seven reviews (2 systematic
      reviews, 3 meta-analyses, 2 technical reviews) and 34 individual, nonreview
      studies (18 randomized controlled trials, 16 nonrandomized trials) met inclusion
      criteria. For type 2 diabetes, findings suggested that exercise had a positive
      effect on glycemic control and decreased cardiovascular risk, but the impact of
      exercise on behavioral and humanistic outcomes was unclear; long-term outcomes
      and adherence to exercise interventions is unknown because most studies were of
      short duration. The overall impact of varied types of exercise in type 1 diabetes
      was unclear, especially regarding glycemic control. Potential benefits of
      exercise in type 1 may include improved cardiovascular health. CONCLUSION: The
      review did not identify specific successful intervention details because of the
      heterogeneity of studies, subjects, and research gaps. General findings suggest
      that physical activity is better than no exercise at all; intensive regimens, if
      tolerated by patients, achieved better clinical outcomes than less intensive
      regimens. Reviewed studies using structured exercise regimens exhibited a more
      significant impact on outcomes. Substantial gaps in the literature include
      studies measuring direct effects of exercise in the US minority populations most
      affected by type 2 diabetes and economic evaluations of exercise interventions.
      Interventions must be tailored to individual patient needs to succeed.

PMID- 18057267
TI  - Does patient blood glucose monitoring improve diabetes control? A systematic
      review of the literature.
AB  - OBJECTIVE: The purpose of this systematic review was 2-fold: first, to perform a
      comprehensive review of relevant studies on the impact of self-monitoring of
      blood glucose (SMBG) on HbA1c levels for patients with type 2 diabetes mellitus
      and, second, to explore mediators and moderators within a self-regulation
      framework. DATA SOURCES: Five databases-Medline, PsychInfo, Cochrane Database of
      Systematic Reviews, Cochrane Central Register of Controlled Trials, and
      Cumulative Index to Nursing & Allied Health Literature (CINAHL)-were searched.
      STUDY SELECTION: Cross-sectional, longitudinal, and randomized control trials
      from 1990 to 2006, which included patients with type 2 diabetes not on insulin,
      were reviewed. In total, 6,769 studies were screened for inclusion, 89 were
      retrieved for detailed analysis, and 29 met criteria for inclusion in the review.
      DATA EXTRACTION: Data on the impact of SMBG on HbA1c, potential mediators and
      moderators, study design and participants, and limitations of each study were
      retrieved. DATA SYNTHESIS: Twenty-nine studies were included in this review: 9
      cross-sectional studies, 9 longitudinal studies, and 11 randomized controlled
      trials. Evidence from the cross-sectional and longitudinal studies was
      inconclusive. Evidence from randomized controlled trials suggests that SMBG may
      lead to improvements in glucose control. Very few studies examined potential
      mediators or moderators of SMBG on HbA1c levels. CONCLUSIONS: SMBG may be
      effective in controlling blood glucose for patients with type 2 diabetes. There
      is a need for studies that implement all the components of the process for self
      regulation of SMBG to assess whether patient use of SMBG will improve HbA1c
      levels.

PMID- 18057270
TI  - Medication taking and diabetes: a systematic review of the literature.
AB  - PURPOSE: The purpose of this systematic review is to evaluate the evidence of the
      challenges and barriers to medication taking (adherence) and to summarize the
      interventions that improve medication taking in type 1 and type 2 diabetes
      mellitus. METHODS: PubMed, the Cochrane Collaborative, and the Health and
      Psychosocial Instruments databases were used to obtain articles identified by
      using the MeSH headings of diabetes, medication, oral hypoglycemic agents, oral
      antihyperglycemic agents, oral antidiabetic agents, insulin, adherence,
      medication taking, compliance, fears, treatment, and electronic monitoring. Only
      articles published in English between 1990 and May 7, 2007, and including
      individuals of all ages with type 1 or type 2 diabetes mellitus were included.
      Retrospective and prospective studies reporting adherence to medications using
      self-report, pill counts, medication possession ratios, and electronic monitoring
      devices were included. Database analyses of prescription records from various
      organizations or countries were included only if adherence to pharmacologic
      therapy was stated. Surveys and questionnaires assessing medication taking were
      also included. The data from the selected literature was abstracted
      independently. The various studies were grouped together based on the type of
      study conducted. Studies were not included if a specific measure of adherence to
      medication was not used or stated. The studies are presented in 3 tables
      according to design. CONCLUSIONS: Several barriers to medication taking have been
      suggested for those with diabetes mellitus, although well-controlled trials to
      confirm and resolve these barriers are limited. Diabetes educators should be
      aware of the common barriers to medication taking (regimen complexity of more
      than 1 diabetes mellitus drug or more than 1 dose daily, depression, and
      remembering doses and refills) and provide screening and support to their
      patients to resolve barriers if they exist. Further studies are needed to test
      specific interventions to improve medication taking in diabetes.

PMID- 18057272
TI  - Problem solving in diabetes self-management and control: a systematic review of
      the literature.
AB  - PURPOSE: The purpose of this systematic review is to assess the published
      literature on problem solving and its associations with diabetes self-management
      and control, as the state of evidence exists. DATA SOURCES: PubMed, PsychINFO,
      and ERIC electronic databases were searched for the years 1990 to the present and
      for English-language articles, and reference lists from included studies were
      reviewed to capture additional studies. STUDY SELECTION: Quantitative and
      qualitative studies that addressed problem solving as a process or strategy for
      diabetes self-management were included. Fifty-two studies met the criteria for
      inclusion. DATA EXTRACTION: Study design, sample characteristics, measures, and
      results were reviewed. DATA SYNTHESIS: Thirty-six studies were quantitative; 16
      were conceptual or qualitative. Studies were classified as addressing the problem
      solving definition/framework, assessment, intervention, or health care
      professional issues. CONCLUSIONS: Problem solving is a multidimensional construct
      encompassing verbal reasoning/rational problem solving, quantitative problem
      solving, and coping. Aspects of problem solving can be assessed using newly
      developed diabetes-specific problem-solving measures for children/adolescents and
      adults. Cross-sectional studies in adults, but not children/adolescents, provide
      consistent evidence of associations between problem solving and A1C level. Only
      25% of problem-solving intervention studies with children/adolescents and 50% of
      interventions with adults reported improvement in A1C. Most intervention studies
      reported an improvement in behaviors, most commonly global adherence in
      children/adolescents and dietary behavior in adults. Methodological limitations
      (noninclusion of problem-solving measures, inadequate descriptions of problem
      solving interventions, homogenous samples) need to be addressed in future
      research to clarify the effect of problem solving on diabetes outcomes, identify
      characteristics of effective interventions, and determine the utility across age
      and racial/ethnic groups.

PMID- 18057274
TI  - Reducing risks in diabetes self-management: a systematic review of the
      literature.
AB  - OBJECTIVE: The purpose of this systematic review was to review published
      literature on risk-reducing interventions as part of diabetes self-management.
      DATA SOURCES: Medline (1990-2007), CINAHL (1990-2007), and Cochrane Central
      Register of Controlled Trials (first quarter 2007) databases were searched.
      Reference lists from included studies were reviewed to identify additional
      studies. STUDY SELECTION: Intervention studies that addressed reducing risks to
      help prevent or minimize diabetes complications were included. DATA EXTRACTION:
      Study design, sample characteristics, interventions, and outcomes were extracted.
      DATA SYNTHESIS: Thirty-three studies, represented by 39 articles, met the
      criteria for inclusion and were classified as smoking cessation (n = 3), eye
      examination (n = 2), foot care (n = 10), oral health (n = 2), vaccination (n =
      1), cardiovascular risk reduction (n = 9), and comprehensive risk reduction (n =
      6). Only 46.3% of the 283 outcomes measured in the 33 studies were significantly
      improved. CONCLUSIONS: Reducing risks involves implementing effective risk
      reduction behaviors to prevent or slow the progression of diabetes complications.
      Recognizing risk factors for complications and what constitutes optimal
      preventive care is an important part of managing diabetes. Intervention studies
      are lacking in some areas of reducing risks. Further studies are needed to test
      specific interventions to reduce the risks of diabetes complications.

PMID- 18057276
TI  - Healthy coping, negative emotions, and diabetes management: a systematic review
      and appraisal.
AB  - PURPOSE: The purpose of this systematic review is to assess the literature
      pertinent to healthy coping in diabetes management and to identify effective or
      promising interventions and areas needing further investigation. METHODS: A
      PubMed search identified 186 articles in English published between January 1,
      1990, and July 31, 2006, addressing diabetes and emotion, quality of life,
      depression, adjustment, anxiety, coping, family therapy, behavior therapy,
      psychotherapy, problem solving, couples therapy, or marital therapy. RESULTS:
      Connections among psychological variables, behavioral factors, coping, metabolic
      control, and quality of life are appreciable and multidirectional. Interventions
      for which well-controlled studies indicate benefits for quality of life and/or
      metabolic control include general self-management, coping/problem-solving
      interventions, stress management, support groups, cognitive-behavioral therapy,
      behavioral family systems therapy, cognitive-analytic therapy, multisystemic
      therapy, medications for depression, and the Pathways intervention integrating
      case management, support of medication, and problem-solving counseling.
      CONCLUSIONS: Psychological, emotional, related behavioral factors, and quality of
      life are important in diabetes management, are worthy of attention in their own
      right, and influence metabolic control. A range of interventions that achieve
      benefits in these areas provide a base for developing versatile programs to
      promote healthy coping.

PMID- 18057279
TI  - Transcatheter therapy for hepatic malignancy: standardization of terminology and
      reporting criteria.
AB  - The field of interventional oncology includes tumor ablation as well as the use
      of transcatheter therapies such as embolization, chemoembolization, and
      radioembolization. Terminology and reporting standards for tumor ablation have
      been developed. The development of standardization of terminology and reporting
      criteria for transcatheter therapies should provide a similar framework to
      facilitate the clearest communication among investigators and provide the
      greatest flexibility in comparing established and emerging technologies. An
      appropriate vehicle for reporting the various aspects of catheter directed
      therapy is outlined, including classification of therapies and procedure terms,
      appropriate descriptors of imaging guidance, and terminology to define imaging
      and pathologic findings. Methods for standardizing the reporting of outcomes
      toxicities, complications, and other important aspects that require attention
      when reporting clinical results are addressed. It is the intention of the group
      that adherence to the recommendations will facilitate achievement of the group's
      main objective: improved precision and communication for reporting the various
      aspects of transcatheter management of hepatic malignancy that will translate to
      more accurate comparison of technologies and results and, ultimately, to improved
      patient outcomes.

PMID- 18057280
TI  - IR safety rounds: forgotten dialysis catheter caps.

PMID- 18057281
TI  - Bilateral hypogastric artery occlusion in endovascular repair of abdominal aortic
      aneurysms and its clinical significance.
AB  - PURPOSE: Endovascular treatment of aortoiliac aneurysms near or involving the
      hypogastric artery (HGA) requires HGA occlusion before endografting to avoid
      retrograde filling of the aneurysm. The purpose of this study is to evaluate
      clinical outcomes of bilateral HGA occlusion and determine if benefits gained by
      endovascular aneurysm repair (EVAR) outweigh the morbidity associated with the
      procedure. MATERIALS AND METHODS: Between 1999 and 2004, 128 patients with
      abdominal aortic aneurysm (AAA) were treated with bifurcated endograft placement.
      Bilateral coverage or embolization of HGAs was performed in 14 patients (10.9%).
      Embolization was achieved by deployment of coils and coverage was accomplished by
      extending the endoprosthesis into the external iliac artery. Clinical follow-up
      and computed tomographic angiography were performed at 1, 3, 6, 9, and 12 months
      and annually thereafter to detect potential aneurysm growth and endoleaks.
      RESULTS: During follow-up (range, 1-72 months), buttock claudication was noted in
      four patients (28.6%), including unilateral claudication in two and bilateral
      claudication in two. One patient experienced claudication longer than 12 months,
      which resolved within 18 months. De novo erectile dysfunction was seen in one
      patient, and pelvic ischemia was not found in any patient. There was no evidence
      of endoleak, aneurysm enlargement, or death associated with HGA occlusion.
      CONCLUSIONS: In our series, complications of bilateral HGA occlusion before EVAR
      were moderate and resolved over time. The benefits gained from EVAR outweigh the
      clinical problems caused by bilateral HGA occlusion, as there are no technical
      complications added to the EVAR procedure.

PMID- 18057282
TI  - Midterm clinical experience with a complex-shaped detachable platinum coil system
      for the treatment of cerebral aneurysms: Trufill DCS Orbit detachable coil system
      registry interim results.
AB  - PURPOSE: To report an interim analysis of the registry data and evaluate the
      performance of Trufill DCS Orbit coils in terms of the stability of initial
      aneurysmal occlusion. MATERIALS AND METHODS: From May 1, 2004, to February 1,
      2006, 291 patients with ruptured or unruptured aneurysms were enrolled in a
      multiple-center global registry from 37 centers in the United States, Europe, and
      Latin America to be treated via endovascular embolization with Trufill DCS Orbit
      detachable platinum coils. Acute and long-term anatomic and clinical data were
      collected and evaluated. RESULTS: Initially, complete obliteration was reported
      in 187 of 300 treated aneurysms (62.3%) for which data were available; one
      treated aneurysm had no initial occlusion data. At follow-up (<or=1 year), 99
      aneurysms were assessed. For 56 aneurysms with initial complete obliteration, 49
      (87.5%) remained stable. The overall grade of occlusion of 99 aneurysms remained
      stable or improved in 81 cases (81.8%). Recanalization was seen in 16.2% of
      aneurysms (15 cases of coil compaction and one case of aneurysm growth); two
      aneurysms (2.0%) had coil migration. Five aneurysms (5.1%) underwent repeat
      treatment. CONCLUSIONS: The use of Trufill DCS Orbit coils for the endovascular
      occlusion of aneurysms allowed a favorable rate of initial complete obliteration,
      high packing density, and aneurysmal stability at follow-up as long as 1 year.
      Longer-term follow-up is needed to determine the long-term stability of
      aneurysmal occlusion.

PMID- 18057283
TI  - Endovenous laser treatment of incompetent below-knee great saphenous veins.
AB  - PURPOSE: To test the hypotheses that below-knee great saphenous vein (GSV) reflux
      after successful ablation of the incompetent above-knee GSV is a cause of
      incomplete clinical success and that endovenous laser treatment (ELT) of the
      incompetent below-knee GSV can safely eliminate persistent symptoms. MATERIALS
      AND METHODS: The author evaluated 576 consecutive ELT procedures of the GSV.
      Fifty ELT procedures in incompetent calf GSVs were included in this study.
      Patients with reflux of the entire GSV were selected. All patients underwent
      clinical and ultrasonographic (US) follow-up. RESULTS: In 16 of the 50
      procedures, ELT was performed in the GSV both above and below the knee in
      separate sessions. In 34 procedures, ELT of the GSV above and below the knee was
      performed at the same session. An 810-nm laser was used at 14 W. The mean energy
      was 82 j/cm (range, 56.4-114 j/cm; standard deviation [SD], 14 j/cm). The mean
      follow-up was 11 months (range, 0-28 months; SD, 7 months). Four paresthesias
      occurred. Medial ankle pain resolved in all patients, and swelling resolved in
      all but six limbs. No recanalization occurred. CONCLUSIONS: Patients with
      incompetence of the entire GSV treated with only ELT of the above-knee GSV
      experienced incomplete relief of medial ankle pain and swelling; however,
      symptomatic relief is obtained safely and effectively with additional ELT of the
      below-knee GSV.

PMID- 18057284
TI  - Impact of C-arm CT on hepatic arterial interventions for hepatic malignancies.
AB  - PURPOSE: To evaluate C-arm computed tomography (CT) and assess its potential
      impact on hepatic arterial interventions. MATERIALS AND METHODS: Between May 2005
      and March 2006, all hepatic arterial interventions for hepatic malignancies were
      retrospectively reviewed. C-arm CT acquisitions were performed as an adjunct to
      conventional digital subtraction angiography (DSA). The number of procedures with
      C-arm CT, the acquisitions per intervention, and the procedure time for all
      interventions were recorded. The added information provided by C-arm CT was
      scored as category 1 (no additional information); category 2 (added information
      without impact on procedure management); or category 3 (added information with
      impact on procedure management). Intervention types included infusions,
      radioembolization, embolization, and chemoembolization. A two-sided, two-sample t
      test was used to compare interventions with and without C-arm CT, and P values
      less than .05 were considered significant. RESULTS: C-arm CT was used in 86 of
      240 interventions (36%) in 135 patients. The mean number of acquisitions per
      study was 1.9 (range, 1-4). Thirty-five interventions (40.7%) were scored as
      category 2 and 16 interventions (18.6%) were scored as category 3.
      Chemoembolization was associated with the highest percentage of C-arm CT
      investigations classified as category 2 and 3 assessed per intervention. The mean
      procedure time was significantly longer (18 minutes) when C-arm CT was used
      (P<.001). CONCLUSIONS: C-arm CT provides additional imaging information beyond
      DSA during hepatic arterial interventions (approximately 60%), and this
      information impacted procedure management in 19% of cases. C-arm CT offers the
      greatest opportunity for additional information during chemoembolization
      procedures and is responsible for a significant but acceptable increase in
      procedure time for this type of hepatic intervention.

PMID- 18057285
TI  - Usefulness of cone-beam volume CT with flat panel detectors in conjunction with
      catheter angiography for transcatheter arterial embolization.
AB  - PURPOSE: To assess the usefulness of cone-beam volume computed tomography (CT)
      (cone-beam CT) with use of flat panel detectors of the direct conversion type in
      conjunction with conventional digital subtraction angiography (DSA) in the
      diagnosis and treatment of patients with hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: Forty-nine consecutive patients (52 suspicious lesions)
      were prospectively examined. All patients underwent intraarterial rotational
      angiography with a flat panel detector system, and the cone-beam CT scans were
      reconstructed from the volume data set. The authors evaluated the diagnostic
      quality of cone-beam CT for the transcatheter arterial chemoembolization (TACE)
      procedure. RESULTS: The diagnostic quality of conventional DSA plus cone-beam CT
      with regard to tumor staining was superior to that of DSA alone. Cone-beam CT
      showed tumor staining in five lesions that were difficult to diagnose with
      confidence on the basis of the DSA findings alone. The extent of contrast medium
      perfusion was sufficiently visualized on all cone-beam CT scans at the tip of the
      catheter positioned in either the segmental or subsegmental hepatic arteries. In
      42 of the 52 lesions (81%), cone-beam CT provided additional useful information
      for therapeutic decision making or TACE compared with DSA. CONCLUSIONS:
      Intraarterial cone-beam CT with a flat panel detector can provide clinically
      acceptable image quality in the assessment of HCC, thereby improving the
      detection of tumor staining due to HCC and the visualization of the extent of
      contrast medium perfusion.

PMID- 18057286
TI  - Transarterial chemoembolization for primary hepatocellular carcinoma in patients
      at high risk.
AB  - PURPOSE: Transarterial chemoembolization (TACE) has become a standard treatment
      option for patients with unresectable hepatocellular carcinoma (HCC). This
      retrospective study evaluated the safety and efficacy of TACE in patients at high
      risk with increased serum bilirubin level, low serum albumin level, poor hepatic
      reserve, or compromised hepatopetal flow in the portal vein (PV). MATERIALS AND
      METHODS: A total of 52 patients underwent 65 high-risk procedures. Thirty
      patients treated with 38 procedures (57.7% of patients and 58.5% of procedures)
      had serum bilirubin levels of 2-3 mg/dL (ie, moderate elevation) and 22 patients
      treated with 27 procedures (42.3% and 41.5%) had a serum bilirubin level of at
      least 3 mg/dL (ie, considerable elevation). Forty patients (76.9%) had serum
      albumin levels less than 3.5 mg/dL. Thirteen recipients of 15 procedures (25% and
      20%) had portal diversion or obstruction. Twenty-four patients (46.2%) had a
      Child-Pugh (CP) score of 8 or less and 28 patients (53.8%) had a CP score of at
      least 9 at the time of TACE. Thirty patients (57.7%) had focal tumors and 22
      patients (42.3%) had multifocal or infiltrative disease. Superselective
      chemoembolization could be performed in 37 procedures (56.9%); lobar
      chemoembolization was performed in the remaining 28 (43.1%). RESULTS: The 30-day
      mortality rate was 7.7% and the procedure-related morbidity rate was 10.8%.
      Patients with multifocal disease and lobar embolization had significantly higher
      mortality rates (P=.03). Individual factors such as serum bilirubin, serum
      albumin, and PV flow did not affect outcomes significantly. The 1- and 2-year
      survival rates in patients with focal disease were 67.9% and 37.7%, respectively,
      compared with 19.6% and 0% in patients with multifocal disease (P<.0001).
      CONCLUSIONS: TACE in patients considered at high risk does not necessarily incur
      a higher incidence of morbidity or mortality. Patient selection should be based
      on extent of disease, and these tumors should be treated selectively at a
      segmental level if possible.

PMID- 18057287
TI  - Percutaneous radiofrequency ablation with a multiple-electrode switching
      generator system.
AB  - PURPOSE: To determine the feasibility and safety of treating 35 hepatic tumors
      with a multiple-electrode switching-generator radiofrequency (RF) ablation
      system. MATERIALS AND METHODS: The authors performed a retrospective review of
      percutaneous RF ablation procedures in 35 hepatic tumors ranging in diameter from
      0.9 to 3.8 cm and involving 22 patients. Tumors smaller than 2 cm were ablated
      with a single electrode, and larger tumors were ablated with two or three
      electrodes depending on tumor size and location of initial electrode placement.
      Electrodes were positioned 1-2 cm apart to create an intratumoral configuration
      that maximized index tumor coverage. Computed tomography or magnetic resonance
      imaging was performed within 24 hours of ablation. The ablation volume, maximum
      ablation size, and maximum tumor size were compared among the three electrode
      groups by using analysis of variance. If the global P value with analysis of
      variance was statistically significant (P<.05), post hoc testing for pairwise
      comparisons was performed by using the Bonferroni correction to adjust for
      multiple comparisons. Complications were defined according to the SIR reporting
      standards for image-guided tumor ablation. RESULTS: Ten tumors were treated with
      one electrode, 16 were treated with two electrodes, and nine were treated with
      three electrodes. The mean and median maximum sizes of the tumors ablated with
      one, two, and three electrodes were 1.2 and 1.1 cm, 2.7 and 2.8 cm, and 3.2 and
      3.4 cm, respectively. The mean and median ablation volumes with two electrodes
      (40.9 and 31.9 cm3, respectively) and three electrodes (59.3 and 48.2 cm3,
      respectively) were significantly greater than that with one electrode (11.7 and
      8.6 cm3, respectively; P<or=.0363 among comparisons). No major complications
      occurred that were directly attributable to the RF ablation procedure. Minor
      complications occurred in two patients (9%). CONCLUSIONS: Percutaneous RF
      ablation of hepatic tumors with a multiple-electrode switching-generator system
      is technically feasible, is safe, and generates ablation volumes greater than
      those seen with a single electrode.

PMID- 18057288
TI  - Covered stent placement in patients with recurrent cancer after a Billroth I
      reconstruction.
AB  - PURPOSE: To assess the technical feasibility and clinical effectiveness of
      covered stent placement in patients with recurrent malignant obstructions after
      Billroth I reconstruction. MATERIALS AND METHODS: From June 1997 to November
      2005, 16 patients underwent covered stent placement for recurrent gastric cancer
      after Billroth I reconstruction. A total of 19 covered stents were used,
      including 14 dual stents and five fully covered stents, as available. RESULTS:
      Stent placement was technically successful in all patients, with 13 of 16
      patients (81%) showing improvement of symptoms. Stent migration occurred in one
      patient, tumor ingrowth in one, and stent collapse and/or bowel perforation in
      one. Nine patients (56%) had concomitant (n=7) or subsequent (n=2) biliary
      obstruction. One patient was lost to follow-up. The remaining 15 patients died 5
      628 days (median, 52 days; mean, 120 days) after stent placement due to
      progression of disease or pneumonia. CONCLUSIONS: Placement of covered metallic
      stents is feasible and effective in patients with recurrent malignant obstruction
      after Billroth I reconstruction.

PMID- 18057289
TI  - Metallic stent placement in patients with recurrent cancer after
      gastrojejunostomy.
AB  - PURPOSE: To assess the technical feasibility and clinical effectiveness of
      placement of expandable metallic stents in patients with recurrent cancer after a
      gastrojejunostomy. MATERIALS AND METHODS: Data from 39 consecutive patients who
      had undergone metallic stent placement for recurrent malignant obstruction after
      a gastrojejunostomy were retrospectively analyzed. Thirty patients underwent a
      distal gastrectomy with a gastrojejunostomy with (n=10) or without (n=20)
      jejunojejunostomy, two patients underwent distal gastrectomy with a Roux-en-Y
      gastrojejunostomy, and seven patients underwent a palliative gastrojejunostomy
      with (n=5) or without (n=2) jejunojejunostomy. A total of 57 metallic stents were
      used in this study: four bare stents, 29 partially covered stents, and 24 fully
      covered stents. Types of obstruction were classified into 12 patterns and types
      of stent placement were classified into 16 patterns. RESULTS: Stent placement was
      technically successful in all patients. After stent placement, 35 of the 39
      patients (90%) experienced improvement of their symptoms, two showed no change,
      and the remaining two showed aggravation of symptoms as a result of faulty stent
      placement. Two patients treated with stent placement only in the afferent loop
      died of aspiration pneumonia. In one of two patients who underwent stent
      placement according to pattern 6, afferent loop syndrome occurred 10 days after
      stent placement and was treated by percutaneous pigtail catheter drainage. Stent
      migration occurred in four of 24 fully covered stents, but in none of the bare or
      partially covered stents. Tumor ingrowth occurred in one of four bare stents,
      tumor overgrowth in one of 29 partially covered stents, and mucosal prolapse in
      one of 24 fully covered stents; all were treated with a second stent placement.
      CONCLUSIONS: Placement of expandable metallic stents in patients with recurrent
      cancer after a gastrojejunostomy seems to be feasible and effective, but accurate
      knowledge of the type of surgical procedure performed and determination of the
      pattern of tumor recurrence are important for successful stent placement.

PMID- 18057290
TI  - Comparison of angiographic CT and spiral CT to assess cement distribution after
      vertebral augmentation.
AB  - PURPOSE: To compare angiographic computed tomographic (CT) imaging with standard
      spiral CT imaging for the depiction of extraosseous cement after vertebral
      augmentation. MATERIALS AND METHODS: Retrospective analysis of 28 consecutive
      patients treated with vertebral augmentation for compression fracture was
      conducted. Intraprocedural angiographic CT and postprocedural spiral CT images
      were acquired in all patients. Angiographic CT and spiral CT images were
      evaluated independently by two experienced radiologists. RESULTS: All vertebral
      augmentation procedures were performed successfully. All observed cement leaks
      were small, and no patient underwent additional treatment for cement leak. One
      level was excluded as a result of severe motion artifacts that rendered
      angiographic CT nondiagnostic. Further analysis was performed in the remaining 27
      patients (12 men; mean age, 62 years; age range, 31-87 y) corresponding to 48
      vertebral levels. Seventeen patients were treated under general anesthesia (33
      levels) and 11 were treated under conscious sedation (15 levels). To detect the
      presence of extraosseous cement, angiographic CT achieved sensitivity of 0.70 and
      0.57 for reader 1 and reader 2, respectively, and specificity of 0.93 and 0.92,
      respectively. Stratified analyses by anesthesia type showed sensitivity of 0.73
      and 0.50, respectively, for conscious sedation versus 0.67 and 0.62,
      respectively, for general anesthesia. Specificity was 1.00 and 1.00,
      respectively, versus 0.92 and 0.90, respectively. CONCLUSIONS: Cement leaks were
      detected with a high specificity and a moderate sensitivity with angiographic CT.
      No difference was found between treatments with general anesthesia versus
      intravenous conscious sedation.

PMID- 18057291
TI  - In vivo efficiency of multipolar radiofrequency ablation with two bipolar
      electrodes: a comparative experimental study in pig kidney.
AB  - PURPOSE: To compare in vivo efficacy of multipolar radiofrequency (RF) ablation
      with two internally cooled electrodes to that of monopolar RF ablation with
      internally cooled single and cluster needles to induce coagulation in in vivo
      porcine kidneys. MATERIALS AND METHODS: Twenty-four coagulations were created in
      the kidneys of 12 pigs by means of laparotomy by using a monopolar or multipolar
      RF system. In the monopolar mode, RF was applied to a single internally cooled
      probe (group A) or to a cluster probe (group B) for 12 minutes. In the multipolar
      mode, RF was applied to two bipolar probes with 2-cm interprobe spacing up to 50
      kJ (group C). Technical parameters and the dimensions, shapes, and coefficients
      of variation of the coagulations were compared among the three groups. RESULTS:
      The minimum transverse diameters of the RF-induced coagulations in groups B (3.5
      cm+/-0.5) and C (3.8 cm+/-0.6) were significantly larger than that in group A
      (2.6 cm+/-0.3). The mean coagulation volumes produced in the multipolar group
      (25.1 cm3+/-5.2) were greater than those produced in the monopolar groups (11.6
      cm3+/-3.7 and 18.1 cm3+/-5.8) (P<.05). The mean ratio of transverse diameter to
      vertical diameter of the coagulations was larger in groups B and C (1.2+/-0.2 and
      1.0+/-0.1, respectively) than in group A (0.8+/-0.2) (P<.05). In addition, the
      coefficients of variation for groups A, B, and C were 0.33, 0.30, and 0.21,
      respectively. The procedure time was longer with the multipolar technique (27.2
      minutes+/-4.9) than with the monopolar technique with a single or cluster probe
      (12 minutes). CONCLUSIONS: Multipolar RF ablation showed at least equivalent or
      better in vivo efficiency for creating a larger coagulation than monopolar RF
      ablation with single or cluster electrodes, but with a longer procedure time and
      at slightly greater complexity.

PMID- 18057292
TI  - CT-guided instillation of 5% dextrose in water into the anterior pararenal space
      before renal radiofrequency ablation in a porcine model: positive and negative
      effects.
AB  - PURPOSE: To assess the positive and negative effects of computed tomographic (CT)
      guided instillation of 5% dextrose in water (D5W) into the anterior pararenal
      space before renal radiofrequency (RF) ablation in a porcine model. MATERIALS AND
      METHODS: Under CT guidance, D5W was instilled into the right anterior pararenal
      space of 10 pigs and RF ablation performed in the right kidney. For the control
      lesions, RF ablation was performed in the left kidney of the same pigs without
      pretreatment with D5W. Approximately 1 week after RF ablation, bowel adhesion to
      both kidneys was compared by using a 5-point scale at open laparotomy, as
      follows: grade 0=no adhesion, grade 1=detachable adhesion, grade 2=grade 1
      adhesion plus other adhesion to organs, grade 3=undetachable adhesion, and grade
      4=bowel perforation. The areas of coagulation necrosis in both kidneys were
      compared at pathologic examination. RESULTS: Bowel adhesions to the right kidneys
      were classified as grade 0 in nine pigs and as grade 1 in one pig, whereas those
      to the left kidneys were classified as grade 2 in two pigs and as grade 3 in
      eight (P<.05). The mean areas of coagulation necrosis in right and left kidneys
      were 0.58 cm2+/-0.5 and 1.53 cm2+/-1.3, respectively (P<.05). CONCLUSIONS: CT
      guided D5W instillation has a positive effect in reducing the amount of bowel
      adhesion injury during RF ablation. However, this technique may limit the area of
      coagulation necrosis in a swine model. Longer term pathologic evaluation is
      necessary to fully understand the effects of D5W instillation.

PMID- 18057293
TI  - Percutaneous transsplenic access in the management of bleeding varices from
      chronic portal vein thrombosis.
AB  - Three patients with life-threatening variceal hemorrhage secondary to portal vein
      (PV) thrombosis underwent endovascular treatment via the transsplenic route. The
      indications, techniques, and early outcomes are described. Each patient had
      successful portal/splenic vein recanalization with or without transjugular
      intrahepatic portosystemic shunt (TIPS) creation and variceal embolization with
      conventional catheter and wire techniques. The transsplenic approach is a useful
      addition to the interventional armamentarium that can be used in cases refractory
      to endoscopic management and unsuitable for surgical shunt procedures or
      conventional TIPS procedures. Longer-term follow-up will be needed to establish
      the durability of these procedures.

PMID- 18057294
TI  - Pulmonary arterial coil embolization for the management of persistent type I
      hepatopulmonary syndrome after liver transplantation.
AB  - Hepatopulmonary syndrome (HPS) is a common complication of chronic liver disease.
      The definitive therapy is liver transplantation. Medical management, transjugular
      intrahepatic portosystemic shunt creation, and pulmonary arterial coil
      embolization have been described as temporizing measures until liver
      transplantation is performed. In earlier studies, the degree of right-to-left
      shunting in HPS has been shown to be an indicator of posttransplantation
      morbidity and mortality. The present article describes a case of type I HPS
      managed by liver transplantation and augmented by posttransplantation pulmonary
      arterial coil embolization to reduce the patient's posttransplantation morbidity.

PMID- 18057295
TI  - Migration of the Gunther Tulip inferior vena cava filter to the chest.
AB  - The authors describe two cases in which Gunther Tulip inferior vena cava filters
      migrated to the chest, necessitating open-heart surgery for retrieval. In the
      first case, a 52-year-old man was transferred to their hospital from an outside
      facility after the filter migrated to the main pulmonary artery during attempted
      filter placement. In the second case, a 72-year-old man, a Gunther Tulip filter
      was found to have migrated to the tricuspid valve after cardiopulmonary arrest
      and subsequent resuscitation, including emergent central venous line placement.
      The authors present the relevant details of both cases, discuss possible
      preventive strategies, and review the available literature about migration of the
      Gunther Tulip filter.

PMID- 18057296
TI  - Percutaneous embolization of a left-sided varicocele in a patient with a
      duplicated inferior vena cava.
AB  - Anatomic variants of the inferior vena cava (IVC) can make selective
      catheterization of the spermatic vein difficult. In an attempt to embolize the
      left varicocele, the authors identified a duplicated IVC on an initial venogram
      through the right common femoral vein. However, it was not possible to cannulate
      the left spermatic vein with this conventional approach, necessitating an
      approach from the right internal jugular vein. The left varicocele was
      successfully embolized.

PMID- 18057297
TI  - Hepatic yttrium-90 radioembolotherapy in metastatic colorectal cancer treated
      with cetuximab or bevacizumab.
AB  - Yttrium-90 microspheres have been recently approved by the Food and Drug
      Administration and have become available to physicians in the United States for
      the treatment of hepatic neoplasia. Published results regarding the benefits of
      90Y radioembolotherapy within the rapidly evolving landscape of systemic
      therapies for advanced unresectable colorectal cancer are limited. In that
      context, outcomes in patients who have received the recently approved biologic
      agents bevacizumab and cetuximab in addition to chemotherapy are unknown. This
      report briefly describes the authors' treatment experience with this cohort of
      patients.

PMID- 18057298
TI  - Air embolism during needle placement for CT-guided radiofrequency ablation of an
      unresectable metastatic lung lesion.
AB  - Percutaneous computed tomographic (CT)-guided radiofrequency (RF) ablation is a
      minimally invasive and promising procedure for unresectable lung tumors. In
      general, the procedure is safe and its complications are minor. A few cases of
      serious complications, however, have been reported. The authors report on a case
      of air embolism during electrode insertion into a metastatic lung tumor. The
      patient became unresponsive; however, he recovered 10 minutes later and the air
      embolism disappeared spontaneously. Although air embolism during RF ablation of a
      lung tumor is a rare complication, radiologists performing the percutaneous
      procedure should be aware of this complication and be familiar with the
      appropriate management.

PMID- 18057299
TI  - Implantation of a port-catheter system through the superior mesenteric artery for
      repeated hepatic arterial infusion chemotherapy.
AB  - Between March 1999 and March 2006, 292 patients at the authors' institution
      required placement of a percutaneously implantable port-catheter system through
      which repeated hepatic arterial infusion chemotherapy would be administered. In
      10 patients, the port-catheter system was implanted through the superior
      mesenteric artery. In these patients, implantation through the superior
      mesenteric artery instead of the celiac artery was necessary because all hepatic
      arteries arose from the superior mesenteric artery or because the blood supply to
      almost all tumors was from a hepatic artery arising from the superior mesenteric
      artery. Implantation of the port-catheter system was successful without
      complications in these 10 patients.

PMID- 18057300
TI  - Pulmonary hemorrhage secondary to aortobronchial fistula occurring soon after the
      placement of an endovascular stent for a thoracic aortic aneurysm.

PMID- 18057301
TI  - Abnormally superior course of the right subclavian artery.

PMID- 18057302
TI  - The troublesome filter.

PMID- 18057303
TI  - The first biosimilar epoetin: but how similar is it?

PMID- 18057304
TI  - On the importance of pedal edema in hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Volume control is a key component of treatment of
      hemodialysis patients. The role of pedal edema as a marker of volume is unknown.
      The objective of this study was to determine factors that are associated with
      edema. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cross-sectional study of
      asymptomatic hemodialysis patients (n = 146) in four university-affiliated
      hemodialysis units was conducted. Echocardiographic variables, blood volume
      monitoring, plasma volume markers (plasma renin and aldosterone and N-terminal
      pro B-type natriuretic peptide), and inflammation markers (C-reactive protein and
      IL-6) were measured as exposures, and edema was measured as outcome. RESULTS: In
      a multivariate logistic regression analysis, age, body mass index, and left
      ventricular hypertrophy were independent determinants of edema. Compared with
      patients with normal or low weight, overweight patients had odds ratio for edema
      of 5.7 (95% confidence interval [CI] 1.0 to 31.8), and obese patients of 44.8
      (95% CI 9.0 to 223). Patients in the top quartile of left ventricular mass index
      and normal to low weight had odds ratio of edema of 7.7 (95% CI 2.3 -25.9), those
      who were overweight of 43.5 (95% CI 3.9 to 479.8), and those who were obese of
      344.8 (95% CI 33.8 to 3515). Inferior vena cava diameter, blood volume
      monitoring, plasma volume markers, and inflammation markers were not determinants
      of edema. CONCLUSIONS: Pedal edema correlates with cardiovascular risk factors
      such as age, body mass index, and left ventricular mass but does not reflect
      volume in hemodialysis patients.

PMID- 18057306
TI  - Sodium bicarbonate is associated with an increased incidence of contrast
      nephropathy: a retrospective cohort study of 7977 patients at mayo clinic.
AB  - BACKGROUND AND OBJECTIVES: The role of sodium bicarbonate in preventing contrast
      nephropathy needs to be evaluated in clinical settings. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study at Mayo
      Clinic in Rochester, Minnesota, to assess the risk of contrast nephropathy
      associated with the use of sodium bicarbonate, N-acetylcysteine, and the
      combination of sodium bicarbonate with N-acetylcysteine from April 2004 to May
      2005. Contrast nephropathy was defined as postexposure creatinine elevation of >
      or =25% or >0.5 mg/dl within 7 d of contrast exposure. RESULTS: A total of 11,516
      contrast exposures in 7977 patients had creatinine values available for review
      before and after contrast exposure. More than 90% of exposures to agents
      prophylactic for contrast nephropathy were available for analysis. Sodium
      bicarbonate was used in 268 cases, N-acetylcysteine was used in 616 cases, and
      both agents were used in combination in 221 cases of contrast exposure. After
      adjustment for total volume of hydration, medications, age, gender, prior
      creatinine, contrast iodine load, prior exposure to contrast material, type of
      imaging study, heart failure, hypertension, renal failure, multiple myeloma, and
      diabetes mellitus, use of sodium bicarbonate alone was associated with an
      increased risk of contrast nephropathy compared with no treatment (odds ratio
      3.10, 95% confidence interval 2.28 to 4.18; P < 0.001). N-acetylcysteine alone
      and in combination with sodium bicarbonate was not associated with any
      significant difference in the incidence of contrast nephropathy. CONCLUSIONS: The
      use of intravenous sodium bicarbonate was associated with increased incidence of
      contrast nephropathy. Use of sodium bicarbonate to prevent contrast nephropathy
      should be evaluated further rather than adopted into clinical practice.

PMID- 18057305
TI  - Lipoprotein abnormalities associated with mild impairment of kidney function in
      the multi-ethnic study of atherosclerosis.
AB  - BACKGROUND AND OBJECTIVES: Impaired kidney function is associated with increased
      risk for cardiovascular disease and may progress over time to end-stage renal
      disease. Abnormal lipoprotein metabolism has been implicated as a possible cause
      of these complications, but lipoproteins have not been described at the earliest
      stages of kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This
      study examined cross-sectional associations of serum cystatin C with conventional
      lipid measurements and detailed nuclear magnetic resonance lipoprotein
      measurements in the community-based Multi-Ethnic Study of Atherosclerosis. A
      total of 5109 participants with estimated glomerular filtration rate > or =60
      ml/min per 1.73 m(2) were included in analyses. RESULTS: Adjusting for age,
      gender, race/ethnicity, diabetes, impaired fasting glucose, BP, smoking,
      medications, body mass index, and albuminuria, greater cystatin C concentrations
      were associated with progressively unfavorable lipid and lipoprotein
      concentrations, including greater triglyceride concentration (+22 mg/dl,
      comparing fifth versus first quintiles of cystatin C) and lesser high-density
      lipoprotein cholesterol concentration (-7 mg/dl) but not with low-density
      lipoprotein cholesterol measured using conventional methods. When low-density
      lipoprotein particle subclasses were examined in more detail using nuclear
      magnetic resonance, greater cystatin C was associated with greater concentrations
      of atherogenic small low-density lipoprotein particles (+63 nmol/L) and
      intermediate-density lipoprotein particles (+6 nmol/L) and with a decrease in
      mean low-density lipoprotein particle size. CONCLUSIONS: Lipoprotein
      abnormalities are present with milder degrees of renal impairment than previously
      recognized, and abnormalities in low-density lipoprotein particle distribution
      may not be appreciated using conventional lipid measurements. These abnormalities
      may contribute to kidney disease progression and/or cardiovascular disease.

PMID- 18057307
TI  - Short-term treatment with sevelamer increases serum fetuin-a concentration and
      improves endothelial dysfunction in chronic kidney disease stage 4 patients.
AB  - BACKGROUND AND OBJECTIVES: Vascular calcification and endothelial dysfunction
      contribute to the development of cardiovascular disease in patients with chronic
      kidney disease (CKD). Sevelamer, a non-calcium-based phosphate binder, has been
      shown to attenuate cardiovascular calcification in CKD patients, although the
      exact mechanism has not been clarified. This study was designed to investigate
      the effect of short-term sevelamer treatment on both serum fetuin-A
      concentrations and endothelial dysfunction seen in CKD patients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Fifty nondiabetic stage 4 CKD patients whose
      phosphate levels were > or =5.5 mg/dl were enrolled in this 8-wk randomized
      prospective study. Thirty-six healthy volunteers served as matched controls.
      Patients were treated with either sevelamer (n = 25, 12 males) or calcium acetate
      (n = 25, 13 males). Fetuin-A, high-sensitivity C-reactive protein, Ca x PO4
      product, flow-mediated dilation (FMD), insulin, and homeostasis model assessment
      (HOMA) were obtained at baseline and after the treatment period. RESULTS: As
      expected, CKD patients had significantly lower levels of fetuin-A and FMD, and
      significantly higher levels of intact parathyroid hormone, Ca x PO4 product, and
      high-sensitivity C-reactive protein than controls (P < 0.001 for all). The use of
      sevelamer led to a significant increase in the fetuin-A concentration with
      improvement in FMD, whereas no significant difference was observed in the calcium
      acetate group. In a multiple regression analysis, FMD levels were independently
      related to fetuin-A both before (beta = 0.63, P < 0.001) and after (beta = 0.38,
      P = 0.004) treatment. CONCLUSIONS: This small, randomized, prospective study
      shows that short-term sevelamer treatment significantly increases fetuin-A levels
      and improves FMD in nondiabetic stage 4 CKD patients.

PMID- 18057308
TI  - Renal parenchymal hypoxia, hypoxia adaptation, and the pathogenesis of
      radiocontrast nephropathy.
AB  - BACKGROUND AND OBJECTIVES: Renal parenchymal Po(2) declines after the
      administration of iodinated radiocontrast agents, reaching critically low levels
      of approximately 10 mmHg in medullary structures. DESIGN, SETTING, PARTICIPANTS,
      & MEASUREMENTS: In this review, the causes of renal parenchymal hypoxia and its
      potential role in the pathogenesis of contrast nephropathy are appraised.
      RESULTS: Commonly associated predisposing factors are associated with a
      propensity to enhance renal hypoxia. Indeed, animal models of radiocontrast
      nephropathy require the induction of such predisposing factors, mimicking
      clinical scenarios that lead to contrast nephropathy in high-risk individuals. In
      these models, in association with medullary hypoxic damage, a transient local
      cellular hypoxia response is noted, initiated at least in part by hypoxia
      inducible factors. Some predisposing conditions that are distinguished by
      chronically aggravated medullary hypoxia, such as tubulointerstitial disease and
      diabetes, are characterized by a priori upregulation of hypoxia-inducible
      factors, which seems to confer tolerance against radiocontrast-related hypoxic
      tubular damage. Renal dysfunction under such circumstances likely reflects to
      some extent altered intrarenal hemodynamics, rather than acute tubular injury.
      CONCLUSIONS: Real-time, noninvasive novel methods may help to differentiate
      between evolving tubular damage and altered hemodynamics and in the design of
      appropriate preventive interventions.

PMID- 18057309
TI  - Association between serum 2-microglobulin level and infectious mortality in
      hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Secondary analysis of the Hemodialysis Study showed
      that serum beta(2)-microglobulin levels predicted all-cause mortality and that
      high-flux dialysis was associated with decreased cardiac deaths in hemodialysis
      patients. This study examined the association of serum beta(2)-microglobulin
      levels and dialyzer beta(2)-microglobulin kinetics with the two most common
      causes of deaths: Cardiac and infectious diseases. Cox regression analyses were
      performed to relate cardiac or infectious deaths to cumulative mean follow-up
      predialysis serum beta(2)-microglobulin levels while controlling for baseline
      demographics, comorbidity, residual kidney function, and dialysis-related
      variables. RESULTS: The cohort of 1813 patients experienced 180 infectious deaths
      and 315 cardiac deaths. The adjusted hazard ratio for infectious death was 1.21
      (95% confidence interval 1.07 to 1.37) per 10-mg/L increase in beta(2)
      microglobulin. This association was independent of the prestudy years on
      dialysis. In contrast, the association between serum beta(2)-microglobulin level
      and cardiac death was not statistically significant. In similar regression
      models, higher cumulative mean Kt/V of beta(2)-microglobulin was not
      significantly associated with either infectious or cardiac mortality in the full
      cohort but exhibited trends suggesting an association with lower infectious
      mortality (relative risk 0.93; 95% confidence interval 0.86 to 1.01, for each 0.1
      U increase in beta(2)-microglobulin Kt/V) and lower cardiac mortality (relative
      risk 0.93; 95% confidence interval 0.87 to 1.00) in the subgroup with >3.7
      prestudy years of dialysis. CONCLUSIONS: These results generally support the
      notion that middle molecules are associated with systemic toxicity and that their
      accumulation predisposes dialysis patients to infectious deaths, independent of
      the duration of maintenance dialysis.

PMID- 18057310
TI  - Bone and mineral guidelines for patients with chronic kidney disease: a call for
      revision.
AB  - Recent clinical studies of mineral metabolism in patients with chronic kidney
      disease have helped to verify and extend the Kidney Disease Outcomes Quality
      Initiative practice guidelines for bone metabolism and disease that were
      published in 2003. In particular, investigations that examined calcium loading,
      vitamin D therapy, and mortality risk associated with serum calcium and phosphate
      in dialysis patients have been the most helpful clinically. As a consequence,
      there is now a growing interest to have the previous guidelines amended
      accordingly, which will be performed through the Kidney Disease: Improving Global
      Outcomes working group after a debate within the nephrology community. The new
      data support this call for revision in an attempt to improve survival of the
      dialysis patient by emphasizing the importance of intravenous vitamin D therapy
      and of preventing excess calcium loading. These studies also suggest avenues for
      future investigation into nontraditional causes and treatments of cardiovascular
      disease in patients with chronic kidney disease.

PMID- 18057311
TI  - Comparative analysis of meiotic progression in female mice bearing mutations in
      genes of the DNA mismatch repair pathway.
AB  - The DNA mismatch repair (MMR) family functions in a variety of contexts to
      preserve genome integrity in most eukaryotes. In particular, members of the MMR
      family are involved in the process of meiotic recombination in germ cells. MMR
      gene mutations in mice result in meiotic disruption during prophase I, but the
      extent of this disruption often differs between male and female meiocytes. To
      address the role of MMR proteins specifically in female meiosis, we explored the
      progression of oocytes through prophase I and the meiotic divisions in mice
      harboring deletions in members of the MMR pathway (Mlh1, Mlh3, Exo1, and an
      ATPase-deficient variant of Mlh1, Mlh1(G67R)). The colocalization of MLH1 and
      MLH3, key proteins involved in stabilization of nascent crossovers, was dependent
      on intact heterodimer formation and was highly correlated with the ability of
      oocytes to progress through to metaphase II. The exception was Exo1(-/-) oocytes,
      in which normal MLH1/MLH3 localization was observed followed by failure to
      proceed to metaphase II. All mutant oocytes were able to resume meiosis after
      dictyate arrest, but they showed a dramatic decline in chiasmata (to less than
      25% of normal), accompanied by varied progression through metaphase I. Taken
      together, these results demonstrate that MMR function is required for the
      formation and stabilization of crossovers in mammalian oocytes and that, in the
      absence of a functional MMR system, the failure to maintain chiasmata results in
      a reduced ability to proceed normally through the first and second meiotic
      divisions, despite near-normal levels of meiotic resumption after dictyate
      arrest.

PMID- 18057312
TI  - Epithelial cells remove apoptotic epithelial cells during post-lactation
      involution of the mouse mammary gland.
AB  - Following the cessation of lactation, the mammary gland undergoes a physiologic
      process of tissue remodeling called involution in which glandular structures are
      lost, leaving an adipose tissue compartment that takes up a much larger
      proportion of the tissue. A quantitative morphometric analysis was undertaken to
      determine the mechanisms for clearance of the epithelial cells during this
      process. The involution process was set in motion by removal of pups from 14-day
      lactating C57BL/6 mice. Within hours, milk-secreting epithelial cells were shed
      into the glandular lumen. These cells became apoptotic, exhibiting exposure of
      phosphatidylserine residues on their surfaces, activation of effector caspase-3,
      staining for caspase-cleaved keratin 18, loss of internal organellar structure,
      and nuclear breakdown, but minimal blebbing or generation of apoptotic bodies.
      Clearance of residual milk and the shed epithelial cells was rapid, with most of
      the removal occurring in the first 72 h. Intact apoptotic epithelial cells were
      engulfed in large numbers by residual viable epithelial cells into spacious
      efferosomes. This process led to essentially complete involution within 4 days,
      at which point estrous cycling recommenced. Macrophages and other inflammatory
      cells did not contribute to the clearance of either residual milk or apoptotic
      cells, which appeared to be due entirely to the epithelium itself.

PMID- 18057313
TI  - Regulation of murine lactate dehydrogenase C (Ldhc) gene expression.
AB  - Expression of Ldhc begins with the onset of meiosis in male germ cells and
      continues throughout spermatogenesis. Transcriptional regulatory mechanisms,
      especially in primary spermatocytes, are poorly described because of the lack of
      a reliable cell culture system. We constructed mouse transgenics and transfected
      germ cells in situ to study expression of the testis-specific isozyme of lactate
      dehydrogenase (LDH). From previous work, we determined that a 100-bp Ldhc core
      promoter contained potential cis regulatory elements, including a palindrome (-21
      to +10), GC box (-70 to -65), and cAMP-responsive element (CRE) sites (-53 to 
      49, -39 to -35). We provide here the demonstration of a functional role for these
      sequences by expression of mutated transgenes in vivo. Our results reveal for the
      first time that mutation of the GC box does not abolish promoter activity, which
      remains testis-specific. Mutation of GC box or CRE sites resulted in a 73% and
      74% reduction in promoter activity, respectively, in a transient transfection of
      germ cells in vivo by electroporation; the combination of GC box and CRE site
      mutations eliminates promoter activity. Therefore, we conclude that simultaneous
      occupancy of the GC box and CRE sites in the core promoter is necessary for full
      expression of Ldhc in the testis.

PMID- 18057314
TI  - Interleukin 1 alpha (IL1A) is a novel regulator of the blood-testis barrier in
      the rat.
AB  - Throughout spermatogenesis, leptotene spermatocytes must traverse the blood
      testis barrier (BTB) at stages VIII-XI to gain entry into the adluminal
      compartment for continued development. However, the mechanism underlying BTB
      restructuring remains somewhat elusive. In this study, interleukin 1 alpha (IL1A)
      was administered intratesticularly to adult rats in order to assess its effects
      on spermatogenesis. IL1A was shown to perturb Sertoli-germ cell adhesion,
      resulting in germ cell loss from approximately 50% of seminiferous tubules by 15
      days posttreatment. Equally important, the functional integrity of the BTB was
      compromised when inulin-fluorescein isothiocyanate was detected in the adluminal
      compartment of the seminiferous epithelium following its administration via the
      jugular vein. Interestingly, IL1A did not affect the steady-state levels of
      proteins that confer BTB function, namely OCLN, CLDN1, F11R, TJP1, and CDH2.
      Instead, the localizations of OCLN, F11R, and TJP1 in the seminiferous epithelium
      were altered; these proteins appeared to move away from sites of cell-cell
      contact. Moreover, IL1A was shown to perturb the orderly arrangement of
      filamentous actin at the BTB and apical ectoplasmic specialization with distinct
      areas illustrating loss of actin filaments. Taken collectively, these results
      suggest that IL1A-induced BTB disruption is not mediated via the reduction of
      target protein levels. Instead, IL1A's primary cellular target appears to be the
      Sertoli cell actin cytoskeleton. It is possible that localized production of IL1A
      by Sertoli and/or germ cells in vivo results in BTB restructuring, and this may
      facilitate the movement of leptotene spermatocytes across the BTB.

PMID- 18057315
TI  - Selective saccadic palsy after cardiac surgery.

PMID- 18057316
TI  - Applicability of NINDS-sponsored studies to community-based physician
      involvement.
AB  - BACKGROUND: The National Institute of Neurological Disorders and Stroke (NINDS)
      Clinical Trials Group established the Clinical Research Collaboration (CRC)
      Project in 2005 to increase community-based physician involvement in NINDS
      sponsored research. METHODS: We assessed a random sample of 112 of the more than
      1,000 current NINDS-sponsored clinical research studies to determine which could
      involve community physicians in enrollment or follow-up. Scoring factors were
      based on the premise that participation is feasible for noninvasive studies with
      simple screening, and follow-up criteria and visit frequency consistent with
      usual care. Scored studies included 26 Phase III, 31 Phase I/II, and 55
      nonclinical trials. RESULTS: Overall, 41% of the sampled research studies were
      considered conducive to community physician participation that exceeds referral
      only; 21% with participation in all study activities and 20% with ability to
      provide some follow-up. Specialized neuropsychological or neurologic scale
      testing was judged to exclude community physician participation in 16% of
      studies. CONCLUSION: Many National Institute of Neurological Disorders and Stroke
      studies are available in which community-based physicians could participate.
      Involving community physicians may increase efficiency of completing clinical
      research and encourage application of research findings in community practices.

PMID- 18057317
TI  - Somatic mutations in GLI3 can cause hypothalamic hamartoma and gelastic seizures.

PMID- 18057318
TI  - HLA-DRB1 and multiple sclerosis in Malta.
AB  - BACKGROUND: By comparison with the neighboring island of Sicily, the frequency of
      multiple sclerosis (MS) in Malta is remarkably low. METHODS: To explore whether
      the relative rarity of MS in Malta might be the result of lower population
      frequencies of major histocompatibility complex susceptibility alleles, we
      genotyped the HLA-DRB1 locus in 77 Maltese-born patients (97% of the prevalent
      unrelated native cases) and 206 Maltese controls. We made comparisons with
      previously published data for Sicily and other European countries. RESULTS: The
      anticipated association with HLA-DRB1*15, the main susceptibility allele in most
      other populations, was confirmed (p(c) = 0.009) but, in addition, we also
      observed an equally strong, and apparently protective, effect of the HLA-DRB1*11
      allele (p(c) = 0.016). In comparison with previously published data from Sicily,
      we found that all HLA-DRB1 risk alleles were more common in Malta, whereas HLA
      DRB1*11 was slightly less common. CONCLUSIONS: The difference in prevalence seen
      between the neighboring islands of Malta and Sicily cannot be explained by
      differences in background HLA-DRB1 population allele frequencies, which if
      anything would predict a higher rate of disease in Malta than in Sicily.

PMID- 18057319
TI  - Progressive bone deficit in epilepsy.
AB  - OBJECTIVE: Chronic treatment with antiepileptic medication is associated with
      reduced bone mineral density (BMD), which may underlie the two- to sixfold
      increase in fracture rates observed in patients with epilepsy. The objective was
      to determine the timing of the BMD deficit in ambulatory children with epilepsy.
      METHODS: A cross-sectional evaluation was conducted in 82 ambulatory children
      aged 6 to 18 years (12.4 +/- 3.3 years) with epilepsy for <1 year (n = 18), 1 to
      5 years (n = 37), and 6 or more years (n = 27). Controls were 32 healthy children
      aged 12.8 +/- 2.6 years. Age- and sex-corrected total body BMD Z-score was
      measured. RESULTS: Total BMD Z-score was lower in children with epilepsy (0.10 +/
      0.96; CI = -0.08, 0.34) compared to controls (0.57 +/- 0.74; CI = 0.3, 0.84; p =
      0.03). Increasing duration of epilepsy was associated with a progressive
      reduction in BMD compared to controls (Spearman r = -0.197; p = 0.03). Compared
      to controls, those with epilepsy for 1 to 5 years had a mean BMD Z-score of 0.13
      +/- 0.78 (CI = -0.13, 0.39; p = 0.04) and in those treated for 6 or more years
      BMD was 0.06 +/- 1.11 (CI = -0.38, 0.5; p = 0.04). For those with epilepsy for <1
      year BMD was 0.23 +/- 1.1 (CI = -0.31, 0.77; p = 0.21). CONCLUSIONS: Children
      treated for epilepsy sustain significant bone mineral density (BMD) deficit
      compared to controls during the initial 1 to 5 years of treatment which
      progressively worsens thereafter. This progressive BMD deficit may be a
      contributing factor to the increased fracture risk observed in patients with
      epilepsy and may accelerate aging-related osteoporosis.

PMID- 18057320
TI  - FMR1 CGG repeat length predicts motor dysfunction in premutation carriers.
AB  - BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently
      described, underrecognized neurodegenerative disorder of aging fragile X mental
      retardation 1 (FMR1) premutation carriers, particularly men. Core motor features
      are action tremor, gait ataxia, and parkinsonism. Carriers have expanded CGG
      repeats (55 to 200); larger expansions cause fragile X syndrome, the most common
      heritable cause of mental retardation and autism. This study determines whether
      CGG repeat length correlates with severity and type of motor dysfunction in
      premutation carriers. METHODS: Persons aged >or=50 years with a family history of
      fragile X syndrome underwent structured videotaping. Movement disorder
      neurologists, blinded to carrier status, scored the tapes using modified
      standardized rating scales. CGG repeat length analyses for women incorporated the
      activation ratio, which measures the percentage of normal active chromosome X
      alleles. RESULTS: Male carriers (n = 54) had significantly worse total motor
      scores, especially in tremor and ataxia, than age-matched male noncarriers (n =
      51). There was a trend toward a difference between women carriers (n = 82) and
      noncarriers (n = 39). In men, increasing CGG repeat correlated with greater
      impairment in all motor signs. In women, when activation ratio was considered,
      increasing CGG correlated with greater ataxia. CONCLUSIONS: CGG repeat size is
      significantly associated with overall motor impairment in premutation carriers.
      Whereas this association is most pronounced for men and covers overall motor
      impairment-tremor, ataxia, and parkinsonism-the association exists for ataxia
      among women carriers. This is the first report of a significant correlation
      between the premutation status and a motor feature of fragile X-associated
      tremor/ataxia syndrome in women.

PMID- 18057321
TI  - The dorsomedial hypothalamic nucleus is not necessary for the expression of
      circadian food-anticipatory activity in rats.
AB  - Restricted daytime feeding generates food-anticipatory activity (FAA) by
      entrainment of a circadian pacemaker separate from the light-entrainable
      pacemaker located in the SCN. The dorsomedial hypothalamic nucleus (DMH) has been
      proposed as the site of food-entrainable oscillators critical for the expression
      of FAA, but another study found no effects of complete DMH ablation on FAA. To
      account for these different results, the authors examined methodological factors,
      including (1) cage configuration and feeding method and (2) use of social cues.
      Intact and DMH-ablated rats were maintained on one 4-h daily meal in the middle
      of the light period, using caging and feeding methods matching those of Gooley et
      al. (2006). Rats with partial or complete DMH ablation were less nocturnal during
      ad lib food access but exhibited normal FAA during restricted feeding, as
      quantified by FAA magnitude, ratios, latency to appearance, duration, and
      precision. To evaluate the use of social cues, intact rats naive to restricted
      feeding schedules were food deprived for 72 h on 4 tests. Daytime activity
      increased during food deprivation, but the magnitude and waveform of this
      activity was not influenced by the presence of food-entrained rats exhibiting
      robust FAA in adjacent cages. Thus, hungry intact rats do not use social cues to
      anticipate a daily mealtime, suggesting that DMH-ablated rats do not anticipate
      meals by reacting to sounds from food-entrained intact rats in adjacent cabinets.
      These results confirm our previous finding that the DMH is not critical for
      normal expression of FAA in rats, and this observation is extended to food
      restriction methodologies used by other labs. The methodological differences that
      do underlie discrepant results remain unresolved, as does the location of food
      entrainable oscillators, input pathways, and output pathways critical for FAA.

PMID- 18057322
TI  - Is food-directed behavior an appropriate measure of circadian entrainment to
      restricted daytime feeding?

PMID- 18057323
TI  - Food entrainment: methodological issues.

PMID- 18057324
TI  - Cis-combination of the classic per(S) and per(L) mutations results in arrhythmic
      Drosophila with ectopic accumulation of hyperphosphorylated PERIOD protein.
AB  - The 1st circadian "clock" gene identified was the X-linked period (per) gene in
      Drosophila melanogaster. In the pioneering initial report, Konopka and Benzer
      (1971) characterized 3 alleles of per that shortened (per (S); approximately 19
      h), lengthened (per (L); approximately 29 h), or abolished (per (0)) circadian
      behavioral rhythms. They also showed that transheterozygotes carrying the per (S)
      and per (L) mutations exhibit robust behavioral rhythms with nearly normal
      periods of approximately 23 h, highlighting the semidominant nature of many clock
      mutants. In this study, per (0) flies bearing a doubly mutated per transgene that
      carries both the per (S) and per (L) alleles (per (0); per (S/L)) were analyzed
      for behavioral and molecular rhythms. Unlike singly mutated versions, the per
      (0);per ( S/L) transgenic flies are arrhythmic in constant dark conditions and
      exhibit little, if any, entrainment to daily light-dark cycles. In a wildtype per
      (+) background, expression of per ( S/L) abolishes behavioral rhythms, indicating
      that it functions in a transdominant negative fashion. Biochemical analysis of
      head extracts revealed that only hyperphosphorylated isoforms of the PERS/L
      protein are detected throughout a daily cycle, and the levels remain constant.
      Intriguingly, little if any PERS/L is observed in key pacemaker neurons that
      control daily activity rhythms, consistent with the notion that
      hyperphosphorylated isoforms of PER are unstable. Nonetheless, PERS/L is detected
      in ectopic cells in the brain, in which it exhibits an unusual localization,
      mainly staining the periphery of the nucleus. These results suggest that
      posttranslational mechanisms play a key role in limiting the accumulation of PER
      to specific cells. On a broader scope, our results indicate that the semidominant
      effects of period-altering alleles observed in trans are not necessarily
      preserved in the cis-configuration and that novel phenotypes can emerge.

PMID- 18057325
TI  - An antennal circadian clock and circadian rhythms in peripheral pheromone
      reception in the moth Spodoptera littoralis.
AB  - Circadian rhythms are observed in mating behaviors in moths: females emit sex
      pheromones and males are attracted by these pheromones in rhythmic fashions. In
      the moth Spodoptera littoralis, we demonstrated the occurrence of a circadian
      oscillator in the antenna, the peripheral olfactory organ. We identified
      different clock genes, period (per), cryptochrome1 (cry1) and cryptochrome2
      (cry2), in this organ. Using quantitative real-time PCR (qPCR), we found that
      their corresponding transcripts cycled circadianly in the antenna as well as in
      the brain. Electroantennogram (EAG) recordings over 24 h demonstrated for the
      first time a circadian rhythm in antennal responses of a moth to sex pheromone.
      qPCR showed that out of one pheromone-binding protein (PBP), one olfactory
      receptor (OR), and one odorant-degrading enzyme (ODE), all putatively involved in
      the pheromone reception, only the ODE transcript presented a circadian rhythm
      that may be related to rhythms in olfactory signal resolution. Peripheral or
      central circadian clock control of olfaction is then discussed in light of recent
      data.

PMID- 18057326
TI  - Interactions between dopamine and melatonin organize circadian rhythmicity in the
      retina of the green iguana.
AB  - Circadian physiology in the vertebrate retina is regulated by several
      neurotransmitters. In the lateral eyes of the green iguana the circadian rhythm
      of melatonin content peaks during the night while the rhythm of dopamine peaks
      during the day. In the present work, the authors explore the interaction of these
      2 neurotransmitters during the circadian cycle. They depleted retinal dopamine
      with intravitreal injections of 6-hydroxydopamine (6-OHDA) and measured ocular
      melatonin content in vivo throughout 1 circadian cycle. The circadian rhythm of
      ocular melatonin not only persisted but increased 10-fold in amplitude. This
      increase was substantially reduced by the intraocular administration of dopamine.
      6-OHDA-treated retinas, unlike those from untreated animals, did not express a
      circadian rhythm of melatonin synthesis in vitro. To deplete retinal melatonin,
      the authors pinealectomized iguanas and blocked retinal melatonin synthesis by
      depleting serotonin with intraocular injections of 5,6-dihydroxytryptamine. In
      animals so treated, they found that the circadian rhythm of retinal dopamine
      content was abolished, the levels of dopamine were lowered, and the levels of
      dopamine metabolites were greatly increased. The data suggest that in iguanas,
      the amplitude of the circadian rhythm of melatonin synthesis in the eye is
      suppressed by dopamine while the rhythm of dopamine depends, at least in part, on
      the presence of melatonin.

PMID- 18057327
TI  - Non-photic modulation of phase shifts to long light pulses.
AB  - Circadian rhythms can be reset by both photic and non-photic stimuli. Recent
      studies have used long light exposure to produce photic phase shifts or to
      enhance non-photic phase shifts. The presence or absence of light can also
      influence the expression of locomotor rhythms through masking; light during the
      night attenuates locomotor activity, while darkness during the day induces
      locomotor activity in nocturnal animals. Given this dual role of light, the
      current study was designed to examine the relative contributions of photic and
      non-photic components present in a long light pulse paradigm. Mice entrained to a
      light/dark cycle were exposed to light pulses of various durations (0, 3, 6, 9,
      or 12 h) starting at the time of lights-off. After the light exposure, animals
      were placed in DD and were either left undisturbed in their home cages or had
      their wheels locked for the remainder of the subjective night and subsequent
      subjective day. Light treatments of 6, 9, and 12 h produced large phase delays.
      These treatments were associated with decreased activity during the nocturnal
      light and increased activity during the initial hours of darkness following light
      exposure. When the wheels were locked to prevent high-amplitude activity, the
      resulting phase delays to the light were significantly attenuated, suggesting
      that the activity following the light exposure may have contributed to the
      overall phase shift. In a second experiment, telemetry probes were used to assess
      what effect permanently locking the wheels had on the phase shift to the long
      light pulses. These animals had phase shifts fully as large as animals without
      any form of wheel lock, suggesting that while non-photic events can modulate
      photic phase shifts, they do not play a role in the full phase-shift response
      observed in animals exposed to long light pulses. This paradigm will facilitate
      investigations into non-photic responses of the mouse circadian system.

PMID- 18057328
TI  - Exercise distributed across day and night does not alter circadian period in
      humans.
AB  - In rodents, increased activity due to running-wheel access is associated with a
      change in observed circadian period. In humans, exposure to exercise has failed
      to demonstrate similar effects on period. Methodological issues with prior
      studies such as light exposure during exercise, length of study, and method of
      measuring period confounded those evaluations of the effect of exercise on period
      in humans. In the present experiment, the authors examined the effect of exercise
      on period in 8 subjects using a 44-day within-subjects inpatient study. They used
      a 20-h forced desynchrony protocol, in which subjects were exposed to exercise
      across circadian phases under dim light conditions. Exercise consisted of three
      45-min sessions per wake period on an ergometer. Target exercise intensity was
      ~65% of maximal heart rate. Intrinsic circadian period was measured using both
      core body temperature and hourly plasma melatonin samples. Consistent with
      previous reports, the authors find no effect of exercise on endogenous circadian
      period as measured by either core body temperature or melatonin. Exercise
      distributed across biological day and night does not appear to affect circadian
      period.

PMID- 18057329
TI  - Computational analysis of mammalian cell division gated by a circadian clock:
      quantized cell cycles and cell size control.
AB  - Cell cycle and circadian rhythms are conserved from cyanobacteria to humans with
      robust cyclic features. Recently, molecular links between these two cyclic
      processes have been discovered. Core clock transcription factors, Bmal1 and Clock
      (Clk), directly regulate Wee1 kinase, which inhibits entry into the mitosis. We
      investigate the effect of this connection on the timing of mammalian cell cycle
      processes with computational modeling tools. We connect a minimal model of
      circadian rhythms, which consists of transcription-translation feedback loops,
      with a modified mammalian cell cycle model from Novak and Tyson (2004). As we
      vary the mass doubling time (MDT) of the cell cycle, stochastic simulations
      reveal quantized cell cycles when the activity of Wee1 is influenced by clock
      components. The quantized cell cycles disappear in the absence of coupling or
      when the strength of this link is reduced. More intriguingly, our simulations
      indicate that the circadian clock triggers critical size control in the mammalian
      cell cycle. A periodic brake on the cell cycle progress via Wee1 enforces size
      control when the MDT is quite different from the circadian period. No size
      control is observed in the absence of coupling. The issue of size control in the
      mammalian system is debatable, whereas it is well established in yeast. It is
      possible that the size control is more readily observed in cell lines that
      contain circadian rhythms, since not all cell types have a circadian clock. This
      would be analogous to an ultradian clock intertwined with quantized cell cycles
      (and possibly cell size control) in yeast. We present the first coupled model
      between the mammalian cell cycle and circadian rhythms that reveals quantized
      cell cycles and cell size control influenced by the clock.

PMID- 18057330
TI  - Green matters! Growing vegetation stimulates breeding under short-day conditions
      in wild canaries (Serinus canaria).

PMID- 18057331
TI  - Localization and diurnal expression of melanopsin, vertebrate ancient opsin, and
      pituitary adenylate cyclase-activating peptide mRNA in a teleost retina.

PMID- 18057332
TI  - Images in clinical medicine. Reversal of laryngeal paresis.

PMID- 18057333
TI  - Over the counter but no longer under the radar--pediatric cough and cold
      medications.

PMID- 18057334
TI  - Childhood obesity--the shape of things to come.

PMID- 18057335
TI  - Childhood body-mass index and the risk of coronary heart disease in adulthood.
AB  - BACKGROUND: The worldwide epidemic of childhood obesity is progressing at an
      alarming rate. Risk factors for coronary heart disease (CHD) are already
      identifiable in overweight children. The severity of the long-term effects of
      excess childhood weight on CHD, however, remains unknown. METHODS: We
      investigated the association between body-mass index (BMI) in childhood (7
      through 13 years of age) and CHD in adulthood (25 years of age or older), with
      and without adjustment for birth weight. The subjects were a cohort of 276,835
      Danish schoolchildren for whom measurements of height and weight were available.
      CHD events were ascertained by linkage to national registers. Cox regression
      analyses were performed. RESULTS: In 5,063,622 person-years of follow-up, 10,235
      men and 4318 women for whom childhood BMI data were available received a
      diagnosis of CHD or died of CHD as adults. The risk of any CHD event, a nonfatal
      event, and a fatal event among adults was positively associated with BMI at 7 to
      13 years of age for boys and 10 to 13 years of age for girls. The associations
      were linear for each age, and the risk increased across the entire BMI
      distribution. Furthermore, the risk increased as the age of the child increased.
      Adjustment for birth weight strengthened the results. CONCLUSIONS: Higher BMI
      during childhood is associated with an increased risk of CHD in adulthood. The
      associations are stronger in boys than in girls and increase with the age of the
      child in both sexes. Our findings suggest that as children are becoming heavier
      worldwide, greater numbers of them are at risk of having CHD in adulthood.

PMID- 18057336
TI  - Reduced exposure to PM10 and attenuated age-related decline in lung function.
AB  - BACKGROUND: Air pollution has been associated with impaired health, including
      reduced lung function in adults. Moving to cleaner areas has been shown to
      attenuate adverse effects of air pollution on lung function in children but not
      in adults. METHODS: We conducted a prospective study of 9651 adults (18 to 60
      years of age) randomly selected from population registries in 1990 and assessed
      in 1991, with 8047 participants reassessed in 2002. There was complete
      information on lung volumes and flows (e.g., forced vital capacity [FVC], forced
      expiratory volume in 1 second [FEV1], FEV1 as a percentage of FVC, and forced
      expiratory flow between 25 and 75% of the FVC [FEF25-75]), smoking habits, and
      spatially resolved concentrations of particulate matter that was less than 10
      microm in aerodynamic diameter (PM10) from a validated dispersion model assigned
      to residential addresses for 4742 participants at both the 1991 and the 2002
      assessments and in the intervening years. RESULTS: Overall exposure to individual
      home outdoor PM10 declined over the 11-year follow-up period (median, -5.3 mug
      per cubic meter; interquartile range, -7.5 to -4.2). In mixed-model regression
      analyses, with adjustment for confounders, PM10 concentrations at baseline, and
      clustering within areas, there were significant negative associations between the
      decrease in PM10 and the rate of decline in FEV1 (P=0.045), FEV1 as a percentage
      of FVC (P=0.02), and FEF25-75 (P=0.001). The net effect of a decline of 10 microg
      of PM10 per cubic meter over an 11-year period was to reduce the annual rate of
      decline in FEV1 by 9% and of FEF25-75 by 16%. Cumulative exposure in the interval
      between the two examinations showed similar associations. CONCLUSIONS: Decreasing
      exposure to airborne particulates appears to attenuate the decline in lung
      function related to exposure to PM10. The effects are greater in tests reflecting
      small-airway function.

PMID- 18057337
TI  - Respiratory effects of exposure to diesel traffic in persons with asthma.
AB  - BACKGROUND: Air pollution from road traffic is a serious health hazard, and
      people with preexisting respiratory disease may be at increased risk. We
      investigated the effects of short-term exposure to diesel traffic in people with
      asthma in an urban, roadside environment. METHODS: We recruited 60 adults with
      either mild or moderate asthma to participate in a randomized, crossover study.
      Each participant walked for 2 hours along a London street (Oxford Street) and, on
      a separate occasion, through a nearby park (Hyde Park). We performed detailed
      real-time exposure, physiological, and immunologic measurements. RESULTS:
      Participants had significantly higher exposures to fine particles (<2.5 microm in
      aerodynamic diameter), ultrafine particles, elemental carbon, and nitrogen
      dioxide on Oxford Street than in Hyde Park. Walking for 2 hours on Oxford Street
      induced asymptomatic but consistent reductions in the forced expiratory volume in
      1 second (FEV1) (up to 6.1%) and forced vital capacity (FVC) (up to 5.4%) that
      were significantly larger than the reductions in FEV1 and FVC after exposure in
      Hyde Park (P=0.04 and P=0.01, respectively, for the overall effect of exposure,
      and P<0.005 at some time points). The effects were greater in subjects with
      moderate asthma than in those with mild asthma. These changes were accompanied by
      increases in biomarkers of neutrophilic inflammation (sputum myeloperoxidase,
      4.24 ng per milliliter after exposure in Hyde Park vs. 24.5 ng per milliliter
      after exposure on Oxford Street; P=0.05) and airway acidification (maximum
      decrease in pH, 0.04% after exposure in Hyde Park and 1.9% after exposure on
      Oxford Street; P=0.003). The changes were associated most consistently with
      exposures to ultrafine particles and elemental carbon. CONCLUSIONS: Our
      observations serve as a demonstration and explanation of the epidemiologic
      evidence that associates the degree of traffic exposure with lung function in
      asthma.

PMID- 18057338
TI  - Metabolic effects of a growth hormone-releasing factor in patients with HIV.
AB  - BACKGROUND: Visceral adipose tissue accumulates during antiretroviral therapy in
      many patients who are infected with the human immunodeficiency virus (HIV); this
      process is associated with an increased cardiovascular risk. We assessed the use
      of a growth hormone-releasing factor analogue, tesamorelin, to decrease visceral
      adiposity. METHODS: We randomly assigned 412 patients with HIV (86% of whom were
      men) who had an accumulation of abdominal fat to receive a daily subcutaneous
      injection of either 2 mg of tesamorelin or placebo for 26 weeks. The primary end
      point was the percent change from baseline in visceral adipose tissue as shown on
      computed tomography. Secondary end points included triglyceride levels, the ratio
      of total cholesterol to high-density lipoprotein (HDL) cholesterol, the level of
      insulin-like growth factor I (IGF-I), and self-assessed body image. Glycemic
      measures included glucose and insulin levels. RESULTS: The measure of visceral
      adipose tissue decreased by 15.2% in the tesamorelin group and increased by 5.0%
      in the placebo group; the levels of triglycerides decreased by 50 mg per
      deciliter and increased by 9 mg per deciliter, respectively, and the ratio of
      total cholesterol to HDL cholesterol decreased by 0.31 and increased by 0.21,
      respectively (P<0.001 for all comparisons). Levels of total cholesterol and HDL
      cholesterol also improved significantly in the tesamorelin group. Levels of IGF-I
      increased by 81.0% in the tesamorelin group and decreased by 5.0% in the placebo
      group (P<0.001). Adverse events did not differ significantly between the two
      study groups, but more patients in the tesamorelin group withdrew from the study
      because of an adverse event. No significant differences were observed in glycemic
      measures. CONCLUSIONS: Daily tesamorelin for 26 weeks decreased visceral fat and
      improved lipid profiles, effects that might be useful in HIV-infected patients
      who have treatment-associated central fat accumulation. (ClinicalTrials.gov
      number, NCT00123253 [ClinicalTrials.gov] .).

PMID- 18057339
TI  - Adolescent overweight and future adult coronary heart disease.
AB  - BACKGROUND: The effect of adolescent overweight on future adult coronary heart
      disease (CHD) is not known. METHODS: We estimated the prevalence of obese 35-year
      olds in 2020 on the basis of adolescent overweight in 2000 and historical trends
      regarding overweight adolescents who become obese adults. We then used the CHD
      Policy Model, a state-transition computer simulation of U.S. residents who are 35
      years of age or older, to project the annual excess incidence and prevalence of
      CHD, the total number of excess CHD events, and excess deaths from both CHD and
      other causes attributable to obesity from 2020 to 2035. We also modeled the
      effect of treating obesity-related increases in blood pressure and dyslipidemia.
      RESULTS: Adolescent overweight is projected to increase the prevalence of obese
      35-year-olds in 2020 to a range of 30 to 37% in men and 34 to 44% in women. As a
      consequence of this increased obesity, an increase in the incidence of CHD and in
      the total number of CHD events and deaths is projected to occur in young
      adulthood. The increase is projected to continue in both absolute and relative
      terms as the population reaches middle age. By 2035, it is estimated that the
      prevalence of CHD will increase by a range of 5 to 16%, with more than 100,000
      excess cases of CHD attributable to the increased obesity. Aggressive treatment
      with currently available therapies to reverse modifiable obesity-related risk
      factors would reduce, but not eliminate, the projected increase in the number of
      CHD events. CONCLUSIONS: Although projections 25 or more years into the future
      are subject to innumerable uncertainties, extrapolation from current data
      suggests that adolescent overweight will increase rates of CHD among future young
      and middle-aged adults, resulting in substantial morbidity and mortality.

PMID- 18057340
TI  - Cochlear implants for children with severe-to-profound hearing loss.

PMID- 18057341
TI  - Images in clinical medicine. Lingua villosa nigra.

PMID- 18057342
TI  - Clinical problem-solving. The leading diagnosis--a 23-year-old black woman
      presented to the emergency department with diffuse, colicky abdominal pain of 1
      hour's duration.

PMID- 18057343
TI  - Health effects of airborne particulate matter.

PMID- 18057344
TI  - Manipulation of the growth hormone axis in patients with HIV infection.

PMID- 18057345
TI  - Molecules that mediate mood.

PMID- 18057346
TI  - Dronedarone in atrial fibrillation.

PMID- 18057347
TI  - Shattuck Lecture: improving American health.

PMID- 18057348
TI  - Control of neglected tropical diseases.

PMID- 18057349
TI  - Myocardial reperfusion injury.

PMID- 18057350
TI  - Anabolic therapies for osteoporosis.

PMID- 18057351
TI  - Growth of a meningioma in a transsexual patient after estrogen-progestin therapy.

PMID- 18057352
TI  - Inhibition of fracture healing.
AB  - This paper reviews the current literature concerning the main clinical factors
      which can impair the healing of fractures and makes recommendations on avoiding
      or minimising these in order to optimise the outcome for patients. The clinical
      implications are described.

PMID- 18057353
TI  - Total hip replacement in renal transplant patients.
AB  - Avascular necrosis of the femoral head creates considerable morbidity in
      successful renal transplant recipients who are generally young and expect active
      lifestyles. Total hip replacement is considered the treatment of choice in these
      patients, but surgeons may be wary because of a supposed increase in the risk of
      infection and other complications. A review of the literature reveals that
      cemented hip arthroplasty provides good to excellent functional outcomes for
      renal transplant patients. Most authors have found that the risk of infection is
      not increased despite chronic immunosuppression, but the rates of general
      complications are and should be anticipated and treated. There is a high rate of
      early failure in these patients because of their young age and diffuse osteopenia
      as a result of secondary hyperparathyroidism related to the underlying renal
      disease and chronic steroid use. Recent studies have found that despite decreased
      bone stock in these patients, porous-coated prostheses are not contraindicated.

PMID- 18057354
TI  - Key factors for a successful National Arthroplasty Register.
AB  - Since the introduction of the first National Arthroplasty Register in Sweden in
      1975, many other countries have tried to adopt the successful Scandinavian
      system. However, not all have overcome the political and practical difficulties
      of establishing a working register. We have surveyed the current registries to
      establish the key factors required for an effective database. We have received
      detailed information from 15 arthroplasty registers worldwide. The legal
      conditions under which they operate together with the methods of collection and
      handling of the data differ widely, but the fulfilment of certain criteria is
      necessary achieve a high degree of completeness of the data to ensure the
      provision of statistically relevant information.

PMID- 18057355
TI  - Medium- and long-term performance of 11,516 uncemented primary femoral stems from
      the Norwegian arthroplasty register.
AB  - Primary uncemented femoral stems reported to the Norwegian arthroplasty register
      between 1987 and 2005 were included in this prospective observational study.
      There were 11 516 hips (9679 patients) and 14 different designs of stem. Kaplan
      Meier survival probabilities and Cox regression were used to analyse the data.
      With aseptic loosening as the end-point, all currently used designs performed
      excellently with survival of 96% to 100% at ten years. With the end-point as stem
      revision for any cause, the long-term results of the different designs varied
      from poor to excellent, with survival at 15 years ranging between 29% and 97%.
      Follow-up for longer than seven years was needed to identify some of the poorly
      performing designs. There were differences between the stems; the Corail, used in
      5456 hips, was the most frequently used stem with a survival of 97% at 15 years.
      Male gender was associated with an increased risk of revision of x 1.3 (95%
      confidence interval 1.05 to 1.52), but age and diagnosis had no influence on the
      results. Overall, modern uncemented femoral stems performed well. Moderate
      differences in survival between well-performing stems should be interpreted with
      caution since the differences may be caused by factors other than the stem
      itself.

PMID- 18057356
TI  - The use of a posterior lip augmentation device for a revision of recurrent
      dislocation after primary cemented Charnley/Charnley Elite total hip replacement:
      results at a mean follow-up of six years and nine months.
AB  - Between April 1992 and July 2005, 310 posterior lip augmentation devices were
      used for the treatment of recurrent dislocation of the hip in 307 patients who
      had received primary total hip replacements (THRs) using Charnley/Charnley Elite
      components with a cemented acetabulum. The mean number of dislocations before
      stabilisation with the device was five (1 to 16) with a mean time to this
      intervention from the first dislocation of 3.8 years (0 days to 22.5 years). The
      mean age of the patients at this reconstruction was 75.4 years (39 to 96). A
      retrospective clinical and radiological review was carried out at a mean follow
      up of six years and nine months (4.4 months to 13 years and 7 months). Of the 307
      patients, 53 had died at the time of the latest review, with a functioning THR
      and with the posterior lip augmentation device in situ. There were four revisions
      (1.3%), one for pain, two for deep infection and one for loosening of the
      acetabular component. Radiolucent lines around the acetabular component increased
      in only six cases after insertion of the device which was successful in
      eliminating instability in 302 patients, with only five further dislocations
      (1.6%) occurring after its insertion.

PMID- 18057357
TI  - Three-dimensional custom-designed cementless femoral stem for osteoarthritis
      secondary to congenital dislocation of the hip.
AB  - A clinical and radiological study was conducted on 97 total hip replacements
      performed for congenital hip dislocation in 79 patients between 1989 and 1998
      using a three-dimensional custom-made cementless stem. The mean age at operation
      was 48 years (17 to 72) and the mean follow-up was for 123 months (83 to 182).
      According to the Crowe classification, there were 37 class I, 28 class II, 13
      class III and 19 class IV hips. The mean leg lengthening was 25 mm (5 to 58), the
      mean pre-operative femoral anteversion was 38.6 degrees (2 degrees to 86 degrees
      ) and the mean correction in the prosthetic neck was -23.6 degrees (-71 degrees
      to 13 degrees ). The mean Harris hip score improved from 58 (15 to 84) to 93 (40
      to 100) points. A revision was required in six hips (6.2%). The overall survival
      rate was 89.5% (95% confidence interval 89.2 to 89.8) at 13 years when two hips
      were at risk. This custom-made cementless femoral component, which can be
      accommodated in the abnormal proximal femur and will correct the anteversion and
      frontal offset, provided good results without recourse to proximal femoral
      corrective osteotomy.

PMID- 18057358
TI  - Radiological evidence of femoroacetabular impingement in mild slipped capital
      femoral epiphysis: a mean follow-up of 14.4 years after pinning in situ.
AB  - Conventional treatment of mild slipped capital femoral epiphysis consists of
      fixation in situ with wires or screws. Recent contributions to the literature
      suggest that even a mild slip may lead to early damage of the acetabular labrum
      and adjacent cartilage by abutment of a prominent femoral metaphysis. It has been
      suggested that the appropriate treatment in mild slipped capital femoral
      epiphysis should not only prevent further slipping of the epiphysis, but also
      address potential femoroacetabular impingement by restoring the anatomy of the
      proximal femur. Between October 1984 and December 1995 we treated 16 patients for
      unilateral mild slipped capital femoral epiphysis by fixation in situ with
      Kirschner wires. In this study we have reviewed these patients for clinical and
      radiological evidence of femoroacetabular impingement. There was little clinical
      indication of impingement but radiological evaluation assessing the femoral head
      neck ratio and measuring the Notzli alpha angle on the anteroposterior and cross
      table radiographs showed significant alterations in the proximal femur. None of
      the affected hips had a normal head-neck ratio and the mean alpha angle was 86
      degrees (55 degrees to 99 degrees ) and 55 degrees (40 degrees to 94 degrees ) on
      the anteroposterior and lateral cross-table radiographs, respectively. While our
      clinical data favours conventional treatment, our radiological findings are in
      support of restoring the anatomy of the proximal femur to avoid or delay the
      development of femoroacetabular impingement following mild slipped capital
      femoral epiphysis.

PMID- 18057359
TI  - The influence of the presence and severity of pre-existing patellofemoral
      degenerative changes on the outcome of the Oxford medial unicompartmental knee
      replacement.
AB  - Patellofemoral joint degeneration is often considered a contraindication to
      medial unicompartmental knee replacement. We examined the validity of this
      preconception using information gathered prospectively on the intra-operative
      status of the patellofemoral joint in 824 knees in 793 consecutive patients who
      underwent Oxford unicondylar knee replacement for anteromedial osteoarthritis.
      All operations were performed between January 1998 and September 2005. A five
      point grading system classified degeneration of the patellofemoral joint from
      none to full-thickness cartilage loss. A subclassification of the presence or
      absence of any full-thickness cartilage loss was subsequently performed to test
      selected hypotheses. Outcome was evaluated independently by physiotherapists
      using the Oxford and the American Knee Society Scores with a minimum follow-up of
      one year. Full-thickness cartilage loss on the trochlear surface was observed in
      100 of 785 knees (13%), on the medial facet of the patella in 69 of 782 knees
      (9%) and on the lateral facet in 29 of 784 knees (4%). Full-thickness cartilage
      loss at any location was seen in 128 knees (16%) and did not produce a
      significantly worse outcome than those with a normal or near-normal joint
      surface. The severity of the degeneration at any of the intra-articular locations
      also had no influence on outcome. We concluded that, provided there is not bone
      loss and grooving of the lateral facet, damage to the articular cartilage of the
      patellofemoral joint to the extent of full-thickness cartilage loss is not a
      contraindication to the Oxford mobile-bearing unicompartmental knee replacement.

PMID- 18057360
TI  - Pre-operative clinical and radiological assessment of the patellofemoral joint in
      unicompartmental knee replacement and its influence on outcome.
AB  - Anterior knee pain and/or radiological evidence of degeneration of the
      patellofemoral joint are considered to be contraindications to unicompartmental
      knee replacement. The aim of this study was to determine whether this is the
      case. Between January 2000 and September 2003, in 100 knees (91 patients) in
      which Oxford unicompartmental knee replacements were undertaken for anteromedial
      osteoarthritis, pre-operative anterior knee pain and the radiological status of
      the patellofemoral joint were defined using the Altman and Ahlback systems.
      Outcome was evaluated at two years with the Oxford knee score and the American
      Knee Society score. Pre-operatively 54 knees (54%) had anterior knee pain. The
      clinical outcome was independent of the presence or absence of pre-operative
      anterior knee pain. Degenerative changes of the patellofemoral joint were seen in
      54 patients (54%) on the skyline radiographs, including ten knees (10%) with
      joint space obliteration. Patients with medial patellofemoral degeneration had a
      similar outcome to those without. For some outcome measures patients with lateral
      patellofemoral degeneration had a worse score than those without, but these
      patients still had a good outcome, with a mean Oxford knee score of 37.6 (SD
      9.5). These results show that neither anterior knee pain nor radiologically
      demonstrated medial patellofemoral joint degeneration should be considered a
      contraindication to Oxford unicompartmental knee replacement. With lateral
      patellofemoral degeneration the situation is less well defined and caution should
      be observed.

PMID- 18057361
TI  - A randomised controlled trial of cemented versus cementless press-fit condylar
      total knee replacement: 15-year survival analysis.
AB  - We report the long-term survival of a prospective randomised consecutive series
      of 501 primary knee replacements using the press-fit condylar posterior cruciate
      ligament-retaining prosthesis. Patients received either cemented (219 patients,
      277 implants) or cementless (177 patients, 224 implants) fixation. Altogether, 44
      of 501 knees (8.8%) underwent revision surgery (24 cemented vs 20 cementless).
      For cemented knees the 15-year survival rate was 80.7% (95% confidence interval
      (CI) 71.5 to 87.4) and for cementless knees it was 75.3% (95% CI 63.5 to 84.3).
      There was no significant difference between the two groups (cemented vs
      cementless; hazard ratio (HR) 0.83, 95% CI 0.45 to 1.52, p = 0.55). When
      comparing the covariates there was no significant difference in the rates of
      survival between the side of operation (HR 0.58, p = 0.07), age (HR 0.97, p =
      0.10) and diagnosis (HR 1.25 p = 0.72). However, there was a significant gender
      difference, with males having a higher failure rate with cemented fixation (HR
      2.48, p = 0.004). Females had a similar failure rate in both groups. This single
      surgeon series, with no loss to follow-up, provides reliable data of the revision
      rates of one of the most commonly-used total knee replacements. The survival of
      the press-fit condylar total knee replacement remained good at 15 years,
      irrespective of the method of fixation.

PMID- 18057362
TI  - The management of cubitus varus and valgus using the Ilizarov method.
AB  - Cubitus varus and valgus are the most common complications of supracondylar and
      lateral condylar fractures. Various combinations of osteotomy and fixation have
      been described to correct these deformities but each is associated with
      significant complications. In this study, we used distraction osteogenesis and
      Ilizarov frame fixation to treat 24 elbows in 23 patients with cubitus varus or
      valgus. Their clinical outcome was evaluated using the protocol of Bellemore et
      al. The mean time to follow-up was 18.3 months (10 to 36) and the mean time to
      frame removal was 13.5 weeks (8 to 20). The mean carrying angle was corrected
      from -18.7 degrees (-10 degrees to -30 degrees ) to 6.1 degrees (2 degrees to 10
      degrees ) in patients with cubitus varus and from 36.5 degrees (25 degrees to 45
      degrees ) to 9.4 degrees (4 degrees to 15 degrees ) in patients with cubitus
      valgus. There were 18 excellent and six good results. The Ilizarov method with
      gradual distraction is a safe, stable, adjustable and versatile method of
      treating deformities at the elbow without the problems of an unsightly scar or
      limited range of movement, and gives a good clinical and radiological outcome.
      Tardy ulnar nerve palsy should be treated first by anterior transposition.

PMID- 18057363
TI  - Fusion of the wrist in rheumatoid arthritis: a clinical and functional evaluation
      of two surgical techniques.
AB  - We retrospectively compared wrist arthrodesis using the Mannerfelt technique in
      19 or an AO-plate in 23 patients with long-standing rheumatoid arthritis. The
      mean follow-up was for 76 months. Compared with the Mannerfelt fusion group,
      patients in the AO-plate group reported greater satisfaction with their wrist
      function (74% vs 37%, p = 0.015). Complications were reported in six wrists in
      the AO-plate group and two wrists in the Mannerfelt fusion group (p = 0.258). At
      final follow-up, 95% of patients (41) reported either no pain or only mild pain.
      There was improvement in flexion of the finger joints in both groups but no
      significant improvement in the extension lag in either group. Both methods
      relieve pain and improve function. Overall, the activities of daily living scores
      and the patients' subjective assessment of outcome tended to be higher in the AO
      plate group than in the Mannerfelt fusion group, although the difference was not
      statistically significant. Similarly, although more postoperative complications
      occurred in the AO-plate group, the difference between the two groups was not
      statistically significant.

PMID- 18057364
TI  - Rates of fracture in participants and non-participants in the Osteoporosis
      Prospective Risk Assessment study.
AB  - We invited 1604 randomly selected women, all 75 years of age, to participate in a
      study on the risk factors for fracture. The women were divided into three groups
      consisting of 1044 (65%) who attended the complete study, 308 (19%) respondents
      to the study questionnaire only and 252 (16%) who did not respond. The occurrence
      of the life-time fracture was ascertained from radiological records in all groups
      and by questionnaires from the attendees and respondents. According to the
      radiological records, fewer of the questionnaire respondents (88 of 308, 28.6%)
      and non-respondents (68 of 252, 27%) had sustained at least one fracture when
      compared with the attendees (435 of 1044, 41.7%; chi-squared test, p < 0.001).
      According to the questionnaire, fewer of the respondents (96 of 308, 31.1%) had
      sustained at least one previous fracture when compared with the attendees (457 of
      1044, 43.7%; chi-squared test, p < 0.001). Any study concerning the risk of
      fracture may attract those with experience of a fracture which explains the
      higher previous life-time incidence among the attendees. This factor may cause
      bias in epidemiological studies.

PMID- 18057365
TI  - The long-term results of endoprosthetic replacement of the proximal tibia for
      bone tumours.
AB  - We have investigated whether improvements in design have altered the outcome for
      patients undergoing endoprosthetic replacement of the proximal tibia following
      resection of a tumour. Survival of the implant and 'servicing' procedures have
      been documented using a prospective database. A total of 194 patients underwent a
      proximal tibial replacement, with 95 having a fixed-hinge design and 99 a
      rotating-hinge with a hydroxyapatite collar; their median age was 21.5 years (10
      to 74). At a mean follow-up of 14.7 years (5 to 29), 115 patients remain alive.
      The risk of revision for any reason in the fixed-hinge group was 32% at five
      years, 61% at ten years and 75% at 15 and 20 years, and in the rotating-hinge
      group 12% at five years, 25% at ten years and 30% at 15 years. Aseptic loosening
      was the most common reason for revision in the fixed-hinge knees, fracture of the
      implant in the early design of rotating hinges and infection in the current
      version. The risk of revision for aseptic loosening in the fixed-hinge knees was
      46% at ten years. This was reduced to 3% in the rotating-hinge knee with a
      hydroxyapatite collar. The cemented, rotating hinge design currently offers the
      best chance of long-term survival of the prosthesis.

PMID- 18057366
TI  - Surgical correction of the medial rotation contracture in obstetric brachial
      plexus palsy.
AB  - The medial rotation contracture caused by weak external rotation secondary to
      obstetric brachial plexus injury leads to deformation of the bones of the
      shoulder. Scapular hypoplasia, elevation and rotation deformity are accompanied
      by progressive dislocation of the humeral head. Between February and August 2005,
      44 children underwent a new surgical procedure called the 'triangle tilt'
      operation to correct this bony shoulder deformity. Surgical levelling of the
      distal acromioclavicular triangle combined with tightening of the posterior
      glenohumeral capsule (capsulorrhaphy) improved shoulder function and corrected
      the glenohumeral axis in these patients. The posture of the arm at rest was
      improved and active external rotation increased by a mean of 53 degrees (0
      degrees to 115 degrees ) in the 40 children who were followed up for more than
      one year. There was a mean improvement of 4.9 points (1.7 to 8.3) of the Mallet
      shoulder function score after surgical correction of the bony deformity.

PMID- 18057367
TI  - The 'four-in-one' procedure for habitual dislocation of the patella in children:
      early results in patients with severe generalised ligamentous laxity and aplasis
      of the trochlear groove.
AB  - We describe our experience with the 'four-in-one' procedure for habitual
      dislocation of the patella in five children (six knees). All the patients
      presented with severe generalised ligamentous laxity and aplasia of the trochlear
      groove. All had a lateral release, proximal 'tube' realignment of the patella,
      semitendinosus tenodesis and transfer of the patellar tendon. The mean age at the
      time of the operation was 6.1 years (4.9 to 6.9), and the patients were followed
      up for a mean of 54.5 months (31 to 66). The clinical results were evaluated
      using the Kujala score. There has been no recurrence of dislocation. All the
      patients have returned to full activities and the parents and children were
      satisfied with the clinical results. The mean Kujala score was 95.3 (88 to 98).
      Two patients had marginal skin necrosis which healed after debridement and
      secondary closure. These early results in this small group have shown that the
      'four-in-one' procedure is effective in the treatment of obligatory dislocation
      of the patella in children with severe ligamentous laxity and trochlear aplasia.

PMID- 18057368
TI  - Percutaneous screw fixation for sacral insufficiency fractures: a review of three
      cases.
AB  - Sacral insufficiency fractures are traditionally treated with bed rest and
      analgesia. The importance of early rehabilitation is generally appreciated; but
      pain frequently delays this, resulting in prolonged hospital stay and the risk of
      complications related to immobility. We describe three women with sacral
      insufficiency fractures who were treated with percutaneous sacroiliac screws and
      followed up for a mean of 18 months (12 to 24). They had immediate pain relief,
      uncomplicated rehabilitation and uneventful healing.

PMID- 18057369
TI  - The effect of metal ions in solution on bacterial growth compared with wear
      particles from hip replacements.
AB  - The biological significance of cobalt-chromium wear particles from metal-on-metal
      hip replacements may be different to the effects of the constituent metal ions in
      solution. Bacteria may be able to discriminate between particulate and ionic
      forms of these metals because of a transmembrane nickel/cobalt-permease. It is
      not known whether wear particles are bacteriocidal. We compared the doubling time
      of coagulase negative staphylococcus, Staphylococcus aureus and methicillin
      resistant S. aureus when cultured in either wear particles from a metal-on-metal
      hip simulator, wear particles from a metal-on-polyethylene hip simulator, metal
      ions in solution or a control. Doubling time halved in metal-on-metal (p = 0.003)
      and metal-on-polyethylene (p = 0.131) particulate debris compared with the
      control. Bacterial nickel/cobalt-transporters allow metal ions but not wear
      particles to cross bacterial membranes. This may be useful for testing the
      biological characteristics of different wear debris. This experiment also shows
      that metal-on-metal hip wear debris is not bacteriocidal.

PMID- 18057370
TI  - Ankle joint pressure in pes cavovarus.
AB  - A cavovarus foot deformity was simulated in cadaver specimens by inserting
      metallic wedges of 15 degrees and 30 degrees dorsally into the first
      tarsometatarsal joint. Sensors in the ankle joint recorded static tibiotalar
      pressure distribution at physiological load. The peak pressure increased
      significantly from neutral alignment to the 30 degrees cavus deformity, and the
      centre of force migrated medially. The anterior migration of the centre of force
      was significant for both the 15 degrees (repeated measures analysis of variance
      (ANOVA), p = 0.021) and the 30 degrees (repeated measures ANOVA, p = 0.007) cavus
      deformity. Differences in ligament laxity did not influence the peak pressure.
      These findings support the hypothesis that the cavovarus foot deformity causes an
      increase in anteromedial ankle joint pressure leading to anteromedial arthrosis
      in the long term, even in the absence of lateral hindfoot instability.

PMID- 18057371
TI  - The effects of the sympathetic nerves on lumbar radicular pain: a behavioural and
      immunohistochemical study.
AB  - A rat model of lumbar root constriction with an additional sympathectomy in some
      animals was used to assess whether the sympathetic nerves influenced radicular
      pain. Behavioural tests were undertaken before and after the operation. On the
      28th post-operative day, both dorsal root ganglia and the spinal roots of L4 and
      L5 were removed, frozen and sectioned on a cryostat (8 microm to 10 microm).
      Immunostaining was then performed with antibodies to tyrosine hydroxylase (TH)
      according to the Avidin Biotin Complex method. In order to quantify the presence
      of sympathetic nerve fibres, we counted TH-immunoreactive fibres in the dorsal
      root ganglia using a light microscope equipped with a micrometer graticule (10 x
      10 squares, 500 mm x 500 mm). We counted the squares of the graticule which
      contained TH-immunoreactive fibres for each of five randomly-selected sections of
      the dorsal root ganglia. The root constriction group showed mechanical allodynia
      and thermal hyperalgesia. In this group, TH-immunoreactive fibres were abundant
      in the ipsilateral dorsal root ganglia at L5 and L4 compared with the opposite
      side. In the sympathectomy group, mechanical hypersensitivity was attenuated
      significantly. We consider that the sympathetic nervous system plays an important
      role in the generation of radicular pain.

PMID- 18057372
TI  - Survival and clinical outcome of SB Charite III disc replacement for back pain.

PMID- 18057373
TI  - Survival and clinical outcome of SB Charite III disc replacement for back pain.

PMID- 18057374
TI  - Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in
      healthy subjects.
AB  - We evaluated the impact of gender differences in both the quantitative and
      qualitative features of HDL subspecies on cellular free cholesterol efflux
      through the scavenger receptor class B type I (SR-BI), ABCA1, and ABCG1 pathways.
      For that purpose, healthy subjects (30 men and 26 women) matched for age, body
      mass index, triglyceride, apolipoprotein A-I, and high density lipoprotein
      cholesterol (HDL-C) levels were recruited. We observed a significant increase
      (+14%; P < 0.03) in the capacity of whole sera from women to mediate cellular
      free cholesterol efflux via the SR-BI-dependent pathway compared with sera from
      men. Such enhanced efflux capacity resulted from a significant increase in plasma
      levels of large cholesteryl ester-rich HDL2 particles (+20%; P < 0.04) as well as
      from an enhanced capacity (+14%; P < 0.03) of these particles to mediate cellular
      free cholesterol efflux via SR-BI. By contrast, plasma from men displayed an
      enhanced free cholesterol efflux capacity (+31%; P < 0.001) via the ABCA1
      transporter pathway compared with that from women, which resulted from a 2.4-fold
      increase in the plasma level of prebeta particles (P < 0.008). Moreover, in
      women, SR-BI-mediated cellular free cholesterol efflux was significantly
      correlated with plasma HDL-C (r = 0.72, P < 0.0001), whereas this relationship
      was not observed in men. In conclusion, HDL-C level may not represent the
      absolute indicator of the efficiency of the initial step of the reverse
      cholesterol transport.

PMID- 18057375
TI  - Consensus guidelines for the diagnosis and treatment of adults with GH deficiency
      II: a statement of the GH Research Society in association with the European
      Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of
      Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia.
AB  - OBJECTIVE: The GH Research Society held a Consensus Workshop in Sydney,
      Australia, 2007 to incorporate the important advances in the management of GH
      deficiency (GHD) in adults, which have taken place since the inaugural 1997
      Consensus Workshop. METHOD: Two commissioned review papers, previously published
      Consensus Statements of the Society and key questions were circulated before the
      Workshop, which comprised a rigorous structure of review with breakout discussion
      groups. A writing group transcribed the summary group reports for drafting in a
      plenary forum on the last day. All participants were sent a polished draft for
      additional comments and gave signed approval to the final revision. CONCLUSION:
      Testing for GHD should be extended from hypothalamic-pituitary disease and
      cranial irradiation to include traumatic brain injury. Testing may indicate
      isolated GHD; however, idiopathic isolated GHD occurring de novo in the adult is
      not a recognized entity. The insulin tolerance test, combined administration of
      GHRH with arginine or growth hormone-releasing peptide, and glucagon are
      validated GH stimulation tests in the adult. A low IGF-I is a reliable diagnostic
      indicator of GHD in the presence of hypopituitarism, but a normal IGF-I does not
      rule out GHD. GH status should be reevaluated in the transition age for continued
      treatment to complete somatic development. Interaction of GH with other axes may
      influence thyroid, glucocorticoid, and sex hormone requirements. Response should
      be assessed clinically by monitoring biochemistry, body composition, and quality
      of life. There is no evidence that GH replacement increases the risk of tumor
      recurrence or de novo malignancy.

PMID- 18057376
TI  - Cut-off limits of the GH response to GHRH plus arginine test and IGF-I levels for
      the diagnosis of GH deficiency in late adolescents and young adults.
AB  - OBJECTIVE: To define the appropriate diagnostic cut-off limits for the GH
      response to GHRH+arginine (ARG) test and IGF-I levels, using receiver operating
      characteristics (ROC) curve analysis, in late adolescents and young adults.
      DESIGN AND METHODS: We studied 152 patients with childhood-onset organic
      hypothalamic-pituitary disease (85 males, age (mean+/-s.e.m.): 19.2+/-0.2 years)
      and 201 normal adolescents as controls (96 males, age: 20.7+/-0.2 years).
      Patients were divided into three subgroups on the basis of the number of the
      other pituitary hormone deficits, excluding GH deficiency (GHD): subgroup A
      consisted of 35 panhypopituitary patients (17 males, age: 21.2+/-0.4 years),
      subgroup B consisted of 18 patients with only one or with no more than two
      pituitary hormone deficits (7 males, age: 20.2+/-0.9 years); and subgroup C
      consisted of 99 patients without any known hormonal pituitary deficits (60 males,
      age: 18.2+/-0.2 years). Both patients and controls were lean (body mass index,
      BMI<25 kg/m(2)). Patients in subgroup A were assumed to be GHD, whereas in
      patients belonging to subgroups B and C the presence of GHD had to be verified.
      RESULTS: For the GHRH+ARG test, the best pair of highest sensitivity (Se; 100%)
      and specificity (Sp; 97%) was found choosing a peak GH of 19.0 microg/l. For IGF
      I levels, the best pair of highest Se (96.6%) and Sp (74.6%) was found using a
      cut-off point of 160 microg/l (SDS: -1.3). Assuming 19.0 microg/l to be the cut
      off point established for GHRH+ARG test, 72.2% of patients in subgroup B and
      39.4% in subgroup C were defined as GHD. In patients belonging to group B and C
      and with a peak GH response <19 microg/l to the test, IGF-I levels were lower
      than 160 microg/l (or less than 1.3 SDS) in 68.7 and 41.6% of patients
      respectively predicting severe GHD in 85.7% of panhypopituitary patients
      (subgroup A). CONCLUSIONS: In late adolescent and early adulthood patients, a GH
      cut-off limit using the GHRH+ARG test lower than 19.0 microg/l is able to
      discriminate patients with a suspicion of GHD and does not vary from infancy to
      early adulthood.

PMID- 18057377
TI  - Administration route-dependent effects of estrogens on IGF-I levels during fixed
      GH replacement in women with hypopituitarism.
AB  - OBJECTIVE: GH-deficient women using oral estradiol treatment require higher doses
      of recombinant human GH (rhGH) to achieve similar IGF-I levels when compared with
      men and women on transdermal estradiol replacement. The aim of this study was to
      evaluate the effects of oral versus transdermal estrogen administration at
      similar plasma estradiol levels on IGF-I, IGF-binding protein-3, and sex hormone
      binding globulin (SHBG) concentrations. DESIGN: Parallel crossover study in which
      two groups of hypogonadal and GH-deficient women with fixed and stable rhGH
      replacement passed through four different estradiol treatment schemes (2 and 4 mg
      oral, and 50 and 100 microg transdermal estradiol) with a duration of four cycles
      each to ensure a new steady state. Group I (18 patients using oral estradiol
      prior to the study) was treated with oral followed by transdermal estradiol and
      group II (five patients with transdermal estradiol prior to inclusion) with
      transdermal followed by oral estradiol. RESULTS: Estradiol concentrations were
      lowest during 50 microg transdermal and highest during 4 mg oral estradiol
      treatment. Estradiol concentrations did not differ during 100 microg transdermal
      and 2 mg oral treatment. Nevertheless, IGF-I levels were significantly higher
      during 100 microg transdermal when compared with 2 mg oral treatment (P=0.005 in
      group I and 0.02 in group II), while SHBG levels were significantly lower
      (P=0.002 in group I and P=0.004 in group II). SHBG and IGF-I concentrations were
      negatively correlated (R=-0.41, P=0.0001). CONCLUSION: During fixed GH
      replacement, the route of estrogen administration is a determinant of IGF-I
      levels in hypogonadal GH-deficient women.

PMID- 18057379
TI  - Limitations of nocturnal salivary cortisol and urine free cortisol in the
      diagnosis of mild Cushing's syndrome.
AB  - OBJECTIVE: Cushing's syndrome (CS) is difficult to diagnose due to its
      nonspecific presentation. Diagnostic tests like 24-h urine free cortisol (UFC)
      and the overnight 1 mg dexamethasone suppression test (DST) lack sufficient
      sensitivity and specificity. Measurement of nocturnal salivary cortisol (NSC) is
      an accurate and reproducible test with a high sensitivity for CS. However, its
      performance in mild CS has not been reported. We present 11 cases of CS with
      normal or mildly elevated UFC in whom NSC was helpful in making a diagnosis.
      DESIGN AND METHODS: All patients had at least one collection of 24-h UFC and NSC
      and eight had an overnight 1 mg DST. The number of NSC measurements per patient
      was determined by the clinical index of suspicion and the results of initial
      testing. Imaging studies included magnetic resonance imaging (MRI) of pituitary
      or computer tomography scan of abdomen. RESULTS: Only four out of eleven patients
      had elevations in UFC and none were >2 times the upper limit of normal. Seven out
      of eight had an abnormal DST. All patients had some elevated NSCs (14-100%). Out
      of eleven patients, six had an abnormality in the pituitary gland found by MRI
      and two out of eleven had adrenal masses. The remaining three had normal
      pituitary MRI but had inferior petrosal sinus (IPS) sampling indicating Cushing's
      disease. All patients had appropriate surgery, and histopathology of all except
      one was suggestive of either a cortisol-producing adrenal adenoma or an ACTH
      secreting pituitary adenoma. CONCLUSION: Neither a normal UFC nor a normal NSC
      excludes mild CS. Multiple samples (urine/saliva) and DST are needed to make the
      diagnosis of mild CS.

PMID- 18057378
TI  - Differential gene expression in ACTH -secreting and non-functioning pituitary
      tumors.
AB  - OBJECTIVE: Differential expression of several genes between ACTH-secreting
      pituitary tumors causing Cushing' disease (CD), silent corticotroph adenoma
      (SCA), and non-functioning pituitary tumors (NFT) was investigated. DESIGN AND
      METHODS: We used tissue specimens from 35 pituitary tumors (12 CD, 8 SCA, and 15
      NFT). Steady-state mRNA levels of the genes related to proopiomelanocortin (POMC)
      transcription, synthesis, processing, and secretion, such as neurogenic
      differentiation 1 (NeuroD1), T-box 19 (Tpit), corticotropin releasing hormone
      receptor (CRHR), vasopressin receptor 1b (V1bR), prohormone convertase (PC) 1/3
      and PC2, 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2,
      glucocorticoid receptor alpha (GRalpha), annexin A1, histone deacetylase 2
      (HDAC2), and BRM/SWI2-related gene 1, were determined by real-time RT-PCR.
      RESULTS AND CONCLUSION: POMC and Tpit mRNA levels were greater in CD and SCA than
      those in NFT. NeuroD1 mRNA levels were less in CD than those in NFT, but almost
      comparable between SCA and NFT. PC1/3 mRNA levels were greater in CD, but less in
      SCA than those in NFT. PC2 mRNA levels in CD and SCA were less than those in NFT.
      CRHR, V1bR, and 11beta-HSD2 mRNA levels in CD were greater than those in SCA and
      NFT. HDAC2 mRNA levels in CD and SCA were lower than those in NFT. In conclusion,
      our study demonstrated that the genes related to transcription, synthesis,
      processing, and secretion of POMC are differentially regulated in ACTH-secreting
      pituitary tumors causing CD and SCA compared with those in NFT. This may partly
      explain the development of clinically active and inactive CD.

PMID- 18057380
TI  - Endocrine and metabolic responses to extreme altitude and physical exercise in
      climbers.
AB  - CONTEXT: Chronic hypoxia induces complex metabolic and endocrine adaptations.
      High-altitude (HA) exposure is a physiological model of hypoxia. OBJECTIVE: To
      further investigate the endocrine and metabolic responses to extreme HA. METHODS:
      We studied nine male elite climbers at sea level and at 5200 m after climbing Mt.
      Everest. RESULTS: After 7 weeks at HA, body weight was reduced (P<0.05);
      regarding endocrine variables we observed: a) an increase of 2-h mean GH
      concentration (P<0.05) as well as of total IGF-I and IGF binding protein-3 levels
      (P<0.05 for both); b) a prolactin increase (P<0.05) coupled with testosterone
      decrease (P<0.01) and progesterone increase (P<0.05) without any change in
      estradiol levels: c) no change in cortisol, ACTH, and dehydroepiandrosterone
      sulfate (DHEAS) levels; d) an increase in free thyroxine (P<0.05) and free tri
      iodothyronine (T(3)) decrease (P<0.05) but no change in TSH levels; e) a plasma
      glucose decrease (P<0.05) without any change in insulin levels; f) an increase in
      mean free fatty acid levels (P<0.05); g) despite body weight loss, leptin levels
      showed non-significant trend toward decrease, while ghrelin levels did not change
      at all. CONCLUSIONS: The results of the present study in a unique experimental
      human model of maximal exposure to altitude and physical exercise demonstrate
      that extreme HA and strenuous physical exercise are coupled with specific
      endocrine adaptations. These include increased activity of the GH/IGF-I axis and
      a low T(3) syndrome but no change in ghrelin and leptin that was expected taking
      into account body weight decrease. These findings would contribute to better
      understanding human endocrine and metabolic physiology in hypoxic conditions.

PMID- 18057381
TI  - Insulin gene variable number of tandem repeats is not associated with weight from
      fetal life until infancy: the Generation R Study.
AB  - OBJECTIVE: The aim of this study was to examine whether the insulin gene variable
      number of tandem repeats (INS VNTR) is associated with growth patterns in fetal
      life and infancy. DESIGN AND METHODS: This study was embedded in the Generation R
      Study, a population-based prospective cohort study from fetal life until young
      adulthood. Fetal growth was assessed by ultrasounds in early, mid-, and late
      pregnancy. Anthropometry in infancy was assessed at birth and at the ages of 6
      weeks, 6 months, and 14 months. DNA for genotyping of the INS VNTR promoter
      region was available in 859 children. RESULTS: The genotype distribution was I/I
      50.8%, I/III 40.0%, and III/III 9.2%. III/III individuals had a shorter
      gestational age (P<0.005 versus I/I) and a lower birth weight (P<0.05 versus
      I/I). There were no differences in birth weight after adjusting for gestational
      age. Class III homozygotes had a smaller abdominal circumference/head
      circumference (HC) ratio (P<0.005 versus I/I) in mid-pregnancy, but not in late
      pregnancy. Also, III/III subjects had a relative decrease in HC (SDS) from mid
      pregnancy to the age of 14 months (P<0.05 versus I/I). No other differences in
      pre- and postnatal growth characteristics and patterns were found. CONCLUSIONS:
      Class III homozygotes were born at an earlier gestational age. No association was
      found between INS VNTR and birth weight adjusted for gestational age. Our data
      suggest that the III/III genotype may be associated with asymmetrical growth in
      mid-pregnancy, but not in late pregnancy.

PMID- 18057382
TI  - Reference range of serum calcitonin levels in humans: influence of calcitonin
      assays, sex, age, and cigarette smoking.
AB  - OBJECTIVE: The objective of this study was to re-evaluate the adult C(T)
      reference values determined by five different immunoassays and by introducing
      criteria for selecting control subjects. DESIGN: A prospective multicenter study.
      PATIENTS: Three hundred and seventy-five clinically euthyroid subjects. METHODS:
      We used five different C(T) immunoassays. Sera were assayed for the concentration
      of TSH, gastrin, procalcitonin, urea, calcium, and anti-thyroperoxidase
      antibodies. RESULTS: Screening for the various potential causes of
      hypercalcitoninemia led to the exclusion of 23% of the sera. Our reference value
      analysis dealt with 287 subjects (142 men and 145 women). The proportion of
      samples in which no C(T) was detected varied from 56% (for assay D) to 88% (for
      assay C). We observed significant correlations (whose magnitude depended on the
      assay used) between C(T) levels and age or body mass index (BMI) (primarily in
      men). The distribution of C(T) levels showed that 4.7, 9.8, 2.5, 6.5, and 8.0% of
      the values were over 10 pg/ml respectively. These values corresponded essentially
      to samples from 11 male subjects (median age: 55 years), most of whom were
      smokers. The highest C(T) values were around twice as high in men than women, and
      were higher in smokers than non-smokers. Conclusion In clinical practice (and
      after having excluded the usual causes of raised C(T) levels), the interpretation
      of C(T) assay results must take into account i) the method used; ii) the
      patient's gender, age, and weight; and iii) the potential influence of cigarette
      smoking.

PMID- 18057383
TI  - Analysis of extended human leukocyte antigen haplotype association with Addison's
      disease in three populations.
AB  - OBJECTIVE: Addison's disease is an organ-specific autoimmune disorder with a
      polygenic background. The aim of the study was to identify non-class II human
      leukocyte antigen (HLA) susceptibility genes for Addison's disease. DESIGN AND
      METHODS: Addison's disease patients from three European populations were analysed
      for selected HLA-DR-DQ alleles and for 11 microsatellite markers covering
      approximately 4 Mb over the HLA region. Subjects were 69 patients with Addison's
      disease from Estonia (24), Finland (14) and Russia (31). Consecutively recruited
      healthy newborns from the same geographical regions were used as controls (269
      Estonian, 1000 Finnish and 413 Russian). Association measures for HLA-DRB1, DQB1,
      DQA1 and 11 microsatellites between D6S273 and D6S2223 were taken. A low
      resolution full-house typing was used for HLA class II genes, while
      microsatellite markers were studied using fluorescence-based DNA fragment sizing
      technology. RESULTS: We confirmed that the HLA-DR3-DQ2 and the DQB1*0302
      DRB1*0404 haplotypes confer disease susceptibility. In Russian patients, we also
      found an increase of DRB1*0403 allele, combined with DQB1*0305 allele in three
      out of six cases (P<0.0001). Analysis of 11 microsatellite markers including STR
      MICA confirmed the strong linkage in DR3-DQ2 haplotypes but DRB1*0404-DQB1*0302
      haplotypes were diverse. MICA5.1 allele was found in 22 out of 24 Estonian
      patients, but results from Finnish and Russian patients did not support its
      independent role in disease susceptibility. CONCLUSION: HLA-DRB1*0403 was
      identified as a novel susceptibility allele for Addison's disease. Additionally,
      we found no evidence of a non-class II HLA disease susceptibility locus; however,
      the HLA-DR3-DQ2 haplotype appeared more conserved in patient groups with high DR
      DQ2 frequencies.

PMID- 18057384
TI  - Plasma ghrelin concentrations in type 1 diabetic patients with autoimmune
      atrophic gastritis.
AB  - OBJECTIVE: Type 1 diabetes mellitus patients (DM1) show increased prevalence of
      pernicious anaemia, the histological substrate of which is type A chronic
      atrophic gastritis (CAG) in the stomach corpus, the main source of ghrelin. We
      aimed to compare plasma ghrelin concentrations in DM1 patients with type A CAG
      (DM1-CAG), DM1 patients without type A CAG and healthy controls and in DM1-CAG
      group, to ascertain a possible relationship between ghrelin and biochemical
      markers of gastric mucosa atrophy and/or neuroendocrine (NE) cell hyperplasia and
      histological gastric biopsy findings. DESIGN AND METHODS: Fifteen DM1-CAG
      patients were matched for age, sex and body mass index with 15 DM1 patients
      without type A CAG and 15 controls. Pepsinogen I, pepsinogen II, gastrin,
      parietal cell antibodies, chromogranin A (CgA) and ghrelin were determined in all
      subjects. In DM1-CAG patients, immunohistochemical analysis of gastric biopsies
      using antibodies to CgA and ghrelin was performed. RESULTS: Ghrelin
      concentrations differed among groups; however, paired comparisons between groups
      were not significant. In DM1-CAG, no correlation was found between ghrelin and
      gastric body atrophy markers, pepsinogen I and the pepsinogen I/II ratio.
      Immunohistochemical studies of DMI-CAG patients showed CgA staining in 12 and
      ghrelin staining in 6, which was confined to the foci of NE cell hyperplasia.
      Those patients who stained positive for ghrelin had higher ghrelin concentrations
      when compared with the negative patients. CONCLUSIONS: Ghrelin concentrations are
      not decreased in DM1-CAG patients; thus, our data suggest that ghrelin is not a
      good marker of gastric mucosa atrophy in these patients, given the possible
      ghrelin synthesis in hyperplastic gastric endocrine/enterochromaffin-like cells.

PMID- 18057385
TI  - Food-dependent Cushing's syndrome: from molecular characterization to
      therapeutical results.
AB  - OBJECTIVE: Cortisol secretion in ACTH-independent macronodular adrenal
      hyperplasia (AIMAH) may be regulated by the aberrant expression of several G
      protein-coupled receptors. Bilateral adrenalectomy is the treatment of choice in
      most cases. We searched for aberrant receptor expression in a patient with AIMAH
      and evaluated the response to medical and surgical treatment. PATIENT: A 35-year
      old woman with amenorrhea, hirsutism, and hypertension presented ACTH-independent
      cortisol secretion with high androgen levels. Abdominal computed tomography
      showed bilateral adrenal macronodules (4.5 cm right and 1.0 cm left).
      Scintigraphy with I(131)-norcholesterol showed bilateral uptake, prevalent on the
      right side. Several in vivo stimulation tests were assessed before and after
      treatment and in vitro studies were performed after unilateral adrenalectomy.
      RESULTS: Plasma cortisol increased after a standard meal test (60%) and oral
      glucose loading (147%), and the response was blunted by pretreatment with 100
      microg s.c. octreotide. The therapy with long-acting release octreotide
      (octreotide-LAR) showed an improvement in urinary free cortisol (UFC) levels.
      Unilateral adrenalectomy was performed and histopathology revealed macronodular
      AIMAH. Cortisol and androgens increased after perifusion of tumoral tissue with
      glucose-dependent insulinotropic polypeptide (GIP), and GIP and LH-receptor
      overexpression was found in both the adrenal nodules and the adjacent cortex.
      After surgery, UFC and androgen levels normalized followed by clinical
      improvement. CONCLUSIONS: GIP and LH-receptor expression may coexist in AIMAH,
      influencing the functional and morphological phenotype. Aberrant hormone receptor
      expression enables specific pharmacological treatment, but long-term studies are
      needed to evaluate its real efficacy. Unilateral adrenalectomy may be a safe
      initial option, particularly for asymmetric bilateral adrenal enlargements.

PMID- 18057386
TI  - A 'smart' type of Cushing's syndrome.
AB  - Cushing's syndrome results from lengthy and inappropriate exposure to excessive
      concentrations of either endogenous or exogenous glucocorticoids. This case
      report describes a patient with a novel type of Cushing's syndrome due to the use
      of party drugs. A 35-year-old woman had gained 8 kg body weight in 5 months and
      complained of anxiety. She showed a Cushing-like appearance and mild hypertension
      (blood pressure, BP 150/95 mmHg). She reported daily use of increasing doses of
      gamma-hydroxybutyric acid (GHB), a popular party drug. ACTH plasma levels were in
      the upper normal range (41 ng/l), with normal plasma cortisol (0.36 micromol/l).
      She showed an abnormal overnight 1 mg dexamethasone suppression test (cortisol
      0.38 micromol/l). The urinary excretion of free cortisol in 24 h was also
      increased (0.47 micromol/24 h). CT scanning of the abdomen showed normal
      adrenals. After stopping GHB intake she lost 7 kg body weight and her BP
      normalized (BP 135/80 mmHg). GHB is a popular party drug in the Netherlands, but
      it is also used as a narcotic and for the treatment of narcolepsy. We hypothesize
      that GHB may bind to the pituitary gland gamma-aminobutyric acid-B receptors
      leading to ACTH overproduction.

PMID- 18057387
TI  - Novel BSCL2 gene mutation E189X in Chinese congenital generalized lipodystrophy
      child with early onset diabetes mellitus.
AB  - CONTEXT: Congenital generalized lipodystrophy (CGL) is a rare and heterogeneous
      disease of autosomal recessive inheritance. Until now, no genetic findings had
      been reported in Chinese patients with CGL. OBJECTIVE: To analyze Berardinelli
      Seip congenital lipodystrophy type 2 (BSCL2) and 1-acylglycerol-3-phosphate O
      acyltransferase 2 (AGPAT2) gene variation in a Chinese boy with CGL and his
      family. DESIGN, SETTING, AND PARTICIPANTS: All exons of BSCL2 and AGPAT2 with
      adjacent intron-exon junctions were analyzed using direct sequencing. MAIN
      OUTCOME MEASURES: Sequences of each exon and nearby intron of the BSCL2 and
      AGPAT2 genes of the family members were compared with the gene bank genomic
      sequences. RESULTS: DNA sequence analysis of the entire coding regions and
      surrounding uncoding regions disclosed a novel homozygous G-->T mutation at
      nucleotide 909 in exon 5 of the BSCL2 gene in the affected child. A heterozygous
      state of the G-->T mutation of the BSCL2 gene was also found in other family
      members. This mutation predicts the substitution of glutamic acid at codon 189 by
      the stop codon (Glu189X or E189X). No variation was found in the AGPAT2 gene.
      Conclusion E189X is a novel BSCL2 gene mutation that contributes to CGL formation
      in a family of Chinese origin.

PMID- 18057388
TI  - Quality of life is decreased in female patients treated for microprolactinoma.

PMID- 18057389
TI  - Unawareness of illness in neuropsychiatric disorders: phenomenological certainty
      versus etiopathogenic vagueness.
AB  - Awareness of illness is a form of self-knowledge concerning information about the
      pathological state, its functional consequence, and the way it affects the
      patient and his interaction with the environment. Unawareness of illness has
      raised much interest for its consequences on compliance with treatment,
      prognosis, and the patient's quality of life. This review highlights the great
      complexity of this phenomenon both at phenomenological and etiopathogenic levels
      in stroke, traumatic brain injury, psychosis, dementias, and mood disorders. In
      particular, the clinical expression is characterized by failure to acknowledge
      being ill, misattribution of symptoms, and noncompliance with treatment.
      Unawareness of illness may also be linked with characteristics that are peculiar
      to each individual disturbance, such as symptom duration and cognitive
      impairment. Despite a long-lasting interest in the clinical characteristics of
      unawareness, only recently has the focus of research investigated pathogenic
      mechanisms, with sometimes controversial results. The vast majority of studies
      have pointed out a remarkable involvement of the right hemisphere. Specifically,
      functional and structural changes of the dorso-lateral prefrontal cortex and some
      other frontal areas have often been found to be associated with awareness
      deficit, as well as parieto-temporal areas and the thalamus, although to a lesser
      extent. These data indicate the present difficulty of localizing a specific
      cerebral area involved in unawareness and suggest the existence of possible brain
      circuits responsible for awareness. In conclusion, phenomenological
      manifestations of poor awareness are well outlined in their complexity, whereas
      neuroanatomic and neuropsychological findings are still too vague and sparse and
      need further, greater efforts to be clarified.

PMID- 18057390
TI  - Effect of posterior cruciate ligament deficiency on in vivo translation and
      rotation of the knee during weightbearing flexion.
AB  - BACKGROUND: The effect of posterior cruciate ligament (PCL) deficiency on 6
      degrees of freedom in vivo knee-joint kinematics is unclear. HYPOTHESIS: In
      addition to constraining anterior-posterior translation, the PCL also functions
      to constrain the medial-lateral translation and rotation of the knee during
      weightbearing flexion of the knee. STUDY DESIGN: Controlled laboratory study.
      METHODS: Eight patients with a PCL injury in 1 knee and the other intact were
      scanned with magnetic resonance imaging, and 3-dimensional models of the femur
      and tibia were created for both knees. Each knee was imaged during quasistatic
      weight-bearing flexion (from 0 degrees to 105 degrees ) using a dual-orthogonal
      fluoroscopic system. The translation and rotation of the PCL-deficient knee were
      compared with the intact contralateral control. RESULTS: Posterior cruciate
      ligament deficiency caused an increase in posterior tibial translation beyond 30
      degrees of flexion compared with the intact contralateral knees. At 90 degrees of
      flexion, PCL deficiency increased posterior tibial translation by 3.5 mm (P <
      .05). In the medial-lateral direction, PCL deficiency resulted in a 1.1 mm
      increase in lateral tibial translation at 90 degrees of flexion (P < .05). With
      regard to rotation, PCL deficiency caused a significantly lower varus rotation
      (on average, 0.6 degrees lower) at 90 degrees of flexion. Posterior cruciate
      ligament deficiency caused a decreased internal tibial rotation throughout the
      range of flexion, but no significant difference was detected. CONCLUSIONS: This
      study quantitatively describes the effect of PCL injury on 6 degrees of freedom
      kinematics of the knee during quasistatic weightbearing flexion. Using the intact
      contralateral side as a control, we found that PCL injuries not only affect
      anterior-posterior tibial translation but also medial-lateral translation and
      rotation of the knee. CLINICAL RELEVANCE: These data provide baseline knowledge
      of the in vivo kinematics of the knee after PCL injury. Surgical reconstruction
      of the injured PCL, either using single-bundle or double-bundle technique, should
      not only focus on restoration of posterior stability of the knee but also the
      medial-lateral stability as well as the rotational stability. These findings may
      help to explain the long-term degenerative changes seen in PCL-deficient knees.

PMID- 18057391
TI  - Back to the future? Active learning of medical physiology in the 1900s.
AB  - In the early 1900s, teachers of medical physiology faced a problem familiar to
      those teaching the subject in a contemporary setting: too much information, too
      little time, too many students in crowded rooms, and exams that discouraged real
      learning. They wanted students to question authority and demand evidence and thus
      be better prepared for medicine. Their solution was to bring students into
      laboratories and minimize didactic learning as they felt strongly that useful
      information could not be obtained merely from books. Thus, they were strong
      proponents of what we now call active learning.

PMID- 18057392
TI  - From a pump handle to oral rehydration therapy: a model of translational
      research.
AB  - Few afflictions have attracted as much attention and impacted on as many societal
      and biomedical areas as cholera. Dr. John Snow's studies launched the field of
      epidemiology, were early applications of medical cartography, and promoted the
      use of statistical methods in medicine. The finding that cholera was due to the
      ingestion of contaminated water lent to the demise of the prevalent "miasmatic
      theory of contagion," set the platform for the "germ theory of disease," and
      promoted the growth of public health concerns for water purification and
      sanitation. More recent attention to this disease led to the notion of "secretory
      diarrhea" and the translation of basic principles to the development of oral
      rehydration therapy and its "spin-offs" (Gatorade and Pedilyte).

PMID- 18057394
TI  - Guidelines for reporting statistics in journals published by the American
      Physiological Society: the sequel.

PMID- 18057395
TI  - The need for accurate statistical reporting. A commentary on "Guidelines for
      reporting statistics in journals published by the American Physiological Society:
      the sequel".

PMID- 18057396
TI  - Statistics: not a confidence trick. A commentary on "Guidelines for reporting
      statistics in journals published by the American Physiological Society: the
      sequel".

PMID- 18057397
TI  - How should we achieve high-quality reporting of statistics in scientific
      journals? A commentary on "Guidelines for reporting statistics in journals
      published by the American Physiological Society".

PMID- 18057398
TI  - Sustained efforts should promote statistics literacy in physiology. Commentary on
      "Guidelines for reporting statistics in journals published by the American
      Physiological Society: the sequel".

PMID- 18057401
TI  - Claude Bernard Distinguished Lecture. Becoming a truly helpful teacher:
      considerably more challenging, and potentially more fun, than merely doing
      business as usual.
AB  - Few medical faculty members are adequately prepared for their instructional
      responsibilities. Our educational traditions were established before we had
      research-based understandings of the teaching-learning process and before brain
      research began informing our understandings of how humans achieve lasting
      learning. Yet, there are several advantages you may have. If your expertise is at
      one of the frontiers of human biology, your teaching can be inherently
      fascinating to aspiring health professionals. If your work has implications for
      human health, you have another potential basis for engaging future clinicians.
      And, thanks to Claude Bernard's influence, you likely are "process oriented," a
      necessary mindset for being an effective teacher. There are also challenges you
      may face. Your medical students will mostly become clinicians. Unless you can
      help them see connections between your offerings and their future work, you may
      not capture and sustain their interest. To be effective, teachers, like
      clinicians, need to be interactive, make on-the-spot decisions, and be "emotional
      literate." If you aren't comfortable with these demands, you may have work to do
      toward becoming a truly helpful teacher. Program changes may be needed. Might
      your program need to change 1) from being adversarial and controlling to being
      supportive and trust based or 2) from mainly dispensing information to mainly
      asking and inviting questions? In conclusion, making changes toward becoming a
      truly helpful teacher can bring benefits to your students while increasing your
      sense of satisfaction and fulfillment as a teacher. If you choose to change, be
      gentle with yourself, as you should be when expecting your students to make
      important changes.

PMID- 18057402
TI  - Using a classic paper by I. E. Lawton and N. B. Schwartz to consider the array of
      factors that control luteinizing hormone production.
AB  - Two significant benefits derived from reading and discussing classic scientific
      papers in undergraduate biology courses are 1) providing students with the
      realistic perspective that science is an ongoing process (rather than a set of
      inarguable facts) and 2) deepening the students' understanding of physiological
      processes. A classic paper that is useful in both of these regards is by I. E.
      Lawton and N. B. Schwartz (A circadian rhythm of luteinizing hormone secretion in
      ovariectomized rats. Am J Physiol 214: 213-217, 1968). The primary objective of
      the study is to determine whether tonic (pulsatile) secretion of luteinizing
      hormone (LH) from the pituitary gland exhibits a circadian rhythm. While this
      hypothesis seems relatively straightforward, its in vivo investigation
      necessitates an awareness of the multitude of factors, in addition to the
      circadian clock, that can influence plasma LH levels (and a consideration of how
      to control for these factors in the experimental design). Furthermore, discussion
      of the historical context in which the study was conducted (i.e., before the
      pulsatile nature of LH secretion had been discovered) provides students with the
      realistic perspective that science is not a set of facts but rather a systematic
      series of attempts by scientists to understand reality (a perspective that is
      difficult to convey using a traditional textbook alone). A review of the
      historical context in which the study was conducted, and a series of discovery
      learning questions are included to facilitate classroom discussions and to help
      deepen students' understanding of the complex nature of pituitary hormone
      regulation.

PMID- 18057403
TI  - Career counseling: 101+ things you can do with a degree in biology.
AB  - Biology is the science of life and of how living things work. Our students choose
      to major in biology in college because of a fascination with understanding how
      living things function, but often they have difficulty in identifying a career
      that uses their foundation in biology despite the variety of biology-based
      careers available. The purpose of this discussion is to assist biology students
      and the career counselors who work with them in identifying satisfying careers
      that build upon their interest and foundation in biology. The categories of
      career options include research, healthcare, teaching, science writing,
      administration/management, government, industry, and miscellaneous careers that
      do not fit into the other categories.

PMID- 18057404
TI  - Translating symptoms into mechanisms: functional GI disorders.
AB  - Functional gastrointestinal disorders are the most common problem in
      gastroenterological practice. They are defined by chronic abdominal symptom
      complexes that occur in the absence of underlying structural abnormalities. The
      pathogenesis of these disorders is heterogeneous and involves behavioral,
      infective, and inflammatory components. Common symptoms are abdominal pain,
      diarrhea, constipation, and bloating. Mechanisms underlying these symptoms
      include alterations in gastrointestinal motility, visceral perception, altered
      epithelial function, and disturbances in fermentation activity by gut commensal
      bacteria.

PMID- 18057405
TI  - Influence of caffeine ingestion on perceived mood states, concentration, and
      arousal levels during a 75-min university lecture.
AB  - This investigation aimed to assess the effect of a caffeine supplement on
      perceived mood state, concentration, and arousal during a 75-min university
      lecture. Methods. This randomized, blind, cross-over design investigation ran
      over a course of 2 consecutive weeks. During week 1, 10 third-year Human Movement
      and Exercise Science students were assigned to either a caffeine- or placebo
      supplemented group and were subsequently required to attend a 75-min exercise
      rehabilitation lecture. Seven days later, students were assigned to the opposite
      supplementation group before attending a second follow-on lecture, equal in
      duration to that of week 1. At the conclusion of each lecture, students were
      required to complete a mood perception questionnaire to assess the perceived
      level of mood state, concentration, and arousal during the lecture. The results
      showed that after caffeine consumption, students perceived themselves to be
      significantly more awake, clear minded, energetic, alert, and anxious (P < 0.05).
      Additionally, students also felt they were better able to concentrate and had a
      greater level of arousal than when the placebo was consumed (P < 0.05). In
      conclusion, the results of this investigation show that university students
      report enhanced perceptual feelings of behavior and mood state when a low dose of
      caffeine is consumed 60 min prior to a 75-min academic lecture.

PMID- 18057406
TI  - Does gender influence learning style preferences of first-year medical students?
AB  - Students have specific learning style preferences, and these preferences may be
      different between male and female students. Understanding a student's learning
      style preference is an important consideration when designing classroom
      instruction. Therefore, we administered the visual, auditory, reading/writing,
      kinesthetic (VARK) learning preferences questionnaire to our first-year medical
      students; 38.8% (97 of 250 students) of the students returned the completed
      questionnaire. Both male (56.1%) and female (56.7%) students preferred multiple
      modes of information presentation, and the numbers and types of modality
      combinations were not significantly different between genders. Although not
      significantly different, the female student population tended to be more diverse
      than the male population, encompassing a broader range of sensory modality
      combinations within their preference profiles. Instructors need to be cognizant
      of these differences and broaden their range of presentation styles accordingly.

PMID- 18057407
TI  - Pros and cons of a group webpage design project in a freshman anatomy and
      physiology course.
AB  - To generate motivation and promote the development of written communication
      skills, students in a freshman-level anatomy and physiology course for nonmajors
      created group webpages describing historically important diseases. After the
      groups had been formed, each individual was assigned specific components of the
      disease (e.g., causes or treatments), which were subsequently combined into a
      final product. Interviews and questionnaires were used to document students'
      previous educational experiences regarding, and attitudes toward, the project.
      Students learned more about website design than about anatomy and physiology, but
      students preferred the assignment over traditional term papers. Although most
      students could find relevant information for this project on the internet, they
      were uncritical in judging the accuracy of the information they found.

PMID- 18057408
TI  - Practical application of fundamental concepts in exercise physiology.
AB  - The collection of primary data in laboratory classes enhances undergraduate
      practical and critical thinking skills. The present article describes the use of
      a lecture program, running in parallel with a series of linked practical classes,
      that emphasizes classical or standard concepts in exercise physiology. The
      academic and practical program ran under the title of a particular year II module
      named Sports Performance: Physiology and Assessment, and results are presented
      over a 3-yr period (2004-2006), based on an undergraduate population of 31 men
      and 34 women. The module compared laboratory-based indexes of endurance (e.g.,
      ventilatory threshold and exercise economy) and high-intensity exercise (e.g.,
      anaerobic power), respectively, with measures of human performance (based on 20-m
      shuttle run tests). The specific experimental protocols reinforced the lecture
      content to improve student understanding of the physiological and metabolic
      responses (and later adaptations) to exercise. In the present study, the
      strongest relationship with endurance performance was the treadmill velocity at
      maximal aerobic power (r = +0.88, P < 0.01, n = 51); in contrast, the strongest
      relationship with high-intensity exercise performance was the mean power output
      (in W/kg) measured during a 30-s all-out cycle ergometer sprint (r = +0.80, P <
      0.01, n = 48). In class student data analysis improved undergraduate indepth or
      critical thinking during seminars and enhanced computer and data presentation
      skills. The endurance-based laboratories are particularly useful for examining
      the underlying scientific principles that determine aerobic performance but could
      equally well be adapted to investigate other topics, e.g., differences in the
      exercise response between men and women.

PMID- 18057409
TI  - Vertebrate osmoregulation: a student laboratory exercise using teleost fish.
AB  - Here, we describe a laboratory experiment as part of an upper-level vertebrate
      physiology course for biology majors to investigate the physiological response of
      vertebrates to osmoregulatory challenges. The experiment involves measuring
      plasma osmolality and Na+-K+-ATPase activity in gill tissue of teleost fish
      acclimated to water of differing salinity. We describe results obtained using the
      widely available goldfish (Carassius auratus) and a common baitfish, the Gulf
      killifish (Fundulus grandis). The procedures described are generally applicable
      to other fish species, and they provide an alternative to the experimental use of
      humans or other mammalian species to investigate osmoregulation mechanisms. In
      addition to reenforcing the conceptual material covered in lecture, this
      laboratory exercise trains students in a wide range of laboratory and analytical
      skills, such as calculating and performing dilutions, pipetting, tissue sampling
      and homogenizing, preparing standard curves, conducting enzymatic assays, and
      analyzing and interpreting results. Typical student results are presented and
      discussed, as are common experimental and conceptual mistakes made by students.

PMID- 18057410
TI  - Fish on Prozac: a simple, noninvasive physiology laboratory investigating the
      mechanisms of aggressive behavior in Betta splendens.
AB  - The neuromodulator serotonin is an important regulator of aggressive behavior in
      vertebrates. Experimentally increasing synaptic levels of serotonin with
      fluoxetine, a selective serotonin reuptake inhibitor, has been shown to reliably
      decrease the expression of aggressive behavior. Here, we describe a method by
      which fluoxetine can be noninvasively administered to male Betta splendens (an
      attractive model for the study of aggressive behavior) and describe a simple
      laboratory exercise that allows students to experimentally investigate the
      physiological mechanisms of aggressive behavior. We demonstrate that relatively
      short-term exposure (3 h) of male bettas to as little as 3 microg/ml of
      fluoxetine-treated aquarium water is sufficient to reduce the expression of
      specific aggressive behaviors. We emphasize the physiological concepts that can
      be addressed with this exercise, including the role of the serotonergic system in
      regulating aggression, and the interplay of environmental contaminants and
      physiology in regulating the expression of behavior. We also highlight important
      aspects of experimental design. This exercise can be flexibly altered to
      accommodate one or several laboratory periods. It is also low cost, is low impact
      to the animals, and requires minimal preparation time for instructors.

PMID- 18057411
TI  - Students' conceptions of underlying principles in medical physiology: an
      interview study of medical students' understanding in a PBL curriculum.
AB  - Medical physiology is known to be a complex area where students develop
      significant errors in conceptual understanding. Students' knowledge is often
      bound to situational descriptions rather than underlying principles. This study
      explores how medical students discern and process underlying principles in
      physiology. Indepth interviews, where students elaborated on principles related
      to blood pressure and blood pressure regulation, were carried out with 16 medical
      students in a problem-based learning curriculum. A qualitative, phenomenographic
      approach was used, and interviews were audiotaped, transcribed, qualitatively
      analyzed, and categorized. Four categories were outlined. The underlying
      principles were conceived as follows: 1) general conditions for body function at
      a specified time point, 2) transferable phenomena between organ systems and time
      points, 3) conditionally transferable phenomena between organ systems and time
      points, and 4) cognitive constructions of limited value in medical physiology.
      The results offers insights into students' thinking about underlying principles
      in physiology and suggest how understanding can be challenged to stimulate deep
      level processing of underlying principles rather than situational descriptions of
      physiology. A complex conception of underlying principles includes an ability to
      problemize phenomena beyond long causal reasoning chains, which is often rewarded
      in traditional examinations and tests. Keywords for problemized processing are as
      follows: comparisons, differences, similarities, conditions, context, relevance,
      multiple sampling, connections, and dependencies.

PMID- 18057413
TI  - How does conjugated bilirubin appear in the bloodstream?

PMID- 18057414
TI  - A trend toward improved learning of cardiovascular pathophysiology in medical
      students from using a human patient simulator: results of a pilot study.

PMID- 18057415
TI  - The ''perfect teacher'' and the story of his ''zero defects'' project.

PMID- 18057416
TI  - Scientific principles of education research: Experimental Biology 2007.

PMID- 18057417
TI  - Effective use of course management systems to enhance student learning:
      Experimental Biology 2007.
AB  - Course management systems are software packages that support teaching and
      learning by providing web-based tools, services, and resources. Electronic course
      management can facilitate course organization, teaching delivery, communication,
      collaboration, and assessment. This article reports on a symposium on the use of
      course management systems, presented by the Teaching of Physiology Section of the
      American Physiological Society, at the Experimental Biology Meeting of 2007.

PMID- 18057418
TI  - APS undergraduate brainstorming summit report.

PMID- 18057419
TI  - Beijing declaration on medical pathophysiology education.

PMID- 18057420
TI  - Conceptual assessment in the biological sciences: a National Science Foundation
      sponsored workshop.
AB  - Twenty-one biology teachers from a variety of disciplines (genetics, ecology,
      physiology, biochemistry, etc.) met at the University of Colorado to begin
      discussions about approaches to assessing students' conceptual understanding of
      biology. We considered what is meant by a "concept" in biology, what the
      important biological concepts might be, and how to go about developing assessment
      items about these concepts. We also began the task of creating a community of
      biologists interested in facilitating meaningful learning in biology. Input from
      the physiology education community is essential in the process of developing
      conceptual assessments for physiology.

PMID- 18057422
TI  - Vascular structure and function in chronic obstructive pulmonary disease: a
      chicken and egg issue?

PMID- 18057423
TI  - Of contagion and inherited susceptibility: an epidemiologic tribute to George W.
      Comstock.

PMID- 18057424
TI  - Notes from the NHLBI director: shaping the future of research--the NHLBI
      strategic plan.

PMID- 18057425
TI  - Atypical coverage for community-acquired pneumonia.

PMID- 18057426
TI  - Proton pump inhibitors are not antacids!

PMID- 18057427
TI  - Euthanasia and physician-assisted suicide: ongoing controversies.

PMID- 18057428
TI  - The prevalence of cardiovascular risk factors in male patients who have lower
      urinary tract symptoms.
AB  - OBJECTIVES: To assess the prevalence of cardiovascular risk factors in men
      presenting with lower urinary tract symptoms, and their possible correlation with
      the severity of such symptoms. DESIGN: Retrospective cohort study. SETTING:
      Specialty clinic, Hong Kong. PATIENTS: A total of 617 men presenting with lower
      urinary tract symptoms between April 2005 and October 2006. MAIN OUTCOME
      MEASURES: Presence of cardiovascular risk factors inferred from the prior and
      current medical and social history as well as physical examination and
      investigative findings, among patients with International Prostatic Symptom
      Scores of different severity. RESULTS: Of 617 patients, 268 (43%) had known
      hypertension and 318 (52%) had a history of smoking. According to the World
      Health Organization criteria for Asian populations, 396 (64%) patients were
      considered to be overweight (body mass index > or =23 kg/m(2)). A total of 178
      (29%) patients were either known to have or were diagnosed to have dysglycaemia
      during workup. For dyslipidaemia and hyperuricaemia, the corresponding figures
      were 331 (54%) and 191 (31%). In total, 264 (43%) patients were newly diagnosed
      as having dysglycaemia, dyslipidaemia, or hyperuricaemia. Logistic regression
      indicated that only hyperuricaemia and a smoking history were significant
      predictors of moderate-to-severe lower urinary tract symptoms (International
      Prostatic Symptom Score > or =8), with respective adjusted odds ratios of 2.20
      (95% confidence interval, 1.12-4.31; P=0.022) and 2.11 (1.24-3.57, P=0.006).
      Patients with moderate-to-severe International Prostatic Symptom Scores had a
      statistically higher chance of having at least one cardiovascular risk factor
      during assessment (P=0.001). CONCLUSIONS: Cardiovascular risk factors were
      prevalent in male patients who had lower urinary tract symptoms; a large portion
      of these cardiovascular risk factors were not recognised until their urological
      consultations. Patients with moderate-to-severe lower urinary tract symptoms
      (International Prostatic Symptom Score > or =8) had statistically higher chances
      of having more cardiovascular risk factors.

PMID- 18057429
TI  - Spontaneous fractures in nursing home residents.
AB  - OBJECTIVES: To evaluate spontaneous long bone fractures occurring in nursing home
      residents and to identify what factors put them at risk for fractures. DESIGN:
      Retrospective study. SETTING: Department of Orthopaedics and Traumatology of a
      pubic hospital in Hong Kong. PATIENTS: A total of 30 nursing home residents who
      developed spontaneous long bone fractures between 1994 and 2005 were reviewed.
      MAIN OUTCOME MEASURES: Demographic data, mechanism of injury, pattern of
      fractures, associated risk factors, complications, outcomes, and post-treatment
      status. RESULTS: The mean age of patients was 84 years. Co-morbidities were as
      follows: 22 patients were bedridden, 21 required long-term feeding by Ryle's
      tube, 19 had a history of cerebrovascular accident and 18 of whom had a long bone
      fracture on the side of the hemiplegia, 15 had dementia, and 25 had lower limb
      contractures. Closed supracondylar fractures of the femur occurred in 23
      patients, 17 of whom presented with limb deformity. In 21 patients, fractures
      were treated successfully with hinged braces. In one patient, the fracture
      changed from closed to open. In five patients, the fractures were complicated by
      sacrum or heel sores, and in one by infected nonunion. In 28 patients, the
      fractures eventually healed without further complications. Three formerly
      bedridden patients were able to sit after their fractures had been treated.
      CONCLUSIONS: Female nursing home residents who require long-term Ryle's tube
      feeding, have dementia, hemiplegia, lower limb contractures, osteoporosis, or are
      bedridden, are at high risk for spontaneous fractures.

PMID- 18057430
TI  - Dosing of proton pump inhibitors in a private hospital in Hong Kong.
AB  - OBJECTIVE: To study the prescribing pattern of proton pump inhibitors with regard
      to the time of dosing. DESIGN: Retrospective study. SETTING: Private hospital,
      Hong Kong. PATIENTS: All patients prescribed three specific proton pump
      inhibitors from 1 January to 31 July 2006 were included. MAIN OUTCOME MEASURES:
      For all three proton pump inhibitors, the prescribed dosing instructions were
      recorded as well as the specialties of the corresponding prescribers. RESULTS:
      The ratio of doctors prescribing proton pump inhibitors before meals versus at
      other times was 1:105. The ratio of patients receiving proton pump inhibitors
      before meals versus at other times was 1:341. The number of tablets of proton
      pump inhibitors prescribed before meals versus at other times was 1:409.
      CONCLUSIONS: The overwhelming majority of doctors in this study did not prescribe
      proton pump inhibitors before meals.

PMID- 18057431
TI  - The epidemiology and clinical characteristics of Crohn's disease in the Hong Kong
      Chinese population: experiences from a regional hospital.
AB  - OBJECTIVE: To study the descriptive epidemiology and clinical profile of patients
      with Crohn's disease. DESIGN: Retrospective study. SETTING: Regional hospital,
      Hong Kong. PATIENTS: Patients with Crohn's disease diagnosed between January 1991
      and December 2006 inclusive. RESULTS: Over the period studied, 27 Chinese
      patients were diagnosed with Crohn's disease in our hospital. Our hospital-based
      incidence and prevalence rate had increased more than 2- and 5-fold, respectively
      over that period. The mean age at diagnosis was 26 years and median duration of
      disease was 81 months. Most patients had ileocolonic disease (67%) followed by
      Crohn's colitis (22%) and ileal disease (11%); more patients had non-stricturing
      and non-penetrating disease (63%) than stricturing (15%) or penetrating disease
      (22%). Peri-anal disease occurred in 37% of our patients. At diagnosis, many of
      the patients (41%) had mild-moderate disease, but 30% each had moderate-severe
      and severe-fulminant disease. At the time of this study, 85% of the patients were
      in disease remission with medical treatment. However, 48% had undergone surgery
      for diagnosis or complications. No patient had developed colorectal cancer or
      died. CONCLUSIONS: The incidence and prevalence of Crohn's disease are increasing
      in the Chinese population. It usually affects young persons with a substantial
      proportion of patients presented with severe-fulminant disease. More
      epidemiological and clinical studies are needed for this emerging disease in
      Asian regions.

PMID- 18057432
TI  - Laparoscopic versus open hepatectomy for liver tumours: a case control study.
AB  - OBJECTIVE: To evaluate the benefits of laparoscopic versus open resection of
      liver tumours. DESIGN: Case control study. SETTING: Tertiary teaching hospital,
      Hong Kong. PATIENTS: Data from 25 patients who underwent laparoscopic resections
      for liver tumours from 2003 to 2006 were compared to a retrospective series of 25
      patients who underwent open hepatectomy in a pair-matched design. MAIN OUTCOME
      MEASURES: Duration of operation, operative morbidity and mortality, blood loss,
      tumour resection margin, analgesics usage, days to return to an oral diet,
      duration of postoperative hospital stay, and survival of patients with
      malignancy. RESULTS: The demographic data and the tumour characteristics were
      comparable in the two patient groups, as were mortality (0% in both groups) and
      morbidity rates (4% in both groups). Two (8%) of the patients having laparoscopic
      resections were converted to open surgery. There was no statistically significant
      difference between the two groups in terms of operating time or resection
      margins. However, the laparoscopically treated patients experienced significantly
      less blood loss (median, 100 vs 250 mL), had shorter hospital stays (median, 4 vs
      7 days), were prescribed less analgesia (median morphine dosage, 0.16 vs 0.83 mg
      per kg body weight), and resumed oral diet earlier (median, 1 vs 2 days). For
      patients with malignant tumours, there was no significant difference between the
      two groups in terms of actuarial and disease-free survival. CONCLUSION: Compared
      to open hepatectomy, in selected patients laparoscopic liver resection delivers
      the benefits of decreased blood loss, shorter hospital stay, lesser requirement
      for analgesics, and an earlier return to an oral diet, without evidence of
      compromised oncological clearance.

PMID- 18057433
TI  - Bleeding pseudoaneurysms complicating upper abdominal surgery.
AB  - OBJECTIVE: To review the management of ruptured pseudoaneurysms following upper
      abdominal surgery. DESIGN: Retrospective study. SETTING: Minimal access surgery
      centre, Hong Kong. PATIENTS: Patients who were diagnosed to have a pseudoaneurysm
      after undergoing major upper abdominal surgery were recruited during the period
      of 1998 to 2006. MAIN OUTCOME MEASURES: Success rate of haemostasis, re-bleeding
      rate, re-intervention rate, and mortality. RESULTS: During the study period, a
      total of eight patients (median age, 61 years) were managed in our department for
      bleeding pseudoaneurysms following cholecystectomy, gastrectomy, or Whipple's
      operation. Five patients underwent upper endoscopy as the initial investigation.
      In four of these five patients, visceral artery pseudoaneurysms were identified
      by angiography and haemostasis was achieved without re-bleeding. The one for whom
      angiographic identification of the bleeding source failed, was successfully
      treated subsequently by open plication. In three other patients, open surgical
      haemostasis was resorted to and achieved in two of them. However, one of the
      latter had re-bleeding, which was successfully treated by embolisation. The one
      who failed open identification of the bleeding source, was eventually also
      treated successfully by embolisation. The overall success rates of embolisation
      and open surgery were 80% and 67%, respectively, and the re-bleeding rates were
      0% and 33%, respectively. The corresponding mortality rates were 20% and 33%;
      both deaths were associated with multi-organ failure. There were no procedure
      related complications following embolisation. CONCLUSIONS: Based on our
      experience, visceral angiography can enable the diagnosis and treatment of
      ruptured pseudoaneurysm in a single session. The procedure is safe, the re
      bleeding rate is low, and it is as effective as alternative treatments, and
      should be considered a first-line intervention in patients with bleeding
      pseudoaneurysms complicating upper abdominal surgery.

PMID- 18057434
TI  - Identifying prognostic factors for survival in advanced cancer patients: a
      prospective study.
AB  - OBJECTIVE: To identify potential prognostic factors affecting the survival in
      patients with advanced cancer in a local palliative care unit. DESIGN:
      Prospective cohort study. SETTING: Palliative Care Unit of a regional hospital in
      Hong Kong. PATIENTS: All advanced cancer in-patients and out-patients who were
      enrolled into the palliative care service of the United Christian Hospital
      between January and December 2002 were recruited. MAIN OUTCOME MEASURES:
      Potential prognostic factors including demographic data, tumour characteristics,
      blood parameters, functional status, co-morbidities, total symptom score, and
      psychosocial parameters were recorded upon enrollment. RESULTS: A total of 170
      patients were eligible for analysis; their mean age was 69 (standard deviation,
      12) years, of which 106 (62%) were male. Overall median survival was 77
      (interquartile range, 31-160) days. The most frequent primary malignancy was lung
      (n=58, 34%), followed by liver (n= 24, 14%) and lower gastro-intestinal tract
      (n=24, 14%). By univariate analysis, 11 factors affected survival, including: age
      (P=0.040), number of metastatic sites involved (P=0.001), peritoneal metastases
      (P=0.009), skin metastases (P=0.011), tachycardia (P=0.009), serum albumin
      concentration (P<0.001), white cell count (P=0.002), Karnofsky Performance Status
      score (P<0.001), Hamilton Depression Scale score (P=0.004), Edmonton Symptom
      Assessment System score (P=0.003), and McGill Quality of Life (Hong Kong)-single
      item score (P=0.002). Multivariable Cox regression analysis revealed that only
      age (hazard ratio=0.84; 95% confidence interval, 0.73-0.96), number of metastatic
      sites involved (1.33; 1.13-1.56), serum albumin concentration (0.95; 0.92-0.98),
      Karnofsky Performance Status score (0.86; 0.78-0.96), and Edmonton Symptom
      Assessment System score (1.22; 1.05-1.41) were independent prognosticators.
      CONCLUSION: Age, number of involved metastatic sites, serum albumin, Karnofsky
      Performance Scale score, and Edmonton Symptom Assessment System score were
      independent prognosticators. Further studies are needed to provide a prognostic
      instrument applicable in local clinical settings.

PMID- 18057435
TI  - An update of treatment options for neovascular age-related macular degeneration.
AB  - OBJECTIVES: To review the role of conventional and new treatment modalities in
      the management of neovascular age-related macular degeneration. DATA SOURCES AND
      EXTRACTION: Literature search of Medline till March 2007, using the key
      words/terms 'treatment' and 'age-related macular degeneration' to retrieve
      relevant original papers and review articles. DATA SYNTHESIS: Age-related macular
      degeneration is the leading cause of irreversible visual loss in the elderly in
      developed countries. Neovascular age-related macular degeneration has a
      relentless course and the consequent visual loss is debilitating. Successful
      treatment has always been a challenge due to poor understanding of its
      pathogenesis. Laser photocoagulation and photodynamic therapy with verteporfin
      are the standard conventional treatments. However, these approaches do not
      prevent disease recurrence and repeated treatments are required. Recent advances
      in understanding the molecular pathway for the angiogenesis of neovascular age
      related macular degeneration enables exploration of new treatment approaches.
      Antiangiogenic therapy with anti-vascular endothelial growth factor agents, such
      as pegaptanib and ranibizumab, have recently been approved for clinical practice.
      Other antiangiogenic agents include bevacizumab, triamcinolone, and anecortave
      are also being evaluated in clinical trials. Additional treatment modalities
      include transpupillary thermotherapy and surgical intervention. CONCLUSIONS:
      Regarding patients with neovascular age-related macular degeneration, increased
      understanding in its pathogenesis coupled with rapid development in instrumental
      technology and new/emerging medications greatly expands available treatment
      options. Despite these various therapeutic options, current treatment is mainly
      directed at achieving visual stabilisation. Restoration of vision with newer
      agents is limited and not possible in every patient. Thus, early recognition and
      treatment to arrest the progression of neovascular age-related macular
      degeneration is the preferred means of attaining the best visual outcome.

PMID- 18057436
TI  - Lithium overdose causing non-convulsive status epilepticus--the importance of
      lithium levels and the electroencephalography in diagnosis.
AB  - We report a case of lithium overdose in a patient who presented in non-convulsive
      status epilepticus. The lithium toxicity was probably due to interaction with
      Moduretic. The diagnosis was not suspected until electroencephalography was
      performed. This case underscores the importance of therapeutic drug level
      monitoring of lithium, especially where toxicity is suspected, and the
      indispensable role electroencephalography plays by allowing a correct diagnosis
      to be made promptly.

PMID- 18057437
TI  - Perforation of the gall bladder following typhoid fever-induced ileal
      perforation.
AB  - Gall bladder perforation is a potentially life-threatening condition. Spontaneous
      perforation is infrequent and rarely seen in the absence of gallstones but gall
      bladder perforation is an occasional complication of typhoid fever. If such
      perforations are not treated in time, mortality rates are very high. We report a
      case of gall bladder perforation complicating typhoid fever following enteric
      perforation of the ileum necessitating sequential laparotomies during the same
      admission.

PMID- 18057438
TI  - Oesophageal gastro-intestinal stromal tumour presenting with rupture into pleural
      cavity.
AB  - Gastro-intestinal stromal tumours are rarely found in the oesophagus and it is
      uncommon for these tumours to present with rupture. In this paper, we report a
      case where the tumour ruptured through the distal oesophagus. As a result, the
      patient underwent surgical tumour dissection. A histopathological examination of
      the tumour mass confirmed that it was a gastro-intestinal stromal tumour. In this
      report, we review the diagnosis, pathology, and treatment of a patient presenting
      with a ruptured oesophageal gastro-intestinal stromal tumour.

PMID- 18057439
TI  - Squamous cell carcinoma arising from an epidermal cyst.
AB  - There are few case reports in the English literature concerning malignant
      transformation of an epidermal cyst into squamous cell carcinoma. We report a
      case of squamous cell carcinoma arising from a 40-year epidermal cyst in the
      proximal left thigh of a 74-year-old man. The epidermal cyst had increased in
      size in the previous 3 years. The patient presented with a discharge from the
      lesion. Ultrasonography and magnetic resonance imaging of the lesion suggested
      malignancy. An intra-operative frozen section of an incisional biopsy of the
      lesion found it to be an epidermal cyst with suspected malignant change, so a
      marginal excision of the lesion was performed. Squamous cell carcinoma arising
      from the epidermal cyst was confirmed histologically. A wide excision was done in
      order to obtain an adequate resection margin. A computed tomographic scan of the
      thorax and abdomen found no evidence of metastases. No evidence of recurrence was
      noted in the latest follow-up, 2 years postoperatively.

PMID- 18057440
TI  - Sequential non-traumatic femoral shaft fractures in a patient on long-term
      alendronate.
AB  - Fractures associated with osteoporosis are common among elderly people and
      postmenopausal women. Bisphosphonate is an effective anti-resorptive drug
      commonly used for the prevention and treatment of osteoporosis. There are,
      however, concerns about potential side-effects during long-term treatment with
      alendronate. We report a case where an 82-year-old woman who had been taking
      alendronate for 10 years presented with two episodes of non-traumatic femoral
      shaft fracture. An iliac bone biopsy showed severely suppressed bone turnover,
      suggestive of adynamic bone disease. We suspect the bone turnover suppression was
      related to the prolonged use of alendronate.

PMID- 18057441
TI  - Cutis marmorata telangiectatica congenita.

PMID- 18057442
TI  - The living will--pitfalls, benefits and a way forward.

PMID- 18057443
TI  - Porcelain spoon broken and swallowed during convulsion.

PMID- 18057444
TI  - Wound care organizations, programs, and certifications: an overview.
AB  - The number and variety of wound care organizations and certification programs
      have increased considerably in recent years. Many healthcare professionals
      interested in pursuing certification, employers who want to hire them, and the
      public at large are confused about the plethora of certification designations,
      program names, and requirements. Some of the largest wound care organizations in
      the US support or develop educational programs and meetings or support
      credentialing programs. Two of the four largest credentialing organizations are
      accredited. Information about the effect of credentialing on healthcare provider
      knowledge and clinical skills is not available and standards are needed to help
      healthcare providers and employers decide which program best serves their needs.
      Most importantly, research to ascertain the effects of educational programs and
      credentialing on patient outcomes must be conducted to help improve the quality
      of care and substantiate the goals of the credentialing programs.

PMID- 18057445
TI  - Controversies regarding vascular disease in the patient with diabetes: a review
      of the literature.
AB  - Vascular disease in the patient with diabetes represents a potentially
      devastating complication. Tri-neuropathy (sensory, motor, and autonomic) often
      predisposes patients to ulceration and vascular disease leads to delayed healing.
      Vascular pathology compromises blood flow and oxygen provision, affecting
      healing, infection, sepsis, amputation, and mortality. Recent research suggests
      that vascular reconstruction should not be withheld on the basis of arteriolar
      capillary involvement and while oxygen levels may provide important prognostic
      and diagnostic information, no single noninvasive parameter or test can reliably
      predict healing of existing wounds. Hyperglycemia has been identified as a risk
      factor for macrovascular disease but evidence to substantiate that improved
      glucose control affects vascular pathology or wound healing is limited.
      Similarly, the exact role of vascular endothelial growth factor or nicotine on
      vascular pathology and healing remains unclear. Although the literature may be
      mired in discrepancies, vascular health is known to affect healing. Further
      research to resolve controversy and to better direct care is needed.

PMID- 18057446
TI  - Honey and contemporary wound care: an overview.
AB  - A growing body of research and empirical evidence have supported the re-discovery
      of medicinal grade honey as a wound management agent. Pre-clinical study results
      suggest that honey has therapeutic benefit; clinical study results have shown
      that honey effectively addresses exudate, inflammation, devitalized tissue, and
      infection. Honey-containing dressings and gels have been developed to facilitate
      the application of medicinal-grade honey to the wound. Clinical studies to
      compare the safety and effectiveness of these products to other moisture
      retentive dressings and treatment modalities are warranted.

PMID- 18057447
TI  - Using an indentation measurement device to assess foam mattress quality.
AB  - Foam mattress quality affects pressure ulcer risk but no reliable method to
      assess mattress fatigue and indentation is available. To ascertain Indentation
      Quality values of standard 14-cm (5-inch) foam mattresses after 15 years of use,
      a convenience sample of 50 visco-elastic foam mattresses from a total of 1,000
      same-brand mattresses used in a Dutch University hospital was tested using a
      durometer. Indentation Quality values were obtained on the mattress cover at a
      relatively unloaded zone (corner), at the head and heel zones, the knee and
      shoulder areas, and in the middle (buttocks area). Indentation Quality values
      ranged from a mean of -11.91 mm (+/-2.58) in the unloaded zone to a mean of 
      26.96 mm (+/-4.31) in the middle zone (buttocks area, P <0.001 compared to all
      other mattress areas). The value at the relatively unloaded zone was
      significantly and positively related to the values at the head and the heel zones
      (r = .70, P <.01) and the knee and the shoulder zones (r = .33, P <.05). The
      value at the buttocks zone was positively related to the value at the knee and
      the shoulder zones (r = .35, P <.05). The study showed that mattresses that
      appeared similar had a wide range of indentation values (indicating a need for
      individual assessments to monitor their quality) and that Indentation Quality
      values, determined using the durometer, facilitate objective and quantifiable
      mattress assessments. Consideration of the consequences of foam mattress life
      span on quality of care, hospital management practices, and cost analysis is
      justified.

PMID- 18057448
TI  - Linoleic acid isomerase from Propionibacterium acnes: purification,
      characterization, molecular cloning, and heterologous expression.
AB  - Propionibacterium acnes strain ATCC 6919 catalyzes the isomerization of the
      double bond at the C9 position in linoleic acid (c9,c12, 18:2) to form t10,c12
      conjugated linoleic acid (CLA, 18:2). CLA has significant health benefits in
      animal and human. The linoleic acid C9 isomerase was purified to an apparent
      homogeneity by successive chromatography on diethylaminoethyl (DEAE) anion
      exchange, hydrophobic interaction, and chromatofocusing columns. Two degenerated
      oligonucleotide primers were synthesized according to the N-terminal peptide
      sequence to clone, by polymerase chain reaction (PCR), a short nucleotide
      sequence (62 bp) of the isomerase gene. The linoleic acid isomerase gene (lai)
      was subsequently cloned by inverse PCR. The amino acid sequence deduced from the
      lai coding sequence predicts a protein of 424 amino acid residues (48 kDa),
      excluding the N-terminal methionine, which was absent in the polypeptide purified
      from the native host. The isomerase shares no significant sequence homology to
      other enzymes except a flavin-binding domain in the N-terminal region. The
      recombinant isomerase purified from Escherichia coli showed a typical ultraviolet
      spectrum for FAD-bound proteins. The recombinant enzyme produced a single isomer
      of t10,c12-CLA from linoleic acid, as demonstrated by gas chromatography and gas
      chromatography-mass spectrum analysis. The recombinant isomerase protein was
      expressed at high levels in E. coli, but it was almost totally sequestered in
      inclusion bodies. The level of active isomerase was increased 376-fold by medium
      and process optimization in bench-scale fermentors.

PMID- 18057449
TI  - Developments in directed evolution for improving enzyme functions.
AB  - The engineering of enzymes with altered activity, specificity, and stability,
      using directed evolution techniques that mimic evolution on a laboratory
      timescale, is now well established. In vitro recombination techniques such as DNA
      shuffling, staggered extension process (StEP), random chimeragenesis on transient
      templates (RACHITT), iterative truncation for the creation of hybrid enzymes
      (ITCHY), recombined extension on truncated templates (RETT), and so on have been
      developed to mimic and accelerate nature's recombination strategy. This review
      discusses gradual advances in the techniques and strategies used for the directed
      evolution of biocatalytic enzymes aimed at improving the quality and potential of
      enzyme libraries, their advantages, and disadvantages.

PMID- 18057450
TI  - Optimization of fermentation parameters to enhance the production of ethanol from
      palmyra jaggery using Saccharomyces cerevisiae in a batch fermentor.
AB  - Application of statistical experimental designs for optimization of fermentation
      parameters to enhance ethanol production, which is an economical and renewable
      energy source using Saccharomyces cerevisiae NCIM 3090 from palmyra jaggery, was
      studied in a batch fermentor. Using Plackett-Burman design, impeller speed,
      concentrations of CoCl2 and KH2PO4 were identified as significant variables,
      which highly influenced ethanol production, and these variables were further
      optimized using a central composite design (CCD). The ethanol production was
      adequately approximated with a full quadratic equation obtained from three
      factors and five levels of CCD. Maximum ethanol concentration of 132.56 g/l
      (16.8% [v/v]) was obtained for an impeller speed of 247.179 ( approximately 250)
      rev/min, CoCl2 of 0.263 g/l and KH2PO4 of 2.39 g/l. A second-order polynomial
      regression model was fitted and was found adequate with R 2 of 0.8952. This
      combined statistical approach enables rapid identification and investigation of
      significant parameters for improving the ethanol production and could be very
      useful in optimizing processes.

PMID- 18057451
TI  - An organic soluble lipase for water-free synthesis of biodiesel.
AB  - Lipase AK was modified with short alkyl chains to form a highly organic soluble
      enzyme and was used to catalyze the synthesis of biodiesel from soybean oil in
      organic media. The effects of several key factors including water content,
      temperature, and solvent were examined for the solubilized enzyme in comparison
      with several other commercially available lipases. Whereas native lipases showed
      no activity in the absence of water, the organic soluble lipase demonstrated
      reaction rates of up to 33 g-product/g-enzyme h. The biocatalyst remains soluble
      in the biodiesel product, and therefore, there is no need to be removed because
      it is expected to be burned along with the diesel in combustion engines. This
      provides a promising one-pot mix-and-use strategy for biodiesel production.

PMID- 18057452
TI  - Comparison between different hydrolysis processes of vine-trimming waste to
      obtain hemicellulosic sugars for further lactic acid conversion.
AB  - Trimming vine shoot samples were treated with water under selected operational
      conditions (autohydrolysis reaction) to obtain a liquid phase containing
      hemicellulose-decomposition products. In a further acid-catalyzed step
      (posthydrolysis reaction), xylooligosaccharides were converted into single sugars
      for the biotechnological production of lactic acid using Lactobacillus pentosus.
      A wide range of temperatures, reaction times, and acid concentrations were tested
      during the autohydrolysis-posthydrolysis process to investigate their influence
      on hemicellulose solubilization and reaction products. The maximum concentration
      of hemicellulosic sugars was achieved using autohydrolysis at 210 degrees C
      followed by posthydrolysis with 1% H2SO4 during 2 h. Data from autohydrolysis
      posthydrolysis were compared with the results obtained at the optima conditions
      assayed for prehydrolysis (3% H2SO4 at 130 degrees C during 15 min) based on
      previous works. Prehydrolysis extracted more hemicellulosic sugars from trimming
      vine shoots; however, the protein content in the hydrolysates from autohydrolysis
      posthydrolysis was higher. The harsher conditions assayed during the
      autohydrolysis process and the higher content of protein after this treatment
      could induce Maillard reactions decreasing consequently the concentration of
      hemicellulosic sugars in the hydrolysates. Therefore, despite the several
      advantages of autohydrolysis (less equipment caused by the absence of mineral
      acid, less generation of neutralized sludges, and low cost of reagents) the poor
      results obtained in this work with no detoxified hydrolysates (Q P = 0.36 g/L h,
      Q S = 0.79 g/L h, Y P/S = 0.45 g/g, Y P/Sth = 61.5 %) or charcoal-treated
      hydrolysates (Q P = 0.76 g/L h, Q S = 1.47 g/L h, Y P/S = 0.52 g/g, Y P/Sth =
      71.5 %) suggest that prehydrolysis of trimming vine shoots with diluted H2SO4 is
      more attractive than autohydrolysis-posthydrolysis for obtaining lactic acid
      through fermentation of hemicellulosic sugars with L. pentosus. Besides the
      higher hemicellulosic sugars concentration achieved when using the prehydrolysis
      technology, no detoxification steps are required to produce efficiently lactic
      acid (Q P = 1.14 g/L h; Q S = 1.64 g/L h; Y P/S = 0.70 g/g; Y P/Sth = 92.6 %),
      even when vinification lees are used as nutrients (Q P = 0.89 g/L h; Q S = 1.54
      g/L h; Y P/S = 0.58 g/g; Y P/Sth = 76.1 %).

PMID- 18057453
TI  - Whey treatment by AnSBBR with circulation: effects of organic loading, shock
      loads, and alkalinity supplementation.
AB  - The main objective of this work was to investigate the effect of volumetric
      loading rate (VLR), shock load, and alkalinity supplementation on the efficiency
      and stability of an Anaerobic Sequencing Batch Biofilm Reactor (AnSBBR)
      containing polyurethane foam cubes. Mixing in the reactor, which was kept at 30
      +/- 1 degrees C, occurred by recirculating the liquid phase. The reactor treated
      2.5 l cheese whey in 8-h cycles, at concentrations of 1, 2, and 4 g COD l-1,
      which corresponded to VLRs of 3, 6, and 12 g COD l-1 day-1, respectively.
      Application of single-cycle shock loads of 6, 12, and 24 g COD l-1 day-1 did not
      impair reactor performance. In addition, for VLRs of 3, 6, and 12 g COD l-1 day
      1, alkalinity supplementation to the influent, at the end of each assay, could be
      reduced to 75, 50, and 50%, respectively, in relation to supplementation at the
      beginning of the assay. During reactor operation a viscous polymer-like material
      was formed between the polyurethane foam cubes, which increased at higher VLR.
      Finally, addition of salts to the influent improved reactor efficiency.

PMID- 18057454
TI  - Improvement and modelling of hexenal transfer in liquid-gas reactor.
AB  - The aim of the present work is to improve the extraction of an aromatic compound,
      2E-hexenal, from a continuous liquid-gas reactor. Having an improved process to
      recover hexenal could be of interest to obtain this chemical if produced by any
      biotechnological process. The experimental program proposed on the basis of a
      full 23 factorial design demonstrated that the conditions optima for the
      extraction are 40 degrees C as a reactor temperature and -10 degrees C as a
      temperature of trap for a nitrogen flow of 45 mL s-1. These conditions allowed to
      recover more than 75% of hexenal, when this compound was stripping by a nitrogen
      stream from the liquid phase. The mass transfer was theoretically and
      experimentally studied. The model predictions were validated against experimental
      results obtained for a reactor, and good correlation was observed for a
      simulation.

PMID- 18057455
TI  - Comparison of different pretreatment strategies for enzymatic hydrolysis of wheat
      and barley straw.
AB  - In biomass-to-ethanol processes a physico-chemical pretreatment of the
      lignocellulosic biomass is a critical requirement for enhancing the accessibility
      of the cellulose substrate to enzymatic attack. This report evaluates the
      efficacy on barley and wheat straw of three different pretreatment procedures:
      acid or water impregnation followed by steam explosion versus hot water
      extraction. The pretreatments were compared after enzyme treatment using a
      cellulase enzyme system, Celluclast 1.5 L from Trichoderma reesei, and a beta
      glucosidase, Novozyme 188 from Aspergillus niger. Barley straw generally produced
      higher glucose concentrations after enzymatic hydrolysis than wheat straw. Acid
      or water impregnation followed by steam explosion of barley straw was the best
      pretreatment in terms of resulting glucose concentration in the liquid
      hydrolysate after enzymatic hydrolysis. When the glucose concentrations obtained
      after enzymatic hydrolyses were related to the potential glucose present in the
      pretreated residues, the highest yield, approximately 48% (g g-1), was obtained
      with hot water extraction pretreatment of barley straw; this pretreatment also
      produced highest yields for wheat straw, producing a glucose yield of
      approximately 39% (g g-1). Addition of extra enzyme (Celluclast 1.5 L+Novozyme
      188) during enzymatic hydrolysis resulted in the highest total glucose
      concentrations from barley straw, 32-39 g L-1, but the relative increases in
      glucose yields were higher on wheat straw than on barley straw. Maldi-TOF MS
      analyses of supernatants of pretreated barley and wheat straw samples subjected
      to acid and water impregnation, respectively, and steam explosion, revealed that
      the water impregnated + steam-exploded samples gave a wider range of pentose
      oligomers than the corresponding acid-impregnated samples.

PMID- 18057456
TI  - Ageing and polymorbidity: is there a mismatch between the training of internists
      and the need?

PMID- 18057457
TI  - The diagnosis of disseminated intravascular coagulation made easy.

PMID- 18057458
TI  - Mediastinal emphysema complicating diabetic ketoacidosis: plea for conservative
      diagnostic approach.
AB  - BACKGROUND: Spontaneous pneumomediastinum has been infrequently reported as a
      complication of diabetic ketoacidosis. Evidence-based guidelines are currently
      not available to help in choosing the best diagnostic approach. METHODS: We
      conducted a systematic review of the literature and looked for diagnostic clues
      that might indicate the need for a work-up to rule out oesophageal perforation.
      RESULTS: In all 56 published cases of spontaneous pneumomediastinum associated
      with diabetic ketoacidosis, the condition was self-limiting. We report one
      additional case of a 31-year-old female who presented with a spontaneous
      pneumomediastinum and also epidural pneumatosis, complicating diabetic
      ketoacidosis. CONCLUSION: Important pathology, such as oesophageal rupture, was
      not detected in any of the reported cases, and we suggest a restrictive
      diagnostic work-up.

PMID- 18057459
TI  - Liver transplantation: an update.
AB  - Liver transplantation has been an accepted treatment for end-stage liver disease
      since the 1980s. Currently it is a highly successful treatment for this
      indication. The aim of this review is to give a general update on recent
      developments in the field of liver transplantation. In the last decades
      considerable progress has been made in the care of liver transplant candidates
      and recipients. At present the one- and five-year patient survival rates are
      approximately 85 and 75%. The indications for liver transplantation are shifting
      and the number of absolute contraindications is decreasing. In the coming years,
      an increase in the number of transplant candidates can be expected. An important
      problem is the shortage of donor organs, for which many solutions are being
      explored. A recently introduced method for recipient selection is the MELD score
      using simple laboratory measurements. Perioperative care at the present time is
      characterised by a high degree of standardisation and rapidly declining blood
      loss during transplantation. Long-term care includes awareness and management of
      recurrent disease. Important causes of morbidity and mortality such as de novo
      malignancies and cardiovascular disease should be adequately screened for and
      managed. With the increasing success of liver transplantation, physicians should
      aim at reaching a normal life expectancy and quality of life for transplant
      recipients.

PMID- 18057460
TI  - Reversible hypogammaglobulinaemia.
AB  - In this report we present four patients with reversible hypogammaglobulinaemia
      who required immunoglobulin substitution for several years. One patient had
      documented systemic lupus erythematosus (SLE), the other three patients had
      primary hypogammaglobulinaemia without known cause. Whereas the cessation of
      azathioprine therapy may have contributed to the recovery in the patient with
      SLE, the restoration of the immunoglobulin production in the other three patients
      occurred spontaneously. All four patients were IgA deficient when the
      hypogammaglobulinaemia was first detected and remained so after IgM and IgG
      production had recovered. Two of the three patients who also had anti-IgA
      antibodies started to produce anti-IgA again after stopping the immunoglobulin
      substitution. We conclude that recovery of hypogammaglobulinaemia is possible but
      rare. When recovery is suspected, we recommend that immunoglobulin substitution
      is stopped and the antibody response to vaccination is tested.

PMID- 18057461
TI  - Intracranial multiple midline germinomas: is histological verification crucial
      for therapy?
AB  - In this report we present two patients with intracranial multiple midline tumours
      in the suprasellar region and pineal gland. We postulate that in a patient with
      multiple midline tumours and normal values of the tumour markers human chorionic
      gonadotropin and alpha-fetoprotein in serum and cerebrospinal fluid, the only
      possible diagnosis is a germinoma. In such a situation no histological
      confirmation is required to start low-dose radiotherapy.

PMID- 18057462
TI  - Interstitial lung disease as the first manifestation of systemic sclerosis.
AB  - We describe three patients with progressive fibrosing interstitial lung disease
      (ILD) as the first and only manifestation of systemic sclerosis. In one patient
      the presence of anti-Scl-70 autoantibodies suggested systemic sclerosis to be the
      underlying cause of the disease. In the two other subjects, however, anti-Scl-70
      antibodies were negative. In these patients the lung disease preceded other
      manifestations of systemic sclerosis by several years. Diagnosis, prognosis and
      treatment of systemic sclerosisassociated ILD is discussed.

PMID- 18057463
TI  - A patient with hyperglycaemia and normal HbA Ic due to impaired glycation.
AB  - A diabetic Caucasian woman presented with discrepantly low HbA Ic values compared
      with her glycaemia. High-performance liquid chromatography (HPLC) analysis
      disclosed 80% HbA and 20% HbI Philadelphia (I6alpha2 lys --> glut). The
      calculated glycosylation gap from the fructosamine level was 1.2%. The
      haemoglobin alpha/beta glycation ratios, as measured by electron spray ionisation
      mass spectroscopy (ESI-MS), for the patient and her three children also carrying
      the mutation were decreased by values of 0.56 and 0.51, 0.50 and 0.49,
      respectively (reference value 0.66).

PMID- 18057464
TI  - Disseminated intravascular coagulation and a negative D-dimer test.
AB  - The diagnosis of disseminated intravascular coagulation (DIC) requires the
      presence of a fibrin-related marker. D-dimer is frequently used in clinical
      practice as a fibrin-related marker. We present a case of paraneoplastic DIC with
      a false-negative D-dimer test. Repeating the test using a different D-dimer assay
      as well as the measurement of other fibrinolysis markers confirmed the diagnosis
      of DIC.

PMID- 18057465
TI  - Chronic pancreatitis resulting from genetic mutations in trypsin and trypsin
      inhibitors.

PMID- 18057466
TI  - Hydatid liver cyst ruptured into vena cava inferior.

PMID- 18057468
TI  - A patient with a large periumbilical bruise and acute abdominal pain.

PMID- 18057469
TI  - An unusual cause of rectal bleeding.

PMID- 18057470
TI  - [HPV vaccination and cervical cancer screening].

PMID- 18057471
TI  - [The use of methylphenidate in children with ADHD].

PMID- 18057473
TI  - [Special observation on psychiatric patients on acute inpatient wards at the
      Division of Psychiatry, Landspitali-University Hospital in Iceland, attitudes of
      patients and staff].
AB  - OBJECTIVE: Special observation (constant observation) of patients is common on
      psychiatric wards, both in Iceland and abroad, but very few studies have been
      conducted on their therapeutic value. The objective was to investigate the extent
      and nature of special observation on emergency wards at the division of
      psychiatry at the Landspitali-University Hospital in Iceland as well as the
      attitudes of patients and staff toward special observation. PARTICIPANTS AND
      METHODS: Information about patients on special observation was recorded over a
      three months period. Patients were interviewed with a standardised eleven
      questions interview shortly after the observation finished in order to
      investigate their attitudes toward the observation. Also, members of staff from
      each ward were asked to answer eight questions about their attitudes toward
      special observation in general. The Ethics Committee of Landspitali - University
      Hospital gave its permission for the study. RESULTS: During the research period
      observation was used for 157 patients, which is 31% of the total number of
      patients admitted during that period. Most of the patients (83%) were on 5-15
      minutes observation, 25 per cent on close observation and 11 percent on suicide
      or constant observation. The majority of the patients claimed that security was
      the most important aspect of being on special observation, independent of which
      type of observation they were, and only one fifth felt that the company of staff
      was most important. The staff members on the other hand claimed that concern for
      the patient, respect and companionship were most important for the patients,
      independent of the type of observation used. CONCLUSIONS: The extent, nature and
      process of observation on acute inpatient wards in Iceland seems to be comparable
      to other studies from abroad. In view of the importance of special observations
      in psychiatric emergency care and their influence on patients' private life it is
      important to develop and implement clinical guidelines about their use.

PMID- 18057472
TI  - [Use of methylphenidate among children in Iceland 1989-2006].
AB  - STUDY OBJECTIVE: To determine the prevalence of methylphenidate use among
      children in Iceland and show utilization trends from 1989 to 2006. Patterns of
      use were analyzed by sex, age and region of habitation, short-acting vs. long
      acting formulations and presciber's specialty. MATERIALS AND METHODS: A
      descriptive observational study. Data was retrieved from the nationwide Register
      on Prescribed Drugs in Iceland and the Icelandic Directorate of Health
      surveillance system on prescribed methylphenidate. The study population
      encompassed the total pediatric population (0-18 year-olds) in Iceland during the
      study period. Total, sex-, age, and region-specific yearly prevalence rates were
      computed. Specific prevalence rates of short-acting and long-acting
      methylphenidate use were compared. Prescribed volume and number of prescriptions
      were analyzed in relation to specialty of prescriber. Prevalence ( per thousand)
      was defined as the number of children per 1,000 children in the population who
      received at least one methylphenidate prescription in the given year. RESULTS:
      The total prevalence of methylphenidate use among children (0-18) in Iceland was
      0.2 per thousand in 1989 and 25.1 per thousand in 2006. Overall use was three
      times more common among boys than girls. Prevalence was highest at age 10, 77.4
      per thousand among boys and 24.3 per thousand among girls. A variance in use
      between regions was detected. Prevalence of short-acting methylphenidate use
      decreased from 2003 (18.7 per thousand) to 2006 (6.8 per thousand), while
      prevalence of long-acting medication increased from 14.4 per thousand to 24.6 per
      thousand. In 2006 pediatricians were the most common prescribers of
      methylphenidate to children in Iceland, accounting for 41% of prescriptions.
      CONCLUSION: Use of methylphenidate among children in Iceland increased
      considerably from 1989 to 2004, when a plateau seems to have been reached. In
      accordance with the trend in many Western countries, a rise in use of long-acting
      drugs was detected concurrently with a steep decrease in use of short-acting
      drugs. Compared to utilization rates in Europe, prevalence of methylphenidate use
      among children in Iceland is high.

PMID- 18057474
TI  - [Prevalence, diagnosis and treatment of depression and anxiety in patients in
      cardiac rehabilitation].
AB  - OBJECTIVE: The aim of this study was to estimate the prevalence of depression and
      anxiety among patients in cardiac rehabilitation at Reykjalundur Rehabilitation
      Center and to study the impact of a 4-5 weeks inpatient cardiac rehabilitation
      program on these symptoms. Secondly we wished to compare the concordance of our
      clinical diagnosis with the results of a standardized psychometric scale,
      Hospital Anxiety and Depression scale, HAD. MATERIALS AND METHODS: Of 224
      patients in one year, 200 (89.3%) were included in the study, 151 men and 49
      women. The patients were first evaluated by a doctor and a nurse separately at
      the arrival and a clinical evaluation was made jointly. Shortly after arrival and
      before departure a HAD questionnaire was to be answered. All new psychiatric
      treatment was recorded. RESULTS: Prevalence of depression as measured by HAD was
      reduced from 9.5% to 3.1% and anxiety from 11.6% to 2.5%. The sensitivity of
      clinical diagnosis of depression as compared to the results of HAD was 73.7% and
      specificity 87.3%. For anxiety the sensitivity was 86.4% and specificity was
      79.2%. The predictive value of a positive clinical diagnosis of depressions was
      37.8% and anxiety 33.9%, but predictive value of a negative clinical diagnosis
      was 96.9% and anxiety 97.9% respectively. CONCLUSION: The prevalence of
      depression and anxiety is similar or somewhat lower than in other studies on
      patients with cardiac diseases. The agreement of clinical diagnosis and HAD
      questionnaire was acceptable and the questionnaire will not be used routinely. A
      comprehensive cardiac rehabilitation program seems to reduce substancially
      symptoms of depression and anxiety among patients in cardiac rehabilitation at
      Reykjalundur.

PMID- 18057475
TI  - Research in pediatric practice: an untapped arena.

PMID- 18057476
TI  - Simple clinical sings to identify severe neonatal illness.

PMID- 18057477
TI  - Vitamin K1 versus vitamin K3 for prevention of subclinical vitamin deficiency: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare efficacy of intramuscular phytomenadione (fat soluble
      vitamin K or vitamin K1) with menadione (water soluble vitamin K or vitamin K3)
      in prevention of subclinical vitamin K deficiency. DESIGN: A doubleblind
      randomized controlled trial. SETTINGS: Tertiary care hospital. METHODS: Healthy
      term neonates were randomized to receive 1 mg of either phytomenadione (Group I,
      n = 85) or menadione (Group II, n = 85) intramuscularly within 2 hours of birth.
      PIVKA-II, a sensitive and specific marker of vitamin K deficiency was measured by
      ELISA method (Diagnostica Stago, France). Plasma level > 2 ng/mL was labeled as
      detectable PIVKA-II. RESULTS: Birth weight (2914 +/- 318 vs 2958 +/- 312 g),
      gestation (38.4 +/- 1.2 vs 38.4 +/- 1.0 wk) and other baseline variables were
      comparable between the two groups. 48.2% (41/85) neonates in Group I and
      44.7%(38/85) neonates in Group II had detectable PIVKAII levels ([Relative Risk
      (95% confidence interval): 1.1 (0.8-1.5); P = 0.76]). Median PIVKA-II levels in
      Group I and Group II were 1.99 ng/mL and 1.97 ng/mL respectively (P = 0.26). At
      72 +/- 12 h of age, mean packed cell volume and mean serum bilirubin levels were
      comparable in the two groups. CONCLUSION: Comparable PIVKAII detection rate and
      PIVKAII levels in neonates receiving phytomenadione or menadione indicate their
      similar efficacy in prevention of vitamin K deficiency. However, high PIVKAII
      detection rate observed with both preparations indicates recent vitamin K
      deficiency and may be due to either inadequate dose of vitamin K or persistence
      of PIVKAII of fetal origin.

PMID- 18057478
TI  - Effect of consumption of micronutrient fortified candies on the iron and vitamin
      A status of children aged 3-6 years in rural Haryana.
AB  - OBJECTIVE: To assess the efficacy of micronutrient fortified sugar candies in
      improving the iron and vitamin A status in children aged 3 to 6 years. DESIGN:
      Triple blind randomized controlled trial. SETTINGS: Anganwadis and preparatory
      schools in rural Haryana. METHODS: 410 children were randomized in four groups.
      One group received full dose candy (vitamin A 1000 IU and 14 mg elemental iron)
      daily, the second group received full dose candy for 3 days a week, the third
      group received half dose candy (vitamin A 500 IU and 7 mg elemental iron) daily
      and the fourth received placebo. The candies were provided to children under
      supervision of field workers. Hemoglobin, S. ferritin, S. retinol and S. retinol
      binding protein levels were estimated at baseline and after 13 weeks of
      intervention. RESULTS: The increase in hemoglobin was least in the placebo group
      (0.3 g/dL) as compared to the two full dose groups (1.15-1.18 g/dL, P < 0.001).
      Among anemic children, the increase in hemoglobin was about 2 g/dL in the full
      dose group and 0.7 g/dL in the placebo group (P < 0.001). S. ferritin levels
      increased significantly only in the full dose daily group (p < 0.05). The
      prevalence of anemia decreased from around 50% at baseline to 9.6% in the full
      dose daily group (p < 0.01). Based on the S. retinol levels, the study area was
      not vitamin A deficient and the intervention did not result in a significant
      improvement in the vitamin A status of the children. CONCLUSION: Micronutrient
      fortified candies were effective in improving the hemoglobin level and decreasing
      anemia prevalence. It could serve as a suitable vehicle for micronutrient
      supplementation in children and other target groups.

PMID- 18057479
TI  - Fluconazole prophylaxis against fungal colonization and invasive fungal infection
      in very low birth weight infants.
AB  - BACKGROUND: Fungal infections are common cause of morbidity and mortality in very
      low birth weight Infants OBJECTIVES: To evaluate the efficacy of prophylactic
      Fluconazole in preventing fungal colonization and invasive fungal infection in
      VLBW infants. DESIGN: Prospective, randomized, double blind placebo controlled
      clinical trial. SETTING: Tertiary level Neonatal intensive care unit. SUBJECTS:
      120 preterm infants with birth Weight < 1500 g. INTERVENTION: Infants were
      randomly assigned during first three days to receive either Fluconazole or
      placebo till 28 days or less if, discharged or died earlier. Weekly surveillance
      cultures from groin, oropharynx, rectum and blood were collected in all patients.
      Fungal isolates were typed based on standard microbiologic techniques. Liver
      enzymes were monitored. RESULTS: Baseline risk factors for fungal infection in
      Fluconazole and Placebo groups were similar. Fungal colonization was seen in 30
      infants (50%) in the placebo group and 11 infants (19%) in the Fluconazole group
      (P <0.001). Fungal colonization at rectum, groin and oropharynx was less in
      fluconazole groups. Fluconazole group showed significantly lower colonizations
      with Candida albicans but not with C. glabrata. Invasive infection was seen in 15
      (25%) infants in Placebo group and 16 (26.7%) infants in Fluconazole group (P =
      0.835). Various non-albicans Candida were responsible for 96.8% cases of invasive
      fungal infection (Candida glabrata 71%, C. parapsilosis 14.7% and C. tropicalis
      9.6%). No significant hepatotoxicity was noticed during Fluconazole therapy.
      CONCLUSION: Prophylactic fluconazole during the first four weeks of life is
      effective in reducing fungal colonization but not invasive infection in VLBW
      infants.

PMID- 18057480
TI  - Cefpodoxime proxetil compared with cefixime for treatment of typhoid fever in
      children.
AB  - In order to evaluate clinical and bacteriological efficacy of Cefpodoxime
      Proxetil (CP) in typhoid fever in comparison to cefixime (CF), we assessed 140
      children with suspected typhoid fever. Fulfilling inclusion criteria finally 40
      culture confirmed typhoid fever were allocated in randomized double blind
      clinical trial (RCT) to receive therapy with either oral CP (16 mg/kg/day, n =
      21) or oral CF (20 mg/kg/day, n = 19) for 10 days. The two groups were comparable
      in their clinical and baseline characteristics. The clinical efficacy was similar
      in the two groups with only 2 (one in each group) clinical failures and all
      showing bacteriological eradication on subsequent blood culture. The time of
      defervescence was comparable in both groups (4.87 Fluconazole Prophylaxis against
      Fungal Colonization and Invasive Fungal Infection in Very Low Birth Weight
      Infants 2.33 vs 4.27 +/- 2.28 days, P = 0.308), with no relapse during 3 months
      follow up and no significant adverse effect. CP reduced the treatment cost by 33%
      in comparison to cefixime. Our study suggests CP is effective, safe and cheaper
      oral option for treatment of typhoid fever in children.

PMID- 18057481
TI  - Intramuscular injection practices among infants.
AB  - Administration of unnecessary Intramuscular (i.m.) Injections to infants for
      trivial illness is a common problem. This descriptive study included 120 infants
      who received at least one i.m. injection for their current illness. Data were
      collected using semi structured questionnaire to their mothers. 91% of infants
      received unnecessary i.m. injections for minor problems like upper respiratory
      tract infection. I.m. injections were administered at the wrong site in 97% of
      the infants. Information regarding i.m. injections was inadequate in mothers.
      Intensive health education regarding safe injection practices for the public and
      health care providers is essential.

PMID- 18057482
TI  - Make routine immunization compulsory.

PMID- 18057483
TI  - Snake bite: an unusual cause of acute abdominal pain.
AB  - Pain abdomen is one of the most commonly encountered complaints in pediatric
      emergency room. We report a seven-year-old resident of Delhi, who presented with
      sudden onset abdominal pain for three hours, and later went on to develop neuro
      muscular paralysis and respiratory failure. The cause was found to be snake-bite.
      The child had a stormy course and full recovery.

PMID- 18057484
TI  - Oral-facial digital syndrome type 1.
AB  - The oral-facial-digital syndrome type 1 is characterized by following
      abnormalities: pseudocleft of the upper lip, tongue lobulation, hamartomata on
      the tongue, alveolar frenulae, and clefting of the soft palate. We report a 9
      month-old girl who was referred to our clinic due to facial dysmorphology in
      addition to cleft palate and multiple masses on the tongue which resulted in
      feeding problems. Surgical intervention was done. Molecular analysis revealed
      absence of OFD gene.

PMID- 18057485
TI  - Intracranial calcification in beta-thalassemia major.
AB  - A 13-year-old boy with thalassemia major presented with generalized seizures. He
      was non-chelated and had hypoparathyroidism with extensive intracranial
      calcification, an association that is rarely reported.

PMID- 18057486
TI  - Suprasellar arachnoid cyst with delayed puberty.
AB  - A 15-year-old female presented with primary amenorrhea and delayed onset of
      secondary sexual characteristics. Earlier she was operated for endoscopic third
      ventriculostomy (ETV) for a tense suprasellar arachnoid cyst with obstructive
      hydrocephalus. MRI revealed recurrence of hydrocephalus. Hormonal levels were
      suggestive of hypogonadism and deficiency of growth hormone. She was operated for
      fenestration of cyst. In this case, suprasellar arachnoid cyst presented with
      delayed puberty, which is unusual.

PMID- 18057487
TI  - Bullous systemic lupus erythematosus and lupus nephritis in a 10 year old boy.
AB  - Systemic lupus erythematosus (SLE) is an episodic, potentially fatal, multisystem
      autoimmune disease characterized by the presence of antinuclear antibodies
      especially to double stranded DNA. Bullous systemic lupus erythematosus is an
      extremely rare subset of lupus erythematosus. We report a 10-year-old boy with
      bullous SLE and nephrotic syndrome.

PMID- 18057488
TI  - Chemotherapy induced transverse leukonychia (Mees lines).

PMID- 18057489
TI  - National PPTCT (Prevention of Parent to Child Transmission) of HIV drug protocol-
      urgent need for a change.

PMID- 18057491
TI  - Tuberculosis infection in BCG vaccinated children.

PMID- 18057492
TI  - Usefulness of dTPa.

PMID- 18057494
TI  - Boostrix.

PMID- 18057495
TI  - Management of severely malnourished children.

PMID- 18057498
TI  - Probiotics and diarrhea.

PMID- 18057499
TI  - Hospital management of severely malnourished children.

PMID- 18057501
TI  - Self-initiation of EEG-based brain-computer communication using the heart rate
      response.
AB  - Self-initiation, that is the ability of a brain-computer interface (BCI) user to
      autonomously switch on and off the system, is a very important issue. In this
      work we analyze whether the respiratory heart rate response, induced by brisk
      inspiration, can be used as an additional communication channel. After only 20
      min of feedback training, ten healthy subjects were able to self-initiate and
      operate a 4-class steady-state visual evoked potential-based (SSVEP) BCI by using
      one bipolar ECG and one bipolar EEG channel only. Threshold detection was used to
      measure a beat-to-beat heart rate increase. Despite this simple method, during a
      30 min evaluation period on average only 2.9 non-intentional switches (heart rate
      changes) were detected.

PMID- 18057502
TI  - Synchronous neural interactions assessed by magnetoencephalography: a functional
      biomarker for brain disorders.
AB  - We report on a test to assess the dynamic brain function at high temporal
      resolution using magnetoencephalography (MEG). The essence of the test is the
      measurement of the dynamic synchronous neural interactions, an essential aspect
      of the brain function. MEG signals were recorded from 248 axial gradiometers
      while 142 human subjects fixated a spot of light for 45-60 s. After fitting an
      autoregressive integrative moving average (ARIMA) model and taking the stationary
      residuals, all pairwise, zero-lag, partial cross-correlations (PCC(ij)(0)) and
      their z-transforms (z(ij)(0)) between i and j sensors were calculated, providing
      estimates of the strength and sign (positive, negative) of direct synchronous
      coupling at 1 ms temporal resolution. We found that subsets of z(ij)(0)
      successfully classified individual subjects to their respective groups (multiple
      sclerosis, Alzheimer's disease, schizophrenia, Sjogren's syndrome, chronic
      alcoholism, facial pain, healthy controls) and gave excellent external cross
      validation results.

PMID- 18057503
TI  - Intraspinal stimulation for bladder voiding in cats before and after chronic
      spinal cord injury.
AB  - The long-term objective of this study is to develop neural prostheses for people
      with spinal cord injuries who are unable to voluntarily control their bladder.
      This feasibility study was performed in 22 adult cats. We implanted an array of
      microelectrodes into locations in the sacral spinal cord that are involved in the
      control of micturition reflexes. The effect of microelectrode stimulation was
      studied under light Propofol anesthesia at monthly intervals for up to 14 months.
      We found that electrical stimulation in the sacral parasympathetic nucleus at
      S(2) level or in adjacent ventrolateral white matter produced bladder
      contractions insufficient for inducing voiding, while stimulation at or
      immediately dorsal to the dorsal gray commissure at S(1) level produced strong
      (at least 20 mmHg) bladder contractions as well as strong (at least 40 mm Hg)
      external urethral sphincter relaxation, resulting in bladder voiding in 14
      animals. In a subset of three animals, spinal cord transection was performed. For
      several months after the transection, intraspinal stimulation continued to be
      similarly or even more effective in inducing the bladder voiding as before the
      transection. We speculate that in the absence of the supraspinal connections, the
      plasticity in the local spinal circuitry played a role in the improved
      responsiveness to intraspinal stimulation.

PMID- 18057505
TI  - Output-based comparison of alternative kinetic schemes for the NMDA receptor
      within a glutamate spillover model.
AB  - Recent experimental and theoretical work continues to explore the mechanisms and
      implications of neurotransmitter spillover. Here we examine N-methyl-D-aspartate
      receptor (NMDA-R) kinetics to determine their implication(s) in glutamate
      spillover by comparing two mechanistically different NMDA-R models, the 5-state
      Lester and Jahr (LJ) model and the 8-state Banke and Traynelis (BT) model, within
      the context of a glutamate spillover model. We employ a search-survey-and
      summarize strategy to analyze the relationships within model behavior (model
      relational analysis) and form a model output landscape. Our results indicate that
      model relational analysis can reveal differences in models whose outputs would be
      considered the same. The analysis reveals that the BT model, with its more
      complex kinetics, is less reliant on diffusion compared to the LJ version,
      resulting in differences in the relationships between open probability and
      glutamate concentration despite the fact that both model versions were able to
      produce the same target output values. Additionally, model relational analysis is
      able to distinguish between the BT and LJ NMDA-R model versions even though
      factor analysis indicates that the overall model output space dimensions are the
      same for both NMDA-R models. Furthermore, the work presented here suggests that
      model relational analysis may be broadly applicable as a means to examine the
      complex interactions hidden within overall model behavior.

PMID- 18057504
TI  - Prediction of upper limb muscle activity from motor cortical discharge during
      reaching.
AB  - Movement representation by the motor cortex (M1) has been a theoretical interest
      for many years, but in the past several years it has become a more practical
      question, with the advent of the brain-machine interface. An increasing number of
      groups have demonstrated the ability to predict a variety of kinematic signals on
      the basis of M1 recordings and to use these predictions to control the movement
      of a cursor or robotic limb. We, on the other hand, have undertaken the
      prediction of myoelectric (EMG) signals recorded from various muscles of the arm
      and hand during button pressing and prehension movements. We have shown that
      these signals can be predicted with accuracy that is similar to that of kinematic
      signals, despite their stochastic nature and greater bandwidth. The predictions
      were made using a subset of 12 or 16 neural signals selected in the order of each
      signal's unique, output-related information content. The accuracy of the
      resultant predictions remained stable through a typical experimental session.
      Accuracy remained above 80% of its initial level for most muscles even across
      periods as long as two weeks. We are exploring the use of these predictions as
      control signals for neuromuscular electrical stimulation in quadriplegic
      patients.

PMID- 18057506
TI  - Effects of ramped amplitude waveforms on the onset response of high-frequency
      mammalian nerve block.
AB  - Though high-frequency alternating current (HFAC) can block nerve conduction, the
      block is invariably preceded by an onset response which is a period of repetitive
      nerve firing. We tested the hypothesis that slowly ramping up the amplitude of
      the HFAC waveform could produce block without this initial onset response.
      Computer simulations were performed, using the McIntyre-Richardson-Grill (MRG)
      model of myelinated mammalian axon. A ramped-amplitude HFAC was applied to axons
      of diameters ranging from 7.3 microm to 16 microm and at frequencies ranging from
      3125 Hz to 40 kHz. The ramped-amplitude HFAC was also investigated in vivo in
      preparations of rat sciatic nerve. Sinusoidal voltage-regulated waveforms, at
      frequencies between 10 kHz and 30 kHz, were applied with initial amplitudes of 0
      V, linearly increasing with time to 10 V. Ramp durations ranged from 0 s to 60 s.
      In both the MRG model simulations and the experiments, ramping the HFAC waveform
      did not eliminate the onset response. In the rat experiments, the peak amplitude
      of the onset response was lessened by ramping the amplitude, but both the onset
      response duration and the amount of onset activity as measured by the force-time
      integral were increased.

PMID- 18057507
TI  - Three-dimensional hydrogel cultures for modeling changes in tissue impedance
      around microfabricated neural probes.
AB  - One limitation to the use of neuroprosthestic devices for chronic application, in
      the treatment of disease, is the reactive cell responses that occur surrounding
      the device after insertion. These cell and tissue responses result in increases
      in device impedance and failure of the device to interact with target populations
      of neurons. However, few tools are available to assess which components of the
      reactive response contribute most to changes in tissue impedance. An in vitro
      culture system has been developed that is capable of assessing individual
      components of the reactive response. The system utilizes alginate cell
      encapsulation to construct three-dimensional architectures that approach the cell
      densities found in rat cortex. The system was constructed around neuroNexus acute
      probes with on-board circuitry capable of monitoring the electrical properties of
      the surrounding tissue. This study demonstrates the utility of the system by
      demonstrating that differences in cell density within the three-dimensional
      alginate constructs result in differences in resistance and capacitance as
      measured by electrochemical impedance spectroscopy. We propose that this system
      can be used to model components of the reactive responses in brain tissue, and
      that the measurements recorded in vitro are comparable to measurements recorded
      in vivo.

PMID- 18057508
TI  - Complex impedance spectroscopy for monitoring tissue responses to inserted neural
      implants.
AB  - A series of animal experiments was conducted to characterize changes in the
      complex impedance of chronically implanted electrodes in neural tissue.
      Consistent trends in impedance changes were observed across all animals,
      characterized as a general increase in the measured impedance magnitude at 1 kHz.
      Impedance changes reach a peak approximately 7 days post-implant. Reactive
      responses around individual electrodes were described using immuno- and histo
      chemistry and confocal microscopy. These observations were compared to measured
      impedance changes. Several features of impedance changes were able to
      differentiate between confined and extensive histological reactions. In general,
      impedance magnitude at 1 kHz was significantly increased in extensive reactions,
      starting about 4 days post-implant. Electrodes with extensive reactions also
      displayed impedance spectra with a characteristic change at high frequencies.
      This change was manifested in the formation of a semi-circular arc in the Nyquist
      space, suggestive of increased cellular density in close proximity to the
      electrode site. These results suggest that changes in impedance spectra are
      directly influenced by cellular distributions around implanted electrodes over
      time and that impedance measurements may provide an online assessment of cellular
      reactions to implanted devices.

PMID- 18057509
TI  - Comment on 'Analysis of electroencephalograms in Alzheimer's disease patients
      with multiscale entropy'.
AB  - In the article by Escudero et al (2006), there are only random samples, which are
      useful for the validity of the study design. In this author's opinion, there are
      still other clinicophysiological characteristics that merit consideration and
      scrutiny as discussed below. The hypothesis set by the original authors needs to
      be adequately justified. Their hypothesis appears to be that the multiscale
      entropy (MSE) is positively related to a non-linear analysis of an
      electroencephalogram on patients with Alzheimer's disease.

PMID- 18057511
TI  - Quantification of lung injury using ventilation and perfusion distributions
      obtained from gamma scintigraphy.
AB  - This paper explores the potential of isotope V/Q lung scans to quantify lung
      disease. Areas of restricted perfusion in subjects with a pulmonary embolus (PE)
      were identified in 3D reconstructions of V/Q images achieved using anatomical
      data from the Visible Human Project. From these, the extent of lung damage was
      quantified. Significant differences in the values of both LogSD V and LogSD Q (p
      > 0.05) obtained from plots of V and Q against Log(V/Q) were found between normal
      subjects and subjects with a PE, but no correlation was found between either of
      these parameters and the degree of lung damage in subjects with a PE (p > 0.05).
      Whilst V/Q values were log normally distributed, the V/Q distributions from the
      subjects with a PE failed to show the bimodal distribution predicted from
      theoretical considerations and MIGET measurements previously reported. There was
      a statistically significant difference in the mean and standard deviation values
      of the V/Q distributions between normal subject and subjects with a PE (p < 0.05)
      but not in the median values (p > 0.05). There was no correlation between the
      mean, median and standard deviation of the distributions from the subjects with a
      PE and the percentage of damage present (p > 0.05).

PMID- 18057512
TI  - Optimal designs for studying bioimpedance.
AB  - D-optimal designs for nonlinear fixed and mixed effects models are explored, and
      the theory is applied to the measurement and analysis of bioelectrical impedance.
      Bioimpedance is known to vary more at extreme frequencies than others. D-optimal
      designs that account for this variation, and also possible mis-specification of
      initial parameter estimates, are considered in an attempt to find designs that
      will provide good parameter estimates in practice.

PMID- 18057513
TI  - Effect of missing RR-interval data on heart rate variability analysis in the time
      domain.
AB  - In this study, the effects of missing RR-interval data on time-domain analysis
      were investigated using simulated missing data in real RR-interval tachograms and
      actual missing RR data in an ECG obtained by an unconstrained measurement. For
      the simulation, randomly selected data (0-100 s) were removed from real RR data
      obtained from the MIT-BIH normal sinus rhythm database. In all, 2615 tachograms
      of 5 min durations were used for this analysis. For certain durations of missing
      data, the analysis was performed by 1000 Monte Carlo runs. MeanNN, SDNN, SDSD,
      RMSSD and pNN50 were calculated as the time-domain parameters in each run, and
      the relative errors between the original and the incomplete tachograms for these
      parameters were computed. The results of the simulation revealed that MeanNN is
      the parameter most robust to missing data; this feature can be explained by the
      theory of finite population correction (FPC). pNN50 is the parameter most
      sensitive to missing data. MeanNN was also found to be the most robust to real
      missing RR data derived from a capacitive-coupled ECG recorded during sleep;
      furthermore, the parameter patterns for the missing data were considerably
      similar to those for the original RR data, although the relative errors may
      exceed those of the simulation results.

PMID- 18057514
TI  - Quantitative analysis of the relation between soft tissue stiffness palpated from
      the body surface and tissue hemodynamics in the human forearm.
AB  - We investigated the quantitative relation between soft tissue stiffness palpated
      from the body surface and hemodynamics in the human forearm. We examined the
      relation between pressures and blood flow in both the main artery and vein
      measured by magnetic resonance imaging (MRI), the cross-sectional area of forearm
      measured by MRI and soft tissue stiffness. Six male volunteers participated. Two
      tourniquet pressures, 120 mmHg and 230 mmHg, were used to induce an occlusion of
      the proximal portion of the upper arm. Measurements were made at the mid-belly of
      the brachioradial muscle. The venous outflow ceased at tourniquet pressures of
      120 and 230 mmHg. The arterial flow was interrupted at 230 mmHg. Larger increases
      of the cross-sectional area and soft tissue stiffness were found at 120 mmHg than
      at 230 mmHg. The increase of the cross-sectional area of muscle was larger than
      that of the surrounding connective tissue during occlusion. We propose that low
      pressure compression occludes venous outflow without restricting arterial inflow
      and induces an increase of the cross-sectional area that reflects the
      intramuscular pressure; and changes in this pressure caused by fluid accumulation
      should be the major factor for change in stiffness.

PMID- 18057515
TI  - Analysis of surface EMG signal morphology in Parkinson's disease.
AB  - A novel approach is presented for the analysis of surface electromyogram (EMG)
      morphology in Parkinson's disease (PD). The method is based on histogram and
      crossing rate (CR) analysis of the EMG signal. In the method, histograms and CR
      values are used as high-dimensional feature vectors. The dimensionality of them
      is then reduced using the Karhunen-Loeve transform (KLT). Finally, the
      discriminant analysis of feature vectors is performed in low-dimensional
      eigenspace. Histograms and CR values were chosen for analysis, because
      Parkinsonian EMG signals typically involve patterns of EMG bursts. Traditional
      methods of EMG amplitude and spectral analysis are not effective in analyzing
      impulse-like signals. The method, which was tested with EMG signals measured from
      25 patients with PD and 22 healthy controls, was promising for discriminating
      between these two groups of subjects. The ratio of correct discrimination by
      augmented KLT was 86% for the control group and 72% for the patient group. On the
      basis of these results, further studies are suggested in order to evaluate the
      usability of this method in early stage diagnostics of PD.

PMID- 18057516
TI  - An automatic identification and removal method for eye-blink artifacts in event
      related magnetoencephalographic measurements.
AB  - While measuring event-related magnetoencephalographic (MEG) signals using visual
      stimuli, eye blinks were inevitable and generated large magnetic artifacts. Since
      trials containing eye blinks were excluded from the analyses, the signal-to-noise
      ratio of the event-related signals was decreased. In this study, we propose a
      method to identify the eye blink magnetic artifacts and remove them automatically
      using independent component analysis preprocessed by principal component
      analysis. The method evaluates the spatiotemporal similarity between independent
      components and both MEG and electro-oculogram data based on a newly devised cost
      function. Testing of the method on event-related MEG signals measured by a 306
      channel whole-head system in a visual perception task led to the successful
      identification and removal of eye-blink artifacts in all trials containing eye
      blinks from all the seven subjects.

PMID- 18057517
TI  - An approach to in situ detection of hydrogen peroxide: application of a
      commercial needle-type electrode.
AB  - The reactive oxygen species are thought to play major roles in developing
      different physiological disorders. A commercial, needle-type amperometric glucose
      enzyme sensor manufactured for human patients was investigated. This sensor
      measures glucose by detecting hydrogen peroxide evolved in the enzymatic reaction
      of glucose. In the experiments, the immobilized enzyme layer of the sensor was
      inactivated. The applicability of this 'inhibited' glucose sensor for detecting
      hydrogen peroxide was tested. The simple battery powered, single purpose
      electronic unit was replaced by an advanced electrochemical workstation. The
      sensitivity, selectivity and lower limit of detection of the hydrogen peroxide
      measurements were investigated. Voltammetric measurements were carried out in
      intensively stirred buffered aqueous media, in plasma samples as well as in
      subcutan areas of anesthetized Wistar rats. Preliminary measurements carried out
      with the amperometric and periodically interrupted amperometric technique
      predicted that the human clinical sensor, after our enzyme inhibition step, can
      be used for checking the elevation of the hydrogen peroxide level in different
      subcutan areas of human subjects.

PMID- 18057518
TI  - The vulvalgesiometer as a device to measure genital pressure-pain threshold.
AB  - The construction and application of the vulvalgesiometer are described. This
      manually-applied device allows for the quantifiable measurement of pressure-pain
      thresholds in the external female genital region. A set of five vulvalgesiometers
      exerting pressures from 3 to 950 g was used in two studies. The goal of the first
      study was to examine the ability of the vulvalgesiometers to discriminate between
      women with and without provoked vestibulodynia (PVD). In a matched sample of
      affected and non-affected women, women with PVD exhibited significantly lower
      vestibular pressure-pain thresholds as compared to control women. As well,
      approximately half the sample of women with PVD described the sensation elicited
      at pressure-pain threshold as similar to the pain experienced during sexual
      intercourse. The goal of the second study was to investigate the inter-rater
      reliability of the vulvalgesiometers. In this separate sample of women with and
      without PVD, each participant was tested for pressure-pain threshold by two
      different investigators at different times. Results demonstrated high levels of
      inter-rater reliability, indicating that the vulvalgesiometers can be
      consistently used by different investigators. Further, results indicated
      significant negative correlations between pressure-pain thresholds and pain
      intensity ratings recorded during the cotton-swab test, suggesting that the lower
      the threshold, the higher the pain ratings during vestibular palpation. The
      vulvalgesiometers can be utilized for several purposes, including treatment
      outcome studies and measuring the degree of PVD severity.

PMID- 18057519
TI  - Non-genomic biomarkers of risk in ovarian cancer.

PMID- 18057520
TI  - Etiology and pathogenesis of epithelial ovarian cancer.
AB  - Ovarian cancer is complex disease composed of different histological grades and
      types. However, the underlying molecular mechanisms involved in the development
      of different phenotypes remain largely unknown. Epidemiological studies
      identified multiple exogenous and endogenous risk factors for ovarian cancer
      development. Among them, an inflammatory stromal microenvironment seems to play a
      critical role in the initiation of the disease. The interaction between such a
      microenvironment, genetic polymorphisms, and different epithelial components such
      as endosalpingiosis, endometriosis, and ovarian inclusion cyst in the ovarian
      cortex may induce different genetic changes identified in the epithelial
      component of different histological types of ovarian tumors. Genetic studies on
      different histological grades and types provide insight into the pathogenetic
      pathways for the development of different disease phenotypes. However, the link
      between all these genetic changes and the etiological factors remains to be
      established.

PMID- 18057521
TI  - The continuum of serous tumors of low malignant potential and low-grade serous
      carcinomas of the ovary.
AB  - The role of serous tumors of low malignant potential (LMP) in the development of
      invasive epithelial cancer of the ovary is debatable. This review summarizes the
      current clinical, genetic, and genomic evidence for the existence of a continuum
      comprising both LMP serous tumors and low-grade serous ovarian carcinomas.

PMID- 18057522
TI  - Biomarkers of mucinous tumors of the ovary.

PMID- 18057523
TI  - Early detection of ovarian cancer.
AB  - Despite advances in therapy, ovarian cancer remains the most deadly of the
      gynecological cancers. Less than 30% of women with advanced stage disease survive
      long-term. When diagnosed in stage I, up to 90% of patients can be cured with
      conventional surgery and chemotherapy. At present, only 25% of ovarian cancers
      are detected in stage I due, in part, to the absence of specific symptoms and to
      lack of an effective screening strategy. Early detection of ovarian cancer might
      significantly improve the overall survival rate of women with ovarian cancer if
      1) most cancers are clonal and unifocal, arising in the ovary rather than in the
      peritoneum, 2) metastatic disease results from progression of clinically
      detectable stage I lesions, and 3) cancers remain localized for a sufficient
      interval to permit cost-effective screening. Given the prevalence of ovarian
      cancer, strategies for early detection must have high sensitivity for early stage
      disease (> 75%), but must have extremely high specificity (99.6%) to attain a
      positive predictive value of at least 10%. Transvaginal sonography (TVS), serum
      markers and a combination of the two modalities have been evaluated for early
      detection of ovarian cancer. Among the serum markers, CA125 has received the most
      attention, but lacks the sensitivity or specificity to function alone as a
      screening test. Greater specificity can be achieved by combining CA125 and TVS
      and/or by monitoring CA125 over time. Two stage screening strategies promise to
      be cost effective, where abnormal serum assays prompt TVS to detect lesions that
      require laparotomy. Accrual has been completed for a 200,000 woman trial in the
      United Kingdom that will test the ability of a rising CA125 to trigger TVS and
      subsequent exploratory surgery. Given the heterogeneity of ovarian cancer, it is
      unlikely that any single marker will be sufficiently sensitive to provide an
      effective initial screen. Sensitivity of serum assays might be enhanced by
      utilizing a panel of biomarkers. Candidate biomarkers have been discovered
      through empirical development of monoclonal antibodies, studies of gene
      expression, cloning of gene families and proteomic techniques. The development of
      technologies that measure multiple serum markers simultaneously, linked to the
      creation of statistical methods that enhance sensitivity without sacrificing
      specificity hold great promise.

PMID- 18057524
TI  - Proteomics as a tool for biomarker discovery.
AB  - Novel technologies are now being advanced for the purpose of identification and
      validation of new disease biomarkers. A reliable and useful clinical biomarker
      must a) come from a readily attainable source, such as blood or urine, b) have
      sufficient sensitivity to correctly identify affected individuals, c) have
      sufficient specificity to avoid incorrect labeling of unaffected persons, and d)
      result in a notable benefit for the patient through intervention, such as
      survival or life quality improvement. Despite these critical descriptors, the few
      available FDA-approved biomarkers for cancer do not completely fit this
      definition and their benefits are limited to a small number of cancers. Ovarian
      cancer exemplifies the need for a diagnostic biomarker of early stage disease.
      Symptoms are present but not specific to the disease, delaying diagnosis until an
      advanced and generally incurable stage in over 70% of affected women. As such,
      diagnostic intervention in the form of oopherectomy can be performed in the
      appropriate at-risk population if identified such as with a new accurate,
      sensitive, and specific biomarker. If early stage disease is identified, the
      requirement for survival and life quality improvement will be met. One of the new
      technologies applied to biomarker discovery is tour-de-force analysis of serum
      peptides and proteins. Optimization of mass spectrometry techniques coupled with
      advanced bioinformatics approaches has yielded informative biomarker signatures
      discriminating presence of cancer from unaffected in multiple studies from
      different groups. Validation and randomized outcome studies are needed to
      determine the true value of these new biomarkers in early diagnosis, and improved
      survival and quality of life.

PMID- 18057525
TI  - Markers of angiogenesis in ovarian cancer.
AB  - Tumor development and progression are inherently dependent on the process of
      angiogenesis. Recently, anti-angiogenic therapy has started to show promise as an
      effective treatment strategy in many solid tumors including ovarian carcinoma.
      Unfortunately, lack of effective biomarkers presents a challenge for oncologists
      in treatment planning as well as monitoring response of new anti-vascular agents.
      Previously, quantification of angiogenesis by microvessel density analysis
      provided useful prognostic information, however, its utility following anti
      angiogenic therapy remains to be determined. Moreover, since secreted cytokines
      play an active part in angiogenesis by mediating neovascularization in tumors,
      investigations have focused on their potential role to serve as candidate
      biomarkers of disease detection, prognosis, and treatment response. In this
      article, we review the role of key angiogenesis markers as potential biomarkers
      in ovarian carcinoma.

PMID- 18057526
TI  - Cell cycle and related protein.

PMID- 18057527
TI  - Immune prognostic factors in ovarian cancer: lessons from translational research.

PMID- 18057528
TI  - Claudin proteins in ovarian cancer.
AB  - Members of the claudin family of tight junction proteins have been found altered
      in several malignancies, including ovarian cancer. Because claudin-3 and -4 are
      elevated in the vast majority of ovarian tumors, they may represent useful
      biomarkers for detection and prognosis, as well as ideal targets for therapy
      using the Clostridium perfringens enterotoxin.

PMID- 18057529
TI  - Utilizing virtual microscopy for quality control review.

PMID- 18057530
TI  - Circulating VEGF as a biological marker in patients with rheumatoid arthritis?
      Preanalytical and biological variability in healthy persons and in patients.
AB  - BACKGROUND: Soluble vascular endothelial growth factor (VEGF) is a promising
      biomarker in monitoring rheumatoid arthritis (RA), but studies of pre-analytical
      and biologic variability are few. METHODS: VEGF was measured by ELISA methods in
      serum and plasma from healthy persons and RA patients. Pre-analytical factors
      were investigated. A reference interval for VEGF was established in serum and
      plasma from 306 healthy persons. Diurnal, day-to-day, week-to-week, long-term
      variability, and impact of exercise were evaluated. RESULTS: Delayed processing
      time, room temperature, low centrifugal force and contamination of plasma with
      cellular elements lead to significant increases in VEGF levels, whereas storage
      for up to 2 years at -80 degrees C or up to 10 freeze/thaw cycles did not affect
      VEGF levels. Serum VEGF levels were 7-10 fold higher than plasma VEGF levels.
      Reference intervals for VEGF (plasma: 45 pg/ml (range: non-detectable to 352);
      serum: 328 pg/ml (53-1791)) were independent of gender and age. Short- and long
      term biologic variability included diurnal variation (sampling should take place
      after 7 AM) and impact of exercise (increased VEGF immediately after bicycling
      normalised within 1 hour). CONCLUSIONS: Pre-analytical factors and biologic
      variability including diurnal variation and impact of exercise should be
      accounted for in future studies that include circulating VEGF as a biological
      marker.

PMID- 18057531
TI  - Homogeneous assay of rs4343, an ACE I/D proxy, and an analysis in the British
      Women's Heart and Health Study (BWHHS).
AB  - Current literature suggests that ACE SNP rs4343, ACE 2350A>G in exon 17, T202T,
      may be the best proxy for the ACE Alu I/D whereas rs4363 and rs4362 may be
      slightly stronger predictors of ACE levels. Considering reported difficulties in
      genotyping ACE I/D and stronger associations of rs4343 than ACE I/D with plasma
      ACE levels in Africans, and suitability of rs4343 for allelic mRNA (cDNA)
      studies, we developed and validated a liquid phase assay for rs4343, which has
      advantage on both functional and technical grounds. We confirmed that rs4343, is
      in near perfect linkage disequilibrium (D'=1, r2=0.88, n=64) with ACE I/D in
      Europeans (A and G alleles of rs4343 marking insertion and deletion alleles of
      ACE I/D respectively). We then studied its association with metabolic and
      cardiovascular traits in 3253 British women (60-79 years old). Apart from a
      nominal trend of association with diastolic blood pressure (p anova=0.08; p
      trend=0.05), no other associations were observed. A post-hoc vascular and general
      phenome scan revealed no further associations. We conclude that ACE I/D is not a
      major determinant of metabolic and cardiovascular traits in this population.
      Liquid phase genotyping of SNP rs4343 may be preferable to gel based ACE I/D
      genotyping both for technical and functional reasons.

PMID- 18057532
TI  - MTHFR genetic polymorphism as a risk factor in Egyptian mothers with Down
      syndrome children.
AB  - Recent reports linking Down syndrome (DS) to maternal polymorphisms at the
      methylenetetrahydrofolate reductase (MTHFR) gene locus have generated great
      interest among investigators in the field. The present study aimed at evaluation
      of MTHFR 677C/T and 1298A/C polymorphisms in the MTHFR gene as maternal risk
      factors for DS. Forty two mothers of proven DS outcomes and forty eight control
      mothers with normal offspring were included. Complete medical and nutritional
      histories for all mothers were taken with special emphasis on folate intake.
      Folic acid intake from food or vitamin supplements was significantly low (below
      the Recommended Daily Allowance) in the group of case mothers compared to control
      mothers. Frequencies of MTHFR 677T and MTHFR 1298C alleles were significantly
      higher among case mothers (32.1% and 57.1%, respectively) compared to control
      mothers (18.7% and 32.3%, respectively). Heterozygous and homozygous genotype
      frequencies of MTHFR at position 677 (CT and TT) were higher among case mothers
      than controls (40.5% versus 25% and 11.9% versus 6.2%, respectively) with an odds
      ratio of 2.34 (95% confidence interval [CI] 0.93-5.89) and 2.75 (95% CI 0.95
      12.77), respectively. Interestingly, the homozygous genotype frequency (CC) at
      position 1298 was significantly higher in case mothers than in controls (33.3%
      versus 2.1% respectively) with an odds ratio of 31.5 (95% CI 3.51 to 282.33)
      indicating that this polymorphism may have more genetic impact than 677
      polymorphism. Heterozygous genotype (AC) did not show significant difference
      between the two groups. We here report on the first pilot study of the possible
      genetic association between DS and MTHFR 1298A/C genotypes among Egyptians.
      Further extended studies are recommended to confirm the present work.

PMID- 18057533
TI  - Expression of MAGE-A12 in oral squamous cell carcinoma.
AB  - Melanoma associated-A antigens (MAGE-A) are silent in normal tissues except
      testis. However, they are activated ina variety of different tumors. Thus, their
      expression is highly specific to cancer cells. Reverse transcription-nested
      polymerase chain reaction (RT-nPCR) is a highly sensitive technique that has been
      used successfully for the detection of MAGE genes in tissue samples. The aim of
      the study is to analyze the expression rate of MAGE-A12 in oral squamous cell
      carcinoma (OSCC) using a high sensitive RT-nPCR. Total of 57 tissue samples
      obtained from patients with OSCC and 20 normal oral mucosal (NOM) probes of
      otherwise healthy volunteers were included to this study. No expression of MAGE
      A12 was observed in the non-neoplasticNOM tissues. MAGE-A12 was expressed in
      49.1% of the investigated tumor samples. The correlation between malignant lesion
      and MAGE-A12 detection was significant (p<0.001). It is concluded that results of
      this study may indicate MAGE-A12 asa useful additional diagnostic marker
      especially for the early detection of OSCC distinguishing neoplastic
      transformation and detection of occult and/or rare disseminated cancer cells. In
      addition, MAGE-A12 expression in OSCC may also determine anew immunotherapeutic
      target and might be warranted to develop vaccine for OSCC

PMID- 18057534
TI  - Erythrocyte aggregation as an early biomarker in patients with asymptomatic
      carotid stenosis.
AB  - BACKGROUND: Atherosclerosis is a chronic inflammatory disease. DESIGN: We have
      evaluated the degree of erythrocyte aggregation (EA) as a microinflammatory
      biomarker in a cohort of hospital-based, neurologically asymptomatic outpatients.
      METHODS: The degree of EA and carotid artery stenosis was evaluated in 510
      individuals by using a simple slide test and image analysis. RESULTS: Four
      hundred and sixteen individuals had minimal carotid stenosis (< 30%); 47 had mild
      to moderate stenosis (30-69%) and 47 had severe stenosis (> 70%). A significant
      correlation was noted between the degree of carotid stenosis and the erythrocyte
      sedimentation rate (ESR), white blood cell count (WBCC) and fibrinogen (r=0.160,
      p=0.005; r=0.191, p=0.001 and r=0.126, p=0.026, respectively). The significant
      correlation was noted between the degree of carotid stenosis and EA (r=0.209, p<
      0.001). The subjects with severe stenosis differed significantly from the other
      groups in their ESR, WBCC and EA. High sensitivity C-reactive protein (hs-CRP)
      concentrations did not discriminate between the presence and absence of
      significant carotid atherosclerotic disease. CONCLUSIONS: Inflammatory biomarkers
      such as ESR and the EA test are more sensitive than hs-CRP to the presence of a
      significant atherosclerotic carotid burden. These biomarkers might aid in the
      detection and quantification of microinflammation in individuals with carotid
      atherosclerosis.

PMID- 18057535
TI  - GPR87 is an overexpressed G-protein coupled receptor in squamous cell carcinoma
      of the lung.
AB  - Lung cancer is the leading cause of cancer death worldwide. The overall 5-year
      survival after therapy is about 16% and there is a clear need for better
      treatment options, such as therapies targeting specific molecular structures. G
      protein coupled receptors (GPCRs), as the largest family of cell surface
      receptors, represent an important group of potential targets for diagnostics and
      therapy. We therefore used laser capture microdissection and GPCR-focused
      Affymetrix microarrays to examine the expression of 929 GPCR transcripts in
      tissue samples of 10 patients with squamous cell carcinoma and 7 with
      adenocarcinoma in order to identify novel targets in non-small cell lung
      carcinoma (NSCLC). The relative gene expression levels were calculated in tumour
      samples compared to samples of the neighbouring alveolar tissue in every patient.
      Based on this unique study design, we identified 5 significantly overexpressed
      GPCRs in squamous cell carcinoma, in the following decreasing order of
      expression: GPR87 > CMKOR1 > FZD10 > LGR4 > P2RY11. All are non-olfactory and
      GRAFS (glutamate, rhodopsin, adhesion, frizzled/taste2, secretin family)
      classified. GPR87, LGR4 and CMKOR1 are orphan receptors. GPR87 stands out as a
      candidate for further target validation due to its marked overexpression and
      correlation on a mutation-based level to squamous cell carcinoma.

PMID- 18057536
TI  - Association of Interleukin-10 gene promoter polymorphisms in Saudi patients with
      vitiligo.
AB  - The promoter region of human Interleukin -10 gene is highly polymorphic and has
      been associated with numerous autoimmune diseases. Recent studies have linked
      vitiligo with defective autoimmune system. This study is aimed to explore a
      possible association between IL-10 gene polymorphism and vitiligo in Saudi
      population. This case control study consisted of 184 Saudi subjects including 83
      vitiligo patients (40 males, 43 females mean age 27.85 +/- 12.43 years) and 101
      matched controls. Genomic DNA was extracted from the blood samples of healthy
      controls and Vitiligo patients visiting out patient clinic of Department of
      Dermatology, Riyadh Armed Forces Hospital, using QIA ampR DNA mini kit (Qiagen
      CA, USA). Interleukin-10 gene was amplified by polymerase chain reaction (PCR)
      using Arms primers to detect any polymorphism involved at positions -592, -819
      and -1082. The frequencies of GG genotype at -1082, and CC genotype at positions 
      592 and 819 were significantly higher in vitiligo patients compared to healthy
      subjects suggesting that GG and CC genotypes might be susceptible to vitiligo in
      Saudis. On the other hand genotypes -1082 GA, -819 CT, and -592 CA of IL-10 were
      more prevalent in healthy controls suggesting protective effects of GA, CT and CA
      genotypes against vitiligo. This study indicates that the IL-10 gene may play a
      significant role in the etiology of vitiligo among Saudis.

PMID- 18057537
TI  - Manganese superoxide dismutase gene polymorphism (V16A) is associated with
      diabetic retinopathy in Slovene (Caucasians) type 2 diabetes patients.
AB  - Substantial data indicate that oxidative stress is involved in the development of
      diabetic retinopathy. Two candidate genes that affect the oxidative stress are
      manganese mitochondrial superoxide dismutase (Mn-SOD) and endothelial nitric
      oxide synthase (eNOS). The aim of the present study was to examine the role of
      the V16A polymorphism of the Mn-SOD gene and the 4a/b polymorphism of the eNOS
      gene in the development of diabetic retinopathy in Caucasians with type 2
      diabetes. In this cross sectional case-control study 426 unrelated Slovene
      subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 283 patients
      with diabetic retinopathy and the control group of 143 subjects with type 2
      diabetes of duration of more than 10 years who had no clinical signs of diabetic
      retinopathy. A significantly higher frequency of the VV genotype of the V16A
      polymorphism of the Mn-SOD was found in patients with diabetic retinopathy
      compared to those without diabetic retinopathy (OR=2.1, 95% whereas the 4a/b
      polymorphism of the eNOS gene failed to yield an association with diabetic
      retinopathy. We may conclude that the VV genotype of the V16A polymorphism of the
      Mn-SOD gene was associated with diabetic retinopathy in Caucasians with type 2
      diabetes, therefore it might be used as a genetic marker of diabetic retinopathy
      in Caucasians.

PMID- 18057538
TI  - One medicine: an introduction.

PMID- 18057539
TI  - Comparative pathology of mammary gland cancers in domestic and wild animals.
AB  - Mammary cancer occurs among all taxonomic groups, and comparing the disease in
      animals with breast cancer in women could greatly improve our understanding of
      the relevant risk factors and genetic profiles for this disease. Differences in
      cancer prevalence between carnivores and herbivores and between captive and wild
      carnivores are striking and support the hypotheses that diet and reproductive
      history are major risk factors. Domestic dogs and cats have a high prevalence of
      mammary tumors, and the majority of tumors in cats are aggressive cancers. Many
      domestic dogs and cats are prevented from breeding, resulting in their being
      exposed to recurrent estrogen peaks followed by high persistent levels of
      progesterone. Therefore progesterone appears to be a significant risk factor for
      cancer development. Supporting this suspicion is the observation that most
      mammary cancers in zoo cats are in those treated with the potent synthetic
      progestin contraceptive, melengestrol acetate. The more common morphologic types
      of mammary cancer in canids and felids include tubulopapillary, solid,
      cribriform, comedo and anaplastic carcinomas. Dogs also develop complex
      carcinomas, which likely evolve from the complex adenomas or mixed tumors that
      are so common in this species and are promoted by exogenous progesterone
      treatment. Among zoo felids, jaguars are at higher risk for mammary cancer and
      also have a high prevalence of ovarian papillarycystadenocarcinomas, a profile
      similar to women with BRCA1 mutations. As for women, estrogen (ER) and
      progesterone receptor (PR) expression varies in canine and feline mammary
      cancers. In general, ER expression is low, but PR expression persists in most
      cancers. Alterations in molecular controls of cell proliferation or survival in
      breast cancer, such as cyclin A and p53 expression, have been identified in dog
      and cat mammary cancers. Overall, spontaneous mammary cancers in cats and dogs
      make excellent models for human breast cancer, and knowledge of mammary
      carcinogenesis would be greatly enhanced across all species by a "One Medicine"
      approach.

PMID- 18057540
TI  - Review of mammary gland neoplasia in nonhuman primates.

PMID- 18057541
TI  - Special considerations in mouse models of breast cancer.

PMID- 18057542
TI  - Comparing genetically engineered mouse mammary cancer models with human breast
      cancer by expression profiling.
AB  - Breast cancer is a heterogeneous disease, and much of the molecular basis for
      this heterogeneity is being unraveled using advanced genomic technologies. More
      recently, global transcriptional profiling has proven to be an effective new tool
      for characterizing human tumors. Genomic "signatures'' have been developed that
      classify tumors with varying prognoses and responses to treatment. Recent studies
      have begun to extend the use of global transcriptional profiling to better
      characterize genetically engineered mouse (GEM) models of breast cancer, which
      will improve the ability to translate basic research advances into clinical
      advances. GEM models of mammary carcinoma have proven to be invaluable tools to
      gain insight into mechanisms underlying tumor initiation, progression, and
      therapeutic responses in an in vivo system where tumors spontaneously develop in
      an appropriate tissue environment. This review will discuss the use of
      transcriptional profiling of breast cancer in tumors from both human patients and
      GEM models to improve prognostic measures, examine mechanisms of tumor initiation
      and progression, identify novel therapeutic targets, and improve pre-clinical
      testing for drug development. Together, these advances offer a framework for
      classifying human tumors, identifying appropriate GEM models for specific
      experimental purposes, and utilizing the combined data to identify more specific
      and effective cancer therapies.

PMID- 18057543
TI  - Genetically engineered rat models for breast cancer.
AB  - Rat mammary cancers generally resemble many features of human breast cancer. With
      the recent developments in rat genetic engineering, the rat has become an
      excellent model system to study aspects of the molecular etiology of breast
      cancer. In this review, we describe the efforts to generate genetically
      engineered rat models for breast cancer.

PMID- 18057544
TI  - Chemical carcinogenesis of rat and mouse mammary glands.
AB  - This review focuses on the comparative aspects of chemical carcinogenesis in the
      two major rodent species, rat and mouse, that have been used for the past 50
      years. The areas discussed are the similarities and differences in mammary
      tumorigenesis in response to similar chemical carcinogens, the strengths and
      weaknesses of each model and the usefulness of each model for understanding the
      cellular and molecular basis in the development and pathology of human breast
      cancer. Human breast cancer is a very heterogeneous disease and presents itself
      in many forms. One important lesson derived from the use of animal models is that
      each model serves to illuminate some aspect of human breast cancer and mimics a
      subset of the many subsets of human breast disease. Thus, many different models
      will be needed to fully enable an understanding of the cellular and molecular
      basis for human breast cancer and eventually provide the critical preventive and
      therapeutic approaches to conquer this cancer.

PMID- 18057545
TI  - The rat oncogenome: comparative genetics and genomics of rat models of mammary
      carcinogenesis.
AB  - The Norway rat has for many years been widely used as an experimental model for
      the study of breast cancer etiology and prevention. Mammary cancer can be induced
      in rats by a variety of agents. The mammary cancers that develop in the various
      rat models resemble in many respects the breast cancers that develop in humans.
      It is now clear that significant differences exist between different rat models
      with respect to the genetic bases of susceptibility to mammary cancer as well as
      the somatic genetic events that are associated with development of mammary
      cancer. In this review I summarize our current understanding of the genetic and
      genomics of mammary cancer in the rat, compare and contrast the genetic/genomic
      features of different rat mammary cancer models and discuss the relevance of
      these models to breast cancer in humans.

PMID- 18057546
TI  - Toxicogenomic analyses of genetic susceptibility to mammary gland carcinogenesis
      in rodents: implications for human breast cancer.
AB  - The Human Genome Project and the multitude of genomic technologies that it
      generated have dramatically altered the face of biological research. Genomic
      sequence information allowed for the development of high throughput technologies
      for DNA sequencing, gene expression profiling, genotyping, and detection of
      epigenetic changes. These technologies provide an unprecedented opportunity to
      elucidate how genetic variation and cellular responses to insult from environment
      toxicants and stressors, drugs, infections, co-morbid disease, and dietary
      factors among others, contribute to complex human diseases, including cancer.
      Toxicogenomics, which combines classical toxicology and genetics with the tools
      of modern genomics, promises to help elucidate and classify compounds based on
      mechanisms of toxicity, predict toxicity of untested compounds, provide improved
      screening and exposure monitoring, enhance the ability to predict toxicity and
      disease outcomes following exposure, and identify genetically susceptible
      individuals. Toxicogenomic data are therefore expected to do much to inform risk
      assessment. Rodents are excellent models for the study of the molecular and
      genetic bases for human disease, and are still used extensively to screen for
      toxic effects of drugs and environmental toxicants. In the present review, we
      explore how the combination of toxicogenomic approaches with rodent models can
      accelerate the discovery of human breast cancer susceptibility genes.

PMID- 18057547
TI  - Epilog: comparative medicine, one medicine and genomic pathology.
AB  - The study of breast cancer has involved comparative pathology since the 1890s.
      Molecular biology has allowed the detailed examination of human, mouse, and rat
      genomes. The genes that are associated with breast cancer in humans cause cancer
      in genetically modified mice and rats. Global genomic analyses demonstrate even
      broader genomic homologies. The pathology illustrates the principle of One
      Medicine. This issue examines these contributions and opens the way for the
      examination of other mammalian species. The development of a new discipline,
      Genomic Pathology, can now be anticipated.

PMID- 18057548
TI  - Possible involvement of queuine in regulation of cell proliferation.
AB  - An increase in cell number is one of the most prominent characteristics of cancer
      cells. This may be caused by an increase in cell proliferation or decrease in
      cell death. Queuine is one of the modified base which is found at first anticodon
      position of specific tRNAs. It is ubiquitously present throughout the living
      system except mycoplasma and yeast. The tRNAs of Q-family are completely modified
      to Q-tRNAs in terminally differentiated somatic cells, however hypomodification
      of Q-tRNA is closely associated with cell proliferation and malignancy. Queuine
      participates at various cellular functions such as regulation of cell
      proliferation, cell signaling and alteration in the expression of growth
      associated proto-oncogenes. Like other proto-oncogenes bcl2 is known to involve
      in cell survival by inhibiting apoptosis. Queuine or Q-tRNA is suggested to
      inhibit cell proliferation but the mechanism of regulation of cell proliferation
      by queuine or Q-tRNA is not well understood. Therefore, in the present study
      regulation in cell proliferation by queuine in vivo and in vitro as well as the
      expression of cell death regulatory protein Bcl2 are investigated. For this DLAT
      cancerous mouse, U87 cell line and HepG2 cell line are treated with different
      concentrations of queuine and the effect of queuine on cell proliferation and
      apoptosis are studied. The results indicate that queuine down regulates cell
      proliferation and expression of Bcl2 protein, suggesting that queuine promotes
      cell death and participates in the regulation of cell proliferation.

PMID- 18057549
TI  - A combination of soy isoflavone supplementation and exercise improves lipid
      profiles and protects antioxidant defense-systems against exercise-induced
      oxidative stress in ovariectomized rats.
AB  - Menopause is often accompanied with weight gain, metabolic lipid abnormalities,
      and oxidative stress. In this study, we investigated the combined effects of
      exercise and soy isoflavone supplementation on the lipid profiles and antioxidant
      capacities of ovariectomized rats. Twenty-five female Sprague-Dawley rats were
      divided into 5 groups: sham-operated, ovariectomized (OVX), OVX with exercise
      (OVX+EX), OVX with soy isoflavone supplementation (OVX+ISO), and OVX with both
      soy isoflavones and exercise (OVX+ISO+EX). After 12 weeks of intervention,
      antioxidant status was evaluated in collected blood samples by the ferric
      reducing ability of plasma (FRAP), glutathione (GSH) content, and sodium oxide
      dismutase (SOD) activity. DNA damage in the lymphocytes was determined using
      alkaline single-cell gel electrophoresis (the Comet assay). Although there were
      no significant differences in weight gain and food intake, weight gain was lower
      in OVX+EX, OVX+ISO, and OVX+ISO+EX than in OVX. OVX+EX, OVX+ISO, and OVX+ ISO+EX
      showed a significant decrease in total cholesterol, triglycerides, and LDL
      cholesterol compared to OVX. The soy isoflavone supplemented group had
      significantly increased FRAP values and GSH contents in contrast to no changes in
      the exercised group, whereas exercise markedly increased SOD activity and H2O2
      induced DNA tail length and tail moment. Exercise with soy isoflavone
      supplementation significantly increased FRAP values and had no difference on SOD
      activity, including DNA damage. These results demonstrate that a combined
      treatment of moderate exercise and soy isoflavone supplementation could exert a
      beneficial effect on weight control and lipid profiles, and offer protection from
      exercise-induced oxidative stress in postmenopausal women.

PMID- 18057550
TI  - Involvement of ligand occupancy in Insulin-like growth factor-I (IGF-I) induced
      cell growth in osteoblast like MC3T3-E1 cells.
AB  - Growth factors and matrix proteins regulate the proliferation and differentiation
      of osteoblasts. The insulin-like growth factor (IGF) system comprises IGF-I, IGF
      II, and six high-affinity IGF-binding proteins (IGFBPs). IGFs stimulate cell
      growth in many types of tissue; IGF-binding proteins regulate cellular actions
      and can affect cell growth. IGF-I is involved in differentiation, proliferation,
      and matrix formation in osteoblasts; IGFBP-5 is associated with the extracellular
      matrix (ECM) and can potentiate the actions of IGF-I. We investigated the effect
      of ECM proteins on the responses of MC3T3-E1 osteoblast cells to IGF-I and IGFBP
      5. In addition, because extracellular signal-regulated kinases 1 and 2 (Erk 1/2)
      affect cell growth, we evaluated the effects of IGFBP-5 on Erk 1/2
      phosphorylation in MC3T3-E1 cells. IGF-I caused an increase in IGFBP-5 expression
      in cultured MC3T3-E1 cells, and IGF-I plus IGFBP-5 significantly increased cell
      growth. Likewise, the addition of IGF-I and IGFBP-5 to cultured MC3T3-E1 cells
      increased the synthesis of the ECM proteins osteopontin (OPN) and thrombospondin
      1 (TSP-1), which can bind to alphaVbeta3 integrin receptors on the cell surface.
      By contrast, the addition of an antibody against ECM proteins inhibited the
      effects of OPN and TSP-1 on IGFBP-5 expression. The stimulatory effect of IGFBP-5
      was mediated via Erk 1/2 activation. These data suggest that IGFBP-5 regulates
      Erk 1/2 phosphorylation in cultured MC3T3-E1 cells via ECM proteins that may
      ultimately stimulate the growth of osteoblasts. We determined whether occupation
      of the alphaVbeta3 integrin receptor affects IGF-I receptor (IGF-IR)-mediated
      signaling and function in MC3T3-E1 osteoblast cells. Occupation of the
      alphaVbeta3 integrin receptor with ECM proteins induced IGF-I-stimulated IGF-IR
      phosphorylation. Conversely, in the presence of the alphaVbeta3-specific
      disintegrin echistatin, IGF-I-stimulated IGF-IR activation was inhibited. IGF-I
      stimulated IGF-IR phosphorylation was accompanied by IRS-1 phosphorylation and
      MAPK activation. However, these effects were attenuated by echistatin. Thus,
      occupancy of the alphaVbeta3 disintegrin receptor modulates IGF-I-induced IGF-IR
      activation and IGF-IR-mediated function in MC 3T3-E1 osteoblasts.

PMID- 18057551
TI  - Diabetes, metallothionein, and zinc interactions: a review.
AB  - Epidemiological evidence, associating diabetes with zinc (Zn) deficiencies, has
      resulted in numerous research studies describing the effects of Zn and associated
      metallothionein (MT), on reducing diabetic complications associated with
      oxidative stress. MT has been found to have a profound effect on the reduction of
      oxidative stress induced by the diabetic condition. Over expression of MT in
      various metabolic organs has also been shown to reduce hyperglycaemia-induced
      oxidative stress, organ specific diabetic complications, and DNA damage in
      diabetic experimental animals, which have been further substantiated by the
      results from MT-knockout mice. Additionally, supplementation with Zn has been
      shown to induce in vivo MT synthesis in experimental animals and to reduce
      diabetes related complications in both humans and animal models. Although the
      results are promising, some caution regarding this topic is however necessary,
      due to the fact that the majority of the studies done have been animal based.
      Hence more human intervention trials are needed regarding the positive effects of
      MT and Zn before firm conclusions can be made regarding their use in the
      treatment of diabetes.

PMID- 18057552
TI  - Antidiabetic zinc(II)-N-acetyl-L-cysteine complex: evaluations of in vitro
      insulinomimetic and in vivo blood glucose-lowering activities.
AB  - The diabetic state is known to induce oxidative stress in its mechanism, which in
      turn is responsible for the complications of diabetes mellitus (DM). Recently, we
      found that Zn(II) complexes have in vitro insulinomimetic and in vivo blood
      glucose-lowering activities. During our study on the development of new Zn(II)
      complexes with antioxidative ligands involving L-cysteine, L-cysteine
      methylester, and N-acetyl-L-cysteine (nac), we found a new (N-acetyl-L
      cysteinato)Zn(II) (Zn(nac)) complex by evaluating of both its in vitro
      insulinomimetic and in vivo potencies. The insulinomimetic activity of Zn(nac)
      with respect to the inhibition of free fatty acid release in isolated rat
      adipocytes treated with epinephrine was higher than that of a well-known
      insulinomimetic VOSO4, being equivalent to that of ZnSO4. The blood glucose level
      of hyperglycemic KK-Ay mice with type 2 DM was reduced by daily intraperitoneal
      injections of Zn(nac) for 28 days. Their serum insulin, HbA1c, TCHO, and UN
      levels were remarkably decreased, indicating that Zn(nac) improved the insulin
      resistance of the mice. The improvement of DM by Zn(nac) was also confirmed by
      the oral glucose tolerance test. In conclusion, Zn(nac) complex is proposed to
      attenuate both hyperglycemia and hyperinsulinemia in KK-Ay mice by decreasing
      serum insulin, HbA1c, UN, and TCHO levels.

PMID- 18057554
TI  - Interleukin-8 gene polymorphism -251T>A and Alzheimer's disease.

PMID- 18057553
TI  - Apoptotic death induces Abeta production and fibril formation to a much larger
      extent than necrotic-like death in CGNs.
AB  - In this study we report that apoptotic death of primary cultures of cerebellar
      granule neurons is accompanied by release of thioflavin-binding proteins -
      indicative of the presence of beta-sheet structures - and fibril formation in the
      culture medium. When the same neurons are subjected to an excytotoxic death
      caused by 100 microM glutamate exposure, the amount of thioflavin binding is
      markedly reduced. Western blot analysis shows that fibrils contain monomers,
      dimers and trimers of amyloid-beta (Abeta) which, when observed at the electron
      microscope, have morphologies reminiscent of fibrils of senile plaques. These
      findings demonstrate that triggering an apoptotic pathway leads to beta-sheet
      transition and fibril formation of a protein primarily involved in Alzheimer's
      disease and may be of direct relevance to the possible link between apoptosis and
      this neuropathology.

PMID- 18057555
TI  - Bcl-2 overexpression protects against amyloid-beta and prion toxicity in GT1-7
      neural cells.
AB  - In this study we analysed the effect of Bcl-2 on the cytotoxicity induced by the
      amyloid-beta (Abeta(25-35)) and prion (PrP(106-126)) peptides by using GT1-7puro
      and GT1-7bcl-2 (overexpressing the anti-apoptotic protein Bcl-2) neural cells.
      Exposure to Abeta(25-35) (1-5 microM) and PrP(106-126) (25 microM) caused a
      decrease in cell viability, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. These data were correlated with Abeta(25
      35) and PrP(106-126)-induced activation of caspase-9, which is linked to the
      mitochondrial death pathway, and the activation of the effector caspase-3,
      suggesting cell death by apoptosis. Furthermore, Bcl-2 overexpression protected
      from loss of cell viability and caspase-9 and -3 activation induced by Abeta(25
      35) and PrP(106-126), showing that Bcl-2 is neuroprotective against apoptotic
      cell death caused by amyloidogenic peptides.

PMID- 18057556
TI  - Increased neurogenesis in young transgenic mice overexpressing human APP(Sw,
      Ind).
AB  - APP overexpressing mice have been widely used in the study of Alzheimer's disease
      (AD), focusing mainly at older ages, with higher accumulation of amyloid-beta
      peptide (Abeta). A decrease in hippocampal adult neurogenesis has been described
      in these models and proposed to be a consequence of Abeta accumulation. Only one
      study demonstrates increased neurogenesis in the hippocampus of APP
      overexpressing J20 mice, and suggests it is a compensatory effect due to a subtle
      Abeta-induced damage. We have previously reported that a specific aggregation of
      Abeta has neurogenic potential on neural stem cells (NSC) in vitro. In order to
      clarify the contradicting data reported in vivo, we investigated NSC
      proliferation and neuronal differentiation in the hippocampi of J20 mice at a
      broader range of ages. Using immunohistochemistry, we show increased
      proliferation and neuronal differentiation in the hippocampi of 3 month-old J20
      mice that reverted when animals became older. The increase in neurogenesis
      correlated with detectable levels of oligomeric Abeta, measured by ELISA and
      western blot. We suggest that oligomeric Abeta directly induces neurogenesis in
      vivo as has been demonstrated in vitro. Understanding the mechanisms underlying
      these changes could lead to treatments to control the neuronal differentiation of
      endogenous precursors through the progress of AD.

PMID- 18057557
TI  - Mercaptopropionaldehyde from homocysteine: implications for Alzheimer's disease.
AB  - There has been evidence for a causal relationship between homocysteine and
      Alzheimer's disease for several years but the mechanism is unclear. In vivo, some
      homocysteine is converted to the thiolactone. This report describes a novel
      reaction between homocysteine thiolactone and dehydroascorbic acid in which the
      homocysteine thiolactone is converted to 3-mercaptopropionaldehyde. This product
      is shown to react with proteins causing their precipitation (probably by cross
      linking). The two reactions are extremely facile and appear to be physiologically
      compatible suggesting a mechanism by which homocysteine may promote the
      deposition of proteins in nerve cells as amyloid plaques and fibrillary tangles.

PMID- 18057558
TI  - Serotonin transporter gene polymorphism and BPSD in mild Alzheimer's disease.
AB  - The purpose of the present study was to confirm an association of functional
      polymorphism within the serotonin transporter (5-HTT) gene with Alzheimer's
      disease (AD) and behavioral and psychological symptoms of dementia (BPSD) in mild
      AD. Apolipoprotein E (ApoE) gene polymorphism and 2 types of functional
      polymorphism in the 5-HTT gene, 5-HTT-linked polymorphic region (5-HTTLPR) and a
      5-HTT variable number of tandem repeats sequence (5-HTTVNTR) were analyzed
      longitudinally in outpatients with mild AD to find out whether there was a
      relation between any such polymorphisms and the occurrence of BPSD. No
      significant differences in genotype distribution or allele frequencies were
      identified for 5-HTTLPR or 5-HTTVNTR between AD patients and age- and sex-matched
      non-demented controls regardless of ApoE epsilon4 allele. No significant
      differences were noted in 5-HTTLPR genotype or allele distributions between AD
      patients with or without BPSD. However, significant associations were observed
      between presence of 5-HTTVNTR allele 10 and BPSD or aggressiveness. This
      difference was independent of the presence of the ApoE epsilon4 allele. As a
      result, 5-HTT polymorphisms are unlikely to play any substantial role in
      susceptibility to AD. Conversely, 5-HTTVNTR influences the risk of developing
      BPSD or aggressiveness and genetic variations in the 5-HTT gene may be involved
      in the development of symptomatology for mild AD.

PMID- 18057559
TI  - Intra-individual stability of CSF biomarkers for Alzheimer's disease over two
      years.
AB  - This study examines the intra-individual stability of cerebrospinal fluid (CSF)
      biomarkers for Alzheimer's disease (AD) over 2 years in 83 patients with mild
      cognitive impairment (MCI) and 17 cognitively healthy control individuals. All
      participants underwent clinical and neuropsychological evaluation and lumbar
      puncture at baseline and after 2 years at a university hospital memory clinic.
      CSF was analyzed for total tau (T-tau), phospho-tau(181) (P-tau(181)) and amyloid
      beta(1-42) (Abeta(1-42)). During the 2-year observational time, 12 MCI patients
      progressed to AD and 3 progressed to vascular dementia, while 68 remained stable.
      Baseline T-tau and P-tau(181) levels were elevated in the MCI-AD group as
      compared to the stable MCI patients and the control group (p<0.01), while
      baseline Abeta(1-42) levels were lower (p<0.001). Stable MCI patients were
      biochemically indistinguishable from controls. The biomarker levels at baseline
      and after 2 years showed Pearson R values between 0.81 and 0.91 (p<0.001) and
      coefficients of variation of 7.2 to 8.7%. In conclusion, intra-individual
      biomarker levels are remarkably stable over 2 years. Thus, even minor biochemical
      changes induced by treatment against AD should be detectable using these
      biomarkers, which bodes well for their usefulness as surrogate markers for drug
      efficacy in clinical trials.

PMID- 18057560
TI  - Binding of proteases to fibrillar amyloid-beta protein and its inhibition by
      Congo red.
AB  - Fibrillar amyloid-beta protein (fAbeta) is the principal component of amyloid
      plaques in the brains of patients with Alzheimer's disease (AD). We have recently
      reported that activity of trypsin is inhibited by fAbeta and that trypsin can
      bind to fAbeta. Neprilysin and insulysin are important proteases for the
      clearance of soluble Abeta. Here, we report that fAbeta also binds to neprilysin
      and insulysin, which results in the inhibition of their proteolytic activities.
      These findings suggest that clearance of soluble Abeta may be defective in AD
      because of binding of proteases to amyloid plaques, leading to inactivation of
      proteases that are required for catabolism of Abeta. The identification of
      compounds that can inhibit binding of proteases to fAbeta may, therefore, be of
      significance for therapeutic intervention in AD. Congo red and Thioflavin T are
      widely used for histopathological examination of amyloid plaques because of their
      strong affinity to fibrillar amyloid proteins. We examined the effect of Congo
      red and Thioflavin T (potent fAbeta-binding compounds) on the binding of
      different proteases to fAbeta. While Congo red inhibited the binding of trypsin,
      neprilysin and insulysin to fAbeta, Thioflavin T did not have any effect. The
      effect of Congo red was concentration-dependent and the inhibitory effect was in
      the order of trypsin > insulysin > neprilysin. When the effect of prebound-Congo
      red to fAbeta was examined, trypsin was unable to bind to this complex suggesting
      that Congo red may have better affinity than trypsin for binding to fAbeta. Based
      on these results, we propose that the inhibition of binding of proteases to
      amyloid plaques may help in reducing the deposition of Abeta in AD.

PMID- 18057561
TI  - Under-expression of Kalirin-7 Increases iNOS activity in cultured cells and
      correlates to elevated iNOS activity in Alzheimer's disease hippocampus.
AB  - Recently, it has been reported that Kalirin gene transcripts are under-expressed
      in AD hippocampal specimens compared to the controls. The Kalirin gene generates
      a dozen Kalirin isoforms. Kalirin-7 is the predominant protein expressed in the
      adult brain and plays crucial roles in growth and maintenance of neurons. Yet its
      role in human diseases is unknown. We report that Kalirin-7 is significantly
      diminished both at the mRNA and protein levels in the hippocampus specimens from
      19 AD patients compared to the specimens from 15 controls. Kalirin-7 associates
      with iNOS in the hippocampus, and therefore, Kalirin-7 is complexed with iNOS
      less in AD hippocampus extracts than in control hippocampus extracts. In cultured
      cells, Kalirin-7 associates with iNOS and down-regulates the enzyme activity. The
      down-regulation is attributed to the highly conserved 33 amino acid sequence,
      K(617) -H(649), of the 1,663 amino acids long Kalirin-7. Remarkably, the iNOS
      activity is considerably higher in the hippocampus specimens from AD patients
      than the specimens from 15 controls. These observations suggest that the under
      expression of Kalirin-7 in AD hippocampus correlates to the elevated iNOS
      activity.

PMID- 18057562
TI  - A method for a mechanical characterisation of human gluteal tissue.
AB  - The most common complication associated with immobilization is pressure sores
      caused by sustained localized tissue strain and stress. Computational simulations
      have provided insight into tissue stress-strain distribution, subject to loading
      conditions. In the simulation process, adequate soft tissue material parameters
      are indispensable. An in vivo procedure to characterise material parameters of
      human gluteal skin/fat and muscle tissue has been developed. It employs a
      magnetic resonance imaging (MRI) device together with an MRI compatible loading
      device. Using the derived data as constraints in an iterative optimization
      process the inverse finite element (FE) method was applied. FE-models were built
      and the material constants describing skin/fat and muscle tissue were
      parameterized and optimized. Separate parameter sets for human gluteal skin/fat
      and muscle were established. The long-term shear modulus for human gluteal
      skin/fat was G_{infinity, S/F}= 1182 Pa and for muscle G_{infinity, M} = 1025 Pa.
      The Ogden form for slightly compressible materials was chosen to define passive
      human gluteal soft tissue material behaviour. To verify the approach, the human
      skin/fat-muscle tissue compound was simulated using the derived material
      parameter sets and the simulation result was compared to empirical values. A
      correlation factor of R;{2} = 0.997 was achieved.

PMID- 18057563
TI  - The influence of quality criteria on parents' evaluation of medical web-pages: an
      Italian randomised trial.
AB  - The aim of this study is to verify the usefulness for parents of a web evaluation
      framework composed of ten quality criteria to improve their ability to assess the
      quality level of medical web sites. We conducted a randomised controlled trial
      that included two groups of parents who independently evaluated five paediatric
      web sites by filling out two distinct questionnaires: group A with the evaluation
      framework, group B without it. 40 volunteers were recruited from parents
      referring to the General Paediatrics Out-patients Department who satisfied the
      following eligibility criteria: Internet users, at least 1 child under 12 months
      old, no professional skill in Internet and medicine. The survey was taken between
      February 2, 2000 and March 22, 2000. Parents evaluated each web site and assigned
      a score, compared with a gold standard created by a group of experts. Suggesting
      evaluation criteria to parents seem useful for an improvement of their ability to
      evaluate web sites.

PMID- 18057564
TI  - Reference marker stability in computer aided orthopedic surgery: a biomechanical
      study in artificial bone and cadavers.
AB  - INTRODUCTION: In computer assisted orthopaedic surgery, rigid fixation of the
      Reference Marker (RM) system is essential for reliable computer guidance. A
      minimum shift of the RM can lead to substantial registration errors and
      inaccuracies in the navigation process. Various types of RM systems are available
      but there is little information regarding the relative stabilities of these
      systems. The aim of this study was to test the rotational stability of three
      commonly used RM systems. MATERIALS AND METHODS: One hundred and thirty Synbones
      and 15 cadavers were used to test the rotational stability of three different RM
      systems (Schanz' screw, RM B and RM C adjustment systems). Using a specially
      developed testing device, the peak torque sustained by each RM system was
      assessed in various anatomical sites. RESULTS: Comparison of means for Synbone
      showed that the RM C was the most stable (mean peak torque 5.60 +/- 1.21 Nm)
      followed by the RM B system (2.53 +/- 0.53 Nm) and the RM A (0.77 +/- 0.39 Nm)
      (p<0.01). The order of stability in relation to anatomical site was femoral
      shaft, distal femur, tibial shaft, proximal tibia, anterior superior iliac spine,
      iliac crest and talus. Results from the cadaver experiments showed similar
      results. Bi-cortical fixation was superior to mono-cortical fixation in the femur
      (p<0.01) but not the tibia (p=0.22). CONCLUSION: The RM system is the vital link
      between bone and computer and as such the stability of the RM is paramount to the
      accuracy of the navigation process. In choosing RM systems for computer navigated
      surgery surgeons should be aware of their relative stability. Anatomical site of
      RM placement also affect the stability. Mono-cortical fixation is generally less
      stable than bi-cortical.

PMID- 18057565
TI  - Dynamic iso-resistive trunk extension simulation: contributions of the intrinsic
      and reflexive mechanisms to spinal stability.
AB  - The effects of external resistance on the recruitment of trunk muscles and the
      role of intrinsic and reflexive mechanisms to ensure the spinal stability are
      significant issues in spinal biomechanics. A computational model of spine under
      the control of 48 anatomically oriented muscle actions was used to simulate iso
      resistive trunk movements. Neural excitation of muscles was attained based on
      inverse dynamics approach along with the stability-based optimization. The effect
      of muscle spindle reflex response on the trunk movement stability was evaluated
      upon the application of a perturbation moment. In this study, the trunk extension
      movement at various resistance levels while extending from 60 degrees flexion to
      the upright posture was investigated. Incorporation of the stability condition as
      an additional constraint in the optimization algorithm increased antagonistic
      activities for all resistance levels demonstrating that the co-activation caused
      an increase in the intrinsic stiffness of the spine and its stability in a feed
      forward manner. During the acceleration phase of the movement, extensors activity
      increased while flexors activity decreased in response to the higher resistance.
      The co-activation ratio noticed in the braking phase of the movement increased
      with higher resistance. In presence of a 30 Nm flexion perturbation moment,
      reflexive feed-back noticeably decreased the induced deviation of the velocity
      and position profiles from the desired ones at all resistance levels. The
      stability-generated co-activation decreased the reflexive response of muscle
      spindles to the perturbation demonstrating that both intrinsic and reflexive
      mechanisms contribute to the trunk stability. The rise in muscle co-activation
      can ameliorate the corruption of afferent neural sensory system at the expense of
      higher loading of the spine.

PMID- 18057567
TI  - Using the International Classification of Functioning, Disability and Health
      (ICF) in job placement.
AB  - The International Classification of Functioning, Disability and Health (ICF)
      presents a new paradigm for understanding health and health-related conditions
      and promises to be a useful tool in job placement. The ICF framework is
      compatible with ecological, systems-based approaches to placement and can assist
      vocational rehabilitation professionals in identifying needed interventions,
      implementing effective placement strategies, and assessing employment outcomes.
      This article presents an overview of the ICF, its potential applications in job
      placement practice and research, and provides a case study example. Current
      limitations of the ICF and possible future directions are also discussed.

PMID- 18057566
TI  - A pilot study to evaluate self initiated computer patient education in children
      with acute asthma in pediatric emergency department.
AB  - OBJECTIVE: The goal of the study was to investigate the feasibility and
      acceptance of an interactive computer assisted asthma education program in the
      pediatric emergency department (ED) for children with acute asthma exacerbations.
      METHODS: A pre-post non- randomized study was designed for children age 3 to 18
      years at the University of Maryland Hospital for Children, Baltimore. An
      interactive computer-assisted educational program, Patient Education and
      Motivation Tool (PEMT), was designed using learning theories, to teach children
      about asthma and its management. Sixty nine children were enrolled during an ED
      visit for acute asthma between May 2006 and November 2006. Socio-demographic and
      asthma knowledge information was gathered using questionnaires. An attitudinal
      survey was used to assess the acceptance of the program. RESULTS: Eighty one
      percent (n=56) of the children found PEMT very easy to use, and seventy five
      percent (n=52) agreed to use it in near future. There was a significant thirteen
      percent improvement in knowledge of asthma after the completion of this computer
      assisted asthma education program (p=0.01). CONCLUSION: PEMT is highly acceptable
      and is an effective way to provide asthma education in an ED setting.

PMID- 18057568
TI  - A systems theory approach to career decision making.
AB  - Many career development studies have linked career indecision, an inability to
      make a decision about the vocation one wishes to pursue, to interpersonal and
      intrapersonal processes. Systems theory can help to explain the processes behind
      these concepts in a way that other theories have not been able to explain.
      Systems Theory Framework, (STF, Patton and McMahon, 1997), incorporates both the
      contextual system, e.g., parents and peers, and the individual system (i.e.,
      STF's content component). Process, the second component, identifies the presence
      of recursive interaction processes within the individual and the context, as well
      as, between the individual and the context. STF brings back the value of
      interdependence. Specific systemic constructs are useful in career decision
      making and can add a practical dimension on to the counseling process.

PMID- 18057569
TI  - Work place issues surrounding healthcare professionals with disabilities in the
      current labor market.
AB  - Healthcare professionals, nurses with and without disabilities, administrators
      and personnel directors were surveyed to explore hiring practices and attitudes
      towards working with nurses with disabilities employed in clinical settings.
      Specifically the purpose of the study was to gather and analyze data regarding
      the perceptions of two groups towards nurses with disabilities: 1) employers and
      2) other nurses (with and without a disability). The study defined a nurse with a
      disability as an RN who has an activity limitation, specifically an altered
      activity capability which limits mobility, ambulation, strength, coordination, or
      equilibrium. Findings suggest that nurses are more likely to be willing to work
      with an RN with a disability if they had worked with one in the past. However,
      overall acceptance of RNs with disabilities was not broad.

PMID- 18057570
TI  - Gender as a differential indicator of the employment discrimination experiences
      of Americans with multiple sclerosis.
AB  - Information from the Integrated Mission System of the United States Equal
      Employment Opportunity Commission (EEOC) was used to investigate the employment
      discrimination experiences of women and men with multiple sclerosis (MS).
      Spanning the years 1992 to 2003, the EEOC database included 3,663 allegations of
      discrimination filed by 2,167 adults with MS. With respect to women and men with
      MS, the researchers examined the comparability of a) demographic characteristics;
      b) industry designations, locations, and size of employers; c) the nature of
      discrimination alleged; and d) the legal outcome or resolution of those
      allegations. On average, women and men with MS were in their early forties, with
      the majority of both groups being Caucasian. Both women and men were most likely
      to allege discrimination related to discharge and reasonable accommodations,
      although women were more likely to file harassment charges than men. Men with MS
      were more likely to allege discrimination regarding hiring and reinstatement.
      Women with MS were more likely to file allegations against employers in the
      service industries, and men were more likely to file allegations against
      employers in the construction, manufacturing, and wholesale industries. No gender
      differences were found in the geographic distribution of allegations. Both groups
      had comparable rates of merit closures (23% vs. 27%) as a result of the EEOC's
      investigatory process. Implications for rehabilitation counseling and employer
      oriented interventions are discussed.

PMID- 18057571
TI  - Workplace discrimination and cancer.
AB  - Data from the Equal Employment Opportunity Commission (EEOC) Integrated Mission
      System database were analyzed with specific reference to allegations of workplace
      discrimination filed by individuals with cancer under ADA Title One. These 6,832
      allegations, filed between July 27, 1992 and September 30, 2003, were compared to
      167,798 allegations from a general disability population on the following
      dimensions: type of workplace discrimination; demographic characteristics of the
      charging parties (CPs); the industry designation, location, and size of
      employers; and the outcome or resolution of EEOC investigations. Results showed
      allegations derived from CPs with cancer were more likely than those in the
      general disability population to include issues involving discharge, terms and
      conditions of employment, lay-off, wages, and demotion. Compared to the general
      disability group, CPs with cancer were more likely to be female, older, and
      White. Allegations derived from CPs with cancer were also more likely to be filed
      against smaller employers (15-100 workers) or those in service industries.
      Finally, the resolution of allegations by CPs with cancer were more likely to be
      meritorious than those filed from the general disability population; that is,
      actual discrimination is more likely to have occurred.

PMID- 18057572
TI  - Brain hemisphere dominance and vocational preference: a preliminary analysis.
AB  - Recent developments in split-brain theory add support to the concept of
      specialization within brain hemispheres. Holland's vocational personality theory
      may overlap with Human Information Processing (HIP) characteristics. Holland's
      six RIASEC codes were developed to identify vocational personality
      characteristics, and HIP scales were designed to measure hemispheric laterality.
      Relationships between the two scales were evaluated through canonical correlation
      with some significant results, however not all Holland scale scores correlated
      with left, right, or integrated hemispheric preference. Additional findings
      related to participants self-perception of music and math ability were also
      correlated. Findings on this added analysis revealed a high correlation between
      perception of musical ability and right brain function but not between
      mathematical concept and left brain alone. Implications regarding vocational
      choice and work are discussed.

PMID- 18057573
TI  - Problem gambling in the workplace, characteristics of employees seeking help.
AB  - Few rigorous research studies exist to define the impact problem gambling may
      have on the workforce and the workplace. This study is an initial attempt to
      address this void by exploring the vocational patterns and demographics of
      callers with self report gambling problems to a state helpline. It utilizes Chi
      squared Automatic Interaction (CHAID) Technique analysis to assess 1072 working
      age callers with gambling related problems. The goal of this exploratory
      investigation is to determine if the issue of problem gambling in the workplace
      warrants further research and, potentially, design of interventions. Discussion
      centers on the use of the information for development of employer based
      prevention and intervention efforts.

PMID- 18057574
TI  - An ecological approach to facilitate successful employment outcomes among people
      with multiple chemical sensitivity.
AB  - Many adults with multiple chemical sensitivity (MCS) must prematurely exit the
      workforce because of the severity of their MCS symptoms, the resulting disability
      stigma, and their unmet needs for on-the-job accommodations. To help individuals
      with MCS continue working or re-enter employment, rehabilitation professionals
      must understand the barriers resulting in unemployment and implement
      interventions to reduce or remove those barriers. In this article, the Ecological
      Model of Career Development is presented as a scheme for identifying barriers and
      implementing rehabilitation interventions to improve the employment outcomes
      among people with MCS.

PMID- 18057575
TI  - Situational leadership and persons with disabilities.
AB  - Does situational leadership style impact workers with disabilities? Situational
      leadership as a model and style of organizational management is defined. With a
      concentration on workers with disabilities, employer and employee perceptions of
      the workplace environment are analyzed as a contributing factor to the choice of
      leadership styles. Leadership style and its potential impact on workers with
      disabilities are included. Advantages of situational leadership style as an
      organizational model for managers that matches the intricate needs of workers
      with disabilities are argued. Methods for increasing awareness of the needs of
      persons with disabilities in the workplace and improving leadership models are
      discussed. Implications and potential outcomes for workers with disabilities
      based on the use of situational leadership by managers are discussed.

PMID- 18057576
TI  - Vaccination against mosquito borne viral infections: current status.
AB  - Mosquito borne infectious diseases are among important group of diseases
      worldwide. Vaccination is available for some tropical mosquito-borne diseases,
      especially for Japanese encephalitis virus infection and yellow fever. There are
      also several attempts to develop new vaccines for the other mosquito-borne
      diseases such as malaria, dengue infection and West Nile virus infection. In this
      article, the author reviews the issues on vaccination of some important tropical
      mosquito borne infectious diseases.

PMID- 18057577
TI  - Increased expression of TRAIL and its receptors on peripheral T-cells in type 1
      diabetic patients.
AB  - BACKGROUND: Type-I diabetes is an autoimmune inflammatory disease in which
      pancreatic beta-cells are selectively destroyed by infiltrating cells. TNF
      related apoptosis-inducing ligand (TRAIL) is a type-II membrane protein of the
      TNF superfamily which is expressed in different tissues, including pancreas and
      lymphocytes. In humans, TRAIL interacts with four membrane receptors. TRAIL-R1
      and TRAIL-R2 have cytoplasmic death domains, and can activate both caspases and
      NFkappaB pathways. The other two receptors, TRAIL-R3 and TRAIL-R4, are decoy
      receptors not capable of activating caspase cascade but may activate NF-kappaB
      and block apoptosis. As human beta cells are sensitive to TRAIL induced
      apoptosis, signaling via these molecules is considered to be a probable way of
      beta cell destruction. These molecules also are important in suppression of
      autorective T cells and immunoregulation. OBJECTIVE: To explore the importance of
      TRAIL and its receptors at pathogenesis of type-I diabetes, we compared
      expression of these molecules on T-cells of diabetic patients and healthy
      controls. METHODS: In this study, expression of TRAIL and its receptors at
      protein and mRNA levels were studied in freshly isolated peripheral T cells of 55
      type I diabetic patients and 50 healthy individuals by flowcytometry, western
      blot and RT-PCR. RESULTS: We found that expression of TRAIL and its receptors in
      peripheral T-cells at both protein and mRNA levels are significantly increased in
      patients (except for TRAIL-R2 mRNA which was slightly higher in controls) but
      increase in TRAIL, TRAIL-R3 (2.7% vs. >0.5%) and TRAIL-R4 (2.6% vs. >0.5%) is
      more considerable. sTRAIL in sera of patients was significantly lower than in
      controls (P=0.01). CONCLUSION: Our results explain resistance of autoreactive T
      cells to immunoregulatory mechanisms. Besides, increased expression of TRAIL in
      autoreactive T-cells may play an important role in beta-cell destruction. Lower
      level of sTRAIL in diabetic patients may be a reason for hyperactivation of
      autoreactive T-cells.

PMID- 18057578
TI  - Production and characterization of a monoclonal antibody against an antigen on
      the surface of non-small cell carcinoma of the lung.
AB  - BACKGROUND: Lung carcinoma is a multiple type cancer comprising of small cell and
      non-small cell carcinomas (NSCLC). For therapeutic and diagnostic purposes, serum
      monoclonal antibodies have been produced against lung cancer. OBJECTIVE: To
      characterize a murine monoclonal antibody (ME3D11) reactive with human NSCLC.
      METHODS: A murine monoclonal antibody (ME3D11) reactive with human NSCLC was
      selected after immunization of BALB/c mice with a human large cell carcinoma with
      neuroendocrine differentiation, and was tested by immunofloursence staining and
      Western blot analysis. RESULTS: Our study showed that the antigen recognized by
      ME3D11 antibody was a cell surface antigen of 170kDa. This antigen is expressed
      on the cell surface of all NSCLC and a few carcinoma cell lines. In contrast,
      this antigen is neither expressed on the cell surface of human sarcoma, nor on
      the hematopoietic and normal cell lines. This antibody had no effect on
      spontaneous proliferation of Mehr-80 cell line in vitro. CONCLUSIONS: High degree
      of binding of this monoclonal antibody to NSCLC and some other carcinoma cells
      warrants further studies on its potential use in diagnosis and therapy of cancer
      by conjugation to drugs, toxins or radionuclides.

PMID- 18057579
TI  - Aqueous humor levels of soluble Fas and Fas-ligand in patients with primary open
      angle and pseudoexfoliation glaucoma.
AB  - BACKGROUND: Glaucoma is one of the most common causes of blindness and is usually
      associated with elevated intraocular pressure. In patients with primary open
      angle glaucoma the number of trabecular meshwork cells is decreased. Death of the
      trabecular meshwork cells may be a result of apoptosis. OBJECTIVE: To investigate
      the aqueous humor levels of soluble Fas (sFas) and Fas-Ligand (sFasL) in
      glaucomatous patients. METHODS: Concentration of sFas and sFasL were measured by
      ELISA in 41 eyes with glaucoma (21 with pseudoexfoliation and 20 with primary
      open angle glaucoma) and 39 eyes with cataract as controls. RESULTS: The sFas
      concentration was lower in the primary open angle than the pseudoexfoliation
      glaucoma and the cataract groups (P=0.002 and P= 0.004, respectively). The sFasL
      level did not show any significant difference in the three groups. CONCLUSION: A
      lower level of sFas may provide proper microenvironment for increased apoptosis
      of trabecular meshwork cells in primary open angle glaucoma.

PMID- 18057580
TI  - Effect of Ganoderma lucidum on cytokine release by peritoneal macrophages.
AB  - BACKGROUND: The water-soluble extract of Ganoderma lucidum (Reishi) has been used
      as an immunomodulator to stimulate spleen cells proliferation and cytokine
      expression. OBJECTIVES: To investigate the effect of Ganoderma lucidum (G.
      lucidum) on cytokine production by mice peritoneal macrophages. METHODS: Mice
      peritoneal macrophages were prepared by intra-peritoneal injection of 5 ml cold
      PBS. Peritoneal macrophages were plated out at 1X10(6) cell/well in 1ml RPMI 1640
      medium supplemented with 10%FCS, 50 microg streptomycin and 50U penicillin. Cells
      were incubated in the presence or absence of different concentrations of G.
      lucidum at 37 degrees C and 5% CO2 for 48 hours. Cell free medium was removed and
      used for cytokine assay by ELISA method (Bender med system). RESULTS: The results
      showed no significant differences in cell viability at concentrations ranged from
      0-40 microg/ml compared with control group. G. lucidum enhanced IL-1beta, TNF
      alpha and NO production in a concentration dependent manner. However, it is not
      clear if the enhancement of NO release is due to direct effect of G. lucidum on
      NO synthesis or by indirect endogenous modulation via cytokines. IL-12 release by
      peritoneal macrophages was also increased in response to different concentrations
      of G. lucidum, but maximum enhancement was induced in response to 5 microg/ml of
      G. lucidum (P<0.001). CONCLUSION: Our results indicate that G. lucidum at
      concentrations used has a positive effect on cytokine release and NO production
      by peritoneal macrophages. Therefore, it is concluded that G. lucidum at moderate
      concentrations improves macrophage function through cytokine and NO release.

PMID- 18057581
TI  - ICAM-1 polymorphisms (G241R, K469E), in coronary artery disease and myocardial
      infarction.
AB  - BACKGROUND: Inflammation plays a critical role in atherogenesis. The initial step
      in atherosclerosis is the adhesion of leukocytes to activated endothelial cells
      mediated by ICAM-1, an inflammatory protein. Several polymorphisms for
      Intracellular adhesion molecule -1(ICAM-) gene have been described. OBJECTIVES:
      To determine the possible role of G241R and K469E polymorphisms in development of
      coronary artery disease and MI. METHODS: G241R polymorphism was investigated in
      303 patients with angiographically documented CAD, including 151 patients with
      acute or chronic myocardial infarction (MI), and a control group consisting of
      141 healthy subjects with normal coronary angiogram. K469E polymorphism was
      investigated in 309 patients with CHD, including155 patients with MI, and
      compared with 150 healthy subjects without CHD as the control group. Finally,
      G241R and K469R polymorphisms were assessed concurrently in 300 patients with CHD
      including 152 patients with MI and 140 healthy normal subjects without coronary
      heart disease (CHD). RESULTS: Although the frequency of GR and RR genotypes were
      higher in the control group compared to the CHD patients, the difference was not
      statistically significant (7.09% vs. 5.6% and 1.4% vs. 0%, P=0.27and P=0.24,
      respectively). Despite the higher frequency of KK genotype in the CHD group, the
      difference was not significant (29.1% vs. 24.6%, P=0.62). KKGG genotype was more
      frequent in the CHD group, however the difference was not significant (31.1% vs.
      27.3%, P=0.66). CONCLUSION: No strong relation was found between G241R and K469E
      polymorphisms and occurrence of CHD and MI in the studied population from Fars
      province, Iran.

PMID- 18057582
TI  - Cytokine production in Hymenolepis nana infection.
AB  - BACKGROUND: Although many experimental studies provide convincing evidence that
      type II immunity is protective against helminths, recent data in mice demonstrate
      that Th1 is also important in some cestodes like Hymenolepis nana. OBJECTIVES: To
      identify the role of Th1 and Th2 lymphocytes in immunity against H. nana, the
      levels of IL-12, IFNgamma, IL-5, and IL-13 were determined in serum of humans
      infected with this cestode. METHODS: A total of 31 patients (case) with H. nana
      infection and 30 clinically healthy individuals (control) was included in this
      study. Measurements of IL-12, IFNgamma, IL-13 and IL-5 in serum samples were
      performed by solid-phase sandwich enzyme linked immunosorbant assay. Differential
      leukocyte count was also done. T test, Mann Whitney U test and Wilcoxan W test
      were used for data analysis. RESULTS: The mean concentrations of IFNgamma, IL-12
      and IL-5 in the sera of patients with H. nana infection were higher than the
      control group, but only the differences between the concentrations of IFNgamma
      (P<0.001) and IL-13 (P<0.05) in the two groups were significant. There was an
      increase in the percentage of monocytes, eosinophils and lymphocytes in patients
      when compared to the controls, but this increase was not significant.
      CONCLUSIONS: Results from the present study in humans are in agreement with
      experimental studies in animals in which both Th1 and Th2 responses occur in H.
      nana infection.

PMID- 18057583
TI  - HLA class I gene polymorphism in Iranian patients with Papillon-Lefevre Syndrome.
AB  - BACKGROUND: Papillon-Lefevre Syndrome (PLS) is a rare autosomal recessive
      disorder characterized by diffused palmoplantar keratoderma and severe
      periodontitis. Increased susceptibility to infections due to impairment of the
      immune system is considered to be involved in pathoetiology of this disease.
      OBJECTIVES: According to the crucial function of HLA molecules in immune
      responses and association between certain HLA class I alleles and some
      periodontal or skin diseases, this study was designed to evaluate the relation of
      HLA class I genes and PLS. METHODS: HLA class I genes were typed by PCR-SSP
      (Polymerase Chain Reaction with Sequence Specific Primers) method in eight
      Iranian PLS patients and 89 healthy controls. RESULTS: The results showed no
      significant difference between the patients and controls. Moreover, identical
      haplotypes or genotypes were also observed among PLS patients and their healthy
      siblings. CONCLUSIONS: It seems that further genes are involved in genetic
      susceptibility to PLS. However the results of this study showed no significant
      association between HLA class I genes and PLS, molecular analyses of killer
      immunoglobulin-like receptors (KIRs) and MHC class I chain-related gene A and B
      (MICA/B) in PLS may clear many obscure points about the genetic factors involved
      in these diseases.

PMID- 18057584
TI  - Bi5O7Br and its structural relation to alpha-Bi5O7I.
AB  - Pentabismuth heptoxide bromide, Bi5O7Br, crystallizes in the space group Cmca.
      Its structure is compared with the closely related Ibca structure of alpha
      Bi5O7I. The change in the space group is assumedly the result of a compromise
      between the different spatial needs of Br and I and the rigidity of the
      {(3)(infinity)}[Bi, O] frameworks into which they are embedded. A detailed
      procedure for the synthesis of Bi5O7Br is given.

PMID- 18057585
TI  - Rb3Y2(BO3)3 with a noncentrosymmetric structure.
AB  - Trirubidium diyttrium triborate contains zigzag chains of corner-sharing [Y2O10]
      dimers. The chains are reinforced by one independent BO3 group and crosslinked by
      the other two types of BO3 groups to form a three-dimensional framework. Channels
      along the [100] direction accommodate the Rb+ cations.

PMID- 18057586
TI  - Monoclinic PZN-8%PT [Pb(Zn(0.3066)Nb(0.6133)Ti(0.08))O(3)] at 4 K.
AB  - The structure of the relaxor ferroelectric Pb(Zn(0.3066)Nb(0.6133)Ti(0.08))O(3)
      (lead zinc niobium titanium trioxide), known as PZN-8%PT, was determined at 4 K
      from very high resolution neutron powder diffraction data. The material is known
      for its extraordinary piezoelectric properties, which are closely linked to the
      structure. Pseudo-cubic lattice parameters have led to considerable controversy
      over the symmetry of the structure. We find the structure to be monoclinic in the
      space group Cm (No. 8), with the Zn, Nb and Ti cations sharing the octahedrally
      coordinated B site (site symmetry m, special position 2a) and Pb occupying the 12
      coordinate A site (site symmetry m, special position 2a). O atoms occupy a
      disorted octahedron around the B site (site symmetry m and special position 2a,
      and site symmetry 1 and general position 4b). Atomic coordinates have been
      determined for the first time, allowing the direction of spontaneous polarization
      to be visualized.

PMID- 18057587
TI  - Fe(II)2(PO4)(OH), a synthetic analogue of wolfeite.
AB  - This paper reports the hydrothermal synthesis and crystal structure refinement of
      diiron(II) phosphate hydroxide, Fe(II)2(PO4)(OH), obtained at 1063 K and 2.5 GPa.
      This phosphate is the synthetic analogue of the mineral wolfeite, and has a
      crystal structure topologically identical to those of minerals of the triplite
      triploidite group. The complex framework contains edge- and corner-sharing
      FeO4(OH) and FeO4(OH)2 polyhedra, linked via corner-sharing to the PO4 tetrahedra
      (average P-O distances are between 1.537 and 1.544 A). Four five-coordinated Fe
      sites are at the centers of distorted trigonal bipyramids (average Fe-O distances
      are between 2.070 and 2.105 A), whereas the coordination environments of the
      remaining Fe sites are distorted octahedra (average Fe-O distances are between
      2.146 and 2.180 A). The Fe-O distances are similar to those observed in natural
      Mg-rich wolfeite, except for two Fe-O bond distances, which are significantly
      longer in synthetic Fe(2+)2(PO4)(OH).

PMID- 18057588
TI  - Iranite, CuPb10(CrO4)6(SiO4)2(OH)2, isomorphous with hemihedrite.
AB  - This study presents the first structural report of iranite, ideally
      CuPb10(CrO4)6(SiO4)2(OH)2 [copper decalead hexachromate bis(orthosilicate)
      dihydroxide], based on single-crystal X-ray diffraction data. Iranite is
      isomorphous with hemihedrite, with substitution of Cu for Zn and OH for F. The Cu
      atom is situated at the special position with site symmetry 1. The CrO4 and SiO4
      tetrahedra and CuO4(OH)2 octahedra form layers that are parallel to (120) and are
      linked together by five symmetrically independent Pb2+ cations displaying a
      rather wide range of bond distances. The CuO4(OH)2 octahedra are corner-linked to
      two CrO4 and two SiO4 groups, while two additional CrO4 groups are isolated. The
      mean Cr-O distances for the three nonequivalent CrO4 tetrahedra are all slightly
      shorter than the corresponding distances in hemihedrite, whereas the CuO4(OH)2
      octahedron is more distorted than the ZnO4F2 octahedron in hemihedrite in terms
      of octahedral quadratic elongation.

PMID- 18057589
TI  - Luminescent properties of three structures built from 3-cyano-4-dicyanomethylene
      5-oxo-4,5-dihydro-1H-pyrrol-2-olate and cadmium.
AB  - Yellow-orange tetraaquabis(3-cyano-4-dicyanomethylene-5-oxo-4,5-dihydro-1H-pyrrol
      2-olato-kappaN(3))cadmium(II) dihydrate, [Cd(C8HN4O2)2(H2O)4] x 2 H2O, (I), and
      yellow tetraaquabis(3-cyano-4-dicyanomethylene-5-oxo-4,5-dihydro-1H-pyrrol-2
      olato-kappaN(3))cadmium(II) 1,4-dioxane solvate, [Cd(C8HN4O2)2(H2O)4] x C4H8O2,
      (II), contain centrosymmetric mononuclear Cd2+ coordination complex molecules in
      different conformations. Dark-red poly[[decaaquabis(mu(2)-3-cyano-4
      dicyanomethylene-5-oxo-4,5-dihydro-1H-pyrrol-2-olato-kappa(2)N:N')bis(mu(2)-3
      cyano-4-dicyanomethylene-1H-pyrrole-2,5-diolato-kappa(2)N:N')tricadmium]
      hemihydrate], [Cd3(C8HN4O2)2(C8N4O2)2(H2O)10] x 0.5 H2O, (III), has a polymeric
      two-dimensional structure, the building block of which includes two cadmium
      cations (one of them located on an inversion centre), and both singly and doubly
      charged anions. The cathodoluminescence spectra of the crystals are different and
      cover the wavelength range from UV to red, with emission peaks at 377 and 620 nm
      for (III), and at 583 and 580 nm for (I) and (II), respectively.

PMID- 18057590
TI  - 1,1,1,1,4,4,4,4-Octacarbonyl-2,2,3,3,5,5,6,6-octamethyl-cyclo-2,3,5,6
      tetraantimony-1,4-dichromium.
AB  - The structure of the title compound, alternatively called bis(mu
      tetramethyldistibinediyl)bis(tetracarbonylchromium), [Cr2Sb4(CH3)8(CO)8],
      consists of two Me4Sb2 bridging units between Cr(CO)4 complex fragments. The
      centre of the molecule is located on a special position of 2/m symmetry. This is
      the first characterized Sb4Cr2 heterocycle.

PMID- 18057591
TI  - In search of conformationally chiral square-planar complexes: dichloridobis(2
      methoxypyridine-kappaN)copper(II).
AB  - The title compound, [CuCl2(C6H7NO)2], was synthesized during a study of
      conformationally chiral square-planar coordination compounds. The coordination
      geometry deviates from the square-planar geometry generally adopted by copper(II)
      chloride complexes with pyridine ligands towards a tetrahedral arrangement of
      ligands. The complex is conformationally chiral but crystallizes in a
      centrosymmetric space group with both enantiomers present in the unit cell.

PMID- 18057592
TI  - Two new oximate-bridged square-planar dinuclear nickel(II) complexes.
AB  - The synthesis and characterization of two new dinuclear nickel(II) complexes,
      namely bis{mu-3-[2-(dimethylamino)ethylimino]butan-2-one oximato}dinickel(II)
      bis(perchlorate) acetonitrile solvate, [Ni2(C8H16N3O)2](ClO4)2 x CH3CN, (I), and
      bis{mu-3-[2-(dimethylamino)ethylimino]-3-phenylpropan-2-one oximato}dinickel(II)
      bis(perchlorate), [Ni2(C13H18N3O)2](ClO4)2, (II), are reported. Single-crystal X
      ray analyses of the complexes reveal that the nickel(II) ions are in square
      planar N3O environments and form six-membered (NiNO)2 metallacycles. The cation
      in (II) possesses crystallographically imposed inversion symmetry.

PMID- 18057593
TI  - (Nitrato-kappaO)bis(pyridine-2-carboxamide-kappa2N1,O)mercury(II) nitrate.
AB  - In the title compound, [Hg(NO3)(C6H6N2O)2]NO3, the Hg(II) atom is five
      coordinate. The distorted square-pyramidal mercury(II) coordination environment
      is achieved by two N,O-bidentate picolinamide ligands, with one O-monodentate
      nitrate ion in the apical position. A seven-coordinate extended coordination
      environment is completed by two additional weak Hg...O interactions, one from the
      coordinated nitrate ion and one from the other nitrate ion, to give seven
      coordination. The molecules are linked into a two-dimensional network by N-H...O
      hydrogen bonds.

PMID- 18057594
TI  - Poly[mu2-(N-hydroxypyridine-2-carboxamidine)-mu2-nitrato-silver(I)].
AB  - In the title complex, [Ag(NO3)(C6H7N3O)]n or [Ag(NO3)(pyaoxH2)] (pyaoxH2 is N
      hydroxypyridine-2-carboxamidine), the Ag+ ion is bridged by the pyaoxH2 ligands
      and nitrate anions, giving rise to a two-dimensional molecular structure. Each
      pyaoxH2 ligand coordinates to two Ag+ ions using its pyridyl and carboxamidine N
      atoms, and the OH and the NH2 groups are uncoordinated. Each nitrate anion uses
      two O atoms to coordinate to two Ag+ ions. The Ag...Ag separation via the pyaoxH2
      bridge is 2.869 (1) A, markedly shorter than that of 6.452 (1) A via the nitrate
      bridge. The two-dimensional structure is fishscale-like, and can be described as
      pyaoxH2-bridged Ag2 nodes that are further linked by nitrate anions. Hydrogen
      bonding between the amidine groups and the nitrate O atoms connects adjacent
      layers into a three-dimensional network.

PMID- 18057595
TI  - Lithium aspirinate hemihydrate.
AB  - The title compound {systematic name: catena-poly[lithium(I)-mu3-acetylsalicylato
      hemi-mu2-aqua]}, {[Li(C9H7O4)] x 0.5 H2O}n, is the hemihydrate of the lithium
      salt of aspirin. The carboxylate groups and water molecules bridge between Li
      atoms to form a one-dimensional coordination chain composed of two distinct ring
      types. The water O atom lies on a twofold axis. Hydrogen bonding between water
      donors and carbonyl acceptors further links the coordination chains to form a
      sheet structure.

PMID- 18057596
TI  - Setting ambiguity in C2/c with dibromidotetrakis(1H-pyrazole
      kappaN2)manganese(II) as an example.
AB  - trans-Dibromidotetrakis(1H-pyrazole-kappaN(3))manganese(II), [MnBr2(C3H4N2)4],
      crystallizes in the C2/c space group with the Mn atom located on a centre of
      inversion. As a result, there is just one half-molecule in the asymmetric unit.
      Geometric parameters are in the usual ranges. The Mn centre is octahedrally
      coordinated by four pyrazole residues in the equatorial plane and by two bromide
      ligands in the axial positions. The molecular conformation is stabilized by N
      H...Br hydrogen bonds. The structure of the title compound had already been
      described [Lumme & Lindell (1987). J. Coord. Chem. 15, 383-392] in a different
      setting, with the Mn atoms located on inversion centres on Wyckoff position d
      (1/4, 1/4, 1/2; 3/4, 1/4, 0; 3/4, 3/4, 1/2; 1/4, 3/4, 0). In the conventional
      setting, however, the Mn atoms are situated on Wyckoff position a (0, 0, 0; 0, 0,
      1/2; 1/2, 1/2, 0; 1/2, 1/2, 1/2). In this special case, if the c axis has the
      same length as the short diagonal of the ac plane, the transformation from one
      setting into the other yields almost indistinguishable cell parameters, and the
      possibility of confusion arises. This setting ambiguity could be the reason why
      two structures in different settings might be taken as polymorphs even though
      they can easily be transformed. As a result of this, care should always be taken
      to use the conventional setting.

PMID- 18057597
TI  - An unusual chain cadmium(II) coordination polymer: catena-poly[[(2,2'-bipyridyl
      kappa2N,N')cadmium(II)]-di-mu-chlorido-[(2,2'-bipyridyl-kappa2N,N')cadmium(II)]
      di-mu-thiocyanato-kappa2N:S;kappa2S:N].
AB  - The title complex, [CdCl(NCS)(C10H8N2)]n, represents an unusual Cd(II)
      coordination polymer constructed by two types of anionic bridges and 2,2'
      bipyridyl (bipy) terminal ligands. These two types of bridges are arranged around
      inversion centers. The distorted octahedral coordination of the Cd(II) center is
      provided by two chloride ions, one N- and one S-donor atom from two thiocyanate
      ions, and a pair of N atoms from the chelating bipy ligand. Interestingly,
      adjacent Cd(II) ions are interconnected alternately by paired chloride [Cd...Cd =
      3.916 (1) A] and thiocyanate bridges [Cd...Cd = 5.936 (1) A] to generate an
      infinite one-dimensional coordination chain. Furthermore, weak interchain C-H...S
      interactions between the bipy components and thiocyanate ions lead to the
      formation of a layered supramolecular structure.

PMID- 18057598
TI  - A one-dimensional nickel(II) coordination polymer containing 2,6-dipicolinate and
      dipyrido[3,2-a:2',3'-c]phenazine.
AB  - A new coordination polymer, catena-poly[[(dipyrido[3,2-a:2',3'-c]phenazine
      kappa(2)N,N')nickel(II)]-mu-2,6-dipicolinato-kappa(4)O(2),N,O(6):O(2')],
      [Ni(C7H3NO4)(C18H10N4)]n, exhibits a one-dimensional structure in which 2,6
      dipicolinate acts as a bridging ligand interconnecting adjacent nickel(II)
      centers to form a chain structure. The asymmetric unit contains one Ni(II)
      center, one dipyrido[3,2-a:2',3'-c]phenazine ligand and one 2,6-dipicolinate
      ligand. Each Ni(II) center is six-coordinated and surrounded by three N atoms and
      three O atoms from one dipyrido[3,2-a:2',3'-c]phenazine ligand and two different
      2,6-dipicolinate ligands, leading to a distorted octahedral geometry. Adjacent
      chains are linked by pi-pi stacking interactions and weak interactions to form a
      three-dimensional supramolecular network.

PMID- 18057599
TI  - Poly[[diaquamanganese(II)]-mu(3)-4-oxido-2-oxo-1,2-dihydropyrimidine-5
      carboxylato-kappa4O4,O5:O2:O2].
AB  - In the title compound, [Mn(C5H2N2O4)(H2O)2]n, the Mn(II) ion has a distorted
      octahedral geometry and the 4-oxido-2-oxo-1,2-dihydropyrimidine-5-carboxylate
      (Hiso(2-)) anion acts as a mu3:eta(4)-bridging ligand. Two oxo O atoms from
      different Hiso(2-) ligands bridge two Mn(II) ions, forming centrosymmetric
      dinuclear building blocks. Each dinuclear building block interacts with another
      four by the coordination of the oxide groups and carboxylate O atoms, producing a
      two-dimensional framework in the ab plane. Hydrogen bonds further extend the two
      dimensional sheets into a three-dimensional supramolecular framework.

PMID- 18057600
TI  - Two mononuclear Tc complexes: [2,2'-(3-phenylpropylimino)- and [2,2'
      (propylimino)bis(ethanethiolato)](4-methoxybenzenethiolato)oxidotechnate(V).
AB  - The molecular structures of the two mononuclear title complexes, namely (4
      methoxybenzenethiolato-kappaS)oxido[2,2'-(3-phenylpropylimino)bis(ethanethiolato)
      kappa(3)S,N,S']technetium(V), [Tc(C14H21NS2)(C7H7OS)O], (I), and (4
      methoxybenzenethiolato-kappaS)oxido[2,2'-(propylimino)bis(ethanethiolato)
      kappa(3)S,N,S']technetium(V), [Tc(C7H15NS2)(C7H7OS)O], (II), exhibit the same
      coordination environment for the central Tc atoms. The atoms are five-coordinated
      (TcNOS3) with a square-pyramidal geometry comprising a tridentate 2,2'-(3
      phenylpropylimino)bis(ethanethiolate) or 2,2'-(propylimino)bis(ethanethiolate)
      ligand, a 4-methoxybenzenethiolate ligand and an additional oxide O atom.
      Intermolecular C-H...O and C-H...S hydrogen bonds between the monomeric units
      result in two-dimensional layers with a parallel arrangement.

PMID- 18057601
TI  - A new three-dimensional neutral framework of lanthanum oxalate:
      [La2(C2O4)3(DMF)(H2O)3]n.
AB  - In the title complex, poly[triaquabis(dimethylformamide)di-mu3-oxalato-mu2
      oxalato-dilanthanum(III)], [La2(C2O4)3(C3H7NO)(H2O)3]n, both La ions are
      coordinated by nine O atoms, forming slightly distorted tricapped trigonal
      prisms. The two La ions, the terminal water O atom, and the O and N atoms of the
      dimethylformamide molecule reside on twofold rotation axes, giving the two La
      centered coordination geometries twofold or pseudo-twofold symmetries. The two
      oxalate ligands, one of which rests on a center of inversion at the mid-point of
      the C-C bond, adopt different bridging modes, connecting with the La ions to form
      two types of lanthanide oxalate chains, i.e. anionic {[La(C2O4)2(DMF)(H2O)2]n
      }(n) (DMF is dimethylformamide) and cationic zigzag {[La(C2O4)(H2O)]n+}n,
      respectively. Each zigzag cationic chain is linked to four adjacent anionic
      chains via the bridging oxalate anions, and each anionic chain connects with four
      zigzag cationic chains, constructing a three-dimensional neutral framework.

PMID- 18057602
TI  - Dichlorido[(S,R(S))-1-diphenylphosphino-2
      (ethylsulfanylmethyl)ferrocene]palladium(II).
AB  - The reaction of enantiomerically pure planar chiral ferrocene phosphine thioether
      with bis(acetonitrile)dichloridopalladium yields the title square-planar
      mononuclear palladium complex as an enantiomerically pure single diastereoisomer,
      [PdFe(C5H5)(C20H20PS)Cl2]. The planar chirality of the ligand is retained in the
      complex and fully controls the central chirality on the S atom. The absolute
      configuration, viz. S for the planar chirality and R for the S atom, is
      unequivocally determined by refinement of the Flack parameter.

PMID- 18057603
TI  - catena-Poly[[aquacopper(II)]-mu-hydroxido-mu-naphthalene-1-carboxylato
      kappa2O:O']: effect of a bulky aromatic skeleton in self-assembly.
AB  - In the title coordination polymer, [Cu(C11H7O2)(OH)(H2O)]n, the Cu(II) center is
      five-coordinated by two O atoms from two different naphthalene-1-carboxylate (L)
      ligands, one O atom from one coordinated water molecule and two O atoms from two
      hydroxide anions. L ligands and hydroxide anions jointly bridge adjacent Cu(II)
      centers to generate a one-dimensional chain along the b-axis direction. The
      results reveal that the steric bulk of the naphthalene ring system in L may play
      an important role in the formation of the title complex.

PMID- 18057604
TI  - Bis[N,N'-(2-chlorobenzylidene)ethylenediamine-kappa2N,N']copper(I)
      dichloridocuprate(I) acetonitrile solvate.
AB  - The 1:1 adduct of N,N'-bis(2-chlorobenzylidene)ethylenediamine (cb2en) with
      copper(I) chloride proves to be an ionic compound with Cu(I)-centred cations and
      anions, [Cu(C16H14Cl2N2)2][CuCl2] x CH3CN. In the cation, the Cu(I) atom has a
      flattened tetrahedral coordination geometry, with a small bite angle for the
      chelating ligands, which form a double-helical arrangement around the metal
      centre. The anion is almost linear, as expected. The packing of the cations
      involves intermolecular pi-pi interactions, which lead to columns of
      translationally related cations along the shortest unit-cell axis, with anions
      and solvent molecules in channels between them.

PMID- 18057605
TI  - Poly[[triaquazinc(II)]-mu(3)-4-nitrophthalato-kappa3O1:O2:O2'].
AB  - In the title complex, [Zn(C8H3NO6)(H2O)3]n, the two carboxylate groups of the 4
      nitrophthalate dianion ligands have monodentate and 1,3-bridging modes, and Zn
      atoms are interconnected by three O atoms from the two carboxylate groups into a
      zigzag one-dimensional chain along the b-axis direction. The Zn atom shows
      distorted octahedral coordination as it is bonded to three O atoms from
      carboxylate groups of three 4-nitrophthalate ligands and to three O atoms of
      three non-equivalent coordinated water molecules. The one-dimensional chains are
      aggregated into two-dimensional layers through inter-chain hydrogen bonding. The
      whole three-dimensional structure is further maintained and stabilized by inter
      layer hydrogen bonds.

PMID- 18057606
TI  - Diaquabis(quinoxaline-2-carboxylato-kappa2N1,O)copper(II).
AB  - In the title compound, [Cu(C9H5N2O2)2(H2O)2], the Cu(II) ion lies on an inversion
      centre and has an elongated centrosymmetric octahedral environment, equatorially
      trans-coordinated by two N,O-bidentate quinoxaline-2-carboxylate ligands and
      axially coordinated by two water O atoms. Symmetry-related molecules are linked
      by strong O-H...O hydrogen bonds, involving the uncoordinated carboxyl O atom of
      the carboxylate group and the coordinated water molecules, to form a two
      dimensional network. Weak intermolecular C-H...N interactions also stabilize the
      crystal structure.

PMID- 18057607
TI  - Two isomers of Pd2(S2NC7H4)4.
AB  - The dichloromethane solvates of the isomers tetrakis(mu-1,3-benzothiazole-2
      thiolato)-kappa(4)N:S;kappa(4)S:N-dipalladium(II)(Pd-Pd), (I), and tetrakis(mu
      1,3-benzothiazole-2-thiolato)-kappa(6)N:S;kappa(2)S:N-dipalladium(II)(Pd-Pd),
      (II), both [Pd2(C7H4NS2)4] x CH2Cl2, have been synthesized in the presence of (o
      isopropylphenyl)diphenylphosphane and (o-methylphenyl)diphenylphosphane. Both
      isomers form a lantern-type structure, where isomer (I) displays a regular and
      symmetric coordination and isomer (II) an asymmetric and distorted structure. In
      (I), sitting on an centre of inversion, two 1,3-benzothiazole-2-thiolate units
      are bonded by a Pd-N bond to one Pd atom and by a Pd-S bond to the other Pd atom,
      and the other two benzothiazolethiolate units are bonded to the same Pd atoms by,
      respectively, a Pd-S and a Pd-N bond. In (II), three benzothiazolethiolate units
      are bonded by a Pd-N bond to one Pd atom and by a Pd-S bond to the other Pd atom,
      and the fourth benzothiazolethiolate unit is bonded to the same Pd atoms by,
      respectively, a Pd-S bond and a Pd-N bond.

PMID- 18057608
TI  - 5-Aminonaphthalene-1-sulfonic acid and its manganese, nickel and cobalt salts.
AB  - 5-Ammonionaphthalene-1-sulfonate monohydrate, C10H9NO3S x H2O, contains layers of
      zwitterionic molecules with the acidic sulfonic acid H atom transferred to the
      amine N atom. Within each layer, the charged groups (NH3(+) and SO3(-)) are
      directed to the surface of the layer and are inverted on adjacent molecules. The
      naphthalene rings in a given layer are all parallel. The layers are held together
      by N-H...O and O-H...O hydrogen bonds involving the ammonium, sulfonate and water
      atoms. The Mn and Ni salts crystallize as fully aquated trihydrates, namely
      hexaaquamanagnese(II) bis(5-aminonaphthalene-1-sulfonate) trihydrate,
      [Mn(H2O)6](C10H8NO3S)2 x 3 H2O, (II), and hexaaquanickel(II) bis(5
      aminonaphthalene-1-sulfonate) trihydrate, [Ni(H2O)6](C10H8NO3S)2 x 3 H2O, (III),
      in which layers of hexaaquametal(II) complexes alternate with layers of 5
      aminonaphthalene-1-sulfonate anions. The cations reside on twofold rotation axes
      and display regular octahedral coordination. The additional water molecules are
      found in the inorganic layer between the complex cations, one on a twofold axis
      and one in a general position. The anions are packed in a herring-bone
      arrangement with the rings of neighboring rows of anions approximately 43 degrees
      out of parallel. The NH2 and SO3(-) groups line the surface of the layer, where
      they participate in numerous hydrogen bonds with the water molecules. Whereas the
      Mn and Ni salts are orthorhombic, the Co salt, hexaaquacobalt(II) bis(5
      aminonaphthalene-1-sulfonate) dihydrate, [Co(H2O)6](C10H8NO3S)2 x 2 H2O, (IV),
      crystallizes in a triclinic cell of similar dimensions, with the cations situated
      on centers of inversion. The overall packing is very similar to that of the Mn
      and Ni salts, with the main differences being the absence of the solvent water
      molecule on the special position and subtle modifications in the positioning of
      the anions within their layers. This series of salts is compared with those of
      the same metals with the 5-aminonaphthalene-2-sulfonate and 4-aminonaphthalene-1
      sulfonate isomers, allowing for similarities and differences in packing to be
      discussed on the basis of the differing substitution of the naphthalene ring and,
      in some cases, differing degrees of hydration.

PMID- 18057609
TI  - The dinuclear copper(II) complexes di-mu-chlorido-bis{[N,N'-bis(4
      chlorobenzyl)propane-1,2-diamine]chloridocopper(II)} and di-mu-chlorido-bis{[N,N'
      bis(3,4-methylenedioxybenzyl)propane-1,2-diamine]chloridocopper(II)}.
AB  - The two title dinuclear copper(II) complexes, [Cu2Cl4(C17H20Cl2N2)2], (I), and
      [Cu2Cl4(C19H22N2O4)2], (II), have similar coordination environments. In each
      complex, the asymmetric unit consists of one half-molecule and the two copper
      centres are bridged by a pair of Cl atoms, resulting in complexes with
      centrosymmetric structures containing Cu(mu-Cl)2Cu parallelogram cores; the
      Cu...Cu separations and Cu-Cl-Cu angles are 3.4285 (8) A and 83.36 (3) degrees,
      respectively, for (I), and 3.565 (2) A and 84.39 (7) degrees for (II). Each Cu
      atom is five-coordinated and the coordination geometry around the Cu atom is best
      described as a distorted square-pyramid with a tau value of 0.155 (3) for (I) and
      0.092 (7) for (II). The apical Cu-Cl bond length is 2.852 (1) A for (I) and 2.971
      (2) A for (II). The basal Cu-Cl and Cu-N average bonds lengths are 2.2673 (9) and
      2.030 (2) A, respectively, for (I), and 2.280 (2) and 2.038 (6) A for (II). The
      molecules of (I) are linked by one C-H...Cl hydrogen bond into a complex [10 1]
      sheet. The molecules of (II) are linked by one C-H...Cl and one N-H...O hydrogen
      bond into a complex [100] sheet.

PMID- 18057610
TI  - A new coordination mode of 6-methylnicotinic acid in trans-tetraaquabis(6
      methylpyridine-3-carboxylato-kappaO)cobalt(II) tetrahydrate.
AB  - The title compound, [Co(C7H6NO2)2(H2O)4] x 4 H2O, contains a Co(II) ion lying on
      a crystallographic inversion centre. The Co(II) ion is octahedrally coordinated
      by two 6-methylpyridine-3-carboxylate ligands in axial positions [Co-O = 2.0621
      (9) A] and by four water molecules in the equatorial plane [Co-O = 2.1169 (9) and
      2.1223 (11) A]. There are also four uncoordinated water molecules. The 6
      methylpyridine-3-carboxylate ligands are bound to the Co(II) ion in a monodentate
      manner through a carboxylate O atom. There is one strong intramolecular O-H...O
      hydrogen bond, and six strong intermolecular hydrogen bonds of type O-H...O and
      one of type O-H...N in the packing, resulting in a complex three-dimensional
      supramolecular structure.

PMID- 18057611
TI  - [2-(2-Pyridyl)-1H-benzimidazole-kappa2N2,N3]bis(p-toluato
      kappa2O,O')manganese(II).
AB  - In the title compound, [Mn(C8H7O2)2(C12H9N3)], the manganese(II) centre is
      surrounded by three bidentate chelating ligands, namely, one 2-(2
      pyridyl)benzimidazole ligand [Mn-N = 2.1954 (13) and 2.2595 (14) A] and two p
      toluate ligands [Mn-O = 2.1559 (13)-2.2748 (14) A]. It displays a severely
      distorted octahedral geometry, with cis angles ranging from 58.87 (4) to 106.49
      (5) degrees. Intermolecular C-H...O hydrogen bonds between the p-toluate ligands
      link the molecules into infinite chains, and every two neighbouring chains are
      further coupled by N-H...O and C-H...O hydrogen bonds between the 2-(2
      pyridyl)benzimidazole and p-toluate ligands, leading to an infinite ribbon-like
      double-chain packing mode. The complete solid-state structure can be described as
      a three-dimensional supramolecular framework, stabilized by these intermolecular
      hydrogen-bonding interactions and possible C-H...pi interactions, as well as
      stacking interactions involving the 2-(2-pyridyl)benzimidazole ligands.

PMID- 18057612
TI  - Intramolecular pi-pi stacking in diaquabis(2-hydroxybenzoato-kappaO)bis(1,10
      phenanthroline-kappa2N,N')strontium(II).
AB  - In the title compound, [Sr(C7H5O3)2(C12H8N2)2(H2O)2], the Sr(II) ion is located
      on a twofold rotation axis and assumes a distorted square-antiprism SrN4O4
      coordination geometry, formed by two phenanthroline (phen) ligands, two 2
      hydroxybenzoate anions and two water molecules. Within the mononuclear complex
      molecule, intramolecular pi-pi stacking is observed between nearly parallel
      coordinated phen ligands, while normal intermolecular pi-pi stacking occurs
      between parallel phen ligands of adjacent complex molecules. Classic O-H...O and
      weak C-H...O hydrogen bonding helps to stabilize the crystal structure.

PMID- 18057613
TI  - Three sterically hindered 6-amino-5-cyano-2-methyl-4-(1-naphthyl)-4H-pyran-3
      carboxylate derivatives.
AB  - In the title compounds, 2-methoxyethyl 6-amino-5-cyano-2-methyl-4-(1-naphthyl)-4H
      pyran-3-carboxylate, C21H20N2O4, (II), isopropyl 6-amino-5-cyano-2-methyl-4-(1
      naphthyl)-4H-pyran-3-carboxylate, C21H20N2O3, (III), and ethyl 6-amino-5-cyano-2
      methyl-4-(1-naphthyl)-4H-pyran-3-carboxylate, C20H18N2O3, (IV), the heterocyclic
      pyran ring adopts a flattened boat conformation. In (II) and (III), the carbonyl
      group and a double bond of the heterocyclic ring are mutually anti, but in (IV)
      they are mutually syn. The ester O atoms in (II) and (III) and the carbonyl O
      atom in (IV) participate in intramolecular C-H...O contacts to form six-membered
      rings. The dihedral angles between the naphthalene substituent and the closest
      four atoms of the heterocyclic ring are 73.3 (1), 71.0 (1) and 74.3 (1) degrees
      for (II)-(IV), respectively. In all three structures, only one H atom of the NH2
      group takes part in N-H...O [in (II) and (III)] or N-H...N [in (IV)]
      intermolecular hydrogen bonds, and chains [in (II) and (III)] or dimers [in (IV)]
      are formed. In (II), weak intermolecular C-H...O and C-H...N hydrogen bonds, and
      in (III) intermolecular C-H...O hydrogen bonds link the chains into ladders along
      the a axis.

PMID- 18057614
TI  - Two 9-[(E)-nitrophenylvinyl]-9H-carbazoles.
AB  - The crystal structures of 9-[(E)-(4-nitrophenyl)vinyl]-9H-carbazole and 9-[(E)-(3
      nitrophenyl)vinyl]-9H-carbazole, both C20H14N2O2, are determined mainly by van
      der Waals forces and pi-pi interactions between the carbazole and benzene
      systems. However, the packing modes are different. In the 4-nitro derivative, the
      molecules in the weakly bound stack are related by a unit-cell translation, while
      in the 3-nitro derivative there are centrosymmetric pairs of molecules joined by
      pi-pi interactions and also pairs of molecules, related by another centre of
      symmetry, connected by eight relatively short C-H...O interactions.

PMID- 18057615
TI  - Supramolecular structures of bis-thionooxalamic acid esters derived from (+/-)
      cyclohexane-1,2-diamine and (+/-)-1,2-diphenylethylenediamine.
AB  - The bis-thionooxalamic acid esters trans-(+/-)-diethyl N,N'-(cyclohexane-1,2
      diyl)bis(2-thiooxamate), C14H22N2O4S2, and (+/-)-N,N'-diethyl (1,2-diphenylethane
      1,2-diyl)bis(2-thiooxamate), C22H24N2O4S2, both consist of conformationally
      flexible molecules which adopt similar conformations with approximate C2
      rotational symmetry. The thioamide and ester parts of the thiooxamate group are
      significantly twisted along the central C-C bond, with the S=C-C=O torsion angles
      in the range 30.94 (19)-44.77 (19) degrees. The twisted s-cis conformation of the
      thionooxamide groups facilitates assembly of molecules into a one-dimensional
      polymeric structure via intermolecular three-center C=S...NH...O=C hydrogen bonds
      and C-H...O interactions formed between molecules of the opposite chirality.

PMID- 18057617
TI  - 1,3-Bis[2-(dimethylaminomethyl)phenyl]triselenide.
AB  - The title compound, C18H24N2Se3, consists of discrete molecules; owing to the
      presence of strong intramolecular N...Se interactions [N...Se = 2.671 (4) and
      2.873 (4) A], the chalcogen Se atoms of the angular Se3 chain exhibit different
      coordination geometries, i.e. the terminal Se atoms are tricoordinated and
      exhibit a T-shaped environment of the CNSe2 core [N...Se-Se = 173.73 (9) and
      172.29 (9) degrees], while the central Se atom is dicoordinated to the other two
      Se atoms, with an Se-Se-Se angle of 108.32 (2) degrees.

PMID- 18057616
TI  - A three-dimensional hydrogen-bonded framework in 2-amino-6-(N
      methylanilino)pyrimidin-4(3H)-one and a ribbon of fused hydrogen-bonded rings in
      2-amino-6-(N-methylanilino)-5-nitropyrimidin-4(3H)-one.
AB  - The molecular dimensions of both 2-amino-6-(N-methylanilino)pyrimidin-4(3H)-one,
      C11H12N4O, (I), and 2-amino-6-(N-methylanilino)-5-nitropyrimidin-4(3H)-one,
      C11H11N5O3, (II), are consistent with considerable polarization of the molecular
      electronic structures. The molecules of (I) are linked into a three-dimensional
      framework by a combination of one N-H...N hydrogen bond, two independent N-H...O
      hydrogen bonds and one C-H...pi(arene) hydrogen bond. The molecules of (II) are
      linked into ribbons containing three types of edge-fused ring by the combination
      of two independent three-centre N-H...(O)2 hydrogen bonds.

PMID- 18057618
TI  - A series of substituted (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-phenylprop-2-en-1
      ones.
AB  - In the molecular structures of a series of substituted chalcones, namely (2E)-3
      (2-fluoro-4-phenoxyphenyl)-1-phenylprop-2-en-1-one, C21H15FO2, (I), (2E)-3-(2
      fluoro-4-phenoxyphenyl)-1-(4-fluorophenyl)prop-2-en-1-one, C21H14F2O2, (II), (2E)
      1-(4-chlorophenyl)-3-(2-fluoro-4-phenoxyphenyl)prop-2-en-1-one, C21H14ClFO2,
      (III), (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-(4-methylphenyl)prop-2-en-1-one,
      C22H17FO2, (IV), and (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-(4-methoxyphenyl)prop-2
      en-1-one, C22H17FO3, (V), the configuration of the keto group with respect to the
      olefinic double bond is s-cis. The molecules pack utilizing weak C-H...O and C
      H...pi intermolecular contacts. Identical packing motifs involving C-H...O
      interactions, forming both chains and dimers, along with C-H...pi dimers and pi
      pi aromatic interactions are observed in the fluoro, chloro and methyl
      derivatives.

PMID- 18057619
TI  - The 'cyclophene' [2.2.2](1,2,4)cyclophan-9-ene.
AB  - In the title compound, C18H16, the [2.2]paracyclophane geometry is restrained to
      a considerable extent despite the introduction of the extra C=C bridge; typical
      paracyclophane features, such as the elongated C-C bridges, are still observed.
      However, the bridgehead atoms of the C=C bridge are forced into unusually close
      proximity [2.657 (3) A], which in turn causes the rings to be rotated to an
      interplanar angle of 13.7 (2) degrees. The packing involves hexagonally close
      packed layers of molecules parallel to the xy plane, corresponding to the known
      '7,11' pattern of paracyclophanes, but without significant short intermolecular
      contacts.

PMID- 18057620
TI  - Hydrogen-bonding interactions in the 4-aminobenzoic acid salt of atenolol
      monohydrate.
AB  - Atenolol {or 4-[2-hydroxy-3-(isopropylamino)propoxy]phenylacetamide} crystallizes
      with 4-aminobenzoic acid to give the salt {3-[4-(aminocarbonylmethyl)phenoxy]-2
      hydroxypropyl}isopropylammonium 4-aminobenzoate monohydrate, C14H23N2O3(+) x
      C7H6NO2(-) x H2O. In the crystal structure, the water molecule, the carboxylate
      group of 4-aminobenzoate, and the hydroxy and ether O atoms of atenolol form a
      supramolecular R3(3) (11) heterosynthon. Three other types of supramolecular
      synthons link the asymmetric unit into a two-dimensional structure.

PMID- 18057621
TI  - (E)-N'-[5-chloro-3-methoxy-2-(4
      methylphenylsulfonyloxy)benzylidene]isonicotinohydrazide acetic acid solvate:
      hydrogen-bonded network of alternating R4(4)(42), R5(5)(33) and R6(6)(40) rings.
AB  - In the title compound, C21H18ClN3O5S x C2H4O2, a combination of O-H...O, N-H...O,
      C-H...O and C-H...N hydrogen bonds links the components into a complex network
      containing alternating R4(4)(42), R5(5)(33) and R6(6)(40) rings.

PMID- 18057622
TI  - Hydrogen-bonded networks in 1-(4-methoxyphenyl)-2,2-dimethylpropan-1-ol.
AB  - The asymmetric unit of the title compound, C12H18O2, contains two independent
      molecules. They differ only slightly in conformation but form completely
      different intermolecular hydrogen-bonded arrays. One molecule exhibits disorder
      in the hydroxy group region, but this does not influence the formation of
      hydrogen bonds. The bulky tert-butyl group on one side of the carbinol C atom and
      the benzene ring on the other side promote the formation of discrete dimeric
      motifs via hydrogen-bridged hydroxy groups. Dimers are further joined by strong
      hydroxy-methoxy O-H...O bonds to form chains with dangling alcohol groups. Weaker
      intermolecular C-H...O interactions mediate the formation of a two-dimensional
      network.

PMID- 18057623
TI  - Weak C-H...N[triple-bond]C hydrogen bonds in the structures of two poly(cyano)
      substituted ring systems.
AB  - In benzene-1,2,3-tricarbonitrile, C9H3N3, the packing of the two independent
      molecules is three-dimensional and complex, involving inter alia bifurcated (C
      H)2...N systems from neighbouring CH groups. In [2.2]paracyclophane-4,5,12,13
      tetracarbonitrile, C20H12N4, the [2.2]paracyclophane systems display the usual
      distortions, namely lengthened C-C bonds and widened sp3 angles in the bridges,
      narrow angles in the six-membered rings at the bridgehead atoms, and flattened
      boat conformations of the rings. The molecules are linked by a series of C-H...N
      interactions to form layers parallel to the ab plane.

PMID- 18057624
TI  - Packing in three cyclooctitol acetates.
AB  - Three cyclooctitol derivatives, in the form of a tetraacetate, (1S*,2R*,3S*,4S*)
      2,3,4-triacetoxycyclooctan-1-ylmethyl acetate, C17H26O8, and two regioisomeric
      acetonide triacetates, (3aS*,4R*,8S*,9S*,9aS*)-8,9-diacetoxy-2,2
      dimethylcyclooctano[d][1,3]dioxan-4-ymethyl acetate and (3aS,4R,7S,9R,9aS)-7,9
      diacetoxy-2,2-dimethylcyclooctano[d][1,3]dioxan-4-ylmethyl acetate, both
      C18H28O8, have been studied. The conformation of the cyclooctane ring in the
      three compounds is quite close to the boat-chair form of the parent hydrocarbon.
      Packing is effected through weak C-H...O and van der Waals contacts.

PMID- 18057625
TI  - An unusual oligomerization/oxidation reaction of a 3-boron-substituted 1
      phenylbuta-1,3-diene produces 6,9,16,19-tetraphenyl-5,15-distyryl-3,13,25,26
      tetraoxa-2,12-diborapentacyclo[16.2.2.2(8,11).1(2,5).1(12,15)]hexacosa
      1(20),7,10,17-tetraene.
AB  - The unusual title macrocyclic structure, C60H54B2O4, has been isolated from
      exposure of 3-BF(3)-1-phenylbuta-1,3-diene to both air and moisture in an attempt
      to obtain crystals of the starting butadiene compound. Formation of the
      macrocycle from six molecules of the starting butadiene material is rationalized
      and its structural features are compared with those of other B(OR)2-substituted
      cyclohexane and benzene ring containing structures. Molecules reside on
      crystallographic centers of inversion and there are no intermolecular
      interactions of note in the crystal structure.

PMID- 18057626
TI  - Monohydrous dihydrogen phosphate salts of norfloxacin and ciprofloxacin.
AB  - Norfloxacin and ciprofloxacin crystallize with phosphoric acid in aqueous
      solution to give the salts 4-(3-carboxy-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7
      quinolyl)piperazinium dihydrogenphosphate monohydrate, C16H19FN3O3(+) x H2PO4(-)
      x H2O, and 4-(3-carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-7
      quinolyl)piperazinium dihydrogenphosphate monohydrate, C17H19FN3O3(+) x H2PO4(-)
      x H2O, respectively. In the crystal structures, the phosphate anions and the
      piperazine rings of norfloxacin or ciprofloxacin form a 12-membered
      supramolecular synthon, viz. R4(4)(12). The synthons R4(4)(12) and R2(2)(8)
      formed between adjacent phosphate anions result in the three-dimensional
      structures.

PMID- 18057627
TI  - Hydrogen-bonding patterns in enaminones: (2Z)-1-(4-bromophenyl)-2-(pyrrolidin-2
      ylidene)ethanone and its piperidin-2-ylidene and azepan-2-ylidene analogues.
AB  - The title compounds, namely (2Z)-1-(4-bromophenyl)-2-(pyrrolidin-2
      ylidene)ethanone, C12H12BrNO, (I), (2Z)-1-(4-bromophenyl)-2-(piperidin-2
      ylidene)ethanone, C13H14BrNO, (II), and (2Z)-2-(azepan-2-ylidene)-1-(4
      bromophenyl)ethanone, C14H16BrNO, (III), are characterized by bifurcated intra-
      and intermolecular hydrogen bonding between the secondary amine and carbonyl
      groups. The former establishes a six-membered hydrogen-bonded ring, while the
      latter leads to the formation of centrosymmetric dimers. Weak C-H...Br
      interactions link the individual molecules into chains that run along the [011],
      [101] and [101] directions in (I)-(III), respectively. Additional weak Br...O, C
      H...pi and C-H...O interactions further stabilize the crystal structures.

PMID- 18057628
TI  - 2'-(4-Chlorophenyl)-2,3,4,5,6,7-hexahydro-4',7'-methanospiro[9H-fluorene-9,3'-1H
      indazole]-1'-carbonitrile and methyl 4'-chloro-2'-(4-chlorophenyl)-1'
      cyanospiro[9H-fluorene-9,3'-pyrazolidine]-4'-carboxylate.
AB  - The title compounds, C27H22ClN3, (IV), and C24H17Cl2N3O2, (V), were synthesized
      as part of our ongoing studies on (2+3)-cycloaddition reactions. Compound (V)
      crystallizes with two molecules in the asymmetric unit. The pyrazolidine ring of
      compound (IV) adopts a twisted conformation, while in compound (V) it adopts a
      twisted and an envelope conformation in the two molecules. There are short
      intermolecular contacts, which can be recognized as unconventional hydrogen
      bonds, in both structures.

PMID- 18057629
TI  - (Z)-3-(Benzo[b]thiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile and (E)-3
      (benzo[b]thiophen-2-yl)-2-(3,4-dimethoxyphenyl)acrylonitrile. [corrected].
AB  - The title compounds, C20H17NO3S, (I), and C19H15NO2S, (II), were prepared by the
      reaction of benzo[b]thiophene-2-carbaldehyde with (3,4,5
      trimethoxyphenyl)acetonitrile and (3,4-dimethoxyphenyl)acetonitrile,
      respectively, in the presence of methanolic potassium hydroxide. In (I), the C=C
      bond linking the benzo[b]thiophene and the 3,4,5-trimethoxyphenyl units has E
      geometry, with dihedral angles between the plane of the bridging unit and the
      planes of the two adjacent ring systems of 5.2 (3) and 13.1 (2) degrees,
      respectively. However, in (II), the C=C bond has Z geometry, with dihedral angles
      between the plane of the bridging unit and the planes of the adjacent
      benzo[b]thiophene and 3,4-dimethoxyphenyl units of 4.84 (17) and 76.09 (7)
      degrees, respectively. There are no significant intermolecular hydrogen-bonding
      interactions in the packing of (I) and (II). The packing is essentially
      stabilized via van der Waals forces.

PMID- 18057630
TI  - Four substituted pyrazolines.
AB  - In the title compounds 5-(3-fluoro-4-phenoxyphenyl)-1,3-biphenyl-4,5-dihydro-1H
      pyrazole, C27H21FN2O, (I), 3-(4-chlorophenyl)-5-(3-fluoro-4-phenoxyphenyl)-1
      phenyl-4,5-dihydro-1H-pyrazole, C27H20ClFN2O, (II), 5-(3-fluoro-4-phenoxyphenyl)
      3-(4-methylphenyl)-1-phenyl-4,5-dihydro-1H-pyrazole, C28H23FN2O, (III), and 5-(3
      fluoro-4-phenoxyphenyl)-3-(4-methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrazole,
      C28H23FN2O2, (IV), the five-membered pyrazole ring exists in an envelope
      conformation. The crystal structure of (I) has three independent C-H...pi
      intermolecular interactions. In (II), an intermolecular C-Cl...pi contact is
      present, forming molecular chains. Replacement of this chloro group in (II) by a
      methyl group yields an isomorphic crystal structure, (III).

PMID- 18057631
TI  - A polymorph of butobarbital with two distinct hydrogen-bonding motifs.
AB  - N-H...O bonding in a form of 5-butyl-5-ethylbarbituric acid (systematic name: 5
      butyl-5-ethyl-1,3-diazinane-2,4,6-trione), C10H16N2O3, produces two distinct one
      dimensional motifs, viz. tape and ladder. Both are different from the ribbon
      chain motif observed in two previously reported polymorphs of the same compound.

PMID- 18057632
TI  - Three 9-[(E)-2-(4-halogenophenyl)vinyl]-9H-carbazoles.
AB  - The crystal structures of 9-[(E)-2-(4-fluorophenyl)vinyl]-9H-carbazole, C20H14FN,
      (I), 9-[(E)-2-(4-chlorophenyl)vinyl]-9H-carbazole, C20H14ClN, (II), and 9-[(E)-2
      (4-bromophenyl)vinyl]-9H-carbazole, C20H14BrN, (III), are determined mainly by
      van der Waals forces. The chloro and bromo derivatives are highly isomorphous,
      while the fluoro derivative has a different packing mode. Weak C-H...X
      interactions are also involved in the crystal packing. The molecular structures
      of the three compounds are similar, with relatively large twist angles of ca 55
      degrees between the carbazole and benzene planes.

PMID- 18057633
TI  - (E)-3-{2-amino-4-ethoxy-6-[N-(4-methoxyphenyl)-N-methylamino]pyrimidin-5-yl}-1
      phenylprop-2-en-1-one: a boat-shaped pyrimidine ring and a chain of hydrogen
      bonded R4(2)(8) and R2(2)(20) rings.
AB  - In the title compound, C23H24N4O3, the pyrimidine ring adopts an almost perfect
      boat conformation, and the bond distances provide evidence for some polarization
      of the molecular-electronic structure. Two independent N-H...O hydrogen bonds
      link the molecules into chains of edge-fused R2(4)(8) and R2(2)(20) rings.

PMID- 18057634
TI  - Benzyl N,N-bis[2-(pentafluoroanilino)ethyl]carbamate.
AB  - The title compound, C24H17F10N3O2, exhibits intramolecular N-H...O hydrogen
      bonding, as well as intramolecular Ar...Ar(F) face-to-face interactions. The
      molecules are linked together by N-H...F-C hydrogen bonds, forming chains
      parallel to the a axis. Adjacent symmetry-related chains are combined in double
      zipper-like ribbons by parallel Ar(F)...Ar(F) offset pi-stacking interactions.

PMID- 18057635
TI  - Solar-thermic sewage sludge treatment in extreme alpine environments.
AB  - In the framework of a program for environmental protection conducted by the
      German mountaineers' club (DAV) problems emerging from residual solids
      accumulating in on-site wastewater treatment plants of mountain refuges were
      investigated. To handle these problems in an ecologically and economically
      reasonable way two devices for solar-supported treatment of sludge and bio-solids
      have been developed. These units support gravity-filtration and evaporation of
      liquid sludge as well as thermal acceleration of composting processes. Two solar
      sludge dryers were installed and operated without external energy supply at
      alpine refuges treating primary and secondary sludge, respectively. Batch-filling
      during the season could increase load capacity and a total solids concentration
      of up to 40% could be achieved before discharge at the beginning of the next
      season. The promising results from the solar sludge dryer encouraged for the
      development of a solar composter. The period of temperature levels suitable for
      composting biosolids in mountain areas can be extended considerably by
      application of this technology--measured temperature distribution indicated no
      freezing at all.

PMID- 18057636
TI  - Modelling as a tool when interpreting biodegradation of micro pollutants in
      activated sludge systems.
AB  - The aims of the present work were to improve the biodegradation of the endocrine
      disrupting micro pollutant, bisphenol A (BPA), used as model compound in an
      activated sludge system and to underline the importance of modelling the system.
      Previous results have shown that BPA mainly is degraded under aerobic conditions.
      Therefore the aerobic phase time in the BioDenitro process of the activated
      sludge system was increased from 50% to 70%. The hypothesis was that this would
      improve the biodegradation of BPA. Both the influent and the effluent
      concentrations of BPA in the experiment dropped significantly after increasing
      the aerobic time. From simulations with a growth-based
      biological/physical/chemical process model it was concluded that although the
      simulated effluent concentration of BPA was independent of the influent
      concentration at steady-state, the observed drop in effluent concentrations
      probably was caused by either a larger specific biomass to influent BPA ratio,
      improved biodegradation related to the increased aerobic phase time, or a
      combination of the two. Thereby it was not possibly to determine if the increase
      in aerobic phase time improved the biodegradation of BPA. The work underlines the
      importance of combining experimental results with modelling when interpreting
      results from biodegradation experiments with fluctuating influent concentrations
      of micro pollutants.

PMID- 18057637
TI  - Comparison of and uncertainties in raw sewage COD measurements by laboratory
      techniques and field UV-visible spectrometry.
AB  - A comprehensive investigation of the uncertainty of different COD analysis
      methods (DIN, small tube tests (STT) and UV-visible spectrometry methods) has
      been carried out on potassium hydrogen phthalate standard solutions and raw
      sewage samples from a large wastewater treatment plant. The UV-visible method
      allows estimating COD equivalent concentration from the measured absorption
      spectra by means of site specific regression and correlation functions. CODdin
      and CODstt methods showed equivalent global results but specific calibration
      relationships are necessary when high accuracy is required. The CODstt method is
      suitable for immediate COD analysis in the field. Sub-sampling is the main source
      of uncertainty. Spectrometry is able to estimate CODeq with an uncertainty of the
      same order of magnitude as the uncertainty in CODdin.

PMID- 18057638
TI  - Escherichia coli in urban stormwater: explaining their variability.
AB  - The development of a model that predicts the levels of microorganisms in urban
      stormwater will aid in the assessment of health risks when using stormwater for
      both recreational uses and as an alternate water resource. However, the
      development of such a model requires an understanding of the dominant processes
      that influence the behaviour of microorganisms in urban systems. Using simple and
      multiple regression analyses this paper determines the dominant processes which
      affect the inter-event variability of the microbial indicator Escherichia coli
      (E. coli ) in four urbanised catchments. The results reveal that a number of
      antecedent climatic conditions, together with rainfall intensity, can
      significantly explain the inter-event variation in wet weather E. coli levels.

PMID- 18057639
TI  - Screening health risk assessment of micropullutants for indirect potable reuse
      schemes: a three-tiered approach.
AB  - Indirect potable reuse schemes are an important consideration in the sustainable
      management of scarce water resources. However, communities still hold real
      concerns about the potential health risks of micropullutants in recycled water
      entering their potable water supply. Microfiltration or ultrafiltration followed
      by reverse osmosis is currently the standard treatment technology for potable use
      of recycled water. Nevertheless, membranes are not 100% efficient in the removal
      of trace organic contaminants and the potential health risks of these
      micropullutants need to be assessed. The aim of this paper is to present a three
      tiered approach for the preliminary assessment of micropullutants in recycled
      water. A risk quotient is calculated by comparing measured concentrations against
      benchmark values. Tier 1 corresponds to regulated chemicals; the maximum
      contaminant level in drinking water is used as benchmark value. Tier 2
      corresponds to unregulated chemicals with toxicity information; slope factors or
      risk specific doses are used to calculate benchmark values. Tier 3 corresponds to
      unregulated chemicals without toxicity information. The "Threshold of
      Toxicological Concern" concept is used to calculate benchmark values. The
      characterization of chemicals of concern following reverse osmosis in a water
      reclamation plant and the application of the three-tiered approach for the
      evaluation of the potential health risks is presented.

PMID- 18057640
TI  - Stormwater overflow impacts on the sanitary quality of bathing waters.
AB  - New European Directive 2006/7/EC concerning the management of bathing water
      quality introduces the concept of 'active management of bathing water sanitary
      quality' which could lead to a temporary bathing prohibition in case of short
      term pollution. For the last three bathing seasons, Veolia has carried out in
      experimental mode this 'active management' concept at more than one hundred
      bathing sites with various characteristics. Results confirm the high level of
      microbiological pollution observed in sewer overflows during rainy periods, which
      is the main cause of bathing water quality deterioration. An on-line treatment
      solution has been successfully tested. This solution may be used in dense urban
      areas.

PMID- 18057641
TI  - Experience with the antibiotic resistance analysis and DNA fingerprinting in
      tracking faecal pollution at two lake beaches.
AB  - Posting or closing of swimming beaches because of faecal contamination is a
      widespread problem reported in many locations. In a risk-based approach to this
      problem, the risk to swimmers' health is assessed by field monitoring of
      indicator bacteria and the associated risks are managed by source controls and
      other remedial measures. In risk assessment, great advances have been made in
      recent years with the introduction of microbial source tracking (MST) techniques.
      Two such techniques, antibiotic resistance analysis and DNA fingerprinting, were
      applied in a study of causes of faecal contamination at two lake beaches in
      Toronto, Ontario. Both methods identified bird faeces as the dominant sources of
      E. coli. Coping with this type of pollution presents a major environmental
      challenge.

PMID- 18057642
TI  - Natural attenuation potential of downwelling streams for perfluorochemicals and
      other emerging contaminants.
AB  - Stream augmentation with tertiary treated municipal wastewater-i.e., recycled
      water-is increasingly considered as an ecologically beneficial way to utilize
      recycled water, especially in semi-arid regions of the American Southwest. There
      is concern that emerging contaminants, i.e. unregulated but biologically active
      organic compounds, may be present in recycled water and will impact on the
      aquatic environment and the underlying groundwater. Emerging contaminants include
      a wide variety of chemically disparate compounds, including pharmaceuticals,
      endocrine disruptors, and residues of perfluorochemical surfactants (PFCs). This
      paper presents background data on the occurrence and transport of PFC in Upper
      Silver Creek (USC) and Coyote Creek, in San Jose, California. USC feeds into
      Coyote Creek, which discharges into San Francisco Bay. Augmenting the natural
      flow of Coyote Creek with highly treated recycled water is currently being
      considered as a means to provide more freshwater to the river ecosystem. The
      reach of interest is approximately 1,000 m where USC flows on alluvial fan
      deposits. Data indicate that some PFCs are refractory.

PMID- 18057643
TI  - How uncertain is model-based prediction of copper loads in stormwater runoff?
AB  - In this paper, we conduct a systematic analysis of the uncertainty related with
      estimating the total load of pollution (copper) from a separate stormwater
      drainage system, conditioned on a specific combination of input data, a dynamic
      conceptual pollutant accumulation-washout model and measurements (runoff volumes
      and pollutant masses). We use the generalized likelihood uncertainty estimation
      (GLUE) methodology and generate posterior parameter distributions that result in
      model outputs encompassing a significant number of the highly variable
      measurements. Given the applied pollution accumulation-washout model and a total
      of 57 measurements during one month, the total predicted copper masses can be
      predicted within a range of +/-50% of the median value. The message is that this
      relatively large uncertainty should be acknowledged in connection with posting
      statements about micropollutant loads as estimated from dynamic models, even when
      calibrated with on-site concentration data.

PMID- 18057644
TI  - Particle behaviour consideration to maximize the settling capacity of rainwater
      storage tanks.
AB  - Design of a rainwater storage tank is mostly based on the mass balance of
      rainwater with respect to the tank, considering aspects such as rainfall runoff,
      water usage and overflow. So far, however, little information is available on the
      quality aspects of the stored rainwater, such as the behavior of particles, the
      effect of retention time of the water in the tank and possible influences of
      system configuration on water quality in the storage tank. In this study, we
      showed that the performance of rainwater storage tanks could be maximized by
      recognizing the importance of water quality improvement by sedimentation and the
      importance of the system configuration within the tank, as well as the efficient
      collection of runoff. The efficiency of removal of the particles was increased by
      there being a considerable distance between the inlet and the outlet in the
      rainwater storage tank. Furthermore, it is recommended that the effective water
      depth in a rainwater tank be designed to be more than 3 m and that the rainwater
      be drawn from as close to the water surface as possible by using a floating
      suction device. An operation method that increases the retention time by stopping
      rainwater supply when the turbidity of rainwater runoff is high will ensure low
      turbidity in the rainwater collected from the tank.

PMID- 18057645
TI  - Heavy metals speciation in soakaways sediment and evaluation of metal retention
      properties of surrounding soil.
AB  - Heavy metals speciation analysis was carried out on sediment samples accumulated
      within soakaways in an old stormwater infiltration facility in Tokyo, Japan and
      on a soil core sample collected near the facility. Heavy metals content in
      soakaways sediments were much elevated compared to nearby surface soil with the
      content for Zn, Pb and Cd reaching about 5 to 10 times the content in surface
      soil. Speciation results revealed that significant amount of the accumulated
      heavy metals were present in potential mobile fractions, posing threat of release
      to underlying soil with changing environmental conditions. Detail analyses of
      soil characteristics indicated significant heterogeneity with depth, especially
      between the surface soil and underlying soil at site. Decrease in potential
      adsorption sites with depth was observed in case of underlying soil. Reduced
      adsorption capacity for heavy metals was evidenced for underlying soil when
      compared with surface soil. Furthermore, less capability of the soil organic
      matter to bind heavy metals was evidenced through speciation analyses, which
      raises concern over the long-term pollution retention potential of the underlying
      soil receiving infiltrated runoff.

PMID- 18057646
TI  - Role of colloids in heavy metal transfer through a retention-infiltration basin.
AB  - Runoff waters from a main bridge near Nantes (France), surface waters and pore
      waters in the infiltration basin collecting runoff were analysed after filtration
      and ultrafiltration to investigate the role of colloids in the transfer of trace
      metals (Zn, Cu and Pb) from the road to the groundwater. The role of the basin in
      mitigation of the variations of physico-chemical parameters and chemical elements
      concentrations was confirmed. An increase of mobile colloidal phase by comparison
      with runoff and high concentrations of trace metals were observed in pore waters
      of the sediment. Up to 100% of Pb and 60% of Cu and Zn may be associated to
      compounds having a molecular weight above 5 kDaltons. Principal component
      analysis outlined the variability of the influence of the physico-chemical
      parameters on trace metals concentrations for the different waters. Speciation
      calculations pointed out the potential precipitation of Fe and Al oxyhydroxides
      in all kind of waters.

PMID- 18057647
TI  - Impact of hydrodynamics on the precipitation efficiency--application to HARDTAC
      reactor.
AB  - Precipitation of gypsum is studied in a HARDTAC (High-Aspect Ratio, Draft-Tube,
      Agitated Crystallizer) reactor, which is considered as the core crystallization
      unit of lots of wastewater treatment systems. Coupling Computational Fluid
      Dynamics (CFD) and population balance modelling to simulate precipitation can be
      a useful tool to come to a decision about upstream and downstream units. In the
      present study, we aim to validate such approach by investigating gypsum
      precipitation in a HARDTAC pilot unit and comparing experiments results with
      simulation. Measured nucleation and growth kinetics are used to feed the model. A
      comparison between experiments and simulations is presented in the case of gypsum
      precipitation with a given set of operating conditions. Good agreement is
      obtained for species concentrations, gypsum mass fraction and volumetric mean
      diameter but some discrepancies still remain between measured and simulated
      crystal size distribution.

PMID- 18057648
TI  - Restoration of a constructed stormwater wetland to improve its ecological and
      hydrological performance.
AB  - Although the vegetation within constructed stormwater wetlands plays an important
      role in the treatment processes taking place, its density and distribution
      depends on the wetland bathymetry and the imposed hydrologic regime. This paper
      describes an ecological and hydrological assessment of a constructed stormwater
      treatment wetland over a 5 year period. This assessment included the use of a
      continuous simulation hydrologic model combined with a Digital Elevation Model of
      the wetland bathymetry, plus a time series of vegetation maps. The combined
      spatial and temporal analysis indicates that both the frequency and duration of
      inundation has affected the fate of vegetation throughout the wetland.
      Restoration strategies have also been investigated to improve the survival of
      vegetation within the wetland.

PMID- 18057650
TI  - Investigation of multimodal zeta potential and size distribution in chemical pulp
      process water.
AB  - Multimodal zeta potential distribution in chemical birch pulp process water was
      studied by filtrating the water into fractions and subsequently measuring zeta
      potential, charge quantity, turbidity and organic substances. Filtrations were
      made using 12 microm, 1.6 microm, 1.2 microm, 0.45 microm and 0.1 microm
      membranes. The number of populations with different zeta potentials diminished
      with filtration. With the unfiltrated water, 12 microm and 1.6 microm filtrates,
      three or four different zeta potentials were observed. When the filtration was
      performed with a 1.2 microm membrane or smaller, only two populations of
      different zeta potentials were detected. The charge quantity steadily approached
      zero from unfiltrated water towards a 1.6 microm fraction filtrate. After that,
      it remained constant. Turbidity constantly decreased when using smaller
      membranes. The amount of wood extractives decreased to half with 0.1 microm
      filtration. No significant difference in the amount of carbohydrates and lignin
      between the filtrated fractions and the unfiltrated water was detected. A
      comparison dealing with particle size analysis between two different apparatuses
      was also made.

PMID- 18057649
TI  - Bromide removal by hydrotalcite-like compounds in a continuous system.
AB  - Bromide ion removal from a real water matrix by hydrortalcite-like compounds
      (HTCs) was attempted in a column reactor to control the formation of brominated
      disinfection by-products in drinking water treatment process. The performance of
      HTCs was found to be comparable to a commercially available ion exchange resin
      for relatively low alkalinity water. Also, it was deduced that HTCs are better
      than ion exchange resins for high sulfate water because of their unique ion
      selectivity. In addition, the ion exchange reactions by HTCs were faster than a
      commercially available resin. Thus, HTCs are expected to provide similar
      performance to organic resins without the concern about secondary contamination
      (i.e., elution of organic compounds from resins).

PMID- 18057651
TI  - Rapid sonic characterisation of sewer change and obstructions.
AB  - This paper reports on the development of a low-cost, rapidly deployable sensor
      for surveying live sewers for blockages and structural failures. The anticipated
      cost is an order of magnitude lower than current techniques. The technology is
      based on acoustic normal model decomposition, The instrument emits short coded
      acoustic signals which are reflected from any sewer wall defect. The acoustic
      signals can be short Gaussian pulses or longer sinusoidal sweeps and pseudo
      random noise. The processing algorithms used on the reflected signal can predict
      the extent and geometry of the pipe deformation, and the locations and
      approximate size of common blockages. The effect of the water level on the
      frequency of the fundamental mode has also been investigated. It is shown that
      the technique can be adapted to work reliably in relatively large 600 mm diameter
      sewer pipes.

PMID- 18057652
TI  - A new design of flocculation tank: the Turbomix applied to weighted flocculation.
AB  - As far as flocculation is concerned, the agglomeration of suspended particles
      into flocs is highly linked to the hydraulic behaviour of the agitation. The
      Turbomix is a special design of mixing tank; its design was developed to better
      control the flow during the flocculation stage. It enables a significant decrease
      in footprint of the process. The combination of the Turbomix and ballasted
      flocculation has been studied during pilot trials in terms of treatment
      efficiency. Its controlled hydraulic behaviour explains the efficiency of the
      process as proved by CFD investigation.

PMID- 18057653
TI  - Occurrence of perfluoroalkyl sulfonates and carboxylates in German drinking water
      sources compared to other countries.
AB  - Different homologues of C4 to C8 perfluoroalkyl carboxylates (PFCAs) and
      perfluoroalkyl sulfonates (PFASs) were detected in German surface waters, bank
      filtrates, artificially recharged groundwaters, and drinking waters. If no point
      sources are located nearby, the typically measured levels are in the low ng/L
      range. In the presence of point sources, such as a fluorochemical production
      site, a leaching agricultural fertilizer contaminated with PFCAs and PFASs, or
      drained PFC containing fire-fighting foams, much higher concentrations in the
      microg/L range occur. This situation is similar in Germany and other countries.

PMID- 18057654
TI  - Ozonation and reductive deiodination of iopromide to reduce the environmental
      burden of iodinated X-ray contrast media.
AB  - The potential of ozonation for the removal of iodinated X-ray contrast media
      (ICM) with focus on the oxidation products was examined. Iopromide used as model
      compound was dissolved in tap water, respectively in the effluent of a membrane
      bioreactor and was ozonated. Ozone (10 mg/L) was continuously introduced into a
      semi-batch reactor (35 L/h). After 30 minutes the ozone concentration was
      increased to 30 mg/L. In all experiments the iopromide concentration decreased
      very fast, whereas the decrease of the amount of organic bound iodine (AOI) was
      much lower. The concentration of iodate, the inorganic oxidation product
      increases with time, depending on the AOI decrease. The data clearly show that
      the ozonation of iopromide using a common applied ozone dosage leads to the
      formation of numerous iodinated transformation products, which are detectable by
      LC-ESI-MS. As an alternative treatment, especially for the treatment of urine or
      hospital waste water, the source for the contamination, it was tested if
      iopromide can be deiodinated by zero-valent iron. First experiments done in
      stirred batch reactors using iopromide dissolved in ultra pure water and urine
      with an initial pH of 2 showed that iopromide can be deiodinated completely by
      zero-valent iron. Even in contaminated urine collected in a hospital a
      deiodination of ICM was possible. Kinetic studies at constant pH showed that the
      deiodination can be described by pseudo-first order for equal iopromide and iron
      concentrations. The observed rate constant kobs increased with decreasing pH with
      a maximum at pH 3 with 4.76x10(-4) s(-1). The concentration of iopromide can be
      decreased by ozonation and by the reductive dehalogenation. In case of ozonation
      iodinated organic compounds are the main reaction products, whereas the reductive
      dehalogenation leads to transformation products which are not iodinated and are
      thus most probable biodegradable.

PMID- 18057655
TI  - [Parathyroid and bone. Skeletal derangement in patients with primary
      hyperparathyroidism].
AB  - One of the principle purposes in treatment of patients with primary
      hyperparathyroidism in Japan is to improve bone fragility by increasing bone
      mineral density. Persistent excess actions of parathyroid hormone could cause
      decrease in bone mineral density and bone fragility. Parathyroid surgery should
      be considered when bone mineral density in patients with the disease is in a
      range of osteoporosis. After surgery, bone mineral density is increased with time
      during several years. It is suggested relative risk of fracture decreases with
      parathyroid surgery. Recently, accumulating evidence indicates that treatment
      with oral bisphosphonates increases bone mineral density in patients with mild
      primary hyperparathyroidism, although it is yet uncertain whether it also
      prevents fracture.

PMID- 18057656
TI  - [Parathyroid and bone. Role of parathyroid hormone in the treatment of
      osteoporosis].
AB  - Parathyroid hormone (PTH) , a potent anabolic agent, produces larger increments
      in bone mass than those seen with antiresorptive agents. No further benefit is
      expected in PTH and antiresorptive combinations in treatment-naive patients of
      osteoporosis, but in cases achieving the plateau level of BMD with established
      alendronate PTH can stimulate bone formation and increase BMD again. Alendronate
      treatment after PTH therapy can maintain gains in BMD at lumbar spine and hip as
      well. Many possibilities are expected in the role of PTH therapy in osteoporosis
      treatment.

PMID- 18057657
TI  - [Parathyroid and bone. Management of parathyroid function and evaluation of bone
      metabolism in hemodialysis patients].
AB  - Disturbances in mineral and bone metabolism due to loss of kidney function
      greatly influence morbidity and quality of life, so Kidney Disease: Improving
      Global Outcomes (KDIGO) proposed the concept of chronic kidney disease-mineral
      and bone disorder (CKD-MBD). Japanese Society for Dialysis Therapy has created
      guidelines for the management of secondary hyperparathyroidism associated
      prognosis in hemodialysis patients, and we are managing parathyroid function of
      hemodialysis patients under this guideline. Bone biopsy is not recommended as
      part of routine evaluation for CKD-MBD because bone biopsy is the invasive
      examination. KDIGO proposed new histological classification of renal
      osteodystrophy, TMV classification, for standardizing a result of bone
      histomorphometry. We expect that new guideline improve the prognosis of
      hemodialysis patients.

PMID- 18057658
TI  - [Parathyroid and bone. Effects of parathyroid hormone on bone resorption and
      formation: differences between intermittent and continuous treatment].
AB  - The continuous treatment with parathyroid hormone (PTH) or endogenous PTH excess
      by primary hyperparathyroidism cause enhanced bone resorption and subsequent
      decreased bone volume. However, the intermittent treatment with PTH is expected
      as a drug for osteoporosis for its stimulation of bone formation and marked
      increase in bone volume. The mechanism of different PTH actions due to the
      administration method still remains unclear. Several reports suggested the
      hypothesis about the role of insulin-like growth factor-1, anti-apoptotic effects
      through Runx2 or Smad3 and the differences of its effects on bone resorption. The
      investigation about the mechanism of bone formation by PTH intermittent treatment
      would lead to the development of bone-forming reagent in the future.

PMID- 18057659
TI  - [Parathyroid and bone. The mechanism of anabolic function of parathyroid hormone
      on bone].
AB  - Parathyroid hormone (PTH) has been applied to postmenopausal women and several
      studies revealed that intermittent PTH treatment significantly increases lumbar
      bone mineral density and reduces fracture risk. However, the mechanism of PTH
      anabolic function on bone is not fully understood yet. PTH receptors (PPR) are
      expressed in osteoblasts and PPR stimulates multiple intracellular signal
      pathways, including those mediated by cAMP-PKA signaling pathway and PLC-PKC
      signaling pathway. Several studies demonstrate that the PKA signaling through G
      proteins in osteoblasts play important roles in regulating gene expression and
      osteogenesis by PTH.

PMID- 18057660
TI  - [Parathyroid and bone. Bone metabolism in hypoparathyroidism].
AB  - Hypoparathyoidism is classified into two categories: PTH deficient and PTH
      refractory (i.e. pseudohypoparathyrodism [PHP]). Bone metabolism is different
      between the two. In PTH deficient hypoparathyroidism such as post-operative
      hypoparathyroidism, BMD is increased with relatively low bone turnover markers.
      In PHP, which characterized by PTH resistance in proximal renal tubules, bone
      response to PTH is sometimes preserved. In some PHP cases, high bone turnover
      state is observed, which correlates with serum PTH levels.

PMID- 18057661
TI  - [Parathyroid and bone. Effect of parathyroid hormone on bone quality].
AB  - Intermittent administration of parathyroid hormone (PTH) stimulates bone
      formation, and continuous infusion of PTH stimulates bone resorption. The
      preclinical and clinical studies showed that PTH improved bone structure such as
      trabecular connectivity and cortical thickness, as well as increased bone mass.
      Its contribution to bone strength is produced by the different mechanism from the
      anti-resorptive agent. Assessment of bone geometry and site-specific bone change
      using CT will be required to evaluate its efficacy of anabolic agent on bone
      quality.

PMID- 18057662
TI  - [Parathyroid and bone. Calcimimetics and bone metabolism].
AB  - Calcimimetics suppress parathyroid hormone (PTH) secretion by allosterically
      acting on parathyroid calcium-sensing receptor. It has been already shown that
      one of calcimimetics decreases PTH level, calcium-phosphate product and bone
      specific alkaline phosphatase (BAP) in patients with secondary
      hyperparathyroidism (SHPT) caused by end-stage renal disease. It has been also
      described that this drug ameliorates osteitis fibrosa in uremic rats. However,
      there has been so far insufficient evidence showing that calcimimetics increase
      bone mineral density and decrease fractures in human. Effects of calcimimetics on
      bone metabolism need to be investigated by clinical studies for longer usage of
      this drug in the future.

PMID- 18057663
TI  - [Parathyroid and bone. Mineral and bone disorder and parathyroid function in
      chronic kidney disease].
AB  - In chronic kidney disease (CKD), mineral and hormonal abnormality is observed at
      an early stage, followed by bone disorder and vascular calcification,
      consequently leading to decreased survival. Thus, an idea of systemic disorder,
      CKD-mineral and bone disorder (CKD-MBD) has been currently advocated, and its
      management has been discussed aiming at longevity. Low serum vitamin D level,
      accumulation of phosphorus and uremic toxins, increased oxidative stress, and
      secondary hyperparathyroidism play central roles in the pathogenesis of CKD-MBD.
      Recent findings suggest that active management for CKD-MBD could improve
      mortality as well as kidney prognosis.

PMID- 18057664
TI  - [Parathyroid and bone. Secondary hyperparathyroidism after renal
      transplantation].
AB  - Serum parathyroid hormone concentrations decrease progressively during the first
      3 to 6 month after successful renal transplantation. However 1 year after
      transplantation, persistent hyperparathyroidism is common. Hypercalcemia due to
      persistent hyperparathyroidism cause graft dysfunction and cardiovascular
      calcification. Renal transplant recipients with persistent hyperparathyroidism
      need treatment with vitamin D and calcium, in some cases parathyroidectomy has to
      be considered.

PMID- 18057665
TI  - [Parathyroid and bone. Evidence and perspective of parathyroid therapy for
      patients with osteoporosis].
AB  - Parathyroid hormone (PTH) is a new management option for patients with
      osteoporosis. As an anabolic agent that affects bone remodeling and modeling, a
      novel approach to reducing fracture risk could be considered for patients with
      severe conditions. A number of trials have shown that increases in spine and hip
      bone mineral density (BMD), and reduction of fracture risk in postmenopausal
      women. Although the combination of PTH and alendronate does not seem to be
      additive, PTH followed by alendronate would yield maximum increase in BMD.
      Treatment with PTH can change the course of osteoporosis by directly stimulating
      formation of new bone, and its application should be explored in daily clinical
      practice.

PMID- 18057666
TI  - [Parathyroid and bone. Indication for parathyroidectomy in primary
      hyperparathyroidisms].
AB  - Primary hyperparathyroidism is a disease in which somatic chromosomal defects
      such as activations of oncogenes or inactivations of tumor suppressor genes
      enhance chromosomal parathyroid cell growth. Decreased calcium-sensing receptor
      causes oversecretion of PTH from abnormal parathyroid cells. Oversecreted PTH
      enhances bone turnover and finally exhibits bone fragility. In this review, the
      indications of parathyroidectomy and the effects of parathyroidectomy on bone in
      primary hyperparathyroidism are discussed.

PMID- 18057668
TI  - [Secondary osteoporosis. Bisphosphonates as a possible strategy for the
      prevention of bone destruction in rheumatoid arthritis].
AB  - Recent studies demonstrated that osteoclastic bone resorption played an important
      role in joint destruction by rheumatoid synovium. Bisphosphnates inhibit
      osteoclastic bone resorption and have been widely used for the treatment of
      osteoporosis. Bisphosphonates, such as zolendronic acid (ZA) inhibited bone
      destruction in animal models of inflammatory arthritis, although the drug was not
      effective for the suppression of inflammation. In early RA patients, ZA was
      effective to prevent bone destruction in combination with methotrexate. Targeting
      osteoclasts with bisphosphonates is an effective strategy to maintain joint
      integrity when combined with anti-rheumatic therapy.

PMID- 18057667
TI  - [Parathyroid and bone. Medical management of primary hyperparathyroidism].
AB  - Although the role of medical management for primary hyperparathyroidism (PHPT) is
      still controversial, there are subsets of symptomatic patients with PHPT who may
      benefit from medical rather than surgical treatments. Estrogen remains an
      excellent option for selected postmenopausal women. Bisphophonates may be useful
      to provide skeletal protection and to treat osteoporosis associated with PHPT.

PMID- 18057669
TI  - [Bone disease with Pain. Stress fracture].
AB  - The repetitive mechanical stress that can not break the bone in one time, may
      cause stress fractures as a consequence of the overuse syndrome. As a sport
      injury, stress fracture is reported in several parts of the body, mainly lower
      extremities, and the diagnosis is relatively easy. The physical examination shows
      tenderness and pain while moving. The evaluation of surrounding structures of the
      stress fracture is mandatory. Risk factors include female, elderly and
      individuals with low physical abilities. The proper plan of training for each
      athlete is important not only to improve performance but also to prevent stress
      fractures.

PMID- 18057670
TI  - Comparison of changes in posterior tibialis muscle length between subjects with
      posterior tibial tendon dysfunction and healthy controls during walking.
AB  - STUDY DESIGN: Case control study. OBJECTIVE: To compare posterior tibialis (PT)
      length between subjects with stage II posterior tibial tendon dysfunction (PTTD)
      and healthy controls during the stance phase of gait. BACKGROUND: The abnormal
      kinematics demonstrated by subjects with stage II PTTD are presumed to be
      associated with a lengthened PT musculotendon, but this relationship has not been
      fully explored. METHODS: Seventeen subjects with stage II PTTD and 10 healthy
      controls volunteered for this study. Subject-specific foot kinematics were
      collected using 3-D motion analysis techniques for input into a general model of
      PT musculotendon length (PTLength). The kinematic inputs included hindfoot
      eversion/inversion (HF Ev/lnv), forefoot abduction/adduction (FF Ab/Add),
      forefoot plantar flexion/dorsiflexion (FF Pf/Df), and ankle plantar
      flexion/dorsiflexion (Ankle Pf/Df). To estimate the change in PTLength from
      neutral the following model was used: PTLength = 0.401(HF Ev/lnv) + 0,270(FF
      Ab/Add) + 0.137(FF Pf/Df) + 0.057(Ankle Pf/Df). Positive values indicated
      lengthening from the subtalar neutral (STN) position, while negative values
      indicated shortening relative to the STN position. A 2-way analysis of variance
      (ANOVA) model was used to compare PTLength between groups across the stance
      phases of walking (loading response, midstance, terminal stance, and preswing).
      Also, a 2-way ANOVA was used to assess the foot kinematics that contributed to
      alterations in PTLength. The Short Musculoskeletal Functional Assessment Index
      and Mobility subscale were used to compare function and mobility. RESULTS:
      PTLength was significantly greater (lengthened) relative to the STN position in
      the PTTD group compared to the control group across all phases of stance, with
      the greatest between-group difference in PTLength occurring during preswing. The
      greater PTLength in subjects with PTTD compared to controls was principally
      attributed to significantly greater HF Ev/lnv during loading response (P = .014)
      and midstance (P = .015). During terminal stance and preswing, each kinematic
      input to estimate PTLength contributed to lengthening (main effect, P = .03 and P
      = .01, respectively). Subjects with PTTD with abnormally greater PTLength
      reported significantly lower function (P = .04) and mobility (P = .03) compared
      to subjects with PTTD with normal PTLength during walking. CONCLUSIONS: The
      greater PTLength, as determined from foot kinematics, suggests that the PT
      musculotendon is lengthened in subjects with stage II PTTD, compared to healthy
      controls. The amount of lengthening is not dependent on the phase of gait;
      however, different foot kinematics contribute to PTLength across the stance
      phase. Targeting these foot kinematics may limit lengthening of the PT
      musculotendon. Subjects with excessive PT lengthening experience a decrease in
      function.

PMID- 18057671
TI  - The effects of scapular taping on the surface electromyographic signal amplitude
      of shoulder girdle muscles during upper extremity elevation in individuals with
      suspected shoulder impingement syndrome.
AB  - STUDY DESIGN: Multifactorial, repeated-measures, within-subjects design.
      OBJECTIVES: To investigate the immediate effects of scapular taping on surface
      electromyographic (EMG) signal amplitude of shoulder girdle muscles during upper
      extremity elevation in individuals with suspected shoulder impingement syndrome.
      BACKGROUND: Individuals with shoulder impingement syndrome may present with
      increased activity of the upper trapezius and inhibition of other shoulder
      muscles active during upper extremity elevation. Scapular taping is theorized to
      normalize shoulder girdle function during scapular upward rotation by decreasing
      upper trapezius activity and increasing the activity of the lower trapezius and
      other muscles. assessed for each muscle. RESULTS: Upper trapezius activity was
      significantly lower with tape during shelf task elevation (P = .002), especially
      above 90 degrees (P<.002). Lower trapezius activity was significantly higher with
      tape (P = .043). No significant differences were found between the tape and no
      tape for other muscles for the shelf task. During shoulder abduction in the
      scapular plane, the main effect for upper trapezius showed a significant decrease
      of EMG signal amplitude (P = .047) for tape versus no tape, but no significant
      interactions were found among components of this activity, or for other muscles.
      CONCLUSION: Scapular taping decreased upper trapezius and increased lower
      trapezius activity in people with suspected shoulder impingement during a
      functional overhead-reaching task, and decreased upper trapezius activity during
      shoulder abduction in the scapular plane. Taping did not affect the other muscles
      under the loads tested, but it is possible that the activity of these muscles was
      not deficient at the time of testing.

PMID- 18057672
TI  - Body mass, nonspecific low back pain, and anatomical changes in the lumbar spine
      in judo athletes.
AB  - STUDY DESIGN: Cross-sectional study of a specific population. OBJECTIVES: To
      investigate the prevalence and coprevalence of nonspecific low back pain (nsLBP)
      and lumbar radiological abnormalities (LRA) in judo athletes. BACKGROUND: nsLBP
      and LRA occur frequently in judo athletes. High body mass has been reported to be
      associated with both nsLBP and LRA. METHODS AND MEASURES: The subjects comprised
      82 male judo athletes (mean +/- SD age, 20.1 +/- 0.9 years) from 3 weight
      categories: lightweight (n = 29), middleweight (n= 31), and heavyweight (n = 22).
      The presence of nsLBP was evaluated using a questionnaire. LRA were examined
      using plain-film radiographs and magnetic resonance imaging. The prevalence of
      nsLBP and LRA were compared among weight categories. RESULTS: The prevalence of
      nsLBP in the lightweight, middleweight, and heavyweight categories was 34.5%,
      32.3%, and 40.9%, respectively. For LRA, prevalence for the 3 weight categories
      was 65.5%, 90.3%, and 90.9%, respectively (middle-weight and heavyweight greater
      prevalence than lightweight [P<.05]). The prevalence of LRA in athletes with
      nsLBP in each category was 50.0%, 100%, and 88.9%, respectively (middleweight
      greater prevalence than lightweight [P<.05]). The prevalence of LRA in athletes
      without nsLBP in each category was 73.7%, 85.7%, and 92.3%, respectively.
      CONCLUSIONS: The prevalence of LRA was approximately 90% in the middleweight and
      heavyweight categories, which was greater than for the lightweight category.
      There was a large coprevalence of nsLBP and LRA. However, many judo athletes
      without nsLBP had LRA. The presence of LRA may not have a direct association with
      nsLBP.

PMID- 18057673
TI  - Exercise-related leg pain in collegiate cross-country athletes: extrinsic and
      intrinsic risk factors.
AB  - STUDY DESIGN: Prospective cohort design. OBJECTIVES: To determine in a sample of
      collegiate cross-country athletes (1) the percentage of athletes with history of
      exercise-related leg pain (ERLP) associated with running, (2) the incidence of
      ERLP during 1 season, (3) if factors including years of collegiate running,
      training distance, and gender are associated with ERLP, and (4) if there is a
      relationship between foot type and ERLP. BACKGROUND: ERLP is a common overuse
      pain syndrome, but little evidence exists regarding the prevalence, incidence,
      and risk factors. METHODS AND MEASURES: Eighty-eight collegiate cross-country
      athletes (44 male, 44 female) from 5 Midwest universities consented to
      participate, Prior to the season, athletes completed a questionnaire and 3
      measures of foot type were performed: navicular drop, medial longitudinal arch
      angle, and visual assessment of foot type. Athletes completed a postseason
      questionnaire regarding the season incidence of ERLP Statistical analyses of
      differences (t test, proportion test) and relationships (chi-square, relative
      risk) were conducted. RESULTS: Prior to the season, 60 of the 88 athletes (68%)
      reported a history of ERLP with bilateral medial leg pain the most common ERLP
      presentation. Over 50% of the athletes with a history of ERLP reported that the
      pain had interfered with cross-country participation. Of the 67 postseason
      respondents, 38.8% reported ERLP incidence during the season. Most athletes
      (80.8%) who reported season incidence of ERLP had a previous history of ERLP
      There were no differences between athletes with and without a history of ERLP or
      season incidence of ERLP regarding years of collegiate running, training
      distance, gender, and foot measures. CONCLUSION: ERLP history and season
      incidence was common among these cross-country athletes. The only risk factor
      identified for season incidence of ERLP was a history of ERLP.

PMID- 18057674
TI  - Regional interdependence: a musculoskeletal examination model whose time has
      come.

PMID- 18057675
TI  - Observed outcomes associated with a quota-based exercise approach on measures of
      kinesiophobia in patients with chronic low back pain.
AB  - STUDY DESIGN: Prospective series of consecutive cases. OBJECTIVES: To observe if
      kinesiophobia was altered through an education- and quota-based exercise physical
      therapy program, and to observe the relationship of kinesiophobia with other
      measures related to chronic low back pain. BACKGROUND: The role of kinesiophobia
      in worsening the chronic low back pain predicament has been documented in
      numerous studies. However, less is known of the effect of an exerciseonly-based
      physical therapy program's ability to alter kinesiophobia and improve functional
      abilities in patients with chronic low back pain. METHODS: Eighty-two patients
      with at least 3 months of low back pain, and a moderate level of disability
      (Oswestry score greater than or equal to 20) were willing to participate in this
      study. Sixty-eight of these patients completed treatment. For 68 compliant
      patients, females comprised 56%, the mean age was 43 years, the mean duration of
      symptoms was 28 months, and the primary anatomic diagnosis was disc degeneration
      (70%). Patients underwent a course of non-pain-contingent, quota-based physical
      therapy to address impairments in flexibility, strength, and lifting capacity.
      These were quantified prior to and following treatment using validated methods.
      Before and after treatment, patients completed the Fear-Avoidance Beliefs
      Questionnaire (FABQ), Tampa Scale of Kinesiophobia (TSK) Questionnaire, Oswestry
      Disability Index (ODI) Questionnaire, and a 0-to-10 visual analog scale for back
      and lower extremity pain. A 12-month follow-up was conducted using mailed
      questionnaires. RESULTS: The mean number of physical therapy visits was 14.
      Clinically and statistically significant (P<.001) improvement in flexibility,
      strength, and lifting ability were observed. Statistically significant (P<.001)
      improvement in back pain, disability, and measures of kinesiophobia were also
      noted at discharge and maintained at 12-month follow-up. At discharge, Oswestry
      scores correlated with TSK (r = .59, P<.001), FABQ-Activities (r = .55, P<.001),
      and FABQ-Work (r = .50, P<.001) scores. CONCLUSION: In this study we observed
      that kinesiophobia decreased during an intensive physical therapy program in
      which exercises were performed in a quota-based manner. Following the successful
      performance of non-pain-contingent, quota-based exercise, patients' fears of
      injury lessened, and this may have had a positive influence on disability.

PMID- 18057677
TI  - Newly developed WHO growth standards: implications for demographic surveys and
      child health programs.
AB  - OBJECTIVE: To compare estimates of undernutrition based on the World Health
      Organization (WHO) Child Growth Standards ('WHO standards') and the National
      Center for Health Statistics NCHS/ WHO international growth reference ('NCHS
      reference') and discuss implications for child health programs and reporting of
      prevalence of underweight in demographic surveys. METHODS: A cross-sectional
      study was carried out in 20 Anganwadi centers under Primary Health Centre, Anji.
      Total of 1491 under-six year children attending the Anganwadi centers were
      studied for nutritional status. Nutritional status was analyzed by NCHS standards
      by using EPI_INFO 6.04 software package and also by newly introduced WHO Child
      Growth Standards by Anthro 2005 software package. Chi-square test was used to
      compare the results. RESULTS: According to WHO standards, the prevalence of
      underweight and severe underweight for children 0-6 year was 47.4% and 16.9%
      respectively. By NCHS reference, the overall prevalence of underweight and severe
      underweight for children 0-6 years was 53% and 15% respectively. The prevalence
      of underweight as assessed by WHO standards was significantly lower when compared
      with the assessment based on NCHS reference (p< 0.01). But, WHO standards gave
      higher prevalence of severe underweight than NCHS reference though the difference
      was not statistically significant (p>0.05). CONCLUSION: In the light of newly
      developed WHO Child growth standards, all the nutrition-related indicators in
      demographic surveys like NFHS should now be derived using the WHO standards.
      There is need to reanalyze NFHS - I and NFHS - II data using WHO standards and
      findings should be made available so that it becomes comparable and trends over
      the years can be studied.

PMID- 18057678
TI  - Growth hormone in intra-uterine growth retarded newborns.
AB  - OBJECTIVE: To study growth hormone levels in IUGR and healthy controls and its
      association with birth weight and ponderal index. METHODS: We studied 50 Intra
      uterine growth retarded (IUGR) and 50 healthy newborns born at term by vaginal
      delivery in JIPMER, Pondicherry, India. Cord blood was collected at the time of
      delivery for measurement of growth hormone. RESULTS: When compared with healthy
      newborns, IUGR newborns had higher growth hormone levels (mean +/- SD, 23.5 +/-
      15.6 vs 16.2 +/- 7.61 ngm/ml, P = 0.019). A negative correlation was identified
      between growth hormone levels and birth weight (r2 = - 0.22, P = 0.03) and
      ponderal index (r2 = - 0.36, P = 0.008). Correlation of growth hormone levels was
      much more confident with ponderal index than with birth weight. CONCLUSION: At
      birth IUGR infants display increased growth hormone levels which correlate with
      ponderal index much more confidently than with birth weight.

PMID- 18057679
TI  - Spectrum of severe skeletal dysplasias in North India.
AB  - OBJECTIVE: Severe skeletal dysplasias are a group of bone growth disorders
      characterized by a lethal outcome in utero or infancy. We describe our experience
      of the severe skeletal dysplasias diagnosed amongst fetal autopsies done at a
      tertiary level centre over a five year period. METHODS: We evaluated 15 cases
      with short limbed dwarfism, of which 13 fetuses were examined after termination
      of pregnancy and two were evaluated postnatally. RESULTS: Short rib dysplasia
      syndromes with or without polydactyly, osteogenesis imperfecta type II,
      thanatophoric dysplasia, campomelic dysplasia, chondrodysplasia punctata,
      rhizomelic type and achondrogenesis were the lethal skeletal dysplasias
      diagnosed. CONCLUSION: Precise identification of the tye of skeletal dysplasia is
      paramount for proper genetic counseling. Postnatal examination and detailed
      radiographic examination of the fetus especially of the pelvis, limbs, skull and
      spine are essential to identify the type of skeletal dysplasia.

PMID- 18057680
TI  - Effect of clofibrate in non-hemolytic indirect hyperbiliru-binemia in full term
      neonates.
AB  - OBJECTIVE: Jaundice is a common clinical problem in neonatal period which may
      result in brain damage even in healthy full term newborns, when it is severe. The
      aim of this study was to characterize the therapeutic effect of clofibrate in
      full term neonates who present with nonhemolytic jaundice. METHODS: A clinical
      controlled study was performed on 60 full term neonates who presented with non-
      hemolytic jaundice. 30 neonates were treated with a single oral dose of
      clofibrate (100 mg/Kg) plus phototherapy (case group), while 30 neonates received
      only phototherapy (control group). Both groups were compared in regard to post
      therapeutic mean total and indirect plasma bilirubin levels, admission duration
      and the rate of exchange transfusion. RESULTS: The reduction rate of total and
      indirect plasma bilirubin levels were significantly higher in the clofibrate-
      treated group as compared with the control group (P< 0.05). The mean duration of
      admission was found to be reduced from 2.9 +/- 0.9 days in the control groupl to
      2.2 +/- 0.6 days in clofibrate- treated group (P=0.002). The mean plasma total
      bilirubin level was lower in the clofibrate- treated group. No cases required
      phototherapy after 48 hour in clofibrate- treated group, while 9 neonates (30%)
      and 2 neonates (6.7%) required phototherapy after 72 hour and 96 hour
      respectively in the control group. There was no difference between both the
      groups for sex, the time of developing jaundice and the rate of exchange
      transfusion. CONCLUSION: A single dose of clofibrate (100 mg/Kg) along with
      phototherapy is more effective than phototherapy alone in treating non-hemolytic
      hyperbilirubinemia in term healthy newborn infants.

PMID- 18057681
TI  - Essential hypertension in early and mid-adolescence.
AB  - OBJECTIVES: To detect prevalence of essential hypertension in early and mid
      adolescents and to identify various risk factors. METHODS: Blood pressure was
      recorded in 503 apparently normal school students in 10 to 16 yr age group as per
      standard guidelines. Detailed clinical examination was done in all cases. A
      detailed questionnaire was sent to parents. RESULTS: 6.16% of adolescents had
      high blood pressure at the end of fourth screening. Both systolic and diastolic
      hypertensions were documented. Increased body mass index and reduced consumption
      of vegetables and fruits were found to be statistically significant risk factors
      for hypertension. CONCLUSION: Multiple blood pressure recordings are essential
      for accurate diagnosis of hypertension. There is a high prevalence of essential
      hypertension amongst adolescents in Mysore city with modifiable risk factors for
      hypertension.

PMID- 18057682
TI  - Pattern of tobacco use among school children in National Capital Territory (NCT).
AB  - OBJECTIVE: To study the prevalence, consumption patterns and correlates of
      tobacco use among adolescent SZI children in Government schools in the National
      Capital territory of Delhi. METHODS: Thirty schools in National Capital Territory
      (NCT) of Delhi, India, were selected by two stage cluster random design and
      population proportionate to size sampling (PPS) methodology. A sample of 3,422
      children in the age group of 10-18 years studying in the 30 middle and senior
      secondary Government schools in NCT of Delhi were studied. Each student was
      administered a pre-tested, semi-structured questionnaire. RESULTS: Overall 9.8%
      of the study children had at least once experimented with any form of tobacco in
      their lifetime. The proportion of children who were current users of tobacco
      products was 5.4% (boys: 4.6%, Girls: 0.8%). Current users differed from
      abstainers in location of their schools, category of school, class, gender,
      hobbies, not having friends, having tobacco users in family and school etc.
      CONCLUSION: Consumption of tobacco amongst adolescents is an emerging health
      problem in Delhi. A number of variables seem to differentiate between the current
      users and abstainers. Tobacco use in family and school environment is a mutable
      factor that should be focused in tobacco reduction campaigns. Encouraging
      friendship has a protective influence. There is a need for similar studies in
      other metropolitan cities of the country.

PMID- 18057683
TI  - Association of HLA-*08:DRB1*03 with immunoglobulin A-deficiency.
AB  - OBJECTIVE: Susceptibility to IgA deficiency (IgAD) is strongly associated with
      alleles of HLA, but it is not equally strong in different human populations.
      Therefore, the goal of this study was to determine the HLA-A, -B and -DRB1
      antigenic and haplotypic frequencies in unrelated Polish Caucasian IgA-deficient
      patients who had never been examined so far in this respect. METHODS: The HLA
      alleles were determined by means of low resolution polymerase chain reaction with
      sequence specific primers (PCR-SSP) method in a group of IgA-deficient patients
      and control subjects from the same area. RESULTS: The HLA-DRB1*03 allele showed
      the strongest association with IgA deficiency in the Polish population (OR=6.6, p
      cor=0.0084). The HLA-B*08 allele was also associated with predisposition to the
      disease (OR=6.22, p cor=0.033). These significant associations could be explained
      in the context of a positive association of IgAD with the HLA-B*08:DRB1*03
      haplotype, previously reported in other Caucasoid populations from Northern and
      Central Europe. In our group the HLA-B*08:DRB1*03 haplotype was present in 52.9%
      of IgA-deficient patients comparing to 9.9% in controls (p< 0.00011). A positive
      association of HLA-B*08 and DRB1*03 was stronger in IgA-deficient males than in
      females from the same group. CONCLUSION: Immunoglobulin A deficiency in Polish
      population is strongly associated with HLA-B*08:DRB1*03 haplotype rather than
      with single alleles.

PMID- 18057685
TI  - Short rib polydactyly syndrome - type 2 (Majewski).
AB  - Short rib polydactyly syndromes (SRPS) are a group of inherited autosomal
      recessive skeletal dysplasias. It is characterized by the triad of micromelia,
      polydactyly and short horizontal ribs with or without visceral involvement. We
      report a case of SRPS-2 in a fresh stillborn and discuss the differential
      diagnosis.

PMID- 18057684
TI  - Ionized magnesium and gestational age.
AB  - OBJECTIVE: Investigation of magnesium (Mg) homeostasis has re-emerged as an area
      of interest in preterm born neonates who are at risk for brain pathology.
      However, data regarding the association between the biologically active ionized
      form of Mg and gestational age (GA) at an early stage of life in newborn infants
      are controversial. METHODS: We evaluated the total and ionized Mg electrolyte
      (TMg and IMg) as well as the calcium (TCa and ICa) and pH in the cord blood and
      on day 2 of life in 22 neonates born at different gestational ages (< 32, 32-34
      and > or =35 week) without magnesium tocolysis and absence of serious
      complications during pregnancy and delivery. RESULTS: The IMg fraction that
      accounted for 68.1+/-5.1% of the TMg in the cord blood and 67.9+/-4.5% of the TMg
      on day 2 of life, was significantly higher in very preterm infants (GA< 32 week)
      as compared to neonates with GA > 35 week. Higher IMg levels were correlated with
      the lower pH that was recorded in the cord blood of the very preterm infants
      (correlation coefficient, r=-0.80, p< 0.0001) and ICa (r = -0.52, P< 0.01). Lower
      pH also was correlated with the GA (P< 0.0001). However, standard multiple
      regression analysis showed significant association between IMg levels and
      decreased pH but not the gestational age or ICa (beta=-1.10+/-0.21, p< 0.00009).
      CONCLUSION: Extremely preterm infants even without additional exposure to
      tocolytic magnesium are at risk for the lower pH associated elevation of ionized
      Mg, which should be considered during the management of these infants in order to
      prevent hypermagnesemia-related pathology.

PMID- 18057686
TI  - Intravenous immunoglobulin therapy of lupus pneumonitis.
AB  - Acute lupus pneumonitis in an 11-year-old girl with lupus nephritis is reported.
      Chest radiograph and arterial blood gas parameters were suggestive of Acute
      Respiratory Distress Syndrome (ARDS). Definitive pulmonary infection was excluded
      by investigations and poor clinical response to antibiotics. The respiratory
      worsening warranted ventilatory support with very high pressures. A trial of
      intravenous immunoglobulin was given following which there was improvement in the
      ventilatory requirements by 36 hours. The child was successfully weaned off
      ventilator and discharged from ICU by day 7. The role of intravenous
      immunoglobulin during acute life threatening pulmonary emergencies in a case of
      SLE prompted this clinical brief.

PMID- 18057687
TI  - Multiple cavernous malformations with supravermian arachnoid cyst.
AB  - Cerebral cavernous malformation are congenital vascular abnormalities that have
      been reported in 0.4% of the population; they represent 5-13% of all
      cerebrovascular malformations. Onset of cerebral cavernous malformations may be
      associated with seizures, intracranial hemorrhages, focal neurological deficit or
      migraine-type headaches. Some patients may require surgical intervention due to
      hemorrhage. Multiple cavernomas in childhood have been reported in the
      literature, but they are rare. This manuscript presents a 12-year-old girl with
      multiple cavernomas accompanied by supravermian arachnoid cyst detected by
      neuroimaging techniques. This is the first report that demonstrates a case of
      pediatric multiple cavernous malformation coexisting with arachnoid cyst of the
      supravermian cistern.

PMID- 18057688
TI  - Transient methemoglobinemia in an infant.
AB  - We report a case of transient methemoglobinemia in an infant due to
      gastroenteritis. Methemoglobinemia should be suspected in infants with a history
      of diarrhea and cyanosis that is out of proportion to the history and clinical
      examination. Methemoglobinemia can be life threatening, but outcome is good when
      treated with IV methylene blue.

PMID- 18057689
TI  - Unilateral palatal palsy with viral hepatitis.
AB  - Isolated unilateral palatal (velopalatopharyngeal) palsy is a clinical rarity.
      This usually presents in a child as acute onset rhinolalia, unilateral absent
      palatal reflex and pharyngeal asymmetry with a benign self-resolving course.
      Etiology remains controversial. We report association of this entity in a male
      child with viral hepatitis A.

PMID- 18057690
TI  - Fatal thyrotoxic periodic paralysis with normokalemia.
AB  - We present a 10-year-old girl who presented to our emergency services with
      difficulty in breathing of 2-days duration and progressive weakness of a month's
      duration. In a previous admission elsewhere, she had not been detected to have
      hyperthyroidism or electrolyte abnormalities. On admission, the child was in
      hypercapnic respiratory failure with tachycardia and hepatomegaly. A small goiter
      as well as signs of thyrotoxicosis were present. Laboratory investigations showed
      anemia, mildly elevated liver enzymes and serum potassium of 4.8mEq/L. Despite
      intubation and ventilation and other supportive management including propranolol,
      the patient could not be saved. Post-mortem biopsy of the thyroid showed diffuse
      hyperplasia of the follicles and muscles showed evidence of thyroid myopathy.

PMID- 18057691
TI  - Hypomelanosis of Ito with cerebral malformation.
AB  - Syndromic forms of cortical maldevelopment continue to be a curiosity.
      Hypomelanosis of Ito (HI) is the presence of whirled hypochromic skin lesions
      often associated with nondermatological manifestations. The polymorphism of brain
      abnormalities associated with HI is well known. We report three cases of
      Hypomelanosis of Ito, occuring in infants and associated with cerebral
      malformation.

PMID- 18057692
TI  - Idiopathic chronic subdural hematoma, MCA infarct and cortical atrophy with
      status epilepticus in infants.
AB  - Spontaneous chronic subdural hematomas in infants are extremely rare. A very
      limited number of cases are known and reported in literature. The clinical
      presentation can be myriad varying from asymptomatic cases to gross neurological
      deficits. We report the cases of 2 infants who presented to us with repeated
      episodes of generalized tonic clonic seizures since birth. No etiology could be
      established for either of them. Subsequent imaging revealed chronic subdural
      hematoma, MCA infarct and cortical atrophy in both the cases. Both the cases
      improved following evacuation of the chronic subdural hematoma. One of the
      infants had secondary craniosynostosis for which additional coronal suturectomy
      had to be done. The management of such cases and a brief review of literature are
      discussed.

PMID- 18057693
TI  - Kawasaki disease with DIC as a complication.

PMID- 18057694
TI  - Hemorrhagic pleural effusion: can it be scurvy?

PMID- 18057695
TI  - PF1270A, B and C, novel histamine H3 receptor ligands produced by Penicillium
      waksmanii PF1270.
AB  - Three novel histamine H3 receptor (H3R) ligands, PF1270A (1), PF1270B (2) and
      PF1270C (3) were isolated from the culture broth of the fungal strain PF1270. The
      strain was identified as Penicillium waksmanii on the basis of morphological
      characteristics. These compounds were obtained from the culture broth by solvent
      extraction and chromatographic purification. Their structures were established by
      spectroscopic methods and X-ray crystallographic analysis. They possess
      pentacyclic spiroindolinone skeletons. 1, 2 and 3 displayed high affinity for the
      rat H3R (Ki=0.058, 0.17 and 0.19 microM, respectively) and human H3R (Ki=0.047,
      0.12 and 0.22 microM, respectively). Moreover, 1, 2 and 3 acted as potent
      agonists with the EC50 values of 0.12, 0.15 and 0.20 microM, respectively.

PMID- 18057696
TI  - Stachybotrydial selectively enhances fibrin binding and activation of Glu
      plasminogen.
AB  - Stachybotrydial, a triprenyl phenol metabolite from a fungus, has a plasminogen
      modulator activity selective to Glu-plasminogen. Stachybotrydial enhanced fibrin
      binding and activation of Glu-plasminogen (2- to 4-fold enhancement at 60-120
      microM) but not of Lys-plasminogen. Approximately 1.2-1.6 moles of
      [3H]stachybotrydial bound to Glu-plasminogen to exert such effects. The selective
      modulation of the Glu-plasminogen function by stachybotrydial may be related to
      alteration of its conformational status.

PMID- 18057697
TI  - Aberrant expression of Fra-1 in estrogen receptor-negative breast cancers and
      suppression of their propagation in vivo by ascochlorin, an antibiotic that
      inhibits cellular activator protein-1 activity.
AB  - Estrogen receptor-negative breast cancers generally are highly malignant,
      resistant to chemotherapy and poorly prognostic. Here we demonstrate that
      estrogen receptor-negative human breast cancer cell lines highly express Fra-1, c
      Fos and c-Jun, components of the transcription factor, activator protein-1 (AP
      1). Retrospective observation of breast cancer tissues obtained by core needle
      biopsy before surgery from stages II and III patients demonstrates that Fra-1
      expression is high in estrogen receptor-negative human breast cancers, and
      negatively correlated to paclitaxel sensitivity. Ascochlorin, which suppresses
      cellular AP-1 activity, selectively kills estrogen receptor-negative human and
      mouse breast cancer cell lines, and prolongs the survival time of mice implanted
      with an estrogen receptor-negative mammary carcinoma. These results suggest that
      chemotherapy targeting AP-1 activity is a potent strategy for estrogen receptor
      negative human breast cancers.

PMID- 18057698
TI  - A-102395, a new inhibitor of bacterial translocase I, produced by Amycolatopsis
      sp. SANK 60206.
AB  - Bacterial phospho-N-acetylmuramyl-pentapeptide translocase (translocase I: EC
      2.7.8.13) is a key enzyme in peptidoglycan biosynthesis, and a known target of
      antibiotics. Here we report a new nucleoside inhibitor for translocase I, A
      102395, isolated from the culture broth of the strain Amycolatopsis sp. SANK
      60206. A-102395 is a new derivative of capuramycin that has the benzene with a
      uniquely substituted chain instead of an aminocaprolactam. A-102395 is a potent
      inhibitor of bacterial translocase I with IC50 value of 11 nM, but possesses no
      antimicrobial activity against various strains tested.

PMID- 18057699
TI  - Xylarinic acids A and B, new antifungal polypropionates from the fruiting body of
      Xylaria polymorpha.
AB  - Two new polypropionates designated as xylarinic acids A and B were isolated from
      the fruiting body of Xylaria polymorpha. Their structures were established as
      4,6,8-trimethyl-2,4-decadienoic acid and 2,4,6-trimethyl-2-octenoic acid,
      respectively, on the basis of extensive spectroscopic analysis. Both compounds
      displayed significant antifungal activity against plant pathogenic fungi Pythium
      ultinum, Magnaporthe grisea, Aspergillus niger, Alternaria panax, and Fusarium
      oxysporium, whereas they did not show antibacterial and cytotoxic effect.

PMID- 18057700
TI  - Analysis of modular-iterative mixed biosynthesis of lankacidin by heterologous
      expression and gene fusion.
AB  - Lankacidin is a unique 17-membered macrocyclic antibiotic different from usual
      even-membered macrolides. Based on the gene organization of the lankacidin
      biosynthetic cluster coded on the linear plasmid pSLA2-L in Streptomyces rochei,
      we previously proposed a hypothesis of modular-iterative mixed polyketide
      biosynthesis for lankacidin. Two experimental evidences in this paper further
      strengthened this hypothesis. Heterologous expression of the lankacidin cluster
      (lkcA-lkcO) in Streptomyces lividans resulted in lankacidinol A production,
      indicating that the gene cluster is sufficient for the synthesis of the
      lankacidin skeleton. In addition, a gene fusant of lkcF and lkcG produced
      lankacidin at a similar level to the parent strain, suggesting that an iterative
      function of the LkcF protein is unlikely. These results are consistent with the
      hypothesis that LkcC is used four times and LkcA, LkcF and LkcG are used
      modularly to accomplish eight condensation reactions leading to the lankacidin
      skeleton.

PMID- 18057701
TI  - In vitro antimicrobial activity of telavancin against methicillin-resistant
      Staphylococcus aureus clinical isolates from Japan (2006).
AB  - In vitro antimicrobial activity of telavancin, a rapidly bactericidal
      lipoglycopeptide, was evaluated against 1500 strains of MRSA recently isolated in
      Japan. Telavancin had potent activity, with MIC values that ranged from 0.12
      microg/ml to 0.5 microg/ml and a MIC90 value of 0.5 microg/ml. The MIC90s of
      vancomycin and linezolid were 1.0microg/ml and 2 microg/ml, respectively. No
      vancomycin intermediate resistant or vancomycin-resistant MRSAs were detected in
      this surveillance study.

PMID- 18057702
TI  - Burkholone, a new cytotoxic antibiotic against IGF-I dependent cells from
      Burkholderia sp.
AB  - In the course of our screening program for new inhibitors of IGF-I signaling, we
      isolated a new cytotoxic antibiotic, burkholone, from the culture broth of
      Burkholderia sp. QN15488. The structure of burkholone was determined to be (E)-3
      methyl-2-(2-octenyl)-4-quinolone by a series of NMR analyses. Burkholone induced
      cell death 32D/GR15 cells with an IC50 value of 160 nM in IGF-I containing
      medium, while no cell death was observed in IL-3 containing medium even at the
      concentration of 37 microM.

PMID- 18057703
TI  - Byelyankacin: a novel melanogenesis inhibitor produced by Enterobacter sp. B20.
AB  - A novel melanogenesis inhibitor, byelyankacin (1), was isolated from the
      fermentation broth of a bacterial strain. The producing organism, designated B20,
      was identified as a member of the genus Enterobacter based on taxonomic
      characteristics. 1 was obtained as a white powder from the culture medium by
      solvent extraction and serial chromatographic purification. The structure of 1
      was determined as (E)-4-(2-isocyanovinyl)phenyl alpha-L-rhamnopyranoside on the
      basis of spectroscopic data. 1 potently inhibited mushroom tyrosinase and
      melanogenesis of B16-2D2 melanoma cells with IC50 value of 2.1 nM and 30 nM,
      respectively.

PMID- 18057704
TI  - Compartmentalized regulations of ion channels in the heart.
AB  - The rate and force of contraction of the heart are precisely controlled by
      compartmentalized regulation of cardiac ion channels which determine electrical
      activities. It is known that modulation of cardiac ion channels, which is caused
      by drug administration, sympathetic nervous system stimulation and gender
      difference, can increase risks of lethal arrhythmias in carriers of inherited
      disease mutations. These modulations are thought to also be involved in common
      cardiac arrhythmias. Because many signaling molecules are localized within single
      cells, an understanding of the molecular basis of compartmentalized regulation of
      cardiac channels is a key for understanding and treating the lethal arrhythmias.
      In this review, I will discuss molecular mechanisms of compartmentalized
      regulation of cardiac ion channels via drugs, cAMP and sex hormones.

PMID- 18057705
TI  - Population pharmacokinetics and proton pump inhibitory effects of intravenous
      lansoprazole in healthy Japanese males.
AB  - A total of 56 healthy Japanese males were enrolled in single- or multiple- dose
      pharmacokinetic trials of intravenous lansoprazole administration. The population
      pharmacokinetics of the drug was evaluated using nonlinear mixed effects model
      (NONMEM) software. In addition, the effect of CYP2C19 polymorphism on proton pump
      inhibition by lansoprazole was investigated using 24-h intragastric pH monitoring
      in the 32 subjects. Time course of serum lansoprazole concentration following
      intravenous short infusion was well described by a 2-compartment model. The mean
      volume of the central and peripheral compartments was 0.110 and 0.201 l/kg,
      respectively. The mean inter-compartment clearance was estimated to be 0.0882
      l/h/kg. The population mean value of systemic clearance in the homoEM (CYP2C19 1/
      1), heteroEM (CYP2C19 1/2 and 1/3), and PM (CYP2C19 2/2, 2/3, and 3/3) groups was
      0.179, 0.109, and 0.038 l/h/kg, respectively. The mean intragastric pH following
      twice-daily doses of 30 mg lansoprazole was approximately 6, 5, and 4 in the PM,
      heteroEM, and homoEM groups, respectively. These findings indicate that large
      interindividual variability exists in the pharmacokinetics of intravenously
      administered lansoprazole, but that twice-daily infusion of a 30 mg dose leads to
      significant and sustained proton pump inhibition, even in the homoEM group,
      despite the short elimination half-life of the drug.

PMID- 18057706
TI  - Betaine modulates age-related NF-kappaB by thiol-enhancing action.
AB  - Depletion of glutathione levels and perturbations in redox status are considered
      to play a crucial role in aging and chronic inflammatory processes through the
      activation of redox sensitive transcription factors, including nuclear factor
      kappaB (NF-kappaB). In the current study, we assessed the regulatory action of
      dietary betaine in the suppression of NF-kappaB by comparing kidney tissue from
      old, betaine-supplemented rats or non-betaine-supplemented rats (age 21 months)
      and 7 month-old rats. In addition, cultured HEK 293T cells were utilized for the
      molecular assessment of betaine's restorative ability of redox status when
      treating cells with potent glutathione (GSH)-depleting agents. Results showed
      that in old rats a short-term feeding (10 d) with betaine attenuated the age
      related decrease in thiol levels, increase in reactive species and TNFalpha
      expression via NF-kappaB activation, compared to the young controls. These
      findings were verified in the cell-cultured system. Further investigations found
      that redox imbalance due to thiol depletion caused increased NF-kappaB
      activation, and cyclooxygenase (COX)-2 and TNFalpha levels, both of which were
      suppressed by betaine treatment. Based on both in vivo and in vitro data, we
      concluded that betaine exerts its efficacy by maintaining thiol status in the
      regulation of COX-2 and TNFalpha via NF-kappaB activation during aging.

PMID- 18057707
TI  - Chotosan enhances macrophage colony-stimulating factor mRNA expression in the
      ischemic rat brain and C6Bu-1 glioma cells.
AB  - Macrophage colony stimulating factor (M-CSF) is a cytokine which has been
      recently reported to have a neuroprotective effect on ischemic rat brain. In this
      study, we investigated the effect of chotosan, an oriental medicine, which has
      been clinically demonstrated to be effective for the treatment of vascular
      dementia, on M-CSF gene expression in rats with permanent occlusion of bilateral
      common carotid arteries (P2VO) in vivo and in a C6Bu-1 glioma cell line in vitro.
      The expression level of M-CSF mRNA in the cerebral cortices of P2VO rats was
      significantly higher than that in the cerebral cortices of sham-operated animals.
      Repeated treatment of P2VO rats with chotosan (75 mg/kg per day) for 4 d after
      P2VO significantly increased the expression level of M-CSF mRNA in the cortex but
      it had no effect on the expression of beta-actin, granulocyte colony stimulating
      factor (G-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF) mRNAs.
      Moreover, the present in vitro studies revealed that chotosan treatment (10-100
      mug/ml) of C6Bu-1 glioma cells dose-dependently enhanced M-CSF mRNA expression
      without affecting the expression of G-CSF, GM-CSF, and inducible nitric oxide
      synthase mRNAs. The effect of chotosan was reversed by Ro 31-8220 (1 muM), a
      selective protein kinase C (PKC) inhibitor, but not by H-89 (10 muM), a selective
      protein kinase A (PKA) inhibitor. These findings suggest that the upregulatory
      effect of chotosan on M-CSF mRNA expression involves PKC and may play an
      important role in the anti-vascular dementia action of this formula.

PMID- 18057708
TI  - Morphine inhibits erythrocyte carbonic anhydrase in vitro and in vivo.
AB  - Morphine is implicated in diverse functions, from development to immune
      modulation in the central and peripheral nervous systems. At the present time,
      morphine is one of the most effective antinociceptive agents used to manage pain.
      It has been used extensively in the clinical management of pain due to its potent
      analgesic effect. In this study, the in vitro and in vivo inhibitory effects of
      morphine on erythrocyte carbonic anhydrase (CA) were investigated. Human
      erythrocyte isoenzymes, HCA-I and HCA-II, were purified by Sepharose-4B affinity
      chromatography column with a yield of 66.95 and 62.82%, a specific activity of
      3892.3 and 11663.2 EU/mg proteins with 745.1 and 2232.6-fold purification of each
      isoenzyme, respectively. To determine enzyme purity, sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) was performed. In vitro inhibition
      of erythrocyte HCA-I and HCA-II by morphine using the CO(2)-hydratase enzyme gave
      IC(50) values 4.50 x 10(-5) M (r(2): 0.954) and 9.23 x 10(-5) M (r(2): 0.996),
      respectively. CA activity was significantly attenuated in vivo in Spraque-Dawley
      rats for up to 3 h (p<0.001) following intraperitoneal administration of
      morphine. In conclusion, morphine inhibited CA activity both in vitro and in
      vivo.

PMID- 18057709
TI  - Cloning and functional analysis of a novel aldo-keto reductase from Aloe
      arborescens.
AB  - A novel aldo-keto reductase (AKR) was cloned and sequenced from roots of Aloe
      arborescens by a combination of RT-PCR using degenerate primers based on the
      conserved sequences of plant polyketide reductases (PKRs) and cDNA library
      screening by oligonucleotide hybridization. A. arborescens AKR share similarities
      with known plant AKRs (40-66% amino acid sequence identity), maintaining most of
      the active-site residues conserved in the AKR superfamily enzymes. Interestingly,
      despite the sequence similarity with PKRs, recombinant enzyme expressed in
      Escherichia coli did not exhibit any detectable PKR activities. Instead, A.
      arborescens AKR catalyzed NADPH-dependent reduction of various carbonyl compounds
      including benzaldehyde and DL-glyceraldehyde. Finally, a homology model on the
      basis of the crystal structure of Hordeum vulgare AKR predicted the active-site
      architecture of the enzyme.

PMID- 18057710
TI  - The effects of quercetin on antioxidant status and tumor markers in the lung and
      serum of mice treated with benzo(a)pyrene.
AB  - Chemoprevention has emerged as a very effective preventive measure against
      carcinogenesis. Several bioactive compounds present in fruits and vegetables have
      revealed their cancer curative potential on benzo(a)pyrene (B(a)P) induced
      carcinogenesis. In the present study, the efficacy of quercetin on the level of
      lipid peroxides, activities of antioxidant enzymes and tumor marker enzymes in
      B(a)P induced experimental lung carcinogenesis in Swiss albino mice was assessed.
      In lung cancer bearing animals there was an increase in lung weight, lipid
      peroxidation and marker enzymes such as aryl hydrocarbon hydroxylase, gamma
      glutamyl transpeptidase, 5'-nucleotidase, lactate dehydrogenase and adenosine
      deaminase with subsequent decrease in body weight and antioxidant enzymes
      superoxide dismutase, catalase, glutathione peroxidase, glutathione-S
      transferase, glutathione reductase, reduced glutathione, vitamin E and vitamin C.
      Quercetin supplementation (25 mg/kg body weight) attenuated all these
      alterations, which indicates the anticancer effect that was further confirmed by
      histopathological analysis. Overall, the above data shows that the anticancer
      effect of quercetin is more pronounced when used as an chemopreventive agent
      rather than as a chemotherapeutic agent against B(a)P induced lung
      carcinogenesis.

PMID- 18057711
TI  - Chemically modified heparin inhibits mesangial cell proliferation induced by high
      glucose through interfering with the cell cycle.
AB  - The aims of this study were to investigate whether chemically modified non
      anticoagulation heparin derivate (Periodate-Oxidized/Borohydride-Reduced modified
      heparin (OR-heparin)) can inhibit high glucose-induced human mesangial cell
      proliferation and its influence on the cell cycle. OR-heparin with low
      anticoagulation activity inhibited high glucose-induced early proliferation in a
      dose-dependent manner. OR-heparin released high glucose-arrested mesangial cells
      at G(1) phase, and dose-dependently increased S phase. OR-heparin also inhibited
      high glucose-activated ERK1/2 phosphorylation, induced p27(Kip1) expression, and
      suppressed reactive oxygen species (ROS) accumulation in a dose-dependent manner.
      Our results suggest that OR-heparin releases high glucose-arrested cells on G(1)
      phase and inhibits high glucose-induced mesangial cell proliferation through
      blocking ERK1/2 phosphorylation and delaying S phase progression, which may be in
      correlation with OR-heparin suppressing ROS accumulation.

PMID- 18057712
TI  - The effect of survivin on multidrug resistance mediated by P-glycoprotein in MCF
      7 and its adriamycin resistant cells.
AB  - Although anticancer chemotherapeutic drugs have been designed to inhibit the
      growth of tumor cells, chemotherapy frequently fails due to the development of
      multidrug resistance (MDR). In this paper, the effect of survivin on multidrug
      resistance mediated by P-glycoprotein (Pgp) was investigated in breast cancer
      cells. Overexpression of survivin in MCF-7 cells transfected with survivin
      expression vector pEGFP/survivin results in decreasing sensitivity to anticancer
      drugs and activation of Pgp to export drug out of cells. Down regulation of
      survivin in MCF-7/adriamycin (ADR) transfected with RNAi directed against
      survivin vector psh1/survivin could increase the drug accumulation in cells by
      inhibiting Pgp. Downregulation of the expression of the Pgp with the specific
      inhibitor verapamil could markedly suppress the survivin mRNA expression, whereas
      the reverse impact was not observed. Survivin might modulate the turnover of Pgp
      or transport by Pgp in cells, which result in anti-apoptosis and drug resistance.
      Our results suggest that survivin might play a key role in MDR in the presence of
      Pgp, and this might represent a novel strategy for modulating MDR in cancer
      cells.

PMID- 18057713
TI  - Protein O-N-acetylglucosaminylation modulates promoter activities of cyclic AMP
      response element and activator protein 1 and enhances E-selectin expression on
      HuH-7 human hepatoma cells.
AB  - High glucose accelerates O-N-acetylglucosaminylation (O-GlcNAcylation) of
      proteins and causes diabetic complications. In the present study, we found that
      treatment of HuH-7 human hepatoma cells with high glucose or the protein O-N
      acetylglucosaminidase (O-GlcNAcase) inhibitor O-(2-acetoamide-2-deoxy-D
      glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) increased the cell surface
      expression of E-selectin. A dual luciferase reporter assay indicated that high
      glucose and PUGNAc suppressed promoter activities of the cyclic AMP response
      element (CRE) and enhanced those of activator protein 1 (AP-1). Enhanced CRE
      promoter activities in HuH-7 cells treated with dibutyryl cAMP or co-transfected
      with a protein kinase A expression vector pFC-PKA that enhances the
      phosphorylation of CRE binding protein (CREB) were suppressed by PUGNAc. In
      contrast, PUGNAc further increased the enhanced AP-1 promoter activity in cells
      transfected with a mitogen-activated protein kinase kinase kinase expression
      vector pFC-MEKK that enhances c-Jun phosphorylation. Immuno-blotting using an
      anti-O-GlcNAc antibody revealed that high glucose and PUGNAc accelerated protein
      O-GlcNAcylation and that there were substantial differences in the O-GlcNAcylated
      proteins in the cytoplasmic and nuclear fractions. In addition, PUGNAc increased
      the nuclear import of O-GlcNAcylated CREB. These results suggest that protein O
      GlcNAcylation modulates the promoter activities of E-selectin gene, suppression
      of CRE and enhancement of AP-1, and enhances E-selectin protein expression on
      hepatocytes.

PMID- 18057714
TI  - Induction of apoptosis by the licochalcone E in endothelial cells via modulation
      of NF-kappaB and Bcl-2 Family.
AB  - Licochalcones have a variety of biological properties including anti-tumor, anti
      parasitic and anti-bacterial activities. Recently, a new retrochalcone
      (licochalcone E, Lico-E) was isolated from the roots of Glycyrrhiza inflata
      (Chem. Pharm. Bull., 53, 2005, Yoon et al.) by cytotoxicity-guided fractionation.
      This study examined whether or not Lico-E-induced endothelial cell death occurs
      through apoptosis, and investigated molecular mechanisms involved in this
      process. Lico-E was found to suppress ECV304 cell growth and induce apoptosis.
      The induction of apoptosis by Lico-E was confirmed by the ladder-patterned DNA
      fragmentation, the presence of cleaved and condensed nuclear chromatin and the
      increased number of annexin V-positive cells. Lico-E could effectively inhibit
      the constitutive NF-kappaB activation, as revealed by the electrophoretic
      mobility shift assay and NF-kappaB-dependent luciferase reporter study. In
      addition, the Lico-E treatment caused a change in the Bax/Bcl-2 ratio that
      favored apoptosis. These results suggest that Lico-E induces endothelial cell
      apoptosis by modulating NF-kappaB and the Bcl-2 family.

PMID- 18057715
TI  - Analyses of novel prognostic factors in neuroblastoma patients.
AB  - Neuroblastoma (NB) is the most common malignant solid tumor in childhood. There
      are well-recognized prognostic factors in NB such as age at diagnosis, organ of
      origin, stages, MYCN gene amplification, and expression of H-ras, trkA and
      survivin. Moreover, we investigated the expression of vascular endothelial growth
      factor (VEGF), tyrosine hydroxylase (TH), p53, stem cell factor (SCF) and c-kit
      of its receptor with quantitative real-time polymerase chain reaction (PCR) in 22
      NBs and 4 other tumors (one malignant lymphoma, one malignant teratoma, and 2
      rhabdomyosarcomas) samples. The correlation between patients' prognoses and the
      expression of TH or c-kit was newly recognized, particularly the good prognosis
      in patients in whom c-kit highly expressed and the poor prognosis contrarily
      associated with low or no expression, although the SCF of its ligand had no
      relationship with patient prognosis. It is possible that tumors without c-kit
      expression can not react with SCF (via the autocrine or paracrine system) and
      remain immature. It may be that this is a new critical clinical event in NB
      patients.

PMID- 18057716
TI  - Proteomic characterization of angiogenic endothelial cells stimulated with cancer
      cell-conditioned medium.
AB  - To characterize the protein expression profiles and identify the molecules
      associated with tumor angiogenesis, the cellular proteins of human umbilical vein
      endothelial cells (HUVECs) in response to cancer cell-conditioned medium (CM)
      prepared from HT1080 human fibrosarcoma cells were analyzed using fluorescence
      labeled 2D gel-based proteomics. Most differentially expressed proteins in HT1080
      CM-stimulated cells were found to be downregulated (88%) rather than upregulated
      (12%) based on statistical analysis of protein spot signals. Additionally, we
      examined the effects of vascular endothelial cell growth factor (VEGF), a
      proangiogenic factor, on cellular protein expression. In contrast, most
      differentially expressed proteins were found to be upregulated (59%) rather than
      downregulated (41%) in VEGF-stimulated HUVECs. Comparative analyses of 29 and 35
      protein species identified in CM-stimulated and VEGF-stimulated HUVECs,
      respectively, revealed the remarkable differences between these two stimulations.
      Only four proteins were differentially expressed by both treatments: annexin A2,
      enolase 1, and T-plastin (downregulated by CM but upregulated by VEGF), and RAN
      (downregulated by both CM and VEGF). These findings provide new information
      regarding the regulation of protein expression associated with tumor
      angiogenesis.

PMID- 18057717
TI  - Induction and high density culture of human hepatoblasts from fetal hepatocytes
      with suppressing transformation.
AB  - It is well known that it would be important to cultivate human hepatocytes of
      about 10(10) cells at a high cell density, about 1 x 10(7) cells/cm(3), in the
      bioreactor for the development of bioartificial liver. However, since primary
      human hepatocytes lack an ability to proliferate in vitro, it is essential to
      establish a culture method for the proliferation of normal human hepatic stem
      cells as a cell source. In this study, it was found that human hepatoblasts, a
      kind of hepatic stem cells, were induced from human fetal hepatocytes while
      keeping the ability of proliferation by the treatment of 1mM sodium butyrate (SB)
      for 12 d of culture. The transformation of hepatoblasts was evaluated by abnormal
      prothrombin (PIVKA-II) assay, which is a clinical marker for hepatocellular
      carcinoma. The PIVKA-II production rate of the cells was suppressed to the normal
      level under 1 mM SB. The cells including hepatoblasts under 1 mM SB attached to
      the porous hydroxyapatite carriers and proliferated to a high cell density of
      about 1 x 10(7) cells/cm(3) in the carriers. The liver-specific function,
      cytochrome P450 3A4 activity (4.2 pmol/mg protein/min) of the cells in the
      carriers under 1 mM SB was comparable to that of primary human hepatocytes.
      Ammonia metabolizing activity (0.21 micromol/10(6) cells/h) of the cells was also
      comparable to that of porcine hepatocytes used in the bioartificial liver. The
      PIVKA-II production rate of the cells in the carrier was suppressed to the normal
      level. These results suggested that induction of human hepatoblasts from fetal
      hepatocytes by the treatment of 1mM SB and proliferation of the cells at a high
      cell density using hydroxyapatite carriers should be one of the more promising
      culture methods for bioartificial liver developments.

PMID- 18057718
TI  - Lincomycin protects mice from septic shock in beta-glucan-indomethacin model.
AB  - We have developed a septic shock model in mice by sequential administration of
      beta-glucan, a biological response modifier, and indomethacin (IND), a
      nonsteroidal anti-inflammatory drug. Lethality was significantly related to the
      translocation of gut flora to various organs and mal-adjustment of the cytokine
      network. In the present study, we have examined the effect of antibiotics on this
      model to further clarify meanings of microbial flora. Schizophyllan (SPG),
      antitumor beta-glucan for clinical use, obtained from the culture filtrate of
      Schizophyllum commune, was used to induce sepsis. Lincomycin (LCM), imipenem
      (IPM), cilastatine (CS), and ampicillin (ABPC) were used for antibiotics
      treatment. The survival rate of SPG/IND-treated mice was significantly increased
      by administering LCM or ABPC/IPM/CS, and the effect was more significant by LCM.
      In in vitro spleen cell culture, LCM decreased proinflammatory cytokine
      production. Moreover, prednisolone, immune suppresser treatment improved survival
      of SPG/IND-treated mice. These findings suggest that LCM is an effective
      antibiotic in this endogenous septic model by modulating gut microbial flora and,
      at least a part, by regulating cytokine production of leukocytes.

PMID- 18057719
TI  - Comparative study on nobiletin metabolism with liver microsomes from rats, Guinea
      pigs and hamsters and rat cytochrome p450.
AB  - In vitro metabolism of nobiletin, a polymethoxy-flavonoid abundantly present in
      citrus peels, was studied using liver microsomes of rats, hamsters and guinea
      pigs and ten cDNA-expressed rat cytochrome P450 (P450). The effects of P450
      inducers on nobiletin metabolism were also investigated. Aerobical incubation
      with NADPH and animal liver microsomes transformed nobiletin to five metabolites,
      M-1, M-2, M-3, M-4 and M-5. From LC-MS and (1)H-NMR data and a time-course study,
      these were assumed to be 4'-hydroxy (OH)-, 7-OH-, 6-OH-, 3',4'-diOH- and 6,7-diOH
      metabolites, respectively. Pretreatment of animals with phenobarbital increased M
      2 and M-3 to about 2-fold that in untreated animals. Pretreatment with 3
      methylcholanthrene (MC) resulted in remarkable increases of both M-1 and M-4 (3
      to 9-fold that of untreated). Males had 2-3 times higher M-2 and M-3 formation
      activities in rats, and for M-2 in hamsters than did females. Immunoinhibition
      study using antiserum against P450 revealed the involvement of hamster CYP1A2 in
      the formation of M-1 and M-4 in hamster liver. Of ten rat P450s, CYP2C11, CYP3A1,
      CYP3A2 and CYP2D1 had high activities for the formation of M-1, M-2 and M-3.
      Another P450s (CYP1A1, CYP2C12 and CYP1A2) also showed activity for the formation
      of M-1. Only CYP1A1 produced 3',4'-diOH-metabolites (M-4). However, CYP2A1,
      CYP2B1 and CYP2E1 had no activity for nobiletin. These results suggested that
      constitutive P450s such as CYP2C11, CYP2D1, CYP3A1, CYP3A2 and CYP2C12 are
      responsible for the demethylation at the 6-, 7-, 3'- and 4'-positions; whereas,
      MC-inducible P450s, CYP1A1 and CYP1A2, preferentially catalyzed demethylation at
      the 3'-and 4'-positions.

PMID- 18057720
TI  - Effects of intravenously and orally administered solifenacin succinate (YM905) on
      carbachol-induced intravesical pressure elevation and salivary secretion in mice.
AB  - Solifenacin succinate is a novel muscarinic receptor antagonist used for the
      treatment of overactive bladder (OAB). We investigated the effects of solifenacin
      by oral and intravenous administration on carbachol (CCh)-induced intravesical
      pressure (IVP) elevation and compared its efficacy with that on CCh-induced
      salivary secretion in anesthetized mice. Additionally, we also investigated the
      change in effects between single and repeated oral administration of solifenacin
      on CCh-induced IVP elevation. Results showed that intravenous administration of
      solifenacin dose-dependently inhibited the IVP elevation and salivary secretion.
      The ratio of bladder response to salivary response (ratio of ID(50) values) was
      2.1. Oral administration of solifenacin (0.3-30 mg/kg) also inhibited CCh-induced
      IVP elevation and salivary secretion. Although inhibition of these responses by
      solifenacin (10, 30 mg/kg) was comparable at early time points (0.5 and 1 h after
      administration at 10 mg/kg and 0.5 to 2 h after administration at 30 mg/kg),
      inhibition of CCh-induced IVP elevation was stronger at later time points (2 to 8
      h after administration at 10 mg/kg and 4 to 24 h after administration at 30
      mg/kg). No significant difference in ID(50) values for IVP elevation was observed
      between single and repeated (11 d) oral administration of solifenacin (1-30
      mg/kg), suggesting no change in efficacy on chronic administration. In
      conclusion, intravenous and oral solifenacin inhibits CCh-induced IVP elevation
      more potently than salivary secretion. These results provide further evidence for
      the clinical use of solifenacin as a promising therapeutic drug for OAB with a
      low incidence of dry mouth.

PMID- 18057721
TI  - In vitro screening of psychoactive drugs by [(35)S]GTPgammaS binding in rat brain
      membranes.
AB  - We constructed a reproducible, simple, and small-scale determination method of
      the psychoactive drugs that acted directly on the monoamine receptor by measuring
      the activation of [(35)S]guanosine-5'-O-(3-thio)-triphosphate binding to guanine
      nucleotide-binding proteins (G proteins). This method can simultaneously measure
      the effects of three monoamines, namely dopamine (DA), serotonin (5-HT), and
      norepinephrine (NE), in rat brain membranes using a 96-well microplate.
      Activation of D(1) and D(2) receptors in striatal membranes by DA as well as 5-HT
      and NEalpha(2) receptors in cortical membranes could be measured. Of 12 tested
      phenethylamines, 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,5-dimethoxy-4
      ethylphenethylamine (2C-E), and 2,5-dimethoxy-4-iodophenethylamine (2C-I)
      stimulated G protein binding. The other phenethylamines did not affect G protein
      binding. All 7 tryptamines tested stimulated G protein binding with the following
      rank order of potency; 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)>5-methoxy-N,N
      diallyltryptamine (5-MeO-DALT)>5-methoxy-alpha-methyltryptamine (5-MeO-AMT)>or=5
      methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT)>5-methoxy-N,N
      diisopropyltryptamine (5-MeO-DIPT)>N,N-dipropyltryptamine (DPT)>or=alpha
      methyltryptamine (AMT). This assay system was able to designate psychoactive
      drugs as prohibited substances in accordance with criteria set forth by the Tokyo
      Metropolitan government.

PMID- 18057722
TI  - Chemoimmunotherapeutic approach to prolonged survival time in combination with
      immunization and glutamic Acid derivatives with antitumor activity in tumor
      bearing mice.
AB  - Cancer is one of the major causes of death. For cancer, the general conventional
      treatment and standard of care for clinical oncology remains surgery followed by
      radiation and/or systemic chemotherapy as deemed appropriate based on the
      clinical findings. Chemoimmunotherapy is an approach to treat cancer where
      chemotherapy is given along with immunotherapy. Chemoimmunotherapy may be useful
      to enhance survival time in cancer by improve immunity of the patients. This
      approach may enhance the therapeutic efficacy. A comparative study was done to
      assess the therapeutic efficacy of the whole cell vaccine and the tumor extract
      with or without combination chemotherapy with the synthesized glutamine and
      glutamic acid derivatives and analogs as well as the standard drug etoposide
      against Ehrlich Ascites Carcinoma (EAC) cells in Swiss Albino mice. The study
      showed promising results with the compound 5-N-n-hexyl-2-(4-iso
      butylbenzenesulphonyl)glutamine. The compound when combined with the whole cell
      vaccine as well as the tumor extract increases the survival time and the
      therapeutic efficacy which is comparable with that of standard drug etoposide.

PMID- 18057723
TI  - Ginkgolide C inhibits platelet aggregation in cAMP- and cGMP-dependent manner by
      activating MMP-9.
AB  - In this report, we investigated the effect of ginkgolide C (GC) from Ginkgo
      biloba leaves in collagen (10 mug/ml)-stimulated platelet aggregation. It has
      been known that matrix metalloproteinase-9 (MMP-9) is released from human
      platelets, and that it significantly inhibited platelet aggregation stimulated by
      collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by
      GC to form an activated MMP-9 (86-kDa) on gelatinolytic activities. And then, GC
      dose-dependently inhibited platelet aggregation, intracellular Ca(2+)
      mobilization, and thromboxane A(2) (TXA(2)) formation in collagen-stimulated
      platelets. In addition, GC significantly increased the formation of cyclic
      adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which
      have an anti-platelet function in both resting and collagen-stimulated platelets.
      Therefore, we demonstrate that the inhibitory effect of GC on platelet
      aggregation might be involved into the following pathways. GC may increase
      intracellular cAMP and cGMP production and MMP-9 activity, inhibit intracellular
      Ca(2+) mobilization and TXA(2) production, thereby leading to inhibition of
      platelet aggregation. These results strongly indicate that GC is a potent
      inhibitor of collagen-stimulated platelet aggregation. It may be a suitable tool
      for a negative regulator during platelet activation.

PMID- 18057724
TI  - Inhibition of LPS-induced iNOS, COX-2 and cytokines expression by poncirin
      through the NF-kappaB inactivation in RAW 264.7 macrophage cells.
AB  - We previously reported that poncirin, a flavanone glycoside isolated from the
      EtOAc extract of the dried immature fruits of Poncirus trifoliata, is an anti
      inflammatory compound that inhibits PGE(2) and IL-6 production. The present work
      was undertaken to investigate the molecular actions of poncirin in RAW 264.7
      macrophage cell line. Poncirin reduced lipopolysaccharide (LPS)-induced protein
      levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and
      the mRNA expressions of iNOS, COX-2, tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) in a concentration-dependent manner, as determined by
      Western blotting and RT-PCR, respectively. Furthermore, poncirin inhibited the
      LPS-induced DNA binding activity of nuclear factor-kappaB (NF-kappaB). Moreover,
      this effect was accompanied by a parallel reduction in IkappaB-alpha degradation
      and phosphorylation that in by nuclear translocations of p50 and p65 NF-kappaB
      subunits. Taken together, our data indicate that anti-inflammatory properties of
      poncirin might be the result from the inhibition iNOS, COX-2, TNF-alpha and IL-6
      expression via the down-regulation of NF-kappaB binding activity.

PMID- 18057726
TI  - Electrophysiological characterization of tight junctional pathway of rabbit
      cornea treated with ophthalmic ingredients.
AB  - The purpose of this study was to investigate the continuous and real-time
      influence of ophthalmic ingredients on rabbit cornea by monitoring
      electrophysiological characteristics. The tight junctional permeabilities of FITC
      dextran 4,400 (FD-4) was also determined through the cornea in the presence of
      ophthalmic ingredients. Intact cornea showed approximately one k-ohmxcm(2) of
      transepithelial electrical resistance (TEER) and extremely low permeability of FD
      4. The ophthalmic ingredients used in the present study were benzalkonium
      chloride (BK; 0.002%, 0.01%, 0.05%), ethylenediaminetetraacetic acid (EDTA;
      0.5%), capric acid (C10; 0.25%), saponin (SP; 0.1%), taurocholic acid (TA; 1.0%)
      and sodium dodecyl sulfate (SDS; 0.01%). They were previously reported to be
      effective on corneal penetrations of various drugs at those concentrations
      without severe toxicity. These ingredients decreased TEER and increased corneal
      permeability of FD-4. BK reduced TEER in a concentration-dependent manner. There
      was a significant correlation (gamma=0.860) between the permeability coefficient
      (Papp) of FD-4 and conductance (Gm), which is the reciprocal value of TEER. It
      was also indicated that Papp and Gm have a relationship with the corneal
      cytotoxicity of the ingredients. In conclusion, an electrophysiological method
      using isolated cornea was very useful to determine the continuous and real-time
      influence of ophthalmic ingredients on the cornea. In this method,
      electrophysiological conductance must be able to predict corneal tight junction
      permeability and the corneal cytotoxicity of ingredients.

PMID- 18057725
TI  - The chemopreventive effects of Saussurea salicifolia through induction of
      apoptosis and phase II detoxification enzyme.
AB  - The ethanol extract of the aerial part of the Mongolian medicinal plant Saussurea
      salicifolia induced a dose-dependent cell growth inhibition in both human gastric
      adenocarcinoma AGS cells and mouse hepatoma Hepa 1c1c7 cells (IC(50)=30.22 and
      116.96 mug/ml), respectively. The extract induced an apoptosis in AGS cells
      inference from the externalization of the phosphatidylserine, the increase of the
      sub G0/G1 content (%) and the apoptotic morphological changes including membrane
      blebbing, the formation of apoptotic bodies and chromatin condensation. In order
      to identify active substances causing the apoptosis, we further isolated major
      compounds present in Saussurea salicifolia and 7 compounds were isolated
      including a sesquiterpene lactone, cynaropicrin, 3 lignans (trachelogenin,
      matairesinol and arctigenin) and 3 lignan glycosides (tracheloside,
      matairesinoside and arctiin). In general the lignan aglycones were more cytotoxic
      than their lignan glycosides in both AGS cells and Hepa 1c1c7 cells. Cynaropicrin
      not only showed the most potent cytotoxicity among the 7 major compounds but also
      it induced an apoptosis and a weak G2/M arrest in AGS cells. Arctigenin had the
      second-best cytotoxicity among 7 major compounds, and induced an apoptosis. In
      order to evaluate the induction of the phase II detoxification enzyme, we
      measured the induction of quinone reductase activity of the extract, fractions
      and compounds in Hepa 1c1c7 cells. The ethyl acetate fraction and arctigenin
      showed the strongest cancer chemopreventive activity (chemoprevention index=9.88
      and 7.57, respectively). These data suggest that the extract as well as the
      lignan compounds (especially arctigenin) originated from Saussurea salicifolia
      may be served as potential cancer chemopreventive agents for prevention or
      treatment of human cancers.

PMID- 18057727
TI  - Relationship between drug release of DE-310, macromolecular prodrug of DX-8951f,
      and cathepsins activity in several tumors.
AB  - DE-310 is composed of the topoisomerase-I inhibitor DX-8951 (exatecan) and
      carboxymethyldextran polyalcohol (CM-Dex-PA) carrier, which are covalently linked
      via peptidyl spacer (Gly-Gly-Phe-Gly). In this study, we investigated
      relationship between the cathepsin activity and the drug release of DE-310 by use
      of human liver origin cathepsin (B, L and H) and tumor cells (murine tumor cells
      (Meth A and M5076), and human tumor cells (HCT116, A549, PC-12, T98G, and HL
      60)). Preliminary studies indicated that human liver cathepsin B produced Glycyl
      DX-8951 (G-DX-8951) from DE-310 more preferentially than DX-8951, whereas human
      liver cathepsin L produced DX-8951 preferentially. Release of drugs from DE-310
      and cathepsin activities were measured in tumor cell types. The release of both
      DX-8951 and G-DX-8951 from DE-310 correlated well with cathepsin B activity of
      tumor cells. The release of DX-8951 was weakly, but not significantly, correlated
      with cathepsin L activity. In M5076 (high cathepsin activity) or Meth A (low
      cathepsin activity) xenograft models, the levels of DX-8951 and G-DX-8951 in
      M5076 were higher than in Meth A after single intravenous administration of DE
      310. Our findings suggest that cathepsin B is primarily responsible for drug
      release from DE-310 in tumor.

PMID- 18057728
TI  - Association of cumulative cyclosporine dose with its irreversible nephrotoxicity
      in Japanese patients with pediatric-onset autoimmune diseases.
AB  - Cyclosporine (CsA)-induced nephrotoxicity can become a major obstacle to
      continuous use. The aim of this study was to optimize CsA dose to avoid its
      irreversible nephrotoxicity. Twenty-three Japanese patients with pediatric-onset
      systemic lupus erythematosus or idiopathic nephrotic syndrome, who were
      maintained in a stable condition by oral dosing of CsA microemulsion, were
      enrolled in this study. The patients were stratified into 3 groups; those with
      no, reversible, and irreversible nephrotoxicity, according to periodically
      performed renal pathohistological examinations. A higher concentration of CsA in
      blood (p=0.002-0.011) and a longer duration of CsA treatment (p=0.002) were risk
      factors for irreversible nephrotoxicity, and the cumulative CsA dose, the product
      of the maintenance dose and duration of CsA treatment, was predictive of
      nephrotoxicity (p=0.036). The maximum target blood concentration at 2 h post
      dose, C(2), to avoid CsA-induced irreversible nephrotoxicity was 700 ng/ml,
      although the cumulative CsA dose of 4850 mg/kg would result in a 50% probability
      of nephrotoxicity.

PMID- 18057729
TI  - Effects of 3-methyl-4-nitrophenol on the suppression of adrenocortical function
      in immature male rats.
AB  - In previous studies, we found that 3-methyl-4-nitrophenol (4-nitro-m-cresol;
      PNMC) isolated from diesel exhaust particles, and also a degradation product of
      the insecticide fenitrothion, exhibited testicular toxicity in the male of both
      immature rat and adult Japanese quail. It is well established that a functional
      relationship exists between the gonads and adrenals. The present study
      investigates the effect of PNMC on the adrenocortical functions of immature male
      rats. We subcutaneously injected 28-d-old rats with PNMC (1, 10 or 100 mg/kg)
      daily for 5 d. The adrenal glands weights significantly decreased in rats treated
      with 10 or 100 mg/kg PNMC. Plasma concentrations of adrenocorticotropic hormone
      (ACTH) were significantly increased in animals treated with 100 mg/kg PNMC. In
      contrast, plasma concentrations of corticosterone were significantly decreased in
      all PNMC-treated groups, and plasma concentrations of progesterone were
      significantly decreased in rats treated with 10 or 100 mg/kg PNMC. To investigate
      the direct effects of PNMC on the secretion of ACTH from the anterior pituitary
      gland, and on the secretion of corticosterone from the adrenal, we exposed
      cultured primary anterior pituitary and adrenal cells to PNMC (10(-8), 10(-7),
      10(-6), or 10(-5 m)) for 24 h. PNMC did not change basal levels of ACTH released
      from cultured anterior pituitary cells. However, PNMC significantly inhibited
      ACTH-stimulated production of corticosterone and progesterone from cultured
      adrenal cells. These results clearly show that PNMC has a direct effect on the
      adrenal gland to reduce corticosterone secretion, and the associated increase in
      plasma ACTH is probably due decreased negative feedback regulation by
      corticosterone.

PMID- 18057730
TI  - Effects of supplemented diacylglycerol rich in docosahexaenoic acid on serum
      triacylglycerol in a diet-induced hyperlipidemic model of rats are essentially
      equivalent to those of triacylglycerol rich in docosahexaenoic acid.
AB  - Effects of supplemented docosahexaenoic acid (DHA), given as diacylglycerol (DG)
      rich in DHA (DHA-DG), triacylglycerol (TG) rich in DHA (DHA-TG) or fish oil
      concentrate (DHA-70), on the serum concentration of TG and its bioavailability in
      the rats with diet-induced hyperlipidemia were studied. Hypertriglyceridemia was
      induced by feeding male Wistar rats a semi-purified diet that contained 5% corn
      oil and 50% sucrose by weight. In addition to the feeding of dietary corn oil,
      the rats received DHA intragastrically at a dose of 500 mg/kg body weight once a
      day for 28 d and the control rats were given olive oil. The serum concentration
      of TG in the rats that received DHA-DG was significantly lower than in the
      control rats. However, there were no significant differences in diet intake,
      energy intake, body weight gain, visceral fat mass or fecal excretion of total
      fatty acids among the four groups. The amounts of DHA excreted into the feces of
      the three groups of rats that received DHA were approximately 0.4% of the DHA
      administered. The extent of the decreases induced by DHA-DG in the serum level of
      TG was almost the same as those induced by DHA-TG and DHA-70. The administration
      of DHA, regardless of the differences in molecular structure, did not affect the
      hepatic contents of TG or phospholipid. The administration of DHA-DG considerably
      increased the proportions of DHA and eicosapentaenoic acid (EPA) while decreasing
      the proportion of arachidonic acid in hepatic lipids, and as a result in the
      lipids in serum and erythrocytes, to the same extents as did DHA-TG and DHA-70.
      These results suggest that the hypotriglyceridemic effects and bioavailability of
      DHA when supplemented in the form of DG are essentially equivalent to those of
      DHA-TG and DHA-70.

PMID- 18057731
TI  - Formation of spermidine or norspermidine from synthetic diacetylpolyamines by
      acetylpolyamine oxidase in cultured cells.
AB  - Prodrugs that can readily release polyamine into cells without the problem of
      generating cytotoxic compound by serum amine oxidase would be extremely useful
      for elucidation of polyamine function. As linear polyamines with acetamide groups
      on both sides are thought to be stable in the presence of serum amine oxidase and
      produce polyamines by the catalytic reaction of acetylpolyamine oxidase (PAO), a
      series of diacetyltetraamines, diacetylpentaamines and diacetylhexaamines was
      prepared as prodrugs and tested for substrate activity against PAO, partially
      purified from rat liver. Of the compounds, N(1),N(15)-diacetyl-1,15-diamino
      4,8,12-triazapentadecane (DA3333) and N(1),N(16)-diacetyl-1,16-diamino-4,8,13
      triazahexadecane (DA3343) were found to be stable in culture medium containing
      newborn bovine serum, and to produce reasonable amounts of norspermidine and
      spermidine, respectively. DA3333 and DA3343 were then applied to 1-aminooxy-3
      aminopropane (AOAP)-treated HTC cells with depleted putrescine and spermidine,
      and arrested growth. Cell growth recovered with DA3333 and DA3343, but growth
      rate was reduced in cells with added DA3333 compared with growth rates in cells
      with added DA3343 and control cells untreated with AOAP. Significant amounts of
      norspermidine and spermidine were found in cells with added DA3333 and DA3343,
      respectively. These results show the potential use of diacetylpolyamines in
      introducing polyamines into cells.

PMID- 18057732
TI  - Induction of apoptotic cell death by synthetic naringenin derivatives in human
      lung epithelial carcinoma A549 cells.
AB  - Although flavonoids, which are both qualitatively and quantitatively one of the
      largest groups of natural products, exhibit a variety of beneficial health
      effects, the exact molecular mechanism of the cellular activities is still not
      fully explained and there currently exists a lack of evidence for any
      relationship between the structure-activity relationship and apoptosis-inducing
      activity. In order to determine the importance of the OH group or substitution of
      the 5 or carbon-7 in the diphenylpropane skeleton of flavonoids, we originally
      synthesized several modified naringenin derivatives, including 7-O-benzyl
      naringenin (KUF-1) and 7-O-(MeO-L-Leu-D-Pro-carbonylmethyl) naringenin (KUF-7).
      Treatment with KUF-1 or KUF-7 resulted in significant apoptosis-inducing effects
      concomitant with chromatin condensation, caspase activation, and intracellular
      ROS production. Our data indicate that originally synthesized naringenin
      derivatives, KUF-1 and KUF-7 differentially regulate the apoptosis of A549 cells
      via intracellular ROS production coupled with the concomitant activation of the
      caspase cascade signaling pathway, thereby implying that hydroxylation or
      substitution at Carbon-7 is critical for the apoptosis-inducing activity of
      flavonoids.

PMID- 18057733
TI  - Effects of the serotonin and noradrenaline reuptake inhibitor (SNRI) milnacipran
      on marble burying behavior in mice.
AB  - The effects of milnacipran, a serotonin and noradrenaline reuptake inhibitor
      (SNRI) on the obsessive compulsive disorder (OCD) model, marble burying behavior,
      were investigated in mice. Milnacipran above the dosage of 10 mg/kg inhibited
      marble burying behavior significantly in mice as similar to fluvoxamine.
      Milnacipran inhibiting marble burying behavior did not affect locomotor activity.
      These results suggest that milnacipran can inhibit marble burying behavior and
      that milacipran may be useful for OCD therapy.

PMID- 18057734
TI  - Testosterone 5alpha-reductase inhibitory active constituents of Piper nigrum
      leaf.
AB  - Previously we reported that Piper nigrum leaf extract showed a potent stimulation
      effect on melanogenesis and that (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4
      desmethylenedioxycubebin (2) were isolated as active constituents. As a part of
      our continuous studies on Piper species for the development of cosmetic hair-care
      agents, testosterone 5alpha-reductase inhibitory activity of aqueous ethanolic
      extracts obtained from several different parts of six Piper species, namely Piper
      nigrum, P. methysticum, P. betle, P. kadsura, P. longum, and P. cubeba, were
      examined. Among them, the extracts of P. nigrum leaf, P. nigrum fruit and P.
      cubeba fruit showed potent inhibitory activity. Activity-guided fractionation of
      P. nigrum leaf extract led to the isolation of 1 and 2. Fruits of P. cubeba
      contain 1 as a major lignan, thus inhibitory activity of the fruit may be
      attributable to 1. As a result of further assay on other known constituents of
      the cited Piper species, it was found that piperine, a major alkaloid amide of P.
      nigrum fruit, showed potent inhibitory activity, thus a part of the inhibitory
      activity of P. nigrum fruit may depend on piperine. The 5alpha-reductase
      inhibitory activities of 1 and piperine were found for the first time. In
      addition, the P. nigrum leaf extract showed in vivo anti-androgenic activity
      using the hair regrowth assay in testosterone sensitive male C57Black/6CrSlc
      strain mice.

PMID- 18057735
TI  - In vivo evaluation of Kumazasa extract and chitosan films containing the extract
      against deep skin ulcer model in rats.
AB  - Kumazasa extract (KE) and its whole solid component (EXT)-containing chitosan
      films produced by drying in air and lyophilization, abbreviated to ND and FD
      films, respectively, were examined for efficacy and healing features using a deep
      skin ulcer model in rats. Their effects were compared with those of clinically
      available dosage forms, Beschitin W, Geben cream and U-PASTA. KE alone exhibited
      a better effect as compared with other preparations, and FD films also more
      effective than control in the early stage. Histological analysis showed that KE
      alone reduced necrosis rapidly and accelerated granulation. ND films delayed
      healing rate as compared with control. FD films showed histological features
      between control and KE alone, but tended to delay healing rate in the later
      period. Thus, reduction rate of wound area and histological features suggested
      that KE alone should be excellent for the promotion of wound healing. Although FD
      films were less effective than KE alone, they were superior as to usability such
      as changing the preparation.

PMID- 18057736
TI  - Sensitive extractive spectrophotometric methods for the determination of
      nortriptyline hydrochloride in pharmaceutical formulations.
AB  - Two simple, sensitive and rapid extractive spectrophotometric methods have been
      developed for the assay of the antidepressant drug nortriptyline (NOR)
      hydrochloride in pure form and in different dosage forms. The methods involve the
      formation of colored ion-pairs between the drug and the complex of niobium(V)
      thiocyanate (Nb-SCN) or iron(III)-thiocyanate (Fe-SCN) followed by their
      extraction with butanol or a mixture of butanol and chloroform and quantitative
      determination at 360 nm and 490 nm, using Nb-SCN and Fe-SCN, respectively. The
      experimental conditions were optimized to obtain the maximum colour intensity.
      The methods permit the determination of nortriptyline over a concentration range
      of 15-100 microg/ml and 5-24 microg/ml with the detection limit of 0.84 microg/ml
      and 0.32 microg/ml, using Nb-SCN and Fe-SCN, respectively. The proposed methods
      are applicable for the assay of the investigated drug in different dosage forms
      and the results are in good agreement with those obtained by the official and
      HPLC methods. No interference was observed from common excipients present in
      pharmaceutical formulations. The proposed procedures were applied to determine
      the amount of nortriptyline hydrochloride as active ingredient in the presence of
      its degradation product, dibenzosuberone. The extractive spectrophotometric
      methods can also be used to determine the amount of nortriptyline hydrochloride
      in tablets after its solid phase extraction (SPE).

PMID- 18057737
TI  - Spectrophotometric, spectrofluorometric and HPLC determination of desloratadine
      in dosage forms and human plasma.
AB  - Four sensitive, simple and specific methods were developed for the determination
      of desloratadine (DSL), a new antihistaminic drug in pharmaceutical preparations
      and biological fluids. Methods I and II are based on coupling DSL with 4-chloro-7
      nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer of pH 7.6 where a yellow
      colored reaction product was obtained and measured spectrophotometrically at 485
      nm (Method I). The same product could be measured spectrofluorometrically at 538
      nm after excitation at 480 nm (Method II). Methods III and IV, on the other hand,
      involved derivatization of DSL with 2,4-dinitrofluorobenzene (DNFB) in borate
      buffer of pH 9.0 producing a yellow colored product that absorbs maximally at 375
      nm (Method III). The same derivative was determined after separation adopting
      HPLC (Method IV). The separation was performed on a column packed with
      cyanopropyl bonded stationary phase equilibrated with a mobile phase composed of
      acetonitrile-water (60 : 40, v/v) at a flow rate of 1.0 ml min(-1) with UV
      detection at 375 nm. The calibration curves were linear over the concentration
      ranges of 0.5-6, 0.02-0.4, 1-10 and 1-30 microg ml(-1) for Methods I, II, III and
      IV, respectively. The lower detection limits (LOD) were 0.112, 0.004, 0.172 and
      0.290 microg ml(-1), respectively, for the four methods. The limits of
      quantification (LOQ) were 0.340, 0.012, 0.522 and 0.890 microg ml(-1) for Methods
      I, II, III and IV, respectively. The proposed methods were applied to the
      determination of desloratadine in its tablets and the results were in agreement
      with those obtained using a reference method. Furthermore, the
      spectrofluorometric method (Method II) was extended to the in-vitro determination
      of the drug in spiked human plasma, with a mean percentage recovery (n=4) of
      99.7+/-3.54. Interference arising from endogenous amino acids has been overcome
      using solid phase extraction. The proposed methods are highly specific for
      determination of DSL in the presence of the parent drug loratadine. A proposal
      for the reaction pathways is postulated.

PMID- 18057738
TI  - Marine diterpenoids with a briarane skeleton from the Okinawan soft coral
      Pachyclavularia violacea.
AB  - Five new briarane-type diterpenoids, pachyclavulides E (5), F (6), G (7), H (8)
      and I (9), were isolated from the Okinawan soft coral Pachyclavularia violacea.
      The structures of these compounds were elucidated based on the results of
      spectroscopic analysis. Compound 5 showed a weak growth-inhibitory activity in
      vitro toward cancer cells.

PMID- 18057739
TI  - On the chemical constituents of Dipsacus asper.
AB  - Bioassay-guided fractionation of 95% EtOH extract from the roots of Dipsacus
      asper lead to the isolation of some phenolic acids (caffeic acid, 2,6
      dihydroxycinnamic acid, vanillic acid, 2'-O-caffeoyl-D-glucopyranoside ester, and
      caffeoylquinic acid) as the major active components, and five new iridoid
      glucoside dimers (1-5) and one new iridoid glucoside monomer (6), other known
      iridoid glycosides loganin, cantleyoside, triplostoside A, lisianthioside, 6'-O
      beta-D-apiofuranosyl sweroside, as well as triterpenoids oleanic acid and
      akebiasaponin D. The structures of new compounds 1-6 were determined as
      dipsanosides C (1), D (2), E (3), F (4), G (5), and 3'-O-beta-D-glucopyranosyl
      sweroside (6) by spectroscopic, including 1D and 2D NMR techniques, and chemical
      methods.

PMID- 18057740
TI  - Novel water-soluble sedative-hypnotic agents: isoindolin-1-one derivatives.
AB  - We developed new intravenous sedative-hypnotic compounds with the isoindolin-1
      one skeleton focusing on the water-soluble property and in vivo safety. We
      synthesized approximately 170 derivatives and evaluated their hypnotic effects by
      intravenous administration of the compounds to mice. A series of the 2-phenyl-3
      [2-(4-methyl-1-piperazinyl)-2-oxoethyl]isoindolin-1-one analogs, 3(-), 5(-), 27(
      ), and 47(-) [JM-1232(-)], showed potent sedative-hypnotic activity with good
      water solubility and a wide safety margin. The hypnotic doses (HD50s) of these 4
      compounds when administered to mice were 2.35, 1.90, 2.17, and 3.12 mg/kg,
      respectively, and the lethal doses (LD50s) were 88.67, 64.69, >120, and >120
      mg/kg, respectively. The therapeutic indexes (LD50/HD50) were 37.73, 34.05,
      >55.30, and >38.46, respectively. Among these compound, 47(-) [JM-1232(-)] is
      being considered as the most potential candidate for clinical trials in humans.

PMID- 18057741
TI  - Solution equilibria between aluminum(III) ion and some fluoroquinolone family
      members. Spectroscopic and potentiometric study.
AB  - Complex formation between aluminum(III) ion and fluoroquinolone antibacterials
      either moxifloxacin (4th generation antibiotic) or fleroxacin (2nd generation
      antibiotic) were studied in aqueous solutions without and in the presence of
      sodium dodecylsulfate (SDS). The investigations were performed by glass electrode
      potentiometric (ionic medium: 0.1 mol/dm(3) LiCl, 298 K), UV spectrophotometric,
      multinuclear (1H and 13C) magnetic resonance and ESI-MS measurements. The
      experimental data were consistent with the formation of Al(HL)L2+, Al(HL)3+
      AlL2+, Al(OH)L+ and Al(OH)2L complexes in the pH interval ca. 3-8 and up to 5 : 1
      ligand to metal mole ratio with range of Al3+ concentrations between ca. 0.025 to
      1.0 mmol/dm3. The binary complex, AlL2+ is fairly stable (log beta(1,0,1) ca.
      11.0) and its stability increases in the presence of SDS. At higher concentration
      ratios of ligands to aluminum, up to 5 : 1, the complex Al(HL)L2+ is formed with
      rather high overall stability constant (log beta(1,1,2) ca. 24.0). The ESI-MS
      data generally, confirmed the derived model, and the formation of the complex
      with ligand to metal ratio 2 : 1. NMR measurements indicate that both ligands
      utilize 4-carbonyl and carboxyl oxygens as donor atoms. The presence of surface
      active substance, SDS, favors the formation of the complex in which the ligand is
      protonated, i.e. Al(HL) and its maximum formation is shifted toward milder acidic
      region (pH ca. 4). The aluminum-quinolone complexes may affect the bio
      distribution of both, quinolone and/or aluminum ion upon concomitant ingestion of
      aluminum-based antacids or phosphate binders and fluoroquinolones.

PMID- 18057742
TI  - Ascorbate analogs for use in medical imaging: synthesis and radical scavenging
      activity of 5-O-(4'-iodobenzyl)-L-ascorbic acid.
AB  - As part of our program to develop potential imaging agents for ascorbate
      bioactivity in the brain, 5-O-(4'-iodobenzyl)-L-ascorbic acid was prepared
      through a seven-step sequence which involved C5-O-alkylation with p-iodobenzyl
      bromide in the presence of Ag2O and CaSO4 as the key step, starting from L
      ascorbic acid. The scavenging activity of the p-iodobenzylated analog against 2,2
      diphenyl-1-picrylhyrazyl (DPPH) radical was almost the same as that of L-ascorbic
      acid itself.

PMID- 18057743
TI  - Synthesis and bioassay of amino-pyrazolone, amino-isoxazolone and amino
      pyrimidinone derivatives.
AB  - Novel amino-pyrazolone, amino-isoxazolone and amino-pyrimidinone derivatives were
      prepared from ethyl 4-phenylsulfonyl-2-(2'-phenylsulfonylethyl)-2-cyanobutyrate
      (1), ethyl 4-arylsulfonyl-3-aryl-2-cyanobutyrate (7) and ethyl 4
      arylmethylsulfonyl-3-aryl-2-cyanobutyrate (8). The lead molecules have been
      tested for their antimicrobial activity and antioxidant property.

PMID- 18057744
TI  - Enantioselective intramolecular aldol reaction mediated by a combination of L
      amino Acid and Bronsted Acid to construct a bicyclic enedione containing a 7
      membered ring.
AB  - The enantioselectivity of the intramolecular asymmetric aldol reaction of 1,3
      cycloheptanedione bearing a C-2 methyl substituent, mediated by a series of
      combinations of L-amino acid and Bronsted acid, was examined in detail.

PMID- 18057745
TI  - Improving the high variable bioavailability of griseofulvin by SEDDS.
AB  - To enhance the dissolution and oral absorption of poorly water-soluble
      griseofulvin (GF), self-emulsifying drug delivery system (SEDDS) composed of oil,
      surfactant and cosurfactant for oral administration of griseofulvin was
      formulated, and its physicochemical properties and pharmacokinetic parameters
      were evaluated. The solubility of griseofulvin was further improved by the
      addition of hydrochloric acid. Droplet size of griseofulvin emulsion was kept
      constant both in simulated gastric fluid without pepsin and simulated intestinal
      fluid throughout 12 weeks incubation period. Griseofulvin in the SEDDS rapidly
      dissolved in different dissolution media. This was not the case for the
      commercial GRIS-PEG tablets. In different fed diet groups, AUC 0-->24 h, Cp max,
      and T max of griseofulvin after oral administration of SEDDS in rats were
      comparable to those after oral dose of GRIS-PEG tablet. Although, in fed lipidic
      diet group, the mean AUC and Cp max after oral administration of GRIS-PEG in rats
      were 1.28 and 1.15 fold higher, respectively, compared with those of SEDDS, these
      have not shown to be significantly different. These results demonstrate that the
      SEDDS of griseofulvin composed of Capmul GMO-50, Poloxamer and Myvacet 9-45
      greatly enhanced the dissolution of griseofulvin (without ultramicronisation).
      However, food intake effect on the bioavailability of griseofulvin has remained.
      Thus, this system may provide a useful dosage form for oral water-insoluble drugs
      which have problems in their dissolution.

PMID- 18057746
TI  - Glycolipids from the formosan soft coral Lobophytum crassum.
AB  - Three glycolipids (1--3), possessing a sugar moiety at C-2 of glycerol ether,
      have been isolated from the Formosan soft coral Lobophytum crassum. Their
      structures were elucidated by spectroscopic methods, particularly in 1D- and 2D
      NMR experiments. The absolute configurations on the sugar portion and lipid
      aglycon of 1--3 were determined by methanolysis, chemical transformation and the
      application of Mosher's method on 1 and 3. Compounds 1--3 exhibited weak
      cytotoxic activities.

PMID- 18057748
TI  - Metachromins R--T, new sesquiterpenoids from marine sponge Spongia sp.
AB  - Three new sesquiterpenoids, metachromins R--T (1--3), have been isolated from an
      Okinawan marine sponge Spongia sp. The structures and stereochemistry of 1--3
      were elucidated on the basis of the spectroscopic data. Metachromins S (2) and T
      (3) showed modest cytotoxicity.

PMID- 18057747
TI  - Semi-synthesis of polymyxin B (2-10) and colistin (2-10) analogs employing the
      Trichloroethoxycarbonyl (Troc) group for side chain protection of alpha,gamma
      diaminobutyric acid residues.
AB  - Improved strategies for the chemical conversion of natural polymyxin B and
      colistin to their N-terminal analogs are reported. First, the protection of the
      side chains of five L-alpha,gamma-diaminobutyric acid (Dab) residues in natural
      polymyxin B and colistin was achieved with trichloroethoxycarbonyl (Troc), then
      the resulting pentakis(N gamma-Troc)-polymyxin B and pentakis(N gamma)Troc)
      colistin were treated with trifluoroacetic acid (TFA) : methanesulfonic acid
      (MSA) : dimethylformamide (DMF) : H2O (10 : 30 : 55 : 5) at 40 degrees C in order
      to remove N alpha-alkanoyl-Dab(Troc)-OH selectively. The new key compounds,
      tetrakis(N gamma-Troc)-polymyxin B (2-10) and tetrakis(N gamma-Troc)-colistin (2
      10), were obtained in 19% and 15% yields, respectively, which is higher than
      previous reports using trifluoroacetyl (Tfa) for tetrakis(N gamma-Tfa)-polymyxin
      B (2-10) and tetrakis(N gamma-Tfa)-colistin (2-10), respectively. Acylation of
      tetrakis(N gamma-Troc)-polymyxin B (2-10) and tetrakis(N gamma-Troc)-colistin (2
      10) with various hydrophobic acids bearing aliphatic or aromatic ring structures,
      followed by the deprotection of Troc by Zn in AcOH, produced polymyxin B (2-10)
      and colistin (2-10) analogs which were used for structure-activity relationship
      studies. It was found that cyclohexylbutanoyl-, 4-biphenylacetyl-, and 1
      adamantaneacetyl-polymyxin B (2-10) showed potent antimicrobial activity equal to
      that of polymyxin B against three Gram-negative bacterial strains. The
      lipopolysacharide (LPS) binding activity of cyclohexylbutanoyl-, 4-biphenylacetyl
      , and cyclododecanecarbonyl-polymyxin B (2-10) increased greatly in comparison
      with that of polymyxin B (2-10). The various N alpha-acylated polymyxin B (2-10)
      analogs showed slightly higher antimicrobial and LPS binding activities than the
      corresponding N alpha-acylated colistin (2-10) analogs.

PMID- 18057749
TI  - Facile synthesis of trisaccharide moiety corresponding to antitumor activity in
      triterpenoid saponins isolated from Pullsatilla roots.
AB  - A trisaccharide found in triterpenoid saponins isolated from Pullsatilla roots
      appears as an important promoiety for the enhancement of anticancer activity of
      their aglycones. Thus a facile synthetic method for a trisaccharide moiety, allyl
      2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl-(1-->2)-[2,3,4,6-tetra-O-benzoyl-beta
      D-glucopyranosyl-(1-->4)]-3-O-benzoyl-beta-L-arabinopyranoside (3), has been
      firstly developed through the regio- and stereoselective glycosylations from
      arabinose in total 16% yield via route 2 (eight steps). In this synthetic
      procedure, the protection of anomeric -OH of L-arabinose with equatorially
      oriented allyl group unlike with the axial 4-methoxybenzyl protecting group well
      promoted glycosyl bond formation between alpha-L-rhamnopyranosyl
      trichloroacetimidate and 2-OH of arabinose. As expected, the synthesized
      trisaccharide moiety 3 has no cytotoxicity (ED50: >100 microM) against three
      human cancer cell lines (A-549, SK-OV-3, and SK-MEL-2), respectively.

PMID- 18057750
TI  - Synthesis and HIV-1 integrase inhibition of novel bis- or tetra-coumarin
      analogues.
AB  - Present studies were undertaken on the preparation of synthetic analogues of bis-
      or tetra-coumarins and their activity against HIV-1 integrase (HIV-1 IN). Among
      these coumarin analogues, compounds 14, 16 and 18 were found to be potent
      molecules against HIV-1 IN at IC50 values of 0.96, 0.58, and 0.49 microM,
      respectively. The results provided a tool for guiding the further design of more
      potent antiviral agents and for predicting the affinity of related compounds.

PMID- 18057751
TI  - Abietane lactones and iridoids from Goldfussia yunnanensis.
AB  - Two new abietane diterpene lactones (1--2), three new abietane diterpene lactone
      glycosides (3--5) and a new iridoid glycoside (6), together with five known
      compounds, were isolated from the aerial parts of Goldfussia yunnanensis. The new
      compounds were determined to be 18-hydroxyhelioscopinolide A (1), 18
      oxohelioscopinolide A (2), 18-hydroxy-3-O-beta-D-glucopyranosylhelioscopinolide A
      (3), 3-O-beta-D-glucopyranosylhelioscopinolide A (4), 3-O-beta-D
      galactopyranosylhelioscopinolide A (5), and 6-O-trans-cinnamoyl E-harpagoside (6)
      on the basis of spectral data and chemical evidence.

PMID- 18057752
TI  - Cytotoxic fatty acid from Pleurocybella porrigens.
AB  - The new conjugated ketonic fatty acid, porrigenic acid (1), was isolated as a
      cytotoxic constituent of Pleurocybella porrigens. The structure of 1 was
      elucidated using spectroscopic methods including 1D and 2D NMR and MS. The
      absolute stereochemistry of 1 was determined by application of the exciton
      chirality method. Compound 1 exhibited cytotoxic activity against myeloma THP-1
      cells, but did not show any significant toxicity against B16F1 melanoma. This is
      the first report of the isolation and structural elucidation of the new cytotoxic
      constituent porrigenic acid (1) from the edible mushroom P. porrigens.

PMID- 18057753
TI  - Structural development of liver X receptor (LXR) antagonists derived from
      thalidomide-related glucosidase inhibitors.
AB  - Following our previous discovery of LXR antagonistic activity of 2'-substituted
      phenylphthalimides derived from thalidomide-related glucosidase inhibitors,
      structure-activity studies and further structural development led to 5-chloro-N
      2'-n-pentylphenyl-1,3-dithiophthalimide (5CPPSS-50), with IC50 values of about 10
      and 13 microM for LXRalpha and LXRbeta, respectively.

PMID- 18057754
TI  - Antifungal activity of some diaryl ethers.
AB  - Several diaryl ethers were synthesized and tested in vitro against seven
      phytopathogenic fungi, namely Fusarium graminearum, Alternaria alternate,
      Helminthosporium sorokinianum, Pyricularia oryzae, Fusarium oxysporum f. sp.
      vasinfectum, Fusarium oxysporum f. sp. cucumarinum and Alternaria brassicae.
      Compared to a commercial agricultural fungicide, hymexazol, especially compounds
      a, b, e, g and k were found to be more effective at 50 mug/ml against F.
      graminearum, F. oxysporum f. sp. vasinfectum and F. oxysporum f. sp. cucumarinum.
      Meantime, some structure-activity relationships were also observed.

PMID- 18057755
TI  - A study of the calcium complex of a glucosylceramide, soya-cerebroside II.
AB  - In order to study calcium ion complex of soya-cerebroside II (1), an ionophoretic
      glucosylceramide isolated from soybean, C8-cerebroside (3) and 3,3'',6''-trideoxy
      C8-cerebroside (4) are designed and synthesized. On the basis of extensive 1H-NMR
      studies in the presence of Ca2+ and a continuous variation method via (1)H-NMR,
      soya-cerebroside II is suggested to form a calcium complex with 1/Ca2+ ratio of 1
      : 1. Soya-cerebroside II serves as a tridentate chelating ligand for Ca2+; the
      amide carbonyl, C2'-hydroxy, and C2''-hydroxy oxygens are responsible for the
      Ca2+ binding. Soya-cerebroside II is structurally analogous to a neural
      glucosylceramide. Thus, the accumulated neural glucosylceramide inside of
      endoplasmic reticulum (ER) membrane may serve as an endogenous Ca2+-binding and 
      transport molecule (ionophore) that result in mobilization of Ca2+ from
      intracellular calcium stores.

PMID- 18057756
TI  - Synthesis of 2,2'-Bis(3,6,9-triazanonyl)-4,4'-bithiazole and related compounds as
      new DNA cleavage agents.
AB  - Two new bithiazole derivatives, 2,2'-bis(3,6,9-triazanonyl)- and 2,2'-bis(3,7,11
      triazaundecyl)-4,4'-bithiazoles (3a, b), were readily synthesized in six steps
      using the corresponding dialkylenetriamine as starting materials. Under
      physiological conditions, 5.0 microM 3a exhibited significant DNA cleavage
      activity in the presence of Co(II), whereas even at 50 micriM, 3b exhibited no
      DNA cleavage activity. Furthermore, it was demonstrated that 3a forms a 1 : 2
      complex with Co(II) ions, whereas 3b does not. These conclusions were based on
      measurements of stoichiometries of the bithiazole-cobalt complexes obtained by
      the Job continuous variation method. In contrast, 3a, which contains
      diethylenetriamine moieties, showed decreased affinity for Calf Thymus (CT) DNA
      compared with that of 3b, which contains dipropylenetriamine moieties. These
      findings indicate that the structure of the two aminoalkyl side chains attached
      at the 2- and 2'-positions of the 4,4'-bithiazole ring significantly influence
      the formation of cobalt complexes, and affects the compound's ability to cleave
      DNA as well as its affinity for double-stranded DNA.

PMID- 18057757
TI  - Structures of epicatechin gallate trimer and tetramer produced by enzymatic
      oxidation.
AB  - During black tea production, catechins and their galloyl esters are enzymatically
      oxidized to generate a complex mixture of black tea polyphenols. The role of
      galloyl ester groups in this process has yet to be determined. Enzymatic
      oxidation of epicatechin 3-O-gallate (1) yielded two new oxidation products,
      theaflavate C and bistheaflavate A, along with theaflavate A (2), a known dimer
      of 1 generated by coupling of the B-ring with the galloyl group. Theaflavate C is
      a trimer of 1 and possesses two benzotropolone moieties generated by the
      oxidative coupling of the galloyl groups with the catechol B-rings.
      Bistheaflavate A was found to be a tetramer produced by intermolecular coupling
      of two benzotropolone moieties of 2. From the structures of the products, it was
      deduced that oxidative coupling of galloyl groups resulted in extension of the
      molecular size of the products in catechin oxidation.

PMID- 18057758
TI  - Effects of magnesium salts and amines on the stereoselectivity in the imine aldol
      reaction.
AB  - In the imine aldol reactions of 1 with aromatic aldehydes using magnesium salts
      in the presence of amines, the threo/erythro ratios of products increased in the
      order Mg(ClO4)2>MgI2>MgBr2>MgCl2>Mg(OTf)2 and N,N,N',N'
      tetramethylethylenediamine (TMEDA)>Et3N. This increase in the threo/erythro
      ratios of products was estimated to be caused by a retro-imine aldol reaction
      under thermodynamic control.

PMID- 18057759
TI  - Physical diagnosis of chronic obstructive pulmonary disease.
AB  - Among the various diagnostic strategies of chronic obstructive pulmonary disease
      (COPD), physical diagnosis is the quickest and requires no extra cost. Rapid
      physical diagnosis of COPD in primary care practice can lead to earlier actions
      of preventive measures and counseling for patients. Further, rapid physical
      diagnosis of COPD in an emergency department is also crucial for timely use of
      potentially lifesaving therapy specific for COPD patients. In this review, we
      will present a broad scope of physical findings for rapid physical diagnosis of
      COPD.

PMID- 18057760
TI  - Effect of combination therapy of a rapid-acting insulin secretagogue (glinide)
      with premixed insulin in type 2 diabetes mellitus.
AB  - AIM: The effect of rapid-acting insulin secretagogues (glinides) on glycemic
      control when included with insulin therapy for type 2 diabetes remains uncertain.
      To examine this, we added glinide once a day to twice daily injections of
      premixed insulin. RESEARCH DESIGN AND METHODS: Seventy-four type 2 diabetic
      patients, taking twice daily injections of premixed insulin and whose diabetic
      control was stable, were registered at 6 independent institutions. After a 3
      month observation period, 60 patients were administered 10 mg mitiglinide or 90
      mg nateglinide at lunchtime without changing their insulin regimen. After 12
      weeks, administration of glinide was discontinued and observation was continued.
      HbA1c levels were measured at the start of glinide administration, after 12 weeks
      of glinide , and at 12 weeks after discontinuation. RESULTS: HbA1c improved from
      7.72+/-0.66% to 7.55+/-0.71% (p <0.01) at Week 12 of glinide administration.
      Twelve weeks after discontinuation, HbA1c returned to the baseline level (7.72+/
      0.81%). CONCLUSION: This study indicates that the addition of glinide once a day
      at lunchtime to twice daily injections of premixed insulin is effective for the
      treatment of type 2 diabetes.

PMID- 18057761
TI  - Influence of motorization and supermarket-proliferation on the prevalence of type
      2 diabetes in the inhabitants of a small town on Okinawa, Japan.
AB  - BACKGROUND: Motorization and supermarket-proliferation affect lifestyles. About
      15 years ago, Okinawans went to several shops on foot, but now they go to
      supermarkets by car. The influences of these changes on the prevalence of
      diabetes are uncertain. OBJECTIVE AND MEASUREMENTS: The influence of motorization
      and supermarket-proliferation on the prevalence of diabetes was studied in the
      inhabitants of a town on Okinawa, Japan. Measurements were composed of
      anthropometry and blood chemistry. Participants were asked where they buy food
      and daily necessities (several shops or a supermarket) and how they get there (by
      car or on foot). DESIGN: Serial cross-sectional. PARTICIPANTS: Inhabitants of the
      island of Okinawa were studied. RESULTS: In 1991, 24% went to several shops and
      20% to a supermarket. However, in 2004, only 3.1% went to several shops and 83%
      to a supermarket. In 1991, 55% went to shopping places on foot and 38% by car.
      However, in 2004, only 14% went on foot and 76% by car. The prevalence of
      diabetes in Okinawa increased from 4.7% in 1991 to 8.4% in 2004. The prevalence
      of diabetes correlated positively with the percent of inhabitants going to
      supermarkets, and those going there by car. In 1991, the prevalence of type 2
      diabetes was 4.7% in men and 4.6% in women; no difference was noted between men
      and women. In 2004, the prevalence of type 2 diabetes increased to 9.2% in men
      and to 7.5% in women. The increase in the prevalence of type 2 diabetes from 1991
      to 2004 was higher in men than in women. CONCLUSIONS: About 15 years ago,
      Okinawans went to shops on foot, but now they go to supermarkets by car. The
      prevalence of diabetes is increasing. Motorization and supermarket-proliferation
      are associated with the increases of the prevalence of diabetes. The increase in
      diabetes prevalence was higher in men than in women.

PMID- 18057762
TI  - Elevation of serum thioredoxin in patients with gefitinib-induced interstitial
      lung disease.
AB  - OBJECTIVE: Interstitial lung disease (ILD) is a severe adverse event of gefitinib
      therapy. However, the mechanism still remains unclear. The objective of this
      study was to examine whether or not oxidative stress, one of the common factors
      in drug-associated ILD, is involved in the pathogenesis of gefitinib-induced ILD.
      PATIENTS AND METHODS: Using an enzyme-linked immunosorbent assay (ELISA), we
      measured the concentration of serum thioredoxin (Trx), a redox-active protein
      with antioxidative effects, in 44 patients treated with gefitinib, including
      three patients who had ILD. RESULTS: In patients who had gefitinib-induced ILD,
      serum Trx levels were significantly elevated. They decreased after cessation of
      gefitinib therapy accompanying clinical improvement of ILD. CONCLUSION: It was
      suggested that oxidative stress may be involved as a part of mechanisms causing
      or worsening gefitinib-induced ILD.

PMID- 18057763
TI  - Early stage of colonic adenocarcinoma associated with traditional serrated
      adenoma.
AB  - We describe a 68-year-old woman diagnosed as having a colonic adenocarcinoma
      associated with traditional serrated adenoma (SA) with submucosal invasion of the
      sigmoid colon. Colonoscopy revealed a 0-IIa+IIc colon cancer with a SA component,
      about 12 mm in diameter, in the sigmoid colon. She underwent laparoscopy-assisted
      resection of the sigmoid colon. In the resected specimen, colon cancer with mucin
      pools was adjacent to the SA. Cases of colonic adenocarcinoma associated with
      traditional SA with submucosal invasion are relatively rare. This case suggests
      that SA may play a role in the development of colorectal cancer.

PMID- 18057764
TI  - Thyrotoxicosis with coronary spasm that required coronary artery bypass surgery.
AB  - We describe a 47-year-old woman with severe coronary vasospasm induced by
      hyperthyroidism. The patient complained of anginal chest pain without specific
      characteristics of thyrotoxicosis. Coronary arteriography was performed and
      revealed 90% stenosis of both the left and right coronary os. She was treated
      with emergent coronary artery bypass graft surgery. Postoperatively, she
      exhibited a comatose mentality. Severe thyrotoxicosis was indicated on thyroid
      function tests and thyrotoxic storm was diagnosed. Nineteen days after the
      surgery and following the initiation of propylthiouracil treatment, coronary
      arteriography revealed entirely normal coronary arteries.

PMID- 18057765
TI  - Hypereosinophilic syndrome accompanied by Buerger's disease-like femoral arterial
      occlusions.
AB  - A case of hypereosinophilic syndrome (HES) with a rare complication of Buerger's
      disease-like large arterial occlusion (AO) was successfully treated with emergent
      percutaneous transluminal angioplasty and anticoagulants plus corticosteroid. By
      reviewing 15 reported cases of HES with AO including the present case, we found
      man predominance but no other consistent characteristics in HES with AO, such as
      age, smoking history, eosinophil counts or previous treatments, thus, predicting
      AO in HES patients appears to be difficult. Vessel intervention should be
      considered as a treatment option, since treatment delay in some patients has
      resulted in the amputation of extremities.

PMID- 18057766
TI  - Long-term sustained mixed chimerism after allogeneic stem cell transplantation in
      a patient with severe aplastic anemia.
AB  - Mixed chimerism in a post-transplant patient with severe aplastic anemia (SAA) is
      generally considered to be a status preceding donor-cell rejection and bone
      marrow failure. Here, we report on a rare, prolonged mixed chimerism in a patient
      with SAA who showed a full recovery in hematological and immunological status
      after transplantation. The analysis in this patient showed about 20% and 80%
      recipient-type cells of total blood cells and T cells, respectively, at two years
      post-transplantation, and 14% and 25% of total blood cells and T cells,
      respectively, at four years post-transplantation. This report describes the most
      comprehensive case study known to date.

PMID- 18057767
TI  - Inflammatory myopathy with anti-Golgi antibody and anti-SS-A/Ro antibody.
AB  - We report a 74-year-old woman with anit-Golgi antibody and anti-SS-A/Ro antibody
      who contracted inflammatory myopahy presenting 'ALS-like' symptoms. We identified
      anti-Golgi antibody directly using confocal microscopy and successfully treated
      her with steroid. This report suggests that there is a new categorized subgroup
      of inflammatory myopathy with these specific antibodies and the pattern of
      autoantibody in these patients indicates the specific clinical course and
      treatment strategy.

PMID- 18057768
TI  - Mechanism of formation of the orange-colored sputum in pneumonia caused by
      Legionella pneumophila.
AB  - It has been said that the color of sputum from patients with Legionella
      pneumophila pneumonia is orange. However, why the color is orange has not been
      clarified. First, orange-colored sputum obtained from a patient with L.
      pneumophila pneumonia is presented. Then, the formation of an orange-colored
      pigment in a culture medium (without charcoal) after the growth of L. pneumophila
      is demonstrated.

PMID- 18057769
TI  - Combined and staged endovascular recanalization of cervical and intracranial
      arteries in hyperacute ischemic stroke.

PMID- 18057770
TI  - Gabapentin for painful legs and moving toes syndrome.

PMID- 18057771
TI  - Pulmonary sarcoidosis with massive parenchymal masses.

PMID- 18057772
TI  - Irreversible imatinib-induced pneumonitis following long-term imatinib
      administration.

PMID- 18057773
TI  - Splenic abscess caused by actinomycosis.

PMID- 18057774
TI  - 2,5-Dimethoxy-4-iodoamphetamine (DOI) inhibits Delta9-tetrahydrocannabinol
      induced catalepsy-like immobilization in mice.
AB  - The effect of the serotonin 5-HT(2A/2C)-receptor agonist 2,5-dimethoxy-4
      iodoamphetamine (DOI) on Delta(9)-tetrahydrocannabinol (THC)-induced catalepsy
      like immobilization was studied in mice. DOI (0.3 and 1 mg/kg, i.p.)
      significantly inhibited the catalepsy-like immobilization induced by THC (10
      mg/kg, i.p.). In contrast, the selective 5-HT(2C)-receptor agonist 8,9-dichloro
      2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one (WAY 161503) had no
      effect on this catalepsy-like immobilization. Moreover, the 5-HT(2A)-receptor
      antagonist ketanserin (0.3 mg/kg, i.p.) reversed the inhibition of THC-induced
      catalepsy-like immobilization caused by DOI (1 mg/kg), whereas the selective 5
      HT(2C)-receptor antagonist 6-chloro-2,3-dihydro-5-methyl-N-[6-(2-methyl-3
      pyridinyl)oxyl]-3-pyridinyl]-1H-indole-1-carboxyamide (SB 242084) did not affect
      this inhibitory effect of DOI. On the other hand, ketanserin (0.3 and 1 mg/kg,
      i.p.) enhanced the catalepsy-like immobilization induced by THC (6 mg/kg, i.p.).
      Thus, on the basis of these results, it appears that 5-HT(2A)-receptor mechanisms
      might be responsible for the inhibitory effect of DOI on THC-induced catalepsy
      like immobilization.

PMID- 18057775
TI  - Shengmai-san enhances antioxidant potential in C2C12 myoblasts through the
      induction of intracellular glutathione peroxidase.
AB  - Cellular and tissue injury associated with reactive oxygen species (ROS) has been
      reported in many kinds of disorders. While the antioxidant enzymes play critical
      roles in inhibiting the ROS-mediated injury, glutathione peroxidase (GPx) is
      scavenging hydroperoxides including H(2)O(2). We previously reported that
      Shengmai-san (SMS), a traditional Chinese medicine, prevented
      ischemia/reperfusion injury of the brain and other organs in rats. To clarify the
      effect of SMS on intracellular responses of muscle cells against oxidative
      stress, C2C12 myoblasts were subjected to H(2)O(2) abuse. SMS pre-incubation
      prevented the decreasing cell viability after H(2)O(2) treatment. The
      accumulations of cellular protein carbonyl associated with apoptotic cell death
      were also inhibited by the SMS pre-incubation prior to oxidative damage
      induction. At the same time, enhanced activity, protein, and mRNA expression
      levels of GPx were observed in cells pre-incubated with SMS prior to H(2)O(2)
      abuse. Moreover, intracellular GSH was subsequently decreased after H(2)O(2)
      treatment. These findings suggest that SMS improved the antioxidant capacity
      against acute oxidative stress through the constitutive enhancement of GPx
      expression in C2C12 myoblasts. Because of its antioxidative property, SMS might
      be useful not only for the oxidative damage associated diseases but also for the
      transplantation of myoblasts into muscular dystrophy patients.

PMID- 18057776
TI  - Pravastatin induces rat aortic endothelial cell proliferation and migration via
      activation of PI3K/Akt/mTOR/p70 S6 kinase signaling.
AB  - The HMG-CoA reductase inhibitors (statins) have been shown to exert several
      vascular protective effects that are not related to changes in cholesterol
      profile, and these effects of statins are partly caused by the activation of
      angiogenesis. Endothelial cell (EC) proliferation and migration are crucial
      events for angiogenesis and statins are known to enhance these events. However,
      the molecular mechanism by which statins promote EC proliferation and migration
      is not fully understood. In this study, we show Akt and its downstream target
      mammalian target of rapamycin (mTOR) play an important role in pravastatin
      induced EC proliferation and migration. We found that pravastatin significantly
      enhanced the proliferation and migration of rat aortic endothelial cells (rAECs).
      The addition of pravastatin to rAECs resulted in rapid phosphorylation of Akt and
      p70 S6 kinase (p70S6K). LY294002, a specific inhibitor of phosphatidylinositol 3
      kinase (PI3K), blocked both Akt and p70S6K phosphorylation, whereas rapamycin, a
      specific inhibitor of mTOR, suppressed only p70S6K phosphorylation induced by
      pravastatin. Furthermore, both LY294002 and rapamycin inhibited pravastatin
      induced rAEC proliferation and migration. Taken together, our findings indicate
      that pravastatin activates PI3K/Akt/mTOR /p70S6K signaling in this sequential
      manner and this pathway contributes to pravastatin-induced rAEC proliferation and
      migration.

PMID- 18057777
TI  - Complicated interaction between psychostimulants and morphine in expression of
      phenotype of behavior in the dopaminergic system of BALB/c mice.
AB  - It is believed that BALB/c mice appear to be less sensitive to the locomotor
      effects of abused drugs compared to other strains, and several behaviors induced
      by abused drugs depend on genetic factors. The present study was designed to
      investigate the effects of the interaction between psychostimulants and morphine
      on behavior in BALB/c mice. Morphine and cocaine induced hyperlocomotion and
      hypolocomotion, respectively, while methamphetamine did not affect locomotor
      activity and high doses of methamphetamine significantly increased self-injurious
      behavior. Cocaine or methamphetamine increased the effects of morphine on
      locomotor behavior. Haloperidol (a dopamine-receptor antagonist) attenuated the
      hyperlocomotion induced by the combination of cocaine or methamphetamine plus
      morphine. These results indicate that the synergistic effects of methamphetamine
      or cocaine and morphine on locomotor activity are mediated through enhancement of
      the dopaminergic system and that combinations of psychostimulants and morphine
      enhance the locomotor activity in BALB/c mice. On the other hand, morphine
      completely attenuated methamphetamine-induced self-injurious behavior.
      Furthermore, a low dose (0.01 mg/kg) of haloperidol significantly increased the
      effects of methamphetamine and morphine on the locomotor activity.
      Hyperlocomotion induced by psychostimulants is mediated by the mesolimbic
      dopaminergic system, whereas stereotyped behaviors is mediated by the
      nigrostriatal dopaminergic system. Our findings suggest that balances of the
      activation of dopaminergic neurons (between mesolimbic and nigrostriatal systems)
      may play an important role to engender corresponding behavioral outcomes in
      BALB/c mice.

PMID- 18057778
TI  - [Highly selective recognition and detection of biomolecules using designed
      functional molecule].

PMID- 18057779
TI  - [Specific recognition and detection of phosphorylated proteins using
      characteristics of metal ion].
AB  - Protein phosphorylation is one of the most important post-translational
      modifications. Organisms utilize this reversible reaction of proteins to control
      many cellular activities, including signal transduction, apoptosis, gene
      expression, cell cycle progression, cytoskeletal regulation, and energy
      metabolism. Abnormal protein phosphorylation is deeply related to carcinogenesis
      and neuropathogenesis. Methods for monitoring the phosphorylation status of
      proteins are, thus, very important with respect to the evaluation of diverse
      biological and pathological processes. Recently, we reported that a dinuclear
      metal complex of 1,3-bis[bis(pyridin-2-ylmethyl)-amino]propan-2-olato acts as a
      novel phosphate-binding tag molecule, Phos-tag, in an aqueous solution under
      physiological conditions. The Phos-tag has a vacancy on two metal ions that is
      suitable for the access of a phosphomonoester dianion (R-OPO(2)3*) as a bridging
      ligand. The resulting 1:1 phosphate-binding complex, R-OPO(2)3*-(Phos-tag)3+, has
      a total charge of +1. A dinuclear zinc(II) complex (Zn2+-Phos-tag) strongly binds
      to phenyl phosphate dianion (K(d)=2.5 x 10(-8) M) at a neutral pH. The anion
      selectivity indexes against SO(2)4*, CH3COO*, Cl-, and bisphenyl phosphate
      monoanion at 25 degrees C are 5.2 x 10(3), 1.6 x 10(4), 8.0 x 10(5), and>2 x
      10(6), respectively. A manganese(II) homologue (Mn2+-Phos-tag) can also capture
      the R-OPO(2)3* anion, such as phosphoserine, phosphotyrosine, and
      phosphohistidine, at an alkaline pH. By utilizing the Phos-tag molecule and its
      derivatives, we developed convenient and reliable methods for the detection of
      phosphorylated proteins. We believe that our Phos-tag technology will result in
      great progress in phosphoproteomics.

PMID- 18057780
TI  - [Selective recognition and detection of biomacromolecules utilizing chemical
      property of amino Acid or Peptide].
AB  - Recently, the fluorometric detection of biomacromolecules has attracted much
      attention. In this paper, we report the development of two new techniques
      utilizing the chemical properties of amino acids or peptides: 1) a fluorescence
      assay for serine/threonine kinase activity; and 2) "turn-on" fluorescent probes
      for protein labeling, which could be useful for bioimaging. To develop the novel
      kinase assay, we utilized the chemical reactivity of phosphorylated serine or
      threonine. Phosphorylated peptide on resin was successfully labeled fluorescently
      via base-mediated beta-elimination, followed by Michael addition with novel
      coumarin derivatives. Protein kinase A and casein kinase I activities were
      detectable with our method. Also, this method was confirmed to be applicable for
      kinase inhibitor screening. For the development of the novel protein labeling
      technique, the selective interaction between "His-tag (His(6))" and "metal ion
      nitrilotriacetic acid (NTA) complex" was utilized. This interaction is useful for
      protein purification and immobilization. We designed fluorescent probes composed
      of a fluorophore and Ni2+ or Co2+-NTA complex. These probes were found to be
      weakly fluorescent as expected. When His-tag peptide was added, these probes
      became brightly fluorescent. On the other hand, these probes remained non
      fluorescent with the addition of angiotensin I (H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
      His-Leu-OH). These probes will be powerful tools for the bioimaging of target
      proteins.

PMID- 18057781
TI  - [Role of isomerized protein repair enzyme, PIMT, in cellular functions].
AB  - Proteins are subject to various types of spontaneous modifications that can
      disrupt their structures with sometimes adverse affects on biological activity.
      The formation of L-isoaspartyl (or D-aspartyl) residues, through either the
      deamidation of asparagine or dehydration of aspartate, is one of the most
      frequent types of deterioration occurring under physiological conditions. Protein
      L-isoaspartate/D-aspartate o-methyltransferase (PIMT) is a conserved and
      ubiquitous enzyme that participates in the repair of various isomerized proteins.
      PIMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine onto
      the alpha-carboxyl group of an L-isoaspartyl (or the beta-carboxyl group of an D
      aspartyl) residue, which initiates the conversion of this residue to an L
      aspartyl residue. PIMT-deficient mice have been shown to die at a mean age of 42
      days from progressive epileptic seizures with grand mal and myoclonus. Although
      PIMT-deficiency clearly leads to the accumulation of isomerized proteins, it is
      currently unclear how this causes progressive epilepsy in PIMT-deficient mice. As
      a first step towards understanding this, we developed a new assay to measure PIMT
      activity in cell lysates. Additionally, we isolated PIMT knockdown cells from
      HEK293 cells that were stably transfected with a PIMT small interfering RNA
      expression vector. PIMT activities were significantly decreased in the PIMT
      knockdown cells, and analysis of the transfectants revealed that MEK and ERK were
      hyperactivated after cell stimulation with epidermal growth factor (EGF). These
      results indicate that the ability to repair L-isoaspartyl-(or D-aspartyl-)
      containing proteins is important for the maintenance of normal MEK-ERK signaling.

PMID- 18057782
TI  - [Development of bifunctional radiopharmaceuticals for targeted imaging and
      therapy].
AB  - In vivo radiopharmaceuticals have two different uses - for nuclear diagnostic
      imaging and for internal radiation therapy. For nuclear diagnostic imaging, it is
      necessary to make the difference of radioactivity levels between in the target
      regions and in the other regions at an early time after administration. For
      internal radiation therapy, a more selective accumulation of the radioactivity to
      the target regions is required to minimize an adverse effect. In order to achieve
      the highly selective accumulation of in vivo radiopharmaceuticals, it is
      necessary to find an appropriate target molecule in the first place and design a
      compound which can recognize the target molecule and stably label it with
      radionuclide. There are several proposed approaches to chemical design for this
      purpose. However, even with the specific recognition and stable radiolabel,
      targeted imaging and therapy are not necessarily achieved. We have been
      developing in vivo radiopharmaceuticals based on a chemical design called
      "bifunctional radiopharmaceutical." Bifunctional radiopharmaceuticals have the
      recognition site of the target molecule and binding site for the radionuclide
      independently in one molecule. This review summarizes our examples of chemical
      design of in vivo radiopharmaceuticals to achieve the targeted imaging and
      therapy.

PMID- 18057783
TI  - [Molecular toxicology lead by young scientists: Chemical toxicology and
      transcriptional factors].

PMID- 18057784
TI  - [Chemical biology of 1,2-naphthoquinone, a novel air pollutant that affects
      signal transduction pathways].
AB  - Prolonged exposure of humans to ambient particulate matter such as diesel exhaust
      particles (DEP) induces a variety of adverse health effects including
      cardiovascular diseases, asthma and cancer. Polycyclic aromatic hydrocarbons
      (PAHs) and their derivatives in DEP are thought to be potential candidates for
      the deleterious effects of DEP. We have identified 1,2-naphthoquinone (1,2-NQ) as
      a novel PAH quinone that contaminates DEP. Because 1,2-NQ is covalently bound to
      macromolecules through reactive thiols (thiolate ions), our rationale was that
      cellular proteins modified by 1,2-NQ seem to act as a redox-sensor and thus the
      interaction of thiol proteins with 1,2-NQ may disrupt their functions. To address
      our hypothesis, we prepared specific antibody against 1,2-NQ bound to proteins.
      In this review, we introduce an inhibitor of kappaB kinasebeta (IKKbeta) and
      protein tyrosine phosphatase 1B (PTP1B) as target molecules for 1,2-NQ. Although
      IKKbeta activates transcription factor NF-kappaB and PTP1B negatively regulates
      the receptor-protein tyrosine kinase, such as epidermal growth factor receptor
      (EGFR) in cells, covalent modification of these proteins caused by 1,2-NQ results
      in inhibition of NF-kappaB activity and transactivation of EGFR.

PMID- 18057785
TI  - [Molecular mechanism involved in chromium(VI) toxicity].
AB  - Chromium exists in many different oxidation states in the environment, Cr(VI) and
      Cr(III) being the most stable forms. Chromium has been known for over 100 years
      to be a human carcinogen. The greatest risk of cancer from chromium exposure is
      associated with Cr(VI). Cr(VI) enters cells via the sulfate anion transporter
      system and is reduced to intermediate oxidation states, such as Cr(V) and Cr(IV),
      in the process of forming stable Cr(III) forms. It is known that Cr(VI) affects
      expression of various genes. Metal responsive element-binding transcription
      factor-1 (MTF-1) is involved in sensing heavy metal load and the induced
      transcription of several protective genes, including metallothionein (MT)-I, MT
      II, zinc transporter-1, and gamma-glutamylcysteine synthetase. Cr(VI) inhibits
      zinc-induced MT transcription via modifying transactivation potential of MTF-1.
      However, the molecular mechanism for the Cr(VI)-mediated inhibition of MTF-1 has
      not been fully elucidated. In this review, I briefly summarize the previous
      studies and discuss the current status of research on Cr(VI) toxicity and Cr(VI)
      mediated inhibition against transcription.

PMID- 18057786
TI  - [Toxicogenomics as a tool for evaluation of chemical effects].
AB  - Concern about the toxicity of chemicals released into the environment has been
      increasing recently. Many chemicals are suspected to have hazardous effects, but
      evaluation of their toxicity is still difficult and challenging. One of these
      difficulties is the presence of chemicals that are reported to have an adverse
      effect on organisms despite negative results in conventional toxicity tests.
      Thus, a new technique has been desired in order to evaluate the effects of
      chemicals, Recent advances in molecular biology have provided a technique for
      better understanding the responses of organisms to chemicals; this emerging field
      is known as toxicogenomics. Toxicogenomics is defined as an integration of
      genomics (transcriptomics, proteomics, metabolomics) and toxicology. For example,
      the DNA microarray can be used to explore the gene expression profiles
      (transcriptomics) of organisms in response to chemicals. Exposure to chemicals
      results in characteristic gene expression profiles, suggesting that the DNA
      microarray can be used to evaluate chemical effects. Toxicogenomics is also
      expected to be useful in gaining a mechanistic understanding of these effects.
      Although it still has some limitations, this technique can be developed to assess
      chemicals.

PMID- 18057787
TI  - [Search for and structural elucidation of medicinal products from the vegetable
      kingdom (crude drugs and plant materials)].
AB  - This review describes chemical and biological studies on natural products
      achieved by the author for the latest 47 years and its main contents are composed
      of the following researches of the eight sections, entitled 1) Hopane-type
      triterpenes from a lichen, Parmelia leucotyliza, 2) Spirostanol and frostanol
      glycosides from Metanarthecium luteo-viride (Liliaceae), 3) Selective reduction
      of double bonds: preparation of 22,23-dihydroergosterol from ergosterol, 4)
      Compositions and structures of fragrant sesquiterpenes from several types of
      agarwoods, 5) Triterpenes and other components from Meliaceous plants, 6)
      Constituents of seeds of crude drugs and medicinal plants, 7) Hopane-type
      triterpene glycosides from a fern, Diplazium subsinuatum, 8) Search and
      structural elucidation of biologically active components from American plants
      obtained from United States of America (Oregon and California), Mexico,
      Guatemala, and Honduras. In this review, many classes of natural products, i.e.,
      terpenoids (mono-, sesqui-, di-, and triterpenoids), steroids, glycosides,
      saponins, tannins, phenylpropanoids, lignans, flavonoids (flavones, flavonols,
      flavanones, biflavones, flavan-3-ols, etc.), etc. are dealt with and referred to.

PMID- 18057788
TI  - [Oxidative stress and atherosclerosis].
AB  - Oxidative stress is a continuous level of oxidative damage in animal cells, which
      is caused by an overabundance of reactive oxygen species or a decline in
      antioxidant ability against them. Oxidative stress increases with individual risk
      factors of atherosclerosis such as obesity, hypertension, hyperlipidemia,
      diabetes and smoking. Thus, oxidative stress is considered to play a key role in
      the pathogenesis of atherosclerosis. This review discusses the relationship
      between oxidative stress and atherosclerosis based on findings from our research
      group. We have found that atherosclerotic lesions are formed in the aorta of mice
      fed a high-cholesterol and high-linoleic diet, in parallel with elevated serum
      lipid peroxide levels. This model is useful for primary screening of
      antiatherosclerotic agents with antioxidative activity. One notable factor in the
      development of atherosclerosis is oxidized low-density lipoprotein (OxLDL). In
      order to examine OxLDL levels in blood, we have developed anion-exchange HPLC
      methods using stepwise elution. Using these methods, we have found that OxLDL
      markedly increases in a rat model of metabolic syndrome, in animals exposed to
      cigarette smoke and in smokers in parallel with other oxidative stress markers.
      These oxidative stress markers have been attenuated by administration of several
      antioxidants. In addition, we have found that smoking accelerates atherogenesis
      in the aorta of apoE-deficient mice and this acceleration can be ameliorated by
      administration of vitamin E. These observations suggest that antioxidant
      supplementation may be an effective therapeutic strategy for metabolic syndrome
      and smoking-induced diseases in which elevated oxidative stress plays a pivotal
      role.

PMID- 18057789
TI  - [Development of high efficiency separation method for biomolecules].
AB  - It is becoming increasingly important to separate mixed samples, such as bio- and
      environmental samples. For the analysis of a target compound in a mixed sample, a
      highly efficient and selective separation method is required. We have developed
      columns of high resolution, very selective columns, and highly efficient
      analytical methods using integrated techniques and biomolecules. These developed
      methods save analytical time, sample volume, etc. We are now interested in nano
      scale materials which many people are now focusing on. Although excellent nano
      materials have been developed by many researchers, there are few efficient
      separation, purification or evaluation methods for these compounds. In this
      review, we introduce our recent achievements concerning the separation of nano
      compounds.

PMID- 18057790
TI  - [Effectiveness of network meeting system following practical pharmacy training].
AB  - We established a network meeting system program and used it to review a prior
      pharmaceutical practice training session. Pharmacists at Tokai University
      Hachioji Hospital gave lectures about dispensing and other tasks performed by
      clinical pharmacists to third-year undergraduate students at Tokyo University of
      Pharmacy and Life Sciences. After the lectures, discussions were held using the
      network meeting system, after which a questionnaire was completed by the
      students. The questionnaire was answered by 530 students, of whom approximately
      90% expressed interest in the program, 80% noted approval of the media used in
      the system, and 94% thought that the program was useful. Thus, we concluded that
      the students were motivated by the program to remember what they had learned in
      the lectures. We also found that the quality of data communication had an effect
      on the interests and motivation of the students. Based on their evaluation of the
      media, it was considered that improvements in communication regarding the system
      were necessary, though the evaluation of the utility of the program was not
      influenced by the quality of data communication. As a result, we concluded that
      our network meeting system program was useful to review prior learning of
      pharmaceutical practice.

PMID- 18057791
TI  - [Comparative study of drug efficacy and drug additives between generic drugs and
      original drugs].
AB  - In the present study, we tested three kinds of sleeping drugs, consisting mainly
      of triazolam, brotizolam, and flunitrazepam, to compare the drug efficacy of
      generic drugs with that of original drugs. After these drugs were administered
      orally to mice, drug efficacy was evaluated in terms of ambulation, onset time of
      sleep, and duration of sleep in the open field test. For all kinds of sleep
      inducing drugs, the drug efficacy of most generic drugs is not necessarily equal
      to that of the original drug. The main reason for the difference appears to be
      due to differences in the rate of absorption of the main drug. Any other
      differences between an original drug and a generic drug are caused by drug
      additives, the crystal form of the main drug, the formulation, and so on. In this
      study, the formulation was not the reason for the differences because all of the
      drugs were pulverized in a mortar and had no special coating. The drug additives
      for all the drugs are listed and the drug efficacy compared. Unfortunately, the
      information was not sufficient to shed any light on the differences in drug
      efficacy. For effective drug therapy, more information on drug additives should
      be provided.

PMID- 18057792
TI  - [Evaluation of efficacy and safety of manidipine hydrochloride among essential
      hypertensive patients: Substitution from branded product (Calslot) to Generic
      Product (Manidip)].
AB  - Calcium channel blockers are most commonly used in hypertensive patients in
      Japan. However, information on the efficacy and safety of generic calcium channel
      blockers is insufficient. The objective of the present study was to
      retrospectively evaluate the efficacy and safety of manidipine hydrochloride in
      21 essential hypertensive patients (mean age; 70.6+/-10.6 years, male/female;
      14/7) in Sendai Postal Services Agency Hospital who were switched (substituted)
      from a brand product (Calslot) to a generic product (Manidip). For this
      retrospective study, we used data from patient medical records and drug
      prescription information. Data from patients who were taking both types of
      manidipine hydrochloride, whose regimen were not changed for > 6 months before
      and after switching, and who provided informed consent were included in the
      analysis. Control values of blood pressure were not significantly different
      between before and after substitution (systolic/diastolic; from 137.9+/
      9.1/78.7+/-5.4 mmHg to 137.3+/-9.1/77.8+/-6.3 mmHg, p=0.73/p=0.36). The level of
      patient compliance for the antihypertensive drugs was also not different between
      before and after substitution (from 94.0+/-8.8% to 93.1+/-9.6%, p=0.72). There
      were 8 cases of adverse effects before substitution and 4 after substitution. No
      patient stopped taking the generic drug due to an adverse effect. In conclusion,
      significant differences in the efficacy, safety, and patient compliance were not
      observed between the brand product and generic product among patients who were
      switched from the brand product to the generic product.

PMID- 18057793
TI  - [In-vitro study of the drug interactions between Miglitol, an alpha-glucosidase
      inhibitor, and adsorbents].
AB  - The interactions between miglitol, an alpha-glucosidase inhibitor, and six
      adsorbents (carbon spheres, cholestyramine, colestimide, sevelamer hydrochloride,
      calcium polystyrene sulfonate, and sodium polystyrene sulfonate) were
      investigated in vitro. Miglitol corresponding to the minimum dose and adsorbents
      corresponding to the maximum dose were incubated at 37 degrees C for 180 min in
      solutions of pH 1.2 (gastric pH condition) and pH 6.8 (enteric pH condition),
      with and without the presence of carbohydrates, which were added to observe the
      effects on food adsorption. The adsorption ratio of miglitol to carbon spheres
      was 13.6% and 0% in pH 1.2 solution and 86.4% and 5.0% in pH 6.8 solution without
      and with the presence of carbohydrates, respectively. Thus, the adsorption ratio
      was higher in pH 6.8 solution. Adsorption of miglitol to calcium polystyrene
      sulfonate was nearly the same, 15.0-21.9%, at both pH. The adsorption ratio of
      miglitol to sodium polystyrene sulfonate was 43.4% and 45.5%, respectively, in pH
      1.2 solution without and with carbohydrates. In the pH 6.8 solutions, however,
      the respective adsorption ratios were low (5.2% and 11.3%). Miglitol did not
      adsorb to cholestyramine, sevelamer hydrochloride or colestimide under any pH
      condition examined. The above results suggest that miglitol adsorbs to carbon
      spheres and polystyrene sulfonic acid cation exchange resins. However,
      considering that miglitol is taken just before eating and thus exists in
      gastointestinal fluids together with food, and that the site of its effect is the
      upper small intestine, the interactions between miglitol and these adsorbents
      will most likely not be a problem.

PMID- 18057794
TI  - [Preparation and release profile of colon-targeting drug delivered as novel one
      step dry-coated tablets (OSDrC)].
AB  - One-Step Dry-Coated tablets (OSDrC) of a colon-targeting drug were prepared using
      Eudragit L 100-55 (Eud-L) and chitosan (Chit) as the outer layer. Lag time in the
      1st fluid, which simulated the stomach, was affected by differences in the pores
      occurring as a result of Chit dissolution. The dissolution rate of Chit was
      decreased by the addition of Eud-L. On the other hand, lag times in phosphate
      buffer (pH 7.4) simulating the small intestine, and in the 2nd fluid simulating
      the colon, were affected by differences in the pores occurring as a result of Eud
      L dissolution and Chit swelling. The lag time of OSDrC with an outer layer of Eud
      L:Chit at a ratio of 3:1 in each test medium was greater than the gastric
      emptying time in the 1st fluid and the small intestine transit time in phosphate
      buffer (pH 7.4). Furthermore, lag times were similar when test media were changed
      sequentially. Therefore, it is possible to deliver colon-targeting drugs as OSDrC
      with an outer layer of Eud-L:Chit at 3:1.

PMID- 18057795
TI  - [Effect of propolis on insulin resistance in fructose-drinking rats].
AB  - Propolis, a honeybee product, contains a variety of biologically active
      substances. The present study was designed to investigate the effects of propolis
      on insulin resistance induced by fructose-drinking rats (FDR; type 2 diabetic
      animal model). Male Wistar rats (6 weeks old) received 15% fructose solution in
      drinking water for 8 weeks. FDR showed significant increases in plasma levels of
      insulin, Homeostasis Model Assessment ratio (HOMA-R, an index of insulin
      resistance), body weight, and systolic blood pressure but not blood glucose
      levels, when compared with control rats. Brazilian propolis extract (100 and 300
      mg/kg, p.o.) treatment for 8 weeks significantly decreased the plasma level of
      insulin, HOMA-R, and body weight, increased plasma triglyceride levels without
      affecting blood glucose and total cholesterol levels, and tended to decrease
      systolic blood pressure. In isolated and perfused mesenteric vascular beds of
      FDR, propolis treatment resulted in a significant reduction of sympathetic nerve
      mediated vasoconstrictor response to periarterial nerve stimulation (PNS; 8 Hz)
      and tended to increase the calcitonin gene-related peptide (CGRP) nerve-mediated
      vasodilator response to PNS, compared with those in untreated FDR. However,
      propolis treatment did not significantly affect norepinephrine-induced
      vasoconstriction and CGRP-induced vasodilation. These results suggest that
      propolis could be an effective functional food to prevent the development of
      insulin resistance.

PMID- 18057796
TI  - [Basic study to establish medication safety culture with patient-commitment style
      in community pharmacy: An examination from meeting reports].
AB  - Our group conducted a Medication Safety Culture Building Drive, enlisting the
      cooperation of pharmacy patients to clarify obstacles and verify the effect of
      the measures implemented. Pharmacists at 38 community pharmacies instituted a 3
      month trial period of rigorous prescription confirmation by checking filled
      prescriptions against the accompanying drug information (DI) in the presence of
      patients at pharmacy counters, whenever prescription drugs were dispensed. During
      the first month, 29 pharmacies reported carrying out the program with the rate of
      patient coverage was over 50%; while 8 others reported that rate of patient
      coverage was less than 50%. Factors standing in the way of checking filled
      prescriptions with the patients could be characterized as "physical conditions,"
      "prescription content," or "patient attributes." The measures devised to counter
      these obstacles all fell within the categories of "education of patients and
      pharmacists," "advance arrangements made in preparation for checking," "methods
      of checking and nature of items checked," "checking procedure," and "DI
      literature." After three month, 34 pharmacies reported that the effort had been
      effective. During the three months, the average implementation rate (patient
      coverage rate) was improved from 92.5% in April to 96.5% in June (p<0.001). The
      specific qualitative effects listed below were among those mentioned in reports
      compiled from meetings. 1) Improvement of patients' and pharmacists' awareness
      regarding dispensing error prevention, 2) Increase in patients' interest in, and
      understanding of, their own prescription medications, 3) Increase in patients'
      understanding about the efforts and in number of patients cooperating with the
      effort.

PMID- 18057797
TI  - [Analysis of censored data in multi-factorial analgesic test].
AB  - Animal pain testing is essential for the development of new analgesic drugs,
      where appropriate data analyses as well as appropriate multi-factorial design of
      experiments are necessary to obtain meaningful results in an efficient fashion.
      The tail withdrawal experiment is one of the pain tests in which a rhesus monkey
      is restrained in a chair from which its tail hangs free by so it can be immersed
      in warm water. The monkeys consistently kept their tails in 38-40 degrees C water
      for an extended period of time, and thus, the data were censored at 120 sec. The
      effect of temperature on the tail withdrawal latency was evaluated using three
      monkeys with a randomized block design. The effect of morphine on the thermal
      sensitivity was also evaluated. A Friedman-type two-way analysis of variance
      (Mack-Skillings test) demonstrated that the effects of both temperature and the
      animals were significant. The effect of repeated measurement in one animal was
      not significant using the Friedman test, indicating that the significance of the
      effect of animals could be attributed to the difference in the intrinsic thermal
      sensitivity between animals. This method, together with a graphical approach, may
      prove to be valuable for assessing the sensitivity and reproducibility of an
      experimental condition, as well as the pharmacological effects of analgesic
      drugs.

PMID- 18057798
TI  - [Quality evaluation of magnesium oxide tablets using acid neutralization test and
      dissolution test].
AB  - For the purpose of quality evaluation of commercially available magnesium oxide
      (MgO) tablets, we studied their acid neutralization and dissolution behaviors.
      The dissolution test was carried out by the paddle method in 1st fluid (pH 1.2).
      The dissolution amount of MgO from tablets was determined by chelatometric
      titration. The medium pH was periodically measured. The neutralization reaction
      in 750 ml of 1st fluid was markedly different between two kinds of commercial
      tablets. The pH of medium including Magmit tablet reached 8.9 and the dissolution
      rate of MgO was 81.1% after 20 min. Contrariwise, the final pH of medium
      including Maglax tablet was 2.5 and the dissolution rate of MgO was 77.1% after
      60 min. These results indicate that the dissolution rate of MgO from tablets
      should be >81.1% to obtain significant acid neutralization action.

PMID- 18057799
TI  - [Relation between comprehensive-geriatric assessment and the ability of self
      administration in elderly diabetic patients].
AB  - Intellectual ability of self-administration plays a crucial role in a diabetes
      regimen. However, in many cases, self-administration is considered difficult,
      because of the impairment of activities of the individual's daily living (ADL),
      instrumental ADL and cognitive function. To assess comprehensive-geriatric
      assessment (CGA) in elderly diabetic sufferers, 62 elderly inpatients and
      outpatients aged over 70 years were investigated. CGA includes Barthel index
      (BI), Mini-mental-state-examination (MMSE) and the Tokyo Metropolitan Institute
      of Gerontology index of competence (TMIGIC). The relation of ability to self
      administer and CGA was examined. In oral therapy, there was significant
      difference between self-administration and non-self-administration in MMSE
      (p=0.0065), BI (p=0.0219) and TMIGIC (p=0.0053). Among these indexes, TMIGIC was
      the most sensitive index in oral therapy. In insulin therapy, there was also
      significant difference between self-administration and non-self-administration:
      MMSE (p=0.00042), BI (p=0.000019) and TMIGIC (p=0.0019). Among these indexes, BI
      was the most sensitive index in insulin therapy. It was suggested that CGA was
      useful to assess the ability of self-administration in elderly diabetic patients.

PMID- 18057800
TI  - [Assessment of learning activities using streaming video for laboratory practice
      education: aiming for development of E-learning system that promotes self
      learning].
AB  - In order to develop an e-learning system that promotes self-learning, lectures
      and basic operations in laboratory practice of chemistry were recorded and edited
      on DVD media, consisting of 8 streaming videos as learning materials. Twenty-six
      students wanted to watch the DVD, and answered the following questions after they
      had watched it: "Do you think the video would serve to encourage you to study
      independently in the laboratory practice?" Almost all students (95%) approved of
      its usefulness, and more than 60% of them watched the videos repeatedly in order
      to acquire deeper knowledge and skill of the experimental operations. More than
      60% answered that the demonstration-experiment should be continued in the
      laboratory practice, in spite of distribution of the DVD media.

PMID- 18057802
TI  - Emerging occupational hazards among health care workers in the new millennium.

PMID- 18057801
TI  - Endothelial cells constituting blood-nerve barrier have highly specialized
      characteristics as barrier-forming cells.
AB  - In autoimmune disorders of the peripheral nervous system (PNS) such as Guillain
      Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy,
      breakdown of the blood-nerve barrier (BNB) has been considered as a key step in
      the disease process. Hence, it is important to know the cellular property of
      peripheral nerve microvascular endothelial cells (PnMECs) constituting the bulk
      of BNB. Although many in vitro models of the blood-brain barrier (BBB) have been
      established, very few in vitro BNB models have been reported so far. We isolated
      PnMECs from transgenic rats harboring the temperature-sensitive SV40 large T
      antigen gene (tsA58 rat) and investigated the properties of these "barrier
      forming cells". Isolated PnMECs (TR-BNBs) showed high transendothelial electrical
      resistance and expressed tight junction components and various types of influx as
      well as efflux transporters that have been reported to function at BBB.
      Furthermore, we confirmed the in vivo expression of various BBB-forming
      endothelial cell markers in the endoneurium of a rat sciatic nerve. These results
      suggest that PnMECs constituting the bulk of BNB have a highly specialized
      characteristic resembling the endothelial cells forming BBB.

PMID- 18057803
TI  - Health problems and the use of health services among physicians: a review article
      with particular emphasis on Norwegian studies.
AB  - This paper provides an overview of recent Norwegian and international research
      into physicians' health problems and their use of health services, with a
      particular focus on more recent studies relating to The Norwegian Physicians'
      Survey. The review suggests that physicians' physical health is similar to the
      general population, although female physicians tend to be in better health than
      other women. Some mental disorders such as depression and suicide appear to be
      more prevalent. Mental health problems are known to be associated with low work
      control (autonomy), time pressure and demanding patients. There is little
      difference between the genders early in their career, but more female than male
      physicians seem to experience problems later on. Physicians seldom take sick
      leave, and tend to make less use of primary health care and some screening
      facilities. Self-treatment is common -- even for mental problems. American
      impaired physician programmes have demonstrated high recovery rates (70-80%), and
      increasing emphasis is now being placed on psychiatric diagnoses. As certain
      mental disorders appear to be common among physicians, specialist psychiatric
      services should be made more accessible for this group. A low-threshold facility
      for seeking help with such problems has recently been developed in Norway (the
      Villa Sana Resource Centre).

PMID- 18057804
TI  - Occupational health problems in modern dentistry: a review.
AB  - Despite numerous technical advances in recent years, many occupational health
      problems still persist in modern dentistry. These include percutaneous exposure
      incidents (PEI); exposure to infectious diseases (including bioaerosols),
      radiation, dental materials, and noise; musculoskeletal disorders; dermatitis and
      respiratory disorders; eye injuries; and psychological problems. PEI remain a
      particular concern, as there is an almost constant risk of exposure to serious
      infectious agents. Strategies to minimise PEI and their consequences should
      continue to be employed, including sound infection control practices, continuing
      education and hepatitis B immunisation. As part of any infection control
      protocols, dentists should continue to utilise personal protective measures and
      appropriate sterilisation or other high-level disinfection techniques. Aside from
      biological hazards, dentists continue to suffer a high prevalence of
      musculoskeletal disorders (MSD), especially of the back, neck and shoulders. To
      fully understand the nature of these problems, further studies are needed to
      identify causative factors and other correlates of MSD. Continuing education and
      investigation of appropriate interventions to help reduce the prevalence of MSD
      and contact dermatitis are also needed. For these reasons, it is therefore
      important that dentists remain constantly informed regarding up-to-date measures
      on how to deal with newer technologies and dental materials.

PMID- 18057805
TI  - Organizational climate and nurse health outcomes in the United States: a
      systematic review.
AB  - Increasing interest has been focused on understanding the role working conditions
      play in terms of the serious issues facing hospitals today, including quality of
      patient care, nurse shortages, and financial challenges. One particular working
      condition that has been the subject of recent research, is the impact of
      organizational climate on nurses' well-being, including occupational health
      outcomes. To examine evidence-based research on the association between
      organizational climate and occupational health outcomes among acute-care
      registered nurses, a systematic review of published studies was conducted.
      Studies assessing the association between organizational climate variables and
      three common health outcomes in nurses (blood/body fluid exposures,
      musculoskeletal disorders, and burnout) were reviewed. Fourteen studies met the
      inclusion criteria. Although most were cross-sectional in design and variability
      was noted across studies with respect to operational definitions and assessment
      measures, all noted significant associations between specific negative aspects of
      hospital organizational climate and adverse health impacts in registered nurses.
      While evidence for an association between organizational climate constructs and
      nurses' health was found, data were limited and some of the relationships were
      weak. Additional studies are warranted to clarify the nature of these complex
      relationships.

PMID- 18057806
TI  - A review of low back pain and musculoskeletal disorders among Italian nursing
      personnel.
AB  - This review targeted all research previously conducted on the topic of
      musculoskeletal disorders among Italian nursing personnel, with a particular
      focus on studies that had examined individual, physical and psychosocial risk
      factors. Scientific literature published in both English and Italian languages
      was searched using electronic and manual techniques. A total of 25 appropriate
      studies were located and examined, most of which had focused on the prevalence of
      low back pain (LBP) among nurses. From the review, it was shown that LBP
      prevalence rates have varied widely among different investigations conducted in
      Italy, ranging from 33% to 86%. Previous studies also suggest that female gender,
      physical factors and psychosocial factors are important LBP risk factors in this
      country. Since most of the data currently available describes nurses working in
      the northern and central regions only, further investigations should now be
      undertaken in southern Italy, in order to obtain a more complete overview of the
      problem from a national perspective. Furthermore, a standardized method for
      measuring these conditions is strongly recommended for future Italian research,
      to allow better local and international comparison of the data.

PMID- 18057807
TI  - Prevention of irritant contact dermatitis among health care workers by using
      evidence-based hand hygiene practices: a review.
AB  - Irritant contact dermatitis is often found on the hands of healthcare workers and
      is generally caused by frequent hand washing, gloves, aggressive disinfectants or
      detergents. Alcohols have only a marginal irritation potential, although they may
      cause a burning sensation on pre-irritated skin. A burning sensation when using
      alcohols therefore, suggests that the skin barrier is already damaged. Two
      options for hand hygiene are generally available in clinical practice: (1) hand
      washing with some type of soap and water or (2) hand disinfection with alcohol
      based hand rubs. Most clinical situations require the use of an alcohol-based
      hand rub for decontamination, which is especially useful for reducing the
      nosocomial transmission of various infectious agents. Washing one's hands should
      be the exception, to be performed only when they are visibly soiled or
      contaminated with proteinaceous material, or visibly soiled with blood or other
      body fluids. The overall compliance rate in hand hygiene is around 50%, which is
      far too low. In addition, healthcare workers quite often wash their hands with
      soap and water, when they should use an alcohol-based hand rub. This not only
      adds to the degree of skin irritation, but is also potentially dangerous for
      patients, due to the low efficacy of hand washing when compared to hand
      disinfection with alcohol rubs. Adhering to evidence-based hand hygiene protocols
      and following international guidelines on hand hygiene practices therefore, can
      help prevent irritant contact dermatitis among healthcare workers.

PMID- 18057808
TI  - Concerns and preparedness for an avian influenza pandemic: a comparison between
      community hospital and tertiary hospital healthcare workers.
AB  - Little is known about differences in levels of concerns or preparedness for an
      avian influenza (AI) pandemic among healthcare workers (HCWs) in different types
      of hospitals. We compared these concerns and preparedness between 326 HCWs of two
      community hospitals (CHs) and 908 HCWs from a tertiary hospital (TH) using a self
      administered questionnaire between March-June 2006. Response rates were 84.2% and
      80.0% from the CHs and TH. Most HCWs (71.6%) felt prepared for an AI outbreak and
      had significant concerns. They perceive an AI pandemic having adverse impacts on
      their personal life and work, such as people avoiding them (57.1%). A greater
      percentage of TH compared to CH HCWs expressed concerns such as feeling their
      jobs put them at great AI exposure (78.3% vs 67.5%, p=0.012). TH HCWs were more
      likely to report participating in readiness preparation activities, such as
      training for infection control (90.0% vs 82.2%, p=0.014) and feel that they
      (74.1% vs 64.7%, p=0.045) and their hospital (86.8% vs 71.8%, p=0.000) were
      prepared for an outbreak. Healthcare institutions need to include personal,
      psychological and family concerns on the agenda and increase participation in
      readiness preparation activities among HCWs to help prepare for such future
      crises.

PMID- 18057809
TI  - Job stress in young physicians with an emphasis on the work-home interface: a
      nine-year, nationwide and longitudinal study of its course and predictors.
AB  - Although physicians are known to experience more stress than other workers,
      knowledge is lacking on the course of stress from a longitudinal perspective.
      This study explored the course of and contributors to, different dimensions of
      early career job-stress among physicians by means of a nationwide mail survey,
      with a particular emphasis on stress relating to the work-home interference. All
      physicians graduating from all four Norwegian universities in 1993 / 94 (N=631),
      responded during their final year of medical school (N=522), during their
      internship (N=402), in their 4th postgraduate year (N=422), and in their 10th
      postgraduate year (N=390). The mean observation period was 9.2 yr (SD=0.5). The
      main outcomes were job stress dimensions derived from an established job stress
      questionnaire (Cooper / Tyssen), with emphasis placed on dimensions of the work
      home interference. Stress relating to the work-home interference increased during
      the observation period for both genders (repeated measures: beta=0.06, p<0.05),
      whereas stress relating to emotional pressure, time pressure, and fear of
      complaints and criticism, decreased. Stress relating to the work-home
      interference increased during their early career, mainly due to a lack of
      adaptive reduction in work hours and an increased number of children.
      Neuroticism, conscientiousness, and lack of support from one's partner and
      colleagues, appeared to be predictive of this stress.

PMID- 18057810
TI  - Minnesota nurses' study: perceptions of violence and the work environment.
AB  - Work-related violence is an important problem worldwide, and nurses are at
      increased risk. This study identified rates of violence against nurses in
      Minnesota, USA, and their perceptions of the work environment. A sample of 6,300
      randomly selected nurses described their experience with work-related violence in
      the previous year. Differences in perceptions of the work environment and work
      culture were assessed, based on a nested case-control study, comparing nurses who
      experienced assault to non-assaulted nurses. Annual rates of physical and non
      physical assault, per 100 nurses, were 13.2 (95% CI: 12.2-14.3), and 38.8 (95%
      CI: 37.4-40.4). Cases were more likely than controls to report: higher levels of
      work stress; that assault was an expected part of the job; witnessing all types
      of patient-perpetrated violence in the previous month; and taking corrective
      measures against work-related assault. Controls versus cases were more likely to
      perceive higher levels of morale, respect and trust among personnel, and that
      administrators took action against assault. Nurses frequently experienced work
      related violence, and perceptions of the work environment differed between nurses
      who had experienced physical assault, and those who had not. Employee safety,
      morale, and retention are particularly important in light of the nursing
      shortage, and knowledge of nurses' perceptions will assist in tailoring
      interventions aimed at reducing the substantial risk of physical assault in
      health care settings.

PMID- 18057811
TI  - Design of the Japan Nurses' Health Study: a prospective occupational cohort study
      of women's health in Japan.
AB  - The Japan Nurses' Health Study (JNHS) is a prospective occupational cohort study
      investigating the effects of lifestyle and healthcare practices on women's
      health. It was initiated in 2001, with a six-year entry period and a proposed ten
      year follow-up. Participants comprise female registered nurses, licensed
      practical nurses, public health nurses, and midwives, aged 25 yr or over at the
      baseline survey. Participants were recruited in cooperation with the Japanese
      Nursing Association and the Japan Menopause Society. A self-administered baseline
      questionnaire was distributed, requesting demographic information, lifestyle
      factors, pharmaceutical drug use, physical condition, reproductive health, and
      disease history. A total of 49,914 women from all 47 prefectures in Japan
      responded to the baseline survey. Among them, approximately 18,000 agreed to be
      followed-up, and returned signed informed-consent sheets, together with their
      completed baseline questionnaires. Changes in lifestyle, healthcare, incidence of
      disease, and health outcomes over time will now be studied. The cohort receives
      annual JNHS newsletters and biennial follow-up questionnaires by mail.

PMID- 18057812
TI  - Prevalence of diseases and statistical power of the Japan Nurses' Health Study.
AB  - The Japan Nurses' Health Study (JNHS) is a long-term, large-scale cohort study
      investigating the effects of various lifestyle factors and healthcare habits on
      the health of Japanese women. Based on currently limited statistical data
      regarding the incidence of disease among Japanese women, our initial sample size
      was tentatively set at 50,000 during the design phase. The actual number of women
      who agreed to participate in follow-up surveys was approximately 18,000. Taking
      into account the actual sample size and new information on disease frequency
      obtained during the baseline component, we established the prevalence of past
      diagnoses of target diseases, predicted their incidence, and calculated the
      statistical power for JNHS follow-up surveys. For all diseases except ovarian
      cancer, the prevalence of a past diagnosis increased markedly with age, and
      incidence rates could be predicted based on the degree of increase in prevalence
      between two adjacent 5-yr age groups. The predicted incidence rate for uterine
      myoma, hypercholesterolemia, and hypertension was > or =3.0 (per 1,000 women, per
      year), while the rate of thyroid disease, hepatitis, gallstone disease, and
      benign breast tumor was predicted to be > or =1.0. For these diseases, the
      statistical power to detect risk factors with a relative risk of 1.5 or more
      within ten years, was 70% or higher.

PMID- 18057813
TI  - Non-hospital based registered nurses and the risk of bloodborne pathogen
      exposure.
AB  - The aim of this study was to assess the risk of blood and body fluid exposure
      among non-hospital based registered nurses (RNs) employed in New York State. The
      study population was mainly unionized public sector workers, employed in state
      institutions. A self-administered questionnaire was completed by a random
      stratified sample of members of the New York State Nurses Association and
      registered nurse members of the New York State Public Employees Federation.
      Results were reviewed by participatory action research (PAR) teams to identify
      opportunities for improvement. Nine percent of respondents reported at least one
      needlestick injury in the 12-month period prior to the study. The percutaneous
      injury (PI) rate was 13.8 per 100 person years. Under-reporting was common; 49%
      of all PIs were never formally reported and 70% never received any post-exposure
      care. Primary reasons for not reporting included: time constraints, fear, and
      lack of information on reporting. Significant correlates of needlestick injuries
      included tenure, patient load, hours worked, lack of compliance with standard
      precautions, handling needles and other sharps, poor safety climate, and
      inadequate training and availability of safety devices (p<0.05). PAR teams
      identified several risk reduction strategies, with an emphasis on safety devices.
      Non-hospital based RNs are at risk for bloodborne exposure at rates comparable to
      hospital based RNs; underreporting is an important obstacle to infection
      prevention, and primary and secondary risk management strategies appeared to be
      poorly implemented. Intervention research is warranted to evaluate improved risk
      reduction practices tailored to this population of RNs.

PMID- 18057814
TI  - Musculoskeletal complaints among Italian X-ray technologists.
AB  - The aim of this study was to determine the prevalence of musculoskeletal
      complaints among X-ray technologists and to examine their relationship with
      physical and psychosocial factors. A cross-sectional study was performed in 2006
      among 203 X-ray technologists working in 13 hospitals in the Apulia region of
      southern Italy. A questionnaire was used to collect data on personal
      characteristics, physical workload, psychosocial aspects, and the presence of
      musculoskeletal symptoms in the neck, shoulders, low back, hand/wrist and legs.
      Univariate analyses and multiple logistic regression analyses were then
      performed. The prevalence of complaints at any body site in the previous 12
      months was 67%. Low back pain was the most commonly reported symptom (59.6%),
      followed by shoulder (21.2%), neck (19.7%), leg (13.8%) and hand/wrist pain
      (12.3%). Age was associated with low back pain, while high physical workload was
      associated with symptoms in the neck, low back and hand/wrist. High job demands
      were associated with neck and shoulder pain. Overall, our study suggests high
      prevalence rates of musculoskeletal complaints may exist among Italian X-ray
      technologists. Physical workload, psychosocial and individual factors appear to
      be important risk factors for musculoskeletal disorders within this occupational
      group.

PMID- 18057815
TI  - The impact of self-perceived job stress on menstrual patterns among Taiwanese
      nurses.
AB  - The purpose of this study was to assess the impact of self-reported job stress on
      menstrual patterns among nurses. We conducted a cross-sectional survey of nursing
      staff from five psychiatric institutions and four general hospitals in Taiwan. A
      total of 746 participants were eligible for the final analysis, among whom, 72.3%
      were ascertained as having a self-perceived high level of job stress. Self
      perceived high job stress was significantly associated with irregular menstrual
      cycles [Adjusted odds ratio (AOR): 4.8, 95% confidence interval (CI): 3.3-7.2]
      and longer menstrual bleeding periods (more than 7 d) [AOR: 2.5, 95% CI: 1.7
      3.7], but was not significantly related to long or short menstrual cycles.
      Overall, this study suggests that nurses' self-perceived job stress may be
      associated with certain aspects of menstrual dysfunction. Further investigations
      with prospective follow-up studies and urine hormonal measurements are now
      recommended to provide additional insight into the pathophysiological mechanisms
      of our findings.

PMID- 18057816
TI  - Degradation of phenanthrene on plant leaves by phyllosphere bacteria.
AB  - The activity of phyllosphere bacteria in the degradation of phenanthrene was
      investigated as a mechanism for the removal of atmospheric phenanthrene after its
      deposition on plant leaves. Initially, leaf samples of six plant species were
      collected from two roadsides in Bangkok to determine the presence of phenanthrene
      degrading bacteria. The numbers of phenanthrene-degrading phyllosphere bacteria
      were varied and ranged from 3.5 x 10(4) to 1.95 x 10(7) CFU/g, in which the
      highest number was found from Ixora sp. Further studies were carried out in the
      laboratory by spraying phenanthrene on Ixora sp. leaves and then monitoring the
      amount of deposited phenanthrene and number of phenanthrene-degrading bacteria
      after incubation. The results showed that the amount of phenanthrene was
      significantly reduced on leaves containing phenanthrene-degrading bacteria. These
      were detected along with a rapid increase in the number of bacteria on leaves.
      The results indicated that many phyllosphere bacteria could utilize phenanthrene
      to support their growth and thereby reduce the amount of deposited phenanthrene
      on leaf surfaces. Several phenanthrene-degrading bacteria were later isolated
      from the leaves and identified with a high 16S rDNA sequence similarity to the
      genera Pseudomonas, Microbacterium, Rhizobium, and Deinococcus.

PMID- 18057817
TI  - Associations between the use of antimicrobial agents for growth promotion and the
      occurrence of antimicrobial-resistant Escherichia coli and enterococci in the
      feces of livestock and livestock farmers in Japan.

PMID- 18057818
TI  - Cryptococcus tibetensis sp. nov., a novel basidiomycetous anamorphic yeast
      species isolated from plant leaves.

PMID- 18057819
TI  - Micromonospora narathiwatensis sp. nov., from Thai peat swamp forest soils.

PMID- 18057820
TI  - Isolation and characterization of bacteria capable of producing pyridoxamine (PM)
      and pyridoxamine 5'-phosphate (PMP), vitamin B6 compounds.

PMID- 18057821
TI  - Gluconobacter kondonii sp. nov., an acetic acid bacterium in the alpha
      Proteobacteria.

PMID- 18057822
TI  - Means to mediating accumulation of hydrophobin-like proteins in the wall of
      Beauveria bassiana conidia for improved tolerance to thermal stress.

PMID- 18057823
TI  - Evaluation of immunochromatographic assay for serodiagnosis of Brucella canis.
AB  - Canine brucellosis is a contagious disease with venereal and oral modes of
      transmission that produces late abortion in females, epididymides and prostates
      in males. Diagnosis is difficult because of unstable serum antibody titers that
      vary from individual to individual as well as between different methods used for
      their detection. The objective of this work was to evaluate the clinical utility
      of the immunochromatographic assay (ICA) for serodiagnosis of dogs suspected of
      having brucellosis, and results were compared with those obtained for hemoculture
      (HC) and the rapid screening agglutination with 2-mercaptoethanol (2-ME RSAT).
      The all experimentally infected dogs were positive in ICA, HC and 2-ME RSAT from
      5 weeks, 7 weeks, and 3 weeks after infection, respectively. Also, among dogs
      selected from 10 different breed kennels occurred brucellosis, 24.8%, 39.5% and
      39.1% of dogs tested were detected as positive with HC, 2-ME RSAT and ICA,
      respectively. The kappa value between 2-ME RSAT and ICA was 0.89. The results of
      this study showed that sensitivity and specificity of the ICA are comparable with
      those obtained using conventional serological and bacteriological test for
      brucellosis. In conclusion, the ICA kit provides a handy and accurate tool for
      the rapid serodiagnosis of canine brucellosis.

PMID- 18057824
TI  - Pathology of the testicle and sex accessory glands following the administration
      of boldenone and boldione as growth promoters in veal calves.
AB  - Boldenone and its precursor Boldione are illegally used for anabolic purposes in
      humans, horses and cattle. To develop more effective policies and programs to
      maximize food security, Italian Public Health Services investigate all indicators
      capable of assisting the recognition of treated animals, and prioritize research
      and the formulation of action strategies for the promotion of healthy eating.
      Thus, an experimental administration of boldenone and boldione at anabolic
      dosages in veal calves was carried out to evaluate the changes in target organs
      by qualitative and semi-quantitative morphological analysis. The lesions
      resembled the effects already observed after the administration of androgen
      hormones to cattle. Main findings were represented by prostate hypersecretion,
      increased rate of apoptotic cells and decreased rate of Ki67 positive cells in
      the germ cell line of treated animals, particularly in boldione group and finally
      some new features like hypertrophy of the prostate urothelial cells.

PMID- 18057825
TI  - Prognostic significance of surgical margin, Ki-67 and cyclin D1 protein
      expression in grade II canine cutaneous mast cell tumor.
AB  - The prognosis for canine cutaneous mast cell tumor (CCMT) is thought to be
      correlated with histopathological grading. However, the wide variety of
      histopathologic types of grade II is one of the most troublesome and difficult
      points for prognosis. The objective of this study is to determine the prognostic
      value of surgical margin, ki-67 and cyclin D1 protein expression in grade II
      tumor. Surgically resected specimens of solitary grade II CCMT from 48 dogs with
      follow-up periods over 360 days (median was 1080 days) were used in this study.
      The expression of cyclin D1 and ki-67 proteins was determined by morphometrically
      using slides stained immunocytochemically, and the correlations among the
      results, survival rate, and recurrence and/or metastasis rate of each dog were
      analyzed statistically. The recurrence and/or metastasis and mortality rate in
      the incomplete surgical excision group within 30 months postoperatively were
      higher than that of the complete surgical excision group. In the incomplete
      surgical excision group, dogs with low positive staining of ki-67 had a
      significantly better survival, but the recurrence and metastasis rate and ki-67
      positivity failed to show a significant correlation. Only a small number of cases
      showed cyclin D1-positive tumor cells, but most of them had a poor outcome with a
      high recurrence rate. In grade II CCMT, incomplete excision induced a relatively
      high metastasis rate and poor prognosis. Ki-67 positivity is a marker for the
      estimation of overall survival in incomplete surgical excision cases. Cyclin D1
      positivity was low and may not have a prognostic role.

PMID- 18057826
TI  - Immunohistochemical study on the delayed progression of epithelial apoptosis in
      follicle-associated epithelium of rat Peyer's patch.
AB  - It is well known that some caspases in apoptosis is involved in determinant of
      terminal differentiation and maturation of various cells. Our previous study
      ultrastructurally clarified the differentiation into M cells from immature
      microvillous epithelial cells and the redifferentiation from M cells to
      microvillous epithelial cells in the follicle-associated epithelium (FAE) of rat
      Peyer's patch. In this study, the difference of epithelial apoptosis between the
      FAE of Peyer's patch and intestinal villi was immunohistochemically investigated
      in rat jejunoileum. As a result, cleaved caspase-3 was limited to several
      epithelial cells at the tip of FAE, whereas almost all of the epithelial cells
      were cleaved caspase-3 positive in intestinal villi. Cleaved caspase-9 was
      detected only in a few exfoliating or exfoliated epithelial cells of both FAE and
      intestinal villi. Nuclear DNA-fragmentation was detected only in several
      epithelial cells of the tip of FAE, while it was expressed from the middle
      regions in the intestinal villi. The DNase I expression of the epithelial
      cytoplasm was much weaker in FAE than in intestinal villi. Bcl-x expression was
      restricted in the apical cytoplasms of epithelial cells in the FAE, whereas it
      was restricted in whole cytoplasms in villous epithelial cells. These findings
      suggest that the progression of the apoptotic process in the epithelial cells of
      FAE is later than in the intestinal villi, so that the possibility of epithelial
      differentiation might be remained in the FAE, unlike in the intestinal villi.

PMID- 18057827
TI  - Age-related changes in ionized calcium-binding adapter molecule 1
      immunoreactivity and protein level in the gerbil hippocampal CA1 region.
AB  - Microglia are evenly distributed throughout the brain parenchyma. They respond
      rapidly to a variety of alterations in the microenvironment of the brain and act
      as sensors for pathological events in the brain. In the present study, we
      investigated the age-dependent changes in the immunoreactivity and protein level
      of ionized calcium-binding adapter molecule 1 (Iba-1), a microglial marker, in
      the CA1 region of the gerbil hippocampus. Iba-1 immunoreactive microglia were
      detected in the hippocampal CA1 region of the postnatal month 1 (PM 1) group. Iba
      1 positive microglia were morphologically inactive between the PM 1 and PM 12
      stages. Some Iba-1 immunoreactive microglia were present in the active form in
      the hippocampal CA1 region of the PM 18 and PM 24 groups. The Iba-1 protein
      levels in hippocampal CA1 homogenates were decreased in the PM 1 through PM 6
      groups and increased in an age-dependent manner thereafter. These results suggest
      that Iba-1 immunoreactive microglia in the active form were detected in the
      hippocampal CA1 region in the PM 18 and PM 24 groups. This result may be
      associated with an age-dependent susceptibility to neurodegenerative diseases
      associated with the hippocampus.

PMID- 18057828
TI  - Diluted isoflurane as a suitable alternative for diethyl ether for rat
      anaesthesia in regular toxicology studies.
AB  - Despite its explosive properties and toxicity to both animals and humans, diethyl
      ether is an agent long used in Japan in the anaesthesia jar method of rat
      anaesthetises. However, in response to a recent report from the Science Council
      of Japan condemning diethyl ether as acceptable practice, we searched for an
      alternative rat anaesthesia method that provided data continuous with pre
      existing regular toxicology studies already conducted under diethyl ether
      anaesthesia. For this, we examined two candidates; 30% isoflurane diluted with
      propylene glycol and pentobarbitone. Whereas isoflurane is considered to be one
      of the representatives of modern volatile anaesthetics, the method of propylene
      glycol-diluted 30% isoflurane used in this study was our modification of a
      recently reported method revealed to have several advantages as an inhalation
      anaesthesia. Intraperitoneal pentobarbitone has long been accepted as a humane
      method in laboratory animal anaesthesiology. These 2 modalities were scrutinized
      in terms of consistency of haematology and blood chemistry with previous results
      using ether. We found that pentobarbitone required a much longer induction time
      than diethyl ether, which is suspected to be the cause of fluctuations in several
      haematological and blood chemical results. Conversely, only calcium ion
      concentration showed a slight difference from traditional results in the case of
      30% isoflurane. Additionally, serum prolactin and corticosterone levels indicated
      that 30% isoflurane induced less stress than ether, confirming that 30%
      isoflurane can both provide results consistent with diethyl ether, while at the
      same time remove its disadvantages. As such 30% isoflurane appears to be a strong
      alternative anaesthetic agent for future regular toxicology studies in Japan.

PMID- 18057829
TI  - Genetic analysis of phosphoprotein and matrix protein of rabies viruses isolated
      in Brazil.
AB  - To investigate the genetic characteristics of phosphoprotein (P) and matrix
      protein (M) genes of variable rabies virus (RV) prevalent in Brazil, the authors
      genetically characterized the P and M genes from 30 Brazilian RV field isolates.
      Phylogenetic analysis based on the P and M genes revealed the presence of six RV
      variants that consisted primarily of three insectivorous bats, the vampire bat,
      dog and fox in Brazil. Specific amino acid substitutions corresponding to these
      phylogenetic lineages were observed, with Asp(42) and Glu(62) in the P protein
      found to be characteristic of Brazilian chiroptera- and carnivora-related RVs,
      respectively. Amino acid sequence motifs predicted to associate with a viral
      function in the P and M proteins were conserved among Brazilian RV variants.

PMID- 18057830
TI  - Pathology of canine oral malignant melanoma with cartilage and/or osteoid
      formation.
AB  - Of 197 cases of canine oral malignant melanoma, 29 cases with myxoid, cartilage,
      and osteoid formation were studied pathologically and immunohistochemically.
      Tumor tissues were classified into spindle cell type (13 cases), epithelioid cell
      type (1 case), and mixed type (15 cases). Myxoid matrixes (29 tumors) were formed
      mainly in the tissues of spindle cell type and were positive for Alcian blue (pH
      2.5). Cartilaginous matrixes (12 tumors) were formed in the myxoid tumor tissues.
      The morphology of atrophied neoplastic cells, which were embedded in the
      cartilage cavities, significantly differed from that of spindle cells
      proliferating in surroundings. There were reticular areas in the process of
      transitioning from myxoid to cartilaginous matrixes. Osteoid matrixes were not
      continuous with myxoid or cartilaginous matrixes, and arose as eosinophilic
      trabeculae in the dense collagenous connective tissues. A calcified bone
      trabecula was present among the osteoid trabeculae in a case. Melanin-producing
      melanocytes were proliferating in the collagenous matrixes, while amelanotic
      cells were in the osteoid matrixes. Immunohistochemistry demonstrated
      proliferating neoplastic cells as melanocytes. All cells in/out of these three
      matrixes were positive for Melan-A, S-100 protein, NSE, and vimentin. From these
      results, it is suggested that cartilage and osteoid matrixes are produced by
      dedifferentiated melanocytes.

PMID- 18057831
TI  - Effects of electroacupuncture on intraocular pressure and hemodynamic parameters
      in isoflurane anesthetized dogs.
AB  - The effects of electroacupuncture (EA) on intraocular pressure (IOP) and
      hemodynamic parameters were evaluated in isoflurane anesthetized 10 (5 males, 5
      females) normal mongrel dogs (8.1-9.8 kg, 6-8 years old). After determination of
      baseline IOP and hemodynamic parameters (cardiac index, systolic arterial
      pressure, diastolic arterial pressure, heart rate and systemic vascular
      resistance index), EA was applied at 3 acupoints (LI-4, LIV-3 and GB-37) for 20
      min. After the EA treatment, IOP was significantly decreased in the both eyes
      (p<0.05). However, there were not significant differences in hemodynamic
      parameters between those of before and after EA treatment. From these results,
      the EA treatment at LI-4, LIV-3 and GB-37 would be considered one of the valuable
      methods for the IOP treatment in dogs.

PMID- 18057832
TI  - Comparison of antibody titers in rabbits following immunization with inactivated
      influenza virus via subarachnoidal or subcutaneous route.
AB  - Rabbits were immunized with inactivated influenza virus via the subarachnoidal
      (SA) or subcutaneous (SC) route, and the antibody titers in cerebrospinal fluid
      (CSF) and serum were assayed. There were no nervous signs or morphological
      lesions related to SA immunization. In the SC group, the antibody titer was
      elevated in serum, but not elevated in CSF. In the SA group, the antibody titer
      was significantly elevated in serum and even in CSF, and their antibody titers
      were much greater than in the SC group. The present results suggest that
      intrathecal immunization is more effective than SC immunization at inducing a
      protective immune response against the transneural spread of viruses.

PMID- 18057833
TI  - Mitral stenosis with bacterial myocarditis in a cat.
AB  - An eleven-year-old female Japanese mongrel cat was referred to the Tottori
      University Veterinary Teaching Hospital for assessment of acute paresis and
      dyspnea. Two-dimensional echocardiography showed a hydropericardium. The mitral
      valve leaflets were thickened, the separation of the right and left leaflets was
      not complete. Treatments with intravenous fluids of lactate Ringer solution,
      furosemide, urokinase, antibiotics were initiated, but did not improve the
      respiratory failure. The cat died 10 days later. From pathological and
      microbiological examinations, this was an unusual case diagnosed as acquired
      mitral stenosis associated with congenital malformation of the mitral valve
      complex, and accompanied by secondary infectious myocarditis with Streptococcus
      canis.

PMID- 18057834
TI  - Expression of aquaporin water channels in the rat pituitary gland.
AB  - We investigated the expression of aquaporin (AQP) subtypes (AQP1-AQP9) in the rat
      pituitary gland by the reverse transcription-polymerase chain reaction (RT-PCR)
      and immunohistochemistry. Specific amplification by RT-PCR was observed in AQP1,
      AQP3, AQP4 and AQP5 but not in the others. AQP1 immunoreactivity was detected in
      the endothelial cells of blood vessels. No positive reaction to AQP3 was observed
      by immunohistochemistry, in spite of the detection of mRNA. AQP4 was localized in
      the supporting cells of the adenohypophysis and neurohypophysis. AQP5 was
      expressed in parts of the marginal cells in Rathke's residual pouch. These
      observations suggest that several subtypes of the AQP family are involved in
      regulation of water homeostasis in the rat pituitary gland.

PMID- 18057835
TI  - Clinical comparison of recovery from total intravenous anesthesia with propofol
      and inhalation anesthesia with isoflurane in dogs.
AB  - The characteristics of recovery from total intravenous anesthesia (TIVA) with
      propofol and inhalation anesthesia with isoflurane was clinically compared in 149
      client-owned dogs that anesthetized for surgical or diagnostic procedures. In all
      dogs, anesthesia was induced with an intravenous injection of propofol following
      premedication with acepromazine or diazepam. As a result, 58 dogs anesthetized
      with propofol-TIVA showed slower but smoother recovery than 91 dogs anesthetized
      with isoflurane anesthesia. The dogs stood at 34.5 +/- 19.3 and 27.7 +/- 17.2 min
      after propofol-TIVA and isoflurane anesthesia, respectively. Adverse effects,
      including hypersalivation, neurologic excitement (paddling, muscle
      tremor/twitching, opisthotonos) and vomiting/retching, were observed in similar
      infrequent incidences during the recovery from both anesthetic protocols.
      Propofol-TIVA is suggested to be an alternative anesthetic protocol for canine
      practice.

PMID- 18057836
TI  - A case of lymphoma developing in the rabbit cecum.
AB  - A rare lymphoma that developed in the cecum of a domestic pet rabbit (6 years
      old, male, crossbred) was examined pathologically. The tumor consisted of
      proliferating neoplastic lymphoid cells, which were strongly stained with anti
      CD79alpha monoclonal antibody. Electron microscopy revealed the tumor cells were
      composed of rough endoplasmic reticula and/or dilated rough endoplasmic reticula
      filled with moderately electron-dense material. These findings indicated the
      present case was rare digestive tract lymphoma originated from B-lymphocytic
      lineage in the cecum.

PMID- 18057837
TI  - Granulomatous nephritis and meningoencephalomyelitis caused by Halicephalobus
      gingivalis in a pony gelding.
AB  - A ten-year-old Shetland pony gelding showed low appetite, ataxia, peculiar
      swaying, clouding of consciousness, and ultimately died. At necropsy, multiple
      coalescing granulomatous foci were detected in the kidneys, and small necrotic
      lesions were found in the cerebellum. Histologic examination of the renal tissue
      sections revealed extensive granuloma, and Halicephalobus gingivalis-like
      nematodes were seen. Similar nematodes were found in the granulomatous or
      necrotic lesions of the renal lymph nodes and cerebellum, and were also
      frequently detected in cerebrospinal meningovascular lesions. Morphologic
      features together with partial ribosomal RNA gene sequences of the nematodes in
      the lesions revealed that they were H. gingivalis. The present results indicated
      that H. gingivalis caused granulomatous nephritis and meningoencephalomyelitis in
      this pony gelding.

PMID- 18057838
TI  - Molecular survey of Babesia canis in dogs in Nigeria.
AB  - An epidemiological study of Babesia canis in dogs in Nigeria was performed. Four
      hundred blood samples collected from dogs in Nigeria were investigated using
      nested PCR and sequence analysis. On nested PCR screening, nine samples (2.3%)
      produced a band corresponding to a 698-bp fragment indicative of B. canis
      infection. Sequence analysis of the PCR products identified eight samples (2.0%)
      as B. canis rossi and the ninth (0.3%) as B. canis vogeli. This is the first
      report of the prevalence of B. canis rossi and B. canis vogeli in dogs in
      Nigeria.

PMID- 18057839
TI  - A canine case of necrotizing meningoencephalitis for long-term observation:
      clinical and MRI findings.
AB  - A 3-year-old female pug presented with general seizure following a partial
      seizure. During the remaining 48 months till death, the dog showed various
      neurological signs such as disturbance of consciousness, myoclonus and various
      types of partial seizure after each occurrence of the seizure clusters, and the
      dog eventually exhibited inability to stand and dementia. Magnetic resonance
      imaging findings revealed atrophy of the brain over the course of the disease. On
      histopathological analysis, the dog was diagnosed with necrotizing
      meningoencephalitis. This case of a canine necrotizing meningoencephalitis
      observed over the long term is valuable.

PMID- 18057840
TI  - Construction of a recombinant plasmid as reaction control in routine PCR for
      detection of contagious equine metritis (CEM-PCR).
AB  - Contagious equine metritis (CEM) is a highly contagious bacterial venereal
      disease of horses caused by Taylorella equigenitalis. CEM-PCR is a semi-nested
      PCR method for detecting this bacterium. Although this technique is regarded as a
      sensitive diagnostic method for CEM, there are risks of it generating false
      positive and false negative results. In this study, we constructed a recombinant
      plasmid (CEM-POS) as reaction control to assure adequate PCR reaction and prevent
      false positive results caused by contamination of the reaction control in routine
      CEM-PCR examinations. CEM-POS was constructed by insertion of rpoB fragments from
      Rhodococcus equi into CEM-1P, which is a recombinant plasmid that includes a T.
      equigenitalis-specific sequence region. In CEM-PCR, the size of the PCR product
      from CEM-POS was clearly different from the true positive PCR product. In
      addition, CEM-POS retained high stability under convenient storage conditions of
      4 degrees C. These results suggest CEM-POS to be a useful tool as a reaction
      control in routine CEM-PCR examinations.

PMID- 18057841
TI  - Putative host cell receptor for fowl adenovirus detected in gizzard.
AB  - This work was done to identify a fowl adenovirus (FAV) binding protein in the
      gizzard, a known target organ for certain strains of FAV serotype 1. By using a
      virus overlay protein binding assay (VOPBA), a putative FAV binding protein of
      approximately 200 kDa expressed in the gizzard was detected.

PMID- 18057842
TI  - Characterization of CD34+ cells from canine umbilical cord blood, bone marrow
      leukocytes, and peripheral blood by flow cytometric analysis.
AB  - Characterization of CD34+ cells in canine bone marrow, umbilical cord blood, and
      peripheral blood was performed by flow cytometric analysis. The ratio of
      CD34+CD45hi cells, which are absent in human blood, was high in the CD34+ cell
      fraction, but 98% of these was suggested B-cells. The remaining CD34+CD45lo cells
      may comprise canine hematopoietic progenitor cells, and these cells accounted for
      0.23 +/- 0.07% of the fraction in cord blood, 0.30 +/- 0.07% in bone marrow, and
      0.02 +/- 0.01% in peripheral blood.

PMID- 18057843
TI  - Changes of multi-drug resistance pattern in Salmonella enterica subspecies
      enterica serovar typhimurium isolates from food-producing animals in Japan.
AB  - A total of 153 isolates of Salmonella Typhimurium derived from food-producing
      animals in Japan between 2002 and 2005 were investigated for antimicrobial
      resistance and phage types related to definitive phage type 104 (DT104). The
      predominant resistance type was resistance to ampicillin, dihydrostreptomycin,
      kanamycin, and oxytetracycline in bovine (45.2%, 48/104) and resistance to
      dihydrostreptomycin and oxytetracycline in porcine isolates (58.7%, 27/48). DT104
      related phage type was found in 32 of 104 bovine isolates, two of 48 porcine
      isolates, and one of eight isolates from poultry, showing that the proportion of
      the phage type in S. Typhimurium isolates from cattle and pigs significantly
      (P<0.01) decreased from 71.9% and 31.4% in 1999-2001 to 30.8% and 4.1% in 2002
      2005, respectively.

PMID- 18057844
TI  - [Presence and future of nutrition support team in Japan].

PMID- 18057845
TI  - [The relationship between nutrition and upper gastrointestinal diseases].

PMID- 18057846
TI  - [Nutritional therapy for Crohn's disease].

PMID- 18057847
TI  - [Nutritional management for liver disease].

PMID- 18057848
TI  - [Nutrition therapy for patients with chronic pancreatitis].

PMID- 18057849
TI  - [A case of Epstein-Barr virus (EBV) associated remnant gastric carcinoma arising
      7 years after distal gastrectomy for EBV associated gastric carcinoma].
AB  - A 52-year-old man undergoing distal gastrectomy for gastric cancer in July 1998
      was found to have a 0-IIa type gastric tumor near EC junction in January 2005.
      Histological examination showed the tumor was moderately differentiated
      adenocarcinoma. As the tumor was diagnosed as mucosal cancer, endoscopic mucosal
      dissection was performed. But pathological findings showed the depth of cancer
      cell invasion into deep submucosal layer. Then total resection of remnant stomach
      was performed. Both tumors were diagnosed as EBV-associated carcinoma. It is
      speculated that the mucosa changing after initial operation would give risk to a
      new occurrence of EBV-associated remnant gastric carcinoma. And then follow up
      after operation is important. Although some cases of EBV-associated remnant
      gastric carcinoma is found for short period after the primary surgery, our case
      second primary cancer was found 7 year after primary surgery. Long term follow-up
      by Endoscopy seems to be important.

PMID- 18057850
TI  - [Crohn's ileocolitis with initially superimposed cytomegalovirus infection,
      resembling intestinal tuberculosis].
AB  - We describe a case of 41-year-old Japanese man with Crohn's ileocolitis and
      cytomegalovirus infection, confirmed by histology of ileal ulcers. Although his
      colonoscopic and radiological features resembled those of intestinal
      tuberculosis, granulomas of typical Crohn's disease were evident on histology of
      biopsy specimens taken from the duodenum and colon. The lesions remain unchanged
      even after 1.5 years by oral administration of salazosulphapyridine 3g daily.

PMID- 18057852
TI  - [A case of adult neuroblastoma arising in the retroperitoneum following a poorly
      aggressive course].
AB  - A 69-year-old man complaining of enlarged cervical mass, appetite loss and lower
      abdominal pain was found to have abdominal tumors in heaps forming a large mass
      around the retroperitoneum. The biopsy specimen in the cervical mass showed
      undifferentiated carcinoma with neuroendocrine feature. This malignancy followed
      a poorly aggressive course and caused death in only 24 hospital days. The disease
      was diagnosed as undifferentiated neuroblastoma arising in the retroperitoneum by
      autopsy with appropriate immunohistochemical studies. Adult neuroblastoma in the
      peritoneum is rare and our case showed a aggressive behavior and unfortunate
      outcome.

PMID- 18057851
TI  - [Complete response to treatment with hepatic arterial infusion of cisplatin
      powder (IA-call) in a case of hepatocellular carcinoma with multiple lung
      metastases].
AB  - A 74-year-old woman was admitted to our hospital to treat her hepatocellular
      carcinoma (stage IVB) with multiple lung metastases. She was treated with 3 times
      of hepatic arterial infusion of cisplatin powder (IA-call). After the treatment,
      liver mass and lung tumors were disappeared and high levels of tumor markers (AFP
      and PIVKA-II) were markedly decreased. These data revealed that a complete
      response (CR) was obtained for her. She has still been maintained in CR for 2
      years since the first treatment.

PMID- 18057853
TI  - [Late-onset type ornitine transcarbamirase deficiency (OTCD) with fulminant onset
      following a fatal prognosis].
AB  - A 16-year-old man was admitted to our hospital with nausea, general fatigue, and
      consciousness disturbance along with extreme hyperammoniemia eight days after the
      onset of symptoms. Familial history and the high concentration of orotic acid in
      urine lead us to a diagnosis of OTCD. We immediately initiated intensive
      treatment such as continuous hemodiafiltration and sodium benzoate
      administration; however, the patient died twelve days after admission. Since OTCD
      is not so rare and can be found in all ages, it should be considered fundamental
      for evaluation of hyperammoniemia. This case suggested that for a better
      prognosis of OTCD patients it is very important to prevent such an onset, and to
      make an as early as possible diagnosis and start to treatment.

PMID- 18057854
TI  - [A case of intrahepatic splenosis].
AB  - When a 32-year-old man was 18 a traffic accident caused splenic rupture, for
      which he underwent splenectomy, complicated postoperatively by hepatitis. As part
      of routine follow-up with his family doctor for chronic hepatitis C, a hepatic
      tumor was detected on plain abdominal computed tomography (CT), and he was
      admitted to our hospital for further investigation and treatment. Based on the
      results of abdominal dynamic CT, abdominal magnetic resonance imaging(MRI),
      abdominal angiography, CT during hepatic arteriography (CTHA) and CT during
      arterial portography (CTAP), we performed a laparotomy for suspected
      hepatocellular carcinoma. The operative findings were a 40 mm dark purple-brown
      nodule on the surface of the S7 segment of the liver, as well as multiple
      nodules, less than 20 mm in size but otherwise of similar appearance, scattered
      over the abdominal viscera and peritoneum, in particular the greater omentum. A
      hepatectomy was not performed, as we considered this to be a case of intrahepatic
      splenosis, so the abdomen was closed after a liver biopsy was taken.
      Histopathological examination of this specimen confirmed the diagnosis. As there
      have been only 19 previous reported cases of intrahepatic splenosis, we hereby
      present this valuable case with a review of the literature.

PMID- 18057855
TI  - [A case of spindle cell type anaplastic carcinoma of the body of the pancreas].
AB  - We report a resected case of small spindle cell carcinoma of the pancreas, In a
      Japanese 71-year-old woman with upper abdominal pain, a computed tomography (CT)
      showed a solid tumor 10 mm in diameter in the body of the pancreas. We perfomed
      distal pancreatectomy with splenectomy. Twenty months after the operation, the
      patient is alive without recurrence. Although the outcome of spindle cell
      carcinoma of the pancreas has been reported to be very poor, there may be hope of
      cure in the patients with small spindle cell carcinoma.

PMID- 18057856
TI  - [Diffuse large B-cell lymphoma initially manifested by massive ascites and a
      small gastric lesion, clinically mimicking primary effusion lymphoma (PEL) in the
      abdominal cavity: a case report and review of the literature on Japanese PEL
      patients].
AB  - A 50-year-old man was admitted because of increasing massive ascites. While
      lymphoma cells (diffuse large B-cell lymphoma: DLBCL) were detected in the
      ascites, pleural effusion, cerebrospinal fluid and bone marrow, no tumor masses
      other than a submucosal lymphoma lesion in the stomach only 1 cm in diameter were
      identified. The patient was treated with chemotherapy including rituximab (R-CHOP
      ESHAP) and injection of methotrexate and dexamethasone into the medullary cavity
      as well as radiation to the whole brain, and achieved complete remission 4 months
      later. The present case suggests that DLBCL can initially manifest as a form of
      effusion lymphoma with minimum solid tumor component. The distinctive clinical
      features of Japanese patients with primary effusion lymphoma are also reviewed.

PMID- 18057857
TI  - Loss of heterozygosity (LOH) on chromosomes 2q, 3p and 21q in Indian oral
      squamous cell carcinoma.
AB  - Around the world, 200,000 people a year are affected by oral cancer, and the
      incidence of this disease is 10 times higher in India than Japan, mainly due to
      the custom of chewing tobacco. Loss of heterozygosity (LOH) on the long arm of
      chromosome 2 (2q), the short arm of chromosome 3 (3p) and the long arm of
      chromosome 21 (21q) are observed in several human cancers. We identified novel
      tumor suppressor loci on these regions in primary oral squamous cell carcinomas
      (OSCCs) in Japanese. However, there has been no detailed analysis of LOH on these
      chromosomes in Indians. In the present study, we investigated LOH at 2q, 3p and
      21q using 9 microsatellite markers in 26 Indian OSCCs. LOH was detected in 25
      (96.2%) out of 26 informative samples at one or more of the loci examined. On the
      basis of the results, two commonly deleted regions were identified and a detailed
      deletion map was constructed. In the first region, a high frequency of LOH was
      observed at the D3S1007 locus (53.8%) on 3p25, which is located in the region
      neighboring the VHL (von Hippel-Lindau) gene. In the second region, LOH was
      concentrated at the D3S966 locus (50.0%) on 3p21.3, suggesting the presence of a
      putative tumor suppressor gene (TSG) associated with OSCCs. These results
      strongly suggest that there are at least two candidate TSGs located on chromosome
      3p, and that alteration in them is associated with the tumorigenesis of OSCCs.

PMID- 18057858
TI  - Estimation of optimal amount of fluoride dentifrice for adults to prevent caries
      by comparison between fluoride uptake into enamel in vitro and fluoride
      concentration in oral fluid in vivo.
AB  - Fluoride dentifrice has been accepted widely for use in caries prevention and its
      effectiveness has been confirmed. In order to enable the use of fluoride
      dentifrice effectively in daily brushing, the present study was performed to
      examine the relationship between fluoride uptake and the amount of fluoride
      dentifrice used and brushing time for adults. We examined the relationship
      between fluoride uptake into the surface layer (4-6 microm)of enamel and the
      active fluoride concentration in vitro and the relationship between the amount of
      fluoride dentifrice (1,000 ppmF) used and the fluoride concentration in oral
      fluid in vivo. It became clear that fluoride uptake into the enamel was increased
      at the concentrations of 300 ppmF or more. Fluoride uptake at 300 ppmF was
      increased for 2 min and became saturated thereafter. The results of the
      relationship between the fluoride concentration in the oral fluid and the amount
      of fluoride dentifrice used indicated that the amount of dentifrice that could
      maintain the mean fluoride concentration at 300 ppm or more for 2 min was 1.0 g
      or more. From these results, the recommended amount of fluoride dentifrice (1,000
      ppmF) is 1.0 g or more for adults.

PMID- 18057859
TI  - Study on internal structure of zygomatic bone using micro-finite element analysis
      model--differences between dentulous and edentulous dentition in Japanese
      cadavers.
AB  - The purpose of this study was to analyze changes in the internal structure of
      zygomatic bone using a micro-finite element analysis model (muFEA) and compare
      angular orientation of trabeculae against compressive force in edentulous and
      dentulous jaws. Twenty zygomatic bones from dentulous jaws and 20 zygomatic bones
      from edentulous jaws harvested from Japanese male cadavers were used. From 2
      dimensional slice images, we reconstructed 3-dimensional (3D) structure by the
      volume rendering method using micro-computed tomography (micro-CT). To analyze
      mechanical properties, all voxels were converted to muFEA models. The angle
      between the strongest direction of trabecular bone and the axial loading
      direction (angle alpha) was then determined using the muFEA models. In the 3-D
      reconstruction images, trabecular density in dentulous jaws was higher than that
      in edentulous jaws at all loci. Trabeculae in dentulous jaws showed a plate-like
      structure. The muFEA modeling revealed that the angle of the trabeculae at the
      Jugale in edentulous jaws was lower than that in dentulous jaws. This suggests
      that the internal structure of trabeculae is influenced by occlusal force in
      zygomatic bone from edentulous jaws.

PMID- 18057860
TI  - Dental care for physically or mentally challenged at public dental clinics.
AB  - Recently, local administration bureaus have established a number of dental
      clinics and centers for the physically or mentally challenged (PMC) in
      collaboration with local dental associations. The aim of this study was to
      investigate dental treatment and general supportive care for the PMC in dental
      clinics in Tokyo. A dental clinic for the PMC located in northwestern Tokyo in a
      district with a population of about 680,000 was selected for the study. The
      variables studied based on dental records included total number of patients, type
      of disability, medical history, systemic condition, age, treatment regimen and
      type of general supportive care. The largest group of new patients was under 9
      years of age. The highest total number of patients visiting the clinic belonged
      to the 60-69-year-olds group and the 70-79-year-olds group. We also investigated
      type of disability in patients treated under intravenous sedation at time of
      dental treatment. The most common condition was dementia resulting from
      Alzheimer's disease (42.74%), autism, cerebral palsy or mental retardation, in
      descending order. The percentage of patients referred from other medical
      institutions was 17.4%, including those from private dental clinics and Dental
      University Hospitals. Type of disability in patients transferred from other
      medical institutions included developmental disorders (28.2%), senile defects
      (26.9%), chronic and psychiatric diseases (44.9%). The number of patients who
      located and visited the clinic by themselves greatly exceeded the number
      transferred by request. This suggests that a permanent system should be put in
      place offering public specialized dental clinics where the PMC many obtain
      treatment.

PMID- 18057861
TI  - Age-related differences in expression of vascular endothelial growth factor by
      periodontal ligament cells in vitro.
AB  - The purpose of this study was to evaluate age-related differences in expression
      of vascular endothelial growth factor (VEGF) by periodontal ligament (PDL) cells.
      PDL cells were obtained from Wistar male rats weighing approximately 150 g each
      in the young group and 350 g each in the old group. PDL cells derived from upper
      and lower incisors were seeded in 35-mm culture dishes after primary culture. For
      cell proliferation assays, cells were detached and counted at 1, 3, 5, 7, 11 and
      14 days after culture. VEGF mRNA expression was analyzed with TaqMan. The number
      of cells in both groups increased day by day, but the rate of increase in the
      young group was higher than that in the old group. VEGF mRNA expression in the
      young group increased from 3 to 14 days, but in the old group increased only
      slightly over the same time period. Expression ratios in the young group were
      higher than those in the old group, and there were significant differences
      between the young and old groups at 7 and 14 days of culture. In conclusion, the
      data revealed that PDL cells varied with age, and suggest that in view of such
      changes in cell proliferation and VEGF mRNA expression, age should be taken into
      consideration in periodontal treatment.

PMID- 18057862
TI  - Embryonic cardiac morphometry in Carnegie stages 15-23, from the Complutense
      University of Madrid Institute of Embryology Human Embryo Collection.
AB  - AIMS: We performed a morphometric study of cardiac development on human embryos
      to complement the scarce data on human embryonic cardiac morphometry and to
      attempt to establish, from these, algorithms describing cardiac growth during the
      second month of gestation. METHODS: Thirty human embryos from Carnegie stages 15
      23 were included in the study. Shrinkage and compression effects from fixation
      and inclusion in paraffin were considered in our calculations. RESULTS: Growth of
      the cardiac (whole heart) volume and volume of ventricular myocardium through the
      Carnegie stages were analysed by ANOVA. Linear correlation was used to describe
      the relationship between the ventricular myocardium and cardiac volumes.
      Comparisons of models were carried out through the R2 statistic. The relationship
      volume of ventricular myocardium versus cardiac volume is expressed by the
      equation: cardiac volume = 0.6266 + 2.4778 volume of ventricular myocardium. The
      relationship cardiac volume versus crown-rump length is expressed by the
      equation: cardiac volume = 1.3 e(0.126 CR length), where e is the base of natural
      logarithms. CONCLUSION: At a clinical level, these results can contribute towards
      the establishment of a normogram for cardiac development, useful for the design
      of strategies for early diagnosis of congenital heart disease. They can also help
      in the study of embryogenesis, for example in the discussion of ventricular
      trabeculation.

PMID- 18057863
TI  - A syringe simulation of biological controls for quality assessment of prospective
      lung volume measurements.
AB  - BACKGROUND: At present a syringe is being used for calibration of lung function
      devices, but biological controls are used to detect prospectively the variability
      and reproducibility of lung volumes measured by spirometers. Laboratory personnel
      is often used as biological control and therefore the cost for these measurements
      is substantial and may be reduced by replacement of a syringe procedure to
      increase the capacity of the laboratory to measure more patients. OBJECTIVES: To
      develop a mechanical syringe procedure for identification of instrument problems.
      METHODS: A commercial 3-liter precision syringe is used to simulate breathing
      maneuvers (inspiratory vital capacity, functional residual capacity, residual
      volume and total lung capacity) on a spirometer. Three healthy males representing
      biological controls performed spirometry, maximum expiratory flow volume and
      helium dilution forced residual capacity at bimonthly intervals for 3 years.
      Confidence intervals and interval widths are calculated for each parameter.
      Levene's test for equality of variances was used to test for significance between
      standard deviations. RESULTS: The interval width of inspiratory vital capacity,
      functional residual capacity, total lung capacity and residual volume of repeated
      measurements obtained from the syringe was significantly narrower than those of
      biological controls. In addition, almost all standard deviations from lung
      volumes obtained from the syringe were smaller and significantly different from
      those of the biological control. CONCLUSION: Our syringe procedure may replace
      biological controls for detection of variability of lung volumes. This will
      result in cost reduction and improve quality assessment of lung function devices.

PMID- 18057865
TI  - Deletion of tandem repeats causes flocculation phenotype conversion from Flo1 to
      NewFlo in Saccharomyces cerevisiae.
AB  - A gene, FLONS, conferring NewFlo-type flocculation ability in yeast was cloned.
      The 3,396-bp ORF encoded a peptide of 1,132 amino acids with high identity to
      Flo1 protein. Aligned with the FLO1 gene, two repeated regions (675 and 540 bp)
      were lost in the middle of FLONS, revealing that this gene was a derived form of
      the FLO1 gene. The missing repeated sequence contained three highly homologous
      repeat units. Although the flocculation phenotype of the transformant YTS-S with
      the FLONS gene was inhibited by both mannose and glucose, it exhibited some
      distinguished physiological characteristics from the reported typical NewFlo-type
      flocculation during detailed investigation. The deletion of repeats was suspected
      to cause conversion of the flocculation phenotype from Flo1 to NewFlo, suggesting
      that intragenic tandem repeats generated functional variability in Flo1 protein.

PMID- 18057864
TI  - Effects of neonatal handling on central noradrenergic and nitric oxidergic
      systems and reproductive parameters in female rats.
AB  - Early-life environmental events that disrupt the mother-pup relationship may
      induce profound long-lasting changes on several behavioral and neuroendocrine
      systems. The neonatal handling procedure, which involves repeated brief maternal
      separations followed by experimental manipulations, reduces sexual behavior and
      induces anovulatory estrous cycles in female rats. On the afternoon of proestrus,
      neonatally handled females show a reduced surge of luteinizing hormone (LH) and
      an increased content of gonadotropin-releasing hormone in the medial preoptic
      area (MPOA). In order to detect the possible causes for the reduced ovulation and
      sexual behavior, the present study aimed to analyze the effects of neonatal
      handling on noradrenaline (NA) and nitric oxide (NO) levels in the MPOA on the
      afternoon of proestrus. Neonatal handling reduced MHPG (NA metabolite) levels and
      MHPG/NA ratio in the MPOA, indicating decreased NAergic activity. Additionally,
      neonatal handling decreased NO levels, as measured by the metabolites (NO(x)),
      nitrite and nitrate in the same period. We may conclude that the neonatal
      handling procedure decreased activity of the NAergic and NOergic systems in the
      MPOA during proestrus, which is involved in the control of LH and FSH secretion,
      and this may possibly explain the anovulatory estrous cycles and reduced sexual
      behavior of the neonatally handled female rats.

PMID- 18057866
TI  - Effect of anagrelide on platelet coagulant function in patients with essential
      thrombocythemia.

PMID- 18057867
TI  - Reduced dose of imatinib for patients with chronic myeloid leukemia and low body
      surface area.

PMID- 18057868
TI  - Effects of renal replacement therapy on plasma lipoprotein(a) levels.
AB  - Patients with end-stage renal disease (ESRD) have significantly higher levels of
      lipoprotein(a) [Lp(a)] when compared to control populations. Elevated levels of
      Lp(a) may play a role in the high incidence of cardiovascular disease in ESRD. We
      conducted a prospective study to test the hypothesis that plasma levels of Lp(a)
      decline rapidly after renal transplantation proportional to the improvement in
      renal function, but are not affected by hemodialysis. All adults that initiated
      hemodialysis or received a renal transplant from our institution during a 10
      month period were invited to participate in the study. Lp(a) levels were obtained
      immediately prior to the initiation of renal replacement therapy. In transplant
      recipients, repeat Lp(a) measures were done at 3 days, 5 days, 1 week, 2 weeks, 3
      weeks and 4 weeks post-transplant. In hemodialysis patients, repeat Lp(a)
      measures were done after 3 months. We used a mixed effects model to analyze the
      effect of time, race and creatinine on Lp(a) after transplant. Lp(a) levels
      decreased rapidly after renal transplantation. Mean Lp(a) levels at 2 weeks were
      35.3% lower than prior to transplantation. Each reduction of 50% in creatinine
      was associated with a 10.6% reduction in Lp(a) (p < 0.001). In contrast, there
      was no significant change in Lp(a) after initiation of hemodialysis. The rapid
      decrease of Lp(a) levels after renal transplantation provides support for a
      metabolic role of the kidney in Lp(a) catabolism and suggests that the increase
      in Lp(a) seen in chronic kidney disease is due to loss of functioning renal
      tissue.

PMID- 18057869
TI  - Kidney volume associations with subclinical renal and cardiovascular disease: the
      Diabetes Heart Study.
AB  - BACKGROUND: The prognostic significance of total kidney volume (TKV) in subjects
      with type 2 diabetes mellitus (T2DM) is unknown. METHODS: One hundred and seventy
      unrelated Caucasians with T2DM underwent multidetector-row computed tomography of
      the neck, chest, and abdomen to measure calcified plaque in the coronary artery
      (CorCP), carotid artery (CarCP), and infrarenal aorta (AorCP). Spearman's rank
      correlation coefficients were used to assess associations between TKV and
      subclinical renal and cardiovascular disease. Partial correlation coefficients
      were computed to adjust for the potential confounding effects of age, sex, body
      mass index, glomerular filtration rate (GFR), diabetes duration, and hemoglobin
      A(1c). Values are expressed as mean +/- SD (median in parentheses). RESULTS: The
      study group (51% female) had a mean age of 62.9 +/- 8.5 (62.3) years, a T2DM
      duration of 11.5 +/- 6.8 (10.0) years, a urinary albumin:creatinine ratio of
      109.9 +/- 396 (17.6) mg/g, a GFR of 63.8 +/- 12.8 (63.2) ml/min, a TKV of 272.4
      +/- 69.7 (261.9) cm(3), CorCP 2,170 +/- 3,394 (653), CarCP 374 +/- 673 (104),
      AorCP 14,569 +/- 17,480 (8,370), and a carotid artery intima-media thickness of
      0.70 +/- 0.14 (0.68) mm. Adjusting for age, sex, body mass index, diabetes
      duration, GFR, and hemoglobin A(1c), the TKV was significantly associated with
      AorCP (r = 0.20, p = 0.016), but not with CorCP, CarCP, or carotid artery intima
      media thickness (all p >or= 0.25). No significant associations were detected
      between TKV and blood pressure or albuminuria. CONCLUSIONS: In Caucasians with
      T2DM, TKV and calcified atherosclerotic plaque in the infrarenal abdominal aorta
      are positively associated. Common mechanisms linking renal matrix deposition with
      aortic atherosclerosis may underlie this association and require further study.

PMID- 18057870
TI  - Central auditory impairment in unilateral diencephalic and telencephalic lesions.
AB  - The extent of perceptual impairment following unilateral lesions in the auditory
      cortex, its thalamic or callosal afferents was studied with psychoacoustic tests.
      Thresholds for the discrimination of signal frequency, intensity and duration
      were acquired under three different conditions of headphone stimulation
      ('monaural', 'interaural', and 'dichotic signal/noise tests') using the three
      alternative forced-choice procedure. The different test alternatives generated
      distinct auditory percepts, which is in accordance with the assumption of
      specific signal processing at the level of the auditory brainstem and at
      thalamocortical auditory areas. Twenty-one patients from neurology were studied
      who suffered from unilateral lesions in the auditory cortex, the auditory
      thalamus, or the acoustic radiation. Location and extent of the lesions were
      assessed by magnetic resonance imaging. Monaural tests of either ear revealed no
      deficits in auditory performance. The patients showed impaired discrimination of
      signal frequency, intensity and duration in the dichotic signal/noise tests, when
      the signals were presented to the ear contralateral and the noise ipsilateral to
      the lesion. With inverted signal and noise stimulation, however, the thresholds
      were in the range of age-matched controls. All patients were able to master the
      interaural tests, which indicates the preserved ability to lateralize sound
      sources to the left and to the right with either one of the auditory cortices
      left intact. Another 24 patients were studied who had lesions mostly close to but
      sparing the before-mentioned auditory structures. All of them showed unimpaired
      performance in all test alternatives. The results indicate the specificity of the
      dichotic signal/noise tests for the identification of unilateral lesions in
      thalamocortical auditory structures. In addition, the results also point to the
      capacity of each telencephalic hemisphere to process the full range of auditory
      lateralization from left to right.

PMID- 18057871
TI  - Cochlear implantation in 3 patients with osteogenesis imperfecta: imaging,
      surgery and programming issues.
AB  - Osteogenesis imperfecta (OI) is a heterogeneous disease of the connective tissue
      caused by a defective gene that is responsible for the production of collagen
      type I, leading to defective bone matrix and connective tissue. Hearing loss
      affects 35-60% of the patients and will progress to deafness in 2-11% of OI
      patients for whom cochlear implantation may become the only remaining treatment
      option. Three patients with OI were retrieved from the Nijmegen Cochlear Implant
      Centre's database. Most of the specific observations in ear surgery on patients
      with OI, such as brittle scutum, sclerotic thickening of the cochlea,
      hyperplastic mucosa in the middle ear and persistent bleeding, were encountered
      in these 3 patients. In case 3, with severe deformities on the CT scan,
      misplacement of the electrode array into the horizontal semicircular canal
      occurred. In all 3 cases, programming was hindered by nonauditory stimulation.
      Even after reimplantation, nonauditory sensations lead to case 3 becoming a
      nonuser. Averaged electrode voltages in case 3 were deviant in accordance with an
      abnormally conductive otic capsule. Spatial spread of neural excitation responses
      in cases 1 and 2 suggested intracochlear channel interaction for several
      electrodes, often in combination with facial nerve stimulation (FNS). In case 1,
      the estimated pitch of the electrodes that caused FNS varied consistently.
      Despite the electrophysiological changes, after 1-year follow-up, open set
      phoneme scores of 81% and 78% were reached in cases 1 and 2, respectively. When
      aware and prepared for the specific changes of the temporal bone in OI, cochlear
      implantation can be a safe and feasible procedure. Preoperative imaging is
      recommended to be fully informed on the morphology of the petrosal bone. In case
      of severe deformities on the CT scan, during counseling the possibility of
      misplacement should be mentioned. Rehabilitation is often hindered by FNS
      requiring frequent refitting.

PMID- 18057872
TI  - Effects of round window dexamethasone on residual hearing in a Guinea pig model
      of cochlear implantation.
AB  - To study electric acoustic stimulation, we have developed a model of guinea pig
      cochlear implantation via a cochleostomy. Thirty minutes prior to implantation, a
      hyaluronic acid/carboxymethylcellulose bead, loaded with either dexamethasone or
      normal saline, was placed upon the round window membrane. Animals that did not
      receive beads acted as controls. Pure-tone auditory brainstem response thresholds
      were estimated before and after electrode insertion, and 1 and 4 weeks later.
      Selected cochlear histology was performed. RESULTS: Dexamethasone could be
      detected in the cochlea for 24 h after cochlear implantation. Thresholds were
      elevated across frequencies in all animals immediately after surgery. These
      thresholds recovered completely at and below 2 kHz, and partially at higher
      frequencies by 1 week after implantation. At 32 kHz, but not the lower
      frequencies, the presence of dexamethasone had a significant protective effect
      upon hearing, which increased in magnitude over time. The protection was greatest
      in difficult implantations where an intractable resistance to electrode insertion
      was met. There was a persistent foreign body reaction at the site of implantation
      of saline-treated implanted ears but not in the dexamethasone-treated implanted
      ears. CONCLUSION: Short-term preoperative delivery of dexamethasone through the
      round window can protect residual hearing during cochlear implantation,
      especially during technically difficult surgery.

PMID- 18057873
TI  - Augmented ototoxic effect of cisplatin in heterozygotes of the German waltzing
      guinea pig.
AB  - It has previously been demonstrated that the carriers of the German waltzing
      guinea pig are less susceptible to noise trauma. To explore whether this
      represents a general resistance to inner ear trauma, carriers of the German
      waltzing guinea pig were exposed to the ototoxic agent cisplatin. Two doses of
      cisplatin were injected intravenously into anesthetized carriers and weight
      matched control animals. Prior to and 96 h after the injections hearing
      thresholds were established by recording the auditory brainstem responses at 3.5,
      7, 14, and 28 kHz. The cochleae were harvested to estimate hair cell loss and to
      analyze total platinum content. The carriers of the German waltzing guinea pig
      strain suffered from a more pronounced cisplatin-induced hearing loss compared to
      the control animals. The results suggest that mechanisms responsible for the
      protection against acoustic stress do not provide any protection against
      cisplatin in carriers of the German waltzing guinea pig.

PMID- 18057874
TI  - The benefits of combining acoustic and electric stimulation for the recognition
      of speech, voice and melodies.
AB  - Fifteen patients fit with a cochlear implant in one ear and a hearing aid in the
      other ear were presented with tests of speech and melody recognition and voice
      discrimination under conditions of electric (E) stimulation, acoustic (A)
      stimulation and combined electric and acoustic stimulation (EAS). When acoustic
      information was added to electrically stimulated information performance
      increased by 17-23 percentage points on tests of word and sentence recognition in
      quiet and sentence recognition in noise. On average, the EAS patients achieved
      higher scores on CNC words than patients fit with a unilateral cochlear implant.
      While the best EAS patients did not outperform the best patients fit with a
      unilateral cochlear implant, proportionally more EAS patients achieved very high
      scores on tests of speech recognition than unilateral cochlear implant patients.

PMID- 18057875
TI  - Neuro-otological findings in patients with migraine- and nonmigraine-related
      dizziness.
AB  - This study presents the neuro-otological findings of 523 patients attending a
      tertiary vestibular clinic with migraine- and nonmigraine-related dizziness.
      Subjects were categorized into one of 4 groups, definite migrainous vertigo,
      probable migrainous vertigo, vestibular disorder coexisting with migraine and
      nonmigraine-related dizziness. No notable relationship was found between the
      numbers of abnormal findings between the groups for the majority of the neuro
      otological tests. However, there was a significant trend in emetic response to
      caloric testing. The definite migrainous vertigo group were at least 4 times more
      likely to be nauseous to caloric testing than any other migraine category. This
      difference was independent of the magnitude of caloric responses between the
      emetic migraine groups. While further investigation is required, this study has
      potentially identified that nauseous/emetic response to caloric stimulation may
      be a distinguishing factor between migrainous vertigo and other vestibular
      disorders including those with a coexisting history of migraine.

PMID- 18057876
TI  - Regional citrate anticoagulation for single-needle hemodialysis: a prospective
      clinical study.
AB  - AIM: Regional citrate anticoagulation protocol for single-needle hemodialysis was
      tested prospectively for safety and efficacy. METHODS: 15 chronic dialysis
      patients at risk of bleeding were included. 4% trisodium citrate (200 ml/h),
      calcium-free dialysate and 1 mol/l calcium chloride (7 ml/h) were used. After
      dialysis the antithrombotic effect in the circuit was assessed visually (grade 5,
      no clotting, to 1, total occlusion) and serum citrate was measured. RESULTS: Of
      32 dialyses performed, 94% were uneventful and in 2 cases (6%) there was severe
      (ionized calcium < or = 0.8 mmol/l) but asymptomatic hypocalcemia. Mean
      anticoagulation score after dialysis was 4.8 +/- 0.7 for the arterial bubble
      trap, 4.6 +/- 0.8 for the dialyzer and 4.8 +/- 0.7 for the venous bubble trap.
      Serum citrate after dialysis was 158 +/- 60 micromol/l. CONCLUSION: Regional
      citrate anticoagulation in single-needle dialysis is safe and efficient.

PMID- 18057877
TI  - Association of human platelet alloantigen 1 through 5 polymorphisms with ischemic
      stroke.
AB  - Polymorphisms in human platelet alloantigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2
      (GPIb/IX), HPA-4 (GPIIIa) and HPA-5 (GPIa/IIa) were investigated in 216 stroke
      patients and 318 matched control subjects. HPA genotyping was done by the
      polymerase chain reaction method using sequence-specific primers. Higher
      frequencies of the HPA-1 a/b (p < 0.001) and HPA-5 a/b (p < 0.001) allele,
      together with HPA-1 b/b, HPA-5 a/b and HPA-5 b/b genotypes were seen in patients,
      which was confirmed by regression analysis after controlling for a number of
      confounding variables. Furthermore, HPA-1 b/b and HPA-5 b/b were significantly
      associated with the extent of neurological symptoms, and with the recurrence of
      stroke. Both susceptible (1a/ b -2a/a-3a/ b -4a/a-5a/ b ) and protective (1a/a
      2a/a-3a/a-4a/a-5a/a; 1a/a-2a/a-3a/ b -4a/a-5a/a; 1a/ b -2a/a-3a/a-4a/a-5a/a; 1a/
      b -2a/a-3a/ b -4a/a-5a/a) HPA genotypes were identified. This is the first
      evidence demonstrating differential association of the common 5 HPA gene variants
      with stroke, with HPA-1b and HPA-5b representing strong genetic risk factors.

PMID- 18057878
TI  - Risk of fractures after stroke.
AB  - BACKGROUND: The aim of this study was to determine the risk of fractures after
      stroke/transient ischemic attack (TIA) in relatively young patients. METHODS:
      Administrative claims data were identified for patients aged 18 years and older
      hospitalized for stroke/TIA from 1997 to 2005 using ICD-9 codes. Fractures after
      stroke/TIA were identified for the same time period. RESULTS: The median age was
      56 years. Females represented 47%. There were 411 ischemic strokes, 195 TIAs and
      36 intracerebral hemorrhages, as well as 46 fractures in 41 individuals. The risk
      of fracture after stroke/TIA was 1.2% at 30 days and 3.1% at 1 year. There was no
      significant difference in survival free from fracture between ischemic stroke and
      TIA cases (p = 0.8489). CONCLUSIONS: Patients with stroke/TIA, including men and
      younger patients, appear to be at risk for bone fractures.

PMID- 18057879
TI  - The cortical involvement of territorial infarcts as a risk factor for stroke
      related seizures.
AB  - BACKGROUND: The cortical involvement of territorial infarcts is considered to be
      a significant risk factor for the development of early- as well as late-onset
      seizures. However, it is not known which cortical regions are more susceptible to
      the development of stroke-related seizures. PATIENTS AND METHODS: In this
      retrospective study of 687 patients with territorial infarcts, 184 with stroke
      related seizures were compared to 503 without seizures. The extent and the
      location of the infarcts were determined by computed tomography (CT) scans and/or
      magnetic resonance imaging (MRI) scans of the brain. The infarcts of the seizure
      and the non-seizure group were compared on digital cerebral vascular maps by
      superimposing the CT and/or MRI slices. RESULTS: In patients with late-onset
      seizures, the infarcts were significantly more frequent in the temporal and
      parietal branches of the middle cerebral artery in comparison to the non-seizure
      group. In patients with early-onset seizures and in those with seizures due to a
      recurrent stroke, the territory of the temporal and occipital branches of the
      middle cerebral artery was the predilection side of the infarcts. Generalized
      tonic-clonic seizures occurred mainly in cases of infarction in the deep
      territory of the middle cerebral and of the anterior choroidal artery. Status
      epilepticus was significantly correlated with infarcts in the posterior temporal
      region. CONCLUSION: Some infarct regions are the sides of predilection for stroke
      related seizures according to their type and their onset-time.

PMID- 18057880
TI  - The effect of anticonvulsant drugs on the fibrinolytic activity of tissue
      plasminogen activator.
AB  - BACKGROUND AND PURPOSE: Several anticonvulsant drugs have been found to be
      neuroprotective in preclinical models of stroke, and such drugs may possibly be
      given in combination with other stroke treatments such as recombinant tissue
      plasminogen activator (rt-PA). The goal of this study was to test for potential
      interactions between rt-PA and selected anticonvulsants. METHODS: A
      spectrophotomeric assay was used to monitor the lysis of fibrin clots in the
      presence of rt-PA and the drugs levetiracetam, valproic acid, phenytoin and
      phenobarbital. RESULTS: The drugs tested were found to have no effect on either
      the rate or total amount of lysis induced by rt-PA. CONCLUSIONS: Although further
      studies are required in order to explore the effects of these drugs in stroke
      patients, the results suggest that co-administration of rt-PA and anticonvulsant
      drugs may be safe and viable.

PMID- 18057881
TI  - The additive effects of the active component of grapefruit juice (naringenin) and
      antiarrhythmic drugs on HERG inhibition.
AB  - BACKGROUND: Grapefruit juice causes significant QT prolongation in healthy
      volunteers and naringenin has been identified as the most potent human ether-a-go
      go-related gene (HERG) channel blocker among several dietary flavonoids. The
      interaction between naringenin and I(Kr)-blocking antiarrhythmic drugs has not
      been studied. We evaluated the effect of combining naringenin with I(Kr)
      inhibiting antiarrhythmic drugs on cardiac I(Kr). METHODS AND RESULTS: I(Kr)
      current was studied by using HERG expressed in Xenopus oocytes, and the two
      electrode voltage clamp technique was employed. Antiarrhythmic drugs (azimilide,
      amiodarone, dofetilide and quinidine) were tested. Experiments were performed at
      room temperature. Naringenin blocked HERG current dose dependently with an IC(50)
      of 173.3 +/- 3.1 microM. Naringenin 100 microM alone inhibited HERG current by 31
      +/- 6%, and this inhibitory effect was increased with coadministration of 1 or 10
      microM antiarrhythmic drugs. When 100 microM naringenin was added to
      antiarrhythmic drugs, greater HERG inhibition was demonstrated, compared to the
      current inhibition caused by antiarrhythmic drugs alone. Addition of naringenin
      significantly increased current inhibition (p < 0.05). CONCLUSIONS: There is an
      additive inhibitory effect on HERG current when naringenin is combined with I(Kr)
      blocking antiarrhythmic drugs. This additive HERG inhibition could pose an
      increased risk of arrhythmias by increasing repolarization delay and possible
      repolarization heterogeneity.

PMID- 18057882
TI  - Myocardial contractile response to increasing doses of dobutamine in patients
      with reperfused acute myocardial infarction by cardiac magnetic resonance
      imaging.
AB  - BACKGROUND: Cardiac magnetic resonance imaging uses contractile response to
      dobutamine (DCMR) and delayed contrast enhancement (DE) to assess myocardial
      viability. However, early after acute myocardial infarction (AMI) the optimal
      dose of dobutamine is unclear. METHODS: In patients early after reperfused AMI,
      DCMR at 5, 10 and 20 microg*kg(-1)*min(-1) and measurement of DE was performed.
      On three short-axis slices 18 segments were graded as no DE, DE <50% and DE
      >or=50%. Thickening (systolic-diastolic wall thickness) and contractile reserve
      (max. thickening - rest) were determined. Segments were classified dysfunctional
      if thickening was >2 SD below normal or <2 mm. RESULTS: Forty-nine patients
      participated. In segments with no DE, thickening increased continuously but
      contractile reserve was low (0.9 +/- 3.2 mm) and dysfunctional segments were
      unchanged (rest: 13.1% vs. 20 microg: 14.8%). In segments with DE, contractile
      reserve was high (1.4 +/- 3.0 mm and 1.5 +/- 3.0 mm) and dysfunctional segments
      decreased from rest to 20 microg (50 vs. 24.8% and 79.9 vs. 43.2%). Between 5 and
      10 microg no change of thickening and of dysfunctional segments occurred.
      CONCLUSION: Early after AMI, DCMR demonstrated no diagnostic benefit in segments
      with no DE. In segments with DE, higher dose of dobutamine can provide additional
      information on contractile reserve and dysfunctional segments.

PMID- 18057883
TI  - The effects of external counter pulsation therapy on circulating endothelial
      progenitor cells in patients with angina pectoris.
AB  - OBJECTIVES: External counter pulsation therapy (ECPT) offers symptomatic relief
      and improves ischemia in patients with refractory angina pectoris. We aimed to
      determine the effects of ECPT on circulating endothelial progenitor cells (EPCs).
      METHODS: We prospectively studied 25 patients with angina pectoris treated with
      ECPT (n = 15) or receiving standard care (n = 10). The number of EPCs positive
      for CD34 and kinase insert domain receptor (KDR) was determined by flow cytometry
      and the number of colony-forming units (CFUs) was assessed in a 7-day culture,
      before ECPT and after 9 weeks. RESULTS: ECPT improved anginal score from a median
      of 3.0 to 2.0 (p < 0.001). Concomitantly, ECPT increased EPC number from a median
      of 10.2 to 17.8/10(5) mononuclear cells (p < 0.05), and CFUs from 3.5 to 11.0 (p
      = 0.01). Flow-mediated dilatation was improved by ECPT from 7.4 to 12.2% (p <
      0.001) and correlated with EPC-CFUs (r = 0.461, p = 0.027). The levels of
      asymmetric dimethylarginine were reduced by ECPT from 0.70 to 0.60 micromol/l (p
      < 0.01). In contrast, the same parameters did not change in the control group,
      before and after follow-up. CONCLUSIONS: The present pilot study shows, for the
      first time, that ECPT is associated with increased number and colony-forming
      capacity of circulating EPCs.

PMID- 18057884
TI  - Simvastatin inhibits C-reactive protein-induced pro-inflammatory changes in
      endothelial cells by decreasing mevalonate pathway products.
AB  - OBJECTIVES: The effects of HMG-CoA reductase inhibitors on C-reactive protein
      (CRP)-induced pro-inflammatory changes in endothelial cells remain unclear. We
      tested the hypothesis that simvastatin inhibited CRP-induced pro-inflammatory
      changes in endothelial cells by decreasing mevalonate pathway products. METHODS:
      Human umbilical vein endothelial cells were incubated with CRP and measurement of
      CD32, nuclear factor kappaB (NF-kappaB) activation, vascular cell adhesion
      molecule-1 expression and monocyte adhesion assay were performed. The effects of
      simvastatin, siRNA against CD32 (siCD32) and mevalonate pathway products were
      also examined. RESULTS: Pre-treatment with simvastatin significantly attenuated
      the CRP-induced CD32 expression and NF-kappaB activation in human umbilical vein
      endothelial cells. Simvastatin also decreased CRP-induced vascular cell adhesion
      molecule-1 expression and reduced monocyte adhesion on endothelial cells. The
      inhibitory effects of simvastatin were significantly reversed by adding
      mevalonate and geranylgeranyl pyrophosphate (GGPP), but not by adding farnesyl
      pyrophosphate. Pre-treatment with siCD32 also decreased CRP-induced CD32
      expression and inhibitor of kappaB degradation. However, neither mevalonate nor
      GGPP reversed the effects of siCD32. CONCLUSIONS: CRP-induced CD32 expression and
      NF-kappaB activation were attenuated by simvastatin. A decrease in mevalonate and
      subsequent GGPP contributes to the inhibitory effects of simvastatin. These
      findings may provide an explanation of using statins on patients with high serum
      CRP levels.

PMID- 18057885
TI  - Cells of primarily extravascular origin in neointima formation following stent
      implantation: coordinated expression of endothelial progenitor, dendritic and
      neural crest-derived cells.
AB  - OBJECTIVES: In-stent restenosis due to neointima formation is a major limitation
      following stent implantation. Recently, several studies reported mobilization of
      primarily extravascular cells to the arterial sites after balloon angioplasty.
      Therefore, the goal of the present study was to assess the coordinated neointimal
      expression of endothelial progenitor, dendritic and neural crest-derived cells
      after stent implantation. METHODS: Male minipigs underwent stent implantation in
      abdominal aortic segments. Animals were sacrificed at 1, 7, 14, 30, 60 or 90
      days. Cross sections of the injured vessels were obtained for
      immunohistochemistry using specific antibodies for the detection of endothelial
      progenitor (CD133), dendritic (S100) and neural crest-derived cells (GFAP), as
      well as monocytes/macrophages (CD14) and T lymphocytes (CD3). RESULTS: As a key
      finding, frequency of CD133, S100, GFAP, CD14 and CD3 (18.5 +/- 3.6, 14.9 +/-
      1.8, 10.6 +/- 1.1, 40.2 +/- 8.3 and 5.0 +/- 0.6%, respectively) in neointima was
      maximal at day 7. With ongoing neointima enlargement, expression of these cells
      decreased. In advanced neointima, labeled cells were predominantly localized at
      luminal and stented sites. Media showed almost no immunoreactivity of the markers
      studied, whereas adventitial zones of neovascularization revealed some signals.
      CONCLUSIONS: Endothelial progenitor, dendritic, neural crest-derived and
      inflammatory cells are consistently recruited into arterial neointima, mostly at
      early time points after stent implantation.

PMID- 18057886
TI  - Ivabradine as an alternative therapeutic trial in the therapy of inappropriate
      sinus tachycardia: a case report.
AB  - Inappropriate sinus tachycardia is a disease which is relatively rarely found and
      sometimes difficult to treat. Up to now it has been mostly treated with a beta
      blocker or verapamil. If this did not work sinus node modulation was considered.
      Since the relatively new selective IF-stream blocker ivabradine has been approved
      for the therapy of chronic stable angina pectoris, a new therapeutic option is
      available. As ivabradine is well tolerated and only few side effects are known,
      it may become a new therapeutic step between medication and the invasive sinus
      node modulation. We report the case of a young female patient with inappropriate
      sinus tachycardia where a sustained therapeutic success was achieved with
      ivabradine medication as an alternative therapeutic trial after various
      ineffective medications.

PMID- 18057887
TI  - Extracellular acidification and hyperkalemia induce changes in HERG inhibition by
      ibutilide.
AB  - BACKGROUND: A high incidence of proarrhythmia has been reported with ibutilide,
      especially in patients with underlying heart diseases. Our previous studies have
      shown that extracellular acidosis and hyperkalemia attenuate the HERG-inhibitory
      effect of proarrhythmic drugs, e.g. quinidine, but have little impact on the less
      proarrhythmic drug amiodarone. We hypothesized that ibutilide would behave like
      quinidine in the presence of extracellular acidosis and hyperkalemia. METHODS AND
      RESULTS: HERG was expressed on Xenopus oocytes, and the two-electrode voltage
      clamp technique was employed. Our results showed that ibutilide was a potent HERG
      inhibitor. When extracellular solution contained 5 mM KCl and pH was 7.4, the
      IC(50) of ibutilide was 0.9 +/- 0.1 microM. The inhibitory effect of ibutilide
      was attenuated when extracellular pH decreased to 6.2. There was a significant
      difference in current inhibition by ibutilide at pH 7.4 versus pH 6.2 (p < 0.01).
      When the extracellular potassium concentration was increased from 5 to 10 mM,
      ibutilide produced less current inhibition, and the IC(50) was increased to 2.0
      +/- 0.1 microM. CONCLUSION: Extracellular acidosis and hyperkalemia attenuate the
      HERG-inhibitory effect of ibutilide. The differences in HERG inhibition between
      acidic and hyperkalemic regions compared to normal regions in the myocardium may
      result in heterogeneity in repolarization, which may contribute to the
      proarrhythmic toxicity of ibutilide.

PMID- 18057888
TI  - Interventricular mechanical dyssynchrony determines abnormal heightening of
      plasma N-terminal probrain natriuretic peptide level in symptomatic
      bradyarrhythmia patients with chronic dual-chamber vs. single-chamber atrial
      pacing.
AB  - OBJECTIVE: Debates about adverse effects of ventricular- vs. atrial-based pacing
      have never ended, especially regarding cardiovascular outcomes in common
      pacemaker populations. METHODS: To investigate the contribution of right
      ventricular apical pacing to the left ventricular negative remodeling, we
      measured the inter- and intraventricular mechanical dyssynchrony by
      echocardiography as well as plasma N-terminal pro-brain natriuretic peptide (NT
      proBNP) level in 116 consecutive patients of symptomatic bradyarrhythmias
      including sinus node dysfunction (SND) in 80 and atrioventricular block in 36.
      Dual-chamber rate-modulated pacing (DDDR) pacemakers were implanted in 76
      patients (SND, 40), and single-chamber ventricular rate-modulated pacing (AAIR)
      pacemakers in 40 (all SND). Clinical manifestations were retrospectively
      correlated. RESULTS: After 3.5 years of pacing, DDDR pacemaker patients
      demonstrated higher plasma NT-proBNP concentration (503 +/- 111 pg/ml) than AAIR
      patients (194 +/- 42 pg/ml, p = 0.002) despite similar cardiovascular function at
      baseline. Multivariate regression analysis revealed that the only predictor of
      the highest quartile of plasma NT-proBNP, i.e. >or=386 pg/ml, was the
      interventricular contraction time difference (p = 0.01). Reprogramming to
      minimize ventricular pacing percentage in 8 patients of SND caused parallel
      reduction of plasma NT-proBNP. CONCLUSION: Interventricular mechanical
      dyssynchrony, imposed mostly by right ventricular apical pacing, could lead to
      abnormal heightening of plasma NT-proBNP concentration after chronic DDDR pacing
      in common pacemaker patients with normal baseline left ventricular function.

PMID- 18057889
TI  - Functional recovery of chronic ischemic myocardium after surgical
      revascularization correlates with magnitude of oxidative metabolism.
AB  - BACKGROUND: The purpose of this study was to validate myocardial microdialysis
      measurements in patients after myocardial infarction with or without associated
      postoperative functional recovery in order to develop a highly sensitive tool for
      real-time in vivo detection of microcellular disorder during cardiac operations.
      METHODS: In 20 patients undergoing coronary artery bypass grafting, microdialysis
      catheters were implanted into scar or hibernating segments detected by means of
      magnetic resonance imaging, and into a vital area of the right ventricle
      (control). Myocardial glucose, lactate and pyruvate were analyzed
      perioperatively. Myocardial ethanol washout was measured as a sign of recovered
      local blood flow. RESULTS: After surgical revascularization, improvement of wall
      motion was found in all hibernating segments compared to the scar segments
      paralleling an increased glucose delivery to the tissue and increased myocardial
      tissue flow. The myocardial glucose/lactate ratio and pyruvate also showed
      significantly higher values. Microdialytic measurements of the viable segments
      were comparable with those of the right ventricle. CONCLUSIONS: Our results
      indicate that microdialysis measurements parallel magnetic resonance imaging
      findings in patients with revascularization of chronic ischemic myocardium with
      dyskinetic segments. The metabolism of those segments is characterized by a
      significantly increased tissue flow, an increased utilization of glucose and a
      better oxidative nutrition.

PMID- 18057890
TI  - Impaired exercise capacity in diabetic patients after coronary bypass surgery:
      effects of diastolic and endothelial function.
AB  - OBJECTIVES: The aims of this study were to clarify the influence of cardiac
      diastolic and peripheral vascular function on the exercise capacity of patients
      with coronary bypass surgery (CABG) and diabetes mellitus (DM) by tissue Doppler
      imaging (TDI) and flow-mediated vasodilatation (FMD), and to investigate
      interrelations between exercise capacity and LV diastolic function, endothelial
      function and biochemical parameters. METHODS: We analyzed the exercise capacity,
      TDI at the mitral annulus and FMD in 51 uncomplicated first-time CABG survivors
      (23 DM) at an average interval of 21.6 +/- 12.2 months after surgery. RESULTS:
      Diabetics had lower E', A', VO(2)peak, (a-v)O(2) difference, and higher E/E'
      ratios (p < 0.05) than non-DM patients, but not FMD (p = 0.17). The A and E/E'
      ratios correlated negatively with VO(2)peak after age adjustment (r = -0.336, p =
      0.024). In addition, HbA(1c), and triglyceride also correlated negatively with
      VO(2)peak (r = -0.377, -0.307, respectively, p < 0.05). CONCLUSIONS: Diabetics
      after CABG had more advanced diastolic dysfunction and oxygen extraction
      impairment than non-DM. It suggests these factors could contribute to lower
      exercise capacity, risk of developing heart failure despite preserved systolic
      function and poorer long-term survival of diabetic patients after CABG.

PMID- 18057891
TI  - Homocysteine, cystatin C and N-terminal-pro brain natriuretic Peptide. Vascular
      risk markers in elderly patients with mental illness.
AB  - BACKGROUND: There is increasing evidence that vascular disease contributes to
      cognitive impairment and dementia. Clarification of the role of vascular risk
      factors in dementia is important because most are modifiable, in contrast to
      other risk factors such as age and genetics. METHODS: In 451 patients with mental
      illness we have investigated three biochemical markers related to vascular
      disease, total plasma homocysteine (tHcy), cystatin C, and N-terminal-pro brain
      natriuretic peptide (NT-proBNP), and their association with vascular disease,
      diagnoses, and brain imaging findings (CT). RESULTS: Plasma tHcy, serum cystatin
      C, and serum NT-proBNP showed significantly increased frequencies of elevated
      levels in patients with vascular disease, in patients with a pathological CT
      finding indicating cerebrovascular disease, and in patients above 75 years of
      age. CONCLUSION: It is possible that the control of conventional vascular risk
      factors and therapy could be guided by the level of plasma tHcy, serum cystatin
      C, and serum NT-proBNP. Patients with an elevation of any of these three
      parameters could be selected for a lower target level of risk factors such as
      blood pressure, hyperlipidemia etc. than conventional target levels.

PMID- 18057892
TI  - Management of complicated choledochal cysts.
AB  - OBJECTIVES: The presentation of choledochal cysts (CDCs) is altered by
      complications such as acute severe cholangitis, hepatolithiasis, spontaneous
      perforation, portal hypertension, pancreatitis, malignancy of the biliary tract
      and previous surgery in the form of internal drainage of the cyst. The management
      and the outcome of such complicated cysts differ from that of an uncomplicated
      CDC. This presentation is an analysis of our experience with complicated CDCs.
      PATIENTS AND METHODS: One hundred and forty-four patients with CDCs were managed
      at a tertiary level referral hospital in North India, between January 1989 and
      June 2004. Thirty-three (23%) CDCs were associated with complicating factors:
      severe cholangitis requiring a biliary drainage procedure prior to definitive
      operative procedure (n = 11), spontaneous perforation (n = 3), hepatolithiasis (n
      = 6), acute cholecystitis (n = 1), recurrent acute pancreatitis (n = 1), chronic
      pancreatitis (n = 1), gastric outlet obstruction (n = 1), portal hypertension (n
      = 6), biliary tract malignancy (n = 4) and previous internal drainage of the cyst
      (n = 5). Five patients had more than one complication. The management outcome of
      complicated CDCs was compared with that of uncomplicated CDCs. RESULTS:
      Complicated CDCs were significantly more common with type IV-A anatomy.
      Endoscopic, percutaneous or external surgical biliary drainage procedure was
      performed in 14 complicated CDCs prior to cyst excision. Desired definitive
      surgical procedure could be performed in 26/33 (79%) patients with complicated
      CDCs as compared to 107/111 (96%) patients with uncomplicated CDCs. Four (12%)
      patients with complicated CDCs had early postoperative complications as compared
      to 9/111 (8%) patients with uncomplicated CDCs. During a median follow-up of 13
      months (2 months to 8 years), 2 patients with complicated CDCs died due to
      advanced secondary biliary cirrhosis and advanced gall bladder cancer,
      respectively. Six patients reported complications. Of the 6 patients, 3 required
      reoperation for a strictured hepaticojejunostomy (n = 2) and hepatolithiasis (n =
      1). In contrast, there was no disease-related mortality and only 1 out of 111
      patients with uncomplicated cysts had a complication during follow-up.
      CONCLUSION: Complicated CDCs merit a carefully planned management strategy
      including percutaneous, endoscopic and surgical procedures. The management may
      have to be staged. The outcome depends on the nature of complication and the
      management strategy adopted.

PMID- 18057893
TI  - Strategy for the surgical management of insulinomas: analysis of 52 cases.
AB  - AIM: The goal of this retrospective study was to analyze the strategy for the
      surgical management of insulinomas. METHODS: From May 2000 to October 2006, the
      medical records of 52 patients with insulinomas were retrospectively studied.
      RESULTS: All tumors were localized precisely by imaging techniques combined with
      intraoperative palpation. Forty-eight patients with benign lesions underwent
      surgical treatment: 41 patients open and 7 patients laparoscopic procedures. Four
      patients with malignant insulinomas underwent tumor resection; 3 of them
      underwent metastatic lesion and/or lymph node dissection. There were no
      discrepancies regarding operation time, blood loss, and complication rate between
      open enucleation and laparoscopic surgery. The mean hospital stay was 11.8 +/-
      3.4 days after laparoscopic surgery, shorter than the 17.0 +/- 6.0 days after the
      open approach. Twenty-two complications occurred in 17 patients (32%) following
      resection. On follow-up, 86% of the patients were free from symptoms, and
      surgical cure was achieved in 95% of the patients with benign insulinomas.
      CONCLUSIONS: The choice of the surgical strategy for the treatment of pancreatic
      insulinomas depends on size and location of the tumor and the risk of malignancy.
      The optimal surgical procedure is key to prevent postoperative complications. The
      laparoscopic approach is safe and feasible for patients with benign tumors
      located in body or tail of the pancreas.

PMID- 18057894
TI  - Presentation, management and outcome of acute sigmoid diverticulitis requiring
      hospitalization.
AB  - AIM: This study was conducted to assess the presentation, management, and
      outcomes of patients with acute sigmoid diverticulitis requiring hospitalization.
      METHODS: From 1986 to 2005, the medical records of 265 patients treated for acute
      sigmoid diverticulitis requiring hospitalization were retrospectively analyzed.
      Data were collected with regard to patient's demographics, clinical
      characteristics, presentations of acute diverticulitis, treatment, morbidity, and
      mortality. RESULTS: Only 47 patients (17.7%) had a previous diverticulitis
      episode. Of the 265 patients, 166 (62.6%) were managed without operation, and 99
      (37.4%) underwent surgery. Overall and major morbidity in the whole series were
      30.2 (80/265) and 15.5% (40/265), respectively; whereas among the patients with
      surgical management, were 72.7 (72/99), and 35.3% (35/99), respectively. Overall
      and postoperative mortality rates were 2.6 (7/265) and 6.1% (6/99), respectively.
      Older age, steroid use, perforation, and co-morbidities were significantly
      associated with unfavorable outcomes. CONCLUSIONS: It was concluded that surgery
      for acute sigmoid diverticulitis requiring hospitalization carries important
      morbidity and mortality. To achieve improvements in outcome, a selective
      therapeutic approach should be considered, choosing the best surgical procedure
      for each complication of diverticular disease.

PMID- 18057895
TI  - Retrieval of an ingested toothbrush in a 16-year-old girl.

PMID- 18057896
TI  - Observations on concussion. A review.
AB  - The word 'concussion' has several meanings and applications that are
      controversial. This paper attempts to trace the historical origins and evolution
      of the descriptive classifications of concussive head injuries. It is suggested
      that head injuries should be described on the available evidence of the severity
      and duration of altered consciousness, traumatic amnesia and, when present, the
      variably associated neurological, physiological and imaging signs. The word
      concussion reflects an overenthusiastic trend in medical labelling. Since our
      understanding of types of brain injury and their symptoms and sequelae has
      advanced, the term should be abandoned.

PMID- 18057897
TI  - Incidence of status epilepticus in southern Europe: a population study in the
      health district of Ferrara, Italy.
AB  - BACKGROUND: The epidemiologic features of status epilepticus (SE) are still in
      the course of definition. METHODS: We carried out an intensive survey of multiple
      sources of case material in the resident population of the health district of
      Ferrara, Italy, in 2003. Information was collected on age, gender, duration,
      seizure type and etiology of SE. RESULTS: The age- adjusted annual incidence rate
      of SE was 27.2/100,000 (95% CI = 19.4-36.9) and it was higher in men
      (41.7/100,000, 95% CI = 26.9-61.7) than in women (12.3/100,000, 95% CI = 6.9
      20.4). The incidence was higher in the elderly (older than 60 years,
      39.2/100,000) than in younger adults in the age group 20-59 years (14.7/100,000).
      The age-specific incidence showed a bimodal distribution peaking in the youngest
      (0-4 years) and in the oldest age group (75+ years). Cerebrovascular disease was
      the most frequent etiologic factor (45%). Epilepsy had previously been diagnosed
      in 40% of the patients. The case fatality was 5%. CONCLUSIONS: The study found a
      higher incidence of SE than that expected on the basis of the previous European
      studies suggesting that the risk of SE in southern Europe is higher and more
      similar to that estimated in population studies in the United States. The case
      fatality was lower than that reported in previous South-European population
      studies despite the similar clinical features of the patients. Indirect evidence
      suggests that several factors related to the SE management could have positively
      influenced the outcome.

PMID- 18057898
TI  - Complete versus partial lateral sinus thrombosis: a pathophysiological
      hypothesis.
AB  - BACKGROUND/AIM: The lateral sinus (LS) is composed of the transverse sinus (TS)
      and sigmoid sinus (SiS). METHODS: We studied the clinical pattern of complete or
      isolated LS thrombosis in 22 consecutive patients. RESULTS: Isolated LS
      thrombosis patients had a more severe clinical presentation, and more frequent
      intracranial hemorrhages and seizures. CONCLUSION: These data suggest that
      partial involvement of the LS in the thrombotic process may cause more severe
      clinical symptoms.

PMID- 18057899
TI  - Long-term adherence to interferon beta therapy in relapsing-remitting multiple
      sclerosis.
AB  - BACKGROUND/AIMS: To assess the proportion and the reasons of drop-outs in
      relapsing-remitting multiple sclerosis patients treated with interferon-beta
      (IFNB) and the outcome of switching subjects. METHODS: Patients stopping IFNB
      were classified according to the reason of drop-out: perceived lack of efficacy
      (PLE) side effects (SE) and other reasons. Long-term adherence was described
      using the Kaplan-Meier curves. RESULTS: We evaluated 225 subjects (158 women; age
      = 36.6 +/- 9.2 years, disease duration = 8.0 +/- 6.1 years, Expanded Disability
      Status Scale score = 1.9 +/- 1.2) who received Betaferon (46), Avonex (88) and
      Rebif (91) therapy. The mean follow-up duration was 4.2 +/- 2.7 years. Forty-six
      percent of patients suspended therapy, 29% because of PLE, 15% because of SE and
      the remaining 2% due to other reasons. Twenty-five out of 33 subjects who
      suspended IFNB because of SE and 62 out of 65 patients who suspended the therapy
      due to PLE were switched to another disease-modifying drug. At the end of the
      follow-up, the majority of these patients could continue the treatment.
      CONCLUSIONS: When starting IFNB therapy in relapsing-remitting multiple
      sclerosis, a relatively high proportion of discontinuation is to be expected over
      time. Switching from a treatment to another taking into account the reasons of
      drop-out and the disease activity is a suitable option.

PMID- 18057900
TI  - Prevalence and severity of multiple-sclerosis-associated fatigue in treated and
      untreated patients.
AB  - Fatigue is one of the most frequent and most disabling symptoms in multiple
      sclerosis (MS). We investigated the possible association of the MS-related
      fatigue syndrome with the available disease-modifying therapies and the main
      disease characteristics in a cross-sectional study on 320 consecutive patients.
      The prevalence of severe fatigue (Fatigue Severity Scale score > or =5) was 50%.
      In a multivariate regression model controlling for age, disease subtype, duration
      and disability we did not find a significant association between the use of
      immunosuppressive or immunomodulatory drugs compared to no treatment (OR = 1.34,
      p = 0.38 for immunosuppressants; OR = 0.95, p = 0.85 for immune-modulating
      agents). Although all used disease-modifying agents successfully reduce disease
      activity and inflammation, they do not appear to exhibit a significant effect on
      MS-related fatigue.

PMID- 18057901
TI  - Increased prevalence of microangiopathic brain lesions among siblings of patients
      with lacunar stroke. A prospective multicenter study.
AB  - BACKGROUND: Family and twin studies suggest predisposing genetic factors in
      stroke. Lacunar infarcts represent a homogeneous phenotype, which is a
      prerequisite for genetic analyses. Applying an affected sib -pair analysis, we
      prospectively assessed the prevalence of microangiopathic brain lesions (MBL) and
      associated risk factors among siblings of patients with lacunar stroke. METHODS:
      Index patients fulfilled clinical criteria of a lacunar stroke in combination
      with a corresponding MBL on CT or MRI. Siblings were characterized as affected if
      MBL demonstrated on MRI. The prevalence of MBL was compared with population
      prevalence data extracted from other studies. RESULTS: From 784 patients
      screened, 81 index patients with lacunar stroke and 97 siblings were recruited,
      of which 42% were identified as affected. Compared with data from unselected
      historical controls and stratified by age groups, prevalence was between 2 and 5
      times higher. CONCLUSIONS: Our results indicate that genetic stroke studies are
      feasible even in subtypes of ischemic stroke. The high prevalence of MBL among
      siblings of patients with lacunar infarct might suggest a familial aggregation.
      However, due to the small sample size these results need to be interpreted with
      caution and require confirmation by planned genetic analyses.

PMID- 18057902
TI  - Toward a further elucidation: role of vertebral artery hypoplasia in migraine
      with aura.
AB  - A higher frequency of hypoplastic vertebral artery (VA) in patients with migraine
      with aura than in normal controls has been documented. However, the role of a
      hypoplastic VA in a migraine attack remains unclear. The aim of our work was to
      measure the net VA flow volume and related spectral parameters in patients with
      migraine with aura and a hypoplastic VA. From January 2005 to October 2005 we
      reviewed the records of 250 migraine outpatients (108 men and 142 women; mean age
      = 30.8 +/- 14.0 years, range = 25-55). Ninety-two patients with migraine with
      aura were selected. Among these patients, 26 had a hypoplastic VA that was
      delineated by cervical magnetic resonance angiography. We performed a case
      control study that included these 26 migrainous patients. Duplex color-coded
      ultrasonography was utilized to calculate the spectral parameters during attacks
      and headache-free periods. The net VA flow volume did not decrease during
      attacks. A reduction in the resistance index of the hypoplastic VA was noted
      during attacks in subjects who had migraine with aura. Our observation of VA
      vasomotor alteration during migraine attacks extends the understanding of the
      role of a hypoplastic VA. Vasomotor regulation of the VA could be neurogenic in
      origin. We hypothesize that VA hypoplasia contributes to migraine through complex
      neurovascular pathways rather than through its low flow volume.

PMID- 18057903
TI  - Modification of the hepatic mitochondrial proteome in response to ischemic
      preconditioning following ischemia-reperfusion injury of the rat liver.
AB  - BACKGROUND/AIM: Ischemic preconditioning (IPC) may reduce hepatic ischemia
      reperfusion (IR) injury, but efficacy of IPC on mitochondrial proteome is not
      demonstrated. We investigated how IPC modifies the mitochondrial proteome after
      IR injury. METHODS: Rats were subjected to 25 min of portal triad crossclamping
      (IR group, n = 8). In the IPC group (n = 8), 10 min of temporal portal triad
      clamping was performed before 25 min of portal clamping. Samples were obtained
      after 24 h. The mitochondrial inner-membrane potential was measured by the uptake
      of a lipophilic cationic carbocyanine probe and mitochondrial proteome was also
      investigated using 2-dimensional differential in-gel electrophoresis and liquid
      chromatography-tandem mass spectrometry. RESULTS: Mitochondrial inner-membrane
      potential and glutathione were lower and serum transaminase was higher in the IPC
      group than in the IR group. The mitochondrial precursor of aldehyde dehydrogenase
      2 and alpha-methylacyl-CoA-racemase were upregulated in the IPC group in
      comparison to the IR group. In contrast, protein disulfide-isomerase A3
      precursor, 60S acid ribosomal protein P0, carbonic anhydrase 3 and superoxide
      dismutase were significantly more downregulated in the IPC group than in the IR
      group. CONCLUSIONS: A hepatoprotective effect by IPC was not shown; however, IPC
      caused significant up- or downregulation of several mitochondrial proteins.

PMID- 18057904
TI  - The new Audiology Committee of the IALP cooperates with the WHO in the global
      work on problems of hearing-impaired people.

PMID- 18057905
TI  - Voice range profiles for tonal dialect of Min.
AB  - The influence of frequency and intensity in Min dialect on maximum vocal
      performance has not been investigated. The purposes of this study are (1) to
      investigate the physiological frequency and intensity ranges of the tonal dialect
      of Min, and (2) to compare the physiological frequency and intensity ranges of
      Min to those of nontonal languages. The subjects were 40 normal Taiwanese adults.
      All subjects were native Min speakers. The lowest frequency, the highest
      frequency, the maximum range of vowel frequency change (MRVFC), soft voice, loud
      voice, and the dynamic intensity range were obtained from voice range profiles.
      The independent t test was used to find the statistical significance of all
      frequency and intensity variables between female and male speakers in vocal range
      profiles. The results revealed that female speakers had significantly greater
      lowest frequency and highest frequency than male speakers. Male speakers had a
      significantly greater MRVFC than female speakers. Moreover, Min speakers had a
      greater MRVFC and dynamic intensity range than most of nontonal language
      speakers. The data provide an assessment tool of vocal function for Min speakers.

PMID- 18057906
TI  - Living with dysarthria: evaluation of a self-report questionnaire.
AB  - The study describes an effort to evaluate the speech difficulties as perceived by
      individuals with dysarthria. A self-report questionnaire, Living with
      Neurologically Based Speech Difficulties (Living with Dysarthria), was answered
      by 55 individuals with varying types and degrees of dysarthria. Results show that
      both type and degree of subjectively perceived communicative difficulties varied.
      Degree of communicative difficulties was not related to age, gender, diagnosis,
      disease duration or employment status in this group. Generally, the overriding
      problems were related to restrictions in communicative participation,
      possibilities to actively take part in work and studies and to express one's
      personality were particularly affected. Communication was also affected by
      emotions and by the number and familiarity of people present in communicative
      encounters. The dominating speech difficulties were related to reduced speech
      rate and a need for repetition as a consequence of misunderstandings. A
      statistically nonsignificant difference was found between the higher mean of the
      group with moderate dysarthria compared to the groups with severe and mild
      dysarthria, indicating that severity of dysarthria does not necessarily predict
      extent of perceived communicative difficulties. It is concluded that systematic
      subjective reports should always be included in the assessment of individuals
      with acquired dysarthria.

PMID- 18057907
TI  - Aerodynamic assessment of young women's voices as a function of oral
      contraceptive use.
AB  - OBJECTIVE: To examine possible differences in glottal airflow parameters
      according to oral contraceptive (OC) use. SUBJECTS AND METHODS: The participants
      included 16 women, 20-24 years of age. Eight women were taking a triphasic OC;
      the remaining 8 women were not taking any form of oral contraception (NOC). All
      participants were recorded on days 7 and 14 of their menstrual cycle. Three
      repetitions of the sustained vowel /a/ were obtained using a circumferentially
      vented respiratory face mask connected to a wide-band pressure transducer.
      Measures of peak flow, minimum flow, alternating flow, fundamental frequency
      (F(0)) and relative sound pressure level were obtained. RESULTS: A multivariate
      analysis of variance with sound pressure level as a covariate revealed no
      significant effect of day of recording upon the dependent measures. As a group,
      the OC women exhibited significantly higher F(0), peak and alternating flow rates
      compared to the NOC women. Removal of data outliers from the OC women resulted in
      similar airflow rates for both groups. CONCLUSION: The findings from this
      preliminary study did not support the use of glottal airflow measures to
      distinguish OC women from NOC women. Differences in F(0) findings may reflect
      hormonally mediated changes in laryngeal tissue and warrant further
      investigation.

PMID- 18057908
TI  - Integrating the acoustics of running speech into the pure tone audiogram: a step
      from audibility to intelligibility and disability.
AB  - BACKGROUND/AIMS: The aim of the present study is to construct a simple method for
      visualizing and quantifying the audibility of speech on the audiogram and to
      predict speech intelligibility. The proposed method involves a series of indices
      on the audiogram form reflecting the sound pressure level distribution of running
      speech. The indices that coincide with a patient's pure tone thresholds reflect
      speech audibility and give evidence of residual functional hearing capacity.
      PATIENTS AND METHODS: Two validation studies were conducted among sensorineurally
      hearing-impaired participants (n = 56 and n = 37, respectively) to investigate
      the relation with speech recognition ability and hearing disability. RESULTS: The
      potential of the new audibility indices as predictors for speech reception
      thresholds is comparable to the predictive potential of the ANSI 1968
      articulation index and the ANSI 1997 speech intelligibility index. The sum of
      indices or a weighted combination can explain considerable proportions of
      variance in speech reception results for sentences in quiet free field
      conditions. The proportions of variance that can be explained in questionnaire
      results on hearing disability are less, presumably because the threshold indices
      almost exclusively reflect message audibility and much less the psychosocial
      consequences of hearing deficits. CONCLUSION: The outcomes underpin the validity
      of the new audibility indexing system, even though the proposed method may be
      better suited for predicting relative performance across a set of conditions than
      for predicting absolute speech recognition performance.

PMID- 18057909
TI  - Clinical implementation of laryngeal high-speed videoendoscopy: challenges and
      evolution.
AB  - High-speed videoendoscopy (HSV) captures the true intracycle vibratory behavior
      of the vocal folds, which allows for overcoming the limitations of
      videostroboscopy for more accurate objective quantification methods. However, the
      commercial HSV systems have not gained widespread clinical adoption because of
      remaining technical and methodological limitations and an associated lack of
      information regarding the validity, practicality, and clinical relevance of HSV.
      The purpose of this article is to summarize the practical, technological and
      methodological challenges we have faced, to delineate the advances we have made,
      and to share our current vision of the necessary steps towards developing HSV
      into a robust tool. This tool will provide further insights into the biomechanics
      of laryngeal sound production, as well as enable more accurate functional
      assessment of the pathophysiology of voice disorders leading to refinements in
      the diagnosis and management of vocal fold pathology. The original contributions
      of this paper are the descriptions of our color high-resolution HSV integration,
      the methods for facilitative playback and HSV dynamic segmentation, and the
      ongoing efforts for implementing HSV in phonomicrosurgery, as well as the
      analysis of the challenges and prospects for the clinical implementation of HSV,
      additionally supported by references to previously reported data.

PMID- 18057910
TI  - Habituation of wild chimpanzees (Pan troglodytes) of the South Group at Tai
      Forest, Cote d'Ivoire: empirical measure of progress.
AB  - The last part of the chimpanzee (Pan troglodytes) habituation process of the Tai
      South Group was monitored over 2 years (1994-1996), during which all males and
      most of the females became habituated to observation by humans. The time needed
      (5-7 years) to habituate the community was similar to that recorded for the Tai
      North Group and is comparable to other populations studied in Africa. Variation
      emerged in habituation rate: males were habituated earlier than females, and
      among females, sexually cycling individuals were habituated faster than non
      cycling females. Such differences may be a function of both the methods used to
      find the chimpanzees and the sex of the individual. Reproductive status and
      individuality may also have influenced habituation rates by affecting the number
      of contacts required to habituate a chimpanzee to neutral humans.

PMID- 18057911
TI  - Preoperative maneuvers to avert postoperative respiratory failure in elderly
      patients.
AB  - BACKGROUND: The elderly appear particularly vulnerable to pulmonary complications
      following surgical procedures. OBJECTIVE: The purpose of this study was to
      identify and assess the merit of various maneuvers employed to mitigate
      respiratory difficulties in elderly patients undergoing surgery. RESULTS: The
      literature revealed evidence that diminishing sputum production with selective
      antibiotics and augmentation of sputum clearance with assisted coughing, postural
      drainage, and bronchodilators were deemed important. Futhermore, efforts to
      optimize nutritional status and eliminate tobacco and alcohol consumption are
      also felt to be of value in improving postsurgical outcome. CONCLUSION: One
      significant aspect of this review was the apparent posity of recent work on this
      subject despite the profound magnitude of the demise related to postsurgical
      respiratory complications in elderly patients.

PMID- 18057912
TI  - A universal combination treatment for vaginitis.
AB  - BACKGROUND: We compared a novel vaginal tablet consisting of 100 mg of
      clotrimazole and 100 mg of metronidazole ('Clo-Met') to a 100-mg clotrimazole
      tablet in the treatment of vaginitis. METHODS: A multicenter, double-blind,
      randomized controlled study. Women with vaginal discharge and diagnosed as
      suffering from vaginitis caused by Trichomonas vaginalis, bacterial vaginosis or
      Candida albicans, or any combination of the three, and who had not received
      treatment for vaginitis during the previous month, were studied. RESULTS: 165
      patients were enrolled into the study--84 into the combined therapy group, and 81
      into the clotrimazole group. In women with Candida vaginitis, Clo-Met was more
      effective than clotrimazole treatment (p < 0.012 and p < 0.05, respectively).
      CONCLUSION: A combination vaginal tablet consisting of clotrimazole and
      metronidazole is therapeutically effective in candidal vaginitis. The
      effectiveness of Clo-Met on bacterial vaginosis, T. vaginalis infection as well
      as on vaginal infections due to a combination of these microorganisms should be
      studied further.

PMID- 18057913
TI  - New preparations comprising recombinant human growth hormone: deliberations on
      the issue of biosimilars.
AB  - Manufactured recombinant human GH (rhGH) has been available for more than 25
      years. In the meantime, the GH produced by various manufacturers has been
      approved for application in replacement therapy in children and adults with GH
      deficiency or a number of disorders involving small stature in children. Until
      recently approval for each individual diagnosis was only granted after extensive
      studies on the long-term efficacy (e.g. adult height reached) and safety of the
      various products. Meanwhile, the European approving agency, the European
      Medicines Evaluation Agency (EMEA), has relinquished this restrictive stance.
      Thus, new rhGH preparations can count on gaining approval for existing
      indications even without conducting standard clinical studies of their efficacy
      and safety for each of these indications. The EMEA's reconsideration is
      apparently based on the rationale that recombinant GH can, in effect, be
      considered equivalent to the tried and tested preparations in wide use, provided
      certain specifications are met. The term 'biosimilars' was coined to denote the
      similarities between the products rather than their parity, as is the case with
      generics for instance. The higher complexity of biopharmaceuticals relates not
      only to the substances themselves but also to the manufacturing process. It is
      generally believed that modifications to a manufacturing process - which are a
      prerequisite for a patent - may cause modifications of the active substance which
      then may lead to different long-term effects. Thus, the term 'biosimilar' does
      not indicate that complex biopharmaceuticals deriving from the same substance are
      entirely identical, nor does the approval of a 'biosimilar' ensure this. The
      factual information provided here is offered towards clarification of some
      uncertainties and as a contribution towards resolving open questions relating to
      the topic of biosimilars. The final choice of product to be prescribed must be
      made by the informed, independent physician.

PMID- 18057914
TI  - Biosimilar somatropin: myths and facts.

PMID- 18057915
TI  - The past and the future of toxicology.

PMID- 18057916
TI  - Dopamine transporter mutant mice in experimental neuropharmacology.
AB  - An opportunity to perform targeted genetic manipulations in mice has provided
      another dimension for modern pharmacological research. Genetically modified mice
      have become important tools to investigate functions of previously unexplored
      proteins, define mechanism of action of new and known pharmacological drugs, and
      validate novel targets for treatment of human disorders. One of the best examples
      of such use of genetic models in experimental pharmacology represents
      investigations involving mice deficient in the gene encoding the dopamine
      transporter (DAT). The dopamine transporter tightly regulates the extracellular
      dynamics of dopamine by recapturing released neurotransmitter into the
      presynaptic terminals, and genetic deletion of this protein results in profound
      alterations in both the presynaptic homeostasis and the extracellular dynamics of
      dopamine. By using this model of severe dopaminergic dysregulation, significant
      progress has been made in defining the major target of psychotropic drugs,
      understanding the mechanisms of their action, unraveling novel signaling events
      relevant for dopaminergic transmission, and mapping neuronal pathways involved in
      dopamine-related behaviors. Furthermore, DAT mutant mice provided an opportunity
      to model in vivo conditions of extreme dopaminergic dysfunction that could be
      relevant for human disorders such as ADHD, schizophrenia, and Parkinson's disease
      and, thus, could serve as test systems for developing novel treatments for these
      and related disorders.

PMID- 18057917
TI  - The mGlu2 but not the mGlu3 receptor mediates the actions of the mGluR2/3
      agonist, LY379268, in mouse models predictive of antipsychotic activity.
AB  - RATIONALE: Group II metabotropic glutamate receptors (mGluRs) comprise the mGluR2
      and mGluR3 subtypes, the activation and modulation of which has been suggested to
      be beneficial for treating schizophrenia. Genetic association studies suggest
      limited association between mGluR2 and schizophrenia but some association between
      mGluR3 and schizophrenia. Conversely, pre-clinical studies suggest that mGluR2
      may be responsible for mediating the antipsychotic activity of mGluR2/3 agonists,
      although to date, the role of mGluR3 has not been specifically assessed.
      OBJECTIVES: The aim of this study is to use recently generated mGluR3 and mGluR2
      knockout mice to investigate which of the group II mGluRs mediates the actions of
      the mGluR2/3 agonist, LY379268, in two mouse models predictive of antipsychotic
      activity. MATERIALS AND METHODS: LY379268 (0.3-10 mg/kg SC), phencyclidine (PCP;
      1-5 mg/kg IP), and amphetamine 1-10 mg/kg IP) were assessed on locomotor activity
      and behaviour in C57Bl/6J and transgenic mice. LY379268 was then assessed on PCP
      (5 mg/kg IP)- and amphetamine (2.5 mg/kg IP)-induced hyperactivity and behaviour
      in C57Bl/6J and transgenic mice. RESULTS: PCP (5 mg/kg)-evoked hyperactivity and
      behavioural alterations, i.e. circling, falling, stereotypy and ataxia, as well
      as amphetamine (2.5 mg/kg)-evoked hyperactivity, were dose-dependently attenuated
      by LY379268 (0.3-3 mg/kg) in C57Bl/6J mice. One milligram per kilogram of
      LY379268 reversed PCP-evoked hyperactivity and behavioural alterations in wild
      type (WT) and mGluR3 knockout mice but not in mice lacking mGluR2. Similarly, 3
      mg/kg LY379268 reversed amphetamine-evoked hyperactivity in WT and mGluR3
      knockout mice but not in mice lacking mGluR2. CONCLUSION: The mGlu2 but not the
      mGlu3 receptor subtype mediates the actions of the mGluR2/3 agonist, LY379268, in
      mouse models predictive of antipsychotic activity.

PMID- 18057919
TI  - How we assure quality in teaching analytical chemistry.

PMID- 18057918
TI  - Efficacy of caffeine and modafinil in counteracting sleep deprivation in the
      marmoset monkey.
AB  - BACKGROUND AND PURPOSE: The effects of sleep deprivation are a burden in our 24-h
      society. The use of wake-promoting compounds could improve the performance in
      situations where sleep cannot be allowed. In this study, the efficacy of the wake
      promoting compounds, modafinil and caffeine, in counteracting the effects of 24-h
      sleep deprivation in the marmoset monkey were tested. As caffeine is habitually
      used, the efficacy of both compounds after short- and long-term use was
      investigated. MATERIALS AND METHODS: After a normal active day, the animals were
      kept awake and received wake-promoting compounds during the whole night. Three
      times during the sleep-deprived night, putative fatigue was assessed with an
      activity test and the vigilance and ability to execute a task was assessed with a
      hand-eye coordination (HEC) task. RESULTS: Both compounds were able to counteract
      to some extent the decline in performance. Modafinil was able to keep the
      activity at baseline performance, but performance on the HEC task was not
      improved. Caffeine was able to keep performance in the HEC task at a level just
      below daytime level but was not able to keep activity at daytime levels during
      the last part of the night. Caffeine and modafinil administration for 2 weeks
      showed a comparable effect on activity as acute use. The performance on the HEC
      task was similar after chronic caffeine and improved after chronic modafinil.
      CONCLUSION: It is therefore concluded that modafinil and caffeine were both able
      to postpone or prevent the decline in vigilance and psychomotor performance and
      increase in fatigue induced by sleep deprivation.

PMID- 18057920
TI  - The development of infant upright posture: sway less or sway differently?
AB  - Postural control is an important factor for early motor development; however,
      compared with adults, little is known about how infants control their unperturbed
      upright posture. This lack of knowledge, particularly with respect to spatial and
      temporal characteristics of infants' unperturbed independent standing, represents
      a significant gap in the understanding of human postural control and its
      development. Therefore, our first analysis offers a thorough longitudinal
      characterization of infants' quiet stance through the 9 months following the
      onset of independent walking. Second, we examined the influence of sensory
      mechanical context, light touch contact, on infants' postural control. Nine
      typically developing infants were tested monthly as they stood on a small
      pedestal either independently or with the right hand lightly touching a
      stationary contact surface. In addition to the longitudinal study design, an age
      constant sample was analyzed to verify the influence of walking experience in
      infant postural development without the confounding effect of chronological age.
      Center of pressure excursions were recorded and characterized by distance
      related, velocity, and frequency domain measures. The results indicated that,
      with increasing experience in the upright, as indexed by walk age, infants'
      postural sway exhibited shifts in rate-related characteristics toward lower
      frequency and slower, less variable velocity oscillations without changing the
      spatial characteristics of sway. Additional touch contact stabilized infants'
      postural sway as revealed by decrease in sway position variance, amplitude, and
      area as well as lower frequency and velocity. These results were confirmed by the
      age-constant analysis. Taken together, our findings suggest that instead of
      progressively reducing the sway magnitude, infants sway differently with
      increasing upright experience or with additional somatosensory information. These
      differences suggest that early development of upright stance, particularly as it
      relates to increasing postural and locomotor experience, involves a refinement of
      sensorimotor dynamics that enhances estimation of self-motion for controlling
      upright stance.

PMID- 18057921
TI  - The relation between antisaccade errors, fixation stability and prosaccade errors
      in schizophrenia.
AB  - Whether antisaccade errors in schizophrenia are due to defects in implementing
      saccadic inhibition or difficulty in generating novel responses is uncertain. We
      investigated whether antisaccade errors were related to difficulty in inhibiting
      saccades when subjects were asked to maintain steady fixation, a situation that
      does not require a novel response. We examined the ocular motor data of 15
      schizophrenia subjects and 16 healthy subjects. We assessed fixation in two
      situations: first, during the period before target onset during each saccadic
      trial, and second, during fixation trials that were interspersed with saccadic
      trials. We found that schizophrenia subjects had higher rates of fixation losses
      than control subjects in both situations. Second, both in healthy and
      schizophrenia subjects, antisaccade error rate was positively correlated with the
      frequency of fixation losses in the preparatory period of saccadic trials, but
      not with the frequency of fixation losses during fixation trials. Third,
      antisaccade errors were more likely to occur in trials with unstable fixation
      than in trials with stable fixation. Last, antisaccade error rate was also
      correlated with prosaccade error rate. We conclude that antisaccade errors are
      related to difficulties with implementing inhibitory control in the saccadic
      system. However, the finding of a correlation between the error rates for
      antisaccades and prosaccades suggests that this is not specifically concerned
      with inhibiting the automatic prosaccade, but a more general deficit in
      implementing goal-oriented behavior.

PMID- 18057922
TI  - Survival and regeneration of cutaneous and muscular afferent neurons after
      peripheral nerve injury in adult rats.
AB  - Peripheral nerve injury induces the retrograde degeneration of dorsal root
      ganglion (DRG) cells, which affects predominantly the small-diameter cutaneous
      afferent neurons. This study compares the time-course of retrograde cell death in
      cutaneous and muscular DRG cells after peripheral nerve transection as well as
      neuronal survival and axonal regeneration after primary repair or nerve grafting.
      For comparison, spinal motoneurons were also included in the study. Sural and
      medial gastrocnemius DRG neurons were retrogradely labeled with the fluorescent
      tracers Fast Blue (FB) or Fluoro-Gold (FG) from the homonymous transected nerves.
      Survival of labeled sural and gastrocnemius DRG cells was assessed at 3 days and
      1-24 weeks after axotomy. To evaluate axonal regeneration, the sciatic nerve was
      transected proximally at 1 week after FB-labeling of the sural and medial
      gastrocnemius nerves and immediately reconstructed using primary repair or
      autologous nerve grafting. Twelve weeks later, the fluorescent tracer Fluoro-Ruby
      (FR) was applied 10 mm distal to the sciatic lesion in order to double-label
      sural and gastrocnemius neurons that had regenerated across the repair site.
      Counts of labeled gastrocnemius DRG neurons did not reveal any significant
      retrograde cell death after nerve transection. In contrast, sural axotomy induced
      a delayed loss of sural DRG cells, which amounted to 22% at 4 weeks and 43-48% at
      8-24 weeks postoperatively. Proximal transection of the sciatic nerve at 1 week
      after injury to the sural or gastrocnemius nerves neither further increased
      retrograde DRG degeneration, nor did it affect survival of sural or gastrocnemius
      motoneurons. Primary repair or peripheral nerve grafting supported regeneration
      of 53-60% of the spinal motoneurons and 47-49% of the muscular DRG neurons at 13
      weeks postoperatively. In the cutaneous DRG neurons, primary repair or peripheral
      nerve grafting increased survival by 19-30% and promoted regeneration of 46-66%
      of the cells. The present results suggest that cutaneous DRG neurons are more
      sensitive to peripheral nerve injury than muscular DRG cells, but that their
      regenerative capacity does not differ from that of the latter cells. However, the
      retrograde loss of cutaneous DRG cells taking place despite immediate nerve
      repair would still limit the recovery of cutaneous sensory functions.

PMID- 18057923
TI  - Effects of the Ebbinghaus illusion on children's perception and grasping.
AB  - We investigated the development of the Ebbinghaus illusion in children's
      perception and grasping. A previous study (Hanisch et al. 2001) had reported
      negative illusion effects on 5- to 12-year-olds' grasping as compared to their
      perception. We attempted to replicate this finding and to test different
      hypotheses based on a direct influence of the context elements on the
      trajectories of the fingers which could explain this reversal of the illusion
      effects. For 5- to 7- and 9- to 11-year-olds we observed the classical illusion
      effects in perception. Illusion effects were perfectly similar for perception and
      grasping in 9- to 11-year-olds, while there was a non-significant trend toward
      smaller illusion effects in grasping for the 5- to 7-year-olds. This could be due
      to a slightly different effect of the illusion on younger children's grasping.
      However, it seems clear that there are no qualitative changes, as a reversal of
      the illusion effects in grasping of younger children. Finally, we show that our
      grasping data conform well to the motor literature for children's grasping,
      thereby strengthening our conclusions.

PMID- 18057924
TI  - Perception of hand motion direction uses a gravitational reference.
AB  - We studied possible frames of reference for kinesthetic perception of imposed
      hand motion direction in the frontal plane in ten young adult subjects with no
      history of neuromuscular disease. In one experiment, subjects were instructed to
      set unseen hand motion imposed by a motorized linear slide device parallel to the
      trunk-fixed longitudinal axis, seven visually specified axes and vertical
      (gravitational axis) while in a standard erect head/trunk posture and with
      head/trunk orientation varied. The visually specified axes were presented on a
      head-mounted display that also blocked vision of the external environment. In a
      second experiment using the same device, subjects set unseen hand motion parallel
      to vertical and to subjective oblique directions of 45 degrees clockwise (cw) and
      counter clockwise (ccw) from vertical in erect and varied head/trunk postures.
      Errors for setting hand motion to vertical and to verbally specified oblique axes
      (45 degrees cw and ccw from vertical) were lower than to the trunk longitudinal
      axis and visually specified axes. There were clear oblique effects in setting
      hand motion to visually specified axes and to subjective oblique (45 degrees cw
      and ccw) axes. When head and trunk orientation were varied, variable errors were
      higher for all axes, but remained lowest for vertical and subjective oblique
      axes. Moreover, errors for setting hand motion to all axes depended on head/trunk
      orientation. Overall, these results show that kinesthetic perception of imposed
      hand motion uses a subjective gravitational frame of reference that varies
      somewhat with head/trunk orientation.

PMID- 18057925
TI  - Capture of the eyes by relevant and irrelevant onsets.
AB  - During early visual processing the eyes can be captured by salient visual
      information in the environment. Whether a salient stimulus captures the eyes in a
      purely automatic, bottom-up fashion or whether capture is contingent on task
      demands is still under debate. In the first experiment, we manipulated the
      relevance of a salient onset distractor. The onset distractor could either be
      similar or dissimilar to the target. Error saccade latency distributions showed
      that early in time, oculomotor capture was driven purely bottom-up irrespective
      of distractor similarity. Later in time, top-down information became available
      resulting in contingent capture. In the second experiment, we manipulated the
      saliency information at the target location. A salient onset stimulus could be
      presented either at the target or at a non-target location. The latency
      distributions of error and correct saccades had a similar time-course as those
      observed in the first experiment. Initially, the distributions overlapped but
      later in time task-relevant information decelerated the oculomotor system. The
      present findings reveal the interaction between bottom-up and top-down processes
      in oculomotor behavior. We conclude that the task relevance of a salient event is
      not crucial for capture of the eyes to occur. Moreover, task-relevant information
      may integrate with saliency information to initiate saccades, but only later in
      time.

PMID- 18057926
TI  - Anticipatory smooth-pursuit eye movements in man and monkey.
AB  - A fundamental problem in the generation of goal-directed behaviour is caused by
      the inevitable latency of biological sensory systems. Behaviour which is fully
      synchronised with the triggering sensory event can only be executed if the
      occurrence of this event can be predicted based on prior information. Smooth
      pursuit eye movements are a classical and well-established example of goal
      directed behaviour. The execution of these eye movements is thought to be very
      closely linked to the processing of visual motion signals. Here, we show that
      healthy human subjects as well as trained rhesus monkeys are able to initiate
      smooth-pursuit eye movements in anticipation of a moving target. These
      anticipatory pursuit eye movements are scaled to the velocity of the expected
      target. Furthermore, we can exclude the possibility that anticipatory pursuit is
      simply an after-pursuit of the previous trial. Visually-guided pursuit is only
      marginally affected by the presence of a structured background. However, the
      presence of a structured background severely impedes the ability to perform
      anticipatory pursuit. More generally, our data provide additional evidence that
      the cognitive oculomotor repertoires of human and monkeys are similar, at least
      with respect of smooth-pursuit in the prediction of an appearing target.

PMID- 18057927
TI  - Asymmetric generalization between the arm and leg following prism-induced
      visuomotor adaptation.
AB  - We have previously shown an asymmetric generalization following a prism-induced
      visuomotor adaptation. Subjects who adapt to laterally deviating prism lenses
      during walking show a broad generalization to an arm pointing task, while
      subjects who adapt to prisms during arm pointing do not show generalization to
      walking. It is not known whether this broad generalization persists with other
      movements outside of walking or what specific features of the walking task, e.g.
      lower extremity involvement, allow it to be so broadly generalizable. In the
      current study, we tested healthy adult subjects performing one of three forms of
      prism adaptation and subsequently measured generalization. In Experiment 1 we
      tested whether a seated arm pointing prism adaptation would generalize to the
      leg. In Experiment 2 we tested whether a seated leg pointing prism adaptation
      would generalize to the arm. In Experiment 3 we tested whether standing
      influenced the extent of generalization from leg to arm. Results were surprising.
      We found a clear and consistent generalization from arm to leg, but much less so
      from leg to arm during either the seated or the standing task. These findings
      indicate that prism adaptations during arm movements are not limb-specific, as
      has been previously suggested. Further, the lack of generalization from leg to
      arm suggests that neither the adaptation of leg movements specifically, nor
      standing posture, nor the bilateral component of walking could be the salient
      feature allowing for its broad generalization across body parts.

PMID- 18057928
TI  - High prevalence of the CYP2B6 516G-->T(*6) variant and effect on the population
      pharmacokinetics of efavirenz in HIV/AIDS outpatients in Zimbabwe.
AB  - OBJECTIVE: The study sought to investigate the relationship between efavirenz
      exposure and the CYP2B6 516G-->T(*6) genotype in HIV/AIDS outpatients, using
      pharmacokinetic modelling and simulation. METHODS: Blood samples where obtained
      from 74 outpatients treated with a combination regimen including 600 mg efavirenz
      daily for a duration of at least 3 weeks at clinics in Harare, Zimbabwe. The
      subjects were genotyped for the major CYP2B6 variant, CYP2B6*6, associated with
      reduced enzyme activity, using a PCR-RFLP method. Efavirenz plasma concentrations
      were determined by HPLC-UV. Population pharmacokinetic modelling and simulation
      of the data were performed in NONMEM VI. RESULTS: A high allele frequency of the
      CYP2B6*6 allele of 49% was observed. Efavirenz plasma concentrations were above 4
      mg/L in 50% of the patients. Genotype and sex were identified as predictive
      covariates of efavirenz disposition. Pharmacokinetic parameter estimates indicate
      that a dose reduction to 400 mg efavirenz per day is possible in patients
      homozygous for the CYP2B6*6 genotype without compromising therapeutic efficacy.
      CONCLUSION: The CYP2B6*6 allele occurs at a high frequency in people of African
      origin and is associated with high efavirenz concentrations. Simulations indicate
      that an a priori 35% dose reduction in homozygous CYP2B6*6 patients would
      maintain drug exposure within the therapeutic range in this group of patients.
      Our preliminary results suggest the conduct of a prospective clinical dose
      optimization study to evaluate the utility of genotype-driven dose adjustment in
      this population.

PMID- 18057929
TI  - The anterior cerebral artery is an appropriate arterial input function for
      perfusion-CT processing in patients with acute stroke.
AB  - INTRODUCTION: Dynamic perfusion-CT (PCT) with deconvolution requires an arterial
      input function (AIF) for postprocessing. In clinical settings, the anterior
      cerebral artery (ACA) is often chosen for simplicity. The goals of this study
      were to determine how the AIF selection influences PCT results in acute stroke
      patients and whether the ACA is an appropriate default AIF. METHODS: We
      retrospectively identified consecutive patients suspected of hemispheric stroke
      of less than 48 h duration who were evaluated on admission by PCT. PCT datasets
      were postprocessed using multiple AIF, and cerebral blood volume (CBV) and flow
      (CBF), and mean transit time (MTT) values were measured in the corresponding
      territories. Results from corresponding territories in the same patients were
      compared using paired t-tests. The volumes of infarct core and tissue at risk
      obtained with different AIFs were compared to the final infarct volume. RESULTS:
      Of 113 patients who met the inclusion criteria, 55 with stroke were considered
      for analysis. The MTT values obtained with an "ischemic" AIF tended to be shorter
      (P=0.055) and the CBF values higher (P=0.108) than those obtained using a
      "nonischemic" AIF. CBV values were not influenced by the selection of the AIF. No
      statistically significant difference was observed between the size of the PCT
      infarct core (P=0.121) and tissue at risk (P=0.178), regardless of AIF selection.
      CONCLUSION: In acute stroke patients, the selection of the AIF has no
      statistically significant impact of the PCT results; standardization of the PCT
      postprocessing using the ACA as the default AIF is adequate.

PMID- 18057930
TI  - Improvement of P450(BM-3) whole-cell biocatalysis by integrating heterologous
      cofactor regeneration combining glucose facilitator and dehydrogenase in E. coli.
AB  - Escherichia coli BL21, expressing a quintuple mutant of P450(BM-3),
      oxyfunctionalizes alpha-pinene in an NADPH-dependent reaction to alpha-pinene
      oxide, verbenol, and myrtenol. We optimized the whole-cell biocatalyst by
      integrating a recombinant intracellular NADPH regeneration system through co
      expression of a glucose facilitator from Zymomonas mobilis for uptake of
      unphosphorylated glucose and a NADP(+)-dependent glucose dehydrogenase from
      Bacillus megaterium that oxidizes glucose to gluconolactone. The engineered
      strain showed a nine times higher initial alpha-pinene oxide formation rate
      corresponding to a sixfold higher yield of 20 mg g(-1) cell dry weight after 1.5
      h. The initial total product formation rate was 1,000 micromol h(-1) micromol(-1)
      P450 leading to a total of 32 mg oxidized products per gram cell of dry weight
      after 1.5 h. The physiological functioning of the heterologous cofactor
      regeneration system was illustrated by a sevenfold increased alpha-pinene oxide
      yield in the presence of glucose compared to glucose-free conditions.

PMID- 18057931
TI  - Facts and figures on CAD assessment with SPECT and PET-CT.

PMID- 18057932
TI  - Evaluation of 2'-deoxy-2'-[18F]fluoro-5-methyl-1-beta-L: -arabinofuranosyluracil
      ([18F]-L: -FMAU) as a PET imaging agent for cellular proliferation: comparison
      with [18F]-D: -FMAU and [18F]FLT.
AB  - PURPOSE: Clevudine (L: -FMAU) an un-natural analogue of thymidine, is in clinical
      trials for the treatment of hepatitis B virus (HBV). L: -FMAU is phosphorylated
      by cellular kinases such as thymidine kinase 1 and deoxycytidine kinase, and its
      triphosphate form inhibits HBV deoxyribonucleic acid synthesis. Thus, L: -FMAU,
      radiolabeled with an appropriate isotope, may be useful for positron emission
      tomography (PET) imaging of tumor proliferation. We evaluated [18F]-L-FMAU as a
      PET imaging agent in tumor-bearing mice and compared the results with those of
      two other radiotracers, [18F]-d-FMAU and [18F]-FLT. METHODS: Subcutaneous
      xenografts of the human lung cancer cell lines H441 and H3255 were established in
      mice. A micro-PET scanner was used to obtain images of the tumor-bearing animals
      with [18F]-L-FMAU, [18F]-D-FMAU, and [18F]-FLT. RESULTS: At 2 h postinjection,
      the tumor uptake (% ID/g) of 18F]-L: -FMAU, 18F]-D: -FMAU, and [18F]-FLT in the
      faster-growing H441 cells was 3.13 +/- 1.11, 7.74 +/- 1.39, and 5.10 +/- 1.45,
      respectively. The corresponding values for the slower-growing H3255 cells were
      1.38 +/- 0.81, 4.49 +/- 1.08, and 0.57 +/- 0.33. Tumor/muscle ratios of
      accumulation for [18F]-L: -FMAU, [18F]-D: -FMAU, and [18F]-FLT in H441 cells were
      4.15 +/- 1.82, 3.37 +/- 1.19, and 12.94 +/- 4.38, respectively, and the
      corresponding values in H3255 cells were 1.62 +/- 0.50, 1.96 +/- 0.74, and 1.50
      +/- 0.90. CONCLUSIONS: [18F]-L: -FMAU may be a useful agent for imaging tumor
      proliferation in fast-growing human lung cancers by PET.

PMID- 18057933
TI  - (13)N-ammonia myocardial perfusion imaging with a PET/CT scanner: impact on
      clinical decision making and cost-effectiveness.
AB  - PURPOSE: The purpose of the study is to determine the impact of 13N-ammonia
      positron emission tomography (PET) myocardial perfusion imaging (MPI) on clinical
      decision making and its cost-effectiveness. MATERIALS AND METHODS: One hundred
      consecutive patients (28 women, 72 men; mean age 60.9 +/- 12.0 years; range 24-85
      years) underwent 13N-ammonia PET scanning (and computed tomography, used only for
      attenuation correction) to assess myocardial perfusion in patients with known (n
      = 79) or suspected (n = 8) coronary artery disease (CAD), or for suspected small
      vessel disease (SVD; n = 13). Before PET, the referring physician was asked to
      determine patient treatment if PET would not be available. Four weeks later, PET
      patient management was reassessed for each patient individually. RESULTS: Before
      PET management strategies would have been: diagnostic angiography (62 of 100
      patients), diagnostic angiography and percutaneous coronary intervention (PCI; 6
      of 100), coronary artery bypass grafting (CABG; 3 of 100), transplantation (1 of
      100), or conservative medical treatment (28 of 100). After PET scanning,
      treatment strategies were altered in 78 patients leading to: diagnostic
      angiography (0 of 100), PCI (20 of 100), CABG (3 of 100), transplantation (1 of
      100), or conservative medical treatment (76 of 100). Patient management followed
      the recommendations of PET findings in 97% of the cases. Cost-effectiveness
      analysis revealed lower costs of <euro>206/patient as a result of PET scanning.
      CONCLUSION: In a population with a high prevalence of known CAD, PET is cost
      effective and has an important impact on patient management.

PMID- 18057934
TI  - Pharmacological evaluation of [123I]-CLINDE: a radioiodinated imidazopyridine-3
      acetamide for the study of peripheral benzodiazepine binding sites (PBBS).
AB  - PURPOSE: The study aims to evaluate the iodinated imidazopyridine, N',N'-diethyl
      6-Chloro-(4'-[(123)I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide ([(123)I]
      CLINDE) as a tracer for the study of peripheral benzodiazepine binding sites
      (PBBS). MATERIALS AND METHODS: In vitro studies were performed using membrane
      homogenates and sections from kidney, adrenals, and brain cortex of Sprague
      Dawley (SD) rats and incubated with [(123)I]-CLINDE. For in vivo studies, the
      rats were injected with [(123)I]-CLINDE. In competition studies, PBBS-specific
      drugs PK11195 and Ro 5-4864 and the CBR specific drug Flumazenil were injected
      before the radiotracer. RESULTS: In vitro binding studies in adrenal, kidney, and
      cortex mitochondrial membranes indicated that [(123)I]-CLINDE binds with high
      affinity to PBBS, K(d) = 12.6, 0.20, and 3.84 nM, respectively. The density of
      binding sites was 163, 5.3, and 0.34 pmol/mg protein, respectively. In vivo
      biodistribution indicated high uptake in adrenals (5.4), heart (1.5), lungs
      (1.5), kidney (1.5) %ID/g at 6 h p.i. In the central nervous system (CNS), the
      olfactory bulbs displayed the highest uptake; up to six times the activity in
      blood. Pre-administration of unlabeled CLINDE, PK11195 and Ro 5-4864 (1 mg/kg)
      reduced the uptake of [(123)I]-CLINDE by 70-55% in olfactory bulbs. In the kidney
      and heart, a reduction of 60-80% ID/g was observed, while an increase was
      observed in the adrenals requiring 10 mg/kg for significant displacement.
      Flumazenil had no effect on uptake in peripheral organs and brain. Metabolite
      analysis indicated >90% of the radioactivity in the above tissues was intact
      [(123)I]-CLINDE. CONCLUSION: [(123)I]-CLINDE displays high and selective uptake
      for the PBBS and warrants further development as a probe for imaging PBBS using
      single photon emission computed tomography (SPECT).

PMID- 18057935
TI  - Autologous versus allogeneic peptide-pulsed dendritic cells for anti-tumour
      vaccination: expression of allogeneic MHC supports activation of antigen specific
      T cells, but impairs early naive cytotoxic priming and anti-tumour therapy.
AB  - BACKGROUND: Dendritic cells (DC) pulsed with MHC class I-restricted tumour
      associated antigen (TAA) peptides have been widely tested in pre-clinical models
      and early clinical studies for their ability to prime cytotoxic T cell (CTL)
      responses. The effect of co-expression of allogeneic MHC antigens on DC
      immunogenicity has not been addressed, and has implications for the feasibility
      of clinical applications. OBJECTIVE: This study compared DC from autologous H
      2(b) or semi-allogeneic F1 H-2(bxk) mice pulsed with the H-2(b)-restricted model
      ovalbumin (OVA) peptide SIINFEKL, and compared in vitro and in vivo their ability
      to (i) activate specific OT1 cells, (ii) prime naive CTL, and (iii) protect
      against B16.OVA challenge. Peptide-pulsed autologous and allogeneic DC were also
      tested in naive human CTL priming assays. RESULTS: Semi-allogeneic DC expressed
      higher levels of co-stimulatory molecules. On pulsing with SIINFEKL they
      triggered greater proliferation of OT1 cells in vitro and in vivo, but were less
      effective at naive CTL priming and tumour protection. Autologous human DC were
      similarly more potent at naive CTL priming against the melanoma-associated TAA
      MART-1 in vitro. CONCLUSION: The expression of allogeneic MHC antigens on peptide
      pulsed DC impairs naive CTL priming and anti-tumour effects, despite effective
      TAA presentation both in vitro and in vivo.

PMID- 18057936
TI  - [Hepatocellular carcinoma in the non-cirrhotic liver].
AB  - Of hepatocellular carcinomas (HCC), 15-20% occur in the non-cirrhotic liver. All
      factors which cause HCC when liver cirrhosis (LC) is present, can also lead to
      HCC without LC. On the basis of the relative frequency, HCC can be roughly
      differentiated into 3 groups: 1) HCC, rarely occurring without cirrhosis (e.g.
      virus hepatitis, alcohol abuse). 2) HCC, frequently occurring without LC (alpha1
      antitrypsin deficiency, hemochromatosis, non-alcoholic fatty liver disease). 3)
      HCC, consistently occurring without LC (glycogen storage disease type 1,
      consumption of oral contraceptives/anabolic steroids). In groups 1 and 2 the
      level of hepatocellular toxicity necessary to reach LC is not yet achieved but
      the carcinogenic effect is already strong enough to induce HCC, possibly owing to
      the influence of additional carcinogens or host factors. In group 3, the
      carcinogenic effect is mediated by a long-standing alteration of the
      hepatocellular metabolism that is of low toxic effect and does not lead to cell
      death, but is nevertheless carcinogenic. In these cases, the initial formation of
      hepatocellular adenomas that subsequently transform into HCC is a common finding
      (adenoma-carcinoma sequence).

PMID- 18057937
TI  - A novel connection between nucleotide and carbohydrate metabolism in
      mitochondria: sugar regulation of the Arabidopsis nucleoside diphosphate kinase
      3a gene.
AB  - Sugar metabolism is intricately connected with mitochondria through the
      conversion of sugars to ATP, and through the production of carbon skeletons that
      can be used in anabolic processes. Sugar molecules also take part in signalling
      cascades. In this study we investigated the impact of sucrose on the expression
      of the Arabidopsis thaliana Nucleoside Diphosphate Kinase gene family (NDPK, EC
      2.7.4.6), focusing on NDPK3a, the product of which is located predominantly in
      mitochondria. Using quantitative PCR we show that the NDPK3a gene is subject to
      sucrose and glucose induction, while no other Arabidopsis NDPK gene are sucrose
      inducible. The induction reaches a half-maximum after about 6 hours and is stable
      for at least 48 h. Sucrose and glucose inductions were found not to be affected
      by the presence of a hexokinase inhibitor, N-acetyl-glucosamine. Furthermore,
      turanose, a sucrose analogue that is not metabolised in plant cells, did not
      induce NDPK3a gene expression. An analysis of the NDPK3a gene revealed two
      WBOXHWISO1 boxes in the promoter region, elements that have previously been
      reported to be involved in sugar signalling in barley via the SUSIBA2 protein.
      SUSIBA2 belongs to the WRKY group of transcription factors. In this study we used
      two mutants containing T-DNA insertions in WRKY-genes, AtWrky4 and AtWrky34, to
      investigate the possible involvement of WRKY transcription factors in the sugar
      induction of NDPK3a.

PMID- 18057938
TI  - Genetic transformation via somatic embryogenesis to establish herbicide-resistant
      opium poppy.
AB  - A reliable genetic transformation protocol via somatic embryogenesis has been
      developed for the production of fertile, herbicide-resistant opium poppy plants.
      Transformation was mediated by Agrobacterium tumefaciens using the pCAMBIA3301
      vector, which harbors the phosphinothricin acetyltransferase (pat) gene driven by
      a tandem repeat of the cauliflower mosaic virus (CaMV) 35S promoter and the beta
      glucuronidase (gus) structural gene driven by a single copy of the CaMV 35S
      promoter between left- and right-border sequences. Co-cultivation of explants and
      A. tumefaciens was performed in the presence of 50 microM ATP and 50 microM
      MgCl(2). Root explants pre-cultured on callus induction medium were used for
      transformation. Herbicide-resistant, proliferating callus was obtained from
      explants on a medium containing both 2,4-dichlorophenoxyacetic acid (2,4-D) and 6
      benzyladenine (BA). Globular embryogenic callus, induced by removal of the BA
      from the medium, was placed on a hormone-free medium to form somatic embryos,
      which were converted to plantlets under specific culture conditions. Plantlets
      with roots were transferred to soil, allowed to mature and set seed. Both pat and
      gus gene transcripts, and PAT and GUS enzyme activities were detected in the
      transgenic lines tested. Histochemical localization of GUS activity in T(1) opium
      poppy plants revealed transgene expression in most tissues of all plant organs.
      The protocol required 8-12 months to establish transgenic T(1) seed stocks and
      was developed using a commercial opium poppy cultivar that produces high levels
      of pharmaceutical alkaloids.

PMID- 18057939
TI  - Stress-induced expression of choline oxidase in potato plant chloroplasts confers
      enhanced tolerance to oxidative, salt, and drought stresses.
AB  - Transgenic potato plants (Solanum tuberosum L. cv. Superior) with the ability to
      synthesize glycinebetaine (GB) in chloroplasts (referred to as SC plants) were
      developed via the introduction of the bacterial choline oxidase (codA) gene under
      the control of an oxidative stress-inducible SWPA2 promoter. SC1 and SC2 plants
      were selected via the evaluation of methyl viologen (MV)-mediated oxidative
      stress tolerance, using leaf discs for further characterization. The GB contents
      in the leaves of SC1 and SC2 plants following MV treatment were found to be 0.9
      and 1.43 micromol/g fresh weight by HPLC analysis, respectively. In addition to
      reduced membrane damage after oxidative stress, the SC plants evidenced enhanced
      tolerance to NaCl and drought stress on the whole plant level. When the SC plants
      were subjected to two weeks of 150 mM NaCl stress, the photosynthetic activity of
      the SC1 and SC2 plants was attenuated by 38 and 27%, respectively, whereas that
      of non-transgenic (NT) plants was decreased by 58%. Under drought stress
      conditions, the SC plants maintained higher water contents and accumulated higher
      levels of vegetative biomass than was observed in the NT plants. These results
      indicate that stress-induced GB production in the chloroplasts of GB non
      accumulating plants may prove useful in the development of industrial transgenic
      plants with increased tolerance to a variety of environmental stresses for
      sustainable agriculture applications.

PMID- 18057940
TI  - The olfactory pathway mediates sheltering behavior of Caribbean spiny lobsters,
      Panulirus argus, to conspecific urine signals.
AB  - The "noses" of diverse taxa are organized into different subsystems whose
      functions are often not well understood. The "nose" of decapod crustaceans is
      organized into two parallel pathways that originate in different populations of
      antennular sensilla and project to specific neuropils in the brain-the
      aesthetasc/olfactory lobe pathway and the non-aesthetasc/lateral antennular
      neuropil pathway. In this study, we investigated the role of these pathways in
      mediating shelter selection of Caribbean spiny lobsters, Panulirus argus, in
      response to conspecific urine signals. We compared the behavior of ablated
      animals and intact controls. Our results show that control and non-aesthetasc
      ablated lobsters have a significant overall preference for shelters emanating
      urine over control shelters. Thus the non-aesthetasc pathway does not play a
      critical role in shelter selection. In contrast, spiny lobsters with aesthetascs
      ablated did not show a preference for either shelter, suggesting that the
      aesthetasc/olfactory pathway is important for processing social odors. Our
      results show a difference in the function of these dual chemosensory pathways in
      responding to social cues, with the aesthetasc/olfactory lobe pathway playing a
      major role. We discuss our results in the context of why the noses of many
      animals contain multiple parallel chemosensory systems.

PMID- 18057941
TI  - Effects of constant light on circadian rhythmicity in mice lacking functional cry
      genes: dissimilar from per mutants.
AB  - Mutations in each of the genes mPer1, mPer2, mCry1 and mCry2 separately cause
      deviations from the wild type circadian system. Differences between these mutant
      strains have inspired the hypothesis that the duality of circadian genes (two
      mPer and two mCry genes involved) is related to the existence of two components
      in the circadian oscillator (Daan et al., J Biol Rhythms 16:105-116, 2001). We
      tested the predictions from this theory that the circadian period (tau) lengthens
      under constant illumination (LL) in mCry1 and mPer1 mutant mice, while it
      shortens in mCry2 and mPer2 mutants. mCry1 ( -/- ) and mCry2 ( -/- ) knockout
      mice both consistently increased tau with increasing light intensity, as did wild
      type mice. With increasing illumination, rhythmicity is reduced in mCry1, mCry2
      and mPer1, but not in mPer2 deficient mice. Results for mPer mutant mice are in
      agreement with data reported on these strains earlier by Steinlechner et al. (J
      Biol Rhythms 17:202-209, 2002), and also with the predictions from the model. The
      increase in cycle length of the circadian system by light in the mCry2 deficient
      mice violates the predictions. The model is thereby rejected: the mCry genes do
      not play a differential role, although the opposite responses of mPer mutants to
      light remain consistent with a functional Evening-Morning differentiation.

PMID- 18057942
TI  - Response properties of electrosensory neurons in the lateral mesencephalic
      nucleus of the paddlefish.
AB  - Many fishes and amphibians are able to sense weak electric fields from prey
      animals or other sources. The response properties of primary afferent fibers
      innervating the electroreceptors and information processing at the level of the
      hindbrain is well investigated in a number of taxa. However, there are only a few
      studies in higher brain areas. We recorded from electrosensory neurons in the
      lateral mesencephalic nucleus (LMN) and from neurons in the dorsal octavolateral
      nucleus (DON) of the paddlefish. We stimulated with sine wave stimuli of
      different amplitudes and frequencies and with moving DC stimuli. During
      sinusoidal stimulation, DON units increased their firing rate during the negative
      cycle of the sine wave and decreased their firing rate to the positive cycle.
      Lateral mesencephalic nucleus units increased their rate for both half cycles of
      the sine wave. Lateral mesencephalic nucleus units are more sensitive than DON
      units, especially to small moving dipoles. Dorsal octavolateral nucleus units
      respond to a moving DC dipole with an increase followed by a decrease in spike
      rate or vice versa, depending on movement direction and dipole orientation.
      Lateral mesencephalic nucleus units, in contrast, increased their discharge rate
      for all stimuli. Any change in discharge rate of DON units is converted in the
      LMN to a discharge rate increase. Lateral mesencephalic nucleus units therefore
      appear to code the presence of a stimulus regardless of orientation and motion
      direction.

PMID- 18057943
TI  - Intrathecal chemotherapy for refractory disseminated medulloblastoma.
AB  - OBJECTIVE: To analyze the effect of intrathecal (IT) chemotherapy for
      disseminated medulloblastoma. MATERIALS AND METHODS: Twenty-one patients received
      IT chemotherapy using the chemotherapeutic agents of methotrexate (MTX) and
      nitrosoureas (ACNU, MCNU) including nine patients for residual leptomeningeal
      lesions after initial surgery and radiation, and 12 for a recurrence with
      leptomeningeal dissemination. Of these 21 patients, 12 received a lumbar and/or
      ventricular bolus injection of the chemotherapeutic agents, one received the
      ventriculolumbar perfusion of the agents, and eight received both the perfusion
      and bolus injection. The doses ranged from 6-7 mg/m(2) of ACNU for perfusion and
      3-3.5 mg/m(2) of ACNU, MCNU, or MTX for the bolus injection, and the cycles were
      administered from 3 to 12 times for perfusion and from 5 to 54 times for the
      bolus injection. The effects of chemotherapy were assessed by both radiological
      and cytological examinations, and the clinical symptoms were also assessed.
      Radiological and/or cytological responses were observed in 10 of 21 patients
      (47.6%), including seven cases demonstrating a complete remission. The 5-year
      overall survival rate and 5-year survival rate after dissemination were 61.5 and
      46.4%, respectively. Five patients who received a lumbar bolus injection of
      nitrosoureas experienced paraplegia and double incontinence. One patient who
      received a ventricular injection of nitrosoureas experienced truncal ataxia.
      CONCLUSION: IT chemotherapy was found to be effective in some cases with
      refractory disseminated medulloblastoma and it seems to be an appropriate
      treatment choice for leptomeningeal recurrence. However, the frequent bolus
      injections of nitrosoureas should be avoided to prevent the side effects.

PMID- 18057944
TI  - Biomechanical and functional analysis of the pins and rubbers tractions system
      for treatment of proximal interphalangeal joint fracture dislocations.
AB  - INTRODUCTION: Dynamic external fixation systems are considered as optimal devices
      for treatment of fracture dislocations of the proximal interphalangeal joint
      (PiP). The pins and rubbers traction system (PRTS) is cheap, easy to assemble and
      comfortable and allows early mobilization of the affected digit. We investigated
      the influence of different wire positions and rubber strength and provided a
      follow-up of five consecutively treated patients. METHODS: Sixteen cadaver
      fingers (dig 2-5) were included into the biomechanical study. Forces for flexion
      of the PiP joint (30 degrees, 60 degrees, and 90 degrees) were measured by
      pulling the flexor digitorum profundus tendon; width of the PiP joint was
      assessed radiologically. Measurements were obtained prior and after assembly of
      PRTS and were repeated with three different types of rubbers and two different
      positions of the retention wire (distal and proximal). The clinical part of the
      study included five patients (21-72 years) who were treated using the PRTS. Mean
      follow-up was 272 days. RESULTS: The PRTS increased flexion force of the PiP
      joint. Proximal position of the retention wire increased forces for 30 degrees
      flexion. Different rubber strengths did neither increase PiP width nor influence
      flexion forces. In the clinical part of the study total range of motion was 74
      degrees and DASH score was 10.1. Pinch grip of the affected digit was 72% of the
      unaffected side. DISCUSSION: The PRTS allows for efficient treatment of
      intraarticular fractures with PiP involvement. Although standardized positioning
      of the wires is important, proximal position of the retraction only increased
      forces for 30 degrees flexion.

PMID- 18057945
TI  - Chronic rupture of Achilles tendon: is the percutaneous suture technique
      effective?
AB  - BACKGROUND: We report the long-term results of the surgical treatment of chronic
      rupture of the Achilles tendon using percutaneous suturing under local
      anesthesia. PATIENTS AND METHODS: We operated on 22 patients with median age of
      50 years (29-72) with chronic rupture of Achilles tendon between 1991 and 2005.
      The median time from injury to surgery was 7.1 weeks (4-40). We used percutaneous
      surgical technique similar to a technique described by Ma and Griffith (1977,
      Clin Orthop Relat Res 128:247-255) and Kosanovic (1994, Arch Orthop Trauma
      Surgery 113:177-179). Eighteen (82%) patients attended the clinical review at a
      mean of 67 months (14-176). During follow up, patients were asked about pain,
      stiffness, weakness of the calf, footwear restrictions, occupation and level of
      activity before and after injury (Tegner score), influence of injury on ADL
      activities and satisfaction with treatment. The passive and active range of
      movement of the ankle and the power of isometric plantar flexion were measured,
      and the endurance test was performed. Functional assessment was performed using a
      Leppilahti clinical scoring scale and a modified Merkel score RESULTS: Complete
      healing of the tendon was achieved in 21 patients (95%). In 17 patients (77%) the
      postoperative course was complications free. There were no reruptures during the
      observation period. All were able to stand on the tiptoe of the injured leg. The
      operated leg had a mean of 87.5% of the isometric power compared with the
      uninjured leg (p = NS). On an average they could stand on toes and raise the heel
      13 times on side with the ruptured tendon. The Leppilahti scoring scale revealed
      a result that was excellent for 11 patients (62%), good for 2 (11%), fair for 5
      (28%) and no one had poor result. The average score was 83.3 (60-100). Eighty
      three percent of patients stated that the result of surgery was very good and 11%
      rated it as good. Fourteen patients (78%) returned to same level of activity at
      median 7 months after surgery. CONCLUSIONS: Our series is one of the largest to
      be reported for the treatment of chronic rupture. Our technique offers a
      considerable advantage; it is minimal invasive, easy to perform with no
      associated harvesting morbidity and increased patient acceptance. We recommend
      this technique for the treatment of chronic rupture of Achilles tendon.

PMID- 18057946
TI  - Potential risk of cartilage damage in double bundle ACL reconstruction: impact of
      knee flexion angle and portal location on the femoral PL bundle tunnel.
AB  - The aim of this study was to compare the impact of knee flexion angle and the
      level of the medial drilling portal on a potential damage to the subchondral bone
      in double bundle ACL reconstruction, drilling the femoral PL tunnel through an
      accessory medial portal. We hypothesized that a knee flexion angle of 70 degrees
      and 90 degrees or a high accessory medial portal will result in a potential
      damage to the subchondral bone of the lateral femoral condyle. In a sawbone knee
      model, the medial portal location was standardized as 0 mm above the meniscus
      (low portal) and 10 mm above the meniscus (high portal). Femoral PL bundle
      tunnels were drilled at three different knee flexion angels: 70 degrees , 90
      degrees , and 110 degrees of knee flexion. For each portal, ten specimens were
      used for every flexion angle. Drilling the PL tunnel through the high medial
      portal at a knee flexion angle of 70 degrees resulted in damage of the
      subchondral bone plate in all specimens. At 110 degrees of flexion the distance
      of the tunnel exit to the subchondral bone plate was significantly higher than at
      70 degrees of flexion for both the groups, drilling through the high and low
      medial portal (P < 0.05). Drilling through the low portal did not result in bone
      plate damage at 90 and 110 degrees of knee flexion angle. Drilling of the femoral
      PL bundle tunnel through a high medial portal at low knee flexion angles may
      damage the subchondral bone of the lateral compartment. In ACL reconstruction
      restoring the AM and PL bundle separately, high medial portal drilling should be
      avoided. We recommend drilling of the femoral PL bundle tunnel through a low
      medial portal in high knee flexion.

PMID- 18057947
TI  - Auditory steady-state responses to multiple simultaneous stimuli in children with
      functional or sensorineural hearing loss.
AB  - The goal of our study was to identify the role of auditory steady-state responses
      for hearing assessment in patients with functional hearing loss. The study design
      was to compare auditory steady-state response thresholds and standard pure-tone
      audiometry thresholds between patients with functional or sensorineural hearing
      loss. Subjects comprised 16 patients (24 ears) with functional hearing loss and
      17 patients (24 ears) with sensorineural hearing loss. Differences and
      correlations between auditory steady-state response thresholds and standard pure
      tone audiometry thresholds at 500, 1,000, 2,000 and 4,000 Hz were evaluated. In
      children with functional hearing loss, pure-tone audiometry thresholds and
      auditory steady-state response thresholds were significantly different at all
      frequencies and were not significantly correlated. In patients with sensorineural
      hearing loss, pure-tone audiometry thresholds and auditory steady-state response
      thresholds did not differ significantly at any frequencies and were significantly
      correlated. Auditory steady-state responses may have principal role in the
      assessment of auditory brainstem acuity, particularly at low frequencies in
      patients with functional hearing loss.

PMID- 18057948
TI  - Hyperplastic epithelial lesions of the vocal folds: combined use of exfoliative
      cytology and laryngostroboscopy in differential diagnosis.
AB  - The mainstay of successful tumor therapy is early detection of neoplastic tissue.
      Although exfoliative cytology has proven to be a reliable tool, its importance is
      still underestimated. Laryngostroboscopy is the most important tool for
      functional investigation in laryngological and phoniatric diagnosis. Stroboscopic
      evaluation allows early detection of infiltrative processes of the vocal folds.
      Aim of our study was to demonstrate that combination of both, exfoliative
      cytology and stroboscopy, provides a highly sensitive and easy to perform method
      in differential diagnosis of epithelial hyperplastic lesions of the vocal folds.
      In 130 patients with varying degrees of vocal fold keratosis up to glottic
      cancer, preoperative layngostroboscopy was performed. Stroboscopy was classified
      pathological in case of reduced or abolished amplitude of vocal fold vibration
      and/or reduced or abolished mucosal wave propagation. Under general anaesthesia
      histology with corresponding cytological specimens were obtained. The latter were
      classified in three groups reaching from normal (I), dysplastic (II), up to
      malignant (III) cytology. Invasive carcinoma was diagnosed in 32 cases by
      histology, corresponding malignant cytology was found in 21 specimens
      (sensitivity: 74%). By certain combination of cytology with pathological
      stroboscopy, a sensitivity of more than 97% can be achieved. Combination of
      cytology and stroboscopy allows detection of glottic cancer with a sensitivity of
      97%, in contrast to 74% as found by cytology alone. This combination can be used
      as preliminary or sorting procedure and gives the opportunity of early detection,
      as well as for follow-up examinations. For repeated biopsies can cause scars with
      consecutive voice impairment, this procedure is very smooth but nevertheless
      reliable method.

PMID- 18057949
TI  - Multiple mechanisms of chromosome movement in vertebrate cells mediated through
      the Ndc80 complex and dynein/dynactin.
AB  - Kinetochores bind microtubules laterally in a transient fashion and stably, by
      insertion of plus ends. These pathways may exist to carry out distinct tasks
      during different stages of mitosis and likely depend on distinct molecular
      mechanisms. On isolated chromosomes, we found microtubule nucleation/binding
      depended additively on both dynein/dynactin and on the Ndc80/Hec1 complex.
      Studying chromosome movement in living Xenopus cells within the simplified
      geometry of monopolar spindles, we quantified the relative contributions of
      dynein/dynactin and the Ndc80/Hec1 complex. Inhibition of dynein/dynactin alone
      had minor effects but did suppress transient, rapid, poleward movements. In
      contrast, inhibition of the Ndc80 complex blocked normal end-on attachments of
      microtubules to kinetochores resulting in persistent rapid poleward movements
      that required dynein/dynactin. In normal cells with bipolar spindles,
      dynein/dynactin activity on its own allowed attachment and rapid movement of
      chromosomes on prometaphase spindles but failed to support metaphase alignment
      and chromatid movement in anaphase. Thus, in prometaphase, dynein/dynactin likely
      mediates early transient, lateral interactions of kinetochores and microtubules.
      However, mature attachment via the Ndc80 complex is essential for metaphase
      alignment and anaphase A.

PMID- 18057950
TI  - Expression and localization of PMCA4 in rat testis and epididymis.
AB  - It has recently been shown in mice that the plasma membrane Ca(2+)-ATPase isoform
      4 (PMCA4) is essential for sperm fertilization capacity. We analyzed whether
      sperm PMCA4 is formed in the rat during spermatogenesis or is synthesized in the
      epididymis and transferred onto sperm during sperm maturation. We could show that
      PMCA4 is conserved in sperm from testis to epididymis. In testis, PMCA4 mRNA was
      restricted to spermatogonia and early spermatocytes, while the PMCA4 protein was
      detected in spermatogonia, late spermatocytes, spermatids and in epididymal
      sperm. In epididymis PMCA4 mRNA was localized in basolateral plasma membranes of
      epithelial cells of the caput, corpus and cauda epididymidis. In contrast, the
      protein was only detectable in the epithelial cells of the caput, indicating that
      PMCA4 mRNA is only translated into protein in caput epithelium. In the epididymal
      corpus and cauda, PMCA4 mRNA and protein, respectively, was localized and in
      peritubular cells. Furthermore, we detected an identical distribution of PMCA4a
      and b splice variants in rat testis, epididymal corpus and cauda. In the caput
      epididymidis, where PMCA4 is located in the epithelium splice variant 4b was more
      prominent. Further experiments have to clarify the functional importance of the
      differences in the PMCA4 distribution.

PMID- 18057951
TI  - Evaluation of medical decisions' effectiveness: a 4-year evidence-based study in
      a health care setting.
AB  - OBJECTIVES: Specific studies evaluating the effectiveness of the judgement of
      fitness for work formulated by occupational physicians (OP) are needed. The
      evaluation consists in investigating OPs' decisions by measuring their impact on
      health with specific indicators. This specific study aims at assessing, through
      outcome indicators, the effectiveness of medical decisions in 61 cases leading to
      preventive interventions. METHODS: A 3-step pre-post observational study was
      carried out in a 4-year period. About 61 clinical cases of health care workers
      were studied according to the following steps: (1) a medical examination
      resulting in an evidence-based judgement of fitness for work including
      prescriptions for an appropriate intervention, (2) the application of the
      preventive intervention, (3) a second medical examination and completion of a
      questionnaire by the workers. Two outcome measures were chosen to investigate
      changes occurred after the intervention: the first measured the perceived and the
      objective health condition, the second measured satisfaction and working
      capacity. RESULTS: Results show a statistically significant increase in subjects
      presenting a perceived (36/61; chi 2 = 44.099, P < 0.001) and an objective
      (28/61; chi 2 = 12.190, P < 0.01) improvement of health conditions after the
      intervention, together with an increased satisfaction in working conditions. An
      overall improvement of health condition was shown in 44/61 workers (72%).
      CONCLUSIONS: Decisions made on the basis of a comprehensive process founded on
      scientific evidence, searched and appraised according to the paradigm of Evidence
      Based Occupational Health, result in effective outcomes.

PMID- 18057953
TI  - Physiology-based modeling of cortical auditory evoked potentials.
AB  - Evoked potentials are the transient electrical responses caused by changes in the
      brain following stimuli. This work uses a physiology-based continuum model of
      neuronal activity in the human brain to calculate theoretical cortical auditory
      evoked potentials (CAEPs) from the model's linearized response. These are fitted
      to experimental data, allowing the fitted parameters to be related to brain
      physiology. This approach yields excellent fits to CAEP data, which can then be
      compared to fits of EEG spectra. It is shown that the differences between resting
      eyes-open EEG and standard CAEPs can be explained by changes in the physiology of
      populations of neurons in corticothalamic pathways, with notable similarities to
      certain aspects of slow-wave sleep. This pilot study demonstrates the ability of
      our model-based fitting method to provide information on the underlying
      physiology of the brain that is not available using standard methods.

PMID- 18057952
TI  - Digital blood flow and temperature responses in palmar and dorsal skin induced by
      short-term vibration exposure while grasping a vibratory handle.
AB  - OBJECTIVE: The present study was designed to examine the simultaneous responses
      in digital circulation at both palmar and dorsal skin induced by acute exposure
      to short-term vibration while grasping a vibratory handle, and also to evaluate
      the importance of measurement site for such responses. METHODS: Finger blood flow
      (FBF) and finger skin temperature (FST) were measured from the palmar (index
      finger) and dorsal (middle finger) regions of the right hand in eight male
      subjects, at rest for 5 min and while gripping the handle for 15 min. At the end
      of fifth minute during grasping of the handle, subject's hand was exposed for 5
      min to four different exposure conditions (vibration at three frequencies of
      31.5, 125 and 250 Hz with a frequency weighted rms acceleration of 5.5 m/s(2),
      and no vibration). RESULTS: During vibration exposure relative to the
      corresponding control conditions, the %change (calculated from before exposure
      mean value in gripping condition) in dorsal FBF increased substantially (P < 0.01
      0.001), and the %change for decreased palmar FST augmented significantly (P <
      0.05-0.01) in all frequencies. After vibration exposure, blood flow and skin
      temperature also remained significantly higher in dorsal finger (P < 0.05-0.005),
      and significantly lower in palmar finger (P < 0.005-0.001) at different
      frequencies comparing to the control values. Also, only vibration exposure caused
      significantly different %changes in digital circulation between palmar and dorsal
      fingers (P < 0.001). CONCLUSION: These data suggest that vibration can affect the
      digital circulation in both palmar and dorsal skin but differently. Therefore,
      while comparing the data of digital circulatory responses induced by acute
      exposure to hand-transmitted vibration recorded at palmar and dorsal sides of the
      hand, cautions are required when interpreting the results.

PMID- 18057954
TI  - Assessment of brain interactivity in the motor cortex from the concept of
      functional connectivity and spectral analysis of fMRI data.
AB  - Functional magnetic resonance imaging (fMRI) was used to assess the contributions
      of movement preparation and execution of a visuomotor task in a cerebral motor
      network. The functional connectivity of the voxel time series between brain
      regions in the frequency space was investigated by performing spectral analysis
      of fMRI time series. The regional interactivities between the two portions of the
      supplementary motor area (pre-SMA and SMA-proper) and the primary motor cortex
      (M1), defined as a seed region, were evaluated. The spectral parameter of
      coherence was used to describe a correlation structure in the frequency domain
      between two voxel-based time series and to infer the strength of the functional
      interaction within our presumed motor network of connections. The results showed
      meaningful differences of the functional interactions between the two portions of
      the SMA and the M1 area depending on the task conditions. This approach
      demonstrated the existence of a functional dissociation between the pre-SMA and
      SMA-proper subregions. We therefore conclude that spectral analysis is useful for
      identifying functional interactions of brain regions and might provide a powerful
      tool to quantify changes in connectivity profiles associated with various
      components of an experimental task.

PMID- 18057955
TI  - p53 Expression and apoptosis in liver and spleen during CO2 pneumoperitoneum.
AB  - BACKGROUNDS AND AIMS: Laparoscopic surgery techniques have been increasingly
      preferred to classic laparotomy by surgeons since 1987. However, this method has
      some important adverse effects on intra-abdominal organs. The aim of this study
      is to evaluate the effects of different pressures of CO(2) on apoptosis and p53
      expression in cells in liver and spleen. METHODS: In total, 30 male Sprague
      Dawley rats were used in the study. CO(2) was insufflated into the intra
      abdominal cavity via angiocatheter cannule by an insufflator in two different
      pressures of 10 and 20 mm Hg for 60 min. However, in the control group, only
      cannule was inserted into the intra-abdominal cavity, but no gas was insufflated.
      After 60 min, the rats were killed and laparotomy was applied. The liver and
      spleen were excised. The samples were histologically processed and
      immunohistochemistry was applied. RESULTS: All the data revealed that the number
      of apoptotic cells in liver and spleen increases in proportion to CO(2) pressure
      level. No p53 expression was detected in both organs. CONCLUSION: CO(2) pressure
      level and application time may affect on cells living in liver and spleen. High
      pressure and/or long application time may cause releasing of cytokines and
      superoxide radicals from these organs' cells, and transient or serious organ
      dysfunctions may occur.

PMID- 18057956
TI  - Adenosine receptors in rat and human pancreatic ducts stimulate chloride
      transport.
AB  - Previously, we have shown that pancreatic acini release adenosine triphosphate
      (ATP) and ATP-handling enzymes, and pancreatic ducts express various purinergic
      P2 receptors. The aim of the present study was to establish whether pancreatic
      ducts also express adenosine receptors and whether these could be involved in
      secretory processes, which involve cystic fibrosis transmembrane regulator (CFTR)
      Cl- channels or Ca2+-activated Cl- channels and H(+)/HCO(-)(3) transporters.
      Reverse transcriptase polymerase chain reaction analysis on rat pancreatic ducts
      and human duct cell adenocarcinoma lines showed that they express A1, A2A, A2B,
      and A3 receptors. Real-time PCR revealed relatively low messenger RNA levels of
      adenosine receptors compared to beta-actin; the rank order for the receptors was
      A2A>A2B>or=A3>>A1 for rat pancreas and A2B>A2A>>A3>or=A1 for duct cell lines.
      Whole-cell patch-clamp recordings on rat pancreatic ducts showed that, in about
      half of the recordings, adenosine depolarized the membrane voltage, and this was
      because of the opening of Cl- channels. Using a Cl--sensitive fluorophore and
      single-cell imaging on duct cell lines, it was found that 58% of PANC-1 cells
      responded to adenosine, whereas only 9% of CFPAC-1 cells responded. Adenosine
      elicited Ca2+ signals only in a few rat and human duct cells, which did not seem
      to correlate with Cl- signals. A2A receptors were localized in the luminal
      membranes of rat pancreatic ducts, plasma membrane of many PANC-1 cells, but only
      a few CFPAC-1 cells. Taken together, our data indicate that A2A receptors open Cl
      channels in pancreatic ducts cells with functional CFTR. We propose that
      adenosine can stimulate pancreatic secretion and, thereby, is an active player in
      the acini-to-duct signaling.

PMID- 18057957
TI  - Imaging CFTR in its native environment.
AB  - Application of atomic force microscopy (AFM) on isolated plasma membranes is a
      valuable method to study membrane proteins down to single-molecule level in their
      native environment. The cystic fibrosis transmembrane conductance regulator
      (CFTR), a protein of the adenosine triphosphate-binding cassette transporter
      superfamily, is known to play a crucial role in maintaining the salt and water
      balance on the epithelium and to influence processes such as cell volume
      regulation. A mutation in the gene encoding for CFTR results in cystic fibrosis
      (CF), a very common lethal genetic disease. Identification of CFTR within the
      cell membrane at the single-molecule level makes it feasible to visualize the
      distribution and organization of CFTR proteins within the cell membrane of
      healthy individuals and CF patients. We were able to show that human red blood
      cells have a CFTR distribution comparable to that of epithelial cells and that
      the number of CFTR in cells derived from CF patients is strongly reduced. Studies
      on CFTR-expressing oocytes disclose CFTR dynamics upon CFTR activation. We
      observed that cyclic adenosine monophosphate induces an insertion of CFTR in the
      plasma membrane and the formation of heteromeric CFTR-containing structures with
      yet unknown stoichiometry. The structure of CFTR was identified by high
      resolution scans of immunogold-labeled CFTR, revealing that CFTR forms a tail-to
      tail dimer with a central pore. In conclusion, these studies show that AFM
      experiments on isolated plasma membranes allow not only quantification and
      localization of membrane proteins but also provide insight in their dynamics at a
      single-molecule level.

PMID- 18057958
TI  - ABCB1 (P-glycoprotein) but not ABCC1 (MRP1) is downregulated in peripheral blood
      mononuclear cells of spontaneously hypertensive rats.
AB  - Although the kidney is a major target in hypertension, several studies have
      correlated important immune alterations with the development of hypertension in
      spontaneously hypertensive rats (SHR), like increased secretion of pro
      inflammatory cytokines, inflammatory infiltration in kidneys and thymic atrophy.
      Because adenosine-triphosphate-binding cassette sub-family B member 1 (ABCB1; P
      glycoprotein) and adenosine-triphosphate-binding cassette sub-family C member 1
      (ABCC1; multidrug resistance protein 1), two proteins first described in
      multidrug resistant tumors, physiologically transport several immune mediators
      and are required for the adequate functioning of the immune system, we aimed to
      measure the expression and activity of these proteins in peripheral blood
      mononuclear cells (PBMC), thymocytes, and also kidneys of normotensive Wistar
      Kyoto rats and SHR. Our results showed that ABCB1, but not ABCC1, activity was
      diminished (nearly 50%) in PBMC. Moreover, Abcb1b gene was downregulated in PBMC
      and kidney of SHR and this was not counterbalanced by an upregulation of its
      homolog Abcb1a, suggesting that the diminished activity is due to downregulation
      of the gene. No alteration was detected in ABCB1 activity in SHR thymocytes,
      indicating that this downregulation occurs after lymphocytes leave the primary
      lymphoid organs. Even though it is not known at present which parameter(s)
      is(are) responsible for this downregulation, it may contribute for the altered
      immune response observed in hypertension and to possible altered drug disposition
      in hypertensive individuals, resulting in greater drug interaction and increased
      drug toxicity.

PMID- 18057959
TI  - Dissociation of force decline from calcium decline by preload in isolated rabbit
      myocardium.
AB  - It is well known that the rate of intracellular calcium ([Ca2+]i) decline is an
      important factor governing relaxation in unloaded myocardium. However, it remains
      unclear to what extent, under near physiological conditions, the intracellular
      calcium transient amplitude and kinetics contribute to the length-dependent
      increase in force and increase in duration of relaxation. We hypothesize that
      myofilament properties rather than calcium transient decline primarily determines
      the duration of relaxation in adult mammalian myocardium. To test this
      hypothesis, we simultaneously measured force of contraction and calibrated
      [Ca2+]i transients in isolated, thin rabbit trabeculae at various lengths at 37
      degrees C. Time from peak tension to 50% relaxation (RT50(tension)) increases
      significantly with length (from 49.8+/-3.4 to 83.8+/-7.4 ms at an [Ca2+]o of 2.5
      mM), whereas time from peak calcium to 50% decline (RT50(calcium)) was not
      prolonged (from 124.8+/-5.3 to 107.7+/-11.4 ms at an [Ca2+]o of 2.5 mM). Analysis
      of variance revealed that RT50(tension) is significantly correlated with length
      (P<0.0001). At optimal length, varying the extracellular calcium concentration
      increased both developed force and calcium transient amplitude, but RT50(tension)
      remained unchanged (P=0.90), whereas intracellular calcium decline actually
      accelerated (P<0.05). Thus, an increase in muscle length will result in an
      increase in both force and duration of relaxation, whereas the latter is not
      primarily governed by the rate of [Ca2+]i decline.

PMID- 18057961
TI  - That's what task sets are for: shielding against irrelevant information.
AB  - Goal-directed behavior requires the cognitive system to distinguish between
      relevant and irrelevant information. The authors show that task sets help to
      shield the system from irrelevant information. Participants had to respond to
      eight different colored word stimuli under different instruction conditions. They
      either had to learn the stimulus-response mappings (SR condition), to use one
      task set (1 TS condition) or to use two different task sets (2 TS condition). In
      the 2 TS and the SR conditions, participants showed response repetition effects
      (interaction of color repetition x response repetition), indicating that
      participants processed the color of the words. Importantly, the 1 TS condition
      did not show such an interaction. Overall, the results provide evidence for the
      shielding function of task sets. This benefit turns into costs in classical task
      switching paradigms. From this perspective, switch costs can be interpreted as
      the consequence of successful shielding on the previous task.

PMID- 18057960
TI  - Insights into the chemical composition of Equisetum hyemale by high resolution
      Raman imaging.
AB  - Equisetaceae has been of research interest for decades, as it is one of the
      oldest living plant families, and also due to its high accumulation of silica up
      to 25% dry wt. Aspects of silica deposition, its association with other
      biomolecules, as well as the chemical composition of the outer strengthening
      tissue still remain unclear. These questions were addressed by using high
      resolution (<1 microm) Confocal Raman microscopy. Two-dimensional spectral maps
      were acquired on cross sections of Equisetum hyemale and Raman images calculated
      by integrating over the intensity of characteristic spectral regions. This
      enabled direct visualization of differences in chemical composition and
      extraction of average spectra from defined regions for detailed analyses,
      including principal component analysis (PCA) and basis analysis (partial least
      square fit based on model spectra). Accumulation of silica was imaged in the
      knobs and in a thin layer below the cuticula. In the spectrum extracted from the
      knob region as main contributions, a broad band below 500 cm(-1) attributed to
      amorphous silica, and a band at 976 cm(-1) assigned to silanol groups, were
      found. From this, we concluded that these protrusions were almost pure amorphous,
      hydrated silica. No silanol group vibration was detected in the silicified
      epidermal layer below and association with pectin and hemicelluloses indicated.
      Pectin and hemicelluloses (glucomannan) were found in high levels in the
      epidermal layer and in a clearly distinguished outer part of the hypodermal
      sterome fibers. The inner part of the two-layered cells revealed as almost pure
      cellulose, oriented parallel along the fiber.

PMID- 18057962
TI  - Dealing with indeterminacy in spatial descriptions.
AB  - How do people tackle indeterminate spatial descriptions, that is those
      descriptions for which several representations are possible? Take for instance
      the two following statements: B is to the left of A, C is to the left of A. This
      description is indeterminate because it is compatible with at least two
      possibilities: (1) C B A; (2) B C A. Studies on human reasoning have shown that
      people tend to reduce the complexity of such indeterminate descriptions by
      representing only one possibility. Which one do people favour? Is one possibility
      easier to work out than the other? Is one possibility more plausible than the
      other? Two competing hypotheses make different predictions about the
      representation people favour. If the building of the representation is driven by
      what we call manipulation difficulty, then (1) is more likely to be constructed
      than (2) because (2) results from reorganising the representation following the
      first statement where B is adjacent to A (i.e. B A) while (1) is just an
      extension of this initial representation. However, if the representation process
      is driven by pragmatic factors, then (2) is more likely to be built than (1)
      because the second statement could be interpreted as implicating "C is not to the
      left of B". Indeed, if C had been to the left of B it would have been more
      appropriate to utter, "C is to the left of B" rather than "C is to the left of
      A". Data from several experiments show that both manipulation difficulty and
      pragmatic factors play a role in determining participants' representations.

PMID- 18057963
TI  - Tumor development in three patients with Noonan syndrome.
AB  - The diagnosis of Noonan syndrome is essentially clinical, based upon the distinct
      phenotype and the involvement of the cardiovascular system. Tumor development is
      a rare manifestation of Noonan syndrome but can be explained by the molecular
      pathophysiology involved in the disorder. We present three Noonan patients who
      developed solid tumors. The first patient, a 4-year-old girl, developed granular
      cell tumors as did her mother in childhood. The second patient, a 1-year-old boy,
      had a low grade pilocytic astrocytoma, the clinical expression of which was
      persistent headache. MRI showed a pituitary mass in the posterior lobe. It was
      surgically removed. The third patient, a 7-year-old boy was found to have Sertoli
      tumors in his right cryptorchid testis. All three patients fulfilled the clinical
      criteria for Noonan syndrome. However, genetic testing was negative in patients 1
      and 3. The diagnosis of Noonan syndrome was made based on distinct phenotypic
      findings in three patients who had different types of tumors.

PMID- 18057964
TI  - Pitfalls in studies of children with monosymptomatic nocturnal enuresis.
AB  - In this issue Ferrara et al. present an important placebo-controlled, three-arm,
      double-blind, double-dummy, study on the treatment of nocturnal enuresis,
      demonstrating that homotoxicology is superior to placebo but less effective than
      desmopressin. Nocturnal enuresis is a disease with a heterogeneous aetiology and
      complex pathophysiology. The fact that different therapies may result in a wide
      range of responses is, therefore, not surprising. Differences in success rate
      can, therefore, be largely attributed to selection bias in the sub-populations.
      This consideration must be taken into account for every study design, to avoid
      premature interpretation of the results. Positive results in a paper are only not
      subject for discussion if both methodology and study population fulfil the
      highest standards, because negative results are not likely to be reported.
      Several points of weakness are present in the majority of studies, such as (a)
      inappropriate subtyping of the patients (terminology) or (b) epidemiological
      data, (c) insufficient documentation of patients' characteristics, (d) lack of
      plausible explanation as to why the placebo effect might be absent, (e) the
      heterogeneity of the severity of bedwetting. All these may lead to false positive
      and/or false negative results. In this commentary we try to tackle these
      different issues which might be relevant for the interpretation even of placebo
      controlled studies like that of Ferrara et al.

PMID- 18057965
TI  - Relationships between alpha diversity of plant species in bloom and climatic
      variables across an elevation gradient.
AB  - This study analyzes a 20-year record of flowering observations collected near
      Tucson, Arizona, USA. In contrast to traditional phenological records, this
      dataset is a record of all species observed in bloom collected in five segments
      of approximately 1 mile (1.61 km) in length across a 4,158-ft (1,200-m) elevation
      gradient. The data showed differing seasonal and interannual patterns,
      demonstrating the influence of climatic factors and elevation on flowering. Miles
      at higher elevations showed bloom peaks in summer, consistent with temperate and
      montane communities. Conversely, lower miles demonstrated two distinct flowering
      seasons, typical of the surrounding Sonoran Desert. Interannual fluctuations in
      total species observed in bloom were not consistent across the 5 miles (c. 8 km),
      suggesting that these communities respond to different flowering cues. Consistent
      with documented flowering triggers in semi-arid systems, the alpha diversity of
      species in bloom at lower elevations in this study was strongly influenced by
      precipitation. Upper elevation bloom numbers were heavily influenced by
      temperature, correspondent with bloom triggers in temperate and montane systems.
      In general, different life forms exhibited similar bloom triggers within the
      study miles, believed to be a function of shallow soils. Multivariate community
      analyses showed that anomalous climate conditions yielded unique seasonal bloom
      compositions. Over the course of the study, average summer temperature showed an
      upward trend; the number of species in bloom in summer (July-October) in the
      highest mile (1,940-2,210 m) demonstrated a concurrent increasing trend.
      Community analysis suggested a gradual shift in the composition of species in
      bloom in this mile over the study period.

PMID- 18057966
TI  - Scoliosis correction with pedicle screws in Duchenne muscular dystrophy.
AB  - This report describes the spinal fixation with pedicle-screw-alone constructs for
      the posterior correction of scoliosis in patients suffering from Duchenne
      muscular dystrophy (DMD). Twenty consecutive patients were prospectively followed
      up for an average of 5.2 years (min 2 years). All patients were instrumented from
      T3/T4 to the pelvis. Pelvic fixation was done with iliac screws similar to
      Galveston technique. The combination of L5 pedicle screws and iliac screws
      provided a stable caudal foundation. An average of 16 pedicle screws was used per
      patient. The mean total blood loss was 3.7 l, stay at the intensive care unit was
      77 h and hospital stay was 19 days. Rigid stabilisation allowed immediate
      mobilisation of the patient in the wheel chair. Cobb angle improved 77% from 44
      degrees to 10 degrees, pelvic tilt improved 65% from 14 degrees to 3 degrees.
      Lumbar lordosis improved significantly from 20 degrees to 49 degrees, thoracic
      kyphosis remained unchanged. No problems related to iliac fixation, no
      pseudarthrosis or implant failures were observed. The average percentage of
      predicted forced vital capacity (%FVC) of the patients was 55% (22-94%)
      preoperatively and decreased to 44% at the last follow-up. There were no
      pulmonary complications. One patient with a known cardiomyopathy died
      intraoperatively due to a sudden cardiac arrest. The rigid primary stability with
      pedicle screws allowed early mobilisation of the patients, which helped to avoid
      pulmonary complications.

PMID- 18057967
TI  - The impact of aerobic fitness on functioning in chronic back pain.
AB  - Despite lack of convincing evidence that reduced aerobic fitness is associated
      with chronic back pain (CBP), exercise programs are regarded as being effective
      for persons with non-specific CBP. It is unsure whether gain in aerobic fitness
      following intervention is associated with functioning improvement in persons with
      CBP. The objective of this prospective cohort study was to study the impact of
      aerobic fitness on functioning in persons with CBP, at baseline and following 3
      week intensive interdisciplinary intervention. This study included persons who
      had passed 8 weeks of sick-listing because of back pain (n = 94) and were
      referred to a 3-week intensive biopsychosocial rehabilitation program. Aerobic
      fitness was assessed with a sub-maximal bicycle test at baseline, at admission to
      and discharge from the rehabilitation program, and at 6 months follow-up.
      Contextual factors, body function, activity and participation were evaluated
      before and after intervention. In addition, working ability was recorded at 3
      years follow-up. At baseline aerobic fitness was reduced in most subjects, but
      improved significantly following intervention. Baseline measurements and
      intervention effects did not differ among the diagnostic sub-groups. Neither
      contextual factors nor functioning at baseline were associated with aerobic
      fitness. Increase in aerobic fitness was not associated with improvements in
      functioning and contextual factors and work-return following intervention either.
      From this study we conclude that improvement of aerobic fitness seems of limited
      value as goal of treatment outcome for patients with CBP.

PMID- 18057968
TI  - Spinal extra-dural metastasis from Merkel cell carcinoma: a rare cause of
      paraplegia.
AB  - We report a rare case of Merkel cell carcinoma with extra-dural spinal metastasis
      causing paraplegia. There are only four reported cases in literature. A 57-year
      old lady presented with a breast lump, multiple truncal skin swellings, low back
      pain and rapidly progressive paraplegia. MRI showed multiple epidural soft tissue
      masses causing neural compression. A biopsy from the truncal skin lesion was
      diagnosed as Merkel cell carcinoma (MCC). Posterior decompression and tumor
      debulking at all three sites of neural compression was performed. Histopathology
      of the epidural tumor was consistent with MCC and the diagnosis was confirmed by
      immuno-histochemistry staining for cytokeratin-20. She was started on
      chemotherapy and radiotherapy. One month after diagnosis she died due to
      extensive metastasis. The short term palliative response seen in our patient
      demonstrates the poor prognosis for patients with spinal metastasis.

PMID- 18057969
TI  - Systematic development of computational models for the catalytic site in
      galactose oxidase: impact of outer-sphere residues on the geometric and
      electronic structures.
AB  - A systematic in silico approach has been employed to generate sound,
      experimentally validated active-site models for galactose oxidase (GO) using a
      hybrid density functional, B(38HF)P86. GO displays three distinct oxidation
      states: oxidized [Cu(II)-Y*]; semireduced [Cu(II)-Y]; and reduced [Cu(I)-Y]. Only
      the [Cu(II)-Y*] and the [Cu(I)-Y] states are assumed to be involved in the
      catalytic cycle, but their structures have not yet been determined. We have
      developed several models (1-7) for the [Cu(II)-Y*] state that were evaluated by
      comparison of our computational results with experimental data. An extended model
      system (6) that includes solvent molecules and second coordination sphere
      residues (R330, Y405, and W290) is essential to obtain an experimentally correct
      electronic structure of the active site. The optimized structure of 6 resulted in
      a five-coordinate Cu site with a protein radical centered on the Tyr-Cys
      cofactor. We further validated our converged model with the largest model (7)
      that included additional outer-sphere residues (Q406, H334, Y329, G513, and T580)
      and water molecules. Adding these residues did not affect significantly the
      active site's electronic and geometric structures. Using both 6 and 7, we
      explored the redox dependence of the active-site structure. We obtained four- and
      three-coordinate Cu sites for [Cu(II)-Y] and [Cu(I)-Y] states, respectively, that
      corroborate well with the experimental data. The relative energies of these
      states were validated by a comparison with experimental redox potentials.
      Collectively, our computational GO models well reproduce the physicochemical
      characteristics of the individual states, including their redox behaviors.

PMID- 18057970
TI  - A new method for chlorhexidine (CHX) determination: CHX release after application
      of differently concentrated CHX-containing preparations on artificial fissures.
AB  - Aims of the study were (1) to establish a method for quantification of
      chlorhexidine (CHX) in small volumes and (2) to determine CHX release from
      differently concentrated CHX-containing preparations, varnishes, and a CHX gel
      applied on artificial fissures. CHX determination was conducted in a microplate
      reader using polystyrene wells. The reduced intensity of fluorescence of the
      microplates was used for CHX quantification. For verification of the technique,
      intra- and inter-assay coefficients of variation were calculated for graded
      series of CHX concentrations, and the lower limit of quantification (LLOQ) was
      determined. Additionally, artificial fissures were prepared in 50 bovine enamel
      samples, divided into five groups (A-E, n=10) and stored in distilled water (7
      days); A: CHX-varnish EC40; B: CHX-varnish Cervitec; C: CHX-gel Chlorhexamed; D:
      negative control, no CHX application; and E: CXH-diacetate standard (E1, n=5) or
      CHX-digluconate (E2, n=5) in the solution. The specimens were brushed daily, and
      CHX in the solution was measured. The method showed intra- and inter-assay
      coefficients of variation of <10 and <20%, respectively; LLOQ was 0.91-1.22
      nmol/well. The cumulative CHX release (mean+/-SD) during the 7 days was: EC40
      (217.2+/-41.8 nmol), CHX-gel (31.3+/-8.5 nmol), Cervitec (18.6+/-1.7 nmol).
      Groups A-C revealed a significantly higher CHX release than group D and a
      continuous CHX-release with the highest increase from day 0 to 7 for EC40 and the
      lowest for Chlorhexamed. The new method is a reliable tool to quantify CHX in
      small volumes. Both tested varnishes demonstrate prolonged and higher CHX release
      from artificial fissures than the CHX-gel tested.

PMID- 18057971
TI  - Myotonic dystrophy type 2 in Japan: ancestral origin distinct from Caucasian
      families.
AB  - Myotonic dystrophy type 2 (DM2) is caused by expansion of a tetranucleotide CCTG
      repeat in intron 1 of the ZNF9 gene on chromosome 3q21. All studied DM2 mutations
      have been reported in Caucasians and share an identical haplotype, suggesting a
      common founder. We identified a Japanese patient with DM2 and showed that the
      affected haplotype is distinct from the previously identified DM2 haplotype
      shared among Caucasians. These data strongly suggest that DM2 expansion mutations
      originate from separate founders in Europe and Japan and are more widely
      distributed than previously recognized.

PMID- 18057972
TI  - Paradoxical growth effects of the echinocandins caspofungin and micafungin, but
      not of anidulafungin, on clinical isolates of Candida albicans and C.
      dubliniensis.
AB  - OBJECTIVES: To analyze the effects of a high concentration of three antifungal
      substances, the echinocandins anidulafungin, caspofungin, and micafungin, on the
      growth of Candida spp. METHODS: The growth of 127 C. dubliniensis isolates and
      103 C. albicans isolates cultured in medium containing anidulafungin,
      caspofungin, or micafungin was analyzed using a broth microdilution test
      according to the guidelines of the CLSI M27-A2 [NCCLS (1997), Wayne, PA]. The
      final concentrations of all three echinocandins ranged from 0.125 to 64 microg/L.
      RESULTS: The different effects of these three antifungal substances on C.
      albicans cells in comparison to C. dubliniensis cells were quite distinct. When
      both Candida species were grown in the presence of anidulafungin only a trailing
      effect was observed. Micafungin induced an Eagle effect in C. dubliniensis only
      (63%), while caspofungin induced this effect in the majority of C. dubliniensis
      isolates (90%) and in only a few C. albicans isolates (14%). CONCLUSIONS: Based
      on our observations, anidulafungin has effects that are different from the ones
      produced by micafungin and caspofungin. Whether this different response to high
      concentrations of echinocandins is based on genetic or phenotypic differences
      between C. albicans and C. dubliniensis has to be determined in future
      experiments.

PMID- 18057973
TI  - Impact of fermentation pH and temperature on freeze-drying survival and membrane
      lipid composition of Lactobacillus coryniformis Si3.
AB  - During the industrial stabilization process, lactic acid bacteria are subjected
      to several stressful conditions. Tolerance to dehydration differs among lactic
      acid bacteria and the determining factors remain largely unknown. Lactobacillus
      coryniformis Si3 prevents spoilage by mold due to production of acids and
      specific antifungal compounds. This strain could be added as a biopreservative in
      feed systems, e.g. silage. We studied the survival of Lb. coryniformis Si3 after
      freeze-drying in a 10% skim milk and 5% sucrose formulation following different
      fermentation pH values and temperatures. Initially, a response surface
      methodology was employed to optimize final cell density and growth rate. At
      optimal pH and temperature (pH 5.5 and 34 degrees C), the freeze-drying survival
      of Lb. coryniformis Si3 was 67% (+/-6%). The influence of temperature or pH
      stress in late logarithmic phase was dependent upon the nature of the stress
      applied. Heat stress (42 degrees C) did not influence freeze-drying survival,
      whereas mild cold- (26 degrees C), base- (pH 6.5), and acid- (pH 4.5) stress
      significantly reduced survival. Freeze-drying survival rates varied fourfold,
      with the lowest survival following mild cold stress (26 degrees C) prior to
      freeze-drying and the highest survival after optimal growth or after mild heat
      (42 degrees C) stress. Levels of different membrane fatty acids were analyzed to
      determine the adaptive response in this strain. Fatty acids changed with altered
      fermentation conditions and the degree of membrane lipid saturation decreased
      when the cells were subjected to stress. This study shows the importance of
      selecting appropriate fermentation conditions to maximize freeze-drying viability
      of Lb. coryniformis as well as the effects of various unfavorable conditions
      during growth on freeze-drying survival.

PMID- 18057974
TI  - Functional MRI at 3T using intermolecular double-quantum coherence (iDQC) with
      spin-echo (SE) acquisitions.
AB  - OBJECT: To reinvestigate the dependence of the signal and contrast on sequence
      parameters and tissue relaxation times for intermolecular double-quantum
      coherence (iDQC) signals, and to explore the possibility to use a spin-echo (SE)
      iDQC sequence for detecting activation signals at 3T. MATERIALS AND METHODS:
      Brain activations were detected in five human volunteers in a visual simulation
      study using a SE-iDQC sequence, in addition to a GE-iDQC and a conventional
      single-quantum coherence (SQC) blood-oxygenation-level-dependent (BOLD) sequence.
      A brain phantom was also used for some quantitative measurements. RESULTS: By
      choosing an optimal echo time TE (approximately T2) and iDQC evolution time
      tau(approximately 20 ms), robust brain activations were detected using the SE
      iDQC sequence, in addition to the GE-iDQC and a conventional single-quantum
      coherence (SQC) BOLD sequence. A higher percentage signal change due to
      activation was observed for both the iDQC-based measurements in comparison to the
      conventional SQC acquisition. CONCLUSION: Even though a phenomenological analysis
      consistent with the experimental results was provided, a detailed model is still
      needed for the contrast mechanism at microscopic level to guide potential
      applications of brain functional imaging based on the SE-iDQC.

PMID- 18057975
TI  - Optimized quadrature surface coil designs.
AB  - BACKGROUND: Quadrature surface MRI/MRS detectors comprised of circular loop and
      figure-8 or butterfly-shaped coils offer improved signal-to-noise-ratios (SNR)
      compared to single surface coils, and reduced power and specific absorption rates
      (SAR) when used for MRI excitation. While the radius of the optimum loop coil for
      performing MRI at depth d in a sample is known, the optimum geometry for figure-8
      and butterfly coils is not. MATERIALS AND METHODS: The geometries of figure-8 and
      square butterfly detector coils that deliver the optimum SNR are determined
      numerically by the electromagnetic method of moments. Figure-8 and loop detectors
      are then combined to create SNR-optimized quadrature detectors whose theoretical
      and experimental SNR performance are compared with a novel quadrature detector
      comprised of a strip and a loop, and with two overlapped loops optimized for the
      same depth at 3 T. The quadrature detection efficiency and local SAR during
      transmission for the three quadrature configurations are analyzed and compared.
      RESULTS: The SNR-optimized figure-8 detector has loop radius r8 approximately
      0.6d, so r8/r0 approximately 1.3 in an optimized quadrature detector at 3 T. The
      optimized butterfly coil has side length approximately d and crossover angle of >
      or = 150 degrees at the center. CONCLUSIONS: These new design rules for figure-8
      and butterfly coils optimize their performance as linear and quadrature
      detectors.

PMID- 18057976
TI  - Low intense physical exercise in normobaric hypoxia leads to more weight loss in
      obese people than low intense physical exercise in normobaric sham hypoxia.
AB  - Training in mild to moderate hypoxia (14-17% O(2) in breathing air) and extended
      resting in moderate hypoxia (9-13% O(2)) have been shown to have effects in
      animals and humans on lipid and glucose metabolism, appetite loss, and, in part,
      on body weight. The causality for these effects is not yet known in detail, and
      the available data in humans from high-altitude and low-pressure chamber studies
      are scarce. New technical developments by German companies in the production of
      artificial climates with normobaric hypoxic conditions in larger rooms at
      reasonable energy costs allow now to perform hypoxia weight loss studies in obese
      humans with stable experimental conditions and protocols with a sham hypoxia
      control. Thirty-two obese people were recruited for a mild intense training study
      in normobaric hypoxia (15 vol.% O(2)) and normoxia/sham hypoxia (20.1 vol.%
      O(2)). Twenty of these [mean age 47.6 years, mean body mass index (BMI) 33.1, 16
      m, 4 f) were willing to follow up on an 8-week, three times per week, 90-min low
      intense physical exercise in their individual fat burning mode, which has been
      determined by an exercise testing with spiro-ergometry upfront. The subjects were
      evenly randomized into a hypoxia and sham hypoxia group. The difference of the
      two groups in weight loss and changes in HBa1C values were analyzed before and
      after the training period. No nutritional diet was applied. Subjects in the
      hypoxia group in mean lost significantly more weight than in the sham hypoxia
      group (Delta1.14 kg vs Delta0.03 kg; p = 0.026). This resulted in a tendency to
      reduce the BMI more in the hypoxia group (p = 0.326). In the mean, there was no
      HbA1C exceeding normal values (mean 5.67 and 5.47%), and the HbA1C stayed
      basically unchanged after the 8-week training. Mild physical exercise three times
      per week for 90 min in normobaric hypoxia for 8 weeks led to significantly
      greater weight loss in obese persons than the exercise in sham hypoxia in this,
      to our knowledge, first sham hypoxia controlled study.

PMID- 18057977
TI  - Prediction of the susceptibility to AMS in simulated altitude.
AB  - Acute mountain sickness (AMS) develops when rapidly ascending to high altitudes.
      However, some mountaineers will suffer from AMS even at 2,000 m and others not
      until 5,000 m. The awareness of the individual susceptibility for AMS would be
      helpful for preventive strategies. Thus, the main purpose of this paper is the
      comparison of existing studies dealing with the prediction of AMS susceptibility
      and to draw conclusions on presently most valuable tests. DATA SOURCE: A PubMed
      search has been performed, and preliminary observations from our laboratory have
      been included. The cautious conclusion derived from the reviewed 16 studies is
      that values of arterial oxygen saturation (SaO(2)), determined 20-30 min after
      exposure to simulated hypoxia equivalent to 2,300-4,200 m, seem to be the most
      useful predictors of AMS susceptibility (>80% correct prediction). Because the
      sympathetic activation during acute exposure to hypoxia may well contribute to
      the AMS development, parameters like heart rate variability or blood lactate
      could even enhance this predictability. The ventilatory response to hypoxia is
      easily trainable by pre-exposures to hypoxia but considers only part of the
      complex acclimatization process.

PMID- 18057978
TI  - Solitary angiokeratoma of the tongue treated with diode laser.
AB  - Angiokeratoma is a muco-cutaneous disorder that is usually associated with a
      number of metabolic disorders. Involvement of the tongue with solitary
      angiokeratoma, without a systemic or metabolic disease, is very rare. To the best
      of our knowledge, we report the second case of solitary angiokeratoma of the
      tongue arising in a 16-year-old woman who was treated with diode laser (810 nm)
      in our department.

PMID- 18057979
TI  - Apolipoprotein E promoter polymorphisms (-491A/T and -427T/C) and Alzheimer's
      disease: no evidence of association in the Irish population.
AB  - BACKGROUND: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder
      with as yet poorly understood aetiology. Both environmental and genetic factors
      have been implicated as predisposing factors. The APOE e4 allele is an
      established genetic susceptibility factor for AD for several populations
      including the Irish. Polymorphisms (-491A/T and -427T/C) at the promoter region
      of the APOE gene are postulated to affect the expression of the gene through
      differential binding of transcription factors. AIMS: Two APOE promoter
      polymorphisms (-491A/T and -427T/C) are examined for possible association with
      AD. METHODS: Using a case-control study design, a sample of 112 Irish late onset
      Alzheimer's (LOAD) patients and 107 ethnically matched controls were investigated
      for association with the above polymorphisms. CONCLUSIONS: No evidence of
      association between any of the examined markers and AD was observed. Haplotype
      analysis using markers -491A/T and -427T/C in conjunction with the APOE (Hha I)
      polymorphism revealed significant associations of three haplotypes with AD.
      However, this association was mainly due to the highly significant association of
      the APOE e4 allele with AD and not of the promoter variants.

PMID- 18057982
TI  - Setting up a surgical skills center.
AB  - With the increasing use of simulation in medicine, many departments of surgery
      are considering the development of a surgical skills center. This article focuses
      on practical issues that must be considered when setting up a surgical skills
      center. The importance of developing a mission statement and including relevant
      stakeholders is discussed. The types of curricula that can be developed as well
      as the appropriate equipment purchased to support different curricula are
      considerations. Space requirements, funding sources, and staffing are also
      covered. Setting up a surgical skills center requires institutional buy-in and
      planning from the outset. Various models of skills centers, depending on local
      politics, are discussed.

PMID- 18057983
TI  - Systematic management of postoperative enterocutaneous fistulas: factors related
      to outcomes.
AB  - BACKGROUND: Most enterocutaneous fistulas are postoperative in origin. Sepsis,
      malnutrition, and hydroelectrolytic deficit are still the most important
      complications to which patients with postoperative enterocutaneous fistulas (PEF)
      are exposed. Knowledge of prognostic factors related to specific outcomes is
      essential for therapeutic decision-making processes. METHODS: We reviewed files
      of all consecutive patients with PEF treated in our hospital during a 10-year
      period. Our aim was to identify factors related to spontaneous closure, need for
      operative treatment, and mortality. Univariate and multivariate analyses were
      performed. RESULTS: A total of 174 patients were treated. The most frequent site
      of origin was the small bowel (90 patients: 48 jejunal, and 42 ileal), followed
      in frequency by the colon (50 patients). Postoperative enterocutaneous fistula
      closure was achieved in 151 patients (86%), being spontaneous in 65 (37%) and
      surgical in 86 (49%). Factors that significantly precluded spontaneous closure
      were jejunal site, multiple fistulas, sepsis, high output, and hydroelectrolytic
      deficit at diagnosis or referral. Origin of PEF at our hospital was the only
      factor significantly associated with spontaneous closure. The most frequent
      operative indication was PEF persistence without sepsis. Factors significantly
      associated with the need for operative treatment were high output, jejunal site,
      and multiple fistulas. Closure was achieved in 84% of patients who underwent
      operation. A total of 23 patients died (13%). Factors associated with mortality
      were serum albumin <3.0 g/dl (at diagnosis or referral), high output,
      hydroelectrolytic deficit, multiple fistulas, jejunal site, sepsis, and a complex
      fistulous tract. CONCLUSIONS: In spite of advances in management of PEF, the
      associated morbidity and mortality remain high. Among several variables
      influencing outcome, our multivariate analysis disclosed high output, jejunal
      site, multiple fistulas, and sepsis as independent adverse factors related to non
      spontaneous closure, need for operative treatment, and/or death.

PMID- 18057984
TI  - CRC surgery trends in Kenya, 1993-2005.
AB  - BACKGROUND: CRC (CRC) rates are low but increasing in Africa. Data on detection,
      treatment, and outcome are scarce. OBJECTIVE: The aim of this study was to
      evaluate the presentation, treatment, and outcome pattern of CRC and to compare
      the care processes for two time periods. SETTING: The setting was Kenyatta
      National Hospital (KNH), a teaching and referral center. PATIENTS AND METHODS: A
      total of 259 patients seen over two time periods (1993-1998 and 1999-2005) were
      analyzed for admission date, sex, subsite involvement, diagnostic process,
      treatment, follow-up, and outcome. The distribution of variables between the time
      periods were analyzed using Student's t-test and chi2 as appropriate. Survival
      trends were generated using Kaplan Meier method; p<0.05 was statistically
      significant. RESULTS: The average number of CRC diagnoses showed a 2.7-fold
      increase during the study periods. The mean age at presentation was 49.7 years.
      The mean duration of symptoms was 29.6 weeks; and the commonest subsite was the
      rectum (55.3%). The overall resection rate was 67.7%. For rectal tumors the
      abdominoperineal rate was 51.4%. Mortality was higher for poorly differentiated
      cancer, advanced disease, age>50 years, and emergency surgery. There was no
      change in the age, duration of symptoms, proportion of patients<40 years, or the
      colon/rectal ratios of the cancer site. The second time period saw more adjuncts
      for diagnosis, less in-hospital mortality, and better staging data. CONCLUSION:
      CRC peaks during the fifth decade of life in Kenyans. The disease is
      characterized by late presentation, rectal preponderance, and inadequate
      pathology data. Improved patient follow-up will unravel the true pattern of
      disease outcome.

PMID- 18057985
TI  - MR reproducibility in the assessment of uterine fibroids for patients scheduled
      for uterine artery embolization.
AB  - Magnetic resonance imaging (MRI) is increasingly applied in the evaluation of
      uterine fibroids. However, little is known about the reproducibility of MRI in
      the assessment of uterine fibroids. This study evaluates the inter- and
      intraobserver variation in the assessment of the uterine fibroids and concomitant
      adenomyosis in women scheduled for uterine artery embolization (UAE). Forty
      patients (mean age: 44.5 years) with symptomatic uterine fibroids who were
      scheduled for UAE underwent T(1)- and T(2)-weighted MRI. To study inter- and
      intraobserver agreement 40 MR images were evaluated independently by two
      observers and reevaluated by both observers 4 months later. Inter- and
      intraobserver agreement was calculated using Cohen's kappa statistic and
      intraclass correlation coefficient for categorical and continuous variables,
      respectively. Inter-observer agreement for uterine volumes (kappa = 0.99, p <
      0.0001), dominant fibroid volumes (kappa = 0.98, p <or= 0.0001), and number of
      fibroids (kappa = 0.88; CI, 0.77-0.93; p < 0.0001) was excellent. For the T(1)-
      and T(2)-weighted signal intensity of the dominant fibroid there was good
      agreement between the observers (87%; 95% CI, 71.9%-95.6%) and the intraobserver
      agreement was good for observer A (95%; 95% CI, 83.1%-99.4%) and moderate for
      observer B (kappa = 0.47). The interobserver agreement with respect to the
      presence of adenomyosis was good (kappa = 0.73, p < 0.0001), while both
      intraobserver agreements were fair to moderate (observer A, kappa = 0.55, p =
      0.0003; and observer B, kappa = 0.66, p < 0.0001). In conclusion, MRI criteria
      used for the selection of suitable UAE patients show good inter- and
      intraobserver reproducibility.

PMID- 18057987
TI  - Floral odors of Silene otites: their variability and attractiveness to
      mosquitoes.
AB  - Inflorescence scent samples from nine populations of dioecious Silene otites, a
      plant pollinated by moths and mosquitoes, were collected by dynamic headspace
      extraction. Sixty-three scent samples were analyzed by gas chromatography-mass
      spectrometry. Out of 38 found, 35 compounds were identified, most of which were
      monoterpenoids, fatty acid derivatives, and benzenoids. Phenyl acetaldehyde was
      the most dominant compound in the majority of samples. The variability in scent
      composition was high, and population and sex differences were found.
      Nevertheless, wind tunnel experiments proved similar attraction of Culex pipiens
      pipiens biotype molestus mosquitoes to the inflorescence odor of S. otites of
      different populations, indicating that different blends are similarly attractive
      to mosquitoes. The electrophysiological responses of mosquitoes to the 12 most
      common and abundant odor compounds of S. otites differed. Linalool oxide
      (furanoid) and linalool evoked the strongest responses in male and female
      mosquitoes, and (Z)-3-hexenyl acetate was strongly active in females. Medium
      responses were evoked in males by (Z)-3-hexenyl acetate, in females by
      benzaldehyde and methyl salicylate, and in both sexes by lilac aldehyde, lilac
      alcohol, and linalool oxide (pyranoid).

PMID- 18057986
TI  - Rapid hair cell loss: a mouse model for cochlear lesions.
AB  - In comparison to other mammals, mice have proved extremely resistant to
      aminoglycoside-induced hair cell ablation in vivo. In this paper we examine the
      pattern and extent of cochlear lesions rapidly induced with a combination of a
      single dose of aminoglycoside (kanamycin) followed by a loop diuretic
      (bumetanide). With this protocol, the vestibular system was unaffected, but in
      the cochlea, there was extensive loss of outer hair cells (OHC) that commenced in
      the basal coil and progressed apically so that, by 48 h, OHC loss was almost
      complete. TUNEL-positive nuclei and activated caspase-3 labeling demonstrated
      that most OHC died via a classical apoptotic pathway. However, scattered debris
      within the OHC region suggested that many apoptotic cells ruptured prior to
      completion of apoptosis. Following lesion repair, supporting cells retained
      characteristics of differentiated cells but positional shift occurred. In
      comparison to OHC loss, inner hair cell (IHC) death was delayed and only observed
      in 50% of all cochleae examined even after extensive reorganization of the
      tissue. The coadmininstration of diuretic with FM1-43, used as a tracer for
      aminoglycoside uptake, indicated entry into IHC as readily as OHC, suggesting
      that the differential response to aminoglycoside was not due to differential
      uptake. Where IHC death was ongoing, there were indications of different modes of
      cell death: cells with morphological features of autophagy, necrosis, and
      apoptosis were apparent. In addition to damage to the organ of Corti, there was a
      significant and progressive decrease in strial thickness beginning as early as 7
      days posttreatment. This was due predominantly to degeneration of marginal cells.
      The strial pathology resembled that reported after noise damage and with aging.
      This in vivo protocol provides a robust model in which to obtain extensive OHC
      loss in the mature cochleae of mice and is a means with which to examine
      different aspects of cochlear pathology in transgenic or mutant strains.

PMID- 18057988
TI  - Swedish experience with peritonectomy and HIPEC. HIPEC in peritoneal
      carcinomatosis.
AB  - BACKGROUND: Peritonectomy with heated intraperitoneal chemotherapy (HIPEC) has
      shown a survival benefit in selected patients with peritoneal carcinomatosis.
      This prospective non-randomized study was designed to identify factors associated
      with postoperative morbidity and survival after peritonectomy HIPEC in patients
      with this condition. METHOD: Data were prospectively collected from all patients
      with peritoneal carcinomatosis treated by means of peritonectomy and HIPEC at
      Uppsala University Hospital between October 2003 and September 2006. Depending on
      the primary tumor, mitomycin C or a platinum compound was used as a
      chemotherapeutic agent for perfusion. RESULTS: A total of 103 patients were
      treated. Primary tumors were pseudomyxoma peritonei (47 patients), colorectal
      cancer (38 patients), gastric cancer (6 patients), ovarian cancer (6 patients)
      and mesothelioma (5 patients). Postoperative morbidity was 56.3% and was
      significantly lower in patients treated with mitomycin C for pseudomyxoma
      peritonei (42%) than in those with another diagnosis treated with platinum
      compound (71%, P < 0.05). Postoperative mortality was less than 1%. At 2 years,
      overall survival was estimated to be 72.3%, and disease-free survival was 33.5%.
      Factors influencing overall and disease-free survival were tumor type and optimal
      cytoreduction. CONCLUSION: Postoperative morbidity is dependent mainly on a tumor
      type; however, the chemotherapeutic agent used might also influence morbidity.
      Survival is determined by optimal cytoreduction and tumor type. Irrespective of
      age, patients with good performance status benefit from this treatment.

PMID- 18057990
TI  - Reexcisions in breast-conserving surgery for breast cancer: can they be avoided?

PMID- 18057989
TI  - Lateral lymph node metastasis is a major cause of locoregional recurrence in
      rectal cancer treated with preoperative chemoradiotherapy and curative resection.
AB  - BACKGROUND: In rectal cancer patients treated with preoperative chemoradiotherapy
      (CRT) and curative resection, we evaluated the effect of clinical parameters on
      lateral pelvic recurrence and made an attempt to identify a risk factor for
      lateral pelvic recurrence. METHODS: The study involved 366 patients who underwent
      preoperative CRT and curative resection between October 2001 and December 2005.
      Clinical parameters such as gender, age, tumor size, histologic type, cT and cN
      classification, ypT and ypN classification, circumferential resection margin,
      tumor regression grade, chemotherapeutic regimen, and lateral lymph node size
      were analyzed to identify risk factors associated with lateral pelvic recurrence.
      RESULTS: Of the 366 patients, 29 patients (7.9%) had locoregional recurrence: 6
      (20.7%) with central pelvic recurrence and 24 (82.7%) had lateral pelvic
      recurrence, of which 1 had simultaneous central and lateral pelvic recurrence.
      Multivariate analysis showed that ypN classification and lateral lymph node size
      were significantly associated with lateral pelvic recurrence (P < .001). Of 250
      ypN0 patients, lateral pelvic recurrence developed in 1.4%, 2.9%, and 50% of
      patients with lateral lymph node sizes of < 5, 5-9.9, and > or = 10 mm,
      respectively (P < .001). Of 116 ypN+ patients, lateral pelvic recurrence
      developed in 4.3%, 35.7%, and 87.5% of patients with lateral lymph node sizes of
      < 5, 5-9.9, and > or = 10 mm, respectively (P < .001). CONCLUSIONS: In our study,
      lateral pelvic recurrence was a major cause of locoregional recurrence, and ypN+
      and lateral lymph node size were risk factors for lateral pelvic recurrence.

PMID- 18057991
TI  - Prognosis of perihilar cholangiocarcinoma: hilar bile duct cancer versus
      intrahepatic cholangiocarcinoma involving the hepatic hilus.
AB  - BACKGROUND: Clinically hepatobiliary resection is indicated for both hilar bile
      duct cancer (BDC) and intrahepatic cholangiocarcinoma involving the hepatic hilus
      (CCC). The aim of this study was to compare the long-term outcome of BDC and CCC.
      METHODS: Between 1990 and 2004, we surgically treated 158 consecutive patients
      with perihilar cholangiocarcinoma. The clinicopathological data on all of the
      patients were analyzed retrospectively. RESULTS: The overall 3-year survival
      rate, 5-year survival rate, and median survival time for BDC patients were 48.4%,
      38.4 %, and 33.7 months, respectively, and 35.8%, 24.5 %, and 22.7 months,
      respectively, in CCC patients (P = .033). On multivariate analysis, three
      independent factors were related to longer survival in BDC patients: achieved in
      curative resection with cancer free margin (R0) (P = .024, odds ratio 1.862),
      well differentiated or papillary adenocarcinoma (P = .011, odds ratio 2.135), and
      absence of lymph node metastasis (P < .001, odds ratio 3.314). Five factors were
      related to longer survival in CCC patients: absence of intrahepatic daughter
      nodules (P < .001, odds ratio 2.318), CEA level </=2.9 ng/mL (P = .005, odds
      ratio 2.606), no red blood cell transfusion requirement (P = .016, odds ratio
      2.614), absence or slight degree of lymphatic system invasion (P < .001, odds
      ratio 4.577), and negative margin of the proximal bile duct (P = .003, odds ratio
      7.398). CONCLUSIONS: BDC and CCC appear to have different prognoses after
      hepatobiliary resection. Therefore, differentiating between these two categories
      must impact the prediction of postoperative survival in patients with perihilar
      cholangiocarcinoma.

PMID- 18057992
TI  - Breast conservation therapy: multiple reexcisions or subcutaneous and nipple
      sparing mastectomy?

PMID- 18057993
TI  - Concurrent chemoradiotherapy or endoscopic stenting for advanced squamous cell
      carcinoma of esophagus: a case-control study.
AB  - BACKGROUND: We evaluated the role of chemoradiotherapy (CRT) for patients with
      inoperable squamous esophageal cancer. METHODS: Patients with locally advanced or
      metastatic squamous esophageal carcinoma who received CRT were recruited. The CRT
      consists of continuous infusion of 5-fluorouracil at 200 mg/m(2)/day, and
      cisplatin at 60 mg/m(2) on days 1 and 22, with concurrent radiotherapy for a
      total of 50 to 60 Gy in 25 to 30 fractions over 6 weeks. Efficacy was assessed by
      endoscopy and computed tomographic scan before and 8 weeks after completion of
      the treatment program. Median survival and the need for palliative esophageal
      stenting were compared with another group of patients who received endoscopic
      stenting. RESULTS: From 1996 to 2003, a total of 36 consecutive patients (33
      male, mean +/- SD age 63.2 +/- 9.5 years) with T4 disease (81%) with or without
      cervical nodal metastasis (50%) received CRT, while 36 patients treated with
      endoscopic stenting alone were recruited as controls. Both groups were comparable
      in demographics, pretreatment dysphagia score, comorbidities, and tumor
      characteristics. CRT was completed in 32 patients (89%). There was no treatment
      related mortality. Tumor volume was greatly reduced after CRT in 19 patients.
      Four patients (11%) received salvage esophagectomy 9 to 42 months after CRT.
      Compared with the stenting group, CRT statistically significantly improved 5-year
      survival (15% vs. 0%, P = .01), median survival (10.8 months vs. 4.0 months, P <
      .005), and need for stenting (22% vs. 100%, P = .005). CONCLUSIONS: Palliative
      CRT can effectively improve the symptoms of dysphagia in patients with inoperable
      squamous esophageal carcinoma. It results in better survival compared with
      endoscopic stenting in these patients.

PMID- 18057994
TI  - Synthetic extracellular matrix enhances tumor growth and metastasis in an
      orthotopic mouse model of pancreatic adenocarcinoma.
AB  - Individuals with pancreatic cancer have one of the poorest survival rates among
      the major cancers, suggesting the need to develop new therapeutic approaches. An
      effective animal model that mimics the progression and metastases of human
      pancreatic adenocarcinoma does not exist. The goal of this investigation was to
      develop a model that would compare the growth and metastasis of orthotopically
      injected pancreatic cancer cells to cells encapsulated within a synthetic
      extracellular matrix (sECM). The hypotheses tested were that the cells within the
      sECM would grow more quickly and more frequently develop metastasis to distant
      organs. MiaPaCa-2 cells expressing red fluorescent protein, either in serum-free
      media or within a hyaluronan-based hydrogel, were injected into the pancreas of
      nude mice. Tumors were monitored for 8 weeks via intravital red fluorescent
      protein imaging. Cells encapsulated within the sECM grew more quickly and
      produced larger tumors compared with the cells alone. In addition, the cells
      within the sECM developed metastasis more frequently. Therefore, the
      encapsulation of human pancreatic cancer cells within an injectable sECM improved
      the rate of tumor growth and metastasis in an orthotopic mouse model. The
      advantages of this new approach can be utilized to investigate the mechanisms of
      tumor progression and test novel therapeutic agents in vivo.

PMID- 18057995
TI  - Natural orifice translumenal endoscopic surgery: a critical review.
AB  - Natural orifice translumenal endoscopic surgery (NOTES) involves the intentional
      puncture of one of the viscera (e.g., stomach, rectum, vagina, urinary bladder)
      with an endoscope to access the abdominal cavity and perform an intraabdominal
      operation. Early laboratory work focused on feasibility studies, including such
      accomplishments as pure transgastric splenectomy and gastrojejunostomy.
      Contemporary laboratory work is investigating the infectious and immunologic
      implications of NOTES and honing the tools and techniques required for complex
      abdominal operations. Today NOTES has entered the clinical arena in a few cases:
      the first clinical series of transgastric peritoneoscopy has recently been
      published; multiple groups are accumulating patients in studies of NOTES
      cholecystectomy, either via the transgastric or transvaginal route; and a series
      of transgastric appendectomies has been well publicized, yet it remains
      unpublished. Although clinical NOTES is gaining momentum, the field should remain
      in check while rigorous laboratory work is performed and cogent clinical trials
      are undertaken. The zeal for NOTES should not take precedence over the welfare of
      the patient.

PMID- 18057997
TI  - Calmodulin binding is dispensable for Rem-mediated Ca2+ channel inhibition.
AB  - GTPases of the Ras-related RGK family are negative regulators of high voltage
      activated (HVA) Ca2+ channel activity. In this study, we examined the role of
      calmodulin (CaM) association in Rem-mediated Ca2+ channel inhibition. We found
      that the Rem/CaM interaction is Ca2+-dependent, and that truncation of the Rem C
      terminus before position 277 prevents CaM binding. Serial mutagenesis of the Rem
      C-terminus between residues 265 and 276 to alanine generated two mutants
      (Rem(L271A) and Rem(L274A)) that displayed reduced CaM binding, and a subset of
      these mutants displayed significantly lower cell periphery localization than
      Rem(WT). However, reductions in CaM association or membrane trafficking did not
      affect function, as all Rem mutants could completely inhibit Ca2+ channels. The
      Rem(1-275) truncation mutant partially inhibited Ca2+ channel activity despite
      its inability to bind CaM. Taken together, these studies indicate that CaM
      association is not essential for either Rem-mediated Ca2+ channel inhibition or
      plasma membrane localization.

PMID- 18057996
TI  - Chymase induces profibrotic response via transforming growth factor-beta 1/Smad
      activation in rat cardiac fibroblasts.
AB  - Mast cell-derived chymase is implicated in myocardial fibrosis (MF), but the
      underlying mechanism of intracellular signaling remains unclear. Transforming
      growth factor-beta 1 (TGF-beta1) is identified as the most important profibrotic
      cytokine, and Smad proteins are essential, but not exclusive downstream
      components of TGF-beta 1 signaling. Moreover, novel evidence indicates that there
      is a cross talk between Smad and mitogen-activated protein kinase (MAPK)
      signaling cascade. We investigated whether chymase activated TGF-beta 1/Smad
      pathway and its potential role in MF by evaluating cardiac fibroblasts (CFs)
      proliferation and collagen synthesis in neonatal rats. MTT assay and 3H-Proline
      incorporation revealed that chymase induced CFs proliferation and collagen
      synthesis in a dose-dependent manner. RT-PCR and Western blot assay demonstrated
      that chymase not only increased TGF-beta1 expression but also upregulated
      phosphorylated-Smad2/3 protein. Furthermore, pretreatment with TGF-beta 1
      neutralizing antibody suppressed chymase-induced cell growth, collagen
      production, and Smad activation. In contrast, the blockade of angiotensin II
      receptor had no effects on chymase-induced production of TGF-beta 1 and
      profibrotic action. Additionally, the inhibition of MAPK signaling had no effect
      on Smad activation elicited by chymase. These results suggest that chymase can
      promote CFs proliferation and collagen synthesis via TGF-beta 1/Smad pathway
      rather than angiotensin II, which is implicated in the process of MF.

PMID- 18057998
TI  - Na+/H+ exchange inhibition with cariporide prevents alterations of coronary
      endothelial function in streptozotocin-induced diabetes.
AB  - Hyperglycemia encountered during diabetes triggers abnormalities of vascular
      function associated with cell acidosis and calcium overload. The purpose of this
      study was to determine, whether Na+/H+ exchanger (NHE-1) inhibition by cariporide
      protects coronary cells against the deleterious effect of hyperglycemia in the
      rat. In vivo hyperglycemia was triggered by streptozotocin injection. One week
      after, the glycemia was checked and the control and diabetic animals were treated
      or not with cariporide (2.5 mg/kg/day) for two weeks. Glycemia was again
      estimated and the hearts were perfused according to the Langendorff mode at
      forced flow. The left ventricle developed pressure (LVDP) and heart rate (HR)
      were determined with a latex balloon inserted into the left ventricle. Coronary
      pressure was artificially increased to 130 mmHg by infusing a thromboxane A2
      analogue (U46619). This allowed the evaluation of endothelium-dependent (EDD) and
      endothelium-independent (EID) dilatation through bolus injections of
      carbamoylcholin and sodium nitroprusside, respectively. Releases of lactate and
      pyruvate in the coronary effluents were also determined. Diabetes did not
      modified LVDP, but reduced HR (-15%). This was associated with a marked decrease
      in EDD (-56%) and EID (-30%), while the cytosolic redox potential (estimated as
      the lactate/pyruvate ratio) was reduced. NHE-1 inhibition restored EDD and the
      lactate/pyruvate ratio without improving EID and HR. The present findings
      indicate that NHE-1 exchanger inhibition by cariporide protects the coronary
      endothelium against the deleterious effects of hyperglycemia.

PMID- 18057999
TI  - Involvement of p38 MAPK-mediated signaling in the calpeptin-mediated suppression
      of myogenic differentiation and fusion in C2C12 cells.
AB  - Calpeptin inhibits myoblast fusion by inhibiting the activity of calpain.
      However, the mechanism by which calpeptin inhibits myogenesis is not completely
      understood. This study examined how calpeptin affects the expression of the
      myogenic regulatory factors (MRFs) and the phosphorylation of p38 mitogen
      activated protein kinase (MAPK) in differentiating C2C12 myoblasts. Consistent
      with previous reports, calpeptin inhibited the induction of mu-calpain and the
      formation of myotubes in these cells. In particular, calpeptin inhibited the
      expression of the early and mid differentiation markers including MyoD, Myf5,
      myogenin, and MRF4 as well as the expression of the late markers such as troponin
      T and myosin heavy chain (MyHC). Calpeptin also suppressed the phosphorylation of
      p38 MAPK in C2C12 cells. SB203580, a specific p38 inhibitor, prevented the
      expression of the muscle-specific markers and their fusion into myotubes in these
      cells, which was further accelerated in the presence of calpeptin. These findings
      suggest that calpeptin inhibits the myogenesis of skeletal muscle cells by down
      regulating the MRFs and involving p38 MAPK signaling.

PMID- 18058000
TI  - Water sorption/desorption in polyacid-modified composite resins for dentistry.
AB  - The water sorption and desorption behaviour of three commercial polyacid-modified
      composite resins used in clinical dentistry have been studied in detail. Cured
      specimens of each material were subjected to two successive water uptake cycles
      in an atmosphere of 93% relative humidity, with one intervening desorption cycle
      in a desiccating atmosphere over concentrated sulfuric acid. Specimens were found
      to absorb and desorb water according Fick's law until Mt/M(infinity) values of
      approximately 0.5. Diffusion rates for uptake varied between cycles, ranging from
      2.37-4.53 x 10(-9 )cm(2) s(-1) for 1st cycle to 0.85-2.72 x 10(-8 )cm(2 )s(-1)
      for 2nd cycle. Desorption rates were similar to those for 2nd cycle sorption, and
      ranged from 0.86 to 5.47 x 10(-8 )cm(2 )s(-1). Equilibration times for 1st cycle
      water uptake were greater than for 2nd cycle sorption and for desorption and
      overall the behaviour of polyacid-modified composites in a high humidity
      atmosphere was similar to that of conventional composites in water. It is
      concluded that the hydrophilic components of the former do not bring about an
      enhanced rate of water transport.

PMID- 18058001
TI  - Safe and effective permeation enhancers for oral drug delivery.
AB  - PURPOSE: The use of intestinal permeation enhancers to overcome the absorption
      challenges associated with oral drug delivery has been hampered by the notion
      that enhancer efficacy is directly linked to toxicity. This study attempts to
      gain insight into the principles governing the potency and toxicity behavior of
      enhancers. METHODS: Fifty-one enhancers were selected from 11 chemical categories
      and their potency and toxicity were analyzed in Caco-2 monolayers at
      concentrations spanning three orders of magnitude. RESULTS: A small but
      significant fraction of the 153 enhancer formulations studied demonstrated
      unexpected but desired behavior, that is, substantial efficacy without marked
      toxicity. Our results revealed that both chemical category and concentration
      proved critical in determining the usefulness of many enhancers, and the concept
      of an enhancer's 'therapeutic window' is discussed. Several of the most promising
      enhancers identified by the study were tested for their effect on the transport
      of the marker molecules mannitol and 70 kDa dextran across Caco-2 cells and were
      capable of increasing permeability more than 10-fold. CONCLUSIONS: The results
      presented here underscore the potential of chemical permeation enhancers while
      providing valuable direction as to what classes and concentrations of compounds
      are of interest when searching for safe and effective additions to oral
      formulations.

PMID- 18058002
TI  - Governing humanity.
AB  - In the United Kingdom, clinical governance has become a master narrative for
      health care over the last decade. While many see this political imperative as
      embodying both enlightening and humanistic goals, I argue that it has also become
      an apparatus for resuscitating a hypermodernist worldview which further conceals
      the political drivers of health care delivery. While resistance to clinical
      governance seems futile, insistence on the inclusion of historical analysis in
      understanding modern health care delivery may be profitable. Drawing from
      selected dramatic texts by Henrik Ibsen, an historical moment of clinical
      governance may be analysed showing the complex interplay of the personal, social,
      empirical and ethical dimensions of health care delivery.

PMID- 18058003
TI  - Rejecting medical humanism: medical humanities and the metaphysics of medicine.
AB  - The call for a narrative medicine has been touted as the cure-all for an
      increasingly mechanical medicine. It has been claimed that the humanities might
      create more empathic, reflective, professional and trustworthy doctors. In other
      words, we can once again humanise medicine through the addition of humanities. In
      this essay, I explore how the humanities, particularly narrative medicine,
      appeals to the metaphysical commitments of the medical institution in order to
      find its justification, and in so doing, perpetuates a dualism of humanity that
      would have humanism as the counterpoint to the biopsychosociologisms of our day.

PMID- 18058004
TI  - Abundance of Escherichia coli F1-ATPase molecules observed to rotate via single
      molecule microscopy with gold nanorod probes.
AB  - The abundance of E. coli F1-ATPase molecules observed to rotate using gold
      nanorods attached to the gamma-subunit was quantitated. Individual F1 molecules
      were determined to be rotating based upon time dependent fluctuations of red and
      green light scattered from the nanorods when viewed through a polarizing filter.
      The average number of F1 molecules observed to rotate in the presence of GTP,
      ATP, and without nucleotide was approximately 50, approximately 25, and
      approximately 4% respectively. In some experiments, the fraction of molecules
      observed to rotate in the presence of GTP was as high as 65%. These data indicate
      that rotational measurements made using gold nanorods provide information of the
      F1-ATPase mechanism that is representative of the characteristics of the enzyme
      population as a whole.

PMID- 18058005
TI  - The K+-translocating KdpFABC complex from Escherichia coli: a P-type ATPase with
      unique features.
AB  - The prokaryotic KdpFABC complex from the enterobacterium Escherichia coli
      represents a unique type of P-type ATPase composed of four different subunits, in
      which a catalytically active P-type ATPase has evolutionary recruited a potassium
      channel module in order to facilitate ATP-driven potassium transport into the
      bacterial cell against steep concentration gradients. This unusual composition
      entails special features with respect to other P-type ATPases, for example the
      spatial separation of the sites of ATP hydrolysis and substrate transport on two
      different polypeptides within this multisubunit enzyme complex, which, in turn,
      leads to an interesting coupling mechanism. As all other P-type ATPases, also the
      KdpFABC complex cycles between the so-called E1 and E2 states during catalysis,
      each of which comprises different structural properties together with different
      binding affinities for both ATP and the transport substrate. Distinct
      configurations of this transport cycle have recently been visualized in the
      working enzyme. All typical features of P-type ATPases are attributed to the KdpB
      subunit, which also comprises strong structural homologies to other P-type ATPase
      family members. However, the translocation of the transport substrate, potassium,
      is mediated by the KdpA subunit, which comprises structural as well as functional
      homologies to MPM-type potassium channels like KcsA from Streptomyces lividans.
      Subunit KdpC has long been thought to exhibit an FXYD protein-like function in
      the regulation of KdpFABC activity. However, our latest results are in favor of
      the notion that KdpC might act as a catalytical chaperone, which cooperatively
      interacts with the nucleotide to be hydrolyzed and, thus, increases the rather
      untypical weak nucleotide binding affinity of the KdpB nucleotide binding domain.

PMID- 18058006
TI  - Plasmalemmal vacuolar H+-ATPases in angiogenesis, diabetes and cancer.
AB  - Angiogenesis, i.e., new blood vessel formation, is required in normal and
      pathological states. A dysfunction in the microvascular endothelium occurs in
      diabetes, leading to decreased blood flow and limb amputation. In cancer,
      angiogenesis is increased to allow for growth, invasion, and metastasis of tumor
      cells. Better understanding of the molecular events that cause or are associated
      with either of these diseases is needed to develop therapies. The tumor and
      angiogenic cells micro-environment is acidic and not permissive for growth. We
      have shown that to survive this environment, highly metastatic and angiogenic
      cells employ vacuolar H+-ATPase at their plasma membranes (pmV-ATPases) to
      maintain an alkaline pHcyt. However, in lowly metastatic and in microvascular
      endothelial cells from diabetic model, the density of pmV-ATPase and the cell
      invasiveness are decreased. Therefore, the overexpression of the pmV-ATPase is
      important for cell invasion, and essential for tumor progression, angiogenesis
      and metastasis. Both, cancer and diabetes are heterogenous diseases that involve
      many different proteins and signaling pathways. Changes in pHcyt have been
      associated with the regulation of a myriad of proteins, signaling molecules and
      pathways affecting many if not all cellular functions. Since changes in pHcyt are
      pleiotropic, we hypothesize that alteration in a single protein, pmV-ATPase, that
      can regulate pHcyt may explain the dysfunction of many proteins and cellular
      pathways in diabetes and cancer. Our long term goal is to determine the molecular
      mechanisms by which pmV-ATPase expression regulates tumor angiogenesis and
      metastasis. Such knowledge would be useful to identify targets for cancer
      therapy.

PMID- 18058008
TI  - Activation of protease activated receptor-2 induces delayed cardioprotection in
      anesthetized mice.

PMID- 18058007
TI  - Roles of transmembrane segment M1 of Na+,K+-ATPase and Ca2-ATPase, the gatekeeper
      and the pivot.
AB  - In this review we summarize mutagenesis work on the structure-function
      relationship of transmembrane segment M1 in the Na+,K+-ATPase and the
      sarco(endo)plasmic reticulum Ca2+-ATPase. The original hypothesis that charged
      residues in the N-terminal part of M1 interact with the transported cations can
      be rejected. On the other hand hydrophobic residues in the middle part of M1
      turned out to play crucial roles in Ca2+ interaction/occlusion in Ca2+-ATPase and
      K+ interaction/occlusion in Na+,K+-ATPase. Leu65 of the Ca2+-ATPase and Leu99 of
      the Na+,K+-ATPase, located at homologous positions in M1, function as gate
      locking residues that restrict the mobility of the side chain of the cation
      binding/gating residue of transmembrane segment M4, Glu309/Glu329. A pivot formed
      between a pair of a glycine and a bulky residue in M1 and M3 seems critical to
      the opening of the extracytoplasmic gate in both the Ca2+-ATPase and the Na+,K+
      ATPase.

PMID- 18058009
TI  - A psychophysical test of the visual pathway of children with autism.
AB  - Signal detection psychophysical experiments were conducted to investigate the
      visual path of children with autism. Computer generated images with Gaussian
      noise were used. Simple signals, still and in motion were embedded in the
      background noise. The computer monitor was linearized to properly display the
      contrast changes. To our knowledge, this is the first time that experiments of
      this type have been done with observers with autism. Our results show that the
      visual capabilities of typically developed children were superior to those of the
      children with autism, and that the related problems of children with autism are
      sensation related only in a reduced proportion. There is no evidence that they
      are disabled in detecting simple visual stimuli, still and in motion.

PMID- 18058010
TI  - Use of home videotapes to confirm parental reports of regression in autism.
AB  - The current study examined consistency between parental reports on early language
      development and behaviors in non-language domains and observer-coded videotapes
      of young children with and without autism spectrum disorder (ASD) and autistic
      regression. Data are reported on 56 children (84% male) with ASD (early onset or
      autistic regression) and 14 typically developing children (57% male) who had home
      videotapes. Unique to the current study is the independent identification of
      loss/no loss for each child by both parental report and observer-coded home
      videotapes and the examination of agreement between these two methods. Results
      indicate substantial concordance between parental report and observer codes for
      onset and loss of expressive language, but minimal concordance for loss in non
      language domains, suggesting a need for supplementation of parental reports in
      these areas.

PMID- 18058011
TI  - Head circumference as an early predictor of autism symptoms in younger siblings
      of children with autism spectrum disorder.
AB  - Siblings of children with autism have an increased risk for autism spectrum
      disorders (ASD). As children with autism often exhibit an atypical trajectory of
      head circumference (HC) growth, HC may be an indicator of vulnerability to
      autism. This study investigated whether infant siblings of children with ASD (n =
      77) with an atypical trajectory of HC growth were more likely than those without
      an atypical HC trajectory to develop autism symptoms. Results showed that infants
      who had larger HC at 12 months, and whose HC growth rate decelerated more rapidly
      between 12 and 24 months were more likely to exhibit autism symptoms than infants
      with more typical HC trajectories. Among infant siblings of children with autism,
      atypical HC growth might alert pediatricians to provide screening and/or referral
      for further evaluation.

PMID- 18058012
TI  - Effectiveness of a manualized summer social treatment program for high
      functioning children with autism spectrum disorders.
AB  - This paper presents findings from the final two years of a four-year study
      investigating a manualized social treatment program for high-functioning children
      with autism spectrum disorders. The study sought to (1) replicate and expand
      findings from years one and two; (2) compare outcomes of participants who
      received response-cost feedback versus non-categorical feedback; and (3) provide
      further evidence of program feasibility. Results indicated significant
      improvements in social skills and problem behaviors, however no significant
      differences for face emotion recognition. Measures of several socially-related
      behaviors yielded mixed results based on rater. While parent ratings did not
      appear to favor one feedback format, staff ratings appeared to favor the response
      cost format on some measures. Results also provided support for program
      feasibility.

PMID- 18058013
TI  - Molecular characterization and evolutionary analysis of soybean mosaic virus
      infecting Pinellia ternata in China.
AB  - Twenty-nine Pinellia ternata specimens were collected from representative areas
      in China, including the major production provinces of Zhejiang, Henan, Shanxi,
      Hunan, Shandong and Hubei. Seven isolates related to soybean mosaic virus (SMV),
      which could be pathogenic on P. ternata and some soybean [Glycine max (L.) Merr.]
      cultivars, were detected using double antibody sandwich immunosorbent assay (DAS
      ELISA) and RT-PCR amplification performed with degenerate primer of potyviruses.
      It is revealed that the common potyvirus infecting P. ternata is, indeed, only
      SMVs rather than Dasheen mosaic virus (DsMV) as previously reported. Further
      molecular phylogenetic analysis of the coat protein (CP) genes of these SMV
      isolates from P. ternata and G. max, along with some other potyvirus members,
      such as DsMV and Watermelon mosaic virus (WMV) reconstructed the evolutionary
      route on both nucleotide and amino acid levels. Similarity and homology of
      nucleotide sequences for SMV CP genes demonstrated high host correlation and low
      partial habitat correlation, while those of amino acid sequences also showed that
      the host correlation was more notable than the habitat correlation. The amino
      acid sequence of conserved region within CP determines the main function, which
      shows high homology between species. This study outspreaded from the viruses
      themselves and their relationship to the infected hosts and revealed the
      evolutionary strategies, especially the rapid variation or recombination of SMV
      of P. ternata, in order to adapt itself naturally to the special host.

PMID- 18058014
TI  - Increase in Chlamydia trachomatis infection in Sweden: time for new strategies.

PMID- 18058016
TI  - Mild ovarian stimulation.
AB  - PURPOSE: To evaluate the efficacy of using only mild ovarian stimulation
      protocols for in vitro fertilization. Both groups with decreased and normal
      ovarian reserve were evaluated. METHODS: Three different mild stimulation
      protocols were evaluated: natural with no exogenous follicle stimulation hormone
      (FSH) drugs at all, natural with a boost of low dose FSH to complete follicular
      maturation, and minimal stimulation with low dose (75-150IU) FSH from day 3-5 of
      the menstrual cycle. Ethinyl estradiol was sometimes used to lower high day 3
      serum FSH. RESULTS: Good pregnancy and implantation rates were found even in
      those women with elevated serum FSH that could only generate one follicle.
      CONCLUSIONS: Mild ovarian stimulation seems preferable to high dose FSH regimens
      in women with elevated day 3 serum FSH based on previous poor reported pregnancy
      rates with the latter protocols. Comparable pregnancy rates to high dose regimen
      were seen in women with normal egg reserve at much lower risk and cost.

PMID- 18058017
TI  - Time course of peripheral oxidative stress as consequence of global ischaemic
      brain injury in rats.
AB  - Free radicals play an important role in the pathogenesis of brain injury. This
      study evaluates the potential relationship between ischaemia/reperfusion (I/R)
      induced brain injury, peripheral oxidative stress (lymphocyte DNA damage), plasma
      antioxidant potential and uric acid levels. We observed that 15 min of ischaemia
      were sufficient to significantly increase lymphocyte DNA damage that remained
      elevated at the end of early (3 h) reperfusion and at later (72 h) reperfusion
      time; this parameter was not significantly increased, when compared to
      preoperated levels. In parallel, antioxidant potential was elevated after 15 min
      of ischaemia, remained high at early (3 h) reperfusion and decreased again with
      longer (72 h) reperfusion. A close association between the plasma antioxidant
      status and the uric acid content has been confirmed by findings that changes in
      TRAP values positively correlate with uric acid concentration in rat plasma after
      ischaemic injury. Moreover, results of in vitro experiments with extra uric acid
      addition to control plasma have shown that uric acid contributes to a greater
      part of TRAP values. These results indicate a similar time course of brain I/R
      associated oxidative stress and peripheral antioxidant defence status and/or
      oxidative stress in animal experiments.

PMID- 18058018
TI  - The Neuroscience Research Institute at Peking University: a place for the
      solution of pain and drug abuse.
AB  - Neuroscience research in China has undergone rapid expansion since 1980. The
      Neuroscience Research Institute of Peking University, one of the most active
      neuroscience research groups in China, was founded in 1987. Currently, the
      institute is overseeing four research areas, i.e., (1) pain and analgesia, (2)
      drug abuse and acupuncture treatment for drug addiction, (3) the mechanism of
      neurological degenerative disorders, and (4) the role of neuroglia in central
      nervous system injury. The institute is simultaneously investigating both
      theoretical and clinical studies. Acupuncture remains the core of research, while
      pain and drug abuse form the two disciplines.

PMID- 18058019
TI  - Objective versus subjective assessment of methylphenidate response.
AB  - Subjective improvement-assessment in attention deficit/hyperactivity disorder
      (ADHD), following a single dose of methylphenidate (MPH) was compared to
      performance on the Test-of-Variables-of-Attention (TOVA). Self-perception was
      assessed with the clinical-global-impression-of-change (CGI-C). Participants
      included 165 ADHD subjects (M:F ratio 67%:33%) aged 5-18 (11.09 +/- 3.43) years.
      TOVA was administered before and after MPH challenge (0.3 mg/kg). Self-perception
      CGI-C scores were compared to the TOVA scores. An inverse correlation was found
      only between CGI-C and the TOVA-Commission-scores (r = -0.326, p < 0.001). We
      thus conclude that subjective reports are too unreliable to be used in order to
      assess MPH benefit in ADHD pediatric populations.

PMID- 18058021
TI  - Receding horizon controller for the baroreceptor loop in a model for the
      cardiovascular system.
AB  - In this article, we discuss the design and implementation of a receding horizon
      control (RHC) which will be used to represent the control for the baroreceptor
      loop in the human cardiovascular system (CVS). This control will be applied to a
      model of the CVS developed in a previous work by Kappel and Peer. In that earlier
      work, a linear quadratic control strategy (LQR) was implemented to represent this
      baroreflex control which was designed to stabilize the system under an ergometric
      workload. The RHC approach will be examined as an alternate to the LQR
      implementation. The control parameters in the cost functional of the RHC will be
      estimated using the same experimental data as was used in the LQR study. The
      results of the RHQ implementation will be compared with the LQR implementation.

PMID- 18058020
TI  - Dietary fiber is associated with serum sex hormones and insulin-related peptides
      in postmenopausal breast cancer survivors.
AB  - OBJECTIVE: To measure the association between dietary fiber intake and eleven
      hormones and peptides in postmenopausal breast cancer survivors. METHODS: Intake
      of fiber from food and supplements was measured two to three years after breast
      cancer diagnosis in 493 postmenopausal women from three western states.
      Concurrently, a fasting blood sample was obtained for assay of estrone,
      estradiol, free estradiol, testosterone, free testosterone,
      dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), leptin, C
      peptide, insulin-like growth factor-1 (IGF1), and IGF-binding protein-3. Adjusted
      means of these hormones and peptides were calculated for categories of fiber
      intake. RESULTS: High intake of dietary fiber was significantly (P<or=0.05)
      associated with low serum levels of estradiol and free estradiol and with high
      serum levels of IGF1. The combination of high dietary fiber intake and use of
      fiber supplements was additionally associated with low serum levels of C-peptide.
      The magnitude of the difference in hormone/peptide values, comparing high fiber
      intake to low fiber intake, varied from 16 to 28%, and the associations were
      independent of multiple confounding variables. CONCLUSION: High fiber diets may
      be beneficial to postmenopausal breast cancer survivors due to fiber's favorable
      influence on sex hormones and peptides known to affect breast cancer prognosis.

PMID- 18058023
TI  - Phonological processing and emergent literacy in younger and older preschool
      children.
AB  - Phonological awareness, phonological memory, and phonological access to lexical
      storage play important roles in acquiring literacy. We examined the convergent,
      discriminant, and predictive validity of these phonological processing abilities
      (PPA) in 389 3-, 4-, and 5-year-old children. Confirmatory factor analysis
      supported the validity of each PPA as separate from general cognitive ability and
      separate from each other. Multigroup structural equation modeling (SEM) with mean
      structure demonstrated that older preschoolers have better developed latent PPA
      than younger preschoolers but that the structure of PPA is equivalent. RAN was
      found uniquely associated with letter knowledge and text discrimination in
      younger preschoolers, and PA was found uniquely associated with word reading
      skills in older preschoolers. Finally, general cognitive ability was only
      indirectly associated with emergent literacy via PPA. These results highlight the
      importance of PPA in the early literacy development of English-speaking preschool
      children.

PMID- 18058024
TI  - Element mobility and partitioning along a soil acidity gradient in central
      Ontario forests, Canada.
AB  - The potential environmental risk posed by metals in forest soils is typically
      evaluated by modeling metal mobility using soil-solution partitioning
      coefficients (K(d)), although such information is generally restricted to a few
      well-studied metals. Soil-solution partitioning coefficients were determined for
      17 mineral elements (Al, As, Be, Ba, Ca, Cr, Cu, Fe, Ga, K, Li, Mg, Rb, Sr, Tl, U
      and V) in A-horizon (0-5 cm) soil at 46 forested sites that border the
      Precambrian Shield in central Ontario, where soil pH(aq) varied from 3.9 to 8.1.
      Sites were dominated by mature sugar maple (Acer saccharum Marsh.), white birch
      (Betula papyrifera Marsh.), balsam fir (Abies balsamea (L.) Mill.) or white pine
      (Pinus strobus L.). Log K(d) values for all elements could be predicted by
      empirical linear regression with soil pH (r(2) = 0.17-0.77) independent of forest
      type, although this relationship was greatly affected by positive relationships
      between acid-extractable metal concentration and pH(aq) for 13 of the 17
      elements. Elements that exhibited strong or moderate (r(2) > 0.29; p < 0.001)
      relationships with soil pH(aq) in soil water extracts include Al, Ba, Fe, Ga, K,
      Li, Rb, Tl, V (negative) and Ca (positive). Elemental partitioning in mineral
      soil was independent of forest type; tree species differed in their response to
      chemical differences in mineral soil. For example, Rb, Ba, and Sr concentrations
      in foliage of sugar maple and white birch significantly increased with increasing
      soil acidity, whereas Rb, Ba, and Sr concentrations in balsam fir and white pine
      foliage exhibited no response to soil pH(aq). While K(d) values can provide
      useful information on the potential mobility and bioavailability of mineral
      elements in forest soils, care must be used when interpreting the relative
      contribution of solid and aqueous phases to this relationship and the differing
      responses of vegetation in elemental cycling in forests must also be considered.

PMID- 18058025
TI  - Rearing of coconut mite Aceria guerreronis and the predatory mite Neoseiulus
      baraki in the laboratory.
AB  - A method was developed for the rearing of coconut mite, Aceria guerreronis Keifer
      (Acari: Eriophyidae), and its predatory mite Neoseiulus baraki (Athias-Henriot)
      (Acari: Phytoseiidae) on embryo culture seedlings of coconut (Cocos nucifera) in
      the laboratory. Seedlings in the ages of <2, 2-4 and 4-6 months were infested
      with 75 field-collected coconut mites and the population growth was determined up
      to six weeks after introduction. The populations of coconut mites increased
      exponentially up to five weeks after introduction and declined thereafter on
      seedlings of all ages with significant differences among the three groups of
      seedlings occurring over time. At week 5, a significantly higher mean number (+/
      SE) of coconut mites (20,098 +/- 3,465) was bred on 4-6-month-old seedlings than
      on smaller seedlings, and on the largest seedlings the numbers were highest at
      all time intervals, except at week 2. Neoseiulus baraki was reared on embryo
      culture seedlings of the three age groups infested with coconut mites, by
      introduction of five female deutonymphs and one male, three weeks after
      introducing coconut mites. Predator numbers progressed significantly over time,
      but the size of seedlings did not significantly influence the numbers. On all
      groups of seedlings, the mean number of N. baraki increased up to two weeks after
      introduction on to seedlings and then declined. Many coconut mites were
      successfully reared in the laboratory for a longer period by this method and it
      could also be used as an alternative method to rear N. baraki. Development of
      this method may contribute to the progress of studies on the biology and ecology
      of coconut mite and its interactions with natural enemies.

PMID- 18058026
TI  - Life history of the predatory mite Phytoseiulus fragariae on Tetranychus evansi
      and Tetranychus urticae (Acari: Phytoseiidae, Tetranychidae) at five
      temperatures.
AB  - Tetranychus evansi Baker and Pritchard and Tetranychus urticae Koch (Acari:
      Tetranychidae) are important pests of Solanaceae in many countries. Several
      studies have demonstrated that T. urticae is an acceptable prey to many predatory
      mites, although the suitability of this prey depends on the host plant. T.
      evansi, has been shown to be an unfavorable prey to most predatory mites that
      have been tested against it. The predator Phytoseiulus fragariae Denmark and
      Schicha (Acari: Phytoseiidae) has been found in association with the two species
      in Brazil. The objective of this work was to compare biological parameters of P.
      fragariae on T. evansi and on T. urticae as prey. The study was conducted under
      laboratory conditions at 10, 15, 20, 25 and 30 degrees C. At all temperatures,
      survivorship was lower on T. evansi than on T. urticae. No predator reached
      adulthood at 10 degrees C on the former species; even on the latter species, only
      about 36% of the predators reached adulthood at 10 degrees C. For both prey, in
      general, duration of each life stage was shorter, total fecundity was lower and
      intrinsic rate of population increase (r(m)) was higher with increasing
      temperatures. The slower rate of development of P. fragariae on T. evansi
      resulted in a slightly higher thermal requirement (103.9 degree-days) on that
      prey than on T. urticae (97.1 degree-days). The values of net reproduction rate
      (R (0)), intrinsic rate of increase (r(m)) and finite rate of increase (lambda)
      were significantly higher on T. urticae, indicating faster population increase of
      the predator on this prey species. The highest value of r(m) of the predator was
      0.154 and 0.337 female per female per day on T. evansi and on T. urticae,
      respectively. The results suggested that P. fragariae cannot be considered a good
      predator of T. evansi.

PMID- 18058028
TI  - Reversing mitochondrial dysfunction, fatigue and the adverse effects of
      chemotherapy of metastatic disease by molecular replacement therapy.
AB  - Metastatic cancers are associated with cellular oxidative stress, and during
      cancer chemotherapy excess drug-induced oxidative stress can limit therapeutic
      effectiveness and cause a number of side effects, including fatigue, nausea,
      vomiting, diarrhea and more serious adverse effects, such as cardiomyopathy,
      peripheral neuropathy, hepatotoxicity and pulmonary fibrosis. We review here the
      hypothesis that the acute and chronic adverse effects of cancer chemotherapy can
      be reduced by molecular replacement of membrane lipids and enzymatic cofactors,
      such as coenzyme Q(10). By administering nutritional supplements with replacement
      molecules and antioxidants, oxidative membrane damage and reductions of cofactors
      in normal tissues can be reversed, protecting and restoring mitochondrial and
      other cellular functions and reducing chemotherapy adverse effects. Recent
      clinical trials using cancer and non-cancer patients with chronic fatigue have
      shown the benefit of molecular replacement plus antioxidants in reducing the
      damage to mitochondrial membranes, restoring mitochondrial electron transport
      function, reducing fatigue and protecting cellular structures and enzymes from
      oxidative damage. Molecular replacement and antioxidant administration mitigates
      the damage to normal tissues, such as cardiac tissue, and reduces the adverse
      effects of cancer therapy without reduction in therapeutic results.

PMID- 18058027
TI  - The tumor cell-host organ interface in the early onset of metastatic organ
      colonisation.
AB  - Metastatic lesions are the leading cause of death among cancer patients. These
      lesions usually originate from clonal proliferation of single tumor cells
      dispersed from the primary tumor into the circulation which finally arrest in the
      capillary bed of distant organs. The microenvironment within the circulation of
      potential metastatic target organs provides a variety of pro- and anti-
      metastatic stimuli regulating the onset of organ colonisation by metastatic tumor
      cells. Mechanical shear stress, anoikis and cell mediated cytotoxicity within the
      microcirculation probably clear most circulating tumor cells. Adhesion, and
      eventually extravasation, are essential initial interactions of circulating tumor
      cells with distant organs and can provide escape from the cytotoxic environment
      within the circulation. Adhesion to the capillary wall is mostly controlled by
      the organ-specific availability of adhesion molecules on tumor cells, the
      endothelium, and the composition of the underlying extracellular matrix. The
      availability of pro-adhesive and pro-migratory paracrine signals provided by the
      organ specific microenvironment can further initiate the onset of metastatic
      organ colonisation. Tumor cell and microenvironment factors regulating survival
      within the microcirculation, adhesion and extravasation of tumor cells are
      highlighted in the review.

PMID- 18058029
TI  - Nm23-H1 homologs suppress tumor cell motility and anchorage independent growth.
AB  - Nm23-H1 suppresses metastasis, as well as in vitro cell motility, invasion and
      anchorage independent growth, in a variety of cancer models. Eight human homologs
      of Nm23 have been identified that share 26-88% identity with the prototype Nm23
      H1. Here, we examine the potential of its homologs, -H2, DR-, -H4 and -H5, to
      inhibit in vitro correlates of metastasis in two highly metastatic human cell
      lines, MDA-MB-435 and MDA-MB-231. The metastatic cells were transfected with
      mammalian expression constructs containing the genes encoding for Nm23-H1, -H2,
      DR-, -H4 and -H5 and the resultant transfectants were analyzed by Boyden chamber
      motility and soft agar colonization assays. Nm23-H1 suppressed motility by 3.3-
      and 1.5-fold in MDA-MB-435 and MDA-MB-231 cells, respectively and inhibited
      anchorage independent growth in soft agar by 2.9- and 1.9-fold, respectively.
      None of the -H1 homologs were capable of suppressing motility in MDA-MB-435
      cells, but in MDA-MB-231 cells, -H2 inhibited motility by 3-fold upon
      overexpression. When anchorage independent growth was assessed, -H2, -H4 and -H5
      suppressed growth from 1.2- to 2.0-fold in both cell lines. Given their ability
      to suppress anchorage independent growth, Nm23-H1 homologs -H2, -H4 and -H5 may
      have some capacity to suppress metastasis. Motility suppression appears to be
      cell context dependent, but sequence disparities between -H1/H2 and the other
      family members may reveal regions critical for this inhibitory phenotype.
      Similarly, sequence differences between DR-Nm23 and its homologs may be important
      for anchorage independent growth suppression.

PMID- 18058031
TI  - Comet assay-based methods for measuring DNA repair in vitro; estimates of inter-
      and intra-individual variation.
AB  - DNA repair is one of the important determinants of susceptibility to cancer. It
      is therefore useful to be able to measure DNA repair capacity in samples from
      population studies. Our aim was, first, to develop a simple comet-based in vitro
      assay for nucleotide excision repair (NER), similar to that already in use for
      base excision repair (BER), and then to apply these in vitro assays to lymphocyte
      samples collected on several occasions from healthy subjects, to gain an
      impression of the degree of intra- and inter-individual variability. The in vitro
      assay consists of an incubation of lymphocyte extract with substrate nucleoid DNA
      from cells pretreated with specific damaging agent; either photosensitiser plus
      light to induce 8-oxoguanine, for BER, or short wavelength ultraviolet light
      irradiation for NER. In the new NER assay, which requires magnesium but not
      adenosine triphosphate, there was significant accumulation of UV-dependent
      incisions during a 30-min incubation of extract with DNA. We found significant
      correlations between individual repair rates from samples taken on different
      occasions; i.e. individuals have a characteristic repair capacity. There was also
      significant variation between individuals, to the extent of about fourfold for
      BER and tenfold for NER. There was no correlation between BER and NER rates. The
      BER and NER assays are simple to perform and can provide valuable information in
      molecular epidemiological studies in which DNA instability is an endpoint.

PMID- 18058030
TI  - Analyses of the role of endogenous SPARC in mouse models of prostate and breast
      cancer.
AB  - Secreted protein, acidic and rich in cysteine (SPARC, also known as osteonectin
      or BM-40) is a glycoprotein component of the extracellular matrix that has been
      reported to be involved with a variety of cellular processes. Although SPARC
      expression levels are frequently altered in a variety of tumor types, the exact
      implications of deregulated SPARC expression--whether it promotes, inhibits or
      has no effect on tumor progression--have remained unclear. Our recent gene
      expression analyses have shown that SPARC is significantly downregulated in
      highly metastatic human prostate cancer cells. To test the role of endogenous
      SPARC in tumorigenesis directly, we examined cancer progression and metastasis in
      SPARC(+/-) and SPARC(-/-) mice using two separate transgenic mouse tumor models:
      transgenic adenocarcinoma of the mouse prostate (TRAMP) and murine mammary tumor
      virus-polyoma middle T (MMTV-PyMT). Surprisingly, in both instances, we found
      that loss of SPARC had no significant effects on tumor initiation, progression or
      metastasis. Tumor angiogenesis and collagen deposition were also largely
      unaffected. Our results indicate that, although differential SPARC expression may
      be a useful marker of aggressive, metastasis-prone tumors, loss of SPARC is not
      sufficient either to promote or to inhibit cancer progression in two spontaneous
      mouse tumor models.

PMID- 18058032
TI  - Spring-harvested game birds in the Western James Bay region of Northern Ontario,
      Canada: the amount of organochlorines in matched samples of breast muscle, skin,
      and abdominal fat.
AB  - We examined matched-tissue samples (the right pectoral muscle plus the associated
      skin and fat was considered a breast portion) of 81 spring-harvested waterfowl
      and 19 summer-harvested godwits (Limosa spp.) to assess the potential of these
      water birds contributing to the body burden of PCBs and DDT noted in First Nation
      people of the western James Bay region, northern Ontario, Canada. In general, the
      dabbling ducks (mallard duck, Anas platyrhynchos; and northern pintail, A. acuta)
      had significantly lower percent lipid (gravimetrically determined) values in skin
      tissue, fat tissue, and breast muscle compared to the goose species (Canada
      goose, Branta canadensis; lesser snow goose, Chen caerulescens); godwits had
      percent lipid values not significantly different than ducks and geese. Also, the
      percent lipid values in skin for all species of birds examined approached those
      found in fat tissue. Organochlorine data were expressed as the amount (microg) of
      each contaminant per breast portion to show contaminant consumption in terms of
      typical and easily recognizable dietary portions; direct comparisons were made to
      acceptable daily intake (ADI) or tolerable daily intake (TDI) values as
      recommended by Health Canada. Significant differences in the amount of
      organochlorines between bird species for skin, fat tissue, and breast muscle
      samples were found. In general, breast portions from snow geese contained the
      least amount of organochlorines, followed by godwits (except for mirex) and then
      Canada geese; the dabbling ducks had the greatest amount of organochlorines on a
      breast portion basis. However, on average, no 60 kg person would exceed the
      calculated organochlorine ADI/TDI values consuming one breast portion (i.e.,
      breast + associated skin and fat), but the maximum value of SigmaPCBs for skin
      tissue alone in male mallards (47 microg) was more than twice the ADI/TDI (18
      microg/day); while, that in fat tissue alone (17 microg) approached the ADI/TDI.
      Thus, the consumption of dabbling ducks by children is an issue that should be
      explored further, if tissue other than breast muscle is eaten. Lastly, the
      consumption of waterfowl was a source of PCBs for people of Fort Albany and
      Kashechewan, but not DDT, as this organochlorine was infrequently detected.

PMID- 18058033
TI  - Monitoring pollution in Esmoriz-Paramos lagoon, Portugal: liver histological and
      biochemical effects in Liza saliens.
AB  - The Esmoriz-Paramos lagoon is one important ecosystem located in the Northwest
      coast of Portugal. This study is concerned with the assessment of pollution of
      the lagoon contributed by urban, industrial and agricultural activities. The
      parameters selected for this aim were the occurrence of hepatic histological
      alterations and plasma blood biochemistry in Liza saliens, the dominant fish in
      this lagoon. Blood parameters were compared between mullets collected from the
      lagoon and from the sea and included plasma enzyme activities (aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase
      (ALP)), glucose (GLU) and total protein (TP). A positive relationship between
      hepatocyte vacuolization index and hepatosomatic index was found, suggesting that
      lipid accumulation could have contributed to the increase of liver weight. The
      hepatic alterations recorded included general diagnostic categories and
      additionally large areas of heterogeneous parenchyma, composed of hepatocytes
      with different spectrum of vacuolization. Liver histopathological evaluation
      revealed a sample prevalence of 34% for heterogeneous parenchyma, 31% for foci of
      necrosis and 9% for non-neoplastic lesions. No neoplastic lesions were found.
      Livers with heterogeneous parenchyma showed higher Cu and Zn content than livers
      without this category of lesion, suggesting that metals accumulated could trigger
      this hepatic alteration. AST was higher in mullets from the lagoon than in
      mullets from the sea, but no differences in ALP and ALT were found, suggesting a
      change in protein metabolism as an adaptive response to metals exposure. The
      higher glucose and protein contents observed in fish caught in the lagoon are
      consistent with a stress response and the measurement of plasma AST activity
      could be a sensitive indicator of lagoon fish stress. In conclusion, Esmoriz
      Paramos lagoon biomonitorization, using indicator species will proceed to assess
      the impact of the restoration program under development by the Portuguese
      government.

PMID- 18058034
TI  - Speciation of inorganic arsenic in coastal seawater from Ionian and Tyrrhenian
      seas (Sicily, Italy) using derivative anodic stripping chronopotentiometry.
AB  - The purpose of this paper was to use derivative anodic stripping
      chronopotentiometry (dASCP) as a sensitive and accurate technique, to determine
      the concentrations of dissolved As (III) and As (V) in coastal seawater samples
      from the Straits of Messina, the Ionian and the Tyrrhenian seas, and to
      investigate the relationship between the anthropogenic activities on the coastal
      areas and the concentration of dissolved inorganic arsenic in seawaters. The
      obtained data indicated that As (V) was the most abundant species, with
      concentration ranging from 26.7 to 307 nM, whereas As (III) levels were lower
      than 48 nM in all the samples. In particular, As (III) and As (V) levels
      significantly decreased from high to low anthropogenic activities zones (p <
      0.00001, ANOVA), with the reference samples, from a wildlife reserve, showing the
      lowest values. Furthermore it was observed that human activities influenced
      inorganic arsenic speciation, since the zones that received high human input
      presented the highest As(V)/As (III) ratio.

PMID- 18058035
TI  - Should comprehensive diagnosis include idiographic understanding?
AB  - The World Psychiatric Association has emphasised the importance of idiographic
      understanding as a distinct component of comprehensive assessment but in
      introductions to the idea it is often assimilated to the notion of narrative
      judgement. This paper aims to distinguish between supposed idiographic and
      narrative judgement. Taking the former to mean a kind of individualised
      judgement, I argue that it has no place in psychiatry in part because it
      threatens psychiatric validity. Narrative judgement, by contrast, is a genuinely
      distinct complement to criteriological diagnosis but it is, nevertheless, a
      special kind of general judgement and thus can possess validity. To argue this I
      first examine the origin of the distinction between idiographic and nomothetic in
      Windelband's 1894 rectorial address. I argue that none of three ways of
      understanding that distinction is tenable. Windelband's description of historical
      methods, as a practical example, does not articulate a genuine form of
      understanding. A metaphysical distinction between particulars and general kinds
      is guilty of subscribing to the Myth of the Given. A distinction based on an
      abstraction of essentially combined aspects of empirical judgement cannot
      underpin a distinct empirical method. Furthermore, idiographic elements
      understood as individualised judgements threaten the validity of psychiatric
      diagnosis. In the final part I briefly describe some aspects of the logic of
      narrative judgements and argue that in the call for comprehensive diagnosis,
      narrative rather than idiographic elements have an important role. Importantly,
      however, whilst directed towards individual subjects, narratives are framed in
      intrinsically general concepts and thus can aspire to validity.

PMID- 18058036
TI  - Reliability and validity of the social integration survey (SIS) in patients with
      schizophrenia.
AB  - INTRODUCTION: Schizophrenia-related impairments impact functional status and
      health-related quality of life. The Social Integration Survey (SIS) measures
      social functioning outcomes in schizophrenia from patient and informant
      perspectives. METHODS: A total of 129 patient/informant dyads at eight US sites
      participated. Patients were at least 18 years old, with schizophrenia or
      schizoaffective disorder for 1 year or more, residing in the community.
      Informants were at least 21 years old, cared for patient at least 1 month, with
      contact at least twice weekly. The SIS, PSP, PETiT, QLS, CGI-S, and PANSS were
      completed. Individual item performance, subscale development, reliability, and
      validity were examined. RESULTS: Items were easily understood and responses well
      distributed for patients and informants. Four of five subscales identified were
      internally consistent (alphas >or=0.68) and stable over time. Inter-rater
      reliability was low. SIS scores were not strongly correlated with other measures,
      except PETiT Quality of Life. The SIS differentiated on social functioning at
      varying levels of symptom severity (P < 0.05). CONCLUSIONS: Patient and informant
      completed versions showed adequate internal consistency, test-retest reliability,
      and discriminant validity. Lack of correspondence between patient and informant
      responses and construct validity require further examination. Work-related items
      were inapplicable for most patients, but would be for those with higher
      functioning.

PMID- 18058040
TI  - Common mental health problems in historically disadvantaged urban and rural
      communities in South Africa: prevalence and risk factors.
AB  - This paper reports on an epidemiological study of common mental health and
      substance abuse problems in a historically disadvantaged urban and rural
      community in South Africa. In the rural Limpopo Province of South Africa, and in
      a peri-urban township near Cape Town, self-report instruments were used in two
      random population samples and among respondents at primary care and traditional
      healer settings, to assess common mental health problems, substance abuse
      problems and associated problems in social functioning. A high prevalence of
      mental health and substance abuse problems was observed in both communities, with
      highest rates in the peri-urban township. Even higher prevalences were found
      among respondents at primary health care or traditional healers. The study shows
      that mental health and substance abuse problems constitute a considerable burden
      of disease among disadvantaged communities in South Africa. The study further
      underscores the integral role of traditional healers in the mental health care
      system.

PMID- 18058038
TI  - Hepatitis B viral factors and clinical outcomes of chronic hepatitis B.
AB  - Hepatitis B virus (HBV) infection is an important health problem and the major
      cause of chronic hepatitis, cirrhosis as well as hepatocellular carcinoma (HCC)
      worldwide. The natural history of chronic HBV infection can be divided into 4
      dynamic phases in HBV carriers who acquire the virus early in life. In general,
      the frequency and severity of hepatitis flares in the immune clearance or
      reactivation phase predict disease progression in HBV carriers, and early HBeAg
      seroconversion typically confers a favorable outcome. In contrast, late or absent
      HBeAg seroconversion after multiple hepatitis flares accelerates the progression
      of chronic hepatitis to cirrhosis. Recently, several hepatitis B viral factors
      predictive of clinical outcomes have been identified. For example, serum HBV DNA
      level at enrollment is the best predictor of adverse outcomes (cirrhosis, HCC and
      death from liver disease) in adults with chronic HBV infection. In addition, HBV
      genotype C, basal core promoter (BCP) mutant and pre-S deletion mutant are
      associated with increased risk of HCC development. In conclusion, hepatitis B
      viral factors such as serum HBV DNA level, genotype and mutants have already been
      clarified to influence disease progression of chronic hepatitis B. Further
      studies are needed to investigate the pathogenic mechanism of each viral factor.

PMID- 18058041
TI  - Survey of airborne polyfluorinated telomers in Keihan area, Japan.
AB  - Perfluorooctanoate (PFOA) are environmental contaminants posing special public
      health concerns because of their long-term persistence and bioaccumulation in the
      environment. Fluorotelomer alcohols are volatile and may undergo long-range
      transport. Air samples were collected at five sites in the Keihan area, Japan:
      Sakyo, Morinomiya and three sites in Higashiyodogawa. Except for Higashiyodogawa,
      the highest concentrations of fluorotelomer alcohols (FTOHs) were for 8:2 FTOH
      (median 447 pg m(-3)) followed by 10:2 FTOH (56 pg m(-3)) and 6:2 FTOH (22 pg m(
      3)). In contrast, 8:2 FTOAcryl (median 865 pg m(-3)) and 8:2 FTOH (1,864 pg m(
      3)) were both major components in Higashiyodogawa. Compared to data published for
      North America and Europe, 8:2 FTOH levels are significantly higher in Keihan,
      suggesting a possible point source.

PMID- 18058037
TI  - Structural genomics of protein phosphatases.
AB  - The New York SGX Research Center for Structural Genomics (NYSGXRC) of the NIGMS
      Protein Structure Initiative (PSI) has applied its high-throughput X-ray
      crystallographic structure determination platform to systematic studies of all
      human protein phosphatases and protein phosphatases from biomedically-relevant
      pathogens. To date, the NYSGXRC has determined structures of 21 distinct protein
      phosphatases: 14 from human, 2 from mouse, 2 from the pathogen Toxoplasma gondii,
      1 from Trypanosoma brucei, the parasite responsible for African sleeping
      sickness, and 2 from the principal mosquito vector of malaria in Africa,
      Anopheles gambiae. These structures provide insights into both normal and
      pathophysiologic processes, including transcriptional regulation, regulation of
      major signaling pathways, neural development, and type 1 diabetes. In conjunction
      with the contributions of other international structural genomics consortia,
      these efforts promise to provide an unprecedented database and materials
      repository for structure-guided experimental and computational discovery of
      inhibitors for all classes of protein phosphatases.

PMID- 18058042
TI  - Baseline concentrations of trace metals in macroalgae from the Strait of
      Magellan, Chile.
AB  - Samples of four different species of seaweed were collected monthly between
      October 2000 and March 2001 from the coast of the Strait of Magellan, Chile to
      establish baseline levels of trace metals (silver, total mercury, nickel, lead,
      antimony, vanadium and zinc) and to compare the accumulation capacity among
      species. The algae included in the study were Adenocystis utricularis (n=15);
      Enteromorpha sp. (n=11), Mazzaella laminarioides (n=12) and Porphyra columbina
      (n=6). The concentration range of each metal in microg g(-1) dry weight varied as
      follows: Ag=ND-0.3, Hg=ND-0.02, Ni=ND-12.6, Pb = ND-11.2, Sb=ND-1.97, V=ND-11.34
      and Zn=14.10-79. Results showed that levels of Ag, Hg, Ni, Pb, Sb, V and Zn for
      all species were similar to those found in other studies for non-contaminated
      areas with very little influence from anthropogenic activity. Also among the four
      species studied macroalgae Enteromorpha sp. had the highest capacity for metal
      accumulation and could therefore be considered as a biomonitor for future studies
      in the area.

PMID- 18058043
TI  - The metal content of bivalve molluscs of a coastal lagoon of NW Mexico.
AB  - The lagoonal system Altata-Ensenada del Pabellon supports important traditional
      fisheries and mollusc cultures and receives urban and agricultural effluents. The
      annual mean Cd contents of the oyster and mussel Crassostrea gigas and Mytella
      strigata of the inner mangrove swamps were higher than that of the clam
      Megapitaria squalida, which lives in areas under marine influence. Crassostrea
      corteziensis had the highest Cu and Zn contents, showing that it is a strong
      accumulator of both metals and especially of Zn, and there were no significant
      differences in the Pb content of the three species.

PMID- 18058044
TI  - Spectrophotometric determination of endosulfan using thionin and methylene blue
      as chromogenic reagents.
AB  - A simple, selective and sensitive spectrophotometric method is proposed for the
      determination of widely used organochlorine pesticide endosulfan using thionin
      and methylene blue as chromogenic reagents. The method is based on the liberation
      of sulfur dioxide from endosulfan by adding acid reagent and alcoholic potassium
      hydroxide. The liberated sulfur dioxide is passed through potassium iodate
      solution and the iodine so liberated bleaches the violet color of thionin and
      blue color of methylene blue and is measured at 600 nm and 665 nm respectively.
      This decrease in absorbance is directly proportional to the endosulfan
      concentration. The Beer's law is obeyed in the range of 0.4-7.0 and 0.2-9.0
      microg mL(-1) of endosulfan using thionin and methylene blue as reagents
      respectively. The molar absorptivity and Sandell's sensitivity were found to be
      1.05 x 10(5) and 5.03 x 10(4) L mol(-1) cm(-1), 3.85 x 10(-3) and 8.10 x 10(-3)
      microg cm(-2) of endosulfan using thionin and methylene blue as reagents
      respectively. The method has been applied for the determination of endosulfan in
      water, soil and vegetables.

PMID- 18058045
TI  - Concentrations and distribution of mercury and other heavy metals in surface
      sediments of the Yatsushiro Sea including Minamata Bay, Japan.
AB  - The concentrations and distribution of heavy metals, such as mercury, zinc,
      copper, lead, and iron in surface sediments from 234 stations of the Yatsushiro
      Sea including Minamata bay were investigated. High concentrations of mercury were
      found in sediments from Minamata bay and its vicinity, but the levels decreased
      gradually with distance from the bay. The concentrations of mercury in sediments
      decreased gradually from south to north of the Yatsushiro Sea. These imply the
      lack of movement of mercury from Minamata bay to the northern Yatsushiro Sea. The
      geographical profiles of zinc and copper were contrary to that found for mercury,
      indicating the presence of natural and anthropogenic sources of copper and zinc
      in the northern Yatsushiro Sea.

PMID- 18058046
TI  - Degradation dynamics and persistence of Quinolphos and Methomyl in/on Okra
      (Ablemoschus esculentus) fruits and cropped soil.
AB  - Dissipation of Quinalphos (Ekalux 20 AF) and Methomyl (Lannate 12.5 L) residues
      were studied in/on Okra (var. Pusa Sawani) fruits and cropped soil at Baruipur,
      West Bengal, India. The insecticides were applied at 21 days after sowing by
      foliar spray at the recommended and double the recommended dose (i.e. 500 and
      1,000 g a.i. ha(-1) in both the cases). Four sprays were given at 15 days
      interval in all the cases. The initial build-up residue on Okra fruits was to the
      magnitude of 3.20 and 7.50 microg g(-1) for Quinalphos, 5.61 and 8.42 microg g(
      1) for Methomyl at lower and higher doses respectively. The half-lives (t(1/2))
      in Okra fruit were found to be 1.25-1.43 days for Quinalphos and 0.88-0.94 days
      for Methomyl. The safe waiting period (T(MRL)) determined were 6.7 and 5.3 days
      at the lower dose of Quinalphos. The corresponding waiting period for Methomyl
      were 5.7 and 4.9 days. Decontamination process like washing and cooking dislodged
      25.50%-81.50% residue depending on insecticides and doses, whereas 20.00%-69.60%
      surface residue was removed by washing alone. The residues of both insecticides
      in soil persisted for 6-8 days depending on dose. The half-lives in soil were
      found to be 1.07-1.20 days for Quinalphos and 0.97-1.25 days for Methomyl.

PMID- 18058047
TI  - Effect of waterborne copper on the microstructures and ultrastructure of the X
      organ sinus gland complex in Eriocheir sinensis.
AB  - The effects of different water-borne copper (Cu(2+)) concentrations on the
      microstructures and ultrastructures of the X-Organ sinus gland (XO/SG) in
      Eriocheir sinensis were studied. Under a light microscope, no significant
      differences were found between the treated and control groups. Under Transmission
      Electron Microscopy (TEM), the mitochondrial cristae in the neuro-terminal of the
      XO of the 5.00 mg/L Cu(2+) treated group disappeared, or even only a few vacuoles
      left. No other differences were found in SG between the 0.01, 0.10, and 1.00 mg/L
      Cu(2+) treated and the control group under light microscopy, except for the 5.00
      mg/L Cu(2+) treated groups, in which the boundary between the SG hemocoels and
      glial cells became unclear, and some central hemocoels closed and even
      disintegrated. In addition, in the 5.00 mg/L Cu(2+) treated groups the hemocytes
      mixed with the glial cells, axon terminal disordered arranged, and furthermore,
      under the TEM glial cells ruptured, mitochondrial cristae disappeared, or even
      remained only a vacuoles. Such a change also occurred in the mitochondria in the
      axon terminal. In some of the glial cells the structure of the membrane
      disintegrated, the cytoplasm disappeared, and the nucleus entered the haemocoels
      being piled together with the hemocytes. The axon terminal and neurosecretory
      granular decreased near the amorphous figurationling of the haemolymph. The
      results indicate that the damage to the microstructure and ultrastructure of the
      XO/SG was relevant to the elevated water-borne copper concentration in E.
      sinensis.

PMID- 18058048
TI  - The effect of multi-generational exposure to metals and resultant change in
      median lethal toxicity tests values over subsequent generations.
AB  - A study was conducted on the long term effects of nine heavy metals on the
      Chironomus plumosus and Culicoides furens larvae. This study tested the effect of
      the heavy metals on several generations of the larvae to observe the formation of
      increased hardiness against pollutants present within the aquatic habitat. From
      this study it was observed that susceptibility or sensitivity to heavy metals
      decreased with LC50 values becoming larger indicating a decreased toxicity level.
      Significant variations (p < 0.05) were observed between first generation and
      third generation culicoides for all metals and at all concentrations. Variations
      between third and fourth generation culicoides were also significantly different
      (p < 0.05) with the exception of chromium at 25 degrees C and nickel and lead at
      every temperature range group. The variation between all generations 4, 5 and 6
      was found to be insignificant (p > 0.05). This would indicate that metal
      tolerance would have occurred in these generations and the effect of metals was
      less toxic to the culicoides. Generation 9 was found to have LC50 values (p >
      0.05) the same as the LC50 values obtained in third generation culicoides. Thus
      it would appear that heavy metal resistance was developed when the organisms were
      exposed to prolonged exposure of the heavy metals but was lost when the organisms
      were bred in non-contaminated water.

PMID- 18058049
TI  - Single strand dna breaks in human lymphocytes exposed to para-phenylenediamine
      and its derivatives.
AB  - Para-Phenylenediamine (PPD), the main aromatic amines used in the hair dye
      formation, and its four derivatives (2-chloro-p-phenylenediamine, 4-chloro-o
      phenylenediamine, 2-nitro-p-phenylenediamine, and 4-nitro-o-phenylenediamine)
      were examined for their potential to produce single strand DNA breaks in human
      lymphocytes using the alkaline comet assay. Results revealed that all the tested
      chemicals within the range of doses from 100 microM to 500 microM showed the
      genotoxicity in a dose-dependent manner after the incubation of lymphocytes with
      these chemicals for 2 h. In this study, we first reported that PPD and its four
      derivatives can elicit the type of single strand breaks in human lymphocytes.

PMID- 18058050
TI  - Autotrophic biofilm development on superficial samples of the gold-silver mine
      tailings, Valenciana (Mexico): pioneers in tailings remediation?
AB  - We report the results of long term bio-assays on microorganism colonization of
      mine tailings samples, taken from the Valenciana mine tailings (Guanajuato,
      Mexico), under stable laboratory conditions (humidity, temperature, light
      exposure). In order to identify the main metabolic groups of the potentially
      colonizing microorganisms and the implications of their growth on the main
      tailing's characteristics related to biological succession, organic matter (OM)
      content, cationic exchange capacity (CEC), and pH values were measured as the
      colonization took place. We observe that photosynthetic biofilms (cyanobacteria,
      green algae, and diatoms) successfully colonize the mine tailings samples as
      pioneers; moreover, bacteria, yeast and fungi were also identified. Biofilm
      colonization significantly improved the OM contents, whereas the pH value is not
      modified during the entire observed colonization process. The results suggest
      that biofilms are useful during the first steps of the mine tailings remediation.
      This is the first report of microalgae and cyanobacteria grown of on tailings
      samples obtained from a semiarid region.

PMID- 18058051
TI  - Acute toxicity of synthetic pyrethroid cypermethrin to some freshwater organisms.
AB  - Ninety-six hours static bioassays were made in the laboratory to determine acute
      toxicity of cypermethrin to five non-target freshwater organisms belonging to
      different taxa and niche. Susceptibility of the organisms to cypermethrin was in
      the order: the crustacean Diaptomus forbesi > the aquatic insect Ranatra
      filiformis > the freshwater carp Cyprinus carpio > the tadpole larva of the toad
      Bufo melanostictus > the oligochaet worm Branchiura sowerbyi. Ninety-six hours
      LC50 values of aqueous cypermethrin ranged from 0.03 microg/L for the crustacean
      to 9.0 microg/L for the tadpole larva. The value was very high (71.12 microg/L)
      for the oligochaet worm. LC50 values changed with hours of exposure till 72 h
      after which cypermethrin became inactive in both aqueous and acetone solution.
      Acetone solution of cypermethrin was more toxic to B. sowerbyi, C. carpio and the
      tadpole larva. There was no significant difference in susceptibility of any other
      test organism between aqueous and acetone solution of cypermethrin.

PMID- 18058052
TI  - Decolorization of cotton pulp black liquor by pleurotus ostreatus in a bubble
      column reactor.
AB  - Decolorization of cotton pulp black liquor by Pleurotus ostreatus B1 in a bubble
      column reactor (BCR) was studied. The optimal conditions for the running of BCR
      are 30 degrees C, pH 6.0, aeration rate 1.2 L min(-1), and mycelial age 7 days.
      Under the optimal conditions, the BCR was run for four cycles (each cycle, 12
      days) and the same mycelial pellets were reused. The ultimate decolorization and
      COD removal rates are 76% and 80%, respectively.

PMID- 18058053
TI  - The association between cysteine, bone turnover, and low bone mass.
AB  - BACKGROUND: With the identification of hyperhomocysteinemia as a risk factor for
      developing osteoporosis, the contribution of thiols metabolically linked with
      homocysteine (tHcy) may be of importance. Cysteine (Cys) is formed from tHcy and
      is involved in bone metabolism via incorporation into collagen and cysteine
      protease enzymes. METHODS: We investigated the association of plasma Cys and
      related thiols, the bone turnover markers C-telopeptide (CTX) and procollagen
      type 1 N propeptide (P1NP) and folate and vitamin B(6) with calcaneal bone
      mineral density (BMD) in 328 postmenopausal British women grouped according to
      their BMD measurement. RESULTS: Subjects with low BMD had a significantly lower
      plasma Cys concentration (146.3 vs. 177.7 micromol/l, p < 0.0001), a
      significantly higher recent fracture rate (30.9% vs. 16.4%, p = 0.017), and a
      significantly higher percentage of current smokers (26.4% vs. 7.3%. p = 0.003)
      than those with normal BMD. Additionally, they had a significantly lower plasma
      Cys, and higher plasma tHcy and CTX, than those with osteopenia. In the whole
      population, Cys was significantly associated with BMD, weight, height, smoking
      habit, log creatinine, Cys-Gly, log tHcy, and log folate, but the significant
      positive association of Cys with BMD was maintained after correction for all
      other variables (r = 0.197, p = 0.003). After weight, Cys was the next most
      significant predictor of BMD in a stepwise multiple linear regression model.
      CONCLUSION: Our study suggests a significant association between plasma Cys and
      BMD. A reduced Cys concentration, possibly modulated by smoking, or reduced flux
      from tHcy, may lead to reduced availability for collagen formation. Increased
      osteoclast activation, possibly as a result of relative hyperhomocysteinemia, may
      lead to increased Cys utilization in cysteine proteases.

PMID- 18058054
TI  - Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5)
      gene are associated with peak bone mass in non-sedentary men: results from the
      Odense androgen study.
AB  - PURPOSE: To investigate the impact of the Ala1330Val (rs3736228, exon 18) and
      Val667Met (rs4988321, exon 9) polymorphisms of the low-density lipoprotein
      receptor-related protein 5 (LRP5) gene on peak bone mass in young men. METHODS:
      The Odense Androgen Study (OAS) is a population-based study comprising 783
      Caucasian men aged 20-30 years. Genotyping was performed using real-time
      polymerase chain reaction (PCR) or fluorescence polarization. Bone mineral
      density (BMD) measurements were performed using dual-energy X-ray absorptiometry.
      RESULTS: The CC, CT, and TT genotypes in Ala1330Val were found in 75.6%, 21.8%,
      and 2.6% of the participants, respectively. Similarly, the GG, GA, and AA
      genotypes of Val667Met were found in 89.7%, 9.8%, and 0.5%, respectively. For the
      Ala1330Val polymorphism, no significant differences between the genotypes were
      found regarding BMD in the overall study population. However, when analysis was
      restricted to non-sedentary men (n = 589), a significant association between the
      number of T-alleles and BMD in the spine and whole body were found. Each copy of
      the T-allele changed the Z-score of the spine by (median and 95% confidence
      interval) -0.21 [95% CI: -0.40; -0.03] (p < 0.02). Analysis suggested an
      association between the AA genotype in the Val667Met polymorphism and increased
      body height and decreased BMD of the femoral neck; however, no significant gene
      dose effect of the A-allele could be demonstrated in the whole population. When
      the analysis was restricted to non-sedentary subjects, however, each number of A
      alleles was associated with a change in Z-score of -0.26 [95% CI: -0.51; -0.01]
      (p = 0.04). No further significant results emerged with haplotype analysis.
      CONCLUSION: The Ala1330Val and Val667Met polymorphisms in the LRP5 gene are
      significantly associated with peak bone mass in physically active men.

PMID- 18058055
TI  - Wrist fracture as a predictor of future fractures in younger versus older
      postmenopausal women: results from the National Osteoporosis Risk Assessment
      (NORA).
AB  - The short-term association between wrist-fracture history and future fracture has
      not been simultaneously compared between younger and older postmenopausal women.
      This 3-year follow-up study of 158,940 women showed a similar future fracture
      risk in younger and older women with wrist-fracture history. INTRODUCTION: We
      examined the association between prior wrist fracture and future osteoporosis
      related fractures within 3 years in younger and older postmenopausal women.
      METHODS: In the National Osteoporosis Risk Assessment (NORA) study, 158,940
      postmenopausal women, aged 50-98 (median 63) years, provided information on
      fracture history since age 45, and responded to follow-up surveys 1 or 3 years
      later when new fractures were queried. Cox regression models were used to obtain
      relative risk (RR) and 95% confidence interval (CI) estimates. RESULTS: Of the
      158,940 participants, 8,665 reported a history of wrist fracture at baseline;
      4,316 women reported at least one new fracture within three years. The RR for any
      subsequent clinical fracture, adjusted for covariates and baseline BMD T-score,
      was 2.4 (2.0, 2.9) for younger and 2.1 (1.9, 2.3) for older women. A prior wrist
      fracture increased the risk of a future wrist fracture about 3-fold and doubled
      the risk of any osteoporotic fracture. CONCLUSIONS: Prior wrist fracture strongly
      predicts three-year risk of any future osteoporotic fracture for older and
      younger postmenopausal women, independent of baseline BMD and common osteoporosis
      risk factors. More consideration should be given to evaluating and managing
      osteoporosis in younger and older women with a history of wrist fracture,
      independent of their BMD.

PMID- 18058056
TI  - A study of multi-detector row CT scan on greater omentum in 50 individuals:
      correlating with anatomical basis and clinical application.
AB  - BACKGROUND: In view of the descriptions of the CT manifestations on the greater
      omentum (GO) were not precise and detailed enough in the previous literature, we
      tried to evaluate the radiologic-anatomical features of the GO and to address the
      related clinical implications for the radiologic diagnosis and surgical
      application. METHODS: We evaluated the GO by using multi-detector row CT (MDCT)
      scanning in 50 individuals correlating with anatomical basis and clinical
      application. Emphasis was placed on the following items: the anatomical
      distribution and location of the GO; the CT manifestations of the vasculature,
      fatty tissue and lymph nodes. RESULTS: The gastro-epiploic vessel, the landmark
      for delineating the GO, was visualized in 50/50 cases (100%). The gastro-colic
      vein was detected in 34/50 cases (68%). The free-hanging portion, 48 cases
      revealed, seemed to have the capability of 'migration': it is located in the
      subphrenic spaces in 9/48 cases (19%) and distributed in the right lower quadrant
      predominantly in 10/48 cases (21%). Three-dimensional reformatted images,
      obtained in five cases, demonstrated the return of the gastro-epiploic vein
      distinctly. Lymph nodes were rarely detected within the GO. CONCLUSION: The
      depicted omental vessels, visualized by using multi-planar reconstruction images
      together with three-dimensional reformatted images, played a crucial role in
      delineating the GO comprehensively. It can provide the valuable data for the
      radiologic diagnosis and surgical therapy planning including surgery of
      reconstruction, pancreas, portal hypertension as well as infections and
      neoplastic diseases.

PMID- 18058057
TI  - The phrenico-esophageal ligament: an anatomical study.
AB  - The phrenico-esophageal ligament (PEL), which is claimed by some to be an
      important anti-reflux barrier, has been accepted as an important structure by
      some surgeons dealing with the surgical treatment of hiatal hernias. However, the
      characteristics of its anatomical structure and the physiological importance of
      this ligament is still a subject of discussion. The aim of this study was to
      define this anatomic structure and to point out the clinical importance of the
      PEL. This study has been carried out on samples taken from 2 fresh and 12 fixed
      cadavers. The PEL was observed to be derived from the transversalis and
      endothoracic fascia attaching the esophagus to the diaphragmatic crura at the
      region of the esophageal hiatus. While the transversalis fascia covered the
      inferior surface of the diaphragm, it was observed to divide into upper and lower
      leaflets when it approached the esophageal hiatus. The endothoracic fascia turned
      superiorly at the level of esophageal hiatus and attached on to the esophagus by
      uniting with the upper leaflet of the transversalis fascia in 11 of the
      specimens. In three of the specimens, it attached on the esophagus at a higher
      level than the transversalis fascia. The histologic sections of our study
      revealed that the PEL is formed by collagen and elastic fibers composed of
      fibroblasts and blood vessels. Since the PEL is a strong structure that firmly
      attached to the esophageal wall and surrounded the upper part of the distal
      esophagus like a skirt, it is reasonable that it may play an important role in
      the gastroesophageal sphincteric mechanism. Histological evidence for decrease in
      collagen fibers with age and the loose arrangement of the elastic fibers due to
      this decrement might decrease the resistance and the elasticity of the PEL. This
      situation may explain the predisposition to hiatal hernias seen with increased in
      age.

PMID- 18058058
TI  - Side selection of pterional approach for anterior communicating artery aneurysms-
      surgical anatomy and strategy.
AB  - BACKGROUND: To evaluate our decision policy based on vertical aneurysm projection
      for selecting the side of the pterional approach for the surgical treatment of
      anterior communicating artery aneurysms. METHODS: Inferiorly projecting aneurysms
      were treated through the dominant A1 side, and superiorly projecting aneurysms
      were treated through the side of aneurysm fundus projection. We analysed
      postoperative outcome and surgical complications, and the correlations between
      the anatomical factors such as position (high or low), projection (dorsal or
      anterior), and the plane containing both A2 vessels (open A2 plane defined as the
      A2 of the approach side located more posteriorly than the contralateral A2;
      closed A2 plane as the ipsilateral A2 located more anteriorly than the
      contralateral A2), to assess the surgical requirements of approaches in patients
      with superiorly projecting aneurysms. FINDINGS: A favorable outcome was achieved
      in 95.1% of patients with inferior type aneurysms and 85.2% of patients with
      superior type aneurysms (P = 0.088). Surgical complications occurred in 8.9% of
      patients with inferior type aneurysms and 17.9% with superior type aneurysms.
      However, there was a distinct group of patients with superior type aneurysms
      characterised by a closed A2 plane, in which the ipsilateral A2 was located
      anterior to the contralateral A2, in whom the approach toward the neck was
      significantly more difficult, requiring A2 displacement or gyrus aspiration, and
      resulting in a neck remnant and more surgical complications such as vascular
      injury or cerebral contusion. This group also had a significantly high
      correlation with high position and dorsal projection of aneurysms causing more
      difficult dissection. CONCLUSIONS: This policy provided good postoperative
      outcomes. However, use of skull base techniques or the interhemispheric approach,
      instead of the normal pterional approach, may further improve the postoperative
      outcome for closed A2 plane aneurysms.

PMID- 18058059
TI  - Spontaneous resolution of isolated dissecting aneurysm on the posterior inferior
      cerebellar artery.
AB  - The authors report a rare example of an isolated dissecting posterior inferior
      cerebellar artery (PICA) aneurysm with spontaneous resolution. A 41 year-old male
      suffered sudden dizziness, nausea and vomiting. An angiogram and magnetic
      resonance imaging (MRI) detected an isolated PICA dissection. The patient was
      treated conservatively and recovered without any apparent neurological deficit.
      MRI detected the self-resolution of the dissecting aneurysm. Dissecting PICA
      aneurysms, especially non-haemorrhagic lesions, have the possibility of
      spontaneous resolution resulting in a favorable outcome. The treatment strategy
      for this vascular lesion may be decided based upon neuroradiological changes on
      careful follow-up.

PMID- 18058060
TI  - Cordectomy for post-traumatic syringomyelia.
AB  - We performed cordectomy, a surgical technique that is infrequently used at
      present, for a patient with post-traumatic syringomyelia (following complete
      paraplegia of both lower limbs due to dislocation fracture of the 9th thoracic
      vertebra), yielding a favourable result. We recommend cordectomy as a surgical
      technique to which spinal surgeons should give utmost consideration for patients
      with post-traumatic syringomyelia demonstrating progressive symptoms assumed to
      be attributable to the syrinx and with an anatomically transected spinal cord of
      the mid-to-lower thoracic vertebral level.

PMID- 18058061
TI  - Ependymoma of conus medullaris presenting as subarachnoid haemorrhage.
AB  - Subarachnoid haemorrhage (SAH) due to spinal ependymoma is very rare. We report a
      37 year old man who presented with typical clinical signs of SAH. Lumbar puncture
      confirmed SAH but cerebral angiography was negative, and further diagnostic work
      up revealed an ependymoma of the conus medullaris as the source of the
      haemorrhage. A comprehensive review of the literature was conducted. Only 17
      patients with spontaneous SAH due to a spinal ependymoma have been reported since
      1958. However, in cases of SAH and negative diagnostic findings for cerebral
      aneurysms or malformations, this aetiology should be considered and work-up of
      the spinal axis completed.

PMID- 18058062
TI  - Validation of the Edinburgh Postnatal Depression Scale in an Iranian sample.
AB  - BACKGROUND: Considering the adverse effects of postpartum depression on both
      mother and infant, a screening instrument for early diagnosis seems to be of
      importance. AIMS: To assess the psychometric properties of the Persian version of
      Edinburgh Postnatal Depression Scale (EPDS) on a sample of Iranian postpartum
      women. METHOD: The EPDS was translated and back-translated in the standard
      method. The questionnaire was completed by 600 postpartum women. Hundred cases
      with an EPDS score of > or =9 and 100 cases with an EPDS of <9 were randomly
      selected for interview. Sensitivity, specificity, positive likelihood ratio, and
      receiver operating characteristics were calculated by comparing the EPDS sum
      score against the DSM-IV diagnoses. The correlation coefficient of the EPDS score
      with GHQ-12 score was calculated. Principal component analysis and internal
      consistency were assessed. RESULTS: The best cutoff scores for major depression
      were 12/13 with a sensitivity and specificity of 95.3% and 87.9%, respectively.
      The correlation coefficient of the total score of the Persian version of EPDS
      with the GHQ-12 total score was 0.76 (P < 0.001). A two-factor solution was
      selected as the most appropriate model based on both values and the score plot.
      The coefficient alpha for the whole scale was 0.83. CONCLUSION: The Persian
      version of EPDS is a reliable and valid measure for detecting postpartum
      depression. Furthermore, it seems acceptable to patients and a valid screening
      instrument for depression in postpartum women.

PMID- 18058063
TI  - The role of the N-terminal caspase cleavage site in the nucleoprotein of
      influenza A virus in vitro and in vivo.
AB  - The N-terminal caspase cleavage in the nucleoprotein (NP) of influenza A virus is
      correlated with the host origin of the virus, thus could be a molecular
      determinant for host range. We studied how mutations targeting the NP cleavage
      motif of human and avian influenza viruses affect virus replication in vitro and
      in vivo. The "avian-like" D16-->G substitution in the NP, which makes this
      protein resistant to cleavage, did not significantly affect the human A/Puerto
      Rico/8/34 (H1N1) virus replication in vitro but decreased the lethality of this
      virus in mice by 68-fold. Gene incompatibility contributed to the attenuated
      phenotype of the reassortant A/Puerto Rico/8/34 virus with avian NP derived from
      A/Teal/Hong Kong/w312/97 (H6N1) virus in vitro and in vivo. Insertion of the
      "human-like" G16-->D mutation into avian NP, which resulted in susceptibility to
      caspase cleavage, did not rescue virulence, but made the reassortant virus even
      more attenuated. Introducing the human-like G16-->D substitution into the NP of
      highly pathogenic A/Vietnam/1203/04 (H5N1) virus decreased lethality in mice. We
      confirmed that position 16, which associated with the N-terminal caspase cleavage
      of the NP, is important for optimal virus fitness in vitro and in vivo. An avian
      like mutation at position 16 in the NP of human virus as well as a human-like
      substitution at this residue in avian NP both resulted in virus attenuation.

PMID- 18058064
TI  - Identification of a significant association of a single nucleotide polymorphism
      in TNXB with systemic lupus erythematosus in a Japanese population.
AB  - Systemic lupus erythematosus (SLE) is one of the common autoimmune diseases, with
      complex genetic components. Here, we report on a case-control association study
      of 178 SLE patients and 899 control subjects, using genome-wide gene-based single
      nucleotide polymorphism (SNP) markers. An SNP, rs3130342, in a 5' flanking region
      of the TNXB gene revealed a significant association with SLE [P = 0.000000930,
      odds ratio (OR) 3.11, with 95% confidence interval (95%CI) of 1.89-5.28] in a
      Japanese population. This association was replicated independently with 203 cases
      and 294 controls (P = 0.0440, OR 1.52, with 95%CI of 1.01-2.78). Although a copy
      number variation (CNV) of the C4 gene adjacent to the TNXB gene was reported to
      be associated with SLE, our analysis on this CNV revealed that the association of
      CNV of the C4 gene was weaker than the SNP in the TNXB gene and likely to reflect
      the linkage disequilibrium between C4 CNV and this particular SNP. Stratified
      analysis also revealed that the association of SNP rs3130342 with SLE was
      independent of the HLA-DRB1*1501 allele that has been shown to be associated with
      SLE. Our findings strongly imply that the TNXB gene is a candidate gene
      susceptible to SLE in the Japanese population.

PMID- 18058065
TI  - The role of transperineal ultrasonography in the assessment of the internal
      opening of cryptogenic anal fistula.
AB  - PURPOSE: The aim of this study was to assess the reliability of transperineal
      ultrasonography (TPUS) in the pre-operative identification of the internal
      opening of anal fistulas compared to conventional proctological examination and
      operative findings. METHODS: Forty-three patients with anal fistula were assessed
      by TPUS with and without the use of hydrogen-peroxide injection (E-TPUS) in an
      attempt to identify the internal opening. Results were compared to preoperative
      conventional examination and operative findings. RESULTS: Operative assessment
      showed an anterior internal opening in 29 patients (67.4%) and a posterior
      opening in 14 (32.6%). Compared to the operative findings, the agreement rate for
      the identification of the internal opening was 74.4% for physical examination
      alone, 93.0% for TPUS and 90.7% for E-TPUS. Physical examination was less
      accurate in detecting the internal opening than both TPUS (p=0.014) and E-TPUS
      (p=0.026). CONCLUSIONS: TPUS and E-TPUS are superior to physical examination in
      the identification of internal openings in anal fistulas. Hydrogen peroxide
      injection does not provide additional advantages.

PMID- 18058066
TI  - Comparative evaluation of the effect of sustained inflation and rapid
      inflation/deflation of the intrarectal balloon upon rectoanal inhibitory reflex
      parameters in asymptomatic subjects.
AB  - PURPOSE: The effects of rapid sustained inflation versus rapid
      inflation/deflation of the intrarectal balloon upon rectoanal inhibitory reflex
      (RAIR) parameters were evaluated in asymptomatic subjects. METHODS: Forty
      asymptomatic adults were submitted to anorectal manometry with rapid or sustained
      inflation with 30 and 60 mL air. The average age was 27.4 years (range, 20-40).
      The subjects were divided into Group I (20 men) and Group II (20 women) for
      analysis. RAIR parameters were registered in order to compare the inflation
      patterns within each group, and Groups I and II were compared for each inflation
      pattern with regard to RAIR parameters. RESULTS: Sustained inflation
      significantly increased IAS relaxation time and duration of the reflex in both
      groups, and IAS tone recovery time in Group I. CONCLUSIONS: RAIR parameters are
      influenced by the choice of inflation pattern. Further studies are required to
      establish a standard intrarectal balloon inflation pattern.

PMID- 18058067
TI  - Genetics of migraine and pharmacogenomics: some considerations.
AB  - Migraine is a complex disorder caused by a combination of genetic and
      environmental factors. Although family and twin studies show that there is a
      genetic component in migraine, no genes predisposing to common forms of the
      disorder, migraine with and without aura, have been identified. Patients with
      migraine respond differently to a given drug administered. The efficacy of
      therapy and the occurrence of adverse drug response are a consequence of
      individual variability. Genetic profiling of predisposition to migraine should
      facilitate the development of more effective diagnostic and therapeutic
      applications. The development of International Hap Map project could provide a
      powerful tool for identification of the candidate genes in this complex disease
      and pharmacogenomics research could be the promise for individualized treatments
      and prevention of adverse drug response.

PMID- 18058068
TI  - Epstein-Barr virus-associated T/NK cell-type central nervous system lymphoma
      which manifested as a post-transplantation lymphoproliferative disorder in a
      renal transplant recipient.
AB  - A 31-year-old male, who had received a cadaveric renal allograft in April 2003,
      consulted a clinic for a transient hemiplegia in August 2004. At that time, a
      course observation without medication was chosen. In October 2004, he was
      admitted to our hospital by ambulance with a clonic seizure and a recurrence of
      hemiplegia on the right side of his body. Head magnetic resonance imaging (MRI)
      showed enhanced multifocal nodular lesions with remarkable cerebral edema mainly
      in the left frontal lobe. A stereotactic brain biopsy was performed, and the
      pathological diagnosis was nasal type extranodal T/NK cell lymphoma manifested as
      the post transplant lymphoproliferative disease (PTLD). Systemic staging workups
      showed no extra-CNS involvement. Because of his renal dysfunction and no sign of
      any extra-CNS involvement, a reduction of the immunosuppressants and whole brain
      radiation therapy (WBRT) (40 Gy) without chemotherapy were applied to his
      therapeutic regimen. After WBRT, MRI showed a remarkable reduction in the number
      and size of the tumors, and no neurological abnormalities were physically
      observed. As of December 2006, no sign of recurrence has subsequently been found
      in both the intra- and extra-CNS.

PMID- 18058070
TI  - In vivo functions of the gamma-butyrolactone autoregulator receptor in
      Streptomyces ambofaciens producing spiramycin.
AB  - A gene encoding a gamma-butyrolactone autoregulator receptor was cloned in to E.
      coli from Streptomyces ambofaciens producing spiramycin, a macrolide antibiotic
      used in both veterinary medicine and human medicine. A 714-bp intact receptor
      gene (saaR) was obtained by PCR and genomic Southern hybridization with the 100
      bp PCR product as a probe. To clarify the in vivo function of saaR, a saaR
      disrupted strain was constructed by means of homologous recombination, and
      phenotypes were compared with those of the wild-type strain. The number of saaR
      disruptant spores was 4-fold less than that of the wild-type strain. In addition,
      saaR deletion from the S. ambofaciens chromosome resulted in complete loss of
      spiramycin production suggesting that saaR is a rare positive regulator,
      controlling both spiramycin biosynthesis and sporulation.

PMID- 18058069
TI  - Vincristine and lomustine induce apoptosis and p21(WAF1) up-regulation in
      medulloblastoma and normal human epithelial and fibroblast cells.
AB  - Medulloblastomas arise in the cerebellum and are the most common pediatric
      primary malignant brain tumors. Currently, medulloblastoma patients are best
      treated with surgical removal of the tumor, adjuvant radiation therapy and
      chemotherapy. The chemotherapeutic agents that showed efficiency against
      medulloblastomas include lomustine and vincristine. However, the effects of these
      drugs on medulloblastomas as well as on other cell types is still not well
      defined. In the present report we present evidence that the cytotoxic effect of
      these drugs is not specific for medulloblastoma cells but includes also normal
      fibroblast and epithelial cells. We have also shown that vincristine and
      lomustine trigger apoptosis in all these cells through the mitochondrial pathway
      via decrease in the level of the anti-apoptosis proteins Bcl-2 and Bcl-xl,
      respectively. Intriguingly, the proportion of apoptotic cells induced in
      medulloblastoma and normal epithelial and fibroblastic cells was similar. In
      addition, vincristine induced low proportion of necrosis in medulloblastoma and
      normal fibroblast cells. Interestingly, while vincristine induced cell cycle
      delay in G2/M phase in normal as well as medulloblastoma cells, lomustine effect
      on the cell cycle was specific for medulloblastoma cells. Furthermore, we have
      shown that vincristine and lomustine up-regulated p21 protein level in a p53
      independent manner. These results shed more light on the biological effects of
      vincristine and lomustine and show that lomustine is a more specific and potent
      anti-medulloblastoma agent.

PMID- 18058071
TI  - Expression, purification and characterization of a high potential iron-sulfur
      protein from Acidithiobacillus ferrooxidans.
AB  - The high potential iron-sulfur protein (HiPIP) is involved in the iron
      respiratory electron transport chain of Acidithiobacillus ferrooxidans but its
      exact role is unclear. The gene of HiPIP from A. ferrooxidans ATCC 23270 was
      cloned and expressed in Escherichia coli, and the protein then purified by one
      step affinity chromatography to homogeneity. The molecular mass of the HiPIP
      monomer was 7250.43 Da by MALDI-TOF MS, indicating the presence of the
      [Fe(4)S(4)] cluster. The optical and EPR spectra results of the recombinant
      protein confirmed that the iron-sulfur cluster was correctly inserted into the
      active site of the protein. Site-directed mutagenesis results revealed that
      Cys25, Cys28, Cys37 and Cys50 were involved in ligating to the iron-sulfur
      cluster.

PMID- 18058072
TI  - Impact of a physician education and patient awareness campaign on the diagnosis
      and management of primary immunodeficiencies.

PMID- 18058073
TI  - Photic regulation of map kinase phosphatases MKP1/2 and MKP3 in the hamster
      suprachiasmatic nuclei.
AB  - MAP kinases (MAPKs) play a key role in photic entrainment signaling in the
      suprachiasmatic nuclei (SCN), the mammalian circadian clock. The control of MAPKs
      is a fine balance between specific kinases (MEKs) and phosphatases (MKPs), whose
      orchestration in the SCN is still unresolved. We have found MKP1/2 and MKP3
      immunoreactive-cells in the hamster SCN, whose levels are rapidly increased in
      response to transient light stimulation in the subjective night (CT 18), when
      light is able to entrain the clock. Moreover, the expression level of MKP3 varies
      under light-dark cycles and constant darkness, peaking at noon, when MAPKs are in
      their activated state and begin their inactivation. These results show a
      different perspective on MAPKs in the SCN, which includes its regulation by a
      complex net of phosphatases.

PMID- 18058074
TI  - The cytoskeleton in oligodendrocytes. Microtubule dynamics in health and disease.
AB  - Oligodendrocytes have a complex cytoarchitecture and are characterized by an
      elaborate network of microtubules. They provide the tracks for organelle
      trafficking and the intracellular translocation of myelin-specific gene products.
      The integrity of the cytoskeleton is an essential determinant of the function and
      survival of oligodendrocytes. Microtubule growth and stability are regulated by
      microtubule-associated proteins. Oligodendrocytes contain a number of microtubule
      associated proteins, including the tau proteins, which are developmentally
      regulated and especially prominent in the branching points of the cellular
      processes. Process outgrowth is regulated by the interaction of Fyn kinase with
      the cytoskeleton and by microtubule-severing proteins, such as stathmin.
      Alterations or disruption of the cytoskeleton and abundant abnormal aggregates of
      cytoskeletal proteins often accompany neurodegenerative diseases, and inclusion
      bodies, resembling protein aggregates found in neurons, are prominent in
      oligodendroglial lesions in white matter pathology. This review emphasizes the
      role of the cytoskeleton, particularly of microtubules and their associated
      proteins, in oligodendrocytes during developmental processes. Furthermore, recent
      data on protein aggregate formation in oligodendroglial cells, which might occur
      during aging and disease processes, are summarized.

PMID- 18058075
TI  - Maintenance for acute myeloid leukemia revisited.
AB  - Maintenance treatment for AML is an approach to minimize residual disease,
      optimize quality of remission and prevent a leukemic regrowth over a longer
      period of time. This intention implies a certain antileukemic activity and
      myelotoxicity. Thus, a prolonged myelosuppressive maintenance is best exemplified
      by the optimized protocol of the CALGB published by Kanti R. Rai in 1981 (Blood
      58:1203-1212, 1981) and derived by the AMLCG as a therapeutic standard. From our
      today's knowledge about the impact of various strategies, a lack of postremission
      therapy is not compatible with durable remissions. Even after an induction-type
      consolidation, the classic CALGB-type maintenance, or a comparably intensive
      regimen improved the relapse-free survival over that from alternatives. Some
      studies which failed to show a benefit used maintenance at low-dosage or short
      duration. Data about maintenance delivery in patients reaching long-term
      remissions demonstrate feasibility and compliance, and a low maintenance-related
      death rate can compete with that from alternative options. Revisiting
      maintenance, however, requires a comparison with other strategies on the basis of
      intention-to-treat. Either single prospective trials or crosstrial networking by
      a common standard arm and general upfront randomization can further assess the
      relative value of maintenance for AML.

PMID- 18058076
TI  - Prediction of successful outcome in patients with primary aldosteronism.
AB  - Primary aldosteronism is one of the most common causes of secondary hypertension.
      In recent years the prevalence has risen dramatically, from 1% to 14% of all
      hypertensive patients. This has been largely attributed to an increase in
      diagnosis. Primary aldosteronism is characterized by hypertension with or without
      hypokalemia and a high plasma aldosterone concentration (PAC) with a concurrent
      low plasma renin activity (PRA). The most common subtypes of primary
      aldosteronism are aldosterone-producing adenoma (42%) and bilateral idiopathic
      hyperaldosteronism (58%). Other less common subtypes (<1%) are glucocorticoid
      remediable aldosteronism, and unilateral primary hyperplasia. Current treatment
      for primary aldosteronism relies on accurate subtype distinction and assessment
      of unilateral versus bilateral disease. Bilateral idiopathic hyperaldosteronism
      is best managed pharmacologically and improves with the use of aldosterone
      receptor antagonists. Combined treatment with sodium-channel blockers and calcium
      channel blockers has also shown satisfactory results. Glucocorticoid-remediable
      aldosteronism responds well to treatment with low-dose glucocorticoids.
      Aldosterone producing adenoma and unilateral adrenal hyperplasia are
      appropriately treated with laparoscopic adrenalectomy. Following adrenalectomy
      blood pressure improves in 98% of these patients, but only about 33% require no
      further antihypertensive medication. Identifying the subgroups that will most
      benefit from adrenalectomy is paramount to formulating individual treatment
      strategies. In the past, treatment focused mainly on the correction of
      hypertension and electrolyte disturbances. Now, with accumulating evidence of the
      detrimental effects of aldosterone to the myocardium, vascular endothelium and
      kidneys, treatment also focuses on normalizing aldosterone levels or blocking
      aldosterone action at the receptor level. Therefore, it is essential to
      accurately identify the specific subtype of primary aldosteronism in order to
      select optimal treatment and to achieve successful patient outcomes.

PMID- 18058077
TI  - [Surgery of mediastinal tumors].
AB  - Thymomas, lymphomas, and germ cell tumors are the most frequent lesions of the
      anterior mediastinum, whereas endodermal (bronchogenic) cysts and lymphomas are
      the most frequent lesions of the middle mediastinum. In the posterior
      mediastinum, neurogenic tumors and soft-tissue sarcomas are the most frequent.
      Depending on tumor location, mediastinoscopy, mediastinotomy, and thoracoscopy
      are the preferred diagnostic methods. Surgical treatment of thymoma is the gold
      standard, and median sternotomy is the most frequently applied approach. The
      decisive prognostic and therapeutic criteria are Masaoka staging, WHO
      classification, and R0 status. Thoracoscopy should be performed only in patients
      with myasthenia gravis and with very small tumors. Surgical treatment is highly
      recommended in patients with locally recurrent tumors. The importance of surgical
      treatment of germ cell tumors is determined by a negative concentration of beta
      HCG and alpha-fetoprotein and in cases of residual tumor after chemotherapy.
      Bronchogenic cysts always require resection because of their high complication
      rate (66%) after conservative treatment. In these cases complete resection is
      necessary due to the probability of recurrence. Ninety-eight percent of
      neurogenic tumors in adults are benign and usually resected via thoracoscopy or
      thoracotomy, depending on location and size.

PMID- 18058079
TI  - Canopy compass in nocturnal homing of the subsocial shield bug, Parastrachia
      japonensis (Heteroptera: Parastrachiidae).
AB  - In contrast to an open environment where a specific celestial cue is
      predominantly used, visual contrast of canopies against the sky through the gap,
      known as canopy cues, is known to play a major role for visually guided insect
      navigators in woodland habitats. In this paper, we investigated whether a
      subsocial shield bug, Parastrachia japonensis, could gauge direction using canopy
      cues on a moonless night. The results show that they could perform the round trip
      foraging behaviour even in an experimental arena with only an artificial round
      gap opened in the ceiling of the arena and adjust their homing direction for a
      new azimuth when the gap was rotated. Thus, P. japonensis can use slightly
      brighter canopy cues as a compass reference but not complex landmarks during
      nocturnal homing behaviour.

PMID- 18058078
TI  - [Relevance of cell culture models in cutaneous tumour biology. Part I: tumour
      cell lines].
AB  - Cutaneous squamous cell carcinoma, basal cell carcinoma and melanoma, much like
      all other human solid tumors, result from a multi-step process in which genetic
      and epigenetic changes accumulate in the affected cells. Insight into the biology
      of human tumors is a requirement for developing effective therapies. Cell culture
      models are a very valuable experimental system. The degree of tumorigenic
      transformation can be precisely defined. Tumor cell lines display similar
      functional hierarchy as tumors or tissues in vivo and can, consequently, provide
      a crucial source of minor cell subsets, like tumor stem cells. Progression series
      of clonally related cell lines offer the opportunity to follow the process of
      sequential acquisition of transformation-related traits up to the development of
      properties with direct clinical equivalents, like tumorigenicity and metastatic
      competence. These phenotypical changes can be directly correlated with changes at
      the genome level, concerning both gene structure and expression. While for most
      studies, human transformed cell lines are the model of choice, there are
      questions for which animal cell lines are strongly preferred, such as
      interactions between the tumor and the immune system. To properly interpret the
      results of all experiments with classical two-dimensional cell culture, a
      possible danger of artifacts due to grossly unnatural environment must be
      constantly taken into account. It is thus obligatory to confirm any such result
      with other experimental models like complex three-dimensional culture models or
      experimental animals, and with clinical samples.

PMID- 18058080
TI  - [Isolated neuritis of the oculomotor nerve in infectious mononucleosis].
AB  - A 19-year-old immune-competent patient developed right-sided headache and,
      subsequently, subacute diplopia. On clinical examination he had incomplete right
      oculomotor palsy. Cranial MRI showed pathologic contrast enhancement of the right
      oculomotor nerve at its exit point from the mesencephalon, and the CSF displayed
      slight pleocytosis. The following relevant differential diagnoses were not
      supported by additional examinations: neurosarcoidosis, Lyme neuroborreliosis,
      neurosyphilis, tuberculous meningitis, viral meningitis (HIV, VZV, CMV), CNS
      lymphoma, vasculitis associated with rheumatic disease, Tolosa-Hunt syndrome, and
      diabetic neuropathy. However, on the basis of blood lymphocytosis, positive
      heterophile antibody test (Paul-Bunnell test), the presence of IgM antibodies
      against Epstein-Barr virus capsid antigen, and elevated transaminases, infectious
      mononucleosis was diagnosed. Isolated neuritis of the oculomotor nerve is a rare
      parainfectious manifestation of infectious mononucleosis.

PMID- 18058081
TI  - [Eugen Bleuler (1857-1939) and German psychiatry].
AB  - Eugen Bleuler was born 150 years ago, and about 100 years ago he published his
      "Schizophrenia" for the very first time-giving rise to a retrospective view
      especially concerning German psychiatry. Together with Emil Kraepelin, who was
      more or less of the same epoch as Freud, E. Bleuler is one of the fathers of
      modern psychiatry. From the broad spectrum of his psychiatry with many findings,
      two achievements are particularly meaningful: the schizophrenia monography of
      1911 and the first edition of his educational manual from 1916. Psychiatry owes
      two achievements to E. Bleuler: "deepened" psychopathology, which depicted
      schizophrenic symptoms and their relation, and the importance of psychoanalysis
      for psychiatry. Bleuler was not a psychoanalyst himself but rather a
      pluridimensional psychiatrist in the best sense of the word and at the same time
      sympathetic to psychoanalysis. The reception and historical effect of Bleuler's
      work are described. Another important subject that Bleuler himself regarded as
      the central field in his work is pointed out: the fight against alcoholism.

PMID- 18058082
TI  - [Chronic spinal subdural hematoma].
AB  - Compared with spinal epidural hematomas, spinal subdural hematomas are rare;
      chronic forms are even more uncommon. These hematomas are associated not only
      with lumbar puncture and spinal trauma, but also with coagulopathies, vascular
      malformations and tumors. Compression of the spinal cord and the cauda equina
      means that the patients develop increasing back or radicular pain, followed by
      paraparesis and bladder and bowel paralysis, so that in most cases surgical
      decompression is carried out. On magnetic resonance imaging these hematomas
      present as thoracic or lumbar subdural masses, their signal intensity varying
      with the age of the hematoma. We report the clinical course and the findings
      revealed by imaging that led to the diagnosis in three cases of chronic spinal
      subdural hematoma.

PMID- 18058083
TI  - Non-alcoholic fatty liver disease is independently associated with an increased
      prevalence of chronic kidney disease and proliferative/laser-treated retinopathy
      in type 2 diabetic patients.
AB  - AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) is associated with an
      increased risk of cardiovascular disease in type 2 diabetes. Currently, there is
      a lack of information on associations between NAFLD and microvascular
      complications of diabetes. We assessed the associations between NAFLD and both
      chronic kidney disease (CKD) and retinopathy in a large cohort of type 2 diabetic
      individuals using a cross-sectional design. METHODS: Prevalence rates of
      retinopathy (by ophthalmoscopy) and CKD (defined as overt proteinuria and/or
      estimated GFR <or= 60 ml min(-1) 1.73 m(-2)) were assessed in 2,103 type 2
      diabetic individuals who were free of diagnosed cardiovascular disease and viral
      hepatitis. NAFLD was ascertained by patient history, blood sampling and liver
      ultrasound. RESULTS: NAFLD patients had higher (p<0.001) age- and sex-adjusted
      prevalence rates of both non-proliferative (39 vs 34%) and proliferative/laser
      treated retinopathy (11 vs 5%), and CKD (15 vs 9%) than counterparts without
      NAFLD. In logistic regression analysis, NAFLD was associated with increased rates
      of CKD (odds ratio 1.87; 95% CI 1.3-4.1, p=0.020) and proliferative/laser-treated
      retinopathy (odds ratio 1.75; 1.1-3.7, p=0.031) independently of age, sex, BMI,
      waist circumference, hypertension, diabetes duration, HbA(1c), lipids, smoking
      status and medications use. CONCLUSIONS/INTERPRETATION: Our findings suggest that
      NAFLD is associated with an increased prevalence of CKD and proliferative/laser
      treated retinopathy in type 2 diabetic individuals independently of numerous
      baseline confounding factors. Further studies are required to confirm the
      reproducibility of these results and to evaluate whether NAFLD contributes to the
      development or progression of CKD and retinopathy.

PMID- 18058084
TI  - Heparanase induces a differential loss of heparan sulphate domains in overt
      diabetic nephropathy.
AB  - AIMS/HYPOTHESIS: Recent studies suggest that loss of heparan sulphate in the
      glomerular basement membrane (GBM) of the kidney with diabetic nephropathy is due
      to the increased production of heparanase, a heparan sulphate-degrading
      endoglycosidase. Our present study addresses whether heparan sulphate with
      different modifications is differentially reduced in the GBM and whether
      heparanase selectively cleaves heparan sulphate with different domain
      specificities. METHODS: The heparan sulphate content of renal biopsies (14
      diabetic nephropathy, five normal) were analysed by immunofluorescence staining
      with four anti-heparan sulphate antibodies: JM403, a monoclonal antibody (mAb)
      recognising N-unsubstituted glucosamine residues; two phage display-derived
      single chain antibodies HS4C3 and EW3D10, defining sulphated heparan sulphate
      domains; and anti-K5 antibody, an mAb recognising unmodified heparan sulphate
      domains. RESULTS: We found that modified heparan sulphate domains (JM403, HS4C3
      and EW3D10), but not unmodified domains (anti-K5) and agrin core protein were
      reduced in the GBM of kidneys from patients with diabetic nephropathy, compared
      with controls. Glomerular heparanase levels were increased in diabetic
      nephropathy kidneys and inversely correlated with the amounts of modified heparan
      sulphate domains. Increased heparanase production and loss of JM403 staining in
      the GBM correlated with the severity of proteinuria. Loss of modified heparan
      sulphate in the GBM as a result of degradation by heparanase was confirmed by
      heparan sulphate staining of heparanase-treated normal kidney biopsy specimens.
      CONCLUSIONS/INTERPRETATION: Our data suggest that loss of modified heparan
      sulphate in the GBM is mediated by an increased heparanase presence and may play
      a role in the pathogenesis of diabetes-induced proteinuria.

PMID- 18058086
TI  - Does ligament balancing technique affect kinematics in rotating platform, PCL
      retaining knee arthroplasties? A prospective randomized study.
AB  - The goal of this prospective, randomized, blinded trial was to determine if
      ligament balancing techniques for rotating platform TKA affect postoperative knee
      kinematics. Sixteen patients with unilateral rotating platform TKA consented to
      participate in this institutional review board approved study. Eight patients
      were randomly selected to receive ligament balancing with an instrumented joint
      spreader device and eight patients received ligament balancing using fixed
      thickness spacer blocks. A single plane shape matching technique was used for
      kinematic analysis of static deep knee flexion and dynamic stair activities.
      There were no differences in knee kinematics between groups during static deep
      flexion activities. The spreader group demonstrated kinematics more similar to
      the normal knee during the ascending phase of the dynamic stair activity. Knee
      kinematics in static knee flexion were unaffected by ligament balancing
      technique, while knees balanced with the spreader demonstrated a medial pivot
      motion pattern during stair ascent. This medial pivot motion pattern may improve
      long-term results by more closely replicating normal knee kinematics.

PMID- 18058087
TI  - Dose-finding study of paliperidone ER based on striatal and extrastriatal
      dopamine D2 receptor occupancy in patients with schizophrenia.
AB  - RATIONALE: Paliperidone ER is a novel antipsychotic drug in an extended-release
      (ER) formulation. As with all antipsychotics, careful dose setting is necessary
      to avoid side effects. OBJECTIVES: In this study, we measured striatal and
      extrastriatal dopamine D2 receptor occupancy during paliperidone ER treatment in
      patients with schizophrenia using positron emission tomography (PET) to compare
      regional occupancy and to estimate the optimal dose. MATERIALS AND METHODS:
      Thirteen male patients with schizophrenia participated in this 6-week multiple
      dose study. Six of them took 3 mg of paliperidone ER per day, four took 9 mg, and
      three took 15 mg. Two to 6 weeks after first drug intake, two PET scans, one with
      [11C]raclopride and one with [11C]FLB 457, were performed in each patient on the
      same day. The relationship between the dose or plasma concentration of
      paliperidone and dopamine D2 receptor occupancy was calculated. RESULTS: The
      dopamine D2 receptor occupancies in the striatum measured with [11C]raclopride
      and the temporal cortex measured with [11C]FLB 457 were 54.2-85.5% and 34.5
      87.3%, respectively. ED50 values of the striatum and temporal cortex were 2.38
      and 2.84 mg/day, respectively. There was no significant difference in dopamine D2
      receptor occupancy between the striatum and the temporal cortex. CONCLUSIONS: The
      data from this study suggest that paliperidone ER at 6-9 mg provides an estimated
      level of dopamine D2 receptor occupancy between 70-80% and that the magnitude of
      dopamine D2 receptor occupancy is similar between the striatum and temporal
      cortex.

PMID- 18058085
TI  - Surviving Sepsis Campaign: international guidelines for management of severe
      sepsis and septic shock: 2008.
AB  - OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign
      clinical management guidelines, "Surviving Sepsis Campaign guidelines for
      management of severe sepsis and septic shock," published in 2004. DESIGN:
      Modified Delphi method with a consensus conference of 55 international experts,
      several subsequent meetings of subgroups and key individuals, teleconferences,
      and electronic-based discussion among subgroups and among the entire committee.
      This process was conducted independently of any industry funding. METHODS: We
      used the GRADE system to guide assessment of quality of evidence from high (A) to
      very low (D) and to determine the strength of recommendations. A strong
      recommendation indicates that an intervention's desirable effects clearly
      outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak
      recommendations indicate that the tradeoff between desirable and undesirable
      effects is less clear. The grade of strong or weak is considered of greater
      clinical importance than a difference in letter level of quality of evidence. In
      areas without complete agreement, a formal process of resolution was developed
      and applied. Recommendations are grouped into those directly targeting severe
      sepsis, recommendations targeting general care of the critically ill patient that
      are considered high priority in severe sepsis, and pediatric considerations.
      RESULTS: Key recommendations, listed by category, include: early goal-directed
      resuscitation of the septic patient during the first 6 hrs after recognition
      (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed
      promptly to confirm potential source of infection (1C); administration of broad
      spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and
      severe sepsis without septic shock (1D); reassessment of antibiotic therapy with
      microbiology and clinical data to narrow coverage, when appropriate (1C); a usual
      7-10 days of antibiotic therapy guided by clinical response (1D); source control
      with attention to the balance of risks and benefits of the chosen method (1C);
      administration of either crystalloid or colloid fluid resuscitation (1B); fluid
      challenge to restore mean circulating filling pressure (1C); reduction in rate of
      fluid administration with rising filing pressures and no improvement in tissue
      perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain
      an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine
      inotropic therapy when cardiac output remains low despite fluid resuscitation and
      combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given
      only in septic shock after blood pressure is identified to be poorly responsive
      to fluid and vasopressor therapy (2C); recombinant activated protein C in
      patients with severe sepsis and clinical assessment of high risk for death (2B
      except 2C for post-operative patients). In the absence of tissue hypoperfusion,
      coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL
      (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure
      strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome
      (ARDS); application of at least a minimal amount of positive end-expiratory
      pressure in acute lung injury (1C); head of bed elevation in mechanically
      ventilated patients unless contraindicated (1B); avoiding routine use of
      pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical
      ventilation and ICU length of stay, a conservative fluid strategy for patients
      with established ALI/ARDS who are not in shock (1C); protocols for weaning and
      sedation/analgesia (1B); using either intermittent bolus sedation or continuous
      infusion sedation with daily interruptions or lightening (1B); avoidance of
      neuromuscular blockers, if at all possible (1B); institution of glycemic control
      (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C );
      equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis
      (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis
      to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors
      (1B); and consideration of limitation of support where appropriate (1D).
      Recommendations specific to pediatric severe sepsis include: greater use of
      physical examination therapeutic end points (2C); dopamine as the first drug of
      choice for hypotension (2C); steroids only in children with suspected or proven
      adrenal insufficiency (2C); a recommendation against the use of recombinant
      activated protein C in children (1B). CONCLUSION: There was strong agreement
      among a large cohort of international experts regarding many level 1
      recommendations for the best current care of patients with severe sepsis.
      Evidenced-based recommendations regarding the acute management of sepsis and
      septic shock are the first step toward improved outcomes for this important group
      of critically ill patients.

PMID- 18058088
TI  - Bidirectional cannabinoid modulation of social behavior in adolescent rats.
AB  - RATIONALE: Marijuana use in adolescents is a highly social activity, and
      interacting endocannabinoid and opioid systems may modulate social reward.
      However, cannabinoid exposure has been reported to reduce social behavior.
      OBJECTIVES: The aim of this study was to elucidate the mechanisms underlying the
      paradoxical relationship between cannabinoid exposure and sociability. MATERIALS
      AND METHODS: We investigated the effect of cannabinoid agonists with a different
      mechanism of action on social play behavior in adolescent rats. In addition, we
      examined whether endocannabinoid neurotransmission interacts with opioid and
      dopaminergic neurotransmission in the modulation of social play behavior.
      RESULTS: The direct CB1 cannabinoid receptor agonist WIN55,212-2 reduced social
      play. However, the indirect cannabinoid agonist URB597, which inhibits the
      hydrolysis of the endocannabinoid anandamide, enhanced social play. This effect
      of URB597 depended upon stimulation of opioid and dopamine receptors. The well
      known stimulatory effect of morphine on social play was attenuated by the CB1
      cannabinoid receptor antagonist SR141716A, but independent of dopamine receptor
      stimulation. Combined treatment with ineffective doses of URB597 and morphine
      increased social play. CONCLUSIONS: Cannabinoid neurotransmission can both
      enhance and inhibit social interaction in adolescent rats depending on how the
      endocannabinoid system is stimulated. Activation of cannabinoid receptors
      throughout the brain, which occurs during cannabis use, inhibits sociability. In
      contrast, on-demand release of endocannabinoids facilitates social interaction,
      which is magnified by indirect cannabinoid agonists through an interaction with
      opioid and dopaminergic neurotransmission. These results shed light on the
      paradoxical relationship between cannabis exposure and sociability and suggest
      that endocannabinoid degradation inhibitors hold promise for the treatment of
      social dysfunctions.

PMID- 18058091
TI  - Heteroatom(isotope)-tagged genomics and proteomics.

PMID- 18058089
TI  - Models and mechanisms of anxiety: evidence from startle studies.
AB  - RATIONALE: Preclinical data indicates that threat stimuli elicit two classes of
      defensive behaviors, those that are associated with imminent danger and are
      characterized by flight or fight (fear), and those that are associated with
      temporally uncertain danger and are characterized by sustained apprehension and
      hypervigilance (anxiety). OBJECTIVE: The objectives of the study are to (1)
      review evidence for a distinction between fear and anxiety in animal and human
      experimental models using the startle reflex as an operational measure of
      aversive states, (2) describe experimental models of anxiety, as opposed to fear,
      in humans, (3) examine the relevance of these models to clinical anxiety.
      RESULTS: The distinction between phasic fear to imminent threat and sustained
      anxiety to temporally uncertain danger is suggested by psychopharmacological and
      behavioral evidence from ethological studies and can be traced back to distinct
      neuroanatomical systems, the amygdala and the bed nucleus of the stria
      terminalis. Experimental models of anxiety, not fear, are relevant to non-phobic
      anxiety disorders. CONCLUSIONS: Progress in our understanding of normal and
      abnormal anxiety is critically dependent on our ability to model sustained
      aversive states to temporally uncertain threat.

PMID- 18058090
TI  - Escitalopram effects on insula and amygdala BOLD activation during emotional
      processing.
AB  - RATIONALE: The amygdala and insular cortex are integral to the processing of
      emotionally salient stimuli. We have shown in healthy volunteers that an
      anxiolytic agent, lorazepam, dose-dependently attenuates activation of limbic
      structures. OBJECTIVE: The current study investigated whether administration of a
      selective serotonin reuptake inhibitor (SSRI), escitalopram, alters the
      activation of limbic structures. We hypothesized that subchronic (21 days) SSRI
      treatment attenuates the activation of the amygdala and insula during processing
      of emotional faces. MATERIALS AND METHODS: Thirteen healthy volunteers
      participated in a double-blind, placebo-controlled, crossover, randomized study.
      After 21 days of treatment with either escitalopram or placebo, participants
      underwent functional magnetic resonance imaging (fMRI) during which all subjects
      completed an emotion face assessment task, which has been shown to elicit
      amygdala and insula activation. RESULTS: Subjects activated the bilateral insula
      and amygdala after treatment with both escitalopram and placebo. In subjects who
      were adherent to the protocol (as evidenced by sufficiently high urine
      concentrations of escitalopram), a reduction in amygdala activation was seen in
      the escitalopram condition compared to placebo. CONCLUSION: The current
      investigation provides further evidence for the mechanism of action of SSRIs
      through the attenuation of activation in brain regions responsible for emotion
      processing and provides support for the use of blood oxygenation level-dependent
      fMRI with pharmacological probes to help identify the specific therapeutic effect
      of these agents in patients with anxiety and mood disorders.

PMID- 18058092
TI  - Distribution of the GNB3 825C>T polymorphism among Brazilians: impact of
      population structure.
AB  - OBJECTIVE: To describe the impact of population admixture on the distribution of
      the GNB3 825C>T polymorphism in the heterogeneous Brazilian population. METHODS:
      Individual DNA from 236 healthy Brazilians, self-identified as White,
      Intermediate and Black, was genotyped for a set of insertion/deletion
      polymorphisms that have been previously validated as ancestry informative markers
      (AIMs). The GNB3 825C>T polymorphism was detected by PCR-RFLP. Non-linear
      logistic regression modeling was applied to describe the association between the
      GNB3 825C>T polymorphisms and the African component of ancestry (ACA) estimated
      by the AIMs. RESULTS: The GNB3 825C>T allele and genotype distribution differed
      significantly across the three self-reported groups (P < 0.0001, chi(2) test),
      with a trend for increasing frequency of both the GNB3 825T allele and the TT
      genotype from White to Intermediate to Black individuals (P < 0.0001, chi(2) test
      for trend in proportions). Non-linear logistic regression showed that the odds of
      having the GNB3 825C>T allele increase monotonically (P < 0.0001, Wald
      statistics) with increasing ACA throughout the ACA range (0.136-0.897) observed
      in the overall population sample, irrespective of "racial/color" self
      identification. CONCLUSION: The present data on the GNB3 825C>T polymorphism
      support the notion that interethnic admixture, which is a source of spurious
      genotype-phenotype associations in pharmacogenetic/-genomic studies, must be
      dealt with as a continuous variable, rather than proportioned in arbitrary sub
      categories for the convenience of data quantification and analysis.

PMID- 18058093
TI  - Human cerebral cortices: signal variation on diffusion-weighted MR imaging.
AB  - INTRODUCTION: We have often encountered high signal intensity (SI) of the
      cingulate gyrus and insula during diffusion-weighted magnetic resonance imaging
      (DW-MRI) on neurologically healthy adults. To date, cortical signal heterogeneity
      on DW images has not been investigated systematically. The purpose of our study
      was to determine whether there is regional signal variation in the brain cortices
      of neurologically healthy adults on DW-MR images. METHODS: The SI of the cerebral
      cortices on DW-MR images at 1.5 T was evaluated in 50 neurologically healthy
      subjects (34 men, 16 women; age range 33-84 years; mean age 57.6 years). The
      cortical SI in the cingulate gyrus, insula, and temporal, occipital, and parietal
      lobes was graded relative to the SI of the frontal lobe. Contrast-to-noise ratios
      (CNRs) on DW-MR images were compared for each cortical area. Diffusion changes
      were analyzed by visually assessment of the differences in appearance among the
      cortices on apparent diffusion coefficient (ADC) maps. RESULTS: Increased SI was
      frequently seen in the cingulate gyrus and insula regardless of patient age.
      There were no significant gender- or laterality-related differences. The CNR was
      significantly higher in the cingulate gyrus and insula than in the other cortices
      (p< .01) , and significant differences existed among the cortical regions (p<
      .001). There were no apparent ADC differences among the cortices on ADC maps.
      CONCLUSION: Regional signal variation of the brain cortices was observed on DW-MR
      images of healthy subjects, and the cingulate gyrus and insula frequently
      manifested high SI. These findings may help in the recognition of cortical signal
      abnormalities as visualized on DW-MR images.

PMID- 18058094
TI  - Plantar vein thrombosis: a rare cause of plantar foot pain.
AB  - Plantar vein thrombosis is a rare condition, with only a handful of cases
      reported in the literature. The cause is unknown; however, the disease has been
      attributed to prior surgery, trauma, and paraneoplastic conditions. We present a
      case of a 32-year-old female runner with plantar vein thrombosis diagnosed on
      contrast-enhanced MRI and confirmed on ultrasound. The symptoms resolved with
      conservative treatment and evaluation revealed the presence of a prothrombin gene
      mutation and use of oral contraceptive pills. To our knowledge, this is the first
      case of plantar vein thrombosis diagnosed initially by MRI. Moreover, this case
      suggests that plantar vein thrombosis should be considered in patients with
      hypercoagulable states and plantar foot pain.

PMID- 18058095
TI  - Changes underlying the dynamic contrast-enhanced MRI response to treatment in
      rheumatoid arthritis.
AB  - OBJECTIVE: Dynamic contrast-enhanced MRI of patients with rheumatoid arthritis
      has shown a decrease in the early enhancement rate (EER) of synovitis after
      treatment. The purpose of this work was to investigate the underlying changes.
      METHODS: 3D dynamic contrast-enhanced images were acquired from 13 patients
      before and 1-2 weeks after anti-TNF alpha treatment. The EER of the inflamed
      synovium was measured. The T1 relaxation time of the synovitis was calculated
      from images at different flip angles. The time course of the arrival of
      gadolinium at the radial artery was determined. The gadolinium enhancement of the
      inflamed synovium was modeled to calculate the fractional plasma volume (vp), the
      fractional extravascular, extracellular fluid volume (ve), and the volume
      transfer constant (Ktrans). Pre- and post-treatment values were compared and the
      dependence of the EER on each parameter was assessed. RESULTS: There was a
      decrease in the EER measured over 26 s after treatment (29%, p = 0.002).
      Reductions in T1 (12%, p = 0.001), Ktrans (31%, p = 0.002), and vp (43%, p =
      0.01) contributed to this; however, the EER was relatively insensitive to changes
      in ve. CONCLUSIONS: The decrease in EER after anti-TNF alpha treatment is largely
      caused by reductions in the volume transfer constant Ktrans, the fractional
      plasma volume vp, and the T1 relaxation time. Only the contributions from Ktrans
      and vp directly reflect synovial vascularity.

PMID- 18058096
TI  - Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein
      derived macrophage-activating factor, GcMAF.
AB  - Serum vitamin D binding protein (Gc protein) is the precursor for the principal
      macrophage-activating factor (MAF). The MAF precursor activity of serum Gc
      protein of colorectal cancer patients was lost or reduced because Gc protein is
      deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from
      cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to
      immunosuppression. Stepwise treatment of purified Gc protein with immobilized
      beta-galactosidase and sialidase generated the most potent macrophage-activating
      factor (GcMAF) ever discovered, but it produces no side effect in humans.
      Macrophages treated with GcMAF (100 microg/ml) develop an enormous variation of
      receptors and are highly tumoricidal to a variety of cancers indiscriminately.
      Administration of 100 nanogram (ng)/ human maximally activates systemic
      macrophages that can kill cancerous cells. Since the half-life of the activated
      macrophages is approximately 6 days, 100 ng GcMAF was administered weekly to
      eight nonanemic colorectal cancer patients who had previously received tumor
      resection but still carried significant amounts of metastatic tumor cells. As
      GcMAF therapy progressed, the MAF precursor activities of all patients increased
      and conversely their serum Nagalase activities decreased. Since serum Nagalase is
      proportional to tumor burden, serum Nagalase activity was used as a prognostic
      index for time course analysis of GcMAF therapy. After 32-50 weekly
      administrations of 100 ng GcMAF, all colorectal cancer patients exhibited healthy
      control levels of the serum Nagalase activity, indicating eradication of
      metastatic tumor cells. During 7 years after the completion of GcMAF therapy,
      their serum Nagalase activity did not increase, indicating no recurrence of
      cancer, which was also supported by the annual CT scans of these patients.

PMID- 18058097
TI  - Tumors skew endothelial cells to disrupt NK cell, T-cell and macrophage
      functions.
AB  - INTRODUCTION: Patients and mice with solid tumors, such as Lewis lung carcinoma
      (LLC), have defects in functions of immune effector cells. Endothelial cells, a
      component of the tumor vasculature, are potential regulators of immune cell
      functions. Therefore, these studies examined the impact of exposure to LLC tumor
      on the ability of endothelial cells to modulate immune cell functions. MATERIALS
      AND METHODS: Endothelial cells were pre-treated with LLC tumor-conditioned medium
      (Endo(T-sup)) for 24 h. Control endothelial cells that were exposed to medium
      (Endo(Media)) epithelial cell-conditioned medium or (Endo(Epi-sup)). After the
      initial 24 h incubation, endothelial cells were washed and fresh media was added.
      Cells were allowed to incubate for an additional 24 h. Supernatants from
      Endo(Media), Endo(Epi-sup) or Endo(T-sup) were collected and assayed for immune
      modulatory products and for immune modulatory activity. RESULTS: Supernatant from
      Endo(T-sup) contained increased levels of PGE2, IL-6 and VEGF as compared to
      Endo(Media) and Endo(Epi-sup) controls. NK cell activity, as measured by TNF
      alpha and IFN-gamma secretion, was increased following exposure to media
      conditioned by Endo(Media) and Endo(Epi-sup) Exposure of NK cells to supernatants
      of Endo(T-sup), also increases TNF-alpha and IFN-gamma secretion, but to a lesser
      extent than by Endo(Media) and Endo(Epi-sup). Examination of macrophage functions
      demonstrated that supernatant from Endo(T-sup) decreased microbead phagocytosis
      and increased production of the immune suppressive mediators, IL-10 and PGE2.
      Lastly, T-cell responses to stimulation with anti-CD3 in the presence of
      supernatants from Endo(T-sup) were examined. IFN-gamma production by CD8+ T-cells
      was reduced after exposure to Endo(T-sup)-conditioned medium, as compared to
      cells treatments with medium or control conditioned medium. Production of IFN
      gamma by CD4+ T-cells exposed to Endo(T-sup) was not altered. CONCLUSIONS: Taken
      together, these studies demonstrate that tumors skew endothelial cells to disrupt
      NK cell, T-cell and macrophages functions, and represents a novel mechanism of
      tumor-induced immune suppression.

PMID- 18058098
TI  - A phase I safety, pharmacological, and biological study of the farnesyl protein
      transferase inhibitor, lonafarnib (SCH 663366), in combination with cisplatin and
      gemcitabine in patients with advanced solid tumors.
AB  - PURPOSE: This phase I study was conducted to evaluate the safety, tolerability,
      pharmacological properties and biological activity of the combination of the
      lonafarnib, a farnesylproteintransferase (FTPase) inhibitor, with gemcitabine and
      cisplatin in patients with advanced solid malignancies. EXPERIMENTAL DESIGN: This
      was a single institution study to determine the maximal tolerated dose (MTD) of
      escalating lonafarnib (75-125 mg po BID) with gemcitabine (750-1,000 mg/m(2) on
      days 1, 8, 15) and fixed cisplatin (75 mg/m(2) day 1) every 28 days. Due to dose
      limiting toxicities (DLTs) of neutropenia and thrombocytopenia in initial
      patients, these patients were considered "heavily pre-treated" and the protocol
      was amended to limit prior therapy and re-escalate lonafarnib in "less heavily
      pre-treated patients" on 28-day and 21-day schedules. Cycle 1 and 2
      pharmacokinetics (PK), and farnesylation of the HDJ2 chaperone protein and FPTase
      activity were analyzed. RESULTS: Twenty-two patients received 53 courses of
      therapy. Nausea, vomiting, and fatigue were frequent in all patients. Severe
      toxicities were observed in 91% of patients: neutropenia (41%), nausea (36%),
      thrombocytopenia (32%), anemia (23%) and vomiting (23%). Nine patients withdrew
      from the study due to toxicity. DLTs of neutropenia, febrile neutropenia,
      thrombocytopenia, and fatigue limited dose-escalation on the 28-day schedule. The
      MTD was established as lonafarnib 75 mg BID, gemcitabine 750 mg/m(2) days 1, 8,
      15, and cisplatin 75 mg/m(2) in heavily pre-treated patients. The MTD in the less
      heavily pre-treated patients could not be established on the 28-day schedule as
      DLTs were observed at the lowest dose level, and dose escalation was not
      completed on the 21-day schedule due to early study termination by the Sponsor.
      No PK interactions were observed. FTPase inhibition was not observed at the MTD,
      however HDJ-2 gel shift was observed in one patient at the 100 mg BID lonafarnib
      dose. Anti-cancer activity was observed: four patients had stable disease lasting
      >2 cycles, one subject had a complete response, and another had a partial
      response, both with metastatic breast cancer. CONCLUSION: Lonafarnib 75 mg BID,
      gemcitabine 750 mg/m(2) days 1, 8, 15, and cisplatin 75 mg/m(2) day 1 on a 28-day
      schedule was established as the MTD. Lonafarnib did not demonstrate FTPase
      inhibition at these doses. Despite the observed efficacy, substantial toxicity
      and questionable contribution of anti-tumor activity of lonafarnib to gemcitabine
      and cisplatin limits further exploration of this combination.

PMID- 18058099
TI  - TLR2 in murine atherosclerosis.
AB  - Atherosclerosis was once thought to be solely a disease of lipid accumulation in
      the vessel wall. It does involve lipid accumulation, but inflammation appears to
      be an important driving factor. Consequently, our laboratory undertook to examine
      the role(s) of TLRs, and especially TLR2, in murine models of atherosclerosis.

PMID- 18058100
TI  - Stationary multiple spots for reaction-diffusion systems.
AB  - In this paper, we review analytical methods for a rigorous study of the existence
      and stability of stationary, multiple spots for reaction-diffusion systems. We
      will consider two classes of reaction-diffusion systems: activator-inhibitor
      systems (such as the Gierer-Meinhardt system) and activator-substrate systems
      (such as the Gray-Scott system or the Schnakenberg model). The main ideas are
      presented in the context of the Schnakenberg model, and these results are new to
      the literature. We will consider the systems in a two-dimensional, bounded and
      smooth domain for small diffusion constant of the activator. Existence of multi
      spots is proved using tools from nonlinear functional analysis such as Liapunov
      Schmidt reduction and fixed-point theorems. The amplitudes and positions of spots
      follow from this analysis. Stability is shown in two parts, for eigenvalues of
      order one and eigenvalues converging to zero, respectively. Eigenvalues of order
      one are studied by deriving their leading-order asymptotic behavior and reducing
      the eigenvalue problem to a nonlocal eigenvalue problem (NLEP). A study of the
      NLEP reveals a condition for the maximal number of stable spots. Eigenvalues
      converging to zero are investigated using a projection similar to Liapunov
      Schmidt reduction and conditions on the positions for stable spots are derived.
      The Green's function of the Laplacian plays a central role in the analysis. The
      results are interpreted in the biological, chemical and ecological contexts. They
      are confirmed by numerical simulations.

PMID- 18058102
TI  - Identification and characterization of simple sequence repeat markers for Pythium
      aphanidermatum, P. cryptoirregulare, and P. irregulare and the potential use in
      Pythium population genetics.
AB  - Six simple sequence repeat (SSR)-enriched genome libraries from Pythium
      aphanidermatum, P. irregulare, and P. cryptoirregulare were constructed to
      develop SSR markers. One hundred six SSR primer pairs for P. aphanidermatum, 73
      for P. cryptoirregulare, and 82 for P. irregulare were initially identified.
      After examining primers, the most polymorphic and reproducible SSR markers were
      selected for each Pythium species; 14 in P. aphanidermatum, 21 in P. irregulare,
      and 22 in P. cryptoirregulare. Analysis of isolates from each Pythium species
      using SSR markers showed the high degree of gene diversity and polymorphic
      information content (PIC) value in the three species. The average number of
      alleles was 3.5-5.3 in the three Pythium species. Seven SSR loci from P.
      cryptoirregulare and P. irregualre showed the distinct genetic separations of P.
      irregualre complex isolates. SSR markers identified for the three Pythium target
      species were highly transferable to other closely related Pythium species. Cross
      amplification was found in all SSR markers between P. cryptoirregulare and P.
      irregulare. SSR loci were successfully amplified by direct PCR from mycelia of P.
      aphanidermatum, P. cryptoirregulare, and P. irregulare. These newly developed SSR
      markers can be used for population genetic studies and monitoring the movement of
      isolates in crop production systems or in nature.

PMID- 18058101
TI  - Mutations affecting spindle pole body and mitotic exit network function are
      synthetically lethal with a deletion of the nucleoporin NUP1 in S. cerevisiae.
AB  - Nuclear pore complexes (NPCs) are embedded in the nuclear envelope of eukaryotic
      cells and function to regulate passage of macromolecules in and out of the
      nucleus. Nup1 is one of 30 nucleoporins comprising the NPC of the yeast
      Saccharomyces cerevisiae and is located on the nucleoplasmic face of the NPC
      where it plays a role in mRNA export and protein transport. In order to further
      characterize the function of Nup1 we used a genetic approach to identify
      mutations that are synthetically lethal in combination with a deletion of NUP1
      (nup1Delta). We have identified one such nup1 lethal mutant (nle6) as a
      temperature sensitive allele of nud1. NUD1 encodes a component of the yeast
      spindle pole body (SPB) and acts as scaffolding for the mitotic exit network
      (MEN). We observe that nle6/nud1 mutant cells have a normal distribution of NPCs
      within the nuclear envelope and exhibit normal rates of nuclear protein import at
      both the permissive and restrictive temperatures. nup1Delta also exhibits
      synthetic lethality with bub2Delta and bfa1Delta, both of which encode proteins
      that colocalize with Nud1 at spindle pole bodies and function in the mitotic exit
      network. However, we do not observe genetic interactions among nle6/nud1,
      bub2Delta, or bfa1Delta and mutations in the nucleoporin encoding genes NUP60 or
      NUP170, nor is nup1Delta synthetically lethal with the absence of components
      downstream in the mitotic exit network, including Lte1, Swi5, and Dbf2. Our
      results suggest a novel functional connection between Nup1 and proteins
      comprising both the spindle pole body and early mitotic exit network.

PMID- 18058103
TI  - Isolation of mycoparasitic-related transcripts by SSH during interaction of the
      mycoparasite Stachybotrys elegans with its host Rhizoctonia solani.
AB  - Mycoparasitism by antagonistic fungi involves changes in the biochemistry and
      physiology of both partners. Analysis of genes that are expressed during
      mycoparasite-host interaction represents a powerful strategy to obtain insight
      into the molecular events underlying these changes. The aim of this study is to
      identify genes whose expression is upregulated when the mycoparasite Stachybotrys
      elegans is in direct confrontation with its host Rhizoctonia solani. Suppression
      subtractive hybridization (SSH) was used to create a subtracted cDNA library, and
      differential screening was applied to identify the over-expressed transcripts. We
      report the analysis of 2,166 clones, among which 47% were upregulated during
      mycoparasitism. Two hundred and sixty-one clones were sequenced that corresponded
      to 94 unique genes. Forty-four of these were identified as novel genes, while the
      remainder showed similarity to a broad diversity of genes with putative functions
      related to toxin production, pathogenicity, and metabolism. As a result of
      mycoparasitism, 15 genes belonged to R. solani among which 9 genes were assigned
      putative functions. Quantitative RT-PCR was used to examine the upregulation of
      12 genes during the course of mycoparasitism. Seven genes showed significant
      upregulation at least at one-time point during interaction of the mycoparasite
      with its host. This study describes a first step toward knowledge of S. elegans
      genome. The results present the useful application of EST analysis on S. elegans
      and provide preliminary indication of gene expression putatively involved in
      mycoparasitism.

PMID- 18058104
TI  - Unusual presentation of non-Hodgkin lymphoma: polyarthritis and uveitis mimicking
      a rheumatologic disease.
AB  - We report a case of 45-year-old male who presented with polyarthritis and
      posterior uveitis. He was given azathioprine (AZA) 150 mg day(-1) and methyl
      prednisolone 48 mg day(-1) for his uveitis and polyarthritis. Eye and joint
      complaints improved with these medications within 1 month. Three months later,
      while he was on AZA, the patient presented with pain on his anterior chest wall
      associated with diffuse hyperemic and warm mass lesion. A wedge biopsy of the
      lesion was reported as diffuse large B-cell NHL. Here, we briefly discuss the
      relationship between arthritis, uveitis and lymphoproliferative disease.

PMID- 18058105
TI  - Coping styles in fibromyalgia: effect of co-morbid posttraumatic stress disorder.
AB  - To analyze coping styles of fibromyalgia (FM) patients with specific emphasis on
      differences in coping styles between fibromyalgia patients with and without post
      traumatic stress disorder (PTSD). Seventy-seven consecutive patients (40 women
      and 37 men) who fulfilled ACR criteria for FM, and 48 healthy controls, completed
      questionnaires measuring prevalence and severity of PTSD symptoms, including the
      structured clinical interview for DSM-III-R-non-patient edition (SCID-NP) and the
      clinician administered PTSD scale (CAPS). Subjects were divided into two groups
      based on the presence or absence of PTSD symptoms. Subsequently, coping styles
      were measured using the Albert Einstein College of Medicine (AECOM) Coping Style
      Questionnaire. Student t tests were used to compare the means of quantitative
      variables, and proportions were compared by Chi square tests. Analysis of
      variance (ANOVA) was used to compare the scores of the FM patients with and
      without PTSD, as well as to estimate the effect of gender on psychiatric
      variables. FM patients exhibit significantly higher levels of suppression
      (P<0.00001), help-seeking (P<0.007), replacement (P<0.003), substitution
      (P<0.002), and reversal (P<0.004) compared with healthy controls. FM patients
      with PTSD and without PTSD differed significantly only on the suppression
      subscale (P<0.02). FM patients that have PTSD presented higher suppression scores
      compared to FM patients without PTSD. No significant difference was noted on
      scales of minimization, help-seeking, replacement, blame, substitution, mapping,
      and reversal. Our results have delineated coping patterns of FM patients,
      identifying suppression, help-seeking, replacement, substitution and replacement
      as strategies more common among these patients. We further identified suppression
      as the only coping style significantly more common among FM patients with co
      morbid PTSD then among FM patients without such a diagnosis. Our results may
      serve to further characterize cognitive and behavioral aspects of FM patients and
      subsequently guide therapeutic interventions.

PMID- 18058106
TI  - Benign nontraumatic osteolytic vertebral collapse simulating malignancy.
AB  - This study described the imaging features of a distinctive pattern of biopsy
      proven benign non-traumatic vertebral collapse (VC) that can mimic malignancy.
      Among 240 patients referred with painful VC over a 10-year period, we
      retrospectively selected 15 cases of benign VC which simulated malignancy, due to
      cortical bone destruction on radiographs. The diagnosis of benign origin was
      documented by percutaneous biopsy and 12-months of follow-up. Radiographs, CT and
      MR images of the spine were reviewed. Findings suggestive of malignancy included
      destruction involving the anterolateral cortex, posterior cortex and pedicles of
      the vertebral body (46%,15% and 15% respectively) at CT, epidural soft-tissue
      masses on CT (23%) and MR images (21%), and diffuse low signal-intensity (SI) of
      the vertebral body (50%) and pedicles (79%) on T1-weighted images. Features
      suggestive of a benign origin included an intravertebral vacuum phenomenon on
      radiographs and CT (13%), fracture lines within the vertebral body (92%) or
      pedicles (62%) at CT and presence an intravertebral area of high SI on T2
      weighted images (93%). Benign non-traumatic osteolytic VC can simulate malignancy
      on radiographs. The features, above mentioned on CT and MR suggestive of a benign
      VC, are useful in interpreting biopsy results of such lesions and avoiding
      unnecessary repeat biopsy.

PMID- 18058107
TI  - Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for
      a therapeutic strategy: comparison with intraoperative and histopathologic
      findings in focal liver lesions.
AB  - A multicenter study has been employed to evaluate the diagnostic efficacy of
      magnetic resonance imaging (MRI) using the new liver-specific contrast agent
      gadoxetic acid (Gd-EOB-DTPA, Primovist), as opposed to contrast-enhanced biphasic
      spiral computed tomography (CT), in the diagnosis of focal liver lesions,
      compared with a standard of reference (SOR). One hundred and sixty-nine patients
      with hepatic lesions eligible for surgery underwent Gd-EOB-DTPA-enhanced MRI as
      well as CT within 6 weeks. Pathologic evaluation of the liver specimen combined
      with intraoperative ultrasound established the SOR. Data sets were evaluated on
      site (14 investigators) and off-site (three independent blinded readers). Gd-EOB
      DTPA was well tolerated. Three hundred and two lesions were detected in 131
      patients valid for analysis by SOR. The frequency of correctly detected lesions
      was significantly higher on Gd-EOB-DTPA-enhanced MRI compared with CT in the
      clinical evaluation [10.44%; 95% confidence interval (CI): 4.88, 16.0]. In the
      blinded reading there was a trend towards Gd-EOB-DTPA-enhanced MRI, not reaching
      statistical significance (2.14%; 95% CI: -4.32, 8.6). However, the highest rate
      of correctly detected lesions with a diameter below 1 cm was achieved by Gd-EOB
      DTPA-enhanced MRI. Differential diagnosis was superior for Gd-EOB-DTPA-enhanced
      MRI (82.1%) versus CT (71.0%). A change in surgical therapy was documented in 19
      of 131 patients (14.5%) post Gd-EOB-DTPA-enhanced MRI. Gd-EOB-DTPA-enhanced MRI
      was superior in the diagnosis and therapeutic management of focal liver lesions
      compared with CT.

PMID- 18058108
TI  - Defining the role of NMP22 in bladder cancer surveillance.
AB  - Despite advances in treatment and knowledge of its pathogenesis, urothelial
      carcinoma of the bladder remains a significant cause of morbidity and mortality.
      Experience with the natural course of bladder cancer has revealed that early
      diagnosis of primary and recurrent disease improves patient prognosis. In this
      regard, cystoscopy (usually in combination with urinary cytology) has long been
      regarded as the gold standard for the diagnosis and surveillance of bladder
      cancer. However, the disadvantages inherent to cystoscopy, including invasiveness
      and cost, have stimulated a search for alternative methods for detecting
      urothelial malignancy. The ideal alternative test would duplicate the high
      accuracy of cystoscopy for detecting bladder tumors while eschewing its
      invasiveness, attendant morbidity, and high cost. The vast majority of bladder
      cancers arise from the urothelium, which continually sheds cells as well as
      intracellular contents into the urine, thereby providing a potential source of
      cancer-specific markers. Voided cytology and urinalysis are established tests
      that have been the standard tools for detection of such substances. The last
      decade has seen the rise of a myriad of novel urine-based bladder tumor markers,
      including bladder tumor antigen, urinary bladder cancer antigen, fibronectin,
      telomerase, and nuclear matrix proteins (e.g., NMP22). The NMP22 assay in
      particular has been the subject of considerable study and has demonstrated some
      promise as a potential adjunct to cystoscopy and cytology. Through a critical
      review of the literature, we seek to define the role, if any, of NMP22 in the
      follow-up of patients with a previous history of urothelial carcinoma of the
      bladder.

PMID- 18058109
TI  - [Congenital cranial dysinnervation disorders].
AB  - Congenital cranial dysinnervation disorders (CCDDs) are responsible for 1-2% of
      infant strabismus cases. Insufficient innervation and misinnervation of aberrant
      nerve fibres lead to motility restrictions and synkinesis. We present the most
      common CCDDs and explain their pathogenesis and the resulting clinical features.
      Furthermore, we emphasize essential diagnostic steps and treatment aspects.

PMID- 18058110
TI  - Increased urea synthesis and/or suppressed ammonia production in the African
      lungfish, Protopterus annectens, during aestivation in air or mud.
AB  - The objective of this study was to elucidate how the African lungfish,
      Protopterus annectens, ameliorated ammonia toxicity during 12 or 46 days of
      aestivation in air or in mud. Twelve days of aestivation in air led to
      significant increases in contents of urea, but not ammonia, in tissues of P.
      annectens. The estimated rate of urea synthesis increased 2.7-fold despite the
      lack of changes in the activities of hepatic ornithine-urea cycle enzymes, but
      there was only a minor change in the estimated rate of ammonia production. After
      46 days of aestivation in air, the ammonia content in the liver decreased
      significantly and contents of urea in all tissues studied increased
      significantly, indicating that the fish shifted to a combination of increased
      urea synthesis (1.4-fold of the day 0 value) and decreased ammonia production
      (56% of the day 0 value) to defend against ammonia toxicity. By contrast, 12 days
      of aestivation in mud produced only minor increases in tissue urea contents, with
      ammonia contents remained unchanged. This was apparently achieved through
      decreases in urea synthesis and ammonia production (40 and 15%, respectively, of
      the corresponding day 0 value). Surprisingly, 46 days of aestivation in mud
      resulted in no changes in tissue urea contents, indicating that profound
      suppressions of urea synthesis and ammonia production (2.6 and 1.2%,
      respectively, of the corresponding day 0 value) had occurred. This is the first
      report on such a phenomenon, and the reduction in ammonia production was so
      profound that it could be the greatest reduction known among animals. Since fish
      aestivated in mud had relatively low blood pO(2) and muscle ATP content, they
      could have been exposed to hypoxia, which induced reductions in metabolic rate
      and ammonia production. Consequently, fish aestivating in mud had a lower
      dependency on increased urea synthesis to detoxify ammonia, which is energy
      intensive, than fish aestivating in air.

PMID- 18058111
TI  - Outcomes after surgery for focal epilepsy in children.
AB  - OBJECT: Surgery is an effective treatment for selected patients with intractable
      epilepsy. The authors report the outcomes of focal resection in a series of
      children suffering from intractable focal epilepsy treated at a single
      institution. METHODS: The authors retrospectively analyzed a series of 58
      consecutive children who underwent surgery between 1998 and 2006 for intractable
      localized epilepsy at Primary Children's Medical Center. Evaluation for surgery
      and follow-up was performed by the authors in the combined Pediatric Epilepsy
      Surgery Clinic. RESULTS: Preoperative seizure duration ranged from 6 months to 15
      years. The cause of epilepsy was mesial temporal sclerosis (MTS) in 16 patients,
      dual pathology (MTS plus another lesion) in 3 patients, low-grade tumors in 16
      patients, cortical dysplasia (CD) in 13 patients, cavernous malformation (CM) in
      5 patients, and other conditions in 5 patients. In 33 cases, the lesions were in
      the temporal lobe, and in 25 cases, the lesions were extratemporal. At last
      follow-up, 74% (43/58) of all patients were seizure-free; seizure-free rates for
      specific conditions were 88% (14/16) for MTS, 33% (1/3) for dual pathology, 81%
      (13/16) for tumor, 62% (8/13) for CD, and 80% (4/5) for CM. Seizure-free rates
      were 85% (28/33) for temporal locations and 60% (15/25) for extratemporal
      locations. There were no permanent neurological complications or deaths.
      CONCLUSION: Surgery for localized epilepsy in carefully selected children has
      good seizure control rates with minimal complications. Outcomes for patients with
      resections in temporal locations were better than those for patients with
      extratemporal resections.

PMID- 18058112
TI  - Femoral fit in ABG-II hip stems, influence on clinical outcome and bone
      remodeling: a radiographic study.
AB  - INTRODUCTION: In a consecutive series of 64 patients with an ABG-II stem, we
      analyzed whether the tightness of the fit of the prosthesis affected bone
      remodeling and if there was a relation between clinical and radiological results.
      MATERIALS AND METHODS: Radiographic analysis of bone remodeling in different
      Gruen zones was done. Bone density changes were graded as present or absent in
      the AP and lateral radiographs as compared with the previous sets of radiographs.
      Bone remodeling was compared to literature values of the ABG-I stem. Three stem
      levels were defined. The proximal level was set at the upper border of the lesser
      trochanter, the mid-stem level at halfway the stem and the distal level 1 cm
      above the tip of the prosthesis. Femoral fit was defined as tight when the ratio
      of the fit was >/=0.8 and as non-tight if the fit was <0.8. The incidence of
      thigh pain was scored using the Merle d'Aubigne (MdA) hip score. RESULTS:
      Proximal bone resorption in Gruen zone 1 was 26.6% and in zone 7, 34.4% compared
      to 48 and 45% for the ABG-I stem after 5 years. No correlation was found between
      femoral fit and radiological changes. Proximal and distal fit was significantly
      lower for patients with thigh pain than without thigh pain. Patients with a non
      tight proximal fit produced significantly more varus (17/30 = 56.7%) than
      patients with a tight proximal fit (2/34 = 5.9%; P < 0.01). CONCLUSION: Femoral
      fit in ABG-II does not predict certain radiological changes, but less proximal
      bone resorption confirms the design changes from ABG-I to ABG-II. A non-tight
      proximal fit is correlated with varus position of the stem. Thigh pain is
      correlated with a poor fit and fill of the femoral stem.

PMID- 18058114
TI  - Arthroscopic double-pulley suture-bridge technique for rotator cuff repair.
AB  - After preparation of the bone bed, two doubly loaded suture anchors with suture
      eyelets are inserted at the articular margin of the greater tuberosity. A
      retrograde suture-passing instrument penetrates the rotator cuff to retrieve the
      sutures through the modified Neviaser or subclavian portal. An ipsilateral pair
      of suture eyelets in the suture anchor is passed through the margins of the
      rotator cuff tear. The blue suture of the second and third pair is pulled out of
      the lateral cannula, and the threaded blue suture of the third pair in the needle
      is passed through the blue suture of the second pair. After retrieving the blue
      suture of the first pair through the anterior portal, it is pulled out to pass
      the blue suture of the third pair through the eyelet of the anteromedial anchor.
      The blue suture is linked between two anchors. The medial row of suture-bridge is
      repaired with a sliding knot, and the sutures are not cut. Once the rotator cuff
      repair using the suture-bridge technique has been performed, the two blue strands
      in the anterior portal are tied. We describe our technique that possesses the
      advantages of both the double-pulley and suture-bridge techniques, which improves
      the pressurized contact area and maximizes compression along the medial row.

PMID- 18058113
TI  - Soft tissue necrosis following using calcium phosphate cement in calcaneal bone
      cyst: case report.
AB  - Calcium phosphate cements have received widespread attention for their possible
      role as bone-grafting material and bone fillers in skeletal defects. They were
      evaluated as a biomaterial in many aspects. No serious harmful effects such as
      foreign body reaction and tissue necrosis against to calcium phosphate cements
      have been reported yet. They were accepted as highly biocompatible materials. In
      this paper, we represent a patient who had soft tissue necrosis around lateral
      malleolar region, following using percutaneous calcium phosphate cement as a
      filler bone substitute in calcaneus bone cyst. The possible mechanisms were
      discussed.

PMID- 18058115
TI  - Sagittal plane analysis of the open and closed methods in children with displaced
      supracondylar fractures of the humerus (a radiological study).
AB  - OBJECTIVES: The aim of this study was to compare the radiological outcome of open
      and close reduction and osteosynthesis methods in the treatment of type II and
      III supracondylar humerus fractures in childhood with respect to the immediate
      post-operative reduction quality in sagittal plane. METHOD: One hundred and forty
      four-pediatric patients with type IIb and III supracondylar humerus fractures
      treated at two centers between 1995 and 2005 were evaluated radiologically within
      a retrospective study. Seventy-six patients (54 boys, 22 girls, mean age 7.6,
      range 2-12) were treated by closed reduction and cross percutaneous pinning while
      68 (49 boys, 19 girls, mean age 7.3, range 2-13) were treated by open reduction.
      The reduction quality of the open and closed groups was compared on immediate
      post-operative lateral radiographs by measuring of lateral humerocapitellar
      angle, anterior humeral line and anterior coronoid line criteria. The reduction
      quality was classified excellent, good, fair and poor according to the
      achievement of three, two, one or none of the criteria, respectively. Reductions
      classified as excellent and good were introduced as acceptable results. RESULTS:
      At least one criterion was achieved in all the patients of both the groups. The
      mean humerocapitellar angle was 30.1 degrees in closed reduction group while the
      mean of it was 29.8 degrees in open reduced group. Radiograph of 48 (63.1%)
      patients with closed reduction were found to display the anterior humeral line
      intersecting the middle one-third of capitellum while this criteria was 45 (66%)
      in open reduction group. The anterior coronoid line was disturbed in three
      patients in each of both the groups. The reduction quality was evaluated to be
      excellent in 32 patients, good in 31, fair in 13 at the closed reduction group
      while these evaluations were 31, 20 and 17 in open reduction group, respectively.
      Successful reduction was achieved in 74.9% of the patients in closed reduction
      group and 75% of the patients in open reduction group. CONCLUSION: It is
      concluded that there was no significant difference between closed and open
      reductions of pediatric displaced supracondylar fractures with regard to the
      radiological criteria of reduction quality in sagittal plane.

PMID- 18058116
TI  - A new hinged dynamic distractor, for immediate mobilization after knee
      dislocations: Technical note.
AB  - Knee dislocation is always a difficult topic mainly with regard to the structures
      that have been damaged and the best treatment option. The purpose of this study
      is to describe a new dynamic external fixator (EF) to be applied after knee
      dislocation, in combination with posterior cruciate ligament (PCL)
      reconstruction. This approach permits an immediate postoperative mobilization of
      the joint, with the possibility to perform a delayed ACL reconstruction and
      eventually reducing the complication rate related to multiple ligament surgery.

PMID- 18058117
TI  - "Minimized rotational vestibular testing" as a screening procedure detecting
      vestibular areflexy in deaf children: screening cochlear implant candidates for
      Usher syndrome type I.
AB  - Morbus Usher (USH), a combination of sensorineural hearing loss and retinal
      visual impairment, is classified into group I-III. USH I patients are born deaf.
      Within the first 10 years of life, they develop a severe vision impairment due to
      progressive retinal dystrophy (retinitis pigmentosa). USH I patients show
      vestibular deficits. The incidence of USH I among congenitally deaf children is
      assumed to be as high as 10%. We intend to create a simple examination procedure
      for screening congenitally deaf children for vestibular deficiency and
      subsequently USH I. The examination procedure is named "Minimized Rotation". The
      vestibular function of deaf children was examined by Minimized Rotation during
      their preoperative cochlear implant candidacy examination. A lack of
      postrotational nystagmus was seen as an indication for vestibular deficit.
      Subsequently some of these patients were examined under general anaesthesia by
      electroretinography (ERG) at the Department of Ophthalmology. A total of 117
      children were examined by Minimized Rotation. In 19 children (16.2%) no
      rotational nystagmus was found. Six of these children were additionally examined
      at the Department of Ophthalmology using Ganzfeld ERG. Three of them (50%) showed
      generalized dysfunction of the retina; 8.1% of the children undergoing
      preoperative evaluation for cochlear implatation are assumed to show
      abnormalities of the retina. Rotational examination seems to be an appropriate
      screening method to detect vestibular deficits, which is one sign of USH I. The
      results always have to be verified by Ganzfeld-ERG or further genetic
      investigations. Children with USH I are threatened by progressive reduction of
      vision. We, therefore, consider USH I children always to be implanted bilaterally
      with a cochlear implant to maximize the benefit of auditory rehabilitation.

PMID- 18058118
TI  - Production of cytokines by peritoneal macrophages and splenocytes after exposures
      of mice to low doses of X-rays.
AB  - We have shown previously that irradiations of mice with 0.1 or 0.2 Gy of X-rays
      stimulate anti-tumour cytotoxic activities of peritoneal macrophages and
      splenocytes enriched for NK lymphocytes and suppress the development of pulmonary
      tumour colonies. The up-regulated cytotoxicities were related to the production
      of nitric oxide by macrophages, and perforin and Fas ligand by the splenocytes,
      but specific blockade of these pathways did not totally suppress the effector
      cell-mediated cytolysis of the tumour target. Hence, other factors such as
      cytotoxic/cytostatic cytokines might have been produced by the effector cells. To
      test this possibility peritoneal macrophages and splenocytes were isolated from
      BALB/c mice which had been either once or tentimes whole body-irradiated with the
      total doses of 0.1 and 0.2 Gy of X-rays and assayed for the levels of IL-1beta,
      IL-2, IL-12, IFN-gamma and TNF-alpha in the incubation medium using the
      respective ELISA kits. The results demonstrate that both single and multiple
      exposures to the two low doses of X-rays significantly stimulate secretion of IL
      1beta, TNF-alpha and IL-12 by macrophages and IL-2 and IFN-gamma by splenocytes,
      but the kinetics and magnitude of the induced changes in the production of these
      cytokines differ between the two irradiation protocols.

PMID- 18058119
TI  - Molecular and cytogenetic evidence for an allotetraploid origin of Trifolium
      dubium (Leguminosae).
AB  - Suckling clover, Trifolium dubium Sibth., is a European grassland legume that has
      spread to many parts of the world. The present work shows that it is an
      allotetraploid (2n = 4x = 30) combining the genomes of T. campestre Schreb. (2n =
      2x = 14) and T. micranthum Viv. (2n = 2x = 16), two diploid species of similar
      geographic distribution. T. dubium has two nuclear ITS sequences that closely
      match those of T. campestre and T. micranthum. Genomic in situ hybridisation
      using genomic DNA of T. campestre and T. micranthum as probes has differentiated
      the ancestral sets of chromosomes in T. dubium cells. Comparative fluorescence in
      situ hybridisation analyses of 5S and 18S-26S rDNA loci were also consistent with
      an allotetraploid structure of the T. dubium genome. A marked preponderance of
      ITS repeats from T. campestre over those from T. micranthum indicated that
      concerted evolution has resulted in partial homogenisation of these sequences by
      depletion of the T. micranthum-derived 18S-26S rDNA repeats. In parallel with
      this, the epigenetic phenomenon of nucleolar dominance has been observed in T.
      dubium such that the chromatin associated with the 18S-26S rDNA loci derived from
      T. campestre is decondensed (transcriptionally active), whilst that from T.
      micranthum remains highly condensed throughout the cell cycle. T. dubium,
      therefore, appears to have arisen by way of hybridisation between forms of the
      diploid species T. campestre and T. micranthum accompanied by chromosome
      doubling. The observed genomic changes in rDNA resulting from interspecific
      hybridisation provide evidence for the process of genome diploidisation in T.
      dubium.

PMID- 18058120
TI  - Prevalence of self-reported symptoms and consequences related to inhalation of
      airborne chemicals in a Danish general population.
AB  - OBJECTIVE: To estimate the prevalence and consequences of self-reported symptoms
      related to inhalation of airborne chemicals in a Danish general population.
      METHODS: A random sample of 18-69-year-old individuals (n = 6,000) was drawn from
      the Danish Civil Registration System. A questionnaire on self-reported symptoms
      related to inhalation of 11 categories of airborne chemicals was mailed to the
      population. Respondents who reported symptoms received an additional
      questionnaire to verify the reported symptoms and to characterise factors related
      to the initial onset of symptoms. RESULTS: The response rate to the primary
      questionnaire was 71%. A total of 1,134 individuals (27%, 95% CI 25-28) reported
      symptoms related to inhalation of airborne chemicals, 141 individuals (3.3%, 95%
      CI 2.8-3.9) reported adjustments of social life or occupational conditions due to
      symptoms, whereas 20 individuals (0.5%, 95% CI 0.3-0.7) had made adjustments of
      both social life and occupational conditions. Women reported more exposures as
      annoying than men and had more symptoms related to inhalation of airborne
      chemicals (P < 0.001). However, sex had no effect on the reporting of adjustments
      of social life or occupational conditions (P = 0.54). CONCLUSION: Symptoms
      related to inhalation of airborne chemicals were common in this general
      population, and a minority reported that these symptoms affected social life or
      occupational conditions. Women as compared to men reported more symptoms but not
      adjustments of social life or occupational conditions.

PMID- 18058121
TI  - Spontaneous abortions in female populations occupationally exposed to ionizing
      radiation.
AB  - OBJECTIVE: Exposure to radioisotopes of metals and halogen elements occurring in
      medical practice may cause spontaneous abortions. The potential role of
      occupational exposure to X-rays and internal radioisotopes on pregnancy outcome
      in childbearing age women employed in hospital departments were analyzed in order
      to estimate miscarriage risk. METHODS: Over a period of 16 years, the occurrence
      of miscarriages in 61 women exposed to radioisotopes was compared to that
      reported in 170 X-ray exposed women. Chromosomal aberrations (CA) were measured
      in both radiation-exposed groups and in 53 non-exposed women. RESULTS: Women
      exposed to radioisotopes experienced at least a threefold higher rate of
      spontaneous abortions than those exposed to X-ray (OR = 3.68, 95% CI = 1.39-9.74,
      P < 0.01). Although X-ray and radioisotopes exposed women had significantly
      higher levels of chromosome type frequency (0.51 +/- 0.82, and 0.63 +/- 0.99,
      respectively) than referents (0.17 +/- 0.34), there was no clear difference
      between radiation-exposed women. CONCLUSIONS: For exposure levels within standard
      recommended guidelines, radioisotopes are far more likely to play a role in the
      occurrence of spontaneous abortions than X-rays. Such biological effect is not
      detectable by deviations in CA frequency.

PMID- 18058122
TI  - Characterizing the interactions between GPI-anchored alkaline phosphatases and
      membrane domains by AFM.
AB  - In plasma membranes, most glycosylphosphatidylinositol-anchored proteins (GPI
      proteins) would be associated with ordered microdomains enriched in sphingolipids
      and cholesterol. Debates on the composition and the nano- or mesoscales
      organization of these membrane domains are still opened. This complexity of
      biomembranes explains the use, in the recent years, of both model systems and
      atomic force microscopy (AFM) approaches to better characterize GPI
      proteins/membranes interactions. So far, the studies have mainly been focused on
      alkaline phosphatases of intestinal (BIAP) or placental (PLAP) origins
      reconstituted in model systems. The data show that GPI-anchored alkaline
      phosphatases (AP-GPI) molecules inserted in supported membranes can be easily
      imaged by AFM, in physiological buffer. They are generally observed in the most
      ordered domains of model membranes under phase separation, i.e. presenting both
      fluid and ordered domains. This direct access to the membrane structure at a
      mesoscopic scale allows establishing the GPI protein induced changes in
      microdomains size. It provides direct evidence for the temperature-dependent
      distribution of a GPI protein between fluid and ordered membrane domains. Origins
      of reported differences in the behavior of BIAP and PLAP are discussed. Finally,
      advantages and limits of AFM in the study of GPI proteins/membrane domains
      interactions are presented in this review.

PMID- 18058123
TI  - Probing cellular microenvironments and tissue remodeling by atomic force
      microscopy.
AB  - The function of cells is strongly determined by the properties of their
      extracellular microenvironment. Biophysical parameters like environmental
      stiffness and fiber orientation in the surrounding matrix are important
      determinants of cell adhesion and migration. Processes like tissue maintenance,
      wound repair, cancer cell invasion, and morphogenesis depend critically on the
      ability of cells to actively sense and remodel their surroundings. Pericellular
      proteolytic activity and adaptation of migration tactics to the environment are
      strategies to achieve this aim. Little is known about the distinct regulatory
      mechanisms that are involved in these processes. The system's critical
      biophysical and biochemical determinants are well accessible by atomic force
      microscopy (AFM), a unique tool for functional, nanoscale probing and
      morphometric, high-resolution imaging of processes in live cells. This review
      highlights common principles of tissue remodeling and focuses on application
      examples of different AFM techniques, for example elasticity mapping, the
      combination of AFM and fluorescence microscopy, the morphometric imaging of
      proteolytic activity, and force spectroscopy applications of single molecules or
      individual cells. To achieve a more complete understanding of the processes
      underlying the interaction of cells with their environments, the combination of
      AFM force spectroscopy experiments will be essential.

PMID- 18058124
TI  - Inhibition of suicidal erythrocyte death by nitric oxide.
AB  - Nitric oxide (NO) is known to counteract apoptosis by S-nitrosylation of protein
      thiol groups. NO is generated and stored in erythrocytes, which may undergo
      eryptosis, a suicidal cell death similar to apoptosis of nucleated cells.
      Eryptosis is triggered by increased cytosolic Ca2+ activity and/or ceramide and
      characterized by cell shrinkage and phosphatidylserine exposure at the cell
      surface. The present study explored whether nitric oxide could interfere with the
      machinery underlying eryptosis. To this end, erythrocyte phosphatidylserine
      exposure (annexin V-binding) and cell volume (forward scatter) were determined by
      flow cytometry. The Ca2+ ionophore ionomycin (0.1 microM) increased cytosolic
      Ca2+ activity, triggered annexin binding, and decreased forward scatter. The
      annexin binding and decrease of forward scatter but not the increase of cytosolic
      Ca2+ activity were reversed by the NO-donor nitroprusside (1 microM) and
      papanonoate (100 microM). Higher concentrations of nitroprusside (0.1 and 1 mM)
      stimulated eryptosis. Glucose depletion, exposure to C6-ceramide (3 microM),
      hypertonic (addition of 550 mM sucrose), and isotonic (replacement of Cl- with
      gluconate) cell shrinkage all triggered annexin V binding, effects all reversed
      by nitroprusside (1 microM). Dibutyryl-cGMP (1 mM) blunted the ionomycin- but not
      the ceramide-induced annexin V binding. Ionomycin decreased protein nitrosylation
      and thioredoxin activity, effects reversed by the NO-donor papanonoate. Clearance
      of erythrocytes from circulating blood was significantly faster in eNOS knockout
      mice than in their wild-type littermates. In conclusion, nitric oxide
      participates in the regulation of erythrocyte survival, an effect partially
      mimicked by cGMP and paralleled by alterations of protein nitrosylation and
      thioredoxin activity.

PMID- 18058126
TI  - Application of AFM in understanding biomineral formation in diatoms.
AB  - We review previous work and present new data on the application of atomic force
      microscopy (AFM) to study biomineral formation in diatoms, unicellular algae that
      make cell walls of silica. Previous studies examined a small subset of mostly
      larger diatom species, identifying a prevalence of large particulate silica on
      the nanoscale. We survey different structures including valves, girdle bands, and
      elongated spines called setae, in a variety of species, and show a diversity of
      nano- and meso-scale silica morphologies, even on different portions of the same
      structure. A general trend of highly organized mesoscale silica structure on the
      proximal face of cell wall components was observed, with less organized structure
      occurring on the distal face. The highly organized structures have features
      suggestive of an underlying linear template, which defines the area of initial
      silica polymerization. Such features have not been imaged with such clarity
      previously, demonstrating the advantages of AFM to image small differences in
      surface morphology and providing new insights and confirming evidence for models
      of diatom silica structure formation. In addition to its imaging capability, more
      developed application of AFM to map locations of organic template components on
      the nanoscale will greatly aid in elucidating mechanisms of diatom biosilica
      synthesis.

PMID- 18058125
TI  - Pulling single molecules of titin by AFM--recent advances and physiological
      implications.
AB  - Perturbation of a protein away from its native state by mechanical stress is a
      physiological process immanent to many cells. The mechanical stability and
      conformational diversity of proteins under force therefore are important
      parameters in nature. Molecular-level investigations of "mechanical proteins"
      have enjoyed major breakthroughs over the last decade, a development to which
      atomic force microscopy (AFM) force spectroscopy has been instrumental. The giant
      muscle protein titin continues to be a paradigm model in this field. In this
      paper, we review how single-molecule mechanical measurements of titin using AFM
      have served to elucidate key aspects of protein unfolding-refolding and
      mechanisms by which biomolecular elasticity is attained. We outline recent work
      combining protein engineering and AFM force spectroscopy to establish the
      mechanical behavior of titin domains using molecular "fingerprinting."
      Furthermore, we summarize AFM force-extension data demonstrating different
      mechanical stabilities of distinct molecular-spring elements in titin, compare
      AFM force-extension to novel force-ramp/force-clamp studies, and elaborate on
      exciting new results showing that AFM force clamp captures the unfolding and
      refolding trajectory of single mechanical proteins. Along the way, we discuss the
      physiological implications of the findings, not least with respect to muscle
      mechanics. These studies help us understand how proteins respond to forces in
      cells and how mechanosensing and mechanosignaling events may proceed in vivo.

PMID- 18058127
TI  - Increased pathogenesis and inflammation of airways from respiratory syncytial
      virus infection in T cell deficient nude mice.
AB  - Respiratory syncytial virus (RSV) infection is ubiquitous and leads to various
      outcomes between immunocompetent and immunocompromised individuals. This study
      aimed to compare RSV infection and inflammatory responses between immunocompetent
      BALB/c mice and immunodeficient nude mice. RSV titers in both infected BALB/c
      mice and nude mice peaked on the third day post-inoculation, but the nude mice
      had longer lasting and higher levels of viral replication. RSV infection induced
      a more severe grade of pulmonary histopathology and larger numbers of leukocytes
      in airways of nude mice than that of BALB/c mice. RSV infection increased
      pulmonary macrophages and natural killer (NK) cells in both strains of mice.
      Furthermore, infected nude mice had larger numbers of pulmonary macrophages and
      NK cells than infected BALB/c mice. Whereas the RSV infected BALB/c mice secreted
      more tumor necrosis factor -alpha (TNF-alpha), interleukin-12 (IL-12), interferon
      gamma (IFN-gamma) and IL-10 than control BALB/c mice, the infected nude mice had
      higher levels of TNF-alpha, IL-12 and IL-10 than the infected BALB/c mice. The
      inflammation induced by RSV infection did not correspond with the immune response
      of T cells. Macrophages and NK cells were potent immunocytes and inflammatory
      cells in RSV infection especially when T lymphocytes were deficient. Therefore,
      nude mice may be a good model for severe and persistent RSV infection in
      immunocompromised hosts.

PMID- 18058128
TI  - Larvicidal effects of various Euro-Asiatic plants against Culex quinquefasciatus
      Say larvae (Diptera: Culicidae).
AB  - Extracts from 56 species of plants in the Euro-Asiatic region were tested for
      larvicidal activity against the fourth larval instar of the mosquito Culex
      quinquefasciatus Say (Diptera: Culicidae). All plant extracts showed larvicidal
      activity after 24 h of exposure to the plant extracts in a maximal dose of 500
      ppm. The extracts of the plants Otanthus maritimus and Ammi visnaga displayed the
      highest larvicidal effect (LD(50) 7 and 9 ppm, respectively) followed by Acer
      pseudoplatanus, Humulus japonicus, Acer platanoides, Satureja hortensis, Ocimum
      basilicum and Thymus vulgaris (LD(50) 23, 25, 28, 28, 32 and 48 ppm
      respectively). For eight species, the appraisal value of LD(50) was between 51
      and 100 ppm, another eight species from 101 to 200 ppm, 15 species from 201 to
      500 ppm and for 17 species, low mortality showed no lethal dose (LD(50)>500 ppm).

PMID- 18058130
TI  - New records of endoparasites infecting Hypsiboas albopunctatus (Anura: Hylidae)
      in a savanna area in Brasilia, Brazil.
AB  - Seventy specimens of Hypsiboas albopunctatus (Anura: Hylidae) were collected and
      surveyed for endoparasites in Brasilia, Brazil at the end of the rainy season
      (February and March) in 2005. Sixteen males (22.86%) were infected by Rhabdias
      sp., Aplectana sp., Cosmocerca sp., and Falcaustra mascula. Rhabdias sp., a lung
      parasite, presented the highest prevalence (8.57%), mean intensity of infestation
      (1.333), and mean abundance (0.114). Moreover, this is the first report of a
      rhabdiasid nematode in the Hylidae in Brazil. The intestinal parasites,
      Cosmocerca sp. and Aplectana sp., had a similar prevalence (5.71%), but the
      former presented a higher mean intensity of infestation and mean abundance. The
      behavior and food habits of amphibians are responsible for the differences in
      their helminthofauna, and this study presents four new records of nematodes in H.
      albopunctatus.

PMID- 18058129
TI  - Transcriptome profile of Trypanosoma cruzi-infected cells: simultaneous up- and
      down-regulation of proliferation inhibitors and promoters.
AB  - As Trypanosoma cruzi, the etiological agent of Chagas disease, multiplies in the
      cytoplasm of nucleated host cells, infection with this parasite is highly likely
      to affect host cells. We performed an exhaustive transcriptome analysis of T.
      cruzi-infected HeLa cells using an oligonucleotide microarray containing probes
      for greater than 47,000 human gene transcripts. In comparison with uninfected
      cells, those infected with T. cruzi showed greater than threefold up-regulation
      of 41 genes and greater than threefold down-regulation of 23 genes. Real-time
      reverse transcriptase-polymerase chain reaction (RT-PCR) of selected,
      differentially expressed genes confirmed the microarray data. Many of these up-
      and down-regulated genes were related to cellular proliferation, including seven
      up-regulated genes encoding proliferation inhibitors and three down-regulated
      genes encoding proliferation promoters, strongly suggesting that T. cruzi
      infection inhibits host cell proliferation, which may allow more time for T.
      cruzi to replicate and produce its intracellular nests. These findings provide
      new insight into the molecular mechanisms by which intracellular T. cruzi
      infection influences the host cell, leading to pathogenicity.

PMID- 18058131
TI  - The presence of Mycoplasma hominis in isolates of Trichomonas vaginalis impacts
      significantly on DNA fingerprinting results.
AB  - The genetic characterization of Trichomonas vaginalis (Protista:
      Trichomonadidae), the causative agent of trichomoniasis in humans, is central to
      understanding the epidemiology, treatment, drug resistance, and virulence as well
      as the diagnosis and control of this parasite. Various molecular approaches,
      including DNA fingerprinting, have been employed for this purpose, and random
      amplification of polymorphic DNA (RAPD) continues to be utilized. However, little
      attention has been paid to the fact that some T. vaginalis populations can harbor
      symbiotic Mycoplasma hominis and/or other agents, which could cause artifacts in
      the RAPD results. In the present study, we demonstrate clearly that the presence
      of M. hominis from T. vaginalis isolates impacts significantly on RAPD results
      and on the subsequent analyses and interpretation of data sets. Moreover,
      symbiotic M. hominis displays an isolate-to-isolate variability in RAPD profile
      before elimination, suggesting a variability of M. hominis infection.

PMID- 18058132
TI  - A stochastic model of Echinococcus multilocularis transmission in Hokkaido,
      Japan, focusing on the infection process.
AB  - Echinococcus multilocularis causes human alveolar echinococcus. In Japan, high
      prevalence of E. multilocularis among the fox population has been reported
      throughout Hokkaido. Accordingly, control measures, such as fox hunting and the
      distribution of bait containing Praziquantel, have been conducted. This study
      developed a transmission model for individuals in the fox population and included
      a stochastic infection process to assess the prevalence of E. multilocularis. To
      make our model realistic, we used the worm burden for each individual in the fox
      population. We assumed that the worm burden depends on the number of
      protoscoleces in a predated vole and the number of infection experiences. We
      carried out stochastic simulations with 1,000 trials for the situations of
      Koshimizu and Sapporo, Hokkaido, Japan. The distribution of the worm burden among
      foxes obtained using the model agreed with dissection data. The simulation
      indicates that a careful choice of season is necessary for an effective
      distribution of Praziquantel-containing bait. A stochastic model for E.
      multilocularis, which can assess the range of the prevalence in the fox
      population, would be helpful in analyzing their complex life-cycle and also in
      designing control strategies.

PMID- 18058133
TI  - Identification and enzymatic activities of four protein disulfide isomerase (PDI)
      isoforms of Leishmania amazonensis.
AB  - Leishmania parasites primarily infect cells of macrophage lineage and can cause
      leishmaniasis in the skin, mucosal, and visceral organs, depending on both host-
      and parasite-derived factors. The protein disulfide isomerases (PDIs) are thiol
      disulfide oxidoreductases that catalyze the formation, reduction, and
      isomerization of disulfide bonds of proteins in cells. Although four Leishmania
      PDI genes are functionally inferred from homology in the genome sequences, only
      two of them have been expressed as active proteins to date. The functional
      relationship among various PDI enzymes remains largely unclear. In this study, we
      expressed and partially characterized all four L. amazonensis PDIs encoding 52-,
      47-, 40-, and 15-kDa proteins. Homology analysis showed that the sequence
      identity between L. amazonensis (New World) PDIs and their counterpart PDI
      sequences from L. major (Old World) ranged from 76% to 99%. Kinetic
      characterization indicated that while the 15-, 40-, and 47- kDa PDI proteins
      displayed both insulin isomerase and reductase activities, the 52-kDa protein had
      only isomerase activity with no detectable reductase activity. All four PDI
      proteins were recognized by sera from L. amazonensis-infected mice and were
      sensitive to inhibition by standard PDI inhibitors. This study describes the
      enzymatic activities of recombinant L. amazonensis PDIs and suggests a role for
      these proteins in parasite development.

PMID- 18058134
TI  - Apoptosis-related gene expression in hamster opisthorchiasis post praziquantel
      treatment.
AB  - The aim of this study was to investigate the apoptosis-related gene expression in
      hamster opisthorchiasis after praziquantel treatment. Hamsters were infected with
      Opisthorchis viverrini metacercariae then treated with praziquantel. The
      expression of apoptosis-related genes [i.e., apoptosis gene Bcl-2-associated
      protein X (BAX), caspase 9, p53, and protein kinase B (PKB)] was detected by real
      time reverse transcription polymerase chain reaction. Histopathological analyses
      of liver tissues were studies by staining the sections with hematoxylin and eosin
      using light microscopy. Apoptotic assay was used to localize the apoptotic cell
      death. The results show that BAX, Akt/PKB, p53, and caspase 9 expression level
      were significantly increased on day 30 post infection and at 6 h post treatment
      and gradually decreased nearly to the uninfected control and 24 h post treatment,
      perhaps due to a decrease in inflammatory cells. Apoptotic staining was positive
      reaction at inflammatory cells and nuclei of epithelial bile ducts. Although
      using praziquantel has an advantage in killing parasites, our results show the
      effect of praziquantel treatment from host immune response that induces increased
      apoptosis-related genes in the short term due to an increase in inflammatory
      cells surrounding the bile ducts.

PMID- 18058135
TI  - Stem cells: established facts, open issues, and future directions.

PMID- 18058136
TI  - Eye involvement in children with primary focal segmental glomerulosclerosis.
AB  - Distinct eye abnormalities have been described in children with nephrotic
      syndrome, particularly in diffuse mesangial sclerosis (i.e. Pierson syndrome).
      The aim of the study was to investigate whether there were any associated ocular
      anomalies in children with steroid-resistant nephrotic syndrome (SRNS), all of
      whom had revealed primary focal segmental glomerulosclerosis in biopsy. Thirty
      three SRNS patients (16 male, 17 female) with a median age of 10.5 years (range 3
      25 years) were enrolled in the study. Twenty steroid-sensitive nephrotic syndrome
      (SSNS) patients (ten male, ten female) with a median age of 8 years (range 3-15
      years) served as controls. All SRNS patients were examined by mutational analysis
      for mutations in the NPHS2, WT1, and LAMB2 genes. Nine out of 33 SRNS patients
      (27.2%) showed various eye abnormalities. However, no abnormal ocular findings
      were detected in any of the SSNS patients. Abnormal eye findings detected in SRNS
      patients were anisometropic amblyopia (n = 4), Mittendorf's dots (n = 4), myopic
      astigmatism (n = 3) and exotropia (n = 1). Macular pigment changes (n = 1),
      posterior subcapsular opacities (n = 1) and cataract (n = 1) were considered as
      steroid-induced side effects. In four patients, more than one eye abnormality was
      found. Mutational analysis for the NPHS2, WT1 and LAMB2 genes revealed disease
      causing mutations in 24.2% of patients. Homozygous NPHS2 mutations were detected
      in five patients (15.1%), all of whom had parental consanguinity. In three
      patients (9%) from non-consanguineous parents, heterozygous de novo WT1 mutations
      were detected as disease-causing mutations. No LAMB2 mutation was detected in any
      patient. While four out of five (80%) patients with homozygous NPHS2 mutations
      showed at least one abnormal ocular finding (i.e. Mittendorf's dot or anisometric
      amblyopia), none of the patients with a WT1 mutation had ocular involvement. In
      conclusion, ocular involvement may accompany SRNS caused by primary focal
      segmental glomerulosclerosis (FSGS). Ophthalmologic evaluation at the time of
      diagnosis might be beneficial to characterize further the spectrum of this
      possible association.

PMID- 18058137
TI  - Automated peritoneal dialysis as the modality of choice: a single-center, 3-year
      experience with 458 children in Mexico.
AB  - Automated peritoneal dialysis (APD) has been considered as the ideal dialysis
      modality for pediatric patients. This study reports the 3-year APD experience
      with 458 end-stage renal disease (ESRD) children who started APD in a single
      pediatric center in Mexico City between June 2003 and June 2006. By June 2003,
      there were 310 patients being treated with continuous ambulatory peritoneal
      dialysis (CAPD). At that time, these patients were gradually switched to APD,
      with priority being given to those prescribed more than four exchanges per day,
      younger than 6 years of age, or presenting complications [hernias or decreased
      ultrafiltration (UF)]. An improvement of daily UF was observed when the patients
      were switched from CAPD (590 +/- 340 ml/day) to APD (846 +/- 335 ml/day). The
      presence of edema decreased (from 67% to 8%) as well as the percentage of
      patients requiring antihypertensive drugs (from 83% to 38%), the peritonitis rate
      improved from one episode every 35 patient/month to one episode every 47
      patient/month, the total number of hospitalizations decreased (from 384 to 51),
      and 85% of children attended school. While waiting for renal transplant, APD is
      the dialysis modality of choice for ESRD children at the La Raza Medical Center
      in Mexico City.

PMID- 18058138
TI  - A simple heat alert system for Melbourne, Australia.
AB  - A simple heat alert system, based solely on predicted maximum and minimum daily
      temperatures, has been developed for the city of Melbourne in southeast
      Australia. The system is based upon a demonstration that, when mean daily
      temperature exceeds a threshold of 30 degrees C (mean of today's maximum
      temperature and tonight's minimum temperature), the average daily mortality of
      people aged 65 years or more is about 15-17% greater than usual. Similar numbers
      of excess deaths also occur when daily minimum temperatures exceed 24 degrees C
      (increases of 19-21% over expected death rate), so a heat alert system based
      solely on this widely available weather forecast variable is also feasible. No
      strong signal of excess heat-related deaths appears when the data are stratified
      using daily maximum temperatures. This may be because in Melbourne some days with
      very high maximum temperatures will be affected by the passage of cool changes
      and cold fronts in the afternoon, leading to a rapid drop in temperature (i.e.,
      some days with high maximum temperatures will not continue to be hot throughout
      the day and into the evening). A single day with temperatures exceeding the
      thresholds noted above is sufficient to cause this increase in mortality, rather
      than requiring an extended heat wave. The increased daily mortality does not
      appear to represent a short-term advancement of mortality.

PMID- 18058139
TI  - EPR and ENDOR studies of Fe(II) hemoproteins reduced and oxidized at 77 K.
AB  - gamma-irradiation of frozen solutions of Fe(II) hemoproteins at 77 K generates
      both electron paramagnetic resonance (EPR) active singly reduced and oxidized
      heme centers trapped in the conformation of the Fe(II) precursors. The reduction
      products of pentacoordinate (S = 2) Fe(II) globins, peroxidases and cytochrome
      P450cam show EPR and electron-nuclear double resonance (ENDOR) spectra
      characteristic of (3d 7) Fe(I) species. In addition, cryoreduced Fe(II) alpha
      chains of hemoglobin and myoglobin exhibit an S = 3/2 spin state produced by
      antiferromagnetic coupling between a porphyrin anion radical and pentacoordinate
      (S = 2) Fe(II). The spectra of cryoreduced forms of Fe(II) hemoglobin alpha
      chains and deoxymyoglobin reveal that the Fe(II) precursors adopt multiple
      conformational substates. Reduction of hexacoordinate Fe(II) cytochrome c and
      cytochrome b5 as well as carboxy complexes of deoxyglobins produces only Fe(II)
      porphyrin pi-anion radical species. The low-valent hemoprotein intermediates
      produced by cryoreduction convert to the Fe(II) states at T > 200 K.
      Cryogenerated Fe(III) cytochrome c and cytochrome b5 have spectra similar to
      these for the resting Fe(III) states, whereas the spectra of the products of
      cryooxidation of pentacoordinate Fe(II) globins and peroxidases are different.
      Cryooxidation of CO-Fe(II) globins generates Fe(III) hemes with quantum
      mechanically admixed S = 3/2, 5/2 ground states. The trapped Fe(III) species
      relax to the equilibrium ferric states upon annealing at T > 190 K. Both
      cryooxidized and reduced centers provide very sensitive EPR/ENDOR structure
      probes of the EPR-silent Fe(II) state.

PMID- 18058140
TI  - Cisplatin and siRNA interference with structure and function of Wnt-5a mRNA:
      design and in vitro evaluation of targeting AU-rich elements in the 3' UTR.
AB  - Wnt-5a is a secreted glycoprotein which has been shown to be involved in the
      regulation of cell adhesion and motility, processes which are of importance in
      metastasis formation by cancer cells. We here present an initial study aiming at
      evaluating whether small interfering RNA (siRNA) in combination with cisplatin
      can be used to modulate protein expression levels under in vitro conditions. For
      this purpose, an AU-rich region corresponding to the initial 260 bases of the Wnt
      5a 3' untranslated region was chosen as the target. The effect of four different
      siRNAs was evaluated by analysis of protein suppression levels in rabbit
      reticulocyte lysate (RRL) and an immortalized noncancerous mammary epithelial
      (HB2) cell line by monitoring the activity of transiently expressed luciferase.
      The specificity and kinetics for hybridization of the siRNA with the messenger
      RNA target were followed by digestion techniques and analysis by polyacrylamide
      gel electrophoresis. Specific and temperature-dependent hybridization was
      observed, with a half-life of approximately 0.5 h at 4 degrees C. Significant
      downregulation of luciferase activity was obtained in the micromolar and
      nanomolar range, for RRL and HB2, respectively. In addition, the downregulation
      of protein production caused by addition of cisplatin could be further
      potentiated by addition of siRNA in a selective manner. The latter observation
      suggests that combined use of cisplatin and siRNA could be a method to decrease
      therapeutically used cisplatin concentrations. Thus, toxic side effects could be
      minimized while key proteins are targeted in a highly specific manner.

PMID- 18058141
TI  - Effects on spectrum and susceptibility patterns of isolates causing bloodstream
      infection by restriction of fluoroquinolone prophylaxis in a hematology-oncology
      unit.
AB  - The emergence of fluoroquinolone-resistant gram-negative organisms has been
      demonstrated in patients given fluoroquinolone prophylaxis. To prevent increases
      in resistant bacteria, we restricted prophylactic use of fluoroquinolones. The
      spectrum and susceptibility patterns of isolates causing bloodstream infection
      (BSI) were assessed in patients receiving chemotherapy during periods of routine
      prophylaxis (period A: October 2001 to May 2003) and restricted prophylaxis
      (period B: June 2003 to January 2005). The total number of patients receiving
      chemotherapy was 442 during period A and 365 during period B. No significant
      differences were seen between periods with respect to patient characteristics.
      BSI was identified in 42 patients (44 episodes) during period A and 69 patients
      (74 episodes) during period B. Incidence of BSI increased significantly from
      10.0% (44/442) during period A to 20.3% (74/365) during period B (P < 0.0001).
      Rate of Enterobacteriaceae BSI increased significantly, from 2.0% (9/442) during
      period A to 8.2% (30/365) during period B (P < 0.0001). For all BSI episodes, the
      proportion of BSI with gram-positive cocci decreased from 63.6% (28/44) during
      period A to 44.6% (33/74) during period B (P = 0.045), while the proportion of
      BSI with Enterobacteriaceae increased from 20.5% (9/44) to 40.5% (30/74) (P <
      0.0001). The proportion of fluoroquinolone-resistant Enterobacteriaceae BSI for
      all Enterobacteriaceae BSI decreased from 75% (9/12) during period A to 17%
      (5/30) during period B (P = 0.0078). Restriction of fluoroquinolone prophylaxis
      affects the etiology of BSI and reduces the proportion of drug-resistant
      organisms.

PMID- 18058142
TI  - Health insurance theory: the case of the missing welfare gain.
AB  - An important source of value is missing from the conventional welfare analysis of
      moral hazard, namely, the effect of income transfers (from those who purchase
      insurance and remain healthy to those who become ill) on purchases of medical
      care. Income transfers are contained within the price reduction that is
      associated with standard health insurance. However, in contrast to the income
      effects contained within an exogenous price decrease, these income transfers act
      to shift out the demand for medical care. As a result, the consumer's willingness
      to pay for medical care increases and the resulting additional consumption is
      welfare increasing.

PMID- 18058143
TI  - Evolving mechanical properties of a model of abdominal aortic aneurysm.
AB  - The novel three-dimensional (3D) mathematical model for the development of
      abdominal aortic aneurysm (AAA) of Watton et al. Biomech Model Mechanobiol 3(2):
      98-113, (2004) describes how changes in the micro-structure of the arterial wall
      lead to the development of AAA, during which collagen remodels to compensate for
      loss of elastin. In this paper, we examine the influence of several of the
      model's material and remodelling parameters on growth rates of the AAA and
      compare with clinical data. Furthermore, we calculate the dynamic properties of
      the AAA at different stages in its development and examine the evolution of
      clinically measurable mechanical properties. The model predicts that the maximum
      diameter of the aneurysm increases exponentially and that the ratio of systolic
      to diastolic diameter decreases from 1.13 to 1.02 as the aneurysm develops; these
      predictions are consistent with physiological observations of Vardulaki et al. Br
      J Surg 85:1674-1680 (1998) and Lanne et al. Eur J Vasc Surg 6:178-184 (1992),
      respectively. We conclude that mathematical models of aneurysm growth have the
      potential to be useful, noninvasive diagnostic tools and thus merit further
      development.

PMID- 18058144
TI  - Stress field in actin gel growing on spherical substrate.
AB  - Polymerization of actin to form an elastic gel is one of the main mechanisms
      responsible for cellular motility. The particular problem addressed here stems
      from the need to model theoretically the growth of actin gel under controlled
      conditions, as observed in experiments. A biomimetic in vitro system which
      consists of a spherical latex bead, coated by the enzymatic protein ActA, and a
      reconstituted cytoplasm within which such beads are placed, induces
      polymerization of actin on the surface of the bead in the form of successive
      elastic thin spherical layers. Each newly formed layer pushes outward, and is
      pushed inward by, the already formed spherical layers which altogether constitute
      an elastic spherical shell of thickness h varying with time. Thus, a stress field
      is created in the shell which in turn affects the rate of polymerization as well
      as that of dissociation of actin gel. Given this bio-chemo-mechanical coupling,
      the accurate determination of the stress field becomes a subject of great
      importance for the understanding of the process, and it is the main objective of
      this work. The problem is addressed by first assuming appropriate constitutive
      laws for the actin gel elastic material, and then solving the only non-trivial
      stress equilibrium differential equation along the radial direction assuming
      spherical symmetry. A linear and a non-linear constitutive model for isotropic
      elasticity is used, appropriate for small and finite strains, respectively, and
      the solution is found in closed analytical forms in both cases. Two important
      conclusions are reached. First, the stress field depends strongly on the
      compressibility of the actin gel medium via the value of the Poisson ratio, for
      both linear and non-linear analysis. Second, the linear and non-linear solutions
      are very close for small strains, but they diverge progressively as the strains
      increase from small to large. Guided by available experimental data on the
      observed strain levels, the analytical results are illustrated by selected graphs
      of stress variation along the radial direction. At the end some comments and
      suggestions on the bio-chemo-mechanical coupling of actin gel growth and
      resorption are presented, where the role of properly defined joint isotropic
      invariants of stress and a unit vector along the predominant direction of free
      ends of actin filaments at the polymerization site is introduced.

PMID- 18058145
TI  - Hermann Buhl's special achievements : The 2nd International Symposium on Hypoxia
      in Training and Rehabilitation 2007 in honor of the Austrian/Bavarian
      mountaineer.

PMID- 18058146
TI  - Evidence for myxobacterial origin of eukaryotic defensins.
AB  - Antimicrobial defensins with the cysteine-stabilized alpha-helical and beta-sheet
      (CS alpha beta) motif are a large family of ancient, evolutionarily related
      innate immunity effectors of multicellular organisms. Although the widespread
      distribution in plants, fungi, and invertebrates suggests their uniqueness to
      Eukarya, it is unknown whether these eukaryotic defensins originated before or
      posterior to the emergence of eukaryotes. In this study, we provide evidence in
      support of the existence of defensin-like peptides (DLPs) in myxobacteria based
      on structural bioinformatics analysis, which recognized two bacterial peptides
      with a conserved cysteine-stabilized alpha-helical motif, a nested structural
      unit of the CS alpha beta motif. Similarity in sequence and structure to fungal
      DLPs together with restricted distribution to the myxobacteria as well as central
      role of the myxobacteria in the origin of eukaryotes suggest that the bacterial
      DLPs represent the ancestor of the eukaryotic defensins and could mediate immune
      defense of early eukaryotes after gene transfer to the proto-eukaryotic genome.
      Our work thus offers a basis for further investigation of prokaryotic origin of
      eukaryotic immune effector molecules.

PMID- 18058147
TI  - [Rare diseases as models in clinical research--from genetics to better medical
      care ].

PMID- 18058149
TI  - [Disorders of sex development].
AB  - Disorders of sex development (DSD) include a heterogeneous group of heritable
      disorders of sex determination and differentiation, formerly termed
      "intersexuality". This includes chromosomal as well as monogenic disorders, which
      inhibit or change primarily genetic or endocrine pathways of normal sex
      development. However, in most patients affected, no definitive cause for the
      disorder can be found. Therefore, the birth of a child with ambiguous genitalia
      still represents an enormous challenge. For the structuring of diagnostic
      procedures, for decision making and also for therapeutic interventions a highly
      specialized team of physicians of different subspecialties and of experts for
      psychosocial care is needed to counsel parents and patients accordingly. This
      manuscript shall explain the genetic and molecular origins of DSD, the new DSD
      nomenclature, the consecutive classification and steps for diagnosis. New
      scientific topics on DSD are presented.

PMID- 18058148
TI  - [Hereditary movement disorders].
AB  - Hereditary movement disorders comprise a group of genetically defined diseases
      characterized by an impaired control of movements, ataxia and/or spasticity.
      Affected individuals are disabled, their quality of life significantly reduced
      and their life expectancy shortened. One or more genetic causes have been
      identified for many of these diseases, including Huntington's disease, Wilson's
      disease, spinocerebellar ataxias, recessive ataxias, hereditary spastic
      paraplegia and hereditary dystonias. Due to their characteristic molecular and
      biochemical pathogenesis, these rare diseases can often serve as models for more
      common disorders such as Alzheimer's disease or Parkinson's disease. The primary
      tasks of the German Network of Hereditary Movement Disorders (GeNeMove), funded
      by the German Ministry for Education and Research (BMBF), are to co-ordinate
      basic scientific research and clinical research into rare hereditary movement
      disorders and to improve the cooperation between the German centers specializing
      in hereditary movement disorders. For each of the diseases in its scope, GeNeMove
      works at creating standardized documentation of symptoms and the disease's
      progressive course over time; developing rating scales for clinical examinations
      and guidelines for therapy; improving genetic testing; fostering genetic
      research; and collecting samples of DNA, tissue, CSF and blood from sufferers of
      the disease for biobanks.

PMID- 18058156
TI  - The FTO gene, implicated in human obesity, is found only in vertebrates and
      marine algae.
AB  - Human obesity is a main cause of morbidity and mortality. Recently, several
      studies have demonstrated an association between the FTO gene locus and early
      onset and severe obesity. To date, the FTO gene has only been discovered in
      vertebrates. We identified FTO homologs in the complete genome sequences of
      various evolutionary diverse marine eukaryotic algae, ranging from unicellular
      photosynthetic picoplankton to a multicellular seaweed. However, FTO homologs
      appear to be absent from all other completely sequenced genomes of plants, fungi,
      and invertebrate animals. Although the biological roles of these marine algal FTO
      homologs are still unknown, these genes will be useful for exploring basic
      protein features and could hence help unravel the function of the FTO gene in
      vertebrates and its inferred link with obesity in humans.

PMID- 18058158
TI  - Availability and bioaccessibility of metals in fine particles of some urban
      soils.
AB  - Metals in urban soils might be transferred to humans via ingestion, dermal
      contact, or breathing, especially to children due to the "hand to mouth" activity
      during outdoor activities in playground and recreational areas. This involuntary
      soil ingestion depends on soil adherence to skin; it is known that the adhesion
      process tends to exclude particles greater than 50 microm, so the fraction below
      this diameter would be the most dangerous for health. The aim of this work was to
      study the "availability", estimated by the EDTA extraction, and "oral
      bioaccessibility", estimated by the Simple Bioaccessibility Extraction Test
      (SBET), of several metals in urban soils of two European cities (Sevilla and
      Torino), as related to the soil particle size distribution. Torino and Sevilla
      showed different levels of metal contents, availability, and bioaccessibility. In
      Torino, the finer particles showed metal enrichment of Cu, Zn, and, to a lesser
      extent, Pb, whereas in Sevilla, all of the studied metals showed this enrichment
      compared to the whole soils. The whole soil cannot be used as a good general
      indicator of the bioaccessibility of metals in the finest fractions of the soil.
      Metal availability was higher in the clay fraction (<2 microm) than in other
      fractions or whole soils in both cities, and principal component analysis shows
      that availability is especially due to this fraction. In contrast, Cu and Pb
      bioaccessibility in the clay fraction seems to be slightly lower than, or
      comparable to, all of the other fractions and the whole soil. Bioaccessibility of
      Cr and Ni is clearly greater in the coarser fractions of Sevilla than those of
      Torino, despite the considerably greater total contents of both metals in the
      latter city. Adsorbed metal forms are assumed to be preferentially responsible
      for metals released by EDTA. A different origin is attributed to bioaccessible
      metal forms. Anthropic influence seems more important in determining metal
      availability and bioaccessibility in urban soils of both cities than the
      different geological or industrial characteristics.

PMID- 18058159
TI  - Cardiac arrest secondary to long QT(C )in a child with propionic acidemia.
AB  - In 2006 a case report was published in this journal of a child with known
      propionic acidemia being diagnosed with the long QT(C) syndrome. This following
      case documents the first reported case of a child with this condition suffering a
      life-threatening event from the associated long QT(C) syndrome.

PMID- 18058157
TI  - The origin and evolution of tRNA inferred from phylogenetic analysis of
      structure.
AB  - The evolutionary history of the two structural and functional domains of tRNA is
      controversial but harbors the secrets of early translation and the genetic code.
      To explore the origin and evolution of tRNA, we reconstructed phylogenetic trees
      directly from molecular structure. Forty-two structural characters describing the
      geometry of 571 tRNAs and three statistical parameters describing thermodynamic
      and mechanical features of molecules quantitatively were used to derive
      phylogenetic trees of molecules and molecular substructures. Trees of molecules
      failed to group tRNA according to amino acid specificity and did not reveal the
      tripartite nature of life, probably due to loss of phylogenetic signal or because
      tRNA diversification predated organismal diversification. Trees of substructures
      derived from both structural and statistical characters support the origin of
      tRNA in the acceptor arm and the hypothesis that the top half domain composed of
      acceptor and pseudouridine (TPsiC) arms is more ancient than the bottom half
      domain composed of dihydrouridine (DHU) and anticodon arms. This constitutes the
      cornerstone of the genomic tag hypothesis that postulates tRNAs were ancient
      telomeres in the RNA world. The trees of substructures suggest a model for the
      evolution of the major functional and structural components of tRNA. In this
      model, short RNA hairpins with stems homologous to the acceptor arm of present
      day tRNAs were extended with regions homologous to TPsiC and anticodon arms. The
      DHU arm was then incorporated into the resulting three-stemmed structure to form
      a proto-cloverleaf structure. The variable region was the last structural
      addition to the molecular repertoire of evolving tRNA substructures.

PMID- 18058160
TI  - Comparison of the effectiveness of oral sildenafil versus oxygen administration
      as a test for feasibility of operation for patients with secondary pulmonary
      arterial hypertension.
AB  - It is shown that phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil
      can modulate pulmonary arterial hypertension (PAH) via increasing the level of
      guanosine-3,5-cyclic monophosphate (cGMP) and decreases pulmonary artery pressure
      (PAP). In this study we determined the effectiveness of sildenafil and compared
      its efficacy with inhaled nasal oxygen (O2) during cardiac catheterization in
      patients with congenital heart diseases (CHD) and PAH, as a test of feasibility
      for surgical repair of the patients. We studied 15 patients, 9 male and 6 female,
      with a mean age of 8.3 years. Hemodynamic measurements were made at baseline,
      after O2 administration for 20 min (5 L/min by mask), and then 45 min after
      administration of a single dose of sildenafil (0.5 mg/kg orally or via
      nasogastric tube). Mean PAP at baseline was 72.2 +/- 12.54 mm Hg and was reduced
      by sildenafil to 52.5 +/- 9.6 and by O2 to 61.3 +/- 10.39. Both sildenafil and O2
      decreased PAP effectively (p = 0.08 and p = 0.04, respectively). Pulmonary
      vascular resistance (PVR) was calculated for 12 patients, with a baseline level
      of 9.08 +/- 1.09 mm Hg . L(-1) . min, which was significantly decreased by O2, to
      3.74 +/- 0.43, and by sildenafil, to 5.93 +/- 0.75 (p = 0.005 and p = 0.05,
      respectively). Sildenafil, as a single oral dose, can effectively reduce PAP and
      PVR. This novel PDE5 inhibitor can be used for assessment of feasibility of
      operation for patients with CHD and PAH when inhaled NO is not available.

PMID- 18058161
TI  - 62-kb plasmids harboring rulAB homologues confer UV-tolerance and epiphytic
      fitness to Pseudomonas syringae pv. syringae mango isolates.
AB  - The presence of genetic determinants homologous to rulAB genes for ultraviolet
      (UV) radiation resistance was determined in a collection of Pseudomonas syringae
      pv. syringae strains isolated from mango. The potential role of these plasmids in
      UV tolerance and ecological fitness in the mango phyllosphere was also evaluated.
      Nearly all of the 62-kb plasmids present in the P. syringae pv. syringae strains
      hybridized with a rulAB probe, but these 62-kb plasmids showed differences in
      restriction patterns. In vitro assays of tolerance to UV radiation of P. syringae
      pv. syringae strains showed a higher survival of the strains harboring the 62-kb
      plasmids compared to strains lacking plasmids when exposed to UVC or UVA+B
      fractions. Similar results were observed when transconjugants harboring the 62-kb
      plasmid were tested. Survival assays were carried out under field conditions, and
      a higher survival of P. syringae pv. syringae strains harboring 62-kb plasmids
      under direct solar radiation on the adaxial surface of leaves was also observed.
      When the assays were carried out in shady areas or on the abaxial surface of
      leaves, survival time was comparable for all the assayed strains, whether or not
      they contained a 62-kb plasmid hybridizing to rulAB. Our results indicate that P.
      syringae pv. syringae strains harboring 62-kb plasmids show an increase in
      ecological fitness when colonizing the mango phyllosphere.

PMID- 18058163
TI  - The factors considered by editors of plastic surgery journals in evaluating
      submitted manuscripts.
AB  - The publication of clinical- or laboratory-based research in peer-reviewed
      journals is seen as the final end point rewarding many months of detailed work.
      For both trainees and established consultants alike, having a submitted
      manuscript rejected is both frustrating and disheartening. All journals publish
      details regarding manuscript structure and preparation. However these "in-house"
      guidelines tell little about what editors are looking for in their journals, and
      indeed what can be done to ensure acceptance of any work that researchers submit.
      The authors surveyed the editors of 40 peer-reviewed plastic surgery and related
      subspeciality journals regarding factors that influence their decision to accept
      or reject a manuscript. The aim was to establish factors that influence editors'
      decisions regarding submitted papers, which then would enable aspects to be
      highlighted that authors could address to expedite publication and produce
      relevant guidelines to facilitate this process. The results demonstrate that
      editors value an original, rigorously designed manuscript with valid methodology
      and appropriate conclusions. Adherence to the philosophy and aims of the journal
      and the journal's target audience will further improve the likelihood of
      successful publication for the submitting authors.

PMID- 18058162
TI  - Screenhouse and field persistence of nonpathogenic endophytic Fusarium oxysporum
      in Musa tissue culture plants.
AB  - Two major biotic constraints to highland cooking banana (Musa spp., genome group
      AAA-EA) production in Uganda are the banana weevil Cosmopolites sordidus and the
      burrowing nematode Radopholus similis. Endophytic Fusarium oxysporum strains
      inoculated into tissue culture banana plantlets have shown control of the banana
      weevil and the nematode. We conducted screenhouse and field experiments to
      investigate persistence in the roots and rhizome of two endophytic Fusarium
      oxysporum strains, V2w2 and III4w1, inoculated into tissue-culture banana
      plantlets of highland cooking banana cultivars Kibuzi and Nabusa. Re-isolation of
      F. oxysporum showed that endophyte colonization decreased faster from the
      rhizomes than from the roots of inoculated plants, both in the screenhouse and in
      the field. Whereas rhizome colonization by F. oxysporum decreased in the
      screenhouse (4-16 weeks after inoculation), root colonization did not. However,
      in the field (17-33 weeks after inoculation), a decrease was observed in both
      rhizome and root colonization. The results show a better persistence in the roots
      than rhizomes of endophytic F. oxysporum strains V2w2 and III4w1.

PMID- 18058164
TI  - The use of buflomedil in reduction mammaplasty for a previously irradiated
      breast: a case report.
AB  - In recent years, lumpectomy combined with breast irradiation and chemotherapy, as
      a part of conservation therapy for breast cancer, has well-established results.
      Little has been published on reduction mammoplasty for breast-irradiated
      patients. These patients have increased risks of nipple necrosis, wound
      complications, and delayed healing. Breast reduction techniques that rely on
      minimum skin undermining combined with the use of buflomedil may prevent major
      postoperative complications in breast-irradiated patients. Buflomedil was
      administered intraoperatively and for 14 days after the procedure. The use of
      buflomedil in reduction mammaplasty for a previously irradiated breast patient
      has not been heretofore described. The case of a 58-year-old woman who underwent
      bilateral breast reduction after breast conservation therapy is reported.

PMID- 18058165
TI  - Controlled trials in aesthetic plastic surgery: a 16-year analysis.
AB  - Aesthetic surgery is one pillar of plastic surgery. Thus, not surprisingly,
      journals exist that focus predominantly on advances within this subspecialty.
      However, rarely has the process of systematic reviewing that identified
      randomized controlled trials (RCTs) and controlled clinical trials (CCTs) been
      conducted within this subspecialty. All original articles published in Aesthetic
      Plastic Surgery were analyzed to identify all RCTs and CCTs. The proportion of
      RCTs and CCTs in all original articles was determined, and the quality of
      reporting was assessed on the basis of established quality items. Additional
      parameters were investigated including reporting of statistically significant
      differences, type of institution, and country affiliation of the first author. Of
      the 1,048 original articles analyzed, 11 (1%) and 24 (2.3%) articles met the
      inclusion criteria for RCTs and CCTs, respectively. Only two studies were single
      blinded, whereas only one study reported on successful double blinding and
      appropriate allocation concealment. Notably, these trials were RCTs. Participant
      dropout was reported in one study. Statistically significant differences were
      reported in 18 trials, 6 of which were RCTs. The annual publication of RCTs has
      increased over the past 5 years. North America and Europe contributed a total of
      28 controlled trials (80%). Controlled trials are being conducted in aesthetic
      surgery at a strikingly low rate. However, a recent increase in published RCTs
      reflects the recognition that performing outcome studies is pivotal in moving
      practice toward a foundation based on assessment by outcome. The quality of
      reporting, however, needs improvement.

PMID- 18058166
TI  - Numeric expression of aesthetics and beauty.
AB  - Debate over what constitutes beauty, particularly beauty of the human body, has
      raged since philosophy began. Interested scholars have debated the meaning of
      beauty for centuries. However, it seems that numbers and the resulting numeric
      relationships play a fundamental role in the classification of the human body,
      and that a harmonic profile or body shape is produced only at certain definite
      numeric relationships. The beauty of individual features depends on "ideal"
      proportions, and it is suggested that expressing beauty in terms of geometry is
      possible. As the demand for aesthetic surgery has increased tremendously over the
      past few decades, it is becoming essential to be able to assess the possible
      satisfaction that can be expected after an aesthetic surgery procedure and to
      determine the beauty of the final result as precisely as possible.

PMID- 18058167
TI  - How to quantify sustainable development: a risk-based approach to water quality
      management.
AB  - Since the term was coined in the Brundtland report in 1987, the issue of
      sustainable development has been challenged in terms of quantification. Different
      policy options may lend themselves more or less to the underlying principles of
      sustainability, but no analytical tools are available for a more in-depth
      assessment of the degree of sustainability. Overall, there are two major schools
      of thought employing the sustainability concept in managerial decisions: those of
      measuring and those of monitoring. Measurement of relative sustainability is the
      key issue in bridging the gap between theory and practice of sustainability of
      water resources systems. The objective of this study is to develop a practical
      tool for quantifying and assessing the degree of relative sustainability of water
      quality systems based on risk-based indicators, including reliability,
      resilience, and vulnerability. Current work on the Karoun River, the largest
      river in Iran, has included the development of an integrated model consisting of
      two main parts: a water quality simulation subroutine to evaluate Dissolved
      Oxygen Biological Oxygen Demand (DO-BOD) response, and an estimation of risk
      based indicators subroutine via the First Order Reliability Method (FORM) and
      Monte Carlo Simulation (MCS). We also developed a simple waste load allocation
      model via Least Cost and Uniform Treatment approaches in order to consider the
      optimal point of pollutants control costs given a desired reliability value which
      addresses DO in two different targets. The Risk-based approach developed herein,
      particularly via the FORM technique, appears to be an appropriately efficient
      tool for estimating the relative sustainability. Moreover, our results in the
      Karoun system indicate that significant changes in sustainability values are
      possible through dedicating money for treatment and strict pollution controls
      while simultaneously requiring a technical advance along change in current
      attitudes for environment protection.

PMID- 18058168
TI  - Biliary complications after duct-to-duct biliary reconstruction in living-donor
      liver transplantation: causes and treatment.

PMID- 18058169
TI  - Hereditary non-medullary thyroid cancer.
AB  - An estimated 5% of all non-medullary thyroid cancers are hereditary. If three or
      more first-degree relatives are affected, there is a greater than 94% chance that
      these cases are hereditary non-medullary thyroid cancer (HNMTC). Although, the
      susceptibility gene(s) for HNMTC has not been identified, there are enough
      epidemiologic studies and kindreds reported to suggest a hereditary
      predisposition to thyroid cancer. Until the susceptibility genes are identified,
      clinicians will have to rely on comprehensive history taking to identify at-risk
      families and clinically screen at-risk family members. When families are at risk
      for HNMTC, it is unclear whether neck examination and or neck ultrasound is most
      effective for screening. Hereditary non-medullary thyroid cancer is associated
      with more aggressive disease than sporadic HNMTC, especially in index cases, with
      higher rates of multicentric tumors, lymph node metastasis, and extrathyroidal
      invasion. Aggressive screening may benefit other members of the affected kindred
      because the outcome for the non-index cases is better. Although no studies have
      demonstrated any difference in mortality in patients with HNMTC versus sporadic
      disease, disease-free survival is shorter in HNMTC. Aggressive surgical and
      postoperative medical therapy is warranted in patients with HNMTC. It is likely
      that emerging molecular approaches may help identify the gene or genes involved
      in HNMTC which would have important clinical ramifications.

PMID- 18058170
TI  - To the editor: the role of prophylactic surgery in cancer prevention.

PMID- 18058171
TI  - Experimental study on transarterial administration of GRGDSP combined with
      transarterial chemoembolization in rats with hepatic carcinoma.
AB  - PURPOSE: To evaluate the effects of transarterial administration of an integrin
      antagonist, GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro), combined with transarterial
      chemoembolization (TACE) to treat hepatic carcinoma in rats. METHODS: Walker-256
      tumor was implanted beneath the liver capsule in 26 Wistar rats. Animal subjects
      were assigned to groups based on which treatment was injected into the hepatic
      artery: group A, GRGDSP + TACE; group B, TACE alone; and group C, normal saline.
      Magnetic resonance imaging (MRI), tumor pathology, and immunohistochemistry were
      performed to assess each treatment. RESULTS: The ratios of the post-treatment to
      pretreatment tumor volumes (V2/V1) in groups A, B, and C were 4.42 +/- 0.48, 6.98
      +/- 1.09, and 13.00 +/- 1.68, respectively. The metastatic potential of the
      tumors was assessed by tumor cell nest counts, which were 5.00 +/- 1.25, 6.63 +/-
      1.60, and 7.22 +/- 1.92 in groups A, B, and C, respectively. Microvessel density
      (MVD) was quantified by measuring von Willebrand factor density values, which
      were 0.18 +/- 0.02, 0.22 +/- 0.02, and 0.23 +/- 0.02 in groups A, B, and C,
      respectively. CONCLUSIONS: Transarterial infusion of GRGDSP combined with TACE
      noticeably inhibited the growth of hepatic carcinoma and intrahepatic metastases
      in rats.

PMID- 18058172
TI  - Optimization of sterilization of Escherichia coli in milk by surfactin and
      fengycin using a response surface method.
AB  - In this paper, the sensitivity of Escherichia coli to surfactin and fengycin was
      observed, and the optimization of the antimicrobial activity of surfactin and
      fengycin to E. coli in milk by a response surface methodology was studied.
      Results showed that E. coli had high sensitivity to these antibiotics, whose
      minimal inhibitory concentrations were 15.625 microg.mL(-1) and 31.25 microg.mL(
      1), respectively. The optimization result indicated that E. coli could be
      sterilized by 5 orders of magnitude when the temperature was 5.5 degrees C, the
      action time was 15.8 h, and the concentration (surfactin/fengycin weight ratio
      1:1) was 14.63 microg.mL(-1).

PMID- 18058173
TI  - Primary pedunculated giant esophageal liposarcoma: case report.
AB  - Liposarcoma is one of the most common soft tissue sarcomas in adults, but the
      incidence of esophageal liposarcoma is extremely low. To our knowledge there are
      only 18 cases of esophageal liposarcoma reported in the English-language
      literature. Here we report a new case of primary esophageal liposarcoma in a 50
      year-old male patient who complained of aggravating dysphagia with intermittent
      vomiting for 6 months. The tumor was located in the upper esophagus. Polypectomy
      was performed and histologic examination showed a well-differentiated
      liposarcoma. Diagnostic and therapeutic tools are discussed and the results of a
      literature review are discussed.

PMID- 18058174
TI  - Varicoid adenocarcinoma of the esophagus: case report.
AB  - Varicoid swellings resemble a varix, or an enlarged and convoluted vessel.
      Varicoid or superficial spreading carcinoma of the esophagus is a rare condition
      demonstrating an appearance similar to esophageal varices and as such can be
      misdiagnosed. In the majority of cases they tend to be squamous cell carcinomas.
      We present only the second reported case of a patient with varicoid
      adenocarcinoma of the esophagus. In the absence of chronic liver disease, we
      advocate that variceal lesions within the esophagus should be regarded with a
      high index of suspicion for possible varicoid esophageal cancer.

PMID- 18058175
TI  - Clinical utility of the 3-ounce water swallow test.
AB  - The 3-ounce water swallow test is frequently used to screen individuals for
      aspiration risk. Prior research concerning its clinical usefulness, however, is
      confounded by inadequate statistical power due to small sample sizes and varying
      methodologies. Importantly, research has been limited to a few select patient
      populations, thereby limiting the widespread generalizability and applicability
      of the 3-ounce test. The purpose of this study was to investigate the clinical
      utility of the 3-ounce water swallow test for determining aspiration status and
      oral feeding recommendations in a large and heterogeneous patient population.
      Fiberoptic endoscopic evaluation of swallowing (FEES) was performed in
      conjunction with the 3-ounce water swallow test on 3000 participants with a wide
      range of ages and diagnoses. A total of 1151 (38.4%) passed and 1849 (61.6%)
      failed the 3-ounce water swallow test. Sensitivity of the 3-ounce water swallow
      test for predicting aspiration status during FEES = 96.5%, specificity = 48.7%,
      and false positive rate = 51.3%. Sensitivity for identifying individuals who were
      deemed safe for oral intake based on FEES results = 96.4%, specificity = 46.4%,
      and false positive rate = 53.6%. Passing the 3-ounce water swallow test appears
      to be a good predictor of ability to tolerate thin liquids. However, failure
      often does not indicate inability to tolerate thin liquids, i.e., low specificity
      and high false-positive rate. Use of the 3-ounce water swallow test alone to make
      decisions regarding safety of liquid intake results in over-referral and
      unnecessary restriction of liquid intake for nearly 50% of patients tested. In
      addition, because 71% of participants who failed the 3-ounce water swallow test
      were deemed safe for an oral diet, nonsuccess on the 3-ounce water swallow test
      is not indicative of swallowing failure. The clinical utility of the 3-ounce
      water swallow test has been extended to include a wide range of medical and
      surgical diagnostic categories. Importantly, for the first time it has been shown
      that if the 3-ounce water swallow test is passed, diet recommendations can be
      made without further objective dysphagia testing.

PMID- 18058176
TI  - The identification of 2,4-diacetylphloroglucinol as an antifungal metabolite
      produced by cutaneous bacteria of the salamander Plethodon cinereus.
AB  - Beneficial bacteria that live on salamander skins have the ability to inhibit
      pathogenic fungi. Our study aimed to identify the specific chemical agent(s) of
      this process and asked if any of the antifungal compounds known to operate in
      analogous plant-bacteria-fungi systems were present. Crude extracts of bacteria
      isolated from salamander skin were exposed to HPLC, UV-Vis, GC-MS, and HR-MS
      analyses. These investigations show that 2,4-diacetylphloroglucinol is produced
      by the bacteria isolate Lysobacter gummosus (AB161361), which was found on the
      red-backed salamander, Plethodon cinereus. Furthermore, exposure of the amphibian
      fungal pathogen, Batrachochytrium dendrobatidis (isolate JEL 215), to different
      concentrations of 2,4-diacetylphloroglucinol resulted in an IC50 value of 8.73
      microM, comparable to crude extract concentrations. This study is the first to
      show that an epibiotic bacterium on an amphibian species produces a chemical that
      inhibits pathogenic fungi.

PMID- 18058177
TI  - Gene expression of different wheat genotypes during attack by virulent and
      avirulent Hessian fly (Mayetiola destructor) larvae.
AB  - Wheat and its relatives possess a number of resistance (R) genes specific for the
      Hessian fly (HF) [Mayetiola destructor (Say)]. HF populations overcome R gene
      resistance by evolving virulence. Virulent HF larvae manipulate the plant to
      produce a nutritionally enhanced feeding tissue and, probably, also suppress
      plant defense responses. Using two wheat R genes, H9 and H13, and three HF
      strains (biotypes) differing in virulence for H9 and H13, we conducted a genome
      wide transcriptional analysis of gene expression during compatible interactions
      with virulent larvae and incompatible interactions with avirulent larvae. During
      both types of interactions, a large number of genes (>1,000) showed alterations
      in gene expression. Analysis of genes with known functions revealed that major
      targets for differential regulation were genes that encoded defense proteins or
      enzymes involved in the phenylpropanoid, cell wall, and lipid metabolism
      pathways. A combination of the enhancement of antibiosis defense, the evasion of
      nutrient metabolism induction, and the fortification and expansion of the cell
      wall are likely the collective mechanism for host-plant resistance observed
      during incompatible interactions. To overcome this resistance, virulent larvae
      appeared to suppress antibiosis defense while inducing nutrient metabolism,
      weakening cell wall, and inhibiting plant growth.

PMID- 18058178
TI  - Honeybee (Apis cerana) foraging responses to the toxic honey of Tripterygium
      hypoglaucum (Celastraceae): changing threshold of nectar acceptability.
AB  - To investigate honeybee foraging responses to toxic nectar, honey was collected
      from Apis cerana colonies in the Yaoan county of Yunnan Province, China, during
      June, when flowers of Tripterygium hypoglaucum were the main nectar source
      available. Pollen analysis confirmed the origin of the honey, and high
      performance liquid chromatography showed the prominent component triptolide to be
      present at a concentration of 0.61 mug/g +/- 0.11 SD. In cage tests that used
      young adult worker bees, significantly more of those provided with a diet of T.
      hypoglaucum honey mixed with sugar powder (1:1) died within 6 d (68.3%) compared
      to control groups provided with normal honey mixed with sugar powder (15.8%).
      Honeybees were trained to visit feeders that contained honey of T. hypoglaucum
      (toxic honey) as the test group and honey of Vicia sativa or Elsholtzia ciliata
      as control groups (all honeys diluted 1:3 with water). Bees preferred the feeders
      with normal honey to those with toxic honey, as shown by significantly higher
      visiting frequencies and longer imbibition times. However, when the feeder of
      normal honey was removed, leaving only honey of T. hypoglaucum, the foraging bees
      returned to the toxic honey after a few seconds of hesitation, and both visiting
      frequency and imbibition time increased to values previously recorded for normal
      honey. Toxic honey thus became acceptable to the bees in the absence of other
      nectar sources.

PMID- 18058179
TI  - Complications of neck dissection for thyroid cancer.

PMID- 18058180
TI  - Locally advanced GISTs need aggressive therapy pending the results of trials.

PMID- 18058181
TI  - Advances in laparoscopic gastrectomy expand clinical use.

PMID- 18058182
TI  - The influence of age on the breast surgery decision-making process.
AB  - BACKGROUND: Mastectomy rates have been assumed to be a function of physician
      recommendations, although they correlate with patient involvement in decision
      making. The influence of age on the decision-making process and treatment choice
      is poorly described. METHODS: All women with ductal carcinoma in situ (DCIS) and
      a random sample with invasive breast cancer were identified from two Surveillance
      Epidemiology and End Results (SEER) program registries and surveyed 6 months
      postoperatively. Women older than 79 years with noninvasive or localized invasive
      breast cancer diagnosed in 2002 were included. Women with breast-conserving
      therapy (BCT) contraindications were excluded. Women were questioned about
      involvement in surgical decision-making, inquiring if this decision was patient
      based, surgeon-based, or shared. Knowledge and concerns were assessed. RESULTS:
      The response rate was 77.0%. There were 1,259 patients who met the study
      eligibility criteria and age data was available for 1,131. Median patient age was
      59.9 years. The frequency of patient-based decisions did not vary with age (p =
      0.20), but older women had less knowledge for decision making. The mastectomy
      rate overall was 19.7%, with no differences in mastectomy choice by age (p =
      0.18). In logistic regression for the likelihood of undergoing mastectomy,
      patient involvement (p < 0.0001), larger tumor size (p < 0.0001), lower education
      (p = 0.0002), number of surgeons consulted (p = 0.0005), and nonwhite race origin
      (p = 0.011) were significant predictors, while age, invasion, and comorbidities
      were not significant. CONCLUSION: Older women participate equally in breast
      cancer surgical decision making and are equally likely to select mastectomy, but
      use less knowledge to make the decision. The impact of education and ethnic
      origin on mastectomy use indicates the need for improved educational strategies
      for these groups.

PMID- 18058183
TI  - Factors influencing pathologic results after total mesorectal excision for rectal
      cancer: analysis of consecutive 100 cases.
AB  - BACKGROUND: The aim of this study was to analyze clinical and anatomical factors
      affecting the pathologic quality of the resected specimen after total mesorectal
      excision (TME) for rectal cancer. METHODS: A total of 100 patients who underwent
      TME for mid or low rectal cancer were evaluated prospectively. MRI pelvimetry
      data (transverse diameter, obstetric conjugate, interspinous distance, sacrum
      length, and sacrum depth) were analyzed as anatomically affecting factors to
      postoperative specimen quality. Sex, body mass index (BMI), type of surgery,
      tumor size, and tumor distance from the anal verge were analyzed as clinically
      affecting factors. The gross judgment of resected specimen, circumferential
      resection margin and the number of harvested lymph nodes were used to access
      postoperative specimen quality. RESULTS: The univariate and multivariate analysis
      showed that narrow obstetric conjugate and shorter interspinous distance were
      related to the inadequate quality of the mesorectum in the specimen (P = 0.022, P
      = 0.030). Interspinous distance was a predicting factor of a positive
      circumferential resection margin (P = 0.007). There were no clinical factors
      affecting the inadequate quality of the mesorectum or positive circumferential
      resection margin. Moreover, there were no clinico-anatomical factors affecting
      the number of harvested lymph nodes after TME. CONCLUSION: Narrow obstetric
      conjugate and shorter interspinous distance were factors leading to poor
      postoperative specimen quality. Rectal cancer patients with narrow obstetric
      conjugate or shorter interspinous distance should be considered as high-risk
      patients with regard to specimen quality, which is in turn related to oncological
      outcome.

PMID- 18058184
TI  - Detection and description of small breast masses by residents trained using a
      standardized clinical breast exam curriculum.
AB  - OBJECTIVES: We evaluated the effect of standardized clinical breast examination
      (CBE) training on residents' ability to detect a 3-mm breast mass in a silicone
      breast model. METHODS: In this nonrandomized controlled trial, 75 first year
      residents (R1s) at 8 family medicine, internal medicine, and obstetrics and
      gynecology training programs received the intervention and second year residents
      (R2s) did not. Trained residency faculty taught R1s vertical strip, three
      pressure method (VS3PM) CBE using a standardized curriculum, including a 1- to 2
      hour online self-study with video and 2.5-hour practicum using silicone models
      and a trained patient surrogate. RESULTS: Solitary mass detection: 84% by R1s,
      46% by R2s (RR = 1.82, 95%CI = 1.36, 2.43, P < 0.0001). Of those finding a mass,
      62% of R1s and 10% of R2s used at least 5 of 8 standardized descriptors (RR =
      6.19, 95%CI = 2.06, 18.59, P = 0.001). R1s false positive findings were not
      statistically different from R2s (P = 0.54). Both the use of VS3PM and total time
      spent on CBE were independently highly predictive of finding the mass in either
      group. CONCLUSIONS: Most untrained primary care residents are not proficient in
      CBE. Standardized VS3PM CBE training improves the ability to detect and describe
      a small mass in a silicone breast model. Better CBE training for residents may
      improve the early detection of breast cancer.

PMID- 18058185
TI  - Defining the role of surgery for primary gastrointestinal tract melanoma.
AB  - OBJECTIVE: The objective of the study was to determine the outcomes for primary
      gastrointestinal melanomas (PGIM). MATERIAL AND METHODS: The Surveillance,
      Epidemiology, and End Results database (1973-2004) was queried. RESULTS: Overall,
      659 cases of PGIM were identified. The annual incidence of PGIM was approximately
      0.47 cases per million in 2000. Overall median survival time was 17 months.
      Tumors were identified in the oral-nasopharynx (32.8%), anal canal (31.4%),
      rectum (22.2%), esophagus (5.9%), stomach (2.7%), small bowel (2.3%), gallbladder
      (1.4%), and large bowel (0.9%). Univariate analysis demonstrated age, tumor
      location, stage, surgery, and lymph node status were significant predictors of
      improved survival. MST has not been reached for tumors located in the large
      bowel, while tumors located in the stomach demonstrated the shortest median
      survival (5 months). Improvement in MST was observed for those patients
      undergoing surgical resection. The presence of lymph node involvement conferred a
      poorer prognosis. Multivariate analysis of the cohort identified that location,
      advanced tumor stage, failure to undertake surgical resection, positive lymph
      node status, and age were all independent predictors of poorer outcome.
      CONCLUSION: PGIM occurs most often in the oral-nasopharynx and anal canal.
      Surgical extirpation is the only identifiable treatment modality that
      significantly improves survival.

PMID- 18058186
TI  - Risk factors of postoperative anastomotic stricture after excision of choledochal
      cysts with hepaticojejunostomy.
AB  - The aim of this study was to investigate the risk factors of postoperative
      anastomotic stricture after excision of choledochal cysts and
      hepaticojejunostomy. Among 65 patients who underwent surgery for choledochal cyst
      between March 1995 and June 2005, we selected 34 adult patients who were
      diagnosed as having choledochal cyst. We divided patients into two groups,
      depending on postoperative anastomotic stricture developed or not. Medical
      records and radiological findings of each patient were reviewed retrospectively.
      H&E stain and Masson-Trichrome stain of each specimen of the resected cyst were
      performed, and thickness of cyst wall, the grade of fibrosis, loss of smooth
      muscle layer, loss of mucosa, and infiltration of inflammatory cells were
      measured. Of the 34 patients, excision of choledochal cyst and
      hepaticojejunostomy were done in 33 patients, and 1 patient with chronic
      pancreatitis underwent pylorus-preserving pancreaticoduodenectomy. Anastomotic
      stricture and intrahepatic duct stones postoperatively developed in eight
      patients; one patient of 19 type I cyst and seven patients of 15 type IVa,
      developing significantly more in the type IVa choledochal cyst (P<0.05). The size
      of choledochal cyst in the stricture group was 7.0 cm, and that of the non
      stricture group, 4.2 cm, showing significant difference between the two groups
      (P<0.05). The stricture group presented shorter duration of symptoms (27.63+/
      61.72 days; ranged, 1 approximately 180 days) than the non-stricture group
      (483.33+/-916.41 days; ranged, 1 approximately 3,560 days), and it was
      statistically significant (P<0.05). Pathologically, significant difference was
      found between anastomotic stricture and infiltration of inflammatory cells
      (P<0.05). The results indicate that anastomotic stricture is influenced by the
      type IVa choledochal cyst, size of cyst, duration of symptoms, and the grade of
      infiltration of inflammatory cells. Therefore, closed careful follow-up is
      important in patients who underwent cyst excision with hepaticojejunostomy for
      type IVa choledochal cyst. If the anastomotic stricture develops, nonoperative
      management should be recommended, rather than operation, as much as possible.

PMID- 18058187
TI  - Micro-hardness evaluation of a micro-hybrid composite resin light cured with
      halogen light, light-emitting diode and argon ion laser.
AB  - This in vitro study aimed to determine whether the micro-hardness of a composite
      resin is modified by the light units or by the thickness of the increment.
      Composite resin disks were divided into 15 groups (n = 5), according to the
      factors under study: composite resin thickness (0 mm, 1 mm, 2 mm , 3 mm and 4 mm)
      and light units. The light activation was performed with halogen light (HL) (40
      s, 500 mW/cm(2)), argon ion laser (AL) (30 s, 600 mW/cm(2)) or light-emitting
      diode (LED) (30 s, 400 mW/cm(2)). Vickers micro-hardness tests were performed
      after 1 week and were carried out on the top surface (0 mm-control) and at
      different depths of the samples. Analysis of variance (ANOVA) and Tukey tests (P
      < or = 0.05) revealed no statistically significant difference among the light
      units for the groups of 0 mm and 1 mm thickness. At 2 mm depth, the AL was not
      statistically different from the HL, but the latter showed higher micro-hardness
      values than the LED. In groups with 3 mm and 4 mm thickness, the HL also showed
      higher micro-hardness values than the groups activated by the AL and the LED.
      Only the HL presented satisfactory polymerization with 3 mm of thickness. With a
      4 mm increment no light unit was able to promote satisfactory polymerization.

PMID- 18058189
TI  - Significance of exine shedding in Cupressaceae-type pollen.
AB  - In conifers, which have non-saccate Cupressaceae-type pollen, the pollen must
      land on a pollination drop or be picked up by the pollination drop from the
      surface of the cone near the ovule before it can be taken into the ovule. After
      contact with the drop, the pollen intine absorbs moisture from the drop, expands
      and the exine is shed. In this study the significance of the shedding of the
      exine is interpreted from experiments in which simulated pollination drops and
      micropyles were used to determine the movement of pollen and other particles in
      suspension. The non-expanded pollen, which can be observed upon contact with the
      pollination drop, sheds the exine, which then functions as a non-elastic
      particle, while the pollen from which the exine was shed swells and functions as
      an elastic particle because it is enclosed by the flexible intine. Non-elastic
      particles are not easily transferred through narrow passages (the micropyle and
      micropylar canal) and tend to plug these passages. However, elastic particles,
      such as the swollen pollen, are easily transferred along narrow passages even
      when non-elastic particles are present. The simulated experiments demonstrate
      that exine shedding is an important feature in getting pollen through the narrow
      micropyle and micropylar canal to the nucellus of the ovule.

PMID- 18058188
TI  - Analysis of c-myc, PAI-1 and uPAR in patients with incisional hernias.
AB  - BACKGROUND: Disturbed wound healing leading to alterations in collagen
      composition has been thought to play a key role in the pathogenesis of incisional
      hernia formation. The aim of the present study was to further characterise the
      scarring process in such patients. METHODS: Mature skin scars from patients with
      either primary or recurrent incisional hernias were compared to mature abdominal
      skin scars from patients without hernias. The distribution of collagen types I
      and III was analysed using crosspolarisation microscopy. Expression of c-myc--a
      parameter for cell differentiation and proliferation--and of PAI-1 and uPAR-
      parameters of the proteolytic cascade in wound healing--were determined by
      immunohistochemistry. RESULTS: In agreement with previous studies, decreased
      collagen I/III ratios were found in patients with incisional hernias. In these
      patients, c-myc levels were significantly elevated whereas plasminogen activator
      inhibitor-1 (PAI-1) and urokinase-plasminogen activator receptor (uPAR) levels
      were only slightly increased. In contrast to controls, a significant correlation
      between c-myc, PAI-1 and uPAR expression and collagen I/III ratios was found in
      patients with incisional hernias. CONCLUSION: The differential correlation of
      collagen types and expression of c-myc, PAI-1 and uPAR within the scar tissue
      might represent a causal factor in incisional hernia formation.

PMID- 18058190
TI  - Thermogenesis and flowering biology of Colocasia gigantea, Araceae.
AB  - The thermogenesis and flowering biology of Colocasia gigantea (Blume) Hook. f.
      were studied from December 2005 to February 2006 on Espiritu Santo, Vanuatu
      (South Pacific). Endogenous thermogenesis was measured in two ways: (1)
      continuously over 5-day periods, and (2) over 3 h during maximum heating. The
      study showed that heat was generated by the male part of the spadix and probably
      the lower zone of the sterile region. The temperatures of the male part peaked
      twice: (1) between 0625 and 0640 (during the female phase) and (2) 24 h later
      (during the male phase). The average maximum temperature was 42.25 +/- 0.14
      degrees C during the female phase (16.63 degrees C above the ambient temperature)
      and 35.14 +/- 0.22 degrees C during the male phase (10.61 degrees C above the
      ambient temperature). In the lower zone of the sterile region, thermogenesis was
      documented only during the female phase. The average maximum temperature was
      35.44 +/- 0.41 degrees C (9.82 degrees C above the ambient temperature).
      Thermogenic heating appeared to be closely associated with the activities of
      pollinating insects.

PMID- 18058191
TI  - Airborne sperm of Conocephalum conicum (Conocephalaceae).
AB  - We have obtained the first momentary photographs of sperms just as they are
      discharged from the antheridium of a liverwort, Conocephalum conicum, and have
      succeeded in monitoring the airborne sperms of bryophytes under field conditions.
      Airborne sperm of liverworts seems to be an effective strategy for raising the
      efficiency of fertilization between male and female plants separated in a drought
      environment.

PMID- 18058192
TI  - The 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is not
      associated with HELLP syndrome.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is a major inhibitor of fibrinolysis,
      and a single nucleotide insertion/deletion (4G/5G) polymorphism in the promoter
      region of the PAI-1 gene has been identified. Subjects homozygous for the 4G
      allele have the highest PAI-levels due to increased PAI-1 gene transcription. Pre
      eclampsia, and one of its most severe forms, the HELLP (hemolysis, elevated liver
      enzymes, low platelets) syndrome, are characterized by increased placental
      thrombosis based on a procoagulatory state in the mother. Several studies have
      investigated the role of the PAI-1 4G/5G polymorphism in pre-eclampsia, but no
      study has focused especially on HELLP syndrome. Therefore we aimed to assess the
      association between HELLP syndrome and the 4G/5G polymorphism in the PAI-1 gene.
      Genotyping of the PAI-1 4G/5G promoter polymorphism was performed in 102
      Caucasian women with HELLP syndrome and 102 Caucasian women with uncomplicated
      pregnancies. The 4G/4G genotype was more frequent in women with HELLP syndrome
      than in controls (35.3% vs. 22.5%, respectively) but this difference was not
      significantly different (P = 0.129). The frequency of the 4G allele was 0.588 in
      patients and 0.515 in controls. These data suggest that women carrying a 4G/4G
      genotype of the PAI-1 gene are not at increased risk for developing HELLP
      syndrome and are thus in line with the majority of previous studies on the
      association between the PAI-1 4G/5G polymorphism and pre-eclampsia.

PMID- 18058193
TI  - Al-toxicity studies in yeast using gallium as an aluminum analogue.
AB  - Aluminum (Al) is normally present in soils as the insoluble, harmless Al2O3. The
      highly toxic Al3+ and AlOH2+ monomeric cations are formed in acid soils but there
      is little consensus on the physiological basis of Al toxicity in plants. A major
      factor that has retarded progress in understanding aluminum toxicity in vascular
      plants is the lack of a convenient radioisotope for Al. Yeast and vascular plants
      share similar membrane transport mechanisms and so yeast (Saccharomyces
      cerevisiae) provides a convenient model system for studies of Al-toxicity. Al and
      gallium (Ga) have closely similar toxic effects on the yeast cells (Ki
      approximately 100 mmol m-3) and Ga3+ and Al3+, respond similarly to pH and are
      both reversible by a chelation agent (citric acid). We tested the feasibility of
      using 67Ga radioisotope as a tracer for Al transport with the view of using it to
      investigate the mechanism of Al uptake and toxicity in plants. The clinically
      available 67Ga citrate is unsuitable to use as an aluminum analogue because the
      chelated form is not toxic. Arrangements need to be made for it to be supplied as
      67GaCl3. Large amounts of 67Ga rapidly bind to the cell wall of yeasts with a t
      1/2 of approximately 1 s. There is a very slow net uptake of 67Ga into a second
      phase, presumably the cytoplasm. Uptake into the slow phase has a Vmax of only
      approximately 16 +/- 4 pmol m(-2) s(-1) (n = 16). The Km of 67Ga uptake could not
      be precisely determined but is below 100 mmol m(-3) (45 +/- 42 mmol m(-3), n =
      16).

PMID- 18058194
TI  - Identification, isolation, and analysis of a gene cluster involved in iron
      acquisition by Pseudomonas mendocina ymp.
AB  - Microbial acquisition of iron from natural sources in aerobic environments is a
      little-studied process that may lead to mineral instability and trace metal
      mobilization. Pseudomonas mendocina ymp was isolated from the Yucca Mountain Site
      for long-term nuclear waste storage. Its ability to solubilize a variety of Fe
      containing minerals under aerobic conditions has been previously investigated but
      its molecular and genetic potential remained uncharacterized. Here, we have shown
      that the organism produces a hydroxamate and not a catecholate-based siderophore
      that is synthesized via non-ribosomal peptide synthetases. Gene clustering
      patterns observed in other Pseudomonads suggested that hybridizing multiple
      probes to the same library could allow for the identification of one or more
      clusters of syntenic siderophore-associated genes. Using this approach, two
      independent clusters were identified. An unfinished draft genome sequence of P.
      mendocina ymp indicated that these mapped to two independent contigs. The
      sequenced clusters were investigated informatically and shown to contain
      respectively a potentially complete set of genes responsible for siderophore
      biosynthesis, uptake, and regulation, and an incomplete set of genes with low
      individual homology to siderophore-associated genes. A mutation in the cluster's
      pvdA homolog (pmhA) resulted in a siderophore-null phenotype, which could be
      reversed by complementation. The organism likely produces one siderophore with
      possibly different isoforms and a peptide backbone structure containing seven
      residues (predicted sequence: Acyl-Asp-Dab-Ser-fOHOrn-Ser-fOHorn). A similar
      approach could be applied for discovery of Fe- and siderophore-associated genes
      in unsequenced or poorly annotated organisms.

PMID- 18058195
TI  - The tumor microenvironment: regulation by MMP-independent effects of tissue
      inhibitor of metalloproteinases-2.
AB  - Proteolytic remodeling of the extracellular matrix is an important component of
      disease progression in many chronic disease states and is the initiating event in
      the formation of the tumor microenvironment in cancer. It is the balance of
      extracellular matrix degrading enzymes, the matrix metalloproteinases (MMPs) and
      their endogenous inhibitors that determine the extent of tissue remodeling.
      Unchecked MMP activity can result in significant tissue damage, facilitate
      disease progression and is associated with host responses to pathologic injury
      such as angiogenesis and inflammation. The tissue inhibitors of
      metalloproteinases (TIMPs) have been shown to regulate MMP activity. However,
      recent findings demonstrate that the tissue inhibitor of metalloproteinases-2
      (TIMP-2) inhibits the mitogenic response of human microvascular endothelial cells
      to growth factors, such as VEGF-A and FGF-2 in vitro and angiogenesis in vivo.
      The mechanism of this effect is independent of metalloproteinase inhibition. Our
      lab is the first to demonstrate a cell-surface signaling receptor for a member of
      the TIMP family and suggest that TIMP-2 functions to regulate cellular responses
      to growth factors. These new findings are discussed in terms of a model of TIMP-2
      regulation of cellular functions in the tumor microenvironment.

PMID- 18058196
TI  - In vitro behavior of osteoblast-like cells on PLLA films with a biomimetic
      apatite or apatite/collagen composite coating.
AB  - To investigate the methods to improve the cell-material interaction of devices or
      tissue engineering scaffolds made of poly(L-lactic acid) (PLLA) polymer, apatite
      and apatite/collagen composite coatings were formed on PLLA films within 24 h
      through accelerated biomimetic processes. In vitro investigation using Saos-2
      osteoblast-like cells through cell culture was conducted to assess the biological
      performance of these biomimetic coatings. The cell morphology on three types of
      surfaces, viz., PLLA film, PLLA film with the apatite coating, and PLLA film with
      the apatite/collagen composite coating, was studied using scanning electron
      microscopy (SEM). Cell viability was estimated using the MTT assay. The
      differentiated cell function was assessed by measuring the alkaline phosphatase
      (ALP) activity. The results obtained indicated that the biomimetic apatite and
      apatite/collagen composite coatings could significantly enhance the proliferation
      and differentiation of osteoblast-like cells. The apatite/collagen composite
      coating appears to be promising for the surface modification of PLLA-based
      devices with much improved interactions with osteoblastic cells.

PMID- 18058197
TI  - PLD bioactive ceramic films: the influence of CaO-P2O5 glass additions to
      hydroxyapatite on the proliferation and morphology of osteblastic like-cells.
AB  - This work consists on the evaluation of the in vitro performance of Ti6Al4V
      samples PLD (pulsed laser deposition) coated with hydroxyapatite, both pure and
      mixed with a CaO-P2O5 glass. Previous studies on immersion of PLD coatings in
      SBF, showed that the immersion apatite films did not present the usual
      cauliflower morphology but replicated the original columnar structure and
      exhibited good bioactivity. However, the influence of glass associated to
      hydroxyapatite concerning adhesion, proliferation and morphology of MG63 cells on
      the films surface was unclear. In this study, the performance of these PLD coated
      samples was evaluated, not only following the physical-chemical transformations
      resulting from the SBF immersion, but also evaluating the cytocompatibility in
      contact with osteoblast-like MG63 cells. SEM and AFM confirmed that the bioactive
      ceramic PLD films reproduce the substrate's surface topography and that the films
      presented good adherence and uniform surface roughness. Physical-chemical
      phenomena occurring during immersion in SBF did not modify the original columnar
      structure. In contact with MG63 cells, coated samples exhibited very good
      acceptance and cytocompatibility when compared to control. The glass mixed with
      hydroxyapatite induced higher cellular proliferation. Cells grown on these
      samples presented many filipodia and granular structures, typical features of
      osteoblasts.

PMID- 18058198
TI  - Apatite-forming ability of polyglutamic acid hydrogels in a body-simulating
      environment.
AB  - Artificial joints can replace damaged joints provided the surrounding bone is
      sufficiently dense. However, elderly patients generally have reduced osteoporosis
      associated bone density. Therefore, restitution of bone density is essential to
      ensure implantation. Injectable and resorbable bioactive fillers with bone
      bonding ability (osteoconductivity) are promising, as osteoporosis can be
      reversed with minimal invasion. Osteoconduction occurs through the surface
      formation of biologically active hydroxyapatite via reactions with body fluids.
      Heterogeneous nucleation of the hydroxyapatite is catalysed by specific surface
      functional groups. In addition, release of Ca2+ ions into the surrounding fluids
      enhances apatite nucleation by increasing its degree of supersaturation. We
      tested injectable bioactive filler made from cross-linked polyglutamic acid
      (PGA). This has many carboxyl groups that facilitate apatite nucleation. An
      insoluble hydrogel can be formed by cross-linkage. We exposed PGA gels to a
      simulated body fluid for 7 days. Trace amounts of calcium phosphate were formed,
      but were not identified as bone-like apatite by X-ray diffraction. However,
      formation of a bone-like apatite layer was detected using pre-treatment with
      CaCl2 solutions (>0.01 mol dm(-3)) dose dependently. Thus, this chemically cross
      linked PGA gel could induce the heterogeneous nucleation of hydroxyapatite in a
      body environment, and this was enhanced by pre-treatment with CaCl2.

PMID- 18058199
TI  - Hydrogel-elastomer composite biomaterials: 4. Experimental optimization of
      hydrogel-elastomer composite fibers for use as a wound dressing.
AB  - We report a novel 3-D cavity wound dressing based on a hydrogel-elastomer
      Interpenetrating Polymer Network (IPN) fabricated into an open-mesh architecture.
      IPN fibers used to form the dressing were produced by a wet spinning method and
      optimized in two steps. A factorial experiment was first conducted to identify
      key parameters that controlled fiber properties. We observed that gelatin wt%
      played a major role in determining fiber yield, swelling, strength and stability.
      Other contributing factors included coagulation solution composition, gelatin
      type, and pre- and post-UV irradiation time. The key factors were then further
      evaluated individually to achieve a condition that provided a combination of good
      swelling, mechanical properties and stability. The concentration of the
      gelatin/HydroThane extrusion solution significantly affected fiber formation and
      properties, presumably due to the changes in solution viscosity. The effects of
      pre-UV irradiation were also ascribed to its impact on the solution viscosity and
      became negligible at higher concentrations when viscosity is mainly controlled by
      concentration. The composition of the coagulation bath influenced the fiber
      swelling and wet stress. These results, taken together with our previous studies,
      suggest that our biomaterial would provide a combination of mechanical and
      swelling properties suitable for wound dressing applications.

PMID- 18058200
TI  - Preparation and characterization of amidated pectin based hydrogels for drug
      delivery system.
AB  - In the current studies attempts were made to prepare hydrogels by chemical
      modification of pectin with ethanolamine (EA) in different proportions.
      Chemically modified pectin products were crosslinked with glutaraldehyde reagent
      for preparing hydrogels. The hydrogels were characterized by Fourier transform
      infrared spectroscopy (FTIR), organic elemental analysis, X-ray diffraction
      studies (XRD), swelling studies, biocompatibility and hemocompatibility studies.
      Mechanical properties of the prepared hydrogels were evaluated by tensile test.
      The hydrogels were loaded with salicylic acid (used as a model drug) and drug
      release studies were done in a modified Franz's diffusion cell. FTIR spectroscopy
      indicated the presence of primary and secondary amide absorption bands. XRD
      studies indicated increase in crystallinity in the hydrogels as compared to
      unmodified pectin. The degree of amidation (DA) and molar and mass reaction
      yields (YM and YN) was calculated based on the results of organic elemental
      analysis. The hydrogels showed good water holding properties and were found to be
      compatible with B-16 melanoma cells & human blood.

PMID- 18058201
TI  - EDC/NHS-crosslinked type II collagen-chondroitin sulfate scaffold:
      characterization and in vitro evaluation.
AB  - Three-dimensional biodegradable porous type II collagen scaffolds are interesting
      materials for cartilage tissue engineering. This study reports the preparation of
      porous type II collagen-chondroitin sulfate (CS) scaffold using variable
      concentrations of 1-ethyl-3(3-dimethyl aminopropyl) carbodiimide (EDC) and N
      hydroxysuccinimide (NHS). The physico-chemical properties and ultrastructural
      morphology of the collagen scaffolds were determined. Then, isolated chondrocytes
      were cultured in porous type II collagen scaffolds either in the presence and/or
      absence of covalently attached CS up to 14 days. Cell proliferation, the total
      amount of proteoglycans and type II collagen retained in the scaffold and
      chondrocytes morphology were evaluated. The results suggest that EDC-crosslinking
      improves the mechanical stability of collagen-CS scaffolds with increasing EDC
      concentration. Cell proliferation and the total amount of proteoglycans and type
      II collagen retained in the scaffolds were higher in type II collagen-CS
      scaffolds. Histological analysis showed the formation of a denser cartilaginous
      layer at the scaffold periphery. Scanning electron microscopy (SEM) revealed
      chondrocytes distributed the porous surface of both scaffolds maintained their
      spherical morphology. The results of the present study also indicate that type II
      collagen-CS scaffolds have potential for use in tissue engineering.

PMID- 18058203
TI  - Exposure-response modeling using latent variables for the efficacy of a JAK3
      inhibitor administered to rheumatoid arthritis patients.
AB  - Currently, no general methods have been developed to relate pharmacologically
      based models, such as indirect response models, to discrete or ordered
      categorical data. We propose the use of an unobservable latent variable (LV),
      through which indirect response models can be linked with drug exposure. The
      resulting indirect latent variable response model (ILVRM) is demonstrated using a
      case study of a JAK3 inhibitor, which was administered to patients in a
      rheumatoid arthritis (RA) study. The clinical endpoint for signs and symptoms in
      RA is the American College of Rheumatology response criterion of 20%--a binary
      response variable. In this case study, four exposure-response models, which have
      different pharmacological interpretations, were constructed and fitted using the
      ILVRM method. Specifically, two indirect response models, an effect compartment
      model, and a model which assumes instantaneous (direct) drug action were assessed
      and compared for their ability to predict the response data. In general,
      different model interpretations can influence drug inference, such as time to
      drug effect onset, as well as affect extrapolations of responses to untested
      experimental conditions, and the underlying pharmacology that operates to
      generate key response features does not change because the response was measured
      discretely. Consideration of these model interpretations can impact future study
      designs and ultimately provide greater insight into drug development strategies.

PMID- 18058202
TI  - On the rate and extent of drug delivery to the brain.
AB  - To define and differentiate relevant aspects of blood-brain barrier transport and
      distribution in order to aid research methodology in brain drug delivery.
      Pharmacokinetic parameters relative to the rate and extent of brain drug delivery
      are described and illustrated with relevant data, with special emphasis on the
      unbound, pharmacologically active drug molecule. Drug delivery to the brain can
      be comprehensively described using three parameters: Kp,uu (concentration ratio
      of unbound drug in brain to blood), CLin (permeability clearance into the brain),
      and Vu,brain (intra-brain distribution). The permeability of the blood-brain
      barrier is less relevant to drug action within the CNS than the extent of drug
      delivery, as most drugs are administered on a continuous (repeated) basis. Kp,uu
      can differ between CNS-active drugs by a factor of up to 150-fold. This range is
      much smaller than that for log BB ratios (Kp), which can differ by up to at least
      2,000-fold, or for BBB permeabilities, which span an even larger range (up to at
      least 20,000-fold difference). Methods that measure the three parameters Kp,uu,
      CLin, and Vu,brain can give clinically valuable estimates of brain drug delivery
      in early drug discovery programmes.

PMID- 18058204
TI  - 5,9-Diaminodibenzo[a,j]phenoxazinium chloride: a rediscovered efficient long
      wavelength fluorescent dye.
AB  - We have evaluated the chemical, photophysical and photostability properties of
      5,9-diaminodibenzo[a,j]phenoxazinium chloride, 3, and its bis-5,9-ethylamino
      analogue, 4, with the goal of determining if they have characteristics that are
      compatible with the requirements of a useful fluorescent probe. In order to gauge
      the potential utility of these fluorophores in biological and non-biological
      applications, these data were compared to those obtained for Oxazine 118, 1, and
      Cresyl Violet, 2, two well known fluorescent dyes that differ in molecular
      structure from the title dye 3 by having two or one fewer benzo moieties fused to
      a generic oxazine ring structure, respectively. The findings of this
      investigation show that 3, as well as bis-ethylamino analogue, 4, have
      fluorescent lifetimes, quantum yields and photostabilities that compare favorably
      with the lower order benchmark fluorophores 1 and 2. Moreover, both dibenzo dyes
      have the highly desirable properties of absorbing and emitting further in the red
      and far red /near infrared spectral region, respectively, than do their less
      conjugated analogues. Taken together, these results suggest that 3 constitutes an
      archetype upon which a new class of long wavelength fluorescent reporters might
      be based.

PMID- 18058205
TI  - Binding of puerarin to human serum albumin: a spectroscopic analysis and
      molecular docking.
AB  - Puerarin is a widely used compound in Chinese traditional medicine and exhibits
      many pharmacological activities. Binding of puerarin to human serum albumin (HSA)
      was investigated by ultraviolet absorbance, fluorescence, circular dichroism and
      molecular docking. Puerarin caused a static quenching of intrinsic fluorescence
      of HSA, the quenching data was analyzed by Stern-Volmer equation. There was one
      primary puerarin binding site on HSA with a binding constant of 4.12 x 10(4) M(
      1) at 298 K. Thermodynamic analysis by Van Hoff equation found enthalpy change
      (DeltaH(0)) and entropy change (DeltaS(0)) were -28.01 kJ/mol and -5.63 J/mol K
      respectively, which indicated the hydrogen bond and Van der Waas interaction were
      the predominant forces in the binding process. Competitive experiments showed a
      displacement of warfarin by puerarin, which revealed that the binding site was
      located at the drug site I. Puerarin was about 2.22 nm far from the tryptophan
      according to the observed fluorescence resonance energy transfer between HSA and
      puerarin. Molecular docking suggested the hydrophobic residues such as tyrosine
      (Tyr) 150, Tyr 148, Tyr 149 and polar residues such as lysine (Lys) 199, Lys 195,
      arginine 257 and histidine 242 played an important role in the binding reaction.

PMID- 18058207
TI  - Affirming the existential within medicine: medical humanities, governance, and
      imaginative understanding.
AB  - This paper first distinguishes governance (collective, autonomous self-regulatory
      processes) from government (externally-imposed mandatory regulation); it proposes
      that the second of these is essentially incompatible with a conception of the
      medical humanities that involves imagination and vision on the part of medical
      practitioners. It next develops that conception of the medical humanities, as
      having three distinguishable aspects (all of them distinct from the separate
      phenomena popularly known as "arts-in-health"): first, an intellectual enquiry
      into the nature of clinical medicine; second, an important dimension of medical
      education; third, a resource for moral and aesthetic influences upon clinical
      practice, supporting "humane health care" as the moral inspirations behind
      organised medicine. Medical humanities sustains these three aspects through
      paying proper attention to the existential and subjective aspects of medicine. By
      encouraging authentic imagination among health care practitioners, medical
      humanities aligns well with both humane health care and governance in the sense
      of self-regulation. However, it can neither be achieved mechanistically nor well
      measured through proxies such as patient satisfaction. Above all, it should not
      be allowed to supply, through inappropriate qualitative "targets," new forms of
      management tyranny.

PMID- 18058206
TI  - Spectrofluorimetric determination of oxamniquine in dosage forms and spiked human
      plasma through derivatization with 1-dimethylaminonaphthalene-5-sulphonyl
      chloride.
AB  - A sensitive, simple and selective spectrofluorimetric method was developed for
      the determination of oxamniquine (OXM) in pharmaceutical formulations and
      biological fluids. The method is based on the reaction between the drug and 1
      dimethylaminonaphthalene-5-sulphonyl chloride (dansyl chloride) in presence of
      0.5 M sodium carbonate (pH 10) to yield a highly fluorescent derivative that is
      measured at 445 nm after excitation at 335 nm. The different experimental
      parameters affecting the development and stability of the reaction product were
      carefully studied and optimized. The fluorescence concentration plot was
      rectilinear over the range of 0.02-0.2 microg ml(-1) with a lower detection limit
      (LOD) of 0.007 microg ml(-1) and limit of quantitation (LOQ) of 0.02 microg ml(
      1). The proposed method was successfully applied to the analysis of commercial
      capsules. The results obtained were in good agreement with those obtained using
      the official spectrophotometric method. Furthermore, the method was applied for
      the determination of oxamniquine in spiked human plasma, the mean % recovery (n =
      4) is 97.77 +/- 1.19. A proposal of the reaction pathway was presented.

PMID- 18058208
TI  - Striving to do good things: teaching humanities in Canadian medical schools.
AB  - We provide the results of a systematic key-informant review of medical humanities
      curricula at fourteen of Canada's seventeen medical schools. This survey was the
      first of its kind. We found a wide diversity of views among medical educators as
      to what constitutes the medical humanities, and a lack of consensus on how best
      to train medical students in the field. In fact, it is not clear that consensus
      has been attempted - or is even desirable - given that Canadian medical
      humanities programs are largely shaped by individual educators' interests,
      experience and passions. This anarchic approach to teaching the medical
      humanities contrasts sharply with teaching in the clinical sciences where
      national accreditation processes attempt to ensure that doctors graduating from
      different schools have roughly the same knowledge (or at least have passed the
      same exams). We argue that medical humanities are marginalized in Canadian
      curricula because they are considered to be at odds philosophically with the
      current dominant culture of evidence-based medicine (EBM). In such a culture
      where adhering to a consensual standard is a measure of worth, the medical
      humanities - which defy easy metrical appraisal - are vulnerable. We close with a
      plea for medical education to become more comfortable in the borderlands between
      EBM and humanities approaches.

PMID- 18058209
TI  - Words and flesh in the NHS.
AB  - Working as a clinician within the National Health Service (NHS) in England is
      described along with the difficulty of identifying a role for the humanities
      within the organisational framework. The author argues that the humanities are
      both marginalised and required and that the humanities can provide a means to
      redefine values within medical practice.

PMID- 18058210
TI  - Training community health workers to be advocates for health promotion: efforts
      taken by a community-based organization to reduce health disparities in
      cardiovascular disease.
AB  - Compared to white adults, blacks are less likely to be aware of their
      cardiovascular risk factors and are less likely to respond appropriately to signs
      and symptoms of a myocardial infarction or stroke. This fact highlights the need
      for better dissemination of health information about cardiovascular disease among
      communities of color. Community health workers (CHWs) are important resources for
      disseminating health information. Recognizing this important role of CHWs, the
      Greater Southern Brooklyn Health Coalition and its community and academic
      partners developed a workshop designed to educate CHWs about the risk factors,
      signs and symptoms of cardiovascular disease. The purpose of this workshop was to
      educate CHWs so that they themselves could be better informed and thus, be in a
      better position to educate their respective clients. The resulting workshop,
      Taking Action Against Cardiovascular Disease in Our Communities: A Training for
      Service Providers, was a half-day workshop attended by 70 CHWs from various
      community service organizations. Approximately 97% of attendees said that the
      workshop met their expectations. More than half said they learned the signs and
      symptoms of cardiovascular disease and about 90% said that they received clear
      and concrete information that they could use with their clients. These
      evaluations also provided critiques regarding aspects of the workshop that could
      be improved upon and other information which will be used as a formative tool in
      developing future educational initiatives. In conclusion, this workshop
      demonstrated that it was feasible to develop effective community programs
      targeted at educating CHWs about cardiovascular disease.

PMID- 18058211
TI  - Genomics and the mechanism of P-glycoprotein (ABCB1).
AB  - The development of effective clinical interventions against multidrug resistance
      (MDR) in cancer remains a significant challenge. Single nucleotide polymorphisms
      (SNPs) contribute to wide variations in how individuals respond to medications
      and there are several SNPs in human P-glycoprotein (P-gp) that may influence the
      interactions of drug-substrates with the transporter. Interestingly, even some of
      the synonymous SNPs have functional consequences for P-gp. It is also becoming
      increasingly evident that an understanding of the transport pathway of P-gp may
      be necessary to design effective modulators. In this review we discuss: (1) The
      potential importance of SNPs (both synonymous and non-synonymous) in MDR and (2)
      How new concepts that have emerged from structural studies with isolated
      nucleotide binding domains of bacterial ABC transporters have prompted
      biochemical studies on P-gp, leading to a better understanding of the mechanism
      of P-gp mediated transport. Our results suggest that the power-stroke is provided
      only after formation of the pre-hydrolysis transition-like (E.S) state during ATP
      hydrolysis.

PMID- 18058212
TI  - Friendship in high-functioning children with autism spectrum disorder: mixed and
      non-mixed dyads.
AB  - Friendships containing a child with autism and a friend with typical development
      ("mixed" friendships, n = 26) and those of children with autism and a friend with
      a disability ("non-mixed," n = 16) were contrasted with friendships of typically
      developing subjects and their friends (n = 31). Measures included dyadic
      interaction samples, and interview and questionnaire data from subjects, friends,
      and parents. Mixed friendship interactions resembled typical friendships.
      Participants in mixed friendships were more responsive to one another, had
      stronger receptive language skills, exhibited greater positive social orientation
      and cohesion, and demonstrated more complex coordinated play than in the non
      mixed dyads. Exposure to typical peers appears to have significant effects on
      friendship behaviors.

PMID- 18058213
TI  - Performance of children and adolescents with Asperger syndrome or high
      functioning autism on advanced theory of mind tasks.
AB  - Although a number of advanced theory of mind tasks have been developed, there is
      a dearth of information on whether performances on different tasks are
      associated. The present study examined the performance of 21 children and
      adolescents with diagnoses of Asperger syndrome (AS) and 20 typically developing
      controls on three advanced theory of mind tasks: The Eyes Task, the Strange
      Stories, and the Stories from Everyday Life. The participants in the clinical
      group demonstrated lower performance than the controls on all the three tasks.
      The pattern of findings, however, indicates that these tasks may share different
      information-processing requirements in addition to tapping different mentalizing
      abilities.

PMID- 18058214
TI  - Children with autism: quality of life and parental concerns.
AB  - Past research has shown that children with autism and their families have
      compromised quality of life (QOL) in several domains. This study examined QOL and
      parental concerns in children with autism during early childhood, childhood, and
      adolescence compared to children with Attention Deficit Disorder/Attention
      Deficit Hyperactivity Disorder (ADD/ADHD) and to typical controls from a US
      national sample. Families with children diagnosed with autism reported more
      profound QOL effects than families of children with ADD/ADHD or unaffected
      controls. Children with autism were significantly less likely to attend religious
      services, more likely to miss school, and less likely to participate in organized
      activities. Parental concerns over learning difficulty, being bullied, stress
      coping, and achievement were overwhelming in the autism group relative to the
      comparison groups.

PMID- 18058215
TI  - Stability of the autism diagnostic interview-revised from pre-school to
      elementary school age in children with autism spectrum disorders.
AB  - This study examined the stability of scores on the ADI-R from pre-school to
      elementary school age in children with autism spectrum disorders (ASD).
      Participants were 35 children who, at T1, all had a clinical diagnosis of ASD. On
      initial assessment (mean age 3.5 years; SD 0.6 years), all met ADI-R algorithm
      criteria for autism. ADI-R assessments were repeated at follow up (FU; mean age
      10.5 years; SD 0.8 years). Changes in ADI-R total, domain and ADI-R algorithm
      item scores were assessed. Twenty-eight children continued to score above the ADI
      R cut-off for autism at FU, although significant decreases in ADI-R domain and
      item scores were also found. In conclusion while classification of children
      according to ADI-R criteria generally remained stable between pre-school and
      elementary school age, many children demonstrated significant improvements in
      symptom severity.

PMID- 18058216
TI  - Reliability of the ADI-R: multiple examiners evaluate a single case.
AB  - The authors assessed the reliability of the Autism Diagnostic Interview (ADI-R).
      Seven Clinical Examiners evaluated a three and one half year old female toddler
      suspected of being on the Autism Spectrum. Examiners showed agreement levels of
      94-96% across all items, with weighted kappa (K(w)) between .80 and .88. They
      were in 100% agreement on 74% of the items; in excellent agreement on 6% of the
      items (93-96%, with K(w) between .78 and .85); in good agreement on 7% (89-90%,
      with K(w) between .62 and 0.68); and in fair agreement on 3% (82 - 84%, with K(w)
      between .40 and .47). For the remaining 10% of ADI-R items, examiners showed poor
      agreement (50-81% with K(w )between -.67 and .37).

PMID- 18058217
TI  - Castration differentially affects spatial working and reference memory in male
      rats.
AB  - A male advantage for spatial learning and memory tasks is well documented among
      humans and rodents. A possible physiological cause for this male advantage is
      activational effects of androgens among males. The spatial memory of eight
      castrated and eight sham-castrated adult male rats was compared using a working
      reference memory version of the eight-arm radial arm maze followed by a reference
      memory version of the Morris water maze. After maze testing, blood was collected
      from each rat, and testosterone levels were determined using radioimmunoassay. In
      the radial arm maze, castrates committed significantly more working memory errors
      and significantly fewer reference memory errors than did shams. In the water
      maze, no statistically significant differences were found for acquisition or
      retention. There was a trend for shams with higher testosterone levels to have
      better retention in the water maze, but this seemed to be due to higher levels of
      perseverance rather than better reference memory. Castration may have affected
      performance in the radial arm maze and not in the water maze because the radial
      arm maze was a more difficult task or because the water maze was aversively
      motivated while the radial arm maze was appetitively motivated. Our results
      indicate that androgens improve working memory and may impair reference memory,
      but the effects of androgens on reference memory seem to be task dependent.

PMID- 18058218
TI  - Spatial and frequency differences of neuromagnetic activities in processing
      concrete and abstract words.
AB  - This study investigated the neuromagnetic spatial and frequency differences
      between recognizing concrete and abstract words using a 275 channel whole head
      magnetoencephalography (MEG) system. The stimuli consisted of 100 concrete words
      and 100 abstract words which were presented visually and auditorily
      simultaneously. The data of 12 right-handed healthy subjects in six different
      frequency bands were analyzed with synthetic aperture magnetometry (SAM) which
      can identify the frequency-dependent volumetric distribution of the evoked
      magnetic field. Concrete and abstract words evoked a very similar neuromagnetic
      activation pattern in the primary visual and auditory cortices. However, concrete
      words evoked stronger synchronization in the right hemisphere and abstract words
      evoked stronger synchronization in the left hemisphere in 1-8 Hz. In addition,
      concrete words evoked more desynchronization in the left posterior temporal and
      parietal cortex; while abstract words evoked a clear synchronization in the left
      posterior temporal cortex and desynchronization in the left inferior frontal
      cortex in 70-120 Hz. Furthermore, concrete words evoked clear desynchronization
      in the left inferior frontal cortex while abstract words evoked strong
      synchronization in the left posterior temporal cortex in 200-300 Hz. These
      findings suggested that concrete words and abstract words are processed
      differently in the brain not only in anatomical substrates, but also in the
      frequency band of neural activation.

PMID- 18058219
TI  - Factors influencing consumer Outcome Monitoring in implementation of evidence
      based practices: results from the National EBP Implementation Project.
AB  - OBJECTIVE: This study reports participating agencies use of a single fidelity
      dimension, Outcome Monitoring, during the 2-year National EBP Implementation
      Project. METHOD: The study involved an emerging theme qualitative approach for
      analyzing the implementation of fidelity achieved for five EBPs in 49 sites
      across eight states. RESULTS: Twenty-seven percent of the sites reached a high
      level of implementation fidelity. CONCLUSION: Results suggest that four
      interrelated factors contributed to whether agencies successfully implemented
      Outcome Monitoring-agency data collection methods, agency culture, practitioner
      skill, and how well "consumer outcomes" are defined.

PMID- 18058220
TI  - Managing treatment resistant violent adolescents: a step forward by substituting
      seclusion for mechanical restraint?
AB  - Despite a growing consensus that seclusion or restraint should never be used with
      children or adolescents, there are a few patients who are resistant to treatment,
      and are persistently violent. The purpose of this study was to measure the
      efficacy of installing a padded seclusion room to decrease the use of mechanical
      restraints, a potentially more emotionally traumatic and dangerous intervention
      than seclusion. After padded room installation, the number of monthly mechanical
      restraint events per 1000 patient days decreased by 93.7%, from 21.2 to 1.3. A
      padded seclusion room may offer a safer, albeit a less than desirable alternative
      to mechanical restraint.

PMID- 18058221
TI  - Experimental study of low dose ultrashortwave promoting nerve regeneration after
      acellular nerve allografts repairing the sciatic nerve gap of rats.
AB  - OBJECTIVES: To observe the effect of ultrashortwave (USW) therapy on nerve
      regeneration after acellular nerve allografts(ANA) repairing the sciatic nerve
      gap of rats and discuss its acting mechanisms. METHODS: Sixteen Wistar rats
      weighing 180-220 g were randomly divided into four groups with four rats in each
      group: normal control group; acellular group (ANA, treated by hypotonic-chemical
      detergent, was applied for bridging a 10 mm-long sciatic nerve defect); USW group
      (After 24 h of ANA repairing the sciatic nerve gap, low dose USW was
      administrated for 7 min, once a day, 20 times a course of treatment, three
      courses of treatment in all); and autografts group. 12 weeks after operation, a
      series of examinations was performed, including electrophysiological methods, the
      restoring rate of tibialis anterior muscle wet weight, histopathological
      observation (myelinated nerve number, myelin sheath thickness, and axon
      diameter), vascular endothelial growth factor (VEGF) mRNA expression of spinal
      cord, and muscle at injury site, and analyzed statistically. RESULTS: Compared to
      acellular nerve allografts alone, USW therapy can increase nerve conductive
      velocity, the restoring rate of tibialis anterior muscle wet weight, myelinated
      nerve number, axon diameter, VEGF mRNA expression of spinal cord, and muscle at
      injury site, the difference is significant. There were no differences between USW
      group and autografts group except myelin sheath thickness. CONCLUSIONS: USW
      therapy can promote nerve axon regeneration and Schwann cells proliferation after
      ANA repairing the sciatic nerve gap of rats, the upregulation of VEGF mRNA
      expression of spinal cord and muscle may play an important role.

PMID- 18058222
TI  - Heart rate and treatment effect in children with disruptive behavior disorders.
AB  - OBJECTIVE: To examine whether children with disruptive behavior disorders (DBDs;
      hyperkinetic conduct disorder, conduct disorder, hyperkinetic disorder)
      characterized by low heart rate profit less from an intensive cognitive
      behavioral intervention aimed at reducing impulsive, oppositional and aggressive
      behavior problems. METHOD: Basal heart rate was studied in twenty-three children
      (aged 7-12 years) with DBD at the beginning of intervention comprising an
      intensive day-care treatment and parent training. The disruptive behavior of the
      child was assessed before treatment and after termination (12 weeks later).
      Therapy responders and non-responders were compared in regard to heart rate and
      other risk factors (cognitive functioning and socio-economic status). RESULTS:
      Statistical analyses yielded evidence for a significant reduction of disruptive
      problem behaviors (aggression, delinquency) that is more prominent in DBD
      children with high heart rate scores compared to patients with low heart rate
      scores. Heart rate was significantly lower in children who did not profit from
      therapy. A logistic regression analysis revealed that heart rate is a significant
      predictor for therapy success whereas other risk factors had no impact on therapy
      success. CONCLUSION: Further studies investigating biological and psychosocial
      predictors of treatment effectiveness are necessary. In addition, it might be
      helpful to consider different subtypes of aggressive behavior for selecting the
      best possible treatment options.

PMID- 18058223
TI  - Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer
      revealed distinct rare genetic alterations.
AB  - The CHEK2 gene mutations I157T (c.470T>C) and IVS2+1G>A affecting the forkhead
      associated domain (FHA) have been shown to increase the risk of breast cancer
      development in several populations. We analyzed the CHEK2 gene segment coding for
      FHA domain in 673 unselected breast cancer patients and 683 controls from the
      Czech Republic using the denaturant high-performance liquid chromatography. The
      found frequency of predominant FHA alteration I157T did not differ between breast
      cancer patients (19/673; 2.82%) and controls (17/683; 2.49%; P=0.71). Besides
      this mutation we characterized another nine alterations-six located within FHA
      coding sequence and three occurring in introns 1 or 2). Eight variants occurred
      once each in patients with breast cancer and two were present in controls. Three
      alterations found in breast cancer patients were novel missense variants (Y159H,
      T172A, and L174F) affecting highly conservative residues in FHA domain. Despite
      the lack of association of I157T mutation with breast cancer development in our
      population we deduced that the FHA domain is the subject of rare population
      specific alterations that might modify risk of various cancers.

PMID- 18058224
TI  - Microarray analysis of altered sphingolipid metabolism reveals prognostic
      significance of sphingosine kinase 1 in breast cancer.
AB  - Beside their structural role for the cell membrane the family of sphingolipids
      act as effector molecules in signal transduction with links to various aspects of
      cancer initiation, progression and treatment response. The "sphingolipid
      rheostat" balances between apoptosis inducing ceramid and growth promoting
      sphingosine-1-phosphate. We analyzed gene expression of 43 proteins from this
      pathway in different subtypes of breast cancer using microarray data of 1,269
      tumor samples (test set n=171; validation sets n=1098) and observed significant
      differences for several genes. Sphingosine kinase 1 (SPHK1), ceramide
      galactosyltransferase (UGT8), and Ganglioside GD3-Synthase (ST8SIA1) displayed
      higher expression among ER negative tumors. In contrast, glucosylceramidsynthase
      (GCS), dihydroceramidsynthases (LASS4, LASS 6) and acid ceramidase (ASAH1) were
      higher expressed in ER positive samples. Survival analysis revealed a worse
      outcome of patients with high SPHK1 expression. To avoid a confounding effect of
      the ER status we also restricted the analysis to 750 patients with ER positive
      tumors. Again a worse outcome was observed for tumors displaying high SPHK1
      expression. While 75.8+/-1.9% of the patients with tumors low in SPHK1 expression
      were free of metastasis at 5 years, this was the case for only 64.9+/-3.6% of
      patients with tumors displaying high SPHK1 expression (P=0.008).
      Immunohistochemistry identified the carcinoma cells as the major source of SPHK1
      expression in the tumor. The correlation of SPHK1 with a poor prognosis as well
      as its high expression among ER negative tumors are in line with the
      antiapoptotic and proliferative properties of its product sphingosine-1
      phosphate. Targeting of the sphingolipid rheostat may thus open new treatment
      options.

PMID- 18058225
TI  - Molecular epidemiologic features of inflammatory breast cancer: a comparison
      between Egyptian and US patients.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) is a lethal form of breast cancer
      with unknown etiology. A higher frequency of IBC and a more aggressive IBC
      phenotype was reported in Egypt than in the United States. This difference in
      disease frequency and presentation might be related to molecular epidemiologic
      factors. METHODS: We used tumor blocks and demographic, epidemiologic, and
      clinical data of 48 IBC patients from Egypt and 12 patients from the United
      States. We counted tumor emboli in tumors before and after immunohistochemical
      staining with lymphatic vessel endothelial receptor-1 (LYVE-1), and measured the
      expression of RhoC GTPase protein in the two groups. RESULTS: Erythema, edema,
      and peau d'orange were found in 77% of the Egyptian patients as compared with 29%
      found in the US patients (P=0.02). The number of tumor emboli was significantly
      higher in tumors from Egypt (mean+/-SD, 14.1+/-14.0) than in the tumors from the
      United States (5.0+/-4.0, P=0.01). The number of tumor emboli in LYVE-1 positive
      vessels was higher in tumors from Egypt (3.5+/-2.8) than tumors from the United
      States (1.6+/-0.5, P=0.15). We detected a high level of RhoC in 87% of the tumors
      from Egypt and 14% of the tumors from the United States (P=0.0003). CONCLUSION:
      Patients from Egypt have a more aggressive form of IBC than those in the United
      States. Our analysis of IBC patients shows that distinct molecular phenotypes can
      be found when these two study populations are compared. Future studies should
      explore the epidemiologic and environmental exposures and the genetic factors
      that might lead to the different clinical and molecular features of IBC in
      patients from these two countries.

PMID- 18058226
TI  - The RAD51D E233G variant and breast cancer risk: population-based and clinic
      based family studies of Australian women.
AB  - RAD51D is a homolog of the RAD51 protein, which is known to be an important
      component of the DNA repair pathway. A rare missense variant in the RAD51D gene,
      E233G (c.A>G), has been reported to be more prevalent in breast cancer cases from
      specific multiple-case breast cancer families, with an odds ratio of 2.6 (95%
      confidence interval (CI): 1.12-6.03). We assessed whether this variant was
      associated with breast cancer risk using two studies: a population-based case
      control-family study based on 1,110 cases and 629 controls, and a clinic-based
      study based on 390 cases from multiple-case breast cancer families. We conducted
      case-control analyses and modified segregation analyses of carrier families. The
      carrier frequencies (95% CI) of the RAD51D variant were 4.1% (2.4-6.6) for clinic
      based cases, 3.9% (2.8-5.2) for population-based cases, and 3.7% (2.3-5.4) for
      population-based controls, and were not significantly higher in case groups than
      controls (P=0.7 and P=0.8, respectively). After genotyping the relatives of cases
      who carried the variant, modified segregation analyses of these families were
      conducted, and the estimated hazard ratio for breast cancer corresponding to the
      E233G variant was 1.30 (95% CI: 0.66-2.58; P=0.4) for familial breast cancer
      families and 1.28 (95% CI: 0.47-3.43; P=0.6) for families unselected for family
      history. Therefore, despite being well powered to detect moderate risks, no
      evidence for an association between the E233G variant and breast cancer risk was
      observed in any setting. Larger studies would be required to determine if this
      variant is associated with a smaller risk of breast cancer.

PMID- 18058227
TI  - Breast cancer recurrence risk in relation to antidepressant use after diagnosis.
AB  - BACKGROUND: While laboratory data suggest that antidepressants may promote
      mammary tumor growth, there has been little research investigating whether
      antidepressant use after breast cancer diagnosis is associated with the risk of
      breast cancer recurrence. METHODS: We conducted a retrospective cohort study
      within Group Health, an integrated healthcare delivery system in Washington
      state. Women diagnosed with a first primary invasive, stage I, IIA, or IIB,
      unilateral breast carcinoma between 1990-1994 (aged>or=65 years) and 1996-1999
      (aged>or=18 years) were eligible for the study (N=1306). Recurrence within 5-year
      of diagnosis was ascertained by medical chart review. We used the pharmacy
      database to identify antidepressant dispensings from Group Health pharmacies. We
      used multiple Cox regression to estimate the hazard ratio for recurrence and
      breast cancer mortality, comparing users and non-users of antidepressant
      medications. Results for recurrence were examined separately in users and non
      users of tamoxifen. RESULTS: We did not observe an association between
      antidepressant use after breast cancer diagnosis and the risk of recurrence
      either in general (hazard ratio for any antidepressant use: 0.8; 95% confidence
      interval: 0.5-1.4) or for specific types of antidepressant medication. Risk of
      death from breast cancer did not differ between non-users and users of
      antidepressants. CONCLUSIONS: The results of this study suggest that women who
      use antidepressants after breast cancer diagnosis do not have an increased risk
      of recurrence or mortality.

PMID- 18058228
TI  - Prognostic factors in long-term breast cancer survivors with brain metastases.

PMID- 18058229
TI  - TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast
      cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response
      to neo-adjuvant chemo-radiotherapy.
AB  - The breast cancer incidence has been increasing in the south Indian women. A case
      (n=250)-control (n=500) study was undertaken to investigate the role of Single
      Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53
      (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in
      breast cancer. In addition, the value of the SNP's in predicting primary tumor's
      pathologic response following neo-adjuvant chemo-radiotherapy was assessed.
      Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay
      (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied
      were associated with a statistically significant increased risk for the breast
      cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and
      Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2
      fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate
      (P=0.003) analysis. There was no statistically significant association for the
      GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was
      found to predict complete pathologic response in the primary tumour following neo
      adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate
      analysis respectively) (P=0.004) and was independent of stage. This study
      suggests that SNP's can help predict breast cancer risk in south Indian women and
      that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary
      tumour.

PMID- 18058230
TI  - Beta-amyloid 25-35 peptide reduces the expression of glutamine transporter SAT1
      in cultured cortical neurons.
AB  - Beta-amyloid (Abeta) peptides may cause malfunction and death of neurons in
      Alzheimer's disease. We investigated the effect of Abeta on key transporters of
      amino acid neurotransmission in cells cultured from rat cerebral cortex. The
      cultures were treated with Abeta(25-35) at 3 and 10 microM for 12 and 24 h
      followed by quantitative analysis of immunofluorescence intensity. In mixed
      neuronal-glial cell cultures (from P1 rats), Abeta reduced the concentration of
      system A glutamine transporter 1 (SAT1), by up to 50% expressed relative to the
      neuronal marker microtubule-associated protein 2 (MAP2) in the same cell. No
      significant effects were detected on vesicular glutamate transporters VGLUT1 or
      VGLUT2 in neurons, or on glial system N glutamine transporter 1 (SN1). In
      neuronal cell cultures (from E18 rats), Abeta(25-35) did not reduce SAT1
      immunoreactivity, suggesting that the observed effect depends on the presence of
      astroglia. The results indicate that Abeta may impair neuronal function and
      transmitter synthesis, and perhaps reduce excitotoxicity, through a reduction in
      neuronal glutamine uptake.

PMID- 18058231
TI  - Estimation and interpretation of models of absolute risk from epidemiologic data,
      including family-based studies.
AB  - Absolute risk is the chance that a person with given risk factors and free of the
      disease of interest at age a will be diagnosed with that disease in the interval
      (a, a + tau]. Absolute risk is sometimes called cumulative incidence. Absolute
      risk is a "crude" risk because it is reduced by the chance that the person will
      die of competing causes of death before developing the disease of interest.
      Cohort studies admit flexibility in modeling absolute risk, either by allowing
      covariates to affect the cause-specific relative hazards or to affect the
      absolute risk itself. An advantage of cause-specific relative risk models is that
      various data sources can be used to fit the required components. For example,
      case-control data can be used to estimate relative risk and attributable risk,
      and these can be combined with registry data on age-specific composite hazard
      rates for the disease of interest and with national data on competing hazards of
      mortality to estimate absolute risk. Family-based designs, such as the kin-cohort
      design and collections of pedigrees with multiple affected individuals can be
      used to estimate the genotype-specific hazard of disease. Such analyses must be
      adjusted for ascertainment, and failure to take into account residual familial
      risk, such as might be induced by unmeasured genetic variants or by unmeasured
      behavioral or environmental exposures that are correlated within families, can
      lead to overestimates of mutation-specific absolute risk in the general
      population.

PMID- 18058232
TI  - Wedged hepatic venous pressure does not reflect portal pressure in patients with
      cirrhosis and hepatic veno-venous communications.
AB  - Some cirrhotic patients have hepatic veno-venous communications (HVVC) and large
      porto-systemic collaterals. However, the relationship between wedged hepatic vein
      pressure (WHVP) and portal vein pressure (PVP) in such patients is not clear. The
      aim of this study was to determine the relationships between simultaneously
      measured WHVP and PVP, and occluded hepatic and splenic portal venography in 100
      cirrhotic patients (40 alcoholic and 60 hepatitis C virus (HCV)-related
      cirrhosis). PVP and WHVP were closely related in both groups (alcoholic
      cirrhosis: 27.8 +/- 4.7 and 27.5 +/- 4.8 mmHg, HCV-cirrhosis: 27.3 +/- 3.7 and
      26.2 +/- 4.4 mmHg, respectively). Occluded hepatic venography revealed that 13 of
      the 100 patients had HVVC (alcoholic-cirrhosis: 4, HCV-cirrhosis: 9). In patients
      with HVVC, PVP (27.9 +/- 3.0 mmHg) was significantly higher than WHVP (21.9 +/-
      3.3 mmHg, P < 0.001). Large porto-systemic collaterals did not affect the
      relationship. We conclude that HVVC affects the relationship between PVP and
      WHVP. When WHVP is measured, occluded hepatic venography should be examined to
      detect HVVC.

PMID- 18058233
TI  - Suppression of ulcerative colitis in mice by orally available inhibitors of
      sphingosine kinase.
AB  - A critical step in the mechanism of action of inflammatory cytokines is the
      stimulation of sphingolipid metabolism, including activation of sphingosine
      kinase (SK), which produces the mitogenic and proinflammatory lipid sphingosine 1
      phosphate (S1P). We have developed orally bioavailable compounds that effectively
      inhibit SK activity in vitro in intact cells and in cancer models in vivo. In
      this study, we assessed the effects of these SK inhibitors on cellular responses
      to tumor necrosis factor alpha (TNFalpha) and evaluated their efficacy in the
      dextran sulfate sodium (DSS) model of ulcerative colitis in mice. Using several
      cell systems, it was shown that the SK inhibitors block the ability of TNFalpha
      to activate nuclear factor kappa B (NFkappaB), induce expression of adhesion
      proteins, and promote production of prostaglandin E(2) (PGE(2)). In an acute
      model of DSS-induced ulcerative colitis, SK inhibitors were equivalent to or more
      effective than Dipentum in reducing disease progression, colon shortening, and
      neutrophil infiltration into the colon. The effects of SK inhibitors were
      associated with decreased colonic levels of inflammatory cytokines TNFalpha,
      interleukin (IL)-1beta, interferon gamma (IFN)-gamma, IL-6, and reduction of S1P
      levels. A similar reduction in disease progression was provided by SK inhibitors
      in a chronic model of ulcerative colitis in which the mice received 3-week-long
      cycles of DSS interspaced with week-long recovery periods. In the chronic model,
      immunohistochemistry for SK showed increased expression in DSS-treated mice
      (compared with water-treated controls) that was reduced by drug treatment. S1P
      levels were also elevated in the DSS group and significantly reduced by drug
      treatment. Together, these data indicate that SK is a critical component in
      inflammation and that inhibitors of this enzyme may be useful in treating
      inflammatory bowel diseases.

PMID- 18058234
TI  - Community and team member factors that influence the early phase functioning of
      community prevention teams: the PROSPER project.
AB  - This research examines the early development of community teams in a specific
      university-community partnership project called PROSPER (Spoth et al., Prev Sci
      5:31-39, 2004). PROSPER supports local community teams in rural areas and small
      towns to implement evidence-based programs intended to support positive youth
      development and reduce early substance use. The study evaluated 14 community
      teams and included longitudinal data from 108 team members. Specifically, it
      examined how community demographics and team member characteristics, perceptions,
      and attitudes at initial team formation were related to local team functioning 6
      months later, when teams were planning for prevention program implementation.
      Findings indicate that community demographics (poverty), perceived community
      readiness, characteristics of local team members (previous collaborative
      experience) and attitudes toward prevention played a substantial role in
      predicting the quality of community team functioning 6 months later. EDITORS'
      STRATEGIC IMPLICATIONS: The authors identify barriers to successful long-term
      implementation of prevention programs and add to a small, but important,
      longitudinal research knowledge base related to community coalitions.

PMID- 18058235
TI  - The efficacy of a multicultural prevention intervention among urban American
      Indian youth in the southwest U.S.
AB  - This study explored how a non-targeted group of ethnic minority youth might or
      might not benefit from a prevention intervention focused on other cultural
      groups. The study specifically evaluated the effects of an evidence-based drug
      prevention curriculum with a sample of urban American Indian youth in the
      southwest U.S., most of whom self-reported multi-ethnic heritages. Using growth
      curve modeling, this research examined the developmental trajectory of drug use
      for these youth, and compared it with the trajectory of youth from other
      racial/ethnic groups at pre-intervention, post-intervention, and two follow up
      time periods. Results indicate that alcohol and marijuana use increased from pre
      intervention across subsequent time periods for all youth. The drug use of the
      American Indian youth in the treatment group increased on some measures.
      Specifically, they reported a steeper trajectory in the amount and frequency of
      alcohol and marijuana use compared to the youths in the treatment groups with
      other racial/ethnic identifications. The implications of these findings for the
      development of culturally grounded prevention programs for multi-ethnic, urban
      American Indian youth are discussed. EDITORS' STRATEGIC IMPLICATIONS: This
      research provides a specific example, but also makes a strong global argument,
      for the need to develop and evaluate prevention programs that are culturally
      grounded in the worldview of the target group.

PMID- 18058236
TI  - A molecular mechanism for mimosine-induced apoptosis involving oxidative stress
      and mitochondrial activation.
AB  - Mimosine, a non-protein amino acid, is mainly known for its action as a
      reversible inhibitor of DNA replication and, therefore, has been widely used as a
      cell cycle synchronizing agent. Recently, it has been shown that mimosine also
      induces apoptosis, as mainly reflected in its ability to elicit characteristic
      nuclear changes. The present study elucidates the mechanism underlying mimosine's
      apoptotic effects, using the U-937 leukemia cell line. We now demonstrate that in
      isolated rat liver mitochondria, mimosine induces mitochondrial swelling that can
      be inhibited by cyclosporine A, indicative of permeability transition (PT) mega
      channel opening. Mimosine-induced apoptosis was accompanied by formation of
      hydrogen peroxide and a decrease in reduced glutathione levels. The apoptotic
      process was partially inhibited by cyclosporine A and substantially blocked by
      the antioxidant N-acetylcysteine, suggesting an essential role for reactive
      oxygen species formation during the apoptotic processes. The apoptosis induced by
      mimosine was also accompanied by a decrease in mitochondrial membrane potential,
      cytochrome c release and caspase 3 and 9 activation. Our results thus imply that
      mimosine activates apoptosis through mitochondrial activation and formation of
      H2O2, both of which play functional roles in the induction of cell death.

PMID- 18058237
TI  - Expression of p16(INK4A) gene in human pituitary tumours.
AB  - Pituitary adenomas comprise 10-15% of primary intracranial tumours but the
      mechanisms leading to tumour development are yet to be clearly established. The
      retinoblastoma pathway, which regulates the progression through the cell cycle,
      is often deregulated in different types of tumours. We studied the cyclin
      dependent kinase inhibitor p16(INK4A) gene expression at mRNA level in human
      pituitary adenomas. Forty-six tumour specimens of different subtypes, 21
      clinically non-functioning, 12 growth hormone-secreting, 6 prolactin-secreting, 6
      adrenocorticotropin-secreting, and 1 thyrotropin-secreting tumours were studied.
      All clinically non-functioning and most of the hormone-secreting tumours were
      macroadenomas (38/46). The RT-PCR assay and electrophoresis of the PCR-products
      showed that p16(INK4A) mRNA was undetectable in: 62% of non-functioning, 8% of
      growth hormone-secreting, 17% of prolactin-secreting and 17% of
      adrenocorticotropin-secreting adenomas. Forty percent of all macroadenomas and
      25% of microadenomas had negative p16(INK4A) mRNA, the latter results suggest
      that the absence of p16(INK4A) product might be an early event in tumours with no
      expression of this suppressor gene. Within the non-functioning adenomas 63% were
      "null cell" and 37% were positive for some hormone, both subgroups showed similar
      percentage of cases with absence of p16(INK4A) mRNA. Our results show that
      clinically non-functioning macroadenomas have impaired p16(INK4A) expression in a
      clearly higher proportion than any other pituitary tumour subtype investigated.
      Other regulatory pathways may be implicated in the development of tumours with
      positive p16(INK4A) expression.

PMID- 18058238
TI  - Triple jeopardy in the pituitary.
AB  - Aggressive pituitary tumors are rare the pathogenesis is not well established.
      The development of pituitary tumor after apoplexy has also been rarely reported.
      We describe the sequential development of Cushing's disease, apoplexy and
      aggressive pituitary tumor in the same patient. A 31-year old male presented with
      eutopic ACTH dependent Cushing's syndrome which failed initial pituitary surgery.
      He underwent subsequent bilateral adrenalectomy for control of hypercortisolism.
      An episode of pituitary apoplexy then occurred which was followed by the
      development of a null-cell pituitary tumor. This second tumor exhibited an
      aggressive behavior with invasion into the surrounding structures and systemic
      spread clinically. This case provides important evidence for the hypotheses of
      the pathogenesis of aggressive pituitary tumors which could have arisen from
      surviving adenoma cells following apoplexy or as a de novo development of
      pituitary carcinoma from cells which were not part of the original adenoma. This
      is the first report of a transformation of Cushing's disease to an aggressive and
      invasive null cell tumor after pituitary irradiation, apoplexy and surgery.

PMID- 18058240
TI  - A knowledge-based approach to generating diverse but energetically representative
      ensembles of ligand conformers.
AB  - This paper describes a new and efficient stochastic conformational sampling
      method for generating a range of low-energy molecule conformations. Sampling can
      be tailored to a specific structural domain (e.g., peptides) by extracting
      torsional profiles from specific datasets and subsequently applying them to
      target molecules outside the reference set. The programs that handle creation of
      the knowledge-based torsional profiles and conformer generation per se are
      separate and so can be used independently or sequentially, depending on the task
      at hand. The conformational ensembles produced are contrasted with those
      generated using local minimization approaches. They are also quantitatively
      compared with a broader range of techniques in terms of speed and the ability to
      reproduce bound ligand conformations found in complexes with proteins.

PMID- 18058239
TI  - Functional magnetic resonance imaging of language in epilepsy.
AB  - Functional magnetic resonance imaging (fMRI) has revolutionized our understanding
      of functional networks and cerebral organization in both normal and pathological
      brains. In the present review, we describe the use of fMRI for mapping language
      in epilepsy patients prior to surgical intervention including a discussion of
      methodological issues and task design, comparisons between fMRI and the
      intracarotid sodium amobarbital test, fMRI studies of language reorganization,
      and the use of fMRI laterality indexes to predict outcome after anterior temporal
      lobectomy.

PMID- 18058242
TI  - The effect of numerical error on the reproducibility of molecular geometry
      optimizations.
AB  - Geometry optimization is one of the most often applied techniques in
      computational drug discovery. Although geometry optimization routines are
      generally deterministic, the minimization trajectories can be extremely sensitive
      to initial conditions, especially in case of larger systems such as proteins.
      Simple manipulations such as coordinate transformations (translations and
      rotations), file saving and retrieving, and hydrogen addition can introduce small
      variations ( approximately 0.001 A) in the starting coordinates which can
      drastically affect the minimization trajectory. With large systems, optimized
      geometry differences of up to 1 A RMSD and final energy differences of several
      kcal/mol can be observed when using many commercially available software
      packages. Differences in computer platforms can also lead to differences in
      minimization trajectories. Here we demonstrate how routine structure
      manipulations can introduce small variations in atomic coordinates, which upon
      geometry optimization, can give rise to unexpectedly large differences in
      optimized geometries and final energies. We also show how the same minimizations
      run on different computer platforms can also lead to different results. The
      implications of these findings on routine computational chemistry procedures are
      discussed.

PMID- 18058241
TI  - Molecular dynamics studies of alpha-helix stability in fibril-forming peptides.
AB  - Diseases associated with protein fibril-formation, such as the prion diseases and
      Alzheimer's disease, are gaining increased attention due to their medical
      importance and complex origins. Using molecular dynamics (MD) simulations in an
      aqueous environment, we have studied the stability of the alpha-helix covering
      positions 15-25 of the amyloid beta-peptide (A beta) involved in Alzheimer's
      disease. The effects of residue replacements, including the effects of A beta
      disease related mutations, were also investigated. The MD simulations show a very
      early (2 ns) loss of alpha-helical structure for the Flemish (A beta(A21G)),
      Italian (A beta(E22K)), and Iowa (A beta(D23N)) forms associated with hereditary
      Alzheimer's disease. Similarly, an early (5 ns) loss of alpha-helical structure
      was observed for the Dutch (A beta(E22Q)) variant. MD here provides a possible
      explanation for the structural changes. Two variants of A beta, A
      beta(K16A,L17A,F20A) and A beta(V18A,F19A,F20A), that do not produce fibrils in
      vitro were also investigated. The A beta(V18A,F19A,F20A) initially loses its
      helical conformation but refolds into helix several times and spends most of the
      simulation time in helical conformation. However, the A beta(K16A,L17A,F20A)
      loses the alpha-helical structure after 5 ns and does not refold. For the
      wildtype A beta(1-40) and A beta(1-42), the helical conformation is lost after 5
      ns or after 40 ns, respectively, while for the "familial" (A beta(A42T)) variant,
      the MD simulations suggest that a C-terminal beta-strand is stabilised, which
      could explain the fibrillation. The simulations for the Arctic (A beta(E22G))
      variant indicate that the alpha-helix is kept for 2 ns, but reappears 2 ns later,
      whereafter it disappears after 10 ns. The MD results are in several cases
      compatible with known experimental data, but the correlation is not perfect,
      indicating that multimerisation tendency and other factors might also be
      important for fibril formation.

PMID- 18058244
TI  - Differential staining and microchromosomal variation in karyotypes of four
      Brazilian species of Tupinambinae lizards (Squamata: Teiidae).
AB  - Kayotypes of four neotropical teiid lizard species (Tupinambinae) were herein
      studied after conventional as well as silver staining and CBG-banding:
      Crocodilurus amazonicus (2n = 34), Tupinambis teguixin (2n = 36), Tupinambis
      merianae and Tupinambis quadrilineatus (2n = 38). The karyological data for T.
      quadrilineatus as well as those obtained using differential staining for all
      species were unknown until now. The karyotypes of all species presented 12
      macrochromosomes identical in morphology, but differed in the number of
      microchromosomes: 22 in C. amazonicus, 24 in T. teguixin and 26 in T.
      quadrilineatus and T. merianae. The Ag-NOR located at the secondary constriction
      at the distal end of pair 2 is shared by all species, contrasting with the
      variability observed for this character in species of the related Teiinae. CBG
      banding revealed a species-specific pattern in T. quadrilineatus with conspicuous
      interstitial C-blocks at the proximal region of the long arm of pair 4 and the
      whole heterochromatic short arm of pair 6. The karyological data reported here
      corroborates the relationship hypothesis obtained for Tupinambis based on
      molecular characters. T. teguixin presents the putative ancestral karyotype for
      the genus with 2n = 36 whereas T. merianae and T. quadrilineatus exhibit 2n = 38,
      due to an additional pair of microchromosomes.

PMID- 18058243
TI  - Expression profiling of salinity-alkali stress responses by large-scale expressed
      sequence tag analysis in Tamarix hispid.
AB  - Tamarix hispida, a woody halophyte, thrives in saline and saline-alkali soil. To
      better understand the gene expression profiles that manifest in response to
      saline-alkali stress, three cDNA libraries were constructed from leaf tissue of
      T. hispida plants that were well watered and exposed to NaHCO3 for 24 and 52 h. A
      total of 9,447 high quality expressed sequence tags (ESTs) were obtained from the
      three libraries. These ESTs represent 3,945 unigenes, including 986 contigs and
      2,959 singlets. The numbers of unigenes obtained from the three libraries were
      1,752, 1,558 and 1,675, respectively. The EST analysis was performed to compare
      gene expression in the three cDNA libraries; the transcripts responsive to NaHCO3
      were identified. The differentially expressed transcripts were identified. The up
      regulation genes were involved in a variety function areas, such as stress
      related proteins, hormone signaling transduction, antioxidative response,
      transcriptional regulators, protein synthesis and destination, ion homeostasis,
      photosynthesis and metabolism. The results indicated that the response to NaHCO3
      in T. hispida is a complex one, involving multiple physiological and metabolic
      pathways. Nine gene expression patterns were compared in response to NaHCO3 and
      NaCl using real time reverse transcription-polymerase chain reaction (RT-PCR).
      Gene expression trends were similar after a 24-h exposure to either NaCl or
      NaHCO3, however, great variability was found after a 52-h exposure, indicating
      that short-term responses to either salt may not be obviously different.

PMID- 18058245
TI  - Histone deacetylases: target enzymes for cancer therapy.
AB  - Epigenic regulation of gene transcription has recently been the subject of a fast
      growing interest particularly in the field of cancer. Enzymatic acetylation and
      deacetylation of the epsilon-amino groups of lysine residues from nucleosomal
      histones, represents major molecular epigenic mechanisms controlling gene
      expression. Histone deacetylases (HDACs) and histone acetyl transferases (HAT)
      represent the two families of enzymes in charge of the control of the level of
      acetylation of the histone tails. By removing the acetyl groups that abrogate the
      positive charge of the lysine residues that maintain the histone tails attached
      to DNA, HDACs repress transcription. In mammals, these latter enzymes form three
      groups of related enzymes based on their sequence homology and are classified as
      HDACs I, II and III. Global inhibition of the HDACs I and II groups results in
      cell growth arrest and apoptosis of cancer cells and alters tumor growth in in
      vivo experimental models. Their surprisingly low general toxicity and their
      impressive efficiency in preclinical cancer models has led to consider HDAC
      inhibitors as very promising new anticancer pharmacological agents. In this
      review, we attempt to give a comprehensive overview of the role and the
      involvement of HDAC in carcinogenesis as well as the current progress on the
      development of HDAC general and specific inhibitors as new cancer therapies.

PMID- 18058247
TI  - Alcohol, marijuana, and tobacco use patterns among youth in Canada.
AB  - The authors characterized changes in the prevalence of alcohol, tobacco, and
      marijuana use over time, and examined age of onset, co-morbid use and
      sociodemographic factors associated with ever using alcohol, tobacco, or
      marijuana in a nationally representative sample of Canadian youth. Data were
      collected from students in grades 7-9 as part of the Canadian Youth Smoking
      Survey (n = 19,018 in 2002; n = 29,243 in 2004). Descriptive analyses examined
      age of onset, co-morbid substance use and changes over time. Logistic regression
      models were used to examine factors associated with ever trying alcohol, tobacco,
      or marijuana with the 2004 data. Alcohol was the most prevalent substance used by
      youth and it was also the only substance which exhibited increased rates of use
      between 2002 and 2004. Co-morbid substance use was common, and it was rare to
      find youth who had used marijuana or tobacco without also having tried alcohol.
      As expected, youth who had poorer school performance were more likely to drink
      and smoke marijuana or tobacco, as were youth with more disposable income. Such
      timely and relevant data are important for guiding future policy, programming,
      and surveillance activities.

PMID- 18058246
TI  - ASNM position statement: intraoperative monitoring of auditory evoked potentials.

PMID- 18058248
TI  - Analysis of lung cancer incidence in the Nurses' Health and the Health
      Professionals' Follow-Up Studies using a multistage carcinogenesis model.
AB  - We analyzed lung cancer incidence among non-smokers, continuing smokers, and ex
      smokers in the Nurses Health Study (NHS) and the Health Professionals Follow-Up
      Study (HPFS) using the two-stage clonal expansion (TSCE) model. Age-specific lung
      cancer incidence rates among non-smokers are identical in the two cohorts. Within
      the framework of the model, the main effect of cigarette smoke is on the
      promotion of partially altered cells on the pathway to cancer. Smoking-related
      promotion is somewhat higher among women, whereas smoking-related malignant
      conversion is somewhat lower. In both cohorts the relative risk for a given daily
      level of smoking is strongly modified by duration. Among smokers, the incidence
      in NHS relative to that in HPFS depends both on smoking intensity and duration.
      The age-adjusted risk is somewhat larger in NHS, but not significantly so. After
      smokers quit, the risk decreases over a period of many years and the temporal
      pattern of the decline is similar to that reported in other recent studies. Among
      ex-smokers, the incidence in NHS relative to that in HPFS depends both on
      previous levels of smoking and on time since quitting. The age-adjusted risk
      among ex-smokers is somewhat higher in NHS, possibly due to differences in the
      age-distribution between the two cohorts.

PMID- 18058249
TI  - Chromosomal evolution in tenrecs (Microgale and Oryzorictes, Tenrecidae) from the
      Central Highlands of Madagascar.
AB  - Tenrecs (Tenrecidae) are a widely diversified assemblage of small eutherian
      mammals that occur in Madagascar and Western and Central Africa. With the
      exception of a few early karyotypic descriptions based on conventional staining,
      nothing is known about the chromosomal evolution of this family. We present a
      detailed analysis of G-banded and molecularly defined chromosomes based on
      fluorescence in situ hybridization (FISH) that allows a comprehensive comparison
      between the karyotypes of 11 species of two closely related Malagasy genera,
      Microgale (10 species) and Oryzorictes (one species), of the subfamily
      Oryzorictinae. The karyotypes of Microgale taiva and M. parvula (2n = 32) were
      found to be identical to that of O. hova (2n = 32) most likely reflecting the
      ancestral karyotypes of both genera, as well as that of the Oryzorictinae.
      Parsimony analysis of chromosomal rearrangements that could have arisen following
      Whole Arm Reciprocal Translocations (WARTs) showed, however, that these are more
      likely to be the result of Robertsonian translocations. A single most
      parsimonious tree was obtained that provides strong support for three species
      associations within Microgale, all of which are consistent with previous
      molecular and morphological investigations. By expanding on a recently published
      molecular clock for the Tenrecidae we were able to place our findings in a
      temporal framework that shows strong chromosomal rate heterogeneity within the
      Oryzorictinae. We use these data to critically examine the possible role of
      chromosomal rearrangements in speciation within Microgale.

PMID- 18058250
TI  - Monitoring compared with paleolimnology: implications for the definition of
      reference condition in limed lakes in Sweden.
AB  - Surface water acidification was identified as a major environmental problem in
      the 1960s. Consequently, a liming program was launched in Sweden in the 1970s.
      The primary purpose of liming is to restore conditions that existed prior to
      acidification. To reach this goal, as well as achieve 'good status' (i.e. low
      levels of distortion resulting from human activity) in European freshwaters until
      2016 under the European Union Water Framework Directive, lake data are required
      to define reference conditions. Here, we compare data from chemical/biological
      monitoring of 12 limed lakes with results of paleolimnological investigations, to
      address questions of reference conditions, acidification, and restoration by
      liming. Using diatom-based lake-water pH inferences, we found clear evidence of
      acidification in only five of the 12 lakes, which had all originally been
      classified as acidified according to monitoring data. After liming, measured and
      diatom-inferred pH agree well in seven lakes. The sediment record of three of the
      five remaining lakes gave ambiguous results, presumably due to sediment mixing or
      low sediment accumulation rates. It is difficult to determine whether liming
      restored the lakes to a good status, especially as some of the lakes were not
      acidified during the twentieth century. In addition to acid deposition, other
      factors, such as natural lake and catchment ontogeny or human impact through
      agricultural activity, influence lake acidity. This study shows that monitoring
      series are usually too short to define reference conditions for lakes, and that
      paleolimnological studies are useful to set appropriate goals for restoration and
      for evaluation of counter measures.

PMID- 18058251
TI  - Sources and seasonal variation of PAHs in the sediments of drinking water
      reservoirs in Hong Kong and the Dongjiang River (China).
AB  - The main objective of this study was to investigate occurrence of polycyclic
      aromatic hydrocarbons (PAHs) in the sources of the drinking water supply of Hong
      Kong. The main emphasis was on the Dongjiang River in mainland China which is the
      major source, supplying 80% of the total consumption in Hong Kong (the remaining
      20% is obtained from rain water). Sediments were collected from four sites along
      the Dongjiang River and four reservoirs in Hong Kong during both the dry and wet
      weather seasons. The concentrations of total PAHs in the sediments ranged between
      36 and 539 microg/kg dry wt. The lower levels were detected at the upstream site
      on the Dongjiang River and at the reservoirs in Hong Kong (44-85 microg/kg dry
      wt), while the mid- and downstream sites on the Dongjiang River were more
      polluted (588-658 microg/kg dry wt). Examination of the PAH profiles revealed
      that the mid- and downstream sections of the Dongjiang River contained high
      percentages of 4,5,6-ring PAHs, similar to the amounts of atmospheric particulate
      matter and road dust collected during the dry weather season from the Pearl River
      Delta region as reported in the literature. Seasonal changes were revealed in the
      reservoirs of Hong Kong, with higher PAH levels in the wet weather season than in
      the dry weather season. For those reservoirs in Hong Kong that store water from
      the Dongjiang River, a distinct seasonal pattern was also observed, namely, that
      under dry weather season conditions the PAHs found in the sediments were
      primarily from petrogenic source, while under wet weather season conditions they
      were from pyrolytic sources. No such pattern was detected in the reservoirs which
      stored only rain water.

PMID- 18058252
TI  - Lead forms in urban turfgrass and forest soils as related to organic matter
      content and pH.
AB  - Soil pH may influence speciation and extractability of Pb, depending on type of
      vegetation in urban soil environments. We investigated the relationship between
      soil pH and Pb extractability at forest and turf grass sites in Baltimore,
      Maryland. Our two hypotheses were: (1) due to lower pH values in forest soils,
      more Pb will be in exchangeable forms in forested than in turfgrass soils and (2)
      due to the greater lability of exchangeable Pb in equilibrium with soil solution
      in forest soils, concentrations of this form will increase with depth more so
      than in the turfgrass soils, as related to organic matter content and pH. Soil
      samples were collected from three forested and three turfgrass sites to depths of
      20 cm. Lead forms were determined using a sequential extraction technique. Soils
      under turfgrass and forest vegetation differed in the extractability of soil Pb
      (P < 0.01) for the Mn(III, IV)- and Fe(III)(hydr) oxide fraction. A greater Pb
      concentration was bound to this fraction under turfgrass (211 mg kg(-1), 69% of
      total Pb) than forested soils (67 mg kg(-1), 61% of total Pb), perhaps due to
      soil pH differences of 5.9 and 5.0, respectively. In the forested soils, as depth
      increased, the ratio of exchangeable-to-total Pb increased and the ratio of
      organically bound Pb-to-total Pb decreased. The results suggest changes in pH and
      organic matter content with depth affect the extractability of Pb, and these soil
      properties are affected differentially by grass versus tree vegetation in the
      urban soils investigated.

PMID- 18058254
TI  - Production of biosurfactants and antibiotics by fluorescent pseudomonads isolated
      from a closed hydroponic system equipped with a slow filter.
AB  - The presence of antibiotic- and biosurfactant-producing strains of fluorescent
      pseudomonads in a closed hydroponic system equipped with a slow filter was
      investigated. A total of 271 strains of pseudomonads were isolated before the
      filter, from the filter skin and from the effluent. Production of biosurfactants
      was determined using the drop-collapse method. The ability of the strains to
      inhibit the growth of the plant pathogens Pythium ultimum, Phytophthora cryptogea
      and Fusarium oxysporum was determined using dual culture plating. The influence
      of carbon sources on production was determined for selected strains, which also
      were identified to species level. Production of antibiotics or biosurfactants was
      observed to be a common trait among the fluorescent pseudomonads within the
      closed hydroponic system and it was affected by the filter. Pythium ultimum was
      the pathogen that was most sensitive to antibiotics produced by the fluorescent
      pseudomonads. The results indicated a strong influence of nutritional resources
      on antibiotic and biosurfactant production.

PMID- 18058253
TI  - Environmental contaminants in male river otters from Oregon and Washington, USA,
      1994-1999.
AB  - This study reports hepatic concentrations and distribution patterns of select
      metals, organochlorine pesticides (OCs), polychlorinated biphenyls (PCBs),
      polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) in 180 male river otters (Lontra canadensis) collected from Oregon and
      Washington, 1994-1999. Seven regional locations of western Oregon and Washington
      were delineated based on associations with major population centers, industry or
      agriculture. Cadmium (Cd) was not found above 0.5 microg g(-1), dry weight (dw)
      in juveniles, but increased with age in adults though concentrations were
      generally low (nd-1.18 microg g(-1), dw). Regional geometric means for total
      mercury (THg) ranged from 3.63 to 8.05 microg g(-1), dw in juveniles and 3.46
      12.6 microg g(-1) (dw) in adults. The highest THg concentration was 148 microg g(
      1), dw from an apparently healthy adult male from the Olympic Peninsula of
      Washington. Although THg increased with age in adult otters, the occurrence of
      the more toxic form methylmercury (MeHg) was not evaluated. Mean OC and PCB
      concentrations reported in this study declined dramatically from those reported
      in 1978-1979 from the lower Columbia River. Organochlorine pesticide and
      metabolite means for both juvenile and adult river otter males were all below 100
      microg kg(-1), wet weight (ww), with only DDE, DDD and HCB having individual
      concentrations exceeding 500 microg kg(-1), ww. Mean SigmaPCB concentrations in
      both juvenile and adult male otters were below 1 microg g(-1) for all regional
      locations. Mean juvenile and adult concentrations of non-ortho substituted PCBs,
      PCDDs and PCDFs were in the low ng kg(-1) for all locations studied.

PMID- 18058255
TI  - Inhibition on Hepatitis B virus in vitro of recombinant MAP30 from bitter melon.
AB  - The gene encoding MAP30 protein was cloned from bitter melon and recombinant
      MAP30 was expressed and purified. The human hepatoma G2.2.15 cells were exposed
      to different concentrations of MAP30. MTT assay was used to evaluate the
      cytotoxicity of the drugs and real-time PCR and Southern hybridization were
      applied to quantify extracellular HBV DNA and replicative intermediates
      intracellular and cccDNA in nucleus. HBsAg and HBeAg were assessed by enzyme
      linked immunosorbent assay (ELISA). The results showed that exposure of
      HepG2.2.15 cells to MAP30 resulted in inhibition of HBV DNA replication and HBsAg
      secretion. After exposed to three different concentrations of MAP30 for 2, 4, 6,
      and 8 days respectively, the inhibition rates of extracellular HBV DNA, HBsAg,
      and HBeAg of each concentration decreased significantly (P < 0.05). After 9 days
      of treatment, the inhibition rates of extracellular HBV DNA of the different
      concentrations differed greatly (P < 0.001). The MAP30 could inhibit the
      production of HBV (P < 0.01) dose-dependently. The expression of HBsAg was
      significantly decreased by MAP30 dose-dependently (P < 0.001) and time
      dependently (P < 0.001). Lower dose of MAP30 (8.0 microg/ml) could inhibit the
      expression of HBsAg and HBeAg.

PMID- 18058256
TI  - Pupillary reactivity upon hospital admission predicts long-term outcome in poor
      grade aneurysmal subarachnoid hemorrhage patients.
AB  - BACKGROUND: Historically, the prognosis for poor grade subarachnoid hemorrhage
      patients has been considered dismal. As a result, many hospitals have chosen
      conservative management over aggressive therapy. This guarded approach, however,
      is based on studies that do not take into account newer, more effective,
      management protocols and more recent long-term evidence that significant
      neurological recovery occurs in the months to years following discharge. More
      accurate and predictive methods are needed to decide when aggressive therapy is
      warranted. METHODS: Two hundred and twenty-six grade aneurysmal subarachnoid
      hemorrhage (aSAH) patients of grades IV and V were admitted to Columbia
      University Medical Center and enrolled in our study. Demographics, clinical
      information (e.g. pupillary reactivity on admission), and treatment course
      (operative versus non-operative) were recorded. Rankin scores at 14 days, 3
      months, and 1 year were also recorded. A favorable Rankin score was defined as 0
      3. Unfavorable was defined as 4-6. RESULTS: Among all poor grade patients who
      received operative therapy, pupillary reactivity at admission was not predictive
      of a favorable Rankin score at day 14 (odds ratio = 3.3, P = 0.129). Pupillary
      reactivity, however, was predictive of Rankin score at 3 months (odds ratio =
      4.57, P = 0.05) and 12 months (odds ratio = 6.44, P = 0.008). After constructing
      a Kaplan-Meiers survival curve, pupillary reactivity was a better predictor of
      survival at 12 months than H&H grade [Hazard ratio 3.342 (1.596-7.000) P = 0.001
      versus 1.964 (1.016-3.798) P = 0.045]. CONCLUSIONS: This study demonstrates that
      significant recovery occurs in the weeks to months after poor grade aSAH.
      Pupillary reactivity on admission can be used as a predictor of survival and
      recovery at intermediate and long-term time points, more so than Hunt and Hess
      grade.

PMID- 18058258
TI  - Autoimmunity to type VII collagen: epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is an acquired, autoimmune, mechanobullous
      disease with clinical features reminiscent of genetic dystrophic epidermolysis
      bullosa (DEB). EBA patients have skin fragility, blisters, scars, and milia
      formation. DEB is due to a genetic defect in the gene-encoding type VII collagen,
      which makes anchoring fibrils, structures that attach the epidermis and its
      underlying basement membrane zone onto the papillary dermis. DEB patients have a
      decrease in normally functioning anchoring fibrils. EBA patients have the same
      problem, but their decrease in normally functioning anchoring fibrils is because
      of an abnormality in their immune system in which they produce anti-type VII
      collagen antibodies that attack their anchoring fibrils. These IgG anti-type VII
      collagen antibodies are "pathogenic" because when injected into a mouse, the
      mouse develops an EBA-like blistering disease. EBA has several distinct clinical
      presentations. It can present with features similar to DEB. It can also present
      with features reminiscent of bullous pemphigoid, cicatricial pemphigoid,
      Brunsting-Perry pemphigoid, or IgA bullous dermatosis. Treatment for EBA is
      unsatisfactory. Some therapeutic success has been reported with colchichine,
      dapsone, photopheresis, infliximab, and IVIG.

PMID- 18058259
TI  - Retinol binding protein 4, low birth weight-related insulin resistance and
      hormonal contraception.
AB  - It has been recently reported that increased serum levels of retinol binding
      protein 4 (RBP4), a molecule secreted by adipocytes and liver, could be an early
      marker of insulin resistance (IR). We determined whether serum RBP4 was increased
      in low birth weight (LBW)-young women as a model of early-onset IR, through a
      historical prospective study. The study-population included 35 LBW and 35 born at
      term appropriate for gestational age (term AGA) young women. Metabolic
      evaluations included the composite-insulin sensitivity index (composite ISI).
      Serum RBP4 was measured with a competitive enzyme-linked immunosorbent assay
      (ELISA). RBP4 levels were similar in LBW and term AGA women, while composite ISI
      was significantly lower in the former group. With multivariate logistic
      regression analysis hormonal contraception (HC) use but not birth weight,
      diabetes in either parents and body mass index was significantly associated with
      higher RBP4 levels: odds ratio = 10.6; 95% confidence interval (CI) = 2.4-76.6.
      In spite of higher RBP4 levels in women under HC, composite ISI was similar in
      women with or without HC. Women under HC also exhibited significantly higher
      levels of sex hormone binding globulin (SHBG), triglycerides, cholesterol, and C
      reactive protein (CRP), and all of them, but not composite ISI, were
      significantly correlated with RBP4 levels. In conclusion, RBP4 serum level was
      not a marker of IR but, for the first time, it is documented a sustained increase
      of serum RBP4 under HC. Pathophysiological and clinical significance of this
      novel finding requires further investigations.

PMID- 18058257
TI  - Preclinical models of intracerebral hemorrhage: a translational perspective.
AB  - Intracerebral hemorrhage (ICH) is a devastating and relatively common disease
      affecting as many as 50,000 people annually in the United States alone. ICH
      remains associated with poor outcome, and approximately 40-50% of afflicted
      patients will die within 30 days. In reports from the NIH and AHA, the importance
      of developing clinically relevant models of ICH that will extend our
      understanding of the pathophysiology of the disease and target new therapeutic
      approaches was emphasized. Traditionally, preclinical ICH research has most
      commonly utilized two paradigms: clostridial collagenase-induced hemorrhage and
      autologous blood injection. In this article, the use of various species is
      examined in the context of the different model types for ICH, and a mechanistic
      approach is considered in evaluating the numerous breakthroughs in our current
      fund of knowledge. Each of the model types has its inherent strengths and
      weaknesses and has the potential to further our understanding of the
      pathophysiology and treatment of ICH. In particular, transgenic rodent models may
      be helpful in addressing genetic influences on recovery from ICH.

PMID- 18058260
TI  - Lack of association between interleukin-4 gene polymorphisms and autoimmune
      thyroid diseases amongst Taiwanese Chinese.
AB  - Graves' disease (GD) and Hashimoto's thyroiditis (HT) are both common autoimmune
      diseases of the thyroid gland (AITD). The IL-4 is involved in both humoral and
      cellular immunity. The aim of this study was to test whether the IL-4 gene could
      be used as a genetic marker to predict the development of AITD amongst the
      Chinese population of Taiwan. For this study, a normal control group of 105
      healthy subjects and two experimental groups featuring individuals afflicted with
      either GD (104 patients) or HT (109 patients) were examined. Polymerase chain
      reaction (PCR) was used to analyze the variable number of tandem repeats (VNTRs)
      polymorphism for the IL-4 gene intron 3 and PCR-based restriction analysis using
      endonuclease BsmFI was undertaken for the same gene at the promoter -590
      position. We found no significant difference in the frequencies of presence of
      genotype and allelic variants for the IL-4 gene at both the intron 3 and the
      promoter regions between the normal control group and each of the two patient
      groups. These findings suggest that the IL-4 gene polymorphisms that arise at
      either intron 3 or promoter -590 positions are not suitable genetic markers for
      AITD among Taiwanese Chinese.

PMID- 18058261
TI  - The genome browser at UCSC for locating genes, and much more!
AB  - For beginners in the field, this review highlights the key features of the genome
      browser at UCSC for data display, and provides nearly step-by-step procedures for
      creating publication quality maps. The browser offers an engine (Blat) for
      searching a known genomic DNA for correspondence with protein and DNA sequences
      specified by the user. The results provide links to graphical displays, known as
      maps. Users can create "designer maps" by adding Tracks to view various types of
      data and specific landmarks. The browser offers an extensive list of options.
      They include the position of annotated genes, the position of reference cDNA
      sequences (RefSeq from GenBank), the position of alternatively spliced mRNA
      species, and predictions derived from computational models to identify potential
      transcription start sites and potential protein binding elements in genomic DNA.
      Several tracks can be tailored for comparative genomics. The browser also offers
      tracks for displaying large-scale experimental data including gene expression
      profiles, exon chips, and single-nucleotide-polymorphisms.

PMID- 18058262
TI  - Gl-NETs-uniform but also diverse.
AB  - In the 100 years since the term Karzinoid was first coined by Siegfried
      Oberndorfer to describe gastrointestinal tumors that resembled carcinomas but
      pursued a relatively indolent course, these tumors have captured the attention,
      not only of internists, surgeons, endocrinologists, and pathologists but of
      biochemists, physiologists, geneticists, and molecular biologists as well.
      Initially thought to be limited to the gut, these tumors were soon found to arise
      in a variety of other organs as well. With the gradual evolution of the concept
      of a dispersed neuroendocrine cell system and the recognition that it was made up
      of a galaxy of at least 20 or so functionally distinct cell types (each of which
      could potentially give rise to a specific type of tumor, each of which could in
      turn be endocrinologically functional or silent), came the realization that
      carcinoids should perhaps be considered as a family of neoplasms that, despite
      sharing certain commonalities, can however, show significant heterogeneity among
      themselves in some of their other features. While it may seem that our knowledge
      of this fascinating group of tumors has improved significantly, a closer look
      reveals that we may have just begun to scratch the surface.

PMID- 18058263
TI  - Prognostic factors in gastrointestinal endocrine tumors.
AB  - The gastrointestinal endocrine tumors are neoplastic lesions with often elusive
      malignant clinical behavior. The current WHO classification attempted to define a
      more effective approach by introducing the concepts of cell differentiation and
      site-specific malignancy, as well as specific criteria for carcinoma definition.
      WHO clinicopathological correlations embed the prognostic features: degree of
      cell differentiation, angioinvasion, proliferation fraction as assessed by
      mitotic index and Ki67, size, and functional activity. Other prognostic variables
      have been recognized, most of which related to specific biological features of
      neuroendocrine cancer cells. Nonetheless, the presence of liver or distant
      metastases are the prognostic variables ultimately determining the patients' fate
      in terms of survival and/or therapy response. A recent proposal of tumor grading
      and tumor, nodes, and metastases (TNM) staging aims at a simple and practical
      system for patients stratification. Application of such proposal should be
      implemented in routine clinical practice.

PMID- 18058264
TI  - Endocrine precursor lesions of gastroenteropancreatic neuroendocrine tumors.
AB  - This review focuses on precursor lesions of gastrointestinal and pancreatic
      neuroendocrine tumors (GEP-NETs). There are three conditions that are associated
      with hyperplastic changes in endocrine cells preceding GEP-NETs: autoimmune
      chronic atrophic gastritis or multiple endocrine neoplasia type 1 (MEN1) with
      gastric enterochromaffin-like (ECL) cell hyperplasia; MEN1 with gastrin and
      somatostatin cell hyperplasia in the duodenum and glucagon cell hyperplasia in
      the islets of the pancreas; and inflammatory bowel disease with endocrine cell
      hyperplasia in the colon. In gastric ECL cell hyperplasia, it is assumed that
      hypergastrinemia promotes the growth of the ECL cells of the corpus mucosa and
      leads to hyperplasia and neoplasia. In the duodenum and the pancreas, the MEN1
      associated germline mutation of the menin gene obviously causes hyperplasia of
      the gastrin and somatostatin cells (duodenum) and the glucagon cells (pancreas),
      resulting in multifocal development of tumors. These tumors show allelic deletion
      of the MEN1 gene, whereas the precursor lesions retain their heterozygosity. The
      endocrine cell hyperplasia in the colon described in inflammatory bowel disease
      has neither a genetic nor a definite hormonal background.

PMID- 18058265
TI  - Differential expression of miRNAs in papillary thyroid carcinoma compared to
      multinodular goiter using formalin fixed paraffin embedded tissues.
AB  - microRNAs (miRNAs) are approximately 22 nt RNAs that negatively regulate target
      gene expression. Their dysregulation has been implicated in the pathogenesis of a
      number of human cancers, including papillary thyroid carcinoma (PTC). Whereas
      previous studies using microarray technologies have largely relied on the ability
      to procure fresh tissue at the time of surgery to characterize miRNA signatures
      in PTC, we exploited the ability to procure sufficient miRNA from formalin-fixed
      paraffin-embedded (FFPE) tissue to describe a series of miRNAs whose expression
      is dysregulated in PTC compared to benign proliferative multinodular goiter
      (MNG). We identified 13 miRNAs upregulated and 26 miRNAs downregulated in PTC
      versus MNG. These include miRNA-21, miRNA-31, miRNA-221, and miRNA-222. Their
      dysregulation was further validated by real time RT-PCR analysis in an
      independent set of FFPE tissues. Many of these have previously been described in
      fresh tissue studies as altered in PTC, confirming the utility of this approach.
      These results further highlight the applicability of miRNA expression patterns as
      potential markers of human cancer, and our results suggest that FFPE tissues are
      suitable resources for such miRNA expression analyses. The ability to utilize
      FFPE tissue in the molecular characterization of human malignancy will unlock a
      rich resource for future cancer studies.

PMID- 18058266
TI  - Somatotropes maintain their immature cells through Insulin-like growth factor I
      (IGF-I).
AB  - A pituitary tumor is considered to be composed of a heterogeneous population of
      hormone-producing endocrine cells, folliculo-stellate (FS) cells, and potential
      hormone-inactive progenitor cells to maintain a microenvironment such as that in
      angiogenesis for tumor development cooperatively. However, the system that
      maintains such a heterogeneous cell population has not been clarified yet. In the
      present study, we examined the mechanism for maintaining a heterogeneous cell
      population using two rat cell lines, MtT/S and MtT/E cells, which are known
      growth hormone (GH)-producing cells, and their progenitor cells, respectively. We
      found that conditioned medium of MtT/S cells could stimulate the growth of MtT/E
      cells. In addition, GH and insulin-like growth factor I (IGF-I) stimulated the
      growth of MtT/E cells. The messenger RNAs (mRNAs) of receptors for IGF-I and GH
      were expressed in the MtT/E cells. Moreover, IGF-I receptor inhibitor AG1024
      could abolish the growth stimulatory activity in the conditioned medium of MtT/S
      cells. Therefore, we concluded that somatotropes (MtT/S) maintain their
      progenitor cells (MtT/E) through the GH-IGF-I signaling and IGF-I directly, which
      might be involved in the maintenance of progenitors of GH-producing cells and
      might contribute to pituitary tumor development.

PMID- 18058267
TI  - Follicular variant papillary thyroid carcinoma arising in struma ovarii.
AB  - Struma ovarii is a rare monodermal ovarian teratoma in which thyroid tissue is
      the predominant or exclusive element. Malignant transformation is known to occur,
      usually as classical papillary thyroid carcinoma (PTC). However, the recognition
      of follicular variant PTC raises the possibility of similar malignancy arising in
      struma ovarii. We examined 13 cases of struma ovarii to determine if these
      lesions can exhibit histological, immunohistochemical, and/or molecular features
      of follicular variant PTC. Ten of these had atypical histology, cytologic
      features of PTC, and all ten showed diffuse positivity for CK19; eight of these
      were also positive for HMBE-1. Mutational analysis for BRAF identified no V600E
      mutations. However, seven of the ten cases with features of follicular variant
      PTC exhibited a rearranged in transformation (RET)/PTC rearrangement by reverse
      transcriptase polymerase chain reaction (RT-PCR). The three cases considered to
      be benign based on histologic and cytologic criteria were negative for CK19 and
      HBME-1 by immunohistochemistry, and had no evidence of BRAF mutation or ret/PTC-1
      and ret/PTC-3 rearrangements. These results indicate that follicular variant PTC
      can occur in struma ovarii and that such lesions exhibit the same morphologic and
      immunohistochemical profile as follicular variant PTC in thyroid. The application
      of molecular testing to verify the diagnosis can be valuable, as these lesions
      may harbor ret/PTC gene rearrangements.

PMID- 18058268
TI  - Functional oncocytic adrenocortical carcinoma.
AB  - We present a case of oncocytic adrenocortical carcinoma in a 25-year-old man who
      presented with persistent hypertension, hypokalemia, and a large right adrenal
      mass. Clinical workup revealed increased serum aldosterone level, suppressed
      serum ACTH level and high 24-h urine cortisol. Histologically the tumor showed
      several features of malignancy and electron microscopy confirmed oncocytic
      differentiation. This case is reported as the first case of an aldosterone and
      cortisol-producing malignancy with an oncocytic phenotype.

PMID- 18058273
TI  - Alcohol septal ablation for hypertrophic obstructive cardiomyopathy: focus on
      safety.

PMID- 18058274
TI  - Is alcohol ablation of the septum associated with recurrent tachyarrhythmias?
AB  - QUESTIONS UNDER STUDY: Alcohol ablation (AA) of the septum has been introduced as
      new therapy in hypertrophic cardiomyopathy (HCM). It was feared that iatrogenic
      myocardial infarction due to AA may induce re-entry tachyarrhythmias and increase
      sudden cardiac death. METHODS AND RESULTS: Twenty-four patients (mean age 52
      years) underwent successful AA. Clinical follow-up (FU) ranged from 0.3 to 0.7
      years (mean 2.8). One patient died (suicide) 4 years after AA. Left ventricular
      (LV) outflow gradient (peak-to-peak) decreased (median) after AA from 43 (IQR 25
      to 4) mmHg to 1 (IQR 0 to 12) mmHg (rest) (p <0.001) and from 130 (IQR 75 to 165)
      mmHg to 13 (IQR 0 to 31) mmHg (postextrasystolic) (p <0.001). Transient AV block
      occurred in 22% (5/24) necessitating temporary pacing. A permanent pacemaker was
      implanted in 4% (1/24). NYHA-class was 2.5 (IQR 2.0 to 3.0) before and 1.5 (IQR
      1.3 to 2.0) (p <0.001) after AA. During FU, 2 pacemakers were implanted due to
      bradycardia (no AV block). A right bundle branch block was found in 13% (2/24)
      before and 46 % (11/24) after AA (p = 0.003). Non-sustained ventricular
      tachycardia (NSVT) was observed in 13% (2/16) before and 22% (5/23) (p = 0.46)
      after AA. Two patients required ICD implantation. CONCLUSIONS: Long-term FU is
      excellent in HCM after AA. The pressure gradient drops below 25 mm Hg in 95%
      (23/24) of all patients. Transient AV block occurs in 22% (5/24), but permanent
      pacemaker implantation is rarely needed (13%, 2/24). Severe NSVT occurs in 13%
      (2/16) before and 22% (5/23) after AA but ICD implantation is only occasionally
      required.

PMID- 18058275
TI  - Efficacy and safety of universal valganciclovir prophylaxis combined with a
      tacrolimus/mycophenolate-based regimen in kidney transplantation.
AB  - BACKGROUND: Immunosuppressive and antiviral prophylactic drugs are needed to
      prevent acute rejection and infection after transplantation. We assessed the
      efficacy and safety of the introduction of universal valganciclovir prophylaxis
      in combination with a tacrolimus/mycophenolate-based regimen in kidney
      transplantation at our centre. METHODS: We reviewed all consecutive patients who
      underwent kidney transplantation over a 5.5-year period. Patients transplanted
      from January 2000 to March 2003 (period 1) were compared to patients from April
      2003 to July 2005 (period 2). In period 1 patients were treated with basiliximab,
      cyclosporine, steroids and mycophenolate (or azathioprine). Prophylaxis with
      valacyclovir was prescribed in cytomegalovirus (CMV) D+/R- patients, while any R+
      patients were managed with a preemptive approach. In period 2, immunosuppression
      consisted of basiliximab or thymoglobulin induction, tacrolimus, steroids and
      mycophenolate. Three-month CMV prophylaxis with valganciclovir was used in all at
      risk patients. RESULTS: Data analysis included 73 patients (period 1) and 70
      (period 2). Acute rejection was more frequent in period 1 than in period 2 (42%
      vs 7%, p <0.001). Overall, 30% of patients in period 1 were diagnosed with CMV
      infection/disease requiring antiviral treatment, compared with 11.4% in period 2
      (p = 0.003). Late-onset CMV disease remained a problem in D+/R- patients in both
      periods. There was no difference in incidence of BK virus nephropathy, fungal
      infections, PTLD, graft loss or mortality. However, 4 cases (5.7%) of delayed
      transient asymptomatic agranulocytosis were observed in period 2. CONCLUSIONS:
      The present analysis indicates that the combined regimen introduced in period 2
      improved clinical results with a significant decrease in acute rejection and in
      CMV infection/disease incidence. However, a unique syndrome of delayed transient
      agranulocytosis probably due to drug myelotoxicity was observed in a subset of
      patients.

PMID- 18058276
TI  - Missed appointments in an adolescent outpatient clinic: descriptive analyses of
      consultations over 8 years.
AB  - QUESTION UNDER STUDY: Missed appointments represent an important medical and
      economical issue. Few studies on the subject are reported in the literature,
      particularly regarding adolescents. Our aim was to characterize missed and
      cancelled appointments in a multidisciplinary outpatient clinic for adolescents,
      to assess the effectiveness of a policy aimed at reducing missed appointments by
      introducing payment for those missed appointments not cancelled in advance, and
      to compare the rates between staff and resident physicians. METHODS: A total of
      32,816 consultations (representing 35 patients aged 12-20 years, 82.4% females)
      between 1999 and 200 were analysed. RESULTS: The missed appointment rate was
      11.8% whilst another 10.9% were cancellations. Females cancelled more than males
      (11.3% vs. 8.4%, AOR 1.31, 99% CI 1.08-1.59), but there was no difference for
      missed appointments (11.6% vs. 12.3%, AOR 0.88, 99% CI 0.61-1.08). April and June
      to October (vacation months) were associated with more missed appointments.
      Globally mornings had higher rates of missed appointments than afternoons (13.6%
      vs. 11.2%, AOR 1.25, 99% CI 1.11-1.40). There was a slight difference in missed
      appointment rates between staff physicians and residents (10.4%; 11.8%, AOR 1.20,
      99% CI 1.08-1.33). Missed appointment rates before and after the new policy on
      missed appointments were similar (1999-2003: 11.9%; 2004-2006: 11.6%, AOR 0.96,
      99% CI 0.83-1.10). Conversely, cancellation rates increased from 8.4% (1999-2003)
      to 14.5% (2004-2006) (AOR 1.83, 99% CI 1.63-2.05). CONCLUSION: Attendance rates
      among adolescents show variations depending on vacation and school hours. Being
      attentive to these factors could help prevent missed appointments. Although
      having to pay for missed appointments does not increase attendance, it increases
      cancellations with the advantage that the appointment can be rescheduled.

PMID- 18058277
TI  - Radiosurgery for trigeminal neuralgia using a linear accelerator with BrainLab
      system: report on initial experience in Lausanne, Switzerland.
AB  - BACKGROUND/AIMS: Radiosurgery is an effective treatment for trigeminal neuralgia
      (TN) with minimal complications. Most experience is based on gamma knife
      radiosurgery (GKRS) and to a lesser extent on linear accelerators. METHODS: We
      report our initial experience in 17 patients with TN treated by an adapted linear
      accelerator using the BrainLab system. The trigeminal root entry zone immediately
      adjacent to the pons (target volume: 0.01-0.09 cm3, mean: 0.02 cm3) was targeted
      by use of a multileaf collimator to deliver 40-45 Gy to the 80% isodose (dose max
      50-56 Gy). Median follow-up was 12 months (range: 1-60). RESULTS: All patients
      reported some initial improvement in level of pain after treatment (mean time: 1
      month). Initial pain responses were as follows: 6 patients (35%) had complete
      pain relief and required no medication, 6 (35%) had occasional pain but were off
      medication, and 5 (30%) experienced partial relief of pain but still required
      medication, usually in lower doses. Five patients (29%) who experienced initial
      pain relief had recurrences ranging from 4-13 months after procedure. There were
      no major or minor complications of radiosurgery except one case of mild facial
      itching. CONCLUSION: Stereotactic radiosurgery using a linear accelerator appears
      to be effective and can be a favourable alternative to other procedures,
      including GKRS. The procedure is very safe and side effects are rare and minor.
      However, a randomised trial with a longer follow-up comparing radiosurgery to
      other surgical procedures is needed to assess the long term effectiveness of this
      treatment.

PMID- 18058278
TI  - Editorial: sharpening the focus in mood disorders: from disease models to
      individualized measurement-based care.

PMID- 18058279
TI  - Interpreting antidepressant clinical trials.
AB  - BACKGROUND: Psychiatrists and other clinicians make decisions about
      antidepressant medications with little understanding on how to interpret the
      research literature. METHODS: Pertinent clinical literature is reviewed. RESULTS:
      The author reviews levels of evidence, study design, statistical significance, p
      values, defining outcomes, drop outs, and basic analytic strategies such as last
      observation carried forward and mixed-effects model repeated measures. Several
      recent clinical trials are dissected to illustrate these concepts. CONCLUSIONS:
      Clinicians need to develop greater sophistication at interpreting research
      findings. No single study is definitive, and comparative antidepressant trials
      suffer from low statistical power.

PMID- 18058280
TI  - Managing depression in geriatric populations.
AB  - BACKGROUND: Late life depression is an increasingly acute public health concern
      due to the quickly expanding population of elderly in the US. The last few years
      has witnessed an explosion in the research literature changing our understanding
      of this disease. METHODS: Published studies over the past decade focusing on the
      epidemiology, phenomenology, comorbidity, and treatment of depression in the
      elderly were reviewed. RESULTS: The prevalence and phenomenology of depression in
      late-life varies with age. It remains highly prevalent in the elderly population,
      and certain vulnerable populations of older adults are at special risk. Further,
      the morbidity of late-life depression on physical health, social support systems,
      and overall functioning is considerable, making depression a leading cause of
      disability in elderly adults and a risk factor for mortality and suicide as well.
      Findings suggest a heterogeneity in etiology and in treatment response among
      older adults with depression, and differences from younger adults as well.
      CONCLUSIONS: This paper reviews our current understanding of late life depression
      and the implications for treatment and prevention. In addition, we review current
      research questions and future considerations in this field.

PMID- 18058281
TI  - Seasonal affective disorder: a clinical update.
AB  - BACKGROUND: Seasonal affective disorder (SAD) consists of recurrent major
      depressive episodes in the fall/winter with remissions in spring/summer. METHOD:
      A Medline search was conducted to identify studies relating to clinical
      management of SAD using the Medical Subject Heading, seasonal affective disorder,
      and key words, depress* and season*, focusing on studies published in the past 10
      years. The Cochrane library of systematic reviews was also searched for relevant
      studies. RESULTS: A careful history is important to make the diagnosis and
      differentiate SAD from other similar conditions such as subsyndromal SAD and
      atypical depression. Seasonal patterns with winter worsening are also recognized
      in "nonseasonal" depression as well as many other psychiatric conditions, and
      comorbidity with SAD is common. The pathophysiology of SAD seems to be
      heterogeneous as research on circadian, neurotransmitter function and genetic
      hypotheses have shown discrepant results. A dual vulnerability model with
      differential loading on separate seasonal and depression factors has been
      proposed to explain these findings. Recent systematic reviews have shown that
      light therapy is an efficacious and well-tolerated treatment for SAD. There is
      also evidence for efficacy of pharmacotherapy to treat and prevent SAD. Clinical
      studies show equal effectiveness with light and antidepressants, so patient
      preference should be considered in the selection of initial treatment. Dawn
      stimulation, negative air ions, exercise and cognitve behaviour therapy are under
      investigation and may also be helpful treatments for SAD. CONCLUSIONS: SAD is a
      common condition with significant psychosocial impairment. Clinicians should be
      vigilant in recognizing seasonal patterns of depressive episodes because there
      are effective, evidence-based treatments for SAD.

PMID- 18058282
TI  - Gender issues in depression.
AB  - BACKGROUND: Gender differences in depression have been documented for many years
      and thought to be insignificant to treatment selection until recently. METHODS:
      This article reviews gender differences in the prevalence, presentation,
      etiology, and antidepressant treatment of depressive disorders. RESULTS: The high
      female to male sex ratio in the prevalence of depression, especially during the
      reproductive years, is one of the most replicated findings in epidemiology. Women
      more often have a seasonal component, anxious and atypical depression.
      Explanations for the differences include psychological, neurochemical, anatomic,
      hormonal, genetic, and personality factors. Gender differences in antidepressant
      treatment response have not been found consistently. Hormonal status may be an
      important variable in addition to the effects of the menstrual cycle, pregnancy,
      perimenopause and menopause. CONCLUSIONS: Women have higher rates of depression
      and can often present differently than do men. Further research can ascertain
      which combination of factors increase women's risk. The effect of pregnancy and
      the impact of the menstrual cycle on the course of all depressive disorders need
      increased attention. Large prospective randomized controlled trials with gender
      differences in treatment response as the primary endpoint are necessary in order
      to answer the now controversial question of gender differences in antidepressant
      treatment response.

PMID- 18058283
TI  - Should Depressive Syndromes Be Reclassified as "Metabolic Syndrome Type II"?
AB  - BACKGROUND: A nascent explanatory theory regarding the pathophysiology of major
      depressive disorder posits that alterations in metabolic networks (e.g., insulin
      and glucocorticoid signaling) mediate allostasis. METHOD: We conducted a PubMed
      search of all English-language articles published between January 1966 and
      September 2006. The search terms were: neurobiology, cognition, neuroprotection,
      inflammation, oxidative stress, glucocorticoids, metabolic syndrome, diabetes
      mellitus, insulin, and antidiabetic agents, cross-referenced with the individual
      names of DSM-III-R/IV/-TR-defined mood disorders. The search was augmented with a
      manual review of article reference lists; articles selected for review were
      determined by author consensus. RESULTS: Disturbances in metabolic networks:
      e.g., insulin-glucose homeostasis, immuno-inflammatory processes, adipokine
      synthesis and secretion, intra-cellular signaling cascades, and mitochondrial
      respiration are implicated in the pathophysiology, brain volumetric changes,
      symptomatic expression (e.g., neurocognitive decline), and medical comorbidity in
      depressive disorders. The central nervous system, like the pancreas, is a
      critical modulator of the metabolic milieu and is endangered by chronic
      abnormalities in metabolic processes. We propose the notion of "metabolic
      syndrome type II" as a neuropsychiatric syndrome in which alterations in
      metabolic networks are a defining pathophysiological component. CONCLUSION: A
      comprehensive management approach for depressive disorders should routinely
      include opportunistic screening and primary prevention strategies targeting
      metabolically mediated comorbidity (e.g., cardiovascular disease). Innovative
      treatments for mood disorders, which primarily target aberrant metabolic
      networks, may constitute potentially novel, and disease-modifying, treatment
      avenues.

PMID- 18058284
TI  - Neuroimaging approaches in mood disorders: technique and clinical implications.
AB  - BACKGROUND: Clinical research in mood disorders increasingly involves advanced
      neuroimaging techniques. The encompassing aim of this review is to provide the
      mental health care practitioner with a pragmatic understanding of neuroimaging
      approaches and their possible clinical application. METHODS: We conducted a
      literature search of English-language articles using the search terms, major
      depressive disorder and bipolar disorder, cross-referenced with available
      neuroimaging technologies and analytical approaches, The search was supplemented
      with a manual review of relevant references. We organize the review by reviewing
      frequently asked questions on the topic of neuroimaging by mental health-care
      providers. RESULTS: Magnetic resonance (MR) approaches provide information on
      white and gray matter pathology (segmentation), cellular metabolism (MRS), oxygen
      consumption (BOLD), and neurocircuitry (DTI). Radionuclide-based neuroimaging
      methodologies provide quantitative estimates of brain glucose metabolism,
      regional blood flow, and ligand-receptor/transporter binding. Clinical
      implications of neuroimaging methodologies are reviewed. CONCLUSIONS: Advances in
      neuroimaging technology have refined models of disease pathophysiology in mood
      disorders and the mechanistic basis of antidepressant action. Multivariate
      analysis of functional and structural neuroimaging data, longitudinal analysis in
      the depressed and remitted states, and inclusion of representative patients with
      medical and psychiatric comorbidities will enhance the clinical translation of
      future research findings.

PMID- 18058285
TI  - Treatment resistant depression--advances in somatic therapies.
AB  - BACKGROUND: The failure to achieve remission for patients with Major Depressive
      Disorder (MDD) represents a major public health concern. Inadequately treated
      depression is associated with higher rates of relapse, poorer quality of life,
      deleterious personal and societal economic ramifications, as well as increased
      mortality rates. Unfortunately, only a minority of patients achieves this goal
      with initial antidepressant treatment and by convention, failure to achieve
      response after two adequate trials of antidepressant therapy defines "Treatment
      Resistant Depression" (TRD). Furthermore, results from the Sequenced Treatment
      Alternatives to Relieve Depression (STAR*D) group of studies suggest that
      approximately 50% of "real world" patients who meet criteria for MDD fail to
      achieve remission, even after four carefully monitored sequenced treatments.
      METHODS: Given these limitations of existing antidepressant medications alone and
      in combination, together with improved understanding of the neural circuitry of
      depression, it is not surprising that there is a renewed interest in
      neuromodulation strategies for TRD. RESULTS: The purpose of this article is to
      review the evidence for the inclusion of various non-pharmacological,
      neuromodulatory strategies for TRD. Specifically, information regarding the
      mechanism, tolerability and efficacy of electroconvulsive therapy (ECT), magnetic
      seizure therapy (MST), repetitive transcranial magnetic stimulation (rTMS), vagal
      nerve stimulation (VNS), and deep brain stimulation (DBS) in ameliorating TRD
      will be presented. CONCLUSIONS: Although these treatments are at various stages
      of clinical development, they represent a new frontier in expanding the treatment
      options available for individuals with TRD, as well as contributing to a better
      understanding the neurobiology of depressive disorders.

PMID- 18058286
TI  - Medical co-morbidity in depressive disorders.
AB  - BACKGROUND: Depression is much more prevalent among those with chronic medical
      conditions compared to the general population of the United States. Depression is
      recognized as a cause of increased morbidity and mortality and has been
      associated with higher health care costs, adverse health behaviors, significant
      functional impairment, lost work productivity, occupational disability and
      increased health care utilization. METHOD: Searches of Medline, OVIDMedline,
      PubMed and PsycINFO of all English-language articles published between 1966 and
      2007 were conducted using the keywords mood disorders, medical comorbidity,
      depression, antidepressant therapy. Supplemental references were manually
      extracted from relevant articles and chapters. Reviews of mechanistic studies and
      open label and randomized controlled trials of depression in patients with
      medical co morbidities were reviewed. RESULTS: Depressive disorders are prevalent
      among the medically ill and the relationship between depression and medical
      illness may be bidirectional. Antidepressant medications are effective in the
      treatment of depression in the medically ill. CONCLUSIONS: Depressive disorders
      can adversely impact the course of medical illnesses. Available antidepressant
      treatments are effective for the treatment of depression in the medically ill.
      Early identification and treatment of depression in medical illness can
      positively influence medical outcomes and quality of life.

PMID- 18058287
TI  - Differentiating bipolar disorders from major depressive disorders: treatment
      implications.
AB  - BACKGROUND: Bipolar disorder is a highly prevalent mood disorder, frequently
      misdiagnosed as unipolar major depressive disorder. METHODS: In order to
      summarize the historical and clinical features that may distinguish bipolar
      disorder and major depressive disorder, a MedLine search was conducted of all
      English-language articles published between 1996 and 2006 using the key search
      terms bipolar disorder and manic-depression cross-referenced with major
      depressive disorder. RESULTS: Better methods for arriving at the correct
      diagnosis of bipolar disorder include a clinical history that evaluates symptoms
      beyond narrow DSM-IV criteria and the use of self-reported screening tools.
      Twenty-six separate features were identified that are believed to aid in the
      differentiation of bipolar disorder from unipolar major depressive disorder.
      CONCLUSIONS: It is estimated that as many as 1 in 5 depressed outpatients may
      have undeclared bipolar disorder. Recognition of bipolar disorder can be improved
      by increasing the clinical acumen of diagnosticians and through the use of
      screening tools.

PMID- 18058288
TI  - Comparing features of bipolar disorder to major depressive disorder in a tertiary
      mood disorders clinic.
AB  - BACKGROUND: We sought to describe features that distinguish individuals with
      bipolar disorder from major depressive disorder. METHODS: A retrospective chart
      review of adult outpatients (N = 1000) seeking evaluation and treatment was
      conducted at the Mood Disorders Psychopharmacology Unit (MDPU), University Health
      Network, University of Toronto between October 2002 and November 2005 was
      conducted. Sociodemographic parameters, illness-characteristics and therapeutic
      interventions were evaluated and compared. RESULTS: The MDPU referring diagnosis
      were major depressive disorder (52%), bipolar disorder (29%), and unspecified
      (19%). Of all individuals with a non-bipolar entry diagnosis (n = 699), 23% (n =
      159) were subsequently diagnosed with bipolar disorder (p < 0.001); the majority
      of whom (n = 117, 74%) received a non-bipolar I disorder diagnosis [e.g. bipolar
      II disorder (n = 71); bipolar NOS disorder (n = 46) (p < 0.001)]. Higher rates of
      unemployment/disability, previous depressive episodes, psychiatric
      hospitalization, comorbid hypertension, and lifetime substance use disorders, as
      well as an earlier age of illness-onset were more frequently endorsed by
      individuals with a diagnosis of bipolar disorder. Fifteen percent of individuals
      who were newly-diagnosed with bipolar disorder reported a history of
      antidepressant-associated mania. CONCLUSIONS: The majority of individuals with a
      newly-diagnosed bipolar disorder at this tertiary center have a non-bipolar I
      disorder (i.e., bipolar spectrum). Several indices of illness severity
      differentiate individuals with bipolar disorder from major depressive disorder.

PMID- 18058300
TI  - Barnacle reattachment: a tool for studying barnacle adhesion.
AB  - Standard approaches for measuring adhesion strength of fouling organisms use
      barnacles, tubeworms or oysters settled and grown in the field or laboratory, to
      a measurable size. These approaches suffer from the vagaries of larval supply,
      settlement behavior, predation, disturbance and environmental stress. Procedures
      for reattaching barnacles to experimental surfaces are reported. When procedures
      are followed, adhesion strength measurements on silicone substrata after 2 weeks
      are comparable to those obtained using standard methods. Hydrophilic surfaces
      require reattachment for 2-4 weeks. The adhesion strength of barnacles in
      reattachment assays was positively correlated to results obtained from field
      testing a series of experimental polysiloxane fouling-release coatings (r =
      0.89). The reattachment method allows for precise barnacle orientation, enabling
      the use of small surfaces and the potential for automation. The method enables
      down-selection of coatings from combinatorial approaches to manageable levels for
      definitive field testing. Reattachment can be used with coatings that combine
      antifouling and fouling-release technologies.

PMID- 18058301
TI  - Methylphenidate poisoning: an evidence-based consensus guideline for out-of
      hospital management.
AB  - A review of US poison center data for 2004 showed over 8,000 ingestions of
      methylphenidate. A guideline that determines the conditions for emergency
      department referral and prehospital care could potentially optimize patient
      outcome, avoid unnecessary emergency department visits, reduce health care costs,
      and reduce life disruption for patients and caregivers. An evidence-based expert
      consensus process was used to create the guideline. Relevant articles were
      abstracted by a trained physician researcher. The first draft of the guideline
      was created by the lead author. The entire panel discussed and refined the
      guideline before distribution to secondary reviewers for comment. The panel then
      made changes based on the secondary review comments. The objective of this
      guideline is to assist poison center personnel in the appropriate out-of-hospital
      triage and initial out-of-hospital management of patients with suspected
      ingestions of methylphenidate by 1) describing the process by which a specialist
      in poison information should evaluate an exposure to methylphenidate, 2)
      identifying the key decision elements in managing cases of methylphenidate
      ingestion, 3) providing clear and practical recommendations that reflect the
      current state of knowledge, and 4) identifying needs for research. This review
      focuses on the ingestion of more than a single therapeutic dose of
      methylphenidate and the effects of an overdose and is based on an assessment of
      current scientific and clinical information. The expert consensus panel
      recognizes that specific patient care decisions may be at variance with this
      guideline and are the prerogative of the patient and the health professionals
      providing care, considering all of the circumstances involved. This guideline
      does not substitute for clinical judgment. Recommendations are in chronological
      order of likely clinical use. The grade of recommendation is in parentheses. 1)
      All patients with suicidal intent, intentional abuse, or in cases in which a
      malicious intent is suspected (e.g., child abuse or neglect) should be referred
      to an emergency department (Grade D). 2) In patients without evidence of self
      harm, abuse, or malicious intent, poison center personnel should elicit
      additional information including the time of the ingestion, the precise dose
      ingested, and the presence of coingestants (Grade D). 3) Patients who are
      chronically taking a monoamine oxidase inhibitor and who have ingested any amount
      of methylphenidate require referral to an emergency department (Grade D). 4)
      Patients experiencing any changes in behavior other than mild stimulation or
      agitation should be referred to an emergency department. Examples of moderate to
      severe symptoms that warrant referral include moderate-to-severe agitation,
      hallucinations, abnormal muscle movements, headache, chest pain, loss of
      consciousness, or convulsions (Grade D). 5) For patients referred to an emergency
      department, transportation via ambulance should be considered based on several
      factors including the condition of the patient and the length of time it will
      take for the patient to arrive at the emergency department (Grade D). 6) If the
      patient has no symptoms, and more than 3 hours have elapsed between the time of
      ingestion and the call to the poison center, referral to an emergency department
      is not recommended (Grade D). 7) Patients with acute or acute-on-chronic
      ingestions of less than a toxic dose (see recommendations 8, 9, and 10) or
      chronic exposures to methylphenidate with no or mild symptoms can be observed at
      home with instructions to call the poison center back if symptoms develop or
      worsen. For acute-on-chronic ingestions, the caller should be instructed not to
      administer methylphenidate to the patient for the next 24 hours. The poison
      center should consider making a follow-up call at approximately 3 hours after
      ingestion (Grade D). 8) Patients who ingest more than 2 mg/kg or 60 mg, whichever
      is less, of an immediate-release formulation (or the equivalent amount of a
      modified-release formulation that has been chewed) should be referred to an
      emergency department (Grade C). 9) If a patch has been swallowed, consider the
      entire contents of the patch (not just the labeled dose of the patch) to have
      been ingested. Patients who ingest more than 2 mg/kg or 60 mg, whichever is less
      should be referred to an emergency department. If it is known that the patch has
      been chewed only briefly, and the patch remains intact, significant toxicity is
      unlikely and emergency department referral is not necessary (Grade D). 10)
      Patients who ingest more than 4 mg/kg or 120 mg, whichever is less, of an intact
      modified-release formulation should be referred to an emergency department (Grade
      D). 11) For oral exposures, do not induce emesis (Grade D). 12) Pre-hospital
      activated charcoal administration, if available, should only be carried out by
      health professionals and only if no contraindications are present. Do not delay
      transportation in order to administer activate charcoal (Grade D). 13)
      Benzodiazepines can be administered by EMS personnel if agitation, dystonia, or
      convulsions are present and if authorized by EMS medical direction expressed by
      written treatment protocol or policy or direct medical oversight (Grade C). 14)
      Standard advanced cardiac life support (ACLS) measures should be administered by
      EMS personnel if respiratory arrest, cardiac dysrhythmias, or cardiac arrest are
      present and if authorized by EMS medical direction expressed by written treatment
      protocol or policy or direct medical oversight (Grade C).

PMID- 18058302
TI  - Does irritation potency contribute to the skin sensitization potency of contact
      allergens?
AB  - Chemicals that possess the capacity to cause skin sensitization have long been
      recognized to be reactive (electrophilic) or at least the precursor of an
      electrophile. The chemical species (hapten) covalently bound to skin protein then
      forms the antigen to which the immune system responds, with sufficient exposure
      ultimately leading to skin sensitization. However, for this process to occur,
      many have also considered that in addition to haptenation of skin protein,
      secondary stimuli (danger signals) are also necessary. Such signals might
      reasonably be expected to derive from keratinocytes and/or Langerhans cells
      perturbed by the chemical sensitizer. Whether this disturbance comes from the
      haptenation process itself or from other properties of the chemical is unknown.
      We hypothesized that chemicals that were stronger sensitizers might appear so, in
      part, as a consequence not only of greater (pro)electrophilic reactivity, but
      also if they were more able to produce inflammatory (danger) signals. To assess
      this, the sensitizing potency of 55 chemicals in the local lymph node assay was
      compared with their ability to produce pro-inflammatory signal release, measured
      as a function of their relative skin irritancy in guinea pigs. A limited trend
      was demonstrated, consistent with the hypothesis, but indicating that either skin
      irritation is a poor measure of danger signals, or that such signals are perhaps
      no more than a necessary requirement for the acquisition of skin sensitization
      rather than a key determinant of the relative potency of a skin sensitizing
      chemical. In addition, it is possible that irritancy alone does not represent a
      complete surrogate marker for the ability of a chemical to produce danger signals
      relevant to the induction of skin sensitization.

PMID- 18058303
TI  - Comedogenicity in rabbit: some cosmetic ingredients/vehicles.
AB  - The rabbit external ear canal was used to define which chemicals caused comedone
      formation on topical application. Some of the tested ingredients are currently
      used in topically applied formulations. Certain raw materials have been shown to
      produce follicular hyperkeratosis in the rabbit ear assay. This study quantifies
      comedogenic potential of cosmetic materials, including: isopropyl palmitate,
      isopropyl myristate, butyl stearate, isopropyl isostearate, decyl oleate,
      isostearyl neopentanoate, isocetyl stearate, myristle myristate, cocoa butter,
      cetyl alcohol, paraffin, stearyl alcohol sodium lauryl sulfate (SLS), and
      petrolatum. The first nine were deemed positive. Factors aiding clinical
      relevance are listed.

PMID- 18058304
TI  - The local lymph node assay: current position in the regulatory classification of
      skin sensitizing chemicals.
AB  - The local lymph node assay (LLNA) is being used increasingly in the
      identification of skin sensitizing chemicals for regulatory purposes. In the
      context of new chemicals legislation (REACH) in Europe, it is the preferred
      assay. The rationale for this is that the LLNA quantitative and objective
      approach to skin sensitization testing allied with the important animal welfare
      benefits that the method offers. However, as with certain guinea pig
      sensitization tests before it, this increasing use also brings experience with an
      increasingly wide range of industrial and other chemicals where the outcome of
      the assay does not always necessarily meet with the expectations of those
      conducting it. Sometimes, the result appears to be a false negative, but rather
      more commonly, the complaint is that the chemical represents a false positive.
      Against this background we have here reviewed a number of instances where false
      positive and false negative results have been described and have sought to
      reconcile science with expectation. Based on these analyses, it is our conclusion
      that false positives and false negatives do occur in the LLNA, as they do with
      any other skin sensitization assay (and indeed with all tests used for hazard
      identification), and that this occurs for a number of reasons. We further
      conclude, however, that false positive results in the LLNA, as with the guinea
      pig maximization test, arise most commonly via failure to distinguish what is
      scientifically correct from that which is unpalatable. The consequences of this
      confusion are discussed in the article, particularly in relation to the need to
      integrate both potency measurement and risk assessments into classification and
      labelling schemes that aim to manage potential risks to human health.

PMID- 18058305
TI  - Comparative study of Unna's Boot and betamethasone cream in the treatment of
      sulfur mustard-related pruritus.
AB  - Pruritus, as a chronic lesion caused by sulfur mustard, is a common problem among
      chemical weapons veterans. Numerous treatments like antihistamines, local
      anesthetics, and corticosteroids have been prescribed in order to control
      pruritus in these patients, while long- term and widespread use of each one of
      them has its own restrictions. Nowadays different mixtures, including Unna's
      Boot, are being used. They are effective and have limited adverse effects. So in
      this study we compared this product with corticosteroids. In this double-blind
      randomized clinical trial in Baqyiatallah hospital, 90 veterans were included and
      randomly divided into three groups. Subjects of each group received one of the
      Betamethasone %1 cream, Unna's Boot cream, or placebo cream for three weeks. They
      used their medication on an itching area of body, one finger tip unit every
      night. To evaluate the drugs' efficacy we used pruritus score index and Visual
      Analysis Score index. From 90 patients, 75 patients completely used the
      medication and the other 15 subjects were excluded from the study. All three
      drugs caused significant decrease in both pruritus score and VAS (p < .001).
      Betamethasone and Unna's Boot were significantly more effective than placebo and
      despite more efficacy of betamethasone rather than Unna's Boot, they did not have
      any significant differences (p > .05). Pruritus is a chronic lesion in veterans
      that needs long-term conservation treatment. Regarding definite side effects of
      local long-term therapy with corticosteroids and nearly equal efficacy of Unna's
      Boot and betamethasone, Unna's Boot seems to be a better choice in controlling
      sulfur mustard-related pruritus compared with betamethason.

PMID- 18058306
TI  - Corneal epithelial testing strategies for safety evaluation of ophthalmic
      formulations.
AB  - The toxicity of an ophthalmic formulation was tested both in vivo and in vitro.
      Initial tests on transformed human corneal epithelial (HCE-T) cells in monolayer
      cultures resulted in adverse effects on cell morphology. The adverse effects were
      unexpected since the formulation caused no damage to the cornea in vivo. These
      results suggested HCE-T monolayers do not adequately model the intact corneal
      epithelium. Therefore, further in vitro studies were conducted to investigate
      reversibility of morphologic changes, proliferation, cell viability, and effects
      on corneal epithelial barrier function. These tests showed that the formulation
      had no adverse effects on cell viability and proliferation. Multilayered cultures
      of HCE-T cells at an air interface provide a morphologic and physiologic model
      more relevant to the in vivo cornea. This study demonstrates the importance of
      selecting appropriate models when conducting in vitro toxicity studies so that
      potentially effective ophthalmic formulations are not rejected based on false
      positive in vitro endpoints.

PMID- 18058307
TI  - Hormesis [biological effects of low-level exposure (B.E.L.L.E.)] and dermatology.
AB  - Hormesis is characterized by nonmonotonic dose response that is biphasic,
      displaying opposite effects at low and high doses. Its occurrence has been
      documented across a broad range of biological models and diverse types of
      exposure. The effects of hormesis at various points can be beneficial or
      detrimental, depending on the context in which they occur. Because hormesis
      appears to be a relatively common phenomenon in many areas, the objective of this
      review is to explore its occurrence related to dermatology and its public health
      and risk assessment implication. Hormesis appears to be a common phenomenon in
      dermatology. Better understanding of this phenomenon will likely lead to
      different strategies for risk assessment process employed in the fields of
      dermatologic toxicology and pharmacology. More focus should be redirect from
      looking only at adverse effects at high levels of exposure to characterizing the
      complex biological effects, both adverse and beneficial, at low levels of
      exposure. Low-dose toxicology and pharmacology will not only provide a
      significant research challenge but also should contribute to better methods for
      low-dose risk assessment for complex mixtures of chemical compounds. This
      refocusing from high- to low-dose effects will shift the focus in the field of
      toxicology from emphasizing on adverse effects into studying the biological
      effects of chemical compounds on living organisms, taking into account the
      realization that the ultimate biological effect of a chemical may vary with its
      dose, the endpoint, the target organ considered, the interaction with other cell
      types/systems, and/or the combined exposure with other chemicals. The skin, with
      its ready accessibility, and its own areas of non-invasive technology, should
      provide fertile options to not only understand skin, but further explore
      practical implications in human and animal. We believe that hormesis is a common
      phenomenon and should be given detailed consideration to its concept and its risk
      assessment implications, and how these may be incorporated into the experimental
      and regulatory processes in dermatology. The skin, with its unique
      characteristics, its accessibility, and the availability of non-invasive
      bioengineering and DNA microarray technology, will be a good candidate to extend
      the biology of hormesis.

PMID- 18058308
TI  - Structural characteristics of the aging skin: a review.
AB  - As life expectancy in industrialized countries increases, appropriate care of
      elderly skin looms as a dermatologic priority. Skin aging is a complex,
      multifactorial process whose baseline rate is genetically determined but that may
      be accelerated by environmental, mechanical, or socioeconomic factors. The
      intrinsic structural changes that occur with the aging of the skin increase skin
      fragility, decrease the ability of the skin to heal, increase risk for
      toxicological injuries, promote the development of various cutaneous disorders,
      and produce aesthetically undesirable effects like wrinkling and uneven
      pigmentation. As aged patients represent a larger segment of the population,
      increased attention to the problems of the aged skin, both cosmetic and beyond,
      will be necessary and should build on currently successful interventions to
      improve their quality of life.

PMID- 18058309
TI  - In vitro approaches to the identification and characterization of skin
      sensitizers.
AB  - Allergic contact dermatitis (ACD) is to a considerable extent a preventable
      disease. Limitation of ACD can be achieved by correct detection of skin
      sensitizers, characterization of potency, understanding of human skin exposure,
      and the application of adequate risk assessment and management strategies. A
      range of methods now exist that have been proven to be very accurate in terms of
      the predictive identification of chemicals that possess skin sensitizing
      properties. In addition, certain methods, notably the local lymph node assay
      (LLNA), also deliver valuable information of the relative potency of identified
      sensitizers. Great use can be made of this potency information in the application
      of quantitative risk assessments (although of course such assessments depend also
      on the availability of accurate data on human skin exposure). However, the
      challenge now to be faced is how to obtain the same quality of information on the
      potency of skin sensitizing chemicals using solely in vitro and in silico
      methods. With the forthcoming elimination of in vivo tests, the opportunities
      being exploited for in vitro test development focus on key elements of the
      sensitization process, such as peptide binding and dendritic cell activation.
      What has to then be addressed is how information from such in vitro assays is
      integrated, together with data on epidermal bioavailability, to deliver an
      assessment of the allergen potency.

PMID- 18058310
TI  - Guinea pig maximization test assessment of hydrocortisone and tixocortol
      pivalate.
AB  - The anti-inflammatory properties of topical corticosteroids are well documented;
      additionally, their sensitization potential is also known. We aimed to assess the
      relative sensitization potential of hydrocortisone and tixocortol pivalate in an
      animal assay as it relates to potential for sensitization in humans. Using the
      guinea pig maximization test (GPMT), animals were sensitized intradermally on d0,
      and again topically on d7. On d21 the animals were challenged topically with a
      closed patch for 24 h and readings were taken 24 h and 48 h post-challenge. A
      sham control group received the same induction and challenge applications
      excluding the test agent. Animals were subsequently rechallenged with open
      application; the tixocortol pivalate group was further retested at different test
      agent concentrations to determine threshold concentration that elicited response.
      Tixocortol pivalate resulted in sensitization rates of 42% (24 h) and 80% (48 h);
      hydrocortisone exhibited 0% (24 h) and 5% (48 h). Scores ranged from 0% (sham
      group) to 2.4 (48 h tixocortol pivalate). Open rechallenge also resulted in
      greater tixocortol pivalate sensitization rates compared to hydrocortisone, 82%
      verse 16% at 48 h, respectively. All tested concentrations of tixocortol pivalate
      induced sensitization, albeit at differing rates dependant on concentration and
      timepoint. We conclude that the GPMT remains largely for hazard identification,
      as it was originally designed, and requires further data sets regarding
      quantitative induction and elicitation for risk assessment of various compounds
      in clinical implications.

PMID- 18058311
TI  - Cell lines and transgenic mice expressing a matrix metalloproteinase-9 promoter
      driven reporter gene: potential for assay of ultraviolet light effects and light
      inhibiting compounds.
AB  - Acute and chronic exposure to ultraviolet (UV) wavelengths in sunlight can cause
      adverse reactions in exposed areas of the skin and corneas. UV exposure up
      regulates the synthesis of Matrix Metalloproteinses (MMPs) and evidence suggests
      these enzymes mediate tissue damage. Therefore MMP gene activity can serve as a
      surrogate marker for bioassays. In this study, we tested the possible utility for
      this purpose of two stably transfected cell lines (from mouse keratinocytes and
      rabbit epithelial-like corneal cells) and a transgenic mouse line (line 3445),
      each harboring a DNA construct containing a bacterial beta-galactosidase (LacZ)
      reporter gene driven by the rabbit MMP-9 transcriptional promoter. We observed
      only a weak 2-fold maximal induction of LacZ reporter gene expression in the
      mouse epidermal cell line after exposure to UV-B irradiation (5, 10, 40 mJ/cm2)
      and no significant expression of the reporter gene in the rabbit epithelial-like
      cell line. Similarly negative results were obtained when primary corneal
      epithelial cells from human and rabbit were exposed to different doses of UV-B
      irradiation and endogenous MMP-9 gene expression was assayed by zymography and
      immunoprecipitation analysis. In contrast, when skin from 3-day-old transgenic
      mouse line 3445 was exposed to UV-B and UV-A, a clear dose-dependent induction of
      the LacZ reporter gene occurred and the location of gene expression was dependent
      on the wave-length of irradiation. These results suggest that line 3445
      transgenic mice may serve as a useful tool to quantitatively and qualitatively
      assess the biological effects of UV light and the efficacy of therapeutic agents.

PMID- 18058312
TI  - Conjugates of unsaturated fatty acids with propylene glycol as potentially less
      irritant skin penetration enhancers.
AB  - Fatty acids (FA) are well known as efficient enhancers for transdermal delivery
      of drugs; however, their frequent dermal toxicity limits their regular use. In
      order to utilize the fatty acid as a safe enhancer devoid of its irritant effect,
      we have synthesized and evaluated a series of fatty acids conjugated to propylene
      glycol (FA-PG). Each one of the conjugates was prepared as a mono- or di- acyl
      ester derivative. The effects of the synthetic enhancers on the porcine skin
      permeability were evaluated in a diffusion cell system using lidocaine as the
      model drug. In addition, in vivo examinations in rabbits were preformed for skin
      toxicological evaluation. The results indicate that among the FA-PG conjugates,
      oleic acid (C18:1(n-9))-PG, linoleic acid (C18:2(n-6))-PG and alpha-linolenic
      acid (C18:3(n-3))-PG, mono- or di-esters, enhance the penetration of lidocaine
      relatively to the vehicle (without enhancer). The conjugates of oleic acid
      (C18:1(n-9)) and linoleic acid (C18:2(n-6)) with PG have demonstrated a similar
      enhancing effect as the corresponding free fatty acids. Interestingly, although
      the mono- or the di- conjugates of alpha-linolenic acid (C18:3(n-3)) with PG
      enhanced the lidocaine flux as the other two fatty acid conjugates, they resulted
      in a reduced permeability as compared to the action of their free acid. In
      addition, the mono-conjugates of alpha-linolenic acid (C18:3(n-3)) with PG
      exhibited elevated skin irritation in rabbits (relative to the fatty acid alone)
      compared to the significantly reduced irritation of oleate-PG and linoeate-PG
      mono-conjugates. In conclusion, except saturated FA-PG and alpha-linolenic acid
      (C18:3(n-3)) - PG mono-conjugates, unsaturated fatty acids (e.g., oleic and
      linoleic acids) after conjugation to PG may be safe and effective enhancers for
      delivering topical drugs.

PMID- 18058313
TI  - Formulation compatibility of myristyl nicotinate with drugs used to treat
      dermatological conditions involving an impaired skin barrier.
AB  - A number of dermatology conditions including skin photodamage, atopic dermatitis,
      and rosacea involve skin barrier impairment and first line therapies for these
      conditions including retinoids and steroids further impair skin barrier function.
      We have evaluated the compatibility of myristyl nicotinate, an agent that
      enhances skin barrier function, with drugs used to treat conditions where skin
      barrier impairment is present including photodamage (retinoic acid), atopic
      dermatitis (hydrocortisone, triamcinolone acetonide), rosacea (metronidazole),
      and seborrheic dermatitis (ketoconazole). Myristyl nicotinate was found to be
      compatible with each of the drugs examined when formulated together and also was
      shown to be photocompatible with retinoic acid. Our results suggest that the
      combination of myristyl nicotinate with these drugs is a feasible therapeutic
      development strategy.

PMID- 18058314
TI  - Formulation design of an HPMC-based sustained release tablet for pyridostigmine
      bromide as a highly hygroscopic model drug and its in vivo/in vitro dissolution
      properties.
AB  - Pyridostigmine bromide (PB), a highly hygroscopic drug was selected as the model
      drug. A sustained-release (SR) tablet prepared by direct compression of wet
      extruded and spheronized core pellets with HPMC excipients and exhibited a zero
      order sustained release (SR) profile. The 2(3) full factorial design was utilized
      to search an optimal SR tablet formulation. This optimal formulation was followed
      zero-order mechanism and had specific release rate at different time intervals
      (released % of 1, 6, and 12 hr were 15.84, 58.56, and 93.10%). The results of
      moisture absorption by Karl Fischer meter showed the optimum SR tablet could
      improve the hygroscopic defect of the pure drug (PB). In the in vivo study, the
      results of the bioavailability data showed the T(max) was prolonged (from 0.65 +/
      0.082 hr to 4.83 +/- 1.60 hr) and AUC(0-t) (from 734.88 +/- 230.68 ng/ml.hr to
      1153.34 +/- 488.08 ng/ml.hr) and was increased respectively for optimum PB-SR
      tablets when compared with commercial immediate release (IR) tablets.
      Furthermore, the percentages of in vitro dissolution and in vivo absorption in
      the rabbits have good correlation. We believe that PB-SR tablets designed in our
      study would improve defects of PB, decrease the frequency of administration and
      enhance the retention period of drug efficacy in vivo for personnel exposed to
      contamination situations in war or terrorist attacks in the future.

PMID- 18058315
TI  - A long acting ophthalmic gel formulations of atenolol.
AB  - The main aim of pharmacotherapeutics, is the attainment of an effective drug
      concentration at the intended site of action for a sufficient period of time to
      elicit the response. In this study a trial was made to formulate atenolol, which
      is a beta-adrenergic blocker in a topical ophthalmic gel. Two polymers were used
      in this study, carboxymethylcellulose and sodium alginate in different
      concentrations. Atenolol was used in concentrations 0.5, 1, and 1.5% w/v. The in
      vitro release study was carried out. The results showed that the release rate of
      atenolol from gel preparations decreased as an inverse function of polymer
      concentration, while the release rate of the drug increased as the initial
      concentration increased. The data of drug release from the two polymers in
      different concentrations was plotted against the square root of time, and the
      diffusion coefficients (D), were calculated from the slope of the equation. Intra
      ocular pressure (IOP) measurements of the rabbit's eye treated with 1% w/v
      atenolol solution, and 1% w/v atenolol in two gel formulations with different
      concentrations of the polymer were determined. The two gel formulations showed
      that these polymers extended the duration of pressure reducing effect to 8 hr,
      when compared with atenolol solution. Area above the curve (AAC), maximum
      response, maximum time of response (t(max)), and the duration of action were
      calculated. The overall results of this study indicated that the gel formulations
      of atenolol could be used for the development of a long-acting ophthalmic
      formulation.

PMID- 18058316
TI  - Chiral separation of alkylamine antihistamines in pharmaceuticals by capillary
      isotachophoresis with charged cyclodextrin.
AB  - Cyclodextrin-mediated capillary isotachophoresis (ITP) in cationic regime of the
      separation was developed for the separation and quantitation of alkylamine
      antihistamine dimethindene (DIM) and pheniramine (PHM) enantiomers in various
      pharmaceutical preparations (capsules, oral drops, gel, granulated powder).
      Several electrolyte systems of different compositions and pH were examined. The
      optimized chiral ITP electrolyte system was consisted of 10 mmol/L potassium
      acetate adjusted to pH 4.8 with acetic acid, containing 4 mmol/L negatively
      charged CE-beta-CD (chiral selector) as the leading electrolyte with
      electroosmotic flow (EOF) suppressing additive, 0.2% (w/v)
      methylhydroxyethylcellulose (m-HEC), and 5 mmol/L beta-alanine as the terminating
      electrolyte. The proposed electrophoretic method was successfully validated. It
      was convenient for the sensitive, simple, rapid, and highly reproducible assay of
      these antihistamine enantiomers. The calibration graphs relating the ITP zone
      length to the concentration of DIM and PHM enantiomers were rectilinear (r =
      0.999) in the range 40.0-200.0 mg/L of each enantiomer. The relative standard
      deviations (RSD) were 0.75% for DIM(1), 0.63% for DIM(2), 1.05% for PHM(1), and
      0.83% for PHM(2) (n = 6) when determining 100 mg/L DIM and PHM, respectively,
      standard solutions. According to the validation procedure based on the standard
      addition technique the recoveries were 97.66-98.34%. Good quantitation was
      obtained in short analysis time (a single analysis took about 12 min). The
      minimal sample pretreatment and low running costs make the proposed ITP method a
      good alternative to commonly used analytical methods (CZE, HPLC). The obtained
      results suggest that the proposed method is suitable for routine assay of
      dimethindene and pheniramine enantiomers in various pharmaceuticals.

PMID- 18058317
TI  - Fexofenadine/cyclodextrin inclusion complexation: phase solubility,
      thermodynamic, physicochemical, and computational analysis.
AB  - Interactions of fexofenadine (Fexo) with cyclodextrins (CDs: alpha- beta-, gamma
      , and HP-beta-CD) were investigated by several techniques including phase
      solubility, differential scanning calorimetry (DSC), X-ray powder diffractometry
      (XRPD), (1)H-nuclear magnetic resonance ((1)H-NMR) and molecular mechanical
      modeling (MM(+)). The effects of CD type, pH, ionic strength, and temperature on
      complex stability were also explored. Fexo/CD complex formation follows the
      decreasing order: beta-CD > HP-beta-CD > gamma-CD > alpha-CD (i.e., at pH 7.0 and
      30 degrees C, K(11) = 1139, 406, 130, and 104 M(-1), respectively). The linear
      correlation of the free energy of Fexo/beta-CD complex formation (DeltaG(11))
      with the free energy of inherent Fexo solubility (DeltaG(So)), obtained from the
      variation of K(11) with inherent Fexo solubility (S(o)) at different pHs and
      ionic strengths, was used to measure the contribution of the hydrophobic
      character of Fexo to escape from water by including into the hydrophobic CD
      cavity. The hydrophobic effect (desolvation) contributes about 76% of the total
      driving force towards inclusion complex formation, while specific interactions
      contribute -7.7 kJ/mol. Moreover, Zwitterionic Fexo/beta-CD complex formation
      appears to be driven both by favorable enthalpy (DeltaH degrees = -23.2 kJ/mol)
      and entropy (DeltaS degrees = 15.2 J/molxK) changes at pH 7.0. (1)H-NMR and MM(+)
      studies indicate multimodal inclusion of the piperidine, carboxypropylphenyl, and
      phenyl moieties into the beta-CD cavity. MM(+) computations indicate that the
      dominant driving force for complexation is Van der Waals force with very little
      electrostatic contribution. (1)H-NMR, DSC, and XRPD studies indicate the
      formation of inclusion complex in aqueous solution and the solid state.

PMID- 18058318
TI  - Improved compaction and packing properties of naproxen agglomerated crystals
      obtained by spherical crystallization technique.
AB  - Naproxen was crystallized from acetone-water in the presence of different
      concentrations of hydroxypropylcellulose (HPC). Naproxen particles recrystallized
      in the presence of HPC exhibited an obvious improvement in their packing, flow,
      and mechanical properties compared to naproxen recrystallized in the absence of
      the polymer (control particles). The results showed that the particle size
      distributions of the treated samples were broader than those obtained when HPC
      was absent. The agglomerates produced in the presence of 0.25% HPC displayed
      superior flow characteristics (displaying both a low angle of repose and Carr
      index) in comparison to samples produced in the presence of other concentrations
      of HPC. This was attributed to the spherical shape and smooth surface, since the
      area of contact in the powder bed for spherical agglomerates was smaller than
      that for other crystal shapes. However it was found that the tensile strength of
      tablets with the particles isolated in the presence of 1% HPC was increased to a
      greater extent than tablets produced using the spherical particles. Generally,
      the tensile strengths of the tablets increased with increasing concentrations of
      HPC present in the crystallization medium. Differential scanning calorimetry
      (DSC) and X-ray powder diffraction studies showed that naproxen particles,
      crystallized in the presence of HPC did not undergo structural modifications.

PMID- 18058319
TI  - Formulation and evaluation of rapidly disintegrating fenoverine tablets: effect
      of superdisintegrants.
AB  - The objective of this study was to formulate directly compressible rapidly
      disintegrating tablets of fenoverine with sufficient mechanical integrity,
      content uniformity, and acceptable palatability to assist patients of any age
      group for easy administration. Effect of varying concentrations of different
      superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch
      glycolate on disintegration time was studied. Tablets were evaluated for weight
      variation, thickness, hardness, friability, taste, drug content, in vitro and in
      vivo disintegration time, and in vitro drug release. Other parameters such as
      wetting time, water absorption ratio ('R'), and drug-excipient compatibility were
      also evaluated. The disintegration time of the best rapidly disintegrating tablet
      formulation among those tested was observed to be 15.9 sec in vitro and 37.16 sec
      in vivo. Good correlation was observed between disintegration time and 'R' for
      each of the three superdisintegrants at the concentrations studied. Considering
      the 'R' values and disintegration time, crospovidone was significantly superior
      (p < 0.05) compared to the other superdisintegrants tested. Release of drug was
      faster from formulations containing 6% crospovidone (CP 6) compared to the
      marketed fenoverine (Spasmopriv(R)) capsules. Similarity factor 'f(2)' (51.5)
      between dissolution profiles of the rapidly disintegrating tablet formulation CP
      6 and the marketed formulation indicated that the two dissolution profiles were
      similar. Differential scanning calorimetric studies did not indicate any
      excipient incompatibility, either during mixing or after compression. In
      conclusion, directly compressible rapidly disintegrating tablets of fenoverine
      with lower friability, acceptable taste, and shorter disintegration times were
      obtained using crospovidone and other excipients at optimum concentrations.

PMID- 18058320
TI  - An effective desiccant system to regulate the humidity inside the chambers of the
      solid dosage forms.
AB  - The most common way to protect moisture-sensitive pharmaceutical powders is to
      utilize protective packaging. However, the most convenient package materials are
      all permeable to water molecules to some extent and limited protection is
      normally achieved with this arrangement even though desiccants are employed. In
      the present study we introduce a novel system that can regulate the internal
      humidity of the containers used with solid dosage forms for a desired time at a
      requested level. Instead of the widely used solid adsorbents the system utilizes
      saturated salt solutions loaded in desiccant bags made of various polymer
      materials with appropriate permeation properties. By utilizing salt solutions the
      size of the desiccant bag can be further reduced. A wide variety of commonly used
      powder chambers and desiccant bags are tested, proving the effectiveness of the
      introduced system.

PMID- 18058321
TI  - Determination of the surface energy distributions of different processed lactose.
AB  - Particulate interactions between drug and lactose carrier in dry powder inhaler
      formulations are affected by the heterogenous energy distribution on the surface
      of the individual compounds. A new method based on Inverse Gas Chromatography at
      finite concentration is applied to study the energy heterogeneity of untreated,
      milled, and recrystallized lactose of similar particle size distribution. Energy
      distributions for the dispersive surface energy and the specific free energy of
      ethanol are obtained. Milling causes an increase in surface energy due to
      formation of amorphous regions. Untreated and recrystallized materials have
      similar surface energies at low surface coverages but show clear differences in
      energy distribution.

PMID- 18058322
TI  - Chitosan nanoparticles for prolonged delivery of timolol maleate.
AB  - Timolol maleate-loaded chitosan (CS) nanoparticles were prepared by desolvation
      method. Experimental variables such as molecular weight of CS and amount of
      crosslinking agent were varied to study their effect on drug entrapment
      efficiency, size and release rates of nanoparticles. Chemical stability of
      timolol maleate (TM) and crosslinking of CS were confirmed by Fourier transform
      infrared spectroscopy. Differential scanning calorimetric studies were performed
      on drug-loaded nanoparticles to investigate crystalline nature of the drug after
      entrapment. Results indicated amorphous dispersion of drug in the polymer matrix.
      Scanning electron microscopy revealed irregularly shaped particles. Mean particle
      size of nanoparticles ranged between 118 and 203 nm, while zeta potential ranged
      between +17 and +22 mV. Entrapment efficiency of nanoparticles ranged between
      47.6 and 63.0%. In-vitro release studies were performed in phosphate buffer
      saline of pH 7.4. A slow release of TM up to 24 h was observed. A 3(2) full
      factorial design was employed and second-order regression models were used to
      study the response (% drug release at 4 h). Release data as analyzed by an
      empirical relationship suggested that drug release deviated from the Fickian
      trend.

PMID- 18058323
TI  - Solubility of core materials in aqueous polymeric solution effect on
      microencapsulation of curcumin.
AB  - Curcumin, the main active constituent of turmeric herb (Curcuma longa L.) have
      been reported to possess many medicinal values. The application of curcumin in
      dermatological preparations is limited by their intense yellow color property,
      which stains the fabric and skin. The objectives of this study were to reduce the
      color staining effect and enhance the stability of curcumin via
      microencapsulation using gelatin simple coacervation method. As for curcumin,
      ethanol and acetone were used as coacervating solvents. Curcumin was dispersed in
      ethanol while dissolved in acetone. Irrespective of the types of coacervating
      solvents used, microencapsulation resolved the color-staining problem and
      enhanced the flow properties and photo-stability of curcumin. Nevertheless, it
      was found that more spherical curcumin microcapsules with higher yield, higher
      curcumin loading, and higher entrapment efficiency were obtained with acetone
      than ethanol. The in vitro release of curcumin after microencapsulation was
      slightly prolonged. Further evaluation of the effects of solubility of core
      materials in coacervating solvent or polymeric aqueous solution using six
      different drug compounds, namely, ketoconazole, ketoprofen, magnesium stearate,
      pseudoephedrine HCl, diclofenac sodium, and paracetamol, suggested that the
      solubility of core materials in aqueous polymeric solution determined the
      successful formation of microcapsules. Microcapsules could only be formed if the
      core materials were not dissolved in the aqueous polymeric solution while the
      core materials could either be dissolved or dispersed in the coacervating
      solvent. In summary, microencapsulation not only circumvents the color-staining
      problem but also improved the stability and flowability of curcumin. The
      solubility of core material in aqueous polymeric solution plays a pivotal role in
      determining the successful formation of microcapsules.

PMID- 18058324
TI  - A cross-performance relationship between Carr's index and dissolution rate
      constant: the study of acetaminophen batches.
AB  - The aim of this paper is to promote a simple and scalable approach to accelerate
      the formulation development of wet granules using acetaminophen batches as a
      model system. Only two thorough experiments with five processing steps of:
      crystallization --> dry blending --> wet granulation --> drying --> dissolution,
      were required to establish a specific linear relationship between the overall
      effect of the particle size distribution and the dissolution performance for a
      given formulation of any batch of acetaminophen. With this specific linear
      relationship at hand, dissolution rates of the granules prepared from batches of
      acetaminophen with various particle size distribution could be predicted without
      the need of doing any wet granulation, drying and dissolution for the same
      formulation. It was found that the Carr's Index, C, an overall manifestation of
      particle size distribution, of only a few grams of the dry blended acetaminophen
      was good enough to be linearly related to the dissolution rate constant, k, of
      the formulated granules by ln k = alpha ln C + ln A (or exponentially by a power
      law of k = AC(alpha)) where A was the exponential factor and alpha was the power
      index. A and alpha were dependent on the mass transfer of acetaminophen powders
      and the rheological properties of the formulated dry blended powders,
      respectively. The three linear relationships for 75, 62, and 30 wt % formulations
      were ln k = 2.9 ln C -12.3, ln k = 2.8 ln C -12.5, and ln k = 4.2 ln C -18.0,
      respectively. The power laws for 75, 62, and 30 wt % formulations were k = 4.7 x
      10(-6) C(2.9), k = 3.9 x 10(-6) C(2.8), and k = 1.5 x 10(-8) C(4.2),
      respectively. The formulation used in our study contained acetaminophen,
      microcrystalline cellulose, and polyvinylpyrrolidone. The validation of the
      linearity between k and C was verified (1) by acetaminophen batches from
      different processes and sources, (2) by the various formulation compositions of
      acetaminophen of 75, 62, and 30 wt%, and (3) by the growth mechanisms of wet
      granulation and the resultant granular structures determined by dry sieve
      analysis, optical microscopy (OM), mercury intrusion porosimetry (MIP), the
      Brunauer-Emmett-Teller (BET) method, scanning electron microscopy (SEM), and
      Fourier transformed infrared (FT-IR) microscopic mapping. In general, granules
      grown from the small-size ranged acetaminophen powders of a given formulation had
      a higher C. Since the growth mechanism was dominated by agglomeration, the
      granules were more porous, higher in surface area, more homogenous, and higher in
      dissolution rate constant, k, as opposed to granules grown from the large-size
      ranged acetaminophen powders of a given formulation having a lower, C, whose
      growth was dominated via consolidation and layer-by-layer mechanism and resulted
      in a lower dissolution rate constant, k.

PMID- 18058328
TI  - Interaction between valproic acid and carbapenem antibiotics.
AB  - The serum concentration of valproic acid (VPA) in epilepsy patients decreased by
      the administration of carbapenem antibiotics, such as meropenem, panipenem or
      imipenem, to a sub-therapeutic level. This review summarized several case reports
      of this interaction between VPA (1-4 g dose) and carbapenem antibiotics to
      elucidate the possible mechanisms decreasing VPA concentration by carbapenem
      antibiotics. Studies to explain the decrease were carried out using rats by the
      following sites: absorption of VPA in the intestine, glucuronidation in the
      liver, disposition in blood and renal excretion. In the intestinal absorption
      site, there are two possible mechanisms: inhibition of the intestinal transporter
      for VPA absorption by carbapenem antibiotics, and the decrease of beta
      glucuronidase supplied from enteric bacteria, which were killed by antibiotics.
      This is consistent with a view that the decrease of VPA originated from VPA-Glu,
      relating to entero-hepatic circulation. The second key site is in the liver,
      because of no decreased in VPA level by carbapenem antibiotics in hepatectomized
      rats. There are three possible mechanisms in the liver to explain the decreased
      phenomenon: first, decrease of the UDPGA level by carbapenem antibiotics. UDPGA
      is a co-factor for UDP-glucuronosyltransferase (UGT)-mediated glucuronidation of
      VPA. Second, the direct activation of UGT by carbapenem antibiotics. This
      activation was observed after pre-incubation of human liver microsomes with
      carbapenem antibiotics. Third, the inhibition of beta-glucuronidase in liver by
      carbapenem antibiotics and the decreased VPA amount liberated from VPA-Glu. The
      third site is the distribution of VPA in blood (erythrocytes and plasma). Plasma
      VPA distributed to erythrocytes by the inhibition of transporters (Mrp4), which
      efflux VPA from erythrocytes to plasma, by carbapenem antibiotics. The increase
      of renal excretion of VPA as VPA-Glu depends on the increase of VPA-Glu level by
      UGT. One or a combination of some factors in these mechanisms might relate to the
      carbapenem-mediated decrease of the plasma VPA level.

PMID- 18058329
TI  - Drug-metabolizing enzymes in the skin of man, rat, and pig.
AB  - The mammalian skin has long been considered to be poor in drug metabolism.
      However, many reports clearly show that most drug metabolizing enzymes also occur
      in the mammalian skin albeit at relatively low specific activities. This review
      summarizes the current state of knowledge on drug metabolizing enzymes in the
      skin of human, rat, and pig, the latter, because it is often taken as a model for
      human skin on grounds of anatomical similarities. However only little is known
      about drug metabolizing enzymes in pig skin. Interestingly, some cytochromes P450
      (CYP) have been observed in the rat skin which are not expressed in the rat
      liver, such as CYP 2B12 and CYP2D4. As far as investigated most drug metabolizing
      enzymes occur in the suprabasal (i.e. differentiating) layers of the epidermis,
      but the rat CYP1A1 rather in the basal layer and human UDP
      glucuronosyltransferase rather in the stratum corneum. The pattern of drug
      metabolizing enzymes and their localization will impact not only the beneficial
      as well as detrimental properties of drugs for the skin but also dictate whether
      a drug reaches the blood flow unchanged or as activated or inactivated
      metabolite(s).

PMID- 18058330
TI  - Drugs as CYP3A probes, inducers, and inhibitors.
AB  - Human cytochrome P450 (CYP) 3A subfamily members (mainly CYP3A4 and CYP3A5)
      mediate the metabolism of approximately half all marketed drugs and thus play a
      critical role in the drug metabolism. A huge number of studies on CYP3A-mediated
      drug metabolism in humans have demonstrated that CYP3A activity exhibits marked
      ethnic and individual variability, in part because of altered levels of CYP3A4
      expression by various environmental factors and functionally important
      polymorphisms present in CYP3A5 gene. Accumulating evidence has revealed that
      CYP3A4 and CYP3A5 have a significant overlapping in their substrate specificity,
      inducers and inhibitors. Therefore, it is difficult to define their respective
      contribution to drug metabolism and drug-drug interactions. Furthermore, P
      glycoprotein and CYP3A are frequently co-expressed in the same cells and share a
      large number of substrates and modulators. The disposition of such drugs is thus
      affected by both metabolism and transport. In this review, we systematically
      summarized the frequently used CYP3A probe drugs, inducers and inhibitors, and
      evaluated their current status in drug development and research.

PMID- 18058331
TI  - The emerging importance of transporter proteins in the psychopharmacological
      treatment of the pregnant patient.
AB  - P-glycoprotein, breast cancer resistance protein, and multidrug resistance
      proteins have physiological functions in placental tissue. Several
      antidepressants, antipsychotics, and anti-epileptic drugs have been found to be
      substrates of P-glycoprotein and other transporters. The extent that drugs pass
      through the placental barrier is likely influenced by drug transporters. The
      rational choice of psychoactive drugs to treat mental illness in women of child
      bearing age should incorporate knowledge of both drug disposition as well as
      expected pharmacologic effects. This review summarizes the current data on drug
      transporters in the placental passage of medications, with a focus on medications
      used in clinical psychopharmacology.

PMID- 18058332
TI  - Effect of 7, 14 and 21 Hz modulated 450 MHz microwave radiation on human
      electroencephalographic rhythms.
AB  - PURPOSE: The aim of this study was to evaluate the effect of microwaves modulated
      at different frequencies on human electroencephalographic (EEG) rhythms.
      MATERIALS AND METHODS: Thirteen healthy volunteers were exposed to microwaves
      (450 MHz) pulse-modulated at frequencies of 7, 14 and 21 Hz. The field power
      density at the scalp was 0.16 mW/cm2. Our experimental protocol consisted of two
      five-cycle (1 min on and 1 min off) series of exposures at fixed modulation
      frequencies. A relative change in the EEG power with and without exposure was
      used as a quantitative measure. EEG frequencies recorded in the theta (4-6.8 Hz),
      alpha (8-13 Hz), betal (15-20 Hz), and beta2 (22-38 Hz) bands were analyzed.
      RESULTS: Modulated microwaves caused an increase in the average EEG alpha (17%)
      and beta (7%) power but the theta rhythm remained unaffected. Increases in the
      EEG alpha and beta power were statistically significant during the first half
      period of the exposure interval (30 s) at the modulation frequencies of 14 and 21
      Hz. Differences were found in individual sensitivity to exposure. Increases in
      the EEG beta power appeared statistically significant in the case of four
      subjects. CONCLUSIONS: Our findings suggest that the effect of the 450 MHz
      microwave radiation modulated at 7, 14 and 21 Hz varies depending on the
      modulation frequency. The microwave exposure modulated at 14 and 21 Hz enhanced
      the EEG power in the alpha and beta frequency bands, whereas no enhancement
      occurred during exposure to the modulation frequency of 7 Hz.

PMID- 18058334
TI  - Speaking your mind: measuring the subjective quality of life of children with
      mental illnesses.

PMID- 18058335
TI  - Health diaries for self-monitoring and self-regulation: applications to
      individuals with serious mental illness.
AB  - Various health promotion interventions have been developed for individuals with
      serious mental illness that address such problems as medication nonadherence and
      physical inactivity. The beneficial outcomes of these interventions may be
      enhanced or extended if patients used a tool to monitor their own health habits.
      A systematic review of studies on health diaries was conducted to inform the
      development of the Monthly Medication Journal. A self-regulation model is
      discussed in using health diaries as self-monitoring and self-regulation tools
      for individuals with various mental health disorders.

PMID- 18058336
TI  - Dual diagnosis: an exploratory qualitative study of staff perceptions of
      substance misuse among the mentally ill in Northern India.
AB  - Dual diagnosis is well recognized as a significant clinical problem. It is
      associated with poor outcomes, staff difficulties, and management problems. This
      exploratory study investigated the extent and clinical correlates of dual
      diagnosis and traditional substance use among the mentally ill by interviewing
      staff from several substance misuse and mental health services in Northern India,
      using a semi-structured interview schedule and focus groups. Dual diagnosis was
      seen as a common problem according to staff interviewed from substance misuse and
      mental health services, although types of substance use reported were different
      than in western studies. Traditional substance use (the use of substances in
      distinct cultural, religious, and social settings that is not prohibited, such as
      khat or betel nut) also was reported as common among those with dual diagnosis.
      Substance misuse among the mentally ill is common in Northern India.
      Opportunities exist for informing mental health nursing practice about
      "traditional" substance use.

PMID- 18058337
TI  - The experience of Black consumers in the mental health system--identifying
      barriers to and facilitators of mental health treatment using the consumers'
      perspective.
AB  - Research has shown that relative to Whites, Blacks are less likely to seek
      outpatient mental health treatment and more likely to seek emergency services.
      Furthermore, Blacks often terminate treatment prematurely. The goal of the
      present study was to identify barriers to and facilitators of mental heath
      treatment among Blacks who have a documented need for mental health services.
      Thirty-four Black mental health consumers were interviewed for this purpose.
      Comments were categorized into four main categories: (a) barriers to treatment,
      (b) treatment facilitators, (c) recommendations for improvement of services, and
      (d) advice to potential consumers. The most common barriers were the importance
      of family privacy, lack of knowledge regarding available treatments, denial of
      mental health problems, and concerns about stigma, medications, and treatment.
      Participants also reported system barriers, such as not receiving appropriate
      information about services or receiving inadequate, dehumanizing services.
      Acknowledging the need for mental health services, having a supportive
      environment, and positive past treatment experiences were identified as treatment
      facilitators. Community outreach, adequate follow-up, and coordination of
      services also were important messages delivered by consumers. The results of this
      study indicate the importance of educating the general public, not just mental
      health consumers, about the nature of mental illness and available services.

PMID- 18058338
TI  - Can cultural competence be achieved without attending to racism?

PMID- 18058342
TI  - What's new in nicotine & tobacco research?

PMID- 18058344
TI  - Predictors of smoking onset over two years.
AB  - The objective of this analysis was to identify variables that predict the
      initiation of smoking among adolescents, and the development of susceptibility to
      smoking, over a 2-year period. We assessed variables that might predict later
      smoking among nonsmoking students in grades 7 and 9 and assessed their smoking
      status 2 years later, when they were in grades 9 and 11, thus receiving data from
      4,130 students at two time points. Initiation of weekly smoking over the 2 years
      was associated with having a parent, sibling, or close friend who smokes; low
      school grades; higher levels of deviant behavior; susceptibility to smoking; use
      of smokeless tobacco; and for 7th graders, perception of higher levels of
      normative smoking. Susceptibility, defined as not being able to rule out the idea
      of smoking a year after the survey, was identified as a strong predictor of
      smoking and a valuable intermediary measure. We also assessed factors associated
      with the prediction of susceptibility 2 years post-test. Susceptibility to
      smoking was associated with deviant behavior, low grades, lower parental
      monitoring, relaxed parental attitude toward youth smoking, ease of access to
      tobacco, and lower exposure to anti-tobacco messages. This study provides support
      for the idea that susceptibility to smoking could be a useful outcome variable
      for tobacco research, as an intermediary to the initiation of smoking. In
      addition, evidence indicates that theoretically manipulable variables, including
      access to tobacco and exposure to anti-tobacco information, have the potential to
      influence susceptibility to smoking over a time.

PMID- 18058343
TI  - Bupropion efficacy for smoking cessation is influenced by the DRD2 Taq1A
      polymorphism: analysis of pooled data from two clinical trials.
AB  - We analyzed pooled data from two comparable randomized placebo-controlled
      clinical trials of bupropion pharmacotherapy for smoking cessation for which data
      on DRD2 Taq1A genotype were available. A total of 722 smokers across the two
      trials were randomized to 10 weeks of sustained-release bupropion hydrochloride
      or placebo. General estimating equation analysis demonstrated a significant gene
      x drug interaction (B = 0.87, SE = 0.34, p = .009). Smokers with the A2/A2
      genotype using bupropion were more than three times as likely, relative to
      placebo, to be abstinent at end of treatment (35.2% vs. 15.1%; OR = 3.25, 95% CI
      2.00-5.28) and at 6 months of follow-up (26.7% vs. 12.2%; OR = 2.81, 95% CI 1.66
      4.77), which was attenuated by 12 months (16.3% vs. 10.7%; OR = 1.70, 95% CI 0.95
      3.05). We found no significant benefit of bupropion relative to placebo on
      smoking cessation outcomes at any time point in participants with A1/A1 or A1/A2
      genotypes. These data suggest that bupropion may be effective for smoking
      cessation only in a subgroup of smokers with the DRD2 Taq1 A2/A2 genotype.

PMID- 18058345
TI  - The demand for health insurance coverage for tobacco dependence treatments:
      support for a benefit mandate and willingness to pay.
AB  - One solution for reducing tobacco use is to expand health insurance coverage for
      tobacco dependence treatments (TDTs), but the public demand for a coverage
      mandate is unknown. This study finds that demand for coverage of TDTs among a
      random sample of adult Californians with employer-sponsored health insurance is
      strong, with 62% indicating that health insurers should be required to offer
      coverage as part of their standard plans and a majority (56%) indicating a
      willingness to pay $3 more for their annual health insurance premium to finance
      cessation coverage. Compared to never smokers, current and former smokers are no
      more likely to support a benefit mandate to require coverage of cessation
      treatments, but the adjusted odds are approximately three times greater that
      current and former smokers are willing to pay $3 more toward their annual premium
      to finance cessation coverage. Liberals had higher adjusted odds of supporting a
      benefit mandate and of being willing to pay a higher premium compared to
      conservatives. Non-whites had higher adjusted odds of supporting a mandate
      compared to whites, with no differences by race/ethnicity in willingness to pay a
      higher premium. There were no differences in preferences for a benefit mandate or
      willingness to pay a higher premium as a function of age, gender or income. These
      findings have important policy implications for a state health insurance mandate
      to cover tobacco dependence treatments.

PMID- 18058346
TI  - The first puff: forces in smoking initiation among Californians of Korean
      descent.
AB  - This study presents the correlates of initial exposure to cigarettes, variables
      associated with smoking prevalence and with continued smoking (or not) among
      adult Californians of Korean descent who have any initial exposure to cigarettes.
      Among those who have taken a puff, social contingencies contrast those who become
      current smokers from those who do not. Data were drawn from telephone interviews
      with adults (N = 2,830) developed from a random sampling of listed persons in
      California with Korean surnames during 2000-2001. Of the attempted interviews,
      86% were completed; and 85% of the interviews were conducted in Korean. Nearly
      half of all respondents (49.0%) had been exposed to cigarettes, and 41.9% of
      these reported current smoking, according to Centers for Disease Control and
      Prevention criteria (currently smoke and have smoked 100 cigarettes during
      lifetime). Multivariate analysis suggests that social contingencies may influence
      both initial exposure to tobacco and continued smoking among Californians of
      Korean descent. Influences of acculturation on taking the first puff and on
      current smoking status diverged by gender. Social support increased the
      likelihood of the first puff among both genders, but the association was stronger
      among females than among males. Social reinforcers that lead to taking the first
      puff also discriminated between those who became current smokers and those who
      did not. Interventions should be directed at these variables among young Korean
      nonsmokers and new smokers.

PMID- 18058347
TI  - Examining trends in quantity smoked.
AB  - Although the quantity smoked is known to affect smokers' health risks and
      likelihood of cessation, little is known about trends in quantity smoked and the
      role of policies in affecting those trends. We examined trends in quantity smoked
      using a new measure derived from U.S. Department of Agriculture per-capita
      cigarette consumption (PCC) and smoking prevalence data. We compared this measure
      to a survey measure of mean cigarettes smoked per day from the National Health
      Interview Survey (NHIS). Using our measure, we examined trends in quantity smoked
      at the national level from 1974 to 2004 and for two states, California and
      Massachusetts. We used regression analysis to distinguish price and other policy
      related trends from long-term trends. The derived measure of quantity tracked
      well with the NHIS measure. Through 1990, changes in quantity were well explained
      by price changes, with no residual trend in quantity smoked. Since 1990, price
      showed similar effects, but a downward trend was observed. In California and
      Massachusetts the initiation of a comprehensive tobacco program as well as price
      and tax changes were found to explain trends in quantity smoked. Continued
      progress in reducing the quantity smoked is likely to require the consistent
      implementation of current policies and the introduction of new policies. Although
      sustained reductions in quantity smoked may take a long time to affect smokers'
      health outcomes, sustained reductions appear to be related to cessation. The
      measure developed in the present study provides a useful tool for tracking trends
      in quantity smoked.

PMID- 18058348
TI  - Association of post-treatment smoking change with future smoking and cessation
      efforts among adolescents with psychiatric comorbidity.
AB  - Little is known about how initial change following a smoking intervention relates
      to longer-term smoking outcomes among adolescent smokers with psychiatric
      comorbidity. The present study investigated this relationship among
      psychiatrically hospitalized adolescents (N = 183) who participated in a
      controlled trial comparing motivational interviewing to brief advice. Quit
      attempters (n = 37), reducers (n = 45), and maintainers (n = 101) were assembled
      based on, respectively, having made a quit attempt, having reduced smoking by at
      least 50%, and having reduced smoking by less than 50% in the first week after
      hospital discharge. Hierarchical linear models and generalized estimating
      equations were conducted to test group differences in average number of
      cigarettes per smoking day and odds of making a quit attempt during subsequent
      weeks of a 12-month continuous follow-up, and in cotinine-verified abstinence
      rates at 1, 6, and 12 months posthospitalization. Baseline smoking levels and
      presence of a substance use disorder or anxiety disorder were predictive of
      outcomes. After controlling for covariates, we found that quit attempters smoked
      less during follow-up than did the other change groups and that reducers smoked
      less than maintainers. Quit attempters evidenced a higher percentage of quit
      attempts during follow-up than did the other change groups. Reducers had a
      greater average percentage of quit attempts during follow-up than did
      maintainers. However, groups did not differ on cotinine-verified abstinence rates
      across the follow-up period. Findings have implications for initial post
      treatment change as it relates to subsequent smoking and cessation outcomes among
      adolescent smokers at especially high risk for smoking persistence.

PMID- 18058349
TI  - Pilot study on lower nitrosamine smokeless tobacco products compared with
      medicinal nicotine.
AB  - Smokeless tobacco (ST) products have the potential to be used as a harm reduction
      method for cigarette smokers. These products can deliver significantly less
      toxicants than cigarettes, although they are not toxicant free nor harmless. It
      is important to examine potential health risks and benefits of these products.
      These two small pilot studies examined the effects of two different ST products
      (Exalt and Ariva) compared with medicinal nicotine, another potential harm
      reduction product. Dependent, healthy adult cigarette smokers, who were motivated
      to quit smoking, underwent 1 week of baseline smoking measurement. They were then
      asked to quit smoking and were randomly assigned to use either an ST product or a
      medicinal nicotine lozenge (MNL, Commit) for 2 weeks, then crossed over to use
      the other product for 2 weeks. In the last week, following the sampling phase,
      subjects could choose the product they wished to use. Assessments were made
      repeatedly during baseline cigarette use and throughout the 5 weeks of treatment.
      Outcome measures included biomarkers for tobacco exposure and subjective,
      physiological, and behavioral responses. Tobacco-specific carcinogen uptake was
      greater from Exalt than from the MNL, and was comparable between the MNL and
      Ariva. Physiological effects and subjective effects on withdrawal and craving
      were comparable among Exalt, Ariva, and the MNL. Ariva was preferred over the
      MNL, which was preferred over Exalt. With the exception of medicinal nicotine
      products, low-nitrosamine ST products have the greatest potential to result in
      reduced toxicant exposure compared with other combustible reduced exposure
      products and have promise for reducing individual risk for disease. However, the
      population effect of marketing of such products as reduced exposure/reduced risk
      is unknown. The need for further research in this area and regulation of tobacco
      products is evident.

PMID- 18058350
TI  - DRD2/ANKK1 TaqI polymorphism and smoking behavior of Egyptian male cigarette
      smokers.
AB  - Little is known about the genetic contribution to cigarette smoking and nicotine
      addiction in Egypt. The dopamine D2 receptor gene contains a TaqI repeat fragment
      length polymorphism creating two alleles with functional significance, DRD2*A1
      and DRD2*A2. We investigated the relationship between these alleles and tobacco
      use in a study of 389 Egyptian male current smokers (mean age = 40 years; SD =
      12). Participants were interviewed in 2004 on their smoking behaviors and quit
      attempts, and were given the Fagerstrom Test for Nicotine Dependence (FTND).
      Blood samples were obtained and genotyped for DRD2 A1and A2 alleles. The
      frequencies of A1/A2, A1/A2, and A2/A2 genotypes were 6%, 29%, and 65%,
      respectively. We found no statistically significant association between genotype
      and age at onset of smoking, years of smoking, FTND score, or average number of
      cigarettes smoked per day. DRD2 genotype was associated with the number of
      cigarettes smoked in the past 48 hr (42.2 in A1 carriers vs. 37.6 in A2, p =
      .03), the previous quit duration (28% in A1 vs. 40% in A2 quit for more than 1
      month, p = .05), and the depth of inhalation (82% in A1 vs. 72% in A2 inhaled the
      smoke deeply, p = .03). Logistic regression analysis including DRD2 genotype,
      FTND score, age at smoking initiation, marital status, and education as
      predictors showed that maximum duration of quit time was associated with FTND
      score (p = .003), DRD2 genotype (p = .01), marital status (p = .03), and age at
      smoking initiation (p = .04). These findings suggest a modest association between
      DRD2 genotype and quitting behavior in male cigarette smokers in Egypt.

PMID- 18058351
TI  - Use of smokeless tobacco is a risk factor for cigarette smoking.
AB  - This study assessed the risk of smoking uptake over 2 years in adolescent boys
      (in grades 7 and 9) who had used smokeless tobacco (ST). We used logistic
      regression to determine whether the odds of adolescent boys taking up regular
      smoking over a period of 2 years were greater among initial nonsmokers who used
      ST, compared with nonusers of ST, after accounting for six well-established
      predictors of smoking. Initiation of weekly smoking 2 years after baseline was
      associated with ST use at baseline, even after including dichotomous measures of
      parent, sibling, or close friend smoking; low academic grades; 30-day alcohol
      use; and a scale measure of deviant behavior. With these other predictors
      included in the model, the odds ratio for the association of ST use with weekly
      smoking after 2 years was strong and significant (OR = 2.55, 95% CI 1.45-4.47,
      p<.001). The use of ST in the 7th and 9th grades is a significant risk factor for
      subsequent smoking even when controlling for other factors.

PMID- 18058352
TI  - Characteristics of U.S. waterpipe users: a preliminary report.
AB  - Waterpipe smoking, a traditional method of tobacco use, has experienced a
      resurgence in the Middle East and Indian subcontinent in recent years. Despite
      growing evidence of its dependence potential and health-damaging effects,
      waterpipe use has spread beyond these regions to many other countries, including
      the United States. Because little is known about waterpipe use in the United
      States, we surveyed convenience samples of users from two U.S. cities, Richmond,
      Virginia (n = 109), and Memphis, Tennessee (n = 34). Respondents in both cities
      were primarily young adults, a majority (75%) were men, and most were college
      students or had a college degree. Initial and current use usually occurred in a
      social context, with a group of friends in a cafe or restaurant or at home. Most
      respondents had smoked waterpipe for 2 or fewer years, and 67% currently smoked
      at least once a month (22% smoked at least once per week and 10% smoked daily).
      Most believed waterpipe use to be less addictive and harmful than cigarette
      smoking, believed they could quit use at any time, but had no plans or desire to
      quit. A majority of respondents used other tobacco products such as cigarettes,
      and 35% of those who did not smoke cigarettes said they would "probably" or
      "definitely" smoke one in the next year. Multivariate correlates of greater
      frequency of use included younger age at first use, ownership of a waterpipe, use
      occurring primarily with groups of friends, and the perception of being "hooked."
      Waterpipe users in these two convenience samples from the United States were
      young and educated, tended to experiment with multiple forms of tobacco, were
      unaware of the potentially harmful and addictive properties of waterpipe use, and
      planned to continue use in the future. Educational efforts are needed to increase
      awareness of the potential hazards of this increasingly popular form of tobacco
      use.

PMID- 18058353
TI  - Saccadic eye movement velocity measured with the infrared reflection and search
      coil eye-tracking systems in patients with thyroid-associated ophthalmopathy.
AB  - BACKGROUND: Assessment of changes in saccade velocity may be useful in the early
      detection of thyroid-associated ophthalmopathy (TAO). Two eye-tracking systems
      were used to measure the velocity of saccadic eye movements in patients with TAO.
      METHOD: Fourteen patients with active TAO and 14 healthy controls were enrolled
      for recordings with two eye-tracking systems: the magnetic scleral search coil
      (MSC; Skalar Medical) and the infrared reflection systems (IR; Orbit XY-1000).
      The MSC is generally considered the "gold standard" method for tracking of rapid
      eye movements. The IR system uses novel computer technology and is based on
      sampling of reflected infrared light from the surface of the eyes. Main sequence
      plots constructed from the recorded saccadic peak velocity and amplitude were
      analyzed for differences between patients and healthy controls. RESULTS: There
      were no significant differences between patients with TAO and healthy controls in
      the constructed main sequence plots of maximum velocity (V(MAX)) and the slope
      constant (C). CONCLUSIONS: Main sequence analysis of saccadic eye movements was
      not useful for detecting TAO in this experimental setting with either of the two
      eye-tracking methods. This is hypothesized to be due to compensation for the
      early orbital changes in TAO by neural adaptation of the saccades in the brain
      stem. The contradictory results between this and previous studies cannot be
      easily explained. We assume that there is a large heterogeneity in the saccadic
      eye movement performance in both the normal population and the TAO-population.
      Also, differences in the study design may cause dissimilar outcomes and hence
      incoherent conclusions. A non-invasive recording system that is able to generate
      a minimum amount of intra- and inter-individual variability and a study design
      where normal variability can be reduced to a minimum may be useful for future
      identification of early eye muscle changes in TAO.

PMID- 18058354
TI  - Comparison of the temporal hemifield and nasal hemifield sensitivity in patients
      with early-onset convergent strabismus.
AB  - OBJECTIVE: To analyze the hypothesis that a reduction in sensitivity of the nasal
      visual hemifield would lead to an increase in the nasotemporal asymmetry of the
      visual field in patients under two years of age with early-onset convergent
      strabismus in comparison with normal patients. METHODS: Both eyes of 66 patients 
      33 esotropes and 33 normals - were studied. Patients' age ranged from 7 to 30
      years. The examination consisted of a static perimetry using the Humphrey field
      analyzer 700 Series' Sita Standard program. RESULTS: An accentuation of the
      nasotemporal asymmetry was seen in the 33 esotropes and was related to an evident
      decrease of sensitivity in the most peripheral of the points studied along the
      horizontal meridian of the visual field. The quantitative sum of values of
      sensitivity of these points showed an average reduction of -15.71% in relation to
      the normal patients. CONCLUSION: There was a clear accentuation of the
      nasotemporal asymmetry of sensitivity in esotropes when compared to normal
      patients. There was no difference in sensitivity between the two eyes in either
      normals or esotropes.

PMID- 18058355
TI  - The angle kappa in strabismic individuals.
AB  - PURPOSE: To determine angle kappa values in strabismic individuals by means of a
      synoptophore. METHODS: One hundred-and-eight strabismic subjects and 102 healthy
      subjects who served as a control group were enrolled in the study. A complete
      ophthalmologic examination, including determination of refractive status, best
      corrected visual acuity measurement, slit-lamp biomicroscopic anterior segment
      evaluation, intraocular pressure measurements with a Goldmann applanation
      tonometer, and dilated fundus examination, was done on all study participants.
      Orthoptic examination included Krimsky prism reflex test, prism cover test, and
      duction tests. Strabismic patients were grouped into two categories according to
      their deviation types: exotropic and esotropic. A synoptophore (Clement Clarke,
      London, England) with a specially designed slide (Maddox test slide series A
      White Binding No: 16; Clement Clarke, London, England) was used to measure angle
      kappa. RESULTS: Of the 108 strabismic patients, 62 were males and 46 were females
      with a mean age of 23.38 +/- 3.68 years (range: 8 to 82 years). There were 54
      males and 48 females with a mean age of 32.74 +/- 1.63 years (range: 7 to 68
      years) in the control group. The exotropic group had significantly higher angle
      kappa values than either the controls or the esotropic group (independent sample
      t-test, p < 0.001). None of the study participants had negative angle kappa
      values. Higher average kappa values were obtained in left eyes than in right eyes
      in all three groups (student t-test, p < 0.01 for all groups). CONCLUSION: This
      study showed that exotropic patients have higher angle kappa values when compared
      to esotropic patients. Ophthalmologists must take the kappa angle into account
      when performing a Hirschberg or Krimsky test in young and uncooperative patients
      in order to improve surgical results.

PMID- 18058356
TI  - Orthoptists' management of amblyopia - a case-based survey.
AB  - PURPOSE: The aim of this study was to investigate the amblyopia treatment trends
      of Australian orthoptists and to identify variations or consistencies amongst
      treatment patterns. METHODS: A questionnaire was distributed to all orthoptists
      who attended an annual national scientific conference. This questionnaire
      consisted of four case vignettes of amblyopic patients. Each was presented with a
      series of multiple-choice questions that orthoptists were required to answer.
      RESULTS: The questionnaire was completed by 46 orthoptists. Large diversity
      between orthoptists in their treatment application was found. This related mostly
      to the intensity of occlusion treatment. CONCLUSION: Treatment variability
      continues to exist between orthoptists. Further investigations evaluating the
      clinical decision making processes of clinicians in prescribing amblyopia
      treatment may help us to better understand the determinants that are considered
      when prescribing treatment. This would be useful in establishing best-practice
      guidelines.

PMID- 18058357
TI  - Duane retraction syndrome on the Arabian Peninsula.
AB  - PURPOSE: To describe the clinical features of patients from the Arabian Peninsula
      with Duane retraction syndrome (DRS). METHODS: Retrospective chart review of
      patients referred to the King Khaled Eye Specialist Hospital in Riyadh, Saudi
      Arabia from 1982 to 2003 with a diagnosis of DRS. Patients having had prior
      strabismus surgery were excluded. RESULTS: Of 404 DRS patients, 347 (86%) were
      unilateral, 57 (14%) were bilateral, and 111 (27%) had amblyopia. There were 221
      (55%) females and 182 (45%) males. The Huber classification was as follows: 315
      (78%) Type I, 16 (4%) Type II, and 77 (19%) Type III. Of the 57 bilateral cases,
      25 (44%) were female and 32 (56%) were male. DISCUSSION: Overall, the clinical
      features of DRS patients referred to a Riyadh eye hospital are similar to those
      reported in series throughout the world. However, our referred bilateral DRS
      patients are more commonly male. The clinical features of bilateral DRS deserve
      further worldwide study.

PMID- 18058358
TI  - Factors influencing severity of and recovery from anisometropic amblyopia.
AB  - PURPOSE: To evaluate the correlation between the degree of anisometropia with
      depth of amblyopia and presence of stereopsis. METHODS: A retrospective chart
      review of 119 patients treated during 1995-2004 was carried out. All patients had
      undergone a full ophthalmological examination. Inclusion criteria were:
      anisometropia >1 diopter (spherical and/or cylindrical), age at first examination
      between 2 and 8 years, no previous optical correction, absence of ocular and
      neurological disorders, absence of ocular motility disorders, and minimum follow
      up of 2 years (mean 7.9 +/- 4.3). Optical correction was prescribed at first
      visit and, at a second visit, the need for patching or penalization was
      evaluated. RESULTS: The results show a correlation between the degree of
      anisometropia and visual acuity at first visit (p < 0.001). There were, however,
      several subjects with good levels of visual acuity despite considerable
      anisometropia, and also subjects where mild or moderate anisometropia was
      sufficient to induce a severe amblyopia. Compared to other types of
      anisometropia, anisomyopic patients appeared to have a higher degree of binocular
      vision recovery when corrected optically. First evaluation with the presence of
      good stereoacuity seems to be a prognostic indicator for amblyopic recovery.
      CONCLUSIONS: This study demonstrates the difficulty of developing a guideline for
      screening and treatment of anisometropia. Even though there seems to be a
      correlation between type and degree of anisometropia in a majority of patients,
      there is also a significant number of cases that do not follow this pattern.
      Another important observation is the presence of binocular vision at the first
      evaluation as a good prognostic indicator for visual recovery with optical
      correction alone, even without penalization therapy.

PMID- 18058359
TI  - Orbital cellulitis after faden operation on the medial rectus.
AB  - BACKGROUND: Orbital cellulitis after strabismus surgery is uncommon, may cause
      blindness and may lead to death. Very few cases have been described in detail due
      to the low incidence of this complication. METHODS: We report the first case of
      orbital cellulitis following Faden operation on the medial rectus muscle. We
      believe that the infection was due to asymptomatic ethmoid sinusitis. Our case is
      compared with other cases previously reported. RESULTS: A two-year-old boy was
      surgically treated for residual esotropia after two botulinum toxin A injections.
      Two days after surgery, signs of orbital cellulitis developed in his right orbit.
      CT-scan disclosed right ethmoid sinusitis that spread to the orbit after surgery.
      After intravenous antibiotic treatment, the infection resolved with full
      restoration of visual acuity and ocular motility. CONCLUSION: Despite adequate
      measures to prevent infection, orbital cellulitis may complicate strabismus
      surgery. Patients must be instructed to recognize early symptoms of this severe
      infection and call the surgeon immediately. Diagnosis may be confirmed by CT
      scanning of the orbits. Prompt treatment with intravenous antibiotics usually
      leads to full recovery.

PMID- 18058360
TI  - Questions on the movement of the human eye (part II).

PMID- 18058361
TI  - Rapid expansion of human adipose-derived stromal cells preserving multipotency.
AB  - BACKGROUND: Adipose-derived stromal (stem) cells (ASC) have been shown to be of
      great therapeutic use in pre-clinical studies in diverse fields, but a standard
      expansion method has not been established. We investigated the effects of an
      endothelial growth medium (EGM-2) on ASC, focusing on proliferation and
      differentiation potentials. METHODS: ASC were cultured in EGM-2 and DMEM.
      Doubling time and total cell number were compared between the two media. The
      proliferative effect of each growth factor supplemented in EGM-2 was also
      examined. Cultured cells in each medium were examined for surface marker
      expression using flow cytometry. Differentiation into the adipogenic,
      chondrogenic and osteogenic lineages was analyzed after culture in each medium.
      RESULTS: ASC cultured with EGM-2 proliferated much more rapidly (10(5) times in 2
      weeks) and reached the stationary phase earlier than those cultured with DMEM.
      Among the supplements contained in EGM-2, only fibroblast growth factor-2 (FGF-2)
      significantly promoted proliferation of ASC, although the proliferative effect of
      FGF-2 was much less than that of EGM-2, suggesting a synergism among other
      supplement factors. Flow cytometry and differentiation assays suggested that ASC
      cultured in EGM-2 preserved immunophenotype and differentiation capacity for at
      least three mesenchymal lineages (adipogenic, chondrogenic and osteogenic),
      similar to those cultured with DMEM. DISCUSSION: The present expansion method
      markedly accelerates proliferation of ASC, preserving their multipotent
      differentiation capacities, and lays the groundwork for establishing a practical
      route to mega-expansion of ASC for clinical applications.

PMID- 18058363
TI  - Radiation therapy and the microenvironment.

PMID- 18058364
TI  - beta1 integrin as a molecular therapeutic target.
AB  - PURPOSE: Radiation therapy (RT) is a commonly used modality to treat human
      cancer. However, dose-limiting toxicity and resistance are major problems to
      improving treatment efficacy. Increasing evidence has pointed to the critical
      role of the tumor microenvironment and cell-extracellular matrix (ECM),
      specifically via beta1 integrins, in modifying response to therapy, including
      radiation. beta1 integrins have been implicated in several key processes in
      malignant progression and metastasis, and more recently in mediating resistance
      to cytotoxic chemotherapy and radiation. Evidence is mounting that beta1
      integrins mediate essential survival signals post-IR, through both canonical and
      non-canonical integrin signaling pathways that make it a highly promising
      therapeutic target for several solid malignancies. CONCLUSIONS: In this mini
      review article, we briefly summarize the most recent emerging findings concerning
      beta1 integrin and radiation survival that indicate the promise of beta1 integrin
      inhibitory agents as radiosensitizers.

PMID- 18058365
TI  - alpha6 integrin cleavage: sensitizing human prostate cancer to ionizing
      radiation.
AB  - PURPOSE: The goal was to determine if prostate tumor cells containing a mutant
      alpha6 integrin would be defective in tumor re-population following clinically
      relevant fractionated ionizing radiation (IR) treatments. MATERIAL AND METHODS:
      Human prostate cancer cells derived from PC3N cells were used which conditionally
      expressed a cleavable, wild type form of alpha6 integrin (PC3N-alpha6-WT) or a
      mutated non-cleavable form of alpha6 integrin (PC3N-alpha6-RR). The resulting
      tumor growth before, during and after fractionated doses of IR (3 Gyx10 days) was
      analyzed using the endpoints of tumor growth inhibition (T/C), tumor growth delay
      (T-C), tumor doubling time (Td) and tumor cell kill (Log(10) cell kill). RESULTS:
      The T/C values were 36.1% and 39.5%, the T-C values were 20.5 days and 28.5 days
      and the Td values were 5.5 and 10.5 days for the irradiated PC3N-alpha6-WT and
      PC3N-alpha6-RR cells, respectively. The Log(10) was 1.1 for the PC3N-alpha6-WT
      cells and 0.8 for the PC3N-alpha6-RR cells. The tumor response to IR was altered
      in tumors expressing the mutant alpha6 integrin as indicated by a significant
      increase in tumor growth inhibition, an increase in tumor growth delay, an
      increase in tumor doubling time and an increase in tumor cell kill. CONCLUSIONS:
      Blocking integrin cleavage in vivo may be efficacious for increasing the IR
      responsiveness of slow growing, pro-metastatic human prostate cancer.

PMID- 18058366
TI  - Radiation-induced EGFR-signaling and control of DNA-damage repair.
AB  - PURPOSE: Over the last decade evidence has accumulated indicating that cell
      membrane-bound growth factor receptor of the erbB family and especially the
      epidermal growth factor receptor EGFR (erbB1) mediates resistance of tumor cells
      to both chemo- and radiotherapy when mutated or overexpressed. More recently a
      novel link between EGFR signaling pathways and DNA repair mechanisms, especially
      non-homologous end joining (NHEJ) repair could be demonstrated. The following
      review summarizes the current knowledge on the role of EGFR and its downstream
      signaling pathways in the regulation of cellular radiation response and DNA
      repair. CONCLUSION: The novel findings on radiation-induced EGFR-signaling and
      its involvement in regulating DNA-double strand break repair need further
      investigations of the detailed mechanisms involved. The results to be obtained
      may not only improve our knowledge on basic mechanisms of radiation
      sensitivity/resistance but also will promote translational approaches to test new
      strategies for clinically applicable molecular targeting.

PMID- 18058367
TI  - Pharmacological inhibition of EGFR tyrosine kinase affects ILK-mediated cellular
      radiosensitization in vitro.
AB  - PURPOSE: Integrin-linked kinase (ILK) mediates signals from beta integrins and
      links integrins to epidermal growth factor receptor (EGFR). Previous studies have
      identified an antisurvival effect of ILK in irradiated cells. The aim of this
      study was to evaluate the role of EGFR tyrosine kinase (tk) activity for ILK
      mediated radiosensitization. MATERIALS AND METHODS: Human FaDu squamous cell
      carcinoma (SCC) cells stably transfected with hyperactive ILK (ILK-hk) and
      ILK(fl/fl) and ILK(-/-) mouse fibroblasts were treated with the pharmacological
      EGFR-tk inhibitor BIBX1382BS without or in combination with single doses of X
      rays. Clonogenic radiation survival, protein expression and phosphorylation
      (EGFR, v-akt murine thymoma viral oncogene homolog 1 (Akt), p42/44 mitogen
      activated protein kinase), DNA-double strand break (DSB) repair measured by
      gammaH2AX foci, cell morphology and cell cycle distribution were examined.
      RESULTS: Expression of ILK-hk or ILK(fl/fl) status resulted in significant
      radiosensitization relative to vector controls or ILK(-/-). Following BIBX1382BS,
      clonogenic survival of normal fibroblasts and vector controls remained unaffected
      while ILK-hk-related radiosensitization was significantly diminished. In contrast
      to BIBX1382BS, which did not affect DNA-DSB repair, ILK-hk-mediated
      radiosensitization was associated with reduced DNA-DSB repair. At 10 days after
      BIBX1382BS treatment, FaDu transfectants, in contrast to fibroblasts, showed
      reduced cell size, accumulation of G1 phase cells and reduced Akt-serine(S)473
      phosphorylation. CONCLUSIONS: Our findings confirm ILK as a cell type-independent
      antisurvival factor in irradiated cells, which actions in terms of
      radiosensitization critically depend on proper EGFR-tk activity.

PMID- 18058368
TI  - New rationales for using TGFbeta inhibitors in radiotherapy.
AB  - PURPOSE: The first reports that ionizing radiation (IR) induces rapid and
      persistent activation of transforming growth factor beta1 (TGFbeta) were nearly
      two decades ago. Subsequent studies have shown that TGFbeta is a major mediator
      of cellular and tissue responses to IR and have revealed novel facets of its
      complex biology. RESULTS: We and others have recently shown that inhibition of
      production or signaling of TGFbeta in epithelial cells modulates radiosensitivity
      and impedes activation of the DNA damage response program. The primary transducer
      of cellular response to DNA damage caused by ionizing radiation is the nuclear
      protein kinase ataxia telangiectasia mutated, whose activity is severely
      compromised when TGFbeta is inhibited. Thus, in conjunction, with its well
      recognized contribution to normal tissue fibrosis, the role of TGFbeta in the
      genotoxic stress program provides a previously unsuspected avenue to modulate
      radiotherapy. CONCLUSIONS: We hypothesize that identification of the
      circumstances and tumors in which TGFbeta manipulation enhances tumor cell
      radiosensitivity, while protecting normal tissues, could significantly increase
      therapeutic index.

PMID- 18058369
TI  - Microenvironmental and genetic factors in haemopoietic radiation responses.
AB  - PURPOSE: To review studies of radiation responses in the haemopoietic system in
      the context of radiation-induced chromosomal instability, bystander effects, the
      influence of the microenvironment and genetic factors. CONCLUSIONS: Blood cells
      are continuously produced by the proliferation and differentiation of lineage
      specific precursor cells that, in turn, are all derived from a small population
      of multipotential stem cells. The homeostatic regulation of this hemopoietic
      hierarchy involves multiple regulatory factors and interactions with the tissue
      microenvironment and responses of the hemopoietic system are major determinants
      of outcome after exposure to ionizing radiation. A sub-optimal or aberrant
      response to radiation-induced damage may divert the system away from effective
      restoration of tissue homeostasis into responses that ultimately result in
      pathological changes. DNA damage in irradiated cells that has not been correctly
      restored by metabolic repair processes is conventionally regarded as the reason
      for the adverse consequences of radiation exposures. However, reports of
      radiation-induced genomic instability and radiation-induced bystander effects
      challenge this conventional paradigm. In the context of the haemopoietic system,
      these, so called, non-targeted effects can be inter-related and an instability
      phenotype need not necessarily be a reflection of genomically unstable cells but
      a reflection of responses to ongoing production of damaging bystander signals in
      the tissue microenvironment. Both the production of and the response to such
      signals are influenced by genetic factors and the cell interactions have
      properties in common with inflammatory mechanisms.

PMID- 18058370
TI  - Experimental anti-tumor therapy in 3-D: spheroids--old hat or new challenge?
AB  - PURPOSE: To give a state-of-the-art overview on the promise of three-dimensional
      (3-D) culture systems for anticancer drug development, with particular emphasis
      on multicellular tumor spheroids (MCTS). RESULTS AND CONCLUSIONS: Cell-based
      assays have become an integral component in many stages of routine anti-tumor
      drug testing. However, they are almost always based on homogenous monolayer or
      suspension cultures and thus represent a rather artificial cellular environment.
      3-D cultures--such as the well established spheroid culture system--better
      reflect the in vivo behavior of cells in tumor tissues and are increasingly
      recognized as valuable advanced tools for evaluating the efficacy of therapeutic
      intervention. The present article summarizes past and current applications and
      particularly discusses technological challenges, required improvements and recent
      progress with the use of the spheroid model in experimental therapeutics, as a
      basis for sophisticated drug/therapy screening. A brief overview is given
      focusing on the nomenclature of spherical 3-D cultures, their potential to mimic
      many aspects of the pathophysiological situation in tumors, and currently
      available protocols for culturing and analysis. A list of spheroid-forming
      epithelial cancer cell lines of different origin is provided and the recent trend
      to use spheroids for testing combination treatment strategies is highlighted.
      Finally, various spheroid co-culture approaches are presented that have been
      established to study heterologous cell interactions in solid tumors and thereby
      are able to reflect the cellular tumor environment with increasing accuracy. The
      intriguing observation that in order to retain certain tumor initiating cell
      properties, some primary tumor cell populations must be maintained exclusively in
      3-D culture is mentioned, adding a new but fascinating challenge for future
      therapeutic campaigns.

PMID- 18058371
TI  - Low dose radiation and intercellular induction of apoptosis: potential
      implications for the control of oncogenesis.
AB  - PURPOSE: This review is focused on the potential impact of low dose radiation
      effects on intercellular induction of apoptosis and the underlying reactive
      oxygen species (ROS)-mediated signaling pathways. RESULTS: Transformed cells are
      subject to ROS-mediated apoptosis induction by non-transformed cells
      ('intercellular induction of apoptosis') and by ROS-mediated autocrine self
      destruction. Sensitivity to intercellular induction of apoptosis and autocrine
      self-destruction are strictly correlated to the expression of the transformed
      state. Extracellular superoxide anions generated by transformed target cells
      drive the selectivity and sensitivity of this signaling system which is based on
      four different signaling pathways. Low dose irradiation of non-transformed cells
      enhances intercellular induction of apoptosis in transformed cells. This process
      is controlled by TGF-beta and seems to depend on the induction of peroxidase
      release. In addition, low dose radiation enhances superoxide anion generation of
      transformed target cells. CONCLUSIONS: Low dose radiation-triggered enhancement
      of intercellular induction of apoptosis and autocrine self-destruction might
      represent a potential control system during carcinogenesis. It might be the
      underlying mechanism for the well-known inhibitory effect of low dose radiation
      on detectable transformation events. However, modifications of the complex
      intercellular ROS-based signaling system may also lead to configurations in which
      low dose radiation attenuates ROS-mediated apoptosis induction.

PMID- 18058373
TI  - Statement of retraction.

PMID- 18058372
TI  - The impact of conventional and heavy ion irradiation on tumor cell migration in
      vitro.
AB  - PURPOSE: The influence of X-ray and (12)C heavy ion irradiation on tumor cell
      migration and of beta(3) and beta(1) integrin expression was investigated.
      MATERIAL AND METHODS: Two different tumor cell lines (U87 glioma and HCT116 colon
      carcinoma cells) were irradiated with 1, 3, or 10 Gy X-rays or (12)C heavy ions.
      24 h after irradiation a standardized Boyden Chamber assay for migration analysis
      was performed and cells were lysed for Western blotting. RESULTS: Radiation
      induced influences were cell line- and radiation type-dependent. X-rays decreased
      HCT116 migration at higher doses and appear to increase U87 migration after 3 Gy.
      Heavy ions decreased migration of both cell lines dose-dependently. A trend of
      increased beta(3) and beta(1) integrin expression in U87 cells after both
      radiation types was observed. beta(1) integrin expression in HCT116 cells was
      increased after X-rays but decreased after heavy ion irradiation. CONCLUSIONS:
      Results suggest that irradiation of tumor cells can modulate their migratory
      behavior. An increased migration, as shown with U87, leaves a higher probability
      of metastatic induction after irradiation of solid tumors in vivo, whereas an
      invariably reduced tumor cell migration, as shown after heavy ion treatment,
      could diminish the hazard of radiation-induced metastasis. As integrin expression
      and migration were only partially correlated, other migration-related surface
      molecules may be more relevant for radiation effects on tumor cell motility.

PMID- 18058374
TI  - Two new norbisabolane sesquiterpenoid glycosides from Glochidion coccineum.
AB  - Two new norbisabolane sesquiterpenoid glycosides, glochicoccinosides A (1) and B
      (2), together with two known compounds, have been isolated from the rhizomes of
      Glochidion coccineum. Their structures were elucidated by the combination of 1D
      NMR, 2D NMR, and MS spectral analysis, as well as chemical evidence. Cytotoxic
      activities and the antioxidant effect of these compounds were evaluated, but none
      of them showed activity.

PMID- 18058375
TI  - Saponins from the seeds of Achras sapota.
AB  - A new pentacyclic triterpenoid saponin (2) along with one known was isolated from
      the cotyledons of Achras sapota. Their structures were determined with the help
      of (1)H NMR, (13)C NMR and MS spectral data. The isolated compounds were named as
      3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-28-O-alpha-L
      rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-
      >2)-alpha-L-arabinopyranosyl protobassic acid (1) and 3-O-beta-D-glucopyranosyl
      (1-->3)-beta-D-glucopyranosyl-28-O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D
      xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl
      16alpha-hydroxy protobassic acid (2). Compound 2 showed antibacterial activity
      against Gram positive and negative bacteria.

PMID- 18058376
TI  - Flavonoids and ent-labdane diterpenoids from Andrographis paniculata and their
      antiplatelet aggregatory and vasorelaxing effects.
AB  - Two new flavones, designated as andropaniculosin A (1) and andropaniculoside A
      (2), and 30 known compounds were isolated as a result of detailed chemical
      examination on the whole plants of Andrographis paniculata. Their structures have
      been elucidated mainly by 1D and 2D NMR, and MS spectroscopic methods. Among
      them, four flavonoids showed potent inhibition of collagen, arachidonic acid,
      thrombin, and platelet activation factor induced platelet aggregation.
      Furthermore, a diterpenoid demonstrated moderate vasorelaxing effect in isolated
      rat thoracic aorta.

PMID- 18058377
TI  - Norsesquiterpenoid glucosides and a rhamnoside of pyrrolizidine alkaloid from
      Tephroseris kirilowii.
AB  - Four new glycosylated compounds have been isolated from the whole plant of
      Tephroseris kirilowii, including (-)-(1R,5R,6S,7R,8S)-8-O-beta-D
      glucopyranosyloxy-7-hydroxy-6-(2-hydroxypropan-2-yl)-9-methylenebicyclo[4.3.0]non
      3-one (tephroside A, 1), (-)-(1R,5R,6R,8R)-6-(2-O-beta-D-glucopyranosyloxypropan
      2-yl)-8-hydroxy-9-methylenebicyclo[4.3.0]non-3-one (tephroside B, 2), thesinine
      4'-O-alpha-L-rhamnoside (3), and p-coumaric acid 4-O-alpha-L-rhamnoside (4),
      together with the known roseoside. The structures of the new compounds were
      established by means of spectroscopic analysis.

PMID- 18058378
TI  - Dammarane triterpenes from Ligustrum lucidum.
AB  - Two new dammarane triterpenes 3beta-acetyl-20S,24R-dammarane-25-ene-24
      hydroperoxy-20-ol (1), 20S,24R-dammarane-25-ene-24-hydroperoxy-3beta,20-diol (2),
      as well as three known dammarane triterpenes, 3beta-acetyl-20S,25-epoxydammarane
      24alpha-ol (3), 20S,25-epoxydammarane-3beta,24alpha-diol (4), 20S-dammarane-23
      ene-3beta,20,25-triol (5) were isolated from the fruits of Ligustrum lucidum.
      Compounds 3-5 were isolated from the fruits of L. lucidum for the first time.
      Their structures were elucidated by spectroscopic methods.

PMID- 18058379
TI  - A triterpene saponin from Tribulus terrestris attenuates apoptosis in cardiocyte
      via activating PKC signalling transduction pathway.
AB  - The present study was conducted to examine the role of hecogenin-3-O-beta-D
      glucopyranosyl(1-->4)-beta-D-galactopyranoside (1), which is a triterpene saponin
      of Tribulus terrestris in cardiocytes during chemical hypoxia-ischaemia in vitro.
      Neonatal rat ventricular myocytes were isolated by collagenase digestion and
      treated with NaCN for 12 h. Cell apoptosis was defined by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) and flow
      cytometry. [Ca(2+)] was measured by confocal microscopy. There was a marked
      increase in the expression of the anti-apoptotic protein, Bcl-2, by NaCN. This
      change was increased by the saponin 1. PKCepsilon protein contents were increased
      in the cardiocyte membrane fraction in response to NaCN. PKCepsilon activation
      was augmented by the saponin 1. Inhibition of PKCepsilon with inhibitory peptide
      prevented Bcl-2 expression. Moreover, the saponin attenuated the apoptosis in
      cardiocyte in response to NaCN. It is therefore suggested that the saponin 1 may
      play a role in cardiocyte survival via PKCepsilon and Bcl-2.

PMID- 18058380
TI  - Irritant and cytotoxic coumarins from Angelica glauca Edgew roots.
AB  - Irritant and cytotoxic potentiality of six coumarins, isolated for the first time
      from the roots of Angelica glauca identified as 5,6,7-trimethoxycoumarin, 6
      methoxy-7,8-methylenedioxycoumarin, bergapten, decursinol angelate, decursin, and
      nodakenetin, were investigated. The irritant potential was explored by open mouse
      ear assay, evaluating their ID(50) after acute and by IU (Irritant units) after
      chronic effects, while the cytotoxic capability was explored by their LC(50),
      using brine shrimp (Artemia salina) larvae (nauplii). All the coumarins exhibited
      well-defined irritancy on mouse's ears, compared with the positive controlled
      euphorbium reaction and cytotoxic response against brine shrimp larvae, compared
      with the positive control colchicine. Decursinol angelate and decursin were the
      most potent and persistent irritant compounds with least ID(50), whose reactions
      lasted for 48 h. 6-Methoxy-7,8-methylenedioxycoumarin and bergaten revealed an
      intermediate irritant reactions, while 5,6,7-trimethoxycoumarin and nodakenetin
      displayed the least irritant and least persistent reactions on mouse ears. Both
      decursin and decursinol angelate also appeared to be the stronger cytotoxic
      agents than other coumarins. 5,6,7-trimethoxycoumarin displayed an intermediate
      cytotoxic behaviour, while other three coumarins, i.e., 6-methoxy-7,8
      methylenedioxycoumarin, bergapten, and nodakenetin, exhibited the least cytotoxic
      capacity against brine shrimp larvae.

PMID- 18058381
TI  - Metabolites of scutellarein in rat plasma.
AB  - The metabolism of scutellarein was investigated in rats. Four metabolites (M1-M4)
      together with scutellarein were detected and identified as scutellarein
      glucuronides in rat plasma by HPLC-DAD, HPLC-MS, and HPLC-MS/MS.

PMID- 18058382
TI  - Two new isoflavone triglycosides from the small branches of Sophora japonica.
AB  - Two new isoflavone triglycosides, genistein 4'-O-(6''-O-alpha-L-rhamnopyranosyl)
      beta-sophoroside (1), and genistein 4'-O-(6'''-O-alpha-L-rhamnopyranosyl)-beta
      sophoroside (2), together with five known compounds, namely, sophorabioside,
      genistin, rutin, quercetin 3-O-beta-D-glucopyranoside, and kaempferol 3-O-beta-D
      glucopyranoside, were isolated from the small branches of Sophora japonica L.
      Their structures were elucidated on the basis of spectroscopic analyses and
      chemical evidence.

PMID- 18058383
TI  - Two new triterpenoid saponins from the root of Ilex pubescens.
AB  - Two new triterpenoid saponins, named ilexsaponins B(4) (1) and C (2), have been
      isolated from the roots of Ilex pubescens. Their structures have been established
      as ilexgenin B 3-O-alpha-L-arabinopyranosyl-(2-->1)-beta-D-glucopyranosyl-(2-->1)
      beta-D-xylopyranoside (1) and 3-O-beta-D-xylopyranosyl spathodic acid 28-beta-D
      glucopyranosyl ester (2) by means of spectral and chemical methods.

PMID- 18058384
TI  - Oridonin induces human epidermoid carcinoma A431 cell apoptosis through tyrosine
      kinase and mitochondrial pathway.
AB  - Oridonin, a diterpenoid isolated from the plant Rabdosia rubescens, induces human
      epidermoid carcinoma A431 cell death through apoptosis and tyrosine kinase
      pathway. To examine the pathway of oridonin-induced A431 cell death, morphologic
      observation, lactate dehydrogenase activity-based assay, DNA agarose gel
      electrophoresis and Western blot analysis were carried out. When A431 cells,
      which overexpress epidermal growth factor receptor (EGFR), were treated with
      oridonin, caspase-3 was activated followed by the degradation of caspase-3
      substrates, inhibitor of caspase-activated DNase (ICAD) and poly(ADP-ribose)
      polymerase (PARP) in a time-dependent manner. Oridonin promoted the release of
      cytochrome c and the down-regulation of mitochondrial transmembrane potential
      (DeltaPsim). Oridonin up-regulated the expression ratio of mitochondrial
      proteins, Bax/Bcl-2. In addition, the total tyrosine kinase activity of A431
      cellular proteins and the expression of EGFR were markedly reduced after oridonin
      treatment. Taken together, oridonin induced apoptosis in A431 cells via
      mitochondrial pathway, activation of caspase-3 and inhibition of tyrosine kinase
      activities.

PMID- 18058385
TI  - Chemical constituents from Belamcanda chinensis.
AB  - One new flavone and one new isoflavone glycoside were isolated along with 15
      known compounds from the rhizome of Belamcanda chinensis (Iridaceae), and their
      structures were characterised as 5,4'-dihydroxy-6,7-methylenedioxy-3'
      methoxyflavone (1) and 3',5'-dimethoxy irisolone-4'-O-beta-D-glucoside (2) on the
      basis of spectroscopic methods.

PMID- 18058386
TI  - A novel oligosaccharide ester from Syringa pubescens.
AB  - Pubescenside A (1), a novel oligosaccharide ester, has been isolated from the
      flowers of Syringa pubescens, together with five known compounds D-mannitol (2),
      meso-inositol (3), hydrostytosol (4), glucose (5), and sucrose (6). The structure
      of 1 was elucidated as 1-O-[beta-D-glucopyranosyl-(1-6)-beta-D-galactopyranosyl
      (1-1)-beta-D-galactopyranosyl-6]-4,4-dimethylpelargonicate by chemical and
      spectroscopic means. The water extract of the flowers and leaves of S. pubescens
      showed cytotoxicity against L2215 cell line (IC(50)=78 microg/ml).

PMID- 18058387
TI  - Cognitive-behaviour therapy and skilled motor performance in adults with chronic
      tic disorder.
AB  - The first aim of the present study was to compare performance of people with tic
      disorders (TD) and controls on executive function and a range of skilled motor
      tests requiring complex performance, guided movements, hand co-ordination, and
      fine control of steadiness. The second aim was to investigate the effect of
      cognitive behaviour therapy (CBT) on motor performance. A total of 55 patients
      with TD were recruited at baseline from participants in a behavioural management
      programme. A comparison group of 55 patients suffering from a variety of habit
      disorders (HD) involving complex manual movements, were matched on age and level
      of education to 34 non-psychiatric controls. Participants were evaluated pre- and
      post-treatment and post-waitlist with a neuropsychological evaluation focusing on
      executive function (Wisconsin Card Sorting Test, WCST) and skilled motor
      performance (Purdue Pegboard, Hole Steadiness Test, and the Groove Test). Results
      revealed WCST scores in the normal range, while motor performance differed
      significantly on the Purdue Pegboard Tests in both TD and HD as compared to the
      control group. Cognitive-behavioural treatment selectively improved motor
      performance in both clinical groups compared to waitlist control, and this
      improvement related to clinical outcome measures.

PMID- 18058388
TI  - Memory systems involved in professional skills: a case of dense amnesia due to
      herpes simplex viral encephalitis.
AB  - JL, a 25-year-old physiotherapist, became densely amnesic following herpes
      simplex viral encephalitis (HSVE), causing bilateral damage to medial and ventral
      areas of her frontal and temporal lobes and their associated circuitry. Three
      years post-onset, her WAIS-R full scale IQ (Verbal 74, Performance 102) showed an
      estimated loss of +/- 50 points. She displayed severe global amnesia and markedly
      impaired social cognition. However, her immediate memory, perceptual priming, and
      cognitive problem-solving abilities were relatively spared. Her retention of
      professional skills was assessed using simulated physiotherapy scenarios. JL was
      able to demonstrate some procedural skills spontaneously, but was unable to apply
      them precisely and flexibly to individual patient needs. She showed no memory of
      theoretical or propositional physiotherapy knowledge, and could neither plan
      treatment nor reason clinically. Her performance was well below that of four
      other physiotherapists who had also not practised for 4 years. Thus, despite the
      relative sparing of her implicit memory, JL's performance lacked the co-ordinated
      operation of declarative and implicit long-term memory and the links to working
      memory that are necessary for the flexible performance of complex professional
      procedures.

PMID- 18058389
TI  - Neurobehavioural treatment for obsessive-compulsive disorder in an adult with
      traumatic brain injury.
AB  - Although obsessive-compulsive disorder has been reported as one of many anxiety
      related sequelae of brain injury, few empirical data of its responsiveness to
      psychological intervention are available. In this study, a single participant
      changing criterion experimental design was used to evaluate a neurobehavioural
      intervention for compulsive behaviour of an adult with severe traumatic brain
      injury. The participant, a man aged 24 years, had sustained frontal-temporal lobe
      brain trauma 12 months earlier, and presented with compulsive counting and
      voiding of bladder. The neurobehavioural intervention consisted of regular in
      home consultations, self-regulation procedures including self-recording of
      compulsive behaviour, stress-coping strategies, errorless remediation, social
      reinforcement, and gradual fading of intervention. Baseline showed counting
      occurred on average 80% of daily hourly intervals, and voiding 12 times per day.
      Intervention produced elimination of compulsive counting, acceptable voiding at 8
      times per day, and reports of the participant's satisfaction with intervention
      methods and outcomes. At 6 months follow-up, counting remained at zero levels,
      and voiding had decreased further to 7 times per day.

PMID- 18058390
TI  - Care arrangements, grief and psychological problems among children orphaned by
      AIDS in China.
AB  - The China Ministry of Health has estimated that there are at least 100,000 AIDS
      orphans in China. The UNICEF China Office estimates that between 150,000 and
      250,000 additional children will be orphaned by AIDS over the next five years.
      However, limited data are available regarding the sociodemographic
      characteristics, care arrangements, barriers to appropriate grief resolution and
      psychological problems among AIDS orphans in China. In this article, we review
      secondary data and reports from scientific literature, government, non
      governmental organisations and public media regarding children orphaned by AIDS
      in China to address their living situation, bereavement process and psychological
      problems. Our review suggests that AIDS orphans in China are living in a
      stressful environment, with many orphans struggling with psychological problems
      and unmet basic needs such as food, shelter, education and medical care. Based on
      our review, we suggest that future studies should address the psychosocial needs
      of AIDS orphans in China and develop health promotion programmes to mitigate the
      negative impact of parental death on the physical and psychosocial well-being of
      these orphans.

PMID- 18058391
TI  - Childhood abuse and initial presentation for HIV care: an opportunity for early
      intervention.
AB  - An alarmingly high prevalence of childhood sexual and physical abuse has been
      observed in HIV-infected men and women, with rates several times higher than
      observed in the general population. Childhood abuse history has been associated
      with worse antiretroviral adherence and negative health behaviours in HIV
      infected patients. This study evaluates the relationship between childhood abuse
      and the timing of presentation for HIV care. Participants in a multi-center
      prospective cohort study, who established initial HIV care after January 1996 and
      had a CD4 count available within six months of initial presentation, were
      included in this analysis. Bivariate contingency tables and multivariate logistic
      regression were used to evaluate the association of childhood abuse with early
      presentation for HIV care (initial CD4 count > or =200/mm3). Among the 186
      subjects included in this analysis, 33% had childhood abuse histories and 58% had
      an initial CD4 count > or =200/mm3. Participants with a history of childhood
      abuse were more likely to present early for HIV care (AOR=2.12; p=0.03), perhaps
      because survivors of abuse tend to have higher utilization of health services.
      Because HIV-infected patients with childhood abuse histories have worse
      antiretroviral medication adherence and are more likely to engage in high-risk
      sexual and injection drug use behaviours, early presentation affords clinicians
      the opportunity for timely institution of interventions that may improve patient
      outcomes and prevent secondary HIV infections.

PMID- 18058392
TI  - The influence of disclosure of HIV diagnosis on time to disease progression in a
      cohort of Romanian children and teens.
AB  - The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that in 2004,
      there were 39.4 million people living with HIV/AIDS worldwide (UNAIDS/WHO Report
      on the global HIV/AIDS epidemic, 2004). Children less than 15 years of age
      comprise 2.2 million of these individuals. As more children globally gain access
      to highly active antiretroviral therapy (HAART), more children are growing to the
      age when disclosure of their HIV status is inevitable. This information may
      affect a child's disease trajectory, and in the context of HAART, may have wide
      ranging impact in the management of paediatric HIV infection. This study is an
      investigation of the effect of disclosure of a child's own HIV infection status
      on death and CD4 decline in a cohort of 325 HIV-infected Romanian children
      receiving highly active antiretroviral therapy (HAART). A retrospective database
      analysis was conducted. Data from a nearly three-year period were examined.
      Children who were aware of their HIV diagnosis were compared with those who were
      not aware. We found significant associations between not knowing the HIV
      diagnosis and death, and not knowing the HIV diagnosis and disease progression
      defined as either death or CD4 decline. Our results imply that in the context of
      HAART, knowledge of one's own HIV infection status is associated with delayed HIV
      disease progression.

PMID- 18058393
TI  - Feelings related to motherhood among women living with HIV in Brazil: a
      qualitative study.
AB  - A qualitative study was carried out with 12 HIV-positive women to describe their
      feelings about motherhood, to learn whether they make plans for the care of their
      children, and to identify mechanisms of defence they use to face their
      seropositivity. Motherhood was seen as an essential attribute of women and a
      reason of living. Breastfeeding was considered a fundamental component of the
      maternal role. Some women made provisions with their family for the care of their
      children. Thinking about the possibility of their children becoming orphans made
      women feel impotent and guilty. Such painful feelings were minimized through
      mechanisms of defence like compensation, denial, rationalization and projection.
      Health care professionals should consider that clinical assistance and free
      distribution of medication are not sufficient to HIV-positive women. These women
      need continuous support and guidance with respect to their physical, mental and
      emotional health as well as that of their children.

PMID- 18058394
TI  - Infant feeding practices: realities and mind sets of mothers in Southern Africa.
AB  - Exclusively breastfed infants in developing countries are at lower risk of HIV
      transmission than mixed-fed infants. Ethno-graphic research was conducted in
      eleven low-resource settings across South Africa, Namibia and Swaziland to
      understand how the perceptions and experiences of counselling health workers,
      pregnant women and recent mothers could be used to improve infant feeding
      counselling. Despite prevention of mother-to-child transmission (PMTCT)
      programmes, very early mixed-feeding remains the norm; traditional
      conceptualisations of 'water as life' and 'milk as a fluid' are holding up
      against current PMTCT education, with milk considered liquid 'drink' rather than
      'real food'. This aggravates an 'insufficient milk syndrome' where disempowered
      mothers perceive their breastmilk, and themselves, as deficient - 'not good
      enough'. Infant feeding is embedded within traditional relationships of intimacy;
      both relatives and breadwinner have influence and even authority over options and
      modes of infant feeding. In patriarchal and violent societies, traditional power
      differentials prohibit easy or complete HIV disclosure or condom negotiation; HIV
      status remains hidden from most partners and relatives. This context of secrecy
      means that the traditional advice and authority, which the mothers feel they dare
      not disregard, is often blind to the mother and her infant's HIV status and
      survival needs.

PMID- 18058395
TI  - What should South African HIV vaccine trials do about social harms?
AB  - Phase I and II HIV vaccine trials are currently underway in South Africa. Sites
      are being prepared for Phase III vaccine trials. Participants in these trials
      risk exposure to 'social harms' that may impact on participant enrolment and
      retention and threaten their welfare. Potential social harms should be prevented,
      minimised and/or addressed. This paper examines the literature on potential
      social harms in HIV vaccine trials. It outlines the type and severity and
      frequency of potential social harms and ways these have been monitored in
      settings in the developed world and Thailand. We argue that many of these social
      harms are likely to manifest in South African trials, however, it is also likely
      social harms may manifest differently in our setting, such as domestic violence.
      Therefore careful formative research is required to identify what constitutes a
      social harm in our setting. Measures should be carefully tailored to record such
      events and methods established to prevent or address these.

PMID- 18058396
TI  - A model of integrated primary care for HIV-positive patients with underlying
      substance use and mental illness.
AB  - There is a high burden of underlying substance use and mental illness in HIV
      infected populations. HIV-care settings provide an important opportunity to
      assess substance and mental health needs among HIV-positive patients and to
      provide or make referrals for appropriate treatment services. In 2003, with
      funding from the Center for Substance Abuse Treatment (CSAT), we developed a
      model of integrated substance-use counselling and referral for treatment within a
      primary care HIV-care setting at The Miriam Hospital in Providence, Rhode Island.
      The project uses a multidisciplinary approach to provide linkage to treatment
      services for substance use and mental illness as well as to help participants
      with social service needs, such as housing and medical coverage, to ensure
      continuity of care and optimal HIV treatment adherence. Twelve percent of the 965
      HIV-infected patients in care at our center have been enrolled in the project. Of
      these, all have a current substance-use disorder and 79.3% have been diagnosed
      with a mental illness. In addition, most participants are hepatitis C-positive
      (HCV) (65.5%). The majority of participants are on antiretroviral therapy
      (76.7%). Participants have been referred for the following treatment modalities:
      intensive outpatient services, methadone, buprenorphine, outpatient services and
      residential as well as individual and group counselling. Our model has been
      successful in assessing the substance-use and mental health needs of HIV-infected
      individuals with numerous co-morbidities and referring them for ancillary medical
      and social services.

PMID- 18058397
TI  - The impact of illicit drug use and substance abuse treatment on adherence to
      HAART.
AB  - High levels of adherence to highly active antiretroviral therapy (HAART) are
      essential for virologic suppression and longer survival in patients with HIV. We
      examined the effects of substance abuse treatment, current versus former
      substance use, and hazardous/binge drinking on adherence to HAART. During 2003,
      659 HIV patients on HAART in primary care were interviewed. Adherence was defined
      as > or =95% adherence to all antiretroviral medications. Current substance users
      used illicit drugs and/or hazardous/binge drinking within the past six months,
      while former users had not used substances for at least six months. Logistic
      regression analyses of adherence to HAART included demographic, clinical and
      substance abuse variables. Sixty-seven percent of the sample reported 95%
      adherence or greater. However, current users (60%) were significantly less likely
      to be adherent than former (68%) or never users (77%). In multivariate analysis,
      former users in substance abuse treatment were as adherent to HAART as never
      users (Adjusted Odds Ratio (AOR)=0.82; p>0.5). In contrast, former users who had
      not received recent substance abuse treatment were significantly less adherent
      than never users (AOR=0.61; p=0.05). Current substance users were significantly
      less adherent than never users, regardless of substance abuse treatment (p<0.01).
      Substance abuse treatment interacts with current versus former drug use status to
      affect adherence to HAART. Substance abuse treatment may improve HAART adherence
      for former substance users.

PMID- 18058398
TI  - Development and psychometric validation of the HIV Treatment Knowledge Scale.
AB  - Accurate treatment knowledge is required for patients to successfully manage
      complex medical conditions. Existing HIV knowledge scales focus on disease
      transmission and risk factors. This is the first study to develop and validate a
      scale to measure HIV treatment knowledge about complex treatment issues such as
      adherence, side-effects and drug resistance. A total of 346 participants were
      recruited into this cross-sectional study. Participants included HIV-positive
      patients (n=130), HIV-hepatitis C co-infected patients (n=22), hepatitis C
      patients, (n=78), community healthcare providers (n=35) and college students
      (n=81). Participants completed the proposed HIV Treatment Knowledge Scale and a
      validated measure of general knowledge about HIV transmission and risk factors.
      Two-week test-retest data were collected. Results demonstrated that the HIV
      Treatment Knowledge Scale was significantly correlated with general HIV knowledge
      across all samples. Among HIV-positive patients, the HIV Treatment Knowledge
      Scale was positively associated with time since HIV diagnosis. HAART-experienced
      patients had significantly higher treatment knowledge than HAART-naive patients.
      HIV-positive patients scored significantly higher than hepatitis C patients and
      college students on HIV treatment knowledge. Test-retest reliability (r=0.83) and
      internal consistency (reliability coefficient=0.90) were both satisfactory. The
      HIV Treatment Knowledge Scale is a novel, easy-to-administer measure
      demonstrating high levels of validity and reliability. It has important
      applications as a clinical teaching tool with patients and healthcare workers and
      it could be used as an outcome indicator in HIV educational intervention studies.

PMID- 18058399
TI  - Subjective memory complaints of Chinese HIV-infected patients in Hong Kong:
      relationships with social support, depressive mood and medical symptoms.
AB  - The present study aimed at investigating the contribution of social support,
      depressive mood, medical symptoms and objective memory performance to the
      subjective memory complaints of Chinese HIV-infected persons in Hong Kong. Ninety
      HIV-infected persons were administered the Hong Kong List Learning Test (HKLLT)
      as an objective measure of memory. They also reported their subjective memory
      complaints, HIV-related medical symptoms, depressive mood and perceived social
      support by self-administered questionnaires. Path analyses were conducted to
      evaluate models that depicted the relationships among the variables. The final
      model that showed the best fit to the data suggested that objective memory
      performance had no significant role to play in patients' subjective memory
      complaints. Depressive mood was found to be a significant factor that directly
      affected patient's subjective memory complaints and social support played an
      indirect role with depressive mood as a mediating variable. These findings
      suggest that memory complaints might be an indicator of mood disturbance and
      social support might be useful in ameliorating depressive mood and these
      complaints. The need of assessment of other cognitive functions in future
      research is also discussed.

PMID- 18058400
TI  - A community participation intervention to reduce HIV/AIDS stigma, Nakhon
      Ratchasima province, northeast Thailand.
AB  - This paper explores HIV/AIDS stigma in the socio-cultural context of Nakhon
      Ratchasima Province in the northeastern region of Thailand. Action research was
      used to develop a community participation intervention. The intervention was
      implemented in one village over a period of eight months. We describe the
      intervention and then test its effect on HIV/AIDS knowledge and HIV/AIDS stigma
      using a non-equivalent pre-test-post-test control group design. Analysis of co
      variance confirms that, controlling for initial levels of HIV/AIDS knowledge and
      stigma, the intervention had a significant effect on HIV/AIDS knowledge score
      (p<0.01) and HIV/AIDS stigma score (p<0.01). Participatory observations by the
      researchers on villagers' perceptions and behaviour were consistent with the
      quantitative results. These results suggest that community interventions which
      empower the community, combined with a financial contribution to reduce resource
      constraints, are a useful and effective means of increasing interaction between
      people living with HIV/AIDS (PLWHA) and other community members, increasing
      tolerance and reducing HIV/AIDS stigma.

PMID- 18058401
TI  - Clinic appointment attendance for sexually transmitted infection screening among
      Filipina sex workers: a multilevel analysis.
AB  - This study evaluates putative individual- and contextual-level social risk
      factors that may influence the likelihood that Filipina female sex workers (FSWs)
      attend and utilize health services for STI screening. Face-to-face interviews
      were conducted with 1004 FSWs and their 86 employers. Research staff also
      collected clinic appointment attendance data. Hierarchical linear modelling was
      used to estimate the simultaneous effects of individual- and workplace-level
      factors. Results showed that both individual- and contextual-level
      characteristics were associated with STI screening appointment attendance.
      Individual characteristics found to have significant effects on clinic attendance
      included occupation, income, length of work and commercial sex involvement. City
      of establishment was a workplace characteristic significantly associated with
      appointment attendance. In addition to cross-level interactions, the impact of
      individual-level occupation depended upon characteristics of the workplace. These
      findings suggest that individual health service utilization is contingent upon
      contextual-level risk factors in the workplace. Intervention implications aimed
      at increasing clinic attendance are discussed.

PMID- 18058402
TI  - HIV infection dynamics in rural Andhra Pradesh south India: a sexual-network
      analysis exploratory study.
AB  - The southern state of Andhra Pradesh (AP) has one of the highest rates of HIV-1
      infection in India. Estimates of HIV infection in rural areas have begun to
      approximate the urban. Methods of HIV transmission in rural India are poorly
      understood. We examined risk factors for HIV transmission in a group of rural
      villages in AP through the use of a sexual-network analysis survey - the Indian
      Health and Family Life Survey (IHFLS). The study sample included 20 HIV-positive
      and 40 HIV-negative matched controls randomly selected from a population-based,
      voluntary counselling and testing program in rural AP. HIV-1 status was confirmed
      by Western Blot. The 405-item IHFLS is based upon the National Health and Life
      Survey which has been validated in the US and China. The sample mean age was 37
      years and 22% were of a tribal caste. Among female respondents, none were
      commercial sex workers (CSWs) and there were no significant social or behavioral
      associations with HIV infection. Among male respondents, ever having bought sex
      and having more than one lifetime partner were found to be significantly
      associated with HIV infection (p=0.002 and p=0.017). Amongst sub-populations, all
      men who had sex with men (MSM) were married. Tribals were more likely to report a
      concurrent sexual relationship (p=0.04). All high-risk men, including MSM, men
      who buy sex and men with multiple lifetime female partners did not use condoms.
      Public health interventions aimed at reducing HIV transmission in rural AP should
      consider targeting sub-populations of men who engage in covert MSM or CSW, high
      risk tribal caste members and at-risk wives.

PMID- 18058403
TI  - Gender differences in condom use prediction with Theory of Reasoned Action and
      Planned Behaviour: the role of self-efficacy and control.
AB  - There is much evidence that demonstrates that programs and interventions based on
      the theoretical models of the Theory of Reasoned Action (TRA) and the Theory of
      Planned Behaviour (TPB) have been effective in the prevention of the sexual
      transmission of HIV. The objective of this work is to compare the effectiveness
      of both models in the prediction of condom use, distinguishing two components
      inside the variable Perceived Behavioural Control of the TPB model: self-efficacy
      and control. The perspective of gender differences is also added. The study was
      carried out in a sample of 601 Portuguese and Spanish university students. The
      results show that the females have a higher average in all the TPB variables than
      males, except in the frequency of condom use: females request the use of condoms
      less frequently than males. On the other hand, for both females and males the TPB
      model predicts better condom-use intention than the TRA. However there are no
      differences between the two models in relation to the prediction of condom-use
      behaviour. For prediction of intention, the most outstanding variable among
      females is attitude, while among males they are subjective norm and self
      efficacy. Finally, we analyze the implications of these data from a theoretical
      and practical point of view.

PMID- 18058404
TI  - Internet use among low-income persons recently diagnosed with HIV infection.
AB  - Patients are increasingly using the Internet to obtain health-related
      information, communicate with providers and access research. Use of the Internet
      to obtain health-related information by low-income patients recently diagnosed
      with HIV infection has not been examined. In 2005, we surveyed 126 low-income
      patients diagnosed with HIV infection within the last three years. Eighty-five
      percent of the patients were<50 years old, 63% were male, 68% were minority race,
      27% were Hispanic and 61% acquired HIV through heterosexual intercourse. Twenty
      eight percent never completed high school and 74% earned<$15,000 in 2004. While
      89% indicated they would like to use the Internet to access information about
      HIV, 52% had never used the Internet, 28% had never used it to obtain health
      related information and only 18% had done so at least monthly for the last six
      months. Two-thirds of the population studied would need instruction on how to use
      the Internet. In multivariable regression, 2004 income > or =$15,000 predicted
      monthly Internet use to obtain health-related information. Older age,
      heterosexual intercourse as HIV risk factor and inadequate health literacy were
      independent predictors of needing instruction. The low-income population with HIV
      infection lags behind the general population in Internet access and may not
      benefit from Internet-dependent advances in health communication, including HIV
      related interventions.

PMID- 18058406
TI  - Childhood sexual and physical abuse histories, PTSD, depression, and HIV risk
      outcomes in women injection drug users: a potential mediating pathway.
AB  - We explored links between childhood sexual abuse (CSA), childhood physical abuse
      (CPA), posttraumatic stress disorder (PTSD)/depression, and women injection drug
      users' (IDUs') risk in 113 women recruited from two syringe exchange sites. More
      than half (56%) reported CSA, 68% CPA, 23% likely were depressed-only, and 53%
      likely had PTSD/depression. CSA was associated with sexual (p = 0.003) and drug
      risk (p = 0.05); CPA was not. CSA was associated with PTSD/depression (p = 0.03);
      PTSD/depression was associated with sexual (p < 0.01) and drug (p < 0.03) risk.
      After PTSD/depression adjustment, CSA was no longer associated with sexual or
      drug risk. These results suggest that women IDUs' CSA-to-risk path is mediated by
      PTSD/depression.

PMID- 18058407
TI  - Differences in early onset alcohol use and heavy drinking among persons with
      childhood and adulthood trauma.
AB  - We examined predictors for age at onset of first alcohol use and onset of
      heaviest alcohol use among men (n = 43) and women (n = 46) with alcohol
      dependence and PTSD, PTSD only, alcohol dependence only, and controls, with a
      particular focus on individuals with child versus adult trauma. Using analysis of
      variance procedures, results showed differences in onset of first alcohol use and
      heaviest drinking between childhood and adulthood trauma victims. These
      preliminary results indicate that behavioral mechanisms associated with alcohol
      use patterns between individuals with childhood and adulthood trauma are
      dissimilar, suggesting greater psychopathological consequences for individuals
      with childhood trauma.

PMID- 18058408
TI  - The impact of personality disorders on alcohol-use outcomes in a pharmacotherapy
      trial for alcohol dependence and comorbid Axis I disorders.
AB  - Although antisocial and borderline personality disorders frequently co-occur with
      alcohol dependence and other Axis I disorders, their effect on alcohol use
      outcomes in context of pharmacotherapy remains unclear. Patients with Major Axis
      I disorders, including alcohol dependence, and diagnosis of antisocial (ASPD) or
      borderline personality disorder (BPD) were enrolled in a 12-week medication trial
      for treatment of their alcohol dependence. Everyone was randomized to one of four
      cells: naltrexone alone, placebo alone, open label disulfiram and naltrexone, or
      open label disulfiram and placebo. Outcome measures included scales for alcohol
      use and craving. Data were analyzed comparing patients with ASPD vs. those
      without, and patients with BPD vs. those without. Diagnosis of personality
      disorder did not adversely affect alcohol outcomes, and patients with ASPD or BPD
      did not have a poorer response to medication than patients without diagnosis of
      ASPD or BPD. The findings suggest that naltrexone and disulfiram can be safely
      and effectively used with patients who have comorbid diagnoses of Axis I and Axis
      II disorders.

PMID- 18058409
TI  - Pathways to nicotine dependence in African American and Puerto Rican young
      adults.
AB  - This investigation examined the pathways to nicotine dependence among a sample of
      inner city African-American and Puerto Rican young adults (mean age = 26.1 years,
      SD = 1.4 years). Four hundred and seventy-five young adults were interviewed. The
      findings based on structural equation models showed that family conflicts,
      parental tobacco use, and weak ethnic identity were associated with vulnerable
      personality attributes and drug use, which in turn were related to nicotine
      dependence. Prevention strategies in young adults aimed at family conflicts,
      parental tobacco use, vulnerable personality attributes, drug use, weak ethnic
      identity, and socioeconomic status should be effective in reducing risks for
      nicotine dependence.

PMID- 18058411
TI  - Withdrawal symptoms do not predict relapse among subjects treated for cannabis
      dependence.
AB  - This is the first follow-up study on the association between cannabis withdrawal
      symptoms and risk of relapse to cannabis use. Withdrawal symptoms were assessed
      in 36 subjects seeking treatment for cannabis dependence. All were free of other
      substance use or alcohol abuse in the month before abstinence from cannabis.
      Follow-up was performed 26+/-4 months later, and at this point, the withdrawal
      symptoms were re-assessed. The following symptoms were significantly elevated
      after abstinence compared with follow-up: irritability, anger, depression,
      restlessness, craving, sleep problems, strange dreams, increased appetite,
      violent outbursts, sweating, hot flashes, chills, and shakiness. This offers
      further validation of a cannabis withdrawal syndrome. Average withdrawal scores
      at baseline did not differ with gender, age, treatment type, extent of cannabis
      use, or a lifetime history of anxiety or affective disorders. Withdrawal scores
      at baseline did not predict relapse during follow-up.

PMID- 18058410
TI  - Clinic variation in the cost-effectiveness of contingency management.
AB  - This study determined whether, and by how much, the cost-effectiveness of
      contingency management (CM) varied across the eight clinics in the National
      Institute on Drug Abuse Clinical Trials Network MIEDAR trial. Incremental costs,
      incremental outcomes, and incremental cost-effectiveness ratios (ICERs) of CM
      compared to usual care were calculated, compared and contrasted for each of the
      clinics. Results showed that the incremental cost of using CM compared to usual
      care varied by a factor of 1.9 across the clinics, ranging from an additional
      $306 to an additional $582 per patient. The effect of CM on the longest duration
      of continuous stimulant abstinence (LDA) varied by a factor of 8.0 across the
      clinics, ranging from an additional 0.5 to an additional 4.0 weeks. The ICERs for
      the LDA varied by a factor of 4.6 across the clinics, ranging from $145 to $666.
      These results show that the cost-effectiveness of CM varied widely among the
      clinics in the MIEDAR trial. Future research should focus on identifying the
      sources of this variation, perhaps by identifying clinic-level best practices
      and/or identifying those subgroups of patients that respond the most cost
      effectively, with the ultimate goal of improving the cost-effectiveness of CM
      overall.

PMID- 18058412
TI  - Combining cognitive behavioral therapy with contingency management for smoking
      cessation in adolescent smokers: a preliminary comparison of two different CBT
      formats.
AB  - This pilot study evaluated the optimal format of cognitive behavioral therapy
      (CBT) to combine with contingency management (CM) in a four-week, high school
      based smoking cessation program. Thirty-four adolescent smokers received a
      standard weekly version of CBT or a frequent brief behavioral intervention.
      Results indicate a trend toward a higher seven-day point prevalence end-of
      treatment abstinence rate and percent days abstinent during treatment in the CBT
      condition. In addition, significantly more participants in the CBT group
      completed treatment. These preliminary results suggest that when combined with
      CM, the standard weekly format of CBT is more acceptable to adolescent smokers.

PMID- 18058413
TI  - The CAGE as a measure of hazardous drinking in the homeless.
AB  - The aim of this study was to test the validity of the CAGE questions as a measure
      of severe drinking in subjects at drop-in centers for the homeless, using
      biological markers of acute liver reaction to alcohol as the "gold standard." A
      sample of homeless men and women in Copenhagen were invited to participate in a
      study of health problems. Subjects were interviewed and blood samples were taken
      and screened for indicators of liver dysfunction (gamma-glutamyltransferase
      [gammaGT], mean corpuscular volume [MCV], alanine aminotransferase [ALAT], and
      alkaline phosphatase [Alpase]), and hepatitis C [HCV]. Scores on CAGE correlated
      strongly with years of heavy drinking (rho = 0.43, p < 0.001), and while years of
      drinking did not correlate with biomarkers after controlling for multiple
      hypothesis testing, CAGE correlated with gammaGT, Alpase and ALAT, but not MCV.
      The correlations held even among those without HCV, but subjects with HCV + and
      CAGE > 1 had quite extreme values on liver markers. Findings suggested that the
      CAGE was able to identify homeless drinkers whose drinking was significantly
      associated with increases in biomarkers associated with heavy drinking.

PMID- 18058414
TI  - Searching the Internet for drug-related web sites: analysis of online available
      information on ecstasy (MDMA).
AB  - Although the Internet is a growing source of information on MDMA/ecstasy, no
      studies so far have investigated the level and quality of ecstasy information
      available to the typical Web user. In the present study, 280 Web sites were
      identified and analyzed; 50.4% had an anti-drug approach, 16.2% a harm reduction
      approach, and 24.8% a pro-drug approach. MDMA pro-drug Web sites appeared
      significantly earlier in the search engines' results list than both anti-drug and
      harm reduction Web sites (F (3; 159) = 3.288; p = .022). This study represents
      the first systematic analysis of information available online on ecstasy.
      Implications for further research are discussed.

PMID- 18058415
TI  - Assessment of club drug use in a treatment-seeking sample of individuals with
      marijuana dependence.
AB  - Club drug use is becoming increasingly popular in the United States and has been
      associated with chronic psychiatric symptoms and neuropsychological
      abnormalities. Patterns of club drug use and characteristics of club drug users
      are not homogeneous. Thus, treatment-seeking marijuana-dependent individuals may
      have a differential pattern of club drug use. Baseline assessments collected from
      55 individuals participating in a pharmacological treatment study for marijuana
      dependence were examined. Individuals completed a 16-item self-report
      questionnaire assessing club drugs used, frequency and patterns of use, problems
      associated with use, and reasons for use. Subjects were primarily male (87.3%)
      and Caucasian (81.8%), with a mean age of 32.1 (+/-9.1 years). As expected, a
      large number of individuals had used ecstasy (75%). However, LSD and
      methamphetamine use was also reported by many users (82.5% and 47.5%
      respectively), with many individuals reporting the use of more than one club
      drug. Notably, 31.6% of individuals reported tolerance to club drugs. These
      results emphasize the significant co-occurrence of club drug use in marijuana
      dependent individuals. This appears to be the first study to report on club drug
      use in treatment-seeking marijuana-dependent individuals. Clinical implications
      and directions for future research are discussed.

PMID- 18058416
TI  - Factors associated with altered pharmacokinetics in substance users and non
      substance users receiving lopinavir and atazanavir.
AB  - Substance use is highly prevalent in HIV-infected individuals in the United
      States, and clinical management is complicated by the need for antiretroviral
      treatment, addiction therapy, variable medication adherence, and co-morbidities.
      The interrelation between HIV and substance use prompted our investigation to
      examine substance use and self-reported medication adherence in patients
      receiving the HIV-1 protease inhibitors, atazanavir (ATV) or lopinavir (LPV). ATV
      and LPV pharmacokinetics were determined by measuring plasma concentrations in
      subjects with active substance use (SU group) or with no active substance use
      (NSU group). No difference in adherence was observed between groups (p > 0.05).
      The mean SU ATV trough was 0.550+/-0.45 microg/mL; the mean NSU ATV trough was
      0.780+/-0.590 microg/mL (p > 0.05). The mean SU LPV trough was 4.02+/-2.39
      microg/mL; the mean NSU LPV trough was 6.67+/-0.910 microg/mL (p = 0.01). Co
      factors found to be associated with variation in ATV and LPV concentrations
      included concurrent methadone use, cigarette smoking, and substance use status.
      These data indicate that chronic HIV treatment may be assisted with plasma
      concentration monitoring to identify those patients who may require dosage
      modification and/or regimen adjustment in order to optimize antiretroviral
      effects.

PMID- 18058417
TI  - Telephone enhancement of long-term engagement (TELE) in continuing care for
      substance abuse treatment: a NIDA clinical trials network (CTN) study.
AB  - The TELE study examined the feasibility and potential efficacy of phone calls to
      patients after discharge from short- term inpatient and residential substance
      abuse treatment programs to encourage compliance with continuing care plans.
      After review of their continuing care plans, 339 patients from four programs were
      randomized either to receive calls or to have no planned contact. Ninety-two
      percent of patients randomized to receive calls received at least one call. No
      difference was found between groups in self-reported attendance at one or more
      outpatient counseling sessions after discharge (p = .89). When program records of
      all participants were examined, those receiving calls had a greater likelihood of
      documented attendance (48%) than those not called (37%). Results were not
      statistically significant (p < .003) because of the Hochberg correction for
      multiple tests. While the phone calls were feasible, the lack of clear evidence
      of efficacy of the calls suggests the need for further investigation of the role
      of telephone intervention to encourage compliance and improve outcomes.

PMID- 18058418
TI  - Assessing negative consequences in patients with substance use and bipolar
      disorders: psychometric properties of the short inventory of problems (SIP).
AB  - The Short Inventory of Problems (SIP), a questionnaire that measures negative
      consequences of alcohol use, has not been validated among substance users with co
      occurring psychiatric illness. This study examined the psychometric properties of
      the SIP in 57 outpatients diagnosed with substance use disorder and bipolar
      disorder. We modified the items to assess drugs in addition to alcohol and,
      further, we added corresponding items to assess consequences of bipolar disorder.
      This modified version of the SIP was psychometrically sound, and may be useful in
      patients with both disorders. A greater understanding of perceived negative
      consequences may enhance outcome assessment in dually diagnosed populations.

PMID- 18058419
TI  - Impact of substance abuse treatment on arrests among opiate users in Washington
      State.
AB  - Administrative data from Washington State's Division of Alcohol and Substance
      Abuse drive this three-year prospective study of the impact of substance abuse
      treatment on arrests among 12,962 opiate users receiving publicly funded
      substance abuse services. Using survival analysis, the risk of arrest among
      opiate users who receive substance abuse treatment is compared to those who do
      not receive treatment. Propensity scores control for client characteristics
      associated with admission to substance abuse treatment. Overall, a reduction in
      the risk of arrest was found among subjects in treatment (Hazard Ratio = 0.59
      0.78, p < .05) and subjects successfully completing treatment (Hazard Ratio =
      0.75, p < .05). Risk of arrest was elevated among those with a negative outcome
      to treatment (Hazard Ratio = 1.23, p < .05).

PMID- 18058420
TI  - Perception of smoking-related health consequences among pregnant and non-pregnant
      women.
AB  - The objective was to examine the perception of smoking-related health
      consequences and its relationship to pregnancy and intent to quit. Over a two
      week period, pregnant and non-pregnant women, intending and not intending to quit
      smoking, rated the probability for smoking-related health consequences to occur,
      given continuing to smoke and quitting smoking. Pregnant women who did not intend
      to quit smoking exhibited the lowest estimated probability for the smoking
      related health consequences to occur if they continued smoking. For all women,
      there was a statistically significant estimated effect of quitting smoking.
      Renewed attention needs to be given to perceptions of health risks of smoking,
      especially among pregnant women.

PMID- 18058421
TI  - A case of rectal abuse of Preparation H.

PMID- 18058422
TI  - Neuropsychiatric insights in clinical practice: from relapse prevention toward
      relapse management.

PMID- 18058423
TI  - Do current government policies sufficiently regulate the interaction between
      viewing smoking in movies and adolescent smoking behavior?

PMID- 18058424
TI  - Intravenous zolpidem abuse: a case for serotonin depletion.

PMID- 18058429
TI  - Story stem narratives with young children: moving to clinical research and
      practice.
AB  - Story stem narrative methods have demonstrated reliability and validity as
      assessments of the young child's representations of parent - child and peer
      relationships. Most, but not all, prior research has been conducted with samples
      of typically developing children. Growing interest in the method from clinical
      researchers and child psychiatry clinics brings forward a number of critical
      issues in its use with children referred for severe behavioural disruption and
      mood disorder. This special issue of Attachment & Human Development provides a
      collection of papers that demonstrates some of the unique theoretical
      contributions of the method for clinical research. Practical aspects of using
      story stem methods with the referred child are also considered.

PMID- 18058430
TI  - Disorganized attachment representation and atypical parenting in young school age
      children with externalizing disorder.
AB  - We investigated the relationship of child attachment representation,
      psychopathology, and maternal atypical parenting in a high risk sample. Sixty-one
      consecutive clinical referrals with externalizing disorder aged 4 - 9 years were
      assessed for attachment representations measured with Manchester Child Attachment
      Story Task (MCAST), atypical parental expressed emotion (EE), maternal mood, and
      parent and teacher ratings of child behaviour. Disorganized attachment
      representations were found in 58% of cases, independent of ADHD symptoms.
      Pervasive disorganization was associated with very high maternal EE. Attachment
      status, maternal depression, and ADHD diagnosis were independently associated
      with parent-rated child behaviour problems; teacher ratings were associated with
      child's age and ADHD status. Disorganized attachment shows a high prevalence and
      independent associations with attention deficit symptomatology and maternal EE.

PMID- 18058431
TI  - Aggression and intentionality in narrative responses to conflict and distress
      story stems: an investigation of boys with disruptive behaviour problems.
AB  - In this study we examined whether antisocial boys show evidence of a reduced
      interpersonal interpretation of events (intentionality) specifically in story
      stem responses to social challenges that provoke fear and distress responses. Two
      conflict and two distress stems were administered to 5 - 8 year old boys, 41
      referred for disruptive behaviour problems and 25 non-referred boys. Raters blind
      to group membership scored dysregulated aggression and intentionality from
      transcripts of story responses. Referred boys had elevated aggression and lower
      intentionality scores across all stems compared to non-referred. However, there
      was a story type by group interaction; referred boys had substantially lowered
      intentionality in response to the distress stems, but not the conflict stems.
      Avoidant strategies that reduce threat related anxiety or fear also contribute to
      disruptive behaviour problems.

PMID- 18058432
TI  - Depressed and healthy preschoolers' internal representations of their mothers'
      caregiving: associations with observed caregiving behaviors one year later.
AB  - This study examined diagnostic group differences in children's internal
      representations of their mothers and mothers' parenting strategies 1 year later.
      Mother - preschool child dyads (N = 279) were examined. The sample included 151
      healthy, 75 depressed, and 53 disruptive disordered preschoolers. The MacArthur
      Story Stem Battery (MSSB) was administered at baseline. One year later, mothers'
      caregiving strategies were measured. Results indicated that higher depression
      severity was associated with preschoolers' greater use of negative and
      disciplinarian maternal representations. More positive maternal representations
      had supportive mothers who often expressed positive affect 1 year later.
      Preschoolers' negative and disciplinarian representations were associated with
      mothers' later nonsupportive behaviors and negative affect. Results suggest that
      the MSSB may be a useful child-informant method for interpreting depressed
      children's internalization of caregiving relationships.

PMID- 18058433
TI  - Story stem responses of preschoolers with mood disturbances.
AB  - Observing the young child's affect regulation and thought processes during a
      clinic assessment visit is of critical importance although challenging for
      children referred for mood disturbance. In this study, parents reported symptoms
      using standardized clinical interviews and story stems narratives were
      administered to 20 referred and 12 typically developing preschool age children.
      Comparison of the referred and typically developing children in our sample showed
      that specific story contexts varied in eliciting responses reflecting
      disorganization and thought disturbance from the referred children. The
      experience of using story stem narratives in the clinical assessment process
      suggests it provides a valuable complement to parent report for children referred
      for mood disturbance and mania symptoms but additional development and study of
      the method is necessary.

PMID- 18058434
TI  - Story stem narratives of clinical and normal kindergarten children: are content
      and performance associated with children's social competence?
AB  - This study examined whether content and performance in story stem narratives were
      associated with children's social competence, and whether children's symptom
      levels moderated these associations. Five-year-old children from a clinically
      enriched Swiss sample completed eight stories (N = 187). Teachers rated
      children's social competence. Parents and teachers rated behavioral/emotional
      symptoms that were used to categorize children into clinical (n = 80), borderline
      (n = 31), and normal (n = 74). Controlling for gender and verbal competence, no
      differences were found in story responses between normal and clinical children.
      However, pro-social/moral and disciplinary themes, and coherence and quality of
      narration were significantly associated with children's social competence. The
      associations between narratives and social competence were prominent in the
      clinical children, suggesting that narrative assessments may help to identify
      resources on which psychotherapeutic approaches can build.

PMID- 18058435
TI  - Future directions for doll play narrative research: a commentary.
AB  - Past research into doll play narratives has been productive in elucidating
      children's inner experiences, their determinants, and their role in child
      behaviour problems. The current volume takes this work forward in several
      directions: first, it indicates the value of designing story stems and coding
      schemes to address more specific questions about the developmental process of
      specific syndromes. Second, contributions demonstrate the "added value" provided
      by children's narratives, over and above information derived from other sources.
      Third, this recent research enhances our understanding of the role of parental
      representations and states of mind in influencing children's narratives; how
      these may come to influence child functioning via co-constructed parent - child
      dialogues is an important area for future research. Finally, possibilities of
      extending the clinical utility of doll play narratives are explored.

PMID- 18058436
TI  - Engaging imagination and the future: frontiers for clinical work.
AB  - Narrative theory indicates that assessment using narratives is expectant,
      collaborative, and has the potential to begin a process of change. A shift from
      thinking exclusively about meaning (subjectivity in the child) to thinking also
      about shared meaning (intersubjectivity between child and clinician-examiner)
      seems appropriate in the clinical context. Recent knowledge from the cognitive
      neurosciences makes a shift of this sort compelling and has further implications.
      More story stem narrative research at the level of assessing individual children
      needs to be done so there can be explicit links to treatment.

PMID- 18058437
TI  - Women's mental health.

PMID- 18058438
TI  - Women and depression: a 30 year learning curve.
AB  - This paper reviews 30 years of longitudinal research, initially undertaken to
      examine gender differences in rates of major depression and psychosocial risk
      factors for depression. The research focus has broadened to include the impact of
      anxiety on depression onset, coping styles for stress and depression, genetic and
      environmental influences on depression onset, and more recently, a shift towards
      examining positive mental health. The original cohort consisted of a socially
      homogenous group of postgraduate teacher trainees and does not attempt to
      represent the normal variability in an adult population. However, the issues
      raised by this research provide many insights about real and artefactual factors
      that contribute to the rate and experience of depression. The study findings are
      supplemented by data from other studies undertaken by this research team that are
      pertinent to the topic and add weight to some of the observations from the
      Teachers' Study.

PMID- 18058439
TI  - Women, catastrophe and mental health.
AB  - This paper examines the concept of catastrophic experience, its relationship to
      the range of acute and prolonged stressors to which women may be exposed and the
      broad impacts on their mental health and well-being. It identifies catastrophe in
      terms of multiple accumulated stresses including death, loss, victimization,
      demoralization, shame, stigmatization, helplessness and identity. Catastrophic
      experiences include personal violence in domestic circumstances of intimate
      partner abuse, sexual assault and child physical and sexual abuse. Women's
      experiences of loss through the violent deaths of children and loved ones may
      also have such enduring impacts. Terrorism victimizes men and women in this way,
      with the enduring impacts for women in terms of threat of ongoing attacks as well
      as acute effects and their aftermath. The catastrophes of war, conflict,
      genocide, sexual exploitation and refugee status differentially affect large
      numbers of women, directly and through their concerns for the care of their
      children and loved ones. Ultimate catastrophes such as Hiroshima and the
      Holocaust are discussed but with recognition of the very large numbers of women
      currently experiencing catastrophe in ongoing ways that may be silent and
      unrecognized. This is significant for clinical care and population impacts, and
      in the losses for women across such contexts.

PMID- 18058440
TI  - How does being female assist help-seeking for mental health problems?
AB  - OBJECTIVE: In Australia the prevalence of mental health problems does not vary by
      gender, but help-seeking and service utilization do. The aim of the present study
      was to examine a number of attitudinal factors that may influence help-seeking
      for mental health problems. METHOD: A cross-sectional community survey was
      conducted with a sample of 579 rural residents (57.9% female), who completed self
      report measures assessing stoicism, alexithymia, perceived and personal stigma
      and the various facets of the personality trait of openness to experience.
      RESULTS: Men scored higher on measures of stoicism and personal stigma associated
      with mental health problems than women, and compared to women had lower scores on
      the facets of openness to experience. CONCLUSIONS: Higher rates of help-seeking
      for mental health problems by women may be due to lower levels of stoicism and
      personal stigma related to mental health problems in women compared to men.

PMID- 18058441
TI  - Abortion and the struggle to be good in the 1970s.
AB  - OBJECTIVE: This study used social science methodology to illuminate an important
      clinical question that had been inaccessible to researchers until the 1970s. The
      question was what effect did an abortion have on normally rule abiding women.
      Abortion had been presumed to be illegal until a judicial decision in 1969. In
      1972 Australia's first abortion clinic was established, and the participants in
      this study were the women who attended it in 1974. This study was the first of
      its kind in Australia. METHOD: Interviews were conducted with 32 women who had a
      lawful termination of pregnancy and who agreed to be interviewed one year later.
      84% of women agreed to follow-up contact, and 34 were contacted. Social science
      theory about deviance, social stigma and norm violation was used to inform the
      study. RESULTS: Single, nulliparous women, were troubled by the potential
      exposure of their rule breaking sexual activity. The abortion was in part an
      action taken to preserve their persona as competent, moral beings capable of
      taking care of themselves. The abortion was the sensible next step in managing a
      missed menstrual period, the back up when contraception or plans for love and
      marriage failed. These women took mothering seriously and had an abortion to
      avoid becoming inadequate mothers. Abortion was a challenge to the married
      women's sense of themselves as good mothers, and their motives related to good
      mothering. The working class women had histories of managing tough and
      challenging life events, and they used the strengths, skills and networks they
      had established and applied those to the abortion decision. CONCLUSION: The most
      important and frequent effect of abortion was to make women feel more competent
      in managing their lives. The skills required to locate and access an abortion
      clinic against a backdrop of general social disapproval, expanded their sense of
      themselves as actors in their own lives. Their stories, as well as networks of
      support, enabled them to integrate abortion into their sense of themselves as
      good women.

PMID- 18058442
TI  - Preliminary findings from the National Register of Antipsychotic Medication in
      Pregnancy.
AB  - OBJECTIVE: Following the presentation of a case study and an overview of current
      data highlighting the need for further research into the use of antipsychotic
      medication during pregnancy, the aim of the present paper was to outline the
      establishment of, and present preliminary data from, the National Register of
      Antipsychotic Medication in Pregnancy (NRAMP). METHOD: Australian women with a
      history of psychosis, including schizophrenia, bipolar affective disorder with
      psychosis, schizoaffective disorder and first-episode psychosis, who are
      pregnant, are currently being invited to participate. The confluence of
      speculated national pregnancy rates and epidemiological data regarding child
      bearing-age women with psychosis suggested an enrollment target of 100 women over
      a 24 month period. Details of antipsychotic medication are recorded throughout
      the pregnancy and for 1 year postnatally. Interviews with the mother are
      conducted 6 weekly antenatally, and then at 6 and 12 weeks, and 6 and 12 months
      postnatally, to assess symptoms of psychosis and depression, and attitudes
      towards parenting. In addition, consultations are conducted with the women's
      health-care providers to collate information regarding pharmacology and related
      side-effects, obstetric outcomes, psychiatric diagnoses and symptoms during
      pregnancy and for 1 year after delivery, and the provision of details on the
      baby's health and well-being. RESULTS: NRAMP was launched in 2005. Ethics
      approvals have been gained at 14 sites nationally. Thirty women have consented,
      and 11 have completed. Data including demographics, health-care provision and
      medication for the first 30 participants are presented. CONCLUSIONS: The
      establishment of NRAMP is an important strategy in improving the management of
      serious mental illness such as schizophrenia and related disorders, in women who
      are pregnant. This project involves extensive collaboration between many
      different clinical groups and industry, and shall culminate in an important
      resource to improve the quality of life for both patients and future generations.

PMID- 18058443
TI  - Antenatal psychosocial risk factors and depression among women living in
      socioeconomically disadvantaged suburbs in Adelaide, South Australia.
AB  - OBJECTIVE: This study reports the prevalence of psychosocial risk factors and the
      incidence of depression in women presenting for their first antenatal visit at a
      general hospital in a socioeconomically deprived area. We also investigated the
      association between specific psychosocial risk factors and antenatal depression.
      METHOD: Four hundred and twenty one women completed the Antenatal Psychosocial
      Questionnaire (APQ) and the Edinburgh Postnatal Depression Scale (EPDS). Logistic
      regression analysis was used to identify psychosocial risk factors predictive of
      EPDS caseness. RESULTS: 88% of women endorsed at least one psychosocial risk
      factor. 35.6% had been abused as children, 34.9% had suffered recent major life
      stresses, 24.5% had thoughts of self harm, 8% admitted to recently hitting or
      hurting someone in anger and 5.6% had been victims of violence since becoming
      pregnant. The incidence of depression, measured using an EPDS cut-off score of 10
      or more, was 29.7%. The questionnaires were generally acceptable, apart from
      questions about drug and alcohol abuse which were not completed by one in five
      subjects. Factors associated with an increased risk of antenatal depression were
      being hit by someone since becoming pregnant, having recently hit someone else in
      anger, obsessional traits, previous feelings of depression and anxiety, and
      requiring both past and current treatment for emotional problems. Protective
      factors were having someone to talk to and feeling confident. CONCLUSION: Our
      findings suggest that women birthing at the LMHS are a very vulnerable group.
      Violence (either by or towards the pregnant women) was the strongest predictor of
      antenatal depression and may be under recognized. Antenatal screening for
      psychosocial risk factors and depression was useful and was well accepted by the
      women and the clinic staff. It is important that appropriate services are
      available once women at risk are identified.

PMID- 18058444
TI  - Does antenatal screening for psychosocial risk factors predict postnatal
      depression? A follow-up study of 154 women in Adelaide, South Australia.
AB  - OBJECTIVE: This study investigated the effectiveness of antenatal screening for
      psychosocial risk factors in predicting postnatal depression, in women living in
      a socioeconomically deprived area. METHOD: 154 women completed the Antenatal
      Psychosocial Questionnaire (APQ) and the Edinburgh Postnatal Depression Scale
      (EPDS). Logistic regression analysis was used to identify antenatal psychosocial
      risk factors predictive of EPDS caseness, with an EPDS score of 10 or more being
      taken to indicate depression. RESULTS: Antenatal depression was more common than
      postnatal depression. 44 women (30%) met criteria for antenatal depression and 33
      women (22.6%) met criteria for postnatal depression. 21 women (14.4%) were
      depressed both before and after delivery of their baby, and women who had
      antenatal depression were significantly more likely to be depressed postnatally.
      Whilst there were high rates of endorsement of antenatal psychosocial risk
      factors, the only item from the APQ that predicted postnatal depression was
      emotional abuse as a child. CONCLUSION: Antenatal screening for psychosocial risk
      factors was useful in identifying problems during the antenatal period, but was
      not useful as a predictor of postnatal depression.

PMID- 18058445
TI  - Single motherhood versus poor partner relationship: outcomes for antenatal mental
      health.
AB  - OBJECTIVE: In the transition to parenthood, lack of social support significantly
      impacts on maternal mood. This paper compares the influence of single-mother
      status and level of partner support in a partnered relationship, on antenatal
      emotional health. METHODS: Antenatal demographic, psychosocial and mental health
      data, as determined by Edinburgh Postnatal Depression Scale (EPDS) score, were
      collected from 1578 women. The association between these variables, and marital
      status, was investigated using logistic regression. RESULTS: Sixty-two women
      (3.9%) were identified as single/unpartnered. Elevated EPDS scores (>12) were
      found in 15.2% (240/1578) of the total cohort and 25.8% (16/62) of the
      single/unpartnered women. EPDS scores were significantly lower for
      single/unpartnered women than for women with unsupportive partners (8.9+/-5.3 vs
      11.9+/-6.5, p<0.001). Compared to the partnered cohort, single/unpartnered women
      were more likely to have experienced >or=2 weeks of depression before the current
      pregnancy (p<0.05), a previous psychopathology (p<0.001), emotional problems
      during the current pregnancy (p<0.01) and major life events in the last year
      (p<0.01). Binary logistic regression modelling to predict antenatal EPDS scores
      suggests that this is mediated by previous psychiatric history (p<0.001) and
      emotional problems during pregnancy (p=0.02). CONCLUSION: Women in a partnered
      relationship with poor partner-derived support were at an increased risk of
      elevated antenatal EPDS scores compared to single/unpartnered women. A previous
      history of depression and current emotional problems, rather than single mother
      status, were significant risk factors for elevated EPDS scores. The present study
      reiterates the contribution of psychosocial risk factors as important mediators
      of antenatal emotional health.

PMID- 18058446
TI  - Postnatal mental health of women giving birth in Australia 2002-2004: findings
      from the beyondblue National Postnatal Depression Program.
AB  - OBJECTIVES: To describe the postnatal mental health status of women giving birth
      in Australia 2002-2004 at 6-8 weeks postpartum. METHOD: Women were recruited from
      43 health services across Australia. Women completed a demographic questionnaire
      and an Edinburgh Postnatal Depression Scale (EPDS) in pregnancy; the latter was
      repeated at 6-8 weeks following childbirth. RESULTS: A total of 12 361 postnatal
      women (53.8% of all postnatal women surveyed) completed questionnaires as part of
      a depression screening programme; 15.5% of women screened had a postnatal EPDS>9
      and 7.5% of women had an EPDS>12 at 6-8 weeks following childbirth. There was
      significant variation between States in the percentage of women scoring as being
      potentially depressed. The highest percentage of women scoring EPDS>12 were in
      Queensland and South Australia (both 10.2%) while Western Australia had the
      lowest point prevalence (5.6%). Women recruited from private health services in
      Western Australia had a significantly lower prevalence of elevated EPDS scores
      than those women recruited from the public health service (EPDS >12: 3.6% vs
      6.4%, p=0.026); differences in the prevalence of elevated EPDS scores were not
      significant between public and private in Australian Capital Territory (EPDS>12:
      7.6% vs 5.8%, p=0.48), where income and education was significantly higher than
      other States for both groups. CONCLUSIONS: Postnatal depressive symptoms affect a
      significant number of women giving birth in Australia, and the point prevalence
      on the EPDS may be higher for women in the public sector, associated with lower
      incomes and educational levels. Maternity services--particularly those serving
      women with these risk factors--need to consider how they identify and manage the
      emotional health needs of women in their care. Specific State-related issues,
      such as availability of specialist perinatal mental health services and liaison
      between treating health professionals, also need to be considered.

PMID- 18058447
TI  - Do women express and experience psychosis differently from men? Epidemiological
      evidence from the Australian National Study of Low Prevalence (Psychotic)
      Disorders.
AB  - OBJECTIVE: To examine how women differ from men in their expression and
      experience of psychosis. METHOD: Using an epidemiological sampling frame, 1090
      cases of psychosis (schizophrenia, schizoaffective disorder, affective psychoses,
      and other psychoses) were randomly selected from a catchment of 1.1 million
      people as part of the Australian Study of Low Prevalence (Psychotic) Disorders.
      Women and men were compared with respect to their premorbid functioning, onset
      and course of illness, symptomatology, levels of disability and service
      utilization. RESULTS: Results within diagnostic groupings confirm differences in
      how men and women experience and express their illness. Within each diagnostic
      group, women reported better premorbid functioning, a more benign illness course,
      lower levels of disability and better integration into the community than men.
      They were also less likely to have a chronic course of illness. There were no
      significant differences in age at onset. Differences between women across the
      diagnostic groups were more pronounced than differences between women and men
      within a diagnostic group. In particular, women with schizophrenia were severely
      disabled compared to other women. CONCLUSIONS: These comparisons across
      diagnostic groupings are among the most systematic and comprehensive in the
      literature. It is likely that several mechanisms are needed to explain the
      differences. Greater social integration and functioning in women across
      diagnostic groups may well reflect culturally and socially determined gender
      differences. In contrast, variability and attenuated findings with respect to
      symptom profiles beg the question of biological mechanisms with some degree of
      specificity.

PMID- 18058448
TI  - Hormone modulation: a novel therapeutic approach for women with severe mental
      illness.
AB  - OBJECTIVES: Accumulating evidence describes the effects of oestrogen and other
      gonadal hormones on the central nervous system and, in particular, on the mental
      state of women. Evidence supporting the psychotherapeutic effects of exogenous
      oestrogen has started to emerge only over the past two decades. The purpose of
      the present paper was to provide an overview of different applications of
      adjunctive hormones, as treatments for symptoms of severe mental illness in
      women. METHODS: Three case reports are presented: in each case the woman selected
      had participated in large, double-blind, randomized controlled trials exploring
      hormone modulation. Case study 1 presents a premenopausal woman with
      schizophrenia, who received an 8 week trial of daily adjunctive 200 microg
      transdermal oestradiol. Case study 2 presents a postmenopausal woman with
      schizophrenia on a 12 week trial of adjunctive raloxifene hydrochloride 120 mg
      per day. Case study 3 presents a woman with schizoaffective disorder, in the
      manic phase, who received tamoxifen 40 mg per day for 28 days. RESULTS:
      Adjunctive oestradiol was associated with an improvement in symptoms of psychosis
      in a premenopausal woman with schizophrenia; adjunctive raloxifene was associated
      with an improvement in cognitive functioning in a postmenopausal woman with
      schizophrenia; and adjunctive tamoxifen was associated with an improvement in
      symptoms of mania in a woman with schizoaffective disorder. CONCLUSIONS: These
      findings are consistent with preliminary research trials suggesting that
      adjunctive hormone modulation is a promising area of gender-specific treatment
      for serious mental illness.

PMID- 18058449
TI  - Simpler explanation for catatonia.

PMID- 18058451
TI  - Effects of commercial enzymes on the adhesion of a marine biofilm-forming
      bacterium.
AB  - The antifouling potential of commercial hydrolases, four proteases, seven
      glycosidases and one lipase was evaluated on the adhesion of marine
      Pseudoalteromonas sp. D41. The experimental method, adapted to screen antifouling
      agents, was based on bacterial adhesion in natural sterile sea water in a
      microtiter plate and on total biomass quantification by the fluorescent dye DAPI
      (4[prime]6-diamidino-2-phenylindole). Savinase (subtilisin) was the most
      effective hydrolase in both the prevention of bacterial adhesion and the removal
      of adhered bacteria. However, some enzymatic preparations tested such as Amano
      protease were not only ineffective but also increased the number of adhered
      bacterial cells. Enumeration using epifluorescence microscopy of CTC (5-cyano-2,3
      ditolyl tetrazolium chloride) and DAPI stained adhered D41 cells confirmed these
      observations. Overall, these results demonstrated that hydrolases could either
      prevent adhesion and remove adhered bacterial cells effectively, or conversely
      increase bacterial adhesion, depending on enzymatic concentrations and the type
      of enzymes tested.

PMID- 18058452
TI  - Sodium dodecyl sulfate allows the persistence and recovery of biofilms of
      Pseudomonas fluorescens formed under different hydrodynamic conditions.
AB  - The effect of the anionic surfactant sodium dodecyl sulfate (SDS) on Pseudomonas
      fluorescens biofilms was investigated using flow cell reactors with stainless
      steel substrata, under turbulent (Re = 5200) and laminar (Re = 2000) flow. Steady
      state biofilms were exposed to SDS in single doses (0.5, 1, 3 and 7 mM) and
      biofilm respiratory activity and mass measured at 0, 3, 7 and 12 h after the SDS
      application. The effect of SDS on biofilm mechanical stability was assessed using
      a rotating bioreactor. Whilst high concentrations (7 mM) of SDS promoted
      significant biofilm inactivation, it did not significantly reduce biofouling.
      Turbulent and laminar flow-generated biofilms had comparable susceptibility to
      SDS application. Following SDS exposure, biofilms rapidly recovered over the
      following 12 h, achieving higher respiratory activity values than before
      treatment. This phenomenon of post-treatment recovery was more pronounced for
      turbulent flow-generated biofilms, with an increase in SDS concentration. The
      mechanical stability of the biofilms increased with surfactant application,
      except for SDS concentrations near the critical micellar concentration, as
      measured by biofilm removal due to an increase in external shear stress forces.
      The data suggest that although SDS exerts antimicrobial action against P.
      fluorescens biofilms, even if only partial and reversible, it had only limited
      antifouling efficacy, increasing biofilm mechanical stability at low
      concentrations and allowing significant and rapid recovery of turbulent flow
      generated biofilms.

PMID- 18058453
TI  - Ambulatory blood pressure adds to explaining benefits of AT-1 receptor blockade
      in the treatment of left ventricular hypertrophy.

PMID- 18058454
TI  - Undiagnosed obesity in hypertension: clinical and therapeutic implications.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of obesity in
      patients with hypertension and to evaluate the relationship between obesity,
      metabolic syndrome (MetS) and blood pressure (BP) control. MATERIALS AND METHODS:
      We conducted an epidemiological survey in a sample of 19,039 patients with
      hypertension who consecutively attended a primary healthcare center. Patients
      were considered to have hypertension if the BP was > or =140/90 mmHg or > or
      =130/80 mmHg in diabetic patients or if they were undergoing pharmacological
      treatment for hypertension. The obesity was based on body mass index (BMI).
      Overweight was if the BMI was > or =25 kg/m2, obese > or =30 kg/m2 and severe
      obesity (SO) if BMI was > or =40 kg/m2. Abdominal obesity (AO) was considered
      when the waist circumference was greater than 102 cm in men and 88 cm in women.
      RESULTS: The prevalence of obesity in our hypertensive patients was 51.6% and
      among these 3.8% had SO. Furthermore, 38.7% were overweight. AO was observed in
      66.1% of the whole. Both obesity and AO were significantly more prevalent in
      women. When evaluating the patients according to categories of BMI, we observed
      greater levels of BP (from 145.5/84.5 to 149.5/89 mmHg, p<0.0001), worse control
      over BP (from 29.6% to 15.4%, p<0.0001) and a greater prevalence of MetS (from
      20.8% to 66.9%, p<0.0001) as weight increased. Likewise, an increase in both BMI
      and AO was associated with worse control of BP (obesity, OR = 1.343 (95%
      confidence interval, CI, 1.251-1.442); AO, OR = 1.292 (95% CI 1.201-1.389).
      CONCLUSIONS: There is a high prevalence in Spain of obesity and AO in patients
      with hypertension. These conditions are associated with metabolic alterations and
      worse BP control.

PMID- 18058455
TI  - Arterial stiffness is related to augmented seasonal variation of blood pressure
      in hypertensive patients.
AB  - BACKGROUND: Seasonal variation in blood pressure (BP), a usual tendency of both
      systolic (SBP) and diastolic BP (DBP) to rise during winter in hypertensive
      patients, may be related to the higher cardiovascular mortality in winter.
      However, it is not yet clear what factors are relevant to the seasonal BP
      changes. We hypothesized that arterial stiffness is related to the BP changes
      between summer and winter. METHODS AND RESULTS: Eighty-five elderly (>55 years)
      patients with essential hypertension (33 males, 64+/-6.0 years) were enrolled.
      Seasonal BP profiles over at least 2 years were studied along with arterial
      stiffness and clinical variables (age, gender, smoking, duration of hypertension,
      anti-hypertensive medications and body mass index). Both SBP and DBP were
      significantly higher during winter compared with three other seasons (spring
      128+/-10.0/79+/-7.3 mmHg, summer 127+/-9.8/78+/-7.1 mmHg, autumn 127+/-10.3/78+/
      8.0 mmHg, winter 136+/-12.5/81+/-7.6 mmHg; SBP changes; p<0.001, DBP changes;
      p<0.001). There were no significant seasonal differences among spring, summer and
      autumn. Pulse wave velocity (PWV), a widely used clinical indicator of arterial
      stiffness was correlated with winter-summer differences in SBP (r = 0.272, p =
      0.012), but not in DBP (r = 0.188, p = 0.085). Age, which was correlated with PWV
      strongly (p<0.001), was not significantly related to the seasonal changes in BP
      (SBP changes; p = 0.114, DBP changes; p = 0.298). No other clinical variables had
      significant correlation with seasonal BP changes. Multivariate regression
      analysis revealed that PWV is the only significant predictor for winter-summer
      SBP changes. CONCLUSIONS: Our results established a feasible link between
      arterial stiffness and seasonal BP variation. These findings may partly explain
      higher cardiovascular risk in patients with increased arterial stiffness.

PMID- 18058456
TI  - Safety and efficacy of the oral direct renin inhibitor aliskiren in elderly
      patients with hypertension.
AB  - OBJECTIVES: To evaluate the efficacy, safety and tolerability of aliskiren in
      elderly patients (> or =65 years old) with essential hypertension. METHODS: In
      this double-blind, multicenter study, 355 elderly patients with hypertension
      [office mean sitting systolic blood pressure (msSBP) > or =145-<180 mmHg and mean
      24-h ambulatory systolic BP (ASBP) > or =135 mmHg] were randomized to once-daily
      treatment for 8 weeks with aliskiren 75 mg (n = 91), 150 mg (n = 84), 300 mg (n =
      94) or the comparator lisinopril 10 mg (n = 86). The primary efficacy variable
      was change in mean 24-h ASBP. RESULTS: At endpoint, aliskiren 75 mg, 150 mg, 300
      mg and lisinopril 10 mg lowered mean 24-h ASBP (least-squares mean+/-SEM) by
      8.4+/-0.8, 7.1+/-0.8, 8.7+/-0.8 and 10.2+/-0.9 mmHg, and mean 24-h ambulatory
      diastolic BP by 4.5+/-0.5, 3.6+/-0.5, 3.9+/-0.5 and 6.3+/-0.5 mmHg, respectively,
      with no significant difference between aliskiren doses. The trough-to-peak ratio
      for ASBP reduction with aliskiren 75 mg, 150 mg, 300 mg and lisinopril 10 mg was
      0.77, 0.64, 0.79 and 0.87, respectively. All treatments lowered office msSBP and
      mean sitting diastolic BP (msDBP) compared with baseline. A significantly greater
      proportion of patients receiving aliskiren 300 mg achieved BP control
      (msSBP/msDBP <140/90 mmHg) compared with those receiving aliskiren 75 mg (36.2%
      vs 24.2%, p = 0.033). There was no evidence of dose-related increases in the rate
      of adverse events with aliskiren treatment. CONCLUSIONS: Aliskiren, a novel
      direct renin inhibitor, provides effective 24-h BP lowering with no evidence of
      dose-related increases in the incidence of adverse events in elderly patients
      with hypertension.

PMID- 18058457
TI  - Losartan versus atenolol on 24-hour ambulatory blood pressure. A LIFE substudy.
AB  - OBJECTIVE: The Losartan Intervention For Endpoint reduction in hypertension
      (LIFE) study showed that losartan-based treatment reduced risk of the composite
      endpoint of cardiovascular death, stroke and myocardial infarction compared with
      atenolol-based treatment in patients with hypertension and left ventricular
      hypertrophy with similar office blood pressure (BP) reduction. Our aim was to
      investigate the effect of losartan- and atenolol-based treatment on 24-h
      ambulatory BP and heart rate (HR) in LIFE. METHODS: In 110 patients, 24-h
      ambulatory BP and heart rate were recorded at baseline and 1 year after
      randomization. RESULTS: Ambulatory BP was comparably reduced throughout the 24-h
      period after 1 year of losartan- vs atenolol-based antihypertensive treatment.
      Office and ambulatory BP were comparably reduced in the follow-up period. Early
      morning surge in BP was similar between groups. Non-dipping status was more
      frequent in the losartan group (p = 0.01). From baseline to Year 1 the 24-h HR
      profile for the losartan group was unchanged, but, as expected, there was a
      significant decrease in daytime HR in the atenolol group, which was not as large
      during early night-time. CONCLUSION: There were no differences in 24-h BP burden
      and HR that could explain the difference in outcome in favor of losartan vs
      atenolol in the LIFE study.

PMID- 18058459
TI  - Epigenetic regulation as a new target for breast cancer therapy.

PMID- 18058460
TI  - "Of models and men (or women)"--a brief story of a mathematical model and its
      influence on the management of ovarian cancer.

PMID- 18058461
TI  - Telomere length in hepatocellular carcinoma and paired adjacent non-tumor tissues
      by quantitative PCR.
AB  - Telomere shortening limits the proliferative capacity of human cells, restrains
      the regenerative capacity of organ systems during chronic diseases and aging and
      also induces chromosomal instability as well as initiation of cancer. Previous
      studies demonstrated that telomeres are often significantly shorter in tumor
      tissue, including hepatocellular carcinoma (HCC), compared to the surrounding
      tissue, but telomere length in HCC tissues was not correlated with several
      clinical parameters, such as age, sex, HBV or HCV infections and tumor size. In
      the present study, the telomere length ratio of 36 paired HCC, and their adjacent
      non-tumor tissues was measured by quantitative PCR (Q-PCR). The mean telomere
      lengths (SD) for HCC and adjacent non-tumor tissues were 0.26 (0.10) and 0.47
      (0.20) respectively (t = 6.22, P < 0.0001). There was a large difference in the
      distribution of subjects based on telomere length in tumor and adjacent non-tumor
      tissues. The number of tumors with telomere length shorter than 0.50 was much
      higher than that of adjacent non-tumor tissues; more than 90% of the tissues with
      telomere length > or = 0.50 were adjacent non-tumor tissues. The correlations
      between telomere length and aflatoxin B1- and polycyclic aromatic hydrocarbon-DNA
      adducts level, p53 mutations and p16 hypermethylation status were also tested,
      but no significant associations were found. The relationship between telomere
      length shortening, chemical carcinogen exposure, and genetic and epigenetic
      changes in hepatocarcinogenesis needs further investigation.

PMID- 18058462
TI  - Downregulation of survivin is associated with reductions in TNF receptors' mRNA
      and protein and alterations in nuclear factor kappa B signaling in urothelial
      cancer cells.
AB  - Because survivin is selectively expressed in and associated with an unfavorable
      prognosis in transitional cell carcinoma of the bladder (TCC), we treated T-24
      cells with survivin siRNA. Survivin siRNA treatment caused a profound decrease of
      survivin protein that was associated with decreased cell growth, a specific G2/M
      arrest and increased cytochrome c release. Microarray analysis of apoptosis genes
      showed that levels of 14/114 gene products were decreased after 72 hours
      treatment with survivin siRNA, including survivin, three TNF receptors, Akt, c
      Abl, caspases and their related genes and Bcl-2 and NF-kappaB signaling related
      genes. TNFR1, pro-caspase-2 and Akt protein levels were decreased after survivin
      siRNA treatment for 48 and 72 hours. Downregulation of survivin causes changes in
      mitosis and apoptosis, which may be related to changes in TNF receptors and NF
      kappaB signaling.

PMID- 18058463
TI  - Promoter hypermethylation of the RUNX3 gene in esophageal squamous cell
      carcinoma.
AB  - Alteration in transforming growth factor-beta (TGF-beta) signaling pathway is one
      of the main causes of esophageal squamous cell carcinoma (ESCC). The human runt
      related transcription factor 3 (RUNX3), an important component of TGF-beta
      pathway which is located at 1p36, is commonly deleted in a variety of human
      cancers, including ESCC. Hypermethylation of RUNX3 promoter was frequently found
      in gastrointestinal cancers, including those of stomach, liver, colon and
      pancreas. However, RUNX3 promoter methylation status in ESCC has not been
      studied. The aim of this study was to determine whether promoter methylation of
      the RUNX3 gene correlates with ESCC tumor progression.Accordingly, we first
      determined RUNX3 mRNA expression and methylation status of its promoter region in
      42 primary tumors with ESCC and Eca-109, an ESCC cell line. Loss of RUNX3 mRNA
      expression was detected by RT-PCR in 23 out of 42 (54.8%) ESCC specimens and Eca
      109 cells. The Promoter hypermethylation was detected by Methylation Specific
      Polymerase Chain Reaction (MS-PCR) in 27 out of 42 (64.3%) ESCC specimen and Eca
      109 cells. Importantly, we found positive correlations, not only between the
      promoter hypermethylation and tumor clinical pathologic stages (P = 0.003), but
      also between the loss of RUNX3 mRNA expression and the tumor progression (P =
      0.016). Finally, we observed that the loss of RUNX3 mRNA expression is
      statistically correlated with the promoter hypermethylation in these tumors (P <
      0.001). Our results suggest that epigenetic silencing of RUNX3 gene expression by
      promoter hypermethylation may play an important role in ESCC development.

PMID- 18058464
TI  - Inhibition of telomerase activity in cancer cells using short hairpin RNA
      expression vectors.
AB  - Telomerase activity is mainly regulated by the human telomerase reverse
      transcriptase (hTERT) gene. Our objective was to investigate the effect of short
      hairpin RNA (shRNA) directed against hTERT mRNA on telomerase activity in
      laryngeal cancer cells (Hep-2), nasopharyngeal carcinoma cells (NEC), and human
      bone marrow mesenchyme stem cells (hMSCs). Short hairpin RNA expression vectors
      targeting the messenger RNA of hTERT were constructed. Cells were treated with
      shRNA expression vectors directed against hTERT mRNA and control vectors that
      included mismatched shRNA. We found that treatment of special shRNA expression
      vectors induced significantly decrease in hTERT expression, telomerase activity,
      and cell viability in Hep-2 and NEC cells. In contrast, the shRNA control showed
      none of these effects. And none of these effects appeared in hMSCs cells. Our
      results suggest that shRNA against hTERT mRNA inhibits telomerase activity and
      cell viability through suppression of the hTERT expression in cancer cells. And
      this treatment has no side effect on healthy cells lack of telomerase activity.
      RNA interfering technology may be a promising strategy for the treatment of
      cancers.

PMID- 18058465
TI  - DARPP-32 mediates multidrug resistance of gastric cancer through regulation of P
      gp and ZNRD1.
AB  - Here, we firstly investigated the roles of DARPP-32 in multidrug resistance of
      gastric cancer cells. Inhibition of DARPP-32 by small interfering RNA led to
      decreased sensitivity of cells to chemotherapeutic drugs, accompanied by
      increased capacity of cells to efflux adriamycin. Inhibition of DARPP-32
      expression could significantly up-regulate the expression of permeability
      glycoprotein (P-gp) and zinc ribbon domain-containing 1 (ZNRD1), but not alter
      the expression of multidrug resistance-associated protein or glutathione
      transferase. The DARPP-32 siRNA-mediated MDR could be reversed by inhibitor of P
      gp or siRNA of ZNRD1, indicating DARPP-32 might mediate MDR of gastric cancer
      through regulation of P-gp and ZNRD1.

PMID- 18058466
TI  - Diffusion tensor imaging and chemical shift imaging assessment of heterogeneity
      in low grade glioma under temozolomide chemotherapy.
AB  - Diffusion tensor imaging and multiple voxel magnetic resonance spectroscopy were
      performed in the MRI follow-up of a patient with a glioma treated with
      temozolomide chemotherapy. Tumor shrinkage was paralleled by reductions in
      choline level and by increases in apparent diffusion coefficient indicating
      decreased cellularity. Within the tumor, choline level and apparent diffusion
      coefficient showed a significant inverse correlation (P < 0.01). Fractional
      anisotropy distribution in the tumor correlated positively with N-acetyl
      aspartate level (P < 0.001), indicating that these parameters reflect (remaining)
      axonal structure. Tumor lactate level, also found to decrease under therapy, did
      not correlate with any other parameter.

PMID- 18058467
TI  - Adjuvant therapy with raltitrexed in patients with colorectal cancer intolerant
      of 5-fluorouracil: British Columbia Cancer Agency experience.
AB  - BACKGROUND: Severe 5-FU toxicity in adjuvant therapy of colorectal cancer may
      require change of therapy. We retrospectively explored the safety and efficacy of
      adjuvant raltitrexed in patients intolerant of 5-FU. METHODS: Over a 5 year
      period, patients who received 5-FU and subsequent raltitrexed therapy were
      identified. RESULTS: There were 44 patients, (39 stage III). Median number of
      prior 5-FU cycles was 2. Three year relapse free and overall survival proportions
      for stage III patients were 70.8% and 83.6%, respectively. CONCLUSIONS:
      Raltitrexed adjuvant therapy can be given safely and effectively in patients
      where further 5-FU is contraindicated.

PMID- 18058468
TI  - Macrophage migration inhibitory factor in cancer.
AB  - The objective of this study was to investigate the expression of macrophage
      migration inhibitory factor (MIF) in patients with colorectal cancer (GIS) and
      malignant melanoma (MM). The study group consists of pathologically verified
      colorectal cancer (n = 63) and malignant melanoma (n = 65) patients and healthy
      controls (n = 25). Serum MIF concentrations were determined by enzyme-linked
      immunosorbent assay. Serum values of the patients were significantly higher than
      the controls (p < 0.001 for GIS, p = 0.032 for MM). Diagnostic sensitivity and
      specificity were calculated for MIF for colorectal and malignant melanoma. The
      results demonstrate that colorectal cancer express and secrete large amounts of
      MIF.

PMID- 18058469
TI  - Receptor for advanced glycation end products (RAGE)--soluble form (sRAGE) and
      gene polymorphisms in patients with breast cancer.
AB  - Receptor for advanced glycation end products (RAGE) may be involved in the
      pathogenesis of the cancer progression and metastasis. Pathological effects
      mediated via RAGE are physiologically inhibited by soluble RAGE (sRAGE), so the
      higher sRAGE levels may confer the patients with cancer with better outcome. The
      aim was to study sRAGE and RAGE gene polymorphisms in patients with breast
      cancer. The authors studied sRAGE and RAGE polymorphisms in 120 patients with
      breast cancer (subdivided based on the clinical stage, histologic grading,
      expression of hormonal and Her2/neu receptors) and in 92 healthy controls.
      Despite higher serum concentrations of AGEs, serum concentrations of sRAGE were
      lower in patients with breast cancer compared to healthy controls (1581 +/- 777
      versus 1803 +/- 632 ng/mL, p < 0.05). Serum levels of sRAGE were higher in
      patients with advanced breast cancer (stage III), lower grade and positive
      estrogen receptors, and intermediate positivity of Her2/neu receptors and were
      also influenced genetically (Gly82Ser and 2184 AG polymorphisms of the RAGE
      gene). Decreased sRAGE levels in patients with breast cancer may contribute to
      the progression of the disease. Patients with better outcome (low grade and
      positive estrogen receptors) have higher sRAGE levels. Progression of the
      disease, may, however, increase sRAGE levels, possibly as a compensatory
      mechanism to counteract further progression.

PMID- 18058470
TI  - Transforming growth factor-beta 1 gene polymorphisms and expression in the blood
      of prostate cancer patients.
AB  - The transforming growth factor beta 1 (TGF-beta1) is a multifunctional cytokine
      with several regulatory activities in tumor cells affecting growth,
      differentiation, and function. Alterations in gene expression, secretion, and
      regulation of TGF-beta1 may lead to a favorable environment for tumor development
      by angiogenesis stimulation and immune system suppression. We evaluated the
      influence of the TGFB1 polymorphisms by ARMS-PCR, Leu10Pro, and Arg25Pro, on
      prostate cancer (PCa) and benign prostatic hyperplasia (BPH). We assessed TGFB1
      polymorphisms and their relation to mRNA levels (semi-quantitative RT-PCR) in
      blood samples as well as the implications in disease occurrence and progression.
      Peripheral blood samples from 175 patients were analyzed as to 92 BPH and 83 PCa.
      Samples obtained from 132 healthy males were used as negative controls. PCa
      patients with a Gleason score greater than 7 presented a higher frequency of the
      C allele (Leu10Pro). This allele was associated with a higher risk of developing
      PCa and BPH compared to the population (2.6 and 3.6 times higher, respectively).
      Patients with TGFB1 transcript levels equal to or more than 70% higher than
      control levels presented a 5.34 and 2.14-fold higher risk of having PCa and BPH,
      respectively, relative to the population. No association was detected between
      polymorphisms and mRNA levels. The C allele of the Leu10Pro polymorphism may
      predispose men to a more rapid cancer progression. Additionally, higher mRNA
      levels in the peripheral blood of PCa patients suggest that tumor cells may be
      disseminated in the circulation and could be used as a biomarker for extra
      capsular invasion.

PMID- 18058471
TI  - CYR61: a new measure of lung cancer outcome.
AB  - Cysteine-rich protein 61 (Cyr61) is a member of a family of growth factor
      inducible, immediate-early genes. In this report, the authors measured the
      expression of Cyr61 mRNA in 94 human lung tumors and their normal matched lung
      samples. The Cyr61 mRNA levels were quantified by real time reverse transcriptase
      polymerase chain reaction and calculated as a tumor/normal Cyr61 mRNA ratio in
      each case. Compared with normal matched lung tissues, expression of Cyr61 was
      decreased in 74 of 94 (79 percent) lung tumors. Differences in distribution of
      patient characteristics, such as gender, age, tumor size, and pathological
      diagnosis, between high or low Cyr61 expressing groups were not statistically
      significant. However, differences in distribution of clinical stage between high
      or low Cyr61 expressing groups was statistically significant; that is, the Cyr61
      low expressor group was clinically more advanced than the Cyr61 high expressor
      group (p = 0.046). Furthermore, Cyr61 levels of the patients with N0 and N1
      diseases were significantly higher than the expression in the N2 patients (p =
      0.047). The 3-year survival between the Cyr61 very low tumor expressor group
      compared to matched normal lung (39 patients) and the higher Cyr61 expressor
      group (52 patients) was statistically significant (59 versus 91 percent; p =
      0.05). Taken together, Cyr61 appears to guard against metastatic disease because
      low expression is associated with more advanced disease; and therefore,
      expression levels of Cyr61 correlate with the prognosis of lung cancer.

PMID- 18058472
TI  - The occurrence and the type of germline mutations in the RET gene in patients
      with medullary thyroid carcinoma and their unaffected kindred's from Central
      Poland.
AB  - We aimed to investigate the occurrence and types of pathogenic mutations in the
      RET gene in patients with MTC of the Central Poland population and in their
      relatives. DNA was extracted from the peripheral blood lymphocytes of a total of
      330 persons, including 235 MTC patients and 95 of their unaffected kindred's.
      Exons 10, 11, 13, 14, 15 and 16 of the RET gene were amplified by PCR and
      sequenced. Sixty-seven people were found to carry pathogenic, germline mutations
      in the RET gene. In exon 10, C609F, C609R and C609Y (3 families), C618G, C618F (2
      families), and C620G (4 families) mutations were identified. In exon 11, C634R (8
      families) and C649L mutations (1 patient) were found. Five families carried Y791F
      mutation in exon 13. One patient with PTC revealed the presence of a Y791F
      mutation. In 3 families, exon 14 of the RET gene harbored the following
      mutations: V804L (1 patient), E819K (1 patient) and R844Q (1 patient). In 1
      family, the S891A mutation was identified in exon 15, 3 families were found to
      carry mutations in exon16, R912P in 1 family and M918T in 2 families. In summary,
      of the 235 patients affected by MTC, 46 (19.6%) carried pathogenic RET gene
      mutations, 1 patient with RET mutation had kidney carcinoma, and 1 had PTC. The
      results show the occurrence of a variety of mutations prevalent in patients with
      MTC in the population of Central Poland. These results may contribute to a better
      diagnosis of medullary thyroid carcinoma.

PMID- 18058473
TI  - Interaction of cigarette smoking with cyclooxygenase-2 on ulcerative colitis
      associated neoplasia in mice.
AB  - The interactions of cigarette smoking with COX-2 on colitis and colitis
      associated adenoma formation were studied. Mice were induced with colitis and
      exposed to cigarette smoke (CS) and/or SC236 (a COX-2 inhibitor). Results
      indicated that CS did not alter acute colonic inflammation. Addition of SC236
      abolished the induction of proliferation and oxidative damage by colitis. Chronic
      SC236 treatment abolished the promoting effect of CS on colonic adenoma
      formation, via suppression of COX-2- and VEGF-mediated proliferation and
      angiogenesis, and reversed bcl-2-mediated inhibition of apoptosis by CS. To
      conclude, COX-2 inhibitor could be an implication on cancer prevention in smokers
      with chronic colitis.

PMID- 18058474
TI  - The role of bortezomib in the treatment of lymphoma.
AB  - Bortezomib is the first of the proteasome inhibitors to be used clinically. Among
      the various cancers susceptible to proteasome inhibition are the non-Hodgkin's
      lymphomas. Mantle cell lymphoma appears to be particularly sensitive, leading to
      the FDA approval of bortezomib in patients who have received at least one prior
      therapy. This demonstration of clinical efficacy has led to an explosion of
      research attempting to further understand the anti-tumor effect of proteasome
      inhibition and clinical investigations exploring bortezomib in combination with
      other agents. In this review, we will detail the clinical results and ongoing
      trials utilizing bortezomib in Hodgkin's and non-Hodgkin's lymphoma.

PMID- 18058475
TI  - Endothelin receptor antagonists in cancer therapy.
AB  - Endothelins are a family of peptide compounds which exert regulatory control over
      cellular processes important for growth, survival, invasion, and angiogenesis. In
      particular, endothelin-1, acting primarily through the endothelin-A receptor, is
      implicated in the neoplastic growth of multiple tumor types. In preclinical
      models, endothelin antagonism inhibits tumor cell proliferation, invasiveness,
      and new vessel formation, as well as attenuates osteoblastic and pain-related
      responses to tumor. Clinical testing of an orally bioavailable endothelin
      antagonist has demonstrated benefit in PSA progression, markers of bone turnover,
      and pain in men with prostate cancer, but has not demonstrated significant
      improvement in survival or time to cancer progression. Although this class of
      drugs is promising for targeted anti-cancer therapy, their role in treatment
      remains to be defined by completion of future clinical trials.

PMID- 18058476
TI  - Metabolic side effects and cardiovascular events of diuretics: should a diuretic
      remain the first choice therapy in hypertension treatment? The case of yes.
AB  - Essential hypertension is a major cause of cardiovascular morbidity and mortality
      in the Western world. Numerous clinical trials have demonstrated that the
      treatment of hypertension results in a substantial reduction of hypertension
      related morbidity and mortality. The efficacy and safety of diuretics has been
      shown in many clinical trials. Like most other antihypertensive agents, the side
      effects of diuretics are mostly benign and mild. The metabolic side effects of
      diuretics, however, have been a bone of contention for a long time. In this
      paper, we describe the most important and frequent metabolic side effects of
      diuretics, and emphasize particularly the non-life-threatening effect of
      diuretics on ventricular arrhythmias due to their hypokalemic effect, the
      detection of the new onset diabetes (perhaps caused by the administration of
      diuretics itself), and their significant beneficial effect on cardiovascular and
      cerebrovascular morbidity and mortality. At the end of the article, we
      highlighted the differences regarding the prescription of diuretics between the
      recently published American and European Guidelines of hypertension.

PMID- 18058477
TI  - Increase in nitric oxide and reductions in blood pressure, protein kinase C beta
      II and oxidative stress by L-carnitine: a study in the fructose-fed hypertensive
      rat.
AB  - Recently we showed that the administration of intraperitoneal L-carnitine (CA)
      has insulin-sensitizing effects in the high fructose-fed Wistar rat, a widely
      used model of metabolic syndrome. The present study was conducted to examine the
      regulatory effects of CA on blood pressure (BP) and related pressor mechanisms.
      Fructose-fed rats (FFR) showed elevated BP, cardiac hypertrophy, glucose
      intolerance, and increases in plasma glucose, insulin, free fatty acids (FFA),
      and angiotensin-converting enzyme (ACE) activity. They also showed increased
      protein kinase C betaII (PKC betaII) expression and oxidative stress in cardiac
      tissue. In plasma, decreased kallikrein enzyme activity and nitric oxide
      metabolites were observed, compared to control. Simultaneous treatment with CA
      (300 mg/Kg) mitigated these alterations. PKC betaII expression was similar to
      that of control; the rats displayed normal BP and ACE activity, enhanced
      antioxidant protection, and close to normal values of metabolic parameters. The
      BP-lowering effect of CA was abolished when CA-treated rats were administered L
      nitroarginyl methyl ester (L-NAME 6g/Kg). These observations suggest that the BP
      lowering action of CA in this model could be attributed to multiple and
      interrelated mechanisms, such as an increase in NO and kinin availability,
      reduction in PKC action, and antioxidant protection.

PMID- 18058478
TI  - Observational study of hypertension in Matelica, Italy (Matelica hypertension
      study).
AB  - This study summarizes the results of an epidemiological investigation carried out
      on the occasion of the Second World Hypertension Day (May 13, 2006) in the city
      of Matelica in the Region of the Marches, Central Italy. In all, 518 subjects
      (298 males, average age 52.3 years; 220 females, average age 55 years) with
      either diagnosed hypertension or who were thought to be normotensive had arterial
      blood pressure measured. Other cardiovascular risk factors and the costs of
      pharmacological treatment for hypertension were assessed as well. In 72.46% of
      examined subjects, arterial blood pressure levels averaged > or =140-90 mmHg if
      non-diabetic and > or =130-80 mmHg if diabetics. A total of 48.14% of individuals
      assumed in anamnesis to be normotensive had arterial blood pressure levels higher
      than the above values and were therefore found to have hypertensive values. The
      cost of anti-hypertensive treatment in the area of Matelica averages Euro
      543.7/patient/year. The present data, which are in line with those of other
      epidemiological studies performed in Italy, confirm the view that arterial
      hypertension control in Italy is still largely unsatisfactory. This observation
      should stimulate both health and specific medical measures to counter the risk of
      complications of arterial hypertension in aged populations, such as those present
      in the territory examined.

PMID- 18058479
TI  - Single-dose, randomized, crossover bioequivalence study of amlodipine maleate
      versus amlodipine besylate in healthy volunteers.
AB  - Amlodipine, marketed primarily as a besylate salt, is a calcium channel blocker
      used for treating essential hypertension. Amlodipine maleate is another salt that
      is considered, in terms of pharmacokinetics and pharmacodynamics, similar to
      amlodipine besylate. This open, randomized, two-period crossover trial has
      investigated in 24 healthy volunteers over a 144 h period the bioequivalence of
      amlodipine maleate tablets 10 mg versus amlodipine besylate tablets (Norvasc 10
      mg). Plasma amlodipine concentrations were assessed by ultra performance liquid
      chromatography interfaced with a double quadrupole mass spectrometer. The area
      under the curve total (AUC(t)) and the area under the curve to infinity
      (AUC(inf)) values, peak plasma concentration (C(max)), and time to attain peak
      (t(max)) were not statistically different between the two drugs. AUC(t) and
      AUC(inf) values were higher (p < 0.05) in females than in males. The tolerability
      profile was comparable for the two salts of amlodipine. These findings indicate
      that amlodipine maleate and besylate are bioequivalent and were well tolerated,
      which suggests that the plasma kinetics of amlodipine depend on the properties of
      the molecule itself. Hence, the two salts investigated could be used
      interchangeably in clinical practice.

PMID- 18058480
TI  - Persistence on treatment and blood pressure control with different first-line
      antihypertensive treatments: a prospective evaluation.
AB  - We enrolled 347 hypertensive patients, randomly allocated them to different first
      line treatments, and followed-up for 24 months. Persistence on treatment was
      significantly higher in patients treated with ARBs (68.5%) and ACE inhibitors
      (64.5%) vs. CCBs (51.6%), beta-blockers (44.8%), and diuretics (34.4%). No ARB,
      ACE inhibitor, beta-blocker, or diuretic was associated with a greater
      persistence in therapy as compared with the other molecules used in each
      therapeutic class. The rate of persistence was significantly higher in patients
      treated with lercanidipine vs. other CCBs (59.3% vs. 46.6%). Systolic and
      diastolic BP decreased more in patients treated with ARBs (-11.2/-5.8 mmHg), ACE
      inhibitors (-10.5/-5.1 mmHg), and CCBs (-8.5/-4.6 mmHg) when compared to beta
      blockers (-4.0/-2.3 mmHg) and diuretics (-2.3/-2.1 mmHg).

PMID- 18058481
TI  - Blood pressure and serum potassium levels in hypertensive patients receiving or
      not receiving antihypertensive treatment.
AB  - OBJECTIVE: Serum potassium has a fundamental role in blood pressure (BP)
      regulation, and there is evidence highlighting the importance of potassium
      homeostasis in hypertension. The aim of this study was to determine the
      relationship between serum potassium levels and office BP in untreated essential
      hypertensives and the effect of antihypertensive medication on serum potassium
      levels. SETTING AND PARTICIPANTS: In a retrospective analysis, we collected data
      for consecutive patients first visiting our Hypertension Clinic from 1999-2004.
      From this population, we first selected patients who were not taking any
      antihypertensive medication. Patients who had conditions that could affect
      potassium metabolism, such as history of arrhythmias treated with digitalis,
      diabetes mellitus under insulin treatment, and hypo- and hyperthyroidism, were
      excluded from the study. From the remaining patients, those who had impaired
      renal function (serum creatinine > or = 1.6 mg/dL for men and > or = 1.4 mg/dl
      for women) and patients with secondary forms of hypertension were also excluded.
      The final population consisted of 817 subjects. Multivariate linear regression
      analysis was applied, and models were created associating serum potassium with
      systolic BP, diastolic BP, mean BP, or pulse pressure. The population for the
      second part of the study consisted of patients first visiting our Hypertension
      Clinic who were on one antihypertensive agent. This second group included 757
      patients, 218 of whom were on beta-blockers, 42 on diuretics, 187 on angiotensin
      converting enzyme (ACE) inhibitors, 287 on calcium channel blockers (CCBs), and
      28 on angiotensin receptor blockers (ARBs). RESULTS: After adjusting for age,
      gender, and body mass index, significant negative correlations were found between
      serum potassium levels and systolic BP (R = -0.093, p = 0.007), diastolic BP (R =
      -0.078, p = 0.03), mean BP (R = -0.122, p = 0.002), and pulse pressure (R = 
      0.071, p = 0.044). The levels of potassium were found to be significantly lower
      among patients receiving diuretics than those receiving one of the other four
      drug categories of antihypertensive (p < 0.05 for beta-blockers, ACE inhibitors,
      and CCBs; p < 0.001 for ARBs). In addition, hypokalemia was found to be
      significantly more prevalent in the group using diuretics than the other groups.
      CONCLUSIONS: The observed reverse relation between serum potassium and BP
      supports a close pathophysiological connection between serum potassium and
      essential hypertension. Moreover, diuretic therapy is a significant cause of
      hypokalemia and requires systematic monitoring.

PMID- 18058482
TI  - Comparative crossover, randomized, open-label bioequivalence study on the
      bioequivalence of two formulations of thioctic acid in healthy volunteers.
AB  - An open-label, randomized, crossover single-dose study, using two periods and two
      sequences with a washout period of seven days was conducted to assess the
      comparative bioavailability of thioctic (alpha-lipoic) acid (ALA) 600 mg
      formulation and that of a reference formulation. Blood samples were collected up
      to +6 h post dosing, the plasma was separated, and thioctic acid concentrations
      were determined by high-performance liquid chromatographic method with single
      mass spectrometry detection (HPLC-MS) and a lower limit of quantification of
      190.1 ng/ml. Mean values of the individual C(max) were 1338.6 +/- 751.8 ng/ml and
      1215.8 +/- 560.5 ng/ml for the test and reference preparations, respectively.
      Mean +/- standard deviation (SD) total area under the curve up to the last
      measurable concentration (AUC(t)) was 3510.9 +/- 1088.6 ng x h/ml for the test
      formulation and 3563.5 +/- 1374.1 ng x h/ml for the reference formulation. Mean
      +/- SD total area under the curve (AUC(inf)) was 6925.6 +/- 4045.8 ng x h/ml for
      the test formulation and 7797.1 +/- 5963.1 ng x h/ml for the reference
      preparation. Terminal elimination half-life was 5.68 +/- 5.05 h for the test and
      6.11 +/- 6.15 h for the reference formulations. Time of maximum concentration
      (t(max)) was 1.24 +/- 1.23 h for the test and 2.05 +/- 1.21 h for the reference
      formulations. Ninety percent confidence intervals were comprised within the
      bioequivalence acceptance criteria (80-125%) for all of the parameters analyzed
      except t(max). The comparison between males and females showed no significant
      difference for the two drug treatment.

PMID- 18058483
TI  - Heart-rate variability as a quantitative measure of hypnotic depth.
AB  - The authors investigated whether heart-rate variability can serve as a device for
      real-time quantitative measurement of hypnotic depth. This study compared the
      continuous self-rated hypnotic depth (SRHD) of 10 volunteers with heart rate,
      amplitude, and frequency changes from a time-frequency analysis of heart-rate
      variability (HRV). The authors found significant linear relationships between
      SRHD and the high-frequency (HF) component of HRV. Specifically, SRHD was
      correlated negatively with the frequency of the HF component and positively with
      the amplitude of the HF component. Unexpectedly, the average temporal trend in
      SRHD fit well (R(2) = .99) to the step response of a first-order system with a 4
      minute time constant. The findings suggest that the reactivity of the
      parasympathetic branch of the autonomic nervous system reflected in HRV could
      become part of a real-time, quantitative measure of hypnotic depth.

PMID- 18058484
TI  - Healthy narcissism and ego state therapy.
AB  - The term narcissism is often pejorative and associated with the diagnosis of
      narcissistic personality disorder. However, some degree of narcissism can be
      viewed as essential when considering the ingredients of a healthy personality.
      The ego state literature contains references to the maturation of ego states, the
      creation of helpful ego states, transformation of the function of ego states, and
      the strengthening of healthy ego states as components of the development of a
      "harmonious family of self." For an individual to develop healthy narcissism and
      eventually self-esteem, it's assumed that these ego state interventions are
      involved and produce changes in internal psychic structure. This article explores
      theories and therapy regarding the development of healthy narcissism, self
      esteem, and a well-functioning sense of entitlement. Case material is summarized
      to illustrate how ego state therapy can be an important part of this process.

PMID- 18058485
TI  - Hypnosis and thought suppression - more data: a brief communication.
AB  - This study hypothesized that hypnosis would enhance thought suppression by
      minimizing the effect of cognitive load. Twenty-eight high and 29 low
      hypnotizable hypnotized participants received the cognitive load of learning a 6
      digit number. Participants then received either a suppression instruction or no
      instruction for a personal memory of a failure experience. Thought-suppression
      effectiveness was indexed by measures of self-report monitoring, competition of
      scrambled sentences, and facial electromyography. Low hypnotizable participants
      who received the suppression instruction displayed postsuppression rebound on the
      sentence-unscrambling task. In contrast, high hypnotizable participants did not
      display any rebound effects. These findings support the proposition that hypnosis
      facilitates thought suppression.

PMID- 18058486
TI  - Examining hypnosis legislation: a survey of the practice in Israel.
AB  - Hypnosis as a therapeutic technique bears potential risks when carried out
      inexpertly. Because of this, Israel was the first to legislate hypnosis. This
      study examines the current state of clinical hypnosis practice in Israel. A
      questionnaire was sent to 470 licensed hypnotists and 1250 unlicensed
      professionals; 478 (25.7%) of the 1720 potential respondents returned the
      questionnaires. Of these, 249 (51.8%) were licensed hypnotists, and 232 (48.2%)
      were unlicensed. Of the unlicensed professionals, 45% reported practicing
      hypnosis; 50% of them practice hypnosis with adolescents and 41.2% with children.
      Many of them practice hypnosis in public clinics (71.6%). Of the licensed
      professionals, 94.4% reported practicing hypnosis in the course of their clinical
      work. The authors conclude that great number of unlicensed hypnotists carry on
      clinical practice of hypnosis and suggest steps to increase the efficiency of the
      law as part of a regulatory system.

PMID- 18058487
TI  - Hypnosis as an adjunct therapy in the management of diabetes.
AB  - Although diabetes is one of the most serious global health problems, there is no
      real cure yet for it. The conventional insulin treatment programs aimed at life
      quality improvement do not take into account the psychological aspects of the
      disease. Because diabetes has important psychological components, it seems
      reasonable to consider hypnosis as an adjunct therapy for diabetes. This paper
      examines the empirical literature on the effectiveness of hypnosis in the
      management of diabetes, including regulation of blood sugar, increased
      compliance, and improvement of peripheral blood circulation. Despite some
      methodological limitations, the literature shows promising results that merit
      further exploration. Multimodal treatments seem especially promising, with
      hypnosis as an adjunct to insulin treatments in the management of both Type 1 and
      Type 2 diabetes for stabilization of blood glucose and decreased peripheral
      vascular complications.

PMID- 18058488
TI  - Language, mysticism, and hypnotizability: a brief communication.
AB  - People attempting to communicate religious and mystical experiences tend to use
      the same language strategies employed in inducing hypnotic trance. Both
      incorporate vague language that provides receptive listeners the opportunity to
      insert their own content. This study examines whether people who have had
      mystical or religious experiences are also more likely to respond to the language
      of hypnosis. Eighty-one participants completed the Harvard Group Scale of
      Hypnotic Susceptibility, Form A and the Hood Mysticism Scale. Participants were
      divided into 3 equal groups based on "high," "ambiguous," and "low" mysticism
      scale scores. The high group scored significantly higher on hypnotizability
      compared to the low group. The relationship between openness to mystical and
      religious experience and susceptibility to hypnotic suggestion warrants further
      investigation.

PMID- 18058489
TI  - Responding and failing to respond to both hypnosis and a kinesthetic illusion,
      Chevreul's Pendulum.
AB  - In this study, participants who failed to exhibit pendulum movement in response
      to Chevreul's Pendulum (CP) instructions had lower Stanford Hypnotic
      Susceptibility Scale, Form A (SHSS:A) scores and reported experiencing less
      subjective response to hypnosis than did their counterparts who exhibited CP
      movement. However, intensity scores on Shor's Personal Experiences Questionnaire
      (PEQ) did not differ between pass- and fail-CP groups. Additionally, pass-CP
      participants showed positive correlations between PEQ intensity scores and
      hypnotizability scores, while fail-CP participants showed negative correlations
      among these measures. These findings are consistent with the notion that CP
      failure may reflect a situation-specific unwillingness to become imaginatively
      involved rather than a general inability to do so. Additional analyses revealed
      that 5 of 10 participants who had failed the CP task scored 0 or 1 on the SHSS:A,
      while only 3 of 65 pass-CP participants scored 0 or 1.

PMID- 18058490
TI  - Genetics and neuroimaging of attention and hypnotizability may elucidate placebo.
AB  - Attention binds psychology to the techniques of neuroscience and exemplifies the
      links between brain and behavior. Associated with attentional networks, at least
      3 brain modules govern control processes by drawing on disparate functional
      neuroanatomy, neuromodulators, and psychological substrates. Guided by data
      driven brain theories, researchers have related specific genetic polymorphisms to
      well-defined phenotypes, including those associated with different attentional
      efficiencies and hypnosis. Because attention can modulate both cognitive and
      affective processes, genetic assays together with neuroimaging data have begun to
      elucidate individual differences. Findings from genetic assays of both attention
      and hypnotizability pave the way to answering questions such as how high
      hypnotizable individuals may differ from less-hypnotizable persons. These
      exploratory findings may extend to the identification of placebo responders.

PMID- 18058492
TI  - A role for denial in poor adherence to psoriasis treatment.

PMID- 18058493
TI  - The enigma of rosacea.
AB  - This short paper reviews the nature of rosacea emphasizing the possibility of a
      solar cause. The sites of involvement and the physical signs of rosacea including
      the flushing, the erythema and the telangiectasia as well as the intermittent
      episodes of inflammation with swelling and papules may all be explained by UVR
      induced damage to dermal connective tissue. The dermal damage permits vaso
      dilation and vascular pooling.

PMID- 18058494
TI  - Impact of adalimumab treatment on patient-reported outcomes: results from a Phase
      III clinical trial in patients with moderate to severe plaque psoriasis.
AB  - OBJECTIVE: The effect of adalimumab on patient-reported outcomes (PROs) was
      evaluated in patients with moderate to severe psoriasis during the initial 16
      week, double-blind period of a 52-week, Phase III, multicenter trial. METHODS:
      Patients were randomized to placebo or adalimumab 80 mg at Week 0 and 40 mg every
      other week from Week 1 to Week 15. PROs were evaluated throughout the study and
      included the Dermatology Life Quality Index (DLQI), the Short Form 36 Health
      Survey (SF-36), the Work Productivity and Activity Impairment Questionnaire
      Specific Health Problem (WPAI-SHP), and several patient-rated symptom scales.
      RESULTS: The adalimumab-treated group reported significantly greater improvements
      in DLQI total score (p<0.001), SF-36 Physical Component Summary score (p<0.001),
      and Mental Component Summary score (p<0.001) compared with the placebo-treated
      group over 16 weeks. Significant differences, favoring adalimumab, were also seen
      for the DLQI subscale scores (p < 0.001); SF-36 scale scores (p<0.001); WPAI-SHP
      work impairment (p<0.001), activity limitation (p<0.001), and overall work
      impairment scores (p<0.001); patient's global assessment of disease severity
      (p<0.001), psoriasis pain (p<0.001), and psoriasis-related pruritus (p = 0.002).
      CONCLUSION: Adalimumab was efficacious in improving dermatology-specific and
      general health-related quality of life, work and activity limitations, and
      psoriasis-related symptoms in patients with moderate to severe psoriasis over a
      16-week period.

PMID- 18058495
TI  - Management of complications following leprosy: an evolving scenario.
AB  - Reaction in leprosy, nerve damage/deformities, drug resistance/relapses, may come
      as yet another challenge. Their management too is intriguing and has been dealt
      with carefully. In addition, special situations such as pregnancy and concomitant
      HIV/tuberculosis also need care for their effective management. To facilitate a
      comprehensive appraisal, the subject has been bifurcated into management of
      leprosy per se were multidrug therapy (MDT) is widely the accepted and acclaimed
      treatment option. The former has been dealt with in depth in an adjoining
      article, while the latter forms the contents of the current paper. The salient
      contents of the text are illustrated by exemplary literature, which should
      provide an adequate and comprehensive source of information for the academic work
      force, under- and post-graduate students of dermatology, health workers and
      treating physicians involved in the care of leprosy patients, and facilitate
      decision making or options for treatment in a given case.

PMID- 18058496
TI  - Basic fibroblast growth factor treatment for various types of recalcitrant skin
      ulcers: reports of nine cases.
AB  - The treatment of chronic intractable ulcers constitutes crucial topics in
      dermatological practice. We describe here nine cases of different types of
      therapy-resistant ulcers that were successfully treated with the employment of
      spraying with basic fibroblast growth factor once daily. When it was initiated,
      we could easily find in all the cases that the healing process of the ulcers was
      greatly accelerated by this therapy with the resultant achievement of complete
      epithelialization in a relatively short time. This therapeutic modality is useful
      not only for chronic ulcers but also for acute extensive ulcers.

PMID- 18058498
TI  - Synthesis of fluorinated indoles as RNA analogues.
AB  - Nucleoside analogues are chemical means to investigate hydrogen bonds, base
      stacking, and solvation as the three predominant forces that are responsible for
      the stability of secondary structure of nucleic acids. To obtain deeper insight
      into the contributions of these interactions to RNA stability apart from the ones
      exerted by the predominant nucleosides we decided to synthesize some novel
      nucleic acid analogues where the nucleobases are replaced by fluoroindoles.
      Fluorinated indoles can be compared to fluorinated benzimidazoles to determine
      the role of nitrogen in five membered ring system. The synthesis of fluoroindole
      ribonucleosides is described here.

PMID- 18058499
TI  - Different strategies for the synthesis of 2'-O-aminoethyl adenosine building
      blocks.
AB  - The chemical modification of the 2'-O-position of nucleosides proved to be of
      great importance for the RNA stability. Greater stability of RNA duplexes allows
      a longer half life in the cell and, therefore, a better effect of RNA
      Interference. Here we investigated the synthesis of 2'-O-aminoethyl adenosine as
      a cationic modified building block.

PMID- 18058500
TI  - A phenanthrene modified RNA hairpin.
AB  - The influence of hairpin loop replacement with the phenanthrene moiety in RNA was
      investigated. The stability of this novel structure was compared to a hairpin
      with a U(4) loop, an extra stable tetra-loop (UUCG), and an analogous
      phenanthrene modified DNA hairpin. Thermal denaturation experiments and CD
      spectra were used to study the structure and stability of the modified hairpin.

PMID- 18058501
TI  - Aldehydic oligonucleotide: a key intermediate for the preparation of
      oligonucleotide conjugates through oxime bond formation.
AB  - Oligonucleotides functionalized with an aldehyde group are the key intermediates
      used for the preparation of peptide-oligonucleotide conjugates through the
      formation of an oxime linkage. Herein, we describe a brief overview of various
      synthetic protocols developed in our laboratory for the preparation of aldehyde
      containing oligonucleotides and their subsequent conjugation with peptides.

PMID- 18058502
TI  - Microwave-assisted ribosylation of modified heterocyclic bases by Vorbruggen
      method.
AB  - During the last decades the nucleoside synthesis has proven to be important. The
      modified silyl-Hilbert-Johnson nucleoside synthesis modified by Vorbruggen is one
      of the most often used methods. We have studied N-glycosilation of modifieded
      heterocyclic bases by Vorbruggen method with microwave irradiation and we were
      able to shorten the reaction time and obtain higher yields. The method was
      demonstrated by fluoroquinolone and purine.

PMID- 18058503
TI  - Acid-mediated cleavage of oligonucleotide P3' --> N5' phosphoramidates triggered
      by sequence-specific triplex formation.
AB  - The P-N bond in oligonucleotide P3' --> N5' phosphoramidates (5'-amino-DNA) is
      known to be chemoselectively cleaved under mild acidic conditions. We prepared
      homopyrimidine oligonucleotides containing 5'-amino-5'-deoxythymidine (5'-amino
      DNA thymine monomer) or its conformationally locked congener, 5'-amino-2',4'-BNA
      thymine monomer, at midpoint of the sequence. The effect of triplex formation
      with homopurineohomopyrimidine dsDNA targets on acid-mediated hydrolysis of the
      P3' --> N5' phosphoramidate linkage was evaluated. Very interestingly, it was
      found that the triplex formation significantly accelerates the P-N bond cleavage.

PMID- 18058504
TI  - 5'-carbamoylphosphonyl-[6-3H]-AZT as a tool for studying metabolic
      transformations of the nonradioactive counterpart, an inhibitor of HIV
      replication.
AB  - An effective synthesis of 5'-carbamoylphosphonyl-[6-3H]-AZT was developed from [6
      3H]-AZT. For the synthesized compound, chemical and enzymatic stability were
      determined and its penetration across HL-60 cell membranes was studied.

PMID- 18058505
TI  - DNA containing non-nucleosidic phenanthrene building blocks with asymmetrical
      linkers.
AB  - The synthesis and hybridization properties of oligonucleotides containing
      phenanthrene building blocks with non-nucleosidic linkers of different length are
      described. It was found that the length of the linkers, as well as the
      combination of unequal linkers can have a substantial influence on the thermal
      stability of the modified DNA.

PMID- 18058506
TI  - An enzymatic transglycosylation of purine bases.
AB  - An enzymatic transglycosylation of purine heterocyclic bases employing readily
      available natural nucleosides or sugar-modified nucleosides as donors of the
      pentofuranose fragment and recombinant nucleoside phosphorylases as biocatalysts
      has been investigated. An efficient enzymatic method is suggested for the
      synthesis of purine nucleosides containing diverse substituents at the C6 and C2
      carbon atoms. The glycosylation of N(6)-benzoyladenine and N(2)-acetylguanine and
      its O(6)-derivatives is not accompanied by deacylation of bases.

PMID- 18058507
TI  - Design, enantiopure synthesis, and biological evaluation of novel iso-D-2',3'
      dideoxy-3'-fluorothianucleoside derivatives as a bioisostere of lamivudine.
AB  - Novel iso D-2',3'-dideoxythianucleoside derivatives 1-3 were designed and
      asymmetrically synthesized to search for new anti-HIV agents. Final compounds 1-3
      were evaluated against a variety of viruses including HIV-1 and 2. Only cytosine
      analog 3 showed a potent anti-VSV activity (EC(50) = 9.43 microg/mL). This result
      implies that iso 2',3'-dideoxy sugar templates might play a role of a sugar
      surrogate of nucleosides for the development of anti-RNA virus agent.

PMID- 18058508
TI  - New analogs of acyclovir substituted at the side chain.
AB  - A series of novel analogs of acyclovir, substituted with an alkyl (methyl, ethyl,
      n-butyl) or phenyl group at the positions 1', 4', and/or 5', has been obtained in
      a direct one-pot coupling reaction of guanosine and the respective 1,3
      dioxolanes. The new acyclonucleosides were essentially inactive in antiviral
      (HSV, VV, VSV, HBV) evaluation in vitro.

PMID- 18058509
TI  - Synthesis of anthraquinone oligonucleotides for triplex stabilization.
AB  - The synthesis of two anthraquinone phosphoramidites is described. In both cases
      the anthraquinone moiety is attached via a linker to the 5-position of a uracil
      base, allowing incorporation at any thymidine position in an oligonucleotide
      sequence. Anthraquinone-modified oligonucleotides have potential applications as
      triplex stabilizers and fluorescence quenchers.

PMID- 18058510
TI  - Clip-phen conjugates for the specific cleavage of nucleic acids.
AB  - For the first time Clip-Phen (1) was conjugated to oligonucleotides to provide
      very efficient tools for the cleavage of nucleic acids at specific positions. The
      synthesis of the conjugates as well as the cleavage experiments are reported.

PMID- 18058511
TI  - OligoPrep PVA support for oligonucleotide synthesis in columns on a scale up to
      10 micromol.
AB  - OligoPrep is a macroporous polyvinylacetate (PVA) biodegradable support that has
      been designed for cost-effective automated synthesis of oligonucleotides using
      standard phosphoramidite chemistry. Originally developed for large-scale
      oligonucleotide synthesis in beds and reactors, we present here its utility for
      medium-scale work of 1-10 micromol in column syntheses on standard DNA
      synthesizers. We show how an increase in scale, and, therefore, yield, can be
      achieved without significant increase in reagent quantity. Additional deblock and
      oxidation cycles can provide high coupling yields, and the use of concentrated
      ammonia in aqueous methylamine (AMA) for oligonucleotide cleavage and
      deprotection results in excellent recovery.

PMID- 18058512
TI  - A new and short convergent synthetic strategy to carbocyclic nucleosides.
AB  - An efficient synthesis for racemic cyclopent-3-en-1-yl nucleoside analogues has
      been developed starting from cyclopentadiene. The key step is the regioselective
      hydroboration of a mixture of intermediate alkylatede cyclopentadienes to give
      one cyclopentenol.

PMID- 18058513
TI  - Oligonucleotide charge reversal: 2'-O-lysylaminohexyl modified oligonucleotides.
AB  - A novel cationic building nucleoside building block designed for antisense and
      siRNA oligonucleotides is presented. Protected L-lysine was coupled to 2'-O
      aminohexyluridine and the resulting nucleoside was phosphitylated for automated
      oligonucleotide synthesis. An increasing number of these 2'-O-lysylaminohexyl
      nucleosides lowered the melting temperature of desoxy-thymidine homododecamers,
      but the decrease was lower than that for DNA/RNA hybrids. Incubation with an
      exonuclease showed the exceptionally high resistance against enzymatic
      degradation. CD spectrometry revealed a gradual transition towards an A-type
      oligonucleotide structure. Based on these data, the cationic building block is
      particularly suited for gapmer antisense as well as siRNA oligonucleotides.

PMID- 18058514
TI  - Asymmetric synthesis of apio fluoroneplanocin A analogs as potential AdoHcy
      hydrolase inhibitor.
AB  - Apio fluoroneplanocin A (apio F-NPA, 3) and its uracil analogue 4 have been
      designed and asymmetrically synthesized starting from D-ribose. Introduction of
      fluoro group into vinylic position of 5 was accomplished successfully over 5
      steps employing key reactions such as iodination according to an addition
      elimination reaction mechanism, stereo- and regioselective reduction of
      alpha,beta-unsaturated ketone, and electrophilic fluorination. This methodology
      can be adapted to the synthesis of fluoro compounds extensively.

PMID- 18058515
TI  - Hairpin mimics with phenanthroline- and bipyridine-derived linkers.
AB  - The synthesis and structural stabilities of modified oligonucleotide hairpins
      containing phenanthroline- and bipyridine-modified loops is reported.
      Phenanthroline (phen) and bipyridine (bipy) building blocks were synthesized,
      incorporated into DNA-oligonucleotides, and analyzed by thermal denaturation
      experiments. The so modified oligomers were found to form stable hairpin
      structures. Tm values were not affected by divalent transition metals.

PMID- 18058517
TI  - A general route to D- and L-six-membered nucleoside analogues.
AB  - A simple synthetic route for novel L-(as well as D-) six-membered nucleosides is
      described. Particularly, we have provided a general approach to the synthesis of
      azasugar-based nucleosides, which preparation has been easily achieved starting
      from the coupling of our three carbon homologating agent 1 with the well known
      Garner aldehyde 4. Further suitable and stereocontrolled functionalizations of
      the intermediate 9 will provide, after the base insertion, a wide class of six
      membered modified azanucleosides to be tested as NRTIs.

PMID- 18058516
TI  - Inhibition of HIV-1 replication in macrophages by red blood cell-mediated
      delivery of a heterodinucleotide of lamivudine and tenofovir.
AB  - Homo- and heterodimers of nucleoside/nucleotide analogues as reverse
      transcriptase inhibitors are effective on HIV-1-infected human monocyte-derived
      macrophages (M/M) compared to the single drugs or their combination. Since the
      combined treatment of lamivudine (3TC) and tenofovir ((R)PMPA) has an
      antiretroviral efficacy and a synergic effect respect to separate drugs, the
      heterodinucleotide 3TCpPMPA was synthesized. A single administration of the dimer
      as free drug or 3TCpPMPA-loaded RBC selectively targeted to M/M was able to
      almost completely protect macrophages from "de novo" infection.

PMID- 18058518
TI  - New developments in the synthesis of oligonucleotide-peptide conjugates.
AB  - The stability of oligodeoxynucleotides to trifluoroacetic acid is studied.
      Pyrimidine oligonucleotides were stable in the conditions used for the removal of
      t-butyl groups. Oligonucleotide-3'-peptide conjugates carrying pyrimidine
      oligonucleotides are prepared stepwise using peptide-supports and Fmoc, t-butyl
      strategy. Using this strategy we have prepared an oligonucleotide-peptide
      conjugate containing as peptide the leucine-rich fragment of FOS, a transcription
      factor involved in many important cellular processes. This conjugate has a long
      peptide sequence with a large number of trifunctional amino acids.

PMID- 18058519
TI  - Kinetics of binding of multisubstrate analogue inhibitor (2-amino-9-[2
      (phosphonomethoxy)ethyl]-6-sulfanylpurine) with trimeric purine nucleoside
      phosphorylase.
AB  - Complex formation of multisubstrate analogue inhibitor--2-amino-9-[2
      (phosphonomethoxy)ethyl]-6-sulfanylpurine (PME-6-thio-Gua) with trimeric purine
      nucleoside phosphorylase from Cellulomonas sp. was investigated using a stopped
      flow spectrofluorimetric approach. Results obtained indicate that, in contrast to
      binding of guanine, i.e., the transition-state conformation trapping ligand, for
      which binding at each active site is followed by the enzyme conformational
      change, association of the ground-state analogue PME-6-thio-Gua is a one-step
      process.

PMID- 18058520
TI  - Synthesis of enantiopure pseudo-L-vinylcyclopropyl nucleosides bearing quaternary
      carbon as potential anti-herpesvirus agent.
AB  - Pseudo-L-vinylcyclopropyl adenine and guanine nucleosides 11 and 12 were designed
      and enantiopurely synthesized starting from (S)-epichlorohydrin using tandem
      alkylation, regioselective oxirane-ring opening, and chemoselective reduction as
      key steps.

PMID- 18058521
TI  - Triplex formation using oligonucleotide clamps carrying 8-aminopurines.
AB  - The synthesis and properties of triplex-forming DNA clamps carrying 8
      aminopurines are described. The stability of triple helices is enhanced by
      replacing purine bases with 8-aminopurine residues. These enhanced binding
      properties are used for the specific capture of polypyrimidine RNA/DNA sequences
      of interest.

PMID- 18058522
TI  - Synthesis of 2',3'-dideoxyinosine via radical deoxygenation.
AB  - A synthetic method for 2',3'-dideoxyinosine (ddI) from inosine was established
      via radical deoxygenation of N1,5'-O-diprotected-2',3'-bis-S-methyl
      dithiocarbonate of inosine derivatives. The radical deoxygenation proceeded
      smoothly to give the desired dideoxy compounds in good yields using 1
      ethylpiperidinium hypophosphite and triethylborane. Benzyl or p-methoxybenzyl
      protection of inosine at the N1, 5'-O-positions were effective for the ddI
      synthesis.

PMID- 18058523
TI  - Inhibitory properties of nucleotides with difluoromethylenephosphonic acid as a
      phosphate mimic versus calf spleen purine nucleoside phosphorylase and effect of
      these analogues on the viability of human blood lymphocytes.
AB  - Several cyclic and acyclic 6-keto purine nucleotides with
      difluoromethylenephosphonic acid as phosphate mimic are proved to be potent
      inhibitors of mammalian purine nucleoside phosphorylase (PNP). Antiproliferative
      activity of these analogues on the growth of human blood lymphocytes was tested
      by MTT assay. Compared to inhibitory effects on the growth of human blood T
      lymphocytes isolated from healthy donors, all analogues significantly slow down
      proliferation of T-lymphocytes isolated from patients with autoimmune thyroid
      disease--Hashimoto's thyroiditis.

PMID- 18058524
TI  - Nucleolipids as potential organogelators.
AB  - Four different series of nucleolipids or bola-nucleolipids were synthesized or re
      synthesized. Most of the compounds were studied with respect to their gelation
      properties toward either water or aromatic, hetero-aromatic, and aliphatic
      hydrocarbons. Bola-nucleolipids 6 and 7 do not gelate any solvent tested, neither
      as sole additive nor by adding up to 10 wt% of a 1:1 mixture. The nucleolipid 22
      carrying the antiviral acyclovir as a head group proved to be a potent
      organogelator for aromatic hydrocarbons such as toluene, but not for hetarenes,
      aliphatic hydrocarbons or water. The mono-tailed nucleolipid 24 exhibits
      excellent organogelator properties for both aromatic and aliphatic hydrocarbons.
      These were studied as a function of concentration and temperature.

PMID- 18058525
TI  - Asymmetric synthesis of novel pseudo-D-vinylcyclopropyl nucleosides bearing
      quaternary carbon as potential anti-herpesvirus agent.
AB  - Pseudo-D-vinylcyclopropyl nucleosides 10-12 bearing a quaternary carbon were
      designed and synthesized starting from (R)-epichlorohydrin using a tandem
      reaction of double alkylation and lactonization via oxirane-ring opening
      reaction, a Wittig reaction, and chemoselective reduction as potential anti
      herpesvirus agent.

PMID- 18058526
TI  - Photoinduced crosslinking of double-helical DNA by psoralen covalently linked to
      a triple helix-forming oligonucleotide under near-physiological conditions.
AB  - Stable triplexes have been generated under near-physiological conditions by the
      introduction of the C and T base analogues 3-methyl-2-aminopyridine-2'
      deoxyriboside and 5-(3-aminoprop-2-ynyl)-'-deoxyuridine into psoralen-conjugated
      triplex-forming oligonucleotides. After irradiation with UV light at 365 nm,
      photo-induced cross-linking of the TFO to double-helical DNA was observed by UV
      melting analysis and fluorescence measurements.

PMID- 18058527
TI  - Stereoselective synthesis of 1'-functionalized-4'-thionucleosides.
AB  - Stereoselective functionalization of the 1'-position of 4'-thionucleosides was
      achieved using a stereoselective S(N)2 reaction controlled by 5-membered ring
      coordination.

PMID- 18058528
TI  - O2,1'-anhydro-(beta-D-psicofuranosyl)thymine and 1-(1',4'-O-anhydro-beta-D
      psicofuranosyl)thymine: the crystal structures versus the 1H NMR and ab initio
      data.
AB  - The crystal structures of the title compounds 1 and 2 have been determined.
      Relation between the stereochemistry of both nucleosides in the crystal state and
      the (1)H NMR data in solution as well as the ab initio calculations is discussed.

PMID- 18058529
TI  - Asymmetric synthesis of cyclopropyl-fused 2'-C-methylcarbanucleosides as
      potential anti-HCV agents.
AB  - Novel 2'-C-methyl-cyclopropyl-fused carbocyclic nucleosides as potential anti-HCV
      agents were stereoselectively synthesized, utilizing regioselective cleavage of
      the isopropylidene group and cyclic sulfate chemistry as key steps.

PMID- 18058530
TI  - Syntheses of pyrimidine acyclic nucleoside phosphonates as potent inhibitors of
      thymidine phosphorylase (PD-ECGF) from SD-lymphoma.
AB  - In the present study, we synthesized a series of pyrimidine acyclic nucleoside
      phosphonates bearing a number of substituents in C-5 position of uracil moiety
      and in the N-1-side chain. In addition, we have investigated in particular the
      novel syntheses of fluorinated derivatives substituted in the N-1-side chain and
      uracil C-5 position because fluorine-containing substituents are often powerful
      modifiers of chemical and biological properties. The obtained compounds exhibit a
      considerable inhibitory potency of thymidine phosphorylase from SD-lymphoma. In
      contrast, the synthesized phosphonates are not efficient inhibitors of E. coli
      and human thymidine phosphorylase.

PMID- 18058531
TI  - Diastereoselective synthesis of 2',3'-dideoxy-beta-C-glucopyranosides as
      intermediates for the synthesis of 2',3'-dideoxy-beta-D-glucopyranosyl-C
      nucleosides.
AB  - An extension of the Vorbruggen method of nucleotide synthesis for the synthesis
      of C-glucopyranosides, as intermediates for C-nucleosides, is described. It could
      be shown that the diastereoselectivity of the reaction can be tuned by a simple
      change of protecting groups.

PMID- 18058532
TI  - Studies on thermal stability of human cytidine deaminase.
AB  - The thermal stability of human cytidine deaminase (CDA), an enzyme involved in
      pyrimidine metabolism was investigated. With this in view, the residues R68 and
      Y60, supposed to be involved in the intersubunit interactions and in the
      catalytic site of CDA, were mutated to glutamine and glycine, respectively.
      Thermal stability experiments were performed on the purified mutants by means of
      circular dichroism and enzymatic assays. The results obtained should be useful
      for designing more efficient cytidine based drugs for chemotherapy.

PMID- 18058533
TI  - The effects of nucleoside analogues on promoter methylation of selected tumor
      suppressor genes in MCF-7 and MDA-MB-231 breast cancer cell lines.
AB  - The effects of 2-chloro-2'-deoxyadenosine, 9-beta-D-arabinofuranosyl-2
      fluoroadenine, and 5-aza-2'-deoxycytidine on promoter methylation of the selected
      tumor suppressor genes (i.e., ERalpha, BRCA1, RARbeta2, E-cadherin, PTEN, and
      APC) were estimated using methylation-sensitive restriction analysis. The studies
      were carried out in hormone-responsive, low-invasive cell line MCF-7 and hormone
      insensitive, highly invasive cell line MDA-MB-231. The results demonstrate an
      implication of the tested adenosine analogues and 5-aza-dCyd in regulation of DNA
      methylation process. Moreover, the effects of nucleoside analogues on PTEN
      promoter methylation suggest distinct mechanism of regulation of the epigenetic
      DNA modification in low-invasive compared to highly invasive breast cancer cells.

PMID- 18058534
TI  - ODN-based drugs for targeting of extracellular proteins.
AB  - In this work a novel approach to identify new therapeutic targets consisting of
      serum proteins which contain an oligonucleotide binding domain is presented.

PMID- 18058535
TI  - Novel S-ribosylhomocysteine analogues as potential inhibitors of LuxS enzyme.
AB  - Selective cross-coupling of the protected 6-fluoro-6-iodo-alpha-D-ribo-hex-5
      enofuranose with 2 equivalents of 4-ethoxy-4-oxobutylzinc bromide in the presence
      of Pd[P(Ph)(3)](4) followed by deprotections gave methyl 5,6,7,8,9-pentadeoxy-6
      fluoro-alpha/beta-D-ribo-dec-5(Z)-enofuranuronate; a S-ribosylhomocysteine
      analogue with the sulfur and carbon-5 atoms replaced by the fluoro(vinyl) unit.

PMID- 18058536
TI  - A new family of inhibitors of Mycobacterium tuberculosis thymidine monophosphate
      kinase.

PMID- 18058537
TI  - Investigation of novel lipid-functionalized PNA monomers as potential HIV-1 non
      nucleoside reverse transcriptase and/or integrase inhibitors.
AB  - A range of novel N-terminal lipid-functionalized peptide nucleic acid (PNA)
      monomers have been prepared and their abilities to inhibit HIV-1 reverse
      transcriptase and integrase have been examined.

PMID- 18058538
TI  - Telomere shortening in human HL60 cells by treatment with 3'-azido-2',3'
      dideoxynucleosides and telomerase inhibition by their 5'-triphosphates.
AB  - Telomerase is thought to play an important role in the mechanism of tumor cell
      immortalization by maintenance of telomere length. To obtain information on the
      susceptibility of telomerase to nucleoside analogues, the effects of base
      modified 3'-azido-2',3'-dideoxynucleoside triphosphates on the enzyme were
      investigated. It is suggested that the 2-amino group of the nucleotide purine
      nucleus is important for the inhibitory activity. Telomere shortening caused by
      long-term treatment with these nucleosides is also described.

PMID- 18058539
TI  - Troxacitabine prodrugs for pancreatic cancer.
AB  - Troxacitabine is a cytotoxic deoxycytidine analogue with an unnatural L
      configuration, which is activated by deoxycytidine kinase (dCK). The
      configuration is responsible for differences in the uptake and metabolism of
      troxacitabine compared to other deoxynucleoside analogues. The main drawback in
      the use of most nucleoside anticancer agents originates from their hydrophilic
      nature, which property requires a high and frequent dosage for an intravenous
      administration. To overcome this problem several troxacitabine prodrugs modified
      in the aminogroup with a linear aliphatic chain with a higher lipophilicity were
      developed. To determine whether these prodrugs have an advantage over
      Troxacitabine pancreatic cancer cell lines were exposed to Troxacitabine and the
      lipophilic prodrugs. The addition of linear aliphatic chains to troxacitabine
      increased sensitivity of pancreatic cancer cell lines to the drug > 100-fold,
      possibly due to a better uptake and retention of the drug.

PMID- 18058540
TI  - Synthesis of novel 2'-deoxy type trans-3',4'-bridged nucleic acid.
AB  - We newly designed and synthesized a 2'-deoxy type trans-3',4'-bridged nucleic
      acid (trans-3',4'-BNA) analogues bearing a 4,7-dioxabicyclo[4.3.0]nonane
      structure. The synthesis of the trans-3',4'-BNA was carried out successfully from
      thymidine over 21 steps. The structure of trans-3',4'-BNA was confirmed by x-ray
      crystallographic analysis, indicating that the furanose ring has a typical S-type
      conformation with C(3')-exo puckering.

PMID- 18058541
TI  - Furano- and pyrrolo [2,3-d] pyrimidine nucleosides and their 5'-O-triphospates:
      synthesis and enzymatic activity.
AB  - A series of bicyclic [2,3-d]furano- and pyrrolopyrimidine ribonucleosides were
      synthesized and converted chemically into corresponding 5'-O-triphosphates.
      Substrate properties of the triphosphates toward some RNA and DNA polymerases are
      reported.

PMID- 18058542
TI  - Approach to the synthesis of natural and modified oligonucleotides by the
      phosphotriester method using O-nucleophilic intramolecular catalysis.
AB  - An approach to the solid phase synthesis of natural and modified oligonucleotides
      using phosphotriester technique has been developed. Particularly, this method
      allows the synthesis of ribo- and deoxyribo-oligonucleotides containing various
      2'-modified mononucleotides as well as stereodefined nucleotide phosphorothioate
      analogues.

PMID- 18058543
TI  - Glycosylation reaction via a mild and efficient one-pot reaction using doped
      natural phosphate with iodine as catalyst.
AB  - Several alpha/beta-D-ribonucleosides were synthesized in good yields under mild
      conditions by N-glycosylations of acetyl 2,3,5-tri-O-benzoyl-beta-D-ribofuranose
      with silylated nucleobases in acetonitrile using NP doped with iodine as
      catalyst.

PMID- 18058544
TI  - The synthesis and properties of tricyclic analogues of S6-methylthioguanine and
      O6-methylguanine.
AB  - The syntheses of novel tricyclic pyrrolo[2,3-d]pyrimidine analogues of O(6)
      methylguanine and S(6)-methylthioguanine are described. The crystal structures
      and pK(a) values of these analogues are reported. In a standard substrate assay
      with the human repair protein O(6)-methylguanine-DNA methyltransferase (MGMT)
      only the oxygen-containing analogue displayed activity.

PMID- 18058545
TI  - A glutaric acid ester as carrier system for sustained delivery of lamuvidine
      (3TC) dimers.
AB  - We report the synthesis of homo and heterodimers of 3TC conjugates. All new
      dimers were screened for their ability to inhibit HIV-1 in MT4 cell line and were
      compared to AZT alone and showed marked antiviral activity.

PMID- 18058546
TI  - Synthesis and anti-HSV activity of new N1-acyclic C4 and C6-disubstituted
      pyrazolo[3,4-d]pyrimidine nucleosides.
AB  - Several N(1)-(2-hydroxyethoxy)methyl, (4-hydroxybutyl) and (2,3-dihydroxy-1
      propoxy)methyl-C(4),C(6)-disubstituted-1H-pyrozolo[3,4-d]pyrimidines were
      synthesized. Some of them were evaluated against herpes simplex virus 1 and 2
      replications in E(6)SM cells.

PMID- 18058547
TI  - Stereospecific synthesis of (-)-neplanocin F.
AB  - The stereospecific synthesis of (-)-neplanocin F was achieved in 15 steps from
      2,3-O-isopropylidene-D-1,4-ribonolactone. The synthetic methodology can give an
      access through appropriate modifications to new series of carbanucleosides.

PMID- 18058548
TI  - Effect of cationic comb-type copolymer on quadruplex folding of human telomeric
      DNA.
AB  - Cationic comb-type copolymer (CCC) consisting of a polycationic backbone and
      abundant graft water-soluble chains exhibited considerable stabilization effect
      on DNA hybrids, such as double- and triple-stranded DNAs. Here, we describe the
      effect of CCC on antiparallel G-quadruplex folding of human telomeric DNA,
      d(GGGTTA)(n) in the presence of sodium ions. CCC did not significantly alter the
      circular dichroism (CD) spectra of d((GGGTTA)(3)GGG) and d((GGGTTA)(7)GGG)
      indicating that the CCC did not influence the antiparallel folding of the
      telomeric repeats. Hence, the ionic interaction of CCC with the DNA sequence did
      not interfere with specific interaction of the DNA with sodium ions to form G
      quartets. Interestingly, CCC did not change the melting temperature of the
      d((GGGTTA)(3)GGG) suggesting negligible stabilizing effect of CCC on the
      antiparallel quadruplex structure.

PMID- 18058549
TI  - Molecular modelling studies on the binding of some protides to the putative human
      phosphoramidase Hint1.
AB  - The aim of the present work is to investigate through molecular modelling the
      possible role of the human enzyme Hint1 in the final P-N bond cleavage of
      phosphoramidate ProTides, which would lead to the intracellular delivery of
      unmasked nucleoside analogue monophosphates. Herein, we report our preliminary
      analysis based on docking studies of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU)
      related aminoacyl phosphates with Hint1 and the effect of the amino acid moiety
      on the enzyme-substrate binding affinity.

PMID- 18058550
TI  - Revisited 3'-deoxy-3'-C-methyl-beta-D-ribonucleoside series.
AB  - The synthesis of some 3'-deoxy-3'-C-methylnucleoside analogues bearing naturally
      occuring nucleic acid bases was achieved from the preparation of a suitable
      peracylated 3-deoxy-3-C-methyl sugar using a stereoselective pathway. In
      addition, examples of chemical modifications at the 2' position are presented.

PMID- 18058551
TI  - Effect of rubidium and cesium ions on the dimeric quaduplex formed by the
      Oxytricha nova telomeric repeat oligonucleotide d(GGGGTTTTGGGG).
AB  - The DNA sequence d(GGGGTTTTGGGG) consists of 1.5 units of the repeat in telomeres
      of Oxytricha nova. It has been shown by NMR and x-ray crystallographic analysis
      that it is capable to form a dimeric quadruplex structure and that a variety of
      cations, namely K(+), Na(+), and NH(4)(+), are able to interact with this complex
      with different affinity, leading to complexes characterized by different local
      conformations. Thus, in order to improve the knowledge of this kind of molecule,
      and in particular to provide further insight into the role of monovalent cations
      in the G-quadruplex folding and conformation, we have investigated by (1)H-NMR
      the effect of the addition of Rb(+) and Cs(+) to the quadruplex formed by the
      oligonucleotide d(GGGGTTTTGGGG).

PMID- 18058552
TI  - Structural insight into the hTERT intron 6 sequence d(GGGGTGAAAGGGG) from 1H-NMR
      study.
AB  - The interest in DNA quadruplex structures has been fueled by the recognition that
      telomeres, the 3' single stranded guanine-rich overhangs found at the termini of
      chromosomes, are likely to form G-tetrads type structures important in cell
      senescence and cancer. In addition to their presence in telomeres, where they may
      play a role in maintaining the stability and integrity of chromosomes, guanine
      rich regions are found in other region of the genome, amongst these is intron 6
      of hTERT a gene codifying for the enzyme telomerase. Interestingly, the formation
      of G-quadruplexes in this region is involved in the down-regulation of telomerase
      activity caused by an alteration of the hTERT splicing pattern. Therefore, we
      have analyzed several sequences of that intron by (1)H-NMR and CD spectroscopy,
      and we have found that the sequence d(GGGGTGAAAGGGG) is able to fold in a single
      well-defined antiparallel quadruplex structure consisting of four G-tetrads,
      possessing a twofold symmetry, and containing four Gs in a syn glycosidic
      conformation.

PMID- 18058553
TI  - Molecular modelling studies of four stranded quadruplexes containing a 3'-3' or
      5'-5' inversion of polarity site.
AB  - Recently we reported a preliminary study on the structure of two novel quadruplex
      structures, Q33 and Q55, formed by the oligodeoxynucleotides (5)'TGG(3)'
      (3)'GGT(5)' and (3)'TGG(5)'-(5)'GGT(3)', respectively. Here we report their
      solution structures at the atomic level. The obtained structures reveal that Q55
      and Q33 possess a different stacking among G-quartets and different twist angle
      (and therefore different helical winding) at the inversion of polarity level.

PMID- 18058554
TI  - A mini-library of TBA analogues containing 3'-3' and 5'-5' inversion of polarity
      sites.
AB  - Several researches have been devoted to structure-activity relationship and to
      post-SELEX modifications of the thrombin binding aptamer (TBA), one of the first
      aptamers discovered by the SELEX methodology. However, no studies on TBA dealing
      with the effects of introduction of inversion of polarity sites have been
      reported yet. In this frame, we have undertaken the synthesis and the study of a
      mini-library composed of several TBA analogues containing a 3'-3' or a 5'-5'
      inversion of polarity site at different positions into the sequence.
      Particularly, in this article, we present preliminary results about their
      structural and biological properties.

PMID- 18058555
TI  - Effect of the introduction of an A-residue into a quadruplex forming
      oligonucleotide containing a 5'-5' polarity of inversion site.
AB  - Preliminary NMR studies on structure formed by sequence 3'-TGA-5'-5'-GGT-3' are
      described. We proposed the formation of a tetramolecular quadruplex in which
      strands are equivalent to each other and three G-tetrads are present. The
      possibility of the occurrence of an A-tetrad also is discussed.

PMID- 18058556
TI  - A topological classification of G-quadruplex structures.
AB  - A topological classification of most quadruplex structures is proposed, based on
      two main characteristics: 1) the relative orientation of the strands and 2) the
      nature of the loops connecting the strands.

PMID- 18058557
TI  - Synthesis and primary evaluation of novel HIV-1 inhibitors.
AB  - The overcoming of antiviral drug resistance is an important challenge in the
      treatment of HIV-1 infection. According to the theory of viral error catastrophe,
      slightly increasing the mutation rate could exceed the error threshold for
      viability of a viral population and kill it. Investigation of this mechanism
      could lead to the discovery of new antiviral agents capable of bypassing viral
      resistance. To this aim, we designed several modified nucleosides. We describe
      here the synthesis and partial evaluation of 8-amido-2'-deoxyadenosine. The
      supplementary amide group on the base should allow base-pairing with several
      natural nucleosides, thus creating supplementary mutations that would kill the
      virus.

PMID- 18058558
TI  - The support-on-support concept for in-situ oligonucleotide synthesis on
      nanoparticles.
AB  - Oligonucleotide-loaded nanoparticles, which are of interest for biomedical
      application, up to now, could not be prepared by in-situ synthesis, due to
      difficulty of handling in automated synthesizers. To overcome this problem, we
      have introduced the "support-on-support" concept. It is based on the reversible
      anchoring of nanoparticles to the surface of microparticles. These composite
      beads easily can be used for automated synthesis, being released after completion
      of chain elongations. As examples, dextran-coated magnetite nanoparticles were
      attached to polystyrene microparticles through (1) a gelatine or (2) a silica
      layer. Release involved dissolution of the bonding layer by (1) proteases or (2)
      alkali.

PMID- 18058559
TI  - Thermodynamic studies on PNA and PNA/DNA dendrimer formation.
AB  - In this work we report a kinetic and thermodynamic study relative to the
      formation of gel systems based on PNA and PNA/DNA dendrimers, useful for drug
      delivery or diagnostic applications. We realized two kinds of systems: a PNA
      based monomolecular system formed by an autoassembling PNA tridendron (A) and a
      PNA/DNA bimolecular system based on a PNA tridendron with a mixed sequence and a
      DNA crosslinker (B). Both systems have the ability to form a three-dimensional
      network by means of specific W-C base pairing.

PMID- 18058560
TI  - Photochemically induced RNA and DNA abasic sites.
AB  - Two phosphoramidite building blocks were synthesized that can easily be
      deprotected by UV light to reveal natural abasic sites in oligoribonucleotides as
      well as in oligodeoxyribonucleotides. Another building block which releases a 2'
      O-methylated abasic site upon UV radiation is also described.

PMID- 18058561
TI  - Cyclopentane-nucleobase coupling in the synthesis of carbocyclic L-nucleosides:
      is a SN2-reaction an alternative to the Mitsunobu-reaction?
AB  - Several carbocyclic L-nucleosides have been synthesized by coupling a
      cyclopentane-system with heterocycles according to a modified Mitsunobu-protocol.
      This reaction gave two regioisomers, the N1-alkylated product and an unwanted
      O(2)-product. A simple S(N)2-reaction has been investigated as an alternative for
      such couplings.

PMID- 18058562
TI  - Synthesis and properties of oligonucleotides containing a 7-membered (oxepane)
      sugar ring.
AB  - Herein we describe the synthesis of novel 7-membered ring (oxepane) thymine and
      adenine nucleosides (oT and oA) and their corresponding 5'-O-phosphoramidite
      derivatives. Two homopolymeric sequences (oT(15) and oA(15)) were prepared via
      conventional solid-phase synthesis. The mutually complementary strands had the
      ability to form a duplex (oT(15):oA(15)) exhibiting a transition temperature of
      12 degrees C. The oxepane oligonucleotides were also found to associate with
      their respective complementary RNA strands thus forming oT(15):rA(15) (13 degrees
      C) and oA(15):rU(15) (12 degrees C) hybrids. The corresponding native duplexes,
      namely dT(15):dA(15), dT(15):rA(15) and dA(15):rU(15) had melting temperatures of
      37 degrees C, 32 degrees C and 16 degrees C, respectively. The CD spectrum of
      oT(15):rA(15) closely resembled that of the native dT(15):rA(15) hybrid and, in
      fact, both were found to be substrates for E. Coli RNase H. Thus the oxepane
      nucleic acids reported here are one of only a handful of DNA mimics capable of
      activating RNase H when bound to RNA.

PMID- 18058563
TI  - DNA polymerase recognition of 2'-deoxy-2'-fluoroarabinonucleoside 5'
      triphosphates (2'F-araNTPs).
AB  - We examined the ability of 2'-deoxy-2'-fluroarabinonucleoside 5'-triphosphates
      (2'F-araNTPs) to serve as substrates of various DNA polymerases. In addition, we
      also examined the ability of these polymerases to accept DNA-FANA (2'-deoxy-2'
      fluoroarabinonucleic acids) chimeras as template strands while synthesizing a DNA
      or FANA-DNA complementary strand. We provide preliminary data demonstrating that
      2'F-araNTPs are indeed substrates of several DNA polymerases, and that FANA-DNA
      chimeric templates are generally well recognized by these polymerase enzymes.

PMID- 18058564
TI  - Introduction of chirality into PNA by replacement of the achiral methylene
      carbonyl linkage to the nucleobase.
AB  - A novel approach to the introduction of chirality into peptide nucleic acid (PNA)
      by replacement of the methylene carbonyl linker by an alpha-amino acid derived
      moiety is described. A monomer compatible with Fmoc-based oligomerization
      chemistry possessing an L-serine derived linker has been synthesized and
      incorporated into PNA oligomers. A single, central substitution in a hexathymine
      PNA strongly destabilized triple helix formation whereas a central substitution
      in a mixed sequence is much better tolerated. We have investigated the influence
      of this substitution on the selectivity for strand composition (DNA versus RNA
      complement) and strand orientation (antiparallel versus parallel) in the context
      of duplex formation. A PNA 11-mer with a single substitution demonstrates a
      preference for an antiparallel RNA complement, as judged by thermal denaturation
      analysis of the complexes.

PMID- 18058565
TI  - Synthesis of a fluorescent PNA monomer containing 5-((9H-fluoren-2
      yl)ethynyl)uracil.
AB  - Pyrimidine nucleobases bearing 5-phenylethynyl substitution represent compact and
      intrinsically fluorescent nucleobases. Such nucleobases are capable of selective
      recognition of a complementary base and may fluorimetrically report on
      hybridization events. Our past work has demonstrated that the fluorescence of 5
      phenylethynyluracils is sensitive to substitution on the phenyl ring, however
      these are relatively weak fluorophores. We currently are pursuing the
      functionalization of the phenyl group of these modified nucleobases in order to
      further improve their fluorescence response, increase their aqueous solubility
      and stabilize hybrids formed with complementary nucleic acids. As an example of
      this work, we have synthesized the 5-((9H-fluoren-2-yl)ethynyl)uracil PNA monomer
      that will be incorporated into oligomers using Fmoc-based chemistry. Initial
      evaluation of the fluorescence of the 5-((9H-fluoren-2-yl)ethynyl)uracil
      derivative shows that the fluorescence intensity is approximately 50 times
      greater than a similar 5-phenylethynyluracil derivative when under identical
      conditions.

PMID- 18058566
TI  - Synthesis of modified nucleosides for incorporation of formyletheno and
      carboxyetheno adducts of adenine nucleosides into oligonucleotides.
AB  - Three protected derivatives of 1,N(6)-ethenoadenine nucleosides, viz. 3-[5-O
      (4,4'-dimethoxytrityl) of 7-formyl-(1) and 7-(1,2-diacetyloxypropyl)-2'
      deoxyadenosine (2), and 3-[5-O-(4,4'-dimethoxytrityl)-2-O-(tert
      butyldimethylsilyl)-7-(ethoxycarbonyl)adenosine (3), expected to allow
      introduction of formyletheno and carboxyethenoadenine adducts into
      oligonucleotides by the conventional phosphoramidite chemistry, have been
      synthesized.

PMID- 18058567
TI  - In vitro incorporation of LNA nucleotides.
AB  - An LNA modified nucleoside triphosphate 1 was synthesized in order to investigate
      its potential to act as substrate for DNA strand synthesis by polymerases. Primer
      extension assays for the incorporation experiments revealed that Phusion High
      Fidelity DNA polymerase is an efficient enzyme for incorporation of the LNA
      nucleotide and for extending strand to full length. It was also observed that pfu
      DNA polymerase could incorporate the LNA nucleotide but it failed to extend the
      strand to a full length product.

PMID- 18058568
TI  - Detecting DNA: getting and begetting cancer.

PMID- 18058569
TI  - Biological therapy of breast cancer: recent clinical applications.
AB  - Advances have been made in breast cancer therapy, in both the adjuvant and
      metastatic settings. For example, in the adjuvant setting, genomic studies of
      breast cancer tissues have identified women with estrogen receptor-positive
      tumors who might not require chemotherapy, leading to the development of a
      diagnostic tool. There have also been significant developments with anticancer
      agents that target tumor cell surface receptors, such as HER2/neu, and those
      involved in angiogenesis and kinase-dependent pathways. New areas of research
      focus on the concept of breast cancer stem cells as well as the prognostic
      importance of bone marrow micrometastases in early-stage breast cancer. This
      review summarizes these advances in breast cancer clinical research.

PMID- 18058570
TI  - Monoclonal antibodies in clinical hematology and oncology.
AB  - The application of highly specific mAbs with minimal side effects in cancer
      therapy was, for a long time, a major goal for many clinical oncologists. Since
      their arrival in the clinical setting, mAbs have come to represent a standard
      therapy for some tumors, and have proven to be an important extension to the
      treatment of a broad spectrum of malignancies. The future development of mAbs for
      targeting alone (ie, for labeling of tumors) is insufficient for obtaining a
      suitable clinical response, and adequate clinical success can only be achieved by
      arming mAbs and targeting them to functionally significant tumor antigens such as
      tumor growth-related receptors. This review provides an overview of the
      functional characteristics of mAbs, together with some important examples of
      their clinical application. While mAbs may not be the 'magic bullets' that many
      researchers had hoped for, they are nevertheless becoming an indispensable pillar
      of tumor therapy.

PMID- 18058571
TI  - Targeting CD4+CD25+FoxP3+ regulatory T-cells for the augmentation of cancer
      immunotherapy.
AB  - CD4+CD25+FoxP3+ T-regulatory (Treg) cells are vital to the maintenance of
      peripheral self tolerance and are implicated in tolerance to foreign antigens.
      Increasing evidence shows that Treg cells may also play an important role in
      immune evasion mechanisms employed by cancer. Treg cells are actively recruited
      and induced by tumors to block innate and adaptive immune priming, effector
      function and memory response, which can inhibit the efficacy of therapeutic
      cancer vaccines. As such, modulation of Treg cell function in cancer has been
      studied using various approaches, with encouraging preclinical and clinical
      findings. However, controlled and effective modulation of Treg cell function for
      cancer therapeutics will be contingent on a better understanding of the molecular
      basis of Treg cell interaction with tumor cells and ensuing immunosuppressive
      mechanisms.

PMID- 18058572
TI  - Small-molecule and antibody approaches to molecular chemotherapy of primary brain
      tumors.
AB  - High-grade primary brain tumors remain refractory to conventional treatment
      approaches, including radiotherapy and cytotoxic chemotherapy. Molecular neuro
      oncology has now begun to clarify the transformed phenotype of these malignant
      tumors and identify oncogenic pathways that might be amenable to small-molecule
      and antibody 'targeted' therapy. Growth factor signaling pathways are often
      upregulated in these tumors and contribute to oncogenesis through autocrine and
      paracrine mechanisms. Excessive growth factor receptor stimulation can also lead
      to overactivity of the downstream Ras signaling pathway. Other internal signal
      transduction pathways that may become dysregulated during transformation include
      Raf, MEK, PI3K, Akt (protein kinase B), and mTOR (mammalian target of rapamycin).
      In addition, overactivity of VEGF and other effectors leads to neoplastic
      angiogenesis. 'Targeted' therapy against the growth factor signaling and Ras
      pathways include tyrosine kinase inhibitors (eg, imatinib and erlotinib) and
      farnesyltransferase inhibitors (eg, tipifarnib). Molecular therapeutic small
      molecules specific to Raf, PI3K, and mTOR include sorafenib, LY-294002, and
      temsirolimus, respectively. 'Targeted' anti-angiogenesis approaches include mAbs
      to VEGF (eg, bevacizumab) and VEGF receptor tyrosine kinase inhibitors (eg,
      vatalanib and sunitinib). Further development of 'targeted' therapies designed to
      modulate the activity of these pathways, and evaluation of these new agents in
      clinical trials, will be needed to improve survival and quality-of-life for
      patients with malignant brain tumors.

PMID- 18058573
TI  - Experimental therapeutics: targeting the redox Achilles heel of cancer.
AB  - Reactive oxygen species (ROS) have recently emerged as promising targets for
      anticancer drug discovery. Constitutively elevated levels of cellular oxidative
      stress and dependence on mitogenic and anti-apoptotic ROS signaling represent a
      specific vulnerability of malignant cells that can be selectively targeted by
      novel pro- and antioxidant redox chemotherapeutics. This review discusses small
      molecule anticancer redox drugs currently in various phases of preclinical and
      clinical development that are characterized by their unique mechanism of action,
      including small-molecule superoxide dismutase and catalase mimetics,
      bioreductively activated pro-oxidant redox catalysts, metal-based pro-oxidants,
      hypoxia-selective free radical precursors, and specific antagonists of the cancer
      cell antioxidant glutathione or thioredoxin redox systems. Based on ongoing redox
      biomarker discovery and validation, future redox phenotyping and genotyping may
      guide the selection of novel redox chemotherapeutics that efficiently target the
      redox Achilles heel of the individual tumor.

PMID- 18058575
TI  - Clinical poly(ADP-ribose) polymerase inhibitors for the treatment of cancer.
AB  - Poly(ADP-ribose) polymerase (PARP) is believed to play a critical role in the
      detection of DNA damage and initiation of DNA repair. Although inhibition of PARP
      has received increasing attention for therapeutic application in a wide variety
      of acute and chronic diseases, most of the current clinical data surrounding PARP
      inhibition is in the field of oncology. At least eight different PARP inhibitors
      have been, or are expected to be evaluated in the clinical oncology setting in
      2007 and 2008. This review summarizes the most recently presented or published
      data on these therapeutic molecules, and discusses how these drugs may continue
      to be developed in the future.

PMID- 18058574
TI  - Preventive and therapeutic HPV vaccines.
AB  - Cervical cancer is the second leading cause of cancer deaths in women worldwide
      and HPV infection is responsible for the development of this cancer. Effective
      vaccination against HPV represents an opportunity for the control of cervical
      cancer. The newly licensed preventive HPV vaccine in the US, Gardasil, has both a
      good safety profile and clinical efficacy against the HPV genotypes from which it
      was derived. However, this vaccine can only protect against up to 70 to 80% of
      cervical cancer and also lacks therapeutic efficacy against established HPV
      infection and HPV-associated lesions. Thus, the future of HPV vaccination needs
      to focus on the development of a new generation of preventive and therapeutic
      vaccines that are capable of protecting against most cervical cancers.

PMID- 18058576
TI  - Eribulin, a simplified ketone analog of the tubulin inhibitor halichondrin B, for
      the potential treatment of cancer.
AB  - Eisai Co Ltd is developing eribulin, a simplified synthetic macrocyclic ketone
      analog of the tubulin inhibitor halichondrin B, for the potential treatment of
      cancer. Phase III trials are underway in the US and Europe for patients with
      breast cancer. Eribulin is currently in phase II trials for NSCLC and soft tissue
      sarcoma, and pancreatic, prostate, ovarian, fallopian tube, peritoneal and head
      and neck cancer, and phase I/II trials for urothelial cancers.

PMID- 18058577
TI  - MORAb-003, a fully humanized monoclonal antibody against the folate receptor
      alpha, for the potential treatment of epithelial ovarian cancer.
AB  - Morphotek Inc is developing MORAb-003, a humanized monoclonal antibody directed
      against folate receptor alpha, for the potential treatment of ovarian cancer.
      Phase II clinical trialsof MORAb-003, either alone or in combination with
      platinum/taxane chemotherapy, are underway in ovarian cancer patients
      experiencing their first disease recurrence.

PMID- 18058578
TI  - Comparison of primary balloon angioplasty with bailout stenting strategy to
      primary coronary stenting strategy in the treatment of patients with ST-segment
      elevation myocardial infarction (STEMI).
AB  - BACKGROUND: In recent years significant progress has been made in invasive
      treatment of patients with acute myocardial infarction (AMI). Primary coronary
      stenting is currently a routine strategy which replaced primary balloon
      angioplasty with bailout stenting preferred in the past. Studies comparing these
      two strategies of stenting in AMI are scarce. AIM: To compare the immediate and
      long-term outcomes after primary angioplasty strategy and bailout stenting versus
      primary stent placement strategy in patients with AMI. METHODS: We analysed data
      from a single-centre registry of consecutive patients with ST segment elevation
      myocardial infarction admitted between January 1998 and October 2003. In our
      centre in years 1998-2000 stenting was used only after failed or suboptimal
      balloon angioplasty. Starting from year 2001 we used routine primary stenting
      strategy. We compared these two angioplasty strategies applied in different time
      intervals with regard to in-hospital outcome and long-term mortality. Patients
      with cardiogenic shock at admission were excluded. RESULTS: Out of a total of
      1602 patients treated invasively for AMI (cardiogenic shock excluded) 479
      underwent primary balloon angioplasty strategy with bailout stenting - group 1
      (years 1998-2000) and 1123 were treated with primary stenting strategy - group 2
      (years 2001-2003). In group 1 bailout stenting occurred in 34.4% of patients
      whereas in group 2 stents were implanted in 83% of patients. Patients in the
      balloon angioplasty group were younger, had shorter time from the onset of
      symptom to hospital arrival and more frequently underwent rescue coronary
      intervention after failed thrombolysis. In-hospital mortality was 2.9 vs. 2.4% in
      groups 1 and 2, respectively (p=NS). Twenty-four month mortality rate was 9.8% in
      group 1 and 10.06% in group 2 (p=NS). CONCLUSIONS: 1. Effectiveness of coronary
      angioplasty is high and comparable in both groups. 2. In-hospital and long-term
      mortality and procedure-related complication rate are all low and comparable with
      both stenting strategies. 3. Independent factors increasing long-term mortality
      include: culprit vessel reocclusion, multivessel coronary disease, older age and
      hypertension. 4. Patients with complete patency of culprit vessel restored and
      with higher left ventricular ejection fraction presented lower 2-year mortality
      rate. 5. Bailout stenting did not increase 2-year mortality.

PMID- 18058579
TI  - Mortality in patients with heart failure treated with cardiac resynchronisation
      therapy. A long-term multi-centre follow-up study.
AB  - BACKGROUND: Benefits of cardiac resynchronisation therapy (CRT) for survival in
      selected congestive heart failure (CHF) patients have been acknowledged by the
      2005 ESC guidelines. AIM: To analyse mortality in CRT pacing only (CRT-P)
      patients during at least one-year follow-up. METHODS: This was a prospective,
      multi-site, at least one-year observational study on mortality and mode of death
      in patients who received CRT-P due to commonly accepted indications. One-year
      follow-up data (or earlier death) were available for 105 patients (19 females, 86
      males) aged 60.6+/-9.8 years (35-78). Baseline NYHA class was 3.2+/-0.4 (3-4).
      Coronary artery disease (CAD) was the underlying aetiology of CHF in 57 (54%)
      patients and 48 (46%) patients had CHF due to non-coronary factors. RESULTS: Mean
      follow-up duration was 730 days (360-1780), median 625. There were 21 (20%)
      deaths: 5 (24%) sudden cardiac deaths (SCD), 13 (62%) deaths due to heart failure
      (HFD) and 3 (14%) other deaths. Thirteen (62%) patients died within the first
      year of observation. All SCD occurred in this period. Mean time to death was
      303+/-277 days (19-960) to HFD - 339+/-313 days (19-960) and to SCD - 208+/-127
      days (31-343). There were no significant differences between survivors and non
      survivors with respect to left ventricular ejection fraction (LVEF) (25+/-10 vs.
      20+/-8%), 6-minute walk test (6 min WT) (276+/-166 vs. 285+/-163 m) and LV
      diastolic diameter (LVEDD) (71+/-9 vs. 78+/-10 mm) (all NS). The SCD and HFD
      patients had similar age (62.0+/-5.4 vs. 56.6+/-13.2 years), gender (80 vs. 83%
      males), NYHA class (3.1+/-0.2 vs. 3.5+/-0.3), LVEF (22+/-9 vs. 17+/-5%), LVEDD
      (86+/-10 vs. 79+/-9 mm), 6 min WT (270+/-142 vs. 292+/-188 m) (NS). In 4 patients
      from the SCD group CHF was of non-coronary aetiology and only in 1 patient from
      the HFD group (p=0.003). The values of LVEF, LVEDD and NYHA class in HFD patients
      who died during the first year after implantation, compared with those who died
      later, were similar. CONCLUSIONS: Sudden cardiac death probability in the studied
      CRT-P population was the highest during the first year after implantation.
      Afterwards, the risk of HFD started to increase. Thus, in all patients eligible
      for CRT prophylactic defibrillation function should be considered.

PMID- 18058580
TI  - Impact of the time to reperfusion on early outcomes in patients with acute
      myocardial infarction undergoing primary angioplasty.
AB  - BACKGROUND: The ACC/AHA guidelines for management of patients with ST-elevation
      myocardial infarction (STEMI) have recommended primary PCI (pPCI) as the
      preferred reperfusion therapy, when it can be performed in a timely fashion,
      within 90-110 min from the first contact with medical personnel. The impact of
      treatment delays on outcomes in patients undergoing pPCI has been controversial.
      AIM: To evaluate the impact of time delays on in-hospital mortality and on the
      frequency of cardiac events during 30 days after STEMI. METHODS: 1723 patients
      were stratified on the basis of their time delays: from symptom onset until
      balloon inflation. The patients were divided into 4 groups: group 1 (311
      patients) - time from symptom onset <90 min; group 2 (731 patients) - time delays
      of 90-180 min; group 3 (535 patients) - time delays of 180-360 min, and group 4
      (146 patients) - time from symptom onset >360 min. RESULTS: The median time delay
      was 268.5+/-206 min, the median door to balloon time was 36.12+/-11.2 min. The
      patients with longer time delays (group 4) were older, more often were women, and
      had a higher frequency of diabetes, anterior MI and Killip class 4. During
      hospitalisation, 70 (4.1%) patients died. In-hospital mortality was significantly
      higher in group 4 (13.6%) than in other groups. Complications of STEMI such as
      cardiogenic shock considerably influenced mortality (45.6%). During a 30-day
      follow- -up, the patients with cardiogenic shock and the elderly had an increased
      risk of cardiac events. Also, time delays >360 min and failed pPTCA were
      independent adverse risk factors in multivariate regression analysis. CONCLUSION:
      Delays in time to pPCI have an impact on outcomes, especially in those treated >6
      hours from the onset of symptoms.

PMID- 18058581
TI  - Factors affecting the progression of atherosclerosis in the coronary arteries.
AB  - BACKGROUND: The induction and progression of atherosclerotic changes is complex
      and influenced by many factors. The most important are enhanced concentration of
      LDL cholesterol, enlarged production of free radicals, the inflammatory reaction,
      endothelial damage, decreased concentration of HDL and increased prothrombotic
      activity. AIM: To define the factors influencing the atherosclerotic process in
      the coronary arteries of patients with coronary disease in serial coronary
      examinations. METHODS: In the 2nd Department of Cardiology in the Medical
      University of Lodz, 8989 coronary angiography studies were performed between
      January 1999 and May 2004. The second intervention in the earlier studied
      patients was made because of clinical indications. The investigation included 177
      consecutive patients (128 men and 49 women) in whom the coronary angiography was
      executed at least twice. RESULTS: A significantly larger degree of
      atherosclerotic process occurred in the group of patients younger than the
      average age of the studied group (p=0.004), in those with a family history of
      circulatory diseases (p=0.02), as well as in patients with numerous risk factors
      of coronary disease (p=0.01). In the well-fitted model of the prediction of
      progression of vascular changes, according to the Gensini Score in individual
      time (p <0.02), two independent parameters were identified - gender (p=0.04) and
      statin therapy (p=0.03). The odds ratio with 95% confidence interval in males was
      2.1 (1.1-5.2), and for the use of statin - 0.48 (0.21-0.91). CONCLUSIONS:
      Significant progression of atherosclerotic changes in the coronary vessels was
      confirmed in the studied population. In the group of men faster progression of
      atherosclerotic changes, in particular of lesions in the proximal parts of the
      coronary arteries, was confirmed, whereas therapy with statins significantly
      slowed down this process in all studied sections of the coronary arteries,
      especially in their distal parts.

PMID- 18058582
TI  - Different reactivity of the proximal and distal segments of the radial artery to
      vasoconstrictors in patients undergoing coronary artery bypass grafting.
AB  - BACKGROUND: Complete arterial revascularisation using the radial artery (RA) is
      an attractive alternative to venous graft implantation for the coronary artery
      bypass grafting (CABG). In spite of the favourable long-term results of this
      approach, the sensitivity of RA to vasoconstriction and spasm is still limiting
      its use. It has been suggested that vasospastic properties of the artery may
      differ depending on the location (proximal or distal). AIM: To compare the
      vasoreactive properties of proximal and distal sections of RA grafts. METHODS:
      Proximal and distal segments of RA were obtained from 27 patients undergoing CABG
      and isometric recordings of changes in smooth muscle force were performed mounted
      in the organ bath. Responses to cumulatively increasing concentrations of
      phenylephrine (PE), angiotensin II (AT-II), prostaglandin F2 (PGF2) and
      endothelin-3 (ET-3) were evaluated. RESULTS: Both proximal and distal segments of
      RA constricted in response to KCl, PE, AT-II, PGF2 and ET-3. Proximal segments
      demonstrate significantly greater spastic response to KCl, as well as to receptor
      mediated agonists PE and more importantly vasoactive peptide AT-II. These
      differences remained statistically significant after correcting for vessel size
      and weight. In contrast, reactivity of both segments of RA to increasing
      cumulative doses of PGF2 and ET-3 was similar. CONCLUSION: Proximal segments of
      the radial artery are more susceptible to vasoconstriction induced by PE and AT
      II, which should be taken into consideration in the clinical setting of CABG
      surgery. Increased muscle content in this segment does not fully explain this
      difference, which may result from varying receptor density and properties.

PMID- 18058583
TI  - Usefulness of ambulatory ECG in the diagnosis of sleep-related breathing
      disorders.
AB  - BACKGROUND: Sleep-related breathing disorders (SRBD) are the additional factor
      related to poor prognosis in patients with cardiovascular disorders. The
      apnoea/hypopnoea index (AHI), describing the number of apnoea and hypopnoea
      episodes per one hour of sleep, has been used as a marker of severity of the
      disorder. The disease is present in 4% of men and 2% of women above 40 years of
      age. However, SRBD are diagnosed in less than 3% of patients with this syndrome
      due to lack of awareness of the disease among health care practitioners and
      patients. Polysomnography (PSG) has been used as a golden standard for detecting
      SRBD, however this test is available only in selected centres. Therefore, a
      simple, fast and inexpensive test for screening for SRBD is necessary.
      Respiratory activity influences the amplitude of ECG signal whereas heart rate
      variability (HRV) depicts the activity of the autonomic nervous system. These
      associations have been used to develop a new method for detection of SRBD
      involving analysis of HRV and morphology of ECG signal in ECG monitoring. AIM:
      Assessment of accuracy of SRBD detection using estimated AHI (Est.AHI),
      calculated from Holter ECG recordings. METHODS: In a study group consisting of 74
      patients tested for SRBD, simultaneous PSG and 24-hour ECG monitoring were
      performed. Following PSG, AHI for each patient was calculated. According to the
      AHI values patients were classified as SRBD patients (AHI >15), non-SRBD patients
      (AHI <5), whereas 12 individuals had borderline SRBD (5< or = AHI < or =15). Age,
      prevalence of concomitant disorders and treatment were similar in all groups. In
      all individuals the Est.AHI value was calculated based on ECG recording.
      Considering the AHI value as a reference parameter discriminating SDB and non
      SRBD patients, the number of false positive and false negative results for
      detecting SDB with the Est.AHI was calculated. Moreover, the SRBD detection
      accuracy using the Est.AHI calculation was evaluated by the receiver-operator
      characteristic (ROC) curves which were used to calculate area under curve (AUC),
      sensitivity, specificity, as well as positive (PPV) and negative (NPV) predictive
      values for optimal cut-off value. RESULTS: According to Est.AHI, 50 (68%)
      patients were correctly diagnosed. The ROC analysis showed high accuracy of SRBD
      detection using Est.AHI: AUC - 0.91 with sensitivity - 91.2%, specificity -
      87.5%, PPV - 88.6%, and NPV - 88.9%. The cut-off value of Est.AHI set at 17 was
      optimal for the differentiation between patients with or without SRBD.
      CONCLUSIONS: The Est.AHI calculated with the Lifescreen Apnea software from
      Holter ECG is an accurate, specific and sensitive method for the detection and
      classification of obstructive and mixed SRBD.

PMID- 18058584
TI  - [Cardiac resynchronisation therapy as a cause of the electrical storm].
AB  - We report a case of young patient with dilated cardiomyopathy and implanted
      cardioverter-defibrillator in which resynchronisation therapy (CRT-D) induced an
      electrical storm. One month after implantation of a cardiac resynchronisation
      pacemaker (CRT-P) the patient suffered from ventricular tachycardia with poor
      haemodynamic status and was treated by implantation of a CRT-D with a Y adaptor.
      After replacement of the CRT-D due to Y adaptor damage (new device without a Y
      adaptor) we observed an electrical storm during ventricular pacing
      (biventricular, right and left ventricular pacing respectively). Changing pacing
      mode from DDDR to AAIR resolved ventricular tachycardias in that patient.

PMID- 18058585
TI  - [Emergency hybrid surgery for ruptured aortic arch aneurysm--a case report].
AB  - We describe a case of 67-year-old man suffering from chronic aortic arch aneurysm
      complicated by rupture and hemorrhage to the left pleural cavity. The patient
      underwent emergency hybrid operation: extraanatomical transposition of aortic
      arch branches to ascending aorta and implantation of stentgraft into the arch
      without the extracorporeal circulation.

PMID- 18058586
TI  - [Inoperable sinus venosus atrial septal defect in a young woman with severe
      pulmonary hypertension--a case report].
AB  - Atrioventricular septal defect accounts for approximately 3% of all congenital
      cardiovascular malformations. We describe a case of a 34-year-old woman with
      inoperable sinus venosus atrial septal defect with severe pulmonary hypertension
      and symptoms of the Eisenmenger syndrome. Electrocardiography, chest radiography,
      transthoracic and transoesophageal echocardiography with and without contrast
      were performed and provided valuable information about haemodynamic consequences
      of this malformation.

PMID- 18058587
TI  - [Myocardial infarction in a 26-year-old patient with diabetes type 1].
AB  - A case of a 26-year-old patient with acute myocardial infarction and
      hypertension, hyperlipidaemia as well as type 1 diabetes from 18 years
      complicated by background retinopathy and nephropathy in the state of proteinuria
      is described. State of metabolic compensation of the diabetes was poor. The
      patient did not perform regular self-monitoring of glycaemia, smoked, and used
      oral contraception. Early diagnosis of vascular lesions in young persons with
      long-lasting of type 1 diabetes as well as the introduction of proper preventive
      and treatment methods may improve prognosis in these high-risk patients.

PMID- 18058588
TI  - [New therapeutic goals--new drugs in heart failure treatment].

PMID- 18058589
TI  - [Are genetic factors involved in the aetiology of aortic stenosis?].

PMID- 18058590
TI  - [Atrial infarction or ischaemia as the cause of atrial pacing failure in a
      patient with acute myocardial infarction].

PMID- 18058591
TI  - [Acute coronary syndrome or aortic stenosis?].

PMID- 18058592
TI  - [Dissection of coronary artery during primary PCI in a patient with rheumatoid
      arthritis].

PMID- 18058593
TI  - ["Benign" atrial arrhythmias exacerbated by physical activity as a cause of
      cardiomyopathy].
AB  - We describe a 39-year-old man with premature atrial contractions at rest, in whom
      tachycardia was exacerbated by exercise into long-lasting atrial tachycardia of
      150 beats/min with changeable grade of AV conduction. The feeling of irregular
      heart beating was the only symptom of arrhythmia and was well tolerated for many
      years. However, the signs of tachycardia-mediated cardiomyopathy with heart
      failure developed over several years. Successful RF ablation of focal atrial
      tachycardia using the CARTO system was performed. After 5 months of follow-up the
      patient is free from arrhythmia with a significant improvement of the HF.

PMID- 18058594
TI  - [Closure of patent foramen ovale in patients with cryptogenic stroke].

PMID- 18058595
TI  - Effect of hydrotherapy on recovery from fatigue.
AB  - The present study investigated the effects of three hydrotherapy interventions on
      next day performance recovery following strenuous training. Twelve cyclists
      completed four experimental trials differing only in 14-min recovery
      intervention: cold water immersion (CWI), hot water immersion (HWI), contrast
      water therapy (CWT), or passive recovery (PAS). Each trial comprised five
      consecutive exercise days of 105-min duration, including 66 maximal effort
      sprints. Additionally, subjects performed a total of 9-min sustained effort (time
      trial - TT). After completing each exercise session, athletes performed one of
      four recovery interventions (randomly assigned to each trial). Performance
      (average power), core temperature, heart rate (HR), and rating of perceived
      exertion (RPE) were recorded throughout each session. Sprint (0.1 - 2.2 %) and TT
      (0.0 - 1.7 %) performance were enhanced across the five-day trial following CWI
      and CWT, when compared to HWI and PAS. Additionally, differences in rectal
      temperature were observed between interventions immediately and 15-min post
      recovery; however, no significant differences were observed in HR or RPE
      regardless of day of trial/intervention. Overall, CWI and CWT appear to improve
      recovery from high-intensity cycling when compared to HWI and PAS, with athletes
      better able to maintain performance across a five-day period.

PMID- 18058596
TI  - Efficacy and treatment satisfaction of once-daily insulin glargine plus one or
      two oral antidiabetic agents versus continuing premixed human insulin in patients
      with type 2 diabetes previously on long-term conventional insulin therapy: the
      Switch pilot study.
AB  - BACKGROUND: Addition of the long-acting basal human insulin analogue insulin
      glargine (LANTUS) to the treatment regimen of patients with inadequate glycaemic
      control on oral antidiabetic drugs (OADs) alone has previously been evaluated as
      effective, safe and convenient. This pilot study aimed to establish whether
      insulin glargine plus OADs is effective in Type 2 diabetes patients previously
      poorly controlled on premixed insulin therapy. METHODS: In an open, controlled,
      randomized, parallel-group, single-centre, 16-week pilot study, 52 patients (age
      65.6+/-9.2 years; diabetes duration 15.3+/-7.6 years; insulin therapy duration
      4.2+/-1.7 years, body mass index 31.4+/-2.9 kg/m2) with Type 2 diabetes
      (HbA1c>or=8.0%) on premixed human insulin (75/25 or 70/30) were randomized to
      once-daily morning insulin glargine plus glimepiride (Group A; n=17), insulin
      glargine plus glimepiride and metformin (Group B; n=18) or premixed insulin
      (Group C; n=17). Glycaemic control and incidence of hypoglycaemia were evaluated.
      RESULTS: HbA1c decreased significantly from baseline in Groups A and B, but not
      in Group C; (Group A: 7.87+/-0.66%, -0.35%, p=0.013; Group B: 7.44+/-0.92%, 
      0.69%, p=0.0057; Group C: 7.83+/-1.13%, -0.25%, p=0.32). There were no between
      treatment differences at endpoint in HbA1c, fasting blood glucose, mean daily
      blood glucose or symptomatic hypoglycaemia (mean events/patient: Group A, 2.2;
      Group B, 2.3; Group C, 2.0). At endpoint, 88% of patients in Group A, 81% in
      Group B and 94% in Group C opted to continue with their assigned regimen.
      CONCLUSIONS: This pilot study is the first prospective study to show that
      switching from premixed insulin to insulin glargine plus OAD treatment resulted
      in similar glycaemic control and treatment satisfaction. The results support the
      need for prospective examination in a larger-scale clinical study in patients
      with long-standing Type 2 diabetes and sub-optimal glycaemic control previously
      using a conventional premixed insulin regimen.

PMID- 18058597
TI  - Familiality of diabetes mellitus.
AB  - The aims of this study were to estimate relative risk for type 1 and type 2
      diabetes in relatives of diabetic patients, and to test for excess relatedness
      among diabetic patients. Additionally, the difference in parental transmission of
      diabetes was investigated. This study used a unique Utah genealogical resource,
      linked to electronic medical records of the largest health provider in Utah. We
      identified 19,640 patients with a diagnosis of type 1 or type 2 diabetes.
      Relative Risks (RRs) for type 1 and type 2 diabetes were assessed for first-,
      second- and third-degree relatives of diabetic patients. The observed average
      relatedness of diabetic patients was compared to the expected relatedness using
      the Genealogical Index of Familiality (GIF). We observed significantly elevated
      RRs for type 1 diabetes in first-degree (RR=8.68; P<0.0001), second-degree
      (RR=1.93; P<0.0001) and third-degree relatives (RR=1.74; P<0.0001) of type 1
      diabetic patients. RRs for type 2 diabetes were significantly increased in first
      degree (RR=2.24; P<0.0001), second-degree (RR=1.36; P<0.0001) and third-degree
      relatives (RR=1.14; P<0.0001) of type 2 diabetic patients. Significantly
      increased RRs for type 1 diabetes were observed in the relatives of type 2
      diabetic patients, and vice versa. The GIF analysis showed significant excess
      relatedness for type 1 diabetes cases, and independently for type 2 diabetes
      cases. Offspring of diabetic fathers were at significantly higher risk for type 1
      diabetes than offspring of diabetic mothers (RR=9.73; P<0.0001 compared to
      RR=4.99; P<0.0001). No significant difference in parental transmission was
      observed for type 2 diabetes. Our results strongly support the existence of a
      genetic contribution to both type 1 and type 2 diabetes, and additionally suggest
      a relationship between both types of diabetes. Furthermore, our results suggest a
      significant difference in parental transmission of type 1 diabetes.

PMID- 18058598
TI  - Long-term effects of Terminalia chebula Retz. on hyperglycemia and associated
      hyperlipidemia, tissue glycogen content and in vitro release of insulin in
      streptozotocin induced diabetic rats.
AB  - The aqueous extract of the fruits of Terminalia chebula Retz. has been evaluated
      for its antidiabetic activity in streptozotocin (STZ) induced mild diabetic rats
      and compared with a known drug, tolbutamide. The oral effective dose (ED) of the
      extract was observed to be 200 mg/kg body weight, which produced a fall of 55.6%
      (p<0.01) in the oral glucose tolerance test. Oral administration of ED of aqueous
      extract of T.chebula (AETC) daily once for two months reduced the elevated blood
      glucose by 43.2% (p<0.01) and significantly reduced the increase in glycosylated
      hemoglobin (HbA1c) (p<0.01). The same dose also showed a marked improvement in
      controlling the elevated blood lipids as well as decreased serum insulin levels
      in contrast to the untreated diabetic animals. Hepatic and skeletal muscle
      glycogen content decreased by 75% and 62.9% respectively in diabetic controls,
      these alterations were partly prevented (34.9% and 21.17%) in AETC treated group
      when compared to the healthy controls. The in vitro studies with pancreatic
      islets showed that the insulin release was nearly two times more than that in
      untreated diabetic animals. The treatment did not have any unfavorable effect on
      other blood parameters of liver and kidney function tests. LD 50 was found to be
      above 3 g/kg bw i.e. 15 times of ED, because there were no deaths of animals even
      at this dose indicating high margin of safety. These findings suggest further
      investigations for the possible use of the aqueous extract of fruits of T.chebula
      for the treatment of diabetes.

PMID- 18058599
TI  - Impaired glucose tolerance in pancreas grafted diabetic patients is due to
      insulin secretory defects.
AB  - INTRODUCTION: Pancreas transplantation in diabetic patients can sustain insulin
      independence for years. The aim of the study was to measure the incidence of an
      impaired or diabetic glucose tolerance in patients after successful
      transplantation and analyse insulin resistance and insulin secretion. METHODS:
      174 Type 1 diabetic recipients of simultaneous pancreas/kidney (SPK) transplants
      were investigated early (three months) and 95 patients late (five years) after
      transplantation using an oral glucose tolerance test combined with an iv arginine
      load. RESULTS: Although mean fasting blood glucose and HbA1c levels were within
      the normal range, only 65% of the patients displayed a normal glucose tolerance
      (NGT), whereas 25% had an impaired (IGT) and 10% showed a diabetic glucose
      tolerance (DGT). Fasting blood glucose and HbA1c values were significantly lower
      in patients with NGT compared to graft recipients with IGT or DGT, either three
      months or five years after SPK. Indicators of insulin resistance (fasting
      insulin, HOMA-IR, Matsuda/de Fronzo Index) were elevated in all graft recipients,
      but no differences were found between groups. In contrast insulin secretion was
      significantly reduced in patients with IGT and DGT early and late after
      transplantation. SUMMARY: Insulin resistance is a common feature after pancreas
      transplantation. However, either three months or five years after SPK abnormal
      glucose tolerance was mainly due to a reduced glucose- and arginine-induced
      secretory response of insulin.

PMID- 18058600
TI  - Sustained expression of hepatocyte nuclear factor-6 leads to loss of pancreatic
      beta-cells by apoptosis.
AB  - Hepatocyte nuclear factor-6 (HNF-6) is the ONECUT-homeodomain transcription
      factor that is enriched in liver and also present in pancreas and central nervous
      system. It is expressed in the pancreatic bud at E10.5. In adult pancreas, its
      expression is restricted to the exocrine pancreas and duct cells. Since duct
      cells are thought to be precursors of endocrine cells and HNF-6 is involved in
      the regulation of the expression of HNF-4alpha and -1beta, genes that cause
      maturity onset diabetes of the young (MODY), we hypothesized that the sustained
      expression of HNF-6 would affect beta-cell function. We generated transgenic mice
      over-expressing human HNF-6 using the mouse insulin I promoter (MIP). We obtained
      one female founder in which the transgene had been incorporated into two sites;
      the chromosome (Ch) 14 and the X chromosome. The integration site of the latter
      was within centromeric heterochromatin and the transgene was inactivated. Studies
      on mice in which the transgene was integrated into Ch14 showed beta-cell specific
      defects functionally and pathologically. The insulin secretory response to
      glucose and arginine in the in situ-perfused pancreas was also significantly
      impaired in these mice. Immunohistochemical analysis revealed that the islets
      were smaller and had an abnormal architecture with an inverted ratio of alpha-
      and beta-cells resulting from beta-cell loss to 30% by 6-wk of age. The decreased
      number of beta-cells was quantified first time by fluorescent activated cell
      sorting using entire pancreata from the transgenic mice crossed with MIP-green
      fluorescent protein (GFP) mice. This severe loss of beta-cells involved
      programmed cell death.

PMID- 18058601
TI  - The rate of improvement in metabolic control in children with diabetes mellitus
      type 1 on insulin glargine depends on age.
AB  - BACKGROUND: To evaluate the changes in the glycemic profile and metabolic control
      after introducing glargine in children with DMT1 in a one-year follow up.
      METHODS: 70 children (36 boys) at the average age of 12.03+/-2.50 with the mean
      diabetes duration of 3.35+/-2.19 years were observed. Glargine was substituted
      for NPH in children treated with multiple daily injections. RESULTS: The analysis
      showed the differences in the dynamics of changes in mean glycemia based on home
      blood glucose monitoring and HbA1c between prepubertal children (Group 1) and
      teenagers (Group 2). A significant reduction in mean glycemia from baseline to 12
      months was observed at all chosen points in Group 2: fasting glycemia (125+/-27
      mg/dl vs 117+/-17 mg/dl,p<0.05), bedtime glycemia (128+/-24 mg/dl vs. 117+/-20
      mg/dl,p=0.001) and 3 a.m. glycemia (143+/-47 mg/dl vs. 90+/-25 mg/dl,p<0.001). A
      significant decrease in mean glycemia in Group 1 was observed from the beginning
      of treatment only at bedtime (0-12 months:129+/-27 mg/dl vs. 112+/-25
      mg/dl,p=0.001) and at 3 am with the delay (6-12 months:122+/-36 mg/dl vs. 90+/-22
      mg/dl,p<0.05). A significant improvement in HbA1c between baseline and 12 months
      was observed in both groups but with different dynamics of changes: 6.91+/-0.77%
      vs. 6.59+/-0.65% (p<0.05) and 7.44+/-1.26% vs. 7.18+/-1.58% (p=0.001)
      respectively in the groups. A trend towards decreasing the number of hypoglycemic
      episodes and no changes in BMI and insulin requirement were noted. CONCLUSIONS:
      Introduction of glargine provides diabetic children with a better stabilization
      of the daily glycemic profile even in the cases of baseline good metabolic
      control. The rate of reaching the target in a long-term observation depends on
      age. A slower reduction of glycemia observed in smaller subjects suggests a great
      individuality in the regimen of diabetic children.

PMID- 18058602
TI  - Effects of ghrelin, corticotrophin-releasing hormone, and melanotan-II on food
      intake in rats with paraventricular nucleus lesions.
AB  - Bilateral lesions of the hypothalamic paraventricular nuclei (PVN) induce
      hyperphagia and obesity, and ghrelin stimulates appetite in rodents and humans.
      Conversely, corticotrophin-releasing hormone (CRH) and melanotan-II (MT-II, a
      synthetic structural homologue of alpha-melanocyte-stimulating hormone, alphaMSH)
      inhibit feeding behavior. The purpose of the present study was to determine
      whether these peptides are involved in the hyperphagia and obesity induced by PVN
      lesions. After bilateral electrolytic lesions of the PVN, rats were given ghrelin
      intraperitoneally (i. p.), or intracerebroventricular (i. c. v.) infusion of CRH
      or MT-II. We measured the cumulative food intake (FI) for 4 h after ghrelin
      injection in rats fed AD LIB, and the changes in FI at 15 min, 30 min, 1 h, and 2
      h after infusion of CRH and MT-II in rats fasted for 24 h. Ghrelin significantly
      increased cumulative FI, with maximal response 3 h and 4 h after injection, and
      at these times, the FI of PVN-lesioned rats was greater than that of sham
      operated rats. CRH significantly decreased FI in all experimental animals, but at
      1 h, there was a more powerful inhibitory effect on FI in the PVN-lesioned group
      than in the sham-operated group. MT-II decreased FI in sham-operated, but not in
      PVN-lesioned rats. Thus, ghrelin and CRH showed more potent orexigenic and
      anorectic effects in PVN-lesioned rats, respectively, but MT-II lost its
      inhibitory action on feeding behavior. These results suggest that the hyperphagia
      and obesity induced by PVN lesions may be related to an increased orexigenic
      action of ghrelin due to the destruction of endogenous CRH and alphaMSH
      receptors.

PMID- 18058603
TI  - Reduced TGF-beta1 expression and its target genes in human insulinomas.
AB  - Aiming to identify signalling pathways relevant for ss-cell growth we performed
      an explorative micro-array analysis comparing the gene expression profiles of
      three human insulinomas and one normal pancreatic islet preparation. This
      revealed an insulinoma-associated down-regulation of the transforming growth
      factor beta 1 (TGF-beta1) and its target genes. Comparative quantitative real
      time PCR (qRT-PCR) including an expanded sample number of both insulinomas (n=9)
      and pancreatic islet preparations (n=4) confirmed the decreased TGF-beta1
      expression and its target molecules (TGFBI, NNMT, RPN2) in insulinomas.
      Similarly, TGF-beta1 immunofluorescence analysis revealed reduced expression in
      insulinomas when compared to pancreatic islets. In contrast, TGFBR2 (transforming
      growth factor beta receptor II) was found up-regulated. However, the consistent
      down-regulation of the TGF-beta1 targets TGFBI (transforming growth factor, beta
      induced), NNMT (nicotinamide N-methyltransferase), RPN2 (ribophorin II) indicates
      that the parallel up-regulation of TGFBR2 does not compensate for the only
      marginal TGF-beta1 expression levels in insulinomas. TGFBR2 expression was
      confirmed at the protein level in insulinomas. SMAD2/3 protein expression was
      found at higher levels in human pancreatic islets when compared with insulinomas
      by dual colour confocal microscopy. TGF-beta1 signalling is known to be involved
      in cell replication and is abrogated in ductal pancreatic tumours. The down
      regulation of TGF-beta1 expression and its target molecules in insulinomas is a
      new aspect of this cytokine. Our data underline parallels in endocrine and
      exocrine pancreatic tumour development, which may implicate common progenitor
      cells.

PMID- 18058604
TI  - Cholecystokinin (CCK) receptor and CCK gene expression in human pituitary
      adenomas and in vitro effects of CCK peptides on GH and gonadotrophin secretion.
AB  - There is growing evidence that cholecystokinin (CCK) affects growth and
      differentiation of anterior pituitary cells, via the CCK-B receptor. The
      possibility of an autocrine / paracrine role for CCK to modulate hormone
      secretion in human pituitary tumour cells is demonstrated here by RT-PCR and
      direct sequencing. In support of this conclusion, a neutralising antibody against
      the CCK peptide exhibited a dose dependent inhibition of hormone secretion by
      functionless pituitary adenomas. Total RNA was extracted from human pituitary
      adenomas, reverse transcribed into cDNA and subjected to PCR using primers
      specific for the gene for CCK, CCK-A and CCK-B receptors. PCR bands of the
      predicted length were observed in all tumours using human CCK gene and CCK-B
      receptor primers. Restriction digestion and direct sequence analysis provided
      further evidence that they represented both the human CCK peptide along with the
      CCK-A and/B receptor mRNA. CCK-33 and CCK octapeptide sulphate (CCK-8s) both
      powerfully stimulated phosphatidylinositol hydrolysis, providing evidence for
      functional activity of the CCK-A and/B receptors. A direct stimulatory effect of
      CCK peptides on both LH and FSH secretion is reported for the first time, whereas
      stimulatory effects on GH were blocked by antagonists to CCK. These results may
      indicate an autocrine role for CCK in the functioning and perhaps development of
      human pituitary tumours.

PMID- 18058605
TI  - 124-iodine positron emission tomography/computed tomography dosimetry in
      pediatric patients with differentiated thyroid cancer.
AB  - AIM: Publications on 124-iodine (124I-)-positron emission tomography/computed
      tomography (PET/CT) dosimetry contain few if any data on pediatric patients with
      differentiated thyroid carcinoma (DTC). Aim of our study is to determine safety
      and informativeness of 124I-PET/CT dosimetry in DTC patients<or=18 yrs old.
      MATERIAL AND METHODS: We retrospectively analysed the data of 3 years of
      consecutive procedures (n-5) in children (n-4, 11-15 years). We acquired whole
      body 124I-PET emission data 4, 24, 48, 72 and 96 hr, and 124I-PET/CT data 25 hr
      after oral 124I administration (22-26 MBq). Using these data, we calculated the
      thyroid remnant or metastatic lesion dose in Gy per GBq of 131-iodine (131I)
      (RDpA or LDpA, respectively). We measured with a well counter radiation counts of
      blood samples taken at 2, 4, 24, 48, 72 and 96 hr, and with an uncollimated NaI
      detector, whole-body clearance at approximately those times. Using these data, we
      calculated each patient's critical blood activity (CBA), the maximum 131I
      activity avoiding the putative>2Gy blood dose portending serious myelotoxicity.
      RESULTS: Besides hypothyroid fatigue, no symptoms were noted. In 4 dosimetry
      procedures before the first radioiodine therapy, RDpAs were generally high
      (median 288 Gy/GBq, range 59-648 Gy/GBq). LDpAs (4 lymph node metastases) were
      much lower (median 6.5 Gy/GBq, range 1-9 Gy/GBq). CBAs were high (median 26 GBq,
      range 19-42, n=5). Disease management was modified or disease extent clarified in
      2/4 patients. CONCLUSIONS: A standard adult 124I-PET/CT dosimetry protocol
      appears to be safe and informative in pediatric DTC patients.

PMID- 18058606
TI  - Unusual adrenal metastasis and abdominal carcinomatosis secondary to Hurthle cell
      carcinoma of the thyroid.
AB  - Hurthle cell carcinoma (HCC) of the thyroid is an uncommon and relatively rare
      differentiated thyroid neoplasm. To our knowledge, no reported case of adrenal
      metastases with abdominal carcinomatosis secondary to HCC of the thyroid has been
      demonstrated by F-18 FDG PET/CT imaging. One report of adrenal uptake on I-131
      whole-body scan with HCC exists. In this case report, we describe a patient with
      HCC who had a left adrenal metastasis with abdominal carcinomatosis that was
      discovered using F-18 FDG PET/CT imaging.

PMID- 18058608
TI  - Antibacterial lignans and triterpenoids from Rostellularia procumbens.
AB  - One new lignan, rostellulin A ( 1), four known lignans, justin B ( 2), justicidin
      C ( 3), cilinaphthalide A ( 4), and justicidin A ( 5), and four known
      triterpenoids, ursolic acid ( 6), euscaphic acid ( 7), 2 alpha-hydroxyursolic
      acid ( 8), and tormentic acid ( 9), have been isolated from the whole plants of
      Rostellularia procumbens. Their structures were established on the basis of
      spectral data, including extensive NMR experiments. To our knowledge, compounds 6
      - 9 are known compounds but not previously isolated from R. procumbens, 4 was
      previously reported from other Rostellularia species. Antibacterial activities of
      1 - 9 were evaluated against eight bacterial strains with the agar dilution
      method, and they were found to possess antimicrobial activity with MIC values in
      the range of 1.56 - 100 microg/mL. None of the lignans exhibited cytotoxic
      activity against HCT-8 and Bel-7402 cells at concentrations up to 5 microg/mL.

PMID- 18058609
TI  - Effect of triterpenoids isolated from the floral spikes of Betula platyphylla
      var. japonica on P-glycoprotein function.
AB  - One of the major causes of multidrug resistance (MDR) in cancer cells is over
      expression of P-glycoprotein (P-gp). We studied the effects of 20 triterpenes
      isolated from the floral spikes of Betula platyphylla var. japonica ( B.
      platyphylla) on P-gp function based on our previous finding that some of them
      showed MDR reversing effects. We evaluated accumulations and effluxes of
      rhodamine 123 as a P-gp substrate with P-gp over-expressing KB-C2 cells. Among
      the 20 triterpenes, compounds 3, 4, 8, 9, 13, 15, and 20 increased rhodamine 123
      accumulations in KB-C2 cells, and three ( 8, 13, and 20) of them also inhibited
      efflux of rhodamine 123 out of cells. In addition, compounds 13 and 20 showed a
      weak inhibitory activity of P-gp ATPase. These results suggested that MDR
      reversing effects of compounds 13 and 20 are partly involved in inhibition of P
      gp ATPase.

PMID- 18058610
TI  - Evaluation of the topical anti-inflammatory activity of ginger dry extracts from
      solutions and plasters.
AB  - In this study the skin permeation and the topical anti-inflammatory properties of
      ginger extracts were investigated. A commercial ginger dry extract (DE) and a
      gingerols-enriched dry extract (EDE) were evaluated for their in vivo topical
      anti-inflammatory activity by inhibition of Croton oil-induced ear oedema in
      mice. Furthermore, the feasibility of an anti-inflammatory plaster containing DE
      or EDE was evaluated. Since the in vivo activity was evaluated in mice, the ex
      vivo skin permeation study was performed by using mouse skin or human epidermis.
      The DE from the acetonic solution exerted a dose-dependent topical anti
      inflammatory activity (ID (50) = 142 microg/cm (2)), not far from that of the
      potent reference substance indomethacin (ID (50) = 93 microg/cm (2)). Similarly,
      the EDE induced a dose-dependent oedema reduction though its potency (ID (50) =
      181 microg/cm (2)) was slightly lower than that of DE. Increase of the 6-gingerol
      concentration in the extract did not improve the anti-inflammatory activity. The
      medicated plasters, containing 1 mg/cm (2) of the commercial DE or EDE, had good
      technological characteristics and exerted a significant antiphlogistic effect,
      too. By using the plaster containing EDE, the 6-gingerol amount that permeated
      through human epidermis was 6.9 microg/cm (2) while the amount that passed
      through mouse skin was 22.1 microg/cm (2). Nevertheless, the amounts of 6
      gingerol permeated through human epidermis and mouse skin in the early period
      (8h) were comparable (p > 0.3). This preliminary result suggests that the anti
      inflammatory effect observed in mice could also be exerted in humans.

PMID- 18058611
TI  - Investigation of phenolic constituents in Echinacea purpurea grown in China.
AB  - Echinacea is a North American native medicinal herb. In 1990 s, it was introduced
      in China. Nowadays, Echinacea is growing successfully in a number of places in
      China, and has been used as a crude drug. However, the phytochemical variation in
      the plant grown in China has not been studied. In this study, the contents of
      total phenolics and caffeic acid derivatives in aerial parts and roots of
      Echinacea purpurea grown in China were investigated by high-performance liquid
      chromatography (HPLC) and colorimetric analysis. The effects of different drying
      methods on the components were also studied. The results show that the content of
      caffeic acid derivatives in E. purpurea reached its highest in the middle stage
      of full blossoming. The content of caffeic acid derivatives in fresh raw material
      was generally higher than that in dried raw material. There was no significant
      difference in the content of caffeic acid derivatives among three geographical
      populations of E. purpurea. Furthermore, the developmental pattern of total
      phenolics in E. purpurea was the same as that of caffeic acid derivatives. The
      stage of mid-bloom is an optimal harvesting period for both caffeic acid
      derivatives and total phenolics. In addition, the results show that the fresh raw
      material is the optimal material for pharmaceutical purposes, and that the
      optimal pharmaceutical parts are the roots, leaves and flowers.

PMID- 18058612
TI  - Mycological and electron microscopic study of Solanum chrysotrichum saponin SC-2
      antifungal activity on Candida species of medical significance.
AB  - Solanum chrysotrichum is utilized in traditional Mexican medicine for the
      treatment of mycotic skin infections. Several microbiological studies have
      provided evidence of its antifungal activity against dermatophytes and yeasts. S.
      chrysotrichum saponins have been identified as a group of compounds with
      antifungal activity and saponin SC-2 has demonstrated to be the most active.
      Previous clinical studies have shown the therapeutic effectiveness of S.
      chrysotrichum-derived saponin-standardized herbal products in the treatment of
      Tinea pedis and Pityriasis capitis. There is no previous evidence of the activity
      of these saponins against Candida non-albicans species, or fluconazole- and
      ketoconazole-resistant Candida strains. The present study reports the biological
      activity of the SC-2 saponin (inhibitory concentration [IC (50)] and minimum
      fungicide concentration [MFC]), against 12 Candida strains of clinical
      significance ( C. albicans, five strains; C. glabrata and C. parapsilosis, two;
      C. krusei, C. lusitaniae and C. tropicalis, one), including some fluconazole
      (Fluco)- and ketoconazole (Keto)-resistant clinical isolates. In addition, SC-2
      associated microstructural alterations were reported in four of the above
      mentioned Candida species. Seven strains had IC (50) of 200 microg/mL for SC-2,
      400 microg/mL was found in four strains, and 800 microg/mL for a sole C. glabrata
      strain. Susceptibility to SC-2 saponin was as follows: C. albicans = C.
      lusitaniae > C. krusei > C. glabrata. The MFC was 800 microg/mL for the majority
      of strains (nine), 400 microg/mL for C. albicans (two strains) and C. lusitaniae.
      The ultrastructural Candida changes originated by SC-2 included the following: 1)
      damage on cytoplasmic membrane and organelles; 2) changes in cell wall morphology
      and density, with separation of cytoplasmatic membrane from cell wall and
      disintegration of the latter; and 3) total degradation of cellular components and
      death. Changes were manifested from 6 h of incubation, reaching their maximum
      effect at 48 h. In conclusion, the saponin SC-2 possesses fungicide and
      fungistatic activity on different Candida albicans and non- albicans species
      (including some azole-resistant strains) with IC (50) values of 200 microg/mL (in
      Fluco-susceptible strains) and of 400 - 800 mug/mL (in Fluco-resistant strains).
      Additionally, we observed by transmission electron microscopy (TEM) that saponin
      SC-2 causes severe changes in all fungal cell membranes, and to a lesser degree
      on the cell wall.

PMID- 18058613
TI  - Novel single-balloon enteroscopy for diagnosis and treatment of the small
      intestine: preliminary experiences.
AB  - BACKGROUND AND AIM: As a tool for examining the small intestine, double-balloon
      enteroscopy (DBE) has been used routinely. However, there remain a few issues
      relating to the handling of DBE, such as attaching a balloon to the tip of the
      scope, and inflating/deflating the two balloon systems. Recently, we developed a
      novel single-balloon enteroscopy (SBE) system for the examination of the small
      intestine. The aim of the present study was to evaluate the insertion technique,
      the safety, and the clinical impact of the SBE system. PATIENTS AND METHODS:
      Between January 2006 and June 2007, all patients undergoing enteroscopy with the
      Olympus SBE system (length 200 cm, outer diameter 9.2 mm) were studied. Instead
      of a balloon attached to the distal scope end, the distal scope end was hook
      shaped, and manipulating the up-angle or down-angle of the scope end enabled
      exploration of the small intestine. RESULTS: A total of 78 procedures were
      performed in 41 patients (24 men, 17 women; mean age 48.9 years, range 23 - 85
      years). The indications for the examination were suspected mid-gastrointestinal
      bleeding (n = 12), Crohn's disease (n = 17), abdominal pain (n = 8), and
      abdominal tumor (n = 4). The mean procedure time was 62.8 +/- 20.2 minutes and
      70.4 +/- 19.3 minutes for the oral and anal routes, respectively. Among 24
      patients in whom total enteroscopy was attempted, the entire small intestine was
      explored in 6. CONCLUSION: SBE is not only easy to perform, due to the single
      balloon, but it can also safely examine the deep small intestine. Therefore, SBE
      may be a useful diagnostic and therapeutic tool in addition to DBE for
      investigating suspected small bowel disease.

PMID- 18058614
TI  - Miniprobe EUS in the pretherapeutic assessment of early esophageal neoplasia.
AB  - BACKGROUND AND STUDY AIMS: The high-frequency endosonography miniprobe has been
      advocated prior to endoscopic treatment of superficial esophageal neoplasm. We
      conducted a retrospective study, which summarized our clinical experience with
      various miniprobe techniques in the assessment of early squamous cell carcinoma
      (SCC) and superficial adenocarcinoma on Barrett's mucosa (SAB). PATIENTS AND
      METHODS: A total of 106 superficial and naive esophageal lesions were included in
      this series (52 SAB, 54 SCC). The results of the miniprobe staging were compared
      with pathology in order to determine the accuracy of this technique in
      differentiating mucosal from submucosal infiltration. Secondary aims were a
      comparison between the frequencies (20- vs. 30-MHz) and coupling methods (water
      filled lumen vs. balloon-sheathed catheter) used. RESULTS: Overall accuracy,
      sensitivity, and specificity to differentiate T1sm from T1 m tumors were 73.5 %,
      62 %, and 76.5 %, respectively. Overdiagnosis occurred in 18.6 % of the lesions.
      No statistically significant difference was found in the accuracy of the
      miniprobe staging between the two lesion types (SCC and SAB) ( P = 0.65), and
      results were significantly poorer in the distal part of the esophagus ( P =
      0.00039). No significant difference was found between the two frequencies ( P =
      0.51). Water-filled lumen proved to be superior to the balloon-sheathed catheter
      ( P = 0.015). CONCLUSION: High-frequency miniprobe examination has a limited
      accuracy in the detection of submucosal invasion in early esophageal cancer.
      Further improvements in acoustic coupling and ultrasound technique are required
      to improve the miniprobe accuracy before its implementation into clinical
      routine.

PMID- 18058615
TI  - The safety of fine-needle aspiration guided by endoscopic ultrasound: a
      prospective study.
AB  - BACKGROUND AND STUDY AIMS: Fine-needle aspiration (FNA) is commonly performed in
      conjunction with endoscopic ultrasound (EUS) procedures. The complication rate
      associated with FNA is considered to be low but requires further evaluation with
      prospective studies. PATIENTS AND METHODS: A total of 483 consecutive patients
      who underwent EUS-guided FNA over a 12-month period were prospectively enrolled
      in the study. The patients were screened for postprocedural complications,
      including abdominal pain, nausea, vomiting, and gastrointestinal bleeding.
      Complications were assessed immediately after EUS-FNA and 30 days later with a
      telephone call, when inquiries were made about emergency room and physician's
      office visits or hospitalizations during this 30-day period. RESULTS: Complete
      information was obtained from 414 patients (86 %). Complications occurred in
      seven patients during the first day. Five of these patients had unplanned
      admissions to hospital: two patients were observed because they had abdominal
      pain after FNA of pancreatic cysts; one patient was observed because they
      developed chest pain after mediastinal lymph node FNA; and two patients were
      monitored after celiac node FNA, one with a transient fever and one with self
      limited melena. All five of these patients were discharged within 24 hours of
      admission, none required blood transfusion, and none showed any evidence of
      pancreatitis or infection. Two other patients visited the emergency department
      but were discharged on oral analgesics after appropriate evaluation. By day 30
      six patients had died as a result of their primary disease process. There was no
      unexpected morbidity or mortality attributable to the EUS-FNA. CONCLUSIONS: FNA
      is a safe intervention in patients undergoing EUS in a high-volume academic
      center, with a low postprocedural complication rate.

PMID- 18058616
TI  - Ulcers and gastritis.

PMID- 18058617
TI  - Upper gastrointestinal tumors.

PMID- 18058618
TI  - Biliary ERCP.

PMID- 18058619
TI  - Innovations.

PMID- 18058620
TI  - Gastroesophageal reflux disease and Barrett's esophagus.

PMID- 18058621
TI  - Splenic injury after colonoscopy.
AB  - Splenic injury is a rare and serious complication of colonoscopy. The most likely
      mechanism is tension on the splenocolic ligament and adhesions. Eight cases were
      identified among claims for compensation submitted to the Danish Patient
      Insurance Association during the period 1992-2006, seven of which were reported
      after 2000. The total number of colonoscopies in Denmark in 2004 was 39 067.
      Seven of the eight patients were aged 65 years or over. Loops causing
      difficulties during the colonoscopy had been reported in four patients. All the
      patients had a symptom-free interval after the colonoscopy, ranging from 4 hours
      to 7 days, before presenting with signs of splenic injury. In all cases the
      spleen was torn, and the amount of blood in the peritoneal cavity ranged from
      1500 mL to 5000 mL. Two patients died postoperatively. The number of cases
      reported after 2000 indicates that this potentially lethal complication might be
      more common than was previously assumed, and it is possibly under-reported.
      Preventive measures include good colonoscopic technique to avoid loop formation
      and the use of excessive force; and it is possible that emerging endoscopic
      technologies will lead to a reduced risk of splenic injury. The information given
      to patients both before and after the procedure should include information on the
      signs of this complication, and patients should be also informed that these signs
      can develop after a symptom-free interval.

PMID- 18058622
TI  - High-dose vitamin D supplementation in children with cerebral palsy or
      neuromuscular disorder.
AB  - Adequate vitamin D levels are essential for normal skeletal development and
      mineralization. This is particularly important in children with cerebral palsy or
      other neuromuscular disorders who are at an increased risk of osteoporosis. The
      aim of this study was to evaluate the effect of high-dose vitamin D3
      supplementation on vitamin D status in 44 disabled children. Vitamin D was
      administered during school days (1000 IU vitamin D3 per orally five days per week
      for 10 weeks) to half of the children (N=21) while the others (N=23) continued
      without supplementation. At baseline the median serum 25-hydroxyvitamin D was 44
      nmol/L (range 26-82 nmol/L). The concentration increased significantly during the
      10 weeks intervention in the supplemented group (median 56 nmol/L, range 39-88
      nmol/L; p=0.012 for the difference from baseline) and decreased in the control
      group (median 37 nmol/L, range 24-74 nmol/L; p=0.038). No significant changes in
      any of the other measured parameters were observed. Hypovitaminosis D is
      prevalent in disabled children. Supplementation with 1000 IU vitamin D3 perorally
      five days per week results in a significant increase in vitamin D level and is
      not associated with hypercalcemia or other adverse effects.

PMID- 18058623
TI  - Clinical utility of electrophysiological evaluation in Crigler-Najjar syndrome.
AB  - We evaluated the neurological and neurophysiological features in ten patients
      with genetically characterized Crigler-Najjar (CN) syndrome: four with typical
      type I CN had undergone orthotopic liver transplantation (OLT); six had type II
      CN, and three of them developed severe hyperbilirubinemia with a limited response
      to phenobarbital leading to an intermediate phenotype I/II. Clinical neurological
      and multimodal electrophysiological evaluations [electroencephalogram (EEG),
      visual (VEPs), motor (MEPs) and brainstem auditory (BAEPs) evoked potentials]
      were performed. Neurological examinations showed mild hand tremor in four
      patients (one pre-OLT and one post-OLT type I, two type I/II). EEG revealed high
      voltage paroxysmal discharges in four patients (three type I/II, and one type I
      with a marked improvement after OLT). VEPs showed P100 wave increased latency in
      five patients (three type I, and two type I/II considered for OLT evaluation).
      MEPs showed prolonged central motor conduction time in five patients (two type I;
      one type I/II; two type II). Only EEG and VEPs findings showed a correlation with
      high bilirubin levels. BAEPs were normal. In conclusion, VEPs and EEG contribute
      to identify and monitor bilirubin neurotoxic effects, and may play a decisional
      role in some cases of severe hyperbilirubinemia without overt neurologic damage.

PMID- 18058624
TI  - Folate receptor autoantibodies and spinal fluid 5-methyltetrahydrofolate
      deficiency in Rett syndrome.
AB  - Rett syndrome was associated with low cerebrospinal fluid (CSF) 5
      methyltetrahydrofolate (5MTHF) in 42-50% of European patients whereas
      approximately 93% of the patients from North-America had a normal CSF 5MTHF
      status. We determined the CSF folate status in Rett patients living in North- and
      South-Western Europe and measured serum folate receptor (FR) autoantibodies of
      the blocking type to explain the reduced folate transport across the choroid
      plexus. Irrespective of their MECP2 genotype and despite normal plasma folate
      values, 14 of 33 Rett patients (42%) had low CSF folate levels. Blocking FR
      autoantibodies were found in 8 of the Rett patients (24%), 6 of whom had low CSF
      folate levels. FR autoimmunity was primarily found within the group of Rett
      patients with low CSF folate status with a higher incidence in North-Western
      Europe. In Rett patients from North-America 74 of 76 girls had higher folate
      values in both serum and CSF than European patients. The food folate
      fortification in North-America may account for the higher folate levels and may
      prevent CFD in these Rett patients. FR autoimmunity occurred predominantly in
      Rett patients from North-Western Europe and may contribute to cerebral folate
      deficiency (CFD).

PMID- 18058625
TI  - Mitochondrial complex I encephalomyopathy and cerebral 5-methyltetrahydrofolate
      deficiency.
AB  - Folate transport to the brain depends on ATP-driven folate receptor-mediated
      transport across choroid plexus epithelial cells. Failure of ATP production in
      Kearns-Sayre syndrome syndrome provides one explanation for the finding of low
      spinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF) levels in this condition.
      Therefore, we suspect the presence of reduced folate transport across the blood
      spinal fluid barrier in other mitochondrial encephalopathies. In the present
      patient with mitochondrial complex I encephalomyopathy a low 5
      methyltetrahydrofolate level was found in the CSF. Serum folate receptor
      autoantibodies were negative and could not explain the low spinal fluid folate
      levels. The epileptic seizures did not respond to primidone monotherapy, but
      addition of ubiquinone-10 and radical scavengers reduced seizure frequency. Add
      on treatment with folinic acid led to partial clinical improvement including full
      control of epilepsy, followed by marked recovery from demyelination of the
      brainstem, thalamus, basal ganglia and white matter. Cerebral folate deficiency
      is not only present in Kearns-Sayre syndrome but may also be secondary to the
      failure of mitochondrial ATP production in other mitochondrial encephalopathies.
      Treatment with folinic acid in addition to supplementation with radical
      scavengers and cofactors of deficient respiratory enzymes can result in partial
      clinical improvement and reversal of abnormal myelination patterns on neuro
      imaging.

PMID- 18058626
TI  - Aicardi syndrome: follow-up investigation of Swedish children born in 1975-2002.
AB  - Aicardi syndrome has been defined by the triad of agenesis of the corpus
      callosum, early seizure onset and lacunar chorioretinopathy. In a nation-wide
      survey a total of 18 Swedish cases were found. Fourteen girls were re-examined by
      one of the authors at the ages of 1-27 years. One was seizure free following
      epilepsy surgery operation, 13 were drug resistant. Two were on ketogenic diet.
      Most of the girls had multifocal EEG discharges. All except one were severely
      disabled with severe mental retardation and total dependency on helpers for
      activities of daily life. Communication, nutrition, and motor function were
      severely affected areas. Visual function was difficult to evaluate because of
      mental retardation and lack of co-operation and varied from severely impaired to
      normal. In one case the appearance of the ocular fundus was documented to have
      changed with time. One girl was exceptional and seizure free with mild mental
      retardation. An update by March 2006 showed that 12/18 patients were still alive,
      at a median age of 13.5 years (range: 3-31 years). Six had died between the ages
      of 3-10 years. They had all suffered from intractable epilepsy and belonged to
      the most disabled group. Surprisingly two had died from malignant brain tumours.

PMID- 18058627
TI  - Predictive power of first morning glucose and the ketogenic diet.
AB  - The purpose of this study was to determine if hypoglycemia or hyperglycemia
      predicts the response to a ketogenic diet (KD) in a cohort of children with
      intractable epilepsy. We evaluated whether morning blood glucose during the
      initial 21 days after initiation of the KD in children with IE was related to
      seizure reduction after 3 months of treatment. The relation between change in
      weight status and blood glucose was also explored. Fasting morning whole blood
      glucose was measured each day for the first 21 days after initiation of KD.
      Weight and height were obtained at baseline, day of discharge, and at 0.5 and 1
      month of full KD therapy. Associations among clinical response to the KD
      (responder status defined as >50% reduction of seizure frequency at 3 months),
      hypoglycemia, hyperglycemia, style of KD initiation protocol (fasting or gradual)
      and weight status were evaluated. Forty-five subjects age 1-12 years were
      enrolled. KD responder status was not associated with low or elevated blood
      glucose or type of initiation style protocol. Variability in day-to-day blood
      glucose also did not predict response to KD. Children who had declining weight
      status during KD initiation were more likely to be hypoglycemic during full KD
      therapy. Low blood glucose during KD therapy was not necessary for clinically
      significant seizure reduction. Hypoglycemia was related to declining weight
      status irrespective of initiation style protocol. An effective KD can be provided
      in a manner to minimize side-effects and maximize efficacy.

PMID- 18058628
TI  - Seizures, psychosis and coma: severe course of hashimoto encephalopathy in a six
      year-old girl.
AB  - Hashimoto encephalopathy (HE) is a rare steroid-responsive encephalopathy
      associated with elevated antithyroid antibodies and is a well recognised
      complication of autoimmune thyroid disease. The clinical picture is pleomorphic,
      presenting with variable symptoms like coma, seizures, neuropsychiatric changes
      (impairment of cognitive functions, behavioural and mood disturbances,
      hallucinations) or focal neurological deficits. HE is mainly diagnosed in adults,
      but also a rare differential diagnosis of encephalopathy or epilepsy in children.
      The diagnosis is often overlooked at presentation but is crucial as it is a
      treatable disease. We report on the youngest patient described up to now
      presenting with progressive epilepsy resistant to anticonvulsive treatment and
      unclear encephalopathy related to Hashimoto thyroiditis.

PMID- 18058629
TI  - Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and
      hydrocephalus (MPPH): report of a new case.
AB  - Megalencephaly (MEG), or enlargement of the brain, can either represent a
      familial variant with normal cerebral structure, or a rare brain malformation
      associated with developmental delay and neurological problems. MEG has been split
      into two subtypes: anatomical and metabolic. The latter features a build-up
      inside the cells owing to metabolic causes. Anatomical MEG has been detected in
      many different conditions, including many overgrowth syndromes. In 2004 Mirzaa et
      al. reported five non-consanguineous patients with a new MCA/MR syndrome
      characterized by severe congenital MEG with polymicrogyria (PMG), postaxial
      polydactyly (POLY) and hydrocephalus (HYD). The authors argued that these
      findings identified a new and distinct malformation syndrome, which they named
      MPPH. We report on a new case of MPPH, the first to be described after the
      original series (Mirzaa et al., 2004).

PMID- 18058630
TI  - Atypical presentation of Prader-Willi syndrome with cerebral venous thrombosis:
      association or fortuity?
AB  - A newborn female born at term was admitted at 28 hours for seizures and
      generalized hypotonia. Cerebral ultrasound showed a right temporal echogenic
      lesion confirmed on MRI and thought to be secondary to thrombosis of the vein of
      Labbe. The EEG showed epileptic discharges over the right temporal region.
      Extensive thrombotic studies revealed a transiently decreased PTT consistent with
      a prothrombotic state. The hypotonia did not resolve after the acute phase as
      expected, raising the possibility of another underlying cause. Because of a
      peculiar phenotype with almond-shaped eyes and bitemporal depression, Prader
      Willi syndrome (PWS) was suspected. Methylation analysis confirmed PWS, FISH
      analysis excluded a deletion in 15q11-q13, maternal uniparental disomy (UPD) was
      confirmed. To our knowledge, this is the first report of the association of a
      neonatal venous thrombosis and a PW Syndrome.

PMID- 18058631
TI  - Investigation of recessive ataxia loci in patients with young age of onset.
AB  - Autosomal recessive cerebellar ataxias are a phenotypically and genetically
      heterogeneous group of diseases. Major forms can be distinguished on the basis of
      clinical signs, age of onset, biochemical parameters or genotypes. To develop
      rational diagnostic strategies, phenotypic information, e.g., age of onset
      combined with population-specific disease frequencies could be highly favourable.
      We tested this hypothesis for single candidate loci and mutations in North
      European ataxia patients with juvenile and early adult onset. While we could
      prove that Friedreich ataxia (FRDA) is frequent in Germany, only few patients
      with ataxia-oculomotor apraxia type 1 (AOA1) and type 2 (AOA2) were diagnosed.
      The frequency of the mitochondrial recessive ataxia syndrome (MIRAS) and the
      infantile onset spinocerebellar ataxia (IOSCA) in this population remains unknown
      since no case with the common mutation of the corresponding gene was detected.

PMID- 18058632
TI  - Brainstem disconnection: case report and review of the literature.
AB  - We report a neonate with brainstem disconnection. Only five similar cases have
      previously been described, the longest survival was 7 weeks. The newborn
      exhibited muscular hypertonia, absent suction, insufficient breathing, and
      seizures. Magnetic resonance imaging showed a disconnection between the upper
      pons and the medulla oblongata and cerebellar hypoplasia. The basilar artery was
      not visible. These neuroimaging findings are clearly different from other
      midbrain or hindbrain malformations with cerebellar hypoplasia. This pattern and
      a previously reported autopsy point to a malformation, not a disruption.

PMID- 18058633
TI  - Tyrosine hydroxylase deficiency presenting with a biphasic clinical course.
AB  - Tyrosine hydroxylase deficiency, a cause of the autosomal recessive form of L
      DOPA responsive dystonia, has been associated with a broad spectrum of movement
      disorders and clinical courses. We describe a new patient presenting with an
      early onset spastic paraplegia who later developed a progressive generalized
      dystonic-dyskinetic syndrome. He markedly improved with a very low dosage of L
      DOPA/carbidopa, while higher dosages were not tolerated. Two novel mutations
      (p.G414R/p.L510Q) were detected in the TH gene.

PMID- 18058634
TI  - [High-resolution magnetic resonance imaging of carotid atherosclerotic plaque].
AB  - Stroke is the third most common cause of mortality in the United States with an
      incidence rate of approximately 700 000 deaths per year. As a means to prevent
      cerebrovascular events, current concepts advocate endarterectomy or carotid
      stenting in patients with advanced carotid disease. Arterial stenosis alone has
      been shown to be a poor predictor of cardiovascular events and therefore both
      arterial stenosis and patient symptom status are taken as indications for
      interventional therapy. Several studies have shown that symptomatic subjects
      benefit more from a carotid endarterectomy than asymptomatic subjects: 3-6
      carotid endarterectomies are needed to prevent one stroke per year in symptomatic
      subjects with > 70 % stenosis compared to 14 - 17 carotid endarterectomies in
      asymptomatic patients with > 50 % stenosis. It is commonly accepted today that
      factors other than the degree of luminal stenosis can determine a patient's
      symptom status, such as the composition or the superficial structure of
      atherosclerotic plaque. High-resolution magnetic resonance imaging has overcome
      the limitations of current angiographic techniques and has emerged as a leading
      non-invasive imaging modality for atherosclerotic disease, especially within
      carotid arteries and other large vessels. In this review, the state of the art in
      MRI of atherosclerosis is presented in terms of hardware and image acquisition
      protocols. Also, the results of validation studies for measuring lesion size,
      composition and inflammation will be summarized. Finally, the status of several
      clinical trials involving MRI of atherosclerosis will be reviewed.

PMID- 18058635
TI  - [Flat-panel CT as a new perinterventional imaging modality in aortic stentgraft
      procedures--work in progress].
AB  - PURPOSE: To evaluate the value of flat-panel CT (FP-CT) as a new
      perinterventional imaging modality in aortic stentgraft procedures. MATERIALS AND
      METHODS: FP-CT was performed in 21 patients (19 males, mean age 77, range 54 to
      90) from June 2005 to February 2007 immediately after endovascular treatment of
      thoracic and abdominal aortic aneurysms on the angiographic table. Nine thoracic
      aortic aneurysms were treated with Zenith-endoprosthesis. Nine of twelve
      abdominal aortic aneurysms were treated with Zenith-endoprosthesis and three with
      an Excluder-endoprosthesis. Images were acquired with a rotating C-arm and the
      following parameters: during an acquisition time of 20 seconds and at a rotation
      of 217 degrees, 538 projections were acquired. Contrast agent was administered in
      14 patients. Images were displayed in MIP, MPR and VRT mode. RESULTS: In all
      patients the stentgraft was shown exactly and the alignment of the prosthesis
      along the landing zones was well displayed. The aneurismal sack was well shown in
      all patients. 1 x an endoleak II was detected, 1 x an angiographically verified
      endoleak I was not detected. In one patient distal extension was considered due
      to suspected short stentgraft at the distal neck. Flat-panel CT showed sufficient
      neck coverage and no extension was inserted. Due to artifacts of the prosthesis,
      the platinum markers and the guide wire as well as due to pulsation of the aorta,
      the resolution of detail decreased and reduced the visualization of the
      alignment. CONCLUSION: FP-CT is a promising tool and may provide additional
      information, but further studies are necessary to define the value of flat-panel
      CT in thoracic and abdominal aortic stentgraft procedures.

PMID- 18058636
TI  - [Cost-effectiveness of percutaneous core needle breast biopsy (CNBB) versus open
      surgical biopsy (OSB) of nonpalpable breast lesions: metaanalysis and cost
      evaluation for German-speaking countries].
AB  - PURPOSE: To analyze the cost-effectiveness of percutaneous image-guided CNBB
      (stereotactic-/ultrasound-guided; large/vacuum-assisted) of non-palpable breast
      lesions vs. OSB and to compare and discuss the results reported in the literature
      with results for German-speaking countries. MATERIALS AND METHODS: A key word
      search in three databases, limited to the period from 1/1994 to 12/2006 was
      performed. Only original papers were selected. No published articles for German
      speaking countries were identified; therefore a comprehensive data collection was
      made. RESULTS: On the basis of 377 abstracts, nine studies were evaluated for
      final assessment. The data of German-speaking countries were compared with
      results reported in the literature. This study demonstrates that CNBB compared to
      OSB leads to reduction in cost ranging from 51-96 %. The cost reduction depends
      on biopsy modality and lesion type and is subject to national fluctuations. CNBB
      can replace a surgical procedure in 71-85 % of cases. CONCLUSION: Use of CNBB as
      an alternative to OSB has the potential to substantially reduce healthcare costs.
      The data are based almost exclusively on the North American literature. A
      potential cost reduction in the Netherlands and Switzerland confirms these
      findings. Future work must include cost evaluation studies for German-speaking
      countries since this is an issue with important national economic ramifications.

PMID- 18058637
TI  - [Formation of a pseudoaneurysm in the liver after TIPSS implantation in Budd
      Chiari syndrome].

PMID- 18058638
TI  - [Paraganglioma of the orbit--a rare disease].

PMID- 18058639
TI  - [Stent-graft therapy in a mobile thrombus in the thoracic aorta].

PMID- 18058640
TI  - Concept and treatment of hydrocephalus in the Greco-Roman and early Arabic
      medicine.
AB  - In the ancient medical literature hydrocephalus was not often described although
      its existence and symptomatology were well known. Most detailed descriptions of
      hydrocephalus including the surgical treatment are extant in the encyclopaedic
      works on medicine of the physicians Oreibasios and Aetios from Amida from the 4th
      and 6th centuries AD, respectively. Because of their broad scientific interests,
      this type of physicians, typical for the late Roman empire, were known as
      philosophy-physicians (iota alpha tau rho o sigma o phi iota sigma tau alpha
      iota). They defined hydrocephalus in contrast to our present understanding as a
      fluid collection excluding abscesses visible as a bulging tumour localised either
      outside or inside the skull of an infant. They classified the hydrocephalus
      similar as stated first by Galen in the 2nd century AD in four types
      corresponding to the assumed anatomic localisation of the fluid collection: 1st
      Type between the skin and the pericranium corresponding to the subgaleal
      haematoma or caput succedaneum of the newborn in our terminology, 2nd Type
      between the pericranium and the skull corresponding to the cephal haematoma after
      delivery, 3rd Type between skull and the meninges with increased head
      circumference, bone sutures being increasingly driven apart corresponding most
      likely to the hydrocephalus in our understanding, and 4th Type between the
      menings and the brain characterised by severe neurological deficit with lethal
      prognosis corresponding probably to all pathologies which were accompanied by an
      excessive increase of the intracranial pressure with a bulging fontanel. Due to
      the lack of autopsies in ancient times, the hydrocephalus was never linked to the
      pathology of the ventricles. All forms of hydrocephalus were believed to be
      caused by improper handling of the head by the midwife during delivery. Only the
      extracranial fluid collections, but not hydrocephalus in our sense, were
      considered to be suitable for surgical treatment. The surgery consisted in one or
      more incisions and evacuation of the fluid. The wound was not closed but let open
      for three days. Thereafter plasters or sutures closed the incisions. The surgical
      technique goes back probably to Antyllos a surgeon from the 3rd century AD whose
      considerations were cited in the work of Oreibasios. The early Arabic physicians
      took over the surgical indications, the operative technique and modified the
      Greek concept of hydrocephalus. Avicenna separated the traumatic haematomas
      outside the skull from the term hydrocephalus. However Avicenna, as all previous
      authors, had not linked hydrocephalus with the ventricular system. The autopsy of
      a child with an exorbitant hydrocephalus performed by the anatomist Vesalius in
      the 16th century revealed as a single pathology an extremely dilative ventricular
      system filled with water-like fluid which made it necessary to change completely
      the ancient concept of hydrocephalus.

PMID- 18058641
TI  - Long-term outcome of endoscopic third ventriculostomy in obstructive
      hydrocephalus.
AB  - This multicentric study reports on 140 patients who underwent endoscopic third
      ventriculostomy for obstructive hydrocephalus in four Italian neurosurgical
      centers between 1994 and 1999. Its aim is to define the long-term outcome of
      these patients many years (6-12) after the initial procedure. The study includes
      both children and adults; the etiology of the hydrocephalus was malformative
      aqueductal stenosis in 88 cases (62.8%), compression by tumors of the
      mesencephalic and pineal regions and posterior fossa in 45 (32.2%) and post
      infection aqueductal stenosis in 7 (5%). The ETV was performed by using the
      standard technique. The overall rate of good results (shunt-independent patients
      with clinical remission or improvement) was 87.1%. Eighteen patients (12.9%)
      required a shunt because of ETV failure. The long-term outcome of ETV in this
      study was not influenced by the patient's age and the etiology of the
      hydrocephalus (although cases secondary to cisternal hemorrhage and infections
      are not included). Other series including cases with long follow-up are analyzed.
      In conclusion, ETV results in a high rate of good long-term outcome in patients
      with obstructive hydrocephalus. Because postoperative failures occur early,
      clinical and radiological control studies must be performed particularly in the
      first years after the neuroendoscopic procedure.

PMID- 18058642
TI  - Occlusive hydrocephalus associated with cerebellar infarction treated with
      endoscopic third ventriculostomy: report of 5 cases.

PMID- 18058643
TI  - Surgical target selection in cerebral glioma surgery: linking methionine (MET)
      PET image fusion and neuronavigation.
AB  - OBJECTIVE: The objective of this study was to investigate the histological
      correlate of (11)C-methionine (MET) PET uptake of brain gliomas by image fusion
      for navigated surgery. METHODS: Twenty-seven patients (18 male, 9 female; mean
      age 42 years; range 11-77 years; 8 low-grade and 11 high-grade astrocytomas or
      mixed gliomas, 8 oligodendrogliomas) underwent MET PET studies preoperatively.
      RESULTS: MET PET tumor uptake was detected in 26 of 27 patients (96.3%). The
      quantitative MET tumor standardized uptake value (SUV) ratio was significantly
      higher in malignant gliomas and oligodendrogliomas than in low-grade gliomas
      (2.76/2.62 vs. 1.67, p=0.03). Generally, qualitative visual grading of MET uptake
      revealed 2 main patterns: focal MET uptake in 12 and uniform global MET uptake in
      11 patients. Focal uptake corresponded to malignant glioma histology in 66.7%,
      and uniform global uptake to oligodendroglial histology in 72.7%. In
      oligodendrogliomas, global MET uptake constituted 81.5% (range 53.8-135%) of the
      MRI T(1) tumor volume on average and was limited to the MRI FLAIR tumor volume in
      86% (7/8) of patients. Tissue samples of focal MET uptake areas correlated with
      histological anaplasia in 66.6% (8/12 glioma patients), although 62.5% (5/8
      patients) lacked MRI contrast enhancement. CONCLUSION: MET PET image fusion may
      facilitate the targeting of anaplastic foci in homogeneous MRI non-enhancing
      gliomas for biopsy, may identify oligodendroglial histology preoperatively as
      well as characterize biologically active tumor volumes within MRI T(1)/FLAIR
      tumor areas of candidate patients for resection.

PMID- 18058644
TI  - Neuronavigation and resection of lesions located in eloquent brain areas under
      local anesthesia and neuropsychological-neurophysiological monitoring.
AB  - BACKGROUND: The aim of this study was to determine the safety and maximal
      extension of tumor resection achievable with a combination of awake craniotomy
      under local anesthesia, neuronavigation, and continuous neuropsychological and
      neurophysiological monitoring in patients with lesions within the eloquent brain.
      METHODS: We have performed 55 resections of different pathologies with
      neuronavigation on 52 patients from January 1998 to December 2002. Mean age was
      49 years, the male to female ratio was 37 to 15. All patients underwent a
      continuous examination by a neuropsychologist and repetitive cortical
      stimulations during the resection, and a 3-month postoperative neurological
      examination to determine functional outcome. Neurological outcome and results of
      resection of patients with gliomas were compared to a control group of 27
      patients with lesions in the central region who were operated under general
      anesthesia during the same time period. RESULTS: Tumor resection was stopped when
      a macroscopic total cytoreduction was achieved, or at the onset of neurological
      dysfunction. There was a higher rate of complete tumor resection (77% vs. 33%)
      and a lower rate of neurological deterioration (33% vs. 12%) in the study group
      compared to the control group. Overall, a complete resection in the study group
      was achieved in 40 patients (72%), a partial resection in 28%. Five patients
      developed a new deficit during surgery which resolved completely after a change
      of surgical strategy, 14 patients had a new deficit after surgery which improved
      within 3 months in 6 patients. There was no operative mortality. CONCLUSION: The
      combination of neuronavigation with cortical stimulation and repetitive
      neurological and language examinations allows a more radical resection of tumors
      in eloquent brain areas, otherwise considered as inoperable.

PMID- 18058645
TI  - Endoscopic treatment of hydrocephalus due to aneurysm of the vein of Galen: case
      report and literature review.
AB  - Aneurysms of the vein of Galen are uncommon vascular malformations. They are most
      frequently seen in infants and children, leading to heart failure and
      hydrocephalus. Exceptionally, they are detected in adults. Several theories have
      been proposed to explain hydrocephalus in these patients: obstruction of the
      cerebral aqueduct, impaired absorption of CSF after subarachnoid hemorrhage,
      passive ex-vacuo mechanism, or thrombosis of an aneurysm. Hydrocephalus has been
      treated mainly with cerebrospinal shunt procedures, but also direct surgery,
      radiosurgery and embolisation of the malformation have proved to be effective. We
      report the case of a partially thrombosed ectasia of the vein of Galen in a 44
      year-old male, with huge hydrocephalus successfully treated with an endoscopic
      third ventriculostomy.

PMID- 18058646
TI  - Cauda equina syndrome caused by primary lumbosacral and pelvic hydatid cyst: a
      case report.
AB  - INTRODUCTION: Hydatid disease occurs in humans as a result of faeco-oral
      contamination and spinal echinococcosis is rare even in areas where
      echinococcosis is endemic. Hydatid cyst primarily occurs in the liver and lungs.
      Bone involvement constitutes only 0.5-2% of all hydatidoses. About half of the
      bone involvement occurs in vertebrae. The thoracic spine is the most common site
      of the spinal hydatidosis. Primary hydatid cysts of the lumbar and sacral spinal
      canal are very rare. CASE REPORT: We present a 31-year-old man with cauda equina
      syndrome caused by a primary hydatid cyst of the lumbosacral and pelvic areas. He
      had been admitted to hospital with left foot and low back pain three years ago.
      Magnetic resonance imaging revealed an intraspinal hydatid cyst extending from L2
      to S2. The cyst had been totally removed. He was symptom-free for three years.
      After three years, he presented with acute cauda equina syndrome. His
      neurological examination revealed total plegia of dorsal flexion of the left foot
      and perianal hypoaesthesia. MRI showed lumbosacral and pelvic hydatidosis again.
      After total removal of the cyst, his neurological status revealed immediately
      relief. DISCUSSION: Hydatid cyst is an important health problem in some countries
      including Turkey. Bone involvement is seen in only 0.5-2% of cases. Furthermore
      sacral and lumber vertebral involvement is extremely rare. We presented a case
      with a spinal hydatid cyst which classified as a combination of intraspinal
      extradural, vertebral and paravertebral forms according to the Braitwate and Lees
      classification. Surgical excision and additional medical treatment is still the
      most effective treatment. Cysts located intraspinally have a tendency to rupture
      spontaneously. For this reason the high recurrence rate (30- 40%) is still a
      major problem in management.

PMID- 18058647
TI  - A case of intracranial hypoglossal neurinoma without hypoglossal nerve palsy:
      operative view of the preserved rostral trunk.
AB  - Hypoglossal neurinomas usually manifest with hemiatrophy and weakness of the
      tongue. A rare case of intracranial hypoglossal neurinoma without preoperative
      hypoglossal nerve dysfunction and its operative view are presented. A 36-year-old
      female who presented with headaches and vertigo was admitted to our hospital. The
      neurological examination revealed bilateral papilledema and mild truncal ataxia,
      although weakness and atrophy of the tongue were not observed. Magnetic resonance
      and computed tomography images demonstrated a large foramen magnum tumor without
      enlargement of the hypoglossal canal. Total removal of the tumor was performed
      via a lateral suboccipital craniotomy and C1 partial laminectomy. During the
      operation, two trunks were observed for the hypoglossal nerve at the entrance of
      the hypoglossal canal. The tumor arose from the caudal trunk, while the intact
      rostral trunk entered the hypoglossal canal normally. The tumor only developed
      intracranially, and since the rostral trunk of the hypoglossal nerve was intact,
      the patient did not present with hypoglossal nerve palsy preoperatively.

PMID- 18058648
TI  - Agenesis of the left internal carotid artery associated with right anterior
      cerebral artery A1 segment bifurcation aneurysm: a case report.
AB  - Agenesis of the internal carotid artery occurs in less than 0.01% of the
      population. Intracranial aneurysms accompany agenesis in 25-43% of the patients.
      We present a unique patient with a saccular aneurysm of the anterior
      communicating artery associated with agenesis of contralateral internal carotid
      artery.

PMID- 18058649
TI  - Transmuscular trocar technique - minimal access spine surgery for far lateral
      lumbar disc herniations.
AB  - OBJECTIVE: Minimal access spine surgery (MASS) is gaining increasing importance
      in microsurgery of the lumbar spine. From a current prospective series we present
      data on MASS for far lateral lumbar disc herniations (LLDH) via a transmuscular
      trocar technique (T(2)). The surgical procedure and operative results are
      demonstrated in detail. In contrast to conventional percutaneous endoscopic
      techniques, T(2) allows one to operate in the typical microsurgical fashion
      combined with the advantages of a minimal endoscopic approach with three
      dimensional visualization of the surgical target using the operating microscope.
      METHODS: Microsurgery was performed through a 1.6-cm skin incision with an 11.5
      mm diameter trocar that is obliquely inserted into the paraspinal muscles
      pointing at the lateral isthmus of the upper vertebral body. Fifteen patients
      were evaluated after a median follow-up period of 24 months. Overall outcome
      according to the modified MacNab criteria, effect of surgery on radicular pain
      and sensory or motor deficits, duration of surgery, complication rate, and
      duration of hospital stay were evaluated. RESULTS: Good to excellent clinical
      outcomes were achieved in 14/15 patients. Radicular pain and motor deficits
      improved in all patients postoperatively, while sensory deficits recovered in
      13/15 patients. The cosmetic results were excellent in all patients. No
      aggravation of symptoms after surgery was observed in any of the patients.
      CONCLUSIONS: The T(2) technique represents an auspicious alternative to standard
      open microsurgery for LLDH, which allows achievement of excellent clinical and
      cosmetic results, preservation of segmental spine stability, and avoidance of
      excessive soft tissue trauma.

PMID- 18058650
TI  - A simple technique for bridging small cranial dural defects without the use of
      grafts: technical note.
AB  - A watertight closure of the dura is important in preventing post-operative
      complications. Various techniques are described to close small dura defects. We
      present a simple technique that uses on site homologues dura tissue to bridge
      small dura defects by separating the periosteum from the inner meningeal layer.
      This provides a low-cost, tension-free repair without the use of synthetic
      materials or need to harvest autologous materials.

PMID- 18058651
TI  - No difference between supine and prone position for ERCP in conscious sedated
      patients: a prospective randomized study.
AB  - BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is
      usually performed with the patient prone or in the left lateral position. The
      supine position could be more comfortable and may facilitate airway management.
      On the other hand, technical difficulties and a greater risk of adverse
      cardiorespiratory events have been shown when ERCP is performed in a supine
      patient. Our aim was to assess, in a tertiary referral center, the differences
      between performing ERCP with the patient supine or prone, in terms of technical
      features and complications both during and after the procedure. PATIENTS AND
      METHODS: Between December 2005 and May 2006, 120 patients (66 female, mean age 62
      years) who had an intact papilla and were candidates for therapeutic ERCP were
      prospectively randomized to undergo ERCP under conscious sedation with midazolam,
      in the prone (n = 60) or supine (n = 60) position, by an expert endoscopist
      (tutor) or a trainee. The following parameters were recorded: difficulty of
      cannulation and difficulty of ECRP procedure, time needed to visualize the
      papilla, time needed to achieve opacification and cannulation, exam duration,
      episodes of tachy/bradycardia and desaturation, episodes of duodenoscope
      displacement into the stomach, and complications. RESULTS: Ninety-eight patients
      underwent ERCP for benign disease and 22 for malignant biliary strictures. The
      ERCP success rate was 98.3 % in the tutor group and 43.3 % in the trainee group.
      No significant differences were found between the two groups of operators (tutors
      and trainees) in the recorded parameters and complication rates encountered in
      prone versus supine patients. CONCLUSION: Our results show that ERCP success
      rates and complications (intraoperative and postoperative) are similar whether
      ERCP is performed with the patient prone or supine, even when operators are of
      differing skill levels. Training, technique, and a proper learning phase are
      recommended in order to perform ERCP with no differences whether the patient is
      prone or supine.

PMID- 18058652
TI  - Gastrointestinal telangiectasia: a study by EGD, colonoscopy, and capsule
      endoscopy in 75 patients.
AB  - BACKGROUND: The distribution of lesions in the gastrointestinal tract in patients
      with sporadic telangiectasia is at present unknown. PATIENTS AND METHODS: 75
      patients with sporadic telangiectasia underwent esophagogastroduodenoscopy (EGD),
      capsule endoscopy, and colonoscopy. Endoscopic diagnosis of telangiectasia and
      gastrointestinal bleeding were required for enrollment in the study. Hemorrhagic
      diathesis, co-morbidity, number of blood transfusions, and subsequent management
      were also noted. RESULTS: 35 of the patients presented with gastroduodenal
      vascular lesions, 51 with small-bowel lesions, and 28 with colonic lesions. 67 %
      of patients in whom EGD found telangiectasia also presented small-bowel vascular
      lesions at capsule endoscopy and 43 % colonic lesions at colonoscopy. 54 %
      percent of patients with positive colonoscopy also presented gastroduodenal
      lesions and 48 % small-bowel lesions. Patients with known duodenal lesions were
      more likely to have small-bowel lesions at capsule endoscopy (odds ratio [OR]
      10.19, 95 % CI 2.1 - 49.33, P = 0.003). Patients with associated diseases, such
      as liver cirrhosis, chronic renal failure, or heart valvulopathy, presented more
      severe disease requiring blood transfusions (OR 6.37, 95 % CI 1.39 - 29.2, P =
      0.015). The number of blood transfusions correlated with the number of sites
      affected ( R = 0.35, P = 0.002). The detection of new lesions at capsule
      endoscopy allowed new treatment in 46 % of patients. Mean follow-up was 18
      months. CONCLUSIONS: Sporadic telangiectasia is a multifocal disease potentially
      involving the whole digestive tract. Patients with duodenal telangiectasia show a
      higher risk of jejunal or ileal lesions. Capsule endoscopy is a useful diagnostic
      tool for the detection of such small-bowel vascular lesions, indicating a more
      specific prognosis and treatment strategy.

PMID- 18058653
TI  - Deep sedation for endoscopic retrograde cholangiopancreatography: intravenous
      propofol alone versus intravenous propofol with oral midazolam premedication.
AB  - BACKGROUND AND STUDY AIMS: The primary objective of the present study was to
      compare the dosage of intravenous propofol required in patients being sedated
      with propofol alone (group P) with the dosage of propofol required in patients
      who also received an oral dose of midazolam (group M + P) for endoscopic
      retrograde cholangiopancreatography (ERCP) procedures. The secondary objectives
      were to compare the two groups with regard to patient anxiety levels before the
      procedure, patient satisfaction, the recovery time, and the adverse events
      related to sedation. PATIENTS AND METHODS: A total of 91 consecutive patients
      undergoing ERCP were randomly assigned to one of the two medication regimens.
      Patients in group P (n = 45) received only intravenous propofol, titrated to
      achieve deep sedation. Patients in group M + P (n = 46) received 7.5 mg of
      midazolam orally 30 minutes before being given intravenous propofol, which was
      similarly titrated to achieve deep sedation. RESULTS: Patients receiving propofol
      alone required higher doses of propofol compared with those receiving synergistic
      sedation (512 +/- 238 mg vs. 330 +/- 223 mg respectively, P < 0.001). The
      patients' anxiety levels before the procedure were lower in group M + P patients
      than in group P patients (P < 0.001). The mean percentage decline in oxygen
      saturation during the procedure was significantly greater in group P patients
      than it was in group M + P patients. A significant drop in the oxygen saturation
      (to < 90 %) occurred in 11 group P patients and in three group M + P patients (P
      = 0.02). CONCLUSIONS: Our data suggest that synergistic sedation with an oral
      dose of midazolam combined with intravenous propofol can provide a significant
      benefit, with a reduction in the dosage of propofol required and in patient
      anxiety levels before ERCP.

PMID- 18058654
TI  - Diagnostic yield of capsule endoscopy in ulcerative colitis and inflammatory
      bowel disease of unclassified type (IBDU).
AB  - BACKGROUND AND STUDY AIMS: Capsule endoscopy is increasingly reported as an
      important diagnostic procedure in patients with known or suspected Crohn's
      disease, but its clinical utility in patients with ulcerative colitis or
      unclassified type inflammatory bowel disease (IBDU) is unclear. The aim of our
      study was to determine the diagnostic yield of capsule endoscopy for small-bowel
      disease in patients with ulcerative colitis and IBDU. PATIENTS AND METHODS: All
      data from patients with a history of ulcerative colitis or IBDU who underwent
      capsule endoscopy between October 2001 and August 2005 were analyzed for
      procedure indications and findings. Images were reviewed by an experienced
      capsule endoscopist. The finding of multiple ulcerations (three or more) on
      capsule endoscopy was classified as diagnostic of small-bowel Crohn's disease.
      RESULTS: 120 patients had undergone 122 capsule endoscopy procedures. Overall, 19
      of 120 patients (15.8 %) had capsule endoscopy findings consistent with the
      diagnosis of Crohn's disease. The proportion of patients with small-bowel disease
      was significantly higher among patients with a history of colectomy (7 of 21
      patients, 33 %) compared with those without colectomy (12/99, 12 %) ( P = 0.04).
      Among patients with positive findings on capsule endoscopy, 18 had also
      previously undergone a small-bowel follow-through study and only one showed
      findings consistent with Crohn's disease. CONCLUSIONS: Many patients with a
      diagnosis of ulcerative colitis and atypical features or IBDU may have small
      bowel findings on capsule endoscopy that are consistent with Crohn's disease.
      Capsule endoscopy should be considered in ulcerative colitis patients with
      atypical clinical features particularly after colectomy.

PMID- 18058655
TI  - Patchy villous atrophy in adult patients with suspected gluten-sensitive
      enteropathy: is a multiple duodenal biopsy strategy appropriate?
AB  - BACKGROUND AND STUDY AIMS: The current internationally accepted gold standard for
      diagnosing celiac disease is a small-bowel biopsy demonstrating villous atrophy.
      However, it has been suggested that the diagnosis might not be considered as
      confirmed if the villous atrophy is patchy. Our aim was to assess whether there
      is an optimal duodenal biopsy strategy for detecting villous atrophy in adult
      patients with suspected gluten-sensitive enteropathy. PATIENTS AND METHODS:
      Patients who had positive endomysial or tissue transglutaminase antibodies were
      prospectively recruited. Nine biopsies were taken from the duodenum: one from the
      duodenal bulb, four from the proximal duodenum, and four from the distal
      duodenum. Each biopsy was graded according to the Marsh criteria. All possible
      biopsy regimes were evaluated for their ability to detect the presence and
      severity of villous atrophy. RESULTS: A total of 56 patients were recruited (23
      men [41 %], 33 women [59 %]; mean age 47, range 16 - 85): 53/56 patients had
      villous atrophy present in at least one biopsy; 10/53 patients had biopsy
      specimens that showed "patchy" villous atrophy. In all 53 patients with villous
      atrophy this was detected by taking a minimum of three biopsies (sensitivity 100
      %, 95 % confidence interval [CI] 93.2 % - 100 %). However, this strategy always
      incorporated a duodenal bulb biopsy. The most severe degree of villous atrophy in
      all 56 patients was only detected by using a five-biopsy regime (sensitivity 100
      %, 95 % CI 93.6 % - 100 %). CONCLUSIONS: In this study we observed that villous
      atrophy in adult patients with suspected gluten-sensitive enteropathy (antibody
      positive) is patchy. For this reason we would suggest a minimum of three
      biopsies, incorporating a duodenal bulb biopsy, to ensure that villous atrophy is
      detected. However, a five-biopsy regime is required for recognition of the most
      severe lesion.

PMID- 18058656
TI  - Esophageal capsule endoscopy in patients with suspected esophageal disease:
      double blinded comparison with esophagogastroduodenoscopy and assessment of
      interobserver variability.
AB  - BACKGROUND AND STUDY AIMS: The study aim was to compare the diagnostic yield of
      capsule endoscopy and esophagogastroduodenoscopy (EGD) in patients with suspected
      esophageal disease. Secondary aims were to assess interobserver variability of
      capsule endoscopy readings and safety. PATIENTS AND METHODS: In total, 98
      patients (53 men, 53 +/- 13 years) with an indication for EGD were included. The
      patient population was artificially enriched to include two thirds of patients
      with abnormal esophageal findings at EGD, which was followed by capsule
      endoscopy. Capsule recordings were blindly read by three endoscopists, one from
      the center that recruited the patient and two from the other center. Study
      outcomes were the findings described on EGD and capsule endoscopy, agreement
      between EGD and capsule endoscopy for findings, quality of the capsule recording,
      and interobserver agreement for capsule endoscopy quality and findings. RESULTS:
      EGD was normal in 34 patients and showed esophageal findings in 62 (esophagitis
      28, hiatus hernia 21, varices 21, Barrett's esophagus 11, others 7). Average
      esophageal transit time of the capsule was 361 +/- 393 seconds. Capsule endoscopy
      was normal in 36 patients but detected esophagitis in 23, hiatus hernia in 0,
      varices in 23, Barrett's esophagus in 18, and others in 4. The positive
      predictive value of capsule endoscopy was 80.0 % and the negative predictive
      value was 61.1 %. Overall agreement per patient was moderate between EGD and
      capsule endoscopy for the per-patient (kappa = 0.42) and per-findings (kappa =
      0.40) analyses. Interobserver agreement between capsule endoscopy readings was
      moderate for findings (kappa = 0.39) and quality assessment (kappa = 0.24). No
      adverse event was observed after either EGD or capsule endoscopy. CONCLUSION: In
      this study, despite artificial prevalence enrichment, capsule endoscopy showed a
      moderate sensitivity and specificity in the detection of esophageal diseases.

PMID- 18058657
TI  - Colonoscopy, tumors, and inflammatory bowel disease.

PMID- 18058658
TI  - [Infection with Helicobacter pylori--outcome of a cross-sectional investigation].
AB  - BACKGROUND AND OBJECTIVE: Different information exists about the prevalence of
      Helicobacter pylori (Hp) in Germany, ranging from 35 to 40%. Several
      investigations have identified factors influencing the colonization of Hp in the
      stomach, but their significance is still being discussed. This study aimed at
      determining the prevalence of Hp in the metropolitan area of Hannover and
      defining the impact of education and lifestyle on Hp colonization. SUBJECTS AND
      METHODS: The study was designed as a cross-sectional survey. Advertisements were
      placed in newspapers and on the radio. Of 829 who responded and were informed of
      the study 35 were excluded according to predefined criteria, the remainder sent
      questionnaires and containers for stool samples. 579 persons returned
      questionnaires and stool samples, but 16 were excluded because of borderline test
      results. The detection of Hp was done with a test for Hp-antigens in stool (Femto
      Lab H. pylori-Cnx-Test, R-Biopharm). RESULTS: Among the final 563 tested persons
      (322 women, 241 men; mean age 46.6 12.2 years) 21% were Hp-positive and 79%
      negative. Participants with Hp were older than those without. Neither gender nor
      the consumption of caffeine, alcohol, nicotine and particular eating behaviour
      were related to Hp-status. However, persons who had incomplete or lower-level
      schooling were infected more often than those who had graduated from with high
      school. CONCLUSION: These results indicate that Hp-prevalence among German adults
      may be lower than previously published. Known associations between Hp infection
      and age and education were confirmed.

PMID- 18058659
TI  - [Cystic leak after laparoscopic cholecystectomy].

PMID- 18058660
TI  - [Adverse cutaneous drug reactions].

PMID- 18058661
TI  - [A rare cause of exertional dyspnea in a 63-year-old woman].
AB  - HISTORY AND CLINICAL FINDINGS: A 63-year-old woman was referred because of
      excertional dyspnea, pulmonary artery hypertension and right heart dilatation
      without evidence of pulmonary embolism. INVESTIGATIONS: Echocardiography,
      magnetic resonance tomography and right heart catheterisation revealed a left to
      right shunt through an sinus venosus defect and partial anomalous pulmonary
      venous return. DIAGNOSIS, TREATMENT AND COURSE: After surgical repair the
      hemodynamic changes normalized. The patient is doing well 12 weeks after surgery.
      CONCLUSION: Congenital heart disease should be considered as a rare cause of
      exertional dyspnea in the elderly. Before percutaneous interventional closure of
      atrial septal defects, concomitant anomalous partial pulmonary venous return
      should be ruled out.

PMID- 18058662
TI  - [Systems biology].

PMID- 18058663
TI  - [Nephrogenic systemic fibrosis--a new interdisciplinary challenge].
AB  - Nephrogenic systemic fibrosis (NSF) - previously termed nephrogenic fibrosis
      dermopathy - is a newly recognized disorder occurring only in patients with renal
      failure. Exposure to gadolinium-containing contrast agents used for magnetic
      resonance imaging has been associated with subsequent development of NSF. This
      disease is characterised by swelling and tightening of the skin, mostly at the
      limbs. In addition, internal organs may be involved, which may ultimately cause
      death in rare cases. Skin biopsy showing fibrous tissue and spindle cells
      positive for CD34, and factor XIIIa as well as CD68-positive macrophages confirms
      the diagnosis. The main therapeutic goal is restoration of renal function by
      renal transplantation or recovery from acute renal failure, whenever possible.
      There are few data regarding other measures. The best available evidence for some
      therapeutic effect relates to physiotherapy and extracorporal photopheresis.
      Gadodiamide and gadopentetate-dimeglumin must not be used in stage 4 and 5 renal
      failure. Other gadolinium-containing contrast media must be used with extreme
      caution in patients with advanced renal failure.

PMID- 18058664
TI  - [Intervening in the neural basis of one's personality: a practice-oriented
      ethical analysis of neuropharmacology and deep-brain stimulation].
AB  - Through the rapid progress in neuropharmacology it seems to become possible to
      effectively improve our cognitive capacities and emotional states by easily
      applicable means. Moreover, deep-brain stimulation may allow an effective
      therapeutic option for those neurological and psychiatric diseases which still
      can not be sufficiently treated by pharmacological measures. So far, however,
      both the benefit and the harm of these techniques are only insufficiently
      understood by neuroscience and detailed ethical analyses are still missing. In
      this article ethical criteria and most recent empirical evidence are
      systematically brought together for the first time. This analysis shows that it
      is irrelevant for an ethical evaluation whether a drug or a brain-machine
      interface is categorized as "enhancement" or "treatment" or whether it changes
      "human nature". The only decisive criteria are whether the intervention (1.)
      benefits the patient, (2.) does not harm the patient and (3.) is desired by the
      patient. However, current empirical data in both fields, neuropharmacology and
      deep-brain stimulation are still too sparse to adequately evaluate these
      criteria. Moreover, the focus in both fields has been strongly misled by
      neglecting the distinction between "benefit" and "efficacy": In past years
      research and clinical practice have only focused on physiological effects, but
      not on the actual benefit to the patient.

PMID- 18058666
TI  - [Peri-interventional antibiotic therapy for PEG-sites?].

PMID- 18058667
TI  - [Reconstruction of phalanx and metacarpal defects by autologous iliac crest
      transplants after tumour resection with joint involvement].
AB  - BACKGROUND: The reconstruction of large phalanx or metacarpal defects after
      tumour resection is still a challenge. In contrast to orthopaedic oncology there
      are no modular prostheses available in hand surgery. If the tumour affects the
      joint, often the only therapeutic option is an arthrodesis of the joint with a
      bone graft. In this study, a technique of joint reconstruction with an autologous
      bone graft from the iliac crest is presented. METHODS: Curative tumour resection
      is the main goal of the operation, including hemiresection of a finger joint if
      necessary. The bony defect is reconstructed with a bone graft from the iliac
      crest which is prepared to match the opposite joint surface as nearly as
      possible. An additional arthroplasty with the palmar plate might be performed.
      Postoperative care includes either 6 weeks transfixation of the affected joint
      with a K-wire or, if possible, early joint motion with a dynamic external
      fixateur. The operation technique and postoperative treatment are described;
      further the clinical and radiological follow-ups of three patients are shown and
      a review of the literature is given. RESULTS: The replacement of larger parts of
      the phalanx or metacarpal bone revealed good results with regard to joint
      movement of the partly replaced metacarpophangeal joint (MCP). Besides a good
      functional outcome patients were also nearly pain-free. Regarding the proximal
      interphalangeal (PIP) joint after resection of the middle phalanx, limited
      movement was found on the basis of a rapidly developing osteoarthritis, however,
      being accompanied by tolerable pain. CONCLUSION: The usage of autologous iliac
      crest transplants for reconstruction of metacarpal or phalanx defects which
      include one partner of the MCP joint can be advised after tumour resection,
      especially because of rare functional alternatives. Bone defects including one
      part of the PIP joint might also be replaced by iliac crest transplants. However,
      the functional outcome seems to be less attractive than in MCP reconstruction. In
      cases of development of osteoarthritis after iliac crest transplantation,
      arthroplasty with silicone spacers might be a salvage procedure to maintain joint
      movement.

PMID- 18058668
TI  - [Outcome assessment after reconstruction of complex defects of the forearm and
      hand with osteocutaneous free flaps].
AB  - PURPOSE: Complex defects of the forearm and hand often require microvascular
      reconstruction with composite osteocutaneous free flaps for limb salvage. Here, a
      postoperative outcome analysis of 15 patients is presented, who were treated by
      free composite tissue transplantation between 1992 and 2004 in a single
      institution. PATIENTS AND METHODS: The assessment focused on the range of motion,
      the pain and grip strength as well as on the patient's individual physical
      functioning and self perception, measured with the DASH questionnaire.
      Additionally complications, return to work and the donor site morbidity were
      documented. RESULTS: Reasons for the combined defects were trauma, infections or
      malignant tumors. The patients' average age was 38 years. The average osseous
      defect was 11.7 cm (range, 6 to 21 cm), all patients suffered from additional
      soft tissue defects. Microvascular osteoseptocutaneous fibula transplantations (n
      = 8), osteocutaneous scapular or parascapular flaps (n = 6) and osteocutaneous
      lateral arm flaps were performed for reconstruction. The mean hospitalisation
      time was 39.3 days (range, 18 - 73 d). All defects could be reconstructed in a
      one-step reconstructive procedure after sequential debridements or after radical
      tumour resection. Two patients developed a pseudarthrosis, one had to undergo an
      ablation procedure due to persistent infection; however, the flap was well
      perfused. Every patient had a markedly reduced hand function compared with the
      unaffected extremity, however the functional results were satisfactory with a
      mean DASH score of 25.3 (range, 0 to 42). This reflects only a moderate
      disability in activities of daily living. From the patients' point of view the
      functional results were more than acceptable when the potential alternatives were
      taken into consideration. This was also reflected by a high individual
      satisfaction. CONCLUSION: This retrospective analysis demonstrates that limb
      salvage with osteocutaneous free flaps is an important tool in the armamentarium
      for the treatment of composite defects in the forearm and hand. Functional
      results are good and the patient's high individual satisfaction justifies the use
      of these difficult reconstructive procedures.

PMID- 18058669
TI  - [Management of finger-level avulsion injuries].
AB  - BACKGROUND: In avulsion-type injuries of the fingers recovery of blood
      circulation is one of the major obstacles. The indication for finger
      reconstruction is discussed controversely, being influenced by the patient's
      needs, the degree of damage to the soft tissue and the prospects of success of
      the healing process. In this study we present our results after reconstruction of
      avulsion-type injuries of the fingers. Indications for finger reconstruction will
      be assessed in consideration of the expected outcome. PATIENTS AND METHODS: From
      1999 to 2006 we treated 18 patients with finger level avulsion injuries. 15
      casualties were caused by rings and three by ropes looped around a digit. The
      median age at injury was 23 (12 - 66) years. All patients were examined by an
      independent observer, who did not participate in the operation. Criteria were
      functional outcome and patient's complaints and satisfaction. Sensibility was
      evaluated by 2-point discrimination applying the Greulich star. Finger mobility
      was assessed with the Buck-Gramcko goniometer. RESULTS: According to the
      classification of Urbaniak as modified by Kay, 2 patients ranked in class II, 3
      in class III and 13 suffered from complete avulsion-amputations (class IV). Of
      the latter, 8 allowed primary reconstruction of the blood circulation. Two
      fingers required early or late secondary amputation. After finger reconstruction,
      patients spent a median time of 18 (12 - 32) days in hospital while primary
      amputation resulted in a shorter stay of 4 (2 - 5) days. Active motion after
      replantation in the proximal interphalangeal joint was reduced on average to 64
      (25 - 100) degrees. The distal interphalangeal joint nearly ankylosed in all
      patients following replantation except for one case with an active motion of 40
      degrees . Good sensibility could be achieved in one case, protective sensibility
      in three and none in two patients. All patients with preserved fingers would
      again decide in favour of finger replantation. CONCLUSION: In specialised centres
      replantation of complete avulsion-type finger amputations can be achieved. The
      decision for or against replantation should only be made after microsurgical
      assessment of the severed soft tissue and in consideration of the patient's
      specific demands. With the right indication for reconstruction, the patient's
      satisfaction often outweighs even poor functional outcomes.

PMID- 18058670
TI  - [Functional results after the Kapandji-Sauve operation for salvage of the distal
      radioulnar joint].
AB  - INTRODUCTION: The Kapandji-Sauve procedure is a salvage operation for the
      treatment of painful arthrosis of the distal radioulnar joint (DRUJ). It should
      be performed if an anatomical reconstruction of the DRUJ is not longer possible.
      The present study was designed to evaluate mid-term results by means of objective
      parameters (strength, range of motion, Krimmer and Mayo wrist scores) and
      subjective self-assessment of patient disabilities (DASH, pain) after the
      Kapandji-Sauve procedure. PATIENTS AND METHODS: Fifteen patients (8 female, 7
      male, average age 49 years) underwent Kapandji-Sauve procedure and were
      retrospectively reviewed 55 months after the operation (range, 6 months to 8
      years). As a reason for DRUJ arthrosis we found fractures of the distal radius in
      7 patients, severe contusion and distorsion trauma (5), luxation of the DRUJ (2)
      and a Madelung deformity (1). For evaluation of grip strength the Jamar
      dynamometer was used. Pain assessment was performed with a visual analogue scale
      (VAS 0 - 100) pre- and postoperatively, before and after physical load was used.
      The DASH questionnaire was used in all patients for subjective outcome
      assessment. RESULTS: Forearm rotation improved by 59,7 % (89,3 to 142,7 degrees)
      as well as grip strength by 63,6 % (13 to 20,7 kg) compared preoperative to
      postoperative. Pain reduction was significant (p = 0,003) before physical load by
      48,6 % and after physical load by 63,1 % compared with the preoperative values.
      The mean DASH score was 41,6 points, Krimmer and Mayo-Wrist scores were 61 and 63
      respectively. Radioulnar impingement occurred in 14 patients after an X-ray under
      load. Because of the improvement of forearm rotation and grip strength 12
      patients would undergo the procedure again, three patients were not satisfied
      with their results. CONCLUSION: Our clinical findings show good improvement of
      forearm rotation, grip strength and reduction of pain after Kapandji-Sauve
      procedure. However midrange DASH, Mayo and Krimmer-Wrist scores suggest that the
      Kapandji-Sauve procedure is not able to provide a solution for every complex, non
      reconstructable DRUJ disorder.

PMID- 18058671
TI  - [Soft-tissue defects on the dorsum of the hand by extravasation of the cytostatic
      agents: surgical options of treatment].
AB  - Systemic treatment with chemotherapeutic agents is often applied by infusions
      over peripheral vein cannulae located on the hands and lower arms. Dislocation of
      the cannulae or vein perforation causes an extravasation of the cytostatic agent.
      This complication occurs in approximately 0.1 - 6 % of intravenous treatments and
      is rarely noticed before administration of greater volumes. Depending on the
      tissue toxicity of the administered substances, the extravasation results in
      tissue damage of different extents. In a few cases, only conservative therapy is
      required. The majority of patients, however, needs immediate surgical therapy.
      The reason for this is the severe tissue damage caused by the chemotherapeutic
      agent that accumulates in the subcutaneous fat where it destroys the connective
      and fat tissue, nerves, vessels, tendons and muscles, impairing the functionality
      of the entire hand and arm. In very severe cases, partial or complete amputation
      of the extremity is the only treatment. The application of antidotes has been
      discussed controversially and is not a standard procedure. In the past 11 years,
      18 patients with extravasations of chemotherapeutics on the dorsum of the hand
      were admitted to our department. After radical debridement no primary closure of
      the resulting defect was advisable in the first operation. In all cases we could
      later perform a stable wound closure. In our opinion, this two-step procedure
      with primary radical debridement, temporary wound coverage and later wound
      closure should be performed regularly.

PMID- 18058672
TI  - Macrodystrophia lipomatosa: macrodactyly related to affected nerves, and a review
      of the literature.
AB  - Macrodystrophia lipomatosa (ML) is a rare disease causing congenital local
      gigantism of part of an extremity mostly through proliferation of fibro-adipose
      tissue. This study is one of few that specifically describe 8 ML patients with
      histological confirmation of the diagnosis combined with the 79 histologically
      confirmed cases already described in the literature. The goals of this study are
      to describe this malformation by using only histologically confirmed cases, to
      offer some insight on current opinions on ML by reviewing the histologically
      confirmed cases described in the literature, and to make the postulation of
      autonomic nerve dysfunction as the aetiology of ML more plausible.

PMID- 18058673
TI  - [Arrosion of flexor tendons after palmar plate osteosynthesis of the distal
      radius: three case reports].
AB  - Indication of palmar plate osteosynthesis of the distal radius has steadily
      broadened over recent years. The reason for this has been the introduction of
      angle stable implants. In addition, advantages were attributed to the palmar
      plate over the dorsal plate position on the distal radius through the covering of
      the M. pronator quadratus as a means of preventing the occurrence of arrosion of
      the tendon. Over a period of 12 months we treated 3 patients with varying degrees
      of flexor tendon rupture after palmar plate osteosynthesis, indicating that the
      incidence of flexor tendon arrosion occurring through palmar plate osteosynthesis
      is possibly greater than previously assumed.

PMID- 18058674
TI  - [Treatment of chronic recurrent synovial fistula following radiosynoviorthesis:
      two case reports].
AB  - Chronic recurrent synovial fistulae of the knee are uncommon. They can occur
      after traumatic injuries, as complication after surgical treatment or in patients
      with rheumatoid arthritis as spontaneous complication after trauma. No consensus
      exists about the adequate treatment and literature on this subject is scarce. Two
      cases are presented in which synovial fistula had occurred after
      radiosynoviorthesis. Previous conservative and conventional surgery failed to
      solve the problem as the fistulae remained chronic and recurrent. However both,
      radical debridement and plastic reconstruction by either a fasciocutaneous or a
      myocutaneous gastrocnemius flap were successful.

PMID- 18058675
TI  - [Neuropathy of the median nerve caused by intraneural haematoma after carpal
      tunnel release in an anticoagulated patient].
AB  - We report about the sudden onset of a median nerve neuropathy in an
      anticoagulated patient eight weeks after uneventful carpal tunnel release.
      Several differential diagnosis have to be considered: compression syndrome as
      well as iatrogenic damage of the median nerve due to the preliminary procedure or
      even concomitant disease can generate symptoms of peripheral neuropathy. We
      diagnosed an intraneural haematoma through surgical exploration. This rare
      complication of oral anticoagulation therapy occurred spontaneously and was
      treated successfully by interfascicular neurolysis.

PMID- 18058676
TI  - Chondroid syringoma of the hand: a rare localization.
AB  - Chondroid syringoma is a rare benign neoplasm of the sweat glands that usually
      occurs in the head and neck region. We describe a 18-year-old male patient with a
      benign chondroid syringoma that occurred at an unusual site, leading to
      compression symptoms of the ulnar nerve causing symptoms at the hypothenar region
      of the right hand. Although it is a rare tumor at an unusual site, it should be
      included in the differential diagnosis of the hand tumors.

PMID- 18058677
TI  - [New diagnostic concepts and tools for the dementias--so what?].

PMID- 18058678
TI  - [Neurosyphilis--diagnosis and treatment approaches in clinical psychiatry].

PMID- 18058679
TI  - [Are professional dental health care workers (dentists, dental technicians,
      assistants) in danger of noise induced hearing loss?].
AB  - BACKGROUND: Rotating instruments in dentistry are radiating an unpleasant high
      frequency noise, which was supposed to produce hearing loss by its loudness.
      Therefore frequently notifications and recognizing procedures were initiated
      because of the suspicion of occupational noise-induced hearing loss (German
      listing for occupational diseases as given by decree: Number 2301). In recent
      years dentists, dental technicians and dental assistants repeatedly had to be
      tested because of a suspicion for noise-induced inner ear damage. METHODS: Noise
      measurements were performed in 3 working places of dentists and 7 dental
      laboratories. RESULTS: In regard to dentists and dental assistants it was found
      that the aspirator, not the rotating instruments, was the most intense source for
      noise in the office. The averaged daily noise level was measured between 70 and
      77 db(A) and was therefore obviously below the inner ear damaging limit of 85
      dB(A). For dental technicians the on-site related averaged daily noise level was
      about 68 dB(A) and the person related averaged daily noise level was about 76
      dB(A). In some particular cases 80 dB(A) were exceeded, but relevant levels for
      an occupational noise trauma were not reached. It has to be taken into
      consideration that the rotating instruments got a considerable noise reduction in
      the last decade. Additionally it has to be taken into account for the calculation
      that the averaged running time of rotating instruments is 30 minutes per day in
      the office. Therefore, a notification or a recognizing procedure can regularly
      stand aside. CONCLUSION: An endangering by noise as given by the German
      occupational disease decree (more than 85 db(A)) cannot usually be expected for
      the dentist, the dental assistant and the dental technician.

PMID- 18058680
TI  - Cytotoxicity and p-glycoprotein modulating effects of quinolones and
      indoloquinazolines from the Chinese herb Evodia rutaecarpa.
AB  - The antimycobacterial quinolones 1-methyl-2-undecyl-4-quinolone,
      dihydroevocarpine and evocarpine as well as the indoloquinazoline alkaloids
      rutaecarpine and evodiamine - all from the Chinese medicinal herb Evodia
      rutaecarpa - were tested in two in vitro assays, for cytotoxicity and interaction
      with p-glycoprotein (p-gp). Cytotoxicity was measured in a cell proliferation
      assay against CCRF-CEM leukemia cells and their p-gp over-expressing subline
      CEM/ADR5000. An assay monitoring the p-gp-dependent accumulation of the dye
      calcein in porcine brain capillary endothelial cells (PBCECs) was used to study
      interactions of the test substances with this efflux pump. Rutaecarpine and
      evodiamine showed quite high toxicity with IC (50) values from 2.64 to 4.53
      microM and were weak modulators of p-gp activity. The degrees of resistance in
      CEM/ADR5000 towards the saturated quinolones 1-methyl-2-undecyl-4-quinolone and
      dihydroevocarpine were between 3 and 4. In the calcein assay, these two
      quinolones were shown to be moderate modulators of p-gp activity. Evocarpine, on
      the other side, is not transported by p-gp, and showed only slight toxicity at
      the highest test concentration of 30 microM.

PMID- 18058681
TI  - Towards unity for health in the Barceloneta: an innovative experience in
      community-based primary health care.
AB  - CONTEXT: This paper describes a unique experience in community-based primary care
      in the Barceloneta, an economically deprived neighbourhood in Barcelona, Spain.
      The paper analyzes the reasons for the successes and failures of the project in
      light of TUFH principles. METHODS: The Primary Care Team (PCT) that staffed and
      ran the Health Centre in the Barceloneta facilitated the active participation of
      entities and individuals from the neighbourhood in deciding questions of care
      provision and resource allocation. They also collaborated with other service
      providers in the neighbourhood including pharmacists, with whom the PCT developed
      a program for monitoring diabetic and hypertensive patients in the local
      pharmacies. RESULTS: The health centre registered some of the best outcomes in
      Barcelona, including: time spent with each patient; capacity for the physicians
      to resolve patient visits without a referral; and patient satisfaction. Outcomes
      for patients followed by their local pharmacists were equivalent to those seen in
      the clinic, with lower costs. Despite these impressive results, conflicts among
      and between various stakeholders led to the project's termination. CONCLUSIONS:
      Innovations in any system can lead to conflicts of interest between stakeholders,
      derailing even demonstrably effective programs. A stable partnership with other
      stakeholders, particularly the community and health care administrators, in this
      case, is key. However, the community is not monolithic, and efforts must be made
      to ensure that other stakeholders do not widen intercommunity disputes. Effective
      dissemination of information on the impact of the project on the population is
      important to maintain relationships with the various stakeholders.

PMID- 18058682
TI  - [Neighbourhood rural medicine: an experience of rural doctors in Mali].
AB  - The main constraint to improving access to health services of quality in rural
      areas is to attract qualified health personnel in these areas. A fifteen years
      experience in rural health in Mali has shown that it is possible to develop
      community medicine practices in an African context that do integrate individual
      care and public health activities. The policy of decentralization of health
      services encouraged local communities and municipalities to recruit rural doctors
      themselves. An initiative of rural doctors materialized with this event as they
      founded a national association and adhere to the principles of a Charter to
      provide quality health care at an affordable cost. A mechanism of quality
      improvement was established with the participation of several partners: a
      professional association, a funding non-governmental organization, and groups of
      academic staff and health managers. This paper describes the evolution of the
      rural doctors' experience, its philosophy, conditions that made it successful,
      constraints it had to overcome and the attitude of partners. It highlights the
      potential of health care personnel in Africa to provide primary health care well
      beyond traditional programs on prevalent diseases and to respond to both urgent
      individual needs and pressing public health requirements.

PMID- 18058683
TI  - Towards unity for health: lessons for health development in Canada.
AB  - INTRODUCTION: The Sherbrooke-Estrie integrated cardiovascular health program
      (SEICHP) was developed in the Canadian province of Quebec. It was among the 12
      field projects selected in 2001 around the world by the World Health Organization
      (WHO) to implement the TUFH (Towards Unity for Health) strategy as a way to
      improve health development responding to people's needs through integration of
      health services and partnership among key stakeholders. SEICHP tailored and
      applied the TUFH approach. It developed comprehensive and integrated services for
      people suffering or being at risk of cardiovascular problems in its region of
      influence. It emphasized complementarity, efficiency of resource use,
      interprofessional collaboration and partnership. In this, SEICHP complied with
      TUFH criteria. Information on how it adapted and applied these with relative
      success is reported. LESSONS FOR HEALTH DEVELOPMENT: Even though difficulties in
      evaluation represent a limitation, major lessons learned linked to TUFH criteria
      include: the necessity to involve the public health and individual health people
      at all phases of program development and implementation, including the
      identification of information to be collected; an emphasis on integration brings
      health professionals to realize the importance of interdisciplinary work and
      academic institutions to modify their educational programs; restraining and
      supporting factors to partnership must be considered purposefully to optimize the
      partnership process; and optimal assessment of impact is difficult to attain.
      CONCLUSION: TUFH gave SEICHP a comprehensive conceptual framework for health
      development to work with. It had a highly significant impact on its development
      and provides direction for its future actions.

PMID- 18058684
TI  - Population health and public health training for Australian rural general
      practice registrars: a six year program 2000-2006.
AB  - BACKGROUND: In Australia, population health and public health are core aspects of
      postgraduate general practice training. AIMS: This paper describes an academic
      general practice training post in population health and public health for rural
      GP registrars in North Western New South Wales. Furthermore, this paper describes
      how this training post incorporates the principles of "Towards Unity for Health".
      METHODS: In 2000, a collaborative reference group of local and national
      organisations advised on curriculum development. During training, GP registrars
      conduct a research project applying population health and public health
      principles in a rural community. Content and thematic analyses of research
      documents and GP registrar evaluations were used to provide examples of how this
      training post incorporates principles of "Towards Unity for Health". RESULTS: The
      posts have been evaluated and were viewed favourably by registrars, local and
      national organisations. Six GP registrars have been recruited to undertake this
      training post since 2001. Their research projects include: smoking cessation,
      childhood obesity and hepatitis C. After completing this form of training, two
      registrars have become involved in medical education and three have remained to
      work in the region. The educational model developed in this project has
      similarities with "Toward Unity for Health" with partnerships developed between
      academic institutions and health managers. DISCUSSION: This paper presents a
      feasible model to train GP registrars in population health and public health
      skills in a rural region. Further research is required to assess the
      applicability of this model to other regions of Australia and internationally.

PMID- 18058685
TI  - Lessons from a local government unit - health academic partnership.
AB  - CONTEXT: The devolution of health services from the Department of Health to the
      Local Government Unit in the Philippines in 1992 led to the deterioration of the
      management of local health services. The UP College of Medicine (UPCM) has forged
      a partnership with a Local Government Unit of a rural municipality to implement a
      community based health program geared towards the development of local health
      systems. OBJECTIVE: Program objectives were: (1) to provide learning
      opportunities for UPCM faculty, medical residents and students in community
      medicine; and (2) to assist communities develop their health systems.
      INTERVENTIONS: In July, 2004, the UPCM jointly drafted a municipal health plan
      with its partner municipality. Before the actual planning session, the rural
      health midwives were assisted by the UPCM students in determining the health
      needs of their communities and in drafting community health plans. The plans were
      then presented by the midwives in a 2-day planning workshop, and became the basis
      of the municipal health plan. MAIN OUTCOMES: The outcome of the workshop was the
      first municipal health plan that this health office had drafted. Main outcomes
      from the implementation of the plan included the organization of the Local Health
      Board, improved health service provision by the municipal health office, active
      health committees in selected villages and better learning opportunities for
      medical residents and interns. CONCLUSION: Colleges of Medicine in the
      Philippines can and should play a role in the development of local health systems
      within the overall framework of Alma Ata Primary Health Care. National health
      planners should seriously consider this role of the health academe.

PMID- 18058686
TI  - An innovative partnership to address breast cancer screening among vulnerable
      populations.
AB  - CONTEXT: Breast cancer is the most common non-skin malignancy among U.S. women.
      Vulnerable populations such as low-income women, racial/ethnic minorities, and
      the uninsured have lower rates of screening mammography use and bear a
      disproportionate burden of disease. OBJECTIVES: The Breast Cancer Education
      Project (BCEP) was created to address the needs of medically underserved women in
      Cook County through high-quality breast cancer screening, education and support.
      The BCEP also provides a service-learning opportunity in which medical students
      can provide a valuable health service while obtaining important skills that
      enable them to work more effectively within medically underserved communities.
      CONCLUSION: The BCEP is an innovative collaboration between academic medical
      centers, safety-net health systems, community-based organizations and public
      health organizations. It represents a model for addressing issues of disparate
      access to breast cancer screening within vulnerable communities that contribute
      to higher breast cancer mortality.

PMID- 18058687
TI  - Creating and testing the concept of an academic NGO for enhancing health equity:
      a new mode of knowledge production?
AB  - CONTEXT: Collaborative action is required to address persistent and systematic
      health inequities which exist for most diseases in most countries of the world.
      OBJECTIVES: The Academic NGO initiative (ACANGO) described in this paper was set
      up as a focused network giving priority to twinned partnerships between Academic
      research centres and community-based NGOs. ACANGO aims to capture the strengths
      of both in order to build consensus among stakeholders, engage the community,
      focus on leadership training, shared management and resource development and
      deployment. METHODS: A conceptual model was developed through a series of
      community consultations. This model was tested with four academic-community
      challenge projects based in Kenya, Canada, Thailand and Rwanda and an online
      forum and coordinating hub based at the University of Ottawa. FINDINGS: Between
      February 2005 and February 2007, each of the four challenge projects was able to
      show specific outputs, outcomes and impacts related to enhancing health equity
      through the relevant production and application of knowledge. CONCLUSIONS: The
      ACANGO initiative model and network has demonstrated success in enhancing the
      production and use of knowledge in program design and implementation for
      vulnerable populations.

PMID- 18058688
TI  - Promoting unity of purpose in district health service delivery in Uganda through
      partnerships, trust building and evidence-based decision-making.
AB  - CONTEXT: The Uganda Program for Human and Holistic Development (UPHOLD), a USAID
      funded project which supports health services in 34 Ugandan districts, was
      conceived at a time when promising interventions could not be expanded due to
      fragmented systems. This paper focuses on how the program addressed fragmentation
      to improve service delivery in the health sector. APPROACH: UPHOLD achieved
      results by utilizing grants and technical support to strengthen capacity in a
      decentralized setting to foster institutional behavior change, promote
      strengthened partnerships among stakeholders in health, and produce increased
      transparency and accountability. In addition, the Lot Quality Assurance Sampling
      (LQAS) survey methodology was institutionalized to promote a culture of evidence
      based decision-making at the district level. RESULTS: Evidence-based decision
      making and partnership-oriented implementation led to programmatic results and
      institutional behavior change in districts through synergetic relationships
      between local governments and Civil Society Organizations. The use of Insecticide
      Treated Nets increased from 11.2% in 2004 to 17.2% in 2005, clients utilizing
      HIV/AIDS counselling and testing services increased from 6,205 in 2004 to 85 947
      in 2005 and using Lot Quality Assurance Sampling methodology has begun to
      positively influence district and national staff mind sets leading to more
      evidence-based planning and decision-making. CONCLUSION: The pillars of 'evidence
      based decision-making' and 'partnerships', together with approaches which
      strengthen existing synergies, produced more results, faster. Programs designed
      to work with fragmented settings should consider using the same pillars and
      blocks to ultimately make a difference in the lives of program beneficiaries.

PMID- 18058689
TI  - Towards unity for health: time to think systems.

PMID- 18058690
TI  - Project to policy: TUFH principles in action in Australia.
AB  - CONTEXT: In 1999, Towards Unity For Health developed principles for patient-based
      health systems which included partnerships, raising the level of partnerships,
      integration of individual, population and public health, information management
      and measurement of outcomes. OBJECTIVE: To address the health workforce crisis in
      an area of remote north western New South Wales (NSW) in Australia. METHOD: The
      NSW Rural Doctors Network applied the TUFH principles in overcoming much of the
      crisis and developing an ongoing local health system which has answered many of
      the local needs. CONCLUSION: The project provided experience for policy change
      and development at both State and National levels.

PMID- 18058691
TI  - Controlling diseases, securing access to health care, strengthening health
      systems...squaring the circle?

PMID- 18058692
TI  - Towards unity for health utilising community-oriented primary care in education
      and practice.
AB  - CONTEXT: Although the evidence is overwhelming that healthcare is delivered more
      effectively if one involves the targeted communities in decisions concerning
      their health, top-down programs still rule the world. OBJECTIVES: In order to
      highlight the benefits of a community-oriented approach, we report the
      experiences from Ghent, Belgium on COPC styled healthcare initiatives and COPC
      modelled multidisciplinary education. Community-oriented Primary Care and
      Education: COPC is a five-step model combining primary health care, public health
      and community data and resources. The involvement of community (members) is a
      crucial element in any effort to effectively enhance health (care) in a given
      community. Small scale examples from two health centers are given. In order to
      train future healthcare workers to be able to function with the communities, they
      participate in a one-week interdisciplinary course based on the COPC cycle at the
      University of Ghent. The COPC program in relation to Its practical organisation,
      goals and limitations are presented and discussed. CONCLUSION: In order to reach
      health objectives set out by disease-specific or health promotion programs, a
      community-sensitive approach is needed, especially for the most deprived
      communities. The COPC model offers inspiration and can be a practical tool to
      work with communities. It is also feasible to create a short COPC exercise to
      prepare future healthcare workers for complex community work. This model is one
      of the ways to concretise some of the main objectives of TUFH.

PMID- 18058693
TI  - The challenge of improving health and medical care through undergraduate medical
      education "PRO-SAUDE".

PMID- 18058694
TI  - [The society "Sante en Francais": a successful Canadian model for partnership].
AB  - Francophone Canadians living in a context where French is a minority language
      have poor access to health services in their native language. To remedy this
      situation, the Canadian Government has adopted a networking model inspired from
      the strategy "Towards Unity For Health" (TUFH) elaborated by the World Health
      Organization (WHO). This model, used since 2001, has given rise to a large number
      of partnership networks covering the entire regions where minority Francophones
      live. In this model five key stakeholders in health are being involved: health
      professionals, communities, managers of health care institutions, educational
      institutions and governments. The Canadian Federal Government, in close
      collaboration with communities, directed the project through two non-for-profit
      agencies: the Societe Sante en Francais (SSF) and the Consortium National de
      Formation en Sante (CNFS), sharing a common vision and aiming at improving access
      to health services and hence health status of minority Francophones. The
      networking following the TUFH model created a lot of opportunities as well as
      many challenges to overcome.

PMID- 18058695
TI  - Towards unity for health: integrating purpose and action - the story of Estelita.

PMID- 18058696
TI  - Community-action councils: a pathway to embrace towards unity for health (TUFH).

PMID- 18058697
TI  - The search for HR in the new WHO director general inaugural message.

PMID- 18058698
TI  - Towards unity for health: the quest for evidence.

PMID- 18058700
TI  - [Towards Unity for Health" criteria applied to medical centers in Belgium].
AB  - OBJECTIVE: To describe the Belgian medical centers' experience against TUFH
      criteria. To identify convergences, strengths and weaknesses, and suggest
      explanations. To present current dynamics in medical centers. METHOD: Literature
      review on legislation, history, mode of operations and evaluations. OUTCOMES: The
      convergence of the Belgian medical centers' experience with TUFH criteria is
      striking, particularly regarding the use of a reference population and territory
      and the use of health information. Capitation fee encourages health personnel to
      change attitudes. The Belgian federation of medical centers should play a greater
      role in the education of health personnel. Partnership is widely practised.
      Impact measurements are favourable but should be generalized. CONCLUSION: The
      convergence between the TUFH approach and the one used by the Belgian medical
      centers, particularly in their integrated health centers has been demonstrated by
      use of TUFH criteria. While still a small fraction in the spectrum of health
      services in Belgium, though in steady progress, it is believed that integrated
      health centers should remain places for experiment on health care to help the
      entire system to reform.

PMID- 18058701
TI  - Genome-wide partial correlation analysis of Escherichia coli microarray data.
AB  - Transcriptional control is an essential regulatory mechanism employed by
      bacteria. Much about transcriptional regulation remains to be discovered, even
      for the most widely studied bacterium, Escherichia coli. In the present study, we
      made a genome-wide low-order partial correlation analysis of E. coli microarray
      data with the purpose of recovering regulatory interactions from transcriptome
      data. As a result, we produced whole genome transcription factor regulation and
      co-regulation graphs using the predicted interactions, and we demonstrated how
      they can be used to investigate regulation and biological function. We concluded
      that partial correlation analysis can be employed as a method to predict putative
      regulatory interactions from expression data, as a complementary approach to
      transcription factor binding site tools and other tools designed to detect co
      regulated genes.

PMID- 18058702
TI  - Optimal clone identifier for genomic shotgun libraries: "OC Identifier tool".
AB  - In DNA microarray experiments, the gene fragments that are spotted on the slides
      are usually obtained by the synthesis of specific oligonucleotides that are able
      to amplify genes through PCR. Shotgun library sequences are an alternative to
      synthesis of primers for the study of each gene in the genome. The possibility of
      putting thousands of gene sequences into a single slide allows the use of shotgun
      clones in order to proceed with microarray analysis without a completely
      sequenced genome. We developed an OC Identifier tool (optimal clone identifier
      for genomic shotgun libraries) for the identification of unique genes in shotgun
      libraries based on a partially sequenced genome; this allows simultaneous use of
      clones in projects such as transcriptome and phylogeny studies, using comparative
      genomic hybridization and genome assembly. The OC Identifier tool allows
      comparative genome analysis, biological databases, query language in relational
      databases, and provides bioinformatics tools to identify clones that contain
      unique genes as alternatives to primer synthesis. The OC Identifier allows
      analysis of clones during the sequencing phase, making it possible to select
      genes of interest for construction of a DNA microarray.

PMID- 18058703
TI  - Effects of sample re-sequencing and trimming on the quality and size of assembled
      consensus sequences.
AB  - The production of nucleic acid sequences by automatic DNA sequencer machines is
      always associated with some base-calling errors. In order to produce a high
      quality DNA sequence from a molecule of interest, researchers normally sequence
      the same sample many times. Considering base-calling errors as rare events, re
      sequencing the same molecule and assembling the reads produced are frequently
      thought to be a good way to generate reliable sequences. However, a relevant
      question on this issue is: how many times the sample needs to be re-sequenced to
      minimize costs and achieve a high-fidelity sequence? We examined how both the
      number of re-sequenced reads and PHRED trimming parameters affect the accuracy
      and size of final consensus sequences. Hundreds of single-pool reaction pUC18
      reads were generated and assembled into consensus sequences with CAP3 software.
      Using local alignment against the published pUC18 cloning vector sequence, the
      position and number of errors in the consensus were identified and stored in
      MySQL databases. Stringent PHRED trimming parameters proved to be efficient for
      the reduction of errors; however, this procedure also decreased consensus size.
      Moreover, re-sequencing did not have a clear effect on the removal of consensus
      errors, although it was able to slightly increase consensus.

PMID- 18058704
TI  - Intraflagellar transport complex in Leishmania spp. In silico genome-wide
      screening and annotation of gene function.
AB  - Flagella are constructed and maintained through the highly conserved process of
      intraflagellar transport (IFT), which is a rapid movement of particles along the
      axonemal microtubules of cilia/flagella. Particles that are transported by IFT
      are composed of several protein subunits comprising two complexes (A and B),
      which are conserved among green algae, nematodes, and vertebrates. To determine
      whether or not homologues to members of the IFT complex proteins are conserved in
      Leishmania spp, we scanned genomes, transcriptomes and proteomes of Leishmania
      species in a search for putative IFT factors, which were then identified in
      silico, compared, cataloged, and characterized. Since a large proportion of newly
      identified genes in L. major remain unclassified, with many of these being
      potentially Leishmania- (or kinetoplastid-) specific, there is a need for
      detailed analyses of homologs/orthologs that could help us understand the
      functional assignment of these gene products. We used a combination of integrated
      bioinformatics tools in a pathogenomics approach to contribute to the annotation
      of Leishmania genomes, particularly regarding flagellar genes and their roles in
      pathogenesis. This resulted in the formal in silico identification of eight of
      these homologs in Leishmania (IFT subunits, 20, 27, 46, 52, 57, 88, 140, and
      172), along with others (IFTs 71, 74/72, and 81), as well as sequence comparisons
      and structural predictions. IFT, an important flagellar pathway in Leishmania,
      begins to be revealed through screening of trypanosomatid genomes; this
      information could also be used to better understand fundamental processes in
      Leishmania, such as motility and pathogenesis.

PMID- 18058705
TI  - On the characterization of energy networks of proteins.
AB  - The construction of a realistic theoretical model of proteins is determinant for
      improving the computational simulations of their structural and functional
      aspects. Modeling proteins as a network of non-covalent connections between the
      atoms of amino acid residues has shown valuable insights into these
      macromolecules. The energy-related properties of protein structures are known to
      be very important in molecular dynamics. However, these same properties have been
      neglected when the protein structures are modeled as networks of atoms and amino
      acid residues. A new approach for the construction of protein models based on a
      network of atoms is presented. This method, based on interatomic interaction,
      takes into account the energy and geometric aspects of the protein structures
      that were not employed before, such as atomic occlusion inside the protein, the
      use of solvation, protein modeling and analysis, and the use of energy potentials
      to estimate the energies of interatomic non-covalent contacts. As a result, we
      achieved a more realistic network model of proteins. This model has the virtue of
      being more robust in face of different unknown variables that usually are
      arbitrarily estimated. We were able to determine the most connected residues of
      all the proteins studied, so that we are now in a better condition to study their
      structural role.

PMID- 18058706
TI  - A framework for modeling of juxtacrine signaling systems.
AB  - Juxtacrine signaling is intercellular communication, in which the receptor of the
      signal (typically a protein) as well as the ligand (also typically a protein,
      responsible for the activation of the receptor) are anchored in the plasma
      membranes, so that in this type of signaling the activation of the receptor
      depends on direct contact between the membranes of the cells involved. Juxtacrine
      signaling is present in many important cellular events of several organisms,
      especially in the development process. We propose a generic formal model (a
      modeling framework) for juxtacrine signaling systems that is a class of discrete
      dynamic systems. It possesses desirable characteristics in a good modeling
      framework, such as: a) structural similarity with biological models, b) capacity
      of operating in different scales of time, and c) capacity of explicitly treating
      both the events and molecular elements that occur in the membrane, and those that
      occur in the intracellular environment and that are involved in the juxtacrine
      signaling process. We have implemented this framework and used it to develop a
      new three-level discrete model for the neurogenic network and its participation
      in neuroblast segregation. This paper presents the details of this framework and
      its current status.

PMID- 18058707
TI  - Proteinase inhibition using small Bowman-Birk-type structures.
AB  - Bowman-Birk inhibitors (BBIs) are cysteine-rich and highly cross-linked small
      proteins that function as specific pseudosubstrates for digestive proteinases.
      They typically display a "double-headed" structure containing an independent
      proteinase-binding loop that can bind and inhibit trypsin, chymotrypsin and
      elastase. In the present study, we used computational biology to study the
      structural characteristics and dynamics of the inhibition mechanism of the small
      BBI loop expressing a 35-amino acid polypeptide (ChyTB2 inhibitor) which has
      coding region for the mutated chymotrypsin-inhibitory site of the soybean BBI. We
      found that in the BBI-trypsin inhibition complex, the most important interactions
      are salt bridges and hydrogen bonds, whereas in the BBI-chymotrypsin inhibition
      complex, the most important interactions are hydrophobic. At the same time,
      ChyTB2 mutant structure maintained the individual functional domain structure and
      excellent binding/inhibiting capacities for trypsin and chymotrypsin at the same
      time. These results were confirmed by enzyme-linked immunosorbend assay
      experiments. The results showed that modeling combined with molecular dynamics is
      an efficient method to describe, predict and then obtain new proteinase
      inhibitors. For such study, however, it is necessary to start from the sequence
      and structure of the mutant interacting relatively strongly with both trypsin and
      chymotrypsin for designing the small BBI-type inhibitor against proteinases.

PMID- 18058708
TI  - miRNApath: a database of miRNAs, target genes and metabolic pathways.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression
      and hence play important roles in metabolic pathways. Recent studies have
      evidenced the interrelation of miRNAs with cell proliferation, differentiation,
      development, and diseases. Since they are involved in gene regulation, they are
      intrinsically related to metabolic pathways. This leads to questions that are
      particularly interesting for investigating medical and laboratorial applications.
      We developed an miRNApath online database that uses miRNA target genes to link
      miRNAs to metabolic pathways. Currently, databases about miRNA target genes
      (DIANA miRGen), genomic maps (miRNAMap) and sequences (miRBase) do not provide
      such correlations. Additionally, miRNApath offers five search services and a
      download area. For each search, there is a specific type of input, which can be a
      list of target genes, miRNAs, or metabolic pathways, which results in different
      views, depending upon the input data, concerning relationships between the target
      genes, miRNAs and metabolic pathways. There are also internal links that lead to
      a deeper analysis and cross-links to other databases with more detailed
      information. miRNApath is being continually updated and is available at
      http://lgmb.fmrp.usp.br/mirnapath.

PMID- 18058709
TI  - Abundance and diversity of resistance genes in the sugarcane transcriptome
      revealed by in silico analysis.
AB  - Resistance genes (R-genes) are responsible for the first interaction of the plant
      with pathogens being responsible for the activation (or not) of the defense
      response. Despite their importance and abundance, no tools for their automatic
      annotation are available yet. The present study analyzed R-genes in the sugarcane
      expressed sequence tags database which includes 26 libraries of different tissues
      and development stages comprising 237,954 expressed sequence tags. A new
      annotation routine was used in order to avoid redundancies and overestimation of
      R-gene number, common mistakes in previous evaluations. After in silico
      screening, 280 R-genes were identified, with 196 bearing the complete domains
      expected. Regarding the alignments, most of the sugarcane's clusters yielded best
      matches with proteins from Oryza sativa, probably due to the prevalence of
      sequences of this monocot in data banks. All R-gene classes were found except the
      subclass LRR-NBS-TIR (leucine-rich repeats, nucleotide-binding site, including
      Toll interleukin-1 receptors), with prevalence of the kinase (Pto-like) class. R
      genes were expressed in all libraries, but flowers, transition root to shoot, and
      roots were the most representative, suggesting that in sugarcane the expression
      of R-genes in non-induced conditions prevails in these tissues. In leaves, only
      low level of expression was found for some gene classes, while others were
      completely absent. A high allelic diversity was found in all classes of R-genes,
      sometimes showing best alignments with dicotyledons, despite the great number of
      genes from rice, maize and other grasses deposited in data banks. The results and
      future possibilities regarding R-genes in sugarcane research and breeding are
      further discussed.

PMID- 18058710
TI  - Application of MUTIC to the exploration of gene expression data in prostate
      cancer.
AB  - We show here an example of the application of a novel method, MUTIC (model
      utilization-based clustering), used for identifying complex interactions between
      genes or gene categories based on gene expression data. The method deals with
      binary categorical data which consist of a set of gene expression profiles
      divided into two biologically meaningful categories. It does not require data
      from multiple time points. Gene expression profiles are represented by feature
      vectors whose component features are either gene expression values, or averaged
      expression values corresponding to gene ontology or protein information resource
      categories. A supervised learning algorithm (genetic programming) is used to
      learn an ensemble of classification models distinguishing the two categories
      based on the feature vectors corresponding to their members. Each feature is
      associated with a "model utilization vector", which has an entry for each high
      quality classification model found, indicating whether or not the feature was
      used in that model. These utilization vectors are then clustered using a variant
      of hierarchical clustering called Omniclust. The result is a set of model
      utilization-based clusters, in which features are gathered together if they are
      often considered together by classification models - which may be because they
      are co-expressed, or may be for subtler reasons involving multi-gene
      interactions. The MUTIC method is illustrated here by applying it to a dataset
      regarding gene expression in prostate cancer and control samples. Compared to
      traditional expression-based clustering, MUTIC yields clusters that have higher
      mathematical quality (in the sense of homogeneity and separation) and that also
      yield novel insights into the underlying biological processes.

PMID- 18058711
TI  - Ab initio 3-D structure prediction of an artificially designed three-alpha-helix
      bundle via all-atom molecular dynamics simulations.
AB  - The rate at which knowledge about genomic sequences and their protein products is
      produced is increasing much faster than the rate of 3-dimensional protein
      structure determination by experimental methods, such as X-ray diffraction and
      nuclear magnetic resonance. One of the major challenges in structural
      bioinformatics is the conversion of genomic sequences into useful information,
      such as characterization of protein structure and function. Using molecular
      dynamics (MD) simulations, we predicted the 3-dimensional structure of an
      artificially designed three- alpha -helix bundle, called A3, from a fully
      extended initial conformation, based on its amino acid sequence. The MD protocol
      enabled us to obtain the secondary, in 1.0 ns, as well as the supersecondary and
      tertiary structures, in 4.0-10.0 ns, of A3, much faster than previously described
      for a similar protein system. The structure obtained at the end of the 10.0-ns MD
      simulation was topologically a three-alpha-helix bundle.

PMID- 18058712
TI  - Sting_RDB: a relational database of structural parameters for protein analysis
      with support for data warehousing and data mining.
AB  - An effective strategy for managing protein databases is to provide mechanisms to
      transform raw data into consistent, accurate and reliable information. Such
      mechanisms will greatly reduce operational inefficiencies and improve one's
      ability to better handle scientific objectives and interpret the research
      results. To achieve this challenging goal for the STING project, we introduce
      Sting_RDB, a relational database of structural parameters for protein analysis
      with support for data warehousing and data mining. In this article, we highlight
      the main features of Sting_RDB and show how a user can explore it for efficient
      and biologically relevant queries. Considering its importance for molecular
      biologists, effort has been made to advance Sting_RDB toward data quality
      assessment. To the best of our knowledge, Sting_RDB is one of the most
      comprehensive data repositories for protein analysis, now also capable of
      providing its users with a data quality indicator. This paper differs from our
      previous study in many aspects. First, we introduce Sting_RDB, a relational
      database with mechanisms for efficient and relevant queries using SQL. Sting_rdb
      evolved from the earlier, text (flat file)-based database, in which data
      consistency and integrity was not guaranteed. Second, we provide support for data
      warehousing and mining. Third, the data quality indicator was introduced. Finally
      and probably most importantly, complex queries that could not be posed on a text
      based database, are now easily implemented. Further details are accessible at the
      Sting_RDB demo web page: http://www.cbi.cnptia.embrapa.br/StingRDB.

PMID- 18058713
TI  - Electrostatic potential calculation for biomolecules--creating a database of pre
      calculated values reported on a per residue basis for all PDB protein structures.
AB  - STING and Java Protein Dossier provide a collection of physical-chemical
      parameters, describing protein structure, stability, function, and interaction,
      considered one of the most comprehensive among the available protein databases of
      similar type. Particular attention in STING is paid to the electrostatic
      potential. It makes use of DelPhi, a well-known tool that calculates this
      physical-chemical quantity for biomolecules by solving the Poisson Boltzmann
      equation. In this paper, we describe a modification to the DelPhi program aimed
      at integrating it within the STING environment. We also outline how the "amino
      acid electrostatic potential" and the "surface amino acid electrostatic
      potential" are calculated (over all Protein Data Bank (PDB) content) and how the
      corresponding values are made searchable in STING_DB. In addition, we show that
      the STING and Java Protein Dossier are also capable of providing these particular
      parameter values for the analysis of protein structures modeled in computers or
      being experimentally solved, but not yet deposited in the PDB. Furthermore, we
      compare the calculated electrostatic potential values obtained by using the
      earlier version of DelPhi and those by STING, for the biologically relevant case
      of lysozyme-antibody interaction. Finally, we describe the STING capacity to make
      queries (at both residue and atomic levels) across the whole PDB, by looking at a
      specific case where the electrostatic potential parameter plays a crucial role in
      terms of a particular protein function, such as ligand binding. BlueStar STING is
      available at http://www.cbi.cnptia.embrapa.br.

PMID- 18058714
TI  - BNDb--Biomolecules Nucleus Database: an integrated proteomics and transcriptomics
      database.
AB  - Proteomics correspond to the identification and quantitative analysis of proteins
      expressed in different conditions or life stages of a cell or organism. Methods
      used in proteomics analysis include mainly chromatography, two-dimensional
      electrophoresis and mass spectrometry. Data generated in proteomics analysis vary
      significantly, and to identify a protein it is often necessary to perform a
      series of experiments, comparing its results to those found in proteomics
      databases. Existing proteomics databases are usually related to only one type of
      experiment or represent processed results, not raw data. Therefore, proteomics
      researchers frequently have to resort to several data repositories in order to be
      able to perform the identification. In this paper, we propose an integrated
      proteomics and transcriptomics database that stores raw and processed data, which
      are indexed allowing them to be retrieved together or individually. The proposed
      database, dubbed BNDb for Biomolecules Nucleus Database, is implemented using an
      MySQL server and is being used to store data from the parasite Schistosoma
      mansoni, the scorpion Tittyus serrulatus and the spider Phoneutria nigriventer.
      The database construction uses a relational approach and data indexes. The data
      model proposed uses groups of tables for each data subtype, which store details
      regarding the experimental procedure as well as raw data, analysis results and
      associated publications. BNDb also stores transcriptomics data publicly available
      which are associated with identifications performed on new samples. By using
      BNDb, we expect not only to contribute to proteomics research but also to provide
      a useful service for the scientific community.

PMID- 18058716
TI  - A simple genetic algorithm for multiple sequence alignment.
AB  - Multiple sequence alignment plays an important role in molecular sequence
      analysis. An alignment is the arrangement of two (pairwise alignment) or more
      (multiple alignment) sequences of 'residues' (nucleotides or amino acids) that
      maximizes the similarities between them. Algorithmically, the problem consists of
      opening and extending gaps in the sequences to maximize an objective function
      (measurement of similarity). A simple genetic algorithm was developed and
      implemented in the software MSA-GA. Genetic algorithms, a class of evolutionary
      algorithms, are well suited for problems of this nature since residues and gaps
      are discrete units. An evolutionary algorithm cannot compete in terms of speed
      with progressive alignment methods but it has the advantage of being able to
      correct for initially misaligned sequences; which is not possible with the
      progressive method. This was shown using the BaliBase benchmark, where Clustal-W
      alignments were used to seed the initial population in MSA-GA, improving outcome.
      Alignment scoring functions still constitute an open field of research, and it is
      important to develop methods that simplify the testing of new functions. A
      general evolutionary framework for testing and implementing different scoring
      functions was developed. The results show that a simple genetic algorithm is
      capable of optimizing an alignment without the need of the excessively complex
      operators used in prior study. The clear distinction between objective function
      and genetic algorithms used in MSA-GA makes extending and/or replacing objective
      functions a trivial task.

PMID- 18058715
TI  - Finding protein-protein interaction patterns by contact map matching.
AB  - We propose a novel method for defining patterns of contacts present in protein
      protein complexes. A new use of the traditional contact maps (more frequently
      used for representation of the intra-chain contacts) is presented for analysis of
      inter-chain contacts. Using an algorithm based on image processing techniques, we
      can compare protein-protein interaction maps and also obtain a dissimilarity
      score between them. The same algorithm used to compare the maps can align the
      contacts of all the complexes and be helpful in the determination of a pattern of
      conserved interactions at the interfaces. We present an example for the
      application of this method by analyzing the pattern of interaction of bovine
      pancreatic trypsin inhibitors and trypsins, chymotrypsins, a thrombin, a
      matriptase, and a kallikrein - all classified as serine proteases. We found 20
      contacts conserved in trypsins and chymotrypsins and 3 specific ones are present
      in all the serine protease complexes studied. The method was able to identify
      important contacts for the protein family studied and the results are in
      agreement with the literature.

PMID- 18058717
TI  - Application of latent semantic indexing to evaluate the similarity of sets of
      sequences without multiple alignments character-by-character.
AB  - Most molecular analyses, including phylogenetic inference, are based on sequence
      alignments. We present an algorithm that estimates relatedness between
      biomolecules without the requirement of sequence alignment by using a protein
      frequency matrix that is reduced by singular value decomposition (SVD), in a
      latent semantic index information retrieval system. Two databases were used: one
      with 832 proteins from 13 mitochondrial gene families and another composed of
      1000 sequences from nine types of proteins retrieved from GenBank. Firstly, 208
      sequences from the first database and 200 from the second were randomly selected
      and compared using edit distance between each pair of sequences and respective
      cosines and Euclidean distances from SVD. Correlation between cosine and edit
      distance was -0.32 (P < 0.01) and between Euclidean distance and edit distance
      was +0.70 (P < 0.01). In order to check the ability of SVD in classifying
      sequences according to their categories, we used a sample of 202 sequences from
      the 13 gene families as queries (test set), and the other proteins (630) were
      used to generate the frequency matrix (training set). The classification
      algorithm applies a voting scheme based on the five most similar sequences with
      each query. With a 3-peptide frequency matrix, all 202 queries were correctly
      classified (accuracy = 100%). This algorithm is very attractive, because sequence
      alignments are neither generated nor required. In order to achieve results
      similar to those obtained with edit distance analysis, we recommend that
      Euclidean distance be used as a similarity measure for protein sequences in
      latent semantic indexing methods.

PMID- 18058718
TI  - Prediction and biochemical characterization of intrinsic disorder in the
      structure of proteolysis-inducing factor/dermcidin.
AB  - Proteolysis-inducing factor/dermcidin (PIF/DCD) is a novel human gene, located on
      chromosome 12, locus 12q13.1, that encodes a secreted 110-amino acid protein. Two
      transcripts for the protein have been identified in normal skin, breast, placenta
      and brain, and in various primary and metastatic tumor cells. The putative native
      state structure of PIF/DCD has not been resolved. Here, we describe some
      biochemical features of the soluble recombinant 11-kDa protein produced in
      Escherichia coli. The native 11-kDa polypeptide displayed an anomalous mobility
      on 1% SDS-PAGE under reduced conditions and appeared as a single approximately 16
      kDa band. Under nonreduced conditions, we detected by mass spectrometry, the
      presence of multiple peaks corresponding to m/z values of 21 kDa, which we
      confirmed as a dimeric form with a disulfide bridge between cysteine 34 of each
      11-kDa monomer. The native protein exhibited an unusually high susceptibility to
      proteolytic attack by trypsin, and up to 13 peptides derived from its C-terminus
      were produced after 5 min of incubation. The secondary structure analysis of
      PIF/DCD native protein in aqueous solution, by circular dichroism spectroscopy,
      revealed regions with non-well-defined secondary structure but that acquired
      alpha-helix and beta-sheet secondary structures in the presence of TFE/water
      mixtures and micellar and non-micellar SDS molecules. By using PONDR, DisEMBL,
      DisProt, and GlobPlot computational predictors, we identified a long disorder
      region at the N-terminus of PIF/DCD amino acid sequence. This segment (from 19-50
      residues) is critical for some of its biological activities, including neuron
      survival. This result is coherent with successive failure of crystallization of
      the protein. Taken together, these data suggest that the disorder and order
      transition may be relevant for some biological functions of PIF/DCD.

PMID- 18058719
TI  - Assessment of prolactin secretion in children: a profile of circadian prolactin
      secretion and the principles for interpreting it.
AB  - INTRODUCTION: Prolactin (Prl) is secreted in a circadian pattern, although no
      method of interpreting it has yet been established. The aim of the study was to
      assess Prl secretion in children on the basis of the Prl circadian profile and to
      establish principles for the interpretation of the results obtained by this
      method. MATERIAL AND METHODS: The analysis comprised 41 healthy short children
      (25 boys); aged 5.2-16.3 years, in whom hormonal disorders and chronic diseases
      had been excluded. The children were divided into prepubertal or pubertal
      subgroups. Serum Prl concentrations were measured every 3 hours for 24 hours. To
      assess the rhythm the parameters of macroscopic analysis were calculated and
      receiver operating characteristic (ROC) analysis was performed. The group for
      comparison consisted of 30 children aged 8.9-17.2 years with hyperprolactinaemia.
      RESULTS: In each subgroup significantly higher Prl concentrations were observed
      at night than by day. No statistical differences were noticed between the groups
      regarding Prl concentrations at particular time points or parameter values during
      circadian Prl rhythm evaluation. In the group analysed weak correlations were
      found between age and Prl peak and trough levels. On the basis of ROC analysis
      criteria for the existence of normal circadian Prl rhythm in children were
      established. CONCLUSIONS: 1. The presence of normal circadian Prl rhythm is
      observed if at least one of the following three criteria is fulfilled: amplitude
      >1.8779; X(n)/X(d) ratio >1.685; regression index <-0.4107. 2. No interpretation
      in relation to sex, age and stage of puberty is necessary for the circadian
      prolactin secretion rhythm in children.

PMID- 18058720
TI  - [Causes of precocious puberty in children referred for evaluation in hospital
      conditions].
AB  - INTRODUCTION: Symptoms of precocious puberty (PP) in children always arouse
      anxiety in their parents. Many children with PP are being hospitalized for the
      detailed diagnostic work-up. The aim of our study was to analyze the frequency of
      the variants of PP in children referred to our department. MATERIAL:
      Retrospective analysis of 119 children (103 girls and 16 boys) referred for
      hospitalization in the years 2003-2005 due to signs of precocious puberty was
      performed. RESULTS: Premature thelarche, benign variant of puberty, was diagnosed
      in 62 (53%) girls, in the mean age of 3.39 (+/- 2.33) years. Their mean height
      was within 0.7 +/- 1.1 SD. Premature pubarche was diagnosed 30 (25%) children--22
      girls and 8 boys in the mean age was 7.24 (+/- 0.81) years. Their mean height was
      1.3 +/- 1.0 SD and was significantly higher than normal (p < 0.0001). Premature
      menarche was diagnosed in 8 (7%) girls in the mean age 4.81 +/-2.26 years. Mean
      height in this group was normal for age (0.9+/-0.8 SD). PP was diagnosed in 19
      (16%) children (11 girls and 8 boys) in the mean age 5.91 +/- 1.63 years. Mean
      height in this group was 1.6 +/- 0.7 SD, and was significantly higher than the
      mean for age (p<0.0005). GnRH-dependent type was present in 15 children,
      diagnosed as idiopathic in 9 girls and 1 boy. In 5 children (4 boys and 1 girl)
      pathology of central nervous system was found. In 4 children GnRH-independent
      precocious puberty was diagnosed--in 3 caused by congenital adrenal hyperplasia
      and in 1 boy by tumour of testis (leydigioma). CONCLUSIONS: Girls with precocious
      thelarche without growth acceleration present the benign variant of puberty and
      need clinical follow up only. Boys with clinical signs of precocious puberty
      should be carefully evaluated to rule out the organic cause.

PMID- 18058721
TI  - Assessment of intraorbital structure volume using a numerical segmentation image
      technique (NSI): the fatty tissue and the eyeball.
AB  - INTRODUCTION: Measurement of the degree of exophthalmos is one of the main
      methods used in the assessment of pathological processes that occur in the
      orbital space and is widely used. However, this only provides initial information
      about the volume relations between the intraorbital structures. The aims of our
      work were as follows: to draw up a new computer application, namely the numerical
      segmentation image (NSI) technique, for the automatic calculation of the volume
      of the intraorbital structures on the basis of magnetic resonance imaging (MRI)
      images, to determine its usefulness in the segmentation of fatty tissue and the
      eyeball and to estimate their volume in relation to the degree of exophthalmos.
      MATERIAL AND METHODS: A total of 45 patients (90 orbits) were included in the
      study. All the patients underwent MRI examination of the orbits by a 1.5 T
      scanner using a head coil. The degree of exophthalmos was determined clinically
      and radiologically in relation to the interzygomatic line. Quantitative
      assessment of the eyeball and fatty tissue was made using an NSI application.
      RESULTS: The influence of fatty tissue volume on the degree of exophthalmos was
      determined as being statistically significant (r = 0.367, p = 0.000374) but was
      smaller in comparison with the relationship between total eye muscle volume and
      degree of exophthalmos; eyeball volume was found to have the least influence (r =
      0.344, p = 0.000374). Two eyeballs of significantly smaller volume were found in
      the group of 90 orbits analysed. CONCLUSIONS: The NSI technique is a clinically
      useful application, providing objective data calculated individually for each
      orbit. A credible protocol for estimating the degree of exophthalmos on the basis
      of the NSI technique should include the eye muscle volume, fatty tissue volume
      and, in cases where eyeball pathologies coexist, the eyeball volume as well.

PMID- 18058723
TI  - A comparison of the effectiveness, tolerability and safety of high and low
      carbohydrate diets in women with gestational diabetes.
AB  - INTRODUCTION: Nutrition therapy is an integral part of the management of
      gestational diabetes mellitus (GDM). Most women with GDM are treated by
      nutritional management alone. The goal of our study was to compare low and high
      carbohydrate diets in their effectiveness, safety and tolerability in women with
      GDM. MATERIAL AND METHODS: The study group consisted of 30 Caucasian women newly
      diagnosed with GDM, with a mean age of 28.7 +/- 3.7 years and pregnancy duration
      of 29.2 +/- 5.4 weeks. The patients were randomised into two groups: those on a
      low and those on a high carbohydrate diet (45% vs. 65% respectively of energy
      supply coming from carbohydrates). The presence of urine ketones was controlled
      every day. After two weeks daily glucose profiles and compliance with the
      recommended diets were analysed. RESULTS: Glucose concentration before
      implementation of the diet regimen did not differ between groups. No changes in
      fasting blood glucose were noticed in the group that had followed a low
      carbohydrate diet, although a significant decrease in glucose concentration was
      observed after breakfast (102 +/- 16 vs. 94 +/- 11 mg/dl), lunch (105 +/- 12 vs.
      99 +/- 9 mg/dl) and dinner (112 +/- 16 vs. 103 +/- 13 mg/dl) (p < 0.05). In the
      high carbohydrate diet group fasting and after-breakfast glucose concentration
      did not change. A significant decrease in glycaemia was noticed after lunch (106
      +/- 15 vs. 96 +/- 7 mg/dl) and dinner (107 +/- 12 vs. 97 +/- 7 mg/dl) (p < 0.05).
      Ketonuria was not observed in either group. Obstetrical outcomes did not differ
      between groups. CONCLUSIONS: Both high and low carbohydrate diets are effective
      and safe. A diet with carbohydrate limitation should be recommended to women who
      experience the highest glycaemia levels after breakfast.

PMID- 18058722
TI  - [Analysis of Fas, FasL and Caspase-8 expression in thyroid gland in young
      patients with immune and non-immune thyroid diseases].
AB  - INTRODUCTION: Apoptosis, programmed cell death is a regulating mechanism enabling
      the removal of superabundantly produced and unnecessary at the certain moment
      cells. Disturbances of the apoptosis regulation contribute to the pathogenesis of
      many diseases, including autoimmune thyroid disorders. The aim of this study was
      to estimate expression of proapoptotic Fas/FasL and caspase-8 in thyroid tissues
      in patients with Graves' disease (GD), non-toxic nodular goiter (NTNG) and
      Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: Inclusion criteria of Graves'
      patients were: large goiter, ophthalmopathy, TRAb > 5 U/L, positive titre of anti
      TPO and anti-TG antibodies and concentration of TSH < 0.45 microIU/mL for more
      the 2-3 months from an onset of the disease. Isolated thyrocytes were identified
      by indirect method: in the first stage mouse monoclonal antibodies (mAbs) anti
      TPO were bound to rabbit anti-mouse antibodies IgG (Fab')2 labeled FITC. To
      obtained cellular suspension mAbs directed against apoptotic Fas/FasL molecules
      labeled with PE (Phycoerythrin) was added. All investigations were performed on
      Coulter EPICS XL flow cytometer. Detection of apoptotic proteins was confirmed by
      Western Blot and immunohistochemistry methods using mAbs in DAB chromogene
      visuality and marked by Mayer's haematoxylin. Evaluation of caspase-8 expression
      in thyroid follicular cells was performed by Western Blot test. RESULTS: The
      analysis of Fas and FasL expression on surface of thyroid follicular cells was
      higher in patients with Hashimoto's thyroiditis (38%, 26%) in comparison with
      patients with Graves' disease (18%, 14%). In case of patients with Hashimoto's
      thyroiditis significantly lower percentage of thyroid tissue infiltrating immune
      Fas+ (13%) and FasL+ (22%) T cells in comparison with Graves' patients (33%, 43%
      respectively) was observed . Identification of proapoptotic Fas and FasL
      molecules in the thyroid follicular cells revealed higher expression of both
      proteins in patients with GD (++,++) and HT (+++; +++, respectively) in
      comparison with NTNG patients (+/0; +/0). Caspase-8 expression was detected in
      band 55 kDa using Western Blot test in patients with thyroid autoimmune diseases.
      CONCLUSIONS: We conclude that alteration in the expression of proapoptotic
      proteins in thyroid follicular cells may play a role in pathogenesis of thyroid
      autoimmune disorders. In addition, suppression of apoptosis in Graves' disease
      led to increased proliferation of thyroid follicular cells which is responsible
      for goiter formation.

PMID- 18058724
TI  - Discovery and uses of pegvisomant: a growth hormone antagonist.
AB  - Growth hormone (GH) is a well established participant in several complex
      physiological processes including growth, differentiation, and metabolism.
      Recombinant human GH is a drug that has been approved for use for several
      clinical conditions where the action of GH is diminished or completely lacking.
      Thus there is considerable interest in developing novel drugs that modify the
      function of GH. Only in the last several decades have the detailed structural
      features of GH along with its interaction with its receptor been elucidated. In
      this review we summarise the basic structural and functional properties of GH,
      its receptor and their interaction. In addition, we discuss the discovery and
      development of an effective GH receptor antagonist, pegvisomant, and summarise
      potential therapeutic uses of this drug.

PMID- 18058725
TI  - [Adipose tissue. Pathophysiology, distribution, sex differences and the role in
      inflammation and cancerogenesis].
AB  - The role of adipose tissue is energy storage, but there is increasing evidence
      that adipocytes and adipokines are involved in metabolic and inflammatory
      processes. This paper reviews the pathophysiology of different adipose tissue
      depots. Interrelationships between sex hormones, adipose tissue and risk factors
      are also discussed. Present study focuses on the effects of adipokines on immune
      system and on the mechanisms relating adiposity to cancer risk.

PMID- 18058726
TI  - [Atypical clinical presentation of pseudohypoparathyroidism coexisting with
      autoimmune disorders].
AB  - Pseudohypoparathyroidism includes a genotypically diverse group of syndromes that
      resembles primary hypoparathyroidism but is caused by primary resistance to
      parathormone. Several variants of pseudohypoparathyroidism have been identified,
      and pseudohypoparathyroidism type 1a is the best understood form of the disease.
      In many but not all patients, the disease results from heterozygous inactivating
      mutations of Gs a, the alpha-subunit of the heterotrimeric stimulatory G-protein.
      In this article, we describe the case of a 51-year-old male with clinical picture
      of atypical pseudohypoparathyroidism. The coexistence of this disorder with
      chronic thyroiditis and pernicious anemia suggested that autoimmune processes
      were involved in the mechanism of resistance to parathormone in this patient.

PMID- 18058727
TI  - [Consensus of the Polish Society of Endocrinology. Presurgical somatostatin
      analogs therapy in acromegaly].
AB  - Consensus statement of the Polish Society of Endocrinology, regarding presurgical
      somatostatin analogs in acromegaly has been presented. It is suggested to
      administer depot somatostatin analog (Octreotide LAR at the dose 20 mg and then
      30 mg or equivalent doses of Lanreotide Autogel 90/120 mg every 4 weeks) in order
      to normalize or suppress to a maximal extent GH and IGF-1 concentrations. The
      period of therapy in case of microadenoma would be at least 3 months (targets:
      biochemical improvement, reduced risk of disease's complications, perioperative
      risk reduction, inhibition of tumor growth). The period of therapy in case of
      macroadenoma would be at least 6 months, until maximal possible reduction of GH
      and IGF-1 concentrations (targets: tumor shrinkage, biochemical improvement,
      reduced risk of disease's complications, perioperative risk reduction). Using an
      uniform approach in a group, as numerous as possible, of treated patients would
      allow objective evaluation of long-term efficacy of the treatment.

PMID- 18058729
TI  - The importance of presurgical somatostatin analogue therapy in acromegaly.
AB  - Different types of treatment, including surgery, medical therapy and
      radiotherapy, are possible in achieving control of acromegaly. Of the medical
      therapies available, somatostatin analogues are effective in the majority of
      patients and can induce pituitary tumour shrinkage. The rationale and outcome of
      somatostatin analogue treatment before surgery in patients with acromegaly is
      briefly presented. In summary, the benefits of somatostatin analogues given
      preoperatively should be considered carefully as optimisation of cardiovascular,
      respiratory and metabolic functions is clinically relevant for perioperative
      morbidity. Somatostatin analogues also induce significant shrinkage of GH
      secreting pituitary tumours, although this does not seem to be helpful in terms
      of improved surgical outcome.

PMID- 18058730
TI  - The medical treatment of acromegaly.
AB  - Acromegaly can be treated with several medical modalities. The growth hormone
      (GH) receptor antagonist pegvisomant, in particular, is able to reduce serum
      insulin-like growth factor I (IGF-I) concentrations to almost any desired level.
      Along with this important achievement come other practical issues. The most
      important is that IGF-I also has metabolic actions, especially the control of
      serum glucose concentrations. As somatostatin analogues and pegvisomant have
      their own intrinsic differential effects on serum GH levels and actions as well
      as on serum IGF-I levels and actions, it should not automatically be assumed that
      absolute concentrations of these parameters of disease activity reflect the same
      levels of action. In the ideal situation we should be able to develop treatment
      of specific target levels for both GH and IGF-I that might even be patient
      specific as well. To date we have not moved as far as this, but awareness of
      treatment-specific differential effects might help us to understand some of the
      signs and symptoms that we encounter in acromegalic patients.

PMID- 18058731
TI  - [Natriuretic peptides: their role in diagnosis and therapy].
AB  - Cardiac natriuretic peptide hormones, atrial natriuretic peptide (ANP) and B-type
      natriuretic peptide (BNP), are synthesized and secreted by the heart, producing
      several biological effects, such as natriuresis, vasorelaxation and hypotension.
      During the last decade these peptides, especially BNP, have received increasing
      attention as potential markers of cardiovascular disease. Their measurements can
      be used to diagnose heart failure, including diastolic dysfunction, and using
      them has been shown to save money. BNP levels can enable the differentiation
      between dyspnoic patients secondary to ventricular dysfunction and subjects with
      primary respiratory disorders. Moreover, there is good evidence that natriuretic
      peptides may have a diagnostic role in arterial hypertension, acute coronary
      syndromes, pulmonary hypertension, some valvular heart disease and some disorders
      affecting other systems (diabetes or thyroid disorders). In this paper we discuss
      the clinical utility of assessment of natriuretic peptide hormones in the
      diagnosis of various clinical conditions and their use as pharmacological agents.

PMID- 18058733
TI  - [The importance of bisoprolol in prevention of heart left ventricular hypertrophy
      in patients with long term L-thyroxin suppressive therapy, after the operation of
      differentiated thyroid carcinoma].
AB  - INTRODUCTION: Patients with differentiated thyroid carcinoma have to undergo
      radical surgical treatment, which includes total thyreoidectomy, radioiodine
      therapy and a life-time suppressive therapy with L-thyroxine. The aim of this
      study was a prospective evaluation of left ventricular hypertrophy during L
      suppressive-thyroxine treatment in patients treated for differentiated thyroid
      carcinoma. MATERIAL AND METHODS: The examined group comprised 50 patients with
      differentiated thyroid carcinoma, treated by total thyroidectomy and 131I
      therapy. Echocardiographic measurements were needed for estimation of left
      ventricular mass and its index, according to recommendations of American
      Echocardiography Society. RESULTS: During two-years long suppressive therapy we
      observed a significant rise in left ventricular mass. In woman group left
      ventricular mass was increased from 168+/-39 g to 204+/-45 g (p<0.001) and in men
      from 205+/-60 to 320+/-21 g. Likewise, left ventricular mass index was increased
      in women group from 96+/-18 g/m(2) to 116+/-25 g/m(2) (p<0.001) and in men group
      from 107+/-37 g/m(2) to 158+/-28 g/m(2). Simultaneous treatment with bisoprolol
      caused a regression of left myocardial hypertrophy. Already after 6 months of
      simultaneous treatment with L-thyroxin and bisoprolol, for left ventricular mass
      was reduced to normal: in woman 165+/-35 g, and in men to 178+/-38 g. Analogous
      results were obtained left ventricular mass index. After 6 months it was reduced
      to 94+/-12 g/m(2) in woman and in men to 132+/-32 g/m(2). CONCLUSIONS: 1. In
      differentiated thyroid cancer patients, treated postoperatively with L-thyroxine
      suppressive therapy, left ventricular hypertrophy is observed already during the
      first year of suppressive therapy and progresses during the next year of
      treatment. 2 Addition of a beta-adrenergic antagonist to suppressive doses of L
      thyroxine causes a regression of left ventricular hypertrophy, thus, beta
      adrenergic antagonists should be administered in this group of patients.

PMID- 18058734
TI  - [The thyroid gland function assessment in women after mastectomy and chemotherapy
      during breast cancer therapy].
AB  - INTRODUCTION: For many years much attention has been focused on an interaction
      between the breast disease and the thyroid gland function in the literature. In
      those studies the question whether disease changes in the thyroid gland can
      induces the breast disease was addressed. On the other hand there are a few works
      concerning the inverted question whether the breast cancer therapy, in particular
      after mastectomy and chemotherapy, can disturb the thyroid gland function. The
      aim of the study is to investigate the influence of the mastectomy and
      chemotherapy on the thyroid gland function in women after breast cancer therapy.
      MATERIAL AND METHODS: 173 patients aged 30-80 (average 56) were included in this
      study. The studied group comprised 97 women after breast cancer therapy (average
      age 60). The control group consisted of 76 patients (average age 55). 75 patients
      after mastectomy of the studied group were additionally treated with
      chemotherapy, but in 22 women chemotherapy was not applied. The following methods
      were used to carry out the research: the USG method was applied to evaluate
      thyroid morphological condition in women after mastectomy and chemotherapy; the
      color Doppler technique was used for dynamic presentation and fine- needle
      aspiration biopsy: examination of the thyroid functional state by measuring the
      TSH, fT(3), fT(4) hormone concentration and the level of antithyroid antibodies.
      RESULTS: An average concentration of antithyroid antibodies: anti-TPO and anti-Tg
      was found significantly higher in the studied group of women after chemotherapy,
      comparing with the control group. The level of fT(3) hormone concentration was
      comparable in all investigated groups. Nevertheless, the average concentration of
      TSH was found higher in women after mastectomy and chemotherapy and as a
      consequence leading to hypothyroidism. CONCLUSION: Taking into consideration the
      high level of the concentration of antithyroid antibodies: (anti-TPO and anti-
      Tg), which lead to destruction of the thyroid gland tissue, the thyroid gland
      function of the women after mastectomy and chemotherapy should be monitored
      morphologically as well as functionally.

PMID- 18058735
TI  - [The estimation of the goiter by means of ultrasonography and scintigraphy
      (SPECT) with using 131I].
AB  - INTRODUCTION: Ultrasonography (US) and scintigraphy (SPECT) are used to evaluate
      the volume of thyroid glands. An accurate estimation of the thyroid volume, among
      other factors, is necessary to calculate the suitable radioactive iodine dose,
      which determines the success of the therapy. The aim of the study was to estimate
      the volume of the goiter by means of US and (131)I-SPECT. MATERIAL AND METHODS: A
      group of 80 patients with a thyroid disorder in their past medical history was
      examined. Patients were divided into two groups. The group A contained 50
      patients (39 females, 11 males) with a goiter, where the volume of the thyroid
      was evaluated with the use of US and (131)I-SPECT. The group B contained 30
      patients (21 females, 9 males) with a normal volume of the thyroid gland shown by
      US and (131)I-SPECT. US of the thyroid gland was made by means of an ALOKA SSD
      500 device, with the linear head 7.5 MHz frequency. (131)I-SPECT was made by
      means of a one head gammacamera Diacam with a high energy collimator. RESULTS: In
      the group A, the average volume of the goiter was 44.55 ml in US and 49.67 ml in
      SPECT (p<0.001). In control group B the average volumes of the thyroid gland were
      respectively 13.83 ml vs. 16.19 ml (p<0.001). CONCLUSION: The results of the
      thyroid volume measurement was dependent on the method used in both the
      investigated and control groups.

PMID- 18058736
TI  - [Pegvisomant--growth hormone receptor antagonist in the treatment of acromegaly].
AB  - INTRODUCTION: Pegvisomant, growth hormone (GH) antagonist is a new perspective in
      the treatment of acromegaly. Pegvisomant interferes with GH action by competitive
      binding to receptor and blocking signal transduction. We present first
      experiences with treatment acromegaly with pegvisomant in Poland. Aim of the
      study was to assess pegvisomant efficacy in treatment patients with persistent
      acromegaly after transspheno-ideal surgery and unsatisfactory disease control
      with somatostatin analogue octreotide (OCTR). MATERIAL AND METHODS: Material
      consisted of 10 patients (6 M, 4 F) aged 24-48 with active acromegaly, after
      neurosurgery, in which OCTR was ineffective in disease control. Patients with
      glucose metabolism disturbances were assigned to group receiving PEG. Controls
      were matched for age, sex, disease history, GH and IGF-1 levels. Patients
      received pegvisomant throughout 12 weeks, then combined therapy with PEG and OCTR
      LAR was started for 8 weeks and then OCTR-LAR alone was given for next 8 weeks.
      Controls were medicated with OCTR-LAR 30 mg each 4 weeks during study. Clinical
      symptoms and IGF-1 level, fasting glucose and HbA(1c) was measured to assess
      treatment efficacy. RESULTS: Pegvisomant reduced IGF-1 after first week of
      therapy from 1270+/-229 to 759+/-223 (40%, p<0.04). Prolonged therapy led to
      further IGF-1 decrease. After 12 weeks of treatment IGF-1 was significantly lower
      in comparison to initial as well as to controls (604 mg/l vs. 1270 and 1330,
      respectively, p<0.02). Combined therapy with PEG and OCTR-LAR was not superior to
      PEG alone. During treatment with pegvisomant improvement of glucose metabolism
      was seen, as well as decrease in insulin doses required. No adverse events was
      recorded. CONCLUSIONS: Pegvisomant--GH receptor antagonist--effectively lowers
      IGF-1 concentration and improves disease control in patients with acromegaly
      after unsuccessful surgery and with octreotide unresponsiveness. Significantly
      improves glucose metabolism. Pegvisomant is indicated in patients with active
      acromegaly after standard treatment failure, especially in cases of coexistent
      diabetes mellitus.

PMID- 18058737
TI  - [Diagnostic difficulties in adrenal incidentaloma--analysis of 125 cases].
AB  - INTRODUCTION: Therapeutic approach to incidentaloma, in spite of existing
      algorithms, is not always obvious due to diagnostic difficulties. The aim of the
      study was to assess the validity of the initial diagnoses of incidentaloma which
      determined the qualification for the operation. MATERIAL AND METHODS: 125
      patients hospitalised in the Endocrinology Dept. of the Medical University of
      Bialystok in the years 2003-2005 and in the Endocrinology dept. of Voivodeship
      Hospital of Bialystok. The patients were clinically and hormonally examined
      (metanephrines in daily urine collection, daily cortisol rhythm, short
      dexamethasone test, aldosterone, and renin plasma activity, Na, K levels in the
      serum) as well as computer tomography of the adrenal glands were performed.
      RESULTS: 42 patients were qualified for adrenalectomy. Adenoma was confirmed in
      25 patients (in 7 subclinical Cushing syndrome was diagnosed, in 2 Conn disease,
      in 16 inactive changes), phaeochromocytoma in 6 patients, cysts in 3, lipoma in
      2, carcinoma in one, in 4 patients metastases (in 2 of kidney carcinoma, in 1 of
      malignant melanoma and in 1 of planocellular carcinoma) and in one oncocytoma.
      Metanephrines urine measurements showed 33% of false positive results.
      CONCLUSIONS: Qualification for adrenalectomy requires an assessment of tumor's
      enlargement, its tissue density, morphology and growth dynamics. To reduce the
      percentage of false positive results of metanephrine measurement there is to
      eliminate an influence of some drugs, victuals, beverages and nicotine and
      eventually to carry out additional tests. The decision as to proceeding with
      adrenal incidentaloma should be individualized based on clinical symptoms,
      hormonal tests and tumor morphology.

PMID- 18058738
TI  - Plasma orexin and ghrelin response to the oral glucose tolerance test in obese
      women.
AB  - INTRODUCTION: The aim of the present study was to examine the response of plasma
      orexin and ghrelin to the oral glucose tolerance test (OGTT) in obese women
      without additional disease. MATERIAL AND METHODS: The study group comprised 15
      obese women aged 30.4+/-9.7 years of mean BMI 34.7+/-3.8 kg/m(2). The
      measurements were performed after an overnight fast and 30, 60 and 120 minutes
      after the oral administration of 75 grams of glucose. Serum concentrations of
      ghrelin and orexin A were measured by an enzyme-linked immunosorbent assay
      (ELISA) kit. Serum concentrations of insulin were measured by radioimmunoassay
      (RIA). Plasma glucose was determined by an enzymatic procedure. Body composition
      was determined by impedance analysis using Bodystat. RESULTS: We observed no
      significant differences between serum concentrations of ghrelin and orexin during
      OGTT. No correlations were found between serum ghrelin and orexin concentrations
      and serum insulin and glucose concentrations in any of the measurements.
      CONCLUSION: Oral glucose administration did not change serum concentrations of
      ghrelin and orexin A in obese women without additional disease.

PMID- 18058739
TI  - Oestradiol and tamoxifen inhibit murine Colon 38 cancer growth and increase the
      cytotoxic effect of fluorouracil.
AB  - The poor efficacy of reference chemotherapy (fluorouracil -FU) in colon cancer
      has resulted in a constant search for agents which could augment the action of
      FU. Epidemiological data, such as the decreased risk of colorectal cancer among
      menopausal women receiving hormonal replacement therapy, indicate the role of
      oestrogen in the pathogenesis of this disease. The differences between normal and
      neoplastic colon cells in the expression of oestrogen receptor beta (ERbeta)
      could confirm this association. However, the direct influence of oestrogen or
      tamoxifen (SERM, selective oestrogen receptor modulator) on colon cancer growth
      has rarely been studied. The aim of the present study was to examine the direct
      effects of various concentrations of oestradiol and tamoxifen (10(-4) to 10(-12)
      M), applied alone or together with FU, on the growth of murine Colon 38 cancer in
      vitro as assessed by three colorimetric methods: Mosmann's method, incorporation
      of BrdU into cell nuclei and the TUNEL method. At high concentrations oestradiol
      and tamoxifen decreased the cancer growth in a dose- and time-dependent manner
      (the Mosmann and BrdU methods) and at some concentrations augmented the cytotoxic
      action of FU (Mosmann's method). Tamoxifen exerted a very early and potent
      inhibitory effect, inducing even total cancer growth inhibition at the
      concentration of 10(-4) M (the Mosmann and BrdU methods). All the substances
      studied at different concentrations and at different incubation time points
      increased the apoptosis of tumour cells (the TUNEL method). The results indicate
      that oestradiol and tamoxifen inhibit Colon 38 cancer growth and increase the
      cytotoxic effect of FU, which confirms the role of sex steroids in colon
      carcinogenesis and even suggests new therapeutic schemes.

PMID- 18058741
TI  - [Some problems with testosterone determination].
AB  - Testosterone is the main male sex hormone which determination is useful for
      assessment of androgen status. It seems that serum levels of testosterone, when
      assayed by commonly used methods, do not correlate with clinical parameters. One
      of the causes may be that these assays are suitable for determination of total
      testosterone, but not for measurement of biologically active forms of this
      hormone. The aim of this review is to present usefulness of testosterone
      measurement and its bioactive forms determination as well as factors influencing
      on their levels.

PMID- 18058740
TI  - [Corticosteroids effect on angiogenesis in heart muscle].
AB  - The process of angiogenesis in a heart muscle is a way of providing the ischaemic
      myocardium with oxygen and nutritive ingredients. This natural process called
      therapeutic angiogenesis has been tried in the treatment of patients with
      coronary artery disease mainly. It has been seen as a chance of an effective
      beneficial therapy particularly in these patients for whom pharmacological
      treatment is not sufficient and who are disqualified for operative methods such
      as the percutaneous coronary angioplasty, or coronary bypass transplantation. The
      goal of therapeutic angiogenesis is to stimulate the growth of new capillaries in
      a heart and, as a result, to improve the perfusion and function of a heart
      muscle. The positive impact of the angiogenesis in a heart muscle is impeded in
      patients using corticosteroids in treatment for other illnesses. Corticosteroids
      inhibit the angiogenesis process on a cellular and tissue level. They decrease
      gene expression for VEGF, iNOS, inhibit the activity of transcriptive factors for
      AP-1 and NF(k)B. Corticosteroids cause the degradation of a pericellular matrix,
      inhibit the migration of macrophages and inhibit the synthesis of NO and
      interleukin. These activities of corticosteroids decrease the number of new
      vessels in a ischaemic myocardium and, consequently, worsen vascularization and
      progressive hypoxia.

PMID- 18058742
TI  - [A case of hypophyseal and pineal germinoma].
AB  - A case of 19-year-old male with idiopathic diabetes insipidus diagnosed 9 years
      ago. 1.5 years from the onset of the disease vision disturbances, neurologic
      deficiencies and symptoms of hypopituitarism showed up. MRI examination revealed
      an advanced hypophyseal and pineal gland tumor--germinoma. Total regression was
      achieved with radio- and chemotherapy. For 7 years from the end of treatment
      patient has not declared any complains except for vision disturbances and
      hypopituitarism has been substituted successfully. The case puts on the necessity
      of a strict endocrinologic and radiologic follow-up in patients with idiopathic
      diabetes insipidus due to the possibility of existing potentially curable disease
      ie. intracranial tumor.

PMID- 18058743
TI  - [Thyrotropin reference range--should it be changed?].
AB  - Current thyrotropin (TSH) reference range established by sensitive assays is from
      0.2-0.4 mj.m./l to 4.0-4.5 mj.m./l. Serum TSH reference range was performed using
      specimens from healthy volunteers without history of thyroid disease but the
      values distribution is not concordant with Gaussian curve and is skewed toward
      upper values. It is claimed that upper reference limit for TSH should be declined
      because of possible incorporation of individuals with unrecognized chronic
      lymphocytic thyroiditis into initial study. American National Academy of Clinical
      Biochemistry recommends to examine only euthyroid healthy volunteers without
      personal or family history of thyroid dysfunction, visible or palpable goiter,
      with no detectable thyroid antibodies measured by sensitive immunoassays and
      without any medication except estrogen. Many authors observed that even in such
      rigorously selected population the upper limit of TSH does not decrease
      significantly. The other possible factors which may influence TSH values are
      ethnic features, age, iodine intake, time of phlebotomy or assay sensitivity and
      specificity. Furthermore there are no epidemiological data showing adverse
      consequences of serum TSH between 3.0 mj.m./l and 5.0 mj.m./l. And because of it
      current upper limit for TSH should remain unchanged. However one must realize
      that many people with TSH values between 3.0 mj.m./l and 5.0 mj.m./l have
      unrecognized chronic lymphocytic thyroiditis and should be followed because of
      possible future hypothyroidism. The special care is needed for pregnant women or
      those planning to be pregnant.

PMID- 18058746
TI  - Endopiriform nucleus connectivities: the implications for epileptogenesis and
      epilepsy.
AB  - Several anterograde and retrograde tracing studies have provided detailed
      information on the afferent and efferent projections as well as the intrinsic
      connectivities of the endopiriform nucleus (EN). Here, we summarise EN
      connectional data and the principles of their organisation and discuss the role
      they may play in the development and spread of epileptic seizures.

PMID- 18058747
TI  - Popliteal artery aneurysms: a review.
AB  - Popliteal artery aneurysms (PAAs) are the most common form of peripheral arterial
      aneurysms. The popliteal artery is the continuation of the femoral artery and
      represents the major source of blood to the leg. Thrombus formation as a result
      of PAA may reduce blood flow, leading to limb-threatening ischemia and potential
      limb amputation. Popliteal artery aneurysms are predominantly seen in males (95
      99% of cases), presumably owing to their predisposition for arteriosclerosis,
      which is also a major factor for PAA predisposition. Additionally, it is not
      uncommon to see an abdominal aortic aneurysm associated with a PAA (30-50% of
      cases) or bilateral presentation of PAA (approximately 50% of cases). A
      consequence of a PAA and thrombus located in the popliteal fossa is an
      inflammatory reaction, potentially involving adjacent structures in the fossa.
      This may present clinically as pain in the leg and/or edema. Treatment of PAA
      involves either a conservative management protocol or a more aggressive
      intervention such as surgery. Proponents of conservative management will regulate
      the diameter of the aneurysm by ultrasound, while those in favor of surgical
      intervention will repair the aneurysm through a number of open surgical methods
      or by endovascular stent grafting. This review summarizes the historical points
      related to PAA and analyzes the pertinent anatomical implications, clinical
      findings and treatment methods for PAA.

PMID- 18058749
TI  - The initial zones of the atrioventricular node: really neglected anatomical
      features of potential clinical significance?
AB  - The constant evolution of medical knowledge and accompanying development of
      diagnostic and treatment possibilities for arrhythmias and conduction
      disturbances has reawakened interest in the structure and function of the
      conduction system of the human heart, especially in the region of the
      atrioventricular (AV) junction and within the junction itself. Of the large
      number of studies dealing with the AV junction few focus on the initial zones of
      the AV node. These were described for the first time by Tawara in 1906.
      Similarly, Anderson et al. distinguished two origins of the AV node, the left one
      running towards the basis of the mitral valve and the right one leading towards
      the tricuspid valve. The differences in length and scale could be the result of
      the adoption of different reference points. The study was carried out on the
      material of 50 human hearts, of both sexes and ranging in age from 22 to 93,
      which were fixed in 10% formalin and 98% ethanol solution. The tissue obtained
      was fixed in the 10% formalin solution and, after being sunk in the paraffin, was
      cut into layers of about 10 mum thick. According to the age of the hearts, every
      10(th) or 6(th) section was stained by the Masson-Goldner method. The
      preparations were examined under a LEICA 2000 and BIOLAR 2 microscope at
      magnifications of 2x to 400x. Each of the 50 examined hearts contained the
      atrioventricular node and its initial parts. We observed that the initial zone of
      the AV node is created by an assembly of cells typical for a conduction system
      that can create three groups that are initially independent of each other and are
      always arranged around the AV nodal artery. In all the hearts examined we found
      at least two initial parts of the node: the superior and inferior. These two
      groups were present in 45 hearts (90%). In the last 5 cases (10%) there was also
      a middle group. No cases were found either with a single initial group or without
      any initial groups. In the sections examined the superior group appeared to be
      first in 27 hearts (54%), while in 23 cases (46%) the inferior group was first.
      The length of each group was measured from its first appearance to its first
      direct contact with the second part. The length of the superior part varied from
      0.15 to 2.91 mm (mean 0.90 +/- 0.6 mm), the inferior from 0.11 to 2.41 mm (mean
      0.88 +/- 0.6 mm) and the middle from 0.67 to 2.21 mm (mean 1.04 +/- 0.7 mm). As
      mentioned above, in all 50 hearts there was a direct connection between the
      atrial muscle and the upper origin of AV node. Furthermore, in all sections
      (100%) the same part of the interatrial septal muscle was connected to the
      compact part of the node. Additionally, in 3 cases (6%) we were able to observe
      direct connections between the muscle fibres running from the fasciculus limbicus
      inferior to the initial zone of the AV node: in 2 cases (4%) with the superior
      group and in 1 case (2%) with the inferior group. In 8% of the material the
      atrial muscle of the supra-orificial zone made direct contact with the superior
      initial group and the compact zone of the node and in 10% there was contact
      between the suborificial muscle and the inferior group and the compact part of
      the node. This configuration was not observed in relation to the middle and
      inferior groups.

PMID- 18058748
TI  - Intestinal malrotations: a review and report of thirty cases.
AB  - Intestinal malrotation is a developmental anomaly affecting the position and
      peritoneal attachments of the small and large bowels during organogenesis in
      foetal life. It has been defined as absent or incomplete rotation and fixation of
      the embryonic gut around the superior mesenteric artery. In the present paper, we
      review the definition, history, embryology/aetiology, epidemiology, symptoms and
      signs, diagnosis and treatment of intestinal malformations. Moreover, we report
      the records of 30 cases of malrotation admitted to our department over a period
      of five years. The final intraoperative diagnosis of the cases presented was
      53.3% pure malrotation, 33.3% malrotation with mid-gut volvulus, 6.7% malrotation
      with duodenal atresia, 3.3% malrotation with Meckel's diverticulum and duodenal
      atresia, and 3.3% malrotation and biliary atresia. Preoperative imaging studies
      were performed for 27 cases and surgical management was successfully conducted
      without any mortality among the cases studied. This article provides an overview
      of basic and clinical aspects of intestinal malrotation. In addition, the signs
      and symptoms, imaging findings, and final intraoperative diagnoses presented by
      the subjects reported on are of potential use and clinical interest.

PMID- 18058750
TI  - The femoral artery and its branches in the baboon Papio anubis.
AB  - The aim of the research was to examine the anatomy of the arterial system in the
      inguinal region, hip and thigh of Papio anubis. No description of this was found
      in the available scientific literature, although, at the same time, the baboon is
      considered to be a good animal model in biomedical research. Macroscopic
      anatomical research was carried out on 20 hind limbs (10 cadavers: 9 male and 1
      female) of adult Papio anubis and the results were then compared with the anatomy
      of the arterial hind limb systems of other apes as described in the literature.
      The circulatory system of the whole body was filled with coloured latex via the
      common carotid artery and internal jugular vein, and traditional methods were
      then used to prepare the vessels. The arterial system in the hind extremity of
      Papio anubis was recorded. The anatomical names of human arteries were used as
      well as the names of those of apes as applied in the literature. The femoral
      artery was the only artery supplying the hind limb of Papio anubis. It started
      under the inguinal ligament as a continuation of the external iliac artery. It
      went down and divided into the popliteal artery, which coursed in the popliteal
      fossa, and the saphenous artery, which passed on the medial side of the thigh and
      leg. The number of smaller branches and the way in which they issued from the
      larger arteries were documented. The external diameter and length of the hind
      limb arteries were measured. It was observed that the cutaneous branches of the
      femoral artery supplied the inguinal and genital regions and the abdominal wall,
      while the deep artery of the thigh was the main vessel of the hip and thigh.

PMID- 18058751
TI  - Distribution of neuronal nitric oxide synthase (nNOS)-immunoreactive elements in
      the rabbit piriform cortex.
AB  - The piriform cortex (PC), the primary olfactory cortex, is involved in the
      processes of learning and stress response and possibly plays an important role in
      epileptogenic activity. The results of several recent studies suggest that those
      PC neurons that contain neuronal nitric oxide synthase (nNOS) may play a key role
      during spatial learning and in the modulation of initiation, propagation and
      generalisation of seizures in various experimental models and may influence
      neuronal vulnerability after epileptic insults. The aim of this study was to
      characterise the pattern of distribution and morphology of nNOS-immunoreactive
      elements in PC of the adult rabbit. The co-localisation of nNOS and calretinin
      (CR) was also studied. The pattern of nNOS-ir within the rabbit PC is similar to
      that described previously in other mammals. The morphology of nNOS-ir elements,
      namely varicose fibres and Cajal-Retzius cells, suggest that NO has an important
      influence on PC function. Surprisingly, in the rabbit PC nNOS-ir elements show a
      very low level of co-localisation with CR-ir.

PMID- 18058752
TI  - The valve of the superior vena cava--the supernumerary structure of the precaval
      segment of the crista terminalis.
AB  - The primitive right sinuatrial valve persists in humans as the crista terminalis,
      the valve of the inferior vena cava and the valve of the coronary sinus, while
      according to the known data the primitive left sinuatrial valve is supposed to
      have no derivatives. Ten human right atria were opened with intercaval incisions
      and the precaval segment of each crista terminalis was studied macroscopically.
      Three specimens did not present any peculiarities at this level, but the other 7
      had sagittal muscle bundles and supernumerary valves in individual arrangements.
      Supernumerary valves were present in 2 specimens, one complete and the second
      fenestrated; these valves were located immediately below the superior vena cava
      orifice and covered the medial end of the crista terminalis. The supernumerary
      valves at the superior vena cava orifice may be termed, mirroring that of the
      inferior vena cava, "valves of the superior vena cava". Their exact frequency of
      occurrence and their embryonic precursors must be further established. The
      presence of such valves in the right atrium may interfere with the flow to the
      right side of the heart, may represent conditions for thrombotic changes and may
      disturb a central venous catheter placement. If present, the valve of the
      superior vena cava will also interfere with the catheter ablation procedures used
      for supraventricular tachycardia.

PMID- 18058753
TI  - Anatomical localisation of the marginal mandibular branch of the facial nerve.
AB  - The marginal mandibular nerve was studied post mortem in 50 human subjects. The
      nerve was found to be presented by one branch (32%), two branches (40%) and three
      branches (28%). The relationship of the nerve to the lower border of the mandible
      was variable: it was either totally above the lower border of the mandible (28%),
      below the mandible (44%) or in 28% of cases lying above and below it. The branch
      which lay below the lower border of the mandible crossed it opposite the masseter
      muscle or opposite the facial artery or else anterior to the facial artery. The
      branches which lay above the lower border of the mandible were always deep into
      the superficial layer of the parotid fascia, while below the mandible all the
      branches ran intrafascially. The termination of the nerve was always deep to the
      muscles of the lower lip. The results of the present study were discussed and
      correlated with the results of other authors from the anatomical and surgical
      points of view. It is concluded that the lower border of the mandible can serve
      as an important landmark to help avoid injury to the nerve; above it a
      subplatysmal flap is satisfactory but below it a subfascial flap is much safer.

PMID- 18058754
TI  - The morphology and distribution of the tendinous chords and their relation to the
      papillary muscles in the tricuspid valve of the human heart.
AB  - The tendinous chords of the tricuspid valve are the predominant type of
      connection between the papillary muscles and the tricuspid valve. Studies
      describing the evolutionary line of these connections are well known. The
      flexibility of particular leaflets of the tricuspid valve varies, as does the
      tension of the blood stream in particular cusps. The present study was performed
      on a group of 96 formalin-fixed adult human hearts, which ranged in age from 18
      to 90 years and gave no evidence of congenital malformations or pathological
      changes. The valves were divided into five types according to earlier studies and
      analysis was made in terms of these types. The tendinous chords and their
      ramifications were counted. The surfaces of particular leaflets were measured.
      The ratio of marginal to ventricular leaflets was counted for each type of
      leaflet in particular types of valves. The parts of the main leaflets supported
      by specific papillary muscles were counted for types 1, 2 and 3. The number of
      tendinous chords decreased in leaflets in particular types of tricuspid valve,
      but the ratio of chords attached to the margins and ventricular surfaces was
      similar. The number of chords for the surface of leaflets (measured in mm2) was
      similar in particular types of valve for all cusps. The most differentiated were
      commissural chords in all types of valve. The ratio of chords attached to the
      margins and ventricular surfaces does not depend on the surface area of the
      leaflets.

PMID- 18058755
TI  - The morphometry of the accessory leaflets of the tricuspid valve in a four
      cuspidal model.
AB  - The tricuspid valve is of great importance because of the progress made in
      operative techniques and invasive cardiology accidents. This structure is more
      differentiated during evolution than the mitral valve. Accessory leaflets, their
      frequency and role are still controversial, despite the fact that they have been
      known from the beginning of the 20th century. The number of leaflets in the
      tricuspid valve grows in an evolutionary line, but the rules governing their
      appearance are still not known. The samples were taken from a group of 107 human
      adult hearts. The four-cuspidal form of the tricuspid valve was used as the
      simplest model to show the appearance of accessory leaflets for anatomical and
      statistical examination. On the basis of the results of this study we conclude
      that the separation of accessory leaflets is a complex process.

PMID- 18058756
TI  - Skeletal units of the human embryonic mandible.
AB  - The development of the mandible was traced on serial sections of 20 human embryos
      aged 5-8 weeks (developmental stages 13-23). Special consideration was given to
      the differentiation of skeletal units proposed by Sperber. The first skeletal
      units, namely the mandibular body, the alveolar unit and the condylar unit, may
      be distinguished in the 7(th) week. The primordia of all units are identified by
      the end of the embryonic period (8 weeks).

PMID- 18058757
TI  - Morphological apsects of the coronary artery in the neonates.
AB  - Knowledge of the morphometric quantities of the coronary arteries in neonates is
      an increasingly vital component in the management of congenital and acquired
      heart disease. Because of the considerable heterogeneity of coronary vasculature,
      what is considered atypical and aberrant or insignificant anatomy is often
      unclear. The purpose of our present study is to define the normal anatomy of
      neonates. This was done by focusing on segment analysis of the coronary arteries,
      which was used to obtain accurate definitions of the length and diameter of the
      coronary network. The lengths, widths and numbers of collateral branches of the
      coronary arteries of neonates were measured. The coronary vessels of 50 neonate
      hearts were visualised post mortem by injection of the coronary arteries with
      opaque X-ray dye for the imaging study. Black ink cast and silver impregnation
      specimens were also studied. The longest segment of the circumflex branches of
      the left coronary arteries was the first, the lengths measuring 7188.5 +/- 839.6
      microm and the diameters 850 +/- 90.8 mum. The lengths of segments II, III and IV
      were 5780 +/- 1182.7 microm, 5397.5 +/- 2070.2 microm and 6932.8 +/- 2236.5
      microm and the diameters were 680 +/- 90.8 microm, 510 +/- 90.8 microm and 408 +/
      77.58 microm respectively. The longest segment of the anterior interventricular
      branches of the left coronary arteries was the first, with lengths of 10151.4 +/-
      1298.6 microm and diameters of 1141.9 +/- 82.1 microm. The lengths of segments
      II, III and IV were 8208.5 +/- 1222.3 microm, 3278.5 +/- 602.4 microm and 5370 +/
      1657.6 mum and the diameters were 971 +/- 82.1 microm, 801.42 +/- 82.1 microm
      and 631.4 +/- 82.1 microm respectively. The lateral branches were increased in
      number in the fourth segment. Its diameters ranged from 157.8 +/- 31.7 microm to
      655.7 +/- 99.7 microm. The main branch of the right coronary artery was short at
      the base of the heart. In the newborn the lateral branches of the right coronary
      artery were short, scattered and curved. Analysis of the data suggests a new
      anatomical system for classifying the vasculature of the coronary arteries in
      neonates.

PMID- 18058758
TI  - A novel formula for the classification of blood vessels according to symmetry,
      asymmetry and hypoplasia.
AB  - A new mathematical formula for calculating the symmetry, asymmetry and hypoplasia
      of blood vessel segments is presented for discussion. The study was conducted
      using the computed tomography (CT) files from 80 patients (34 men and 46 women)
      from the Silesian University Hospital, Silesia, Poland, who were between the ages
      of 12 to 76 and had undergone CT angiography of the circle of Willis. With the
      use of Gradual Angiographic Image Data Analyser software and double shuttled
      glasses, CT files were reconstructed. In addition, 80 renal arteries (RAs) from
      spontaneously aborted foetuses ranging in age from 14 to 30 weeks (24 male and 16
      female) were injected with latex and also included in the study. Digital images
      of the RAs were taken using a Camedia 4040 camera and analysed using original
      analysis software. A novel formula entitled the Vascular Asymmetry Coefficient
      (VAC) was derived for this purpose and displays the differences between the mean
      diameters of blood vessel segments expressed as a percentage of the wider vessel
      with respect to the major diameter. The asymmetrical classification for a
      vascular segment of a vessel is given when the difference between the mean
      diameters of the vascular segment, as represented by the wider vessel, is greater
      than VAC > 10%. The hypoplastic classification is reserved for blood vessels
      where the difference between the diameter of the two segments is expressed as a
      percentage of the wider vessels and is greater than VAC > 40%. While there have
      been inconsistent and arbitrary classifications for the qualitative criteria of
      blood vessels, this newly presented algorithm can be used as a standardised tool
      and has a considerable range of uses, particularly when comparing blood vessel
      symmetry, asymmetry and hypoplasia prior to bifurcation, and unification.

PMID- 18058759
TI  - Factors affecting mandibular residual ridge resorption in edentulous patients: a
      preliminary report.
AB  - The aim of the study was to assess the rate of mandibular residual ridge
      resorption in edentulous patients and to analyse the factors which determine this
      process. A group of 35 edentulous patients aged between 51 and 89 years, with a
      mean age of 74 (65-78) years, were included in the study. Individual factors
      (age, gender and duration of edentulousness), local biochemical parameters (oral
      hygiene and history of periodontal diseases) and systemic biochemical parameters
      (calcium and phosphate metabolism, diet, smoking, alcohol intake and systemic
      diseases), as well as physical factors involved in the process (the use of
      prosthetic dentures), were analysed. The study was performed on the basis of the
      results of dental examinations, assessment of panoramic radiograms, research
      surveys and total calcium and phosphate serum levels, which were determined using
      a calorimetric method. Bone resorption in the mandible affected all the study
      patients to varying extents. More than half the edentulous patients showed a high
      degree of mandibular residual ridge resorption. The duration of mandibular
      edentulism was found to be closely associated with values of the radiological
      IC/IM index, which is generally considered to reflect the degree of mandibular
      resorption. Total calcium serum levels were shown to correlate positively with
      the value of IC/IM index in these patients.

PMID- 18058760
TI  - A case of multiple abnormalities of the azygos venous system: a praeaortic
      interazygos vein.
AB  - The posterior thoracic wall, an area drained by the azygos venous system, is a
      common site for surgical intervention. Since the venous part of the
      cardiovascular system is subject to most common variation, abnormalities in the
      azygos venous system are often reported. Some of the anatomical variants have
      significant clinical implications for computed tomography image assessment and
      mediastinal surgery. During dissection of the posterior mediastinum in a 76 year
      old Caucasian male cadaver we found a rare variation in the azygos venous system.
      The hemiazygos vein drained the left 9th to 11th left posterior intercostal
      veins. While passing ventrally to the aorta at the level of the body of the
      eighth thoracic vertebra it was joined by two separate vessels found to be the
      continuations of the 7th and 8th left posterior intercostal veins. The resultant
      dilated vessel, termed the "interazygos vein", then opened into the azygos vein
      on the right side of the vertebral column. Variation in the azygos venous system
      has often been reported, but the abnormality observed by us appears to be
      extremely rare. The interazygos vein passing ventrally to the aorta may mimic
      enlarged lymph nodes and cause misinterpretation of a computed tomography image
      or, if accidentally damaged during mediastinal surgery, may lead to
      intraoperative haemorrhage. To the best of our knowledge this report provides new
      data of potential clinical significance.

PMID- 18058761
TI  - An unusual union of the intercostobrachial nerve and the medial pectoral nerve.
AB  - Variations in the branching pattern of the intercostobrachial nerve have been
      known to complicate dissection during mastectomy and other procedures involving
      the axilla. We present the case of an 87-year-old Caucasian female, in whom the
      intercostobrachial nerve joined with a separate branch from the medial pectoral
      nerve. The clinical consequences of such a variation may include pectoral muscle
      motor loss, in addition to the commonly reported sensory loss resulting from the
      accidental injury or intentional sacrifice of the intercostobrachial nerve during
      axillary dissection.

PMID- 18058762
TI  - In memory of Professor Jozef Markowski, an anatomist from Lvov.

PMID- 18058763
TI  - Recent advances in CE and CEC of pollutants.
AB  - Recent advances in CE and CEC separation, detection and sample
      preparation/preconcentration methodologies, for the determination of a variety of
      compounds having current or potential environmental relevance, have been
      overviewed. The reviewed literature has illustrated the wide range of CE
      applications available, indicating a continuing interest in CE and CEC in the
      environmental field. New developments in chip-based CE systems are also
      discussed.

PMID- 18058764
TI  - Capillary electrophoresis of proteins 2005-2007.
AB  - This review article with 239 references describes recent developments in
      capillary electrophoresis of proteins, and covers the two years since the
      previous review (V. Dolnik, Electrophoresis 2006, 27, 126-141) through spring
      2007. It includes topics related to CE of proteins, such as sample pretreatment,
      wall coatings, improving separation, various forms of detection, and special
      electrophoretic techniques including ACE, CIEF, capillary ITP, and CEC. The paper
      describes applications of CE to analysis of proteins in real-world samples
      including human body fluids, food and agricultural samples, protein
      pharmaceuticals and recombinant protein preparations.

PMID- 18058765
TI  - Recent advances in the applications of CE to forensic sciences (2005-2007).
AB  - The present article reviews the applications of CE in forensic science covering
      the period from 2005 until the first part of 2007. The overview includes the most
      relevant examples of analytical applications of capillary electrophoretic and
      electrokinetic techniques in the following fields: (i) forensic drugs, toxicants
      and dyes, (ii) small ions of forensic interest (iii) explosives, (iv) forensic
      DNA, and (v) other biopolymers of forensic interest.

PMID- 18058766
TI  - Advances in CE for kinetic studies.
AB  - CE is a promising technique for the investigation of molecular interactions
      because it affords evaluation of multiple interaction modes, does not require
      immobilization of molecules, and has no dead time. In order to perform these
      investigations, numerous methods have been developed for determining binding
      constants and other thermodynamic parameters. These methods have been reviewed
      extensively in recent years. However, methods for determining the rates of
      reaction are less prolific. Nonetheless, numerous theoretical and experimental
      advances have been made in recent years to address this discrepancy. Some of
      these methods employ computer simulations to determine first-order or second
      order rate constants numerically, whereas other methods calculate rate constants
      directly as solutions to analytical equations. It is the object of this review to
      provide descriptions of these methods in terms of their underlying assumptions,
      experimental methodology, calculation of rate constants, and inherent
      limitations.

PMID- 18058767
TI  - Design and applications of coupled SPE-CE.
AB  - CE suffers from an inherent low concentration sensitivity. Analyte detection
      limits can be improved by combining CE with SPE. This paper presents an overview
      of coupled SPE-CE systems that have been reported in literature. Attention is
      paid to fundamental aspects of coupling SPE and CE, as well as to important SPE
      requirements. Interfaces for inline and online coupling with CE are critically
      discussed, and their mode of operation is outlined. Advantages and limitations of
      the interfaces are discussed and typical examples are selected. Finally, some
      future developments are discussed.

PMID- 18058768
TI  - Joule heating in electrokinetic flow.
AB  - Electrokinetic flow is an efficient means to manipulate liquids and samples in
      lab-on-a-chip devices. It has a number of significant advantages over
      conventional pressure-driven flow. However, there exists inevitable Joule heating
      in electrokinetic flow, which is known to cause temperature variations in liquids
      and draw disturbances to electric, flow and concentration fields via temperature
      dependent material properties. Therefore, both the throughput and the resolution
      of analytic studies performed in microfluidic devices are affected. This article
      reviews the recent progress on the topic of Joule heating and its effect in
      electrokinetic flow, particularly the theoretical and experimental
      accomplishments from the aspects of fluid mechanics and heat/mass transfer. The
      primary focus is placed on the temperature-induced flow variations and the
      accompanying phenomena at the whole channel or chip level.

PMID- 18058769
TI  - Recent innovations in protein separation on microchips by electrophoretic
      methods.
AB  - Microchips for analytical purposes have attracted great attention over the last
      20 years. In the present review, we focus on the most recent development of
      microchips for electrophoretic separation of proteins. This review starts with a
      short recalling about the microchips covering the basic microchip layout for CE
      and the commercial chips and microchip platforms. A short paragraph is dedicated
      to the surface treatment of microchips, which is of paramount importance in
      protein analysis. One section is dedicated to on-line sample pretreatment in
      microchips and summarizes different strategies to pre-concentrate or to purify
      proteins from complex matrixes. Most of the common modes used for CE of proteins
      have already been adapted to the chip format, while multidimensional approaches
      are still in progress. The different routes to achieve detection in microchip are
      also presented with a special attention to derivatization or labeling of
      proteins. Finally, several recent applications are mentioned. They highlight the
      great potential of electrophoretic separations of proteins in numerous fields
      such as biological, pharmaceutical or agricultural and food analysis. A
      bibliography with 151 references is provided covering papers published from 2000
      to the early 2007.

PMID- 18058770
TI  - Electrokinetic-based injection modes for separative microsystems.
AB  - Miniaturization of analytical instruments has attracted a wide interest in
      Analytical Chemistry over the past decade because of the advantages such as
      reduced reagent consumption and shorter analysis time. For chips involving
      separation, injection is a key step to achieve efficient and sensitive analysis.
      Electrokinetic injection mode is mostly used in chips because it is easier to
      generate flow motion in microsystems via electric potential control at channel
      extremities than pressure-driven flow. The injection step usually involves
      several intersecting channels. For each injection design, different injection
      modes can be done, depending on electric field sequences and distributions. This
      paper is an up-to-date review of these different modes on a chip.

PMID- 18058771
TI  - Trends in analysis of explosives by microchip electrophoresis and conventional
      CE.
AB  - The continuous upsurge in terrorist activity has generated tremendous demand for
      innovative tools capable of detecting nitrated organic, inorganic, and peroxide
      based explosives. This article directly extends the previous exhaustive review
      (Electrophoresis 2006, 27, 244-256) and overviews the research activity in the
      field of microchip and conventional capillary electrophoresis for analysis of a
      variety of explosive compounds and mixtures in the past two years (middle 2005
      middle 2007), with the focus on world-to-chip interfaces and detection
      techniques.

PMID- 18058772
TI  - Recent advances in amino acid analysis by CE.
AB  - This paper describes a number of articles that have been published on amino acid
      (AA) analysis using CE during the period from June 2005 to May 2007. This review
      article follows the format of the previous articles of Smith (Electrophoresis
      1999, 20, 3078-3083), Prata et al.. (Electrophoresis 2001, 22, 4129-4138), and
      Poinsot et al.. (Electrophoresis 2003, 24, 4047-4062 and Electrophoresis 2006,
      27, 176-194). Several new developments in AA analysis with CE are reported
      describing the use of laser-emitting diodes for LIF, MS, and chips. In addition,
      we describe articles concerning clinical studies and neuroclinical applications.

PMID- 18058773
TI  - Catalytic promiscuity in the alpha/beta-hydrolase superfamily: hydroxamic acid
      formation, C--C bond formation, ester and thioester hydrolysis in the C--C
      hydrolase family.
AB  - The haloperoxidase family of alpha/beta-hydrolases contains enzymes of several
      different catalytic activities, including esterases, C--C hydrolases and cofactor
      independent haloperoxidases (perhydrolases), but the molecular basis of this
      catalytic promiscuity is not fully understood. The C--C hydrolase enzyme MhpC
      from E. coli is shown to possess esterase and thioesterase activity, and the
      ability to activate hydroxylamine as a nucleophile to form hydroxamic acid
      products. The ratio of these activities was examined for nine site-directed
      mutant enzymes that contained mutations at nonessential residues in the enzyme
      active site. Higher levels of esterase and thioesterase activity were found in
      mutants Phe173Gly and Trp264Gly; this might be due to increased amounts of space
      in the active site. Higher levels of hydroxamic acid formation activity were
      found in mutant Asn109His-a mutation found in many haloperoxidase enzymes. Wild
      type and mutant MhpC enzymes were also capable of C--C bond formation in organic
      solvents, and the highest activity was observed in nonpolar solvents. The results
      provide experimental support for the catalytic promiscuity shown in this family
      of enzymes, and indicate that differences in catalytic function can be introduced
      by point mutations.

PMID- 18058774
TI  - Head-to-tail cyclized cystine-knot peptides by a combined recombinant and
      chemical route of synthesis.

PMID- 18058775
TI  - A very stable cyclic DNA miniduplex with just two base pairs.

PMID- 18058776
TI  - A tunable, chemoselective, and moldable biodegradable polyester for cell
      scaffolds.

PMID- 18058777
TI  - Efficient singlet-state deactivation of cyano-substituted indolines in protic
      solvents via CN--HO hydrogen bonds.
AB  - The photophysical properties of indoline (I) and three of its derivatives,
      namely, N-methylindoline (MI), 5-cyanoindoline (CI), and 5-cyano-N-methylindoline
      (CMI), are studied in H-donating solvents of varying polarity. Based on
      measurements of fluorescence yield and lifetime, and of triplet yield and
      hydrated-electron formation, two distinct mechanisms of solvent-induced
      fluorescence quenching are evidenced. The first mechanism involves the cyano
      substituent and leads to an increase in the rate constant of internal conversion
      of one order of magnitude in ethanolic solution and of more than two orders of
      magnitude in water, as compared to solutions in n-hexane or acetonitrile. A
      similar trend had previously been observed in the case of 4-N,N
      dimethylaminobenzonitrile (DMABN). The second mechanism reduces the fluorescence
      lifetimes of the non-cyanated derivatives in aqueous solution by one order of
      magnitude and is related to the formation of hydrated electrons. Neither of these
      mechanisms is influenced by methylation at the ring nitrogen. Quantum chemical
      calculations are performed on the ground and excited states of the hydrogen
      bonded complexes between protic solvents and MI as well as CMI. Stable hydrogen
      bonded configurations involving the CN substituent and a solvent OH group are
      found; these configurations are stable both in the ground and the first excited
      singlet states, whereas the corresponding complex at the ring amino nitrogen is
      stable in the ground state only. The CN--HO configuration is therefore a prime
      candidate for a mechanistic explanation of the observed quenching by the first
      mechanism. These findings may have useful applications for the design of
      fluorescence probes for water in biological systems.

PMID- 18058778
TI  - Polyoxomolybdate-stabilized Ru(0) nanoparticles deposited on mesoporous silica as
      catalysts for aromatic hydrogenation.
AB  - We use polyoxometalates as precursors for the preparation of heterogeneous
      catalysts. In the starting molecular precursor
      [{Ru(C6Me6)}(2)Mo5O18{Ru(C6Me6)(H2O)}], three ruthenium arene fragments are
      supported on a formally lacunary Lindqvist-type polyoxomolybdate. This species
      was introduced by incipient wetness impregnation into the porosity of a SBA-15
      type mesoporous silica. The evolution of the system under reducing atmosphere is
      followed by several methods, such as temperature-programmed reduction (TPR),
      Raman, and X-ray absorption spectroscopy (XAS). The results indicate that the
      polyoxometalate structure is retained after grafting on silica and allows the
      stabilization of Ru(0) nanoparticles after reduction. The resulting system
      exhibits interesting catalytic activity in benzene hydrogenation.

PMID- 18058779
TI  - Extending the light-harvesting properties of transition-metal dendrimers.
AB  - We report a study of the electronic energy-transfer dynamics within the
      transition-metal polypyridine complex OsRu3pyr6 (Os[(dpp)Ru(bpy{pyrene})2]3(8+),
      where dpp=2,3-bis(2'-pyridyl)pyrazine and bpy=2,2'-bipyridine) after excitation
      with UV light. By using a broadband visible femtosecond probe, we are able to
      simultaneously detect both the energy transfer from the peripheral aromatic
      ligands to the Os center and the sub-picosecond energy transfer from the
      initially excited Ru-bpy ligand-centered state to the Os triplet metal-to-ligand
      charge-transfer (MLCT) state. Pyrene energy transfer occurs from both the
      nonrelaxed and the relaxed S(1) states on timescales of 6 and 45 ps,
      respectively. In both cases, the energy transfer is described by means of Forster
      energy transfer theory. Sub-picosecond energy transfer within the OsRu3 metal
      ligand core most likely includes a direct energy transfer between the higher
      lying ligand-centered states on Ru and Os, in addition to the transfer between
      the MLCT states. The absorption cross-sections in both the UV and the visible
      spectral regions are enhanced by attaching the aromatic pyrene ligands.
      Furthermore, energy transfer is directed only towards the Os core, which
      ultimately leads to an exclusive population of the Os-based triplet MLCT state,
      thus making the OsRu3pyr6 transition metal-polypyridine dendrimer an obvious
      candidate for artificial light-harvesting systems.

PMID- 18058780
TI  - Asymmetric synthesis and receptor pharmacology of the group II mGlu receptor
      ligand (1S,2R,3R,5R,6S)-2-amino-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic
      acid-HYDIA.
AB  - The asymmetric synthesis and receptor pharmacology of (1S,2R,3R,5R,6S)-2-amino-3
      Hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (+)-9 (HYDIA) and a few of its
      O-alkylated derivatives are described. The key step of the synthesis utilizes
      Sharpless' asymmetric dihydroxylation (AD-beta) for the kinetic resolution of a
      bicyclic racemic precursor olefin. In contrast to the bicyclic glutamate analogue
      LY354740, which is a potent and selective agonist for the group II metabotropic
      glutamate receptors (mGluRs), these new conformationally restricted and also
      hydroxylated or alkoxylated glutamate analogues are potent and selective
      antagonists for the group II mGluRs.

PMID- 18058781
TI  - ESI-MS studies on prolyl hydroxylase domain 2 reveal a new metal binding site.

PMID- 18058782
TI  - D-SAP: a new, noncytotoxic, and fully protease resistant cell-penetrating
      peptide.
AB  - Protease resistant cell-penetrating peptides (CPPs) are promising carriers for
      drugs unable to cross the cell membrane. As these CPPs are stable in vivo for
      much longer periods of time compared to other classes of therapeutic peptides,
      noncytotoxicity is a property sine qua non for their pharmacological development.
      Described herein is a fully protease resistant CPP that is noncytotoxic at
      concentrations up to 1 mM. Proteolytic stability was obtained by chiral inversion
      of the residues of a known self-assembling CPP-from all L-amino acids to all D
      amino acids-and then assessed against trypsin and human serum. Circular dichroism
      studies confirmed the enantiomeric structure of the analogue, and transmission
      electron microscopy (TEM) studies indicated that the new inverso analogue retains
      the ability of the original peptide to self-assemble. The results of uptake
      experiments indicate that the protease-stable (that is, D-amino acid) analogue of
      the peptide is internalised by cells to the same extent as the protease
      susceptible (that is, L-amino acid) parent peptide. Also reported herein are the
      results of studies on the cellular internalisation mechanism of the all-D
      analogue, which reveal the steps followed by the peptide upon its entry into the
      cell.

PMID- 18058783
TI  - Thermally responsive supramolecular nanomeshes for on/off switching of the rotary
      motion of F1-ATPase at the single-molecule level.
AB  - The artificial regulation of protein functions is essential for the realization
      of protein-based soft devices, because of their unique functions conducted within
      a nano-sized molecular space. We report that self-assembled nanomeshes comprising
      heat-responsive supramolecular hydrogel fibers can control the rotary motion of
      an enzyme-based biomotor (F(1)-ATPase) in an on/off manner at the single-molecule
      level. Direct observation of the interaction of the supramolecular fibers with a
      microbead unit tethered to the F(1)-ATPase and the clear threshold in the size of
      the bead required to stop ATPase rotation indicates that the bead was physically
      blocked so as to stop the rotary motion of ATPase. The temperature-induced
      formation and collapse of the supramolecular nanomesh can produce or destroy,
      respectively, the physical obstacle for ATPase so as to control the ATPase motion
      in an off/on manner. Furthermore, this switching of the F(1)-ATPase motion could
      be spatially restricted by using a microheating device. The integration of
      biomolecules and hard materials, interfaced with intelligent soft materials such
      as supramolecular hydrogels, is promising for the development of novel semi
      synthetic nano-biodevices.

PMID- 18058784
TI  - Thiourea-enhanced flavin photooxidation of benzyl alcohol.
AB  - Upon irradiation, flavin oxidises 4-methoxybenzyl alcohol to the corresponding
      aldehyde using aerial O(2) as the terminal oxidant. We have observed that this
      reaction is significantly accelerated by the presence of thiourea. A series of
      thiourea-functionalised flavins has been prepared from flavin isothiocyanates and
      their photocatalytic efficiencies have been monitored by NMR. The alcohol
      photooxidation proceeds rapidly and cleanly with high turnover numbers of up to
      580, exceeding previously reported performances. A likely mechanistic rationale
      for the more than 30-fold acceleration of the photo-redox reaction by thiourea
      has been derived from spectroscopic, electrochemical, and kinetic studies. Thus,
      thiourea acts as an electron-transfer mediator for the initial photooxidation of
      4-methoxybenzyl alcohol by the excited flavins. This mechanism has similarities
      to electron-relay mechanisms in flavoenzymes, for which cysteine sulfenic acid
      intermediates are proposed. The observation that thiourea mediates flavin photo
      redox processes is valuable for the design of more sophisticated photocatalysts
      based on Nature's best redox chromophore.

PMID- 18058785
TI  - Simulations of p-tert-butylcalix[4]arene with multiple occupancies of small guest
      molecules.
AB  - Classical molecular dynamics simulations were used to study low-density beta(0)
      phase p-tert-butylcalix[4]arene inclusion compounds with multiple calix
      occupancies of xenon, carbon dioxide, methane, and hydrogen guest molecules with
      guest-host ratios ranging from 1:4 to 4:1. Custom parameterized force fields were
      used for the guests and the AMBER force field for the calixarene units was
      validated in our previous work (Chem. Eur. J. 2006, 12, 5231). The inclusion
      energy and unit cell volume of the calixarene inclusion compound were determined
      for various guest occupancies and for occupancies greater than 1:1, strong guest
      guest interaction effects are observed. The structure and energetics of the 2:1
      CO(2)/beta(0)-phase inclusion compound were compared to those of the low
      temperature 2:1 CO(2)/calixarene in which the guest molecules occupy both cage
      and interstitial sites.

PMID- 18058786
TI  - "Click" dendrimers: synthesis, redox sensing of Pd(OAc)2, and remarkable
      catalytic hydrogenation activity of precise Pd nanoparticles stabilized by 1,2,3
      triazole-containing dendrimers.
AB  - "Click" dendrimers containing 1,2,3-triazolyl ligands that coordinate to
      PdII(OAc)2 have been synthesized in view of catalytic applications. Five of these
      dendrimers contain ferrocenyl termini directly attached to the triazole ligand in
      order to monitor the number of PdII that are introduced into the dendrimers by
      cyclic voltammetry. Reduction of the PdII-triazole dendrimers by using NaBH4 or
      methanol yields Pd nanoparticles (PdNPs) that are stabilized either by several
      dendrimers (G0, DSN) or by encapsulation inside a dendrimer (G1 and G2: DEN), as
      confirmed by TEM. Relative to PAMAM-DENs (PAMAM=poly(amidoamine)), the "click"
      DSNs and DENs show a remarkable efficiency and stability for olefin hydrogenation
      under ambient conditions of various substrates. The influence of the reductant of
      PdII bound to the dendrimers is dramatic, reduction with methanol leading to much
      higher catalytic activity than reduction with NaBH4. The most active NPs are
      shown to be those derived from dendrimer G1, and variation of its termini groups
      (ferrocenyl, alkyl, phenyl) allowed us to clearly delineate, optimize, and
      rationalize the role of the dendrimer frameworks on the catalytic efficiencies.
      Finally, hydrogenation of various substrates catalyzed by these PdNPs shows
      remarkable selectivity features.

PMID- 18058787
TI  - Encapsulation of fullerenes in a helical PMMA cavity leading to a robust
      processable complex with a macromolecular helicity memory.

PMID- 18058788
TI  - Are environmentally coupled enzymatic hydrogen tunneling reactions influenced by
      changes in solution viscosity?

PMID- 18058790
TI  - Effect of Cu(II) on the complex between kanamycin A and the bacterial ribosomal A
      site.
AB  - The solution structure of kanamycin A interacting with a ribosomal A-site
      fragment was solved by transferred-NOE techniques and found to agree with the
      structure of the complex observed in the crystal. Despite the fast exchange
      conditions found for the interaction, the bound form was identified by NOESY
      spectroscopy. At 600 MHz, NOE effects are only observed for the RNA-associated
      antibiotic. Dissociation constants were measured by NMR spectroscopy for two
      sites of interaction (K(d1)=150+/-40 microM; K(d2)=360+/-50 microM). Furthermore,
      the effects of the Cu(II) ion on the antibiotic, on the RNA fragment that mimics
      the bacterial ribosomal A site, and on the complex formed between these two
      entities were analyzed. The study led to the proposal of a model that localizes
      the copper ion within the kanamycin-RNA complex.

PMID- 18058789
TI  - Guanidinoneomycin B recognition of an HIV-1 RNA helix.
AB  - Aminoglycoside antibiotics are small-molecule drugs that bind RNA. The affinity
      and specificity of aminoglycoside binding to RNA can be increased through
      chemical modification, such as guanidinylation. Here, we report the binding of
      guanidinoneomycin B (GNB) to an RNA helix from the HIV-1 frameshift site. The
      binding of GNB increases the melting temperature (T(m)) of the frameshift-site
      RNA by at least 10 degrees C, to a point at which a melting transition is not
      even observed in 2 M urea. A structure of the complex was obtained by using
      multidimensional heteronuclear NMR spectroscopic methods. We also used a novel
      paramagnetic-probe assay to identify the site of GNB binding to the surface of
      the RNA. GNB makes major-groove contacts to two sets of Watson-Crick bases and is
      in van der Waals contact with a highly structured ACAA tetraloop. Rings I and II
      of GNB fit into the major groove and form the binding interface with the RNA,
      whereas rings III and IV are exposed to the solvent and disordered. The binding
      of GNB causes a broadening of the major groove across the binding site.

PMID- 18058791
TI  - Elastic modulus variation in mandibular bone: a microindentation study of Macaca
      fascicularis.
AB  - We characterized the heterogeneous anisotropic elastic properties of mandibular
      bone in an adult female specimen of Macaca fascicularis using the technique of
      microindentation. This approach used an indenter of known mass and geometry to
      sample bone hardness at a spatial resolution in the order of 100 mum. Hardness
      values were converted to elastic modulus using empirically derived regression. We
      determined properties in alveolar, midcorpus, and basal regions of coronal and
      transverse sections taken from multiple locations along the corpus and ramus.
      Within sections, we determined properties from endosteal, midcortical, and
      periosteal regions. We found regional variations in bone structure, including
      bands of orthotropic circumferential lamellar bone at the endosteal and
      periosteal corpus base, angular region, and ramus. Transversely isotropic
      osteonal bone characterizes the midcortices of alveolar and basal regions, with
      many resorption spaces in alveolar regions restricting sampling opportunities.
      Regional variations in elasticity include relatively compliant bone in the
      anterior corpus and ramus. Basal cortical bone is stiffer longitudinally than
      transversely or superoinferiorly, while the evidence for directional dependence
      in alveolar bone is equivocal. Alveolar bone appears to be relatively compliant
      with respect to bone found in midcorpus or basal regions. Considerable variation
      exists in structure and material properties on a highly localized scale, more so
      than is discernible through conventional approaches for determining material
      property variation.

PMID- 18058792
TI  - Pharmacokinetics of selected chiral flavonoids: hesperetin, naringenin and
      eriodictyol in rats and their content in fruit juices.
AB  - The majority of pharmacokinetic studies of individual flavonoids or after
      ingestion of foodstuffs have overlooked the chirality of some of these
      xenobiotics. In order to characterize for the first time the stereoselective
      pharmacokinetics of three flavonoids, hesperetin, naringenin and eriodictyol were
      intravenously administered (20 mg/kg) to male Sprague-Dawley rats, and their
      stereospecific content was assessed in various fruit juices. Concentrations in
      serum, urine and fruit juices were characterized via HPLC and verified by LC/MS.
      Short half-lives (3-7 h) in serum were observed, while a better estimation of
      half-life (12-48 h) and the other pharmacokinetic parameters was observed using
      urinary data. The three flavonoids are predominantly excreted via non-renal
      routes (fe values of 3-7%), and undergo rapid and extensive phase II metabolism.
      The (2S)-epimers of the flavonoid glycosides and the S(-)-enantiomers of the
      aglycones were predominant and in some instances the organic fruit juices had
      higher concentrations than the conventional fruit juices. This study reports for
      the first time the stereospecific pharmacokinetics of three chiral flavonoids and
      their stereospecific content in fruit juices. It also reports for the first time
      the stereospecific pharmacokinetics of flavonoids employing urine as a more
      reliable biological matrix.

PMID- 18058793
TI  - Changes in Crohn's disease phenotype over time in the Chinese population:
      validation of the Montreal classification system.
AB  - BACKGROUND: Phenotypic evolution of Crohn's disease occurs in whites but has
      never been described in other populations. The Montreal classification may
      describe phenotypes more precisely. The aim of this study was to validate the
      Montreal classification through a longitudinal sensitivity analysis in detecting
      phenotypic variation compared to the Vienna classification. METHODS: This was a
      retrospective longitudinal study of consecutive Chinese Crohn's disease patients.
      All cases were classified by the Montreal classification and the Vienna
      classification for behavior and location. The evolution of these characteristics
      and the need for surgery were evaluated. RESULTS: A total of 109 patients were
      recruited (median follow-up: 4 years, range: 6 months-18 years). Crohn's disease
      behavior changed 3 years after diagnosis (P = 0.025), with an increase in
      stricturing and penetrating phenotypes, as determined by the Montreal
      classification, but was only detected by the Vienna classification after 5 years
      (P = 0.015). Disease location remained stable on follow-up in both
      classifications. Thirty-four patients (31%) underwent major surgery during the
      follow-up period with the stricturing [P = 0.002; hazard ratio (HR): 3.3; 95% CI:
      1.5-7.0] and penetrating (P = 0.03; HR: 5.8; 95% CI: 1.2-28.2) phenotypes
      according to the Montreal classification associated with the need for major
      surgery. In contrast, colonic disease was protective against a major operation (P
      = 0.02; HR: 0.3; 95% CI: 0.08-0.8). CONCLUSIONS: This is the first study
      demonstrating phenotypic evolution of Crohn's disease in a nonwhite population.
      The Montreal classification is more sensitive to behavior phenotypic changes than
      is the Vienna classification after excluding perianal disease from the
      penetrating disease category and was useful in predicting course and the need for
      surgery.

PMID- 18058794
TI  - Recent methodology in the phytochemical analysis of ginseng.
AB  - This review summarises the most recent developments in ginseng analysis, in
      particular the novel approaches in sample pre-treatment and the use of high
      performance liquid-chromatography-mass spectrometry. The review also presents
      novel data on analysing ginseng extracts by nuclear magnetic resonance
      spectroscopy and high-resolution mass spectrometry (Fourier transform mass
      spectrometry) in the context of metabolomics.

PMID- 18058795
TI  - A survey of sesamin and composition of tocopherol variability from seeds of
      eleven diverse sesame (Sesamum indicum L.) genotypes using HPLC-PAD-ECD.
AB  - The objective of this study was to determine the composition and content of
      sesamin and desmethyl tocopherols such as alpha-tocopherol (alphaT), delta
      tocopherol (deltaT) and gamma-tocopherol (gammaT) in seeds of sesame (Sesamum
      indicum L.) for 11 genotypes conserved in the United States Department of
      Agriculture (USDA), Agricultural Research Service (ARS) and Plant Genetic
      Resources Conservation Unit (PGRCU) in Griffin, Georgia, USA. Seed accessions
      studied were collections from eight countries worldwide, including one landrace
      from Thailand and two cultivars from Texas, USA. Novel methodologies and
      analytical techniques described herein consisted of reverse-phase high
      performance liquid chromatography (HPLC) connected in series with two detection
      systems specific for each analyte class. Photodiode array detection was employed
      for sesamin analysis and electrochemical array detection was used in the
      determination of tocopherols. A preliminary study was conducted to assess sesamin
      levels in 2003 and tocopherol levels in 2004 from sesame seed samples conserved
      at the USDA, ARS and PGRCU. In 2005, sesame seed samples were grown, harvested
      and evaluated for sesamin as well as tocopherol levels. The overall results (n =
      3) showed that sesamin, alphaT, deltaT and gammaT levels were 0.67-6.35 mg/g,
      0.034-0.175 microg/g, 0.44-3.05 microg/g and 56.9-99.3 microg/g respectively,
      indicating that the sesame seed accessions contained higher levels of sesamin and
      gammaT compared with alphaT and deltaT. Statistical analysis was conducted and
      significant differences were observed among the 11 different sesame genotypes.
      This suggests that genetic, environmental and geographical factors influence
      sesamin and desmethyl tocopherol content.

PMID- 18058796
TI  - Profiling of copy number variations (CNVs) in healthy individuals from three
      ethnic groups using a human genome 32 K BAC-clone-based array.
AB  - To further explore the extent of structural large-scale variation in the human
      genome, we assessed copy number variations (CNVs) in a series of 71 healthy
      subjects from three ethnic groups. CNVs were analyzed using comparative genomic
      hybridization (CGH) to a BAC array covering the human genome, using DNA extracted
      from peripheral blood, thus avoiding any culture-induced rearrangements. By
      applying a newly developed computational algorithm based on Hidden Markov
      modeling, we identified 1,078 autosomal CNVs, including at least two
      neighboring/overlapping BACs, which represent 315 distinct regions. The average
      size of the sequence polymorphisms was approximately 350 kb and involved in total
      approximately 117 Mb or approximately 3.5% of the genome. Gains were about four
      times more common than deletions, and segmental duplications (SDs) were
      overrepresented, especially in larger deletion variants. This strengthens the
      notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of
      the identified autosomal rearrangements match previously reported CNVs,
      recognized with various platforms. However, results from chromosome X do not
      agree well with the previously annotated CNVs. Furthermore, data from single BACs
      deviating in copy number suggest that our above estimate of total variation is
      conservative. This report contributes to the establishment of the common baseline
      for CNV, which is an important resource in human genetics.

PMID- 18058797
TI  - The expression of low molecular weight protein tyrosine phosphatase is up
      regulated in 1,2-dimethylhydrazine-induced colon tumours in rats.
AB  - Recent studies have assessed the role of low molecular weight protein tyrosine
      phosphatase (LMW-PTP) in cell transformation and tumour onset and progression,
      observing a significant increase in the expression of LMW-PTP mRNA and protein in
      human breast, colon, bladder and kidney tumour samples. Moreover, its enhanced
      expression is generally prognostic of a more aggressive cancer. To better
      understand the role of this protein during colon carcinogenesis and to study
      whether its overexpression is also observed in earlier phases of carcinogenesis,
      we studied its expression in colon tumours, induced in rats by treatment with 1,2
      dimethylhydrazine (DMH), an animal model that resemble the sequential formation
      of histopathological lesions of spontaneous carcinogenesis in humans. The results
      show a significant increase in LMW-PTP expression in adenocarcinomas, suggesting
      that this phenomenon is associated with the onset of malignancy. Moreover a
      significant overexpression of LMW-PTP transcript is associated with tumours
      originating in the proximal (right) part of the colon, confirming an observation
      already reported for human colon cancer.

PMID- 18058798
TI  - Tissue factor expression correlates with disease-specific survival in patients
      with node-negative muscle-invasive bladder cancer.
AB  - Tissue factor (TF), a transmembrane glycoprotein responsible for initiating the
      extrinsic pathway of blood coagulation plays a key role in cancer growth,
      metastasis and angiogenesis. Various studies have demonstrated the prognostic
      potential of TF expression in several cancers. However, its role in bladder
      cancer is unclear. This study evaluated the prognostic potential of TF expression
      in muscle-invasive bladder tumors from patients treated with radical
      cystectomies. Immunohistochemical staining using a monoclonal antibody (mAb) anti
      TF was carried out on sections of tissue microarray blocks containing cores of
      muscle-invasive bladder tumors (4 cores/tumor) from 218 patients. The intensity
      of the staining was evaluated on a scale from 0 to 3 by two independent observers
      who were both unaware of the clinicopathological characteristics of the samples.
      TF was expressed in 77.6% of tumors, independently from baseline characteristics
      (age, gender, stage and grade) as assessed using the chi(2) and Student t tests.
      During follow-up (median: 2.6 years), 45.4% of the patients died from the
      progression of their cancer. Kaplan-Meier survival showed that among the 103
      patients with node-negative (N0) transitional cell carcinoma (TCC), those with TF
      positive tumors had shorter bladder cancer-specific survival (p = 0.0276).
      Moreover, multivariate Cox regression analysis showed they had a 3.15-fold
      greater risk of dying from bladder cancer (95% CI: 1.1-9.0; p = 0.032). In
      conclusion, TF expression was an independent predictor of disease-specific
      survival in N0 muscle-invasive TCCs treated by radical cystectomy and therefore,
      might help identify patients at higher risk of disease progression. These
      patients could potentially benefit from adjuvant chemotherapy.

PMID- 18058799
TI  - Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and
      apoptosis in human colorectal cancer cells.
AB  - 6-Gingerol, a natural product of ginger, has been known to possess anti
      tumorigenic and pro-apoptotic activities. However, the mechanisms by which it
      prevents cancer are not well understood in human colorectal cancer. Cyclin D1 is
      a proto-oncogene that is overexpressed in many cancers and plays a role in cell
      proliferation through activation by beta-catenin signaling. Nonsteroidal anti
      inflammatory drug (NSAID)-activated gene-1 (NAG-1) is a cytokine associated with
      pro-apoptotic and anti-tumorigenic properties. In the present study, we examined
      whether 6-gingerol influences cyclin D1 and NAG-1 expression and determined the
      mechanisms by which 6-gingerol affects the growth of human colorectal cancer
      cells in vitro. 6-Gingerol treatment suppressed cell proliferation and induced
      apoptosis and G(1) cell cycle arrest. Subsequently, 6-gingerol suppressed cyclin
      D1 expression and induced NAG-1 expression. Cyclin D1 suppression was related to
      inhibition of beta-catenin translocation and cyclin D1 proteolysis. Furthermore,
      experiments using inhibitors and siRNA transfection confirm the involvement of
      the PKCepsilon and glycogen synthase kinase (GSK)-3beta pathways in 6-gingerol
      induced NAG-1 expression. The results suggest that 6-gingerol stimulates
      apoptosis through upregulation of NAG-1 and G(1) cell cycle arrest through
      downregulation of cyclin D1. Multiple mechanisms appear to be involved in 6
      gingerol action, including protein degradation as well as beta-catenin,
      PKCepsilon, and GSK-3beta pathways.

PMID- 18058800
TI  - Aberrant expression and localization of connexin43 and connexin30 in a rat glioma
      cell line.
AB  - Gap junctions are cellular structures which permit direct exchanges of small
      molecules from cytoplasm to cytoplasm in most of the cells of metazoan organisms.
      For four decades, it has been observed that the inhibition of this type of
      intercellular communication is often associated with tumorigenesis. The
      assumption that loss of homeostasis which characterizes tumor growth could be a
      consequence of a lack of gap junctional intercellular communication (GJIC) has
      been reinforced by strategies able to reinduce both GJIC and normalization of the
      phenotype. So far, no molecular data may explain clearly how gap junctions can
      regulate cell proliferation. It has been argued that the gap-junction tumor
      suppressive effect may depend specifically on the connexin type which is
      expressed. For instance, the transfection of connexin30 (Cx30), a gap junction
      protein, has been previously associated with a slower growth of rat glioma cells
      (9L cells). Here, we show that these cells do communicate less compared to the
      Cx43-expressing parental cells even if the Cx30-transfected cells do express more
      Cx43. This result was related to the cytoplasmic distribution of Cx43 and a
      nuclear localization of both the Cx30 and a 20-kDa fragment corresponding to a
      Cx43 signal. According to these data, it seems that cell growth regulation may
      depend more on the behavior of connexins than the simple establishment of GJIC.

PMID- 18058801
TI  - The inhibitory effect of connexin 32 gene on metastasis in renal cell carcinoma.
AB  - We have previously reported that connexin (Cx) 32 gene, a member of gap
      junctions, was specifically downregulated in human renal cell carcinoma (RCC) and
      it acts as a tumor suppressor against RCC. Because there is no standard therapy
      for advanced RCC, we investigated the anti-metastatic effect of Cx32 to seek a
      possibility of new RCC therapy. In this study, we used human metastatic RCC cell
      (Caki-1), and established Cx32-expressed cell clone (Caki-1T) or only mock
      transfected cell clone (Caki-1W). For experimental production of metastases, the
      cells were injected into the lateral tail vein of SCID mice. Seventy days after
      inoculation, metastatic colonies were observed in Caki-1W inoculated group,
      though none of them were in Caki-1T inoculated group. The plasma VEGF
      concentration was significantly lower in Caki-1T group compared to Caki-1W group.
      To investigate where Cx32 effects on, we also tried in vitro analysis and found
      that the malignant phenotypes involving metastasis steps were significantly
      decreased in Caki-1T under hypoxia, a mimic condition of internal tumor
      environment. After hypoxia treatment, the protein level of HIF-2alpha, which
      plays main role for hypoxia adaptation, was observed to increase in Caki-1W,
      whereas no expression was observed in Caki-1T. We investigated the activation of
      Src, which is required for stabilization of HIF-2alpha, is suppressed in Caki-1T
      compared to Caki-1W. These results suggest that Cx32 inhibits hypoxia adaptation
      governed by HIF-2alpha, and this may help to reduce the metastasis of RCC cells.

PMID- 18058802
TI  - Identification of polymorphisms in the Caspase-3 gene and their association with
      lung cancer risk.
AB  - Caspase-3 (CASP-3) is a primary effector CASP that executes programmed cell
      death, and it plays an important role in the development and progression of
      cancer. Polymorphisms in the CASP-3 gene may influence CASP-3 production and/or
      activity, thereby modulating the susceptibility to lung cancer. To test this
      hypothesis, we first screened for polymorphisms in the CASP-3 gene by direct
      sequencing of genomic DNA samples from 27 healthy Koreans, and then evaluated
      their associations with lung cancer in a case-control study that consisted of 582
      lung cancer patients and 582 healthy controls. Individuals with at least one
      variant allele of the -928A > G, 77G > A, and 17532A > C polymorphisms were at a
      significantly decreased risk for lung cancer in comparison to the carriers with
      each homozygous wild-type allele [adjusted odds ratio (OR) = 0.79, 95% confidence
      interval (CI) = 0.62-1.00, P = 0.05; adjusted OR = 0.78, 95% CI = 0.61-0.99, P =
      0.04; and adjusted OR = 0.74, 95% CI = 0.58-0.95, P = 0.02, respectively].
      Consistent with the results of genotyping analysis, the GAGC haplotype carrying
      the variant allele at all of the -928A > G, 77G > A, and 17532A > C loci was
      associated with a significantly decreased risk of lung cancer compared to the
      AGGA haplotype carrying no variant alleles at the three loci (adjusted OR = 0.66,
      95% CI = 0.51-0.86, P = 0.002 and Bonferroni corrected P = 0.008). These results
      suggest that the CASP-3 polymorphisms and their haplotypes contribute to the
      genetic susceptibility to lung cancer.

PMID- 18058803
TI  - Novel synthetic triterpenoid methyl 25-hydroxy-3-oxoolean-12-en-28-oate induces
      apoptosis through JNK and p38 MAPK pathways in human breast adenocarcinoma MCF-7
      cells.
AB  - Breast cancer is the most common neoplasm in women and is the leading cause of
      cancer-related death for women. Therefore, new agents targeting prevention and
      treatment of breast cancer are urgently needed. The present study first
      investigates that a novel triterpenoid Methyl 25-Hydroxy-3-oxoolean-12-en-28-oate
      (AMR-Me) derived from 25-Hydroxy-3-oxoolean-12-en-28-oic acid (AMR) is a potent
      inhibitor of cell growth by inducing human breast cancer MCF-7 cells to undergo
      apoptosis. AMR-Me induced DNA fragmentation and PARP degradation which were
      preceded by changing Bax/Bcl-2 ratios, cytochrome c release, and subsequent
      induction of pro-caspase-9 and -7 processing in breast carcinoma MCF-7 cells, but
      it did not act on Fas/Fas ligand pathways and the activation of caspase-8,
      suggesting AMR-Me triggered the mitochondrial apoptotic pathway. The general
      caspase blocking peptide VAD partially blocked AMR-Me induced apoptosis. AMR-Me
      stimulated p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase
      (JNK), but not extracellular signal-regulated kinase activation during apoptosis.
      SP600125, a specific inhibitor for JNK and SB203580, a p38 MAPK-specific
      inhibitor suppressed AMR-Me induced apoptosis indicating that activation of JNK
      and p38 MAPKs involved in the mitochondrial activation-mediated cell death
      pathway. Our results suggest that AMR-Me can utilize two different MAPK signaling
      pathways for amplifying the apoptosis cascade, is critical for both our
      understanding of cell death events and development of cancer
      preventive/therapeutic agents.

PMID- 18058804
TI  - Involvement of JNK/p73/NOXA in vitamin E analog-induced apoptosis of human breast
      cancer cells.
AB  - Microarray analyses of human MDA-MB-435 breast cancer cells treated with vitamin
      E analog 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl) chroman-6-yloxy
      acetic acid (alpha-TEA) showed over 400 genes to be modulated. Thirty-four genes
      deemed of interest based on potential involvement in anticancer activities of
      alpha-TEA fell into six categories: apoptosis related, signal transduction, cell
      cycle related, cell adhesion and motility, transcriptional regulators, and
      membrane traffic related. The gene (PMAIP1) for NOXA was studied further. NOXA
      mRNA and protein levels were elevated in a time and dose-dependent fashion
      following alpha-TEA treatment. Functional knockdowns using small interfering RNA
      (siRNA) showed NOXA to contribute to alpha-TEA-induced apoptosis. A correlation
      between alpha-TEA's ability to upregulate NOXA and induce apoptosis was seen
      among several human breast cancer cell lines. Efforts to identify upstream
      regulators of NOXA in alpha-TEA-induced apoptosis identified the necessity of
      both c-Jun N-terminal kinase (JNK) activation and p73 expression. Additionally,
      protein levels of full length p73 were decreased by JNK siRNA treatment,
      suggesting that the signal transduction module of JNK-p73-NOXA is involved in
      alpha-TEA induced apoptosis of human breast cancer cells. Taken together, these
      findings suggest a role for JNK activation in mediating full length p73
      expression and add to our understanding of the mechanisms of anticancer actions
      of alpha-TEA, a potential chemotherapeutic agent.

PMID- 18058805
TI  - Modified expression of cytoplasmic isocitrate dehydrogenase electrophoretic
      isoforms in seminal plasma of men with sertoli-cell-only syndrome and seminoma.
AB  - Two isoforms of human cytoplasmic isocitrate dehydrogenase (IDPc) of close
      molecular weights and different isoelectric points were identified in human
      seminal plasma (SP) by two-dimensional gel electrophoresis (2-DE) followed by
      mass spectrometry (MS). These two isoforms were detected in the normospermic men
      SP and their expressions were markedly altered in patients with testicular
      seminoma, the most frequent testicular germ cell cancer (TGCC): increase of the
      more acidic spot and decrease of the more basic one. Since oligospermia has been
      considered as a high risk pathological condition for developing a testicular
      cancer, the two IDPc isoforms were analyzed in SP of a group of secretory
      azoospermic patients. In this group the two spots displayed similar variations of
      expression to those observed in testicular seminoma. These results propose IDPc
      as a promising SP biomarker of testicular seminoma. Whether IDPc alteration in
      secretory azoospermia is predictive of testicular seminoma remains to be
      elucidated.

PMID- 18058806
TI  - Expression of an activated mammalian target of rapamycin in adenocarcinoma of the
      cervix: A potential biomarker and molecular target therapy.
AB  - Alterations of the Akt/mTOR pathway have been observed in numerous types of
      cancer, thus this pathway represents an exciting new target for molecular
      therapeutics. We investigated the expression of activated Akt (p-Akt) and mTOR (p
      mTOR) in patients with adenocarcinoma of the cervix and the involvement of the p
      Akt/p-mTOR pathway in response to combination of inhibitor agents, rapamycin and
      LY294002, with conventional therapy, cisplatin, in vitro. Immunohistochemistry
      analysis of p-Akt and p-mTOR was conducted in 26 patients with adenocarcinoma of
      the cervix. Western blot analysis was performed to determine the protein
      expression involved in response to chemotherapy in cervical cancer cell lines.
      The results showed that p-Akt and p-mTOR were identified in 50% and 53.8% of
      adenocarcinoma of the cervix. The expression of p-mTOR was a significant
      independent marker for prognosis. A significant correlation between p-Akt and p
      mTOR was observed. There was no correlation between their expressions with any of
      clinicopathological factors. In the in vitro study, cisplatin at CPI(50) targets
      both the apoptosis and survival pathway by activating the caspase-cascade;
      inhibiting Akt, mTOR, p70S6K, and 4EBP1. Combination of rapamycin with cisplatin
      induced synergistic interaction. On the other hand, combination with LY294002
      resulted in either synergistic or antagonistic effect depending on the doses
      given. Rapamycin pretreatment potentiated cisplatin-induced apoptosis cell death
      and enhanced blocking of the survival pathway. Overall, the expression of p-mTOR
      is a significant prognostic marker of adenocarcinoma of the cervix and a
      potential molecular target for the treatment of cervical cancer. Inhibition of
      the mTOR pathway contributes to cisplatin-induced apoptosis in cervical cancer
      cell lines.

PMID- 18058807
TI  - Interrelationships between dietary restriction, the IGF-I axis, and expression of
      vascular endothelial growth factor by prostate adenocarcinoma in rats.
AB  - Human studies suggest that excessive energy intake and obesity may influence
      prostate cancer progression. Rodent experiments demonstrate that diet restriction
      attenuates tumor growth in parallel with reduced vascular density. The present
      study examines changes in the insulin-like growth factor I (IGF-I) axis caused by
      dietary restriction and their association with the expression of vascular
      endothelial growth factor (VEGF) in prostate cancer. Weanling male Copenhagen
      rats were randomized into control or 40% dietary restricted groups (n = 5). After
      8 wk, rats were implanted with rat AT6.3 prostate adenocarcinoma cells. Two weeks
      later, the animals were sacrificed and serum, normal prostate, liver, and
      prostate tumor samples were collected for analyses. Dietary restriction reduced
      serum concentrations of IGF-I by 35% (P < 0.05) and increased IGF-binding protein
      3 (IGFBP3) by sevenfold (P < 0.0001). Lower circulating IGF-I concentrations were
      correlated with reduced IGF-I mRNA expression in the liver, the primary source of
      circulating IGF-I. Dietary restriction also lowered mRNA expression of IGF-I
      (45%, P = 0.0242) and its receptor IGFIR (40%, P = 0.0083) in prostate tumors.
      Similarly, reduced VEGF mRNA (30%, P = 0.0176) and secreted VEGF protein (33%, P
      = 0.0003) were observed in prostate cancer of restricted rats. An in vitro study
      employing AT6.3 prostate cancer cells demonstrated dose- and time-dependent
      stimulation of VEGF expression by IGF-I. These results suggest that dietary
      restriction reduces endocrine and prostate tumor autocrine/paracrine IGF-I
      expression, which contributes to reduced VEGF expression and signaling, to
      inhibit tumor angiogenesis associated with prostate tumorigenesis.

PMID- 18058808
TI  - 15-Hydroxyprostaglandin dehydrogenase suppresses K-RasV12-dependent tumor
      formation in Nu/Nu mice.
AB  - Oncogenic Ras mutations are early genetic events in colorectal cancer that induce
      cyclooxygenase (COX)-2 expression and prostaglandin E(2) (PGE(2)) biosynthesis.
      PGE(2), a downstream product of COX-2, promotes cancer progression by modulating
      proliferation, apoptosis and angiogenesis. 15-hydroxyprostaglandin dehydrogenase
      (PGDH) degrades PGE(2) and is down-regulated in colorectal cancer, suggesting
      that PGDH plays a role in regulating PGE(2) levels and that PGDH over-expression
      could attenuate Ras-mediated tumorigenesis. Lentiviral transduction was used to
      express GFP (18.GFP), K-Ras(V12) (18.K-Ras(V12)), PGDH (18.PGDH) or both K
      Ras(V12) and PGDH (18.K-Ras(V12).PGDH) in nontumorigenic rat intestinal
      epithelial (IEC-18) cells. 18.K-Ras(V12) cells exhibited increased
      phosphorylation of MAP kinases and CREB, proliferation rates, COX-2 and
      microsomal prostaglandin E synthase (mPGES)-1 expression and PGE(2) and PGI(2)
      levels. 18.PGDH and 18.K-Ras(V12).PGDH cells had 10(4)-fold increases in PGDH
      activity with decreased PGE(2) and PGI(2) levels, COX-2 and mPGES-1 expression
      and proliferation rates. 18.GFP, 18.PGDH, and 18.K-Ras(V12).PGDH cells were
      unable to grow in soft agar media whereas 18.K-Ras(V12) cells exhibited anchorage
      independent cell growth. Xenografts of implanted 18.K-Ras(V12) cells in nu/nu
      mice produced rapid (2 wk) tumors with uniform antibody staining for COX-2 and
      mPGES-1 throughout the tumor and elevated PGE(2) levels. Xenografts of 18.K
      Ras(V12).PGDH cells exhibited delayed (8 wk) tumor formation with negligible COX
      2 and mPGES-1 expression and significantly decreased PGE(2) levels. 18.K
      Ras(V12).PGDH tumors had decreased staining of the proliferative marker, Ki-67,
      and a significant increase in apoptosis in the central region of the tumor. Based
      on these data, we conclude that PGDH expression suppresses K-Ras(V12)-mediated
      tumorigenesis in intestinal epithelial cells.

PMID- 18058809
TI  - Absolute lymphocyte count is a novel prognostic indicator in ALL and AML:
      implications for risk stratification and future studies.
AB  - BACKGROUND: Leukemia is the leading cause of disease-related death in children,
      despite significant improvement in survival and modern risk stratification. The
      prognostic significance of absolute lymphocyte counts (ALC) was evaluated in
      young patients with acute myeloblastic leukemia (AML) and acute lymphoblastic
      leukemia (ALL). METHODS: In all, 171 consecutive de novo cases of AML and ALL,
      age <or=21 years, were analyzed. Age, initial white blood cell count,
      cytogenetics, and bone marrow response were compared with lymphocyte, neutrophil,
      and platelet counts at weekly intervals during induction chemotherapy. RESULTS:
      ALC is a significant independent predictor of relapse and survival. For example,
      in patients with AML an ALC on Day 28 of induction (ALC-28) <350 cells/microL
      predicts very poor survival, with a 5-year relapse-free survival (RFS) of only
      10% (hazard ratio [HR] 3.7, P= .003). In contrast, an ALC-15 >350 cells/microL
      carries an excellent prognosis, with a 5-year overall survival (OS) of 85% (HR
      0.2, P= .012). Similarly in ALL, an ALC-15 <350 cells/microL predicts poor
      survival, with a 6-year RFS of 43% (HR 4.5, P= .002), whereas an ALC-15 >350
      cells/microL predicts excellent outcome, with a 6-year OS of 87% (HR 0.2, P=
      .018). Importantly, ALC remains a strong predictor in multivariate analysis with
      known prognostic factors. CONCLUSIONS: ALC is a simple, statistically powerful
      measurement for patients with de novo AML and ALL. The results, when combined
      with previous studies, demonstrate that ALC is a powerful new prognostic factor
      for a range of malignancies. These findings suggest a need for further
      exploration of postchemotherapy immune status and immune-modulating cancer
      therapies.

PMID- 18058810
TI  - A prospective randomized trial of thalidomide with topotecan compared with
      topotecan alone in women with recurrent epithelial ovarian carcinoma.
AB  - BACKGROUND: Thalidomide is an antiangiogenic agent with immune modulating
      potential. The objective of this study was to determine response rates among
      women who were treated for recurrent ovarian cancer using topotecan with or
      without thalidomide. METHODS: Women were enrolled in this multicenter,
      prospective, randomized phase 2 trial between April 2001 and July 2005. Eligible
      patients had recurrent epithelial ovarian carcinoma with measurable disease or
      elevated CA 125 values. Patients had received prior platinum-based chemotherapy.
      Treatment arms received topotecan at a dose of 1.25 mg/m(2) on Days 1 through 5
      of a 21-day cycle with or without thalidomide starting at a dose of 200 mg per
      day and then increasing the dose as tolerated. Toxicity was graded according to
      the National Cancer Institute Common Toxicity Criteria. The chi-square test was
      used to assess differences in response and toxicity, and the log-rank test was
      used to compare Kaplan-Meier survival curves. RESULTS: The analysis included 69
      women (39 women in the control arm and 30 women in the thalidomide arm). Known
      prognostic factors, including platinum sensitivity, were represented equally in
      each arm. The median thalidomide dose was 200 mg per day. The overall response
      rate in the control arm was 21% (complete response [CR] rate, 18%; partial
      response [PR] rate, 3%) compared with 47% in the thalidomide arm (CR rate, 30%;
      PR rate, 17%) (P= .03). The median progression-free survival for the control arm
      was 4 months compared with 6 months in the thalidomide arm (P= .02). The median
      overall survival was 15 months in the control arm and 19 months in the
      thalidomide arm (P= .67). Toxicities were similar between groups. CONCLUSIONS:
      The addition of thalidomide to topotecan for the treatment of recurrent ovarian
      cancer appears to improve response rates, and the authors believe that it
      warrants study through larger phase 3 trials.

PMID- 18058811
TI  - Messenger RNA expression patterns of histone-associated genes in bovine
      preimplantation embryos derived from different origins.
AB  - Histone modification genes in bovine embryos: The mRNA expression pattern of
      histone-related genes was determined in bovine oocytes and embryos. We compared
      immature and in vitro-matured oocytes, either before or after enucleation and
      activation, in vitro produced embryos (zygotes, 8-16 cell stages, blastocysts),
      embryos cloned with female or male donor cells; parthenogenetic embryos, and in
      vivo-derived blastocysts to detect deviations from the normal expression pattern.
      A sensitive semi-quantitative endpoint RT-PCR assay was used to reveal
      differences in histone deacetylation [histone deacetylase 2 (HDAC2)]; histone
      acetylation [histone acetyltransferase 1 (HAT1)]; histone methylation [histone
      methyltransferases (SUV39H1, G9A)]; heterochromatin formation [heterochromatin
      protein 1 (HP1)]; and chromatin-mediated transcription regulation [zygote arrest
      1 (ZAR1)]. With the exception of ZAR1, these mRNAs were present throughout
      preimplantation development. The relative abundance of mRNAs for histone
      methyltransferases (SUV39H1 and G9A) and for heterochromatin-associated protein
      (HP1) differed significantly before and after activation of the bovine embryonic
      genome. The similarity of HAT1 gene expression in 8-16 cell embryos and
      blastocysts suggests that histone acetylation is primarily affected by in vitro
      culture only prior to embryonic genome activation. HDAC2 gene mRNA expression was
      not affected by in vitro culture and/or cloning before and after activation of
      the embryonic genome. The donor cell line affected mRNA expression patterns of
      genes involved in reprogramming cloned embryos suggesting epigenetic
      dysregulation. Results show that both in vitro production and somatic cloning
      alter the mRNA expression of histone modifying genes in bovine embryos.

PMID- 18058812
TI  - Quantitative, spatial resolution of the epigenetic field effect in prostate
      cancer.
AB  - BACKGROUND: Although a field effect in which transformed cells extend beyond
      morphologically evident tumor has been proposed in cancer, little direct evidence
      exists as to its magnitude and spatial resolution. We tested this hypothesis
      using molecular techniques to detect epigenetic changes in the primary tumor and
      surrounding tissues. METHODS: Ex vivo core biopsies, each spaced approximately 1
      mm apart, were generated from 37 unique prostatectomy samples. The first core
      biopsy was confirmed to be histologically positive for cancer, and the subsequent
      biopsies were confirmed to be histologically negative. The methylation ratio of
      GSTP1, APC, RARbeta2, and RASSF1A were measured for all of the 159 cores.
      RESULTS: No field effect, defined as absence of epigenetically transformed cells,
      for GSTP1 was observed whereas APC, RARbeta2, and RASSF1A showed a field effect
      up to 3 mm from the malignant core in three prostatectomy samples. Furthermore,
      for each case, different patterns of the field effect were observed. The field
      effect appeared most pronounced with RARbeta2. In 11 prostatectomy samples in
      which a second focus of cancer was identified, cells harboring RARbeta2
      methylation extended a large distance away from the primary tumor in one sample.
      Bisulfite sequencing of RARbeta2 confirmed the presence of epigenetic
      aberrations. CONCLUSIONS: This study quantifies previous observations of
      methylation in histologically negative samples and provides important assessment
      of field effects based on epigenetic events in cancer. These molecular approaches
      set the stage for consideration of such data in prospective trials for assessment
      of surgical margins and prediction of recurrence.

PMID- 18058813
TI  - Partner-matching for the automated identification of reproducible ICA components
      from fMRI datasets: algorithm and validation.
AB  - The analysis of functional magnetic resonance imaging (fMRI) data is complicated
      by the presence of a mixture of many sources of signal and noise. Independent
      component analysis (ICA) can separate these mixtures into independent components,
      each of which contains maximal information from a single, independent source of
      signal, whether from noise or from a discrete physiological or neural system. ICA
      typically generates a large number of components for each subject imaged,
      however, and therefore it generates a vast number of components across all of the
      subjects imaged in an fMRI dataset. The practical implementation of ICA has been
      limited by the difficulty in discerning which of these many components are
      spurious and which are reproducible, either within or across individuals of the
      dataset. We have developed a novel clustering algorithm, termed "Partner
      Matching" (PM), which identifies automatically the independent components that
      are reproducible either within or between subjects. It identifies those
      components by clustering them according to robust measures of similarity in their
      spatial configurations either across different subjects of an fMRI dataset,
      within a single subject scanned across multiple scanning sessions, or within an
      individual subject scanned across multiple runs within a single scanning session.
      We demonstrate the face validity of our algorithm by applying it to the analysis
      of three fMRI datasets acquired in 13 healthy adults performing simple auditory,
      motor, and visual tasks. From among 50 independent components generated for each
      subject, our PM algorithm automatically identified, across all 13 subjects,
      components representing activity within auditory, motor, and visual cortices,
      respectively, as well as numerous other reproducible components outside of
      primary sensory and motor cortices, in functionally connected circuits that
      subserve higher-order cognitive functions, even in these simple tasks.

PMID- 18058814
TI  - Predictors of prognosis in patients with olfactory disturbance.
AB  - OBJECTIVE: Although olfaction is often compromised by such factors as head
      trauma, viruses, and toxic agents, the olfactory epithelium and sectors of the
      olfactory bulb have the potential for regeneration. This study assessed the
      degree to which olfactory function changes over time in patients presenting to a
      university-based smell and taste center with complaints of olfactory dysfunction
      and the influences of etiology (eg, head trauma, upper respiratory infection),
      sex, age, smoking behavior, degree of initial dysfunction, and other factors on
      such change. METHODS: Well-validated odor identification tests were administered
      to 542 patients on 2 occasions separated from one another by 3 months to 24
      years. Multivariable regression and chi2 analyses assessed the influences of the
      variables on the longitudinal changes in olfactory test scores. RESULTS: On
      average, smell test scores improved modestly over time. Patient age, severity of
      initial olfactory loss, and the duration of dysfunction at first testing were
      significant predictors of the amount of the change. Etiology, sex, time between
      the two test administrations, and initial smoking behavior were not significant
      predictors. The percentage of anosmic and microsmic patients exhibiting
      statistically significant change in function was 56.72 and 42.86%, respectively.
      However, only 11.31% of anosmic and 23.31% of microsmic patients regained normal
      age-related function over time. INTERPRETATION: Some recovery can be expected in
      a significant number of patients who experience smell loss. The amount of
      recovery depends on the degree of initial loss, age, and the duration of loss.
      Etiology, per se, is not a significant determinant of prognosis, in contrast with
      what is commonly believed.

PMID- 18058815
TI  - The histone acetyltransferase hMOF is frequently downregulated in primary breast
      carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in
      medulloblastoma.
AB  - Loss of H4 lysine 16 (H4K16) acetylation was shown to be a common feature in
      human cancer. However, it remained unclear which enzyme is responsible for the
      loss of this modification. Having recently identified the histone
      acetyltransferase human MOF (hMOF) to be required for bulk H4K16 acetylation,
      here we examined the involvement of hMOF expression and H4K16 acetylation in
      breast cancer and medulloblastoma. Analysis of a recent mRNA expression profiling
      study in breast cancer (n = 100 cases) and an array-CGH screen in
      medulloblastomas (n = 102 cases), revealed downregulation in 40% and genomic loss
      in 11% of cases, respectively. We investigated hMOF protein expression as well as
      H4K16 acetylation in large series of primary breast carcinomas (n = 298) and
      primary medulloblastomas (n = 180) by immunohistochemistry. In contrast to
      nontransformed control tissues, significant fractions of both primary breast
      carcinomas and medulloblastomas showed markedly reduced hMOF mRNA and protein
      expression. In addition, hMOF protein expression tightly correlated with
      acetylation of H4K16 in all tested samples. For medulloblastoma, downregulation
      of hMOF protein expression was associated with lower survival rates identifying
      hMOF as an independent prognostic marker for clinical outcome in univariate as
      well as multivariate analyses.

PMID- 18058816
TI  - Marked regression of liver metastasis by combined therapy of ultrasound-mediated
      NF kappaB-decoy transfer and transportal injection of paclitaxel, in mouse.
AB  - Nuclear factor-kappaB (NF kappaB) plays a pivotal role in cancer progression. In
      this study, we developed a decoy cis-element oligo-deoxyribonucleic acid against
      NF kappaB-binding site (NF kappaB-decoy), which effectively inhibits NF kappaB
      activity, and tested the effect of combined therapy comprising local transfection
      of NF kappaB-decoy into the liver and transportal injection of paclitaxel on
      cancer growth and metastasis using an orthotopic murine model of colon cancer
      liver metastasis. For NF kappaB-decoy transfection, we employed a novel approach
      using ultrasound exposure with an echocardiographic contrast agent, Optison. We
      examined the influence of NF kappaB-decoy transfer on susceptibility to
      paclitaxel in cancer cells and the mechanism involved using several in vitro
      analysis systems. We then studied the in vivo effect of combined NF kappaB-decoy
      transfer and paclitaxel in preventing cancer progression using a murine model of
      liver metastasis created by splenic injection of a human colon cancer cell line,
      HT29. In vitro experiments, including MTT-assay, fluorescence-activated cell
      sorter and cDNA array analysis, revealed that NF kappaB-decoy transfer
      significantly increased the susceptibility of cancer cells to paclitaxel, and
      that decreased expression of anti-apoptotic genes along with increased expression
      of genes relevant to the apoptosis-promotor may be involved. In vivo experiments
      showed that local transfection of NF kappaB-decoy into the liver followed by
      portal injection of paclitaxel effectively induced cancer cell apoptosis in the
      liver metastasis, and significantly prolonged animal survival compared to
      controls, without notable side effects. In conclusion, a combination of local NF
      kappaB-decoy transfer into the liver and transportal injection of paclitaxel may
      be a safe and effective new therapy for liver metastasis.

PMID- 18058817
TI  - Serous ovarian, fallopian tube and primary peritoneal cancers: a comparative
      epidemiological analysis.
AB  - Invasive serous cancers are diagnosed in the ovary, fallopian tube and
      peritoneum. It is widely believed that these are variants of the same malignancy
      but little is known about fallopian tube and primary peritoneal cancers. A
      comparison of risk factors for these tumor types may shed light on common or
      distinct aetiological pathways involved in these types of cancer. We investigated
      risk factors for the three cancers using data from a large Australian population
      based case-control study. We included women with incident invasive serous ovarian
      (n = 627), primary peritoneal (n = 129) and fallopian tube (n = 45) cancer and
      1,508 control women. Participants completed a comprehensive reproductive and
      lifestyle questionnaire. Logistic regression was used to calculate odds ratios
      (ORs) and 95% confidence intervals (CIs). Hormonal contraceptive use was
      inversely related to risk of all three cancers. Parity and breast-feeding were
      also inversely related to risk of serous ovarian and fallopian tube cancer. In
      contrast, parous women had an increased risk of peritoneal cancer (OR = 1.8,
      95%CI 0.8-3.9), and increasing parity did not lower risk. There was also no
      association between breast-feeding and peritoneal cancer. However, obesity was
      associated with a doubling of risk for peritoneal cancer alone (OR = 2.1, 95%CI =
      1.3-3.4). The strikingly similar patterns of risk for serous ovarian and
      fallopian tube cancers and the somewhat different results for primary peritoneal
      cancer suggest that peritoneal cancers may develop along a different pathway.
      These results also call into question the role of the physical effects of
      ovulation in the development of serous ovarian cancer.

PMID- 18058818
TI  - The effects of a COX-2 inhibitor meloxicam on squamous cell carcinoma of the
      esophagus in vivo.
AB  - Our previous study showed that aspirin induced apoptosis of esophageal cancer
      cells in vitro by inhibiting the pathway of NF-kappaB downstream regulation of
      cyclooxygenase-2. The purpose of this study was to determine if similar changes
      occurred in vivo in the tumors of patients with SCC of the esophagus who were
      given a preferential COX-2 inhibitor, meloxicam. Fifty-three patients who had an
      esophagectomy for SCC were allocated randomly to either a Treatment group (n =
      25) or a control group (n = 28). Patients in the Treatment group were given 7.5
      mg/day of meloxicam, for between 10 and 14 days before surgery. Patients in the
      control group did not take any type of NSAID during this time interval. Samples
      of the tumor taken from the resected specimens were collected. Proliferation and
      apoptosis were measured by flow cytometry. The concentration of 6-keto
      prostaglandin F(1)alpha in cancer tissue was determined by radio-immuno-assay.
      Expression of COX-2 mRNA was measured with RT-PCR and COX-2 protein levels with
      Western blot analysis. Nuclear NF-kappaB and cytoplasmic I kappaB protein levels
      were determined by electrophoretic mobility shift assay and Western blot,
      respectively. There were significantly more apoptotic cells in the tumors of
      patients who were using meloxicam. It also decreased the levels of COX-2 mRNA,
      COX-2 protein and nuclear NF-kappaB protein and increased the cytoplasmic I
      kappaB protein in the cancer. We conclude that meloxicam induces apoptosis in SCC
      of the esophagus in vivo by inhibiting the pathway of NF-kappaB downstream
      regulation of COX-2.

PMID- 18058819
TI  - Gene expression abnormalities in histologically normal breast epithelium of
      breast cancer patients.
AB  - Normal-appearing epithelium of cancer patients can harbor occult genetic
      abnormalities. Data comprehensively comparing gene expression between
      histologically normal breast epithelium of breast cancer patients and cancer-free
      controls are limited. The present study compares global gene expression between
      these groups. We performed microarrays using RNA from microdissected
      histologically normal terminal ductal-lobular units (TDLU) from 2 groups: (i)
      cancer normal (CN) (TDLUs adjacent to untreated ER+ breast cancers (n = 14)) and
      (ii) reduction mammoplasty (RM) (TDLUs of age-matched women without breast
      disease (n = 15)). Cyber-T identified differentially expressed genes.
      Quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC), and comparison to
      independent microarray data including 6 carcinomas in situ (CIS), validated the
      results. Gene ontology (GO), UniProt and published literature evaluated gene
      function. About 127 probesets, corresponding to 105 genes, were differentially
      expressed between CN and RM (p < 0.0009, corresponding to FDR <0.10). 104/127
      (82%) probesets were also differentially expressed between CIS and RM, nearly
      always (102/104 (98%)) in the same direction as in CN vs. RM. Two-thirds of the
      105 genes were implicated previously in carcinogenesis. Overrepresented
      functional groups included transcription, G-protein coupled and chemokine
      receptor activity, the MAPK cascade and immediate early genes. Most genes in
      these categories were under-expressed in CN vs. RM. We conclude that global gene
      expression abnormalities exist in normal epithelium of breast cancer patients and
      are also present in early cancers. Thus, cancer-related pathways may be perturbed
      in normal epithelium. These abnormalities could be markers of disease risk,
      occult disease, or the tissue's response to an existing tumor.

PMID- 18058820
TI  - Variants in the neuronal nitric oxide synthase (nNOS, NOS1) gene are associated
      with restless legs syndrome.
AB  - Sixty percent of the patients with restless legs syndrome (RLS) report a positive
      family history. To date five loci have been mapped on chromosome 12q, 14q, 9p,
      2q, and 20p (RLS1-5) but no gene has been identified so far. To identify genes
      related to RLS, we performed a three-stage association study (explorative study,
      replication study, high-density mapping) in two Caucasian RLS case-control
      samples of altogether 918 independent cases and controls. In the explorative
      study (367 cases and controls, respectively), we screened 1536 SNPs in 366 genes
      in a 21 Mb region encompassing the RLS1 critical region on chromosome 12.
      Armitage trend test revealed three genomic regions that were significant (P <
      0.05). In the replication study (551 cases and controls, respectively) we
      genotyped the most significant SNPs of Stage 1. After correction for multiple
      testing, association was observed with SNP rs7977109 (P(nominal) = 0.00175,
      P(Westfall-Young) = 0.04895, OR = 0.76228, 95% CI = 0.64310-0.90355), which is in
      the neuronal nitric oxide synthase (NOS1) gene. High-density mapping using
      altogether 34 tagging and coding SNPs of the NOS1 gene in both case-control
      samples further confirmed the significant association results to NOS1. Ten more
      SNPs revealed significance with nominal P-values from 0.0001 to 0.0482 (genotypic
      test and Armitage test). Altogether, this study provides evidence for an
      association of variants in the NOS1 gene and RLS, and suggests the involvement of
      the NO/arginine pathway in the pathogenesis of RLS. Potential usage of NO
      modulating agents as new treatment options for RLS have become a challenging
      aspect for future research of this disorder.

PMID- 18058821
TI  - Structural basis for the binding of high affinity phosphopeptides to Stat3.
AB  - Signal transducer and activator of transcription 3 (Stat3) is constitutively
      active in a number of cancers where it participates in aberrant transcription of
      prosurvival, cell cycling, and angiogenesis genes. Since Stat3 initiates its
      signaling activity through binding of its SH2 domain to phosphotyrosine residues
      on cell surface receptors, inhibitors targeting this region of the protein are
      potential chemotherapeutic agents. To date, no NMR or X-ray crystallographic
      structures of high-affinity phosphopeptides complexed with the Stat3 SH2 domain
      are available to aid in the development of peptidomimetic antagonists.
      Examination of the crystal structures of several STAT proteins and the complex of
      Stat1 with Ac-pTyr-Asp-Lys-Pro-His-NH(2) led to a hypothesis that the specificity
      determinant for Stat3, glutamine at position pY+3 in pTyr-Xxx-Xxx-Gln sequences,
      resides in a unique pocket on the protein surface at the juncture of the third
      strand of the central beta-sheet and a unique, STAT specific alpha-helix. Docking
      of Ac-pTyr-Leu-Pro-Gln-NHBn to the SH2 domain of Stat3 using molecular modeling
      showed that the Gln binds tightly in this pocket and participates in a network of
      hydrogen bonds. Novel interactions between the peptide main chain and the protein
      were also discovered. Phosphopeptide structure-affinity studies using unnatural
      amino acids and glutamine derivatives provide evidence for the peptide-protein
      interactions revealed by the model and lend support to the binding hypothesis.

PMID- 18058822
TI  - Repetitive induction of late-phase LTP produces long-lasting synaptic enhancement
      accompanied by synaptogenesis in cultured hippocampal slices.
AB  - Long-term plasticity of synaptic transmission is assumed to underlie the
      formation of long-term memory. Although the cellular mechanisms underlying short
      term plasticity have been analyzed in detail, the mechanisms underlying the
      transformation from short-term to long-term plasticity remain largely unrevealed.
      We propose the novel long-lasting phenomenon as a model system for the analysis
      of long-term plasticity. We previously reported that the repetitive activation of
      cAMP-dependent protein kinase (PKA) by forskolin application led to an
      enhancement in synaptic strength coupled with synaptogenesis that lasted more
      than 3 weeks in cultured rat hippocampal slices. To elucidate whether this long
      lasting synaptic enhancement depended on the induction of long-term potentiation
      (LTP) or on the pharmacological effect of forskolin, we applied glutamate (Glu)
      and correlated its dose with the production of the long-lasting synaptic
      enhancement. When the dose of Glu was low (10, 30 muM), only transient excitation
      or early-phase LTP (E-LTP) was induced by a single application and no long
      lasting synaptic enhancement was produced by three applications. When the dose
      was raised to 100 or 300 muM, late-phase LTP (L-LTP) was induced by a single
      application and long-lasting synaptic enhancement was produced by three
      applications. The Glu-produced enhancement was accompanied by an increase in the
      frequency (but not the amplitude) of miniature EPSC and the number of synaptic
      structures. The enhancement depended on the interval of repetition and protein
      synthesis immediately after the Glu applications. These results indicate that the
      repetitive induction of L-LTP, but not E-LTP or transient excitation, triggers
      cellular processes leading to the long-lasting synaptic enhancement and the
      formation of new synapses.

PMID- 18058824
TI  - The MeCP2-null mouse hippocampus displays altered basal inhibitory rhythms and is
      prone to hyperexcitability.
AB  - Rett syndrome is an autism-spectrum disorder caused by loss of function mutations
      within the gene encoding methyl CpG-binding protein 2 (MeCP2). While subtle
      decreases in synaptic plasticity have been detected within cortical and
      hippocampal neurons of Mecp2-null mice, only minimal information exists regarding
      how the loss of MeCP2 affects network activity in the brain. To address this
      issue, we compared the intrinsic network activities of Mecp2-null hippocampal
      slices derived from symptomatic mice to wild-type slices. Extracellular and whole
      cell patch recordings revealed that although spontaneous, IPSP-based rhythmic
      activity is present in Mecp2-null slices; its frequency is significantly reduced
      from wild-type. This reduction was not associated with alterations in the gross
      electrophysiological properties of hippocampal neurons, but was associated with a
      decreased level of spontaneous glutamate receptor-mediated synaptic currents in
      hippocampal CA3 neurons. Paradoxically, however, repetitive sharp wave-like
      discharges were readily induced in the Mecp2-null hippocampal slices by a brief
      train of high-frequency stimulation commonly used to establish long-term
      potentiation at wild-type slices. Taken together, our data indicate that the
      Mecp2-null hippocampal CA3 circuit has diminished basal inhibitory rhythmic
      activity, which in turn renders the circuitry prone to hyperexcitability.

PMID- 18058823
TI  - Different behavioral effects of neurotoxic dorsal hippocampal lesions placed
      under either isoflurane or propofol anesthesia.
AB  - Anesthetic protocols for behavioral neuroscience experiments are evolving as new
      anesthetics are developed and surgical procedures are refined to improve animal
      welfare. We tested whether neurotoxic dorsal hippocampal lesions produced under
      two different anesthetic protocols would have different behavioral and/or histo
      pathological effects. Rats were anesthetized with either propofol, an intravenous
      anesthetic, or isoflurane, a gaseous anesthetic, and multiple injections of an
      excitotoxin (N-methyl-D-aspartate) were stereotaxically placed in the dorsal
      hippocampus bilaterally. Intraoperative physiological parameters were similar in
      the two surgical groups, as were the volumes of the lesions, although the profile
      of postoperative impairment in a spatial learning task differed between the
      lesion groups depending on the anesthetic regimen used. These results show that
      the choice of anesthetic protocol is a critical variable in designing behavioral
      neuroscience experiments using neurosurgical procedures. This factor should be
      considered carefully in experimental design and in cross-study comparisons of
      lesion effects on behavior.

PMID- 18058825
TI  - An ultrastructural characterization of the newly generated cells in the adult
      monkey dentate gyrus.
AB  - Recent studies of adult neurogenesis in the hippocampus have focused on the
      maturational sequence and on the identification of the neural stem cell in the
      adult brain. Ultrastructural verification of cell type and marker expression has
      become increasingly important in this research, yet no standards exist for the
      identification of adult generated cells in the hippocampus. In this study, six
      adult rhesus monkeys were used, four of which were given an injection of the DNA
      synthesis phase marker bromodeoxyuridine (BrdU) and perfused 2 days, 3 weeks, or
      6 weeks later. The ultrastructural features of BrdU labeled cells in the dentate
      gyrus were determined. The characteristics of the different types of BrdU labeled
      cells were then used to find similar, but unlabeled, immature cells in tissue
      routinely prepared for electron microscopy. This enabled optimal characterization
      of the ultrastructural features of the newly generated cells. The results
      demonstrate that immature neurons, immature astrocytes, and oligodendrocyte
      progenitor cells can be reliably distinguished by ultrastructural features,
      without immunohistochemical processing.

PMID- 18058826
TI  - Voltage-induced morphological modifications in oocyte membranes containing
      exogenous K+ channels studied by electrochemical scanning force microscopy.
AB  - We report on a novel use of electrochemical scanning force microscopy (SFM) for
      the investigation of morphological modifications occurring in plasma membranes
      containing voltage-gated ion channels, on membrane potential variation. Membrane
      patches of Xenopus laevis oocytes microinjected with exogenous KAT1 cRNA,
      deposited by a stripping method at the surface of a derivatized gold film in
      inside-out configuration, have been imaged by SFM in an electrochemical cell. A
      potentiostat was used to maintain a desired potential drop across the membrane.
      Performing imaging at potential values corresponding to open (-120 mV) and closed
      (+20 mV) states for KAT1, morphological differences in localized sample zones
      were observed. Particularly, cross-shaped features involving a significant
      membrane portion appear around putative channel locations. The reported approach
      constitutes the first demonstration of an SPM-based experimental technique
      suitable to investigate the rearrangements occurring to the plasma membrane
      containing voltage-gated channels on transmembrane potential variation.

PMID- 18058827
TI  - CoagMDB: a database analysis of missense mutations within four conserved domains
      in five vitamin K-dependent coagulation serine proteases using a text-mining
      tool.
AB  - Central repositories of mutations that combine structural, sequence, and
      phenotypic information in related proteins will facilitate the diagnosis and
      molecular understanding of diseases associated with them. Coagulation involves
      the sequential activation of serine proteases and regulators in order to yield
      stable blood clots while maintaining hemostasis. Five coagulation serine
      proteases-factor VII (F7), factor IX (F9), factor X (F10), protein C (PROC), and
      thrombin (F2)-exhibit high sequence similarities and all require vitamin K. All
      five of these were incorporated into an interactive database of mutations named
      CoagMDB (http://www.coagMDB.org; last accessed: 9 August 2007). The large number
      of mutations involved (especially for factor IX) and the increasing problem of
      out-of-date databases required the development of new database management tools.
      A text mining tool automatically scans full-length references to identify and
      extract mutations. High recall rates between 96 and 99% and precision rates of 87
      to 93% were achieved. Text mining significantly reduces the time and expertise
      required to maintain the databases and offers a solution to the problem of locus
      specific database management and upkeep. A total of 875 mutations were extracted
      from 1,279 literature sources. Of these, 116 correspond to Gla domains, 86 to the
      N-terminal EGF domain, 73 to the C-terminal EGF domain, and 477 to the serine
      protease domain. The combination of text mining and consensus domain structures
      enables mutations to be correlated with experimentally-measurable phenotypes
      based on either low protein levels (Type I) or reduced functional activities
      (Type II), respectively. A tendency for the conservation of phenotype with
      structural location was identified.

PMID- 18058828
TI  - Influence of comorbidity and cognitive status on instrumental activities of daily
      living in amnestic mild cognitive impairment: results from the ReGAl project.
AB  - OBJECTIVES: To investigate whether amnestic mild cognitive impairment (aMCI) is
      characterised by restriction in instrumental activities of daily living (IADL).
      Further, to examine the role of comorbidity and cognitive performance on IADL
      changes in aMCI subjects. METHODS: The study included 132 subjects with aMCI and
      249 subjects with no cognitive impairment (NCI), consecutively enrolled as
      outpatients in a multicentric Italian clinical-based study, the ReGAl Project.
      All subjects underwent a comprehensive evaluation including clinical examination,
      laboratory screening, neuroimaging and cognitive and behavioral assessments.
      Functional status was evaluated by the Lawton's Instrumental Activities of Daily
      Living (IADL) scale. Comorbidity was evaluated by the Cumulative Illness Rating
      Scale (CIRS). Cognitive evaluation included tests assessing episodic memory,
      language, attention/executive functioning and praxis, as well as the the Mini
      Mental State Examination (MMSE) as a measure of global cognition. RESULTS:
      Subjects with aMCI had higher IADL changes than NCI. Among IADL items, aMCI
      subjects showed a significant impairment in shopping, taking drugs, and handling
      economy; however also NCI had minor IADL changes regarding cooking, washing and
      cleaning. IADL restriction in aMCI subjects was significantly associated with
      cognitive performance, mainly related to executive functioning, but not with
      comorbidity. On the contrary, in NCI sensory impairment accounts for slight IADL
      changes. CONCLUSION: In aMCI subjects a mild degree of cognitive deterioration
      has a stronger impact on IADL than somatic comorbidity. Current diagnostic
      criteria for MCI should include a mild impairment in IADL.

PMID- 18058829
TI  - A likelihood-based method for real-time estimation of the serial interval and
      reproductive number of an epidemic.
AB  - We present a method for the simultaneous estimation of the basic reproductive
      number, R(0), and the serial interval for infectious disease epidemics, using
      readily available surveillance data. These estimates can be obtained in real time
      to inform an appropriate public health response to the outbreak. We show how this
      methodology, in its most simple case, is related to a branching process and
      describe similarities between the two that allow us to draw parallels which
      enable us to understand some of the theoretical properties of our estimators. We
      provide simulation results that illustrate the efficacy of the method for
      estimating R(0) and the serial interval in real time. Finally, we implement our
      proposed method with data from three infectious disease outbreaks.

PMID- 18058830
TI  - Medication errors in older people with mental health problems: a review.
AB  - OBJECTIVE: To review and summarise published data on medication errors in older
      people with mental health problems. METHODS: A systematic review was conducted to
      identify studies that investigated medication errors in older people with mental
      health problems. MEDLINE, EMBASE, PHARMLINE, COCHRANE COLLABORATION and PsycINFO
      were searched electronically. Any studies identified were scrutinized for further
      references. The title, abstract or full text was systematically reviewed for
      relevance. RESULTS: Data were extracted from eight studies. In total, information
      about 728 errors (459 administration, 248 prescribing, 7 dispensing, 12
      transcribing, 2 unclassified) was available. The dataset related almost
      exclusively to inpatients, frequently involved non-psychotropics, and the
      majority of the errors were not serious. CONCLUSIONS: Due to methodology issues
      it was impossible to calculate overall error rates. Future research should
      concentrate on serious errors within community settings, and clarify potential
      risk factors.

PMID- 18058831
TI  - APOE genotype predicts depression in women with Alzheimer's disease: a
      retrospective study.
AB  - OBJECTIVE: The association between the APOE epsilon4 allele and depression was
      investigated in a retrospective study of 323 AD patients. METHODS: Patients were
      divided into demographically comparable groups based on the presence or absence
      of depression. RESULTS: Results showed that the frequency of APOE epsilon4 allele
      was significantly higher in the depressed vs non-depressed AD patients (72% and
      58%, respectively), and an interaction revealed that women possessing the APOE
      epsilon4 allele were almost four times more likely to be depressed than those
      without the epsilon4 allele. CONCLUSION: Results are consistent with recent
      suggestions that the APOE epsilon4 genotype may be over-represented among
      depressed women with AD and highlight the need for additional research
      investigating the links between APOE genotype, mood, and gender.

PMID- 18058833
TI  - An exploration of spousal separation and adaptation to long-term disability: six
      elderly couples engaged in a horticultural programme.
AB  - The main objective of the present study was to explore the impact of separation
      on couples where one spouse lives in a skilled nursing facility and the other
      spouse lives alone in the community. Six couples participated in a 10-week
      gardening group. Semi-structured interviews were conducted at the beginning of
      the study and observations were made and discussions engaged through the 10-week
      horticultural programme. Thematic analysis of interviews and discussions revealed
      reduced social participation of community-dwelling spouses in an effort to
      maintain their marital role. In one or more cases the non-institutionalized
      spouse adapted to separation by developing social roles and relationships within
      the skilled nursing facility and continuing as a caregiver to their spouse.
      Occupational therapists are encouraged to include spouses in programmes to
      nurture healthy spousal roles. Further research is needed to explore how elderly
      couples may support each other through purposeful occupation while one spouse is
      in a long-term care facility.

PMID- 18058834
TI  - Characteristics associated with benzodiazepine usage in elderly outpatients in
      Taiwan.
AB  - OBJECTIVE: To investigate benzodiazepine usage and the characteristics associated
      with usage among elderly outpatients in Taiwan. METHODS: This was an
      observational study of subjects who were enrolled in the National Health
      Insurance program and aged at least 65 in 2002. They were grouped according to
      treatment period and mean dosage. An ordered logit regression model was used to
      evaluate associations of characteristics with benzodiazepine usage. RESULTS: Of
      the 4,267 elderly people included, 1,826 had received at least one prescription
      for benzodiazepines. The 1-year prevalence of benzodiazepine usage by elderly
      outpatients was approximately 43%. Characteristics associated with receiving
      benzodiazepine therapy included female gender, displaying comorbid insomnia,
      anxiety, depression, other mental diseases, cardiovascular disease, cancer,
      chronic obstructive pulmonary disease, arthritis, and previous use of
      benzodiazepines. Individuals older than 75 years, with comorbid insomnia,
      anxiety, depression, other mental diseases, cardiovascular disease, cancer, being
      in previous receipt of benzodiazepines, or high prescription-overlap ratio were
      more likely to receive longer treatment. Individuals with insomnia, anxiety,
      depression, and previous use of higher cumulative dosage of benzodiazepine were
      more likely to receive higher-dosage therapy. CONCLUSIONS: Mental disorders and
      previous exposure to higher cumulative dosages of benzodiazepines are associated
      with an increased likelihood of receiving benzodiazepine therapy, longer
      treatment, and a higher mean dosage. Older individuals, less likely to receive
      higher dosage benzodiazepine therapy, are more likely to receive more prolonged
      therapy. Women are more likely to receive benzodiazepine therapy, but both men
      and women have comparable benzodiazepine usage patterns.

PMID- 18058832
TI  - A double blind, placebo-controlled pilot study of galantamine augmentation of
      antidepressant treatment in older adults with major depression.
AB  - OBJECTIVE: Depression in older adults is often associated with cognitive
      abnormalities and may predict later development of a primary cognitive disorder.
      This double-blind, randomized, placebo-controlled pilot study was designed to
      assess the safety and efficacy of galantamine augmentation of antidepressant
      treatment for depressive and cognitive symptoms in older adults with major
      depression. METHODS: Thirty-eight, non-demented older adults (age >50) with major
      depression were randomized to receive galantamine or placebo augmentation of
      standard antidepressant pharmacotherapy (venlafaxine XR or citalopram). Mood and
      cognitive status were monitored for 24 weeks using the 24-item Hamilton Rating
      Scale for Depression and the Repeatable Battery for the Assessment of
      Neuropsychological Status. RESULTS: Both groups showed significant improvements
      in mood and cognition over 24 weeks, but no significant difference was found in
      change over time between groups. An exploratory post-hoc analysis suggested that
      patients randomized to galantamine had lower depression scores compared to
      patients in the placebo group after 2 weeks of treatment. Dropout was high with
      more subjects randomized to antidepressant plus galantamine withdrawing early
      from the study. CONCLUSIONS: This pilot study failed to demonstrate a benefit for
      galantamine augmentation of antidepressant medication in the treatment of
      depression in older adults. Future studies should explore strategies for reducing
      dropout in such longitudinal trials and more carefully assess time to response
      with cholinesterase inhibitor augmentation.

PMID- 18058835
TI  - Incidence of cardiovascular events in breast cancer patients receiving
      chemotherapy in clinical practice.
AB  - PURPOSE: To assess the incidence of cardiovascular events among breast cancer
      patients after chemotherapy. METHODS: Women > or =18 years with a breast tumour
      who received chemotherapy in 1992-2003 were selected from the PHARMO RLS.
      Chemotherapy with anthracyclines, a combination of anthracyclines and taxanes or
      second line treatment with trastuzumab was classified as cardiotoxic.
      Cardiovascular events were determined based on drug use and hospital admissions.
      Incidence rates of cardiovascular events and hazard ratios (HR) for the
      cardiotoxic versus non-cardiotoxic chemotherapy group were assessed during the
      first year and total follow-up. RESULTS: Of 648 patients with breast cancer
      included in the study cohort, 353 (54%) received cardiotoxic chemotherapy. At
      baseline, patients who received cardiotoxic chemotherapy compared with patients
      receiving non-cardiotoxic chemotherapy, received less anticoagulants/haemostatics
      (5 vs. 11%; p = 0.012) and had been less often hospitalised for cardiovascular
      disease (1 vs. 5%; p = 0.007) 2 years before the cohort entry date. After 1-year
      follow-up, the incidence rate of cardiovascular events was 69/1000 person years
      (py) for patients with cardiotoxic chemotherapy and 98/1000 py for patients with
      non-cardiotoxic chemotherapy, which did not differ significantly (HR 0.74 95%
      confidence interval (CI): 0.39, 1.41). After total follow-up, this was 81/1000 py
      for patients with cardiotoxic and 92/1000 py for patients with non-cardiotoxic
      chemotherapy (HR 0.81, 95%CI: 0.54, 1.20). CONCLUSIONS: This study showed similar
      cardiovascular incidence rates during follow-up for breast cancer patients
      treated with cardiotoxic and non-cardiotoxic chemotherapy. Specialists seemed to
      take pre-existing cardiovascular diseases into account when treating the breast
      cancer patient.

PMID- 18058838
TI  - Improvement in behavioural symptoms in patients with moderate to severe
      Alzheimer's disease by memantine: a pooled data analysis.
AB  - INTRODUCTION: Behavioural disturbances are a common and distressing aspect of
      Alzheimer's disease (AD). This pooled analysis evaluated the specific benefits of
      memantine on behavioural disturbances in patients with moderate to severe AD.
      METHODS: Data were pooled from six 24/28-week, randomised, placebo-controlled,
      double-blind studies. Of the 2,311 patients included in these studies, 1,826
      patients with moderate to severe AD (MMSE <20) were included in this analysis,
      corresponding to the extended indication for memantine in Europe. In this
      subgroup, 959 patients received memantine 20 mg/day and 867 received placebo.
      Behavioural symptoms were rated using the Neuropsychiatric Inventory (NPI) total
      and single-item scores at weeks 12 and 24/28. RESULTS: At weeks 12 and 24/28, ITT
      analysis demonstrated that memantine treatment produced statistically significant
      benefits over placebo treatment in NPI total score (p=0.001 and p=0.008), and in
      NPI single items: delusions (p=0.007 week 12, p=0.001 week 24/28), hallucinations
      (p=0.037 week 12), agitation/aggression (p=0.001 week 12, p=0.001 week 24/28),
      and irritability/lability (p=0.005 week 24/28), LOCF population. Analysis of the
      patients without symptoms at baseline indicated reduced emergence of
      agitation/aggression (p=0.002), delusions (p=0.047), and disinhibition (p=0.011),
      at week 12, and of agitation/aggression (p=0.002), irritability/lability
      (p=0.004), and night-time behaviour (p=0.050) at week 24/28 in those receiving
      memantine. OC analyses yielded similar results. CONCLUSIONS: The data suggest
      that memantine is effective in treating and preventing the behavioural symptoms
      of moderate to severe AD. Specific persistent benefits were observed on the
      symptoms of delusions and agitation/aggression, which are known to be associated
      with rapid disease progression, increased caregiver burden, early
      institutionalisation, and increased costs of care.

PMID- 18058839
TI  - European commission consultation on pharmacovigilance.

PMID- 18058842
TI  - Predictive value of angiogenic factors and uterine artery Doppler for early-
      versus late-onset pre-eclampsia and intrauterine growth restriction.
AB  - OBJECTIVES: To investigate potential differences in the prediction of early- vs.
      late-onset pre-eclampsia and/or intrauterine growth restriction (PE/IUGR) by
      second-trimester uterine artery Doppler examination, and measurement of maternal
      serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1
      (sFlt1). METHODS: Uterine artery mean pulsatility index (PI) and maternal serum
      PlGF and sFlt1 levels were measured at 24 weeks of gestation in 76 healthy
      pregnant women and 38 cases of PE/IUGR, of which 19 were defined as early onset
      (< 32 weeks). RESULTS: For a specificity of 95%, the sensitivities of uterine
      artery mean PI, PlGF and sFlt1 for early-onset PE/IUGR were 47.4%, 84.4% and
      36.8%, respectively. When combining uterine artery Doppler with PlGF, the
      sensitivity for identifying early-onset PE/IUGR was 89.5% with a specificity of
      95%. Conversely, the sensitivity for late-onset PE/IUGR was below 11% for all
      parameters analyzed. CONCLUSIONS: Angiogenic factors and uterine artery Doppler
      evaluation may be useful second-trimester screening tests for early-onset, but
      not late-onset, PE/IUGR.

PMID- 18058843
TI  - Prenatal diagnosis of dumbbell neuroblastoma.
AB  - A neuroblastoma that develops in the sympathetic nodes can infiltrate the
      intervertebral foramina and invade the spinal canal, leading to spinal cord and
      nerve root compression and neurological impairment. Dumbbell neuroblastomas are
      now considered to be unresectable tumors and preoperative chemotherapy is
      recommended. We report the prenatal diagnosis of a dumbbell neuroblastoma
      successfully managed through premature delivery followed by immediate
      chemotherapy. We suggest that delivering prematurely in such cases is only of
      benefit if chemotherapy can be administered under favorable conditions.
      Chemotherapy should proceed immediately after delivery in order to reduce the
      size of the tumoral mass and its effects on the spine.

PMID- 18058844
TI  - Free fatty acids as mediators of adaptive compensatory responses to insulin
      resistance in dexamethasone-treated rats.
AB  - BACKGROUND: Chronic low-dose dexamethasone (DEX) treatment in rats is associated
      to insulin resistance with compensatory hyperinsulinaemia and reduction in food
      intake. We tested the hypothesis that the elevation in circulating free fatty
      acids (FFAs) induced by DEX is the common mediator of both insulin resistance and
      insulin hyperproduction. METHODS: For this purpose, an anti-lipolytic agent was
      administered during DEX treatment to lower lipacidaemia for several hours prior
      to glucose and insulin tolerance tests. Leptin expression in adipose tissue (by
      Northern blot) and plasma leptin levels (by radioimmunoassay) were also
      investigated to verify whether a rise in circulating leptin could be responsible
      for the anorectic effect of DEX. RESULTS: Our data show that a transient
      pharmacological reduction of elevated plasma FFA levels abates the post-loading
      hyperinsulinaemia and counteracts the insulin resistance induced by DEX,
      supporting the hypothesis that the chronic elevation in FFAs is the common
      mediator of DEX-induced changes. Despite enhanced leptin expression in white
      adipose tissue, DEX-treated rats show no significant increase in plasma leptin
      levels. This suggests that the anorectic effect of DEX should be mediated, at
      least partially, by other factors, possibly related to the influence of
      concomitantly elevated plasma FFA and insulin levels on the hypothalamic centers
      regulating feeding. CONCLUSIONS: Our results sustain the idea that a prolonged
      increase in plasma FFA levels plays an important role in the adaptive regulation
      of glucose and energy homeostasis, not only by potentiating insulin secretion but
      also by providing a signal of 'nutrient abundance' capable of restraining food
      intake.

PMID- 18058845
TI  - Selection of important variables and determination of functional form for
      continuous predictors in multivariable model building.
AB  - In developing regression models, data analysts are often faced with many
      predictor variables that may influence an outcome variable. After more than half
      a century of research, the 'best' way of selecting a multivariable model is still
      unresolved. It is generally agreed that subject matter knowledge, when available,
      should guide model building. However, such knowledge is often limited, and data
      dependent model building is required. We limit the scope of the modelling
      exercise to selecting important predictors and choosing interpretable and
      transportable functions for continuous predictors. Assuming linear functions,
      stepwise selection and all-subset strategies are discussed; the key tuning
      parameters are the nominal P-value for testing a variable for inclusion and the
      penalty for model complexity, respectively. We argue that stepwise procedures
      perform better than a literature-based assessment would suggest. Concerning
      selection of functional form for continuous predictors, the principal competitors
      are fractional polynomial functions and various types of spline techniques. We
      note that a rigorous selection strategy known as multivariable fractional
      polynomials (MFP) has been developed. No spline-based procedure for
      simultaneously selecting variables and functional forms has found wide
      acceptance. Results of FP and spline modelling are compared in two data sets. It
      is shown that spline modelling, while extremely flexible, can generate fitted
      curves with uninterpretable 'wiggles', particularly when automatic methods for
      choosing the smoothness are employed. We give general recommendations to
      practitioners for carrying out variable and function selection. While
      acknowledging that further research is needed, we argue why MFP is our preferred
      approach for multivariable model building with continuous covariates.

PMID- 18058847
TI  - Cost-effectiveness analysis in colorectal cancer using a semi-Markov model.
AB  - Cost and effectiveness are usually modeled according to one studied event or one
      health state with parametric or non-parametric methods. In this paper, we propose
      an original method for assessing total costs while incorporating the dynamics of
      change in the health status of patients. A semi-Markov model in which the
      distributions of sojourn times are explicitly defined is developed. The hazard
      function of sojourn times is modeled by Weibull distributions specific to each
      transition. A vector of covariates is incorporated into the hazard function of
      each transition. From a regression model for costs, a cumulative cost function is
      derived. An estimation of the mean cost per patient in each state defined in the
      semi-Markov model could thus be made, and this enables us to identify the
      determinants of direct costs. The results of incremental net benefit (INB) are
      assessed using the bootstrap method. A cost-effectiveness analysis is performed
      in order to compare two strategies of follow-up in the colorectal cancer study.
      Two hundred and forty patients were enrolled in this study. Three health states
      are defined for patients with curative resection of colorectal cancer: alive
      without relapse, alive with relapse, and dead. The mean survival is 4.35 and 4.12
      years, respectively, in the standard and moderate follow-up groups. We show that
      mean cost differs significantly by follow-up strategy and Dukes stage. Finally,
      the INB is assessed and this indicates that neither of the strategies compared
      was more cost-effective than the other.

PMID- 18058848
TI  - Statistical analysis of donation--transfusion data with complex correlation.
AB  - Blood-borne transmission of disease is estimated from linked data records from
      blood donors and transfusion recipients. However, such data are characterized by
      complex correlation due to donors typically contributing many donations and
      recipients being transfused with multiple units of blood product. In this paper,
      we present a method for analysing such data, by using a modification of a nested
      case-control design. For recipients who develop the disease of interest (cases)
      and their matched controls, all donors who contributed blood to these individuals
      define clusters or 'families' of related individuals. Using a Cox regression
      model for the hazard of the individuals within clusters of donors, we estimate
      the risk of transmission, and a bootstrap step provides valid standard errors
      provided the clusters are independent. As an illustration, we apply the method to
      the analysis of a large database of Swedish donor and recipient records linked to
      the population cancer register. We investigate whether there is an increased risk
      of cancer in recipients transfused with blood from donors who develop cancer
      after donating. Our method provides a powerful alternative to the small 'look
      back' studies typical of transfusion medicine and can make an important
      contribution to haemovigilance efforts.

PMID- 18058849
TI  - Factors associated with treatment nonadherence among US bipolar disorder
      patients.
AB  - OBJECTIVE: Since sustained treatment-adherence is often problematic and may limit
      clinical outcomes among bipolar disorder (BPD) patients, we sought risk factors
      to guide clinical prediction of nonadherence. METHODS: Data were from a 2005 US
      national sample providing questionnaire responses by 131 randomly selected
      prescribing psychiatrists and their adult BPD patients. We contrasted demographic
      and clinical factors in treatment-adherent versus nonadherent patients (strictly
      defined as missing > or =1 dose within 10 days) in univariate analyses followed
      by multivariate logistic-regression modeling. RESULTS: Of 429 DSM-IV BPD patients
      (79% type-I; 62% women; 17% minorities), 34% reported missing > or = 1 dose of
      psychotropic medication within 10 days, 20% missed entire daily doses at least
      once, and only 2.5% missed all doses for 10 days. However, their prescribing
      psychiatrists considered only 6% as treatment-nonadherent. Factors significantly
      associated with nonadherence in multivariate modeling ranked: alcohol-dependence
      > youth > greater affective morbidity > various side effects > or = comorbid
      obsessive-compulsive disorder > or = recovering from mania-hypomania. Unrelated
      were sex, diagnostic subtype, and other comorbidities. Since most patients
      received > or = 2 psychotropics, potential relationships between treatment
      complexity and adherence were obscured. CONCLUSIONS: Prevalent treatment
      nonadherence among American BPD patients, and striking underestimation of the
      problem by prescribing clinicians may encourage increasingly complex treatment
      regimens of untested value, but added expense, risk of adverse effects, and
      uncertain impact on treatment-adherence itself.

PMID- 18058850
TI  - Assessing surrogacy from the joint modelling of multivariate longitudinal data
      and survival: application to clinical trial data on chronic lymphocytic
      leukaemia.
AB  - In clinical research, we are often interested in assessing how a biomarker
      changes with time, and whether it could be used as a surrogate marker when
      evaluating the efficacy of a new drug. However, when the longitudinal marker is
      correlated with survival, linear mixed models for longitudinal data may be
      inappropriate. By contrast, it may be possible to recover information from the so
      called informative censoring by modelling both the longitudinal information and
      the survival process. The objective of this work is to jointly model longitudinal
      and survival data to assess surrogacy. Two competitive modelling strategies were
      used, either a multistate model summarizing the course of longitudinal data and
      occurrence of disease progression or death, or a joint longitudinal-survival
      model. We present both analyses based on a case study from two randomized
      clinical trials that enrolled patients with stage A chronic lymphocytic leukaemia
      (CLL) in order to obtain further insights into these different approaches.

PMID- 18058851
TI  - Stratification for the propensity score compared with linear regression
      techniques to assess the effect of treatment or exposure.
AB  - Stratifying and matching by the propensity score are increasingly popular
      approaches to deal with confounding in medical studies investigating effects of a
      treatment or exposure. A more traditional alternative technique is the direct
      adjustment for confounding in regression models. This paper discusses fundamental
      differences between the two approaches, with a focus on linear regression and
      propensity score stratification, and identifies points to be considered for an
      adequate comparison. The treatment estimators are examined for unbiasedness and
      efficiency. This is illustrated in an application to real data and supplemented
      by an investigation on properties of the estimators for a range of underlying
      linear models. We demonstrate that in specific circumstances the propensity score
      estimator is identical to the effect estimated from a full linear model, even if
      it is built on coarser covariate strata than the linear model. As a consequence
      the coarsening property of the propensity score-adjustment for a one-dimensional
      confounder instead of a high-dimensional covariate-may be viewed as a way to
      implement a pre-specified, richly parametrized linear model. We conclude that the
      propensity score estimator inherits the potential for overfitting and that care
      should be taken to restrict covariates to those relevant for outcome.

PMID- 18058852
TI  - High-dose escitalopram in the treatment of binge-eating disorder with obesity: a
      placebo-controlled monotherapy trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of
      high-dose escitalopram in the treatment of binge-eating disorder (BED) associated
      with obesity. METHOD: Forty-four outpatients with BED by DSM-IV criteria and
      obesity were randomized to receive either escitalopram (N = 21) or placebo (N =
      23) in a 12-week, double-blind, flexible dose (10-30 mg/day) study. RESULTS: In
      the primary analysis, escitalopram (mean dose 26.5 mg/day) and placebo had
      similar rates of reduction of binge episodes, binge days and obsessive-compulsive
      symptoms of BED. However, escitalopram was associated with statistically
      significant reductions in weight, body mass index (BMI), and global severity of
      illness scores. In a secondary analysis, escitalopram was associated with
      statistically significant reductions in frequency of binge episodes and binge
      days, weight, BMI and severity of illness, but not in obsessive-compulsive
      symptoms of BED. No changes in metabolic variables, including measures of ghrelin
      and leptin, were observed. High-dose escitalopram was well tolerated. CONCLUSION:
      High-dose escitalopram was not efficacious in reducing obsessive-compulsive
      symptoms of BED, but was efficacious in reducing weight and global severity of
      illness. No definitive conclusions about its efficacy in reducing binge-eating
      frequency could be drawn due to limitations related to statistical power.

PMID- 18058854
TI  - Robustness of a parametric model for informatively censored bivariate
      longitudinal data under misspecification of its distributional assumptions: A
      simulation study.
AB  - Repeated measurements of surrogate markers are frequently used to track disease
      progression, but these series are often prematurely terminated due to disease
      progression or death. Analysing such data through standard likelihood-based
      approaches can yield severely biased estimates if the censoring mechanism is non
      ignorable. Motivated by this problem, we have proposed the bivariate joint
      multivariate random effects (JMRE) model, which has shown that when correctly
      specified it performs well in terms of bias reduction and precision. The
      bivariate JMRE model is fully parametric and belongs to the class of shared
      parameters joint models where a survival model for the dropouts and a mixed model
      for the markers' evolution are linked through a multivariate normal distribution
      of random effects. As in every parametric model, robustness under violations of
      its distributional assumptions is of great importance. In this study we generated
      500 simulated data sets assuming that random effects jointly follow a heavy
      tailed distribution, two skewed distributions or a mixture of two normal
      distributions. Moreover, we generated data where level-1 errors or residuals in
      the survival part of the model follow a skewed distribution. Further sensitivity
      analysis on the effects of reduced sample size, increased level-1 variances and
      altered fixed effects values was also performed. We found that fixed effects
      estimates are almost unaffected, but their standard errors (SEs) may be
      underestimated especially under heavily skewed distributions. The proposed model
      seems robust enough, but its performance on smaller data sets or under more
      extreme departures of its assumptions needs further investigation.

PMID- 18058856
TI  - Dietary intake and risk evaluation of polybrominated diphenyl ethers in The
      Netherlands.
AB  - The current study aims at estimating the dietary intake of PBDEs in the
      Netherlands and evaluating the resultant risk. Dietary intake was estimated using
      results of PBDE analyses in Dutch food products from 2003/2004 and consumption
      data of the third Dutch National Food Consumption Survey (1997/1998). Assuming
      that non-detects represent levels of half the detection limit, the median long
      term intake of the Dutch population of the sum of five major PBDEs (namely PBDEs
      47, 99, 100, 153+154) is 0.79 ng/kg body weight bw/day (P97.5: 1.62 ng/kg
      bw/day). When non-detects are considered as zeros the values are 0.53 (median)
      and 1.34 (P97.5) ng/kg bw/day. Environmental concentrations of PBDEs in Europe
      are expected to decline in the near future because of the ban on penta- and
      octaBDE technical products. However, it will take at least a decade before this
      will result in lower PBDE concentrations in food products. Hence, a regular
      monitoring program for PBDEs is recommended. A risk evaluation at the most
      sensitive endpoints of BDE 99 carried out in this paper indicates that, although
      the long-term exposure to BDE 99 is well below the human exposure threshold level
      for neurodevelopmental toxicity, it may be close to that for reproductive
      toxicity.

PMID- 18058857
TI  - Human papillomavirus, cervical carcinogenesis and chemoprevention with Indole
      derivates - a review of pathomechanisms.
AB  - Cervical cancer is the second most common female cancer worldwide with high risk
      Human Papillomavirus (HPV) infection playing an essential aetiological role.
      Oestrogen interacts with HPV at a cellular level causing cell growth and
      inhibition of apoptosis. Indole derivatives, formed during digestion of
      cruciferous vegetables, have been shown to have chemopreventative properties
      inhibiting HPV transcription and influencing oestrogen metabolism. This review
      describes the interactions between HPV, oestrogen and indole derivatives. Further
      clinical research is required to evaluate the chemopreventative properties of
      these agents.

PMID- 18058858
TI  - Simultaneous determination of antiepileptic drugs and their two active
      metabolites by HPLC.
AB  - An HPLC procedure for the determination of lamotrigine (LAM) simultaneously with
      other antiepileptic drugs, primidone (PD), phenobarbital (PB), phenytoin (DPH),
      carbamazepine (CMZ), and two active metabolites 2-phenyl-2-ethyl-malonamide
      (PEMA) and 10,11-dihydro-10,11-epoxycarbamazepine (EPO) was developed and
      validated. The method involves an ordinary RP system and a liquid-liquid
      extraction. The mobile phase consisting of water/ACN/methanol/triethylamine in
      the ratio 72:23:5:0.1 with pH 7.0 was selected as the best one after the assays
      testing both pH and triethylamine contents. UV detection was carried out at a
      wavelength of 220 nm and the whole analysis took 15 min. The method was linear in
      the range of 0.5-25 mg/L for PEMA and LAM; 1.25-25 mg/L for PD and CMZ; 0.625
      12.5 mg/L for EPO; 1.5-60 mg/L for PB; and 1.25-50 mg/L for DPH, respectively.
      Within-day CV% and between-day CV% were within 10%. The developed HPLC method can
      be used for routine therapeutic drug monitoring both in children and adults.

PMID- 18058859
TI  - Capillary electrophoresis evidence of the stereoselective ketoreduction of
      mebendazole and aminomebendazole in echinococcosis patients.
AB  - An assay for the simultaneous determination of the enantiomers of
      hydroxymebendazole (OH-MBZ) and hydroxyaminomebendazole (OH-AMBZ) together with
      aminomebendazole (AMBZ) in human plasma is described for the first time. It is
      based upon liquid-liquid extraction at alkaline pH from 0.5 mL plasma followed by
      analysis of the reconstituted extract by CE with reversed polarity in the
      presence of a 50 mM, pH 4.2 acetate buffer containing 15 mg/mL sulfated beta-CD
      as chiral selector. For all compounds, detection limits are between 0.01 and 0.04
      microg/mL, and intraday and interday precisions evaluated from peak area ratios
      are <6.9 and <8.5%, respectively. Analysis of 39 samples of echinoccocosis
      patients undergoing pharmacotherapy with mebendazole (MBZ) revealed that the
      ketoreduction of MBZ and AMBZ is highly stereoselective. One enantiomer of each
      metabolite (firstly detected peak in both cases) could only be detected. The CE
      data revealed that OH-MBZ (mean: 0.715 microg/mL) is the major metabolite
      followed by AMBZ (mean: 0.165 microg/mL) and OH-AMBZ (mean: 0.055 microg/mL)
      whereas the MBZ plasma levels (mean: 0.096 microg/mL, levels determined by HPLC)
      were between those of AMBZ and OH-AMBZ.

PMID- 18058860
TI  - Rapid and sensitive determination of acrylamide in drinking water by planar
      chromatography and fluorescence detection after derivatization with dansulfinic
      acid.
AB  - On the basis of a novel derivatization, a new planar chromatographic method has
      been developed for the determination of acrylamide (AA) in drinking water at the
      ultra-trace level. After SPE, the water extracts were oversprayed on a high
      performance thin-layer chromatography (HPTLC) silica gel plate with the
      derivatization agent dansulfinic acid and derivatized in situ. Chromatography was
      performed with ethyl acetate and the fluorescent product was quantified at
      366/>400 nm. Verification was based on HPTLC-ESI/MS, HPTLC-direct analysis in
      real-time (DART)-TOF/MS and NMR. The routine HPTLC-fluorescence detection (FLD)
      method was validated for spiked drinking water. The regression analysis was
      linear (r >0.9918) in the range of 0.1-0.4 microg/L. LOD was calculated to be
      0.025 microg/L and experimentally proved for spiked samples at levels down to
      0.05 microg/L (S/N = 6) which was suited for monitoring the EU limit value of 0.1
      microg/L in drinking water (0.5 microg/L demanded by World Health Organization
      (WHO)/US Environmental Protection Agency (EPA)). Within-run precision and the
      mean between-run precision (RSD, n = 3, three concentration levels each) were
      evaluated to be 4.8 and 11.0%, respectively. The mean recovery (0.1, 0.2, and 0.3
      microg/L) was 96% corrected by the internal standard. The method, in comparison
      with HPLC-MS/MS showed comparable results and demonstrated the accuracy of the
      method.

PMID- 18058861
TI  - Molecular homochirality and the parity-violating energy difference. A critique
      with new proposals.
AB  - Previous proposals for the origin of molecular homochirality, based on the effect
      of the weak neutral current (WNC) on enantiomers, and the amplification of the
      resultant parity-violating energy difference (PVED), are possibly flawed. The
      additive amplification of PVED in crystals and polymers ("Yamagata hypothesis")
      cannot lead to detectable levels of optical activity, the original theory
      apparently overestimating PVED by a factor equal to Avogadro's number. An
      alternative theory based on the irreversible and spontaneous evolution of a
      dynamically fluctuating system is apparently impractical. However, the nonlinear
      amplification of PVED via autocatalytic polymerization may be possible as
      indicated by a simplified physico-chemical approach. This may also occur during
      crystallization and melting, and form the basis of the second order asymmetric
      transformation. (Thus, reported differences in the melting points of enantiomers
      in several cases may well be real). Also, the preponderance of racemic compounds
      over conglomerates may be based on the destabilization of the conglomerate by the
      action of the WNC on the crystalline lattice. The WNC may also be involved in the
      anomalous scattering of X-rays, which possibly arises from their circular
      polarization: the current theory would need to be revised accordingly.

PMID- 18058862
TI  - The resolution of five racemic alpha-lactams by HPLC.
AB  - The resolution of five racemic alpha-lactams (1a-d,g) using HPLC is reported.
      Five different Pirkle-type stationary phases were tested. The enantiomers of
      alpha-lactams containing the trityl group (1a-d) were separated (selectivity
      factors ranging from 1.08 to 1.20) using a mobile phase of hexane/2-propanol:98/2
      and a stationary phase consisting of the 3,5-dinitroaniline derivative of (S)
      valine with a urea linkage. Among the dialkyl-substituted alpha-lactams (1e-g),
      only 1,3-di-tert-butylaziridinone (1g) could be resolved, but only partially
      (selectivity factor = 1.07), with a mobile phase of hexane/1,2
      dichloroethane:95/5 and the stationary phase consisting of the 3,5-dinitrobenzoic
      acid derivative of (R)-1-naphthylglycine.

PMID- 18058863
TI  - Synthesis of chiral vicinal diols and analysis of them by capillary zone
      electrophoresis.
AB  - This paper describes an improved access to 1,4-bis (9-O-quininyl) phthalazine
      [(QN)(2)PHAL], a very useful chiral ligand for catalytic asymmetric
      dihydroxylation (AD), by using CaH(2) as acid-binding reagent in a high yield
      under mild conditions. The application of (QN)(2)PHAL to the AD reactions of
      eight olefins exhibited excellent enantioselectivity and activity with
      corresponding chiral vicinal diols. Furthermore, a capillary zone electrophoresis
      method was developed to separate the aforementioned chiral vicinal diols by using
      of neutral beta-cyclodextrin (beta-CD) as chiral selector and borate as running
      buffer. High resolution was achieved under the optimal conditions of beta-CD 2.2%
      (w/v), pH 10, 200 mM borate buffer at 15 kV, and 20 degrees C within 15 min. The
      relative standard deviations of the corrected peak areas and migration time were
      less than 3.9% and 1.3%, respectively. In addition, the developed method was
      successfully applied to the determination of the purity and the enantiomeric
      excesses value (%ee) of the AD reaction products.

PMID- 18058864
TI  - A DFT study of solvation effects on the tautomeric equilibrium and catalytic
      ylide generation of thiamin models.
AB  - Thiamin diphosphate (ThDP) is the biologically active form of vitamin B1 and an
      essential cofactor for a number of enzymes. The effect of solvent polarity on the
      tautomeric equilibria of ThDP using three model systems of the 4'-aminopyrimidine
      ring is studied by density functional theory calculations (B3LYP/6
      311+G(d,p)//B3LYP/6-31G(d)) in the gas phase and selected solvents (cyclohexane,
      ether, dichloroethane, and water). Solvation effects are investigated using three
      different schemes: implicit solvation by a continuum model, explicit solvation by
      inclusion of three water molecules mimicking the first solvation shell of the
      enzymatic environment, and by a mixed implicit/explicit solvation model. The 4'
      aminopyrimidine tautomer is more stable than the 1',4'-iminopyrimidine tautomer
      in all solvation schemes employed; however, the trend for the stabilities of the
      1',4'-iminopyrimidine tautomer in the solvents depends on the specific ThDP
      model. Formation of the catalytic important ylide for ThDP-dependent enzymes by
      deprotonation of ThDP(C2) is also investigated by localization of transition
      states for two possible pathways. Only the less stable tautomer, 1',4'
      iminopyrimidine ThDP, is able to form the catalytic active ylide. Generation of
      the ylide through a direct intramolecular proton transfer from ThDP(C2) to the
      ThDP(N4') nitrogen lone pair is favored by 6 kcal/mol in the gas phase, as
      compared to a water-mediated ylide generation. However, inclusion of a dielectric
      medium reduces this difference dramatically. Furthermore, inclusion of two water
      molecules to model the apoenzymatic environment lowers the activation energies of
      both direct and water-mediated ylide generation.

PMID- 18058865
TI  - The presence of halide salts influences the non-covalent interaction of MRI
      contrast agents and human serum albumin.
AB  - The rationale and objectives of the study were to evaluate the influence of the
      experimental conditions (buffer, salt, etc.) on the data characterizing the non
      covalent interaction between MRI contrast agents and human serum albumin and
      hence their in vivo relaxivity. The interaction of three gadolinium contrast
      agents (Gd-EOB-DTPA, Gd-BOPTA and MP-2269) with human serum albumin was assessed
      through the measurement of proton relaxation rate enhancement in various
      experimental conditions. The data show the negative effect of halide salts on the
      paramagnetic relaxation enhancement of the three contrast agents. The presence of
      halide salts can thus have a negative effect on the efficacy of MRI contrast
      agents interacting with HSA. In addition, careful attention must be paid to
      comparisons of the binding parameters of various contrast agents reported in
      different studies since the composition of the medium can greatly influence the
      non-covalent interaction.

PMID- 18058866
TI  - Reporter gene imaging using radiographic contrast from nonradioactive iodide
      sequestered by the sodium-iodide symporter.
AB  - The hypothesis that the human sodium-iodide symporter, NIS, can be used to detect
      NIS expression using standard radiological techniques was tested using adenoviral
      transduced NIS expression in human tumor xenografts grown in mice and in a naive
      dog prostate. Nonradioactive iodide was administered systemically to animals that
      1-3 days previously had received a local injection of a replication-competent
      adenovirus expressing NIS under the control of the CMV promoter. The distribution
      of radiopacity was assessed in mouse tumors using micro-CT and a clinical X-ray
      machine and in the prostate of an anesthetized dog using a clinical spiral CT.
      Iodide sequestration and NIS expression were measured using X-ray spectrochemical
      analysis and fluorescence microscopy, respectively. Radiographic contrast due to
      NIS gene expression that was observed indicates the technique has potential for
      use in preclinical rodent tumor studies but probably lacks sensitivity for human
      use.

PMID- 18058867
TI  - Alignment by the convective and vortex flow of achiral self-assembled fibers
      induces strong circular dichroism effects.

PMID- 18058868
TI  - Novel reactivity of side-on (disulfido)dicopper complexes supported by bi- and
      tridentate nitrogen donors: impact of axial coordination.

PMID- 18058869
TI  - Hole control in microporous polymers.

PMID- 18058870
TI  - High-pressure polymorphism as a step towards destabilization of LiBH4.

PMID- 18058871
TI  - Induction of optical activity in an oligothiophene synchronized with pH-sensitive
      folding of amylose.
AB  - Control of the helical sense in alpha-sexithiophene (6T) through pH-responsive
      wrapping with left-handed-helical amylose is demonstrated. A change in pH of the
      medium caused a significant conformational change in amylose as the host polymer,
      which resulted in either supramolecular complexation with 6T as the guest
      molecule to induce optical activity or decomplexation leading to loss of optical
      activity. Furthermore, we observed that chirality reversal in 6T does not require
      hosts of opposite helical chirality, but can be made possible simply by taking
      advantage of the pH sensitivity of the amylose folding, which is dependent on the
      pH history of the aqueous medium. In helical amylose, 6T assumes a clockwise
      twisted conformation when the pH is changed from acidic to neutral, but assumes
      an anticlockwise-twisted conformation when the aqueous solution is acidified from
      very basic conditions.

PMID- 18058872
TI  - A crown ether as template for microporous and nanostructured uranium compounds.

PMID- 18058873
TI  - Achiral nucleobase cytosine acts as an origin of homochirality of biomolecules in
      conjunction with asymmetric autocatalysis.

PMID- 18058874
TI  - Reductive coupling of acetonitrile by uranium and thorium hydride complexes to
      give cyanopentadienyl dianion (C6N3H7)2-.

PMID- 18058875
TI  - Chlorotonil A, a macrolide with a unique gem-dichloro-1,3-dione functionality
      from Sorangium cellulosum, So ce1525.

PMID- 18058876
TI  - DNA minicircles with gaps for versatile functionalization.

PMID- 18058877
TI  - Iron-catalyzed C-O cross-couplings of phenols with aryl iodides.

PMID- 18058878
TI  - Benzimidazole/amine-based compounds capable of ambipolar transport for
      application in single-layer blue-emitting OLEDs and as hosts for phosphorescent
      emitters.

PMID- 18058879
TI  - Efficient photoswitching of the nonlinear optical properties of dipolar
      photochromic zinc(II) complexes.

PMID- 18058880
TI  - Tetrazarsoles--a new class of binary arsenic-nitrogen heterocycles.

PMID- 18058881
TI  - Asymmetric synthesis and biological properties of uncialamycin and 26-epi
      uncialamycin.

PMID- 18058882
TI  - Amavadin and other vanadium complexes as remarkably efficient catalysts for one
      pot conversion of ethane to propionic and acetic acids.
AB  - Synthetic amavadin Ca[V{ON[CH(CH(3))COO](2)}(2)] and its models
      Ca[V{ON(CH(2)COO)(2)}(2)] and [VO{N(CH(2)CH(2)O)(3)}], in the presence of
      K(2)S(2)O(8) in trifluoroacetic acid (TFA), exhibit remarkable catalytic activity
      for the one-pot carboxylation of ethane to propionic and acetic acids with the
      former as the main product (overall yields up to 93 %, catalyst turnover numbers
      (TONs) up to 2.0 x 10(4)). The simpler V complexes [VO(CF(3)SO(3))(2)],
      [VO(acac)(2)] and VOSO(4) are less active. The effects of various factors,
      namely, C(2)H(6) and CO pressures, time, temperature, and amounts of catalyst,
      TFA and K(2)S(2)O(8), have been investigated, and this allowed optimisation of
      the process and control of selectivity. (13)C-labelling experiments indicated
      that the formation of acetic acid follows two pathways, the dominant one via
      oxidation of ethane with preservation of the C--C bond, and the other via rupture
      of this bond and carbonylation of the methyl group by CO; the C--C bond is
      retained in the formation of propionic acid upon carbonylation of ethane. The
      reactions proceed via both C- and O-centred radicals, as shown by experiments
      with radical traps. On the basis of detailed DFT calculations, plausible reaction
      mechanisms are discussed. The carboxylation of ethane in the presence of CO
      follows the sequential formation of C(2)H(5) (*), C(2)H(5)CO(*), C(2)H(5)COO(*)
      and C(2)H(5)COOH. The C(2)H(5)COO(*) radical is easily formed on reaction of
      C(2)H(5)CO(*) with a peroxo V catalyst via a V{eta(1)-OOC(O)C(2)H(5)}
      intermediate. In the absence of CO, carboxylation proceeds by reaction of
      C(2)H(5) (*) with TFA. For the oxidation of ethane to acetic acid, either with
      preservation or cleavage of the C-C bond, metal-assisted and purely organic
      pathways are also proposed and discussed.

PMID- 18058883
TI  - Tuning the charge distribution and photoswitchable properties of cobalt-dioxolene
      complexes by using molecular techniques.
AB  - A series of cobalt complexes [Co(Me(n)tpa)(diox)]PF(6)sol (diox=3,5-di-tert-butyl
      1,2-dioxolene; sol=ethanol, toluene; tpa=tris(2-pyridylmethyl)amine) were
      prepared by using tripod-like Me(n)tpa (n=0, 1, 2, 3), derived from tpa by
      successive introduction of methyl groups into the 6-position of the pyridine
      moieties, as an ancillary ligand. The steric hindrance induced by this
      substitution modulates the redox properties of the metal acceptor, thus
      determining the charge distribution of the metal-dioxolene moiety at room
      temperature. All of these complexes were characterised by using diffractometric
      studies, electronic spectroscopic analysis, and magnetic susceptibility
      measurements. In the solid state, the [Co(Me(n)tpa)(diox)](+) ions (n=0, 1) can
      be described as diamagnetic cobalt(III)-catecholato derivatives, whereas a
      cobalt(II)-semiquinonato description seems appropriate for the paramagnetic
      [Co(Me(3)tpa)(diox)](+) complex. The complex [Co(Me(2)tpa)(diox)]PF(6)C(2)H(5)OH
      undergoes entropy-driven valence tautomeric interconversion at room temperature.
      Optically induced valence tautomerism was observed by irradiation of
      [Co(Me(n)tpa)(diox)]PF(6) complexes (n=0, 1, 2) at cryogenic temperatures. The
      different relaxation kinetics of the photoinduced metastable phases are related
      to the respective free-energy changes of the interconversion, as estimated by
      cyclic voltammetric experiments at room temperature, and to the different lattice
      interactions, as supported by structural data. These results show the importance
      of molecular techniques for controlling the relaxation properties of photoinduced
      metastable species. At the same time, this behaviour strongly suggests that this
      paradigm exhibits intrinsic limits because of the less controllable factors that
      affect the process.

PMID- 18058884
TI  - Precursor approach to lanthanide dioxo monocarbodiimides Ln2O2CN2 (Ln=Y, Ho, Er,
      Yb) by insertion of CO2 into organometallic Ln-N compounds.
AB  - We present two organometallic precursor approaches leading to the hitherto
      unknown dioxo monocarbodiimides (Ln(2)O(2)CN(2)) of the late lanthanides Ho, Er,
      and Yb as well as yttrium. One involves insertion of CO(2), and the other one is
      a straightforward route using a molecular single-source precursor. To this end
      the reactivity of the activated amido lanthanide compound [(Cp(2)ErNH(2))(2)]
      towards carbon dioxide absorption under supercritical conditions was studied.
      Selective insertion of CO(2) into the amido complex yielded the single-source
      precursor [Er(2)(O(2)CN(2)H(4))Cp(4)], which was characterized by vibrational
      spectroscopy and thermal and elemental analyses. Ammonolysis of this amorphous
      compound at 700 degrees C affords Er(2)O(2)CN(2). To gain deeper insight into the
      structural characteristics of the amorphous precursor, a similar molecular
      carbamato complex was synthesized and fully characterized. X-ray structure
      analysis of the dimeric complex [Cp(4)Ho(2){mu-eta(1):eta(2)-OC(OtBu)NH}] shows
      an unusual bonding mode of the tert-butylcarbamate ligand, which acts as both a
      bridging and side-on chelating group. Ammonolysis of this compound also yielded
      dioxo monocarbodiimides, and therefore the crystalline carbamato complex turned
      out to be an alternative precursor for the straightforward synthesis of
      Ln(2)O(2)CN(2). Analogously, the dioxo monocarbodiimides of Y, Ho, Er, and Yb
      were synthesized by this route. The crystal structures were determined from X-ray
      powder diffraction data and refined by the Rietveld method (Ln=Ho, Er). Further
      spectroscopic characterization and elemental analysis evidenced the existence of
      phase-pure products. The dioxo monocarbodiimides of holmium and erbium
      crystallize in the trigonal space group P[over]3m1. According to X-ray powder
      diffraction, they adopt the Ln(2)O(2)CN(2) (Ln=Ce-Gd) structure type.

PMID- 18058885
TI  - Zn[BPO4(OH)2]: a zinc borophosphate with the rare moganite-type topology.
AB  - A novel zinc borophosphate Zn[BPO(4)(OH)(2)] with moganite-type topology (a rare
      polymorph of silica) has been prepared from a mixture of ZnO, B(2)O(3), and
      P(2)O(5) by hydrothermal treatment at 443 K. The crystal structure was determined
      from single-crystal X-ray data (orthorhombic, Pbcn (no. 60), a=915.07(3),
      b=897.22(3), c=1059.19(3) pm, V=869.62(5)x10(6) pm(3), Z=8, R1=0.028, wR2=0.075).
      The crystal structure comprises unbranched vierer-single borophosphate chains
      running along [010] and interconnected via ZnO(2)(OH)(2)-tetrahedra by sharing
      common vertices. The resulting topology of the three-dimensional tetrahedral
      framework structure is described by the Schlafli symbol
      (4(2).6(2).8(2))(4.6(4).8)(2). Although showing Zn in a tetrahedral coordination,
      the title compound does not belong to the group of zincoborophosphates but is a
      special case of a borophosphate containing vierer single rings of tetrahedra with
      the sequence Zn-B-Zn-P.

PMID- 18058886
TI  - Observation of three intervalence-transfer bands for a class II-III mixed-valence
      complex of ruthenium.

PMID- 18058887
TI  - Experimental evidence that a DNA polymerase can incorporate N7-platinated
      guanines to give platinated DNA.

PMID- 18058888
TI  - Synthesis and characterization of the gold(I) tris(ethylene) complex
      [Au(C2H4)3][SbF6].

PMID- 18058889
TI  - Tailor-made fructooligosaccharides by a combination of substrate and genetic
      engineering.
AB  - The combination of sucrose analogues as novel substrates (substrate engineering)
      and highly active recombinant beta-fructofuranosidase from A. niger (genetic
      engineering) provides a new powerful tool for the efficient preparative synthesis
      of tailor-made saccharides of the important 1-kestose and 1-nystose type headed
      with different monosaccharides of interest. These novel compounds have been
      isolated. They did not display toxic effects or suppress cell growth in initial
      studies, making these new compounds potential candidates for prebiotics.

PMID- 18058890
TI  - Nanopore analysis of a small 86-residue protein.

PMID- 18058891
TI  - Cell specific aptamer-photosensitizer conjugates as a molecular tool in
      photodynamic therapy.

PMID- 18058892
TI  - Genetically encoded bioluminescent indicator for ERK2 dimer in living cells.
AB  - In this study, a genetically encoded bioluminescent indicator for ERK2 dimer was
      developed with the split Renilla luciferase complementation method, in which the
      formation of ERK2 dimer induces a spontaneous emission of bioluminescence in
      living cells. In response to extracellular stimuli, such as epidermal growth
      factor (EGF) or 17beta-estradiol (E2), extracellular signal-regulated kinase 2
      (ERK2) is phosphorylated by its upstream kinase MEK, and also phosphorylates its
      substrates in various regions of the cell, including the nucleus. Phosphorylated
      ERK2 is led to form its dimer, thereby transporting itself into the nucleus. We
      demonstrated with the indicator that stimulation with EGF or E2 induces the
      formation of ERK2 dimer in living MCF-7 cells. The dynamics of this dimer
      formation was examined and discussed.

PMID- 18058895
TI  - Enantio- and diastereoselective syntheses of cyclic Calpha-tetrasubstituted alpha
      amino acids and their use to induce stable conformations in short peptides.
AB  - C(alpha)-tetrasubstituted alpha-amino acids are widely used to design and prepare
      peptides and peptide mimics with constrained conformations. Subcategories of
      these compounds are cyclic C(alpha)-tetrasubstituted alpha-amino acids, in which
      both alpha-substituents are covalently connected. This survey presents recent
      advances in the synthesis and application of cyclic C(alpha)-tetrasubstituted
      alpha-amino acids in a systematic order beginning with cyclopropane amino acids,
      continuing with four, five, six membered rings, and ring structures larger than
      six-membered. We discuss synthetic routes to the cyclic C(alpha)-tetrasubstituted
      alpha-amino acids and their use as conformation determining elements in peptides.

PMID- 18058897
TI  - Effects of supportive-expressive group therapy on survival of patients with
      metastatic breast cancer: a randomized prospective trial.

PMID- 18058898
TI  - Arterial supply to the sciatic nerve in the gluteal region.
AB  - The arterial supply to the sciatic nerve was investigated in 20 human lower limbs
      (10 right, 10 left) from 20 cadavers (14 females, aged 84 +/- 9.6 years, range 66
      95 years: 6 males, aged 80 +/- 8.2 years, range 70-90 years). In all limbs
      examined at least 1 sciatic artery could be identified supplying the sciatic
      nerve in the gluteal region. In total 28 sciatic arteries were identified, of
      which 14 arose from the medial circumflex femoral artery, 11 from the inferior
      gluteal artery, 2 from the first perforating artery, and 1 from the internal
      pudendal artery. In 5 limbs, 2 sciatic arteries were observed, being independent
      branches from the medial circumflex femoral and inferior gluteal arteries in 4
      limbs and separate branches of the medial circumflex femoral artery in 1 limb. In
      1 limb, 4 sciatic arteries were observed: 1 from the inferior gluteal artery, 2
      from the medial circumflex femoral artery, and 1 from the first perforating
      artery. In the remaining 14 limbs a single sciatic artery was observed, which in
      one case arose from the internal pudendal artery, a previously unreported
      observation.

PMID- 18058899
TI  - Parapharyngeal abscess: a life-threatening complication of quinsy.

PMID- 18058900
TI  - Evaluation of methods to reduce formaldehyde levels of cadavers in the dissection
      laboratory.
AB  - Dissection of conventionally embalmed cadavers exposes students, staff, and
      faculty to formaldehyde, a probable carcinogen. Therefore, prudent practices
      should seek to minimize formaldehyde exposure. In this study, we evaluated two
      commercially available chemicals, InfuTrace and Perfect Solution, for their
      effectiveness in reducing ambient formaldehyde levels. Four cadavers embalmed
      conventionally with formaldehyde and/or with the above agents were compared for
      their formaldehyde levels under conditions that strictly controlled for air
      circulation and for locations and methods of testing, and during activities that
      simulated student dissecting. For InfuTrace, one cadaver was reinfused with
      InfuTrace after initial standard perfusion with formaldehyde; a second cadaver
      had InfuTrace injected into the thoracic and abdominal body cavities after
      formaldehyde perfusion. For Perfect Solution, the product was used for embalming
      a third cadaver in lieu of formaldehyde. For a control, a fourth cadaver was
      embalmed with the standard formaldehyde solution. Testing of personal and ambient
      room air samples and of fluid obtained from the cadavers was performed and
      analyzed in a blinded fashion. Results indicated that both Perfect Solution,
      substituted for standard formaldehyde embalming, and InfuTrace infused through
      the vasculature after formaldehyde embalming, resulted in lower concentrations of
      formaldehyde than embalming with formaldehyde solution alone or in combination
      with body cavity injection of InfuTrace. These differences in formaldehyde
      concentrations are consistent across measuring methods, for example, of room air,
      of breathing zone air during cadaver handling and dissection, and of liquid
      samples obtained from the cadavers. Perfect Solution yielded suboptimum fixation
      and a different texture, color, and smell than the formaldehyde treatments.

PMID- 18058901
TI  - Physical injuries in the dissecting room.
AB  - Dissection of human cadavers remains an important element of learning anatomy in
      many medical and dental schools. During this activity, students are introduced to
      the safe handling of surgical instruments. The frequency, type, and mechanism of
      associated injuries are unknown. We undertook a retrospective cohort analysis of
      dissecting-room accidents during a 6-year period (2001-2006). Injury rates were
      adjusted to account for exposure risk. A total of 55 injuries, all minor, were
      recorded in 53 students, representing an overall injury rate of less than 4
      injuries per 1,000 hr of dissection. Twenty-four injuries were documented in
      third-year medical students, 13 in second-year medical students, 10 in second
      year dental students, and 8 in third-year science students. There was a
      statistically significant difference in injury rates between the groups due to a
      higher than expected rate among second-year medical students and a lower than
      expected rate among third-year medical students (P < 0.01). At least 38 (69%)
      injuries were from a scalpel blade. A further three injuries were from bone
      spicules. All except two injuries affected the hand. In conclusion, it is unusual
      for students to injure themselves in the dissecting room. Injuries tend to be
      minor and largely related to scalpel blades. A greater awareness of hazards due
      to sharps and safe handling techniques may reduce the risks of minor injury and
      better prepare students for future clinical practice.

PMID- 18058902
TI  - An unusual supernumerary head of biceps brachii muscle.

PMID- 18058903
TI  - Reclaiming specimens for teaching anatomy in the future.

PMID- 18058904
TI  - Central venous catheterization--an anatomical review of a clinical skill. Part 2.
      Internal jugular vein via the supraclavicular approach.
AB  - The safe and successful performance of a central venous catheterization (CVC)
      requires a specific knowledge of anatomy in addition to a working knowledge.
      Misunderstanding the anatomy may result in failure or complications. This review
      aims to aid understanding of the anatomical framework, pitfalls, and
      complications of CVC of the internal jugular veins. CVC is common practice
      amongst surgeons, anesthesiologists, and emergency room physicians during the
      preparations for major surgical procedures such as open-heart surgery, as well as
      for intensive care monitoring and rapid restoration of blood volume. Associated
      with this technique are certain anatomical pitfalls and complications that can be
      successfully avoided if one possesses a thorough knowledge of the
      contraindications, regional anatomy, and rationale of the technique.

PMID- 18058905
TI  - TransPath: a computational method for locating ion transit pathways through
      membrane proteins.
AB  - The finely tuned structures of membrane channel proteins allow selective passage
      of ions through the available aqueous pores. To understand channel function, it
      is crucial to locate the pores and study their physical and chemical properties.
      Here, we propose a new pore-searching algorithm (TransPath), which uses the
      Configurational Bias Monte Carlo (CBMC) method to generate transmembrane
      trajectories driven by both geometric and electrostatic features. The
      trajectories are binned into groups determined by a vector distance criterion.
      From each group, a representative trajectory is selected based on the Rosenbluth
      weight, and the geometrically optimal path is obtained by simulated annealing.
      Candidate ion pathways can then be determined by analysis of the radius and
      potential profiles. The proposed method and its implementation are illustrated
      using the bacterial KcsA potassium channel as an example. The procedure is then
      applied to the more complex structures of the bacterial E. coli chloride channel
      homolog and a homology model of the ClC-0 channel.

PMID- 18058906
TI  - Optimizing pKa computation in proteins with pH adapted conformations.
AB  - pK(A) in proteins are determined by electrostatic energy computations using a
      small number of optimized protein conformations derived from crystal structures.
      In these protein conformations hydrogen positions and geometries of salt bridges
      on the protein surface were determined self-consistently with the protonation
      pattern at three pHs (low, ambient, and high). Considering salt bridges at
      protein surfaces is most relevant, since they open at low and high pH. In the
      absence of these conformational changes, computed pK(A)(comp) of acidic (basic)
      groups in salt bridges underestimate (overestimate) experimental pK(A)(exp),
      dramatically. The pK(A)(comp) for 15 different proteins with 185 known pK(A)(exp)
      yield an RMSD of 1.12, comparable with two other methods. One of these methods is
      fully empirical with many adjustable parameters. The other is also based on
      electrostatic energy computations using many non-optimized side chain conformers
      but employs larger dielectric constants at short distances of charge pairs that
      diminish their electrostatic interactions. These empirical corrections that
      account implicitly for additional conformational flexibility were needed to
      describe the energetics of salt bridges appropriately. This is not needed in the
      present approach. The RMSD of the present approach improves if one considers only
      strongly shifted pK(A)(exp) in contrast to the other methods under these
      conditions. Our method allows interpreting pK(A)(comp) in terms of pH dependent
      hydrogen bonding pattern and salt bridge geometries. A web service is provided to
      perform pK(A) computations.

PMID- 18058907
TI  - Crystal structure of the catalytic trimer of Methanococcus jannaschii aspartate
      transcarbamoylase.
AB  - The catalytic trimer of Methanococcus jannaschii aspartate transcarbamoylase is
      extremely heat stable, maintaining 75% of its activity after heat treatment for
      60 min at 75 degrees C. We undertook its structural analysis in order to
      understand the molecular basis of its thermostability and gain insight on how its
      catalytic function adapts to high temperature. Several structural elements
      potentially contributing to thermostability were identified. These include: (i)
      changes in the amino acid composition such as a decrease in the thermolabile
      residues Gln and Asn, an increase in the charged residues Lys and Glu, an
      increase in Tyr and a decrease in Ala residues; (ii) a larger number of salt
      bridges, in particular, the improvement of ion-pair networks; (iii) shortening of
      the N-terminus and shortening of three loops. An interesting feature of the
      crystal structure is the association of two crystallographically independent
      catalytic subunits into a staggered complex with an intertrimer distance of 33.8
      A. The active site appears similar to Escherichia coli. Upon substrate binding,
      smaller changes in the global orientation of domains and larger conformational
      changes of the active site residues are expected as compared to E. coli.

PMID- 18058908
TI  - High quality binding modes in docking ligands to proteins.
AB  - Multiple near-optimal conformations of protein-ligand complexes provide a better
      chance for accurate representation of biomolecular interactions, compared with a
      single structure. We present ISE-dock--a docking program which is based on the
      iterative stochastic elimination (ISE) algorithm. ISE eliminates values that
      consistently lead to the worst results, thus optimizing the search for docking
      poses. It constructs large sets of such poses with no additional computational
      cost compared with single poses. ISE-dock is validated using 81 protein-ligand
      complexes from the PDB and its performance was compared with those of Glide,
      GOLD, and AutoDock. ISE-dock has a better chance than the other three to find
      more than 60% top single poses under RMSD = 2.0 A and more than 80% under RMSD =
      3.0 A from experimental. ISE alone produced at least one 3.0 A or better
      solutions among the top 20 poses in the entire test set. In 98% of the examined
      molecules, ISE produced solutions that are closer than 2.0 A from experimental.
      Paired t-tests (PTT) were used throughout to assess the significance of
      comparisons between the performances of the different programs. ISE-dock provides
      more than 100-fold docking solutions in a similar time frame as LGA in AutoDock.
      We demonstrate the usefulness of the large near optimal populations of ligand
      poses by showing a correlation between the docking results and experiments that
      support multiple binding modes in p38 MAP kinase (Pargellis et al., Nat Struct
      Biol 2002;9:268-272] and in Human Transthyretin (Hamilton, Benson, Cell Mol Life
      Sci 2001;58:1491-1521).

PMID- 18058909
TI  - Effect of oxidatively damaged DNA on the active site preorganization during
      nucleotide incorporation in a high fidelity polymerase from Bacillus
      stearothermophilus.
AB  - We study the effect of the oxidative lesion 8-oxoguanine (8oxoG) on the
      preorganization of the active site for DNA replication in the closed (active)
      state of the Bacillus fragment (BF), a Klenow analog from Bacillus
      stearothermophilus. Our molecular dynamics and free energy simulations of
      explicitly solvated model ternary complexes of BF bound to correct dCTP/incorrect
      dATP opposite guanine (G) and 8oxoG bases in DNA suggest that the lesion
      introduces structural and energetic changes at the catalytic site to favor dATP
      insertion. Despite the formation of a stable Watson-Crick pairing in the
      8oxoG:dCTP system, the catalytic geometry is severely distorted to possibly slow
      down catalysis. Indeed, our calculated free energy landscapes associated with
      active site preorganization suggest additional barriers to assemble an efficient
      catalytic site, which need to be overcome during dCTP incorporation opposite
      8oxoG relative to that opposite undamaged G. In contrast, the catalytic geometry
      for the Hoogsteen pairing in the 8oxoG:dATP system is highly organized and poised
      for efficient nucleotide incorporation via the "two-metal-ion" catalyzed
      phosphoryl transfer mechanism. However, the free energy calculations suggest that
      the catalytic geometry during dATP incorporation opposite 8oxoG is considerably
      less plastic than that during dCTP incorporation opposite G despite a very
      similar, well organized catalytic site for both systems. A correlation analysis
      of the dynamics trajectories suggests the presence of significant coupling
      between motions of the polymerase fingers and the primary distance for
      nucleophilic attack (i.e., between the terminal primer O3' and the dNTP P(alpha.)
      atoms) during correct dCTP incorporation opposite undamaged G. This coupling is
      shown to be disrupted during nucleotide incorporation by the polymerase with
      oxidatively damaged DNA/dNTP substrates. We also suggest that the lesion affects
      DNA interactions with key polymerase residues, thereby affecting the enzymes
      ability to discriminate against non-complementary DNA/dNTP substrates. Taken
      together, our results provide a unified structural, energetic, and dynamic
      platform to rationalize experimentally observed relative nucleotide incorporation
      rates for correct dCTP/incorrect dATP insertion opposite an undamaged/oxidatively
      damaged template G by BF.

PMID- 18058910
TI  - Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and
      duodenum.
AB  - Pax4-deficient mice have a severe gastrointestinal endocrine deficiency: they
      lack most pancreatic cells that produce insulin or somatostatin and various
      duodenal endocrine cell types. Remarkably, Pax4-deficient mice also have an
      overabundance of ghrelin-expressing cells in the pancreas and duodenum. Detailed
      analysis of the Pax4 nullizygous pancreas determined that the mutant islets are
      largely composed of a distinctive endocrine cell type that expresses ghrelin,
      glucagon, islet amyloid polypeptide (IAPP), and low levels of Pdx1. Lineage
      tracing analysis revealed that most of these unique endocrine cells directly
      arose from Pax4-deficient progenitors. Previous in vitro work reported that Pax4
      is a transcriptional repressor of islet amyloid polypeptide (IAPP) and glucagon.
      In this study, we expanded those results by showing that Pax4 is also a repressor
      of gherlin. Together, our data further support the notion that Pax4 activity is
      necessary to establish appropriate patterns of gene expression in endocrine
      progenitors of the digestive tract.

PMID- 18058911
TI  - Beta1 integrin expression on endothelial cells is required for angiogenesis but
      not for vasculogenesis.
AB  - Integrins are a family of cell adhesion receptors that are involved in cell
      matrix and cell-cell communications. They facilitate cell proliferation,
      migration, and survival. Using the Cre-Lox system, we deleted beta1 integrin on
      Tie2-positive (Tie2-cre beta1 Int (fl/fl)) vascular endothelial cells. Deletion
      of beta1 integrin on vascular endothelial cells results in embryonic lethality.
      Blood vessel defects are encountered in the Tie2-Cre beta1 Int (fl/fl) embryos at
      embryonic age (E9.5), and embryos die before reaching E10.5. The embryos exhibit
      growth retardation and both histological evaluation and PECAM-1 staining of E9.5
      embryos revealed defects in angiogenic sprouting and vascular branching
      morphogenesis. Large and medium-size vessel formation is not affected in these
      embryos. Angiogenic defects were observed in several regions of the embryo and
      yolk sacs. These results indicate that beta1 integrin expression on vascular
      endothelial cells is crucial for embryonic angiogenesis but dispensable for
      vasculogenesis.

PMID- 18058912
TI  - Functional evolutionary history of the mouse Fgf gene family.
AB  - Fibroblast Growth Factors (FGFs) are polypeptides with diverse activities in
      development and physiology. The mammalian Fgf family can be divided into the
      intracellular Fgf11/12/13/14 subfamily (iFGFs), the hormone-like Fgf15/21/23
      subfamily (hFGFs), and the canonical Fgf subfamilies, including Fgf1/2/5,
      Fgf3/4/6, Fgf7/10/22, Fgf8/17/18, and Fgf9/16/20. However, all Fgfs are
      evolutionarily related. We propose that an Fgf13-like gene is the ancestor of the
      iFgf subfamily and the most likely evolutionary ancestor of the entire Fgf
      family. Potential ancestors of the canonical and hFgf subfamilies, Fgf4-, Fgf5-,
      Fgf8-, Fgf9-, Fgf10-, and Fgf15-like, appear to have derived from an Fgf13-like
      ancestral gene. Canonical FGFs function in a paracrine manner, while hFGFs
      function in an endocrine manner. We conclude that the ancestral Fgfs for these
      subfamilies acquired this functional diversity before the evolution of
      vertebrates. During the evolution of early vertebrates, the Fgf subfamilies
      further expanded to contain three or four members in each subfamily.

PMID- 18058913
TI  - Nuclear localization of the zebrafish tight junction protein nagie oko.
AB  - The tight junctions-associated MAGUK protein nagie oko is closely related to
      Drosophila Stardust, mouse protein associated with lin-seven 1 (Pals1), and human
      MAGUK p55 subfamily member 5 (Mpp5). As a component of the evolutionarily
      conserved Crumbs protein complex, nagie oko is essential for the maintenance of
      epithelial cell polarity. Here, we show that nagie oko contains a predicted
      nuclear export and two conserved nuclear localization signals. We find that loss
      of the predicted nuclear export signal results in nuclear protein accumulation.
      We show that nagie oko nuclear import is redundantly controlled by the two
      nuclear localization signals and the evolutionarily conserved region 1 (ECR1),
      which links nagie oko with Par6-aPKC. Finally, deletion forms of nagie oko that
      lack nuclear import and export signals complement several nagie oko mutant
      defects in cell polarity and epithelial integrity. This finding provides an entry
      point to potentially novel and unknown roles of this important cell polarity
      regulator.

PMID- 18058914
TI  - Biological spacetime and the temporal integration of functional modules: a case
      study of dento-gnathic developmental timing.
AB  - For the individual, coordination between tooth and jaw development is important
      to proper food acquisition and ingestion later in life. Among and within species,
      variation in dental and gnathic size, shape, and, in the case of teeth, number,
      must be mutually accommodating and functionally compatible. For these reasons,
      the development and evolution of these two systems should be closely integrated.
      Furthermore, the timing of dental development correlates tightly with life
      history events such as weaning. This correlation hints at a central regulation of
      the developmental timing of multiple systems that have tandem effects on
      physiology and behaviour. Important work on embryonic oral development continues
      to tease apart the molecular mechanisms that pattern jaw identity and establish
      tooth morphology and position in the alveolar bone. Still very poorly understood
      is what underlies rates and periods of gene activity such that pre- and postnatal
      tooth and jaw development are coordinated. Recent literature suggests at least
      some level of autonomy between permanent tooth and mandibular ontogenetic timing.
      However, whether the timing of these various signaling pathways is directly
      regulated or is an outcome of the pathways themselves is untested. Here, we
      review what is currently known about the embryonic signaling pathways that
      regulate tooth and jaw development in the context of time rather than space, as
      has been traditional. We hypothesize that the timing of mandibular and dental
      development is not directly mediated by a common factor but is an indirect
      outcome of strong selection for coordinated molecular pathways and growth
      trajectories. The mandible and lower jaw dentition is a powerful model with which
      to investigate the mechanisms that facilitate morphological change-in this case,
      the development and evolution-of organs that are closely integrated in terms of
      function, space and time.

PMID- 18058915
TI  - Midkine-b regulates cell specification at the neural plate border in zebrafish.
AB  - Midkines compose a family of secreted, heparin-binding growth factors with
      neurotrophic activity in vitro, but largely unknown functions in mammals in vivo.
      Here we show that one member of this family, Midkine-b (Mdkb), is responsible for
      establishment of the neural plate border in zebrafish. We propose that MdkB acts
      downstream of several signaling factors, most notably retinoic acid, implicated
      in neural crest cell (ncc) induction and refines a zone of competence for ncc and
      Rohon-Beard (RB) sensory neuron formation. Overexpression of Mdkb expands the
      cell numbers of various ncc precursor subtypes and results in a significant
      increase in the number of RB neurons at the neural plate border. On the other
      hand, Morpholino-mediated knockdown of Mdkb leads to a dramatic reduction of ncc
      and a loss of sensory neurons. Our results imply that Mdkb is required for the
      earliest steps of cell specification at the neural plate border in zebrafish.

PMID- 18058916
TI  - Temporal-spatial ablation of neural crest in the mouse results in cardiovascular
      defects.
AB  - Neural crest cells are thought to play a critical role in human conotruncal
      morphogenesis and dysmorphogenesis. Much of our understanding of the contribution
      of neural crest to cardiovascular patterning comes from ablation and
      transplantation experiments in avian species. Although fate mapping experiments
      in mice suggests a conservation of function, the functional requirement for
      neural crest in cardiovascular development in mammals has not been formally
      tested. We used a novel two component genetic system for the temporal-spatial
      ablation of neural crest in the mouse. Affected embryos displayed a spectrum of
      cardiovascular outflow tract defects and aortic arch patterning abnormalities. We
      show that the severity of the cardiovascular phenotype is directly related to the
      level and extent of neural crest ablation. This is the first report of cardiac
      neural crest ablation in mammals, and it provides important insight into the role
      of the mammalian neural crest during cardiovascular development.

PMID- 18058917
TI  - Capital punishment and anatomy: history and ethics of an ongoing association.
AB  - Anatomical science has used the bodies of the executed for dissection over many
      centuries. As anatomy has developed into a vehicle of not only scientific but
      also moral and ethical education, it is important to consider the source of human
      bodies for dissection and the manner of their acquisition. From the thirteenth to
      the early seventeenth century, the bodies of the executed were the only legal
      source of bodies for dissection. Starting in the late seventeenth century, the
      bodies of unclaimed persons were also made legally available. With the developing
      movement to abolish the death penalty in many countries around the world and with
      the renunciation of the use of the bodies of the executed by the British legal
      system in the nineteenth century, two different practices have developed in that
      there are Anatomy Departments who use the bodies of the executed for dissection
      or research and those who do not. The history of the use of bodies of the
      executed in German Anatomy Departments during the National Socialist regime is an
      example for the insidious slide from an ethical use of human bodies in dissection
      to an unethical one. There are cases of contemporary use of unclaimed or donated
      bodies of the executed, but they are rarely well documented. The intention of
      this review is to initiate an ethical discourse about the use of the bodies of
      the executed in contemporary anatomy.

PMID- 18058918
TI  - Zebrafish mutants as models for congenital ocular disorders in humans.

PMID- 18058921
TI  - 4-hydroxynonenal: a membrane lipid oxidation product of medicinal interest.
AB  - A comprehensive focus on 4-hydroxynonenal (HNE) as candidate molecule in a
      variety of pathophysiological conditions occurring in humans is here provided.
      Despite an active, now well characterized, metabolism in most cells and tissues,
      HNE can be easily detected and quantified by means of several methods, although
      with different sensitivity. Measurements of HNE and/or stable metabolites in
      biological fluids are already applied as lipid peroxidation/oxidative stress
      markers in a huge number of human disease processes, often sustained by
      inflammatory reactions. A primary involvement of this aldehydic product of
      membrane lipid oxidation in inflammation-related events, as well as in regulation
      of cell proliferation and growth, in necrotic or apoptotic cell death, appears
      supported by its marked ability to modulate several major pathways of cell
      signaling and, consequently, gene expression. The actual knowledge of HNE
      reactivity, metabolism, signaling and modulatory effect in the various human
      organs should provide a solid background to the investigation of the aldehyde's
      contribution to the pathogenesis of human major chronic diseases and would likely
      promote advanced and oriented applications not only in diagnosis and prevention
      but also in molecular treatment of human diseases.

PMID- 18058922
TI  - Expression of ERK signaling inhibitors Dusp6, Dusp7, and Dusp9 during mouse ear
      development.
AB  - The levels of fibroblast growth factor (FGF) signaling play important roles in
      coordinating development of the mouse inner, middle, and outer ears.
      Extracellular signal-regulated kinases (ERKs) are among the effectors that
      transduce the FGF signal to the nucleus and other cellular compartments.
      Attenuation of ERK activity by dephosphorylation is necessary to modulate the
      magnitude and duration of the FGF signal. Recently, we showed that inactivation
      of the ERK phosphatase, dual specificity phosphatase 6 (DUSP6), causes partially
      penetrant postnatal lethality, hearing loss and skeletal malformations. To
      determine whether other Dusps may function redundantly with Dusp6 during otic
      development, we surveyed the expression domains of the three ERK-specific DUSP
      transcripts, Dusp6, Dusp7, and Dusp9, in the embryonic mouse ear. We show that
      each is expressed in partially overlapping patterns that correspond to regions of
      active FGF signaling, suggesting combinatorial roles in negative regulation of
      this pathway during ear development.

PMID- 18058923
TI  - Differential growth and multicellular villi direct proepicardial translocation to
      the developing mouse heart.
AB  - In the mammalian system the proepicardium (PE) arises from mesothelium of the
      septum transversum before translocation to the heart where it forms the
      epicardium and progenitor cells of the coronary vessels. Despite its importance,
      the process in which PE cells translocate to the myocardium in mammals is not
      well defined. The current paradigm states that cellular cysts of PE float across
      the pericardial space and contact the outer surface of the myocardium. This
      mechanism does not provide a satisfactory explanation for the directionality or
      localization of PE migration. To better define PE migration, we performed a
      detailed study of mouse PE development. We provide thorough documentation that
      redefines the size of the PE migratory field and the mechanism of migration. Our
      new model incorporates differential growth and direct contact between
      multicellular PE villi and the myocardium as mechanisms in formation of the
      epicardium.

PMID- 18058925
TI  - Prolonged glucocorticoid treatment decreases cannabinoid CB1 receptor density in
      the hippocampus.
AB  - Experimental studies indicate a bidirectional, functional relationship between
      glucocorticoids and the endocannabinoid system; however, the effects of repeated
      glucocorticoid treatment on the endocannabinoid system have not been examined. In
      this study, we treated male rats with either a single dose or a 21-day course of
      treatment with corticosterone (20 mg/kg) and measured hippocampal cannabinoid
      CB(1) receptor expression and endocannabinoid content. The 21-day, but not the
      single, administration of corticosterone significantly reduced both the binding
      site density and amount of protein of the hippocampal cannabinoid CB(1) receptor
      without affecting affinity for the CB(1) receptor agonist, [(3)H]CP55940. With
      regard to hippocampal endocannabinoid content, acute corticosterone treatment
      resulted in a significant reduction in anandamide but did not affect 2
      arachidonylglycerol, while repeated corticosterone treatment did not alter
      content of either anandamide or 2-arachidonylglycerol. These data support the
      hypothesis that the cannabinoid CB(1) receptor is under negative regulation by
      glucocorticoids in the hippocampus, and suggest that hippocampal cannabinoid
      CB(1) receptor signaling could be reduced under conditions associated with
      hypersecretion of glucocorticoids, such as chronic stress.

PMID- 18058926
TI  - Measurement of longitudinal (T1) relaxation in the human lung at 3.0 Tesla with
      tissue-based and regional gradient analyses.
AB  - PURPOSE: The purpose of this study is to measure the longitudinal (T1) relaxation
      time of human lung parenchyma at 3.0 Tesla (T), independent of large vessel
      signal, and to examine T1 as a function of position in gravitational,
      isogravitational, and radial planes. MATERIALS AND METHODS: Sixteen subjects were
      imaged. A series of 16-20 turbo field echo images was acquired over a 6-s period
      after the application of a single nonselective inversion (180 degrees ) pulse.
      Tissue-based segmentation was used to separate parenchymal tissue from large
      pulmonary vascular tissue in the resulting images. Time-intensity curves for each
      tissue type were constructed and spin-lattice relaxation time was determined by
      line-fitting the time-intensity curves. The lung slice was divided into 10
      regions of interest in the gravitational, isogravitational, and radial directions
      and regional T1 versus position gradient analyses were performed. RESULTS: The T1
      relaxation time of human lung parenchyma at 3.0T was determined to be 1374 +/-
      226 ms, while the T1 of blood in large pulmonary vessels was 1623 +/- 236 ms.
      Whole lung T1 was found to be 1397 +/- 214 ms. T1 of lung parenchyma was found to
      be significantly shorter than the T1 of blood in large pulmonary vessels and
      whole lung T1. No regional gradient was seen in the gravitational or
      isogravitational directions, but a significant gradient was seen in the radial
      direction.

PMID- 18058927
TI  - Suspected chronic pancreatitis with normal MRCP: findings on MRI in correlation
      with secretin MRCP.
AB  - PURPOSE: To review pancreatic MRI findings and their relationship with estimated
      pancreatic exocrine function on secretin-stimulated MR cholangiopancreatography
      (S-MRCP) in patients with clinically suspected chronic pancreatitis and normal
      baseline MRCP findings. MATERIALS AND METHODS: MRI findings of 26 patients with
      normal pancreatic duct diameter and without side branch ectasia on MRCP were
      evaluated. A single radiologist assessed pancreatic size, pancreatic signal
      intensity ratio (SIR), and arterial enhancement ratio (A/V) at head, body, and
      tail of the pancreas on T(1)-weighted fat-suppressed and serial contrast-enhanced
      images at a single session. Combined findings were graded with a composite score.
      Serial S-MRCP was performed at the same session with standard MRI. Correlation
      and differences between MRI findings and associated grade of duodenal filling
      (DF) or the degree of pancreatic duct caliber change (PDC) were analyzed.
      RESULTS: Seven patients revealed normal and 19 patients abnormal MRI findings.
      Significant correlation was present between the degree of DF and mean values of
      pancreatic size (r = 0.748), SIR (r = 0.610), A/V (r = 0.466), composite score (r
      = 0.833), and PDC (r = 0.554) separately. PDC correlated with SIR (r = 0.413) and
      composite score (r = 0.452), but not with A/V or pancreatic size. Significant
      differences were present between normal and abnormal DF grades in terms of mean
      values of associated findings of size (P = 0.001), SIR (P = 0.008), A/V (P =
      0.019), and PDC (P = 0.001). CONCLUSION: Patients with clinically suspected
      chronic pancreatitis and normal MRCP findings may have a spectrum of MRI findings
      that correlate with the estimated pancreatic exocrine insufficiency on S-MRCP
      with the increasing number of combined findings.

PMID- 18058928
TI  - Improvement in the reproducibility of region of interest using an auditory
      feedback loop: a pilot assessment using dynamic contrast-enhanced (DCE) breast MR
      images.
AB  - PURPOSE: To augment traditional visual data perception of complex multiparametric
      imaging data sets by adding auditory feedback to improve the delineation of
      regions of interest (ROIs) in tumor assessment in dynamic contrast-enhanced (DCE)
      MRI. MATERIALS AND METHODS: In addition to conventional display methodologies, we
      have created an application window which interfaces with audio output using
      dynamically loadable sound modules, providing goodness of fit (GF) information
      through auditory feedback. We have assessed effectiveness of conveying sound
      information with three independent readers on eight DCE-MR breast image data
      sets. The assessment was based on either conventional visual only mode or
      combined visual plus auditory mode. For statistical comparison between two
      sensory approaches, interobserver repeatability was measured with three different
      criteria. RESULTS: Adding auditory feedback improves repeatability significantly
      (P < 0.01), and the enhanced sensory approach had higher repeatability than
      visual only mode in visually complex breast tumor cases. However, in easy and
      moderate cases, visual only mode was more reproducible than the combined mode
      with very high significance (P < 0.001). CONCLUSION: Adding auditory information
      to visual based image analysis for identifying tumor ROIs provides higher
      interobserver repeatability for analyzing complex
      multidimensional/multiparametric medical image data sets with visually difficult
      lesions to delineate.

PMID- 18058929
TI  - MR angiography of the pedal arteries with gadobenate dimeglumine, a contrast
      agent with increased relaxivity, and comparison with selective intraarterial DSA.
AB  - PURPOSE: To compare gadobenate dimeglumine (Gd-BOPTA)-enhanced MR angiography
      (i.e., contrast-enhanced MRA [CE-MRA]) of the pedal vasculature with selective
      digital subtraction angiography (DSA) in patients with peripheral arterial
      occlusive disease (PAOD). MATERIALS AND METHODS: A total of 22 patients with PAOD
      were prospectively examined at 1.5T. For contrast enhancement, 0.1 mmol/kg body
      weight of Gd-BOPTA were applied. MRA consisted of dynamic imaging with
      acquisition of six consecutive data sets. Acquisition time for each data set was
      24 seconds, voxel size was 1.0 x 1.0 x 1.3 mm(3). A total of 20 out of 22 patient
      underwent selective DSA, two patients fine-needle DSA. DSA and MRA were performed
      within seven days. Image analysis was independently done by two observers with
      assessment of overall image quality, motion artifacts, detection of patent vessel
      segments of the distal calf and pedal vessels, and the number of patent
      metatarsal arteries. After four weeks, a consensus reading of DSA images was
      done. A second consensus reading of CE-MRA was performed after a further six
      weeks. RESULTS: Consensus readings of MRA and DSA revealed higher image quality
      and fewer motion artifacts for MRA (P = 0.021 and P = 0.008, respectively, sign
      test); interobserver agreement was good (kappa = 0.78) for image quality, and
      moderate (kappa = 0.46) for motion artifacts. There were no differences between
      CE-MRA and DSA in detecting patent vessel segments with a high degree of
      agreement (kappa = 0.89), and interobserver agreement for MRA was substantial
      (kappa = 0.89). Significantly more vessels were assessed as partially occluded on
      DSA than on CE-MRA (P = 0.004). There was a good agreement between DSA and CE-MRA
      for assessment of relevant vessel stenosis (kappa = 0.61); interobserver
      agreement for MRA was good (kappa = 0.65). CE-MRA detected significantly more
      patent metatarsal arteries than did DSA (P < 0.001). CONCLUSION: Gd-BOPTA
      enhanced MRA is comparable to DSA for assessment of the pedal vasculature, and is
      able to delineate significantly more patent vessels without segmental occlusions
      and more metatarsal arteries than selective DSA.

PMID- 18058930
TI  - Complications and limitations related to periprostatic local anesthesia before
      TRUS-guided prostate biopsy.
AB  - PURPOSE: To assess the frequency of complications specifically related to local
      anesthetic infiltration prior to transrectal ultrasound (TRUS)-guided prostate
      biopsy. METHODS: A total of 200 patients receiving 10 cm(3) (5 cm(3) on each
      side) of 2% lidocaine injected around the periprostatic nerve plexus under TRUS
      guidance before prostate biopsy were included. Various complications presumed to
      be associated with local anesthesia were noted during and after the biopsy
      procedure. Two weeks later, periprostatic tissue integrity and vascularization
      were re-examined with TRUS Doppler examination to assess for fibrosis or
      infection. RESULTS: The most common finding was pain due to puncture with the
      needle used for local anesthesia (27%). Also recorded were the need for repeated
      injections during the biopsy procedure (4.5%), symptoms associated with systemic
      lidocaine toxicity (2%), urinary incontinence (1.5%), and degradation of the
      image resolution due to anesthetic injection (1%). Increased vascularization
      within the periprostatic region was uncommon (2%) on the 2-week follow-up
      examination. No TRUS finding consistent with rectal wall hematoma or other
      periprostatic change and no erectile dysfunction associated with the procedure
      occurred. There was a significant difference in overall pain scores between the
      subgroups of patients (p < 0.001). CONCLUSION: TRUS-guided periprostatic nerve
      blockade is an effective method for relieving discomfort from prostate biopsy
      with very few complications.

PMID- 18058931
TI  - Renal and carotid vascular resistance assessed with Doppler sonography.
AB  - PURPOSE: Resistance index (RI) is widely used for the evaluation of circulatory
      resistance and atherosclerosis with Doppler sonography, but differences in RI
      among vascular beds have not been fully elucidated. The present study was
      designed to evaluate the relationship between renal and carotid artery RI and to
      compare their relative risk factors for an increase in RI. METHODS: One hundred
      eighty-five inpatients who underwent sonographic assessment of the renal and
      carotid arteries were enrolled in the study. RESULTS: Multivariate analyses
      revealed that age, pulse pressure (PP), and serum glucose level were positively
      correlated, whereas diastolic blood pressure (DBP) and creatinine clearance were
      negatively correlated with the RI of the interlobar arteries. Sex (male) and PP
      correlated positively, whereas DBP correlated negatively with the RI of the
      common carotid artery (CCA). The RI of the interlobar arteries was positively
      associated with that of the CCA, even after adjustment for major cardiovascular
      risk factors. CONCLUSIONS: These findings suggest that RI of the renal and
      carotid arteries increase in parallel to a certain extent. On the other hand,
      risk factors for the increase of RI of the carotid and renal arteries differed in
      part, suggesting that specific control of respective risk factors may also be
      needed to prevent vascular damage in each vascular bed.

PMID- 18058932
TI  - Apparent T(2) relaxation times of lipid and macromolecules: a study of high-grade
      tumor spectra.
AB  - PURPOSE: To determine T(2) relaxation times of lipid and macromolecules (Lip/MMs)
      observed by (1)H magnetic resonance spectroscopy ((1)H MRS) of metastases (MET)
      and glioblastomas (GBM), so that they may be better characterized. MATERIALS AND
      METHODS: (1)H spectra were acquired at multiple echo times from brain lesions
      using point-resolved spectroscopy sequence (PRESS) at TE = 30 msec either with
      metabolite-nulling (six GBM and 11 MET), or without metabolite-nulling (four MET
      and one mucocele). All lesions were previously untreated and had subsequent
      histopathological classification. RESULTS: The T(2) of the 1.3-ppm Lip/MM peak
      was concentration-dependent, but at high concentrations it was significantly
      different (P = 0.015) between GBM (42 +/- 6 msec) and MET (63 +/- 18 msec). The
      broad 2.05-ppm and 0.09-ppm Lip/MM peaks had similar T(2)s in MET and GBM. The
      T(2) of the narrow 2.05-ppm Lip/MM peak sometimes observed had a T(2) of 100 +/-
      17 msec in MET and 75 msec in the mucocele. CONCLUSION: We observed significantly
      higher T(2) of the 1.3-ppm Lip/MM peak in MET compared with GBM at high 1.3-ppm
      proton concentrations, in agreement with a higher 1.3/0.9-ppm peak ratio found in
      MET. The relatively long T(2) of the 2.05-ppm Lip/MM peak sometimes observed in
      MET may cause it to be confused with N-acetyl aspartate (NAA).

PMID- 18058933
TI  - Echo-planar imaging for MRI evaluation of intrathoracic tumors in murine models
      of lung cancer.
AB  - PURPOSE: To evaluate the efficacy of fast cardiac- and respiratory-gated MRI
      acquisition methods for noninvasive assessment of tumor volume in murine models
      of lung cancer. MATERIALS AND METHODS: A total of 21 mice bearing either human
      small-cell (N417) or non-small-cell (H460) lung tumors were scanned using
      combinations of respiratory-gated computed tomography (CT) imaging, cardiac- and
      respiratory-gated multishot spin-echo echo-planar imaging (SE-EPI), and cardiac-
      and respiratory-gated spoiled gradient echo (SPGR). Tumor depiction at 4.7T was
      qualitatively and quantitatively compared with CT and tissue cross sections. MRI
      based measures of tumor volume were compared with ex vivo measurement of tumor
      mass. RESULTS: Tumors appeared hyperintense on T(2)-weighted EPI images,
      providing positive intrinsic contrast between tumors and surrounding tissues.
      Tumor boundaries were better distinguished by EPI and SPGR with T(1)-reducing
      contrast enhancement when tumor abutted other tissues than by CT or SPGR without
      contrast. Tumor volumes measured from EPI images correlate well with ex vivo
      measurements of tumor mass (P < 0.001, r(2) = 0.99) and volume (P < 0.01, r(2) =
      0.98) over a wide range of tumor sizes. CONCLUSION: Respiratory- and cardiac
      gated multishot EPI enables accurate, noninvasive assessment of tumor in murine
      models of lung cancer using a sequence that requires approximately two minutes to
      complete.

PMID- 18058934
TI  - Extending slice coverage for breathhold fat-suppressed T2-weighted fast spin-echo
      of the liver at 3.0T: application of variable-rate selective-excitation (VERSE)
      RF pulses.
AB  - PURPOSE: To determine the benefits of variable-rate selective-excitation (VERSE)
      radio frequency (RF) pulses for increased slice coverage in breathhold (BH) fat
      suppressed T2-weighted fast spin-echo (FS-T2W-FSE) liver imaging at 3.0T.
      MATERIALS AND METHODS: A total of 12 healthy volunteers were imaged on 3.0T,
      using FS-T2W-FSE. Slice coverage and specific absorption rate (SAR) levels were
      monitored for VERSE-RF and standard-RF (sRF), respectively. BH time was 25
      seconds; slice thickness 3.5 mm. Maximum coverage was recorded for interactive
      variation of repetition time (TR), bandwidth (BW), and echo-train length (ETL).
      Image quality was assessed qualitatively and quantitatively. RESULTS: Total slice
      coverage was always higher using VERSE-RF, but varied depending on the selected
      parameters. For BW > or = 62.5 kHz, slice coverage using VERSE increased between
      38% (TR = 8200 msec) and 58% (TR = 2500 msec). Maximum coverage was obtained for
      TR = 5000 msec, ETL = 12, and BW > or = 62.5 kHz; with a mean of 31.8 slices for
      VERSE-RF and 22.5 slices for sRF, respectively (P < 0.005, 41% increased
      coverage). SAR was lower for VERSE-RF using BW < 41.67 kHz (P < 0.05), and equal
      to sRF for higher BW. Image quality was best for TR < or = 5000 msec (P < 0.05).
      FS was more homogeneous for lower ETL (P < 0.05). Blood suppression was best for
      TR < or = 5000 msec (P < 0.05). CONCLUSION: VERSE-RF pulses can be applied for
      thin-slice BH FS-T2W liver imaging at 3.0T, with significantly improved slice
      coverage.

PMID- 18058935
TI  - On optimality of parallel MRI reconstruction in k-space.
AB  - Parallel MRI reconstruction in k-space has several advantages, such as tolerance
      to calibration data errors and efficient non-Cartesian data processing. These
      benefits largely accrue from the approximation that a given unsampled k-space
      datum can be synthesized from only a few local samples. In this study, several
      aspects of parallel MRI reconstruction in k-space are studied: the design of
      optimized reconstruction kernels, the effect of regularization on image error,
      and the accuracy of different k-space-based parallel MRI methods. Reconstruction
      of parallel MRI data in k-space is posed as the problem of approximating the
      pseudoinverse with a sparse matrix. The error of the approximation is used as an
      optimization criterion to find reconstruction kernels optimized for the given
      coil setup. An efficient algorithm for automatic selection of reconstruction
      kernels is described. Additionally, a total error metric is introduced for
      validation of the reconstruction kernel and choice of regularization parameters.
      The new methods yield reduced reconstruction and noise errors in both simulated
      and real data studies when compared with existing methods. The new methods may be
      useful for reduction of image errors, faster data processing, and validation of
      parallel MRI reconstruction design for a given coil system and k-space
      trajectory.

PMID- 18058936
TI  - MR elastography of the lung with hyperpolarized 3He.
AB  - MR elastography (MRE) is a phase contrast-based technique for spatially mapping
      the mechanical properties of tissue-like materials. While hyperpolarized noble
      gases such as helium-3 ((3)He) have proven to be an ideal contrast mechanism for
      imaging of the lung using conventional MR techniques, their applicability for
      lung MRE is unknown, due to the fact that gases do not support shear. In this
      study, we report on the application of MRE to an ex vivo porcine lung specimen
      inflated with a hyperpolarized noble gas. Unlike proton MRE, shear wave
      propagation is encoded into the gas entrapped within the alveolar spaces rather
      than the parenchyma itself. These data provide first evidence of the technical
      feasibility of MRE of the lung using hyperpolarized noble gases.

PMID- 18058937
TI  - Imaging cadavers: cold FLAIR and noninvasive brain thermometry using CSF
      diffusion.
AB  - There is increasing interest in imaging cadavers for noninvasive autopsies for
      research purposes. However, the temperature is well below that of in vivo
      imaging, and a variety of interesting 'cold brain' effects are observed. At lower
      temperatures conventional FLAIR sequences no longer produce dark cerebrospinal
      fluid (CSF); T(1) is reduced from about 4.0 sec in vivo to 1.7 sec at 1 degrees
      C. The diffusion coefficient (DC) of CSF is much reduced (from 3.1 10(-9) m(2)s(
      1) in vivo to 1.1 at 1 degrees C). DC values therefore provide a noninvasive
      thermometer to measure brain core temperature to within 1.0 degrees C. In three
      cadavers DC values were 1.1-1.5 10(-9) m(2)s(-1), indicating brain core
      temperatures of 1-10 degrees C, consistent with external thermocouple
      measurements. An improved inversion time (TI(0)) can then be found for FLAIR. At
      10 degrees C this Cold FLAIR sequence (TI(0) = 1.5 sec) gave black CSF.
      Expressions for CSF DC and T(1) as a function of temperature were produced. A
      measurement of CSF DC could be converted directly to temperature and the required
      TI(0) found. In vitro values of CSF DC were about 1% lower than that of water.
      Thus, FLAIR imaging can be optimized for cadaveric brains at low and unknown
      temperatures, thereby improving value for autopsy purposes and facilitating
      comparisons with in vivo imaging.

PMID- 18058938
TI  - Unsupervised estimation of myocardial displacement from tagged MR sequences using
      nonrigid registration.
AB  - We propose a fully automatic cardiac motion estimation technique that uses
      nonrigid registration between temporally adjacent images to compute the
      myocardial displacement field from tagged MR sequences using as inputs (sources)
      both horizontally and vertically tagged images. We present a new multisource
      nonrigid registration algorithm employing a semilocal deformation model that
      provides controlled smoothness. The method requires no segmentation. We apply a
      multiresolution optimization strategy for better speed and robustness. The
      accuracy of the algorithm is assessed on experimental data (animal model) and
      healthy volunteer data by calculating the root mean square (RMS) difference in
      position between the estimated tag trajectories and manual tracings outlined by
      an expert. For the approximately 20000 tag lines analyzed (45 slices over 20-40
      time frames), the RMS difference between the automatic tag trajectories and the
      manually segmented tag trajectories was 0.51 pixels (0.25 mm) for the animal data
      and 0.49 pixels (0.49 mm) for the human volunteer data. The RMS difference in the
      separation between adjacent tag lines (RMS_TS) was also assessed, resulting in an
      RMS_TS of 0.40 pixels (0.19 mm) in the experimental data and 0.52 pixels (0.56
      mm) in the volunteer data. These results confirm the subpixel accuracy achieved
      using the proposed methodology.

PMID- 18058939
TI  - Iterative projection reconstruction of time-resolved images using highly
      constrained back-projection (HYPR).
AB  - Highly-constrained back-projection (HYPR) is a technique for the reconstruction
      of sparse, highly-undersampled time-resolved image data. A novel iterative HYPR
      (I-HYPR) algorithm is presented and validated in computer simulations. The
      reconstruction method is then applied to cerebral perfusion MRI simulated as a
      radial acquisition and contrast-enhanced angiography of the head to assess
      feasibility in accelerating acquisitions requiring high temporal resolution and
      accurate representation of contrast kinetics. The I-HYPR algorithm is shown to be
      more robust than standard HYPR in these applications in which the sparsity
      condition is not met or in which quantitative information is required.
      Specifically, iterative reconstruction of undersampled perfusion and contrast
      enhanced angiography data improved accuracy of the representation of contrast
      kinetics and increased the temporal separation of arterial and venous contrast
      kinetics. The I-HYPR reconstruction may have important diagnostic applications in
      settings requiring high temporal resolution and quantitative signal dynamics.
      Because I-HYPR allows relaxation of the sparsity requirements for the composite
      frame, the iterative reconstruction can enable novel acquisition strategies that
      independently optimize the quality of the composite and temporal resolution of
      the dynamic frames.

PMID- 18058940
TI  - Variable echo time imaging: signal characteristics of 1-M gadobutrol contrast
      agent at 1.5 and 3T.
AB  - Gadobutrol (Gd-Bt; Gadovist(R), Schering AG) is a 1-M Gadolinium (Gd)-based
      contrast agent. Its higher Gd concentration allows for reduction of injection
      volumes in first pass contrast-enhanced MR angiography (CE-MRA) and should
      increase bolus sharpness and image quality. However, ambivalent results were
      reported. In order to explore the performance of 1-M contrast agents such as Gd
      Bt and its dependence on molecular environment and temperature, signal
      characteristics were analyzed for a series of increasing Gd-Bt concentrations for
      different temperature-controlled samples in water and human blood plasma.
      Relaxation times, relaxivities, and signal-concentration curves were assessed for
      several Gd-Bt concentrations in water at 20 degrees C and 37 degrees C and in
      plasma at 37 degrees C for 1.5T and 3T. Gd-Bt concentration influence on signal
      intensity (SI) could be effectively simulated and compared with experimental
      measurements as well as simulations with other contrast agents at realistic in
      vivo concentrations. Particular attention was given to T(2)- and T(*) (2)-induced
      losses at high concentrations, which annihilate benefits from T(1) shortening.
      Based on these findings, variable echo time (VTE) approaches with readout
      bandwidth varying with k-space position were explored in order to enhance the
      signal to noise performance of gradient echo imaging at high contrast agent
      concentrations. Results indicate the potential of VTE for imaging with increased
      SNR at high contrast agent concentrations.

PMID- 18058942
TI  - Increased plasma membrane localization of O-glycosylation-deficient mutant of
      synaptotagmin I in PC12 cells.
AB  - Synaptotagmin I (Syt I) is a Ca2+-binding protein on synaptic vesicles and
      presumably functions as a Ca2+ sensor for neurotransmitter release. Native Syt I
      protein in neuroendocrine PC12 cells undergoes several posttranslational
      modifications, such as O-glycosylation, N-glycosylation, and fatty acylation, and
      the latter two modifications have been shown to be required for the proper
      function of murine Syt I in PC12 cells. However, nothing is known about the
      physiological significance of the O-glycosylation of Syt I in dense-core vesicle
      exocytosis in PC12 cells. In this study, we created an O-glycosylation-deficient
      mutant (named TA = T15A/T16A) and an N-glycosylation-deficient mutant of Syt I
      (named T26A) and investigated their subcellular distribution in Syt I-deficient
      PC12 cells, where other Syt isoforms (e.g., IV and IX) and other membrane
      trafficking proteins (e.g., Rab27A, SNAP-25, syntaxin-1, and VAMP-2) are normally
      expressed. We found that some cells expressing high level of recombinant wild
      type (WT) Syt I protein show mistargeting of Syt I(WT) protein to the plasma
      membrane, whereas most of the cells show normal dense-core vesicle localization
      of Syt I(WT) protein. Similar mistargeting was also observed in cells expressing
      high levels of the Syt I(T26A) and Syt I(TA) mutants, but the mistargeting of the
      Syt I(TA) mutant to the plasma membrane was much more evident than with the Syt
      I(WT) or (T26A) mutant. The results indicate that O-glycosylation, not N
      glycosylation, is partially involved in efficient targeting of Syt I protein to
      dense-core vesicles in PC12 cells.

PMID- 18058941
TI  - Glutathione content as a potential mediator of the vulnerability of cultured
      fetal cortical neurons to ethanol-induced apoptosis.
AB  - Ethanol ingestion during pregnancy elicits damage to the developing brain, some
      of which appears to result from enhanced apoptotic death of neurons. A consistent
      characteristic of this phenomenon is a highly differing sensitivity to ethanol
      within specific neuron populations. One possible explanation for this "selective
      vulnerability" could be cellular variations in glutathione (GSH) homeostasis.
      Prior studies have illustrated that ethanol elicits apoptotic death of neurons in
      the developing brain, that oxidative stress may be an underlying mechanism, and
      that GSH can be neuroprotective. In the present study, both multiphoton
      microscopy and flow cytometry demonstrate a striking heterogeneity in GSH content
      within cortical neuron populations. Ethanol differentially elicits apoptotic
      death and oxidative stress in these neurons. When neuron GSH content is reduced
      by treatment with butathione sulfoxamine, the ethanol-mediated enhancement of
      reactive oxygen species is exacerbated. Sorting of cells into high- and low-GSH
      populations further exemplifies ethanol-mediated oxidative stress whereby
      apoptotic indices are preferentially elevated in the low-GSH population. Western
      blot analysis of the low-GSH subpopulations shows higher ethanol-mediated
      expression of active caspase 3 and 24-kDa PARP-1 fragments compared with the high
      GSH subpopulation. In addition, neuronal content of 4-hydroxynonenal adducts is
      higher in low-GSH neurons in response to ethanol. These studies suggest that GSH
      content is an important predictor of neuronal sensitivity to ethanol-mediated
      oxidative stress and subsequent cell death. The data support the proposition that
      the differences in proapoptotic responses to ethanol within specific neuron
      populations reflect a heterogeneity of neuron GSH content.

PMID- 18058943
TI  - Receptor for advanced glycation end products (RAGE) mediates neuronal
      differentiation and neurite outgrowth.
AB  - The receptor for advanced glycation end products (RAGE) plays a crucial role in
      several disease processes, such as diabetes, inflammation, and neurodegeneration.
      In this article we report multiple roles of RAGE in neuronal differentiation and
      neurite outgrowth. In retinoic-induced P19 embryonic carcinoma stem cells,
      silencing the expression of RAGE by RNA interference (RNAi) blocked
      differentiation of the P19 cells into neuronal cells and enhanced the formation
      of vimentin-positive fibroblast-like cells. RAGE knockdown inhibited retinoic
      acid-induced activation and blocked nuclear translocation of NF-kappaB,
      suggesting RAGE regulates activation of NF-kappaB. RAGE was also shown to be
      involved in survival of P19 cells during retinoic acid differentiation.
      Additionally, knockdown of RAGE strongly inhibited neurite outgrowth in retinoic
      acid-differentiated P19 cells, indicating that RAGE is required for neurite
      outgrowth of differentiated P19 cells. Retinoic acid-treated P19 cells activated
      GTPases, Rac1, and Cdc42. This activation of the GTPases was inhibited in RAGE
      knockdown cells. In primary cerebellar granule neurons, the knockdown of RAGE
      also inhibited neurite outgrowth. In these cells, overexpression of dominant
      negative forms of Rac1 and Cdc42 inhibited neurite outgrowth, whereas
      overexpression of constitutively active forms of Rac1 and Cdc42 in RAGE-deficient
      neurons restored neurite outgrowth, indicating that RAGE mediated neurite
      outgrowth through the Rac1/Cdc42 pathway. This is the first report on the role of
      RAGE in cell lines and primary neurons, as determined by RNAi knockdown.

PMID- 18058944
TI  - Cytoarchitectonics and afferent/efferent reorganization of neurons in layers II
      and III of the lateral entorhinal cortex in the mouse pilocarpine model of
      temporal lobe epilepsy.
AB  - With the mouse pilocarpine model of temporal lobe epilepsy (TLE), we showed a
      progressive loss of both principal cells and calbindin (CB)-, calretinin (CR)-,
      and parvalbumin (PV)-immunopositive interneurons in layers II-III of lateral
      entorhinal cortex (LEnt) from 2 months to 1 year after pilocarpine-induced status
      epilepticus (PISE). In the efferent pathway of LEnt, more Phaseolus vulgaris
      leucoagglutinin (PHA-L)-labelled en passant and terminal boutons with larger
      diameters were shown in the hippocampus and subiculum; in the prefrontal,
      piriform, and perirhinal cortices; and in the amygdaloid complex in experimental
      mice at the two time points compared with the control after iontophoretical
      injection of an anterograde tracer PHA-L into the LEnt. Furthermore, the numbers
      of CB- or CR-immunopositive neurons contacted by PHA-L-labelled en passant and
      terminal boutons decreased in most of these areas at 2 months or 1 year after
      PISE. In the afferent pathway of LEnt, the numbers of retrogradely labelled
      neurons were reduced significantly in the ipsilateral piriform cortex and
      endopiriform nucleus at 2 months and 1 year and in the reuniens thalamic nucleus
      only at 1 year after injection of a retrograde tracer cholera toxin B subunit
      (CTB) into the LEnt. The percentages of the number of CTB and CB or CR double
      labelled neurons of all the retrogradely labelled neurons were also decreased in
      the reunions thalamic nucleus at 1 year after PISE. It is concluded that both
      cytoarchitectonic change and reorganization of afferent and efferent pathways in
      LEnt may be involved in the occurrence of TLE.

PMID- 18058945
TI  - Postnatal developmental regulation of Bcl-2 family proteins in brain
      mitochondria.
AB  - Although it has been long recognized that the relative balance of pro- and
      antiapoptotic Bcl-2 proteins is critical in determining the susceptibility to
      apoptotic death, only a few studies have examined the level of these proteins
      specifically at mitochondria during postnatal brain development. In this study,
      we examined the age-dependent regulation of Bcl-2 family proteins using rat brain
      mitochondria isolated at various postnatal ages and from the adult. The results
      indicate that a general down-regulation of most of the proapoptotic Bcl-2
      proteins present in mitochondria occurs during postnatal brain development. The
      multidomain proapoptotic Bax, Bak, and Bok are all expressed at high levels in
      mitochondria early postnatally but decline in the adult. Multiple BH3-only
      proteins, including direct activators (Bid, Bim, and Puma) and the derepressor
      BH3-only protein Bad, are also present in immature brain mitochondria and are
      down-regulated in the adult brain. Antiapoptotic Bcl-2 family members are
      differentially regulated, with a shift from high Bcl-2 expression in immature
      mitochondria to predominant Bcl-x(L) expression in the adult. These results
      support the concept that developmental differences in upstream regulators of the
      mitochondrial apoptotic pathway are responsible for the increased susceptibility
      of cells in the immature brain to apoptosis following injury.

PMID- 18058947
TI  - Inflammation: a new candidate in modulating adult neurogenesis.
AB  - Any pathological perturbation to the brain provokes a cascade of molecular and
      cellular events, which manifests in the form of microglial activation and release
      of various proinflammatory molecules. This eventually culminates in a profound
      neuroinflammatory reaction that characterizes the brain's response to stress,
      injury, or infection. The inflammatory cascade is an attempt by the system to
      eliminate the challenge imposed on the brain, clear the system of the dead and
      damaged neurons, and rescue the normal functioning of this vital organ. However,
      during the process of microglial activation, the proinflammatory mediators
      released exert certain detrimental effects, and neural stem cells and progenitor
      cells are likely to be affected. Here we review how the proliferation,
      maturation, and migration of the neural stem cells are modulated under such an
      inflammatory condition. The fate of the noncommitted neural stem cells and its
      differentiation potency are often under strict regulation, and these
      proinflammatory mediators seem to disrupt this critical balance and finely tune
      the neurogenesis pattern in the two niches of neurogenesis, the subventricular
      zone and the subgranular zone of the hippocampus. Moreover, the migration ability
      of these stem cells, which is important for localization to the proper site, is
      also affected in a major way by the chemokines released following inflammation.

PMID- 18058948
TI  - Multifaceted roles of sphingosine-1-phosphate: how does this bioactive
      sphingolipid fit with acute neurological injury?
AB  - Sphingosine-1-phosphate (Sph-1-P) is an essential bioactive sphingolipid
      metabolite that has currently become the focus of intense interest. Sph-1-P is
      generated by the enzyme sphingosine kinase (SphK) in response to diverse stimuli,
      including growth factors, cytokines, and G-protein-coupled receptor (GPCR)
      agonists. Its precursor, sphingosine (Sph), is produced from the precursor
      ceramide (Cer) via a ceramidase (CDase) that is released from membrane
      sphingomyelin (SPM) by sphingomyelinases (SMase). Accumulating evidence indicates
      that Sph-1-P is the key regulatory lipid involved in the metabolism of
      sphingolipids and is involved in the control of numerous aspects of cell
      physiology, including mitogenesis, differentiation, migration, and apoptosis.
      These actions of Sph-1-P are mediated by a family of high-affinity S1P receptors,
      named S1P1-5, which are coupled differentially via G(i), G(q), G(12/13), and Rho
      to multiple effector systems, including adenylate cyclase, phospholipases C (PLC)
      and D (PLD), extracellular-signal-regulated kinase, c-Jun N-terminal kinase, p38
      mitogen-activated protein kinase, and nonreceptor tyrosine kinases. In this
      Review, we accumulate available evidence implying that sphingolipid signaling may
      represent a novel neuroprotective target to counteract the pathophysiology of
      acute brain and spinal cord injury in regard to apoptotic cell death mechanisms,
      mitochondrial dysfunction, lipid hydrolysis, and oxidative damage mechanisms.
      Furthermore, we discuss how Sph-1-P agonist approaches might be expected to
      increase the resistance of the central nervous system to injury by promoting
      neurotrophic activity, neurogenesis, and angiogenesis. On the other hand,
      antagonists of certain Sph-1-P-related activity might possess proregenerative
      effects via promotion of neurite growth and inhibition of astrogliotic scarring.

PMID- 18058949
TI  - Myoclonus affecting speech reduced by concurrent handwriting.

PMID- 18058946
TI  - The role of executive function and attention in gait.
AB  - Until recently, gait was generally viewed as a largely automated motor task,
      requiring minimal higher-level cognitive input. Increasing evidence, however,
      links alterations in executive function and attention to gait disturbances. This
      review discusses the role of executive function and attention in healthy walking
      and gait disorders while summarizing the relevant, recent literature. We describe
      the variety of gait disorders that may be associated with different aspects of
      executive function, and discuss the changes occurring in executive function as a
      result of aging and disease as well the potential impact of these changes on
      gait. The attentional demands of gait are often tested using dual tasking
      methodologies. Relevant studies in healthy adults and patients are presented, as
      are the possible mechanisms responsible for the deterioration of gait during dual
      tasking. Lastly, we suggest how assessments of executive function and attention
      could be applied in the clinical setting as part of the process of identifying
      and understanding gait disorders and fall risk.

PMID- 18058950
TI  - Adolescent obsessive compulsive disorder heralding chorea-acanthocytosis.
AB  - We describe one male and one female patient who each developed
      childhood/adolescent obsessive-compulsive disorder as a prelude to the
      development of a typical picture of chorea-acanthocytosis (ChAc). In each
      patient, the caudate nucleus showed dramatic atrophy. The role of the caudate in
      compulsive phenomena, and the predilection for neurological disorders with onset
      in adolescence to present as major mental illness, is discussed. On the basis of
      the current evidence and previous findings, we suggest that ChAc can be
      understood as a disorder whose clinical presentation reflects an interaction
      between the disease process and the individual's neurodevelopmental stage with
      both initial interrupted neurodevelopment, and supervening neurodegeneration.

PMID- 18058951
TI  - Biology and pathobiology of gap junctional channels in hepatocytes.
AB  - The present review provides the state of the art of the current knowledge
      concerning gap junctional channels and their roles in liver functioning. In the
      first part, we summarize some relevant biochemical properties of hepatic gap
      junctional channels, including their structure and regulation. In the second
      part, we discuss the involvement of gap junctional channels in the occurrence of
      liver cell growth, liver cell differentiation, and liver cell death. We further
      exemplify their relevance in hepatic pathophysiology. Finally, a number of
      directions for future liver gap junctional channel research are proposed, and the
      up-regulation of gap junctional channel activity as a novel strategy in (liver)
      cancer therapy is illustrated.

PMID- 18058954
TI  - Introducing negative charges into bis-p-phenylene crown ethers: a study of
      bipyridinium-based [2]pseudorotaxanes and [2]rotaxanes.
AB  - This paper describes novel host-guest systems comprising viologen cations
      (guests) and the derivatives of bis-para-phenylene-34-crown-10 (hosts) with
      anionic groups COO(-) or SO(3)(-). The structure of the resulting charge
      compensated host-guest complexes, their association constants and their
      electrochemical behaviour have been studied. In the solid state, the viologen
      cations thread the negatively charged crown ethers forming electroneutral
      zwitterion-like [2]pseudorotaxane salts; in solution this threaded geometry is
      preserved. The association constants of [2]pseudorotaxane salts incorporating the
      1,1'-diethylviologen moiety in solution are significantly higher than those of
      previously reported analogues. The extrapolated association free energies in non
      aqueous media exceed -40 kJ mol(-1) at 25 degrees C. This significant increase of
      the interaction free energy makes these compounds stable even in aqueous
      solutions. The association constants of [2]pseudorotaxane salts incorporating
      sterically more hindered 1,1'-diethyl-3,3'-dimethylviologen moieties are
      significantly lower. Structurally related [2]rotaxane salts, in which the
      oppositely charged ionic components are mechanically interlocked, have been
      prepared in good yields. It has been shown that [2]rotaxane salts incorporating
      anti-isomers of bisfunctionalised crown ethers are cycloenantiomeric. In both
      [2]pseudorotaxane and [2]rotaxane salts, the electrostatic interactions between
      the viologen moieties and the negatively charged crown ethers lead to very
      significant negative shifts of viologen reduction potentials up to 450 mV. The
      findings of the present study are valuable for the design of nanoscale molecular
      electronic devices.

PMID- 18058952
TI  - Hexamethylene bisacetamide leads to reduced helper virus-free HSV-1 amplicon
      expression titers via suppression of ICP0.
AB  - The herpes simplex virus (HSV)-derived amplicon vector has evolved into a
      promising gene transfer platform for widespread DNA delivery in gene replacement
      strategies and vaccine development given its ease of molecular manipulation,
      large transgene capacity, and transduction efficiencies of numerous cell types in
      vivo. The recent development of helper virus-free packaging methodologies bodes
      well for this vector system in its eventual implementation as a clinically viable
      therapeutic modality. For realization of clinical application, efforts have been
      made to enhance yields and quality of helper-free amplicon stocks. Hexamethylene
      bisacetamide (HMBA), a hybrid polar compound that exhibits stimulatory activity
      of HSV-1 immediate-early gene expression, has been employed as a standard reagent
      in helper virus-free packaging given its purported mode of action on virus gene
      expression kinetics. Unexpectedly, we have found that HMBA exhibits no titer
      enhancing activity; in contrast, the compound enhances the proportion of amplicon
      virions that are non-expressive. Omission of HMBA during vector packaging led to
      a marked reduction in the ratios of vector genome-transducing to transgene
      expressing virions. This effect was neither packaging-cell-specific nor amplicon
      promoter-dependent. Analysis of resultant vector stocks indicated amplicon genome
      replication/concatenation was unaffected, but the level of particle-associated
      ICP0 was reduced in stocks packaged in the presence of HMBA. Inclusion of a co
      transfected, ICP0-expressing plasmid into the packaging process led to
      significant rescue of amplicon expression titers, indicating that regulation of
      ICP0 concentrations is critical for maintenance of the amplicon genome expressive
      state.

PMID- 18058955
TI  - Photostable, amino reactive and water-soluble fluorescent labels based on
      sulfonated rhodamine with a rigidized xanthene fragment.
AB  - Highly water soluble fluorescent dyes were synthesized and transformed into new
      amino reactive fluorescent labels for biological microscopy. To this end,
      rhodamine 8 (prepared from 7-hydroxy-1,2,3,4-tetrahydroquinoline (7) and phthalic
      anhydride in 85 % aq. H(3)PO(4)) was sulfonated with 30 % SO(3) in H(2)SO(4) and
      afforded the water soluble disulfonic acid 3 a (64 %). Amidation of the carboxy
      group in 3 a with 2-(methylamino)ethanol in the presence of O-(7-azabenzotriazol
      1-yl)-N,N,N',N'-tetramethyluroniumPF(6) (-) (HATU) led to alcohol 3 b (66 %),
      which was transformed into the amino reactive mixed carbonate 3 d with di(N
      succinimidyl)carbonate and Et(3)N. Reaction of the carboxy group in 3 a with
      MeNH(CH(2))(2)CO(2)Me and N,N,N',N'-tetramethyl-O-(N-succinimidyl)-uroniumBF(4) (
      ) (TSTU) yielded methyl ester 13. After saponification of the aliphatic carboxy
      group in 13, the compound was converted into NHS-ester 3 e (using HATU and
      Et(3)N). Heating of 7 with trimellitic anhydride in H(3)PO(4) gave a mixture of
      dicarboxylic acids 14 and 15 (1:1). Regioisomer 15 was isolated, sulfonated with
      30 % SO(3) in H(2)SO(4), and disulfonic acid 3 f was used for the synthesis of
      the mono NHS-ester 3 g, in which the sterically unhindered carboxy group was
      selectively activated (with N-hydroxysuccinimide, HATU, and Et(3)N). The
      sulfonated rhodamines 3 b, c and f are soluble in water (up to 0.1 M), have
      excellent photostabilities and large fluorescence quantum yields. Subdiffraction
      resolution images of tubulin filaments of mammalian cells stained with these dyes
      illustrate their applicability as labels for stimulated emission depletion
      microscopy and other fluorescence techniques.

PMID- 18058956
TI  - Directed synthesis of a heterobimetallic complex based on a novel unsymmetric
      double-Schiff-base ligand: preparation, characterization, reactivity and
      structures of hetero- and homobimetallic nickel(II) and zinc(II) complexes.
AB  - A series of bimetallic zinc(II) and nickel(II) complexes based on the novel
      dinucleating unsymmetric double-Schiff-base ligand benzoic acid [1-(3-{[2
      (bispyridin-2-ylmethylamino)ethylimino]methyl}-2-hydroxy-5
      methylphenyl)methylidene]hydrazide (H(2)bpampbh) has been synthesized and
      structurally characterized. The metal centers reside in two entirely different
      binding pockets provided by the ligand H(2)bpampbh, a planar tridentate [ONO] and
      a pentadentate [ON(4)] compartment. The utilized ligand H(2)bpampbh has been
      synthesized by condensation of the single-Schiff-base proligand Hbpahmb with
      benzoic acid hydrazide. The reaction of H(2)bpampbh with two equivalents of
      either zinc(II) or nickel(II) acetate yields the homobimetallic complexes
      [Zn(2)(bpampbh)(mu,eta(1)-OAc)(eta(1)-OAc)] (ZnZn) and [Ni(2)(bpampbh)(mu
      H(2)O)(eta(1)-OAc)(H(2)O)](OAc) (NiNi), respectively. Simultaneous presence of
      one equivalent zinc(II) and one equivalent nickel(II) acetate results in the
      directed formation of the heterobimetallic complex [NiZn(bpampbh)(mu,eta(1)
      OAc)(eta(1)-OAc)] (NiZn) with a selective binding of the nickel ions in the
      pentadentate ligand compartment. In addition, two homobimetallic azide-bridged
      complexes [Ni(2)(bpampbh)(mu,eta(1)-N(3))]ClO(4) (NiNi(N(3))) and
      [Ni(2)(bpampbh)(mu,eta(1)-N(3))(MeOH)(2)](ClO(4))(0.5)(N(3))(0.5)
      (NiNi(N(3))(MeOH)(2)) were synthesized. In all complexes, the metal ions residing
      in the pentadentate compartment adopt a distorted octahedral coordination
      geometry, whereas the metal centers placed in the tridentate compartment vary in
      coordination number and geometry from square-planar (NiNi(N(3))) and square
      pyramidal (ZnZn and NiZn), to octahedral (NiNi and NiNi(N(3))(MeOH)(2)). In the
      case of complex NiNi(N(3)) this leads to a mixed-spin homodinuclear nickel(II)
      complex. All compounds have been characterized by means of mass spectrometry as
      well as IR and UV/Vis spectroscopies. Magnetic susceptibility measurements show
      significant zero-field splitting for the nickel-containing complexes (D=2.9 for
      NiZn, 2.2 for NiNi(N(3)), and 0.8 cm(-1) for NiNi) and additionally a weak
      antiferromagnetic coupling (J=-1.4 cm(-1)) in case of NiNi. Electrochemical
      measurements and photometric titrations reveal a strong Lewis acidity of the
      metal center placed in the tridentate binding compartment towards external donor
      molecules. A significant superoxide dismutase reactivity against superoxide
      radicals was found for complex NiNi.

PMID- 18058957
TI  - Hypervalent silicon versus carbon: ball-in-a-box model.
AB  - Why is silicon hypervalent and carbon not? Or why is [Cl-CH(3)-Cl](-) labile with
      a tendency to localize one of its axial C-Cl bonds and to largely break the other
      one, while the isostructural and isoelectronic [Cl-SiH(3)-Cl](-) forms a stable
      pentavalent species with a delocalized structure featuring two equivalent Si-Cl
      bonds? Various hypotheses have been developed over the years focusing on
      electronic and steric factors. Here, we present the so-called ball-in-a-box
      model, which tackles hypervalence from a new perspective. This model reveals the
      key role of steric factors and provides a simple way of understanding the above
      phenomena in terms of different atom sizes. Our bonding analyses are supported by
      computation experiments in which we probe, among other things, the shape of the
      S(N)2 potential-energy surface of Cl(-) attacking a carbon atom in the series of
      substrates CH(3)Cl, (.)CH(2)Cl, (..)CHCl, and (...)CCl. Our findings for
      ClCH(3)Cl(-) and ClSiH(3)Cl(-) are generalized to other Group 14 central atoms
      (Ge, Sn, and Pb) and axial substituents (F).

PMID- 18058958
TI  - A dicationic organoplatinum(II) complex containing a bridging 2,5-bis-(4
      ethynylphenyl)-[1,3,4]oxadiazole ligand behaves as a phosphorescent gelator for
      organic solvents.
AB  - A dicationic platinum(II) terpyridyl complex, [(tBu3tpy)Pt(OXD)Pt(tBu3tpy)](PF6)2
      (tBu(3)tpy = 4,4',4"-tri-tert-butyl-2,2':6',2"-terpyridyl, OXD = 2,5-bis(4
      ethynylphenyl)[1,3,4]oxadiazole) formed phosphorescent organogels in acetonitrile
      or in a mixture of acetonitrile and alcohol. The structure and properties of
      these emissive gels were analyzed by polarizing optical and confocal laser
      scanning microscopy, and by variable-temperature 1H NMR, UV/Vis, and emission
      spectroscopy. Dry gels were studied by scanning electron microscopy, powder X-ray
      diffraction (PXRD), and small-angle X-ray scattering (SAXS). SEM images of the
      dry gel revealed a network of interwoven nanofibers (diameter 12-60 nm, length >5
      microm). Intermolecular pi-pi interactions between the [(tBu(3)tpy)PtC[triple
      bond]C] moieties could be deduced from the variable 1H NMR spectra. The PXRD and
      SAXS data showed that the assembly of the gelator could be represented by a
      rectangular 2D lattice of 68 A x 14 A. The ability of the complex to gelate a
      number of organic solvents is most likely due to intermolecular pi-pi
      interactions between the [(tBu3tpy)PtC[triple bond]C] moieties.

PMID- 18058959
TI  - Comparison of negative ion electrospray mass spectra measured by seven tandem
      mass analyzers towards library formation.
AB  - A library of negative ion electrospray ionization mass spectra and tandem mass
      spectra (MS/MS) of sulfonated dyes has been developed for fast identification
      purposes. The uniform protocol has been elaborated and applied to the
      measurements of more than 50 anionic dyes. Three collision energies are selected
      in our protocol which ensures that at least one of them provides a suitable ratio
      of product ions to the precursor ion. The robustness is investigated with altered
      values of tuning parameters (e.g. the pressure of the nebulizing gas, the
      temperature and the flow rate of drying gas, and the mobile phase composition).
      The results of the inter-laboratory comparison of product ion mass spectra
      recorded on seven different tandem mass spectrometers (three ion traps, two
      triple quadrupoles and two hybrid quadrupole time of flight instruments) are
      presented for four representative anionic dyes--azo dye Acid Red 118,
      anthraquinone dye Acid Violet 43, triphenylmethane dye Acid Blue 1 and Al(III)
      metal-complex azo dye. The fragmentation patterns are almost identical for all
      tandem mass analyzers, only the ratios of product ions differ somewhat which
      confirms the possibility of spectra transfer among different mass analyzers with
      the goal of library formation.

PMID- 18058960
TI  - Analysis of triacetone triperoxide (TATP) and TATP synthetic intermediates by
      electrospray ionization mass spectrometry.
AB  - The explosive triacetone triperoxide (TATP) has been analyzed by electrospray
      ionization mass spectrometry (ESI-MS) on a linear quadrupole instrument, giving a
      62.5 ng limit of detection in full scan positive ion mode. In the ESI interface
      with no applied fragmentor voltage the m/z 245 [TATP + Na](+) ion was observed
      along with m/z 215 [TATP + Na - C(2)H(6)](+) and 81 [(CH(3))(2)CO + Na](+). When
      TATP was ionized by ESI with an applied fragmentor voltage of 75 V, ions at m/z
      141 [C(4)H(6)O(4) + Na](+) and 172 [C(5)H(9)O(5) + Na](+) were also observed.
      When the precipitates formed in the synthesis of TATP were analyzed before the
      reaction was complete, a new series of ions was observed in which the ions were
      separated by 74 m/z units, with ions occurring at m/z 205, 279, 353, 427, 501,
      575, 649 and 723. The series of evenly spaced ions is accounted for as oligomeric
      acetone carbonyl oxides terminated as hydroperoxides,
      [HOOC(CH(3))(2){OOC(CH(3))(2)}(n)OOH + Na](+) (n = 1, 2 ... 8). The ESI-MS
      spectra for this homologous series of oligoperoxides have previously been
      observed from the ozonolysis of tetramethylethylene at low temperatures.
      Precipitates from the incomplete reaction mixture, under an applied fragmentor
      voltage of 100 V in ESI, produced an additional ion observed at m/z 99
      [C(2)H(4)O(3) + Na](+), and a set of ions separated by 74 m/z units occurring at
      m/z 173, 247, 321, 395, 469 and 543, proposed to correspond to
      [CH(3)CO{OOC(CH(3))(2)}(n)OOH + Na](+) (n = 1,2 ... 5). Support for the assigned
      structures was obtained through the analysis of both protiated and perdeuterated
      TATP samples.

PMID- 18058961
TI  - Laboratory evolved biocatalysts for stereoselective syntheses of substituted
      benzaldehyde cyanohydrins.

PMID- 18058962
TI  - catena-phosphorus cations.
AB  - Recent advances towards a systematic development of catena-phosphorus cations are
      reviewed. The cations represented in this new and developing chapter in
      fundamental phosphorus chemistry complement the series of neutral and anionic
      polyphosphorus compounds.

PMID- 18058963
TI  - Indium-silver- and zinc-silver-mediated barbier-grignard-type alkylation
      reactions of imines by using unactivated alkyl halides in aqueous media.
AB  - In the presence of In or Zn/AgI/InCl(3), an efficient and practical method for
      the Barbier-Grignard-type alkylation reactions of simple imines by using a one
      pot condensation of various aldehydes, amines (including the aliphatic and chiral
      version), and secondary alkyl iodides has been developed. The reaction proceeded
      more efficiently in water than in organic solvents. Without the use of CuI, it
      mainly gave the imine self-reductive coupling product, which was not the
      alkylated product. Good diastereoselectivities (up to 92:8 dr) were obtained when
      L-valine methyl ester was used as the substrate.

PMID- 18058964
TI  - Facile synthesis of gold nanoparticles with narrow size distribution by using
      AuCl or AuBr as the precursor.
AB  - Gold(I) halides, including AuCl and AuBr, were employed for the first time as
      precursors in the synthesis of Au nanoparticles. The synthesis was accomplished
      by dissolving Au(I) halides in chloroform in the presence of alkylamines,
      followed by decomposition at 60 degrees C. The relative low stability of the
      Au(I) halides and there derivatives eliminated the need for a reducing agent,
      which is usually required for Au(III)-based precursors to generate Au
      nanoparticles. Controlled growth of Au nanoparticles with a narrow size
      distribution was achieved when AuCl and oleylamine were used for the synthesis.
      FTIR and mass spectra revealed that a complex, [AuCl(oleylamine)], was formed
      through coordination between oleylamine and AuCl. Thermolysis of the complex in
      chloroform led to the formation of dioleylamine and Au nanoparticles. When
      oleylamine was replaced with octadecylamine, much larger nanoparticles were
      obtained due to the lower stability of [AuCl(octadecylamine)] complex relative to
      [AuCl(oleylamine)]. Au nanoparticles can also be prepared from AuBr through
      thermolysis of the [AuBr(oleylamine)] complex. Due to the oxidative etching
      effect caused by Br(-), the nanoparticles obtained from AuBr exhibited an aspect
      ratio of 1.28, in contrast to 1.0 for the particles made from AuCl. Compared to
      the existing methods for preparing Au nanoparticles through the reduction of
      Au(III) compounds, this new approach based on Au(I) halides offers great
      flexibility in terms of size control.

PMID- 18058966
TI  - Theoretical model for nanoporous carbon supercapacitors.

PMID- 18058965
TI  - A tunable FRET circuit for engineering fluorescent biosensors.

PMID- 18058967
TI  - The next generation of shape-persistant zeolite analogues: covalent organic
      frameworks.

PMID- 18058968
TI  - Predicting drug-resistant mutations of HIV protease.

PMID- 18058969
TI  - A catalytic aldol reaction and condensation through in situ boron "ate" complex
      enolate generation in water.

PMID- 18058970
TI  - Synthesis, characterization, and catalytic activity of a well-defined rhodium
      siloxide complex immobilized on silica.

PMID- 18058971
TI  - Multicolor tuning of (Ln, P)-doped YVO4 nanoparticles by single-wavelength
      excitation.

PMID- 18058972
TI  - A crystalline mesoporous coordination copolymer with high microporosity.

PMID- 18058973
TI  - Ultra-stable peptide scaffolds for protein engineering-synthesis and folding of
      the circular cystine knotted cyclotide cycloviolacin O2.
AB  - The cyclic cystine knot motif, as defined by the cyclotide peptide family, is an
      attractive scaffold for protein engineering. To date, however, the utilisation of
      this scaffold has been limited by the inability to synthesise members of the most
      diverse and biologically active subfamily, the bracelet cyclotides. This study
      describes the synthesis and first direct oxidative folding of a bracelet
      cyclotide-cycloviolacin O2-and thus provides an efficient method for exploring
      the most potent cyclic cystine knot peptides. The linear chain of cycloviolacin
      O2 was assembled by solid-phase Fmoc peptide synthesis and cyclised by thioester
      mediated native chemical ligation, and the inherent difficulties of folding
      bracelet cyclotides were successfully overcome in a single-step reaction. The
      folding pathway was characterised and was found to include predominating fully
      oxidised intermediates that slowly converted to the native peptide structure.

PMID- 18058974
TI  - Reduction of herbivory through wound-activated protein cross-linking by the
      invasive macroalga Caulerpa taxifolia.

PMID- 18058975
TI  - Hypoglycemic activity of Ailanthus excelsa leaves in normal and streptozotocin
      induced diabetic rats.
AB  - The hypoglycemic activity of a 70% methanol extract from the leaves of Ailanthus
      excelsa Roxb. (Simaroubaceae) was studied in normal, transiently hyperglycemic
      and streptozotocin (STZ)-induced diabetic rats. Oral administration of the
      extract at doses of 14, 70 and 350 mg/kg body weight caused no significant
      changes in fasting blood glucose levels of normal rats. In an oral glucose
      tolerance test, the extract produced a significant decrease in glycemia 90 min
      after the glucose pulse. Daily administration of A. excelsa extract for 60 days
      produced a significant hypoglycemic effect in diabetic animals. In addition, this
      treatment improved the altered renal function observed in diabetic control rats.
      This study suggests that Ailanthus leaf extract could be potentially useful for
      post-prandial hyperglycemia treatment.

PMID- 18058976
TI  - Prenatal diagnosis of congenital lipoid adrenal hyperplasia (CLAH) by estriol
      amniotic fluid analysis and molecular genetic testing.
AB  - OBJECTIVE: Congenital lipoid adrenal hyperplasia is an autosomal recessive
      condition due to mutations in Steroidogenic Acute Regulatory Protein (StAR)
      associated with the inability to synthesize all adrenal and gonadal steroids,
      resulting in adrenal insufficiency and failure to develop male genitalia in
      affected 46,XY individuals. We used two independent methods of prenatal diagnosis
      for CLAH. METHOD: CLAH was diagnosed prenatally by measuring amniotic fluid
      estriol, adrenal, and gonadal hormone levels, and by mutation analysis for the
      c.201-202 delCT mutation in StAR. RESULTS: Prenatal testing diagnosed one
      affected and three unaffected fetuses in two families at risk for CLAH.
      CONCLUSION: Prenatal testing for CLAH is effective, and targeted molecular
      genetic analysis should be considered in Palestinian families with a fetus with
      discordant 46,XY karyotype and female genitalia on ultrasound, and low maternal
      serum estriol.

PMID- 18058977
TI  - A 46,XY/46,XX mosaicism diagnosed at amniocentesis: another case report.

PMID- 18058978
TI  - Vitamin K deficiency in hyperemesis gravidarum as a potential cause of fetal
      intracranial hemorrhage and hydrocephalus.

PMID- 18058979
TI  - Rapid protocol for pre-conception genetic diagnosis of single gene mutations by
      first polar body analysis: a possible solution for the Italian patients.

PMID- 18058982
TI  - A direct-write single-step positive etch resist for dip-pen nanolithography.

PMID- 18058985
TI  - Effect of aqueous-ethanol extract from Crocus sativus (saffron) on guinea-pig
      isolated heart.
AB  - In this study, the effects of an aqueous-ethanol extract from Crocus sativus on
      heart rate and contractility were examined. Isolated guinea-pig hearts were
      perfused through the aorta in a Langendorff mode. Heart rate and contractility
      were determined in the presence of four concentrations of the extract (0.1, 0.5,
      1.0 and 5.0 mg%) and diltiazem (0.1, 1, 10 and 100 microm) in perfused heart
      with: (1) ordinary Krebs solution (group 1, n = 9), (2) calcium-free Krebs
      solution (group 2, n = 7). In group 1, three higher concentrations of diltiazem
      (1, 10 and 100 microm), but only the highest (5.0 mg%) and two higher
      concentrations (1.0 and 5.0 mg%) of the extract caused significant reduction in
      heart rate and contractility, respectively (p < 0.05 to p < 0.001). In group 2,
      the highest (100 microm) and two higher concentrations (10 and 100 microm) of
      diltiazem (p < 0.05 to p < 0.01), but only the highest concentration of the
      extract showed significant reductions in the heart rate and contractility (p <
      0.05 to p < 0.01). There were significant negative correlations between
      concentrations of the extract and diltiazem and their effects in both groups (p <
      0.01 to p < 0.001). These results suggested a potent inhibitory effect of aqueous
      ethanol extract from C. sativus on the calcium channel of guinea-pig heart.

PMID- 18058986
TI  - A new antifungal and antiprotozoal depside from the Andean lichen Protousnea
      poeppigii.
AB  - Extracts from the Andean lichens Protousnea poeppigii and Usnea florida displayed
      antimicrobial activity against the pathogenic fungi Microsporum gypseum,
      Trichophyton mentagrophytes and T. rubrum with MIC values between 50 and 100
      microg/mL. From the active extracts, four main metabolites were isolated and
      identified as the new depside, isodivaricatic acid, and the known metabolites 5
      propylresorcinol, divaricatinic acid and usnic acid. Isodivaricatic acid and
      divaricatinic acid presented antifungal effect towards M. gypseum with a MIC of
      50 microg/mL and against T. mentagrophytes and T. rubrum and with MIC values of
      50 and 100 microg/mL, respectively. The new isodivaricatic acid was active
      towards Leishmania amazonensis, Leishmania brasiliensis and Leishmania infantum
      promastigotes with 100% lysis at 100 microg/mL.The activity of the new compound
      decreased on acetylation of the hydroxy groups as well as on methylation of the
      acid function. The structures were elucidated by spectroscopic means. The
      spectroscopic data of isodivaricatic acid are presented here for the first time.

PMID- 18058987
TI  - In vitro and in vivo effects of Ranunculus peltatus subsp. baudotii methanol
      extract on models of eicosanoid production and contact dermatitis.
AB  - Ranunculus (Crowfoot) species are numerous and they are all reputed to be counter
      irritants and are used in several topical conditions. In order to study the
      pharmacological mechanisms of action underlying this popular use, a methanol
      extract of Ranunculus peltatus was tested in vitro in various assays involving
      eicosanoid and human elastase release by intact cells as well as in vivo, with
      models of delayed-type hypersensitivity (DTH) contact dermatitis. The extract
      proved to be a selective inhibitor of the cyclooxygenase-1 pathway, producing the
      total inhibition of 12-(S)-HHTrE release at 200 microg/mL, while leaving both 5
      lipoxygenase and 12-lipoxygenase activities unaffected at the same dose. The n
      hexane, chloroform and ethyl acetate fractions of the crude methanol extract
      inhibited LTB(4) release by intact rat peritoneal neutrophils, but more polar
      fractions were inactive and did not increase the 5-LOX activity as seen
      previously for extracts of other Ranunculus species. In the in vivo models, the
      methanol extract reduced the dinitrofluorobenzene (DNFB)-induced oedema by 40%,
      but failed to inhibit the oedema brought on by oxazolone. The results agree with
      the age-old assertion that Water Crowfoot species can be used as a topical
      antiinflammatory remedy without the prominent irritant action that accompanies
      the application of non-aquatic Ranunculus species.

PMID- 18058988
TI  - Antiviral and immunomodulatory effect of a lyophilized extract of Capparis
      spinosa L. buds.
AB  - Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are
      common human pathogens that in particular cases can also cause severe problems
      especially in immunodeficient patients. The present paper reports the antiviral
      and immunomodulatory properties of a methanolic extract of C. spinosa buds (CAP),
      rich in flavonoids, including several quercetin and kaempferol glycosides. In
      particular we have investigated whether the in vitro exposure of human peripheral
      blood mononuclear cells (PBMCs) to CAP might inhibit the replication of HSV-2 and
      modulate the induction kinetics of IL-12, TNF-alpha IFN-gamma. Our findings have
      shown that CAP treatment interferes with HSV-2 replication in PBMCs inhibiting
      the extracellular virus release upregulating their production of IL-12, IFN-gamma
      and TNF-alpha. One could speculate that CAP may contribute in improving immune
      surveillance of PBMCs toward virus infection by up-regulating expression of
      peculiar proinflammatory cytokines; it should thus be successfully employed for
      treatment of HSV-2 infections in immunocompromised hosts.

PMID- 18058989
TI  - Hypolipidemic activity of Anethum graveolens in rats.
AB  - The aerial parts of Anethum graveolens (dillweed) are used in Iran as a
      hypolipidemic agent. The scientific basis for its use has yet to be established.
      In this study the hypolipidemic activity of dill powder and its essential oil
      (its most important fraction) were evaluated in male Wistar rats (180 +/- 20 g)
      fed a high cholesterol diet. Anethum graveolens essential oil (AGEO) was prepared
      by hydrodistillation and analysed using GC/MS. AGEO had a yield of 2% and GC/MS
      analysis showed that alpha-phellandrene (32%), limonene (28%) and carvone (28%)
      were its major components. Daily oral administration of AGEO to rats at doses of
      45, 90 and 180 mg/kg for 2 weeks significantly and in a dose-dependent manner
      reduced total cholesterol, triglyceride and low density lipoprotein cholesterol
      (LDL-C). AGEO also increased significantly high density lipoprotein cholesterol
      (HDL-C). Anethum graveolens powder when added to the diet of animals showed
      similar effects on serum lipids. It is concluded that Anethum graveolens has
      significant lipid lowering effects and is a promising cardioprotective agent.

PMID- 18058990
TI  - Pharmacological studies on hypotensive, diuretic and vasodilator activities of
      chrysin glucoside from Calycotome villosa in rats.
AB  - The present study was undertaken in normotensive anaesthetized male rats that
      received a continuous perfusion of a chrysin glucoside isolated from the flowers
      and leaves of Calycotome villosa subsp intermedia at a dose of 2.5 mg/kg, or
      furosemide (control diuretic) at a dose of 0.5 mg/kg. Compared with the control
      rats receiving NaCl (0.9%), the urine flow, glomerular filtration and electrolyte
      excretion (Na+, K+) increased significantly in rats treated with chrysin
      glucoside (p < 0.001). A similar effect was observed in the rats perfused with
      furosemide. Intravenous injections of bolus doses (1-3 mg/kg) of the chrysin
      glucoside to anaesthetized rats elicited an immediate and dose-dependent decrease
      in mean arterial blood pressure (MABP). Pretreatment of the rats with the nitric
      oxide synthase inhibitor, l-NOArg (10 mg/kg), reduced partially, but
      significantly (p < 0.01), the maximal decrease in MABP elicited by chrysin
      glucoside. In the rat isolated aorta preparation, chrysin glucoside (10-100
      microm) inhibited in a concentration-dependent manner the noradrenaline (1
      microm) induced contractions (IC(50) = 52 microm). This relaxant activity of
      chrysin glucoside was significantly reduced by incubation of the endothelium
      intact rings with l-NOArg (100 microm), (80 +/- 4.7% vs 48 +/- 5.06% in the
      absence of L-NOArg). In conclusion, these results demonstrate a diuretic and
      hypotensive action of a chrysin glucoside from Calycotome villosa in
      anaesthetized rats and indicating an action on renal function, and an active
      vascular relaxation mediated partially through nitric oxide release.

PMID- 18058991
TI  - Effects of glycyrrhizic acid on cocklebur-induced hepatotoxicity in rat and human
      hepatocytes.
AB  - Herbal medicines are gradually being accepted for their low toxicity and high
      efficacy, but their hepatotoxicity still needs to be recognized. For the multiple
      compounds in herbs, hepatocytes in vitro would be a useful tool for the
      evaluation of herbal hepatotoxicity. This study aimed at cocklebur/atractyloside
      induced hepatotoxicity and the protective effects of glycyrrhizic acid (GA)
      against this toxicity using rat and human hepatocytes in monolayer culture. After
      a 48 h treatment, cocklebur as well as atractyloside induced concentration
      dependent hepatotoxicity according to obvious decreases of cell viability,
      intracellular glutathione (GSH) content and albumin secretion in rat hepatocytes.
      Compared with rat hepatocytes, human hepatocytes seemed to be less sensitive to
      cocklebur-induced hepatotoxicity, indicative of species differences between
      humans and rats. Furthermore, as expected, GA showed significant protective
      effects on cocklebur hepatotoxicity in both human and rat hepatocytes. Overall,
      these results suggested that hepatocytes in vitro, particularly human
      hepatocytes, could be a useful tool for herbal hepatotoxicity screening in vitro.

PMID- 18058992
TI  - Cardioprotective effects of Astragali Radix against isoproterenol-induced
      myocardial injury in rats and its possible mechanism.
AB  - The purpose of the present study was to investigate the effects of the Chinese
      medical herb Astragali Radix on myocardial injury in vivo and its possible
      mechanisms. Myocardial injury in rats was induced by the subcutaneous injection
      of a high dose of isoproterenol for 10 days, and the therapeutic effects of
      Astragali Radix were observed. Cardiac hemodynamics, heart coefficient and marker
      enzymes in serum showed that Astragali Radix prevented isoproterenol-induced
      myocardial damage. Astragali Radix also improved the antioxidant status by
      decreasing the lipid peroxidative product malondialdehyde and increasing the
      activity of the antioxidant enzyme superoxide dismutase. The observed depressions
      in sarcoplasmic reticulum Ca2+-ATPase mRNA and protein expression as well as
      Ser(16)-phosphorylated phospholamban protein expression in isoproterenol-treated
      rats were attenuated by Astragali Radix treatment. Moreover, treatment with
      Astragali Radix showed higher myocardial cAMP content compared with the
      isoproterenol-alone group. These results suggest that the antioxidant property
      and partial prevention of changes in protein and gene expression of cardiac
      sarcoplasmic reticulum Ca2+ regulatory proteins which may be mediated through the
      cAMP pathway could help to explain the beneficial effects of Astragali Radix on
      myocardial injury in vivo.

PMID- 18058993
TI  - Verticinone induces cell cycle arrest and apoptosis in immortalized and malignant
      human oral keratinocytes.
AB  - Although verticinone, a major alkaloid isolated from the bulbus of Fritillaria
      ussuriensis, has been shown to induce differentiation in human leukemia cells,
      the exact mechanism of this action is not completely understood in cancer cells.
      Verticinone was used to conduct growth and apoptosis-related experiments for two
      stages of oral cancer on immortalized human oral keratinocytes (IHOKs) and
      primary oral cancer cells (HN4). The procedures included MTT assay, three
      dimensional (3-D) raft cultures, Western blotting, cell cycle analysis, nuclear
      staining and cytochrome c expression related to the apoptosis signaling pathway.
      Verticinone inhibited the proliferation of immortalized and malignant oral
      keratinocytes in a dose- and time-dependent manner. In 3-D organotypic culture,
      verticinone-treated cells were less mature than the control cells, displaying low
      surface keratinization and decreased epithelial thickness. The major mechanism by
      which verticinone inhibits growth appears to be induced apoptosis and G(0)G(1)
      cell cycle arrest. This finding is supported by the results of the cell cycle
      analysis, FITC-Annexin V staining, DNA fragmentation assay and Hoechst 33258
      staining. Furthermore, the cytosolic level of cytochrome c was increased, while
      the expression of Bcl-2 protein was gradually down-regulated and Bax was up
      regulated, accompanied by caspase-3 activation. The data suggests that
      verticinone may induce apoptosis through a caspase pathway mediated by
      mitochondrial damage in immortalized keratinocytes and oral cancer cells.

PMID- 18058995
TI  - Inferences on the common mean of several log-normal populations: the generalized
      variable approach.
AB  - This paper proposes a novel approach for the confidence interval estimation and
      hypothesis testing of the common mean of several log-normal populations using the
      concept of generalized variable. Simulation studies demonstrate that the proposed
      approach can provide confidence intervals with satisfying coverage probabilities
      and can perform hypothesis testing with satisfying type-I error control even at
      small sample sizes. Overall, it is superior to the large sample approach. The
      proposed method is illustrated using two examples.

PMID- 18058996
TI  - Hemoglobin-E beta thalassemia presenting with recurrent priapism--a rare
      complication.

PMID- 18058994
TI  - Neuropsychiatric symptoms are associated with disability in cognitively impaired
      Latino elderly with and without dementia: results from the Sacramento Area Latino
      study on Aging.
AB  - OBJECTIVE: To examine the relationship between neuropsychiatric symptoms burden
      and disability in cognitively impaired older Latinos. METHODS: Subjects in the
      cross-sectional study were 95 cognitively impaired (both demented and non
      demented) non-institutionalized Latino elderly participating in an
      epidemiological cohort study and their family caregivers. Care recipient
      neuropsychiatric symptoms (Neuropsychiatric Inventory) and level of functional
      impairment (i.e. impairment in activities of daily living and instrumental
      activities of daily living) were assessed through interviews with family
      caregivers. RESULTS: Both NPI total score and NPI depression subscale score were
      significantly associated with disability before and after controlling for
      potential confounding variables. The strength of the association between higher
      neuropsychiatric symptom levels and higher disability was similar for both the
      cognitively impaired not demented and demented groups. CONCLUSIONS:
      Neuropsychiatric symptoms are associated with increased disability in a community
      sample of cognitively impaired Latino elderly. More effective identification and
      treatment of neuropsychiatric symptoms may improve functioning in older Latinos
      and reduce health disparities for this population.

PMID- 18058997
TI  - Clinical application of deferasirox: practical patient management.
AB  - Deferasirox (Exjade, ICL670) is a once-daily, oral iron chelation agent that is
      now widely available for the treatment of transfusional hemosiderosis in adult
      and pediatric patients aged > or =2 years of age. Clinical evaluation has
      established the efficacy and safety of this novel agent in patients with a
      variety of chronic anemias. Deferasirox represents a significant advance in the
      treatment of iron overload, as the availability of an effective oral therapy has
      the potential to relieve many patients from the burden of frequent parenteral
      therapy with the previous reference standard iron chelator, deferoxamine. The
      most common drug-related adverse events seen in the core registration trials were
      gastrointestinal disturbances, rash, mild and nonprogressive increases in serum
      creatinine levels, and elevations in liver enzyme levels. Most events were
      transient, mild-to-moderate in severity, and easily managed without
      discontinuation of treatment. As with any new agent, it is important that
      treating physicians are familiar with the adverse event profile of deferasirox
      and how the associated effects can be readily managed to ensure optimal use of
      this important treatment.

PMID- 18058998
TI  - Smoking in arterial and venous thrombosis: the missing link?

PMID- 18058999
TI  - The erythrocyte mean corpuscular volume is associated with serum levels of
      thyroid stimulating hormone in women.

PMID- 18059000
TI  - Meteorin regulates angiogenesis at the gliovascular interface.
AB  - Brain microvasculature requires a coordinated interaction between endothelial
      cells and astrocytes at the gliovascular interface. However, the role of the
      factors involved in that interaction and expressed by these cells is poorly
      understood. In this study, we demonstrate that Meteorin is highly expressed in
      astrocytes of the brain and retina during the late embryonic and postnatal stages
      of mouse development. Most notably, Meteorin is localized to the astrocyte
      endfeet that surround the blood vessels. To investigate the role of Meteorin in
      perivascular astrocytes, we depleted endogenous levels of Meteorin in cultured
      astrocytes using siRNA, and found that Meteorin attenuates angiogenic activity
      indirectly via astrocyte-derived thrombospondin-1/-2 (TSP-1/-2). Exogenous
      treatment of astrocytes with Meteorin protein also promotes astrocyte expression
      and secretion of TSP-1/-2. The conditioned media from the Meteorin-treated
      astrocytes attenuated angiogenic activity of microvascular endothelial cells.
      This activity was reversed by inhibiting the binding of TSP-1/-2 to its receptor.
      Furthermore, we found that TSP-1/-2 was co-localized with Meteorin in the
      developing brain. Therefore, our data strongly suggests that Meteorin is
      expressed and secreted by perivascular astrocytes and the secreted protein
      upregulates TSP-1/-2 to attenuate angiogenesis in the surrounding endothelial
      cells and to promote vascular maturation.

PMID- 18059002
TI  - Optimization to eliminate the interference of migration isomers for measuring 1-O
      beta-acyl glucuronide without extensive chromatographic separation.
AB  - A highly selected reaction monitoring (SRM) method has been investigated for the
      determination of muraglitazar 1-O-beta-acyl glucuronide in animal and human
      plasma without chromatographic separation of this naturally formed acyl
      glucuronide from its migration isomers. In the ion source or the collision cell,
      glucuronides are often prone to lose the dehydrated glucuronic acid (176 Da) and
      convert back into the parent drug (aglycone). The extent of loss of the
      glucuronide moiety can differ among glucuronides. For the naturally occurring
      muraglitazar 1-O-beta-acyl glucuronide, or its synthetic anomer 1-O-alpha
      glucuronide, the loss of the glucuronide moiety was a major fragment ion. The
      loss of the glucuronide moiety was greater for the 1-O-beta-acyl glucuronide than
      the 1-O-alpha-anomer. In addition, the loss of the glucuronide moiety was
      insignificant (less than 0.01%) with the other glucuronide isomers (2-, 3- or 4
      O, alpha or beta). Given the fact that the 1-O-alpha-anomer was a minor impurity
      in the muraglitazar 1-O-beta-acyl glucuronide reference standard, and not either
      a conversion product of 1-O-beta-acyl glucuronide or endogenously formed, the SRM
      transition corresponding to the loss of the glucuronide moiety was very specific
      for 1-O-beta-acyl glucuronide, and practically free from interference of the
      other isomers under optimized collision-cell conditions. As a result, extensive
      chromatographic separation of 1-O-beta-acyl glucuronide from its migration
      isomers was not required. The use of this specific SRM transition effectively
      reduced the separation time from 12.0 min of a long-column high-performance
      liquid chromatography (HPLC) method to 2.5 min by use of a shorter column. The
      standard curve performance and analysis results of 1-O-beta-acyl glucuronide
      incubation samples showed that the short-column method could produce equivalent
      results to the long-column method but with a 4.5-fold improvement in sample
      throughput. This approach may be useful for other 1-O-beta-acyl glucuronide
      measurements with proper tuning of collision energy. The generation of a
      breakdown curve (abundance vs. collision energy) helps to define whether
      appropriate conditions may be selected for specific MRM transitions.

PMID- 18059001
TI  - Simultaneous lipidomic analysis of three families of bioactive lipid mediators
      leukotrienes, resolvins, protectins and related hydroxy-fatty acids by liquid
      chromatography/electrospray ionisation tandem mass spectrometry.
AB  - Bioactive lipid mediators derived from polyunsaturated fatty acids (PUFA) exhibit
      a range of tissue- and cell-specific activities in many physiological and
      pathological processes. Electrospray ionisation tandem mass spectrometry coupled
      to liquid chromatography (LC/ESI-MS/MS) is a sensitive, versatile analytical
      methodology for the qualitative and quantitative analysis of lipid mediators.
      Here we present an LC/ESI-MS/MS assay for the simultaneous analysis of twenty
      mono- and poly-hydroxy-fatty acid derivatives of linoleic, arachidonic,
      eicosapentaenoic and docosahexaenoic acids. The assay was linear over the
      concentration range 1-100 pg/microL, whilst the limits of detection and
      quantitation were 10-20 and 20-50 pg, respectively. The recovery of the
      extraction methodology varied from 76-122% depending on the metabolite. This
      system is useful for profiling a range of biochemically related potent mediators
      including the newly discovered resolvins and protectins, and their precursor
      hydroxyeicosapentaenoic and hydroxydocosahexaenoic acids, and, consequently,
      advance our understanding of the role of PUFA in health and disease.

PMID- 18059003
TI  - Posaconazole (Noxafil, SCH 56592), a new azole antifungal drug, was a discovery
      based on the isolation and mass spectral characterization of a circulating
      metabolite of an earlier lead (SCH 51048).
AB  - Posaconazole (SCH 56592) is a novel triazole antifungal drug that is marketed in
      Europe and the United States under the trade name 'Noxafil' for prophylaxis
      against invasive fungal infections. SCH 56592 was discovered as a possible active
      metabolite of SCH 51048, an earlier lead. Initial studies have shown that serum
      concentrations determined by a microbiological assay were higher than those
      determined by HPLC from animals dosed with SCH 51048. Subsequently, several
      animals species were dosed with (3)H-SCH 51048 and the serum was analyzed for
      total radioactivity, SCH 51048 concentration and antifungal activity. The
      antifungal activity was higher than that expected based on SCH 51048 serum
      concentrations, confirming the presence of active metabolite(s). Metabolite
      profiling of serum samples at selected time intervals pinpointed the peak that
      was suspected to be the active metabolite. Consequently, (3)H-SCH 51048 was
      administered to a large group of mice, the serum was harvested and the metabolite
      was isolated by extraction and semipreparative HPLC. LC-MS/MS analysis suggested
      that the active metabolite is a secondary alcohol with the hydroxyl group in the
      aliphatic side chain of SCH 51048. All corresponding monohydroxylated
      diastereomeric mixtures were synthesized and characterized. The HPLC retention
      time and LC-MS/MS spectra of the diastereomeric secondary alcohols of SCH 51048
      were similar to those of the isolated active metabolite. Finally, all
      corresponding individual monohydroxylated diasteriomers were synthesized and
      evaluated for in vitro and in vivo antifungal potencies, as well as
      pharmacokinetics. SCH 56592 emerged as the candidate with the best overall
      profile.

PMID- 18059004
TI  - Fragmentation of aromatic sulfonamides in electrospray ionization mass
      spectrometry: elimination of SO(2) via rearrangement.
AB  - Arylsulfonamides are attractive pharmacophores for drug candidates. Fragmentation
      behaviors of selected aromatic sulfonamides were investigated using electrospray
      ionization mass spectrometry in the positive ion mode. Some of the sulfonamides
      afforded unique loss of 64 (loss of SO(2)) ions upon collision-induced
      dissociation followed by intramolecular rearrangements in the gas phase. This
      SO(2) elimination-rearrangement pathway leading to the generation of [M + H -
      SO(2)](+) ions appeared to be susceptible to substitutions on the aromatic (Ar)
      ring that would affect the Ar--sulfur bond strength and the stability of the
      partially positive charge developed at the ipso position upon bond dissociation.
      Electron withdrawing groups such as chlorine attached to the aromatic ring at
      ortho position seem to promote the SO(2) extrusion. Although this fragmentation
      pathway in atmospheric pressure ionization MS is less predictable than in
      electron impact MS, it is a frequently encountered reaction. The absence of this
      fragmentation pathway in some of the arylsulfonamides indicates that other
      factors such as nucleophilicity of the nitrogen may also play a role in the
      process. With respect to the site of attachment of the migrating NR'R'', ipso
      substitution on the aromatic ring is evident since this fragmentation mechanism
      is operative in the fully ortho-substituted arylsulfonamides.

PMID- 18059005
TI  - DMD pseudoexon mutations: splicing efficiency, phenotype, and potential therapy.
AB  - OBJECTIVE: The degenerative muscle diseases Duchenne (DMD) and Becker muscular
      dystrophy result from mutations in the DMD gene, which encodes the dystrophin
      protein. Recent improvements in mutational analysis techniques have resulted in
      the increasing identification of deep intronic point mutations, which alter
      splicing such that intronic sequences are included in the messenger RNA as
      "pseudoexons." We sought to test the hypothesis that the clinical phenotype
      correlates with splicing efficiency of these mutations, and to test the
      feasibility of antisense oligonucleotide (AON)-mediated pseudoexon skipping.
      METHODS: We identified three pseudoexon insertion mutations in dystrophinopathy
      patients, two of whom had tissue available for further analysis. For these two
      out-of-frame pseudoexon mutations (one associated with Becker muscular dystrophy
      and one with DMD), mutation-induced splicing was tested by quantitative reverse
      transcription polymerase chain reaction; pseudoexon skipping was tested using
      AONs composed of 2'-O-methyl-modified bases on a phosphorothioate backbone to
      treat cultured primary myoblasts. RESULTS: Variable amounts of pseudoexon
      inclusion correlates with the severity of the dystrophinopathy phenotype in these
      two patients. AON treatment directed at the pseudoexon results in the expression
      of full-length dystrophin in a DMD myoblast line. INTERPRETATION: Both DMD and
      Becker muscular dystrophy can result from out-of-frame pseudoexons, with the
      difference in phenotype being due to variable efficiency of the newly generated
      splicing signal. AON-mediated pseudoexon skipping therapy is a viable approach to
      these patients and would be predicted to result in increased expression of wild
      type dystrophin protein.

PMID- 18059007
TI  - Measurement of signal-to-noise ratios in sum-of-squares MR images.

PMID- 18059008
TI  - Pregnancy in chronic renal failure: a novel cause of theca lutein cysts at MRI.
AB  - We describe the MRI findings of bilateral ovarian theca lutein cysts in a
      pregnant patient with chronic renal failure. The recognition that pregnancy in
      chronic renal failure may result in theca lutein cysts, presumably due to
      excessive serum beta human chorionic gonadotropins (hCGs) secondary to impaired
      renal excretion, expands the differential diagnosis for this MRI appearance, in
      addition to the usual considerations of gestational trophoblastic disease,
      multiple gestation, and ovarian hyperstimulation.

PMID- 18059009
TI  - Voxel-based analysis of R2* maps in the healthy human brain.
AB  - PURPOSE: To develop a voxel-based analysis of an R2* map of healthy human brain
      that is automatic, reproducible, and realizable in a single examination on a 3T
      MR imager. Such a tool could be useful to measure iron accumulation in
      neurodegenerative diseases. MATERIALS AND METHODS: In all, 18 healthy subjects
      underwent MR imaging at a field strength of 3T: 1) six consecutive T2*-weighted
      gradient-echo volumes were acquired using a segmented echo-planar imaging
      sequence and 2) a conventional dual-echo turbo spin echo sequence was also
      applied to acquire T2-weighted images. Images were realigned and spatial
      correction was performed using a template brain dataset with SPM2. For each
      subject we performed a voxel-by-voxel nonlinear least-squares fitting of the data
      acquired at the six echo times to obtain a monoexponential signal decay curve.
      The reproducibility and sensitivity to age variation were assessed by voxel-based
      analysis. RESULTS: The reproducibility tests in whole brain analysis showed
      little R2* variation. Furthermore, the statistical analysis, performed on each
      brain voxel, revealed a significant positive correlation between age and MR
      values located in regions where a slow and constant age-related iron deposition
      is known. CONCLUSION: Our method, combining data acquisition and data processing,
      demonstrates the feasibility of voxel-based analysis on an R2* map and affords a
      high degree of sensitivity and good reproducibility while maintaining high
      spatial resolution.

PMID- 18059010
TI  - Cutaneous allodynia in the migraine population.
AB  - OBJECTIVE: To develop and validate a questionnaire for assessing cutaneous
      allodynia (CA), and to estimate the prevalence and severity of CA in the migraine
      population. METHODS: Migraineurs (n = 11,388) completed the Allodynia Symptom
      Checklist, assessing the frequency of allodynia symptoms during headache.
      Response options were never (0), rarely (0), less than 50% of the time (1), > or
      = 50% of the time (2), and none (0). We used item response theory to explore how
      well each item discriminated CA. The relations of CA to headache features were
      examined. RESULTS: All 12 questions had excellent item properties. The greatest
      discrimination occurred with CA during "taking a shower" (discrimination = 2.54),
      wearing a necklace (2.39) or ring (2.31), and exposure to heat (2.1) or cold
      (2.0). The factor analysis demonstrated three factors: thermal, mechanical
      static, and mechanical dynamic. Based on the psychometrics, we developed a scale
      distinguishing no CA (scores 0-2), mild (3-5), moderate (6-8), and severe (> or =
      9). The prevalence of allodynia among migraineurs was 63.2%. Severe CA occurred
      in 20.4% of migraineurs. CA was associated with migraine defining features (eg,
      unilateral pain: odds ratio, 2.3; 95% confidence interval, 2.0-2.4; throbbing
      pain: odds ratio, 2.3; 95% confidence interval, 2.1-2.6; nausea: odds ratio, 2.3;
      95% confidence interval, 2.1-2.6), as well as illness duration, attack frequency,
      and disability. INTERPRETATION: The Allodynia Symptom Checklist measures overall
      allodynia and subtypes. CA affects 63% of migraineurs in the population and is
      associated with frequency, severity, disability, and associated symptoms of
      migraine. CA maps onto migraine biology.

PMID- 18059011
TI  - Unintentional parathyroidectomy during total thyroidectomy.
AB  - BACKGROUND: Unintentional parathyroidectomy during thyroidectomy has been
      evaluated in a few studies. Moreover, the impact of the surgeon's experience and
      operative technique has not been evaluated. Our aim was to identify the incidence
      of unintentional parathyroidectomy during total thyroidectomy, its clinical
      consequences, and factors affecting its occurrence. METHODS: We reviewed all
      total thyroidectomies during a 2-year period. Patients were categorized into 2
      groups: those with unintentional parathyroidectomy (parathyroidectomy group) and
      those without unintentional parathyroidectomy (no-parathyroidectomy group).
      RESULTS: Incidental parathyroidectomy occurred in 100 (19.7%) of the 508
      patients. The groups were comparable in age, thyroid weight and pathology,
      operative time, surgeon experience (high/low volume), operative technique (suture
      ligation, LigaSure, or Ultracision), postoperative calcium, and transient
      hypocalcemia. No permanent hypocalcemia occurred. However, 11% of the
      parathyroidectomy group was men compared with 22% of the no-parathyroidectomy
      group (p =.002). CONCLUSIONS: Unintentional parathyroidectomy, although common,
      has no clinical consequences. Unlike surgeon's experience and operative
      technique, patient sex was the only factor affecting its occurrence.

PMID- 18059012
TI  - Accuracy of technetium-99m SPECT-CT hybrid images in predicting the precise
      intraoperative anatomical location of parathyroid adenomas.
AB  - BACKGROUND: This study evaluated the accuracy of single photon emission computed
      tomography (SPECT)-CT imaging for the preoperative localization of parathyroid
      adenomas. METHODS: This study included both a quantitative and qualitative
      accuracy measure. The quantitative measure was the distance between the location
      of the adenoma on the SPECT-CT scan and the location of the adenoma
      intraoperatively. Qualitatively, surgeons were asked whether or not the adenoma
      was in the exact location predicted by the SPECT-CT scan. The time from initial
      incision to identification of the parathyroid was recorded. Patients referred to
      London Health Sciences Centre for a suspected parathyroid adenoma were eligible
      for this study. RESULTS: Twenty-three patients participated in this study.
      Eighteen (78.3%) had a single adenoma, 2 (8.7%) had double adenomas, and 3
      (13.0%) had multiglandular hyperplasia. SPECT-CT correctly detected and localized
      16 of 18 (88.9%) cases of single parathyroid adenomas. The mean distance between
      the location of the adenoma on the SPECT-CT scan and the location of the adenoma
      intraoperatively was 16.3 mm (95% < or = 19.0 mm). For single adenomas, the
      median time from skin incision to identification was 14 minutes (range, 8-40
      minutes). The preoperative detection and localization of a single focus of
      sestamibi uptake yielded a parathyroid adenoma in the specified location in 80.0%
      of cases (95% CI, 97.4-66.5%). CONCLUSIONS: SPECT-CT predicted the intraoperative
      location of a single parathyroid adenoma within 19.0 mm with 95% confidence. The
      correct detection and localization of multiglandular disease remains difficult.

PMID- 18059013
TI  - Lower airway humidification in spontaneously breathing tracheostomized patients:
      comparative study of trachea spray versus heated humidifier.
AB  - BACKGROUND: Our aim was to compare inhalation with molecular water (vaporizing
      humidifier) and particulate water (trachea spray) in spontaneously breathing
      tracheostomized patients. METHODS: We performed a randomized, 2-way crossover
      study and a prospective, comparative, nonblinded study. Tracheal humidity and
      temperature were measured before and after use of a humidifier and spray for 1
      week. RESULTS: After both inhalation and spray, the tracheal temperature and
      total water content increased significantly (study 1). The temperature gradient
      between ambient and tracheal air was significantly higher after spray, but not
      after inhalation (study 2). The water gradient increased nonsignificantly after
      spray and inhalation. The water gradient after inhalation or spray did not differ
      significantly. CONCLUSIONS: Molecular water is not superior to particulate water
      because of temperature and humidity increase after both forms of water delivery.
      Because of its easy use, portability, and moisturizing effect, a trachea spray
      may offer additional options in postoperative tracheostomy care.

PMID- 18059014
TI  - Constitutive regulation of CYP1B1 by the aryl hydrocarbon receptor (AhR) in pre
      malignant and malignant mammary tissue.
AB  - The aryl hydrocarbon receptor (AhR) is a receptor/transcription factor which
      regulates cytochrome P450 (CYP) gene transcription and which is activated by
      environmental carcinogens, some of which are associated with increased breast
      cancer risk. Here, we show that the AhR is over-expressed and constitutively
      active in human and rodent mammary tumors, suggesting its ongoing contribution to
      tumorigenesis regardless of tumor etiology. AhR regulation of CYP1A1 and CYP1B1
      was studied to determine if constitutively active AhR effects the same
      transcriptional outcomes as environmental chemical-activated AhR. Elevated AhR
      and CYP1B1 but not CYP1A1 before tumor formation in a rat model of mammary
      tumorigenesis suggested differential CYP1B1 regulation by a constitutively active
      AhR. This hypothesis was tested with human mammary gland cell lines which hyper
      express AhR and CYP1B1 but which express little or no CYP1A1. CYP1B1 expression
      was diminished by repression of AhR activity or by AhR knockdown, demonstrating
      AhR control of basal CYP1B1 levels. ChIP assays demonstrated constitutive AhR
      binding to both CYP1A1 and CYP1B1 promoters, demonstrating that differential
      CYP1A1 and CYP1B1 regulation by constitutively active AhR does not result from
      different amounts of promoter-bound AhR. While increasing AhR binding to both
      CYP1A1 and CYP1B1, 2,3,7,8-tetrachlorodibenzo-p-dioxin induced CYP1A1 mRNA in
      both a malignant and non-malignant line but increased only CYP1B1 mRNA in the
      malignant line, again demonstrating that the level of promoter binding does not
      necessarily correlate with gene mRNA levels. These studies suggest that
      constitutively active AhR mediates different molecular outcomes than
      environmental chemical-activated AhR, and further implicate the AhR in mammary
      tumorigenesis.

PMID- 18059015
TI  - Beta2-adrenergic receptors expressed on murine chondrocytes stimulate cellular
      growth and inhibit the expression of Indian hedgehog and collagen type X.
AB  - The sympathetic nervous system has been demonstrated to have a role in regulating
      bone remodeling through beta-adrenergic receptors (beta-AR) expressed on
      osteoblasts. Studies using beta(2)-adrenergic receptor agonists in vivo have also
      suggested an effect on endochondral bone development; however, it was not clear
      if this effect was mediated through osteoblasts or chondrocytes. To more
      thoroughly examine the role of beta-AR in chondrocytes we characterized the
      expression and signal transduction systems activated by beta-AR in growth plate
      chondrocytes prepared from ribs of embryonic E18.5 mice. Using RT-PCR and
      immunohistochemistry we found that the chondrocytes expressed only beta(2)-AR.
      The receptors were coupled to stimulation of adenylyl cyclase, phosphorylation of
      the cyclic AMP response element binding protein (CREB) and extracellular signal
      regulated kinase (ERK1/2). Stimulation of ERK1/2 was transient and limited by the
      concomitant stimulation of the mitogen-activated protein kinase phosphatase (MKP
      1). Isoproterenol stimulated the growth of chondrocytes as assessed by increased
      incorporation of [(3)H]-thymidine into the cells. The cellular expression of two
      markers of chondrocyte differentiation, Indian hedgehog, expressed in pre
      hypertrophic cells and collagen type X, expressed in hypertrophic chondrocytes,
      were both significantly inhibited after incubation with isoproterenol.
      Collectively, these findings demonstrate regulation of chondrocytes through
      beta(2)-AR expressed on the cells that stimulate their growth and inhibit their
      differentiation, indicating that the sympathetic nervous system may be an
      important regulator of embryonic cartilage development.

PMID- 18059016
TI  - Daidzein but not other phytoestrogens preserves bone architecture in
      ovariectomized female rats in vivo.
AB  - Ovariectomy of immature female rats, results in significant decrease of
      trabecular bone volume and in cortical bone thickness. Previously, we found that
      estradiol-17beta (E(2)) restored bone structure of ovariectomized (Ovx) female
      rats to values obtained in intact sham-operated female rats. E(2) also
      selectively stimulated creatine kinase (CK) specific activity a hormonal-genomic
      activity marker. In the present study, we compared the effects of E(2) and the
      phytoestrogens: daidzein (D), biochainin A (BA), genistein (G), carboxy
      derivative of BA (cBA), and the SERM raloxifene (Ral) in Ovx, on both
      histological changes of bones and CK, when administered in multiple daily
      injections for 2.5 months. Bone from Ovx rats, showed significant disrupted
      architecture of the growth plate, with fewer proliferative cells and less
      chondroblasts. The metaphysis underneath the growth plate, contained less
      trabeculae but a significant increased number of adipocytes in the bone marrow. D
      like E(2) and Ral but not G, BA, or cBA, restored the morphology of the tibiae,
      similar to that of control sham-operated animals; the bony trabeculeae observed
      in the primary spongiosa was thicker, with almost no adipocytes in bone marrow.
      Ovariectomy resulted also in reduced CK, which in both epiphysis and diaphysis
      was stimulated by all estrogenic compounds tested. In summary, only D stimulated
      skeletal tissues growth and differentiation as effectively as E(2) or Ral,
      suggesting that under our experimental conditions, D is more effective in
      reversing menopausal changes than any of the other isolated phytoestrogens which
      cannot be considered as one entity.

PMID- 18059017
TI  - Mycoplasma infection transforms normal lung cells and induces bone morphogenetic
      protein 2 expression by post-transcriptional mechanisms.
AB  - Bone morphogenetic protein 2 (BMP2) is an essential growth factor and morphogen,
      whose pattern and level of expression profoundly influences development and
      physiology. We present the novel finding that mycoplasma infection induces BMP2
      RNA production in six cell lines of diverse types (mesenchymal, epithelial, and
      myeloid). Mycoplasma infection triggered the expression of mature secreted BMP2
      protein in BEAS-2B cells (immortalized human bronchial epithelial cells), which
      normally do not express BMP2, and further increased BMP2 production in A549 cells
      (lung adenocarcinoma cells). Indeed, mycoplasma is as strong an experimental
      inducer as inflammatory cytokines and retinoic acid. Second, we showed that post
      transcriptional mechanisms including regulation of RNA stability, rather than
      transcriptional mechanisms, contributed to the increased BMP2 expression in
      mycoplasma-infected cells. Furthermore, a novel G-rich oligonucleotide, AS1411
      that binds the post-transcriptional regulator nucleolin induced BMP2 exclusively
      in infected cells. Finally, BMP2 stimulated proliferation in BEAS-2B cells
      transformed by chronic mycoplasma infection, as demonstrated by treatment with
      Noggin, a BMP2 antagonist. These findings have important implications regarding
      the effects of mycoplasma on BMP2-regulated processes, including cell
      proliferation, differentiation, and apoptosis.

PMID- 18059018
TI  - A case report: bone marrow mesenchymal stem cells from a Rett syndrome patient
      are prone to senescence and show a lower degree of apoptosis.
AB  - Rett syndrome (RTT) is one of the most common genetic diseases responsible for a
      progressive disabling neurodevelopmental disorder. Mutations in the MeCP2 gene
      were identified in the great majority of RTT patients. MeCP2 protein binds to
      methylated DNA and produces changes in chromatin structure. This is a key event
      in regulation of gene expression. It has been suggested that MeCP2 might be
      important for neuronal development. Moreover, the frequent occurrence of
      osteoporosis and scoliosis in RTT patients suggests impaired bone formation
      and/or remodeling. Mesenchymal stem cells (MSCs) can differentiate as mesodermal
      cells such as bone, cartilage cells, and adipocytes. MSCs have been shown to
      possess great somatic plasticity; in fact, they can differentiate as neurons and
      astrocytes. We studied RTT patients' MSCs because they are progenitors of
      osteocytes, and it has been suggested that RTT patients' osteogenesis could be
      impaired. Moreover, MSCs might represent a useful model for the study of
      neurogenesis. MSCs from RTT patient showed precocious signs of senescence in a
      comparison with the MSCs of healthy-patient control groups. This was in agreement
      with the reduced gene-expression in the control of stem cell self-renewal and
      upregulation of lineage specific genes, such as those involved in osteogenesis
      and neural development. Control groups enabled us to observe a lower degree of
      apoptosis in RTT patient cells. This means that aberrant stem/progenitor cells,
      instead of being eliminated, can survive and become senescent. Our research
      provides a new insight into RTT syndrome. Senescence phenomena could be involved
      in triggering RTT syndrome-associated diseases.

PMID- 18059019
TI  - Cathelicidin stimulates colonic mucus synthesis by up-regulating MUC1 and MUC2
      expression through a mitogen-activated protein kinase pathway.
AB  - Mucus forms the physical barrier along the gastrointestinal tract. It plays an
      important role to prevent mucosal damage and inflammation. Our animal study
      showed that antibacterial peptide 'cathelicidin' increased mucus thickness and
      prevented inflammation in the colon. In the current study, we examined the direct
      effect and mechanisms by which the peptide increased mucus synthesis in a human
      colonic cell line (HT-29). Human cathelicidin (LL-37) dose-dependently (10-40
      microg/ml) and significantly stimulated mucus synthesis by increasing the D-[6
      (3)H] glucosamine incorporation in the cells. Real-time PCR data showed that
      addition of LL-37 induced more than 50% increase in MUC1 and MUC2 mRNA levels.
      Treatment with MUC1 and MUC2 siRNAs normalized the stimulatory action of LL-37 on
      mucus synthesis. LL-37 also activated the phosphorylation of mitogen-activated
      protein (MAP) kinase in the cells. A specific inhibitor of the MAP kinase
      pathway, U0126, completely blocked the increase of MUC1 and MUC2 expression as
      well as mucus synthesis by LL-37. Taken together, LL-37 can directly stimulate
      mucus synthesis through activation of MUC1 and MUC2 expression and MAP kinase
      pathway in human colonic cells.

PMID- 18059020
TI  - Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the
      natural history of MYH9-related disease.
AB  - MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by
      mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC
      IIA). All patients present from birth with macrothrombocytopenia, but in infancy
      or adult life, some of them develop sensorineural deafness, presenile cataracts,
      and/or progressive nephritis leading to end-stage renal failure. No consistent
      correlations have been identified between the 27 different MYH9 mutations
      identified so far and the variable clinical evolution of the disease. We have
      evaluated 108 consecutive MYH9-RD patients belonging to 50 unrelated pedigrees.
      The risk of noncongenital manifestations associated with different genotypes was
      estimated over time by event-free survival analysis. We demonstrated that all
      subjects with mutations in the motor domain of NMMHC-IIA present with severe
      thrombocytopenia and develop nephritis and deafness before the age of 40 years,
      while those with mutations in the tail domain have a much lower risk of
      noncongenital complications and significantly higher platelet counts. We also
      evaluated the clinical course of patients with mutations in the four most
      frequently affected residues of NMMHC-IIA (responsible for 70% of MYH9-RD cases).
      We concluded that mutations at residue 1933 do not induce kidney damage or
      cataracts and cause deafness only in the elderly, those in position 702 result in
      severe thrombocytopenia and produce nephritis and deafness at a juvenile age,
      while alterations at residue 1424 or 1841 result in intermediate clinical
      pictures. These findings are relevant not only to patients' clinical management
      but also to the elucidation of the pathogenesis of the disease.

PMID- 18059022
TI  - 4-Vinyl-2,6-dimethoxyphenol (canolol) suppresses oxidative stress and gastric
      carcinogenesis in Helicobacter pylori-infected carcinogen-treated Mongolian
      gerbils.
AB  - Oxidative stress is linked to gastric carcinogenesis because of its ability to
      damage DNA. Here we examined antioxidative and anti-inflammatory effects of 4
      vinyl-2,6-dimethoxyphenol (canolol), a recently identified potent antioxidative
      compound obtained from crude canola oil, on Helicobacter (H.) pylori-induced
      gastritis and gastric carcinogenesis using a Mongolian gerbil model. The animals
      were allocated to H. pylori-infection alone (12 weeks) or H.pylori + N-methyl-N
      nitrosourea (MNU) administration (52 weeks). After oral inoculation of H. pylori,
      they were fed for 10 and 44 weeks with or without 0.1% canolol. H. pylori-induced
      gastritis, 5'-bromo-2'-deoxyuridine (BrdU) labeling and scores for cyclooxygenase
      2 (COX-2) and inducible nitric oxide synthase (iNOS) immunohistochemistry were
      attenuated in the canolol-treated groups. Expression of interleukin-1 beta (IL-1
      beta), tumor necrosis factor-alpha (TNF-alpha), COX-2 and iNOS mRNA in the
      gastric mucosa, and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), anti-H. pylori
      IgG and gastrin levels were also significantly lower in canolol-treated groups.
      Furthermore, the incidence of gastric adenocarcinomas was markedly reduced in the
      H. pylori + MNU + canolol-treated group [15.0% (6/40)] compared to the control
      group [39.4% (13/33)] (p < 0.05). These data indicate canolol to be effective for
      suppressing inflammation, gastric epithelial cell proliferation and gastric
      carcinogenesis in H. pylori-infected Mongolian gerbils. Interestingly, the viable
      H. pylori count was not changed by the canolol containing diet. Thus, the data
      point to the level of inflammation because of H. pylori rather than the existence
      of the bacteria as the determining factor. Importantly, canolol appears to
      suppress induction of mRNAs for inflammatory cytokines.

PMID- 18059021
TI  - A case-control study of the association of the polymorphisms and haplotypes of
      DNA ligase I with lung and upper-aerodigestive-tract cancers.
AB  - Tobacco smoking is a major risk factor for lung and upper-aerodigestive-tract
      (UADT) cancers. One possible mechanism for the associations may be through DNA
      damage pathways. DNA Ligase I (LIG1) is a DNA repair gene involved in both the
      nucleotide excision repair (NER) and the base excision repair (BER) pathways. We
      examined the association of 4 LIG1 polymorphisms with lung and UADT cancers, and
      their potential interactions with smoking in a population-based case-control
      study in Los Angeles County. We performed genotyping using the SNPlex method from
      Applied Biosystems. Logistic regression analyses of 551 lung cancer cases, 489
      UADT cancer cases and 948 controls showed the expected associations of tobacco
      smoking with lung and UADT cancers and new associations between the LIG1
      haplotypes and these cancers. For lung cancer, when compared to the most common
      haplotype (rs20581-rs20580-rs20579-rs439132 = T-C-C-A), the adjusted odds ratio
      (OR) is 1.2 (95% confidence limits (CL) = 0.95, 1.5) for the CACA haplotype, 1.4
      (1.0, 1.9) for the CATA haplotype and 1.8 (1.1, 2.8) for the CCCG haplotype,
      after controlling for age, gender, race/ethnicity, education and tobacco smoking.
      We observed weaker associations between the LIG1 haplotypes and UADT cancers. Our
      findings suggest the LIG1 haplotypes may affect the risk of lung and UADT
      cancers.

PMID- 18059024
TI  - SPARC modulates the proliferation of stromal but not melanoma cells unless
      endogenous SPARC expression is downregulated.
AB  - Cell interaction with the extracellular matrix (ECM) has profound influence in
      cancer progression. The secreted protein, acidic and rich in cysteine (SPARC) a
      component of the ECM, impairs the proliferation of different cell types and
      modulates tumor cell aggressive features. This apparent paradox might result
      either from the biochemical properties of the different SPARC sources or from
      differential responses of malignant and stromal cells to SPARC. To test these
      hypotheses, we purified SPARC secreted by melanoma cells (hMel-SPARC) and
      compared its activity with different recombinant SPARC preparations, including a
      new one produced in insect cells. All 5 SPARC species were effective in
      inhibiting bovine aortic endothelial cell proliferation, adhesion and migration.
      We then used the melanoma-derived protein to assess SPARC effect on additional
      cell types. hMel-SPARC greatly impaired the proliferation of both normal and
      transformed human endothelial cells and exerted a moderate biphasic effect on
      human fetal fibroblasts proliferation, irrespective of their endogenous SPARC
      levels. However, SPARC had no effect on the proliferation of several human cancer
      cell lines regardless of their endogenous levels of SPARC expression.
      Importantly, downregulation of SPARC levels in melanoma cells using either an
      antisense RNA or a shRNA against SPARC sensitized them to hMel-SPARC addition in
      proliferation and migration assays, suggesting that malignant cells developed a
      SPARC-resistance mechanism. This was not a general resistance to growth
      suppressing agents, as melanoma cells with restricted SPARC expression were more
      resistant to chemotherapeutic agents. Thus, malignant cells expressing or not
      expressing SPARC developed alternative mechanisms that, in contrary to stromal
      cells, rendered them SPARC-insensitive.

PMID- 18059023
TI  - Aminoflavone induces oxidative DNA damage and reactive oxidative species-mediated
      apoptosis in breast cancer cells.
AB  - Aminoflavone (5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methylchromen-4
      one; AF; NSC 686288), a novel anticancer candidate agent, is undergoing clinical
      evaluation. AF induces DNA-protein cross-links (DPCs), Gamma-H2AX
      phosphorylation, aryl hydrocarbon receptor (AhR) signaling, apoptosis and its own
      metabolism via cytochrome P4501A1 and 1A2 (CYP1A1/1A2) activation in sensitive
      estrogen receptor positive (ER+) MCF7 breast cancer cells. Estrogen receptor
      negative (ER-) breast cancer is typically more aggressive with a poorer
      prognosis. In this investigation, we evaluated the ability of AF to induce
      reactive oxygen species (ROS) formation, oxidative DNA damage and apoptosis in ER
      MDA-MB-468 breast cancer cells. The antioxidant, N-acetyl-L-cysteine (NAC),
      attenuated the cytotoxic effects of AF in MDA-MB-468 cells; an effect is also
      observed in ER+ T47D breast cancer cells. Nonmalignant MCF10A breast epithelial
      cells were resistant to the cytotoxic effects of AF. AF increased intracellular
      ROS, an effect blocked by NAC and the CYP1A1/1A2 inhibitor, alpha-Naphthoflavone
      (alpha-NF). AF induced oxidative DNA damage as evidenced by increased 8-oxo-7,8
      dihydroguanine (8-oxodG) levels and DPC formation in these cells. AF caused S
      phase arrest corresponding to an increase in p21((waf1/cip1)) protein expression.
      AF induced caspase 3, 8 and 9 activation, caspase-dependent apoptotic body
      formation and poly [ADP-ribose] polymerase (PARP) cleavage. Pretreatment with the
      pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-DL-Asp(OMe)-fluoromethylketone
      inhibited apoptosis and partially inhibited ROS formation and oxidative DNA
      damage. Pretreatment with NAC attenuated AF-induced apoptotic body formation and
      caspase 3 activation. These studies suggest AF inhibits the growth of breast
      cancer cells in part, by inducing ROS production, oxidative DNA damage and
      apoptosis and has the potential to treat hormone-independent breast cancer.

PMID- 18059025
TI  - Members of the human papillomavirus type 18 family (alpha-7 species) share a
      common association with adenocarcinoma of the cervix.

PMID- 18059026
TI  - Growth retardation and destruction of experimental squamous cell carcinoma by
      interstitial radioactive wires releasing diffusing alpha-emitting atoms.
AB  - In the present study, we examined the antitumoral effects caused by the release
      of alpha emitting radioisotopes into solid squamous cell carcinoma (SCC) tumors.
      Using a novel method termed DART (Diffusing Alpha-emitters Radiation Therapy), we
      assessed the efficacy of short-lived daughters of (224)Ra releasing alpha
      particles, dispersing in the malignant tissue, to cause tumor growth retardation
      and destruction. It was carried out using specially designed wires loaded with
      (224)Ra activities in the range of 7-42 kBq in a set of experiments performed on
      BALB/c and nude mice bearing metastatic SCC tumors derived from either mouse SQ2
      or human CAL27 cell lines. The insertion of a DART wire to the center of 6-7 mm
      primary tumors, retarded tumor growth, reduced lung metastatic load, prolonged
      life expectancy and in some cases caused tumor eradication. These effects were
      enhanced either when treating smaller tumors or treating identical tumors with 2
      DART wires. Similar experiments on human-derived SCC tumors in nude mice were
      consistent with the outcomes of the murine model. Histological assessments
      revealed the tissue damage pattern, and indicated a role for the tumor
      vasculature in the dispersion of the atoms and the propagation of the damage. Our
      findings indicate that Diffusing Alpha-emitting Radiation Therapy is effective in
      a model system using SCC primary tumors. The in situ destruction of primary solid
      tumors by DART is evidently a necessary step toward curing cancer and might be
      augmented by chemotherapy and other modalities such as immunotherapy or
      antigrowth factors agents.

PMID- 18059028
TI  - Invasive breast cancer cells exhibit increased mobility of the actin-binding
      protein CapG.
AB  - The CapG protein, a Gelsolin-related actin-binding protein, is expressed at
      higher levels in breast cancer, especially in metastasizing breast cancer, than
      in normal breast epithelium. Furthermore, it is known that an increased
      expression of the CapG protein triggers an increase in cell motility. According
      to in vitro experiments, it was supposed that it is the nuclear fraction of the
      protein, which causes the increase in cell motility. Here, we examined the
      dynamical distribution of the CapG protein within the living cell, i.e. the
      import of the CapG protein into the nucleus. The nuclear import kinetics of
      invasive, metastasizing breast cancer cells were compared to the import kinetics
      of non-neoplastic cells similar to normal breast epithelium. FRAP kinetics showed
      a highly significant increase in the recovery of photobleached CapG-eGFP in the
      cancer cells, so that a differentiation of invasive, metastasizing cells and non
      invasive, non-metastasizing cells on the basis of transport processes of the CapG
      protein between the nucleus and the cytoplasm seems to be possible. Comprehension
      of the mobility and compartmentalization of the CapG protein in normal and in
      cancer cells in vivo could constitute a new basis to characterize the
      invasiveness and metastasizing potential of breast cancer.

PMID- 18059027
TI  - Evidence that senescent human prostate epithelial cells enhance tumorigenicity:
      cell fusion as a potential mechanism and inhibition by p16INK4a and hTERT.
AB  - Normal human prostate (NHP) epithelial cells undergo senescence in vitro and in
      vivo but the potential role of senescent NHP cells in prostate tumorigenesis
      remain unclear. Here we show that senescent NHP cells enhance the in vivo
      tumorigenicity of low-tumorigenic LNCaP prostate cancer and low/non-tumorigenic
      subset of cells (called L cells) isolated from multiple bulk-cultured prostate
      (and other) cancer cell lines. Subsequent studies suggest cell-cell fusion as a
      potential mechanism for senescent NHP cell-enhanced tumor development. Using
      fluorescently tagged tumor cells and/or NHP cells, we find that NHP cells, like
      fibroblasts, can undergo fusion with unfractionated tumor cells or the L cells.
      Using 293T-L cells as the model cell system, we verify NHP and 293T-L cell fusion
      by using differential RT-PCR, karyotyping, and gene expression analyses. Further
      experiments demonstrate that senescent NHP cells that have lost progenitor
      markers, accumulated p16INK4a (p16) protein expression, and acquired the AR mRNA
      expression, appear to be the preferential fusion targets. Strikingly, the
      tumorigenicity of the NHP/293T-L hybrid cells was inhibited by exogenous p16 as
      well as hTERT. Chromosomal analyses revealed that hTERT probably inhibited the in
      vivo tumorigenicity by maintaining genomic stability. These results suggest that
      senescent NHP cells, like senescent fibroblasts, may promote tumor development
      and that one of the mechanisms underlying the senescent NHP cell-enhanced
      tumorigenicity could be through cell fusion.

PMID- 18059029
TI  - The impact of tobacco smoking and alcohol drinking on survival of patients with
      non-Hodgkin lymphoma.
AB  - Tobacco smoking and alcohol consumption have not been clearly related to the risk
      of non-Hodgkin lymphoma (NHL), and the impact of these two factors on survival of
      NHL patients has received little attention. Cases were 268 subjects with incident
      histologically-confirmed NHL, admitted as inpatients to the Division of Medical
      Oncology, between 1983 and 2002. These individuals were enrolled as cases in case
      control studies conducted at the same institution over the same period. For all
      patients clinical (histological subtype, major prognostic factors and treatment)
      and epidemiological data (smoking and drinking habits) were available. Survival
      analysis was performed using Kaplan-Meier methods. Hazard ratio (HR) was
      estimated by Cox proportional hazard model. Compared to never smokers, patients
      who smoked >or=20 cigarettes/day had higher risks of death (HR = 1.70, 95%
      confidence interval (CI): 1.06-2.73) and lower survivals at 5 years (60 and 46%,
      respectively). Likewise, patients who drunk >or=4 drinks/day showed 1.69-fold
      higher probability of death (95% CI: 1.04-2.76) in comparison to drinkers of <2
      drinks/day (5-year survival: 47 and 67%, respectively). When combining exposure
      to alcohol and tobacco, no excess of death emerged in light drinkers (<4
      drinks/day), irrespective of their smoking habits, but higher risks of death
      emerged among heavy drinkers. In the present study, heavy tobacco smoking, and
      particularly, heavy alcohol drinking were associated with poor survival in NHL
      patients. Our findings strongly encourage physicians to advice NHL patients to
      stop smoking and diminish alcohol consumption to obtain improvements in the
      course of NHL.

PMID- 18059030
TI  - HPP1-mediated tumor suppression requires activation of STAT1 pathways.
AB  - HPP1 is a recently discovered gene that is epigenetically silenced in a number of
      tumor types, suggesting a potential role as a tumor suppressor. However, whether
      HPP1 has tumor suppressor activity is not clearly known. We have sought to
      investigate the effects of HPP1 on tumor growth and survival and to identify
      signaling pathways that mediate HPP1's mechanism of action. Forced expression of
      HPP1 into HCT116 colon cancer cell lines blocked the ability of HCT116 tumors to
      grown in vivo in nude mice. In cell culture, ectopic expression of HPP1 induces
      apoptosis and potently inhibits soft agar colony formation. HPP1 overexpression
      was also associated with a moderate reduction in in vitro proliferation
      characterized by an accumulation of cells in the G0/G1 phase of the cell cycle.
      Microarray analysis revealed that ectopic expression of HPP1 resulted in a
      dramatic upregulation of STAT1 as well as a large number of associated interferon
      inducible genes. RNA interference-mediated abrogation of STAT1 reversed HPP1's
      antiproliferative effects. We conclude that HPP1 demonstrates tumor suppressive
      and pro-apoptotic activity, both in vitro and in vivo. Coupled with its
      inactivation in a number of tumor types, our data provides evidence to support
      the role of HPP1 as a tumor suppressor gene. Moreover, activation of the STAT1
      pathway likely represents the principal mediator of HPP1's tumor suppressive
      properties.

PMID- 18059031
TI  - Interaction between antioxidant vitamin supplementation and cigarette smoking
      during radiation therapy in relation to long-term effects on recurrence and
      mortality: a randomized trial among head and neck cancer patients.
AB  - There has been concern that the efficacy of radiation therapy may be reduced when
      patients smoke or take antioxidant vitamins during treatment. Cancer prevention
      trials with beta carotene supplements documented adverse effects only among
      smokers. We conducted a randomized trial with alpha tocopherol (400 IU/day) and
      beta carotene (30 mg/day) supplements among 540 head and neck cancer (HNC)
      patients treated by radiation therapy. We examined whether smoking during
      radiation therapy modified the effects of the supplementation on HNC recurrence
      and on mortality. During the follow-up, 119 patients had a HNC recurrence and 179
      died. Cox models were used to test the interaction between smoking and
      supplementation and to estimate the hazard ratios (HR) for HNC recurrence and
      death associated with the supplementation. Cigarette smoking either before or
      after radiation therapy did not modify the effects of the supplementation. In
      contrast, the interactions between supplementation and cigarette smoking during
      radiation therapy were statistically significant for HNC recurrence (p = 0.03),
      all-cause mortality (p = 0.02) and mortality from the initial HNC (p = 0.04).
      Among cigarette smokers, the HR were 2.41 (95% CI: 1.25-4.64) for recurrence,
      2.26 (95% CI: 1.29-3.97) for all-cause mortality and 3.38 (95% CI: 1.11-10.34)
      for HNC mortality. All corresponding HR among nonsmokers were close to 1. These
      results could best be explained by the hypothesis that the combined exposures
      reduced the efficacy of radiation therapy. Particular attention should be devoted
      to prevent patients from both smoking and taking antioxidant supplements during
      radiation therapy.

PMID- 18059032
TI  - Esophageal cancer and body mass index: results from a prospective study of
      220,000 men in China and a meta-analysis of published studies.
AB  - Several epidemiological studies have reported on the association between body
      mass index (BMI) and risk of esophageal cancer, but these were mostly in Western
      populations where many are overweight or obese. There is little direct evidence
      about the relationship in China where the mean BMI is relatively low and the
      disease rate is high. We examined the data from a population-based prospective
      study of 220,000 Chinese men aged 40-79 without a previous history of cancer
      (mean BMI 21.7 kg/m(2)), which included 1,082 esophageal cancer deaths during 10
      years of follow-up. Adjusted hazard ratios for death from esophageal cancer by
      baseline BMI category were calculated using Cox proportional hazards models. Even
      among men with good self-assessed health and BMI >or= 18.5 kg/m(2), there was a
      strong inverse association between BMI and death from esophageal cancer, with
      each 5 kg/m(2) higher BMI associated with 25% (95%CI: 11-36%) lower esophageal
      cancer mortality. This inverse association persisted when analysis was restricted
      to men who had never smoked or when the first 5 years of follow-up were excluded.
      The strength of the relationship was consistent with the pooled estimate for
      squamous cell carcinoma of the esophagus in a meta-analysis of prospective
      studies (31% lower relative risk per 5 kg/m(2) higher BMI; 95% CI: 25-37%), but
      contrasted with that for adenocarcinoma which showed a positive association with
      BMI. Together, these data provide reliable evidence that in many populations low
      BMI is associated with an increased risk of squamous cell carcinoma of the
      esophagus.

PMID- 18059033
TI  - Dickkopf-3 expression is a marker for neuroblastic tumor maturation and is down
      regulated by MYCN.
AB  - Neuroblastoma and ganglioneuroma are neuroblastic tumors originating from the
      developing sympathetic peripheral nervous system. Ganglioneuromas are usually
      benign, while neuroblastomas have a variable prognosis and include very
      aggressive tumors. Examples exist of neuroblastomas regressing to ganglioneuromas
      and ganglioneuromas progressing to neuroblastomas. Little is known of the
      molecular differences between the tumor types. Here we report that Dickkopf-3
      (DKK3), a putative extra cellular inhibitor of the Wnt/beta-catenin pathway,
      showed a strongly differential expression between neuroblastoma and
      ganglioneuroma. Microarray analyses of 109 neuroblastic tumors revealed that DKK3
      is strongly expressed in ganglioneuroma but only weakly in neuroblastoma. Low
      DKK3 expression in neuroblastoma correlated with a poor prognosis. The expression
      of DKK3 in the tumor series and in neuroblastoma cell lines was inversely
      correlated with the expression of the MYCN oncogene. Analysis of 2 neuroblastoma
      cell lines with inducible activity of MYCN showed that DKK3 is down-regulated by
      MYCN. We subsequently generated cell lines with inducible expression of DKK3,
      which revealed an inhibitory effect of DKK3 on proliferation. High DKK3
      expression in the benign ganglioneuromas and down-regulation of DKK3 by MYCN in
      neuroblastoma might contribute to the strongly different clinical behavior of
      both neuroblastic tumor types.

PMID- 18059034
TI  - Frequent epigenetic inactivation of hSRBC in gastric cancer and its implication
      in attenuated p53 response to stresses.
AB  - hSRBC is a putative tumor suppressor located at 11p15.4, at which frequent
      genomic loss has been observed in several human malignancies. To explore the
      candidacy of hSRBC as a suppressor of gastric tumorigenesis, we analyzed the
      expression and mutation status of hSRBC in gastric tissues and cell lines. hSRBC
      transcript was expressed in all normal and benign tumor tissues examined, but
      undetectable or very low in 73% (11/15) cancer cell lines and 41% (46/111)
      primary tumors. Loss or reduction of hSRBC expression was tumor-specific and
      correlated with stage and grade of tumors. While allelic loss or somatic
      mutations of the gene were infrequent, its expression was restored in tumor cells
      by 5-aza-2'-deoxycytidine treatment and aberrant hypermethylation of 23 CpG sites
      in the promoter region showed a tight association with altered expression.
      Transient or stable expression of hSRBC led to a G(1) cell cycle arrest and
      apoptosis of tumor cells, and strongly suppresses colony forming ability and
      xenograft tumor growth. In addition, hSRBC elevated apoptotic sensitivity of
      tumor cells to genotoxic agents, such as 5-FU, etoposide and ultraviolet.
      Interestingly, hSRBC increased the protein stability of p53 and expression of p53
      target genes, such as p21(Waf1), PUMA and NOXA, while hSRBC-mediated cell cycle
      arrest and apoptosis were abolished by blockade of p53 function. Our findings
      suggest that hSRBC is a novel tumor suppressor whose epigenetic inactivation
      contributes to the malignant progression of gastric tumors, in part, through
      attenuated p53 response to stresses.

PMID- 18059036
TI  - Does inhibition of degradation of hypoxia-inducible factor (HIF) alpha always
      lead to activation of HIF? Lessons learnt from the effect of proteasomal
      inhibition on HIF activity.
AB  - At the cellular level hypoxia induces transcriptional response that is mediated
      by the transcription factor hypoxia-inducible factor (HIF). HIF is regulated at
      the level of its alpha subunit by 2-oxoglutarate (2OG)-dependent oxygenases that
      hydroxylate specific prolyl and asparaginyl residues of HIF-alpha, affecting its
      stability and activity, respectively. In the presence of O(2), the alpha subunit
      is degraded in a complex process with several distinct steps. In the first step,
      the degradation process is initiated by prolyl hydroxylases (PHDs). In the second
      step, the von Hippel-Lindau (VHL)/E3 ligase complex recognizes the hydroxylated
      HIF-alpha and mediates its polyubiquitylation by the ubiquitin-conjugating enzyme
      E2. In the third step, the polyubiquitylated HIF-alpha is translocated to the
      proteasome where it is degraded. Degradation of HIF-alpha can be inhibited at any
      of the three levels either by various pharmacological inhibitors or due to
      inactivation of genes whose products regulate the HIF system. The emerging data
      about inactivation of HIF under conditions of proteasomal inhibition prompted us
      to provide an overview contrasting the outcome of inhibition at various stages of
      the degradative pathway for HIF activity.

PMID- 18059037
TI  - World disparities in risk definition and management of retinoblastoma: a report
      from the International Retinoblastoma Staging Working Group.
AB  - Following from the publication of the International Retinoblastoma Staging
      System, an open internet discussion group was created at the www.cure4kids.org
      resource. The results of a survey distributed among participants are discussed.
      Although most patients with retinoblastoma were treated under prospective
      protocols, there was a wide variation in the definition of risk criteria and in
      the criteria for giving adjuvant chemotherapy following enucleation. Definition
      of high-risk histological features and the criteria for use of adjuvant therapy
      will be standardized in future studies. Internet meetings are a valuable
      mechanism for enabling participation from under-resourced countries in the
      development of cooperative studies.

PMID- 18059038
TI  - Atypical facet of Mobius syndrome: association with facioscapulohumeral muscular
      dystrophy.
AB  - We describe a patient with facioscapulohumeral muscular dystrophy (FSHD)
      associated with Mobius syndrome and congenital ophthalmoplegia. This 7-year-old
      girl had profound limitation of extraocular movements since birth, congenital
      facial diplegia, neonatal hypotonia, and progressive limb-girdle weakness. FSHD
      genetic testing revealed a pathogenic haplotype with a D4Z4 repeat of 30 kb. The
      father carries the same allele, although is minimally affected. This unusual case
      expands the genotypic-phenotypic spectrum of FSHD.

PMID- 18059035
TI  - Leptin and leptin receptor genotypes and colon cancer: gene-gene and gene
      lifestyle interactions.
AB  - Leptin may play an important role in colorectal cancer because of its role in
      energy balance, insulin and inflammation. We evaluated the LEP rs2167270 (19 G >
      A) and rs7799039 (-2548 G > A) polymorphisms and the leptin receptor, LEPR
      rs6588147 (located in intron 2), polymorphism with risk of developing colon
      cancer in a study of 1,567 cases and 1,965 controls. We evaluated the effects of
      the polymorphisms with body mass index (BMI), recent use of aspirin/NSAIDs and
      genetic variations in genes related to insulin signaling pathways including
      insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3
      (IGFBP3), and insulin-related substrates 1 and 2 (IRS1, IRS2) and the vitamin D
      receptor (VDR). We observed a slight reduction in colon cancer risk with the AA
      LEP rs2167270 genotype (OR 0.79 95% CI 0.64, 0.98) and although not reaching
      statistical significance, with the combined GG LEP rs2167270 and GG LEPR
      rs6588147 (OR 0.70, 95% CI 0.49, 1.02) genotypes. BMI did not interact with any
      of these polymorphisms to alter colon cancer risk. However, recent aspirin/NSAID
      use significantly interacted with both LEP polymorphisms. Likewise, variants of
      IGF1 and IRS2 interacted with the LEP rs2167270 polymorphism. VDR polymorphisms
      interacted with all LEP and LEPR polymorphisms. These data support an association
      between LEP and colon cancer. They also suggest that the mechanisms linking
      leptin to colon cancer may be independent of energy balance.

PMID- 18059040
TI  - Influence of internal standard charge state on the accuracy of mass measurements
      in orthogonal acceleration time-of-flight mass spectrometers.
AB  - Accuracy of mass measurements performed in orthogonal acceleration time-of-flight
      (oa-TOF) mass spectrometers highly depends on the quality of the signal and the
      internal calibration. The use of two reference compounds which bracket the
      targeted unknown, give rise to ions with sufficient signal-to-noise ratio while
      avoiding detector saturation and produce signals of similar intensity as compared
      to the target is a common requirement which allow a 5 ppm accuracy on a routine
      basis. Ion charge state is demonstrated here to be an additional and particularly
      critical parameter. Using internal references of lower charge state than the
      target ion systematically yielded overestimated data. Errors measured for
      quadruply charged molecules were in the range 16-18 ppm when mass calibrants were
      singly charged ions while accuracy was below 5 ppm when references and target
      ions were in the same charge state. Magnitude of errors was found to increase
      with the difference in charge state. This phenomenon arises from the orthogonal
      acceleration of ions in the TOF analyzer, an interface implemented in all TOF
      mass spectrometers to accommodate continuous beam ionization sources.

PMID- 18059039
TI  - Lifetime course of myasthenia gravis.
AB  - Between 1940 and 2000 a total of 1976 patients with myasthenia gravis (MG) were
      studied. Diagnosis was made by improvement in weakness after anticholinesterase
      medication. The historical developments in diagnosis and treatment of MG are
      reviewed. We analyzed the clinical course of MG as influenced by age, gender,
      thymectomy, thymomectomy, and the presence of antibodies to acetylcholine
      receptors (AChR). The clinical course of MG was significantly influenced by age
      and gender, and these need special attention in managing patients. The most
      severe level of weakness and high mortality occurred during the first 1 to 2
      years of the disease, after which many patients experienced improvement. For
      treating MG patients the usefulness of thymectomy remains to be proven, and novel
      drugs need to be developed to increase the number as well as normal functioning
      of the AChRs and other components of the neuromuscular system.

PMID- 18059041
TI  - Matrix-assisted laser desorption/ionization mechanism study with dihydroxybenzoic
      acid isomers as matrices.
AB  - Desorption and ionization efficiencies of matrix-assisted laser
      desorption/ionization (MALDI) for various biomolecules with different
      dihydroxybenzoic acid isomers were studied. No clear relationships were observed
      between MALDI biomolecule signals vs. gas-phase basicity, proton affinity and
      ionization potential. This indicates the the gas-phase protonation mechanism is
      not adequate to explain the observed results.

PMID- 18059042
TI  - Improved compound-specific delta13C analysis of n-alkanes for application in
      palaeoenvironmental studies.
AB  - We present an optimized method for compound-specific stable carbon isotope
      (delta(13)C) analysis of n-alkanes. For sample preparation, the traditionally
      used Soxhlet extraction was replaced by accelerated solvent extraction (ASE).
      delta(13)C values of individual n-alkanes--measured using gas chromatography
      combustion-isotope ratio mass spectrometry (GC-C-IRMS)--were first drift
      corrected with regularly discharged pure CO(2) pulses as reference gas and,
      secondly, corrected for the amount dependence of the delta(13)C values by co
      analyzing standards with varying analyte concentrations. Finally, the delta(13)C
      values were calibrated against two internal standards. The improved method was
      applied to selected sediment samples from a palaeoenvironmental study in
      subtropical NE Argentina. The measured delta(13)C values of all long-chain n
      alkanes (nC(27), nC(29), nC(31) and nC(33)), representing biomarkers for
      terrestrial plants, correlate significantly with the delta(13)C of bulk organic
      matter (delta(13)C(TOC)). The latter is hence corroborated as a proxy for C3-C4
      vegetation changes. Furthermore, the delta(13)C variations reveal higher
      amplitudes for nC(31) and nC(33) than for nC(27) and nC(29), indicating that the
      former n-alkanes mainly derive from C3 and/or C4 grasses, whereas the latter
      homologues mainly derive from C3 plants (trees and shrubs). Except for the
      lowermost part of the sediment core, the delta(13)C values of the mid-chain
      alkanes nC(23) and nC(25) do not reflect the terrestrial delta(13)C pattern, thus
      indicating that they are probably mainly of lacustrine origin.

PMID- 18059043
TI  - Analysis of phenoxyacetic acid herbicides as biomarkers in human urine using
      liquid chromatography/triple quadrupole mass spectrometry.
AB  - Phenoxyacetic acids are widely used herbicides. The toxicity of phenoxyacetic
      acids is debated, but high-level exposure has been shown to be hepatotoxic as
      well as nephrotoxic in animal studies. An inter-species difference in toxic
      effects has been found, with dogs particularly susceptible. In this study a
      method using liquid chromatography/triple quadrupole mass spectrometry (LC/MS/MS)
      is described for the analysis of 4-chloro-2-methylphenoxyacetic acid (MCPA), and
      its metabolite 4-chloro-2-hydroxymethylphenoxyacetic acid (HMCPA), 2,4
      dichlorophenoxyacetic acid (2,4-D), and 2,4,5-trichlorophenoxyacetic acid (2,4,5
      T) in human urine. The urine samples were treated by acid hydrolysis to degrade
      possible conjugations. The sample preparation was performed using solid-phase
      extraction. Analysis was carried out using selected reaction monitoring (SRM) in
      the negative ion mode. Quantification of the phenoxyacetic acids was performed
      using [(2)H(3)]-labeled MCPA and 2,4-D as internal standards. The method was
      linear in the range 0.05-310 ng/mL urine and has a within-run precision of 2-5%.
      The between-run precision in lower concentration ranges was between 6-15% and
      between 2-8% in higher concentration ranges. The limit of detection was
      determined to 0.05 ng/mL. The metabolites in urine were found to be stable during
      storage at -20 degrees C. To validate the phenoxyacetic acids as biomarkers of
      exposure, the method was applied in a human experimental oral exposure to MCPA,
      2,4-D and 2,4,5-T. Two healthy volunteers received 200 microg of each
      phenoxyacetic acid in a single oral dose followed by urine sampling for 72 h post
      exposure. After exposure, between 90 and 101% of the dose was recovered in the
      urine. In the female subject, 23%, and in the male subject 17%, of MCPA was
      excreted as HMCPA.

PMID- 18059044
TI  - Negative ion dissociation of peptides containing hydroxyl side chains.
AB  - The dissociation of deprotonated peptides containing hydroxyl side chains was
      studied by electrospray ionization coupled with Fourier transform ion cyclotron
      resonance (ESI-FTICR) via sustained off-resonance irradiation collision induced
      dissociation (SORI-CID). Dissociation under post-source decay (PSD) conditions
      was performed by matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF). This work included hexapeptides with one residue of serine,
      threonine, or tyrosine and five inert alanine residues. During SORI-CID and PSD,
      dissociation of [M-H](-) yielded c- and y-ions. Side-chain losses of formaldehyde
      (HCHO) from serine-containing peptides, acetaldehyde (CH(3)CHO) from threonine
      containing peptides, and 4-methylene-2,5-cycohexadienone (C(7)H(6)O) from
      tyrosine-containing peptides were generally observed in the negative ion PSD and
      SORI-CID spectra. Side-chain loss occurs much less from tyrosine-containing
      peptides than from serine- and threonine-containing peptides. This is probably
      due to the bulky side chain of tyrosine, resulting in steric hindrance and poor
      geometry for dissociation reactions. Additionally, a selective cleavage leading
      to the elimination of the C-terminal residue from [M-H](-) was observed from the
      peptides with serine and threonine at the C-terminus. This cleavage does not
      occur in the dissociation of peptides with an amide group at the C-terminus or
      peptides with neutral or basic residues at the C-terminus. It also does not occur
      with tyrosine at the C-terminus. Both the C-terminal carboxylic acid group and
      the hydroxyl side chain of the C-terminal residue must play important roles in
      the mechanism of C-terminal residue loss. A mechanism involving both the C
      terminal carboxylic acid group and a hydroxyl side chain of serine and threonine
      is proposed.

PMID- 18059045
TI  - HPLC analysis and pharmacokinetic study of quercitrin and isoquercitrin in rat
      plasma after administration of Hypericum japonicum thunb. extract.
AB  - A simple HPLC method was developed for determination of quercitrin and
      isoquercitrin in rat plasma. Reversed-phase HPLC was employed for the
      quantitative analysis using kaempferol-3-O-beta-D-glucopyranoside-7-O-alpha-L
      rhamnoside as an internal standard. Following extraction from the plasma samples
      with ethyl acetate-isopropanol (95:5, v/v), these two compounds were successfully
      separated on a Luna C(18) column (250 x 4.6 mm, 5 microm) with isocratic elution
      of acetonitrile-0.5% aqueous acetic acid (17:83, v/v) as the mobile phase. The
      flow-rate was set at 1 mL/min and the eluent was detected at 350 nm for both
      quercitrin and isoquercitrin. The method was linear over the studied ranges of 50
      6000 and 50-5000 ng/mL for quercitrin and isoquercitrin, respectively. The intra-
      and inter-day precisions of the analysis were better than 13.1 and 13.2%,
      respectively. The lower limits of quantitation for quercitrin and isoquercitrin
      in plasma were both of 50 ng/mL. The mean extraction recoveries were 73 and 61%
      for quercitrin and isoquercitrin, respectively. The validated method was
      successfully applied to pharmacokinetic studies of the two analytes in rat plasma
      after the oral administration of Hypericum japonicum thunb. ethanol extract.

PMID- 18059046
TI  - Quantitative determination of domperidone in human plasma by ultraperformance
      liquid chromatography with electrospray ionization tandem mass spectrometry.
AB  - A simple and sensitive liquid chromatography-tandem mass spectrometry method was
      developed and validated for determining domperidone in human plasma. The analyte
      and internal standard (IS; mosapride) were isolated from plasma samples by
      protein precipitation with methanol (containing 0.1% formic acid). The
      chromatographic separation was performed on an Xterra MS C(18) Column (2.1 x 150
      mm, 5.0 microm) with a gradient programme mobile phase consisting of 0.1% formic
      acid and acetonitrile at a flow rate of 0.30 mL/min. The total run time was 4.0
      min. The analyses were carried out by multiple reaction monitoring using the
      parent-to-daughter combinations m/z 426 --> 175 and m/z 422 --> 198 (IS). The
      areas of peaks from the analyte and IS were used for quantification of
      domperidone. The method was validated according to the FDA guidelines on
      bioanalytical method validation. Validation results indicated that the lower
      limit of quantification was 0.2 ng/mL, and the assay exhibited a linear range of
      0.2-60.0 ng/mL and gave a correlation coefficient (r(2)) of 0.999 or better.
      Quality control samples (0.4, 0.8, 15 and 50 ng/mL) in six replicates from three
      different analytical runs demonstrated an intra-assay precision (RSD) 4.43-6.26%,
      an inter-assay precision 5.25-7.45% and an overall accuracy (relative error) of
      <6.92%. The method can be applied to pharmacokinetic and bioequivalence studies
      of domperidone.

PMID- 18059047
TI  - Development and validation of a simple thin layer chromatographic method for the
      analysis of artemisinin in Artemisia annua L. plant extracts.
AB  - Owing to the development of parasite resistance to standard antimalarial
      treatments like chloroquine and sulfadoxine-pyrimethamine, the demand for
      Artemisia annua, a key ingredient for new and highly effective antimalarial
      drugs, is huge. Therefore selective and precise methods to determine the content
      of artemisinin in dry plant material and in raw impure extracts are needed. In
      this work a method is described for the clear separation and extraction of
      artemisinin from other plant components in the Artemisia annua L. plant by thin
      layer chromatography (TLC). To obtain optimal extraction and recovery efficiency,
      several parameters were evaluated, including choice of extraction solvent, TLC
      plate type and sensitivity between UV and visible light. Method validation was
      performed on both the dry plant material and non-purified plant extracts. Toluene
      presented the highest extraction efficiency compared with petroleum ether, hexane
      and methanol. Reversed-phase plates showed more concentrated spots than normal
      phase plates, while the sensitivity of the analysis in UV was comparable to that
      in visible light but less precise. The impure plant extracts were analyzed by
      both TLC and HPLC-UV at 215 nm and both methods met the requirements for
      linearity, selectivity, precision and accuracy. Hence, the proposed TLC method
      can easily be used for both qualitative and quantitative control of the raw plant
      extract in areas where advanced methods are scarce.

PMID- 18059048
TI  - Microbial metabolism of loganin by intestinal bacteria and identification of new
      metabolites in rat.
AB  - Loganin is an important constituent of the traditional Chinese medicine Fructus
      Corni, with several bioactivities. Microbial metabolism of loganin by intestinal
      bacteria was investigated. Two metabolites (log-1 and log-2) were isolated from
      anaerobic culture and their structures were identified by means of their ESI-MS,
      (1)H-NMR, (13)C-NMR and 2D-NMR spectral data. Log-1 was an aglycone of loganin
      and log-2 was proved to be a new compound. In vivo metabolites of loganin were
      detected in rat urine, bile and feces after oral administration of loganin and
      the structures were proved to be identical with that of the microbial metabolites
      log-1 and log-2 by HPLC-PDA analysis and comparison with the reference standards.
      Therefore we can prepare metabolites by anaerobic culture with intestinal
      bacteria.

PMID- 18059049
TI  - A longitudinal study of perfectionism in adolescent onset anorexia nervosa
      restricting type.
AB  - This longitudinal study analyses self-reported perfectionism, eating disorders
      and psychiatric symptoms during recovery from anorexia nervosa (AN). With a
      recovered design, a group of 68 previous patients with AN was studied in two
      follow-up studies, 8 and 16 years after 1st admission to Child and Adolescent
      Psychiatry (CAP). Levels of perfectionism stayed the same while eating disorder
      symptoms and psychiatric symptoms decreased during recovery. Levels of
      perfectionism were inversely related to duration of remission so that individuals
      that had short illness duration had lower levels of perfectionism at both follow
      ups. Patients with initial high levels of perfectionism may be at risk for a long
      illness duration which we recommend clinicians to acknowledge.

PMID- 18059050
TI  - Why (and when) clinicians compel treatment of anorexia nervosa patients.
AB  - OBJECTIVE: This paper addresses the question of the circumstances which lead
      clinicians to use legal coercion in the management of patients with severe
      anorexia nervosa, and explores similarities and differences between such formal
      coercion and other forms of 'strong persuasion' in patient management. METHOD:
      Logistic regression and other statistical analysis was undertaken on 75 first
      admissions for anorexia nervosa from a sample of 117 successive admissions to an
      eating disorder facility in New South Wales, Australia, where an eating disorder
      was the primary diagnosis. Admissions with other primary diagnoses, such as
      bulimia nervosa (25 episodes), and entries with a co-morbid diagnosis (e.g.
      depression or opiate overdose), were discarded, leaving 96 admissions by 75
      individuals. RESULTS: Resort to measures of legal coercion into treatment was
      found to be associated with three main indicators: the patient's past history
      (number of previous admissions); the complexity of their condition (the number of
      other psychiatric co-morbidities); and their current health risk (measured either
      by Body Mass Index (BMI) or the risk of re-feeding syndrome). CONCLUSIONS: Our
      study is consistent with the few earlier studies about indicators for legal
      coercion in anorexia nervosa management, and suggests that clinicians use legal
      coercion very sparingly, distinguishing legal coercion from other forms of close
      clinical management of patients.

PMID- 18059051
TI  - Development and validation of a sensitive LC-MS/MS method with electrospray
      ionization using multiple ions for quantitation of torcetrapib in hamster and dog
      plasma.
AB  - A highly sensitive and specific LC-MS/MS method has been developed and validated
      for the estimation of torcetrapib (TTB) with 100 microL hamster/dog plasma using
      DRL-16126 as an internal standard (IS). The API-4000 Q Trap LC-MS/MS was operated
      under multiple-reaction monitoring mode using the electrospray ionization
      technique. The assay procedure involved extraction of TTB and IS from plasma with
      acetonitrile, which yielded consistent recoveries of 65.73 and 94.01% for TTB and
      79.68 and 90.70% for IS in hamster and dog plasma, respectively. The total
      chromatographic run time was 3.0 min and the elution of TTB and IS occurred at
      approximately 2.25 and 2.20 min, respectively. The resolution of peaks was
      achieved with 0.01 m ammonium acetate:acetonitrile (15:85, v/v) at a flow rate of
      0.40 mL/min on an Inertsil ODS-3 column. The method was proved to be accurate and
      precise at linearity range of 1.00-200 ng/mL with a correlation coefficient (r)
      of > or = 0.993. The method was rugged with 1.00 ng/mL as the lower limit of
      quantitation. TTB was stable in the battery of stability studies. The application
      of the assay to preclinical pharmacokinetic studies confirmed the utility of the
      assay to derive hamster/dog pharmacokinetic parameters.

PMID- 18059052
TI  - A simple and sensitive HPLC method for quantitation of low phenoprolamine
      hydrochloride concentrations in human plasma and its pharmacokinetic application.
AB  - Phenoprolamine hydrochloride is a novel compound that works against a variety of
      types of hypertension. The purpose of this study was to develop a simple and
      sensitive high-performance liquid chromatographic method for quantitation of low
      phenoprolamine hydrochloride concentrations in human plasma and to apply it to
      pharmacokinetic study. The procedure involved extraction of the drug and
      clonidine (internal standard) from the plasma using diethyl ether.
      Chromatographic separations were carried out on a 4.6 x 200 mm Hypersil silica
      column with UV detection at 230 nm. The isocratic mobile phase, 1% ammonium
      acetate (pH 5.4) and methanol (0.3:99.7, v/v), was run at 1 mL/min. Extraction
      recovery was 84% for phenoprolamine hydrochloride at a concentration level of 200
      ng/mL, and 76% for clonidine at 200 ng/mL. The method was linear in the
      concentration range 5-4000 ng/mL with a lower limit of quantitation of 5 ng/mL
      for phenoprolamine hydrochloride. Inter- and intra-day coefficients of variation
      were less than 10%. The validated method was successfully applied to a
      pharmacokinetic study in human after an oral administration of the drug, and the
      pharmacokinetic parameters are presented.

PMID- 18059053
TI  - Determination of forsythiaside in rat plasma by high-performance liquid
      chromatography and its application to pharmacokinetic studies.
AB  - A simple high-performance liquid chromatographic method was developed to study
      the pharmacokinetics of forsythiaside in rat plasma after intravenous
      administration. Hesperidin was used as the internal standard. The drugs were
      separated on a reversed-phase C(18) column and detected at 332 nm. Good linearity
      was achieved in the range of 0.067-26.667 microg/mL. The intra- and inter-assay
      variation coefficients for this analysis were no more than 10.94 and 14.56%,
      respectively. The average recovery for forsythiaside was 87.42% from plasma. The
      analytical sensitivity and accuracy of this assay were adequate for
      characterization of the pharmacokinetics of intravenous administration of
      forsythiaside to rats and the assay has been successfully applied to provide
      pharmacokinetic data. The mean t(1/2Z) was 20.36, 19.40 and 23.62 min for 2, 5
      and 20 mg/kg for forsythiaside after i.v. administration, respectively. The AUC(0
      t) increased linearly from 40.64 to 624.14 microg min/mL after administration of
      the three doses.

PMID- 18059054
TI  - Selective and sensitive determination of bis(7)-tacrine, a high erythrocyte
      binding acetylcholinesterase inhibitor, in rat plasma by high-performance liquid
      chromatography-tandem mass spectrometry.
AB  - The current study aims to develop a specific and sensitive LC-MS/MS method for
      determination of bis(7)-tacrine (B7T) in rat plasma. A 100 microL plasma sample
      was extracted with ethyl acetate. B7T and the internal standard (IS), pimozide,
      in the samples were then analyzed with LC-MS/MS in positive electrospray
      ionization condition. Chromatographic separation of B7T and IS was achieved in a
      C(18) reversed-phase HPLC column (150 x 2.1 mm i.d.) by isocratic elution with a
      mobile phase consisting of 0.05% formic acid in water and acetonitrile (1:1, v/v)
      at a flow rate of 0.35 mL/min. Multiple-reaction monitoring (MRM) mode was
      employed to measure the ion transitions: m/z 247 to 197 for B7T and m/z 462 to
      m/z 328 for IS, respectively. The method was linear over the studied ranges of
      100-5000 and 10-100 ng/mL. The intra-day and inter-day variations of the analysis
      were less than 6.8% with standard errors less than 9.0%. The detection limit of
      B7T in rat plasma was 1 ng/mL. The developed method was successfully applied to
      the pharmacokinetic study of B7T after intravenous administration of 1 mg/kg B7T
      and further proved to be readily utilized for determination of B7T in rat plasma
      samples.

PMID- 18059055
TI  - Relationships between structure, retention and biological activity of some Schiff
      base ligands and their complexes.
AB  - The lipophilicity of a series of Schiff base ligands and their complexes with
      nickel(II) and copper(II) has been determined by reversed-phase thin-layer
      chromatography using binary dioxane-water mobile phase. Chelate ligands were
      prepared by condensation of diamine and the corresponding beta-diketone.
      Copper(II) and nickel(II) complexes with chelate ligands containing ethane-1,2
      diamine or propane-1,2-diamine as the amine part and pentane-2,4-dione and/or 1
      phenylbutane-1,3-dione, pentane-2,4-dione and/or 1,1,1-trifluoropentane-2,4
      dione, or 1,1,1-trifluoropentane-2,4-dione and/or 1-phenylbutane-1,3-dione as the
      beta-diketone part were synthesized. Some of investigated compounds were screened
      for their in vitro antifungal activity against Sacharomyces cerevisiae and
      antibacterial activity against Escherichia coli. Chromatographically obtained
      lipophilicity parameters were correlated both with calculated n-octanol-water
      partition coefficient C log P and antimicrobial activities. Satisfactory
      correlations were obtained. Chromatographic data proved to be reliable parameters
      for describing the lipophilic properties of the investigated compounds.
      Additionally, the principal components analysis was performed on the data
      chromatographically obtained. This statistical method was useful for
      distinguishing compounds and objective comparison of their lipophilicity
      parameters.

PMID- 18059056
TI  - Interaction of glycyrrhetinic acid, furosemide and hydrochlorothiazide with
      bovine serum albumin and their displacement interactions: capillary
      electrophoresis and fluorescence quenching study.
AB  - Licorice is the most widely used crude drug in traditional Chinese medicine.
      Glycyrrhetinic acid (GA) is the metabolite of glycyrrhizic acid, which is the
      main bioactive ingredient of licorice. In this work, capillary electrophoresis
      frontal analysis (CE-FA) was applied to study the binding of bovine serum albumin
      with GA and two diuretics: furosemide (FU) and hydrochlorothiazide (HZ). The
      binding parameters of GA were determined by Scatchard analysis, which showed that
      there are two kinds of binding sites in bovine serum albumin for GA. However, the
      results showed that the CE-FA method was not suitable for the interaction study
      of FU and HZ. Therefore, utracentrifugation-CE was used to probe the binding
      characteristic of these two drugs and the results showed only one kind of binding
      site for them under the studied conditions. Displacement interactions between
      these drugs were also investigated by utracentrifugation-CE method and the
      results showed that GA hardly displaces HZ while it can slightly displace FU and
      FU can slightly displace HZ. For comparison, the binding of these drugs was also
      studied by the fluorescence quenching method and the data were processed by the
      Stern-Volmer quenching equation. Results showed that the binding constants were
      basically consistent for two methods for all drugs studied. The number of binding
      sites on one protein molecule was well consistent for FU and HZ while it was
      quite different for GA.

PMID- 18059057
TI  - Development and validation of a method for the analysis of cafenstrole and its
      metabolite in brown rice grains and rice straw using high-performance liquid
      chromatography.
AB  - The present work reports the extraction and clean-up procedures, as well as the
      chromatographic conditions developed, for the determination of cafenstrole and
      its metabolite (CHM-03) residues in brown rice grains and rice straw using HPLC
      UV detection. The method makes use of an Apollo C(18) column and acetonitrile :
      water : acetic acid as a mobile phase for both cafenstrole and its metabolite in
      rice and rice straw. Using these conditions cafenstrole and its metabolite were
      resolved with a retention time (R(t)) of less than 14 min. The analytes were
      confirmed using positive atmospheric pressure ionization LC-MS with selected ion
      monitoring. The average recoveries of cafenstrole were found to be 87.0-92.5 and
      87.6-88.3%. However, they ranged from 81.5 to 81.6% and from 76.1 to 78.5% for
      cafenstrole metabolite (CHM-03), in rice grains and rice straw, respectively,
      with relative standard deviations ranging from 1.4 to 6.6%. The limits of
      detection (LODs) of both cafenstrole and its metabolite were 0.002 and 0.02 ppm
      and 0.025 and 0.04 ppm, respectively. Field trials with recommended or double the
      recommended dose revealed that the herbicide could safely be recommended for
      application in rice and rice straw as no residues were detected in the harvest
      samples.

PMID- 18059058
TI  - Recent progress in the development of derivatization reagents having a
      benzofurazan structure.
AB  - Chemical derivatization is often used to enhance the detectability of the target
      compounds and to improve the separation efficiency in high-performance liquid
      chromatography (HPLC). In this review, we describe the recent progress in the
      development of derivatization reagents having a benzofurazan structure, namely,
      the fluorogenic reagents, water-soluble reagents, reagents for the analysis of
      peptides and proteins, and reagents for mass spectrometric detection. The
      application of these reagents to bio-samples is also briefly described.

PMID- 18059059
TI  - HPLC assay for determination of amphotericin B in biological samples.
AB  - A fast and selective HPLC method for assaying amphotericin B in biological
      samples was developed and validated. The chromatographic separation was achieved
      in less than 12 min on a reverse-phase C(18) column using an acetonitrile-acetic
      acid-water (52:4.3:43.7, v/v/v) mixture as mobile phase. The flow rate was 1
      mL/min and the effluent was monitored at 406 nm. A linear response over the
      concentration range 0.1-10.0 microg/mL was obtained. Intra-day and inter-day RSDs
      were below 5% for all the sample types. This new HPLC method was applied to assay
      amphotericin B in plasma and several tissue samples such as kidney, liver, spleen
      and bone marrow. Application of this method to pharmacokinetic studies in mice
      and dog is provided.

PMID- 18059060
TI  - Determination of lipophilicity of alpha-(4-phenylpiperazine) derivatives of N
      benzylamides using chromatographic and computational methods.
AB  - This paper describes the evaluation of lipophilicity of alpha-(4
      phenylpiperazine) derivatives of N-benzylamides. We employed reversed-phase thin
      layer chromatography (RP-TLC) and reversed-phase high performance liquid
      chromatography (RP-HPLC) as experimental methods, using mixtures of acetonitrile
      and water as the mobile phases with addition of 0.1%TFA in the HPLC experiments.
      Retention parameters (R(M)) and capacity factors (log k) determined by applying
      these methods were linearly dependent on the acetonitrile concentration and
      enabled us to estimate the relative lipophilicity factors: R(M0) and log k(0).
      These factors were compared with the calculated partition coefficients C log P
      obtained using several software packages. The results indicate that both
      experimental methods (RP-TLC and RP-HPLC) yielded similar results, and these
      methods enable determining the lipophilicity of alpha-(4-phenylpiperazine)
      derivatives of N-benzylamides. Significant correlations were found between log P
      values calculated by Pallas, ALOGPS and C log P Chem3D programs and the
      experimental data.

PMID- 18059061
TI  - Liquid chromatography tandem mass spectrometry method for the quantification of
      rimonabant, a CB1 receptor antagonist, in human plasma.
AB  - A sensitive high-performance liquid chromatography-tandem mass spectrometry
      method was developed and validated for the quantification of rimonabant in human
      plasma. Following liquid-liquid extraction, the analytes were separated using an
      isocratic mobile phase on a reverse-phase column and analyzed by MS/MS in the
      multiple reaction monitoring mode using the respective (M+H)+ ions, m/z 463-363
      for rimonabant and m/z 408-235 for the internal standard. The assay exhibited a
      linear dynamic range of 0.1-100 ng/mL for rimonabant in human plasma. The lower
      limit of quantification was 0.1 ng/mL with a relative standard deviation of less
      than 6%. With dilution integrity up to 10-fold, the upper limit of quantification
      was extendable up to 1000 ng/mL. Acceptable precision and accuracy were obtained
      for concentrations over the standard curve range. A run time of 2.0 min for each
      sample made it possible to analyze more than 250 human plasma samples per day.
      The validated method was successfully used to analyze human plasma samples for
      application in pharmacokinetic studies.

PMID- 18059062
TI  - Stereoselective determination of demethyl- and didemethyl-citalopram in rat
      plasma and brain tissue by liquid chromatography with fluorescence detection
      using precolumn derivatization.
AB  - A rapid and sensitive HPLC enantioselective method with fluorescence detection
      was developed to determine (-)-(R) and (+)-(S) enantiomers of the metabolites of
      citalopram, demethyl- and didemethyl-citalopram in plasma and brain tissue. This
      assay involves pre-column chiral derivatization with (-)-(R)-1-(1-naphthyl)ethyl
      isocyanate followed by separation on a normal-phase silica column. The developed
      liquid-liquid extraction procedure permits quantitative determination of analytes
      with recoveries ranged between 81 and 88% with intra- and inter-day relative
      standard deviations less than 10.5%. Linearity was obtained over the
      concentration range 5-1000 ng/mL and 100-10,000 ng/g for spiked drug-free plasma
      and brain tissue, respectively, with detection limits lower than 2.1 ng/mL and
      42.8 ng/g.

PMID- 18059063
TI  - Twins discordant for fetal skeletal abnormalities: a natural confrontation
      between the two siblings.
AB  - BACKGROUND: Skeletal abnormalities encompass a heterogeneous group of disorders
      characterized by anomalies of cartilage as well as bone growth and development.
      Some are lethal and express early during fetal life, making them amenable to
      prenatal diagnosis. The increasing use of routine ultrasonography (US) during
      pregnancy permits a reliable primary evaluation of the fetal skeleton. However,
      when a skeletal dysplasia is suspected, it is more difficult to establish a
      specific diagnosis. Moreover, detailed ultrasonographic evaluation of the whole
      fetal skeleton may be limited in some circumstances, especially during the third
      trimester due to the fetal position and in the case of multiple pregnancies.
      METHODS: Retrospective study of twin pregnancies complicated with skeletal
      abnormalities. RESULTS: 6 twin pregnancies were reviewed. The prenatal diagnosis
      was correctly made in 66.66% (4/6) with the primary use of combined 2D and 3D-US.
      3D-HCT permits to improve the simultaneous assessment of both fetuses, and is of
      greater value than US in 16.66% (1/6). CONCLUSION: The combined use of 2D or 3D
      US with 3D-HCT permits the best imaging evaluation.

PMID- 18059064
TI  - Simultaneous determination of monomeric and oligomeric alkannins and shikonins by
      high-performance liquid chromatography-diode array detection-mass spectrometry.
AB  - Alkannin and shikonin (A/S) derivatives have been found in the roots of several
      Boraginaceous species and are produced through plant tissue cultures. The chiral
      compounds alkannins and shikonins are potent pharmaceutical substances with a
      wide spectrum of pharmacological activities such as wound healing, antimicrobial,
      anti-inflammatory, anticancer and antioxidant. Although oligomeric A/S
      derivatives have been detected in root extracts and commercial samples their
      detection and determination through high-performance liquid chromatography has
      not been reported. Therefore, in the present study a rapid, simple high
      performance liquid chromatography-diode array detection-mass spectrometry (HPLC
      DAD-MS) method was developed to detect, separate and determine monomeric and
      oligomeric/polymeric derivatives of alkannin/shikonin simultaneously for the
      first time. An optimization of HPLC-DAD parameters was performed. Both
      atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI)
      modes were applied, in order to compare detection of monomeric and oligomeric
      A/S. Additionally, oligomeric A/S constituents in several samples were identified
      and the mode of A/S polymerization was proposed.

PMID- 18059065
TI  - The assessment of absorption of periplocin in situ via intestinal perfusion of
      rats by HPLC.
AB  - Periplocin is an important compound of Cortex Periplocae, which shows poor
      absorption when administered orally. The effective intestinal permeability of
      periplocin was investigated using single-pass intestinal perfusion technique in
      male Wistar rats. SPIP was performed in rat jejunum. The samples of perfusate
      were collected at the designated time points after rat intestinal perfusion and
      analyzed by HPLC. The specificity of this method was demonstrated by the absence
      of interference of the drug peak with the intestinal sac artifacts and the
      components of the KRB solution. Recovery studies, as well as the intra-day and
      inter-day variations, were within statistical limits. This technique was applied
      to the study of the intestinal absorption of periplocin. The determined fraction
      absorbed (F(a)) of periplocin was 0.151 +/- 0.072 (n = 6) at a concentration of 6
      microg/mL; the absorption rate constant (K(a)) was 0.0102 +/- 0.0039/min and the
      effective permeability coefficient (P(eff)) was 0.0021 +/- 0.0012 cm/min. These
      data suggest that periplocin has high permeability and might be absorbed in rat
      intestine.

PMID- 18059066
TI  - Target metabolic profiling analysis of free amino acids in plasma as EOC/TBDMS
      derivatives by GC-SIM-MS.
AB  - Metabolic profiling analysis of free amino acids (AAs) in plasma (20 microL) was
      performed by gas chromatography-mass spectrometry in selected ion monitoring mode
      after ethoxycarbonyl/tert-butyldimethylsilyl derivatives. Characteristic fragment
      ions, including [M - 57](+) ions, permitted sensitive and selective detection of
      most of the AAs in the presence of co-extracted carboxylic acids, including free
      fatty acids, at much higher levels. The overall method was linear (r > or =
      0.9991), reproducible (relative standard deviation = 2.3-8.8%) and accurate
      (relative error = -7.3-7.7%) with detection limits of 0.01-1.9 ng/mL. A total of
      18 AAs, 15 protein AAs and three nonprotein AAs were quantitatively screened in a
      normal human plasma sample. This selective and simple method using a minimal
      sample volume was effective for the quantitation of plasma free AAs.

PMID- 18059067
TI  - Group motivational enhancement therapy as an adjunct to inpatient treatment for
      eating disorders: a preliminary study.
AB  - Difficulties in fostering eating disorder (ED) patients' motivations to overcome
      their illness are widely considered to be a major hurdle in the course of
      successful treatment. However, no previous study has assessed the use of
      interventions specifically designed to target poor motivation amongst patients
      with illnesses that are severe enough to warrant hospitalisation. OBJECTIVE: A
      brief Motivational Enhancement Therapy (MET) group programme for inpatient ED
      sufferers was developed and evaluated. METHOD: Forty two consecutive inpatients
      were sequentially allocated to treatment groups. Twenty three inpatients
      completed a four session MET group programme in addition to routine hospital
      care. A control group of 19 participants completed treatment as usual (TAU).
      RESULTS: Despite an absence of significant differences between the MET and the
      TAU groups on the overall formal outcome measures, there were nevertheless
      differences between the groups. Specifically, the MET groups appeared to foster
      longer term motivation and engagement, and to promote treatment continuation.
      CONCLUSION: The results tentatively suggest that MET could be valuable for the
      treatment of inpatient eating disorder patients and further research is
      warranted.

PMID- 18059068
TI  - Validation of an in vitro model for assessment of androstenedione hepatotoxicity
      using the rat liver cell line clone-9.
AB  - Androstenedione, a naturally occurring steroid hormone, has been used to enhance
      athletic performance. Little is known, however, about its hepatotoxicity. Clone-9
      cells, a non-transformed epithelial cell line that was originally isolated from
      normal liver of a 4-week old Sprague-Dawley rat, were used as an in vitro model
      to assess the hepatotoxic potential of androstenedione. The cultures were treated
      with androstenedione for 24 h at 37 degrees C in 5% CO(2) at concentrations of 0
      100 microg ml(-1). After the treatment period, the cells and the culture
      supernatants were assayed for markers of cytotoxicity which included: release of
      liver enzymes, cell viability, cellular double-stranded DNA content, oxidative
      stress, steatosis, cellular ATP content, caspase-3 activity, the mitochondrial
      permeability transition and induction of cytochrome P450 activity. Significant
      concentration-dependent differences from control were observed in some endpoints
      at medium concentrations of 10 microg ml(-1) and above. These in vitro findings
      were compared with comparable endpoints obtained from an in vivo study of
      androstenedione toxicity in female Sprague-Dawley rats. Of the eight endpoints
      that could be compared between the two studies, only three (lipid accumulation,
      ATP depletion and P450 activity) appeared to be concordant. This suggests that,
      under the experimental conditions used, the clone-9 cells were not a good model
      for androstenedione hepatotoxicity.

PMID- 18059069
TI  - A novel approach to assessing percutaneous VX poisoning in the conscious guinea
      pig.
AB  - Nerve agents like VX (S-2-diisopropylaminoethyl-O-ethyl-methylphosphonothiolate)
      are potent irreversible acetylcholinesterase (AChE) inhibitors. Following
      percutaneous nerve agent exposure there is a slower rate of absorption, later
      onset and longer duration of signs of poisoning. Relatively little is known about
      the physiological effects of percutaneously applied nerve agent in
      unanaesthetised laboratory animals. Heart rate (ECG), brain electrical activity
      (EEG), body temperature, locomotor activity and clinical signs were monitored
      following percutaneous application of VX to conscious guinea-pigs.A fall in heart
      rate (bradycardia) preceded incapacitation following the highest VX dose, and
      occurred in the absence of incapacitation at the lower doses. Following the
      highest dose of VX (0.592 mg kg(-1)) three out of four animals died within 24 h.
      The lower two doses of VX (0.296 and 0.148 mg kg(-1)), produced extended periods
      of bradycardia in the absence of observable signs of poisoning. Bradycardia
      preceded, or occurred in the absence of, a temperature decrease; seizure-like EEG
      changes were not observed at any of the VX doses tested. Acetylcholinesterase
      activity was significantly inhibited in the blood and most brain areas at 48 h.
      There were significant dose-related decreases in body weight at 24 and 48 h
      following VX. This preliminary study suggests that decreased heart rate may be an
      early sign of the toxic effects of VX, whereas temperature and observable
      clinical signs are not good early indicators of percutaneous VX poisoning in this
      animal model. Future studies will use this model to assess the benefit of
      administering medical countermeasures in response to a defined decrease in heart
      rate.

PMID- 18059070
TI  - Personality disorders in 545 patients with eating disorders.
AB  - OBJECTIVE: Previous research on the prevalence of personality disorders in
      patients with eating disorders varies greatly in findings, but a general
      understanding seem to exist that personality disorders are rather common among
      eating-disordered patients. The present investigation is aimed at establishing
      the prevalence of DSM III-R or DSM IV personality disorders in a large population
      seeking treatment for eating disorders. METHOD: Five hundred and forty-five
      patients with DSM IV- eating disorders have been evaluated using the structured
      clinical interview for DSM III-R or IV-Axis II and the eating disorder
      examination. RESULTS: The 29.5% of the population have one or more personality
      disorders according to DSM III-R or DSM IV criteria. Personality disorders, and
      specifically borderline personality disorder, are significantly more common in
      patients with bulimia nervosa. DISCUSSION: The proportion of eating-disordered
      patients with co-morbid personality disorder may not be as large as often found
      in studies. This challenges the understanding of a strong overall connection
      between the two groups of disorder; however, the connection seems to exist in
      subsets of eating disorder samples.

PMID- 18059071
TI  - Prenatal testing for uniparental disomy: indications and clinical relevance.
AB  - This review aims to provide a rational and ethical basis for prenatal testing for
      uniparental disomy (UPD) in cases with abnormal ultrasound findings or numeric
      and/or structural chromosomal aberrations in chorionic villous or amniotic fluid
      samples. The clinical phenotypes of the genomic imprinting-associated paternal
      UPD 6 (transient neonatal diabetes mellitus), maternal UPD 7 (Silver-Russell
      syndrome), paternal UPD 11p (Beckwith-Wiedemann syndrome), maternal UPD 14
      (precocious puberty, short stature and highly variable developmental delay),
      paternal UPD 14 (polyhydramnios and a bell-shaped thorax), maternal UPD 15
      (Prader-Willi syndrome), paternal UPD 15 (Angelman syndrome), maternal UPD 16 and
      UPD 20, as well as the diagnostic options, are summarized. In addition, the
      clinical impact of UPD testing and its relevance in various prenatal diagnostic
      situations are discussed. As a general rule, prenatal UPD testing, following
      genetic counseling, is justified if paternal UPD 14, maternal UPD 15 or paternal
      UPD 15 are suspected. In contrast, considering the mild phenotypes of paternal
      UPD 6 and maternal UPD 7, prenatal UPD testing is questionable. Because of the
      highly variable phenotype for paternal UPD 11p, maternal UPD 14 and maternal UPD
      16, prenatal testing should be discussed critically on an individual basis. For
      all other chromosomes, prenatal UPD testing is purely academic and should
      therefore not be performed on a routine basis, particularly because a positive
      result might confuse the parents more than it actually helps them.

PMID- 18059072
TI  - Matrix metalloproteinases 2 and 9 in central nervous system and their
      modification after vanadium inhalation.
AB  - Vanadium (V) derivatives are well-known environmental pollutants and its toxicity
      has been related with oxidative stress. Toxicity after vanadium inhalation on the
      substantia nigra, corpus striatum, hippocampus and ependymal epithelium was
      reported previously. The purpose of this study was to analyse the role of matrix
      metalloproteinases 2 (MMP-2) and 9 (MMP-9) in the changes observed in brain
      tissue after chronic V inhalation. Mice were exposed to vaporized, vanadium
      pentoxide 0.02 m in deionized water for 1 h twice a week, and killed at 1 h, 1, 2
      and 4 weeks after exposure. The brain was removed and the olfactory bulb,
      prefrontal cortex, striatum and hippocampus were dissected and the MMP content
      was obtained by zymography. The results showed that MMP-9 increased in all the
      structures at the end of the exposure, although in the hippocampus this increment
      was evident after 1 week of exposure. When MMP-2 was analysed in the olfactory
      bulb and prefrontal cortex it remained unchanged throughout the whole exposure,
      while in the hippocampus it increased at week 4, while in the striatum MMP-2
      increased from the second week only, through the whole experiment. These results
      demonstrate that V increased MMPs in different structures of the CNS and this
      change might be associated with the previously reported modifications, such as
      dendritic spine loss and neuronal cell death. The modifications in MMPs could be
      related with blood-brain barrier (BBB) disruption which was reported previously.
      Oxidative stress might also be involved in the activation of these gelatinases as
      part of the different mechanisms which take place in V toxicity in the CNS.

PMID- 18059073
TI  - The Portuguese short form of the Eating Attitudes Test-40.
AB  - To develop a Portuguese short form, the Eating Attitudes Test-40 (EAT-40) was
      administered to a community sample of 922 female students and to a clinical
      sample of 63 females suffering from an eating disorder. With the EAT responses of
      the community sample a factor analysis was performed and items with factor
      loadings > or = 0.30 were selected. Internal consistency was computed for both
      the instrument and the factors. To study the discriminant capacity the proportion
      of symptomatic answers and the mean scores were compared between the clinical (N
      = 63) and control (N = 63) samples. Three factors were extracted: Drive for
      Thinness (14 items, alpha = .839), Bulimic Behaviours (8 items, alpha = .670),
      Social Pressure to Eat (3 items, alpha = .758). The short form is composed of 25
      items and shows good internal consistency = 0.839. Symptomatic answers for all
      items (except one) and total mean scores were significantly higher (p < .001) in
      the clinical sample than in community sample.

PMID- 18059074
TI  - The inpatient management of physical activity in young people with anorexia
      nervosa.
AB  - This study investigates the management of physical activity in young inpatients
      with anorexia nervosa. Through telephone interviews and postal surveys inpatient
      units across the UK were asked about written documents regarding physical
      activity management, how they viewed healthy exercise, how they assessed physical
      fitness to engage in activity, the management approaches taken, provision of
      education and support around this issue and range of activities provided. Results
      indicated that a variety of approaches were taken, with little consensus between
      units, although the majority of approaches did involve some form of restriction,
      frequently determined by weight criteria. There were few substantial written
      documents to guide practice and a range of interpretations of healthy exercise.
      The findings are discussed and suggestions made for research to explore this area
      further and to inform the development of effective interventions.

PMID- 18059075
TI  - A caution regarding standardization of power Doppler to measure perfusion in
      placental tissue.

PMID- 18059077
TI  - Correlation between anal sphincter defects and anal incontinence following
      obstetric sphincter tears: assessment using scoring systems for sonographic
      classification of defects.
AB  - OBJECTIVE: To determine if there is a correlation between the sonographic extent
      of anal sphincter defects revealed by three-dimensional endoanal sonography
      (EAUS) and the degree of anal incontinence following primary repair of obstetric
      sphincter tears. METHODS: This was a follow-up study of women who had suffered
      anal sphincter tearing during vaginal delivery at Aalesund Hospital between
      January 2002 and July 2004. Incontinence was assessed by St Mark's score. The
      anal canal was assessed with three-dimensional endoanal sonography (EAUS).
      Sphincter defects were classified according to the Starck score and our new EAUS
      defect score. The EAUS images were interpreted by an observer blinded to other
      patient data. RESULTS: Sixty-one women were included in this study. Incontinence
      was reported by 32 (52%) women at a median of 21 (range, 9-35) months after
      delivery. Three-dimensional EAUS datasets were obtained in 55 women. There was a
      significant correlation between St Mark's score and our EAUS defect score (P =
      0.034), and correlation approached but did not reach significance between St
      Mark's score and the Starck score (P = 0.053). There was a strong correlation
      between our EAUS defect score and the Starck score (P < 0.001). CONCLUSIONS:
      There is a positive correlation between the extent of sphincter defects and the
      degree of anal incontinence following primary repair of obstetric sphincter
      tears. Our findings highlight the importance of adequate reconstruction of the
      anal sphincters during primary repair.

PMID- 18059078
TI  - Validation of a fully automated high throughput liquid chromatographic/tandem
      mass spectrometric method for roxithromycin quantification in human plasma.
      Application to a bioequivalence study.
AB  - A fully automated high-throughput liquid chromatography/tandem mass spectrometry
      (LC-MS/MS) method was developed for the determination of roxithromycin in human
      plasma. The plasma samples were treated by liquid-liquid extraction (LLE) in 2.2
      mL 96-deep-well plates. Roxithromycin and the internal standard clarithromycin
      were extracted from 100 microL of human plasma by LLE, using methyl t-butyl ether
      as the organic solvent. All liquid transfer steps were performed automatically
      using robotic liquid handling workstations. After vortexing, centrifugation and
      freezing, the supernatant organic solvent was evaporated and reconstituted.
      Sample analysis was performed by reversed-phase LC-MS/MS, with positive ion
      electrospray ionization, using multiple-reaction monitoring. The method had a
      very short chromatographic run time of 1.6 min. The calibration curve was linear
      for the range of concentrations 50.0-20.0x10(3) ng mL(-1). The proposed method
      was fully validated and it was proven to be selective, accurate, precise,
      reproducible and suitable for the determination of roxithromycin in human plasma.
      Therefore, it was applied to the rapid and reliable determination of
      roxithromycin in a bioequivalence study after per os administration of 300 mg
      tablet formulations of roxithromycin.

PMID- 18059079
TI  - Fetal adiponectin and resistin in correlation with birth weight difference in
      monozygotic twins with discordant growth.
AB  - BACKGROUND: Various studies have demonstrated an increased risk for adult
      diseases in newborns born small-for-gestational-age (SGA). Adiponectin and
      resistin can be detected in cord blood and are suggested to affect insulin
      resistance (IR). This might represent a link between metabolic syndrome and SGA
      birth. STUDY DESIGN: We investigated the relationship between the adipocytokines
      and inter-twin birth weight (BW) difference of 31 monozygotic twins with twin
      twin transfusion syndrome; in 14 twin pairs BW difference was >15% (1 SGA twin, 1
      appropriate-for-gestational-age, AGA, twin). RESULTS: BW and length of all
      patients were positively related to adiponectin (r = 0.57; p < 0.0001; r = 0.47;
      p < 0.0001) and to resistin (r = 0.31; p < 0.01; r = 0.35; p < 0.01). In 71%
      (10/14), the SGA twins showed lower adiponectin concentrations than their AGA co
      twins (only 6/14 for resistin). To correct for gestational age we calculated the
      relationship between the intrapair differences (Delta) of BW and Delta of the
      hormones. We found Delta BW positively correlated with adiponectin (r = 0.55; p <
      0.001) but not with resistin (r = 0.22; p = 0.2). Delta adiponectin was
      positively correlated with Delta resistin (r = 0.45; p < 0.01). CONCLUSION: These
      data demonstrate that adiponectin and resistin levels are associated with BW with
      only adiponectin levels being reduced in SGA children independently of
      gestational age. Prenatally different metabolic status between the twins might
      predispose the SGA twin to develop IR later in life.

PMID- 18059080
TI  - Diagnosis and management of hyperinsulinaemic hypoglycaemia of infancy.
AB  - Hyperinsulinaemic hypoglycaemia is a cause of persistent hypoglycaemia in the
      neonatal and infancy periods. Prompt recognition and management of patients with
      hyperinsulinaemic hypoglycaemia are essential, if brain damage and long-term
      neurological sequelae are to be avoided. Hyperinsulinaemic hypoglycaemia can be
      transient, prolonged, or persistent (congenital). Advances in the fields of
      molecular biology, genetics, and pancreatic beta-cell physiology are beginning to
      provide novel insights into the mechanisms causing congenital forms of
      hyperinsulinism. So far mutations in six different genes have been described that
      lead to unregulated insulin secretion. The histological differentiation of focal
      and diffuse congenital hyperinsulinism has radically changed the surgical
      approach to this disease. Until recently, highly invasive investigations were
      performed to localize the focal lesion, but recent experience with (18)F-L-dopa
      positron emission tomography scanning suggests that this technique is highly
      sensitive for differentiating diffuse from focal disease as well as for
      accurately locating the focal lesion. Despite recent advances, the genetic basis
      of congenital hyperinsulinism is still unknown in about 50% of the patients, and
      the management of medically unresponsive diffuse disease remains a real
      challenge.

PMID- 18059081
TI  - Similar biological medicinal products containing recombinant human growth
      hormone: European regulation.
AB  - The concept of similar biological medicinal products ('biosimilar' medicinal
      products) allows pharmaceutical companies to develop products based on an
      abridged dossier once the marketing protection of the 'reference' biological
      medicinal product has expired. A biosimilar medicinal product can be granted a
      marketing authorization provided that its similarity to a reference product is
      established in terms of quality, safety and efficacy (step-wise comparability
      exercise). A decision to launch a biosimilar medicinal product on the market is
      taken if it has a similar efficacy and comparable or better (less) immunogenicity
      than the chosen reference biological medicinal product. However, this decision is
      based on limited data and the comparability program may detect substantial
      differences in immunogenicity profiles but is likely incapable of detecting rare
      events. This is why clinical experience, through clinical trials and extensive
      pharmacovigilance programs, remains the most reliable way to assess the
      immunogenicity and tolerance profile of recombinant therapeutic proteins.
      Substitution of one biological medicinal product by a biosimilar medicinal
      product is not currently recommended before long-term clinical efficacy and
      safety have been acquired in all relevant populations. Here we review recent
      regulatory guidelines provided by EMEA and comment on the marketing
      authorizations and risk management plans of two recently approved biosimilar
      somatropins.

PMID- 18059082
TI  - Association of ADRB1 and UCP3 gene polymorphisms with insulin sensitivity but not
      obesity.
AB  - BACKGROUND: The uncoupling proteins (UCPs) and beta-adrenoceptors (ADRBs) are
      important for energy balance and may be involved in the pathogenesis of insulin
      resistance. Obesity is strongly hunted by insulin resistance and susceptibility
      genes for the two conditions could be separate or common. Variations within the
      UCPs and ADRBs genes may give important clues to their involvement in disease.
      METHODS: A total of four single nucleotide polymorphisms (SNPs) in the genes
      UCP1, UCP2, UCP3, and ADRB1 were examined for association with obesity and
      insulin sensitivity (HOMA(IR)) in obese (n = 292) and healthy non-obese (n = 481)
      females. RESULTS: None of the SNPs was associated with obesity status or body
      mass index. However, ADRB1 (rs1801253) was nominally associated with serum
      insulin (nominal p = 0.034) and HOMA(IR) (nominal p = 0.022). UCP3 (rs1800006)
      was in post-hoc analysis nominally associated with serum insulin and HOMA(IR)
      (nominal p = 0.013 and 0.048, respectively). UCP1 and UCP2 showed no association
      with insulin sensitivity. CONCLUSION: Polymorphisms in ADRB1 and UCP3 may
      contribute to insulin resistance rather than obesity among Swedish women.

PMID- 18059083
TI  - Early diagnosis and multidisciplinary care reduce the hospitalization time and
      duration of tube feeding and prevent early obesity in PWS infants.
AB  - BACKGROUND/AIMS: To describe and evaluate the impact of very early diagnosis and
      multidisciplinary care on the evolution and care of infants presenting with
      Prader-Willi syndrome (PWS). METHODS: 19 infants diagnosed with PWS before the
      second month of life were followed by a multidisciplinary team. Median age at the
      time of analysis was 3.1 years [range 0.4-6.5]. The data were compared with data
      collected in 1997 from 113 questionnaires filled out by members of the French PWS
      Association. The patients from this latter data set were 12.0 years [range 4
      months to 41 years] at the time of analysis, with a median age of 36 months at
      diagnosis. RESULTS: The duration of their hospitalization time was significantly
      reduced from 30.0 [range 0-670] to 21 [range 0-90] days (p = 0.043). The duration
      of gastric tube feeding was significantly reduced from 30.5 [range 0-427] to 15
      [range 0-60] days (p = 0.017). Growth hormone treatment was started at a mean age
      of 1.9 +/- 0.5 years in 10 infants and L-thyroxine in 6 infants. Only 1 infant
      became obese at 2.5 years. CONCLUSION: Early diagnosis combined with
      multidisciplinary care decreases the hospitalization time, duration of gastric
      tube feeding and prevents early obesity in PWS infants.

PMID- 18059084
TI  - An evaluation of the thyrotrophin-releasing hormone stimulation test in
      paediatric clinical practice.
AB  - AIM: The aim of this retrospective study was to evaluate the clinical usefulness
      of the thyrotropin-releasing hormone (TRH) test in children with suspected
      hypothalamic or pituitary dysfunction. METHODS: We reviewed the case notes of all
      patients in whom a TRH test had been performed over a 6-year period. Group 1 (n =
      85, 34 males, aged 0.9-18.8 years) was the reference group with no evidence of
      hypothalamic, pituitary or thyroid dysfunction. Group 2 (n = 42, 24 males, 0.1
      18.0 years) were being investigated for possible pituitary or hypothalamic
      insufficiency. RESULTS: In Group 1, thyrotropin (TSH) responses were higher in
      females than males (p < 0.01). In Group 2, TSH responses were normal for gender
      in 26 patients, subnormal in 5, and exaggerated/delayed in 11. Four patients with
      normal TSH responses and 4 with exaggerated/delayed responses had persistently
      low free thyroxine (FT(4)) or later developed low FT(4) and were treated with
      thyroxine. All those with subnormal TSH responses had normal FT(4) and were not
      treated. The TRH test did not reliably discriminate between hypothalamic and
      pituitary disorders. CONCLUSIONS: The TRH test did not give useful clinical
      information. Clinical decisions regarding thyroxine treatment were based on
      FT(4), not the TRH test. The TRH test should be abandoned in paediatric practice.

PMID- 18059085
TI  - A novel germline mutation, IVS4+1G>A, of the POU1F1 gene underlying combined
      pituitary hormone deficiency.
AB  - BACKGROUND: POU1F1 is a pituitary transcription factor that plays a pivotal role
      in pituitary development and expression of the GH, PRL and TSH beta genes.
      Therefore, abnormalities of the POU1F1 gene are known to be responsible for a
      phenotype causing combined pituitary hormone deficiency (CPHD) involving growth
      hormone, prolactin and thyrotropin. METHODS: We described an 18-year-old Thai
      man, from a consanguineous family, who presented with short stature and cognitive
      deficit. He underwent endocrinological and molecular investigations. RESULTS:
      Hormonal studies showed that the patient had GH deficiency and secondary
      hypothyroidism, consistent with CPHD. Direct DNA sequencing revealed a novel
      homozygous mutation at the splice site of exon 4, IVS4+1G>A. It is the first
      splice site mutation in the POU1F1 gene described to date. Of the 7 other family
      members studied for this mutation by restriction enzyme digestions, 5 were
      heterozygous. They were all unaffected, suggesting a recessive pattern of
      inheritance. CONCLUSIONS: We described a novel POU1F1 splice site mutation,
      IVS4+1G>A, the first of its kind, in a Thai patient with CPHD. Recessive
      inheritance is suggested. We also noted preventable morbidities which resulted
      from delay in diagnosis of concomitant pituitary hormone defects in newborns
      suspected of CPHD.

PMID- 18059086
TI  - Endocrine late effects of childhood cancer therapy: a report from the Children's
      Oncology Group.
AB  - Pediatric oncologists are curing increasing numbers of patients with childhood
      cancer, and most children diagnosed with a malignancy may now be expected to
      become long-term survivors. As the number of childhood cancer survivors grows, so
      too does the need for evidence-based surveillance of the long-term effects of
      cancer therapy. Long-term effects involving the endocrine system represent a
      frequent complication of therapy. The Children's Oncology Group Long-Term Follow
      Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers(COG
      LTFUG), most recently updated in 2006, provide a summary of the known endocrine
      late effects of surgery, radiation, chemotherapy, and stem cell transplant. This
      paper summarizes the scope and nature of the endocrine late effects of childhood
      cancer therapy based upon a review of the pertinent medical literature, and
      demonstrates how pediatric oncologists can use these guidelines in clinical
      practice.

PMID- 18059087
TI  - Familial glucocorticoid deficiency: advances in the molecular understanding of
      ACTH action.
AB  - Familial glucocorticoid deficiency (FGD), otherwise known as hereditary
      unresponsiveness to ACTH, is a rare autosomal recessive disease characterized by
      glucocorticoid deficiency in the absence of mineralocorticoid deficiency.
      Mutations of the ACTH receptor, also known as the melanocortin-2 receptor (MC2R),
      account for approximately 25% of FGD cases. More recently a second gene, MRAP
      (melanocortin-2 receptor accessory protein), was identified and found to account
      for a further 15-20%. MRAP encodes a small single transmembrane domain protein,
      which is essential in the trafficking of the MC2R to the cell surface. In this
      review, we will firstly summarize the clinical presentation and genetic aetiology
      of this condition. Secondly, we will discuss how the discovery of MRAP has
      enhanced our understanding of the mechanisms of ACTH/MC2R action. Finally, we
      will explore future developments in this field.

PMID- 18059088
TI  - Role of fasting plasma glucose, glycated haemoglobin and homeostatic model
      assessment in the detection of glucose intolerance in adult hypopituitary
      patients during growth hormone replacement therapy.
AB  - AIMS: This study was designed to determine the sensitivity and specificity of
      conventional criteria for diagnosis of impaired glucose tolerance (IGT) in a high
      risk population of GH-treated GH deficient (GHD) adults. METHODS: 33
      hypopituitary GHD patients with HbA(1c) >5.1% and 13 gender- and age-matched
      control GHD patients were selected. Oral glucose tolerance test (OGTT), fasting
      plasma glucose (FPG), HbA(1c), and homeostatic model assessment (HOMA) parameters
      were determined in all patients. Receiver operator characteristic curves were
      used to determined sensitivity and specificity for the detection of glucose
      intolerance as defined by plasma glucose >7.8 mmol/l at 120 min during OGTT.
      RESULTS: Sensitivity and specificity for this purpose for HbA(1c) (>5.1%) were 89
      and 17%; for FPG (>5.5 mmol/l): 78 and 67%; for FPG (>6.1 mmol/l): 56 and 89%;
      for HOMA-derived beta-cell function (betaCF) (<40%): 78 and 58%; for HOMA-derived
      insulin sensitivity (IS) (<70%): 11 and 89%, and for betaCF-IS hyperbolic product
      (betaCF-IS) (<54%): 89 and 75%, respectively. CONCLUSIONS: This study shows that
      FPG (>5.5 mmol/l) and betaCF-IS have high sensitivity and relatively high
      specificity for the detection of IGT and confirms that measurement of FPG or
      calculation of betaCF-IS provides appropriate safety surveillance in
      hypopituitary patients on GH replacement.

PMID- 18059089
TI  - Subclassification of small for gestational age children with persistent short
      stature: growth patterns and response to GH treatment.
AB  - AIM: We determined whether subclassification of short small for gestational age
      (SGA) children according to birth anthropometrics could delineate different
      patterns in gestation, delivery, postnatal growth, response to growth hormone
      (GH) treatment and parental height. METHODS: 201 short SGA children were divided
      into three groups, SGA(L), SGA(L+W) and SGA(L+W+HC), according to birth length
      (L), weight (W) and head circumference (HC) < or =-2.00 standard deviation score
      (SDS). RESULTS: SGA(L+W+HC) children were born after the shortest gestational age
      and more often by caesarean section than SGA(L) children (36.3 vs. 38.1 weeks,
      68.4 vs. 24.4%). SGA(L+W) children had an intermediate pattern and experienced
      most gestational hypertension (p = 0.01). At birth, SGA(L+W+HC) children were
      shorter than SGA(L) or SGA(L+W) (-4.12 vs. -2.67 and -3.72 SDS, p < or = 0.001).
      During the first 3 years of life, SGA(L+W+HC) children exhibited an increased
      growth in height (0.98 SDS) and HC (1.28 SDS) than SGA(L) (height, -0.06 SDS; HC,
      -0.30 SDS) and SGA(L+W) (height, 0.62 SDS; HC, -0.31 SDS). However, HC SDS
      remained smaller for SGA(L+W+HC) than the other groups at age 3. The groups did
      not differ in growth response during GH treatment. SGA(L) children tended to have
      shorter parents and target height than SGA(L+W+HC) children. CONCLUSIONS: Our
      study shows that subclassification of short SGA children might be a useful method
      for investigating SGA children as the subgroups revealed a different gestation,
      delivery and postnatal growth pattern. Response to GH treatment was not different
      between the groups.

PMID- 18059090
TI  - Longitudinal study of the maternal insulin-like growth factor system before,
      during and after pregnancy in relation to fetal and infant weight.
AB  - BACKGROUND: The maternal insulin-like growth factor (IGF) system is considered to
      be involved in fetal growth regulation. However, available data linking this
      system to fetal growth are contradictory and incomplete. AIMS: To measure
      components of the IGF system before, during and after pregnancy in healthy women
      and to relate these results, and their changes during pregnancy, to fetal weight
      (gestational week 31) and birth weight. METHODS: Serum concentrations of IGF-I,
      IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-3 and IGFBP-3 protease activity were
      assessed in 23 women before conception, at weeks 8, 14, 20, 32 and 35 of
      pregnancy and 2 weeks postpartum. The data were analyzed using simple and
      multiple linear regression. RESULTS: One third of the variability in fetal weight
      was explained by IGF-I in combination with IGFBP-3 protease activity, both
      assessed at gestational week 32 (p = 0.013). Birth weight was negatively
      correlated (r = -0.43 to -0.59) with IGFBP-1 at gestational week 20 (p = 0.041),
      32 (p = 0.012) and 35 (p = 0.003). CONCLUSION: We propose there is a finely tuned
      balance among the components of the IGF system, providing a means for fetal
      growth regulation.

PMID- 18059091
TI  - Type 2 diabetes in children and adolescents in a 2-year follow-up: insufficient
      adherence to diabetes centers.
AB  - BACKGROUND/AIMS: To study the 2-year course of children and adolescents with type
      2 diabetes mellitus (T2DM) in general practice to present (1) the treatment
      modalities, (2) patient adherence, and (3) the occurrence of comorbidities.
      METHODS: HBA1c, lipids, blood pressure, treatment modalities, occurrence of
      retinopathy and nephropathy were analyzed in 129 children and adolescents with
      T2DM (median age 13.4 years, 75% female) in specialized diabetes centers in
      Germany. RESULTS: Seventy-eight (60%) children dropped out of care after a mean
      of 7.1 months. Drug treatment was not stopped in any of the 64 children initially
      treated with antidiabetic drugs. Sixteen (12%) children were treated solely by
      lifestyle intervention over the 2-year course. In the 51 children with complete
      follow-up, median HbA1c was 7.7% at diagnosis and 6.3% after 2 years. Less than
      5% of all children were treated with antihypertensive or lipid-lowering drugs,
      while 65% suffered from hypertension and 44% from dyslipidemia. Over the course
      of the disease, retinopathy was not observed, while microalbuminuria occurred in
      25%. CONCLUSIONS: In general practice, many children and adolescents with T2DM
      were lost of follow-up. Lifestyle intervention as sole treatment was not often
      useful for long-term metabolic control. Dyslipidemia and hypertension were seldom
      treated as recommended.

PMID- 18059092
TI  - Gene expression profiling of hypothalamic hamartomas: a search for genes
      associated with central precocious puberty.
AB  - BACKGROUND: Hypothalamic hamartomas (HHs) are congenital lesions composed of
      neurons and astroglia. Frequently, HHs cause central precocious puberty (CPP)
      and/or gelastic seizures. Because HHs might express genes similar to those
      required for the initiation of normal puberty, we used cDNA arrays to compare the
      gene expression profile of an HH associated with CPP with three HHs not
      accompanied by sexual precocity. METHODS: Global changes in gene expression were
      detected using Affymetrix arrays. The results were confirmed by semiquantitative
      PCR, which also served to examine the expression of selected genes in the
      hypothalamus of female monkeys undergoing puberty. RESULTS: All HHs were
      associated with seizures. Ten genes whose expression was increased in the HH with
      CPP were identified. They encode proteins involved in three key cellular
      processes: transcriptional regulation, cell-cell signaling, and cell
      adhesiveness. They include IA-1 and MEF2A, two transcription factors required for
      neuronal development; mGluR1 and VILIP-1, which encode proteins involved in
      neuronal communication, and TSG-6 that encodes a protein involved in cell
      adhesiveness. Of these, expression of mGluR1 also increases in the female monkey
      hypothalamus at puberty. CONCLUSIONS: Increased expression of these genes in HHs
      may be relevant to the ability of some HHs to induce sexual precocity.

PMID- 18059093
TI  - Novel SHOX gene mutation in a short boy with Becker muscular dystrophy: double
      trouble in two adjacent genes.
AB  - Short stature is a well-recognized feature of Duchenne muscular dystrophy, whilst
      it has been reported rarely in Becker muscular dystrophy (BMD). Here we report
      two brothers with BMD, who exhibited a very different growth pattern. Whereas in
      the short brother (-2.2 SDS) molecular investigation revealed a G367A mutation in
      the short stature homeobox containing (SHOX) gene located in the Xp22.3 region,
      no abnormality was found in the brother with normal height (-0.1 SDS). Our data
      suggest that abnormal growth observed in a boy with BMD may be related to an
      additional genetic alteration, already known as correlated with short stature.

PMID- 18059094
TI  - Statistics in biomedical laboratory and clinical science: applications, issues
      and pitfalls.
AB  - This review is directed at biomedical scientists who want to gain a better
      understanding of statistics: what tests to use, when, and why. In my view, even
      during the planning stage of a study it is very important to seek the advice of a
      qualified biostatistician. When designing and analyzing a study, it is important
      to construct and test global hypotheses, rather than to make multiple tests on
      the data. If the latter cannot be avoided, it is essential to control the risk of
      making false-positive inferences by applying multiple comparison procedures. For
      comparing two means or two proportions, it is best to use exact permutation tests
      rather then the better known, classical, ones. For comparing many means, analysis
      of variance, often of a complex type, is the most powerful approach. The
      correlation coefficient should never be used to compare the performances of two
      methods of measurement, or two measures, because it does not detect bias. Instead
      the Altman-Bland method of differences or least-products linear regression
      analysis should be preferred. Finally, the educational value to investigators of
      interaction with a biostatistician, before, during and after a study, cannot be
      overemphasized.

PMID- 18059095
TI  - Evaluation of the impact of the Kuwait Diabetes Care Program on the quality of
      diabetes care.
AB  - OBJECTIVES: To evaluate the impact of the Kuwait Diabetes Care Program on the
      quality of care provided for diabetic patients in the Primary Health Care
      setting. MATERIALS AND METHODS: The Kuwait Diabetes Care Program developed,
      published and disseminated clinical practice guidelines, conducted training
      courses, standards for diabetes care, and introduced a monitoring and evaluation
      system. Four audits (September 1999, October 2001, 2002 and 2003) were carried
      out at five diabetic clinics. September 1999 referred to in this study as first
      (baseline) audit was prior to the introduction of the clinical practice
      guidelines. The three other audits were performed to assess adherence with the
      guidelines in the administrative management of patients' records and
      implementation of the standards. Two hundred and fifty patients were involved in
      the study. RESULTS: The proportion of patients with organized, structured files
      increased significantly from 60.0 to 100.0% (p < 0.001), and recording of
      patients' demographic data increased from 38.6 to 95.6% (p < 0.001). Use of
      structured visit sheets, proper fixation of the laboratory and prescription
      sheets had also improved significantly. The prevalence of smoking assessment,
      fundus examination, and foot examination increased significantly from 2.8 to
      27.2% (p < 0.001); 2.4 to 31.6% (p < 0.001); 0.4 to 40.4% (p < 0.001),
      respectively. The prevalence of measuring urinary microalbumin, serum creatinine
      and HbA(1c) increased significantly from 4.4 to 26.4% (p < 0.001); 16.0 to 78.4%
      (p < 0.001), and 10.4 to 60.8% (p < 0.001), respectively. The prevalence of
      measuring serum total cholesterol, triglycerides, HDL-C, and LDL-C levels
      increased significantly from 16.4 to 80.0% (p < 0.001); 14.4 to 80.0% (p <
      0.001); 2.4 to 32.8% (p < 0.001), and 2.4 to 24.0% (p < 0.001), respectively.
      CONCLUSION: This audit shows that a national diabetes program was associated with
      improved processes of diabetes care. Further, support from health authorities,
      provision of manpower resources, a continuing monitoring and evaluation system,
      and conduction of structured education programs may lead to further improvements
      in the quality of diabetes care.

PMID- 18059096
TI  - Pulmonary ventilatory functions and obesity in Kuwait.
AB  - OBJECTIVE: To study the relationship between obesity and pulmonary ventilatory
      functions in Kuwaiti adults. SUBJECTS AND METHODS: A total of 200 male and 180
      female Kuwaiti adults aged 20-65 years were investigated in six medical centers
      from April 2004 to March 2006. Parameters measured included forced expiratory
      volume in 1 s (FEV(1)), forced vital capacity (FVC), FEV(1) as a percentage of
      FVC (FEV%); body mass index (BMI in kg/m(2)) and waist-to-hip ratio (W/H).
      RESULTS: For the whole group, males or females, BMI (kg x m(2)) and W/H were poor
      individual predictors of pulmonary ventilatory functions. However, central
      adiposity (W/H) was associated with restrictive respiratory impairment (10.6
      13.9% decrease in FEV(1) and 10-12.3% decrease in FVC), independent of sex, age
      or height. In obese females and males (BMI >30), increasing severity of obesity
      was significantly (p < 0.05, R(2) >0.6) [corrected] associated with increasing
      restrictive respiratory impairment (8.7-14.4% decrease in FEV(1) and 8-11.7%
      decrease in FVC), with no evidence of obstructive disease (FEV(1)/FVC >0.8).
      CONCLUSION: In adult Kuwaiti males and females, increase in body fat at BMI >30
      or W/H >1 was associated with a restrictive effect on pulmonary ventilation.

PMID- 18059097
TI  - Self-monitoring of blood pressure and the role of community pharmacists in
      Kuwait.
AB  - OBJECTIVE: To determine the types of devices for self-monitoring of blood
      pressure available to consumers in Kuwait and the pharmacists' knowledge and
      level of information provided to consumers when purchasing such devices.
      MATERIALS AND METHODS: It was possible to contact 196 of the 230 eligible
      pharmacies from five governorates in Kuwait. Ten of these were used to pretest
      the questionnaire and six declined to participate. Another six did not carry any
      blood pressure monitoring devices and hence were excluded. Data was then
      collected from pharmacists at the 174 remaining community pharmacies via face-to
      face structured interview of the respondents at their work sites. RESULTS: Of the
      174 pharmacists, 173 (99.4%) claimed to offer or provide advice to clients at the
      time of purchasing devices, 117 (67.1%) of them stating that they did so even if
      the patients did not ask. Although 147 (84.5%) respondents correctly identified
      the mercury sphygmomanometer as the most reliable device for measuring blood
      pressure, less than half (86, 49.4%) claimed to know how to check the accuracy of
      the devices they sold. Only 25 (14.4%) pharmacists could actually identify the
      correct procedure for checking the accuracy of the devices and only 25 (14.4%)
      pharmacists could correctly identify cutoff points for systolic and diastolic
      blood pressure delineating clinical hypertension. Only 1 pharmacist could
      correctly name a reference source for blood pressure measurement. CONCLUSION:
      There is a need for improvement of community pharmacists' competence in
      supporting patients and in providing them with information regarding devices for
      measuring blood pressure in Kuwait.

PMID- 18059098
TI  - Prevalence and antimicrobial susceptibility pattern of extended-spectrum beta
      lactamase-producing Enterobacteriaceae in the United Arab Emirates.
AB  - OBJECTIVE: To investigate the prevalence and antibiotic susceptibility pattern of
      extended-spectrum beta-lactamases (ESBL)-producing Enterobacteriaceae among
      patients in the United Arab Emirates. MATERIALS AND METHODS: A total of 130
      Enterobacteriaceae comprising of Escherichia coli (n = 83), Klebsiella pneumoniae
      (n = 45) and Klebsiella oxytoca (n = 2) was studied. Of these 130 isolates, 64
      were from urine. ESBL screening was by disc diffusion and confirmatory tests for
      ESBL phenotype were conducted using BD Phoenix ESBL System and
      cephalosporin/clavulanate combination discs. Susceptibility to a panel of
      antibiotics was evaluated. RESULTS: Of the 130 isolates, 53 (41%) were identified
      as having ESBL phenotype; of these, 32 (60%) were E. coli, 20 (36%) K. pneumoniae
      and 2 (4%) K. oxytoca. ESBL phenotype was seen in 100% of endotracheal tubes
      isolates, 20 (31%) from urine, 7 (58%) from blood and 4 (80%) from catheter tips.
      Amikacin susceptibility was 100%. Over 90% of ESBL isolates showed resistance to
      aztreonam and cephalosporins. All Klebsiella isolates were carbapenem sensitive.
      One ESBL isolate showed intermediate resistance to imipenem and meropenem (both
      MIC 8 microg/ml), cefotetan (MIC 32 microg/ml) and piperacillin/tazobactam (MIC
      32 microg/ml). MIC for the carbapenems was lower in non-ESBL isolates (0.034
      microg/ml) than ESBL isolates (0.071 microg/ml). Resistance to gentamicin,
      ciprofloxacin and piperacillin/tazobactam was higher in ESBL than non-ESBL
      isolates (p < 0.05). CONCLUSION: A high prevalence of ESBL-producing bacteria
      exists among in-patients in the United Arab Emirates. Amikacin and carbapenems
      remain the most effective drugs, but the presence of carbapenem-resistant ESBL
      producing E. coli and occurrence of multidrug resistance are of concern.
      Continued surveillance and judicious antibiotic usage are recommended.

PMID- 18059099
TI  - Transdermal permeation of trimetazidine from nerodilol-based HPMC gel drug
      reservoir system across rat epidermis.
AB  - OBJECTIVE: To study the in vitro transdermal permeation of trimetazidine from
      hydroxypropylmethyl cellulose (HPMC) gel drug reservoir system using nerodilol as
      a penetration enhancer. MATERIALS AND METHODS: An HPMC gel containing selected
      concentrations of nerodilol (0, 2, 4 or 5% w/v) and 2.5% w/v of trimetazidine was
      prepared, and subjected to in vitro permeation studies across rat epidermis. The
      amount of trimetazidine permeated at different time intervals (1, 2, 4, 8, 12, 18
      and 24 h) was estimated, and the data were analyzed to calculate various
      permeation parameters. RESULTS: There was an increase in the amount of
      trimetazidine (8,719.7 +/- 153.3 microg/cm(2))permeated across the rat epidermis
      up to 24 h (Q(24)) with an increase in nerodilol concentration (5% w/v) in HPMC
      gel drug reservoir. However, no significant difference (p > 0.05) was observed in
      the amount of drug permeated (Q(24)) with 5% w/v of nerodilol when compared to
      that obtained with 4% w/v of nerodilol (8,484.5 +/- 165.8 microg/cm(2)).
      Nerodilol, at a concentration of 4% w/v enhanced the flux of trimetazidine across
      rat epidermis by about 1.96 times when compared to control. CONCLUSION: The HPMC
      gel drug reservoir containing 4% w/v of nerodilol showed optimal transdermal
      permeation of trimetazidine.

PMID- 18059100
TI  - Spectrum of cutaneous vasculitis in adult patients from the Farwaniya region of
      Kuwait.
AB  - OBJECTIVE: To determine the clinical profile, etiologic factors, disease
      associations, and the laboratory profile of adult patients with cutaneous
      leukocytoclastic vasculitis (LV) presenting to the Dermatology Department at
      Farwaniya Hospital, Kuwait. SUBJECTS AND METHODS: The medical records of 57 adult
      patients (>18 years) with biopsy-proven cutaneous LV from January 2004 to June
      2006 at Farwaniya Hospital were reviewed. RESULTS: Of the 57 patients studied, 21
      (36.8%) were classified as having primary cutaneous small vessel vasculitis. The
      most common type of skin lesions found was palpable purpura seen in 29 (50.9%)
      patients. No possible cause for the cutaneous vasculitis could be identified in
      21 patients. Extracutaneous involvement was seen in 32 (56.1%) patients of which
      29 had joint involvement. The most frequent laboratory abnormality was an
      elevated erythrocyte sedimentation rate (ESR). Altered laboratory evaluation in
      the form of leukocytosis, raised antistreptolysin O titers and urine
      abnormalities were found in association with systemic vasculitis. IgA deposits
      were present in 33 patients. Risk factors for chronicity of cutaneous LV were
      female sex, advanced age, unidentified etiology, absence of fever and presence of
      joint involvement. CONCLUSION: The commonest type of LV in Kuwait is primary
      cutaneous small vessel vasculitis. The most frequent laboratory abnormality
      associated with LV was increased ESR.

PMID- 18059101
TI  - Legionella in clinical specimens and hospital water supply facilities: molecular
      detection and genotyping of the isolates.
AB  - OBJECTIVE: To evaluate genus- and species-specific polymerase chain reactions
      (PCRs) for the detection of the genus Legionella and the species Legionella
      pneumophila in clinical specimens and hospital water supplies, and to establish a
      simple and reproducible random amplification of polymorphic DNA (RAPD)-PCR
      technique for genotyping of Legionella. MATERIALS AND METHODS: A total of 70
      respiratory tract specimens(bronchoalveolar lavage: n = 46; endotracheal
      secretions: n = 9; sputum: n = 15) from patients with atypical pneumonia, and 283
      environmental samples (water: 20; swabs: 263) collected from water storage and
      supply facilities of the Mubarak Al-Kabeer Hospital, Kuwait, were tested by
      culture and genus-specific PCR for the detection of Legionella. The L.
      pneumophila isolates were subsequently typed by serology and RAPD-PCR using
      serotype-specific sera and arbitrary primers, respectively. RESULTS: Of the 70
      clinical samples, culture yielded 2 (2.9%) whereas genus-specific PCR detected
      Legionella in 20 (28.6%) samples. The 2 culture-positive specimens were also
      positive for L.-pneumophila-specific PCR. Testing of swab and water samples by
      culture and genus-specific PCR yielded 61 (21.6%) and 67 (23.7%) positive
      samples, respectively. All of the 61 culture-positive samples were also positive
      by genus-specific PCR and 45 of them were positive for L.-pneumophila-specific
      PCR. Serological typing of 43 L. pneumophila isolates showed that 8 of these
      belonged to serotype 1 and 35 to serotype 3; however, RAPD-PCR analyses
      demonstrated polymorphisms among the isolates of both serotypes. CONCLUSION: A
      higher association between PCR and culture was observed for the environmental
      samples than for the clinical samples. The application of genus- and species
      specific PCRs and RAPD is useful in the detection and typing of Legionella in
      clinical and environmental samples.

PMID- 18059102
TI  - Overlapping repair in patients with anal sphincter injury.
AB  - OBJECTIVE: The aim of this study was to demonstrate the improvement of anal canal
      function after overlap sphincter repair and confirm that this treatment option is
      superior in patients with nonobstetric sphincter damage. SUBJECTS AND METHODS:
      From 1998 to 2003, 44 women who underwent overlapping sphincter repair were
      enrolled in this study. The women were allocated to one of two groups, obstetric
      trauma (n = 31) and nonobstetric (perineal) trauma (n = 13). Both groups were
      compared in terms of age, operation time, number of deliveries, hospital stay,
      need for analgesics, complication rate, pre- and postoperative outcomes of anal
      manometry and quality of life, using the fecal incontinence severity index and a
      questionnaire for fecal disorders. RESULTS: Anal canal length was significantly
      extended postoperatively in both groups compared to preoperative length. Eight
      week postoperative resting and squeeze pressures were significantly higher than
      preoperative pressures in both patients with nonobstetric and obstetric sphincter
      injury. Although significant increase was seen in both groups, the mean
      postoperative resting and squeeze pressures at 1 year were rather high in
      patients with nonobstetric sphincter injury. At the end of a year of follow-up,
      overall satisfaction of the repair was about 82%. CONCLUSION: Overlap sphincter
      repair was feasible, although patient satisfaction was slightly less in the
      obstetric than in the nonobstetric trauma group. The improvement of anal function
      at 20- to 24-month follow-up is attributed to both high squeeze pressure and
      broad anal canal.

PMID- 18059103
TI  - Frequency of abnormal thyroid function tests in Kuwaiti Arabs with autoimmune
      diseases.
AB  - OBJECTIVES: The purpose of this study was to examine the frequencies of abnormal
      thyroid function tests and serum thyroid autoantibodies in healthy Kuwaitis and
      those with autoimmune diseases. SUBJECTS AND METHODS: Serum concentrations of
      sensitive thyrotropin, and free thyroxine were measured in 577 apparently healthy
      controls, 177 patients with rheumatoid arthritis (RA), 60 with systemic lupus
      erythematosus (SLE) and 25 with primary Sjogren's syndrome (pSS) using the
      immunochemiluminescent assay method on IMMULITE 1000. Serum microsomal and
      thyroglobulin autoantibodies were also measured by passive hemagglutination
      assay. For analysis of the thyroid function tests, the subjects were classified
      into five categories: normal, subclinical hypothyroidism, overt hypothyroidism,
      euthyroid sick syndrome and biochemical hyperthyroidism. RESULTS: Subclinical
      hypothyroidism was seen in 1.7% of healthy controls, 10.2% of RA, 13.3% of SLE,
      and 16% of pSS patients. Among RA patients, the frequency of subclinical
      hypothyroidism in females (11.4%) was significantly higher than among males
      (5.4%; p < 0.01). In SLE and pSS patients, all those with subclinical
      hypothyroidism were females. Overt hypothyroidism was seen in 1.4% of controls,
      10.2% of RA, 8.3% of SLE, and 4% of pSS patients. Biochemical hyperthyroidism was
      seen in 0.2% of controls, 4.5% of RA, 5% of SLE and none of pSS patients. The
      euthyroid sick syndrome was seen in 0.4% of controls, 13.6% of RA, 16.7% of SLE
      and in none of pSS patients. Thyroid autoantibodies were present in 3.1% of
      controls, 12.4% of RA, 18.3% of SLE, and 12% of pSS patients. CONCLUSION: Our
      data show that abnormal thyroid function tests and thyroid autoantibodies occur
      frequently in Kuwaitis with autoimmune diseases. Therefore, ordering these tests
      in these diseases is recommended.

PMID- 18059104
TI  - Is combined pretransplantation seropositivity of kidney transplant recipients for
      cytomegalovirus antigens (pp150 and pp28) a predictor for protection against
      infection?
AB  - OBJECTIVE: This study was aimed at detecting antibodies to the antigens which may
      contribute to protection against cytomegalovirus (CMV) infection after organ
      transplantation. MATERIALS AND METHODS: A total of 203 kidney transplant patients
      were enrolled in the study. Based on CMV antigenemia assay, 23 patients were
      antigen-positive and of the remaining 180 antigen-negative patients, 46 were
      selected as controls matched for age, gender and source of kidney. The 69 kidney
      recipients (KR) had CMV antibody due to previous infection and were followed up
      for a period of 6 months after transplantation for the development of active CMV
      infections by the antigenemia assay. Antibody responses to five CMV-related
      peptide antigens (pp65, gB, pp150, pp28 and pp38) were investigated by enzyme
      immunoassay and their presence was correlated with the results of the CMV
      antigenemia assay. RESULTS: Of the five CMV-related peptide antigens, only gB
      antigen showed response to the antibody in 10/23 (43.5%) antigen-positive
      patients and 9/46 antigen-negative patients and the difference was statistically
      significant (p = 0.048). On the other hand, there was no significant difference
      in antibody responses between the antigen-positive and antigen-negative KR to the
      other four CMV peptide antigens (p > 0.05). However, among the antigen-positive
      KR there was only 1 patient who had antibodies to both pp150 and pp28 antigen,
      while among the antigen-negative KR, 22 of 46 (47.8%) had the antibodies (p <
      0.001). CONCLUSION: The findings suggest that the combined presence of antibodies
      against the pp150 and pp28 antigens may indicate a lower risk of CMV reactivation
      after kidney transplantation.

PMID- 18059106
TI  - Pooled analysis of 2,408 cases of acute adult purulent meningitis from Turkey.
AB  - OBJECTIVES: The aim of this study was to systematically review the Turkish
      literature of acute adult purulent meningitis. MATERIALS AND METHODS: The
      published series of three national databases and two international databases were
      searched to perform the review. In addition to the databases, abstracts of
      congresses held between 1994 and 2003 by the Turkish Clinical Microbiology and
      Infectious Diseases Association, Turkish Microbiology Association, and the
      Antibiotic and Chemotherapy Association were searched for reports about acute
      purulent meningitis. RESULTS: Data for 2,408 patients with a diagnosis of acute
      purulent meningitis were obtained from 30 reports. In terms of clinical findings,
      1,254 of 1,570 (79.8%) had fever (>38 degrees C), 1,408 of 1,595 (88.2%)
      headache, 1,403 of 1,562 (89.8%) stiffness of the neck, and 649 of 784 (82.7%)
      leukocytosis (>10,000/mm(3)). Cerebrospinal fluid culture yielded a pathogen in
      873 of 2,260 (38.6%) patients. The most common pathogen was Streptococcus
      pneumoniae, followed by Neisseria meningitidis and Staphylococcus aureus. Overall
      mortality was 425 of 2,408 (17.6%). Pathogen-specific mortality was 60 of 202
      (29.7%) for S. pneumoniae and 6 of 100 (6%) for N. meningitidis. CONCLUSION:
      Meningitis is a serious, life-threatening disease. More preventive measures
      should be sought to further decrease the mortality and morbidity related to acute
      purulent meningitis.

PMID- 18059105
TI  - Surveillance of antibacterial resistance in Staphylococcus aureus isolated in
      Kuwaiti hospitals.
AB  - OBJECTIVE: To investigate the prevalence of antibiotic resistance among
      Staphylococcus aureus isolated in Kuwaiti hospitals. MATERIALS AND METHODS: S.
      aureus were isolated and identified following standard microbiological methods.
      Antibacterial susceptibility test was performed by disk diffusion and the
      measurement of minimum inhibitory concentration with E-test strips. RESULTS: A
      total of 1,846 S. aureus isolates were analyzed from 13 hospitals between 1 March
      and 30 October 2005. They were isolated from 1,765 (95.6%) inpatients and 81
      (4.4%) outpatients. Methicillin resistance was detected in 588 (32.0%) of the
      isolates. The methicillin-resistant S. aureus (MRSA) consisted of 461 (78%)
      multiresistant and 127 (22%) nonmultiresistant isolates. The nonmultiresistant
      MRSA consisted of epidemic MRSA-15 and community-associated MRSA. The community
      associated MRSA was detected in all hospitals with MRSA, indicating its
      establishment in Kuwaiti hospitals. The proportion of isolates resistant to
      gentamicin, kanamycin, erythromycin, tetracycline, ciprofloxacin, fusidic acid
      and trimethoprim was higher among MRSA than methicillin-susceptible S. aureus
      (MSSA) isolates. Twenty-four and 22% of MRSA and MSSA isolates, respectively,
      expressed reduced susceptibility to vancomycin (minimum inhibitory concentration
      = 3-4 mg/l). CONCLUSION: The study revealed the presence of methicillin
      resistance in 32% of S. aureus isolated in Kuwaiti hospitals and revealed an
      increase in the number of MRSA and MSSA with reduced susceptibility to
      vancomycin.

PMID- 18059107
TI  - Morphometric study of a horseshoe kidney.
AB  - OBJECTIVE: To describe a horseshoe kidney, a congenital anomaly of the upper
      urinary tract. CLINICAL PRESENTATION: A case study of horseshoe kidney harvested
      from a 62-year-old cadaver at Gazi University Medical School is presented.
      RESULTS: The right and left kidneys were fused at their lower poles by a
      parenchymal isthmus located ventral to the abdominal aorta and formed a U-shape
      with two unequal arms. The isthmus of the ectopic kidney was placed obliquely to
      the left at the level of the fourth and fifth lumbar vertebra. The left kidney
      was larger and longer than the right one. The kidneys were supplied by three
      renal arteries arising from the abdominal aorta. Two arteries on the right side
      supplied blood of the two kidneys, while the third artery that directly
      originated from the aorta, above the origin of inferior mesenteric artery,
      supplied the isthmus. Venous drainage of the both kidneys and the isthmus were
      drained by three veins that opened independently into the inferior vena cava. The
      right ureter was duplicated in origin. CONCLUSION: This report shows that
      knowledge of anomalies such as this is very important in planning and conducting
      surgical procedures.

PMID- 18059108
TI  - Ewing's sarcoma as second malignant neoplasm after retinoblastoma: a case report.
AB  - OBJECTIVES: To report a case of a child with the hereditary form of unilateral
      retinoblastoma (RB), who developed Ewing's sarcoma of the right fibula 3 years
      after the enucleation of the right eye. CASE PRESENTATION AND INTERVENTION: The
      child was diagnosed as a case of RB of the right eye at the age of 9 months. He
      was fully investigated and found to have locally advanced RB with bone marrow
      involvement (Reese-Ellsworth stage IVA). Enucleation was recommended to the
      family, but they refused. The patient received chemotherapy and diode laser
      thermotherapy in Kuwait and the UK. He had a local relapse after 11 months and
      subsequently underwent enucleation of the right eye. After 3 years, he was
      investigated for a small swelling in his right lower leg. After extensive
      investigations, it was reported as Ewing's sarcoma. He was treated with
      chemotherapy, surgery (complete excision of the fibula) and high-dose
      chemotherapy followed by autologous stem cell transplantation. The child is now
      nearly 2 years after completing the treatment and is disease free. CONCLUSIONS:
      This case confirms the increased risk of a second malignant neoplasm (SMN) in
      children with hereditary RB. These children need a very close follow-up for the
      early diagnosis of SMNs or even subsequent malignancies.

PMID- 18059109
TI  - Spontaneous rupture of a giant diaphragmatic hydatid cyst into the intrapleural
      space.
AB  - OBJECTIVE: We report a case of giant diaphragmatic hydatid cyst which ruptured
      spontaneously into the intrapleural space in a patient with coexistent giant
      hepatic hydatid cyst. CLINICAL PRESENTATION AND INTERVENTION: A 62-year-old
      female was admitted for dyspnea, nausea, vomiting, and right thoracic pain.
      Clinical findings, laboratory and radiological examinations including multislice
      computed tomography scan were consistent with the diagnosis of a giant
      diaphragmatic hydatid cyst which ruptured into the intrapleural space. Surgical
      intervention was performed through thoracotomy and phrenotomy in a one-stage
      operation for both cysts. CONCLUSION: This case shows that hydatid cysts of the
      diaphragm can rupture into the intrapleural space spontaneously. One-stage
      operation through thoracotomy may be successful for the surgical intervention for
      diaphragmatic hydatid cysts with coexistent hepatic cyst.

PMID- 18059111
TI  - Shortened hemofilter survival time due to lipid infusion in continuous renal
      replacement therapy.
AB  - BACKGROUND: Continuous renal replacement therapy is widely used for the treatment
      of critically ill patients with acute renal failure in critical care units. The
      survival time of the extracorporeal circuit is an important factor in providing
      renal replacement therapy. Despite rigorous efforts to maintain hemofilter
      patency, clinicians are occasionally faced with an unexplained short circuit
      survival time. METHODS: We present a critically ill patient undergoing continuous
      venovenous hemofiltration with regional citrate anticoagulation for management of
      acute renal failure in the context of sepsis. Once the patient was started on
      lipid infusion as part of total parenteral nutrition, we observed a shortened
      circuit survival due to premature hemofilter failure necessitating frequent
      changes of the hemofilter. The known potential causes for this phenomenon were
      ruled out. RESULTS: Evaluation revealed grossly lipemic serum associated with
      severe hypertriglyceridemia. Discontinuation of the lipid infusion was followed
      by a rapid return of circuit survival time to its baseline. Evaluation of the
      hemofilter by electron microscopy revealed that the rapid blockage of the hollow
      fibers was caused by lipid microparticles and fibrin deposits. CONCLUSION: Since
      total parenteral nutrition is commonly administered to malnourished and
      hypercatabolic critically ill patients on continuous renal replacement therapy,
      we suggest that intravenous lipid therapy might be a previously unreported and
      unappreciated remediable cause of premature hemofilter failure.

PMID- 18059110
TI  - Sporadic culture-negative peritonitis in peritoneal dialysis patients--absence of
      endotoxin in dialysate.
AB  - BACKGROUND: Indiscriminate use of broad-spectrum antibiotics in peritonitis may
      have either unwanted side effects or contribute to the development of antibiotic
      resistance. It is tempting to use broad-spectrum antibiotics in cases of culture
      negative peritonitis. This study examines whether Gram-negative agents have to be
      considered in the management of culture-negative peritonitis. Gram-negative
      agents are manifested by endotoxin easily detected by the Limulus amebocyte
      lysate (LAL) test. METHODS: 138 episodes of Gram-negative and culture-negative
      peritonitis have been retrospectively analyzed; episodes of Gram-negative
      peritonitis were controls. Correlation between LAL and culture results was
      compared between the two groups. The LAL test was performed using a commercial
      kit by incubating a mixture of dialysate effluent and LAL reagent at 37 degrees
      C. Development of a stable solid clot was considered positive. RESULTS: In
      controls, 80 out of 117 Gram-negative peritonitis were LAL positive (68%). None
      of the 21 culture-negative episodes was LAL positive. In 7 recurrences of Gram
      negative peritonitis, the LAL test turned from negative to positive but in none
      of the recurrences of culture-negative peritonitis. The difference in correlation
      was highly significant. CONCLUSIONS: Gram-negative organisms do not seem to be
      involved in sporadic culture-negative peritonitis. In episodes of peritonitis in
      which bacteriologic cultures stay negative for 48 h, initial coverage of Gram
      negative organisms may be dropped.

PMID- 18059112
TI  - Depression subtypes in bipolar I and II disorders.
AB  - BACKGROUND: Depression is the predominant mood alteration in bipolar I and II
      disorders. In this study, the nature of major depressive episodes of bipolar I
      versus bipolar II patients is specifically assessed, as regards lifetime history
      of rapid cycling, melancholia, atypical and psychotic symptoms. METHODS: The
      patient sample consisted of 184 bipolar I and 80 bipolar II patients, according
      to the research diagnostic criteria, who entered the bipolar disorders program in
      our hospital. Subsets of patients are compared according to DSM-IV criteria for
      rapid cycling, melancholic, atypical and psychotic features. RESULTS: Bipolar I
      patients had significantly more psychotic symptoms in their lifetime histories (p
      < 0.001), whereas bipolar II patients had significantly more atypical symptoms in
      their lifetime histories (p < 0.003). Although melancholia was more prevalent in
      the bipolar I and rapid cycling was more prevalent in the bipolar II subgroup,
      these differences did not reach statistical significance. CONCLUSIONS: The
      results of the study suggest that marked differences exist in the nature of major
      depressive episodes between bipolar I and II patients, as they in the long term
      emerge from the two conditions. To what extent both conditions are related cannot
      be ascertained in the present study. Clinical differences may have relevant
      therapeutic implications and separate trials for bipolar I and bipolar II
      depression are warranted.

PMID- 18059113
TI  - One-year outcome and its prediction in first-episode schizophrenia--a
      naturalistic study.
AB  - BACKGROUND: The literature suggests that the early course of schizophrenia is a
      strong predictor of long-term outcome. We sought to test this notion in a sample
      of first-episode patients. SAMPLING AND METHODS: Forty patients with a first
      episode of DSM-IV diagnoses of schizophrenia, schizoaffective, or
      schizophreniform disorder were assessed with well-established instruments such as
      the Positive and Negative Syndrome Scale and the Strauss-Carpenter Scale.
      Reassessment was performed 14 months later and included the Global Assessment of
      Functioning Scale in addition to the aforementioned instruments and a psychiatric
      interview. Regression analyses for the Global Assessment of Functioning Scale and
      symptomatology were used to identify outcome predictors. RESULTS: At follow-up,
      27 patients (67.5%) were in remission. Women's outcome was significantly better
      with respect to intimate relationships and domiciliary independence. Although
      symptomatology of the whole group remained stable during the follow-up period, a
      subgroup of patients experienced a significant decrease in symptom levels whereas
      symptoms increased in another subgroup. The most important predictor of outcome
      was compliance with atypical antipsychotic medication during the follow-up
      period. CONCLUSIONS: These results suggest that there is a prognostic divide
      early in the course of the disease, that compliance with medication is of
      overriding importance towards 1-year outcome, and that for the individual patient
      the question of chronicity may be answered very early in the course of the
      disease.

PMID- 18059114
TI  - Parental concordance and offspring risk for anxiety, conduct, depressive, and
      substance use disorders.
AB  - BACKGROUND: Although parental concordance for any psychiatric disorder is known
      to be associated with elevated risk for offspring disorder, little evidence is
      currently available from prospective longitudinal studies regarding the
      association of parental concordance with offspring risk for anxiety, conduct,
      depressive, and substance use disorders. SAMPLING AND METHODS: Psychiatric
      interviews were conducted with 593 mothers and their biological offspring at mean
      offspring ages 14, 16, 22, and 33. RESULTS: Offspring risk for >or=1 psychiatric
      disorder was significantly greater if both parents had a lifetime history of
      psychiatric disorder than if only one parent had a lifetime history of disorder.
      Parental concordance for generalized anxiety disorder (GAD) was associated with a
      significant increase in offspring risk for anxiety disorders, above and beyond
      the risk attributable to having one affected parent. In addition, parental
      concordance for GAD was associated with elevated risk for offspring depressive
      disorders, and parental concordance for substance use disorders was associated
      with elevated offspring risk for conduct disorder. CONCLUSIONS: Parental
      concordance for GAD may be associated with elevated risk for offspring anxiety
      disorder, above and beyond the risk associated with having one affected parent.

PMID- 18059115
TI  - Obsessive-compulsive disorder and posttraumatic stress disorder.
AB  - BACKGROUND: Previous studies suggested an association between exposure to trauma
      or stressful life events and obsessive-compulsive disorder (OCD). This study
      investigates the hypothesis that traumatic events and posttraumatic stress
      disorders (PTSD) precede the onset of OCD. SAMPLING AND METHODS: 210 cases with
      OCD from university treatment facilities were compared with 133 sex- and age
      matched controls from the adult general population. The data were derived from a
      German family study on OCD (GENOS). Direct interviews were carried out with the
      German version of the Schedule for Affective Disorders and Schizophrenia -
      Lifetime Version for Anxiety Disorders (DSM-IV). RESULTS: Severe traumatization
      occurred in 6.2% of the OCD cases and in 8.3% of the controls. The lifetime
      prevalence rates of traumatization, PTSD and acute stress disorder were not
      different between the subjects with OCD and controls (p > 0.05). In 6 cases,
      acute stress disorder, subclinical or full PTSD preceded the onset of OCD, in 3
      cases the trauma-related disorders and OCD occurred within the same year, in 5
      other cases, the trauma-related disorders started after the onset of OCD.
      CONCLUSION: There is no significant association of traumatization or PTSD with
      OCD compared with controls. Given the low rate of trauma-related disorders
      occurring before (2.9%) or within (1.5%) the same year as the onset of OCD other
      factors than severe traumatic events determine the onset of OCD in most of the
      cases.

PMID- 18059116
TI  - Severe neonatal pulmonary hypertension secondary to antenatal maternal diclofenac
      ingestion reversed by inhaled nitric oxide and oral sildenafil.

PMID- 18059118
TI  - Barium meal followthrough and CT findings in paraduodenal hernia.

PMID- 18059117
TI  - Clinicopathologic features of hepatic neoplasms in explanted livers: a single
      institution experience.
AB  - BACKGROUND: Hepatic neoplasms can be the primary indication for hepatic
      transplantation. The tumors can also be incidentally identified in explanted
      livers. We explored the clinicopathologic features of hepatic neoplasms
      identified in explanted livers. MATERIALS AND METHODS: All explanted livers
      resected between 2001 and 2006 were evaluated for the presence of neoplasms and
      their clinicopathologic features were examined. RESULTS: In 98 liver transplants,
      15 neoplasms (15.3%) were identified. Patient ages ranged from 5 to 63 years
      (median, 56 years). The primary etiology of hepatic disease was hepatitis C virus
      in 12 cases, hepatitis B virus in 1 case, cryptigenic cirrhosis in 1 case and
      congenital hepatic fibrosis in 1 case. Serum alpha-fetoprotein was significantly
      elevated (>400 U/L) in only 2 cases. CA19-9 was not elevated in any of the cases.
      The tumors included hepatocellular carcinoma (HCC) in 13 cases, 1 case of
      choloangiocarcinoma and 1 case of combined HCC and hepatoblastoma. The tumors in
      size from 0.5 to 5 cm (median 1.4 cm) and were multifocal in 5 of the cases
      (33%). Tissue alpha-fetoprotein expression was only seen in the cases associated
      with elevated serum levels. CONCLUSION: In our institution hepatic neoplasms are
      seen in more than 15% explanted livers. They can be incidentally indentified, are
      frequently not associated with elevated serum levels of alpha-fetoprotein and
      CA19-9, are commonly multifocal but small, and are associated with good
      prgonosis. Elevated serum alpha-fetoprotein, albeit specific, is not a very
      sensitive marker in the detection of hepatic neoplasms.

PMID- 18059119
TI  - Overweight and obesity among attendees of primary care clinics in a university
      hospital.

PMID- 18059120
TI  - Symptomatic congenital heart disease in the Saudi Children and Adolescents
      Project.

PMID- 18059121
TI  - Predictors of obstructive sleep apnea in snorers.
AB  - BACKGROUND: Snoring is a commong problem that poses a high risk for obstructive
      sleep apnea (OSA). We studied the contribution of risk factors for OSA in snorers
      for full-night polysomnography (PSG). METHODS: A questionnaire was administered
      to subjects referred for PSG in the period from April 2002 to March 2005.
      RESULTS: There were 191 (84%) snorers identified by 227 PSG studies. They had a
      mean age of 48.1+/-9.8 years, (age range, 23-73 years) and 78.5% were males. OSA
      as indicated by a respiratory disturbance index (RDI) of >5 events/hour was seen
      in 126 (66%) subjects. In males, 72.7% had OSA, with a mean RDI of 43.0+/-26
      events/hour, versus 41.5% [corrected] with OSA in females with a mean RDI of
      27.8+/-26.5 events/hour (P<0.001). The OSA group had a higher mean Epworth
      Sleepiness Scale (ESS) (P<0.001), a larger mean neck circumference (P<0.01), an
      increased mean age (P<0.050), and more witnessed apneas (P<0.001) but not choking
      (P=0.096). The mean increase in body mass index was linked to OSA only in females
      (P<0.05) but not in the overall study (P=0.507). Multivariate analysis showed
      that ESS, male gender, and a history of witnessed apneas were associated with
      OSA, while controlling for obesity, large neck circumference, age, and history of
      choking. CONCLUSION: In screening snorers for PSG, male gender, ESS and a history
      of witnessed apneas were the most important predictors of OSA, but other factors
      should be considered in referring snorers for PSG. In males, obesity did not
      contribute to the risk of OSA in our study population.

PMID- 18059122
TI  - The role of vitamin E in the prevention of cancer: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: There are conflicting results in published randomized controlled
      trials (RCTs) on the role of vitamin E in the prevention of cancer. We conducted
      a meta-analysis of RCTs to evaluate the role of vitamin E in the prevention of
      cancer in adults. METHODS: We included RCTs in which the outcomes of the intake
      of vitamin E supplement alone or with other supplements were compared to a
      control group. The primary outcomes were total mortality, cancer mortality, total
      incidence of cancer, and incidence of lung, stomach, esophageal, pancreatic,
      prostate, breast and thyroid cancers. All identified trials were reviewed
      independently by the two reviewers to determine whether trials should be included
      or excluded. The quality of all included studies was scored independently by the
      two reviewers. RESULTS: Twelve studies, which included 167025 participants, met
      the inclusion criteria. There were no statistically significant differences in
      total mortality (relative risk, 0.99; 95% CI, 0.96-1.03) among the different
      groups of patients included in this meta-analysis. Vitamin E was associated with
      a significant reduction in the incidence of prostate cancer (relative risk, 0.85;
      95% CI, 0.73-0.96, number needed to treat=500), but it did not reduce the
      incidence of any other types of cancer. CONCLUSIONS: Vitamin E supplementation
      was not associated with a reduction in total mortality, cancer incidence, or
      cancer mortality, but it was associated with a statistically significant
      reduction in the incidence of prostate cancer. Vitamin E can be used in the
      prevention of prostate cancer in men who are at high risk of prostate cancer.

PMID- 18059123
TI  - Bone mineral density in children wth systemic lupus erythematosus and juvenile
      rheumatoid arthritis.
AB  - BACKGROUND: Although there is increasing in bone metabolism in patients with
      rheumatic disorders, few data exist on bone mineral density (BMD) in children
      with rheumatic disorders or on the association of BMD with disease-related
      variables. We determined BMD in Iranian children with systemic lupus
      erythematosus (SLE) and juvenile rheumatoid arthritis (JRA) to evaluate the
      relationship between disease-related variables and BMD. PATIENTS AND METHODS:
      Twenty patients (13 girls and 7 boys) with SLE (n=15) and JRA (n=5) with a mean
      age of 13.10+/-3.29 years (range, 6-17 years), attending a pediatric rheumatology
      clinic and 20 healthy controls (matched for age and sex with each patient) were
      enrolled in a cross-sectional study between 2001 and 2003. BMD (g/cm(2)) of the
      femoral neck (BMD-F) and lumbar vertebrae (BMD-L) were measured by dual energy X
      ray absorptiometry (DEXA). The correlation between BMD and cumulative dose of
      steroids, daily dose of steroid, disease duration, disease activity, height,
      weight, and age was investigated. RESULTS: BMD in the patients (BMD-F=0.72+/
      0.15, BMD-L=0.70+/-0.19) was significantly lower than controls (BMD-F=0.95+/
      0.17, BMD-L=0.98+/-0.20, P=<0.001). The severity of descreased BMD was more
      prominent in lumbar vertebrae than the femoral neck (P=0.04). None of the
      variables were consistently related to a decrease in BMD. CONCLUSION: BMD was
      significantly lower in patients compared with controls. It was more prominent in
      lumbar vertebrae (trabecular bone). Although cumulative dose of steroids and
      diseaese appeared to have some influence on BMD, none were independently
      correlated with BMD.

PMID- 18059124
TI  - The prevalence and degree of resistance of Plasmodium falciparum to first-line
      antimalarial drugs: an in vitro study from a malaria endemic region in Yemen.
AB  - BACKGROUND: Unpublished studies on antimalarial drug efficacy have found low
      levels of chloroquine resistance in Yemen. This study was carried out to
      determine the current prevalence of drug resistance in Plasmodium falciparum in
      Yemen to the main anti-malarial drugs and to determine the effective
      concentration(EC) values. METHODS: The WHO standard protocol was used for the
      selection of subjects, collection of blood samples, culture techniques,
      examination of post-culture blood slides and interpretation of results. The in
      vitro micro-test Mark III was used for assessing susceptibility of P. falciparum
      isolates. RESULTS: The criteria for blood parasite density was met by 219 P.
      falciparum malaria patients. Chloroquine resistance was found in 47% of isolated
      P. falciparum schizonts. Mefloquine resistanfce was found in 5.2%. In addition,
      the EC50 and EC95 values in blood that inhibited schizont maturation in resistant
      isolates were higher than the normal therapeutic level of mefloquine. No
      resistance occurred against quinine or artemisinin, with no growth at hte cut-off
      level of quinine and inhibition of low concentrations of artemisinin. CONCLUSION:
      Our study confirmed the occurrence of chloroquine-resistant P. falciparum and a
      slow increase in the rate of this resistance; it is likely that resistance will
      increase further and spread over all the foci of malaria in Yemen. The low rate
      of mefloquine-resistant P. falciparum, was lower than that reported in Africa or
      Southeast Asia, but it is the first report of mefloquine resistance in Yemen.
      Finally, the isolates were sensitive to low-concentrations of quinine and
      artemisinin.

PMID- 18059125
TI  - Preoperative nutritional parameters in children with congenital heart diseases
      under two years of age.

PMID- 18059126
TI  - Probable montelukast-induced hepatotoxicity in a pediatric patient: case report.

PMID- 18059127
TI  - Pemphigus vulgaris in a neonate.

PMID- 18059129
TI  - Cochlear implantation in Bahrain: promising results.

PMID- 18059128
TI  - Comparison of gated SPECT, echocardiography and cardiac magnetic resonance
      imaging for the assessment of left ventricular ejection fraction and volumes.
AB  - BACKGROUND: Left ventricular ejection fraction (LVEF), end-diastolic volume (EDV)
      and end-systolic volume (ESV) can be determined non-invasively by two-dimensional
      enchocardiography (ECHO), gated sinle photon emission computed tomography
      (GSPECT) and cardiac magnetic resonance imaging (CMRI). This study was designed
      to analyze the concordance between LVEF, EDV and ESV values derived from ECHO,
      GSPECT and CMRI. METHODS: ECHO, GSPECT and CMRI were performed in a group of 21
      patients with suspected coronary artery disease. LVEF, EDV and ESV values were
      calculated. RESULTS: The mean LVEF measured with GSPECT, ECHO and CMRI were
      55.9+/-17.8%, 55.7+/-16.4% and 56.4+/-15.7%, respectively. The mean EDV measured
      with GSPECT, ECHO and CMRI were 109.2+/-42.45 mL, 127.5+/-42.2 mL, 91.1+/-38.0
      mL, respectively. The mean ESV measured with GSPECT, ECHO and CMRI were 54.2+/
      41.2 mL, 59.9+/-37.6 mL and 41.8+/-26.9 mL, respectively. The results of linear
      regression analysis showed very good correlation between LVEF and ESV values
      derived from GSPECT, ECHO adn CMRI (r=0.91, r=0.92, r=0.97 for LVEF and r=0.86,
      r=0-91, r=0.91 for ESV, P<0.01). Good correlations were found between EDV values
      obtained from GSPECT, ECHO and CMRI (r=0.71, r=0.68, r=0.73, P<0.01). Agreement
      between these techniques in LVEF values was also good, but not in LV volumes,
      according to Bland-Altman plots. CONCLUSIONS: This study showed good overall
      correlations between LVEF, EDV and ESV values derived from GSPECT, ECHO and CMRI.
      LVEF obtained from any of these three imaging modalities could be used
      interchangeably. However, care should be taken in comparing LV volumes.

PMID- 18059130
TI  - Multidrug resistant Acinetobacter nosocomial meningitis treated successfully with
      parenteral tigecycline.

PMID- 18059131
TI  - Ibn Al-Haytham: father of modern optics.

PMID- 18059132
TI  - WNKs: protein kinases with a unique kinase domain.
AB  - WNKs (with-no-lysine [K]) are a family of serine-threonine protein kinases with
      an atypical placement of the catalytic lysine relative to all other protein
      kinases. The roles of WNK kinases in regulating ion transport were first revealed
      by the findings that mutations of two members cause a genetic hypertension and
      hyperkalemia syndrome. More recent studies suggest that WNKs are pleiotropic
      protein kinases with important roles in many cell processes in addition to ion
      transport. Here, we review roles of WNK kinases in the regulation of ion balance,
      cell signaling, survival, and proliferation, and embryonic organ development.

PMID- 18059133
TI  - Calcium-influx increases SOD1 aggregates via nitric oxide in cultured motor
      neurons.
AB  - Familial amyotrophic lateral sclerosis (fALS) is caused by mutations in Cu/Zn
      superoxide dismutase (SOD1), and SOD1 aggregation and calcium toxicity are
      involved in neuronal death. However, the effect of altered calcium homeostasis on
      the SOD1 aggregation is unknown. To investigate whether calcium triggers mutant
      SOD1 aggregation in vitro, human mutant SOD1 (G93A) was transfected into motor
      neuronal cell line (VSC 4.1 cells). These cells were then treated with calcium
      ionophore A23187 or agents that induce intracellular calcium release like cyclic
      ADP ribose, ryanodine or thapsigargin. A23187 was found to increase mutant SOD1
      aggregation and neuronal nitric oxide synthase (nNOS) expression. Moreover, the
      NOS inhibitor (L-NAME) and a NO-dependent cyclic GMP cascade inhibitor (ODQ)
      reduced SOD1 aggregation, whereas an exogenous NO donor (GSNO) increased mutant
      SOD1 aggregation, which was also prevented by NOS or cGMP cascade inhibitor. Our
      data demonstrate that calcium-influx increases SOD1 aggregation by upregulating
      NO in cultured motor neuronal cells.

PMID- 18059134
TI  - Inhibition of gamma ray-induced apoptosis by stimulatory heterotrimeric GTP
      binding protein involves Bcl-xL down-regulation in SH-SY5Y human neuroblastoma
      cells.
AB  - Heterotrimeric GTP-binding proteins (G proteins) transduce extracellular signals
      into intracellular signals by activating effector molecules including adenylate
      cyclases that catalyze cAMP formation, and thus regulate various cellular
      responses such as metabolism, proliferation, and apoptosis. cAMP signaling
      pathways have been reported to protect cells from ionizing radiation-induced
      apoptosis, but however, the protective mechanism is not clear. Therefore, this
      study aimed to investigate the signaling molecules and the mechanism mediating
      the anti-apoptotic action of cAMP signaling system in radiation-induced
      apoptosis. Stable expression of a constitutively active mutant of Gas (GalphasQL)
      protected gamma ray-induced apoptosis which was assessed by analysis of the
      cleavages of PARP, caspase-9, and caspase-3 and cytochrome C release in SH-SY5Y
      human neuroblastoma cells. GasQL repressed the gamma ray-induced down-regulation
      of Bcl-xL protein, but transfection of Bcl-xL siRNA increased the gamma ray
      induced apoptosis and abolished the anti-apoptotic effect of GasQL. GasQL
      decreased the degradation rate of Bcl-xL protein, and it also restrained the
      decrease in Bcl-xL mRNA by increasing the stability following ionizing
      irradiation. Furthermore, prostaglandin E2 that activates Gas was found to
      protect gamma ray-induced apoptosis, and the protective effect was abolished by
      treatment with prostanoid receptor antagonist specific to EP2/4R subtype.
      Moreover, specific agonists for adenosine A1 receptor that inhibits cAMP
      signaling pathway augmented gamma ray-induced apoptosis. From this study, it is
      concluded that Galphas-cAMP signaling system can protect SH-SY5Y cells from gamma
      ray-induced apoptosis partly by restraining down-regulation of Bcl-xL expression,
      suggesting that radiation-induced apoptosis can be modulated by GPCR ligands to
      improve the efficiency of radiation therapy.

PMID- 18059135
TI  - Homo-dimerization of RyR1 C-terminus via charged residues in random coils or in
      an alpha-helix.
AB  - To investigate the mechanism by which the C-terminus (4,938-5,037) of the
      ryanodine receptor 1 (RyR1) homo-tetramerizes, forming a functional Ca(2+)
      release channel, the structural requirements for the tetramerization were studied
      using site-directed mutagenesis. Alanine-substitutions at five charged residues,
      E4976, H5003, D5026, E5033 and D5034, significantly decreased the formation of
      homo-dimers (reduced by >50%). Interaction between the C-terminus and cytoplasmic
      loop I (4,821-4,835) required two positively charged residues, H4832 and K4835.
      Based on the predicted protein secondary structures, all seven charged residues
      are located in random coils. Paired alanine-substitutions at six negatively
      charged residues (E4942A/D4953A, D4945A/E4952A and E4948A/ E4955A) of the alpha
      helix (4,940-4,956) in the C-terminus increased homo-dimerization. Therefore, the
      homo-tetramerization of RyR1 may be mediated by intra- and/or inter-monomer
      electrostatic interactions among the C-terminal charged residues in random coils
      or in an alpha-helix.

PMID- 18059136
TI  - Bee venom stimulates human melanocyte proliferation, melanogenesis, dendricity
      and migration.
AB  - Pigmentation may result from melanocyte proliferation, melanogenesis, migration
      or increases in dendricity. Recently, it has been reported that secreted
      phospholipase A(2)(sPLA(2)) known as a component of bee venom (BV), stimulates
      melanocyte dendricity and pigmentation. BV has been used clinically to control
      rheumatoid arthritis and to ameliorate pain via its anti-inflammatory and
      antinociceptive properties. Moreover, after treatment with BV, pigmentation
      around the injection sites was occasionally observed and the pigmentation lasted
      a few months. However, no study has been done about the effect of BV on
      melanocytes. Thus, in the present study, we examined the effect of BV on the
      proliferation, melanogenesis, dendricity and migration in normal human
      melanocytes and its signal transduction. BV increased the number of melanocytes
      dose and time dependently through PKA, ERK, and PI3K/Akt activation. The level of
      cAMP was also increased by BV treatment. Moreover, BV induced melanogenesis
      through increased tyrosinase expression. Furthermore, BV induced melanocyte
      dendricity and migration through PLA(2) activation. Overall, in this study, we
      demonstrated that BV may have an effect on the melanocyte proliferation,
      melanogenesis, dendricity and migration through complex signaling pathways in
      vitro, responsible for the pigmentation. Thus, our study suggests a possibility
      that BV may be developed as a therapeutic drug for inducing repigmentation in
      vitiligo skin.

PMID- 18059137
TI  - Effect of bosentan on the production of proinflammatory cytokines in a rat model
      of emphysema.
AB  - Endothelin (ET) receptor antagonists have been developed to produce a reduction
      of ET related effects in various diseases, as well as in animal models of airway
      inflammation. We aimed to investigate the anti-inflammatory potential of bosentan
      on a rat model of emphysema. Thirty Wistar male rats were classified as control
      group (group 1), intratracheally (i.t.) instilled with saline, treated with
      vehicle solution; elastase group (group 2), i.t. instilled with porcine
      pancreatic elastase (PPE), treated with vehicle solution; and PPE+bosentan group
      (group 3), i.t. instilled with PPE, treated with bosentan. The levels of TNF
      alpha, IL-1beta, IL-6, and IL-8 in bronchoalveolar lavage fluid (BALF) and lung
      tissue, cell counts in BALF, and histologic analysis of all groups were
      evaluated. Neutrophile granulocytes (NG) and alveolar macrophages (AM) were
      increased more in group 2 than in group 1 (P<0.001, P=0.04, respectively).
      Compared with group 2, neutrophil granulocyte (NG) and alveolar macrophages (AM)
      counts were decreased in group 3 (P<0.001). Histological examination confirmed a
      diffuse neutrophilic inflammation and irregular alveolar air space enlargement in
      group 2. Treatment with bosentan partially reduced the enlarged lung volumes.
      Compared with group 1, the BALF levels of TNF-alpha and IL-6, and the lung tissue
      levels of IL-1beta, IL-6, and IL-8 were increased in group 2 (P=0.028, P=0.005,
      P=0.001, P=0.019, P<0.001, respectively). The TNF-alpha and IL-8 levels of BALF
      (P=0.007, P=0.001, respectively), and the TNF-alpha, IL-1beta, IL-6, and the IL-8
      levels of lung tissue (P=0.031, P=0.017, P=0.007, P<0.001) were decreased in
      group 3 compared to group 2. In conclusion, bosentan decreased the inflammatory
      response by reducing numbers of inflammatory cells and proinflammatory cytokines.

PMID- 18059138
TI  - Immunocytochemical detection of HPV16 E7 in cervical smear.
AB  - Cervical cancer is characterized by a long period of preclinical dysplasia or
      carcinoma in situ progressing into invasive cancer. Although Papanicolaou (Pap)
      smear test has contributed significantly to the early detection of precursor
      lesions, the cytological screening has inherent problems that produce
      considerable false negative/positive results. Since the infection of high-risk
      type of human papillomavirus (HPV) is strongly associated with cervical cancer,
      we investigated the feasibility of an immunostaining test to detect cells
      infected by HPV in cervical smear. We produced monoclonal antibodies against
      HPV16 E7 in mice by repeated injections with the recombinant HPV16 E7. Western
      blot analysis and immunocytochemical assay demonstrated that the selected
      monoclonal antibody, mAb (130-9-7), reacts specifically with cultured cervical
      cancer cell lines infected by HPV16. Specific staining was observable with the
      HPV16-positive smear specimens obtained from the cervical cancer patients,
      whereas no staining was detected with the HPV-negative smear specimens. To
      achieve the desired sensitivity, specificity and reproducibility, we modified and
      optimized the conventional immunocytochemical procedure for cervical smear
      specimens. Our results suggest that this immunostaining method for detecting high
      risk HPV in cervical smear may be used as a strategy to distinguish a high-risk
      group, especially those patients with low grade cytological abnormality.

PMID- 18059139
TI  - Change of connexin 37 in allergen-induced airway inflammation.
AB  - Gap junction channels formed with connexins directly link to the cytoplasm of
      adjacent cells and have been implicated in intercellular signaling. Connexin 37
      (Cx37) is expressed in the gas-exchange region of the lung. Recently, Cx37 has
      been reported to be involved in the pathogenesis of inflammatory disease.
      However, no data are available on the role of Cx37 in allergic airway
      inflammatory disease. In the present study, we used a murine model of ovalbumin
      (OVA)- induced allergic airway disease and primary murine epithelial cells to
      examine the change of Cx37 in allergic airway disease. These mice develop the
      following typical pathophysiological features of asthma: airway
      hyperresponsiveness, airway inflammation, and increased IL-4, IL-5, IL-13,
      intercellular adhesion molecule-1, vascular cell adhesion molecule-1, eotaxin,
      and RANTES levels in lungs. Cx37 protein and mRNA expression were decreased in
      OVA-induced allergic airway disease. Immunoreactive Cx37 localized in epithelial
      layers around the bronchioles in control mice, which dramatically disappeared in
      allergen-induced asthmatic lungs. Moreover, the levels of Cx37 protein in lung
      tissues showed significantly negative correlations with airway inflammation,
      airway responsiveness, and levels of Th2 cytokines in lungs. These findings
      indicate that change of Cx37 may be associated with the asthma phenotype.

PMID- 18059140
TI  - Identification of molecular markers for the oncogenic differentiation of
      hepatocellular carcinoma.
AB  - The aim of this study was to identify molecular markers associated with oncogenic
      differentiation in hepatocellular carcinoma (HCC). Using an unsupervised
      clustering method with a cDNA microarray, HCC (T) gene expression profiles and
      corresponding non-tumor tissues (NT) from 40 patients were analyzed. Of total 217
      genes, 72 were expressed preferentially in HCC tissues. Among 186 differentially
      regulated genes, there were molecular chaperone and tumor suppressor gene
      clusters in the Edmondson grades I and II (GI/II) subclass compared with the
      liver cirrhosis (LC) subclass. The Edmondson grades III and IV (GIII/IV) subclass
      with a poor survival (P=0.0133) contained 122 differentially regulated genes with
      a cluster containing various metastasis- and invasion-related genes compared with
      the GI/II subclass. Immunohistochemical analysis revealed that ANXA2, one of the
      72 genes preferentially expressed in HCC, was over-expressed in the sinusoidal
      endothelium and in malignant hepatocytes in HCC. The genes identified in the HCC
      subclasses will be useful molecular markers for the genesis and progression of
      HCC. In addition, ANXA2 might be a novel marker for tumor angiogenesis in HCC.

PMID- 18059141
TI  - Cardiac side population cells exhibit endothelial differentiation potential.
AB  - Recent studies have shown that side population (SP) cells, isolated from adult
      myocardium, represent a distinct cardiac progenitor cell population that exhibits
      functional cardiomyogenic differentiation. However, information on the intrinsic
      characteristics and endothelial potential, of cardiac SP cells, is limited. The
      present study was designed to investigate whether cardiac SP cells exhibit
      endothelial differentiation potential. The cardiac SP cells more highly expressed
      the early cardiac transcription factors as well as endothelial cell markers
      compared to the bone marrow-SP cells. After treatment with VEGF, for 28 days,
      cardiac SP cells were able to differentiate into endothelial cells expressing von
      Willebrand factor as determined by immunocytochemistry. Furthermore, expression
      of endothelial cell markers increased several-fold in VEGF-treated cardiac SP
      cells compared to the control group when assessed by real-time PCR. We also
      confirmed that cardiac SP cells provided a significantly augmented ratio of
      ischemic/normal blood flow, in the cardiac SP cell-transplanted group compared
      with saline-treated controls on postoperative days 7, 14, 21 and 28, in a murine
      model. These results show that cardiac SP cells may contribute to regeneration of
      injured heart tissues partly by transdifferentiation into angiogenic lineages.

PMID- 18059142
TI  - Recombinant tetra-cell adhesion motifs supports adhesion, migration and
      proliferation of keratinocytes/fibroblasts, and promotes wound healing.
AB  - An extracellular matrix protein plays an important role in skin wound healing. In
      the present study, we engineered a recombinant protein encompassing the 9(th) and
      10(th) type III domains of fibronectin, and 4(th) FAS1 domain of betaig-h3. This
      recombinant protein, in total, harbors four known-cell adhesion motifs for
      integrins: Pro-His-Ser-Arg-Asn (PHSRN) and Arg-Gly-Asp (RGD) in 9(th) and 10(th)
      type III domains of fibronectin, respectively, and Glu-Pro-Asp-Ile-Met (EPDIM)
      and Try-His (YH) in 4(th) FAS1 domain of betaig-h3, were designated to tetra-cell
      adhesion motifs (T-CAM). In vitro studies showed T-CAM supporting adhesion,
      migration and proliferation of different cell types including keratinocytes and
      fibroblasts. In an animal model of full-thickness skin wound, T-CAM exhibited
      excellent wound healing effects, superior to both 4(th) FAS1 domain of betaig-h3
      or 9(th) and 10(th) type III domains of fibronectin. Based on these results, T
      CAM can be applied where enhancement of cell adhesion, migration and
      proliferation are desired, and it could be developed into novel wound healing
      drug.

PMID- 18059143
TI  - Low-density lipoprotein protects Vibrio vulnificus-induced lethality through
      blocking lipopolysaccharide action.
AB  - Lipoprotein plays a role in the host defense against bacterial infection, and its
      serum level has been demonstrated to be an important prognosis factor of
      survival. We have previously demonstrated that LDL directly inactivates the
      hemolytic activity of Vibrio vulnificus cytolysin (VVC) in vitro. The object of
      this study was therefore to examine whether the LDL-mediated inactivation of VVC
      leads to protection against lethal infection of V. vulnificus in vivo, using wild
      and VVC-deficient V. vulnificus strains. Unexpectedly, we found that LDL protects
      mouse lethality induced by VVC-deficient as well as wild V. vulnificus strain. We
      also demonstrated that LDL blocks V. vulnificus LPS-induced lethality in mice.
      These results suggest that LDL preferentially act on endotoxin rather than
      exotoxin in the protection against V. vulnificus-induced mice lethality.

PMID- 18059144
TI  - [Judicial judgment for severe adverse drug reaction (ADR)].

PMID- 18059145
TI  - [Drug-induced hypersensitivity syndrome: DIHS].

PMID- 18059146
TI  - [Improvement of quality of medical research and practice in allergology].

PMID- 18059147
TI  - [Medical practice in allergic diseases in the present Japanese medical health
      care system from the aspect of medical sociology].

PMID- 18059148
TI  - [Diagnosis and treatment of allergic rhinitis].

PMID- 18059149
TI  - [Influence of the difference in the pollen count on medical costs in an allergen
      specific immunotherapy for Japanese cedar pollinosis].
AB  - BACKGROUND: We studied medical economic efficacy and influence by the different
      number of pollen scattering in patients treated with allergen-specific
      immunotherapy for Japanese cedar pollinosis. METHODS: We calculated medical
      treatment costs and the medicine expense from medical records in eighteen cedar
      pollinosis patients treated with allergen-specific immunotherapy (IT-G) and with
      medications (M-G). We examined with the same patients for three years of
      different pollen scattering, mass scattering year (2005), moderate scattering
      year (2003), a few scattering year (2004). Furthermore, satisfaction of treatment
      and symptom score measured by visual analog scale in both subjects was studied in
      a mass scattering year. RESULTS: Total medical costs at hospital was cheaper in
      IT-G than in M-G. The result was depended on prescribed medical costs. In
      addition, prescribed medicine agents and total medical costs did not increase by
      the mass scattering year of pollen. Satisfaction of treatment and symptom score
      in IT-G was better than that in M-G. CONCLUSION: Immunotherapy had a benefit on a
      medical economy.

PMID- 18059150
TI  - [Therapy with nebulized beta2 agonists (procaterol) in asthmatic children:
      pulmonary function and plasma levels after inhalation].
AB  - BACKGROUND: Relationship between post administrative changes in plasma drug
      levels and bronchodilation remains unknown. In this study, we measured plasma
      levels of procaterol, a beta2-agonist, when being inhaled through nebulizers in
      children with bronchial asthma to examine relationship between improvement of
      pulmonary function and the plasma levels. METHOD: Six asthmatic children with the
      mean age of 9.8 years, inhaled 0.3 ml of 0.01% procaterol solution through a
      nebulizer. We examined changes in pulmonary function and plasma procaterol levels
      before and after inhalation. RESULTS: Procaterol was detected in the plasma 2
      minutes after inhalation when it already rose to the maximum level, and kept the
      steady until showing a decline in 30 minutes. The measured highest value was
      87.8+/-45.1 pg/ml. FEV 1.0 remarkably increased 2 minutes after inhalation and
      was maintained until 60 minutes after inhalation. Other lung function parameters
      also improved. There was no significant change in the heart rate, but serum
      potassium concentrations significantly dropped in all patients 60 minutes after
      inhalation. CONCLUSION: Plasma procaterol levels promptly rose to the peak at 2
      minutes after inhalation and decreased 30 minutes later. Improvement of pulmonary
      function started promptly at minutes after inhalation and it became a peak 60
      minutes later.

PMID- 18059151
TI  - [Prevalence of chlamydia-pneumoniae-specific immunoglobulin M antibody and acute
      exacerbations of asthma in childhood].
AB  - BACKGROUND: Chlamydia pneumoniae is a frequent causative agent of acute
      respiratory disease and has been recently reported as a possible cause of asthma.
      We investigated the prevalence of C. pneumoniae infections in childhood patients
      with acute exacerbations of asthma. METHOD: One hundred twenty-six childhood
      patients with acute exacerbations of asthma, 77 with acute bronchitis and 22
      Respiratory syncytial virus infections were studied. Serum samples were obtained
      and tested for C. pneumoniae-specific IgM antibody by Enzyme-Linked ImmunoSorbent
      Assay (ELISA). RESULTS: C. pneumoniae IgM-positive results were observed in 48.4%
      (Index value>or=1.60) and 23% (Index value>or=1.10) of patients with acute
      exacerbations of asthma. The prevalence of C. pneumoniae-specific IgM was
      significantly higher in asthma cases than in other subjects (p<0.05). CONCLUSION:
      Our data suggest that C. pneumoniae infection may trigger acute exacerbations of
      childhood asthma.

PMID- 18059152
TI  - [Evaluation of the drug lymphocyte stimulation test (DLST) with shosaikoto].
AB  - BACKGROUND: Our aim is to evaluate the significance of DLST by Shosaikoto.
      METHODS: We clinically evaluated 3 cases of drug-induced pneumonia assumed to be
      caused by Shosaikoto, and we performed DLST of Shosaikoto for healthy controls,
      and compared the data with drug-induced pneumonia cases of Shosaikoto. RESULTS:
      As clinical characteristics of 3 cases, 2 cases were positive for hepatitis C
      virus antibody, and 1 case was positive for DLST of Shosaikoto. The observed
      chest high-resolution CT (HRCT) findings showed hypersensitivity pneumonia (HP)
      pattern in all 3 cases. Prognosis was good in all 3 cases. DLST of Shosaikoto was
      positive in 27.5% of healthy controls. Stimulation index (S.I.) of DLST in drug
      induced pneumonia cases increased depending on drug dilution density, compared to
      that of healthy controls. CONCLUSION: DLST of Shosaikoto showed high false
      positive rate. However, we may be able to distinguish the true-positive cases
      with the false-positive cases by comparing the S.I. of DLST according to drug
      dilution density.

PMID- 18059153
TI  - [Case of allergic bronchopulmonary aspergillosis successfully treated with
      itraconazole].
AB  - A 58-year-old woman had a productive cough but not from bronchial asthma. A chest
      radiograph revealed infiltrative shadows in right middlelung field on September,
      2004. Aspergillus fumigatus was detected in a sputum culture. She was treated
      with oral itraconazole. After the treatment, infiltrative shadows on her chest
      radiograph disappeared. On October 2005, her peripheral blood showed
      eosinophilla, a high serum level of total immunoglobulin E (IgE), and a chest
      radiograph revealed new infiltrative shadows in both lung fields. A chest
      computed tomography revealed multiple nodular shadows and central bronchiectasis.
      We detected a mucoid plug which showed a large number of eosinophils
      pathologically by bronchoscopy. Aspergillus niger was detected in a bronchial
      lavage fluid. We therefore made a diagnosis of allergic bronchopulmonary
      aspergillosis (ABPA). The decreases of peripheral blood eosinophils and a serum
      IgE level were recognized and multiple nodular shadows disappeared by
      reinstitution of itraconazole. However, a chest computed tomography revealed new
      infiltrative shadows. Therefore, we treated her with the concomitant
      administration of oral itraconazole and inhaled corticosteroid. All laboratory
      data and image findings were improved. It is critical to consider the both
      aspects of allergy and infection in the treatment for ABPA.

PMID- 18059154
TI  - [Type 1 allergy to formaldehyde in root canal sealant after dental treatment: two
      case reports and review of the literature].
AB  - Two cases of generalized urticaria after the dental treatment were reported.
      These cases had clearly positive RAST to formaldehyde, whereas skin prick
      testings were negative. We diagnosed them as type I allergy due to formaldehyde.
      Immediate type formaldehyde allergy is not widely recognized as a major allergic
      complication of dental treatment. Previous reports of immediate allergy to
      formaldehyde in dental treatment were reviewed. The characteristics are the
      followings, first, it tends to represent severe symptom like anaphylaxis, second,
      the symptom often appears a few hours later than usual cases of anaphylaxis.
      Allergen tests show highly positive ratio to formaldehyde RAST, whereas skin
      prick test often shows false negative. Assessment of specific IgE to formaldehyde
      is a useful and a diagnostic measurement, and is recommended in patients at risk.

PMID- 18059155
TI  - [Case of pollinosis to grass pollens who presented with dyspnea successfully
      treated by rush immunotherapy].
AB  - We present a 15 years old boy who experienced unusual symptoms for pollen
      allergy, and successfully treated by rush immunotherapy. The patient started to
      complain erythema and edema on his face and serous rhinorrhea at 10 years old
      when going out. He entered baseball team at junior high school, and subsequently
      experienced choking sensation, dyspnea, face edema, and it was sometimes
      impossible to continue play. He was diagnosed as bronchial asthma at some
      hospital, and prescribed many anti-asthma medications including inhaled
      corticosteroid, which did not take effect. His symptoms deteriorated in summer
      and ameliorated in winter. When he was 15 years old, he was referred to us by a
      pediatrician for reassessment of his symptoms. Flow-volume curve was normal, and
      bronchial provocation test (acetylcholine and histamine), and exercise challenge
      were negative. IgE antibodies specific to grass pollens were highly positive. We
      made a diagnosis of pollinosis to grass pollens instead of bronchial asthma. Oral
      antihistamines and intranasal corticosteroid partially improved his symptoms. We
      started rush-immunotherapy of grass-pollens (oats and bromegrass), Japanese
      cedar, and ragweed. His symptoms improved dramatically on the next season of
      grass pollens.

PMID- 18059156
TI  - [Influence of leukotriene receptor antagonists on prognosis of patients with
      bronchial asthma].

PMID- 18059157
TI  - Radiosensitization of prostate cancer by priming the wild-type p53-dependent
      cellular senescence pathway.
AB  - A dramatic stage-migration in diagnosis of prostate cancer has led to earlier
      detection of clinically localized carcinoma and an increased use of radiation
      therapy. The p53 protein responds to irradiation-induced DNA damage by removing
      critically damaged cells from the proliferative pool. This review will focus on
      the dominant role that p53-dependent cellular senescence, rather than cell death,
      plays in determining the radiosensitivity of human prostate cancer cells in
      vitro. The finding that senescence is a primary mechanism of tumor regression
      indicates that p53 activators or downstream effectors may prove effective in
      radiosensitizing some carcinoma of the prostate.

PMID- 18059158
TI  - BMP suppresses PTEN expression via RAS/ERK signaling.
AB  - Bone morphogenetic protein (BMP), a member of the transforming growth factor beta
      family, classically utilizes the SMAD signaling pathway for its growth
      suppressive effects,and loss of this signaling cascade may accelerate cell
      growth. In the colon cancer predisposition syndrome Juvenile Polyposis, as well
      as in the late progression stages of nonsyndromic colorectal cancers, SMAD4
      function is typically abrogated. Here, we utilized the SMAD4-null SW480 colon
      cancer cell line to examine BMPs effect on a potential target gene, PTEN, and how
      its expression might be regulated. Initial treatment of the SMAD4-null cells with
      BMP resulted in mild growth suppression, but with prolonged exposure to BMP, the
      cells become growth stimulatory, which coincided with observed decreases in
      transcription and translation of PTEN, and with corresponding increases in
      phospho-AKT protein levels. BMP-induced PTEN suppression was mediated via the
      RAS/ERK pathway, as pharmacologic inhibition of RAS/ERK, or interference with
      protein function in the cytosol by DN-RAS prevented BMP-induced growth promotion
      and changes in PTEN levels, as did treatment with noggin, a BMP ligand inhibitor.
      Thus, BMP downregulates PTEN via RAS/ERK in a SMAD4-null environment that
      contributes to cell growth, and constitutes a SMAD4-independent but BMP
      responsive signaling pathway.

PMID- 18059159
TI  - Signaling pathway of autophagy associated with innate immunity.
AB  - Autophagy has recently been shown to be an important component of the innate
      immune response. The signaling pathways leading to activation of autophagy in
      innate immunity are not well studied. Our recent study shows that Toll-like
      receptor 4 (TLR 4) serves as an environmental sensor for autophagy. We define a
      new molecular pathway in which lipopolysaccharide (LPS) induces autophagy in
      human and murine macrophages by a pathway regulated through Toll-interleukin 1
      receptor domain-containing adaptor-inducing interferon-beta (TRIF)-dependent,
      myeloid differentiation factor 88 (MyD88)-independent TLR4 signaling. Receptor
      interacting protein (RIP1) and p38 mitogen-activated protein-kinase (MAPK) are
      downstream components of this pathway. This signaling pathway does not affect
      cell viability, indicating that it is distinct from an autophagic death signaling
      pathway. We further show that LPS-induced autophagy can enhance mycobacterial co
      localization with the autophagosomes. The above study raises important questions.
      (1) What is the complete signaling pathway for LPS-induced autophagy? (2) Does
      TLR3 mediate autophagy? (3) What are the mechanisms that determine whether
      autophagy acts as a pro-death or pro-survival pathway? (4) What are the
      physiological functions of LPS-induced autophagosomes? Future studies examining
      the above questions should provide us with important clues as to how autophagy is
      regulated in innate immunity, and how autophagy can be utilized in pathogen
      clearance.

PMID- 18059160
TI  - Promoting basal levels of autophagy in the nervous system enhances longevity and
      oxidant resistance in adult Drosophila.
AB  - Autophagy is involved with the turnover of intracellular components and the
      management of stress responses. Genetic studies in mice have shown that
      suppression of neuronal autophagy can lead to the accumulation of protein
      aggregates and neurodegeneration. However, no study has shown that increasing
      autophagic gene expression can be beneficial to an aging nervous system. Here we
      demonstrate that expression of several autophagy genes is reduced in Drosophila
      neural tissues as a normal part of aging. The age-dependent suppression of
      autophagy occurs concomitantly with the accumulation of insoluble ubiquitinated
      proteins (IUP), a marker of neuronal aging and degeneration. Mutations in the
      Atg8a gene (autophagy-related 8a) result in reduced lifespan, IUP accumulation
      and increased sensitivity to oxidative stress. In contrast, enhanced Atg8a
      expression in older fly brains extends the average adult lifespan by 56% and
      promotes resistance to oxidative stress and the accumulation of ubiquitinated and
      oxidized proteins. These data indicate that genetic or age-dependent suppression
      of autophagy is closely associated with the buildup of cellular damage in neurons
      and a reduced lifespan, while maintaining the expression of a rate-limiting
      autophagy gene prevents the age-dependent accumulation of damage in neurons and
      promotes longevity.

PMID- 18059161
TI  - Green tea polyphenol and epigallocatechin gallate induce apoptosis and inhibit
      invasion in human breast cancer cells.
AB  - Currently, there is no effective therapy for estrogen independent breast cancer.
      MDA-MB-231 is an estrogen receptor negative highly invasive human breast cancer
      cell line and has been used as a relevant model system to evaluate drugs with
      chemopreventive potential against highly invasive breast cancer phenotypes.
      Epidemiological studies though inconclusive have shown that consumption of Green
      Tea Polyphenols (GTP) reduces the incidence and progression of breast cancer.
      Green tea is an important source of antioxidants that may be useful for
      chemoprevention of cancer. Recently published preclinical study from our lab
      suggested that GTP and EGCG treatment inhibit proliferation and induce apoptosis
      of MDA-MB-231. In this study, we have evaluated apoptotic and anti-invasive
      activity of green tea polyphenols (GTP) and its principal constituent
      Epigallocatechin gallate (EGCG) in MDA-MB-231 human breast cancer cell line. In
      in vitro human breast cancer model, EGCG and GTP induced apoptosis and
      significantly decreased invasion of breast cancer cells. Western blotting of MDA
      MB-231 cell lysates from EGCG and GTP treated and untreated control revealed an
      increase in bax, reduction in bcl2 and PARP cleavage. Quantitative fluorescence
      labeling resulted in a 24-28% reduction in invasion through matrigel by EGCG and
      15-23% reduction by GTP in a dose dependent manner. Focussed microarray analysis
      and reverse transcriptase polymerase chain reaction and zymogram analysis
      revealed inhibition of MMP-9 expression by polyphenol treatment. Furthermore, AKT
      was found to be inhibited both at the RNA and protein level by polyphenol
      treatment. Moreover EGCG and GTP decreased AKT phosphorylation as found out by
      Western blotting for Phospho-AKT (Ser-473). beta-catenin level was found to be
      decreased both in cytoplasm and nucleus. For the first time we report the
      connection of beta-catenin and AKT modulation by GTP and EGCG as a possible
      mechanism for the induction of apoptosis in human breast cancer cells and also
      inhibition in their invasive capacity.

PMID- 18059162
TI  - Regulation and pharmacokinetics of inducible recombinant TRAIL expression.
AB  - TRAIL is a potent antitumor agent, but its potential toxicity to normal human
      tissues limits its clinical applications in future. Therapy of human tumors might
      benefit from the use of vectors enabling tight control of TRAIL expression in
      vivo. To this aim, we constructed an adenoviral vector carrying the RU486
      dependent gene switch system for the regulable expression of recombinant TRAIL.
      Only was apoptotic recombinant TRAIL expressed and cytotoxicity observed upon
      binding of RU 486 to the inducible promoter. Expression levels and kinetics of
      recombinant TRAIL expression could be achieved by modulating the concentration of
      the inducer. As a broad implication, our data provide an alternative approach to
      circumvent the potential toxicity of TRAIL in future human trials and this system
      may be utilized to treat human cancer using a long-term expression vector.

PMID- 18059163
TI  - Development of novel chimeric transmembrane proteins for multimodality imaging of
      cancer cells.
AB  - Tracking the migration of cancer cells is essential to understanding the
      metastatic process. In order to facilitate the tracking of metastatic
      progression, we have generated transgenic cancer cell lines that express novel
      chimeric proteins composed of truncated human type II transmembrane proteins
      fused in-frame to a red fluorescence protein. These chimeric proteins have been
      engineered to display the fluorescence domain on the surface of cells. The three
      novel chimeric proteins exhibited high transient expression in several cancer
      cell lines. Membrane expression was well characterized in MCF-7 cell lines that
      stably express the chimeric proteins. Indirect immunocytochemistry of non
      premeablized cells demonstrated co-localization of endogenous red and green
      fluorescence labeled secondary antibody bound on the cell surfaces. Immunoblots
      of total protein prepared from membrane, cytosolic and nuclear fractions
      indicated that the chimeric proteins were mainly associated with the membrane
      fraction. Further evidence of the membrane expression of these proteins was
      confirmed by confocal microscopy. Moreover, the chimeric protein was detected on
      the cell surface by T2-weighted magnetic resonance imaging using anti-red
      fluorescence protein antibody and superparamagnetic iron oxide particles in vitro
      and by optical imaging in vivo. The development of this non-mammalian cell
      surface marker, that can be detected by multi-modality imaging, will find utility
      in non-invasive longitudinal tracking of biological processes including
      metastatic progression, solid tumor treatment regimes and the fate of cells used
      in cell therapies such as islet or stem cells.

PMID- 18059164
TI  - Expression of the local angiotensin II system in gastric cancer may facilitate
      lymphatic invasion and nodal spread.
AB  - PURPOSE: In this study we investigated the putative pathophysiological mechanism,
      by which angiotensin converting enzyme (ACE), and angiotensin II receptor (ATR)
      type 1 and 2 might contribute to cancer progression and lymph node metastasis in
      gastric cancer. MATERIALS AND METHODS: Local expression of ACE, AT1R and AT2R was
      investigated immunohistochemically in non-lesional tissue, primary tumors and
      lymph node metastases from 45 gastric cancer patients. The distribution of the
      ACE genotypes was studied in gastric cancer cell lines. In vitro cell
      proliferation, apoptosis and invasion assays were carried out in the presence of
      ACE, AT1R and AT2R inhibitors. RESULTS: ACE and AT2R were significantly
      upregulated in tumors and metastases, and expressed in the lymph node metastases
      of 26 (58%) and 40 (89%) gastric cancer patients, respectively. AT1R expression
      was higher in all tissues of metastatic cancers than in previous investigations.
      ACE, but not AT1R or AT2R, occasionally exhibited an increased expression in
      tumor cells directly surrounding lymph follicles. All three possible combinations
      of the ACE gene insertion/deletion polymorphism were found in gastric cancer cell
      lines, i.e., the DD- (AGS, MKN28), the II- (MKN45) and the ID-genotype (N87).
      ACE, AT1R and AT2R inhibition resulted in a significantly increased proliferation
      and a significant reduction in invasive ability of the N87 and MKN45 cell lines,
      with N87 exhibiting reduced apoptosis. CONCLUSIONS: Our study provides evidence
      of the expression of the local angiotensin II system in lymph node metastases,
      and that ACE-, AT1R- and AT2R-activity promotes tumor cell invasion.

PMID- 18059165
TI  - Generation of Her-2/neu vaccine utilizing idiotypic network cascade.
AB  - Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for
      the treatment of Her-2/neu-positive human cancer. Amplification and/or
      overexpression of Her-2/neu occur in multiple human malignancies and are
      associated with poor prognosis. The Her-2/neu proto-oncogene is a suitable target
      for cancer immunotherapy. Our strategy is active specific immunotherapy in which
      patients immunized with an anti- Id antibody mimicking Her-2/neu will generate
      sustained high titer Her-2/neu specific protective antibodies. We have used an
      anti-Her-2/neu murine monoclonal antibody 4D5 as the immunizing antibody (Ab1)
      against which monoclonal anti-Ids or Ab2s were generated in syngeneic mice. We
      have characterized one such anti-Id (Ab2) designated 6D12, which mimics a
      specific epitope of Her-2/neu as defined by Trastuzumab, and can be used as a
      surrogate antigen for Her-2/neu across the species barriers. Immunization of
      allogeneic mice or rabbits with 6D12 induced anti-anti-Id (Ab3), that
      specifically recognized Her-2/neu-positive tumor cells and lysed these cells in
      culture by antibody-dependent cellular cytotoxicity (ADCC). Monoclonal Ab3
      generated in mice against 6D12 inhibited the proliferation of Her-2/neu-positive
      SK-BR-3 cells in vitro in a dose dependent fashion and delayed the growth of Her
      2/neu transfected EL4-Her-2 cells in vivo. These data suggest the potential use
      of 6D12 as a vaccine for Her-2/neu-positive human cancer.

PMID- 18059166
TI  - AMPA antagonists inhibit the extracellular signal regulated kinase pathway and
      suppress lung cancer growth.
AB  - Antagonists at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type
      glutamate receptors limit growth of human cancers in vitro. However, the
      mechanism of anticancer action of AMPA antagonists is not known. Here we report
      that the AMPA antagonists GYKI 52466 and CFM-2 inhibit the extracellular signal
      regulated kinase (ERK1/2) pathway, an intracellular signaling cascade which is
      activated by growth factors and controls proliferation of lung adenocarcinoma
      cells. AMPA antagonists reduced phosphorylation of cAMP-responsive element
      binding protein (CREB), suppressed expression of cyclin D1, upregulated the cell
      cycle regulators and tumor suppressor proteins p21 and p53 and decreased number
      of lung adenocarcinoma cells in G2 and S phases of the cell cycle. These findings
      reveal potential mechanism of antiproliferative action of AMPA antagonists and
      indicate that this class of compounds may be useful in the therapy of human
      cancers.

PMID- 18059167
TI  - Inhibition of Stat3 activity by YC-1 enhances chemo-sensitivity in hepatocellular
      carcinoma.
AB  - The present study investigated the effect of YC-1, a novel anti-cancer agent, on
      the chemo-sensitivity of hepatocellular carcinoma (HCC). YC-1 was administered
      with chemo-cytotoxic drug, cisplatin, both in vitro and in vivo. YC-1 alone
      downregulated the expression of phosphorylated form of signal transducers and
      activators of transcription 3 (P-Stat3[705]), a key mediator in chemo-resistance.
      When combined with cisplatin, YC-1 further promoted tumor cell apoptosis,
      decreased the expression of P-Stat3(705), Bcl-xL, CyclinD1 and survivin, and
      induced the cleavage of caspase 9 and PARP. Overexpression of Stat3 reversed YC-1
      induced cell death. YC-1 inhibited Stat3 activity by enhancing the
      polyubiquitination of P-Stat3(705) induced by cisplatin. In the in vivo setting,
      YC-1 combined with cisplatin remarkably suppressed tumor growth in a HCC
      xenograft model, and this effect was also accompanied by YC-1 mediated
      downregulation of P-Stat3(705), Bcl-xL, Cyclin D1 and survivin, and induction of
      cleaved caspase 9 and PARP in the tumor tissues. In conclusion, the present study
      demonstrated a novel anti-cancer effect of YC-1 in enhancing chemo-sensitivity of
      HCC cells to cisplatin through a Stat3 dependent manner. This finding provides
      insight into design of a new therapeutic strategy to improve efficacy of
      chemotherapy in HCC patients.

PMID- 18059168
TI  - Study of immunotherapy of murine myeloma by an IL-21-based tumor vaccine in
      BALB/C mice.
AB  - The tumor cells can be recognized and eliminated by the power of the immune
      response has result in intense interest in the development of tumor vaccines
      transfected with plasmid DNA containing target genes, and the tumor vaccines are
      being evaluated as prophylactic and therapeutic vaccines for tumor. In current
      study, we designed a murine myeloma cell (SP2/0) vaccine containing mIL-21
      plasmid DNA and to evaluate its anti-tumor efficacy and analyze the mechanism of
      anti-tumor efficacy. It was upregulated obviously that the MHC-I molecule was
      expressed on SP2/0-mIL-21 tumor cells surface and the significant tumor
      regression and prolonged survival were observed in BALB/c mice injected with the
      SP2/0-mIL-21 tumor vaccine. The four mice without tumors growth were rechallenged
      with SP2/0 cells on the opposite site of the back and there was only one with
      growth a small tumor after 30 days and others remained tumor free. The cytotoxic
      activities of NK, CTLs and the IFN-gamma; were significantly increased
      respectively in immunized mice. The expression of I-TAC in the tumor tissue was
      upregulated and the tumor tissue were showed the tumor cells were apoptosis and a
      lots of infiltrating lymphocytes and phagocytes. We conclude that the autologous
      IL-21-producing tumor vaccine can induce strong cell-mediated immune response and
      it is a promising immune adjunctive modality to prevent or inhibit growth of
      SP2/0 cells in mice model.

PMID- 18059170
TI  - Macroautophagy-dependent, intralysosomal cleavage of a betaine homocysteine
      methyltransferase fusion protein requires stable multimerization.
AB  - Cargo-based assays have proven invaluable in the study of macroautophagy in yeast
      and mammalian cells. Proteomic analysis of autolysosomes identified the metabolic
      enzyme, betaine homocysteine methyltransferase (BHMT), as a potential cargo
      based, end-point marker for mammalian macroautophagy. To test whether degradation
      of BHMT can be used to measure macroautophagic flux in mammalian cells, we
      created a BHMT fusion protein (GST-BHMT) that demonstrates starvation-induced,
      site-specific fragmentation in a variety of cell lines. Subcellular fractionation
      studies show that the GST-BHMT fragment co-fractionates with vesicles containing
      lysosomal and autolysosomal markers. Furthermore, both pharmacological inhibitors
      of macroautophagy and depletion of macroautophagy-specific proteins reduce
      accumulation of the fragment. In the course of these studies, we observed that
      fragmentation of GST-BHMT did not occur in forms of the reporter with truncation
      or point mutations that destabilize oligomerization. Since stable oligomerization
      of BHMT is essential for its catalytic activity, a point mutation known to ablate
      BHMT activity was tested. We show that accumulation of the GST-BHMT fragment is
      not impaired in a catalytically inactive mutant, indicating that selective
      proteolysis of GST-BHMT requires stable quaternary structure independent of
      effects on activity. Also, the loss of fragmentation observed in the
      oligomerization deficient mutants does not seem to be due to a defect of
      sequestration and lysosomal loading, suggesting that disruption of stable
      quaternary structure affects the ability of a lysosomal protease to cleave the
      newly-delivered cargo. Finally, we propose that the cargo-based GST-BHMT assay
      will be a valuable addition to existing macroautophagy assays in mammalian cells.

PMID- 18059169
TI  - Hypoxia induces autophagic cell death in apoptosis-competent cells through a
      mechanism involving BNIP3.
AB  - Hypoxia (lack of oxygen) is a physiological stress often associated with solid
      tumors. Hypoxia correlates with poor prognosis since hypoxic regions within
      tumors are considered apoptosisresistant. Autophagy (cellular "self digestion")
      has been associated with hypoxia during cardiac ischemia and metabolic stress as
      a survival mechanism. However, although autophagy is best characterized as a
      survival response, it can also function as a mechanism of programmed cell death.
      Our results show that autophagic cell death is induced by hypoxia in cancer cells
      with intact apoptotic machinery. We have analyzed two glioma cell lines (U87,
      U373), two breast cancer cell lines (MDA-MB-231, ZR75) and one embryonic cell
      line (HEK293) for cell death response in hypoxia (<1% O(2)). Under normoxic
      conditions, all five cell lines undergo etoposide-induced apoptosis whereas
      hypoxia fails to induce these apoptotic responses. All five cell lines induce an
      autophagic response and undergo cell death in hypoxia. Hypoxia-induced cell death
      was reduced upon treatment with the autophagy inhibitor 3-methyladenine, but not
      with the caspase inhibitor z-VAD-fmk. By knocking down the autophagy proteins
      Beclin-1 or ATG5, hypoxia-induced cell death was also reduced. The pro-cell death
      Bcl-2 family member BNIP3 (Bcl-2/adenovirus E1B 19kDainteracting protein 3) is
      upregulated during hypoxia and is known to induce autophagy and cell death. We
      found that BNIP3 overexpression induced autophagy, while expression of BNIP3
      siRNA or a dominant-negative form of BNIP3 reduced hypoxia-induced autophagy.
      Taken together, these results suggest that prolonged hypoxia induces autophagic
      cell death in apoptosis-competent cells, through a mechanism involving BNIP3.

PMID- 18059172
TI  - Oral administration of attenuated S. typhimurium carrying shRNA-expressing
      vectors as a cancer therapeutic.
AB  - RNAi has been successfully applied in genomic research, and it also holds
      considerable promise as a therapeutic approach to suppress disease-causing gene
      expression. Here, we show that attenuated S. typhimurium were capable of
      delivering shRNA-expressing vectors to mammalian cells and inducing RNAi in vitro
      and in vivo. Upon oral administration, S. typhimurium carrying shRNA-expressing
      vectors targeting bcl2 induced significant gene silencing in murine melanoma
      cells that led to a remarkably delayed tumor growth and prolonged survival in the
      mouse model. These results suggest that bacteria mediated RNAi may be a new
      potent approach to the treatment of cancers.

PMID- 18059171
TI  - Viral evasion of autophagy.
AB  - Autophagy is an evolutionarily ancient pathway for survival during different
      forms of cellular stress, including infection with viruses and other
      intracellular pathogens. Autophagy may protect against viral infection through
      degradation of viral components (xenophagy), by promoting the survival or death
      of infected cells, through delivery of Toll-like receptor (TLR) ligands to
      endosomes to activate innate immunity, or by feeding antigens to MHC class II
      compartments to activate adaptive immunity. Given this integral role of autophagy
      in innate and adaptive antiviral immunity, selective pressure likely promoted the
      emergence of escape mechanisms by pathogenic viruses. This review will briefly
      summarize the current understanding of autophagy as an antiviral pathway, and
      then discuss strategies that viruses may utilize to evade this host defense
      mechanism.

PMID- 18059173
TI  - hADA2a and hADA3 are required for acetylation, transcriptional activity and
      proliferative effects of beta-catenin.
AB  - Beta-catenin is the key transcriptional activator of the Wnt pathway important
      for development and tissue homeostasis of multicellular organisms. Its
      deregulation contributes to many human cancers. The beta-catenin transcriptional
      activator complex continues to be defined, but already contains several proteins
      with chromatin remodeling activity. Here we show that two members of histone
      acetyltransferase complexes without enzymatic activity, hADA2a and hADA3, are
      required for full activity of beta-catenin. hADA2a and hADA3 physically interact
      with beta-catenin, and the interaction is mediated through Armadillo repeats 6
      through 12 and the C-terminal transactivation domain of beta-catenin. Both hADA2a
      and hADA3 reside with beta-catenin at the enhancer for the Wnt target gene c-Myc.
      RNA interference-mediated reduction of hADA2a and hADA3 results in reduced beta
      catenin acetylation, reduced activity in reporter gene assays and reduced
      activation of endogenous beta-catenin target genes. Overall, loss of hADA2a and
      hADA3 negatively impacts beta-catenin-mediated proliferation. Our studies
      identify hADA2a and hADA3 as crucial cofactors of beta-catenin that are likely
      involved in the assembly of transactivation-competent beta-catenin complexes at
      Wnt target genes.

PMID- 18059174
TI  - Biology of breast cancer bone metastasis.
AB  - Breast carcinoma ranks among the most prevalent malignancies in women. Breast
      carcinoma frequently metastasizes to bone and approximately 70% of patients with
      breast cancer have bone metastases, which generally are osteolytic lesions. They
      cause major morbidity and mortality in patients; and the available treatment
      options are limited. Bone-specific homing and colonization of cancer cells are
      important and interesting features of metastasis. There are complex and multiple
      steps in the process of bone metastasis; and the elaborate interaction between
      breast carcinoma and bone involves various cytokines, growth factors and cellular
      signals, which results in a vicious cycle and promotes tumor cell accumulation
      and osteolysis. Recent advances in molecular biology have resulted in major
      breakthroughs in our understanding of the pathogenesis of bone metastasis in
      breast cancer, which is critical in preventing metastasis, designing novel and
      targeted treatments and prolonging survival in this devastating condition.

PMID- 18059175
TI  - Development of Ad-mda7/IL-24-resistant lung cancer cell lines.
AB  - Many cancers can become resistant to repeated administration of even the most
      effective therapeutic agents. In developing adenoviral mda-7/IL-24 (Ad-mda-7/IL
      24) therapy for lung cancer, we have anticipated this potential clinical problem
      by attempting to identify the molecular mechanisms of Ad-mda7/IL-24 resistance in
      several Ad-mda7/IL-24-resistant lung cancer cell lines that we have developed.
      For the present study, we established four Admda7- resistant cell lines by
      repeated selection of resistant clones of parental Ad-mda7-sensitive A549 cells:
      two lines (A549R1 and A549R2) resistant to both adenoviral vector and the mda-7
      gene and two (A549R3 and A549R4) resistant to the therapeutic mda-7 gene only. As
      shown by western blot analysis of several known anti-apoptotic proteins, parental
      A549 and resistant A549R3 cells expressed similar levels of AKT and
      phosphorylated AKT (p-AKT), whereas resistant A549R3 and A549R4 cells expressed
      higher levels of bcl-2 and lower levels of bcl-xL than did their parental cells.
      As shown by flow-cytometric analysis, treating resistant A549R3 and A549R4 cells
      with a combination of Ad-mda7 and 17-allyl-amino-17-demethoxygeldanamycin (17AAG)
      (50 nM) for 48 hours enhanced apoptosis. Together, these in vitro findings
      indicate that an antiapoptotic mechanism may underlie Ad-mda7 resistance and that
      such resistance can be overcome by addition of 17AAG. Further investigations
      along these lines are warranted.

PMID- 18059176
TI  - Ciprofloxacin-induced G2 arrest and apoptosis in TK6 lymphoblastoid cells is not
      dependent on DNA double-strand break formation.
AB  - Drugs developed for the treatment of conditions other than neoplasia can also
      show promise as potential antitumor agents. The fluoroquinolone antibiotic
      ciprofloxacin (CPFX) is known to modulate cycle cell progression and apoptosis in
      cancer cells, and is thought to induce DNA double-strand breaks (DSBs) via
      topoisomerase II (topo II) inhibition and stabilized cleavage complex (SCC)
      formation. DSBs trigger Ser-139 phosphorylation of histone H2AX (gammaH2AX) by PI
      3-like kinases including ATM; gammaH2AX can serve as a marker of DNA damage when
      measured in situ using immunocytochemistry and flow cytometry. The aim of the
      present study was to investigate the relationship between CPFX-mediated DNA
      damage and induction of apoptosis in human lymphoblastoid cells and
      phytohaemagglutinin (PHA)-stimulated lymphocytes (Lymphs). Treatment of TK6 cells
      (wild-type p53) with 100 microg/ml CPFX for 2-10 h produced no increase in
      gammaH2AX; to the contrary, its level in S phase cells was reduced at 10 h
      compared to controls. Nevertheless, stabilization of topo IIalpha, ATM Ser-1981
      phosphorylation and G(2) arrest was observed in TK6 cells exposed to CPFX for >
      or = 4 h. However, following 24 h treatment, gammaH2AX was dramatically increased
      in a sub-population of cells indicating the onset of apoptosis (confirmed by
      presence of activated caspase 3). CPFX had a similar lack of effect on induction
      of gammaH2AX at early time points in WTK1 and NH32 cells (devoid of functional
      p53) and proliferating Lymphs, however, induction of apoptosis was less
      pronounced than in TK6 cells. Formation of SCC and activation of ATM (but lack of
      gammaH2AX induction) indicates topo II-mediated chromatin or DNA changes in the
      absence of DSBs; ATM activation apparently triggers the G(2)M checkpoint leading
      to G(2) arrest. The subsequent induction of apoptosis appears to be facilitated
      by functional p53. CPFX may therefore have a potential use as a chemotherapeutic
      agent in the treatment of lymphoblast-derived cancer.

PMID- 18059177
TI  - The effect of fatty acid-CoA ligase 4 on the growth of hepatic cancer cells.
AB  - In this study, we detected the expression of FACL4 mRNA in 40 patients with
      hepatic carcinoma and its adjacent normal tissues by semi-quantitative RT-PCR.
      The changes of proliferation and apoptosis of hepatic cancer cell line HepG2 with
      FACL4 protein expression were examined by MTT and flow cytometry respectively
      after FACL4 selective inhibitor triacsin C treatment. The activity related to
      apoptosis of proteinases, caspase-3, caspase-8 and caspase-9, were detected by
      colorimetry. The expression related to apoptosis of protein, wt-p53, Bax and Bcl
      2, in HepG2 cells were evaluated by S-P immunocytochemical dyeing. The results
      were: (1) FACL4 mRNA was expressed in 95.0% of hepatic cancer tissue, while the
      positive expression of FACL4 mRNA was 82.5% in cancer adjacent normal liver
      tissues. Moreover, there was a statistically significant increased in quantity of
      FACL4 mRNA in cancer tissues compared with adjacent normal liver tissues. (2) The
      concentration of triacsin C (0.5-2 mg/L) could inhibit the proliferation and
      induce the apoptosis of HepG2 cells significantly in a dose- and time-effect. (3)
      During the apoptosis of HepG2 cells induced by triacsin C, flow cytometry coupled
      with Rhodamine 123 dyeing showed that mitochondrial transmembrane potential of
      HepG2 declined significantly, and the activity of caspase-9 and caspase-3
      increased more remarkably than caspase-8. Besides, the increased apoptosis was
      accompanied by increased Bax, and decreased wtp53 and Bcl-2 protein levels. The
      present study suggested that FACL4 might play a role in the growth of hepatic
      cancer cells. FACL4 selective inhibitor triacsin C leads to a marked growth
      inhibition of human liver tumor cells, based on the inhibition of proliferation
      and induction of apoptosis. The apoptotic process was mediated by intrinsic
      mitochondrial apoptotic pathway due to activation of caspase-9 and caspase-3. The
      increased apoptosis was accompanied by upregulation of Bax, and decreased wt-p53
      and Bcl-2 protein level.

PMID- 18059178
TI  - Circulating biomarkers of bevacizumab activity in patients with breast cancer.
AB  - PURPOSE: Noninvasive markers of anti-vascular endothelial growth factor (VEGF)
      therapy are needed. Soluble vascular cell adhesion molecule (sVCAM-1), soluble
      VEGF receptor-2 (sVEGFR-2), and plasma VEGF levels were assessed as potential
      biomarkers of therapy with bevacizumab. Tumor samples were evaluated for VEGFR-2
      mutations before and after bevacizumab. EXPERIMENTAL DESIGN: Twenty-one patients
      with breast cancer underwent neoadjuvant treatment with bevacizumab for 1 cycle
      followed by 6 cycles of bevacizumab, chemotherapy, and filgrastim. Peripheral
      blood samples were collected at baseline, post cycles 1, 4 and 7. sVCAM-1, VEGF
      and sVEGFR-2 levels were measured by enzyme-linked immunosorbent assay (ELISA).
      Exons 17-26 of VEGFR-2 were sequenced on tissue samples from 20 patients at
      baseline and post cycle 1 to evaluate for tumor mutations. RESULTS: From baseline
      to post cycle 1, sVCAM-1 and sVEGFR-2 values increased by a median of 180.5 ng/ml
      (p < 0.0001) and 1927 ng/ml respectively (p = 0.0003). Baseline VEGF, sVEGFR-2,
      and sVCAM-1 levels nor changes in sVEGFR-2 and sVCAM-1 levels were associated
      with clinical response. Median baseline sVEGFR-2 levels were 11322 ng/ml and 7524
      ng/ml in patients with (n = 5) and without (n = 6) wound healing problems
      respectively, (p = 0.052). In 40 samples where tumor VEGFR-2 sequencing was
      obtained, no mutations were seen compared to the reference sequence. CONCLUSIONS:
      sVCAM-1 and sVEGFR-2 values increased significantly after treatment with
      bevacizumab, possibly due to compensatory mechanisms secondary to VEGF
      inhibition. sVEGFR-2 levels were somewhat higher in patients with wound healing
      problems and may potentially predict patients at higher risk of this
      complication. There were no tumor VEGFR-2 mutations.

PMID- 18059179
TI  - Allele-specific expression in the germline of patients with familial pancreatic
      cancer: an unbiased approach to cancer gene discovery.
AB  - Physiologic allele-specific expression (ASE) in germline tissues occurs during
      random X-chromosome inactivation and in genomic imprinting, wherein the two
      alleles of a gene in a heterozygous individual are not expressed equally. Recent
      studies have confirmed the existence of ASE in apparently non-imprinted autosomal
      genes; however, the extent of ASE in the human genome is unknown. We explored ASE
      in lymphoblastoid cell lines of 145 individuals using an oligonucleotide array
      based assay. ASE of autosomal genes was found to be a very common phenomenon in
      approximately 20% of heterozygotes at 78% of SNPs at 84% of the genes examined.
      Comparison of 100 affected individuals from familial pancreatic cancer kindreds
      and 45 controls revealed three types of changes in the germline: (a) loss of ASE,
      (b) gain of ASE, and, (c) rare instances of "extreme" (near monoallelic) ASE. The
      latter changes identified heterozygous deleterious mutations in a subset of these
      genes. Consequently, an ASE assay efficiently identifies candidate disease genes
      with altered germline expression properties as compared to controls, and provides
      insights into mechanisms that confer an inherited disease risk for pancreatic
      cancer.

PMID- 18059180
TI  - Molecular basis of pathogenesis, prognosis and therapy in chronic lymphocytic
      leukaemia.
AB  - B-cell chronic lymphocytic leukemia (CLL) is caused by the abnormal accumulation
      of non-functional B-cells in peripheral blood and bone marrow. However, the
      precise aetiology and mechanism of the disease are unclear. Recently, progress
      has been made in the identification of both the genetic deficiencies and
      environmental factors that may underlie CLL. This has provided some clues to the
      nature of the disease, but no definitive cures. Although treatment has increased
      remission time, at present the disease is not curable by conventional therapy.
      Further studies of the pathogenesis of CLL are needed, as are the development of
      suitable cell lines and animal models in which to study it. This review
      summarises the most recent progress in CLL with emphasis on molecular events and
      possible implications in therapy.

PMID- 18059181
TI  - Modulation of death receptors by cancer therapeutic agents.
AB  - Death receptors are important modulators of the extrinsic apoptotic pathway.
      Activating certain death receptors such as death receptors for tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) (i.e., DR4 and DR5) selectively
      kills cancer cells via induction of apoptosis while sparing normal cells. Thus,
      soluble recombinant TRAIL and agonistic antibodies to DR4 or DR5 have progressed
      to phase I and phase II clinical trials. Many cancer therapeutic drugs including
      chemotherapeutic agents have been shown to induce the expression or
      redistribution at the cell surface of death receptors including TRAIL death
      receptors. In addition, chemotherapeutic agents have also been shown to enhance
      induction of apoptosis by TRAIL or agonistic antibodies or overcome cell
      resistance to TRAIL or agonistic antibodies. Targeted induction of apoptosis by
      activation of the death receptor-mediated extrinsic apoptotic pathway should be
      an ideal therapeutic strategy to eliminate cancer cells. Therefore, death
      receptors, particularly TRAIL death receptors, have emerged as an important
      cancer therapeutic target. This article will focus on reviewing and discussing
      the modulation of death receptors by cancer therapeutic agents and its
      implications in cancer therapy.

PMID- 18059182
TI  - Protein phosphatase 1H, overexpressed in colon adenocarcinoma, is associated with
      CSE1L.
AB  - In search for a new anticancer drug target, we explored genes involved in colon
      adenocarcinoma development through dysregulation of a signal transduction
      pathway. By using the gene expression profile database, we found protein
      phosphatase 1H (PPM1H), belonging to the protein phosphatase 2C (PP2C) family,
      upregulated in colon adenocarcinomas compared with normal colon tissues. RT-PCR
      analysis verified the elevated level of PPM1H expression in colon cancer cell
      lines relative to a normal colon cell line. PPM1H encodes a protein with a
      molecular mass of approximately 50 kDa that resides in the cytoplasm. PPM1H fused
      with maltose-binding protein expressed in E. coli exhibited phosphatase activity
      characteristic of the PP2C family. Co-immunoprecipitation coupled with mass
      spectrometry analysis identified CSE1L, a proliferation and apoptosis-related
      protein, as a PPM1H-interacting protein. Native, but not inactive, PPM1H
      expressed in HeLa cells increased the mobility of CSE1L on SDS gels and a similar
      mobility shift was observed for purified CSE1L after treatment with PPM1H in
      vitro, supporting the notion that CSE1L is a substrate of PPM1H. Dominant
      negative PPM1H protected HeLa cells from cell death triggered by staurosporine or
      taxol. Additionally, knockdown of PPM1H expression with small interfering RNAs
      suppressed the growth of MCF-7 cells weakly but consistently. PPM1H controls cell
      cycle and proliferation of cancer cells potentially through dephosphorylation of
      CSE1L and might be a new target of anticancer drugs.

PMID- 18059183
TI  - hTERT-targeted RNA interference inhibits tumorigenicity and motility of HCT116
      cells.
AB  - Telomerase is proposed as an anticancer target. Increasing evidence suggests that
      telomerase is involved in functions independent of telomere-extension activity.
      In this study, we designed a small interfering RNA (siRNA) targeting human
      telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase.
      Using transient and persistent transfection of hTERT siRNA into telomerase
      positive human colon carcinoma HCT116 cells, we demonstrated that hTERT siRNA
      suppresses hTERT expression and leads to inhibition of telomerase activity and
      HCT116 cell growth and in vivo tumorigenicity in nude mice. Further analysis
      indicated that depletion of hTERT reduces cell adhesion, migration, and invasion
      prior to inhibition of cell proliferation. Downregulation of hTERT also decreased
      the expression levels of adhesion- and motility-related proteins, in particular c
      Met and integrins. The lack of detectable changes in telomere length showed that
      downregulation of hTERT in the present system had no significant effect on
      telomere-extension activity. Taken together, our results highlight the
      therapeutic potential of a novel hTERT siRNA and suggest that hTERT is involved
      in the regulation of cell motility in a telomere-independent manner.

PMID- 18059184
TI  - Cytokine polymorphisms and gastric cancer risk: an evolving view.
AB  - More than 20 years after the identification of Helicobacter pylori as a human
      pathogen, gastric cancer continues to be a leading cause of cancer deaths
      worldwide. Genetic association studies have the potential for helping to identify
      those at greatest risk for developing gastric cancer subsequent to infection by
      H. pylori. IL1B promoter polymorphisms have been supported by several meta
      analyses as being associated with gastric cancer risk. In this review, we discuss
      challenges in experimental design of gene association studies in gastric cancer,
      with attention to gene-environment interactions that may lead to inconsistency in
      findings across populations.

PMID- 18059185
TI  - Response and determinants of cancer cell susceptibility to PI3K inhibitors:
      combined targeting of PI3K and Mek1 as an effective anticancer strategy.
AB  - While small molecule inhibitors of the phosphatidylinositide-3-kinase (PI3K) are
      expected to impact the development of new cancer therapy, the tumor types and
      underlying cellular pathways determining inhibitor response remain poorly
      defined. In this report, we have studied anti-proliferative effects of the PI3K
      inhibitors WAY-266176 and WAY-266175 in a panel of histologically diverse cancer
      cells. Inactivation of PI3K caused potent growth suppression in some cells
      (MDA468, BT549, MDA361, MCF7, LNCap, PC3MM2) but minimal suppression in others
      (MDA231, MDA435, DU145, HCT116, A549), which correlated with a differential down
      regulation of cyclin D1, c-Myc, and induction of apoptosis. A heightened
      PI3K/AKT/mTOR signaling was linked to the sensitive phenotype but did not
      generally predict inhibitor response. Interestingly, the resistant cells all
      displayed an elevated phospho-ERK that remained elevated after serum deprivation.
      In HCT116 cells, activation mutations in the PI3K catalytic subunit PIK3CA and Ki
      Ras correlated with a resistant phenotype, which was partially sensitized by
      homologous replacement with the wild-type Ki-Ras but not by deletion of cellular
      PTEN. Depletion of Mek1 via siRNA in resistant cells enhanced PI3K inhibitor
      induced growth suppression. Moreover, a profoundly augmented growth suppression
      and apoptosis were achieved in resistant cells by combination treatment with WAY
      266176/WAY-266175 and Mek1 kinase inhibitor CI-1040 or UO126. The combination
      therapy efficiently inhibited mitogenic signaling and reduced expression of
      cyclin D1 and c-Myc. Our results identify deregulation of the Ras/Raf/Mek/ERK
      pathway as a dominant determinant in cancer cell resistance to PI3K inhibitors
      and highlight combined targeting of PI3K and Mek1 as an effective anticancer
      strategy.

PMID- 18059186
TI  - Silencing of Wnt-1 by siRNA induces apoptosis of MCF-7 human breast cancer cells.
AB  - OBJECTIVE: Wnt family of secreted-type glycoproteins plays key role in
      carcinogenesis and embryogenesis. Signals of Wnts are transduced through seven
      transmembrane-type Wnt receptors encoded by Frizzled (Fzd) genes to the beta
      catenin-Tcf pathway, the c-Jun-N-terminal kinase (JNK) pathway or the Ca(2+)
      releasing pathway. Aberrant activation of the Wnt/beta-catenin signaling pathway
      is associated with a variety of human cancers. In human breast cancer, evidence
      of beta-catenin accumulation implies that the canonical Wnt signaling pathway is
      active in over 50% of carcinomas. RESULTS: We found that in breast cancer cells
      overexpressing Wnt-1 siRNA anti-Wnt-1 induced apoptosis and caused changes in
      downstream proteins levels. Among treated cells there were 71% apoptotic cells in
      comparison to cells treated with scrambled siRNA (6%) and control cells (6%)
      after 48 h (p < 0.01). METHODS: To examine if Wnt-1 signal is essential for
      cancer cell survival, we investigated the effect of Wnt-1 gene silencing in
      triggering of apoptosis in MCF-7 breast cancer cell line. Light microscopy,
      viability/cytotoxicity tests, flow cytometry, real-time PCR and western blotting
      were used for evaluation of the morphological features of cell death, percentage
      of apoptotic cells, Wnt-1 mRNA and protein level. CONCLUSION: Our results
      significantly indicate that anti-Wnt-1 siRNA inhibits Wnt-1 signaling, inducing
      apoptosis in human breast cancer MCF-7 cells and thus may serve as a potential
      anti-cancer drug.

PMID- 18059188
TI  - Chimeric toxins inhibit growth of primary oral squamous cell carcinoma cells.
AB  - Treatment of oral squamous cell carcinoma (OSCC) is currently based on surgery
      and radiotherapy. Prolongation of the survival time of patients with progressing
      tumors is infrequently achieved. To improve the therapeutic options, targeted
      therapies are a favorable alternative. Therefore, we analyzed the effect of a
      chimeric toxin (CT) named SE consisting of the epidermal growth factor and the
      plant protein toxin saporin from Saponaria officinalis. A second construct (SA2E)
      additionally contains a peptidic adapter designed to enhance efficacy of the CT
      in vivo and to reduce side effects. The IC(50) values for an OSCC cell line (BHY)
      were 0.27 nM and 0.73 nM for SE and SA2E, respectively, while fibroblasts
      remained unaffected. To investigate primary tumor cells, we developed a technique
      to analyze freshly prepared OSCC cells of 28 patients in a stem cell assay
      directly after surgery. Cells were treated for 1 h with the CTs, subsequently
      seeded into soft agar and colony growth determined after 1-2 weeks In spite of
      the short time of CT incubation, the amount of colonies was reduced to about 78%
      by 10 nM and to 69% by 100 nM of either toxin. A combined application of 10 nM
      SA2E with a saponin from Gypsophila paniculata reduced the amount of surviving
      cells to 68%. The results demonstrate the impact of the CTs on OSCC cells and
      depict that the stem cell assay is suitable to determine the potential of anti
      tumor drugs before studies in vivo will be initiated.

PMID- 18059187
TI  - Application of doxorubicin-induced rAAV2-p53 gene delivery in combined
      chemotherapy and gene therapy for hepatocellular carcinoma.
AB  - p53 gene transfer has been proposed as a potential therapeutic option for
      treatment of hepatocellular carcinoma (HCC). Compared to other commonly used gene
      transfer vectors such as adenovirus and retrovirus, recombinant adeno-associated
      virus serotype 2 (rAAV2) has shown promising results in human clinical trials.
      Significant enhancement in the gene transfer efficiency is needed, however, for
      HCC applications. In the present study, we applied chemotherapy drug Doxorubicin
      (DOX) to induce rAAV2 transduction of hepatomas. Using reporter assays, we showed
      that the DOX-treated hepatomas became more susceptible to rAAV2 infection in
      comparison to untreated controls: the permissiveness increased >350-fold and >120
      fold for HepG2 (p53 wild-type) and Hep3B (p53 null) hepatomas, respectively.
      Using the induced permissiveness, we applied rAAV2-p53 transduction to restore
      p53 expression in the p53-null Hep3B hepatomas. Compared to rAAV2-p53
      transduction alone, rAAV2-p53 transduction with DOX resulted in a >16-fold
      induction of p53 expression. The transduced Hep3B expressed as much as 380% more
      immunoreactive p53 in comparison to the wild-type p53 expression in the HepG2
      hepatomas. Significantly, when Hep3B cells were treated with 0.5 muM of DOX and
      rAAV2-p53 (MOI = 10) for twelve hours, the cell viability dropped to 66% four
      days after the administration. This decrease in cell viability was similar to
      that of treatment with 1 microM of DOX alone in the absence of rAAV2. The 50%
      reduction in DOX administration--from 1 microM to 0.5 microM--revealed the
      antitumor property of the rAAV2-p53 transduction as well as the joint
      cytotoxicity of DOX and rAAV2-p53 against the p53-null hepatomas. We conclude
      that DOX mediates the enhancement effect on rAAV2 transduction of human
      hepatomas. Combined DOX and rAAV2-p53 administration may facilitate more
      efficient treatment for the HCC caused by p53 mutations.

PMID- 18059189
TI  - Cl-IB-MECA inhibits human thyroid cancer cell proliferation independently of A3
      adenosine receptor activation.
AB  - A3 adenosine receptor (A3AR) agonists have been reported to modulate cellular
      proliferation. This work was aimed to investigate the expression and the possible
      implication of A3AR in the human thyroid carcinomas. Normal thyroid tissue
      samples did not express A3 adenosine receptor, while primary thyroid cancer
      tissues expressed high level of A3AR, as determined by immunohistochemistry
      analysis. In human papillary thyroid carcinoma cell line, NPA, at concentrations
      > or =10 microM, the A3AR-selective agonist 2-chloro-N(6)-(3-iodobenzyl)adenosine
      5'-N-methylcarboxamide (Cl-IB-MECA) produced inhibition of cell growth, by
      blocking the G(1) cell cycle phase in a concentration- and time-dependent manner.
      This effect was well correlated with a reduction of protein expression of cyclins
      D1 and E2 after 24 hours of Cl-IB-MECA treatment. Moreover Cl-IB-MECA induced
      dephosphorylation of ERK1/2 in a time- and concentration-dependent manner, which
      in turn inhibits cell proliferation. The effect of Cl-IB-MECA was not prevented
      by A3AR antagonists, MRS1191 or MRS1523 or FA385. Furthermore, neither nucleoside
      transporter inhibitors, Dypiridamole and NBTI, nor the A1, A2A and A2B receptors
      antagonists were able to block the response to Cl-IB-MECA. Although Cl-IB-MECA
      has been shown to influence cell death and survival in other systems through an
      A3AR-mediated mechanism, in NPA cells the growth inhibition induced by micromolar
      concentrations of Cl-IB-MECA is not related to A3AR activation and hence that its
      effects on human papillary carcinoma cell line seem to be independent of the
      presence of this receptor subtype.

PMID- 18059190
TI  - Lyprinol only partially improves indicators of small intestinal integrity in a
      rat model of 5-fluorouracil-induced mucositis.
AB  - BACKGROUND: Intestinal mucositis is a common and debilitating side-effect of
      chemotherapy, associated with severe small intestinal inflammation. Marine oils,
      such as Lyprinol, a lipid extract derived from New Zealand Green-lipped Mussels,
      rich in long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA), have
      demonstrated therapeutic potential for the treatment of inflammatory conditions.
      We assessed the effects of Lyprinol on the severity of 5-fluorouracil (5-FU)
      induced mucositis in female Dark Agouti rats. RESULTS: Small intestinal weight
      was significantly greater in rats treated with 5-FU+HDL, 5-FU+LDL and 5-FU+FO
      compared to 5-FU-treated controls (p < 0.05). Myeloperoxidase activity in the
      proximal and mid small intestine were significantly lower in 5-FU+OO-treated rats
      compared to 5-FU+vehicle-treated controls (p < 0.05). Histological damage
      severity was elevated in 5-FU+vehicle, 5-FU+OO and 5-FU+FO-treated rats compared
      to saline-treated controls, but not in rats treated with 5-FU+HDL or 5-FU+LDL.
      SBT results and biochemically-assessed sucrase activity were lower in all 5-FU
      treated rats compared to saline-treated controls. 5-FU+HDL treated animals had
      significantly longer crypts and increased proliferation in the mid small
      intestine compared to 5-FU+vehicle rats (p < 0.05). CONCLUSION: Lyprinol
      treatment in rats with 5-FU-induced mucositis only minimally decreased indicators
      of intestinal integrity. Further studies of marine oils high in omega-3 PUFA
      content are warranted for the potential prophylactic treatment of intestinal
      mucositis. METHODS: Rats were allocated to six groups (n = 8/group);
      Saline+vehicle, 5-FU+vehicle, 5-FU+high-dose Lyprinol (5-FU+HDL), 5-FU+low-dose
      Lyprinol (5-FU+LDL), 5-FU+olive oil (5-FU+OO), and 5-FU+fish oil (5-FU+FO).
      Treatments were administered via oro-gastric gavage from days 0-7. Mucositis was
      induced on day 5 by 5-FU injection (150mg/kg i.p.). (13)C-sucrose breath tests
      (SBT) were conducted on days 0, 5 and 8 to assess small intestinal function. Rats
      were sacrificed on day 8 and small intestinal tissues collected for histological
      and biochemical analysis.

PMID- 18059191
TI  - miR-210 links hypoxia with cell cycle regulation and is deleted in human
      epithelial ovarian cancer.
AB  - Tumor growth results in hypoxia. Understanding the mechanisms of gene expression
      reprogramming under hypoxia may provide important clues to cancer pathogenesis.
      We studied miRNA genes that are regulated by hypoxia in ovarian cancer cell lines
      by TaqMan miRNA assay containing 157 mature miRNAs. MiR-210 was the most
      prominent miRNA consistently stimulated under hypoxic conditions. We provide
      evidence for the involvement of the HIF signaling pathway in miR-210 regulation.
      Biocomputational analysis and in vitro assays demonstrated that e2f transcription
      factor 3 (e2f3), a key protein in cell cycle, is regulated by miR-210. E2F3 was
      further confirmed to be downregulated at the protein level upon induction of miR
      210. Importantly, we found remarkably high frequency of miR-210 gene copy
      deletions in ovarian cancer patients (64%, n = 114) and that gene copy number
      correlates with miR-210 expression levels. Taken together, our results indicate
      that miR-210 plays a crucial role in tumor onset as a key regulator of the
      hypoxia response and provide evidence for a link between hypoxia and the
      regulation of cell cycle.

PMID- 18059192
TI  - The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro
      and in vivo.
AB  - Mesenchymal stem cells (MSCs) play an important role in the development and
      growth of tumor cells. The purpose of this study is to confirm the effect of MSCs
      on tumor cell growth in vitro and in vivo and to elucidate the mechanism. MSCs
      were isolated from mouse bone marrow and cocultured with murine hepatoma H22,
      lymphoma (YAC-1 and EL-4) and rat insulinoma INS-1 cell lines. The growth
      inhibitory effect of MSCs on tumor cells was tested through MTT and 3H-TdR
      incorporation assay. The apoptosis induction effect of MSCs on tumor cells was
      assessed with flow cytometry (FCM) and RT-PCR assay. MSCs were inoculated into
      BALB/c mice alone or coinoculated with ascitogenous hepatoma cells
      intraperitonealy, respectively. The tumor growth inhibition of MSCs was
      investigaed through the incidence and volume of ascites formation, and the
      immunosuppression effect was studied with splenocyte response to ConA stimulation
      test and T cell subsets analysis (FCM). The results showed that MSCs exhibited a
      number-dependent growth inhibitory effect on murine tumor cell lines in vitro and
      inhibited the growth of ascitogenous hepatoma cells in vivo without host
      immunosuppression. MSCs could upregulate tumor cells mRNA expression of cell
      cycle negative regulator p21 and apoptosis associated protease caspase 3. The
      findings of this experimental study demonstrated that MSCs had potential
      inhibitory effects on tumor cell growth in vitro and in vivo without host
      immunosuppression, by inducing apoptotic cell death and G(0)/G(1) phase arrest of
      cancer cells.

PMID- 18059194
TI  - Sensory and regulatory RNAs in prokaryotes: a new German research focus.

PMID- 18059193
TI  - Mechanisms of Cables 1 gene inactivation in human ovarian cancer development.
AB  - Cables 1, a cyclin-dependent kinase binding protein, is primarily involved in
      cell cycle regulation. Loss of nuclear Cables 1 expression is observed in human
      colon, lung and endometrial cancers. We previously reported that loss of nuclear
      Cables 1 expression was also observed with high frequency in a limited sample set
      of human ovarian carcinomas, although the mechanisms underlying loss of nuclear
      Cables 1 expression remained unknown. Our present objective was to examine Cables
      1 expression in ovarian cancer in greater detail, and determine the predominant
      mechanisms of Cables 1 loss. We assessed potential genetic and epigenetic
      modifications of the Cables 1 locus through analyses of mutation, polymorphisms,
      loss of heterozygosity and DNA methylation. We observed a marked loss of nuclear
      Cables 1 expression in serous and endometrioid ovarian carcinomas that correlated
      with decreased Cables 1 mRNA levels. Although we detected no Cables 1 mutations,
      there was evidence of LOH at the Cables 1 locus and epigenetic modification of
      the Cables 1 promoter region in a subset of ovarian carcinomas and established
      cancer cell lines. From a functional perspective, over-expression of Cables 1
      induced apoptosis, whereas, knockdown of Cables 1 negated this effect. Together
      these findings suggest that multiple mechanisms underlie the loss of Cables 1
      expression in ovarian cancer cells, supporting the hypothesis that Cables 1 is a
      tumor suppressor in human ovarian cancer.

PMID- 18059195
TI  - Nurses' knowledge of heart failure self-management.
AB  - Heart failure (HF) is increasing in prevalence. Patient education is essential
      and is included in both ambulatory and hospital performance measures used to
      ensure quality care. Nurses are often the primary providers of education to
      patients with HF. This study assessed nurses' knowledge of basic principles of HF
      self-management. The study surveyed 49 nurses who regularly provided care to
      patients with HF at a hospital in the southeastern United States. A 20-item,
      true/false survey was administered to participants. Mean HF self-management
      knowledge score was 15.97 (79.85% correct). Consistent with previous studies,
      nurses scored lowest on knowledge related to transient dizziness (16.3% answered
      correctly), daily weight monitoring (36.2% answered correctly), and asymptomatic
      hypotension (58.3% answered correctly). Findings confirm previous work suggesting
      that nurses may not be adequately prepared to educate patients with HF about self
      management.

PMID- 18059196
TI  - Impact of the implementation of telemanagement on a disease management program in
      an elderly heart failure cohort.
AB  - The purpose of the present investigation is to examine the impact of a
      telemanagement component on an outpatient disease management program in patients
      with heart failure (HF). A total of 282 patients in whom HF was diagnosed and who
      were enrolled in an outpatient HF program were included in this analysis. One
      hundred fifty-eight patients additionally participated in a self-directed
      telemanagement component. The remaining 124 patients received care at an HF
      clinic but declined telemanagement. During the 7-month tracking period, 19
      patients in the HF clinic plus telemanagement group and 53 patients in the HF
      clinic only group were hospitalized for cardiac reasons (log rank, 36.0; P<.001).
      The HF clinic only group had a significantly higher risk for hospitalization
      (hazard ratio, 4.0; 95% confidence interval, 2.4-6.7; P<.001). The results of the
      present study indicate that telemanagement is an important component of a disease
      management program in patients with HF.

PMID- 18059197
TI  - Readiness to exercise: a comparison of 3 instruments and an interview.
AB  - Exercise stage of change (ESOC), or readiness to exercise, has been measured
      using at least 13 instruments and 4 interviews, yet no comparison studies are
      available to determine optimal measures for use by health care providers. This
      pilot study compares ESOC classification between 3 instruments (scale-ladder,
      scale-true/false, and scale-5 choice); explores the feasibility of using a face
      to-face structured interview; compares classification between instruments and
      interview; and examines the influence of sex, age, and education level on stage
      classification. Thirty healthy adults completed ESOC instruments in random order
      and then the interview. Scale-ladder and scale-true/false instruments exhibited
      almost perfect agreement (weighted kappa, 0.897). All instruments exhibited
      substantial agreement with interview (weighted kappa, 0.620-0.790). Stage
      classification did not differ significantly by sex, age, or education level. The
      authors recommend word clarification revision of the scale-5 choice instrument
      and further testing of the interview.

PMID- 18059198
TI  - Can intensive statin therapy halt the progression of atherosclerosis? Recent
      evidence and potential implications for patient management.
AB  - A number of studies using various imaging techniques have demonstrated that
      intensive lipid lowering with statins can halt or delay the progression of
      atherosclerosis and even, in some cases, lead to plaque regression. Improvements
      in atheroma burden with intensive statin therapy appear to be related not just to
      decreasing low-density lipoprotein cholesterol but also to anti-inflammatory and
      antiproliferative effects. Clinical trial results also suggest that achieving low
      density lipoprotein cholesterol levels even lower than those currently
      recommended can produce improved clinical outcomes across a range of patient
      types. Given this body of evidence, it appears appropriate to use intensive
      statin therapy to treat dyslipidemic patients at high risk for coronary heart
      disease.

PMID- 18059199
TI  - Current understanding of peripartum cardiomyopathy.

PMID- 18059200
TI  - The European Council on Cardiovascular Nursing and Allied Professions: toward
      promoting excellence in cardiovascular care.

PMID- 18059201
TI  - Dronedarone: in quest of the ideal antiarrhythmic drug.

PMID- 18059202
TI  - Why do some patients have a delta wave?

PMID- 18059203
TI  - New trends in insulin resistance: the role of mineralocorticoids.

PMID- 18059204
TI  - The cardiometabolic syndrome and cardiovascular disease in racial and ethnic
      minorities: new areas of research and intervention.

PMID- 18059205
TI  - Avoiding the looming Latino/Hispanic cardiovascular health crisis: a call to
      action.
AB  - Cardiovascular disease (CVD) is the leading cause of death among the largest and
      fastest growing ethnic minority in the United States, Latinos/Hispanics. To
      review recent findings on the prevalence of CVD, CVD risk factors, and related
      illnesses in the US Latino/Hispanic population, an extensive PubMed and Internet
      literature search for studies published from January 1995 to July 2005 was
      conducted, using a combination of search terms. Data validity was assessed based
      on the quality of the source and a consensus of the authors on perceived
      validity. The review found limitations in current research as well as treatment
      methods and options for Latino/Hispanic persons at risk for developing CVD and
      related illnesses. Because of these limitations and the large public health
      concern, additional research is required to fully determine the best predictors
      of CVD and diabetes in Latino/Hispanic patients. A combined effort of health
      influencing and health-governing bodies is needed on all levels to address the
      CVD problem in the Latino/Hispanic population.

PMID- 18059207
TI  - Cardiovascular disease disparities in native Hawaiians.
AB  - Although Hawaii boasts relatively low rates of death from heart disease and
      stroke, past data suggest that Native Hawaiians bear a disproportionate burden of
      mortality from cardiovascular disease (CVD). This study examined 2005-2006 data
      on CVD mortality and risk factors to see if disparities experienced historically
      by Native Hawaiians have continued, increased, or been reduced. Existing data
      were reviewed related to CVD and risk factors for Native Hawaiians in Hawaii and
      compared with statewide and US rates. These data show that Native Hawaiians are
      experiencing continuing and perhaps growing disparities in CVD mortality rates
      and risk factor prevalence. Nevertheless, increased support for enlightened
      social policy and community-directed problem solving can help reduce CVD health
      disparities experienced by Native Hawaiians. Future research should be directed
      at better delineation of the various components of cardiometabolic risk and
      culturally sensitive, and educationally appropriate approaches to CVD risk
      reduction.

PMID- 18059206
TI  - Fatty acid consumption and metabolic syndrome components: the GOCADAN study.
AB  - Fatty acids (FAs) have been related to changes in glucose and lipid metabolism.
      In this article, the authors assess the association between intake of specific
      FAs and components of the metabolic syndrome (MS) in adult Eskimos. A total of
      691 Inupiat Eskimos (325 men and 366 women), aged 34 to 75 years, were examined
      as part of the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN)
      study. The investigation included a physical examination, blood pressure
      measurements, blood sampling under fasting conditions, 2-hour oral glucose
      tolerance test, and a personal interview including a validated food frequency
      questionnaire. Components of MS were defined according to the Third Report of the
      National Cholesterol Education Program Adult Treatment Panel criteria.
      Consumption of individual FAs showed associations with MS components. Long-chain
      omega-3 FAs, from fish and sea mammals, were associated with lower blood
      pressure, serum triglycerides, and 2-hour glucose and higher high-density
      lipoprotein cholesterol, fasting insulin, and homeostasis model assessment.
      Saturated fat consumption was associated with higher triglyceride levels and
      blood pressure. Trans-FA consumption was associated with higher blood pressure.
      Consumption of long-chain omega-3 FAs from marine sources may improve certain MS
      components, and thus may reduce risk for cardiovascular disease. High consumption
      of saturated FAs and trans-FAs may have an adverse effect on MS.

PMID- 18059208
TI  - Androgen excess is associated with insulin resistance and the development of
      diabetes in African American women.
AB  - This study investigated the role of relative androgen excess, designated by low
      sex hormone-binding globulin (SHBG), on development of type 2 diabetes in
      premenopausal African American women. A prospective, longitudinal study was
      conducted on premenopausal African American women, initially aged 36 to 43 years
      (n=119). Patients were reexamined 8 years later to determine whether initial
      androgen status was associated with insulin resistance and development of
      diabetes. Among patients in the low SHBG tertile, 18% converted to type 2
      diabetes by the second examination, as compared with 5% in the mid SHBG tertile
      and 2.5% in the high SHBG tertile (P=.04). Insulin sensitivity was significantly
      different among the 3 tertiles (P<.01). There was no significant difference in
      total cholesterol, high-density lipoprotein, low-density lipoprotein, or
      triglycerides among the SHBG tertiles. This prospective study demonstrates that
      relative androgen excess is associated with insulin resistance and increases the
      risk for development of diabetes in premenopausal African American women.

PMID- 18059209
TI  - The cardiometabolic syndrome in persons of the African diaspora: challenges and
      opportunities.
AB  - Unique genetic traits appear to play a role in the increased rates of
      hypertension (HTN), glucose dysregulation/diabetes (T2DM), and obesity in persons
      of African descent. Indeed, with increasing rates of westernization/urbanization
      and concomitant increases in obesity and T2DM, a similar predisposition to the
      cardiometabolic syndrome and cardiovascular disease (CVD) can be seen in Africans
      compared with persons of African descent, with CVD reaching epidemic proportions
      in many areas of Africa. In addition, the complex relationships of metabolic
      abnormalities that are unique to individuals of African descent have also been
      demonstrated in Africans. These include: (1) a dissociation of HTN to insulin
      resistance; (2) relative favorable lipid profile in the setting of increasing
      rates of CVD; (3) low levels of visceral adiposity in the setting of obesity and
      insulin resistance; and (4) a dissociation of insulin sensitivity and adiponectin
      when compared with Caucasians. Although not well understood, these unique
      relationships suggest that conventional parameters for CVD do not apply to
      Africans of persons of African descent.

PMID- 18059210
TI  - The metabolic syndrome and dyslipidemia among Asian Indians: a population with
      high rates of diabetes and premature coronary artery disease.
AB  - South Asians have high rates of diabetes and the highest rates of premature
      coronary artery disease in the world, both occurring about 10 years earlier than
      in other populations. The metabolic syndrome (MS), which appears to be the
      antecedent or "common soil" for both of these conditions, is also common among
      South Asians. Because South Asians develop metabolic abnormalities at a lower
      body mass index and waist circumference than other groups, conventional criteria
      underestimate the prevalence of MS by 25% to 50%. The proposed South Asian
      Modified National Cholesterol Education Program criteria that use abdominal
      obesity as an optional component and the South Asian-specific waist circumference
      recommended by the International Diabetes Federation appear to be more
      appropriate in this population. Furthermore, Asian Indians have at least double
      the risk of coronary artery disease than that of whites, even when adjusted for
      the presence of diabetes and MS. This increased risk appears to be due to South
      Asian dyslipidemia, which is characterized by high serum levels of apolipoprotein
      B, lipoprotein (a), and triglycerides and low levels of apolipoprotein A1 and
      high-density lipoprotein (HDL) cholesterol. In addition, the HDL particles are
      small, dense, and dysfunctional. MS needs to be recognized as a looming danger to
      South Asians and treated with aggressive lifestyle modifications beginning in
      childhood and at a lower threshold than in other populations.

PMID- 18059211
TI  - The metabolic syndrome in East Asians.
AB  - The metabolic syndrome is an emerging epidemic in developing nations, including
      East Asian countries such as China, Japan, and Korea. Studies examining the
      metabolic syndrome have used different definitions, with prevalence often highly
      dependent on the cut points for abdominal obesity utilized, which have been
      recommended by the International Diabetes Federation to be lower than standards
      used in Caucasians and other ethnic groups. Prevalence rates have generally
      varied from 8% to 13% in men and 2% to 18% in women, depending on ethnic group
      and definition used, and are consistently lower than most Western Caucasian
      populations. While recent dramatic changes in lifestyle from Westernization of
      dietary habits and reduced physical activity present challenges, an emphasis on
      healthful lifestyle changes remains the cornerstone for metabolic syndrome
      management. In addition, clinical management focusing on control of obesity,
      elevated blood pressure, dyslipidemia, and hyperglycemia, with consideration of
      pharmacologic therapy issues unique to certain Asian populations, remains
      important for reducing associated cardiometabolic risks.

PMID- 18059212
TI  - The metabolic syndrome in American Indians: the strong heart study.
AB  - Although the underlying cause of the metabolic syndrome (MS) is not entirely
      clear, it is thought that MS results from central obesity and insulin resistance
      (IR). IR has long been known to be a predictor of type 2 diabetes in many
      populations, including American Indians, the group with a rising prevalence of
      obesity and the highest rate of diabetes in the United States. In addition to
      being a predictor of diabetes, MS has now been shown to be associated with higher
      risk of cardiovascular disease, independent of diabetes, in American Indians as
      well as in other ethnic groups. Furthermore, MS may carry a risk beyond that of
      single risk factors. Identifying MS in American Indians and treating the factors
      that comprise it may reduce risk of both diabetes and cardiovascular disease in
      this population.

PMID- 18059213
TI  - Hypoadiponectinemia as a marker of adipocyte dysfunction--part II: the functional
      significance of low adiponectin secretion.
AB  - Low adiponectin expression is common in obesity and is tightly linked to insulin
      resistance and fat mass expansion. Whereas normal adipocytes offer effective
      metabolic buffering through well-controlled release and uptake of free fatty
      acids on demand, adipocyte expansion induced by caloric excess and modulated by
      genetic, regional, and systemic factors elicits major unfavorable changes in fat
      cell phenotypes. Large, dysfunctional adipocytes show increased lipolysis and
      enhanced expression and secretion of proinflammatory and pro-oxidative cytokines.
      Low adiponectin secretion is a hallmark of impaired adipocyte function; its
      secretion is inhibited by cytokines such as tumor necrosis factor alpha,
      interleukin 6 and plasminogen activator inhibitor 1 and by high oxidative stress
      induced by increased fatty acids that activate nicotinamide adenine dinucleotide
      phosphate-oxidase. The ensuing hypoadiponectinemia may aggravate insulin
      resistance and facilitate the evolution of type 2 diabetes. Only massive weight
      loss allows true and sustained recovery of normal fat cell function as reflected
      by adiponectin secretion.

PMID- 18059214
TI  - Rosiglitazone and cardiovascular risk: weighing recent evidence.

PMID- 18059215
TI  - Thiazolidinediones and diabetic nephropathy: need for a closer examination?
AB  - Diabetic nephropathy is an important public health issue and a major challenge
      for modern nephrology, as it is the primary cause of end-stage renal disease. In
      addition to established risk factors for diabetic nephropathy progression (ie,
      hyperglycemia and hypertension), current knowledge suggests that other factors
      can be involved. Population studies show that insulin resistance and
      hyperinsulinemia are also associated with chronic kidney disease, and several
      background mechanisms could explain this relationship. The hypoglycemic class of
      thiazolidinediones that act through reduction of insulin resistance were found to
      protect against renal injury in diabetic animals and to reduce urinary albumin
      excretion in patients with type 2 diabetes and microalbuminuria. This
      renoprotective action is supported by relevant studies showing that
      thiazolidinediones act beneficially on most of the players involved in diabetic
      nephropathy progression. Recent studies have raised uncertainty about the
      cardiovascular safety of thiazolidinediones. After the latter issue is resolved,
      however, it would appear very interesting to conduct specific studies in patients
      with overt diabetic nephropathy to determine the effect of these agents on
      proteinuria and kidney disease progression.

PMID- 18059216
TI  - New evidence confirms risks associated with prehypertension and benefits of
      therapeutic lifestyle changes in management.
AB  - TJ is a 57-year-old female high school biology teacher who presents for a routine
      checkup. She has a strong family history of heart disease and wants to ensure
      that she does everything possible to keep her risk low. TJ is postmenopausal and
      stopped hormone replacement therapy 3 years ago. Physical examination is
      unremarkable other than the fact that the patient is overweight, with a body mass
      index of 29.2 kg/m2, and her blood pressure (BP) is 132/84 mm Hg. Her fasting
      plasma glucose level is 103 mg/dL, high-density lipoprotein cholesterol level 38
      mg/dL, and triglyceride level 165 mg/dL. Based on her BP and concurrent
      cardiometabolic syndrome, what do you tell her about the risks associated with
      her BP, and how do you approach her management?

PMID- 18059217
TI  - Intraventricular mechanical asynchrony in asymptomatic morbidly obese
      individuals.

PMID- 18059218
TI  - "Seedling" mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas)
      are common incidental tumors of the esophagogastric junction.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common nonepithelial
      neoplasm of the gastrointestinal tract and show a predilection for the stomach.
      Most are detected because of symptoms, but some are incidental findings at
      autopsy or surgery for other reasons. Incidental GISTs tend to be smaller at
      diagnosis, but even small (<1 cm) GISTs have been shown to harbor activating KIT
      mutations at rates similar to advanced GISTs. However, the prevalence and
      characteristics of small GISTs in surgical resections of the esophagogastric
      junction (EGJ) remains unclear. We studied 150 esophagogastric resections for
      esophageal or EGJ carcinomas (100 with preoperative chemoradiation and 50
      untreated cases) that had been extensively embedded for histologic examination
      (mean 30 sections/case). Number, size, morphology, and location of all GISTs and
      leiomyomas were recorded. All potential GISTs were evaluated with CD117 and CD34
      immunohistochemistry, and a subset (35) leiomyomas with smooth muscle actin,
      desmin, and CD117. We found 18 incidental GISTs in 15 of 150 (10%) patients; 3
      patients harbored 2 separate lesions. Prevalence of GIST was identical in treated
      (10 of 100) and untreated (5 of 50) cases. All (100%) showed positivity for both
      CD117 and CD34 and all were of spindle cell morphology. Lesions ranged from 0.2
      to 3.0 mm in size (mean 1.3 mm). Eight (44%) were based in the outer muscularis
      propria, 7 (39%) in inner muscularis, and 3 (17%) between the muscle layers. The
      lesions tended to cluster near the EGJ, with 8 (44%) on the gastric side, 9 (50%)
      on the esophageal side, and 1 (6%) undetermined owing to overlying ulceration.
      Leiomyomas were even more common than GIST, occurring in 47% of patients (44% of
      treated and 52% of untreated, P=0.39), with a mean of 3 leiomyomas per patient
      (range 1 to 13) and mean size of 1.7 mm (range 0.2 to 12 mm). Unlike colorectal
      leiomyomas, most (91%) EGJ leiomyomas were located in the inner muscularis
      propria and only rarely (1%) in muscularis mucosa. These results suggest that
      GIST and leiomyoma are common incidental "seedling" lesions of the EGJ, found in
      10% and 47% of patients undergoing surgery for esophageal carcinoma. The common
      occurrence of microscopic GISTs compared with the rarity of clinically manifest
      and malignant esophagogastric GISTs suggests that additional genetic or
      epigenetic alterations must happen for neoplastic progression.

PMID- 18059219
TI  - Detail histologic analysis of nerve plexus invasion in invasive ductal carcinoma
      of the pancreas and its prognostic impact.
AB  - Nerve plexus invasion is regarded as one of the most important prognostic factors
      in invasive ductal carcinoma (IDC) of the pancreas, though nerve plexus invasion
      has not been evaluated in terms of prognostic impact on the basis of detailed
      histologic investigation. The purpose of this study was to precisely examine
      morphologic characteristics of nerve plexus invasion and analyze its prognostic
      predictive power compared with the well-known prognostic parameters of pancreatic
      IDCs. The outcome and histologic features of 75 patients with pancreatic IDC in
      the pancreas head were investigated, and 422 lesions of nerve plexus invasion
      were evaluated. Tumor cells invading nerve plexus showed a duct-forming
      differentiated feature and predominantly existed in the perineurium and
      perineural space. Multivariate analyses revealed that the important prognostic
      factors, in addition to invasive tumor size and tumor necrosis, were at long
      distances from nerve plexus invasion to pancreatic capsule and perineural
      invasion in nerve plexus invasion.

PMID- 18059220
TI  - Differential expression of hormonal and growth factor receptors in salivary duct
      carcinomas: biologic significance and potential role in therapeutic
      stratification of patients.
AB  - Salivary duct carcinoma (SDC), a rare malignancy, manifests remarkable
      morphologic and biologic resemblance to high-grade mammary ductal carcinoma. We
      contend that, similar to mammary ductal carcinoma, hormones and growth factors
      may play a role in SDCs. Our aim was to determine the incidence and clinical
      significance of the expression of several hormone and growth factor receptors and
      evaluate their potential in therapeutic stratification of SDC patients in the
      largest cohort studied to date. Eighty-four archived tumor tissue blocks were
      analyzed immunohistochemically for expression of estrogen receptor-beta (ERbeta),
      androgen receptor (AR), and proline, glutamic acid, and leucine-rich protein-1
      and growth factor receptors HER-2 and epidermal growth factor receptor. The
      results were correlated with available pathologic, demographic, and clinical data
      from 59 of 84 cases. Proline, glutamic acid, and leucine-rich protein-1, ERbeta,
      and AR were expressed individually in 94% (71/76), 73% (57/80), and 67% (56/84)
      of SDCs, respectively, and coexpressed in 45% (34/75). AR was expressed
      significantly more often in SDCs of men than in SDCs of women [79% (35/57) vs.
      33% (9/27), P<0.001]. Epidermal growth factor receptor and HER-2 were
      overexpressed individually in 48% (40/83) and 25% (21/84), respectively, and co
      overexpressed in 12% (10/83). Survival decreased significantly in patients with
      lymph node metastasis (P=0.002) and positive surgical margins (P=0.006). Lack of
      ERbeta expression correlated with increased local and regional recurrence (P=0.05
      and P=0.002, respectively). Together, these results indicate that (a) ERbeta down
      regulation is associated with adverse clinical features, (b) lymph node and
      surgical margin status are significant survival factors, and (c) the differential
      expression of these hormones and growth factor receptors may assist in triaging
      patients with SDC for novel therapies.

PMID- 18059221
TI  - Prognostic features of surgical stage I uterine carcinosarcoma.
AB  - Uterine carcinosarcomas (CSs) are aggressive neoplasms, with 5-year overall
      survival (OS) rates of less than 35%. They are customarily separated into types
      harboring either heterologous or homologous mesenchymal elements, but the
      prognostic significance of this finding is controversial. Our goal was to study
      clinicopathologic features of possible prognostic relevance in surgical stage I
      uterine CS. A retrospective clinical and histopathologic review was performed for
      all women diagnosed with surgical stage I uterine CS. These tumors were compared
      with stage I high-grade endometrial (HGEm) carcinomas for clinical outcomes.
      There were 42 cases of surgical stage I uterine CS identified between January
      1990 and January 2004. The disease-free survival and OS rates for patients with
      stage I CS were significantly worse compared with stage I HGEm (P=0.001; P=0.01).
      The median disease-free survival for patients with heterologous CS was 15 months
      and had not been reached for women with homologous CS (P=0.001). The 3-year OS
      rates were 45% versus 93% in women with heterologous compared with homologous
      stage I CS (P<0.001). The 3-year OS rates for homologous CS and HGEm were both
      >90%. Homologous stage I CSs have survival outcomes that are similar to HGEm.
      This further supports the concept that homologous stage I CSs are carcinomas with
      sarcomatoid features, not sarcomas. More importantly, the presence of
      heterologous sarcomatous elements is a powerful negative prognostic factor in
      surgical stage I uterine CS.

PMID- 18059222
TI  - Juxtacortical chondromyxoid fibroma of bone: a unique variant: a case study of 20
      patients.
AB  - BACKGROUND: Chondromyxoid fibroma (CMF) is a rare neoplasm of the appendicular
      skeleton of young adults. We report 20 cases of a poorly recognized subtype which
      arises on the surface of long bones and erodes the cortical surface causing a
      periosteal reaction. This entity should be included in the differential diagnosis
      of bone surface lesions as it may be mistaken for a more aggressive neoplasm.
      DESIGN: A retrospective review at the Mayo Clinic identified 259 CMF cases, 13 of
      which were parosteal. Additionally, 2 cases were diagnosed at the University of
      Alabama at Birmingham and 5 cases were from one of our authors' files. We
      reviewed the clinical radiographic and pathologic findings of all 20 cases.
      RESULTS: Juxtacortical CMF occurred over a large age range (12 to 82 y) with a
      median age of 40.2 years. A slight male predilection (5:4) was seen. The most
      common presentation was bone pain. All 20 cases showed solitary, radiolucent
      surface lesions with sclerotic margins and extension into the overlying soft
      tissues. Most of the lesions were in the proximal tibial metaphysis.
      Histologically, the tumors had characteristic features of CMF. Several cases
      contained distinctive areas of calcification, which is not a feature of
      conventional CMF. Eleven of 12 cases were cured with simple excision. CONCLUSION:
      CMF should be included in the differential diagnosis of bone surface lesions. The
      clinical and radiologic findings must be known. The morphology of this lesion is
      similar to conventional CMF with the exception of focal exuberant calcification.
      Conservative therapy is the treatment of choice.

PMID- 18059223
TI  - Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for
      systemic mastocytosis.
AB  - Systemic mastocytosis (SM) is characterized by the accumulation of neoplastic
      mast cells in bone marrow and other organs. Gastrointestinal (GI) symptoms are
      common in both SM and cutaneous mastocytosis [urticaria pigmentosa (UP)], and are
      usually caused by the release of histamine and other inflammatory mediators.
      Occasionally, neoplastic mast cells may also directly infiltrate the GI tract.
      Previous studies have suggested that enumeration of the mast cells in GI biopsies
      may help establish the diagnosis of SM. However, mast cells have been reported to
      be increased in various inflammatory diseases, and mast cell density has not been
      systematically evaluated in other GI disorders. Recently, expression of CD25 by
      mast cells in bone marrow has been shown to be specific for SM. The purpose of
      this study was (1) to quantitate and compare mast cells in mucosal biopsies from
      patients with SM involving the GI tract, UP with GI symptoms, and a control group
      of diverse inflammatory disorders, and (2) to determine whether immunostaining
      for CD25 can be used to distinguish neoplastic from reactive mast cells in GI
      biopsies. Seventeen GI biopsies from 6 patients with SM; 17 GI biopsies from 5
      patients with UP; and 157 control cases including 10 each normal stomach,
      duodenum, terminal ileum, and colon, Helicobacter pylori gastritis, bile reflux
      gastropathy, peptic duodenitis, celiac disease, Crohn disease, ulcerative
      colitis, lymphocytic colitis, and collagenous colitis, 20 biopsies from 16
      patients with irritable bowel syndrome, 8 biopsies from 5 patients with parasitic
      infections, and 9 biopsies from 7 patients with eosinophilic gastroenteritis were
      immunostained for mast cell tryptase, c-kit (CD117), and CD25. Mucosal mast cells
      were quantitated, and the presence or absence of CD25 expression on mast cells
      was determined. In SM patients, mast cells in the small intestine and colon
      numbered >100/high-power field (HPF) in nearly all cases (mean 196/HPF; range 74
      to 339). This was significantly higher than in GI biopsies from UP patients (mean
      17/HPF; range 8 to 32, P<0.0001) and all inflammatory diseases (P<0.01). Mast
      cell density in other disorders ranged from a mean of 12/HPF in H. pylori
      gastritis to 47/HPF in parasitic infections. Interestingly, all SM biopsies (and
      none of the other cases) contained aggregates or confluent sheets of mast cells.
      In addition, mast cells in all SM cases were positive for CD25, whereas GI
      mucosal mast cells in UP and all other control cases were negative. In
      conclusion, quantitation of mast cells can be helpful to diagnose SM in GI
      mucosal biopsies, although mast cells are also markedly increased in parasitic
      infections. Aggregates or sheets of mast cells are only seen in SM.
      Immunoreactivity for CD25 in GI mucosal mast cells is specific for SM and can be
      used to confirm the diagnosis.

PMID- 18059224
TI  - WHO 2004 criteria and CK19 are reliable prognostic markers in pancreatic
      endocrine tumors.
AB  - BACKGROUND: It is difficult to predict the biologic behavior of pancreatic
      endocrine tumors in absence of metastases or invasion into adjacent organs. The
      World Health Organization (WHO) has proposed in 2004 size, angioinvasion, mitotic
      activity, and MIB1 proliferation index as prognostic criteria. Our aim was to
      test retrospectively the predictive value of these 2004 WHO criteria and of CK19,
      CD99, COX2, and p27 immunohistochemistry in a large series of patients with long
      term follow-up. DESIGN: The histology of 216 pancreatic endocrine tumor specimens
      was reviewed and the tumors were reclassified according to the 2004 WHO
      classification. The prognostic value of the WHO classification and the
      histopathologic criteria necrosis and nodular fibrosis was tested in 113
      patients. A tissue microarray was constructed for immunohistochemical staining.
      The staining results were scored quantitatively for MIB1 and semiquantitatively
      for CK19, COX2, p27, and CD99. The prognostic value of these markers was tested
      in 93 patients. RESULTS: The stratification of the patients into 4 risk groups
      according to the 2004 WHO classification was reliable with regard to both time
      span to relapse and tumor-specific death. In a multivariate analysis, the CK19
      status was shown to be independent of the WHO criteria. By contrast, the
      prognostic significance of COX2, p27, and CD99 could not be confirmed.
      CONCLUSIONS: The 2004 WHO classification with 4 risk groups is very reliable for
      predicting both disease-free survival and the time span until tumor-specific
      death. CK19 staining is a potential additional prognostic marker independent from
      the WHO criteria for pancreatic endocrine tumors.

PMID- 18059225
TI  - Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and
      a review of the literature.
AB  - High-grade transformation of adenoid cystic carcinoma (ACC) (previously referred
      to as dedifferentiation) is a rare phenomenon that does not fit into the
      traditional ACC grading schemes. The importance and minimal criteria for
      distinction from solid (grade III) ACC are not well established. We report 11 new
      cases and review the literature to further define the profile of this tumor. The
      median age was 61 years (range: 32 to 72 y) with a male predominance (male to
      female ratio of 1.75:1). The most commonly involved sites were sinonasal (4/11)
      and submandibular (4/11). Lymph nodes were pathologically positive in 4/7 (57.1%)
      cases. Distant metastases to the lung (n=2) and soft tissue of the shoulder (n=1)
      were observed. Five of 9 patients (55.6%) died, all within 5 years with a median
      overall survival of 12 months. Histologically, ACC with high-grade transformation
      was distinguished from conventional ACC by nuclear enlargement and irregularity,
      higher mitotic counts, and the loss of the biphasic ductal-myoepithelial
      differentiation. Useful supportive criteria were prominent comedonecrosis and
      fibrocellular desmoplasia. The most common morphologies for the high-grade
      component were poorly differentiated cribriform adenocarcinoma and solid
      undifferentiated carcinoma. Micropapillary and squamoid patterns were
      occasionally present. Ki-67 and p53 labeling indices were elevated in the high
      grade components, though c-kit and cyclin-D1 were not. ACC-high-grade
      transformation is a highly aggressive salivary gland tumor with a variety of
      histologic patterns. The high propensity for lymph node metastases suggests a
      role for neck dissection in patients with this rare tumor.

PMID- 18059226
TI  - c-Maf expression in angioimmunoblastic T-cell lymphoma.
AB  - The oncogene c-Maf was recently found to be overexpressed in approximately 50% of
      multiple myeloma cases, and a role for c-Maf in promoting cyclin D2 expression
      has been postulated. We previously examined c-Maf expression in various T-cell
      lymphomas by reverse-transcription polymerase chain reaction and found extremely
      elevated c-Maf levels in angioimmunoblastic T-cell lymphoma (AILT). In this
      study, we examined T-cell lymphomas for c-Maf and cyclin expression
      immunohistochemically. Of 93 cases of T-cell lymphomas we investigated in the
      current study, c-Maf expression was seen in 23 out of 31 cases of AILT, 3 out of
      11 of adult T-cell leukemia/lymphoma, 4 out of 19 of peripheral T-cell lymphoma,
      unspecified [PTCL(U)], and 0 out of 11 cases of mycosis fungoides, 0 out of 11 of
      anaplastic large cell lymphoma, and 1 out of 10 of extranodal NK/T-cell lymphoma,
      nasal type. Double immunostaining in AILT revealed that the majority of c-Maf
      positive cells were also positive for CD43 (MT1), CD45RO (UCHL-1), and CD4 but
      were negative for CD20 (L26). Additionally, cyclins D1 and D2, which stimulate
      cell cycle progression, were overexpressed in a large number of the c-Maf
      positive AILT samples. Quantitative reverse-transcription polymerase chain
      reaction analysis also showed that c-Maf was overexpressed in 8/31 cases of AILT,
      0/19 cases of PTCL(U), 0/11 cases of anaplastic large cell lymphoma, 0/10 cases
      of extranodal NK/T-cell lymphoma, nasal type, and 2/8 cases of multiple myeloma,
      presenting significant difference between AILT and PTCL(U) (P=0.016, chi test).
      These findings strongly suggest that CD4-positive neoplastic T cells in AILT show
      c-Maf expression and provide new insight into the pathogenesis of AILT suggesting
      c-Maf to be a useful diagnostic marker for AILT.

PMID- 18059227
TI  - Non-neoplastic renal diseases are often unrecognized in adult tumor nephrectomy
      specimens: a review of 246 cases.
AB  - The pathologic evaluation of tumor nephrectomy specimens focuses on the
      diagnosis, grading, and staging of the neoplasm. The presence of coincidental non
      neoplastic diseases in these specimens may have significant implications for
      patient outcomes. The purpose of this study is to determine the spectrum of non
      neoplastic disease processes that may be overlooked in tumor nephrectomies, and
      to ascertain the extent to which surgical pathologists are trained to recognize
      these lesions. We reviewed the hematoxylin and eosin-stained slides of 246 adult
      tumor nephrectomy specimens with an emphasis on the non-neoplastic renal
      parenchyma. Further analysis of cases with pathologic alterations included
      special stains and direct immunofluorescence microscopy. The surgical pathology
      reports were reviewed to determine whether the non-neoplastic lesions were
      originally identified. We also surveyed United States pathology residency
      programs to determine how many require training in medical renal pathology. Forty
      one cases (16.7%) had alterations, such as diffuse and/or nodular mesangial
      sclerosis, mesangial hypercellularity, or glomerular basement membrane thickening
      that warranted further study. After further work-up and clinical correlation, the
      pathologic changes in 24 cases were categorized as follows: diabetic nephropathy
      (19 cases) of which one demonstrated atheroembolic disease, thrombotic
      microangiopathy (3 cases), sickle cell nephropathy (1 case), and focal segmental
      glomerulosclerosis (1 case). Twenty-one (88%) of these diagnoses were not
      identified at initial pathologic evaluation. Only 35 of 98 pathology residency
      programs that responded to our survey require any formal training in medical
      renal pathology. Although accurate pathologic evaluation of renal neoplasms
      remains essential, surgical pathologists should be aware that coincidental non
      neoplastic renal diseases are common, often not recognized, and may have
      important implications for patient care. Further consideration should be given to
      the training requirements of pathology residents and the guidelines for
      evaluation of nephrectomy specimens to avoid missing non-neoplastic renal
      lesions.

PMID- 18059228
TI  - Angiocentric glioma: report of clinico-pathologic and genetic findings in 8
      cases.
AB  - Angiocentric glioma has recently been described as a novel epilepsy associated
      tumor with distinct clinico-pathologic features. We report the clinical and
      pathologic findings in 8 additional cases of this rare tumor type and extend its
      characterization by genomic profiling. Almost all patients had a history of long
      standing drug-resistant epilepsy. Cortico-subcortical tumors were located in the
      temporal and parietal lobes. Seizures began at 3 to 14 years of age and surgery
      was performed at 6 to 70 years. Histologically, the tumors were characterized by
      diffuse growth and prominent perivascular tumor cell arrangements with features
      of astrocytic/ependymal differentiation, but lacking neoplastic neuronal
      features. Necrosis and vascular proliferation were not observed and mitoses were
      sparse or absent. MIB-1 proliferation indices ranged from <1% to 5%.
      Immunohistochemically, all cases stained positively for glial fibrillary acidic
      protein, vimentin, protein S100B, variably for podoplanin, and showed epithelial
      membrane antigen-positive cytoplasmic dots. Electron microscopy showed ependymal
      characteristics in 2 of 3 cases investigated. An analysis of genomic imbalances
      by chromosomal comparative genomic hybridization revealed loss of chromosomal
      bands 6q24 to q25 as the only alteration in 1 of 8 cases. In 1 of 3 cases, a high
      resolution screen by array-comparative genomic hybridization identified a copy
      number gain of 2 adjacent clones from chromosomal band 11p11.2 containing the
      protein-tyrosine phosphatase receptor type J (PTPRJ) gene. All patients are
      seizure free and without evidence of tumor recurrence at follow-up times ranging
      from 1/2 to 6.9 years. Our findings support 2 previous reports proposing that
      angiocentric glioma is a novel glial tumor entity of low-grade malignancy.

PMID- 18059229
TI  - Duplication of the muscularis mucosae in Barrett esophagus: an underrecognized
      feature and its implication for staging of adenocarcinoma.
AB  - Depth of invasion is one of the most important prognostic indicators in
      esophageal adenocarcinoma. Unlike other regions of the gastrointestinal tract,
      the esophagus in Barrett metaplasia frequently develops duplication of the
      muscularis mucosae (MM), but this feature is underrecognized, and its effect on
      appropriate staging of superficially invasive adenocarcinoma is unclear. We first
      randomly selected 50 esophageal resections for high-grade dysplasia or T1
      adenocarcinoma in Barrett esophagus (BE) to evaluate the sensitivity and
      specificity of MM duplication for BE and its histologic characteristics,
      including percentage of the Barrett segment involved by MM duplication, origin of
      the duplicated muscle layer, and appearance of the tissue between duplicated MM.
      Twenty esophageal resections for squamous cell carcinoma served as controls.
      Next, to study the clinical significance of MM duplication, we evaluated 30
      resections for BE that had superficial adenocarcinoma confined to regions of
      duplicated MM. Each case was classified as: depth of invasion (inner MM, space
      between duplicated MM, or outer MM), angiolymphatic invasion, and rate of lymph
      node metastasis. We observed MM duplication in 46 of 50 (92%) BE resections,
      involving 5% to >90% of the Barrett segment, in contrast to none in 20 (0%)
      resected squamous cell carcinoma, P<0.0001. In 5 (10%) cases, the MM was focally
      triplicated. The outer MM was continuous with the single MM beneath squamous
      epithelium, suggesting that outer MM represents the "original" muscle layer. The
      space between duplicated MM predominantly consisted of loose fibrovascular tissue
      similar to submucosa; in 15 (30%) cases, there were also areas of fibrosis or
      thin muscle strands joining the 2 MM layers. Of 30 adenocarcinomas invading
      duplicated MM, 10 (33%) invaded only inner MM, 12 (40%) invaded the space between
      MM, and 8 (27%) invaded the outer MM. Angiolymphatic invasion was present in 5
      (17%) cases, and nodal metastases in 3 (10%, 1 case each of invasion into inner
      MM, between MM, and outer MM). These data show that MM duplication is a
      characteristic finding in BE, but it can pose difficulty in proper staging of
      superficial adenocarcinomas. The 17% rate of angiolymphatic invasion and 10% rate
      of lymph node metastases in our patients with invasion into duplicated MM suggest
      that these tumors can behave aggressively despite their technically intramucosal
      location.

PMID- 18059230
TI  - Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis and in
      elucidating pathogenesis.
AB  - Choriocarcinoma is traditionally described as being composed of cytotrophoblast
      and syncytiotrophoblast. Microscopically, these 2 types of cells are intimately
      associated with each other, forming a characteristic biphasic plexiform pattern,
      however, the nature of these 2 types of trophoblastic cells is not well
      understood. In this study, we used immunohistochemistry for several trophoblastic
      markers to analyze the trophoblastic subpopulations in 36 gestational
      choriocarcinomas. Eighty-one specimens including placenta, complete mole,
      placental site nodule, epithelioid trophoblastic tumor, and placental site
      trophoblastic tumor were analyzed. The antibodies included Mel-CAM, HLA-G, MUC-4,
      and beta-catenin. A semiquantitative assessment of positive cells and the
      cellular localization of these markers were recorded. We found diffuse strong
      membranous and cytoplasmic staining for MUC-4 in mononucleate cells in all 36
      cases (100%) and a similar pattern of localization in 28 cases (78%) for HLA-G.
      This distribution was similar to that in normal placentas, where MUC-4 and HLA-G
      are expressed in the trophoblastic cells of the trophoblastic columns and
      implantation site. In choriocarcinoma, mononucleate trophoblastic cells showed
      moderate immunoreactivity for Mel-CAM, a specific marker for implantation site
      intermediate trophoblast, in 78% of the cases. The MUC-4, HLA-G, and Mel-CAM
      positive trophoblastic cells were larger than cytotrophoblastic cells, with more
      abundant cytoplasm, consistent with the morphology of intermediate trophoblast.
      In contrast, 31% of the choriocarcinomas contained a very small proportion (<5%)
      of mononucleate trophoblastic cells compatible with cytotrophoblast that was
      positive for nuclear beta-catenin, a cytotrophoblast-associated marker. These
      results suggest that choriocarcinoma is composed predominantly of a mixture of
      syncytiotrophoblast and intermediate trophoblast with only a small proportion of
      cytotrophoblast. The presence of nuclear beta-catenin staining in the
      cytotrophoblast of choriocarcinoma is consistent with the view that
      choriocarcinoma develops from transformed cytotrophoblastic cells which are
      presumably the cancer stem cells that differentiate into either intermediate
      trophoblast or syncytiotrophoblast.

PMID- 18059231
TI  - Morphologic features are useful in distinguishing Barrett esophagus from carditis
      with intestinal metaplasia.
AB  - Barrett esophagus (BE) and carditis with intestinal metaplasia (CIM) differ in
      their risk of malignancy and implications for patient management, but are
      difficult to distinguish in mucosal biopsies from the gastroesophageal junction
      region. The present study was performed to evaluate the role of routine
      morphology in distinguishing BE from CIM in mucosal biopsies and to assess the
      degree of interobserver variability in recognizing morphologic parameters that
      are of significance in making this distinction. Several morphologic features,
      including presence of crypt disarray and atrophy, incomplete and diffuse
      intestinal metaplasia, multilayered epithelium, squamous epithelium overlying
      columnar crypts with intestinal metaplasia, hybrid glands, and esophageal
      glands/ducts, were significantly associated with a diagnosis of BE. The latter 3
      features were observed exclusively in BE biopsies. Furthermore, multiple BE
      associated morphologic features were often present together in BE but not CIM
      biopsies. There was substantial agreement (kappa=0.6) among expert
      gastrointestinal pathologists for distinguishing BE from CIM even in the absence
      of clinical/endoscopic information. The interobserver agreement in recognition of
      BE-associated morphologic features ranged from almost perfect for some features
      like esophageal glands/ducts (kappa=0.83) to slight for multilayered epithelium
      (kappa=0.17). In conclusion, our findings indicate that several morphologic
      features are helpful in distinguishing BE from CIM. The combined presence of
      multiple BE-associated morphologic features can be used in making this
      distinction with a high degree of accuracy. Larger prospective studies need to be
      performed to validate these findings and evaluate the reproducibility of this
      approach in routine clinical practice.

PMID- 18059232
TI  - A comprehensive study of nondysplastic and dysplastic serrated polyps of the
      vermiform appendix.
AB  - Serrated colorectal polyps often show DNA hypermethylation and/or BRAF mutations
      and have been implicated in the "serrated neoplastic pathway." Although similar
      lesions occur in the appendix, they have never been systematically investigated.
      We evaluated a study group of 56 serrated polyps, a control group of 17 mucinous
      cystadenomas, and 4 adenocarcinomas with adjacent serrated polyps of the appendix
      to better understand their pathogenesis. The study cases were classified as
      nondysplastic or dysplastic serrated polyps and evaluated for MLH-1, MSH-2, MGMT,
      beta-catenin, p53, and Ki-67 expression, BRAF and KRAS mutations, and
      microsatellite instability. Serrated polyps usually occurred in older adults with
      no sex predilection. Most (59%) lacked dysplasia, but all showed similar
      molecular features, regardless of the degree of dysplasia present. Decreased MLH
      1 (50%, P<0.001) and/or MGMT (59%, P<0.001) expression and BRAF (29%, P=0.007)
      mutations were significantly more common in serrated polyps, but BRAF mutations
      were detected in a minority of the extracted DNA in 15/16 cases. Of the 28 cases
      with decreased MLH-1 expression, none showed high-frequency microsatellite
      instability. Loss of MLH-1 (25%) or MGMT (50%) expression and BRAF or KRAS
      mutations (50%) were inconsistently present in adenocarcinomas and were not
      identified in combination in any cases. We conclude that molecular features of
      the "serrated neoplastic pathway" are present with similar frequencies among
      dysplastic and nondysplastic serrated appendiceal polyps and are not highly
      prevalent in adjacent carcinomas. These features, including BRAF mutations, may
      be more closely related to a serrated morphology in appendiceal polyps rather
      than biologically important changes.

PMID- 18059233
TI  - Histology of symptomatic acute hepatitis C infection in immunocompetent adults.
AB  - Acute hepatitis C in immunocompetent individuals is rarely symptomatic and rarely
      biopsied. Thus, the histologic descriptions of acute hepatitis C remain limited.
      The histology of 5 cases of acute hepatitis C in adults were studied by selecting
      cases from the consult and surgical pathology files of a single institution. The
      5 individuals, 3 males and 2 females, had an average age at biopsy of 50+/-17
      years. They presented with jaundice and other nonspecific abdominal symptoms. The
      time interval from clinical presentation to biopsy ranged from 2 to 18 weeks. The
      average alanine aminotransferase/aspartate aminotransferase/alkaline phosphatase
      at the time of biopsy was 308/73/85 U/L. The average total bilirubin was 5.2
      mg/dL. Each individual had a single liver biopsy. The histologic findings of the
      2 cases biopsied in close temporal proximity to the initial clinical presentation
      showed similar histologic findings of mixed portal infiltrates with lymphocytes
      and neutrophils along with bile ductular proliferation that raised the
      possibility of down stream biliary tract disease. The lobules showed canalicular
      cholestasis and mild to moderate inflammation. In the third and fourth case,
      obtained 8 weeks after presentation, the biopsies showed mild to moderate portal
      and lobular lymphocytic inflammation, findings that were also present in the last
      case, obtained 18 weeks after presentation. In conclusion, early after acute
      hepatitis C viral infection, biopsies can have a cholestatic pattern whereas
      later biopsies tend to show mild nonspecific portal and lobular lymphocytic
      inflammation. Proper histologic diagnosis can be aided by an awareness of the
      various histologic findings, which vary depending on the time interval from
      clinical symptoms to biopsy.

PMID- 18059234
TI  - Thyroid transcription factor-1 expression in endometrial and endocervical
      adenocarcinomas.
AB  - Thyroid transcription factor-1 (TTF-1) is widely used in the diagnosis of lung
      and thyroid carcinomas. Although there have been reports of TTF-1
      immunoreactivity in tumors other than those originating in the lung or thyroid,
      endocervical and endometrial adenocarcinomas have not been studied in large
      numbers. Our study provides data regarding the incidence and distribution of TTF
      1 expression in these tumors. Twenty-eight endocervical (9 well, 12 moderately,
      and 7 poorly differentiated), 32 endometrioid endometrial adenocarcinomas (11
      grade I, 8 grade II, and 13 grade III), and 13 uterine serous carcinomas were
      retrieved and stained with TTF-1. None of the tumors had a neuroendocrine
      component. The hematoxylin and eosin and anti-TTF-1 antibody stained sections
      were reviewed, and the presence and distribution of TTF-1 nuclear positivity was
      recorded. A semiquantitative grading system used to evaluate the distribution of
      TTF-1 staining (0 = negative, 1+ = <5%, 2+ = 5% to 25%, 3+ = 26% to 50%, 4+ = 51%
      to 75%, and 5+ = >75%). TTF-1 expression was seen in 1 of 28 (4%) of the
      endocervical adenocarcinomas and this was 4+ in distribution. The positive
      endocervical carcinoma was poorly differentiated. TTF-1 expression was present in
      6 of 32 (19%) of the endometrioid adenocarcinomas (1 grade I, 2 grade II, and 3
      grade III) and varied from 1+ to 4+ in distribution. Only 2 of 32 (6%) of the
      endometrioid adenocarcinomas stained diffusely (4+). There was no apparent
      correlation between the degree of differentiation and TTF-1 positivity in the
      adenocarcinomas. Three of 13 (23%) serous carcinomas were also positive (1 case
      5+ and 2 cases 1+). Although TTF-1 is generally considered to be a relatively
      specific marker for lung and thyroid neoplasms, the occasional expression of
      endometrial and endocervical carcinomas should be kept in mind when evaluating
      neoplasms of uncertain origin. It should also be taken into consideration in the
      evaluation of adenocarcinomas involving the lung in patients with a history of a
      gynecologic malignancy.

PMID- 18059236
TI  - Polymorphous low grade adenocarcinoma: review and case report.
AB  - Polymorphous Low-Grade Adenocarcinoma is a rare, malignant salivary gland tumor,
      which is found almost exclusively in minor salivary glands. It is more frequent
      in the age range from 30 to 70, with a clear female predilection in a 2:1 ratio.
      It is usually located in the hard or soft palate, although it may be found in the
      rest of the oral cavity too. It is rare in major salivary glands. In general it
      has good prognosis, with recurrence rates in the range of 17% - 24%. Although
      rare, metastasis to regional lymph nodes may occur in 9% of the cases. This
      report describes the case of a patient that consulted at the Military
      Odontological Center (Central Odontologica del Ejercito) due to an esthetic
      alteration of her dental prosthesis, which had been made 8 years before. The
      patient was sent to the Maxillofacial Surgery Service, where the intraoral
      examination showed a big mass compromising the hard palate and the alveolar
      ridge. During examination, a dent in her prosthesis was found to correspond to
      the tumor mass; it was therefore concluded that the tumor had at least an eight
      year-old evolution. An incisional biopsy was carried out, and once the
      polymorphous low-grade adenocarcinoma diagnosis had been stated, the patient was
      sent to the Head and Neck Surgery Service of the Military Hospital, where the
      lesion was treated by wide surgical excision followed by radiation therapy.

PMID- 18059235
TI  - Loss of expression of protein kinase a regulatory subunit 1alpha in pigmented
      epithelioid melanocytoma but not in melanoma or other melanocytic lesions.
AB  - Pigmented epithelioid melanocytoma (PEM) is a recently described entity
      comprising most cases previously described as "animal-type melanoma" and
      epithelioid blue nevus (EBN) occurring in patients with the multiple neoplasia
      syndrome Carney complex (CNC). Mutations of the protein kinase A regulatory
      subunit type 1alpha (R1alpha) (coded by the PRKAR1A gene) are found in more than
      half of CNC patients. In this study, we investigated whether PEM and EBN are
      related at the molecular level, and whether changes in the PRKAR1A gene status
      and the expression of the R1alpha protein may be involved in the pathogenesis of
      PEM and other melanocytic lesions. Histologic analysis of hematoxylin and eosin
      stained sections and immunohistochemistry (IHC) with R1alpha antibody were
      performed on 34 sporadic PEMs, 8 CNC-associated PEMs from patients with known
      PRKAR1A mutations, 297 benign and malignant melanocytic tumors (127 conventional
      sections of 10 compound nevi, 10 Spitz nevi, 5 deep-penetrating nevi, 5 blue
      nevi, 6 cellular blue nevi, 2 malignant blue nevi, 3 lentigo maligna, and 86
      melanomas of various types); in addition, 170 tissue microarray sections
      consisting of 35 benign nevi, 60 primary melanomas, and 75 metastatic melanomas,
      and 5 equine dermal melanomas, were examined. Histologic diagnoses were based on
      preexisting pathologic reports and were confirmed for this study. DNA studies
      [loss of heterozygosity (LOH) for the 17q22-24 locus and the PRKAR1A gene
      sequencing] were performed on 60 melanomas and 7 PEMs. IHC showed that R1alpha
      was expressed in all but one core from tissue microarrays (169/170), and in all
      127 melanocytic lesions evaluated in conventional sections. By contrast, R1alpha
      was not expressed in the 8 EBN from patients with CNC and PRKAR1A mutations.
      Expression of R1alpha was lost in 28 of 34 PEMs (82%). R1alpha was expressed in
      the 5 equine melanomas studied. DNA studies correlated with IHC findings: there
      were no PRKAR1A mutations in any of the melanomas studied and the rate of LOH for
      17q22-24 was less than 7%; 5 of the 7 PEMs showed extensive 17q22-24 LOH but no
      PRKAR1A mutations. The results support the concept that PEM is a distinct
      melanocytic tumor occurring in a sporadic setting and in the context of CNC. They
      also suggest that PEM differs from melanomas in equine melanotic disease, further
      arguing that the term animal-type melanoma may be a misnomer for this group of
      lesions. Loss of expression of R1alpha offers a useful diagnostic test that helps
      to distinguish PEM from lesions that mimic it histologically.

PMID- 18059237
TI  - Plasmacytoid myoepithelioma of the palate. Report of one case and review of the
      literature.
AB  - INTRODUCTION: Myoepithelioma is a benign neoplasm of salivary glands, represents
      1.5 % of all salivary glands neoplasm. The plasmacytoid myoepithelioma from
      palate salivary glands is considered as a rare entity, at date it has been
      reported 14 cases. It is present one case of plasmacytoid myoepithelioma of
      palate. CASE REPORT: A Hispanic female of 28 years old presented a not-ulcerate,
      painless ovoid swelling at left side of hard palate with a one year and a half of
      evolution. An excisional biopsy was done. The sample was fixed at 10% buffer
      formalin, embedded in paraffin, cuts at 5 micron and stained with H-E.
      Microscopically, the lesion was composed by myoepithelial neoplastic cells
      characterized by a round ovoid silhouette, an eccentric nuclei of dense chromatin
      and eosinophilic cytoplasm. In some myoepithelial neoplastic cells were
      identifies intranuclear cytoplasmatic inclusions. The lesion was analysed with
      immunohistochemical technique using the follow antibodies: vimentin, citokeratin
      AE1/AE3, S100 protein and actin muscle specific. We observe positive
      immunoreactivity against vimentin, citokeratin, S100 protein and actin muscle
      specific. A diagnosis of plasmacytoid myoephitelioma of palate salivary glands
      was done. Our findings supports the suggestion about plasmacytoid myoepithelioma
      is an independent entity. The histological diagnostic parameters of plasmacytoid
      myoepithelioma versus pleomorphic adenoma are discussed.

PMID- 18059238
TI  - Extramedullary hematopoiesis within endothelial papillary hyperplasia (Masson's
      pseudoangiosarcoma) of the tongue.
AB  - We report the unique association of Masson's pseudoangiosarcoma (endothelial
      papillary hyperplasia) and extramedullary hematopoiesis. The lesion was present
      as a violaceous nodule on the side of the tongue of a 78-year-old man with
      history of multiple myeloma and long-standing mild anemia. This association
      between a peculiar form of thrombus organization and extramedullary hematopoiesis
      has been reported previously only once, in an infant with a cranial hematoma, and
      raises interesting pathogenetic questions.

PMID- 18059239
TI  - Oral necrotizing microvasculitis in a patient affected by Kawasaki disease.
AB  - Kawasaki disease (KD) was first described in 1967 by Kawasaki, who defined it as
      "mucocutaneous lymph node syndrome". KD is an acute systemic vasculitis, which
      mainly involves medium calibre arteries; its origin is unknown, and it is
      observed in children under the age of 5, especially in their third year. The
      principal presentations of KD include fever, bilateral nonexudative
      conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities,
      rash, and cervical lymphadenopathy. Within KD, oral mucositis - represented by
      diffuse mucous membrane erythema, lip and tongue reddening and lingual papillae
      hypertrophy with subsequent development of strawberry tongue - can occur both in
      the acute stage of the disease (0-9 days), and in the convalescence stage (>25
      days) as a consequence of the pharmacological treatment. KD vascular lesions are
      defined as systemic vasculitis instead of systemic arteritis. This study analyzed
      the anatomical-pathological substrata of oral mucositis in a baby affected by
      Kawasaki disease and suddenly deceased for cardiac tamponade caused by coronary
      aneurysm rupture (sudden cardiac death of a mechanical type).

PMID- 18059240
TI  - Diagnostic evaluation of serial sections of labial salivary gland biopsies in
      Sjogren's syndrome.
AB  - OBJECTIVES: Sjogren's syndrome is a chronic inflammatory disease. The detection
      of chronic inflammatory infiltrates containing >50 lymphocytes (lymphocytic
      focus) per 4 mm2 tissue in minor salivary gland biopsies is a diagnostic
      parameter of the disease. The aim of the study was to examine if an increase in
      the tissue area of a single minor labial salivary gland biopsy through serial
      histological sections in patients affected by primary Sjogren's syndrome could
      facilitate the detection of the diagnostic focus score (grades >1 or >2).
      METHODS: We observed 24 labial salivary gland biopsies from patients affected by
      primary Sjogren's syndrome, diagnosed according to the clinical-laboratory
      criteria proposed by the American-European Consensus Group. The analysis was
      carried out on sections (n= 72) obtained at three different levels at 200
      micrometers from one another. The serial sections regarding the 3 levels were
      reviewed by the same oral pathologist, who detected both the total number of
      foci, and their surface, calculating a cumulative focus score. RESULTS: No
      significant correlation was found between the number of lobules per histological
      section and the focus score (Pearson correlation 0.363, p= 0.01). No significant
      variation in focus score distribution was identified in the three serial
      histological levels at 200 micrometers from one another. From the comparison
      between the number of lobules observed and the focus score grade, no direct
      proportionality between the amount of parenchyma analyzed and the focus score was
      found. CONCLUSIONS: The focus score remained unchanged in the serial sections at
      different depths.

PMID- 18059241
TI  - Program for coordinated dental care under general anaesthesia for children with
      special needs.
AB  - AIM: To draw up a program for coordination of dental care for children with
      special needs between the Course at the Universidad Complutense de Madrid (UCMC)
      (Specialisation in holistic dental care for children with special needs), and the
      Disabled Children's Oral Health Unit (DCOHU) within the Madrid Health Service
      (SERMAS). MATERIAL AND METHODS: UCMC Protocol for children with special needs.
      Design of a clinical pathway based on consensus amongst the professionals
      involved. RESULTS: Algorithm for dental care for children with special needs.
      Matrix covering all activities and timing for full dental diagnosis in such
      patients (general health, oral health and behaviour) to facilitate proper
      referral of patients requiring general anaesthesia. Inclusion in the matrix of
      those responsible for each activity. CONCLUSIONS: Improved team work (University 
      primary health care) in patient evaluation, in provision of information to
      parents and guardians and in health care quality. From the teaching point of
      view, students learn to adopt a systematic approach in the decision-making
      process.

PMID- 18059242
TI  - How to improve communication with deaf children in the dental clinic.
AB  - It may be difficult for hearing-impaired people to communicate with people who
      hear. In the health care area, there is often little awareness of the
      communication barriers faced by the deaf and, in dentistry, the attitude adopted
      towards the deaf is not always correct. A review is given of the basic rules and
      advice given for communicating with the hearing-impaired. The latter are
      classified in three groups - lip-readers, sign language users and those with
      hearing aids. The advice given varies for the different groups although the
      different methods of communication are often combined (e.g. sign language plus
      lip-reading, hearing-aids plus lip-reading). Treatment of hearing-impaired
      children in the dental clinic must be personalised. Each child is different,
      depending on the education received, the communication skills possessed, family
      factors (degree of parental protection, etc.), the existence of associated
      problems (learning difficulties), degree of loss of hearing, age, etc.

PMID- 18059243
TI  - New dental simulator for microsurgical training preliminary overview.
AB  - OBJECTIVE: To present a new simulator designed at the Minimally Invasive Surgery
      Centre (Caceres) which offers an integral, effective and viable training system
      that can be used for learning microsurgical techniques. STUDY DESIGN: A square
      methacrylate block was used. Animal jaws were fixed to the sides by means of
      butterfly screws. This block also has a drainage tube to facilitate the escape of
      fluids. RESULTS: Excellent results were obtained using this simulator in
      microsurgical suturing training in Dental, Oral and Maxillofacial Surgery.
      CONCLUSIONS: We believe that this simulator is an essential component in
      microsurgical training. It is an ethically and morally valid training method with
      which various suturing techniques can be practised before using live animals and
      before applying these to daily clinical practice.

PMID- 18059244
TI  - The post-endodontic periapical lesion: histologic and etiopathogenic aspects.
AB  - Apical periodontitis is produced in the majority of cases by intraradicular
      infection. Treatment consists in the elimination of the infectious agents by
      endodontia. Even when carrying out a correct cleansing and filling of canals, it
      is possible that periapical periodontitis will persist in the form of an
      asymptomatic radiolucency, giving rise to the post-endodontic periapical lesion.
      The chronic inflammatory periapical lesion is the most common pathology found in
      relation to alveolar bone of the jaw. From the histological point of view, it can
      be classified as chronic periapical periodontitis (periapical granuloma),
      radicular cyst, and as scar tissue. The most frequent is the periapical
      granuloma, constituted by a mass of chronic inflammatory tissue, in which
      isolated nests of epithelium can be found. The radicular cyst is characterized by
      the presence of a cavity, partially or wholly lined by epithelium. Scar tissue is
      a reparative response by the body, producing fibrous connective tissue. The aim
      of this study is to review and update the etiopathogenic and histological aspects
      of chronic post-endodontic periapical lesions.

PMID- 18059245
TI  - Drill failure during ORIF of the mandible. Complication management.
AB  - A case of a drill breakage during open reduction and internal fixation (ORIF) of
      a mandibular fracture is reported. The clinical decision, diagnosis and surgical
      management of the complication are described.

PMID- 18059246
TI  - Botryoid odontogenic cyst: clinical and pathological analysis in relation to
      recurrence.
AB  - OBJECTIVES: Botryoid odontogenic cyst (BOC) is considered as an unusual
      multilocular variant of lateral periodontal cyst (LPC). Review of the literature
      indicates that this lesion has higher risk of recurrence than LPC, but objective
      reasons are still unknown. The aim of this study is identify main clinical and
      pathological variables associated with the risk of recurrence. STUDY DESIGN: A
      complete literature review about cases of BOC was made, from its first
      description up to the year 2006. A total of 67 cases of BOC were identified from
      year 1973 (first case) to the last publication in 2005. RESULTS: 85.2% of the
      BOCs were located in the jaw, affecting to women (54.8% of the cases) in the
      fifth decade of the life. This lesion shows a well- circumscribed unilocular
      (60%) or multilocular (40%) radiolucency. Recurrence rate of cases with follow-up
      data was 32,4%. CONCLUSIONS: Size and multilocular patterns could be the main
      factors associated to recurrence in BOC.

PMID- 18059247
TI  - Spontaneous fracture of the mandibular genial tubercles. A case report.
AB  - Fracture of the mandibular genial tubercles is an uncommon pathology affecting
      edentulous patients with severe maxillary atrophy. Usually occurs spontaneously
      which complicates the diagnosis. Their importance lies in the functional
      alterations, which occur as a consequence of the disinsertion of the genihyoid
      and genioglossus muscles. The treatment of fracture of the genial tubercles is
      controversial, including no surgical intervention, excision of the avulsed bone
      fragments, and muscular repositioning. There have been only 11 cases reported in
      the literature of this fracture, most of them spontaneous. We present a difficult
      diagnosis situation of spontaneous fracture of the genial tubercles in an 86-year
      old edentulous female with a painful sublingual and submental hematoma and
      anterior cervical echimosis. Computerized Tomography should be made to confirm
      the diagnosis. Surgical treatment was not necessary, and follow-up at 6 months
      revealed complete symptomatic recovery, and full return of function.

PMID- 18059248
TI  - Progressive facial hemiatrophy with associated osseous lesions.
AB  - Progressive facial hemiatrophy (PFH) is a rare condition characterized by the
      slow, progressive appearance of a unilateral facial atrophy that affects the
      skin, subcutaneous tissue, muscle and bone. We report the case of a 60-year-old
      female patient whose cutaneous symptoms commenced in 1987 in the form of a
      purplish erythema on the left side of her face and neck, which subsequently
      remitted giving rise to an indurated region in the left maxillary region. Since
      1995 until the present day, she has developed facial hemiatrophy on the left side
      accompanied by progressive osseous reabsorption of the upper maxilla and left
      mandible with atrophy of soft tissue. The association of the onset of PFH with
      progressive osteolysis of the maxilla has not been previously reported in an
      adult patient.

PMID- 18059249
TI  - Third canal in the mesial root of permanent mandibular first molars: review of
      the literature and presentation of 3 clinical reports and 2 in vitro studies.
AB  - INTRODUCTION: Systematic anatomical studies corroborate the anatomical complexity
      of the root canal system. Deviations from the norm such as multiple orifices,
      apical deltas, accessory canals and other variations are frequent. OBJECTIVES: To
      present clinical reports of mandibular molars with three canals in the mesial
      root and two in vitro studies of the morphology of these canals, together with a
      review of the literature. MATERIALS AND METHODS: Three clinical reports are
      presented of mandibular molars where three canals in the mesial roots were
      treated endodontically. Two in vitro studies were performed, one using
      computerized tomography and the other with scanning electron microscopy, to
      describe the morphology of the mesial root canals of permanent first molars. The
      scientific literature on this anatomical situation was also reviewed. RESULTS:
      The tomographic study found that the prevalence of a third mesial canal in the 27
      teeth analysed was 14.81%; the microscopic study of 25 teeth found it to be 12%.
      The review of the literature encountered that the authors who report cases such
      as these found prevalences ranging from 1% to 15%. CONCLUSIONS: From the teeth
      analysed in vitro, it is concluded that a third mesial canal may be present in a
      mandibular first molar in approximately 13% of cases. Clinically, the third canal
      is difficult to find and exhibits a very variable morphology, which may present
      anastomosis with the other canals.

PMID- 18059250
TI  - Biomechanical aspects of external root resorption in orthodontic therapy.
AB  - External apical root resorption is a common phenomenon associated with
      orthodontic treatment. The factors relevant to root resorption can be divided
      into biological and mechanical factors. Some mechanical and biological factors
      might be associated with an increased or decreased risk of root resorption during
      orthodontic treatment. For mechanical factors, the extensive tooth movement, root
      torque and intrusive forces, movement type, orthodontic force magnitude, duration
      and type of force are involved. For biological factors, a genetic susceptibility,
      systemic disease, gender and medication intake have been demonstrated influence
      root resorption. Orthodontic therapy of patients with increased risk of root
      resorption should be carefully planned. Medical history, medication intake,
      family history, tooth agenesis, root morphology, oral health and habits must be
      considerate if we do not want jeopardize our patients by severe root resorption.
      To monitor apical root resorption the standard procedure is a radiographic
      examination after 6 months of treatment. In teeth with enhanced risk, a 3-month
      radiographic follow-up is recommended. The administration of anti-inflammatory
      drugs might suppress root resorption induced by orthodontic therapy, although
      none study was enough conclusive to indicate a protocol for patients with
      enhanced risk. In the event of multiple external root resorption, the diagnostic
      procedure should focus on the exclusion of the local factors and its associations
      (such as magnitude, duration and type of orthodontic force; periodontal disease;
      root form) that might lead to external root resorption. Systemic disorders
      associated with phosphorus-calcium metabolic alterations shall be suspected. This
      review searched the current knowledge of the mechanical and biological aspects of
      root resorption in orthodontic tooth movement.

PMID- 18059251
TI  - Oral health knowledge, attitudes and practice in 12-year-old schoolchildren.
AB  - OBJECTIVE: The objective of this study was to assess the association between
      knowledge, attitudes and practice of oral health in 12-year-old schoolchildren,
      and to analyse the findings in terms of the conventional KAP health-education
      model and of the critical approach. STUDY DESIGN: This study has a cross
      sectional design. The study participants were 1105 randomly selected 12-year-old
      children resident in the region of Galicia in Spain. For data collection, five
      teams of one dentist and one assistant were formed. The dentist carried out the
      physical examination and the assistant helped the subjects to answer the
      questionnaire. Knowledge, attitudes and practice were assessed, as well as oral
      health indicators. Multiple regression analysis was used to identify variables
      affecting practice (as measured by extent of plaque). RESULTS: The results of
      this study show how that there is an important association between oral health
      knowledge, attitudes, and practice in 12-year-old schoolchildren in this region.
      However, the results also show that attitude is not totally explained by
      knowledge, so that attitude cannot be understood simply as an intermediate
      variable in a knowledge practice causal chain. Specifically, the results indicate
      that sociocultural environment modifies the association knowledge, attitudes and
      practice. CONCLUSIONS: Within oral health education it is clearly important to
      increase public knowledge of the risk factors for dental disease. However, the
      efficacy of such education will be limited if health programs do not directly
      impinge on attitudes, and take into account factors related to the environment,
      education, social status and economic level of the targeted population.

PMID- 18059252
TI  - [Human diseases caused by chlamydia and chlamydophila].
AB  - Chlamydiae and Chlamydophilae are bacteria which are very common in the
      environment, the proof of which can be the recently described "environmental
      Chlamydiae". The classical Chlamydiae, such as Chlamydia trachomatis and
      Chlamydophila pneumoniae, posed a threat to human health, causing several
      diseases, including those with lethal course. In this article the biology and
      systematics of these bacteria and the diseases caused by them in humans,
      including those caused by classical and environmental Chlamydiae, are presented.

PMID- 18059253
TI  - Co-expression of the TGF-beta1 and TGF- beta2 isoforms in nasal polyps and in
      healthy mucosa.
AB  - BACKGROUND: The formation of nasal polyps is connected with a chronic
      inflammatory process with the activation of different cytokines. TGF-ss induces
      fibrosis and acts as a chemoattractant and proliferation factor for fibroblasts.
      The aim of the study was to evaluate the expression profiles of the genes coding
      TGF-ss isoforms in nasal polyps with predominately eosinophilic and neutrophilic
      infiltration and in healthy mucosa and to assess their mutual correlation with
      the levels of gene transcription. MATERIAL/METHODS: The study group consisted of
      24 patients with nasal polyposis. On the basis of the histopathological
      evaluation there were 16 eosinophilic and 8 neutrophilic polyps. The control
      group constituted 9 healthy patients. The expression profiles of the genes coding
      the TGF-ss isoforms were detected using real-time RT-QPCR. RESULTS: TGF-beta1 and
      TGF-beta2 mRNAs were revealed in 10 patients with eosinophilic polyps. TGF-beta1
      transcriptional activity was accompanied by TGF-beta2 transcriptional activity in
      nasal polyps. TGF-beta2 gene expression in tissues without mRNA for TGF-beta1 was
      silenced. There was positive correlation between the expressions of the TGF-beta1
      and TGF-beta2 isoforms in nasal polyps. TGF-beta1 mRNA was present at higher
      levels in all control samples than in eosinophilic polyps. An increased TGF-beta1
      mRNA expression was accompanied by an increased TGF-beta2 mRNA expression in
      healthy mucosa. TGF-beta3 showed the most intensive transcriptional activity
      among the TGF-ss isoforms in both nasal polyps and control tissues. There was no
      correlation between TGF-beta3 and TGF-beta1 nor between TGF-beta3 and TGF-beta2
      transcriptional activity in nasal polyps and normal tissue.

PMID- 18059254
TI  - A case of septic shock secondary to Corynebacterium aquaticum bacteremia
      occurring in an HIV-infected patient attending a promiscuous thermal SPA.
AB  - Corynebacterium aquaticum, an environmental organism associated with fresh water,
      has very seldom proved to be a cause of infection, although it has increasingly
      been isolated from clinical specimens. This report describes an unusual case of
      bacteremia occurring in an HIV-infected patient, complicated by septic shock and
      secondary to an epididimo-orchitis. Combination therapy of levofloxacin and
      metronidazole was used successfully.

PMID- 18059255
TI  - Colistin in combination with rifampin and imipenem for treating a blaVIM-1
      metallo-beta-lactamase-producing Enterobacter cloacae disseminated infection in a
      liver transplant patient.
AB  - A case of bla(VIM-1) producing E. cloacae disseminated infection in a patient
      submitted to orthotopic liver transplantation is described. Synergism between
      colistin, rifampin and imipenem was studied in vitro and this combination of
      three drugs was used to treat E. cloacae infection. The synergistic activity of
      this combination was demonstrated showing an increased activity of the serum
      bactericidal activity in comparison with the bactericidal activity of the serum
      taken during the previous therapy.

PMID- 18059256
TI  - Trends in childhood cancer mortality--United States, 1990-2004.
AB  - Cancer is the fourth most common cause of death (after unintentional injury,
      homicide, and suicide) among persons aged 1-19 years in the United States.
      Because recent childhood cancer mortality has not been well characterized in
      terms of temporal, demographic, and geographic trends, CDC analyzed cancer death
      rates among children (defined as aged 0-14 years) and adolescents (defined as
      aged 15-19 years) for the period 1990-2004 by sex, age group, race, ethnicity,
      U.S. Census region, and primary cancer site/leading diagnosis, using the most
      recent data available from the National Vital Statistics System (NVSS). This
      report describes the results of that analysis, which indicated that, overall, age
      adjusted childhood cancer death rates decreased significantly during 1990-2004
      among both sexes, both age groups, all races (except American Indians/Alaska
      Natives [AI/ANs]), Hispanics, non-Hispanics, and all U.S. Census regions.
      However, decreases in death rates varied among U.S. Census regions and between
      Hispanics and non-Hispanics. Eliminating racial/ethnic health disparities is one
      of the overarching goals of Healthy People 2010. Further research is needed to
      understand geographic and ethnic disparities in childhood cancer death rates.
      Moreover, cancer prevention and intervention measures should be designed to reach
      populations that are underserved and at high risk.

PMID- 18059257
TI  - Surveillance for travel-associated legionnaires disease--United States, 2005
      2006.
AB  - An estimated 8,000-18,000 persons are hospitalized with Legionnaires disease (LD)
      each year in the United States, and approximately 20% of reported LD cases are
      associated with travel. Outbreaks of travel-associated LD can be difficult to
      detect because travelers disperse and Legionella-specific diagnostic tests are
      underutilized. Consequently, clinicians and health departments often are unaware
      when more than one LD case is associated with a common travel destination. In
      2005, the Council of State and Territorial Epidemiologists (CSTE) adopted a
      position statement recommending enhanced surveillance measures for LD, with
      emphasis on diagnosis and reporting of confirmed travel-associated LD cases
      within 7 days. The rationale for enhanced surveillance was that earlier detection
      might lead to more rapid identification of a source (e.g., cooling tower) and
      expedite prevention measures (e.g., cleaning and chlorination). To 1) assess data
      from 32 states that used a supplementary reporting system for LD, 2) describe the
      epidemiology of travel-associated LD, and 3) compare characteristics of travel
      associated cases with those of cases not associated with travel, CDC analyzed LD
      cases reported via the supplementary system during 2005-2006. The results of that
      analysis indicated that the proportion of LD cases that were travel associated
      remained stable from 2005 (23%) to 2006 (25%), the proportion of travel
      associated cases reported via a dedicated CDC e-mail address increased from 11%
      to 24%, and the number of reported clusters of travel-associated LD increased
      from two in 2005 to eight in 2006. These results suggest that, to fully assess
      the benefits of enhanced LD surveillance, more states will need to adopt the CSTE
      recommendations.

PMID- 18059258
TI  - Brief report: respiratory syncytial virus activity--United States, July 2006
      November 2007.
AB  - Respiratory syncytial virus (RSV), the most common cause of severe lower
      respiratory tract disease among infants and young children, typically infects
      persons by age 2 years and can cause subsequent infections throughout life. RSV
      infection primarily manifests as bronchiolitis or pneumonia and results in
      approximately 75,000 to 125,000 hospitalizations in the United States each year.
      Persons at increased risk for severe disease or death include premature infants,
      older adults, and persons of any age with compromised respiratory, cardiac, or
      immune systems. RSV is transmitted from person to person via close contact,
      droplets, or fomites. In temperate climates, peak RSV activity typically occurs
      during the winter. However, year-to-year national and regional variability in the
      RSV season onset and offset occurs in the United States. RSV circulation also
      varies by geographic location; for example, Florida has an earlier season onset
      and a longer season than the rest of the United States. Using data reported to
      the National Respiratory and Enteric Virus Surveillance System (NREVSS), this
      report summarizes RSV temporal and geographic trends in the United States during
      the weeks ending July 8, 2006-June 30, 2007, and for the first 5 months of the
      current reporting season (the weeks ending July 7-November 24, 2007).
      Appropriately timed diagnostic tests can provide data that indicate when the RSV
      season begins nationally and regionally, information that has been critical in
      determining when to begin RSV prophylaxis for infants and children at high risk
      for infection.

PMID- 18059259
TI  - Generation of induced pluripotent stem cells without Myc from mouse and human
      fibroblasts.
AB  - Direct reprogramming of somatic cells provides an opportunity to generate patient
      or disease-specific pluripotent stem cells. Such induced pluripotent stem (iPS)
      cells were generated from mouse fibroblasts by retroviral transduction of four
      transcription factors: Oct3/4, Sox2, Klf4 and c-Myc. Mouse iPS cells are
      indistinguishable from embryonic stem (ES) cells in many respects and produce
      germline-competent chimeras. Reactivation of the c-Myc retrovirus, however,
      increases tumorigenicity in the chimeras and progeny mice, hindering clinical
      applications. Here we describe a modified protocol for the generation of iPS
      cells that does not require the Myc retrovirus. With this protocol, we obtained
      significantly fewer non-iPS background cells, and the iPS cells generated were
      consistently of high quality. Mice derived from Myc(-) iPS cells did not develop
      tumors during the study period. The protocol also enabled efficient isolation of
      iPS cells without drug selection. Furthermore, we generated human iPS cells from
      adult dermal fibroblasts without MYC.

PMID- 18059260
TI  - Redirecting lipoic acid ligase for cell surface protein labeling with small
      molecule probes.
AB  - Live cell imaging is a powerful method to study protein dynamics at the cell
      surface, but conventional imaging probes are bulky, or interfere with protein
      function, or dissociate from proteins after internalization. Here, we report
      technology for covalent, specific tagging of cellular proteins with chemical
      probes. Through rational design, we redirected a microbial lipoic acid ligase
      (LplA) to specifically attach an alkyl azide onto an engineered LplA acceptor
      peptide (LAP). The alkyl azide was then selectively derivatized with cyclo-octyne
      conjugates to various probes. We labeled LAP fusion proteins expressed in living
      mammalian cells with Cy3, Alexa Fluor 568 and biotin. We also combined LplA
      labeling with our previous biotin ligase labeling, to simultaneously image the
      dynamics of two different receptors, coexpressed in the same cell. Our
      methodology should provide general access to biochemical and imaging studies of
      cell surface proteins, using small fluorophores introduced via a short peptide
      tag.

PMID- 18059261
TI  - Discovery and characterization of a marine bacterial SAM-dependent chlorinase.
AB  - Halogen atom incorporation into a scaffold of bioactive compounds often amplifies
      biological activity, as is the case for the anticancer agent salinosporamide A
      (1), a chlorinated natural product from the marine bacterium Salinispora tropica.
      Significant effort in understanding enzymatic chlorination shows that oxidative
      routes predominate to form reactive electrophilic or radical chlorine species.
      Here we report the genetic, biochemical and structural characterization of the
      chlorinase SalL, which halogenates S-adenosyl-L-methionine (2) with chloride to
      generate 5'-chloro-5'-deoxyadenosine (3) and L-methionine (4) in a rarely
      observed nucleophilic substitution strategy analogous to that of Streptomyces
      cattleya fluorinase. Further metabolic tailoring produces a halogenated
      polyketide synthase substrate specific for salinosporamide A biosynthesis. SalL
      also accepts bromide and iodide as substrates, but not fluoride. High-resolution
      crystal structures of SalL and active site mutants complexed with substrates and
      products support the S(N)2 nucleophilic substitution mechanism and further
      illuminate halide specificity in this newly discovered halogenase family.

PMID- 18059262
TI  - An allosteric potentiator of M4 mAChR modulates hippocampal synaptic
      transmission.
AB  - Muscarinic acetylcholine receptors (mAChRs) provide viable targets for the
      treatment of multiple central nervous system disorders. We have used
      cheminformatics and medicinal chemistry to develop new, highly selective M4
      allosteric potentiators. VU10010, the lead compound, potentiates the M4 response
      to acetylcholine 47-fold while having no activity at other mAChR subtypes. This
      compound binds to an allosteric site on the receptor and increases affinity for
      acetylcholine and coupling to G proteins. Whole-cell patch clamp recordings
      revealed that selective potentiation of M4 with VU10010 increases carbachol
      induced depression of transmission at excitatory but not inhibitory synapses in
      the hippocampus. The effect was not mimicked by an inactive analog of VU10010 and
      was absent in M4 knockout mice. Selective regulation of excitatory transmission
      by M4 suggests that targeting of individual mAChR subtypes could be used to
      differentially regulate specific aspects of mAChR modulation of function in this
      important forebrain structure.

PMID- 18059263
TI  - Molecular basis of cyclin-CDK-CKI regulation by reversible binding of an inositol
      pyrophosphate.
AB  - When Saccharomyces cerevisiae cells are starved of inorganic phosphate, the Pho80
      Pho85 cyclin-cyclin-dependent kinase (CDK) is inactivated by the Pho81 CDK
      inhibitor (CKI). The regulation of Pho80-Pho85 is distinct from previously
      characterized mechanisms of CDK regulation: the Pho81 CKI is constitutively
      associated with Pho80-Pho85, and a small-molecule ligand, inositol
      heptakisphosphate (IP7), is required for kinase inactivation. We investigated the
      molecular basis of the IP7- and Pho81-dependent Pho80-Pho85 inactivation using
      electrophoretic mobility shift assays, enzyme kinetics and fluorescence
      spectroscopy. We found that IP7 interacts noncovalently with Pho80-Pho85-Pho81
      and induces additional interactions between Pho81 and Pho80-Pho85 that prevent
      substrates from accessing the kinase active site. Using synthetic peptides
      corresponding to Pho81, we define regions of Pho81 responsible for constitutive
      Pho80-Pho85 binding and IP7-regulated interaction and inhibition. These findings
      expand our understanding of the mechanisms of cyclin-CDK regulation and of the
      biochemical mechanisms of IP7 action.

PMID- 18059264
TI  - Neuromuscular consequences of reflexive covert orienting.
AB  - Visual stimulus presentation activates the oculomotor network without requiring a
      gaze shift. Here, we demonstrate that primate neck muscles are recruited during
      such reflexive covert orienting in a manner that parallels activity recorded from
      the superior colliculus (SC). Our results indicate the presence of a brainstem
      circuit whereby reflexive covert orienting is prevented from shifting gaze, but
      recruits neck muscles, predicting that similarities between SC and neck muscle
      activity should extend to other cognitive processes that are known to influence
      SC activity.

PMID- 18059265
TI  - Semaphorin-3A guides radial migration of cortical neurons during development.
AB  - Postmitotic neurons in the developing cortex migrate along radial glial fibers to
      their proper location in the cortical plate and form the layered structure. Here
      we report that the radial migration of rat layer II/III cortical neurons requires
      guidance by the extracellular diffusible factor Semaphorin-3A (Sema3A). This
      factor is expressed in a descending gradient across the cortical layers, whereas
      its receptor neuropilin-1 (NP1) is highly expressed in migrating neurons.
      Downregulation or conditional knockout of NP1 in newborn cortical neurons impedes
      their radial migration by disrupting their radial orientation during migration
      without altering their cell fate. Studies in cultured cortical slices further
      show that the endogenous gradient of Sema3A is required for the proper migration
      of newborn neurons. In addition, transwell chemotaxis assays show that isolated
      newborn neurons are attracted by Sema3A. Thus, Sema3A may function as a
      chemoattractive guidance signal for the radial migration of newborn cortical
      neurons toward upper layers.

PMID- 18059266
TI  - Psoriasis is associated with increased beta-defensin genomic copy number.
AB  - Psoriasis is a common inflammatory skin disease with a strong genetic component.
      We analyzed the genomic copy number polymorphism of the beta-defensin region on
      human chromosome 8 in 179 Dutch individuals with psoriasis and 272 controls and
      in 319 German individuals with psoriasis and 305 controls. Comparisons in both
      cohorts showed a significant association between higher genomic copy number for
      beta-defensin genes and risk of psoriasis.

PMID- 18059267
TI  - Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to
      systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multisystem complex autoimmune disease of
      uncertain etiology (OMIM 152700). Over recent years a genetic component to SLE
      susceptibility has been established. Recent successes with association studies in
      SLE have identified genes including IRF5 (refs. 4,5) and FCGR3B. Two tumor
      necrosis factor (TNF) superfamily members located within intervals showing
      genetic linkage with SLE are TNFSF4 (also known as OX40L; 1q25), which is
      expressed on activated antigen-presenting cells (APCs) and vascular endothelial
      cells, and also its unique receptor, TNFRSF4 (also known as OX40; 1p36), which is
      primarily expressed on activated CD4+ T cells. TNFSF4 produces a potent co
      stimulatory signal for activated CD4+ T cells after engagement of TNFRSF4 (ref.
      11). Using both a family-based and a case-control study design, we show that the
      upstream region of TNFSF4 contains a single risk haplotype for SLE, which is
      correlated with increased expression of both cell-surface TNFSF4 and the TNFSF4
      transcript. We hypothesize that increased expression of TNFSF4 predisposes to SLE
      either by quantitatively augmenting T cell-APC interaction or by influencing the
      functional consequences of T cell activation via TNFRSF4.

PMID- 18059268
TI  - Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated
      with chronic pancreatitis.
AB  - Chronic pancreatitis is a persistent inflammatory disease of the pancreas, in
      which the digestive protease trypsin has a fundamental pathogenetic role. Here we
      have analyzed the gene encoding the trypsin-degrading enzyme chymotrypsin C
      (CTRC) in German subjects with idiopathic or hereditary chronic pancreatitis. Two
      alterations in this gene, p.R254W and p.K247_R254del, were significantly
      overrepresented in the pancreatitis group, being present in 30 of 901 (3.3%)
      affected individuals but only 21 of 2,804 (0.7%) controls (odds ratio (OR) = 4.6;
      confidence interval (CI) = 2.6-8.0; P = 1.3 x 10(-7)). A replication study
      identified these two variants in 10 of 348 (2.9%) individuals with alcoholic
      chronic pancreatitis but only 3 of 432 (0.7%) subjects with alcoholic liver
      disease (OR = 4.2; CI = 1.2-15.5; P = 0.02). CTRC variants were also found in 10
      of 71 (14.1%) Indian subjects with tropical pancreatitis but only 1 of 84 (1.2%)
      healthy controls (OR = 13.6; CI = 1.7-109.2; P = 0.0028). Functional analysis of
      the CTRC variants showed impaired activity and/or reduced secretion. The results
      indicate that loss-of-function alterations in CTRC predispose to pancreatitis by
      diminishing its protective trypsin-degrading activity.

PMID- 18059271
TI  - CD19 is essential for B cell activation by promoting B cell receptor-antigen
      microcluster formation in response to membrane-bound ligand.
AB  - Here we describe the spatiotemporal architecture, at high molecular resolution,
      of receptors and signaling molecules during the early events of mouse B cell
      activation. In response to membrane-bound ligand stimulation, antigen aggregation
      occurs in B cell antigen receptor (BCR) microclusters containing immunoglobulin
      (Ig) M and IgD that recruit the kinase Syk and transiently associate with the
      coreceptor CD19. Unexpectedly, CD19-deficient B cells were significantly
      defective in initiation of BCR-dependent signaling, accumulation of downstream
      effectors and cell spreading, defects that culminated in reduced microcluster
      formation. Hence, we have defined the dynamics of assembly of the main
      constituents of the BCR 'signalosome' and revealed an essential role for CD19,
      independent of the costimulatory molecule CD21, in amplifying early B cell
      activation events in response to membrane-bound ligand stimulation.

PMID- 18059270
TI  - Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of
      store-operated calcium release-activated calcium channels.
AB  - CRACM1 (also called Orai1) constitutes the pore subunit of store-operated calcium
      release-activated calcium channels. A point mutation in the gene encoding CRACM1
      is associated with severe combined immunodeficiency disease in humans. Here we
      generated CRACM1-deficient mice in which beta-galactosidase activity 'reported'
      CRACM1 expression. CRACM1-deficient mice were smaller in size. Mast cells derived
      from CRACM1-deficient mice showed grossly defective degranulation and cytokine
      secretion, and the allergic reactions elicited in vivo were inhibited in CRACM1
      deficient mice. We detected robust CRACM1 expression in skeletal muscles and some
      regions of the brain, heart and kidney but not in the lymphoid regions of thymus
      and spleen. In contrast, we found CRACM2 expression to be much higher in mouse T
      cells. In agreement with those findings, the store-operated calcium influx and
      development and proliferation of CRACM1-deficient T cells was unaffected. Thus,
      CRACM1 is crucial in mouse mast cell effector function, but mouse T cell calcium
      release-activated calcium channels are functional in the absence of CRACM1.

PMID- 18059269
TI  - Germline rates of de novo meiotic deletions and duplications causing several
      genomic disorders.
AB  - Meiotic recombination between highly similar duplicated sequences (nonallelic
      homologous recombination, NAHR) generates deletions, duplications, inversions and
      translocations, and it is responsible for genetic diseases known as 'genomic
      disorders', most of which are caused by altered copy number of dosage-sensitive
      genes. NAHR hot spots have been identified within some duplicated sequences. We
      have developed sperm-based assays to measure the de novo rate of reciprocal
      deletions and duplications at four NAHR hot spots. We used these assays to
      dissect the relative rates of NAHR between different pairs of duplicated
      sequences. We show that (i) these NAHR hot spots are specific to meiosis, (ii)
      deletions are generated at a higher rate than their reciprocal duplications in
      the male germline and (iii) some of these genomic disorders are likely to have
      been underascertained clinically, most notably that resulting from the
      duplication of 7q11, the reciprocal of the deletion causing Williams-Beuren
      syndrome.

PMID- 18059272
TI  - Essential function for the calcium sensor STIM1 in mast cell activation and
      anaphylactic responses.
AB  - Mast cells have key functions as effectors of immunoglobulin E-mediated allergic
      inflammatory diseases. Allergen stimulation induces Ca2+ influx and elicits the
      secretion of inflammatory mediators from mast cells. Here we show that the Ca2+
      binding endoplasmic reticulum protein STIM1 is critical to mast cell function.
      STIM1-deficient fetal liver-derived mast cells had impaired Ca2+ influx mediated
      by the high-affinity immunoglobulin E receptor FcepsilonRI and activation of the
      transcription factors NF-kappaB and NFAT. Mast cells lacking STIM1 also had much
      less degranulation and cytokine production after FcepsilonRI stimulation. In
      addition, alterations in STIM1 expression affected the sensitivity of
      immunoglobulin E-mediated immediate-phase anaphylactic responses in vivo. Thus,
      STIM1 is key in promoting the Ca2+ influx that is essential for FcepsilonRI
      mediated mast cell activation and anaphylaxis.

PMID- 18059273
TI  - The contribution of transcription factor IRF1 to the interferon-gamma-interleukin
      12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells.
AB  - Interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) drive T helper type 1
      (T(H)1) differentiation, but the mechanisms underlying the regulation of the
      complicated gene networks involved in this differentiation are not fully
      understood. Here we show that the IFN-gamma-induced transcription factor IRF1 was
      essential in T(H)1 differentiation by acting on Il12rb1, the gene encoding the IL
      12 receptor beta1 subunit (IL-12Rbeta1). IRF1 directly interacted with and
      activated the Il12rb1 promoter in CD4+ T cells. Notably, the IRF1-dependent
      induction of IL-12Rbeta1 was essential for IFN-gamma-IL-12 signaling but was
      dispensable for IL-23-IL-17 signaling. Because both IL-12 and IL-23 bind to and
      transmit signals through IL-12Rbeta1, our data suggest that distinct thresholds
      of IL-12Rbeta1 expression are required for T(H)1 versus T(H)-17 differentiation.

PMID- 18059274
TI  - Gate-induced insulating state in bilayer graphene devices.
AB  - The potential of graphene-based materials consisting of one or a few layers of
      graphite for integrated electronics originates from the large room-temperature
      carrier mobility in these systems (approximately 10,000 cm2 V(-1) s(-1)).
      However, the realization of electronic devices such as field-effect transistors
      will require controlling and even switching off the electrical conductivity by
      means of gate electrodes, which is made difficult by the absence of a bandgap in
      the intrinsic material. Here, we demonstrate the controlled induction of an
      insulating state--with large suppression of the conductivity--in bilayer
      graphene, by using a double-gate device configuration that enables an electric
      field to be applied perpendicular to the plane. The dependence of the resistance
      on temperature and electric field, and the absence of any effect in a single
      layer device, strongly suggest that the gate-induced insulating state originates
      from the recently predicted opening of a bandgap between valence and conduction
      bands.

PMID- 18059275
TI  - Three-dimensional photonic metamaterials at optical frequencies.
AB  - Metamaterials are artificially structured media with unit cells much smaller than
      the wavelength of light. They have proved to possess novel electromagnetic
      properties, such as negative magnetic permeability and negative refractive index.
      This enables applications such as negative refraction, superlensing and
      invisibility cloaking. Although the physical properties can already be
      demonstrated in two-dimensional (2D) metamaterials, the practical applications
      require 3D bulk-like structures. This prerequisite has been achieved in the
      gigahertz range for microwave applications owing to the ease of fabrication by
      simply stacking printed circuit boards. In the optical domain, such an elegant
      method has been the missing building block towards the realization of 3D
      metamaterials. Here, we present a general method to manufacture 3D optical
      (infrared) metamaterials using a layer-by-layer technique. Specifically, we
      introduce a fabrication process involving planarization, lateral alignment and
      stacking. We demonstrate stacked metamaterials, investigate the interaction
      between adjacent stacked layers and analyse the optical properties of stacked
      metamaterials with respect to an increasing number of layers.

PMID- 18059276
TI  - Sliding charge-density wave in manganites.
AB  - Stripe and chequerboard phases appear in many metal oxide compounds, and are
      thought to be linked to exotic behaviour such as high-temperature
      superconductivity and colossal magnetoresistance. It is therefore extremely
      important to understand the fundamental nature of such phases. The so-called
      stripe phase of the manganites has long been interpreted as the localization of
      charge at atomic sites. Here, we present resistance measurements on
      La(0.50)Ca(0.50)MnO(3) that strongly suggest that this state is in fact a
      prototypical charge-density wave (CDW) that undergoes collective transport.
      Dramatic resistance hysteresis effects and broadband noise properties are
      observed, both of which are typical of sliding CDW systems. Moreover, the high
      levels of disorder typical of manganites result in behaviour similar to that of
      well-known disordered CDW materials. The CDW-type behaviour of the manganite
      superstructure suggests that unusual transport and structural properties do not
      require exotic physics, but could emerge when a well-understood phase (the CDW)
      coexists with disorder.

PMID- 18059277
TI  - Thermochromism in an organic crystal based on the coexistence of sigma- and pi
      dimers.
AB  - Transition-metal complexes and organic radical molecules can be used to make
      electric conductors and ferromagnets, the optical properties of which can be
      controlled by changing temperature and are used as molecular switches and
      sensors. Whereas a number of organic radicals in solution show temperature
      dependent optical properties, such behaviour in crystalline forms is more rare.
      Here, we show a fully reversible continuous thermochromism with a unique
      mechanism in purely organic crystals of diazaphenalenyl radical. This behaviour
      is based on changes in the diazaphenalenyl dimers coexisting in the crystal. From
      the X-ray crystal structure analyses and temperature-dependent visible spectra,
      we conclude the presence of a thermal equilibrium between sigma-bonded and pi
      bonded dimers, which are separated by 2.62(6) kcal mol(-1). This conclusion is
      supported by room-temperature electron spin resonance spectra of the solid, which
      showed signals that are attributable to a thermally accessible triplet state of
      the pi-dimer structure. This proves the coexistence of two dimers of different
      bonding natures in the crystal, causing it to demonstrate thermometer-like
      behaviour.

PMID- 18059278
TI  - Resolution of de novo HIV production and trafficking in immature dendritic cells.
AB  - The challenge in observing de novo virus production in human immunodeficiency
      virus (HIV)-infected dendritic cells (DCs) is the lack of resolution between
      cytosolic immature and endocytic mature HIV gag protein. To track HIV production,
      we developed an infectious HIV construct bearing a diothiol-resistant
      tetracysteine motif (dTCM) at the C terminus of HIV p17 matrix within the HIV gag
      protein. Using this construct in combination with biarsenical dyes, we observed
      restricted staining of the dTCM to de novo-synthesized uncleaved gag in the DC
      cytosol. Co-staining with HIV gag antibodies, reactive to either p17 matrix or
      p24 capsid, preferentially stained mature virions and thus allowed us to track
      the virus at distinct stages of its life cycle within DCs and upon transfer to
      neighboring DCs or T cells. Thus, in staining HIV gag with biarsenical dye system
      in situ, we characterized a replication-competent virus capable of being tracked
      preferentially within infected leukocytes and observed in detail the dynamic
      nature of the HIV production and transfer in primary DCs.

PMID- 18059279
TI  - Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis
      lung disease.
AB  - Interleukin-8 (IL-8) activates neutrophils via the chemokine receptors CXCR1 and
      CXCR2. However, the airways of individuals with cystic fibrosis are frequently
      colonized by bacterial pathogens, despite the presence of large numbers of
      neutrophils and IL-8. Here we show that IL-8 promotes bacterial killing by
      neutrophils through CXCR1 but not CXCR2. Unopposed proteolytic activity in the
      airways of individuals with cystic fibrosis cleaved CXCR1 on neutrophils and
      disabled their bacterial-killing capacity. These effects were protease
      concentration-dependent and also occurred to a lesser extent in individuals with
      chronic obstructive pulmonary disease. Receptor cleavage induced the release of
      glycosylated CXCR1 fragments that were capable of stimulating IL-8 production in
      bronchial epithelial cells via Toll-like receptor 2. In vivo inhibition of
      proteases by inhalation of alpha1-antitrypsin restored CXCR1 expression and
      improved bacterial killing in individuals with cystic fibrosis. The cleavage of
      CXCR1, the functional consequences of its cleavage, and the identification of
      soluble CXCR1 fragments that behave as bioactive components represent a new
      pathophysiologic mechanism in cystic fibrosis and other chronic lung diseases.

PMID- 18059280
TI  - Therapeutic differentiation and maturation of lymphatic vessels after lymph node
      dissection and transplantation.
AB  - Surgery or radiation therapy of metastatic cancer often damages lymph nodes,
      leading to secondary lymphedema. Here we show, using a newly established mouse
      model, that collecting lymphatic vessels can be regenerated and fused to lymph
      node transplants after lymph node removal. Treatment of lymph node-excised mice
      with adenovirally delivered vascular endothelial growth factor-C (VEGF-C) or VEGF
      D induced robust growth of the lymphatic capillaries, which gradually underwent
      intrinsic remodeling, differentiation and maturation into functional collecting
      lymphatic vessels, including the formation of uniform endothelial cell-cell
      junctions and intraluminal valves. The vessels also reacquired pericyte contacts,
      which downregulated lymphatic capillary markers during vessel maturation. Growth
      factor therapy improved the outcome of lymph node transplantation, including
      functional reconstitution of the immunological barrier against tumor metastasis.
      These results show that growth factor-induced maturation of lymphatic vessels is
      possible in adult mice and provide a basis for future therapy of lymphedema.

PMID- 18059281
TI  - In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as
      essential for the bacteria to persist in mice.
AB  - The success of Mycobacterium tuberculosis (Mtb) as a human pathogen relies on its
      ability to resist eradication by the immune system. The identification of
      mechanisms that enable Mtb to persist is key for finding ways to limit latent
      tuberculosis, which affects one-third of the world's population. Here we show
      that conditional gene silencing can be used to determine whether an Mtb gene
      required for optimal growth in vitro is also important for virulence and, if so,
      during which phase of an infection it is required. Application of this approach
      to the prcBA genes, which encode the core of the mycobacterial proteasome,
      revealed an unpredicted requirement of the core proteasome for the persistence of
      Mtb during the chronic phase of infection in mice. Proteasome depletion also
      attenuated Mtb in interferon-gamma-deficient mice, pointing to a function of the
      proteasome beyond defense against the adaptive immune response. Genes that are
      essential for growth in vitro, in vivo or both account for approximately 20% of
      Mtb's genome. Conditional gene silencing could therefore facilitate the
      validation of up to 800 potential Mtb drug targets and improve our understanding
      of host-pathogen dynamics.

PMID- 18059282
TI  - PPAR-gamma regulates osteoclastogenesis in mice.
AB  - Osteoclasts are bone-resorbing cells derived from hematopoietic precursors of the
      monocyte-macrophage lineage. Regulation of osteoclast function is central to the
      understanding of bone diseases such as osteoporosis, rheumatoid arthritis and
      osteopetrosis. Although peroxisome proliferator-activated receptor-gamma (PPAR
      gamma) has been shown to inhibit osteoblast differentiation, its role, if any, in
      osteoclasts is unknown. This is a clinically crucial question because PPAR-gamma
      agonists, "such as thiazolidinediones-" a class of insulin-sensitizing drugs,
      have been reported to cause a higher rate of fractures in human patients. Here we
      have uncovered a pro-osteoclastogenic effect of PPAR-gamma by using a
      Tie2Cre/flox mouse model in which PPAR-gamma is deleted in osteoclasts but not in
      osteoblasts. These mice develop osteopetrosis characterized by increased bone
      mass, reduced medullary cavity space and extramedullary hematopoiesis in the
      spleen. These defects are the result of impaired osteoclast differentiation and
      compromised receptor activator of nuclear factor-kappaB ligand signaling and can
      be rescued by bone marrow transplantation. Moreover, ligand activation of PPAR
      gamma by rosiglitazone exacerbates osteoclast differentiation in a receptor
      dependent manner. Our examination of the underlying mechanisms suggested that
      PPAR-gamma functions as a direct regulator of c-fos expression, an essential
      mediator of osteoclastogenesis. Therefore, PPAR-gamma and its ligands have a
      previously unrecognized role in promoting osteoclast differentiation and bone
      resorption.

PMID- 18059283
TI  - Antidepressant actions of the exercise-regulated gene VGF.
AB  - Exercise has many health benefits, including antidepressant actions in depressed
      human subjects, but the mechanisms underlying these effects have not been
      elucidated. We used a custom microarray to identify a previously undescribed
      profile of exercise-regulated genes in the mouse hippocampus, a brain region
      implicated in mood and antidepressant response. Pathway analysis of the regulated
      genes shows that exercise upregulates a neurotrophic factor signaling cascade
      that has been implicated in the actions of antidepressants. One of the most
      highly regulated target genes of exercise and of the growth factor pathway is the
      gene encoding the VGF nerve growth factor, a peptide precursor previously shown
      to influence synaptic plasticity and metabolism. We show that administration of a
      synthetic VGF-derived peptide produces a robust antidepressant response in mice
      and, conversely, that mutation of VGF in mice produces the opposite effects. The
      results suggest a new role for VGF and identify VGF signaling as a potential
      therapeutic target for antidepressant drug development.

PMID- 18059284
TI  - Evidence of fibril-like beta-sheet structures in a neurotoxic amyloid
      intermediate of Alzheimer's beta-amyloid.
AB  - Diffusible subfibrillar aggregates of amyloid proteins are potent neurotoxins and
      primary suspects in amyloid diseases including Alzheimer's disease. Despite
      widespread interest, the molecular structures of the amyloid intermediates and
      the conformational conversions in amyloid misfolding are poorly understood. Here
      we present a molecular-level examination of sequence-specific secondary
      structures and supramolecular structures of a neurotoxic amyloid intermediate of
      the 40-residue beta-amyloid (Abeta) peptide involved in Alzheimer's disease.
      Using solid-state NMR and electron microscopy, we show that, before
      fibrillization, natively unstructured monomeric Abeta is subject to large
      conformational changes into a spherical amyloid intermediate of 15-35 nm
      diameter, which has predominantly parallel beta-sheet structures. Structural
      comparison with Abeta fibrils demonstrates that formation of this beta-sheet
      intermediate I(beta) largely defines conformational transitions in amyloid
      misfolding. Neurotoxicity assays on PC12 cells show that I(beta) shows higher
      toxicity than the fibril, indicating that the beta-sheet formation may trigger
      neurotoxicity.

PMID- 18059286
TI  - Substrate RNA positioning in the archaeal H/ACA ribonucleoprotein complex.
AB  - The most complex RNA pseudouridylases are H/ACA ribonucleoprotein particles,
      which use a guide RNA for substrate capture and four proteins (Cbf5, Nop10, Gar1
      and L7Ae/NHP2) for substrate modification. Here we report the three-dimensional
      structure of a catalytically deficient archaeal enzyme complex (including the
      guide RNA and three of the four essential proteins) bound to a substrate RNA.
      Extensive interactions of Cbf5 with one guide-substrate helix and a guide RNA
      stem shape the forked guide-substrate RNA complex structure and position the
      substrate in proximity of the Cbf5 catalytic center. Our structural and
      complementary fluorescence analyses also indicate that precise placement of the
      target uridine at the active site requires a conformation of the guide-substrate
      RNA duplex that is brought about by the previously identified concurrent
      interaction of the guide RNA with L7Ae and a composite Cbf5-Nop10 surface, and
      further identify a residue that is critical in this process.

PMID- 18059287
TI  - Structure of phage P22 cell envelope-penetrating needle.
AB  - Bacteriophage P22 infects Salmonella enterica by injecting its genetic material
      through the cell envelope. During infection, a specialized tail needle, gp26, is
      injected into the host, likely piercing a hole in the host cell envelope. The 2.1
      A crystal structure of gp26 reveals a 240-A elongated protein fiber formed by two
      trimeric coiled-coil domains interrupted by a triple beta-helix.The N terminus of
      gp26 plugs the portal protein channel, retaining the genetic material inside the
      virion. The C-terminal tip of the fiber exposes beta-hairpins with hydrophobic
      tips similar to those seen in class II fusion peptides. The alpha-helical core
      connecting these two functionally polarized tips presents four trimerization
      octads with consensus sequence IXXLXXXV. The slender conformation of the gp26
      fiber minimizes the surface exposed to solvent, which is consistent with the idea
      that gp26 traverses the cell envelope lipid bilayers.

PMID- 18059288
TI  - The versatility of Shigella effectors.
AB  - When Shigella infect the intestinal epithelium, they deliver several effectors
      through the type III secretion system (T3SS) into the surrounding space and
      directly into the host-cell cytoplasm, where they can mimic and usurp host
      cellular functions or subvert host-cell signalling pathways and the immune
      response. Although bacterial strategies and mechanisms of infection vary greatly,
      recent studies of Shigella effectors have revealed that Shigella possess a highly
      evolved strategy for infection.

PMID- 18059289
TI  - Kiss and spit: the dual roles of Toxoplasma rhoptries.
AB  - Toxoplasma gondii is a single-celled, eukaryotic parasite that can only reproduce
      inside a host cell. Upon entry, this Apicomplexan parasite co-opts host functions
      for its own purposes. An unusual set of apical organelles, named rhoptries,
      contain some of the machinery that is used by T. gondii both for invasion and to
      commandeer host functions. Of particular interest are a group of injected protein
      kinases that are among the most variable of all the T. gondii proteins. At least
      one of these kinases has a major effect on host-gene expression, including the
      modulation of key regulators of the immune response. Here, we discuss these
      recent findings and use them to propose a model in which an expansion of host
      range is a major force that drives rhoptry-protein evolution.

PMID- 18059290
TI  - Getting organized--how bacterial cells move proteins and DNA.
AB  - In recent years, the subcellular organization of prokaryotic cells has become a
      focal point of interest in microbiology. Bacteria have evolved several different
      mechanisms to target protein complexes, membrane vesicles and DNA to specific
      positions within the cell. This versatility allows bacteria to establish the
      complex temporal and spatial regulatory networks that couple morphological and
      physiological differentiation with cell-cycle progression. In addition to
      stationary localization factors, dynamic cytoskeletal structures also have a
      fundamental role in many of these processes. In this Review, we summarize the
      current knowledge on localization mechanisms in bacteria, with an emphasis on the
      role of polymeric protein assemblies in the directed movement and positioning of
      macromolecular complexes.

PMID- 18059292
TI  - Boosting competition?

PMID- 18059294
TI  - Colloids: a useful boundary.

PMID- 18059295
TI  - Semiconductors: a new class of metamaterials.

PMID- 18059296
TI  - Supramolecular assembly: nanofibre whirlpools.

PMID- 18059297
TI  - Quasicrystals: comparative dynamics.

PMID- 18059298
TI  - Material witness: golden wonder.

PMID- 18059299
TI  - Transition metal oxides: the exciting world of orbitals.

PMID- 18059300
TI  - Hope, hype and hypocrisy.

PMID- 18059301
TI  - Comment on the multi-person interview: "the future of research universities".

PMID- 18059302
TI  - Drp1 phosphorylation and mitochondrial regulation.

PMID- 18059305
TI  - Public health and civil liberties. Introduction to the talking point on public
      health versus civil liberties.

PMID- 18059306
TI  - Your liberty or your life. Talking Point on public health versus civil liberties.

PMID- 18059307
TI  - The continuing tensions between individual rights and public health. Talking
      Point on public health versus civil liberties.

PMID- 18059308
TI  - The impact of CO2. The global rise in the levels of CO2 is good for trees, bad
      for grasses and terrible for corals.

PMID- 18059309
TI  - Taking on creationism. Which arguments and evidence counter pseudoscience?

PMID- 18059310
TI  - On the relationship of LDL and VEGFR1: not just a family affair.

PMID- 18059311
TI  - A variable topology for the 30-nm chromatin fibre.
AB  - The structure of the 30-nm chromatin fibre is an important determinant of the
      regulation of eukaryotic transcription. A fundamental issue is whether the
      stacking of nucleosomes in this fibre is organized as a one-start or two-start
      helix. We argue that all recent experimental data are compatible with a two-start
      helix and propose that the topology of the fibre, but not the mode of stacking
      the nucleosomes, is dependent on the length of the linker DNA. This arrangement
      conserves nucleosome stacking and thus the external morphology of the fibre, and
      also ensures that the fibre adopts the highest available packing density.

PMID- 18059312
TI  - Towards completion of the Earth's proteome.
AB  - New protein sequences are deposited in databases at an accelerating pace;
      however, many of these are homologous to known proteins and could be considered
      redundant. If all historical releases of the protein database are analysed using
      the original sequence-clustering procedure described here, the fraction of newly
      sequenced proteins that are redundant is increasing. We interpret this as an
      indication that the sequencing of the Earth's proteome--the complete set of
      proteins on Earth--is approaching completion. We estimate the approximate size of
      the Earth's proteome to be 5 million sequences, most of which will be identified
      during the next 5 years. As the Earth's proteome nears completion, cluster
      analysis of the protein database will become essential to identify under-explored
      taxa to which future sequencing efforts should be directed and to focus research
      on protein families without experimental characterization.

PMID- 18059314
TI  - Drugs and trafficking of ion channels: a new pro-arrhythmic threat on the
      horizon?
AB  - Tuning of functional expression levels of the ion channels that make up the
      cardiac action potential (AP) is crucial for preserving correct AP duration (APD)
      and QTc times. Many compounds inhibit human ether-a-go-go related gene (hERG)
      mediated delayed rectifier currents and thus prolong cardiac repolarization that
      may cause life-threatening arrhythmias like Torsades de Pointes. An increasing
      number of drugs are found to inhibit hERG function by a dual mechanism of short
      term channel block and long-term trafficking defects that operate over different
      time and concentration scales. In safety screens at present used by
      pharmaceutical companies, the short-term effect of channel block is covered. In
      contrast, specific screening for long-term trafficking defects is not common,
      with the consequent risk of drugs that disturb trafficking entering the market.
      Whether that poses another pro-arrhythmic threat for the patients treated has to
      be determined, but is not unlikely.

PMID- 18059313
TI  - Interleukin 2: from immunostimulation to immunoregulation and back again.
AB  - Interleukin 2 (IL-2) was one of the first cytokines to be discovered. However,
      the complex role of IL-2 and its receptor in the regulation of immune responses
      is only now emerging. This review explores the various signals triggered by IL-2
      and discusses their translation into biological function. A model is outlined
      that accommodates the seemingly contradictory functions of IL-2, and explains how
      one cytokine can be an essential T-cell growth and differentiation factor and yet
      also be indispensable to maintain peripheral tolerance.

PMID- 18059315
TI  - Probing the role of AMPAR endocytosis and long-term depression in behavioural
      sensitization: relevance to treatment of brain disorders, including drug
      addiction.
AB  - Modifying the function of postsynaptic alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid subtype glutamate receptors (AMPARs) is one of the most important
      mechanisms by which the efficacy of synaptic transmission at excitatory
      glutamatergic synapses in the mammalian brain is regulated. Traditionally these
      types of modifications have been thought to be achieved mainly by altering the
      channel gating properties or conductance of the receptors. A large body of
      evidence accumulated from recent studies strongly suggests that AMPARs, like most
      integral plasma membrane proteins, are continuously recycled between the plasma
      membrane and the intracellular compartments via vesicle-mediated plasma membrane
      insertion and clathrin-dependent endocytosis. Regulation of either receptor
      insertion or endocytosis results in a rapid change in the number of these
      receptors expressed on the plasma membrane surface and in the receptor-mediated
      responses, thereby playing an important role in mediating certain forms of
      synaptic plasticity, such as long-term potentiation (LTP) and depression (LTD).
      These studies have significantly advanced our understanding of the molecular
      mechanisms underlying LTP and LTD, and their potential contributions to learning
      and memory-related behaviours. Here I provide a brief summary of the current
      state of knowledge concerning clathrin-mediated AMPAR endocytosis and its
      relationship to the expression of certain forms of LTD in several brain areas.
      The potential impact of recent advancements on our efforts to probe the roles of
      synaptic plasticity in learning and memory-related behaviours, and their
      relevance to some brain disorders, particularly drug addiction, are also
      discussed.

PMID- 18059316
TI  - Conformational changes in G-protein-coupled receptors-the quest for functionally
      selective conformations is open.
AB  - The G-protein-coupled receptors (GPCRs) represent one the largest families of
      drug targets. Upon agonist binding a receptor undergoes conformational
      rearrangements that lead to a novel protein conformation which in turn can
      interact with effector proteins. During the last decade significant progress has
      been made to prove that different conformational changes occur. Today it is
      mostly accepted that individual ligands can induce different receptor
      conformations. However, the nature or molecular identity of the different
      conformations is still ill-known. Knowledge of the potential functionally
      selective conformations will help to develop drugs that select specific
      conformations of a given GPCR which couple to specific signalling pathways and
      may, ultimately, lead to reduced side effects. In this review we will summarize
      recent progress in biophysical approaches that have led to the current
      understanding of conformational changes that occur during GPCR activation.

PMID- 18059317
TI  - Region-specific effects of N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide on
      nicotine-induced increase in extracellular dopamine in vivo.
AB  - BACKGROUND AND PURPOSE: Systemic administration of N,N'-dodecane-1,12-diyl-bis-3
      picolinium dibromide (bPiDDB), an antagonist of nicotinic acetylcholine receptors
      (nAChRs) attenuated the nicotine-induced increase in dopamine levels in nucleus
      accumbens (NAcc). EXPERIMENTAL APPROACH: Using in vivo microdialysis, we
      investigated the effects of local perfusion of the novel nAChR antagonist bPiDDB
      into the NAcc or ventral tegmental area (VTA) on increased extracellular dopamine
      in NAcc, induced by systemic nicotine. We also examined the concentration
      dependent effects of bPiDDB on the acetylcholine (ACh)-evoked response of
      specific recombinant neuronal nAChR subtypes expressed in Xenopus oocytes, using
      electrophysiological methods. KEY RESULTS: Nicotine (0.4 mg kg(-1), s.c.)
      increased extracellular dopamine in NAcc, which was attenuated by intra-VTA
      perfusion of mecamylamine (100 microM). Intra-VTA perfusion of bPiDDB (1 and 10
      microM) reduced nicotine-induced increases in extracellular dopamine in NAcc. In
      contrast, intra-NAcc perfusion of bPiDDB (1 or 10 microM) failed to alter the
      nicotine-induced increase in dopamine in NAcc. Intra-VTA perfusion of bPiDDB
      alone did not alter basal dopamine levels, compared to control, nor the increased
      dopamine in NAcc following amphetamine (0.5 mg kg(-1), s.c.). Using Xenopus
      oocytes, bPiDDB (0.01-100 microM) inhibited the response to ACh on specific
      combinations of rat neuronal nAChR subunits, with highest potency at
      alpha3beta4beta3 and lowest potency at alpha6/3beta2beta3. CONCLUSIONS AND
      IMPLICATIONS: bPiDDB-Sensitive nAChRs involved in regulating nicotine-induced
      dopamine release are located in the VTA, rather than in the NAcc. As bPiDDB has
      properties different from the prototypical nAChR antagonist mecamylamine, further
      development may lead to novel nAChR antagonists for the treatment of tobacco
      dependence.

PMID- 18059318
TI  - Interleukin-1-induced interleukin-6 synthesis is mediated by the neutral
      sphingomyelinase/Src kinase pathway in neurones.
AB  - BACKGROUND AND PURPOSE: Interleukin (IL)-1 is a key mediator of inflammatory and
      host defence responses and its effects in the brain are mediated primarily via
      effects on glia. IL-1 induces release of inflammatory mediators such as IL-6 from
      glia via the type-1 receptor (IL-1R1) and established signalling mechanisms
      including mitogen-activated protein kinases and nuclear factor kappa-B. IL-1 also
      modifies physiological functions via actions on neurones, through activation of
      the neutral sphingomyelinase (nSMase)/Src kinase signalling pathway, although the
      mechanism of IL-1-induced IL-6 synthesis in neurones remains unknown.
      EXPERIMENTAL APPROACH: Primary mouse neuronal cell cultures, ELISA, Western blot
      and immunocytochemistry techniques were used. KEY RESULTS: We show here that IL
      1beta induces the synthesis of IL-6 in primary mouse neuronal cultures, and this
      is dependent on the activation of IL-1R1, nSMase and Src kinase. We demonstrate
      that IL-1beta-induced Src kinase activation triggers the phosphorylation of the
      NMDA receptor NR2B subunit, leading to activation of Ca(2+)/calmodulin-dependent
      protein kinase II (CamKII) and the nuclear transcription factor CREB. We also
      show that NR2B, CamKII and CREB are essential signalling elements involved in IL
      1beta-induced IL-6 synthesis in neurones. CONCLUSIONS AND IMPLICATIONS: These
      results demonstrate that IL-1 interacts with the same receptors on neurones and
      glia to elicit IL-6 release, but does so via distinct signalling pathways. The
      mechanism by which IL-1beta induces IL-6 synthesis in neurones could be critical
      in both physiological and pathophysiological actions of IL-1beta, and may provide
      a new therapeutic target for the treatment of acute CNS injury.

PMID- 18059319
TI  - Oxytocin stimulates migration and invasion in human endothelial cells.
AB  - BACKGROUND AND PURPOSE: It has recently been reported that oxytocin is produced
      by some tumour cell types, and that oxytocin receptors, belonging to the G
      protein-coupled receptor (GPCR) family, are expressed in a variety of cell types.
      Among these, human umbilical vein endothelial cells (HUVECs) respond to oxytocin
      with an increased proliferation, suggesting a possible role for the hormone in
      the regulation of angiogenesis. EXPERIMENTAL APPROACH: We employed chemotaxis and
      chemoinvasion assays to characterize the effect of oxytocin on HUVEC motility,
      and immunoblot analysis to study its molecular mechanisms of action. KEY RESULTS:
      We showed that oxytocin stimulates migration and invasion in HUVECs via oxytocin
      receptor activation. Searching for the molecular mechanism(s) responsible for
      oxytocin's pro-migratory effect, we identified the Gq coupling of oxytocin
      receptors and phospholipase C (PLC) as the main effectors of oxytocin's action in
      HUVECs. We also found that oxytocin stimulates the phosphorylation of endothelial
      nitric oxide synthase (eNOS) via the phosphatidylinositol-3-kinase (PI-3-K)/AKT
      pathway, and that the activation of PI-3-K and formation of nitric oxide (NO) are
      required for the pro-migratory effect of oxytocin. CONCLUSIONS AND IMPLICATIONS:
      The ability of oxytocin to stimulate HUVEC motility and invasion suggests that
      the hormone can participate in physiopathological processes where activation of
      endothelial cells plays an important role, for example, in angiogenesis.
      Interestingly, both the AKT and eNOS phosphorylation induced by oxytocin receptor
      activation depended on PLC activity, thus suggesting the existence of a still
      undefined mechanism connecting PLC to the PI-3-K/AKT pathway, upon oxytocin
      stimulation.

PMID- 18059320
TI  - Inhibitors of histone deacetylase (HDAC) restore the p53 pathway in neuroblastoma
      cells.
AB  - BACKGROUND AND PURPOSE: Inhibitors of histone deacetylase (HDAC) are emerging as
      a promising class of anti-cancer drugs, but a generic deregulation of
      transcription in neoplastic cells cannot fully explain their therapeutic effects.
      In this study we evaluated alternative molecular mechanisms by which HDAC
      inhibitors could affect neuroblastoma viability. EXPERIMENTAL APPROACH: Effects
      of HDAC inhibitors on survival of the I-type SK-N-BE and the N-type NB SH-SY5Y
      neuroblastoma cell lines were assessed by the MTT assay. Molecular pathways
      leading to this were examined by western blot, confocal microscopy and
      cytofluorometry. The mRNA levels of apoptotic mediators were assessed semi
      quantitatively by RT-PCR. Tumour-suppressor p53 trans activity was assessed in
      EMSA experiments. HDAC inhibitors were also studied in cells subjected to plasmid
      based p53 interference (p53i). KEY RESULTS: HDAC inhibitors induced cell death
      via the mitochondrial pathway of apoptosis with recruitment of Bcl-2 family
      members. Bcl-2 overexpression rendered neuroblastoma cells resistant to HDAC
      inhibitor treatment. Low concentrations of HDAC inhibitors (0.9 mM) caused a G(2)
      cell-cycle arrest and a marked upregulation of the p21/Waf1/Cip1 protein. HDAC
      inhibitors also activate the p53 protein via hyper-acetylation and nuclear re
      localization, without affecting its protein expression. Accordingly, HDAC
      inhibitor-induced cell-killing and p21/Waf1/Cip1 upregulation is impaired in p53i
      cells. CONCLUSIONS AND IMPLICATIONS: In neuroblastoma cells, HDAC inhibitors may
      overcome the resistance to classical chemotherapeutic drugs by restoring the p53
      tumour-repressor function via its hyper-acetylation and nuclear migration, events
      usually impaired in such tumours. In neuroblastoma cells, HDAC inhibitors are not
      able to induce p21/Waf1/Cip1 in the absence of a functional p53.

PMID- 18059321
TI  - Agonist-selective mechanisms of GPCR desensitization.
AB  - The widely accepted model of G protein-coupled receptor (GPCR) regulation
      describes a system where the agonist-activated receptors couple to G proteins to
      induce a cellular response, and are subsequently phosphorylated by a family of
      kinases called the G protein-coupled receptor kinases (GRKs). The GRK
      phosphorylated receptor then acts as a substrate for the binding of a family of
      proteins called arrestins, which uncouple the receptor and G protein so
      desensitizing the agonist-induced response. Other kinases, principally the second
      messenger-dependent protein kinases, are also known to play a role in the
      desensitization of many GPCR responses. It is now clear that there are subtle and
      complex interactions between GRKs and second messenger-dependent protein kinases
      in the regulation of GPCR function. Functional selectivity describes the ability
      of agonists to stabilize different active conformations of the same GPCR. With
      regard to desensitization, distinct agonist-activated conformations of a GPCR
      could undergo different molecular mechanisms of desensitization. An example of
      this is the mu opioid receptor (MOPr), where the agonists morphine and [D
      Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO) induce desensitization of the MOPr
      by different mechanisms, largely protein kinase C (PKC)- or GRK-dependent,
      respectively. This can be best explained by supposing that these two agonists
      stabilize distinct conformations of the MOPr, which are nevertheless able to
      couple to the relevant G-proteins and produce similar responses, yet are
      sufficiently different to trigger different regulatory processes. There is
      evidence that other GPCRs also undergo agonist-selective desensitization, but the
      full therapeutic consequences of this phenomenon await further detailed study.

PMID- 18059322
TI  - Activities of mixed NOP and mu-opioid receptor ligands.
AB  - BACKGROUND AND PURPOSE: Compounds that activate both NOP and mu-opioid receptors
      might be useful as analgesics and drug abuse medications. Studies were carried
      out to better understand the biological activity of such compounds. EXPERIMENTAL
      APPROACH: Binding affinities were determined on membranes from cells transfected
      with NOP and opioid receptors. Functional activity was determined by
      [(35)S]GTPgammaS binding on cell membranes and using the mouse vas deferens
      preparation in vitro and the tail flick antinociception assay in vivo. KEY
      RESULTS: Compounds ranged in affinity from SR14150, 20-fold selective for NOP
      receptors, to buprenorphine, 50-fold selective for mu-opioid receptors. In the
      [(35)S]GTPgammaS assay, SR compounds ranged from full agonist to antagonist at
      NOP receptors and most were partial agonists at mu-opioid receptors.
      Buprenorphine was a low efficacy partial agonist at mu-opioid receptors, but did
      not stimulate [(35)S]GTPgammaS binding through NOP. In the mouse vas deferens,
      each compound, except for SR16430, inhibited electrically induced contractions.
      In each case, except for N/OFQ itself, the inhibition was due to mu-opioid
      receptor activation, as determined by equivalent results in NOP receptor knockout
      tissues. SR14150 showed antinociceptive activity in the tail flick test, which
      was reversed by the opioid antagonist naloxone. CONCLUSIONS AND IMPLICATIONS:
      Compounds that bind to both mu-opioid and NOP receptors have antinociceptive
      activity but the relative contribution of each receptor is unclear. These
      experiments help characterize compounds that bind to both receptors, to better
      understand the mechanism behind their biological activities, and identify new
      pharmacological tools to characterize NOP and opioid receptors.

PMID- 18059323
TI  - Cigarette smoke inhibits macrophage sensing of Gram-negative bacteria and
      lipopolysaccharide: relative roles of nicotine and oxidant stress.
AB  - BACKGROUND AND PURPOSE: Smoking cigarettes is a major risk factor for the
      development of cardiovascular and respiratory disease. Moreover, smokers are more
      prone to infections. This has been associated with a suppression of the immune
      system by smoke. However, it is not clear how cigarette smoke affects the ability
      of immune cells to sense pathogens. Cigarette smoke contains a large number of
      molecules which may mediate responses on immune cells and of these, nicotine and
      oxidants have both been identified as inhibitory for the sensing of bacterial
      lipopolysaccharide (LPS). Nitric oxide synthase (NOS) and tumour necrosis factor
      (TNF)-alpha are both induced in macrophages on stimulation with Gram negative
      bacteria or LPS. EXPERIMENTAL APPROACH: We used murine macrophages stimulated
      with whole heat-killed bacteria or LPS. We measured output of NO (as nitrite) and
      TNFalpha, NOS protein by Western blotting and cellular oxidant stress. KEY
      RESULTS: Cigarette smoke extract suppressed the ability of murine macrophages to
      release NO, but not TNFalpha in response to whole bacteria. Cigarette smoke
      extract also inhibited nitric oxide synthase II protein expression in response to
      LPS. The effects of cigarette smoke extract on nitrite formation stimulated by
      LPS were unaffected by inhibition of nicotinic receptors with alpha-bungarotoxin
      (100 units ml(-1)). However, the effects of cigarette smoke extract on LPS
      induced nitrite formation were mimicked by hydrogen peroxide and reversed by the
      anti-oxidants N-acetyl cysteine and glutathione. CONCLUSIONS AND IMPLICATIONS: We
      suggest that cigarette smoke exerts its immunosuppressive effects through an
      oxidant-dependent and not a nicotine-dependent mechanism.

PMID- 18059325
TI  - Control of left ventricular mass by moxonidine involves reduced DNA synthesis and
      enhanced DNA fragmentation.
AB  - BACKGROUND AND PURPOSE: Left ventricular hypertrophy (LVH) is a maladaptive
      process associated with increased cardiovascular risk. Regression of LVH is
      associated with reduced complications of hypertension. Moxonidine is an
      antihypertensive imidazoline compound that reduces blood pressure primarily by
      central inhibition of sympathetic outflow and by direct actions on the heart to
      release atrial natriuretic peptide, a vasodilator and an antihypertrophic cardiac
      hormone. This study investigated the effect of moxonidine on LVH and the
      mechanisms involved in this effect. EXPERIMENTAL APPROACH: Spontaneously
      hypertensive rats were treated with several doses of moxonidine (s.c.) over 4
      weeks. Blood pressure and heart rate were continuously monitored by telemetry.
      Body weight and water and food intake were measured weekly. Measurements also
      included left ventricular mass, DNA content, synthesis, fragmentation, and
      apoptotic/anti-apoptotic pathway proteins. KEY RESULTS: The decrease in mean
      arterial pressure stabilized at approximately -10 mm Hg after 1 week of treatment
      and thereafter. Compared to vehicle-treated rats (100%), left ventricular mass
      was dose- and time-dependently reduced by treatment. This reduction remained
      significantly lower after normalizing to body weight. Moxonidine reduced left
      ventricular DNA content and inhibited DNA synthesis. DNA fragmentation
      transiently, but significantly increased at 1 week of moxonidine treatment and
      was paralleled by elevated active caspase-3 protein. The highest dose
      significantly decreased the apoptotic protein Bax and all doses stimulated anti
      apoptotic Bcl-2 after 4 weeks of treatment. CONCLUSIONS AND IMPLICATIONS: These
      studies implicate the modulation of cardiac DNA dynamics in the control of left
      ventricular mass by moxonidine in a rat model of hypertension.

PMID- 18059324
TI  - Pharmacological approaches to acute ischaemic stroke: reperfusion certainly,
      neuroprotection possibly.
AB  - Stroke is a major cause of both death and disability. However, there are no
      pharmacological treatments used in most countries other than recombinant tissue
      plasminogen activator, a thrombolytic, and this is only used in about 4% of
      patients presenting after an acute ischaemic stroke. One novel thrombolytic
      (desmoteplase) has just been reported to have failed in a Phase IIb/III trial,
      but other thrombolytics and reperfusion agents remain in development. The picture
      with neuroprotectant agents, that is compounds that act to preserve neurones
      following an acute cerebral ischaemic insult, is even more bleak. Despite the
      development of over 1,000 compounds, many proving effective in animal models of
      stroke, none has demonstrated efficacy in patients in the over 100 clinical
      trials conducted. This includes NXY-059, which was developed in accordance with
      the guidelines proposed by an academic-industry roundtable group (STAIR). This
      review examines the available data on compounds currently in development. It also
      proposes that the failure of translation between efficacy in preclinical models
      and patients is likely to terminate most current neuroprotective drug
      development. It is suggested that animal models must be made more representative
      of the patient condition (with other co-morbid conditions) and suggests that
      since stroke is primarily a cardiovascular disease with a neurological outcome,
      more research on the neurovascular unit would be valuable. New approaches on
      neuroinflammation, neurorestoration and neurorepair are also likely to gain
      prominence in the search for new drugs to treat this major clinical problem.

PMID- 18059326
TI  - Paraoxonase 1 gene transfer lowers vascular oxidative stress and improves
      vasomotor function in apolipoprotein E-deficient mice with pre-existing
      atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Transgenesis of human paraoxonase 1 (PON1), a HDL
      associated enzyme that destroys lipid peroxides, has been reported to reduce
      early atherogenesis in mice. The present study explored the therapeutic potential
      of human PON1 gene transfer in old apolipoprotein E-deficient (apoE(-/-)) mice
      with advanced atherosclerosis. EXPERIMENTAL APPROACH: ApoE(-/-) mice (18 months,
      regular chow) were transfected with PON1 adenovirus (AdPON1, n=10) or control
      adenovirus (AdRR5, n=10). Non-transfected apoE(-/-) (n=9) and C57Bl/6J (WT, n=6)
      mice served as controls. Three weeks later, plaque size and composition, and
      endothelial cell (EC) and smooth muscle cell (SMC) function were assessed in the
      aorta. KEY RESULTS: PON1 gene transfer raised total PON1 serum activity 13-15
      fold during the 3-week study period, without affecting hypercholesterolaemia or
      lesion size. However, PON1 decreased the oxLDL content of the plaque. Plaque-free
      thoracic aorta rings from apoE(-/-) mice displayed, like rings from WT mice,
      complete relaxation to acetylcholine (ACh, 86+/-2%), ATP (90+/-2%) or UTP (83+/
      3%). In contrast, in plaque-bearing segments amplitude (55+/-7%, 68+/-8%, 52+/-8%
      respectively) and sensitivity were decreased. EC function was completely (ATP,
      UTP) or largely (ACh) restored by AdPON1. Furthermore, apoE(-/-) SMCs released
      less intracellular calcium than WT upon sarco-endoplasmic reticulum calcium
      ATPase (SERCA) inhibition by cyclopiazonic acid. This defect was also restored by
      AdPON1 transfection. CONCLUSIONS AND IMPLICATIONS: These data indicate that
      AdPON1 gene transfer improved vascular wall oxidative stress, EC function, and
      SMC Ca(2+) homeostasis in segments with pre-existing atherosclerosis,
      independently of an effect on plaque size.

PMID- 18059327
TI  - Effects of zileuton and montelukast in mouse experimental spinal cord injury.
AB  - BACKGROUND AND PURPOSE: 5-lipoxygenase (5-LO) is the key enzyme in leukotriene
      (LT) biosynthesis from arachidonic acid (AA). Here, we examined the role of the 5
      LO-product, cysteinyl-LT (Cys-LT), with a 5-LO inhibitor (zileuton) and a Cys-LT,
      receptor antagonist (montelukast), in the inflammatory response and tissue injury
      associated with spinal cord injury (SCI). EXPERIMENTAL APPROACH: SCI was induced
      in mice by the application of vascular clips to the dura via a two-level T6 to T7
      laminectomy for 1 min. Cord inflammation was assessed histologically and by
      measuring inflammatory mediators (ELISA) and apoptosis by annexin V, TUNEL, Fas
      ligand staining and Bax and Bcl-2 expression (immunohistochemistry and western
      blots). Motor function in hindlimbs was assessed by a locomotor rating scale, for
      10 days after cord injury. KEY RESULTS: SCI in mice resulted in tissue damage,
      oedema, neutrophil infiltration, apoptosis, tumour necrosis-alpha (TNF-alpha) and
      cyclooxygenase-2 (COX-2) expression, prostaglandin E(2) (PGE(2)) and leukotriene
      B(4) (LTB(4)) production, and extracellular signal-regulated kinase 1/2 (ERK1/2)
      phosphorylation in injured tissue. Treatment of the mice with zileuton or
      montelukast reduced the spinal cord inflammation and tissue injury, neutrophil
      infiltration, TNF-alpha, COX-2 and pERK1/2 expression, PGE(2) and LTB(4)
      production, and apoptosis. In separate experiments, zileuton or montelukast
      significantly improved the recovery of limb function over 10 days. CONCLUSIONS
      AND IMPLICATIONS: Zileuton and montelukast produced a substantial reduction of
      inflammatory events associated with experimental SCI. Our data underline the
      important role of 5-LO and Cys-LT in neurotrauma.

PMID- 18059330
TI  - Hematopoietic cell transplantation for thalassemia and sickle cell disease: past,
      present and future.
AB  - beta-Thalassemia major and sickle cell disease (SCD) are among the most common
      hereditary disorders worldwide. The supportive treatment of beta-thalassemia
      major requires chronic, life-long RBC transfusions, which cause progressive iron
      overload and the potential for impaired endocrine, cardiac and hepatic function.
      The phenotype of thalassemia major is reliably predicted by its genotype. In
      contrast, SCD is a variable genetic disease caused by a single amino acid
      substitution in the beta chain of human hemoglobin. Manifestations of SCD are
      quite varied, but generally result from the tendency of Hb S to irreversibly
      polymerize under physiologic stressors such as hypoxemia and acidosis. The
      polymerization causes perturbations in the erythrocyte integrity that promote
      vaso-occlusion and which manifest as clinical events such as severe painful
      episodes, acute chest syndrome, splenic infarction, stroke and avascular necrosis
      of target joints. The only cure proved for these disorders is correction of the
      genetic defect by allogeneic hematopoietic cell transplantation (HCT). We
      illustrate the pediatric experience of HCT for hemoglobinopathies and discuss how
      these results affect future therapeutic decisions in children who inherit these
      disorders.

PMID- 18059331
TI  - p19/Arf and p53 suppress sentinel lymph node lymphangiogenesis and carcinoma
      metastasis.
AB  - The ability of tumor cells to metastasize is increasingly viewed as an
      interaction between the primary tumor and host tissues. Deletion of the p19/Arf
      or p53 tumor suppressor genes accelerates malignant progression and metastatic
      spread of 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13
      acetate (TPA)-induced squamous cell carcinomas, providing a model system to
      address mechanisms of metastasis. Here, we show that benign pre-metastatic
      papillomas from wild-type mice trigger lymphangiogenesis within draining lymph
      nodes, whereas there is no growth of primary tumor lymphatic vessels. Lymph node
      lymphangiogenesis is greatly accelerated in papilloma-bearing p19/Arf- or p53
      deficient mice, which coincides with the greater propensity of these tumors to
      progress to carcinomas and to metastasize. The extent of accumulation of B cells
      within the tumor-draining lymph nodes of wild-type mice predicted the level of
      lymph node lymphangiogenesis and metastatic potential. Arf or p53 deficiency
      strongly accelerated lymph node immune cell accumulation, in a manner that was
      associated with the extent of lymph node lymphatic sinus growth. This immune cell
      accumulation and lymph node lymphangiogenesis phenotype identifies host anti
      tumor responses that could drive metastatic spread of cancers via the lymphatics.

PMID- 18059328
TI  - Role of the brain-derived neurotrophic factor at glutamatergic synapses.
AB  - The neurotrophin brain-derived neurotrophic factor (BDNF) plays an important role
      in the activity-dependent regulation of synaptic structure and function,
      particularly of the glutamatergic synapses. BDNF may be released in the mature
      form, which activates preferentially TrkB receptors, or as proBDNF, which is
      coupled to the stimulation of the p75(NTR). In the mature form BDNF induces rapid
      effects on glutamate release, and may induce short- and long-term effects on the
      postsynaptic response to the neurotransmitter. BDNF may affect glutamate receptor
      activity by inducing the phosphorylation of the receptor subunits, which may also
      affect the interaction with intracellular proteins and, consequently, their
      recycling and localization to defined postsynaptic sites. Stimulation of the
      local protein synthesis and transcription activity account for the delayed
      effects of BDNF on glutamatergic synaptic strength. Several evidences show
      impaired synaptic plasticity of glutamatergic synapses in diseases where
      compromised BDNF function has been observed, such as Huntington's disease,
      depression, anxiety, and the BDNF polymorphism Val66Met, suggesting that
      upregulating BDNF-activated pathways may be therapeutically relevant. This review
      focuses on recent advances in the understanding of the regulation of the
      glutamatergic synapse by BDNF, and its implications in synaptic plasticity.

PMID- 18059332
TI  - A novel role for the retinoic acid-catabolizing enzyme CYP26A1 in Barrett's
      associated adenocarcinoma.
AB  - Vitamin A deficiency is associated with carcinogenesis, and upregulation of
      CYP26A1, a major retinoic acid (RA)-catabolizing enzyme, has recently been shown
      in cancer. We have previously demonstrated alterations of RA biosynthesis in
      Barrett's oesophagus, the precursor lesion to oesophageal adenocarcinoma. The
      aims of this study were to determine CYP26A1 expression levels and functional
      effects in Barrett's associated carcinogenesis. Retinoic acid response element
      reporter cells were used to determine RA levels in non-dysplastic and dysplastic
      Barrett's cell lines and endoscopic biopsies. CYP26A1 expression levels, with or
      without induction by RA and lithocholic acid, were determined by quantitative
      reverse transcriptase-PCR (RT-PCR) and immunohistochemistry. CYP26A1 promoter
      activity was determined by a luciferase reporter construct. CYP26A1 was stably
      overexpressed in GihTERT cells, which were evaluated for gene-expression changes
      (pathway array and quantitative RT-PCR), cellular proliferation (cytometric DNA
      profile and colorimetric assay) and invasion (in vitro matrigel assay) with or
      without the CYP inhibitor ketaconazole. RA levels decreased progressively with
      the degree of dysplasia (P<0.05) and were inversely correlated with CYP26A1 gene
      levels and activity (P<0.01). CYP26A1 expression was increased synergistically by
      RA and lithocholic acid (P<0.05). Overexpression of CYP26A1 led to induction of c
      Myc, epidermal growth factor receptor and matrix metalloproteinase 3 as well as
      downregulation of tissue inhibitor metalloproteinase 1 and 3. Functional effects
      of CYP26A1 overexpression were increased proliferation (P<0.01) and invasion in
      vitro (P<0.01), which were inhibited by ketaconazole. Overexpression of CYP26A1
      causes intracellular RA depletion and drives the cell into a highly proliferative
      and invasive state with induction of other known oncogenes.

PMID- 18059333
TI  - A CRM1-mediated nuclear export signal governs cytoplasmic localization of BRCA2
      and is essential for centrosomal localization of BRCA2.
AB  - Germ-line mutations of the BRCA2 gene cause inherited susceptibility to breast
      and ovarian cancers. BRCA2 contains two nuclear localization signals,
      predominantly localizes in the nucleus and plays significant roles in DNA double
      strand break repair. Recently, we reported that BRCA2 localizes to the
      centrosomes during the S and early M phases of the cell cycle. In this study, for
      the first time, we identified a functional nuclear export sequence (NES1;
      (1383)DLSDLTFLEVA(1393)) in BRCA2. The green fluorescent protein (GFP)-NES1
      fusion protein was localized in the cytoplasm and could be blocked by the
      chromosomal region maintenance 1-specific export inhibitor leptomycin B. Mutation
      of a leucine residue in the NES1 motif to alanine (L1384A) resulted in both
      cytoplasmic and nuclear localization of the GFP-NES1 fusion protein and a nuclear
      accumulation of ectopic full-length BRCA2-FLAG. Moreover, treatment of cells with
      leptomycin B decreased centrosomal localization of BRCA2. Finally, by
      microinjection of an anti-BRCA2 antibody into the cytoplasm of HeLa S3 cells, we
      found that depletion of normal BRCA2 proteins in the cytoplasm leads to
      centrosome amplification and binucleated cells. Our results suggest that
      disruption of the NES function by genetic changes results in deregulation of
      BRCA2 export, which ultimately leads to centrosome disorder.

PMID- 18059334
TI  - Tyrosine phosphorylation regulates nuclear translocation of PKCdelta.
AB  - PKCdelta is essential for apoptosis, but regulation of the proapoptotic function
      of this ubiquitous kinase is not well understood. Nuclear translocation of
      PKCdelta is necessary and sufficient to induce apoptosis and is mediated via a C
      terminal bipartite nuclear localization sequence. However, PKCdelta is found
      predominantly in the cytoplasm of nonapoptotic cells, and the apoptotic signal
      that activates its nuclear translocation is not known. We show that in salivary
      epithelial cells, phosphorylation at specific tyrosine residues in the N-terminal
      regulatory domain directs PKCdelta to the nucleus where it induces apoptosis.
      Analysis of each tyrosine residue in PKCdelta by site-directed mutagenesis
      identified two residues, Y64 and Y155, as essential for nuclear translocation.
      Suppression of apoptosis correlated with suppressed nuclear localization of the Y
      --> F mutant proteins. Moreover, a phosphomimetic PKCdelta Y64D/Y155D mutant
      accumulated in the nucleus in the absence of an apoptotic signal. Forced nuclear
      accumulation of PKCdelta-Y64F and Y155F mutant proteins, by attachment of an SV40
      nuclear localization sequence, fully reconstituted their ability to induce
      apoptosis, indicating that tyrosine phosphorylation per se is not required for
      apoptosis, but for targeting PKCdelta to the nucleus. We propose that
      phosphorylation/dephosphorylation of PKCdelta in the regulatory domain functions
      as a switch to promote cell survival or cell death.

PMID- 18059335
TI  - A novel function for HSF1-induced mitotic exit failure and genomic instability
      through direct interaction between HSF1 and Cdc20.
AB  - Although heat-shock factor (HSF) 1 is a known transcriptional factor of heat
      shock proteins, other pathways like production of aneuploidy and increased
      protein stability of cyclin B1 have been proposed. In the present study, the
      regulatory domain of HSF1 (amino-acid sequence 212-380) was found to interact
      directly with the amino-acid sequence 106-171 of Cdc20. The association between
      HSF1 and Cdc20 inhibited the interaction between Cdc27 and Cdc20, the
      phosphorylation of Cdc27 and the ubiquitination activity of anaphase-promoting
      complex (APC). The overexpression of HSF1 inhibited mitotic exit and the
      degradations of cyclin B1 and securin, which resulted in production of aneuploidy
      and multinucleated cells, but regulatory domain-deficient HSF1 did not. Moreover,
      HSF1-overexpressing cells showed elevated levels of micronuclei and genomic
      alteration. The depletion of HSF1 from cells highly expressing HSF1 reduced
      nocodazole-mediated aneuploidy in cells. These findings suggest a novel function
      of HSF1 frequently overexpressed in cancer cells, to inhibit APC/C activity by
      interacting with Cdc20, and to result in aneuploidy development and genomic
      instability.

PMID- 18059329
TI  - Proteinases and signalling: pathophysiological and therapeutic implications via
      PARs and more.
AB  - Proteinases like thrombin, trypsin and tissue kallikreins are now known to
      regulate cell signaling by cleaving and activating a novel family of G-protein
      coupled proteinase-activated receptors (PARs 1-4) via exposure of a tethered
      receptor-triggering ligand. On their own, short synthetic PAR-selective PAR
      activating peptides (PAR-APs) mimicking the tethered ligand sequences can
      activate PARs 1, 2 and 4 and cause physiological responses both in vitro and in
      vivo. Using the PAR-APs as sentinel probes in vivo, it has been found that PAR
      activation can affect the vascular, renal, respiratory, gastrointestinal,
      musculoskeletal and nervous systems (both central and peripheral nervous system)
      and can promote cancer metastasis and invasion. In general, responses triggered
      by PARs 1, 2 and 4 are in keeping with an innate immune inflammatory response,
      ranging from vasodilatation to intestinal inflammation, increased cytokine
      production and increased or decreased nociception. Further, PARs have been
      implicated in a number of disease states, including cancer and inflammation of
      the cardiovascular, respiratory, musculoskeletal, gastrointestinal and nervous
      systems. In addition to activating PARs, proteinases can cause hormone-like
      effects by other signalling mechanisms, like growth factor receptor activation,
      that may be as important as the activation of PARs. We, therefore, propose that
      the PARs themselves, their activating serine proteinases and their associated
      signalling pathways can be considered as attractive targets for therapeutic drug
      development. Thus, proteinases in general must now be considered as 'hormone
      like' messengers that can signal either via PARs or other mechanisms.

PMID- 18059336
TI  - Ets-2 and p160 proteins collaborate to regulate c-Myc in endocrine resistant
      breast cancer.
AB  - Associations between p160 coactivator proteins and endocrine resistance have been
      described. Though thought to primarily interact with steroid receptors, the p160
      proteins can also interact with non-nuclear receptor transcription factors
      including the MAP kinase effector proteins Ets. Here, we observed that in breast
      cancer cells resistant and insensitive to endocrine treatment, the growth factor
      EGF induced Ets-2 but not Ets-1 transcriptional regulation of the oncogene myc.
      Ets-2 regulation of myc was found to be reliant on the p160 proteins SRC-1 and
      SRC-3. In support of these molecular observations, strong associations were
      observed between the transcription factor, Ets-2 and its coactivator SRC-1
      (P<0.01) and the target gene myc (P<0.0001) in a cohort of breast cancer patients
      with locally advanced disease. Expression of Ets-2, SRC-1 and c-Myc individually
      all associated with reduced disease-free survival (P<0.001, P<0.001 and P=0.002
      respectively). There was no association between SRC-3 and disease-free survival
      (P=0.707). SRC-1 can utilize MAP kinase effector transcription factor Ets-2 to
      regulate the production of the oncogene myc. These signalling mechanisms may be
      important in the development of steroid resistant/independent breast cancer.

PMID- 18059337
TI  - High-resolution array CGH analysis of salivary gland tumors reveals fusion and
      amplification of the FGFR1 and PLAG1 genes in ring chromosomes.
AB  - We have previously identified a subgroup of pleomorphic salivary gland adenomas
      with ring chromosomes of uncertain derivation. Here, we have used spectral
      karyotyping (SKY), fluorescence in situ hybridization (FISH) and high-resolution
      oligonucleotide array-CGH to determine the origin and content of these rings and
      to identify genes disrupted as a result of ring formation. Of 16 tumors with
      rings, 11 were derived from chromosome 8, 3 from chromosome 5 and 1 each from
      chromosomes 1, 6 and 9. Array-CGH revealed that 10/11 r(8) consisted of
      amplification of a 19 Mb pericentromeric segment with recurrent breakpoints in
      FGFR1 in 8p12 and in PLAG1 in 8q12.1. Molecular analyses revealed that ring
      formation consistently generated novel FGFR1-PLAG1 gene fusions in which the 5'
      part of FGFR1 is linked to the coding sequence of PLAG1. An alternative mechanism
      of PLAG1 activation was found in tumors with copy number gain of an intact PLAG1
      gene. Rings derived from chromosomes 1, 5, 6 or 9 did not result in gene fusions,
      but rather resulted in losses indicative of the involvement of putative tumor
      suppressor genes on 8p, 5p, 5q and/or 6q. Our findings also reveal a novel
      mechanism by which FGFR1 contributes to oncogenesis and further illustrate the
      versatility of the FGFR1 and PLAG1 genes in tumorigenesis.

PMID- 18059338
TI  - p38 MAPK plays an essential role in apoptosis induced by photoactivation of a
      novel ethylene glycol porphyrin derivative.
AB  - In this study, we provide evidence that photostimulation of various cancer cells
      preloaded with a new photosensitizing compound, tetrakis-meso-(4-ethyleneglycol
      2,3,5,6-tetrafluorophenyl) porphyrin (PORF-TEG), results in rapid activation of
      the cell death machinery. PORF-TEG, although primarily localized in lysosomes,
      induces mitochondria-driven apoptosis. The induction of apoptosis is accompanied
      by immediate and sustained activation of p38 mitogen-activated protein kinase
      (MAPK) and transient activation of c-Jun N-terminal kinase (JNK). Conversely, the
      inhibition of p38 by PD 169316 or SB202190 and by the p38alpha dominant-negative
      mutant as well as the deletion of the p38alpha gene (MEFs-KO) protected cells
      from apoptosis, whereas inhibition of JNK did not. Activation of the p38
      signaling pathway occurs upstream of caspase activation. In addition,
      preincubation of cells with scavengers of reactive oxygen species attenuated p38
      and caspase activation and increased cell survival, thus connecting reactive
      oxygen species formation with the activation of the p38 pathway. Later events
      included degradation of Bcl-2, activation of tBid, and cleavage of Bad and Mcl-1.
      The data suggest a key role for p38 MAPK in PORF-TEG-photoinduced apoptosis.

PMID- 18059339
TI  - The zinc-finger transcription factor, early growth response 3, mediates VEGF
      induced angiogenesis.
AB  - Early growth response 3 (Egr3) is a member of a zinc-finger transcription factor
      subfamily, which we previously found to be strongly upregulated by vascular
      endothelial growth factor (VEGF)-A in an oligonucleotide microarray screen of
      endothelial cells. Here, we show that Egr3 is the predominant Egr family member
      upregulated by VEGF in endothelial cells at 45 min, and that VEGF induced a rapid
      increase in Egr-dependent transcriptional activation mediated via its major
      signalling receptor, VEGFR2/KDR, and the protein kinase C (PKC) pathway. VEGF
      induced Egr3 gene expression was also mediated in part via a PKC-dependent
      activation of protein kinase D. Inhibition of Egr3 gene expression by RNA
      interference was effective in inhibiting basal and VEGF-induced Egr3 gene
      expression, and it also inhibited VEGF-mediated endothelial cell proliferation,
      migration and tubulogenesis. These findings indicate that Egr3 has an essential
      downstream role in VEGF-mediated endothelial functions leading to angiogenesis
      and may have particular relevance for adult angiogenic processes involved in
      vascular repair and neovascular disease.

PMID- 18059340
TI  - Interaction with PI3-kinase contributes to the cytotoxic activity of apoptin.
AB  - Apoptin, a small protein from the chicken anemia virus, has attracted attention
      because of its specificity in killing tumor cells. Localization of apoptin in the
      nucleus of tumor cells has been shown to be vital for proapoptotic activity,
      however, targeted expression of apoptin in the nucleus of normal cells does not
      harm the cells, indicating that nuclear localization of apoptin is insufficient
      for its cytotoxicity. Here, we demonstrate for the first time that apoptin
      interacts with the SH3 domain of p85, the regulatory subunit of phosphoinositide
      3-kinase (PI3-K), through its proline-rich region. Apoptin derivatives devoid of
      this proline-rich region do not interact with p85, are unable to activate PI3-K,
      and show impaired apoptosis induction. Moreover, apoptin mutants containing the
      proline-rich domain are sufficient to elevate PI3-K activity and to induce
      apoptosis in cancer cells. Downregulation of p85 leads to nuclear exclusion of
      apoptin and impairs cell death induction, indicating that interaction with the
      p85 PI3-K subunit essentially contributes to the cytotoxic activity of apoptin.

PMID- 18059341
TI  - Constitutive activation of the Raf-MAPK pathway causes negative feedback
      inhibition of Ras-PI3K-AKT and cellular arrest through the EphA2 receptor.
AB  - The Raf-mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3
      kinase (PI3K)-AKT pathways are two downstream effectors of the small GTPase Ras.
      Although both pathways are positively regulated by Ras, the Raf-MAPK and PI3K-AKT
      pathways have been shown to control opposing functions within the cell,
      suggesting a need for cross-talk regulation. The PI3K-AKT pathway can inhibit the
      Raf-MAPK pathway directly during processes such as muscle differentiation. Here
      we describe the ability of the Raf-MAPK pathway to negatively regulate the PI3K
      AKT pathway during cellular arrest. Constitutive activation of Raf or methyl
      ethyl ketone 1 (MEK1) leads to inhibition of AKT and cellular arrest.
      Furthermore, we show that activation of Raf-MEK1 signaling causes negative
      feedback inhibition of Ras through the ephrin receptor EphA2. EphA2-mediated
      negative feedback inhibition is required for Raf-induced AKT inhibition and cell
      cycle arrest, therefore establishing the inhibition of the Ras-PI3K-AKT pathway
      as a necessary event for the Raf-MEK1-regulated cellular arrest.

PMID- 18059342
TI  - Partial functional overlap of the three ras genes in mouse embryonic development.
AB  - In mammals, three ras genes, H-ras, N-ras and K-ras, encode homologous but
      distinct 21-kDa Ras proteins. We examined the in vivo functional relationship of
      the three ras genes in mouse embryonic development by investigating the
      phenotypes of mice deficient in one or multiple ras genes. H-ras-/- mice and N
      ras-/- mice as well as a substantial proportion of H-ras-/-/N-ras-/- mice
      expressing only the K-ras gene were viable, while K-ras-/- mice were
      embryonically lethal, as have been reported previously. N-ras-/-/K-ras+/- mice
      died neonatally, while H-ras-/-/K-ras-/- embryos died much earlier than K-ras
      homozygous mutant fetuses. To further investigate the functional relationship of
      the ras genes in embryonic development, we introduced a human H-ras transgene
      into single or multiple ras mutant mice and found that the transgene rescued
      mice, including triple ras mutants, from embryonic lethality in association with
      correction of thin ventricular walls of the heart in null K-ras mutant mice. In
      situ hybridization revealed that the expression of the H-ras transgene on
      embryonic day E13.5 and E15.5 was more intense in major organs, including the
      heart, than those of endogenous ras genes. We therefore conclude that the
      functions of the ras genes are partially overlapping in mouse embryonic
      development.

PMID- 18059343
TI  - Differential motility of p190bcr-abl- and p210bcr-abl-expressing cells:
      respective roles of Vav and Bcr-Abl GEFs.
AB  - The chimeric oncogene Bcr-Abl is known to induce autonomous motility of leukemic
      cells. We show here that p210(bcr-abl) responsible for chronic myelogenous
      leukemia induces an amoeboid type of motility while p190(bcr-abl), associated
      with acute lymphoid leukemia, induces a rolling type of motility. We previously
      reported that p210(bcr-abl) activates RhoA and Rac1, while p190(bcr-abl) although
      devoid of a Dbl-homology (DH) domain activates Rac1, but not RhoA. We
      investigated the regulation of GDP/GTP exchange factor (GEF) activities in the
      Bcr-Abl complex. For that purpose, different GEF activity mutants of Vav and of
      Bcr-Abl were constructed and stably transfected in Ba/F3 cells. Using these
      mutants, we demonstrate that RhoA is exclusively activated by the DH domain of
      p210(bcr-abl), while Rac1 activation is mostly due to Vav. Inhibition of Rac1 by
      Vav GEF mutant leads to immobilization of cells. Vav depletion using shRNA also
      induces immobilization of cells and suppression of GTP-bound Rac1. RhoA
      inactivation induces the specific loss of amoeboid movements. These results
      suggest that Rac1 activation by Vav triggers the motility of Bcr-Abl-expressing
      Ba/F3 cells, while the specific amoeboid mode of motility induced by p210(bcr
      abl) is a consequence of RhoA activation.

PMID- 18059345
TI  - Surgeon's core values: legitimizing the team concept in surgery.

PMID- 18059344
TI  - The proapoptotic effects of sulindac, sulindac sulfone and indomethacin are
      mediated by nucleolar translocation of the RelA(p65) subunit of NF-kappaB.
AB  - Understanding the mechanisms that underlie the antitumour activity of non
      steroidal anti-inflammatory drugs (NSAIDs) against colorectal cancer will allow
      the development of more effective and specific chemopreventative agents.
      Modulation of the NF-kappaB pathway has been implicated as a key effector of the
      antitumour effect of aspirin, but the effects of non-aspirin NSAIDs on this
      pathway have yet to be fully defined. Here, we demonstrate that sulindac,
      sulindac sulfone and indomethacin activate the NF-kappaB pathway in colorectal
      cancer cells, as determined by western blot analysis of cytoplasmic levels of
      IkappaBalpha and immunocytochemical analysis of nuclear NF-kappaB/RelA.
      Furthermore, we show that all of these NSAIDs induce nucleolar translocation of
      the RelA subunit of NF-kappaB. Using RelA deleted for the previously described
      nucleolar localization signal, we demonstrate that this response is causally
      involved in the apoptotic effects of these agents. Finally, we demonstrate that
      NSAID-mediated nucleolar translocation of RelA is associated with downregulation
      of NF-kappaB-driven transcription and of the NF-kappaB target gene, ICAM-1. These
      data identify nucleolar translocation of RelA and the associated repression of
      the NF-kappaB-driven transcription as a central molecular mechanism of NSAID
      mediated growth inhibition and apoptosis. As well as providing new understanding
      of the molecular determinants of RelA function, these findings also have
      relevance to the development of novel chemotherapeutic and chemopreventative
      agents.

PMID- 18059346
TI  - Permanent prostate seed brachytherapy: a current perspective on the evolution of
      the technique and its application.
AB  - This Review highlights current areas of controversy and development in the field
      of transperineal permanent prostate seed implantation brachytherapy (PPI), in
      particular the technological evolution of PPI treatment planning that has led to
      intra-operative treatment planning and execution, the use of MRI spectroscopy and
      ultrasonography to target intraprostatic tumor foci, and the introduction of
      (131)Cs as a new PPI isotope. Here we present a comprehensive review of mature
      data for PPI monotherapy and PPI combined with supplemental external beam
      radiation therapy, and a critical discussion of issues pertinent to supplemental
      EBRT. We also present our current policies in the treatment of prostate cancer at
      the University of California, San Francisco.

PMID- 18059347
TI  - Management of renal stone disease in obese patients.
AB  - Obesity represents an increasing burden to health care resources. Nephrolithiasis
      is associated with obesity and type 2 diabetes and the consumption of diets rich
      in protein, fat and carbohydrates; this article addresses some of the
      pathophysiological mechanisms associated with stone formation in these patients.
      Management of stone disease can be more difficult in obese patients; even
      diagnosis can be problematic because imaging techniques are less sensitive in
      these patients. Treatment with extracorporeal shockwave lithotripsy and surgery
      in obese patients can be challenging, and outcome data for the different
      treatments are discussed in this Review.

PMID- 18059348
TI  - Mechanisms of Disease: biomarkers and molecular targets from microarray gene
      expression studies in prostate cancer.
AB  - Molecular biomarkers can serve as useful diagnostic markers, as prognostic
      markers for predicting clinical behavior, or as targets for new therapeutic
      strategies. Application of expression microarray technology, which allows the
      expression of all or most of the genes in the human genome to be analyzed
      simultaneously, has dramatically enhanced the discovery of prostate cancer
      biomarkers. The diagnostic markers identified include AMACR (alpha-methylacyl CoA
      racemase), a protein that has already been translated into clinical use as an aid
      in distinguishing prostate cancer from benign disease. Individual genes, such as
      the polycomb gene EZH2 whose expression indicates poor survival, have been
      identified. The power of microarray technology is that it has allowed the
      identification of gene signatures (each composed of multiple genes) that might
      provide improved prediction of clinical outcomes in human prostate cancer. The
      development of a new method for analyzing expression microarray data, called
      COPA, has led to the discovery of TMPRSS2-ERG gene fusion involvement in the
      development of prostate cancer, while expression analysis of castration-resistant
      prostate cancer has suggested the use of novel therapeutic approaches for
      advanced disease. Despite these successes, there are limitations in the
      application of microarray technology to prostate cancer; for example, unlike with
      other cancers, this approach has failed to provide a consistent unsupervised
      classification of the disease. Overcoming the reasons for these failures
      represents a major challenge for future research endeavors.

PMID- 18059349
TI  - Rational approach to the treatment of a patient with a small renal cortical
      tumor.
AB  - BACKGROUND: A 64-year-old man with a history of hypertension and type II diabetes
      mellitus presented to his primary care physician for his annual health
      examination. Renal ultrasonography revealed a solid right renal mass, which was
      confirmed by MRI. The initial consultant recommended laparoscopic radical
      nephrectomy. The patient sought a second opinion. INVESTIGATIONS: Physical
      examination, baseline serum creatinine level, urine cytology, CT urogram and
      renal ultrasonography. DIAGNOSIS: Centrally located subcortical tumor arising
      from the renal parenchyma. MANAGEMENT: Open partial nephrectomy. There were no
      intraoperative complications and the patient's postoperative course was
      uneventful.

PMID- 18059351
TI  - Celebrity cells.

PMID- 18059353
TI  - Normal brain development in importin-alpha5 deficient-mice.

PMID- 18059355
TI  - Leading the charge.
AB  - Collective cell invasion into the extracellular matrix (ECM) has been observed in
      malignant tumours and in tissue morphogenesis. To achieve this, leading cells
      trigger both proteolytic and structural modifications of the ECM to create
      channels that precede progressively widening chains of following cells.

PMID- 18059356
TI  - Ring around the genes.
AB  - How is RNA Polymerase II (RNAP) regulated at poised loci in embryonic stem cells?
      Recent work provides new insights into Ring1-mediated transcriptional control of
      this important subset of developmental regulatory genes.

PMID- 18059357
TI  - Much HUBbub about stem-cell niches.
AB  - Stem cells, and the microenvironment or 'niche' that influences them, must often
      reside in a particular location within a tissue to perform their function.
      Integrin-mediated adhesion is now shown to regulate the location of the stem-cell
      niche in the Drosophila testis.

PMID- 18059358
TI  - Entosis: cell death by invasion.

PMID- 18059361
TI  - Differentially expressed genes in a porcine adult hepatic stem-like cell line and
      their expression in developing and regenerating liver.
AB  - To identify differentially expressed genes in adult hepatic stem cells, we
      performed suppression-subtractive hybridization (SSH) between adult porcine
      hepatic stem-like cells (HSLCs) and hepatocytes, and the expression of selected
      genes was assessed in porcine fetal livers and regenerating liver in an 80%
      hepatectomy model. SSH and subsequent differential screening selected 39 clones
      that were expressed differentially in HSLCs, including six known genes, 10
      unknown genes, one unidentified gene and some chimeric fragments. Four of these
      genes showed significantly higher expression in HSLCs than in mature hepatocytes:
      anti-leukoproteinase, matrix Gla protein, amyloid-beta precursor protein (APP)
      and dickkopf-3 (DKK-3). Among them, the mRNA expression of APP and DKK-3 was
      significantly higher in fifth GW fetal liver than in seventh and thirteenth GW
      fetal and adult livers, unlike the expression patterns of alpha-fetoprotein (AFP)
      or albumin. These mRNAs were detected in the parenchyma of fifth GW fetal liver,
      whereas in normal adult liver possible expression was limited to the periportal
      area. On the other hand, immunohistochemistry, Masson's trichrome staining and
      silver impregnation demonstrated APP and DKK-3 proteins in fifth GW fetal liver
      in which intralobular bile ducts and hepatic plates had not completely developed.
      DKK-3 and AFP mRNAs were upregulated on the seventh day (7D) after 80%
      hepatectomy. In the liver tissue, DKK-3 and AFP proteins were detected in
      mesenchymal cells in the periportal area and parenchyma, respectively. These data
      for DKK-3 expression in adult livers suggest the possible presence of adult HSLCs
      in the periportal area. The pattern of histological staining suggested that 7D
      liver was in the process of regeneration, showing a character similar to the
      fifth GW fetal liver. It is speculated that DKK-3 is upregulated in immature and
      developing livers, and has possible involvement in hepatic differentiation and
      liver regeneration.

PMID- 18059362
TI  - Gene silencing of TSPYL5 mediated by aberrant promoter methylation in gastric
      cancers.
AB  - DNA methylation is crucial for normal development, but gene expression altered by
      DNA hypermethylation is often associated with human diseases, especially cancers.
      The gene TSPYL5, encoding testis-specific Y-like protein, was previously
      identified in microarray screens for genes induced by the inhibition of DNA
      methylation and histone deacetylation in glioma cell lines. The TSPYL5 showed a
      high frequency of DNA methylation-mediated silencing in both glioma cell lines
      and primary glial tumors. We now report that TSPYL5 is also inactivated by DNA
      methylation and could be a putative epigenetic target gene in gastric cancers. We
      found that the expression of TSPYL5 mRNA was frequently downregulated and
      inversely correlated with DNA methylation in seven out of nine gastric cancer
      cell lines. TSPYL5 mRNA expression was also restored after treating with a DNA
      methyltransferase inhibitor. In primary gastric tumors, methylation-specific PCR
      results in 23 of the 36 (63.9%) cases revealed that the hypermethylation at CpG
      islands of the TSPYL5 was detectable at a high frequency. Furthermore, TSPYL5
      suppressed the growth of gastric cancer cells as demonstrated by a colony
      formation assay. Thus, strong associations between TSPYL5 expression and
      hypermethylation were observed, and aberrant methylation at a CpG island of
      TSPYL5 may play an important role in development of gastric cancers.

PMID- 18059363
TI  - Epithelial-mesenchymal transition contributes to portal tract fibrogenesis during
      human chronic liver disease.
AB  - The relationship between bile duct damage and portal fibrosis in chronic liver
      diseases remains unclear. This study was designed to show whether human
      intrahepatic biliary epithelial cells can undergo epithelial-mesenchymal cell
      transition, thereby directly contributing to fibrogenesis. Primary human
      cholangiocytes were stimulated with transforming growth factor-beta (TGFbeta) or
      TGFbeta-presenting T cells and examined for evidence of transition to a
      mesenchymal phenotype. Liver sections were labelled to detect antigens associated
      with biliary epithelial cells (cytokeratin 7 and 19 and E-cadherin), T cells
      (CD8), epithelial-mesenchymal transition (S100A4, vimentin and matrix
      metalloproteinase-2 (MMP-2)), myofibroblasts (alpha-smooth muscle actin) and
      intracellular signal-transduction mediated by phosphorylated (p)Smad 2/3; in situ
      hybridisation was performed to detect mRNA encoding TGFbeta and S100A4.
      Stimulation of cultured cells with TGFbeta induced the expression of pSmad2/3,
      S100A4 and alpha-smooth muscle actin; these cells became highly motile. Although
      normal bile ducts expressed ALK5 (TGFbeta RI), low levels of TGFbeta mRNA and
      nuclear pSmad2/3, they did not express S100A4, vimentin or MMP-2. However,
      TGFbeta mRNA and nuclear pSmad2/3 were strongly expressed in damaged ducts, which
      also expressed S100A4, vimentin and MMP-2. Fibroblast-like cells which expressed
      S100A4 were present around many damaged bile ducts. Cells in the 'ductular
      reaction' expressed both epithelial and mesenchymal markers together with high
      levels of TGFbeta mRNA and pSmad2/3. In conclusion, the cells forming small- and
      medium-sized bile ducts and the ductular reaction undergo EMT during chronic
      liver diseases, resulting in the formation of invasive fibroblasts; this process
      may be driven by a response to local TGFbeta, possibly presented by infiltrating
      T cells.

PMID- 18059364
TI  - A novel and simple cell-based detection system with a collagen-encapsulated B
      lymphocyte cell line as a biosensor for rapid detection of pathogens and toxins.
AB  - Cell-based biosensors (CBBs) are becoming important tools for biosecurity
      applications and rapid diagnostics in food microbiology for their unique
      capability of detecting physiologically hazardous materials. A multi-well plate
      based biosensor containing B-cell hybridoma, Ped-2E9, encapsulated in type I
      collagen matrix, was developed for rapid detection of viable cells of pathogenic
      Listeria, the toxin listeriolysin O, and the enterotoxin from Bacillus species.
      This sensor measures the alkaline phosphatase release from infected Ped-2E9 cells
      colorimetrically. Pathogenic L. monocytogenes cells and toxin preparations from
      L. monocytogenes or B. cereus showed cytotoxicity ranging from 24 to 98% at 3-6 h
      postinfection. In contrast, nonpathogenic L. innocua (F4247) and B. subtilis
      induced minimal cytotoxicity, ranging only 0.4-7.6%. Laser scanning cytometry and
      cryo-nano scanning electron microscopy confirmed the live or dead status of the
      infected Ped-2E9 cells in gel matrix. This paper presents the first example of a
      cell-based sensing system using collagen-encapsulated mammalian cells for rapid
      detection of pathogenic bacteria or toxin, and demonstrates a potential for
      onsite use as a portable detection system.

PMID- 18059365
TI  - Functional and molecular interactions between the HGF/c-Met pathway and c-Myc in
      large-cell medulloblastoma.
AB  - The growth factor hepatocyte growth factor (HGF), also known as scatter factor,
      and its tyrosine kinase receptor c-Met play important roles in medulloblastoma
      malignancy. The transcription factor c-Myc is another contributor to the
      malignancy of these most common pediatric brain tumors. In the present study, we
      observed strong morphological similarities between medulloblastoma xenografts
      overexpressing HGF and medulloblastoma xenografts overexpressing c-Myc. We
      therefore hypothesized a biologically significant link between HGF/c-Met and c
      Myc in medulloblastoma malignancy and studied the molecular and functional
      interactions between them. We found that HGF induces c-Myc mRNA and protein in
      established and primary medulloblastoma cells. HGF regulated c-Myc levels via
      transcriptional and post-transcriptional mechanisms as evidenced by HGF induction
      of c-Myc promoter activity and induction of c-Myc protein levels in the setting
      of inhibited transcription and translation. We also found that HGF induces cell
      cycle progression, cell proliferation, apoptosis and increase in cell size in a c
      Myc-dependent manner. Activation of MAPK and PI3K, inhibition of GSK-3beta and
      translocation of beta-catenin to the nucleus as well as Tcf/Lef transcriptional
      activity were involved in mediating c-Myc induction by HGF. Induction of Cdk2
      kinase activity was involved in mediating the cell cycle progression effects, and
      downregulation of Bcl-XL was involved in mediating the proapoptotic effects of
      HGF downstream of c-Myc. All molecules that mediated the effects of HGF on c-Myc
      expression, cell proliferation and apoptosis were expressed in human large-cell
      medulloblastoma tissues. We therefore established for the first time a functional
      cooperation between HGF/c-Met and c-Myc in human medulloblastoma and elucidated
      the molecular mechanisms of this cooperation. The findings provide a potential
      explanation for the high frequency of c-Myc overexpression in medulloblastoma and
      suggest a cooperative role for c-Met and c-Myc in large-cell anaplastic
      medulloblastoma formation.

PMID- 18059366
TI  - Off the beaten pathway: the complex cross talk between Notch and NF-kappaB.
AB  - The canonical Notch pathway that has been well characterized over the past 25
      years is relatively simple compared to the plethora of recently published data
      suggesting non-canonical signaling mechanisms and cross talk with other pathways.
      The manner in which other pathways cross talk with Notch signaling appears to be
      extraordinarily complex and, not surprisingly, context-dependent. While the
      physiological relevance of many of these interactions remains to be established,
      there is little doubt that Notch signaling is integrated with numerous other
      pathways in ways that appear increasingly complex. Among the most intricate cross
      talks described for Notch is its interaction with the NF-kappaB pathway, another
      major cell fate regulatory network involved in development, immunity, and cancer.
      Numerous reports over the last 11 years have described multiple cross talk
      mechanisms between Notch and NF-kappaB in diverse experimental models. This
      article will provide a brief overview of the published evidence for Notch-NF
      kappaB cross talk, focusing on vertebrate systems.

PMID- 18059367
TI  - Is evolvability evolvable?
AB  - In recent years, biologists have increasingly been asking whether the ability to
      evolve--the evolvability--of biological systems, itself evolves, and whether this
      phenomenon is the result of natural selection or a by-product of other
      evolutionary processes. The concept of evolvability, and the increasing
      theoretical and empirical literature that refers to it, may constitute one of
      several pillars on which an extended evolutionary synthesis will take shape
      during the next few years, although much work remains to be done on how
      evolvability comes about.

PMID- 18059368
TI  - Nucleosome destabilization in the epigenetic regulation of gene expression.
AB  - Assembly, mobilization and disassembly of nucleosomes can influence the
      regulation of gene expression and other processes that act on eukaryotic DNA.
      Distinct nucleosome-assembly pathways deposit dimeric subunits behind the
      replication fork or at sites of active processes that mobilize pre-existing
      nucleosomes. Replication-coupled nucleosome assembly appears to be the default
      process that maintains silent chromatin, counteracted by active processes that
      destabilize nucleosomes. Nucleosome stability is regulated by the combined
      effects of nucleosome-positioning sequences, histone chaperones, ATP-dependent
      nucleosome remodellers, post-translational modifications and histone variants.
      Recent studies suggest that histone turnover helps to maintain continuous access
      to sequence-specific DNA-binding proteins that regulate epigenetic inheritance,
      providing a dynamic alternative to histone-marking models for the propagation of
      active chromatin.

PMID- 18059369
TI  - Cell surface nucleolin serves as receptor for DNA nanoparticles composed of
      pegylated polylysine and DNA.
AB  - Compacted DNA nanoparticles deliver transgenes efficiently to the lung following
      intrapulmonary dosing. Here we show that nucleolin, a protein known to shuttle
      between the nucleus, cytoplasm, and cell surface, is a receptor for DNA
      nanoparticles at the cell surface. By using surface plasmon resonance (SPR), we
      demonstrate that nucleolin binds to DNA nanoparticles directly. The presence of
      nucleolin on the surface of HeLa and 16HBEo- cells was confirmed by surface
      biotinylation assay and immunofluorescence. Rhodamine-labeled DNA nanoparticles
      colocalize with nucleolin on the cell surface, as well as in the cytoplasm and
      nucleus, but not with transferrin or markers of early endosome or lysosome
      following cellular uptake. Reducing nucleolin on the cell surface by serum-free
      medium or siRNA against nucleolin treatment leads to significant reduction in
      luciferase reporter gene activity, while overexpressing nucleolin has the
      opposite effect. Competition for binding to DNA nanoparticles with exogenous
      purified nucleolin decreases the transfection efficiency by 60-90% in a dose
      dependent manner. Therefore, the data strongly suggest that cell surface
      nucleolin serves as a receptor for DNA nanoparticles, and that nucleolin is
      essential for internalization and/or transport of the nanoparticles from cell
      surface to the nucleus.

PMID- 18059370
TI  - Induction of natural killer cell-dependent antitumor immunity by the Autographa
      californica multiple nuclear polyhedrosis virus.
AB  - Wild-type Autographa californica multiple nuclear polyhedrosis virus (AcMNPV)
      infects a variety of mammalian cell types in vitro, but does not replicate in
      these cells. We investigated the effects of AcMNPV in the induction of the immune
      response and tumor metastasis in mice. After intravenous injection, AcMNPV was
      taken up by the liver and spleen, and preferentially infected dendritic cells
      (DCs) and B cells in the spleen; costimulatory molecules CD40, CD80, and CD86
      were upregulated in the DCs. The hepatic mononuclear cells (MNCs) in these
      animals were highly cytotoxic to natural killer (NK)-sensitive YAC-1 and B16
      melanoma cells, but not to NK-resistant EL4 cells. Intravenous injection of
      AcMNPV-induced NK cell proliferation in the liver and spleen, and enhanced
      antitumor immunity in mice with B16 liver metastases. Furthermore, such treatment
      increased the survival of C57BL/6, J alpha 281 (-/-), and interferon (IFN)-gamma
      (-/-) mice that were previously injected with B16 tumor cells. AcMNPV injection
      did not enhance the survival of NK cell-depleted mice. Moreover, one AcMNPV
      treatment effectively prolonged survival in a B16 liver metastasis model, and was
      equivalent to five treatments with recombinant interleukin-12 (IL-12) protein.
      These findings suggest that AcMNPV efficiently stimulates NK cell-mediated
      antitumor immunity.

PMID- 18059371
TI  - Input DNA ratio determines copy number of the 33 kb Factor IX gene on de novo
      human artificial chromosomes.
AB  - Human artificial chromosomes (ACs) are non-integrating vectors that may be useful
      for gene therapy. They assemble in cultured cells following transfection of human
      centromeric alpha -satellite DNA and segregate efficiently alongside the host
      genome. In the present study, a 33 kilobase (kb) Factor IX (FIX) gene was
      incorporated into mitotically stable ACs in human HT1080 lung derived cells using
      co-transfection of a bacterial artificial chromosome (BAC) harboring synthetic
      alpha -satellite DNA and a P1 artificial chromosome(PAC) that spans the FIX
      locus. ACs were detected in >or=90% of chromosome spreads in 8 of 19 lines
      expanded from drug resistant colonies. FIX transgene copy number on ACs was
      determined by input DNA transfection ratios. Furthermore, a low level of FIX
      transcription was detected from ACs with multiple transgenes but not from those
      incorporating a single transgene, suggesting that reducing transgene number may
      limit misexpression. Their potential to segregate cross species was measured by
      transferring ACs into mouse and hamster cell lines using microcell-mediated
      chromosome transfer. Lines were obtained where ACs segregated efficiently. The
      stable segregation of ACs in rodent cells suggests that it should be possible to
      develop animal models to test the capacity of ACs to rescue FIX deficiency.

PMID- 18059372
TI  - Downregulation of monocyte chemoattractant protein-1 involving short interfering
      RNA attenuates hapten-induced contact hypersensitivity.
AB  - Contact hypersensitivity (CHS) is a common skin disease, presenting clinically as
      allergic contact dermatitis. At inflammatory sites in a typical CHS model in the
      mouse ear, elevated expression of monocyte chemoattractant protein-1 (MCP-1) has
      been reported. MCP-1 is a potent chemotactic factor for many types of leukocytes
      including monocytes/macrophages and T cells. In this study, we aimed at
      developing a therapy for CHS involving RNA interference targeting MCP-1. A short
      interfering RNA (siRNA) to mouse MCP-1 successfully inhibited the secretion of
      MCP-1 by a fibroblastic cell line, L929, and RAW 264.7 cells derived from
      macrophages, and strikingly suppressed ear swelling in a CHS model. The siRNA
      systemically administered inhibited the infiltration of both
      monocytes/macrophages and T cells in the CHS model. Atelocollagen was used in
      this therapy as a delivery reagent for siRNA into the animal body. Atelocollagen
      facilitated the incorporation of the siRNA into macrophages/monocytes and
      fibroblasts, which vigorously secrete MCP-1 protein at inflammatory sites in CHS.
      This therapy had no adverse effects such as induction of interferon, or liver or
      renal damage. Our data indicate that the systemic delivery of siRNA targeting MCP
      1 is a potent therapeutic strategy for CHS treatment.

PMID- 18059373
TI  - Optimization of self-complementary AAV vectors for liver-directed expression
      results in sustained correction of hemophilia B at low vector dose.
AB  - Self-complementary adeno-associated virus (scAAV) vectors can significantly
      minimize the vector load required to achieve sustained transgene expression. In
      this study, transcriptional regulatory elements were systematically screened to
      produce constitutive and liver-specific scAAV factor IX (FIX) expression
      cassettes. In addition, optimization of GC content, cis- regulatory elements, and
      codon usage in the human FIX (hFIX) transgene increased expression 4-20-fold. A
      vector was developed that was capable of expressing high FIX levels in comparison
      with the single-stranded (ss) AAV vector used in a recent clinical trial. The
      ssAAV and scAAV vectors display different transgene expression and genome
      stability patterns in the liver, as determined by immunohistochemical staining,
      in situ messenger RNA (mRNA) hybridization and vector genome quantitation. The
      ssAAV2 vector promoted strong FIX expression in only a subset of hepatocytes. The
      scAAV2-hFIX vector showed widespread ( approximately 80% of hepatocytes),
      moderate FIX expression levels similar to normal livers with correction of
      coagulation function in FIX-deficient mice. The ability of low dose scAAV-FIX
      vectors to achieve near-physiological expression may circumvent inflammatory
      responses in the liver. In addition to providing an improved scAAV vector for
      potential application in future hemophilia B clinical trials and liver-directed
      gene delivery, these studies underscore the need for rigorous analysis and
      optimization of vector genome cassettes.

PMID- 18059374
TI  - Enhanced antitumor immunity elicited by dendritic cell vaccines is a result of
      their ability to engage both CTL and IFN gamma-producing NK cells.
AB  - Activation of cytotoxic T lymphocytes (CTLs) is a primary goal of many cancer
      vaccination therapies. We have evaluated two vaccination platforms, dendritic
      cells (DCs) and recombinant adenoviruses (rAds), for their ability to elicit CTL
      response and antitumor protection. Although rAd was more potent in CTL priming,
      DC vaccination provided greater protective and therapeutic antitumor activity.
      Subsequent analyses ruled out the possibility that the two vaccines elicit
      qualitatively distinct CTL, and demonstrated instead that DCs could better engage
      natural killer (NK) cells as an additional effector mechanism. We demonstrated
      that, although both DCs and rAd can stimulate rapid NK expansion, only DC
      activated NK cells are able to produce interferon-gamma (IFN gamma) and mediate
      antitumor protection. Moreover, our data showed that exogenously delivered DCs
      preferentially engaged the Mac-1(high)CD27(high) NK subset, thereby suggesting
      that this NK population plays a predominant role in NK:DC interaction.
      Interestingly, at least 3 days were required for DC-triggered NK cells to acquire
      effector functions, indicating that a similar priming process operates between T
      cells and NK cells. Our results suggest that the nature of the vaccine platform
      can determine the relative involvement of NK and T cells in antitumor immunity,
      and that methods to augment NK function should be included in vaccination
      strategies in order to complement CTL-mediated control of tumor growth.

PMID- 18059376
TI  - Is total thyroidectomy the procedure of choice for low-risk papillary thyroid
      cancer?

PMID- 18059375
TI  - Rapid/sustained anti-anthrax passive immunity mediated by co-administration of
      Ad/AAV.
AB  - Achieving both immediate and sustained protection against diseases caused by
      bacterial toxins and extracellular pathogens is a challenge in developing
      biodefense therapeutics. We hypothesized that a single co-administration of an
      adenovirus (Ad) vector and an adeno-associated virus (AAV) vector, both
      expressing a pathogen-specific monoclonal antibody, would provide rapid,
      persistent passive immunotherapy against the pathogen. In order to test this
      strategy, we used the lethal toxin of Bacillus anthracis as a target of a
      monoclonal antibody directed against the protective antigen (PA) component of the
      toxin, using co-administration of an Ad vector encoding an anti-PA monoclonal
      antibody (AdalphaPA) and an AAV vector encoding an anti-PA monoclonal antibody
      (AAVrh.10alphaPA). As early as 1 day after co-administration of AdalphaPA and
      AAVrh.10alphaPA to mice, serum anti-PA antibody levels were detectable, and were
      sustained through 6 months. Importantly, animals that received both vectors were
      protected against toxin challenge as early as 1 day after administration and
      throughout the 6 month duration of the experiment. These data provide a new
      paradigm of genetic passive immunotherapy by co-administration of Ad and AAV
      vectors, each encoding a pathogen-specific monoclonal antibody, as an effective
      approach for both rapid and sustained protection against a bio-terror attack.

PMID- 18059377
TI  - Is hypopituitarism predictable after traumatic brain injury?

PMID- 18059378
TI  - Involvement of sphingoid bases in mediating reactive oxygen intermediate
      production and programmed cell death in Arabidopsis.
AB  - Sphingolipids have been suggested to act as second messengers for an array of
      cellular signaling activities in plant cells, including stress responses and
      programmed cell death (PCD). However, the mechanisms underpinning these processes
      are not well understood. Here, we report that an Arabidopsis mutant, fumonisin B1
      resistant 11-1 (fbr 11-1), which fails to generate reactive oxygen intermediates
      (ROIs), is incapable of initiating PCD when the mutant is challenged by fumonisin
      B(1) (FB(1)), a specific inhibitor of ceramide synthase. Molecular analysis
      indicated that FBR11 encodes a long-chain base 1 (LCB1) subunit of serine
      palmitoyltransferase (SPT), which catalyzes the first rate-limiting step of de
      novo sphingolipid synthesis. Mass spectrometric analysis of the sphingolipid
      concentrations revealed that whereas the fbr 11-1 mutation did not affect basal
      levels of sphingoid bases, the mutant showed attenuated formation of sphingoid
      bases in response to FB(1). By a direct feeding experiment, we show that the free
      sphingoid bases dihydrosphingosine, phytosphingosine and sphingosine efficiently
      induce ROI generation followed by cell death. Conversely, ROI generation and cell
      death induced by dihydrosphingosine were specifically blocked by its
      phosphorylated form dihydrosphingosine-1-phosphate in a dose-dependent manner,
      suggesting that the maintenance of homeostasis between a free sphingoid base and
      its phosphorylated derivative is critical to determining the cell fate. Because
      alterations of the sphingolipid level occur prior to the ROI production, we
      propose that the free sphingoid bases are involved in the control of PCD in
      Arabidopsis, presumably through the regulation of the ROI level upon receiving
      different developmental or environmental cues.

PMID- 18059379
TI  - Is LDLT appropriate for patients with chronic HCV infection?

PMID- 18059380
TI  - Is cornstarch-thickened milk formula better than strengthened regular milk
      formula for infant regurgitation?

PMID- 18059381
TI  - Screening for familial hypercholesterolemia: what is the most effective strategy?

PMID- 18059382
TI  - Is pediatric hypertension underdiagnosed?

PMID- 18059383
TI  - Pay for performance in myocardial infarction: are we reaping the rewards?

PMID- 18059384
TI  - Is statin discontinuation an option in patients who have had a stroke?

PMID- 18059385
TI  - Anticoagulants for intracranial artery dissection without subarachnoid hemorrhage
      -safe but not sound?

PMID- 18059386
TI  - Does frequent nocturnal hemodialysis result in better outcomes than conventional
      thrice-weekly hemodialysis?

PMID- 18059387
TI  - Prophylactic hemodialysis for the prevention of contrast-induced nephropathy
      after coronary angiography.

PMID- 18059388
TI  - Why rheumatologists should be involved in the treatment of lupus nephritis.

PMID- 18059389
TI  - Is the risk of serious infections increased in patients with RA who receive
      treatment with antirheumatic drugs?

PMID- 18059390
TI  - Which pathological features of renal cell carcinoma have the greatest prognostic
      value?

PMID- 18059391
TI  - Oral versus parenteral antibiotics for the initial treatment of a first episode
      of acute pyelonephritis in children.

PMID- 18059392
TI  - Screening for breast cancer: is it globally applicable?

PMID- 18059393
TI  - Antibiotic use and risk of non-Hodgkin's lymphoma: a population-based case
      control study.
AB  - Antibiotic use in 759 non-Hodgkin's lymphoma (NHL) patients and 589 controls was
      compared. Neither total antibiotic use (odds ratio=0.7, 95% confidence
      interval=0.5-1.2), nor antibiotic use by site, was associated with total NHL, or
      NHL subtypes. There were no trends with frequency or age at first use (P
      trend=0.23 and 0.26, respectively).

PMID- 18059394
TI  - Hodgkin's disease and birth outcome: a Danish nationwide cohort study.
AB  - In a Danish nationwide cohort study of 292 births from 1973 to 2002 in women with
      Hodgkin's disease (HD), we compared birth outcome with 14 042 births from a
      cohort of mothers without cancer. We found no substantially increased risk of
      preterm birth, low birth weight at term, or stillbirth and no difference in
      proportion of male newborns for 192 children of women with HD before pregnancy.
      The prevalence odds ratio (POR) for congenital abnormalities was 1.7 (95%
      confidence interval (CI): 0.9-3.1). Among 15 newborns of mothers diagnosed during
      pregnancy, the POR of preterm birth was 26.6 (95% CI: 8.5-83.0), but five out of
      the eight preterm deliveries among these women were elective. We found no
      substantially increased risk of adverse birth outcome among 85 newborns of women
      diagnosed within 2 years postpartum, though effect estimates were imprecise. The
      overall findings are reassuring, they cannot exclude the possibility of an
      increased risk of congenital abnormalities for newborns of women diagnosed with
      HD before pregnancy.

PMID- 18059395
TI  - A mathematical modelling tool for predicting survival of individual patients
      following resection of glioblastoma: a proof of principle.
AB  - The prediction of the outcome of individual patients with glioblastoma would be
      of great significance for monitoring responses to therapy. We hypothesise that,
      although a large number of genetic-metabolic abnormalities occur upstream, there
      are two 'final common pathways' dominating glioblastoma growth - net rates of
      proliferation (rho) and dispersal (D). These rates can be estimated from features
      of pretreatment MR images and can be applied in a mathematical model to predict
      tumour growth, impact of extent of tumour resection and patient survival. Only
      the pre-operative gadolinium-enhanced T1-weighted (T1-Gd) and T2-weighted (T2)
      volume data from 70 patients with previously untreated glioblastoma were used to
      derive a ratio D/rho for each patient. We developed a 'virtual control' for each
      patient with the same size tumour at the time of diagnosis, the same ratio of net
      invasion to proliferation (D/rho) and the same extent of resection. The median
      durations of survival and the shapes of the survival curves of actual and
      'virtual' patients subjected to biopsy or subtotal resection (STR) superimpose
      exactly. For those actually receiving gross total resection (GTR), as shown by
      post-operative CT, the actual survival curve lies between the 'virtual' results
      predicted for 100 and 125% resection of the T1-Gd volume. The concordance between
      predicted (virtual) and actual survivals suggests that the mathematical model is
      realistic enough to allow precise definition of the effectiveness of
      individualised treatments and their site(s) of action on proliferation (rho)
      and/or dispersal (D) of the tumour cells without knowledge of any other clinical
      or pathological information.

PMID- 18059396
TI  - A case-control study of the impact of the East Anglian breast screening programme
      on breast cancer mortality.
AB  - Although breast cancer screening has been shown to work in randomised trials,
      there is a need to evaluate service screening programmes to ensure that they are
      delivering the benefit indicated by the trials. We carried out a case-control
      study to investigate the effect of mammography service screening, in the NHS
      breast screening programme, on breast cancer mortality in the East Anglian region
      of the UK. Cases were deaths from breast cancer in women diagnosed between the
      ages of 50 and 70 years, following the instigation of the East Anglia Breast
      Screening Programme in 1989. The controls were women (two per case) who had not
      died of breast cancer, from the same area, matched by date of birth to the cases.
      Each control was known to be alive at the time of death of her matched case. All
      women were known to the breast screening programme and were invited, at least
      once, to be screened. There were 284 cases and 568 controls. The odds ratio (OR)
      for risk of death from breast cancer in women who attended at least one routine
      screen compared to those who did not attend was 0.35 (CI: 0.24, 0.50). Adjusting
      for self-selection bias gave an estimate of the breast cancer mortality reduction
      associated with invitation to screening of 35% (OR=0.65, 95% CI: 0.48, 0.88). The
      effect of actually being screened was a 48% breast cancer mortality reduction
      (OR=0.52, 95% CI: 0.32, 0.84). The results suggest that the National Breast
      Screening Programme in East Anglia is achieving a reduction in breast cancer
      deaths, which is at least consistent with the results from the randomised
      controlled trials of mammographic screening.

PMID- 18059398
TI  - How do patients want to learn of results of clinical trials? A survey of 1431
      breast cancer patients.
AB  - Questionnaires were circulated to UK patients and health care professionals
      (HCPs) participating in the Taxotere as Adjuvant ChemoTherapy (TACT) trial in
      autumn 2004 asking if and how trial results, when available, should be conveyed
      to patients. A total of 1431 (37% of surviving UK TACT patients) returned
      questionnaires. In all, 30 (2%) patients did not want results. In all, 554 (40%)
      patients preferred to receive them via their hospital; 664 (47%) preferred
      results posted directly to their home, 177 (13%) preferred a letter providing a
      telephone number to request results. Six hundred and twelve patients thought
      results should come directly from the trials office. One hundred and seventy-six
      HCPs from 89 UK centres (86%) returned questionnaires. In all, 169 out of 176
      patients (96%) thought results should be written in lay terms for patients.
      Seventy (41%) preferred patients to receive results via their hospital; 64 (38%)
      preferred a letter providing a telephone number to request results, and 32 (19%)
      preferred results posted directly to patients. Thirty-one HCPs (18%) thought
      results to patients should come directly from the trials office. A total of 868
      (61%) patients thought next of kin of deceased patients should receive results,
      543 (38%) did not; 47 (27%) HCPs thought they should; 118 (68%) did not.

PMID- 18059397
TI  - A combination of gefitinib and FOLFOX-4 as first-line treatment in advanced
      colorectal cancer patients. A GISCAD multicentre phase II study including a
      biological analysis of EGFR overexpression, amplification and NF-kB activation.
AB  - Interesting activity has been reported by combining chemotherapy with cetuximab.
      An alternative approach for blocking EGFR function has been the development of
      small-molecule inhibitors of tyrosine kinase domain such as gefitinib. We
      designed a multicentre phase II study in advanced colorectal cancer combining
      gefitinib+FOLFOX in order to determine the activity and to relate EGFR expression
      and gene amplification and NF-kB activation to therapeutic results. Patients
      received FOLFOX-4 regimen plus gefitinib as first-line treatment. Tumour samples
      were analysed for EGFR protein expression by immunohistochemical analysis and for
      EGFR gene amplification by fluorescence in situ hybridisation (FISH), chromogenic
      in situ hybridisation (CISH) and NF-kB activation. Forty-three patients were
      enrolled into this study; 15 patients experienced a partial response (response
      rate=34.9%), whereas other 12 (27.9%) had a stable disease. Median progression
      free survival (PFS) was 7.8 months and median overall survival (OS) was 13.9
      months. We did not find any relationship with EGFR overexpression, gene
      amplification, while NF-kB activation was associated with a resistance to
      therapy. Gefitinib does not seem to increase the activity of FOLFOX in advanced
      colorectal cancer even in patients overexpressing EGFR or with EGFR
      amplification. Furthermore, while NF-kB activation seems to predict resistance to
      chemotherapy as demonstrated 'in vitro' models, gefitinib does not overcome this
      mechanism of resistance, as reported for cetuximab.

PMID- 18059399
TI  - Dietary iron and haem iron intake and risk of endometrial cancer: a prospective
      cohort study.
AB  - We used data from a large cohort study of Canadian women to assess the
      association of meat intake and dietary intake of iron and haem iron with risk of
      endometrial cancer. Among 34,148 women with an intact uterus at baseline and
      followed for a mean of 16.4 years, we identified 426 incident endometrial cancer
      cases. Data from a food frequency questionnaire administered at baseline were
      used to calculate intake of all meats, red meat, total dietary iron, iron from
      meat, haem iron, and non-haem iron. Analyses were carried out using Cox
      proportional hazards models with adjustment for known risk factors and
      covariates. We found no association of intake of meat or any of the dietary iron
      related variables with risk of endometrial cancer.

PMID- 18059400
TI  - Downregulation of drug transport and metabolism in mice bearing extra-hepatic
      malignancies.
AB  - There is increasing evidence of a systemic inflammatory response associated with
      malignancy, which may have an impact on both drug disposition and resistance to
      cytotoxic therapy. The impact of inflammation on drug disposition was studied in
      mice bearing a number of common tumour xenografts. C57BL/6 mice were inoculated
      with tumour xenografts. Hepatic expressions of Cyp3a and drug transporters were
      analysed at the mRNA, protein and functional levels (Cyp3a only). Circulating
      serum cytokines and the hepatic expression of acute phase proteins (APPs) were
      measured. Intratumoral levels of multidrug resistance genes were determined.
      Tumour xenografts elicited an inflammatory response that coincided with
      repression in hepatic Cyp3a11 activity and the expression of a number of hepatic
      drug transporters. With tumour growth, a progressive reduction in hepatic Cyp3a11
      mRNA expression was seen. Conversely, an increase in the hepatic APP expression
      and circulating interleukin (IL)-6 levels was observed. Furthermore, a
      correlation was seen between increased intratumoral expression of the multidrug
      resistance gene, Mdr1a, and levels of circulating IL-6. Malignancy results in
      reduced hepatic drug disposition that correlates with an associated inflammatory
      response. Reduction of inflammation may improve the clinical outcome for patients
      receiving chemotherapeutic agents that undergo hepatic metabolism.

PMID- 18059402
TI  - Genomic copy number and expression patterns in testicular germ cell tumours.
AB  - Testicular germ cell tumours of adults and adolescents (TGCT) include seminomas
      (SE) and nonseminomas (NS), with spermatocytic seminomas (SSE) representing a
      distinct entity in older men. SE and NS have gain of 12p material in all cases,
      whereas SSE are associated with overrepresentation of chromosome 9. Here, we
      compare at the chromosomal level, copy number imbalances with global expression
      changes, identified by comparative expressed sequence hybridisation analyses, in
      seven SE, one combined tumour, seven NS and seven cell lines. Positive
      correlations were found consistent with copy number as a main driver of
      expression change, despite reported differences in methylation status in SE and
      NS. Analysis of chromosomal copy number and expression data could not distinguish
      between SE and NS, in-keeping with a similar genetic pathogenesis. However,
      increased expression from 4q22, 5q23.2 and 9p21 distinguished SSE from SE and NS
      and decreased copy number and expression from 2q36-q37 and 6q24 was a specific
      feature of NS-derived cell lines. Our analysis also highlights 19 regions with
      both copy number and expression imbalances in greater than 40% of cases. Mining
      available expression array data identified genes from these regions as candidates
      for involvement in TGCT development. Supplementary data is available at
      http://www.crukdmf.icr.ac.uk/array/array.html.

PMID- 18059401
TI  - Influences on pre-hospital delay in the diagnosis of colorectal cancer: a
      systematic review.
AB  - Colorectal cancer is a major global health problem, with survival varying
      according to stage at diagnosis. Delayed diagnosis can result from patient,
      practitioner or hospital delay. This paper reports the results of a review of the
      factors influencing pre-hospital delay - the time between a patient first
      noticing a cancer symptom and presenting to primary care or between first
      presentation and referral to secondary care. A systematic methodology was
      applied, including extensive searches of the literature published from 1970 to
      2003, systematic data extraction, quality assessment and narrative data
      synthesis. Fifty-four studies were included. Patients' non-recognition of symptom
      seriousness increased delay, as did symptom denial. Patient delay was greater for
      rectal than colon cancers and the presence of more serious symptoms, such as
      pain, reduced delay. There appears to be no relationship between delay and
      patients' age, sex or socioeconomic status. Initial misdiagnosis, inadequate
      examination and inaccurate investigations increased practitioner delay. Use of
      referral guidelines may reduce delay, although evidence is currently limited. No
      intervention studies were identified. If delayed diagnosis is to be reduced,
      there must be increased recognition of the significance of symptoms among
      patients, and development and evaluation of interventions that are designed to
      ensure appropriate diagnosis and examination by practitioners.

PMID- 18059403
TI  - The interaction between impulsivity and a varied food environment: its influence
      on food intake and overweight.
AB  - OBJECTIVE: The current study tests the influence of two factors, the obesogenic
      environment and impulsivity, on food intake in primary school children. Our
      current food environment offers a large variety of cheap and easily available
      sweet and fatty foods. This obesogenic environment is believed to be a cause of
      the recent obesity epidemic. Impulsive people are generally less successful at
      inhibiting prepotent responses and they are reward sensitive. We investigate
      whether the interaction between an obesogenic environment and an impulsive person
      leads to overeating. DESIGN: A quasi-experimental 2 (reward sensitive versus not
      reward sensitive) by 2 (successful response inhibitors versus unsuccessful
      response inhibitors) by 2 (monotonous versus varied food environment) between
      subjects design with caloric intake during a taste test as the main dependent
      variable. The link between impulsivity and overweight was also examined.
      SUBJECTS: 78 healthy primary school children (age: 8-10 years). MEASUREMENTS: We
      measured two aspects of impulsivity: reward sensitivity and deficient response
      inhibition. Subsequently, one aspect of the obesogenic environment was
      manipulated; half of the participants received monotonous food during a bogus
      taste test whereas the other half tasted food that was varied in colour, form,
      taste and texture. RESULTS: As expected, reward sensitivity interacted with
      variety. In the monotony group there was no difference in food intake between the
      less and more reward-sensitive children (183 kcal+/-23 s.d. versus 180 kcal+/-21
      s.d.). However, in the variety group the more reward-sensitive children ingested
      significantly more calories than the less reward-sensitive children (237 kcal+/
      30 s.d. versus 141 kcal+/-19 s.d.). Reward sensitivity was not linked to
      overweight. Deficient response inhibition did not interact with variety, but it
      was linked to overweight. CONCLUSION: It is suggested that reward sensitivity
      could be a causal mechanism for overeating in an obesogenic environment whereas
      prepotent response inhibition may be a maintaining factor of the problem of
      overeating.

PMID- 18059404
TI  - Weight maintenance, behaviors and barriers among previous participants of a
      university-based weight control program.
AB  - OBJECTIVE: To examine weight loss maintenance among previous participants of a
      university-based behavioral weight management program and to compare behavioral
      strategies and perceived barriers between successful and unsuccessful
      maintainers. METHOD: Previous program participants (n=179) completed mailed
      surveys assessing current weight, weight control behaviors and perceived barriers
      to weight loss maintenance. RESULTS: At 14.1+/-10.8 months following completion
      of treatment, survey respondents were on average 12.6+/-12.6 kg, or 11.3+/-10.7%,
      below baseline weight; 76.5% of respondents had successfully maintained weight,
      defined as maintaining a weight loss of at least 5% below baseline. Compared to
      unsuccessful maintainers, successful maintainers reported practicing four dietary
      and three physical activity weight control strategies more often and experiencing
      five barriers to healthy eating and exercise less often. After accounting for
      time since treatment and maximum weight loss while in treatment, the strongest
      correlates of successful weight loss maintenance were frequent exercise and
      perceived difficulty of weight management. CONCLUSIONS: Clinically meaningful
      weight loss maintenance was achieved by the majority of participants. Findings
      support the literature indicating that physical activity is one of the strongest
      predictors of successful weight loss maintenance. Findings also suggest that
      strategies to reduce the level of perceived effort required for long-term weight
      control may improve maintenance outcomes.

PMID- 18059405
TI  - Structure-effect relation of C18 long-chain fatty acids in the reduction of body
      weight in rats.
AB  - OBJECTIVE: To investigate the relationship between chemical structure and
      physiological effect, the efficacy and the molecular mechanisms involved in the
      reduction of body weight by C18 fatty acids (stearic, elaidic, oleic, linoleic
      and 2-hydroxyoleic acids (2-OHOA)). DESIGN: Ad libitum fed, lean Wistar Kyoto
      rats treated orally with up to 600 mg kg(-1) of the fatty acids or vehicle every
      12 h for 7 days. Besides, starved rats and rats pairfed to the 2-OHOA-treated
      group served as additional controls under restricted feeding conditions.
      MEASUREMENTS: Body weight, food intake, weight of various fat depots, plasma
      leptin, hypothalamic neuropeptides, uncoupling proteins (UCP) in white (WAT) and
      brown adipose tissue (BAT) and phosphorylation level of cyclic AMP (cAMP)
      response element-binding protein (CREB) in WAT. RESULTS: Only treatment with
      oleic acid and 2-OHOA induced body weight loss (3.3 and 11.4%, respectively)
      through reduction of adipose fat mass. Food intake in these rats was lower,
      although hypothalamic neuropeptide and plasma leptin levels indicated a rise in
      orexigenic status. Rats pairfed to the 2-hydroxyoleic group only lost 6.3% body
      weight. UCP1 expression and phosphorylation of CREB was drastically increased in
      WAT, but not BAT of 2-OHOA-treated rats, whereas no UCP1 expression could be
      detected in WAT of rats treated with oleic acid. CONCLUSION: Both cis-configured
      monounsaturated C18 fatty acids (oleic acid and 2-OHOA) reduce body weight, but
      the introduction of a hydroxyl group in position 2 drastically increases loss of
      adipose tissue mass. The novel molecular mechanism unique to 2-hydroxyoleic, but
      not oleic acid, implies induction of UCP1 expression in WAT by the cAMP/PKA
      pathway-dependent transcription factor CREB, most probably as part of a
      transdifferentiation process accompanied by enhanced energy expenditure.

PMID- 18059407
TI  - Perinatal predictors of overweight at infancy and preschool childhood: the
      GENESIS study.
AB  - OBJECTIVE: To identify those perinatal parameters and characteristics
      predisposing children to an increased risk of overweight during infancy and
      preschool years. DESIGN: The analyses were performed using data from the Growth,
      Exercise and Nutrition Epidemiological Study In preSchoolers. SUBJECTS: A
      representative sample of 2374 Greek preschoolers 1-5 years old. MEASUREMENTS:
      Anthropometric data, such as body weight, recumbent length and standing height,
      were obtained by using standard procedures and measuring equipment. Structured
      interviews were conducted with both parents to collect information on
      anthropometric, demographic, medical and behavioral data. Finally, children's
      anthropometric data at birth, 6 and 12 months of age were recorded from their
      birth certificates and medical records. RESULTS: Children born large for
      gestational age were 4.59 and 2.19 times more likely for being overweight at 6
      and 12 months of age, respectively, than children born appropriate for
      gestational age. On the other hand, children that were exclusively breastfed were
      0.49 and 0.54 times less likely for being overweight at 6 and 12 months of age,
      respectively, than children that were exclusively formula fed. Furthermore, 3- to
      5-year-old children born to mothers who were both active and passive smokers
      during pregnancy were 1.79 times more likely of being overweight compared to
      children born to nonsmoking mothers. Finally, having an overweight father
      significantly increased the likelihood of childhood overweight at 12 months, 1-3
      and 3-5 years of age. CONCLUSION: Our findings showed that some of the perinatal
      parameters and characteristics examined in the current study predict overweight
      at infancy, while others at preschool years. Priority should be given to size at
      birth, breastfeeding, maternal smoking during pregnancy and parental overweight,
      when developing public health strategies to reduce the prevalence of childhood
      overweight and related chronic disease later in life.

PMID- 18059406
TI  - Stress-induced cytokine responses and central adiposity in young women.
AB  - BACKGROUND: Evidence suggests that people who are more responsive to
      psychological stress are at an increased risk of developing obesity. However, the
      biological mechanisms underlying this phenomenon are poorly understood. The
      cytokines leptin, interleukin-1 receptor antagonist (IL-1Ra) and interleukin-6
      (IL-6) play a key role in fat metabolism and abnormal circulating levels of these
      proteins have been reported in obese people and in individuals subject to stress.
      OBJECTIVE: This study investigated whether cytokine responses to acute mental
      stress are associated with adiposity in healthy young women. DESIGN AND SUBJECTS:
      A laboratory study of 67 women, aged 18-25 years, recruited from University
      College London. MEASUREMENTS: Height, weight and waist circumference were
      measured and body fat mass was estimated by bioelectrical impedance body
      composition analysis. Laboratory mental stress testing was carried out and blood
      pressure and heart rate were recorded at baseline, during two moderately
      challenging tasks (Stroop and speech) and during recovery 40-45 min post-stress.
      Blood samples taken at baseline, immediately post-stress and 45 min post-stress,
      were used for assessment of circulating cytokines. Saliva samples taken
      throughout the session were assessed for cortisol. RESULTS: Women who had larger
      cytokine responses to stress were more abdominally obese than women with smaller
      cytokine stress responses. Specifically, there was a positive correlation between
      waist circumference and stress-induced increases in plasma levels of leptin
      (r=0.35, P<0.05) and IL-1Ra responses (r=0.29, P<0.05). There was also a
      significant positive correlation between prolonged diastolic blood pressure
      responses to stress and measures of total and abdominal obesity (r=0.28-0.33,
      P<0.05). CONCLUSION: Increased cytokine production could be a mechanism linking
      stress and abdominal obesity.

PMID- 18059408
TI  - Lack of starvation-induced activation of AMP-activated protein kinase in the
      hypothalamus of the Lou/C rats resistant to obesity.
AB  - OBJECTIVE: The AMP-activated protein kinase (AMPK) is involved in the control of
      food intake by the hypothalamus. The aim of this work was to investigate if
      modification of hypothalamic AMPK regulation could be related to the spontaneous
      food restriction of Lou/C rats, a strain resistant to obesity exhibiting a 40%
      reduction in caloric intake compared with their lean Wistar counterparts. DESIGN:
      Three-month-old male Lou/C rats were compared with age-matched male Wistar rats
      in both fed ad libitum and 24-h food deprivation state. MEASUREMENTS AND RESULTS:
      We first confirmed that starvation activated both isoforms of AMPK catalytic
      alpha subunits and enhanced the phosphorylation state of its downstream targets
      acetyl-CoA carboxylase and elongation factor 2 in the hypothalamus of Wistar
      rats. These changes were not observed in the hypothalamus of Lou/C rats.
      Interestingly, the starvation-induced changes in hypothalamic mRNA levels of the
      main orexigenic and anorexigenic neuropeptides were also blunted in the Lou/C
      rats. Analysis of the concentrations of circulating substrates and hormones known
      to regulate hypothalamic AMPK indicated that the starvation-induced changes in
      ghrelin, adiponectin and leptin were not observed in Lou/C rats. Furthermore, an
      increased phosphorylation state of signal transducer and activator of
      transcription 3 (STAT3), which admittedly mediates leptin signaling, was
      evidenced in the hypothalamus of the starved Lou/C rats, as well as modifications
      of expression of the leptin-sensitive genes suppressor of cytokine signaling-3
      and stearoyl-coenzyme A desaturase 1. In addition, despite reduced leptin level
      in fed Lou/C rats, the phosphorylation state of hypothalamic STAT3 remained
      similar to that found in fed Wistar rats, an adaptation that could be explained
      by the concomitant increase in ObRb leptin receptor mRNA expression. CONCLUSION:
      Activation of hypothalamic AMPK by starvation, which stimulates food intake
      through changes in (an)orexigenic neuropeptides in the normal rats, was not
      observed in the spontaneously hypophagic Lou/C rats.

PMID- 18059411
TI  - Polysialic acid in the plasticity of the developing and adult vertebrate nervous
      system.
AB  - Polysialic acid (PSA) is a cell-surface glycan with an enormous hydrated volume
      that serves to modulate the distance between cells. This regulation has direct
      effects on several cellular mechanisms that underlie the formation of the
      vertebrate nervous system, most conspicuously in the migration and
      differentiation of progenitor cells and the growth and targeting of axons. PSA is
      also involved in a number of plasticity-related responses in the adult CNS,
      including changes in circadian and hormonal patterns, adaptations to pain and
      stress, and aspects of learning and memory. The ability of PSA to increase the
      plasticity of neural cells is being exploited to improve the repair of adult CNS
      tissue.

PMID- 18059412
TI  - Smc5/6: a link between DNA repair and unidirectional replication?
AB  - Of the three structural maintenance of chromosome (SMC) complexes, two directly
      regulate chromosome dynamics. The third, Smc5/6, functions mainly in homologous
      recombination and in completing DNA replication. The literature suggests that
      Smc5/6 coordinates DNA repair, in part through post-translational modification of
      uncharacterized target proteins that can dictate their subcellular localization,
      and that Smc5/6 also functions to establish DNA-damage-dependent cohesion. A
      nucleolar-specific Smc5/6 function has been proposed because Smc5/6 yeast mutants
      display penetrant phenotypes of ribosomal DNA (rDNA) instability. rDNA repeats
      are replicated unidirectionally. Here, we propose that unidirectional
      replication, combined with global Smc5/6 functions, can explain the apparent rDNA
      specificity.

PMID- 18059415
TI  - Diet quality and mortality: a population-based prospective study of men.
AB  - BACKGROUND/OBJECTIVES: To study quality of diet in relation to all-cause
      mortality, cardiovascular disease (CVD) and cancer mortality. SUBJECTS/METHODS:
      The population-based prospective Cohort of Swedish Men (COSM) included 40 837
      men, 45-79 years of age, who filled in a FFQ (96 food items) and were CVD- and
      cancer-free at baseline. Quality of diet was assessed by Recommended Food Score
      (RFS) based on 36 items and Non-Recommended Food Score (Non-RFS) based on 16
      items. Cox's proportional hazards regression models were used to estimate the
      hazard ratios (HRs) of mortality and 95% confidence intervals (CIs). Multivariate
      HRs for RFS and Non-RFS were adjusted for age, education, physical activity,
      martial status, self-perceived health status, smoking status, dietary supplements
      use, WHR, alcohol use, intake of energy and mutually adjusted. RESULTS: Between
      1998 and 2005, 4501 deaths from all-causes were registered. Between 1998 and
      2003, there were 1394 CVD and 759 cancer deaths. High RFS (> or =28) compared
      with low (< or =20) was associated with lower risk of all-cause mortality (HR:
      0.81; 95% CI: 0.71-0.91; P-value for trend<0.0001) and CVD mortality (HR: 0.71;
      95% CI: 0.54-0.93; P-value for trend=0.003). In contrast, men with high Non-RFS
      (> or =5) had higher risk of all-cause (HR: 1.21; 95% CI: 1.09-1.34; P-value for
      trend=0.001) and CVD mortality (HR: 1.27; 95% CI: 1.05-1.54; P-value for
      trend=0.07) compared to those with low Non-RFS (< or =2 items). No significant
      associations with cancer mortality were observed. CONCLUSIONS: Both measures of
      diet quality, RFS and Non-RFS, showed statistically significant associations with
      all-cause and CVD mortality (recommended foods inversely while nonrecommended
      foods positively), but not with cancer mortality.

PMID- 18059416
TI  - 'Junk food' diet and childhood behavioural problems: results from the ALSPAC
      cohort.
AB  - BACKGROUND/OBJECTIVES: To determine whether a 'junk food' diet at age 4(1/2) is
      associated with behavioural problems at age 7. SUBJECTS/METHODS: Data on
      approximately 4000 children participating in the Avon Longitudinal Study of
      Parents and Children, a birth cohort recruited in Avon, UK in 1991/92 were used.
      Behavioural problems were measured at age 7 using the Strengths and Difficulties
      Questionnaire (SDQ; maternal completion). Total difficulties and scores for the
      five sub-scales (hyperactivity, conduct and peer problems, emotional symptoms and
      pro-social behaviour) were calculated. Principal components analysis of dietary
      data (frequency of consumption of 57 foods/drinks) collected at age 4(1/2) by
      maternal report was used to generate a 'junk food' factor. Data on confounders
      were available from questionnaires. RESULTS: A one standard deviation increase in
      'junk food' intake at age 4(1/2) years was associated with increased
      hyperactivity at age 7 (odds ratio: 1.19; 95% confidence interval: 1.10, 1.29).
      This persisted after adjustment for confounders including intelligence quotient
      score (odds ratio: 1.13; 95% confidence interval: 1.01, 1.15). There was little
      evidence to support an association between 'junk food' intake and overall
      behavioural difficulties or other sub-scales of the SDQ. CONCLUSIONS: Children
      eating a diet high in 'junk food' in early childhood were more likely to be in
      the top 33% on the SDQ hyperactivity sub-scale at age 7. This may reflect a long
      term nutritional imbalance, or differences in parenting style. This finding
      requires replication before it can provide an avenue for intervention.

PMID- 18059417
TI  - Evaluation of urinary iodine excretion as a biomarker for intake of milk and
      dairy products in pregnant women in the Norwegian Mother and Child Cohort Study
      (MoBa).
AB  - BACKGROUND/OBJECTIVES: Milk and dairy products are the main sources of iodine in
      the Norwegian diet. This is due to a high consumption of milk and dairy products
      combined with a relatively high concentration of iodine in milk because of
      mandatory iodine fortification of cow fodder. The aim of the present study was to
      investigate the relation between 24-h urinary iodine excretion and estimated
      dietary intake, and to explore the use of 24-h urinary iodine excretion as a
      possible biomarker for the intake of milk and dairy products when assessing the
      validity of a new food frequency questionnaire for pregnant women participating
      the Norwegian Mother and Child Cohort Study (MoBa). SUBJECT/METHODS: 119 women
      participated in a validation study. Iodine was analyzed in 24-h urine. Dietary
      intakes were estimated by a food frequency questionnaire (FFQ) and a 4-day
      weighed food diary (FD). Using linear regression, predictors of urinary iodine
      excretion were identified. The triangular method was applied to calculate
      validity coefficients. RESULTS: Significant predictors of 24-h urinary iodine
      excretion were: intake of dairy products, iodine-containing supplements and
      intake of fruit/vegetables. Fish/seafood intake and time of the year influenced
      24-h urinary iodine excretion, although not significantly. The validity
      coefficients observed for total intake of dairy products were 0.65, 0.94 and 0.52
      for the FFQ, the FD and the 24-h urinary iodine excretion, respectively.
      CONCLUSIONS: The present study showed that 24-h urinary iodine excretion may be a
      useful biomarker for validating the intake of milk and dairy products in pregnant
      Norwegian women.

PMID- 18059418
TI  - Drosophila unleashed: the 12-genome update of the genetic power horse has been
      released.

PMID- 18059419
TI  - 'It is not in my world': an exploration of attitudes and influences associated
      with cystic fibrosis carrier screening.
AB  - Carrier screening for cystic fibrosis has been recommended for pregnant women and
      their partners, individuals and couples prior to conception, and for people with
      a family history. Many pilot programmes offering cystic fibrosis carrier
      screening, most commonly in the prenatal setting, have shown that uptake and
      acceptability are high. This article explores perspectives of the Victorian
      community regarding carrier screening for cystic fibrosis prior to offering
      screening. In particular whether or not such carrier screening should be offered,
      the best time for offering carrier screening, the information required for making
      a decision about carrier screening, and how this information can best be
      provided. A qualitative approach was taken to enable exploration of the views of
      stakeholders. Four focus groups and 32 interviews were conducted with a total of
      68 participants. Participants were in agreement that cystic fibrosis carrier
      screening should be made available to everyone. However, potential consumers
      viewed cystic fibrosis carrier screening as 'not in my world' and were unlikely
      to request such screening unless it was offered by a health professional, or they
      had a family history. The best time for carrier screening was seen to be an
      individual preference and an information brochure was perceived to be useful when
      considering carrier screening. Lack of knowledge around the irrelevance of family
      history is a barrier to cystic fibrosis carrier screening. This study highlights
      the importance of community consultation, with stakeholders, prior to
      implementation of carrier screening programmes.

PMID- 18059420
TI  - Polymorphisms in the cardiac sodium channel promoter displaying variant in vitro
      expression activity.
AB  - Variable transcription of the cardiac sodium channel gene is a candidate
      mechanism determining arrhythmia susceptibility. We have previously cloned and
      characterized the core promoter and flanking region of SCN5A, encoding the
      cardiac sodium channel. Loss-of-function mutations in this gene have been
      reported in approximately 20% of patients with Brugada syndrome, an inherited
      cardiac electrical disorder associated with a high incidence of life-threatening
      arrhythmias. In this study, we identified DNA variants in the proximal 2.8 kb
      promoter region of SCN5A and determined their frequency in 1,121 subjects. This
      population consisted of 88 Brugada syndrome patients with no SCN5A coding region
      mutation, and 1,033 anonymized subjects from various ethnicities. Variant
      promoter activity was assayed in CHO cells and neonatal cardiomyocytes by
      transient transfection of promoter-reporter constructs. Single-nucleotide
      polymorphisms (SNPs) were identified at approximately 1/200 base pairs which are:
      11 in the 5'-flanking region, 1 in exon 1, and 5 in intron 1. In addition, a
      haplotype consisting of two SNPs in complete linkage disequilibrium was
      identified. Minor allele frequencies were >5% in at least one ethnic panel at
      5/19 polymorphic sites. In vitro functional analysis in cardiomyocytes identified
      four variants with significantly (P<0.05) reduced reporter activity (up to 63%
      reduction). The largest changes were seen with c.-225-1790 G>A, which reduced
      reporter activity by 62.8% in CHO cells and 55% in cardiomyocytes. From these
      results, we can conclude that the SCN5A core promoter includes multiple DNA
      polymorphisms with altered in vitro activity, further supporting the concept of
      interindividual variability in transcription of this cardiac ion channel gene.

PMID- 18059421
TI  - Infiltration of forest fire and residential wood smoke: an evaluation of air
      cleaner effectiveness.
AB  - Communities impacted by fine-particle air pollution (particles with an
      aerodynamic diameter less than 2.5 microm; PM(2.5)) from forest fires and
      residential wood burning require effective, evidence-based exposure-reduction
      strategies. Public health recommendations during smoke episodes typically include
      advising community members to remain indoors and the use of air cleaners, yet
      little information is available on the effectiveness of these measures. Our study
      attempted to address the following objectives: to measure indoor infiltration
      factor (F(inf)) of PM(2.5) from forest fires/wood smoke, to determine the
      effectiveness of high-efficiency particulate air (HEPA) filter air cleaners in
      reducing indoor PM(2.5), and to analyze the home determinants of F(inf) and air
      cleaner effectiveness (ACE). We collected indoor/outdoor 1-min PM(2.5) averages
      and 48-h outdoor PM(2.5) filter samples for 21 winter and 17 summer homes
      impacted by wood burning and forest fire smoke, respectively, during 2004-2005. A
      portable HEPA filter air cleaner was operated indoors with the filter removed for
      one of two sampling days. Particle F(inf) and ACE were calculated for each home
      using a recursive model. We found mean F(inf)+/-SD was 0.27+/-0.18 and 0.61+/
      0.27 in winter (n=19) and summer (n=13), respectively, for days when HEPA filters
      were not used. Lower F(inf)+/-SD values of 0.10+/-0.08 and 0.19+/-0.20 were found
      on corresponding days when HEPA filters were in place. Mean+/-SD ACE ([F(inf)
      without filter-F(inf) with filter]/F(inf) without filter) in winter and summer
      were 55+/-38% and 65+/-35%, respectively. Number of windows and season predicted
      F(inf) (P<0.001). No significant predictors of ACE were identified. Our findings
      show that remaining indoors combined with use of air cleaner can effectively
      reduce PM(2.5) exposure during forest fires and residential wood burning.

PMID- 18059422
TI  - 1-Hydroxypyrene concentrations in first morning voids and 24-h composite urine:
      intra- and inter-individual comparisons.
AB  - Urinary 1-hydroxypyrene (1-OHP) has been suggested as an exposure biomarker for
      polycyclic aromatic hydrocarbons (PAHs). However, it remains unknown whether a
      first morning urine sample can be used to reflect average exposure. In this
      paper, we examine intra-individual differences and inter-individual associations
      between first morning voids and 24-h composite urine samples. The analysis was
      performed using data collected from 100 adults who had a wide range of PAH
      exposure due to differences in their occupation, e.g., coke oven workers vs. non
      coke oven workers. For each subject, all the urine voids within each of two 24-h
      measurement periods were collected. Results showed a significant (40% to 62%)
      intra-individual difference between first morning voids and 24-h urinary 1-OHP
      concentrations (in ng/ml urine). Creatinine adjustments of 1-OHP concentrations
      (in micromol/mol urinary creatinine) reduced the intra-individual difference by
      approximately 10%. Across all the subjects, a high overall correlation (r=0.76)
      was observed between first morning and 24-h average 1-OHP concentrations. Work
      environment and sampling season were found to significantly affect the
      relationship between first morning and 24-h 1-OHP concentrations. An increase of
      1 ng/ml of first morning urinary 1-OHP predicted an increase of 0.5 and 0.25
      ng/ml of 24-h urinary 1-OHP for coke oven workers and non-coke oven workers,
      respectively. Data collected in a winter season showed a higher correlation
      between first morning and 24-h concentrations than data collected in a fall
      season. Creatinine adjustments did not significantly improve overall correlations
      between first morning void and 24-h measurements, but increased total variances
      for 24-h urines explained by first morning urines in coke workers.

PMID- 18059423
TI  - Allergen levels in inner city homes: baseline concentrations and evaluation of
      intervention effectiveness.
AB  - Allergens in house dust are risk factors for asthma causation and exacerbation,
      and asthma interventions often focus on exposure reduction using methods that may
      not be sustainable over time in low-income communities. A randomized controlled
      trial with up to six home visits was used to evaluate the effectiveness of two
      interventions focused on reducing dust loading and allergen concentrations in 47
      low-income inner-city households in Minneapolis, MN. The interventions, which
      included education and relatively inexpensive cleaning procedures, were developed
      using a community-based participatory consultation process with focus groups held
      in English, Somali, and Spanish to incorporate community feedback from
      participants into protocols and study design decisions. Change in levels of cat,
      cockroach, dust mite, and culturable fungi as well as overall dust loading were
      evaluated by measuring the difference in concentrations before and after the
      cleaning intervention, and mixed models were used to assess the effect of
      education and cleaning on baseline allergen levels during the final three home
      visits. The cleaning intervention significantly lowered dust loading in all
      households and culturable fungi levels in single family homes, reduced cat
      allergen concentrations in homes with cats, but had no significant effect on
      cockroach allergen levels. The cleaning intervention also modestly decreased the
      frequency of observed allergen concentrations above suggested health benchmarks
      for cat, cockroach, and fungi. The cleaning and education interventions had
      similar effects on baseline allergen levels measured during subsequent home
      visits; both interventions significantly reduced baseline levels of cat and
      fungal allergens observed in pre-cleaning samples, but had no significant effect
      on cockroach allergen levels. Overall, the cleaning intervention modestly reduced
      potential exposure to risk factors associated with asthma mortality and morbidity
      in a way that can be implemented by most homeowners or renters, independent of
      education, income, or the ability to speak English.

PMID- 18059424
TI  - Assessment of exposure in epidemiological studies: the example of silica dust.
AB  - Exposure to crystalline silica ranks among the most frequent occupational
      exposures to an established human carcinogen. Health-based occupational exposure
      limits can only be derived from a reliable dose-response relationship. Although
      quartz dust seems to be a well-measurable agent, several uncertainties in the
      quantification of exposure to crystalline silica can bias the risk estimates in
      epidemiological studies. This review describes the silica-specific methodological
      issues in the assessment of exposure. The mineralogical forms of silica, the
      technologies applied to generate dust, protective measures, and co-existing
      carcinogens are important parameters to characterize the exposure condition of an
      occupational setting. Another methodological question concerns the measurement of
      the respirable dust fraction in the worker's breathing zone and the determination
      of the quartz content in that fraction. Personal devices have been increasingly
      employed over time, whereas norms for the measurement of respirable dust have
      been defined only recently. Several methods are available to analyse the content
      of crystalline silica in dust with limits of quantitation close to environmental
      exposure levels. For epidemiological studies, the quartz content has frequently
      not been measured but only calculated. To develop a silica-dust database for
      epidemiological purposes, historical dust concentrations sampled with different
      devices and measured as particle numbers have to be converted in a common
      exposure metric. For the development of a job-exposure matrix (JEM), missing
      historical data have to be estimated to complete the database over time. Unknown
      but frequently high-exposure levels of the past contribute largely to the
      cumulative exposure of a worker. Because the establishment of a JEM is crucial
      for risk estimates, sufficient information should be made accessible to allow an
      estimation of the uncertainties in the assessment of exposure to crystalline
      silica. The impressive number of silica dust measurements and the evaluation of
      methodological uncertainties allow recommendations for a best practice of
      exposure assessment for epidemiological studies.

PMID- 18059425
TI  - Relationships between levels of volatile organic compounds in air and blood from
      the general population.
AB  - The relationships between levels of volatile organic compounds (VOCs) in blood
      and air have not been well characterized in the general population where exposure
      concentrations are generally at parts per billion levels. This study investigates
      relationships between the levels of nine VOCs, namely, benzene, chloroform, 1,4
      dichlorobenzene, ethylbenzene, methyl tert-butyl ether (MTBE), tetrachloroethene,
      toluene, and m-/p- and o-xylene, in blood and air from a stratified random sample
      of the general US population. We used data collected from 354 participants,
      including 89 smokers and 265 nonsmokers, aged 20-59 years, who provided samples
      of blood and air in the National Health and Nutrition Examination Survey (NHANES)
      1999-2000. Demographic and physiological characteristics were obtained from self
      reported information; smoking status was determined from levels of serum
      cotinine. Multiple linear regression models were used to investigate the
      relationships between VOC levels in air and blood, while adjusting for effects of
      smoking and demographic factors. Although levels of VOCs in blood were positively
      correlated with the corresponding air levels, the strength of association (R(2))
      varied from 0.02 (ethylbenzene) to 0.68 (1,4-DCB). Also the blood-air
      relationships of benzene, toluene, ethylbenzene, and the xylenes (BTEX) were
      influenced by smoking, exposure-smoking interactions, and by gender, age, and
      BMI, whereas those of the other VOCs were not. Interestingly, the particular
      exposure-smoking interaction for benzene was different from those for toluene,
      ethylbenzene, and the xylenes. Whereas smokers retained more benzene in their
      blood at increasing exposure levels, they retained less toluene, ethylbenzene,
      and xylenes at increasing exposure levels. Investigators should consider
      interaction effects of exposure levels and smoking when exploring the blood-air
      relationships of the BTEX compounds in the general population.

PMID- 18059426
TI  - A scripted activity study of the impact of protective advice on personal exposure
      to ultra-fine and fine particulate matter and volatile organic compounds.
AB  - We evaluated the impact on personal exposure to air pollutants of following
      advice which typically accompanies air quality advisories and indices. Scripts
      prescribed the time, location, duration and nature of activities intended to
      simulate daily activity patterns for adults and children. Scripts were paired
      such that one individual would proceed with usual activities (base scenario),
      whereas the other (intervention scenario) would alter activities as if following
      advice. Other than commuting, where the intervention group walked or used public
      transportation rather than riding in personal vehicles, this group generally
      spent less time outdoors. Ultra-fine particles (UFPs), particulate matter of
      median aerodynamic diameter less than 2.5 mum (PM(2.5)) and total volatile
      organic compounds (VOCs) were measured using samplers carried by individuals
      during the course of daily activities. During daytime activities (e.g., work,
      daycare) constituting the largest share of sampling time (approximately 6 h per
      day), the intervention group experienced a 14% reduction in exposure to UFPs
      (P=0.01), a 21% reduction in exposure to PM(2.5) (P=0.08), and an 86% increase in
      exposure to VOCs (P=0.02). Other findings included an 89% increase in exposure to
      UFPs (P=0.02) and a threefold increase in exposure to VOCs (P=0.08) in the
      intervention group during evening cooking. Following smog advisory advice results
      in reduced exposures to some pollutants, while at the same time increasing
      exposure to others. Advice needs to be refined giving consideration to overall
      personal exposure.

PMID- 18059427
TI  - Serum dioxin levels in residents of Calcasieu and Lafayette parishes, Louisiana
      with comparison to the US population.
AB  - The Agency for Toxic Substances and Disease Registry (ATSDR) used a cross
      sectional study to compare the serum dioxin toxic equivalent (TEQ) levels of a
      population-based representative sample of Calcasieu Parish residents aged 15
      years and older to a similar group of residents of Lafayette Parish with less
      industrial facilities. Serum dioxins consisted of polychlorinated dibenzo-p
      dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated
      biphenyls. Overall, the mean and distribution of serum dioxin TEQ level in
      residents of both parishes were similar by age groups (15-29 years, 30-44 years,
      45-59 years, and 60 year and older). When the Calcasieu Parish area was further
      divided based on distance to three industrial areas, the mean dioxin TEQ levels
      were similar. Serum dioxin TEQ levels in residents of both parishes increased
      with age. Calcasieu Parish residents who reported having eaten locally caught
      fish, smoked cigarettes, worked in an occupation with potential exposure, or used
      pesticides had dioxin levels similar to Lafayette Parish residents who reported
      these activities. African Americans had higher dioxin levels than Caucasians in
      Lafayette Parish and both races in Calcasieu Parish. The congener profiles were
      similar in residents of both parishes. When the combined Calcasieu and Lafayette
      Parish data were compared by age group to the National Health and Nutrition
      Examination Survey (NHANES) 2001-2002 data, the geometric means for the dioxin
      levels in the combined Parish data set were significantly lower than the NHANES
      data in all age groups (all P-values <0.0001), except the oldest age group where
      the significance level is marginal (P=0.067). The various percentiles of the
      youngest age group of the combined parish data were also significantly lower than
      those in NHANES. Since the combined parish dioxin levels were below a
      representative sampling of the US population, there is no increase in serum
      dioxin concentrations in both the parishes.

PMID- 18059428
TI  - Probabilistic estimation of dietary exposure of the general Japanese population
      to dioxins in fish, using region-specific fish monitoring data.
AB  - Many studies show that dietary consumption of fish is the greatest contributor to
      dioxin exposure of humans in Japan. To establish a link between ocean
      contamination and human exposure to dioxins in fish, we proposed a method of
      estimating exposure by integrating region-specific measured concentrations of
      dioxins in fish samples and information on the production and import-export
      volumes of fish. The advantage over "total diet studies" (TDS) was that the
      proposed method could analyze the impact of the geographical variability of ocean
      contamination on human exposure to dioxins in fish; this may help us to apply
      more effective measures against dioxin exposure. Probabilistic distributions
      (probability density functions (PDFs)) were assigned to express the variability
      in the results of monitoring dioxin concentrations in fish from coastal areas
      divided according to prefecture, and from offshore and distant waters and
      imported sources. The Monte Carlo technique was applied for probabilistic
      estimation of dietary exposure of the general Japanese population to dioxins in
      fish. The mean and 5th to 95th percentile range of dietary exposure were
      estimated, respectively, as 67.12 and 22.65-184.35 pg toxic equivalent per day.
      Sensitivity analysis showed that some specific coastal areas with higher dioxin
      levels in fish and some with larger production volumes of fish impacted more than
      others to total exposure and may thus attract priority in the implementation of
      dioxin abatement measures.

PMID- 18059430
TI  - Spreading depression in the brainstem of the adult rat: electrophysiological
      parameters and influences on regional brainstem blood flow.
AB  - Cortical spreading depression is a pathophysiological excitation wave that occurs
      during pathophysiological brain conditions such as ischemic brain infarction,
      migraine aura, and others. Judged from experiments in rodents, the brainstem is
      thought to be comparatively resistant to the generation of spreading depression.
      However, because spreading depression can be elicited in the brainstem of rat
      pups after superfusing the brainstem with solutions enhancing excitability, we
      reinvestigated spreading depression in the brainstem of the adult rat. Based on
      theoretical predictions indicating a major role of extracellular potassium in
      susceptibility to spreading depression, we used conditioning solutions in which
      chloride ions were replaced by acetate and tetraethylammonium chloride and a
      small amount of KCl were added. Under these conditions, spreading depression was
      reproducibly elicited in the brainstem either by topical application of KCl
      crystals to the brainstem surface or by local microinjection of KCl into the
      brainstem. The direct current shifts so elicited were accompanied by typical
      elevation of extracellular potassium ions, propagated in the brainstem, and were
      prevented by MK-801, an N-methyl D-aspartate blocker. During spreading
      depression, the regional blood flow in the brainstem was transiently increased.
      In addition, systemic arterial blood pressure, but not the heart rate, was
      transiently enhanced. In the nonconditioned brainstem, KCl stimulation neither
      elicited spreading depression nor induced changes in regional blood flow and
      blood pressure. These data show that proper conditioning renders the brainstem
      susceptible to spreading depression, and that spreading depression at this site
      elicits changes in local circulation and systemic blood pressure.

PMID- 18059431
TI  - Functional reactivity of cerebral capillaries.
AB  - The spatiotemporal evolution of cerebral microcirculatory adjustments to
      functional brain stimulation is the fundamental determinant of the functional
      specificity of hemodynamically weighted neuroimaging signals. Very little data,
      however, exist on the functional reactivity of capillaries, the vessels most
      proximal to the activated neuronal population. Here, we used two-photon laser
      scanning microscopy, in combination with intracranial electrophysiology and
      intravital video microscopy, to explore the changes in cortical hemodynamics, at
      the level of individual capillaries, in response to steady-state forepaw
      stimulation in an anesthetized rodent model. Overall, the microcirculatory
      response to functional stimulation was characterized by a pronounced decrease in
      vascular transit times (20%+/-8%), a dilatation of the capillary bed (10.9%+/
      1.2%), and significant increases in red blood cell speed (33.0%+/-7.7%) and flux
      (19.5%+/-6.2%). Capillaries dilated more than the medium-caliber vessels,
      indicating a decreased heterogeneity in vessel volumes and increased blood flow
      carrying capacity during neuronal activation relative to baseline. Capillary
      dilatation accounted for an estimated approximately 18% of the total change in
      the focal cerebral blood volume. In support of a capacity for focal
      redistribution of microvascular flow and volume, significant, though less
      frequent, local stimulation-induced decreases in capillary volume and erythrocyte
      speed and flux also occurred. The present findings provide further evidence of a
      strong functional reactivity of cerebral capillaries and underscore the
      importance of changes in the capillary geometry in the hemodynamic response to
      neuronal activation.

PMID- 18059432
TI  - Cerebral blood flow autoregulation in experimental liver failure.
AB  - Patients with acute liver failure (ALF) display impairment of cerebral blood flow
      (CBF) autoregulation, which may contribute to the development of fatal
      intracranial hypertension, but the pathophysiological mechanism remains unclear.
      In this study, we examined whether loss of liver mass causes impairment of CBF
      autoregulation. Four rat models were chosen, each representing different aspects
      of ALF: galactosamine (GlN) intoxication represented liver necrosis, 90%
      hepatectomy (PHx90) represented reduction in liver mass, portacaval anastomosis
      (PCA) represented shunting of blood/toxins into the systemic circulation thus
      mimicking intrahepatic shunting in ALF, PCA+NH(3) provided information about the
      additional effects of hyperammonemia Rats were intubated and sedated with
      pentobarbital. We measured CBF with laser Doppler, intracranial pressure (ICP)
      was measured in the fossa posterior and registered with a pressure transducer,
      brain water was measured using the wet-to-dry method, and cerebral
      glutamine/glutamate was measured enzymatically. The CBF autoregulatory index in
      both the GlN and PHx90 groups differed significantly from the control group.
      Conversely, CBF autoregulation was intact in the PCA and PCA+NH(3) groups despite
      high arterial ammonia, high cerebral glutamine concentration, and increased CBF
      and ICP. Increased water content of the brainstem or cerebellum was not
      associated with defective CBF autoregulation. In conclusion, impairment of CBF
      autoregulation is not caused by brain edema/high ICP. Nor does portacaval
      shunting or hyperammonemia impair autoregulation. Rather, massive liver necrosis
      and reduced liver mass are associated with loss of CBF autoregulation.

PMID- 18059433
TI  - Changes in autophagy after traumatic brain injury.
AB  - Autophagy is the chief machinery for bulk degradation of superfluous or aberrant
      cytoplasmic components. This study used the rat moderate fluid percussion injury
      model to investigate whether the autophagy pathway plays a key role after
      traumatic brain injury (TBI). Induction of autophagy is manifested by
      accumulation of autophagosomes (APs), observable under transmission electron
      microscopy (EM). Two hallmarks of autophagy, i.e., the microtubule-associated
      protein light chain 3 (LC3)-II and the autophagy-related gene (ATG)12-ATG5
      conjugates, were explored by biochemical and confocal microscopic analyses of
      brain tissues. Under EM, both APs and autolysosomes were markedly accumulated in
      neurons from 4 h onward after TBI. Western blot analysis showed that ATG12-ATG5
      conjugate was markedly redistributed during 5 to 15 days in brain tissues after
      TBI. LC3-II conjugate was initially unchanged but was drastically upregulated
      from 24 h onward in the pre-AP-containing fraction after TBI. LC-3 immunostaining
      was mainly located in living neurons under confocal microscopy. These results
      clearly show that the autophagy pathway is persistently activated after TBI.
      Because the autophagy pathway is the chief machinery for bulk elimination of
      aberrant cell components, we propose that activation of this pathway serves as a
      protective mechanism for maintaining cellular homeostasis after TBI.

PMID- 18059434
TI  - Improving PET receptor binding estimates from Logan plots using principal
      component analysis.
AB  - This work reports a principal component analysis (PCA)-based approach for
      reducing bias in distribution volume ratio (DVR) estimates from Logan plots in
      positron emission tomography (PET). Comparison has been made of all existing bias
      removal methods with the proposed PCA method, for both single-estimate PET
      studies and intervention studies where pre- and post-intervention estimates are
      made. Bias in Logan-based DVR estimates is because of the noise in the PET time
      activity curves (TACs) that propagates as correlated errors in dependent and
      independent variables of the Logan equation. Intervention studies show this same
      bias but also higher variance in DVR estimates. In this work, noise in the TACs
      was reduced by fitting the curves to a low-dimension PCA-based linear model,
      leading to reduced bias and variance in DVR. For validating the approach, TACs
      with realistic noise were simulated for a 11C-labeled tracer with carfentanil
      (CFN)-like kinetics for both single-measurement and intervention studies.
      Principal component analysis and existing methods were applied to the simulated
      data and their performance was compared by statistical analysis. The results
      indicated that existing methods either removed only part of the bias or reduced
      bias at the expense of precision. The proposed method removed approximately 90%
      of the bias while also improving precision in both single- and dual-measurement
      simulations. After validation of the proposed method in simulations, PCA, along
      with the existing methods, was applied to human [11C]CFN data acquired for both
      single estimation of DVR and dual-estimation intervention studies. Similar
      results were observed in human scans as were seen in the simulation studies.

PMID- 18059435
TI  - The influence of subthalamic nucleus lesions on sign-tracking to stimuli paired
      with food and drug rewards: facilitation of incentive salience attribution?
AB  - It is well known that the subthalamic nucleus (STN) plays an important role in
      regulating motor function, but recent studies suggest the STN is also involved in
      regulating motivated behavior. For example, bilateral lesions of the STN increase
      motivation for both food and cocaine as assessed by 'breakpoint' on a progressive
      ratio schedule. However, the psychological mechanism(s) by which STN lesions
      increase motivation for rewards is unknown. We hypothesized that STN lesions
      might influence one specific component of motivation, the attribution of
      incentive value (incentive salience) to reward-related cues. We tested this
      hypothesis by quantifying the ability of a discrete cue that had been paired with
      the non-contingent delivery of either food or cocaine to elicit approach towards
      it (ie, to produce a 'sign-tracking' conditioned response, CR). STN lesions made
      prior to training increased asymptotic levels of sign-tracking behavior directed
      towards a cue paired with either food or cocaine. In addition, when STN lesions
      were made after animals had already undergone Pavlovian training, and animals
      were tested under extinction conditions, the STN lesion still facilitated a sign
      tracking CR. Finally, reintroduction of the US (food) following extinction
      immediately restored robust sign-tracking behavior in animals with STN lesions.
      We speculate, therefore, that the STN is part of a neural system that moderates
      the amount of incentive salience attributed to reward-related stimuli. Activity
      in this neural system may help mitigate the development of compulsive behavioral
      disorders, such as addiction, which are characterized by pathological control
      over behavior by reward-associated cues.

PMID- 18059436
TI  - Context-specific reversal of cocaine sensitization by the CB1 cannabinoid
      receptor antagonist rimonabant.
AB  - The CB(1) cannabinoid receptor is implicated in the rewarding properties of many
      drugs of abuse, including cocaine. While CB(1) receptor involvement in the acute
      rewarding properties of cocaine is controversial, CB(1) antagonists such as
      SR141716 (rimonabant) have clearly been found to prevent cue- and cocaine
      elicited reinstatement of cocaine self-administration in rodents. Here we
      demonstrate the novel involvement of CB(1) receptors in the maintenance of
      behavioral sensitization to cocaine in C57BL/6 mice. Consistent with previous
      reports, the induction of locomotor sensitization following repeated daily
      cocaine was not prevented by systemic pretreatment of either rimonabant, Delta(9)
      tetrahydrocannabinol (THC), or a 1:1 mixture of THC and cannabidiol (CBD). In
      contrast, established cocaine sensitization was markedly disrupted following
      subchronic treatment with rimonabant alone. This effect was notably context
      dependent, in that rimonabant did not diminish established cocaine sensitization
      if delivered in the home cage, but only if the rimonabant-injected mice were
      exposed to activity chambers previously paired with cocaine. These findings are
      consistent with CB(1) receptor involvement in conditioned cocaine-seeking
      behaviors, and further suggest that endocannabinoid (eCB)-mediated synaptic
      plasticity may act specifically within drug-paired environments to maintain
      cocaine-directed behavioral responses.

PMID- 18059437
TI  - Postnatal phencyclidine administration selectively reduces adult cortical
      parvalbumin-containing interneurons.
AB  - Transient postnatal NMDA receptor blockade by phencyclidine (PCP), ketamine, or
      MK-801 induces developmental neuroapoptosis and adult behavioral deficits, which
      resemble abnormal human behaviors typically present in schizophrenia. This study
      tested the hypothesis that PCP-induced developmental apoptosis causes a specific
      deficit of GABAergic interneurons containing parvalbumin (PV), calretinin (CR),
      or calbindin (CB). Young adult (PND56) rats that were given a single dose of PCP
      (10 mg/kg) on PND7 exhibited no densitometric change of either CR or CB neurons
      in any brain region studied, but demonstrated a selective deficit of PV
      containing neurons in the superficial layers (II-IV) of the primary somatosensory
      (S1), motor (M), and retrosplenial cortices, but not in the striatum (CPu) or
      hippocampus. Further, CR and CB neurons, which were expressed at the time of PCP
      administration, showed no colocalization with cellular markers of apoptosis
      (terminal dUTP nick-end labeling (TUNEL) of broken DNA or cleaved caspase-3),
      indicating that CR- and CB-containing neurons were protected from the toxic
      effect of PCP and survived into adulthood. This suggests that the deletion of PV
      neurons occurred during development, but cleaved caspase-3 showed no
      colocalization with BrdU, a specific marker of S-phase proliferation. These data
      suggest that the loss of PV-containing neurons was not due to an effect of PCP on
      proliferating neurons, but rather an effect on post-mitotic neurons. The
      developmental dependence and neuronal specificity of this effect of PCP provides
      further evidence that this model may be valuable in exploring the pathophysiology
      of schizophrenia.

PMID- 18059438
TI  - N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5
      HT1A agonist, as a putative mediator of quetiapine's antidepressant activity.
AB  - Quetiapine is an atypical antipsychotic drug that is also US FDA approved for
      treating bipolar depression, albeit by an unknown mechanism. To discover the
      potential mechanism for this apparently unique action, we screened quetiapine,
      its metabolite N-Desalkylquetiapine, and dibenzo[b,f][1,4]thiazepine-11(10-H)-one
      (DBTO) against a large panel of G-protein-coupled receptors, ion channels, and
      neurotransmitter transporters. DBTO was inactive at all tested molecular targets.
      N-Desalkylquetiapine had a high affinity (3.4 nM) for the histamine H(1) receptor
      and moderate affinities (10-100 nM) for the norepinephrine reuptake transporter
      (NET), the serotonin 5-HT(1A), 5-HT(1E), 5-HT(2A), 5-HT(2B), 5-HT(7) receptors,
      the alpha(1B)-adrenergic receptor, and the M(1), M(3), and M(5) muscarinic
      receptors. The compound had low affinities (100-1000 nM) for the 5-HT(1D), 5
      HT(2C), 5-HT(3), 5-HT(5), 5-HT(6), alpha(1A), alpha(2A), alpha(2B), alpha(2C),
      H(2), M(2), M(4), and dopamine D(1), D(2), D(3), and D(4) receptors. N
      Desalkylquetiapine potently inhibited human NE transporter with a K(i) of 12 nM,
      about 100-fold more potent than quetiapine itself. N-Desalkylquetiapine was also
      10-fold more potent and more efficacious than quetiapine at the 5-HT(1A)
      receptor. N-Desalkylquetiapine was an antagonist at 5-HT(2A), 5-HT(2B), 5-HT(2C),
      alpha(1A), alpha(1D), alpha(2A), alpha(2C), H(1), M(1), M(3), and M(5) receptors.
      In the mouse tail suspension test, N-Desalkylquetiapine displayed potent
      antidepressant-like activity in VMAT2 heterozygous mice at doses as low as 0.1
      mg/kg. These data strongly suggest that the antidepressant activity of quetiapine
      is mediated, at least in part, by its metabolite N-Desalkylquetiapine through NET
      inhibition and partial 5-HT(1A) agonism. Possible contributions of this
      metabolite to the side effects of quetiapine are discussed.

PMID- 18059439
TI  - Cortical hypoexcitability in chronic smokers? A transcranial magnetic stimulation
      study.
AB  - Studies in animal models and humans indicate that chronic nicotine intake
      influences neuronal excitability, resulting in functional and structural CNS
      changes. The aim of the present study was to explore human primary motor cortex
      (M1) excitability with transcranial magnetic stimulation (TMS) in chronic
      smokers. A total of 44 right-handed volunteers, aged 20-30 years, participated in
      the study. Chronic smokers were compared with age- and sex-matched healthy
      nonsmokers. We tested cortical excitability with single- and paired-pulse TMS to
      the left M1 and short-latency afferent inhibition (SAI) by combining median nerve
      stimulation and motor cortex TMS. Compared with nonsmoking controls, chronic
      smokers showed a significantly larger amount of SAI, which is thought to depend
      upon the activity of cholinergic inhibitory circuits produced by somatosensory
      inputs. Moreover, TMS-evoked inhibitory cortical silent periods were prolonged,
      whereas paired-pulse intracortical facilitation and motor-evoked potentials
      during moderate contraction were reduced. The results suggest that chronic
      nicotine intake may not only strengthen cholinergic inhibitory circuits, but
      could also be associated with enhanced inhibitory and reduced facilitatory
      mechanism of specific neuronal circuits in motor cortex. These changes may form a
      physiological basis for neurobiological and behavioral variations associated with
      chronic smoking.

PMID- 18059440
TI  - Attenuation of cue-induced heroin-seeking behavior by cannabinoid CB1 antagonist
      infusions into the nucleus accumbens core and prefrontal cortex, but not
      basolateral amygdala.
AB  - As with other drugs of abuse, heroin use is characterized by a high incidence of
      relapse following detoxification that can be triggered by exposure to conditioned
      stimuli previously associated with drug availability. Recent findings suggest
      that cannabinoid CB(1) receptors modulate the motivational properties of heroin
      conditioned stimuli that induce relapse behavior. However, the neural substrates
      through which CB(1) receptors modulate cue-induced heroin seeking have not been
      elucidated. In this study, we evaluated alterations in cue-induced reinstatement
      of heroin-seeking behavior produced by infusions of the CB(1) receptor antagonist
      SR 141716A (0, 0.3 and 3 microg per side) delivered into the prefrontal cortex
      (PFC), nucleus accumbens (NAC), and basolateral amygdala (BLA) of rats. Results
      show that following extinction of operant behavior the presentation of a
      discriminative stimulus conditioned to heroin availability reinstated
      nonreinforced lever pressing to levels comparable to preextinction levels. Intra
      PFC SR 141716A dose-dependently reduced cue-induced reinstatement of heroin
      seeking, with a significant reduction following the 3 microg per side dose. In
      the NAC, both SR 141716A doses induced a significant reduction in cue-induced
      reinstatement, with the highest dose completely blocking the effect of the cue.
      In contrast, intra-BLA SR 141716A did not alter cue-induced reinstatement of
      responding while systemic administration of this antagonist (3 mg/kg, i.p.)
      significantly blocked cue-induced reinstatement in all three-placement groups
      (BLA, PFC, and NAC). These findings provide new insights into the neural
      mechanisms through which CB(1) receptors modulate the motivational properties of
      heroin-associated cues inducing relapse.

PMID- 18059441
TI  - Neural pathways underlying lactate-induced panic.
AB  - Panic disorder is a severe anxiety disorder characterized by susceptibility to
      induction of panic attacks by subthreshold interoceptive stimuli such as 0.5 M
      sodium lactate infusions. Although studied for four decades, the mechanism of
      lactate sensitivity in panic disorder has not been understood. The dorsomedial
      hypothalamus/perifornical region (DMH/PeF) coordinates rapid mobilization of
      behavioral, autonomic, respiratory and endocrine responses to stress, and rats
      with disrupted GABA inhibition in the DMH/PeF exhibit panic-like responses to
      lactate, similar to panic disorder patients. Utilizing a variety of anatomical
      and pharmacological methods, we provide evidence that lactate, via osmosensitive
      periventricular pathways, activates neurons in the compromised DMH/PeF, which
      relays this signal to forebrain limbic structures such as the bed nucleus of the
      stria terminalis to mediate anxiety responses, and specific brainstem sympathetic
      and parasympathetic pathways to mediate the respiratory and cardiovascular
      components of the panic-like response. Acutely restoring local GABAergic tone in
      the DMH/PeF blocked lactate-induced panic-like responses. Autonomic panic-like
      responses appear to be a result of DMH/PeF-mediated mobilization of sympathetic
      responses (verified with atenolol) and resetting of the parasympathetically
      mediated baroreflex. Based on our findings, DMH/PeF efferent targets such as the
      C1 adrenergic neurons, paraventricular hypothalamus, and the central amygdala are
      implicated in sympathetic mobilization; the nucleus of the solitary tract is
      implicated in baroreflex resetting; and the parabrachial nucleus is implicated in
      respiratory responses. These results elucidate neural circuits underlying lactate
      induced panic-like responses and the involvement of both sympathetic and
      parasympathetic systems.

PMID- 18059442
TI  - A modular network model of aging.
AB  - Many fundamental questions on aging are still unanswered or are under intense
      debate. These questions are frequently not addressable by examining a single gene
      or a single pathway, but can best be addressed at the systems level. Here we
      examined the modular structure of the protein-protein interaction (PPI) networks
      during fruitfly and human brain aging. In both networks, there are two modules
      associated with the cellular proliferation to differentiation temporal switch
      that display opposite aging-related changes in expression. During fly aging,
      another couple of modules are associated with the oxidative-reductive metabolic
      temporal switch. These network modules and their relationships demonstrate (1)
      that aging is largely associated with a small number, instead of many network
      modules, (2) that some modular changes might be reversible and (3) that genes
      connecting different modules through PPIs are more likely to affect
      aging/longevity, a conclusion that is experimentally validated by Caenorhabditis
      elegans lifespan analysis. Network simulations further suggest that aging might
      preferentially attack key regulatory nodes that are important for the network
      stability, implicating a potential molecular basis for the stochastic nature of
      aging.

PMID- 18059443
TI  - Q-bio 2007: a watershed moment in modern biology.

PMID- 18059444
TI  - Systems metabolic engineering of Escherichia coli for L-threonine production.
AB  - Amino-acid producers have traditionally been developed by repeated random
      mutagenesis owing to the difficulty in rationally engineering the complex and
      highly regulated metabolic network. Here, we report the development of the
      genetically defined L-threonine overproducing Escherichia coli strain by systems
      metabolic engineering. Feedback inhibitions of aspartokinase I and III (encoded
      by thrA and lysC, respectively) and transcriptional attenuation regulations
      (located in thrL) were removed. Pathways for Thr degradation were removed by
      deleting tdh and mutating ilvA. The metA and lysA genes were deleted to make more
      precursors available for Thr biosynthesis. Further target genes to be engineered
      were identified by transcriptome profiling combined with in silico flux response
      analysis, and their expression levels were manipulated accordingly. The final
      engineered E. coli strain was able to produce Thr with a high yield of 0.393 g
      per gram of glucose, and 82.4 g/l Thr by fed-batch culture. The systems metabolic
      engineering strategy reported here may be broadly employed for developing
      genetically defined organisms for the efficient production of various
      bioproducts.

PMID- 18059445
TI  - Capturing cell-fate decisions from the molecular signatures of a receptor
      dependent signaling response.
AB  - We examined responses of the B-cell antigen receptor-dependent intracellular
      signaling network to targeted perturbations induced through siRNA-mediated
      depletion of select signaling intermediates. The constituent nodes displayed
      graded sensitivities, which resulted from the differential effects of
      perturbations on the kinetic and quantitative aspects of phosphorylation at each
      node. By taking the rate of initial phosphorylation, rate of subsequent
      dephosphorylation, and the total intensity of phosphorylation at each node as
      separate signaling parameters, we generated data-driven models that accurately
      predicted the cellular responses of apoptosis, proliferation, and cytokine
      secretion. Importantly, the effects of perturbation on the primary target alone
      did not yield successful models. Rather, it also required incorporation of
      secondary effects on many other nodes. A significant feature of these models was
      that the three signaling parameters derived from each node functioned largely as
      independent entities, making distinctive contributions to the cellular response.
      Thus, the kinetic and quantitative features of phosphorylation at a node appear
      to play discrete roles during signal processing.

PMID- 18059447
TI  - 'Tis the season...

PMID- 18059446
TI  - Evolvable signaling networks of receptor tyrosine kinases: relevance of
      robustness to malignancy and to cancer therapy.
AB  - Robust biological signaling networks evolved, through gene duplications, from
      simple, relatively fragile cascades. Architectural features such as layered
      configuration, branching and modularity, as well as functional characteristics
      (e.g., feedback control circuits), enable fail-safe performance in the face of
      internal and external perturbations. These universal features are exemplified
      here using the receptor tyrosine kinase (RTK) family. The RTK module is richly
      mutated and overexpressed in human malignancies, and pharmaceutical interception
      of its signaling effectively retards growth of specific tumors. Therapy-induced
      interception of RTK-signaling pathways and the common evolvement of drug
      resistance are respectively considered here as manifestations of fragility and
      plasticity of robust networks. The systems perspective we present views
      pathologies as hijackers of biological robustness and offers ways for identifying
      fragile hubs, as well as strategies to overcome drug resistance.

PMID- 18059448
TI  - Three-dimensional intricacies in protein-DNA recognition and transcriptional
      control.

PMID- 18059449
TI  - A monkey wrench in the kinase machine.

PMID- 18059450
TI  - Merging the RNA and DNA worlds.

PMID- 18059451
TI  - TIRF(ing) reveals Msh2-Msh6 surfing on DNA.

PMID- 18059454
TI  - Urinary biomarkers in the early diagnosis of acute kidney injury.
AB  - A change in the serum creatinine is not sensitive for an early diagnosis of acute
      kidney injury. We evaluated urinary levels of matrix metalloproteinase-9 (MMP-9),
      N-acetyl-beta-D-glucosaminidase (NAG), and kidney injury molecule-1 (KIM-1) as
      biomarkers for the detection of acute kidney injury. Urine samples were collected
      from 44 patients with various acute and chronic kidney diseases, and from 30
      normal subjects in a cross-sectional study. A case-control study of children
      undergoing cardio-pulmonary bypass surgery included urine specimens from each of
      20 patients without and with acute kidney injury. Injury was defined as a greater
      than 50% increase in the serum creatinine within the first 48 h after surgery.
      The biomarkers were normalized to the urinary creatinine concentration at 12, 24,
      and 36 h after surgery with the areas under the receiver-operating characteristic
      curve compared for performance. In the cross-sectional study, the area under the
      curve for MMP-9 was least sensitive followed by KIM-1 and NAG. Combining all
      three biomarkers achieved a perfect score diagnosing acute kidney injury. In the
      case-control study, KIM-1 was better than NAG at all time points, but combining
      both was no better than KIM-1 alone. Urinary MMP-9 was not a sensitive marker in
      the case-control study. Our results suggest that urinary biomarkers allow
      diagnosis of acute kidney injury earlier than a rise in serum creatinine.

PMID- 18059455
TI  - Arkadia regulates TGF-beta signaling during renal tubular epithelial to
      mesenchymal cell transition.
AB  - Transforming growth factor-beta (TGF-beta) signaling has been linked with tubular
      epithelial to mesenchymal cell transition. In this study, we examined the role of
      Arkadia, an E3 ubiquitin ligase that is critically required for TGF-beta
      signaling during epithelial to mesenchymal cell transition. We found that when
      normal human renal tubular epithelial cells in culture were stimulated with TGF
      beta1, which increased their levels of Arkadia, Smurf2, TGF-beta type I receptor
      (TbetaRI), and Smad7 mRNA, but had low levels of Smad7 protein. When these cells
      were preincubated with Arkadia siRNA (small interfering RNA) and lactacystin (an
      inhibitor of proteasomal degradation), the TGF-beta(1) induced expression of
      Smad7, alpha-smooth muscle actin, and E-cadherin was partly reversed, but the
      expression of TbetaRI protein and Smad7 mRNA was not affected. In contrast,
      Smurf2 siRNA had no influence on the expression of these targets. Our studies
      suggest that Arkadia stimulates renal tubular epithelial to mesenchymal cell
      transition through degradation of Smad7.

PMID- 18059456
TI  - A wearable hemofilter for continuous ambulatory ultrafiltration.
AB  - Ultrafiltration is effective for treating fluid overload, but there are no
      suitable machines for ambulatory treatment. This study summarizes the use of a
      light-weight wearable continuous ambulatory ultrafiltration device consisting of
      a hollow fiber hemofilter, a battery operated pulsatile pump, and two micropumps
      to control heparin administration and ultrafiltration. Six volume-overloaded
      patients underwent ultrafiltration for 6 h with treatment discontinued in one
      patient due to a clotted catheter. Blood flow averaged 116 ml min(-1), the
      ultrafiltration rate ranged from 120-288 ml h(-1) with about 150 mmol of sodium
      removed. Blood pressure, pulse, and biochemical parameters remained stable with
      no significant hemolysis or complications. Our data show that the wearable
      hemofilter appears to be safe, effective, and practical for patients. This device
      could have a major impact on the quality of life of fluid-overloaded patients
      with heart failure. Additional studies will be needed to confirm these initial
      promising results.

PMID- 18059457
TI  - 24-h uric acid excretion and the risk of kidney stones.
AB  - There is uncertainty about the relation between 24-h urinary uric acid excretion
      and the risk of calcium oxalate nephrolithiasis. In addition, the risk associated
      with different levels of other urinary factors needs clarification. We performed
      a cross-sectional study of 24-h urine excretion and the risk of kidney stone
      formation in 3350 men and women, of whom 2237 had a history of nephrolithiasis.
      After adjusting for other urinary factors, urinary uric acid had a significant
      inverse association with stone formation in men, a marginal inverse association
      with risk in younger women, and no association in older women. The risk of stone
      formation in men and women significantly rose with increasing urine calcium and
      oxalate, and significantly decreased with increasing citrate and urine volume,
      with the change in risk beginning below the traditional normal thresholds. Other
      urinary factors were also associated with risk, but this varied by age and
      gender. Our study does not support the prevailing belief that higher urine uric
      acid excretion increases the risk for calcium oxalate stone formation. In
      addition, the current definitions of normal levels for urinary factors need to be
      re-evaluated.

PMID- 18059458
TI  - High prevalence of chronic kidney disease in Thailand.
AB  - We describe the prevalence of stage III and IV chronic kidney disease in Thailand
      from a representative sample of individuals aged 35 years and above using a
      stratified, multistage, cluster-sampling method. Population estimates were
      calculated by applying sampling weights from the 2000 Thai census. Glomerular
      filtration rates were estimated from serum creatinine using the Cockroft-Gault
      and the simplified Modification of Diet in Renal Disease (MDRD) formulae. The
      prevalence of stage III disease among individuals aged 35 years and above was
      estimated to be about 20% using the Cockroft-Gault formula and about 13% from the
      MDRD formula. Stage IV disease was present in about 0.9 and 0.6% of this
      population using the respective formulae. The highest prevalence rates were
      observed in less well-developed rural areas and the lowest in developed urban
      areas. The prevalence of chronic kidney disease was significantly higher than
      that reported in individuals over 40 years old from the United States for both
      stage III and IV disease and higher than the reported incidence in Taiwan and
      Australia. This high prevalence of chronic kidney disease in Thailand has obvious
      implications for the health of its citizens and for the allocation of health-care
      resources.

PMID- 18059459
TI  - The L1 cell adhesion molecule is a potential biomarker of human distal nephron
      injury in acute tubular necrosis.
AB  - The L1 cell adhesion molecule (CD171) is a multidomain membrane glycoprotein of
      the immunoglobulin superfamily. We evaluated its expression in human acute kidney
      injury and assessed its use as a tissue and urinary marker of acute tubular
      injury. Using immunohistochemical studies with antibodies to the extracellular or
      cytoplasmic domains, we compared L1 expression in normal kidneys in 24 biopsies
      taken from patients with acute tubular necrosis. L1 was found at the basolateral
      and the lateral membrane in all epithelial cells of the collecting duct in the
      normal kidney except for intercalated cells. In acute tubular necrosis, L1 lost
      its polarized distribution being found in both the basolateral and apical domains
      of the collecting duct. Further, it was induced in thick ascending limb and
      distal tubule cells. Apically expressed L1 found only when the cytoplasmic domain
      antibody was used in biopsy specimens of patients with acute tubular necrosis.
      The levels of urinary L1, normalized for creatinine, were significantly higher in
      all 24 patients with acute tubular necrosis compared to five patients with
      prerenal azotemia or to six patients with other causes of acute kidney injury.
      Our study shows that a soluble form of human L1 can be detected in the urine of
      patients with acute tubular necrosis and that this may be a marker of distal
      nephron injury.

PMID- 18059460
TI  - Reconstitution of a microtubule plus-end tracking system in vitro.
AB  - The microtubule cytoskeleton is essential to cell morphogenesis. Growing
      microtubule plus ends have emerged as dynamic regulatory sites in which
      specialized proteins, called plus-end-binding proteins (+TIPs), bind and regulate
      the proper functioning of microtubules. However, the molecular mechanism of plus
      end association by +TIPs and their ability to track the growing end are not well
      understood. Here we report the in vitro reconstitution of a minimal plus-end
      tracking system consisting of the three fission yeast proteins Mal3, Tip1 and the
      kinesin Tea2. Using time-lapse total internal reflection fluorescence microscopy,
      we show that the EB1 homologue Mal3 has an enhanced affinity for growing
      microtubule end structures as opposed to the microtubule lattice. This allows it
      to track growing microtubule ends autonomously by an end recognition mechanism.
      In addition, Mal3 acts as a factor that mediates loading of the processive motor
      Tea2 and its cargo, the Clip170 homologue Tip1, onto the microtubule lattice. The
      interaction of all three proteins is required for the selective tracking of
      growing microtubule plus ends by both Tea2 and Tip1. Our results dissect the
      collective interactions of the constituents of this plus-end tracking system and
      show how these interactions lead to the emergence of its dynamic behaviour. We
      expect that such in vitro reconstitutions will also be essential for the
      mechanistic dissection of other plus-end tracking systems.

PMID- 18059461
TI  - Coevolution with viruses drives the evolution of bacterial mutation rates.
AB  - Bacteria with greatly elevated mutation rates (mutators) are frequently found in
      natural and laboratory populations, and are often associated with clinical
      infections. Although mutators may increase adaptability to novel environmental
      conditions, they are also prone to the accumulation of deleterious mutations. The
      long-term maintenance of high bacterial mutation rates is therefore likely to be
      driven by rapidly changing selection pressures, in addition to the possible slow
      transition rate by point mutation from mutators to non-mutators. One of the most
      likely causes of rapidly changing selection pressures is antagonistic coevolution
      with parasites. Here we show whether coevolution with viral parasites could drive
      the evolution of bacterial mutation rates in laboratory populations of the
      bacterium Pseudomonas fluorescens. After fewer than 200 bacterial generations,
      25% of the populations coevolving with phages had evolved 10- to 100-fold
      increases in mutation rates owing to mutations in mismatch-repair genes; no
      populations evolving in the absence of phages showed any significant change in
      mutation rate. Furthermore, mutator populations had a higher probability of
      driving their phage populations extinct, strongly suggesting that mutators have
      an advantage against phages in the coevolutionary arms race. Given their
      ubiquity, bacteriophages may play an important role in the evolution of bacterial
      mutation rates.

PMID- 18059462
TI  - A microenvironmental model of carcinogenesis.
AB  - We propose that carcinogenesis requires tumour populations to surmount six
      distinct microenvironmental proliferation barriers that arise in the adaptive
      landscapes of normal and premalignant populations growing from epithelial
      surfaces. Somatic evolution of invasive cancer can then be viewed as a sequence
      of phenotypical adaptations to these barriers. The genotypical and phenotypical
      heterogeneity of cancer populations is explained by an equivalence principle in
      which multiple strategies can successfully adapt to the same barrier. This model
      provides a theoretical framework in which the diverse cancer genotypes and
      phenotypes can be understood according to their roles as adaptive strategies to
      overcome specific microenvironmental growth constraints.

PMID- 18059463
TI  - The psychosocial burden of hyperemesis gravidarum.
AB  - OBJECTIVE: To describe the psychosocial burden of hyperemesis gravidarum (HG) in
      a large cohort of affected women, focusing on previously unreported problems.
      STUDY DESIGN: Women with HG described their pregnancy history in an open-ended
      survey administered internationally through an HG website during 2003 to 2005.
      RESULT: Of the 808 participants, 626 (77.5%) were American. A large majority
      (82.8%) reported that HG caused negative psychosocial changes, consisting of (1)
      socioeconomic changes, for example, job loss or difficulties, (2) attitude
      changes including fear regarding future pregnancies and (3) psychiatric sequelae,
      for example, feelings of depression and anxiety, which for some continued
      postpartum. Women who reported that their health-care provider was uncaring or
      unaware of the severity of their symptoms were nearly twice as likely to report
      these psychiatric sequelae (odds ratio 1.86, 95% confidence interval 1.06 to
      3.29, P=0.032). CONCLUSION: Over 80% of a large cohort of women with HG reported
      that HG caused a negative psychosocial impact.

PMID- 18059464
TI  - Household knowledge and practices of newborn and maternal health in Haripur
      district, Pakistan.
AB  - OBJECTIVE: To learn about household maternal and newborn health knowledge and
      practices to aid the design of newborn programming within Save the Children's
      Haripur Program. STUDY DESIGN: In April, we conducted 43 semi-structured
      interviews (SSIs) and 34 focus group discussions among men, women of reproductive
      age and health service providers; in September, we added 21 SSIs among new
      mothers, new fathers and dais. Two investigators analyzed the findings according
      to themes within six care types: antenatal, delivery, immediate newborn, routine
      postpartum, special maternal and special newborn. RESULT: Findings indicated poor
      maternal diet and antenatal care-seeking. Home delivery with an untrained dai was
      the norm. Respondents knew about benefits of clean delivery, but rarely put
      knowledge into practice. Knowledge and practices for maintaining the newborn's
      warmth were good. Delayed initiation of breastfeeding, avoidance of colostrum and
      prelacteal feeding were almost universal. Unhygienic cord care, including an
      unclean cut and application of ghee on the cord-stump, was the norm. After
      delivery, mothers often maintained low fluid intake but otherwise reported
      healthy nutritional practices. Knowledge of some danger signs in newborns was
      common, but timely action upon recognition was not. CONCLUSION: Although the
      findings illustrate some beneficial practices, many reported practices are
      harmful to the newborn. These findings, consistent with the sparse existing data
      in Pakistan, inform program interventions for household-level behavioral change.

PMID- 18059465
TI  - Implementation of a 'Hypothermia for HIE' program: 2-year experience in a single
      NICU.
AB  - Hypothermia has been shown to be neuroprotective in some newborns with moderate
      to-severe perinatal hypoxic-ischemic encephalopathy (HIE). In 2006, the American
      Academy of Pediatrics recommended that institutions that choose to use
      therapeutic hypothermia do so in the context of a rigorous protocol, with
      systematic collection of patient data including neurodevelopmental follow-up. In
      this report, we describe our experience with implementation of a 'Hypothermia for
      HIE' program in a single tertiary care Neonatal Intensive Care Unit (NICU).
      Important components of the program include detailed protocols, staff and
      outreach education, early initiation of cooling in both inborn and outborn
      patients, maintaining stable hypothermia during neonatal transport, and
      comprehensive neurologic evaluation including serial EEGs, brain MRI and
      neurodevelopmental follow-up. In the first 2 years of the program, we have used
      hypothermia therapy in 21 patients, 18 with perinatal and 3 with early postnatal
      events leading to HIE. Eleven of fifteen outborn patients were cooled prior to
      and during transport, resulting in initiation of therapy 3 h sooner than if
      therapy had been delayed until arrival at our center. While lowering the body
      temperature of encephalopathic newborns is not difficult, addressing the complex
      medical problems of this vulnerable group of patients requires an experienced
      multidisciplinary team in regional referral centers.

PMID- 18059466
TI  - The epidemiology of atypical chronic lung disease in extremely low birth weight
      infants.
AB  - OBJECTIVE: To determine the incidence and associated complications of atypical
      chronic lung disease (ACLD) in extremely low birth weight infants. STUDY DESIGN:
      All infants born at Johns Hopkins Hospital between 1996 and 2001, with
      birthweight <1000 g, gestational age <31 weeks, no major anomalies or genetic
      syndromes, and living at least 21 days were eligible for inclusion. Data
      pertaining to demographics, hospital course, diagnosis of atypical chronic lung
      disease, patterns of surfactant use, complications of prematurity and severity of
      lung disease were collected. RESULT: Using inclusion criteria, 215 eligible
      infants were identified, of which 185 had hospital charts available for review.
      Twenty-eight infants (15%) met the criteria for atypical chronic lung disease. Of
      the remaining 157 infants, 57 patients met the criteria for mild bronchopulmonary
      dysplasia (BPD) (supplemental oxygen requirement at 28 days of life), 38 patients
      had moderate/severe BPD (supplemental oxygen requirement at both 28 days of life
      and 36 weeks post-menstrual age), and 38 infants did not have chronic lung
      disease. Infants with ACLD had much higher rates of sepsis (46%) and pneumothorax
      (18%) than infants in the comparison groups. CONCLUSION: Infants with respiratory
      distress syndrome in the first week of life, which initially resolves are still
      at risk for an atypical form of chronic lung disease. The prolonged respiratory
      support they require as a result of this type of lung disease increases their
      risk for complications of prematurity, which may outlast their lung disease. We
      speculate that inflammation secondary to infection acquired shortly after birth
      may be an important step in the pathogenesis of ACLD.

PMID- 18059467
TI  - Demographic and nutritional factors associated with prolonged cholestatic
      jaundice in the premature infant.
AB  - OBJECTIVE: The primary aim of this study was to determine if an association
      exists between amino-acid levels and development of cholestasis. The secondary
      aim of our amino-acid dose comparison trial was to identify factors associated
      with the development of prolonged cholestatic jaundice. STUDY DESIGN: We compared
      demographic characteristics and amino-acid levels in neonates who developed
      cholestasis with those who did not. Parenteral-associated cholestatic liver
      disease was defined as a direct serum bilirubin above 5 mg per 100 ml any time
      during the first 28 days after birth in neonates with no history of biliary
      atresia or viral hepatitis. We obtained filter paper blood spots for amino acid
      and acylcarnitine measurements on the day of randomization and days 7 and 28 of
      age to identify a profile of values that could be used to identify neonates with
      evidence of abnormal liver function. RESULT: We enrolled 122 neonates in our
      study; 13 (10.7%) developed cholestasis. Neonates who developed cholestasis were
      more immature, had lower birth weight, were exposed to parenteral nutrition for a
      longer period, had a higher cumulative dose of amino acids, were less often on
      enteral nutrition by day 7 of age, more often had a patent ductus arteriosus and
      severe intraventricular hemorrhage and were more commonly treated with steroids
      by 28 days of age. Amino acid and acylcarnitine values were not different for the
      two groups on the day of randomization. On day 7 (parenteral phase of nutrition),
      blood urea nitrogen, citrulline, histidine, methionine and succinyl carnitine
      were higher, and serine, glutamate and thyroxine levels were lower in the
      neonates who developed cholestasis than in who did not. CONCLUSION: Cholestasis
      remains an important complication of parenteral nutrition, and several clinical
      and biochemical factors may be helpful in identifying high-risk patients.

PMID- 18059468
TI  - Family-based association study of cytotoxic T-lymphocyte antigen-4 with
      susceptibility to Graves' disease in Han population of Taiwan.
AB  - Graves' disease (GD) is a common organ-specific autoimmune disorder inherited as
      a complex trait. Although there has not been consensus regarding the genuine
      susceptibility alleles, many population-based genetic studies showed association
      of the cytotoxic T-lymphocyte antigen-4 (CTLA4) gene with GD. In contrast,
      evidence utilizing family-based studies came only from the Caucasian population.
      Here we performed a family-based association study in the Han population in
      Taiwan. We enrolled 374 affected individuals and 347 unaffected family members in
      151 GD pedigrees. Four single-nucleotide polymorphisms (SNP) and a short tandem
      repeat polymorphism (STRP) at CTLA4 were genotyped. Association of GD with a
      novel risk SNP at the 5' upstream region, CTLA4_-1722_T/C (rs733618), was
      demonstrated (P=0.0096). We also replicated the association signal of a coding
      SNP, CTLA4_+49_G/A (rs231775, P=0.0219). A common haplotype composed of CTLA4_
      1722_T/C and CTLA4_(AT)n (an STRP marker: UniSTS:48500) showed protective effect
      (P=0.0004). Our results of family-based association study, taken together with
      those from the Caucasian population, provide evidence that CTLA4 confers
      susceptibility to GD across different ethnic backgrounds.

PMID- 18059470
TI  - p166, a link between the trypanosome mitochondrial DNA and flagellum, mediates
      genome segregation.
AB  - Kinetoplast DNA (kDNA), the trypanosome mitochondrial genome, is a giant network
      containing several thousand interlocked DNA rings. Within the mitochondrion, kDNA
      is condensed into a disk-shaped structure positioned near the flagellar basal
      body. The disk is linked to the basal body by a remarkable transmembrane filament
      system named the tripartite attachment complex (TAC). Following kDNA replication,
      the TAC mediates network segregation, pulling the progeny networks into the
      daughter cells by their linkage to the basal bodies. So far TAC has been
      characterized only morphologically with no known protein components. By screening
      an RNAi library, we discovered p166, a protein localizing between the kDNA and
      basal body in intact cells and in isolated flagellum-kDNA complexes. RNAi of p166
      has only small effects on kDNA replication, but it causes profound defects in
      network segregation. For example, kDNA replication without segregation causes the
      networks to grow to enormous size. Thus, p166 is the first reported molecular
      component of the TAC, and its discovery will facilitate study of kDNA segregation
      machinery at the molecular level.

PMID- 18059471
TI  - 14-3-3 proteins recognize a histone code at histone H3 and are required for
      transcriptional activation.
AB  - Interphase phosphorylation of S10 at histone H3 is linked to transcriptional
      activation of a specific subset of mammalian genes like HDAC1. Recently, 14-3-3
      proteins have been described as detectors for this phosphorylated histone H3
      form. Here, we report that 14-3-3 binding is modulated by combinatorial
      modifications of histone H3. S10 phosphorylation is necessary for an interaction,
      but additional H3K9 or H3K14 acetylation increases the affinity of 14-3-3 for
      histone H3. Histone H3 phosphoacetylation occurs concomitant with K9 methylation
      in vivo, suggesting that histone phosphorylation and acetylation can synergize to
      overcome repressive histone methylation. Chromatin immunoprecipitation
      experiments reveal recruitment of 14-3-3 proteins to the HDAC1 gene in an H3S10ph
      dependent manner. Recruitment of 14-3-3 to the promoter is enhanced by additional
      histone H3 acetylation and correlates with dissociation of the repressive binding
      module HP1gamma. Finally, siRNA-mediated loss of 14-3-3 proteins abolishes the
      transcriptional activation of HDAC1. Together our data indicate that 14-3-3
      proteins are crucial mediators of histone phosphoacetylation signals.

PMID- 18059472
TI  - Lipids revert inert Abeta amyloid fibrils to neurotoxic protofibrils that affect
      learning in mice.
AB  - Although soluble oligomeric and protofibrillar assemblies of Abeta-amyloid
      peptide cause synaptotoxicity and potentially contribute to Alzheimer's disease
      (AD), the role of mature Abeta-fibrils in the amyloid plaques remains
      controversial. A widely held view in the field suggests that the fibrillization
      reaction proceeds 'forward' in a near-irreversible manner from the monomeric
      Abeta peptide through toxic protofibrillar intermediates, which subsequently
      mature into biologically inert amyloid fibrils that are found in plaques. Here,
      we show that natural lipids destabilize and rapidly resolubilize mature Abeta
      amyloid fibers. Interestingly, the equilibrium is not reversed toward monomeric
      Abeta but rather toward soluble amyloid protofibrils. We characterized these
      'backward' Abeta protofibrils generated from mature Abeta fibers and compared
      them with previously identified 'forward' Abeta protofibrils obtained from the
      aggregation of fresh Abeta monomers. We find that backward protofibrils are
      biochemically and biophysically very similar to forward protofibrils: they
      consist of a wide range of molecular masses, are toxic to primary neurons and
      cause memory impairment and tau phosphorylation in mouse. In addition, they
      diffuse rapidly through the brain into areas relevant to AD. Our findings imply
      that amyloid plaques are potentially major sources of soluble toxic Abeta
      aggregates that could readily be activated by exposure to biological lipids.

PMID- 18059473
TI  - Parallel topology of genetically fused EmrE homodimers.
AB  - EmrE is a small H+-coupled multidrug transporter in Escherichia coli. Claims have
      been made for an antiparallel topology of this homodimeric protein. However, our
      own biochemical studies performed with detergent-solubilized purified protein
      support a parallel topology of the protomers. We developed an alternative
      approach to constrain the relative topology of the protomers within the dimer so
      that their activity can be assayed also in vivo before biochemical handling.
      Tandem EmrE was built with two identical monomers genetically fused tail to head
      (C-terminus of the first to N-terminus of the second monomer) with hydrophilic
      linkers of varying length. All the constructs conferred resistance to ethidium by
      actively removing it from the cytoplasm. The purified proteins bound substrate
      and transported methyl viologen into proteoliposomes by a proton-dependent
      mechanism. A tandem where one of the essential glutamates was replaced with
      glutamine transported only monovalent substrates and displayed a modified
      stoichiometry. The results support a parallel topology of the protomers in the
      functional dimer. The implications regarding insertion and evolution of membrane
      proteins are discussed.

PMID- 18059474
TI  - Impaired liver regeneration in Nrf2 knockout mice: role of ROS-mediated
      insulin/IGF-1 resistance.
AB  - The liver is frequently challenged by surgery-induced metabolic overload, viruses
      or toxins, which induce the formation of reactive oxygen species. To determine
      the effect of oxidative stress on liver regeneration and to identify the
      underlying signaling pathways, we studied liver repair in mice lacking the Nrf2
      transcription factor. In these animals, expression of several cytoprotective
      enzymes was reduced in hepatocytes, resulting in oxidative stress. After partial
      hepatectomy, liver regeneration was significantly delayed. Using in vitro and in
      vivo studies, we identified oxidative stress-mediated insulin/insulin-like growth
      factor resistance as an underlying mechanism. This deficiency impaired the
      activation of p38 mitogen-activated kinase, Akt kinase and downstream targets
      after hepatectomy, resulting in enhanced death and delayed proliferation of
      hepatocytes. Our results reveal novel roles of Nrf2 in the regulation of growth
      factor signaling and in tissue repair. In addition, they provide new insight into
      the mechanisms underlying oxidative stress-induced defects in liver regeneration.
      These findings may provide the basis for the development of new strategies to
      improve regeneration in patients with acute or chronic liver damage.

PMID- 18059475
TI  - Cdc2p controls the forkhead transcription factor Fkh2p by phosphorylation during
      sexual differentiation in fission yeast.
AB  - In most eukaryotes, cyclin-dependent kinases (Cdks) play a central role in
      control of cell-cycle progression. Cdks are inactivated from the end of mitosis
      to the start of the next cell cycle as well as during sexual differentiation. The
      forkhead-type transcription factor Fkh2p is required for the periodic expression
      of many genes and for efficient mating in the fission yeast Schizosaccharomyces
      pombe. However, the mechanism responsible for coordination of cell-cycle
      progression with sexual differentiation is still unknown. We now show that Fkh2p
      is phosphorylated by Cdc2p (Cdk1) and that phosphorylation of Fkh2p on T314 or
      S462 by this Cdk blocks mating in S. pombe by preventing the induction of ste11+
      transcription, which is required for the onset of sexual development. We propose
      that functional interaction between Cdks and forkhead transcription factors may
      link the mitotic cell cycle and sexual differentiation.

PMID- 18059476
TI  - RSC regulates nucleosome positioning at Pol II genes and density at Pol III
      genes.
AB  - Nucleosomes can restrict the access of transcription factors to chromatin. RSC is
      a SWI/SNF-family chromatin-remodeling complex from yeast that repositions and
      ejects nucleosomes in vitro. Here, we examined these activities and their
      importance in vivo. We utilized array-based methods to examine nucleosome
      occupancy and positioning at more than 200 locations in the genome following the
      controlled destruction of the catalytic subunit of RSC, Sth1. Loss of RSC
      function caused pronounced and general reductions in new transcription from Pol
      I, II, and III genes. At Pol III genes, Sth1 loss conferred a general reduction
      in RNA Pol III occupancy and a gain in nucleosome density. Notably at the one Pol
      III gene examined, histone restoration was partly replication-dependent. In
      contrast, at Pol II promoters we observed primarily single nucleosome changes,
      including movement. Importantly, alterations near the transcription start site
      were more common at RSC-occupied promoters than at non-occupied promoters. Thus,
      RSC action affects both nucleosome density and positioning in vivo, but applies
      these remodeling modes differently at Pol II and Pol III genes.

PMID- 18059477
TI  - Molecular basis of the C-terminal tail-to-tail assembly of the sarcomeric
      filament protein myomesin.
AB  - Sarcomeric filament proteins display extraordinary properties in terms of protein
      length and mechanical elasticity, requiring specific anchoring and assembly
      mechanisms. To establish the molecular basis of terminal filament assembly, we
      have selected the sarcomeric M-band protein myomesin as a prototypic filament
      model. The crystal structure of the myomesin C-terminus, comprising a tandem
      array of two immunoglobulin (Ig) domains My12 and My13, reveals a dimeric end-to
      end filament of 14.3 nm length. Although the two domains share the same fold, an
      unexpected rearrangement of one beta-strand reveals how they are evolved into
      unrelated functions, terminal filament assembly (My13) and filament propagation
      (My12). The two domains are connected by a six-turn alpha-helix, of which two
      turns are void of any interactions with other protein parts. Thus, the overall
      structure of the assembled myomesin C-terminus resembles a three-body beads-on
      the-string model with potentially elastic properties. We predict that the found
      My12-helix-My13 domain topology may provide a structural template for the
      filament architecture of the entire C-terminal Ig domain array My9-My13 of
      myomesin.

PMID- 18059479
TI  - Sirolimus enhances the effect of apoptotic cell infusion on hematopoietic
      engraftment and tolerance induction.

PMID- 18059480
TI  - Myeloid leukemia in children 4 years or older with Down syndrome often lacks
      GATA1 mutation and cytogenetics and risk of relapse are more akin to sporadic
      AML.

PMID- 18059478
TI  - Dimerization of FIR upon FUSE DNA binding suggests a mechanism of c-myc
      inhibition.
AB  - c-myc is essential for cell homeostasis and growth but lethal if improperly
      regulated. Transcription of this oncogene is governed by the counterbalancing
      forces of two proteins on TFIIH--the FUSE binding protein (FBP) and the FBP
      interacting repressor (FIR). FBP and FIR recognize single-stranded DNA upstream
      of the P1 promoter, known as FUSE, and influence transcription by oppositely
      regulating TFIIH at the promoter site. Size exclusion chromatography coupled with
      light scattering reveals that an FIR dimer binds one molecule of single-stranded
      DNA. The crystal structure confirms that FIR binds FUSE as a dimer, and only the
      N-terminal RRM domain participates in nucleic acid recognition. Site-directed
      mutations of conserved residues in the first RRM domain reduce FIR's affinity for
      FUSE, while analogous mutations in the second RRM domain either destabilize the
      protein or have no effect on DNA binding. Oppositely oriented DNA on parallel
      binding sites of the FIR dimer results in spooling of a single strand of bound
      DNA, and suggests a mechanism for c-myc transcriptional control.

PMID- 18059481
TI  - Subcellular distribution of p210(BCR-ABL) in CML cell lines and primary CD34+ CML
      cells.
AB  - We analysed the subcellular distribution of p210(BCR-ABL) protein using a
      junction-specific anti-BCR-ABL monoclonal antibody and confocal laser scanning
      microscopy (CLSM). Our studies have shown that p210(BCR-ABL) is arranged in
      discrete foci in the cytoplasm of cell lines and primary CD34(+) cells but not
      mononuclear cells suggesting the foci may be a feature of immature chronic
      myeloid leukaemia cells. We have devised a strategy to score the foci and found
      the mean number of foci varies between the cell types. The number of foci per
      cell is directly related to the level of p210(BCR-ABL) expression. CLSM was also
      used to analyse the distribution and colocalization of CT10 regulator-like (CRKL)
      p210(BCR-ABL). CRKL-p210(BCR-ABL) foci were completely or partially associated,
      touching or separate in different regions of the same cell. We also analysed the
      distribution of phosphorylated CRKL (pCRKL) with p210(BCR-ABL) and unexpectedly
      found only a small proportion of pCRKL in complex with p210(BCR-ABL). The foci
      distribution and high levels of uncomplexed p210(BCR-ABL), pCRKL and CRKL protein
      suggested the possibility of a dynamic equilibrium. Imatinib promoted nuclear
      transport of p210(BCR-ABL)-positive foci. It also disrupted complex formation
      between p210(BCR-ABL) and casitas B-cell lymphoma and CRKL but not between
      p210(BCR-ABL) and GRB2. Our observations of the CRKL and p210(BCR-ABL) complex
      may be important for understanding the function of CRKL.

PMID- 18059482
TI  - Base excision repair dysfunction in a subgroup of patients with myelodysplastic
      syndrome.
AB  - In myelodysplastic syndromes (MDS) increased chromosomal breaks point toward
      defects in DNA repair machinery including base excision repair (BER) pathway
      involved in handling of oxidative DNA damage. We investigated whether defects in
      this pathway can be found in MDS. Elevated levels of 8-oxoguanine (8-OG) were
      found in a significant proportion of MDS patients, indicating increased oxidative
      DNA damage or defective handling of oxidative load. In a distinct subgroup of
      patients, increased 8-OG content was associated with increased hOGG1 mRNA
      expression and activity. In some patients, increased numbers of abasic sites (AP
      sites) correlated with low levels of POLbeta. To further investigate the nature
      of this defect, we examined genetic lesions potentially explaining accumulation
      of 8-OG and AP sites. We genotyped a large cohort of MDS patients and found a
      correlation between increased oxidative damage and the presence of the hOGG1
      Cys326 allele suggesting inadequate compensatory feedback. Overall, this hOGG1
      variant was more frequent in MDS, particularly in advanced forms, as compared to
      controls. In summary, we demonstrated that BER dysfunction in some MDS patients
      may be responsible for the increased 8-OG incorporation and explains one aspect
      of the propensity to chromosomal breaks in MDS but other mechanisms may also be
      involved.

PMID- 18059483
TI  - Prognostic interaction between thrombocytosis and JAK2 V617F mutation in the WHO
      subcategories of myelodysplastic/myeloproliferative disease-unclassifiable and
      refractory anemia with ringed sideroblasts and marked thrombocytosis.

PMID- 18059485
TI  - In human genome, generation of a nuclear export signal through duplication
      appears unique to nucleophosmin (NPM1) mutations and is restricted to AML.

PMID- 18059484
TI  - HLA-G turns off erythropoietin receptor signaling through JAK2 and JAK2 V617F
      dephosphorylation: clinical relevance in polycythemia vera.
AB  - HLA-G5 is secreted by erythroblasts in all hematopoietic organs, suggesting a
      role for this protein in erythropoiesis. To examine this, we analyzed whether HLA
      G5 affects the proliferation of UT7/EPO and HEL erythroleukemia cells and
      characterized the mechanism by which HLA-G5 influences erythropoietin receptor
      (EPOR) signaling. We show that HLA-G5 inhibits the proliferation of UT7/EPO
      cells, the EPOR signaling of which is similar to that of normal erythroid
      progenitors. HLA-G5-mediated inhibition was associated with reduced
      phosphorylation of JAK2 kinase and that of the downstream signaling proteins STAT
      5 and STAT-3. Involvement of JAK2 in erythroid cell proliferation has been
      highlighted by the role of JAK2 V617F mutation in polycythemia vera (PV), a
      myeloproliferative disorder characterized by erythroid lineage overproduction. We
      demonstrate that HLA-G5 downregulates EPOR constitutive signaling of JAK2 V617F
      expressing HEL cells, leading to inhibition of cell proliferation through G1 cell
      cycle arrest. Combination of HLA-G5 with JAK inhibitor I further decreases HEL
      cell growth. Clinical relevance is provided by analysis of PV patients who carry
      JAK2 V617F mutation, showing that HLA-G5 inhibits the formation of erythropoietin
      independent erythroid colonies. Such HLA-G5-mediated inhibition constitutes a new
      parameter to be considered in the design of future approaches aimed at treating
      JAK2 V617F-positive myeloproliferative disorders.

PMID- 18059486
TI  - Nonmonoclonal PTCH gene mutations in psoralen plus UVA-associated basal cell
      carcinomas.

PMID- 18059487
TI  - UVB-induced activation of NF-kappaB is regulated by the IGF-1R and dependent on
      p38 MAPK.
AB  - To manage the frequent exposure to carcinogenic UVB wavelengths found in
      sunlight, keratinocytes have extensive protective measures to handle UVB-induced
      DNA damage. Recent in vitro evidence and epidemiological data suggest that one
      possible protective mechanism is dependent on the functional status of the IGF-1R
      signaling network. A second important signaling pathway regulating the response
      of keratinocytes to UVB involves the activation of the NF-kappaB transcription
      factor. Although it is clear that proper functioning of both the IGF-1R and NF
      kappaB signaling networks are critical for the appropriate response of
      keratinocytes to UVB irradiation, it is currently uncertain if these two pathways
      interact. We now demonstrate that the activation of the NF-kappaB transcription
      factor by UVB is altered by the functional status of the IGF-1R. In the absence
      of ligand-activated IGF-1R, UVB-induced NF-kappaB consisted primarily of p50:p50
      homodimers. Furthermore, the p38 kinase MAPK directs the subunit composition of
      NF-kappaB following UVB irradiation, most likely in an IGF-1R-dependent manner.
      We hypothesize that UVB irradiation leads to an activated p38 MAPK that is
      regulated in an IGF-1R-dependent manner, leading to NF-kappaB p50:RelA/p65
      activation and a survival phenotype. In the absence of ligand-activated IGF-1R,
      UVB irradiation leads to the induction of NF-kappaB p50:p50 homodimers and a p38
      dependent increased susceptibility to apoptosis.

PMID- 18059488
TI  - Bacteria are not the primary cause of bleaching in the Mediterranean coral
      Oculina patagonica.
AB  - Coral bleaching occurs when the endosymbiosis between corals and their symbionts
      disintegrates during stress. Mass coral bleaching events have increased over the
      past 20 years and are directly correlated with periods of warm sea temperatures.
      However, some hypotheses have suggested that reef-building corals bleach due to
      infection by bacterial pathogens. The 'Bacterial Bleaching' hypothesis is based
      on laboratory studies of the Mediterranean invading coral, Oculina patagonica,
      and has further generated conclusions such as the coral probiotic hypothesis and
      coral hologenome theory of evolution. We aimed to investigate the natural
      microbial ecology of O. patagonica during the annual bleaching using fluorescence
      in situ hybridization to map bacterial populations within the coral tissue
      layers, and found that the coral bleaches on the temperate rocky reefs of the
      Israeli coastline without the presence of Vibrio shiloi or bacterial penetration
      of its tissue layers. Bacterial communities were found associated with the
      endolithic layer of bleached coral regions, and a community dominance shift from
      an apparent cyanobacterial-dominated endolithic layer to an algal-dominated layer
      was found in bleached coral samples. While bacterial communities certainly play
      important roles in coral stasis and health, we suggest environmental stressors,
      such as those documented with reef-building corals, are the primary triggers
      leading to bleaching of O. patagonica and suggest that bacterial involvement in
      patterns of bleaching is that of opportunistic colonization.

PMID- 18059489
TI  - Presence of two Lactobacillus and Bifidobacterium probiotic strains in the
      neonatal ileum.
AB  - The overall purpose of this study was to examine the lactobacilli and
      bifidobacteria microbiota in the human ileum at a very early stage of life.
      Ileostomy effluents from two infants, taken at different time points, were plated
      on Lactobacillus selective agar and cys-MRS containing mupirocin to select for
      bifidobacteria. In one case, a stool sample following ileostomy reversal was
      subsequently analyzed microbiologically. Pulse-field gel electrophoresis and 16S
      rRNA sequencing was used to investigate the cultivable population of
      bifidobacteria and lactobacilli and denaturing gradient gel electrophoresis
      (DGGE) to examine the non-cultivable population. The probiotic strain,
      Lactobacillus paracasei NFBC 338, was recovered at both time points from one of
      the infants and dominated in the small intestine for a period of over 3 weeks.
      Moreover, the probiotic strain, B. animalis subsp. lactis Bb12, was obtained from
      the other infant. This study shows the presence of two known probiotic strains in
      the upper intestinal tract at an early stage of human life and thus provides some
      evidence for their ability to colonize the infant small intestine.

PMID- 18059490
TI  - Changes in coral-associated microbial communities during a bleaching event.
AB  - Environmental stressors such as increased sea surface temperatures are well-known
      for contributing to coral bleaching; however, the effect of increased
      temperatures and subsequent bleaching on coral-associated microbial communities
      is poorly understood. Colonies of the hard coral Acropora millepora were tagged
      on a reef flat off Magnetic Island (Great Barrier Reef) and surveyed over 2.5
      years, which included a severe bleaching event in January/February 2002. Daily
      average water temperatures exceeded the previous 10-year average by more than 1
      degrees C for extended periods with field-based visual surveys recording all
      tagged colonies displaying signs of bleaching. During the bleaching period,
      direct counts of coral zooxanthellae densities decreased by approximately 64%,
      before recovery to pre-bleaching levels after the thermal stress event. A subset
      of three tagged coral colonies were sampled through the bleaching event and
      changes in the microbial community elucidated. Denaturing gradient gel
      electrophoresis (DGGE) analysis demonstrated conserved bacterial banding profiles
      between the three coral colonies, confirming previous studies highlighting
      specific microbial associations. As coral colonies bleached, the microbial
      community shifted and redundancy analysis (RDA) of DGGE banding patterns revealed
      a correlation of increasing temperature with the appearance of Vibrio-affiliated
      sequences. Interestingly, this shift to a Vibrio-dominated community commenced
      prior to visual signs of bleaching. Clone libraries hybridized with Vibrio
      specific oligonucleotide probes confirmed an increase in the fraction of Vibrio
      affiliated clones during the bleaching period. Post bleaching, the coral
      microbial associations again shifted, returning to a profile similar to the
      fingerprints prior to bleaching. This provided further evidence for corals
      selecting and shaping their microbial partners. For non-bleached samples, a close
      association with Spongiobacter-related sequences were revealed by both clone
      libraries and DGGE profiling. Despite Vibrio species being previously implicated
      in bleaching of specific coral species, it is unsure if the relative increase in
      retrieved Vibrio sequences is due to bacterial infection or an opportunistic
      response to compromised health and changing environmental parameters of the coral
      host. This study provides the first molecular-based study demonstrating changes
      in coral-associated bacterial assemblages during a bleaching event on a natural
      reef system.

PMID- 18059492
TI  - Streptococcus pyogenes serotype-dependent and independent changes in infected HEp
      2 epithelial cells.
AB  - The adherence, internalization and persistence of the human pathogen
      Streptococcus pyogenes (group A streptococci, GAS) to and within host cells were
      studied, and the induced responses of the infected epithelial cells were
      investigated. Next to common cellular responses on GAS infection, many responses
      of the infected HEp-2 epithelial cells are GAS serotype-specific. Moreover,
      several cellular responses do not correlate with the actual bacterial numbers
      adherent, internalized and persistent within the cells or the production of major
      cytolysins, as demonstrated for cytoskeletal pathways, cytokine release and
      apoptosis induction in infected cells. Measurement of activated caspases and
      caspase inhibition experiments uncovered activation of multiple caspase pathways
      by all GAS serotypes tested (M1, M3, M6 and M18). However, caspase 9 played a
      central role for M6 infections. During the persistence phase of the interaction,
      a differential and dynamic behavior of the infecting GAS serotype strains was
      found. After 14 h of host cell contact, all serotype strains caused host cell
      damage by virtually equal portions of apoptosis induction and necrosis
      mechanisms, as revealed by measurements of CK18Asp396/CK18 ratios. Between 14 and
      24 h, persisting serotype M1 bacteria pertained this effect, whereas the serotype
      M6 GAS strain induced a major shift to necrotic mechanisms, and the serotype M3
      and M18 GAS strains stimulated less necrosis, but shifted their host cells to
      apoptosis induction. Together, our study revealed that many cellular responses do
      not belong to general and uniform pathways, which are exploited by all GAS
      serotypes, explaining many of the already published discordant results.

PMID- 18059493
TI  - Localization of 'Candidatus Endobugula sertula' and the bryostatins throughout
      the life cycle of the bryozoan Bugula neritina.
AB  - 'Candidatus Endobugula sertula,' the uncultivated gamma-proteobacterial symbiont
      of the marine bryozoan Bugula neritina, synthesizes bryostatins, complex
      polyketides that render B. neritina larvae unpalatable to predators. Although the
      symbiosis is well described, little is known about the locations of 'E. sertula'
      or the bryostatins throughout larval settlement, metamorphosis and early
      development. In this study, we simultaneously localized 'E. sertula' and the
      bryostatins in multiple stages of the B. neritina life cycle, using a novel
      bryostatin detection method based on its known ability to bind mammalian protein
      kinase C. Our results suggest that the bryostatins are deposited onto the
      exterior of B. neritina larvae during embryonic development, persist on the
      larval surface throughout metamorphosis and are shed prior to cuticle formation.
      During metamorphosis, 'E. sertula' remains adhered to the larval pallial
      epithelium and is incorporated into the preancestrula cystid tissue layer, which
      ultimately develops into a bud and gives rise to the next zooid in the colony.
      Colocalization of bryostatin signal with aggregates of 'E. sertula' in buds of
      ancestrulae suggested new synthesis of bryostatins in ancestrulae. In adult B.
      neritina colonies, symbiont microcolonies were observed in the funicular cords of
      rhizoids, which likely result in asexual transmission of 'E. sertula' to
      regenerated colonies. Furthermore, bryostatin signal was detected on the surface
      of the rhizoids of adult B. neritina colonies. Through simultaneous localization
      of the bryostatins and the 'E. sertula,' we determined how 'E. sertula' is
      transmitted, and identified shifts in bryostatin localization throughout the life
      cycle of the host B. neritina.

PMID- 18059494
TI  - Population level functional diversity in a microbial community revealed by
      comparative genomic and metagenomic analyses.
AB  - In microbial mat communities of Yellowstone hot springs, ribosomal RNA (rRNA)
      sequence diversity patterns indicate the presence of closely related bacterial
      populations along environmental gradients of temperature and light. To identify
      the functional bases for adaptation, we sequenced the genomes of two
      cyanobacterial (Synechococcus OS-A and OS-B') isolates representing ecologically
      distinct populations that dominate at different temperatures and are major
      primary producers in the mat. There was a marked lack of conserved large-scale
      gene order between the two Synechococcus genomes, indicative of extensive genomic
      rearrangements. Comparative genomic analyses showed that the isolates shared a
      large fraction of their gene content at high identity, yet, differences in
      phosphate and nitrogen utilization pathways indicated that they have adapted
      differentially to nutrient fluxes, possibly by the acquisition of genes by
      lateral gene transfer or their loss in certain populations. Comparisons of the
      Synechococcus genomes to metagenomic sequences derived from mats where these
      Synechococcus stains were originally isolated, revealed new facets of microbial
      diversity. First, Synechococcus populations at the lower temperature regions of
      the mat showed greater sequence diversity than those at high temperatures,
      consistent with a greater number of ecologically distinct populations at the
      lower temperature. Second, we found evidence of a specialized population that is
      apparently very closely related to Synechococcus OS-B', but contains genes that
      function in the uptake of reduced ferrous iron. In situ expression studies
      demonstrated that these genes are differentially expressed over the diel cycle,
      with highest expression when the mats are anoxic and iron may be in the reduced
      state. Genomic information from these mat-specific isolates and metagenomic
      information can be coupled to detect naturally occurring populations that are
      associated with different functionalities, not always represented by isolates,
      but which may nevertheless be important for niche partitioning and the
      establishment of microbial community structure.

PMID- 18059495
TI  - Correlation of patterns of denitrification instability in replicated bioreactor
      communities with shifts in the relative abundance and the denitrification
      patterns of specific populations.
AB  - To assess the effects of community structure on the stability of denitrification,
      six chemostat cultures derived from the same denitrifying community were
      subjected to step increases in feed nitrate concentration and monitored for
      evidence that denitrification was either not occurring (indicated by the presence
      of nitrate) or was incomplete (indicated by the presence of nitrite or nitrous
      oxide). Functional stability was defined and quantified from the pattern of
      effluent concentration trends of nitrate and denitrification intermediates.
      Microbial community structure and dynamics were analyzed by terminal restriction
      fragment length polymorphism analysis of the 16S rRNA gene. Functional stability
      varied: one chemostat community lost the ability to reduce all of the influent
      nitrate; others continued to reduce all of the influent nitrate, but accumulated
      varying amounts of nitrous oxide. The microbial community structure in two of the
      chemostats diverged from the others, and variation of functional response among
      chemostats corresponded with the divergence of community structure. The
      Acidovorax-like terminal restriction fragment (T-RF) dominated the chemostat that
      accumulated nitrate, and an Acidovorax-like isolate reduced nitrate directly to
      dinitrogen gas in batch nitrate reduction assays. In the nitrous oxide
      accumulating chemostats, the relative abundance of the Pseudomonas-like T-RF was
      strongly and significantly correlated with the magnitude of nitrous oxide
      accumulation, and a Pseudomonas-like isolate accumulated nitrous oxide in batch
      assays.

PMID- 18059496
TI  - Organic substrate quality as the link between bacterioplankton carbon demand and
      growth efficiency in a temperate salt-marsh estuary.
AB  - Bacterioplankton communities play a key role in aquatic carbon cycling,
      specifically with respect to the magnitude of organic carbon processed and
      partitioning of this carbon into biomass and respiratory losses. Studies of
      bacterioplankton carbon demand (BCD) and growth efficiency (BGE) frequently
      report higher values in more productive systems, suggesting these aspects of
      carbon metabolism may be positively coupled. However, the existence of such a
      relationship in natural aquatic systems has yet to be identified. Using a
      comprehensive 2-year study of bacterioplankton carbon metabolism in a temperate
      estuary, we investigated BCD and BGE and explored factors that may modulate their
      magnitude and coherence, including nutrient concentrations, dissolved nutrient
      uptake and source and quality of dissolved organic carbon (DOC). During the
      course of our study, BCD ranged from 0.4 to 15.9 microg l(-1) h(-1), with an
      overall mean of 3.8 microg l(-1) h(-1). Mean BGE was similar to that reported for
      other estuarine systems (0.32) and of comparable range (that is, 0.06-0.68).
      Initial analyses identified a negative correlation between BCD and BGE, yet
      removal of the effect of temperature revealed an underlying positive coupling
      that was also correlated with long-term DOC lability. Whereas BCD was weakly
      related to ambient DOC concentrations, neither BCD nor BGE showed any
      relationship with ambient nutrient concentrations or nutrient uptake
      stoichiometries. We conclude that in this carbon-rich estuary, organic matter
      source and quality play an important role in regulating the magnitude of carbon
      metabolism and may be more important than nutrient availability alone in the
      regulation of BGE.

PMID- 18059491
TI  - Subsurface clade of Geobacteraceae that predominates in a diversity of Fe(III)
      reducing subsurface environments.
AB  - There are distinct differences in the physiology of Geobacter species available
      in pure culture. Therefore, to understand the ecology of Geobacter species in
      subsurface environments, it is important to know which species predominate. Clone
      libraries were assembled with 16S rRNA genes and transcripts amplified from three
      subsurface environments in which Geobacter species are known to be important
      members of the microbial community: (1) a uranium-contaminated aquifer located in
      Rifle, CO, USA undergoing in situ bioremediation; (2) an acetate-impacted aquifer
      that serves as an analog for the long-term acetate amendments proposed for in
      situ uranium bioremediation and (3) a petroleum-contaminated aquifer in which
      Geobacter species play a role in the oxidation of aromatic hydrocarbons coupled
      with the reduction of Fe(III). The majority of Geobacteraceae 16S rRNA sequences
      found in these environments clustered in a phylogenetically coherent subsurface
      clade, which also contains a number of Geobacter species isolated from subsurface
      environments. Concatamers constructed with 43 Geobacter genes amplified from
      these sites also clustered within this subsurface clade. 16S rRNA transcript and
      gene sequences in the sediments and groundwater at the Rifle site were highly
      similar, suggesting that sampling groundwater via monitoring wells can recover
      the most active Geobacter species. These results suggest that further study of
      Geobacter species in the subsurface clade is necessary to accurately model the
      behavior of Geobacter species during subsurface bioremediation of metal and
      organic contaminants.

PMID- 18059497
TI  - Primary producing prokaryotic communities of brine, interface and seawater above
      the halocline of deep anoxic lake L'Atalante, Eastern Mediterranean Sea.
AB  - Meso- and bathypelagic ecosystems represent the most common marine ecological
      niche on Earth and contain complex communities of microorganisms that are for the
      most part ecophysiologically poorly characterized. Gradients of physico-chemical
      factors (for example, depth-related gradients of light, temperature, salinity,
      nutrients and pressure) constitute major forces shaping ecosystems at activity
      'hot spots' on the ocean floor, such as hydrothermal vents, cold seepages and mud
      volcanoes and hypersaline lakes, though the relationships between community
      composition, activities and environmental parameters remain largely elusive. We
      report here results of a detailed study of primary producing microbial
      communities in the deep Eastern Mediterranean Sea. The brine column of the deep
      anoxic hypersaline brine lake, L'Atalante, the overlying water column and the
      brine-seawater interface, were characterized physico- and geochemically, and
      microbiologically, in terms of their microbial community compositions, functional
      gene distributions and [(14)C]bicarbonate assimilation activities. The depth
      distribution of genes encoding the crenarchaeal ammonia monooxygenase alpha
      subunit (amoA), and the bacterial ribulose-1,5-biphosphate carboxylase/oxygenase
      large subunit (RuBisCO), was found to coincide with two different types of
      chemoautotrophy. Meso- and bathypelagic microbial communities were enriched in
      ammonia-oxidizing Crenarchaeota, whereas the autotrophic community at the
      oxic/anoxic interface of L'Atalante lake was dominated by Epsilonproteobacteria
      and sulfur-oxidizing Gammaproteobacteria. These autotrophic microbes are thus the
      basis of the food webs populating these deep-sea ecosystems.

PMID- 18059498
TI  - Fungal communities from methane hydrate-bearing deep-sea marine sediments in
      South China Sea.
AB  - To elucidate fungal diversity in methane hydrate-bearing deep-sea marine
      sediments in the South China Sea, internal transcribed spacer (ITS) regions of
      rRNA genes from five different sediment DNA samples were amplified and
      phylogenetically analyzed. Total five ITS libraries were constructed and 413
      clones selected randomly were grouped into 24 restriction patterns by Amplified
      Ribosomal DNA Restriction Analysis (ARDRA). ITS sequences of 44 representative
      clones were determined and compared with the GenBank database using gapped-BLAST.
      The phylogenetic analysis showed that the ITS sequences (71-97% similarity) were
      similar to those of Phoma, Lodderomyces, Malassezia, Cryptococcus,
      Cylindrocarpon, Hortaea, Pichia, Aspergillus and Candida. The remaining sequences
      were not associated to any known fungi or fungal sequences in the public
      database. The results suggested that methane hydrate-bearing deep-sea marine
      sediments harbor diverse fungi. This is the first report on fungal communities
      from methane hydrate-bearing deep-sea marine sediments in South China Sea.

PMID- 18059499
TI  - Soil fungal abundance and diversity: another victim of the invasive plant
      Centaurea maculosa.
AB  - Interactions between plants and soil microbes are important determinants of both
      above- and belowground community composition, and ultimately ecosystem function.
      As exotic plants continue to invade and modify native plant communities, there
      has been increasing interest in determining the influence of exotic invasives on
      native soil microbial communities. Here, using highly sensitive molecular
      techniques, we examine fungal abundance and diversity in the soil surrounding a
      particularly aggressive invasive plant species in North America, Centaurea
      maculosa Lam. In mixed stands, we show that this invasive weed can alter the
      native fungal community composition within its own rhizosphere and that of
      neighboring native plants. At higher densities, the effect of C. maculosa on
      native soil fungal communities was even greater. Our results demonstrate that
      this invasive weed can have significant effects not only on visible aboveground
      biodiversity but also on the native soil microbial community that extends beyond
      its rhizosphere.

PMID- 18059500
TI  - Role of the soluble guanylyl cyclase alpha1-subunit in mice corpus cavernosum
      smooth muscle relaxation.
AB  - Soluble guanylyl cyclase (sGC) is the major effector molecule for nitric oxide
      (NO) and as such an interesting therapeutic target for the treatment of erectile
      dysfunction. To assess the functional importance of the sGCalpha(1)beta(1)
      isoform in corpus cavernosum (CC) relaxation, CC from male sGCalpha(1)(-/-) and
      wild-type mice were mounted in organ baths for isometric tension recording. The
      relaxation to endogenous NO (from acetylcholine, bradykinin and electrical field
      stimulation) was nearly abolished in the sGCalpha(1)(-/-) CC. In the sGCalpha(1)(
      /-) mice, the relaxing influence of exogenous NO (from sodium nitroprusside and
      NO gas), BAY 41-2272 (NO-independent sGC stimulator) and T-1032
      (phosphodiesterase type 5 inhibitor) were also significantly decreased. The
      remaining exogenous NO-induced relaxation seen in the sGCalpha(1)(-/-) mice was
      significantly decreased by the sGC-inhibitor 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one. The specificity of the impairment of the sGC-related
      responses was demonstrated by the unaltered relaxations seen with forskolin
      (adenylyl cyclase activator) and 8-pCPT-cGMP (cGMP analog). In conclusion, the
      sGCalpha(1)beta(1) isoform is involved in corporal smooth muscle relaxation in
      response to NO and NO-independent sGC stimulators. The fact that there is still
      some effect of exogenous NO in the sGCalpha(1)(-/- mice suggests the contribution
      of (an) additional pathway(s).

PMID- 18059501
TI  - The application of quantitative methods for identifying and exploring the
      presence of bias in systematic reviews: PDE-5 inhibitors for erectile
      dysfunction.
AB  - A systematic review of PDE-5 inhibitors for erectile dysfunction was performed to
      evaluate the utility of quantitative methods for identifying and exploring the
      influence of bias and study quality on pooled outcomes from meta-analyses. We
      included 123 randomized controlled trials (RCTs). Methodological quality was
      poorly reported. All three drugs appeared highly effective. Indirect adjusted
      analyses showed no differences between the three drugs. Funnel plots and
      statistical tests showed no evidence of small-study effects for sildenafil
      whereas there was evidence of such bias for tadalafil and vardenafil. Adjustment
      for missing studies using trim and fill techniques did not alter the pooled
      estimates substantially. The exclusion of previous sildenafil nonresponders was
      associated with larger treatment effects for tadalafil. This investigation was
      hampered by poor reporting of methodological quality, a low number of studies,
      heterogeneity and large effect sizes. Despite such limitations, a comprehensive
      assessment of biases should be a routine in systematic reviews.

PMID- 18059502
TI  - Influence of PDE5 inhibitor on MRI measurement of clitoral volume response in
      women with FSAD: a feasibility study of a potential technique for evaluating drug
      response.
AB  - The purpose of this study was to determine if magnetic resonance imaging (MRI)
      could quantify a difference in clitoral response following administration of a
      vasoactive medication, in 12 women with female sexual arousal disorder (FSAD).
      Subjects were entered into a double-blind, randomized two-way crossover study of
      sildenafil 50 mg vs placebo administered 1 h prior to genital MRI. Each subject
      underwent two MR studies, performed while subjects viewed alternating segments of
      nonerotic and erotic video. MR images were analyzed for change in clitoral volume
      during each session. The mean change in clitoral volume for the entire group was
      higher in the sildenafil MRI session (1282 mm(3)) compared with placebo (849
      mm(3)) but did not reach statistical significance (P=0.064). Comparison using
      analysis of variance between the two sessions for each individual subject
      revealed a significant increase in clitoral volume following sildenafil compared
      with placebo in 6 of 12 subjects, no significant change in either imaging session
      in three subjects and in three subjects, there was a robust clitoral response in
      both MR sessions. In conclusion, MR measurements of clitoral volume can provide
      an objective measure of engorgement change following a vasoactive medication in
      women with FSAD.

PMID- 18059504
TI  - Combination of baculovirus-expressed BMP-2 and rotating-shaft bioreactor culture
      synergistically enhances cartilage formation.
AB  - Baculovirus is an emerging gene delivery vector, thanks to a number of unique
      advantages. Herein, we genetically modified the rabbit articular chondrocytes
      with a recombinant baculovirus (Bac-CB) encoding bone morphogenetic protein-2
      (BMP-2), which conferred high level BMP-2 expression and triggered the re
      differentiation of dedifferentiated third passage (P3) chondrocytes in the
      monolayer culture. The transduced and mock-transduced P3 cells were seeded into
      porous scaffolds and cultured in either the dishes or the rotating-shaft
      bioreactor (RSB), a novel bioreactor imparting a dynamic, two-phase culture
      environment. Neither mock-transduced constructs in the RSB culture nor the Bac-CB
      transduced constructs in the static culture grew into uniform cartilaginous
      tissues. Only the Bac-CB-transduced constructs cultured in the RSB for 3 weeks
      resulted in cartilaginous tissues with hyaline appearance, uniform cell
      distribution, cartilage-specific gene expression and considerably enhanced
      cartilage-specific extracellular matrix deposition, as determined by histological
      staining, reverse transcription-PCR analyses and biochemical assays. This is the
      first study demonstrating that combination of baculovirus-mediated growth factor
      expression and RSB culture synergistically enhanced in vitro creation of
      cartilaginous tissues from dedifferentiated chondrocytes. Since baculovirus
      transduction is generally considered safe, this approach represents a viable
      alternative to stimulate the formation of engineered cartilage in a more cost
      effective way than the growth factor supplementation.

PMID- 18059505
TI  - Human cytomegalovirus protein pp65: an efficient protein carrier system into
      human dendritic cells.
AB  - Protein-based immunogens are usually poor inducers of CD8(+) T cells. To enhance
      the induction of CD8(+) T cells, one approach is the use of protein immunogens
      coupled to protein transduction domains (PTDs). These are small cationic peptide
      sequences that significantly enhance the uptake of fused proteins into dendritic
      cells (DC) and then mediate their presentation in the context of major
      histocompatibility complex class I (MHC-I) and MHC-II molecules. One drawback of
      this system is the high concentrations of PTD-fusion proteins required. Here, we
      show that proteins fused to the human cytomegalovirus tegument protein pp65 were
      bound with higher efficiency to DCs than those fused to the described PTDs TatPTD
      and Penetratin. Furthermore, the fusion of pp65 to proteins led to an enhanced
      uptake of these proteins by DCs. Once taken up, CD4(+) and CD8(+) memory T cells
      were strongly stimulated ex vivo demonstrating that pp65 was efficiently
      processed and presented in the context of both MHC-I and MHC-II. These data make
      pp65 a promising delivery system to induce cellular immune responses by fused
      protein vaccines.

PMID- 18059506
TI  - Bevacizumab: the need for controlled studies to move forward.

PMID- 18059507
TI  - Our vision of vision health: the National Coalition for Vision Health.

PMID- 18059508
TI  - Hand washing in ophthalmology.

PMID- 18059510
TI  - Anticoagulant therapy after retinal vein occlusion in patients with protein S
      deficiency (Protein S deficiency with homozygous factor V Leiden mutation in
      central retinal vein occlusion. Vol. 42[4]).

PMID- 18059511
TI  - Cataract surgeons not balancing risks with benefits (Cataract wait-time
      benchmark: where do we go from here? Vol. 42[4]).

PMID- 18059514
TI  - Coats'-like retinitis pigmentosa variant and nanophthalmos.

PMID- 18059512
TI  - Managing Candida endophthalmitis (Recurrent Candida albicans endophthalmitis in
      an immunocompromised host. Vol. 42[1]).

PMID- 18059515
TI  - Surgical management of Centurion syndrome.

PMID- 18059516
TI  - Meesmann's corneal dystrophy managed with an epithelial delaminator.

PMID- 18059517
TI  - Alcohol as an alternative therapy in accommodative and convergence insufficiency.

PMID- 18059518
TI  - Acute angle-closure glaucoma in a teenage girl.

PMID- 18059519
TI  - Macular optical coherence tomography findings in progressive outer retinal
      necrosis.

PMID- 18059520
TI  - Iris atrophy in a patient with X-linked agammaglobulinemia.

PMID- 18059521
TI  - Ocular tobramycin-induced bronchospasm in an adult without asthma or atopy.

PMID- 18059522
TI  - Thelazia callipaeda in human vitreous.

PMID- 18059524
TI  - Acyl carrier protein: structure-function relationships in a conserved
      multifunctional protein family.
AB  - Acyl carrier protein (ACP) is a universal and highly conserved carrier of acyl
      intermediates during fatty acid synthesis. In yeast and mammals, ACP exists as a
      separate domain within a large multifunctional fatty acid synthase polyprotein
      (type I FAS), whereas it is a small monomeric protein in bacteria and plastids
      (type II FAS). Bacterial ACPs are also acyl donors for synthesis of a variety of
      products, including endotoxin and acylated homoserine lactones involved in quorum
      sensing; the distinct and essential nature of these processes in growth and
      pathogenesis make ACP-dependent enzymes attractive antimicrobial drug targets.
      Additionally, ACP homologues are key components in the production of secondary
      metabolites such as polyketides and nonribosomal peptides. Many ACPs exhibit
      characteristic structural features of natively unfolded proteins in vitro, with a
      dynamic and flexible conformation dominated by 3 parallel alpha helices that
      enclose the thioester-linked acyl group attached to a phosphopantetheine
      prosthetic group. ACP conformation may also be influenced by divalent cations and
      interaction with partner enzymes through its "recognition" helix II, properties
      that are key to its ability to alternately sequester acyl groups and deliver them
      to the active sites of ACP-dependent enzymes. This review highlights recent
      progress in defining how the structural features of ACP are related to its
      multiple carrier roles in fatty acid metabolism.

PMID- 18059525
TI  - Regulation of the cellular DNA double-strand break response.
AB  - DNA double-strand breaks occur frequently in cycling cells, and are also induced
      by exogenous sources, including ionizing radiation. Cells have developed
      integrated double-strand break response pathways to cope with these lesions,
      including pathways that initiate DNA repair (either via homologous recombination
      or nonhomologous end joining), the cell-cycle checkpoints (G1-S, intra-S phase,
      and G2-M) that provide time for repair, and apoptosis. However, before any of
      these pathways can be activated, the damage must first be recognized. In this
      review, we will discuss how the response of mammalian cells to DNA double-strand
      breaks is regulated, beginning with the activation of ATM, the pinnacle kinase of
      the double-strand break signalling cascade.

PMID- 18059526
TI  - Osmotic water permeability of rat intestinal brush border membrane vesicles:
      involvement of aquaporin-7 and aquaporin-8 and effect of metal ions.
AB  - Water channels AQP7 and AQP8 may be involved in transcellular water movement in
      the small intestine. We show that both AQP7 and AQP8 mRNA are expressed in rat
      small intestine. Immunoblot and immunohistochemistry experiments demonstrate that
      AQP7 and AQP8 proteins are present in the apical brush border membrane of
      intestinal epithelial cells. We investigated the effect of several metals and pH
      on the osmotic water permeability (Pf) of brush border membrane vesicles (BBMVs)
      and of AQP7 and AQP8 expressed in a cell line. Hg2+, Cu2+, and Zn2+ caused a
      significant decrease in the BBMV Pf, whereas Ni2+ and Li+ had no effect. AQP8
      transfected cells showed a reduction in Pf in the presence of Hg2+ and Cu2+,
      whereas AQP7-transfected cells were insensitive to all tested metals. The Pf of
      both BBMVs and cells transfected with AQP7 and AQP8 was not affected by pH
      changes within the physiological range, and the Pf of BBMVs alone was not
      affected by phlorizin or amiloride. Our results indicate that AQP7 and AQP8 may
      play a role in water movement via the apical domain of small intestine epithelial
      cells. AQP8 may contribute to the water-imbalance-related clinical symptoms
      apparent after ingestion of high doses of Hg2+ and Cu2+.

PMID- 18059527
TI  - Expression of fusion IL2-B7.1(IgV+C) and effects on T lymphocytes.
AB  - The search for an effective immunotherapeutic treatment for tumors is an
      important area of cancer research. To prepare a more effective form of the
      bifunctional fusion protein IL2-B7.1(IgV+C) and analyze its effect on the
      stimulation of T lymphocyte proliferation, we used DNAStar 5.03 software to
      predict the structural diversity and biochemical character of IL2-B7.1(IgV+C). We
      then prepared fusion protein IL2-B7.1(IgV+C) by establishing its prokaryotic
      expression system, and tested its effect on the stimulation of T lymphocytes in
      vitro. The results indicated that IL2-B7.1(IgV+C) correctly formed a secondary
      structure in which both IL2 and B7.1(IgV+C) maintained their original
      hydrophilicity and epitopes. Western blot analysis revealed that IL2-B7.1(IgV+C)
      was efficiently expressed. Our analysis of CTLL-2 and T-cell proliferation showed
      that recombinant human (rh) IL2-B7.1(IgV+C) exerted the combined stimulating
      effects of both rhIL2 and rh B7.1(IgV+C) on cell proliferation, and that these
      effects could be blocked by adding either anti-IL2 or anti-B7.1 monoclonal
      antibodies. A >2-fold increase in [3H]TdR incorporation compared with that of
      cells treated with recombinant protein IL2, or B7.1(IgV+C) alone, revealed that
      rhIL2-B7.1(IgV+C) had dose-dependent synergetic effects on T-cell activation in
      the presence of anti-CD3 monoclonal antibody. We concluded that the augmented
      potency of rhIL2-B7.1(IgV+C) resulted in a stronger stimulation of T-cell
      proliferation than either rhB7.1(IgV+C) or rhIL2 alone.

PMID- 18059528
TI  - Lipoprotein electrostatic properties regulate hepatic lipase association and
      activity.
AB  - The effect of lipoprotein electrostatic properties on the catalytic regulation of
      hepatic lipase (HL) was investigated. Enrichment of serum or very low density
      lipoprotein (VLDL) with oleic acid increased lipoprotein negative charge and
      stimulated lipid hydrolysis by HL. Similarly, enrichment of serum or isolated
      lipoproteins with the anionic phospholipids phosphatidylinositol (PI),
      phosphatidic acid, or phosphatidylserine also increased lipoprotein negative
      charge and stimulated hydrolysis by HL. Anionic lipids had a small effect on
      phospholipid hydrolysis, but significantly stimulated triacylglyceride (TG)
      hydrolysis. High density lipoprotein (HDL) charge appears to have a specific
      effect on lipolysis. Enrichment of HDL with PI significantly stimulated VLDL-TG
      hydrolysis by HL. To determine whether HDL charge affects the association of HL
      with HDL and VLDL, HL-lipoprotein interactions were probed immunochemically.
      Under normal circumstances, HL associates with HDL particles, and only small
      amounts bind to VLDL. PI enrichment of HDL blocked the binding of HL with HDL.
      These data indicate that increasing the negative charge of HDL stimulates VLDL-TG
      hydrolysis by reducing the association of HL with HDL. Therefore, HDL controls
      the hydrolysis of VLDL by affecting the interlipoprotein association of HL.
      Lipoprotein electrostatic properties regulate lipase association and are an
      important regulator of the binding and activity of lipolytic enzymes.

PMID- 18059529
TI  - Activated pericyte attenuates endothelial functions: nitric oxide-cGMP rescues
      activated pericyte-associated endothelial dysfunctions.
AB  - Hepatic stellate cells are liver-specific pericytes and exist in close proximity
      with endothelial cells. The activation of liver pericytes is intrinsic to liver
      pathogenesis, and leads to endothelial dysfunction, including the low
      bioavailability of nitric oxide (NO). However, the role of nitric oxide in
      pericyte-endothelium cross-talk has not yet been elucidated. This work examines
      the cellular mechanism of action of NO in pericyte-mediated endothelial
      dysfunction. We used in vitro coculture and conditioned medium systems to study
      the effects of activated liver pericytes on endothelial function, and an egg yolk
      vascular bed model was used to study the effects of activated pericytes on
      angiogenesis. This study also demonstrates that activated pericytes attenuate the
      migration, proliferation, permeability, and NO production of endothelial cells.
      Our results demonstrate that activated pericytes restrict angiogenesis in egg
      yolk vascular bed models, and NO supplementation recovers 70% of the inhibition.
      Our results also demonstrate that supplementation with NO, sildenafil citrate
      (phosphodiesterase inhibitor), and 8-bromo-cGMP (cGMP analog) partially recovers
      activated-pericyte-mediated endothelium dysfunction. We conclude that NO-cGMP
      alleviates activated-pericyte-associated endothelial dysfunction, including
      angiogenesis, in a cGMP-dependent manner.

PMID- 18059530
TI  - Excitation pressure regulates the activation energy for recombination events in
      the photosystem II reaction centres of Chlamydomonas reinhardtii.
AB  - Using in vivo thermoluminescence, we examined the effects of growth irradiance
      and growth temperature on charge recombination events in photosystem II reaction
      centres of the model green alga Chlamydomonas reinhardtii. We report that growth
      at increasing irradiance at either 29 or 15 degrees C resulted in comparable
      downward shifts in the temperature peak maxima (T(M)) for S2QB- charge pair
      recombination events, with minimal changes in S2QA- recombination events. This
      indicates that such growth conditions decrease the activation energy required for
      S2QB- charge pair recombination events with no concomitant change in the
      activation energy for S2QA- recombination events. This resulted in a decrease in
      the DeltaT(M) between S2QA- and S2QB- recombination events, which was reversible
      when shifting cells from low to high irradiance and back to low irradiance at 29
      degrees C. We interpret these results to indicate that the redox potential of QB
      was modulated independently of QA, which consequently narrowed the redox
      potential gap between QA and QB in photosystem II reaction centres. Since a
      decrease in the DeltaT(M) between S2QA- and S2QB- recombination events correlated
      with growth at increasing excitation pressure, we conclude that acclimation to
      growth under high excitation pressure narrows the redox potential gap between QA
      and QB in photosystem II reaction centres, enhancing the probability for reaction
      center quenching in C. reinhardtii. We discuss the molecular basis for the
      modulation of the redox state of QB, and suggest that the potential for reaction
      center quenching complements antenna quenching via the xanthophyll cycle in the
      photoprotection of C. reinhardtii from excess light.

PMID- 18059531
TI  - PAK: an essential motif for forming beta-turn structures and exhibiting the
      thrombolytic effect of P6A and its analogs.
AB  - Ala-Arg-Pro-Ala-Lys (ARPAK; also known as P6A) and 19 of its analogs were
      synthesized, and their thrombolytic activities were assessed in vitro and in
      vivo. The solution structures of 12 of the P6A analogs were determined using
      nuclear magnetic resonance (NMR) spectroscopy. The thrombolytic activity and
      conformational structure relationship was analyzed. We found that the Pro-Ala-Lys
      (PAK) sequence was essential for thrombolytic activity and was also responsible
      for the beta-turn structure found in the P6A analogs studied. The well defined
      beta turn may act as a binding head with the protruding lysine side-chain
      (positively charged) found at the target site for target recognition.
      Additionally, the N-terminal residue may be critical for thrombolytic activity,
      which for PAK-containing peptides, is likely achieved via a plasminogen-dependent
      pathway.

PMID- 18059532
TI  - A new apoptosis inhibitor, CIAPIN1 (cytokine-induced apoptosis inhibitor 1),
      mediates multidrug resistance in leukemia cells by regulating MDR-1, Bcl-2, and
      Bax.
AB  - We investigated the role of cytokine-induced apoptosis inhibitor 1 (CIAPIN1), a
      newly identified apoptosis inhibitor, in leukemia cell multidrug resistance (MDR)
      and its possible underlying mechanisms. CIAPIN1 was found to be overexpressed at
      the mRNA and protein levels in the vincristine-induced multidrug-resistant
      leukemia cell line HL-60/VCR, compared with HL-60, its parental cell line. In
      this study, we transfected HL-60 with a eukaryotic expression vector of CIAPIN1.
      In vitro drug sensitivity assays suggested that HL-60-CIAPIN1 cells conferred
      resistance to both P-glycoprotein (P-gp)-related and -unrelated drugs. Blocking
      CIAPIN1 expression in HL-60/VCR cells by CIAPIN1-specific small interfering RNA
      increased the cells' sensitivity to various chemotherapeutic drugs. Flow
      cytometry results suggested that CIAPIN1 expression could suppress adriamycin
      induced apoptosis, accompanied by a decreased accumulation and increased release
      of adriamycin. Semiquantitative RT-PCR, Western blot analysis, and luciferase
      reporter assays suggested that CIAPIN1 could significantly upregulate the
      expression of MDR-1 and Bcl-2, the transcription of the MDR-1 gene, as well as
      downregulate the expression of Bax. Additionally, the inhibition of CIAPIN1
      expression by RNA interference or P-gp inhibitor could partially reverse CIAPIN1
      mediated MDR. Taken together, our findings suggest that downregulating CIAPIN1
      could sensitize leukemia cells to chemotherapeutic drugs by downregulating MDR-1
      and Bcl-2 and by upregulating Bax, yet not altering either glutathione-S
      transferase activity or intracellular glutathione content in leukemia cells.
      Further study of CIAPIN1's function may reveal more of the mechanisms of leukemia
      MDR and result in the development of strategies to treat leukemia.

PMID- 18059533
TI  - Competitive inhibition of histone deacetylase activity by trichostatin A and
      butyrate.
AB  - Histone deacetylases (HDACs) play a pivotal role in gene expression through their
      involvement in chromatin remodeling. The abnormal targeting or retention of HDACs
      to DNA regulatory regions is observed in many cancers, and hence HDAC inhibitors
      are being tested as promising anti-tumor agents. The results of previous kinetic
      studies, characterizing trichostatin A (TSA), as well as butyrate, as HDAC
      noncompetitive inhibitors, conflict with crystallographic and homology modeling
      data suggesting that TSA should act as a competitive inhibitor. Our results
      demonstrate that each of the HDAC inhibitors TSA and butyrate inhibits HDAC
      activity in a competitive fashion. Co-immunoprecipitation studies show that the
      inhibition of HDAC1 and HDAC2 activity by TSA does not disturb the extensive
      level of their association in the human breast cancer cell line MCF-7. Moreover,
      the inhibition of HDAC activity by TSA does not interfere with the interaction of
      HDAC1 and HDAC2 with Sin3A, a core component of the Sin3 complex. Thus, repressor
      complexes such as Sin3, appear to be stable in the presence of TSA. The
      association of HDAC2 with transcription factor Sp1 is also not affected by TSA.

PMID- 18059535
TI  - Quantitative trait loci underlying the development of seed composition in soybean
      (Glycine max L. Merr.).
AB  - One hundred and forty-three F2:7 recombinant inbred lines (RILs) developed from
      the cross of soybean cultivars 'Charleston' and 'Dongnong 594' were analyzed for
      the quantitative trait loci (QTLs) underlying protein or oil content at 6
      different developmental stages by composite interval mapping with a mixed genetic
      model. The genotype x environment (GxE) interactions of the QTLs were also
      evaluated. Nineteen (2004) and 33 (2005) unconditional QTLs underlying seed
      protein or oil content at the different developmental stages were mapped onto 8
      and 9 linkage groups, respectively. The proportion of phenotypic variation
      explained by these QTLs ranged from 6.26% to 30.52% and from 5.38% to 28.47%,
      respectively. Fourteen (2004) and 21 (2005) conditional QTLs underlying seed
      protein or oil content were mapped onto 5 and 8 linkage groups, respectively. The
      proportion of phenotypic variation explained by these QTLs ranged from 2.97% to
      29.68% and from 5.42% to 31.96%, respectively. The numbers and types of QTLs and
      the genetic effect for the two traits were different at each developmental stage.
      However, several genomic regions that simultaneously control the development of
      both traits were detected. The genetic effect on protein content and oil content
      was opposite for loci in the marker interval Satt335-SSatt334, reflecting a
      negative correlation of protein content and oil content. A G x E interaction
      effect of some QTLs underlying protein or oil content at different growth periods
      was observed.

PMID- 18059536
TI  - Mapping EST-derived SSRs and ESTs involved in resistance to bacterial blight in
      Manihot esculenta.
AB  - Cassava (Manihot esculenta Crantz) is a major root crop widely grown in the
      tropics. Cassava bacterial blight, caused by Xanthomonas axonopodis pv. manihotis
      (Xam), is an important disease in Latin America and Africa resulting in
      significant losses. The preferred control method is the use of resistant
      genotypes. Mapping expressed sequence tags (ESTs) and determining their co
      localization with quantitative trait loci (QTLs) may give additional evidence of
      the role of the corresponding genes in resistance or defense. Twenty-one EST
      derived simple sequence repeats (SSRs) were mapped in 16 linkage groups. ESTs
      showing similarities with candidate resistance genes or defense genes were also
      mapped using strategies such as restriction fragment length polymorphisms,
      cleaved amplified polymorphic sequences, and allele-specific primers. In total,
      10 defense-related genes and 2 bacterial artificial chromosomes (BACs) containing
      resistance gene candidates (RGCs) were mapped in 11 linkage groups. Two new QTLs
      associated with resistance to Xam strains CIO121 and CIO151 were detected in
      linkage groups A and U, respectively. The QTL in linkage group U explained 61.6%
      of the phenotypic variance and was associated with an RGC-containing BAC. No
      correlation was found between the new EST-derived SSRs or other mapped ESTs and
      the new or previously reported QTLs.

PMID- 18059537
TI  - Microsatellite-based characterization of the Castanea sativa cultivar heritage of
      southern Switzerland.
AB  - Southern Switzerland has a long tradition of chestnut cultivation as a staple
      food. Local inhabitants constantly selected varieties according to the ripening
      period, the type of use, and the adaptability to the territory. As a result, the
      panorama of chestnut varieties is very complex, as reflected by more than 120
      different variety names in an area of 26,000 ha. Since 1994, 47 varieties have
      been conserved in the chestnut germplasm of southern Switzerland (CSS), including
      Marroni, Euro-Japanese, and French varieties. A selection of 164 individuals from
      the CSS was analysed by 8 SSR markers (4 of which were developed in this study).
      Microsatellite analysis indicated that the CSS was accurately established, as 86%
      of the individuals grafted were correctly labeled. The identification of 98
      genotypes, 10 clonal chestnut groups, 4 synonym groups, and 12 homonym groups
      reflected the complex ethnogeographical structure of the chestnut distribution.
      The 17 Marroni individuals considered clustered in 2 differentiated genetic
      groups instead of only 1 as expected. The fundamental problem of the frequent
      cases of homonymy and synonymy is discussed, as is the need for criteria for
      discriminating between polyclonal varieties and distinct homonymous varieties.

PMID- 18059538
TI  - SSR marker diversity of soybean aphid resistance sources in North America.
AB  - The soybean aphid (Aphis glycines Matsumura) has become a major pest of soybean
      in North America since 2000. Seven aphid resistance sources, PI 71506, Dowling,
      Jackson, PI 567541B, PI 567598B, PI 567543C, and PI 567597C, have been
      identified. Knowledge of genetic relationships among these sources and their
      ancestral parents will help breeders develop new cultivars with different
      resistance genes. The objective of this research was to examine the genetic
      relationships among these resistance sources. Sixty-one lines were tested with 86
      simple sequence repeat (SSR) markers from 20 linkage groups. Non-hierarchical
      (VARCLUS) and hierarchical (Ward's) clustering and multidimensional scaling (MDS)
      were used to determine relationships among the 61 lines. Two hundred and sixty
      two alleles of the 86 SSR loci were detected with a mean polymorphism information
      content of 0.36. The 61 lines were grouped into 4 clusters by both clustering
      methods and the MDS results consistently corresponded to the assigned clusters.
      The 7 resistance sources were clustered into 3 different groups corresponding to
      their geographical origins and known pedigree information, indicating genetic
      differences among these sources. The largest variation was found among
      individuals within different clusters by analysis of molecular variance.

PMID- 18059539
TI  - Characterization of Coffea chloroplast microsatellites and evidence for the
      recent divergence of C. arabica and C. eugenioides chloroplast genomes.
AB  - Comparative sequencing of >7 kb of highly variable chloroplast genome regions
      (atpB-rbcL, trnS-trnG, rpl22-rps19, and rps19-rpl2 spacers; introns in atpF,
      trnG, trnK, and rpl16) with microsatellites known from other angiosperms was
      carried out in Coffea. Samples comprised 8 diploid species of Coffea, 5
      individuals of tetraploid C. arabica representing geographically distant wild
      populations from Ethiopia, 2 commercial cultivars of C. arabica, and Psilanthus
      leroyi and Ixora coccinea as outgroups. Phylogeny reconstruction using maximum
      parsimony and Bayesian inference resulted in congruent topologies with high
      support for C. arabica and C. eugenioides being sisters. Partitioned analyses
      showed that all regions except the atpB-rbcL spacer resolved this sister-group,
      although this was often unsupported. The large sequence data set further shows
      that chloroplast genomes of C. arabica and C. eugenioides each possess
      apomorphies, indicating that not C. eugenioides but an ancestor or close relative
      of C. eugenioides is the maternal parent of C. arabica. Seven variable
      chloroplast microsatellites were characterized in Coffea. Most microsatellites
      are poly(A/T) stretches, whereas one in the trnS-trnG spacer has an (AT)n motif.
      Most strikingly, all individuals of C. arabica possess identical sequences,
      suggesting a single chloroplast haplotype. This can be explained by a recent
      origin of C. arabica in a unique allopolyploidization event, or by severe
      bottleneck effects in the evolutionary history of the species. Reconstruction of
      the evolution of microstructural mutations shows much higher levels of homoplasy
      in microsatellite loci than in other parts of spacers and introns.
      Microsatellites are inferred to evolve by insertion and deletion of 1 to 3 motif
      copies in one step.

PMID- 18059540
TI  - Molecular cloning, heterologous expression, and phylogenetic analysis of a novel
      y-type HMW glutenin subunit gene from the G genome of Triticum timopheevi.
AB  - A novel y-type high molecular weight (HMW) glutenin subunit gene from the G
      genome of Triticum timopheevi (2n=4x=28, AAGG) was isolated and characterized.
      Genomic DNA from accession CWI17006 was amplified and a 2200 bp fragment was
      obtained. Sequence analysis revealed a complete open reading frame including N-
      and C-terminal ends and a central repetitive domain encoding 565 amino acid
      residues. The molecular weight of the deduced subunit was 77,031, close to that
      of the x-type glutenin subunits. Its mature protein structure, however,
      demonstrated that it was a typical y-type HMW subunit. To our knowledge, this is
      the largest y-type subunit gene among Triticum genomes. The molecular structure
      and phylogenetic analysis assigned it to the G genome and it is the first
      characterized y-type HMW glutenin subunit gene from T. timopheevi. Comparative
      analysis and secondary structure prediction showed that the subunit possessed
      some unique characters, especially 2 large insertions of 45 (6 hexapeptides and a
      nonapeptide) and 12 (2 hexapeptides) amino acid residues that mainly contributed
      to its higher molecular weight and allowed more coils to be formed in its
      tertiary structure. Additionally, more alpha-helixes in the repeat domain of the
      subunit were found when compared with 3 other y-type subunits. We speculate that
      these structural characteristics improve the formation of gluten polymer. The
      novel subunit, expressed as a fusion protein in E. coli, moved more slowly in SDS
      PAGE than the subunit Bx7, so it was designated Gy7*. As indicated in previous
      studies, increased size and more numerous coils and alpha-helixes of the
      repetitive domain might enhance the functional properties of HMW glutenins.
      Consequently, the novel Gy7* gene could have greater potential for improving
      wheat quality.

PMID- 18059541
TI  - Identification and analysis of differentially expressed genes in differentiating
      xylem of Chinese fir (Cunninghamia lanceolata) by suppression subtractive
      hybridization.
AB  - Wood is an important raw material for global industries with rapidly increasing
      demand. To isolate the genes differentially expressed during xylogenesis of
      Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.), we used a novel system.
      Forward and reverse subtracted cDNA libraries were constructed using the
      suppression subtractive hybridization method; for the forward library we used
      cDNA from the mutant Dugansha as the tester and cDNA from the wild-type clone
      Jurong 0 as the driver, and for the reverse library we used Jurong 0 cDNA as the
      tester and Dugansha cDNA as the driver. Transcriptional profiling was performed
      using a macroarray with 4 digoxigenin-labeled probes. We obtained 618 and 409
      clones from the forward and the reverse subtracted library, respectively. A total
      of 405 unique expressed sequence tags (ESTs) were obtained. Forty percent of the
      ESTs exhibited homologies with proteins of known function and fell into 4 major
      classes: metabolism, cell wall biogenesis and remodeling, signal transduction,
      and stress. Real-time PCR was performed to confirm the results. The expression
      levels of 11 selected ESTs were consistent with both macroarray and real-time PCR
      results. The systematic analysis of genes involved in wood formation in Chinese
      fir provides valuable insights into the molecular mechanisms involved in xylem
      differentiation and is an important resource for forest research that can be
      directed toward understanding the genetic control of wood formation and future
      endeavors to modify wood and fiber properties for industrial use.

PMID- 18059543
TI  - Ectopic gene conversions in bacterial genomes.
AB  - We characterized the gene conversions found between the duplicated genes of 75
      bacterial genomes from five species groups (archaea, nonpathogenic and pathogenic
      firmicutes, and nonpathogenic and pathogenic proteobacteria). The number of gene
      conversions is positively correlated with the size of multigene families and the
      size of multigene families is not significantly different between pathogenic and
      nonpathogenic taxa. However, gene conversions occur twice as frequently in
      pathogenic species as in nonpathogenic species. Comparisons between closely
      related species also indicate a trend towards increased gene conversion in
      pathogenic species. Whereas the length of the conversions is positively
      correlated with flanking sequence similarity in all five groups, these
      correlations are smaller for pathogenic firmicutes and proteobacteria than for
      nonpathogenic firmicutes and proteobacteria. These results are consistent with
      our previous work on E. coli genomes and suggest that pathogenic bacteria allow
      recombination between more divergent gene sequences. This higher permissiveness
      is likely adaptive because it allows them to generate more genetic variability.

PMID- 18059542
TI  - Development of genomic microsatellite markers in Coffea canephora and their
      transferability to other coffee species.
AB  - Of the 103 accepted Coffea species, 70% are threatened with extinction but only a
      few of them have been studied. A set of 40 polymorphic microsatellite markers was
      developed using a GA/GT-enriched Coffea canephora genomic library. Amplification
      of these markers was tested in accessions of C. heterocalyx (a Critically
      Endangered species) and C. pseudozanguebariae (a Vulnerable species) belonging to
      different African geographical clades. All microsatellites were polymorphic in C.
      canephora, with a mean allele number per polymorphic locus of more than 3 (at
      least 9 genotypes were tested). Observed and expected heterozygosities calculated
      for C. canephora and C. pseudozanguebariae varied from 0.10 to 0.91 and from 0.20
      to 0.77, respectively. In total, 38 primer pairs (95%) were amplified in C.
      heterocalyx and C. pseudozanguebariae, indicating their high level of
      transferability across the genus Coffea. This large marker set will be useful for
      more extensive genetic studies of threatened Coffea species.

PMID- 18059544
TI  - Genome doubling and chromosome elimination with fragment recombination leading to
      the formation of Brassica rapa-type plants with genomic alterations in crosses
      with Orychophragmus violaceus.
AB  - In distant hybridization of plants, nonclassical hybrids with unexpected
      chromosome complements, chromosome elimination, and genetic introgression have
      been well documented. We obtained intergeneric hybrids between Brassica rapa, B.
      rapa var. chinensis, and another cruciferous species, Orychophragmus violaceus,
      following embryo rescue. Hybrids mainly displayed phenotypes of B. rapa, although
      certain O. violaceus or novel characteristics also appeared. Variable numbers of
      chromosomes were observed in somatic cells in the roots of plantlets on medium
      and in ovaries and pollen mother cells (PMCs). However, higher numbers were
      recorded in the roots. GISH revealed that the majority of ovary cells and PMCs
      contained 20 chromosomes of B. rapa with or without individual O. violaceus
      chromosomes or fragments added or introgressed. AFLP analysis showed that
      fragments deleted from the B. rapa genome were much more frequent than novel and
      O. violaceus fragments. The mechanisms involved genome doubling and successive
      elimination of O. violaceus chromosomes accompanied by fragment recombination and
      introgression, producing B. rapa-type plants with modified genetic constitutions
      and phenotypes.

PMID- 18059545
TI  - Introgression of wheat chromosome 2D or 5D into tritordeum leads to free
      threshing habit.
AB  - Hexaploid tritordeum is the amphiploid derived from the cross between the diploid
      wild barley Hordeum chilense and durum wheat. The non-free-threshing habit is a
      constraint to this species becoming a new crop. Three tritordeum lines (HT374,
      HT376, and HT382) showing the free-threshing habit were selected from crosses
      between tritordeum and bread wheat. All three lines were euploids, as revealed by
      mitotic chromosome counting. Genomic in situ hybridization analysis made it
      possible to distinguish differences among these lines. While the line HT382
      carries only 10 chromosomes from H. chilense, the lines HT374 and HT376 have 12.
      These results suggest that HT382 is a double chromosome substitution line between
      H. chilense and the wheat D genome, while HT374 and HT376 each have one pair of
      H. chilense (Hch) chromosomes substituted by wheat D chromosomes. Molecular
      characterization revealed that HT382 is a 1D/(1Hch), 2D/(2Hch) chromosome
      substitution line, whereas HT374 and HT376 have 5D/(5Hch) substitutions. On the
      basis of previous knowledge, it seems that the absence of chromosome 2Hch or 5Hch
      is more important for producing the free-threshing habit than the presence of
      chromosome 2D or 5D, while chromosome 1Hch seems to be unrelated to the trait.
      These free-threshing tritordeum lines constitute an important advance in the
      tritordeum breeding program.

PMID- 18059546
TI  - Structure, function, and evolution of plant O-methyltransferases.
AB  - Plant O-methyltransferases (OMTs) constitute a large family of enzymes that
      methylate the oxygen atom of a variety of secondary metabolites including
      phenylpropanoids, flavonoids, and alkaloids. O-Methylation plays a key role in
      lignin biosynthesis, stress tolerance, and disease resistance in plants. To gain
      insights into the evolution of the extraordinary diversity of plant O
      methyltransferases, and to develop a framework phylogenetic tree for improved
      prediction of the putative function of newly identified OMT-like gene sequences,
      we performed a comparative and phylogenetic analysis of 61 biochemically
      characterized plant OMT protein sequences. The resulting phylogenetic tree
      revealed two major groups. One of the groups included two sister clades, one
      comprising the caffeoyl CoA OMTs (CCoA OMTs) that methylate phenolic hydroxyl
      groups of hydroxycinnamoyl CoA esters, and the other containing the carboxylic
      acid OMTs that methylate aliphatic carboxyl groups. The other group comprised the
      remaining OMTs, which act on a diverse group of metabolites including
      hydroxycinnamic acids, flavonoids, and alkaloids. The results suggest that some
      OMTs may have undergone convergent evolution, while others show divergent
      evolution. The high number of unique conserved regions within the CCoA OMTs and
      carboxylic acid OMTs provide an opportunity to design oligonucleotide primers to
      selectively amplify and characterize similar OMT genes from many plant species.

PMID- 18059547
TI  - Estimating meiotic chromosome pairing and recombination parameters in telocentric
      trisomics.
AB  - Telocentric trisomics (telotrisomics; one arm of a metacentric chromosome present
      in addition to two complete genomes) are used in theoretical studies of pairing
      affinities and chiasma formation in competitive situations and applied in genome
      analysis, gene localization, gene transfer, and breakage of close linkages. These
      applications require knowledge of the recombination characteristics of
      telotrisomics. Appropriate cytological and molecular markers and favorable
      chromosome morphology are not always available or applicable for quantitative
      analyses. We developed new mathematical models for extracting the maximum
      information from simple metaphase I observations. Two types of telotrisomics of
      the short arm of chromosome 1R of rye (Secale cereale), including several
      genotypes, were used as test material. In simple telotrisomics, pairing between
      morphologically identical complete chromosomes was more frequent than pairing
      between the telocentric and either of the normal chromosomes. In the telocentric
      substitution, morphologically identical telocentrics paired less frequently with
      each other than either one with the normal chromosome. Pairing partner switch was
      significant. Interaction between the two arms was variable. Variation within
      plants was considerable. Telotrisomics without markers are suitable for analyzing
      pairing preferences, for gene localization and gene transfer, and for breaking
      tight linkages, but less so for genome analysis.

PMID- 18059548
TI  - Genome size and genome evolution in diploid Triticeae species.
AB  - One of the intriguing issues concerning the dynamics of plant genomes is the
      occurrence of intraspecific variation in nuclear DNA amount. The aim of this work
      was to assess the ranges of intraspecific, interspecific, and intergeneric
      variation in nuclear DNA content of diploid species of the tribe Triticeae
      (Poaceae) and to examine the relation between life form or habitat and genome
      size. Altogether, 438 plants representing 272 lines that belong to 22 species
      were analyzed. Nuclear DNA content was estimated by flow cytometry. Very small
      intraspecific variation in DNA amount was found between lines of Triticeae
      diploid species collected from different habitats or between different morphs. In
      contrast to the constancy in nuclear DNA amount at the intraspecific level, there
      are significant differences in genome size between the various diploid species.
      Within the genus Aegilops, the 1C DNA amount ranged from 4.84 pg in A. caudata to
      7.52 pg in A. sharonensis; among genera, the 1C DNA amount ranged from 4.18 pg in
      Heteranthelium piliferum to 9.45 pg in Secale montanum. No evidence was found for
      a smaller genome size in annual, self-pollinating species relative to perennial,
      cross-pollinating ones. Diploids that grow in the southern part of the group's
      distribution have larger genomes than those growing in other parts of the
      distribution. The contrast between the low variation at the intraspecific level
      and the high variation at the interspecific one suggests that changes in genome
      size originated in close temporal proximity to the speciation event, i.e.,
      before, during, or immediately after it. The possible effects of sudden changes
      in genome size on speciation processes are discussed.

PMID- 18059549
TI  - Expression analysis of defense-related genes in wheat in response to infection by
      Fusarium graminearum.
AB  - Fusarium head blight (FHB), caused by the fungi Fusarium graminearum and Fusarium
      culmorum, is a worldwide disease of wheat (Triticum aestivum L.). The Chinese
      cultivar Ning 7840 is one of a few wheat cultivars with resistance to FHB.
      GeneCalling, an open-architecture mRNA-profiling technology, was used to identify
      differentially expressed genes induced or suppressed in spikes of Ning 7840 after
      infection by F. graminearum. One hundred and twenty-five cDNA fragments
      representing transcripts differentially expressed in wheat spikes were
      identified. Based on BLASTN and BLASTX analyses, putative functions were assigned
      to some of the genes: 28 were assigned functions in primary metabolism and
      photosynthesis, 7 were involved in defense response, 14 were involved in gene
      expression and regulation, 24 encoded proteins associated with structure and
      protein synthesis, 42 lacked homology to sequences in the database, and 3 were
      similar to cloned multidrug resistance or disease resistance proteins. Of
      particular interest in this study were genes associated with resistance and
      defense against pathogen infection. Real-time quantitative reverse-transcription
      PCR indicated that of 51 genes tested, 19 showed 2-fold or greater induction or
      suppression in infected Ning 7840 in comparison with the water-treated control.
      The remaining 32 genes were not significantly induced or suppressed in infected
      Ning 7840 compared with the control. Subsequently, these 19 induced or suppressed
      genes were examined in the wheat line KS24-1, containing FHB resistance derived
      from Lophopyrum elongatum, and Len, an FHB-susceptible wheat cultivar. The
      temporal expression of some of these sequences encoding resistance proteins or
      defense-related proteins showed FHB (resistance specific) induction, suggesting
      that these genes play a role in protection against toxic compounds in plant
      fungus interactions. On the basis of comprehensive expression profiling of
      various biotic or abiotic stress response genes revealed by quantitative PCR in
      this study and other supporting data, we hypothesized that the plant-pathogen
      interactions may be highly integrated into a network of diverse biosynthetic
      pathways.

PMID- 18059550
TI  - The orphan nuclear receptor DHR38 influences transcription of the DOPA
      decarboxylase gene in epidermal and neural tissues of Drosophila melanogaster.
AB  - The DOPA decarboxylase gene (Ddc) belongs to the "early-late" class of ecdysone
      inducible genes in Drosophila melanogaster. Its expression is up-regulated in
      epidermal tissues by the ecdysone receptor acting through a response element,
      EcRE. In this paper, we show that another member of the nuclear receptor
      superfamily, DHR38, may act as a repressor of epidermal Ddc while inducing Ddc
      expression in neuronal cells. DHR38 does not behave as a classical co-repressor
      of the ecdysone receptor though, since the site through which DHR38 acts is
      distinct from the EcRE. Ectopic expression of a Dhr38 cDNA from a heat-shock
      promoter completely repressed transcription from the endogenous Ddc promoter and
      from an intact reporter construct in the hypoderm and in imaginal discs. Ectopic
      DHR38 had no effect on the transcription of a reporter driven by a Ddc fragment
      missing the DHR38 binding site. Neither reporter expression nor endogenous Ddc
      transcript levels were affected in a Dhr38 mutant background. Because most mutant
      organisms pupariate apparently normally and many of these survive to eclose, we
      believe that some functional redundancy exists within the Dhr38 regulatory
      network operating in epidermal tissues. In contrast to its apparent repressor
      function in epidermal tissues, DHR38 may act as a positive regulator of neural
      Ddc expression. Ectopic expression of DHR38 throughout the CNS induced as much as
      a 20-fold increase in Ddc transcripts in the set of neurons in which DDC normally
      appears.

PMID- 18059551
TI  - Conserved synteny of genes between chromosome 15 of Bombyx mori and a chromosome
      of Manduca sexta shown by five-color BAC-FISH.
AB  - The successful assignment of the existing genetic linkage groups (LGs) to
      individual chromosomes and the second-generation linkage map obtained by mapping
      a large number of bacterial artificial chromosome (BAC) contigs in the silkworm,
      Bombyx mori, together with public nucleotide sequence databases, offer a powerful
      tool for the study of synteny between karyotypes of B. mori and other
      lepidopteran species. Conserved synteny of genes between particular chromosomes
      can be identified by comparatively mapping orthologous genes of the corresponding
      linkage groups with the help of BAC-FISH (fluorescent in situ hybridization).
      This technique was established in B. mori for 2 differently labeled BAC probes
      simultaneously hybridized to pachytene bivalents. To achieve higher-throughput
      comparative mapping using BAC-FISH in Lepidoptera, we developed a protocol for
      five-color BAC-FISH, which allowed us to map simultaneously 6 different BAC
      probes to chromosome 15 in B. mori. We identified orthologs of 6 B. mori LG15
      genes (RpP0, RpS8, eIF3, RpL7A, RpS23, and Hsc70) for the tobacco hornworm,
      Manduca sexta, and selected the ortholog-containing BAC clones from an M. sexta
      BAC library. All 6 M. sexta BAC clones hybridized to a single M. sexta bivalent
      in pachytene spermatocytes. Thus, we have confirmed the conserved synteny between
      the B. mori chromosome 15 and the corresponding M. sexta chromosome (hence
      provisionally termed chromosome 15).

PMID- 18059552
TI  - Analysis of behavior using genetical genomics in mice as a model: from alcohol
      preferences to gene expression differences.
AB  - Most familial behavioral phenotypes result from the complex interaction of
      multiple genes. Studies of such phenotypes involving human subjects are often
      inconclusive owing to complexity of causation and experimental limitations.
      Studies of animal models argue for the use of established genetic strains as a
      powerful tool for genetic dissection of behavioral disorders and have led to the
      identification of rare genes and genetic mechanisms implicated in such
      phenotypes. We have used microarrays to study global gene expression in adult
      brains of four genetic strains of mice (C57BL/6J, DBA/2J, A/J, and BALB/c). Our
      results demonstrate that different strains show expression differences for a
      number of genes in the brain, and that closely related strains have similar
      patterns of gene expression as compared with distantly related strains. In
      addition, among the 24 000 genes and ESTs on the microarray, 77 showed at least a
      1.5-fold increase in the brains of C57BL/6J mice as compared with those of DBA/2J
      mice. These genes fall into such functional categories as gene regulation,
      metabolism, cell signaling, neurotransmitter transport, and DNA/RNA binding. The
      importance of these findings as a novel genetic resource and their use and
      application in the genetic analysis of complex behavioral phenotypes,
      susceptibilities, and responses to drugs and chemicals are discussed.

PMID- 18059553
TI  - Mapping barley genes to chromosome arms by transcript profiling of wheat-barley
      ditelosomic chromosome addition lines.
AB  - Wheat-barley disomic and ditelosomic chromosome addition lines have been used as
      genetic tools for a range of applications since their development in the 1980s.
      In the present study, we used the Affymetrix Barley1 GeneChip for comparative
      transcript analysis of the barley cultivar Betzes, the wheat cultivar Chinese
      Spring, and Chinese Spring - Betzes ditelosomic chromosome addition lines to
      physically map barley genes to their respective chromosome arm locations. We
      mapped 1257 barley genes to chromosome arms 1HS, 2HS, 2HL, 3HS, 3HL, 4HS, 4HL,
      5HS, 5HL, 7HS, and 7HL based on their transcript levels in the ditelosomic
      addition lines. The number of genes assigned to individual chromosome arms ranged
      from 24 to 197. We validated the physical locations of the genes through
      comparison with our previous chromosome-based physical mapping, comparative in
      silico mapping with rice and wheat, and single feature polymorphism (SFP)
      analysis. We found our physical mapping of barley genes to chromosome arms to be
      consistent with our previous physical mapping to whole chromosomes. In silico
      comparative mapping of barley genes assigned to chromosome arms revealed that the
      average genomic synteny to wheat and rice chromosome arms was 63.2% and 65.5%,
      respectively. In the 1257 mapped genes, we identified SFPs in 924 genes between
      the appropriate ditelosomic line and Chinese Spring that supported physical map
      placements. We also identified a single small rearrangement event between rice
      chromosome 9 and barley chromosome 4H that accounts for the loss of synteny for
      several genes.

PMID- 18059554
TI  - Chromosomal rearrangements in wheat: their types and distribution.
AB  - Four hundred and sixty polyploid wheat accessions and 39 triticale forms from 37
      countries of Europe, Asia, and USA were scored by C-banding for the presence of
      translocations. Chromosomal rearrangements were detected in 70 of 208 accessions
      of tetraploid wheat, 69 of 252 accessions of hexaploid wheat, and 3 of 39
      triticale forms. Altogether, 58 types of major chromosomal rearrangements were
      identified in the studied material; they are discussed relative to 11 additional
      translocation types described by other authors. Six chromosome modifications of
      unknown origin were also observed. Among all chromosomal aberrations identified
      in wheat, single translocations were the most frequent type (39), followed by
      multiple rearrangements (9 types), pericentric inversions (9 types), and
      paracentric inversions (3 types). According to C-banding analyses, the
      breakpoints were located at or near the centromere in 60 rearranged chromosomes,
      while in 52 cases they were in interstitial chromosome regions. In the latter
      case, translocation breakpoints were often located at the border of C-bands and
      the euchromatin region or between two adjacent C-bands; some of these regions
      seem to be translocation "hotspots". Our results and data published by other
      authors indicate that the B-genome chromosomes are involved in translocations
      most frequently, followed by the A- and D-genome chromosomes; individual
      chromosomes also differ in the frequencies of translocations. Most translocations
      were detected in 1 or 2 accessions, and only 11 variants showed relatively high
      frequencies or were detected in wheat varieties of different origins or from
      different species. High frequencies of some translocations with a very restricted
      distribution could be due to a "bottleneck effect". Other types seem to occur
      independently and their broad distribution can result from selective advantages
      of rearranged genotypes in diverse environmental conditions. We found significant
      geographic variation in the spectra and frequencies of translocation in wheat:
      the highest proportions of rearranged genotypes were found in Central Asia, the
      Middle East, Northern Africa, and France. A low proportion of aberrant genotypes
      was characteristic of tetraploid wheat from Transcaucasia and hexaploid wheat
      from Middle Asia and Eastern Europe.

PMID- 18059555
TI  - Investigations of 5S rDNA of Vitis vinifera L.: sequence analysis and physical
      mapping.
AB  - Here we report the first results of a study of 5S rDNA of Vitis vinifera. 5S rDNA
      sequences from seven genotypes were amplified by PCR, cloned, and sequenced.
      Three types of repeats were found. Two variants, denominated long repeat and
      short repeat, appeared to be the main components of the 5S rDNA of this species,
      since they were found in all genotypes analyzed. They differed markedly from each
      other in both the length and the nucleotide composition of the spacers. The third
      variant, classified as DEL short repeat, differs from the short repeat owing to a
      large deletion in the spacer region. It appears to be the most recent repeat
      type, since it was identified in only one genotype. The organization of the 5S
      rDNA repeat unit variants was investigated by amplifying the genomic DNA with
      primers designed on the sequence of the long and short spacers. The PCR-amplified
      fragments showed that the long repeat is associated with the other two repeats,
      indicating that in V. vinifera different repeat units coexist within the same
      tandem array. FISH analysis demonstrated that 5S rRNA genes are localized at a
      single locus. The variability of 5S rDNA repeats is discussed in relation to the
      putative allopolyploid origin of V. vinifera.

PMID- 18059556
TI  - Corticotropin releasing hormone is a promising candidate gene for marbling and
      subcutaneous fat depth in beef cattle.
AB  - The gene corticotropin releasing hormone (CRH) is mapped on bovine chromosome 14
      (BTA14), where more than 30 fat-related quantitative trait loci (QTLs) have been
      reported in dairy and beef cattle. The gene product regulates secretion of
      adrenocorticotrophin hormone, the hypothalamic-pituitary-adrenal axis, and
      multiple hypothalamic functions; therefore, we hypothesized that CRH is a
      promising candidate gene for beef marbling score (BMS) and subcutaneous fat depth
      (SFD) in a Wagyu x Limousin F2 population. Two pairs of primers were designed and
      a total of 5 single nucleotide polymorphisms (SNPs) were identified: g.9657C>T,
      c.10718G>C, c.10841G>A, c.10893A>C, and c.10936G>C (AAFC03076794.1). Among the 4
      cSNPs, c.10718G>C, c.10841G>A, and c.10936G>C are missense mutations leading to
      amino acid changes from arginine to proline, from serine to asparagine, and from
      aspartic acid to histidine, respectively. These 5 SNPs were genotyped on ~250 F2
      progeny, but only 4 were selected as tagging SNPs for association analysis
      because no historical recombination was observed between c.10718G>C and
      c.10893A>C. Statistical analysis showed that g.9657C>T, c.10718G>C, and
      c.10936G>C and their haplotypes had significant effects on SFD, but only
      c.10936G>C was significantly associated with BMS. The SNP in the promoter
      (g.9657C>T) led to gain/loss of a CpG site and 4 potential regulatory binding
      sites. Different haplotypes among the 4 cSNPs significantly affected mRNA
      secondary structures but were not associated with phenotypes. Overall, our
      results provide further evidence that CRH is a promising candidate gene for a
      concordant QTL related to lipid metabolism in mammals.

PMID- 18059557
TI  - Evidence of the modulation of mRNA splicing fidelity in humans by oxidative
      stress and p53.
AB  - The majority of human genes generate mRNA splice variants and while there is
      little doubt that alternative splicing is an important biological phenomenon, it
      has also become apparent that some splice variants are associated with disease.
      To elucidate the molecular mechanisms responsible for generating aberrant splice
      variants, we have investigated alternative splicing of the human genes HPRT and
      POLB following oxidative stress in different genetic backgrounds. Our study
      revealed that splicing fidelity is sensitive to oxidative stress. Following
      treatment of cells with H2O2, the overall frequency of aberrant, unproductive
      splice variants increased in both loci. At least in POLB, splicing fidelity is
      p53 dependent. In the absence of p53, the frequency of POLB splice variants is
      elevated but oxidative stress does not further increase the frequency of splice
      variants. Our data indicate that mis-splicing following oxidative stress
      represents a novel and significant genotoxic outcome and that it is not simply
      DNA lesions induced by oxidative stress that lead to mis-splicing but changes in
      the alternative splicing machinery itself.

PMID- 18059558
TI  - Bacterial artificial chromosome-based physical map of Gibberella zeae (Fusarium
      graminearum).
AB  - Fusarium graminearum is the primary causal pathogen of Fusarium head blight of
      wheat and barley. To accelerate genomic analysis of F. graminearum, we developed
      a bacterial artificial chromosome (BAC)-based physical map and integrated it with
      the genome sequence and genetic map. One BAC library, developed in the HindIII
      restriction enzyme site, consists of 4608 clones with an insert size of
      approximately 107 kb and covers about 13.5 genome equivalents. The other library,
      developed in the BamHI restriction enzyme site, consists of 3072 clones with an
      insert size of approximately 95 kb and covers about 8.0 genome equivalents. We
      fingerprinted 2688 clones from the HindIII library and 1536 clones from the BamHI
      library and developed a physical map of F. graminearum consisting of 26 contigs
      covering 39.2 Mb. Comparison of our map with the F. graminearum genome sequence
      showed that the size of our physical map is equivalent to the 36.1 Mb of the
      genome sequence. We used 31 sequence-based genetic markers, randomly spaced
      throughout the genome, to integrate the physical map with the genetic map. We
      also end-sequenced 17 BamHI BAC clones and identified 4 clones that spanned gaps
      in the genome sequence. Our new integrated map is highly reliable and useful for
      a variety of genomics studies.

PMID- 18059559
TI  - Association mapping of leaf traits, flowering time, and phytate content in
      Brassica rapa.
AB  - Association mapping was used to investigate the genetic basis of variation within
      Brassica rapa, which is an important vegetable and oil crop. We analyzed the
      variation of phytate and phosphate levels in seeds and leaves and additional
      developmental and morphological traits in a set of diverse B. rapa accessions and
      tested association of these traits with AFLP markers. The analysis of population
      structure revealed four subgroups in the population. Trait values differed
      between these subgroups, thus defining associations between population structure
      and trait values, even for traits such as phytate and phosphate levels. Marker
      trait associations were investigated both with and without taking population
      structure into account. One hundred and seventy markers were found to be
      associated with the observed traits without correction for population structure.
      Association analysis with correction for population structure led to the
      identification of 27 markers, 6 of which had known map positions; 3 of these were
      confirmed in additional QTL mapping studies.

PMID- 18059560
TI  - Detection of Bacillus cereus virulence factors in commercial products of Bacillus
      thuringiensis and expression of diarrheal enterotoxins in a target insect.
AB  - We examined isolates from 4 commercial bioinsecticides based on different strains
      of Bacillus thuringiensis subspecies (kurstaki, israelensis, aizawai, and
      tenebrionis) for the presence of genes encoding proteins with known
      enterotoxigenicity (nhe, hbl, cytk, ces) and various other putative virulence
      genes (piplc, sph, bceT, entFM, entS, entT). The piplc and bceT sequences were
      present in all the isolates; sph was found in aizawai and israelensis; entFM only
      in israelensis; and entS in kurstaki, israelensis, and tenebrionis. Our results
      corroborate previous findings that isolates used in commercial products contain
      all nhe and hbl component genes but not the ces gene. We ascertained that the
      cytK gene present in the kurstaki-, israelensis-, and aizawai-based products
      belongs to the cytK-2 type and not the more toxigenic cytK-1 variant originally
      isolated from enterotoxic Bacillus cereus. We provide the first evidence that
      hemolytic (hblA) and nonhemolytic (nheA, nheB, nheC) enterotoxin genes are
      expressed during septicemia in a target insect. This opens the door for their
      possible participation in pathogenesis in target insects. If enterotoxins do not
      contribute to bacterial pathogenesis in target insects, their genes could be
      deleted from commercial production strains to pre-empt perceptions of public
      health risks.

PMID- 18059561
TI  - ACC deaminase from plant growth-promoting bacteria affects crown gall
      development.
AB  - In addition to the well-known roles of indoleacetic acid and cytokinin in crown
      gall formation, the plant hormone ethylene also plays an important role in this
      process. Many plant growth-promoting bacteria (PGPB) encode the enzyme 1
      aminocyclopropane-1-carboxylate (ACC) deaminase, which can degrade ACC, the
      immediate precursor of ethylene in plants, to alpha-ketobutyrate and ammonia and
      thereby lower plant ethylene levels. To study the effect of ACC deaminase on
      crown gall development, an ACC deaminase gene from the PGPB Pseudomonas putida
      UW4 was introduced into Agrobacterium tumefaciens C58, so that the effect of ACC
      deaminase activity on tumour formation in tomato and castor bean plants could be
      assessed. Plants were also coinoculated with A. tumefaciens C58 and P. putida UW4
      or P. putida UW4-acdS- (an ACC deaminase minus mutant strain). In both types of
      experiments, it was observed that the presence of ACC deaminase generally
      inhibited tumour development on both tomato and castor bean plants.

PMID- 18059562
TI  - Antifungal susceptibility of bloodstream yeasts isolated at a public children's
      hospital in Brazil: comparison of the Etest and the AFST-EUCAST microdilution
      method.
AB  - This study compared the minimum inhibitory concentration (MIC) results from the
      proposed standard methods of the Antifungal Susceptibility Testing Subcommittee
      of the European Committee on Antibiotic Susceptibility Testing (AFST-EUCAST) with
      the commercial system Etest(R) in the evaluation of susceptibility to
      flucytosine, fluconazole, itraconazole, voriconazole, and amphotericin B of 136
      Candida spp. isolated from the blood of hospitalized children. The results
      presented a greater agreement among Etest(R) MICs +/-2 log2 dilutions of AFST
      EUCAST for fluconazole (98.1% and 96.3%) and voriconazole (100% and 100%) for
      Candida albicans and Candida parapsilosis. For Candida glabrata, the agreement
      was greater only for fluconazole (81.8%) and voriconazole (100%). For
      amphotericin B, the agreement between the methods was low for all species. The
      agreement percentage among the Etest(R) and AFST-EUCAST susceptibility profiles
      was high according to the MIC breakpoints recommended by the M27-A2 protocol for
      the majority of the yeasts, except for fluconazole and itraconazole against
      Candida tropicalis and for itraconazole against C. glabrata and Candida krusei.
      According to both methodologies, a great number of Candida spp. isolates showed
      an in vitro susceptibility to all evaluated antifungal agents. Overall, both
      procedures can be reliable techniques for susceptibility tests of yeasts, but the
      assessment of interlaboratory agreement and correlation of MICs by different
      methods with in vivo response are of great importance.

PMID- 18059563
TI  - Diversity of tet resistance genes in tetracycline-resistant bacteria isolated
      from a swine lagoon with low antibiotic impact.
AB  - Tetracycline resistance has been extensively studied and shown to be widespread.
      A number of previous studies have clearly demonstrated that a variety of
      tetracycline resistance genes are present in swine fecal material, treatment
      lagoons, and the environments surrounding concentrated animal feeding operations
      (CAFOs). The diversity of tetracycline resistance within a swine lagoon located
      at a CAFO that used only bacitricin methylene disalicylate as an antibiotic was
      evaluated by screening 85 tetracycline-resistant isolates for the presence of 18
      different genes by performing PCR with primers that target tetracycline efflux
      genes of Gram-negative bacteria and ribosomal protection proteins. In addition,
      partial 16S rRNA sequences from each of these isolates were sequenced to
      determine the identity of these isolates. Of the 85 isolates examined, 17 may
      represent potential novel species based on BLAST results. Greater than 50% of the
      isolates (48 out of 85) were found to not contain targeted tet efflux genes.
      Though minimum inhibitory concentrations ranged widely (16 - >256 mg/L), these
      values did not give an indication of the tet genes present. Ten new genera were
      identified that contain at least one tet efflux gene. Five other genera possessed
      tet efflux genes that were not found in these organisms previously.
      Interestingly, none of the isolates possessed any of the selected ribosomal
      protection protein genes. Though tetracycline resistance was found in bacteria
      isolated from a swine CAFO lagoon, it appears that the limited antibiotic use at
      this CAFO might have impacted the presence and diversity of tetracycline
      resistance genes.

PMID- 18059564
TI  - Induction of oxalate decarboxylase by oxalate in a newly isolated Pandoraea sp.
      OXJ-11 and its ability to protect against Sclerotinia sclerotiorum infection.
AB  - Pandoraea sp. OXJ-11 has been shown to produce an oxalate decarboxylase. The
      enzyme could be induced by increasing the oxalate in the medium. An increasing
      concentration of yeast extract was able to stimulate the cell growth but could
      not increase the specific oxalate decarboxylase activity. The oxalate
      decarboxylase was produced maximally at 25-35 degrees C and pH 4.0-9.0, favoring
      its potential application in protection of host plants from oxalate-producing
      phytopathogens. The influence of glucose on the induction of oxalate
      decarboxylase by oxalate was examined, and it was found that glucose inhibited
      the production of the oxalate decarboxylase. Resistance results showed that
      Pandoraea sp. OXJ-11 was capable of suppressing Sclerotinia sclerotiorum
      infection on detached leaflets of Brassica napus plants.

PMID- 18059565
TI  - Identification of iron-regulated cellular proteins, Fe3+-reducing and -chelating
      compounds, in the white-rot fungus Perenniporia medulla-panis.
AB  - In this paper, we present the responses of the white-rot fungus Perenniporia
      medulla-panis to iron availability with regard to alterations in growth,
      expression of cellular proteins, Fe3+-reducing activity, and Fe3+ chelators
      production. Iron supplementation stimulated fungal growth but did not result in a
      significant increase in biomass production. Catechol and hydroxamate derivatives
      were produced mainly under iron deficiency, and their productions were repressed
      under iron supplementation conditions. Perenniporia medulla-panis showed several
      cellular proteins in the range of 10-90 kDa. Some of them showed negative iron
      regulation. Iron-supplemented medium also repressed both cell surface and
      extracellular Fe3+-reducing activities; however, the highest cell surface
      activity was detected at the initial growth phase, whereas extracellular activity
      increased throughout the incubation period. No significant production of
      chelators and extracellular Fe3+-reducing activity were observed within the
      initial growth phase, suggesting that the reduction of Fe3+ to Fe2+ is performed
      by ferrireductases.

PMID- 18059566
TI  - The antioxidants dimethylsulfoxide and dimethylthiourea affect the immediate
      adhesion responses of larval haemocytes from 3 lepidopteran insect species.
AB  - Antioxidants, dimethylsulfoxide (DMSO) and dimethylthiourea (DMTU), at
      concentrations not affecting the viability of blood cells (haemocytes) from the
      larval stage of 3 lepidopteran insects - Galleria mellonella, Lymantria dispar,
      and Malacosoma disstria - differed in their influence on the innate binding of
      haemocytes to glass, bacteria to haemocytes, and on humoral responses to alien
      materials. In vitro DMSO had little effect, whereas DMTU substantially impaired
      the adhesion of the haemocyte types, the plasmatocytes and granular cells, to
      slides as well as the attachment of Bacillus subtilis to these haemocytes.
      Although both antioxidants increased lysozyme and phenoloxidase activities, there
      was no correlation of enzyme activity and haemocyte adhesion responses, possibly
      reflecting sequestered radicals. Nitric oxide and hydroxyl radicals offset the
      DMTU effect. In the absence of antioxidants, inactivate protein kinases A (PKA)
      and C (PKC) enhanced haemocyte aggregation. In general, DMSO, as opposed to DMTU,
      did not alter the effects of PKA and PKC activators and inhibitors on haemocyte
      aggregation or of PKC and PKA activities. High concentrations of DMSO and all
      levels of DMTU, although inhibiting PKA and PKC, inhibited haemocyte adhesion to
      slides. Comparable results occurred for DMTU-treated haemocytes incubated with B.
      subtilis. In vivo DMSO, unlike DMTU, did not impair plasmatocyte or granular cell
      responses to foreign materials, including bacterial removal from the haemolymph
      and nodulation.

PMID- 18059567
TI  - Genetic and phenotypic diversity of Bifidobacterium thermacidophilum fecal
      isolates from newborns.
AB  - This study was undertaken to genetically identify and phenotypically characterize
      14 bifidobacteria isolated from 20 breast-fed newborns. These isolates showed 98%
      99% similarity to Bifidobacterium thermacidophilum subsp. suis based on 16S rDNA.
      Further analysis by pulsed-field gel electrophoresis of chromosomal DNA digested
      with XbaI revealed 4 distinct restriction patterns. The predominant pattern,
      shared by 8 (57%) isolates, produced a macro-restriction profile with about 13
      large fragments ranging in size from >242.5 to 23.1 kb, whereas the other 6
      displayed 3 distinct restriction profiles all characterized by more micro- than
      macro-restriction, with fragments ranging in size from 97 to 9.4 kb. Phenotypic
      characteristics, including carbohydrate fermentation profile, maximal growth
      temperature, and antibiotic susceptibility, varied widely even among strains
      showing the same restriction profile. The presence of B. thermacidophilum in
      stools of newborn infants may indicate the potential of these bacteria for aiding
      the development of the intestinal ecosystem.

PMID- 18059568
TI  - Serological profiling with Chlamycheck, a commercial multiplex recombinant
      antigen Western blot assay of chlamydial infections.
AB  - A new chlamydial test system, the Chlamycheck assay, which uses 4 purified
      recombinant antigens of Chlamydia trachomatis and Chlamydophila pneumoniae and
      one antigen of Chlamydophila psittaci, has been developed and commercialized. We
      investigated the reactivities of the recombinant antigens with sera from a group
      of 30 patients with acute Chlamydia trachomatis infection, 88 patients consulting
      for sexually transmitted infections, and 46 patients with serological evidence of
      Chlamydophila pneumoniae infection. The results obtained from human and infected
      mouse sera suggest that Chlamycheck serology against multiple proteins may
      provide additional useful information that is not available by conventional whole
      elementary body microimmunofluorescence or single-antigen enzyme-linked
      immunosorbent assay serology. Specific serological profiles were associated with
      acute versus past Chlamydia trachomatis infection or with Chlamydia trachomatis
      primo-infection versus infection in a Chlamydophila pneumoniae history context.

PMID- 18059569
TI  - Soil properties that impact yeast and actinomycete numbers in sandy low nutrient
      soils.
AB  - To explore the beneficial qualities or detrimental consequences of cultureable
      soil yeasts, it is important to understand which physicochemical soil properties
      most impact populations of these unicellular fungi in their natural habitat. The
      goal of this study was to determine which soil properties dictate yeast numbers
      in pristine sandy, low nutrient soils within a semi-arid region. A correlation
      matrix of the data obtained for 19 different environmental variables indicated a
      negative correlation between soil pH and yeast numbers. Using general regression
      models, it was demonstrated that soil pH and copper concentration were the 2
      variables that correlated best with soil yeast counts in these soils. However,
      soil moisture content was found to be the environmental factor with the most
      impact on cultureable actinomycetes and heterotrophic microbes. The study also
      demonstrated that divalent cation availability might impact the size of both
      yeast and prokaryote populations in these soils.

PMID- 18059570
TI  - Immune complexes in early Lyme disease.
AB  - The study investigated the presence of Borrelia-specific antibodies captured in
      immune complexes (ICs) in patients with early Lyme disease manifested by erythema
      migrans. Out of 18 patients, 15 (83.3%) tested positive for polyethylene glycol
      precipitated ICs containing IgM antibodies, while only 4 (22.2%) were IgG
      positive. These results are in accordance with our findings obtained by standard
      ELISA and recombinant blot, which indicated that ICs might be used for
      serological diagnosis of the early disease.

PMID- 18059571
TI  - Promoting food intake in older adults living in the community: a review.
AB  - Older adults (>65 y) living in the community have the potential to have
      significant nutrition concerns and deficits owing to the physiological, social,
      and psychological changes that occur with ageing. However, poor nutrition should
      not be considered an inevitable consequence of ageing. Older adults are quite
      heterogenous, including those ageing "successfully", "usually", and at
      "accelerated" rates. By improving the nutritional status of older adults,
      significant health and quality of life gains can be realized. These three
      subgroups of older adults have different concerns and risk factors and thus need
      different interventions. A substantial amount of research on older adult
      nutrition needs, determinants of food intake, risk of poor nutrition, and
      interventions has occurred in the past decade in Canada. The purpose of this
      review is to summarize this research and identify how nutrition promotion for
      older adults can be improved. Research to date indicates that the need for
      nutrition promotion is substantial. A variety of interventions have improved food
      intake and health of participants, although most programs are provided at a
      tertiary prevention level. Nutrition screening can help to identify in a timely
      manner those older adults who may benefit from limited services and which
      secondary prevention activities need to be increased. Nutrition promotion policy
      is currently lacking for older adults in Canada and is an important barrier to
      improving food intake in this growing segment of the population.

PMID- 18059572
TI  - Exercise, aging, and cancer.
AB  - Cancer is a common disease that affects over 150 000 Canadians every year. About
      78% of all cancers are diagnosed in adults aged 60 years and older. Improved
      survival rates for cancer survivors have brought lifestyle and quality of life
      issues to the forefront. In other chronic disease populations, exercise is
      considered a foundational health behavior; however, the benefits of exercise in
      cancer survivors are only beginning to be described. Moreover, what little is
      known about exercise in cancer survivors has been derived largely from research
      on middle-aged survivors. In the present article, we review the literature on
      exercise, aging, and cancer. Our review shows that very few studies have examined
      exercise in older cancer survivors or have approached the topic from an aging
      perspective. The limited research that is available suggests that, compared with
      middle-aged cancer survivors, older cancer survivors: (i) derive similar benefits
      from exercise, (ii) have lower exercise participation rates, (iii) have more
      difficulty adhering to an exercise program, and (iv) have different determinants
      of exercise motivation and behavior. We end by offering some future research
      directions that may help generate important new exercise knowledge in this
      underserved cancer survivor population.

PMID- 18059573
TI  - Inflammation, obesity, and fatty acid metabolism: influence of n-3
      polyunsaturated fatty acids on factors contributing to metabolic syndrome.
AB  - Metabolic syndrome (MetS) comprises an array of metabolic risk factors including
      abdominal obesity, dyslipidemia, hypertension, and glucose intolerance.
      Individuals with MetS are at elevated risk for diabetes and cardiovascular
      disease. Central to the etiology of MetS is an interrelated triad comprising
      inflammation, abdominal obesity, and aberrations in fatty acid metabolism,
      coupled with the more recently recognized changes in metabolism during the
      postprandial period. We review herein preliminary evidence regarding the role of
      dietary n-3 polyunsaturated fatty acids in modulating each of the components of
      the triad of adiposity, inflammation, and fatty acid metabolism, with particular
      attention to the role of the postprandial period as a contributor to the
      pathophysiology of MetS.

PMID- 18059574
TI  - Type 2 diabetes mellitus, resistance training, and innate immunity: is there a
      common link?
AB  - Type 2 diabetes mellitus is a serious chronic disease that is very prevalent in
      the developed world. The etiology of this disease is not well understood.
      Recently, the role of the innate immune system in the pathogenesis of type 2
      diabetes and its complications has received a great deal of attention. Cytokines,
      acute phase proteins, and phagocytes have been implicated in this model.
      Resistance training has known benefits in type 2 diabetic patients and older
      adults, such as improved insulin action, insulin sensitivity, fasting blood
      glucose and insulin, and glucose tolerance levels. Actions of pro-inflammatory
      mediators linked to dysregulated innate immune activity have been associated with
      type 2 diabetes. The immunomodulatory effects of exercise, and in particular
      approaches such as resistance training, may provide a strategy to counter these
      pro-inflammatory effectors. However, the effects of resistance training on innate
      immunity have not been studied extensively in adults with type 2 diabetes or in
      older adults who are at increased risk for development of type 2 diabetes. This
      review discusses the possibility that resistance training may have positive
      effects on innate immunity in this population and so may provide benefits in
      addition to improving strength and functional abilities. In particular, the
      potential of resistance training to modulate pro-inflammatory parameters
      associated with type 2 diabetes, as a strategy that could provide multiple
      beneficial health outcomes, is addressed.

PMID- 18059575
TI  - Differences in efficiency between trained and recreational cyclists.
AB  - Controversy still exists in the literature as to whether cycling experience
      affects gross mechanical efficiency (GME). The aim of this study was to identify
      differences in efficiency between trained and untrained cyclists. Thirty-two
      participants, 16 trained (mean+/-SD: age, 33+/-4 y; height, 1.76+/-0.05 m; mass
      75+/-10 kg; Wmax, 421+/-38 W; maximal oxygen uptake, 62.6+/-7.30 mL.kg(-1).min(
      1)) and 16 untrained (22+/-3 y, 175+/-0.06 m, 76+/-10 kg, 292+/-34 W, 42.6+/-7.80
      mL.kg(-1).min(-1)), performed two tests of cycling efficiency. One was at the
      relative workloads of 50% and 60% Wmax and the other was at a fixed workload of
      150 W using an electrically braked cycle ergometer. Cadence was maintained at the
      cyclist's preferred rate throughout. All workloads lasted 10 min with data
      sampling in the final 3 min. GME was calculated from the gas data. GME was found
      to be significantly higher in the trained cyclists across all workloads (+1.4%;
      p=0.03). At workloads of 60% Wmax GME was significantly lower than work at 150 W
      (-0.8%; p=0.04), but not significantly different from 50% Wmax. These results
      show that differences do exist between trained and untrained cyclists,
      illustrating that training experience is a factor that warrants further
      investigation.

PMID- 18059576
TI  - Effects of 22 degrees C muscle temperature on voluntary and evoked muscle
      properties during and after high-intensity exercise.
AB  - The purpose of this study was to investigate the effect of 22 degrees C local
      muscle temperature of intact human plantar flexors performing fatiguing
      contractions on evoked and voluntary contractile properties before and after
      fatigue. Twelve subjects were tested on plantar flexor voluntary torque, percent
      muscle activation derived from twitch interpolation, integrated electromyographic
      (iEMG) activity, and evoked torque and temporal characteristics of maximal twitch
      and tetanic stimulations before fatigue and 1, 5, and 10 min after intermittent,
      high-intensity, isometric fatigue under both normothermic and hypothermic
      conditions. Hypothermic and normothermic changes between time points were
      analysed by repeated-measures analysis of variance. Normothermic fatigue induced
      small to large effects (Cohen's d: 0.29-3.06) on voluntary and evoked contractile
      properties, whereas most effects of unfatigued hypothermia were limited to rate
      dependent processes (Cohen's d: 0.78-1.70). Most tetanic properties were
      potentiated 1 min after normothermic fatigue, but remained unchanged by
      hypothermic fatigue, resulting in significant differences between the two
      conditions. Soleus iEMG significantly declined 1 min after normothermic fatigue (
      29%), but not after hypothermic fatigue. Twitch torque was potentiated by 29% one
      minute after fatigue while normothermic, but was potentiated by 46% while
      hypothermic; rate of twitch torque development and time to peak twitch were
      potentiated by 39% and 10% while normothermic, but 89% and 28% while hypothermic.
      Although voluntary contractile properties are generally impaired soon after
      normothermic fatigue, most were not after hypothermic fatigue. Furthermore,
      evoked contractile properties were generally higher 1 min after hypothermic
      fatigue. We conclude that the hypothermic condition slows the recovery of
      potentiated evoked contractile properties back to baseline values.

PMID- 18059577
TI  - Effect of in-season creatine supplementation on body composition and performance
      in rugby union football players.
AB  - Rugby union football requires muscular strength and endurance, as well as aerobic
      endurance. Creatine supplementation may enhance muscular performance, but it is
      unclear if it would interfere with aerobic endurance during running because of
      increased body mass. The purpose of this study was to determine if creatine
      supplementation during 8 weeks of a season of rugby union football can increase
      muscular performance, without negatively affecting aerobic endurance. Rugby union
      football players were randomized to receive 0.1 g.kg(-1).d(-1) creatine
      monohydrate (n=9) or placebo (n=9) during 8 weeks of the rugby season. Players
      practiced twice per week for approximately 2 h per session and played one 80 min
      game per week. Before and after the 8 weeks, players were measured for body
      composition (air displacement plethysmography), muscular endurance (number of
      repetitions at 75% of one repetition maximum (1 RM) for bench press and leg
      press), and aerobic endurance (Leger shuttle-run test with 1 min stages of
      progressively increasing speed). There were time main effects for body mass (
      0.7+/-0.4 kg; p=0.05), fat mass (-1.9+/-0.8 kg; p<0.05), and a trend for an
      increase in lean tissue mass (+1.2+/-0.5 kg; p=0.07), with no differences between
      groups. The group receiving creatine supplementation had a greater increase in
      the number of repetitions for combined bench press and leg press tests compared
      with the placebo group (+5.8+/-1.4 vs. +0.9+/-2.0 repetitions; p<0.05). There
      were no changes in either group for aerobic endurance. Creatine supplementation
      during a rugby union football season is effective for increasing muscular
      endurance, but has no effect on body composition or aerobic endurance.

PMID- 18059578
TI  - The effect of pre-test carbohydrate ingestion on the anaerobic threshold, as
      determined by the lactate-minimum test.
AB  - The purpose of this study was to investigate the effect of pre-test carbohydrate
      (CHO) ingestion on anaerobic-threshold assessment using the lactate-minimum test
      (LMT). Fifteen competitive male distance runners capable of running 10 km in 33.5
      43 min were used as subjects. LMT was performed following CHO (2x300 mL, 7%
      solution) or comparable placebo (Pl) ingestion, in a double-blind, randomized
      order. The LMT consisted of two high-intensity 1 min treadmill runs (17-21 km.h(
      1)), followed by an 8 min recovery period. Subsequently, subjects performed 5 min
      running stages, incremented by 0.6 km.h(-1) and separated by 1 min blood-sampling
      intervals. Tests were terminated after 3 consecutive increases in blood-lactate
      concentration ([La]) had been observed. Finger-tip capillary blood was sampled
      for [La] and blood-glucose determination 30 min before the test's onset, during
      the recovery phase following the 2 high-intensity runs, and following each of the
      subsequent 5 min stages. Heart rate (HR) and rating of perceived exertion (RPE)
      were recorded after each stage. The lactate-minimum speed (LMS) was determined
      from the individual [La]-velocity plots and was considered reflective of the
      anaerobic threshold. Pre-test CHO ingestion had no effect on LMS (13.19+/-1.12
      km.h(-1) vs. 13.17+/-1.08 km.h(-1) in CHO and Pl, respectively), nor on [La] and
      glucose concentration at that speed, or on HR and RPE responses. Pre-test CHO
      ingestion therefore does not affect LMS or the LMT-estimated anaerobic threshold.

PMID- 18059579
TI  - Ethnic differences in adiposity and body composition: the First Nations bone
      health study.
AB  - The purpose of this study was to compare patterns of adiposity and soft tissue
      composition in First Nations and white Canadian women. A population-based cross
      sectional study was performed. A random age-stratified sample of 206 urban First
      Nations women and 177 white women was recruited. Soft tissue composition was
      analyzed with dual-energy X-ray absorptiometry. Analysis of covariance (ANCOVA)
      models were used to assess ethnicity in models that adjusted for body mass, body
      mass index (BMI), and socio-demographic factors. Obesity (BMI>or=30.0 kg/m2) was
      more common in First Nations women (48.1%) than in white women (36.2%, Fisher's
      exact test p=0.012). Mean trunk fat tissue mass fraction and total body fat mass
      fraction (as a percent of soft tissue) were greater in First Nations women than
      in white women (p<0.0001). Trunk lean tissue was also greater in First Nations
      women (p=0.027), but total body lean tissue was similar. The mean trunk adiposity
      index was strongly related to ethnicity (First Nations +0.5%+/-2.5% versus white 
      1.7%+/-2.6%, p<0.0001). Preferential fat accumulation in the trunk of First
      Nations women persisted after adjustment for body mass, BMI, and other socio
      demographic variables (p<0.0001). First Nations women differ from white women in
      terms of fat and lean tissue mass and distribution. First Nations women had a
      preferential increase in trunk fat and this may contribute to high reported rates
      of diabetes, metabolic syndrome, and cardiovascular events.

PMID- 18059580
TI  - New oral fat tolerance tests feature tailoring of the polyunsaturated/saturated
      fatty acid ratio to elicit a specific postprandial response.
AB  - The impact of dietary fat on postprandial metabolic biomarkers for obesity
      related chronic diseases, such as type-2 diabetes and cardiovascular disease, has
      received significant recent attention. However, there is no standard method to
      evaluate the postprandial response to dietary fat alone. Our goals were to
      develop a novel oral fat tolerance test (OFTT) consisting solely of emulsified
      lipids tailored for specific fatty acid compositions and to evaluate the
      functionality of specific ratios of polyunsaturated/saturated fatty acid (P/S)
      loading on postprandial triacylglyceride (TAG) concentrations. Two OFTTs of
      emulsified lipids were prepared with specific P/S ratios of 0.2 and 2.0. Physical
      characteristics of the fat blends, including TAG composition, melting point, and
      emulsion droplet size were quantified. Healthy, older (age>45 y) men (n=8)
      underwent an 8 h postprandial study wherein they received the OFTT treatment
      (either the P/S ratio of 0.2 or 2.0), with a total lipid load of 1 g/kg subject
      body mass. All subjects received both treatments separated by at least 1 week.
      Both the P/S 0.2 and 2.0 OFTT significantly elevated (p<0.05) blood TAG and free
      fatty acid concentrations for 8 h without increasing blood glucose or serum
      insulin concentrations. The predominant fatty acids contained in the P/S 0.2
      (palmitic acid, 16:0) and 2.0 (linoleic acid, 18:2(n-6)) OFTT blends were
      significantly elevated in the blood (p<0.05) during their respective postprandial
      periods. We concluded that blood TAGs are elevated in a specific pattern through
      the administration of novel OFTTs with specific P/S blends without eliciting an
      insulin or glucose response.

PMID- 18059581
TI  - Specific inspiratory muscle warm-up enhances badminton footwork performance.
AB  - The effects of inspiratory muscle (IM) warm-up on IM function and on the maximum
      distance covered in a subsequent incremental badminton-footwork test (FWmax) were
      examined. Ten male badminton players were recruited to perform identical tests in
      three different trials in a random order. The control trial did not involve an IM
      warm-up, whereas the placebo and experimental trials did involve an IM warm-up
      consisting of two sets of 30-breath manoeuvres with an inspiratory pressure
      threshold load equivalent to 15% (PLA) and 40% (IMW) maximum inspiratory mouth
      pressure, respectively. In the IMW trial, IM function was improved with 7.8%+/
      4.0% and 6.9%+/-3.5% increases from control found in maximal inspiratory pressure
      at zero flow (P0) and maximal rate of P0 development (MRPD), respectively
      (p<0.05). FWmax was enhanced 6.8%+/-3.7%, whereas the slope of the linear
      relationship of the increase in the rating of perceived breathlessness for every
      minute (RPB/min) was reduced (p<0.05). Reduction in blood lactate ([La-]b)
      accumulation was observed when the test duration was identical to that of the
      control trial (P<0.05). In the PLA trial, no parameter was changed from control.
      For the changes (Delta) in parameters in IMW (n=10), negative correlations were
      found between DeltaP0 and DeltaRPB/min (r2=0.58), DeltaMRPD and DeltaRPB/min
      (r2=0.48), DeltaRPB/min, and DeltaFWmax (r2=0.55), but not between Delta[La-]b
      accumulation and DeltaFWmax. Such findings suggest that the IM-specific warm-up
      improved footwork performance in the subsequent maximum incremental badminton
      footwork test. The improved footwork was partly attributable to the reduced
      breathless sensation resulting from the enhanced IM function, whereas the
      contribution of the concomitant reduction in [La-]b accumulation was relatively
      minor.

PMID- 18059582
TI  - Relationship between insulin sensitivity and the triglyceride-HDL-C ratio in
      overweight and obese postmenopausal women: a MONET study.
AB  - The objective of this cross-sectional study was to examine the relationship
      between the triglyceride-HDL-cholesterol ratio (TG:HDL-C) and insulin sensitivity
      in overweight and obese sedentary postmenopausal women. The study population
      consisted of 131 non-diabetic overweight and obese sedentary postmenopausal women
      (age; 57.7+/-5.0 y; body mass index (BMI), 32.2+/-4.3 kg/m2). Subjects were
      characterized by dividing the entire cohort into tertiles based on the TG:HDL-C
      (T1<0.86 vs. T2=0.86 to 1.35 vs. T3>1.35, respectively). We measured (i) insulin
      sensitivity (using the hyperinsulinenic-euglycemic clamp and homeostasis model
      assessment (HOMA)), (ii) body composition (using dual-energy X-ray
      absorptiometry), (iii) visceral fat (using computed tomography), (iv) plasma
      lipids, C-reactive protein, 2 h glucose concentration during an oral glucose
      tolerance test (2 h glucose), as well as fasting glucose and insulin, (v) peak
      oxygen consumption, and (vi) lower-body muscle strength (using weight training
      equipment). Significant correlations were observed between the TG:HDL-C and the
      hyperinsulinemic-euglycemic clamp (r=-0.45; p<0.0001), as well as with HOMA
      (r=0.42; p<0.0001). Moreover, the TG:HDL-C significantly correlated with lean
      body mass, visceral fat, 2 h glucose, C-reactive protein, and muscle strength.
      Stepwise regression analysis showed that the TG:HDL-C explained 16.4% of the
      variation in glucose disposal in our cohort, which accounted for the greatest
      source of unique variance. Other independent predictors of glucose disposal were
      2 h glucose (10.1%), C-reactive protein (CRP; 7.6%), and peak oxygen consumption
      (5.8%), collectively (including the TG:HDL-C) explaining 39.9% of the unique
      variance. In addition, the TG:HDL-C was the second predictor for HOMA, accounting
      for 11.7% of the variation. High levels of insulin sensitivity were associated
      with low levels of the TG:HDL-C. In addition, the TG:HDL-C was a predictor for
      glucose disposal rates and HOMA values in our cohort of overweight and obese
      postmenopausal women.

PMID- 18059583
TI  - Proanthocyanidin promotes free radical-scavenging activity in muscle tissues and
      plasma.
AB  - The present study was carried out to clarify the effect of oral administration of
      proanthocyanidin (PA) on radical-scavenging activity in muscle and plasma using
      electron spin resonance (ESR). Eight-week-old male Wistar rats were orally
      administered with 3 doses per day of 1 mL of 0.05% (PA0.05), 0.5% (PA0.5) or 5%
      (PA5) PA for 1 week. Control animals received the same volume of distilled water.
      We also examined the effect of a single dose of 0.5% PA. Blood and muscle were
      collected from rats 1 h after the final administration. Scavenging activity
      against superoxide anions in the plasma and m. soleus (Sol), m. plantaris (Pla),
      deep and surface areas of the m. gastrocnemius (GasD and GasS, respectively) and
      myocardium (Hrt) was determined using ESR with the spin trap, 5,5-dimethyl-1
      pyrroline-N-oxide The scavenging activity in plasma for all groups given PA was
      34%-44% higher than the control (p<0.05). The scavenging activity in Hrt, Sol and
      GasD increased by up to 50% compared with the control and tended to increase
      depending on the dose of PA (p<0.05). The impact of a single dose of PA was
      undetectable in all tissues. These results suggested that 1 week of oral PA
      improves the radical-scavenging activity in both plasma and muscle, especially in
      highly oxidative muscle. A single dose of PA was insufficient to improve the
      antioxidative capacity of muscle tissues.

PMID- 18059584
TI  - Dietary intake, capillary blood glucose, and activity level of activity
      restricted, hospitalized, pregnant women in the third trimester: a pilot study.
AB  - Activity restriction in hospital is commonly prescribed by care providers to
      decrease the incidence of maternal or fetal morbidity in high-risk pregnancies.
      The purpose of this pilot descriptive study was to collect preliminary data on
      dietary intake, capillary blood glucose concentrations, and activity level in
      high-risk, activity-restricted, pregnant women in the third trimester of
      pregnancy. Dietary food intake records, capillary blood glucose, and daily
      pedometer step totals were investigated in 20 activity-restricted women over 7
      consecutive days in hospital. Subjects were asked to collect hospital meal
      tickets, as well as record any additional items not provided by the hospital in a
      dietary log each day. Capillary blood glucose was collected every morning
      (fasting) as well as 1 h after breakfast (post-prandial) using a glucometer.
      Subjects wore a pedometer 24 h/d, and recorded step totals 4 times daily in a
      pedometer log. In the analysis, average energy and macronutrient intakes met
      dietary reference intake (DRI) recommendations, as did average intakes of all
      micronutrients, including maternal supplementation. Without supplementation,
      vitamin E and iron intakes were lower (p<0.05) than the DRI recommendations.
      Average fasting (4.6+/-0.5 mmol/L) and post-prandial (7.1+/-1.0 mmol/L) blood
      glucose concentrations in subjects without gestational diabetes (GDM) did not
      exceed Canadian Diabetes Association cut-off values for screening of GDM. The
      mean daily step total of 1579+/-936 was lower than ambulatory third-trimester
      women (6495+/-2282 steps; p<0.001). Results from this pilot study suggest that
      with maternal supplementation, these activity-restricted, hospitalized, pregnant
      women were meeting dietary recommendations, and did not have elevated capillary
      blood glucose. However, given the severity of activity restriction, these women
      may be at risk for consequences of extreme inactivity.

PMID- 18059585
TI  - Rat hindlimb unloading down-regulates insulin like growth factor-1 signaling and
      AMP-activated protein kinase, and leads to severe atrophy of the soleus muscle.
AB  - Inactivity is known to induce muscle atrophy, which is associated with insulin
      and insulin-like growth factor-1 (IGF-1) resistance, but the associated
      mechanisms remain poorly defined. The hindlimb unloading model has been used to
      reduce muscle activity. The objective of this study was to show the effect of
      hindlimb unloading on IGF-1 signaling and AMP-activated protein kinase (AMPK)
      activity in rat soleus and extensor digitorum longus (EDL) muscles. Twelve 7-week
      old male Sprague-Dawley rats were assigned to 2 treatments: (i) rats without
      hindlimb unloading (Con) and (ii) rats with hindlimb unloading (Unload). After 2
      weeks of treatment, the soleus and EDL muscles were dissected and used for
      biochemical analyses. Hindlimb unloading induced severe muscle atrophy in soleus
      muscle (0.122+/-0.007 g for Con vs. 0.031+/-0.004 g for Unload, p<0.01), but only
      slight atrophy in EDL muscle. The phosphorylation of AMPK (p<0.05) and its
      downstream substrate, acetyl-CoA carboxylase (ACC) (p<0.01) were reduced in
      soleus muscle due to unloading. The concentration of insulin receptor substrate-1
      (IRS-1) and phosphorylation of IRS-1 at Ser636-639 and Ser789 were also reduced.
      Downstream IGF-1 signaling was downregulated in Unload rats. A reduction in IGF-1
      concentration in unloaded soleus muscle was also observed. A slight reduction in
      AMPK activity and IGF-1 signaling were observed in EDL muscle. Since AMPK
      controls the sensitivity of IGF-1 signaling through phosphorylation at Ser789,
      the reduction in AMPK activity is expected to reduce the response of downstream
      IGF-1 signaling to IGF-1; this, in combination with reduced IGF-1 concentration,
      might be responsible for the severe muscle atrophy observed in unloaded soleus
      muscle.

PMID- 18059586
TI  - Gender comparisons of exercise-induced oxidative stress: influence of antioxidant
      supplementation.
AB  - The purpose of this study was to determine the influence of gender and
      antioxidant supplementation on exercise-induced oxidative stress. Twenty-five men
      and 23 women ran for 30 min at 80% VO2 max, once before and once after 2 weeks of
      supplementation, and again after a 1-week wash-out period. Subjects were randomly
      assigned to either placebo (P), antioxidant (A: 400 IU vitamin E+1 g vitamin C),
      or a fruit and vegetable powder (FV) treatment. Blood was obtained at rest and
      immediately after exercise. Before supplementation, women had higher resting
      reduced glutathione, total glutathione, and plasma vitamin E compared with men.
      With both A and FV supplementations, plasma vitamin E gender differences
      disappeared. Protein carbonyls, oxidized glutathione, and malondialdehyde all
      increased similarly for both genders in response to exercise. Both A and FV
      attenuated the reduced glutathione decrease and the oxidized glutathione and
      protein carbonyls increase compared with P, with no gender differences. 8
      hydroxydeoxyguanosine was lower with treatment A compared with FV and P only for
      men. Plasma vitamin C increased 39% (A) and 21% (FV) compared with P. These data
      indicate that women have higher resting antioxidant levels than men. Markers of
      oxidative stress increased similarly in both genders in response to exercise of
      similar intensity and duration. Two weeks of antioxidant supplementation can
      attenuate exercise-induced oxidative stress equally in both genders.

PMID- 18059587
TI  - Minimal whey protein with carbohydrate stimulates muscle protein synthesis
      following resistance exercise in trained young men.
AB  - Whey protein is a supplemental protein source often used by athletes,
      particularly those aiming to gain muscle mass; however, direct evidence for its
      efficacy in stimulating muscle protein synthesis (MPS) is lacking. We aimed to
      determine the impact of consuming whey protein on skeletal muscle protein
      turnover in the post-exercise period. Eight healthy resistance-trained young men
      (age=21+/-1 .0 years; BMI=26.8+/-0.9 kg/m2 (means+/-SE)) participated in a double
      blind randomized crossover trial in which they performed a unilateral leg
      resistance exercise workout (EX: 4 sets of knee extensions and 4 sets of leg
      press; 8-10 repetitions/set; 80% of maximal), such that one leg was not exercised
      and acted as a rested (RE) comparator. After exercise, subjects consumed either
      an isoenergetic whey protein plus carbohydrate beverage (WHEY: 10 g protein and
      21 g fructose) or a carbohydrate-only beverage (CHO: 21 g fructose and 10 g
      maltodextran). Subjects received pulse-tracer injections of L-[ring
      2H5]phenylalanine and L-[15N]phenylalanine to measure MPS. Exercise stimulated a
      rise in MPS in the WHEY-EX and CHO-EX legs, which were greater than MPS in the
      WHEY-RE leg and the CHO-RE leg (all p<0.05), respectively. The rate of MPS in the
      WHEY-EX leg was greater than in the CHO-EX leg (p<0.001). We conclude that a
      small dose (10 g) of whey protein with carbohydrate (21 g) can stimulate a rise
      in MPS after resistance exercise in trained young men that would be supportive of
      a positive net protein balance, which, over time, would lead to hypertrophy.

PMID- 18059588
TI  - Effect of timing of energy and carbohydrate replacement on post-exercise insulin
      action.
AB  - The nutritional environment surrounding an exercise bout modulates post-exercise
      insulin action. The purpose of this study was to determine how timing energy and
      carbohydrate replacement proximate to an exercise bout influences exercise
      enhanced insulin action. To create an appropriate baseline, sensitivity to
      insulin was reduced in 9 healthy young men (n=6) and women (n=3) by 2 days of
      energy surplus and detraining. Then, insulin action (glucose uptake per unit
      plasma insulin) was assessed by stable isotope dilution during a continuous
      glucose infusion 12 h after a standardized meal under 4 conditions. In 3
      conditions, the meal replaced the energy and carbohydrate expended during an
      exercise bout (62.9+/-2.8 min cycle ergometry at 65% VO2 peak followed by ten 30
      s sprints). The meal was given before (Pre), immediately after (ImmPost), or 3 h
      after exercise (Delay). The 4th condition was a no-exercise control (Control).
      Data were analyzed using linear mixed-effects models with planned contrasts.
      Relative to Control, insulin action increased by 22% in Pre (p=0.05), 44% in
      ImmPost (p<0.01), and 19% in Delay (p=0.09). Non-oxidative disposal was higher,
      and oxidative disposal was lower in ImmPost relative to Control and Pre (p<0.05).
      Hepatic glucose production was suppressed by the infusion to a greater extent in
      Pre and Delay (76.9%+/-8.8% and 81.2%+/-4.7%) compared with ImmPost (64.7%+/
      10.0%). A bout of exercise enhances insulin action even when expended energy and
      carbohydrate are replaced. Further, timing of energy and carbohydrate consumption
      subtly modulates the effectiveness of exercise to enhance insulin action.

PMID- 18059589
TI  - Effect of pharmacological lowering of plasma urate on exercise-induced oxidative
      stress.
AB  - Urate is a metabolic end product of purine metabolism that contributes about 66%
      of the antioxidant capacity of plasma. The objective of this study was to
      evaluate the importance of plasma urate as an antioxidant using pharmacological
      lowering and examining the impact on plasma antioxidant capacity and oxidative
      stress after intense exercise. Fifteen subjects ran for 45 min at approximately
      80% VO2 max under the influence of probenecid (1 g/d) (PRO) or placebo (PLA) in a
      double-blind, crossover design. Blood samples obtained at baseline, pre-exercise,
      and immediately post-exercise were analyzed for F2-isoprostanes, lipid
      hydroperoxides (LHs), ferric-reducing ability of plasma (FRAP), urate, ascorbate
      (AA), and nitrite. A 2 (group)x2 (time) repeated-measures analysis of variance
      (ANOVA), one-way ANOVA, Tukey-Kramer multiple comparison tests, and Student's t
      tests were used for statistical analysis. PRO exhibited lowered urate and FRAP
      compared with baseline (p<or=0.05), and group effects existed for the exercise
      trials (p=0.023 and p<or=0.001, respectively) versus PLA. F2-isoprostanes,
      nitrite, and AA were increased after exercise (p=0.004, p=0.001, and p=0.003,
      respectively), but the pattern of change was not different between treatments.
      This study indicates that plasma markers of exercise-induced oxidative stress
      were not affected by below-normal physiological concentrations of urate and a
      diminished antioxidant capacity within the plasma compartment.

PMID- 18059590
TI  - The effects of whole-body vibration on upper- and lower-body EMG during static
      and dynamic contractions.
AB  - Whole-body vibration (WBV) training uses a vertically oscillating platform and
      reports suggest that this perturbation elicits reflexive muscle contractions that
      augment muscle activity and contribute to increased strength. No WBV study has
      measured both upper- and lower-body muscle activation. The purpose of this study
      was to determine the optimal WBV stimulus (frequency x amplitude) to increase
      electromyography (EMG) in upper- and lower-body muscles for three distinctive
      unloaded actions: isometric semi-squat, dynamic leg squats, and static and
      dynamic bilateral bicep curls. Surface EMG was measured for the vastus lateralis
      (VL), biceps femoris (BF), biceps brachii (BB), and triceps brachii (TB) in 10
      recreationally active male university students (24.4+/-2.0 years; mean+/-SD) when
      WBV was administered at 2 and 4 mm and at 25, 30, 35, 40, and 45 Hz. EMG changes
      are reported as the difference between WBV and no WBV EMG root mean square
      expressed as a percentage of maximum voluntary exertion (%MVE). In static semi
      squat, WBV increased muscle activity 2.9%-6.7% in the VL and 0.8%-1.2% in the BF.
      During dynamic squatting, WBV increased muscle activity in the VL by 3.7%-8.7%
      and in the BF by 0.4%-2.0%. In a static biceps curl, WBV had no effect on BB EMG,
      but did increase TB activity 0.3%-0.7%. During dynamic biceps curls, WBV
      increased BB EMG activity by 0.6%-0.8% and TB activity by 0.2%-1.0%. The higher
      WBV amplitude (4 mm) and frequencies (35, 40, 45 Hz) resulted in the greatest
      increases in EMG activity.

PMID- 18059591
TI  - Time-course of changes in cardiac function during recovery after acute exercise.
AB  - Exercise-induced cardiac dysfunction (EICD) has been observed immediately
      following exhaustive exercise in trained individuals, but limited and conflicting
      data are available regarding EICD in a previously untrained population days after
      an exhaustive exercise bout. The purpose of this study was to examine the effects
      of a single bout of acute exercise on cardiac function during the 72 h after
      exercise and identify potential contributing mechanisms. After completing an
      acute exercise bout on a motorized treadmill (25 m/min, 5% grade, 60 min), rats
      were sacrificed immediately, 24 h, 48 h, or 72 h after the exercise bout. At the
      scheduled time of sacrifice, hearts were isolated and perfused for determination
      of ex vivo cardiac function, and examined for malondialdehyde (MDA), a lipid
      peroxidation index, and antioxidant potential (AOP). During the 48 h post
      exercise, left ventricular developed pressure decreased by 30%, dP/dtmax declined
      by 37%, and dP/dtmin showed a 34% decrease (p<0.05). By 72 h, cardiac function
      had returned to control levels. MDA was increased immediately after the exercise
      bout and at the 24 and 48 h intervals (p<0.05). Conversely, AOP progressively
      decreased at the 24 and 48 h intervals. As with cardiac function, MDA and AOP had
      returned to control levels by 72 h post-exercise. These data indicate that a
      single bout of prolonged, moderately intense exercise performed by previously
      sedentary rats impaired cardiac function for up to 48 h. This decrement in
      cardiac function was associated with increased lipid peroxidation and decreased
      antioxidant potential.

PMID- 18059592
TI  - The physical activity counselling (PAC) randomized controlled trial: rationale,
      methods, and interventions.
AB  - Primary care is a promising venue to build patient motivation and confidence to
      increase physical activity (PA). Physician PA counselling has demonstrated some
      success; however, maintenance of behaviour change appears to require more
      intensive interventions. In reality, most physicians do not have the necessary
      training nor the time for this type of counselling. The purpose of this paper is
      to outline the rationale, methods, and interventions for the ongoing physical
      activity counselling (PAC) randomized controlled trial (RCT), which aims to
      assess the impact of integrating a PA counsellor into a primary care practice.
      This RCT has 2 arms: (i) brief PA counselling (2-4 min) from a health care
      provider and (ii) brief PA counselling+intensive PA counselling from a PA
      counsellor (3 months). The impact of this intervention is being evaluated using
      the comprehensive RE-AIM framework. One hundred twenty insufficiently active
      adult patients, aged 18 to 69 y and recruited during regular primary care visits
      have been randomized. Dependent measures include psychological mediators, PA
      participation, quality of life, and physical and metabolic outcomes. The PAC
      project represents an innovative, theoretically-based approach to promoting PA in
      primary care, focusing on psychological mediators of change. We anticipate that
      key lessons from this study will be useful for shaping future public health
      interventions, theories, and research.

PMID- 18059593
TI  - Glutamine and carbohydrate supplements reduce ammonemia increase during endurance
      field exercise.
AB  - Blood ammonia concentration increases during endurance exercise and has been
      proposed as a cause for both peripheral and central fatigue. We examined the
      impact of glutamine and (or) carbohydrate supplementation on ammonemia in high
      level runners. Fifteen men in pre-competitive training ran 120 min (approximately
      34 km) outdoors on 4 occasions. On the first day, the 15 athletes ran without the
      use of supplements and blood samples were taken every 30 min. After that, each
      day for 4 d before the next 3 exercise trials, we supplemented the athletes'
      normal diets in bolus with carbohydrate (1 g.kg(-1).d(-1)), glutamine (70 mg.kg(
      1).d(-1)), or a combination of both in a double-blind study. Blood ammonia level
      was determined before the run and every 30 min during the run. During the control
      trial ammonia increased progressively to approximately 70% above rest
      concentration. Following supplementation, independent of treatment, ammonia was
      not different (p>0.05) for the first 60 min, but for the second hour it was lower
      than in the control (p<0.05). Supplementation in high-level, endurance athletes
      reduced the accumulation of blood ammonia during prolonged, strenuous exercise in
      a field situation.

PMID- 18059594
TI  - Revised clearance for participation in physical activity: greater screening
      responsibility for qualified university-educated fitness professionals.
AB  - For many individuals, pre-participation clearance using the PAR-Q and the PARmed
      X has become a barrier to adopting a physically active lifestyle. An extensive
      project is therefore planned to reduce the number of medical referrals from the
      PAR-Q and to revise the PARmed-X so that it becomes more effective, user
      friendly, and evidence based. The entire process will likely require 3 years to
      complete; therefore, as an interim solution, we propose giving greater pre
      participation screening responsibility to qualified university-educated fitness
      professionals. The highest level of professional fitness qualification in Canada
      is the Canadian Society for Exercise Physiology Certified Exercise Physiologist;
      the requirements for this certification are such that it could serve as a model
      allowing other countries that use the PAR-Q to develop similarly qualified
      university-educated fitness professionals who could also be entrusted with
      greater pre-participation screening responsibility.

PMID- 18059595
TI  - Resistance exercise: good for more than just Grandma and Grandpa's muscles.
AB  - Progressive resistance training promotes strength gains in both the young and the
      aged. Importantly, gains in strength in aged persons are, with the appropriate
      duration, intensity, and progression, not simply due to neuromuscular mechanisms,
      but also encompass muscle fibre hypertrophy. Critically, the resistance exercise
      induced changes in aged skeletal muscle are associated with numerous health
      benefits, the most obvious of which are the gains in strength and, with the
      correct training program, power; as a result, functional independence is improved
      and the risk for falls is apparently reduced. Aside from the well-documented
      effects of resistance training on strength and power, a body of research is now
      beginning to emerge that shows resistance exercise also promotes metabolic
      health. This is crucial information, since it effectively highlights an
      underappreciated aspect of resistance exercise. Specifically, resistance exercise
      not only promotes strength gains, but also reduces risk for diabetes and
      cardiovascular disease. The benefits of resistance exercise do not end at
      metabolic health, however, and "spill over" into many other realms. In fact,
      resistance exercise programs have been shown to reduce participants' use of the
      health care system. Viewed collectively, the multiple benefits of resistance
      exercise represent an attractive option for our aging population to enhance and
      maintain their health from a number of perspectives that are not achievable
      through pharmacological intervention or with solely aerobic-based exercise.

PMID- 18059596
TI  - Prohibition of artificial hypoxic environments in sports: health risks rather
      than ethics.
AB  - There is actual debate on a recent position of the World Anti-Doping Agency
      (WADA), which has cautiously refrained from banning hypoxic tents and intends to
      monitor their health risk. Regardless of teleological and deontological concepts,
      we highlight that the health risks inherent to the widespread use of these
      artificial performance-enhancing devices would make them as unsafe as other forms
      of blood doping.

PMID- 18059601
TI  - Ventilatory constraints and dyspnea during exercise in chronic obstructive
      pulmonary disease.
AB  - Dyspnea (respiratory difficulty) and activity limitation are the primary symptoms
      of chronic obstructive pulmonary disease (COPD) and progress relentlessly as the
      disease advances, contributing to reduced quality of life. In COPD, the
      mechanisms of dyspnea are multifactorial, but abnormal dynamic ventilatory
      mechanics are believed to play a central role. In flow-limited patients with
      COPD, dynamic lung hyperinflation (DH) occurs during exercise and has serious
      sensory and mechanical consequences. In several studies, indices of DH strongly
      correlate with ratings of dyspnea intensity during exercise, and strategies that
      reduce resting hyperinflation (either pharmacological or surgical) consistently
      result in reduced exertional dyspnea. The mechanisms by which DH gives rise to
      exertional dyspnea and exercise intolerance are complex, but recent mechanistic
      studies suggest that DH-induced inspiratory muscle loading, restriction of tidal
      volume expansion during exercise, and consequent neuromechanical uncoupling of
      the respiratory system are key components. This review examines the specific
      derangements of ventilatory mechanics that occur in COPD during exercise and
      attempts to provide a mechanistic rationale for the attendant respiratory
      discomfort and activity limitation.

PMID- 18059602
TI  - Chemical and mechanical adaptations of the respiratory system at rest and during
      exercise in human pregnancy.
AB  - Human pregnancy is characterized by significant increases in ventilatory drive
      both at rest and during exercise. The increased ventilation and attendant
      hypocapnia of pregnancy has been attributed primarily to the stimulatory effects
      of female sex hormones (progesterone and estrogen) on central and peripheral
      chemoreflex drives to breathe. However, recent research from our laboratory
      suggests that hormone-mediated increases in neural (or non-chemoreflex) drives to
      breathe may contribute importantly to the hyperventilation of pregnancy. This
      review challenges traditional views of ventilatory control, and outlines an
      alternative hypothesis of the control of breathing during human pregnancy that is
      currently being tested in our laboratory. Conventional wisdom suggests that
      pregnancy-induced increases in central respiratory motor output command in
      combination with progressive thoraco-abdominal distortion may compromise the
      normal mechanical response of the respiratory system to exercise, increase the
      perception of exertional breathlessness, and curtail aerobic exercise performance
      in otherwise healthy pregnant women. The majority of available evidence suggests,
      however, that neither pregnancy nor advancing gestation are associated with
      reduced aerobic working capacity or increased breathlessness at any given work
      rate or ventilation during exhaustive weight-supported exercise.

PMID- 18059603
TI  - Effects of ageing on muscle O2 utilization and muscle oxygenation during the
      transition to moderate-intensity exercise.
AB  - At the onset of exercise, an increase in muscle and pulmonary O2 consumption is
      met by increases in muscle O2 delivery and muscle O2 extraction. Thus, the study
      of pulmonary O2 uptake kinetics reflects the integrated response between the
      convective and diffusive O2 delivery systems and the muscle metabolic machinery
      (i.e., mitochondrial enzyme activation and provision of acetyl groups to the
      tricarboxcylic acid cycle) to increase muscle O2 consumption. Pulmonary O2 uptake
      kinetics are slowed in older adults compared with young adults and previous
      studies suggest that the slower O2 uptake kinetics may be the result of an age
      associated decline in the ability of older adults to increase O2 delivery to
      active muscles. However, an inherent limitation to understanding the control of
      and limitations to pulmonary O2 uptake kinetics is that it is methodologically
      difficult to examine the adaptation of muscle perfusion and O2 delivery and
      muscle O2 utilization in the muscle microcirculation of active muscles in the
      dynamically exercising human. In this review, we provide an overview of the
      effect of ageing on pulmonary O2 uptake kinetics (reflecting the activation of
      muscle O2 consumption) during the transition to moderate-intensity exercise. Age
      related changes in O2 delivery systems and muscle oxidative capacity are examined
      as potential limitations to pulmonary O2 uptake kinetics. We then review recent
      studies from our laboratory that have investigated the control of pulmonary O2
      uptake kinetics at the level of the muscle microcirculation by examining the
      adaptation of muscle O2 delivery and muscle O2 utilization using near-infrared
      spectroscopy during the transition to exercise in healthy young and older adults.

PMID- 18059604
TI  - Exercise-induced arterial hypoxaemia in active young women.
AB  - Studies examining pulmonary gas exchange during exercise have primarily focused
      on young healthy men, whereas the female response to exercise has received
      limited attention. Evidence is accumulating that the response of the lungs,
      airways, and (or) respiratory muscles to exercise is less than ideal and this may
      significantly compromise oxygen transport in certain groups of otherwise healthy,
      fit, active, male subjects. Women may be even more susceptible to exercise
      induced pulmonary limitations than height-matched men, by virtue of their smaller
      lung volumes, lower maximal expiratory flow rates, and smaller diffusion surface
      areas. We have recently shown that exercise-induced arterial hypoxaemia (EIAH) is
      more prevalent and occurs at relatively lower fitness levels in females than in
      males. Despite this finding, few physiologically based mechanisms have been
      identified to explain why women may be more susceptible to EIAH than men.
      Potential mechanisms of EIAH include relative alveolar hypoventilation,
      ventilation-perfusion inequality, and diffusion limitation. Whether these
      mechanisms are different between sexes remains controversial. The primary purpose
      of this review is to summarize the available data on EIAH in women and to discuss
      potential sex-based mechanisms for gas exchange impairment. Furthermore, we
      discuss unresolved questions dealing with pulmonary system limitations during
      exercise in women.

PMID- 18059606
TI  - The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15.
AB  - Skeletal muscle fibers express several cytokines, including interleukin (IL)-6,
      IL-8, and IL-15. Solid evidence exists that muscular IL-6 and IL-8 are regulated
      by muscle contractions, at both the mRNA and the protein levels. IL-6 increases
      insulin-stimulated glucose disposal and fatty acid oxidation in humans in vivo.
      Both IL-6 and IL-8 are released from working skeletal muscle, but because IL-6
      contributes to the systemic circulation only a small transient net release of IL
      8 is found from working muscle, suggesting that IL-8 may exert its effects
      locally in the muscle. IL-15 is a recently discovered growth factor, which is
      highly expressed in skeletal muscle. Interestingly, although IL-15 has been
      demonstrated as having anabolic effects on skeletal muscle in vitro and in vivo,
      it seems to play a role in reducing adipose tissue mass, and a role for IL-15 in
      muscle-fat cross-talk has been hypothesized. In conclusion, muscle-derived
      cytokines appear to have important roles in metabolism, and exercise plays a role
      in orchestrating the interplay between cytokines and metabolism.

PMID- 18059607
TI  - Mechanisms of calcium-induced mitochondrial biogenesis and GLUT4 synthesis.
AB  - Regularly performed aerobic exercise leads to increases in skeletal muscle
      mitochondria and glucose transporter 4 (GLUT4) protein content, resulting in an
      enhanced capacity to oxidize substrates and improvements in insulin- and
      contraction-mediated glucose uptake. Although the specific mechanisms governing
      these adaptive responses have not been fully elucidated, accumulating evidence
      suggests that the increase in cytosolic Ca2+ that occurs with each wave of
      sacrolemmal depolarization is a key component of these processes. Treating L6
      muscle cells with agents that increase Ca2+ without causing reductions in ~P or
      the activation of 5'-AMP-activated protein kinase leads to increases in GLUT4 and
      mitochondrial protein contents. This effect is likely controlled through
      calcium/calmodulin-dependent protein kinase (CaMK), since KN93, a specific CaMK
      inhibitor, blocks these adaptive responses. Recent findings provide evidence that
      the activation of p38 mitogen-activated protein kinase (MAPK) is involved in the
      pathway through which Ca2+/CaMK mediates mitochondrial and GLUT4 biogenesis. p38
      MAPK initiates GLUT4 and mitochondrial biogenesis through the activation of
      transcription factors and transcriptional coactivators such as myocyte enhancer
      factor 2 (MEF2) and peroxisome proliferator-activated receptor gamma coactivator
      1 alpha (PGC-1 alpha). Subsequent increases in the content of these proteins
      further enhance Ca2+-induced GLUT4 and mitochondrial biogenesis. Since decreases
      in mitochondrial and GLUT4 contents are associated with skeletal muscle insulin
      resistance, an understanding of the mechanisms by which these processes can be
      normalized will aid in the prevention and treatment of type 2 diabetes.

PMID- 18059608
TI  - Changes in interstitial K+ and pH during exercise: implications for blood flow
      regulation.
AB  - The analysis of blood samples has clearly demonstrated that exercise is
      associated with the release of K+ and H+ from muscle. However, blood samples give
      only incomplete information about the ion changes in the muscle interstitium.
      Interstitial changes in ion composition may affect the transport properties of
      the sarcolemmal membrane, may affect fibre excitability and induce fatigue, and
      may affect sensory nerve endings. Therefore, to better understand muscle
      function, it is important to quantify the exercise-induced interstitial ion
      changes. Both interstitial K+ and H+ changes have been quantified with the
      microdialysis technique. Interstitial K+ accumulation is dependent on the
      intensity and duration of muscle activity and may reach 10 mmol/L during intense
      exercise, and the concentration in T-tubules may be even higher. Thus,
      interstitial K+ can reach a level that affects fibre excitability and the
      development of fatigue. It has also been demonstrated with microdialysis that the
      interstitial decrease in pH during muscle activity is larger than the reduction
      in blood pH. Ion changes in the interstitium may affect blood flow directly or
      indirectly. Infusion of K+ into the femoral artery in humans has demonstrated
      that blood flow is affected by changes in K+ as low as 0.1 mmol/L. The
      vasodilatory effect of K+ can be inhibited with simultaneous barium infusion,
      indicating that inward rectifier potassium (Kir)channels are involved. Acidosis
      has a direct effect on blood flow and an indirect effect, mediated by changes in
      other vasoactive compounds.

PMID- 18059609
TI  - Exercise and MEF2-HDAC interactions.
AB  - Exercise increases the metabolic capacity of skeletal muscle, which improves
      whole-body energy homeostasis and contributes to the positive health benefits of
      exercise. This is, in part, mediated by increases in the expression of a number
      of metabolic enzymes, regulated largely at the level of transcription. At a
      molecular level, many of these genes are regulated by the class II histone
      deacetylase (HDAC) family of transcriptional repressors, in particular HDAC5,
      through their interaction with myocyte enhancer factor 2 transcription factors.
      HDAC5 kinases, including 5'-AMP-activated protein kinase and protein kinase D,
      appear to regulate skeletal muscle metabolic gene transcription by inactivating
      HDAC5 and inducing HDAC5 nuclear export. These mechanisms appear to participate
      in exercise-induced gene expression and could be important for skeletal muscle
      adaptations to exercise.

PMID- 18059610
TI  - Brain neurotransmitters in fatigue and overtraining.
AB  - Since the publication of the serotonin hypothesis, numerous theories involving
      the accumulation or depletion of different substances in the brain have been
      proposed to explain central fatigue. Although the theoretical rationale for the
      "serotonin-fatigue hypothesis" is clear, several seemingly well-conducted studies
      have failed to support a significant role for 5-hydroxytryptamine in the
      development of fatigue. As brain function appears to be dependent upon the
      interaction of a number of systems, it is unlikely that a single neurotransmitter
      system is responsible for central fatigue. Several other mechanisms are involved,
      with evidence supporting a role for the brain catecholamines. Fatigue is
      therefore probably an integrated phenomenon, with complex interaction among
      central and peripheral factors. When prolonged and excessive training happens,
      concurrent with other stressors and insufficient recovery, performance decrements
      can result in chronic maladaptations that can lead to the overtraining syndrome
      (OTS). The mechanism of the OTS could be difficult to examine in detail, perhaps
      because the stress caused by excessive training load, in combination with other
      stressors, might trigger different "defence mechanisms" such as the
      immunological, neuroendocrine, and other physiological systems that all interact
      and probably therefore cannot be pinpointed as the "sole" cause of the OTS. It
      might be that, as in other syndromes, the psychoneuroimmunology (study of brain
      behavior-immune interrelationships) might shed a light on the possible mechanisms
      of the OTS, but until there is a definite diagnostic tool, it is of utmost
      importance to standardize measures that are now thought to provide a good
      inventory of the training status of the athlete. It is very important to
      emphasize the need to distinguish the OTS from overreaching and other potential
      causes of temporary underperformance such as anemia, acute infection, muscle
      damage, and insufficient carbohydrate intake.

PMID- 18059611
TI  - Protein-mediated fatty acid uptake: regulation by contraction, AMP-activated
      protein kinase, and endocrine signals.
AB  - Fatty acid transport into heart and skeletal muscle occurs largely through a
      highly regulated protein-mediated mechanism involving a number of fatty acid
      transporters. Chronically altered muscle activity (chronic muscle stimulation,
      denervation) alters fatty acid transport by altering the expression of fatty acid
      transporters and (or) their subcellular location. Chronic exposure to leptin
      downregulates while insulin upregulates fatty acid transport by altering
      concomitantly the expression of fatty acid transporters. Fatty acid transport can
      also be regulated within minutes, by muscle contraction, AMP-activated protein
      kinase activation, leptin, and insulin, through induction of the translocation of
      fatty acid translocase (FAT)/CD36 from its intracellular depot to the plasma
      membrane. In insulin-resistant muscle, a permanent relocation of FAT/CD36 to the
      sarcolemma appears to account for the excess accretion of intracellular lipids
      that interfere with insulin signaling. Recent work has also shown that FAT/ CD36,
      but not plasma membrane associated fatty acid binding protein, is involved, along
      with carnitine palmitoyltransferase, in regulating mitochondrial fatty acid
      oxidation. Finally, studies in FAT/CD36 null mice indicate that this transporter
      has a key role in regulating fatty acid metabolism in muscle.

PMID- 18059612
TI  - Skeletal muscle adaptation to fatty acid depends on coordinated actions of the
      PPARs and PGC1 alpha: implications for metabolic disease.
AB  - Dyslipidemia and intramuscular accumulation of fatty acid metabolites are
      increasingly recognized as core features of obesity and type 2 diabetes. Emerging
      evidence suggests that normal physiological adaptations to a heavy lipid load
      depend on the coordinated actions of broad transcriptional regulators such as the
      peroxisome proliferator activated receptors (PPARs) and PPAR gamma coactivator 1
      alpha (PGC1 alpha). The application of transcriptomics and targeted metabolic
      profiling tools based on mass spectrometry has led to our finding that lipid
      induced insulin resistance is a condition in which upregulation of PPAR-targeted
      genes and high rates of beta-oxidation are not supported by a commensurate
      upregulation of tricarboxylic acid (TCA) cycle activity. In contrast, exercise
      training enhances mitochondrial performance, favoring tighter coupling between
      beta-oxidation and the TCA cycle, and concomitantly restores insulin sensitivity
      in animals fed a chronic high-fat diet. The exercise-activated transcriptional
      coactivator, PGC1 alpha, plays a key role in coordinating metabolic flux through
      these 2 intersecting metabolic pathways, and its suppression by overfeeding may
      contribute to diet-induced mitochondrial dysfunction. Our emerging model predicts
      that muscle insulin resistance arises from a mitochondrial disconnect between
      beta-oxidation and TCA cycle activity. Understanding of this "disconnect" and its
      molecular basis may lead to new therapeutic approaches to combatting metabolic
      disease.

PMID- 18059614
TI  - Cortisol and GH: odd and controversial ideas.
AB  - Activation of the hypothalamo-pituitary-adrenal (HPA) axis and of the growth
      hormone/insulin-like growth factor-1 (GH/IGF-1) axis represents a physiological
      response to the energetic, metabolic, vascular, and sometimes neurophysiologic or
      psychological needs of exercise. Long-lasting increased and (or) decreased
      secretion of cortisol (the end-product of the HPA axis) or of GH is detrimental
      to health. This suggests that the activity of these hormonal axes is finely tuned
      toward homeostasia, tolerating limited prolonged homeostatic disruption. However,
      the relationships between exercise training and cortisol and GH secretion are
      full of odd and controversial ideas. In this review, the relationships between
      HPA axis adaptation to exercise training or disadaptation with overtraining will
      be discussed, with an emphasis on the limitation on the current measures used to
      profile hormonal activity. Knowledge of these relationships between cortisol and
      GH responses to exercise is an important tool to fight against doping with
      glucocorticoids and GH, and their health-damaging consequences.

PMID- 18059613
TI  - The energetic implications of uncoupling protein-3 in skeletal muscle.
AB  - Despite almost a decade of research since the identification of uncoupling
      protein-3 (UCP3), the molecular mechanisms and physiological functions of this
      mitochondrial anion carrier protein are not well understood. Because of its
      highly selective expression in skeletal muscle and the existence of mitochondrial
      proton leak in this tissue, early reports proposed that UCP3 caused a basal
      proton leak and increased thermogenesis. However, gene expression data and
      results from knockout and overexpression studies indicated that UCP3 does not
      cause basal proton leak or physiological thermogenesis. UCP3 expression is
      associated with increases in circulating fatty acids and in fatty acid oxidation
      (FAO) in muscle. Fatty acids are also well recognized as activators of the
      prototypic UCP1 in brown adipose tissue. This has led to hypotheses implicating
      UCP3 in mitochondrial fatty acid translocation. The corresponding hypothesized
      physiological roles include facilitated FAO and protection from the lipotoxic
      effects of fatty acids. Recent in vitro studies of physiological increases in
      UCP3 in muscle cells demonstrate increased FAO, and decreased reactive oxygen
      species (ROS) production. Detailed mechanistic studies indicate that ROS or lipid
      by-products of ROS can activate a UCP3-mediated proton leak, which in turn acts
      in a negative feedback loop to mitigate ROS production. Altogether, UCP3 appears
      to play roles in muscle FAO and mitigated ROS production. Future studies will
      need to elucidate the molecular mechanisms underlying increased FAO, as well as
      the physiological relevance of ROS-activated proton leak.

PMID- 18059615
TI  - Role of AMPK in skeletal muscle gene adaptation in relation to exercise.
AB  - The 5'-AMP-activated protein kinase (AMPK) functions as an intracellular fuel
      sensor that affects metabolism and gene expression. AMPK is activated in skeletal
      muscle in response to exercise and is therefore believed to be an important
      signalling molecule in regulating adaptation of skeletal muscle to exercise
      training. This review first focuses on mechanisms regulating AMPK activity during
      muscle contraction. We then discuss the role of AMPK in regulating expression of
      genes encoding various enzymes in muscle in the basal state and in relation to
      exercise training. Although decreased AMPK activity in muscle causes reduced
      protein expression of mitochondrial enzymes in the basal state, AMPK does not
      appear to be indispensable for exercise-training induced increase in
      mitochondrial enzyme expression.

PMID- 18059616
TI  - Non-obese patients with type 2 diabetes and prediabetic subjects: distinct
      phenotypes requiring special diabetes treatment and (or) prevention?
AB  - A major reason for the increased incidence of type 2 diabetes mellitus (T2DM)
      across the world is the so-called obesity epidemic, which occurs both in
      developed and developing countries. However, a large proportion of patients with
      T2DM in European and, in particular, Asian countries are non-obese. The non-obese
      T2DM phenotype is characterized by disproportionally reduced insulin secretion
      and less insulin resistance, as compared with obese patients with T2DM.
      Importantly, non-obese patients with T2DM have a similar increased risk of
      cardiovascular disease as obese T2DM patients. The risk of T2DM in non-obese
      patients is influenced by genetics as well as factors operating in utero
      indicated by low birth weight. Furthermore, this phenotype is slightly more
      prevalent among patients with latent autoimmune diabetes in adults, characterized
      by positive anti-GAD antibodies. The recently identified TCF7L2 gene polymorphism
      resulting in low insulin secretion influences the risk of T2DM in both obese and
      non-obese subjects, but is relatively more prevalent among non-obese patients
      with T2DM. Furthermore, the Pro12Ala polymorphism of the PPAR gamma gene
      influencing insulin action increases the risk of T2DM in non-obese subjects.
      Despite a "normal" body mass index, non-obese patients with T2DM are generally
      characterized by a higher degree of both abdominal and total fat masses
      (adiposity). Prevention of T2DM with lifestyle intervention is at least as
      effective in non-obese as in obese prediabetic subjects, and recent data suggest
      that metformin treatment targeting insulin resistance and non-glycemic
      cardiovascular disease risk factors is as beneficial in non-obese as in obese
      patients with T2DM. Nevertheless, non-obese patients with T2DM may progress to
      insulin treatment more rapidly as compared with obese patients with T2DM.

PMID- 18059617
TI  - Ca2+/calmodulin-based signalling in the regulation of the muscle fibre phenotype
      and its therapeutic potential via modulation of utrophin A and myostatin
      expression.
AB  - Ca2+ signalling plays an important role in excitation-contraction coupling and
      the resultant force output of skeletal muscle. It is also known to play a crucial
      role in modulating both short- and long-term muscle cellular phenotypic
      adaptations associated with these events. Ca2+ signalling via the Ca2+/calmodulin
      (CaM)-dependent phosphatase calcineurin (CnA) and via Ca2+/CaM-dependent kinases,
      such as CaMKI and CaMKII, is known to regulate hypertrophic growth in response to
      overload, to direct slow versus fast fibre gene expression, and to contribute to
      mitochondrial biogenesis. The CnA- and CaMK-dependent regulation of the
      downstream transcription factors nuclear factor of activated T cells (NFAT) and
      myocyte-specific enhancer factor 2 are known to activate muscle-specific genes
      associated with a slower, more oxidative fibre phenotype. We have also recently
      shown the expression of utrophin A, a cytoskeletal protein that accumulates at
      the neuromuscular junction and plays a role in maturation of the postsynaptic
      apparatus, to be regulated by CnA-NFAT and Ca2+/CaM signalling. This regulation
      is fibre-type specific and potentiated by interactions with the transcriptional
      regulators and coactivators GA binding protein (also known as nuclear respiratory
      factor 2) and peroxisome proliferator-activated receptor-gamma coactivator 1
      alpha. Another downstream target of CnA signalling may be myostatin, a
      transforming growth factor-beta family member that is a negative regulator of
      muscle growth. While the list of the downstream targets of CnA/NFAT- and Ca2+/CaM
      dependent signalling is emerging, the precise interaction of these pathways with
      the Ca2+-independent pathways p38 mitogen-activated protein kinase, extracellular
      signal-regulated kinases 1 and 2, phosphoinositide-3 kinase, and protein kinase B
      (Akt/PKB) must also be considered when deciphering fibre responses and plasticity
      to altered contractile load.

PMID- 18059618
TI  - Role of nuclear factor kappaB and mitogen-activated protein kinase signaling in
      exercise-induced antioxidant enzyme adaptation.
AB  - Activation of nuclear factor (NF) kappaB and mitogen-activated protein kinase
      (MAPK) pathways in skeletal muscle has been shown to enhance the gene expression
      of several enzymes that play an important role in maintaining oxidant-antioxidant
      homeostasis, such as mitochondrial superoxide dismutase (MnSOD) and inducible
      nitric oxide synthase (iNOS). While an acute bout of exercise activates NF kappaB
      and MAPK signaling and upregulates MnSOD and iNOS, administration of chemical
      agents that suppress reactive oxygen species (ROS) production can cause
      attenuation of exercise-induced MnSOD and iNOS expression. Thus, ROS generation
      during exercise may have duel effects: the infliction of oxidative stress and
      damage, and the stimulation of adaptive responses favoring long-term protection.
      This scenario explains why animals and humans involved in exercise training have
      demonstrated increased resistance to oxidative damage under a wide range of
      physiological and pathological stresses.

PMID- 18059619
TI  - Effects of physical training on endothelial function and limb blood flow in type
      2 diabetes.
AB  - The term "endothelial dysfunction" refers to the inability or attenuated effect
      of the endothelial cells in participating in the relaxation of the adjacent
      smooth muscle, thus causing less vasodilation. Although endothelial dysfunction
      is often seen in patients with type 2 diabetes, it does not necessarily follow
      that insulin resistance and (or) hyperglycemia is causing the inability to
      respond properly to vasodilatory stimuli. Rather, this could be related to the
      impact of concomitant cardiovascular risk factors that are almost invariably
      present in patients with type 2 diabetes. The impact of physical training - or
      the opposite, inactivity - on endothelial function is not fully elucidated. Some
      studies have shown positive effects of physical training, whereas others have
      not. In general, physical training can improve endothelial function when this is
      impaired. However, physical training does not seem to have any effect on
      endothelial function when this is normal.

PMID- 18059620
TI  - Effects of exercise on brain function: role of free radicals.
AB  - Reactive oxygen species (ROS) are continuously generated during aerobic
      metabolism. Certain levels of ROS, which could be dependent on the type of cell,
      cell age, history of ROS exposure, etc., could facilitate specific cell
      functions. Indeed, ROS stimulate a number of stress responses and activate gene
      expression for a wide range of proteins. It is well known that increased levels
      of ROS are involved in the aging process and the pathogenesis of a number of
      neurodegenerative diseases. Because of the enhanced sensitivity of the central
      nervous system to ROS, it is especially important to maintain the normal redox
      state in different types of neuro cells. In the last decade it became clear that
      regular exercise beneficially affects brain function as well, and can play an
      important preventive and therapeutic role in stroke and in Alzheimer's and
      Parkinson's diseases. The effects of exercise appear to be very complex and could
      include neurogenesis via neurotrophic factors, increased capillarization,
      decreased oxidative damage, and increased proteolytic degradation by proteasome
      and neprilysin. Data from our and other laboratories indicate that exercise
      induced modulation of ROS levels plays a role in the protein content and
      expression of brain-derived neurotrophic factor, tyrosine recepetor kinase B, and
      cAMP response element binding protein, resulting in better function and increased
      neurogenesis. The enhanced activities of proteasome and neprilysin result in
      decreased accumulation of carbonyls and amyloid beta-proteins, as well as
      improved memory. It appears that exercise-induced modulation of the redox state
      is an important means by which exercise benefits brain function, increases the
      resistance against oxidative stress, and facilitates recovery from oxidative
      stress.

PMID- 18059621
TI  - Hormetic effects of regular exercise in aging: correlation with oxidative stress.
AB  - To explore mechanisms of the beneficial consequences of regular exercise, we
      studied the effects of regular swimming and treadmill exercise on oxidative
      stress in the brain and liver of rats. Protein carbonyl was significantly reduced
      and the activity of proteasome was upregulated in the brain extracts of young and
      middle-aged animals after 9 weeks of swimming training. Furthermore, their
      cognitive functions were significantly improved. In separate experiments, the
      activation of transcription nuclear factor kappaB was attenuated in the liver of
      old rats after 8 weeks of regular treadmill exercise and the DNA binding activity
      of glucocorticoid receptor reduced with age was restored, suggesting that
      inflammatory reactions are alleviated by the regimen. This was accompanied by
      upregulation of the glutathione level and reduced reactive oxygen species
      generation. Similar training reduced the 8-oxodeoxyguanosine content in the
      nuclear and mitochondrial DNA of the liver of old rats. Thus, these findings,
      together with reports of other investigators, suggest that moderate regular
      exercise attenuates oxidative stress. The mild oxidative stress possibly elicited
      by regular exercise appears to manifest a hormesis-like effect in nonmuscular
      tissues, constituting beneficial mechanisms of exercise by adaptively
      upregulating various antioxidant mechanisms, including antioxidative and repair
      degradation enzymes for damaged molecules. Importantly, the adaptation induced by
      regular exercise was effective even if initiated late in life.

PMID- 18059622
TI  - Molecular mechanisms of life- and health-span extension: role of calorie
      restriction and exercise intervention.
AB  - The aging process results in a gradual and progressive structural deterioration
      of biomolecular and cellular compartments and is associated with many
      pathological conditions, including cardiovascular disease, stroke, Alzheimer's
      disease, osteoporosis, sarcopenia, and liver dysfunction. Concomitantly, each of
      these conditions is associated with progressive functional decline, loss of
      independence, and ultimately disability. Because disabled individuals require
      care in outpatient or home care settings, and in light of the social, emotional,
      and fiscal burden associated with caring for an ever-increasing elderly
      population, research in geriatric medicine has recently focused on the biological
      mechanisms that are involved in the progression towards functional decline and
      disability to better design treatment and intervention strategies. Although not
      completely understood, the mechanisms underlying the aging process may partly
      involve inflammatory processes, oxidative damage, mitochondrial dysfunction, and
      apoptotic tissue degeneration. These hypotheses are based on epidemiological
      evidence and data from animal models of aging, as well as interventional studies.
      Findings from these studies have identified possible strategies to decrease the
      incidence of age-related diseases and delay the aging process. For example,
      lifelong exercise is known to extend mean life-span, whereas calorie restriction
      (CR) increases both mean and maximum life-span in a variety of species. Optimal
      application of these intervention strategies in the elderly may positively affect
      health-related outcomes and possibly longevity. Therefore, the scope of this
      article is to (i) provide an interpretation of various theories of aging from a
      "health-span" perspective; (ii) describe interventional testing in animals (CR
      and exercise); and (iii) provide a translational interpretation of these data.

PMID- 18059623
TI  - Gene regulation by mechanotransduction in fibroblasts.
AB  - Mechanical forces are important for connective tissue homeostasis. How do
      fibroblasts sense mechanical stress and how do they translate this information
      into an adaptive remodeling of the extracellular matrix (ECM)? Tenascin-C is
      rapidly induced in vivo by loading muscles and in vitro by stretching
      fibroblasts. Regulation of tenascin-C expression by mechanical signals occurs at
      the transcriptional level. Integrin receptors physically link the ECM to the
      cytoskeleton and act as force transducers: intracellular signals are triggered
      when integrins engage with ECM, and later when forces are applied. We found that
      cyclic strain does not induce tenascin-C messenger ribonucleic acid (mRNA) in
      fibroblasts lacking the beta1-integrin chain. An important link in integrin
      dependent mechanotransduction is the small guanosine 5'-triphosphatase. RhoA and
      its target kinase, ROCK. In fibroblasts, cyclic strain activates RhoA and thereby
      induces ROCK-dependent actin assembly. Interestingly, tenascin-C mRNA induction
      by cyclic strain was suppressed by relaxing the cytoskeleton with a ROCK
      inhibitor or by actin depolymerization. Conversely, chemical activators of RhoA
      enhanced the effect of strain both on actin dynamics and on tenascin-C
      expression. Thus, RhoA/ROCK-controlled actin dynamics are required for the
      induction of specific ECM genes by mechanical stress. These findings have
      implications for the understanding of regeneration and for tissue engineering.

PMID- 18059624
TI  - Regulation of Na+-K+ homeostasis and excitability in contracting muscles:
      implications for fatigue.
AB  - The performance of skeletal muscles depends on their ability to initiate and
      propagate action potentials along their outer membranes in response to motor
      signals from the central nervous system. This excitability of muscle fibres is
      related to the function of Na+ and K+ and Cl- channels and to steep chemical
      gradients for the ions across the cell membranes, i.e., the sarcolemma and T
      tubular membranes. At rest, the chemical gradients for Na+ and K+ are maintained
      within close limits by the action of the Na+-K+ pump. During contractile
      activity, however, the muscles lose K+, which causes an increase in the
      concentration of K+ in the extracellular compartments of the body, the magnitude
      of which depends on the intensity of the exercise and the size of the muscle
      groups involved. Since the ensuing reduction in the chemical K+ gradient can have
      adverse effects on muscle excitability, it has repeatedly been suggested that,
      during intense exercise, the loss of K+ from muscle fibres can contribute to the
      complex set of mechanisms that leads to the development of muscle fatigue. In
      this review, aspects of the regulation of Na+-K+ homeostasis and excitability in
      contracting muscles is discussed within this context, together with the
      implications for the contractile function of skeletal muscles.

PMID- 18059626
TI  - Mapping the epitopes of antibodies.

PMID- 18059627
TI  - Cellulose-bound peptide arrays: preparation and applications.

PMID- 18059628
TI  - The SIGEX scheme: high throughput screening of environmental metagenomes for the
      isolation of novel catabolic genes.

PMID- 18059629
TI  - Dynamic light scattering as a relative tool for assessing the molecular integrity
      and stability of monoclonal antibodies.

PMID- 18059630
TI  - Protein ligation: applications in NMR studies of proteins.

PMID- 18059631
TI  - Mass spectrometry-based quantitative proteomics.

PMID- 18059632
TI  - Expanding adeno-associated viral vector capacity: a tale of two vectors.

PMID- 18059633
TI  - Modulation of immunoglobulin gene conversion in chicken DT40 by enhancing histone
      acetylation, and its application to antibody engineering.

PMID- 18059634
TI  - Using homologous recombination to manipulate the genome of human somatic cells.

PMID- 18059635
TI  - Practical applications of bacterial functional genomics.

PMID- 18059636
TI  - Engineering human embryonic stem cell differentiation.

PMID- 18059637
TI  - Production of polyunsaturated fatty acids in transgenic plants.

PMID- 18059638
TI  - Current cell-based approaches for the treatment of diabetes mellitus.

PMID- 18059640
TI  - RNA as a versatile and powerful platform for engineering genetic regulatory
      tools.

PMID- 18059641
TI  - Advances in animal disease surveillance and biosecurity.

PMID- 18059639
TI  - Genetic modification of human embryonic stem cells.

PMID- 18059642
TI  - Advances in biosecurity to 2010 and beyond: towards integrated detection,
      analysis and response to exotic pest invasions.
AB  - In order to limit the number and impact of exotic pest invasions, leading-edge
      technologies must be embraced and embedded within integrated national and
      international biosecurity systems. Outlined here are recent advances in the
      detection of exotic pests, and prospects for the early recognition of disease.
      Applications of new tools are described, using our understanding of the genomes
      of pathogens and vectors. In addition, the role of mathematical and simulation
      models to aid both biosecurity planning, and decision making in the face of an
      epidemic, are discussed, and recent attempts to unify epidemiology and
      evolutionary dynamics are outlined. Given the importance of emerging diseases and
      zoonoses, the need to align human and veterinary surveillance within fully
      integrated systems is underlined.

PMID- 18059643
TI  - Decision support systems for monitoring and maintaining health in food animal
      populations.
AB  - To mitigate the effects of risks to food safety and infectious disease outbreaks
      in farmed animals, animal health authorities need to have systems in place to
      identify and trace the source of identified problems in a timely manner. In the
      event of emergencies, these systems will allow infected or contaminated premises
      (and/or animals) to be identified and contained, and will allow the extent of
      problems to be communicated to consumers and trading partners in a clear and
      unambiguous manner. The key to achieving these goals is the presence of an
      effective animal health decision support system that will provide the facilities
      to record and store detailed information about cases and the population at risk,
      allowing information to be reported back to decision makers when it is required.
      Described here are the components of an animal health decision support system,
      and the ways these components can be used to enhance food safety, responses to
      infectious disease incursions, and animal health and productivity. Examples are
      provided to illustrate the benefit these systems can return, using data derived
      from countries that have such systems (or parts of systems) in place. Emphasis is
      placed on the features that make particular system components effective, and
      strategies to ensure that these are kept up to date.

PMID- 18059644
TI  - Simulation modelling as a tool for evaluating surveillance programmes for
      detection of the Asian honeybee mite ( Varroa destructor ) in the South Island of
      New Zealand.
AB  - AIM: To use a simulation model of the spread of the Asian honeybee mite (Varroa
      destructor) amongst apiaries, to evaluate a series of detection surveillance
      programmes for the South Island of New Zealand. METHODS: Five potential incursion
      sites into the South Island were selected. A stochastic spatial simulation model,
      Varroa_ sim, was adapted to simulate spread of the mite from these sites as a
      series of silent-phase propagating epidemics. The study population comprised all
      apiaries in the South Island registered in the Ministry of Agriculture and
      Forestry's (MAF's) apiary database in 2003. Six different surveillance programmes
      were simulated to try and detect the mite. Three of these were the actual multi
      stage sampling plans conducted during the autumn (March-May) of 2001, 2002 and
      2003, and the other three involved simple random sampling with sampling fractions
      equivalent to the actual numbers of apiaries tested in each of those years. The
      relative performances of the different surveillance plans were evaluated in terms
      of their ability to detect the mite early before it had spread too far and whilst
      there might still be a chance of eradication. RESULTS: There were 13,798
      registered apiaries in the South Island with valid map coordinates in the apiary
      database at the time of the study. The model generated 50 epidemics against which
      the various surveillance programmes were evaluated. The actual surveillance
      programmes conducted during the autumn of 2001 and 2002 generally performed
      fairly well in detecting the mite. The programme conducted in autumn 2003
      detected the mite reasonably well in high-risk areas, but was very poor in low
      risk areas. The simple random sampling strategies performed surprisingly well,
      and their relative rankings were proportional to the sampling fractions employed.
      CONCLUSIONS: This study showed the value in using a spatial simulation model to
      generate plausible silent-phase epidemics, against which detection surveillance
      programmes could be evaluated, in ways that would otherwise not be possible.

PMID- 18059646
TI  - Application of modelling to determine the absence of foot-and-mouth disease in
      the face of a suspected incursion.
AB  - AIM: To use disease modelling to inform a response team about the number of
      animals per herd/flock to be examined, and the start date and duration of
      clinical surveillance required to be confident that foot-and-mouth disease (FMD)
      was not present on an island in New Zealand with a population of approximately
      1,600 cattle, 10,000 sheep and a small number of pigs, goats and alpacas.
      METHODS: Because the probability of detecting clinical disease in (the) primary
      case(s) in larger herds and flocks was extremely low, deterministic and
      stochastic mathematical SLIR (susceptible, latent, infectious, recovered) models
      for the transmission of infection were constructed to estimate the date when
      clinical lesions in herds and flocks would be detected with 95% confidence.
      Surveillance targeted the first wave of infections following a suspect index
      case. RESULTS: If 70 cattle in herds of about 400 cattle were examined it was
      estimated it would take approximately 13 (90% stochastic range 9-19) days from
      first exposure before it would be possible to achieve 95% confidence for
      detecting clinical signs for a low-virulence virus, and 9 (7-14) days for a high
      virulence virus. The duration of sufficiently accurate clinical detection was 17
      (15-19) days and 13 (12-14) days for low- and high-virulence viruses,
      respectively. A sample of 70 sheep from flocks of >1,000 would be required to
      achieve clinical detection at about the same time but with a shorter period of
      detection than for cattle. The duration of effective detection could be increased
      by examining a larger sample in most sheep flocks, however the small size of many
      cattle herds in the study population limited the confidence of detecting group
      level disease in cattle, therefore necessitating repeated herd inspections. The
      model suggested that group-level detection was not feasible if it was based on
      elevated body temperature alone because of short durations of fever in infected
      animals. CONCLUSION AND CLINICAL RELEVANCE: Simulation modelling is a useful and
      powerful tool for informing ongoing surveillance activities in the face of an
      exotic disease incursion. Results of modelling suggested to start clinical
      inspection activities at 4 days and to continue regular inspection twice a week
      for about 35 days after the date of first exposure, to satisfy the required 95%
      confidence threshold of clinical detection of FMD in cattle herds and sheep
      flocks.

PMID- 18059645
TI  - A comparison of predictions made by three simulation models of foot-and-mouth
      disease.
AB  - AIMS: To describe results of a relative validation exercise using the three
      simulation models of foot-and-mouth disease (FMD) in use by the quadrilateral
      countries (QUADS; Australia, Canada, New Zealand, and United States of America;
      USA). METHODS: A hypothetical population of farms was constructed and, following
      the introduction of an FMD-like disease into a single farm, spread of disease was
      simulated using each of the three FMD simulation models used by the QUADS
      countries. A series of 11 scenarios was developed to systematically evaluate the
      key processes of disease transmission and control used by each of the three
      models. The predicted number of infected units and the size of predicted outbreak
      areas for each scenario and each model were compared using the Kruskal-Wallis
      test. Agreement among the three models in terms of geographical areas predicted
      to become infected were quantified using Fleiss' Kappa statistic. RESULTS:
      Although there were statistically significant differences in model outputs in
      terms of the numbers of units predicted to become infected, the temporal onset of
      infection throughout the simulation period, and the spatial distribution of
      infected units, these differences were generally small and would have resulted in
      the same (or similar) management decisions being adopted in each case.
      CONCLUSIONS: Agreement among the three models in terms of the numbers of premises
      predicted to become infected, the temporal onset of infection throughout the
      simulation period, and the spatial distribution of infected premises provides
      evidence that each of the model developers are consistent in their approach to
      simulating the spread of disease throughout a population of susceptible
      individuals. This consistency implies that the assumptions taken by each
      development team are appropriate, which in turn serves to increase end-user
      confidence in model predictions. CLINICAL RELEVANCE: Relative validation is one
      of a number of steps that can be undertaken to increase end-user confidence in
      predictions made by infectious disease models.

PMID- 18059647
TI  - Severity and distribution of ventral thoracolumbar spondylosis and histological
      assessment of associated intervertebral disc degeneration in cull rams.
AB  - AIM: To conduct a pilot study investigating the incidence and pathology of
      spondylosis in a sample of cull rams in New Zealand. METHODS: Vertebral columns
      from 51 cull rams from different properties were assessed radiographically for
      evidence of spondylosis. They were graded according to severity, using a four
      point grading system. Samples of intervertebral discs representing different
      grades of spondylosis were examined histopathologically. RESULTS: Forty (78%)
      rams had spondylosis in at least one intervertebral space. Of these, 11 had
      ankylosis involving one or more intervertebral spaces. The frequency of
      spondylosis was greater in the thoracic than lumbar region (p<0.001), and was
      most frequent between T10-T11. Histopathological examination of intervertebral
      discs associated with all grades of spondylosis revealed degenerative changes in
      the annulus fibrosis. CONCLUSIONS: Spondylosis appeared to be common in cull rams
      and affected thoracic and lumbar vertebrae. It often involved ankylosis of
      adjacent vertebrae, and was associated with degeneration of the intervertebral
      disc. CLINICAL RELEVANCE: Spondylosis may reduce the serving ability of rams and
      be an important underlying reason for culling. The pathogenesis of spondylosis is
      unknown but may involve high mating frequencies during the breeding season.

PMID- 18059648
TI  - A cross-sectional survey of Thoroughbred stud farm management in the North Island
      of New Zealand.
AB  - AIM: To obtain initial baseline data on the management of Thoroughbred stud farms
      in the North Island of New Zealand. METHODS: Data on the management of
      Thoroughbred stud farms were collected from a sample of 22 stud farms located in
      the south Auckland/Waikato region (n=15) and lower North Island (n=7) of New
      Zealand, using a face-to-face survey. The studmaster provided information on the
      size, scope and management of the farms during the 2004/2005 breeding season.
      Analysis was based on the location of the farm and size of the breeding operation
      (number of resident mares). RESULTS: Effective farm size ranged from 20 to 526 ha
      and averaged 167 (standard error (SE) 36) and 88 (SE 49) ha in the south
      Auckland/Waikato and lower North Island areas, respectively. Some farms in the
      Auckland/Waikato region stood shuttle stallions. The median number of stallions
      per farm was three (range 0-9), and the median mare-to-stallion ratio was 43
      (range 10-250). The farms had a mean of 50 (range 7-180) wet mares and 21 (range
      0-100) dry mares. The number of mares per breeding stallion increased with
      increasing size of breeding operation (p=0.04), being 28 (95% confidence interval
      (CI) = 10-56) vs 40 (95% CI=16-74) vs 74 (95% CI=44-113) for moderate (<or=70
      mares), medium (90-199 mares) and large (>or=200 mares in total) operations,
      respectively. Seventy-one percent of farms aimed to breed dry mares early in the
      breeding season, and used a combination of lights, hormone therapy, and rising
      plane of nutrition to achieve this. Foaling took place in foaling paddocks
      monitored using a night foaling attendant (17/22) or with foaling alarms (5/22).
      At birth, 17/22 studmasters routinely administered antibiotics, 14/22
      administered tetanus antitoxin, 9/22 administered an enema to foals, and 2/22 did
      not routinely administer prophylactic treatments. Weaning occurred at 5 (range
      3.7-7) months of age, and foals were confined to a box for 1-2 weeks on 16/22
      farms. Weaned foals were drenched with anthelmintics every 7 (range 4-9) weeks,
      and were fed 2.9 (range 1-6) kg of concentrate feed while at pasture until
      intensive management associated with preparation of the horses for auction began
      13 (range 6-20) weeks before the yearling sales. Eight farms weighed the
      weanlings, at least monthly, to monitor growth. CONCLUSIONS AND CLINICAL
      RELEVANCE: The management of Thoroughbred horses was relatively consistent
      throughout the regions surveyed. Utilisation of breeding stallions tended to be
      more efficient on the larger stud farms in the south Auckland/Waikato region.
      Even though foals are grown at pasture they are often provided with large
      quantities of concentrate feed.

PMID- 18059649
TI  - Intra-uterine transmission of Mycobacterium avium subsp paratuberculosis in
      subclinically affected red deer (Cervus elaphus).
AB  - AIM: To determine the rate of transmission of Mycobacterium avium subsp
      paratuberculosis (M. ptb) from hind to fetus in utero, and the risk of
      transmission from dam to fawn via infected colostrum and milk in subclinically
      affected red deer hinds. METHODS: Hinds were sourced from farms in Otago or
      Southland and selected for the study if they were positive to the immunoglobulin
      G1 (IgG1) modified enzyme-linked immunosorbent assay (ELISA) (Paralisa) and
      exhibited no clinical signs of Johne's disease. The hinds (n=35) were sent to a
      deer slaughter premises (DSP; n=31) or were killed on-farm (n=4). All post-mortem
      samples were collected from the fetus first and then from the dam, taking care to
      avoid cross contamination between samples. Fresh samples (n=185) were collected
      for culture, and tissue samples (n=72) were collected from 24 hinds and their
      fetuses for histopathological examination. RESULTS: A total of 24/35 hinds
      selected were suitable for inclusion in the study. Eighteen of these pregnant
      hinds were culture-positive for M. ptb, and 14 of these had culture-positive
      fetuses, representing a transmission rate of 78% (95% confidence interval (CI)
      =0.58-0.98) from dam to fetus. Of the 16 mammary glands sampled, 11 (69%) were
      culture-positive for M. ptb while 12/15 (80%) mammary lymph nodes sampled were
      also culture-positive. CONCLUSIONS: This study demonstrated a high rate of
      transmission of M. ptb from dam to fetus in red deer, and a potential risk of
      transmission to fawns suckling from mothers that are subclinically affected with
      Johne's disease.

PMID- 18059650
TI  - A practical approach to managing the risks of iodine deficiency in flocks using
      thyroid - weight: birthweight ratios of lambs.
AB  - AIM: To establish a protocol for determining the iodine status of a flock and
      managing the risks of iodine deficiency, using thyroid-weight:birthweight ratios
      of newborn lambs and serum iodine concentrations of ewes. METHODS: Data were
      collected from iodine supplementation studies in Southland and Rangitikei, of
      sheep fed exclusively pasture or pasture plus brassica during the latter half of
      gestation (n=350, or 89 per treatment group). The ewes were supplemented pre
      mating or at the time of pregnancy scanning with an injection of long-acting
      iodised oil. Serum iodine concentrations were measured in ewes prepartum in
      Rangitikei and postpartum at both locations. The thyroid-weight:birthweight
      ratios (as g/ kg) in 229 newborn lambs were determined at post-mortem examination
      and compared between iodine supplemented vs unsupplemented flocks using probit
      analysis. Samples of pasture and kale were analysed monthly for determination of
      iodine and selenium. RESULTS: Initial mean serum iodine concentration of all ewes
      was 41 mug iodine/L. Supplementation increased serum iodine concentrations
      regardless of forage fed, and concentrations remained high for between 127 and
      206 days. The range of thyroid-weight:birthweight ratios in lambs from
      supplemented ewes was 0.09-0.70 (mean 0.35, standard deviation (SD) 0.147) g/kg.
      Among lambs from unsupplemented ewes, the range was much wider (0.21-8.5; mean
      1.61, SD 1.95 g/kg). About half of those ratios were >0.8 g/kg and clearly
      indicative of goitre, including 62% from the groups on brassica and 18% from the
      Rangitikei group fed exclusively pasture. Probit calculations showed that a ratio
      of 0.40 (95% confidence interval (CI)=0.29-0.47) g/kg predicted with 35%
      probability, and a ratio of 0.80 (95% CI=0.70-0.99) g/kg predicted with 90%
      probability that a lamb came from an unsupplemented flock. CONCLUSIONS: Compared
      to iodine concentrations in forages, thyroid-weight:birthweight ratios more
      accurately reflected the iodine status of the flock and could be used to identify
      which flocks to supplement the following year. Serum iodine concentrations of
      ewes measured before or after lambing did not reflect forage fed, but values near
      40 mug/L were associated with goitrous lambs. CLINICAL RELEVANCE: Thyroid
      weight:birthweight ratios >0.8 g/kg were indicative of iodine deficiency, and
      ewes should be supplemented pre-mating or during pregnancy to prevent goitre the
      following year. Ratios <0.4 g/kg rarely occurred among deficient flocks, so the
      probability of benefit from supplementation was low. Intermediate ratios were
      ambiguous, and the iodine status of the flock could not be determined from
      biomarkers. In such cases individual-farm supplementation trials might be
      required to detect and manage the risks of marginal deficiency.

PMID- 18059651
TI  - Growth curves from birth to weaning for Thoroughbred foals raised on pasture.
AB  - AIM: To mathematically describe the growth of a population of Thoroughbred foals
      reared on pasture in New Zealand from birth to weaning. METHODS: Twice-monthly
      liveweight data (including birthweight; BW) from 218 foals (98 colts and 120
      fillies) born over a 6-year period, and reared on four different pasture types,
      were available for analysis. Data truncated to the time of weaning (107-217 days
      old) provided 3,200 data points. After testing for non-linearity of the
      relationship of age and liveweight (LW), five non-linear regression equations
      were tested for goodness of fit. RESULTS: Colts and fillies had similar BW,
      weaning ages, weaning weights (WW) and average daily gain (ADG) between birth and
      weaning (ADG b-w). Weaning age explained 48% (p<0.001) of the variation in WW and
      11% (p<0.001) of the variation in ADGb-w. After correction for weaning age, BW
      explained 16% (p<0.001) of the variation in WW and 6% (p<0.001) of the variation
      in ADG b-w. The best fit of age and LW was the polynomial equations based on
      Akaike's information criteria (AIC), residual variance (RV), residual standard
      deviation (RSD), and coefficient of determination (R2). The most accurate,
      biologically sound representation of growth was provided by Brody's type
      equation: LW = [b0- (b0-BW) x e(-b1 x age)], and an equation including BW: LW =
      [((b0 x BW x age) + BWb1)b2], that was developed in this study (b0 is an
      intercept, b1 and b2 are regression coefficients, and e is the base of natural
      logarithms). The advantage of the Brody's equation is that ADG at a given LW can
      simply be calculated as: ADG (kg/day) = (b0 x b1)-b1 x LW. CONCLUSIONS AND
      CLINICAL RELEVANCE: The similarity of the present data with growth data from the
      Northern Hemisphere provides further recognition that foals reared on pasture can
      grow as well as foals reared in grain-based systems in the Northern Hemisphere.
      BW provides a logical set point for the explanation of growth of the foal up to
      weaning, rather than the use of polynomial equations, which do not fully describe
      the biology of growth, even though they provide an accurate mathematical
      description.

PMID- 18059652
TI  - Analysis of the risk of introduction and spread of porcine reproductive and
      respiratory syndrome virus through importation of raw pigmeat into New Zealand.
AB  - AIMS: To determine the frequency with which porcine reproductive and respiratory
      syndrome (PRRS) virus (PRRSv) would become established in a non-commercial pig
      herd in New Zealand due to illegal feeding of uncooked food waste containing
      virus-contaminated pigmeat. To determine the likelihood of a single incursion
      resulting in a multi-farm outbreak of the disease, and describe the spatio
      temporal characteristics of such an outbreak. METHODS: A Monte Carlo simulation
      model was constructed to determine the expected annual frequency of PRRSv
      infection being initiated in a non-commercial pig herd as a result of inadvertent
      feeding of pigmeat imported from countries endemically infected with the disease.
      Once the likelihood of PRRSv becoming established in a single pig herd was
      determined, stochastic spatially explicit infectious disease modelling software
      was utilised to model the temporal and spatial characteristics of the resulting
      epidemic. RESULTS: Assuming the proportion of imported pigmeat remained at
      current levels, consumption patterns of pigmeat in households in New Zealand
      remained steady, and limited compliance with recently reintroduced regulations to
      prevent feeding of uncooked food waste, at least 4.3 pig herds per year were
      predicted to become infected with PRRSv. Simulation modelling of PRRSv epidemics
      related to initial infection of a non-commercial farm produced an estimate that
      36% of these incursions would spread from the initial herd, and that these
      outbreaks would involve 93 herds on average in the first year. By increasing the
      estimated persistence of PRRSv infection in small herds, an average of 205 herds
      became infected in the first year. CONCLUSIONS: Given a mean of 4.3 infected
      premises per year and a 36% probability of infection spreading beyond the initial
      infected herd, there was a 95% likelihood of a multi-farm PRRS outbreak occurring
      within 3 years. CLINICAL RELEVANCE: Introduction of PRRSv through importation of
      virus-contaminated pigmeat presents a high risk for establishment of the disease
      in the pig industry in New Zealand.

PMID- 18059653
TI  - A survey of feeding , management and faecal pH of Thoroughbred racehorses in the
      North Island of New Zealand.
AB  - AIM: To identify feeding and management variables associated with variation in
      faecal pH within a population of intensively managed Thoroughbred racehorses in
      New Zealand. METHODS: A cross-sectional survey was conducted of 16 racehorse
      trainers in the North Island of New Zealand. Interviews were conducted at the
      trainers' stables to obtain information on feeding and management of horses, and
      faecal samples were collected and faecal pH measured. RESULTS: Ninety-seven
      percent of the horses surveyed were confined in an area <or=5 x 5 m for >or=12
      h/day. Trainer's age, number of years they had trained horses, age and gender of
      horses, weeks in race training, racing class, frequency of feeding, bedding type,
      and exercise workload had no effect on mean faecal pH. Acidic faecal pH (pH
      <or=6.32) was associated with stables with <or=12 horses, and trainers at stables
      with <or=12 horses offered more concentrate feed than those at stables with >12
      horses. Acidic faecal pH was associated with trainers who offered 4 kg of grain
      as the only form of concentrate fed, or offered <or=2.25 kg hay/day. Horses that
      displayed stable vices had less acidic faecal pH than horses that did not display
      stable vices, viz pH 6.70 (standard error of the mean (SEM) 0.135) vs 6.43 (SEM
      0.029) (p=0.04). CONCLUSIONS AND CLINICAL RELEVANCE: Racehorse management in New
      Zealand is similar to that observed in other major racing countries. Trainers
      with <or=12 horses fed more concentrates and their horses had lower faecal pH
      than those of trainers with >12 horses. Irrespective of management system, it
      appears important to provide at least 2.25 kg of hay/day ad libitum, to buffer
      hindgut acidosis associated with diets high in soluble carbohydrate.

PMID- 18059654
TI  - Effect of the ratio of teaser rams used prior to breeding on the reproductive
      performance of ewe hoggets.
AB  - AIM: To determine the effects of the ratio of vasectomised (teaser) rams to ewe
      hoggets used prior to breeding on the breeding performance and pregnancy rate of
      ewe hoggets. METHODS: Romney-composite ewe hoggets (n=1,180), 7-8 months of age,
      were randomly assigned to one of five treatment groups (Day 1) and either exposed
      to harnessed teaser rams at a teaser-ram:ewe-hogget ratio of 1:32 (n=193
      hoggets), 1:66 (n=199), 1:98 (n=197), or 1:197 (n=395), for 17 days prior to the
      breeding period, or not exposed to teasers (unteased; n=196). Harnessed entire
      rams were then introduced for the duration of two oestrous cycles (34 days).
      Using crayon marks, ewe hoggets were identified as having been mated during the
      first 17 days only, during the second 17 days only, during both 17-day periods,
      or not mated. Hoggets were weighed on Days 1 and 18. All ewe hoggets were scanned
      for pregnancy using ultrasound, 57 days after the end of the breeding period.
      RESULTS: Hogget groups did not differ in liveweight at Day 1, but at Day 18
      hoggets exposed to teasers at a ratio of 1:66 were lighter, and those exposed to
      teasers at a ratio of 1:32 were heavier than all other groups by up 3.0 kg
      (p<0.05). Unteased ewe hoggets were less likely to be pregnant to the first 17
      days of breeding compared with all teased groups, by at least 16.4% (p<0.05).
      Over the entire 34-day breeding period, however, only those teased at a ratio of
      1:32 were more likely to be pregnant, by 11.9%, than unteased hoggets (p<0.05).
      Within the teased hogget groups, there were no differences between groups for
      either the percentage mated in the first 17 days of breeding only, or those
      pregnant to either the first 17 days of breeding only or the entire breeding
      period. CONCLUSIONS: The results of this study indicate that teaser-ram:ewe
      hogget ratios as high as 1:197 can increase the percentage of ewe hoggets bred in
      the first 17 days of mating by at least 16.4%. Across the range of ratios used
      there was little difference in breeding pattern or pregnancy rate, although
      results might suggest ratios <or=1:32 are more effective compared with those
      >1:98.

PMID- 18059655
TI  - Descriptive summary of an outbreak of porcine post-weaning multisystemic wasting
      syndrome (PMWS ) in New Zealand.
AB  - CASE HISTORY: Investigations were conducted to determine the cause of an acute,
      multi-farm outbreak of porcine respiratory disease that included diarrhoea and
      subsequent loss of body condition in affected pigs. A definition for post-weaning
      multisystemic wasting syndrome (PMWS) including both clinical and pathological
      features, previously developed for the pig industry in New Zealand, was applied
      to the current outbreak. In addition to self-reporting by owners of affected
      farms, local veterinarians, disease and epidemiology consultants, and animal
      health officials from the Ministry of Agriculture and Forestry (MAF) were
      involved in conducting farm visits and submission of diagnostic specimens.
      CLINICAL FINDINGS AND DIAGNOSIS: Pathogens known to be endemic in the pig
      industry in New Zealand as well as likely exotic diseases were excluded as
      causative agents of the outbreak. Clinical signs including dyspnoea, diarrhoea,
      and rapid loss of body condition were consistent with the New Zealand case
      definition for PMWS. Interstitial pneumonia, pulmonary oedema, generalised lymph
      node enlargement, and presence of porcine circovirus type 2 (PCV2) inclusion
      bodies were consistently identified in affected pigs. Classical swine fever virus
      (CSFv), Porcine reproductive and respiratory syndrome virus (PRRSv), and
      Influenza virus were ruled out, using molecular and traditional virological
      techniques. Spread of the disease between farms was hypothesised to be
      facilitated by locally migrating flocks of black-backed seagulls. The original
      source of the disease incursion was not identified. DIAGNOSIS: Based on the
      consistent presence of circovirus-associated lesions in lymphoid tissues in
      combination with generalised enlargement of lymph nodes, histiocytic interstitial
      pneumonia, clinical wasting, and poor response to antibiotic therapy, a diagnosis
      of PMWS was made. CLINICAL RELEVANCE: PMWS should be considered in the
      differential diagnoses of sudden onset of respiratory dyspnoea, diarrhoea, and
      rapid loss of body condition in young pigs in New Zealand pig herds.

PMID- 18059656
TI  - Failure of zinc supplementation to prevent severe facial eczema in cattle fed
      excess copper.
AB  - CASE HISTORY: A 400-cow dairy unit in the Waikato suffered a severe outbreak of
      facial eczema (FE) despite consistent zinc supplementation and significantly
      elevated serum zinc concentrations. CLINICAL FINDINGS: FE prevention had begun in
      mid-January 2006, via zinc sulphate supplementation in the water.
      Photosensitisation was reported on 06 April, contemporaneous with a marked
      increase in the number of Pithomyces chartarum spores in pasture samples. Within
      10 days of this first clinical case, 100 affected cows had been dried off, eight
      of which subsequently died or were culled. Blood samples were collected from ten
      affected cows; all had serum zinc concentrations >17 micromol/L, and eight had
      gamma-glutamyl transferase (GGT) activities >200 U/ml, indicating that the
      photosensitisation was secondary to liver damage, i.e. probably FE. Further
      investigation identified that this herd had been receiving excess copper
      supplementation; 4/6 culled cows had liver copper concentrations within or above
      the marginal range for copper toxicity. DIAGNOSIS: Severe FE despite zinc
      supplementation that increased serum zinc concentrations above recommended
      levels. CLINICAL RELEVANCE: As zinc supplementation significantly reduces
      apparent copper status, copper supplementation is often used to counteract this.
      Previous excess copper intake may reduce the efficacy of zinc in preventing FE,
      thus copper intake should be assessed prior to the start of zinc supplementation.

PMID- 18059657
TI  - Abortions in sheep caused by Salmonella Brandenburg: pathological findings.

PMID- 18059658
TI  - Feline immunodeficiency virus subtypes in domestic cats in New Zealand.

PMID- 18059660
TI  - Wavelength-division-multiplexing optical packet switch with heterogeneous
      wavelength conversion capabilities.
AB  - Among the wavelength-division-multiplexing (WDM) optical packet switches (OPSs)
      using wavelength converters (WCs), a shared-per-node switch architecture has been
      considered as a way to utilize WCs efficiently. We propose a new switch control
      algorithm for the architecture. The proposed algorithm, different from previous
      algorithms, focuses on using the heterogeneous WC blocks (HeWCBs), where a HeWCB
      consists of WCs with different wavelength conversion degrees (WCDs). The results
      show that the WDM OPS architecture using HeWCBs reduces the number of WCs with a
      higher WCD, while minimizing the packet loss from wavelength contention at
      outbound links.

PMID- 18059662
TI  - Rapid characterization of the ultraviolet induced fiber Bragg grating complex
      coupling coefficient as a function of irradiance and exposure time.
AB  - We report the application of optical frequency domain reflectometry and a
      discrete-layer-peeling inverse scattering algorithm to the spatial
      characterization of the UV induced complex coupling coefficient during fiber
      Bragg grating growth. The fiber grating is rapidly characterized using this
      technique to give irradiance dependent growth as a function of exposure time,
      thereby providing the complete characterization of the coupling coefficient in
      the form of a "growth surface," which is related to the fiber's photosensitivity.
      We compare measurements of fiber Bragg grating growth in SMF-28 when exposed to
      continuous wave 244 nm irradiation from 0 to 90 W cm(-2) for exposure times up to
      3230 s with a selection of other fibers including high germanium concentration
      fiber and erbium doped fiber.

PMID- 18059661
TI  - Multispectral diffuse optical tomography with absorption and scattering spectral
      constraints.
AB  - We present a new method to simultaneously reconstruct the images of
      oxyhemoglobin, deoxyhemoglobin, and water concentrations, as well as the volume
      fraction images of the scattering particles using continuous wave multispectral
      diffuse optical tomography with the absorption and scattering spectral prior
      constraints. In this method, the nonlinear relationship between the reduced
      scattering coefficient and the volume fraction and the size of the particles is
      linearized, allowing direct reconstruction of the volume fraction of scattering
      particles in tissues. The method is validated by a series of numerical
      simulations, phantom experiments, and in vivo clinical experiments. The initial
      clinical results indicate that the volume fraction of scattering particles in a
      malignant tumor is higher than that in a benign tumor.

PMID- 18059663
TI  - Spectrally variable two-beam coupling nonlinear deconvolution.
AB  - In previous work, we introduced a dynamic range compression-based technique for
      image correction using nonlinear deconvolution; the impulse response of the
      distortion function and the distorted image are jointly transformed to pump a
      clean reference beam in a photorefractive two-beam coupling arrangement. The
      Fourier transform of the pumped reference beam contains the deconvolved image and
      its conjugate. Here we extend our work to spectrally variable dynamic range
      compression. This approach allows the retrieval of distorted signals embedded in
      a very high noise environment and does not require one to work with a very high
      beam ratio as in our previous work. Resolution recovery of blurred noisy images
      is demonstrated for several different types of image blur.

PMID- 18059664
TI  - Resonant optical transmission from a one-dimensional relief metalized
      subwavelength grating.
AB  - We have studied one-dimensional (1D) relief metalized subwavelength gratings,
      which support resonant optical transmission. We have used pregrooved DVD
      stampers, metalized with a thin Al layer. The sensitivity of resonant
      transmission of the gratings to the cladding environment was investigated by the
      help of matching fluids. We have shown that the shift of the spectral position of
      the resonance peak can be used for sensor applications, e.g., for determination
      of very low concentrations of nanosized dielectric particles in distilled water.

PMID- 18059665
TI  - Multipass pumped Nd-based thin-disk lasers: continuous-wave laser operation at
      1.06 and 0.9 microm with intracavity frequency doubling.
AB  - The laser performances of the 1.06 microm (4)F(3/2) --> (4)I(11/2) four-level
      transition and of the 0.9 microm (4)F(3/2) --> I(9/2)4 quasi-three-level
      transition were investigated using multipass pumped Nd-based media in thin-disk
      geometry. When pumping at 0.81 microm into the (4)F(5/2) level, continuous-wave
      laser operation was obtained with powers in excess of 10 W at 1.06 microm, in the
      multiwatt region at 0.91 microm in Nd:YVO(4) and Nd:GdVO(4), and at 0.95 microm
      in Nd:YAG. Intracavity frequency-doubled Nd:YVO(4) thin-disk lasers with output
      powers of 6.4 W at 532 nm and of 1.6 W at 457 nm were realized at this pumping
      wavelength. The pumping at 0.88 microm, which is directed into the (4)F(3/2)
      emitting level, was also employed, and Nd:YVO(4) and Nd:GdVO(4) thin-disk lasers
      with ~9 W output power at 1.06 microm and visible laser radiation at 0.53 microm
      with output power in excess of 4 W were realized. Frequency-doubled Nd:vanadate
      thin-disk lasers with deep blue emission at 0.46 microm were obtained under
      pumping directly into the (4)F(3/2) emitting level.

PMID- 18059666
TI  - Applications of a microlens array and a photomask to the laser microfabrication
      of a periodic photopolymer rod array.
AB  - We report the simultaneous multipoint fabrication of polymer rods by the
      femtosecond laser processing of a negative photoresist using a microlens array
      (MLA). The rods were periodically arranged in the form of an array corresponding
      to the MLA and free-standing on a glass substrate. The use of a photomask enabled
      us to define the contour of the rod array. Furthermore, sample translation
      techniques were demonstrated for the effective fabrication of large-area
      structures.

PMID- 18059667
TI  - Foam-based optical absorber for high-power laser radiometry.
AB  - We report damage threshold measurements of novel absorbers comprised of either
      liquid-cooled silicon carbide or vitreous carbon foams. The measurements
      demonstrate damage thresholds up to 1.6x10(4) W/cm(2) at an incident circular
      spot size of 2 mm with an absorbance of 96% at 1.064 microm. We present a summary
      of the damage threshold as a function of the water flow velocity and the
      absorbance measurements. We also present a qualitative description of a damage
      mechanism based on a two-phase heat transfer between the foam and the flowing
      water.

PMID- 18059668
TI  - Three-dimensional photon migration through voidlike regions and channels.
AB  - Steady-state form of the Boltzmann transport equation is solved for the
      investigation of photon propagation through three-dimensional regions and
      channels that contain a photon absorption and scattering-free fluid. Transport
      and diffusion solutions are obtained by a finite-element-spherical harmonics
      radiation transport method. Results calculated with two theories are presented in
      order to show the influence of voidlike regions and channels on the transport of
      photons.

PMID- 18059669
TI  - Detection performance of wavelet-based joint transform correlation.
AB  - The detection performance of a wavelet-based joint transform correlator (JTC) is
      studied by use of two types of images with different spatial-frequency contents
      and contrast. The simulation results show that, in comparison with an amplitude
      modulated JTC, the performance for intraclass pattern recognition can be
      optimized by using a single wavelet filter.

PMID- 18059670
TI  - Self-healing property of a caustic optical beam.
AB  - It is well known that Bessel beams and the other families of propagation
      invariant optical fields have the property of self-healing when obstructed by an
      opaque object. Here it is shown that there exists another kind of field
      distribution that can have an analog property. In particular, we demonstrate that
      a class of caustic wave fields, whose transverse intensity patterns change on
      propagation, when perturbed by an opaque object can reappear at a further plane
      as if they had not been obstructed. The physics of the phenomenon is fully
      explained and shown to be related to that of self-healing propagation invariant
      optical fields.

PMID- 18059671
TI  - Parallel optical coherence tomography system.
AB  - We present the design and procedures for implementing a parallel optical
      coherence tomography (POCT) imaging system that can be adapted to an endoscopic
      format. The POCT system consists of a single mode fiber (SMF) array with multiple
      reduced diameter (15 microm) SMFs in the sample arm with 15 microm center spacing
      between fibers. The size of the array determines the size of the transverse
      imaging field. Electronic scanning eliminates the need for mechanically scanning
      in the lateral direction. Experimental image data obtained with this system show
      the capability for parallel axial scan acquisition with lateral resolution
      comparable to mechanically scanned optical coherence tomography systems.

PMID- 18059672
TI  - Quantitative hydrogen analysis of zircaloy-4 in laser-induced breakdown
      spectroscopy with ambient helium gas.
AB  - This experiment was carried out to address the need for overcoming the
      difficulties encountered in hydrogen analysis by means of plasma emission
      spectroscopy in atmospheric ambient gas. The result of this study on zircaloy-4
      samples from a nuclear power plant demonstrates the possibility of attaining a
      very sharp emission line from impure hydrogen with a very low background and
      practical elimination of spectral contamination of hydrogen emission arising from
      surface water and water vapor in atmospheric ambient gas. This was achieved by
      employing ultrapure ambient helium gas as well as the proper defocusing of the
      laser irradiation and a large number of repeated precleaning laser shots at the
      same spot of the sample surface. Further adjustment of the gating time has led to
      significant reduction of spectral width and improvement of detection sensitivity
      to ~50 ppm. Finally, a linear calibration curve was also obtained for the
      zircaloy-4 samples with zero intercept. These results demonstrate the feasibility
      of this technique for practical in situ and quantitative analysis of hydrogen
      impurity in zircaloy-4 tubes used in a light water nuclear power plant.

PMID- 18059673
TI  - Real time diagnosis of transient pulse laser with high repetition by radial
      shearing interferometer.
AB  - Transient, high repetition pulse laser can be applied to test numerous physical
      parameters, where in situ, real time measurement and isolation of vibration is
      highly demanded. Because of its short half-width, high power, high repetition,
      and even large distortion, the laser presents unique challenges to conventional
      diagnosing methods. A system based on a novel cyclic radial shearing
      interferometer is proposed to diagnose the transient, high repetition pulse laser
      with common path, no reference plane, and high precision. With the spatial
      carrier methods, the system needs only one interferogram to reconstruct amplitude
      and wavefront of the laser. The theories of amplitude and wavefront
      reconstruction have been validated by computer simulation, and errors less than
      1/1000lambda are obtained for both. Comparing with the results of the ZYGO
      interferometer, an error less than 1/20lambda for both peak-valley and root-mean
      square values is gained with good repeatability for the wavefront. The
      calibration process and real time diagnosis of a high repetition pulse laser are
      presented then. Finally, the error consideration and system optimization are
      discussed in detail.

PMID- 18059674
TI  - Noninvasive monitoring of estrogen effects against ischemic stroke in rats by
      near-infrared spectroscopy.
AB  - The aim of this study was to assess hemodynamic changes by near-infrared
      spectroscopy (NIRS) during acute focal cerebral ischemia and reperfusion. The
      study also has evaluated the therapeutic effects of estrogen against vascular
      dysfunction. Focal cerebral ischemia was induced in nine bilaterally
      ovariectomized rats, using an endovascular occlusion technique of the middle
      cerebral artery (MCA). Four out of nine rats had estrogen pretreatment before MCA
      occlusion (MCAO). The other five rats had MCAO with no pretreatment. The
      occlusion time was 60 min, followed by 40-60 min of reperfusion. Real-time
      monitoring of changes in hemoglobin concentrations was performed by a steady
      state, two-channel, NIRS system through the period of occlusion and reperfusion.
      Both changes in total and oxygenated hemoglobin concentrations (D[HbT] and
      D[HbO(2)]) display apparent periodic fluctuations during occlusion for the rats
      without estrogen pretreatment, while no rhythmic fluctuation was observed in the
      rats with the pretreatment. This rhythmic fluctuation is a microvascular
      dysfunction. Fourier power spectral analysis was performed on the D[HbO(2)]
      profiles in both rat groups. The results show that the cumulative frequency power
      of D[HbO(2)] in the range of 0.0025-0.01 Hz for the rats without pretreatment is
      significantly higher than that with pretreatment. The study implies that the
      dysfunctional fluctuations disappear in the rats with estrogen pretreatment,
      demonstrating a new application of NIRS, i.e., to detect focal cerebral ischemia
      and to monitor cerebral responses to therapy against vascular dysfunction in
      animal models.

PMID- 18059675
TI  - Quantification of the evaporative cooling in an ethanol spray created by a
      gasoline direct-injection system measured by multiline NO-LIF gas-temperature
      imaging.
AB  - Two-dimensional gas-phase temperature fields were quantitatively measured in an
      evaporating ethanol spray with multiline excitation thermometry based on laser
      induced fluorescence of nitric oxide (NO-LIF). This technique yields absolute
      temperature fields without calibration and simultaneously detects the spray
      position. The accuracy of the presented temperature measurements is +/-1 K.
      Systematic errors of the scanned multiline thermometry approach due to time
      averaging in turbulent systems were investigated and found to be negligible. The
      pulsed spray was generated by a gasoline direct-injection nozzle with swirl
      injecting ethanol into air in a flow cell at room temperature and atmospheric
      pressure. The gas temperature inside the spray cloud was found to decrease by 10
      K at approximately 5-10 ms after injection. Different injection pressures
      influence the evaporation behavior.

PMID- 18059676
TI  - Automated tongue segmentation in hyperspectral images for medicine.
AB  - Automatic tongue area segmentation is crucial for computer aided tongue
      diagnosis, but traditional intensity-based segmentation methods that make use of
      monochromatic images cannot provide accurate and robust results. We propose a
      novel tongue segmentation method that uses hyperspectral images and the support
      vector machine. This method combines spatial and spectral information to analyze
      the medical tongue image and can provide much better tongue segmentation results.
      The promising experimental results and quantitative evaluations demonstrate that
      our method can provide much better performance than the traditional method.

PMID- 18059677
TI  - Binary phase-only filtering for turbulence compensation in fiber-coupled free
      space laser communication systems.
AB  - Binary wavefront control in the focal plane (i.e., binary phase-only filtering)
      for partial compensation of atmospheric turbulence in fiber-coupled free-space
      laser communication systems is investigated. Numerical results from wave-optics
      simulations show that in an air-to-air scenario, the combination of binary phase
      only filtering and centroid tracking provides mean fiber coupling efficiency
      close to that resulting from ideal least-squares adaptive optics, but without the
      requirement for direct wavefront sensing. This result suggests a simpler and less
      computationally demanding turbulence mitigation system that is more readily
      applied to tactical applications.

PMID- 18059678
TI  - Effective formation method for an aspherical microlens array based on an
      aperiodic moving mask during exposure.
AB  - An aperiodic mask design method for fabricating a microlens array with an
      aspherical profile is proposed. The nonlinear relationship between exposure doses
      and lens profile is considered, and the select criteria of quantization interval
      and fabrication range of the method are given. The mask function of a quadrangle
      microlens array with a hyperboloid profile used in the infrared was constructed
      by using this method. The microlens array can be effectively fabricated during a
      one time exposure process using the mask. Reactive ion etching was carried out to
      transfer the structure into the substrate of germanium. The measurement results
      indicate that the roughness is less than 10 nm (pv), and the profile error is
      less than 40 nm (rms).

PMID- 18059679
TI  - Optical anisotropy of the human cornea determined with a polarizing microscope.
AB  - We have investigated the optical anisotropy of the human cornea using a
      polarizing microscope normally used for optical mineralogy studies. The central
      part of the cornea was removed from 14 eyes (seven donors). With the sample
      placed on the microscope stage, we consistently observed hyperbolic isogyres
      characteristic of a negative biaxial material. The angle between the optic axes,
      generally similar in both eyes, ranged from 12 degrees to 40 degrees (mean+/
      SD=31 degrees +/-8 degrees ). The optic axial plane always inclined downward in
      the nasal direction at 1 degrees -45 degrees below the horizontal (mean+/-SD=22+/
      13 degrees ). The retardance produced by the corneas was estimated to be less
      than 200 nm. In conclusion, the human cornea possesses the anisotropy of a
      negative biaxial material. Both the angle between the optic axes and the
      retardance were fairly constant among the majority of samples, suggestive of
      uniformity in corneal structure.

PMID- 18059680
TI  - Injection seeded frequency stabilized Nd:YAG ring oscillator following a Pound
      Drever-Hall scheme.
AB  - An injection seeded Nd:YAG laser oscillator has been set up and frequency
      stabilized following an rf-sideband scheme. This dual rod oscillator emits pulses
      with 23 ns duration and 20 mJ energy. The beam quality is almost diffraction
      limited (M(2)=1.2). The frequency stability was characterized with a heterodyne
      method to 1.0 MHz root mean square (rms). This oscillator will serve as the front
      end for a series of lidar devices for spectrally sensitive measurements.

PMID- 18059681
TI  - Polarization components analysis for invariant discrimination.
AB  - Linear and nonlinear components analysis of data from a monostatic laser
      polarimeter is developed and applied to the task of remote, nonimaging
      discrimination among different textures on paint and polymer coupons independent
      of their spatial orientations. Both principal-components analysis and nonlinear
      components analysis are applied to multidimensional laser data in measured
      Mueller matrices, with discrimination via cluster segmentation in derived linear
      and nonlinear constant channels. Textures on the discriminated coupons are
      generated by heating and illustrated in optical micrographs.

PMID- 18059682
TI  - Temperature distribution in dental tissue after interaction with femtosecond
      laser pulses.
AB  - Algebraic and numerical solutions are presented of the temperature rise in dental
      tissue due to interaction with ultrashort optical radiation. Results of the
      studies with femtosecond laser pulses show agreement between theory and
      experiment. A temperature rise of typically 5 K is found for a 40 millisecond
      train of 7 nJ, 70 fs laser pulses at a repetition rate of 80 MHz. The peak
      irradiance in our experimental studies was limited to 3x10(6) W/cm(2).
      Applications include photoacoustic imaging and tomography of dental tissue.

PMID- 18059683
TI  - Optical system for tablet variety discrimination using visible/near-infrared
      spectroscopy.
AB  - An optical system based on visible/near-infrared spectroscopy (Vis/NIRS) for
      variety discrimination of ginkgo (Ginkgo biloba L.) tablets was developed. This
      system consisted of a light source, beam splitter system, sample chamber, optical
      detector (diffuse reflection detector), and data collection. The tablet varieties
      used in the research include Da na kang, Xin bang, Tian bao ning, Yi kang, Hua na
      xing, Dou le, Lv yuan, Hai wang, and Ji yao. All samples (n=270) were scanned in
      the Vis/NIR region between 325 and 1075 nm using a spectrograph. The chemometrics
      method of principal component artificial neural network (PC-ANN) was used to
      establish discrimination models of them. In PC-ANN models, the scores of the
      principal components were chosen as the input nodes for the input layer of ANN,
      and the best discrimination rate of 91.1% was reached. Principal component
      analysis was also executed to select several optimal wavelengths based on loading
      values. Wavelengths at 481, 458, 466, 570, 1000, 662, and 400 nm were then used
      as the input data of stepwise multiple linear regression, the regression equation
      of ginkgo tablets was obtained, and the discrimination rate was researched 84.4%.
      The results indicated that this optical system could be applied to discriminating
      ginkgo (Ginkgo biloba L.) tablets, and it supplied a new method for fast ginkgo
      tablet variety discrimination.

PMID- 18059685
TI  - Beam analysis by fractional Fourier transform.
AB  - A method of spatial modal decomposition for optical beams by fractional Fourier
      transform, and its practical implementation with reduced complexity by use of
      modal interleavers, are discussed.

PMID- 18059684
TI  - Sequence of phase correction in multiconjugate adaptive optics.
AB  - The way in which the sequence of phase correction impinges on performance in
      multiconjugate adaptive optics systems is described. When multiple phase
      modulators with different conjugate ranges are used, the conjugate images of the
      phase modulators in the atmosphere must be reimaged in the reverse order post
      focus, and adaptive phase correction applied in this sequence for perfect
      amplitude and phase cancellation. Performing the correction without relay optics
      results in residual amplitude and phase aberrations. It is shown, by Monte Carlo
      simulations of Fresnel propagation, that the effects of wave optical propagation
      become nonnegligible at visible wavelengths and for large air masses.

PMID- 18059686
TI  - Interference approach applied to dual-grating dielectric resonant grating
      reflection filters.
AB  - The resonant mechanisms associated with dual-grating dielectric resonant grating
      reflection filters are described by use of an interference approach. These
      structures consist of two modulated regions of equal period separated by a higher
      index film region. We show that the spectral linewidth is dependent on the
      separation between the modulated regions and can range from theoretically zero to
      approximately four times what would be obtained by use of a single-grating
      geometry.

PMID- 18059687
TI  - Transfer of continuous-relief diffractive structures into diamond by use of
      inductively coupled plasma dry etching.
AB  - The transfer of continuous-relief diffractive structures from resist into diamond
      by use of direct-write electron-beam lithography followed by dry etching in an
      inductively coupled plasma is demonstrated. The gases used for the diamond
      etching are O(2) and Ar. The chemical-vapor-deposited diamond substrate is of
      optical quality. Our results show that the transfer process generates fairly
      smooth etched structures. Blazed gratings with periods of 45mum and Fresnel
      lenses have been manufactured. The blazed gratings have been optically evaluated
      with a femtosecond laser operating at 400 nm. The diffraction efficiency was 68%
      in the first order, with a theoretical value of 100%. We intend to investigate
      the transfer process further and then to fabricate diffractive and refractive
      elements for use with Nd:YAG high-power lasers.

PMID- 18059688
TI  - Sensitivity characteristics near the dispersion turning points of long-period
      fiber gratings in B/Ge codoped fiber.
AB  - We report a theoretical and experimental investigation of the dispersion property
      of long-period fiber gratings in B/Ge codoped fiber. A novel concept of a mode
      ultrasensitive zone defined by a region in which the phase-matching conditions
      are close to the dispersion turning points is proposed. The transition from a
      dual-resonance state to a dispersion turning point is revealed for a set of
      ultrasensitive-zone gratings during the UV-writing process. We explore the
      sensitivity characteristics near the dispersion turning points, with the aim of
      implementing two types of temperature sensor with sensitivity 2 orders of
      magnitude higher than that of the conventional long-period gratings.

PMID- 18059689
TI  - Ultrashort-pulse investigation of the propagation properties of the LP(11) mode
      in 1.55-mum communication fibers.
AB  - The coupling of an ultrashort laser pulse into a single-mode optical
      communication fiber gives rise to two propagating pulses as a result of the
      excitation of two guided modes, the fundamental, LP(01) , and the leaky, LP(11) .
      Such a phenomenon provides a new approach to the study of the propagation
      properties of the LP(11) mode. An experiment with tunable 110-fs pulses at a
      wavelength near 1550 nm is described. Information about the group velocity, the
      polarization-rotation length, the attenuation coefficient, and the cutoff
      wavelength of the LP(11) mode is obtained in a simple and direct way for various
      fibers.

PMID- 18059690
TI  - Nonlinear chirp of dispersion-managed return-to-zero pulses.
AB  - Applying variational methods, we derive a reduced system of equations from the
      nonlocal equation that governs the average dynamics in dispersion-managed
      systems. These equations, which apply for any type of return-to-zero pulse,
      describe the stroboscopic evolution of the pulse parameters and bypass the fast
      variations inside each dispersion map. In the limit of large map strength we
      integrate the equations to obtain explicitly formulas for the parameters of a
      chirped return-to-zero pulse as well as the amount of post-transmission
      compensation needed to restore the initial pulse width.

PMID- 18059691
TI  - Multiple beam interference in a quadrupolar glass fiber.
AB  - Motivated by the recent observation of periodic filter characteristics of an oval
      shaped microcavity, we study the possible interference of multiple beams in the
      far field of a laser-illuminated quadrupolar glass fiber. From numerical ray
      tracing simulations we obtain the interference-relevant length-difference
      spectrum and compare it with data extracted from the experimental filter results.
      Our analysis reveals that different polygonal cavity modes that are refractively
      output coupled in the high-curvature region of the fiber contribute to the
      observed far-field interference.

PMID- 18059692
TI  - Dynamic studies of holographic gratings in dye-doped liquid-crystal films.
AB  - The dynamic behavior of a holographic grating induced in a homeotropically
      aligned dye-doped liquid-crystal film is investigated. In the presence of an
      applied dc voltage, photoexcited azo dyes induce a photorefractive grating and
      then diffuse and are adsorbed onto cell substrates. The reorientation of liquid
      crystals as a result of adsorbed dyes leads to a phase grating that is phase
      shifted 90 degrees from the photorefractive grating. Competition of these two
      gratings induces two-beam coupling of the writing beams, initially transferring
      energy from beam 1 to beam 2 and then, after a pause, from beam 2 to beam 1.

PMID- 18059693
TI  - Power-excitation diffraction tomography with partially coherent light.
AB  - Some consequences of using partially coherent fields in the recently proposed
      method of power-extinction diffraction tomography are analyzed. It is found that
      the method is very tolerant of short spectral coherence lengths. The spectral
      coherence length of the field is shown to set the scale of a low-pass filter that
      acts on the subject. The implications of these results for implementation of the
      method are discussed.

PMID- 18059694
TI  - Arrays of silicon microdischarge devices with multicomponent dielectrics.
AB  - Arrays as large as 15x15 of microdischarge devices having inverted pyramidal
      silicon cathodes (50mumx50mum) and SiO(2)- Si(3)N(4)- polymer composite
      dielectrics have been fabricated and characterized with Ne gas. The lifetimes,
      reliability, and ignition characteristics of the arrays are superior to those of
      earlier designs having a single polymer dielectric. Operating voltages as low as
      150 V for a 10x10 pixel array and 1000 Torr of Ne have been measured. Single
      (50mumx50mum) pyramidal cathode devices operate at voltages as low as 113 V when
      the Ne pressure is 900 Torr.

PMID- 18059695
TI  - Simple ABCD matrix treatment for transversely varying saturable gain.
AB  - We have developed an ABCD matrix that, for the first time to our knowledge,
      accurately describes the transformation of a Gaussian beam by a medium with
      transversely varying saturable gain. In contrast with the conventional ABCD
      matrix, the newly developed matrix is shown to be in excellent agreement with a
      full beam propagation code over a wide parameter range. Accurate treatment of
      transversely varying saturable gain in laser resonators is important for the
      optimization of end-pumped lasers, particularly for efficient diode-pumped solid
      state and Kerr-lens mode-locked systems.

PMID- 18059696
TI  - Measurement of pulse width and amplitude jitter noises of gigahertz optical pulse
      trains by time-domain demodulation.
AB  - We propose a technique for measuring both pulse width and amplitude jitter noises
      of high-repetition-rate optical pulse trains and the cross correlation between
      these noises as well. The technique is based on time-domain amplitude
      demodulation of three harmonic components of the detected pulse train. We applied
      this technique to characterize noises of a gigahertz optical pulse train
      generated by an actively mode-locked Er-doped fiber laser. Correlation between
      pulse width jitter and pulse amplitude jitter was observed at low frequencies in
      this laser. Unlike relaxation oscillation noise, low-frequency noise is free from
      pulse energy jitter. Owing to its ability to measure pulse width jitter in
      addition to amplitude and phase jitters, this technique is of great interest for
      characterizing noises of a wide variety of optical pulse train sources.

PMID- 18059697
TI  - Rapid near-infrared Raman spectroscopy system for real-time in vivo skin
      measurements.
AB  - A rapid dispersive-type near-infrared (NIR) Raman spectroscopy system and a Raman
      probe were developed to facilitate real-time, noninvasive, in vivo human skin
      measurements. Spectrograph image aberration was corrected by a parabolic-line
      fiber array, permitting complete CCD vertical binning, thereby yielding a 3.3-16
      fold improvement in signal-to-noise ratio. Good quality in vivo cutaneous NIR
      Raman spectra free of interference from fiber fluorescence and silica Raman
      scattering can be acquired in less than 1 s, which greatly facilitates practical
      noninvasive tissue characterization and clinical diagnosis.

PMID- 18059698
TI  - Efficient second-harmonic generation in birefringently phase-matched
      GaAs/Al(2)O(3) waveguides.
AB  - We report efficient second-harmonic generation of femtosecond pulses in
      birefringently phase-matched GaAs/Al(2)O(3) waveguides pumped at 2.01mum. By use
      of pump pulses of ~200-fs duration and type I interaction, practical second
      harmonic average powers of up to ~650muW were obtained, with an average input
      power of ~50muW. Waveguides of four different widths and two different lengths
      were investigated, and a normalized conversion efficiency of greater than 1000%W(
      1)cm(-2) was obtained for a 1-mm waveguide. Measurements of pump and second
      harmonic spectra provided clear evidence of phase matching and depletion of the
      pump spectrum. The measured bandwidth of the second harmonic was ~1.3nm. From the
      measurements of transmitted pump power at the phase-matching wavelength, pump
      depletions of more than 80% were recorded.

PMID- 18059699
TI  - Nonlinear response and optical limiting in SrBi(2)Ta(2)O(9) thin films.
AB  - SrBi(2)Ta(2)O(9) (SBT) thin films on quartz substrates were prepared by use of
      the pulsed-laser deposition technique. The nonlinear refractive indices, n(2) ,
      of the SBT films were measured by use of z-scan techniques with picosecond
      pulses. Large negative nonlinear refractive indices of 3.84 and 3.58cm(2)/GW were
      obtained for the wavelengths 532 nm and 1.064mum , respectively. The two-photon
      absorption coefficient was determined to be 7.3 cm/GW for 532 nm. The limiting
      behavior of SBT thin film on a quartz substrate was investigated in an f/5
      defocusing geometry by use of 38-ps-duration, 532-nm, 1.064mum laser excitation.

PMID- 18059700
TI  - Incoherent spatial solitary waves in nematic liquid crystals.
AB  - (2+1) -dimensional spatial solitary waves are generated by launching of milliwatt
      power linearly polarized light beams in voltage-biased planar cells with undoped
      nematic liquid crystals, regardless of the degree of spatial coherence of the
      input. Coherent and incoherent self-trapping, as well as guidance of a weaker
      copolarized signal, is demonstrated.

PMID- 18059701
TI  - Single-frequency mid-infrared optical parametric oscillator source for coherent
      laser radar.
AB  - We report on the design and characterization of a highly coherent mid-IR source
      at 3.57mum based on a single-frequency optical parametric oscillator. Detailed
      frequency and amplitude noise spectra have been measured. The rms intensity noise
      from 1.2 to 1000 Hz was 0.03%, and a rms frequency drift of 8 kHz in 1 ms was
      observed. We have also demonstrated the utility of this source for coherent laser
      radar applications by measuring micro-Doppler spectra from vibrating targets.

PMID- 18059702
TI  - Optical representation of binary data based on both intensity and phase
      modulation with a twisted-nematic liquid-crystal display for holographic digital
      data storage.
AB  - We propose a method of representing binary data by modulating both the intensity
      and the phase of beams with a twisted-nematic liquid-crystal display. With our
      method it is possible to reduce the dc component of the data image and thus
      improve the beam-intensity uniformity at the holographic recording plane when one
      is recording Fourier-plane holograms to obtain maximal areal storage density in
      disk-shaped storage media. The feasibility of our method is demonstrated
      experimentally.

PMID- 18059703
TI  - Recording of optical near fields in remote locations by near-field holography.
AB  - We propose a method of near-field recording in a space that is quite apart from
      the original source (generator) of optical near fields. The method is based on
      the recently developed technique of near-field holography. Experiments based on
      our method have shown that near fields that originate from sub-diffraction-limit
      sized objects can be stored in a photorefractive crystal 2 mm apart from the
      crystal surface, resulting in the retrieval of sub-diffraction-limit-sized spots.
      This means that our scheme can provide a method for multilayer (stackwise) near
      field storage and, thus, contribute to a significant enhancement of the storage
      capacity of near-field optical memory.

PMID- 18059704
TI  - Elliptic vortices of electromagnetic wave fields.
AB  - We demonstrate the existence of elliptic vortices of electromagnetic scalar wave
      fields. The corresponding intensity profiles are formed by propagation-invariant
      confocal elliptic rings. We have found that copropagation of this kind of vortex
      occurs without interaction. The results presented here also apply for physical
      systems described by the (2+1) -dimensional Schrodinger equation.

PMID- 18059705
TI  - Generation of two-color femtosecond pulses by self-synchronizing Ti:sapphire and
      Cr:forsterite lasers.
AB  - We report a novel technique for the synchronization of two different femtosecond
      solid-state lasers by crossing of both laser pulses in a Kerr medium. Stable dual
      wavelength femtosecond pulses at central wavelengths of 820 and 1250 nm have been
      obtained. The tolerance of cavity-length mismatch is ~0.6mum , where the pulse
      widths of the Ti:sapphire and the Cr:forsterite lasers are 18 and 40 fs,
      respectively, at average powers of 600 and 110 mW. The typical timing jitter
      derived from the cross correlation is less than 3 fs.

PMID- 18059706
TI  - Self-starting stretched-pulse fiber laser mode locked and stabilized with slow
      and fast semiconductor saturable absorbers.
AB  - A self-starting stretched-pulse mode-locked erbium-doped fiber laser that uses
      fast and slow semiconductor saturable absorbers is described. By using two
      absorbers, we obtained reliable operation at a fundamental repetition rate with
      250 pJ of pulse energy without multiple-pulse breakup. External chirp
      compensation was used to compress the highly chirped pulses to durations of 135
      fs.

PMID- 18059707
TI  - Generation and amplification of ultrashort shaped pulses in the visible by a two
      stage noncollinear optical parametric process.
AB  - We report the generation and amplification of ultrashort shaped pulses in the
      visible by a two-stage noncollinear optical parametric amplification process.
      Phase and amplitude profiles of the shaped pulses are conserved in our
      amplification scheme. The energy losses normally associated with the production
      of complex shaped pulses are eliminated.

PMID- 18059708
TI  - Effective noise in thresholded intensity distribution: influence on centroid
      statistics.
AB  - It is usual to preprocess data before reduction, but it is not so common to study
      how this operation affects the final results. Determination of the centroid is a
      relevant task for many optical measurement devices, and the centroid is very
      often calculated over thresholded data. The influence of preprocessing
      thresholding algorithms on the statistical properties of intensity data affected
      by additive Gaussian noise is described as a different effective additive signal
      perturbation. Theoretical, simulated, and experimental analyses of the model of
      the effective noise were performed, and good agreement among the analyses was
      obtained. Direct extension of the analyses from the influence of preprocessing to
      centroid determination is also presented.

PMID- 18059709
TI  - Harnessing caustics for wave-front sensing.
AB  - Scintillation in measured wave fronts adds spurious dislocations and deformations
      to their reconstruction. The source of the problem is caustics formed by
      aberrations in intermediate planes. I propose to use intentional caustics to
      measure wave fronts under severe conditions such as low light level, fast scale
      variations, large aberrations, and discontinuities in the wave front. A simple
      realization is based on the Hartmann-Shack sensor, which samples the wave front
      with a lenslet array. Movement of the lenslets' foci is linear with slope
      changes. Here the lenslets are effectively formed in an acousto-optic device: Two
      standing waves are launched perpendicularly to the light beam and to each other.
      At some distance down the beam, each wave creates a comb of caustics, and the two
      orthogonal combs add up to an array of caustic spots. The spatial frequency of
      the array is linear with the temporal frequency of the standing sound waves. A
      simple Fourier demodulation scheme supplies the two wave-front gradients.

PMID- 18059710
TI  - Resonator-enhanced optical dipole trap for fermionic lithium atoms.
AB  - We demonstrate a novel optical dipole trap that is based on enhancement of the
      optical power density of a Nd:YAG laser beam in a resonator. The trap is
      particularly suited for experiments with ultracold gases, as it combines a
      potential depth of the order of 1 mK with storage times of several tens of
      seconds. We study the interactions in a gas of fermionic lithium atoms in our
      trap and observe the influence of spin-changing collisions and off-resonant
      photon scattering. A key element in reaching long storage times is the use of an
      ultralow-noise laser. The dependence of storage time on laser noise is
      investigated.

PMID- 18059711
TI  - Submicrometer fiber-optic Fabry-Perot interferometer formed by use of the
      Langmuir-Blodgett technique.
AB  - The fabrication of an optical cavity at the distal end of an optical fiber has
      been achieved by Langmuir-Blodgett (LB) deposition of tricosanoic acid. This
      technique allows nanometer-scale control over the cavity length to a total
      thickness of ~0.5 microm . The cavity has been shown to act interferometrically
      and, thus, has potential sensing applications.

PMID- 18059712
TI  - Message encoding-decoding at 2.5 Gbits/s through synchronization of chaotic
      pulsing semiconductor lasers.
AB  - Chaotic optical communication with fast chaotic pulsing semiconductor lasers is
      experimentally demonstrated. Both a pulse stream at a 500-MHz repetition rate and
      a pseudorandom bit sequence at a 2.5-Gbit/s bit rate are successfully
      transmitted. The quality of synchronization in a chaos-modulation scheme is
      examined. The quality of message recovery is correlated to the quality of chaos
      synchronization.

PMID- 18059713
TI  - Intrachannel pulse interactions in dispersion-managed transmission systems:
      timing shifts.
AB  - Nonlinear intrachannel interactions responsible for timing shifts in a
      transmission system with strong periodic dispersion management are investigated.
      Formulas describing the evolution of the timing shift are obtained for general
      bit patterns. When average dispersion is negligible, the timing shift is shown to
      grow linearly in distance in a system with loss and lumped amplification, whereas
      in a lossless system the timing shift is sufficiently small at every chirp-free
      point. The analysis agrees with direct numerical simulations.

PMID- 18059714
TI  - High-average-power picosecond Yb-doped fiber amplifier.
AB  - We report on a cladding-pumped, ytterbium-doped large-core-area fiber amplifier
      that is capable of generating 51.2 W of average power at a 1064-nm center
      wavelength, an 80-MHz repetition rate, and a 10-ps pulse duration. In an
      ytterbium-doped large-mode-area fiber these pulses could be amplified up to 43.2
      W with diffraction-limited beam quality (M(2)~1.3) . Power scaling limitations
      that arise from nonlinear distortions such as self-phase modulation and
      stimulated Raman scattering are discussed.

PMID- 18059715
TI  - Optical snake-based segmentation processor with a shadow-casting incoherent
      correlator.
AB  - What is believed to be the first incoherent snake-based optoelectronic processor
      that is able to segment an object in a real image is described. The process,
      based on active contours (snakes), consists of correlating adaptive binary
      references with the scene image. The proposed optical implementation of
      algorithms that are already operational numerically opens attractive
      possibilities for faster processing. Furthermore, this experiment has yielded a
      new, versatile application for optical processors.

PMID- 18059716
TI  - Hypersensitization of rare-earth-doped waveguides for distributed-feedback
      amplifier and laser applications.
AB  - Deterioration of the gain coefficient as a result of UV processing of hydrogen
      loaded Er(3+) - and Er(3+)/Yb (3+) -doped silicate optical waveguides can be
      reduced by initial hypersensitization of the waveguide prior to bulk irradiation.
      This allows improved performance in active-grating devices such as distributed
      feedback fiber amplifiers and lasers.

PMID- 18059717
TI  - Formation of a microfiber bundle by interference of three noncoplanar beams.
AB  - A systematic analysis of interference of three noncoplanar plane waves with
      identical frequency is provided. This analysis shows that a fiber bundle with
      spacing of the order of the wavelength, which one may conveniently control by
      changing the recording geometry, can be formed by this means. The relation
      between the incident light-wave vectors and the resultant pattern is analyzed.
      The concept of uniform contrast for an interference pattern is introduced, and
      the polarization optimization approach for each beam that ensures maximum uniform
      contrast for each beam is also given.

PMID- 18059718
TI  - One-dimensional iterative algorithm for three-dimensional point-spread function
      engineering.
AB  - We present a new method with which to binarize pupil filters designed to control
      the three-dimensional irradiance distribution in the focal volume of an optical
      system. The method is based on a one-dimensional iterative algorithm, which
      results in efficient use of computation time and in simple, easy to fabricate
      binary filters. An acceptable degree of resemblance between the point-spread
      function of the annular binary filter and that of its gray-tone counterpart is
      obtained.

PMID- 18059719
TI  - Differential phase measurements in low-coherence interferometry without 2pi
      ambiguity.
AB  - Quantitative phase measurements by low-coherence interferometry and optical
      coherence tomography are restricted by the well-known 2pi ambiguity to path
      length differences smaller than lambda/2 . We present a method that overcomes
      this ambiguity. Introducing a slight dispersion imbalance between reference and
      sample arms of the interferometer causes the short and long wavelengths of the
      source spectrum to separate within the interferometric signal. This causes the
      phase slope to vary within the signal. The phase-difference function between two
      adjacent sample beam components is calculated by subtraction of their phase
      functions obtained from phase-sensitive interferometric signal recording. Because
      of the dispersive effect, the phase difference varies across the interferometric
      signal. The slope of that phase difference is proportional to the optical path
      difference, without 2pi ambiguity.

PMID- 18059720
TI  - Measurement of fiber-cladding diameter uniformity by use of whispering-gallery
      modes: nanometer resolution in diameter variations along millimeter to centimeter
      lengths.
AB  - Variations in fiber-cladding diameter on a nanometer scale were measured along
      millimeter to centimeter lengths by use of whispering-gallery modes (WGMs) in the
      elastic scattering of the fiber. The fiber was side coupled with a wavelength
      tunable Gaussian beam. The scattered light was imaged approximately 1:1 onto a
      multichannel photodiode array detector. Based on the WGM wavelength shifts along
      the fiber, the taper of the fiber cladding's diameter was measured on a
      nanometer/millimeter scale. The fiber's surface roughness amplitude (in
      nanometers) and granular size ( approximately 100 microm) along centimeter-length
      fibers could also be revealed by use of higher- Q resonances.

PMID- 18059721
TI  - OH sensor based on ultraviolet, continuous-wave absorption spectroscopy utilizing
      a frequency-quadrupled, fiber-amplified external-cavity diode laser.
AB  - The development of an all-solid-state cw laser system for optical absorption
      measurements of the OH radical in the UV spectral range is described. The tunable
      output of a 1064-nm external-cavity diode laser is amplified by use of a
      Nd:doped, double-clad fiber amplifier. The amplified near-IR radiation is
      frequency doubled by a periodically poled lithium niobate crystal and then
      quadrupled in a beta-barium borate crystal. The design and operation of the
      system and measurements of OH absorption in the (2, 0) band of the A(2)?(+)-
      X(2)? electronic transition are discussed.

PMID- 18059722
TI  - Sinusoidally phase-modulated interference microscope for high-speed high
      resolution topographic imagery.
AB  - We describe an interference microscope that produces topographic images with a
      minimum acquisition time of 20 ms. The system is based on phase-shifting
      interferometry with sinusoidal phase modulation induced by the oscillation of an
      interferometric objective (Michelson or Mirau). A CCD camera captures four images
      per oscillation period to produce a phase map in real time. The system is
      installed on a commercial microscope.

PMID- 18059723
TI  - Minimizing bending losses in two-dimensional discrete soliton networks.
AB  - We show that reflection losses suffered by discrete solitons along sharp bends in
      two-dimensional waveguide-array networks can be almost eliminated. Analysis
      indicates that this can be accomplished by appropriately engineering the corner
      site of the bend. Our analytical results are verified by numerical simulations.

PMID- 18059724
TI  - Spatial modulation instability in a Kerr slab waveguide.
AB  - We report the observation of noise-initiated modulational instability in AlGaAs
      slab waveguides at 1.55 microm . Experiments were performed with the local,
      ultrafast Kerr nonlinearity at half the bandgap. The agreement between experiment
      and theory for the periodicity versus intensity was good.

PMID- 18059725
TI  - Widely and continuously tunable optical parametric oscillator based on a
      cylindrical periodically poled KTiOPO(4) crystal.
AB  - We report on what is to our knowledge the first realization of a quasi-phase
      matched optical parametric oscillator (OPO) based on a crystal with a cylindrical
      shape. The main reason for interest in this device is its broad, continuous
      tuning. In experiments with a 1064-nm pump, the signal tuning range was equal to
      525 nm (1515-2040 nm), and the corresponding idler was continuously tuned over
      1340 nm (2220-3560 nm). The angular tuning was 26 degrees , with only a minor
      variation of the OPO threshold over the entire tuning range.

PMID- 18059726
TI  - High-average-power (15-W) 255-nm source based on second-harmonic generation of a
      copper laser master oscillator power amplifier system in cesium lithium borate.
AB  - We have generated 15 W of UV (255-nm) radiation with an optical conversion
      efficiency of 28% by frequency doubling the 510.6-nm output of a high-beam
      quality, high-power copper laser system in cesium borate lithium (CLBO). We found
      that the superior performance of CLBO relative to beta-barium borate is
      attributable largely to the small UV absorption and wide temperature acceptance
      bandwidth of CLBO, which reduces thermal dephasing during high-power UV
      generation.

PMID- 18059727
TI  - Fabrication of ultralow-loss Si/SiO(2) waveguides by roughness reduction.
AB  - We demonstrate 0.8-dB/cm transmission loss for a single-mode, strip Si/SiO(2)
      waveguide with submicrometer cross-sectional dimensions. We compare the
      conventional waveguide-fabrication method with two smoothing technologies that we
      have developed, oxidation smoothing and anisotropic etching. We observe
      significant reduction of sidewall roughness with our smoothing technologies,
      which directly results in reduced scattering losses. The rapid increase in the
      scattering losses as the waveguide dimension is miniaturized, as seen in
      conventionally fabricated waveguides, is effectively suppressed in the waveguides
      made with our smoothing technologies. In the oxidation smoothing case, the loss
      is reduced from 32 dB/cm for the conventional fabrication method to 0.8 dB/cm for
      the single-mode waveguide width of 0.5 microm . This is to our knowledge the
      smallest reported loss for a high-index-difference system such as a Si/SiO(2)
      strip waveguide.

PMID- 18059728
TI  - Bunching and antibunching in the fluorescence of semiconductor nanocrystals.
AB  - The fluorescence of single-colloidal CdSe quantum dots is investigated at room
      temperature by means of the autocorrelation function over a time scale of almost
      12 orders of magnitude. Over a short time scale, the autocorrelation function
      shows complete antibunching, indicating single-photon emission and atomiclike
      behavior. Over longer time scales (up to tens of seconds), we measure a bunching
      effect that is due to fluorescence intermittency and that cannot be described by
      fluctuations between two states with constant rates. The autocorrelation function
      also exhibits nonstationary behavior related to power-law distributions of On and
      Off times.

PMID- 18059729
TI  - High-spectral-resolution stimulated Rayleigh-Brillouin scattering at 1 microm.
AB  - We have demonstrated stimulated Rayleigh-Brillouin scattering at a wavelength of
      1.064 microm , using an injection-seeded Nd:YAG laser as a pump laser and a
      tunable diode laser as a probe laser. Spectra with a good signal-to-noise ratio
      are obtained despite the low probe-beam power and small gain coefficient in the
      infrared. Stimulated Rayleigh scattering is readily observable in organic and
      many other liquids because of absorption by the OH and CH overtone or combination
      bands. The absorption also causes an asymmetry in the stimulated Brillouin peak.
      A Rayleigh linewidth of 8 MHz is measured with this approach.

PMID- 18059730
TI  - Laser cooling of calcium ions by use of ultraviolet laser diodes: significant
      induction of electron-shelving transitions.
AB  - Calcium ions are laser cooled in a Paul trap by use of a grating-stabilized UV
      laser diode. Unusual quantum jumps or fluctuations in the fluorescence signal are
      observed without application of any shelving lasers. It has become clear that
      such phenomena can be ascribed to shelving transitions induced by background 393
      nm spontaneous photons emitted from the laser medium. Shelving transitions are
      suppressed by use of an interference filter, and the ions are successfully cooled
      to crystallization temperature with sufficient reproducibility.

PMID- 18059731
TI  - Incidence-angle selection and spatial reshaping of terahertz pulses in optical
      tunneling.
AB  - We present spatially resolved measurements of the electric field of terahertz
      pulses undergoing optical tunneling that show strong pulse reshaping in both time
      and space. This reshaping is shown to be a result of frequency and incidence
      angle filtering of the complex amplitude of the plane-wave basis set that makes
      up the pulse. This filtering leads to spreading of the pulse in the time and
      space dimensions, as expected from linear dispersion theory. Measurement of the
      pulse shape after transmission through an optical tunneling barrier permits
      direct determination of the complex system transfer function in two dimensions.
      The transfer function, measured over both thin and thick barrier limits, contains
      a complete description of the tunneling barrier system from which the phase and
      loss times can be directly determined.

PMID- 18059732
TI  - Direct measurement of the quality factor in a two-dimensional photonic-crystal
      microcavity.
AB  - A new microcavity design is proposed and structures are realized with a two
      dimensional photonic-crystal slab. The cavity consists of seven defect holes that
      encompass a hexagon and is designed to reduce vertical light leakage. From a
      direct transmission measurement, a Q value of 816+/-30 is achieved at lambda
      =1.55 mum . This high- Q cavity will permit the realistic realization of
      spontaneous-emission modification and on-off optical switches.

PMID- 18059733
TI  - Intraluminal fiber-optic Doppler imaging catheter for structural and functional
      optical coherence tomography.
AB  - We describe a miniature fiber-optic Doppler imaging catheter for integrated
      functional and structural optical coherence tomography (OCT) imaging. The Doppler
      catheter can map blood flow within a vessel as well as image vessel wall
      structures. A prototype Doppler catheter has been developed and demonstrated for
      measuring the intraluminal velocity profile in a vessel phantom (conduit). A
      simple mathematical model is demonstrated to estimate the total flow rate. This
      estimation technique also enables the spatial range of flow measurements to be
      extended by approximately two times the normal OCT image-penetration depth. The
      Doppler OCT catheter could be a powerful device for cardiovascular imaging.

PMID- 18059734
TI  - Multimodal nonlinear spectral microscopy based on a femtosecond Cr:forsterite
      laser.
AB  - We demonstrate a novel multimodal nonlinear spectral microscopy based on a
      femtosecond Cr:forsterite laser at 1230 nm. By acquiring the whole nonlinear
      spectrum in the visible and near-NIR region, this novel technique allows a
      combination of different imaging modalities, including second-harmonic
      generation, third-harmonic generation, and multiple-photon fluorescence. Combined
      with the selected excitation wavelength, which is located in the IR transparency
      window, this microscopic technique can provide high penetration depth with
      reduced damage and is ideal for studying living cells.

PMID- 18059735
TI  - Three-dimensional hole drilling of silica glass from the rear surface with
      femtosecond laser pulses.
AB  - By moving silica glass in a preprogrammed structure, we directly produced three
      dimensional holes with femtosecond laser pulses in single step. When distilled
      water was introduced into a hole drilled from the rear surface of the glass, the
      effects of blocking and redeposition of ablated material were greatly reduced and
      the aspect ratio of the depth of the hole was increased. Straight holes of 4-mu;m
      diameter were more than 200 microm deep. Three-dimensional channels can be
      micromachined inside transparent materials by use of this method, as we have
      demonstrated by drilling a square-wave-shaped hole inside silica glass.

PMID- 18059736
TI  - Spectral phase and amplitude interferometry for direct electric-field
      reconstruction.
AB  - An extension of the well-known technique for spectral phase interferometry for
      direct electric-field reconstruction (SPIDER) has been developed that permits the
      reconstruction of the spectral amplitude and the spectral phase of ultrashort
      laser pulses from the acquisition of only one spectrum. Temporal intensity and
      temporal phase can therefore easily be retrieved. The characterization of pulses
      from a Ti:sapphire oscillator by use of an extended SPIDER is discussed.
      Advantages and drawbacks of the modified technique are also discussed.

PMID- 18059737
TI  - Quasi-optic terahertz imaging.
AB  - We demonstrate quasi-optical, diffraction-limited two-dimensional image
      production by means of reflected pulses of terahertz (THz) radiation. A spherical
      mirror is used to form a real one-to-one THz image of two 1-mm-diameter steel
      spheres, which is then scanned over a THz receiver. Diffraction-limited spatial
      (cross-range) resolution and THz pulse range resolution are simultaneously
      observed.

PMID- 18059738
TI  - Optical parametric amplification of a shaped white-light continuum.
AB  - Phase-locked two-color sub-40-fs double pulses in the visible are produced by
      noncollinear parametric amplification of white light tailored in a pulse shaper
      with a liquid-crystal mask. The carrier phase between the pulses is conserved
      during the amplification process and can be adjusted, as can the temporal
      separation and the center of wavelengths of the pulses.

PMID- 18059739
TI  - Directional emission from whispering-gallery modes in deformed fused-silica
      microspheres.
AB  - Highly directional emissions from whispering-gallery modes are demonstrated in
      deformed nonaxisymmetric fused-silica microspheres. Ray trajectory analysis
      indicates that ray dynamics in a three-dimensional reso-nator differs
      qualitatively from that of a two-dimensional system, with Arnol'd diffusion
      playing an essential role in the three-dimensional system.

PMID- 18059740
TI  - Tunable resonance fluorescence monochromator with sub-Doppler spectral
      resolution.
AB  - A cesium-based resonance fluorescence monochromator with a spectral resolution of
      200 MHz and a tunable response over the D(2) absorption line of cesium (380 MHz)
      is described. The narrow spectral response is achieved through excitation of a
      monokinetic population of the 6(2)P(3/2)( degrees ) state by arrangement of the
      excitation lasers in either a copropagating or a counterpropagating orientation.
      The narrow spectral response of the detector allows for excitation of specific
      hyperfine components involved in the 6(2)P(3/2)( degrees ) (F=3-5) to 6(2)D(5/2)
      (F=2-6) transition (917.23 nm). The selectivity gained through resolving specific
      hyperfine transitions allows for a photon detector that is both spectrally
      tunable and narrow. We report the sub-Doppler linewidths achieved through various
      laser beam orientations. We also describe how these beam geometries can be
      applied to spectrally narrow and tunable image detection.

PMID- 18059741
TI  - Simultaneous measurement of axial strain, temperature, and transverse load by a
      superstructure fiber grating.
AB  - A novel and simple fiber-optic sensor based on a superstructure fiber grating for
      simultaneous measurement of temperature, axial strain, and transverse load is
      proposed and demonstrated. By measurement of the shift and split of broadband and
      narrow-band loss peaks, one can determine the temperature, axial strain, and
      transverse load simultaneously over the ranges 0-140 degrees , 0-1200muepsilon,
      and 0-0.3 kg/mm, respectively.

PMID- 18059742
TI  - Blue amplified spontaneous emission from a stilbenoid-compound-doped polymer
      optical fiber.
AB  - We report on the fabrication and characteristics of a step-index glass-clad
      polymer optical fiber that uses a novel fluorescent stilbenoid compound for
      lasing and amplification applications. The compound, 1, 4-bis(4-diphenyl-amino
      styryl)-benzene, is specifically designed for the blue region of the spectrum and
      has a very high quantum yield of 0.85 in a solid-state polymer host and a large
      Stokes shift. Significant spectral narrowing and superlinear increase of output
      intensity are observed under photoexcitation at 355 nm, which are indicative of
      the occurrence of amplified spontaneous emission. By means of gain spectroscopy,
      a large optical gain of up to 36 cm(-1) at 494 nm has been obtained for the fiber
      when it is transversely photoexcited at 12 mJ/cm(2) . The waveguide loss has been
      measured to be 0.7 cm(-1) at 494 nm. The demonstration of high gain and low
      waveguide loss has favorable implications for the construction of a very compact,
      tunable coherent light source.

PMID- 18059743
TI  - Relaxation of the alignment tolerances of a 1.55-mum extended-cavity
      semiconductor laser by use of an intracavity photorefractive filter.
AB  - Commercial grating-tuned single-mode extended-cavity semiconductor lasers (ECLDs)
      can be tuned over 100 nm near 1.55mum . This continuous tuning with no mode
      hopping requires delicate factory adjustments and high mechanical stability so
      that the wavelength precision is kept as high as possible and the mismatch
      between the lasing wavelength and the wavelength of minimum loss remains as small
      as possible. The addition of a photorefractive crystal inside the cavity creates
      an adaptive spectral filter that decreases the loss of the lasing mode and thus
      enhances its stability. For what is to our knowledge the first time, we
      demonstrate the extension of the available wavelength-mismatch range without mode
      hopping by the addition of a CdTe photorefractive crystal inside the cavity of a
      single-mode grating-tuned ECLD.

PMID- 18059744
TI  - Spatial mode control of a diode-pumped Nd:YAG laser by an intracavity liquid
      crystal light valve.
AB  - We present a new beam-shaping technique with an intracavity optically addressed
      liquid-crystal spatial light modulator. The Nd:YAG resonator is able to deliver
      beams with various spatial profiles such as flat-topped super-Gaussian and square
      shaped beams.

PMID- 18059745
TI  - Efficient frequency doubling of a pulsed laser diode by use of a periodically
      poled KTP waveguide crystal with Bragg gratings.
AB  - Blue light with an average power of as much as 7.5 mW in picosecond pulses has
      been generated at 486, 488, and 491 nm from a frequency-doubled, nonresonant
      injection seeded, gain-switched InGaAs/GaAs diode laser by use of a periodically
      poled KTP waveguide crystal that incorporates a Bragg grating section.

PMID- 18059746
TI  - Reconstruction of absorber concentrations in a two-layer structure by use of
      multidistance time-resolved reflectance spectroscopy.
AB  - The characterization of a two-layer structure was investigated by use of time
      resolved reflectance over a wide spectral range. We exploited the nonlinear
      dependence of the measured spectra on the upper-and lower-layer properties to
      formulate an algorithm for the recovery of absorber concentrations in both
      layers. The method assumes that the spectral features of the key absorbers are
      known, but it does not rely on a priori knowledge of the layer thickness. Phantom
      tests confirmed the accuracy of the estimate of the absorber concentrations to
      within 10% for thickness values ranging from 0.3 to 1.2 cm. Multidistance
      absorption spectra from 610 to 1000 nm were obtained in vivo from the forearms of
      human subjects, allowing us to estimate the concentration of key tissue
      constituents in a two-layer approximation. Good agreement between the
      reconstructed spectra and the experimental data taken from two volunteers with
      opposite predominance of adipose and muscular tissues demonstrated the validity
      of this approach.

PMID- 18059747
TI  - Endoscopic optical coherence tomography based on a microelectromechanical mirror.
AB  - An endoscopic optical coherence tomography (OCT) system based on a
      microelectromechanical mirror to facilitate lateral light scanning is described.
      The front-view OCT scope, adapted to the instrument channel of a commercial
      endoscopic sheath, allows real-time cross-sectional imaging of living biological
      tissue via direct endoscopic visual guidance. The transverse and axial
      resolutions of the OCT scope are roughly 20 and 10.2mum, respectively. Cross
      sectional images of 500x1000 pixels covering an area of 2.9 mmx2.8 mm can be
      acquired at ~5 frames/s and with nearly 100-dB dynamic range. Applications in
      thickness measurement and bladder tissue imaging are demonstrated.

PMID- 18059748
TI  - High-resolution optical correlation imaging in a scattering medium.
AB  - An optical correlation setup is used to image transparent objects through
      scattering media, and 10-mum longitudinal and 2.5-mum transverse resolution are
      achieved. Spectral-bandwidth sampling of the light source is made possible by a
      tunable dye laser and leads to signal enhancement as a result of sampling
      interferogram filtering. An optical system allows observation of sample slices
      without the need for a translation stage.

PMID- 18059749
TI  - Enhanced light transmission through a single subwavelength aperture.
AB  - The optical transmission through a subwavelength aperture in a metal film is
      strongly enhanced when the incident light is resonant with surface plasmons at
      the corrugated metal surface surrounding the aperture. Conversely, the aperture
      acts as a novel probe of the surface plasmons, yielding useful insights for
      optimizing the transmission enhancement. For the optimal corrugation geometry, a
      set of concentric circular grooves, three times more light is transmitted through
      the central subwavelength aperture than directly impinges upon it. This effect is
      useful in the fabrication of near-field optical devices with extremely high
      optical throughput.

PMID- 18059750
TI  - Imaging of laser-induced reactions of individual defect nanoclusters.
AB  - The response of individual defect nanoclusters located in the bulk of a
      dielectric material following exposure to 355-nm, 3-ns high-power laser
      irradiation is investigated by use of microscopic fluorescence imaging.
      Experiments were carried out on KH(2)PO(4) crystals. We provide direct imaging of
      the reaction to an external stimulus of individual defect clusters and
      demonstrate a novel method of studying the dynamic behavior of bulk defects.

PMID- 18059751
TI  - Design of switching junctions for two-dimensional discrete soliton networks.
AB  - The performance of switching junctions in two-dimensional discrete-soliton
      networks is analyzed theoretically by coupled-mode theory. Our analysis can be
      used for the design of routing junctions with specified operational
      characteristics. Appropriately engineering the intersection site can further
      improve the switching efficiency of these junctions. Our analytical results are
      verified by numerical simulations.

PMID- 18059752
TI  - Transverse instability of strongly coupled dark-bright Manakov vector solitons.
AB  - We show, by performing linear stability analysis and direct numerical
      simulations, that dark-soliton transverse instability is significantly reduced in
      Kerr media by strong coupling to a bright soliton. High instability suppression
      can be achieved by use of large-amplitude bright solitons.

PMID- 18059754
TI  - High-performance readout and recording by a combination aperture.
AB  - A solid immersion lens combined with a conical dielectric tip exhibits good
      resolution and efficiency in reading and recording data marks on optical storage
      media. We demonstrate a combination aperture that produces ~200-nm full-width
      1/e(2) spot size and achieves 50% optical efficiency in an edge-scan experiment.
      A comparison of recording with the combination aperture, with an unmodified solid
      immersion lens, and with a far-field system is made.

PMID- 18059753
TI  - Second-harmonic generation from a first-order quasi-phase-matched GaAs/AlGaAs
      waveguide crystal.
AB  - We demonstrate, for the first time to our knowledge, the generation of second
      harmonic pulses by use of a novel methodology for achieving first-order quasi
      phase matching in a semiconductor waveguide crystal. This methodology is based on
      a periodic modulation of the susceptibility coefficient along the direction of
      light-beam propagation in which advantage is taken of the fact that
      chi((2))(GaAs)>chi((2))(Al(x)Ga(1-x)As) . Efficient second-harmonic generation at
      975 nm of a pump wavelength of 1950 nm has been demonstrated for a crystal with a
      nonuniform domain dimension (duty cycle, ~39/61).

PMID- 18059755
TI  - Optical implementation of orthogonal phase-code multiplexing.
AB  - We propose a new optical implementation of orthogonal phase-code multiplexing in
      which an arbitrary phase shift of theta or theta +pi is used in the reference
      beam instead of 0 or pi as in the conventional method. To compare the new and the
      conventional methods, we employ a 2-bit orthogonal phase code and store two
      binary-data images in a BaTiO(3) crystal with each method. We also employ
      numerical methods to simulate the 2-bit phase-code multiplexing and show that the
      signal-to-noise ratio in the restored images is improved by more than one order
      of magnitude in the new method in our experimental conditions.

PMID- 18059756
TI  - Formation of a planar optical waveguide by mega-electron-volt He+ and P+ ions
      implanted in a BiB(3)O(6) crystal.
AB  - What is believed to be the first planar optical waveguide was formed in
      BiB(3)O(6) (BIBO) crystal by 2.8-MeV He(+)-ion implantation with a dose of
      2x10(16)ions/cm (2) and 2.8-MeV P(+)-ion implantation with a dose of
      1x10(14)ions/cm (2) at room temperature. We observed 21 darks modes for the He(+)
      ion-implanted BIBO waveguides and four dark modes for the P(+)-ion-implanted
      waveguides. The refractive-index profile of the He(+)-implanted BIBO waveguide
      was analyzed. The data also suggest that the BIBO waveguides formed by MeV He(+)
      ion and P(+)-ion implantation differ in their developing mechanisms.

PMID- 18059757
TI  - Poincare vortices.
AB  - Traditional interferometric methods for measuring the vortex structure of complex
      wave fields suffer from many intrinsic problems and seldom yield results of any
      accuracy. Using the unique properties of what I call Poincare vortices, I develop
      a radically different method based on Stokes parameters that offers many
      practical advantages. The theory of this new method is discussed, and its unique
      capabilities are illustrated by reconstruction with high accuracy of the vortex
      structure of a simulated random field containing numerous vortices, including
      several closely spaced vortex pairs that would be difficult, if not impossible,
      to resolve by traditional means.

PMID- 18059758
TI  - High-energy self-starting femtosecond Cr(4+):Mg(2)SiO(4) oscillator operating at
      a low repetition rate.
AB  - We describe a self-starting high-power femtosecond laser based on the
      Cr(4+):Mg(2)SiO(4) crystal that produces 17-nJ pulses of 40-fs duration at 26.5
      MHz repetition rate. This low repetition rate is achieved by employment of a one
      to-one telescope in the cavity. The pulse energy is five times greater than with
      a short-resonator laser. To our knowledge, the laser produces the highest energy
      ever achieved from this type of laser directly from the resonator without cavity
      dumping or external amplification. We believe that this laser source can be used
      for many applications, including nonlinear optics, microscopic imaging, and
      micromachining of silicon and other semiconductor materials.

PMID- 18059759
TI  - Propagation of single-cycle terahertz pulses in random media.
AB  - We describe what are to our knowledge the first measurements of the propagation
      of coherent, single-cycle pulses of terahertz radiation in a scattering medium.
      By measuring the transmission as a function of the length L of the medium, we
      extract the scattering mean free path l(s)(omega) over a broad bandwidth. We
      observe variations in l(s) ranging over nearly 2 orders of magnitude and covering
      the entire thin sample regime from L/l(s)<<1 to L/l(s)~10 . We also observe
      scattering-induced dispersive effects, which can be attributed to the additional
      path traveled by photons scattered at small angles.

PMID- 18059760
TI  - Efficient intracavity generation of visible pulses in a femtosecond near-infrared
      optical parametric oscillator.
AB  - We have achieved efficient simultaneous intracavity doubling of the signal
      frequency and sum-frequency generation between the signal and the pump in a
      periodically poled LiNbO(3) femtosecond optical parametric oscillator pumped by a
      Ti:sapphire laser. The responsible mechanisms are second-, third-, and fourth
      order quasi-phase matching (QPM). An ~56% poling duty cycle permits efficient
      even-order QPM. Femtosecond pulses tunable in the visible were generated with a
      total efficiency of more than 8% for only 480-mW pump power at 80 MHz.
      Optimization of the poling duty cycle can improve the efficiency further.

PMID- 18059761
TI  - Time-domain differentiation of terahertz pulses.
AB  - We report on the time-domain differentiation of light waves by metallic
      transmission gratings. Time-resolved terahertz experiments show that the first
      time derivative of an arbitrary waveform can be achieved by use of gratings of
      subwavelength period. The results are in accord with classical diffraction theory
      and may permit novel applications for tailoring few-cycle light pulses and
      ultrahigh-frequency optoelectronics.

PMID- 18059762
TI  - Diffractive Alvarez lens.
AB  - A diffractive Alvarez lens is demonstrated that consists of two separate phase
      plates, each having complementary 16-level surface-relief profiles that contain
      cubic phase delays. Translation of these two components in the plane of the phase
      plates is shown to produce a variable astigmatic focus. Both spherical and
      cylindrical phase profiles are demonstrated with good accuracy, and the discrete
      surface-relief features are shown to cause less than lambda/10 wave-front
      aberration in the transmitted wave front over a 40 mm x 80 mm region.

PMID- 18059763
TI  - Characterization and imaging in optically scattering media by use of laser
      speckle and a variable-coherence source.
AB  - We demonstrate the application of laser-speckle statistics formed by a variable
      coherence source illuminating a scattering medium, for determining the scattering
      parameter mu;(s)>(?) of a diffusion model for the medium. Furthermore, we apply
      this technique to visualize laterally localized inhomogeneities embedded within a
      highly scattering sample.

PMID- 18059764
TI  - Frequency-domain technique for optical property measurements in moderately
      scattering media.
AB  - We demonstrate a reflection geometry frequency-domain technique that is suitable
      for measurement of the optical properties of a medium with moderate scatter and
      absorption (mu(s) and mu(a) ~ 1 m(-1)). Variations in absorption and scatter
      produce opposing tends in the amplitude signal and common trends in the phase
      signal, allowing unique determination of absorption and scattering coefficients
      for a given phase function. An analytical model based on single-scattering events
      gives good agreement with experimental measurements.

PMID- 18059765
TI  - Optical guidance of terrawatt laser pulses by the implosion phase of a fast Z
      pinch discharge in a gas-filled capillary.
AB  - A new method of optical guidance by the implosion phase of a fast Z-pinch
      discharge in a gas-filled capillary is proposed. An imploding plasma column has a
      concave electron-density profile in the radial direction, just before a
      stagnation phase driven by a converging current sheet and a shock wave. The
      feasibility of optical guidance of a high-intensity (>1 x 10(17) W/cm(2))
      Ti:sapphire laser pulse by use of this method over a distance of 2 cm,
      corresponding to 12.5 times the Rayleigh length, has been experimentally
      demonstrated. The guiding-channel formation process was directly probed with a He
      Ne laser beam. The electron density in the fully ionized channel was estimated to
      be 2.0 x 10(17) cm(-3) on the axis and 7.0 x 10(17) cm(-3) on the peaks of the
      channel edge, with a diameter of 70 mum, as indicated by the experimental
      results, which were corroborated by a magnetohydrodynamics simulation.

PMID- 18059766
TI  - Photoexcited GaAs surfaces studied by transient terahertz time-domain
      spectroscopy.
AB  - The transmission characteristics of an air-GaAs interface and the transient
      absorption and index spectra of the thin, photoexcited surface layer are
      investigated subsequent to excitation by a femtosecond laser pulse. We find that
      the total phase change and transmission of a terahertz (THz) probe pulse are
      dominated by interface effects. This observation has important implications in
      the interpretation of THz time-domain spectroscopy data of absorbing media. We
      also observe that the THz pulse apparently arrives at the detector as much as 60
      fs earlier when it is transmitted through an optically excited GaAs wafer. This
      effect is fully explained in terms of a frequency-dependent transmission and
      phase shift at the air-GaAs interface and is not associated with superluminal
      propagation.

PMID- 18059767
TI  - Determining the absolute carrier phase of a few-cycle laser pulse.
AB  - In a strong laser field, electrons tunnel from an atom at a rate determined by
      the instantaneous field. If the pulse is only a few cycles in duration, the
      highly nonlinear nature of tunnel ionization ensures that the resultant electron
      wave packet is primarily formed in less than one period. Measuring the direction
      of above-threshold-ionization electrons produced by circularly polarized light
      provides a direct method of measuring the absolute carrier phase of a single
      pulse. The method is robust, surviving spatial and temporal integration as well
      as intensity fluctuations.

PMID- 18059768
TI  - Jones matrix for second-order polarization mode dispersion.
AB  - A Jones matrix is constructed for a fiber that exhibits first- and second-order
      polarization mode dispersion (PMD). It permits the modeling of pulse transmission
      for fibers whose PMD vectors have been measured or whose statistics have been
      determined by established PMD theory. The central portion of our model is a
      correction to the Bruyere model.

PMID- 18059769
TI  - Spectral interference measurement of nonlinear pulse propagation dynamics in
      optical fibers.
AB  - Ultrafast pulse shaping and ultrafast pulse spectral phase-retrieval techniques
      are used in the spectral interference measurement of nonlinear pulse propagation
      dynamics in dispersion-shifted optical fiber. Nonlinear responses in both
      amplitude profile and phase profile of the pulses at zero-dispersion wavelength
      as well as at nonzero-dispersion wavelength are directly measured. A numerical
      simulation that uses a third-oder-dispersion-included nonlinear Schrodinger
      equation gives excellent agreement with the experimental data.

PMID- 18059770
TI  - Visible continuum generation in air-silica microstructure optical fibers with
      anomalous dispersion at 800 nm.
AB  - We demonstrate experimentally for what is to our knowledge the first time that
      air-silica microstructure optical fibers can exhibit anomalous dispersion at
      visible wavelengths. We exploit this feature to generate an optical continuum 550
      THz in width, extending from the violet to the infrared, by propagating pulses of
      100-fs duration and kilowatt peak powers through a microstructure fiber near the
      zero-dispersion wavelength.

PMID- 18059771
TI  - Securing information by use of digital holography.
AB  - An information security method that uses a digital holographic technique is
      presented. An encrypted image is stored as a digital hologram. The decryption key
      is also stored as a digital hologram. The encrypted image can be electrically
      decrypted by use of the digital hologram of the key. This security technique
      provides secure storage and data transmission. Experimental results are presented
      to demonstrate the proposed method.

PMID- 18059772
TI  - Method for designing arbitrary two-dimensional continuous phase elements.
AB  - We propose a method for designing arbitrary two-dimensional continuous phase
      elements. The phase anomalies that are due to amplitude zeros that occur in
      conventional design methods can be avoided completely with this method. Therefore
      the method is also useful for designing holographic elements that are free from
      amplitude zeros. The method is based on an iterative Fourier-transform algorithm.
      In the iteration process the method operates on the unwrapped phase.
      Consequently, a subsequent continuation step is not needed.

PMID- 18059773
TI  - Efficient, multiwatt, continuous-wave laser operation on the (4)F((3/2))
      (4)I((9/2)) transitions of Nd:YVO(4) and Nd:YAG.
AB  - We report multiwatt, diode-pumped cw operation on the (4)F(3/2)-(4)I(9/2) laser
      transition at 914.5 nm in Nd:YVO(4), for which an output power of 3.0 W and a
      slope of efficiency of 22.8% were achieved. For the corresponding laser
      transition of Nd:YAG at 946 nm an output power of 5.35 W and a slope efficiency
      of 40.2% were measured. By intracavity frequency doubling, an output power of 1.5
      W at 473 nm was generated.

PMID- 18059774
TI  - High-energy, high-power ytterbium-doped Q-switched fiber laser.
AB  - We report on a Q -switched, cladding-pumped, ytterbium-doped large-mode-area
      fiber laser operating at 1090 nm that is capable of generating 2.3 mJ of output
      pulse energy at a 500-Hz repetition rate and more than 5 W of average output
      power at higher repetition rates in a high-brightness beam (M(2) = 3) . Using a
      similar fiber with a smaller core, we generated >0.5-mJ pulses in a diffraction
      limited beam. Our results represent a threefold increase in pulse energy over
      previously published values for Q-switched fiber lasers and firmly establish
      fiber lasers as compact, multiwatt, multimillijoule pulse sources with large
      scope for both industrial and scientific applications.

PMID- 18059775
TI  - Analysis of pulse dropout in harmonically mode-locked fiber lasers by use of the
      Lyapunov method.
AB  - Using a stability analysis based on the Lyapunov method, we study pulse dropout
      in an actively mode-locked fiber laser. The analysis gives a limit on the maximum
      pulse duration and the minimum laser power that are needed for stable operation
      without pulse dropout. The stability of pulse trains was studied analytically and
      validated numerically for different pulse shapes.

PMID- 18059776
TI  - Diffusion coefficient in photon diffusion theory.
AB  - The choice of the diffusion coefficient to be used in photon diffusion theory has
      been a subject of discussion in recent publications on tissue optics. We compared
      several diffusion coefficients with the apparent diffusion coefficient from the
      more fundamental transport theory, D(app). Application to point sources in turbid
      media, for which exact solutions are available, showed that D(app) has to be
      preferred. We give a simple equation to approximate D(app) for several phase
      functions that apply to tissue optics. Reasons for the remaining discrepancies in
      diffusion coefficients applied to time-resolved and time-averaged descriptions of
      photon propagation in homogeneous turbid media are discussed.

PMID- 18059777
TI  - Lateral resolution enhancement with standing evanescent waves.
AB  - A high-resolution fluorescence microscopy technique has been developed that
      achieves a lateral resolution of better than one sixth of the emission wavelength
      (FWHM). By use of a total-internal-reflection geometry, standing evanescent waves
      are generated that spatially modulate the excitation of the sample. An enhanced
      two-dimensional image is formed from a weighted sum of images taken at different
      phases and directions of the standing wave. The performance of such a system is
      examined through theoretical calculations of both the point-spread function and
      the optical transfer function.

PMID- 18059778
TI  - Vacuum-cored hollow waveguide for transmission of high-energy, nanosecond Nd:YAG
      laser pulses and its application to biological tissue ablation.
AB  - A vacuum-cored hollow waveguide has been found to transmit 1064-nm, Q-switched
      Nd:YAG laser pulses. With this scheme, laser-induced air breakdown was completely
      suppressed, and the laser-induced damage threshold of the waveguide's inner
      coating was significantly increased. With a 1-m-long, 1-mm inner-diameter, cyclic
      olefin polymer-coated silver hollow waveguide, the maximum transmitted laser
      energy was as great as 158 mJ/pulse (20.1 J/cm(2)), at a repetition rate of 10 Hz
      in a 90 degrees -bent waveguide condition. The corresponding transmitted peak
      laser power was 17.6 MW. With the transmitted laser pulses, deep ablation of
      myocardium tissues was demonstrated in vitro.

PMID- 18059779
TI  - Smart microscope: an adaptive optics learning system for aberration correction in
      multiphoton confocal microscopy.
AB  - Off-axis aberrations in a beam-scanning multiphoton confocal microscope are
      corrected with a deformable mirror. The optimal mirror shape for each pixel is
      determined by a genetic learning algorithm, in which the second-harmonic or two
      photon fluorescence signal from a reference sample is maximized. The speed of the
      convergence is improved by use of a Zernike polynomial basis for the deformable
      mirror shape. This adaptive optical correction scheme is implemented in an all
      reflective system by use of extremely short (10-fs) optical pulses, and it is
      shown that the scanning area of an f:1 off-axis parabola can be increased by nine
      times with this technique.

PMID- 18059780
TI  - Waveguiding properties of optical vortex solitons.
AB  - An optical vortex soliton induces a graded-index waveguide over an extended
      propagation distance in a self-defocusing nonlinear optical medium. Using
      numerical techniques, we determine the waveguide dispersion and optimal size of
      the guided beam.

PMID- 18059782
TI  - Multicomponent two-dimensional solitons carrying topological charges.
AB  - We propose multihump N-component two-dimensional vector solitons for which each
      constituent carries a different topological charge. These new structures exhibit
      a unique triple-point phase diagram that is completely absent in the two
      component limit.

PMID- 18059781
TI  - 20-W ultraviolet-beam generation by fourth-harmonic generation of an all-solid
      state laser.
AB  - We have obtained UV power of 20.5 W with a repetition rate of 10 kHz by the use
      of a high-brightness high-power all-solid-state green laser and a high-quality
      CsLiB(6)O(10) crystal. This power is, to our knowledge, the highest UV power
      achieved so far in all-solid-state lasers.

PMID- 18059783
TI  - Graphic tool to produce tailored symmetrical phase-shifting algorithms.
AB  - We employ the Fourier-transform graphic representation of a set of
      antisymmetrical and symmetrical sampling reference harmonics to obtain new
      symmetrical phase-shifting algorithms tailored to specific characteristics. As an
      example, a new detuning-insensitive seven-point algorithm, with a third signal
      harmonic insensitivity and which is detuning insensitive at this frequency, is
      derived.

PMID- 18059784
TI  - 7.5-MHz data-transfer rate with a planar aperture mounted upon a near-field
      optical slider.
AB  - We fabricated a planar aperture-mounted (PAM) slider by use of a focused ion beam
      to demonstrate fast data acquisition for near-field optical data storage. The
      aperture (200 nm x 500 nm) was formed upon the Ti-coated air-bearing surface of
      the slider and was directly illuminated with a laser (lambda = 532 nm) beam spot
      by use of an objective lens (N.A., 0.55). The light transmitted through the
      aperture was modulated by a Ti-coated SiO(2) disk with 200- and 400-nm-wide line
      and-space (L&S) patterns engraved by electron-beam lithography. The optical
      throughput of the taperless aperture was greater than 0.02. By use of the PAM
      slider, 400- and 200-nm L&S signals were detected at linear velocities of 6 and 3
      m/s, respectively, corresponding to a data-transfer rate of 7.5 MHz.

PMID- 18059785
TI  - Ultrabroad-bandwidth electro-optic modulator based on a cascaded Bragg grating.
AB  - It is shown that the bandwidth of a traveling-wave electro-optical modulator can
      be greatly increased by matching of the group velocities of the optical and rf
      waves in the waveguides with cascaded Bragg gratings. A LiNbO>(3) Mach-Zehnder
      modulator with 1-V half-wave voltage and a bandwidth in excess of 100 GHz is
      proposed and its performance evaluated.

PMID- 18059786
TI  - Pedestal antiresonant reflecting waveguides for robust coupling to microsphere
      resonators and for microphotonic circuits.
AB  - Strip-line pedestal antiresonant reflecting waveguides are high-confinement,
      silica integrated optical waveguides in which the optical modes are completely
      isolated from the substrate by thin high-index layers. These waveguides are
      particularly well suited for whispering-gallery mode excitation in high-Q
      microspheres. They can also be used in microphotonic circuits, such as for
      microring resonators. The theory and design of these structures are highlighted.
      Experiments that show high coupling efficiency to microspheres are also
      demonstrated.

PMID- 18059787
TI  - Quantum limits in the measurement of very small displacements in optical images.
AB  - We consider the problem of the measurement of very small displacements in the
      transverse plane of an optical image with a split photodetector. We show that the
      standard quantum limit for such a measurement, which is equal to the diffraction
      limit divided by the square root of the number of photons used in the
      measurement, cannot be overcome by use of ordinary single-mode squeezed light. We
      give the form of possible multimode nonclassical states of light, enabling us to
      enhance by orders of magnitude the resolution of such a measurement beyond the
      standard quantum limit.

PMID- 18059788
TI  - Comment on "Interference of traveling nondiffracting beams".

PMID- 18059789
TI  - Reply to comment on "Interference of traveling nondiffracting beams".

PMID- 18059790
TI  - Spatial-spectral holographic correlator at 1536 nm using 30-symbol quadriphase-
      and binary-phase-shift keyed codes.
AB  - Optical 30-symbol quadriphase-shift keyed (QPSK) and binary-phase-shift keyed
      (BPSK) codes were processed in a spatial-spectral holographic correlator with the
      Er(3+): Y(2)SiO(5) spectral hole-burning material operating at 1536 nm in the
      important 1550-nm communications band. The results demonstrate the ability of
      spatial-spectral holographic correlators to process QPSK codes and BPSK codes
      with the same apparatus. The high-fidelity correlations produced by this optical
      coherent transient device exhibit the low sidelobe characteristics expected for
      the codes used.

PMID- 18059791
TI  - Fabrication of long-period optical fiber gratings by use of ion implantation.
AB  - We report the fabrication of long-period optical fiber gratings by use of a
      refractive-index increase induced by ion implantation. Helium ions were implanted
      in an optical fiber core through a metal mask that had a 170-microm -pitch
      grating with spacing of 60 microm . We obtained a wavelength-dependent effective
      transmission loss by use of the grating.

PMID- 18059792
TI  - Distributed Bragg grating sensing with a direct group-delay measurement
      technique.
AB  - A new method of distributed in-fiber Bragg grating sensing is proposed. A method
      is outlined by which the strain field imposed upon a Bragg grating sensor is
      obtained by measurement of the sensor's reflectivity and delay characteristics.
      The proposal is demonstrated by interrogation of two loaded samples. Strain
      distributions from these experiments are compared against a theoretical estimate.
      The data treatment is also discussed. Strain resolution is found to be +/-24
      microepsilon, with a spatial resolution defined by a minimum spatial wavelength
      component of the coupling distribution of 1.65 mm.

PMID- 18059793
TI  - Disintegration of a soliton in a dispersion-managed optical communication line
      with random parameters.
AB  - The propagation of dispersion-managed solitons in optical fiber links with a
      random dispersion map has been studied. Two types of randomness are
      considered:random dispersion magnitudes and random lengths of the spans. By
      numerical simulations, disintegration of a soliton propagating in such an optical
      communication line is shown to occur. It is observed that the stability of the
      soliton propagation is affected more by modulations of the dispersion magnitudes
      of the spans than by modulations of the span lengths. Results of numerical
      simulations of the soliton breakup distance confirm theoretical predictions in
      the averaged dynamics limit.

PMID- 18059794
TI  - Analysis of air-guiding photonic bandgap fibers.
AB  - We present what is to our knowledge the first theoretical analysis of air-guiding
      photonic bandgap fibers. The fibers are characterized by a large hollow core and
      a microstructured cladding exhibiting photonic bandgap effects. Using an
      efficient, full-vectorial numerical method, we explain the operational principle
      of the fibers and obtain detailed information about the properties of the air
      guided modes. This information includes accurate determination of the modes'
      spectral extent, cutoff properties, and mode-field distributions.

PMID- 18059795
TI  - Image processing with the radial Hilbert transform: theory and experiments.
AB  - The Hilbert transform is useful for image processing because it can select which
      edges of an input image are enhanced and to what degree the edge enhancement
      occurs. However, the transform operation is one dimensional and is not applicable
      for arbitrarily shaped two-dimensional objects. We introduce a radially symmetric
      Hilbert transform that permits two-dimensional edge enhancement. We implement one
      dimensional, two-dimensional, and radial Hilbert transforms with a programmable
      phase-only liquid-crystal spatial light modulator. Experimental results are
      presented.

PMID- 18059796
TI  - Video-rate optical low-coherence reflectometry based on a linear smart detector
      array.
AB  - A low-coherence reflectometer based on a conventional Michelson interferometer
      and a novel silicon detector chip that allows parallel heterodyne detection is
      presented. Cross-sectional images of 64x256 pixels covering an area of 1.92 mm x
      1.3 mm are acquired at video rate and with a sensitivity close to the shot-noise
      limit. Applications in surface profiling and thickness measurement are
      demonstrated.

PMID- 18059797
TI  - High-brightness 138-W green laser based on an intracavity-frequency-doubled diode
      side-pumped Q-switched Nd:YAG laser.
AB  - Green power of 138 W was generated at an estimated beam quality of M(2) = 11 by
      intracavity frequency doubling of a diode-pumped Nd:YAG laser. The laser employs
      a diffusive close-coupled diode-pumping design and a bifocusing-compensation
      resonator design to ensure stable operation.

PMID- 18059798
TI  - Semiconductor laser with curved deep-etched distributed Bragg reflectors
      supporting a planar Gaussian mode.
AB  - A compact integration-compatible semiconductor laser supporting a planar Gaussian
      mode is demonstrated. Curved deep-etched distributed Bragg reflectors (DBR's),
      contouring the phase front of the Gaussian wave, act as feedback elements. The
      DBR's are 0.5 microm deep and have two first-order air gaps separated by a third
      order semiconductor spacer. Low-threshold current (10 mA) is achieved for a 90
      microm-long laser with a waist of 2 microm. Lasing in a planar Gaussian mode is
      observed up to 1.7 times the threshold current, whereas at higher currents the
      mode behavior degrades because of spatial hole burning.

PMID- 18059799
TI  - Spectroscopic optical coherence tomography.
AB  - Spectroscopic optical coherence tomography (OCT), an extension of conventional
      OCT, is demonstrated for performing cross-sectional tomographic and spectroscopic
      imaging. Information on the spectral content of backscattered light is obtained
      by detection and processing of the interferometric OCT signal. This method allows
      the spectrum of backscattered light to be measured over the entire available
      optical bandwidth simultaneously in a single measurement. Specific spectral
      features can be extracted by use of digital signal processing without changing
      the measurement apparatus. An ultrabroadband femtosecond Ti:Al(2)O(3) laser was
      used to achieve spectroscopic imaging over the wavelength range from 650 to 1000
      nm in a simple model as well as in vivo in the Xenopus laevis (African frog)
      tadpole. Multidimensional spectroscopic data are displayed by use of a novel hue
      saturation false-color mapping.

PMID- 18059800
TI  - Phase-resolved optical coherence tomography and optical Doppler tomography for
      imaging blood flow in human skin with fast scanning speed and high velocity
      sensitivity.
AB  - We have developed a novel phase-resolved optical coherence tomography (OCT) and
      optical Doppler tomography (ODT) system that uses phase information derived from
      a Hilbert transformation to image blood flow in human skin with fast scanning
      speed and high velocity sensitivity. Using the phase change between sequential
      scans to construct flow-velocity imaging, this technique decouples spatial
      resolution and velocity sensitivity in flow images and increases imaging speed by
      more than 2 orders of magnitude without compromising spatial resolution or
      velocity sensitivity. The minimum flow velocity that can be detected with an
      axial-line scanning speed of 400 Hz and an average phase change over eight
      sequential scans is as low as 10 microm/s, while a spatial resolution of 10
      microm is maintained. Using this technique, we present what are to our knowledge
      the first phase-resolved OCT/ODT images of blood flow in human skin.

PMID- 18059801
TI  - Third-harmonic generation by cascading second-order nonlinear processes in a
      cerium-doped KTiOPO4 crystal.
AB  - We have achieved effective third-harmonic generation (THG) by cascading second
      harmonic and sum-frequency generation in a single cerium-doped KTiOPO (4) crystal
      by using femtosecond laser pulses at 1.32 microm. A conversion efficiency of
      0.17% was achieved with an average pump power of 35 mW.Furthermore, a unique
      quadratic power dependence for this type of THG was confirmed. We developed a
      theory and obtained an analytical solution for the THG.The solution exactly
      describes the measured characteristics of the THG.

PMID- 18059802
TI  - Effect of counterintuitive time delays in nonlinear mixing.
AB  - The effect of varying the relative arrival time of the two laser pulses employed
      in doubly resonant four-wave sum mixing, enhanced by induced transparency, is
      studied with the aim of optimizing the efficiency of vacuum-ultraviolet
      generation. With atomic hydrogen as the nonlinear medium, pulsed radiation with
      wavelengths of 243 and 656 nm and durations of 8 and 14 ns, respectively, is
      mixed to generate 103-nm coherent radiation. It is shown that by delaying the
      arrival time of the ground-state pump beam (243 nm) by 2.5-3.5 ns relative to the
      arrival of the upper-state coupling beam (656 nm), it is possible to enhance the
      generated intensity by a factor of 2 or more.

PMID- 18059803
TI  - Vortex-stripe soliton interactions.
AB  - We study the interaction of an optical vortex soliton with a dark-soliton stripe
      in a bulk nonlinear defocusing medium. We develop a multiscale asymptotic theory
      to predict the main effect of the interaction and then study it experimentally,
      observing vortex-induced stripe bending, development of the transverse
      instability, and stripe breakup.

PMID- 18059804
TI  - Observed rotational enhancement of nonlinear optical vortices.
AB  - The propagation dynamics of an optical vortex pair is experimentally confirmed to
      experience enhanced rotation in a self-defocusing medium. We measured this effect
      to be 3.5 times larger than in linear media. The enhancement is attributed to
      nonlinear refraction within the dark vortex cores, permitting the vortices to
      propagate as vortex filaments.

PMID- 18059806
TI  - Time reversal of ultrafast waveforms by wave mixing of spectrally decomposed
      waves.
AB  - Two different realizations of time-reversal experiments of ultrafast waveforms
      are carried out in real time by use of four-wave mixing arrangements of
      spectrally decomposed waves. The first, conventional, method is based on phase
      conjugation of the waveform's spectrum and achieves time reversal of real
      amplitude waveforms. The second arrangement of the spectrally decomposed waves
      spatially inverts the waveform's spectrum with respect to the optical axis of the
      processor and achieves true time reversal for complex-amplitude ultrafast
      waveforms. We compare and contrast these two real-time techniques.

PMID- 18059805
TI  - Enhancement of ultraviolet photorefraction in highly magnesium-doped lithium
      niobate crystals.
AB  - We investigate UV photorefraction in Mg-doped LiNbO(3) crystals. Strong UV
      photorefraction is achieved in highly Mg-doped LiNbO(3) crystals with high two
      wave mixing gain, fast response, and low noise. It is also demonstrated
      experimentally that so-called damage-resistant dopants such as Mg are damage
      resistant only in the visible and that they will enhance photorefraction in the
      UV.

PMID- 18059807
TI  - Extreme ultraviolet interferometry measurements with high-order harmonics.
AB  - We demonstrate that high-order harmonics generated by short, intense laser pulses
      in gases provide an interesting radiation source for extreme ultraviolet
      interferometry, since they are tunable, coherent, of short pulse duration, and
      simple to manipulate. Harmonics from the 9th to the 15th are used to measure the
      thickness of an aluminum layer. The 11th harmonic is used to determine the
      spatial distribution of the electron density of a plasma produced by a 300-ps
      laser. Electronic densities higher than 2-10(20)electrons/cm>(3) are measured.

PMID- 18059808
TI  - Full-field characterization of femtosecond pulses by spectrum and cross
      correlation measurements: addenda.

PMID- 18059809
TI  - Partially coherent conical beams.
AB  - We introduce a new class of partially coherent beams that can propagate over
      large distances without changing their transverse profiles and their coherence
      properties. Such beams are generated by an incoherent superposition of identical
      fully coherent beams of arbitrary form, whose axes lie on a cone.

PMID- 18059810
TI  - Role of adjacent-pulse overlap in the interaction between dispersion-managed
      solitons.
AB  - Periodic breathing of pulse width owing to strong dispersion management leads to
      significant overlap between adjacent pulses in long-distance fiber-optic
      transmissions. A striking result is that beyond a critical degree of overlap the
      interaction forces are no longer increased and are even reduced as the overlap is
      enhanced.

PMID- 18059811
TI  - All-optical noise-subtraction scheme for a fiber-optic gyroscope.
AB  - A new intensity-noise-subtraction scheme for an interferometric fiber-optic
      gyroscope is demonstrated. Together with the light circulating through the gyro
      coil, an appropriately attenuated light beam from the source coupler dead end of
      the gyro is directed to the gyro photodetector. When the gyro is unmodulated, or
      modulated with a square wave at the proper frequency, the intensity noises of the
      two beams bear opposite phases and interfere destructively on the detector. For
      an unmodulated gyro, we demonstrate an intensity noise-reduction factor of ~35,
      and for the same gyro modulated with a square wave at the proper frequency, we
      demonstrate a reduction factor of ~15.

PMID- 18059812
TI  - Flexible small-bore hollow fibers with an inner polymer coating.
AB  - Flexible hollow-glass fibers with small-bore diameters of 250 and 320 mum have
      been developed for Er:YAG laser delivery. The fibers consist of a glass capillary
      tube and an inner coating of silver and polymer thin films that are deposited by
      use of a simple liquid-phase technique. The 250-mum-bore fiber exhibits a
      straight loss of 0.8 dB/m and a bending loss of 1.2 dB when it is bent 180
      degrees at the output end, with a bending radius of 2 cm. The maximum energy
      delivered by the fibers is ~100 mJ.

PMID- 18059813
TI  - Dispersion management in a harmonically mode-locked fiber soliton laser.
AB  - Harmonically mode-locked Er-fiber soliton lasers have become a reliable source of
      high-repetition-rate picosecond pulses in high-speed communications and photonic
      analog-to-digital conversion systems because of their low-noise, dropout-free
      operation. We have fabricated such a laser with a strongly dispersion-managed
      cavity and modeled its operation, and we have found that dispersion management
      significantly extends the power range over which uninterrupted single-pulse
      production is attained and dramatically decreases the effects of amplified
      spontaneous emission on the phase noise of the laser.

PMID- 18059814
TI  - Transient response in high-resolution Brillouin-based distributed sensing using
      probe pulses shorter than the acoustic relaxation time.
AB  - We perform numerical simulations on a model describing a Brillouin-based
      temperature and strain sensor, testing its response when it is probed with
      relatively short pulses. Experimental results were recently published [e.g., Opt.
      Lett. 24, 510 (1999)] that showed a broadening of the Brillouin loss curve when
      the probe pulse duration is reduced, followed by a sudden and rather surprising
      reduction of the linewidth when the pulse duration gets shorter than the acoustic
      relaxation time. Our study reveals the processes responsible for this behavior.
      We give a clear physical insight into the problem, allowing us to define the best
      experimental conditions required for one to take the advantage of this effect.

PMID- 18059815
TI  - Stable multisoliton pulses in dispersion management with fiber Bragg gratings.
AB  - We have studied the propagation of prechirped Gaussian pulse pairs in a fiber
      Bragg grating dispersion-managed system. We discovered that, under quite general
      conditions, a number of individual pulses evolve to a stable bound multisoliton
      solution, with fixed values for the phase difference and the distance between
      adjacent pulses. These stable multisoliton solutions may propagate for long
      distances without deformation, with the ultimate distance limitation imposed by
      the noise amplification.

PMID- 18059816
TI  - Localized holographic recording in doubly doped lithium niobate.
AB  - Persistent holograms are recorded locally with red light in a LiNbO>(3) crystal
      doped with Mg and Fe. Selective erasure is realized by use of a focused UV
      sensitizing light. We demonstrate the recording of 50 localized images as well as
      selective erasure in a 4 mm x 4 mm x 4 mm crystal. A comparison of the total
      recording time for M holograms obtained with the conventional distributed-volume
      recording and the localized methods is presented.

PMID- 18059817
TI  - Laser phase noise to intensity noise conversion by lowest-order group-velocity
      dispersion in optical fiber: exact theory.
AB  - An exact result for the spectral density of intensity variations that occur after
      propagation of ergodic light in a medium having lowest-order-only group-velocity
      dispersion is obtained and applied to the problem of semiconductor laser phase
      noise to intensity noise conversion in a single-mode optical fiber. It is shown
      that the intensity spectrum after propagation formally approaches, for a large
      laser linewidth or a long (or high-dispersion) fiber, the intensity spectrum of a
      thermal source having the same line shape as the laser.

PMID- 18059818
TI  - Mode-locked Cr(2+):ZnSe laser.
AB  - We describe active mode locking of a Cr(2+):ZnSe laser operating near 2.5 mum.
      The laser produces 4.4-ps transform-limited Gaussian-shaped pulses and produces
      82 mW of average power.

PMID- 18059819
TI  - Multipole analysis of the radiation from near-field optical probes.
AB  - We experimentally and theoretically analyze the radiation emitted from
      subwavelength-sized apertures in near-field optical probes. By decomposing the
      experimentally obtained radiation patterns into vector spherical waves, we
      describe the fields in terms of a series of multipole sources. We fit
      polarization-resolved angular intensity distributions, measured as far as 150
      degrees from the normal, with dipole, quadrupole, and octupole radiation. We find
      that the magnetic and the electric dipole components are dominant but that the
      interference terms between dipoles and higher-order poles are not negligible.
      This result can be used as the basis for understanding near-field optical
      interactions and images.

PMID- 18059820
TI  - High-power optical parametric oscillation in large-aperture periodically poled
      KTiOPO(4).
AB  - Electric field poling has been employed to fabricate 3-mm-thick periodically
      poled KTiOPO>(4) crystal for a high-power optical parametric oscillator. The
      maximum output power of the singly resonant optical parametric oscillator reached
      13 mJ with 45% efficiency when the resonator was pumped with a 2.2-mm-diameter
      beam from a Q-switched Nd:YAG laser. The influence of the cavity design on the
      spectral and spatial qualities of the output parametric radiation is also
      discussed.

PMID- 18059821
TI  - Raman gain measurement in solid parahydrogen.
AB  - We report a steady-state Raman gain measurement of the Q(1)(0) transition (v = 1
      ? 0, J = 0 ? 0) in solid parahydrogen. We carry out measurements by pumping with
      a continuous-wave frequency-doubled YAG laser at 532 nm and observing the direct
      amplification of a probe-laser beam for the first Stokes transition at 683 nm. A
      large single-pass amplification coefficient of 2.3 +/- 0.2 is obtained at a pump
      intensity of 46 kW/cm(2), with an interaction length of 1 cm, giving a steady
      state Raman gain coefficient of 18 +/- 3 cm/MW.

PMID- 18059822
TI  - 20-50-fs pulses tunable across the near infrared from a blue-pumped noncollinear
      parametric amplifier.
AB  - A two-stage blue-pumped noncollinearly phase matched optical parametric amplifier
      was used to generate near-infrared pulses that were continuously tunable from 865
      to 1600 nm. The pulse lengths scaled from 20 fs at the shorter wavelengths to
      below 50 fs at 1600 nm, with a nearly Fourier-transform-limited bandwidth. From
      200 muJ of 775-nm pump light at a 1-kHz repetition rate and a 130-fs duration, 7
      2.5-muJ pulse energies were generated, corresponding to a typical quantum
      efficiency of 25% from blue to near-infrared light.

PMID- 18059823
TI  - Generation of intense ultrabroadband optical pulses by induced phase modulation
      in an argon-filled single-mode hollow waveguide.
AB  - We experimentally demonstrate the generation of intense ultrabroadband optical
      pulses whose spectrum ranges from 300 to 1000 nm (700-THz bandwidth) with a well
      behaved spectral phase and 23-muJ pulse energy by a novel, simple setup utilizing
      induced phase modulation (IPM) in an argon-filled single-mode hollow waveguide.
      Fundamental as well as second-harmonic pulses produced by one common femtosecond
      pulse from a Ti:sapphire laser-amplifier system are copropagated in the hollow
      waveguide. The effect of the delay time between the two input pulses on the IPM
      spectral broadening is clarified and confirmed to agree with the theoretical
      result. It is found that the compressed pulse duration from this pulse is 1.51 fs
      if its phase is completely compensated for.

PMID- 18059824
TI  - Optical frequency measurement across a 104-THz gap with a femtosecond laser
      frequency comb.
AB  - The frequency-domain mode comb of a Ti:sapphire femtosecond laser centered at 350
      THz is broadened to 150 THz (full width at -30 dBc) by self-phase modulation in a
      single-mode optical fiber. By phase locking continuous-wave lasers to elements of
      the comb near 1064 and 778 nm, we measure the 104-THz frequency gap between these
      two lasers with a relative uncertainty of 2.7 x 10(-11) in 1 s.

PMID- 18059825
TI  - Generation of a beam with a dark focus surrounded by regions of higher intensity:
      the optical bottle beam.
AB  - A computer-generated hologram is used to form an optical beam with a localized
      intensity null at its focus. The beam is a superposition of two Laguerre-Gaussian
      modes that are phased so that they interfere destructively to give a beam focus
      that is surrounded in all directions by regions of higher intensity. Beams of
      this kind will have applications in the optical trapping of macroscopic objects
      or atoms; hence the term optical bottle beam.

PMID- 18059826
TI  - Enhanced diffraction efficiency of gratings in multilayers.
AB  - Computations with the rigorous differential method show that single gratings made
      by ion implantation have a diffraction efficiency in the +1 transmitted order
      under TE illumination of only 0.78%. The insertion of such gratings into
      multilayer dielectric Fabry-Perot cavities leads to an enhancement of the free
      space diffraction efficiency. Different designs for the multilayer are
      considered. An 18.8% efficiency is reached with 11-layer mirrors. This result is
      obtained by optimization of the thickness of the spacer of the Fabry-Perot cavity
      that contains the grating and centering of the wavelength of the mirrors. The
      dependence of optical properties of the structure on the various optogeometrical
      parameters of the structure is discussed.

PMID- 18059827
TI  - Optical carrier-suppression technique with a Brillouin-erbium fiber laser.
AB  - We demonstrate a new concept in optical carrier control that uses a simple
      arrangement based on a hybrid Brillouin-erbium fiber laser. The system offers
      precise tunable control of the optical carrier amplitude independently of the
      characteristics of the transmitter or the optical modulation format. As much as
      55 dB of carrier attenuation is demonstrated, which to our knowledge is the
      highest reported attenuation for a carrier-suppression system.

PMID- 18059828
TI  - Carbon dioxide laser-assisted poling of silicate-based optical fibers.
AB  - A novel poling method, carbon dioxide laser-assisted poling (CLAP), is
      demonstrated. Localized heating during CLAP is achieved through silicate
      absorption of the CO>(2) laser radiation. Electro-optic coefficients of 0.2 pm/V
      are achieved within a 55-s scan of a twin-hole fiber. It is shown that there is a
      range of CO>(2) laser powers for which the residual electro-optic coefficient is
      maximized.

PMID- 18059829
TI  - Long-period fiber gratings with variable coupling for real-time sensing
      applications.
AB  - We demonstrate a long-period grating whose resonance varies in strength but
      remains fixed in wavelength with either temperature or strain. Using this fiber
      grating sensor, we resolved a change of 1 muepsilon of strain or 0.04 degrees C
      in temperature. Such sensors require no spectrometer or other frequency-selective
      components and can operate in real time.

PMID- 18059831
TI  - Superresolution in far-field imaging.
AB  - Based on the idea of the complex filters suggested by Toraldo di Francia in 1952
      [Nuovo Cimento Suppl. 9, 426 (1952)], superresolved imaging has been achieved by
      use of interferometric image multiplication. A resolution limit of 55% of the
      Sparrow limit was achieved for incoherent objects.

PMID- 18059830
TI  - Holey fibers with random cladding distributions.
AB  - We provide what is to our knowledge the first direct confirmation that light can
      be guided in a holey fiber with randomly distributed air holes in the cladding.
      We also show that many of the features previously attributed to periodic holey
      fibers, in particular, single-mode guidance at all wavelengths, can also be
      obtained with random holey fibers. We provide insight into exactly how sensitive
      a holey fiber's optical properties are to the details of the cladding profile.

PMID- 18059832
TI  - Imaging through scattering media with depth resolution by use of low-coherence
      gating in spatiotemporal digital holography.
AB  - We demonstrate optical gating through scattering media based on low-coherence
      spatiotemporal digital holography. The method combines the advantages of low
      coherence gating, both temporal and spatial, with the advantages of methods using
      heterodyning and phase-sensitive detection. Spatiotemporal data are captured on a
      CCD detector in a single exposure, without mechanical scans, and processed
      digitally. Examples of reconstructions and sectioning of objects hidden behind a
      ground-glass diffuser are shown.

PMID- 18059834
TI  - Sampled-speckle photography for measurement of deformation.
AB  - Speckles usually are of two kinds: laser speckle and white-light speckle. An
      additional kind, termed a sampled speckle, is proposed. Whereas laser speckles
      arise from multiple interference of light scattered from an object illuminated by
      a coherent laser beam and white-light speckles are a physically generated speckle
      pattern on the surface of the object, sampled speckles are generated as a result
      of the sampling of a digital image. The generation of these speckles and their
      application to displacement measurement are demonstrated.

PMID- 18059833
TI  - Twin-image elimination experiments for three-dimensional images in optical
      scanning holography.
AB  - Twin-image elimination in the context of optical scanning holography has recently
      been proposed. The proposed technique involves simultaneously acquiring sine and
      cosine Fresnel holograms. A complex hologram is then formed by complex addition
      of the holograms, and twin-image rejection is predicted by computer simulations.
      An experimental verification of the technique by optical acquisition of the two
      holograms and subsequent reconstruction of the complex hologram digitally is
      reported. Three-dimensional image reconstruction without twin-image noise is
      demonstrated.

PMID- 18059835
TI  - Synthetic-aperture radar autofocus by maximizing sharpness.
AB  - To focus a synthetic-aperture radar image that is suffering from phase errors, a
      phase-error estimate is found that, when it is applied, maximizes the sharpness
      of the image. Closed-form expressions are derived for the gradients of a
      sharpness metric with respect to phase-error parameters, including both a point
      by-point (nonparametric) phase function and coefficients of a polynomial
      expansion. Use of these expressions allows for a highly efficient gradient-search
      algorithm for high-order phase errors. The effectiveness of the algorithm is
      demonstrated with an example.

PMID- 18059836
TI  - Laser-induced thermal-acoustic velocimetry with heterodyne detection.
AB  - Laser-induced thermal acoustics (LITA) was used with heterodyne detection to
      measure simultaneously and in a single laser pulse the sound speed and flow
      velocity of NO>(2) -seeded air in a low-speed wind tunnel up to Mach number M
      =0.1 . The uncertainties of the velocity and the sound speed measurements were
      ~0.2 m/s and 0.5%, respectively. Measurements were obtained through a nonlinear
      least-squares fit to a general, analytic closed-form solution for heterodyne
      detected LITA signals from thermal gratings. Agreement between theory and
      experiment is exceptionally good.

PMID- 18059837
TI  - Optical low-coherence reflectometer for differential phase measurement.
AB  - A birefringent-fiber-based dual-channel optical low-coherence reflectometer
      capable of differential phase measurement is described. Phase noise owing to
      environmental perturbations that is common to both channels is canceled,
      resulting in accurate measurement of the phase difference between light
      backscattered from two spatially separated sites. Results are presented that
      demonstrate the accuracy and sensitivity of the system.

PMID- 18059838
TI  - High-power, continuous-wave, current-tunable, single-mode quantum-cascade
      distributed-feedback lasers at lambda - 5.2 and lambda - 7.95 mum.
AB  - Quantum-cascade distributed-feedback lasers with high-power, continuous-wave
      (cw), tunable, single-mode emission are reported. The emission wavelengths are
      near 5.2 and 7.95 mum. The lasers are operated at liquid-nitrogen temperature and
      above. A maximum output power of >100 mW is obtained per facet at 80 K for both
      wavelengths, which is the result of careful positioning of the peak gain with
      respect to the Bragg wavelength. Continuous tuning with either heat-sink
      temperature or cw current is demonstrated. The tuning coefficients are 0.35 nm/K
      (5.2 mum) and 0.51 nm/K(7.95 mum) for thermal tuning and vary from 20 to 40 nm/A
      for tuning with current. The lasers are being used in high-resolution and high
      sensitivity gas-sensing applications.

PMID- 18059839
TI  - Engineering large anisotropy in amorphous glass.
AB  - By exploiting the strain-related rollover thresholds that occur between UV
      induced positive and negative index regimes in germanosilica glass it is possible
      to engineer large anisotropy into the structure. This is qualitatively analyzed
      for a planar waveguide and has been confirmed experimentally. However, the
      technique described here is not confined to waveguide devices and can in
      principle be applied to any glass structure that is capable of undergoing strain
      sensitive transitions.

PMID- 18059840
TI  - Phase plates for wave-aberration compensation in the human eye.
AB  - We present a method for manufacturing phase plates to compensate for the wave
      aberration in the human eye. The wave aberration of the eye is measured in vivo
      by a new laser ray-tracing method and then compensated for by a phase plate
      placed in front of the eye. This plate is made from a gray-level single-mask
      photosculpture in photoresist. Two experiments were carried out, first with an
      artificial eye and then with a human eye: 80% compensation for the wave
      aberration was achieved in both cases.

PMID- 18059841
TI  - Polarized light propagation through tissue phantoms containing densely packed
      scatterers.
AB  - We demonstrate that polarized light is maintained differently in densely packed
      versus dilute suspensions of polystyrene microspheres. The degrees of linear and
      circular polarization were measured versus scatterer concentration in aqueous
      suspensions of 0.48-, 0.99-, 2.092-, and 9.14-mum-diameter polystyrene
      microspheres. The results indicate that, for dilute suspensions of microspheres
      where independent scattering is assumed, the degrees of linear and circular
      polarization decrease as the scatterer concentration increases. For dense
      suspensions, however, the degree of polarization begins to increase as the
      scatterer concentration increases. The preferential propagation of linear over
      circular polarization states in dense suspensions is similar to results seen in
      biological tissue.

PMID- 18059842
TI  - Time-domain transillumination of biological tissues with terahertz pulses.
AB  - We present time-domain transmission imaging of an opaque structure in pork-fat
      tissue obtained with a terahertz (THz) field sampling technique. Compared with
      imaging with near-infrared pulses, the terahertz sampling technique shows
      significantly enhanced contrast, as a result of low scattering. For enhanced
      spatial resolution, we show mid-infrared THz imaging of onion cells. Water
      absorption of THz pulse in muscle tissues is discussed.

PMID- 18059843
TI  - Optimized pupil-plane filters for confocal microscope point-spread function
      engineering.
AB  - We present a new method of superresolving pupil-plane filter design in confocal
      microscopy in which we specify the properties of the desired point-spread
      function and use an optimization procedure to determine a suitable pupil-plane
      filter. A new, flexible method of filter implementation using reconfigurable
      binary optical elements is described, and experimental results are presented.

PMID- 18059844
TI  - Aperture scaling effects with monolithic periodically poled lithium niobate
      optical parametric oscillators and generators.
AB  - We used elliptical beams to demonstrate aperture scaling effects in nanosecond
      single-grating and multigrating periodically poled lithium niobate (PPLN)
      monolithic optical parametric oscillators and generators. Increasing the cavity
      Fresnel number in single-grating crystals broadened both the beam divergence and
      the spectral bandwidth. Both effects are explained in terms of the phase-matching
      geometry. These effects are suppressed when a multigrating PPLN crystal is used
      because the individual gratings provide small effective subapertures. A flood
      pumped multigrating optical parametric generator displayed a low output beam
      divergence and contained 19 pairs of signal and idler frequencies.

PMID- 18059845
TI  - Large optical second-order nonlinearity of poled WO3-TeO2 glass.
AB  - Second-harmonic generation, one of the second-order nonlinear optical properties
      of thermally and electrically poled WO>(3)-TeO>(2) glasses, has been examined. We
      poled glass samples with two thicknesses (0.60 and 0.86 mm) at various
      temperatures to explore the effects of external electric field strength and
      poling temperature on second-order nonlinearity. The dependence of second
      harmonic intensity on the poling temperature is maximum at a specific poling
      temperature. A second-order nonlinear susceptibility of 2.1 pm/V was attained for
      the 0.60-mm-thick glass poled at 250 degrees C. This value is fairly large
      compared with those for poled silica and tellurite glasses reported thus far. We
      speculate that the large third-order nonlinear susceptibility of WO>(3)- TeO>(2)
      glasses gives rise to the large second-order nonlinearity by means of a X((2)) =
      3X((3)) E(dc) process.

PMID- 18059846
TI  - Large Kerr effect in bulk Se-based chalcogenide glasses.
AB  - High-speed optical communication requires ultrafast all-optical processing and
      switching capabilities. The Kerr nonlinearity, an ultrafast optical nonlinearity,
      is often used as the basic switching mechanism. A practical, small device that
      can be switched with ~1-pJ energies requires a large Kerr effect with minimal
      losses (both linear and nonlinear). We have investigated theoretically and
      experimentally a number of Se-based chalcogenide glasses. We have found a number
      of compounds with a Kerr nonlinearity hundreds of times larger than silica,
      making them excellent candidates for ultrafast all-optical devices.

PMID- 18059847
TI  - Conversion of unpolarized light to polarized light with greater than 50%
      efficiency by photorefractive two-beam coupling.
AB  - All known polarizers operate through a separation of orthogonal electric field
      components, one of which is subsequently discarded. As a result, 50% of the
      unpolarized incident light is wasted in the process of conversion to polarized
      light. We demonstrate a new method by which we use the optical power in the
      ordinarily discarded component as the pump to amplify the retained component
      through photorefractive two-beam coupling to achieve greater than 50% throughput.

PMID- 18059848
TI  - Highly efficient optical power transfer to whispering-gallery modes by use of a
      symmetrical dual-coupling configuration.
AB  - We report that greater than 99.8% optical power transfer to whispering-gallery
      modes was achieved in fused-silica microspheres by use of a dual-tapered-fiber
      coupling method. The intrinsic cavity loss and the taper-to-sphere coupling
      coefficient are inferred from the experimental data. It is shown that the low
      intrinsic cavity loss and the symmetrical dual-coupling structure are crucial for
      obtaining the high coupling efficiency.

PMID- 18059849
TI  - Er-Al-codoped silicate planar light waveguide-type amplifier fabricated by radio
      frequency sputtering.
AB  - A planar light waveguide-type optical amplifier was designed and fabricated. A
      core layer of Er-Al-codoped SiO>(2) glass was deposited onto a silica cladding
      layer by rf sputtering. In the Er-doped core layer the average Er and Al
      concentrations were 0.77 and 11.37 wt.%, respectively. We achieved 5 dB of gain
      with 20 mW of 980-nm pump power by using -20 dBm of 1546-nm input signal power.

PMID- 18059850
TI  - Determination and optimization of mode matching into optical cavities by
      heterodyne detection.
AB  - We report on a novel high-sensitivity method to characterize and improve mode
      matching into optical cavities. This method is based on heterodyne detection of
      cylindrical transverse cavity modes. A specially designed annular-segmented
      photodiode is used to measure the amplitude of nonresonant modes reflected by the
      cavity. Our measurements allow us to optimize cavity mode matching to nearly
      99.98% and will play an important diagnostic role in gravitational-wave
      detectors.

PMID- 18059851
TI  - Collinear type II second-harmonic-generation frequency-resolved optical gating
      for the characterization of sub-10-fs optical pulses.
AB  - For the first time to our knowledge, we demonstrate a collinear frequency
      resolved optical gating (FROG) technique that is suitable for the
      characterization of sub-10-fs pulses. This FROG variant does not suffer from
      geometrical blurring effects, and a temporal resolution of 1 fs can be achieved
      without the need for additional aperturing. The apparatus is suitable for
      subnanojoule pulse energies. We apply this technique for the full
      characterization of pulses from a Kerr-lens mode-locked Ti:sapphire laser.

PMID- 18059852
TI  - Sampling a terahertz dipole transition with subcycle time resolution.
AB  - We present a time-resolved technique to measure optical excitation processes with
      a time resolution shorter than the oscillation period of the exciting light. Our
      terahertz (THz) experiments fully resolve the polarization dynamics of electrons
      in semiconductor heterostructures when they are excited by a THz pulse. The time
      resolution of the polarization enables us to deduce the population dynamics of
      the excited state, which includes the dynamics of a virtual population in the
      case of off-resonant excitation.

PMID- 18059853
TI  - Double Gires-Tournois interferometer negative-dispersion mirrors for use in
      tunable mode-locked lasers.
AB  - We report the implementation and operation of novel superhigh-reflectivity
      negative-dispersion dielectric mirrors for use in tunable ultrafast laser
      systems. The mirror structure is divided into two distinct regions: an underlying
      superhigh-reflectivity dielectric quarter-wavelength stack and an overlying
      negative-dispersion section consisting of only a few layers and forming simple
      multiple Gires-Tournois interferometers. The example that we present was designed
      for operation from 800 to 900 nm and has a near-constant group-delay dispersion
      of -40 fs(2) and a peak reflectivity greater than 99.99%. We show a comparison of
      the predicted and the measured mirror performance and application of these
      mirrors in a mode-locked Ti:sapphire laser tunable from 805 to 915 nm.

PMID- 18059854
TI  - Can the Wigner transform of a two-dimensional rotationally symmetric beam be
      fully recovered from the Wigner transform of its one-dimensional approximation?
AB  - It is shown that the full four-dimensional Wigner transform of a coherent,
      rotationally symmetric light beam can be completely recovered by measurement, in
      one step, of the Wigner transform of an equivalent one-dimensional light beam.
      The method of generating this equivalent light beam from a two-dimensional
      circular light beam is presented.

PMID- 18059856
TI  - Efficient reduction of interactions in dispersion-managed links through in-line
      filtering and synchronous intensity modulation.
AB  - The effect of combined use of in-line filtering and synchronous intensity
      modulation on interactions is investigated both analytically and numerically in a
      40-Gbit/s dispersion-managed link. Numerical results confirm analytical
      predictions and show that interactions are efficiently suppressed.

PMID- 18059855
TI  - Conversion of bright nondiffracting beams into dark nondiffracting beams by use
      of the topological properties of polarized light.
AB  - We present a method for the generation of an axial phase dislocation on a wave
      front, which is induced by topological properties of polarized light. This effect
      is shown to be useful for conversion of bright nondiffracting beams into dark
      nondiffracting beams. Experiments showing the generation of dark nondiffracting
      beams have been performed.

PMID- 18059857
TI  - Solitons and polarization mode dispersion.
AB  - Analytical expressions are presented for Manakov solitons perturbed by
      polarization mode dispersion (PMD). Comparison is made with computer simulations.
      Dispersion-managed solitons are also studied. It is concluded that at high bit
      rates solitons are superior to linear return-to-zero propagation with regard to
      PMD.

PMID- 18059858
TI  - Modulational instability in a transmission system with semiconductor optical
      amplifiers and in-line filters.
AB  - Modulational instability of continuous waves in transmission systems with
      semiconductor optical amplifiers and in-line filters was theoretically and
      experimentally analyzed. Stable and unstable domains were identified. Even in the
      normal-dispersion region, modulationally unstable domains can exist for an
      appropriate filter detuning.

PMID- 18059859
TI  - Fourth-order dispersion suppression of ultrashort optical pulses by second-order
      dispersion and cosine phase modulation.
AB  - A technique for significantly suppressing severe fourth-order dispersion of
      ultrashort optical pulses in long-distance transmission is analyzed by use of the
      quadratic phase from the excess second-order dispersion of the fiber link in
      conjunction with synchronously applied cosine phase modulation of temporally
      stretched pulses. Numerical simulation predicts much improved transmission of 250
      fs pulses at 5-10-GHz repetition rates over ~100 km of fiber by pi-3.5pi phase
      modulation.

PMID- 18059860
TI  - Measurement of the chromatic dispersion of an optical fiber by use of a Sagnac
      interferometer employing asymmetric modulation.
AB  - We describe a novel method, based on asymmetric modulation in a Sagnac
      interferometer, that measures the chromatic dispersion of single-mode fibers. The
      interferometer incorporates a phase modulator and a test fiber, so the dispersion
      can be determined from the interference fringe seen when a sweep rf signal is
      applied to the modulator. This technique provides picosecond temporal resolution
      without the need for any fast diagnostic equipment and is capable of accurately
      measuring the average dispersion of fibers several kilometers long.

PMID- 18059861
TI  - Large increase in photosensitivity through massive hydroxyl formation.
AB  - We report a large increase in photosensitivity of germanium-doped silicate fibers
      by rapid heat treatment of hydrogen-loaded fibers at 1000 degrees C before
      exposure of the fibers to 242-nm radiation. The increase in photosensitivity is
      compared with thermally induced absorption caused by introduction of massive
      amounts of hydroxyl species. The absorption loss was measured to be 0.02 dB/cm
      mol.% OH at 1.55 mum. Strong gratings (Dn > 1 x 10(-4)) in germanium-free
      phosphorous-doped fibers in the presence of 242-nm radiation have also been
      manufactured by this technique.

PMID- 18059862
TI  - Broadband monolithic acousto-optic tunable filter.
AB  - Broadband monolithic acousto-optic tunable filters that combine a piezoelectric
      transducer array and an acousto-optic interaction medium in a single crystal have
      been investigated. A linearly chirped acoustic superlattice with an optical
      tuning range of lambda = 1.3-1.6 mum was formed by domain inversion in LiNbO(3) .
      X-propagating longitudinal acoustic waves are excited in a crossed-field scheme
      by a rf E(y) field applied to the superlattice and couple collinearly propagating
      e- and o-polarized optical modes. At mu = 1.319 mum and mu = 1.55 mum the
      spectral bandwidths (FWHM) were 1.54 and 2.3 nm, respectively. A relative
      conversion efficiency of 43%/W and a maximum conversion efficiency of 51% were
      measured at 1.319 mum.

PMID- 18059863
TI  - Frequency comb generation using femtosecond pulses and cross-phase modulation in
      optical fiber at arbitrary center frequencies.
AB  - A technique is presented for generating optical frequency combs centered at
      arbitrary wavelengths by use of cross-phase modulation (XPM) between a
      femtosecond pulse train and a cw laser beam by copropagating these signals
      through an optical fiber. We report results from use of this method to place a 90
      MHz frequency comb on an iodine-stabilized Nd:YAG laser at 1064 nm and on a
      frequency-doubled Nd:YVO(4) laser at 532 nm. XPM is verified to be the comb
      generating process, and the width of the frequency comb is measured and compared
      with theory. The spacing of the frequency comb is compared with the femtosecond
      source, and a frequency measurement with this comb is demonstrated.

PMID- 18059864
TI  - Cancellation of laser dither modulation from optical frequency standards.
AB  - We demonstrate the removal of the dither modulation from an iodine-stabilized He
      Ne laser by using a frequency-modulated acousto-optic modulator and feed-forward
      techniques. This procedure reduces the linewidth of the beat between this laser
      and a flywheel He-Ne laser from 6 MHz to 8 kHz, the undithered beat linewidth
      being ~7 kHz. Dither suppression greatly reduces counter errors during beat
      measurements from stroboscopic effects between the counter's gate and the
      frequency of the dither modulation and increases the utility of the already
      formidable array of dithered laser frequency standards by making locking to them
      an easier task.

PMID- 18059865
TI  - Wide-range amplified spontaneous emission wavelength tuning in a solid-state dye
      waveguide.
AB  - Amplified spontaneous emission (ASE) in an organic-dye- (DCM-) doped poly(methyl
      methacrylate)/silica-gel hybrid material planar waveguide was investigated. ASE
      wavelength control and tuning in a wedge waveguide were realized. The tuning
      range of the waveguide can reach as much as 30 nm. This method can be applied to
      wide-range wavelength tuning in solid-state tunable lasers.

PMID- 18059866
TI  - Optical vortices generated by dislocations in a cholesteric liquid crystal.
AB  - We report the observation of optical vortices in a laser beam propagating through
      the stripe pattern of a cholesteric liquid crystal. The liquid crystal is
      confined in a cell with homogeneous boundary conditions and forms a diffraction
      phase grating. Optical vortices are produced by edge dislocations of the
      cholesteric grating. The vortices show up as spots of zero light intensity in the
      diffraction maxima. There is one spot in each +1 and -1 diffraction maximum and
      two spots in diffraction maxima +2 and -2.

PMID- 18059867
TI  - Membrane imaging by simultaneous second-harmonic generation and two-photon
      microscopy.
AB  - We demonstrate that simultaneous second-harmonic generation (SHG) and two-photon
      excited fluorescence (TPEF) can be used to rapidly image biological membranes
      labeled with a styryl dye. The SHG power is made compatible with the TPEF power
      by use of near-resonance excitation, in accord with a model based on the theory
      of phased-array antennas, which shows that the SHG radiation is highly
      structured. Because of its sensitivity to local asymmetry, SHG microscopy
      promises to be a powerful tool for the study of membrane dynamics.

PMID- 18059868
TI  - Exploitation of the Z-scan technique as a method to optically probe pK(a) in
      organic materials: application to porphyrin derivatives.
AB  - We demonstrate the use of the Z-scan technique as a method to measure a chemical
      parameter, the pK(a) value, that characterizes the equilibrium constant in acid
      base reactions. The measurements were performed with picosecond pulses at 532 nm
      in Fe(III)-meso-tetrakis(4-N-methyl-pyridyl) porphyrin. The results were compared
      with linear absorption measurements and electron paramagnetic resonance, the
      usual techniques employed to determine pK(a) values in aqueous solutions, and
      showed excellent agreement.

PMID- 18059869
TI  - Pixellike parametric generator based on controlled spatial-soliton formation.
AB  - We report the observation of a stable matrix of diffraction-limited solitary
      beams in a monolithic, single-pass, parametric amplifier pumped by a spatially
      modulated beam.

PMID- 18059870
TI  - Modified theory of photoinduced molecular polar alignment in azo polymers.
AB  - An improvement on the simplified theory of all-optical poling [Chem. Phys. Lett.
      286, 415 (1998)] is proposed. In this improvement the influence of the cis isomer
      is taken into account in the process of photoinduced molecular polar alignment.
      An analytical expression for the induced polar order in the steady-state regime
      is derived. This expression shows that, although the contribution to the
      photoinduced second-order susceptibility from the cis state itself can be
      neglected, the population of the cis state plays an important role. This result
      suggests the possibility that one can improve the induced polar order by
      increasing the poling temperature, so that thermal-assisted optical poling can be
      explained.

PMID- 18059871
TI  - Systematic behavior of electro-optic chromophore photostability.
AB  - The wavelength dependence of the one-photon absorption-induced photodegradation
      rate has been measured from the visible to the near IR for a variety of electro
      optic chromophore-doped polymers. Systematic behavior is identified. The lifetime
      of the electro-optic activity is found to increase exponentially over 4-6 orders
      of magnitude for wavelengths ranging from peak of absorption, typically in the
      visible, to ~1000 nm. Many popular chromophores developed for electro-optics over
      the past 10 years are compared.

PMID- 18059872
TI  - Critical power for self-focusing in bulk media and in hollow waveguides.
AB  - We determine the threshold power for self-focusing collapse both in a bulk medium
      and in a hollow-core waveguide for various spatial profiles. We find that the
      threshold power for collapse in the waveguide is always equal to the lower-bound
      prediction for a bulk medium.

PMID- 18059873
TI  - Highly efficient infrared-to-visible energy upconversion in Er(3+):Y(2)O(3).
AB  - Very intense green and red emission was observed at room temperature from the
      (4)S(3/2) and (4)F(9/2) levels of Er(3+):Y(2)O(3). A cw diode laser at 975 nm was
      used as a pump for resonant sequential excitation of the (4)I(11/2) and (4)F(7/2)
      levels. The fluorescence was easily visible to the naked eye, even with 27 mW of
      excitation power. It was found that at 850 mW of cw excitation power the total
      luminance was 39,000 cd/m(2). This corresponds to ~100 muW of green emission and
      270 muW of red emission.

PMID- 18059874
TI  - Extended mode-hop-free tuning by use of a dual-cavity, pump-enhanced optical
      parametric oscillator.
AB  - We report extended mode-hop-free tuning in a continuous-wave, pump-enhanced
      optical parametric oscillator (PE-OPO). We employ a dual-cavity configuration to
      allow independent control of the resonant pump and signal fields, and so we can
      suppress frequent mode hops in the signal as the pump is tuned in frequency. With
      the signal field clamped in frequency by an uncoated etalon, the idler field can
      be scanned smoothly through a range of 10.8 GHz. The PE-OPO outputs can also be
      tuned coarsely from 1.01 to 1.18 mum in the signal and from 2.71 to 3.26 mum and
      4.07 to 5.26 mum in the idler. We find that increased idler absorption only
      slightly increases the oscillation threshold.

PMID- 18059875
TI  - Filter synthesis for periodically coupled microring resonators.
AB  - The theory of filter synthesis using periodically coupled microring resonators is
      developed as a means to overcome the fabrication sensitivities inherent in
      conventional higher-order filters, while still achieving desirable spectral
      characteristics. Each resonator in the array can compensate for deficiencies in
      any of the others. These filters exhibit a boxlike shape and very high extinction
      ratios.

PMID- 18059876
TI  - Experimental verification of Rayleigh scattering cross sections.
AB  - The cavity-ringdown technique is applied to measure Rayleigh extinctions of Ar,
      N(2), and SF(6) in the 560-650-nm region at 294 K. It is shown that experimental
      and calculated Rayleigh scattering cross sections agree within an experimental
      uncertainty of 1% (for SF(6), 3%).

PMID- 18059877
TI  - Saturated-absorption spectroscopy with low-power difference-frequency radiation.
AB  - We report high-resolution saturated-absorption spectra recorded by use of a few
      microwatts of radiation generated in a single pass by difference-frequency
      mixing. These results were obtained without the use of buildup cavities for the
      nonlinear mixing or for the saturation spectroscopy. We show high-quality
      saturated-absorption signals for the fundamental rovibrational band of CO(2) near
      4.3 mum. Convenient sources and frequency-conversion devices open new
      possibilities for sub-Doppler spectroscopy in the infrared.

PMID- 18059878
TI  - Video rate depth-resolved two-dimensional imaging through turbid media by
      femtosecond parametric amplification.
AB  - We report two-dimensional imaging through a liquid scattering medium by
      noncollinear femtosecond parametric amplification in a reflection configuration.
      The experiment presented permits direct observation at video rate of two
      dimensional images with 24-mum depth resolution and 90-mum transverse resolution
      for an area with a 2.5-mm diameter on the object. These resolutions are
      achievable through a turbid phantom with a depth near 12 scattering mean free
      paths in double pass.

PMID- 18059879
TI  - Dense plasma diagnostics with an amplitude-division soft-x-ray laser
      interferometer based on diffraction gratings.
AB  - We report the demonstration of an amplitude-division soft-x-ray interferometer
      that can be used to generate high-contrast interferograms at the wavelength of
      any of the saturated soft-x-ray lasers (5.6-46.9 nm) that are available at
      present. The interferometer, which utilizes grazing-incidence diffraction
      gratings as beam splitters in a modified Mach-Zehnder configuration, was used in
      combination with a tabletop 46.9-nm laser to probe a large-scale (~2.7-mm-long)
      laser-created plasma.

PMID- 18059880
TI  - Optimal synthesis of three-dimensional complex amplitude distributions.
AB  - The synthesis of three-dimensional (3-D) light distributions is important for
      many applications. For example, in scanning applications it is preferable that
      the scanning beam preserve its characteristics over a large distance to yield
      elongated scanning range. It is evident that any 3-D light distribution must
      satisfy the wave equation or, in second-order approximation, the Fresnel
      diffraction formula. Thus many desirable 3-D light distributions may not be
      realizable. We propose a single optical element (OE) that synthesizes a physical
      beam within a certain 3-D region. The OE provides the optimal physical beam in
      comparison with a desired one in the sense of minimal mean-square error.

PMID- 18059881
TI  - A reciprocity inequality for Gaussian Schell-model beams and some of its
      consequences.
AB  - A reciprocity inequality is derived, involving the effective size of a planar,
      secondary, Gaussian Schell-model source and the effective angular spread of the
      beam that the source generates. The analysis is shown to imply that a fully
      spatially coherent source of that class (which generates the lowest-order Hermite
      Gaussian laser mode) has certain minimal properties.

PMID- 18059882
TI  - Radiative transfer over small distances from a heated metal.
AB  - Published works have predicted that the radiative transfer from a heated metal to
      a lossless dielectric a short distance away is many orders of magnitude times the
      free-space Planck density. It is shown analytically that the radiative transfer
      from a heated metal to a lossless dielectric of index n(3) is n(3)(2)e(13) times
      the free-space Planck density, where e(13) is the emissivity of the metal
      radiating into the lossless dielectric. This radiative transfer is never larger
      than n(3)(2) (approximately one order of magnitude for semiconductors in the
      infrared) times the free=space Planck density. The expressions presented show
      that the maximum radiative transfer from a lossy metallic heat source with a
      dielectric function of imaginary part ?(I) must be proportional to n(3)(3)/
      radical?(I), of which a factor of n(3)(2) arises from the power density within a
      dielectric and a factor of n(3)/ radical?(I) arises from the emissivity of a
      metal radiating directly into a dielectric.

PMID- 18059883
TI  - Local plasmon sensor with gold colloid monolayers deposited upon glass
      substrates.
AB  - A new optical sensor that uses local plasmon resonance is proposed. A peak that
      is due to the local plasmon resonance appears in the absorption spectrum of a
      gold colloid suspension in the visible region, and its height and wavelength
      depend on the refractive index of the suspension. These properties are used for
      optical sensors. We used gold colloid monolayers in which colloidal gold
      particles a few tens of nanometers in diameter were immobilized upon a glass
      slide by a functional organic coupling agent. We measured the absorption spectra
      of the the gold colloid monolayers, which were immersed in liquid samples or
      coated with thin films. We observed increases of both the resonance wavelength
      and the absorbance as the refractive indices of the sample liquids or the
      thickness of the coated films increased. The proportional constants of the
      resonance wavelength to the film thickness were 3.6 and 5.7 for a 13.9- and a
      20.2-nm gold colloid monolayer, respectively.

PMID- 18059884
TI  - Amplification of enhanced backscattering from a dye-doped polymer bounded by a
      rough surface.
AB  - We report the experimental study of the enhanced backscattering from a random
      rough surface through a laser dye-doped polymer. The sample is a slice of
      pyrromethene-doped polymer coupled with a two-dimensional rough gold layer with a
      large slope. When the sample is illuminated with an s-polarized He-Ne laser and
      pumped by a cw argon-ion laser, amplified backscattering is observed. The
      enhanced backscattering peak increases sharply and its width narrows for a sample
      with low dielectric constant |?(2)|.

PMID- 18059885
TI  - Ultrasound tagged light imaging in turbid media in a reflectance geometry.
AB  - A combination of light and focused ultrasound waves provides a unique way to
      obtain directly three-dimensional absorption data in a turbid medium. We present
      the combination of an ultrasound wave and light in which both the input and the
      output optodes are on the same side of the sample (reflectance geometry). This
      technique permits local detection in depth of the presence of a purely absorbing
      object, without further mathematical processing. It is a promising technique for
      medical imaging and monitoring of tissues.

PMID- 18059886
TI  - Diffractive lens fabricated with binary features less than 60 nm.
AB  - We designed, fabricated, and characterized a binary diffractive lens with
      features less than 60 nm. The lens was designed for operation in the red portion
      of the spectrum. Experimental measurements of lens performance agree with
      predictions generated by rigorous models of diffraction.

PMID- 18059887
TI  - Measurements of beat length and perturbation length in long single-mode fibers.
AB  - Experimental results of measurement of the beat length and the differential group
      delay of several types of long single-mode fiber are presented. The proposed
      measurement technique is based on a polarization-sensitive analysis of the
      backscattered signal and allows one to calculate the correlation length of the
      random birefringence affecting the fiber.

PMID- 18059888
TI  - Polarization-maintaining, double-clad fiber amplifier employing externally
      applied stress-induced birefringence.
AB  - We report a new approach to obtaining linear-polarization operation of a rare
      earth-doped fiber amplifier in which the gain fiber is coiled under tension to
      induce birefringence. We demonstrated this method by constructing an Er/Yb-doped,
      double-clad, single-mode fiber amplifier with an output power of 530 mW and a
      polarization extinction ratio of >17 dB (when seeded with linearly polarized
      light) at a wavelength of ~1.5 microm . The technique is achromatic, permits
      single- or multiple-pass operation of the amplifier, requires no additional
      components in the optical path, leaves the fiber ends unobstructed, and is
      inexpensive to implement.

PMID- 18059889
TI  - Electrostrictive response in single-mode ring-index-profile fibers.
AB  - We have theoretically investigated, for what is to our knowledge the first time,
      the electrostrictive response in a single-mode ring-core fiber. We found that the
      electrostrictive response function differs strongly from those of standard fibers
      with a Gaussian light-intensity profile.

PMID- 18059890
TI  - Wavelength conversion by use of four-wave mixing in a novel optical loop
      configuration.
AB  - A novel loop configuration for generation of four-wave mixing (FWM) and
      suppression of input pump wave, signal wave, and amplified spontaneous emission
      is proposed and experimentally demonstrated. The novel loop configuration is very
      simple and functions independently of the wavelengths of the pump and the signal
      waves. By use of the novel loop configuration, nonreturn-to-zero wavelength
      conversion at 10 Gbits/s is achieved. The FWM-to-pump ratio, the FWM-to-signal
      ratio, and the signal-to-noise ratio are improved by 17.9, 18.8, and 8.2 dB,
      respectively. A principle experiment of wavelength conversion of four
      simultaneous channels is demonstrated.

PMID- 18059891
TI  - Phase-restricted heterogeneous correlation.
AB  - We introduce a new phase-restricted algorithm for producing a heterogeneous
      correlation filter that permits new in-class members to be added without changing
      the phase of the filter. This heterogeneous correlation filter uses amplitude
      modulation both to enhance in-class cross correlations and to suppress selected
      out-of-class correlations. This new algorithm should substantially improve the
      performance of existing class-associative correlators and improve their
      operation.

PMID- 18059892
TI  - Tunable stimulated-Brillouin-scattering resonator started by feedback provided by
      Bragg scattering from the dynamic grating within an active medium.
AB  - We report a tunable stimulated-Brillouin-scattering resonator that does not
      require a starting mirror or a wavelength selector. The resonator is based on the
      Bragg scattering from the dynamic grating within the active medium itself. The
      laser dye (Rhodamine 6G dissolved in ethanol) was utilized as the active medium
      and was pumped by a frequency-doubled Nd:YAG laser. The quality factor (M(2)) of
      the output beam was 2.2. A single short pulse (<1 ns) with a pumping efficiency
      of ~4% was observed.

PMID- 18059893
TI  - Three-cascaded 1407-nm Raman laser based on phosphorus-doped silica fiber.
AB  - We report a laser-diode-pumped 1407-nm Raman fiber laser with an output power of
      1 W. In this three-cascaded cw Raman laser, based on a single active phosphorus
      doped silica fiber, for the first time to the authors' knowledge successive
      generation of Stokes components of essentially different frequency shifts (1330
      and 490cm(-1)) has been realized. These Stokes components are associated with
      both constituents (P(2)O(5) and SiO(2)) of the fiber core glass.

PMID- 18059894
TI  - Spectral beam combining of a broad-stripe diode laser array in an external
      cavity.
AB  - The outputs from an 11-element, linear diode laser array with broad stripes have
      been beam combined into a single beam with a beam quality of ~20x diffraction
      limited in the plane of the junction. This beam combining was achieved by use of
      a common external cavity containing a grating, which simultaneously forces each
      array element to operate at a different, but controlled, wavelength and forces
      the beams from all the elements to overlap and propagate in the same direction.
      The power in the combined beam was 50% of the output from the bare laser array.

PMID- 18059895
TI  - Space-selective growth of frequency-conversion crystals in glasses with
      ultrashort infrared laser pulses.
AB  - We report on space-selective growth of a second-harmonic-generation beta
      BaB(2)O(4) (BBO) crystal inside a BaO-Al(2)O(3)-B(2)O(3) glass sample at the
      focal point of an 800-nm femtosecond laser beam. A spherical heated region was
      formed during the focused laser irradiation through observation with an optical
      microscope. We moved the heated region by changing the position of the focal
      point of the laser beam relative to the glass sample. We grew BBO crystal
      continuously in the glass sample by adjusting the moving speed of the heated
      zone. Our results demonstrate that functional crystals can be formed three
      dimensionally in glasses by use of a nonresonant ultrashort pulsed laser.

PMID- 18059896
TI  - Optical second-harmonic-generation probe of two-dimensional ferroelectricity.
AB  - Optical second-harmonic generation (SHG) is used as a noninvasive probe of two
      dimensional (2D) ferroelectricity in Langmuir-Blodgett (LB) films of the
      copolymer vinylidene fluoride with trifluoroethylene. The surface 2D
      ferroelectric-paraelectric phase transition in the topmost layer of the LB films
      and a thickness-independent (almost 2D) transition in the bulk of these films are
      observed in temperature studies of SHG.

PMID- 18059897
TI  - Electrically controlled surface diffraction gratings in nematic liquid crystals.
AB  - Photorefractive diffraction gratings were studied in cells of homeotropically
      aligned pentyl-cyanobiphenyl liquid crystal. These holographic gratings were
      induced by the simultaneous and nonsimultaneous application of dc and coherent
      optical electric fields. The observed behavior was consistent with a
      predominantly surface-mediated photorefractive effect. Beam coupling was observed
      in all cases and led to a model involving screened and unscreened interfacial
      trapped charges driving a modulation of the easy axis. Holographic gratings could
      be switched on and off by the application of a small voltage.

PMID- 18059898
TI  - Observation of bound states of interacting vector solitons.
AB  - We report experimental observation of bound states formed by two well-separated
      vector spatial solitons as the result of a force balance between vector-soliton
      components. We also demonstrate a link between such soliton bound states and two
      hump, two-mode solitons, along with the induced coherence effect observed for
      incoherently interacting solitons.

PMID- 18059899
TI  - Diffraction properties of highly birefringent liquid-crystal composite gratings.
AB  - We have fabricated electrically switchable holographic gratings, using Polaroid
      Corporation's DMP-128 photopolymer filled with the nematic liquid crystal E7. It
      is shown that a coupled-wave theory that includes the effects of the
      birefringence of the liquid crystal must be used to explain the diffraction
      properties of these anisotropic volume gratings. Furthermore, a detailed
      comparison of theory and experiment provides information about the alignment of
      the liquid crystal within the polymer host.

PMID- 18059900
TI  - Generation of 90-fs pulses from a mode-locked diode-pumped
      Yb(3+):Ca(4)GdO(BO(3))(3) laser.
AB  - A diode-pumped Yb>(3+):Ca(4)GdO(BO>(3))(3) (Yb:GdCOB) laser generating 90-fs
      pulses at a center wavelength of 1045 nm is demonstrated. This is, to our
      knowledge, the shortest pulse duration obtained from an ytterbium laser with a
      crystalline host. This laser is mode locked with a high-finesse semiconductor
      saturable-absorber mirror and emits 40 mW of average power at a repetition rate
      of 100 MHz.

PMID- 18059901
TI  - Single-shot measurement of terahertz electromagnetic pulses by use of electro
      optic sampling.
AB  - We demonstrate a simple scheme for capturing the temporal waveforms of a freely
      propagating terahertz electromagnetic transient in a single shot. The method
      relies on electro-optic sampling in a noncollinear geometry for the terahertz
      radiation and the visible probe beam, coupled with multichannel detection. The
      approach provides time resolution that is comparable to that of conventional
      electro-optic sampling measurements.

PMID- 18059902
TI  - Human linear template with mammographic backgrounds estimated with a genetic
      algorithm.
AB  - We estimated human observer linear templates underlying the detection of a
      realistic, spherical mass signal with mammographic backgrounds. Five trained
      naive observers participated in two-alternative forced-choice (2-AFC) detection
      experiments with the signal superimposed on synthetic, clustered lumpy
      backgrounds (CLBs) in one condition and on nonstationary real mammographic
      backgrounds in another. Human observer linear templates were estimated using a
      genetic algorithm. A variety of common model observer templates were computed,
      and their shapes and associated performances were compared with those of the
      human observer. The estimated linear templates are not significantly different
      for stationary CLBs and real mammographic backgrounds. The estimated performance
      of the linear template compared with that of the human observers is within 5% in
      terms of percent correct (Pc) for the 2-AFC task. Channelized Hotelling models
      can fit human performance, but the templates differ considerably from the human
      linear template. Due to different local statistics, detection efficiency is
      significantly higher on nonstationary real backgrounds than on globally
      stationary synthetic CLBs. This finding emphasizes that nonstationary backgrounds
      need to be described by their local statistics.

PMID- 18059903
TI  - Classification images for simple detection and discrimination tasks in correlated
      noise.
AB  - We use the classification image technique to investigate the effect of white
      noise and various correlated Gaussian noise textures (low-pass, high-pass, and
      band-pass) on observer performance in detection and discrimination tasks. For
      these tasks, performance is generally enhanced by an observer's ability to
      "prewhiten" correlated noise as part of the formation of a decision variable. We
      find that observer efficiency in these tasks is well represented by the measured
      classification images and that human observers show strong evidence of adaptation
      to different correlated noise textures. This adaptation is captured in the
      frequency weighting of the classification images.

PMID- 18059904
TI  - Selection of image fusion quality measures: objective, subjective, and metric
      assessment.
AB  - Accurate quality assessment of fused images, such as combined visible and
      infrared radiation images, has become increasingly important with the rise in the
      use of image fusion systems. We bring together three approaches, applying two
      objective tasks (local target analysis and global target location) to two
      scenarios, together with subjective quality ratings and three computational
      metrics. Contrast pyramid, shift-invariant discrete wavelet transform, and dual
      tree complex wavelet transform fusion are applied, as well as levels of JPEG2000
      compression. The differing tasks are shown to be more or less appropriate for
      differentiating among fusion methods, and future directions pertaining to the
      creation of task-specific metrics are explored.

PMID- 18059905
TI  - Application of the Hotelling and ideal observers to detection and localization of
      exoplanets.
AB  - The ideal linear discriminant or Hotelling observer is widely used for detection
      tasks and image-quality assessment in medical imaging, but it has had little
      application in other imaging fields. We apply it to detection of planets outside
      of our solar system with long-exposure images obtained from ground-based or space
      based telescopes. The statistical limitations in this problem include Poisson
      noise arising mainly from the host star, electronic noise in the image detector,
      randomness or uncertainty in the point-spread function (PSF) of the telescope,
      and possibly a random background. PSF randomness is reduced but not eliminated by
      the use of adaptive optics. We concentrate here on the effects of Poisson and
      electronic noise, but we also show how to extend the calculation to include a
      random PSF. For the case where the PSF is known exactly, we compare the Hotelling
      observer to other observers commonly used for planet detection; comparison is
      based on receiver operating characteristic (ROC) and localization ROC (LROC)
      curves.

PMID- 18059906
TI  - Channelized-ideal observer using Laguerre-Gauss channels in detection tasks
      involving non-Gaussian distributed lumpy backgrounds and a Gaussian signal.
AB  - We investigate a channelized-ideal observer (CIO) with Laguerre-Gauss (LG)
      channels to approximate ideal-observer performance in detection tasks involving
      non-Gaussian distributed lumpy backgrounds and a Gaussian signal. A Markov-chain
      Monte Carlo approach is employed to determine the performance of both the ideal
      observer and the CIO using a large number of LG channels. Our results indicate
      that the CIO with LG channels can approximate ideal-observer performance within
      error bars, depending on the imaging system, object, and channel parameters. The
      CIO also outperforms a channelized-Hotelling observer using the same channels. In
      addition, an alternative approach for estimating the CIO is investigated. This
      approach makes use of the characteristic functions of channelized data and
      employs an approximation method to the area under the receiver operating
      characteristic curve. The alternative approach provides good estimates of the
      performance of the CIO with five LG channels. However, for large channel cases,
      more efficient computational methods need to be developed for the CIO to become
      useful in practice.

PMID- 18059907
TI  - Signal and noise transfer in spatiotemporal quantum-based imaging systems.
AB  - Fourier-based transfer theory is extended into the temporal domain to describe
      both spatial and temporal noise processes in quantum-based medical imaging
      systems. Lag is represented as a temporal scatter in which the release of image
      quanta is delayed according to a probability density function. Expressions
      describing transfer of the spatiotemporal Wiener noise power spectrum through
      quantum gain and scatter processes are derived. Lag introduces noise correlations
      in the temporal domain in proportion to the correlated noise component only. The
      effect of lag is therefore dependent on both spatial and temporal physical
      processes. A simple model of a fluoroscopic system shows that image noise is
      reduced by a factor that is similar to Wagner's information bandwidth integral,
      which depends on the temporal modulation transfer function.

PMID- 18059908
TI  - Performance of focus measures in the presence of nondefocus aberrations.
AB  - The purposes of the study were to compare the performance of ten representative
      focus measures in the presence of nondefocus aberrations and to evaluate their
      applicability to the eye. For fixed amounts of nondefocus aberrations, the amount
      of defocus was changed to generate a series of blurred images from which focus
      measure curves were derived. In the presence of small amounts of nondefocus
      aberrations, all focus measures showed unimodal and monotonic behavior, although
      there were large differences in their sensitivity to defocus and effective
      ranges. There were breakdowns in monotonicity and unimodality for some focus
      measures when applied to data from human eyes, while other focus measures could
      detect the shift in the best-focus plane in the blurred image series resulting
      from spherical aberration.

PMID- 18059910
TI  - Analytical-form model observers for decompressed images.
AB  - We report a method for evaluating the performance of model observers for
      decompressed images in analytical form using compression noise statistics. It
      derives test statistics and detectabilities for the ideal observer, the
      nonprewhitening observer, the Hotelling observer, and the channelized Hotelling
      observer (CHO) on decompressed images. The derived CHO performance is validated
      using the Joint Photographic Experts Group (JPEG) compression algorithm. The
      validation results show that the derived CHO receiver operating characteristics
      (ROCs) and areas under ROC curves predict accurately their corresponding
      estimated values. These analytical-form quality measures of decompressed images
      provide a way to optimize compression algorithms analytically, subject to a model
      observer performance criterion. They also provide a theoretical foundation for
      efforts to create a model observer for decompressed images.

PMID- 18059912
TI  - Task-specific information for imaging system analysis.
AB  - Imagery is often used to accomplish some computational task. In such cases there
      are some aspects of the imagery that are relevant to the task and other aspects
      that are not. In order to quantify the task-specific quality of such imagery, we
      introduce the concept of task-specific information (TSI). A formal framework for
      the computation of TSI is described and is applied to three common tasks: target
      detection, classification, and localization. We demonstrate the utility of TSI as
      a metric for evaluating the performance of three imaging systems: ideal
      geometric, diffraction-limited, and projective. The TSI results obtained from the
      simulation study quantify the degradation in the task-specific performance with
      optical blur. We also demonstrate that projective imagers can provide higher TSI
      than conventional imagers at small signal-to-noise ratios.

PMID- 18059909
TI  - Measuring perceived video quality of MPEG enhancement by people with impaired
      vision.
AB  - We used a new method to measure the perceived quality of contrast-enhanced motion
      video. Patients with impaired vision (n=24) and normally sighted subjects (n=6)
      adjusted the level of MPEG-based enhancement of 8 videos (4 min each) drawn from
      4 categories. They selected the level of enhancement that provided the preferred
      view of the videos, using a decreasing-step-size staircase procedure. Most
      patients made consistent selections of the preferred level of enhancement,
      indicating an appreciation of and a perceived benefit from the MPEG-based
      enhancement. The selections varied between patients and were correlated with
      letter contrast sensitivity, but the selections were not affected by training,
      experience, or video category. We measured just noticeable differences directly
      for videos and mapped the image manipulation (enhancement in our case) onto an
      approximately linear perceptual space. These tools and approaches will be of
      value in other evaluations of the image quality of motion video manipulations.

PMID- 18059913
TI  - Blind image quality assessment through anisotropy.
AB  - We describe an innovative methodology for determining the quality of digital
      images. The method is based on measuring the variance of the expected entropy of
      a given image upon a set of predefined directions. Entropy can be calculated on a
      local basis by using a spatial/spatial-frequency distribution as an approximation
      for a probability density function. The generalized Renyi entropy and the
      normalized pseudo-Wigner distribution (PWD) have been selected for this purpose.
      As a consequence, a pixel-by-pixel entropy value can be calculated, and therefore
      entropy histograms can be generated as well. The variance of the expected entropy
      is measured as a function of the directionality, and it has been taken as an
      anisotropy indicator. For this purpose, directional selectivity can be attained
      by using an oriented 1-D PWD implementation. Our main purpose is to show how such
      an anisotropy measure can be used as a metric to assess both the fidelity and
      quality of images. Experimental results show that an index such as this presents
      some desirable features that resemble those from an ideal image quality function,
      constituting a suitable quality index for natural images. Namely, in-focus, noise
      free natural images have shown a maximum of this metric in comparison with other
      degraded, blurred, or noisy versions. This result provides a way of identifying
      in-focus, noise-free images from other degraded versions, allowing an automatic
      and nonreference classification of images according to their relative quality. It
      is also shown that the new measure is well correlated with classical reference
      metrics such as the peak signal-to-noise ratio.

PMID- 18059914
TI  - Signal detection in power-law noise: effect of spectrum exponents.
AB  - Many natural backgrounds have approximately isotropic power spectra of the power
      law form, P(f)=K/f(beta), where f is radial frequency. For natural scenes and
      mammograms, the values of the exponent, beta, range from 1.5 to 3.5. The ideal
      observer model predicts that for signals with certain properties and backgrounds
      that can be treated as random noise, a plot of log (contrast threshold) versus
      log (signal size) will be linear with slope, m, given by: m=(beta-2)/2. This plot
      is referred to as a contrast-detail (CD) diagram. It is interesting that this
      predicts a detection threshold that is independent of signal size for beta equal
      to 2. We present two-alternative forced-choice (2AFC) detection results for human
      and channelized model observers of a simple signal in filtered noise with
      exponents from 1.5 to 3.5. The CD diagram results are in good agreement with the
      prediction of this equation.

PMID- 18059915
TI  - Video quality assessment using a statistical model of human visual speed
      perception.
AB  - Motion is one of the most important types of information contained in natural
      video, but direct use of motion information in the design of video quality
      assessment algorithms has not been deeply investigated. Here we propose to
      incorporate a recent model of human visual speed perception [Nat. Neurosci. 9,
      578 (2006)] and model visual perception in an information communication
      framework. This allows us to estimate both the motion information content and the
      perceptual uncertainty in video signals. Improved video quality assessment
      algorithms are obtained by incorporating the model as spatiotemporal weighting
      factors, where the weight increases with the information content and decreases
      with the perceptual uncertainty. Consistent improvement over existing video
      quality assessment algorithms is observed in our validation with the video
      quality experts group Phase I test data set.

PMID- 18059916
TI  - Multireader multicase variance analysis for binary data.
AB  - Multireader multicase (MRMC) variance analysis has become widely utilized to
      analyze observer studies for which the summary measure is the area under the
      receiver operating characteristic (ROC) curve. We extend MRMC variance analysis
      to binary data and also to generic study designs in which every reader may not
      interpret every case. A subset of the fundamental moments central to MRMC
      variance analysis of the area under the ROC curve (AUC) is found to be required.
      Through multiple simulation configurations, we compare our unbiased variance
      estimates to naive estimates across a range of study designs, average percent
      correct, and numbers of readers and cases.

PMID- 18059917
TI  - Salience measure for assessing scale-based features in mammograms.
AB  - This work assesses the usefulness of an objective, task-based image quality
      measure that is correlated with perceived image quality; the measure uses the
      most salient features contained within a medical image. Contributions include the
      development of a perceptually correlated metric that is useful for quantifying
      the salience of local, low-level visual cues and identifying those spatial
      frequencies that are most distinct and perhaps most relied upon by radiologists
      for decision making. A set of 40 mammograms and registered eye position data from
      nine observers was used to evaluate the salience metric. A parsimonious analysis
      of-variance model explained the variance in the salience results. This analysis
      is generalized to a population of readers and cases. An analysis of salience
      versus time of first eye fixation shows good correlation with true positive
      lesions that were found by experienced readers in less than 2 s.

PMID- 18059918
TI  - Estimation receiver operating characteristic curve and ideal observers for
      combined detection/estimation tasks.
AB  - The localization receiver operating characteristic (LROC) curve is a standard
      method to quantify performance for the task of detecting and locating a signal.
      This curve is generalized to arbitrary detection/estimation tasks to give the
      estimation ROC (EROC) curve. For a two-alternative forced-choice study, where the
      observer must decide which of a pair of images has the signal and then estimate
      parameters pertaining to the signal, it is shown that the average value of the
      utility on those image pairs where the observer chooses the correct image is an
      estimate of the area under the EROC curve (AEROC). The ideal LROC observer is
      generalized to the ideal EROC observer, whose EROC curve lies above those of all
      other observers for the given detection/estimation task. When the utility
      function is nonnegative, the ideal EROC observer is shown to share many
      mathematical properties with the ideal observer for the pure detection task. When
      the utility function is concave, the ideal EROC observer makes use of the
      posterior mean estimator. Other estimators that arise as special cases include
      maximum a posteriori estimators and maximum-likelihood estimators.

PMID- 18059919
TI  - Analysis of observer performance in unknown-location tasks for tomographic image
      reconstruction.
AB  - Our goal is to optimize regularized image reconstruction for emission tomography
      with respect to lesion detectability in the reconstructed images. We consider
      model observers whose decision variable is the maximum value of a local test
      statistic within a search area. Previous approaches have used simulations to
      evaluate the performance of such observers. We propose an alternative approach,
      where approximations of tail probabilities for the maximum of correlated Gaussian
      random fields facilitate analytical evaluation of detection performance. We
      illustrate how these approximations, which are reasonably accurate at low
      probability of false alarm operating points, can be used to optimize
      regularization with respect to lesion detectability.

PMID- 18059920
TI  - Two-frequency radiative transfer: Maxwell equations in random dielectrics.
AB  - The paper addresses the space-frequency correlations of electromagnetic waves in
      general random, bianisotropic media whose constitutive tensors are complex
      Hermitian matrices. The two-frequency Wigner distribution (2f-WD) for polarized
      waves is introduced to describe the space-frequency correlations, and the closed
      form Wigner-Moyal equation is derived from the Maxwell equations. Two-frequency
      radiative transfer (2f-RT) equations are then derived from the Wigner-Moyal
      equation by using the multiple-scale expansion. For the simplest isotropic
      medium, the result coincides with Chandrasekhar's transfer equation. In
      birefringent media, the 2f-RT equations take the scalar form due to the absence
      of depolarization. A number of birefringent media such as chiral, uniaxial, and
      gyrotropic media are examined. For the unpolarized wave in an isotropic medium
      the 2f-RT equations reduces to the 2f-RT equation previously derived in part I of
      this research [J. Opt. Soc. Am. A24, 2248 (2007)]. A similar Fokker-Planck-type
      equation is derived from the scalar 2f-RT equation for the birefringent media.

PMID- 18059921
TI  - Optical constants of Yb films in the 23-1700 eV range.
AB  - The optical constants of Yb films have been determined in the 23-1700 eV spectral
      range from transmittance measurements performed in situ on Yb films deposited by
      evaporation in ultrahigh vacuum conditions. Yb films were deposited over grids
      coated with a thin carbon film. Transmittance measurements were used to obtain
      the extinction coefficient of Yb films at each individual photon energy
      investigated. The energy range investigated encompasses Yb edges from M(4,5) to
      O(2,3). The current results, along with data in the literature, show that Yb has
      an interesting low-absorption band in the approximately 12-24 eV range, which may
      be useful for the development of transmittance filters and multilayer coatings.
      The current data along with literature data and extrapolations were used to
      obtain n, the real part of the complex refractive index, using a Kramers-Kronig
      analysis. The application of the sum rules showed a good consistency of the
      results.

PMID- 18059922
TI  - Characteristic functions of Hartmann-Shack wavefront sensors and laser-ray
      tracing aberrometers.
AB  - It is shown that the aberration estimated at any point of the pupil using
      wavefront slope aberrometers such as Hartmann-Shack wavefront sensors or laser
      ray tracers is a spatial average of the actual aberration weighted by a
      characteristic function that depends on the aberrometer design and on the
      estimation procedure. This characteristic function, whose explicit form is given
      here for wavefront slope aberrometers using either modal or zonal estimators, may
      be useful in analyzing some basic aspects of the aberrometer performance. It is
      also instrumental in establishing the links between the statistical properties of
      the actual and the estimated aberrations. Explicit formulas are given to show in
      terms of this function how the bias arises in the first- and second-order
      statistics of the retrieved aberrations. This approach is mathematically
      equivalent to the analysis of the effects of modal coupling (cross-coupling and
      aliasing). It may provide, however, some complementary insight.

PMID- 18059923
TI  - Inverse problem approach in particle digital holography: out-of-field particle
      detection made possible.
AB  - We propose a microparticle detection scheme in digital holography. In our inverse
      problem approach, we estimate the optimal particles set that best models the
      observed hologram image. Such a method can deal with data that have missing
      pixels. By considering the camera as a truncated version of a wider sensor, it
      becomes possible to detect particles even out of the camera field of view. We
      tested the performance of our algorithm against simulated and experimental data
      for diluted particle conditions. With real data, our algorithm can detect
      particles far from the detector edges in a working area as large as 16 times the
      camera field of view. A study based on simulated data shows that, compared with
      classical methods, our algorithm greatly improves the precision of the estimated
      particle positions and radii. This precision does not depend on the particle's
      size or location (i.e., whether inside or outside the detector field of view).

PMID- 18059924
TI  - Generalized higher-order nonlinear energy operators.
AB  - We extend and generalize the Teager-Kaiser [in Proceedings of IEEE International
      Conference on Acoustics, Speech, and Signal Processing (1993), Vol. 3, p. 149]
      and the higher-order differential energy operators [IEEE Signal Process. Lett.2,
      152 (1995)] to a large class of operators called higher-order energy operators.
      We show that for AM-FM signal demodulation, the introduced partial derivative
      orders have to satisfy certain conditions. These operators are parameterized for
      local processing of AM-FM signals. The operators are illustrated using synthetic
      signals and a real signal from light scanning interferometry.

PMID- 18059925
TI  - Quantitative temporal speckle contrast imaging for tissue mechanics.
AB  - We demonstrate through a series of simulations that by parameterizing the
      temporal speckle contrast statistic from a sequence of translating speckle images
      on a number of experimental constants, the local temporal contrast can be used to
      quantitatively assess local motion, provided that the spatial and temporal
      Nyquist sampling criteria are both met. We develop a simple exponential model for
      quantifying speckle motion for speckle patterns that display arbitrary intensity
      statistics and provide suggestions for optimizing both the experimental
      acquisition of speckle data and the temporal contrast analysis of the data. The
      confounding effects of uncorrelated noise are also discussed. The model is
      demonstrated by applying it to an optical coherence tomography image sequence of
      an engineered tissue construct undergoing dynamic compression. Applications to
      tissue mechanics are shown, although the discussion is equally relevant for fluid
      motion studies.

PMID- 18059926
TI  - Fourier transform profilometry based on a projecting-imaging model.
AB  - In order to obtain the correct height reconstruction of a measured object, a
      projection lens and a camera lens must be placed at equal heights above the
      reference plane in the traditional Fourier transform profilometry (FTP) method.
      We propose an improved phase-height mapping formula based on an improved
      description of the reference fringe and the deformed fringe in FTP when the
      projection lens and the camera lens are not placed at equal height. With our
      method, it is easier to obtain the full-field fringe by moving either the
      projector or the imaging device. In some cases, where the required parallel
      condition cannot be met, the proposed method offers a flexible way to calculate
      the height distribution.

PMID- 18059927
TI  - Optical design of freeform two-mirror beam-shaping systems.
AB  - The problem of design of a two-mirror optical system for reshaping the irradiance
      distribution of a laser beam in a prescribed manner is considered in the
      geometrical optics approximation. The presented design equations are derived in a
      rigorous manner and are applicable to two-mirror optical systems not limited to
      radiance profiles and beam cross sections that are rotational or rectangular
      symmetric. The resulting mirrors are free-form surfaces not restricted by a
      priori constraints. Moreover, the presented approach shows also that even in the
      general case two different designs are available for the same data. In one of
      these designs the first mirror is always concave and the second is convex, while
      in the second design the resulting mirrors may be neither convex nor concave.
      Since, in general, the surface mirrors are aspherical, the availability of a
      design with convex and concave mirrors is particularly important for fabrication.

PMID- 18059928
TI  - Generation of nondiffracting beams through an opaque disk.
AB  - A new method of generating nondiffracting beams is presented. It consists of
      focusing a Gaussian beam in the vicinity of an opaque disk. A beam is generated
      whose central peak is surrounded by a wide number of bright rings (approximately
      250). After collimation, the beam propagates without changing the rings' radii,
      similar to a diffraction-free beam. The central peak can conserve its dimension
      over more than 5 m. The diameter of the central peak is adjusted by choosing the
      focal length of the collimating lens. Experimental results are well predicted by
      our theoretical developments that simulate exactly the paraxial diffraction.

PMID- 18059929
TI  - 4Pi spectral self-interference microscopy.
AB  - Spectral self-interference microscopy (SSM) relies on the balanced collection of
      light traveling two different paths from the sample to the detector, one direct
      and the other indirect from a reflecting substrate. The resulting spectral
      interference effects allow nanometer-scale axial localization of isolated
      emitters. To produce spectral fringes the difference between the two optical
      paths must be significant. Consequently, to ensure that both contributions are in
      focus, a low-numerical-aperture objective lens must be used, giving poor lateral
      resolution. Here this limitation is overcome using a 4Pi apparatus to produce the
      requisite two paths to the detector. The resulting instrument generalizes both
      SSM and 4Pi microscopy and allows a quantification of SSM resolution (rather than
      localization precision). Specifically, SSM is shown to be subject to the same
      resolution constraints as 4Pi microscopy.

PMID- 18059930
TI  - Removal of the Gibbs phenomenon and its application to fast-Fourier-transform
      based mode solvers.
AB  - A simple strategy for accurately recovering discontinuous functions from their
      Fourier series coefficients is presented. The aim of the proposed approach, named
      spectrum splitting (SS), is to remove the Gibbs phenomenon by making use of
      signal-filtering-based concepts and some properties of the Fourier series. While
      the technique can be used in a vast range of situations, it is particularly
      suitable for being incorporated into fast-Fourier-transform-based electromagnetic
      mode solvers (FFT-MSs), which are known to suffer from very poor convergence
      rates when applied to situations where the field distributions are highly
      discontinuous (e.g., silicon-on-insulator photonic wires). The resultant method,
      SS-FFT-MS, is exhaustively tested under the assumption of a simplified one
      dimensional model, clearly showing a dramatic improvement of the convergence
      rates with respect to the original FFT-based methods.

PMID- 18059931
TI  - Modal analysis and suppression of the Fourier modal method instabilities in
      highly conductive gratings.
AB  - The Fourier modal method (FMM), often also referred to as rigorous coupled-wave
      analysis (RCWA), is known to suffer from numerical instabilities when applied to
      low-loss metallic gratings under TM incidence. This problem has so far been
      attributed to the imperfect conditioning of the matrices to be diagonalized. The
      present analysis based on a modal vision reveals that the so-called instabilities
      are true features of the solution of the mathematical problem of a binary metal
      grating dealt with by truncated Fourier representation of Maxwell's equations.
      The extreme sensitivity of this solution to the optogeometrical parameters is the
      result of the excitation, propagation, coupling, interference, and resonance of a
      finite number of very slow propagating spurious modes. An astute management of
      these modes permits a complete and safe removal of the numerical instabilities at
      the price of an arbitrarily small and controllable reduction in accuracy as
      compared with the referenced true-mode method.

PMID- 18059932
TI  - Electro-optical investigations of holographic-polymer-dispersed ferroelectric
      liquid crystals.
AB  - Uniform alignment of ferroelectric liquid-crystal domains encapsulated by a
      polymer binder was established through a holographic exposure process. The
      refractive index modulation in these thin films is modeled as a phase grating
      that can be electrically addressed to erase the optical diffractive properties. A
      phenomenological model is developed to take into account a distribution of domain
      sizes and an effective field that stabilizes the ferroelectric liquid-crystal
      domains. A diffraction model successfully predicts changes in normalized
      intensities for first-order diffraction with applied field. These gratings
      demonstrate microsecond-scale response and relaxation times for various grating
      pitch sizes between approximately 3 and approximately 12 microm.

PMID- 18059933
TI  - Optical constants of electron-beam evaporated boron films in the 6.8-900 eV
      photon energy range.
AB  - The optical constants of electron-beam evaporated boron from 6.8 to 900 eV were
      calculated through transmittance measurements of boron thin films deposited onto
      carbon-coated microgrids or LiF substrates in ultrahigh-vacuum conditions. In the
      low-energy part of the spectrum the measurements were performed in situ on
      freshly deposited samples, whereas in the high-energy range the samples were
      exposed to the atmosphere before the measurements. The extinction coefficient was
      calculated directly from the transmittance data, and a Kramers-Kronig analysis
      that combined the current data with data from the literature was performed to
      determine the dispersive part of the index of refraction. Finally, two different
      sum-rule tests were performed that indicated the good consistency of the data.

PMID- 18059934
TI  - Minimization of geometric-beam broadening in a grating-based time-domain delay
      line for optical coherence tomography application.
AB  - This paper discusses a dispersion effect in a grating-based time-domain delay
      line that is different from the second- or higher-order dispersion in a grating
      based Fourier-domain delay line. When the lateral broadening of the beam profile
      after grating dispersion exceeds the collection aperture of the reference fiber,
      the peripheral spectrum is decoupled by the fiber. The loss of reference spectral
      bandwidth by this geometric-beam broadening thus degrades the axial resolution.
      The polarizing-beam reflector used in the Fourier-domain delay line for
      suppression of lateral beam walk-off is implemented in this grating-based time
      domain delay line to minimize geometric-beam broadening. Theoretical analysis and
      experiments are given to validate the axial resolution improvement after
      geometric-beam broadening is minimized. In vitro and in vivo imaging results are
      presented to demonstrate the improvement. It is also shown that geometric-beam
      broadening may exist in other optical coherence tomography reference arm
      configurations.

PMID- 18059935
TI  - Analysis of blazed diffractive optical elements formed with artificial
      dielectrics.
AB  - A new hybrid method for the analysis of diffractive optical elements, which
      combines fully vectorial and scalar theories, is presented. It is suitable for
      use with elements of arbitrary large zone, even when the local feature size is of
      the order of the wavelength. To assess its applicability, we have performed cross
      checking tests. The model is shown to accurately predict many optical properties
      of diffractive optical elements based on two-dimensional artificial dielectrics,
      like the useful energy diffracted into the order of interest or the deterministic
      loss into high diffraction orders for an illumination with a wavelength different
      from the design wavelength or for highly oblique incidence.

PMID- 18059936
TI  - Open-loop control of a MEMS deformable mirror for large-amplitude wavefront
      control.
AB  - A method is introduced for predicting control voltages that will generate a
      prescribed surface shape on a MEMS deformable mirror. The algorithm is based upon
      an analytical elastic model of the mirror membrane and an empirical
      electromechanical model of its actuators. It is computationally simple and
      inherently fast. Shapes at the limit of achievable mirror spatial frequencies
      with up to 1.5 microm amplitudes have been achieved with less than 15 nm rms
      error.

PMID- 18059937
TI  - Scaling of resonance frequency for strong injection-locked lasers.
AB  - It has been shown that strong optical injection locking can significantly enhance
      the resonance frequency of semiconductor lasers. In this Letter, we describe the
      trade-off between the maximum resonance frequency enhancement and the quality
      factor (Q) of the lossless laser cavity and show that the time-bandwidth product
      (product of photon lifetime and maximum resonance frequency) is equal to one half
      the square root of the external power injection ratio. The theoretical model
      agrees well with our experimental data.

PMID- 18059938
TI  - Design of wavelength tunable long-period grating couplers based on asymmetric
      nonlinear dual-core fibers.
AB  - We demonstrate a grating coupler using an asymmetric nonlinear dual-core fiber
      with a pair of long-period gratings (LPGs). Simple formulas for the achievement
      of 100% coupling efficiency and small sidelobes are derived. The passband
      exhibits steep band transitions. By launching high-intensity optical pumps to
      alter the refractive indices of the fiber cores through cross-phase modulation, a
      wavelength tunable LPG dual-core coupler can be realized.

PMID- 18059939
TI  - Programmable common-path vector field synthesizer for femtosecond pulses.
AB  - We demonstrate a novel design for a femtosecond vector field synthesizer. Pulse
      shaping of all four degrees of freedom of the electric field (amplitude, phase,
      ellipticity, and orientation angle) is achieved with a single 1D double-layer
      spatial light modulator in a zero-dispersion compressor by modulating the
      amplitude and phase of the two transverse polarization components in separate
      halves of the modulator. Being a common-path arrangement, it is
      interferometrically stable and therefore usable for long-term measurements. The
      method can be broadly applied in coherent control and nonlinear spectroscopy.

PMID- 18059940
TI  - Diode-pumped sub-100 fs Kerr-lens mode-locked Yb3+:Sc2O3 ceramic laser.
AB  - Diode-pumped Kerr-lens mode-locked laser operations of Yb3+:Sc2O3 ceramics have
      been achieved. 92 fs pulses with the average power of 850 mW under 3.89 W
      incident pump power were obtained at a center wavelength of 1042 nm. The optical
      to-optical efficiency was 21.9%. 90 fs pulses with the average power of 160 mW
      were also obtained at a center wavelength of 1092 nm. To our knowledge, this is
      the first demonstration of a Kerr-lens mode-locked Yb3+:Sc2O3 laser.

PMID- 18059941
TI  - Bandpass filter with adjustable bandwidth based on a press-induced long-period
      twisted holey-fiber grating.
AB  - A bandpass filter with adjustable bandwidth based on a press-induced long-period
      grating in a twisted holey fiber is presented. By twisting the holey fiber prior
      to the application of periodic pressure, each rejection band of the nontwisted
      induced long-period grating is split into two shifted rejection bands that move
      further apart as the twist ratio increases. This feature results in a wide
      bandpass filter with controllable bandwidth. A bandpass filter at 1523 nm with
      adjustable bandwidth from 15 to 65 nm with near-linear response and insertion
      loss lower than 0.7 dB is demonstrated. Additionally, the bandpass filter can be
      tuned over 100 nm.

PMID- 18059942
TI  - Unequally spaced multiple mid-infrared wavelength generation using an engineered
      quasi-phase-matching device.
AB  - We propose a novel quasi-phase-matched (QPM) device that can generate unequally
      spaced multiple wavelengths. Unequally spaced multiple QPM peaks can be obtained
      by employing the optimized phase modulation of a periodic domain structure. We
      fabricated a LiNbO3 waveguide device for 3.2-3.4 microm band difference frequency
      generation based on the design. Using the multiple mid-infrared outputs, we
      demonstrate the detection of multiple hydrocarbon gases, namely, methane,
      ethylene, and ethane.

PMID- 18059943
TI  - Homodyne fiber optic backscatter dynamic light scattering.
AB  - Optical homodyne detection in the backscatter direction is achieved through a
      pair of collinearly located fibers in a cylindrical probe body. One fiber
      illuminates the scattering solution while the other fiber provides optical mixing
      of the backscattered optical field with a local oscillator derived from the
      Fresnel reflections at the glass interfaces of the sample container. Homodyne
      detection is possible over a broad range of particle size and sample
      concentration with a single probe design.

PMID- 18059944
TI  - Controlling speckle using lenses and free space.
AB  - The correlation properties of speckle fields are studied for general paraxial
      systems. The previous studies on lateral and longitudinal speckle size for the
      case of free-space propagation (Fresnel transform) are generalized to the case of
      the linear canonical transform. These results have implications for the control
      of speckle size, through appropriate design of optical systems, with particular
      relevance for speckle interferometry.

PMID- 18059945
TI  - High-quality lowest-loss-mode lasing in GaAs quasi-stadium laser diodes having
      unstable resonators.
AB  - We obtained high-quality lowest-loss-mode lasing in quasi-stadium laser diodes
      having unstable resonators that consisted of two curved end mirrors and two
      straight sidewall mirrors. The laser diodes were fabricated by applying a
      reactive ion etching technique to a metal-organic chemical-vapor deposition-grown
      graded-index separate-confinement heterostructure single-quantum-well GaAs/AlGaAs
      structure. The electrode contact area of the laser diodes was formed along
      unstable periodic orbits, along which the optical beams are localized. Highly
      directional fan-out beams corresponding to the numerically obtained lowest loss
      mode were emitted from the end mirrors under CW operation at room temperature.

PMID- 18059946
TI  - Polarization invariance in beam propagation.
AB  - It has been known for some time that the degree of polarization of a light beam
      may change on propagation, even in free space. In this Letter we derive
      sufficiency conditions for the degree of polarization of a beam generated by a
      uniformly polarized stochastic, electromagnetic source of a wide class to be the
      same throughout the far zone and in the source plane.

PMID- 18059947
TI  - Design of a high-speed optical dark-soliton detector using a phase-shifted
      waveguide Bragg grating in reflection.
AB  - A theoretical study of a new application of a simple pi-phase-shifted waveguide
      Bragg grating (PSWBG) in reflection mode as a high-speed optical dark-soliton
      detector is presented. The PSWBG consists of two concatenated identical uniform
      waveguide Bragg gratings with a pi phase shift between them. The reflective
      PSWBG, with grating reflectivities equal to 0.9, a free spectral range of 1.91
      THz, and a nonlinear phase response, can convert a 40 Gbit/s noisy dark-soliton
      signal into a high-quality 40 Gbit/s return-to-zero signal with a peak power
      level of approximately 17.5 dB greater than that by the existing Mach-Zehnder
      interferometer with free spectral range of 1.91 THz and a linear phase response.

PMID- 18059948
TI  - Surface plasmon-polariton waveguiding characteristics of metal/dielectric quasi
      coplanar structures.
AB  - A novel metal-dielectric structure for efficient confinement and guiding of
      surface plasmon-polaritons is proposed. The proposed quasi-coplanar geometry
      achieves a trenchlike mode confinement over a wide range of spectrum by
      substituting a trench structure with two patterned metal layers, which will
      simplify the fabrication steps significantly. Using the finite-element method,
      the modal characteristics and the impact of waveguide structural parameters on
      them were investigated.

PMID- 18059949
TI  - Excitation-resolved hyperspectral fluorescence lifetime imaging using a UV
      extended supercontinuum source.
AB  - We present a time-gated, optically sectioned, hyperspectral fluorescence lifetime
      imaging (FLIM) microscope incorporating a tunable supercontinuum excitation
      source extending into the UV. The system is capable of resolving the excitation
      spectrum, emission spectrum, and fluorescence decays in an optically sectioned
      image.

PMID- 18059950
TI  - Direct time-response measurement of high-speed optical modulators based on
      stretched-pulse interferometry.
AB  - A simple technique for the direct measurement of the complex temporal response of
      a high-speed electro-optic (EO) modulator is proposed. This technique recovers
      the amplitude and phase temporal profiles of an instantaneous modulation over the
      duration of a chirped pulse (obtained by linear dispersion) using Fourier
      transform interferometry, and it exploits the time-to-frequency mapping induced
      by the pulse dispersion process. The method can be implemented by using either
      time- or frequency-domain interferometric detection, allowing the
      characterization of modulation bandwidths in the tens-of-gigahertz range. The
      concept is demonstrated by accurately measuring the complex temporal response of
      a 2.5 Gbps intensity EO modulator.

PMID- 18059951
TI  - Polarization-tunable plasmon-enhanced extraordinary transmission through metallic
      films using asymmetric cruciform apertures.
AB  - Plasmon-enhanced transmission of light incident on a periodic array of nanoscale,
      asymmetric cruciform patterns is demonstrated. The corresponding transmission
      spectra are shown to be polarization dependent and possess unique properties,
      such as the existence of isosbestic points for which the transmission is
      polarization insensitive. Transmission peaks corresponding to localized surface
      plasmon resonances and extended surface plasmons are also identified.

PMID- 18059952
TI  - Tight focusing of radially polarized Gaussian and Bessel-Gauss beams.
AB  - We examine the effects of tightly focusing a radially polarized beam with
      uniform, Gaussian, or Bessel-Gauss pupil functions. The resulting FWHM is
      smallest for the case of a uniform amplitude profile, while the Bessel-Gauss beam
      results in the largest FWHM. The uniform amplitude profile also results in an
      axial field component that increases fastest with increasing NA. The ratio of the
      axial component to the transverse component is also the greatest for the uniform
      pupil function. On the other hand, the Bessel-Gauss beam benefits the most from
      the use of an annulus.

PMID- 18059953
TI  - Infrared hollow fiber with a vitreous film as the dielectric inner coating layer.
AB  - A vitreous material with an optimum reflective index of 1.41 for dielectric
      metallic hollow fiber is used for what is believed to be the first time. A smooth
      vitreous film is formed by the treatment of a hardener at room temperature by
      using the liquid-phase coating technique. Low-loss properties were obtained in
      both the infrared and visible wavelength regions, and the fibers are of high
      durability when sterilized. This hollow fiber is promising for use in medical
      applications or other harsh environments.

PMID- 18059954
TI  - Use of a scanner to modulate spatial interferograms for in vivo full-range
      Fourier-domain optical coherence tomography.
AB  - We report a new yet simple method to achieve full-range complex Fourier-domain
      optical coherence tomography (OCT) for in vivo imaging. The method utilizes a
      scanner that is dedicated for lateral scanning in the system to introduce a
      constant carrier frequency into the OCT spectral interferograms during the
      scanning. This is achieved by simply offsetting the sampling beam spot away from
      the pivot point of the scanning mirror. We demonstrate the method experimentally
      for in vivo full-range imaging of the anterior segment of a human eye. The method
      is free from complex conjugate mirror image and self-cross-correlation image
      artifacts.

PMID- 18059955
TI  - Quantitative measurement of timing and phase dynamics in a mode-locked laser.
AB  - We present results of an experimental study of the timing and phase dynamics in a
      mode-locked Ti:sapphire laser. By measuring the response of two widely spaced
      comb lines to a sinusoidal modulation of the pump power, we determine
      quantitatively the response of both the central pulse time and the phase. Because
      of the distinct response of the pulse energy, central frequency, and gain to the
      modulation, we are able to distinguish their contributions to the timing and
      phase dynamics.

PMID- 18059956
TI  - Subpixel smoothing for conductive and dispersive media in the finite-difference
      time-domain method.
AB  - Staircasing of media properties is one of the intrinsic problems of the finite
      difference time-domain method, which reduces its accuracy. There are different
      approaches for solving this problem, and the most successful of them are based on
      correct approximation of inverse permittivity tensor epsilon(-1) at the material
      interface. We report an application of this tensor method for conductive and
      dispersive media. For validation, comparisons with analytical solutions and
      various other subpixel smoothing methods are performed for the Mie scattering
      from a small sphere.

PMID- 18059957
TI  - Impedance-matched hyperlens.
AB  - We propose an approach to optical imaging beyond the diffraction limit, based on
      transformation optics in concentric circular cylinder domains. The resulting
      systems allow image magnification and minimize reflection losses due to the
      impedance matching at the input or output boundaries. While perfect impedance
      matching at both surfaces can be obtained only in a system with radius-dependent
      magnetic permeability, we demonstrate that comparable performance can be achieved
      in an optimized nonmagnetic design.

PMID- 18059958
TI  - Ultrafast optical nonlinearity enhancement in metallodielectric multilayer
      stacks.
AB  - Metal-dielectric multilayer films show high transmission at some specific
      wavelengths of light due to multiple Bragg reflections. By designing the
      multilayer structure, the high transmission position can be tuned to be on
      resonance with the laser wavelength at which the light can penetrate into the
      highly nonlinear metallic layers, leading to an enhanced nonlinear optical
      response. By employing a femtosecond optical Kerr technique, we experimentally
      investigated Ag-TiO2 multilayer stacks, and an enhanced nonlinear optical
      response was observed.

PMID- 18059959
TI  - Miniaturization of Fresnel phase matching using a side-coupled integrated spaced
      sequence of resonators (SCISSOR).
AB  - It is proposed that a side-coupled integrated spaced sequence of resonators
      (SCISSOR) be used to adapt Fresnel phase matching to the case of highly confining
      waveguides. As is the case for bulk media, this method of quasi-phase-matching
      (QPM) allows resonant or nonresonant QPM. This property can be used to control
      the spectral bandwidth of the phase-matching curve.

PMID- 18059960
TI  - Mystery of the double limit in homogenization of finitely or perfectly conducting
      periodic structures.
AB  - We show that the difference in the effective medium properties of perfectly or
      finitely conducting short-period gratings is because for finitely conducting
      gratings it is possible to completely homogenize the electromagnetic field vector
      components, contrary to perfectly conducting gratings. As a consequence, for
      aluminum in the microwave domain, two possible effective media can be found,
      depending on whether the feature dimensions are much larger or shorter than the
      depth of field penetration inside the metal.

PMID- 18059961
TI  - White light emission from blue and near ultraviolet light-emitting diodes
      precoated with a Sr3SiO5:Ce3+,Li+ phosphor.
AB  - White-light-emitting diodes (WLEDs) were fabricated by combining a yellow
      Sr3SiO5:Ce3+, Li+ phosphor with a blue light-emitting diode (LED) (460 nm chip)
      or a near ultraviolet (n-UV) LED (405 nm chip), respectively. Color temperature
      (Tc) of Sr3SiO5:Ce3+, Li+-based WLEDs could be tuned from 6500 to 100,000 K (blue
      LED pumping) and from 4900 to 50,000 K (n-UV LED pumping) without mixing with
      other phosphors. The blue LED-pumped WLED showed excellent white light (luminous
      efficiency=31.7 lm/W, Tc=6857 K) at 20 mA. This WLED showed a stable color
      coordinates property against an increase of the forward current. An n-UV LED
      pumped WLED also showed bright white light (25.0 lm/W, 5784 K) at 20 mA.

PMID- 18059962
TI  - Purkinje imaging system to measure anterior segment scattering in the human eye.
AB  - We present an instrument based on Purkinje imaging that permits the objective
      measurement of the amount of scattering associated with the eye's anterior
      segment, avoiding the contribution from the retina. The experimental system
      records the fourth Purkinje image, and adequate processing is used to compute a
      parameter that quantifies the scattering. The method was first tested in an
      artificial eye and later in normal young eyes wearing customized contact lenses
      that induced different amounts of scatter. We were able to detect scattering
      increments, which indicates that this technique may be used as an objective tool
      to quantify the level of scattering in the anterior segment of the living human
      eye. The future use of this technique in clinical environments might help to
      estimate the level of corneal haze in eyes undergoing refractive surgery or/and
      scattering within the lens during cataract development.

PMID- 18059963
TI  - Retinal flow cytometer.
AB  - The in vivo flow cytometer is an instrument capable of continuous, real-time
      monitoring of fluorescently labeled cells in the circulation without the need to
      draw blood samples. However, the original system probes a single vessel in the
      mouse ear; the small sample volume limits the sensitivity of the technique. We
      describe an in vivo retinal flow cytometer that simultaneously probes five artery
      vein pairs in the mouse eye by circularly scanning a small laser spot rapidly
      around the optic nerve head. We demonstrate that the retinal flow cytometer
      detects about five times more cells per minute than the original in vivo flow
      cytometer does in the ear.

PMID- 18059964
TI  - Complex ambiguity-free Fourier domain optical coherence tomography through
      transverse scanning.
AB  - We introduce a simple and cheap method for phase-shifting Fourier domain optical
      coherence tomography (FDOCT) that does not need additional devices and can easily
      be implemented. A small beam offset at the fast beam-scanning mirror introduces a
      causal phase shift, which can be used for B-scan-based complex image
      reconstruction. We derive the conditions for optimal conjugate suppression and
      demonstrate the method on human skin in vivo for spectrometer-based FDOCT
      operating at 1300 nm employing a handheld scanner.

PMID- 18059965
TI  - Full-field and real-time surface plasmon resonance imaging thermometry.
AB  - The feasibility of surface plasmon resonance (SPR) imaging thermometry is tested
      as a potential tool for full-field and real-time temperature field mapping for
      thermally transient liquid mediums. Using the well-known Kretschmann's analysis
      [Physik 241, 313 (1971)]. parametric examinations are performed to delineate the
      effects of important optical properties, including seven different prism
      materials with different refractive index values and seven different measured
      dielectric constants for thin gold (Au) films (approximately 47.5 nm in
      thickness), on the temperature dependence of SPR reflectance intensity
      variations. Furthermore, a laboratory-implemented real-time SPR thermometry
      system demonstrates the full-field mapping capabilities for transient temperature
      field developments in the near-wall region when a hot water droplet (80 degrees
      C) contacts the Au metal surface (20 degrees C) and spreads either in an air- or
      in a water-surrounded environment.

PMID- 18059966
TI  - Cartesian beams.
AB  - A new and very general beam solution of the paraxial wave equation in Cartesian
      coordinates is presented. We call such a field a Cartesian beam. The complex
      amplitude of the Cartesian beams is described by either the parabolic cylinder
      functions or the confluent hypergeometric functions, and the beams are
      characterized by three parameters that are complex in the most general situation.
      The propagation through complex ABCD optical systems and the conditions for
      square integration are studied in detail. Applying the general expression of the
      Cartesian beams, we also derive two new and meaningful beam structures that, to
      our knowledge, have not yet been reported in the literature. Special cases of the
      Cartesian beams are the standard, elegant, and generalized Hermite-Gauss beams,
      the cosine-Gauss beams, the Lorentz beams, and the fractional order beams.

PMID- 18059967
TI  - Acceleration in vacuum of bare nuclei by tightly focused radially polarized laser
      light.
AB  - Fields of a radially polarized petawatt laser beam, represented by a truncated
      series in the diffraction angle epsilon to order epsilon15 and focused to
      subwavelength waist radius, are shown to accelerate protons and bare nuclei to
      several hundred MeV per nucleon over a distance equivalent to a few laser
      wavelengths.

PMID- 18059968
TI  - Signal spatial filtering for co-phasing in seeing-limited conditions.
AB  - We present the results of the co-phasing closed loop performed with a pyramid
      wavefront sensor for what we believe to be the first time in the presence of
      emulated atmospheric disturbance. The performance of the co-phasing loop is
      significantly improved by applying two spatial filters in the sensor signal
      space. The first is a zonal filter applied to the interaction matrix before the
      computation of the reconstructor; the second is a modal filter applied to the
      sensor signals before the correction command computation. The presented
      laboratory results demonstrate that, applying both filters, the time requested to
      average out the atmospheric disturbance in each loop step is reduced by 2 orders
      of magnitude, improving the loop stability and accuracy.

PMID- 18059969
TI  - Comment on "Wide-field coherent anti-Stokes Raman scattering microscopy with non
      phase-matching illumination".
AB  - We comment on a Letter by Toytman et al. [Opt. Lett.32, 1941 (2007)] in which a
      novel setup for wide-field imaging in coherent anti-Stokes Raman scattering
      (CARS) microscopy is demonstrated. There the authors state that our phase
      matching implementation of a wide-field CARS system [Appl. Phys. Lett.84, 816
      (2004); New J. Phys.8, 36 (2006)] suffers from a strong background from the bulk
      medium. However, our results show quite the contrary, i.e., that our setup
      provides a very good signal contrast, due to an almost vanishing background level
      from the bulk solvent.

PMID- 18059971
TI  - Coherent anti-Stokes Raman scattering microspectroscopy of silicon components
      with a photonic-crystal fiber frequency shifter.
AB  - Coherent anti-Stokes Raman scattering (CARS) microspectroscopy of silicon
      components is demonstrated with pump and probe fields delivered by a mode-locked
      Cr:forsterite laser and the frequency-shifted soliton output of a photonic
      crystal fiber as a Stokes field. CARS microspectroscopy is shown to allow a
      visualization of microscale features and defects on the surface of silicon
      wafers, offering much promise for online diagnostics of electronic and photonic
      silicon chip components.

PMID- 18059972
TI  - Involvement of copper in female reproduction.
AB  - Copper (Cu) is one of the essential trace metals which are necessary in
      maintaining the functioning of living organisms. The current knowledge on the
      role of copper in animal reproduction is presented in the article. Our studies
      have shown that complexes of copper (Cu2+) with gonadotropin-releasing hormone
      (GnRH) are even more effective in the release of LH than native GnRH. Moreover,
      Cu-GnRH is more potent in inducing in vivo release of FSH than LH. Copper
      complexes with GnRH interact with GnRH receptors (GnRHR) and modulate
      intracellular signaling in the gonadotrope cells of the anterior pituitary.
      Copper plays also a significant role in maintaining normal fetus development in
      mammals.

PMID- 18059973
TI  - Melatonin protects against experimental immune ovarian failure in mice.
AB  - Experimental immune ovarian failure induced in CBA mice by either administration
      of xenogenic anti-ovarian antibodies or immunization with allogenic ovarian
      extracts impaired the meiotic maturation of oocytes and increased apoptosis of
      follicular cells. Immunization was accompanied with the inflammation and active
      immune reaction, as shown by the enlargement of regional lymph nodes, the
      increase of apoptosis in cultured lymph node cells and the increase of band and
      segmented neutrophil percentage in the blood. Triple injections of melatonin (5
      mg/kg of the body weight) an hour before antibodies administration restored the
      meiotic maturation of oocytes and supported the survival of follicular and lymph
      node cells. In contrast, melatonin application upon immunization was not
      effective to prevent the ovary impairment and cell death. It is concluded that
      melatonin protects against immune ovary failure induced by xenogenic anti-ovarian
      antibodies.

PMID- 18059974
TI  - Characteristics of sperm motility in boar semen diluted in different extenders
      and stored for seven days at 18 degrees C.
AB  - Although numerous extenders exist for diluting boar semen, little research has
      been conducted comparing commercial extenders with regard to maintaining sperm
      motility during storage. The objective was to use a computer- assisted sperm
      analysis system to assess motility of boar spermatozoa diluted in Beltsville
      Thawing Solution, Merck-III, Androhep-lite, Sperm Aid, MR-A, Modena, X-Cell, VSP,
      and Vital. Ejaculates from boars (n=10) were collected and sub-samples were
      diluted (35x10(6) spermatozoa/ml) in the different extenders and stored for seven
      days at 18 degrees. Extender by day interactions were detected (p<0.01) and on
      each day post collection, there were numerically small, but statistically
      significant differences in characteristics of sperm motility among extenders. For
      example, on day 7, the percentages of motile and progressively motile spermatozoa
      were highest (p<0.05) in X-Cell (90.7%) and Modena (63.9%), respectively. The
      average velocity measured over the actual point-to-point track followed by the
      sperm cell (VCL; 198.2 microm/s) and path velocity of the smoothed cell path
      (VAP; 106.4 microm/s) were highest (p<0.05) in Vital and Modena, respectively.
      Average velocity measured in a straight line from the beginning to the end of the
      track (VSL; 78.3 microm/s), average value of the ratio VSL/VAP (straightness;
      73.2) and average value of the ratio VSL/VCL (linearity; 44.1) on day 7 were
      highest in Androhep-lite. In summary, changes in sperm motility during storage
      were affected by the extender utilized, but with the exception of Sperm Aid, all
      extenders maintained a high degree of sperm motility through 7 days of storage.

PMID- 18059975
TI  - Genistein-induced pituitary prolactin gene expression and prolactin release in
      ovariectomized ewes following a series of intracerebroventricular infusions.
AB  - The aim of the study was to evaluate whether genistein, a phytoestrogen commonly
      present in feed plants, affects prolactin release and its gene expression in the
      pituitary gland. In the experimental model, genistein was infused into the third
      ventricle (IIIv) of the brain in ewes during the short-daylight period (November
      December), when the physiological plasma level of prolactin is low. Animals were
      ovariectomized six weeks before the experiment, to remove the main source of
      endogenous estrogens, and three weeks later a stainless steel guide cannula was
      implanted into IIIv. Genistein (10 ng/100 microl/h, n=5) or vehicle (control,
      n=5) were infused in a series of four one-hour infusions at 30-min intervals
      (from 16:30 to 22:00). Plasma samples were collected at 15-min intervals from
      14:00 to 22:00 through a catheter inserted into the jugular vein and after the
      experiment ewes were slaughtered. Northern blot analysis revealed that pituitary
      prolactin mRNA content increased significantly in response to genistein, compared
      to the vehicle-infused ewes (p<0.05). Prolactin concentration in plasma rose
      significantly during the periods of genistein infusion, as compared to the values
      found before infusion (p<0.05-p<0.01) as well as to the values of the concomitant
      periods in vehicle-infused ewes (p<0.001). Our results show an effective
      estrogenic action of genistein on prolactin synthesis and release in
      ovariectomized ewes that might in part be exerted at the central nervous system
      level.

PMID- 18059976
TI  - The effect of gabapentin and phenytoin on sperm-morphology in Wistar rats.
AB  - The objective of the present study was to investigate the effects of the
      antiepileptic drugs, gabapentin and phenytoin, on sperm morphology in Wistar
      rats. Groups (n=5) of rats were treated with cyclophosphamide (20 mg/day),
      gabapentin (16, 25, 32 mg/day) and phenytoin (3.5, 5.5, 7 mg/day) for five
      consecutive days. 14 and 35 days after the last exposure, sperm morphology was
      evaluated by standard procedure. Gabapentin and phenytoin did not induce
      significant changes in sperm morphology. The results suggest that phenytoin and
      gabapentin are not germ cell mutagens in males, and do not appear to adversely
      affect male fertility.

PMID- 18059977
TI  - Predicting the Length of Stay of Patients Admitted for Intensive Care Using a
      First Step Analysis.
AB  - For patients admitted to intensive care units (ICU), the length of stay in
      different destinations after the first day of ICU admission, has not been
      systematically studied. We aimed to estimate the average length of stay (LOS) of
      such patients in Colombia, using a discrete time Markov process. We used the
      maximum likelihood method and Markov chain modeling to estimate the average LOS
      in the ICU and at each destination after discharge from intensive care. Six
      Markov models were estimated, describing the LOS in each one of the
      Cardiovascular, Neurological, Respiratory, Gastrointestinal, Trauma and Other
      diagnostic groups from the ultimate primary reason for admission to ICU. Possible
      destinations were: the intensive care unit, ward in the same hospital, the high
      dependency unit/intermediate care area in the same hospital, ward in other
      hospital, intensive care unit in other hospital, other hospital, other location
      same hospital, discharge from same hospital and death. The stationary property
      was tested and using a split-sample analysis, we provide indirect evidence about
      the appropriateness of the Markov property. It is not possible to use a unique
      Markov chain model for each diagnostic group. The length of stay varies across
      the ultimate primary reason for admission to intensive care. Although our Markov
      models shown to be predictive, the fact that current available statistical
      methods do not allow us to verify the Markov property test is a limitation.
      Clinicians may be able to provide information about the hospital LOS by
      diagnostic groups for different hospital destinations.

PMID- 18059985
TI  - "These old bones"--a growing public health problem.

PMID- 18059979
TI  - Inflammation and Spinal Cord Injury: Infiltrating Leukocytes as Determinants of
      Injury and Repair Processes.
AB  - The immune response that accompanies spinal cord injury contributes to both
      injury and reparative processes. It is this duality that is the focus of this
      review. Here we consider the complex cellular and molecular immune responses that
      lead to the infiltration of leukocytes and glial activation, promote oxidative
      stress and tissue damage, influence wound healing, and subsequently modulate
      locomotor recovery. Immunomodulatory strategies to improve outcomes are gaining
      momentum as ongoing research carefully dissects those pathways, which likely
      mediate cell injury from those, which favor recovery processes. Current
      therapeutic strategies address divergent approaches including early
      immunoblockade and vaccination with immune cells to prevent early tissue damage
      and support a wound-healing environment that favors plasticity. Despite these
      advances, there remain basic questions regarding how inflammatory cells interact
      in the injured spinal cord. Such questions likely arise as a result of our
      limited understanding of immune cell/neural interactions in a dynamic environment
      that culminates in progressive cell injury, demyelination, and regenerative
      failure.

PMID- 18059986
TI  - Are room temperature and thermal neutral synonymous terms? An investigation of
      common therapeutic modality control variables.
AB  - CONTEXT: Therapeutic modality control variables are thought to be thermal
      neutral, a term sometimes used interchangeably with room temperature. We question
      this common assumption. OBJECTIVE: To determine thermal neutrality of common
      therapeutic modality control variables. DESIGN: We performed 5 laboratory
      experiments, including (1) water temperature over 3 weeks in 3 different
      containers (glass, plastic, and polystyrene); (2) water temperature and volume of
      4 beakers (2 insulated, 2 uninsulated) over 4 weeks, with 1 beaker of each type
      covered by polyethylene; and skin interface temperature of (3) a dry, nonheated
      hydrocollator pack held against the chest, (4) kitty litter applied to the knee,
      and (5) room-temperature ultrasound gel to the forearm. SETTING: Therapeutic
      modalities laboratory. PATIENTS OR OTHER PARTICIPANTS: College student volunteers
      were subjects in experiments 3, 4, and 5. MAIN OUTCOME MEASURE(S): We measured
      temperature and volume change. Data were evaluated using descriptive and
      interferential statistics. RESULTS: Water temperature plateaued significantly
      below room temperature. Temperatures significantly increased in all but the open,
      insulated container. Open containers plateaued at approximately 2 degrees C below
      room temperature and lost significant amounts of water; closed containers
      plateaued at room temperature with negligible water loss. In experiments 3
      through 5, skin temperatures rose significantly during hydrocollator pack, kitty
      litter, and ultrasound gel application. CONCLUSIONS: Room-temperature water
      baths, dry hydrocollator packs, kitty litter, and ultrasound gel were not
      thermally neutral. Room temperature should not be used synonymously with thermal
      neutral. Care must be taken to ensure that control variables truly are
      controlled.

PMID- 18059988
TI  - Cooling efficiency of 4 common cryotherapeutic agents.
AB  - CONTEXT: Cryotherapy is the application of cold as a treatment. It is widely used
      and accepted as beneficial in early management of soft tissue injury. However,
      the most efficient cryotherapeutic agent remains unknown. OBJECTIVE: To compare 4
      common cryotherapeutic agents including crushed ice (CI), gel pack (GP), frozen
      peas (FP), and ice-water immersion (WI) and to determine which agent provided the
      greatest cooling efficiency after a 20-minute application. DESIGN: Repeated
      measures design. SETTING: University physiology laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Nine healthy volunteers participated (5 males, 4 females; age =
      24.0 +/- 4.6 years, height = 1.73 +/- 0.24 m, mass = 79.9 +/- 24.1 kg).
      INTERVENTION(S): The CI, GP, FP, and WI were applied to the right ankle for 20
      minutes. Participants were required to attend 1 measurement session for each
      agent. MAIN OUTCOME MEASURE(S): We recorded skin surface temperature of the right
      ankle at a sampling rate of 1 image/min, using a thermal imaging camera during a
      30-minute rewarming period. RESULTS: Application of CI produced a significantly
      greater reduction in skin surface temperature (19.56 +/- 3.78 degrees C) than GP
      (13.19 +/- 5.07 degrees C) and FP (14.59 +/- 4.22 degrees C) ( P < .001). The CI
      and WI demonstrated significantly ( P < .001) greater cooling efficiency than GP
      and FP. CONCLUSIONS: The CI and WI had the greatest cooling efficiency and
      sustained decreased skin surface temperatures postapplication, indicating these
      agents are potentially the most clinically beneficial.

PMID- 18059978
TI  - Potentiation of Excitotoxicity in HIV-1 Associated Dementia and the Significance
      of Glutaminase.
AB  - HIV-1 Associated Dementia (HAD) is a significant consequence of HIV infection.
      Although multiple inflammatory factors contribute to this chronic, progressive
      dementia, excitotoxic damage appears to be an underlying mechanism in the
      neurodegenerative process. Excitotoxicity is a cumulative effect of multiple
      processes occurring in the CNS during HAD. The overstimulation of glutamate
      receptors, an increased vulnerability of neurons, and disrupted astrocyte support
      each potentiate excitotoxic damage to neurons. Recent evidence suggests that
      poorly controlled generation of glutamate by phosphate-activated glutaminase may
      contribute to the neurotoxic state typical of HAD as well as other
      neurodegenerative disorders. Glutaminase converts glutamine, a widely available
      substrate throughout the CNS to glutamate. Inflammatory conditions may
      precipitate unregulated activity of glutaminase, a potentially important
      mechanism in HAD pathogenesis.

PMID- 18059987
TI  - Validity of devices that assess body temperature during outdoor exercise in the
      heat.
AB  - CONTEXT: Rectal temperature is recommended by the National Athletic Trainers'
      Association as the criterion standard for recognizing exertional heat stroke, but
      other body sites commonly are used to measure temperature. Few authors have
      assessed the validity of the thermometers that measure body temperature at these
      sites in athletic settings. OBJECTIVE: To assess the validity of commonly used
      temperature devices at various body sites during outdoor exercise in the heat.
      DESIGN: Observational field study. SETTING: Outdoor athletic facilities. PATIENTS
      OR OTHER PARTICIPANTS: Fifteen men and 10 women (age = 26.5 +/- 5.3 years, height
      = 174.3 +/- 11.1 cm, mass = 72.73 +/- 15.95 kg, body fat = 16.2 +/- 5.5%).
      INTERVENTION(S): We simultaneously tested inexpensive and expensive devices
      orally and in the axillary region, along with measures of aural,
      gastrointestinal, forehead, temporal, and rectal temperatures. Temporal
      temperature was measured according to the instruction manual and a modified
      method observed in medical tents at local road races. We also measured forehead
      temperatures directly on the athletic field (other measures occurred in a covered
      pavilion) where solar radiation was greater. Rectal temperature was the criterion
      standard used to assess the validity of all other devices. Subjects' temperatures
      were measured before exercise, every 60 minutes during 180 minutes of exercise,
      and every 20 minutes for 60 minutes of postexercise recovery. Temperature devices
      were considered invalid if the mean bias (average difference between rectal
      temperature and device temperature) was greater than +/-0.27 degrees C (+/-0.5
      degrees F). MAIN OUTCOME MEASURE(S): Temperature from each device at each site
      and time point. RESULTS: Mean bias for the following temperatures was greater
      than the allowed limit of +/-0.27 degrees C (+/-0.5 degrees F): temperature
      obtained via expensive oral device (-1.20 degrees C [-2.17 degrees F]),
      inexpensive oral device (-1.67 degrees C [-3.00 degrees F]), expensive axillary
      device (-2.58 degrees C [-4.65 degrees F]), inexpensive axillary device (-2.07
      degrees C [-3.73 degrees F]), aural method (-1.00 degrees C [-1.80 degrees F]),
      temporal method according to instruction manual (-1.46 degrees C [-2.64 degrees
      F]), modified temporal method (-1.36 degrees C [-2.44 degrees F]), and forehead
      temperature on the athletic field (0.60 degrees C [1.08 degrees F]). Mean bias
      for gastrointestinal temperature (-0.19 degrees C [-0.34 degrees F]) and forehead
      temperature in the pavillion (-0.14 degrees C [-0.25 degrees F]) was less than
      the allowed limit of +/-0.27 degrees C (+/-0.5 degrees F). Forehead temperature
      depended on the setting in which it was measured and showed greater variation
      than other temperatures. CONCLUSIONS: Compared with rectal temperature (the
      criterion standard), gastrointestinal temperature was the only measurement that
      accurately assessed core body temperature. Oral, axillary, aural, temporal, and
      field forehead temperatures were significantly different from rectal temperature
      and, therefore, are considered invalid for assessing hyperthermia in individuals
      exercising outdoors in the heat.

PMID- 18059989
TI  - Phonophoresis and the absorption of dexamethasone in the presence of an occlusive
      dressing.
AB  - CONTEXT: Phonophoresis is purported to represent a method to apply topical
      medications through the skin to treat soft tissue injuries and inflammatory
      conditions. Few data are available to demonstrate the clinical effectiveness of
      the treatment. OBJECTIVE: To determine the effect of ultrasound on the
      transcutaneous absorption of dexamethasone when occluded with a dressing. DESIGN:
      Crossover design. SETTING: University general clinical research center. PATIENTS
      OR OTHER PARTICIPANTS: Ten healthy subjects (age = 29.2 +/- 8.8 years; height =
      170.0 +/- 3.9 cm; mass = 67.5 +/- 18.4 kg). INTERVENTION(S): Two grams of 0.33%
      dexamethasone cream were applied to a 10-cm (2) area on the anterior forearm. The
      drug was applied to the skin and occluded with a dressing for 30 minutes before
      the ultrasound and sham ultrasound treatments. The treatments were applied over
      the drug and occlusive dressing. Ultrasound treatments were delivered at an
      intensity of 1.0 W/cm (2) (50% pulsed) at an output frequency of 3 MHz for 5
      minutes and compared with sham ultrasound treatments that were delivered at an
      intensity of 0.0 W/cm (2) (50% pulsed) at an output frequency of 3 MHz for 5
      minutes. All subjects received both the ultrasound and sham treatments, and the
      order in which subjects received the treatments was counterbalanced. MAIN OUTCOME
      MEASURE(S): Serum samples were drawn before treatment and immediately
      posttreatment and at 2, 4, 6, 8, and 10 hours posttreatment. Using high
      performance liquid chromatography, we analyzed serum to determine dexamethasone
      concentrations. RESULTS: A 2-way repeated-measures analysis of variance
      (condition x time) revealed a significant main effect for ultrasound treatment (
      P = .047). The rate of appearance and the total concentration of dexamethasone in
      the serum were greater in subjects after phonophoresis than after sham
      ultrasound. The sham group had only trace amounts of dexamethasone in the serum,
      indicating that drug absorption was negligible without the ultrasound energy. The
      effect size of the phonophoresis condition fell within a 95% confidence interval
      after the baseline measurement. CONCLUSIONS: We found that a phonophoretic effect
      occurred with dexamethasone when its application saturated the skin.

PMID- 18059990
TI  - Arthrogenic muscle response of the quadriceps and hamstrings with chronic ankle
      instability.
AB  - CONTEXT: An arthrogenic muscle response (AMR) of the soleus and peroneal muscles
      has been previously demonstrated in individuals with chronic ankle instability
      (CAI), but the presence of AMR in muscles acting on joints proximal to unstable
      ankles has not been previously explored. OBJECTIVE: To determine if AMR is
      present in the quadriceps and hamstrings muscles of those with and without
      unilateral CAI. DESIGN: Case control. SETTING: University research laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Twenty subjects with unilateral CAI (12 males, 8
      females: age = 19.9 +/- 3.7 years; height = 170.3 +/- 15.6 cm; mass = 78.0 +/-
      23.1 kg) and 21 controls (16 males, 5 females: age = 23.2 +/- 5.4 years; height =
      173.9 +/- 12.7 cm; mass = 87.2 +/- 24.6 kg) with no previous ankle injuries. MAIN
      OUTCOME MEASURE(S): The central activation ratio (CAR), a measure of motoneuron
      pool excitability during maximal voluntary isometric contraction, for the
      hamstrings and quadriceps muscles was measured in both limbs using the
      superimposed burst technique. RESULTS: The CAI group demonstrated quadriceps CARs
      that were significantly larger in their involved limbs (.87 +/- .09), as compared
      with their uninvolved limbs (.84 +/- .08), whereas no significant side-to-side
      difference was seen in the control group (sham involved = .80 +/- .11, sham
      uninvolved = .81 +/- .11). When values from both the involved and uninvolved
      limbs were averaged, the hamstrings CAR was significantly lower for the CAI group
      (.94 +/- .03) than for the control group (.96 +/- .03). CONCLUSIONS: Arthrogenic
      inhibition of the hamstrings muscles bilaterally and facilitation of the
      quadriceps muscle ipsilateral to the involved limb were noted in subjects with
      unilateral CAI. Motoneuron pool excitability appears to be altered in muscles
      that act on joints proximal to the ankle in those with unilateral CAI.

PMID- 18059991
TI  - Correlations among multiple measures of functional and mechanical instability in
      subjects with chronic ankle instability.
AB  - CONTEXT: Although dozens of individual mechanical and functional insufficiencies
      have been reported in those with chronic ankle instability (CAI), no authors to
      date have examined the relationship of the insufficiencies to each other.
      Therefore, studying both the functional and mechanical insufficiencies in the
      same experimental design will provide valuable information. OBJECTIVE: To
      determine the relationships among the numerous functional and mechanical
      insufficiencies purported to cause CAI. DESIGN: Descriptive study with a
      correlational design. SETTING: Medical center and research laboratory. PATIENTS
      OR OTHER PARTICIPANTS: Thirty subjects with unilateral CAI (15 males and 15
      females: age = 20.3 +/- 1.3 years; height = 172.5 +/- 10.7 cm; mass = 72.9 +/-
      15.8 kg). MAIN OUTCOME MEASURE(S): Twenty-six measures of mechanical
      insufficiencies (ankle laxity and hypomobility) and functional insufficiencies
      (subjective level of function, static and dynamic balance, ankle and hip
      strength) were taken on both limbs of all subjects. Bivariate correlations using
      Pearson product moment coefficients were calculated between all dependent
      variables measured in the unstable ankles. The level of significance was set a
      priori at P < or = .05 for all analyses. RESULTS: A number (35) of significant
      bivariate correlations were identified. Most (32) of these significant
      relationships were found between functional instability measures ( r = .38 to
      .96). Three significant relationships were noted between measures of functional
      (balance, strength) and mechanical (laxity, hypomobility) instability ( r = .47
      to .52). No significant relationships were found between the different mechanical
      instability measures. CONCLUSIONS: Certain measures of functional instability
      were significantly correlated and may be redundant. Additionally, the significant
      correlations between measures of functional (balance, strength) and mechanical
      instability (laxity, hypomobility) demonstrate that the 2 factors are not
      completely dichotomous and need to be examined together.

PMID- 18059992
TI  - Balance deficits in recreational athletes with chronic ankle instability.
AB  - CONTEXT: Deficits in static and dynamic stability during single-leg stance have
      been noted in individuals with chronic ankle instability (CAI), but few
      investigators have tested subjects for subtle deficits in dynamic balance. Subtle
      deficits in dynamic balance during a double-leg stance may reveal changes in the
      sensorimotor system because of CAI. OBJECTIVE: To use a standardized tibial nerve
      stimulation as a perturbation to test for dynamic balance deficits between a
      group of recreational athletes with CAI and a group of recreational athletes with
      stable ankles. DESIGN: Case-control study. SETTING: Laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Twenty recreational athletes with CAI and 20 recreational athletes
      with stable ankles. INTERVENTION(S): Balance deficits were assessed for each
      subject during static and dynamic trials. MAIN OUTCOME MEASURE(S): Time to
      stabilization and center-of-pressure excursion path length, velocity, and area
      from ground reaction forces during double-leg stance were collected through a
      forceplate. We used an accelerometer to measure tibial acceleration. Data were
      collected during static stance and during a bilateral perturbation using maximal
      motor neuron recruitment elicited by electric stimulation of the tibial nerve.
      RESULTS: Only time to stabilization in the anterior-posterior direction was
      significantly different between groups ( P = .04), with the CAI group taking
      longer to return to a stable range of ground reaction forces. We found no other
      differences in stability measures between the groups. CONCLUSIONS: Dynamic
      balance in double-leg stance as measured by time to stabilization appears to be
      affected in individuals with CAI. Deficits in the response to external
      perturbation may indicate subtle central sensorimotor changes.

PMID- 18059993
TI  - Plantar foot pressures after the augmented low dye taping technique.
AB  - CONTEXT: Taping and orthoses are frequently applied to control excessive foot
      pronation to treat or prevent musculoskeletal pain and injury of the lower limb.
      The mechanism(s) by which these devices bring about their clinical effects are at
      best speculative and require systematic evaluation. OBJECTIVE: To determine the
      initial effect of the augmented low Dye taping technique (ALD) on plantar foot
      pressures during walking and jogging. DESIGN: Within-subjects, repeated-measures
      randomized control trial. SETTING: Gait research laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Fifteen women and 7 men with an average age of 28.0 +/- 7.4 years
      who were asymptomatic. INTERVENTION(S): Participants walked and jogged along a 12
      m walkway before and after the application of ALD. The untaped side served as the
      control. MAIN OUTCOME MEASURE(S): Peak and mean maximum plantar pressure data
      were calculated for the medial and lateral areas of the rear and midfoot and the
      medial, central, and lateral forefoot areas. Thus, a 3-factor model was tested:
      condition (ALD, control) x time (preapplication, postapplication) x area (medial
      and lateral rearfoot and midfoot and medial, central, and lateral forefoot).
      RESULTS: Significant 3-way interactions were present for both peak and mean
      maximum plantar pressure during walking (F (6,126) = 9.55, P = .006 and F (6,126)
      = 11.36, P = .003, respectively) and jogging (F (6,126) = 5.76, P = .026 and F
      (6,126) = 4.56, P = .045, respectively) tasks. The ALD predominantly increased
      plantar pressures in the lateral midfoot during walking and jogging. In addition,
      tape reduced mean maximum pressure at the medial forefoot and at the medial
      rearfoot during walking. CONCLUSIONS: The ALD, which has previously been shown to
      reduce excessive pronation, produced significant increases in lateral midfoot
      plantar pressures, thereby providing additional information to be considered when
      the mechanism(s) of action of such a treatment are modeled.

PMID- 18059994
TI  - Ankle injuries among United States high school sports athletes, 2005-2006.
AB  - CONTEXT: Ankle injuries are the most common sport-related injuries. To date, no
      studies have been published that use national data to present a cross-sport,
      cross-sex analysis of ankle injuries among US high school athletes. OBJECTIVE: To
      investigate the incidence rates of ankle injuries by sex, type of exposure, and
      sport. DESIGN: Descriptive epidemiologic study. SETTING: One hundred US high
      schools. PATIENTS OR OTHER PARTICIPANTS: United States high school athletes. MAIN
      OUTCOME MEASURE(S): We reviewed ankle injury data collected over the 2005-2006
      school year from a nationally representative sample obtained by High School RIO,
      an injury surveillance system. Specific sports studied were boys' football, boys'
      and girls' soccer, girls' volleyball, boys' and girls' basketball, boys'
      wrestling, boys' baseball, and girls' softball. RESULTS: An estimated 326 396
      ankle injuries occurred nationally in 2005-2006, yielding an injury rate of 5.23
      ankle injuries per 10 000 athlete-exposures. Ankle injuries occurred at a
      significantly higher rate during competition (9.35 per 10 000 athlete-exposures)
      than during practice (3.63) (risk ratio = 2.58; 95% confidence interval = 2.26,
      2.94; P < .001). Boys' basketball had the highest rate of ankle injury (7.74 per
      10 000 athlete-exposures), followed by girls' basketball (6.93) and boys'
      football (6.52). In all sports except girls' volleyball, rates of ankle injury
      were higher in competition than in practice. Overall, most ankle injuries were
      diagnosed as ligament sprains with incomplete tears (83.4%). Ankle injuries most
      commonly caused athletes to miss less than 7 days of activity (51.7%), followed
      by 7 to 21 days of activity loss (33.9%) and more than 22 days of activity loss
      (10.5%). CONCLUSIONS: Sports that combine jumping in close proximity to other
      players and swift changes of direction while running are most often associated
      with ankle injuries. Future research on ankle injuries is needed to drive the
      development and implementation of more effective preventive interventions.

PMID- 18059995
TI  - Ankle sprain injuries: a 2-year prospective cohort study in female Greek
      professional basketball players.
AB  - CONTEXT: Ankle sprains are a common basketball injury. Therefore, examination of
      risk factors for injury in female professional basketball players is worthwhile.
      OBJECTIVE: To examine rates of ankle sprains, associated time missed from
      participation, and risk factors for injury during 2 consecutive seasons. DESIGN:
      Prospective cohort study. SETTING: Eighteen professional basketball facilities.
      PATIENTS OR OTHER PARTICIPANTS: We observed 204 players from 18 female
      professional basketball teams for 2 consecutive seasons during a 2-year period.
      MAIN OUTCOME MEASURE(S): Using questionnaires, we recorded the incidence of ankle
      sprains, participation time missed, and mechanisms of injury in games and
      practice sessions. Potential risk factors, such as age, body mass, height,
      training experience, and history of ankle sprain, were examined using
      multivariate logistic regression. RESULTS: Fifty of the 204 participants
      sustained ankle injuries; injuries included 32 ankle sprains, which translated to
      an ankle sprain rate of 1.12 per 1000 hours of exposure to injury. The 32 players
      missed 224.4 training and game sessions and an average of 7.01 sessions per
      injury. Most injuries occurred in the key area of the basketball court and were
      the result of contact. Injury rates during games were higher than injury rates
      during practice sessions. Centers, followed by guards and forwards, had the
      highest rate of injury. Players who did not wear an external ankle support had an
      odds ratio of 2.481 for sustaining an ankle sprain. CONCLUSIONS: Female
      professional basketball athletes who did not wear an external ankle support, who
      played in the key area, or who functioned as centers had a higher risk for ankle
      sprain than did other players.

PMID- 18059996
TI  - Time-loss and non-time-loss injuries in youth football players.
AB  - CONTEXT: Estimates suggest that more than 5.5 million youths play football
      annually, and 28% of youth football players (age range = 5 to 14 years) are
      injured each year, resulting in more than 187 000 emergency room visits.
      OBJECTIVE: To analyze time-loss (TL) and non-time-loss (NTL) injury patterns
      across age groups in youth football players. DESIGN: Two-year observational
      cohort. SETTING: Two midwestern communities, including players from the fourth
      through eighth grades and between the ages of 9 and 14 years. PATIENTS OR OTHER
      PARTICIPANTS: A total of 779 players participated, including 296 in grades 4 and
      5; 203 in grade 6; 188 in grade 7; and 92 in grade 8. (Players in the fourth and
      fifth grades participated on the same teams, so we considered them as a single
      group.) MAIN OUTCOME MEASURE(S): Injury frequencies and exposures were collected
      by certified athletic trainers present at each practice and game and used to
      calculate injury rates with 95% confidence intervals (CIs) for both TL and NTL
      injuries across age groups. RESULTS: A total of 474 injuries and 26 565 exposures
      were identified. Injuries were reported by 36.5% of the players, with 14.4%
      reporting more than 1 injury in a season. The overall injury rate per 1000
      athlete-exposures (A-Es) was 17.8 (95% CI = 16.3, 19.5). The injury rate
      increased with each succeeding grade from 14.3 per 1000 A-Es (95% CI = 12.1,
      16.9) in grades 4 and 5 to 21.7 per 1000 A-Es (95% CI = 17.2, 27.3) in grade 8. A
      total of 58.6% of all injuries were NTL. Non-time-loss injuries accounted for
      70.1% of the injuries reported by fourth and fifth graders, 55.1% by sixth
      graders, 64.0% by seventh graders, and 33.8% by eighth graders. The cumulative
      NTL injury rate was 10.5 per 1000 A-Es (95% CI = 9.3, 11.8), and the TL injury
      rate was 7.4 per 1000 A-Es (95% CI = 6.4, 8.5). CONCLUSIONS: Youth football
      players sustained more NTL injuries than TL injuries. We recommend that a first
      aid-certified coach or league official be present at all games and practices.

PMID- 18059997
TI  - Bone mineral density in collegiate female athletes: comparisons among sports.
AB  - CONTEXT: Some female athletes may have decreased bone mineral density (BMD),
      which puts them at higher risk for stress fractures and future osteoporosis.
      OBJECTIVE: To compare site-specific BMD among National Collegiate Athletic
      Association Division I varsity female athletes and to determine predictor
      variables of BMD measurements. DESIGN: Between-groups design. SETTING: University
      health care system. PATIENTS OR OTHER PARTICIPANTS: All women varsity athletes
      were invited to participate in a cross-sectional study. Of 12 sports, we obtained
      complete data from 99 women (mean age = 20.2 +/- 1.3 years) representing
      gymnastics, softball, cross-country, track, field hockey, soccer, crew, and
      swimming/diving. MAIN OUTCOME MEASURE(S): Each participant was weighed, measured,
      and questioned about her menstrual status. Using dual-energy x-ray
      absorptiometry, we measured total-body BMD and region-of-interest scores for
      lumbar spine, pelvis, and average leg (average from right and left leg
      measurements) BMD. Using analyses of covariance, we compared BMD measurements
      among sports at each site while controlling for menstrual status and mass, and we
      performed a stepwise regression analysis to determine significant predictors of
      BMD at each site. RESULTS: Twenty-three athletes were oligomenorrheic or
      amenorrheic. Runners had the lowest total-body (1.079 +/- 0.055 g.cm (-2)) and
      site-specific ( P < .01) BMD values for every site except average leg score when
      compared with gymnasts and softball players. Swimmers and divers had
      significantly lower average leg BMD (1.117 +/- 0.086 g.cm (-2)) than athletes in
      every other sport except runners and rowers ( P < .01). Regression analysis
      revealed only mass and sport as significant predictors of total-body BMD.
      CONCLUSIONS: Runners and swimmers and divers demonstrated some deficits in site
      specific BMD values when compared with athletes in other sports. When treating a
      female varsity athlete, athletic trainers should consider her mass and sport type
      with regard to her bone health.

PMID- 18059998
TI  - Does eccentric exercise reduce pain and improve strength in physically active
      adults with symptomatic lower extremity tendinosis? A systematic review.
AB  - OBJECTIVE: To critically review evidence for the effectiveness of eccentric
      exercise to treat lower extremity tendinoses. DATA SOURCES: Databases used to
      locate randomized controlled trials (RCTs) included PubMed (1980-2006), CINAHL
      (1982-2006), Web of Science (1995-2006), SPORT Discus (1980-2006), Physiotherapy
      Evidence Database (PEDro), and the Cochrane Collaboration Database. Key words
      included tendon, tendonitis, tendinosis, tendinopathy, exercise, eccentric,
      rehabilitation, and therapy. STUDY SELECTION: The criteria for trial selection
      were (1) the literature was written in English, (2) the research design was an
      RCT, (3) the study participants were adults with a clinical diagnosis of
      tendinosis, (4) the outcome measures included pain or strength, and (5) eccentric
      exercise was used to treat lower extremity tendinosis. DATA EXTRACTION: Specific
      data were abstracted from the RCTs, including eccentric exercise protocol,
      adjunctive treatments, concurrent physical activity, and treatment outcome. DATA
      SYNTHESIS: The calculated post hoc statistical power of the selected studies (n =
      11) was low, and the average methodologic score was 5.3/10 based on PEDro
      criteria. Eccentric exercise was compared with no treatment (n = 1), concentric
      exercise (n = 5), an alternative eccentric exercise protocol (n = 1), stretching
      (n = 2), night splinting (n = 1), and physical agents (n = 1). In most trials,
      tendinosis-related pain was reduced with eccentric exercise over time, but only
      in 3 studies did eccentric exercise decrease pain relative to the control
      treatment. Similarly, the RCTs demonstrated that strength-related measures
      improved over time, but none revealed significant differences relative to the
      control treatment. Based on the best evidence available, it appears that
      eccentric exercise may reduce pain and improve strength in lower extremity
      tendinoses, but whether eccentric exercise is more effective than other forms of
      therapeutic exercise for the resolution of tendinosis symptoms remains
      questionable.

PMID- 18059999
TI  - Management of superficial to partial-thickness wounds.
AB  - REFERENCE/CITATION: Wiechula R. The use of moist wound-healing dressings in the
      management of split-thickness skin graft donor sites: a systematic review. Int J
      Nurs Pract. 2003; 9:S9-S17. CLINICAL QUESTION: Do rates of healing, infection,
      and pain differ depending on whether nonmoist or moist dressings are used to
      manage superficial to partial-thickness wounds? DATA SOURCES: Investigations were
      identified by CINAHL, MEDLINE, Pre-MEDLINE, Cochrane Library, Current Contents,
      Health STAR, EMBASE, Expanded Academic Index, and Dissertation Abstracts
      International searches. The search terms included skin, graft, and donor.
      Additional searches were performed with reference lists and bibliographies of
      retrieved studies. STUDY SELECTION: To be included in the review, each study had
      to fulfill the following criteria: it had to be an intraindividual or prospective
      randomized controlled trial of human subjects; it had to include patients with
      postharvest split-thickness skin graft donor sites; it had to evaluate the
      effectiveness of primary and secondary wound dressings; and it had to have
      outcome measures that included healing (objective), infection (subjective), and
      pain (objective). DATA EXTRACTION: Data extraction and study quality assessment
      procedures were developed specifically for this review based on Cochrane
      Collaboration, Centre for Reviews and Dissemination, and Joanna Briggs Institute
      protocols and were performed independently by the author. Details of the
      procedures were not fully explained. The principal outcome measures were healing
      (proportion of sites healed within the study period or time to complete healing),
      rate of infection, and pain scores. The studies were grouped according to broad
      dressing type (nonmoist and moist) and specific types of moist dressings
      (hydrocolloids and polyurethane semipermeable transparent films). When
      comparable, study results were pooled and analyzed with a fixed-effects model.
      Data within broader dressing categories (nonmoist and moist) were analyzed with a
      random-effects model. chi (2) analysis was used to determine heterogeneity among
      the studies. RevMan software (version 4.04; Cochrane Centre, Oxford, UK) was used
      for statistical analysis. MAIN RESULTS: The searches identified 111 studies and 1
      integrative review, of which 58 studies met the inclusion and exclusion criteria.
      Inconsistency and variation in outcome measures and incomplete reporting of
      results prevented analysis of many studies. Wound healing was measured by days to
      complete healing (when dressings could be removed without trauma and pain) and
      wounds healed by day X (removal of dressings at regular intervals). Wound
      infection was subjectively measured based on clinical signs of infection (edema,
      heat, pain, or smell). Visual analog scales were used to measure pain levels.
      Among the broad categories of nonmoist (sterile gauze, fine mesh gauze, Xerofoam
      [Tyco Healthcare Group LP, Mansfield, MA]) and moist (DuoDERM hydrocolloid
      [ConvaTec, Princeton, NJ], Tegaderm transparent film [3M Health Care, St Paul,
      MN], Opsite transparent film [Smith & Nephew, London, UK]) dressings, the
      outcomes of healing, infection, and pain were analyzed. In 6 studies, the
      findings significantly favored moist dressings, compared with nonmoist dressings,
      for days to complete healing (weighted mean difference [WMD] = -3.97, 95%
      confidence interval [CI] = -5.91, -2.02). In 9 studies, wounds healed by day X
      (day 7, 8, 9, 10, or 12) were analyzed. The results were varied and inconclusive
      because of a small number of trials and subjects. Among 10 studies, no
      significant difference was noted in infection rates between nonmoist and moist
      dressings (odds ratio [OR] = 0.41, 95% CI = 0.14, 1.18). Three studies using
      visual analog scales for the outcome of pain were converted into a uniform scale
      of 1 to 10 (10 representing most painful). The findings significantly favored
      moist dressings over nonmoist dressings (WMD = -1.75, 95% CI = -2.94, -0.56).
      Among nonmoist and specific types of moist dressings, a subset analysis was
      performed to examine the outcomes of healing, infection, and pain. For days to
      complete healing, 2 investigations significantly favored hydrocolloid dressings
      over nonmoist dressings (WMD = -2.19, 95% CI = -2.89, -1.49). Additionally, in 2
      studies, hydrocolloid dressings were significantly favored over other moist
      dressings (semiocclusive hydrocolloid and transparent film) for days to complete
      healing (WMD = -1.45, 95% CI = -2.17, -0.74). In 3 studies, the data
      significantly favored polyurethane semipermeable transparent film dressings over
      nonmoist dressings for days to complete healing (WMD = -2.82, 95% CI = -3.58, 
      2.07). For infection rates, 4 studies significantly favored hydrocolloid
      dressings over nonmoist dressings (OR = 0.21, 95% CI = 0.07, 0.65). In 4 other
      studies, polyurethane semipermeable transparent film dressings were significantly
      favored over nonmoist dressings with regard to infection rates (OR = 0.28, 95% CI
      = 0.09, 0.91). For the outcome of pain, varied outcome measures and insufficient
      data prevented analysis among specific types of moist dressings. CONCLUSIONS:
      Moist dressings decreased the days to complete healing and pain scores when
      compared with nonmoist dressings. Among the broad categories of nonmoist and
      moist dressings, no differences were found in infection rates. The data on
      specific types of moist dressings revealed that days to complete healing were
      decreased with hydrocolloid dressings compared with nonmoist and other moist
      dressings. Hydrocolloid dressings also decreased infection rates compared with
      nonmoist dressings. Polyurethane semipermeable transparent film dressings also
      decreased days to complete healing and infection rates compared with nonmoist
      dressings. Overall, the data indicated that hydrocolloid dressings are more
      effective than nonmoist dressings in terms of rates of healing, infection, and
      pain in the management of superficial to partial-thickness wounds. The variations
      in outcome measures among the included studies should be considered in
      interpreting these findings.

PMID- 18060003
TI  - Turning 50--look at what we have become!

PMID- 18060000
TI  - Blisters on the anterior shin in 3 research subjects after a 1-MHz, 1.5-W/cm ,
      continuous ultrasound treatment: a case series.
AB  - CONTEXT: Clinicians should consider multiple factors when estimating tissue
      heating rates. OBJECTIVE: To report 3 separate occurrences of blisters during an
      ultrasound treatment experiment. BACKGROUND: While we were conducting a research
      experiment comparing the measurement capabilities of 2 different intramuscular
      temperature devices, 3 female participants (age = 26.33 +/- 3.79 years, height =
      169.34 +/- 3.89 cm, mass = 63.39 +/- 3.81 kg) out of 16 healthy volunteers (7
      men: age = 22.83 +/- 1.17 years, height = 170.61 +/- 7.77 cm, mass = 74.62 +/-
      19.24 kg; 9 women: age = 24.22 +/- 2.73 years, height = 171.88 +/- 6.35 cm, mass
      = 73.99 +/- 18.55 kg) developed blisters on the anterior shin after a 1-MHz, 1.5
      W/cm (2) continuous ultrasound treatment delivered to the triceps surae muscle.
      DIFFERENTIAL DIAGNOSIS: Allergies; chemical reaction with cleaning agents;
      sunburn; negative interaction between the temperature measurement instruments and
      the ultrasound field; the ultrasound transducer not being calibrated properly,
      producing a nonuniform field and creating a hot spot or heating differently when
      compared with other ultrasound devices; the smaller anatomy of our female
      subjects; or a confounding interaction among these factors. TREATMENT:
      Participants were given standard minor burn care by a physician. UNIQUENESS: (1)
      The development of blisters on the anterior aspect of the shin as a result of an
      ultrasound treatment to the posterior aspect of the triceps surae muscle and (2)
      muscle tissue heating rates ranging from 0.19 degrees C to 1.1 degrees C/min,
      when ultrasound researchers have suggested tissue heating in the range of 0.3
      degrees C/min with these settings. CONCLUSIONS: These adverse events raise
      important questions regarding treatment application and potential differences in
      heating and quality control among different ultrasound devices from different
      manufacturers.

PMID- 18060004
TI  - In unity there is strength!

PMID- 18060001
TI  - Hypopituitarism after multiple concussions: a retrospective case study in an
      adolescent male.
AB  - OBJECTIVE: To describe the development of hypopituitarism in an adolescent
      athlete after multiple concussions and to raise awareness among sports medicine
      clinicians concerning the growing concern of hypopituitarism in concussion injury
      surveillance and management. BACKGROUND: A 14-year-old, previously healthy male
      athlete suffered 4 head traumas over a 4-month period. The first 3 traumas were
      considered by the athlete to be minor and were not reported to medical personnel.
      The fourth trauma was a medically diagnosed concussion suffered during soccer
      play. Over the next year, the patient noted a decline in strength and
      conditioning and a failure to grow. DIFFERENTIAL DIAGNOSIS: After physical
      examination and a full battery of endocrine tests, the patient, then 16.5 years
      old, was diagnosed with hypopituitarism. Follow-up interviews provided evidence
      that at least 2 of the 3 head injuries suffered before the last concussion could
      also be considered concussions, which may have contributed to the severity of the
      last head injury. TREATMENT: The patient is currently being treated with
      physiologic replacement hormones (growth hormone, cortisol, and thyroxine), with
      resumption of linear growth and strength. He is progressing well. UNIQUENESS: In
      the past few years in the medical literature, increased attention has been drawn
      to the occult occurrence of hypopituitarism after traumatic brain injury in
      adults. Initial reports indicate that children are also at risk. To our
      knowledge, this is the first reported case of hypopituitarism after mild
      traumatic brain injury in the sports medicine literature. CONCLUSIONS: Symptoms
      of hypopituitarism are often masked by trauma and postconcussion symptoms and may
      not appear until months or years after the trauma incident, which can lead to
      significant delay in proper diagnosis and treatment. We urge greater vigilance
      by, and training of, sports medicine clinicians toward the goal of recognizing
      the possibility of pituitary disorders after sports concussion.

PMID- 18060005
TI  - Inventory time.

PMID- 18060007
TI  - Diagnosis and management of "an apparent mechanical" femoral mononeuropathy: a
      case study.
AB  - This report describes an apparent case of femoral nerve mononeuropathy in a 58
      year-old equestrian due to mechanical stress. A woman presented at a chiropractic
      office complaining of right buttock pain radiating to the right groin and knee. A
      treatment plan, consisting of chiropractic adjustments in addition to stretching
      and myofascial therapy, was initiated. The goal was to reduce pain and
      inflammation in the sacroiliac articulation by restoring normal biomechanical
      function. A rehabilitation program to alleviate tension in the musculature was
      initiated to reduce mechanical stresses exerted on the femoral nerve. The patient
      received five treatments over a period of three weeks and became asymptomatic.
      Even though peripheral nerve entrapment is an uncommon condition, clinicians must
      not overlook the possibility of a femoral mononeuropathy as it can produce a
      complex presentation and lead to ineffective patient management.

PMID- 18060008
TI  - Allan M. Freedman, LLB: a lawyer's gift to Canadian chiropractors.
AB  - This paper reviews the leadership role, contributions, accolades, and impact of
      Professor Allan Freedman through a 30 year history of service to CMCC and the
      chiropractic profession in Canada. Professor Freedman has served as an educator,
      philanthropist and also as legal counsel. His influence on chiropractic
      organizations and chiropractors during this significant period in the profession
      is discussed.

PMID- 18060009
TI  - Menorrhagia: a synopsis of management focusing on herbal and nutritional
      supplements, and chiropractic.
AB  - INTRODUCTION: To make chiropractors more aware of menorrhagia and how they can
      serve a role in their patient's care and education since women make up 60% of the
      population seeking chiropractic care. METHOD: A review of the biomedical
      literature on menorrhagia was conducted. Items that were retrieved were
      synthesized and interpreted in order to give the best information to practicing
      chiropractors. DISCUSSION: Most of the information available relative to
      menorrhagia is medically oriented. Other treatment options can include:
      chiropractic, various types of herbs, and nutritional supplements. CONCLUSION:
      Knowledge of medical treatment, nutritional supplements, along with chiropractic
      treatment options may be beneficial to doctors in their practice.

PMID- 18060010
TI  - From multidisciplinary to Interdisciplinary--it's all about patient outcomes.

PMID- 18060011
TI  - Ankylosing spondylitis: recent breakthroughs in diagnosis and treatment.
AB  - Ankylosing spondylitis (AS) is generally easy to diagnose when the characteristic
      findings of the "bamboo" spine and fused sacroiliac joints are present on
      radiographs. Unfortunately, these changes are usually seen late in the disease
      after tremendous suffering has been incurred by the patient. Diagnostic delay
      averages seven to ten years. Historically, once the diagnosis was made, the
      treatment options were often inadequate or poorly tolerated in many individuals.
      This condition most often starts in early adulthood when people are typically in
      the earlier stages of their careers, resulting in diminished workforce
      participation and decreased quality of life. If an individual has a family
      physician, this might be the first encounter with a healthcare provider. Quite
      often, the initial practitioner is sought at a public walk-in clinic or
      chiropractic office. In recent years, there have been two major developments in
      the management of AS that make earlier diagnosis possible and offer the hope of
      alleviating pain and preventing structural changes that result in loss of
      function. These developments include the use of magnetic resonance imaging (MRI)
      to visualize the inflammatory changes in the sacroiliac joint and the axial
      spine, and the demonstration that tumor necrosis factor (TNF) blocking agents are
      highly efficacious in reducing spinal inflammation and possibly in slowing
      radiographic progression. This review outlines diagnostic strategies that can
      help identify AS in its earlier stages. Special attention is focused on treatment
      advances, including the use of anti-TNF agents, and how these medications have
      been incorporated into clinical recommendations for daily use.

PMID- 18060013
TI  - Gene systems network inferred from expression profiles in hepatocellular
      carcinogenesis by graphical Gaussian model.
AB  - Hepatocellular carcinoma (HCC) in a liver with advanced-stage chronic hepatitis C
      (CHC) is induced by hepatitis C virus, which chronically infects about 170
      million people worldwide. To elucidate the associations between gene groups in
      hepatocellular carcinogenesis, we analyzed the profiles of the genes
      characteristically expressed in the CHC and HCC cell stages by a statistical
      method for inferring the network between gene systems based on the graphical
      Gaussian model. A systematic evaluation of the inferred network in terms of the
      biological knowledge revealed that the inferred network was strongly involved in
      the known gene-gene interactions with high significance (P < 10(-4)), and that
      the clusters characterized by different cancer-related responses were associated
      with those of the gene groups related to metabolic pathways and morphological
      events. Although some relationships in the network remain to be interpreted, the
      analyses revealed a snapshot of the orchestrated expression of cancer-related
      groups and some pathways related with metabolisms and morphological events in
      hepatocellular carcinogenesis, and thus provide possible clues on the disease
      mechanism and insights that address the gap between molecular and clinical
      assessments.

PMID- 18060012
TI  - Stress and memory: behavioral effects and neurobiological mechanisms.
AB  - Stress is a potent modulator of learning and memory processes. Although there
      have been a few attempts in the literature to explain the diversity of effects
      (including facilitating, impairing, and lack of effects) described for the impact
      of stress on memory function according to single classification criterion, they
      have proved insufficient to explain the whole complexity of effects. Here, we
      review the literature in the field of stress and memory interactions according to
      five selected classifying factors (source of stress, stressor duration, stressor
      intensity, stressor timing with regard to memory phase, and learning type) in an
      attempt to develop an integrative model to understand how stress affects memory
      function. Summarizing on those conditions in which there was enough information,
      we conclude that high stress levels, whether intrinsic (triggered by the
      cognitive challenge) or extrinsic (induced by conditions completely unrelated to
      the cognitive task), tend to facilitate Pavlovian conditioning (in a linear
      asymptotic manner), while being deleterious for spatial/explicit information
      processing (which with regard to intrinsic stress levels follows an inverted U
      shape effect). Moreover, after reviewing the literature, we conclude that all
      selected factors are essential to develop an integrative model that defines the
      outcome of stress effects in memory processes. In parallel, we provide a brief
      review of the main neurobiological mechanisms proposed to account for the
      different effects of stress in memory function. Glucocorticoids were found as a
      common mediating mechanism for both the facilitating and impairing actions of
      stress in different memory processes and phases. Among the brain regions
      implicated, the hippocampus, amygdala, and prefrontal cortex were highlighted as
      critical for the mediation of stress effects.

PMID- 18060015
TI  - Protection against malaria a real possibility.

PMID- 18060014
TI  - RAR/RXR and PPAR/RXR Signaling in Spinal Cord Injury.
AB  - The retinoid acid receptors (RAR) and peroxisome proliferator-activated receptors
      (PPAR) have been implicated in the regulation of inflammatory reactions. Both
      receptor families contain ligand-activated transcription factors which form
      heterodimers with retinoid X receptors (RXR). We review data that imply RAR/RXR
      and PPAR/RXR pathways in physiological reactions after spinal cord injury.
      Experiments show how RAR signaling may improve axonal regeneration and modulate
      reactions of glia cells. While anti-inflammatory properties of PPAR are well
      documented in the periphery, their possible roles in the central nervous system
      have only recently become evident. Due to its anti-inflammatory function this
      transcription factor family promises to be a useful target after spinal cord or
      brain lesions.

PMID- 18060016
TI  - How to write a scientific masterpiece.
AB  - I've been asked several times to give talks about various aspects of the
      scientific publishing enterprise, and sometimes to comment specifically on how to
      write a manuscript that will have maximal impact. While many in my audiences have
      felt that my presentations are designed for students and trainees, I hope
      everyone listens, as sometimes even established scientists are prone to making
      mistakes. I hope here to outline a few pointers that will help your manuscripts
      skate through the submission and peer review process. Some points may be
      elementary, but all bear repeating.

PMID- 18060017
TI  - Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain
      disorders.
AB  - The voltage-gated sodium-channel type IX alpha subunit, known as Na(v)1.7 and
      encoded by the gene SCN9A, is located in peripheral neurons and plays an
      important role in action potential production in these cells. Recent genetic
      studies have identified Na(v)1.7 dysfunction in three different human pain
      disorders. Gain-of-function missense mutations in Na(v)1.7 have been shown to
      cause primary erythermalgia and paroxysmal extreme pain disorder, while nonsense
      mutations in Na(v)1.7 result in loss of Na(v)1.7 function and a condition known
      as channelopathy-associated insensitivity to pain, a rare disorder in which
      affected individuals are unable to feel physical pain. This review highlights
      these recent developments and discusses the critical role of Na(v)1.7 in pain
      sensation in humans.

PMID- 18060018
TI  - On future's doorstep: RNA interference and the pharmacopeia of tomorrow.
AB  - Small molecules and antibodies have revolutionized the treatment of malignant
      diseases and appear promising for the treatment of many others. Nonetheless,
      there are many candidate therapeutic targets that are not amenable to attack by
      the current generation of targeted therapies, and in a small but growing number
      of patients, resistance to initially successful treatments evolves. This Review
      Series on the medicinal promise of posttranscriptional gene silencing with small
      interfering RNA and other molecules capable of inducing RNA interference (RNAi)
      is motivated by the hypothesis that effectors of RNAi can be developed into
      effective drugs for treating malignancies as well as many other types of disease.
      As this Review Series points out, there is still much to do, but many in the
      field now hope that the time has finally arrived when "antisense" therapies will
      finally come of age and fulfill their promise as the magic bullets of the 21st
      century.

PMID- 18060019
TI  - Chemical modification: the key to clinical application of RNA interference?
AB  - RNA interference provides a potent and specific method for controlling gene
      expression in human cells. To translate this potential into a broad new family of
      therapeutics, it is necessary to optimize the efficacy of the RNA-based drugs. As
      discussed in this Review, it might be possible to achieve this optimization using
      chemical modifications that improve their in vivo stability, cellular delivery,
      biodistribution, pharmacokinetics, potency, and specificity.

PMID- 18060020
TI  - Nonviral delivery of synthetic siRNAs in vivo.
AB  - Sequence-specific gene silencing using small interfering RNA (siRNA) is a Nobel
      prize-winning technology that is now being evaluated in clinical trials as a
      potentially novel therapeutic strategy. This article provides an overview of the
      major pharmaceutical challenges facing siRNA therapeutics, focusing on the
      delivery strategies for synthetic siRNA duplexes in vivo, as this remains one of
      the most important issues to be resolved. This article also highlights the
      importance of understanding the genocompatibility/toxicogenomics of siRNA
      delivery reagents in terms of their impact on gene-silencing activity and
      specificity. Collectively, this information is essential for the selection of
      optimally acting siRNA delivery system combinations for the many proposed
      applications of RNA interference.

PMID- 18060021
TI  - Therapeutic application of RNAi: is mRNA targeting finally ready for prime time?
AB  - With unprecedented speed, RNA interference (RNAi) has advanced from its basic
      discovery in lower organisms to becoming a powerful genetic tool and perhaps our
      single most promising biotherapeutic for a wide array of diseases. Numerous
      studies document RNAi efficacy in laboratory animals, and the first clinical
      trials are underway and thus far suggest that RNAi is safe to use in humans. Yet
      substantial hurdles have also surfaced and must be surmounted before therapeutic
      RNAi applications can become a standard therapy. Here we review the most critical
      roadblocks and concerns for clinical RNAi transition, delivery, and safety. We
      highlight emerging solutions and concurrently discuss novel therapeutic RNAi
      based concepts. The current rapid advances create realistic optimism that the
      establishment of RNAi as a new and potent clinical modality in humans is near.

PMID- 18060022
TI  - B cell depletion: a novel therapy for autoimmune diabetes?
AB  - Autoimmune diabetes is believed to be mediated primarily by T cells. However, B
      cells have been implicated in the pathogenesis of the disease in NOD mice.
      Although preclinical studies have been limited by the absence of anti-CD20
      reagents that can induce B cell depletion in mice, a clinical trial using the B
      cell-depleting anti-CD20 monoclonal antibody rituximab (Rituxan) is underway in
      type 1 diabetes patients. In this issue of the JCI, Hu et al. describe the
      generation of transgenic NOD mice that express human CD20 on B cells (see the
      related article beginning on page 3857). They show that anti-CD20 therapy induces
      B cell depletion in these mice and offers some level of protection against
      diabetes. Although many questions remain unanswered, this mouse model represents
      the first opportunity to evaluate the potential value of rituximab as a novel
      therapy for autoimmune diabetes.

PMID- 18060023
TI  - Every allograft needs a silver lining.
AB  - The development of chronic allograft rejection is based on the hypothesis that
      cumulative, time-dependent tissue injury eventually leads to a fibrotic response.
      In this issue of the JCI, Babu and colleagues found that alloimmune-mediated
      microvascular loss precedes tissue damage in murine orthotopic tracheal
      allografts (see the related article beginning on page 3774). The concept that
      injury to the endothelium may precede airway fibrosis suggests that interventions
      to maintain vascular integrity may be important, especially in the case of lung
      transplantation. Further, for all solid organ allografts, it is possible that the
      key to long-term allograft survival is physiological vascular repair at early
      times following transplantation.

PMID- 18060024
TI  - Staying awake puts pressure on brain arousal systems.
AB  - Many brain centers are involved in keeping us awake. One example is the recently
      discovered hypocretin system located in the posterior hypothalamus. In this issue
      of the JCI, Rao et al. show that, in mice, synapses targeting hypocretin neurons
      become stronger when wakefulness is prolonged beyond its physiological duration
      (see the related article beginning on page 4022). This increase in synaptic
      strength may be one of the mechanisms that help us to stay awake when we are
      sleep deprived, but it may also represent one of the signals telling the brain
      that it is time to sleep.

PMID- 18060025
TI  - Structural reengineering of imatinib to decrease cardiac risk in cancer therapy.
AB  - Imatinib, a selective, small-molecule tyrosine kinase inhibitor, has life-saving
      clinical activity in certain cancers, but questions have been raised about the
      potential for cardiac toxicity through inhibition of its target, ABL kinase. In
      this issue of the JCI, Fernandez et al. describe a novel method by which the ABL
      inhibitory activity of imatinib was deleted by modifying its chemical structure
      (see the related article beginning on page 4044). The anticancer activity of the
      reengineered agent, called WBZ_4, was instead preserved against gastrointestinal
      stromal tumors in both in vitro and in vivo models via inhibition of KIT tyrosine
      kinase, and the desired safety was demonstrated with less cardiotoxicity of WBZ_4
      compared with imatinib via the inhibition of JNK. The study shows that structural
      reengineering of a kinase-inhibitory drug to improve tolerability while
      preserving efficacy is feasible.

PMID- 18060026
TI  - The weight of cell identity.
AB  - Recent studies involving molecular modification of adult somatic cells have
      pointed to a remarkable plasticity in cell identity. In this issue of the JCI,
      Koh and colleagues assessed whether bone marrow-derived cells could alter their
      fate under circumstances conducive to adipocyte generation in vivo (see the
      related article beginning on page 3684). These cells remained true to their
      roots, indicating how difficult it will be to exploit cell plasticity for
      therapeutic purposes.

PMID- 18060027
TI  - Targeting mutant p53 shows promise for sunscreens and skin cancer.
AB  - Chronic exposure to UV light is a risk factor for skin cancer in which signature
      mutations in the p53 tumor suppressor gene occur due to DNA damage and contribute
      to cancer development. In this issue of the JCI, Tang et al. report on their
      study of a nonimmunodeficient mouse model of UVB-induced skin cancer and human
      skin carcinoma cells and show that the mutant p53 conformation-modifying drug CP
      31398 not only treats these tumors but also prevents them (see the related
      article beginning on page 3753). These studies have important implications for
      chemoprevention as well as therapy of common, mutant p53-driven tumors.

PMID- 18060028
TI  - IL-6 involvement in epithelial cancers.
AB  - In this issue of the JCI, two reports provide intriguing new information on the
      role of the inflammatory cytokine IL-6 in breast and lung cancer. The study by
      Sansone et al. implicates IL-6 in the instigation of malignant properties in
      breast cancer stem cells (see the related article beginning on page 3988). The
      study by Gao et al. identifies mutant variants of EGFR as inducers of IL-6 in
      lung adenocarcinomas (see the related article beginning on page 3846). These
      studies add to our understanding of potential roles for IL-6 in cancer and
      further motivate investigations of IL-6-targeted chemotherapeutics.

PMID- 18060029
TI  - Bone marrow-derived circulating progenitor cells fail to transdifferentiate into
      adipocytes in adult adipose tissues in mice.
AB  - Little is known about whether bone marrow-derived circulating progenitor cells
      (BMDCPCs) can transdifferentiate into adipocytes in adipose tissues or play a
      role in expanding adipocyte number during adipose tissue growth. Using a mouse
      bone marrow transplantation model, we addressed whether BMDCPCs can
      transdifferentiate into adipocytes under standard conditions as well as in the
      settings of diet-induced obesity, rosiglitazone treatment, and exposure to G-CSF.
      We also addressed the possibility of transdifferentiation to adipocytes in a
      murine parabiosis model. In each of these settings, our findings indicated that
      BMDCPCs did not transdifferentiate into either unilocular or multilocular
      adipocytes in adipose tissues. Most BMDCPCs became resident and phagocytic
      macrophages in adipose tissues--which resembled transdifferentiated multilocular
      adipocytes by appearance, but displayed cell surface markers characteristic for
      macrophages - in the absence of adipocyte marker expression. When exposed to
      adipogenic medium in vitro, bone marrow cells differentiated into multilocular,
      but not unilocular, adipocytes, but transdifferentiation was not observed in
      vivo, even in the contexts of adipose tissue regrowth or dermal wound healing.
      Our results suggest that BMDCPCs do not transdifferentiate into adipocytes in
      vivo and play little, if any, role in expanding the number of adipocytes during
      the growth of adipose tissues.

PMID- 18060030
TI  - CP-31398 restores mutant p53 tumor suppressor function and inhibits UVB-induced
      skin carcinogenesis in mice.
AB  - Mutations in the tumor suppressor p53 are detectable in over 50% of all human
      malignancies. Mutant p53 protein is incapable of transactivating its downstream
      target genes that are required for DNA repair and apoptosis. Chronic exposure to
      UVB induces p53 mutations and is carcinogenic in both murine and human skin. CP
      31398, a styrylquinazoline compound, restores the tumor suppressor functions of
      mutant forms of p53 in tumor cells. However, its effectiveness in vivo remains
      unclear. Here, we demonstrate that CP-31398 blocked UVB-induced skin
      carcinogenesis and was associated with increases in p53, p21, and BclXs. CP-31398
      downregulated Bcl2, proliferating nuclear cell antigen, and cyclin D1. Activation
      of caspase-3 and cleavage of poly (ADP-ribose) polymerase also occurred in both
      tumor and perilesional skin following treatment. CP-31398 induced the expression
      of p53-dependent target proteins, and this was followed by apoptosis in UVB
      irradiated wild-type mice but not in their p53-deficient littermates. Similar
      effects were observed in human skin carcinoma A431 cells expressing mutant p53.
      In addition, CP-31398 induced mitochondrial translocation of p53, leading to
      changes in mitochondrial membrane permeability pore transition (MPT) and
      consequent cytochrome c release in these cells. Blocking MPT diminished p53
      translocation and apoptosis. These studies indicate that reconstituting p53 tumor
      suppressor functions in vivo by small molecular weight compounds may block the
      pathogenesis and progression of skin cancer.

PMID- 18060031
TI  - Microvascular destruction identifies murine allografts that cannot be rescued
      from airway fibrosis.
AB  - Small airway fibrosis (bronchiolitis obliterans syndrome) is the primary obstacle
      to long-term survival following lung transplantation. Here, we show the
      importance of functional microvasculature in the prevention of epithelial loss
      and fibrosis due to rejection and for the first time, relate allograft
      microvascular injury and loss of tissue perfusion to immunotherapy-resistant
      rejection. To explore the role of alloimmune rejection and airway ischemia in the
      development of fibroproliferation, we used a murine orthotopic tracheal
      transplant model. We determined that transplants were reperfused by connection of
      recipient vessels to donor vessels at the surgical anastomosis site.
      Microcirculation through the newly formed vascular anastomoses appeared partially
      dependent on VEGFR2 and CXCR2 pathways. In the absence of immunosuppression, the
      microvasculature in rejecting allografts exhibited vascular complement
      deposition, diminished endothelial CD31 expression, and absent perfusion prior to
      the onset of fibroproliferation. Rejecting grafts with extensive endothelial cell
      injury were refractory to immunotherapy. After early microvascular loss,
      neovascularization was eventually observed in the membranous trachea, indicating
      a reestablishment of graft perfusion in established fibrosis. One implication of
      this study is that bronchial artery revascularization at the time of lung
      transplantation may decrease the risk of subsequent airway fibrosis.

PMID- 18060032
TI  - Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production
      in human lung adenocarcinomas.
AB  - Persistently activated or tyrosine-phosphorylated STAT3 (pSTAT3) is found in 50%
      of lung adenocarcinomas. pSTAT3 is found in primary adenocarcinomas and cell
      lines harboring somatic-activating mutations in the tyrosine kinase domain of
      EGFR. Treatment of cell lines with either an EGFR inhibitor or an src kinase
      inhibitor had no effect on pSTAT3 levels, whereas a pan-JAK inhibitor (P6)
      blocked activation of STAT3 and inhibited tumorigenesis. Cell lines expressing
      these persistently activated mutant EGFRs also produced high IL-6 levels, and
      blockade of the IL-6/gp130/JAK pathway led to a decrease in pSTAT3 levels. In
      addition, reduction of IL-6 levels by RNA interference led to a decrease in
      tumorigenesis. Introduction of persistently activated EGFR into immortalized
      breast epithelial cells led to tumorigenesis, IL-6 expression, and STAT3
      activation, all of which could be inhibited with P6 or gp130 blockade.
      Furthermore, inhibition of EGFR activity in multiple cell lines partially blocked
      transcription of IL-6 and concurrently decreased production and release of IL-6.
      Finally, immunohistochemical analysis revealed a positive correlation between
      pSTAT3 and IL-6 positivity in primary lung adenocarcinomas. Therefore, mutant
      EGFR could activate the gp130/JAK/STAT3 pathway by means of IL-6 upregulation in
      primary human lung adenocarcinomas, making this pathway a potential target for
      cancer treatment.

PMID- 18060033
TI  - Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes
      in mice.
AB  - The precise roles of B cells in promoting the pathogenesis of type 1 diabetes
      remain undefined. Here, we demonstrate that B cell depletion in mice can prevent
      or delay diabetes, reverse diabetes after frank hyperglycemia, and lead to the
      development of cells that suppress disease. To determine the efficacy and
      potential mechanism of therapeutic B cell depletion, we generated a transgenic
      NOD mouse expressing human CD20 (hCD20) on B cells. A single cycle of treatment
      with an antibody specific for hCD20 temporarily depleted B cells and
      significantly delayed and/or reduced the onset of diabetes. Furthermore, disease
      established to the point of clinical hyperglycemia could be reversed in over one
      third of diabetic mice. Why B cell depletion is therapeutic for a variety of
      autoimmune diseases is unclear, although effects on antibodies, cytokines, and
      antigen presentation to T cells are thought to be important. In B cell-depleted
      NOD mice, we identified what we believe is a novel mechanism by which B cell
      depletion may lead to long-term remission through expansion of Tregs and
      regulatory B cells. Our results demonstrate clinical efficacy even in established
      disease and identify mechanisms for therapeutic action that will guide design and
      evaluation of parallel studies in patients.

PMID- 18060034
TI  - In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven
      atopic inflammation.
AB  - Thymic stromal lymphopoietin (TSLP) potently induces deregulation of Th2
      responses, a hallmark feature of allergic inflammatory diseases such as asthma,
      atopic dermatitis, and allergic rhinitis. However, direct downstream in vivo
      mediators in the TSLP-induced atopic immune cascade have not been identified. In
      our current study, we have shown that OX40 ligand (OX40L) is a critical in vivo
      mediator of TSLP-mediated Th2 responses. Treating mice with OX40L-blocking
      antibodies substantially inhibited immune responses induced by TSLP in the lung
      and skin, including Th2 inflammatory cell infiltration, cytokine secretion, and
      IgE production. OX40L-blocking antibodies also inhibited antigen-driven Th2
      inflammation in mouse and nonhuman primate models of asthma. This treatment
      resulted in both blockade of the OX40-OX40L receptor-ligand interaction and
      depletion of OX40L-positive cells. The use of a blocking, OX40L-specific mAb thus
      presents a promising strategy for the treatment of allergic diseases associated
      with pathologic Th2 immune responses.

PMID- 18060035
TI  - STAT1 promotes megakaryopoiesis downstream of GATA-1 in mice.
AB  - Thrombocytosis is associated with inflammation, and certain inflammatory
      cytokines, including IFN-gamma, stimulate megakaryocyte and platelet production.
      However, the roles of IFN-gamma and its downstream effector STAT1 in
      megakaryocyte development are poorly understood. We previously reported that
      STAT1 expression was significantly downregulated in Gata1-knockdown murine
      megakaryocytes, which also have impaired terminal maturation. Here, we show that
      ectopic expression of STAT1, or its target effector IRF-1, rescued multiple
      defects in Gata1-deficient megakaryopoiesis in mice, inducing polyploidization
      and expression of a subset of platelet-expressing genes. Enforced expression of
      STAT1, IRF-1, or GATA-1 enhanced phosphorylation of STAT1, STAT3, and STAT5 in
      cultured Gata1-deficient murine megakaryocytes, with concomitant megakaryocyte
      maturation. In contrast, enhanced thrombopoietin signaling, conferred by enforced
      expression of constitutively active JAK2 or c-MPL, induced phosphorylation of
      STAT3 and STAT5, but not STAT1, and failed to rescue megakaryocyte maturation.
      Finally, megakaryocytes from Stat1(-/-) mice were defective in polyploidization.
      Together, these findings reveal a unique role for STAT1 in megakaryopoiesis and
      provide new insights into how GATA-1 regulates this process. Our studies
      elucidate potential mechanisms by which various inflammatory disorders can cause
      elevated platelet counts.

PMID- 18060036
TI  - IL-6 triggers malignant features in mammospheres from human ductal breast
      carcinoma and normal mammary gland.
AB  - High serum levels of IL-6 correlate with poor outcome in breast cancer patients.
      However, no data are available on the relationship between IL-6 and mammary
      stem/progenitor cells, which may fuel the genesis of breast cancer in vivo.
      Herein, we address this issue in the MCF-7 breast cancer cell line and in primary
      human mammospheres (MS), multicellular structures enriched in stem/progenitor
      cells of the mammary gland. MS from node invasive breast carcinoma tissues
      expressed IL-6 mRNA at higher levels than did MS from matched non-neoplastic
      mammary glands. In addition, IL-6 mRNA was detected only in basal-like breast
      carcinoma tissues, an aggressive breast carcinoma variant showing stem cell
      features. IL-6 treatment triggered Notch-3-dependent upregulation of the Notch
      ligand Jagged-1 and promotion of MS and MCF-7-derived spheroid growth. Moreover,
      IL-6 induced Notch-3-dependent upregulation of the carbonic anhydrase IX gene and
      promoted a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS. Finally,
      autocrine IL-6 signaling relied upon Notch-3 activity to sustain the aggressive
      features of MCF-7-derived hypoxia-selected cells. In conclusion, these data
      support the hypothesis that IL-6 induces malignant features in Notch-3-expressing
      stem/progenitor cells from human ductal breast carcinoma and normal mammary
      gland.

PMID- 18060037
TI  - Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse
      hypocretin/orexin neurons.
AB  - Sleep is a natural process that preserves energy, facilitates development, and
      restores the nervous system in higher animals. Sleep loss resulting from
      physiological and pathological conditions exerts tremendous pressure on neuronal
      circuitry responsible for sleep-wake regulation. It is not yet clear how acute
      and chronic sleep loss modify neuronal activities and lead to adaptive changes in
      animals. Here, we show that acute and chronic prolonged wakefulness in mice
      induced by modafinil treatment produced long-term potentiation (LTP) of
      glutamatergic synapses on hypocretin/orexin neurons in the lateral hypothalamus,
      a well-established arousal/wake-promoting center. A similar potentiation of
      synaptic strength at glutamatergic synapses on hypocretin/orexin neurons was also
      seen when mice were sleep deprived for 4 hours by gentle handling. Blockade of
      dopamine D1 receptors attenuated prolonged wakefulness and synaptic plasticity in
      these neurons, suggesting that modafinil functions through activation of the
      dopamine system. Also, activation of the cAMP pathway was not able to further
      induce LTP at glutamatergic synapses in brain slices from mice treated with
      modafinil. These results indicate that synaptic plasticity due to prolonged
      wakefulness occurs in circuits responsible for arousal and may contribute to
      changes in the brain and body of animals experiencing sleep loss.

PMID- 18060038
TI  - An anticancer C-Kit kinase inhibitor is reengineered to make it more active and
      less cardiotoxic.
AB  - Targeting kinases is central to drug-based cancer therapy but remains challenging
      because the drugs often lack specificity, which may cause toxic side effects.
      Modulating side effects is difficult because kinases are evolutionarily and hence
      structurally related. The lack of specificity of the anticancer drug imatinib
      enables it to be used to treat chronic myeloid leukemia, where its target is the
      Bcr-Abl kinase, as well as a proportion of gastrointestinal stromal tumors
      (GISTs), where its target is the C-Kit kinase. However, imatinib also has
      cardiotoxic effects traceable to its impact on the C-Abl kinase. Motivated by
      this finding, we made a modification to imatinib that hampers Bcr-Abl inhibition;
      refocuses the impact on the C-Kit kinase; and promotes inhibition of an
      additional target, JNK, a change that is required to reinforce prevention of
      cardiotoxicity. We established the molecular blueprint for target discrimination
      in vitro using spectrophotometric and colorimetric assays and through a phage
      displayed kinase screening library. We demonstrated controlled inhibitory impact
      on C-Kit kinase in human cell lines and established the therapeutic impact of the
      engineered compound in a novel GIST mouse model, revealing a marked reduction of
      cardiotoxicity. These findings identify the reengineered imatinib as an agent to
      treat GISTs with curbed side effects and reveal a bottom-up approach to control
      drug specificity.

PMID- 18060040
TI  - Inhibition of apolipoprotein B100 secretion by lipid-induced hepatic endoplasmic
      reticulum stress in rodents.
AB  - ER stress can cause hepatic insulin resistance and steatosis. Increased VLDL
      secretion could protect the liver from ER stress-induced steatosis, but the
      effect of lipid-induced ER stress on the secretion of VLDL is unknown. To
      determine the effect of lipids on hepatic ER stress and VLDL secretion, we
      treated McA-RH7777 liver cells with free fatty acids. Prolonged exposure
      increased cell triglycerides, induced steatosis, and increased ER stress. Effects
      on apoB100 secretion, which is required for VLDL assembly, were parabolic, with
      moderate free fatty acid exposure increasing apoB100 secretion, while greater
      lipid loading inhibited apoB100 secretion. This decreased secretion at higher
      lipid levels was due to increased protein degradation through both proteasomal
      and nonproteasomal pathways and was dependent on the induction of ER stress.
      These findings were supported in vivo, where intravenous infusion of oleic acid
      (OA) in mice increased ER stress in a duration-dependent manner. apoB secretion
      was again parabolic, stimulated by moderate, but not prolonged, OA infusion.
      Inhibition of ER stress was able to restore OA-stimulated apoB secretion after
      prolonged OA infusion. These results suggest that excessive ER stress in response
      to increased hepatic lipids may decrease the ability of the liver to secrete
      triglycerides by limiting apoB secretion, potentially worsening steatosis.

PMID- 18060039
TI  - Neuroinflammation, Oxidative Stress and the Pathogenesis of Parkinson's Disease.
AB  - Neuroinflammatory processes play a significant role in the pathogenesis of
      Parkinson's disease (PD). Epidemiologic, animal, human, and therapeutic studies
      all support the presence of an neuroinflammatory cascade in disease. This is
      highlighted by the neurotoxic potential of microglia . In steady state, microglia
      serve to protect the nervous system by acting as debris scavengers, killers of
      microbial pathogens, and regulators of innate and adaptive immune responses. In
      neurodegenerative diseases, activated microglia affect neuronal injury and death
      through production of glutamate, pro-inflammatory factors, reactive oxygen
      species, quinolinic acid amongst others and by mobilization of adaptive immune
      responses and cell chemotaxis leading to transendothelial migration of
      immunocytes across the blood-brain barrier and perpetuation of neural damage. As
      disease progresses, inflammatory secretions engage neighboring glial cells,
      including astrocytes and endothelial cells, resulting in a vicious cycle of
      autocrine and paracrine amplification of inflammation perpetuating tissue injury.
      Such pathogenic processes contribute to neurodegeneration in PD. Research from
      others and our own laboratories seek to harness such inflammatory processes with
      the singular goal of developing therapeutic interventions that positively affect
      the tempo and progression of human disease.

PMID- 18060041
TI  - Adoptive transfer of effector CD8+ T cells derived from central memory cells
      establishes persistent T cell memory in primates.
AB  - The adoptive transfer of antigen-specific T cells that have been expanded ex vivo
      is being actively pursued to treat infections and malignancy in humans. The T
      cell populations that are available for adoptive immunotherapy include both
      effector memory and central memory cells, and these differ in phenotype,
      function, and homing. The efficacy of adoptive immunotherapy requires that
      transferred T cells persist in vivo, but identifying T cells that can
      reproducibly survive in vivo after they have been numerically expanded by in
      vitro culture has proven difficult. Here we show that in macaques, antigen
      specific CD8(+) T cell clones derived from central memory T cells, but not
      effector memory T cells, persisted long-term in vivo, reacquired phenotypic and
      functional properties of memory T cells, and occupied memory T cell niches. These
      results demonstrate that clonally derived CD8+ T cells isolated from central
      memory T cells are distinct from those derived from effector memory T cells and
      retain an intrinsic capacity that enables them to survive after adoptive transfer
      and revert to the memory cell pool. These results could have significant
      implications for the selection of T cells to expand or to engineer for adoptive
      immunotherapy of human infections or malignancy.

PMID- 18060042
TI  - Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a
      mouse model of arthritis.
AB  - TLRs may contribute to the progression of rheumatoid arthritis through
      recognition of microbial or host-derived ligands found in arthritic joints. Here,
      we show that TLR2 and TLR4, but not TLR9, are involved in the pathogenesis of
      autoimmune arthritis and play distinct roles in the regulation of T cells and
      cytokines. We investigated the involvement of TLR2, TLR4, and TLR9 in the
      progression of arthritis using IL-1 receptor antagonist-knockout (IL1rn-/-) mice,
      which spontaneously develop an autoimmune T cell-mediated arthritis. Spontaneous
      onset of arthritis was dependent on TLR activation by microbial flora, as germ
      free mice did not develop arthritis. Clinical and histopathological evaluation of
      IL1rn-/-Tlr2-/- mice revealed more severe arthritis, characterized by reduced
      suppressive function of Tregs and substantially increased IFN-gamma production by
      T cells. IL1rn-/-Tlr4-/- mice were, in contrast, protected against severe
      arthritis and had markedly lower numbers of Th17 cells and a reduced capacity to
      produce IL-17. A lack of Tlr9 did not affect the progression of arthritis. While
      any therapeutic intervention targeting TLR2 still seems complicated, the strict
      position of TLR4 upstream of a number of pathogenic cytokines including IL-17
      provides an interesting potential therapeutic target for rheumatoid arthritis.

PMID- 18060043
TI  - A shed form of LDL receptor-related protein-1 regulates peripheral nerve injury
      and neuropathic pain in rodents.
AB  - Injury to the peripheral nervous system (PNS) initiates a response controlled by
      multiple extracellular mediators, many of which contribute to the development of
      neuropathic pain. Schwann cells in an injured nerve demonstrate increased
      expression of LDL receptor-related protein-1 (LRP1), an endocytic receptor for
      diverse ligands and a cell survival factor. Here we report that a fragment of
      LRP1, in which a soluble or shed form of LRP1 with an intact alpha-chain (sLRP
      alpha), was shed by Schwann cells in vitro and in the PNS after injury. Injection
      of purified sLRP-alpha into mouse sciatic nerves prior to chronic constriction
      injury (CCI) inhibited p38 MAPK activation (P-p38) and decreased expression of
      TNF-alpha and IL-1beta locally. sLRP-alpha also inhibited CCI-induced spontaneous
      neuropathic pain and decreased inflammatory cytokine expression in the spinal
      dorsal horn, where neuropathic pain processing occurs. In cultures of Schwann
      cells, astrocytes, and microglia, sLRP-alpha inhibited TNF-alpha-induced
      activation of p38 MAPK and ERK/MAPK. The activity of sLRP-alpha did not involve
      TNF-alpha binding, but rather glial cell preconditioning, so that the subsequent
      response to TNF-alpha was inhibited. Our results show that sLRP-alpha is
      biologically active and may attenuate neuropathic pain. In the PNS, the function
      of LRP1 may reflect the integrated activities of the membrane-anchored and shed
      forms of LRP1.

PMID- 18060044
TI  - Parasympathetic response in chick myocytes and mouse heart is controlled by
      SREBP.
AB  - Parasympathetic stimulation of the heart, which provides protection from
      arrhythmias and sudden death, involves activation of the G protein-coupled inward
      rectifying K+ channel GIRK1/4 and results in an acetylcholine-sensitive K+
      current, I KACh. We describe a unique relationship between lipid homeostasis, the
      lipid-sensitive transcription factor SREBP-1, regulation of the cardiac
      parasympathetic response, and the development of ventricular arrhythmia. In
      embryonic chick atrial myocytes, lipid lowering by culture in lipoprotein
      depleted serum increased SREBP-1 levels, GIRK1 expression, and I KACh activation.
      Regulation of the GIRK1 promoter by SREBP-1 and lipid lowering was dependent on
      interaction with 2 tandem sterol response elements and an upstream E-box motif.
      Expression of dominant negative SREBP-1 (DN-SREBP-1) reversed the effect of lipid
      lowering on I KACh and GIRK1. In SREBP-1 knockout mice, both the response of the
      heart to parasympathetic stimulation and the expression of GIRK1 were reduced
      compared with WT. I KACh, attenuated in atrial myocytes from SREBP-1 knockout
      mice, was stimulated by SREBP-1 expression. Following myocardial infarction,
      SREBP-1 knockout mice were twice as likely as WT mice to develop ventricular
      tachycardia in response to programmed ventricular stimulation. These results
      demonstrate a relationship between lipid metabolism and parasympathetic response
      that may play a role in arrhythmogenesis.

PMID- 18060045
TI  - Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor
      growth in mice.
AB  - 4-1BB is a major costimulatory receptor that promotes the survival and expansion
      of activated T cells. Administration of agonistic anti-4-1BB Abs has been
      previously shown to enhance tumor immunity in mice. Abs are cell-based products
      posing significant cost, manufacturing, and regulatory challenges. Aptamers are
      oligonucleotide-based ligands that exhibit specificity and avidity comparable to,
      or exceeding, that of Abs. To date, various aptamers have been shown to inhibit
      the function of their cognate target. Here, we have described the development of
      an aptamer that binds 4-1BB expressed on the surface of activated mouse T cells
      and shown that multivalent configurations of the aptamer costimulated T cell
      activation in vitro and mediated tumor rejection in mice. Because aptamers can be
      chemically synthesized, manufacturing and the regulatory approval process should
      be substantially simpler and less costly than for Abs. Agonistic aptamers could
      therefore represent a superior alternative to Abs for the therapeutic
      manipulation of the immune system.

PMID- 18060046
TI  - Tumor escape in a Wnt1-dependent mouse breast cancer model is enabled by
      p19Arf/p53 pathway lesions but not p16 Ink4a loss.
AB  - Breast cancers frequently progress or relapse during targeted therapy, but the
      molecular mechanisms that enable escape remain poorly understood. We elucidated
      genetic determinants underlying tumor escape in a transgenic mouse model of Wnt
      pathway-driven breast cancer, wherein targeted therapy is simulated by abrogating
      doxycycline-dependent Wnt1 transgene expression within established tumors. In
      mice with intact tumor suppressor pathways, tumors typically circumvented
      doxycycline withdrawal by reactivating Wnt signaling, either via aberrant
      (doxycycline-independent) Wnt1 transgene expression or via acquired somatic
      mutations in the gene encoding beta-catenin. Germline introduction of mutant
      tumor suppressor alleles into the model altered the timing and mode of tumor
      escape. Relapses occurring in the context of null Ink4a/Arf alleles (disrupting
      both the p16 Ink4a and p19 Arf tumor suppressors) arose quickly and rarely
      reactivated the Wnt pathway. In addition, Ink4a/Arf-deficient relapses resembled
      p53-deficient relapses in that both displayed morphologic and molecular hallmarks
      of an epithelial-to-mesenchymal transition (EMT). Notably, Ink4a/Arf deficiency
      promoted relapse in the absence of gross genomic instability. Moreover, Ink4a/Arf
      encoded proteins differed in their capacity to suppress oncogene independence.
      Isolated p19 Arf deficiency mirrored p53 deficiency in that both promoted rapid,
      EMT-associated mammary tumor escape, whereas isolated p16 Ink4a deficiency failed
      to accelerate relapse. Thus, p19 Arf/p53 pathway lesions may promote mammary
      cancer relapse even when inhibition of a targeted oncogenic signaling pathway
      remains in force.

PMID- 18060047
TI  - Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement
      therapy in parkinsonian mice.
AB  - Dopamine (DA) cell replacement therapy in Parkinson disease (PD) can be achieved
      using human fetal mesencephalic tissue; however, limited tissue availability has
      hindered further developments. Embryonic stem cells provide a promising
      alternative, but poor survival and risk of teratoma formation have prevented
      their clinical application. We present here a method for generating large numbers
      of DA neurons based on expanding and differentiating ventral midbrain (VM) neural
      stem cells/progenitors in the presence of key signals necessary for VM DA neuron
      development. Mouse VM neurospheres (VMNs) expanded with FGF2, differentiated with
      sonic hedgehog and FGF8, and transfected with Wnt5a (VMN-Wnt5a) generated 10-fold
      more DA neurons than did conventional FGF2-treated VMNs. VMN-Wnt5a cells
      exhibited the transcriptional and biochemical profiles and intrinsic
      electrophysiological properties of midbrain DA cells. Transplantation of these
      cells into parkinsonian mice resulted in significant cellular and functional
      recovery. Importantly, no tumors were detected and only a few transplanted grafts
      contained sporadic nestin-expressing progenitors. Our findings show that Wnt5a
      improves the differentiation and functional integration of stem cell-derived DA
      neurons in vivo and define Wnt5a-treated neural stem cells as an efficient and
      safe source of DA neurons for cell replacement therapy in PD.

PMID- 18060048
TI  - Heme oxygenase-1-derived carbon monoxide enhances the host defense response to
      microbial sepsis in mice.
AB  - Sepsis is characterized by a systemic response to severe infection. Although the
      inflammatory phase of sepsis helps eradicate the infection, it can have
      detrimental consequences if left unchecked. Therapy directed against inflammatory
      mediators of sepsis has shown little success and has the potential to impair
      innate antimicrobial defenses. Heme oxygenase-1 (HO-1) and the product of its
      enzymatic reaction, CO, have beneficial antiinflammatory properties, but little
      is known about their effects on microbial sepsis. Here, we have demonstrated that
      during microbial sepsis, HO-1-derived CO plays an important role in the
      antimicrobial process without inhibiting the inflammatory response. HO-1
      deficient mice suffered exaggerated lethality from polymicrobial sepsis.
      Targeting HO-1 to SMCs and myofibroblasts of blood vessels and bowel ameliorated
      sepsis-induced death associated with Enterococcus faecalis, but not Escherichia
      coli, infection. The increase in HO-1 expression did not suppress circulating
      inflammatory cells or their accumulation at the site of injury but did enhance
      bacterial clearance by increasing phagocytosis and the endogenous antimicrobial
      response. Furthermore, injection of a CO-releasing molecule into WT mice
      increased phagocytosis and rescued HO-1-deficient mice from sepsis-induced
      lethality. These data advocate HO-1-derived CO as an important mediator of the
      host defense response to sepsis and suggest CO administration as a possible
      treatment for the disease.

PMID- 18060049
TI  - High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive
      cytotoxic T-cells during the course of secondary dengue virus infection.
AB  - BACKGROUND: Dengue is one of the most important human diseases transmitted by an
      arthropod vector and the incidence of dengue virus infection has been increasing 
      over half the world's population now live in areas at risk of infection. Most
      infections are asymptomatic, but a subset of patients experience a potentially
      fatal shock syndrome characterised by plasma leakage. Severe forms of dengue are
      epidemiologically associated with repeated infection by more than one of the four
      dengue virus serotypes. Generally attributed to the phenomenon of antibody
      dependent enhancement, recent observations indicate that T-cells may also
      influence disease phenotype. METHODS AND FINDINGS: Virus-specific cytotoxic T
      lymphocytes (CTL) showing high level cross reactivity between dengue serotypes
      could be expanded from blood samples taken during the acute phase of secondary
      dengue infection. These could not be detected in convalescence when only CTL
      populations demonstrating significant serotype specificity were identified.
      Dengue cross-reactive CTL clones derived from these patients were of higher
      avidity than serotype-specific clones and produced much higher levels of both
      type 1 and certain type 2 cytokines, many previously implicated in dengue
      pathogenesis. CONCLUSION: Dengue serotype cross-reactive CTL clones showing high
      avidity for antigen produce higher levels of inflammatory cytokines than serotype
      specific clones. That such cells cannot be expanded from convalescent samples
      suggests that they may be depleted, perhaps as a consequence of activation
      induced cell death. Such high avidity cross-reactive memory CTL may produce
      inflammatory cytokines during the course of secondary infection, contributing to
      the pathogenesis of vascular leak. These cells appear to be subsequently deleted
      leaving a more serotype-specific memory CTL pool. Further studies are needed to
      relate these cellular observations to disease phenotype in a large group of
      patients. If confirmed they have significant implications for understanding the
      role of virus-specific CTL in pathogenesis of dengue disease.

PMID- 18060050
TI  - Dynamic perceptual changes in audiovisual simultaneity.
AB  - BACKGROUND: The timing at which sensory input reaches the level of conscious
      perception is an intriguing question still awaiting an answer. It is often
      assumed that both visual and auditory percepts have a modality specific
      processing delay and their difference determines perceptual temporal offset.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that the perception of audiovisual
      simultaneity can change flexibly and fluctuates over a short period of time while
      subjects observe a constant stimulus. We investigated the mechanisms underlying
      the spontaneous alternations in this audiovisual illusion and found that
      attention plays a crucial role. When attention was distracted from the stimulus,
      the perceptual transitions disappeared. When attention was directed to a visual
      event, the perceived timing of an auditory event was attracted towards that
      event. CONCLUSIONS/SIGNIFICANCE: This multistable display illustrates how
      flexible perceived timing can be, and at the same time offers a paradigm to
      dissociate perceptual from stimulus-driven factors in crossmodal feature binding.
      Our findings suggest that the perception of crossmodal synchrony depends on
      perceptual binding of audiovisual stimuli as a common event.

PMID- 18060052
TI  - On testing dependence between time to failure and cause of failure when causes of
      failure are missing.
AB  - The hypothesis of independence between the failure time and the cause of failure
      is studied by using the conditional probabilities of failure due to a specific
      cause given that there is no failure up to certain fixed time. In practice, there
      are situations when the failure times are available for all units but the causes
      of failures might be missing for some units. We propose tests based on U
      statistics to test for independence of the failure time and the cause of failure
      in the competing risks model when all the causes of failure cannot be observed.
      The asymptotic distribution is normal in each case. Simulation studies look at
      power comparisons for the proposed tests for two families of distributions. The
      one-sided and the two-sided tests based on Kendall type statistic perform
      exceedingly well in detecting departures from independence.

PMID- 18060053
TI  - Functional ablation of pRb activates Cdk2 and causes antiestrogen resistance in
      human breast cancer cells.
AB  - Estrogens are required for the proliferation of hormone dependent breast cancer
      cells, making estrogen receptor (ER) positive tumors amenable to endocrine
      therapies such as antiestrogens. However, resistance to these agents remains a
      significant cause of treatment failure. We previously demonstrated that
      inactivation of the retinoblastoma protein (pRb) family tumor suppressors causes
      antiestrogen resistance in MCF-7 cells, a widely studied model of estrogen
      responsive human breast cancers. In this study, we investigate the mechanism by
      which pRb inactivation leads to antiestrogen resistance. Cdk4 and cdk2 are two
      key cell cycle regulators that can phosphorylate and inactivate pRb, therefore we
      tested whether these kinases are required in cells lacking pRb function. pRb
      family members were inactivated in MCF-7 cells by expressing polyomavirus large
      tumor antigen (PyLT), and cdk activity was inhibited using the cdk inhibitors
      p16(INK4A) and p21(Waf1/Cip1). Cdk4 activity was no longer required in cells
      lacking functional pRb, while cdk2 activity was required for proliferation in
      both the presence and absence of pRb function. Using inducible PyLT cell lines,
      we further demonstrated that pRb inactivation leads to increased cyclin A
      expression, cdk2 activation and proliferation in antiestrogen arrested cells.
      These results demonstrate that antiestrogens do not inhibit cdk2 activity or
      proliferation of MCF-7 cells in the absence of pRb family function, and suggest
      that antiestrogen resistant breast cancer cells resulting from pRb pathway
      inactivation would be susceptible to therapies that target cdk2.

PMID- 18060051
TI  - Amyotrophic lateral sclerosis: an emerging era of collaborative gene discovery.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron
      disease (MND). It is currently incurable and treatment is largely limited to
      supportive care. Family history is associated with an increased risk of ALS, and
      many Mendelian causes have been discovered. However, most forms of the disease
      are not obviously familial. Recent advances in human genetics have enabled genome
      wide analyses of single nucleotide polymorphisms (SNPs) that make it possible to
      study complex genetic contributions to human disease. Genome-wide SNP analyses
      require a large sample size and thus depend upon collaborative efforts to collect
      and manage the biological samples and corresponding data. Public availability of
      biological samples (such as DNA), phenotypic and genotypic data further enhances
      research endeavors. Here we discuss a large collaboration among academic
      investigators, government, and non-government organizations which has created a
      public repository of human DNA, immortalized cell lines, and clinical data to
      further gene discovery in ALS. This resource currently maintains samples and
      associated phenotypic data from 2332 MND subjects and 4692 controls. This
      resource should facilitate genetic discoveries which we anticipate will
      ultimately provide a better understanding of the biological mechanisms of
      neurodegeneration in ALS.

PMID- 18060054
TI  - A novel and lethal de novo LQT-3 mutation in a newborn with distinct molecular
      pharmacology and therapeutic response.
AB  - BACKGROUND: SCN5A encodes the alpha-subunit (Na(v)1.5) of the principle Na(+)
      channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT
      syndrome (LQTS) variant 3 (LQT-3) in adults by disrupting inactivation of the
      Na(v)1.5 channel. Pharmacological targeting of mutation-altered Na(+) channels
      has proven promising in developing a gene-specific therapeutic strategy to manage
      specifically this LQTS variant. SCN5A mutations that cause similar channel
      dysfunction may also contribute to sudden infant death syndrome (SIDS) and other
      arrhythmias in newborns, but the prevalence, impact, and therapeutic management
      of SCN5A mutations may be distinct in infants compared with adults. METHODS AND
      RESULTS: Here, in a multidisciplinary approach, we report a de novo SCN5A
      mutation (F1473C) discovered in a newborn presenting with extreme QT prolongation
      and differential responses to the Na(+) channel blockers flecainide and
      mexiletine. Our goal was to determine the Na(+) channel phenotype caused by this
      severe mutation and to determine whether distinct effects of different Na(+)
      channel blockers on mutant channel activity provide a mechanistic understanding
      of the distinct therapeutic responsiveness of the mutation carrier. Sequence
      analysis of the proband revealed the novel missense SCN5A mutation (F1473C) and a
      common variant in KCNH2 (K897T). Patch clamp analysis of HEK 293 cells
      transiently transfected with wild-type or mutant Na(+) channels revealed
      significant changes in channel biophysics, all contributing to the proband's
      phenotype as predicted by in silico modeling. Furthermore, subtle differences in
      drug action were detected in correcting mutant channel activity that, together
      with both the known genetic background and age of the patient, contribute to the
      distinct therapeutic responses observed clinically. SIGNIFICANCE: The results of
      our study provide further evidence of the grave vulnerability of newborns to
      Na(+) channel defects and suggest that both genetic background and age are
      particularly important in developing a mutation-specific therapeutic personalized
      approach to manage disorders in the young.

PMID- 18060055
TI  - Effects of genetic mutations and chemical exposures on Caenorhabditis elegans
      feeding: evaluation of a novel, high-throughput screening assay.
AB  - BACKGROUND: Government agencies have defined a need to reduce, refine or replace
      current mammalian-based bioassays with testing methods that use alternative
      species. Invertebrate species, such as Caenorhabditis elegans, provide an
      attractive option because of their short life cycles, inexpensive maintenance,
      and high degree of evolutionary conservation with higher eukaryotes. The C.
      elegans pharynx is a favorable model for studying neuromuscular function, and the
      effects of chemicals on neuromuscular activity, i.e., feeding. Current feeding
      methodologies, however, are labor intensive and only semi-quantitative.
      METHODOLOGY/PRINCIPAL FINDINGS: Here a high-throughput assay is described that
      uses flow cytometry to measure C. elegans feeding by determining the size and
      intestinal fluorescence of hundreds of nematodes after exposure to fluorescent
      labeled microspheres. This assay was validated by quantifying fluorescence in
      feeding-defective C. elegans (eat mutants), and by exposing wild-type nematodes
      to the neuroactive compounds, serotonin and arecoline. The eat mutations
      previously determined to cause slow pumping rates exhibited the lowest feeding
      levels with our assay. Concentration-dependent increases in feeding levels after
      serotonin exposures were dependent on food availability, while feeding levels
      decreased in arecoline-exposed nematodes regardless of the presence of food. The
      effects of the environmental contaminants, cadmium chloride and chlorpyrifos, on
      wild-type C. elegans feeding were then used to demonstrate an application of the
      feeding assay. Cadmium exposures above 200 microM led to a sharp drop in feeding
      levels. Feeding of chlorpyrifos-exposed nematodes decreased in a concentration
      dependent fashion with an EC(50) of 2 microM. CONCLUSIONS/SIGNIFICANCE: The C.
      elegans fluorescence microsphere feeding assay is a rapid, reliable method for
      the assessment of neurotoxic effects of pharmaceutical drugs, industrial
      chemicals or environmental agents. This assay may also be applicable to large
      scale genetic or RNAi screens used to identify genes that are necessary for the
      development or function of the pharynx or other neuromuscular systems.

PMID- 18060057
TI  - Determinants of RNA quality from FFPE samples.
AB  - The large archives of formalin-fixed paraffin-embedded (FFPE) tissue specimens
      that exist are a highly valuable source of sample material for molecular
      biological analysis, including gene expression profiling. However, current data
      on adverse effects of standard pathological practice on the usefulness of
      biomolecular analytes obtained from such archived specimens is largely anecdotal.
      Here, we present a systematic examination of the most relevant parameters for
      integrity and useability of RNA obtained from FFPE samples, including storage
      time and conditions, fixation time, and specimen size. The results are
      particularly relevant for any application relying on cDNA synthesis as an initial
      step of the procedure, such as RT-PCR, and microarray analysis.

PMID- 18060056
TI  - HIV-infected children living in Central Africa have low persistence of antibodies
      to vaccines used in the Expanded Program on Immunization.
AB  - BACKGROUND: The Expanded Program on Immunization (EPI) is the most cost-effective
      measures to control vaccine-preventable diseases. Currently, the EPI schedule is
      similar for HIV-infected children; the introduction of antiretroviral therapy
      (ART) should considerably prolong their life expectancy. METHODS AND PRINCIPAL
      FINDINGS: To evaluate the persistence of antibodies to the EPI vaccines in HIV
      infected and HIV-exposed uninfected children who previously received these
      vaccines in routine clinical practice, we conducted a cross-sectional study of
      children, aged 18 to 36 months, born to HIV-infected mothers and living in
      Central Africa. We tested blood samples for antibodies to the combined
      diphtheria, tetanus, and whole-cell pertussis (DTwP), the measles and the oral
      polio (OPV) vaccines. We enrolled 51 HIV-infected children of whom 33 were
      receiving ART, and 78 HIV-uninfected children born to HIV-infected women. A lower
      proportion of HIV-infected children than uninfected children had antibodies to
      the tested antigens with the exception of the OPV types 1 and 2. This difference
      was substantial for the measles vaccine (20% of the HIV-infected children and 56%
      of the HIV-exposed uninfected children, p<0.0001). We observed a high risk of low
      antibody levels for all EPI vaccines, except OPV types 1 and 2, in HIV-infected
      children with severe immunodeficiency (CD4(+) T cells <25%). CONCLUSIONS AND
      SIGNIFICANCE: Children were examined at a time when their antibody concentrations
      to EPI vaccines would have still not undergone significant decay. However, we
      showed that the antibody concentrations were lowered in HIV-infected children.
      Moreover, antibody concentration after a single dose of the measles vaccine was
      substantially lower than expected, particularly low in HIV-infected children with
      low CD4(+) T cell counts. This study supports the need for a second dose of the
      measles vaccine and for a booster dose of the DTwP and OPV vaccines to maintain
      the antibody concentrations in HIV-infected and HIV-exposed uninfected children.

PMID- 18060058
TI  - Gene-centric characteristics of genome-wide association studies.
AB  - BACKGROUND: The high-throughput genotyping chips have contributed greatly to
      genome-wide association (GWA) studies to identify novel disease susceptibility
      single nucleotide polymorphisms (SNPs). The high-density chips are designed using
      two different SNP selection approaches, the direct gene-centric approach, and the
      indirect quasi-random SNPs or linkage disequilibrium (LD)-based tagSNPs
      approaches. Although all these approaches can provide high genome coverage and
      ascertain variants in genes, it is not clear to which extent these approaches
      could capture the common genic variants. It is also important to characterize and
      compare the differences between these approaches. METHODOLOGY/PRINCIPAL FINDINGS:
      In our study, by using both the Phase II HapMap data and the disease variants
      extracted from OMIM, a gene-centric evaluation was first performed to evaluate
      the ability of the approaches in capturing the disease variants in Caucasian
      population. Then the distribution patterns of SNPs were also characterized in
      genic regions, evolutionarily conserved introns and nongenic regions, ontologies
      and pathways. The results show that, no mater which SNP selection approach is
      used, the current high-density SNP chips provide very high coverage in genic
      regions and can capture most of known common disease variants under HapMap frame.
      The results also show that the differences between the direct and the indirect
      approaches are relatively small. Both have similar SNP distribution patterns in
      these gene-centric characteristics. CONCLUSIONS/SIGNIFICANCE: This study suggests
      that the indirect approaches not only have the advantage of high coverage but
      also are useful for studies focusing on various functional SNPs either in genes
      or in the conserved regions that the direct approach supports. The study and the
      annotation of characteristics will be helpful for designing and analyzing GWA
      studies that aim to identify genetic risk factors involved in common diseases,
      especially variants in genes and conserved regions.

PMID- 18060059
TI  - Time processing in Huntington's disease: a group-control study.
AB  - BACKGROUND: "Timing" processes are mediated via a disturbed neuronal network
      including the basal ganglia. Brain structures important for "timing" are also
      discussed to be critical for the deterioration of movements in Huntington's
      disease (HD). Changes in "timing processes" are found in HD, but no study has
      varied the degree of motor demands in timing functions in parallel in HD. It may
      be hypothesized that timing functions may be deteriorated to a different extent
      in motor and non-motor timing, because in motor timing the underlying brain
      structures may be more demanding than in non-motor timing. METHODOLOGY/PRINCIPLE
      FINDINGS: WE ASSESSED TIMING IN TWO DIFFERENT EXPERIMENTS: a time-estimation (TE)
      and a time-discrimination (TD) task. The demand on motor functions is high in the
      TE-task and low in the TD-task. Furthermore, general motor ability was assessed
      at different complexity levels. A presymptomatic (pHD), a symptomatic (HD) and a
      control group were investigated. We found a decline in timing functions when
      demands on the motor system were high (TE-task), in HD and even in pHD, compared
      to controls. In non-motor timing (TD task) and in the assessment of general motor
      ability, performance in the pHD-group was comparable to the controls and better
      than in the symptomatic group. Performance in both timing tasks was related to
      the duration until the estimated age of onset in pHDs. CONCLUSIONS/SIGNIFICANCE:
      The study shows a selective deterioration of time-estimation processes in
      symptomatic and even presymptomatic Huntington's disease. Time-discrimination
      processes were not affected in both patient groups. The relation of timing
      performance to the duration until the estimated age of onset in pHD is of
      clinical importance.

PMID- 18060060
TI  - Reporting science and conflicts of interest in the lay press.
AB  - BACKGROUND: Forthright reporting of financial ties and conflicts of interest of
      researchers is associated with public trust in and esteem for the scientific
      enterprise. METHODS/PRINCIPAL FINDINGS: We searched Lexis/Nexis Academic News for
      the top news stories in science published in 2004 and 2005. We conducted a
      content analysis of 1152 newspaper stories. Funders of the research were
      identified in 38% of stories, financial ties of the researchers were reported in
      11% of stories, and 5% reported financial ties of sources quoted. Of 73 stories
      not reporting on financial ties, 27% had financial ties publicly disclosed in
      scholarly journals. CONCLUSIONS/SIGNIFICANCE: Because science journalists often
      did not report conflict of interest information, adherence to gold-standard
      recommendations for science journalism was low. Journalists work under many
      different constraints, but nonetheless news reports of scientific research were
      incomplete, potentially eroding public trust in science.

PMID- 18060061
TI  - Oxygen reperfusion damage in an insect.
AB  - The deleterious effects of anoxia followed by reperfusion with oxygen in higher
      animals including mammals are well known. A convenient and genetically well
      characterized small-animal model that exhibits reproducible, quantifiable oxygen
      reperfusion damage is currently lacking. Here we describe the dynamics of whole
      organism metabolic recovery from anoxia in an insect, Drosophila melanogaster,
      and report that damage caused by oxygen reperfusion can be quantified in a novel
      but straightforward way. We monitored CO(2) emission (an index of mitochondrial
      activity) and water vapor output (an index of neuromuscular control of the
      spiracles, which are valves between the outside air and the insect's tracheal
      system) during entry into, and recovery from, rapid-onset anoxia exposure with
      durations ranging from 7.5 to 120 minutes. Anoxia caused a brief peak of CO(2)
      output followed by knock-out. Mitochondrial respiration ceased and the spiracle
      constrictor muscles relaxed, but then re-contracted, presumably powered by
      anaerobic processes. Reperfusion to sustained normoxia caused a bimodal re
      activation of mitochondrial respiration, and in the case of the spiracle
      constrictor muscles, slow inactivation followed by re-activation. After long
      anoxia durations, both the bimodality of mitochondrial reactivation and the
      recovery of spiracular control were impaired. Repeated reperfusion followed by
      episodes of anoxia depressed mitochondrial respiratory flux rates and damaged the
      integrity of the spiracular control system in a dose-dependent fashion. This is
      the first time that physiological evidence of oxygen reperfusion damage has been
      described in an insect or any invertebrate. We suggest that some of the
      traditional approaches of insect respiratory biology, such as quantifying
      respiratory water loss, may facilitate using D. melanogaster as a convenient,
      well-characterized experimental model for studying the underlying biology and
      mechanisms of ischemia and reperfusion damage and its possible mitigation.

PMID- 18060062
TI  - Repeated exposure to media violence is associated with diminished response in an
      inhibitory frontolimbic network.
AB  - BACKGROUND: Media depictions of violence, although often claimed to induce viewer
      aggression, have not been shown to affect the cortical networks that regulate
      behavior. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance
      imaging (fMRI), we found that repeated exposure to violent media, but not to
      other equally arousing media, led to both diminished response in right lateral
      orbitofrontal cortex (right ltOFC) and a decrease in right ltOFC-amygdala
      interaction. Reduced function in this network has been previously associated with
      decreased control over a variety of behaviors, including reactive aggression.
      Indeed, we found reduced right ltOFC responses to be characteristic of those
      subjects that reported greater tendencies toward reactive aggression.
      Furthermore, the violence-induced reduction in right ltOFC response coincided
      with increased throughput to behavior planning regions. CONCLUSIONS: These novel
      findings establish that even short-term exposure to violent media can result in
      diminished responsiveness of a network associated with behaviors such as reactive
      aggression.

PMID- 18060063
TI  - The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker
      of cellular aging in human skin.
AB  - Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare disorder
      characterized by accelerated aging and early death, frequently from stroke or
      coronary artery disease. 90% of HGPS cases carry the LMNA G608G (GGC>GGT)
      mutation within exon 11 of LMNA, activating a splice donor site that results in
      production of a dominant negative form of lamin A protein, denoted progerin.
      Screening 150 skin biopsies from unaffected individuals (newborn to 97 years)
      showed that a similar splicing event occurs in vivo at a low level in the skin at
      all ages. While progerin mRNA remains low, the protein accumulates in the skin
      with age in a subset of dermal fibroblasts and in a few terminally differentiated
      keratinocytes. Progerin-positive fibroblasts localize near the basement membrane
      and in the papillary dermis of young adult skin; however, their numbers increase
      and their distribution reaches the deep reticular dermis in elderly skin. Our
      findings demonstrate that progerin expression is a biomarker of normal cellular
      aging and may potentially be linked to terminal differentiation and senescence in
      elderly individuals.

PMID- 18060064
TI  - Expression of pyruvate carboxylase mRNA variants in liver of dairy cattle at
      calving.
AB  - BACKGROUND: Bovine liver expresses six pyruvate carboxylase (PC) transcript
      variants, bPC5'A, bPC5'B, bPC5'C, bPC5'D, bPC5'E, and bPC5'F, which only differ
      at the 5' untranslated region (UTR) and contain a common coding region. The
      objective of this experiment was to determine the profile and abundance of PC
      transcripts in bovine liver at calving. METHODOLOGY/PRINCIPAL FINDINGS: A
      ribonuclease protection assay (RPA) protocol was developed to simplify analysis
      of these variants and investigate the changes in abundance of each 5' UTR
      transcript relative to total PC mRNA. Liver biopsy samples collected from seven
      cows on +1 d relative to calving were analyzed by RPA to determine the profile in
      PC 5' UTR variants. Results show that all six bovine PC 5' UTR variants are
      detected at calving. Data indicate that bovine PC 5' UTR variant A is the most
      abundant, variants C and E are least abundant and expression of variants B, D and
      F is intermediate at calving. CONCLUSIONS: This manuscript describes a simplified
      RPA method that quantifies the abundance of six PC transcripts by using two
      riboprobes. The lack of uniformity in the pattern of PC 5' UTR variants at
      calving suggests an additional complexity for control of bovine PC mRNA
      expression at calving that may be the result of transcriptional controls,
      variation in mRNA processing, or a combination of these processes.

PMID- 18060065
TI  - Analysis of the neurotoxin complex genes in Clostridium botulinum A1-A4 and B1
      strains: BoNT/A3, /Ba4 and /B1 clusters are located within plasmids.
AB  - BACKGROUND: Clostridium botulinum and related clostridial species express
      extremely potent neurotoxins known as botulinum neurotoxins (BoNTs) that cause
      long-lasting, potentially fatal intoxications in humans and other mammals. The
      amino acid variation within the BoNT is used to categorize the species into seven
      immunologically distinct BoNT serotypes (A-G) which are further divided into
      subtypes. The BoNTs are located within two generally conserved gene arrangements
      known as botulinum progenitor complexes which encode toxin-associated proteins
      involved in toxin stability and expression. METHODOLOGY/PRINCIPAL FINDINGS:
      Because serotype A and B strains are responsible for the vast majority of human
      botulism cases worldwide, the location, arrangement and sequences of genes from
      eight different toxin complexes representing four different BoNT/A subtypes
      (BoNT/A1-Ba4) and one BoNT/B1 strain were examined. The bivalent Ba4 strain
      contained both the BoNT/A4 and BoNT/bvB toxin clusters. The arrangements of the
      BoNT/A3 and BoNT/A4 subtypes differed from the BoNT/A1 strains and were similar
      to those of BoNT/A2. However, unlike the BoNT/A2 subtype, the toxin complex genes
      of BoNT/A3 and BoNT/A4 were found within large plasmids and not within the
      chromosome. In the Ba4 strain, both BoNT toxin clusters (A4 and bivalent B) were
      located within the same 270 kb plasmid, separated by 97 kb. Complete genomic
      sequencing of the BoNT/B1 strain also revealed that its toxin complex genes were
      located within a 149 kb plasmid and the BoNT/A3 complex is within a 267 kb
      plasmid. CONCLUSIONS/SIGNIFICANCE: Despite their size differences and the BoNT
      genes they contain, the three plasmids containing these toxin cluster genes share
      significant sequence identity. The presence of partial insertion sequence (IS)
      elements, evidence of recombination/gene duplication events, and the discovery of
      the BoNT/A3, BoNT/Ba4 and BoNT/B1 toxin complex genes within plasmids illustrate
      the different mechanisms by which these genes move among diverse genetic
      backgrounds of C. botulinum.

PMID- 18060066
TI  - Multilineage potential of stable human mesenchymal stem cell line derived from
      fetal marrow.
AB  - Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs)
      and mesenchymal stem cells (MSCs). MSCs possess self-renewal capacity and
      pluripotency defined by their ability to differentiate into osteoblasts,
      chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate
      into neurons and glial cells in vitro, and in vivo following transplantation into
      the brain of animal models of neurological disorders including ischemia and
      intracerebral hemorrhage (ICH) stroke. In order to obtain sufficient number and
      homogeneous population of human MSCs, we have clonally isolated permanent and
      stable human MSC lines by transfecting primary cell cultures of fetal human bone
      marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines,
      HM3.B10 (B10), was found to differentiate into neural cell types including neural
      stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by
      expression of genetic markers for neural stem cells (nestin and Musashi1),
      neurons (neurofilament protein, synapsin and MAP2), astrocytes (glial fibrillary
      acidic protein, GFAP) and oligodendrocytes (myelin basic protein, MBP) as
      determined by RT-PCR assay. In addition, B10 cells were found to differentiate
      into neural cell types as shown by immunocytochical demonstration of nestin (for
      neural stem cells), neurofilament protein and beta-tubulin III (neurons) GFAP
      (astrocytes), and galactocerebroside (oligodendrocytes). Following brain
      transplantation in mouse ICH stroke model, B10 human MSCs integrate into host
      brain, survive, differentiate into neurons and astrocytes and induce behavioral
      improvement in the ICH animals. B10 human MSC cell line is not only a useful tool
      for the studies of organogenesis and specifically for the neurogenesis, but also
      provides a valuable source of cells for cell therapy studies in animal models of
      stroke and other neurological disorders.

PMID- 18060068
TI  - A genomic background based method for association analysis in related
      individuals.
AB  - BACKGROUND: Feasibility of genotyping of hundreds and thousands of single
      nucleotide polymorphisms (SNPs) in thousands of study subjects have triggered the
      need for fast, powerful, and reliable methods for genome-wide association
      analysis. Here we consider a situation when study participants are genetically
      related (e.g. due to systematic sampling of families or because a study was
      performed in a genetically isolated population). Of the available methods that
      account for relatedness, the Measured Genotype (MG) approach is considered the
      'gold standard'. However, MG is not efficient with respect to time taken for the
      analysis of genome-wide data. In this context we proposed a fast two-step method
      called Genome-wide Association using Mixed Model and Regression (GRAMMAR) for the
      analysis of pedigree-based quantitative traits. This method certainly overcomes
      the drawback of time limitation of the measured genotype (MG) approach, but pays
      in power. One of the major drawbacks of both MG and GRAMMAR, is that they
      crucially depend on the availability of complete and correct pedigree data, which
      is rarely available. METHODOLOGY: In this study we first explore type 1 error and
      relative power of MG, GRAMMAR, and Genomic Control (GC) approaches for genetic
      association analysis. Secondly, we propose an extension to GRAMMAR i.e. GRAMMAR
      GC. Finally, we propose application of GRAMMAR-GC using the kinship matrix
      estimated through genomic marker data, instead of (possibly missing and/or
      incorrect) genealogy. CONCLUSION: Through simulations we show that MG approach
      maintains high power across a range of heritabilities and possible pedigree
      structures, and always outperforms other contemporary methods. We also show that
      the power of our proposed GRAMMAR-GC approaches to that of the 'gold standard' MG
      for all models and pedigrees studied. We show that this method is both feasible
      and powerful and has correct type 1 error in the context of genome-wide
      association analysis in related individuals.

PMID- 18060067
TI  - Depolarization-evoked secretion requires two vicinal transmembrane cysteines of
      syntaxin 1A.
AB  - BACKGROUND: The interactions of the voltage-gated Ca(2+) channel (VGCC) with
      syntaxin 1A (Sx 1A), Synaptosome-associated protein of 25 kD (SNAP-25), and
      synaptotagmin, couple electrical excitation to evoked secretion. Two vicinal Cys
      residues, Cys 271 and Cys 272 in the Sx 1A transmembrane domain, are highly
      conserved and participate in modulating channel kinetics. Each of the Sx1A Cys
      mutants, differently modify the kinetics of Cav1.2, and neuronal Cav2.2 calcium
      channel. METHODOLOGY/PRINCIPLE FINDINGS: We examined the effects of various Sx1A
      Cys mutants and the syntaxin isoforms 2, 3, and 4 each of which lack vicinal Cys
      residues, on evoked secretion, monitoring capacitance transients in a functional
      release assay. Membrane capacitance in Xenopus oocytes co-expressing Cav1.2,
      Sx1A, SNAP-25 and synaptotagmin, which is Bot C- and Bot A-sensitive, was
      elicited by a double 500 ms depolarizing pulse to 0 mV. The evoked-release was
      obliterated when a single Cys Sx1A mutant or either one of the Sx isoforms were
      substituted for Sx 1A, demonstrating the essential role of vicinal Cys residues
      in the depolarization mediated process. Protein expression and confocal imaging
      established the level of the mutated proteins in the cell and their targeting to
      the plasma membrane. CONCLUSIONS/SIGNIFICANCE: We propose a model whereby the two
      adjacent transmembranal Cys residues of Sx 1A, lash two calcium channels.
      Consistent with the necessity of a minimal fusion complex termed the excitosome,
      each Sx1A is in a complex with SNAP-25, Syt1, and the Ca(2+) channel. A Hill
      coefficient >2 imply that at least three excitosome complexes are required for
      generating a secreting hetero-oligomer protein complex. This working model
      suggests that a fusion pore that opens during membrane depolarization could be
      lined by alternating transmembrane segments of Sx1A and VGCC. The functional
      coupling of distinct amino acids of Sx 1A with VGCC appears to be essential for
      depolarization-evoked secretion.

PMID- 18060069
TI  - Structure of the scientific community modelling the evolution of resistance.
AB  - Faced with the recurrent evolution of resistance to pesticides and drugs, the
      scientific community has developed theoretical models aimed at identifying the
      main factors of this evolution and predicting the efficiency of resistance
      management strategies. The evolutionary forces considered by these models are
      generally similar for viruses, bacteria, fungi, plants or arthropods facing drugs
      or pesticides, so interaction between scientists working on different biological
      organisms would be expected. We tested this by analysing co-authorship and co
      citation networks using a database of 187 articles published from 1977 to 2006
      concerning models of resistance evolution to all major classes of pesticides and
      drugs. These analyses identified two main groups. One group, led by ecologists or
      agronomists, is interested in agricultural crop or stock pests and diseases. It
      mainly uses a population genetics approach to model the evolution of resistance
      to insecticidal proteins, insecticides, herbicides, antihelminthic drugs and
      miticides. By contrast, the other group, led by medical scientists, is interested
      in human parasites and mostly uses epidemiological models to study the evolution
      of resistance to antibiotic and antiviral drugs. Our analyses suggested that
      there is also a small scientific group focusing on resistance to antimalaria
      drugs, and which is only poorly connected with the two larger groups. The
      analysis of cited references indicates that each of the two large communities
      publishes its research in a different set of literature and has its own keystone
      references: citations with a large impact in one group are almost never cited by
      the other. We fear the lack of exchange between the two communities might slow
      progress concerning resistance evolution which is currently a major issue for
      society.

PMID- 18060070
TI  - Infectious offspring: how birds acquire and transmit an avian polyomavirus in the
      wild.
AB  - Detailed patterns of primary virus acquisition and subsequent dispersal in wild
      vertebrate populations are virtually absent. We show that nestlings of a songbird
      acquire polyomavirus infections from larval blowflies, common nest ectoparasites
      of cavity-nesting birds, while breeding adults acquire and renew the same viral
      infections via cloacal shedding from their offspring. Infections by these DNA
      viruses, known potential pathogens producing disease in some bird species,
      therefore follow an 'upwards vertical' route of an environmental nature mimicking
      horizontal transmission within families, as evidenced by patterns of viral
      infection in adults and young of experimental, cross-fostered offspring. This
      previously undescribed route of viral transmission from ectoparasites to
      offspring to parent hosts may be a common mechanism of virus dispersal in many
      taxa that display parental care.

PMID- 18060071
TI  - Patterns of genome evolution among the microsporidian parasites Encephalitozoon
      cuniculi, Antonospora locustae and Enterocytozoon bieneusi.
AB  - BACKGROUND: Microsporidia are intracellular parasites that are highly-derived
      relatives of fungi. They have compacted genomes and, despite a high rate of
      sequence evolution, distantly related species can share high levels of gene order
      conservation. To date, only two species have been analysed in detail, and data
      from one of these largely consists of short genomic fragments. It is therefore
      difficult to determine how conservation has been maintained through
      microsporidian evolution, and impossible to identify whether certain regions are
      more prone to genomic stasis. PRINCIPAL FINDINGS: Here, we analyse three large
      fragments of the Enterocytozoon bieneusi genome (in total 429 kbp), a species of
      medical significance. A total of 296 ORFs were identified, annotated and their
      context compared with Encephalitozoon cuniculi and Antonospora locustae. Overall,
      a high degree of conservation was found between all three species, and
      interestingly the level of conservation was similar in all three pairwise
      comparisons, despite the fact that A. locustae is more distantly related to E.
      cuniculi and E. bieneusi than either are to each other. CONCLUSIONS/SIGNIFICANCE:
      Any two genes that are found together in any pair of genomes are more likely to
      be conserved in the third genome as well, suggesting that a core of genes tends
      to be conserved across the entire group. The mechanisms of rearrangments
      identified among microsporidian genomes were consistent with a very slow
      evolution of their architecture, as opposed to the very rapid sequence evolution
      reported for these parasites.

PMID- 18060072
TI  - A virosomal malaria peptide vaccine elicits a long-lasting sporozoite-inhibitory
      antibody response in a phase 1a clinical trial.
AB  - OBJECTIVES: Peptides delivered on the surface of influenza virosomes have been
      shown to induce solid humoral immune responses in experimental animals. High
      titers of peptide-specific antibodies were also induced in a phase 1a clinical
      trial in volunteers immunized with virosomal formulations of two peptides derived
      from the circumsporozoite protein (CSP) and the apical membrane antigen 1 (AMA-1)
      of Plasmodium falciparum. The main objective of this study was to perform a
      detailed immunological and functional analysis of the CSP-specific antibodies
      elicited in this phase 1a trial. METHODOLOGY/PRINCIPAL FINDINGS: 46 healthy
      malaria-naive adults were immunized with virosomal formulations of two peptide
      phosphatidylethanolamine conjugates, one derived from the NANP repeat region of
      P. falciparum CSP (designated UK-39) the other from P. falciparum AMA-1
      (designated AMA49-C1). The two antigens were delivered in two different
      concentrations, alone and in combination. One group was immunized with empty
      virosomes as control. In this report we show a detailed analysis of the antibody
      response against UK-39. Three vaccinations with a 10 microg dose of UK-39 induced
      high titers of sporozoite-binding antibodies in all volunteers. This IgG response
      was affinity maturated and long-lived. Co-administration of UK-39 and AMA49-C1
      loaded virosomes did not interfere with the immunogenicity of UK-39. Purified
      total IgG from UK-39 immunized volunteers inhibited sporozoite migration and
      invasion of hepatocytes in vitro. Sporozoite inhibition closely correlated with
      titers measured in immunogenicity assays. CONCLUSIONS: Virosomal delivery of a
      short, conformationally constrained peptide derived from P. falciparum CSP
      induced a long-lived parasite-inhibitory antibody response in humans. Combination
      with a second virosomally-formulated peptide derived from P. falciparum AMA-1 did
      not interfere with the immunogenicity of either peptide, demonstrating the
      potential of influenza virosomes as a versatile, human-compatible antigen
      delivery platform for the development of multivalent subunit vaccines. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00400101.

PMID- 18060073
TI  - Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines:
      implications for therapy.
AB  - BACKGROUND: Among gynecologic cancers, ovarian cancer is the second most common
      and has the highest death rate. Cancer is a genetic disorder and arises due to
      the accumulation of somatic mutations in critical genes. An understanding of the
      genetic basis of ovarian cancer has implications both for early detection and for
      therapeutic intervention in this population of patients. METHODOLOGY/PRINCIPAL
      FINDINGS: Fifteen ovarian cancer cell lines, commonly used for in vitro
      experiments, were screened for mutations using bidirectional direct sequencing in
      all coding regions of BRAF, MEK1 and MEK2. BRAF mutations were identified in four
      of the fifteen ovarian cancer cell lines studied. Together, these four cell lines
      contained four different BRAF mutations, two of which were novel. ES-2 had the
      common B-Raf p.V600E mutation in exon 15 and Hey contained an exon 11 missense
      mutation, p.G464E. The two novel B-Raf mutants identified were a 5 amino acid
      heterozygous deletion p.N486-P490del in OV90, and an exon 4 missense substitution
      p.Q201H in OVCAR 10. One of the cell lines, ES-2, contained a mutation in MEK1,
      specifically, a novel heterozygous missense substitution, p.D67N which resulted
      from a nt 199 G-->A transition. None of the cell lines contained coding region
      mutations in MEK2. Functional characterization of the MEK1 mutant p.D67N by
      transient transfection with subsequent Western blot analysis demonstrated
      increased ERK phosphorylation as compared to controls. CONCLUSIONS/SIGNIFICANCE:
      In this study, we report novel BRAF mutations in exon 4 and exon 12 and also
      report the first mutation in MEK1 associated with human cancer. Functional data
      indicate the MEK1 mutation may confer alteration of activation through the MAPK
      pathway. The significance of these findings is that BRAF and MEK1/2 mutations may
      be more common than anticipated in ovarian cancer which could have important
      implications for treatment of patients with this disease and suggests potential
      new therapeutic avenues.

PMID- 18060074
TI  - The genotype specific competitive ability does not correlate with infection in
      natural Daphnia magna populations.
AB  - BACKGROUND: Different evolutionary hypotheses predict a correlation between the
      fitness of a genotype in the absence of infection and the likelihood to become
      infected. The cost of resistance hypothesis predicts that resistant genotypes pay
      a cost of being resistant and are less fit in the absence of parasites. The
      inbreeding-infection hypothesis predicts that the susceptible individuals are
      less fit due to inbreeding depression. METHODS AND RESULTS: Here we tested if a
      host's natural infection status was associated with its fitness. First, we
      experimentally confirmed that cured but formerly infected Daphnia magna are
      genetically more susceptible to reinfections with Octosporea bayeri than
      naturally uninfected D. magna. We then collected from each of 22 populations both
      uninfected and infected D. magna genotypes. All were treated against parasites
      and kept in their asexual phase. We estimated their relative fitness in an
      experiment against a tester genotype and in another experiment in direct
      competition. Consistently, we found no difference in competitive abilities
      between uninfected and cured but formerly infected genotypes. This was the case
      both in the presence as well as in the absence of sympatric parasites during the
      competition trials. CONCLUSIONS: Our data do not support the inbreeding-infection
      hypothesis. They also do not support a cost of resistance, however ignoring other
      parasite strains or parasite species. We suggest as a possible explanation for
      our results that resistance genes might segregate largely independently of other
      fitness associated genes in this system.

PMID- 18060075
TI  - Effects of blood collection conditions on ovarian cancer serum markers.
AB  - BACKGROUND: Evaluating diagnostic and early detection biomarkers requires
      comparing serum protein concentrations among biosamples ascertained from subjects
      with and without cancer. Efforts are generally made to standardize blood
      processing and storage conditions for cases and controls, but blood sample
      collection conditions cannot be completely controlled. For example, blood samples
      from cases are often obtained from persons aware of their diagnoses, and
      collected after fasting or in surgery, whereas blood samples from some controls
      may be obtained in different conditions, such as a clinic visit. By measuring the
      effects of differences in collection conditions on three different markers, we
      investigated the potential of these effects to bias validation studies.
      METHODOLOGY AND PRINCIPLE FINDINGS: We analyzed serum concentrations of three
      previously studied putative ovarian cancer serum biomarkers-CA 125, Prolactin and
      MIF-in healthy women, women with ovarian cancer undergoing gynecologic surgery,
      women undergoing surgery for benign ovary pathology, and women undergoing surgery
      with pathologically normal ovaries. For women undergoing surgery, a blood sample
      was collected either in the clinic 1 to 39 days prior to surgery, or on the day
      of surgery after anesthesia was administered but prior to the surgical procedure,
      or both. We found that one marker, prolactin, was dramatically affected by
      collection conditions, while CA 125 and MIF were unaffected. Prolactin levels
      were not different between case and control groups after accounting for the
      conditions of sample collection, suggesting that sample ascertainment could
      explain some or all of the previously reported results about its potential as a
      biomarker for ovarian cancer. CONCLUSIONS: Biomarker validation studies should
      use standardized collection conditions, use multiple control groups, and/or
      collect samples from cases prior to influence of diagnosis whenever feasible to
      detect and correct for potential biases associated with sample collection.

PMID- 18060076
TI  - Neglected tropical diseases, neglected data sources, and neglected issues.
AB  - BACKGROUND: Lymphatic filariasis (LF) is a so-called neglected tropical disease,
      currently overshadowed by higher-profile efforts to address malaria,
      tuberculosis, and HIV/AIDS. Despite recent successes in arresting transmission,
      some 40 million people who already have the disease have been largely neglected.
      This study aims to increase understanding of how this vulnerable, neglected group
      can be helped. METHODS: We used purposive sampling to select 60 men and women
      with filarial lymphoedema (45 with filarial elephantiasis and 15 men with
      filarial hydrocoele) from the south of Sri Lanka in 2004-2005. Participants were
      selected to give a balance of men and women and poor and nonpoor, and a range of
      stages of the disease. Participants' experiences and the consequences of their
      disease for the household were explored with in-depth qualitative, semistructured
      interviews. FINDINGS: LF was extremely debilitating to participants over long
      periods of time. The stigma attached to the condition caused social isolation and
      emotional distress, and delayed diagnosis and treatment, resulting in undue
      advancement of the disease. Free treatment services at government clinics were
      avoided because the participants' condition would be identifiable in public. Loss
      of income due to the condition was reported by all households in the sample, not
      just the poorest. Households that were already on low incomes were pushed into
      near destitution, from which it was almost impossible to escape. Affected members
      of low-income households also had less opportunity to obtain appropriate
      treatment from distant clinics, and had living and working conditions that made
      hygiene and compliance difficult. SIGNIFICANCE: This highly vulnerable category
      of patients has low visibility, thus becoming marginalized and forgotten. With an
      estimated 300,000 total cases of elephantiasis and/or oedema in Sri Lanka, and
      around 300,000 men with filarial hydrocoele, the affected households will need
      help and support for many years to come. These individuals should be specially
      targeted for identification, outreach, and care. The global strategy for
      elimination is aimed at the cessation of transmission, but there will remain some
      40 million individuals with clinical manifestations whose needs and problems are
      illustrated in this study.

PMID- 18060077
TI  - Measuring the burden of neglected tropical diseases: the global burden of disease
      framework.
AB  - Reliable, comparable information about the main causes of disease and injury in
      populations, and how these are changing, is a critical input for debates about
      priorities in the health sector. Traditional sources of information about the
      descriptive epidemiology of diseases, injuries, and risk factors are generally
      incomplete, fragmented, and of uncertain reliability and comparability. The
      Global Burden of Disease (GBD) study has provided a conceptual and methodological
      framework to quantify and compare the health of populations using a summary
      measure of both mortality and disability, the disability-adjusted life year
      (DALY).This paper describes key features of the Global Burden of Disease analytic
      approach, which provides a standardized measurement framework to permit
      comparisons across diseases and injuries, as well as risk factors, and a
      systematic approach to the evaluation of data. The paper describes the evolution
      of the GBD, starting from the first study for the year 1990, summarizes the
      methodological improvements incorporated into GBD revisions for the years 2000
      2004 carried out by the World Health Organization, and examines priorities and
      issues for the next major GBD study, funded by the Bill & Melinda Gates
      Foundation, and commencing in 2007.The paper presents an overview of summary
      results from the Global Burden of Disease study 2002, with a particular focus on
      the neglected tropical diseases, and also an overview of the comparative risk
      assessment for 26 global risk factors. Taken together, trypanosomiasis, Chagas
      disease, schistosomiasis, leishmaniasis, lymphatic filariasis, onchocerciasis,
      intestinal nematode infections, Japanese encephalitis, dengue, and leprosy
      accounted for an estimated 177,000 deaths worldwide in 2002, mostly in sub
      Saharan Africa, and about 20 million DALYs, or 1.3% of the global burden of
      disease and injuries. Further research is currently underway to revise and update
      these estimates.

PMID- 18060078
TI  - Measuring neglect.

PMID- 18060079
TI  - Sequence-based typing of leptospira: epidemiology in the genomic era.

PMID- 18060080
TI  - Neglected patients with a neglected disease? A qualitative study of lymphatic
      filariasis.
AB  - BACKGROUND: Lymphatic filariasis (LF) is a so-called neglected tropical disease,
      currently overshadowed by higher-profile efforts to address malaria,
      tuberculosis, and HIV/AIDS. Despite recent successes in arresting transmission,
      some 40 million people who already have the disease have been largely neglected.
      This study aims to increase understanding of how this vulnerable, neglected group
      can be helped. METHODS: We used purposive sampling to select 60 men and women
      with filarial lymphoedema (45 with filarial elephantiasis and 15 men with
      filarial hydrocoele) from the south of Sri Lanka in 2004-2005. Participants were
      selected to give a balance of men and women and poor and nonpoor, and a range of
      stages of the disease. Participants' experiences and the consequences of their
      disease for the household were explored with in-depth qualitative, semistructured
      interviews. FINDINGS: LF was extremely debilitating to participants over long
      periods of time. The stigma attached to the condition caused social isolation and
      emotional distress, and delayed diagnosis and treatment, resulting in undue
      advancement of the disease. Free treatment services at government clinics were
      avoided because the participants' condition would be identifiable in public. Loss
      of income due to the condition was reported by all households in the sample, not
      just the poorest. Households that were already on low incomes were pushed into
      near destitution, from which it was almost impossible to escape. Affected members
      of low-income households also had less opportunity to obtain appropriate
      treatment from distant clinics, and had living and working conditions that made
      hygiene and compliance difficult. SIGNIFICANCE: This highly vulnerable category
      of patients has low visibility, thus becoming marginalized and forgotten. With an
      estimated 300,000 total cases of elephantiasis and/or oedema in Sri Lanka, and
      around 300,000 men with filarial hydrocoele, the affected households will need
      help and support for many years to come. These individuals should be specially
      targeted for identification, outreach, and care. The global strategy for
      elimination is aimed at the cessation of transmission, but there will remain some
      40 million individuals with clinical manifestations whose needs and problems are
      illustrated in this study.

PMID- 18060081
TI  - A schistosomiasis research agenda.
AB  - There is a long and rich history of research and control in the field of
      schistosomiasis that has resulted in major scientific and public health
      accomplishments. Examples of such findings and accomplishments include
      immunologic regulation in chronic infections, the association of helminth
      infections with Th1-regulating Th2-type immune responses, the critical role of
      interleukin-13 in fibrogenesis, and the development and validation of the "dose
      pole" for determining praziquantel dosages in the field. Perhaps in part because
      of this broad and successful history, those who work on schistosomiasis come from
      a wide variety of backgrounds and interests. While such variety is enriching to
      the field, it sometimes results in diverse opinions about which of the many
      research opportunities should be pursued. Such diversity, we believe, has at
      times led to a divisiveness that has harmed overall progress in the field. Partly
      in response to such events, we have worked with as many of those interested in
      schistosomiasis as we could identify to develop what we feel is a comprehensive
      and cohesive agenda for schistosomiasis research.

PMID- 18060082
TI  - Optimization of topical therapy for Leishmania major localized cutaneous
      leishmaniasis using a reliable C57BL/6 Model.
AB  - BACKGROUND: Because topical therapy is easy and usually painless, it is an
      attractive first-line option for the treatment of localized cutaneous
      leishmaniasis (LCL). Promising ointments are in the final stages of development.
      One main objective was to help optimize the treatment modalities of human LCL
      with WR279396, a topical formulation of aminoglycosides that was recently proven
      to be efficient and safe for use in humans. METHODOLOGY/PRINCIPAL FINDINGS:
      C57BL/6 mice were inoculated in the ear with luciferase transgenic L. major and
      then treated with WR279396. The treatment period spanned lesion onset, and the
      evolution of clinical signs and bioluminescent parasite loads could be followed
      for several months without killing the mice. As judged by clinical healing and a
      1.5-3 log parasite load decrease in less than 2 weeks, the 94% efficacy of 10
      daily applications of WR279396 in mice was very similar to what had been
      previously observed in clinical trials. When WR279396 was applied with an
      occlusive dressing, parasitological and clinical efficacy was significantly
      increased and no rebound of parasite load was observed. In addition, 5
      applications under occlusion were more efficient when done every other day for 10
      days than daily for 5 days, showing that length of therapy is a more important
      determinant of treatment efficacy than the total dose topically applied.
      CONCLUSIONS/SIGNIFICANCE: Occlusion has a significant adjuvant effect on
      aminoglycoside ointment therapy of experimental cutaneaous leishmaniasis (CL), a
      concept that might apply to other antileishmanial or antimicrobial ointments.
      Generated in a laboratory mouse-based model that closely mimics the course of LCL
      in humans, our results support a schedule based on discontinuous applications for
      a few weeks rather than several daily applications for a few days.

PMID- 18060083
TI  - Nifurtimox plus Eflornithine for late-stage sleeping sickness in Uganda: a case
      series.
AB  - BACKGROUND: We report efficacy and safety outcomes from a prospective case series
      of 31 late-stage T.b. gambiense sleeping sickness (Human African Trypanosomiasis,
      HAT) patients treated with a combination of nifurtimox and eflornithine (N+E) in
      Yumbe, northwest Uganda in 2002-2003, following on a previously reported
      terminated trial in nearby Omugo, in which 17 patients received the combination
      under the same conditions. METHODOLOGY/PRINCIPAL FINDINGS: Eligible sequential
      late-stage patients received 400 mg/Kg/day eflornithine (Ornidyl, Sanofi-Aventis)
      for seven days plus 15 mg/Kg/day (20 mg for children <15 years old) nifurtimox
      (Lampit, Bayer AG) for ten days. Efficacy (primary outcome) was monitored for 24
      months post discharge. Clinical and laboratory adverse events (secondary outcome)
      were monitored during treatment. All 31 patients were discharged alive, but two
      died post-discharge of non-HAT and non-treatment causes, and one was lost to
      follow-up. Efficacy ranged from 90.3% to 100.0% according to analysis approach.
      Five patients experienced major adverse events during treatment, and neutropenia
      was common (9/31 patients). CONCLUSIONS/SIGNIFICANCE: Combined with the previous
      group of 17 trial patients, this case series yields a group of 48 patients
      treated with N+E, among whom no deaths judged to be treatment- or HAT-related, no
      treatment terminations and no relapses have been noted, a very favourable outcome
      in the context of late-stage disease. N+E could be the most promising combination
      regimen available for sleeping sickness, and deserves further evaluation.

PMID- 18060084
TI  - Functional and structural insights revealed by molecular dynamics simulations of
      an essential RNA editing ligase in Trypanosoma brucei.
AB  - RNA editing ligase 1 (TbREL1) is required for the survival of both the insect and
      bloodstream forms of Trypanosoma brucei, the parasite responsible for the
      devastating tropical disease African sleeping sickness. The type of RNA editing
      that TbREL1 is involved in is unique to the trypanosomes, and no close human
      homolog is known to exist. In addition, the high-resolution crystal structure
      revealed several unique features of the active site, making this enzyme a
      promising target for structure-based drug design. In this work, two 20 ns
      atomistic molecular dynamics (MD) simulations are employed to investigate the
      dynamics of TbREL1, both with and without the ATP substrate present. The
      flexibility of the active site, dynamics of conserved residues and crystallized
      water molecules, and the interactions between TbREL1 and the ATP substrate are
      investigated and discussed in the context of TbREL1's function. Differences in
      local and global motion upon ATP binding suggest that two peripheral loops,
      unique to the trypanosomes, may be involved in interdomain signaling events.
      Notably, a significant structural rearrangement of the enzyme's active site
      occurs during the apo simulations, opening an additional cavity adjacent to the
      ATP binding site that could be exploited in the development of effective
      inhibitors directed against this protozoan parasite. Finally, ensemble averaged
      electrostatics calculations over the MD simulations reveal a novel putative RNA
      binding site, a discovery that has previously eluded scientists. Ultimately, we
      use the insights gained through the MD simulations to make several predictions
      and recommendations, which we anticipate will help direct future experimental
      studies and structure-based drug discovery efforts against this vital enzyme.

PMID- 18060085
TI  - Eliminating lymphatic filariasis, onchocerciasis, and schistosomiasis from the
      americas: breaking a historical legacy of slavery.

PMID- 18060086
TI  - Detection of Schistosoma mansoni eggs in feces through their interaction with
      paramagnetic beads in a magnetic field.
AB  - BACKGROUND: Diagnosis of intestinal schistosomiasis in low endemic areas is a
      problem because often control measures have reduced egg burdens in feces to below
      the detection limits of classical coproparasitological methods. Evaluation of
      molecular methods is hindered by the absence of an established standard with
      maximum sensitivity and specificity. One strategy to optimize method performance,
      where eggs are rare events, is to examine large amounts of feces. A novel
      diagnostic method for isolation of Schistosoma mansoni eggs in feces, and an
      initial evaluation of its performance is reported here. METHODOLOGY/PRINCIPAL
      FINDINGS: Known amounts of S. mansoni eggs were seeded into 30 g of normal human
      feces and subjected to a sequence of spontaneous sedimentation, sieving, Ritchie
      method, incubation and isolation through interaction with paramagnetic beads.
      Preliminary tests demonstrated the efficacy of lectins as ligands, but they also
      indicated that the paramagnetic beads alone were sufficient to isolate the eggs
      under a magnetic field through an unknown mechanism. Eggs were identified by
      microscopic inspection, with a sensitivity of 100% at 1.3 eggs per gram of feces
      (epg). Sensitivity gradually decreased to 25% at a concentration of 0.1 epg. In a
      preliminary application of the new method to the investigation of a recently
      established focus in southern Brazil, approximately 3 times more eggs were
      detected than with the thick-smear Kato-Katz method. CONCLUSIONS/SIGNIFICANCE:
      The novel S. mansoni detection method may significantly improve diagnosis of
      infections with low burdens in areas of recent introduction of the parasite,
      areas under successful control of transmission, or in infected travelers. It may
      also improve the evaluation of new treatments and vaccines.

PMID- 18060087
TI  - Cost-effectiveness of blood agar for isolation of mycobacteria.
AB  - BACKGROUND: Mycobacterium species are grown using specific media that increase
      laboratory cost, thus hampering their diffusion in resource-limited countries.
      Preliminary data suggested that versatile blood agar may be also used for
      mycobacterial culture. METHODOLOGY: We examined the growth of 41 different
      Mycobacterium species on 5% blood agar. Over a 24-month period we analysed
      isolation of mycobacteria after parallel inoculation of clinical specimens into
      both a reference automated system (BACTEC 9000 MB broth) and 5% blood agar slant
      tubes, after NaOH decontamination, and compared the cost of performing 1,000
      analyses using these two techniques. CONCLUSIONS: Mycobacterium reference species
      cultured on blood agar, with the exception of Mycobacterium ulcerans. Inoculation
      of 1,634 specimens yielded 95 Mycobacterium isolates. Blood agar performed
      significantly more efficiently than BACTEC 9000 MB broth (94 vs 88 isolates, P =
      0.03). Decontamination of Candida albicans in 5 specimens by addition of
      amphotericin B in blood agar yielded one more M. tuberculosis isolate that could
      not be isolated in BACTEC broth. Uneven distribution of time to culture
      positivity for M. tuberculosis had a median (range) of 19+/-5 days using blood
      agar and 26+/-6 days using BACTEC 9000 MB broth. Cost for 1,000 analyses in
      France was estimated to be of 1,913 euros using the blood agar method and 8,990
      euros using the BACTEC 9000 MB method. Blood agar should be regarded as a first
      line medium for culturing Mycobacterium species. It saves time, is cost
      effective, is more sensitive than, and at least as rapid as the automated method.
      This is of particular importance for resource-limited countries in which the
      prevalence of tuberculosis is high.

PMID- 18060088
TI  - Enhanced Leishmania braziliensis infection following pre-exposure to sandfly
      saliva.
AB  - BACKGROUND: Sand fly saliva has an array of pharmacological and immunomodulatory
      components, and immunity to saliva protects against Leishmania infection. In the
      present study, we have studied the immune response against Lutzomyia intermedia
      saliva, the main vector of Leishmania braziliensis in Brazil, and the effects of
      saliva pre-exposure on L. braziliensis infection employing an intradermal
      experimental model. METHODOLOGY/PRINCIPAL FINDINGS: BALB/c mice immunized with L.
      intermedia salivary gland sonicate (SGS) developed a saliva-specific antibody
      response and a cellular immune response with presence of both IFN-gamma and IL-4.
      The inflammatory infiltrate observed in SGS-immunized mice was comprised of
      numerous polymorphonuclear and few mononuclear cells. Mice challenged with live
      L. braziliensis in the presence of saliva were not protected although lesion
      development was delayed. The inoculation site and draining lymph node showed
      continuous parasite replication and low IFN-gamma to IL-4 ratio, indicating that
      pre-exposure to L. intermedia saliva leads to modulation of the immune response.
      Furthermore, in an endemic area of cutaneous leishmaniasis, patients with active
      lesions displayed higher levels of anti-L. intermedia saliva antibodies when
      compared to individuals with a positive skin test result for Leishmania.
      CONCLUSION: These results show that pre-exposure to sand fly saliva plays an
      important role in the outcome of cutaneous leishmaniasis, in both mice and
      humans. They emphasize possible hurdles in the development of vaccines based on
      sand fly saliva and the need to identify and select the individual salivary
      candidates instead of using whole salivary mixture that may favor a non
      protective response.

PMID- 18060089
TI  - Host gene expression profiling of dengue virus infection in cell lines and
      patients.
AB  - BACKGROUND: Despite the seriousness of dengue-related disease, with an estimated
      50-100 million cases of dengue fever and 250,000-500,000 cases of dengue
      hemorrhagic fever/dengue shock syndrome each year, a clear understanding of
      dengue pathogenesis remains elusive. Because of the lack of a disease model in
      animals and the complex immune interaction in dengue infection, the study of host
      response and immunopathogenesis is difficult. The development of genomics
      technology, microarray and high throughput quantitative PCR have allowed
      researchers to study gene expression changes on a much broader scale. We
      therefore used this approach to investigate the host response in dengue virus
      infected cell lines and in patients developing dengue fever.
      METHODOLOGY/PRINCIPAL FINDINGS: Using microarray and high throughput quantitative
      PCR method to monitor the host response to dengue viral replication in cell line
      infection models and in dengue patient blood samples, we identified
      differentially expressed genes along three major pathways; NF-kappaB initiated
      immune responses, type I interferon (IFN) and the ubiquitin proteasome pathway.
      Among the most highly upregulated genes were the chemokines IP-10 and I-TAC, both
      ligands of the CXCR3 receptor. Increased expression of IP-10 and I-TAC in the
      peripheral blood of ten patients at the early onset of fever was confirmed by
      ELISA. A highly upregulated gene in the IFN pathway, viperin, was overexpressed
      in A549 cells resulting in a significant reduction in viral replication. The
      upregulation of genes in the ubiquitin-proteasome pathway prompted the testing of
      proteasome inhibitors MG-132 and ALLN, both of which reduced viral replication.
      CONCLUSION/SIGNIFICANCE: Unbiased gene expression analysis has identified new
      host genes associated with dengue infection, which we have validated in
      functional studies. We showed that some parts of the host response can be used as
      potential biomarkers for the disease while others can be used to control dengue
      viral replication, thus representing viable targets for drug therapy.

PMID- 18060090
TI  - Substance Abuse Treatment Providers' Referral to Self-Help: Review and Future
      Empirical Directions.
AB  - As duration and intensity of services decline, the treatment system's success in
      engaging substance-using clients in self-help (SH) will increasingly influence
      client outcomes. Clinicians play an important role in involving clients with SH,
      yet little is known about how referral decisions are made or about the referral
      process itself. This paper reviews clinicians' attitudes toward SH and their role
      in referring clients to SH, and identifies types of research needed to elucidate
      the referral process from both clinicians' and clients' perspectives. Such
      research can help enhance the number and outcome of referrals to self-help
      groups.

PMID- 18060091
TI  - A randomized controlled trial to assess the efficacy of tiotropium in Canadian
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who smoke
      have a greater annual rate of decline in forced expiratory volume in 1 s (FEV(1))
      than those patients who have stopped smoking. OBJECTIVES: To assess the effect of
      tiotropium on pre-dose (trough) FEV(1) in patients with COPD followed in Canada.
      METHODS: A total of 913 patients were randomly assigned to receive either
      tiotropium 18 mug once daily (n=608) or placebo (usual care minus inhaled
      anticholinergics) (n=305) for 48 weeks in the present randomized, double-blind,
      parallel-group study. The effect of tiotropium on measurements of lung function
      (FEV(1), FEV(6) and forced vital capacity), symptoms, health-related quality of
      life (St George's Respiratory Questionnaire) and exacerbations were examined.
      RESULTS: Tiotropium improved trough FEV(1) in both current and ex-smokers
      compared with placebo. Baseline FEV(1) in smokers and ex-smokers was 1.03 L and
      0.93 L, respectively (P<0.001). At week 48, the mean difference between the
      tiotropium and placebo groups was 0.14+/-0.04 L (P<0.001) in the smoker group and
      0.08+/-0.02 L (P<0.0001) in the ex-smoker group. Tiotropium also significantly
      improved trough forced vital capacity and FEV(6) compared with placebo throughout
      the treatment period (P<0.05, for all). Furthermore, tiotropium significantly
      improved the St George's Respiratory Questionnaire total score compared with
      placebo at week 48 (40.9 versus 43.7 units, P<0.005). CONCLUSIONS: Compared with
      the placebo group, tiotropium provides sustained improvements in lung function in
      patients with COPD, with improvements for smokers and ex-smokers.

PMID- 18060092
TI  - Comparative efficacy of two doses of nebulized colistimethate in the eradication
      of Pseudomonas aeruginosa in children with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) affects the respiratory and digestive systems.
      It evolves toward deterioration of pulmonary function through colonization with
      Pseudomonas aeruginosa. There is no consensus with respect to its eradication.
      Nebulized colistimethate is used for eradication treatment, but the optimal dose
      and duration is yet to be determined. OBJECTIVES: To compare the efficacy of two
      doses of nebulized colistimethate (30 mg versus 75 mg twice daily) for the
      eradication of P aeruginosa in children with CF and intermittent colonization.
      METHODS: A cohort study with both historical (30 mg) and prospective (75 mg) arms
      was conducted from 1999 to 2003. Medical records were used to collect data.
      RESULTS: Eighty-one patients were recruited in the retrospective group, for a
      total of 111 treatment courses. Twenty patients were recruited in the prospective
      group, for a total of 20 events. There was no statistically significant
      difference in the rate of eradication of P aeruginosa at days 28 and 90, neither
      when comparing the doses of colistimethate nor duration of treatment. There was a
      statistically significant difference (P=0.004) between days 1 and 90 in all
      analyzed subgroups (regardless of dose or duration of treatment) for forced vital
      capacity only. In the group of patients in whom eradication was achieved at day
      28 (after receiving a three-week treatment course of colistimethate), 50% of
      patients developed a new infection 5.75 months later, on average, regardless of
      the dose administered. In the group of patients who achieved eradication at day
      90 (after receiving a 15-week treatment course of colistimethate), 50% of the 14
      patients developed a new infection after an average period of 7.3 months
      (P=0.28). CONCLUSIONS: There is no difference in the efficacy between a 30 mg
      dose and a 75 mg dose of colistimethate for P aeruginosa eradication in children
      with CF and intermittent colonization.

PMID- 18060093
TI  - Playing cards on asthma management: a new interactive method for knowledge
      transfer to primary care physicians.
AB  - OBJECTIVES: To describe an interactive playing card workshop in the communication
      of asthma guidelines recommendations, and to assess the initial evaluation of
      this educational tool by family physicians. DESIGN: Family physicians were
      invited to participate in the workshop by advertisements or personal contacts.
      Each physician completed a standardized questionnaire on his or her perception of
      the rules, content and properties of the card game. SETTING: A university-based
      continuing medical education initiative. PARTICIPANTS: Primary care physicians.
      MAIN OUTCOME MEASURES: Physicians' evaluation of the rules, content and
      usefulness of the program. RESULTS: The game allowed the communication of
      relevant asthma-related content, as well as experimentation with a different
      learning format. It also stimulated interaction in a climate of friendly
      competition. Participating physicians considered the method to be an innovative
      tool that facilitated reflection, interaction and learning. It generated relevant
      discussions on how to apply guideline recommendations to current asthma care.
      CONCLUSIONS: This new, interactive, educational intervention, integrating play
      and scientific components, was well received by participants. This method may be
      of value to help integrate current guidelines into current practice, thus
      facilitating knowledge transfer to caregivers.

PMID- 18060094
TI  - Mortality of elderly patients in Ontario after hospital admission for chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with
      significant mortality. It is currently the fourth leading cause of death in
      Canada and the world. OBJECTIVES: To describe the mortality of elderly patients
      in Ontario after hospital admission for COPD. METHODS: A retrospective cohort
      study was conducted using the Discharge Abstract Database from the Canadian
      Institute for Health Information. Patients aged 65 years and older who were
      admitted to hospital between 2001 and 2004 with primary discharge diagnoses
      labelled with International Classification of Diseases, Ninth Revision codes 491,
      492 and 496 were included in the study. RESULTS: Mortality rates were 8.81,
      12.10, 14.53 and 27.72 per 100 COPD hospital admissions at 30, 60, 90 and 365
      days after hospital discharge, respectively. Mortality also increased with age,
      and men had higher rates than women. No significant differences in mortality
      rates were found between different socioeconomic groups (P>0.05). Patients with
      shared care of a family physician or general practitioner and a specialist had
      significantly lower mortality rates than the overall rate (P<0.05), and their
      rates were approximately one-half the rate of patients with only one physician.
      CONCLUSIONS: Hospitalization with COPD is associated with significant mortality.
      Patients who were cared for by both a family physician or general practitioner
      and a specialist had significantly lower mortality rates than those cared for by
      only one physician, suggesting that continuous and coordinated care results in
      better survival.

PMID- 18060095
TI  - Two sisters with idiopathic pulmonary hemosiderosis.
AB  - Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar
      hemorrhage with unknown etiology. In the present report, the presentations of two
      sisters are described: one sister had IPH, eosinophilia and a high serum
      immunoglobulin E (IgE) level; and the other had IPH, pneumothorax, eosinophilia
      and a high serum IgE level. Both cases had quite unusual presentations. The first
      patient was 23 years of age, and had suffered from dry cough and progressive
      dyspnea for four years. Her hemoglobin level was 60 g/L, total serum IgE level
      was 900 U/mL and eosinophilia was 9%. Her chest radiography revealed diffuse
      infiltration. She died due to respiratory failure. The second patient was 18
      years of age. She had also suffered from dry cough and gradually increasing
      dyspnea for two years. She had partial pneumothorax in the right lung and diffuse
      infiltration in other pulmonary fields on chest radiography. Her hemoglobin level
      was 99 g/L, total serum IgE level was 1200 U/mL and eosinophilia was 8%. IPH was
      diagnosed by open lung biopsy. All these findings suggested that familial or
      allergic factors, as well as immunological factors, might have contributed to the
      etiology of IPH.

PMID- 18060097
TI  - Missed opportunities for the secondary prevention of cardiovascular disease in
      Canada.
AB  - BACKGROUND: Strong evidence supports the use of antithrombotic agents
      (antiplatelets or oral anticoagulants), statins and angiotensin-converting enzyme
      inhibitors in patients with atherosclerotic cardiovascular disease; beta-blockers
      are additionally indicated in patients with coronary artery disease. OBJECTIVES:
      The investigators sought to determine the extent to which guideline-recommended
      treatments and target goals are adopted in ambulatory patients with
      cardiovascular disease in Canada. METHODS: Two large, prospective, community
      based registries (the Vascular Protection Registry and the Guideline Oriented
      Approach to Lipid Lowering Registry) enrolled 9809 outpatients with coronary
      artery disease, cerebrovascular disease, peripheral vascular disease or multiple
      cardiovascular risk factors from primary care settings in nine provinces across
      Canada between 2001 and 2004. This analysis focused primarily on patients with
      cardiovascular disease (n=6296). RESULTS: At baseline, antithrombotics, statins
      and angiotensin-converting enzyme inhibitors were used in 92%, 80% and 57% of
      patients, respectively; beta-blockers were used in 59% of patients with coronary
      artery disease. The dosing of most drug therapies was suboptimal compared with
      guideline-recommended dosing derived from clinical trials. Treatment goals for
      cardiovascular risk factors were suboptimally attained: low-density lipoprotein
      cholesterol in 50% of patients, total to high-density lipoprotein cholesterol
      ratio in 51% of patients, systolic and diastolic blood pressure in 58% and 78% of
      patients, respectively, and waist circumference and body mass index in 45% and
      19%, respectively. CONCLUSIONS: These data suggest specific opportunities for
      improving the care of patients with cardiovascular disease in Canada. The focus
      must now shift from awareness of treatment gaps to implementation of effective
      solutions.

PMID- 18060098
TI  - Cocaine-related acute aortic dissection: patient demographics and clinical
      outcomes.
AB  - BACKGROUND: To compare the demographics, inpatient mortality and short-term
      survival following hospital discharge between cocaine-using and non-cocaine-using
      patients presenting with acute aortic dissection. METHODS: Retrospective analysis
      of 46 consecutive patients admitted with the diagnosis of acute aortic dissection
      at the Mount Sinai Hospital (Chicago, USA) between 1996 and 2005. Among these 46
      patients, cocaine use was temporally related to the presenting symptom in 13
      patients (28%, group 1). Patients who were not cocaine users were grouped into
      group 2 (33 patients [72%]). RESULTS: Patients in group 1 were younger than those
      in group 2 (mean age 38+/-9 years versus 63+/-17 years, P=0.001), more likely to
      be smokers (13 of 13 patients [100%] versus 15 of 33 patients [45%], P=0.001) and
      had a higher prevalence of accelerated hypertension (mean blood pressure 210/130
      mmHg) compared with group 2 (10 of 13 patients [77%] versus 11 of 33 patients
      [33%]) (P=0.01). Group 1 patients had a higher prevalence of type B dissection
      than group 2 (nine of 13 patients [69%] versus one of 33 patients [3%]). After
      hospital discharge, eight of 13 patients (62%) in the cocaine group continued to
      use cocaine. Mortality following hospital discharge was significantly higher in
      cocaine users (nine of 13 patients [69%]) compared with the non-cocaine users
      (four of 33 patients [12%], P=0.01). Recurrent dissection was the cause of death
      in five of the 13 deaths (42%) in the cocaine group. CONCLUSIONS: Patients
      presenting with acute aortic dissection temporally related to cocaine use are
      more likely to be younger, smokers, have higher prevalence of hypertensive
      crises, more likely to have type B aortic dissection and may have a higher
      mortality following hospital discharge, possibly due to continued cocaine use and
      recurrent aortic dissection.

PMID- 18060099
TI  - Heart rate recovery--a potential marker of clinical outcomes in heart failure
      patients receiving beta-blocker therapy.
AB  - BACKGROUND: Heart rate recovery (HRR) within the first few minutes of graded
      exercise has been associated with impaired clinical outcomes in patients being
      evaluated for coronary artery disease. HRR is abnormal in patients with heart
      failure (HF), but has not been associated with clinical outcomes in these
      patients. The objective of the present study was to determine whether HRR
      following cardiopulmonary exercise testing (CPET) correlates with peak oxygen
      consumption (VO(2)), and whether it impacts clinical outcomes, including HF
      hospitalizations and total mortality, or the need for cardiac transplantation.
      METHODS: CPET was performed in 78 patients referred to the Montreal Heart
      Institute (Montreal, Quebec) with congestive HF between January 2000 and December
      2002. All patients had New York Heart Association class II or III HF with a left
      ventricular ejection fraction of 45% or lower. Mean (+/- SD) age was 53+/-11
      years and left ventricular ejection fraction was 27+/-9%. Forty-four per cent had
      ischemic cardiomyopathy, 88% received beta-blockers and 79% received angiotensin
      converting enzyme inhibitors. HRR was defined as the difference from peak
      exercise HR to HR measured at specific time intervals. HRR was calculated 30 s,
      60 s, 90 s and 120 s after exercise. RESULTS: Mean peak VO(2) was 18.0+/-5.3
      mL/kg/min, resting HR was 74+/-13 beats/min and peak HR was 119+/-22 beats/min.
      HRR measured was 10+/-9 beats/min after 30 s, 20+/-12 beats/min after 60 s, 25+/
      15 beats/min after 90 s and 30+/-13 beats/min after 120 s. At 90 s, patients with
      an HRR below 24 beats/min were more likely to have an HF hospitalization at five
      year follow-up (eight hospitalizations [22.2%] versus two hospitalizations
      [2.7%]; P=0.0134). There was a correlation between peak VO(2) and HRR 90 s and
      120 s after completion of the exercise test (r=0.40 after 90 s, P=0.001, and
      r=0.41 after 120 s, P=0.008). CONCLUSIONS: In patients with HF, blunted HRR 90 s
      and 120 s after CPET correlate with peak VO(2) and are associated with increased
      risk of worsening HF. HRR is easily measured and a useful marker for morbidity in
      patients with HF.

PMID- 18060100
TI  - Potential shift from coronary bypass surgery to percutaneous coronary
      intervention for multivessel disease and its economic impact in the drug-eluting
      stent era.
AB  - BACKGROUND: Drug-eluting stents (DES) may promote percutaneous coronary
      intervention (PCI) procedures in patients traditionally referred for coronary
      artery bypass graft (CABG) surgery and may save money. OBJECTIVES: The purpose of
      the present study was to quantify the potential shift from CABG surgery to
      multivessel PCI in the DES era and to model the economic consequences. METHODS:
      Based on predefined criteria, the feasibility of PCI was evaluated in patients
      with multivessel coronary artery disease who underwent CABG surgery before the
      availability of DES at the Centre Hospitalier de l'Universite de Montreal's Notre
      Dame Hospital (Montreal, Quebec). Modelling was used to evaluate the potential
      cost savings using multivessel PCI instead of CABG surgery. Equal one-year
      outcomes in both groups were assumed, with the exception of a 10% repeat
      revascularization (RR) rate in the DES group and a 4% RR rate in the CABG group.
      The impact of those assumptions was evaluated using 1000 Monte Carlo simulations.
      RESULTS: The authors retrospectively evaluated that, of 289 patients who
      underwent CABG without concomitant valve surgery between January and December
      2003, only 22 patients (8%) were good candidates for multivessel DES
      implantation. The procedures would have involved an average of 3.6 DES per
      patient. The average cost per revascularization procedure was $14,402 with
      surgery and $11,220 for multivessel DES implantation (using $2,200 DES), leading
      to a savings of $3,182 per patient. However, after including RR procedures, PCI
      would only have been associated with savings of $812 per surgery avoided. Monte
      Carlo analysis revealed that surgery may be less expensive than PCI in 36% of
      patients. CONCLUSIONS: Most patients who underwent CABG surgery in 2003 were
      retrospectively judged to be ineligible for multivessel PCI with DES. In the rare
      eligible patient, multivessel PCI with DES is not expected to produce savings to
      health care costs in Canada unless the DES purchase cost continues to decrease.

PMID- 18060102
TI  - Acute pulmonary edema following pericardiocentesis for cardiac tamponade.
AB  - Pericardiocentesis for therapeutic drainage of pericardial fluid may be
      associated with a variety of complications, including laceration of the right
      ventricle or coronary artery, arrhythmias, viscus perforation, hypotension,
      pneumothorax, adult respiratory distress syndrome and death. Hemodynamic
      derangements such as acute left ventricular failure, pulmonary edema and
      cardiogenic shock are infrequent and, hence, less well recognized. The present
      report describes a patient with pericardial effusion and tamponade who developed
      cardiogenic shock requiring inotropic support shortly following uncomplicated
      ultrasound-guided pericardial drainage.

PMID- 18060101
TI  - Arterialization of a vein graft promotes cell cycle progression through Akt and
      p38 mitogen-activated protein kinase pathways: impact of the preparation
      procedure.
AB  - BACKGROUND: Vein arterialization following bypass surgery often leads to graft
      occlusion, but the underlying cellular mechanisms have been poorly studied.
      OBJECTIVES: Cell cycle progression and the activation of proliferation signalling
      were compared in arterialized grafts prepared either according to the
      conventional procedure or using pharmacological relaxation with the native vein.
      METHODS: Using the porcine carotid-jugular bilateral interposition graft model on
      one side, a segment of porcine jugular vein was prepared for grafting using the
      conventional procedure, with pressure distention at 300 mmHg; the segment grafted
      on the other side was treated with a combination of pharmacological vasodilators.
      Both veins were grafted into the carotid artery for two weeks. RESULTS: On the
      immunolabelling of proliferation cell nuclear antigen, a greater number of
      proliferating cells was found in the conventionally prepared grafts compared with
      pharmacologically prepared grafts. Cyclin D1 expression and phosphorylation of
      retinoblastoma increased after implantation, coinciding with nuclear accumulation
      of beta-catenin, activation of the Akt and mitogen-activated protein kinase
      cascades, and upregulated phosphatase and tensin homologue phosphorylation.
      Replacement of distention with pharmacological relaxation reduced the increase in
      cyclin D1 expression, phosphorylation of retinoblastoma, Akt-Thr(308), glycogen
      synthase kinase 3 beta and p38, but not extracellular signal-regulated kinases.
      This technique preserved the active phosphatase and tensin homologue, as well as
      the expression of cyclin-dependent kinase inhibitor p21(Cip1), while elevating
      the expression of p27(Kip1). CONCLUSIONS: It was concluded that two-week arterial
      implantation stimulates proliferation signalling and promotes the cell cycle in
      vein grafts. Replacement of the conventional preparation procedures with
      pharmacological vasorelaxation restricts the activation of proliferation and cell
      cycle progression, and can be beneficial for improving vein graft patency.

PMID- 18060103
TI  - Pheochromocytoma associated with apical-sparing left ventricular dysfunction due
      to acute afterload mismatch: a novel clinical entity?
AB  - The case of a patient with pheochromocytoma who presented with an unusual pattern
      of left ventricular dysfunction not previously described is reported. Although a
      triad of headaches, sweating attacks and palpitations is generally recognized as
      the classic mode of presentation of this pathology, this patient first presented
      with shock and pulmonary edema. Moreover, both echocardiography and angiography
      showed severe basal and mid-ventricular left ventricular dysfunction but
      preserved apical contractility. This hitherto unidentified finding was
      interpreted as being due to an afterload mismatch, rather than to an intrinsic
      myocardial injury, as is usually reported in such cases.

PMID- 18060104
TI  - Surgical strategies for severe calcification of the aorta (porcelain aorta) in
      two patients with homozygous familial hypercholesterolemia.
AB  - Homozygous familial hypercholesterolemia (HzFH) is a rare genetic defect caused
      predominantly by mutations at the low-density lipoprotein receptor. Until recent
      advances in the management of this complex disorder, patients affected by HzFH
      rarely survived beyond 30 years of age. Two patients with HzFH who survived to
      adulthood and developed cardiovascular complications requiring surgery are
      reported. In these patients, a porcelain aorta complicated surgical management.
      Lipid profile, mutational analysis and pathological assessment of the aorta were
      performed in two patients referred for cardiac surgery. The first patient was a
      46-year-old man with a history of coronary artery bypass grafting (CABG) and
      recurrent severe angina who, because of a heavily calcified ascending aorta,
      required a complex repeat CABG. The second patient was a 42-year-old woman who
      underwent CAGB at 28 years of age and presented 13 years later with aortic
      stenosis. The extensive calcifications of the whole aortic root required
      performance of a modified Cabrol procedure. A porcelain aorta appears to be a
      feature of HzFH. This has an important impact on surgical planning and management
      and on possible pathophysiological processes related to the cardiovascular
      complications of HzFH.

PMID- 18060105
TI  - Hypertrophic cardiomyopathy involving the right ventricular apex.

PMID- 18060106
TI  - Acute myocardial infarction caused by late stent thrombosis associated with
      progressive incomplete stent apposition.

PMID- 18060107
TI  - Design of organometallic group IV heteroallylic complexes and their catalytic
      properties for polymerizations and olefin centered transformations.
AB  - The use of metallocenes in many stoichiometric and catalytic processes has been
      the impetus for the development of new organometallic complexes, especially those
      containing early transition metals. The formation of coordinative unsaturated
      complexes using allylic, benzamidinate and aminopyridine families is presented.
      The synthesis and structural parameters of the new complexes, their activation
      and use in the polymerization of alpha-olefins and dienes, in the dehydrogenative
      coupling of silanes and in the hydroamination reactions comprise the objectives
      of this review.

PMID- 18060108
TI  - Templated assembly of a mu6-CO3 2- dodecanuclear lanthanum dibenzoylmethanide
      hydroxido cluster with concomitant formation of phenylglyoxylate.
AB  - Reaction of LaCl(3) and dibenzoylmethane (Ph(2)acacH) in methanol with an excess
      of triethylamine resulted in the unexpected formation of a dodecanuclear hydroxo
      bridged La cluster templated by CO(3)(2-) and phenylglyoxylate (Phgly), as
      determined by X-ray crystallography.

PMID- 18060109
TI  - Bis(di-2-pyridyl-methanediol)copper(II) dihydrogentrifluoride: a structural and
      spectroscopic study of the H2F3 - anion in a complex salt.
AB  - The H(2)F(3)(-) anion in mononuclear [Cu(dpd)(2)][(H(2)F(3))(2)] (dpd = di-2
      pyridyl-methanediol) exists as a HF(2)(-)/HF adduct as evidenced by infrared
      spectroscopy and X-ray crystallography.

PMID- 18060110
TI  - Dendronized scorpionate complexes of molybdenum in low and high oxidation states.
AB  - Tridentate (L(3)) and bidentate (L(2)) poly(pyrazolyl)methane ligands (Gn
      dend)OCH(2)C(pz)(3) (1-4) and (Gn-dend)CH(3,5-Me(2)pz)(2) (pz = pyrazol-1-yl)
      have been used to synthesize the molybdenum(0) complexes [Mo(CO)(3)(L(3))] (G0
      G3, 5-8), [Mo(CO)(4)(L(2))] (G0-G1, 13-14), and [Mo(CO)(3)(NCMe)(L(2))] (G0, 15),
      and the molybdenum(VI) complexes [MoCl(2)O(2)(L(2))] (9-12). The G0-G3 prefixes
      represent the generation of poly(aryl ether) dendrons in which the metal
      complexes are embedded. The molecular structures of compounds 13 and 15 have been
      determined by X-ray diffraction studies and the hydrodynamic radii of tricarbonyl
      complexes 5-8 calculated by diffusion-ordered NMR spectroscopy (DOSY).
      Molybdenum(VI) compounds 9-12 have also been evaluated as catalysts for olefin
      epoxidation, showing comparable but inferior performances than ligand-free
      MoCl(2)O(2), probably because of the labile coordination of L(2).

PMID- 18060111
TI  - Residual and exploitable fluorescence in micellar self-assembled ON-OFF sensors
      for copper(II).
AB  - A set of new ligands, L2H(2)-L5H(2), containing the 1,4,8,11-tetraaza-5,7-dione
      framework has been prepared, The ligands feature lipophilic substituents either
      on the carbon atom in the 6 position or on the amino groups, or on both. The
      solution behaviour of the ligands when included in TritonX-100 micelles has been
      investigated by means of potentiometric titrations and protonation and
      complexation constants for the Cu(2+) cation have been determined in micellar
      medium. Micellar assemblies containing the ligands and pyrene have been prepared,
      and coupled pH-metric and fluorimetric titrations allowed the determination of
      the response of the systems as ON-OFF fluorescent sensors for Cu(2+). A
      correlation between the effective lipophilicity of the ligand and the residual
      fluorescence (i.e. the fluorescence of the OFF state) was observed, and with the
      more lipophilic ligand, L3H(2), we obtained a residual fluorescence as low as 8%,
      with a significant improvement with respect to other published systems. On the
      other hand, introduction of functionalities on the amino groups of 1,4,8,11
      tetraaza-5,7-dione brings the drawback of a small but significant decrease of the
      exploitable fluorescence, i.e. the fluorescence of the system in the absence of
      added Cu(2+), at the pH value suitable for full metal complexation.

PMID- 18060112
TI  - Oxidative cleavage of tetraaryltetraphosphane-1,4-diides by nickel(II) and
      palladium(II): formation of unusual Ni(0) and Pd(0) diaryldiphosphene complexes.
AB  - [Na(2)(thf)(4)(P(4)Mes(4))] (1) (Mes = 2,4,6-Me(3)C(6)H(2)) reacts with one
      equivalent of [NiCl(2)(PEt(3))(2)], [NiCl(2)(PMe(2)Ph)(2)],
      [PdCl(2)(PBu(n)(3))(2)] or [PdCl(2)(PMe(2)Ph)(2)] to give the corresponding
      nickel(0) and palladium(0) dimesityldiphosphene complexes [Ni(eta(2)
      P(2)Mes(2))(PEt(3))(2)] (2), [Ni(eta(2)-P(2)Mes(2))(PMe(2)Ph)(2)] (3), [Pd(eta(2)
      P(2)Mes(2))(PBu(n)(3))(2)] (4) and [Pd(eta(2)-P(2)Mes(2))(PMe(2)Ph)(2)] (5),
      respectively, via a redox reaction. The molecular structures of the diphosphene
      complexes 2-5 are described.

PMID- 18060113
TI  - Reaction and subsequent transformation of anionic acetylide-carbene complexes
      using the Ph3PAu+ fragment.
AB  - The metallated Fischer-type carbene complexes (CO)(5)M=C(NMe(2))C[triple bond]CLi
      (M = Cr, W) react with Ph(3)PAuNO(3) to form the beta-substituted products
      (CO)(5)M=C(NMe(2))C[triple bond]CAuPPh(3). In solution these products isomerise
      by formal metal fragment exchange to furnish Ph(3)PAuC(=NMe(2))C[triple
      bond]CM(CO)(5). A preliminary kinetic investigation by means of (1)H-NMR
      spectroscopy indicates an unusual and complicated reaction mechanism. Model DFT
      calculations predict small energy differences between the products before and
      after the metal fragment exchange.

PMID- 18060114
TI  - Reactivity and stability of platinum(II) formyl complexes based on PCP-type
      ligands. The significance of sterics.
AB  - The synthesis and characterization of several Pt(ii) complexes, including formyl
      complexes, based on the PCP-type pincer ligands C(6)H(4)[CH(2)P(iPr)(2)](2)
      ((iPr)PCP) and C(6)H(4)[CH(2)P(tBu)(2)](2) ((tBu)PCP) are described. The chloride
      complex ((iPr)PCP)PtCl (6) and the unsaturated cationic complexes [(PCP)Pt](+)X(
      ) (X = OTf(-), BF(4)(-)) (1, 7), based on both PCP ligands, were prepared and the
      latter reacted with carbon monoxide to give the corresponding cationic carbonyl
      complexes [(PCP)Pt(CO)](+)X(-) (X = OTf(-), BF(4)(-)) (2, 8a). Hydride
      nucleophilic attack on both carbonyl complexes resulted in rare neutral platinum
      formyl complexes ((iPr)PCP)Pt(CHO) (3) and ((tBu)PCP)Pt(CHO) (9). Complex 3
      undergoes decarbonylation to the corresponding hydride complex within hours at
      room temperature, while the bulkier complex 9 is more stable and undergoes
      complete decarbonylation only after 3-4 d. This observation demonstrates the very
      significant steric effect of the ligand on stabilization of the corresponding
      formyl complexes. Reaction of complex 9 with triflic acid resulted in the
      carbonyl complex [((tBu)PCP)Pt(CO)](+) OTf(-) (8b) with liberation of H(2), an
      unusual transformation for a metal formyl. Reaction with methyl triflate resulted
      in the Fischer carbene-type complex, the methoxy-methylidene
      [((tBu)PCP)Pt(CHOCH(3))](+)OTf(-) (11). The X-ray structures of complexes 2, 6,
      8a and 11 were determined.

PMID- 18060115
TI  - Dinuclear PCP pincer complexes from Lewis acidic [Pd(OTf)(PCP)] and basic [Pd(4
      Spy)(PCP)] (OTf = triflate; 4-Spy = 4-pyridinethiolate; PCP = (
      )CH(CH(2)CH(2)PPh(2))(2)).
AB  - The Lewis acidic pincer with a labile triflate ligand, viz. [Pd(OTf)(PCP)] (PCP =
      (-)CH(CH(2)CH(2)PPh(2))(2)) was prepared from [PdCl(PCP)] with AgOTf. It reacts
      readily with neutral bidentate ligands [L = 4,4'-bipyridine (4,4'-bpy) and 1,1'
      bis(diphenylphosphino)ferrocene (dppf)] to give dinuclear PCP pincers
      [{Pd(PCP)}(2)(micro-L)][OTf](2) (L = 4,4'-bpy, 2; dppf,3). [PdCl(PCP)] also
      reacts with 4-mercaptopyridine in the presence of KOH to give a Lewis basic
      pincer with a free pyridine functional group [Pd(4-Spy)(PCP)]4. Its metalloligand
      character is exemplified by the isolation of an asymmetric dinuclear double
      pincer complex [{Pd(PCP)}(2)(micro-4-Spy)][PF(6)] 6 bridged by an ambidentate
      pyridinethiolato ligand. Complexes 1, 2, 3, 4 and 6 have been characterized by
      single-crystal X-ray diffraction analyses.

PMID- 18060116
TI  - The first 1D twofold interpenetrating metal-organic network generated by 1D
      triple helical chains with nanosized cages.
AB  - Reaction of AgPF(6) with the asymmetric ligand 1,6-dihydro-2-methyl-6-oxo-(3,4'
      bipyridine)-5-carbonitrile (1), afforded a significant silver coordination
      polymer {[Ag(2)(1)(3)](2).(CH(3)OH)(3).(PF(6))(4)}(n) (2) with unique 1D twofold
      interpenetrating metal-organic frameworks constructed by 1D triple helical chains
      with nanosized cages hosting counterions as guests. This compound exhibits high
      thermal stability and blue-shift emission with large intensity enhancement
      compared with that of the free ligand.

PMID- 18060117
TI  - Methylated cyclodextrins: an efficient protective agent in water for zerovalent
      ruthenium nanoparticles and a supramolecular shuttle in alkene and arene
      hydrogenation reactions.
AB  - Zerovalent ruthenium(0) nanoparticles in the size range of 2.5 nm were easily
      prepared by chemical reduction of ruthenium salt with an excess amount of sodium
      borohydride and were efficiently stabilized by methylated cyclodextrins. The
      optimization of the catalytic system has been carried out in terms of stability
      and catalytic activity, considering the hydrogenation of olefinic compounds under
      biphasic liquid-liquid conditions. Efficient and controlled chemoselectivities
      were obtained in the hydrogenation of arene derivatives by the relevant choice of
      cavity and methylation degree of the cyclodextrins. Finally, the hydrogenation of
      alpha- and beta-pinenes leads to the major formation of cis-pinanes, interesting
      synthons for fine chemistry, with high diastereoisomeric excesses.

PMID- 18060118
TI  - Highly selective metal mediated ortho-alkylation of phenol. First platinum
      containing organometallic chromane analogues.
AB  - We were able, for the first time, to synthesize and characterize Pt derivatives
      with a structural shape similar to vitamin E, having a metalla-chromane core. The
      formation reaction mechanism includes an unexpected highly selective ortho
      aromatic electrophilic substitution on phenol, operated by [PtCl(eta(1)
      C(2)H(4)OR)(N-N)], R = Me or Ph, and a final cyclization step. The X-ray
      structure of one of the new metalla-chromane complexes [Pt(EtPh)(phen)],1a, (EtPh
      = 2-(ethan-2'-yl-kC(1))-1-phenolato-k0(1), phen = 1,10-phenanthroline) is
      reported. Cytotoxicity and Pt uptake measurements, performed on HeLa cancer
      cells, show an interesting structure-activity correlation for the new metalla
      chromane analogues 1a and [Pt(MeOEtPh)(phen)], 1b, (MeOEtPh = 2-(ethan-2'-yl
      kC(1))-4-(methoxy)-1-phenolato-k0(1)), being the structurally closest to vitamin
      E and also the most active.

PMID- 18060119
TI  - Two-photon absorption and photoluminescence of europium based emissive probes for
      bioactive systems.
AB  - Observation of two-photon excitation (760 nm) and emission of two responsive
      water soluble europium complexes is reported with cross-sections of up to 2 GM.
      Two-photon excitation spectra have also been measured, acquisition being achieved
      by the use of a cavity-dumped mode locked Ti-sapphire laser. Time-gated detection
      is used to differentiate the ligand fluorescence and metal centred emission in
      these europium complexes.

PMID- 18060120
TI  - Metal mediated synthesis of substituted cyclooctatetraenes.
AB  - Substituted cyclooctatetraenes are a class of interesting and important compounds
      both theoretically and synthetically. Since Reppe first discovered the Ni
      catalyzed tetramerization of ethyne affording cyclooctatetraene in 1948,
      transition metal mediated synthesis of this type of compounds has become a
      primary methodology. In this Feature Article, based on our own recent results and
      other groups' related reports, we describe major achievements on transition metal
      mediated or catalyzed synthetic methods for substituted cyclooctatetraenes, with
      focus on reaction patterns, mechanisms, and structural diversity of products.

PMID- 18060121
TI  - Catalytic hydrogenation of polar organic functionalities based on Ru-mediated
      heterolytic dihydrogen cleavage.
AB  - This article highlights Ru complexes, which effect catalytic hydrogenation of
      polar organic functionalities containing C-O bonds other than aldehydes or
      ketones. The unique ability of Ru complexes to undergo heterolytic dihydrogen
      cleavage seems to play a key role in these catalyses.

PMID- 18060122
TI  - Construction of stereodefined 1,1,2,2-tetrasubstituted cyclopropanes by acid
      catalyzed reaction of aryldiazoacetates and alpha-substituted acroleins.
AB  - Michael-initiated ring closure of aryldiazoacetates and alpha-substituted
      acroleins under acid catalysis offers a unique opportunity for the
      stereoselective formation of various tetrasubstituted cyclopropanes.

PMID- 18060123
TI  - Rapid and controllable covalent functionalization of single-walled carbon
      nanotubes at room temperature.
AB  - We report a rapid and efficient procedure to functionalize SWNT where free
      radicals generated at room temperature by a redox reaction between reduced SWNT
      and diacyl peroxide derivatives were covalently attached to the SWNT wall.

PMID- 18060124
TI  - Chlorodifluoromethyl phenyl sulfone: a novel non-ozone-depleting substance-based
      difluorocarbene reagent for O- and N-difluoromethylations.
AB  - Chlorodifluoromethyl phenyl sulfone, a previously unknown compound that can be
      readily prepared from non-ODS-based precursors, was found to act as a robust
      difluorocarbene reagent for O- and N-difluoromethylations.

PMID- 18060125
TI  - The N-donor stabilised cyclotriphosphazene hexacation [P3N3(DMAP)6]6+.
AB  - The cyclotriphosphazene P(3)N(3)Cl(6) reacts with six equivalents of DMAP (4
      (dimethylamino)pyridine) in superheated chloroform to form crystals of
      composition [P(3)N(3)(DMAP)(6)]Cl(6).19CHCl(3) comprising [P(3)N(3)(DMAP)(6)](6+)
      ions, which host five chloride ions in basket-type cavities on either side of the
      ring and at equatorial positions via tetradentate ortho-H-donor arrangements.

PMID- 18060126
TI  - Enantioselective organocatalytic substitution of alpha-cyanoacetates on imidoyl
      chlorides--synthesis of optically active ketimines.
AB  - The enantioselective substitution of alpha-cyanoacetates on imidoyl chlorides
      under phase-transfer catalytic conditions is presented; a simple quinidine
      derived phase-transfer catalyst gives access to the products, highly substituted
      ketimines, in generally good yields and up to 90% ee.

PMID- 18060127
TI  - Picosecond infrared probing of the vibrational spectra of transients formed upon
      UV excitation of stacked G-tetrad structures.
AB  - The photophysical properties of stacked G-tetrads in diverse systems, including
      concentrated solutions of 5'-guanosine monophosphate (5'-GMP), polyguanylic acid
      (poly(G)) and the G-rich oligodeoxynucleotide sequence characteristic of human
      telomeric DNA, are probed by ps-TRIR and compared to those of the monomeric 5'
      GMP.

PMID- 18060128
TI  - Large spin, magnetically anisotropic, octametallic vanadium(iii) clusters with
      strong ferromagnetic coupling.
AB  - Syntheses, structural and magnetic and EPR data are reported for two octametallic
      V(III) clusters with anisotropic S = 4 ground states arising from strong
      ferromagnetic exchange interactions.

PMID- 18060129
TI  - Determination of the attenuation factor in fluorene-based molecular wires.
AB  - Fluorene-based bridges exhibit a molecular wire-like behaviour in C(60)-wire
      exTTF systems with a very low attenuation factor (beta = 0.09 A(-1)).

PMID- 18060130
TI  - Versatile PEG-derivatized phosphine oxide ligands for water-dispersible metal
      oxide nanocrystals.
AB  - We report the simple synthesis of poly(ethylene glycol)(PEG)-derivatized
      phosphine oxide ligands for water-dispersible metal oxide nanocrystals.

PMID- 18060131
TI  - A photochromic porphyrin-perinaphthothioindigo conjugate and its two-photon
      absorption properties.
AB  - A porphyrin-perinaphthothioindigo conjugate having two-photon absorption cross
      sections of approximately 2000 GM and approximately 700 GM for trans- and cis
      isomers, respectively, was synthesized and exhibited clear photochromic behavior
      upon one-photon and two-photon excitation.

PMID- 18060132
TI  - Reversible switching of substrate activity of poly-N-isopropylacrylamide peptide
      conjugates.
AB  - The activity of smart polymer peptide conjugates towards chymotrypsin catalyzed
      hydrolysis was reversibly switched on and off using temperature as the trigger.

PMID- 18060133
TI  - Single-walled carbon nanotubes binding to human telomeric i-motif DNA:
      significant acceleration of S1 nuclease cleavage rate.
AB  - Single-walled carbon nanotubes (SWNTs) binding to human telomeric i-motif DNA can
      significantly accelerate S1 nuclease cleavage rate by increasing the enzyme
      turnover number.

PMID- 18060135
TI  - Selective gas sorption property of an interdigitated 3-D metal-organic framework
      with 1-D channels.
AB  - An interdigitated 3-D metal-organic framework, [Cd(3)(OH)(2)L(4)(H(2)O)(2)], with
      1-D channels was prepared using 4-aminophenyl-1H-tetrazole (HL) and Cd(II) ions,
      where the host framework shows selective gas sorption behavior that is based on
      the different nature of the interactions between the gas and the framework rather
      than on the size-exclusion effect of the micropores.

PMID- 18060134
TI  - Bowl-shaped Cu(I) metallamacrocyclic ethylene and carbonyl adducts as structural
      analogues of organic calixarenes.
AB  - Three novel Cu(I) metallacalixarenes with C(2)H(4) and CO legs, in which an anion
      is accommodated in the inside cavity, were self-assembled by anion templation and
      have been structurally characterized.

PMID- 18060136
TI  - A series of nickel phosphonate-carboxylate cages.
AB  - Three new polymetallic nickel(II) phosphonate complexes are reported; in one cage
      the twelve nickel centres are arranged at the vertices of a truncated tetrahedron
      in a similar manner to a Keggin ion.

PMID- 18060137
TI  - Unique adsorption properties of organic-inorganic hybrid zeolite IEZ-1 with
      dimethylsilylene moieties.
AB  - The interlayer silylation of pure silica PLS-1 with dichlorodimethylsilane gave a
      novel organic-inorganic hybrid zeolite IEZ-1, of which the micropores are able to
      adsorb benzene molecules, in contrast to its purely inorganic analogue IEZ-2.

PMID- 18060138
TI  - High-connectivity networks: characterization of the first uninodal 9-connected
      net and two topologically novel 7-connected nets.
AB  - Ring and cage aggregates containing the large alkali metals potassium or rubidium
      have proven to be excellent building blocks for the creation of high-connectivity
      nets, as demonstrated by their use as septahedral and nonahedral nodes in
      synthesis of two new types of 7-connected nets and the first ever example of a 9
      connected net.

PMID- 18060139
TI  - Non-covalent interactions of a drug molecule encapsulated in a hybrid silica gel.
AB  - The drug molecule Propranolol has been encapsulated by a sol-gel process in an
      organic-inorganic hybrid matrix by in-situ self-assembly; the 2D HETCOR solid
      state NMR spectroscopy provides direct proof of the intimate spatial relationship
      between the host matrix and guest drug molecules.

PMID- 18060140
TI  - A facile solution-chemistry method for Cu(OH)2 nanoribbon arrays with noticeable
      electrochemical hydrogen storage ability at room temperature.
AB  - Cu(OH)(2) nanoribbon arrays were synthesized by a simple room-temperature
      solution reaction for the first time, which exhibited noticeable hydrogen storage
      capacity and large BET surface area.

PMID- 18060141
TI  - Heat-set gels and egg-like vesicles using two component gel system based on
      chiral calix[4]arenes.
AB  - Chiral calix[4]arenes bearing long tertiary alkyl groups at the upper rim and S-1
      phenylethylamine groups at the lower rim can form heat-set gels and egg-like
      vesicles enantioselectively with d-2,3-dibenzoyltartaric acid in cyclohexane,
      which is the first example of heat-set gels resulting from difference in
      interactions between two component gelators: in addition, the diameter of
      vesicles decreased with the increase in length of alkyl groups, which could be
      used to control the size of the vesicles.

PMID- 18060142
TI  - Supramolecular double helical Cu(I) complexes for asymmetric cyclopropanation.
AB  - Chiral double-stranded helicates, formed between Cu(I) ion and C(2)-symmetric
      oligopyridines, were used for catalytic asymmetric cyclopropanation of alkenes;
      low catalyst loadings (0.2 mol%), high TONs (up to 404) and short reaction times
      (30-60 min) were achieved with [Cu(2)L(2)]OTf(2)(L = chiral C(2)-symmetric
      terpyridine).

PMID- 18060143
TI  - A fluorescent photochromic compound for labeling biomolecules.
AB  - A fluorescent photochromic compound, composed of diarylethene, fluorescein and
      succinimidyl ester units, was developed for the controllable fluorescent labeling
      of biomolecules based on a small molecule.

PMID- 18060144
TI  - Stable photoinduced charge separation in heptacene.
AB  - Heptacene, generated in inert gas matrices by photobisdecarbonylation of a
      bridged alpha-diketone precursor, undergoes ionization into radical anion and
      radical cation upon UV irradiation.

PMID- 18060145
TI  - A novel metal-organic ternary topology constructed from triangular, square and
      tetrahedral molecular building blocks.
AB  - A novel metal-organic network [Cu(4)(5-NH(2)-1,3
      bdc)(4)(pyridine)(2)(H(2)O)(2)](n), displaying an unprecedented topology has been
      constructed utilizing the different coordinating functional groups of 5-NH(2)-1,3
      bdc to generate a ternary network based upon vertex-linked triangular, square and
      tetrahedral molecular building blocks (MBBs).

PMID- 18060146
TI  - Trapped inorganic phosphate dimer.
AB  - Single crystal X-ray crystallographic signature of the pentafluorophenyl
      substituted tripodal urea-based receptor shows formation of a pseudo dimeric cage
      which also encapsulates a phosphate dimer via numerous hydrogen bonding and
      anion[dot dot dot]pi interactions.

PMID- 18060147
TI  - Multivalent polymer vesicles via surface functionalization.
AB  - A new method was developed for the conjugation of multivalent dendritic groups to
      polymer vesicle surfaces.

PMID- 18060148
TI  - SERS opens a new way in aptasensor for protein recognition with high sensitivity
      and selectivity.
AB  - SERS aptasensors for protein recognition based on Au nanoparticles labeled with
      aptamers and Raman reporters have been developed, which opens a new way for
      protein recognition of high sensitivity and selectivity.

PMID- 18060149
TI  - An unprecedented co-crystal including a cis-high-spin and a trans-low-spin FeII
      complex molecule.
AB  - Two structurally and magnetically nonequivalent isomeric molecules, a cis-high
      spin and a trans-low-spin isomer constitute the unit cell of a new iron(II)
      complex {cis-[FeL(B5)(NCS)(2)].trans-[FeL(B5)(NCS)(2)]}.CH(3)OH, , (L(B5) = N,N'
      bis((2-N-methylimidazol-1-yl)methylene))-2,2-dimethylpropane-1,3-diamine); the
      synthesis, X-ray structure, and magnetic and Mossbauer study of this unique
      example of co-crystallised geometric, conformational and electronic isomers are
      reported.

PMID- 18060150
TI  - A new family of ionic liquids based on N,N-dialkyl-3-azabicyclo[3.2.2]nonanium
      cations: organic plastic crystal behaviour and highly reversible lithium metal
      electrodeposition.
AB  - A new family of ionic liquids based on N,N-dialkyl-3-azabicyclo[3.2.2]nonanium
      cations exhibits wide electrochemical windows, excellent lithium deposition
      stripping behaviour and plastic crystal properties and therefore these cation
      structures, which are extensions from pyrrolidinium- and piperidinium-based
      cations, complement a set of related structures for a systematic study on the
      physicochemical properties of ionic liquids.

PMID- 18060151
TI  - A Lewis-basic, dionio-substituted phosphane.
AB  - Bis{guanidine} H(2)C{hpp}(2)[hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2
      a]pyrimidine] reacts with PPhCl(2) to generate the dionio-substituted phosphane,
      [H(2)C{hpp}(2)PPh](2+)[Cl](-)(2) which, despite the formally dicationic
      phosphorus centre, forms an unprecedented coordination compound with platinum.

PMID- 18060152
TI  - Total syntheses of (+)-7-epi-goniofufurone, (+)-goniopypyrone and (+)
      goniofufurone from a common precursor.
AB  - Total syntheses of (+)-7-epi-goniofufurone, (+)-goniopypyrone and (+)
      goniofufurone have been achieved from an advanced common precursor formed from D
      (+)-mannitol by changing the carbinol protection profile.

PMID- 18060153
TI  - Manganese and iron flavonolates as flavonol 2,4-dioxygenase mimics.
AB  - Mononuclear manganese(II) and iron(III) flavonolates were synthesized as
      synthetic enzyme-substrate complexes, and their oxygenation reactions as
      biomimetic functional models with relevance to flavonol 2,4-dioxygenases are
      briefly described.

PMID- 18060154
TI  - Palladium nanoparticles captured onto spherical silica particles using a urea
      cross-linked imidazolium molecular band.
AB  - Palladium nanoparticles were captured onto spherical silica particles using a
      molecular band composed of imidazolium chloride and urea moieties to form
      raspberry-like Pd@SiO2 composites, which can be recovered and reused without any
      loss of catalytic activity in Suzuki-Miyaura coupling.

PMID- 18060155
TI  - Isolation and structural elucidation of a key aluminoaromatic intermediate and
      evidence for dismutation phenomena in TMP-alumination chemistry.
AB  - Lithium TMP-aluminate "(i)Bu(3)Al(TMP)Li" undergoes dismutation in THF solution
      to precipitate the tetraalkylaluminate [{Li.(THF)(4)}(+){Al((i)Bu)(4)}(-)], but
      reacts kinetically as a TMP base towards N,N-diisopropylbenzamide to afford the
      crystalline ortho-aluminated species
      [(THF)(3).Li{O([=C)N((i)Pr)(2)(C(6)H(4))}Al((i)Bu)(3)] and TMPH.

PMID- 18060156
TI  - Decarboxylative reduction of free aliphatic carboxylic acids by photogenerated
      cation radical.
AB  - The decarboxylation of free carboxylic acids was effected by a photogenerated
      cation radical of phenanthrene to yield the reduction product in the presence of
      a thiol, which provides an alternative method to the Barton decarboxylation
      procedure for aliphatic acids such as N-Boc amino acids.

PMID- 18060157
TI  - Colloidal particles at liquid interfaces.

PMID- 18060158
TI  - Fabrication of magnetically-functionalized lens- and donut-shaped microparticles
      by a surface-formation technique.
AB  - We report a simple method for the preparation of magnetically-functionalized lens
      like and donut-shaped polymeric microparticles, based on spreading a magnetite
      doped paraffin-polymer solution at the air/water interface in the presence of an
      external magnetic field. We examine the parameters that affect the particle
      morphology and interfacial aggregation behaviour.

PMID- 18060159
TI  - Interstitial fractionalization and spherical crystallography.
AB  - Finding the ground states of identical particles packed on spheres has relevance
      for stabilizing emulsions and has a venerable history in the literature of
      theoretical physics and mathematics. Theory and experiment have confirmed that
      defects such as disclinations and dislocations are an intrinsic part of the
      ground state. Here we discuss the remarkable behavior of vacancies and
      interstitials in spherical crystals. The strain fields of isolated disclinations
      forced in by the spherical topology literally rip interstitials and vacancies
      apart, typically into dislocation fragments that combine with the disclinations
      to create small grain-boundary scars. The fractionalization is often into three
      charge-neutral dislocations, although dislocation pairs can be created as well.
      We use a powerful, freely-available computer program to explore interstitial
      fractionalization in some detail, for a variety of power-law pair potentials. We
      investigate the dependence on initial conditions and the final state energies,
      and compare the position dependence of interstitial energies with the predictions
      of continuum elastic theory on the sphere. The theory predicts that, before
      fragmentation, interstitials are repelled and vacancies are attracted from 5-fold
      disclinations. We also use vacancies and interstitials to study low-energy states
      in the vicinity of "magic numbers" that accommodate regular icosadeltahedral
      tessellations.

PMID- 18060160
TI  - Stepwise interfacial self-assembly of nanoparticles via specific DNA pairing.
AB  - In the present work, we succeeded in alternatively depositing inorganic
      nanoparticles and functionalized DNA bases onto the water/oil interface from the
      water and oil bulk phases. The ligands used were functional thymines and
      adenines. Their thiol and phosphate groups were used to cap inorganic
      nanoparticles and their thymine and adenine groups to alter the surface
      functionality of the nanoparticles, thus enabling a layer-by-layer growth fashion
      of nanoparticles at the interface. The multiple particle ligation rendered the
      resulting nanoparticle films rather mechanically robust. As results, the
      freestanding asymmetric bilayer and trilayer films, composed of negatively
      charged Au, positively-charged CdTe, and/or organic Ag nanoparticles were
      constructed; their areas were as large as over several centimetres, depending on
      the sizes of the containers used. Our work should bring up a novel methodology to
      generate asymmetric multilayer films of nanoparticles with a defined control of
      electron or charge across the films.

PMID- 18060161
TI  - Size-selective photocatalytic reactions by titanium(IV) oxide coated with a
      hollow silica shell in aqueous solutions.
AB  - A novel core-shell composite photocatalyst, commercially available titanium(IV)
      oxide (TiO(2)) particles directly incorporated into a hollow amorphous silica
      shell, was fabricated by successive coating of TiO(2) with a carbon layer and a
      silica layer followed by heat treatment to remove the carbon layer. The composite
      induced efficient photocatalytic reactions when relatively small substrates were
      used, such as methanol dehydration and decomposition of acetic acid, without any
      reduction in the intrinsic activity of original TiO(2), but did not exhibit
      efficient photocatalytic activity for decomposition of large substrates,
      methylene blue and polyvinyl alcohol. The unique size-selective properties of the
      composites are due to their structural characteristics, i.e., the presence of a
      pore system and a void space in the silica shell and between the shell and medial
      TiO(2) particles, respectively. The loading of alkylsilyl groups on the surface
      of the composite led to highly photostable floatability: the floated sample also
      induced efficient photocatalytic reaction for decomposition of acetic acid while
      retaining floatation at the gas/water interface.

PMID- 18060162
TI  - Kinetics of CO2 nanobubble formation at the solid/water interface.
AB  - The kinetics of adsorption of CO(2) molecules dissolved in aqueous solution onto
      a hydrophobised silica surface were investigated using a quartz crystal
      microbalance (QCM). The results of this investigation were compared with those
      obtained earlier from tapping mode atomic force microscopy (TMAFM) under the same
      experimental conditions (J. Yang, J. Duan, D. Fornasiero, J. Ralston, J. Phys.
      Chem. B., 2003, 107(25), 6139-6147; ref. 1). The QCM results represent the early
      stage of CO(2) gas adsorption (<20 min), before CO(2) gas bubbles adsorbed on the
      surface can be directly observed by TMAFM. The QCM results confirmed our
      observation from TMAFM imaging: that CO(2) gas molecules present in solution only
      adsorb on silica when its surface is hydrophobic. More importantly, the results
      showed that gas adsorption/bubble growth undergoes two consecutive kinetic
      processes: a slow and a fast adsorption process.

PMID- 18060163
TI  - Water-in-carbon dioxide emulsions stabilized with hydrophobic silica particles.
AB  - W/C emulsions were stabilized using hydrophobic silica particles adsorbed at the
      interface, resulting in average droplet diameters as low as 7.5 microm. A porous
      cross-linked shell was formed about a hydrophilic (colloidal and fumed) silica
      core with a trifunctional silylating agent, (heptadecafluoro-1,1,2,2
      tetrahydrodecyl)triethyoxysilane, to render the particles CO(2)-philic. The
      stability of emulsions comprising equal weights of CO(2) and water was assessed
      with visual observations of settling fronts and the degree of emulsion
      coalescence, and the average drop size was measured by optical microscopy. The
      effect of CO(2) density on both emulsion stability and droplet size was
      determined quantitatively. The major destabilizing mechanism of the emulsions was
      settling, whereas Ostwald ripening and coalescence were not visible at any
      density, even over 7 days. Flocculation of the settling droplets did not occur,
      although gelation of the emulsions through particle interactions resulted after
      longer periods of time. CO(2)-philic particles offer a new route to highly stable
      W/C emulsions, with particle energies of attachment on the order of 10(6)kT, even
      at CO(2) densities as low as 0.78 g ml(-1). At these low densities, surfactants
      rarely stabilize emulsions as the result of poor surfactant tail solvation.

PMID- 18060164
TI  - Determining the mechanical response of particle-laden fluid interfaces using
      surface pressure isotherms and bulk pressure measurements of droplets.
AB  - The mechanical response of particle-laden fluid interfaces is determined by
      measuring the internal pressures of particle-coated drops as a function of the
      drop volume. The particle monolayers undergoing compression-expansion cycles
      exhibit three distinct states: fluid state, jammed state, and buckled state. The
      P-V curves are compared to the surface pressure isotherms Pi-A that are measured
      using a Langmuir trough and a Wilhelmy plate on a flat water-decane interface
      covered with the same particles. We find that in the fluid and jammed states, the
      water drop in decane can be described by the Young-Laplace equation. Therefore in
      these relatively low compression states, the bulk pressure measurements can be
      used to deduce the interfacial tension of the droplets and yield similar surface
      pressure isotherms to the ones measured with the Wilhelmy plate. In the buckled
      state, the internal pressure of the drop yields a zero value, which is consistent
      with the zero interfacial tension measured with the Wilhelmy plate. Moreover we
      find that the compressibility in the jammed state does not depend on the particle
      size.

PMID- 18060165
TI  - On the kinetics of nanoparticle self-assembly at liquid/liquid interfaces.
AB  - We investigate the concentration and size dependent self-assembly of cadmium
      selenide nanoparticles at an oil/water interface. Using a pendant drop
      tensiometer, we monitor the assembly kinetics and evaluate the effective
      diffusion coefficients following changes in the interfacial tension for the early
      and late stages of nanoparticle adsorption. Comparison with the coefficients for
      free diffusion reveals the energy barrier for particle segregation to the
      interface. The formation of a nanoparticle monolayer at the oil/water interface
      is characterised by transmission electron microscopy.

PMID- 18060166
TI  - Contact angle determination of nanoparticles: film balance and scanning angle
      reflectometry studies.
AB  - Stober silica nanoparticles of diameter about 45, 60 and 100 nm and different
      hydrophobicity are used to produce monolayers at a water-air interface. Both the
      surface pressure-area isotherms and the reflectivity angle of incidence curves of
      the layers have been measured in a Wilhelmy film balance. The contact angle of
      the as-prepared particles have been determined from the isotherms by two
      different evaluation methods, and compared to those obtained from in situ
      scanning angle reflectometry (SAR) measurements. SAR is proved to be an effective
      tool for the estimation of contact angles on nanoparticles of different
      wettability, using a modified version of the previously published gradient layer
      model (E. Hild, T. Sesztak, D. Volgyes and Z. Horvolgyi, Prog. Colloid Polym.
      Sci., 2004, 125, 61, ref. 1) for evaluation. The results are in fairly good
      agreement with those determined from the non-dissipative part of the isotherms of
      the as prepared particles, assuming a weakly cohesive film model (S. Bordacs, A.
      Agod and Z. Horvolgyi, Langmuir, 2006, 22, 6944, ref. 2). It seems that the
      traditional way to calculate the contact angle from the film balance experiments
      (J.H. Clint and N. Quirke, Colloids Surf., A, 1993, 78, 277, ref. 3) results in
      unreasonably high contact angles for the investigated systems and the homogeneous
      layer optical model gives unrealistic film thickness values in the case of
      hydrophobic particles.

PMID- 18060167
TI  - Effect of electric-field-induced capillary attraction on the motion of particles
      at an oil-water interface.
AB  - Here, we investigate experimentally and theoretically the motion of spherical
      glass particles of radii 240-310 microm attached to a tetradecane-water
      interface. Pairs of particles, which are moving toward each other under the
      action of lateral capillary force, are observed by optical microscopy. The
      purpose is to check whether the particle electric charges influence the particle
      motion, and whether an electric-field-induced capillary attraction could be
      detected. The particles have been hydrophobized by using two different
      procedures, which allow one to prepare charged and uncharged particles. To
      quantify the hydrodynamic viscous effects, we developed a semiempirical
      quantitative approach, whose validity was verified by control experiments with
      uncharged particles. An appropriate trajectory function was defined, which should
      increase linearly with time if the particle motion is driven solely by the
      gravity-induced capillary force. The analysis of the experimental results
      evidences for the existence of an additional attraction between two like-charged
      particles at the oil-water interface. This attraction exceeds the direct
      electrostatic repulsion between the two particles and leads to a noticeable
      acceleration of their motion.

PMID- 18060168
TI  - Langmuir-Blodgett films of micron-sized organic and inorganic colloids.
AB  - Multilayered films starting with silica or polymer particles in the micron-size
      range have been prepared using the Langmuir-Blodgett technique. The polymer
      particles made of highly cross-linked cores and hydrophilic shells were
      elaborated through a precipitation polymerization method that allows formation of
      particles with a low polydispersity. The influence of the surface function, the
      differences between organic and inorganic systems, and the characterization of
      these materials by means of reflectance infrared spectroscopy are also discussed.

PMID- 18060169
TI  - Contact angles in relation to emulsions stabilised solely by silica nanoparticles
      including systems containing room temperature ionic liquids.
AB  - We report measured and calculated oil-ionic liquid, water-ionic liquid and oil
      water contact angles on silica surfaces which have been hydrophobised to
      different extents by silanisation. Based on the idea that the contact angle
      formed by a liquid-liquid interface with a particle adsorbed at that interface is
      a key determinant of the strength of particle adsorption and the tendency of the
      adsorbed particle film to curve, we correlate the contact angle data with the
      phase inversion points and stabilities of the corresponding particle-stabilised
      emulsions.

PMID- 18060170
TI  - Effect of electrolyte in silicone oil-in-water emulsions stabilised by fumed
      silica particles.
AB  - Partially hydrophobised fumed silica particles are used to make silicone oil-in
      water emulsions at natural pH of the aqueous phase. The stability and rheological
      properties of the emulsions and suspensions are studied at NaCl concentrations in
      the range 0-100 mM. It is found that all emulsions are very stable to coalescence
      irrespective of the NaCl concentration. However, a strong effect of electrolyte
      on the creaming and rheological properties is observed and linked to the particle
      interactions in aqueous suspensions. The creaming rate and extent are large at
      low electrolyte concentrations but both abruptly decrease at salt concentrations
      exceeding the critical flocculation concentration of the suspension
      (approximately 1 mM NaCl). The drastic improvement of the stability to creaming
      is attributed to the formation of a visco-elastic three-dimensional network of
      interconnected particles and emulsion droplets.

PMID- 18060171
TI  - Ion partitioning at the oil-water interface as a source of tunable electrostatic
      effects in emulsions with colloids.
AB  - We present a combined experimental and theoretical investigation of the
      surprisingly strong electrostatic effects that can occur in mixtures of low- and
      high-polar liquids (e.g. oil-water emulsions), here in the presence of colloidal
      particles. For our experiments, we used confocal microscopy imaging, supplemented
      with electrophoresis and conductivity measurements. Theoretically, we studied our
      systems by means of a modified Poisson-Boltzmann theory, which takes into account
      image charge effects and the electrostatic self-energies of the micro-ions in the
      different dielectric media. Our results show that the unequal partitioning of
      micro-ions between the two liquid phases is the common driving force behind most
      of the observed electrostatic effects. The structural signatures of these effects
      typically develop on a time scale of hours to days and are qualitatively well
      described by our theory. We demonstrate how the partitioning process and its
      associated phenomena can be controlled by shifting the balance of the interlocked
      ionic dissociation and partitioning equilibria. Moreover, we present strong
      experimental proof that the two-dimensional colloidal crystals at the oil-water
      interface are due to long-ranged Coulombic repulsion through the oil phase. The
      acquired insight in the role of electrostatics in oil-water emulsions is
      important for understanding the interactions in particle-stabilized ('Pickering')
      and charge-stabilized emulsions, emulsion production, encapsulation and self
      assembly.

PMID- 18060172
TI  - Study on aluminium-based single films.
AB  - In the present paper the authors studied isolated metallic films made from the
      same material used for making metallic foams, and then characterised their
      properties. Metal films were made from a liquid aluminium alloy reinforced with
      ceramic particles of known concentration. Melts without such particles were also
      investigated. It is shown that stable films could not be made from Al-Si alloy
      having no particles, and just extremely thin and fragile films could be made from
      commercially-pure Al. In contrast, aluminium alloys containing particles such as
      SiC and TiB(2) allowed pulling thin, stable films, which did not rupture.
      Significant thinning of films was observed when the particle concentration in the
      melt decreased. By in situ X-ray monitoring of liquid films during pulling, film
      thickness and drainage effects within the liquid film could be studied. The
      morphology and microstructure of films was characterised after solidification.
      Our work shows that the question of how foams are stabilised can be studied using
      a simplified system such as a film, instead of having to deal with the multitude
      of different structural elements present in a foam.

PMID- 18060173
TI  - Synergistic effect of silica nanoparticles and charged surfactants in the
      formation and stability of submicron oil-in-water emulsions.
AB  - The influence of hydrophilic silica nanoparticles on the emulsification of a
      triglyceride oil (Miglyol812) in the presence of charged surfactants (lecithin or
      oleylamine) and the long term stability of the resultant oil-in-water emulsions
      are reported. A synergistic effect of nanoparticles and surfactants in improving
      emulsification and stability to coalescence is evident only when the silica
      nanoparticles are initially added to the oil phase. When nanoparticles are
      included from the water phase, no synergistic stabilisation was observed due to
      electrostatic bridging or unfavourable attachment due to the repulsive
      electrostatic and hydration forces. Free energies of adsorption for silica
      nanoparticles at the oil-water interface calculated from experimentally
      determined interfacial tensions and three phase contact angles can be correlated
      to long-term emulsion stability only when silica is added from oil phase.

PMID- 18060174
TI  - Guiding the location of nanoparticles into vesicular structures: a morphological
      study.
AB  - The present paper investigates the selective incorporation of preformed
      nanoparticles (hydrophobic Au-NP (2 nm); hydrophilic Au-NP (12 nm); hydrophobic
      CdSe-NP (1.9 nm); retrovirus-particles (approximately 30 nm)) into the interface
      of lipid vesicles and polymersomes via TEM and DLS investigations. Lipid
      membranes were made from N,N-dimethyl-N,N-dioctadecylammonium bromide (DODAB), di
      oleoyl-phosphatidylcholine (DOPC), whereas polymersome-membranes were fabricated
      from the diblock copolymer poly-(butadiene-block-ethylenoxide). Stabilization of
      the final structures was achieved via sol/gel processes at the outside of the
      membranes, thus stabilizing the structure by a silicate shell. Whereas
      hydrophobic Au-NPs can be successfully embedded into the polymersome- and lipid
      vesicle membranes, hydrophilic nanoparticles were found evenly distributed in the
      inner- and outer compartments of the vesicles and polymersomes. Significant
      effects such as size reduction, selective enrichment of all nanoparticles within
      only few polymersomes as well as budding effects of larger entities (i.e., viral
      particles) are described.

PMID- 18060175
TI  - Permeability of silk microcapsules made by the interfacial adsorption of protein.
AB  - The assembly of colloidal particles at a liquid/liquid interface is a useful
      technique for the formation of a large variety of structures. Recently, we
      created a new method which uses liquid/liquid interfaces to assemble recombinant
      silk proteins into thin-shelled microcapsules. These microcapsules are
      mechanically stable and well suited to applications such as enzyme therapy and
      artificial cells. In this paper the permeability properties of these
      microcapsules are investigated using a novel measurement technique. It is found
      that the microcapsules are polydisperse in their permeabilities, but for all
      measured microcapsules the permeability is in the range required to protect
      encapsulants from immunoglobulin proteins, while allowing small molecules to
      enter the capsule freely.

PMID- 18060176
TI  - Contact angle determination of micro- and nanoparticles at fluid/fluid
      interfaces: the excluded area concept.
AB  - A novel and simple method for the determination of the contact angle of nano- and
      microparticles at the liquid/air interface is proposed. The principle is based on
      the consideration of differences between the pressure/area isotherms of a 2D
      single-component system of a surfactant and those of binary systems comprised of
      the same surfactant and the particles to be studied. The theoretical analysis of
      the contact-angle behavior in this system upon compression allows the prediction
      of direction of the particles' squeezing out of the surface layer and therefore
      the distinction between the particles with high contact angle (Theta(p) > 90
      degrees) and low (Theta(p) < 90 degrees) hydrophobicity. The application of this
      method to microparticles of two different hydrophobicities demonstrates good
      agreement between the obtained contact angles and the corresponding degrees of
      hydrophobicity given by the particle provider.

PMID- 18060177
TI  - Pickering emulsions with stimulable particles: from highly- to weakly-covered
      interfaces.
AB  - We study oil-in-water emulsions stabilised by pH-sensitive colloidal silica or
      latex particles. Depending on the composition of the continuous phase, the same
      type of particles and the same emulsification process lead to emulsions
      characterised either by large drops densely covered by the particles, or to small
      droplets which are weakly covered. The two kinetically stable states can be tuned
      reversibly by using pH or salinity as compositional stimuli. We examine the
      emulsions' behaviour in these two limiting cases and we discuss the possible
      mechanisms allowing stabilisation, especially in the case of low surface
      coverage.

PMID- 18060178
TI  - Interfacial rheology of stable and weakly aggregated two-dimensional suspensions.
AB  - The interfacial rheological properties of stable and weakly aggregated two
      dimensional suspensions are studied experimentally using a magnetic rod
      interfacial rheometer. Particle monolayers with well controlled structures were
      prepared. Charged polystyrene particles create two-dimensional colloidal crystals
      at the water-decane interface over a wide range of concentrations. Under similar
      conditions a predominantly liquid structure is obtained at the water-air
      interface for the same particles. The addition of appropriate combinations of the
      anionic surfactant sodiumdodecylsulfate (SDS) and sodium chloride (NaCl) to the
      aqueous subphase leads to a destabilization of these monolayers with the
      formation of fractal aggregates at low concentrations and a heterogeneous gel
      forming as the surface coverage is increased. After the structures have been
      built up a reproducible structure can be obtained, of which the interfacial
      rheological properties can be investigated using a magnetic rod stress rheometer.
      In all cases, numerical calculations were used to assess the importance of
      instrumental artifacts and the effect of the coupling between surface and
      subphase flows. The rheology of aggregated suspensions was compared to the
      reference case of a colloidal crystal. The two-dimensional aggregated suspensions
      display rheological features which are similar to their three-dimensional
      counterparts. These include an elastic response with small linearity limits, a
      power law dependence on surface coverage and a dependence on the strength of
      attraction. The results shed some light on the possible role of interfacial
      rheology on the stability of particle laden high interface systems. Additionally,
      the 2D suspensions could present fundamental insights in the rheological
      properties of dense colloidal suspensions.

PMID- 18060179
TI  - The effect of double-chain surfactants on armored bubbles: a surfactant
      controlled route to colloidosomes.
AB  - We find that the gas phases of air bubbles covered with anionic or cationic
      polystyrene latex particles dissolve on exposure to cationic and catanionic
      surfactants. The particles on the bubble interface are released as singlets or
      aggregates when the surfactant has a single hydrophobic chain, while porous
      colloidal capsules (colloidosomes) with the same aqueous phase inside as out are
      obtained when the surfactant has two hydrophobic chains. The formation of
      colloidosomes from the particle-covered bubbles does not appear to depend
      significantly on the charge of the particles, which makes it unlikely that
      bilayers of surfactant are stabilizing the colloidosome. While the exact
      mechanism of formation remains an open question, our method is a simple one-step
      process for obtaining colloidosomes from particle-covered bubbles.

PMID- 18060180
TI  - Population distance between Dakshina Kannada (South India) and Gujarati (North
      India) population using infracranial nonmetric traits.
AB  - Infracranial nonmetric variations have been considered for determining population
      distance between different regions and continents, in recent times. We studied
      different infracranial nonmetric traits from the Dakshina Kannada (South India)
      region to compare with the data available from the Gujarati (North India) region.
      The mean measure of divergence between the two different geographic regions
      showed significant variation. In our study, the incidence like i) Allen's fossa
      of the femur, ii) plaque formation in the upper end of the femur, iii) exostosis
      in trochanteric fosse of femur, iv) third trochanter of femur, v) os trigonum of
      talus, vi) medial talar facet, vii) peroneal tubercle of calcaneus, viii)
      bipartite transverse foramen in the cervical vertebra, too showed significant
      side difference.

PMID- 18060181
TI  - Biology of metalloproteinases.
AB  - Matrix metalloproteinases (MMPs) occupy a central role in embryogenesis and in
      normal physiological conditions, such as proliferation, cell motility,
      remodeling, wound healing, angiogenesis, and key reproductive events. MMPs form a
      multigenic family of proteolytic, zinc-dependent enzymes, with 26 members
      described until present, displaying multidomain structures and substrate
      specificities. MMPs are involved in both the turnover and degradation of
      extracellular matrix (ECM) proteins and in the processing, activation, or
      deactivation of a variety of soluble factors. They are regulated at the level of
      transcription, activation of the precursor zymogens, and inhibition mainly by
      tissue inhibitors of metalloproteinases (TIMPs). Any loss in activity control may
      result in various diseases. This review provides an update of biological
      functions of MMPs, facilitating the understanding of the complex pathogenic
      mechanisms of medical conditions characterized by imbalance between MMP and TIMP
      expression. The design of potent specific inhibitors for MMPs represents a
      scientific challenge for the development of new therapies.

PMID- 18060182
TI  - Hyperplasia, metaplasia, dysplasia and neoplasia lesions in chronic cholecystitis
      - a morphologic study.
AB  - The aim of the study was to analyze the association between chronic
      cholecystitis, premalignant lesions and gallbladder cancer. The group consisted
      in 3901 cases of cholecystectomies, diagnosed as acute cholecystitis (250 cases -
      6.4%), chronic cholecystitis (3619 cases - 92.8%) and gallbladder carcinoma (32
      cases - 0.8%). Chronic cholecystitis associated premalignant lesions as follows:
      hyperplasia in 124 cases (7.8%), metaplasia in 86 cases (5%) and dysplasia in 10
      cases (0.4%). Only in nine cases, the diagnosis of gallbladder carcinoma was
      formulated presumptively, before surgery; for the other 23 cases this diagnosis
      was established after the pathologic exam on the cholecystectomy piece. In the
      areas adjacent to the neoplastic proliferation, premalignant lesions
      (hyperplasia, metaplasia, dysplasia) were identified in 34.4% cases. The
      identification of premalignant modifications in the morphologic background of
      chronic cholecystitis is an argument in favor of the metaplasia-dysplasia
      neoplasia sequence and justifies recent recommendations for the performing of
      colecystectomy.

PMID- 18060183
TI  - Apoptosis in cutaneous melanomas.
AB  - Cutaneous melanomas has become one of the most discussed and studied tumor
      because its particular immunologic development but also its increasing rate
      worldwide in the last decades. Even thought many patients are diagnosed at an
      early stage, the death rate continues to rise due to the increasing incidence of
      more advanced lesions. The aim of this study is to detect apoptosis in 30 cases
      of cutaneous melanomas using the in situ end-labeling technique (TUNEL) who
      quantify apoptotic cell death at single cell level and tissues.

PMID- 18060184
TI  - The aspects of angiogenesis in anal canal carcinomas compared with that in
      colorectal carcinomas.
AB  - AIM: To compare the angiogenesis in anal canal carcinomas (ACC) with that in
      colorectal carcinomas (CRC). METHODS: A number of 507 CRC, surgical specimens,
      were analyzed, 12 cases (1.97%) being ACC. In 20 cases from left and right colon
      (CRC) and in the 12 ACC we analyzed the immunohistochemical parameters related to
      angiogenesis, utilizing the following LabVision antibodies: CD31, CD105
      (endoglin) and VEGF1. Morphometrical analysis and positive cell counting were
      performed in the tumoral and peritumoral tissue. Immunoperoxidase method was
      used. RESULTS: The average age was 63.17 +/- 10.87 years in CRC, respectively
      57.9 +/- 10.05 years in the ACC (p<0.0001). Compared with CRC the ACC occur more
      frequently at the females (58%). Angiogenesis was expressed in the majority of
      cases. In CRC, the microvascular density (MVD) was higher than that from ACC. The
      ratio CD31/CD105 was 1 in ACC and 3 in CRC. VEGF was positive in 25% of ACC and
      80% of CRC. In CRC were more mature vessels, marked only with CD31 than immature
      vessels or endothelial isolated cells marked with both CD31 and CD105. In ACC
      prevailed the neoformed vessels marked with both CD31 and CD105. CONCLUSIONS: The
      performed assessments have showed a higher incidence of ACC at females and at
      younger ages. The angiogenesis in ACC was not so high like in CRC and the
      immature neoformed vessels was more frequently. In ACC, the antiangiogenic
      treatment that regards the VEGF inhibition seems to be not as efficient as in
      CRC. The radiotherapy could stop the angiogenesis and could inhibit the vessels'
      maturation.

PMID- 18060185
TI  - The venous system of the lower limbs.
AB  - The venous system anatomy of the lower limbs and especially its functionality
      still presents half-lighted areas, fact easily qualified as incredible for the
      third millennium. Our dissections on fresh amputation segments, methylene blue
      injected in superficial veins or in deeper veins pointed out that venous
      circulation is much more complex than it seemed, that there are subdermal
      collectors connected to the saphene trunks which permit bidirectional transfer of
      blood mass to saphene venous roots or to derm. The dermal plexus has also a
      complex connection with the deep venous system by Delater perforators, by
      perforators, which drain saphene systems after having previously received dermal
      affluents, and by Delater equivalences (submillimetric perforators) that provide
      blood mass transfer from deep to surface under the conditions of a moderate and
      temporary venous hypertension. High- and long-term venous hypertension determines
      the valvular device deterioration of classical perforators making possible a
      pathological bi-directional flow.

PMID- 18060186
TI  - Morphologic and histochemical changes in the skin of patients with scleroderma.
AB  - BACKGROUND: Systemic sclerosis or scleroderma is a rare collagen disease,
      characterized by insufficient angiogenesis. Few data are available about the
      morphologic and histochemical peculiarities of the skin in these patients with
      this condition. The purpose of the present work was to evaluate the histochemical
      aspects of sclerodermic skin, obtained through biopsy of the typical lesions from
      the forearm skin. PATIENTS AND METHODS: The study was conducted on 31 patients,
      from which skin biopsies were obtained, after informed consent. The specimens
      were fixed in buffer formalin, embedded in paraffin and processed for staining
      with HE, Masson, orcein, Gordon-Sweet silver staining, and alcian blue-safranin,
      in order to identify elastic fibers, reticular fibers, glycosaminoglycans and
      mast cells. Results are partially similar to other studies: the constant
      depletion of elastic fibers in the papillary dermis and disorders of the network
      in the reticular dermis, such as their absence in the skin blood vessels walls.
      The reticular fibers were absent in the papillary dermis, the reaction in the
      reticular dermis structure was variable from a case to another. The staining with
      Alcian blue-Safranin proved that there is a gathering of glycosaminoglycans in
      the superficial papillary dermis, the heterogeneity of collagen fibers and the
      decrease of mast cells in the dermis.

PMID- 18060187
TI  - The endoscopic and morphological forms of early gastric cancer.
AB  - The early gastric cancer is an endoscopic notion in which gastric cancer is
      strictly placed to mucosis and submucosis without extensive manifestations. It is
      the form with favorable prognosis and better survival at 5 and 10 years. Our
      study tries to systematize the debut forms of early gastric cancer and their
      association with the lesions with malignisation risk. We also try to evaluate the
      incidence of endoscopic and histopathologic forms of early gastric cancer found
      in an internal medicine division. Our study included 435 patients with gastric
      cancer endoscopic and histologic diagnosed. Statistically, 64.36% were men and
      35.64% were women, the mean age 48 +/- 7 years. The endoscopic forms of early
      gastric cancer were type I: protruded in 19 cases, type II: superficially in
      eight cases, type III: excavated in six cases. Early gastric cancer is diagnosed
      with difficulty, it represents in 7.58% of the gastric cancer, being most
      frequently asymptomatic. The endoscopic forms frequently found in early gastric
      cancer in the population were type I: protruded and type IIa: superficially
      elevated. The histopathological examination is compulsory at this form of gastric
      cancer, while in advanced gastric cancer endoscopy is often sufficient for
      diagnosis. Analysing the histopathological results of cases diagnosed with early
      gastric cancer we found: 22 cases with intestinal type and 11 cases diffuse type.
      Microscopically, 15 were intramucosal and 18 had submucosal invasion. I and IIa
      lesions were predominantly located at the antrum and are histologically
      differentiated adenocarcinoma. Differentiated carcinoma frequently produces an
      elevated lesion and the border is well demarcated. There are frequent
      opportunities to detect gastric cancer in the early phase and the patient can
      expect a complete cure by the surgical operation or endoscopical mucosal
      resection.

PMID- 18060188
TI  - Morphological study of congenital megaureter.
AB  - Congenital anomalies of the kidney and urinary tract are frequent. They can be
      detected once every 500 ultrasonography fetal examinations. Causes that determine
      a dilated ureter compared to the rest of the urinary tract are still partly
      unknown. If concerning the exploration and the clinical diagnosis of these
      anomalies important progresses have been made, the morphological research is
      still able to bring forth data that, together with genetic researches, may help
      reveal the pathogeny of the disease and may ease the planning of the screening
      genetic tests for early diagnosis. Material and methods. During the surgical
      operations realized in order to recalibrate the ureter, ureter fragments have
      been harvested, colored with 1% tionin, in sections thinner then 1 micron and
      examinated through immersion, ob. 100x. Other fragments have been prepared and
      examinated through electronic microscope. We have followed the structural
      modifications of the muscular tissue, nervous tissue, connective tissue and the
      rapports between these components. Results. Congenital megaureter presents
      qualitative and quantitative anomalies of the connective tissue and muscular
      tissue, and also structural modifications of the nervous tissue. Connective
      tissue. We have noticed the abundance of the connective tissue in congenital
      megaureter. Connective tissue, with an important representation of typical
      elements, such as fibroblasts, mastocytes and plasmocytes is partly hyalinated,
      dissociating muscular fiber bundles and nervous fiber bundles. Connective
      tissue/muscular tissue report is evidently increased. Muscular tissue. Muscular
      fibers are hypoplasic, smooth endoplasmic reticulum is present in the tubular
      form, rare mitochondria are vacuolized. Dense corps are increased in number,
      plasmatic membranes are folded. Sarcoplasm contains vacuolized organites. The
      nuclei are rigged with visible nucleoli. Nervous structures. We have noticed
      varied alterations of the axons and myelin. In some axons there are multiple
      cavities that may produce the opacifiation of the entire axonal structure. The
      proliferation of the myelin sheath under the nodular form or vortex form produces
      the destruction of the axonal structure. Mitochondria are condensed, partially
      vacuolized. The modifications in the axonal structure and those of the myelin
      sheath determine modifications of the nervous excitability and conductibility.
      All the lesions we have pointed out in congenital megaureter participate in
      compromising of the peristaltic. Nervous and muscular structures lesions indicate
      a process of incomplete development of the ureter. They are structures that do
      not achieve functional maturation. We may consider congenital megaureter as a
      digenesis with hypoplasia.

PMID- 18060189
TI  - Venous circulation of the bronchial wall.
AB  - Bronchial supply plays an important role in both the protecting mechanisms and
      the pathogenic ones of many chronic inflammatory, infections or ischemic diseases
      of the lung. However, little is known regarding the bronchial supply development;
      the appearance of the connections to the functional pulmonary supply; the
      territory supplied by the bronchial veins. In this study, we follow the
      distribution of the pulmonary veins branches at the level of the subcarinal
      airways and their relationship to the bronchial veins in the human lungs. For
      studying the venous supply of the airways, we used the corrosion and colored
      gelatin injection methods followed by microdissection by means of an operator
      microscope. Venous circulation of the intrapulmonary airways is mainly tributary
      to the pulmonary vein branches. Venous circulation of the extrapulmonary airways
      is tributary to both the pulmonary and the bronchial veins. Taking into account
      the difference of sizes, we consider that, under physiologic conditions, the main
      venous collector is represented by the pulmonary veins.

PMID- 18060190
TI  - Mast cell reaction in malignant laryngeal neoplasm.
AB  - INTRODUCTION: Mast cells are normal connective tissue residents. Their densities
      vary from an organ to other, but are constantly well represented in respiratory
      tract. Mast cell hyperplasia was found in many malignant tumors, but the
      significance of this phenomenon is still unknown. In the literature, there are
      few data about mast cell reaction in malignant laryngeal neoplasm. MATERIAL AND
      METHODS: We studied archive blocks from 127 laryngeal carcinomas. For
      histological diagnosis two sections were prepared for Hematoxylin-Eosin staining
      and Alcian blue-Safranin histochemistry at pH 0.2 for identifying mast cells.
      Examination has been performed with Nikon Eclipse 600 microscope. Microscopic
      images were analyzed with Lucia G program. Microvessel density was calculated
      using the hot spot method. RESULTS: Most of the cases were squamous cell
      carcinoma G1 - 24.4%, G2 - 56.69%, G3 - 18.11%, and 0.78% adenoid cystic
      carcinoma. Invasive squamous cell carcinoma mast cell microdensity was 2.19 and
      4.66 in microinvasive squamous cell carcinoma. Mast cell microdensity in
      malignant laryngeal papillomatosis was 9.33 and 46.66 in adenoid cystic
      carcinoma. In carcinoma-associated mast cell hyperplasia, the large majority of
      mast cells were Alcian blue positive. CONCLUSIONS: In early stages, the mast
      cells are numerous (microinvasive squamous cell carcinoma mast cell microdensity
      4.66) and rare or even absent in late stages (invasive squamous cell carcinoma
      mast cell microdensity 2.19). Mast cell microdensity in malignant laryngeal
      papillomatosis was 9.33 and 46.66 in cystic carcinoma. Alcianophil mast cells are
      present in tumor area, and safraninophil mast cells are residents of connective
      and muscular tissue, at a distance from the tumor.

PMID- 18060191
TI  - Influencing vascular reactivity in vivo by histaminergic agonists and
      antagonists.
AB  - The eye is a target organ for the action of several topical or systemic drugs.
      The aim of the present study is to analyze the differences in reactivity between
      the iris and conjunctiva vessels after the topical administration of histamine
      and histamine receptor blockers respectively. Using a novel non-invasive
      technique for the quantification of the vascular diameters in the eye vessels,
      the response of these vessels to histamine, to H1 receptor blocker promethazine,
      and to H2 receptor blocker ranitidine versus vehicle (control) was analyzed. The
      results show differences in reactivity between iris and conjunctiva vascular
      territories. This data suggest that the population of histamine receptors differs
      between these two vascular areas.

PMID- 18060192
TI  - Hibernating myocardium, morphological studies on intraoperatory myocardial
      biopsies and on chronic ischemia experimental model.
AB  - Hibernating myocardium represent a prolonged but potentially reversible
      myocardial contractile dysfunction, an incomplete adaptation caused by chronic
      myocardial ischemia and persisting at least until blood flow restored. The
      purpose of this study was to investigate the morphological changes and weather
      relations exist among function, metabolism and structure in left ventricular
      hibernating myocardium. Material and methods. Experimental study is making on 12
      dogs incomplete coronary obstruction during six weeks for morphologic studies of
      ischemic zones. On 48 patients with coronary stenosis myocardial biopsies was
      effectuated during aorto-coronarian bypass graft. On 60 patients with valvular
      disease associated with segmental coronary atherosclerotic obstructions during
      surgical interventions on a effectuated repeatedly biopsies from ischemic zones.
      Dyskinetic ischemic areas was identified by angiography, scintigraphy, low dose
      dobutamine echography to identify the cells viability. On myocardial biopsies
      various histological, histoenzymological, immunohistochemical and ultrastructural
      methods were performed. RESULTS: The morphological cardiomyocytic changes can
      summarized: loss of myofilaments, accumulation of glycogen, small mitochondria
      with reversible lesions, decrease of smooth reticulum, absence of T tubules,
      depression of titin in puncted pattern, loss of cardiotonin, disorganization of
      cytoskeleton, dispersed nuclear heterochromatin, embryofetal dedifferentiation,
      and persistence of viability. Extracellular matrix is enlarged with early matrix
      protein such fibronectin, tenascin, fibroblasts. In experimental material the
      morphological changes present similarities with the human biopsies, but
      intermixed with postinfarction scar tissue. Redifferentiation of hibernanting
      cells end remodeling of extracellular matrix is possible after quigle
      revascularization through aorto-coronary bypass grafts.

PMID- 18060193
TI  - The arthroscopy-histological criterion link in endoscopic "repair" treatment of
      chondral and chondralbone lesions of the knee.
AB  - The authors present the results of optical microscopic studies of some lesions of
      cartilage and subchondral bone of the knee, the arthroscopy allowing this
      structure's biopsy during the endoscopic procedures. These histological criteria
      are very important estimation factors of long term results of these "repair"
      techniques, the microstructure showing the real biological status of these
      specific tissues.

PMID- 18060194
TI  - Dermatofibrosarcoma protuberans is CD117 negative even after extreme antigen
      retrieval conditions.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a malignant cutaneous tumor with a high
      rate of recurrence. Nevertheless, it responds to the drug Imatinib. The
      pathogenic mechanism why this drug works seems to be different to the inhibition
      of the Kit receptor of tyrosine kinase, since DFSP has repeatedly failed to
      express CD117 when immunohistochemically tested. Due to previous reports that
      claimed the presence of CD117 in DFSP, we designed a model of antigen retrieval
      under extreme conditions with two cases of DFSO from our archives. The slides
      were kept in the pressure cooker during 15 minutes (pH9). Moreover, the tissue
      was incubated with the primary antibody for 60 minutes. Three negative controls
      were also used. Even after the "over-retrieval" process, no convincing positivity
      was shown, although high background staining notably increased. We also discuss
      several alternatives that have been given in literature to explain the mechanism
      of how Imatinib works in DFSP.

PMID- 18060195
TI  - Darier disease and Hailey-Hailey disease.
AB  - Darier disease (DD) and Hailey-Hailey disease (HHD) are autosomal dominantly
      inherited genodermatosis, caused by mutations in ATP2A2 gene and ATP2C1
      respectively. We investigated clinical and laboratory two patients - a men with
      Darier disease and a woman with Hailey-Hailey disease. The patient with Darier
      disease has mucosal lesions and dental modifications associated with mild mental
      retardation. At Hailey-Hailey case, the skin lesions are associated with
      neuropsychiatric and endocrinologic disorders. In both cases, the mutation is
      inherited from parents. Even if this diseases have similar features, clinical,
      genetical and histopathological they are distinct entities.

PMID- 18060196
TI  - Clinical significance of a mysterious clival canal.
AB  - During routine osteology demonstration of the posterior cranial fossa we noticed
      a transverse bony canal in the middle third of the clivus of an adult male skull.
      The canal was situated 1.8 cm in front the anterior border of the foramen magnum.
      The length of the canal was 0.6 cm long. The possible embryological basis and
      clinical significance of the variation was discussed.

PMID- 18060197
TI  - The uterine carcinosarcoma - a case report.
AB  - The carcinosarcoma is a malignant mixed mullerian tumor with a highly malignant,
      biphasic tumor consisting of both epithelial and mesenchymal components. The
      presented case refers to a patient in climax with a vaginal bleeding. The Doppler
      echography highlights a polypoid mass, which prolapses in the cervical channel.
      The histopathological and immunohistochemical analysis of the surgically resected
      piece allowed the carcinosarcoma diagnosis. The uterine carcinosarcoma's
      incidence is rare, that is why this case is interesting taking in consideration
      the biphasic pattern of the tumor.

PMID- 18060198
TI  - Renal inflammatory myofibroblastic tumor - a new case report.
AB  - Renal inflammatory pseudotumor is uncommon, benign tumor that has been classified
      into separate group but there is a risk that this lesion could be misdiagnosed.
      The aim of this work is to report a new case of 57-years-old man presented in our
      hospital with hematuria, minimal grade fever and right flank pain. Magnetic
      resonance imaging (MRI) and sonography revealed a tumor of the right mediorenal
      parenchyma, 2.5 cm in diameter. The patient underwent right nephroureterectomy
      under the diagnosis of renal cell carcinoma. Macroscopically examination carried
      out on the removed kidney showed a 2/2/1.5 cm yellowish, gelatinous, well
      circumscribed, mediorenal and pericaliceal mass. Fragments of the tumor were
      fixed in 10% formaldehyde, included in paraffin, and the sections were stained
      with HE, VG and immunohistochemically with vimentin (VIM), MNF116, SyN, smooth
      muscle actin (ACT), desmin, CD68, S100, HMB45, and CD117. The histological
      examination revealed a compact spindle cell proliferation, a hypocellular fibrous
      area in an edematous myxoid background infiltrated by small lymphocytes,
      histiocytes, some plasma cells and small bone area. The spindle cells were
      diffuse positive for VIM, ACT, CD68 and negative for desmin, MNF116, SyN, S100,
      HMB45, and CD117. The pathologic diagnosis was renal inflammatory pseudotumor,
      raising the problem of differential diagnosis, as the clinical and imagistic
      aspects are similar to those of a renal carcinoma and the problem in establishing
      a preoperative correct diagnosis.

PMID- 18060199
TI  - Erythrokeratodermia variabilis - variant with circumscribed variable erythema and
      periorificial fixed Bazex Dupre erythema.
AB  - Erythrokeratodermia represents a group of rare genetic diseases characterized
      through disorders of keratinization. Clinically, they are presenting themselves
      with erythematous and hyperkeratosic lesions that can be persistent or variable
      as to their aspect and localization. They were classified in erythrokeratodermia
      variabilis (EKV) and erythrokeratodermia symmetric progressive (EKSP). We are
      presenting the case of a 9-years-old child which presents from birth facial and
      perioral erythema; erythematous and hyperkeratosic lesions with circinate
      character, extremely variable, localized especially on the anterior thorax (on
      the chest and in the axillar and inguinal folds). The neonatal debut, the
      clinical and histological aspect are suggestive elements for the EKV. In
      addition, the child has a plan frontal angioma and a congenital horizontal
      nistagmus. We realized a review of a literature data being different clinical
      variants of presentation of EKV and the eventual possible associations. It is
      considered the fact that the clinical presentation in the presented case
      corresponds to the variant of EKV with variable circinate erythema described by
      Bazex and Dupre. The case is also particular through the association of a plan
      frontal angioma, particularly of a congenital horizontal nistagmus, associations
      that we could not find in the literature.

PMID- 18060200
TI  - Drug-induced hepatitis - morphological and ultrastructural aspects.
AB  - Frequency of drug-induced liver diseases is increasingly, more than 200 different
      drugs being incriminated in hepatic disorders. We performed a retrospective study
      on 65 cases of deaths due to drug intoxications and an experimental model of
      subacute hepatitis induced by acetaminophen. In our experimental model, we
      observed various histological lesions: granular degeneration, vascular
      congestion, lymphoplasmocyte infiltration, cytonecrosis. Histological criteria
      are not specifically, but very usefully, because based on these criteria we can
      suspect a drug etiology in hepatic disorders when any other cause is absent.
      Ultrastructural study of hepatocytes revealed some modifications, in addition to
      data provided by optical microscopy.

PMID- 18060202
TI  - Islamic teachings of bioethics in relation to the practice of medical genetics.

PMID- 18060203
TI  - Towards safer surgery in patients with sickle cell disease.
AB  - Surgery in patients with sickle cell disease (SCD) has been associated with high
      morbidity and mortality. In recent years, a marked improvement in the safety of
      surgery and anesthesia in this high-risk group of patients has been witnessed;
      owing to the improvements in surgical and anesthetic care, greater awareness of
      pathophysiology of the disease, proper perioperative preparation, and attention
      to factors predisposing to vasoocclusive crises. However, this is not paralleled
      by similar improvement in countries where the disease is not prevalent. Greater
      population mobility in recent years makes recognition of surgical manifestations
      of the disease, and awareness of perioperative management of sickle cell patients
      undergoing surgical interventions of paramount importance. This article aims to
      summarize steps towards safer surgery in patients with SCD.

PMID- 18060204
TI  - Effect of panaxatriol on hematogenesis and granulocyte-macrophage colony
      stimulating factor in radiation injured mice.
AB  - OBJECTIVE: To assess the recovery effect of panaxatriol (PT) on myeloid
      hemopoiesis in radiation injured mice, and analyze the underlying mechanism.
      METHODS: This study was carried out in the Animal Center of Shandong University,
      Jinan, China, during March to September 2006. Forty-five inbred albino mice were
      separated randomly into 3 groups: control group, radiation group, and radiation +
      PT group (200 mg/kg/d, 3 weeks). Peripheral blood cells were detected by globuli
      meter, CD34+ cells in bone marrow were detected by flow cytometry, and the
      protein expression of granulocyte-macrophage colony stimulating factor (GM-CSF)
      was detected by immunocytochemistry. RESULTS: The numbers of peripheral blood
      cells and bone marrow CD34+ cells, and the expression of GM-CSF in the radiation
      group were lower than in the control group. After treatment with PT, the numbers
      of peripheral blood cells and CD34+ cells, and the expression of GM-CSF increased
      significantly. CONCLUSION: Panaxatriol can relieve myelosuppression induced by
      radiation injury. The abilities of regulating the expression of hemopoietic
      growth factor GM-CSF and promoting the maturation of bone marrow cells may be
      responsible for some of these beneficial effects.

PMID- 18060205
TI  - Osteoarthritis models after anterior cruciate ligament resection and medial
      meniscectomy in rats. A histological and immunohistochemical study.
AB  - OBJECTIVE: To compare the amount of degeneration based on the time spent, using 2
      different methods of surgically induced osteoarthritis (OA) that frequently used
      in treating OA. METHODS: We undertook this research in Ondokuz Mayis University,
      Surgical Research Center between April 2006 and July 2006. In this study, 55 rats
      were used, 7 as the control group, and 12 in each of 4 groups. We compared the
      amount of OA formed by the medial meniscectomy (MMx) and anterior cruciate
      ligament transection (ACLT) at 8 and 16 weeks according to the Modified Mankin
      Score and histologically and immunohistochemically due to their response to
      Matrix metalloproteinase 13 expression (MMP13). RESULTS: We observed the highest
      degeneration in the MMx model at 8 weeks, and this situation continued until 16
      weeks. However, the degeneration in the ACLT model was lower at 8 weeks compared
      with the MMx group, however, it reached the same amount as the MMX group at 16
      weeks. CONCLUSION: The OA model formed by the ACLT method was better than the MMx
      model when degeneration and time were taken into consideration and should be used
      when researching drugs on an experimental basis in OA.

PMID- 18060206
TI  - The potential anti-inflammatory effect of tetrahydrobiopterin administration in
      renal mass reduction-induced chronic renal failure in rats.
AB  - OBJECTIVE: To investigate the impact of tetrahydrobiopterin (BH4) supplementation
      on the markers of inflammation, and on the histological picture of the kidney in
      chronic renal failure C-reactive protein (CRF) induced in rats by subtotal
      nephrectomy (SNx). METHODS: This study was performed at the Faculty of Medicine,
      King Saud University, Riyadh, Saudi Arabia during the period from December 2005
      to January 2007. Chronic renal failure was induced by 5/6 SNx in 20 male Wister
      rats, and another 10 rats were sham operated by flank incision and served as
      controls. Ten SNx rats received 10mg kg-1 BH4 intraperitoneally daily for 4
      weeks. Plasma C-reactive protein (CRP), interlukin-6 (IL-6), malondialdehyde
      (MDA), and kidney functions were measured in all rats. Histopathological
      examination of the kidney tissues was also performed. RESULTS: Untreated CRF rats
      showed significant elevation of plasma CRP, IL-6, and MDA levels, and significant
      decrease in plasma albumin and total protein levels, tubuloglomerular fibrosis
      and, interstitial tubular infiltration with inflammatory cells in comparison with
      the sham-operated rats. Tetrahydrobiopterin treatment decreased CRP, IL-6, and
      MDA levels, and decreased tubuloglomerular fibrosis and interstitial inflammation
      in treated CRF rats. CONCLUSION: Supplementation with exogenous BH4 decreased
      markers of inflammation and protected the kidney against post-renal mass
      reduction histologic damage. Restoration of intracellular BH4 balance could
      normalize nitrous oxide production. Therefore, BH4 might be a promising strategy
      in attenuating inflammation in CRF. This may decrease endothelial dysfunction and
      limit the associated cardiovascular morbidity and mortality of this disease.

PMID- 18060207
TI  - Molecular testing of human papillomavirus in cervical specimens.
AB  - OBJECTIVE: To improve the diagnosis of cervical neoplasia by early detection of
      human papillomavirus (HPV) in uterine cervix, by adding molecular testing of HPV
      using hybrid capture 2 (HC2) and polymerase chain reaction (PCR) tests to
      Papanicolaou (Pap) test. METHODS: One hundred women were enrolled in this study.
      The mean age (mean +/- SD) was 41.97 +/- 8.76 years and the range was 27-65
      years. All women had undergone cervical cytological screening with cervical
      cytology, HPV DNA testing by HC2 and PCR, during the period from January -
      December 2006, at King Abdul-Aziz University Hospital (KAAUH) and King Fahd
      Research Centre, Jeddah, Saudi Arabia. RESULTS: The results we obtained by HC2
      for detection of HPV were 5 (5%) high-risk HPV, one low-risk HPV (1%) and 94
      (94%) negative cases. The PCR detected only 4 (4%) cases. Using the HC2 test as a
      reference, the sensitivity, specificity, positive predictive, negative predictive
      values and accuracy of baseline Pap were 50, 85, 17.7, 96.4, and 83%; of final
      Pap smear were 100, 96.8, 66.7, 100, 97%, and for PCR were 66.7, 100, 100, 97.9,
      and 98%. The Pap test was repeated within a year for patients with abnormal Pap
      or negative Pap test with positive HPV DNA. CONCLUSION: Combined screening by
      cytology and HPV testing using both HC2 and PCR sensitively detects women with
      existing disease. The absence of HPV DNA provides reassurance that patients are
      unlikely to develop cancer for several years. We suggest using Pap with HC2 and
      PCR in screening programs to ensure that women with the double negative result at
      baseline might safely be screened at longer intervals.

PMID- 18060208
TI  - Erythrocyte sedimentation rate in healthy first year medical students.
AB  - OBJECTIVE: To determine the reference value of erythrocyte sedimentation rate
      (ESR) in young healthy individuals following the standardized criteria of the
      International Committee for Standardization in Hematology. METHODS: The ESR was
      determined in a sample of 422 medical students of Karachi, Pakistan from the year
      1998 to 2004. After considering exclusion criteria, the data of 311 students (132
      males and 179 females) were analyzed. RESULTS: The reference values found in this
      study are 0-13 in the 1st hour for healthy young males and 0-40 mm in the 1st
      hour for healthy young female students. CONCLUSION: We suggest that the reference
      values for ESR should be determined for various segments of the local population.

PMID- 18060209
TI  - The role of ultrasonography and computed tomography in determining the etiology
      of ascites.
AB  - OBJECTIVE: To determine the role of ultrasonography (US) and computed tomography
      (CT) in the evaluation of ascites etiology. METHODS: From 2000-2006, patients
      admitted to the Radiology Department, Uludag University Medical School Hospital,
      Bursa, Turkey, were studied to determine the etiology of ascites, or those in
      whom ascites was determined during the course of other investigations were
      evaluated using US and CT. Existence of septa-debris, accompanying organ
      pathology, omental involvement, intestinal wall thickening, peritoneal implant,
      lymph node, diameter of portal vein, thickening of gall bladder wall, pleural
      effusion, collateral vascular structure, and cavernous transformation were also
      investigated. RESULTS: A total of 30 cases were included. Causes were determined
      to be malignant in 15 (50%) cases and 15 (50%) benign. The US was significantly
      superior to CT in the evaluation of gall bladder thickening. Omental thickening,
      thickening of intestinal wall, and peritoneal implant development were seen
      significantly more frequently in malignant compared to benign cases, while
      thickening of the gall bladder wall was seen more frequently in benign cases.
      Ascites density of malignant cases detected in slices without contrast was higher
      than in benign cases. The probability of malignancy was 98% when omental
      thickening, thickening of intestinal wall, and peritoneal implant were present
      together in the same case. CONCLUSION: Although CT and US may help to evaluate
      ascites, however, the differential diagnosis of ascites etiology remains a
      challenge.

PMID- 18060210
TI  - Is abandoning routine peritoneal cultures during appendectomy justified?
AB  - OBJECTIVE: To identify if there are any advantages of taking swab from the
      peritoneal fluid during appendectomy, and if it has any clinical implication on
      the progress of diseases. METHODS: Records of 160 patients who underwent
      appendectomy in Saqr Hospital, Rak, United Arab Emirates, from 2003 - 2005, and
      had culture and sensitivity from the peritoneal cavity were reviewed
      retrospectively. The macroscopic picture of the appendix, microorganism in
      peritoneal cultures, antibiotic, and the extent of using the result of the
      culture and sensitivity were evaluated. Patients with normal appendix who
      underwent laparoscopic appendectomy were excluded RESULTS: Patients age ranged
      from 4-55 years with male to female ratio of 4:1, all had prophylactic
      antibiotics and standard surgical procedures; 60% had perforated appendix, 13%
      were gangrenous. The most common organisms cultured were, Escherichia coli and
      bacteroids, rate of wound infection was 5%. None of the patients had their course
      of antibiotics adjusted in response to the result of the swab. CONCLUSION: Swabs
      from the peritoneal cavity during appendectomy do not have any clinical advantage
      especially with the empiric use of antibiotics and the short hospital stay.

PMID- 18060211
TI  - Infliximab "TNF-alpha antagonist" decreases intraabdominal adhesions.
AB  - OBJECTIVE: To evaluate the effect of infliximab on adhesion formation and it's
      associated morbidity and complications. METHODS: This study was performed in the
      Faculty of Medicine, Gazi University, Turkey between July 2005 and October 2005.
      Thirty-five rats were randomly divided into 4 groups. Laparotomy was performed in
      the Sham group (n=5), whereas cecal abrasion was carried out in all other groups.
      After cecal abrasion 0.9% sodium chloride was administered in the saline group
      (n=10), infliximab was administered to the study group (n=10) and nothing was
      administered to the last group (n=10). Adhesion formation was evaluated with
      macroscopic and microscopic adhesion scoring systems. Peritoneal fluid samples
      and mesenteric lymph node biopsies were taken to rule out bacterial peritonitis.
      Blood and peritoneal irrigation fluid samples were taken to measure the Tumor
      necrosis factor-alpha (TNF-alpha) levels. RESULTS: Macroscopic adhesion scores
      showed fewer adhesions in the infliximab group. The infliximab group had
      significantly fewer adhesions than the abrasion control and saline groups.
      According to the histological findings, there were no statistically significant
      differences between the groups. CONCLUSION: Early blocking of the activity of TNF
      alpha after cecal abrasion resulted in lower rates of adhesion formation,
      macroscopically. The TNF-alpha, a proinflammatory cytokine appears to be an
      important mediator for postoperative adhesion formation.

PMID- 18060213
TI  - Thorax deformity, joint hypermobility, and anxiety disorders.
AB  - OBJECTIVE: To evaluate the association between thorax deformities, panic
      disorder, and joint hypermobility METHODS: The study includes 52 males diagnosed
      with thorax deformity, and 40 healthy male controls without thorax deformity, in
      Tatvan Bitlis and Isparta, Turkey. The study was carried out from 2004 to 2006.
      The teleradiographic and thoracic lateral images of the subjects were evaluated
      to obtain the Beighton scores; subjects' psychiatric conditions were evaluated
      using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-1), and
      the Hamilton Anxiety Scale (HAM-A) was applied in order to determine the anxiety
      levels. Both the subjects and controls were compared in sociodemographic, anxiety
      levels, and joint mobility levels. In addition, males with joint hypermobility
      and thorax deformity were compared to the group with thorax deformity without
      joint hypermobility. RESULTS: A significant difference in HAM-A scores was found
      between the groups with thorax deformity and without. In addition, 21 subjects
      with thorax deformity met the joint hypermobility criteria in the group with
      thorax deformity, and 7 subjects without thorax deformity met the joint
      hypermobility criteria in the group without thorax deformity, according to
      Beighton scoring. The Beighton scores of the subjects with thorax deformity were
      significantly different from those of the group without deformity. Additionally,
      anxiety scores of the males with thorax deformity and joint hypermobility were
      found higher than males with thorax deformity without joint hypermobility.
      CONCLUSION: Anxiety disorders, particularly panic disorder, have a significantly
      higher distribution in male subjects with thorax deformity compared to the
      healthy control group. In addition, the anxiety level of males with thorax
      deformity and joint hypermobility is higher than males with thorax deformity
      without joint hypermobility.

PMID- 18060212
TI  - The efficacy of paracetamol in the treatment of ankle sprains in comparison with
      diclofenac sodium.
AB  - OBJECTIVE: To assess the efficacy of paracetamol in comparison with diclofenac
      sodium. METHODS: Between February - November 2006, a prospective, double blinded,
      parallel group study of 100 patients suffering from first or second degree
      lateral ankle sprain within 48-hours of admission in Tepecik Education and
      Research Hospital, Izmir, Turkey. Patients with bilateral injury, ipsilateral
      knee injury, third degree sprain, previous sprain within 6 months, and ankle pain
      less than 45 according to visual analogue score (VAS) were excluded. Patients
      rated pain on a 100 VAS, representing 0 no pain, 100 maximal pain. After
      enrollment, patients were randomized (1:1) with diclofenac sodium 150 mg/day or
      paracetamol 1500 mg/day for 5 days. Clinical assessments were carried out at
      baseline; on second, tenth days, and sixth week (end of study). In each visit,
      VAS and adverse effects of medication were questioned. RESULTS: The mean VAS of
      the diclofenac group was 81 and 82.3 with paracetamol group at the first visit.
      These scores decreased to 20.7, 9.9, 4.6 in diclofenac group and 11.9, 6.3, 3 in
      paracetamol group at the second, tenth days and last examination. Similar
      reductions in pain were observed at the end of study (p>0.05) in both groups.
      However, cases treated by paracetamol group showed accelerated decrease in VAS at
      day 2 and 10 in comparison with diclofenac group (p<0.05). Of the ankle range of
      motion, there was a similar improvement in both groups (39.6 degrees, 37.5
      degrees) (p>0.05). The incidence of gastrointestinal adverse effects on
      diclofenac group was much more than the paracetamol group, however, there was no
      significant difference (p>0.05). CONCLUSION: It was concluded that diclofenac
      sodium and paracetamol are effective and well tolerated as a short term treatment
      alternatives for acute ankle injuries.

PMID- 18060214
TI  - Delivery outcomes at term after one previous cesarean section.
AB  - OBJECTIVE: To determine the maternal and perinatal outcomes at term in women with
      one previous cesarean delivery and with no history of vaginal birth. METHODS:
      This is a case-control study conducted at King Abdul-Aziz University Hospital,
      Jeddah, Kingdom of Saudi Arabia, between January 1, 1999 and December 31, 2002.
      One hundred sixty-two women with one previous cesarean delivery and with no
      previous vaginal birth were compared with 324 control women. RESULTS: The
      cesarean section rate was higher in the study group 40 (24.7%) versus 23 (7.1%)
      in the control group and was statistically significant (p<0.001). Seventeen
      (10.5%) were induced with prostaglandin E2, and 33 (20.4%) required labor
      augmentation with oxytocin in the study, versus 22 (6.8%) and 21 (6.5%) in the
      control group. The duration of labor was longer in the study women compared to
      the control group (7.6 +/- 3.0 hours versus 6.0 +/- 2.3 hours), and this was
      statistically significant (p<0.001). There was one uterine dehiscence, and 2
      uterine ruptures in the study women, and none in the control group. Eight (1.65%)
      women had postpartum hemorrhage, 3 (0.62%) needed blood transfusion, and 7
      (1.44%) developed postpartum pyrexia. CONCLUSION: Women with no a prior history
      of vaginal delivery are considered less favorable, the vaginal birth after
      cesarean section success rate may be even lower if the indication for previous
      primary cesarean delivery was failure to progress, and may be associated with
      increased risk of uterine rupture. Further study is required to confirm our
      findings.

PMID- 18060215
TI  - Antibiotic resistance in children with complicated urinary tract infection.
AB  - OBJECTIVE: To determine the resistance of antibiotics for complicated urinary
      tract infection (UTI), including urinary tract anomaly (UTA), for empirical
      antibiotic therapy of complicated UTI. METHODS: Four hundred and twenty urine
      isolates were obtained from 113 patients with recurrent UTI, who used
      prophylactic antibiotics between February 1999 and November 2004 in the Eskisehir
      Osmangazi University, Eskisehir, Turkey. RESULTS: Reflux was found to be the most
      important predisposing factor for recurrent UTI (31.9%). Renal scar was detected
      more in patients with UTA than without UTA (59.2% versus 12.4%, p<0.05). Gram
      negative organisms were dominant in patients with and without UTA (91.5% and
      79.2%). Enterococci and Candida spp. were more prevalent in children with UTA
      than without UTA (p<0.001). Isolates were significantly more resistant to
      ampicillin, trimethoprim-sulfamethoxazole, amikacin, co-amoxiclav, ticarcillin
      clavulanate, and piperacillin-tazobactam in patients with UTA than without UTA.
      We found low resistance to ciprofloxacin and nitrofurantoin in UTI with and
      without UTA. Enterococci spp. was highly resistance to ampicillin and amikacin in
      patients with UTA. CONCLUSION: Aztreonam, meropenem, and ciprofloxacin seemed to
      be the best choice for treatment of UTI with UTA due to Escherichia coli and
      Klebsiella spp. Nitrofurantoin and nalidixic acid may be first choice antibiotics
      for prophylaxis in UTI with and without UTA. The UTI with UTA caused by
      Enterococci spp. might not benefit from a combination of amikacin and ampicillin,
      it could be treated with glycopeptides.

PMID- 18060216
TI  - Early outcome of children with complex atrial isomerism undergoing uni
      ventricular cardiac palliation.
AB  - OBJECTIVE: To review the postoperative intensive care unit (ICU) course and early
      outcome of children with complex atrial isomeric hearts undergoing cardiac
      surgery for uni-ventricular heart repair. METHODS: A retrospective review and
      analysis of ICU course of pediatric patients with atrial isomerism admitted from
      January 2000 to December 2004 in King Abdul-Aziz Medical City, Riyadh, Kingdom of
      Saudi Arabia, who underwent uni-ventricular repair. RESULTS: During the study
      period, 18 (n=18) patients were identified to have complex congenital heart
      disease (CHD) associated with atrial isomerism. They were in the form of right
      atrial isomerism (n=12), and left atrial isomerism (n=6). Eight patients did not
      meet the inclusion criteria of the study and were excluded. Ten of the 18
      patients fulfilled the study criteria and underwent first stage uni-ventricular
      heart repair with 8 survivals (80%). Three of the 8 operated survival cases
      underwent second stage repair with 2 survivals (66%) and one patient completed
      Fontan surgery with a good outcome. An uneventful ICU course was noted in 3 of 10
      operated patients (30%). Complications were noted in (40%) of cases including
      sepsis (n=4), tracheostomy (n=1), prolonged mechanical ventilation >7days (n=2).
      Over 50% of the operated patients required prolonged ICU stay (>2 weeks).
      CONCLUSION: Atrial isomerism is frequently associated with complex cardiac
      defects that often present in the neonatal stage and requires multiple staged
      cardiac surgeries. The surgical repair and peri-operative management of this
      group of patients can be difficult, challenging, and with potential risk of
      significant morbidity or mortality. In our setting, we found the outcome of
      children with atrial isomerism undergoing uni-ventricular palliation comparable
      to the literature.

PMID- 18060217
TI  - Exhaled breath condensate pH and hydrogen peroxide as non-invasive markers for
      asthma.
AB  - OBJECTIVE: To estimate the predictive value of exhaled breath condensate (EBC)
      hydrogen peroxide (H2O2) concentration and pH as non-invasive markers in asthma.
      METHODS: Fifty patients with unstable, steroid naive atopic asthma were included
      in the study, 25 with intermittent asthma and 25 with persistent asthma. Asthma
      diagnosis was according to the National Heart Lung and Blood Institute guidelines
      for the diagnosis and management of asthma. Forced expiratory volume in one
      second (FEV1) was measured by computerized spirometry. The EBC H2O2 assay was
      carried out using the colorimetric assay. The study was conducted from January to
      December 2005 in the Asthma and Allergy Center, Tikrit, Iraq. RESULTS: The EBC
      H2O2 concentration was higher in the asthmatic group (0.91 micromol) as compared
      with the control (0.23 micromol). There was an inverse correlation between EBC
      H2O2 concentration and FEV1 predicted percent for asthmatic patients. The mean
      EBC pH was lower in the asthmatic than the control group. There was a positive
      correlation between EBC pH and FEV1 predicted percent for asthmatic patients.
      There was an inverse correlation between EBC H2O2 concentration and pH for all
      asthmatic patients, intermittent, and persistent asthmatic groups. CONCLUSION:
      Exhaled breath condensate hydrogen peroxide concentration and pH was a good non
      invasive marker for asthma, whether it was with a persistent or intermittent
      course.

PMID- 18060218
TI  - Man-threatening viruses isolated from ticks in Saudi Arabia.
AB  - OBJECTIVE: To determine tick viruses transmissible to man in Saudi Arabia.
      METHODS: We collected tick samples for identification from different region of
      Saudi Arabia during March 1992 - December 1992. Ticks collected from domestic
      animals were washed with buffer containing antibiotics, macerated, triturated in
      minimal essential media (MEM), centrifuged and the supernatant inoculated
      intracerebrally in suckling mice. Brains of mice showing disease signs were
      similarly treated and the supernatant inoculated on cell cultures. Antigen spot
      slides were prepared from material of blind-passed cell cultures showing
      cytopathic effects. The slides were overlaid by group-specific hyperimmune mouse
      ascetic fluid (HMAF) to different virus groups and stained with antimouse
      fluorescein isothiocyanate conjugate. Positive slides were retested with
      monoclonal antibodies or HMAF to individual viruses within the positive group.
      RESULTS: Sindbis virus was isolated from Hyalomma dromedarii (H. dromedarii) from
      Al-Qasim and Jazan regions and Hyalomma impeltatum (H. impeltatum) from Al-Qasim,
      Ar-Riyadh and Jazan regions. Chick Ross and Kadam viruses were isolated from H.
      dromedarii from Al-Qasim region. Kadam virus was isolated from Hyalomma
      anatolicum (H. anatolicum) from Ar-Riyadh region. Dhori virus was isolated from
      H. impeltatum and Hyalomma schulzei (H. schulzei) from the Eastern region. Other
      alphaviruses were isolated from H. dromedarii from Al-Qasim and Tabuk regions, H.
      impeltatum from Jazan region, H. anatolicum from the Eastern region and
      Rhipicephalus sanguineus from Ar-Riyadh and Eastern regions. CONCLUSION: In the
      Kingdom, ticks harbor viral infections transmissible from wildlife to man and his
      livestock. Local physicians should be aware of the symptoms and signs of these
      infections.

PMID- 18060219
TI  - Prevalence of dyslipidemia in the Iraqi adult population.
AB  - OBJECTIVE: To establish the prevalence of dyslipidemia in the Iraqi adult
      population in Mosul, Iraq, according to the different recommended criteria.
      METHODS: The study was carried out from October 2003 to April 2004, with 871
      apparently healthy volunteers (413 males, 458 females) aged 20-70 year ([mean +/-
      SD] 41.2 +/- 13.8 year). Fasting blood specimens were collected from all subjects
      for measurement of serum lipid profile including triglycerides (TG), total
      cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density
      lipoprotein-cholesterol (LDL-C), and ratios of cholesterol such as TC:HDL-C, LDL
      C:HDL-C, and TG:HDL-C. Classification was carried out according to the different
      cut-off levels as recommended by the 2001 American National Cholesterol Education
      Program (NCEP) III using thresholds of TG > or = 150 mg/dl (2.0 mmol/L), LDL-C >
      or = 100 mg/dl (2.6 mmol/L), HDL-C<40 mg/dl (1.04 mmol/L), and non-HDL-C> or 130
      mg/dl (3.37 mmol/L). The criteria of the 1998 British Hyperlipidemia Association
      (BHA) were also followed using thresholds of TG > or =180 mg/dl (2.4 mmol/L), TC
      > or 194 mg/dl (5.0 mmol/L), LDL-C > or = 116 mg/dl (3.0 mmol/L), HDL-C< or =45
      mg/dl (1.15 mmol/L), TC:HDL-C> or =5.0, HDL-C:DL-C> or =2.5, and TG:HDL-C> or
      =3.0. RESULTS: Based on the American NCEP III criteria, the dyslipidemic states
      were noted with high TG (41.6%), high LDL-C (57.8%), low HDL-C (49.9%), and high
      non-HDL-C (56.8%) from the subjects. Based on the BHA criteria, high TG (24.5%),
      high TC (32.7%), high LDL-C (37.8%), high TC:HDL-C (30.9%), high LDL-C HDL-C
      (55.7%), and high TG:HDL-C (58.3%) were noted. CONCLUSION: Dyslipidemia is common
      in the Iraqi population, and this was identified at different recommendation
      criteria.

PMID- 18060220
TI  - The prevalence of abdominal obesity and its associated risk factors in married,
      non-pregnant women born and living in high altitude, southwestern, Saudi Arabia.
AB  - OBJECTIVE: To determine the prevalence of abdominal obesity and it's associated
      risk factors in a married, non-pregnant, high altitude female population.
      METHODS: A cross-sectional study conducted from January to March 2003, with 438
      currently married non-pregnant women aged 18-60 years, born and permanent
      residents in and around Abha, southwestern heights, Kingdom of Saudi Arabia. A
      questionnaire describing the demographic, social, reproductive, physical
      activity, and educational status was completed. The subjects were measured by
      weight, height, and waist circumference (WC). Body mass index (BMI) was
      calculated for each woman (BMI=weight [Kg]/height [m2]). Abdominal obesity was
      defined as WC>88cm, and total obesity as BMI > or =30 according to the World
      Health Organization criteria. RESULTS: The overall prevalence of abdominal
      obesity was 41.1%. The prevalence was positively and significantly associated
      with age, total obesity, and parity (p=0.0001 for all), negatively and
      significantly with educational level (p=0.0001), and negatively and
      insignificantly with strenuous physical activity (p=0.9). Results of multiple
      logistic analyses showed that age, total obesity, and educational level were
      independent risk factors for abdominal obesity. CONCLUSION: The study highlighted
      the high prevalence of abdominal obesity and showed that in addition to total
      obesity, intra-abdominal fat deposition is influenced by other lifestyle and
      reproductive factors. Community health education programs, which provide
      information on the high prevalence of abdominal obesity and its risk factor to
      all women, will be certainly justifiable, and prevention strategies should be
      implemented accordingly.

PMID- 18060221
TI  - Regional variations in the prevalence of consanguinity in Saudi Arabia.
AB  - OBJECTIVE: To report on the prevalence of consanguinity in each region of the
      Kingdom of Saudi Arabia including the variation in prevalence between urban and
      rural settlements. METHODS: The study was conducted over 2 years (2004-2005). A
      cross-sectional sample determined by multistage random probability sampling of
      Saudi households from each of the 13 regions of the Kingdom. As part of survey
      questionnaire, the mother of each household was asked on the relationship to her
      husband to choose one of 3 answers: first-degree cousin, more distant
      relationship, or no relation. RESULTS: The overall prevalence of consanguinity
      was 56% with the first-degree cousin (33.6%) being more common than all other
      relations (22.4%). The overall prevalence was significantly more common in rural
      (59.5%) than in urban settlements (54.7%) (p=0.000). There are regions with high
      prevalence of 67.2% such as Madina, and regions with significantly lower
      prevalence of 42.1% such as Al-Baha (p=0.000). CONCLUSION: The national
      prevalence of consanguinity in the Kingdom of Saudi Arabia remains high. In
      addition, there are significant variations in the prevalence of consanguinity
      between certain regions as well as between rural and urban settlements that
      should be taken into consideration in further studies.

PMID- 18060222
TI  - Prescribing pattern of general practitioners for osteoarthritis in primary care
      settings in Bolu, Turkey.
AB  - OBJECTIVE: To assess the drug preferences of primary care physicians for
      osteoarthritis (OA) in comparison with the current guidelines, and their
      reflections in the cost of prescriptions. METHODS: Data were collected from all
      primary health care centers in Bolu, Turkey, during November 2002 from patient
      polyclinic logbooks. Drugs prescribed were classified according to the Anatomical
      Therapeutic Chemical Classification system for comparison purposes. Gender, age,
      and health insurance of patients were analyzed for drug preferences and costs.
      RESULTS: Forty-eight primary care physicians prescribed 1,047 drugs for 507 OA
      patients with total a cost of $10,254. Anti-inflammatory and antirheumatic
      products were the leading group accounting for 59.6% of the prescribed drugs, and
      84.1% of the total expenditure. Paracetamol, the most commonly recommended in the
      guidelines, constituted 6.9% of all prescribed drugs and 0.9% of the total cost.
      Drug preferences showed a statistical difference among the health insurance types
      while drugs' cost showed statistical significance among the gender and health
      insurance types. Cyclooxygenase-2-specific inhibitors were the most commonly
      prescribed subgroup, constituting 23.2% of prescribed drugs and 62.6% of the
      total expenditure. CONCLUSION: Paracetamol in practice was not the first-line
      drug preferred by primary care physicians. Drug prescription data showed that the
      preference of drugs was affected by health insurance types and the gender of
      patients in favor of expensive, new drugs. There is a need for improvement of
      drug prescriptions to reflect current recommendations and guidelines.

PMID- 18060223
TI  - Serum resistin levels in Syrian obese patients with diabetes mellitus type II.
AB  - OBJECTIVE: To determine serum resistin levels in obese patients with diabetes
      mellitus type II. METHODS: We studied 87 subjects in an sectional study, divided
      into 3 groups: obese, obese diabetic and normal subjects. Their age, gender and
      body mass index were recorded. Serum resistin, insulin, glucose, cholesterol,
      high-density lipoproteins, low-density lipoproteins, triglyceride, urea and
      creatinine were measured. RESULTS: The mean +/- SD plasma resistin for the obese
      diabetic group is 7.32 +/- 3.74 ug/ml versus 4.25 +/- 1.77 ug/ml in the control
      group (p=0.021). Intro-group comparison of obese subjects (diabetics versus non
      diabetics) revealed higher levels of resistin, glucose, triglyceride, cholesterol
      and low density lipoproteins in diabetic subjects, but no statistically
      significant difference of high density lipoproteins. Furthermore, resistin
      correlated significantly and positively with body mass index (r = 0.375; p<0.05),
      resistin correlated significantly and negatively with high-density lipoproteins
      (r = -0. 363; p<0.05). CONCLUSION: Serum resistin levels are increased in obese
      patients with type 2 diabetes compared with controls. Resistin appears to be a
      possible link between obesity and type 2 diabetes in humans.

PMID- 18060224
TI  - Urofacial syndrome.
AB  - The urofacial or Ochoa syndrome is a rare disease. We report on 2 patients of
      middle-eastern origin, with a review of the current literature to further
      document the existence of this syndrome, and to increase the general awareness of
      the classical facial characteristics, which facilitates diagnosis.

PMID- 18060225
TI  - Gastrosplenic fistula in Hodgkin's lymphoma treated successfully by laparoscopic
      surgery and chemotherapy.
AB  - A gastrosplenic fistula is a rare complication of a gastric or splenic lesion. We
      report a case of Hodgkin's lymphoma nodular sclerosis involving the spleen that
      was complicated by spontaneous gastrosplenic fistula. The fistula was closed
      laparoscopically, and the patient underwent partial gastrectomy and gastric wall
      repair, followed by successful chemotherapy. This is also the first reported case
      in published literature where closure of gastrosplenic fistula and partial
      gastrectomy was carried out laparoscopically. We recommend that extensive open
      surgical procedures including total gastrectomy, splenectomy, and pancreatectomy
      may be avoided in the management of gastrosplenic fistula, and the patient could
      be managed by less radical, simple laparoscopic fistulectomy, with partial
      gastric resection. If the fistula is caused by a malignant process, the surgical
      repair should be followed by definitive treatment with chemotherapy and
      radiotherapy.

PMID- 18060226
TI  - Minimally invasive retroperitoneal adrenalectomy.
AB  - The minimally invasive MI approach has become the gold standard in removing the
      adrenal gland. Both transperitoneal and retroperitoneal techniques were reported
      safe and effective. The retroperitoneal approach has the advantage of direct
      access to the gland, easy access to retrocaval tumors, carries no cardiovascular
      or pulmonary risk of carbon dioxide insufflation to a high intra-abdominal
      pressure, and is not affected by previous abdominal surgery or radiation. We
      report a case of MI retroperitoneal adrenalectomy for right adrenal incidentaloma
      in a recently diagnosed breast cancer patient with multiple medical problems, and
      emphasize the advantage of this approach over the MI transperitoneal approach in
      the presence of patient's co-morbidity.

PMID- 18060227
TI  - Metastatic synovial sarcoma to the left atrium. A management dilemma.
AB  - We present a rare case of synovial sarcoma with minimal symptoms that
      metastasized and threatened to embolize the heart in a 26-year-old male admitted
      to our hospital for evaluation of low back pain. The tumor made a direct
      extension to the left atrium and moved freely in the left ventricle outflow
      tract. We discuss the potential therapeutic modalities in this difficult
      scenario.

PMID- 18060228
TI  - Multiple schwannomas of cauda equina in the absence of von Recklinghausen's
      disease.
AB  - Multiple schwannomas in the absence of neurofibromatosis is rarely reported in
      the literature. We present a 56-year-old female with a history of severe leg and
      back pain on the left side for one year. Magnetic resonance imaging revealed 4
      schwannomas located in the cauda equina in the absence of von Recklinghausen's
      disease.

PMID- 18060229
TI  - Pelvi-perineal myolipoma.

PMID- 18060230
TI  - Echocardiographic approach of left ventricular dysfunctions in essential
      hypertension.

PMID- 18060231
TI  - Tuberculosis verrucosa cutis. Experience from eastern Turkey.

PMID- 18060232
TI  - Constrictive pericarditis presenting as recurrent ascites for 10 years.

PMID- 18060233
TI  - Ultrastructure study of postmenopausal endometria of tibolone, conjugated
      estrogen + medroxyprogesterone acetate and tamoxifen users.

PMID- 18060234
TI  - Metformin discontinuation rate among patients with type-2 diabetes mellitus in
      Basrah, Iraq.

PMID- 18060235
TI  - Beaus lines.

PMID- 18060236
TI  - Study of the bacterial agents of blood stream infection in a Neonatal Intensive
      Care Unit.

PMID- 18060239
TI  - [Innovations in thrombolytic therapy in heart and coronary diseases].

PMID- 18060240
TI  - [Antithrombotic therapy of acute coronary syndromes].
AB  - Recent advances in the diagnosis and the treatment of acute coronary syndromes
      (ACS) have led to a substantial reduction of major coronary events, to an
      improvement in patient outcome and the definition of new guidelines. Current
      strategies for the treatment of patients with non-ST-elevation ACS recommend a
      combined antithrombotic therapy (including aspirin, clopidogrel, anticoagulation
      with low-molecular weight or unfractionated heparins or FXa-inhibitors or direct
      antithrombins and, eventually glycoprotein IIb/IIIa receptor antagonists). This
      combined antithrombotic therapy allows to increase the benefit of an early
      invasive strategy including coronary angiogram with stent percutaneous coronary
      angioplasty. The purpose of this review is to discuss and highlight the
      recommendations for the appropriate use of antithrombotic strategies in the
      setting of angioplasty in ACS patients.

PMID- 18060241
TI  - [Factor Xa-inhibition in interventional cardiology].
AB  - The recently established correlation between bleeding events and clinical
      outcomes in patients with coronary artery disease undergoing either non-invasive
      or invasive treatment for acute coronary syndromes (ACS) highlights the unmet
      need for safer anticoagulants that can be used in conjunction with dual or triple
      antiplatelet therapy. The central position of the coagulation factors IIa and Xa
      within the coagulation system account for their prominent role as targets for
      anticoagulants. Unfractionated heparin (UFH) achieves a variable indirect
      inhibition of both factors. The low molecular weight heparins (LMWH) show
      favourable pharmacokinetics over UFH and have a more pronounced activity against
      factor Xa as opposed to thrombin which may partially account for the benefits
      observed with LMWH in clinical trials. New agents that have been developed allow
      for a selective inhibition of factor Xa. Recently, exciting results have been
      reported with an indirect selective inhibitor of factor Xa in patients with ST
      elevation myocardial infarction (STEMI) -acute coronary syndromes (ACS) and non
      STEMI-ACS. In this article the pharmacology of the indirect selective factor Xa
      inhibitors Fondaparinux and Idraparinux will be discussed along with the direct
      selective factor Xa inhibitors DX-9065a and Otamixaban in the setting of
      interventional cardiology.

PMID- 18060242
TI  - [Direct thrombin inhibition in interventional cardiology. The ACUITY trial].
AB  - The direct thrombin inhibitor bivalirudin was tested in the ACUITY Trial 13 819
      patients with acute non-ST-segment elevation coronary syndrome in a prospective
      and randomized design. Three therapeutic regimens were compared in the context of
      an early invasive strategy: heparin plus glycoprotein IIb/IIIa inhibitor (GPI),
      bivalirudin plus GPI, or bivalirudin alone. Concerning the rate of ischaemic
      events bivalirudin alone was comparable to heparin plus GPI at a significantly
      lower rate of bleeding complications.

PMID- 18060243
TI  - [Platelet activation in acute coronary syndrome and interventional therapy].
AB  - Platelets play a critical role in formation of coronary thrombosis. An enhanced
      systemic platelet activation plays a significant role in the acute coronary
      syndrome. Despite better interventional techniques and better concomitant
      pharmacological therapy, the degree of platelet activation contributes
      significantly to prognosis and postinterventional event rate. Residual platelet
      activation after intervention is often associated with an enhanced initial
      platelet activation prior interventional treatment. An effective antiplatelet
      therapy is of utmost importance for the acute therapy and for secondary
      prevention in patients undergoing coronary interventions or with acute coronary
      syndrome. The efficacy of the antithrombotic therapy determines the long term
      prognosis in these patients.

PMID- 18060244
TI  - [Is stent thrombosis the new Achilles heel of interventional cardiology? State of
      the Art clinical trials, causes and approaches for prevention].
AB  - Coronary stents are the mainstay of percutaneous coronary intervention. Stent
      thrombosis is a potentially catastrophic and often life-threatening complication.
      If it occurs it presents in up to 80% as myocardial infarction, about half of the
      affected patients die from this complication. The dual antiplatelet therapy has
      markedly reduced its occurrence. Today, stent thrombosis occurs in <1%, usually
      as a delayed event; but compared to bare metal stents the overall incidence has
      not increased in meta-analyses of randomized trials. The advent of drug-eluting
      stents (DES) has raised concerns regarding the occurrence of delayed stent
      thrombosis. Delayed arterial wall healing as well as prothrombotic
      characteristics of the drug eluting stent itself may contribute to stent
      thrombosis. In order to prevent stent thrombosis a standardized fixed dose
      antiplatelet therapy with ASA and clopidogrel is recommended. But, their efficacy
      depends on patient's individual characteristics such drug metabolism. Therefore,
      individual determination of platelet function in each patient undergoing stent
      implantation may help to avoid prothrombotic as well as bleeding complications.

PMID- 18060245
TI  - [Prasugrel, a new thienopyridine].
AB  - The introduction of thienopyridines, specifically of clopidogrel, offered for the
      first time an orally active therapeutic alternative to acetylsalicylic acid (ASA)
      as an antiplatelet agent. Despite of established clinical efficacy, it became
      also evident with increasing clinical use that the antiplatelet actions of
      clopidogrel are subject of considerable interindividual variations of its
      antiplatelet efficacy (clopidogrel resistance) in laboratory tests which might
      also be clinically relevant. Prasugrel is a new, orally active thienopyridine
      with an expected spectrum of biological activities similar to clopidogrel.
      Prasugrel, like clopidogrel, is also an inactive prodrug that has to be
      transformed into the active metabolite by the liver cytochrome P450 system.
      However, different cytochromes appear to be involved for different extent in the
      generation of the active metabolite. The active metabolite of prasugrel, R
      138727, inhibits irreversibly the platelet P2Y(12) ADP receptor. In contrast to
      ASA, neither clopidogrel nor prasugrel inhibit the arachidonic acid metabolism.
      This allows synergistic interactions with ASA as thromboxane inhibitor and PGI(2)
      as stimulator of cAMP-formation in platelets. Prasugrel is orally more potent and
      acts more rapidly than clopidogrel, allowing lower oral dosing despite of similar
      in vitro activity of the active metabolites. These pharmacological advantages of
      prasugrel are probably due to its improved pharmacokinetics, i.e. the higher
      conversion rate of the prodrug into the active metabolite. In case of
      clopidogrel, only about 10-15% of the prodrug is converted into the active
      metabolite. This higher conversion rate possibly also explains the more rapid
      onset of platelet inhibition, the lower interindividual variability and higher
      oral potency with apparently less "resistance" than clopidogrel. Clinically, this
      might result in an improved efficacy. Whether this is associated with an
      increased risk of bleeding will be seen from the first phase III clinical trial
      in PCI-patients. The first results are expected at the end of the year.

PMID- 18060246
TI  - [Thrombolysis in cardiopulmonary resuscitation].
AB  - The prognosis of patients suffering cardiac arrest is still poor. Until today, no
      drug therapy has shown to improve longterm survival after cardiac arrest.
      Thrombolysis has been shown to be an effective therapy in patients with acute
      myocardial infarction (AMI) or massive pulmonary embolism (PE). Since 50-70% of
      cardiac arrests are caused by AMI or massive PE, the combination of
      cardiopulmonary resuscitation (CPR) and thrombolytic therapy appears to be
      sensible. As experimental studies have shown, thrombolytic therapy during CPR may
      not only be a causal treatment for coronary or pulmonary arterial obstruction by
      thrombi, but may also improve microcirculatory reperfusion after cardiac arrest.
      Although numerous small clinical studies have shown the efficacy of thrombolysis
      during CPR in selected patients, the generalized treatment of patients suffering
      cardiac arrest with thrombolytics can not be recommended based on current
      clinical evidence. According to the recent CPR guidelines, thrombolysis may be
      considered in cardiac arrest patients with suspected massive PE or as a so-called
      rescue therapy after unsuccessful conventional CPR in patients with a suspected
      thrombotic cause of cardiac arrest. The risk of severe bleeding complications
      following thrombolysis during CPR seems to be outweighed by the potential benefit
      of this therapy in selected patients.

PMID- 18060247
TI  - [Helping antibodies. Targeted antithrombotic and fibrinolytic therapy].
AB  - The development of monoclonal antibodies facilitated an enormous progress in
      modern medicine in the last years. The targeted inhibition of defined molecular
      structures allows therapeutic concepts, which before were inconceivable. There
      are numerous antibodies in clinical use within the area of tumour therapy,
      chronically inflammatory diseases, transplantation, infections and also in
      cardiovascular medicine. Different antibody formats are used such as IgG
      molecules, Fab fragments and single chain antibodies. Single chain antibodies
      represent the smallest functional form of the antibody and are used
      preferentially as recombinant antibodies. The therapeutic possibilities of
      antibody technology are extended by fusion to radioactive or therapeutically
      active substances. This review focuses on the application of antibodies and
      fusion proteins as antithrombotic and fibrinolytic drugs. The use of antibodies
      allows the development of inhibitory agents with clearly defined functional
      properties, as for example for activation-specific GPIIb/IIIa-blockade. In
      addition antibodies can be used for targeting antithrombotic and fibrinolytic
      agents to the thrombus, allowing an effective local action with less bleeding
      complications.

PMID- 18060248
TI  - [Inducing collaterals in due time. Arteriogenesis as a preventive principle].
AB  - A stimulation of collateral vessel growth is an attractive alternative
      therapeutic tool especially for patients with diffuse occlusive vessel disease.
      Extensive in vivo and in vitro studies in the preceding decades have led us to a
      thorough understanding of basic arteriogenic principles. Due to the timeline of
      naturally occurring arteriogenesis, a well-timed therapeutic induction appears to
      be limiting for effective proarteriogenic therapies in high-risk patients.
      Potential therapeutic approaches are based on a stimulation of monocyte function
      through cytokine application. First clinical studies have, nevertheless,
      demonstrated the limits of a unifactorial therapy. Therefore, a stimulation of
      the mechanical inductor of arteriogenic proliferation, i. e. fluid shear stress
      acting on the arteriolar endothelium, appears as a feasible therapeutic addition.
      Current results show the feasibility of that principle not only through active
      physical training, but also through passive application of an external
      counterpulsation (EECP), a method showing promising first results in the clinical
      setting.

PMID- 18060249
TI  - Extracellular RNA. A new player in blood coagulation and vascular permeability.
AB  - Upon vascular injury, locally controlled haemostasis prevents life threatening
      blood loss and ensures wound healing. Intracellular material derived from damaged
      cells at these sites will become exposed to cells and plasma proteins and could
      thereby influence vascular homeostasis, blood coagulation and defense mechanisms.
      Recently, this concept was documented by several studies indicating that
      extracellular nucleic acids, and RNA in particular, serve as promoter of blood
      coagulation in vivo and significantly increase the permeability across brain
      endothelial cells in vitro and in vivo. As procoagulant cofactor and "natural
      foreign material", RNA triggers the contactphase pathway of blood coagulation and
      thereby contributes to pathological thrombus formation. Administration of RNase
      significantly delayed occlusive thrombus formation and prevented edema formation
      in different animal models. Thus, extracellular RNA derived from damaged and
      necrotic cells may serve as a natural danger signal that contributes to
      initiation of host defense mechanisms, while antagonizing RNase provides new
      regimens for antithrombotic and vessel-protective therapies.

PMID- 18060250
TI  - Nucleic acid aptamers and their complimentary antidotes. Entering an era of
      antithrombotic pharmacobiologic therapy.
AB  - The translation of fundamental science-based constructs to the preemptive
      identification and optimal management of individuals with or those at risk for
      thrombotic disorders of the cardiovascular system has taken a step closer to
      being realized with the development of molecular technologies that include
      nucleic acid aptamers and their complimentary oligonucleotide antidotes. Herein,
      we summarize our experience with factor IX and von Willebrand factor aptamers,
      and introduce the era of antithrombotic pharmacobiologic therapy.

PMID- 18060251
TI  - Prevalence of bone mineral disease among adolescents with cystic fibrosis.
AB  - OBJECTIVE: To evaluate the prevalence of bone mineral disease among adolescents
      with cystic fibrosis and to relate the findings with the variables studied.
      METHODS: The study enrolled 37 adolescents who were assessed for: nutritional
      status according to height/age and body mass/age ratios; bone mineral density of
      the lumbar spine and entire body by densitometry with dual emission X-ray; daily
      dietary intake according to a 3-day dietary recall; and pulmonary function by the
      forced expiratory volume in one second test. RESULTS: Mean age was 13.2 (+/-2.8)
      years. Nutritional status was adequate in 70.3 and 75.7% of patients according to
      the height/age and body mass/age indices, respectively; 54.1% of the patients
      exhibited reduced lumbar spine bone mineral density and 32.5% for the whole body.
      There was a positive correlation between bone mineral density and body mass index
      (p = 0.04). Lung disease and pancreatic insufficiency exhibited a correlation
      with altered bone mineral density. The dietary recall revealed adequate
      percentages of calcium, phosphorous and calories, according to the nutritional
      recommendations laid out in the European Cystic Fibrosis Consensus. The
      multivariate analysis indicated that these variables were not statistically
      significant. CONCLUSIONS: There is a high prevalence of bone mineral disease
      among adolescents. Good nutritional status, pancreatic enzyme replacement and
      control of lung disease may have a protective effect on bone mass.

PMID- 18060253
TI  - Biochemical evaluation of glycemic levels of long-term tacrolimus therapy in
      rats.
AB  - One of the more serious complications following transplantation is the
      development of post-transplantation diabetes mellitus (PTDM), which has a major
      impact on the quality of life, with effects ranging from the control of glycemia
      times to increased susceptibility to infections and cardiovascular complications.
      It has been suggested that immunosuppressive therapy, mainly tacrolimus therapy,
      may be an important factor in the development of PTDM. There is a lack of studies
      that explore the effects of long-term tacrolimus on PTDM in animal protocols. The
      objective of this study was therefore to evaluate the effects of long-term
      therapy with tacrolimus in rats. One group was treated with tacrolimus, injected
      subcutaneously, in a daily dose of 1 mg/kg of body weight. The chosen dose was
      sufficient to achieve therapeutic tacrolimus serum levels. The experimental
      periods were 60, 120, 180 and 240 days. One group was used as control and
      received daily subcutaneous injections of saline solution during all periods. A
      tendency towards increased glycemia levels during the initial periods (60 and 120
      days) was observed. However, at 180 and 240 days, the glycemia levels were not
      statistically different from that of the control group of the same period. It may
      thus be concluded that the deleterious effects of tacrolimus therapy on glycemia
      may be a time-related side effect.

PMID- 18060254
TI  - Hypersensitivity to conventional and to nickel-free orthodontic brackets.
AB  - The aim of this study was to evaluate the allergenic potential of orthodontic
      brackets, comparing the cutaneous sensitivity provoked by metals present in
      conventional metallic brackets to that provoked by brackets with a low
      concentration of nickel, known as "nickel-free". A sample was selected from 400
      patients undergoing treatment in the orthodontic clinic of the Pontifical
      Catholic University of Minas Gerais (Belo Horizonte, MG, Brazil), in the period
      from the beginning of 2002 to the end of 2003. A cutaneous sensitivity patch test
      containing 5% nickel sulphate was used in 58 patients (30 males and 28 females),
      aged between 11 and 30, which were using fixed appliances with Morelli brackets
      in both arches. In a second phase, 30 days later, a comparative test of cutaneous
      sensitivity was applied to the whole sample with two types of test specimens, in
      the form of a disc. Two alloys were tested: discs composed of the alloy used in
      the construction of conventional brackets and discs composed of a nickel-free
      alloy. The internal part of the forearm was chosen for testing, and 20 test
      specimens of each experiment (corresponding to the twenty brackets of a complete
      fixed appliance) were applied. Of the 58 patients evaluated, 16 patients were
      sensitive to the patch test with 5% nickel sulphate. Out of these 16 patients, 12
      developed an allergic reaction to experiment 1 (test specimen with nickel), while
      in experiment 2, only 5 patients showed sensitivity to that sample. The McNemar
      test revealed that the nickel-free test specimens provoked less allergic reaction
      when compared with the conventional alloy (p=0.016).

PMID- 18060255
TI  - Dissolving efficacy of some organic solvents on gutta-percha.
AB  - The aim of this study was to evaluate the solubility of gutta-percha in four
      organic solvents used in endodontics. The solubility of gutta-percha (Dentsply)
      was assessed in xylol, orange oil, eucalyptol, chloroform and distilled water. A
      hundred and fifty samples of gutta-percha were prepared using a standardized
      stainless steel mould and divided into five groups for immersion in the different
      solvents tested and in distilled water (control group) for 2, 5 and 10 minutes.
      The means of gutta-percha dissolution in the solvents were obtained by the
      difference between the pre-immersion original weight and the post-immersion
      weight in a digital analytical scale (Gehaka-AG2000). Data were statistically
      analyzed by Analysis of Variance (ANOVA) and multiple comparisons with Scheffes
      test (p<0.05). The best solvency capacity was obtained with xylol. Chloroform,
      orange oil and eucalyptol presented similar results, and distilled water did not
      promote alterations in the gutta-percha.

PMID- 18060256
TI  - In vitro evaluation of the effectiveness of the chemomechanical preparation
      against Enterococcus faecalis after single- or multiple-visit root canal
      treatment.
AB  - The purpose was to assess the elimination of Enterococcus faecalis in vitro in
      human mandibular premolars after chemomechanical preparation with or without the
      use of a calcium hydroxide dressing. After 60 days of contamination with E.
      faecalis, the root canals were prepared using the Crown-Down technique combined
      with 2% chlorhexidine gel irrigation. Then, the specimens were divided into two
      experimental groups, treated in a single visit or in multiple visits, and two
      control groups. The multiple-visit group received a dressing with calcium
      hydroxide for 14 days (Calen) and the single-visit group did not receive any
      medication. In the two control groups, the canals were filled with BHI after
      chemomechanical preparation with 2% chlorhexidine gel or distilled water.
      Microbial samples were taken from the root canals for colony forming unit count
      for each phase of the treatment using sterile paper points inside the root canal
      lumen. Data were ranked and analyzed by the Kruskal-Wallis statistical test. The
      residual microbial colonies were then assessed. The results showed that
      chemomechanical preparation using 2% chlorhexidine gel with no intra-canal
      dressing reduced by 100% the E. faecalis contamination of the root canal lumen.
      The calcium-hydroxide group that received the 14-day intra-canal dressing allowed
      a small number of bacteria to grow between visits, but without statistical
      differences between groups.

PMID- 18060257
TI  - Prevalence of nonsyndromic oral clefts in a reference hospital in the state of
      Minas Gerais, Brazil, between 2000-2005.
AB  - The aim of the present study was to analyze the prevalence of nonsyndromic oral
      clefts in children receiving treatment at the Center for the Rehabilitation of
      Craniofacial Anomalies, Jose do Rosario Vellano University, Alfenas, MG, Brazil.
      All the data for the epidemiological study was retrieved from the files of 126
      pediatric patients with oral clefts without any additional malformation, who came
      to the center for treatment between 2000 and 2005. A predominance of clefts was
      observed in Caucasians, and the ratio of male to female was 1.3. Males were 2.57
      times more affected by cleft lip and palate (CLP) than females. CLP with a
      prevalence of 39.68% and isolated cleft lip (CL) with a prevalence of 38.09% were
      the most common anomalies, followed by isolated cleft palate (CP; 22.23%).
      Complete and unilateral CLP (26.19%) presented the highest prevalence, followed
      by incomplete and unilateral CL (23.81%). The present study presents the
      experience of a reference hospital in the state of Minas Gerais; however, the
      real prevalence of oral clefts in Brazil is still unknown. Our findings differ
      from those of a few previous Brazilian reports because they suggest similar
      prevalences of CLP and CL, and a higher prevalence of CLP in Caucasian males.

PMID- 18060258
TI  - Specific concentration evaluation of 16% carbamide peroxide compounded at
      dispensing pharmacies.
AB  - The aim of this work was to evaluate the concentration of carbamide peroxide
      compounded at different dispensing pharmacies. Immediate concentration analysis
      was made of bleaching gels dispensed by specialized pharmacies, and of a
      commercially available gel (control group) (n=20). The carbamide peroxide
      concentration was determined by titration and the results were analyzed
      statistically by the Kruskal-Wallis test. The commercial bleaching agent (control
      group) and one of the gels from the pharmacies presented the best mean
      concentration values, close to 16%. In conclusion, the concentration of the
      manipulated and industrialized carbamide peroxide gels presented concentration
      values differing from 16%.

PMID- 18060259
TI  - In vitro antimicrobial activity of irreversible hydrocolloid impressions against
      12 oral microorganisms.
AB  - This study evaluated in vitro the antimicrobial activity of irreversible
      hydrocolloids (one containing an antimicrobial agent) prepared with water or with
      a 0.2% chlorhexidine digluconate solution against 12 strains of the oral
      microbiota. Twenty specimens (0.5x1.0 cm) for each group (1. Jeltrate mixed with
      water; 2. Jeltrate mixed with 0.2% chlorhexidine digluconate solution; 3.
      Greengel mixed with water; 4. Greengel mixed with 0.2% chlorhexidine digluconate
      solution) were prepared under sterile conditions and placed in culture media
      inoculated with the indicator strains. After incubation in aerobiosis or
      microaerophilia, inhibition of the microbial growth was measured and the results
      were interpreted. The normal adherence curve revealed a non-normal distribution
      of the data, so the non-parametric Friedman Test was performed (p<0.05). The
      antimicrobial activity of the groups was classified in the following order: 1, 3,
      4, and 2. The results suggest that the method of preparing irreversible
      hydrocolloids with a 0.2% digluconate chlorhexidine solution is more effective
      than the incorporation of an antimicrobial agent in the powder to reduce cross
      contamination caused by impressions.

PMID- 18060260
TI  - New formula to objectively evaluate skeletal maturation using lateral
      cephalometric radiographs.
AB  - The aim of this study was to establish two new formulas for objectively
      evaluating skeletal maturation of cervical vertebrae in female and male Brazilian
      subjects using lateral cephalometric radiographs. The sample included 128 girls
      and 110 boys, aged 7.0 to 15.9 years, from the files of the Oral Radiology
      Clinic, Piracicaba Dental School, University of Campinas (Unicamp), SP, Brazil.
      The cervical vertebral bodies of C3 and C4 were traced and measured and
      regression formulas were developed in order to determine cervical vertebral bone
      age. Another sample of lateral teleradiographs and hand-wrist radiographs of 55
      girls and 54 boys (aged 7.0 to 15.9 years) was used to verify the reliability of
      the developed regression formulas, as compared with bone age assessed using the
      Tanner et al.15 (2001) Method (TW3) in hand-wrist radiographs. The analysis of
      both the boys and girls data (ANOVA) showed no statistical difference between
      cervical vertebral bone age, bone age, and chronological age, indicating that
      these formulas can be used in this population (p=0.5721 and p=0.6007 for girls
      and boys, respectively). Female cervical vertebral bodies of C3 and C4 increased
      in an accelerated manner from 10 to 13 years. Analysis of the male sample showed
      that C3 measurements increased in an accelerated manner from 12 to 15 years. The
      C4 measurements, however, did not increase at all. Using cervical vertebral bone
      age it is possible to evaluate skeletal maturation objectively in cephalometric
      radiographs.

PMID- 18060261
TI  - EBV-1 and HCMV in aggressive periodontitis in Brazilian patients.
AB  - The purpose of the present investigation was to compare the presence of Epstein
      Barr virus type 1 (EBV-1) and of Human Cytomegalovirus (HCMV) in crevicular fluid
      samples from deep and shallow periodontal pocket sites of Brazilian patients with
      aggressive periodontitis. A total of 30 systemically healthy patients with
      aggressive periodontitis participated in the study. Paper points were inserted
      into 2 gingivitis sites (<3 mm) and into 2 periodontitis sites (>5 mm) in each
      patient. PCR assay was used to identify genomic copies of HCMV and EBV-1. Twenty
      three patients (77%) were positive for EBV-1, while only 2 patients (6%) were
      positive for HCMV. The McNemar test revealed a positive association between EBV-1
      and periodontal lesions (p=0.043). Thirty-four (57%) out of 60 periodontitis
      sites were positive for EBV-1, whereas 18 (30%) gingivitis sites were positive
      (p=0.01). Only two sites (6.7%) were positive for HCMV. No positive association
      was found between HCMV and periodontitis or gingivitis (p=0.479). The elevated
      occurrence of EBV-1 DNA in periodontal pockets of patients with aggressive
      periodontitis supports a possible periodontopathic role of this virus.

PMID- 18060262
TI  - In vitro antimicrobial efficiency of a mouthwash containing triclosan/gantrez and
      sodium bicarbonate.
AB  - Several antiseptic substances have been used as adjuncts to routine mechanical
      procedures of oral hygiene, based on their antimicrobial effects. The objective
      of this study was to assess in vitro the antimicrobial efficiency of a mouthwash
      containing Triclosan/Gantrez and sodium bicarbonate in comparison to both
      positive and negative controls. Standard strain samples of Escherichia coli,
      Pseudomonas aeruginosa, Actinomyces viscosus and Bacillus subtilis were used.
      Samples of Streptococcus mutans and Gram-negative bacilli were collected from 20
      volunteers (10 with a clinically healthy periodontium and 10 presenting biofilm
      associated gingivitis). Evaluation of the antimicrobial activity was performed by
      determining the minimal inhibitory concentration (MIC). The results indicated
      that the test solution inhibited the growth of both Gram-negative and Gram
      positive microorganisms from the volunteers saliva as well as that of the
      standard strains at the MIC dilution of 1:20, whereas the MIC dilution of 0.12%
      chlorhexidine against the same bacteria was 1:80. Thus, even though the tested
      mouthrinse solution presented an in-vitro antimicrobial activity superior to that
      of a placebo, it was inferior to that of chlorhexidine.

PMID- 18060263
TI  - A retrospective clinical, radiographic and microbiological study of periodontal
      conditions of teeth with and without crowns.
AB  - The aim of this study was to evaluate retrospectively the periodontal conditions
      of teeth with fixed crowns that had been in place from 3 to 5 years before the
      study was conducted. Forty individuals were recalled for a follow-up visit. Full
      mouth clinical examinations were carried out and Visible Plaque Index (VPI),
      Gingival Bleeding Index (GBI), Probing Pocket Depth (PPD), and clinical
      attachment level (CAL) were assessed in 6 sites per tooth. Parallel radiographs
      were also taken and blindly analyzed by a digital caliper (distance between the
      apex and the bone crest). BANA tests were performed. A contra-lateral sound tooth
      was considered the control. Mean values were obtained and Wilcoxon and paired
      sample t tests were used to compare the test and control sites. Crowns had a mean
      VPI value of 30.42% as compared to 49.17% for sound teeth. The GBI was 33.33% and
      26.25% for test and control teeth respectively. Assessment of PPD revealed values
      of 2.30 and 2.14 mm, and assessment of CAL revealed averages of 2.02 and 1.89 mm
      for test and control teeth respectively. The mean values for radiographic
      distances were 12.73 and 13.67 mm, and for the BANA test, 67.50 and 50.00 for
      sound and crowned teeth, respectively. Statistically significant differences were
      observed for all parameters except for CAL and for the BANA test. It may be
      concluded that, with the methods used in the present study, crowns may be
      associated with more signs of inflammation, however not with periodontal
      breakdown.

PMID- 18060264
TI  - Electrognathographic evaluations of rehabilitated edentulous patients.
AB  - This study investigated, through computerized electrognathographic evaluations
      (K6-I Diagnostic System, Myotronics-Noromed Inc., Tukwila, USA), the mandibular
      movement pattern of 16 patients rehabilitated with complete dentures presenting
      no symptoms of stomatognathic functional alterations. The patients were
      instructed to wear an intra-oral appliance for occlusal plane coverage over their
      usual superior denture and were then rehabilitated with new dentures preserving a
      free-way space of 3 mm. After sixty days, the occlusal vertical dimension was
      increased and the modified inferior dentures were used for another 60 days. The
      obtained results were submitted to the Tukey Test and to the Friedman test,
      depending on which variable was under consideration, both at a significance level
      of 5%. The data revealed a significant decrease in free-way space when the first
      and the last evaluations were compared. No significant differences were found
      during opening and closing. It was concluded that the presence of a free-way
      space at the end of the treatment confirms the importance of its existence for
      maintaining the balance of the masticatory system, assuming the occurrence of a
      postural repositioning.

PMID- 18060265
TI  - Influence of the power level of an ultra-sonic system on dental cavity
      preparation.
AB  - The aim of this study was to evaluate the shape of dental cavities made with the
      CVDentus system using different ultrasound power levels. One standard cavity was
      made on the buccal aspect of 15 bovine incisors with a CVDentus cylindrical bur
      (82142). The sample was divided into three groups: G1-ultrasound with power II;
      G2-ultrasound with power III; and G3-ultrasound with power IV. A standardizing
      device was used to obtain standardized preparations and ultrasound was applied
      during one minute in each dental preparation. The cavities were sectioned in the
      middle, allowing observation of the cavity's profile with a magnifying glass, and
      width and depth measurement using the Leica Qwin program. The Kruskal-Wallis
      (p<0.05) and Dunn statistical analyses demonstrated differences between the
      dental cavity shapes when powers III and IV were used. However, the cavities that
      were made with power III presented dimensions similar to those of the bur used
      for preparation. We concluded that the power recommended by the manufacturer
      (III) is the most adequate for use with the CVDentus system.

PMID- 18060266
TI  - Streptococcus mutans-induced secondary caries adjacent to glass ionomer cement,
      composite resin and amalgam restorations in vitro.
AB  - The aim of this study was to define, in vitro, the potential to inhibit secondary
      caries of restorative materials currently used in dental practice. Standard
      cavities were prepared on the buccal and lingual surfaces of fifty extracted
      human third molars. The teeth were randomly divided into five groups, each one
      restored with one of the following materials: glass ionomer cement (GIC);
      amalgam; light-cured composite resin; ion-releasing composite; and light-cured,
      fluoride-containing composite resin. The teeth were thermocycled, sterilized with
      gamma irradiation, exposed to a cariogenic challenge using a bacterial system
      using Streptococcus mutans, and then prepared for microscopic observation. The
      following parameters were measured in each lesion formed: extension, depth, and
      caries inhibition area. The outer lesions developed showed an intact surface
      layer and had a rectangular shape. Wall lesions were not observed inside the
      cavities. After Analysis of Variance and Component of Variance Models Analysis,
      it was observed that the GIC group had the smallest lesions and the greatest
      number of caries inhibition areas. The lesions developed around Amalgam and
      Ariston pHc restorations had an intermediate size and the largest lesions were
      observed around Z-100 and Heliomolar restorations. It may be concluded that the
      restorative materials GIC, amalgam and ion-releasing composites may reduce
      secondary caries formation.

PMID- 18060267
TI  - Quality of life in patients submitted to surgical treatment for minor salivary
      gland neoplasms.
AB  - This study was aimed at assessing the quality of life in patients submitted to
      surgical treatment for minor salivary gland neoplasms (MSGN). Twelve patients (10
      women and 2 men, mean age: 49.4 years) with histopathologic diagnosis of
      pleomorphic adenoma (PA, 3 cases), polymorphous low-grade adenocarcinoma (PLGA, 2
      cases), cystic adenoid carcinoma (CAC, 4 cases), and muco-epidermoid carcinoma
      (MEC, 3 cases) were evaluated. All of them were treated by surgical excision;
      patients with CAC received radiotherapy as well. The patients quality of life was
      evaluated through a self-administered questionnaire concerning their physical
      well-being, emotional status, normal daily activities, and family relationships.
      The results showed that patients with MEC--the youngest among all patients-
      reported a significantly greater worsening of their physical well-being and
      emotional status after treatment as compared with patients treated for PA
      (P<0.05), and also of their functional activities as compared with those treated
      for PA and PLGA (P<0.05). In conclusion, age of development of the neoplasm and
      type of disease produce more impact on patients quality of life than does the
      therapys degree of aggression.

PMID- 18060268
TI  - MELD score, step forward to justice of liver graft allocation in Brazil.

PMID- 18060270
TI  - [Response to hepatitis B vaccine in alcoholics without clinically evident liver
      cirrhosis].
AB  - BACKGROUND: Alcoholics have higher prevalence of hepatitis B virus (HBV)
      infection than non-alcoholics and such fact may influence in the development of
      liver cirrhosis and/or hepatocellular carcinoma. AIM: To evaluate the response to
      hepatitis B vaccine in alcoholics without liver cirrhosis. METHODS: Twenty male
      alcoholics with mean age of 46.6 +/- 10.9 years were vaccinated; they ingested
      more than 80 g of ethanol/day for more than 10 years. As control group 40 male
      non-alcoholics with mean age of 37.8 +/- 9.7 years were also vaccinated. No
      serological evidence of contact with HBV, hepatitis C virus or human
      immunodeficiency virus was found among the subjects of both groups. The vaccine
      Euvax B (20 microg) was administered intramuscularly into the deltoid area at 0,
      1 and 6 months. Serum anti-HBs were determined after one month of the last dose.
      Levels <10 mUI/mL were considered as non-response, between 10 and 99 mUI/mL as
      seroconversion, and > or = 100 mUI/mL as seroprotection. RESULTS: No significant
      difference was found between alcoholics and controls, respectively, in the
      frequency of non-response (35.0% vs 32.5%), seroconversion (15.0% vs 15.0%) and
      seroprotection (50.0% vs 52.5%). Among responders, mean levels of anti-HBs in
      alcoholics (511 +/- 448 mUI/mL) were similar to the controls (696 +/- 410
      mUI/mL). No negative interference on the response was associated with the body
      mass index, tabagism, being drinking or concurrent chronic pancreatitis without
      pancreatic insufficiency. CONCLUSIONS: Male alcoholics without liver cirrhosis
      had similar frequency and serum levels of anti-HBs to the non-alcoholics in
      response to HBV vaccination.

PMID- 18060269
TI  - [Hepatocellular carcinoma: impact of waiting list and pre-operative treatment
      strategies on survival of cadaveric liver transplantation in pre-MELD era in one
      center in Brazil].
AB  - BACKGROUND: Liver transplantation is the main treatment option for hepatocellular
      carcinoma in patients with cirrhosis. AIM: Three months and 3 years survival were
      analysed in patients with cirrhosis and hepatocellular carcinoma and in patients
      with only cirrhosis. METHODS: Charts of patients subjected to cadaveric liver
      transplantation at the Clinical Hospital of the Federal University of Parana,
      Curitiba, PR, Brazil, between January 5th of 2001 and February 17th of 2006 were
      reviewed. Patients were divided into two groups for 3 months and 1 year survival
      analysis: cirrhosis and hepatocellular carcinoma and cirrhosis only. The two
      groups were also compared in relation to donor and recipient sex and age,
      etiology of cirrhosis, Child-Pugh and MELD scores at the time of the
      transplantation, warm isquemia time, cold isquemia time, units of red blood cells
      transfused during the transplantation, intensive care unit stay and total
      hospital stay. RESULTS: One hundred and forty six liver transplantation patients
      were analysed: 75 were excluded because of incomplete data and 71 were included.
      General 3 months and 1 year survivals were 77,4% and 74,6% respectively. Patients
      with hepatocellular carcinoma (n = 12) presented 3 months and 1 year survivals of
      100%. These rates were significantly higher than those of patients without
      hepatocellular carcinoma (n = 59; 72,8% and 69,4%). Mean MELD score, mean Child
      Pugh score and mean number of red blood cells transfused were significantly
      higher in patients without hepatocellular carcinoma. In this group it was also
      observed more Child-Pugh B and C patients and the diagnosis of cirrhosis because
      other causes. The rate of Child-Pugh A and hepatitis C was higher in patients
      with hepatocellular carcinoma. The two groups were identical in all other
      parameters analysed. CONCLUSION: Patients with cirrhosis and hepatocellular
      carcinoma presented better 3 months and 1 year survival rates than patients with
      only cirrhosis. This is possibly due to an early stage of cirrhosis at
      transplantation of patients with hepatocellular carcinoma.

PMID- 18060271
TI  - [Platelet indices in chronic alcoholic liver disease patients with
      thrombocytopenia].
AB  - AIM: To detect alterations in platelet indices in patients with chronic alcoholic
      liver disease and thrombocytopenia, and its correlation with other haematological
      parameters. METHODS: We studied 65 individuals separated in two groups: controls
      (n = 35) and chronic alcoholic liver disease patients with thrombocytopenia (n =
      30). The control group was age and gender matched with patients group. In all,
      controls and patients, a haematological evaluation was done, including platelets
      indices. RESULTS: In the patients group we found a low number of erythrocytes,
      leucocytes and platelet when we compare with controls. The same is true when we
      compare haemoglobin, hematocrit and absolute count of lymphocyte and neutrophil.
      The mean globular volume, mean globular haemoglobin and red cell distribution
      width where significantly higher in patients group. Platelet indices showed a
      statistical significant increased in platelet distribution width and decreased in
      platelet crit in the patient group. No differences where found on mean platelet
      volume between the two groups. Correlation between platelet number and other
      haematological parameters was found. CONCLUSION: Chronic alcoholic liver disease
      patients showed a decrease in all haematopoietic cell lines, probably associated
      with hypersplenism found in those patients. Additionally to the numeric
      alterations the erythrocyte and platelets showed morphologic alteration revelled
      by respective indices.

PMID- 18060272
TI  - [Relapse of alcohol consumption in liver transplant candidates. Risk factor
      analysis].
AB  - BACKGROUND: Alcohol relapse after transplantation is a serious concern in
      transplant centers and is a subject of controversy and debate. AIM: To evaluate
      the relapse of alcohol ingestion and the eventual associated factors in cirrhotic
      patients referred for liver transplantation. METHODS: A retrospective study
      comprised of 90 adult patients with liver cirrhosis, listed for transplant. The
      exclusion criteria were: not having at least 6 months of abstinence and release
      not approved by the psychology team. The diagnosis of relapse (ingestion of any
      quantity of alcohol) was done based on the information in the patients histories
      and those provided by telephone contact. RESULTS: The rate of relapse was of
      18.9%. This corresponded to 14.6% of the total number of men and 62.5% of the
      total number of women. Race, mean age, classification of hepatic dysfunction,
      time of alcoholism, quantity of alcohol ingested and the execution of transplant
      did not show significant correlation to alcohol relapse. The comparison between
      time of abstinence and relapse had an inversely proportional correlation.
      CONCLUSION: Relapse of alcohol consumption was low. Being of the female gender
      and having less than 1 year of abstinence has an influence upon alcohol relapse.

PMID- 18060274
TI  - [Crohn's disease small bowel strictureplasties: early and late results].
AB  - BACKGROUND: Strictureplasty is an alternative surgical procedure for Crohn's
      disease, particulary in patients with previous resections or many intestinal
      stenosis. AIM: To analyze surgical complications and clinical follow-up in
      patients submitted to strictureplasty secondary to Crohn's disease. METHODS:
      Twenty-eight patients (57.1% male, mean age 33.3 years, range 16-54 years) with
      Crohn's disease and intestinal stenosis (small bowel, ileocecal region and
      ileocolic anastomosis) were submitted to strictureplasty, at one institution,
      between September 1991 and May 2004. Thirteen patients had previous intestinal
      resections. The mean follow-up was 58.1 months. A total of 116 strictureplasties
      were done (94 Heineke-Mikulicz--81%, 15 Finney--13%, seven side-to-side ileocolic
      strictureplasty--6%). Three patients were submitted to strictureplasty at two
      different surgical procedures and two in three procedures. RESULTS: Regarding to
      strictureplasty, postoperative complication rate was 25% and mortality was 3.6%.
      Early local complication rate was 57.1%, with three suture leaks (10.7%) and late
      complication was present in two patients, both with incisional hernial and
      enterocutaneous fistulas (28.6%). Patients remained hospitalized during a medium
      time of 12.4 days. Clinical and surgical recurrence rates were 63% and 41%,
      respectively. Among the patients submitted to another surgery, two patients had
      two more operations and one had three. Recurrence rate at strictureplasty site
      was observed in 3.5%, being Finney technique the commonest one. Presently, 19
      patients had been asymptomatic with the majority of them under medical therapy.
      CONCLUSION: Strictureplasties have low complication rates, in spite of having
      been done at compromised site, with long term pain relief. Considering the
      clinical course of Crohn's disease, with many patients being submitted to
      intestinal resections, strictureplasties should be considered as an effective
      surgical treatment to spare long intestinal resections.

PMID- 18060273
TI  - [Crohn's disease and kidney stones: much more than coincidence?].
AB  - BACKGROUND: Crohn's disease is an inflammatory bowel disease associated with a
      wide variety of complications and manifestations secondary to the effects of
      underlie inflammatory process. In about 30% of the patients with Crohn's disease
      can be found extra-intestinals symptoms. Nephrolithiasis is one of them and the
      appearance of kidney stones, mainly of oxalate of calcium, is more common in
      these patients than in general population. AIM: To evaluate urinary metabolic
      factors potentially involved in renal stones formation on patients with Crohn's
      disease. METHODS: We evaluated 29 patients with Crohn's disease followed in the
      Outpatient Bowel Inflammatory Disease Clinics of State University Hospital,
      Londrina, PR, Brazil, from January to December of 2004. The metabolic evaluation
      included measured of blood and urine substances related to renal stones
      formation, kidneys, ureters and bladder ultrasonography and calculation of
      urinary supersaturation for calcium oxalate, uric acid and calcium phosphate.
      RESULTS: Twenty-nine of the evaluated patients were female or 65.5% and 34.5%
      were males. Among the metabolic urinary studied, we identified the following
      potential disturbances associated with nephrolithiasis: hypocitraturia in 21
      patients (72.4%), hypomagnesuria in 12 (41.4%), hyperoxaluria in 4 (13.6%) and
      urinary volume low in 5 (17.2%). Renal stones were identified in 13 patients
      (44.8%). Oxalate urinary excretion was higher in patients submitted to bowel
      surgery and also in patients with ileum resection. The urinary supersaturation of
      calcium oxalate and brushita in patients with bowels surgery was higher than the
      other patients not submitted to any surgery. Data to compare patients who
      underwent to surgery or not were analyzed by Mann-Whitney test (U test), and Qui
      square test or the accurate test of Fisher have been used to determine variables
      association. For all tests 5% of significance level was considered. CONCLUSION:
      This study shows that the frequency of renal stones in patients suffering from
      Crohns disease is higher than in general population and, also, higher than that
      described elsewhere for this disease. We identified hypocitraturia and
      hypomagnesiuria as the main factors which could explain our data. The impact of
      these metabolic disturbances can be also evaluated by means of the high
      supersaturation obtained for calcium oxalate and calcium phosphate which suggests
      the way those factors could be influencing crystal nucleation and, consequently,
      lead to renal stones formation in this group of patients.

PMID- 18060275
TI  - [Mechanical-thermal stimulation of the palatoglossus pillars].
AB  - BACKGROUND: The palatoglossus pillars were admitted as the main receptive
      responsible area by the pharyngeal swallowing reflex produced by food and tongue
      posterior progression. This concept sustain the mechanical-thermal maneuver used
      to recovery the committed pharyngeal function. A pharyngeal motor answer by
      pillar stimulation is common accepted but not unanimously. AIM: To verify the
      possible pharyngeal motor answers by palatoglossus pillars mechanical thermal
      stimulation. METHODS: Healthy volunteers are more able to provide effective
      reflex answers by pillars stimuli than patients. In this way we evaluated 51
      healthy adult volunteers from both sexes reproducing the pillars stimuli using
      metallic probe. The cold condition was obtained by probe immersion in water
      maintained to 10 degrees C. RESULTS AND CONSIDERATIONS: The study showed that the
      mechanical thermal stimuli over pillars was not able to produce any active answer
      linked to the swallowing pharyngeal phase. It is possible that literature
      observed answers were due to the gag reflex inadequately interpreted or
      unconscious voluntary contractions effort produced by the opening mouth and
      tongue externalization during the pillars exposition to execution of the
      mechanical thermal stimulation maneuvers.

PMID- 18060276
TI  - Gender effect on the clinical measurement of swallowing.
AB  - BACKGROUND: Swallowing coordination is affected by cortical and subcortical
      inputs from the central nervous system. Our hypothesis is that the swallowing
      dynamics may be influenced by gender. AIM: To evaluate the influence of gender on
      water swallowing dynamics. METHODS: We studied 111 health subjects, 36 men, aged
      24-77 years (mean: 46.3 +/- 16.1 years) and 75 women, aged 22-75 years (mean:
      39.6 +/- 13.3 years). All volunteers swallowed in triplicate 50 mL of water at 4
      degrees C while precisely timed, when we measured the time to swallow all the
      volume and counted the number of swallows. We calculated the inter-swallow
      interval: the time to complete the task, in seconds, divided by the number of
      swallows; swallowing velocity: volume drunk (mL) by the time taken (s);
      swallowing volume capacity: volume drunk (mL) divided by the number of swallows.
      RESULTS: Women had a shorter inter-swallow interval, slower swallowing velocity
      and lower volume capacity than men. CONCLUSION: Gender has an effect on water
      swallowing dynamics, with women having a lower swallowing velocity and a lower
      volume capacity in each swallow than men.

PMID- 18060277
TI  - Quantitative and qualitative analysis of collagen types in the fascia
      transversalis of inguinal hernia patients.
AB  - BACKGROUND: Inguinal hernia is the second most common surgical case in our field.
      The anatomical factors alone are not enough to explain the inguinal hernia.
      Studies show changes in the proportion and quantity of collagen fibers in the
      developing of inguinal hernia. The greater production of collagen type III
      compared to the type I could justify the thinning of the fascia transversalis and
      its weakness. AIM: To determine the quantitative and qualitative changes of
      collagen in the fascia transversalis in inguinal hernia patients and compare them
      to findings from corpses without inguinal hernia. METHOD: Prospective case
      control study based on the biopsy of fascia transversalis of 27 patients and 24
      corpses. The technique used was hematoxylin-eosin and picrosirius colorimetry.
      RESULTS: The medium percent area of collagen (types I + III) and collagen type I,
      in both groups, show no statistic difference. The quantity of collagen type III
      was greater in the patients. Patients classified with Nyhus IIIa presented
      greater quantity of collagen type III. CONCLUSION: There is no significant
      difference in the quantity of collagen in the fascia transversalis of patients
      compared to the controls. An increase in the quantity of collagen type III was
      found in patients with inguinal hernia and a greater quantity in those patients
      classified with Nyhus IIIa.

PMID- 18060278
TI  - CA72-4 antigen levels in serum and peritoneal washing in gastric cancer.
      Correlation with morphological aspects of neoplasia.
AB  - BACKGROUND: Determining levels of tumor markers in peritoneal washing enables
      likelihood of peritoneal recurrence to be ascertained in patients with high
      marker levels, thereby allowing provision of more accurate adjuvant treatment and
      postoperative follow up. AIM: To analyze the relationship between levels of tumor
      marker CA72-4 in serum and peritoneal washing, and morphological aspects of
      gastric carcinoma. METHOD: This study analyzed 32 consecutively-operated patients
      with gastric carcinoma, who underwent subtotal, total or palliative gastrectomy.
      The variables studied were CA72-4 levels in serum and peritoneal washing, lesion
      site, stage, degree of cell differentiation, operation performed, and number of
      extirpated and involvement lymph nodes. Of the 32 patient sample, 21 (65.6%) were
      male and 11 (34.4%) female. Mean age was 62.6 +/- 14.2 years (29 to 91 years).
      Following anesthetic induction, peripherical venous blood was collected through
      percutaneous punction of an upper limb vein. After the procedure, 50 mL of
      physiologic solution at 37 degrees C was introduced into the cul-de-sac. A 10 mL
      volume of this liquid was aspirated from the cavity and the peritoneal washing
      tested for CA72-4 levels. Normal values for CA72-4 levels in serum were
      considered < or =7 U/mL and high levels as >7 U/mL, whilst for the peritoneal
      washing normal levels were < or =0.61 U/mL, and abnormal >0.61 U/mL. RESULTS:
      Mean pre-operative serum levels for CA72-4 were 6.55 U/mL +/- 15.30 (0.3 to 75.30
      U/mL) whilst the mean level of CA72-4 in peritoneal washing was 8.50 U/mL +/-
      26.72 (0.3 to 142.00 U/mL); correlation between these levels was significant.
      Lymph nodes involvement by the gastric carcinoma correlated significantly with
      higher CA72-4 levels in both serum and peritoneal wash. There was no
      statistically significant correlation between serum level of CA72-4 and invasion
      into serosa by the gastric carcinoma. There was however, significant correlation
      between peritoneal washing levels of CA72-4 and involvement of serosa by gastric
      carcinoma. There was also a significant correlation between more advanced stages
      of gastric carcinoma and higher levels of CA72-4 in the peritoneal washing,
      although serum levels of CA72-4 and more advanced stage of gastric neoplasia
      showed no significant correlation. Degrees of cellular differentiation in the
      gastric carcinoma did not differ significantly with CA72-4 levels in serum or
      peritoneal washing. CONCLUSION: High levels of CA72-4 in peritoneal washing
      correlated significantly with lymph node metastasis and serosa involvement by the
      neoplasia, and also with more advanced stage of gastric carcinoma. The levels of
      CA72-4 in the blood correlated significantly with lymph node involvement by the
      gastric carcinoma, but not with serosa invasion or more advanced stage of
      neoplasia.

PMID- 18060279
TI  - Association between Helicobacter pylori concentration and the combining frequency
      of histopathological findings in gastric biopsies specimens.
AB  - BACKGROUND: Helicobacter pylori is the most prevalent infectious agent worldwide.
      About 90% of patients with chronic gastritis are infected with this bacterium.
      Some studies have shown a association between the H. pylori concentration and the
      scores of gastritis activity and severity. AIM: To evaluate the association
      between H. pylori concentration and the combining frequency of findings on
      histopathological examination. METHODS: Two hundred consecutive gastric
      endoscopic biopsies diagnosed as chronic gastritis were retrospectively
      investigated. The Warthin-Starry silver stain was used to study H. pylori and the
      following parameters were assessed (according to the Sydney system): 1.
      infiltration by polymorphonuclear cells in chorio and epithelium (activity)
      graded as mild, moderate and marked; 2. presence of lymphoid follicles; 3.
      presence of intestinal metaplasia; 4. presence of regenerative cell atypias,
      graded as mild, moderate and marked; and 5. H. pylori concentration on the mucous
      covering the foveolar epithelium. RESULTS: The most frequent association was
      chronic gastritis and activity, regardless of H. pylori concentration. The
      association of five histopathological findings in the same biopsy has not
      occurred in the cases of higher concentration of H. pylori. CONCLUSION: Our study
      has not revealed any association between H. pylori concentration and an
      increasing in the number of histopathological findings found in the gastric
      mucosa. Since referring to its presence is much more important than to its
      concentration.

PMID- 18060280
TI  - Randomized clinical trial comparing sodium picosulfate with mannitol on the
      preparation FOR colonoscopy in hospitalized patients.
AB  - BACKGROUND: The cleansing of the colon for a colonoscopy exam must be complete so
      as to allow the visualization and inspection of the intestinal lumen. The ideal
      cleansing agent should be easily administered, have a low cost, and minimum
      collateral effects. Sodium picosulfate together with the magnesium citrate is a
      cathartic stimulant and mannitol is an osmotic laxative, both usually used for
      this purpose. AIMS: Assess the colon cleanliness comparing the use of mannitol
      and sodium picosulfate as well as evaluate the level of patient satisfaction, the
      presence of foam, pain, and abdominal distension in hospitalized patients
      undergoing colonoscopy. METHODS: A prospective, randomized, single-blind study
      with 80 patients that compared two groups: mannitol (40) and sodium picosulfate
      (40). Both groups received the same dietary orientation. The study was approved
      by the hospital's Ethics and Research Committee. The endoscopist was blind to the
      type of preparation. Outcomes evaluated: level of the colons cleanliness,
      patients satisfaction, the presence of foam, abdominal pain and distension, and
      the duration of the exam. The data was analyzed by means of the chi-squared test
      for proportions and Mann-Whitney for independent samples. RESULTS: There were no
      statistically significant differences between the groups in relation to the level
      of the colon's cleanliness, patients satisfaction, the presence of foam,
      abdominal pain, and the duration of the exam. Fifteen percent of the exams of the
      mannitol group were interrupted while from the sodium picosulfate group it was
      5%. The presence of foam was similar for both groups. The average duration for
      carrying out the exam was 28.44 minutes for the mannitol group and 35.59 minutes
      for the sodium picosulfate group. Abdominal distension was more frequent in the
      mannitol group. If they would have to do the same exam, the answer was that 80%
      said yes from the mannitol group and 92.5% from the sodium picosulfate group.
      CONCLUSION: The quality of the colon preparation, foam formation, exam duration,
      and the collateral effects (nauseas, vomiting, and abdominal pain) were similar
      in both kinds of preparations. Abdominal distension was greater in the mannitol
      group. Both methods of preparation were well accepted by the hospitalized
      patients.

PMID- 18060282
TI  - [Clinical profile of Santa Catarina members of Brazilian Celiac Association].
AB  - BACKGROUND: Celiac disease is an enteropathy induced by gluten in genetically
      predisposed individuals. AIM: To establish the demographic and clinical
      characteristics of this disease in Santa Catarina State, Brazil. METHODS: A
      descriptive transversal study was performed involving members of a regional
      celiac association, to whom a questionnaire focusing various aspects of the
      disease was sent. RESULTS: From a total of 506 members, 145 (28.7%) were enrolled
      in the study--all of them biopsy-proven celiacs. Their mean age was 30.8 years
      (range, 3.3-82.5 years). Female to male rate was 2.1:1. The mean age at diagnosis
      was 16 years for men and 26.7 years for women. Most frequently reported symptoms
      were: abdominal distention (71.8%), abdominal pain (71%) and diarrhea (65.5%).
      Anemia, aphthous ulcers and constipation were more related by women, while
      diarrhea and low weight were more frequent in men. Only 42.1% of the participants
      had been submitted to biopsies compatible with a correct investigation of the
      disease (44.2 % had been submitted to biopsy only after gluten exclusion of the
      diet and 11.7% did not mentioned whether they were in a gluten-free diet when
      biopsied). Only 61.4% had been submitted to serological tests for diagnostic or
      dietary control purposes. Associated diseases were related by 65% of the
      individuals, of which the most common was lactose intolerance (33%). Vitaminic or
      mineral supplementation was indicated to 45% and only 32.5% have had bone mineral
      density measured. Of these, 59% had altered results. CONCLUSIONS: The results
      suggest a tendency of diagnosis of celiac disease in older ages, specially among
      women. This may indicate the necessity of improving public and medical knowledge
      in Santa Catarina concerning the diagnosis and treatment of this disease.

PMID- 18060281
TI  - Endoscopic mucosal resection of early gastric cancer: initial experience with two
      technical variants.
AB  - BACKGROUND: When performed in carefully selected cases, the endoscopic treatment
      of early gastric cancer yields results which are comparable to the conventional
      surgical treatment, but with lower morbidity and mortality and better quality of
      life. Several technical options to perform endoscopic mucosal resection have been
      described and there is a large amount of accumulated experience with this
      procedure in eastern countries. In western countries, particularly in Brazil,
      technical limitations associated with the small number of cases of early gastric
      cancer reflect the little experience with this therapeutic mode. AIM: This study
      was carried out in order to assess the indications, pathological results and
      morbidity of a series of endoscopic mucosal resections using two technical
      variants in addition to investigating the safety and feasibility of the method.
      METHODS: Individuals with well-differentiated early gastric adenocarcinomas with
      up to 30 mm in diameter without scar or ulcer underwent endoscopic treatment. Two
      variants of the strip biopsy technique were used. The pathological study assessed
      the depth of the vertical invasion, lateral and basal margins as well as angio
      lymphatic invasion. RESULTS: Thirteen tumors in 12 patients were resected between
      June 2002 and August 2005. The most common macroscopic types were IIa and IIa +
      IIc. Tumor size ranged from 10 to 30 mm (mean = 16.5 mm). En bloc resection was
      carried out in nine patients. Angio-lymphatic invasion was not observed; however,
      submucosal invasion was found in two cases. In four cases, the lateral margin was
      involved. Perforation occurred in two patients who then received conservative
      treatment. CONCLUSION: The relatively small series presented here suggests that
      the method is safe and feasible. Appropriate patient selection is the most
      important criteria. Long follow-up is required after treatment due to the risk of
      relapse.

PMID- 18060283
TI  - The presence of Helicobacter pylori in postmenopausal women is not a factor to
      the decrease of bone mineral density.
AB  - BACKGROUND: Osteoporosis affects approximately 30% of postmenopausal women.
      Gastrectomy, pernicious anemia, and more recently Helicobacter pylori infection,
      have all been implicated in the pathogenesis of osteoporosis. A reduced parietal
      cell mass is a common feature in these conditions. AIM: To study a possible
      relationship between chronic gastritis, parietal cell density of the oxyntic
      mucosa and bone mineral density in postmenopausal women, as chronic gastritis,
      Helicobacter pylori infection and osteoporosis are frequently observed in the
      elderly. METHODS: Fifty postmenopausal women (61.7 +/- 7 years) were submitted to
      gastroduodenal endoscopy and bone densitometry by dual energy X-ray
      absorptiometry. Glandular atrophy was evaluated objectively by the determination
      of parietal cell density. Helicobacter pylori infection was evaluated by
      histology, urease test and breath test with 13C. RESULTS: Thirty-two patients
      (64%) presented chronic multifocal gastritis, and 20 of them (40%) showed signs
      of gastric mucosa atrophy. Lumbar spine osteoporosis was found in 18 patients
      (36%). The parietal cell density in patients with and without osteoporosis was
      948 +/- 188 and 804 +/- 203 cells/mm(2), respectively. Ten osteoporotic patients
      (55%) and 24 non-osteoporotic patients (75%) were infected by Helicobacter
      pylori. CONCLUSION: Postmenopausal women with osteoporosis presented a well
      preserved parietal cell density in comparison with their counterparts without
      osteoporosis. Helicobacter pylori infection was not different between the two
      groups. We concluded that neither atrophic chronic gastritis nor Helicobacter
      pylori seem to be a reliable risk factor to osteoporosis in postmenopausal women.

PMID- 18060284
TI  - Perioperative fluorocholangiography with routine indication versus selective
      indication in laparoscopic cholecystectomy.
AB  - BACKGROUND: The use of routine or selective peroperatory cholangiography in
      cholecystectomy is a matter of controversy in literature. AIM: To compare the
      efficacy of selective or routine fluorocholangiography in diagnostic of common
      bile duct stone in patients underwent to laparoscopic cholecystectomy based on
      selective indication criteria. METHOD: Two hundred and fifty four patients with
      cholelithiasis were prospectively studied. The patients were divided in two
      groups: to the first 127 patients perioperative fluorocholangiography was
      indicated as routine (group 1), and to the other 127 patients perioperative
      fluorocholangiography indication followed clinical criteria (jaundice, choluria,
      fecal acholia and history of pancreatitis), laboratory criteria (increase in
      seric alkaline phosphatase, bilirubins, amylase) or ultra-sonographyc criteria
      (less than 6 mm diameter calculi, common bile duct stone, common bile duct
      diameter more than 6 mm). A comparative assessment of the difference in common
      bile duct stone diagnosis, fluorocholangiography success index and reliability of
      the selective criteria of indication for perioperative fluorocholangiography was
      compared between the two groups. RESULTS: Perioperative fluorocholangiography was
      successfully performed in 102 of the 127 patients from group 1 (a rate of 80.3%),
      and in 59 of the 71 patients from group 2 (a rate of 83.1%). In the 102 patients
      of group 1 who underwent perioperative fluorocholangiography, 11 (10.8%)
      presented common bile duct stone, 4 (3.9%) presented common bile duct dilatation,
      and 1 (1%) had a false-positive image. In the 59 patients from group 2, 7 (11.7%)
      presented common bile duct stone and one (1.7%) presented a common bile duct
      diatation. In another situation, when application of selective indication
      criteria to perioperative fluorocholangiography was simulated in group 1
      patients, we observed that only in one patient with common bile duct stone the
      diagnostic would not have been made. Fluorocholangiography selective indication
      criteria presented sensitivity of 90.9% and specificity of 46.2%. The main causes
      of fluorocholangiography failure were biliary pedicle inflammation and cystic
      duct size and caliber variations. CONCLUSION: There was not a significant
      difference in common bile duct stone diagnostic through perioperative
      fluorocholangiography between the groups of patients with selective and routine
      indication, validating the examination selective indication criteria, with a
      sensitivity of 90.9%, despite the specificity of 46.2%--43 patients were selected
      to the flourocholangiography and common bile duct stone was not diagnosed.

PMID- 18060285
TI  - [Protective effects of an inhibitor of glycoprotein IIb/IIIa in the hepatic and
      pulmonary disturbances secondary to ischemia and reperfusion injury of rat's
      liver].
AB  - BACKGROUND Hepatic ischemia-reperfusion injury is responsible for a considerable
      morbidity and mortality. AIM: To evaluate the effect of a platelet glycoprotein
      IIb/IIIa receptor inhibitor (tirofiban) on hepatic and pulmonary disturbances
      associated with hepatic ischemia-reperfusion injury. METHODS: Twenty-three Wistar
      rats divided in three groups: rats sham-operated (n = 6), rats submitted to
      ischemia-reperfusion that received saline solution (n = 8), and rats submitted to
      ischemia-reperfusion treated with 0.7 mg/kg of tirofiban (n = 9). Serum
      aminotransferases (AST and ALT) were also determined, and the study of hepatic
      tissue histology was carried out. The evaluation of the pulmonary disturbances
      was done using the Evans blue test and the tissular determination of
      myeloperoxidase. Hepatic mitochondrial oxidation and phosphorylation were also
      measured. RESULTS: There was an increase in the state 3 respiration, ADP/O ratio
      and respiration control rate in the group treated with tirofiban. This group had
      also lower levels of aminotransferases and the histological findings were
      significantly less intense. Pulmonary evaluation demonstrated decrease of the
      Evans blue test in the tirofiban group and an increase of its tissular
      determination of myeloperoxidase. CONCLUSION: The inhibition of glycoprotein
      IIb/IIIa receptor with tirofiban protected the hepatic disturbances and prevented
      the increase of pulmonary vascular permeability secondary to the ischemia
      reperfusion injury of the liver.

PMID- 18060286
TI  - [Visual and olfactory factors interaction in resource-location by the blowfly,
      Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae), in natural
      conditions].
AB  - The interaction between olfactory and visual cues in the landing responses of
      Chrysomya megacephala (Fabricius) was analyzed in a natural environment (grass)
      using three plain cardboard circles with the colors white, black and other being
      the own grass (control) with 30 cm in diameter. The circles were divided in four
      quadrants and five sectors using as bait 80 mg of carcass of fish and minced
      flesh put in the center. To check the interaction between visual and olfactory
      factors, we analyzed the relation among the direction of wind and the sectors,
      the quadrants and the color of circle where C. megacephala adults landed. In the
      presence of the black and white circles, flies landed closer to the central
      release point of the bait when the wind was present compared with the other
      control circle. The results show that while odor cues may enhance the induction
      of landing by C. megacephala, visual cues are important when selecting a final
      landing site. Improved understanding of this interaction may allow the
      development of more effective traps or targets, enhancing the control efficiency
      of these control devices.

PMID- 18060287
TI  - [Arthropod community associated with the canopy of Attalea phalerata Mart.
      (Arecaceae) during the flood period of the Pantanal of Pocone, Mato Grosso,
      Brazil].
AB  - Six trees of the palm species Attalea phalerata Mart. were sampled during high
      water (aquatic phase) of the Pantanal of Mato Grosso (February 2001), by canopy
      fogging. The composition, structure, and biomass of the arthropod community
      associated with their canopies were analysed, as well as the influence the flood
      pulse renders on it. Each tree was fogged once, followed by three consecutive
      collections. A total of 63,657 arthropods (643.0 +/-; 259.87 ind./m(2)) were
      collected, representing 25 orders in the classes Insecta, Arachnida, Diplopoda
      and Crustacea. The dominant groups were Acari (40.0%; 257.2 +/- 116.50
      ind./m(2)), Coleoptera (12.0%; 77.5 +/- 64.93 ind./m(2)), Psocoptera (9.2%; 59.0
      +/- 38.00 ind./m(2)), Diptera (8.4%; 54.1 +/- 18.72 ind./m(2)), Collembola (8.3%;
      53.4 +/- 26.24 ind./m(2)) and Hymenoptera (7.9%; 50.6 +/- 21.40 ind./m(2)), the
      latter mostly represented by Formicidae (49.2%). Arthropod biomass amounted to
      8.86 g dry weight and 0.18 mg/m(2). Coleoptera, Blattodea, Orthoptera, Araneae
      and Hymenoptera were the most representative taxa. The hydrological regime (flood
      pulse), as well as seasonality, appear to strongly affect the composition and
      structure of this canopy community.

PMID- 18060288
TI  - [Foraging behavior of Xylocopa (Neoxylocopa) cearensis Ducke (Hymenoptera:
      Apidae, Xylocopini) in a population of Cuphea brachiata Koehne (Lythraceae)].
AB  - An analysis of the foraging behavior of the bee Xylocopa (Neoxylocopa) cearensis
      Ducke among shrubs of Cuphea brachiata Koehne (Lythraceae), a key component in
      the Abaete coastal sand dunes, Salvador, BA, Brazil, suggests that this bee is
      very important for the maintenance of the plant population, performing the
      pollination. This dispersal, however, is spatially restricted, so the populations
      in the area are likely to be highly structured genetically.

PMID- 18060289
TI  - [Thermal requirements of Galleria mellonella L. (Lepidoptera: Pyralidae) immature
      stages].
AB  - The rearing of Galleria mellonella L. in laboratory is important for
      multiplication of entomopathogenic nematodes, mandatory for biological control
      studies. The objective of this study was to evaluate the effect of three thermal
      profiles on development stages of this insect, allowing synchronization of cycle
      production. Two distinct rearing phases were done: firstly, using nucleous of
      incubation for development of eggs and, secondly, using circular-aluminum
      manifolds for development of larvae and pupae. The time necessary for development
      of the immature stages decreased with higher temperatures. Incubation periods
      lasted 13.4 days at 22 degrees C, 8.3 at 27 degrees C and 6.8 days at 32 degrees
      C, while periods for larvae development lasted 40.4, 27.2, and 23.4 days,
      respectively, for the same temperatures. Development to pupal stage was observed
      18.2, 15.0, and 12.2 days, respectively, for the same temperatures. Larval
      survival was higher at 32 degrees C, however embryonic stages and pupae survival
      were higher at 27 degrees C. and 22 degrees C, respectively. The threshold
      temperature was 11.209167 degrees C for the embryonic development stage, 7.695869
      degrees C for larval stage, and 1.943050 degrees C for pupal stage of G.
      mellonella. Thermal constants were 138.380533 DG (degree day) for egg, 554.968830
      DG for larvae, and 369.054080 DG for pupae.

PMID- 18060290
TI  - [Evidences of Moran effect in the population synchrony: a demonstration in
      experimental microcosm].
AB  - Three main causes to population synchrony are proposed: exogenous factors,
      dispersal and inter-specific interactions. This paper had as main goal to test
      the influence of the exogenous factors in the synchrony in spatially isolated
      (i.e., no dispersal) populations of Sitophilus zeamais (Mots.) (Coleoptera:
      Curculionidae), in microcosms with different environmental conditions (humidity,
      temperature and light intensity). Twelve populations of 20 individuals each, were
      randomly assigned between two treatment conditions: with or without light.
      Population size and environmental factors (temperature and relative humidity)
      were weekly assessed for seven months. Temporal trend in populations increase was
      eliminated adjusting autoregressive models. Population synchrony, detected by
      means of Pearson's and Spearman's correlation coefficients, was higher within
      than between treatments, although the populations kept without lamp were more
      synchronized than populations with lamp. Besides demonstrating the influence of
      environment on population fluctuations, these results suggest that metabolism and
      intra-specific interactions are important factors in population dynamic.
      Organisms exposed to unsuitable environmental conditions may have abnormal
      metabolic rates, which negatively influences the population grow. Thus, small
      populations are more likely to suffer from demographic stochasticity, decreasing
      the probability of the synchrony among populations. On the other hand, in more
      suitable environments, individuals are expected to have normal metabolic
      functions, and so, to achieve higher rates of population grow. In this case, the
      demographic stochasticity has smaller influence, leading populations without lamp
      to fluctuate synchronously.

PMID- 18060291
TI  - [Influence of mulberry cultivars Morus spp. on the production and quality of
      silkworm Bombyx mori L. (Lepidoptera: Bombycidae) cocoons].
AB  - The success of sericiculture greatly depends on the availability of mulberry
      cultivars with agronomic characteristics that maximize the production and quality
      of silkworm, Bombyx mori L., cocoons. The effect of the cultivars Miura
      (standard) and Korin, and the hybrids SM 14, SM 63, SK 1, SK 4 and FM 86 was
      evaluated on silkworm development, and on cocoon production and quality, at the
      Instituto Agronomico do Parana, IAPAR, in Londrina, PR, Brazil (23 +/- 3 degrees
      C; 61 +/- 8% RH). The experiment was arranged in a randomized block design with
      four replicates. Larvae feeding either on 'SK 4' or on 'Korin' showed a higher
      weight compared to that of larvae feeding on 'Miura'. Cocoon weight (both sexes)
      and pupae weight (male) obtained with larvae fed on SK 4 were higher compared
      with that of insects that fed on Miura; there was no difference among the
      remaining treatments. Silk net weight was independent of the cultivar used.
      Cocoon shell weight was similar amongst insects raised on 'Miura' and on the
      other mulberry materials. The percentage of cocoon spinning was higher than 90%
      in all treatments, with the spinning concentrating in the first two days. The
      proportion of first grade cocoons varied from 80% (SK4) to 90%. The results
      obtained with the studied cultivars were either similar or superior to that of
      the standard cultivar Miura with emphasis to 'SK 4', thus showing the potential
      use of these cultivars in sericulture in the state of Parana.

PMID- 18060292
TI  - Utilization of floral resources by bees of the genus Frieseomelitta von Ihering
      (Hymenoptera: Apidae).
AB  - The present study intended to verify which factors (phylogenetic relationship or
      local ecological conditions) would determine how Frieseomelitta bees use floral
      resources. The data obtained in the literature on biocenotic studies of Apoidea
      visiting flowers in Brazil were analyzed, with identification and quantification
      of floral resources used by Frieseomelitta species in different areas. The
      phenogram of similarity on use of resources among Frieseomelitta species was
      compared to the phylogenetic hypothesis proposed for the group. Among the eight
      Frieseomelitta species registered in 19 studies, F. doederleini (Friese), F.
      francoi (Moure), F. languida Moure, F. varia (Lepeletier) e Frieseomelitta sp.
      nov., were collected using resources from 36 plant families. F. doederleini, F.
      languida e F. varia centralized their activity in Caesalpiniaceae, Malpighiaceae
      e Anacardiaceae. The similarities and disparities found among areas and
      Frieseomelitta species reflected the similarities and differences of the
      vegetation composition in each area. Frieseomelitta bees presented a forage
      pattern similar to that one presented by other highly social bees, visiting
      flowers of many plant species, but concentrating their activities in few plant
      species. Despite the low phylogenetic relationship between F. languida and F.
      doederleini, they showed a high similarity on the use of floral resource, while
      F. varia e F. languida, species with high phylogenetic relationship, showed low
      similarity in the use of resource. Although the data obtained are not conclusive,
      it indicates that phylogenetic restrictions do not influence the pattern of use
      of floral resource by Frieseomelitta bees.

PMID- 18060293
TI  - Diversity of social wasps (Hymenoptera: Vespidae) in Cerrado fragments of
      Uberlandia, Minas Gerais State, Brazil.
AB  - Studies of species survey are important to know the available natural resources
      and to get useful information about the ecological characteristics of a specific
      area. There are not studies, on this issue, related to social wasps, in the
      Triangulo Mineiro region. The present study describes the diversity of species
      found in fragments of the cerrado region in Uberlandia, MG, and their temporal
      distribution. The field study was conducted from October 2003 to September 2004,
      and 43 samplings were carried out using active searching (24) and point sampling
      (19) methodologies. Twenty-nine species were found in 10 genera, Polybia and
      Polistes corresponding to 51.5% of the total listing. Mischocyttarus cerberus
      styx Richards represented 26.5% of the total individuals recorded by active
      searching and Agelaia pallipes (Olivier) corresponded to 57.6% by point sampling.
      Two species had their first record for the state of Minas Gerais: Polybia striata
      (Fabricius) and M. cerberus styx. The studied fragments presented a high level of
      diversity (H' = 0.66 to 1.16), a large number of rare species and a few common
      species. To collect the more common species the point sampling method was
      satisfactory while active searching was better to collect the rarer species. The
      active searching methodology was more efficient than point sampling, however some
      species could only be collected by point sampling. These factors showed that in
      order to carry out a wasp survey, a combination of different collection
      methodologies seems to be more appropriate.

PMID- 18060294
TI  - Biomass and population structure of Constrictotermes cyphergaster (Silvestri)
      (Isoptera: termitidae) in the dry forest of caatinga, northeastern Brazil.
AB  - Biomass and population structure of Constrictotermes cyphergaster (Silvestri)
      were studied in an area of dry forest of caatinga in the State of Paraiba,
      northeastern Brazil. Twelve nests of different sizes were randomly collected,
      being six during the dry season (November 2004 and 2005) and six during the wet
      season (March 2004). Soldier and worker populations varied between 4880 and
      118800 individuals per nest. The ratio between soldiers and workers did not
      significantly vary between seasons. Biomass (measured as fresh weight) of
      individuals varied between 13.9 and 408.8 g per nest, and soldiers and workers
      had significantly greater biomass during the wet season. The estimated density of
      nests of C. cyphergaster was 59.0 +/- 22.53 active nests/ha. Quantitative data of
      the study colonies and data on the nest abundance showed that C. cyphergaster
      encompassed some 278.2 individuals/m(2), with approximately 0.9 g (fresh
      weight)/m(2). These data suggest that C. cyphergaster is an important consumer of
      vegetal matter and, therefore, an important species affecting the nutrient
      cycling and energy flow in the caatinga vegetation.

PMID- 18060295
TI  - [The neotropical genus Brachymyrmex Mayr (Hymenoptera: Formicidae) in Argentina.
      III. redescription of species: B. aphidicola Forel, B. australis Forel B.
      constrictus Santschi].
AB  - Three species of the genus Brachymyrmex: B. aphidicola Forel, (n.stat.); B.
      australis Forel y B. constrictus Santschi are redescribed hereafter. Descriptions
      and drawings of main morphological characters of gynes, males and workers are
      given. New characters are used to differentiate species, mainly based on male
      head morphology and genitalia. New Argentine localities are added to the known
      distribution.

PMID- 18060296
TI  - Histochemical and ultrastructural evidence of lipid secretion by the silk gland
      of the sugarcane borer Diatraea saccharalis (Fabricius) (Lepidoptera: Crambidae).
AB  - The silk gland in Lepidoptera larvae is responsible for the silk production used
      for shelter or cocoon construction. The secretion of fibroin and sericin by the
      different silk gland regions are well established. There are few attempts to
      detect lipid components in the insect silk secretion, although the presence of
      such element may contribute to the resistance of the shelter to wet environment.
      This study characterizes the glandular region and detects the presence of lipid
      components in the secretion of the silk gland of Diatraea saccharalis(Fabricius).
      The silk gland was submitted to histochemical procedure for lipid detection or
      conventionally prepared for ultrastructural analyses. Lipid droplets were
      histochemically detected in both the apical cytoplasm of cell of the anterior
      region and in the lumen among the microvilli. Ultrastructural analyses of the
      anterior region showed lipid material, visualized as myelin-like structures
      within the vesicular Golgi complex and in the apical secretory globules, mixed up
      with the sericin; similar material was observed into the lumen, adjacent to the
      microvilli. Lipids were not detected in the cells neither in the lumen of the
      posterior region. Our results suggest that the silk produced by D. saccharalis
      has a minor lipid content that is secreted by the anterior region together with
      the sericin.

PMID- 18060297
TI  - Molecular identification of species of the genus Euglossa Latreille (Hymenoptera:
      Apidae, Euglossini).
AB  - Euglossine bees interact with more than 60 plant families of the Neotropical
      region. The richness and abundance of these bees have been intensively studied in
      different ecosystems using the methodology of capturing males with chemical
      baits. Females are poorly known for most of the species and morphological
      characters for their taxonomic classification have not yet been described. The
      purpose of this study was to use allozymes and restriction patterns of the
      mitochondrial regions 16S and Cyt b to identify species of Euglossa Latreille.
      Bees were collected while visiting Thevetia peruviana (Apocynaceae) flowers in
      five cities of the state of Sao Paulo, Brazil. Three Euglossa species were
      identified among the 305 individuals collected. Euglossa cordata (L.) was the
      only species found in all cities, while E. securigera Dressler and E. townsendi
      Cockerell were restricted to two and one cities respectively. EST-3 was a
      diagnostic marker, whereas ICD, MDH, ME and PGM were informative for species
      identification when used in combination. Restriction by VspI of the amplified 16S
      fragment differentiated the three species and showed intraspecific polymorphism
      for E. cordata and E. securigera. The Cyt b region showed distinctive patterns
      for E. townsendi but it was not possible to differentiate the other two species.
      Our results describe potentially useful genetic markers for the identification of
      Euglossa spp. at the species and group level.

PMID- 18060298
TI  - Morphology and distribution of antennal sensilla of Gryon gallardoi (Brethes)
      (Hymenoptera: Scelionidae) females.
AB  - With the aid of scanning electron microscopy, the external morphology and
      distribution of the antennal sensilla were described for females of Gryon
      gallardoi (Brethes), an egg-parasitoid of coreids. The geniculated and clavated
      antennae are composed of 12 antennomeres. Along the flagelum we registered dorsal
      glands and seven types of sensilla: papillary, chaetica of two sizes--long and
      short types, styloconic grooved-peg, sickle-shaped and trichodea with numerical
      and spatial variation among the flagellomeres. Functional aspects of the sensilla
      are discussed in the context of G. gallardoi antennal drumming behavior. Thus,
      the determination and the description pattern of antennal sensilla in G.
      gallardoi, in the present study, is an advance regarding the elucidation of the
      mechanisms involved in the host selection behavior of this species.

PMID- 18060299
TI  - A revision of the neotropical genus Anahi Martinez (Coleoptera: Scarabaeidae:
      Melolonthinae) with the description of two new species.
AB  - The southern Neotropical genus Anahi Martinez is comprehensively revised and now
      includes three species: A. dentata Ocampo Ruiz-Manzanos new species, A.
      guaraniticus Martinez, and A. oblivia Ocampo Ruiz-Manzanos new species. The new
      species extend the distribution of the genus from Paraguay and Bolivia to
      Argentina. A. guaraniticus is redescribed and the characters that define the
      genus are extended to include A. dentata and A. oblivia. Descriptions, diagnosis
      illustrations, distribution maps and a key to all species of the genus are
      provided. The biogeography of the genus and its systematic placement within
      Melolonthinae are here discussed.

PMID- 18060300
TI  - [Association of bioassays and molecular characterization to select new Bacillus
      thuringiensis isolates effective against Spodoptera frugiperda (J. E. Smith)
      (Lepidoptera: Noctuidae)].
AB  - The fall armyworm, Spodoptera frugiperda (J. E. Smith), is one of the main corn
      pests and Bacillus thuringiensis is important in its control because of its
      entomopathogenic property. The objective of this study was the molecular
      characterization of B. thuringiensis isolates for cry1 locus presence and the
      assessment of the efficiency of these isolates in controlling S. frugiperda
      caterpillars. Gral-cry1 was used in the PCR analyses to confirm the presence of
      the cry1 locus in 15 isolates. A 3 x 10(8) spore/ml suspension bathed the diet
      used to feed 30 caterpillars per isolate, with three replications. The cry1 locus
      type genes of the different isolates were identified for five gene subclasses;
      linear regression analyses were carried out to ascertain possible associations
      between the presence of an individual cry1 locus gene and high levels of
      toxicity. All the DNAs amplified with Gral-cry1 presented an amplification
      product with the expected size. Regarding the levels of insecticide efficiency
      against the cob worm, 41 isolates presented 100% mortality and 16 presented an
      index between 70% and 90%. The cry1Ab gene was present in 80 isolates, cryb in 69
      isolates, cry1Ac in all the isolates and cryv and cry1E in 93 and 27 isolates,
      respectively. The values regarding the individual effect of each gene on
      caterpillar mortality were significant at 1% probability for the cry1Ac and cry1E
      genes.

PMID- 18060301
TI  - Structure and composition of the assemblage of parasitoids associated to
      Phyllocnistis citrella Pupae Stainton (Lepidoptera: Gracillariidae) in citrus
      orchards in Southern Brazil.
AB  - The structure and composition of the assemblage of pupal parasitoids of
      Phyllocnistis citrella Stainton, the citrus leafminer, were studied in two citrus
      orchards (Citrus deliciosa Tenore cv. Montenegrina and Citrus sinensis (L.)
      Osbeck x Citrus reticulata Blanco hybrid Murcott), in Montenegro County (29
      degrees 68'S and 51 degrees 46'W), southern Brazil. At fortnightly samplings,
      from July 2001 to June 2003, all the new shoots from 24 randomly selected trees
      were inspected. The species richness reached five native species in the Murcott
      orchard, and six in Montenegrina. In Murcott, the presence of Ageniaspis
      citricola (Hymenoptera: Encyrtidae), an exotic species, was detected in the first
      year of sampling, probably migrating from the nearby areas where it had been
      released for the miner control. In Montenegrina, its presence was only registered
      in the second year. A. citricola in both areas was dominant and changed the
      community structure of parasitoid complex of P. citrella in both orchards.

PMID- 18060302
TI  - [Effects of nitrogen fertilization in cotton crop on Aphis gossypii Glover
      (Hemiptera: Aphididae) biology].
AB  - The cotton aphid, Aphis gossypii Glove, is one of the pests of cotton crop and
      its relation with the host seem to depend on the amount of nitrogen available to
      the plant. The biology of A. gossypii using different cotton nitrogen fertility
      regimes was studied under greenhouse conditions, in Dourados, MS. A completely
      randomized design with nine replications in a factorial scheme (2x4x2)+1 was
      used. Two nitrogen sources (sulphate of ammonium and urea), four doses of
      nitrogen (50, 100, 150 and 200 kg ha-1), two different times of nitrogen
      application and one additional treatment without nitrogen were taken as factors.
      The nymphal phases, the pre-reproductive, reproductive and pos-reproductive
      periods, longevity, the life cycle and fecundity of the cotton aphid were
      evaluated. The doses of nitrogen influenced the cotton aphid biology in both
      sources and times of application, favoring its development and fecundity.

PMID- 18060303
TI  - Feeding and oviposition preference of Phyllophaga cuyabana (Moser) (Coleoptera:
      Melolonthidae) on several crops.
AB  - Laboratory and greenhouse experiments were carried out to study food and
      oviposition preference by Phyllophaga cuyabana (Moser) on different plant species
      as Cajanus cajan L. (pigeon pea), Crotalaria juncea L. (sun hemp), Crotalaria
      spectabilis Roth (showy crotalaria), Crotalaria ochroleuca G. Don (slenderleaf
      rattlebox), Glycine max [L.] Merrill (soybean), Gossypium hirsutum L. (cotton),
      Helianthus annuus L. (sunflower), Stizolobium aterrimum [Mucuna aterrima] Piper
      Tracey (velvetbean) and Zea mays L. (mayze). In no-choice experiments, the number
      of eggs layed in sunflower, C. juncea and soybean was larger compared to cotton.
      Despite the fact that the adults did not discriminate among plants, in dual
      choice test, the proportion of eggs layed and leaf consumption by P. cuyabana
      adults in soybean were significantly higher than in C. spectabilis. The larval
      distribution in the soil was at random in multiple-choice, without any trend of
      preference, but in dual-choice, when soybean was the control, larvae always
      preferred to feed on its roots. P. cuyabana adults had preference for more
      suitable hosts and that could stand their offspring survival. This behaviour can
      be usefully exploited in an integrated management program for this pest.

PMID- 18060304
TI  - [Entomofauna associated to horticultural crops under organic and conventional
      practices in Cordoba, Argentina].
AB  - Farming practices and the addition of chemical synthetic substances in
      conventional agroecosystems are detrimental mainly to natural enemies of
      phytophagous insects, diminishing the natural regulation of pest insects. On the
      other hand, in organic agriculture, biological processes and care of the
      environment are favoured, hence an increase in insect biodiversity is predicted
      in this type of systems. In this work, abundance, richness of insects and
      proportion of functional groups were compared through a single quantitative
      sampling of insects in horticultural crop fields, three under organic and three
      under conventional management practices. Insect species richness, total and for
      guilds (phytophagous and entomophagous insects) were significantly higher in
      organic orchards, and also was the abundance of entomophagous insects. Richness
      and abundance of all insect orders (with exception of Homoptera abundance), were
      higher in orchards under organic management, being significative the differences
      for richness of Coleoptera and richness and abundance of Hymenoptera. Similar
      tendencies were observed in data obtained through sweep net in weeds. These
      results suggest that organic practices increase the diversity of species,
      particularly that of natural enemies.

PMID- 18060305
TI  - Mite diversity on plants of different families found in the Brazilian Atlantic
      Forest.
AB  - This work reports the occurrence of mites predominantly predatory, phytophagous
      and with varied feeding habits on plants of the Atlantic Forest vegetation type
      of the State of Sao Paulo. The objective was to estimate the possible role of the
      Atlantic Forest vegetation as reservoir of these groups of mites which are also
      found on plants of agricultural importance. Samples were taken from 187 plant
      species belonging to 73 families in three vegetation types of the Atlantic Forest
      from February of 2001 to October of 2002. A total of 2,887 mites belonging to 163
      morpho-species of 16 families were collected. Mite diversity was high, especially
      of predatory mites; these corresponded to 1,562 specimens of 92 morpho-species.
      Within this group, Phytoseiidae comprised 71% of the specimens and 62% of the
      morpho-species. Phytophagous mites comprised 836 specimens of 36 morpho-species.
      Within this group, Tenuipalpidae comprised the larger proportion of specimens
      (61%) whereas Tetranychidae corresponded to the larger proportion of morpho
      species (64%). Mites with varied feeding habits corresponded to 491 specimens of
      36 morpho-species. In this group, the larger proportion of specimens (52%)
      consisted of Ascidae and the larger proportion of morpho-species (42%) consisted
      of Tydeinae (family Tydeidae). High abundance and high morpho-species richness of
      mites of predominantly predatory, phytophagous and variable feeding habits were
      observed on 17, five and nine plant species, respectively. The results obtained
      suggest the importance of plants of the studied vegetation as reservoirs of
      predatory mites.

PMID- 18060306
TI  - [Spatial distribution of phytophagous mites (Acari: Tetranychidae) on strawberry
      plants].
AB  - Many phytophagous mites can attack strawberry plants, Fragaria x ananassa, among
      them the southern red mite, Oligonychus ilicis McGregor, and the two-spotted
      spider mite, Tetranychus urticae Koch. They are found together feeding on the
      same plant on the upper and underside of the leaves, respectively. Here we
      studied the choice for feeding sites of O. ilicis and T. urticae on strawberry
      plants. The first hypothesis tested whether the feeding site choice would be
      related to the fitness of the species. The second hypothesis dealt whether the
      feeding site would be determined by the presence of a heterospecific mite. We
      evaluated the preference, biology and reproductive success of O. ilicis and T.
      urticae on the under and upper side surface of strawberry leaves infested or not
      by the heterospecific. O. ilicis preferred to stay on the upper side surface
      while T. urticae preferred the underside. The preference for the leaf surface
      correlated with the reproductive success of the species (measured by the
      intrinsic growth rate). The choice pattern of feeding sites did not alter when
      the choice test was applied using sites previously infested by heterospecific.
      Although O. ilicis and T. urticae, apparently, do not interact directly for
      feeding sites, there is a chance that the first species induces defenses in
      strawberry plant enabling to reduce the fitness of the second species. The
      possibility of those species stay together on strawberry plant increases the
      damage capacity to the culture.

PMID- 18060307
TI  - [Seasonality and diurnal activity of Tabanidae (Diptera: Insecta) of canopy in
      the Adolpho Ducke Forested Reserve, Manaus, Amazonas State, Brazil].
AB  - The seasonality and diurnal flight activity of tabanids from canopy was studied
      at Ducke Reserve, in the county of Manaus, Amazonas State, Brazil, using a
      suspended trap installed at 20 m above the soil, connected to the carbon dioxide
      gas cylinder. During one day, twice monthly collects of Tabanidae were taken from
      April 2000 to June 2001. The material was collected from the trap in intervals of
      2h and placed in plastic tubes. A total of 955 individuals, corresponding to
      thirty species were collected. Philipotabanus stigmaticalis (Krober) (37.9%) was
      caught all over the year and showed higher flight activity between 12:00 p.m. and
      4:00 p.m. Acanthocera marginalis Walker (16.3%) was more abundant in the less
      rainy months (July to November) with a higher activity period between 10:00 a.m.
      and 12:00 p.m. Acanthocera gorayebi Henriques Rafael (9.0%) was more abundant in
      July with more activity between 10:00 a.m. and 12:00 p.m. Dichelacera damicornis
      (Fabricius) (10.9%) was more abundant in the months of heavier rainfall (January,
      February and April) and showed higher diurnal activity between 10:00 a.m. and
      2:00 p.m. Diachlorus podagricus (Fabricius) (6.6%) was caught throughout the year
      except in February and showed higher activity between 10:00 a.m. and 14:00 p.m.
      The climatic factors when correlated to the tabanids richness just showed
      significant correlation with precipitation, while the specimens abundance was
      correlated to humidity and precipitation.

PMID- 18060309
TI  - [Occurrence of Ceratitis capitata Wied. (Diptera: Tephritidae) on papaya fruits
      in Minas Gerais State, Brazil].
AB  - The objective of this work was to register the infestation of C. capitata on
      papaya fruits in Minas Gerais State. Papaya fruits were collected, in a
      commercial orchard, in Jaiba, north of the State of Minas Gerais. C. capitata was
      the only specie collected (794 individuals). Doryctobracon areolatus (Szepligeti)
      was collected parasitizing C. capitata larvae/pupae. The level of infestation was
      of 7,7 pupae/kg of fruit or 1,4 pupae/fruit, in average. C. capitata is
      registered for the first time on papaya fruits in the State of Minas Gerais.

PMID- 18060308
TI  - [Morphological and histological study of eggs of six species of the Triatoma
      genus (Hemiptera: Reduviidae)].
AB  - The objective of this study was to analyze the morphological and histological
      characteristics of eggs from six triatomine species in order to obtain a generic
      and specific characterization of this group of Trypanosoma cruzi vectors and
      better understand their phylogenetic and taxonomic aspects. The eggs of the
      respective species came from the collection of the Laboratorio de Triatomineos e
      Culicideos da Faculdade de Saude Publica/USP, from the Insetario do Servico
      Especial de Saude de Araraquara - SESA and from the Triatomine insectary of the
      Laboratorio Nacional e Internacional de Referencia em Taxonomia de Triatomineos
      (FIOCRUZ), in Rio de Janeiro. Morphological studies were done with optical
      microscopy and scanning electron microscopy. Histological analyses used only
      optical microscopy. All of the species analyzed showed a predominance of
      hexagonal cells. The exchorion of Triatoma breyeri Del Ponte, T. costalimai
      Verano Galvao, and T. tibiamaculata (Pinto) consists of unornamented cells,
      overlapping or slightly separated, with a smooth, padded appearance. Meanwhile,
      in T. matogrossensis Leite Barbosa, T. sherlocki Papa, Juberg, Carcavallo,
      Cerqueira Barata, and T. williami Galvao, Souza Lima, the exchorion cells are
      ornamented on their entire surface with perforations and fissures. Egg histology
      showed undulations, pores, and orifices. The study helps to expand the generic
      and specific knowledge of the Triatominae subfamily. The characteristics
      identified in the exchorion of the eggshells can help separate close species.
      These new parameters will back the elaboration of future dichotomous keys, help
      to determine each vector species role and expand knowledge of the various
      species.

PMID- 18060310
TI  - Occurrence of Toxorhynchites guadeloupensis (Dyar Knab) in oviposition trap of
      Aedes aegypti (L.) (Diptera: Culicidae).
AB  - Toxorhynchites guadeloupensis (Dyar Knab), a poorly known mosquito species, was
      observed preying upon Aedes aegypti (L.) larvae, in an oviposition trap placed
      for routine dengue entomological surveillance, during 2003-2004 in the urban area
      of Boa Vista, Roraima, Brazil. This is the first report for Tx. guadeloupensis
      using Ae. aegypti oviposition traps as breeding places. This finding may have
      important consequences in the epidemiology and local dengue control since Ae.
      aegypti density is a basic variable in dengue prediction. Whether predation of Ae
      aegypti by Tx. guadeloupensis in the Amazon is of significance, is a question to
      be examined. Also, larval predation may be a cause for underestimation of the
      actual Ae aegypti numbers. Together these hypotheses need to be better
      investigated as they are directly related to dengue epidemiology, to the success
      of any outbreak prediction and surveillance program.

PMID- 18060311
TI  - [Microhabitat selection by ant-lion larvae Myrmeleon brasiliensis (Navas)
      (Neuroptera: Myrmeleontidae), in a Forest Reserve, Aquidauana, State of Mato
      Grosso do Sul].
AB  - The relative abundance, density, distribution pattern and relation among pit
      diameter and larvae body size of Myrmeleon brasiliensis Navas were evaluated in
      two microhabitats: sheltered and exposed. The total of 282 pits were found in
      sheltered microhabitat and only 50 in the exposed. The density of M. brasiliensis
      was between one and 43 individuals per m(2). The distribution pattern of larvae
      tended from pooled to regular distribution as the density increased. In both
      microhabitats the larvae body size was positively correlated with pit diameter.

PMID- 18060313
TI  - RNA polymerase I promoter and splice acceptor site recognition affect gene
      expression in non-pathogenic Leishmania species.
AB  - Leishmania (Sauroleishmania) tarentolae has biotechnological potential for use as
      live vaccine against visceral leishmaniasis and as a system for the over
      expression of eukaryotic proteins that possess accurate post-translational
      modifications. For both purposes, new systems for protein expression in this non
      pathogenic protozoan are necessary. The ribosomal RNA promoter proved to be a
      stronger transcription driver since its use yielded increased levels of
      recombinant protein in organisms of both genera Trypanosoma or Leishmania. We
      have evaluated heterologous expression systems using vectors with two different
      polypyrimidine tracts in the splice acceptor site by measuring a reporter gene
      transcribed from L. tarentolae RNA polymerase I promoter. Our data indicate that
      the efficiency of chloramphenicol acetyl transferase expression changed
      drastically with homologous or heterologous sequences, depending on the
      polypyrimidine tract used in the construct and differences in size and/or
      distance from the AG dinucleotide. In relation to the promoter sequence the
      reporter expression was higher in heterologous lizard-infecting species than in
      the homologous L. tarentolae or in the mammalian-infecting L. (Leishmania)
      amazonensis.

PMID- 18060314
TI  - High proportion of hepatitis C virus genotypes 1 and 3 in a large cohort of
      patients from Southern Brazil.
AB  - Hepatitis C virus (HCV) isolates have been divided into six genotypes (1 to 6).
      The duration of hepatitis C standard treatment is 48 weeks for patients infected
      with HCV genotype 1 vs 24 weeks for those infected with genotypes 2 and 3. A
      total of 1544 HCV isolates from chronic patients living in the southern Brazilian
      states of Rio Grande do Sul (RS, n=627) and Santa Catarina (SC, n=917) were
      genotyped by restriction fragment length polymorphism (RFLP) of polymerase chain
      reaction (PCR) products. In RS, 338 (53.9%; 95% CI 50.0-57.8%), 34 (5.4%; 95% CI
      3.8-7.4%) and, 255 (40.7%; 95% CI 36.9-44.6%) samples were from genotypes 1, 2,
      and 3, respectively. In SC, 468 (51%; 95% CI 47.8-54.2%), 26 (2.9%; 95% CI 1.9
      4.1%) and, 423 (46.1%; 95% CI 42.9-49.3%) samples were from genotypes 1, 2, and
      3, respectively. Genotyping results were confirmed by direct nucleotide
      sequencing of PCR products derived from 68 samples, without any discrepancy
      between PCR-RFLP and nucleotide sequencing methods. In conclusion, almost half of
      the hepatitis C patients from South of Brazil are infected by genotypes 2 and 3
      and, these results have important consequential therapeutic implications as they
      can be treated for only 24 weeks, not 48.

PMID- 18060316
TI  - Antimicrobial resistance profiles of enterococci isolated from poultry meat and
      pasteurized milk in Rio de Janeiro, Brazil.
AB  - The enterococci are important nosocomial pathogens with a remarkable capacity of
      expressing resistance to several antimicrobial agents. Their ubiquitous nature
      and resistance to adverse environmental conditions take account for their ability
      to colonize different habitats and for their potential for easy spreading through
      the food chain. In the present study we evaluated the distribution of species and
      antimicrobial susceptibility among enterococcal isolates recovered from food
      obtained in retail stores in Rio de Janeiro, Brazil. The following species were
      identified among 167 isolates obtained from poultry meat and 127 from pasteurized
      milk: Enterococcus faecalis (62.6%), E. casseliflavus (17.3%), E. durans (6.5%),
      E. gallinarum (3.0%), E. gilvus (2.4%), E. faecium (2.0%), E. hirae (1.4%), and
      E. sulfureus (1.0%). The overall percentages of antimicrobial resistant isolates
      were: 31.2 % to tetracycline, 23.8% to erythromycin, 11.3% to streptomycin, 4.3%
      to chloramphenicol, 3.9% to gentamicin, 1.4% to norfloxacin, 1.1% to imipenem,
      0.7% to ciprofloxacin, nitrofurantoin, and penicillin, and 0.4% to ampicillin.
      Intermediate resistance was detected in frequencies varying from 0.5% for
      linezolid to 58.2% for erythromycin. None of the isolates showed resistance to
      glycopeptides. High-level resistance to aminoglycosides was observed in 13.1% of
      the isolates. Multiresistance was observed in E. faecalis, E. casseliflavus, E.
      faecium, E. gallinarum, E. durans and E. gilvus.

PMID- 18060315
TI  - The involvement of tetA and tetE tetracycline resistance genes in plasmid and
      chromosomal resistance of Aeromonas in Brazilian strains.
AB  - This study analyzed the involvement of tetA and tetE genes in the tetracycline
      resistance of 16 strains of genus Aeromonas, isolated from clinical and food
      sources. Polymerase chain reactions revealed that 37.5% of the samples were
      positive for tetA, and also 37.5% were tetE positive. One isolate was positive
      for both genes. Only the isolate A. caviae 5.2 had its resistance associated to
      the presence of a plasmid, pSS2. The molecular characterization of pSS2 involved
      the construction of its restriction map and the determination of its size. The
      digestion of pSS2 with HindIII originated two fragments (A and B) that were
      cloned separately into the pUC18 vector. The tetA gene was shown to be located on
      the HindIII-A fragment by PCR. After transforming a tetracycline-sensitive strain
      with pSS2, the transformants expressed the resistance phenotype and harbored a
      plasmid whose size was identical to that of pSS2. The results confirmed the
      association between pSS2 and the tetracycline resistance phenotype, and suggest a
      feasible dissemination of tetA and tetE among strains of Aeromonas. This study
      suggests the spreading tetA and tetE genes in Aeromonas in Brazil and describes a
      resistance plasmid that probably contributes to the dissemination of the
      resistance.

PMID- 18060317
TI  - Anti-human immunodeficiency virus type 1 humoral immune response and highly
      active antiretroviral treatment.
AB  - Highly active antiretroviral treatment (HAART) of human immunodeficiency type 1
      (HIV-1) infection is very effective in controlling infection, but elimination of
      viral infection has not been achieved as yet, and upon treatment interruption an
      immediate rebound of viremia is observed. A combination of HAART with an immune
      stimulation might allow treatment interruption without this rebounding viremia,
      as the very low viremias observed with successful HAART may be insufficient to
      permit maintenance of a specific anti-HIV-1 immune response. The objective of
      this study was to compare the humoral immune response of individuals undergoing
      successful HAART (NF=no failure) with that of individuals with evidence of
      failure of therapy (FT) and to verify if the viremia peaks observed in
      individuals with therapy failure would act as a specific stimulus for the humoral
      anti-HIV-1 immune response. Antibodies binding to gp120 V3 genotype consensus
      peptides were more frequently observed for FT, mainly against peptides
      corresponding to sequences of genotypes prevalent in the Rio de Janeiro city
      area, B and F. HIV-1 neutralization of HIV-1 IIIB and of four primary isolates
      from Rio de Janeiro was less frequently observed for plasma from the NF than the
      FT group, but this difference was more expressive when plasma from individuals
      with detectable viremia were compared to that of individuals with undetectable
      viral loads in the year before sample collection. Although statistically
      significant differences were observed only in some specific comparisons, the
      study indicates that presence of detectable viremia may contribute to the
      maintenance of a specific anti-HIV-1 humoral immune response.

PMID- 18060318
TI  - Triatoma mexicana (Hemiptera: Reduviidae) in Guanajuato, Mexico: house
      infestation and seasonal variation.
AB  - Triatoma mexicana was described by Herrich-Schaeffer in 1848. In 1940, a male
      specimen was found in Hidalgo. In 1970, this species was recorded in the state of
      Queretaro. Later, it was registered in Guanajuato and San Luis Potosi. In the
      present paper we performed an investigation in 545 dwellings from three counties
      in the state of Guanajuato, Mexico, from March 2003 to May 2004. The search and
      capture of triatomines were seasonally performed indoors and outdoors.
      Entomological indexes were calculated. The risk and no risk relations between
      triatomine presence and housing construction materials were analyzed. Fourteen
      triatomines were collected indoors and 151 outdoors. The vectors were collected
      in houses built with either risky and non-risky materials. Adults go indoors but
      do not settle there, hence, no relationship was found between the building
      materials and infestation of houses. Conventional interventions like house
      improvement or insecticide spraying are not efficient for the control of T.
      mexicana, because its developmental cycle is accomplished outdoors in the area
      surrounding the houses.

PMID- 18060319
TI  - Niemann-Pick type C1 protein influences the delivery of cholesterol to the
      SREBP:SCAP complex.
AB  - The proposed role of Niemann-Pick type C1 protein (NPC1) in the delivery of low
      density lipoprotein (LDL) cholesterol to the sterol regulatory element binding
      protein (SREBP):SREBP cleavage activation protein (SCAP) complex in the
      endoplasmic reticulum has been largely based on indirect studies and remains
      contentious. The major aim of the present study was to assess whether NPC1 is
      involved in the delivery of LDL cholesterol to the SREBP:SCAP complex. A cell
      line stably expressing green fluorescence protein-SCAP was cultured in the
      presence of U18666A, which can induce a Niemann-Pick type C disease phenotype, in
      order to locate the SREBP:SCAP complex by fluorescence microscopy. Our major
      finding was that defective NPC1 caused a delay in the ability of LDL cholesterol
      to suppress SREBP processing. This was shown in a time-course experiment by the
      effect of LDL on green fluorescence protein-SCAP movement when cells were treated
      with pharmacological agents to induce a Niemann-Pick type C disease phenotype. We
      demonstrated directly by fluorescence microscopy that defective NPC1 causes a
      delay in LDL cholesterol delivery to the endoplasmic reticulum where SCAP senses
      cholesterol.

PMID- 18060320
TI  - The MTR A2756G polymorphism is associated with an increase of plasma homocysteine
      concentration in Brazilian individuals with Down syndrome.
AB  - Individuals with Down syndrome (DS) present decreased homocysteine (Hcy)
      concentration, reflecting a functional folate deficiency secondary to
      overexpression of the cystathionine ss-synthase gene. Since plasma Hcy may be
      influenced by genetic polymorphisms, we evaluated the influence of C677T and
      A1298C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR), of
      A2756G polymorphism in the methionine synthase gene (MTR), and of A80G
      polymorphism in the reduced folate carrier 1 gene on Hcy concentrations in
      Brazilian DS patients. Fifty-six individuals with free trisomy 21 were included
      in the study. Plasma Hcy concentrations were measured by liquid
      chromatography_tandem mass spectrometry with linear regression coefficient r(2) =
      0.9996, average recovery between 92.3 to 108.3% and quantification limits of 1.0
      micromol/L. Hcy concentrations >15 micromol/L were considered to characterize
      hyperhomocystinemia. Genotyping for the polymorphisms was carried out by
      polymerase chain reaction followed by enzyme digestion and allele-specific
      polymerase chain reaction. The mean Hcy concentration was 5.2 +/- 3.3 micromol/L.
      There was no correlation between Hcy concentrations and age, gender or MTHFR
      C677T, A1298C and reduced folate carrier 1 A80G genotype. However, Hcy
      concentrations were significantly increased in the MTR 2756AG heterozygous
      genotype compared to the MTR 2756AA wild-type genotype. The present results
      suggest that the heterozygous genotype MTR 2756AG is associated with the increase
      in plasma Hcy concentrations in this group of Brazilian patients with DS.

PMID- 18060321
TI  - The reciprocal interaction between sleep and type 2 diabetes mellitus: facts and
      perspectives.
AB  - Type 2 diabetes mellitus is a systemic disease characterized by intolerance to
      glucose and peripheral resistance to insulin. This endocrine disease affects
      fundamental mechanisms of the central nervous system and jeopardizes the balance
      of vital functions such as the cardiovascular and circadian rhythm. The increased
      prevalence of metabolic disorders in our society is aggravated by endemic
      voluntary postponement of bedtime and by the current sedentary lifestyle, leading
      to epidemic proportions of obese people. Diabetes and chronic loss of sleep share
      the fact that both affect millions and one is detrimental to the other. Indeed,
      sleep deficits have marked modulatory effects on glucose metabolism and insulin
      sensitivity and foster metabolic syndrome that culminates in sleep disorders like
      restless syndrome and sleep apnea, which in turn lead to poor sleep quality. We
      examine the hypothesis that these two worldwide emerging disorders are due to two
      interlinked cycles. In our paradigm, we establish an intimate relationship
      between diabetes and sleep disturbances and postulate possible mechanisms that
      provide support for this conjecture. In addition, we propose some perspectives
      about the development of the reciprocal interaction between predictor components
      of metabolic syndrome and sleep disturbances that lead to poor sleep quality. The
      ability to predict the development and identify or associate a given mode of
      sleep disturbance to diabetes would be a valuable asset in the assessment of
      both. Furthermore, major advances in care coupled with healthy lifestyles can
      ensure a higher quality of life for people with diabetes.

PMID- 18060322
TI  - Impairment of cytomegalovirus-specific cellular immune response as a risk factor
      for cytomegalovirus disease in transplant recipients.
AB  - Human cytomegalovirus (CMV) infection is common in most people but nearly
      asymptomatic in immunocompetent individuals. After primary infection the virus
      persists throughout life in a latent form in a variety of tissues, particularly
      in precursor cells of the monocytic lineage. CMV reinfection and occurrence of
      disease are associated with immunosuppressive conditions. Solid organ and bone
      marrow transplant patients are at high risk for CMV disease as they undergo
      immunosuppression. Antiviral treatment is effective in controlling viremia, but
      10-15% of infected patients can experience CMV disease by the time the drug is
      withdrawn. In addition, long-term antiviral treatment leads to bone marrow
      ablation and renal toxicity. Furthermore, control of chronic CMV infection in
      transplant recipients appears to be dependent on the proper recovery of cellular
      immunity. Recent advances in the characterization of T-cell functions and
      identification of distinct functional signatures of T-cell viral responses have
      opened new perspectives for monitoring transplant individuals at risk of
      developing CMV disease.

PMID- 18060323
TI  - Human-specific endogenous retroviruses.
AB  - This review focuses on a small family of human-specific genomic repetitive
      elements, presented by 134 members that shaped approximately 330 kb of the human
      DNA. Although modest in terms of its copy number, this group appeared to modify
      the human genome activity by endogenizing approximately 50 functional copies of
      viral genes that may have important implications in the immune response, cancer
      progression, and antiretroviral host defense. A total of 134 potential promoters
      and enhancers have been added to the human DNA, about 50% of them in the close
      gene vicinity and 22% in gene introns. For 60 such human-specific promoters,
      their activity was confirmed by in vivo assays, with the transcriptional level
      varying approximately 1000-fold from hardly detectable to as high as
      approximately 3% of a-actin transcript level. New polyadenylation signals have
      been provided to four human RNAs, and a number of potential antisense regulators
      of known human genes appeared due to human-specific retroviral insertional
      activity. This information is given here in the context of other major genomic
      changes underlining differences between human and chimpanzee DNAs. Finally, a
      comprehensive database, is available for download, of human-specific and
      polymorphic endogenous retroviruses is presented, which encompasses the data on
      their genomic localization, primary structure, encoded viral genes, human gene
      neighborhood, transcriptional activity, and methylation status.

PMID- 18060325
TI  - Reproductive health care for women with spina bifida.
AB  - Women with spina bifida have unique health care concerns and as the life
      expectancy of this population increases, they are transitioning from adolescence
      to womanhood and entering their reproductive years with little information about
      what to expect. Likewise, their health care providers do not have the benefit of
      evidence-based research that comprehensively addresses the issues these women may
      face related to reproduction or aging. Few studies have focused on the effects
      that spina bifida may have on these women's reproductive systems, nor has
      attention been paid to the effects that possible reproductive endocrine changes
      may have on their disability. Needless to say, concerns about sexuality, sexual
      function, and pregnancy are just as important to these women as they are to their
      able-bodied counterparts.

PMID- 18060324
TI  - Can spinal bupivacaine analgesia treatment make a difference on urinary bladder
      healing according to the intramuscular pethidine analgesia treatment in rats?
AB  - We designed a study to compare the healing levels found with intramuscular
      pethidine with those found with intrathecal local anesthetic treatments. The
      urinary bladder is suggested to be the most useful tissue in the evaluation of
      the effects of the drugs. Nineteen male, Sprague-Dawley rats weighing 200 C300 g
      were used in this study. A sagittal section was made in the urinary bladder after
      suitable anesthesia and laparotomy. Bladders were closed with 5-0 plain catguts 5
      min later. There were nine rats in the control group and pethidine (0.5 g/kg) was
      administered intramuscularly in the gluteal muscle region to treat pain after the
      operations. There were 11 rats in the study group and each received a spinal
      injection of 0.25% bupivacaine after the operation. Rats were followed for 7 days
      to define pain. Specimens, particularly the incised region of the bladder, were
      evaluated for inflammation and fibrosis. Grading scales were used for this
      purpose. Statistical analyses of the data were performed using the Chi-square
      test. Statistical analyses were nonsignificant for inflammation (p </= 0.151) and
      nonsignificant for fibrosis (p </= 0.105). The treatments may have the same
      effects on organ healing mechanisms. Statistical difference is not shown in this
      study, but use of other combinations of pain treatments to evaluate the healing
      may demonstrate which of these possibilities is true.

PMID- 18060326
TI  - The role of the nurse coordinator in spina bifida clinics.
AB  - There are numerous multidisciplinary spina bifida (SB) clinics (typically
      including urology, orthopedics, neurosurgery, developmental pediatrics,
      physiatry, nursing, social work, and physical and occupational therapy)
      throughout the U.S. Many SB clinics have a nurse coordinator. The coordinator's
      role is truly multifaceted. It goes far beyond coordinating the clinic visit in
      which patients and families are seen for care. The frequency of clinical visits
      varies from program to program, from a few hours once a month to a full day every
      week. This role encompasses many aspects of care for this complex patient
      population, which will be described.

PMID- 18060327
TI  - Transition to adulthood in spina bifida: changing roles and expectations.
AB  - Survival to adulthood for people with Spina Bifida now exceeds 85% due to
      improvements in medical and surgical management. Rates remain lower than expected
      for community participation, healthy lifestyle choices, employment and
      independent living. The importance of transition programming to help adolescents
      with disabilities prepare for adult life roles is now understood. Literature
      currently is mainly conceptual or descriptive, but informs the process of
      developing transition program models. The need for competent and effective adult
      care providers is discussed. Both the transition to adulthood and the transfer of
      care to adult care clinics are important and distinct components of spina bifida
      lifespan care.

PMID- 18060328
TI  - Nonsexual transmission of anogenital warts in children: a retrospective analysis.
AB  - The purpose was to evaluate the prevalence of sexual abuse in patients who were
      referred to a pediatric gynecologist for evaluation based on the clinical
      findings of anogenital warts. A retrospective analysis was performed on 131
      patients between the ages 6 month and 9 years referred to a pediatric
      gynecologist after the finding of anogenital warts by a clinical provider, parent
      or caregiver. A complete physical examination under colposcopy by a the same,
      trained pediatric gynecologist was completed, and a complete medical and family
      history including maternal and sibling history for evidence of Human
      Papillomavirus (HPV) and anogenital warts. The legal system completed a full
      investigation to examine the sexual abuse allegations. In 131 patients with
      anogenital warts, a maternal history of warts, cervical dysplasia or both was
      present in 66 (50%). The remaining patients had either a negative maternal
      history for HPV clinical findings (54 patients or 41.2%), or maternal history was
      unknown (11 patients, or 8.3%). Of 131 patients, 81 (61%) patients had a sibling.
      Of those with siblings 40 (49.4%) had warts and 41 (50.6%) did not. Forty-five
      (34%) of the cases had a positive maternal history for warts, dysplasia or both
      but also had a sibling. In that cohort, 32 (71%) of the siblings also had
      anogenital warts. Three of 131 patients were ruled suspicious for sexual abuse by
      the legal authorities but not confirmed. Of those three patients two were female
      and one was male. Two had no maternal history for HPV and both of these patients
      had a sibling without anogenital warts. Most cases of anogenital warts in
      children are likely to be the result of non-sexual transmission, namely prenatal
      mode. Thus, these patients should be handled differently by the legal system
      unless other reasons for suspicion exist. This study also showed the importance
      of maternal gynecologic history.

PMID- 18060329
TI  - Membranous dysmenorrhea: a case series.
AB  - The purpose was to illustrate the variability of hormonal contraception of
      patients that presented with membranous dysmenorrheal. A case analysis chart
      review was completed on six patients referred to a Pediatric Gynecologist in an
      academic setting. In each case the patient underwent a thorough pelvic and
      bimanual exam. Following the initial presentation, each patient continued to be
      followed on a regular visits. CASES: Two were using the transdermal contraceptive
      patch and oral contraceptive, but following the expulsion of decidual cast, they
      were both placed on depot medroxyprogesterone acetate (DMPA) without further
      complications. Three of the six cases were on DMPA prior to the similar
      occurrence of membranous dysmenorrheal and following this incident, continued on
      DMPA without further problems. The final case was on the transdermal patch prior
      to decidual cast expulsion and remained on this form of hormonal contraception
      without further complications. These cases indicate that membranous dysmenorrheal
      is not limited to the use of DMPA.

PMID- 18060330
TI  - TENS to the lateral aspect of the knees during stance attenuates postural sway in
      young adults.
AB  - Somatosensory input is known to be essential for postural control. The present
      study examined the effects on postural sway of sensory input delivered via
      transcutaneous electrical nerve stimulation (TENS) applied to the knees during
      stance. Electrodes from a dual-channel portable TENS unit were adhered to the
      skin overlying the lateral and medial aspect of both knees of 20 young healthy
      volunteers (mean age 24.0 years, standard deviation 4.0). Postural sway
      parameters were obtained during static bipedal stance with an AMTI force
      platform. Four stimulation conditions were tested with eyes open and with eyes
      closed: no TENS; TENS applied bilaterally; and TENS applied to either the right
      or the left knee. Participants underwent two eight-trial blocks, with each trial
      lasting 30 seconds. The order of conditions was randomized for each participant.
      Stimulation consisted of a biphasic symmetrical stimulus delivered at the sensory
      detection level, with a pulse duration of 200microsec and a pulse frequency of
      100Hz. The application of TENS induced significant reductions in mean sway
      velocity and in the medio-lateral dispersion of the center of pressure, with no
      corresponding effect on the anterior-posterior dispersion. These findings suggest
      that electrical stimulation delivered at the sensory detection level to the
      lateral aspects of the knees may be effective in improving balance control, and
      that this effect may be directionally specific.

PMID- 18060331
TI  - Can the intestine perform some functions of the kidney?
AB  - The majority of patients in countries like India and Pakistan with end-stage
      renal disease (ESRD) die without renal replacement therapy due to lack of
      adequate resources. The use of the intestinal mucosa as a semipermeable membrane
      for removal of urea and creatinine from the body has been previously studied
      using various types of intestinal lavage for gut dialysis. This study was
      undertaken in an animal model to assess the applicability, cost of therapy, and
      acceptability of the method for potential application in humans. Renal failure
      was induced in six dogs by bilateral ureteric ligation along with six healthy
      controls. Dialysis fluid was introduced per rectum as an enema, which was
      repeatedly administered. Clearances of serum creatinine and urea were assessed.
      Mean recovery of creatinine and urea in dialysate in the present study was around
      8.925 mmol/l and around 207.74 micromol//l, respectively. The mean clearances of
      serum creatinine and urea were, respectively, 0.0683 and 0.0633 ml/sec. Enteral
      dialysis was effective and, considering its minimal cost (monthly cost will be
      around US$35-40) vis a vis available methods, it holds promise for the treatment
      of patients with ESRD. The creation of an appendicostomy for repeated
      introduction of antegrade enemas would be a consideration.

PMID- 18060332
TI  - [Female patient with organic psychosyndrome and neurological focal signs after
      immunosuppressant therapy].
AB  - Cerebral toxoplasmosis nearly exclusively affects immunodeficient or
      immunocompromised patients. Mostly, it is a reactivation of latent toxoplasmosis.
      The pathogens, persisting in the reticuloendothelial system of heart and skeletal
      muscle cells, are causing a multifocal necrotizing encephalitis. The
      characteristic clinical features are organic psychosyndrome and focal
      neurological signs such as monoparesis, hemiparesis, aphasia, or seizures. Here
      we describe a 56-years-old patient who developed cerebral toxoplasmosis after
      receiving stem-cell transplantation treatment for acute myeloic leukemia, and we
      discuss the clinical features, differential diagnoses and therapeutic strategies.

PMID- 18060333
TI  - [An unusual complication of chronic pancreatitis].
AB  - Atraumatic rupture of the spleen is a rare, but life-threatening complication of
      pancreatitis. We report a case of an atraumatic spleenic rupture in chronic
      pancreatitis. A 41 year old man presented in the emergency room with abdominal
      pain and typical signs of acute pancreatitis. His medical history showed a
      chronic pancreatitis due to alcoholism with recurrent acute pancreatitic
      episodes. He denied any trauma in the recent past. In the next few hours he
      showed clinical signs of a severe hemorrhagic shock. The haemoglobin level fell
      from 9.4 to 3.0 g/dl. Abdominal ultrasound and abdominal CT scan showed free
      fluid. In the following laparotomy a splenectomy was performed due to splenic
      rupture. A histological examination of the spleen revealed no reason, that could
      explain the splenic rupture. Hence we assumed a spontaneous rupture. The reported
      case demonstrates that in acute pancreatitis and signs of shock it is necessary
      to rule out rupture of the spleen e.g. via ultrasound and abdominal CT scan. If
      there are signs of spleenic rupture, the only therapy of this life-threatening
      complication is instant operation to save patient's life.

PMID- 18060334
TI  - [Pharmacotherapy of obesity].
AB  - Diet, exercise and behavioral therapy are the basics for every treatment of
      obesity. If lifestyle intervention does not result in a weight loss of 5% within
      3 to 6 months, an additional pharmacotherapy can be considered. Treated patients
      should have a BMI >/=30 kg/m(2) or at least a BMI >/=27 kg/m(2) plus accompanying
      comorbidities, such as type 2 diabetes, dyslipidemia or hypertension. Current
      guidelines list orlistat, sibutramine and rimonabant as possible options for the
      pharmacotherapy of obesity. These compounds result in moderate weight reduction
      and improvement of cardiovascular risk profile. Especially the improvement of
      glucose metabolism can be considered as clinically relevant. Different side
      effects of the various compounds need to be considered before their use.
      Additional options for the pharmacotherapy of obesity are currently developed,
      their approval, however, is unlikely to happen within the next couple of years.

PMID- 18060337
TI  - [Preservation of hip prosthesis with local surgical revision and creation of a
      fistula persistens : an option for palliative treatment of periprosthetic
      infection in old, polymorbid patients?].
AB  - BACKGROUND: The number of implanted hip prostheses is increasing constantly. At
      the same time the patients are becoming older and older. Thus, also patients with
      periprosthetic infections are older and therefore sicker. Uniform guidelines for
      the treatment of infected arthroplasties are controversial. Empirical studies
      show that the explantation of the original prosthesis and implantation of a
      revision may be the option with the greatest chance of success. These very
      aggressive procedures may overburden the old, polymorbid patient. The aim of this
      study was to ascertain whether or not keeping the hip prosthesis in combination
      with local debridement, formation of a permanent fistula and long-term
      administration of antibiotics is a possible option for the treatment of infected
      hip prostheses in old and polymorbid patients. PATIENTS: Between 01.01.2004 and
      28.01.2007, 12 patients with periprosthetic infection after hip arthroplasty
      (PIH) were treated. Their average age was 79.8 years. Eleven patients were rated
      ASA III preoperatively. The prostheses were on average 23.8 weeks old when the
      first signs of infection occurred. In 10 cases the infection was caused by
      Staphylococcus (MRSA 3x). The main comorbidities were hypertension, diabetes,
      coronary heart disease and thyroid malfunction. RESULTS: After a mean 8.83
      months, six patients were deceased (average age 85.50 years). In five of the
      remaining six patients the fistula worked without any problem. In one case the
      fistula was occluded. None of the patients showed any sign of acute infection.
      All were able to walk with full weight-bearing on the affected hip. CONCLUSION:
      Restricting the indication to old, polymorbid patients, preservation of the
      arthroplasty in combination with local surgical debridement, permanent fistula
      and long-term systemic administration of antibiotics seems to be an alternative
      to explantation of the prosthesis with consecutive revision arthroplasty or
      resection arthroplasty.

PMID- 18060338
TI  - Specific fears and phobias in the general population: results from the
      Netherlands Mental Health Survey and Incidence Study (NEMESIS).
AB  - OBJECTIVE: To examine the prevalence rate, impairment, comorbidity, course of
      illness and determinants of eight specific phobia variants: animals (animal
      subtype); heights, water, storms (natural environment subtype); flying, enclosed
      spaces, being alone (situational subtype); and blood/injury (blood/injury
      subtype). METHOD: Data were obtained from the Netherlands Mental Health Survey
      and Incidence Study, a prospective study in the Dutch general population aged 18
      65 (N = 7,076). RESULTS: The most prevalent condition was specific phobia with a
      fear of heights (4.9%). On all parameters except duration, specific phobia with a
      fear of being alone emerged as the most severe condition. Phobias with fear of
      enclosed spaces and phobias with fear of blood showed a slightly greater
      likelihood of impairment, comorbidity and personality problems than phobias with
      fear of animals, heights, water or storms. CONCLUSION: The situational and
      blood/injury phobia subtypes appear to be a more significant index for
      impairments and for comorbid psychiatric disorders than the animal and natural
      environment phobia subtypes.

PMID- 18060339
TI  - The need for culture sensitive diagnostic procedures: a study among psychotic
      patients in Morocco.
AB  - OBJECTIVE: We examine the procedural validity of a standardized instrument for
      the diagnosis of psychotic disorders in Morocco. METHOD: Twenty-nine patients
      from Casablanca, Morocco, with a psychotic or mood disorder were examined using
      the Comprehensive Assessment of Symptoms and History (CASH) an adapted version
      using cultural formulation to make the instrument more culturally sensitive (CASH
      CS). Chance corrected agreement was calculated between diagnoses based on these
      two versions of CASH and independent clinical diagnoses according to local
      psychiatrists. RESULTS: Agreement for traditional CASH versus clinical diagnosis
      and for CASH versus CASH-CS was low (kappa = -0.19; SD 0.16 and kappa = 0.21; SD
      0.16, respectively). De CASH-CS, showed good agreement with clinical diagnosis
      (kappa = 0.79; SD 0.11). CONCLUSION: Standardized instruments for the assessment
      of psychosis such as the CASH may be liable to cultural misinterpretations. This
      may be relevant to the interpretation of the high incidence rates of
      schizophrenia among immigrants. SIGNIFICANT OUTCOMES: Agreement between a
      culturally naive version of a standardized diagnostic instrument for the
      assessment of psychosis and clinical diagnosis by Moroccan psychiatrists is poor.
      Adding additional probes and decision rules based on cultural formulation
      improves agreement with clinical diagnosis significantly. LIMITATIONS: The study
      was conducted in a small sample. Both versions of CASH were administered by the
      same interviewer in a single interview session.

PMID- 18060340
TI  - Mental health laws that require dangerousness for involuntary admission may delay
      the initial treatment of schizophrenia.
AB  - INTRODUCTION: A long duration of untreated psychosis (DUP) is associated with a
      worse prognosis, an increased risk of suicide and may be linked to serious
      violence. Mental health laws that require patients to be dangerous to themselves
      or to others before they can receive involuntary psychiatric treatment may make
      it more difficult to treat patients in their first episode of psychosis. METHODS:
      The mean and median DUP reported in studies of schizophrenia related psychoses
      were examined. A comparison was made between the DUP reported from jurisdictions
      that had an obligatory dangerousness criterion (ODC) and those with other
      criteria for involuntary treatment. RESULTS: The average mean DUP in samples from
      jurisdictions with an ODC was 79.5 weeks, but was only 55.6 weeks in those
      jurisdictions that did not have an ODC (P < 0.007). CONCLUSIONS: Mental health
      laws that require the patient to be assessed as dangerous before they can receive
      involuntary treatment are associated with significantly longer DUP. As reducing
      DUP is an intervention that can improve the prognosis of schizophrenia, this
      finding suggests that mental health laws should be amended to allow treatment on
      grounds other than dangerousness, at least in the crucial first episode of
      psychosis.

PMID- 18060341
TI  - The effects of bilateral caudal epidural S2-4 neuromodulation on female sexual
      function.
AB  - This is a pilot study to evaluate the effects of caudal epidural S2-4
      neuromodulation on female sexual function in a population of women with voiding
      dysfunction. We prospectively studied 36 consecutive female patients who
      underwent caudal epidural sacral neuromodulation. Patients received the Female
      Sexual Function Index (FSFI) questionnaire preoperatively and 6 months
      postoperatively. Six months after permanent implantation, the overall score on
      the FSFI improved by 52% (p = 0.05). Results were better in patients who
      underwent the treatment for voiding dysfunction compared to those who had pain as
      their primary complaint. In this group, the overall score improved by 157% (p =
      0.004). Stimulation of S2-4 by bilateral caudal epidural neuromodulation in this
      small group of women with voiding dysfunction, retention, and/or pelvic pain
      resulted in self-reported improvements in sexual function. Further studies are
      needed to evaluate the potential role of S2-4 sacral stimulation in the treatment
      of female sexual dysfunction.

PMID- 18060342
TI  - Histological changes in bone marrow after treatment of infliximab for rheumatoid
      arthritis.
AB  - To investigate histological evidence of bone remodeling in response to infliximab
      for rheumatoid arthritis (RA), bone marrow tissues were extracted from ten RA
      patients at the time of total knee arthroplasty after treatment of infliximab for
      an average of 16 months (range, 8-24 months). The patients had a mean age of 65.3
      years (range, 57-76 years) with 4.8 mg/week of methotrexate (MTX; 4-6 mg) and 3.8
      mg/day of prednisolone (2-5 mg). Control samples were obtained from ten RA
      patients who did not undergo infliximab therapy. These patients had an average
      age of 67.6 years (range, 59-78 years) and received 5.2 mg/week of MTX (4-6 mg)
      and 4.0 mg/day of prednisolone (2-5 mg). Histological examination of structural
      differences between the infliximab and control groups in bone marrow was
      performed using hematoxylin and eosin (H & E) to evaluate differences. In
      immunohistochemical examination, the expressions of tumor necrosis factor-alpha
      (TNF-alpha), interleukin-6 (IL-6), receptor activator of nuclear (kappa) B ligand
      (RANKL), osteoprotegerin (OPG), and osteopontin (OPN) were compared between both
      groups. H & E staining revealed that the bone marrow tissues of the RA patients
      who underwent infliximab therapy demonstrated newly formed thickness of
      interstitial septum among the trabeculae as compared with the control group.
      Moreover, immunohistochemical examinations revealed that TNF-alpha, IL-6, RANKL,
      OPG, and OPN were expressed in this newly formed bone after infliximab therapy.
      Therefore, treatment with infliximab improved the histological changes with
      respect to bone metabolism in the newly formed bone marrow tissues.

PMID- 18060343
TI  - Extracellular matrix of porcine pericardium: biochemistry and collagen
      architecture.
AB  - Pericardial tissue has been used to construct bioprostheses employed in the
      repair of different kinds of injuries, mostly cardiac. However, calcification and
      mechanical failure have been the main causes of the limited durability of cardiac
      bioprostheses constructed with bovine pericardium. In the course of this work, a
      study was conducted on porcine fibrous pericardium, its microscopic structure and
      biochemical nature. The general morphology and architecture of collagen were
      studied under conventional light and polarized light microscopy. The biochemical
      study of the pericardial matrix was conducted according to the following
      procedures: swelling test, hydroxyproline and collagen dosage, quantification of
      amino acids in soluble collagen, component extraction of the extracellular matrix
      of the right and left ventral regions of pericardium with different molarities of
      guanidine chloride, protein and glycosaminoglycan (GAG) dosage, sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and total GAG analysis. Microscopic
      analysis showed collagen fibers arranged in multidirectionally oriented layers
      forming a closely knit web, with a larger number of fibers obliquely oriented,
      initiating at the lower central region toward the upper left lateral relative to
      the heart. No qualitative differences were found between proteins extracted from
      the right and left regions. Likewise, no differences were found between fresh and
      frozen material. Protein dosages from left frontal and right frontal pericardium
      regions showed no significant differences. The quantities of extracted GAGs were
      too small for detection by the method used. Enzymatic digestion and
      electrophoretic analysis showed that the GAG found is possibly dermatan sulfate.
      The proteoglycan showed a running standard very similar to the small proteoglycan
      decorin.

PMID- 18060344
TI  - K+ channel expression in human breast cancer cells: involvement in cell cycle
      regulation and carcinogenesis.
AB  - K+ channels are a most diverse class of ion channels in the plasma membrane and
      are distributed widely throughout a variety of cells including cancer cells.
      Evidence has been accumulating from fundamental studies indicating that tumour
      cells possess various types of K+ channels and that these K+ channels play
      important roles in regulating tumor cell proliferation, cell cycle progression
      and apoptosis. Moreover, a significant increase in K+ channel expression has been
      correlated with tumorigenesis, suggesting the possibility of using these proteins
      as transformation markers and perhaps reducing the tumor growth rate by
      selectively inhibiting their functional activity. Significant progress has been
      made in defining the properties of breast K+ channels, including their
      biophysical and pharmacological properties and distribution throughout different
      phases of the cell cycle in breast cell line MCF-7. This review aims to provide a
      comprehensive overview of the current state of research into K+ channels/currents
      in breast cancer cells. The possible mechanisms by which K+ channels affect tumor
      cell proliferation and cell cycle progression are discussed.

PMID- 18060345
TI  - Synthesis and characterization of novel organosoluble and optically active
      aromatic polyesters containing L-methionine and phthalimide pendent groups.
AB  - 5-(4-Methylthio-2-phthalimidylbutanoylamino)isophthalic acid (5) as a novel
      diacid monomer containing phthalimide and flexible chiral groups was prepared by
      dehydration of L: -methionine and phthalic anhydride followed by reacting with
      thionyl chloride and then treating with 5-aminoisophthalic acid (5AIPA) in dry
      N,N-dimethylacetamide (DMAc). A series of novel polyesters (PEs) containing
      phthalimide group was prepared by the reaction of diacid monomer 5 with several
      aromatic diols via direct polyesterification with tosyl
      chloride/pyridine/dimethylformamide (DMF) system as condensing agent. The
      resulting new polymers were obtained in good yields and inherent viscosities
      ranging between 0.21 and 0.51 dLg(-1) were characterized with FT-IR, 1H NMR,
      elemental and thermogravimetric analysis techniques. These polymers are readily
      soluble in polar organic solvents such as DMAc, DMF, dimethyl sulfoxide and
      protic solvents such as sulfuric acid. Specific rotation experiments demonstrate
      the optical activity induction due to successful insertion of L-methionine in the
      structure of pendent groups. Thermogravimetric analysis showed that the 10%
      weight loss temperature in a nitrogen atmosphere were more than 315 degrees C,
      which indicates that the resulting PEs have good thermal stability.

PMID- 18060346
TI  - First characterisation of the active oligomer form of sulfur oxygenase reductase
      from the bacterium Aquifex aeolicus.
AB  - Sulfur oxygenase reductase (SOR) enzyme is responsible for the initial oxidation
      step of elemental sulfur in archaea. Curiously, Aquifex aeolicus, a
      hyperthermophilic, chemolithoautotrophic and microaerophilic bacterium, has the
      SOR-encoding gene in its genome. We showed, for the first time the presence of
      the SOR enzyme in A. aeolicus, its gene was cloned and recombinantly expressed in
      Escherichia coli and the protein was purified and characterised. It is a 16 homo
      oligomer of approximately 600 kDa that contains iron atoms indispensable for the
      enzyme activity. The optimal temperature of SOR activity is 80 degrees C and it
      is inactive at 20 degrees C. Studies of the factors involved in getting the fully
      active molecule at high temperature show clearly that (1) incubation at high
      temperature induces more homogeneous form of the enzyme, (2) conformational
      changes observed at high temperature are required to get the fully active
      molecule and (3) acquisition of an active conformation induced by the temperature
      seems to be more important than the subunit number. Differences between A.
      aeolicus SOR and the archaea SORs are described.

PMID- 18060347
TI  - Salinicoccus salitudinis sp. nov., a new moderately halophilic bacterium isolated
      from a saline soil sample.
AB  - A novel pale-yellow-pigmented, moderately halophilic, facultatively alkaliphilic,
      non-motile, non-spore-forming, catalase- and oxidase-positive, obligately aerobic
      Gram-positive coccus, strain YIM-C678T was isolated from a saline soil sample
      collected from a hypersaline habitat in the Qaidam basin, northwest China. The
      organism grew at 4-37 degrees C and pH 6.0-11.0, with optimum growth at 25
      degrees C and pH 8.0. Strain YIM-C678T grew optimally in the presence of 10-12%
      (w/v) NaCl and growth was observed in 1-25% (w/v) NaCl. The cell wall murein type
      was L: -Lys-Gly5. Major cellular fatty acids were anteiso-C15:0, iso-C15:0, iso
      C16:0 and C16:0. Menaquinone 6 (MK-6) was the major respiratory quinone. The DNA
      G + C content was 46.5 mol%. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that the strain YIM-C678T belonged to the family
      Staphylococcaceae and was most closely related to the eight described species of
      the genus Salinicoccus with sequence similarities from 92.2 (S. luteus YIM
      70202T) to 97.5% (S. kunmingensis YIM Y15T). The DNA-DNA relatedness between
      strain YIM-C678T and S. kunmingensis YIM Y15T was 35.4%. Chemotaxonomic data and
      16S rRNA gene sequence analysis supported the affiliation of strain YIM-C678T
      with the genus Salinicoccus. The combination of phylogenetic analysis, phenotypic
      characteristics, chemotaxonomic differences and DNA-DNA hybridization data
      supported the view that the bacterium represents a novel species of the genus
      Salinicoccus, for which the name Salinicoccus salitudinis sp. nov. is proposed,
      with YIM-C678T (=DSM 17846 = CGMCC 1.6299) as the type strain.

PMID- 18060348
TI  - Transient expression of AtNCED3 and AAO3 genes in guard cells causes stomatal
      closure in Vicia faba.
AB  - Abscisic acid (ABA) regulates stomatal closure in response to water loss. Here,
      we examined the competence of guard cells to synthesize ABA, using two
      Arabidopsis ABA biosynthetic enzymes. 35S pro::AtNCED3-GFP and AAO3-GFP were
      introduced into guard cells of broad bean leaves. AtNCED3-GFP expression was
      detected at the chloroplasts, whereas green fluorescent protein (GFP) and AAO3
      GFP were in the cytosol. The stomatal aperture was decreased in AtNCED3-GFP- and
      AAO3-GFP-transformed guard cells. This indicated that ABA biosynthesis is
      stimulated by heterologous expression of AtNCED3 and Arabidopsis aldehyde oxidase
      3 (AAO3) proteins, which both seem to be regulatory enzymes for ABA biosynthesis
      in these cells. Furthermore, stomatal closure by the expression of AtNCED3 and
      AAO3 suggested that the substrates of the enzymes are present and native ABA
      biosynthesis enzymes are active in guard cells.

PMID- 18060350
TI  - Effect of soil moisture on leaf ecophysiology of Parasenecio yatabei, a summer
      green herb in a cool-temperate forest understory in Japan.
AB  - Leaf physiological and gas-exchange traits of a summer-green herbaceous
      perennial, Parasenecio yatabei, growing along a stream were examined in relation
      to leaf age. In its vegetative phase, the aerial part of this plant consists of
      only one leaf and provides an ideal system for the study of leaf longevity.
      Volumetric soil water content (SWC) decreased with increasing distance from the
      stream, whereas relative light intensity was nearly constant. The light-saturated
      net CO2 assimilation rate (Asat) and leaf stomatal conductance (gs) were
      approximately 1.5-fold and 1.4-fold higher, respectively, in the lower slope near
      the mountain stream than in the upper slope far from the mountain stream. The
      lifespan of aerial parts of vegetative plants significantly increased with
      decreasing SWC. The leaf mass-based nitrogen content of the leaves (N mass) was
      almost constant (ca. 2.2%); however, the maximum carboxylation rate by ribulose
      1,5-biphosphate carboxylase/oxygenase (rubisco) (V cmax) and photosynthetic
      nitrogen use efficiency (PNUE, A sat/N area) decreased more slowly in the upper
      slope than in the lower slope. The higher leaf photosynthetic activity of P.
      yatabei plants growing lower on the slope leads to a decrease in V (cmax) and
      PNUE in the early growing season, and to a shorter leaf lifespan.

PMID- 18060349
TI  - Salt-induced plasticity of root hair development is caused by ion disequilibrium
      in Arabidopsis thaliana.
AB  - Root hair development is controlled by environmental signals. Studies on root
      hair plasticity in Arabidopsis thaliana have mainly focused on phosphate and iron
      deficiency. Root hair growth and development and their physiological role in
      response to salt stress are largely unknown. Here, we show that root epidermal
      cell types and root hair development are highly regulated by salt stress. Root
      hair length and density decreased significantly in a dose-dependent manner on
      both primary roots and junction sites between roots and shoots. The root hair
      growth and development were sensitive to inhibition by ions but not to osmotic
      stress. High salinity also alters anatomical structure of roots, leading to a
      decrease in cell number in N positions and enlargement of the cells. Moreover,
      analysis of the salt overly sensitive mutants indicated that salt-induced root
      hair response is caused by ion disequilibrium and appears to be an adaptive
      mechanism that reduces excessive ion uptake. Finally, we show that genes WER,
      GL3, EGL3, CPC, and GL2 might be involved in cell specification of root epidermis
      in stressed plants. Taken together, data suggests that salt-induced root hair
      plasticity represents a coordinated strategy for early stress avoidance and
      tolerance as well as a morphological sign of stress adaptation.

PMID- 18060351
TI  - Pediatric inguinal hernia repair-a critical appraisal.
AB  - Inguinal hernia repair in infants and babies is a routine operation, but many
      issues have not been addressed scientifically. Thus, it is not known, e.g., if
      all children with a hernia should be operated on, what is the best timing of
      surgery, or if the operation should be performed with an open approach or
      laparoscopically. The review is a critical discussion of these and other issues
      in pediatric herniorrhaphy pointing out the need for further research.

PMID- 18060352
TI  - Postoperative hematoma following inguinal herniorrhaphy: patient characteristics
      leading to increased risk.
AB  - BACKGROUND: Although relatively infrequent, groin hematoma following inguinal
      herniorrhaphy is a morbid complication with major ramifications of mesh infection
      and hernia recurrence. We have sensed an increasing frequency of this
      complication in our tertiary referral practice and sought to determine whether or
      not significant risk factors could be identified. METHODS: In this matched case
      control study (1995-2003), we identified 53 patients with groin hematomas and
      paired them with 106 age- and gender-matched controls. Patient and procedure
      characteristics were analyzed using chi-square and both univariate and
      multivariable, conditional logistic regression analysis. RESULTS: The 53 patients
      developing groin hematoma following inguinal hernia repair (mean age=65, range 22
      87, 90% male) were well matched with 106 controls (mean age=65, range 22-87, 90%
      male). There was no significant difference in the location (left, right,
      bilateral), type (direct, indirect, pantaloon, first repair, or recurrent), or
      technique of hernia repair (Bassini, Lichtenstein, mesh plug, endoscopic, or
      McVay) between groups. While univariate analysis identified Coumadin usage
      (P<0.001, hazard ratio 19.1), valvular disease (P<0.001, hazard ratio 10.9),
      atrial fibrillation (P=0.02, hazard ratio 4.2), vascular disease (P=0.04, hazard
      ratio 2.2), blood abnormalities (P=0.02, hazard ratio 3.2), and previous bleeding
      episodes (P=0.02, hazard ratio 4.9) as significant factors, only preoperative
      Coumadin usage was important in multivariate analysis. CONCLUSION: The crucial
      risk factor for groin hematoma developing in patients undergoing inguinal hernia
      repair is preoperative need for Coumadin therapy. Although the perioperative
      management of anticoagulation in patients undergoing inguinal herniorrhaphy is
      not clearly defined, meticulous management of patients requiring Coumadin therapy
      seems prudent.

PMID- 18060353
TI  - Management of enema tip-induced rectourethral fistula with gluteus maximus flap:
      report of a case.
AB  - Rectourethral fistulas are uncommon and pose a challenging treatment problem. We
      report the case of 68-year-old man with rectourethral fistula following enema tip
      induced rectal injury. We treated the patient with an alternative surgical method
      used to close poorly healing defects between the urethra and rectum, by means of
      a muscular flap of the gluteus maximus muscle. The postoperative course was
      uneventful. He remained well and asymptomatic 6 months after the surgery. This
      technique is superior to gracilis muscle transposition, regarding the richer
      blood supply, anatomic neighborhood, technical simplicity, and avoidance of
      unnecessary incisions. Gluteus maximus muscle flap seems to be a good alternative
      technique in the treatment of iatrogenic rectourethral fistula.

PMID- 18060356
TI  - When can local excision be considered adequate for treatment of non advanced low
      rectal cancer (NALRC)?

PMID- 18060360
TI  - Total rectal lumen obliteration after stapled haemorrhoidopexy: a cautionary
      tale.
AB  - We describe obliteration of the rectal lumen during stapled haemorrhoidopexy in a
      patient with marked mucosal prolapse. The complication was recognised immediately
      and continuity was restored by performing a limited Delorme's procedure. The
      possible cause of this complication is explored and serves as a reminder that
      meticulous technique is required when performing stapled haemorrhoidopexy to
      prevent potentially disastrous complications.

PMID- 18060361
TI  - Proctalgia in a patient with staples retained in the puborectalis muscle after
      STARR operation.
AB  - Stapled transanal rectal resection (STARR) is a novel surgical technique for the
      treatment of intussusception and rectocele causing obstructed defecation. In this
      procedure, a double full-thickness rectal resection is performed transanally
      using two circular staplers. We describe the case of a patient complaining of
      persistent pain, tenesmus and fecal urgency after STARR. The patient also had an
      external rectal prolapse requiring an Altemeier rectosigmoid resection; during
      this operation we found and removed several staples that had stuck to the
      puborectalis muscle during STARR. Some degree of muscle inflammation was found at
      histological analysis. The patient recovered fully after this reintervention.
      Among the complications reported after STARR, the present one had not previously
      been described. The retained staples might have caused proctalgia in this
      patient.

PMID- 18060357
TI  - Inflammatory bowel disease: the problems of dysplasia and surveillance.
AB  - Patients with ulcerative colitis and colonic Crohn's disease are at an increased
      risk of developing colorectal malignancy. The reporting of such cases in the
      literature has led to the identification of a number of risk factors for the
      development of mucosal dysplasia and cancer. The diagnosis of dysplasia and the
      subsequent management, however, are not without controversy, as is the practice
      of surveillance colonoscopy that is commonly performed in an attempt to reduce
      the risk of cancer.

PMID- 18060362
TI  - En bloc resection of abdominal aorta and paraaortic lymph node metastasis of
      sigmoid cancer.
AB  - The surgical management of colorectal metastasis is becoming a widespread
      practice in oncology. Synchronous resection of metastasis together with invaded
      major vessels (aorta) is still considered an extremely aggressive procedure. We
      demonstrate that en bloc resection of invaded aorta and paraaortic lymph node
      metastasis can be safely performed. The literature from experiences with similar
      techniques is also discussed.

PMID- 18060363
TI  - Implicating chromosomal aberrations with meningioma growth and recurrence:
      results from FISH and MIB-I analysis of grades I and II meningioma tissue.
AB  - The fluorescence in situ hybridization (FISH) technique was used in 111 WHO
      grades I and II meningioma patients. Clinical, radiological, pathological, and
      immunohistochemical data were compared to aberrations of chromosomes 1p, 14q, and
      22q determined by FISH. Significant differences for MIB-1 labeling were found
      between grades I and II tumors (p < 0.001), and between grade I tumors that
      recurred and those that did not recur (p < 0.001). Chromosomal aberrations were
      detected with FISH analysis in nearly 50% of grade I, and in 93% of grade II
      meningiomas. The numbers of chromosomal aberrations correlated significantly to
      MIB-1 (p < 0.001), with signs of grossly invasive tumor growth (p < 0.001), and
      with tumor recurrence (p < 0.01). The findings suggest that adding FISH analysis
      may allow better prediction of possible meningioma recurrence and may be a useful
      adjunct for therapy decisions.

PMID- 18060364
TI  - Compression stockings to prevent post-thrombotic syndrome: a role for
      anticoagulation clinics?
AB  - Anticoagulation clinics are increasingly used to manage oral anticoagulant
      therapy in patients with venous thromboembolic disease (VTE). Such clinics may be
      in a position to assume greater responsibility for other aspects of the long-term
      management of VTE, including prevention of post-thrombotic syndrome (PTS).
      Current guidelines suggest use of graduated elastic compression stockings with a
      pressure of 30-40 mm Hg at the ankle for 2 years following the diagnosis of deep
      vein thrombosis (DVT) to prevent PTS. A survey of anticoagulation clinic
      providers was conducted to determine to what extent patients with DVT are
      prescribed compression stockings and by whom, and the degree of compression and
      duration of therapy prescribed. Survey results show a very low rate of use of
      compression stockings in patients with DVT, and limited adherence to current
      recommendations for strength and duration of use. We believe that healthcare
      providers practicing in anticoagulation clinics should be encouraged to expand
      their scope of practice into a more comprehensive model of antithrombosis care,
      including prevention of PTS. By doing so, the extent of use of compression
      stockings might be increased, and adherence to current guidelines for strength
      and duration of compression might be improved.

PMID- 18060365
TI  - Purification and bioactivity of exendin-4, a peptide analogue of GLP-1, expressed
      in Pichia pastoris.
AB  - Exendin-4, a peptide analogue of glucagon-like peptide-1 (GLP-1), has been
      developed for treatment of type 2 diabetes. Herein, the secretive exendin-4
      fusion protein, expressed by methanol induction in Pichia pastoris system, was
      purified to homogeneity by chromatography followed by enterokinase cleavage of
      the fusion protein and subsequent purification of the recombinant exendin-4.
      Purity of the recombinant exendin-4 was 95.6%. Bioactivity assay revealed that it
      had glucose-lowering and insulin-releasing action in vivo.

PMID- 18060366
TI  - Total antioxidant status and 8-hydroxy-2'-deoxyguanosine levels in gingival and
      peripheral blood of periodontitis patients.
AB  - INTRODUCTION: The aim of this study was to determine 8-OHdG concentration as a
      biomarker of oxidant-induced DNA damage and to assess total antioxidant status
      (TAS) in gingival and peripheral blood during periodontal lesion. MATERIALS AND
      METHODS: The study included 56 untreated periodontitis patients (26 with
      aggressive periodontitis, and 30 with chronic periodontitis (CP). The control
      group consisted of 25 healthy volunteers without pathological changes in the
      periodontium. Competitive ELISA was used to measure 8-OHdG. A colorimetric method
      based on the reduction of ABTSo+ radical cation generation was used to measure
      TAS. RESULTS: Significantly higher 8-OHdG concentrations were detected in the
      gingival blood in both groups of patients with periodontitis than in the control
      group. Subjects with CP had significantly decreased TAS levels in the gingival
      blood compared with the control group. A significantly decreased TAS level in the
      peripheral blood in both patient groups compared with the control group was
      found. Significant positive correlation between TAS levels in venous and gingival
      blood in all the periodontitis patients and in the CP group was observed.
      CONCLUSIONS: The oxidative burst in periodontitis may lead to significant local
      damage to nucleic acids. The significantly decreased TAS level in the gingival
      blood of CP patients compared with the healthy subjects suggests the possibility
      of a significant decrease in local antioxidant system capacity during the course
      of periodontitis. The decreased TAS level in the peripheral blood in the group of
      all patients with periodontitis may be one of the pathogenic mechanisms
      underlying the links between periodontal disease and several systemic diseases
      for which periodontitis is regarded as a independent risk factor.

PMID- 18060367
TI  - The influence of different culture microenvironments on the generation of
      dendritic cells from non-small-cell lung cancer patients.
AB  - INTRODUCTION: Monocyte-derived dendritic cells (DCs) are currently under
      extensive evaluation as cell vaccines for cancer treatment. Many protocols
      regarding DCs generation in vitro with different protein components, especially
      autologous proteins, have been described. On the other hand, active tumor-derived
      factors in patients' serum could impair monocytes, which might result in their
      abrogated differentiation into DCs in vitro. MATERIALS AND METHODS: Autologous
      DCs from non-small-cell lung cancer (NSCLC)-bearing patients were generated in
      different culture microenvironments. Peripheral blood mononuclear cells (PBMCs)
      were cultured in the presence of interleukin-4 and granulocyte-monocyte
      stimulating factor with supplementation of 10% autologous serum, 10% allogenic
      serum, or 2% human albumin. The course of apoptosis, phagocytic ability, and the
      immunophenotype of the generated DCs were analyzed using flow cytometric methods.
      RESULTS: After 48 h of culture, we found a lower percentage of CD1a+/CD14+ and a
      higher percentage of CD1a+/CD14(-) cells in the culture supplemented with human
      albumin than in the cultures supplemented with serums. The lowest CD14 antigen
      expression was found in the human albumin-supplemented 48-h cultures. After 48 h
      in the cultures carried out with human albumin we found significantly higher
      percentages of AV+/PI+ cells and AV(-)/PI+ cells than in cultures supplemented
      with autologous or allogenic serum. We also noted that the expression of FITC
      dextran after 4 and 24 h of incubation was significantly higher in the cultures
      supplemented with both serums than in the HA-SC. The percentage of semi-mature
      DCs and of CD83 expression was lowest in the culture supplemented with 2% human
      albumin. CONCLUSIONS: The kind of culture supplementation had a great impact on
      the apoptosis of cultured PBMCs. It could also influence the yield of monocyte
      derived DCs. It was also confirmed that autologous and allogenic serums provide
      suitable microenvironments for the generation of autologous DCs from NSCLC
      patients. The choice of culture supplementation for DC generation is still
      unsolved and further studies should be undertaken.

PMID- 18060368
TI  - Immunomodulation by alpha(1)-proteinase inhibitor: lack of chemotactic effects of
      recombinant human alpha(1)-proteinase inhibitor from yeast on human peripheral
      blood granulocytes.
AB  - INTRODUCTION: Recombinant alpha(1)-proteinase inhibitor, clinically developed for
      inhalative augmentation therapy in patients with alpha(1)-proteinase inhibitor
      deficiency or cystic fibrosis, may directly contribute to leukocyte accumulation
      as it may function as a chemoattractant. The migratory effects of yeast-derived
      human recombinant alpha(1)-proteinase inhibitor on human peripheral blood
      neutrophils and eosinophils were therefore tested in vitro. MATERIALS AND
      METHODS: Human peripheral blood leukocytes were prepared from forearm venous
      blood and tested for migration toward various preparations of yeast-derived
      recombinant alpha(1)-proteinase inhibitor in modified Boyden-chamber micropore
      filter assays. RESULTS: No direct effects of yeast-derived recombinant human
      alpha(1)-proteinase inhibitor on in vitro migration of isolated neutrophils or
      eosinophils were seen. CONCLUSIONS: The lack of direct chemotactic effects of
      recombinant human alpha(1)-proteinase inhibitor despite anti-inflammatory effects
      in other biological activities of leukocytes may contribute to the preserved
      antibacterial defense mechanisms observed in patients under experimental
      augmentation therapy with inhaled alpha(1)-proteinase inhibitor.

PMID- 18060369
TI  - DNA vaccines: are they still just a powerful tool for the future?
AB  - Vaccination is historically one of the most successful strategies for the
      prevention of infectious diseases. For safety reasons, modern vaccinology tends
      toward the usage of inactivated or attenuated microorganisms and uses
      predominantly subunit vaccines. The antigens need to be clearly defined, pure,
      stable, appropriately composed, and properly presented to the immune system of
      the host. Differing ratios of various proportions between specific CD4+ and CD8+
      T cell responses are essential for conferring the required protection in the case
      of individual vaccines. To stimulate both CD4+ and CD8+ T cells, the antigens
      must be processed and presented to both antigen-presentation pathways, MHC I and
      MHC II. Protein antigens delivered by vaccination are processed as extracellular
      antigens. However, extracellularly delivered antigen can be directed towards
      intracellular presentation pathways in conjugation with molecules involved in
      antigen cross-presentation, e.g. heat shock proteins, or by genomic-DNA
      vaccination. In this overview, current knowledge of the host immune response to
      DNA vaccines is summarized in the introduction. The subsequent sections discuss
      techniques for enhancing DNA vaccine efficacy, such as DNA delivery to specific
      tissues, delivery of DNA to the cell cytoplasm or nucleus, and enhancement of the
      immune response using molecular adjuvants. Finally, the prospects of DNA
      vaccination and ongoing clinical trials with various DNA vaccines are discussed.

PMID- 18060370
TI  - Recent discoveries in the genetics of melanoma and their therapeutic
      implications.
AB  - The incidence of cutaneous malignant melanoma, tumors arising from melanocytes,
      has increased markedly over the past few years in many countries. Although early
      melanoma is curable through surgical excision, the prognosis of advanced melanoma
      is very poor, this tumor being resistant to current therapies. Thus there is a
      need for new therapies to improve the treatment of advanced melanoma. This review
      provides an overview of recent discoveries in the genetics of melanoma which
      could offer new therapeutic opportunities.

PMID- 18060371
TI  - Alterations in the expression of signal-transducing CD3 zeta chain in T cells
      from patients with chronic inflammatory/autoimmune diseases.
AB  - The CD3 zeta chain, a component of the T cell receptor (TCR)/CD3 complex, is
      considered to be a limiting factor in the assembly and transport of the TCR/CD3
      complex to the cell surface and is crucial to receptor signaling function. Recent
      studies have demonstrated altered expression and function of this signal
      transduction molecule in T and natural killer cells in patients with chronic
      inflammatory/autoimmune diseases. In this review, current knowledge concerning
      the expression of CD3 zeta chain as well as the mechanisms responsible for
      abnormal expression of this molecule in systemic lupus erythematosus, rheumatoid
      arthritis, and childhood idiopathic nephrotic syndrome are summarized.

PMID- 18060372
TI  - Regulation of local immunity by airway epithelial cells.
AB  - Epithelial cells are the first line of defense against invading microbial
      pathogens. They are important contributors to innate mucosal immunity and
      generate various and sophisticated anti-microbial defense mechanisms, including
      the formation of a tight barrier and secretion of anti-microbial substances as
      well as inflammatory mediators. To provide these active defense mechanisms,
      epithelial cells functionally express various pattern-recognition receptors. Toll
      like receptors have been shown to recognize conserved microbial patterns
      mediating inducible activation of innate immunity. Mucosal surfaces, however, are
      prone to contact with pathogenic as well as non-pathogenic microbes and,
      therefore, immune-recognition principles have to be strictly regulated to avoid
      uncontrolled permanent activation. This review will focus on mechanisms by which
      epithelial cells regulate mucosal immune responses, thus creating an organ
      specific microenvironment. This includes local adaptations in microbial
      recognition, regulation of local immune homeostasis, and modulation of antigen
      presenting cells and adaptive immune responses. These regulatory mechanisms serve
      the special needs of controlled microbial recognition in mucosal compartments.

PMID- 18060374
TI  - Construction and characterization of a goat mammary gland cDNA library.
AB  - A lactating goat mammary gland cDNA library was constructed by using a modified
      commercially available cDNA library construction kit protocol. The resulting
      clones were sequenced and functionally analyzed through cross-species genomic
      comparison to assess (1) the capacity and functional quality of the constructed
      library for subsequent research and (2) the efficiency of the procedural
      modifications. The study resulted in the construction of a high-quality mammary
      gland cDNA library, which was characterized by (1) the total recombinants number
      of 1.4 x 10(7) colony-forming units (cfus) that was at least 10 times greater
      than the number expected from the application of the standard kit protocol, (2)
      the recombinants rate of 96%, and (3) the average insert size of 1,082 bp. BLAST
      analysis of sequenced clones against GenBank databases determined 55.7% of clone
      redundancy, 22 known function gene clusters, and 29 novel gene clusters. The
      analysis of the primary gene expression profile showed that 59% of the tested
      clones were genes that coded for milk proteins while 16% of the clones coded for
      ribosomal, metabolism, immune response, and translation proteins. The remaining
      25% of the tested clones were described as novel genes. Cross-species comparison
      showed that 77% of characterized gene clusters were successfully identified by
      using resources from other ruminants and unrelated species. This outcome is in
      consonance with the common belief that the genomic resources that have been
      generated across species are potentially powerful tools that could be used for
      enhancing the molecular understanding of less genomically studied species, such
      as goat.

PMID- 18060375
TI  - Low HDL levels and the risk of death, sepsis and malignancy.
AB  - BACKGROUND: High density lipoprotein (HDL) plays an important role as an anti
      atherogenic molecule, but also possesses anti-inflammatory and anti-angiogenic
      properties. The effect of extremely low levels of HDL on the risk of sepsis and
      malignancy were therefore examined. METHODS: A retrospective analysis of patients
      hospitalized at the Edith Wolfson Medical center was conducted. Patients were
      divided into Group 1: 108 patients with serum HDL levels < or =20 mg/dl. Group 2:
      96 patients with serum HDL levels > or =65 mg/dl. Medical history and laboratory
      data was recorded. RESULTS: The mean HDL levels in Group 1 were 16.1 +/- 33 mg/dl
      compared to 74.9 +/- 12.6 mg/dl in Group 2. Using a multivariate logistic
      regression analysis, low HDL was inversely associated with death (OR 0.96, 95%
      0.93-0.99, P = 0.02), 3.98 fold increase in odds of fever (OR 3.98, 95% CI 1.3
      11.8, P = 0.01), and 6.7-fold increase in the risk of cancer (OR 6.68, 95% CI 1.8
      24.5, P = 0.004). HDL serum levels were inversely associated with sepsis. For
      each 1 mg/dl increase in HDL, a relative 11% decrease in odds of sepsis was
      observed (OR 0.886, 95% CI 0.8-0.976, P = 0.01). CONCLUSIONS: Extremely low serum
      HDL levels (< or =20 mg/dl) are associated with an increased risk of death,
      sepsis and malignancy.

PMID- 18060376
TI  - The case for statin therapy in chronic heart failure.
AB  - Both primary and secondary prevention studies have provided a wealth of evidence
      that statin therapy effectively reduces cardiovascular events. However, this
      general statement on the efficacy and safety of statin treatment has not been
      validated in patients with chronic heart failure (CHF). Recently, numerous statin
      trials have reported analysis on CHF parameters and numerous CHF trials have
      performed analysis on baseline statin use. In this article, we will review the
      currently available evidence from a pathophysiological as well as clinical
      perspective, building a case for and against the use of statins in CHF. From a
      pathophysiological perspective, we will discuss the known association of
      cholesterol and mortality, the ubiquinone, and the endotoxin-lipoprotein
      hypothesis. From a clinical perspective, we will discuss the observational
      studies, subgroup analysis of large randomized controlled trials, prospective
      randomized trials in CHF patients, and the future perspectives of the large
      European statin studies focussing on the statin therapy in CHF.

PMID- 18060377
TI  - Productivity loss as a major component of disease-related costs in patients with
      hypercholesterolemia in Germany.
AB  - OBJECTIVE: Hypercholesterolemia is a common risk factor for cardiovascular
      diseases; however, there are only few data available on associated costs. The
      objective of this study is, therefore, to analyse direct and indirect costs in
      patients with hypercholesterolemia and to determine predictors of costs. METHODS:
      The ORBITAL Study is a randomised controlled trial evaluating the effectiveness
      of a compliance-enhancing program in patients with statin therapy. Consecutive
      patients eligible for statin therapy according to the Joint European Guidelines
      were enrolled nationwide in 1961 primary care practices in Germany. For the
      present cost-of-illness analysis, patients were asked retrospectively about
      medical resource use and employment status in the 6 months preceding enrollment.
      The perspective chosen was societal. Factors associated with costs were
      determined using linear regression. RESULTS: A total of 7,640 patients (56% men,
      mean age 60 +/- 10 years, and 44% women, 64 +/- 10 years) were included. Of these
      patients, 32% were employed, 17% had a history of myocardial infarction, 7% a
      history of stroke, 58% had hypertension, and 29% diabetes. Total disease-related
      costs amounted to a mean of 2,498 +/- 4,898 Euros per patient over 6 months,
      comprising direct (44%) and indirect (56%) costs. Disease-related early
      retirement was responsible for 42% of costs, followed by hospital visits (19%),
      medication (15%), workdays lost (14%), physician visits (5%), outpatient therapy
      (2%), and rehabilitation (2%). In multivariable analyses, factors associated with
      direct costs included coronary interventions, risk stratum, and medical history.
      Factors associated with indirect costs included disease-related early retirement,
      other socio-economic and lifestyle factors, coronary interventions, risk stratum,
      and medical history. CONCLUSION: The considerable economic burden associated with
      hypercholesterolemia indicates the need to assess long-term cost-effectiveness of
      health care programs in patients with this disorder.

PMID- 18060378
TI  - Both aluminum and polyphenols in green tea decoction (Camellia sinensis) affect
      iron status and hematological parameters in rats.
AB  - BACKGROUND: Green tea leaves naturally contain high levels of polyphenols and
      aluminum (Al). Polyphenols in green tea decoction are considered to be one of the
      major factors responsible of low iron status. However, the effects of Al from
      green tea decoction on iron status and hematological parameters remained unclear.
      AIM OF THE STUDY: The objective was to investigate the Al absorption from green
      tea decoction and studied its influence on iron status and hematological
      parameters in rats. METHODS: During the experiment period, rats were given the
      experimental diet + a simple dose of Al sulfate with or without graded doses of
      green tea decoction (25, 50 and 100 g/l). The Al absorption was evaluated in the
      serum; however, iron status was evaluated by the iron concentration in the liver,
      kidney, spleen and femur. In addition, the hemoglobin and hematocrit were
      evaluated. RESULTS: Our results showed that the serum Al significantly increased
      between 61.5 and 342%, as tea doses-dependant. The Al sulfate significantly
      decreased the reserve of iron in all studied organs between 21.7 and 17% (P <
      0.05). In groups receiving green tea decoction alone or Al + graded doses of tea,
      the reserve of iron significantly decreased in all studied organs between 59.4
      and 18.5% (P < 0.01). Al alone or associated with drinking doses of tea
      significantly decreased hemoglobin concentration between 23.6 and 9% (P < 0.05)
      and hematocrit between 12.7 and 7% (P < 0.01). CONCLUSION: Our data showed that
      Al from green tea decoction was more absorbed in the serum than Al sulfate. Al
      absorption was associated with low iron status and reduction of hemoglobin and
      hematocrit. Considering that Al competes with iron in different stage of
      erythropoiesis including transferrin binding, so we could assume that the
      negative effect of tea on iron status arises not only from polyphenols iron
      complexes but also from Al released in tea decoction.

PMID- 18060379
TI  - [Trigeminocardiac reflex in pituitary surgery. A prospective pilot study].
AB  - BACKGROUND: The trigeminocardiac reflex (TCR) is a relatively recently described
      brainstem reflex in the fields of neurosurgery which leads to a simultaneous drop
      in mean arterial pressure (MAP) and heart rate of at least 20% from baseline
      levels after stimulation of a sensible branch of the trigeminal nerve. PATIENTS
      AND METHODS: The purpose of this study was to register prospectively for the
      first time the rate of TCR during trans-sphenoidal surgery and to describe
      possible predispositional factors. This was examined by determining selected
      biomarkers thought to correlate with possible intraoperative ischemic events
      after occurrence of TCR and furthermore with neuroprotective mechanisms
      ("ischemic tolerance"). RESULTS: Three of the 40 patients included (7.5%)
      demonstrated intraoperative occurrence of TCR after exposure of the cavernous
      sinus. One (2.5%) demonstrated a TCR during preparation of the nasal mucosa.
      Permanent cardiovascular damage or unfavorable postoperative outcome through the
      appearance of TCR was not found. There was a trend to lower C-reactive protein
      levels after occurrence of TCR (32 mg/dl vs 14 mg/dl) following normal values
      before operations in all cases. Considering that no clinical clue of ischemia was
      detected, this could mean that some neuroprotective cascades are initiated. There
      was a correlation between tumor necrosis factor A and noradrenalin levels with
      the size (invasivity) of the pituitary adenoma. The administration of atropine
      was necessary in only one patient with intraoperative occurrence of TCR.
      CONCLUSION: On the basis of this study, it cannot be said to what extent
      neuroprotective mechanisms after TCR are activated, but a trend is still
      apparent. Considering the adverse effects and the reflex arc, prophylactic or
      therapeutic treatment with atropine is not justified.

PMID- 18060380
TI  - Continuous Glucose Monitoring System in children with type 1 diabetes mellitus: a
      systematic review and meta-analysis.
AB  - AIMS/HYPOTHESIS: We investigated the potential effects of the Continuous Glucose
      Monitoring System (CGMS), as compared with self-monitoring of blood glucose, on
      glycaemic control in children with type 1 diabetes. METHODS: The following
      electronic databases were searched throughout June 2007: MEDLINE, EMBASE and The
      Cochrane Library. Additional references were obtained from reviewed articles.
      Only randomised controlled trials were included. RESULTS: We included five trials
      involving 131 type 1 diabetic patients in the study. Combined data from all
      trials showed that the CGMS did not significantly reduce HbA1c levels compared
      with control groups. The pooled weighted mean difference was -0.02% (95% CI -0.29
      to 0.25) with a fixed model and remained insignificant in the random effect
      model. Sensitivity analysis determined that the findings were stable. There was a
      trend towards a longer time under the CGMS curve for glucose <3.89 mmol/l in the
      CGMS group compared with the control group (mean difference 49.00 min, 95% CI 
      18.00 to 116.00). The CGMS significantly increased the number of insulin dose
      changes per patient per month for those managed with CGMS compared with the
      control groups (mean difference 6.3 changes, 95% CI 2.88-9.72).
      CONCLUSIONS/INTERPRETATION: The Continuous Glucose Monitoring System is not
      better than self-monitoring of blood glucose with regard to improvement of
      metabolic control among type 1 diabetic children. However, due to the small
      number of participants and methodological limitations of the studies included,
      findings of this meta-analysis should be interpreted with caution.

PMID- 18060381
TI  - Inhibition or deletion of the lipopolysaccharide receptor Toll-like receptor-4
      confers partial protection against lipid-induced insulin resistance in rodent
      skeletal muscle.
AB  - AIMS/HYPOTHESIS: A role for increased activity of the innate immune system in the
      pathogenesis of insulin resistance is supported by a number of studies. The
      current study assessed the potential role of the lipopolysaccharide receptor
      known as Toll-like receptor-4 (TLR-4), a component of the innate immune system,
      in mediating lipid-induced insulin resistance in skeletal muscle. METHODS: The
      effects of TLR-4 inhibition/deletion on lipid-induced insulin resistance was
      determined in skeletal muscle of TLR-4 null mice in vivo and in rat L6 myotubes
      in vitro. RESULTS: In mice, acute hyperlipidaemia induced skeletal muscle insulin
      resistance, but a deletion of TLR-4 conferred significant protection against
      these effects. In L6 myotubes, inhibition of TLR-4 activity substantially reduced
      the capacity of the saturated fatty acid palmitate to induce insulin resistance.
      Importantly, palmitate activated the nuclear factor kappaB (NFkappaB) pathway in
      L6 myotubes and mouse skeletal muscle, and these effects were blocked by
      inhibition of TLR-4 in L6 myotubes and absence of TLR-4 in skeletal muscle.
      Furthermore, inhibition of the NFkappaB pathway downstream of TLR-4 in L6
      myotubes also protected against the induction of insulin resistance by palmitate.
      CONCLUSIONS/INTERPRETATION: Inhibition or absence of TLR-4 confers protection
      against the detrimental effects of lipids on skeletal muscle insulin action, and
      these effects are associated with a prevention of the activation of the NFkappaB
      pathway by lipids. Importantly, inhibition of the NFkappaB pathway in myotubes
      downstream of TLR-4 also protects against lipid-induced insulin resistance,
      suggesting a mechanism by which reduced TLR-4 activity confers beneficial effects
      on insulin action.

PMID- 18060382
TI  - The effect of hypoxemic resuscitation from hemorrhagic shock on blood pressure
      restoration and on oxidative and inflammatory responses.
AB  - OBJECTIVE: We investigated whether hypoxemic resuscitation from hemorrhagic shock
      prevents the late circulatory instability and attenuates the oxidative and
      inflammatory responses associated with the standard strategy. DESIGN AND SETTING:
      Prospective, randomized, controlled animal study in an experimental laboratory of
      a university intensive care unit. SUBJECTS: Thirty-one New Zealand white rabbits
      weighting 3.1-3.4 kg INTERVENTIONS: Anesthetized animals were subjected to
      hemorrhagic shock by exsanguinations to a mean arterial pressure of 40 mmHg for
      60 min. Resuscitation was performed by reinfusing the shed blood for 30 min under
      normoxemia (PaO(2) 95-105 mmHg, control group, n=10) or hypoxemia (PaO(2) 35-40
      mmHg, hypox-res group, n=10); Ringer's lactate was given from 30 to 60 min to
      restore arterial pressure within baseline values. A sham group was assigned
      (n=11). Animals were recorded for 120 min postresuscitation and for further 360
      min to assess the early mortality rate. MEASUREMENTS AND RESULTS: Hypoxemic
      resuscitation compared with normoxemic resuscitation from hemorrhagic shock was
      associated with (a) a better hemodynamic condition assessed by the gradual
      restoration of blood pressure, higher urinary output associated with less fluid
      infusion; (b) lower reactive oxygen species production assessed by the reduced
      blood geometric mean fluorescence intensity, lower malondialdehyde, and higher
      ratio of reduced to total glutathione levels; (c) attenuation in the plasma
      concentrations of IL-1beta, TNF-alpha, and IL-6; and (d) no difference in
      mortality rate. CONCLUSIONS: Hypoxemic resuscitation from hemorrhagic shock is
      more efficient than normoxemic in restoring the blood pressure and in attenuating
      the excessive oxidative and inflammatory responses observed during normoxemic
      resuscitation.

PMID- 18060383
TI  - The role of PCL reconstruction in knees with combined PCL and posterolateral
      corner deficiency.
AB  - Although many PCL injuries are in combination with posterolateral corner (PLC)
      injuries, there has been little work done on combined injury reconstruction; the
      literature includes differing recommendations. It was hypothesised that a double
      bundle PCL reconstruction would restore both posterior drawer and external
      rotation laxities closer to normal than an isolated single-bundle reconstruction
      in combined PCL plus PLC-deficient knees. However, it was also hypothesised that
      an isolated PCL reconstruction would still leave abnormal rotation laxity. In
      this controlled laboratory study, cadaver knee kinematics were measured
      electromagnetically with posterior drawer, external rotation, varus rotation
      loads applied, at sequential stages: intact; PCL-deficient; PCL plus PLC
      deficient; double-bundle PCL reconstruction; single-bundle PCL reconstruction.
      The grafts were tensed using a posterior drawer laxity matching protocol. There
      was no significant difference between single- and double-bundle PCL
      reconstructions at any angle of flexion: both reconstructions restored posterior
      drawer to normal; neither reconstruction restored external rotation or varus
      laxity to normal. We concluded that, in combined PCL plus PLC deficiency,
      isolated PCL reconstruction only controls tibial posterior drawer, but is not
      sufficient to restore rotational laxity to normal. Double-bundle PCL
      reconstruction was not better than single-bundle, so the added complexity of
      double-bundle reconstruction does not seem to be justified by these results.

PMID- 18060384
TI  - Diverse endophytic nitrogen-fixing bacteria isolated from wild rice Oryza
      rufipogon and description of Phytobacter diazotrophicus gen. nov. sp. nov.
AB  - Twenty-three nitrogen-fixing bacteria were isolated from surface-sterilized stems
      and roots of wild rice Oryza rufipogon. Four clusters were defined among these
      bacteria by SDS-PAGE protein patterns and further confirmed by IS-PCR finger
      printing analysis. Phylogenetic analysis of 16S rRNA gene sequences showed that
      the representative strains LS 8 and LS 18 of cluster II formed a monophyletic
      group sharing 94.0-97.3% similarities with defined enterobacterial species within
      the genera Salmonella, Citrobacter, Pantoea, Klebsiella, and Enterobacter. DNA
      DNA hybridization, physiological, biochemical tests, and cell morphology also
      revealed that these strains could be differentiated from the related
      enterobacterial species. Based upon these results, we propose Phytobacter
      diazotrophicus gen. nov., sp. nov. to the bacterial group represented by strains
      LS 8 and LS 18. The type strain is LS 8(T) (=DSM 17806(T) = LMG 23328(T) = CGMCC
      1.5339(T)). The DNA G+C content of strain LS 8(T) is 58.6 +/- 0.5 mol%.

PMID- 18060385
TI  - Curcumin attenuates indomethacin-induced oxidative stress and mitochondrial
      dysfunction.
AB  - Oxidative stress and mitochondrial dysfunction have been implicated in the
      pathogenesis of indomethacin-induced enteropathy. We evaluated the potential of
      curcumin, a known cytoprotectant, as an agent to protect against such effects.
      Rats were pretreated with curcumin (40 mg/kg by intra-peritoneal injection)
      before administration of indomethacin (20 mg/kg by gavage). One hour later, the
      small intestine was isolated and used for assessment of parameters of oxidative
      stress. Mitochondria, brush border membranes (BBM) and surfactant-like particles
      (SLP) were also isolated from the tissue. Mitochondria were used for assessment
      of functional integrity, estimation of products of lipid peroxidation and lipid
      content. BBM were used for estimation of products of lipid peroxidation and lipid
      content, while the SLP were used for measurement of lipid content. The results
      showed that oxidative stress and mitochondrial dysfunction occurred in the small
      intestine of indomethacin-treated rats. Pre-treatment with curcumin was found to
      ameliorate these drug-induced changes. Significant changes were seen in some of
      the lipids in the mitochondria, BBM and SLP in response to indomethacin. However,
      curcumin did not have any significant effect on these drug-induced changes. We
      conclude that curcumin, by attenuating oxidative stress and mitochondrial
      dysfunction, holds promise as an agent that can potentially reduce NSAID-induced
      adverse effects in the small intestine.

PMID- 18060386
TI  - In vivo electrophysiological assessment of the putative antidepressant Wf-516 in
      the rat raphe dorsalis, locus coeruleus and hippocampus.
AB  - Wf-516 is a potential novel antidepressant. It has high affinity for serotonin (5
      hydroxytryptamine; 5-HT) transporters, 5-HT(1A) and 5-HT(2A) receptors. In the
      present study, the pharmacologic properties of Wf-516 were thus assessed using in
      vivo electrophysiology in the rat dorsal raphe nucleus (DRN), locus coeruleus
      (LC) and hippocampus. Glass microelectrodes were lowered into the DRN, LC or
      hippocampus, and neurons were recorded and tested using systemic or
      microiontophoretic injections of drugs. In the DRN, cumulative doses of 0.5 mg/kg
      of Wf-516 were injected intravenously and total inhibition of 5-HT neurons firing
      was obtained with 2.8 +/- 0.3 mg/kg. The administration of 1 mg/kg of Wf-516,
      which by itself did not induce a change in the firing of 5-HT neurons, markedly
      attenuated the inhibitory effect of the 5-HT(1A) autoreceptor agonist LSD,
      indicating that Wf-516 is a 5-HT(1A) autoreceptor antagonist. In the LC, 1 mg/kg
      of Wf-516 dampened the inhibitory effect of the preferential 5-HT(2A) agonist DOI
      on norepinephrine (NE) neurons, indicating that Wf-516 is also a 5-HT(2A)
      receptor antagonist. In the hippocampus, cumulative intravenous doses of Wf-516
      significantly increased the recovery time of firing activity of CA(3) pyramidal
      neurons after 5-HT applications, indicating an inhibitory effect on 5-HT
      reuptake. Unlike the 5-HT(1A) antagonist WAY100635, Wf-516 did not block the
      inhibitory effect of microiontophoretic application of 5-HT, indicating that this
      drug is devoid of 5-HT(1A) receptor antagonistic activity in this postsynaptic
      structure. These properties of WF-516 define the transporter/receptorial profile
      of an antidepressant with superior effectiveness.

PMID- 18060388
TI  - A picture is worth a thousand words: animations and simulations in the teaching
      of analytical science.

PMID- 18060387
TI  - Behavioral and neurochemical characterization of mice deficient in the
      phosphodiesterase-4B (PDE4B) enzyme.
AB  - RATIONALE: Phosphodiesterases (PDEs) belonging to the PDE4 family control
      intracellular concentrations of cyclic adenosine monophosphate (cAMP) by
      catalyzing its hydrolysis. Four separate PDE4 genes (PDE4A, PDE4B, PDE4C, and
      PDE4D) have been identified. PDE4 has been reported to be involved in various
      central nervous system (CNS) functions including depression, memory, and
      schizophrenia, although the specific subtype mediating these effects remains
      unclear. OBJECTIVE: To investigate the role of PDE4B in the CNS, PDE4B wild-type
      and knockout mice (C57BL/6N background) were assessed in a variety of well
      characterized behavioral tasks, and their brains were assayed for monoamine
      content. RESULTS: Knockout mice showed a significant reduction in prepulse
      inhibition. Spontaneous locomotor activity was decreased (16%) in knockout mice.
      Furthermore, when challenged with amphetamine, both groups of mice responded
      similarly to a low dose of d-amphetamine (1.0 mg/kg), but knockout mice showed an
      enhanced response to a higher dose (1.78 mg/kg). Decreases in baseline levels of
      monoamines and their metabolites within the striatum of knockout mice were also
      observed. PDE4B knockout mice showed a modest decrease in immobility time in the
      forced swim test that approached significance. In several other tests, including
      the elevated plus maze, hot plate, passive avoidance, and Morris water maze, wild
      type and knockout mice performed similarly. CONCLUSION: The present studies
      demonstrate decreased striatal DA and 5-HT activity in the PDE4B knockout mice
      associated with decreased prepulse inhibition, decreased baseline motor activity,
      and an exaggerated locomotor response to amphetamine. These data further support
      a role for PDE4B in psychiatric diseases and striatal function.

PMID- 18060389
TI  - An amperometric hydrogen peroxide biosensor based on immobilization of
      horseradish peroxidase on an electrode modified with magnetic dextran
      microspheres.
AB  - A new kind of magnetic dextran microsphere (MDMS) with uniform shape and narrow
      diameter distribution has been prepared from magnetic iron nanoparticles and
      dextran. Horseradish peroxidase (HRP) was successfully immobilized on the surface
      of an MDMS-modified glassy-carbon electrode (GCE), and the immobilized HRP
      displayed excellent electrocatalytic activity in the reduction of H(2)O(2) in the
      presence of the mediator hydroquinone (HQ). The effects of experimental variables
      such as the concentration of HQ, solution pH, and the working potential were
      investigated for optimum analytical performance. This biosensor had a fast
      response to H(2)O(2) of less than 10 s and an excellent linear relationship was
      obtained in the concentration range 0.20 micromol L(-1)-0.68 mmol L(-1), with a
      detection limit of 0.078 micromol L(-1) (S/N = 3) under the optimum conditions.
      The response showed Michaelis-Menten behavior at larger H(2)O(2) concentrations,
      and the apparent Michaelis-Menten constant K(M)(app) was estimated to be 1.38
      mmol L(-1). Moreover, the selectivity, stability, and reproducibility of the
      biosensor were evaluated, with satisfactory results.

PMID- 18060390
TI  - High-throughput determination of pesticide residues in food commodities by use of
      ultra-performance liquid chromatography-tandem mass spectrometry.
AB  - A rapid, simple, and sensitive multiresidue method for analysis of 53 pesticides
      in fruit and vegetables by ultra-performance liquid chromatography (UPLC) coupled
      to triple-quadrupole tandem mass spectrometry (MS-MS) has been developed and
      validated. Prior to analysis, analytes were extracted by use of buffered QuEChERS
      (quick, easy, cheap, effective, rugged, safe) methodology without further cleanup
      for non fatty matrices. Chromatographic conditions were optimised in order to
      achieve a fast separation in multiple reaction monitoring (MRM) mode. Indeed,
      more than 50 pesticides can be separated in less then 10 min. Four common
      representative matrices (cucumber, orange, strawberry, and olive) were selected
      to investigate the effect of different matrices on recovery and precision. Mean
      recoveries ranged from 70 to 109% with relative standard deviations lower than
      20% for all the pesticides assayed in the four selected matrices. The method has
      been applied to the analysis of 200 vegetable samples, and imidacloprid was the
      pesticide most frequently found, with concentrations ranging from 0.01 to 1.00 mg
      kg(-1). This methodology combines the advantages of both QuEChERS and UPLC-MS-MS
      producing a very rapid, sensitive, and reliable procedure which can be applied in
      routine analytical laboratories.

PMID- 18060391
TI  - A catalytic adsorptive stripping voltammetric procedure for trace determination
      of Cr(VI) in natural samples containing high concentrations of humic substances.
AB  - A simple and fast catalytic adsorptive stripping voltammetric procedure for trace
      determination of Cr(VI) in natural samples containing high concentrations of
      humic substances has been developed. The procedure for chromium determination in
      the presence of DTPA and nitrates was employed as the initial method. In order to
      enhance the selectivity vs. Cr(III) the measurements were performed at 40 degrees
      C. Interference from dissolved organic matter such as humic and fulvic acids was
      drastically decreased by adding Amberlite XAD-7 resin to the voltammetric cell
      before the deaeration step. The whole procedure was applied to a single cell,
      which allowed monitoring of the voltammetric scan. Optimum conditions for
      removing humic and fulvic acids due to their adsorption on XAD-7 resin were
      evaluated. The use of XAD-7 resin also minimize interferences from various
      cationic, anionic, and nonionic surfactants. The calibration graph for Cr(VI) for
      an accumulation time of 30 s was linear in the range 5 x 10(-10) to 5 x 10(-8)
      mol L(-1). The relative standard deviation for determination of Cr(VI) at a
      concentration of 1 x 10(-8) mol L(-1) was 3.5% (n = 5). The detection limit
      estimated from 3 times the standard deviation for low Cr(VI) concentrations and
      an accumulation time of 30 s was about 1.3 x 10(-10) mol L(-1). The proposed
      method was successfully applied to Cr(VI) determination at trace levels in soil
      samples.

PMID- 18060392
TI  - Electrogeneration of polyluminol and chemiluminescence for new disposable
      reagentless optical sensors.
AB  - A performant reagentless electrochemiluminescent (ECL) detection system for
      H(2)O(2) is presented, based on an electropolymerized polyluminol film prepared
      under near-neutral conditions. Such an original polyluminol electrodeposition is
      reported for the first time and on a screen-printed electrode (SPE) surface.
      Electropolymerized luminol acts as an active luminophore of the
      electrochemiluminescent reaction, as the monomer does. Polymerization conditions
      have been optimized in order to obtain the best ECL responses to H(2)O(2). By
      performing electrodeposition in a potentiostatic mode, at 425 mV vs. Ag|AgCl, in
      0.1 mol L(-1) phosphate/0.1 mol L(-1) KCl pH 6 and 1 mmol L(-1) luminol, with a
      total charge of 0.5 mC, the linear range for H(2)O(2) detection extends from 7.9
      x 10(-8) mol L(-1) to 1.3 x 10(-3) mol L(-1). Such performant disposable
      reagentless easy-to-use miniaturized systems based on SPEs should be applicable
      to the electrochemiluminescent detection of many oxidase-substrate compounds.

PMID- 18060393
TI  - Stable isotope dilution assays in mycotoxin analysis.
AB  - The principle and applications of stable isotope dilution assays (SIDAs) in
      mycotoxin analysis are critically reviewed. The general section includes
      historical aspects of SIDAs, the prerequisites and limitations of the use of
      stable isotopically labelled internal standards, and possible calibration
      procedures. In the application section actual SIDAs for the analysis of
      trichothecenes, zearalenone, fumonisins, patulin, and ochratoxin A are presented.
      The syntheses and availability of labelled mycotoxins for use as internal
      standards is reviewed and specific advances in food analysis and toxicology are
      demonstrated. The review indicates that LC-MS applications, in particular,
      require the use of stable isotopically labelled standards to compensate for
      losses during clean-up and for discrimination due to ion suppression. As the
      commercial availability of these compounds continues to increase, SIDAs can be
      expected to find expanding use in mycotoxin analysis.

PMID- 18060394
TI  - Study of traffic-emitted lead pollution of soil and plants using different fuzzy
      clustering algorithms.
AB  - We discuss the clustering of 234 environmental samples resulting from an
      extensive monitoring program concerning soil lead content, plant lead content,
      traffic density, and distance from the road at different sampling locations in
      former East Germany. Considering the structure of data and the unsatisfactory
      results obtained applying classical clustering and principal component analysis,
      it appeared evident that fuzzy clustering could be one of the best solutions. In
      the following order we used different fuzzy clustering algorithms, namely, the
      fuzzy c-means (FCM) algorithm, the Gustafson-Kessel (GK) algorithm, which may
      detect clusters of ellipsoidal shapes in data by introducing an adaptive distance
      norm for each cluster, and the fuzzy c-varieties (FCV) algorithm, which was
      developed for recognition of r-dimensional linear varieties in high-dimensional
      data (lines, planes or hyperplanes). Fuzzy clustering with convex combination of
      point prototypes and different multidimensional linear prototypes is also
      discussed and applied for the first time in analytical chemistry
      (environmetrics). The results obtained in this study show the advantages of the
      FCV and GK algorithms over the FCM algorithm. The performance of each algorithm
      is illustrated by graphs and evaluated by the values of some conventional cluster
      validity indices. The values of the validity indices are in very good agreement
      with the quality of the clustering results.

PMID- 18060395
TI  - fMRI reliability in subjects with stroke.
AB  - Functional MRI (fMRI) has become one of the most commonly used neuroimaging tools
      to assess the cortical effects associated with rehabilitation, learning, or
      disease recovery in subjects with stroke. Despite this, there has been no
      systematic study of the reliability of the fMR signal in this population. The
      purpose of this study was to examine the within- and between-session reliability
      of fMRI in cortical and cerebellar structures in subjects with stroke during a
      complex, continuous visual motor task performed with the less affected hand. Nine
      subjects with stroke underwent four testing trials during two sessions separated
      by three weeks. Subjects performed a drawing task using an MRI compatible
      joystick while in the MRI. Methods of analysis evaluated included: percent signal
      intensity change, active voxel count and a voxel by voxel stat value analysis
      within and between testing sessions. Reliability was determined with Interclass
      correlation coefficients (ICC) in the following regions of interest: primary
      motor (M1), primary sensory (S1), premotor cortex (PMC), medial cerebellum (MCB),
      and lateral cerebellum (LCB). Results indicate that intensity change has superior
      reliability to the other methods of analysis (Average ICC across brain regions
      and trials: intensity change: 0.73, voxel count: 0.58, voxel by voxel: 0.67) and
      that generally with any analysis method, within-session reliability was higher
      than between-session, as indicated by higher ICC values across brain regions.
      Overall, when comparing between-session results, moderate to good reliability was
      obtained with intensity change (ICC: M1: 0.52, S1: 0.80, SMA: 0.78, PMC: 0.94,
      MCB: 0.86, and LCB: 0.59). These results show good reliability in subjects with
      stroke when performing a continuous motor task. These findings give confidence
      for interpreting fMRI test/retest research in subjects with stroke.

PMID- 18060396
TI  - Prior outpatient antibiotic use as predictor for microbial aetiology of community
      acquired pneumonia: hospital-based study.
AB  - OBJECTIVE: The causative micro-organism in community-acquired pneumonia (CAP) is
      often difficult to predict. Different studies have examined chronic morbidity and
      clinical symptoms as predictors for microbial aetiology of pneumonia. The aim of
      our study was to assess whether prior outpatient antimicrobial treatment is
      predictive for determining the microbial aetiology of CAP. METHODS: This was a
      hospital-based prospective observational study including all patients admitted
      with CAP between 1 October 2004 and 1 August 2006. Microbial investigations
      included sputum, blood culture, sputum PCR, antigen testing and serology.
      Exposure to antimicrobial drugs prior to hospital admission was ascertained
      through community pharmacy dispensing records. Multivariate logistic regression
      analysis was conducted to assess whether prior outpatient antimicrobial treatment
      is a predictor of microbial aetiology. Patient demographics, co-morbidities and
      pneumonia severity were considered to be other potential predictors. RESULTS:
      Overall, 201 patients were included in the study. The microbial aetiology was
      determined in 64% of the patients. The five most prevalent pathogens were
      Streptococcus pneumoniae, Heamophilus influenzae, Legionella spp., Mycoplasma
      pneumoniae and Influenza virus A+B. Forty-seven of the patients (23%) had
      received initial antimicrobial treatment as outpatients. Multivariate analyses
      revealed that initial outpatient beta-lactam treatment was associated with a
      threefold increased chance of finding atypical pathogens and a threefold
      decreased probability of pneumococcal infection; the corresponding odds ratios
      were 3.51 (95% CI 1.25-9.99) and 0.30 (95% CI 0.10-0.90), respectively. Patients
      who received macrolides prior to hospitalisation had an increased probability of
      viral pneumonia. CONCLUSION: Prior outpatient antimicrobial therapy has a
      predictive value in the diagnostic workup aimed at identifying the causative
      pathogen and planning corresponding antimicrobial treatment in patients
      hospitalised for pneumonia.

PMID- 18060397
TI  - Intracecal fetiform teratoma.
AB  - Fetiform teratoma is a rare form of mature cystic teratoma that is highly
      developed and organized, resembling a fetus-like structure. These are rare
      entities that have been typically described in women of reproductive age and most
      often present as ovarian masses. Only two cases of a fetiform teratoma have been
      reported in a male. Although teratomas are a common benign entity, only five
      prior cases of teratoma involving the cecum have been described. We present an
      atypical case of an intracecal fetiform teratoma occurring in a 2(1/2)-year-old
      Chinese boy.

PMID- 18060398
TI  - Isolated fallopian tube torsion: sonographic and CT features.
AB  - BACKGROUND: Isolated fallopian tube torsion (IFTT) rarely occurs in pediatric
      patients and is difficult to diagnose preoperatively. OBJECTIVE: To determine the
      common sonographic and CT findings in girls with IFTT. MATERIALS AND METHODS: We
      retrospectively reviewed the hospital charts and imaging studies of the eight
      girls diagnosed with and treated for IFTT at Columbus Children's Hospital between
      January 1995 and June 2006 whose final diagnosis was IFTT. RESULTS: The mean age
      was 13 years with a range of 12 to 15 years. Two girls were premenarcheal. The
      most common presenting symptom was acute pelvic pain (n = 5). All patients were
      imaged. Six girls were imaged first with US, and the most common finding was a
      complex cystic pelvic mass in the midline (n = 5) and normal uterus and ovaries.
      Three of the eight girls had imaging with CT. In two girls, the torsed tube could
      be identified. In 63% of the girls, the uterus was deviated toward the side of
      torsion. The correct preoperative diagnosis was made in only one girl. None of
      the torsed fallopian tubes was salvaged at surgery. Pathological findings
      included ipsilateral adnexal cysts associated with the torsed tube (n = 7).
      CONCLUSION: IFTT should be considered in the differential diagnosis for
      perimenarcheal girls who present with acute pelvic pain and who demonstrate a
      cystic mass in a midline position (either in the cul-de-sac or superior to the
      uterus) associated with a normal ipsilateral ovary.

PMID- 18060399
TI  - Lycopene over-accumulation by disruption of the negative regulator gene crgA in
      Mucor circinelloides.
AB  - Lycopene has become one of the most interesting antioxidant compounds, especially
      in relation to human health. This work describes a genetic strategy to modify the
      carotenoid biosynthesis pathway to develop a lycopene-overproducing strain. The
      crgA gene, a negative regulator of carotenogenesis, was disrupted in the Mucor
      circinelloides strain MU202, which lacks the lycopene cyclase activity and
      accumulates lycopene instead of beta-carotene. The resultant strain, MU224,
      demonstrated increased transcriptional levels of the carotenogenesis structural
      genes carRP and carB compared to the parental strain MU202. As a consequence,
      strain MU224 accumulated 5 mg/g of dry weight of cells in liquid cultures, a
      sevenfold increase with respect to the parental strain. Moreover, when lycopene
      production was examined in a complex enriched medium, biomass increased tenfold
      compared to that obtained in synthetic minimal medium. In this complex medium,
      the production rate of lycopene by strain MU224 reached 54 g/l. These results
      illustrate how a combination of genetic manipulation and optimized culture
      conditions can be utilized to enhance the production of commercially desirable
      compounds such as lycopene.

PMID- 18060400
TI  - Substrate specificity of Stenotrophomonas nitritireducens in the hydroxylation of
      unsaturated fatty acid.
AB  - An isolated bacterium that converted unsaturated fatty acids to hydroxy fatty
      acids was identified as Stenotrophomonas nitritireducens by API analysis,
      cellular fatty acids compositions, sequencing the full 16S ribosomal ribonucleic
      acid, and evaluating its nitrite reduction ability. S. nitritireducens has unique
      regio-specificity for C16 and C18 cis-9 unsaturated fatty acids. These fatty
      acids are converted to their 10-hydroxy fatty acids without detectable
      byproducts. Among the cis-9-unsaturated fatty acids, S. nitritireducens showed
      the highest specificity for linoleic acid. The cells converted 20 mM linoleic
      acid to 13.5 mM 10-hydroxy-12(Z)-octadecenoic acid at 30 degrees C and pH 7.5
      with a yield of 67.5% (mol/mol).

PMID- 18060401
TI  - Rates of chilling to 0 degrees C: implications for the survival of microorganisms
      and relationship with membrane fluidity modifications.
AB  - The effects of slow chilling (2 degrees C min(-1)) and rapid chilling (2,000
      degrees C min(-1)) were investigated on the survival and membrane fluidity of
      Escherichia coli, of Bacillus subtilis, and of Saccharomyces cerevisiae. Cell
      death was found to be dependent on the physiological state of cell cultures and
      on the rate of temperature downshift. Slow temperature decrease allowed cell
      stabilization, whereas the rapid chilling induced an immediate loss of viability
      of up to more than 90 and 70% for the exponentially growing cells of E. coli and
      B. subtilis, respectively. To relate the results of viability with changes in
      membrane physical state, membrane anisotropy variation was monitored during
      thermal stress using the fluorescence probe 1,6-diphenyl-1,3,5-hexatriene. No
      variation in the membrane fluidity of all the three microorganisms was found
      after the slow chilling. It is interesting to note that fluorescence measurements
      showed an irreversible rigidification of the membrane of exponentially growing
      cells of E. coli and B. subtilis after the instantaneous cold shock, which was
      not observed with S. cerevisiae. This irreversible effect of the rapid cold shock
      on the membrane correlated well with high rates of cell inactivation. Thus,
      membrane alteration seems to be the principal cause of the cold shock injury.

PMID- 18060402
TI  - Expression of Clostridium acetobutylicum butanol synthetic genes in Escherichia
      coli.
AB  - A recombinant butanol pathway composed of Clostridium acetobutylicum ATCC 824
      genes, thiL, hbd, crt, bcd-etfB-etfA, and adhe1 (or adhe) coding for acetyl-CoA
      acetyltransferase (THL), beta-hydroxybutyryl-CoA dehydrogenase (HBD), 3
      hydroxybutyryl-CoA dehydratase (CRT), butyryl-CoA dehydrogenase (BCD),
      butyraldehyde dehydrogenase (BYDH), and butanol dehydrogenase (BDH), under the
      tac promoter control was constructed and was introduced into Escherichia coli.
      The functional expression of these six enzymes was proved by demonstrating the
      corresponding enzyme activities using spectrophotometric, high performance liquid
      chromatography and gas chromatography analyses. The BCD activity, which was not
      detected in E. coli previously, was shown in the present study by performing the
      procedure from cell extract preparation to activity measurement under anaerobic
      condition. Moreover, the etfA and etfB co-expression was found to be essential
      for the BCD activity. In the case of BYDH activity, the adhe gene product was
      shown to have higher specificity towards butyryl-CoA compared to the adhe1
      product. Butanol production from glucose was achieved by the highly concentrated
      cells of the butanologenic E. coli strains, BUT1 with adhe1 and BUT2 with adhe,
      under anaerobic condition, and the BUT1 and BUT2 strains were shown to produce 4
      and 16-mM butanol with 6- and 1-mM butyrate as a byproduct, respectively. This
      study reports the novel butanol production by an aerobically pregrown
      microorganism possessing the genes of a strict anaerobe, Clostridium
      acetobutylicum.

PMID- 18060403
TI  - Immune modulation by melanoma and ovarian tumor cells through expression of the
      immunosuppressive molecule CD200.
AB  - BACKGROUND AND OBJECTIVE: Immune escape by tumors can occur by multiple
      mechanisms, each a significant barrier to immunotherapy. We previously
      demonstrated that upregulation of the immunosuppressive molecule CD200 on chronic
      lymphocytic leukemia cells inhibits Th1 cytokine production required for an
      effective cytotoxic T cell response. CD200 expression on human tumor cells in
      animal models prevents human lymphocytes from rejecting the tumor; treatment with
      an antagonistic anti-CD200 antibody restored lymphocyte-mediated tumor growth
      inhibition. The current study evaluated CD200 expression on solid cancers, and
      its effect on immune response in vitro. METHODS AND RESULTS: CD200 protein was
      expressed on the surface of 5/8 ovarian cancer, 2/4 melanoma, 2/2 neuroblastoma
      and 2/3 renal carcinoma cell lines tested, but CD200 was absent on prostate,
      lung, breast, astrocytoma, or glioblastoma cell lines. Evaluation of patient
      samples by immunohistochemistry showed strong, membrane-associated CD200 staining
      on malignant cells of melanoma (4/4), ovarian cancer (3/3) and clear cell renal
      cell carcinoma (ccRCC) (2/3), but also on normal ovary and kidney. CD200
      expression on melanoma metastases was determined by RT-QPCR, and was found to be
      significantly higher in jejunum metastases (2/2) and lung metastases (2/6) than
      in normal samples. Addition of CD200-expressing, but not CD200-negative solid
      tumor cell lines to mixed lymphocyte reactions downregulated the production of
      Th1 cytokines. Inclusion of antagonistic anti-CD200 antibody restored Th1
      cytokine responses. CONCLUSION: These data suggest that melanoma, ccRCC and
      ovarian tumor cells can express CD200, thereby potentially suppressing anti-tumor
      immune responses. CD200 blockade with an antagonistic antibody may permit an
      effective anti-tumor immune response in these solid tumor types.

PMID- 18060404
TI  - Vaccination of colorectal cancer patients with TroVax given alongside
      chemotherapy (5-fluorouracil, leukovorin and irinotecan) is safe and induces
      potent immune responses.
AB  - Modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax) has been
      evaluated in an open label phase II study in metastatic colorectal cancer
      patients. The primary objective was to assess the safety and immunogenicity of
      TroVax injected before, during and after treatment with 5-fluorouracil,
      leukovorin and irinotecan. TroVax was administered to 19 patients with metastatic
      colorectal cancer. Twelve patients had blood samples taken following each of the
      six injections and were considered to be evaluable for assessment of
      immunological responses. Both antibody and cellular responses specific for the
      tumor antigen 5T4 and the viral vector MVA were monitored throughout the study.
      Administration of TroVax alongside chemotherapy was safe and well tolerated with
      no SAEs attributed to the vaccine and no enhancement of chemo-related toxicity.
      Of the 12 patients who were evaluable for assessment of immune responses, ten
      mounted 5T4-specific antibody responses with titers ranging from 10 to > 5,000.
      IFNgamma ELISPOT responses specific for 5T4 were detected in 11 patients with
      frequencies exceeding one in 1,000 PBMCs in five patients. Eight patients
      presented with elevated circulating CEA concentrations, six of whom showed
      decreases in excess of 50% during chemotherapy and four had CEA levels which
      remained stable for > 1 month following completion of chemotherapy. Of the 19
      intention to treat (ITT) patients, one had a CR, six had PRs and five had SD.
      Potent 5T4-specific cellular and/or humoral immune responses were induced in all
      12 evaluable patients and were detectable in most patients during the period in
      which chemotherapy was administered. These data demonstrate that TroVax can be
      layered on top of chemotherapy regimens without any evidence of enhanced toxicity
      or reduced immunological or therapeutic efficacy.

PMID- 18060405
TI  - Hallmarks of RNA silencing are found in the smut fungus Ustilago hordei but not
      in its close relative Ustilago maydis.
AB  - RNA interference (RNAi) acts through transcriptional and post-transcriptional
      gene silencing of homologous sequences. With the goal of using RNAi as a tool for
      studying gene function in the related basidiomycete cereal pathogens Ustilago
      hordei and Ustilago maydis, we developed a general purpose RNAi expression
      vector. Tandem, inverted fragments of the GUS gene were inserted into this vector
      flanking an intron and used to transform engineered GUS-expressing haploid cells.
      Down-regulation of the GUS gene and production of siRNAs were seen only in U.
      hordei, even though corresponding GUS double-stranded RNA was detected in both
      species. Similarly, when the endogenous bW mating-type gene was targeted by RNAi,
      mating was reduced only in U. hordei. Our work demonstrates the feasibility of
      using RNAi in U. hordei and provides experimental support for the observed lack
      of RNAi components in the U. maydis genome. We hypothesize that the sharply
      limited transposon complement in U. maydis is a biological consequence of this
      absence.

PMID- 18060407
TI  - Importance of co-cultivation medium pH for successful Agrobacterium-mediated
      transformation of Lilium x formolongi.
AB  - An efficient system for Agrobacterium-mediated transformation of Lilium x
      formolongi was established by preventing the drastic drop of pH in the co
      cultivation medium with MES. Meristematic nodular calli were inoculated with an
      overnight culture of A. tumefaciens strain EHA101 containing the plasmid pIG121
      Hm which harbored intron-containing beta-glucuronidase (GUS), hygromycin
      phosphotransferase (HPT), and neomycin phosphotransfease II (NPTII) genes. After
      three days of co-cultivation on 2 g/l gellan gum-solidified MS medium containing
      100 microM acetosyringone, 30 g/l sucrose, 1 mg/l picloram and different
      concentrations of MES, they were cultured on the same medium containing 12.5 mg/l
      meropenem to eliminate Agrobacterium for 2 weeks and then transferred onto medium
      containing the same concentration of meropenem and 25 mg/l hygromycin for
      selecting putative transgenic calli. Transient GUS expression was only observed
      by adding MES to co-cultivation medium. Hygromycin-resistant transgenic calli
      were obtained only when MES was added to the co-cultivation medium especially at
      10 mM. The hygromycin-resistant calli were successfully regenerated into
      plantlets after transferring onto picloram-free medium. Transformation of plants
      was confirmed by histochemical GUS assay, PCR analysis and Southern blot
      analysis.

PMID- 18060408
TI  - Use of 4-methylindole or 7-methyl-DL-tryptophan in a transformant selection
      system based on the feedback-insensitive anthranilate synthase alpha-subunit of
      tobacco (ASA2).
AB  - Effective selectable markers are needed for basic research and commercial
      applications that do not involve antibiotic or herbicide resistance. A novel
      selection system based on a feedback-insensitive anthranilate synthase alpha
      subunit of tobacco (ASA2) as selectable marker using either 4-methylindole (4MI)
      or 7-methyl-DL-tryptophan (7MT) as the selection agent was developed. We found
      that these two components were able to discriminate better between ASA2
      expressing and untransformed lines than the most commonly used analog 5
      methyltryptopan (5MT) in the seedling growth inhibition test. We successfully
      integrated an expression cassette containing an ASA2 cDNA driven by a cauliflower
      mosaic virus 35S promoter into tobacco leaf discs by A. tumefaciens and selected
      transgenic plants on medium supplemented with 300 microM of 7MT or 4MI. Due to
      the expression of the feedback-insensitive ASA2, the transgenic lines produced
      showed higher free tryptophan (Trp) concentrations than the untransformed WT
      control. These results demonstrate the feasibility of the selection system with
      the ASA2 gene in combination with the use of Trp or indole analogs as selective
      agent.

PMID- 18060409
TI  - Flat panel computed tomography for non-invasive flow measurement: initial results
      in in-vitro studies.
AB  - The purpose was to evaluate the feasibility of flat panel computed tomography
      (FPCT) for quantifying flow by analyzing contrast changes along the z-axis in an
      in-vitro setting. Contrast material was injected in a 3-mm silicone tube at flow
      rates of 0.1, 0.2, 0.5 and 1.0 ml/s using a commercially available injector pump.
      FPCT scans of this phantom were performed with a gantry rotation time of 3 s.
      From this data 41 phases were reconstructed at different points in time using a
      full and a partial gantry rotation. The differences in the contrast material
      arrival time and the contrast enhancement along the z-axis were recorded. Flow
      was calculated from this data and compared to the injector settings. There was a
      good agreement between the injector settings and the calculated flow rates, but
      agreement decreased with increasing flow rates. Absolute (percent) mean deviation
      between the injector settings and calculated flow values was 0.0230 +/-
      0.0489ml/s (3.7243 +/- 4.7817%) using the full gantry rotation. Repeated
      measurement ANOVA failed to show significant differences between the various
      techniques (p = 0.9726). FPCT allows for computing flow. While preliminary
      results indicate a good agreement at low flow rates, further studies are needed
      to assess this technique for higher flow rates.

PMID- 18060410
TI  - Using an electrode as a lever to increase the distance between renal cell
      carcinoma and bowel during CT-guided radiofrequency ablation.
AB  - The technique of using an electrode as a lever to increase the distance between
      renal cell carcinoma (RCC) and bowel during CT-guided radiofrequency ablation
      (RFA) is described. CT-guided percutaneous RFA was performed in two patients with
      two RCCs, which were in close proximity to the adjacent bowel. A sterile drape
      was placed on the electrode handle following appropriate electrode placement
      within the tumor in order to displace the kidney upward and to widen the distance
      to >5 mm between RCC and bowel (RCC-to-bowel distance). In patient 1, the RCC-to
      bowel distance increased from 3 mm to 6 mm; in patient 2, from less than 2 mm to
      6 mm. Follow-up CT performed 1 month after RFA demonstrated not only complete
      ablation of the two RCCs but also no thermal injury to the bowel adjacent to the
      tumors. In conclusion, an electrode might be used as a lever to increase RCC-to
      bowel distance during CT-guided RFA by placing a sterile drape on it.

PMID- 18060406
TI  - Early developmental and stress responsive ESTs from mungbean, Vigna radiata (L.)
      Wilczek, seedlings.
AB  - Although mungbean (Vigna radiata (L.) Wilczek) is commonly used as human food;
      the genomic resources of this species available in databases are limited. This
      study aims to develop expressed sequence tag (EST) resources for mungbean genes
      informative to early seedling development and chilling response. Two mungbean
      varieties that differ in disease resistance were found to also differ in their
      susceptibility to chilling temperatures. A total of 1,198 ESTs were obtained from
      one cDNA library and four PCR-select cDNA subtraction libraries; among these 523
      were clustered into 136 contigs and 675 were singletons. The 811 non-redundant
      uniESTs were compared to GenBank using the Basic Local Alignment Search Tool
      (BLAST) and WU-BLAST algorithms, of these only 489 uniESTs had significant
      sequence homology, which may be involved in resuming the metabolic activity of
      seedlings, switching on photomorphogenesis, fuelling photosynthesis and/or
      initiating the unique developmental programs. Their encoded proteins may
      associate with regulatory proteins to trigger a direct stress response or
      participate in acclimation to environmental stressors. The uniEST platform
      reported will enrich the genomic resources of mungbean for functional genomic
      research on seedling development and chilling response of tropical crops and
      provide targets for improving the chilling tolerance of the tropical crops.

PMID- 18060411
TI  - Walking on smooth or rough ground: passive control of pretarsal attachment in
      ants.
AB  - The hymenopteran tarsus is equipped with claws and a movable adhesive pad
      (arolium). Even though both organs are specialised for substrates of different
      roughness, they are moved by the same muscle, the claw flexor. Here we show that
      despite this seemingly unfavourable design, the use of arolium and claws can be
      adjusted according to surface roughness by mechanical control. Tendon pull
      experiments in ants (Oecophylla smaragdina) revealed that the claw flexor elicits
      rotary movements around several (pre-) tarsal joints. However, maximum angular
      change of claws, arolium and fifth tarsomere occurred at different pulling
      amplitudes, with arolium extension always being the last movement. This effect
      indicates that arolium use is regulated non-neuronally. Arolium unfolding can be
      suppressed on rough surfaces, when claw tips interlock and inhibit further
      contraction of the claw flexor or prevent legs from sliding towards the body. To
      test whether this hypothesised passive control operates in walking ants, we
      manipulated ants by clipping claw tips. Consistent with the proposed control
      mechanism, claw pruning resulted in stronger arolium extension on rough but not
      on smooth substrates. The control of attachment by the insect claw flexor system
      demonstrates how mechanical systems in the body periphery can simplify
      centralised, neuro-muscular feedback control.

PMID- 18060412
TI  - Hirschsprung's disease: 13 years' experience in 112 patients from a single
      institution.
AB  - Although Hirschsprung's disease is curable, a low mortality and a certain
      morbidity have been described by several authors. We will present our experience
      with the treatment of Hirschsprung's disease at Gaslini Children's Hospital. All
      patients who underwent a pull-through procedure since January 1993 were included.
      Data were obtained from a comprehensive questionnaire and from the revision of
      the notes. The results were subsequently described and compared with regard to
      age and length of aganglionosis. A total of 151 patients underwent a pull
      through. One hundred and twelve of these patients completed the forms and were
      reviewed. Eighty patients had a classic form, 22 an ultralong. Complications
      occurred in 28 patients (25%). Postoperative enterocolitis was complained by 25
      patients (13% colonic and 59% ultralong forms) and constipation by 15 (equally
      distributed). Excellent to good continence was experienced by 84% of patients
      with classic forms and by 68% of patients with ultralong forms. A clear improving
      trend during growth was evident for patients with ultralong forms. Psychological
      self-acceptance, patients' perspective and cosmetic results proved to be
      significantly better for patients with classic forms of the disease. Our study
      confirmed the complications and long-term sequelae that patients with
      Hirschsprung's can experience. Early diagnosis can minimise morbidity and
      mortality and prompt and adequate treatment can reduce the incidence of
      postoperative complications. The parents should be acknowledged regarding the
      progressive improvements of function that patients gain during growth,
      particularly in case of ultralong forms, thus strengthening the need for
      continuative care and close follow-up.

PMID- 18060413
TI  - Enteric duplication cysts of the pancreas: a report of two cases and review of
      the literature.
AB  - Enteric duplication cysts are rare congenital malformations that are most
      commonly diagnosed in children. Enteric duplications associated with the pancreas
      are especially uncommon, and may present with specific clinical findings such as
      severe pancreatitis. These cysts often pose unique surgical challenges. In
      addition, the diagnosis of pancreatic duplication cysts is often difficult, and
      may be confused with pancreatic pseudocysts or neoplasms. Herein we report two
      cases of pancreatic duplication cysts, and present a complete tabulation of all
      case reports of pancreatic-associated duplication cysts reported in the English
      literature. We conclude that pancreatic duplication cysts are a rare entity, most
      commonly found to occur in infants and children. We further find that although
      severe complications may arise as a result of their presentation and treatment,
      the rate of post-operative complications in patients between 3 and 21 years of
      age is extremely low, with the highest complication rate occurring in a bimodal
      distribution (<3-years and >21-years of age). Despite complications in the
      youngest and older patient populations, surgical excision remains the mainstay of
      therapy for pancreatic duplication cysts in all age groups.

PMID- 18060414
TI  - The prognostic importance of serum IL-1beta, IL-6, IL-8 and TNF-alpha levels
      compared to trauma scoring systems for early mortality in children with blunt
      trauma.
AB  - The purpose of the present study was to determine whether a correlation exits
      between the main trauma scoring systems and the activation of inflammatory cells
      and mediators such as interleukin-(IL-) 1beta, IL-6, IL-8 and tumor necrosis
      factor alpha (TNF-alpha) after trauma, and moreover to assess if any of these can
      be used to predict the outcome in patients under care at a trauma center. Forty
      seven children (37 boys, 10 girls) presenting with blunt trauma, were evaluated
      by an analysis of the relationship between overall mortality and potential risk
      factors. Admission data, including serum IL-1beta, IL-6, IL-8, TNF-alpha,
      pediatric trauma score (PTS), and injury severity score (ISS), were collected and
      analyzed. In descriptive statistics for independent variables, some prognostic
      factors such as IL-8 (P = 0.04), and ISS (P = 0.004) were significant in their
      relationship to mortality. In the univariate statistical analysis some other risk
      factors such as IL-8 (P = 0.004), >20 TNF-alpha (P = 0.04), and ISS (P = 0.007)
      were significant in their relationship to mortality. The relative risk of
      developing mortality was higher than two for each of the following risk factors:
      >10 ages, >25 IL-6, 10-20 TNF-alpha, >20 TNF-alpha, PTS <or= 8, and ISS > 15.
      There was a positive correlation between IL-8 (r = 0.31, P = 0.33), ISS (r =
      0.31, P = 0.0001), and mortality. There was also a correlation with ISS and IL-8
      (r = 0.32, P = 0.02). ISS, and the serum IL-8 level are the most important
      determinants of clinical outcome in critically injured patients. A correlation
      exits between IL-8 and mortality and between ISS and IL-8.

PMID- 18060415
TI  - Ischemia-reperfusion injury of rabbit ovary and protective effect of trapidil: an
      experimental study.
AB  - We aimed to detect the protective effect of trapidil in ischemia-reperfusion (IR)
      injury due to ovarian torsion and detorsion. Thirty-two pubertal New Zealand
      albino rabbits were used. Adnexal torsion was created by rotating the left adnexa
      including the tubal and ovarian vessels in a 360 degrees clockwise direction.
      Adnexal detorsion was done by untwisting the adnexa. In the IR group, left
      oopherectomy was performed after 3 h of adnexal torsion and 3 h of adnexal
      detorsion. In the study group, a 3-h adnexal torsion was performed and trapidil
      was administered intraperitoneally as a single dose of 40 mg/kg, 1 h before
      detorsion. The left oopherectomy was performed after a 3-h adnexal detorsion. In
      the sham group, sham operation was performed followed by left oopherectomy. In
      the control group, normal ovarian tissue was evaluated. Catalase, superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA)
      levels of ovarian tissue were determined for each group. The values of SOD and
      GSH-Px activities in the IR group were significantly decreased (P < 0.05). In
      addition, the MDA level was significantly higher in the IR group (P < 0.01). The
      trapidil-administered group showed significant increase in the levels of GSH-Px
      (P < 0.05), catalase (P < 0.05), SOD (P < 0.05), and decreased MDA levels (P <
      0.05) compared to those in the IR group. The study has shown that trapidil
      treatment prevents ischemia induced oxidative damage in the ovarian tissues of
      rabbits.

PMID- 18060416
TI  - Comment on Kubota et al.: focal intestinal perforation in extremely-low-birth
      weight neonates: etiological consideration from histological findings.

PMID- 18060417
TI  - The 20th International Symposium on Paediatric Surgical Research.

PMID- 18060418
TI  - Salvage plasmapheresis for small-for-size syndrome following hepatic resection
      for colorectal liver metastases.

PMID- 18060419
TI  - Treatment of osteonecrosis of the hip: comparison of extracorporeal shockwave
      with shockwave and alendronate.
AB  - BACKGROUND AND PURPOSE: Extracorporeal shockwave therapy (ESWT) and alendronate
      are reported effective in early osteonecrosis of the femoral head (ONFH). We
      hypothesized that joint effects of ESWT and alendronate may produce superior
      results. This prospective study compared the results of ESWT and alendronate with
      that of ESWT without alendronate in early ONFH. PATIENTS AND METHODS: Forty-eight
      patients with 60 hips were randomly divided into tow groups. There were 25
      patients with 30 hips in group A and 23 patients with 30 hips in group B. Both
      groups showed similar demographic characteristics. All patients were treated with
      6,000 impulses of ESWT at 28 KV (equivalent to 0.62 mJ/mm(2)) to the affected hip
      as a single session. Patients in group B also received alendronate 70 mg per week
      for 1 year, whereas patients in group A did not. The evaluations included
      clinical assessment, radiograph and MR image of the affected hip. Both groups
      were compared statistically using paired t, Mann-Whitney and Chi square tests
      with statistical significance at P < 0.05. The primary end point is the need for
      total hip arthroplasty (THA). The secondary end point is the improvement in pain
      and function of the hip. The third end point is the progression or regression of
      the lesion on image study. RESULTS: The overall clinical outcomes were improved
      in 83%, unchanged in 7% and worsened in 10% for group A; and improved in 77%,
      unchanged in 13% and worsened in 10% for group B. THA was performed in 10% of
      group A and 10% of group B (P = 1.000). Significant improvements in pain and
      function of the hip were noted in both groups (P < 0.001), however, the
      differences between the two groups were not significant (P = 0.400, 0.313). On MR
      images, the lesions showed progression in 10%, regression in 47% and unchanged in
      43% in group A, and progression in 7%, regression in 53% and unchanged in 40% in
      group B (P = 0.830). CONCLUSION: ESWT and alendronate produced comparable result
      as compared with ESWT without alendronate in early ONFH. It appears that ESWT is
      effective with or without the concurrent use of alendronate. The joint effects of
      alendronate over ESWT in early ONFH are not realized in short-term.

PMID- 18060420
TI  - Fermentable metabolite of Zymomonas mobilis controls collagen reduction in
      photoaging skin by improving TGF-beta/Smad signaling suppression.
AB  - Solar ultraviolet (UV) irradiation causes damages on human skin and premature
      skin aging (photoaging). UV-induced reduction of type I collagen in dermis is
      widely considered primarily induction of wrinkled appearance of photoaging skin.
      Type I procollagen synthesis is reduced under UV irradiation by blocking
      transforming growth factor-beta (TGF-beta)/Smad signaling; more specifically, it
      is down-regulation of TGF-beta type II receptor (T beta RII). Therefore,
      preventing UV-induced loss of T beta RII results decreased type I collagen
      reduction in photoaging skin. Zymomonas mobilis is an alcohol fermentable, gram
      negative facultative anaerobic bacterium whose effect on skin tissue is scarcely
      studied. We investigated the protective effects of fermentable metabolite of Z.
      mobilis (FM of Z. mobilis) against reduction of type I procollagen synthesis of
      UV-induced down-regulation of T beta RII in human dermal fibroblasts FM of Z.
      mobilis was obtained from lyophilization of bacterium culture supernatant. The
      levels of T beta RII and type I procollagen mRNA in human dermal fibroblasts were
      measured by quantitative real-time RT-PCR, and T beta RII protein levels were
      assayed by western blotting. T beta RII, type I procollagen, and type I collagen
      proteins in human dermal fibroblasts or hairless mouse skin were detected by
      immunostaining. FM of Z. mobilis inhibited down regulation of T beta RII mRNA,
      and protein levels in UVB irradiated human dermal fibroblasts consequently
      recover reduced type I procollagen synthesis. These results indicate UVB
      irradiation inhibits type I procollagen synthesis by suppression of TGF-beta/Smad
      signaling pathway, and FM of Z. mobilis has inhibitory effect on UVB-induced
      reduction of type I procollagen synthesis. While short period UVB irradiation
      decreased both T beta RII and type I procollagen protein levels in hairless mouse
      skin, topical application of FM of Z. mobilis prevented this decrease. Wrinkle
      formation in hairless mouse skin surface was accelerated by continuous 5 month
      UVB irradiation along with a reduction of type I collagen in the dermis, but this
      change was prevented by topical application of FM of Z. mobilis. From this
      experimental data, it is suggested that FM of Z. mobilis is effective for
      suppression of wrinkle formation in photoaging skin by inhibition of type I
      procollagen synthesis reduction.

PMID- 18060421
TI  - Combined effects of radiotherapy and endostatin gene therapy in melanoma tumor
      model.
AB  - PEgr-Endostatin-EGFP plasmid was constructed to investigate its expression
      properties induced by ionizing irradiation and the effect of pEgr-Endostatin-EGFP
      gene-radiotherapy on melanoma tumor-bearing mice. The pEgr-Endostatin-EGFP
      plasmid was transfected into B16 cell line with liposome. The expression property
      of endostatin was investigated by RT-PCR and that of EGFP was detected by flow
      cytometry. Tumor-bearing mice were treated by the plasmid injection and 2 Gy X
      irradiation of three fractions. Tumor growth was observed for 18 days after
      treatment. Change of tumor capillary formation was measured with histochemistry
      assay at the end of the experiment. The expression of GFP in B16 melanoma cells
      was detected after X-irradiation with 0.05-20 Gy. Time-course studies showed that
      the expression of GFP in B16 cells reached its peak at 8 h after irradiation with
      2 Gy. The injection of pEgr-Endostatin-EGFP recombinant plasmid into the
      implanted B16 melanoma in C57BL/6J mice followed by local X-irradiation could
      significantly inhibit tumor growth with inhibition of intratumor micro-vessel
      density. The inhibitory effect of pEgr-Endostatin-EGFP gene-radiotherapy on the
      growth of B16 melanoma is correlated with the marked decrease of intratumoral
      vascularization. The present data point to the potential of an anti-angiogenic
      approach in gene-radiotherapy of cancer.

PMID- 18060422
TI  - Beyond the code: the mechanical properties of DNA as they relate to mitosis.

PMID- 18060423
TI  - Assessment of the effects of environmental radiation on wind chill equivalent
      temperatures.
AB  - Combinations of wind-driven convection and environmental radiation in cold
      weather, make the environment "feel" colder. The relative contributions of these
      mechanisms, which form the basis for estimating wind chill equivalent
      temperatures (WCETs), are studied over a wide range of environmental conditions.
      Distinction is made between direct solar radiation and environmental radiation.
      Solar radiation, which is not included in the analysis, has beneficial effects,
      as it counters and offsets some of the effects due to wind and low air
      temperatures. Environmental radiation effects, which are included, have
      detrimental effects in enhancing heat loss from the human body, thus affecting
      the overall thermal sensation due to the environment. The analysis is performed
      by a simple, steady-state analytical model of human-environment thermal
      interaction using upper and lower bounds of environmental radiation heat
      exchange. It is shown that, over a wide range of relevant air temperatures and
      reported wind speeds, convection heat losses dominate over environmental
      radiation. At low wind speeds radiation contributes up to about 23% of the
      overall heat loss from exposed skin areas. Its relative contributions reduce
      considerably as the time of the exposure prolongs and exposed skin temperatures
      drop. At still higher wind speeds, environmental radiation effects become much
      smaller contributing about 5% of the total heat loss. These values fall well
      within the uncertainties associated with the parameter values assumed in the
      computation of WCETs. It is also shown that environmental radiation effects may
      be accommodated by adjusting reported wind speeds slightly above their reported
      values.

PMID- 18060424
TI  - Survival benefits of pancreatoduodenectomy for gastric cancer: relationship to
      the number of lymph node metastases.
AB  - BACKGROUND AND AIMS: Pancreatoduodenectomy (PD) for advanced gastric cancer is
      rarely performed because of the high frequency of associated morbidity and
      mortality. The aim of this study was to determine the limited indication of PD
      for advanced gastric cancer. MATERIALS AND METHODS: From January 1984 and
      December 2005 patient's charts were reviewed and outcomes after PD for gastric
      cancer were compared between two subgroups; those with a 'high' number (7<or=
      group) of lymph node metastases and those with 'low' numbers (6>or= group).
      RESULTS: PD was intraoperatively selected because of direct tumor invasion into
      the pancreas (52.2% of the 7<or= group vs 12.5% of the 6>or= group) or pancreatic
      lymph node infiltration (47.8% of the 7<or= group vs 87.5% of the 6>or= group; P
      = 0.058). The postoperative histological analysis showed 22 cases from 23 (95.7%)
      in 7<or= group with T3 or T4 tumor, compared with only 4 cases (50%) in 6>or=
      group (P = 0.014). The 5-year survival rates were significantly better in the
      6>or= group compared with the 7<or= group (P = 0.014). CONCLUSIONS: The
      indication for PD in advanced gastric cancer should consider the degree of
      extensive lymph node metastases and incurable factors.

PMID- 18060425
TI  - Coelomic expression of a novel bone morphogenetic protein in regenerating arms of
      the brittle star Amphiura filiformis.
AB  - The bone morphogenetic proteins (BMPs) are a family of signalling molecules
      involved in numerous developmental processes including cell fate determination in
      embryonic ectoderm of vertebrate and invertebrate species. Recently, published
      evidence has indicated that BMPs are involved in echinoderm adult tissue
      regeneration. We have cloned a novel member of the BMP2/4 subfamily from the
      ophiuroid echinoderm Amphiura filiformis, which we have named afBMP2/4. Whole
      mount in-situ hybridisation performed on non-regenerating brittle star arms
      revealed that expression of afBMP2/4 is localised to the radial water canal (RWC)
      and that this expression is upregulated at segmental intervals along the arm.
      This observed expression pattern suggests a putative active role for this
      echinoderm BMP transcript in somatic growth and maintenance of the brittle star
      arm. Expression of this factor has also been observed in regenerating arms 2
      weeks post-ablation, implicating the RWC as a source of cells for ophiuroid arm
      regeneration.

PMID- 18060426
TI  - Total tibia replacement using an allograft (in a patient with adamantinoma). Case
      report and review of literature.
AB  - INTRODUCTION: Adamantinoma is a very rare, low-grade, malignant bone tumour that
      accounts for approximately 0.4% of all primary bone tumours. Radiographically,
      adamantinomas vary in length, have a clearly defined outline, with a bubbly
      appearance and increase the width of the bone. Histologically, epithelial cells,
      endothelial cells synovial cells have been implicated as cells of origin. CASE
      PRESENTATION: We present a case of adamantinoma of the tibia, in which a
      resection of the whole tibia and reconstruction with a total tibia allograft was
      necessary. DISCUSSION: The histological diagnosis is sophisticated. It is often
      difficult to distinguish an adamantinoma from other tumours. The most frequent
      described method to treat adamantinoma is wide resection and the use of an
      allograft. The most common complication is fracture presented similarly in our
      patient. CONCLUSION: A total tibia allograft as presented in our case is not
      described in the literature. It fractured due the first year after implantation.
      Using a prosthesis system instead of the allograft might have saved the limb of
      our patient.

PMID- 18060427
TI  - New host record, Parablennius sanguinolentus (Teleostei, Perciformes, Blenniidae)
      for Nerocila bivittata (Crustacea, Isopoda, Cymothoidae).
AB  - Nerocila bivittata (Crustacea, Isopoda, Cymothoidae) is reported for the first
      time on the caudal peduncle of the Rusty blenny, Parablennius sanguinolentus
      (Teleostei, Perciformes, Blenniidae), collected from Samsun Coast, Black Sea,
      Turkey. N. bivittata parasitized 7.4% (2 of 27) of the P. sanguinolentus
      collected.

PMID- 18060428
TI  - Plasmodium malariae infection in spite of previous anti-malarial medication.
AB  - Plasmodium malariae is regarded as usually being susceptible to all anti
      malarials whether applied for prophylaxis or treatment. We report on three cases
      of P. malariae infection which occurred 12-14 weeks after anti-malarial
      chemoprophylaxis or treatment with mefloquine or atovaquone/proguanil. The most
      likely explanation for the failure of mefloquine and atovaquone/proguanil to
      prevent quartan malaria occurring some months later is the insufficient effect on
      the particularly long-lasting pre-erythrocytic development stages of P. malariae.

PMID- 18060429
TI  - The stomal morphology of parasitic females of Strongyloides spp. by scanning
      electron microscopy.
AB  - For the discrimination of the species of the genus Strongyloides, the shape of
      the stoma in the apical view of parasitic females is the most important feature.
      Microscopical interpretations divided the shape of the stoma into four groups
      (simple, angular, complex, and simple but with esophageal teeth); however, the
      stomas classified in the latter two groups, in particular, remained unclear. In
      the present study, parasitic females of eight representative Strongyloides spp.
      with the angular stoma (S. procyonis and S. martis), complex stoma (S. robustus,
      S. callosciureus, S. planiceps, S. papillosus and S. myopotami), and stoma with
      esophageal teeth (S. ransomi) were studied by scanning electron microscopy. All
      species examined in this study having complex stoma or with esophageal teeth
      possessed at least four linguiform or verruciform projections submarginally in
      the stomal cavity. Namely, the number, size, shape, and the site of attachment of
      intra-stomal projections, along with the depth of oral cavity, determine a range
      of complex images of the stoma such as X-shaped or ornate stomas under light
      microscopy. Similarly, with the standard examination, which usually uses a
      lateral view of the head, erroneous interpretations of the number of lobes on the
      circumoral elevation of parasitic females might occur due to such intra-stomal
      projections in some Strongyloides spp.

PMID- 18060430
TI  - Identification of stage-specific proteins of Angiostrongylus vasorum (Baillet,
      1866) Kamensky.
AB  - Sera of ten dogs infected with Angiostrongylus vasorum were analyzed by
      immunoblotting proteins of first stage larvae (L1) and adult parasites. The
      molecular weights (m.w.) of the principal L1 proteins identified by IgG, IgM,
      IgA, and IgE were 18-118 kDa and those of the adult parasite were 28-209 kDa. The
      L1 proteins had not been recognized by IgG, IgM, and IgA antibodies in sera of
      dogs naturally infected with Toxocara canis, Ancylostoma caninum, and Dipylidium
      caninum, although only weakly by IgE. Adult parasite proteins were recognized by
      antibodies in sera of dogs naturally infected with gastrointestinal helminths.
      Adult parasite proteins with m.w. of approximately 51, 63, 92, and 209 kDa
      recognized by IgG could be used for specific diagnosis of canine
      angiostrongylosis.

PMID- 18060431
TI  - CP2 gene as a useful viability marker for Cryptosporidium parvum.
AB  - The validity of the CP2 gene of Cryptosporidium parvum as a viability marker was
      evaluated using absolute quantitative real-time polymerase chain reaction (qPCR)
      assays. Total ribonucleic acid (RNA) was isolated from live and heat-killed C.
      parvum oocysts, and complementary deoxyribonucleic acid was synthesized and used
      as a template. The most accurate number of viable C. parvum oocysts was predicted
      when the CP2 gene was used as a target gene. The lower detection limit of the CP2
      gene was ten oocysts, which was the most sensitive among examined target genes.
      With heat shock induction, only hsp70 messenger RNA (mRNA) was induced, and the
      predicted viable oocyst number was increased by heat shock for this marker. The
      CP2, hsp70, Cryptosporidium oocyst wall protein, and beta-tubulin mRNAs were not
      detected in heat-killed oocysts, but the 18S ribosomal ribonucleic acid (rRNA)
      showed heat stability until 48 h after heat killing. Although the 18S rRNA
      demonstrated the fastest response in crossing point (CP) value among the examined
      primer sets in qPCR, overestimation of viable oocysts was noted in the analysis
      with this gene. In conclusion, the CP2 gene was identified as the most sensitive,
      reliable, and accurate candidate of a viability marker of C. parvum by qPCR
      evaluation.

PMID- 18060433
TI  - Comments on the entropy-based transmission/disequilibrium test.
AB  - It has recently been claimed in this journal (Zhao et al. in Hum Genet 121:357
      367, 2007) that a so-called "entropy-based" TDT test has improved power over the
      standard TDT test of Spielman et al. (Am J Hum Genet 52:506-516, 1993). We show
      that this claim is contradicted by standard statistical theory as well as by our
      simulation results. We show that the incorrect claim arises because of
      inappropriate assumptions, and also show that the entropy-based statistic has
      various undesirable properties.

PMID- 18060434
TI  - Pollinator-mediated selfing in two deceptive orchids and a review of pollinium
      tracking studies addressing geitonogamy.
AB  - Among the factors thought to have favoured the evolution of deception
      (rewardlessness) in orchids is the reduction of pollinator-mediated selfing when
      unrewarded pollinators visit fewer flowers per inflorescence. We obtained data on
      natural levels of geitonogamy in the deceptive orchids Dactylorhiza sambucina and
      Himantoglossum hircinum by monitoring the dispersal and receipt of colour-coded
      pollinia. As donors, we marked 185 flowers of D. sambucina and 956 flowers of H.
      hircinum. In D. sambucina, 30% of the pollinator-visited flowers and 62% of the
      marked inflorescences experienced geitonogamous pollination events. In H.
      hircinum, the respective percentages were 36 and 71%. The furthest pollen
      transport distance in the Andrena-pollinated H. hircinum was 6.9 m (median 1.27
      m), while the furthest transport in the bumblebee-pollinated D. sambucina was 176
      m (median 1.23 m), a record in Orchidaceae. An analysis of pollen-tracking
      studies in orchids revealed geitonogamy levels of around 40% (based on
      individuals; 19-37% based on flowers) in both rewardless species and rewarding
      ones. This is similar to geitonogamy levels in other animal-pollinated
      angiosperms, although the data basis for comparison may still be too small. So
      far, however, it is not evident that rewardless orchids experience particularly
      low levels of geitonogamy.

PMID- 18060432
TI  - Functional characterization of the putative Aspergillus nidulans DNA damage
      binding protein homologue DdbA.
AB  - Nucleotide excision repair (NER) eliminates helix-distorting DNA base lesions.
      Seven XP-deficient genetic complementation groups (XPA to XPG) have already been
      identified in mammals, and their corresponding genes have been cloned. Hereditary
      defects in NER are associated with several diseases, including xeroderma
      pigmentosum (XP). UV-DDB (XPE) is formed by two associated subunits, DDB1 and
      DDB2. UV-DDB was identified biochemically as a protein factor that exhibits very
      strong and specific binding to ultraviolet (UV)-treated DNA. As a preliminary
      step to characterize the components of the NER in the filamentous fungus
      Aspergillus nidulans, here we identified a putative DDB1 homologue, DdbA.
      Deletion and expression analysis indicated that A. nidulans ddbA gene is involved
      in the DNA damage response, more specifically in the UV light response and 4
      nitroquinoline oxide (4-NQO) sensitivity. Furthermore, the DeltaddbA strain
      cannot self-cross and expression analysis showed that ddbA can be induced by
      oxidative stress and is developmentally regulated in both asexual and sexual
      processes. The DeltaddbA mutation can genetically interact with uvsB (ATR),
      atmA(ATM), nkuA (KU70), H2AX-S129A (a replacement of the conserved serine in the
      C-terminal of H2AX with alanine), and cshB (a mutation in CSB Cockayne's syndrome
      protein involved in the transcription-coupled repair subpathway of NER)
      mutations. Finally, to determine the DdbA cellular localization, we constructed a
      GFP::DdbA strain. In the presence and absence of DNA damage, DdbA was mostly
      detected in the nuclei, indicating that DdbA localizes to nuclei and its cellular
      localization is not affected by the cellular response to DNA damage induced by 4
      NQO and UV light.

PMID- 18060435
TI  - Role of the renin angiotensin system in TNF-alpha and Shiga-toxin-induced tissue
      factor expression.
AB  - Current evidence implicates a prothrombotic state in the development of Shiga
      toxin (Stx)-mediated hemolytic uremic syndrome (HUS). We recently reported that
      Stx modulates procoagulant activity by enhancing functional tissue factor (TF)
      activity on cytokine-activated human glomerular endothelial cells (HGECs). Since
      angiotensin II (Ang II), the key effector of the renin angiotensin system (RAS),
      has been shown to increase TF expression in vascular tissue, we examined the
      possible involvement of Ang II in TF expression in HGECs. HGECs were exposed to
      tumor necrosis factor (TNF)-alpha +/- Stx-1 +/- Ang II. Exogenous Ang II
      significantly increased TF activity and TF mRNA in TNF-alpha- +/- Stx-1-activated
      HGECs. This increase was mediated via Ang II type I receptor (AT(1)R), as
      losartan, an AT(1)R inhibitor, attenuated Ang-II-induced TF activity. To study
      the effect of endogenous Ang II in TF expression by TNF-alpha +/- Stx-1, HGECs
      were incubated with losartan or an AT(2)R inhibitor (PD 123319) or an angiotensin
      converting enzyme inhibitor (enalapril). Losartan but not PD 123319 decreased TF
      activity induced by TNF-alpha +/- Stx-1 (P < 0.05). Enalapril, also, dose
      dependently, downregulated TF expression in HGECs exposed to TNF-alpha +/- Stx-1
      (P < 0.05). AT(1)R mRNA was upregulated in TNF-alpha- +/- Stx-1-activated HGECs
      (P < 0.05). These data indicate that TF expression in TNF-alpha- and Stx-1
      activated HGECs is enhanced by exogenous Ang II and that endogenous Ang II
      production may be upregulated by TNF-alpha +/- Stx-1. Hence, local RAS activation
      may be important in the development of the thrombotic microangiopathy observed in
      HUS.

PMID- 18060436
TI  - Different spectra of genomic deletions within the CCM genes between Italian and
      American CCM patient cohorts.
AB  - Cerebral cavernous malformations (CCMs) are vascular abnormalities of the brain
      that can result in hemorrhagic stroke and seizures. Familial forms of CCM are
      inherited in an autosomal-dominant fashion, and three CCM genes have been
      identified. We recently determined that large genomic deletions in the CCM2 gene
      represent 22% of mutations in a large CCM cohort from the USA. In particular, a
      77.6 kb deletion spanning CCM2 exons 2-10 displays an identical recombination
      event in eight CCM probands/families and appears to be common in the US
      population. In the current study, we report the identification of six additional
      probands/families from the USA with this same large deletion. Haplotype analysis
      strongly suggests that this common deletion derives from an ancestral founder. We
      also examined an Italian CCM cohort consisting of 24 probands/families who tested
      negative for mutations in the CCM1, CCM2, and CCM3 genes by DNA sequence
      analysis. Surprisingly, the common CCM2 deletion spanning exons 2-10 is not
      present in this population. Further analysis of the Italian cohort by multiplex
      ligation-dependent probe analysis identified a total of ten deletions and one
      duplication. The overall spectrum of genomic rearrangements in the Italian cohort
      is thus quite different than that seen in a US cohort. These results suggest that
      there are elements within all three of the CCM genes that predispose them to
      large deletion/duplication events but that the common deletion spanning CCM2
      exons 2-10 appears to be specific to the US population due to a founder effect.

PMID- 18060437
TI  - Prospective object search in dogs: mixed evidence for knowledge of What and
      Where.
AB  - We investigated whether two dogs that had been specially trained to retrieve
      objects by their names were able to integrate information about the identity
      (What) as well as the location (Where) of those objects so that they could plan
      their search accordingly. In a first study, two sets of objects were placed in
      two separate rooms and subjects were asked to retrieve the objects, one after the
      other. Both dogs remembered the identity of the objects as they reliably
      retrieved the correct objects. One of the dogs was also able to integrate
      information about the object's location as he chose the correct location in which
      the object had been placed. Further investigation of the second dog's behavior
      revealed that she followed a more stereotyped search strategy. Despite this
      variation in performance, this study provides evidence for the memory of What and
      Where in a domestic dog and shows the prospective use of such information in a
      search task.

PMID- 18060438
TI  - Clinician response to Candida organisms in the urine of patients attending
      hospital.
AB  - The epidemiology of 54 episodes of candiduria with respect to clinical risk
      factors, species of Candida and physician response to the isolation of Candida in
      urine were studied in an observational survey over 3 months. Candida spp. were
      isolated from 4.7% of positive urine cultures. Common predisposing conditions
      included antibiotic use (74.1%), urinary drainage devices (57.4%), surgery
      (51.9%), intensive care unit (ICU) or high-dependency care unit (HDU) admission
      (42.6%) and urinary tract (UT) disease (18.5%). Upper UT infection was uncommon
      (n = 3). Of 65 Candida isolates, C. albicans predominated (85.2%), followed by C.
      glabrata (27.8%) and other Candida spp. (6.2%). All isolates were susceptible to
      fluconazole, itraconazole, voriconazole, amphotericin and caspofungin. Indwelling
      urinary catheters were removed in 76.2% of episodes. Antifungal therapy was
      initiated in 33.3% of cases independently of patient symptoms, underlying disease
      or Candida colony count. Patients in ICU/HDUs were significantly more likely to
      receive antifungal agents than those outside these units (p < 0.001). Fluconazole
      was the most common drug prescribed (77.8%). Clearance of candiduria occurred
      independently of antifungal therapy (p = 0.60). Physicians often did not follow
      up a positive urine result for Candida. Efforts to increase clinician awareness
      of current recommendations for managing candiduria and further study to elucidate
      specific risk factors in defined patient populations are warranted.

PMID- 18060439
TI  - Pneumococcal meningitis in the era of pneumococcal conjugate vaccine
      implementation.
AB  - The French Pediatric Infectious Diseases Group set up an active surveillance
      network to analyze the clinical and biological features of pneumococcal
      meningitis and the impact of the seven-valent pneumococcal conjugate vaccine
      (PCV7). From 2001 to 2005, 234 pediatric wards working with 166 microbiology
      laboratories enrolled all children with pneumococcal meningitis. Risk factors,
      signs and symptoms, vaccination status, cerebrospinal fluid analysis, treatments
      and case fatality rates were recorded. One hundred and sixty-nine centers
      (169/234) reported 616 cases, median age was 0.9 years and 67.2% of children were
      < or =2 years old. Underlying conditions were present in 13.1% of cases. The
      proportion of penicillin non-susceptible strains was 48.7%. Vancomycin plus a
      third-generation cephalosporin was prescribed in 92.7% of cases, and steroids
      were given before antibiotic treatment in 16.5% of cases. The case fatality rate
      was 10.8% overall and was not related to age, antibiotic susceptibility or
      steroid use. In children 2 to 24 months old compared to the prevaccinal period
      (2001-2002) a decrease of 28.4% of the number of cases was observed in 2005 (P <
      0.05). Among children 2 to 24 months old, the proportion of serotypes covered by
      the PCV7 fell from 39/57 (68.4%) in 2001-2002 to 19/45 (42.2%) in 2005, while the
      proportion of non-vaccine serotypes and related serotypes increased respectively
      from 9/57 (15.8%) and 9/57 (15.8%) in 2001-2002 to 14/45 (31.1%) and 12/45
      (26.7%) in 2005. Among 52 cases of pneumococcal meningitis that have occurred in
      vaccinated children (> or =1 dose) with PCV7, 7 were due by vaccine serotypes.
      This study provides data on underlying conditions, penicillin susceptibility,
      serotype evolution according to vaccination status and risk factors for mortality
      for pneumococcal meningitis in children from 2001-2005 in France.

PMID- 18060441
TI  - Effect of ramelteon, a selective MT(1)/MT (2)-receptor agonist, on respiration
      during sleep in mild to moderate COPD.
AB  - Ramelteon, a selective MT(1)/MT(2) melatonin receptor agonist, was evaluated in
      subjects with mild to moderate chronic obstructive pulmonary disease (COPD) to
      determine whether it would have a negative effect on measures of safety and
      respiration. This randomized, double-blind, crossover study in 26 subjects with
      mild to moderate COPD compared the effects of a single bedtime dose of ramelteon
      16 mg and placebo on sleep, oxygenation, and sleep-related abnormal breathing
      events. Compared with placebo, ramelteon had no statistically significant effect
      on mean arterial oxygen percent saturation (SaO(2)) for the entire night (92.9 vs
      92.9%; 95% confidence interval [CI], -0.6 to 0.6; P = 0.972), for each of the 8 h
      of the night, for each sleep stage (awake, rapid eye movement, nonrapid eye
      movement) or for the percentage of the night that SaO(2) was less than 85 and
      90%. The mean apnea-hypopnea index was similar between ramelteon and placebo
      groups (9.0 vs 8.3; 95% CI, -1.5 to 3.0; P = 0.515). Polysomnography documented a
      significant increase in total sleep time (380.6 vs 353.6, P = 0.015), sleep
      efficiency (79.3 vs 73.7, P = 0.017), and number of awakenings (11.1 vs 9.5, P =
      0.036) with ramelteon vs placebo. Other polysomnography and subject-reported
      sleep measures were comparable between groups. Only one adverse event was
      reported; it was not considered treatment related. No clinically meaningful
      changes in laboratory test results, vital signs, electrocardiogram, and physical
      examination were observed. In this study, ramelteon 16 mg (two times the
      recommended therapeutic dose) showed no clinically meaningful or statistically
      significant effects on oxygenation or abnormal breathing events, was well
      tolerated, and improved sleep duration and efficiency in subjects with mild to
      moderate COPD.

PMID- 18060442
TI  - [Minimally invasive implantation in unicondylar arthroplasty].
AB  - Knee arthroplasty has become one of the most successful standard procedures in
      orthopaedic surgery. With a more frequent use in young and active patients bone
      saving procedures have become more important. The goal is to save good bone stock
      for the revision procedure. Therefore, unicompartmental knee arthroplasty is a
      good example. Instrumentation and minimally invasive surgical techniques have
      been improved so very good long-term results and early functional results are
      achieved. The paper describes the surgical technique with true capsule incision
      and extramedullary alignment technique. In a prospective study, the early
      functional results with the ZUK implant were excellent. The implant may not be
      indicated for every knee situation and an exact differential indication and sound
      surgical technique are necessary. Its use, however, in cases with
      unicompartmental knee arthritis, contributes to excellent early rehabilitation
      and to maintaining autologous bone. Therefore, the minimally invasive
      unicompartmental knee arthroplasty is a sensible alternative to other options.

PMID- 18060443
TI  - [Indications and techniques for wrist arthroscopy].
AB  - After considering the anatomy of the wrist, the technical requirements for wrist
      arthroscopy are discussed. This method is used as an additional diagnostic
      procedure and staging procedure as well as a therapeutic technique.
      Complications, which are rare, most commonly involve nerve irritation, damage to
      cutaneous nerves and extensor tendons. Lose bodies can be removed
      arthroscopically, however, arthroscopically assisted fracture treatment or the
      removal of ganglions are uncommon. Approaches are lateral and oriented on the
      extensor tendons or other anatomical landmarks. Arthroscopy is especially useful
      by carpal instability as it offers many possibilities, not only diagnostically
      but also therapeutically.

PMID- 18060440
TI  - Serpins in plants and green algae.
AB  - Control of proteolysis is important for plant growth, development, responses to
      stress, and defence against insects and pathogens. Members of the serpin protein
      family are likely to play a critical role in this control through irreversible
      inhibition of endogenous and exogenous target proteinases. Serpins have been
      found in diverse species of the plant kingdom and represent a distinct clade
      among serpins in multicellular organisms. Serpins are also found in green algae,
      but the evolutionary relationship between these serpins and those of plants
      remains unknown. Plant serpins are potent inhibitors of mammalian serine
      proteinases of the chymotrypsin family in vitro but, intriguingly, plants and
      green algae lack endogenous members of this proteinase family, the most common
      targets for animal serpins. An Arabidopsis serpin with a conserved reactive
      centre is now known to be capable of inhibiting an endogenous cysteine
      proteinase. Here, knowledge of plant serpins in terms of sequence diversity,
      inhibitory specificity, gene expression and function is reviewed. This was
      advanced through a phylogenetic analysis of amino acid sequences of expressed
      plant serpins, delineation of plant serpin gene structures and prediction of
      inhibitory specificities based on identification of reactive centres. The review
      is intended to encourage elucidation of plant serpin functions.

PMID- 18060444
TI  - Autofluorescence bronchoscopy: quantification of inter-patient variations of
      fluorescence intensity.
AB  - Autofluorescence (AF) from bronchial tissue is increasingly used for the
      endoscopic detection of early bronchial neoplasia. Several imaging systems are
      commercially available, all detecting the absolute or relative AF intensity
      and/or spectral contrasts between normal tissue and early neoplastic lesions.
      These devices have a high sensitivity for flat neoplasia, but the specificity
      remains limited. Variations in the AF intensity between individuals (inter
      patient variations) is considered one of the most limiting factors. In the
      clinical study presented here, we quantified those variations using a non
      invasive optical reference positioned in situ during AF bronchoscopy. The inter
      patient variations in intensity on the main carina were in the order of 25- 30%.
      The results of this study are quite useful for improving and defining the design
      of the optical features (dynamic range, physical sensitivity) of AF detection
      systems.

PMID- 18060445
TI  - Congenital right atrial aneurysm in an infant.
AB  - A 4-month-old infant with right atrial aneurysm, presenting with recurrent
      episodes of lower respiratory tract infection is described. There was no history
      of supraventricular tachyarrhythmias or embolic events. Transthorasic
      echocardiography definitely showed an aneurysmal sac (3.7 A-4.2 cm) originating
      from the right atrium with compressing effect on left side cardiac structures.
      Surgical excision of aneurysm allowed removal of mass effect and clinical
      improvement.

PMID- 18060446
TI  - Midaortic syndrome presenting as neonatal hypertension.
AB  - We describe a case of mid-aortic syndrome presenting as systemic hypertension in
      infancy and early childhood. Angiography of the descending and abdominal aorta is
      the diagnostic test of choice to confirm the diagnosis of mid-aortic syndrome.
      Severity of hypertension is one of the major factors in determining the timing of
      intervention. Because of variability in the anatomic extent of mid-aortic
      syndrome, management options need to be individualized.

PMID- 18060447
TI  - Acute coronary syndrome as a first presentation of systemic lupus erythematosus
      in a teenager: revascularization by hybrid coronary artery bypass graft surgery
      and percutaneous coronary intervention: case report.
AB  - Patients with systemic lupus erythematosus (SLE) may present with acute coronary
      syndrome (ACS) due to coronary vasculitis or premature atherosclerosis. There is
      a paucity of data on invasive management strategies for young adults who present
      with an ACS secondary to active vasculitis. This article describes the case of a
      teenager who presented with an ACS secondary to lupus vasculitis as his first
      presentation of active SLE. Coronary angiography showed a left main equivalent
      lesion involving a proximal very large left anterior descending artery (LAD) and
      diagonal stenosis (with a diminutive left circumflex artery). The boy underwent a
      successful endoscopic coronary bypass surgery to his LAD followed by percutaneous
      coronary intervention to his diagonal artery. This case demonstrates the
      feasibility and safety of a hybrid coronary revascularization in a teenager with
      acute coronary syndrome due to coronary vasculitis.

PMID- 18060448
TI  - Diversity of rhizobial bacteria isolated from nodules of the Gypsophyte Ononis
      tridentata L. growing in Spanish soils.
AB  - The aim of this work is to describe the diversity and phylogeny of rhizobial
      bacteria associated to nodules of Ononis tridentata L. in different geographical
      regions of Spain. Twenty-two bacterial isolates were characterized using several
      molecular techniques (16S amplified ribosomal deoxyribonucleic acid restriction
      analysis, fingerprinting, and sequencing) and phylogenies were inferred from
      their 16S and nodC gene sequences. Phylogenetically, the isolates grouped with
      the genera Rhizobium, Mesorhizobium, Phylobacterium, and Bosea. The nodC gene,
      essential for nodulation, was detected for the first time in isolates close to
      the genera Bosea and Phyllobacterium. The bacteria isolated showed a high
      diversity at the genus, species, and strain level regardless of the geographical
      origin of the host plant. This is the first report describing bacteria associated
      to nodules of O. tridentata. This shrub legume is highly prized for the
      revegetation of gypsum soils in semiarid Mediterranean areas. Our molecular
      description of bacteria associated to this legume improves the current
      understanding of the ecology of this plant species. Our findings have
      implications for formulating suitable bacterial inocula to recover gypsum
      ecosystems.

PMID- 18060450
TI  - Isolated spring wetlands in the Great Basin and Mojave deserts, USA: potential
      response of vegetation to groundwater withdrawal.
AB  - Desert springs, often the sole sources of water for wildlife and cattle, support
      wetland and wetland/upland transition ecosystems including rare and endemic
      species. In the basin and range province in Nevada, USA, springs in the Great
      Basin and Mojave deserts are sustained by interconnected deep carbonate and
      shallow basin-fill aquifers which are threatened by proposed groundwater
      withdrawal to sustain rapidly expanding urban areas, a common problem in arid
      regions worldwide. This paper draws on historic groundwater data, groundwater
      modeling, and studies of environmental controls of spring ecosystems to speculate
      on the potential effects of groundwater withdrawal and water table decline on
      spring-supported vegetation. The focus is on springs in the Great Basin and
      Mojave deserts representative of those that may be affected by future, planned
      groundwater withdrawal. Groundwater withdrawal is expected to reduce spring
      discharge directly through reduced flows from the shallow basin-fill aquifer or
      through reduction of the hydraulic head of the deep carbonate aquifer. This flow
      reduction will truncate the outflow stream, reducing the areal cover of wetland
      and wetland/upland transition vegetation. Lowering the local water table may also
      reduce the amount of upland phreatophytic vegetation by causing water levels to
      drop below plant rooting depths. Percolation of salts to surface soils may be
      reduced, eventually altering desert shrub cover from halophytes to nonhalophytes.
      The extent of these effects will vary among springs, based on their distance from
      extraction sites and location relative to regional groundwater flow paths. On
      site monitoring of biotic variables (including cover of selected hygrophytes and
      phreatophytes) should be a necessary complement to the planned monitoring of
      local hydrologic conditions.

PMID- 18060449
TI  - Sugar beet-associated bacterial and fungal communities show a high indigenous
      antagonistic potential against plant pathogens.
AB  - The aim of this study was to analyze microbial communities in/on sugar beet with
      special focus on antagonists toward plant pathogens. For this purpose, the
      composition of microorganisms isolated from the rhizosphere, phyllosphere,
      endorhiza, and endosphere of field-grown sugar beet plants was analyzed by a
      multiphasic approach at three different plant development stages at six locations
      in Europe. The analysis of microbial communities by Single Strand Conformation
      Polymorphism (SSCP) of 16S/18S rRNA clearly revealed the existence of discrete
      microenvironment- and site-specific patterns. A total of 1952 bacterial and 1344
      fungal isolates screened by dual testing for antagonism toward the pathogens
      Aphanomyces cochlioides, Phoma betae, Pythium ultimum, and Rhizoctonia solani
      resulted in 885 bacterial (=45%) and 437 fungal (=33%) antagonists. In general,
      the indigenous antagonistic potential was very high and influenced by (a) the
      location, (b) the plant developmental stage, and (3) the microenvironment.
      Furthermore, we showed for the first time that the antagonistic potential was
      highly specific for each target pathogen. The majority of antagonistic
      microorganisms suppressed only one pathogen (bacteria: 664 = 75%; fungi: 256 =
      59%), whereas the minority showed a broad host range (bacteria: 4 = 0.5%; fungi:
      7 = 1.6%). The bacterial communities harbored the highest antagonistic potential
      against P. ultimum, whereas the fungal communities contained more antagonists
      against A. cochlioides and R. solani. In contrast to their high proportion, only
      a low diversity of antagonists at genotypic and species level was found. Novel
      antagonistic species, e.g., Subtercola pratensis or Microbacterium testaceum were
      found in the internal part of the sugar beet body.

PMID- 18060451
TI  - Surgery for body packing in the Caribbean: a retrospective study of 70 patients.
AB  - BACKGROUND: Body packing is a way to deliver packages of drugs hidden in body
      cavities, across international borders. This may cause mechanical bowel
      obstruction and intoxication leading to emergency surgery. The objective of this
      retrospective study is to evaluate pre-, per- and postoperative characteristics
      of body packing and its complications and prognosis after surgery. METHODS:
      Medical information was obtained from 70 patients diagnosed with Body Packer
      syndrome who underwent surgery for body packing in the period of July 2001-July
      2005 at the St. Elisabeth hospital, Curacao, the Netherlands Antilles. RESULTS:
      Wound infection occurred in 32.9% and fascia dehiscence in 2.9%. Most procedures
      were enterotomies. One patient had a re-laparotomy for Hartmann's procedure
      because of an anastomotic leak and three other patients had a partial small bowel
      resection. The creation of a stoma was only needed in one patient. One patient
      died of postoperative DIC. In six patients packages were left behind, not
      requiring re-operation. CONCLUSIONS: Bowel obstruction and symptoms of
      intoxication are clear indications for surgery in body packing patients. In our
      study there was a low mortality and stoma placement rate, we did find a
      remarkable high amount of wound infection but no evidence for a higher incidence
      of fascia dehiscence in comparison with elective gastrointestinal surgery. In
      surgery for bodypacking a mandatory postoperative x-ray is indicated. A
      prospective trial is needed to assess more information about possible predictive
      factors of postoperative complications and mortality after surgery for body
      packing.

PMID- 18060452
TI  - Post-mastectomy breast reconstruction: pectoralis major myomammary flap versus
      DIEP and MS-2 TRAM.

PMID- 18060453
TI  - VR to OR: a review of the evidence that virtual reality simulation improves
      operating room performance.
AB  - The use of virtual reality (VR) simulation to train surgeons has been supported
      by a body of experimental data derived from randomized trials of VR simulation
      training versus no such training. These investigations have focused on the use of
      VR devices to train surgeons in laparoscopic and flexible endoscopic skills, and
      the studies have generally demonstrated that skills acquired through courses of
      training in VR transfer to the clinical or animal laboratory setting, where
      assessments of various types have been used to measure performance. These
      studies, as well as the study model that describes them, and the future of
      randomized trials of this type are reviewed.

PMID- 18060454
TI  - Percutaneous injection of lidocaine within the carotid body area in carotid
      artery stenting: an "old-new" technique.
AB  - Severe bradycardia is a common untoward effect during balloon angioplasty when
      performing carotid artery stenting. Therefore atropine injection even before
      dilatation and the presence of an anesthesiologist are advocated in all patients.
      In the surgical literature, injection of a local anesthetic agent into the
      carotid sinus before carotid endarterectomy was performed in an attempt to
      ameliorate perioperative hemodynamic instability. This study was undertaken to
      test the hypothesis that percutaneous infiltration of the carotid sinus with
      local anesthetic immediately before balloon dilatation reduces bradycardia and
      ameliorates the need for atropine injection or the presence of an
      anesthesiologist. Infiltration of the carotid sinus with 5 ml of 1% lidocaine, 3
      min before dilatation, was performed in 30 consecutive patients. No one exhibited
      any significant rhythm change that required atropine injection. The
      anesthesiologist did not face any hemodynamic instability during the carotid
      artery stenting procedure.

PMID- 18060455
TI  - The Amplatzer vascular plug also for ovarian vein embolization.

PMID- 18060456
TI  - Endovascular reconstruction of complex arterial obstructions in the mesenteric
      arcade with "kissing stents": technical note.
AB  - This report describes a technique for advanced endoluminal reconstruction of
      complex bifurcational arterial obstructions located within the mesenteric arcade
      deploying applications from percutaneous transluminal coronary artery
      angioplasty. A patient was treated for persistent mesenteric ischemia during
      prolonged recovery after initial small bowel resection due to acute mesenteric
      ischemia. Following endovascular reconstruction of a complex arterial obstruction
      within the mesenteric arcade, ischemic symptoms subsided quickly and the patient
      recovered well. According to the literature, this seems to be the first case
      where such distal reconstruction of the mesenteric arcade has successfully been
      achieved percutaneously.

PMID- 18060457
TI  - An intronic sequence mutated in flexed-tail mice regulates splicing of Smad5.
AB  - Recent work has identified a growing body of evidence that subtle changes in
      noncoding sequences can result in significant pathology. These mutations, which
      would have been called silent polymorphisms in the past, affect gene
      transcription and mRNA splicing and lead to drastic changes in gene expression.
      Previous work from our lab has characterized the murine flexed-tail (f) mutation,
      which encodes Smad5, a transcription factor that functions downstream of the
      receptors for bone morphogenetic proteins (BMPs). f/f mice are unable to rapidly
      respond to acute anemia. Our analysis of these mice led to the development of a
      new model for stress erythropoiesis, where BMP4 expression in the spleen leads to
      the Smad5-dependent expansion of a specialized population of stress erythroid
      progenitors during the recovery from acute anemia. f/f mutant mice exhibit a
      defect in Smad5 mRNA splicing in the spleen such that the majority of Smad5
      transcripts are two misspliced mRNAs. One of these mRNAs encodes a truncated form
      of Smad5 that inhibits BMP4 signaling when overexpressed. Here we show that a
      mutation in a poly(T) element in intron 4 causes the splicing defect in f/f
      mutant mice. This subtle mutation (loss of 1 or 2 Ts in a 16-T element) results
      in defects in splicing throughout the Smad5 gene. Furthermore, we show that this
      mutation results in tissue-specific splicing defects, which may explain why f/f
      mice are viable when Smad5-/- mice are embryonic lethal.

PMID- 18060459
TI  - Relationship between the endophyte Embellisia spp. and the toxic alkaloid
      swainsonine in major locoweed species (Astragalus and Oxytropis).
AB  - Locoweeds (Astragalus and Oxytropis spp. that contain the toxic alkaloid
      swainsonine) cause widespread poisoning of livestock on western rangelands. There
      are 354 species of Astragalus and 22 species of Oxytropis in the US and Canada.
      Recently, a fungal endophyte, Embellisia spp., was isolated from Astragalus and
      Oxytropis spp. and shown to produce swainsonine. We conducted a survey of the
      major locoweeds from areas where locoweed poisoning has occurred to verify the
      presence of the endophyte and to relate endophyte infection with swainsonine
      concentrations. Species found to contain the fungal endophyte and produce
      substantial amounts of swainsonine were A. wootoni, A. pubentissimus, A.
      mollissimus, A. lentiginosus, and O. sericea. Astragalus species generally had
      higher concentrations of swainsonine than Oxytropis. Swainsonine was not detected
      in A. alpinus, A. cibarius, A. coltonii, A. filipes, or O. campestris. The
      endophyte could not be cultured from A. mollissimus var. thompsonii or A.
      amphioxys, but was detected by polymerase chain reaction, and only 30% of these
      samples contained trace levels of swainsonine. Further research is necessary to
      determine if the endophyte is able to colonize these and other species of
      Astragalus and Oxytropis and determine environmental influences on its growth and
      synthesis of swainsonine.

PMID- 18060460
TI  - Modeling imatinib-treated chronic myelogenous leukemia: reducing the complexity
      of agent-based models.
AB  - We develop a model for describing the dynamics of imatinib-treated chronic
      myelogenous leukemia. Our model is based on replacing the recent agent-based
      model of Roeder et al. (Nat. Med. 12(10):1181-1184, 2006) by a system of
      deterministic difference equations. These difference equations describe the time
      evolution of clusters of individual agents that are grouped by discretizing the
      state space. Hence, unlike standard agent-base models, the complexity of our
      model is independent of the number of agents, which allows to conduct simulation
      studies with a realistic number of cells. This approach also allows to directly
      evaluate the expected steady states of the system. The results of our numerical
      simulations show that our model replicates the averaged behavior of the original
      Roeder model with a significantly reduced computational cost. Our general
      approach can be used to simplify other similar agent-based models. In particular,
      due to the reduced computational complexity of our technique, one can use it to
      conduct sensitivity studies of the parameters in large agent-based systems.

PMID- 18060458
TI  - Mammary cancer susceptibility: human genes and rodent models.
AB  - Breast cancer is a complex disease, showing a strong genetic component. Several
      human susceptibility genes have been identified, especially in the last few
      months. Most of these genes are low-penetrance genes and it is clear that
      numerous other susceptibility genes remain to be identified. The function of
      several susceptibility genes indicates that one critical biological pathway is
      the DNA damage response. However, other pathways certainly play a significant
      role in breast cancer susceptibility. Rodent models of breast cancer are useful
      models in two respects. They can help identify new mammary susceptibility genes
      by taking advantage of the very divergent susceptibilities exhibited by different
      mouse or rat strains and carrying out relevant genetic analyses. They also
      provide investigators with experimental systems that can help decipher the
      mechanism(s) of resistance to mammary cancer. Recent genetic and biological
      results obtained with mouse and especially with rat strains indicate that (1)
      numerous quantitative trait loci control mammary cancer susceptibility or
      resistance, with distinct loci acting in different strains, and (2) distinct
      resistance mechanisms operate in different rat resistant strains, precocious
      mammary differentiation being one of these mechanisms.

PMID- 18060461
TI  - Some elementary properties of SIR networks or, can i get sick because you got
      vaccinated?
AB  - We consider epidemics on social networks and address the question of whether
      administering a safe vaccine to one or more individuals can raise another
      individual's chances of becoming infected. Surprisingly, this can happen if
      transmission probabilities vary over time. If transmission probabilities do not
      vary with time, we show that in the discrete SIR model vaccination cannot cause
      collateral damage. We phrase this question in terms of monotonicity properties
      and answer it using bond percolation methods. By passing to a covering graph we
      are able to extend these results to models with more complicated latent and
      infective states.

PMID- 18060462
TI  - Asymptotic analysis and analytical solutions of a model of cardiac excitation.
AB  - We describe an asymptotic approach to gated ionic models of single-cell cardiac
      excitability. It has a form essentially different from the Tikhonov fast-slow
      form assumed in standard asymptotic reductions of excitable systems. This is of
      interest since the standard approaches have been previously found inadequate to
      describe phenomena such as the dissipation of cardiac wave fronts and the shape
      of action potential at repolarization. The proposed asymptotic description
      overcomes these deficiencies by allowing, among other non-Tikhonov features, that
      a dynamical variable may change its character from fast to slow within a single
      solution. The general asymptotic approach is best demonstrated on an example
      which should be both simple and generic. The classical model of Purkinje fibers
      (Noble in J. Physiol. 160:317-352, 1962) has the simplest functional form of all
      cardiac models but according to the current understanding it assigns a
      physiologically incorrect role to the Na current. This leads us to suggest an
      "Archetypal Model" with the simplicity of the Noble model but with a structure
      more typical to contemporary cardiac models. We demonstrate that the Archetypal
      Model admits a complete asymptotic solution in quadratures. To validate our
      asymptotic approach, we proceed to consider an exactly solvable "caricature" of
      the Archetypal Model and demonstrate that the asymptotic of its exact solution
      coincides with the solutions obtained by substituting the "caricature" right-hand
      sides into the asymptotic solution of the generic Archetypal Model. This is
      necessary, because, unlike in standard asymptotic descriptions, no general
      results exist which can guarantee the proximity of the non-Tikhonov asymptotic
      solutions to the solutions of the corresponding detailed ionic model.

PMID- 18060464
TI  - Voluntary and involuntary ligature of the bile duct in iatrogenic injuries: a
      nonadvisable approach.
AB  - BACKGROUND: Bile duct injuries related to laparoscopic and/or open
      cholecystectomy are a frequent finding and require surgical treatment. Complete
      obstruction is due to either intentionally or unintentionally placed ligatures or
      clips. The intentional application is usually performed to "facilitate
      identification of the duct by bile duct dilation." Considering that we are a
      national referral center for such injuries, we decided to analyze our cases of
      voluntary and involuntary duct ligation after iatrogenic bile duct injury.
      METHODS: We reviewed the files of patients with voluntary or involuntary bile
      duct ligation. Results of preoperative evaluation of the ducts, operative
      treatment, and postoperative results were analyzed. RESULTS: A total of 413
      patients were included. Forty-five patients presented with complete obstruction.
      In 15 cases, the ligature was intentional, and in 30 cases, occlusion was
      involuntary. Bile duct dilation (>10 mm) was demonstrated in one case of
      voluntary (6%) and three cases of involuntary ligations (10%). The remaining
      cases in both groups had no duct dilation and developed necrosis at the blinded
      duct and leakage proximal to the ligature, with different degrees of
      bilioperitoneum and/or biloma. In all cases, a Roux-en-Y hepatojejunostomy was
      performed. CONCLUSION: Bile duct ligature produces dilation in a very small
      number of patients (less than 10%) and usually produces necrosis of the blinded
      stump with subsequent bile leakage. Placement of a subhepatic drain and
      transference of the patient to a qualified center for reconstruction is the best
      approach if the primary surgeon is not able to do the repair.

PMID- 18060463
TI  - Under utilization of surveillance mammography among older breast cancer
      survivors.
AB  - BACKGROUND: Annual surveillance mammography is recommended for follow-up of women
      with a history of breast cancer. We examined surveillance mammography among
      breast cancer survivors who were enrolled in integrated healthcare systems.
      METHODS: Women in this study were 65 or older when diagnosed with early stage
      invasive breast cancer (N = 1,762). We assessed mammography use during 4 years of
      follow-up, using generalized estimating equations to account for repeated
      measurements. RESULTS: Eighty-two percent had mammograms during the first year
      after treatment; the percentage declined to 68.5% in the fourth year of follow
      up. Controlling for age and comorbidity, women who were at higher risk of
      recurrence by being diagnosed at stage II or receiving breast-conserving surgery
      (BCS) without radiation therapy were less likely to have yearly mammograms
      (compared to stage I, odds ratio [OR] for stage IIA 0.72, confidence interval
      [CI] 0.59, 0.87, OR for stage IIB 0.75, CI 0.57, 1.0; compared to BCS with
      radiation, OR 0.58, CI 0.43, 0.77). Women with visits to a breast cancer surgeon
      or oncologist were more likely to receive mammograms (OR for breast cancer
      surgeon 6.0, CI 4.9, 7.4, OR for oncologist 7.4, CI 6.1, 9.0). CONCLUSIONS:
      Breast cancer survivors who are at greater risk of recurrence are less likely to
      receive surveillance mammograms. Women without a visit to an oncologist or breast
      cancer surgeon during a year have particularly low rates of mammography.
      Improvements to surveillance care for breast cancer survivors may require active
      participation by primary care physicians and improvements in cancer survivorship
      programs by healthcare systems.

PMID- 18060465
TI  - Malignant melanoma of the gallbladder: a report of two cases and review of the
      literature.
AB  - Melanoma metastatic to the gallbladder is rare. When present, it is often part of
      a widespread complex of metastases. Primary gallbladder melanomas are also
      extremely rare and can sometimes be difficult to distinguish from metastatic
      lesions. The optimal treatment for malignant melanoma of the gallbladder remains
      unclear, and prognosis is generally poor. We present here two cases of patients
      with metastatic lesions to the gallbladder. One patient presented with
      symptomatic cholelithiasis and was found incidentally to have a metastasis.
      Another patient had known a metastasis, but underwent curative resection of the
      only site of disease. We review the published literature for gallbladder
      melanoma, both primary and metastatic to determine the role of surgery in this
      disease.

PMID- 18060466
TI  - Conservative management of adhesive small bowel obstructions in patients
      previously operated on for primary colorectal cancer.
AB  - This study aimed to determine the incidence of adhesive small bowel obstruction
      (SBO) after primary colorectal cancer surgery and the outcomes of conservative
      management using gastrointestinal tubes in such cases. Between October 2000 and
      December 2005, 2,586 primary colorectal cancer patients underwent consecutive
      operations and were followed up completely for a median of 38 months. During the
      follow-up periods, 119 patients with 130 consecutive cases of adhesive SBO
      underwent conservative management using nasogastric tubes and long intestinal
      tubes. The overall adhesive SBO rate was 5.0% in 38 months of follow-up, and the
      observed incidence rate was 0.0013 per patient-month. Of the 130 cases, 104 cases
      (80%) were successfully treated by conservative management, and the symptoms of
      SBO were resolved by the sixth day (range 1 to 22). Twenty-six cases (20%)
      underwent surgery because of lack of clinical improvement (17) or signs of
      strangulation (9). The high success rate indicates that initial conservative
      management with intestinal decompression using gastrointestinal tubes is
      recommended for patients with adhesive SBO after primary colorectal cancer
      surgery.

PMID- 18060467
TI  - Preoperative predictors for complications after pancreaticoduodenectomy: impact
      of BMI and body fat distribution.
AB  - BACKGROUND: The purpose of this study was to examine the preoperative patient and
      radiographic factors that are associated with operative morbidity after
      pancreaticoduodenectomy. MATERIAL AND METHODS: Patient characteristics and
      preoperative radiographic findings and their association with postoperative
      complications after pancreaticoduodenectomy were analyzed for 356 patients with
      pancreatic adenocarcinoma who underwent resection between 2000 and 2005. RESULTS:
      Postoperative complications developed in 135 patients (38%). The most common
      complications were pancreatic fistula/abscess (15%), wound infection (14%), and
      delayed gastric emptying (4%). On multivariate analysis, the only preoperative
      radiographic factors associated with having any postoperative complication were
      the absence of pancreatic atrophy and the extent of central obesity determined by
      the thickness of retrorenal visceral fat (VF). Complications occurred in 51% of
      patients with VF > or = 2 cm, compared to 31% of patients with VF < 2 cm, p <
      0.001. Postoperatively, pancreatic fistula developed in 24% of patients with VF >
      or = 2 cm and in only 10% of patients with VF < 2 cm, p = 0.01. Wound infections
      occurred in 21% of the patients with body mass index greater than or equal to 30
      kg/m(2) compared to 12% of the nonobese patients, p = 0.03. CONCLUSIONS:
      Generalized obesity is associated with postoperative wound infections after
      pancreaticoduodenectomy. The degree of visceral fat on preoperative cross
      sectional imaging is associated with significantly higher rates of overall
      complications and pancreatic fistula.

PMID- 18060468
TI  - Right portal vein ligation is as efficient as portal vein embolization to induce
      hypertrophy of the left liver remnant.
AB  - BACKGROUND: Aim of this retrospective study was to compare induction of left
      liver hypertrophy after right portal vein ligation (PVL) and right portal vein
      embolization (PVE) before right hepatectomy for liver metastases. MATERIALS AND
      METHODS: Between 1998 and 2005, 18 patients underwent a PVE, whereas 17 patients
      underwent a PVL during a first stage laparotomy. RESULTS: There was no
      complication related to PVE or PVL. After a similar interval time (7 +/- 3 vs 8
      +/- 3 weeks), the increase of the left liver volume was similar between the two
      groups (35 +/- 38 vs 38 +/- 26%). After PVE and PVL, right hepatectomy was
      performed in 12 and 14 patients, respectively. Technical difficulties during the
      right hepatectomy were similar according to duration of procedure (6.4 +/- 1 vs
      6.7 +/- 1 h, p = 0.7) and transfusion rates (33 vs 28%, p = 0.7). Mortality was
      nil in both groups, and morbidity rates were respectively 58% for the PVE group
      and 36% for the PVL group (p = 0.6). CONCLUSION: Right PVL and PVE result in a
      comparable hypertrophy of the left liver. During the first laparotomy of a two
      step liver resection, PVL can be efficiently and safely performed.

PMID- 18060469
TI  - Utility of divided omentum for preventing complications associated with
      laparoscopic gastric bypass.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass has emerged as a standard
      surgical treatment for morbid obesity. However, prevention of postoperative
      complications associated with bariatric surgery is an important consideration.
      METHODS: To reduce postoperative complications and achieve adequate body weight
      loss, we introduce a simple procedure using a divided omentum during laparoscopic
      Roux-en-Y gastric bypass. The actual aim of this procedure is to prevent leakage
      from the gastric pouch or anastomosis and the gastro-gastric fistula because of
      reentry of the alimentary tract. Between February 2002 and April 2007, we
      performed laparoscopic Roux-en-Y gastric bypass for morbid obesity in 94
      patients. In the most recent 83 cases, our simple procedure using a divided
      omentum was employed. RESULTS: These patients comprised 20 males and 63 females,
      with a mean age of 38 years, and a mean body mass index of 44.1 kg/m(2). At
      surgery, the omentum is routinely divided using laparoscopic coagulating shears
      before performing gastrojejunostomy to reduce the tension on the anastomosis
      caused by the route of reconstruction. After performing hand-sewn
      gastrojejunostomy, the left side of the divided omentum is moved cranially and
      interposed between the gastric pouch and the excluded stomach. The omentum is
      then sutured from the posterior aspect of the gastric pouch to the anterior side
      of the anastomosis. CONCLUSION: Our procedure using a divided omentum during
      bariatric surgery is feasible and safe for obtaining better outcomes without
      artificial materials. Although the long-term outcome of this technique is still
      unclear, we believe that it will contribute to decreasing the particular
      complications related to laparoscopic Roux-en-Y gastric bypass for morbid
      obesity.

PMID- 18060470
TI  - An attempt to measure the spread of emergency medicine internationally.
AB  - OBJECTIVE: To determine the feasibility of using the internet to track the spread
      of emergency medicine internationally. METHODS:  OVERVIEW: This was an attempt to
      perform a descriptive cross-sectional study employing a web-based survey.
      SUBJECTS: Potential respondents were identified from multiple sources.
      OBSERVATIONS: The primary outcome was the response to 16 questions about EM care
      and the setting in which it was delivered for acute cardiac, paediatric,
      obstetrical illnesses and trauma. The questions were divided into six general
      areas and elicited for urban, semi-urban and rural settings. A series of four e
      mails soliciting completion of the survey were sent to potential respondents.
      ANALYSIS: Simple descriptive statistics. RESULTS: We identified 358 potential
      respondents with valid e-mail addresses over a period of three years. Overall,
      145 (41%) responded and 117 (33% 95% CI 28-38%) of them were complete and
      interpretable. There was one response from 54 and two responses from 29
      countries, representing an overall response rate by country surveyed of 65% (95%
      CI 57-73%), but of all existing countries of only 43% (95% CI 36-50%). Based on
      sparse data, it appears that in urban areas, 47% (obstetrics) to 65% (paediatric)
      of acutely sick or injured patients are taken to an ED-equivalent. For rural
      areas, this range was 19% (obstetrical) to 40% (trauma). CT scans are available
      in 78% of urban ED-equivalents but 12% of rural ones. Haematocrits are available
      in 72% of rural settings. In 60% of responding nations, some type of EM training
      was available, and in 42% physicians went abroad to study EM. CONCLUSIONS: A
      survey of international EM is challenging to achieve because of difficulty in
      both identifying and in contacting potential respondents. Based on sparse data,
      population density (urban, rural) appears to be related to both the location to
      which acutely ill patients are taken for their care and to the level of
      technology available. The specialty of EM is now recognised internationally and
      education in EM is common.

PMID- 18060472
TI  - Features of ceruloplasmin in the cerebrospinal fluid of Alzheimer's disease
      patients.
AB  - The level of the apo-form of the copper enzyme ceruloplasmin (CP) is an
      established peripheral marker in diseases associated with copper imbalance. In
      view of the proposal that disturbances of copper homeostasis may contribute to
      neurodegeneration associated with Alzheimer's disease (AD), the present work
      investigates, by Western blot and non-reducing SDS-PAGE followed by activity
      staining, the features of CP protein, and the copper/CP relationship in
      cerebrospinal fluid (CSF) and serum of AD patients. Results show that only a
      fraction of total copper is associated with CP in the CSF, at variance with
      serum, both in affected and in healthy individuals. Furthermore, a conspicuous
      amount of apo-ceruloplasmin and a decrease of CP oxidase activity characterize
      the CSF of the affected individuals, and confirm that an impairment of copper
      metabolism occurs in their central nervous system. In the CSF of AD patients the
      decrease of active CP, associated with the increase in the pool of copper not
      sequestered by this protein, may play a role in the neurodegenerative process.

PMID- 18060471
TI  - Epidemiology of colorectal cancer: the 21-year experience of a specialised
      registry.
AB  - Cancer registries can be viewed as one of the main strategies for improving our
      understanding of cancer, as they may reveal the importance of specific trends in
      cancer incidence and survival; in addition, the information obtained from the
      registries can be translated into preventive measures that might lead to a better
      control of neoplasms. A colorectal cancer registry was instituted in Northern
      Italy in 1984. The purpose of this study is to provide a description of the main
      findings observed in a 21-year period of continuous registration. RESULTS: A
      total of 3951 malignancies of the large bowel were registered in 3817 patients,
      for a crude incidence rate of 75.1/100 000/year in men and 59.0 in women. Overall
      incidence (crude and age-adjusted) of colorectal tumours increased remarkably
      throughout the registration period. This increase was mainly due to early (Stage
      I and II) tumours and to lesions with lymph nodal involvement (Stage III). There
      was a tendency over time towards a progressive increase of colonic tumours,
      whereas the fraction of rectal neoplasms tended to decline. Colorectal cancer
      specific survival increased significantly over time in each of the main TNM/Dukes
      classes (p<0.006 and <0.001 for Stage II and III tumours). Finally, surgery for
      colorectal tumours showed a tendency towards large operations (colectomy and
      hemicolectomy), which was parallel to a definite improvement of pathological
      staging. CONCLUSIONS: Despite the increasing incidence of colorectal cancer,
      there are several reasons for cautious optimism. Most of the lesions are now
      diagnosed at an early stage, and this is associated with a significant increase
      of survival. The disease is undoubtedly cured better than in the past; the main
      challenge for future years is to achieve a sustained reduction of mortality for
      colorectal neoplasms.

PMID- 18060473
TI  - Chelerythrine treatment influences the balance of pro- and anti-apoptotic
      signaling pathways in the remote myocardium after infarction.
AB  - OBJECTIVE: Apoptotic processes may be implicated in the molecular pathomechanisms
      of ventricular remodeling after myocardial infarction (MI). The modulation of
      apoptosis by pro- and anti-apoptotic pathways in the myocardium remote from the
      infarction, including its link to protein kinase C (PKC), was focus of the
      present study. METHODS: Rats were subjected to MI by LAD ligation in situ. Some
      animals were pretreated with the PKC inhibitor chelerythrine. After 1 h up to 28
      days, pro- and anti-apoptotic signals (caspase-3, Bcl-2/Bax ratio, Akt, Bad), and
      marker of apoptosis execution (DNA laddering, TUNEL) were quantified in the
      myocardium remote from the infarction. RESULTS: Activation of caspase-3, a pro
      apoptotic shift of the Bcl-2/Bax ratio, and DNA fragmentation were observed as
      early as 3 h after infarction and persisted up to 28 days. Akt- and Bad
      phosphorylation was unchanged. Chelerythrine markedly reduced DNA fragmentation.
      Caspase-3 activation was unchanged. Surprisingly, Bad and Akt phosphorylation
      were highly increased (180% and 750% of control). CONCLUSION: Chelerythrine
      influences the balance of pro- and anti-apoptotic pathways in the remote
      myocardium after infarction, with an inhibition of proapoptotic and an activation
      of anti-apoptotic signals.

PMID- 18060474
TI  - Induction of apoptosis by hydrogen peroxide in HPV 16 positive human cervical
      cancer cells: involvement of mitochondrial pathway.
AB  - Cervical cancer is the second most common malignant neoplasm in women, in terms
      of incidence and mortality rates worldwide, and is associated with excessive
      inflammation. This involves the expression of both pro- and anti-apoptotic
      proteins that have varied effect on tumor growth and metastasis. The objective of
      the present study was to elucidate the effect of hydrogen peroxide (H2O2) on
      apoptotic signal molecules in vitro in SiHa and CaSki cell lines expressing the
      human papilloma virus 16 E6 protein, which causes the ubiquitin-mediated
      degradation of p53 protein and is thus p53 deficient. The p53 is known to act as
      a cellular stress sensor and triggers apoptosis. We demonstrate, here, that in
      HPV 16 positive cell lines apoptosis is triggered by upregulation of p73, which
      causes activation of pro-apoptotic Bax accompanied by down regulation of anti
      apoptotic Bcl xl, release of cytochrome c from mitochondria and activation of
      caspases-9 and -3.

PMID- 18060476
TI  - Critical role of phosphoinositide 3-kinase cascade in adipogenesis of human
      mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent stem cells capable of
      differentiating into adipocytes in the presence of a hormone cocktail. These
      cells thus provide a promising model for studying the early events of
      adipogenesis. Here, we examine the involvement of the PI3K/Akt and mTOR/p70S6K
      signaling pathways in human MSC adipogenesis. We found that the two pathways were
      strongly activated with a similar temporal profile under the adipogenesis
      inducing hormone cocktail and this activation could be blocked by LY294002, a
      specific inhibitor of PI3K. Furthermore, rapamycin, a specific inhibitor of mTOR,
      blocked the activation of mTOR/p70S6K but not PI3K/Akt. Both LY294002 and
      rapamycin severely suppressed lipid accumulation, as well as the expression of
      adipogenic markers, including PPAR gamma 2 and C/EBP alpha, two master adipogenic
      transcription factors. Together, these data indicate that the mTOR/p70S6K pathway
      acts downstream of the PI3K/Akt pathway in mediating the adipogenic conversion of
      MSCs. In conclusion, our data suggest that the PI3K/Akt and mTOR/p70S6K signaling
      pathways are essential for adipogenesis of human MSCs.

PMID- 18060475
TI  - Caffeic acid phenethyl ester induces mitochondria-mediated apoptosis in human
      myeloid leukemia U937 cells.
AB  - Caffeic acid phenyl ester (CAPE), a biologically active ingredient of propolis,
      has several interesting biological properties including antioxidant, anti
      inflammatory, antiviral, immunostimulatory, anti-angiogenic, anti-invasive, anti
      metastatic and carcinostatic activities. Recently, several groups have reported
      that CAPE is cytotoxic to tumor cells but not to normal cells. In this study, we
      investigated the mechanism of CAPE-induced apoptosis in human myeloid leukemia
      U937 cells. Treatment of U937 cells with CAPE decreased cell viability in a dose
      dependent and time-dependent manner. DNA fragmentation assay revealed the typical
      ladder profile of oligonucleosomal fragments in CAPE-treated U937 cells. In
      addition, as evidenced by the nuclear DAPI staining experiment, we observed that
      the nuclear condensation, a typical phenotype of apoptosis, was found in U937
      cells treated with 5 microg/ml of CAPE. Therefore, it was suggested that CAPE is
      a potent agent inducing apoptosis in U937 cells. Apoptotic action of the CAPE was
      accompanied by release of cytochrome C, reduction of Bcl-2 expression, increase
      of Bax expression, activation/cleavage of caspase-3 and activation/cleavage of
      PARP in U937 cells, but not by Fas protein, an initial mediator in the death
      signaling, or by phospho-eIF2 alpha and CHOP, crucial mediators in ER-mediated
      apoptosis. From the results, it was concluded that CAPE induces the mitochondria
      mediated apoptosis but not death receptors- or ER-mediated apoptosis in U937
      cells.

PMID- 18060477
TI  - Injectability evaluation of tricalcium phosphate bone cement.
AB  - Calcium phosphate cements are biomaterials made from a mixture of calcium
      phosphate powder in aqueous solutions that forms a paste that reacts at the body
      temperature and hardens as a result of precipitation reactions. These cements are
      commonly used in dentistry and orthopedic bone filling surgeries, which require
      extremely invasive procedures. The challenge consists in formulating an
      injectable paste by additives incorporation. In this work, three different
      additives (carboxymethylcellulose, agar polymer and sodium alginate) were
      incorporated to tricalcium phosphate, in concentrations of 0.4, 0.8, 1.6, 3.2 and
      6.4 wt.%. Injectability was evaluated through a new method developed for this
      purpose. Results showed that it was possible to obtain injectable compositions of
      alpha-tricalcium phosphate cement. It was verified that the injectability depends
      on the rheological behavior of the pastes and injection time. In this study,
      pastes with viscosity suitable for good homogenization and injection were
      obtained.

PMID- 18060478
TI  - The preparation of high conversion polymeric systems containing eugenol residues
      and their rheological characterization.
AB  - Copolymeric systems bearing eugenol covalently linked to the macromolecular
      chains have been prepared and characterised in terms of thermal, rheological and
      in vitro behaviour. Eugenyl methacrylate (EgMA) and ethoxyeugenyl methacrylate
      (EEgMA) were polymerized and copolymerized with ethyl methacrylate (EMA) in a
      wide range of feed composition by bulk at high conversion. Glass transition
      temperature (Tg) increased with the content of EgMA in the copolymer whereas Tg
      decreased with the content of EEgMA. The presence of any of the eugenyl monomers
      in the copolymer increased the thermal stability of the materials. Rheological
      analysis showed that EMA-co-EgMA copolymers present a higher density of
      crosslinking or entanglements among the chains compared with EMA-co-EEgMA
      materials, and copolymers containing more than 40% EgMA exhibited a pseudo-solid
      like behaviour with G' relatively independent of the frequency. The average
      molecular weight between cross-links (Mc) for the latter copolymers was in the
      order of 10(4) Da. For EEgMA copolymers, tan delta was lower than unity and G'
      showed a gradual and slight dependency with frequency over the whole range of
      composition. In vitro behaviour showed a higher hydrophilicity of the EEgMA
      containing copolymers manifested in higher water sorption values, lower water
      contact angle values and higher surface free energy due to an increase in
      polarity. All systems presented a good cytocompatibility with human fibroblasts
      assessed through direct and indirect assays.

PMID- 18060479
TI  - Processing, characterisation, and biocompatibility of zinc modified metaphosphate
      based glasses for biomedical applications.
AB  - Bulk and structural properties of zinc oxide (0 up to 20 mol%) containing
      phosphate glasses, developed for biomedical applications, were investigated
      throughout this study using differential thermal analysis (DTA), differential
      scanning calorimetry, X-ray powder diffraction and 31P and 23Na MAS NMR. Surface
      wettability and MG63 viability were also considered for surface characterisation
      of these glasses. The results indicated that incorporation of zinc oxide as a
      dopant into phosphate glasses produced a significant increase in density;
      however, the thermal properties presented in glass transition, and melting
      temperatures were reduced. NaZn(PO3)3 was detected in the X-Ray Powder
      Diffraction Analysis (XRD) trace of zinc containing glasses, and the proportion
      of this phase increased with increasing zinc oxide content. NaCa(PO3)3 as a
      second main phase and CaP2O6 in minor amounts were also detected. The 31P and
      23Na MAS NMR results suggested that the relative abundances of the Q1 and Q2
      phosphorus sites, and the local sodium environment were unaffected as CaO was
      replaced by ZnO in this system. The replacement of CaO with ZnO did seem to have
      the effect of increasing the local disorder of the Q2 metaphosphate chains, but
      less so for the Q1 chain-terminating sites which were already relatively
      disordered due to the proximity of modifying cations. Glasses with zinc oxide
      less than 5 mol% showed higher surface wettability, while those with 5 up to 20
      mol% showed comparable wettability as zinc oxide free glasses. Regardless of the
      high hydrophilicity and surface reactivity of these zinc oxide containing
      glasses, they had lower biocompatibility, in particular 10-20 mol% ZnO, compared
      to both zinc free glasses and Thermanox. This may be associated with the release
      of significant amount of Zn2+ enough to be toxic to MG63.

PMID- 18060480
TI  - Experimental investigations for mechanical joint strength following
      ultrasonically welded pin osteosynthesis.
AB  - The purpose of this study was to determine whether fixation of cranial bone
      segments using ultrasonically welded pin osteosynthesis showed differences in
      mechanical stability as compared to fixation of cranial bone segments using screw
      osteosynthesis. Right and left cranial bone segments from each of 16 young sheep
      were obtained by craniotomy and re-fixed: on the right with a mesh plate and
      pins, and on the left with a mesh plate and screws. All osteosynthesis materials
      consisted of PDLLA, fully amorphous polyactid. A total of 167 cranial bone / mesh
      plate segments from 16 animals were investigated; 84 segments were pin-fixed and
      83 segments were screw-fixed. The implantation time of the re-fixed segments
      ranged from 1 day to 196 days. The mechanical methods chosen for simulation of
      stress on the bone segment bonds were two bending tests (horizontal and vertical
      directions) and a tensile test. The values obtained in the mechanical tests
      indicate differences in the bond strength between the pin- and screw- fixation
      methods over the length of in vivo implantation time. The mechanical stability of
      the ultrasonically welded pin osteosynthesis bonds over the screw osteosynthesis
      bonds proved to be statistically significant. The implication of these findings
      should also be relevant in the field of medicine.

PMID- 18060481
TI  - Toxicological protein biomarker analysis--an investigative one-week single dose
      intravenous infusion toxicity and toxicokinetic study in cynomolgus monkeys using
      an antibody-cytotoxic conjugate against ovarian cancer.
AB  - INTRODUCTION: Antibody-cytotoxic conjugates are complex novel therapeutic agents
      whose toxicological properties are not presently well understood. The objective
      of this study was to identify toxicological markers in serum that correlate with
      MLN8866 (an antibody-cytotoxic conjugate) exposure and related pathological
      events in monkeys. MATERIALS AND METHODS: Cynomolgus monkeys were treated once
      with 5, 15, or 30 mg/kg MLN8866 via a 20 min intravenous infusion. MLN8866
      exposure (Cmax and AUCO-4 day) was determined by quantifying MLN8866 levels in
      serum. RESULTS: The increase in MLN8866 exposure was approximately dose
      proportional. Two acute phase proteins in serum (serum amyloid A and haptoglobin)
      were correlated with MLN8866 exposure and toxicological outcomes (e.g.,
      erythropoiesis and leucopoiesis).

PMID- 18060482
TI  - Spectral properties of probes containing benzothioxanthene chromophore linked
      with hindered amine in solution and in polymer matrices.
AB  - Absorption and emission spectroscopy as well as laser flash photolysis was
      employed in order to characterize the spectral properties of novel probes based
      on benzothioxantheneimide chromophore covalently linked with different types of
      sterically hindered amines. These were chosen as 2-(2,2,6,6-tetramethyl-4
      piperidyl)-thioxantheno[2,1,9-dej]isoquinoline-1,3-dione (BTXINH), the equivalent
      stable nitroxyl radical, i.e. 2-(1-oxo-2,2,6,6-tetramethyl-4
      piperidyl)thioxantheno[2,1,9dej]isoquinoline 1,3-dione (BTXINO) and the alkoxy
      derivative 2-(1-(1'-phenylethoxy)-2,2,6,6-tetramethyl-4-piperidyl)
      thioxantheno[2,1,9-dej]isoquinoline-1,3-dione (BTXINOR). Spectral properties, in
      solutions and in various polymer matrices such as polystyrene, polymethyl
      methacrylate, polyvinyl chloride and polypropylene, were compared with the
      compound 2-(1-dodecyl)-thioxantheno[2,1,9-dej]isoquinoline-1,3-dione (BTXID)
      taken in the present study as a reference compound. By means of the fluorescence
      decay and in the contrary to three other probes, BTXINO probe clearly showed a
      biexponential decay while the three other probes led to monoexponential decay.
      Two different singlet excited states with lifetimes of about 0.4 and 5 ns were
      proposed. They correspond to two dispositions of the nitroxyl radical chain above
      and along the fluorescent moiety of the molecule. Such behaviour depends on the
      surrounding media. Moreover, an efficient intramolecular quenching of the
      fluorescence emission was only observed with the short lived singlet excited
      state. The ratio BTXID/BTXINO was found equal to about 4 and 9 in solutions and
      polymer matrices respectively. Laser flash photolysis indicated that the novel
      probes as well as the model compound yielded transient absorption with maximum at
      530 nm, corresponding to the triplet states. The intermolecular quenching of such
      species by molecular oxygen and by free N-oxyl, such as 1-oxy-2,2,6,6
      teramethylpiperidine (TEMPO) and 1-oxy-2,2,6,6-teramethyl-4-hydroxypiperidine
      (TEMPOL), and the intramolecular quenching was not efficient.

PMID- 18060483
TI  - Under the microscope.
AB  - This is a personal account of life in the United Kingdom National Health Service
      by a pathologist who has worked there for 25 years. The principles of clinical
      governance are embraced by the medical profession, but their application is often
      insensitive, governmental and bureaucratic. A doctor's working life is now less
      autonomous, less centred on the patient and less fun. Medical humanities are a
      balm for the sore spots but not, I think, used consciously so by management,
      likely suffering from the same bureaucratic governmentality that sees value in
      nothing-unless it can be measured.

PMID- 18060485
TI  - Maternal breastfeeding attitudes: association with breastfeeding intent and socio
      demographics among urban primiparas.
AB  - Breastfeeding is associated with improved developmental and social outcomes for
      an infant. Despite these health benefits, only 54% of women breastfeed in the
      early postpartum period. Although an understanding of socio-demographic
      characteristics, breastfeeding intent, and breastfeeding attitudes can facilitate
      breastfeeding initiatives, these factors have not been characterized particularly
      for urban and immigrant mothers. The objectives of this study are to provide a
      descriptive analysis of the socio-demographic characteristics, breastfeeding
      intent, and breastfeeding attitudes of primiparas presenting to an inner city
      prenatal clinic and determine if breastfeeding attitudes are associated with
      breastfeeding intent and socio-demographic variables. Of 100 primiparas, 79
      reported the intent to breastfeed. Breastfeeding intent was associated with 1)
      positive breastfeeding attitudes, 2) higher household incomes, 3) being born
      outside the US, 4) being Afro-Caribbean as opposed to African American, 5) having
      family, peer, and partner support for breastfeeding, 6) attending breastfeeding
      classes, and 7) greater years of education. These findings suggest that targeting
      breastfeeding initiatives towards low-income, less educated, US born mothers who
      lack breastfeeding support from their loved ones may improve breastfeeding rates
      among urban primiparas.

PMID- 18060486
TI  - Investigating investigators: examining the impact of eyewitness identification
      evidence on student-investigators.
AB  - This research examined the impact of eyewitness identification decisions on
      student-investigators. Undergraduates played the role of police investigators and
      interviewed student-witnesses who had been shown either a good or poor view of
      the perpetrator in a videotaped crime. Based on information obtained from the
      witness, student-investigators then chose a suspect from a database containing
      information about potential suspects and rated the probability that their suspect
      was the culprit. Investigators then administered a photo lineup to witnesses, and
      re-rated the probability that their suspect was guilty. Student-investigators
      were highly influenced by eyewitness identification decisions, typically
      overestimating the information gained from the identification decision (except
      under conditions that led witnesses to be very accurate), and were generally
      unable to differentiate between accurate and inaccurate witnesses.

PMID- 18060487
TI  - Analyzing the performance of risk assessment instruments: a response to Vrieze
      and Grove (2007).
AB  - In a recent article, Vrieze and Grove (Law Hum Behav, doi: 10.1007/s10979-007
      9092-x , 2007) argue that, because of low recidivism base rates and limited
      predictive accuracy, an actuarial risk assessment instrument (ARAI) may produce
      decisions about sex offenders that are worse than simply predicting that no one
      will commit another sex offense. This article examines: (1) the construction and
      potential overfitting of ARAIs; (2) the meaning, value, and limitations of ROC
      areas; and (3) the relationship between the operating point that maximizes an
      ARAI's correct classifications and the legal criterion-"likely to reoffend"-used
      for sex offender designations. Contrary to what Vrieze and Grove suggest, ARAIs
      of modest accuracy yield probabilistic information that is more relevant to legal
      decision-making than just "betting the base rate."

PMID- 18060488
TI  - Impact of child disability on the family.
AB  - Families with disabled children represent a sizeable share of all American
      households. Living with a disabled child can have profound effects on the entire
      family, which in turn can affect the health and well-being of the child who is
      disabled. Much needs to be learned about how children's health affects their
      parents, siblings, and other family members and about how family characteristics
      and resources modify those associations. Numerous programs and organizations
      provide resources for disabled children and their families, but the system is
      extremely fragmented and difficult to navigate. This commentary reviews what is
      known about the effects of child disability on the family, provides an overview
      of the complex needs of and multitude of resources available to families of
      disabled children, and concludes with suggested directions for practice,
      research, and public policy.

PMID- 18060489
TI  - Lateral dendritic shunt inhibition can regularize mitral cell spike patterning.
AB  - Mitral cells, the principal output neurons of the olfactory bulb, receive direct
      synaptic activation from primary sensory neurons. Shunting inhibitory inputs
      delivered by granule cell interneurons onto mitral cell lateral dendrites, while
      poorly positioned to prevent spike initiation, are believed to influence spike
      timing and underlie coordinated field potential oscillations. We investigated
      this phenomenon in a reduced compartmental mitral cell model suitable for
      incorporation into network simulations. Lateral dendritic shunt conductances
      delayed spiking to a degree dependent on both their electrotonic distance and
      phase of onset. Moreover, when the afferent activation of mitral cells was
      loosely coordinated in time, recurrent inhibition significantly narrowed the
      distribution of mitral cell spike times, illustrating a tendency towards
      coordinated synchronous activity. However, if mitral cell activity was initially
      disorganized, recurrent inhibition actually increased the variance in spike
      timing. This result suggests an essential role for early mechanisms of temporal
      coordination in olfaction, such as sniffing and the initial synchronization of
      mitral cell intrinsic oscillations by periglomerular cell-mediated inhibition.

PMID- 18060491
TI  - Identification of a novel BRCA1 large genomic rearrangement in a Spanish
      breast/ovarian cancer family.
AB  - BACKGROUND: Alterations in BRCA1 gene are responsible for the majority of
      hereditary breast and/or ovarian cancers. However, the frequency of detected
      germline mutations is lower than expected by linkage analysis. Standard PCR-based
      screening methods are mainly used for detecting mutations, but the large genomic
      rearrangements are commonly overlooked. The purpose of this study was to confirm
      and characterize a novel deletion identified in BRCA1 gene which has not yet been
      reported to date. METHODS: Multiplex ligation-dependent probe amplification was
      used to analyze BRCA1 rearrangements in 255 unrelated index patients with
      familial breast and/or ovarian cancer negative for BRCA1/BRCA2 mutations studied
      in Program of Genetic Counselling on Cancer of Valencia Community (Spain). The
      breakpoints of detected novel rearrangement were characterized by sequencing.
      RESULTS AND DISCUSSION: Five different rearrangements in the BRCA1 gene were
      identified in five unrelated index patients out of the 225 (2%). We found four
      large genomic rearrangements already described consisting in a 1A/1B and 2
      deletion; deletion of exons 5-7; deletion of exons 8-13; exon 20 deletion.
      Additionally, we found the novel g.8097_22733del14637 deletion that encompasses
      exons 3-5. This deletion affects the RING domain of the BRCA1 protein and it is
      suggestive of having a negative impact on its function. CONCLUSION: The new
      mutation here reported broadens the mutational spectrum of large rearrangements.
      Furthermore, the five large rearrangements found in patients non-carriers of
      BRCA1/BRCA2 mutations reinforce the need of studying BRCA1 large genomic
      rearrangements in genetic counselling programs.

PMID- 18060492
TI  - Breast cancer cells with acquired resistance to the EGFR tyrosine kinase
      inhibitor gefitinib show persistent activation of MAPK signaling.
AB  - Although the epidermal growth factor receptor (EGFR) is frequently expressed in
      human primary breast carcinoma, the majority of breast cancer patients do not
      respond to treatment with EGFR tyrosine-kinase inhibitors such as gefitinib. We
      isolated through a stepwise dose escalation of the drug two gefitinib-resistant
      SK-Br-3 clones, ZD6 and ZD10 (ZD) cells, which showed, respectively, a three- to
      five-fold increase in the IC50 for gefitinib as compared with parental cells. The
      levels of expression of EGFR were increased in ZD cells as compared with wild
      type SK-Br-3 cells. The phosphorylation of EGFR, ErbB-2, ErbB-3 and Akt was
      significantly reduced in gefitinib-resistant cells. In contrast, ZD cells showed
      levels of MAPK phosphorylation similar to untreated wild-type cells when cultured
      in presence of gefitinib. Persistent activation of MAPK was also observed in
      gefitinib-resistant clones isolated from MDA-MB-175 and MDA-MB-361 breast cancer
      cell lines. ZD cells showed an increased sensitivity to the MEK inhibitor PD98059
      as compared with SK-Br-3 cells, and a synergistic anti-tumor effect was observed
      when ZD cells were treated with a combination of gefitinib and PD98059.
      Overexpression of a constitutively activated form of p42-MAPK in SK-Br-3 cells
      resulted in an approximately 50% increase in the IC50 to gefitinib. Finally,
      culture of ZD10 resistant cells in absence of gefitinib led to reversion of the
      resistant phenotype. These observations suggest that MAPK signaling might play a
      role in the resistance that develops in breast cancer cells after long-term
      exposure to gefitinib.

PMID- 18060493
TI  - Routine prophylactic granulocyte colony stimulating factor (GCSF) is not
      necessary with accelerated (dose dense) paclitaxel for early breast cancer.
AB  - BACKGROUND: Prophylactic granulocyte colony stimulating factor (GCSF) is
      recommended with accelerated adjuvant chemotherapy but is expensive and causes
      bone pain. We have reviewed a series of patients with early breast cancer treated
      with accelerated 2-weekly paclitaxel without routine GCSF to assess its need.
      PATIENTS AND METHODS: Patients receiving accelerated (dose dense) paclitaxel 175
      mg/m2 2 weekly for 4 courses as adjuvant/neoadjuvant treatment for early breast
      cancer were treated electively without prophylactic GCSF, and monitored for
      absolute neutrophil count (ANC) before each cycle, grade and duration of
      neutropenia, incidence of neutropenic sepsis, treatment delays and requirements
      for secondary GCSF. Results were compared with prior patients given prophylactic
      GCSF. RESULTS: Of the 61 patients, 42 (69%) did not require prophylactic GCSF.
      Mild/moderate neutropenia was more common than in the prior group given GCSF, but
      secondary GCSF was required in only 6 (10%) patients due to grade 3 neutropenia
      and in 12 (20%) with grade 2 neutropenia. There were no episodes of neutropenic
      sepsis and no dose reduction or treatment delay was required. CONCLUSIONS:
      Accelerated paclitaxel in breast cancer patients without prophylactic GCSF is
      safe, avoids side effects, reduces costs and is not associated with an increase
      risk of neutropenic sepsis or treatment delays.

PMID- 18060494
TI  - Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or ovarian
      cancer families of Eastern Spain.
AB  - It is well established that mutations in BRCA1 and BRCA2 genes significantly
      increase the risk of breast and ovarian cancer. We here report 23 novel genetic
      variants of the BRCA1 and BRCA2 genes found in 349 cancer-prone unrelated
      families from Eastern Spain detected during the first 2 years of performance of
      the Program of Genetic Counseling of Valencia Community. Mutational screening was
      performed by pre-screening the heteroduplex formed in the PCR products obtained
      amplifying BRCA1 and BRCA2 genes by conformation sensitive electrophoresis. We
      detected 10 deletereous mutations, four in BRCA1 (three frame-shift (FS) and one
      nonsense mutation (NS)) and six in BRCA2 (four FS and one NS mutation). Moreover,
      we detected 13 unclassified variants, four in BRCA1 (one missense (MS), two
      synonymous (SYN) and one intronic (I) variant) and nine in BRCA2 (six MS, one SYN
      and two I). The relevance of the novel mutations is discussed. Our contribution
      broadens the BRCA1/2 world mutational spectra.

PMID- 18060495
TI  - Is single-cell apoptosis sufficient for the diagnosis of graft-versus-host
      disease in the colon?
AB  - Low-grade lesions of graft-versus-host disease (GVHD) in the colon are not
      uncommon. To determine if minimal diagnostic criteria can be established in such
      biopsies, we correlated histologic findings with clinical history and
      investigated the role of endoscopy and electron microscopy in establishing GVHD.
      About 85 colonic biopsies that were histologically consistent with GVHD from 47
      bone-marrow transplant recipients were reviewed retrospectively. Of nine cases
      showing only a single apoptotic cell in the intestinal epithelium, only four
      lacked any confounding factors of GVHD. These cases, while too few to assess the
      utility of finding one apoptotic cell with statistical significance, appear to
      support the idea that in the appropriate clinical setting, a single apoptotic
      cell could be reported as possibly representing early GVHD. Endoscopic findings
      did not reliably correlate with histology. Although electron microscopy can be a
      useful adjunct, it does not contribute to the diagnosis of GVHD.

PMID- 18060496
TI  - A unique presentation: dorsal agenesis of the pancreas manifesting as pancreatic
      exocrine insufficiency in the absence of diabetes mellitus in an 8-year-old boy.

PMID- 18060497
TI  - Abuse in women and men with and without functional gastrointestinal disorders.
AB  - We aimed to investigate the history of abuse in childhood and adulthood and
      health-related quality of life (HRQL) in women and men with FGID in the general
      adult population. A cross-sectional study in a random population sample (n =
      1,537, 20-87 years) living in Osthammar municipality, Sweden, in 1995 was
      performed. Persons with FGID (n = 141) and a group of abdominal symptom-free
      controls (SSF, n = 97) were selected by means of a validated questionnaire
      assessing gastrointestinal symptoms (the ASQ). Abuse, anxiety and depression (the
      HADS) and HRQL (the PGWB) were measured. Women with FGID had a higher risk of
      having a history of some kind of abuse, as compared with the SSF controls (45%
      vs.16%, OR = 2.0, 95% CI: 1.01-3.9; SSF = 1), in contrast to men (29% vs. 24%
      n.s.). Women with a history of abuse and FGID had reduced HRQL 91 (95% CI 85-97)
      as compared with women without abuse history 100 (95% CI 96-104, P = 0.01,
      "healthy" = 102-105 on PGWB). Childhood emotional abuse was a predictor for
      consulting with OR = 4.20 (95% CI: 1.12-15.7.7). Thus, previous abuse is common
      in women with FGID and must be considered by the physician for diagnosis and
      treatment of the disorder.

PMID- 18060498
TI  - 'Real world' comparison of first- and second-generation antipsychotics in regard
      to length of inpatient hospitalization and number of re-hospitalizations.
AB  - The purpose of this study was to determine if Second-Generation Antipsychotics
      (SGAs), relative to First-Generation Antipsychotics (FGAs), reduced either the
      length of stay (LOS) or number of re-hospitalizations of schizophrenic patients
      receiving treatment in a state psychiatric hospital. Medical records were
      compared for the periods 1991-1994 and 2001-2004 for three inpatient groups:
      those receiving FGAs, those receiving SGAs, and those switched from FGAs to SGAs.
      During both time periods, patients on FGAs had significantly shorter LOS than
      either those receiving SGAs or those switched from FGAs to SGAs. Therefore,
      inpatients receiving SGAs were hospitalized longer than those receiving FGAs.
      Conversely, once discharged, patients receiving SGAs were significantly less
      likely to be re-admitted than patients discharged on FGAs. The data suggest that
      some patients do benefit from SGAs and it may be cost-effective in the long-term,
      to determine when to utilize FGAs first and when to switch from the older to the
      newer agents.

PMID- 18060499
TI  - The use of data to assist in the design of a new service system for homeless
      veterans in New York City.
AB  - OBJECTIVE: Operation Home is an agreement between the City of New York and the US
      Department of Veterans Affairs to design a new service system to help end veteran
      homelessness in New York City. The authors' task was to obtain data to inform the
      design of this new system. METHODS: A variety of methods were used. The group
      reviewed relevant literature and data from street homeless survey samples,
      analyzed shelter data, and consulted with VA homeless program staff on the
      findings. We then surveyed case managers at a veterans' shelter regarding their
      clients and determined their housing eligibility using a standardized logic
      model, and led two focus groups of veterans at this shelter regarding their views
      of the current shelter system and services for homeless veterans and how these
      might be improved. RESULTS: Among those resident in shelters during 2006, 37.2%
      of self-identified veterans compared to 0.9% of others reported their prior
      residence as supported housing, suggesting the need for more intensive case
      management at veterans' supported housing sites to help them sustain their
      tenure. The lack of interconnectedness among the various information systems made
      it more difficult to collect and analyze pertinent data. To begin to address
      this, a data match was undertaken to estimate the proportion of veterans resident
      in the veterans' shelter who were not in receipt of VA benefits to which they may
      be entitled. CONCLUSION: The data obtained through collaboration between staff
      from NYC's Department of Homelessness Services, US Department of Veterans Affairs
      facilities in the New York/New Jersey region and Common Ground Community led to
      information that informed the evaluation design of the new system. The
      identification of gaps in available data on homeless veterans will lead to
      projects both to improve and share data.

PMID- 18060501
TI  - The COP9 signalosome-mediated deneddylation is stimulated by caspases during
      apoptosis.
AB  - In concert with the ubiquitin (Ub) proteasome system (UPS) the COP9 signalosome
      (CSN) controls the stability of cellular regulators. The CSN interacts with
      cullin-RING Ub ligases (CRLs) consisting of a specific cullin, a RING protein as
      Rbx1 and substrate recognition proteins. The Ub-like protein Nedd8 is covalently
      linked to cullins and removed by the CSN-mediated deneddylation. Cycles of
      neddylation and deneddylation regulate CRLs. Apoptotic stimuli cause caspase
      dependent modifications of the UPS. However, little is known about the CSN during
      apoptosis. We demonstrate in vitro and in vivo that CSN6 is cleaved most
      effectively by caspase 3 at D23 after 2-3 h of apoptosis induced by anti-Fas-Ab
      or etoposide. CSN6 processing occurs in CSN-CRL complexes and is followed by the
      cleavage of Rbx1, the direct interaction partner of CSN6. Caspase-dependent
      cutting of Rbx1 is accompanied by decrease of neddylated proteins in Jurkat T
      cells. Another functional consequence of CSN6 cleavage is the enhancement of CSN
      mediated deneddylating activity causing deneddylation of cullin 1 in cells. The
      CSN-associated deubiquitinating as well as kinase activity remained unchanged in
      presence of active caspase 3. The cleavage of Rbx1 and increased deneddylation of
      cullins inactivate CRLs and presumably stabilize pro-apoptotic factors for final
      apoptotic steps.

PMID- 18060500
TI  - Health competence as predictor of access to care among Latinos in Baltimore.
AB  - The goal of this study is to identify the underlying structure of Health
      Competence and its value as a predictor of access to care among the Latino
      population in Baltimore, Maryland. Data on a cross-sectional urban probability
      sample were collected from 330 foreign-born Latino men and women aged 21-75 years
      residing in Baltimore at the time of the survey. Principal components analysis
      yielded a two-component solution: the first component comprised "factors
      enabling" access to care; the second, "perceived barriers". When testing the
      predictive power of the Health Competence construct using model building and the
      log likelihood criteria the "enabling factors" added significantly (P < .005) to
      the power of the socio-demographic variables to predict access to care, making it
      an important tool for programs aiming to improve US Latinos' health.

PMID- 18060502
TI  - RNA interference against HPV16 E7 oncogene leads to viral E6 and E7 suppression
      in cervical cancer cells and apoptosis via upregulation of Rb and p53.
AB  - The simultaneous expression of human papillomavirus type 16 (HPV16) E6 and E7
      oncogenes is pivotal for malignant transformation and maintenance of malignant
      phenotypes. Silencing these oncogenes is considered to be applicable in molecular
      therapies of human cervical cancer. However, it remains to be determined whether
      HPV16 E6 and E7 could be both silenced to obtain most efficient antitumor
      activity by using RNA interference (RNAi) technology. Herein, we designed a small
      interfering RNA (siRNA) targeting HPV16-E7 region to degrade either E6, or
      truncated E6 (E6*) and E7 mRNAs and to simultaneously knockdown both E6 and E7
      expression. Firstly, the sequence targeting HPV16-E7 region was inserted into the
      shRNA packing vector pSIREN-DNR, yielding pSIREN-16E7 to stably express
      corresponding shRNA. HPV16-transformed SiHa and CaSki cells were used as a model
      system; RT-PCR, Western Blotting, MTT assay, TUNEL staining, Annexin V apoptosis
      assay and flow cytometry were applied to examine the effects of pSIREN-16E7. Our
      results indicated that HPV16-E7 specific shRNA (16E7-shRNA) induced selective
      degradation of E6 and E7 mRNAs and proteins. E6 silencing induced accumulation of
      cellular p53 and p21. In contrast, E7 silencing induced hypophosphorylation of
      retinoblastoma (Rb) protein. The loss of E6 and E7 reduced cell growth and
      ultimately resulted in massive apoptotic cell death selectively in HPV-positive
      cancer cells, compared with the HPV-negative ones. We demonstrated that 16E7
      shRNA can induce simultaneous E6 and E7 suppression and lead to striking
      apoptosis in HPV16-related cancer cells by activating cellular p53, p21 and Rb.
      Therefore, RNAi using E7 shRNA may have the gene-specific therapy potential for
      HPV16-related cancers.

PMID- 18060503
TI  - The novel phospholipase C activator, m-3M3FBS, induces apoptosis in tumor cells
      through caspase activation, down-regulation of XIAP and intracellular calcium
      signaling.
AB  - We investigated the effect of the novel phospholipase C activator, m-3M3FBS, on
      the apoptosis of human renal Caki cancer cells. Treatment with m-3M3FBS induced
      apoptosis of Caki cells, which was accompanied by accumulation of sub-G1 phase
      and DNA fragmentation. We found that induction of apoptosis is a common response
      of several cancer cell types to m-3M3FBS treatment. Overexpression of Bcl-2 and c
      FLIPs fails to block m-3M3FBS-induced apoptosis. However, ectopic expression of
      XIAP partly inhibits m-3M3FBS-induced apoptosis in Caki cells. m-3M3FBS-induced
      apoptosis appeared to involve the XIAP down-regulation and caspase activation. m
      3M3FBS also induced the expression of a potential proapoptotic gene, C/EBP
      homologous protein (CHOP), however, suppression of CHOP expression by small
      interfering RNA did not abrogate the m-3M3FBS-induced apoptosis. In addition,
      inhibition of phospholipase C (PLC) or chelation of intracellular calcium
      prevented m-3M3FBS-induced apoptosis in Caki cells, suggesting that the
      involvement of PLC pathway and intracellular calcium signaling on the apoptosis
      in m-3M3FBS-treated Caki cells. Collectively, our present results suggest that m
      3M3FBS-induced apoptosis in Caki cells may result from the activation of caspase,
      down-regulation of XIAP and intracellular Ca(2+) release pathway and that m
      3M3FBS treatment might overcome the anti-apoptotic effect of Bcl-2 or c-FLIPs in
      cancer cells.

PMID- 18060504
TI  - Apoptosis-associated antigens recognized by autoantibodies in patients with the
      autoimmune liver disease primary biliary cirrhosis.
AB  - There is growing evidence that the onset of autoimmune disorders can be linked to
      the inefficient removal of apoptotic cells. Since defects in the elimination of
      apoptotic cells lead to secondary necrosis and subsequent release of
      intracellular components, this might explain the generation of autoantibodies
      against intracellular antigens. Accordingly, we wanted to investigate, whether
      antibodies from patients with the autoimmune liver disease primary biliary
      cirrhosis (PBC) recognize self-proteins generated and released during apoptosis.
      Using Western blot analyses we could detect intracellular antigens with serum IgG
      from PBC patients but not with serum IgG from healthy donors in lysates of Jurkat
      T-leukemia, HepG2 hepatoma, and HT-29 colon-carcinoma cells. Interestingly, PBC
      serum IgG also recognized caspase substrates in cells undergoing apoptosis
      induced by staurosporine or TRAIL (TNF-related apoptosis inducing ligand). In
      addition to intracellular antigens, serum IgG from PBC patients detected caspase
      dependent antigens in the supernatants of apoptotic (secondary necrotic) cells
      and antigens on the surface of apoptotic Jurkat cells. Among the caspase
      substrates recognized by PBC serum IgG we could identify the components PDC-E2
      and -E1beta of the known autoantigen PDC (pyruvate dehydrogenase complex). Thus,
      caspase-mediated processing of intracellular proteins might generate de novo
      autoantigens that upon release contribute to the generation of autoantibodies and
      autoimmune diseases as PBC.

PMID- 18060505
TI  - Estimating the domain of applicability for machine learning QSAR models: a study
      on aqueous solubility of drug discovery molecules.
AB  - We investigate the use of different Machine Learning methods to construct models
      for aqueous solubility. Models are based on about 4000 compounds, including an in
      house set of 632 drug discovery molecules of Bayer Schering Pharma. For each
      method, we also consider an appropriate method to obtain error bars, in order to
      estimate the domain of applicability (DOA) for each model. Here, we investigate
      error bars from a Bayesian model (Gaussian Process (GP)), an ensemble based
      approach (Random Forest), and approaches based on the Mahalanobis distance to
      training data (for Support Vector Machine and Ridge Regression models). We
      evaluate all approaches in terms of their prediction accuracy (in cross
      validation, and on an external validation set of 536 molecules) and in how far
      the individual error bars can faithfully represent the actual prediction error.

PMID- 18060506
TI  - An eleven amino acid residue deletion expands the substrate specificity of acetyl
      xylan esterase II (AXE II) from Penicillium purpurogenum.
AB  - The soft-rot fungus Penicillium purpurogenum secretes to the culture medium a
      variety of enzymes related to xylan biodegradation, among them three acetyl xylan
      esterases (AXE I, II and III). AXE II has 207 amino acids; it belongs to family 5
      of the carbohydrate esterases and its structure has been determined by X-ray
      crystallography at 0.9 A resolution (PDB 1G66). The enzyme possesses the
      alpha/beta hydrolase fold and the catalytic triad typical of serine esterases
      (Ser90, His187 and Asp175). AXE II can hydrolyze esters of a large variety of
      alcohols, but it is restricted to short chain fatty acids. An analysis of its
      three-dimensional structure shows that a loop that covers the active site may be
      responsible for this strict specificity. Cutinase, an enzyme that hydrolyzes
      esters of long chain fatty acids and shows a structure similar to AXE II, lacks
      this loop. In order to generate an AXE II with this broader specificity, the
      preparation of a mutant lacking residues involving this loop (Gly104 to Ala114)
      was proposed. A set of molecular simulation experiments based on a comparative
      model of the mutant enzyme predicted a stable structure. Using site-directed
      mutagenesis, the loop's residues have been eliminated from the AXE II cDNA. The
      mutant protein has been expressed in Aspergillus nidulans A722 and Pichia
      pastoris, and it is active towards a range of fatty acid esters of up to at least
      14 carbons. The availability of an esterase with broader specificity may have
      biotechnological applications for the synthesis of sugar esters.

PMID- 18060507
TI  - The impact of genetic parental distance on developmental stability and fitness in
      Drosophila buzzatii.
AB  - Measures of genetic parental distances (GPD) based on microsatellite loci (D(2)
      and IR), have been suggested to be better correlated with fitness than individual
      heterozygosity (H), as they contain information about past events of inbreeding
      or admixture. We investigated if GPD increased with increasing genetic divergence
      between parental populations in Drosophila buzzatii and if the measures indicate
      past events of admixture. Further we evaluated the relationship between GPD,
      fitness and fluctuating asymmetry (FA) of size and shape. We investigated three
      populations of Drosophila buzzati, from Argentina, Europe and Australia. From
      these populations two intraspecific hybridisation lines were made; one between
      the Argentinean and European populations, which have been separated 200 years and
      one between the populations from Argentina and Australia, which have been
      separated 80 years. By doing this we obtained hybrid progeny having different
      levels of GPD. We found that D(2) and H can be used as indicators of admixture
      when comparing hybrid individuals with their parentals. IR was not informative.
      Our results does not exclude the presence of genetic fitness correlations (GFC)
      over individuals with a broad fitness range from populations in equilibrium, but
      we doubt the presence of GFC using GPD measures in admixed populations. Shape FA
      could be a relevant measure for fitness, however, only when comparing
      populations, not at individual level.

PMID- 18060508
TI  - Assessment of power and accuracy of methods for detection and frequency
      estimation of null alleles.
AB  - Null alleles represent a common artefact of microsatellite-based analyses. Rapid
      methods for their detection and frequency estimation have been proposed to
      replace the existing time-consuming laboratory methods. The objective of this
      paper is to assess the power and accuracy of these statistical tools using both
      simulated and real datasets. Our results revealed that none of the tests
      developed to detect null alleles are perfect. However, combining tests allows the
      detection of null alleles with high confidence. Comparison of the estimators of
      null allele frequency indicated that those that account for unamplified
      individuals, such as the Brookfield2 estimator, are more accurate than those that
      do not. Altogether, the use of statistical tools appeared more appropriate than
      testing with alternative primers as null alleles often remain undetected
      following this laborious work. Based on these results, we propose recommendations
      to detect and correct datasets with null alleles.

PMID- 18060509
TI  - N,N-Dialkylaminostyryl dyes: specific and highly fluorescent substrates of
      peroxidase and their application in histochemistry.
AB  - Fluorescent labeling of immuno-bound or endogenous peroxidase (PO) activity has
      been achieved to date by means of phenol derivatives with a low substitution
      degree. Here it is demonstrated that N,N-dialkylamino-styryl dyes can also act as
      fluorescent substrates of PO. They undergo enzymatically cross-linking reactions
      to surrounding cell constituents in an analogous manner thus permitting highly
      fluorescent and permanent labeling. This approach is narrowly related to the
      catalyzed reporter deposition (CARD) technique based on tyramine conjugates and
      the recently described catalytic cross-linking approach of hydroxystyryl
      derivatives. The substitution patterns for optimal cross-linking capability and
      the spectral properties of obtained specific reaction products were studied using
      an iterative semi-empirical approach. The best staining performance is achieved
      with N,N-dimethylaminoaryl derivatives. Their N,N-dialkyl homologues as well as
      the primary aryl amine pendants failed as PO substrates. Due to their basic
      character, novel substrates occasionally tend to unspecific interactions
      (staining nuclei, mast cells, or keratin). Centering this side specificity and
      repressing the staining capability of PO was achieved by chemical modification of
      the respective dye leading to new specific probes for keratin and cytoplasmatic
      RNA. In conclusion, catalytic cross-linking of heterocyclic 4-N,N-dimethylamino
      styryl dyes represents a promising approach for the permanent fluorescent
      staining of PO in fixed cells and tissues, complementing the CARD technique. In
      contrast to CARD-related approaches, new substrates are characterized by a broad
      excitation and emission range of fluorescence and the outstanding spatial
      resolution of specific fluorescence signaling known so far from their 4
      hydroxystyryl analogues. They currently represent the smallest fluorescent
      substrates of PO. Histochemical and immuno-histochemical applications share
      several outstanding features: High detection sensitivity, spatial resolution of
      fluorescence signaling, and photo stability. 4-N,N-dimethylamino-styryl
      substrates are compatible with their phenol and phenol-ester analogues. Their
      combination facilitates the trichromatic immuno-histochemical demonstration of
      three different targets simultaneously at one excitation wavelength in a
      conventional epi-fluorescence microscope.

PMID- 18060510
TI  - Differential gene expression analysis of tubule forming and non-tubule forming
      endothelial cells: CDC42GAP as a counter-regulator in tubule formation.
AB  - The formation of new tubular structures from a quiescent endothelial lining is
      one of the hallmarks of sprouting angiogenesis. This process can be mimicked in
      vitro by inducing capillary-like tubular structures in a three-dimensional (3D)
      fibrin matrix. We aimed to analyze the differential mRNA expression in two
      phenotypically distinct cell populations from the same culture, namely in tubule
      forming endothelial cells and monolayer endothelial cells not participating in
      tubule formation. A fibrin-rich 3D matrix derived from human plasma was used to
      facilitate tubule formation by human foreskin microvascular endothelial cells
      (hMVEC). After 7 days of stimulation with VEGF, bFGF, and TNF-alpha, the culture
      consisted of a monolayer and capillary-like sprouts that had grown into the
      fibrinous matrix. A method was developed to separate the monolayer and tubule
      forming populations of hMVEC, keeping their cellular integrity intact to ensure
      mRNA extraction and cDNA production. Subsequent array analysis resulted in an
      inventory of differentially expressed genes that were associated with either tube
      forming (angiogenic) or non-angiogenic capacity. Differential gene expression was
      verified by real-time PCR on the original RNA samples as well as on RNA obtained
      from laser-capture microdissected cross sections of monolayers and capillary
      structures in the 3D fibrinous matrix. The expression of CDC42GAP, an inhibitor
      of active-state small Rho GTPases, was reduced in tubular hMVEC. Overexpression
      of CDC42GAP in hMVEC attenuated endothelial tubule formation, while its
      suppression by siRNA slightly enhanced this process. Thus, CDC42GAP was
      identified as a counter-regulatory mediator for tubule formation.

PMID- 18060512
TI  - Determination of O(3), NO (2), SO (2), CO and PM (10) measured in Belgrade urban
      area.
AB  - O(3), NO(2), SO(2), CO and PM(10) concentrations, simultaneously determined for
      the first time in Belgrade urban area in the autumnal period of 2005, are
      presented. The obtained results display similar behaviour of SO(2), NO(2), CO,
      PM(10) opposite from that of O(3). The weekend effect was also investigated
      showing diminution of average daily concentrations of SO(2), NO(2), PM(10) and CO
      for 72, 40, 37 and 42% respectively, and increase of the average daily
      concentration of O(3) for 56%. Influence of meteorological conditions on observed
      concentration levels was studied, too. The observed influence of wind speed on
      the O(3) nightly concentration levels was analyzed pointing to the phenomena of
      O(3) transport during episodic measurements. To make an identification of
      possible pollution sources and analyse the influence of meteorological parameters
      on pollution levels, air back trajectories for high level concentrations episodes
      were calculated and analysed. A multivariate receptor modelling (Principal
      Component Analysis, Cluster Analysis) has been applied to a set of data in order
      to determine the contribution of different sources. It was found that the main
      principal components, extracted from the air pollution data, were related to
      gasoline combustion, oil combustion and ozone transport.

PMID- 18060513
TI  - Hydrology, suspended sediment dynamics and nutrient loading in Lake Takkobu, a
      degrading lake ecosystem in Kushiro Mire, northern Japan.
AB  - Suspended sediment and nutrient loadings from agricultural watersheds have lead
      to habitat degradation in Lake Takkobu. To examine their relationships with land
      use activities, we monitored sediment, nutrient and water discharges into the
      lake for a 1-year sampling period. The Takkobu River contributed the largest
      portion of the annual water discharge into the lake, compared with the other
      tributaries. During dry conditions, lake water flowed into the Kushiro River, and
      conversely during flooding, Kushiro River water flowed into the lake. Inflows
      from the Kushiro River had a high proportion of inorganic matter, with high
      concentrations of total nitrogen and total phosphorus, attributed to agricultural
      land-use development and stream channelization practiced since the 1960s in the
      Kushiro Mire. Nutrient loadings from these two rivers were significantly higher
      during flooding than in dry conditions. However, there was no clear correlation
      between river discharge and nutrient concentrations. Since land-use activities in
      the Kushiro River and Takkobu River watersheds were concentrated near rivers,
      nutrients easily entered the drainage system under low flow conditions. In
      contrast, water discharged from small, forest-dominated watersheds contained a
      low proportion of inorganic matter, and low nutrient concentrations. The
      suspended sediment delivered to the lake during the sample period was estimated
      as approximately 607 tons, while the total nitrogen and total phosphorus inflows
      were about 10,466 and 1,433 kg, respectively. Suspended sediment input into the
      lake was 65%, and total nitrogen and total phosphorus were 40% and 48%,
      respectively, being delivered by the Kushiro River.

PMID- 18060514
TI  - Vitamin D receptor levels and binding are reduced in aged rat intestinal
      subcellular fractions.
AB  - The hormonal form of vitamin D, 1alpha,25(OH)(2)-vitaminD(3)
      [1alpha,25(OH)(2)D(3)], stimulates signal transduction pathways in intestinal
      cells. To gain insight into the relative importance of the vitamin D receptor
      (VDR) in the rapid hormone responses, the amounts and localization of the VDR
      were evaluated in young (3 months) and aged (24 months) rat intestinal cells.
      Immune-fluorescence and Western blot studies showed that VDR levels are
      diminished in aged enterocytes. Confocal microscopy assays revealed that the VDR
      and other immune-reactive proteins have mitochondrial, membrane, cytosol and
      perinuclear localization. Western blot analysis using specific antibodies
      detected the 60 and 50 kDa bands expected for the VDR in the cytosol and
      microsomes and, to a lesser extent, in the nucleus and mitochondria. Low
      molecular weight immune-reactive proteins were also detected in young enterocytes
      subcellular fractions. Since changes in hormone receptor levels appear to
      constitute a common manifestation of the ageing process, we also analyzed
      1alpha,25(OH)(2)D(3) binding properties and VDR levels in subcellular fractions
      from young and aged rats. In competition binding assays, employing [(3)H]
      1alpha,25(OH)(2)D(3) and 1alpha,25(OH)(2)D(3), we have detected specific binding
      in all subcellular fractions, with maximum binding in mitochondrial and nuclear
      fractions. Both, VDR protein levels and 1alpha,25(OH)(2)D(3) binding, were
      diminished with ageing. Age-related declines in VDR may have important
      consequences for correct receptor/effector coupling in the duodenal tissues and
      may explain age-related declines in the hormonal regulation of signal
      transduction pathways that we previously reported.

PMID- 18060515
TI  - Energy metabolism in Desulfovibrio vulgaris Hildenborough: insights from
      transcriptome analysis.
AB  - Sulphate-reducing bacteria are important players in the global sulphur and carbon
      cycles, with considerable economical and ecological impact. However, the process
      of sulphate respiration is still incompletely understood. Several mechanisms of
      energy conservation have been proposed, but it is unclear how the different
      strategies contribute to the overall process. In order to obtain a deeper insight
      into the energy metabolism of sulphate-reducers whole-genome microarrays were
      used to compare the transcriptional response of Desulfovibrio vulgaris
      Hildenborough grown with hydrogen/sulphate, pyruvate/sulphate, pyruvate with
      limiting sulphate, and lactate/thiosulphate, relative to growth in
      lactate/sulphate. Growth with hydrogen/sulphate showed the largest number of
      differentially expressed genes and the largest changes in transcript levels. In
      this condition the most up-regulated energy metabolism genes were those coding
      for the periplasmic [NiFeSe] hydrogenase, followed by the Ech hydrogenase. The
      results also provide evidence for the involvement of formate cycling and the
      recently proposed ethanol pathway during growth in hydrogen. The pathway
      involving CO cycling is relevant during growth on lactate and pyruvate, but not
      during growth in hydrogen as the most down-regulated genes were those coding for
      the CO-induced hydrogenase. Growth on lactate/thiosulphate reveals a down
      regulation of several energy metabolism genes similar to what was observed in the
      presence of nitrite. This study identifies the role of several proteins involved
      in the energy metabolism of D. vulgaris and highlights several novel genes
      related to this process, revealing a more complex bioenergetic metabolism than
      previously considered.

PMID- 18060516
TI  - Galleria mellonella and the study of fungal pathogenesis: making the case for
      another genetically tractable model host.

PMID- 18060517
TI  - Identification and characterization of cyclin X which activates transcriptional
      activities of c-Myc.
AB  - Cyclins are eukaryotic proteins that play an active role in controlling cell
      division cycles and regulate cyclin dependent kinases (CDKs). In this study, we
      identified and characterized a new member of the human cyclin family. Its cDNA
      sequence contains an open reading frame of 864 bp, encoding a protein of 287
      amino acids. This putative cyclin, designated cyclin X, contains a typical cyclin
      box. Cyclin X shows the highest sequence similarity in cyclin box to cyclin B3
      and the similarity between these two proteins also extends to the whole molecule.
      The expression pattern of cyclin X showed that it was highly expressed in testis.
      Cyclin X protein was located in nucleus of the H1299 cells and Overexpression of
      cyclin X activated the transcriptional activities of c-Myc. These results
      indicate that cyclin X is a novel member of the human cyclin family and positive
      regulator of c-Myc-mediated gene transcription.

PMID- 18060518
TI  - Ethical and philosophical consideration of the dual-use dilemma in the biological
      sciences.
AB  - The dual-use dilemma arises in the context of research in the biological and
      other sciences as a consequence of the fact that one and the same piece of
      scientific research sometimes has the potential to be used for bad as well as
      good purposes. It is an ethical dilemma since it is about promoting good in the
      context of the potential for also causing harm, e.g., the promotion of health in
      the context of providing the wherewithal for the killing of innocents. It is an
      ethical dilemma for the researcher because of the potential actions of others,
      e.g., malevolent non-researchers who might steal dangerous biological agents, or
      make use of the original researcher's work. And it is a dilemma for governments
      concerned with the security of their citizens, as well as their health. In this
      article we construct a taxonomy of types of "experiments of concern" in the
      biological sciences, and thereby map the terrain of ethical risk. We then provide
      a series of analyses of the ethical problems and considerations at issue in the
      dual-use dilemma, including the impermissibility of certain kinds of research and
      possible restrictions on dissemination of research results given the risks to
      health and security. Finally, we explore the main available institutional
      responses to some of the specific ethical problems posed by the dual-use dilemma
      in the biological sciences.

PMID- 18060524
TI  - Biological and chemical characterization of metal bioavailability in sediments
      from Lake Roosevelt, Columbia River, Washington, USA.
AB  - We studied the bioavailability and toxicity of copper, zinc, arsenic, cadmium,
      and lead in sediments from Lake Roosevelt (LR), a reservoir on the Columbia River
      in Washington, USA that receives inputs of metals from an upstream smelter
      facility. We characterized chronic sediment toxicity, metal bioaccumulation, and
      metal concentrations in sediment and pore water from eight study sites: one site
      upstream in the Columbia River, six sites in the reservoir, and a reference site
      in an uncontaminated tributary. Total recoverable metal concentrations in LR
      sediments generally decreased from upstream to downstream in the study area, but
      sediments from two sites in the reservoir had metal concentrations much lower
      than adjacent reservoir sites and similar to the reference site, apparently due
      to erosion of uncontaminated bank soils. Concentrations of acid-volatile sulfide
      in LR sediments were too low to provide strong controls on metal bioavailability,
      and selective sediment extractions indicated that metals in most LR sediments
      were primarily associated with iron and manganese oxides. Oligochaetes
      (Lumbriculus variegatus) accumulated greatest concentrations of copper from the
      river sediment, and greatest concentrations of arsenic, cadmium, and lead from
      reservoir sediments. Chronic toxic effects on amphipods (Hyalella azteca; reduced
      survival) and midge larvae (Chironomus dilutus; reduced growth) in whole-sediment
      exposures were generally consistent with predictions of metal toxicity based on
      empirical and equilibrium partitioning-based sediment quality guidelines.
      Elevated metal concentrations in pore waters of some LR sediments suggested that
      metals released from iron and manganese oxides under anoxic conditions
      contributed to metal bioaccumulation and toxicity. Results of both chemical and
      biological assays indicate that metals in sediments from both riverine and
      reservoir habitats of Lake Roosevelt are available to benthic invertebrates.
      These findings will be used as part of an ongoing ecological risk assessment to
      determine remedial actions for contaminated sediments in Lake Roosevelt.

PMID- 18060523
TI  - Mental health of recently resettled refugees from the Middle East in Sweden: the
      impact of pre-resettlement trauma, resettlement stress and capacity to handle
      stress.
AB  - The pathways to symptoms of common mental disorder and post-traumatic stress
      symptoms among refugees during resettlement need to be better specified. We aim
      to identify models of these different mental health outcomes among refugees
      during resettlement, taking pre-migration, migration and post-migration stress
      conditions, a person's capacity to handle such stress and socio-demographic
      variables into consideration. A new questionnaire developed to better cover
      resettlement stress, as well as pre-resettlement trauma exposures and different
      measures of a person's capacity to handle stress, was administered to 124 Middle
      Eastern refugees that had been granted permanent residency in Sweden only a few
      months before responding. We found four dimensions of resettlement stress: social
      and economic strain, alienation, discrimination and status loss and violence and
      threats in Sweden, that account for 62% of the total variance in resettlement
      stress. Social and economic strain and alienation are important for explaining
      symptoms of common mental disorder. In the model of core post-traumatic stress
      symptoms, pre-resettlement trauma exposure seems to have the strongest impact. A
      person's capacity to handle stress plays significant, direct and mediating roles
      in both models. The impact of resettlement stressors in the context of the whole
      migration process for different mental health outcomes is discussed.

PMID- 18060525
TI  - Automated multidetector row CT dataset segmentation with an interactive watershed
      transform (IWT) algorithm: Part 1. Understanding the IWT technique.
AB  - Segmentation of volumetric computed tomography (CT) datasets facilitates
      evaluation of 3D CT angiography renderings, particularly with maximum intensity
      projection displays. This manuscript describes a novel automated bone editing
      program that uses an interactive watershed transform (IWT) technique to rapidly
      extract the skeletal structures from the volume. Advantages of this tool include
      efficient segmentation of large datasets with minimal need for correction. In the
      first of this two-part series, the principles of the IWT technique are reviewed,
      followed by a discussion of clinical utility based on our experience.

PMID- 18060526
TI  - Taurine inhibits osteoblastic differentiation of vascular smooth muscle cells via
      the ERK pathway.
AB  - Vascular calcification develops within atherosclerotic lesions and results from a
      process similar to osteogenesis. Taurine is a free beta-amino acid and plays an
      important physiological role in mammals. We have recently demonstrated that
      vascular smooth muscle cells (VSMCs) express a functional taurine transporter. To
      evaluate the possible role of taurine in vascular calcification, we assessed its
      effects on osteoblastic differentiation of VSMCs in vitro. The results showed
      that taurine inhibited the beta-glycerophosphate-induced osteoblastic
      differentiation of VSMCs as evidenced by both the decreasing alkaline phosphate
      (ALP) activity and expression of the core binding factor alpha1 (Cbfalpha1).
      Taurine also activated the extracellular signal-regulated protein kinase (ERK)
      pathway. Inhibition of ERK pathway reversed the effect of taurine on ALP activity
      and Cbfalpha1 expression. These results suggested that taurine inhibited
      osteoblastic differentiation of vascular cells via the ERK pathway.

PMID- 18060527
TI  - Glutamine enhances glucose-induced mesangial cell proliferation.
AB  - The proliferation of mesangial cells (MC) in the presence of glutamine (0-20 mM)
      was determined in both low (5 mM) and high (25 mM) glucose-containing medium.
      Glutamine in a high glucose (HG) environment increased cell proliferation in a
      dose-dependent manner. Inhibition of glutamine:fructose 6-phosphate
      amidotransferase (GFAT) and of phosphodiesterase significantly reduced glutamine
      induced proliferation. Supraphysiologic levels of glutamine increase MC
      proliferation in a HG milieu via GFAT and cAMP-dependent pathways, suggesting
      that glutamine could pose a risk for diabetic nephropathy.

PMID- 18060528
TI  - Endoscopic lesions in low-to average-risk patients with minimal bright red
      bleeding from midline anal fissures. How much should we go in?
AB  - BACKGROUND: Anal fissure is a common condition in young patients, and the main
      symptoms include anal pain and bleeding. Our aim was to determine the need to
      perform lower gastrointestinal endoscopy on patients with midline anal fissure
      who present with minimal bright red rectal bleeding and who are at low risk for
      colorectal neoplasia. METHODS: Patients with midline anal fissure who reported
      small amounts of red blood on toilet paper, toilet bowl or stool after defecation
      were evaluated. Patients with alarm signs (recently altered bowel habit, weight
      loss, anemia and family or personal history of colorectal neoplasms) were
      excluded. A total of 134 patients (80 female and 54 male, aged 35.8+/-11.4 years)
      were studied. Patients younger than 40 years underwent flexible sigmoidoscopy and
      colonoscopy was used for older ones. RESULTS: Fissures were posterior in 106
      cases (79.1%) and anterior in 27 cases (20.1%); one patient (0.7%) had both
      anterior and posterior fissures. The lower gastrointestinal endoscopy was normal
      in 120 patients (89.6%), and 36 patients (26.9%) had associated internal
      hemorrhoids. Adenomatous polyps were found in 4 cases (3.0%), ulcerative colitis
      in 8 (6.0%) and Crohn's disease in one patient (0.7%). There was no case of
      adenocarcinoma. CONCLUSIONS: Clinical evaluation plus rectoscopy might be the
      appropriate evaluation in this selected group of patients, if our results are
      confirmed by further studies.

PMID- 18060530
TI  - Anal dilatation versus left lateral sphincterotomy for chronic anal fissure: a
      prospective randomized study.
AB  - BACKGROUND: Several surgical methods are accepted for the treatment of chronic
      anal fissure. The most popular are anal dilatation (AD) and left lateral
      sphincterotomy (LLS). The objective of the current study was to prospectively
      evaluate the results of these two procedures in terms of recurrence rate,
      complications and patient satisfaction. METHODS: The study enrolled all patients
      who required operation for chronic anal fissure in the Division of General
      Surgery, Campus Golda, Rabin Medical Center, between the years 1997 and 2001.
      Exclusion criteria were acute anal fissure or inflammatory bowel disease.
      RESULTS: A total of 108 patients participated in the study, at an average age of
      42.4 years (SD=12.5). The patients were randomly assigned to two groups; one for
      LLS (53 patients, 49.1%) and one for AD (55 patients, 50.9%). The study protocol
      included a questionnaire and a physical examination performed 1, 2, 3, 6 and 12
      months after operation. The questionnaire contained questions about pain, bloody
      stool, incontinence for gas, fluid or hard feces, during the day or night, and
      soiling. The patients were also asked about their satisfaction on an analog scale
      from 1 to 10. The average follow-up was 11.2 months (SD=4.1). Minor incontinence
      occurred in 8 patients of AD group and in 2 patients of LLS group (p<0.005).
      Recurrence occurred in 6 cases of the AD group and in one case of the LLS group
      (p<0.003). Satisfaction score was insignificantly higher in the LLS group (9.1+/
      0.8 in the LLS group and 7.4+/-2.0 in the AD group). CONCLUSIONS: These results
      suggest that LLS is the preferred method for the treatment for chronic anal
      fissure.

PMID- 18060529
TI  - Transanal haemorrhoidal dearterialisation: nonexcisional surgery for the
      treatment of haemorrhoidal disease.
AB  - BACKGROUND: Transanal haemorrhoidal dearterialisation (THD) is a nonexcisional
      surgical technique for the treatment of piles, consisting in the ligation of the
      distal branches of the superior rectal artery, resulting in a reduction of blood
      flow and decongestion of the haemorrhoidal plexus. The aim of this study was to
      assess the long-term efficacy of this treatment. METHODS: The procedure was
      carried out using a proctoscope with a Doppler probe. The terminal branches were
      located with Doppler and then sutured. RESULTS: From January 2000 to May 2006, we
      performed THD in 330 patients (180 men; mean age, 52.4 years), including 138
      second-degree, 162 third-degree and 30 fourth-degree haemorrhoids. There were 23
      postoperative complications (7 cases of bleeding, 5 thrombosed piles, 4 rectal
      haematomas, 2 anal fissures, 2 cases of dysuria, 1 of haematuria and 2 needle
      ruptures). The mean postoperative pain score was 1.32 on a visual analog scale.
      219 patients were followed for a mean of 46 months (range, 22-79), including 100
      patients with second-degree, 104 with third-degree and 15 with fourth-degree
      haemorrhoids. The operation completely resolved the symptoms in 132 patients
      (92.5%) with preoperative bleeding and in 110 patients (92%) with preoperative
      prolapse. CONCLUSIONS: The efficacy and relapse rate of this procedure appears to
      be similar to that of traditional surgery and stapled haemorrhoidopexy. The
      technique was effective and safe for all degrees of haemorrhoids because of the
      excellent results, low complication rate and minor postoperative pain.

PMID- 18060532
TI  - Three-dimensional quantitative structure-activity relationship (3D QSAR) and
      pharmacophore elucidation of tetrahydropyran derivatives as serotonin and
      norepinephrine transporter inhibitors.
AB  - Three-dimensional quantitative structure-activity relationship (3D QSAR) using
      comparative molecular field analysis (CoMFA) was performed on a series of
      substituted tetrahydropyran (THP) derivatives possessing serotonin (SERT) and
      norepinephrine (NET) transporter inhibitory activities. The study aimed to
      rationalize the potency of these inhibitors for SERT and NET as well as the
      observed selectivity differences for NET over SERT. The dataset consisted of 29
      molecules, of which 23 molecules were used as the training set for deriving CoMFA
      models for SERT and NET uptake inhibitory activities. Superimpositions were
      performed using atom-based fitting and 3-point pharmacophore-based alignment. Two
      charge calculation methods, Gasteiger-Huckel and semiempirical PM3, were tried.
      Both alignment methods were analyzed in terms of their predictive abilities and
      produced comparable results with high internal and external predictivities. The
      models obtained using the 3-point pharmacophore-based alignment outperformed the
      models with atom-based fitting in terms of relevant statistics and
      interpretability of the generated contour maps. Steric fields dominated
      electrostatic fields in terms of contribution. The selectivity analysis (NET over
      SERT), though yielded models with good internal predictivity, showed very poor
      external test set predictions. The analysis was repeated with 24 molecules after
      systematically excluding so-called outliers (5 out of 29) from the model
      derivation process. The resulting CoMFA model using the atom-based fitting
      exhibited good statistics and was able to explain most of the selectivity (NET
      over SERT)-discriminating factors. The presence of -OH substituent on the THP
      ring was found to be one of the most important factors governing the NET
      selectivity over SERT. Thus, a 4-point NET-selective pharmacophore, after
      introducing this newly found H-bond donor/acceptor feature in addition to the
      initial 3-point pharmacophore, was proposed.

PMID- 18060531
TI  - Colorectal stenting as an effective therapy for preoperative and palliative
      treatment of large bowel obstruction: 9 years' experience.
AB  - BACKGROUND: Since their introduction, selfextending metal stents (SEMS) have
      established themselves as an option in the treatment of obstructive colorectal
      cancer. Thanks to stenting, patients traditionally treated with emergency surgery
      can now be converted to scheduled surgery with mechanical preparation of the
      colon and primary anastomosis. Stenting represents a valid one-step surgical
      alternative for intestinal obstruction of the colon. METHODS: We performed a
      prospective study of 95 patients (mean age, 68 years; range 48-94) with large
      bowel obstruction due to colorectal cancer treated with SEMS placed under
      fluoroscopic guidance, some as a bridge to surgery (group A) and others with
      palliative intent (group B). Computed tomography was performed for diagnostic
      purposes and to study the extent of disease. RESULTS: Treatment was palliative in
      28 cases (group B) and as a bridge to surgery in 67 (group A). The latter group
      underwent mechanical preparation of the colon and elective surgery. No patients
      died as a result of the procedure. In 90 cases (95%), treatment was effective and
      the obstruction resolved. Complications were 4 cases of perforation, 1 of
      tenesmus, 4 obstructions and 4 migrations. In 7 cases, a second stent was
      inserted to allow subsequent scheduled surgery. CONCLUSIONS: Self-extending
      stents resolve colorectal cancer obstruction and allow optimal patient staging
      and scheduled surgical treatment. Stenting is also a useful option in advanced or
      irresectable tumors, avoiding the need for surgery and offering good palliation.

PMID- 18060533
TI  - Modulation of intracellular proline levels affects flowering time and
      inflorescence architecture in Arabidopsis.
AB  - We reported previously that the plant oncogene rolD anticipates and stimulates
      flowering in Nicotiana tabacum, and encodes ornithine cyclodeaminase, an enzyme
      catalysing the conversion of ornithine to proline. To investigate on the possible
      role of proline in flowering, we altered the expression of AtP5CS1, encoding the
      rate-limiting enzyme of proline biosynthesis in plants. Accordingly we
      characterized a mutant line containing a T-DNA insertion into AtP5CS1 and
      introduced in Arabidopsis thaliana AtP5CS1 under the control of the CaMV35S
      promoter. As expected homozygous p5cs1 mutants behaved as late flowering. In
      addition p5cs1 mutants exhibited a shorter size and contained lower levels of
      proline, compared to wild type. 35S-P5CS1 plants, manifested, early in
      development, overexpression of P5CS1 and accumulation of proline, leading to
      early flowering, both under long- and short-day conditions. Later in development,
      down-regulation of P5CS1 occurred in 35S-P5CS1 leaves, leading to proline
      reduction, and, in turn, impaired bolting and stunted growth. Salt-stress
      restored expression of P5CS1 and proline accumulation in P5CS1-transformed
      plants, as well as rescuing growth. Our data suggest that proline plays a key
      role in flower transition, bolting and coflorescence formation.

PMID- 18060534
TI  - Assessment of hypercoagulability markers and lipid levels in postmenopausal women
      undergoing either oral or transdermal hormone replacement therapy.
AB  - BACKGROUND: This study investigated the effect of either oral or transdermal
      hormone replacement therapy (HRT) on haemostatic, fibrinolytic and lipid profiles
      in a group of Brazilian women 3 months after beginning treatment by comparing
      these results with those obtained immediately before HRT. METHODS: Plasma levels
      of TAT, DDi, F1+2, PC, PS, AT, PAI-1 and serum lipids were determined in blood
      samples collected from 24 women undergoing oral HRT and from 11 women undergoing
      transdermal HRT. RESULTS: Significant increases in DDi and F1+2 plasma levels
      were observed after 3 months of oral HRT, while PS levels decreased. After
      transdermal HRT, a significant decrease was observed only for AT levels.
      CONCLUSION: After 3 months of oral HRT and in the absence of major genetic and
      acquired risk factors, women displayed a predisposition for activation of blood
      coagulation, and an increased activity of the fibrinolytic system. Oral HRT
      seemed to be more effective in predisposing haemostatic changes as compared to
      transdermal.

PMID- 18060537
TI  - Anticoagulation for mechanical heart valves: a role for patient based therapy.
AB  - Anticoagulation management issues following mechanical cardiac valve replacement
      revolve around target levels for chronic oral anticoagulation. While these levels
      are important, they are only one aspect of a follow-up process that should be
      individualized to each patient with a mechanical cardiac valve and coupled with
      patient education, risk factor modification, and long-term follow-up. It is
      difficult to separate patient related risk factors, those traditional risk
      factors that markedly increase the incidence of potential valve related events
      (i.e., atrial fibrillation), and yet other more subtle non-traditional risk
      factors for thromboembolism (i.e., smoking and hypertension) that contribute to
      events. These also require management during the post-operative period and long
      term follow-up. There are also different risk factors for anatomic valve
      position. The aortic valve is the safest of all the anatomic positions regarding
      valve related events. The mitral valve is at higher risk and the tricuspid valve
      is the most risky anatomic position. Anticoagulation related hemorrhage is the
      most dangerous event for mortality and morbidity in the aortic position,
      thromboembolism in the mitral position, and valve thrombosis in the tricuspid
      position. Each of these requires different degrees of patient modification and
      target levels for anticoagulation. Additionally, low risk patients with aortic
      valve replacement may not require anticoagulant therapy at all. Rather, treatment
      with modern, highly potent platelet inhibiting drugs may be effective after a
      period of sewing ring endothelialization under the protection of antithrombotic
      therapy. Each of these aspects and risk factors is discussed, as well as the call
      for prospective randomized trials treating low risk patients with anti-platelet
      drugs versus warfarin anticoagulation.

PMID- 18060538
TI  - Contributions of microorganisms to industrial biology.
AB  - Life on earth is not possible without microorganisms. Microbes have contributed
      to industrial science for over 100 years. They have given us diversity in
      enzymatic content and metabolic pathways. The advent of recombinant DNA brought
      many changes to industrial microbiology. New expression systems have been
      developed, biosynthetic pathways have been modified by metabolic engineering to
      give new metabolites, and directed evolution has provided enzymes with modified
      selectability, improved catalytic activity and stability. More and more genomes
      of industrial microorganisms are being sequenced giving valuable information
      about the genetic and enzymatic makeup of these valuable forms of life. Major
      tools such as functional genomics, proteomics, and metabolomics are being
      exploited for the discovery of new valuable small molecules for medicine and
      enzymes for catalysis.

PMID- 18060539
TI  - The genetic diversity of UK, US and Australian cultivars of Triticum aestivum
      measured by DArT markers and considered by genome.
AB  - The genetic diversity of UK, US and Australian wheat varieties over the period of
      modern plant breeding is estimated using diversity array technology markers.
      Diversity is assessed by both genetic distance between varieties, by AMOVA and as
      the volumes of multi-dimensional convex hulls estimated from principal co
      ordinate analysis. At the whole genome level the three populations are
      genetically distinct; this is also true of the B genome. However, the US and
      Australian D genomes are found to occupy the same region of diversity space and
      the A genomes for these countries are partially overlapping. The use of high
      density genotyping with a common marker set allows an unprecedented direct
      comparison between the diversities of the national populations, between
      individual genomes and the fluctuation of diversity over time. The highest
      genetic diversity amongst varieties is reported in the Australian population
      followed by the US, which in turn is more diverse than the UK. However the
      average diversity of loci is higher in the US set than in the Australian. Non
      random fluctuations in genetic diversity over time are observed.

PMID- 18060540
TI  - Resistance to Colletotrichum lindemuthianum in Phaseolus vulgaris: a case study
      for mapping two independent genes.
AB  - Anthracnose, caused by the hemibiotrophic fungal pathogen Colletotrichum
      lindemuthianum is a devastating disease of common bean. Resistant cultivars are
      economical means for defense against this pathogen. In the present study, we
      mapped resistance specificities against 7 C. lindemuthianum strains of various
      geographical origins revealing differential reactions on BAT93 and JaloEEP558,
      two parents of a recombinant inbred lines (RILs) population, of Meso-american and
      Andean origin, respectively. Six strains revealed the segregation of two
      independent resistance genes. A specific numerical code calculating the LOD score
      in the case of two independent segregating genes (i.e. genes with duplicate
      effects) in a RILs population was developed in order to provide a recombination
      value (r) between each of the two resistance genes and the tested marker. We
      mapped two closely linked Andean resistance genes (Co-x, Co-w) at the end of
      linkage group (LG) B1 and mapped one Meso-american resistance genes (Co-u) at the
      end of LG B2. We also confirmed the complexity of the previously identified B4
      resistance gene cluster, because four of the seven tested strains revealed a
      resistance specificity near Co-y from JaloEEP558 and two strains identified a
      resistance specificity near Co-9 from BAT93. Resistance genes found within the
      same cluster confer resistance to different strains of a single pathogen such as
      the two anthracnose specificities Co-x and Co-w clustered at the end of LG B1.
      Clustering of resistance specificities to multiple pathogens such as fungi (Co-u)
      and viruses (I) was also observed at the end of LG B2.

PMID- 18060541
TI  - Sepsis mortality prediction based on predisposition, infection and response.
AB  - OBJECTIVE: To empirically test, based on a large multicenter, multinational
      database, whether a modified PIRO (predisposition, insult, response, and organ
      dysfunction) concept could be applied to predict mortality in patients with
      infection and sepsis. DESIGN: Substudy of a multicenter multinational cohort
      study (SAPS 3). PATIENTS: A total of 2,628 patients with signs of infection or
      sepsis who stayed in the ICU for >48 h. Three boxes of variables were defined,
      according to the PIRO concept. Box 1 (Predisposition) contained information about
      the patient's condition before ICU admission. Box 2 (Injury) contained
      information about the infection at ICU admission. Box 3 (Response) was defined as
      the response to the infection, expressed as a Sequential Organ Failure Assessment
      score after 48 h. INTERVENTIONS: None. MAIN MEASUREMENTS AND RESULTS: Most of the
      infections were community acquired (59.6%); 32.5% were hospital acquired. The
      median age of the patients was 65 (50-75) years, and 41.1% were female. About 22%
      (n=576) of the patients presented with infection only, 36.3% (n=953) with signs
      of sepsis, 23.6% (n=619) with severe sepsis, and 18.3% (n=480) with septic shock.
      Hospital mortality was 40.6% overall, greater in those with septic shock (52.5%)
      than in those with infection (34.7%). Several factors related to predisposition,
      infection and response were associated with hospital mortality. CONCLUSION: The
      proposed three-level system, by using objectively defined criteria for risk of
      mortality in sepsis, could be used by physicians to stratify patients at ICU
      admission or shortly thereafter, contributing to a better selection of management
      according to the risk of death.

PMID- 18060542
TI  - The effects of sedation on gastric emptying and intra-gastric meal distribution
      in critical illness.
AB  - OBJECTIVE: To evaluate the effects of sedation with morphine and midazolam (M&M)
      versus propofol on gastric emptying in critically ill patients. DESIGN:
      Descriptive study. SETTING: Mixed medical and surgical intensive care unit.
      PATIENTS: Thirty-six unselected, mechanically ventilated, critically ill
      patients. INTERVENTIONS: Gastric scintigraphic data were analysed retrospectively
      according to whether patients were receiving M&M (n=20; 14M, 6F) or propofol
      (n=16; 7M, 9F). Measurements were performed over 4 h after administration of 100
      ml of Ensure, labelled with 20 MBq Tc99m. MEASUREMENTS AND RESULTS: Gastric half
      emptying time (t1/2) and total and regional (proximal and distal stomach) meal
      retention (%) were assessed. The median t1/2 of patients receiving M&M (153 (IQR:
      72-434) min) was significantly longer than that of patients receiving propofol
      (58 (34-166) min, p=0.02). Total gastric retention was greater in patients
      receiving M&M compared to those receiving propofol (p<0.01). Proximal (p=0.02)
      but not distal (p=0.80) gastric retention was greater in patients who received
      M&M. Patients who received M&M were more likely to have >or=5% meal retention at
      240 min than those treated with propofol (95% (19/20) vs. 56% (9/16); p=0.01).
      Changes in blood glucose concentrations during the study were similar in the two
      groups. CONCLUSIONS: In critical illness, patients receiving M&M for sedation are
      more likely to have slow gastric emptying, and proximal meal retention than those
      receiving propofol. The apparent beneficial effects of propofol-based sedation
      need confirmation by a prospective randomised controlled study.

PMID- 18060544
TI  - Anticipatory postural adjustment: the role of motor cortex in the natural and
      learned bimanual unloading.
AB  - Anticipatory postural adjustment (APA) during bimanual action is observed when
      participants hold an object in one hand and then lift that object with the other
      hand. The decrease in activity of a forearm flexor muscle prior to an active
      forearm unloading acts to stabilize the forearm position. Recent studies have
      investigated the influence of the corticospinal system on muscle activity during
      APA through transcranial magnetic stimulation. It was shown that at different
      times during APA, the amplitude of motor-evoked potentials in the forearm flexors
      decreased in conjunction with the decrease of muscle activity. If the unloading
      is triggered via an electromagnet by lifting an equal weight by the other arm,
      the anticipatory postural adjustment is learned through the repetition of
      unloading (three series of 20 trials). Using the transcranial magnetic
      stimulation, we examined changes in the motor-evoked potential in the forearm
      flexors before and after APA learning. Motor-evoked potential amplitude did not
      significantly change as forearm flexor activity decreased. The motor-evoked
      potential/background electromyogram ratio, however, increased in the final
      learning session in comparison to the initial learning session and stationary
      loading. The present results corroborate a hypothesis on the fundamental role of
      the motor cortex in the suppression of synergies that interfere with the
      execution of the new coordination in the process of motor learning.

PMID- 18060545
TI  - The coordination of eye, head, and arm movements during rapid gaze orienting and
      arm pointing.
AB  - This study aimed to investigate the coordination of multiple control actions
      involved in human horizontal gaze orienting or arm pointing to a common visual
      target. The subjects performed a visually triggered reaction time task in three
      conditions: (1) gaze orienting with a combined eye saccade and head rotation
      (EH), (2) arm pointing with gaze orienting by an eye saccade without head
      rotation (EA), and (3) arm pointing with gaze orienting by a combined eye saccade
      and head rotation (EHA). The subjects initiated eye movement first with nearly
      constant latencies across all tasks, followed by head movement in the EH task, by
      arm movement in the EA task, and by head and then arm movements in the EHA task.
      The differences of onset times between eye and head movements in the EH task, and
      between eye and arm movements in the EA task, were both preserved in the EHA
      task, leading to an eye-to-head-to-arm sequence. The onset latencies of eye and
      head in the EH task, eye and arm in the EA task, and eye, head and arm in the EHA
      task, were all positively correlated on a trial-by-trial basis. In the EHA task,
      however, the correlation coefficients of eye-head coupling and of eye-arm
      coupling were reduced and increased, respectively, compared to those estimated in
      the two-effector conditions (EH, EA). These results suggest that motor commands
      for different motor effectors are linked differently to achieve coordination in a
      task-dependent manner.

PMID- 18060543
TI  - Signal transduction underlying the control of urinary bladder smooth muscle tone
      by muscarinic receptors and beta-adrenoceptors.
AB  - The normal physiological contraction of the urinary bladder, which is required
      for voiding, is predominantly mediated by muscarinic receptors, primarily the M3
      subtype, with the M2 subtype providing a secondary backup role. Bladder
      relaxation, which is required for urine storage, is mediated by beta
      adrenoceptors, in most species involving a strong beta3-component. An excessive
      stimulation of contraction or a reduced relaxation of the detrusor smooth muscle
      during the storage phase of the micturition cycle may contribute to bladder
      dysfunction known as the overactive bladder. Therefore, interference with the
      signal transduction of these receptors may be a viable approach to develop drugs
      for the treatment of overactive bladder. The prototypical signaling pathway of M3
      receptors is activation of phospholipase C (PLC), and this pathway is also
      activated in the bladder. Nevertheless, PLC apparently contributes only in a very
      minor way to bladder contraction. Rather, muscarinic-receptor-mediated bladder
      contraction involves voltage-operated Ca2+ channels and Rho kinase. The
      prototypical signaling pathway of beta-adrenoceptors is an activation of adenylyl
      cyclase with the subsequent formation of cAMP. Nevertheless, cAMP apparently
      contributes in a minor way only to beta-adrenoceptor-mediated bladder relaxation.
      BKCa channels may play a greater role in beta-adrenoceptor-mediated bladder
      relaxation. We conclude that apart from muscarinic receptor antagonists and beta
      adrenoceptor agonists, inhibitors of Rho kinase and activators of BKCa channels
      may have potential to treat an overactive bladder.

PMID- 18060546
TI  - Ultrasound and MRI findings in appendicular and truncal fat necrosis.
AB  - OBJECTIVE: The objective was to evaluate ultrasound and MRI in clinical
      appendicular and truncal fat necrosis. MATERIALS AND METHODS: Thirty-three
      patients (14 men, 19 women, median age 55, range 29-95) were retrospectively
      evaluated. Histologically, three groups were seen: Group 1 (n = 18) consisted of
      patients with subcutaneous masses with septal and extrinsic oedema; in Group 2 (n
      = 11) necrosis occurred within lipomatous tumours and little oedema; and in Group
      3 (n = 4) there were large complex masses consistent with Morel-Lavallee lesions.
      Two experienced radiologists reviewed MR (n = 30) and ultrasound (n = 32) images
      with consensus agreement. MRI was performed on a 1.5T system with T1-weighted, T2
      weighted fat-suppressed and T1-weighted fat-suppressed post-intravenous
      gadolinium sequences obtained in two orthogonal planes. Ultrasound (linear 5- to
      13.5-MHz probe) was performed in the longitudinal and short axis. Anatomical
      position, size, shape (oval, linear, ill-defined), internal architecture
      (lobules, septi or stranding), intrinsic signal characteristics, presence of
      surrounding pseudocapsule, extrinsic linear stranding and vascularity (gadolinium
      enhancement or power Doppler) were recorded. RESULTS: Anatomical locations were
      buttock/thigh (n = 17), leg (n = 6), upper limb (n = 5) and thoracic/abdominal
      wall (n = 5) with the majority of lesions (30 out of 33) oval/linear in shape. On
      ultrasound and MRI most lesions showed internal fat lobules, intervening septi
      and a surrounding pseudocapsule. CONCLUSION: Fat necrosis can usually be
      identified as containing multiple fat lobules on ultrasound and MRI despite a
      varying degree of inflammatory change surrounding and within the mass.

PMID- 18060547
TI  - Whole body [11C]-dihydrotetrabenazine imaging of baboons: biodistribution and
      human radiation dosimetry estimates.
AB  - PURPOSE: Vesicular monoamine transporter type 2 abundance quantified using the
      radiotracer [(11)C]-dihydrotetrabenazine (DTBZ) has been used to study diagnosis
      and pathogenesis of dementia and psychiatric disorders in humans. In addition, it
      may be a surrogate marker for insulin-producing pancreatic beta cell mass, useful
      for longitudinal measurements using positron emission tomography to track
      progression of autoimmune diabetes. To support the feasibility of long-term
      repeated administrations, we estimate the biodistribution and dosimetry of
      [(11)C]-DTBZ in humans. METHODS: Five baboon studies were acquired using a
      Siemens ECAT camera. After transmission scanning, 165-210 MBq of [(11)C]-DTBZ
      were injected, and dynamic whole body emission scans were conducted. Time
      activity data were used to obtain residence times and estimate absorbed radiation
      dose according to the MIRD model. RESULTS: Most of the injected tracer localized
      to the liver and the lungs, followed by the intestines, brain, and kidneys. The
      highest estimated absorbed radiation dose was in the stomach wall. CONCLUSIONS:
      The largest radiation dose from [(11)C]-DTBZ is to the stomach wall. This dose
      estimate, as well as the radiation dose to other radiosensitive organs, must be
      considered in evaluating the risks of multiple administrations.

PMID- 18060548
TI  - Urinary markers in screening patients with hematuria.
AB  - Hematuria is a common presenting symptom of urothelial malignancy. Although
      conventional urine analysis is very sensitive in detecting the presence of
      hematuria, it is not specific in detecting bladder cancer or other urinary-tract
      cancers. The noninvasive urinary tests NMP22 and UroVysion have been approved by
      the U.S. Food and Drug Administration for bladder cancer screening. These tests
      have better sensitivity than cytology for detecting bladder cancer in patients
      who present with hematuria. The positive predictive values of both tests increase
      in individuals with hematuria who have risk factors for bladder cancer.
      Evaluating hematuria with sensitive markers, such as NMP22 and UroVysion, in high
      risk populations offers an opportunity to develop effective strategies for
      bladder cancer screening.

PMID- 18060549
TI  - Bladder cancer markers in patient management: the current perspective.

PMID- 18060551
TI  - Mechanisms of neurodegeneration in mucopolysaccharidoses II and IIIB: analysis of
      human brain tissue.
AB  - Mucopolysaccharidoses (MPS) are inherited disorders caused by the deficiency of
      lysosomal enzymes. Sanfilippo syndrome (MPS III) and Hunter syndrome (MPS II) are
      characterized by severe and mild neurological disorders, respectively, in which
      the neurodegenerative mechanisms remain to be clarified. We immunohistochemically
      examined the involvement of tauopathy/synucleinopathy, cell death and oxidative
      damage in the brains of three cases each of MPS IIIB and MPS II and age-matched
      controls. In cases of MPS IIIB, the density of GABAergic interneurons in the
      cerebral cortex immunoreactive for calbindin-D28K and parvalbumin was markedly
      reduced when compared with age-matched controls. The swollen neurons showed
      immunoreactivity for phosphorylated alpha-synuclein but not for phosphorylated
      tau protein or beta-amyloid protein; those in the cerebral cortex demonstrated
      nuclear immunoreactivity for TUNEL, single-stranded DNA and 8-OHdG. Neither lipid
      peroxidation nor protein glycation was marked in MPS cases. The expression levels
      of superoxide dismutases (Cu/ZnSOD and MnSOD) and glial glutamate transporters
      (EAAT1 and EAAT2) were reduced in two MPS II cases. The disturbance of GABAergic
      interneurons can be related to mental disturbance, while synucleinopathy and/or
      DNA impairment may be implicated in the neurodegeneration of swelling neurons due
      to storage materials in MPS IIIB cases. These findings suggest the possibility of
      neuroprotective therapies other than enzyme replacement in MPS patients.

PMID- 18060550
TI  - Object localization through the lateral line system of fish: theory and
      experiment.
AB  - Fish acquire information about their aquatic environment by means of their
      mechanosensory lateral-line system. This system consists of superficial and canal
      neuromasts that sense perturbations in the water surrounding them. Based on a
      hydrodynamic model presented here, we propose a mechanism through which fish can
      localize the source of these perturbations. In doing so we include the curvature
      of the fish body, a realistic lateral line canal inter-pore distance for the
      lateral-line canals, and the surface boundary layer. Using our model to explore
      receptor behavior based on experimental data of responses to dipole stimuli we
      suggest that superficial and canal neuromasts employ the same mechanism, hence
      provide the same type of input to the central nervous system. The analytical
      predictions agree well with spiking responses recorded experimentally from
      primary lateral-line nerve fibers. From this, and taking into account the central
      organization of the lateral-line system, we present a simple biophysical model
      for determining the distance to a source.

PMID- 18060552
TI  - Arthroscopic treatment of a large lateral femoral notch in acute anterior
      cruciate ligament tear.
AB  - A 24-year-old professional soccer player suffered an acute anterior cruciate
      ligament tear associated with a radiologically evident impression fracture of the
      lateral femoral condyle, the so-called "lateral femoral notch sign". Following
      MRI validation of the injury with detection of an additional lateral meniscus
      tear, arthroscopy was carried out 3 days after the injury. Due to the extended
      impression of about 5 mm, arthroscopically assisted closed reduction of the
      depression fracture was performed. A 3.2 mm tunnel was drilled at the lateral
      femoral condyle in a supero-inferior direction using an ACL tibial guide and the
      depressed area could be restored using an elevator. The resulting subchondral
      bone defect in the femoral condyle was filled with freeze-dried human cancellous
      bone allograft. As a one-stage procedure ACL reconstruction was carried out using
      a hamstring tendon technique. At 1-year follow up the patient has returned to
      full sporting function, including playing soccer with a radiographically reduced
      lateral femoral notch sign.

PMID- 18060553
TI  - Solitary fibrous tumor in the cervical spine with destructive vertebral
      involvement: a case report and review of the literature.
AB  - INTRODUCTION: Recently, solitary fibrous tumors occurring in spine-related
      lesions have been reported. However, the destruction of vertebral bodies by this
      type of tumor has not been reported. MATERIALS AND METHODS: A 71-year-old female
      presented with pain from a mass on the right side of her neck. Plain radiographs
      of the cervical spine showed collapse of the C5 vertebral body and dislocation of
      the C4 vertebral body. The MRI image showed a large mass surrounding C4 and C5,
      which had low signal intensity in the T1W image and high signal intensity in the
      T2W image. At first, resection of the tumor and spinal fusion was performed by
      anterior approach. RESULTS: Histology revealed a solitary fibrous tumor with
      proliferating spindle cells. Immunohistochemistry showed positive stains for
      vimentin and CD34. One year postoperatively, a local recurrence manifested
      extensive destruction of the C4 and C5 vertebral bodies. Then, palliative surgery
      with posterior cervical instrumentation and radiation therapy were performed.
      Because the destruction proceeded and the rods were broken 2 years after, she
      underwent additional occipito-cervical instrumentation. CONCLUSIONS: This is the
      first report of a solitary fibrous tumor that involves the destruction of the
      spinal structure. An extensive destruction of the vertebral body by the solitary
      fibrous tumor needs to be aware in treating this tumor with spinal involvement.

PMID- 18060554
TI  - Infectious granulomatous laryngitis: a retrospective study of 24 cases.
AB  - The diagnostic and treatment of verrucous lesions of the larynx involves a high
      level of suspicion by the physician attending the patient. The causes may go from
      unspecific laryngitis to neoplasia and granulomatous diseases. This kind of
      lesion is uncommon and the presentation aspects may vary broadly. The lesions in
      larynx are significant source of morbidity. The onset of symptoms is insidious
      and the diagnosis is usually delayed. Symptoms include dysphonia, dyspnea,
      dysphagia and odynophagia. Proper treatment depends upon tissue biopsy,
      identification of the causative organism, and the appropriate pharmacotherapy. As
      there are few papers presenting the clinical features of infectious granulomatous
      laryngitis (IGL) as leishmaniasis, tuberculosis and paracoccidiodomycosis
      affecting the larynx, we considered important to show the experience of a big
      Brazilian Laryngology Service in dealing with this potential worldwide problem.
      We present a retrospective chart review showing our institution's experience with
      IGL focusing in the diagnostic, treatment and prognosis aspects. Twenty-four
      patients were identified. Mycobacterium tuberculosis and Paracoccidiodis
      brasiliensis accounted for ten cases each, and Leishmania braziliensis the
      remaining four. Hoarseness was the most common symptom of infection. Up to one
      third of patients with laryngeal involvement lacked laryngeal symptoms. The
      average delay from onset of symptoms to diagnosis was 7 months. All patients
      underwent direct laryngoscopy and biopsies. Caseating granulomas was the key
      histopathologic finding. Identification of the causative organism was uncommon.
      No evidence of concomitant malignancy was seen on biopsy. Despite treatment,
      almost 40% of patients had permanent sequelae of infection, including hoarseness,
      dyspnea, and dysphagia. Mycobacterium tuberculosis, P. brasiliensis, and L.
      braziliensis accounted for all cases of IGL. Patients may have laryngeal
      infection but lack laryngeal symptoms. Prompt diagnosis relies upon a high index
      of suspicion, especially when evaluating patients from endemic areas. Given the
      degree of tissue destruction, which accompanies infection, timely intervention
      may be important in the prevention of late sequelae. Despite appropriate therapy,
      a significant number of patients may have permanent sequelae of infection.

PMID- 18060555
TI  - Case report and surgical solution for nasal spine agenesis in a woman with Binder
      syndrome.
AB  - Binder syndrome is an uncommon disorder of unknown etiology. It is characterized
      by hypoplasia of the nose and maxilla and altered morphology of the associated
      soft tissue. We report a 19-year-old Binder syndrome patient with short-nose
      deformity and anterior nasal spine agenesis. We present a surgical technique for
      nasal spine agenesis treatment. We used a titanium screw without a graft, which
      supported the nasal tip and increased tip projection. As there is good soft
      tissue coverage over the screw, infection or extrusion was not encountered, and
      the patient had no complaints 1 year after surgery.

PMID- 18060557
TI  - Impact of a protective vest and spacer garment on exercise-heat strain.
AB  - Protective vests worn by global security personnel, and weighted vests worn by
      athletes, may increase physiological strain due to added load, increased clothing
      insulation and vapor resistance. The impact of protective vest clothing
      properties on physiological strain, and the potential of a spacer garment to
      reduce physiological strain, was examined. Eleven men performed 3 trials of
      intermittent treadmill walking over 4 h in a hot, dry environment (35 degrees C,
      30% rh). Volunteers wore the US Army battledress uniform (trial B), B +
      protective vest (trial P), and B + P + spacer garment (trial S). Biophysical
      clothing properties were determined and found similar to many law enforcement,
      industry, and sports ensembles. Physiological measurements included core (T (c)),
      mean skin (T (sk)) and chest (T (chest)) temperatures, heart rate (HR), and
      sweating rate (SR). The independent impact of clothing was determined by equating
      metabolic rate in all trials. In trial P, HR was +7 b/min higher after 1 h of
      exercise and +19 b/min by the fourth hour compared to B (P < 0.05). T (c) (+0.30
      degrees C), T (sk) (+1.0 degrees C) and Physiological Strain Index were all
      higher in P than B (P < 0.05). S did not abate these effects except to reduce T
      (sk) (P > S) via a lower T (chest) (-0.40 degrees C) (P < 0.05). SR was higher (P
      < 0.05) in P and S versus B, but the magnitude of differences was small. A
      protective vest increases physiological strain independent of added load, while a
      spacer garment does not alter this outcome.

PMID- 18060558
TI  - Modulation of adrenergic receptors and adrenergic functions in cold adapted
      humans.
AB  - To specify the role of adrenoceptors in mediating adrenergic functions after
      adaptation of humans to cold, effect of administration of increasing
      concentrations of beta1 and beta2 adrenomimetics (Dobutamine, Bricanyl) on
      resting metabolic rate, heart rate, systolic blood pressure, rectal and skin
      temperatures of control humans and of cold adapted winter swimmers was studied.
      Increase in metabolic rate, mediated by beta1 and beta2 adrenomimetics, was
      attenuated after cold adaptation, indicating downregulation of beta1 and beta2
      adrenoceptors. Since cold adapted humans have greater capacity of nonshivering
      thermogenesis, than that mediated by both beta1 and beta2 adrenoceptors, the role
      of other subtypes of adrenoceptors in mediating nonshivering thermogenesis is
      anticipated. Heart rate increased after administration of the beta2 agonist, but
      was not influenced by the beta1 agonist. The significance of beta2 adrenoceptors
      in mediating heart rate was depressed after cold adaptation. Data indicate that
      modifications of activity of beta adrenoceptors play crucial role in mechanisms
      responsible for adaptation of humans to cold.

PMID- 18060559
TI  - Blood pressure response to force-velocity properties of the knee-hip extension
      movement.
AB  - This study aimed to examine the effects of maximum static and dynamic forces
      during and after knee-hip extension movement on blood pressure. Blood pressure
      was measured with a combination of oscillometric and tonometry methods before,
      during, immediately after and 30 s after knee-hip extension movements performed
      under maximum isometric and various isotonic force conditions on the servo
      controlled dynamometer. The force-velocity relation of knee-hip extension
      movement was linear (r (2 ) = 0.9989), so that maximum isometric force (F (max))
      and unloaded velocity (V (max)) were obtained by extrapolation. F (max) coincided
      with measured maximum isometric force (F (0)) (F (0)/F (max) = 1.03 +/- 0.25).
      During isometric contraction, mean arterial pressure (MAP) increased to a larger
      extent and the increase was significantly higher than those during all controlled
      load range of isotonic force measurements. The magnitude of MAP response during
      maximum isometric exercise was positively correlated with both F (0) (r = 0.687,
      P < 0.01) and V (max) (r = 0.586, P < 0.05). On the other hand, there was no
      significant correlation between F (0) and V (max) (r = 0.451, P > 0.05). It is
      suggested that measurements of muscular function with isotonic trials cause
      smaller increase in blood pressure than isometric trials do. Also, it was
      indicated that individuals with greater muscular strength and speed might respond
      with larger changes in blood pressure to strenuous muscular exercises.

PMID- 18060556
TI  - Assembly, organization, and function of the COPII coat.
AB  - A full mechanistic understanding of how secretory cargo proteins are exported
      from the endoplasmic reticulum for passage through the early secretory pathway is
      essential for us to comprehend how cells are organized, maintain compartment
      identity, as well as how they selectively secrete proteins and other
      macromolecules to the extracellular space. This process depends on the function
      of a multi-subunit complex, the COPII coat. Here we describe progress towards a
      full mechanistic understanding of COPII coat function, including the latest
      findings in this area. Much of our understanding of how COPII functions and is
      regulated comes from studies of yeast genetics, biochemical reconstitution and
      single cell microscopy. New developments arising from clinical cases and model
      organism biology and genetics enable us to gain far greater insight in to the
      role of membrane traffic in the context of a whole organism as well as during
      embryogenesis and development. A significant outcome of such a full understanding
      is to reveal how the machinery and processes of membrane trafficking through the
      early secretory pathway fail in disease states.

PMID- 18060560
TI  - Mechanisms behind inter-individual differences in lung diffusing capacity.
AB  - We measured diffusing capacity (DLCO), alveolar membrane properties (D (m)),
      capillary lung volume (V (c)), and alveolar volume (V (A) ) in 20 healthy
      subjects (12 males; age 32.4 +/- 13 (SD); BMI 21.7 +/- 3; non smokers) at total
      lung capacity (TLC) and at approximately 80, 60, and 40% TLC. In all subjects, D
      (m) increased with lung volume, the increase being significantly greater for
      higher values of D (m)(TLC): the inter-individual differences can be interpreted
      by a greater number of alveolar units coupled to a lower thickness of the air
      blood barrier (thus a higher alveolar surface to thickness ratio S (A)/tau). On
      the average, the volume-dependent increase of D (m) from approximately 40 to 100%
      TLC is less than expected based on geometrical increase of S (A) /tau. In fact,
      up to approximately 80% TLC, the increase in D (m) closely reflects only the
      increase of S (A), suggesting "unfolding" of the septa with no appreciable
      decrease in tau. Conversely, above 80% TLC, the decrease in tau due to
      parenchymal stretching becomes the main factor affecting D (m). In all subjects,
      V (c) decreased with increasing lung volume, in line with an increase in
      parenchymal stretching; the decrease was significantly larger for higher values
      of V (c) (40% TLC). Possibly reflecting differences in alveolar capillary
      density. No correlation was found between D (m)(TLC) and V (c)(40%TLC). The
      individual specificity in the lung volume dependence of V (c) and D (m) can be
      reasonably described by evaluating the V (c)/D (m) ratio at TLC and at
      approximately 40%TLC.

PMID- 18060561
TI  - Resolving the dynamics of EEG generators by multichannel recordings.
AB  - The voltage recorded over the cortex (ECoG) or over the scalp (EEG) is generated
      by currents derived from many sources called "generators". Different patterns and
      amplitudes are observed in aroused, sleepy, epileptic or other brain states.
      Differences in amplitude are generally attributed to differences in synchrony
      among generators. The degree of EEG synchrony is measured by the correlation
      between electrodes placed over different cortical regions. We present a new way
      to quantitatively assess the degree of synchronization of these generators via
      multichannel recordings. We illustrate how situations where there are several
      groups of generators with different inter-group and intra-group synchronies can
      be analyzed. Finally, we present a way to identify the organization of groups
      exhibiting topographic organization. Although the model presented here is highly
      simplified, several methods are based on averaging activity over increasingly
      larger areas. These types of measurements may be applied as well to EEG and ECoG
      recordings.

PMID- 18060562
TI  - Atomic force microscopy visualises a hydrophobic meshwork in the central channel
      of the nuclear pore.
AB  - Nuclear pore complexes (NPCs) mediate and control the transport of virtually all
      material between the cytosol and the nucleus. It is, therefore, unsurprising that
      they have long taken centre stage in physiology. A precise understanding of the
      NPC structure and function that remain to be thoroughly investigated yet is,
      thus, of crucial importance. The NPC can mediate transport both actively and
      passively. It remains to be clarified, however, whether transport of small
      molecules and macromolecules proceeds through the same route in the NPC.
      Furthermore, it has been shown that surface hydrophobicity represents a major
      sorting criterion for the active transport through NPCs. Transport factors like
      importin beta, which exhibit a rather large surface hydrophobicity, bind to their
      cargo and are believed to interact with a supposedly hydrophobic meshwork that is
      assumed to reside in the central channel of the NPC but has not yet been
      visualised. This interaction is presumed to lead to a partial breakdown of the
      meshwork, thereby, permitting the transport-cargo complexes to pass through. In
      this study, by using the nano-imaging approach, atomic force microscopy, we
      visualised under near-physiological conditions, for the first time, the presence
      of a hydrophobic meshwork in the NPC central channel. Furthermore, our data lend
      strong support for the existence of two segregated transport routes in the NPC.

PMID- 18060563
TI  - DNA methylation in mouse embryonic stem cells and development.
AB  - Mammalian development is associated with considerable changes in global DNA
      methylation levels at times of genomic reprogramming. Normal DNA methylation is
      essential for development but, despite considerable advances in our understanding
      of the DNA methyltransferases, the reason that development fails when DNA
      methylation is deficient remains unclear. Furthermore, although much is known
      about the enzymes that cause DNA methylation, comparatively little is known about
      the mechanisms or significance of active demethylation in early development. In
      this review, we discuss the roles of the various DNA methyltransferases and their
      likely functions in development.

PMID- 18060564
TI  - Syntheses and characterization of vitamin B12-Pt(II) conjugates and their
      adenosylation in an enzymatic assay.
AB  - Aiming at the use of vitamin B12 as a drug delivery carrier for cytotoxic agents,
      we have reacted vitamin B12 with trans-[PtCl(NH3)2(H2O)]+, [PtCl3(NH3)](-) and
      [PtCl4](2-). These Pt(II) precursors coordinated directly to the Co(III)-bound
      cyanide, giving the conjugates [(Co)-CN-(trans-PtCl(NH3)2)]+ (5), [(Co)-CN-(trans
      PtCl2(NH3))] (6), [(Co)-CN-(cis-PtCl2(NH3))] (7) and [(Co)-CN-(PtCl3)](-) (8) in
      good yields. Spectroscopic analyses for all compounds and X-ray structure
      elucidation for 5 and 7 confirmed their authenticity and the presence of the
      central "Co-CN-Pt" motif. Applicability of these heterodinuclear conjugates
      depends primarily on serum stability. Whereas 6 and 8 transmetallated rapidly to
      bovine serum albumin proteins, compounds 5 and 7 were reasonably stable. Around
      20% of cyanocobalamin could be detected after 48 h, while the remaining 80% was
      still the respective vitamin B12 conjugates. Release of the platinum complexes
      from vitamin B12 is driven by intracellular reduction of Co(III) to Co(II) to
      Co(I) and subsequent adenosylation by the adenosyltransferase CobA. Despite
      bearing a rather large metal complex on the beta-axial position, the cobamides in
      5 and 7 are recognized by the corrinoid adenosyltransferase enzyme that catalyzes
      the formation of the organometallic C-Co bond present in adenosylcobalamin after
      release of the Pt(II) complexes. Thus, vitamin B12 can potentially be used for
      delivering metal-containing compounds into cells.

PMID- 18060565
TI  - Comparative study on the effect of ultrasonic instruments on the root surface in
      vivo.
AB  - The present study was designed to investigate the effectiveness of different
      ultrasonic instruments on the root surface. Fourteen patients with 35 single root
      teeth designated for extraction were recruited to the present study. Teeth were
      assigned to four experimental groups: group 1, piezoelectric ultrasonic device;
      group 2, magnetostrictive ultrasonic device; group 3, hand instrumentation; and
      group 4, untreated teeth (control). After instrumentation, the teeth were
      extracted and the presence of residual deposits (roughness and root surfaces
      characteristics) were analyzed. The results showed that residual deposits were
      similar in all tested groups: piezoelectric, 8.7%; magnetostrictive, 9.7%; hand
      instrumentation, 11.1% and control, 76.4%. There were statistically significant
      differences between control and all the experimental groups (p < 0.0001). With
      respect to roughness parameters evaluation, R(a) and R(z) of the roots treated
      with the different instruments showed a similar pattern (p > 0.05), but for R(t)
      and R(y), a significant difference was observed (p < 0.05) among hand
      instrumentation and ultrasonic devices. SEM analysis revealed a similar root
      surface pattern for the ultrasonic devices, but curettes showed many instrumental
      scratches, deep gouges, and a relatively large amount of dentin was removed.
      Within the limits of the study, although the instruments produced similar
      results, root surfaces instrumentated with curettes were rougher and had more
      root surface tissue removed than with the ultrasonic device.

PMID- 18060566
TI  - Birth order and the genetics of amyotrophic lateral sclerosis.
AB  - The cause of ALS remains largely unknown for the 90% with no known family
      history, but spontaneous mutation to risk alleles of as yet unidentified genes is
      possible. It has long been recognized that genetic diseases may be more likely to
      occur in the last born children of a sibship because increased paternal age is
      associated with an increased spontaneous point mutation rate in sperm. To test
      the hypothesis that such a mechanism is responsible for sporadic ALS, we have
      performed a retrospective analysis of birth order position. We have analyzed
      sibships of size greater than four using a binomial test for birth position. The
      478 pedigrees studied show no birth order effect, suggesting that any genetic
      contributions to sporadic ALS are more likely to be through deletion in large
      genes or interactions of common polymorphisms, rather than frequent spontaneous
      point mutation. This is encouraging for the prospect of finding sporadic ALS
      susceptibility genes using genome-wide association mapping.

PMID- 18060568
TI  - SNP and haplotype identification of the wheat monomeric alpha-amylase inhibitor
      genes.
AB  - Seventy-three gene sequences encoding monomeric alpha-amylase inhibitors were
      characterized from cultivated wheat "Chinese Spring", group 6 nullisomic
      tetrasomic lines of "Chinese Spring" and diploid putative progenitors of common
      wheat. The monomeric alpha-amylase inhibitors from the different sources shared
      very high homology (99.54%). The different alpha-amylase inhibitors, which were
      determined by the 24 single nucleotide polymorphisms (SNPs) of their gene
      sequences, were investigated. A total of 15 haplotypes were defined by sequence
      alignment, among which 9 haplotypes were found with only one single sequence
      sample. Haplotype H02 was found to be the main haplotype occurring in 83 WMAI
      sequence samples, followed by haplotype H11. The median-joining network for the
      15 haplotypes of monomeric alpha-amylase inhibitor gene sequences from hexaploid
      wheats was star like, and at least two subclusters emerged. Furthermore evidence
      of homologous recombination was found between the haplotypes. The relationship
      between nucleotide substitutions and the amino acid changes in WMAI of hexaploid
      wheats was summarized. It was clear that only five polymorphic sites in the
      nucleotide sequence of WMAI resulted in amino acid variations, and that should be
      the reason for different structure and function of inhibitors. However, little
      evidence could be found that there were WMAI genes in the A genome of hexaploid
      wheat, whereas it could conclude from our results that the A genome diploid wheat
      had WMAI genes. The overall information on the monomeric alpha-amylase inhibitors
      from wheat and Aegilops strongly support the view that these inhibitors have
      evolved from a common ancestral gene through duplication and mutation.

PMID- 18060569
TI  - The DNA-repair Ku70 protein is located in the nucleus and tail of elongating
      spermatids in grasshoppers.
AB  - Fluorescence immunostaining for the phosphorylated H2AX histone (gammaH2AX) in
      the grasshopper Eyprepocnemis plorans has shown abundance of gammaH2AX in the
      nuclei of round and elongating spermatids, suggesting that DNA double-strand
      breaks (DSBs) occur regularly during spermiogenesis. Immunofluorescence patterns
      for Ku70, a DNA-repair protein participating in the non-homologous end-joining
      (NHEJ) pathway, showed that this protein is present in round and elongating
      spermatids, implying that the NHEJ DNA-repair pathway operates during chromatin
      compaction in spermiogenesis. In addition, during the final stages of
      spermiogenesis, the Ku70 protein concentrates on the region forming the sperm
      tail. Since Ku70 was also abundant in spermatid tails, it is reasonable to assume
      that Ku70 might play a novel function in sperm-tail formation. The analysis of
      Ku70 immunofluorescence patterns in 13 other grasshopper species also showed the
      presence of this protein in the nucleus and tail of elongating spermatids,
      indicating that this is a general characteristic in grasshoppers.

PMID- 18060570
TI  - Chromosome neighborhood composition determines translocation outcomes after
      exposure to high-dose radiation in primary cells.
AB  - Radiation exposure is an occupational hazard for military personnel, some health
      care professionals, airport security screeners, and medical patients, with some
      individuals at risk for acute, high-dose exposures. Therefore, the biological
      effects of radiation, especially the potential for chromosome damage, are major
      occupational and health concerns. However, the biophysical mechanisms of
      chromosome instability subsequent to radiation-induced DNA damage are poorly
      understood. It is clear that interphase chromosomes occupy discrete structural
      and functional subnuclear domains, termed chromosome territories (CT), which may
      be organized into 'neighborhoods' comprising groups of specific CTs. We directly
      evaluated the relationship between chromosome positioning, neighborhood
      composition, and translocation partner choice in primary lymphocytes, using a
      cell-based system in which we could induce multiple, concentrated DNA breaks via
      high-dose irradiation. We critically evaluated mis-rejoining profiles and tested
      whether breaks occurring nearby were more likely to fuse than breaks occurring at
      a distance. We show that CT neighborhoods comprise heterologous chromosomes,
      within which inter-CT distances directly relate to translocation partner choice.
      These findings demonstrate that interphase chromosome arrangement is a principal
      factor in genomic instability outcomes in primary lymphocytes, providing a
      structural context for understanding the biological effects of radiation
      exposure, and the molecular etiology of tumor-specific translocation patterns.

PMID- 18060571
TI  - Hepatic and extrahepatic expression of estrogen-responsive genes in male adult
      zebrafish (Danio rerio) as biomarkers of short-term exposure to 17beta-estradiol.
AB  - Growing concern over reproductive hormones in the environment demands sensitive
      and efficient methods by use of molecular biomarkers to detect these contaminants
      in oviparous vertebrates. In this study, a real-time quantitative RT-PCR was
      adopted to investigate the expressions of three estrogen-responsive genes, Vtg I,
      Vtg II and ERalpha, in hepatic and extrahepatic tissues of male adult zebrafish
      exposed to varying concentrations of 17beta-estradiol (E2) for selected periods.
      Without exposure to E2, all the genes were expressed in the tissues of male
      controls with their levels being much lower than those in the respective tissues
      of female controls. The expressions of hepatic Vtg I and II mRNAs were induced
      significantly after 1-day exposure to E2 at as low as 0.25 microg L(-1).
      Significant induction in the expression of hepatic ERalpha mRNA required a higher
      E2 concentration (> or = 0.5 microg L(-1)) and a longer exposure (> or = 2 days),
      suggesting that Vtg I and Vtg II are more sensitive to E2 exposure. The induction
      of Vtg mRNA in the skin of zebrafish was also significant following a short
      exposure (1 day) to low E2 concentration (0.25 microg L(-1)), with the levels of
      Vtg I and Vtg II mRNA being increased by 25 and 5 times, respectively. These
      results suggest that Vtg I mRNA is a highly sensitive biomarker for determining
      the estrogenic effects of E2 and that the skin of zebrafish may be an appropriate
      substitute for liver for such a determination.

PMID- 18060572
TI  - Is medical education research 'hard' or 'soft' research?

PMID- 18060574
TI  - 'Transforming' self and world: a phenomenological study of a changing lifeworld
      following a cochlear implant.
AB  - After 50 years of being profoundly deaf, Patricia (Pat) finds her world
      'transformed'-literally and metaphorically-when she receives a cochlear implant.
      Her sense of self and the taken-for-granted, comfortable world she knew before
      surgery disappear and she is thrown into an alien, surreal existence full of
      hyper-noise. Entry into this new world of sounds proves a mixed blessing as Pat
      struggles to come to terms with her changing relationships, not only with others
      (who now feel somehow 'different' to her) but also with herself. On good days,
      she is exhilarated by all her sensory gains and her feeling of being more
      connected with and to the world. On bad days she is distracted and overwhelmed by
      the intrusive noise and she is forcibly confronted with the painful reality of
      her own disability (past and present). The challenge she confronts is not simply
      the cognitive-perceptual one of learning to discriminate between sounds. Pat must
      also re-orientate herself and learn to cope with her transformed self and world.
      She must undertake a journey to come to terms with her past, present and future
      being. Pat shared her story with me and together we undertook collaborative
      existential phenomenological research, co-creating a narrative of her journey
      over the year and a half following her implant. This paper presents this
      narrative followed by an existential analysis of Pat's disrupted, changing
      lifeworld.

PMID- 18060573
TI  - Evidence for positive Darwinian selection on the hepcidin gene of Perciform and
      Pleuronectiform fishes.
AB  - Hepcidin is a small cysteine-rich peptide that plays an important role in
      antimicrobial activity and in maintaining iron homeostasis in vertebrates. Here
      we report on the underlying mechanism that maintains high sequence diversities
      among the hepcidin-like variants of perciform and pleuronectiform fishes. In
      contrast to mammals, maximum likelihood-based codon substitution analyses
      revealed that positive Darwinian selection (nonsynonymous to synonymous
      substitution, omega > 1) is the likely cause of accelerated rate of amino acid
      substitutions in the hepcidin mature peptide region of these fishes. Comparison
      of models incorporating positive selection (omega > 1) at certain sites with
      models not incorporating positive selection (omega < 1) failed to reject (p = 0)
      the evidence of positive selection among the codon sites of percifom and
      pleuronectiform hepcidin. The adaptive evolution of this peptide in perciform and
      pleuronectiform fishes might be directed by pathogens when the host is exposed to
      new habitats/environments.

PMID- 18060575
TI  - Transient and sustained oxidative stress differentially activate the JNK1/2
      pathway and apoptotic phenotype in H9c2 cells.
AB  - The aim of this study was to investigate the activation of JNK1/2 signalling
      pathway and the respective cellular phenotype of H9c2 cardiac myoblasts during
      two distinct types of oxidative insult. We examined the dose- and time-dependent
      activation of JNK1/2 pathway by exogenous H2O2, both under transient and
      sustained stimulation. At 2 h of either sustained or transient treatment, maximal
      phosphorylation of c-Jun was observed, coincidently with the activation of
      nuclear JNK1/2; under sustained stress, these phosphorylation levels remained
      elevated above basal for up to 6 h, whereas under transient stress they declined
      to basal ones within 4 h of withdrawal. Furthermore, the JNK1/2 selective
      inhibitor SP600125 abolished the c-jun phosphorylation induced by oxidative
      stress. Our results using cell viability assays and light microscopy revealed
      that sustained H2O2 stimulation significantly and time-dependently decreased H9c2
      viability, in contrast to transient stimulation; SP600125 (10 microM) abolished
      cell death induced by sustained as well as cell survival induced by transient
      oxidative stress. Hoechst staining showed an increase in DNA condensation during
      sustained, but not during transient stimulation. Moreover, from the antioxidants
      tested, catalase and superoxide dismutase prevented oxidative stress-induced cell
      death. Flow cytometry studies reconfirmed that sustained oxidative stress induced
      apoptosis, whereas transient resulted in the recovery of cardiac myoblasts within
      24 h. We conclude that in H9c2 myoblasts, sustained activation of JNK1/2
      signalling pathway during oxidative stimulation is followed by an apoptotic
      phenotype, while transient JNK1/2 activation correlates well with cell survival,
      suggesting a dual role of this signalling pathway in cell fate determination.

PMID- 18060577
TI  - Scoring system for predicting malignancy in patients diagnosed with atypical
      ductal hyperplasia at ultrasound-guided core needle biopsy.
AB  - BACKGROUND: The aim of this study was to determine factors that predict under
      evaluation of malignancy in patients diagnosed with atypical ductal hyperplasia
      (ADH) at ultrasound-guided core needle biopsy (CNB), and to develop a prediction
      algorithm for scoring the possibility of a diagnosis upgrade to malignancy based
      on clinical, radiological and pathological factors. METHODS: The study enrolled
      patients diagnosed with ADH at ultrasound-guided CNB who subsequently underwent
      surgical excision of the lesion. Multivariate analysis was used to identify
      relevant clinical, radiological and pathological factors that may predict
      malignancy. RESULTS: A total of 102 patients with ADH at CNB were identified. Of
      the 74 patients who underwent subsequent surgical excision, 34 (45.8%) were
      diagnosed with invasive or in situ malignant foci. Multivariate analysis revealed
      that age>50 years, microcalcification on mammography, size on imaging>15 mm and a
      palpable lesion were independent predictors of malignancy. Focal ADH was a
      negative predictor. A scoring system was developed based on logistic regression
      models and beta coefficients for each variable. The area under the ROC curve was
      0.903 (95% CI: 0.82-0.94), and the negative predictive value was 100% for a
      score<or=3.5. Similar findings were observed for a validation dataset of 54
      patients at other institutions. CONCLUSIONS: A scoring system to predict
      malignancy in patients diagnosed with ADH at CNB was developed based on five
      factors: age, palpable lesion, microcalcification on mammography, size on imaging
      and focal ADH. This system was able to identify a subset of patients with lesions
      likely to be benign, indicating that imaging follow-up rather than surgical
      excision may be appropriate.

PMID- 18060576
TI  - N-acetylglucosaminyltransferase V mediates cell migration and invasion of mouse
      mammary tumor cells 4TO7 via RhoA and Rac1 signaling pathway.
AB  - In tumor cells, alterations in cellular glycosylation may play a key role in
      their metastatic behavior. Using small interfering RNA against GnT-V, we found
      that the expression of GnT-V and beta1,6GlcNAc branching were significantly
      reduced which was particularly accompanied by the arrest in both cell migration
      and invasion as compared to the negative control. Moreover, the suppressed GnT-V
      expression by siRNA technique inactivated the signaling molecules including Rac1,
      cofilin, Erk and Akt, and activated RhoA levels in cells lacking GnT-V, but
      revealed no impact on Cdc42 activity. All these notions disclose for the first
      time that GnT-V and beta1, 6GlcNAc branching mediate the cell migration and
      invasion in Rac1-positive and RhoA-negative regulatory manners.

PMID- 18060578
TI  - The level of hospital charges and the income of the uninsured patient.
AB  - It is a commonly held belief that full billed charges for hospital services, when
      submitted to uninsured patients, constitute such an extraordinary payment burden
      that hospitals' attempts to collect full payment are irrational. We examine that
      proposition with data on the joint distribution of hospital charges and uninsured
      incomes, guided by prevailing standards on the concept of ability-to-pay. We find
      that there is in fact a substantial intersection of charges and incomes in which
      full payment from the uninsured, or at least substantial partial payment, is a
      reasonable commercial expectation. When we quantify the estimated extent of
      charge collectability, we conclude that there is empirical support for current
      hospital collection practices.

PMID- 18060579
TI  - Effects of chlorpyrifos on macroinvertebrate communities in coastal stream
      mesocosms.
AB  - This study measured the effects of a single pulse of chlorpyrifos at nominal
      concentrations of 1 and 10 microg/l on the macroinvertebrate community structure
      of a coastal stream mesocosm system. Analysis of data using Principal Response
      Curves (PRC) and Monte Carlo tests showed significant changes in the treated
      stream mesocosms relative to that of the controls. These changes in the
      macroinvertebrate assemblages occurred within 6 h, and persisted for at least 124
      days after dosing. Significant community-level effects were detected at the
      lowest concentration on days 2 and 16 post-dosing, giving a no-observed effect
      concentration (NOEC(community)) of 1.2 microg/l (measured). The mayflies
      Atalophlebia sp. and Koorrnonga sp., Chironomidae and Acarina were all sensitive
      to chlorpyrifos and decreased in abundance in treated mesocosms after dosing. The
      fauna of these coastal stream mesocosms showed similar sensitivity to
      chlorpyrifos with that of other reported studies, but there was no evidence of
      recovery after 124 days.

PMID- 18060580
TI  - The effect of in situ cadmium contamination on some biomarkers in Cerastoderma
      glaucum.
AB  - The present study was designed to detect in situ effects of cadmium on marine
      organisms Cerastoderma glaucum from the gulf of Gabes (Tunisia). Six sampling
      stations were chosen: one site, relatively far from known local source of
      pollution, was considered as uncontaminated site and five sites clearly exposed
      to anthropogenic impact. Metallothionein like protein (MTLP) and sub-cellular
      metal partitioning were measured in cockles (C. glaucum) gills and digestive
      gland. Various biomarkers were also measured, including malondialdehyde (MDA) in
      the digestive gland and acetylcholinesterase activity (AChE) in the remainder.
      The health status of the cockles was assessed by using the condition index (CI).
      Significant differences between sites were noted for Cd concentrations, (CI) and
      also for the three studied biomarkers. Significant higher biomarkers response was
      measured in cockles from stations located in the northern part of the gulf, which
      are exposed directly to industrial and urban effluents, whereas the response of
      most biomarkers was minimal at the reference station. Positive and significant
      correlations were observed between MTLP and Cd concentrations in the digestive
      gland and in the gills. However, it must be noted that these correlations were
      more significant in the digestive gland, suggesting that compared to the gills,
      the digestive gland of C. glaucum is more suitable for monitoring metal
      pollution. The subcellular distribution of Cd showed that the soluble fraction
      was the major compartment for Cd storage, a pattern which is due to the role of
      MTLP in Cd detoxication. But at the most contaminated site (EH), cadmium in the
      digestive gland was preferentially accumulated in the insoluble fraction (P1)
      suggesting that the MTLP capacity in binding metals was not sufficient to avoid
      the binding of Cd to the insoluble fraction. Furthermore, the MTLP concentrations
      in the cockles from this site are lower than expected. So in highly polluted
      sites, MTLP in C. glaucum should not be used as a useful biomarker for metal
      pollution. The lipid peroxidation as presented by malondialdehyde levels, and MT
      like protein concentrations increased in cockles exposed to cadmium
      contamination. We can, therefore, hypothesize that Cd could induce MTLP synthesis
      and MDA increase. While AChE had distinct and specific pattern showing that
      cadmium is not the only factor of the inhibition of cholinesterase activity.
      There are other polluting inputs engendering this inhibition.

PMID- 18060581
TI  - Modeling of autonomic control in sleep-disordered breathing.
AB  - There is ample evidence to support the notion that chronic exposure to repetitive
      episodes of interrupted breathing during sleep can lead to systemic hypertension,
      heart failure, myocardial infarction and stroke. Recent studies have suggested
      that abnormal autonomic control may be the common factor linking sleep-disordered
      breathing (SDB) to these cardiovascular diseases. We have developed a closed-loop
      minimal model that enables the delineation of the major physiological mechanisms
      responsible for changes in autonomic system function in SDB, and also forms the
      basis for a noninvasive technique that enables the early detection of
      cardiovascular control abnormalities. The model is "minimal" in the sense that
      all its parameters can be estimated through analysis of the data measured
      noninvasively from a single experimental procedure. Parameter estimation is
      enhanced by broadening the frequency content of the subject's ventilatory
      pattern, either through voluntary control of breathing or involuntary control
      using ventilator assistance. Although the original form of the model is linear
      and time-invariant, extensions of the model include the incorporation of
      nonlinear dynamics in the autonomic control of heart rate, and allowing the
      transfer functions of the model components to assume time-varying
      characteristics. The various versions of the model have been applied to different
      populations of subjects with SDB under different conditions (e.g. supine
      wakefulness, orthostatic stress, sleep). Our cumulative findings suggest that the
      minimal model approach provides a more sensitive means of detecting abnormalities
      in autonomic cardiovascular control in SDB, compared to univariate analysis of
      heart rate variability or blood pressure variability.

PMID- 18060582
TI  - Potentiation of HIV-1 expression in microglial cells by nicotine: involvement of
      transforming growth factor-beta 1.
AB  - HIV-1 infection and nicotine addiction are global public health crises. In the
      central nervous system, HIV-1 causes a devastating neurodegenerative disease. It
      is well recognized that microglial cells play a pivotal role in the
      neuropathogenesis of HIV-1 and that drugs of abuse not only contribute to the
      spread of this agent but may facilitate viral expression in these brain
      macrophages. Nicotine has been shown to stimulate the production of HIV-1 by in
      vitro-infected alveolar macrophages, and the HIV-1 protein gp120 binds to
      nicotinic receptors. In this study, we demonstrated the constitutive expression
      of nicotinic acetylcholine receptor mRNA in primary human microglial cells and
      showed that the pretreatment of microglia with nicotine increased HIV-1
      expression in a concentration-dependent manner, as measured by p24 antigen levels
      in culture supernatants. We also found that nicotine robustly altered the gene
      expression profile of HIV-1-infected microglia and that the transforming growth
      factor-beta1 is involved in the enhanced expression of HIV-1 by nicotine.

PMID- 18060583
TI  - Colorado longitudinal twin study of reading disability.
AB  - The primary objectives of the present study are to introduce the Colorado
      Longitudinal Twin Study of Reading Disability, the first longitudinal twin study
      in which subjects have been specifically selected for having a history of reading
      difficulties, and to present some initial assessments of the stability of reading
      performance and cognitive abilities in this sample. Preliminary examination of
      the test scores of 124 twins with a history of reading difficulties and 154 twins
      with no history of reading difficulties indicates that over the 5- to 6-year
      interval between assessments, cognitive and reading performance are highly
      stable. As a group, those subjects with a history of reading difficulties had
      substantial deficits relative to control subjects on all measures at initial
      assessment, and significant deficits remained at follow-up. The stability noted
      for all cognitive and achievement measures was highest for a composite measure of
      reading, whose average stability correlation across groups was 0.80. Results of
      preliminary behavior genetic analyses for this measure indicated that shared
      genetic influences accounted for 86% and 49% of the phenotypic correlations
      between the two assessments for twin pairs with and without reading difficulties,
      respectively. In addition, genetic correlations reached unity for both groups,
      suggesting that the same genetic influences are manifested at both time points.

PMID- 18060585
TI  - [Multicenter surgical trials recruiting in Germany. Current studies].

PMID- 18060584
TI  - From stem cells to oligodendrocytes: prospects for brain therapy.
AB  - Multiple sclerosis is an autoimmune disease that destroys myelin-forming
      oligodendrocytes of the CNS. While the damage can be partially controlled using
      anti-inflammatory cytokines and steroids, endogenous repair is insufficient to
      replace lost cells. Until now cell replenishment (transplant therapy) has been
      viewed as unlikely to succeed due to allograft rejection in this sensitized
      immune environment. However, advances in stem cell biology give new hope for
      deriving patient-specific, autologous oligodendrocytes which may tip the balance
      to favor repair. The challenge will be to engineer these cells to respond to cues
      that can target their migration into lesions for brain and spinal cord repair.

PMID- 18060586
TI  - Direct costs of osteoporosis and hip fracture: an analysis for the Mexican
      healthcare system.
AB  - This study reports the direct costs related to osteoporosis and hip fractures
      paid for governmental and private institutions in the Mexican health system and
      estimates the impact of these entities on Mexico. We conclude that the economic
      burden due to the direct costs of hip fracture justifies wide-scale prevention
      programs for osteoporosis (OP). METHODS: To estimate the total direct costs of OP
      and hip fractures in the Mexican Health care system, a sample of governmental and
      private institutions were studied. Information was gathered through direct
      questionnaires in 275 OP patients and 218 hip fracture cases. Additionally, a
      chart review was conducted and experts' opinions obtained to get accurate
      protocol scenarios for diagnoses and treatment of OP with no fracture.
      Microcosting and activity-based costing techniques were used to yield unit costs.
      RESULTS: The total direct costs for OP and hip fracture were estimated for 2006
      based on the projected annual incidence of hip fractures in Mexico. A total of
      22,233 hip fracture cases were estimated for 2006 with a total cost to the
      healthcare system of US$ 97,058,159 for the acute treatment alone ($4,365.50 per
      case). We found considerable differences in costs and the way the patients were
      treated across the different health sectors within the country. CONCLUSION: Costs
      of the acute treatment of hip fractures in Mexico are high and are expected to
      increase with the predicted increment of life expectancy and the number of
      elderly in our population.

PMID- 18060587
TI  - The effects of the herbicide metolachlor on agonistic behavior in the crayfish,
      Orconectes rusticus.
AB  - Previous research suggests that agricultural herbicides interfere with olfactory
      mediated behavior, such as responses to alarm signals and the ability to locate
      food, in aquatic organisms. In crayfish, aggressive interactions are also
      mediated by chemical signals. These social signals are important in establishing
      dominance, which in turn has an impact on an individual's ability to find and use
      mates, food, and habitat space. In this study, we investigated the impact of
      exposure to sublethal levels of the herbicide metolachlor on the ability of
      crayfish to respond to olfactory signals used in agonistic behaviors. Crayfish
      were exposed to three different environmentally relevant concentrations (60 ppb,
      70 ppb, and 80 ppb) of metolachlor for 96 hours. Each exposed crayfish was then
      placed in a fight arena and was allowed to interact with a naive, untreated
      crayfish for 15 minutes. We analyzed several characteristics of fighting
      behavior, including initial aggressiveness, time to fight, intensity levels,
      duration, number of encounters, and the winner and loser of each fight. Crayfish
      exposed to 80 ppb metolachlor were less likely to initiate and win encounters
      against naive conspecifics than any other treatment group. Analysis of fight
      dynamics shows that metolachlor does not alter the temporal fighting dynamics
      within crayfish aggression. We conclude that high sublethal concentrations of
      metolachlor may be interfering with the ability of crayfish to receive or respond
      to social signals and thus affect certain agonistic behaviors.

PMID- 18060589
TI  - The complete nucleotide sequence of a novel Tobamovirus, Rehmannia mosaic virus.

PMID- 18060588
TI  - Effects of orange juice and proline betaine on glycine betaine and homocysteine
      in healthy male subjects.
AB  - BACKGROUND: Proline betaine (PB), a glycine betaine (GB) analogue found in citrus
      foods, increases urinary GB loss and plasma total homocysteine (tHcy)
      concentrations in rats. Its presence in human plasma is associated with increased
      GB excretion. AIM: To compare the effects of dietary levels of PB on GB
      excretion, and on plasma tHcy and GB concentrations in healthy volunteers.
      METHODS: In a randomized crossover study, eight healthy males (18-50 years)
      ingested either 750 mL orange juice (containing 0.545 g PB), a PB supplement
      (0.545 g PB dissolved in 750 mL apple juice), or 750 mL apple juice (control).
      Plasma PB, GB and tHcy, and urine PB, GB and creatinine concentrations were
      measured hourly for 6 h and at 24 h post-treatment. RESULTS: Plasma tHcy
      concentrations were not increased (relative to control) following ingestion of
      either orange juice or PB supplement. Both treatments produced a significant
      increase in plasma PB concentrations (P < 0.001), this effect being greater
      following orange juice compared with PB supplement (P < 0.05, 1-2 h). Urinary
      excretion of PB was greater than the control following both orange juice (P <
      0.001) and PB supplement (P < 0.001), from 2 to 24 h post-treatment. This
      increase in PB excretion was significantly greater following orange juice
      compared with PB supplement with higher peak excretion (Cmax difference, P =
      0.008). GB excretion was significantly greater following ingestion of orange
      juice compared with PB in apple juice (P = 0.007) and apple juice control (P <
      0.001) in the first 2 h post-ingestion. CONCLUSIONS: PB administered in dietary
      doses had little effect on plasma tHcy concentrations in healthy humans.
      Ingestion of PB in orange juice compared with PB alone resulted in greater
      increases in the urinary excretion of PB and GB.

PMID- 18060590
TI  - Molecular epidemiology of wild poliovirus type 1 circulation in West and Central
      Africa, from 1997 to 1999, using genotyping with a restriction fragment length
      polymorphism assay.
AB  - Virological surveillance is an important element in the Polio Eradication
      Initiative to provide information rapidly about circulating wild polioviruses.
      Molecular tools have been developed to identify the serotype of the poliovirus
      strains and whether they are of vaccine or wild origin (intratypic
      differentiation) and to perform the molecular epidemiology of wild strains. The
      main objective of this study was to show that restriction fragment length
      polymorphism (RFLP) is a tool that can be used for molecular epidemiology of wild
      polioviruses. This is retrospective study of poliovirus type 1 strains received
      at the Institut Pasteur of Bangui (IPB), a WHO Regional Reference Laboratory for
      Africa, since 1994. We describe our experience with isolates from Western and
      Central Africa and show a positive correlation between the genotypes as
      determined by sequencing the gene for the VP1 capsid protein and the RFLP
      patterns. Although genomic sequencing is the gold standard method for detailed
      molecular epidemiology analysis of poliovirus isolates, these results show that
      RFLP is a potentially valuable tool for molecular epidemiological analysis of
      poliovirus type 1 strains: it could be used by many laboratories as a rapid
      method for ITD and genotype screening where sequencing capacity is not readily
      available.

PMID- 18060591
TI  - Nicorandil-induced severe perianal ulceration.
AB  - BACKGROUND: Nicorandil is a potassium channel activator used in the prevention
      and long-term treatment of angina pectoris. It is widely prescribed and its use
      is supported by data from powerful randomised controlled trials. The colorectal
      community is becoming increasingly aware of a subgroup of patients with anal
      ulceration and other gastrointestinal manifestations of nicorandil use. METHODS:
      This study is a retrospective review of patients identified as having nicorandil
      induced perianal ulceration. We report our experience of 11 patients. RESULTS:
      All eleven patients experienced severe debilitating ulceration of the perianal
      area and perineum. Multiple therapies were tried unsuccessfully before the
      association with nicorandil was recognised. Upon recognition of the association
      of nicorandil with these ulcers, the therapy was stopped resulting in resolution
      of the perianal symptoms. CONCLUSIONS: Nicorandil is a rare cause of severe
      perianal ulceration. This association should be recognised as these ulcers are
      resistant to other forms of treatment but heal well on ceasing nicorandil use.

PMID- 18060593
TI  - Angular tuning of defect modes spectrum in the one-dimensional photonic crystal
      with liquid-crystal layer.
AB  - A one-dimensional ZrO(2)/SiO(2) photonic crystal with a 4-n -pentyl-4' 
      cyanobiphenyl (5CB) nematic defect layer was used to investigate the transmission
      spectra of light polarized parallel and perpendicular to the liquid-crystal
      director at different angles of incidence. The spectra of the photonic crystal
      were shown to split into four polarized components T(ij) at oblique incidence.
      When the incident angle increased, the bandgap edges and the defect modes shifted
      towards short wavelengths, while the amplitudes of the defect modes increased for
      the transverse magnetic polarization and decreased for the transverse electric
      polarization. The observed discrepancy between the defect mode amplitudes in the
      center and near the edges of the photonic bandgap was found to be related to the
      radiation losses inside the defect layer of a non-ideal photonic crystal. The
      simulated transmission spectra obtained using recurrence relations and taking
      into account the decay of defect modes are in good agreement with the
      experimental data.

PMID- 18060592
TI  - The ProTect device in the treatment of severe fecal incontinence: preliminary
      results of a multicenter trial.
AB  - BACKGROUND: Patients suffering from severe fecal incontinence (FI) in whom
      surgical treatment has either failed or is inappropriate due to high operative
      risks and those who refuse to undergo surgery are condemned to living with their
      embarrassing symptoms, often responsible for progressive social isolation.
      ProTect is a new, relatively simple, medical device intended for selected
      patients suffering from severe FI. It consists of a pliable, silicone catheter
      with an inflatable balloon that seals the rectum at the anorectal junction,
      acting like an anal plug. The proximal part of the catheter incorporates two
      contacts that monitor the rectum for the presence of feces. The patient is
      alerted to an imminent bowel movement and, hence, a potential fecal accident,
      through a beeper. METHODS: A multicenter trial has been set up to assess the
      reliability of the device in preventing episodes of FI and to evaluate its impact
      on quality of life. Patients with significant FI (CCF>10) were prospectively
      entered into this 14-day study. Two quality of life questionnaires and a daily
      log of bowel activity and incontinent episodes were completed before and during
      the study. RESULTS: Currently, the study enrolled 17 patients and 11 patients (9
      women, 2 men) with a mean age of 66 years (range, 46-85) completed the trial. In
      these 11 subjects, there was an overall significant improvement in the quality of
      life (p<0.05) and a significant reduction in incontinence scores (p<0.001) while
      using ProTect compared to baseline. CONCLUSIONS: The ProTect is a safe non
      surgical device that is able to prevent episodes of FI. It is unique because it
      can be used according to a patient's needs without interfering with activities of
      daily living.

PMID- 18060594
TI  - Counterion vibrations in the DNA low-frequency spectra.
AB  - The vibrations of univalent metal cations with respect to phosphate groups of the
      DNA backbone are described using the four-mass model approach (S.N. Volkov, S.N.
      Kosevich, J. Biomol. Struct. Dyn. 8, 1069 (1991)) extended in this paper. The
      force constant of the counterion-phosphate interaction is determined by
      considering the DNA with counterions as a lattice of ion crystal. For such ion
      phosphate lattice the Madelung constant and the dielectric constant are
      estimated. The obtained value of the Madelung constant is lower than for the NaCl
      crystal, and its value is about 1.3. The dielectric constant is within 2.3-2.7
      depending on the counterion type and form of the double helix. The calculations
      of the low-frequency spectra show that for the DNA with metal cations Na(+) ,
      K(+) , Rb(+) and Cs(+) the frequency of ion-phosphate vibrations decreases from
      174 to 96 cm(-1) as the counterion mass increases. The obtained frequencies agree
      well with the vibrational spectra of polynucleotides in a dry state which prove
      our suggestion about the existence of the ion-phosphate lattice around the DNA
      double helix. The amplitudes of conformational vibrations for DNA in B -form are
      calculated as well. The results demonstrate that light counterions ( Na(+) do not
      disturb the internal dynamics of the DNA. However, heavy counterions ( Cs(+) have
      effect on the internal vibrations of the DNA structural elements.

PMID- 18060595
TI  - Life and death of a fakir droplet: impalement transitions on superhydrophobic
      surfaces.
AB  - We show that the equilibrium state of a water drop deposited on a
      superhydrophobic surface cannot be solely determined by its macroscopic contact
      angle but also depends on the drop size. Following the evolution of the interface
      of evaporating droplets, we demonstrate that the liquid can explore a succession
      of equilibrium conformations which are neither of the usual fakir nor Wenzel
      types. A comprehensive description of the transition between these wetting states
      is provided. To do so, we have taken advantage of microfabrication techniques and
      interference microscopy which allows for the "3D" imaging of the liquid
      interface. In addition, we propose a simple theoretical description of the
      interface geometry which goes beyond the standard two-state picture for
      superhydrophobicity. This model accounts correctly for all our experimental
      observations. Finally, guided by potential microfluidic applications we propose
      an efficient design strategy to build robust liquid repellant surfaces.

PMID- 18060596
TI  - Rotation of single crystals of chiral dopants at the top of a nematic droplet:
      analogy with Lehmann effect.
AB  - Detailed studies are reported of the Lehmann-type effect of rotation of small
      single crystals of chiral substances during their dissolution at the top of a
      nematic droplet, which was first noted in our previous works. The rotation effect
      is shown to be essentially dependent on the dopant chirality. The angular
      velocity of the rotation of the chiral dopant crystals is experimentally shown to
      be dependent on the crystal dimensions, helical-twisting power of the dopant
      (determined in independent measurements) and viscosity of the nematic solvent,
      whereas no rotation was observed for non-chiral dopants or in isotropic solvents
      under the same conditions. For systematic series of dopants (e.g., cholesterol
      esters), the angular velocity was proportional to the helical-twisting power;
      with different nematic matrices, the observed angular velocity was proportional
      to the rotational-viscosity coefficient gamma(1) ; also, in a certain size range,
      it was inversely proportional to the characteristic linear dimension of the
      dissolved crystal. Basing on unit dimensions arguments, a semi-empirical equation
      is proposed giving a common quantitative description of the whole set of
      experimental data obtained. It is argued that the obtained results a) suggest a
      novel method for the evaluation of the helical-twisting power, especially useful
      for dopants of weak chirality, and b) that they are a direct evidence of
      transformation of the energy of chiral interactions into the energy of the
      molecular movement.

PMID- 18060597
TI  - Food conditions, competitive regime, and female social relationships in Japanese
      macaques: within-population variation on Yakushima.
AB  - Feeding conditions, competitive regime, and female social relationships of
      Japanese macaques (Macaca fuscata) on Yakushima were compared between the two
      habitats at two different altitudes (coniferous forest, 1,000-1,200 m and coastal
      forest, 0-200 m). Fruit availability was higher in the coastal forest. There was
      no consistent difference in the frequency of agonistic interactions within a
      group during feeding between the two habitats. The coastal forest evoked stronger
      inter-group contest competition compared to the coniferous forest as evidenced by
      a higher inter-group encounter rate and a higher proportion of aggressive
      encounters to non-aggressive ones. Birth rate was higher in larger groups
      compared to smaller ones in the coastal forest, but did not differ in the
      coniferous forest. In spite of these differences in competitive regime, no
      variation in female social relationships was observed, such as direction and
      concentration on particular individuals in grooming, linearity in dominance rank,
      counter-attack, and support of juvenile kin during agonistic interactions. The
      present results indicate that the female social relationships of Japanese
      macaques are robust and do not change according to changes in the current
      environment.

PMID- 18060598
TI  - A phase I-II study of oblimersen sodium (G3139, Genasense) in combination with
      doxorubicin in advanced hepatocellular carcinoma (NCI # 5798).

PMID- 18060599
TI  - The combination of gamma ionizing radiation and 8-Cl-cAMP induces synergistic
      cell growth inhibition and induction of apoptosis in human prostate cancer cells.
AB  - The antiproliferative and cytotoxic potential of the nucleotide analog 8-Cl-cAMP
      was tested in PC-3 and DU145 metastatic human prostate cancer cells. The drug was
      examined as the only therapeutic agent and in combination with ionizing
      irradiation (IR). Highly synergistic effects of IR and 8-Cl-cAMP were observed in
      both cell lines when examined by the MTT viability and BrdU proliferation assays.
      The combination of IR and 8-Cl-cAMP at clinically relevant doses exerted
      substantial growth inhibition. The combination of IR and 8-Cl-cAMP caused a
      significant disturbance in the distribution of cell cycle phases. Cell cycle
      arrest in the sub-G0/G1 phase predominated in both cell lines. The most striking
      observation was a significant increase in apoptotic PC-3 and DU145 cells. The
      DU145 cells were three times more sensitive to the combined treatment than PC-3
      cells. The initial resistance to IR-induced apoptosis in these p53-deficient
      prostate cancer cell lines was overcome through an alternative proapoptotic
      pathway induced by 8-Cl-cAMP. Considering the low effective doses of treatments,
      improved tumor eradication rates and minimal undesirable side effects, the
      combination of IR and 8-Cl-cAMP could be the therapy of choice in treating
      prostate cancer.

PMID- 18060600
TI  - Response of preclinical medulloblastoma models to combination therapy with 13-cis
      retinoic acid and suberoylanilide hydroxamic acid (SAHA).
AB  - PURPOSE: Current medulloblastoma therapy, surgery, radiation, and chemotherapy,
      is unacceptably toxic. However, 13-cis retinoic acid (RA) and SAHA, a histone
      deacetylase inhibitor, have each been shown to induce apoptosis in
      medulloblastoma cultures and mouse models. Both drugs cross the blood brain
      barrier, have been given safely to children, and achieve brain concentrations
      that are at or near therapeutic levels. Retinoic acid acts by transcriptionally
      activating bone morphogenetic protein-2 (BMP-2) and SAHA facilitates
      transcriptional activity through chromatin accessibility. We tested the
      hypothesis that these drugs additively induce BMP-2 transcription and apoptosis.
      EXPERIMENTAL DESIGN: RA + SAHA induction of BMP-2 transcription and apoptosis in
      medulloblastoma cultures was evaluated. Subsequently the response of mouse
      medulloblastomas to these two agents in the presence and absence of cisplatin was
      evaluated. RESULTS: BMP-2 transcription multiplied 3-fold with addition of RA to
      culture, and 7-fold with both agents. The IC50 of SAHA was reduced by 40% when
      low dose RA was added. Interestingly, a p38 MAP kinase inhibitor that partially
      blocks RA-induced apoptosis did not inhibit the activity of RA + SAHA. Flank D283
      tumors in athymic mice had slower growth in the RA + SAHA arm than single drug or
      control arms. Intracranial tumors in ND2:SmoA1 mice treated with RA + SAHA +
      cisplatin showed a 4-fold increase in apoptosis over controls, and a 2-fold
      increase over animals receiving only SAHA or RA + SAHA. CONCLUSIONS: RA + SAHA
      additively induce BMP-2 transcription and medulloblastoma apoptosis. The
      combination may act through a p38 MAPK independent mechanism. Efficacy increased
      with cisplatin, which has implications for clinical trial design.

PMID- 18060601
TI  - Spectroscopic investigations of U(VI) species sorbed by the green algae Chlorella
      vulgaris.
AB  - The green alga Chlorella vulgaris has the ability to bind high amounts of
      uranium(VI) in the pH range from 3 to 6. At pH 3 up to 40% of the uranium are
      bound by the algal cells. The uranium removal is almost complete at pH 5 and 6
      under the given experimental conditions. Scanning electron microscopy and laser
      induced fluorescence spectroscopy were used to characterize uranyl species formed
      in the selected pH range. The micrographs show a regular distribution of U(VI) on
      the cell surface. Fluorescence spectroscopic investigations of formed algal
      uranyl complexes indicate that the binding of U(VI) to carboxyl groups plays a
      dominating role at pH 3, whereas a minor impact of organic phosphate compounds on
      the U(VI) sorption cannot be excluded. In contrast, at pH 5 and 6 the phosphate
      groups are mainly responsible for the removal and binding of U(VI) by formation
      of organic and/or inorganic uranyl phosphates.

PMID- 18060602
TI  - Improvement of the anaerobic treatment of potato processing wastewater in a UASB
      reactor by co-digestion with glycerol.
AB  - The effect of three different types of glycerol on the performance of up-flow
      anaerobic sludge blanket (UASB) reactors treating potato processing wastewater
      was investigated. High COD removal efficiencies were obtained in both control and
      supplemented UASB reactors (around 85%). By adding 2 ml glycerol product per
      liter of raw wastewater, the biogas production could be increased by 0.74 l
      biogas ml(-1) glycerol product, which leads to energy values in the range of 810
      1270 kWh(electric) per m(3) product. Moreover, a better in-reactor biomass yield
      was observed for the supplemented UASB reactor (0.012 g VSS g(-1) COD(removed))
      compared to the UASB control (0.002 g VSS g(-1) COD(removed)), which suggests a
      positive effect of glycerol on the sludge blanket growth.

PMID- 18060603
TI  - Stereoselective oxidation of racemic 1-arylethanols by basil cultured cells of
      Ocimum basilicum cv. Purpurascens.
AB  - The biotransformation of racemic 1-phenylethanol (30 mg) with plant cultured
      cells of basil (Ocimum basilicum cv. Purpurascens, 5 g wet wt) by shaking 120 rpm
      at 25 degrees C for 7 days in the dark gave (R)-(+)-1-phenylethanol and
      acetophenone in 34 and 24% yields, respectively. The biotransformation can be
      applied to other 1-arylethanols and basil cells oxidized the (S)-alcohols to the
      corresponding ketones remaining the (R)-alcohols in excellent ee.

PMID- 18060604
TI  - [Integrated health care].

PMID- 18060605
TI  - [Integrated care successfully optimizes the pathway of care. Positive outcomes
      through consistent clinical pathways].
AB  - The care of patients suffering from heart diseases has been embodied in the scope
      of activities of the AOK Rheinland/Hamburg since the beginning of Integrated
      Care, not least because of the relevant number of people suffering from
      cardiovascular dis eases. There are many stations to pass from the idea via
      conception to its implementation. However, this path seems to be worth treading.
      Following initial, extensive negotiations -- particularly in terms of conception 
      -, the first data collected is clear. Realization of projects regarding
      myocardial infarction, coronary heart disease/diabetes and acute coronary
      syndrome shows that obligatory clinical pathways against the background of
      guidelines can still save lives.

PMID- 18060606
TI  - [Comprehensive care: CVD and diabetes mellitus].
AB  - Diabetes and cardiovascular diseases (CVD) often appear as two sides of a coin.
      Diabetologists and cardiologists join their forces in a supply grid to improve
      the quality management in diagnosis and care in accordance with section 140a-d
      SGB V in the version from January 1, 2004. An algorithm was developed to help
      discover CVD in patients with diabetes and vice versa the metabolic diseases in
      patients with CVD, setting the basis for appropriate joint therapy.

PMID- 18060607
TI  - [New models to improve supply in patients with chronic heart failure].
AB  - Frequency of chronic heart failure still increases. More and more resources have
      been required for the diagnosis and therapy of this disease. This burden for
      health-care systems will grow in the near future. In particular, clinical
      treatment has a major impact. New approaches are essential to ensure an efficient
      supply of patients with chronic heart failure in the next years. Models to
      improve the supply give the opportunity to optimize the medical workflow and
      involve the patient into the concept of care. Therefore, a variety of models have
      been developed and up to now tested concerning benefit and applicability in
      western industrial countries. The present article focuses on the fundamental
      models to improve the supply of patients with chronic heart failure.

PMID- 18060608
TI  - [Telemetric care of patients suffering from chronic heart failure with special
      reference to the Telemetric Care and Education Program "Telemedizin furs Herz"
      ("Telemedicine for the Heart")].
AB  - Chronic heart failure (CHF) is one of the most common diagnoses in internal
      medicine. It frequently results in a considerable loss of patient quality of life
      and is affected by improvable deficits regarding managed care, diagnosis, and
      treatment. Integrated care conceptions with telemetric support for persons
      concerned have proven to ameliorate the mentioned deficits. Apart from the
      resulting medical benefits, another significant advantage of such approaches is a
      reduction of costs of treatment and care for CHF patients due to a decrease in
      hospitalizations, which account for the better part of total costs. In this
      context the non-profit-making German foundation for chronic heart cases
      ("Deutsche Stiftung fur chronisch Herzkranke") has, in cooperation with the
      statutory health insurance "Techniker Krankenkasse", developed an integrated,
      telemetric care and education program for patients suffering from CHF. Since
      January 2006, the conception stands open to all insurants of the participating
      health insurance. A growing number of patients, momentarily 431, has been
      inscribed and takes advantage of this program. The 27-month program seeks for
      integration of all participating health-care providers. Patients are, by frequent
      nurse-mediated telephone contact under supervision of physicians, intensely and
      individually cared for. Throughout the program all patients take advantage of
      repetitive teaching regarding individually relevant aspects of CHF. Subject to
      the severity of their condition, the patients are, with telemetric support,
      motivated to implement daily self-measurements of weight, blood pressure and
      pulse into their everyday life. In the course of every telephone contact greatest
      care is given to convey knowledge about limit values of measured parameters and
      symptoms of decompensation on the basis of the acquired data. Participating
      practicing physicians are regularly informed about the progress of their patients
      and, if necessary, encouraged to enhance adequate, guideline- and evidence-based
      pharmacological therapy. By means of interaction of all these program features
      and subject matters, patients are, beyond the end of the program, empowered to
      enduringly and self-dependently deal with their chronic disease. Intermediate
      data suggest that participation of CHF patients in the depicted program is, among
      other effects, able to decrease hospitalizations, optimize treatment, increase
      quality of life, and decrease mortality.

PMID- 18060609
TI  - [New health care delivery model in cardiology -- Myocardial Infarction Network
      Essen].
AB  - Current guidelines favor primary percutaneous coronary intervention (PCI) as the
      strategy of choice for the treatment of acute ST segment elevation myocardial
      infarction (STEMI). Already in its 1st year, the myocardial infarction network
      "Herzinfarktverbund Essen" demonstrates with 489 patients the feasibility of an
      exhaustive urban STEMI network with preference to patient transfer to high-volume
      PCI centers. Furthermore, integrated health care as an optional part of the
      "Herzinfarktverbund" offers reimbursement for modern and innovative diagnostic
      procedures, therapies, and rehabilitation.

PMID- 18060610
TI  - [Treatment of acute ST Elevation myocardial infarction in a regional network
      ("Drip & Ship Network Rostock")].
AB  - Management of acute ST elevation myocardial infarction (STEMI) demands rapid and
      complete reperfusion of the infarct-related artery (IRA). With postinfarction
      prognosis depending on time delay from onset of symptoms to complete reperfusion
      (TIMI 3 flow) of the IRA, primary percutaneous coronary intervention (PPCI)
      performed by an experienced team has been shown to be superior to thrombolytic
      therapy with lower mortality, less frequent occurrence of nonfatal reinfarction
      and stroke, and thus represents the preferred treatment strategy according to the
      national and international guidelines. For regional implementation of PPCI,
      particularly in rural areas, information and transfer logistics within networks
      of care and direct transport of an infarction patient to a PCI hospital rather
      than to the closest hospital are a challenge. With successful implementation of
      network logistics and standardized therapeutic pathways, current guidelines and
      requested timelines versus thrombolysis could be met. The implemented logistics
      comprised 24 h/7 days stand-by services of an experienced PCI team, direct
      telephone hotline contact between rescue service/emergency physician and
      interventional cardiologist on call, and direct open access to a catheterization
      laboratory at any time. Within the Drip&Ship network Rostock, to date (July 2007)
      1,022 consecutive patients with PCI for STEMI were documented and analyzed over 5
      years; of these, 490 patients were transferred from a community hospital to the
      PCI center and 532 patients were admitted directly to the interventional center.
      In 95.1% of all transferred and in 94.8% of all directly admitted patients, PCI
      was successfully accomplished upon arrival. A normalized flow to the IRA after
      PCI was documented in 96% of both groups, no patient was subjected to
      thrombolytic therapy. At 12-month follow-up, there were no differences between
      both groups with respect to infarct size and mortality. Moreover, there was no
      evidence of differences in left ventricular ejection fraction between groups.
      Thus, transportation of STEMI patients within an established PCI network did not
      result in any prognostic disadvantage. Efficient network logistics with
      transportation for PPCI in acute STEMI ensure both safety and outcome profiles
      similar to patients treated by PCI in metropolitan areas.

PMID- 18060611
TI  - [Telemonitoring of cardiovascular diseases in Germany. Standing position and
      perspectives].
AB  - The changes in the demographic structure, the increasing multimorbidity in
      connection with a rise in the number of chronic illnesses and the absence of an
      effective coordination of the different levels of healthcare services with its
      discontinuous processes and redundancies will lead to intolerable economic
      burdens in the German health-care system, affecting medical, health-political and
      economic dimensions alike. This is the significance in terms of content and
      strategy of "health telematics" as an application of modern telecommunication and
      information technologies in the health-care system, and of "E-Health" as a
      specification of all services, quality improvements and rationalization effects,
      which are achievable by digitizing data collection as well as communication
      processes. Not only do digitizing and electronic transmission offer a better,
      faster and safer way of communication, but by possibilities of combining data
      they also allow the rationalization and quality-improving introduction of new
      methods of diagnosis, therapy and aftercare. The latest developments and
      appropriate logistic premises nowadays offer a realistic basis for implementing
      telemonitoring as a central service and information tool as well as an instrument
      controlling the information and data flow between patient, hospital and medical
      practitioner. Considering the enormous significance of cardiovascular diseases,
      focusing on corresponding cardiologic disease patterns seems almost self-evident.
      Notwithstanding remarkable medical progress during the past few years,
      cardiovascular diseases are still the number one cause of death in industrialized
      countries. In the cardiologic sector, telemedical systems are most commonly used
      with patients suffering from coronary heart diseases, e.g., for the detection of
      unclear dysrhythmia, as well as with patients suffering from chronic heart
      failure. Seen from a medical point of view, it is paramount to judge the clinical
      situation without delay as well as to take necessary therapeutic measures timely
      and to control their efficiency over a long period of time.Consequently,
      telemedical projects include the establishment of a nonstop monitoring of
      patients with increased or high risk of cardiovascular incidents, starting with
      the hospitalization, postoperative/post in-house health care and up to home care.
      This kind of monitoring needs to be adjustable to the respective situation
      modularly in order to guarantee a smooth possibility of surveillance both in the
      stationary and the ambulant sector, which, in addition, has to be individually
      adjustable to the demand of required monitoring functions (heart rate, blood
      pressure, S-T segments, oxygen satiation, weight, breathing rate, and
      temperature) and the intensity of the monitoring (event recording, "on-demand"
      vs. continuous monitoring). Certainly rich in meaning for the future is the
      integrated telemedicine care of a "primary" cardiac patient with his relevant
      comorbidities: diabetes and coagulation monitoring, respectively.

PMID- 18060612
TI  - Sirolimus-eluting versus bare-metal stents for the reduction of coronary
      restenosis: 18-month angiographic results from the GERSHWIN Study.
AB  - PURPOSE: The GERSHWIN study (German Stent Health Outcome and Economics Within
      Normal Practice) was designed to evaluate long-term effects of treatment of
      coronary artery disease (CAD) with sirolimus-eluting stents (SES), as compared to
      bare-metal stents (BMS). PATIENTS AND METHODS: Within a multicenter, prospective
      intervention study in 35 hospitals throughout Germany, CAD patients with coronary
      stenosis and elective percutaneous coronary intervention (PCI) indication were
      treated either with SES or BMS (sequential control design with a case-to-control
      ratio of 2 : 1). Standardized questionnaires were completed by patients and their
      physicians at baseline, 3, 6, 12, and 18 months following PCI to document re-PCI
      for restenosis, myocardial infarction (MI), coronary bypass surgery (CABG), and
      death. Angiographic PCI documentation was evaluated by an independent expert.
      RESULTS: From April 2003 until June 2005, 658 patients were treated with SES
      (mean age 63 +/- 9 years, 87% male) and 294 patients with BMS (mean age 64 +/- 10
      years, 79% male). Significant baseline differences were found by age, gender,
      household status, three vessel disease, and number of implanted stents. After 18
      months, 8% of the SES versus 17% of the BMS group had undergone target vessel
      revascularization (p adjusted < 0.0001). There were no significant differences
      between BMS and SES regarding MI, CABG, or death. Re-PCI of target and new non
      target vessel lesions was performed at a significantly lower degree of stenosis
      in SES than in BMS. CONCLUSION: Compared to patients with BMS, patients with
      implantation of SES experienced considerably fewer target vessel
      revascularizations. The threshold to perform re-PCI appeared lower in SES than in
      BMS. An extended evaluation of the effects of SES will be available from the 3
      year follow-up of the GERSHWIN study.

PMID- 18060613
TI  - Are anomalies of the caval veins more common in complex congenital heart disease?
AB  - BACKGROUND AND PURPOSE: Anomalies of the caval veins are considered to be common
      cardiac malformations. The knowledge of the varieties of the caval venous system
      is essential for cardiovascular surgery, pacemaker implantation, intensive care
      medicine or cardiac catheterization. The authors wanted to know, if anomalies of
      the caval veins are related to the type and complexity of congenital heart
      disease. MATERIAL AND METHODS: The records of 1,631 patients who were
      catheterized between 1991 and 2003 were reviewed. RESULTS: 92 of these had
      anomalies of either the superior or inferior caval vein. 23 had simple congenital
      heart disease, while in 69 this was considered to be complex (p < 0.001).
      Embryologic considerations are discussed. CONCLUSION: It could be proven that
      anomalies of the caval veins are more often related to complex congenital heart
      disease. Embryologic considerations show at least a coincidence of the
      development of the caval veins and of congenital heart disease. For clinical work
      with these patients the knowledge of these anomalies is important.

PMID- 18060614
TI  - [An unusual cause of recurrent chest pain in a highly trained recreational
      athlete].
AB  - ANAMNESIS: Here, the case of a 48-year-old highly trained patient without classic
      myocardial risk factors is described who reported on frequent and recurrent
      angina pectoris. In a previous examination, the test for cardiac troponin T
      (cTnT) was slightly positive, however, cardiac examination including myocardial
      perfusion scintigraphy and coronary catheterization was without pathologic
      findings. Worth mentioning in the past medical history was a rheumatoid arthritis
      with persistent Raynaud's symptoms and hemoglobin as well as hematocrit levels in
      the upper normal range. EXAMINATIONS AND COURSE OF EVENTS: The patient reported
      that symptoms would occur most likely during long-term endurance exercise.
      Therefore, a bicycle ergometry with 180 W and open ending was performed. After
      1.55 h, the patient complained of severe angina pectoris. The ECG showed massive
      ST segment elevations in II, III, and aVF (Figure 2). However, coronary
      catheterization showed no major stenosis or occlusion. Nevertheless, cTnT
      increased to 0.979 ng/ml. (Therefore, the reason for the symptomatic ST elevation
      was believed to be a myocardial tissue damage due to coronary vasospasm and the
      patient received an antivasospastic medication (amlodipine, atorvastatin, and
      acetylsalicylic acid [ASS]). After 6 months, the patient had a relapse during
      moderate physical activity. The ECG showed an ST segment depression in V(4) and
      V(5) while markers for myocardial tissue damage including cTnT were negative. A
      coronary CT angiography was performed that revealed a subtotal stenosis of the
      proximal LAD (Fig ure 3), which was successfully treated by angioplasty with
      subsequent stenting. In the course of further examinations, a polycythemia vera
      (JAK2-V617 mutation) was diagnosed as the cause for the high hemoglobin and
      hematocrit levels. Since then, the patient was without further events under a
      medication consisting of ASS, atorvastatin, candesartan, and intermittent
      phlebotomy. CONCLUSION: Although a relative weighting is difficult, it can be
      assumed that the combined effects of a polycythemia- associated
      hypercoagulability, an increased reagibility of the coronary arteries (aggravated
      by physical stress) as well as a hemoconcentration following prolonged exercise,
      could account for symptomatic recurrent minor thrombotic coronary events as well
      as the subtotal occlusion of the LAD. Obviously, this could not be prevented by a
      healthy lifestyle, regular physical activity, and the absence of classic coronary
      risk factors.

PMID- 18060615
TI  - Protection of INS-1 cells from free fatty acid-induced apoptosis by inhibiting
      the glycogen synthase kinase-3.
AB  - To examine the role of glycogen synthase kinase 3 (GSK-3) in the apoptosis of
      pancreatic beta-cells to better understand the pathogenesis and to find new
      approach to the treatment of type 2 diabetes, apoptosis was induced by oleic acid
      (OA) in INS-1 cells and the activity of GSK-3 was inhibited by LiCl. The PI
      staining and flow cytometry were employed for the evaluation of apoptosis. The
      phosphorylation level of GSK-3 was detected by Western blotting. The results
      showed that OA at 0.4 mmol/L could cause conspicuous apoptosis of INS-1 cells and
      the activity of GSK-3 was significantly increased. After the treatment with 24
      mmol/L of LiCl, a inhibitor of GSK-3, the OA-induced apoptosis of INS-1 cells was
      lessened and the phosphorylation of GSK-3 was increased remarkably. It is
      concluded that GSK-3 activation plays an important role in OA-induced apoptosis
      in pancreatic beta-cells and inhibition of the GSK-3 activity can effectively
      protect INS-1 cells from the OA-induced apoptosis. Our study provides a new
      experimental basis and target for the clinical treatment of type-2 diabetes.

PMID- 18060616
TI  - Construction of recombinant plasmid harboring APP717 mutation and preliminary
      study of APP proteolysis.
AB  - In order to investigate the pathogenesis of Alzheimer disease (AD) and study the
      enzymatic progress of amyloid precursor protein (APP), the fluorescent eukaryotic
      expression plasmid of C99 was constructed containing APP717 mutation. The
      fragment encoding the last 99-aa of APP (which was named C99 containing APP717
      mutation), together with the fragment encoding yellow fluorescence protein (which
      was named YFP) were amplified by PCR. The two fragments (YFP and C99) were
      inserted into the vector pcDNA3.0. The recombinant plasmid pcDNA3.0-YFP-C99 was
      accomplished and its authenticity was confirmed by enzyme digestion and
      sequencing. Then SH-SY5Y cells were transiently transfected with the recombinant
      plasmid pcDNA3.0-YFP-C99. The expression of the fusion gene was detected by laser
      confocalmicroscopy. Amyloid-beta (Abeta) was detected by both microscopy and
      immunochemistry. The authenticity of the construct was confirmed by the
      endonuclease digestion and DNA sequencing. The YFP fluorescence could be seen and
      proved the expression of fusion gene. Abeta labeled by YFP was detected by
      confocalmicroscopy and confirmed by immunocytochemistry. It was found that Abeta
      accumulated and deposited in the intracytoplasm, membrane and outside of the
      cell. Furthermore, Abeta accumulated mainly within the cell ahead of the
      deposition in the cell space and the cell shape was rough. It was suggested that
      Abeta could be generated within the cells. Abeta accumulated in the cell at the
      early stage before the deposition outside of the cells. Intracellular Abeta
      accumulation induced the secondary damage to the cells and caused the cell shape
      rough. Taken together, the recombinant plasmid, pcDNA3.0-YFP-C99 could be a
      useful tool to further study the cleavage mechanism of APP and to explore the
      pathogenesis of AD.

PMID- 18060617
TI  - Effect of ATRA on contents of liver retinoids, oxidative stress and hepatic
      injury in rat model of extrahepatic cholestasis.
AB  - The effects of all-trans-retinoic acid (ATRA) administration on the concentration
      of retinoids (RA and vitamin A) in liver, oxidative stress and the hepatic injury
      in a rat model of common bile duct ligation (CBDL)-induced liver injury were
      investigated. Female rats were subjected to a sham (n=5) or CBDL (n=48). Two
      weeks after operation, rats undergoing CBDL were randomized to receive treatment
      with either ATRA at three different doses (0.1, 1.5, 7.5 mg/kg) dissolved in bean
      oil or only bean oil every day over a 4-week experimental period. Rats were
      killed and blood samples were collected from the heart for determination of the
      serum transaminase. The contents of retinoids in rat liver were detected by using
      HPLC. Malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)
      levels in liver were determined by a spectrophotometric method according to the
      instruction of the kits. Liver pathologic changes were observed under the light
      microscopy and electron microscopy. The results showed that compared with sham
      operated group, the levels of retinoids in the liver tissue were significantly
      decreased in the CBDL group (P<0.01). ATRA (0.1 mg/kg) administration in CBDL
      rats partially restored the contents of retinoids (P<0.05). Liver RA and vitamin
      A contents in CBDL group were significantly increased after ATRA (1.5 and 7.5
      mg/kg) supplementation as compared with sham-operated group (P<0.05). However, in
      ATRA-treated CBDL group, hepatic GSH level and SOD activity, depressed by CBDL,
      and hepatic MDA level, increased by CBDL were returned to those in sham-operated
      group (P<0.05). The histologic observation of liver tissues indicated that ATRA
      treatment notably alleviated hepatocellular swelling, steatosis, the swelling of
      mitochondria and proliferation of smooth endoplasmic reticulum (SER). Treatment
      with ATRA could reduce levels of serum transaminase as compared with sham
      operated group, more greatly in 1.5 and 7.5 mg/kg ATRA-treated groups than in 0.1
      mg/kg ATRA-treated group. It was concluded that ATRA treatment can recover MDA
      and GSH levels and SOD activity in CBDL rat liver through restoring RA and
      vitamin A contents, and eventually ameliorate liver injury.

PMID- 18060618
TI  - Clinical value of vascular endothelial growth factor combined with interferon
      gamma in diagnosing malignant pleural effusion and tuberculous pleural effusion.
AB  - In order to investigate the clinical value of vascular endothelial growth factor
      (VEGF) combined with interferon-gamma (IFN-gamma) in diagnosing malignant pleural
      effusion and tuberculous pleural effusion, 42 cases of malignant pleural effusion
      and 45 cases of tuberculous pleural effusion in Tongji Hospital, from March 2004
      to May 2005, were included. The carcinoembryonic antigen (CEA), VEGF and IFN
      gamma levels of pleural effusion were detected by using ELISA, and adenosine
      deaminase (ADA) activity was determined by using enzyme kinetic analytical
      method. The sensitivity, specificity, accuracy and area under the curve
      (AUC(ROC)) of CEA and VEGF, VEGF/IFN-gamma ratio, ADA and IFN-gamma were measured
      by receiver operating characteristic curve (ROC). The results showed that CEA,
      VEGF levels and VEGF/IFN-gamma ratio were significantly higher and the ADA and
      IFN-gamma levels were significantly lower in malignant group than those in
      tuberculous group (P<0.01). The sensitivity, specificity, accuracy and AUC(ROC)
      of VEGF/IFN-gamma ratio (88.7%, 99.8%, 94.4%, 0.96 respectively) were higher than
      those of CEA (67.8%, 96.1%, 82.4%, 0.78 respectively) and VEGF (81.5%, 84.3%,
      82.9%, 0.79 respectively). The sensitivity, specificity, accuracy and AUC(ROC) of
      IFN-gamma (85.7%, 96.4%, 90.9%, 0.94 respectively) were higher than those of ADA
      (80.2%, 87.6%, 83.8%, 0.81 respectively). It was concluded that VEGF/IFN-gamma
      ratio and IFN-gamma could be used as valuable parameters for the differential
      diagnosis of malignant pleural effusion and tuberculous pleural effusion.

PMID- 18060619
TI  - Expression of interleukin-17 in lung and peripheral blood of asthmatic rats and
      the influence of dexamethasone.
AB  - The expression of interleukin-17 (IL-17) in lung and peripheral blood of
      asthmatic rats and the influence of dexamethasone, and the role of IL-17 in the
      pathogenesis of asthma were investigated. Thirty Sprague-Dawley (SD) adult rats
      were randomly divided into three groups (n=10 in each group): normal group,
      asthmatic group, and dexamethasone-interfered group. Rat asthmatic model was
      established by intraperitoneal (i.p.) injection of 10% ovalbumin (OVA) and
      challenge with 1% OVA via inhalation. Rats in dexamethasone-interfered group were
      pretreated with dexamethasone (2 mg/kg, i.p.) 30 min before each challenge. The
      expression of IL-17 protein in serum and bronchoalveolar lavage fluid (BALF) was
      detected by ELISA. The expression of IL-17 mRNA in peripheral blood mononuclear
      cells (PBMC) and BALF cells was semi-quantitatively detected by RT-PCR. The
      expression of IL-17 protein in serum and BALF of asthmatic rats was significantly
      elevated as compared with normal rats and dexamethasone-interfered rats (P<0.01),
      and there was significant difference between normal rats and dexamethasone
      interfered rats (P<0.05). The expression of IL-17 mRNA in PBMC and BALF cells of
      asthmatic rats was markedly increased as compared with normal rats and
      dexamethasone-interfered rats (P<0.01), and significant difference was found
      between normal rats and dexamethasone-interfered rats (P<0.05). It was concluded
      that the expression of IL-17 was increased significantly in asthmatic rats and
      could be inhibited partly by dexamethasone, suggesting that IL-17 might play an
      important role in the pathogenesis of asthma as an inflammation regulation
      factor.

PMID- 18060620
TI  - The effect of interleukin-18 on airway inflammation in asthmatic murine models
      and its mechanisms.
AB  - In order to investigate the effect of interleukin-18 (IL-18) on airway
      inflammation in asthmatic murine models and its mechanisms, BALB/C mice were
      randomly divided into three groups (n=10 in each group): group A (control group);
      group B (asthmatic model group); group C (IL-18-treated group). The asthmatic
      model was established in groups B and C by respiratory syncytial virus (RSV)
      killed by ultraviolet. Saline solution (0.1 mL) and IL-18 (0.1 mL, 1 microg) were
      intraperitoneally injected respectively in groups B and C at 7 time points (day
      1, 2, 7, 8, 9, 21, 22). The number of eosinophils (EOS) and plasmacytes in the
      airway was observed. The levels of interferon gamma (IFN-gamma) in
      bronchoalveolar lavage fluid (BALF) were measured by ELISA. The results showed
      that symptoms of asthma in group C were more severe than in groups A and B. In
      group A, there were no EOS and plasmacytes in the airway submucosa. The number of
      EOS [15+/-3 (average cell counts per microscopic visual field, the same below)]
      and plasmacytes (10+/-2) in group B were increased significantly. However, the
      number of EOS and plasmacytes in group C (6+/-2 and 2+/-1, respectively) was
      decreased significantly as compared with group B (both P<0.05). The levels of IFN
      gamma in groups A, B and C were 31+/-3, 40+/-5 and 63+/-5 pg/mL respectively, and
      those in group C were significantly higher than in groups A and B (both P<0.05).
      It was suggested that the mechanism by which IL-18 inhibited the airway
      inflammation in asthmatic mice might be contributed to the fact that IL-18 could
      induce the induction of IFN-gamma.

PMID- 18060621
TI  - Dynamic expression of tumor necrosis factor-alpha and vascular endothelial growth
      factor in rat model of pulmonary emphysema induced by smoke exposure.
AB  - In order to explore the roles of tumor necrosis factor-alpha (TNF-alpha) and
      vascular endothelial growth factor (VEGF) in the pathogenesis of pulmonary
      emphysema, male Wistar rats were randomized into group A(1), group A(2.5) and
      group A(4), each with smoke exposure for 1 month, 2.5 months or 4 months,
      respectively. Group B(1), group B(2.5) and group B(4) were used as non smoking
      controls at corresponding time points. TNF-alpha in bronchoalveolar lavage fluid
      (BALF) and expression of VEGF in lung tissue was determined by ELISA or by SABC
      immunohistochemistry assay either. Lung slices were stained with hematoxylin and
      eosin (HE). Results showed that in animal with smoke exposure the mean linear
      interceptor (Lm), an index of pulmonary emphysema and the content of TNF-alpha in
      BALF increased gradually, on contrary, the expression of VEGF in lung tissue
      decreased (P<0.05). This phenomenon was not obvious in animals without smoke
      exposure. Lm was negatively correlated to the VEGF expression (gamma=-0.81,
      P<0.01) and positively correlated to TNF-alpha concentration (gamma = 0.52,
      P<0.004), which implies that smoke exposure decreased the expression of VEGF and
      increased the expression of TNF-alpha. It is plausible to speculate that the
      imbalance of TNF-alpha and VEGF may play an important role in the pathogenesis of
      smoke-induced pulmonary emphysema.

PMID- 18060622
TI  - Resveratrol inhibits the secretion of vascular endothelial growth factor and
      subsequent proliferation in human leukemia U937 cells.
AB  - This study examined the effect of resveratrol on the secretion of vascular
      endothelial growth factor (VEGF) and subsequent proliferation of human leukemia
      U937 cells, and explored the mechanisms involved. Human leukemia U937 cells were
      treated with resveratrol of different concentrations (12.5-200 micromol/L) for
      different time lengths (12-48 h). The proliferation of the U937 leukemic cells
      was determined by MTT assay. Apoptosis was observed by Annexin-V-FIFC/PI double
      staining and flow cytometry (FCM). Cells cycle was analyzed by PI staining and
      FCM. The content of VEGF was determined by ELISA. Human umbilical vein
      endothelial cells were examined for vasoformation in vitro after exposures to
      resveratrol of various concentrations. The results showed that resveratrol
      inhibited the proliferation of U937 leukemia cells in a dose-and time-dependent
      manner. Resveratrol induced apoptosis and S-phase cell cycle arrest in human
      leukemic U937 cells. Resveratrol inhibited the secretion of VEGF in U937 cells.
      Resveratrol inhibited the vasoformation of human vein endothelial cells in a dose
      dependent manner. It was concluded that resveratrol could down-regulate the
      secretion of VEGF, induce apoptosis and suppress the proliferation of U937 cells.

PMID- 18060623
TI  - Antitumor effect of interferon-alpha on U937 human acute leukemia cells in vitro
      and its molecular mechanism.
AB  - In order to investigate the antitumor effect and molecular mechanism of
      interferon-alpha (IFN-alpha) on human acute myeloid leukemia cell line U937 cells
      in vitro, the proliferation of U937 cells was determined by MTT assay, the
      apoptosis rate was analyzed by flow cytometry (FCM), and the mRNA expression of
      cell cycle regulatory protein cyclin E was detected by RT-PCR. The results showed
      that IFN-alpha could inhibit the proliferation of U937 cells significantly in a
      dose-and time-dependent way (P<0.01), and induce the apoptosis of U937 cells also
      in a dose-and time-dependent manner at the concentration of 1000-4000 U/L
      (P<0.01). The apoptosis rate of U937 cells was even over 50% when cultured with
      IFN-alpha for 36-48 h at the concentration of 2000-4000 U/L. Moreover, the
      expression of cyclin E mRNA was markedly inhibited by the addition of IFN-alpha,
      and the inhibition was time-dependent (P<0.01). It was concluded that the anti
      leukemia mechanism of IFN-alpha might be correlated with its antiproliferative
      and apoptotic inducing effects, and the down-regulation of the cyclin E
      expression might be one of its molecular mechanisms.

PMID- 18060624
TI  - Effect of calcium-channel antagonist on repolarization heterogeneity of
      ventricular myocardium in an in vitro rabbit model of long QT syndrome.
AB  - Intracellular Ca(2+) and Ca(2+)-dependent signaling molecule play an essential
      role in the genesis of long-QT (LQT) syndrome-related ventricular arrhythmias.
      The effect of calcium-channel antagonist verapamil on repolarization
      heterogeneity of ventricular myocardium was assessed in an in vitro rabbit model
      of LQT syndrome. By using the monophasic action potential (MAP) recording
      technique, MAPs of epicardium, mid-myocardium and endocardium were simultaneously
      recorded by specially designed plunge-needle electrodes across the left
      ventricular free wall in rabbit hearts perfused by Langendorff method with
      standard Tyrode's solution. Bradycardia was induced by complete ablation of
      atrioventricular node. A catheter was introduced into the right ventricle to pace
      at the cycle lengths (CLs) of 1500, 1000, and 500 ms, successively. Quinidine (2
      micromol/L) prolonged QT interval and ventricular MAP duration (MAPD), and
      increased transmural dispersion of repolarization (TDR) in a reverse rate
      dependent fashion in isolated rabbit heart. No polymorphic ventricular
      tachycardias were induced under this condition. The effective free therapeutic
      plasma concentrations of verapamil (0.01-0.05 micromol/L) used in this experiment
      had no effect on quinidine-induced changes of QT interval, MAPD and TDR. This
      study demonstrated that, in this model of LQT syndrome, blockade of calcium
      channel with verapamil had no effect on quinidine-induced changes of
      repolatiation heterogeneity of ventricular myocardium.

PMID- 18060625
TI  - Association of G+1688A polymorphism of platelet endothelial cell adhesion
      molecule-1 gene with myocardial infarction in the Chinese Han population.
AB  - In order to investigate the association of G+1688A (Ser563Asn) polymorphism of
      platelet endothelial cell adhesion molecule-1 (PECAM-1) gene with myocardial
      infarction (MI) in the Chinese Han population, the G+1688A polymorphism in PECAM
      1 gene was detected by polymerase chain reaction-restriction fragment-length
      polymorphism (PCR-RFLP) method among 502 subjects, including 218 patients with MI
      and 284 controls. The results showed that there was significant difference in AA
      frequencies of genotype G+1688A polymorphism between case and control groups (39%
      vs 24%, P<0.001). A similar trend was observed on the allele frequencies (A/G:
      62% vs 49%, P<0.001). Among the subjects with high serum total cholesterol level
      or high systolic blood pressure level, the variant AA genotype was associated
      with high risk of MI (adjusted OR, 2.13; 95% CI, 1.08-4.41 and adjusted OR, 2.53;
      95%CI, 1.63-3.63). The single nucleotide polymorphism (SNP) at position +1688 in
      the exon 8 of PECAM-1 gene was associated with MI and the allele A might be a
      risk factor for MI in the Chinese Han population.

PMID- 18060626
TI  - Changes of CD4+CD25+ regulatory T cells in patients with acute coronary syndrome
      and the effects of atorvastatin.
AB  - The function of CD4(+)CD25(+) regulatory T lymphocytes (Treg) in patients with
      acute coronary syndrome (ACS) and the effects of atorvastatin were investigated.
      Forty-eight patients with ACS were randomly divided into two groups: group C
      receiving conventional therapy (n=24), and group C+A receiving conventional
      therapy+atorvastatin (10 mg/day, n=24). T lymphocytes from ACS patients (before
      and 2 weeks after the treatment) or 18 healthy subjects were separated and the
      flow cytometry was used to measure the percentage of Treg. The inhibitory ability
      of Treg on effector T cells was determined by mixed lymphocyte reaction (MLR).
      ELISA was used to measure the serum levels of cytokines (IL-10, TGF-beta1 and IFN
      gamma) before and after treatment. The results showed that as compared with
      normal control group, Treg percentage was decreased significantly (P<0.01), the
      inhibitory ability of Treg on the T lymphocytes proliferation was reduced
      (P<0.01), IFN-gamma levels were increased and IL-10 and TGF-beta1 levels were
      lowered in ACS patients. After treatment with atorvastatin, Treg percentage and
      the inhibitory ability of Treg on T lymphocytes proliferation were significantly
      increased in ACS patients. Serum IFN-gamma was decreased significantly, while IL
      10 and TGF-beta1 were elevated significantly as compared with the non
      atorvastatin group. The number of Treg was positively correlated with serum TGF
      beta1, but negatively with serum IFN-gamma and CRP. It was concluded that ACS was
      associated with decreased number and defected function of Treg, which may play an
      important role in initiating immune-inflammatory response in ACS. The inhibitory
      effects of atorvastatin on inflammation in ACS may be due to its beneficial
      effects on Treg and restoration of immune homeostasis.

PMID- 18060627
TI  - Preventive effects of nitroglycerine on glucocorticoid-induced osteoporosis in
      growing rats.
AB  - The preventive effects of nitroglycerine (NG) on glucocorticoid-induced
      osteoporosis in growing rats were studied. Three-month-old female Wistar rats
      were randomly divided into control group (CON), dexamethasone group (DXM), DXM
      plus a low dose NG group (NG-L), DXM plus a middle dose NG group (NG-M) and DXM
      plus a high dose NG group (NG-H), 8 rats in each group. The rat model of
      osteoporosis was developed by intramuscular injection of dexamethasone twice a
      week. NG 0.2, 0.4 and 1.0 mg/kg was administered by oral gavages to the treatment
      groups every day for 12 weeks. Rats in CON group and DXM group were treated with
      normal saline of the same amount. After the treatment, the bone mineral density
      (BMD) and bone metabolism-associated biochemical markers were determined.
      Compared with CON group, BMD of lumbar spine and femur in DXM group was decreased
      significantly (P<0.05 and P<0.01 respectively), blood BGP levels and NO levels
      reduced (both P<0.01), and TRAP level increased (P<0.05). As compared with DXM
      group, BMD, serum BGP and NO were increased, and TRAP decreased in NG-L group and
      NG-M group, but had no significant difference in comparison to CON group. All the
      markers other than serum NO and TRAP levels had no significant difference between
      NG-H group and DXM group. It was concluded that low or middle doses of NG could
      prevent glucocorticoid-induced bone loss in growing rats, but high dose of NG
      could not. Supplement with NO donor could be considered as a preventive treatment
      for glucocorticoid-induced osteoporosis in a developing skeleton.

PMID- 18060628
TI  - Detection of HBV and HCV coinfection by TEM with Au nanoparticle gene probes.
AB  - Gold(Au) nanoparticle HBV DNA or HCV cDNA gene probes were prepared and were used
      to detect HBV DNA and HCV RNA extracted from positive serum of patients with HBV
      and HCV coinfection directly by transmission electron microscopy (TEM). PCR
      identifying HBV and HCV in serum of patients with HBV and HCV coinfection was
      established. Alkanethiol-modified oligonucleotide was bound with self-made Au
      nanoparticles to form nanoparticle HBV DNA or HCV cDNA gene probes through
      covalent binding of Au-S. HBV DNA and HCV RNA extracted from positive serum of
      patients with HBV and HCV coinfection was added to the detection system composed
      of nanoparticle HBV DNA and(or) HCV cDNA gene probes. The results showed that HBV
      DNA and HCV RNA could be specifically amplified by PCR. The zones of DNA
      amplification appeared in 431 bp and 323 bp respectively. When HBV DNA and HCV
      RNA extracted from positive serum of patients with HBV and HCV coinfection were
      added to the detection system, TEM displayed the nanoparticles self-assembled
      into large network aggregates. It was concluded that the detection of HBV and HCV
      coinfection by TEM was convenient and efficient with high specificity and
      sensitivity.

PMID- 18060629
TI  - Effect of TSLC1 gene on proliferation, invasion and apoptosis of human
      hepatocellular carcinoma cell line HepG2.
AB  - The recombinant plasmid pCI-TSLC1 carrying TSLC1 gene was stably transfected into
      human hepatocellular carcinoma cell line HepG2. Cell proliferation was analyzed
      by MTT assay. The ability of migration was determined by transwell and FACSort
      flow cytometry was used to detect the cell cycle distribution and apoptosis.
      Western blotting revealed that H4 expressed higher amounts of TSLC1 protein than
      H15 and H0 did. The growth of TSLC1-transfected cells was significantly
      suppressed in vitro, and the ability of migration was reduced as well. The re
      expression of TSLC1 could induce cell apoptosis. It was concluded that TSLC1
      strongly inhibited the growth and ability of migration of HepG2 cell line in
      vitro and also induced apoptosis, suggesting that TSLC1 could reduce the
      tumorigenicity of human hepatocellular carcinoma cell line HepG2 in vitro, which
      provided a basis for further exploring the roles of TSLC1 in hepatocellular
      cellular carcinoma.

PMID- 18060630
TI  - Differential gene expression profiles in acute hepatic failure model in mice
      infected with MHV-3 virus intervened by anti-hepatic failure compound.
AB  - Differential gene expression profiles in Balb/cJ mouse model of acute hepatic
      failure infected with MHV-3 virus intervened by anti-hepatic failure compound
      (AHFC) and the changes of cytokines regulated by genes were investigated. The
      Balb/cj mice were divided into AHFC-intervened group and control group randomly.
      Acute hepatic failure model of Balb/cJ mice infected with MHV-3 virus was
      established. The survival rate in the two groups was observed. It was found that
      the survival rate in the AHFC-intervened group and control group was 90% and 50%
      respectively 48 h after intraperitoneal injection of MHV-3 (P<0.05). Before and
      after the experiment, the cytokines in peripheral blood of the survival mice were
      determined, and RNA was extracted from survival mouse liver tissue for the
      analysis of the differential gene expression by a 36 kb mouse oligonucleotide DNA
      array. In all the genes of microarray there were 332 genes expressed differently
      in the two groups, in which 234 genes were up-regulated and 78 genes down
      regulated. Through clustering analysis, the differential expression of immune
      related genes, including TNF receptor superfamily, Kctd9, Bcl-2, Fgl2, IL-8, IL
      6, IFN-gamma, TNF-alpha etc. might be related with the curative effectiveness of
      AHFC. It was suggested that AHFC can balance the immune state of mouse model of
      acute hepatic failure infected with MHV-3 virus mainly through regulating the
      expression of immune related genes, decrease the immune damage and inhibit liver
      cell apoptosis of mouse acute hepatic failure model obviously so as to increase
      the survival rate of mouse models of acute hepatic failure.

PMID- 18060631
TI  - Effects of 5-Aza-CdR on cell proliferation of breast cancer cell line MDA-MB-435S
      and expression of maspin gene.
AB  - The effects of 5-Aza-2'-deoxycytidine (5-Aza-CdR) on the proliferation of MDA-MB
      435S cells and the expression of tumor suppressor gene maspin were investigated.
      Human breast cancer cell line MDA-MB-435S was treated with 5 micromol/L 5-Aza
      CdR, a specific demethylating agent for 0 to 8 days. The growth of MDA-MB-435S
      cells was observed by MTT assay before and after 5-Aza-CdR treatment,
      respectively. The expression of maspin mRNA was detected by reverse transcription
      polymerase chain reaction (RT-PCR). The cell cycle of MDA-MB-435S cells was
      analyzed by flow cytometry. The results showed that the growth of MDA-MB-435S
      cells treated with 5-Aza-CdR for 8 days was significantly suppressed as compared
      with the control groups, and the inhibition rate increased sharply from 5 day to
      8 day (35.42% to 71.29%). Flow cytometry showed that 5 micromol/L 5-Aza-CdR could
      induce G(2)/M cell cycle arrest and decrease the percentage of mitosis cell
      number in this cell line. Maspin mRNA was expressed in MDA-MB-435S cells after 5
      Aza-CdR treatment, but it was weakly detectable before the treatment. It was
      concluded that Maspin gene might be transcriptional silencing by hypermethylation
      and the re-expression of maspin gene by 5-Aza-CdR can inhibit the proliferation
      and induce the G2/M arrest of MDA-MB-435S breast cancer cells.

PMID- 18060632
TI  - Modulatory effects of EPA and DHA on proliferation and apoptosis of pancreatic
      cancer cells.
AB  - In order to investigate the effects of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) on the proliferation, apoptosis of pancreatic cancer
      cell line SW1990 cells and the expression of cyclin E mRNA, the SW1990 cells were
      treated with different concentrations of EPA or DHA (20, 40, 60 microg/mL) for 0,
      12, 24, 36 and 48 h respectively. By using MTT method, the inhibitory effects of
      EPA or DHA on the cell growth were assayed. Real time PCR was used to detect the
      expression changes of cyclin E mRNA after the SW1990 cells were treated with 40
      microg/mL EPA or DHA for different time. Flow cytometry was used to test the
      changes of apoptostic rate in the SW1990 cells treated with different
      concentrations of EPA or DHA for 24 h. The results showed that EPA and DHA could
      inhibit the growth of SW1990 cells in a time-and concentration-dependent manner
      (P<0.01). EPA or DHA could also significantly inhibit the expression of cyclin E
      mRNA in a time-dependent manner (P<0.05). EPA or DHA could induce the apoptosis
      of SW1990 cells in a concentration-dependent manner (P<0.01). It was concluded
      that omega-3 fatty acid could inhibit the proliferation of pancreatic cancer cell
      line SW1990 cells and promote their apoptosis. The down-regulation of the cyclin
      E expression by omega-3 fatty acid might be one of the mechanisms for its anti
      tumor effect on pancreatic cancer.

PMID- 18060633
TI  - Effect of anti-KDR antibody on the proliferation of hemangioma vascular
      endothelial cells in vitro.
AB  - The suppressive effect of anti-KDR antibody against VEGF on proliferation of
      hemangioma-derived vascular endothelial cells (HVECs) was investigated. HVECs
      from one case of hemangioma in proliferative phase were cultured. Both primary
      culture and sub-culture were conducted in M199 medium. The HVECs of passage 3
      were divided into 4 groups based on the concentrations of anti-KDR antibody. Cell
      count was performed and inhibitory rate of HVECs was measured before and 9 days
      after interference. The results showed that the number of HVECs in the anti-KDR
      antibody-treated groups was significantly decreased and the inhibitory rate of
      HVECs by anti-KDR antibody (50, 10 and 2 microg/mL) was 84%, 63% and 39%
      respectively at 9th day after interference, with the difference being
      significant. In the control group, the number of HVECs was increased
      significantly. In was concluded that the anti-KDR antibody could suppress the
      activity of VEGF through blocking the KDR, indicating the potential clinical
      applications of anti-KDR antibody in the treatment of hemangioma.

PMID- 18060634
TI  - Preparation and preservation of hypoxia UW solution.
AB  - In order to explore the method to prepare hypoxia UW solution and the stability
      and preservation of hypoxia UW solution, UW solution was purged by argon or air
      for 15 min or 60 at a flow rate of 0.8 or 2 L/min, and the oxygen partial
      pressure of UW solution was detected. The hypoxia UW solution was exposed to the
      air or sealed up to preserve by using different methods, and the changes of
      oxygen partial pressure was tested. The results showed that oxygen partial
      presure of 50 mL UW solution, purged by argon for 15 min at a flow rate of 2
      L/min, was declined from 242+/-6 mmHg to 83+/-10 mmHg. After exposure to the air,
      oxygen partial pressure of hypoxia UW solution was gradually increased to 160+/-7
      mmHg at 48 h. After sealed up by the centrifuge tube and plastic bad filled with
      argon, oxygen partial pressure of hypoxia UW solution was stable, about 88+/-13
      mmHg at 72 h. It was concluded that oxygen of UW solution could be purged by
      argon efficiently. Sealed up by the centrifuge tube and plastic bag filled with
      argon, oxygen partial pressure of UW solution could be stabilized.

PMID- 18060635
TI  - Effect of Stathmin decoy-oligodeoxynucleotides on the proliferation and
      differentiation of precartilainous stem cells.
AB  - By using decoy-oligodeoxynucleotides (decoy-ODNS) technique, the effects of
      Stathmin gene on the proliferation and differentiation of in vitro cultured
      precartilainous stem cells (PSCs) were investigated. The Stathmin decoy-ODNs were
      transfected into PSCs in rats by using gene transfection technique. Under the
      induction of cortisol (1 micromol/L), electrophoretic mobility shift assay was
      used the inhibitory effects of decoy-ODNS on Stathmin gene. MTT and cytometry
      were used to test the cell proliferation. The expression of collagen II and V and
      Stathmin protein was detected by using Western blot. The results showed that
      Stathmin decoy-ODNs inhibited the Stathmin activity in a dose-dependent manner.
      When the concentration of decoy-ODNs was 10 times of standard concentration, the
      proliferation of PSCs was obviously suppressed and the differentiation happened.
      Compared to the control group, the difference was significant (P<0.05). It was
      concluded that decoy-ODNs could inhibit the proliferation and promote the
      differentiation of PSCs by antagonizing Stathmin activity.

PMID- 18060636
TI  - Effect of rhBMP-2 and osteogenic revulsants on proliferation and differentiation
      of bone marrow stromal cells in rats.
AB  - The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) and
      osteogenic revulsants alone or in combination at different time points and in
      different dosages on proliferation and osteogenesis of bone marrow stromal cells
      (BMSCs) in SD rats were investigated. Rat BMSCs were cultured in vitro and
      induced by rhBMP-2 in different dosages (10, 50, 100 and 200 mug/L) alone or in
      combination with osteogenic revulsants. MTT colorimetric assay was used to
      evaluate The proliferation, activity of alkaline phosphoric (ALP) and osteocalcin
      were measured at 3rd, 6th, 9th, 12th day respectively. The results showed that
      rhBMP-2 and osteogenic revulsants could promote the differentiation of BMSCs
      towards osteoblast phenotype. The proliferation of BMSCs could be enhanced by
      rhBMP-2 in a dose-dependent manner. The expression of osteoblast phenotype was
      significantly higher by using both of them than by using them alone, which was
      verified by the activity of ALP and osteocalcin. It was suggested that the
      combined use of rhBMP-2 and osteogenic revulsants could promote the proliferation
      and simultaneously induce and maintain the expression of osteoblast phenotype of
      BMSCs in rats.

PMID- 18060637
TI  - Gene expression profile of pulmonary tissues in different phases of lung ischemia
      reperfusion injury in rats.
AB  - In order to provide us new clues to induce some endogenous protective molecular
      mechanisms, the changes in gene expression profile induced by ischemia
      reperfusion in pulmonary tissues of rats were investigated and the dynamic
      mechanism of pulmonary ischemia-reperfusion injury was elucidated. Thirty male
      Wistar rats were randomly divided into 6 groups: 5 ischemia-reperfusion (I/R)
      groups (I/R 0-h, I/R 1-h, I/R 3-h, I/R 6-h, I/R 24-h) and control group (n=5 in
      each). An in situ ischemia-reperfusion lung injury rat model was established by
      occluded hilus of lung. The RatRef-12 Expression Beadchip (22 226 gene probes per
      array) was used to analyze the pattern of gene expression in all groups. The
      results showed that 648, 340, 711, 1279 and 641 genes were differentially
      expressed in I/R 0-, 1-, 3-, 6-and 24-h groups respectively. The differentially
      expressed genes were classified as following 7 functional categories: cytokine,
      adhesion molecule, growth factor and apoptosis-related factor, oxidation and
      antioxidation molecule, metabolic enzyme, ion channel and aquaporin, signal
      transduction molecule. It was suggested that gene chip technology was an
      effective and quick method for screening differentially expressed genes. Many
      differentially expressed genes with different functions interacted each other to
      result in pulmonary ischemia-reperfusion injury.

PMID- 18060638
TI  - Experimental study on treatment of glioma by embryonic neural stem cell
      transplantation in rats.
AB  - The neural stem cells in Wistar rats were cultured in vitro, purified, and
      transplanted into C6 glioma model in order to observe their biological characters
      and provide a basic foundation for treatment of neurological diseases by neural
      stem cell transplantation. The cells at hippocampal area from gestation 15-day
      rats were cultured in vitro, and frozen and preserved in liquid nitrogen. C6
      tumor-bearing models (n=25) and neural stem cells transplantation models (n=35)
      were established. When the tumor grew to 3 to 4 weeks, 5 rats in each group were
      randomly selected for MRI examination. At different intervals, the rats were
      perfused and sampled for HE staining, GFAP and BrdU immunohistochemical staining.
      The results showed that after resuscitation of neural stem cells at 1-4 passages,
      the cell viability was 40%-63% with the difference being not significant. The
      cells could proliferate, passage, and most cells transplanted into glioma model
      survived. The mean survival time in neural stem cell transplantation group and
      control was 4.28 and 3.88 weeks respectively, and the average tumor size in the
      former was smaller than in the latter. It was concluded that embryonic neural
      stem cells in rats could proliferate and differentiate, and after resuscitation
      the biological characteristic and viability of the cells were not influenced.
      Neural stem cells had inhibitory effects on the growth of glioma cells and could
      prolong the survival of rat model.

PMID- 18060639
TI  - The expression levels of endogenous aFGF mRNA in microwave burn wound tissues and
      its clinical significance.
AB  - The expression levels and changes of endogenous acid fibroblast growth factor
      (aFGF) in microwave burn wound tissues were detected in order to investigate how
      to get better therapeutic effects by using the exogenous aFGF for repairing
      trauma. A burnt-wound animal model was established by NS-F II multifunction
      spectrum therapeutics equipment, and reverse transcriptase-polymerase chain
      reaction (RT-PCR) and immunohistochemistry assay were applied to detect the
      expression levels of endogenous aFGF mRNA in microwave burn wound tissues. The
      expression level of endogenous aFGF mRNA was significantly increased in the burn
      wound tissues 12 h after burn, reached the peak at 48 h, and gradually deceased
      96 h after burn. The expression of endogenous aFGF mRNA after tissue damage was
      reversible, and its intensity was in accordance with the repair process of tissue
      damage, suggesting endogenous aFGF may take part in the cell metabolism and
      proliferation, and then promote the repair of the burn wound.

PMID- 18060640
TI  - Effects of placental isoferritin on the mouse embryo development in vitro.
AB  - To investigate the effect of placental isoferritin (PLF) on mouse embryo
      development in vitro, mice 2-cell embryos were co-cultured with human first
      trimester decidual cells at different concentrations of PLF in vitro. The
      following changes of the above system were observed under an invert microscope
      and the number of embryos were recorded and the embryos were classified. The
      results showed there was no significant difference in the percentage of embryos
      development to 4-cell, 8-cell and morula (P>0.05). PLF at the doses of 10 and 100
      U/mL significantly enhanced more embryos development to the blastocyst and
      hatching blastocyst (P<0.05). PLF at the dose of 1000 U/mL depressed more embryos
      development from 2-cell to hatching blastocyst, meanwhile such phenomena as cell
      degeneration and irregular cleavage were observed in part of embryos, but there
      was no significant difference in statistics (P>0.05). It was concluded that PLF
      at the concentration of 10-100 U/mL had no significant effects on the early
      development of mice embryos, however, PLF could promote the growth,
      differentiation, and hatching of preimplantation blastocysts.

PMID- 18060641
TI  - Screening of differently expressed genes in human prostate cancer cell lines with
      different metastasis potentials.
AB  - In order to screen the genes differentially expressed in two human prostate
      cancer cells with different metastasis potentials, suppression subtractive
      hybridization (SSH) was done twice on human prostate cancer cell line with high
      potential of metastasis PC3M-1E8 and its synogenetic cell line PC3M-2B4 with low
      metastasis potential. In the first subtraction PC3M-2B4 was used as tester and
      PC3M-1E8 as driver and the forward subtractive library was constructed. In the
      second on the tester and driver were interchanged and the reverse subtractive
      library was constructed. The screened clones of both libraries were sequenced and
      Gene Bank homology search was performed. Some clones were confirmed by
      quantitative real-time PCR. The results showed that two subtractive libraries
      containing 238 positive clones were constructed. Analysis of 16 sequenced clones
      randomly picked from two libraries showed that 4 differentially expressed gene
      fragments were identified as new EST with unknown functions. It was concluded
      that two subtractive libraries of human prostate cancer cell lines with different
      metastasis potentials were constructed successfully.

PMID- 18060642
TI  - Inhibitory effect of HCPT on expression of HIF-1alpha and downstream genes in
      hypoxic human cervical SiHa cancer cells.
AB  - The hypoxic model to simulate hypoxic microenvironment in solid tumors was
      established and the effect of hydrocamptothecin (HCPT) on the hypoxia-induced
      over-expression of HIF-1alpha and VEGF genes was explored. Human cervical cancer
      SiHa cells were cultured in vitro under hypoxic conditions (37 degrees C, 5%
      CO(2), 1% O(2)) and treated with different concentrations of HCPT for 24 h. The
      mRNA and protein expression levels of HIF-1alpha, VEGF and Glut1 in SiHa cells
      were detected by semi-quantitative RT-PCR and Western blot respectively. Normoxic
      control groups were exposed to normoxic conditions for 24 h. Under normoxic
      conditions, HCPT had no obvious effects on the HIF-1alpha and VEGF gene
      expression. Hypoxia induced the up-regulation of HIF-1alpha protein and
      downstream VEGF gene, and HCPT showed a dose-dependently inhibitory effect on the
      hypoxia-induced over-expression of HIF-1alpha protein and VEGF gene expression in
      SiHa cells, whereas HCPT had no significant effect on the HIF-1alpha mRNA
      expression. No difference in HCPT cytotoxicity was observed between hypoxic
      groups and normoxic control groups. It was suggested that HCPT could inhibit the
      expression of HIF-1alpha protein and downstream VEGF gene in hypoxic SiHa cells
      in a dose-dependent manner, and the inhibitory effect was not related with HCPT
      cytotoxicity.

PMID- 18060643
TI  - Effect of trace elements on retinopathy of prematurity.
AB  - The effect of the trace elements on retinopathy of prematurity (ROP) were
      studied. Thirty preterm infants who had potential high risk factors of ROP were
      selected as observation group and 18 normal infants as control groups. By using
      atom spectrophotometer, the contents of serum trace elements (Mg, Cu, Zn, Mn, Se)
      were measured and analyzed statistically. The contents of serum Zn, Cu and Se in
      observation group were 0.75+/-0.22, 0.41+/-0.20 and (134.07+/-71.57)x10(-3) mg/L
      respectively, and 0.55+/-0.12, 0.65+/-0.194 and (202.92+/-44.71)x10(-3) mg/L in
      control group respectively (P<0.01). The contents of Cu and Se were obviously
      lower and that of Zn higher in observation group than those in control group. The
      same results were obtained between the infants with ROP and controls (P<0.01).
      However, there was no significant difference in the contents of serum Mg and Mn
      between two groups (P>0.05). It was concluded that the contents of serum Cu and
      Se in preterm infants who had high risk factors of ROP were obviously lower than
      in the controls. The contents of serum Cu and Se in the ROP infants were also
      much lower while contents of Zn much higher. Attention should be paid to the
      detection of the trace elements in preterm infants in order to prevent the
      deficiencies of Cu and Se. Only in this way can we prevent the deficiencies of Cu
      and Se, so as to decrease the ROP risk factors and prevent the disease.

PMID- 18060644
TI  - Diagnosis and treatment of lacrimal passage obstruction by lacrimal endoscope.
AB  - The diagnosis and treatment of the lacrimal passage obstruction with lacrimal
      endoscope was investigated and its subsidiary surgical procedures were evaluated.
      Ninety-three patients (109 eyes) with lacrimal passage obstruction, including
      presaccal canalicular obstruction (PSCO) and nasolacrimal duct obstruction
      (NLDO), were examined under a lacrimal endoscope, and the obstructions were
      treated with laser or micro-drill. All patients were followed up after the
      operation for 3-6 months. The difference between the laser and the micro-drill
      treatment was observed. During the period of follow-up, the curative rate was
      82.57%. The healing rate in PSCO group and NLDO was 80.36% and 84.91%
      respectively (P>0.05). After treatment with the laser, the healing rate was
      93.33% in the PSCO group and 66.67% in the NLDO group respectively (P<0.05).
      After treatment with the micro-drill, the healing rate in PSCO and NLDO groups
      was 65.39% and 94.28% respectively (P<0.01). The lacrimal passage obstruction can
      be observed and treated directly through the lacrimal endoscope. Choosing
      different surgical procedures in operation according to the locations of the
      obstruction is helpful to improve the effectiveness.

PMID- 18060645
TI  - In vitro culture of bone marrow mesenchymal stem cells in rats and
      differentiation into retinal neural-like cells.
AB  - In order to study the in vitro culture and expansion of bone marrow mesenchymal
      stem cells in rats (rMSCs) and the possibility of rMSCs differentiation into
      retinal neural cells, the bone marrow-derived cells in SD rats were isolated and
      cultured in vitro. The retinal neural cells in SD rats were cultured and the
      supernatants were collected to prepare conditioned medium. The cultured rMSCs
      were induced to differentiate by two steps. Immunofluorescence method and anti
      nestin, anti-NeuN, anti-GFAP and anti-Thy1.1 antibodies were used to identify the
      cells derived from the rMSCs. The results showed that the in vitro cultured rMSCs
      grew well and expanded quickly. After induction with two conditioned media, rMSCs
      was induced to differentiate into neural progenitor cells, then into retinal
      neural-like cells which were positive for nestin, NeuN, GFAP and Thy1.1 detected
      by fluorescence method. The findings suggested that rMSCs could be culture and
      expanded in vitro, and induced to differentiate into retinal neural-like cells.

PMID- 18060646
TI  - Influence of high level TGF-beta1 on scleral thickness.
AB  - In order to explore the role of TGF-beta1 in scleral remodeling and the possible
      mechanism, the influence of high level TGF-beta1 on scleral thickness and the
      expression of MMP-2 and TIMP-2 was investigated in a TGF-beta1 transgenic mouse
      model. Alb/TGF-beta1 (Cys(223,225)Ser) TGF-beta1 transgenic mice were used as
      experimental subjects and non-transgenic littermates as controls. Plasma levels
      of TGF-beta1 were determined by ELISA. TGF-beta1, MMP-2 and TIMP-2 levels in
      sclera were detected by using Western blot. The thickness of posterior sclera was
      measured by computerized image analysis of a midsagittal section. Mean difference
      was analyzed with independent t-test. The results showed plasma levels of TGF
      beta1 in transgenic mice were 1.68 times as much as that in the controls
      (P<0.01). TGF-beta1 levels in the sclera of transgenic mice were 2.68 times of
      the controls (P<0.01). Posterior scleral thickness in transgenic mice were
      significantly thicker than in the controls. There was no significant difference
      in the MMP-2 levels between transgenic mice and controls, but the TIMP-2 levels
      were increased significantly in transgenic mice as compared with those in the
      controls. It was suggested that high levels of TGF-beta1 in transgenic mice could
      result in the increased scleral thickness by inducing the expression of TIMP-2 to
      suppress the activity of MMP-2, finally inhibiting the degradation of collagen.

PMID- 18060647
TI  - The expression of interleukin-22 and S100A7, A8, A9 mRNA in patients with
      psoriasis vulgaris.
AB  - In order to study the expression of interleukin-22 (IL-22) and S100A7, A8, A9
      mRNA in the skin lesions of patients with psoriasis vulgaris and their
      relationship, the biopsies were taken from skin lesions in 35 patients with
      psoriasis vulgaris and the skin of 16 normal controls, and the expression levels
      of IL-22 and S100A7, A8 and A9 mRNA were detected by semi-quantitative RT-PCR.
      The results showed that (1) IL-22 and S100A8, A9 mRNA were positively expressed
      in the psoriatic skin lesions but negatively expressed in the normal controls;
      The expression level of S100A7 was (1.133+/-0.040) in the psoriatic skin lesions,
      significantly higher than that in the normal controls (0.744+/-0.037, P<0.01).
      (2) There were significantly positive correlations between the expression of IL
      22/S100A7 mRNA, IL-22/S100A8 mRNA, IL-22/S100A9 mRNA in the psoriasis vulgaris
      (r(1)=0.543, r (2)=0.774, r(3)=0.621, P<0.01). It was concluded that IL-22 and
      S100A7, A8, A9 might play important roles in the occurrence and progression of
      psoriasis.

PMID- 18060648
TI  - In vitro recombination and identification of mutated fragment corresponding to
      regulation region of mtrR gene of Neisseria gonorrhoeae.
AB  - A site-directed mutant DNA fragment was synthesized and transfected into clinical
      Neisseria gonorrhoeae (NG) stains to construct the transformants that contained
      the corresponding mutagenesis of regulation region of mtrR gene. According to the
      technique of gene splicing by overlap extension (SOEing), a DNA segment with
      specific mutagenesis was constructed by two-step polymerase chain reaction (PCR).
      The mutation fragments EF could be used for the next experiment in which the
      mutation NG strains were induced. By comparing the recombinant EF fragments to
      the corresponding DNA fragments of clinical NG strains, 2 of these were not
      compatible completely. The results of sequencing revealed that there was a 9 bp
      deletion between the 45 to 54 inverted repeat sequence localized within the mtrR
      promoter. It can be confirmed that the fragments EF are the specifically designed
      mutant fragments.

PMID- 18060649
TI  - The expression of endothelin receptor B in melanoma cells A375 and Sk-mel-1 and
      the proliferative effects of endothelin 3 on A375 cells.
AB  - In order to investigate the expression of endothelin receptor B (ETR-B) in human
      malignant melanoma (MM) cells A375 and SK-mel-1 and the proliferative effects of
      endothelin 3 (ET3) on A375 cells, RT-PCR was applied to detect the expression of
      ETR-B gene in human MM cells A375 and SK-mel-1. MTT method was used to evaluate
      the growth enhancing effects of ET3 on A375 cell line in vitro. The results
      showed that ETR-B gene was expressed in both MM A375 and SK-mel-1 cells. ET3 had
      stronger ability to enhance the proliferation of A375 cells in vitro in a
      concentration-dependent manner. It was suggested that ET3/ETR-B might play an
      important proliferative role in MM.

PMID- 18060650
TI  - The effect of nitrous oxide and isoflurane on the total RNA yield from the
      cochlea of the rats.
AB  - The possible mechanism of inhalation anesthetics on the internal auditory
      impairment of the rat was investigated by determining the effect of nitrous oxide
      (N(2)O) and isoflurane on the total RNA yield from the cochlea of the rats.
      Thirty healthy Wistar rats were randomly divided into 3 groups: group C (control
      group, n=10) with a 3-h unremitting inhalation of 50% O(2), group N (experiment
      group, n=10) with a continuous inhalation of 50% N(2)O+50% O(2) for 3 h, and
      group I (experiment group, n=10) with a 3-h sustained inhalation of 2.5%
      isoflurane. The TRIzol in combination with RNeasy was used to respectively
      extract the total RNA from cochlea of rats in the 3 groups. Spectrophotometry was
      used to detect total RNA yield and electrophoresis to detect the quality. The
      total RNA extracted from the cochlea of the rats in the groups C and N was 7.69
      and 6.51 microg, respectively. There was a 15% decrease in the N group as
      compared with group C. The total RNA from the rats in the group I was 7.32
      microg, and there was hardly any change in the group as compared with the group
      C. The value of A(260)/A(280) in groups C, N and I was 2.07, 2.04 and 2.04,
      respectively, showing a very high RNA purity. The result of gel electrophoresis
      suggested that there was no degradation in the total RNA. It was suggested that
      the interference of N(2)O on the cochlear RNA yield might be one of the reasons
      which cause an injury of the ear. The isoflurane shows no harm on the hearing.

PMID- 18060652
TI  - The etiology and outcome analysis of neonatal burst suppression EEG.
AB  - The neonatal burst suppression is a severe EEG pattern and always demonstrates
      serious damage of nerve system. But the outcome of these patients depends on the
      different etiology. A total of 256 cases of video EEG recordings were analyzed in
      order to summarize the etiology and outcome of burst suppression. The results
      showed that some patients in all 17 cases of burst suppression showed EEG
      improvement. The etiology was the dominant factor in long term outcome. It was
      suggested that effective video EEG monitoring is helpful for etiologic study and
      prognosis evaluation.

PMID- 18060651
TI  - Age-related marrow conversion and developing epiphysis in the proximal femur:
      evaluation with STIR MR imaging.
AB  - In order to observe the feature of age-related marrow conversion and maturation
      of epiphyseal cartilage and analyze the distribution of red and yellow marrow in
      the proximal femur at STIR MR imaging, STIR and T(1) weighted MR imaging of the
      proximal femur in 52 subjects, aged 4 months to 25 years old, were
      retrospectively analyzed for the distribution and appearance of red and yellow
      marrow. The subjects with no known bone marrow abnormalities were divided into 6
      age groups. The signal intensity of the marrow in the proximal epiphysis,
      proximal metaphysis, proximal diaphysis, distal diaphysis and greater trochanter
      was compared with the signal intensity and homogeneity of surrounding muscle and
      fat and graded by two observers. The results showed that the conversion of
      hematopoietic marrow in the proximal femur followed a well-defined sequence,
      occurring first in the proximal epiphysis, followed by the distal diaphysis, and
      then greater trochanter and metaphysis. STIR in combination with T(1)-weighted
      imaging could display clearly the origin of ossification center and the course of
      conversion from red to yellow marrow in proximal epiphysis and greater
      trochanter. STIR imaging showed that the marrow conversion in proximal metaphysic
      began below epiphyseal plate and intertrochanter. The site of red yellow was
      distributed in weight-bearing axis by 20 years of age. The marrow conversion of
      diaphysis was from distal end to proximal end, and the consequence of conversion
      was that distal diaphysis contained yellow marrow but proximal diaphysis partly
      red marrow connected with the red marrow of metaphysic. The epiphyseal cartilage
      had different characters of signal-intensity with age in STIR sequence. The
      distribution of red marrow in STIR imaging was more close to that of anatomy than
      T(1)-weighted imaging. It was concluded that STIR could dynamically display the
      feature of marrow conversion and the development of epiphyseal cartilage and
      accurately reveal the age-related distribution of red and yellow marrow on STIR
      imaging in the proximal femur.

PMID- 18060653
TI  - [Unusual cause of pneumomediastinum].
AB  - The 3,4-methylenedioxy-N-methylamphetamine (MDMA) also known as ecstasy is a
      hallucinogen prevalently used by teenagers. Known complications of its
      consumption are hyperpyrexia, disseminated intravasal coagulation, acute kidney
      failure, and rhabdomyolysis. We report about an 18-year-old patient who developed
      a pneumomediastinum and skin emphysema by excluded lesions of the lung and
      respiratory tract. We present the hypothesis of the pathogenesis of this disease.
      The correct therapy is observation of the patient and maximum sedation.

PMID- 18060654
TI  - Parasites and health affect multiple sexual signals in male common wall lizards,
      Podarcis muralis.
AB  - Multiple advertising sexual traits may either advertise different characteristics
      of male condition or be redundant to reinforce reliability of signals. Research
      has focused on multiple visual traits. However, in animals that use different
      multiple additional sensory systems, such as chemoreception, different types of
      traits might have evolved to signal similar characteristics of a male quality
      using different sensory channels. We examined whether ventral coloration and
      chemicals in femoral gland secretions of male common wall lizards, Podarcis
      muralis, are affected by their health state (blood-parasite load and cell
      mediated immune response). Our results indicated that less parasitized lizards
      had brighter and more yellowish ventral colorations and also femoral secretions
      with higher proportions of two esters of octadecenoic acid. In addition, lizards
      with a greater immune response had more saturated coloration and secretions with
      higher proportions of octadecenoic acid methyl ester. We suggest that these
      signals would be reliable because only healthier males seemed able to allocate
      more carotenoids to coloration and presumably costly chemicals to secretions. The
      use of multiple sensory channels may provide more opportunities to signal a male
      quality under different circumstances, but also may reinforce the reliability of
      the signal when both types of traits may be perceived simultaneously.

PMID- 18060656
TI  - [Safety aspects in high-field magnetic resonance imaging].
AB  - With more and more 3 Tesla high-field magnetic resonance (MR) scanners entering
      clinical routine, the safety notion in MR imaging has also reached a new
      dimension. The first part of this paper deals with the three most important
      sources of physical interaction (static magnetic field, gradient and HF fields).
      The paper discusses the differences compared with the traditional clinical 1.5 T
      standard scanners, the impact on human beings, the interactions with metallic
      objects and the relevant safety standards. The second part of the paper examines
      the issue of MR safety as seen in clinical practice and tries to demonstrate
      optimization potentials. This includes structural optimization in information
      distribution and hospital organization as well as test standards and labeling
      guidelines.

PMID- 18060657
TI  - Distribution and mapping of an active autonomous aDart element responsible for
      mobilizing nonautonomous nDart1 transposons in cultivated rice varieties.
AB  - An endogenous 0.6-kb rice DNA transposon, nDart1, has been identified as a
      causative element of a spontaneous mutable virescent allele pyl-v conferring pale
      yellow leaves with dark-green sectors in the seedlings, due to somatic excision
      of nDart1 integrated into the OsClpP5 gene encoding the nuclear-coded chloroplast
      protease. As the transposition of nDart1 depends on the presence of an active
      autonomous aDart element in the genome, the plants exhibiting the leaf
      variegation carry the active aDart element. As several mutable alleles caused by
      nDart1 insertions have subsequently been identified, nDart1-promoted gene tagging
      has been proven to be an effective system. At present, the nDart/aDart system
      appears to be the only endogenous rice DNA transposon system whose transposition
      activity can be controlled under natural growth conditions without any artificial
      treatments, including tissue cultures. To apply the nDart/aDart tagging system in
      various cultivated rice varieties, we explored the presence and distribution of
      an active autonomous aDart element in 19 temperate japonica, 30 tropical
      japonica, and 51 indica varieties. Only eight temperate japonica varieties were
      found to bear a single copy of an active aDart element, and no aDart activity
      could be detected in the indica varieties examined. Six of seven japonica
      varieties appear to carry the active aDart element at the identical site on
      chromosome 6, whereas the remaining one contains aDart on chromosome 5. Leaf
      variegations in the plants with the mutable pyl-v allele and the excision
      frequencies of endogenous nDart1 elements indicated that the aDart element on
      chromosome 6 is more active than that on chromosome 5. The findings described
      here are an important step in the development of a new and efficient nDart1
      promoted gene-tagging system in various rice cultivars.

PMID- 18060658
TI  - Predictors of cognitive impairment and dementia in older people with diabetes.
AB  - AIMS/HYPOTHESIS: Diabetes is associated with an increased risk of dementia but
      the reasons for this association are unclear because there are many potential
      mechanisms. We explored the relative contribution of diabetes-related variables
      as predictors of dementia in older individuals with diabetes. METHODS: Survivors,
      aged > or =70 or more, were recruited from an existing observational cohort study
      7.6 +/- 1.0 years after baseline, when they underwent a comprehensive assessment
      of diabetes, complications and cardiovascular risk factors. Dementia, probable
      Alzheimer's disease and cognitive impairment without dementia were diagnosed
      clinically. Logistic regression modelling determined independent predictors of
      cognitive diagnoses. RESULTS: Of 302 participants, aged 75.7 +/- 4.6 years, 28
      (9.3%) had dementia (16 with probable Alzheimer's disease) and 60 (19.9%) had
      cognitive impairment without dementia. The major independent longitudinal
      predictors of dementia were older age (per decade; odds ratio 4.0, 95% CI 1.59
      10.10), diabetes duration (for each 5 years; odds ratio 1.69, 95% CI 1.24-2.32),
      peripheral arterial disease (odds ratio 5.35, 95% CI 2.08-13.72) and exercise
      (which was protective; odds ratio 0.26, 95% CI 0.09-0.73). For Alzheimer's
      disease, diabetes duration was an independent predictor in addition to age and
      diastolic blood pressure. The results of the cross-sectional analyses were
      similar with respect to diabetes duration and peripheral arterial disease.
      CONCLUSIONS/INTERPRETATION: Peripheral arterial disease is a strong independent
      risk factor for dementia in diabetes. After adjustment for a wide range of
      potential risk factors, diabetes duration remains independently associated with
      dementia and probable Alzheimer's disease, indicating that factors not measured
      in this study may be important in the pathogenesis of dementia in diabetes.

PMID- 18060659
TI  - Determinants of progression from impaired fasting glucose and impaired glucose
      tolerance to diabetes in a high-risk screened population: 3 year follow-up in the
      ADDITION study, Denmark.
AB  - AIMS/HYPOTHESIS: We sought to identify determinants of progression from impaired
      fasting glucose (IFG) and impaired glucose tolerance (IGT) to diabetes in high
      risk screened individuals. METHODS: In general practices in Denmark, stepwise
      screening for type 2 diabetes mellitus in persons aged 40 to 69 years included a
      risk questionnaire, random blood glucose, HbA1c, fasting blood glucose and an
      OGTT. The 1,821 individuals with IGT or isolated IFG (WHO 1999) were re-invited
      after 1 and 3 years. Follow-up data on glucose measurements were available in
      1,510 individuals and additional clinical data in 1,002 collected at the 3-year
      visits. Regression models using interval censoring were used. RESULTS:
      Progression rates from IFG and IGT to diabetes over 3.5 years were 11.8 and 17.0
      per 100 person-years, respectively and were particularly high in the first year.
      Baseline determinants of progression were: IFG: glucose measures, BMI [per kg/m2,
      rate ratio (RR) 1.04 (95% CI, 1.01-1.08)] and triacylglycerol [per twofold
      increase, RR 2.19 (1.49-3.22)]; and IGT: glucose measures and known hypertension
      [RR 1.46 (1.11-1.93)]. Weight reduction and decreased triacylglycerol were
      inversely associated with development of diabetes in IFG individuals [per 1
      kg/year, RR 0.81 (0.66-0.98) and per 1 mmol l(-1) year(-1), RR 0.08 (0.01-0.51),
      respectively], whereas in IGT participants only weight reduction was inversely
      associated [per 1 kg/year, RR 0.80 (0.67-0.96)]. CONCLUSIONS/INTERPRETATION:
      Higher levels of glucose measures, larger BMI, known hypertension and
      hypertriacylglycerolaemia are significant determinants of progression in high
      risk screened individuals. Weight loss of 1 kg/year or reduction of
      hypertriacylglycerolaemia markedly reduced the risk of diabetes.

PMID- 18060660
TI  - Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention
      Program.
AB  - AIMS/HYPOTHESIS: Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic
      atrophy and deafness) is caused by mutations in the WFS1 gene. Recently, single
      nucleotide polymorphisms (SNPs) in WFS1 have been reproducibly associated with
      type 2 diabetes. We therefore examined the effects of these variants on diabetes
      incidence and response to interventions in the Diabetes Prevention Program (DPP),
      in which a lifestyle intervention or metformin treatment was compared with
      placebo. METHODS: We genotyped the WFS1 SNPs rs10010131, rs752854 and rs734312
      (H611R) in 3,548 DPP participants and performed Cox regression analysis using
      genotype, intervention and their interactions as predictors of diabetes
      incidence. We also evaluated the effect of these SNPs on insulin resistance and
      beta cell function at 1 year. RESULTS: Although none of the three SNPs was
      associated with diabetes incidence in the overall cohort, white homozygotes for
      the previously reported protective alleles appeared less likely to develop
      diabetes in the lifestyle arm. Examination of the publicly available Diabetes
      Genetics Initiative genome-wide association dataset revealed that rs10012946,
      which is in strong linkage disequilibrium with the three WFS1 SNPs (r(2)=0.88
      1.0), was associated with type 2 diabetes (allelic odds ratio 0.85, 95% CI 0.75
      0.97, p=0.026). In the DPP, we noted a trend towards increased insulin secretion
      in carriers of the protective variants, although for most SNPs this was seen as
      compensatory for the diminished insulin sensitivity. CONCLUSIONS/INTERPRETATION:
      The previously reported protective effect of select WFS1 alleles may be magnified
      by a lifestyle intervention. These variants appear to confer an improvement in
      beta cell function.

PMID- 18060661
TI  - Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous
      adipose tissue lipolysis in lean and obese men.
AB  - AIMS/HYPOTHESIS: Obesity is characterised by increased triacylglycerol storage in
      adipose tissue. There is in vitro evidence for a blunted beta-adrenergically
      mediated lipolytic response in abdominal subcutaneous adipose tissue (SAT) of
      obese individuals and evidence for this at the whole-body level in vivo. We
      hypothesised that the beta-adrenergically mediated effect on lipolysis in
      abdominal SAT is also impaired in vivo in obese humans. METHODS: We investigated
      whole-body and abdominal SAT glycerol metabolism in vivo during 3 h and 6 h
      [2H5]glycerol infusions. Arterio-venous concentration differences were measured
      in 13 lean and ten obese men after an overnight fast and during intravenous
      infusion of the non-selective beta-adrenergic agonist isoprenaline [20 ng (kg fat
      free mass)(-1) min(-1)]. RESULTS: Lean and obese participants showed comparable
      fasting glycerol uptake by SAT (9.7+/-3.4 vs 9.3+/-2.5% of total release,
      p=0.92). Furthermore, obese participants showed an increased whole-body beta
      adrenergically mediated lipolytic response versus lean participants. However,
      their fasting lipolysis was blunted [glycerol rate of appearance: 7.3+/-0.6 vs
      13.1+/-0.9 micromol (kg fat mass)(-1) min(-1), p<0.01], as was the beta
      adrenergically mediated lipolytic response per unit SAT [Delta total glycerol
      release: 140+/-71 vs 394+/-112 nmol (100 g tissue)(-1) min(-1), p<0.05] compared
      with lean participants. Net triacylglycerol flux tended to increase in obese
      compared with lean participants during beta-adrenergic stimulation [Delta net
      triacylglycerol flux: 75+/-32 vs 16+/-11 nmol (100 g tissue)(-1) min(-1),
      p=0.06]. CONCLUSIONS/INTERPRETATION: We demonstrated in vivo that beta
      adrenergically mediated lipolytic response is impaired systematically and in
      abdominal SAT of obese versus lean men. This may be important in the development
      or maintenance of increased triacylglycerol stores and obesity.

PMID- 18060662
TI  - Effect of pressure support ventilation and positive end expiratory pressure on
      the rapid shallow breathing index in intensive care unit patients.
AB  - OBJECTIVE: We compared rapid shallow breathing index (RSBI) values under various
      ventilatory support settings prior to extubation. DESIGN AND SETTING: Prospective
      study in the intensive care unit at a university hospital. PATIENTS: Thirty six
      patients ready for extubation. INTERVENTIONS: Patients were enrolled when
      receiving pressure support ventilation (PSV) of 5 cmH2O, PEEP of 5 cmH2O, and
      FIO2 of 40% (PS). Subsequently each patient received a trial of PSV of 0 cmH2O,
      PEEP of 5 cmH2O, and FIO2 of 40% (CPAP), a trial of PSV of 0 cmH2O, PEEP of 5
      cmH2O and FIO2 of 21% (CPAP-R/A), and a 1-minute spontaneously breathing room air
      trial off the ventilator (T-piece). Trials were carried out in random order.
      MEASUREMENTS AND RESULTS: Respiratory frequency (f) and tidal volume (VT) were
      measured during PS, CPAP, CPAP-R/A, and T-piece in all patients. RSBI (f/VT) was
      determined for each patient under all experimental conditions, and the average
      RSBI was compared during PS, CPAP, CPAP-R/A, and T-piece. RSBI was significantly
      smaller during PS (46+/-8 bpm/l), CPAP (63+/-13 bpm/l) and CPAP-R/A (67+/-14
      bpm/l) vs. T-piece (100+/-23 bpm/l). There was no significant difference in RSBI
      between CPAP and CPAP-R/A. RSBI during CPAP and CPAP-R/A were significantly
      smaller than RSBI during T-piece. In all patients RSBI values were less than 105
      bpm/l during PS, CPAP, and CPAP-R/A. However, during T-piece the RSBI increased
      to greater than 105bpm/l in 13 of 36 patients. CONCLUSIONS: In the same patient
      the use of PSV and/or PEEP as low as 5 cmH2O can influence the RSBI. In contrast,
      changes in FIO2 may have no effect on the RSBI.

PMID- 18060664
TI  - Transcriptional response of Desulfovibrio vulgaris Hildenborough to oxidative
      stress mimicking environmental conditions.
AB  - Sulfate-reducing bacteria (SRB) are anaerobes readily found in oxic-anoxic
      interfaces. Multiple defense pathways against oxidative conditions were
      identified in these organisms and proposed to be differentially expressed under
      different concentrations of oxygen, contributing to their ability to survive oxic
      conditions. In this study, Desulfovibrio vulgaris Hildenborough cells were
      exposed to the highest concentration of oxygen that SRB are likely to encounter
      in natural habitats, and the global transcriptomic response was determined. Three
      hundred and seven genes were responsive, with cellular roles in energy
      metabolism, protein fate, cell envelope and regulatory functions, including
      multiple genes encoding heat shock proteins, peptidases and proteins with heat
      shock promoters. Of the oxygen reducing mechanisms of D. vulgaris only the
      periplasmic hydrogen-dependent mechanism was up-regulated, involving the [NiFeSe]
      hydrogenase, formate dehydrogenase(s) and the Hmc membrane complex. The oxidative
      defense response concentrated on damage repair by metal-free enzymes. These data,
      together with the down-regulation of the ferric uptake regulator operon, which
      restricts the availability of iron, and the lack of response of the peroxide
      sensing regulator operon, suggest that a major effect of this oxygen stress is
      the inactivation and/or degradation of multiple metalloproteins present in D.
      vulgaris as a consequence of oxidative damage to their metal clusters.

PMID- 18060663
TI  - Angiotensin-converting enzyme insertion/deletion polymorphism is not associated
      with susceptibility and outcome in sepsis and acute respiratory distress
      syndrome.
AB  - OBJECTIVE: The insertion/deletion (I/D) of a 289 base pair Alu repeat sequence
      polymorphism in the angiotensin-converting enzyme gene (ACE) has been shown to
      predict susceptibility and outcome in the acute respiratory distress syndrome
      (ARDS). We hypothesized that the I/D polymorphism also confers susceptibility to
      sepsis and is a predisposing factor for morbidity and mortality of patients with
      severe sepsis. DESIGN AND SETTING: Case-control study including 212 consecutive
      patients fulfilling criteria for severe sepsis admitted to a Spanish network of
      postsurgical and critical care units, and 364 population-based controls.
      Susceptibility to severe sepsis was evaluated as primary outcome; mortality in
      severe sepsis, susceptibility to sepsis-induced ARDS, and mortality in sepsis
      induced ARDS were examined as secondary outcomes. An additive model of
      inheritance in which patients were classified into three genotype groups (II, ID,
      and DD) was used for association testing. MEASUREMENTS AND RESULTS: Genotype and
      allele frequencies of I/D were distributed similarly in all septic, ARDS, and non
      ARDS patients and in population-based controls. ACE I/D polymorphism was not
      associated with severe sepsis susceptibility or mortality. The ACE I/D
      polymorphism was associated neither with sepsis-induced ARDS susceptibility
      (p=0.895) or mortality (p=0.950). These results remained nonsignificant when
      adjusted for other covariates using multiple logistic regression analysis or
      Kaplan-Meier estimates of 28-day survival. CONCLUSIONS: Our data do not support
      an association of the ACE gene I/D polymorphism with susceptibility or mortality
      in severe sepsis or with sepsis-induced ARDS in Spanish patients.

PMID- 18060665
TI  - Characterization of a 30S ribosomal subunit assembly intermediate found in
      Escherichia coli cells growing with neomycin or paromomycin.
AB  - Neomycin and paromomycin are aminoglycoside antibiotics that specifically
      stimulate the misreading of mRNA by binding to the decoding site of 16S rRNA in
      the 30S ribosomal subunit. Recent work has shown that both antibiotics also
      inhibit 30S subunit assembly in Escherichia coli and Staphylococcus aureus cells.
      This work describes the characteristics of an assembly intermediate produced in
      E. coli cells grown with neomycin or paromomycin. Antibiotic treatment stimulated
      the accumulation of a 30S assembly precursor with a sedimentation coefficient of
      21S. The particle was able to bind radio-labeled antibiotics in vivo and in
      vitro. Hybridization experiments showed that the 21S precursor particle contained
      unprocessed 16S rRNA with both 5' and 3' extensions. Ten 30S ribosomal proteins
      were found in the precursor after inhibition by each drug. In addition, cell free
      reconstitution assays generated a 21S particle after incubation with either
      aminoglycoside. This work helps to define the features of the ribosome structure
      as a target for antimicrobial agents and may provide information needed for the
      design of more effective antibiotics.

PMID- 18060666
TI  - Validation of a Tn5 transposon mutagenesis system for Gluconacetobacter
      diazotrophicus through characterization of a flagellar mutant.
AB  - Gluconacetobacter diazotrophicus is a nitrogen-fixing bacterium, which was
      originally isolated from the interior of sugarcane plants. The genome of strain
      PAL5 of G. diazotrophicus has been completely sequenced and a next step is the
      functional characterization of its genes. The aim of this study was to establish
      an efficient mutagenesis method, using the commercial Tn5 transposon EZ::Tn5<KAN
      2>Tnp Transposome (Epicentre). Up to 1 x 10(6) mutants per microgram of
      transposome were generated in a single electroporation experiment. Insertion-site
      flanking sequences were amplified by inverse PCR and sequenced for 31 mutants.
      For ten of these mutants, both insertion flanks could be identified, confirming
      the 9 bp duplication that is typical for Tn5 transposition. Insertions occurred
      in a random fashion and were genetically stable for at least 50 generations. One
      mutant had an insertion in a homolog of the flagellar gene flgA, and was
      therefore predicted to be affected in flagella-dependent traits and used to
      validate the applied mutagenesis methodology. This mutant lacked flagella and was
      non-motile on soft agar. Interestingly, it was also strongly affected in the
      ability to form biofilm on glass wool.

PMID- 18060667
TI  - Cloning and expression of trypanothione reductase from a New World Leishmania
      species.
AB  - Trypanothione disulfide (T[S]2), an unusual form of glutathione found in
      parasitic protozoa, plays a crucial role in the regulation of the intracellular
      thiol redox balance and in the defense against oxidative stress. Trypanothione
      reductase (TR) is central to the thiol metabolism in all trypanosomatids,
      including the human pathogens Trypanosoma cruzi, Trypanosoma brucei and
      Leishmania. Here we report the cloning, sequencing and expression of the TR
      encoding gene from L. (L.) amazonensis. Multiple protein sequence alignment of
      all known trypanosomatid TRs highlights the high degree of conservation and
      illustrates the phylogenetic relationships. A 3D homology model for L.
      amazonensis TR was constructed based on the previously reported Crithidia
      fasciculata structure. The purified recombinant TR shows enzyme activity and in
      vivo expression of the native enzyme could be detected in infective
      promastigotes, both by Western blotting and by immunofluorescence.

PMID- 18060668
TI  - Pressure gradient and subsurface shear stress on the neuropathic forefoot.
AB  - BACKGROUND: Stresses within the neuropathic foot's tissues can be estimated by
      pressure distributions and may provide information regarding the potential for
      skin breakdown. The purposes of this study were to: (1) determine the magnitude
      of peak plantar pressure, pressure time integral, peak pressure gradient, and
      peak maximum shear stress; and (2) determine the association of these variables
      with one another. METHODS: Forefoot peak plantar pressure, pressure time
      integral, peak pressure gradient, peak maximal shear stress, and depth of peak
      maximal shear stress were calculated for 16 controls, 16 people with diabetic
      neuropathy, and 22 people with diabetic neuropathy and a history of ulceration
      from pressure assessments. FINDINGS: Peak plantar pressure, pressure gradient,
      and maximal shear stress were greater in subjects with a history of ulceration
      relative to control subjects (P<0.03), pressure gradient was greater in subjects
      with diabetic neuropathy and a history of ulceration compared to subjects with
      diabetic neuropathy and no history of ulceration (P<0.02), and depth of maximal
      shear stress was less in both groups of subjects with diabetic neuropathy
      compared to controls (P<0.03). Strong relationships existed between the
      variables. INTERPRETATION: Although these variables are associated with one
      another, peak pressure gradient and peak maximal shear stress provide information
      concerning plantar pressure distribution and the potentially injurious internal
      stresses within the foot's soft tissues. Peak pressure gradient and peak maximal
      shear stress may perhaps be more discriminating than peak plantar pressure alone
      in distinguishing between groups of individuals who are at risk for developing a
      foot ulcer.

PMID- 18060670
TI  - Arbuscular mycorrhiza enhanced arsenic resistance of both white clover (Trifolium
      repens Linn.) and ryegrass (Lolium perenne L.) plants in an arsenic-contaminated
      soil.
AB  - In a compartmented cultivation system, white clover (Trifolium repens Linn.) and
      ryegrass (Lolium perenne L.), with their roots freely intermingled, or separated
      by 37 microm nylon mesh or plastic board, were grown together in an arsenic (As)
      contaminated soil. The influence of AM inoculation on plant growth, As uptake,
      phosphorus (P) nutrition, and plant competitions were investigated. Results
      showed that both plant species highly depended on mycorrhizas for surviving the
      As contamination. Mycorrhizal inoculation substantially improved plant P
      nutrition, and in contrast markedly decreased root to shoot As translocation and
      shoot As concentrations. It also showed that mycorrhizas affected the competition
      between the two co-existing plant species, preferentially benefiting the clover
      plants in term of nutrient acquisition and biomass production. Based on the
      present study, the role of AM fungi in plant adaptation to As contamination, and
      their potential use for ecological restoration of As contaminated soils are
      discussed.

PMID- 18060669
TI  - Examining outcomes from total knee arthroplasty and the relationship between
      quadriceps strength and knee function over time.
AB  - BACKGROUND: Temporal-spatial gait parameters improve following total knee
      arthroplasty (TKA) but lower limb kinematics and moments fail to match those of
      age-matched healthy individuals. The aim of this study was to determine whether
      quadriceps strength, clinical measures of knee function, lower limb kinematics,
      and joint moments improve following arthroplasty and normalize over time.
      METHODS: Twelve patients underwent total knee arthroplasty were tested at 3 and
      12 months following surgery. Twelve matched controls were also tested. All
      underwent quadriceps strength testing and gait analysis to calculate knee joint
      kinematics and kinetics. Function was assessed using clinical tests and self
      report. FINDINGS: All clinical measures except for quadriceps strength
      significantly improved from 3 to 12 months. Gait asymmetry was observed at 3
      months (lower stance times, peak knee flexion angle, range of motion and vertical
      ground reaction force), but ankle, knee and hip moments contributing to the total
      limb support moment were equivalent between legs. At 12 months, gait speed
      remained significantly slower than controls. Inter-limb differences in peak knee
      flexion angle and range of motion persisted. Greater hip and lower knee moments
      were evident in the operated limb, compared to the non-operated limb and
      controls. Quadriceps strength was positively correlated with faster times on the
      Time Up and Go and Stair Climbing Test and greater distances during the 6 Minute
      Walk test. INTERPRETATION: Patients who have undergone TKA demonstrate
      improvements in function as measured by self-report and functional performance
      measures. Gait becomes more symmetric and quadriceps strength becomes stronger.
      Some approached the values of healthy control subjects. Important differences
      still remain however. The larger hip extensor contribution to the total support
      moment may be to compensate for the diminished knee extensor contribution during
      level walking. Since instrumented gait analysis and functional performance
      measures appear to reflect different aspects of recovery following total knee
      replacement, both should be considered when evaluating gait and function.

PMID- 18060671
TI  - Estimation of nitrogen balance between the atmosphere and Lake Balaton and a semi
      natural grassland in Hungary.
AB  - The paper summarises the results to determine the fluxes of different N-compounds
      within the atmosphere and an aquatic and a terrestrial ecosystems, in Hungary. In
      the exchange processes of N-compounds between atmosphere and various ecosystems
      the deposition dominates. The net deposition fluxes are -730, -1270 and -1530 mg
      Nm(-2)yr(-1) for water, grassland, and forest ecosystems, respectively. For
      water, the main source of nitrogen compounds is the wet deposition. Ammonia gas
      is close to the equilibrium between the water and the air. For grassland the dry
      flux of nitric acid and ammonia is also an important term beside the wet
      deposition. Dry deposition to terrestrial ecosystems is roughly two times higher
      than wet deposition. A total of 8-10% of the nitrates and NH(x) deposited to
      terrestrial ecosystems are re-emitted into the air in the form of nitrous oxide
      (N2O) greenhouse gas.

PMID- 18060672
TI  - Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta
      analysis.
AB  - A meta-analysis of the efficacy of cognitive behavioral therapy (CBT) in treating
      chronic fatigue included 15 effect sizes for between-group outcome comparisons.
      Across analyses, which included a total of 1371 participants, there was a
      significant difference, d=0.48, in post-treatment fatigue between participants
      receiving CBT and those in control conditions. Results indicate that CBT for
      chronic fatigue syndrome tends to be moderately efficacious. Dropout rates in CBT
      varied from 0-42%, with a mean of 16%. In the five studies that reported the
      number of CBT clients who were no longer in the clinical range with regard to
      fatigue at the latest follow-up, the percentage varied from 33% to 73% of those
      assigned to CBT, with a mean of 50%. Moderator results suggest directions for
      future investigations.

PMID- 18060673
TI  - Assessment of user safety, exposure and risk to veterinary medicinal products in
      the European Union.
AB  - Safety is an important part of veterinary drug assessment while user safety is a
      critical part of the overall safety assessment. In the European Union (EU), user
      safety is addressed through preclinical studies and by relationships with
      exposure but a key part of the process is the user safety assessment. EU user
      safety guidelines are available and these make certain recommendations but in
      places they lack detail and clarity. This paper seeks to examine the relevant
      factors that lie behind user risk assessments for veterinary medicinal products
      in general while focusing on EU requirements, the determination of risk
      management and risk communication strategies and how this relates to user safety
      assessment and pharmacovigilance responsibilities.

PMID- 18060674
TI  - The search for asbestos within the Peter Mitchell Taconite iron ore mine, near
      Babbitt, Minnesota.
AB  - Asbestos crystallizes within rock formations undergoing intense deformation
      characterized by folding, faulting, shearing, and dilation. Some of these
      conditions have prevailed during formation of the taconite iron ore deposits in
      the eastern Mesabi Iron Range of Minnesota. This range includes the Peter
      Mitchell Taconite Mine at Babbitt, Minnesota. The mine pit is over 8 miles long,
      up to 1 mile wide. Fifty three samples were collected from 30 sites within areas
      of the pit where faulting, shearing and folding occur and where fibrous minerals
      might occur. Eight samples from seven collecting sites contain significant
      amounts of ferroactinolite amphibole that is partially to completely altered to
      fibrous ferroactinolite. Two samples from two other sites contain ferroactinolite
      degraded to ropy masses of fibers consisting mostly of ferrian sepiolite as
      defined by X-ray diffraction and TEM and SEM X-ray spectral analysis. Samples
      from five other sites contain unaltered amphiboles, however some of these samples
      also contain a very small number of fiber bundles composed of mixtures of
      grunerite, ferroactinolite, and ferrian sepiolite. It is proposed that the
      alteration of the amphiboles was caused by reaction with water-rich acidic fluids
      that moved through the mine faults and shear zones. The fibrous amphiboles and
      ferrian sepiolite collected at the Peter Mitchell Mine composes a tiny fraction
      of one percent of the total rock mass of this taconite deposit; an even a smaller
      amount of these mineral fragments enter the ambient air during mining and
      milling. These fibrous minerals thus do not present a significant health hazard
      to the miners nor to those non-occupationally exposed. No asbestos of any type
      was found in the mine pit.

PMID- 18060676
TI  - Effect of dietary fat-soluble vitamins A and E and proanthocyanidin-rich extract
      from grape seeds on oxidative DNA damage in rats.
AB  - This study reports the effect of the fat-soluble vitamin A or vitamin E and grape
      seed proanthocyanidin extract (GSPE) on oxidative DNA damage estimated by 8-oxo
      7, 8-dihydro-2'-deoxyguanosine (8-oxodG) contents in urine and leukocyte of rats.
      Little is known about the antioxidant potency of dietary anthocyanidins and
      consequently, the aim of this study was to establish whether anthocyanidins could
      act as putative antioxidant micronutrients. Seven groups of male Sprague-Dawley
      rats were fed during 47 days with the following diets: a basic diet, two
      deficient vitamin A or E diets, two supplemented vitamin A or E diets and two
      supplemented diets enriched with two doses of grape seed proanthocyanidin
      extract. At the end of the diet intervention period, 24h, urine and blood were
      collected. The levels of 8-oxodG in leukocytes rats were significantly lower in
      the supplemented vitamin A, E and GSPE diet groups with respect to the control
      group. However, consumption of alpha-tocopherol, vitamin A or GSPE had no effect
      on the excretion of the oxidised nucleoside 8-oxodG. These results suggest that a
      vitamin E and A and GSPE enriched-diets have a protective effect on oxidative DNA
      damage limited to rat leukocytes.

PMID- 18060675
TI  - Associations between increases in plasma n-3 polyunsaturated fatty acids
      following supplementation and decreases in anger and anxiety in substance
      abusers.
AB  - OBJECTIVE: Mounting evidence indicates that low levels of n-3 polyunsaturated
      fatty acids (PUFAs) play a role in the pathophysiology of a large number of
      psychiatric disorders. In light of the suboptimal n-3 PUFAs intake due to poor
      dietary habits among substance abusers and the strong associations between
      aggression, anxiety and substance use disorders we examined if insurance of
      adequate intakes of n-3 PUFAs with supplementation would decrease their anger and
      anxiety scores. METHOD: Substance abusers (n=22) were assigned to either 3 g of n
      3 PUFAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or
      soybean oil in identically looking capsules. The trial was double-blind,
      randomized and lasted 3 months. Anger and anxiety scales were administered at
      baseline and once a month thereafter. Blood samples were collected at baseline
      and at the end of the trial. RESULTS: Patients' dietary intakes of n-3 PUFAs fell
      below recommended levels. Assignment to n-3 PUFA treatment was accompanied by
      significant decreases in anger and anxiety scores compared to placebo assignment.
      These changes were associated with increases in plasma levels of both EPA and DHA
      but an increase in EPA was more robustly correlated with low end-of-trial anxiety
      scores and an increase in DHA was more robustly correlated with low end-of-trial
      anger scores. CONCLUSION: These pilot data indicate that ensuring adequate n-3
      PUFA intake via supplementation benefits substance abusers by reducing their
      anger and anxiety levels. The strong correlations between an increase in plasma
      EPA and lower anxiety scores and between an increase in plasma DHA and lower
      anger scores suggests a need for the further exploration of the differential
      responses to these two n-3 PUFAs in different psychiatric conditions.

PMID- 18060677
TI  - Optimized mismatch negativity paradigm reflects deficits in schizophrenia
      patients. A combined EEG and MEG study.
AB  - Mismatch negativity (MMN) and its neuromagnetic analog (MMNm) are event-related
      brain responses elicited by changes in a sequence of auditory events and indexes
      early cognitive processing. It consistently detects neural processing deficits in
      schizophrenia. So far MMN is assessed with different methods
      (electroencephalography, EEG; magnetoencephalography, MEG) and with different
      paradigms: the "traditional" oddball design with rare deviants (20%) or the
      "optimum" design with 50% deviants varying in one of five parameters each. These
      MMN measures may not reflect one unitary mechanism which is equally affected in
      schizophrenia. We compared both designs in 12 patients with schizophrenia and
      controls using MEG and EEG. Automated, observer-independent data analysis
      rendered the procedures suitable for clinical applications. The optimum design
      was fastest to detect MMN and MEG had the best signal-to-noise ratio. In addition
      MMN was mostly reduced in schizophrenia if measured with MEG in the optimum
      paradigm. Optimized paradigms improve sensitivity and speed for the detection of
      schizophrenia endophenotypes. Dysfunctions in this disorder may lie primarily in
      the fast and automatic encoding of stimulus features at the auditory cortex.

PMID- 18060679
TI  - Quantitation of the molecular mechanisms of biological synergism in a mixture of
      DNA-acting aromatic drugs.
AB  - It is suggested that the widely reported biological synergism of a mixture of DNA
      targeting aromatic drug molecules both in vivo and in vitro can be explained, in
      part, at the molecular level by competition between two basic mechanisms: the
      'interceptor' (hetero-association between Drug1 and Drug2) and 'protector'
      mechanisms (complexation of Drug1 and Drug2 on DNA-binding sites). In the present
      work a complete analytical methodology has been developed to quantify these
      processes, providing an estimate of the relative importance of the
      interceptor/protector mechanisms using just a set of equilibrium association
      constants. The general methodology may be applied to other molecules with
      receptors for aromatic drugs.

PMID- 18060680
TI  - Splitting and lumping adult renal epithelial tumours: is that what the urologists
      want?

PMID- 18060681
TI  - Prognostic significance of Gleason score discrepancies between needle biopsy and
      radical prostatectomy.
AB  - OBJECTIVES: Discordance between the Gleason score (GS) on needle biopsy (NB) and
      the GS of the radical prostatectomy (RP) specimen is a common finding. The
      objective of this study was to evaluate the prognostic significance of these
      discrepancies with respect to outcomes following RP. METHODS: In the study, 6625
      men treated by RP were categorized as having NB=RP (68.8%), NB<RP (25.0%) or
      NB>RP (6.2%) GS, and stratified for analyses into RP GS groups. The Kaplan-Meier
      method was used to analyze differences in biochemical recurrence-free survival
      (BRFS), and multivariate Cox analyses were performed to estimate the independent
      relative risk of progression associated with GS discrepancies. RESULTS: Across
      multiple RP GS strata (3+4, 7, 8, 8-10), patients with a lower NB GS experienced
      significantly better BRFS than patients with equal NB and RP GS (all p<0.05).
      NB<RP GS was independently associated with better (pooled HR, 0.76, p=0.001)
      BRFS, within and across RP GS strata. Similarly, patients with NB>RP GS had
      poorer BRFS than patients with NB=RP GS across multiple RP GS strata (< or =3+3,
      3+4, 7; all p<0.05). NB>RP GS was independently associated with worse (pooled HR,
      1.91, p<0.001) BRFS probabilities, within and across RP GS strata. CONCLUSIONS:
      Our data suggest that the GS of the NB adds additional prognostic value to the RP
      GS in a consistent manner that may be applicable to strategies of risk
      stratification and patient counseling after surgery.

PMID- 18060683
TI  - Tumor size and nephron-sparing surgery: does it still matter?

PMID- 18060685
TI  - Dandy Walker malformation associated with syringomyelia.

PMID- 18060684
TI  - Pre-receptor regulation of the androgen receptor.
AB  - The human androgen receptor (AR) is a ligand-activated nuclear transcription
      factor and mediates the induction of genes involved in the development of the
      male phenotype and male secondary sex characteristics, as well as the normal and
      abnormal growth of the prostate. We have identified the pair of hydroxysteroid
      dehydrogenases (HSDs) that regulate ligand access to the AR in human prostate. We
      find that type 3 3alpha-HSD (aldo-keto reductase (AKR)1C2) catalyzes the NADPH
      dependent reduction of the potent androgen 5alpha-dihydrotestosterone (5alpha
      DHT) to yield the inactive androgen 3alpha-androstanediol (3alpha-diol). We also
      find that RoDH like 3alpha-HSD (RL-HSD) catalyzes the NAD(+) dependent oxidation
      of 3alpha-diol to yield 5alpha-DHT. Together these enzymes are involved in the
      pre-receptor regulation of androgen action. Inhibition of AKR1C2 would be
      desirable in cases of androgen insufficiency and inhibition of RL-HSD might be
      desirable in benign prostatic hyperplasia.

PMID- 18060686
TI  - Two types of squamous cell carcinoma of the palatine tonsil characterized by
      distinct etiology, molecular features and outcome.
AB  - To determine whether human papillomaviruses (HPV) positive tonsillar squamous
      cell carcinoma (SCC) represent a specific entity, we studied the prevalence of
      HPV association and of tobacco/alcohol exposure in a series of 52 cases of
      tonsillar SCC cases. p53, p16, and pRb levels, deregulated by viral oncoproteins
      were assessed. Forty patients reported tobacco/alcohol exposure, 10 reported no
      exposure. HPV DNA was found in 32/52 (62%) cases, (HPV16 genotype in 27). All
      patients with no history of tobacco-alcohol exposure presented HPV positive tumor
      (p=0.0008). A strong correlation was observed between positive HPV status,
      decrease in pRB and increase in p16 expression level. 5 year overall survival
      rate was higher in HPV16 positive patients than in HPV negative (71% versus 36%;
      p=0.023). HPV status remained a significant prognostic factor in multivariate
      analysis. Tonsillar SCC can thus be divided in HPV positive and negative
      subgroups with different oncogenesis and response to treatment.

PMID- 18060687
TI  - B cell lymphomas express CX3CR1 a non-B cell lineage adhesion molecule.
AB  - To study the differential expression of cell membrane-bound receptors and their
      potential role in growth and/or survival of the tumor cells, highly purified
      follicular lymphoma cells were analyzed, using gene expression analysis, and
      compared to non-malignant B cell populations. Filtering the genome for
      overexpressed genes coding for cell membrane-bound proteins/receptors resulted in
      a hit list of 27 identified genes. Among these, we have focused on the aberrant
      over expression of CX3CR1, in different types of B cell lymphoma, as compared to
      non-malignant B cells. We show that CX3CR1, which normally is not expressed on B
      cells, is expressed both at the mRNA and protein level in several subtypes of
      lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues
      that express the ligand, CX3CL1, in breast and prostate cancer and may thus be
      involved in dissemination of lymphoma.

PMID- 18060688
TI  - The interaction of DNR and glutaraldehyde with cell membrane proteins leads to
      morphological changes in erythrocytes.
AB  - In this study, the effects of DNR and glutaraldehyde on isolated erythrocyte
      membrane proteins were examined. For this purpose, SDS-gel electrophoresis was
      carried out. Additionally, analyses of the disturbances in erythrocyte shape and
      size, accompanied by the application of flow cytometry and microscopy
      examination, were undertaken. The amount of DNR linked to erythrocyte cell
      membranes was measured by a fluorimetric technique. It was observed that
      glutaraldehyde caused in concentration dependent manner an increase of percent of
      DNR linked to cell membrane proteins. After this incorporation, perturbations in
      the protein content of cell membranes were observed. The protein aggregates and
      changes in the level of spectrin, actin and band 3 protein were noted. Due to the
      changes in spectrin, which is mainly responsible for maintenance of the discocyte
      shape of erythrocytes, flow cytometry and microscopy techniques were used to
      control the size and shape of erythrocytes after treatment with DNR and
      glutaraldehyde. The disturbances in the shape and size of erythrocytes were
      observed for all tested concentrations of glutaraldehyde. For all tested
      concentrations of glutaraldehyde, the changes were statistically significant.

PMID- 18060689
TI  - Governing factors for motor oil removal from water with different sorption
      materials.
AB  - This paper has been focused on the sorbent efficiency for motor oil removal from
      water. Two types of sorbents were investigated: organic and inorganic. Natural
      wool fibers (NWFs) and recycled-wool-based nonwoven material (RWNM)) were tested
      as organic type of sorbents. Sepiolite, bentonite and zeolite have been chosen as
      representative inorganic sorbents. Sorption was carried out in batch sorption
      system. Efficiency of oil removal was determined by measuring the oil
      concentration before and after the sorption process. Extractive-gravimetric
      method and refractive index determination have been applied as analytical methods
      for determination of oil concentration in water. Governing factors for sorbent
      efficiency were proposed, analysed and compared. It was concluded that sorption
      process is mostly affected by mass of sorbent, sorption time, temperature and pH
      value of water. NWFs, which were the most efficient sorbent showed maximal
      efficiency and maximal sorption capacity: 0.1 g of NWFs after 10 min at 20
      degrees C and pH 8.00 sorbed 3.3 g of motor oil from 300 mL of water polluted
      with 4.5 g of motor oil. Maximal efficiency for all sorbents investigated was
      reached after 30 min of sorption processes, it was 95.0% for NWF, 43.0% for NRWM,
      20.7% for sepiolite, 19.6% for bentonite and 21.2% for zeolite. Physical
      adsorption onto all sorbents is a favorable process (sorption efficiency decrease
      with increasing temperature) while sorption onto bentonite and zeolite is a
      result of both physical adsorption and chemisorption (sorption efficiency
      increase with increasing temperature, up to 80 degrees C).

PMID- 18060690
TI  - Synthesis of RDX by nitrolysis of hexamethylenetetramine in fluorous media.
AB  - Perfluorooctanesulfonic acid (CF(3)(CF(2))(7)SO(3)H, PfOS) catalyses the highly
      efficient nitrolysis of hexamethylenetetramine in fluorous media, affording high
      yield of explosive RDX. The reaction can be carried out at room temperature in
      the absence of acetic anhydride and produces smaller amounts of waste acid and
      nitrate than in traditional process. The fluorous phase containing catalyst could
      be easily and efficiently recovered for reuse by simple phase separation.

PMID- 18060691
TI  - Metal recovery from spent hydrodesulfurization catalysts using a combined acid
      leaching and electrolysis process.
AB  - This study focuses on recovering valuable metals from spent hydrodesulfurization
      (HDS) catalysts using a combined acid-leaching and fluidized-bed electrolysis
      process. The electrolytic cell was equipped with a glass bead medium, an iridium
      oxide mesh anode, and a stainless steel plate cathode. An acid solution
      consisting of concentrated HNO3/H2SO4/HCl with a volume ratio of 2:1:1 was found
      to be better than the other tested solution (HNO3/H2SO4=1:1) to leach the metals.
      For the three-acid mixture, the best solid/liquid ratio and leaching time were 40
      g/L and 1 h, respectively, at 70 degrees C; under this condition, the leaching
      yields of target metals (Mo, Ni, and V) in the 1st stage of leaching reached 90,
      99, and 99%, respectively, much higher than those in the 2nd/3rd/4th stages. When
      this acid leachate was electrolyzed for 2 h at 2 A constant current (current
      density=approximately 35.7 mA/cm2), a stable cell voltage of 5 V was observed.
      The electrolytic recoveries of Mo, Ni, and V were approximately 15, 61, and 66%,
      respectively, but extending the electrolysis time from 2 to 4 h did not increase
      the recoveries. For this operation, the total recoveries (leaching
      yieldxelectrolytic recovery) of Mo, Ni, and V were approximately 14, 60, and 65%,
      respectively.

PMID- 18060692
TI  - Safety climate practice in Korean manufacturing industry.
AB  - Safety climate survey was sent to 642 plants in 2003 to explore safety climate
      practices in the Korean manufacturing plants, especially in hazardous chemical
      treating plants. Out of 642 plants contacted 195 (30.4%) participated in the
      surveys. Data were collected by e-mail using SQL-server and mail. The main
      objective of this study was to explore safety climate practices (level of safety
      climate and the underlying problems). In addition, the variables that may
      influence the level of safety climate among managers and workers were explored.
      The questionnaires developed by health and safety executive (HSE) in the UK were
      modified to incorporate differences in Korean culture. Eleven important factors
      were summarized. Internal reliability of these factors was validated. Number of
      employees in the company varied from less than 30 employees (9.2%) to over 1000
      employees (37.4%). Both managers and workers showed generally high level of
      safety climate awareness. The major underlying problems identified were
      inadequate health and safety procedures/rules, pressure for production, and rule
      breaking. The length of employment was a significant contributing factor to the
      level of safety climate. In this study, participants showed generally high level
      of safety climate, and length of employment affected the differences in the level
      of safety climate. Managers' commitment to comply safety rules, procedures, and
      effective safety education and training are recommended.

PMID- 18060693
TI  - Study on the generation of perfluorooctane sulfonate from the aqueous film
      forming foam.
AB  - Perfluorooctane sulfonate (C(8)HF(17)SO(3)) and perfluorooctane acid
      (C(8)HF(15)O(2)) are artificial chemicals and have been used all over the world,
      mainly as water repellent agents, fluorochemical surfactants, coating agents,
      etc. However, perfluorooctane sulfonate and perfluorooctane acid are
      environmental contaminants because of their stability, bio-accumulativeness, and
      long-term persistence in the ecological environment. At the present day, they are
      diffused all over the world. Lately, this diffusion is viewed with suspicion and
      there is a movement towards their restriction, even if the environmental fate of
      them is still under investigation. Fluorochemical surfactants are key compounds
      in the aqueous film-forming foam (AFFF) formulations. AFFFs are used for massive
      conflagration such as industrial fire and petroleum fire because of their
      efficient fire control. On the other hand, a lot of AFFFs are used in case of
      massive conflagration and most of them enter ocean and groundwater. Actually,
      perfluorooctane sulfonate and perfluorooctane sulfonate related substances were
      detected from the fire-fighting facility of US forces. Therefore, there is the
      possibility of generating perfluorooctane sulfonate and perfluorooctane sulfonate
      related substances from fluorochemical surfactants in the AFFFs. In this study,
      activated sludge added AFFF were analyzed for perfluorooctane sulfonate and
      perfluorooctane acid with time. And the perfluorooctane sulfonate was directly
      detected after 2 days using LC-MS. This shows that AFFF can be decomposed
      perfluorooctane sulfonate by microorganisms easily. However, perfluorooctane
      sulfonate would not decompose at all. Additionally, activated sludge added N
      polyoxyethylene-N-propyl perfluorooctane sulfonamide which is one of the
      fluorochemical surfactants used in the AFFF was analyzed for perfluorooctane
      sulfonate and perfluorooctane acid with time and the perfluorooctane sulfonate
      was detected too.

PMID- 18060694
TI  - Removal of boron from refined brine by using selective ion exchange resins.
AB  - Boron removal by ion exchange resin from refined brine which was used to produce
      low-boron lithium salts was studied. A new boron-specific resin, XSC-800 was used
      in the experiments for the separation of boron. The column-mode and batch-mode
      sorption studies were both performed so as to obtain the optimum conditions for
      boron removal from refined brine. Parameters such as flow rate of brine, boron
      concentration, temperature, pH, height/diameter (H/D) ratio of the column, anion
      concentration, stirring speed and diameter of the resin were investigated. The
      results showed that the removal effect of boron by XSC-800 improved with
      increasing temperature, pH, H/D ratio, and with decreasing the flow rate of
      brine, boron concentration, chloride anion concentration and diameter of the
      resin. While the stirring speed and the recycles of the resin had no significant
      effects on boron removal. As a result, boron can be removed from refined brine
      much completely by the resin at the optimum conditions. On the other hand,
      kinetics of the exchange process was studied by using the moving boundary model.
      In order to describe the kinetics more accurately, the model was modified by
      introducing a time correction factor. The results showed that the rate
      determining step of this process under the conditions studied was controlled by
      particle diffusion. In addition, the apparent activation energy Ea of the process
      was found to be 20.38 kJ/mol.

PMID- 18060695
TI  - What were they thinking? Cognitive states may influence [11C]raclopride binding
      potential in the striatum.
AB  - [(11)C]Raclopride ([(11)C]RAC) is a selective dopamine D(2)/D(3) antagonist that
      is commonly used in positron emission tomography (PET) studies to assess both
      basal levels of receptor availability and changes in availability caused by
      alterations in striatal dopamine concentration. When designing [(11)C]RAC
      studies, it is important to understand what variables may affect the results.
      Here, we examined differences in baseline striatal [(11)C]RAC binding potential
      (BP(ND)) under two different "rest" conditions. Thirteen subjects received
      [(11)C]RAC scans. Eight subjects were aware prior to initiation of scanning that
      they would receive a "baseline" scan, and that no additional procedures would
      take place during the scan ("certain rest" group, CER). Five subjects were
      informed that they might or might not receive an i.v. alcohol infusion during the
      scan ("uncertain rest" group, UNC). This group was informed five min after scan
      start that they would not receive alcohol. Voxel-wise analyses of binding
      potential (BP(ND)) images generated for both "rest" conditions indicated that
      receptor availability was higher in UNC than in CER. This result was confirmed by
      a region-of-interest analysis, which indicated that the average BP(ND) in right
      and left putamen was statistically higher in UNC. There were no differences in
      groups with respect to age or raclopride mass dose that could account for the
      difference in D(2)/D(3) receptor availability. Our findings suggest that even
      slight differences in cognitive states between groups can have an effect on
      BP(ND), presumably mediated by changes in endogenous dopamine concentration.

PMID- 18060696
TI  - Cross-desensitization of responses of rat trigeminal subnucleus caudalis neurons
      to cinnamaldehyde and menthol.
AB  - Most cold-sensitive subnucleus caudalis (Vc) neurons are also excited by the
      TRPM8 agonist menthol and the TRPA1 agonist cinnamaldehyde (CA). We investigated
      how interactions among menthol, CA and noxious cooling and heating of the tongue
      affected responses of superficial Vc units recorded in thiopental-anesthetized
      rats. Units responded to 1% CA which enhanced cold- and heat-evoked responses 5
      min later. They responded more strongly to 10% CA which initially depressed cold
      responses, followed by enhancement at 5 min without affecting responses to heat.
      Following 10% CA, the mean response to 1% menthol was significantly lower than
      when menthol was tested first. After menthol, the subsequent response to CA was
      significantly weaker compared to the mean CA-evoked response when it was tested
      first. These results demonstrate mutual cross-desensitization between CA and
      menthol. The response to CA was enhanced following prior application of 10%
      ethanol (menthol vehicle). Prior application of menthol did not prevent the
      biphasic effect of 10% CA on cold-evoked responses, nor did prior application of
      CA prevent menthol enhancement of cold-evoked responses. Responses to noxious
      heat were unaffected by 10% CA and menthol regardless of the order of chemical
      presentation. These data indicate that superficial Vc neurons receive convergent
      input from primary afferents expressing TRPM8 and TRPA1. The mutual cross
      desensitization between CA and menthol, and differential modulation of cold- vs.
      heat-evoked responses, suggests a direct inhibition of TRPM8 and TRPA1 expressed
      in peripheral nerve endings by CA and menthol, respectively, rather than a
      central site of interaction.

PMID- 18060697
TI  - Effect of acupuncture on anxiety-like behavior during nicotine withdrawal and
      relevant mechanisms.
AB  - Acupuncture, likely the most well-known 'alternative' medical treatment, has been
      shown to have effects in several types of animal model of drug dependence,
      including nicotine addiction. We investigated the effect of acupuncture on
      anxiety-like behavior and corticotrophin-releasing factor (CRF) and neuropeptide
      Y (NPY) mRNA expression in the amygdala during nicotine withdrawal. Rats were
      given repeated nicotine injections (0.1mg/kg s.c., once daily for 7 days) or
      saline. Acupuncture groups were treated with acupuncture at acupoint HT7 or ST36
      during withdrawal. The anxiogenic response was measured at 72h after the
      termination of nicotine injection using an elevated plus maze. CRF and NPY mRNA
      levels were also evaluated using reverse transcription polymerase chain reaction
      (RT-PCR) analysis at this time. Rats undergoing nicotine withdrawal (NW) were
      less likely to explore the open arms of the plus maze compared with the saline
      treated controls. The percentage of open arm entries in the HT7 acupuncture
      group, but not in the ST36 acupuncture group, was significantly increased
      compared with the NW group. Consistent with this behavior, CRF mRNA levels in the
      NW group were increased compared with the control group. CRF mRNA levels in the
      HT7 acupuncture group were significantly decreased compared with the NW group.
      However, NPY mRNA levels were not different among the groups. These findings
      indicate that increases in CRF may be involved in the negative affect state
      associated with nicotine withdrawal and that acupuncture may attenuate anxiety
      like behavior following nicotine withdrawal by modulating CRF in the amygdala.

PMID- 18060698
TI  - Magnetic circular dichroism in electron energy loss spectrometry.
AB  - The measurement of circular dichroism in the electron microscope is a new,
      emerging method and, as such, it is subject to constant refinement and
      improvement. Different ways can be envisaged to record the signal. We present an
      overview of the key steps in the energy-loss magnetic chiral dichroism (EMCD)
      experiment as well as a detailed review of the methods used in the intrinsic way
      where the specimen is used as a beam splitter. Lateral resolution up to 20-30 nm
      can be achieved, and the use of convergent beam techniques leads to an improved
      S/N ratio. Dichroic effects are shown for Ni and Co single crystal; as a
      counterexample, measurements were carried also for a non-magnetic (Ti) sample,
      where no dichroic effect was found.

PMID- 18060699
TI  - STEM nanodiffraction technique for structural analysis of CoPt nanoparticles.
AB  - Studying the structure of nanoparticles as a function of their size requires a
      correlation between the image and the diffraction pattern of single
      nanoparticles. Nanobeam diffraction technique is generally used but requires long
      and tedious TEM investigations, particularly when nanoparticles are randomly
      oriented on an amorphous substrate. We bring a new development to this structural
      study by controlling the nanoprobe of the Bright and Dark Field STEM (BF/DF STEM)
      modes of the TEM. The particularity of our experiment is to make the STEM
      nanoprobe parallel (probe size 1 nm and convergence angle <1 mrad) using a fine
      tuning of the focal lengths of the microscope illumination lenses. The accurate
      control of the beam position offered by this technique allowed us to obtain
      diffraction patterns of many single nanoparticles selected in the digital STEM
      image. By means of this technique, we demonstrate size effects on the order
      disorder transition temperature in CoPt nanoparticles when their size is smaller
      than 3 nm.

PMID- 18060700
TI  - Prerequisites for a Cc/Cs-corrected ultrahigh-resolution TEM.
AB  - After the introduction of a corrector to compensate for the spherical aberration
      of a TEM and the acceptance of this new instrumentation for high-resolution CTEM
      (conventional transmission electron microscope) and STEM (scanning transmission
      electron microscope) by the electron microscopy community, a demand for even
      higher resolution far below 1A has emerged. As a consequence several projects
      around the world have been launched to make these new instruments available and
      to further push the resolution limits down toward fractions of 1A. For this
      purpose the so-called TEAM (transmission electron aberration-corrected
      microscope) has been initiated and is currently under development. With the
      present paper we give a detailed assessment of the stability required for the
      base instrument and the electric stability, the manufacturing precision, and
      feasible semi-automatic alignment procedures for a novel C(c)/C(s)-corrector in
      order to achieve aberration-free imaging with an information limit of 0.5A at an
      acceleration voltage of 200 kV according to the goals for the first TEAM
      instrument. This new aberration corrector, a so-called Achroplanat, in
      combination with a very stable high-resolution TEM leads to an imaging device
      with unprecedented resolving power and imaging properties.

PMID- 18060701
TI  - Warsaw adolescent alcohol use in a period of social change in Poland: cluster
      analyses of five consecutive surveys, 1988 to 2004.
AB  - This study aimed to analyze changes in patterns of alcohol use from 1988 to 2004
      amongst Polish (Warsaw) 15-year olds. Data were collected from 5 consecutive
      surveys, beginning in 1988 and conducted every four years. For each survey a
      comparable sampling approach, sample size (N >or =1461), procedures and
      instrument were used to ensure consistency of method across surveys. In 1988 a
      two-step cluster analysis was used to identify four distinct natural groups of
      drinkers "light", "heavier", "beer and wine" and "wine" drinkers. Between 1988
      and 1992 the percentage of teenage infrequent drinkers decreased and the rate of
      heavy drinkers increased. A group of students drinking only beer appeared, whilst
      the group of wine drinkers disappeared. A group of students who drank alcohol to
      get drunk appeared in 1996. Between 2000 and 2004 drinking of various kinds of
      alcoholic beverages became more frequent, as did vodka abuse. Increased
      consumption amongst girls was also observed. The results are interpreted in the
      context of social change and several hypothetical causes of gender differences
      are discussed.

PMID- 18060703
TI  - Late gastrointestinal morbidity after three-dimensional conformal radiation
      therapy for prostate cancer fades with time in contrast to genitourinary
      morbidity.
AB  - PURPOSE: To investigate the incidence, time course, and relation to irradiated
      volumes of late morbidity after three-dimensional conformal radiation therapy
      (RT) for prostate cancer. METHODS AND MATERIALS: From January 2000 to December
      2001, a total of 247 patients with prostate cancer received a target dose of 70
      Gy using conformal RT. Forty-eight patients (20%) received irradiation to the
      prostate only (Group P), 154 patients (62%) received irradiation to the prostate
      and seminal vesicles (Group PSV), and 45 patients (18%) received modified pelvic
      fields (Group MPF). Androgen deprivation was given to 86% of patients. Median
      follow-up was 62 months. Late gastrointestinal (GI) and genitourinary (GU)
      morbidity were recorded according to the Radiation Therapy Oncology Group scoring
      system. RESULTS: We observed 9%, 7%, and 25% Grade 2 or higher GI morbidity and
      36%, 30%, and 21% Grade 2 or higher GU morbidity in Groups P, PSV, and MPF,
      respectively. In multivariate analyses, age and treatment group were independent
      predictors for the incidence of late Grade 2 or higher GI morbidity, whereas age
      and urinary symptoms before treatment were independent predictors for late Grade
      2 or higher GU morbidity. Acute side effects predicted for late effects. The
      rectum dose-volume histogram parameters correlated with the incidence of late
      Grade 2 or higher GI morbidity, especially the fractional volume receiving more
      than 40-43 Gy. At 5 years of follow-up, the rate of Grade 2 late GI morbidity was
      only 1.4%, and Grade 2 or higher GU morbidity was 10.6%. CONCLUSIONS: The data
      presented here show that late GI morbidity after prostate RT is low and subsides
      with time.

PMID- 18060702
TI  - A survey of radiation-induced bronchiolitis obliterans organizing pneumonia
      syndrome after breast-conserving therapy in Japan.
AB  - PURPOSE: We observed a rare and unique occurrence of radiation-induced pulmonary
      injury outside the tangential field for early breast cancer treatment. The
      findings appeared to be idiopathic and were called radiation-induced
      bronchiolitis obliterans organizing pneumonia (BOOP) syndrome. We surveyed major
      hospitals in Japan to review their findings of radiation-induced BOOP, in
      particular the clinical and pictorial characteristics of the entity. METHODS AND
      MATERIALS: We reviewed surveys completed and returned by 20 institutions. The
      survey responses were based on a total of 37 cases of BOOP syndrome. We also
      reviewed X-ray and computed tomography scans provided by these institutions. We
      discussed the information derived from the questionnaire and analyzed patients'
      characteristics, methods used in the treatment of BOOP syndrome, and prognosis.
      RESULTS: The incidence of the radiation-induced BOOP syndrome was about 1.8% (37
      of 2,056). We did not find a relationship between the characteristics of patients
      and the occurrence of radiation-induced BOOP syndrome. The pulmonary findings
      were classified into four patterns on chest computed tomography scans.
      Progression of the pulmonary lesions observed on chest X-ray was classified into
      three patterns. Pneumonitis appeared within 6 months after radiotherapy was
      completed and disappeared within 6-12 months after its onset. At 5-year follow
      up, 2 patients had died, 1 of breast cancer and the other of interstitial
      pneumonitis, which seemed to be idiopathic and unrelated to the radiation-induced
      BOOP syndrome. CONCLUSIONS: Although the incidence of BOOP syndrome and its
      associated prognosis are not significant, the patients' clinical condition must
      be carefully followed.

PMID- 18060704
TI  - Maternally-administered lipopolysaccharide (LPS) increases tumor necrosis factor
      alpha in fetal liver and fetal brain: its suppression by low-dose LPS
      pretreatment.
AB  - Lipopolysaccharide (LPS) has been associated with adverse developmental outcome,
      including intra-uterine fetal death (IUFD), intra-uterine growth retardation
      (IUGR) and neurological injury. In the LPS model, tumor necrosis factor alpha
      (TNF-alpha) is the major mediator leading to IUFD, IUGR and neurological injury.
      In the present study, we investigated the effect of maternally-administered LPS
      on TNF-alpha in maternal serum, amniotic fluid, fetal liver and fetal brain. The
      timed pregnant mice were intraperitoneally (i.p.) injected with a single dose of
      LPS (500microg/kg) on gestational day 17. As expected, TNF-alpha was obviously
      increased in maternal serum and amniotic fluid in response to LPS. Although
      maternally-administered LPS also increased the level of TNF-alpha protein in
      fetal liver and brain, no significant difference in TNF-alpha mRNA level in fetal
      liver and brain was observed among different groups, suggesting that the
      increased TNF-alpha protein in fetal liver and brain may be transferred from
      either the maternal circulation or amniotic fluid or placenta. When the pregnant
      mice were pretreated with a low-dose LPS (10microg/kg, i.p.) at 4, 12, 24 or 48h
      before LPS (500microg/kg, i.p.), LPS-evoked TNF-alpha in maternal serum and
      amniotic fluid was significantly inhibited. Importantly, low-dose LPS
      pretreatment also greatly attenuated LPS-induced increases in TNF-alpha protein
      in fetal liver and fetal brain. Taken together, these results indicate that
      perinatal exposure to low-dose LPS induces a reduced sensitivity to subsequent
      LPS challenge.

PMID- 18060705
TI  - Effects of in utero and lactational exposure to endosulfan in prefrontal cortex
      of male rats.
AB  - The possible neurotoxic effects of the organochlorine pesticide endosulfan have
      been evaluated on male offspring rats exposed in utero and during lactation. Dams
      were treated with 0.61mg or 6.12mg endosulfan/(kgday) from the gestation
      beginning until the weaning. Male offspring rats were sacrificed at post-natal
      days (PND) 15, 30 and 60, and possible alterations in the content and metabolism
      of biogenic amines and amino acids were determined in prefrontal cortex using
      high-performance liquid chromatography (HPLC). Globally, endosulfan induced an
      increase in amino acid content in prefrontal cortex at PND 15 and PND 30.
      However, the levels of GABA at PND 15 and those of glutamine at PND 30 were not
      modified. At PND 60, a significant reduction in the content of GABA and taurine
      was observed, while the concentration of glutamate, aspartate and glutamine
      remained constant. Endosulfan did not modify norepinephrine and dopamine content,
      but serotonin concentration was increased at PND 30 and PND 60 and serotoninergic
      and dopaminergic metabolism was also modified. These results suggest that pre-
      and post-natal exposure to endosulfan affects biogenic amines and amino acids in
      prefrontal cortex, and those variations could be related to several alterations
      in the functions in which the prefrontal cortex is involved.

PMID- 18060706
TI  - Acute effect of intranasal estrogen on cerebral and cerebellar perfusion in
      postmenopausal women.
AB  - OBJECTIVES: Estrogen action in the brain influences many neurochemical processes.
      The aim of the study was to evaluate the acute effect of intranasal 17beta
      estradiol on cerebral and cerebellar perfusion in postmenopausal women. METHODS:
      The study group included 24 healthy postmenopausal women who had been in natural
      menopause for at least 1 year (mean age: 47.38+/-5.9 years). We conducted an
      experimental, randomized, placebo-controlled, cross-over, double-blind study.
      Cerebral and cerebellar perfusion was measured after placebo (saline serum
      physiologic) or intranasal 17beta-estradiol administration by Single Photon
      Emission Computed Tomography (SPECT) using technetium-99m-hexamethylpropylene
      amine oxime (Tc99m-HMPAO). Regions of interest (ROIs) were drawn manually.
      Cerebral and cerebellar perfusions were calculated for each ROI using average
      number of counts per pixel. Semiquantitative analysis was performed in bilateral
      frontal, temporal, parietal and occipital lobes, thalamus, putamen, hippocampus,
      amygdala, caudate nuclei, cerebellar region, anterior/posterior of cingulate
      gyrus and pons. RESULTS: After intranasal 17beta-estradiol administration, SPECT
      study revealed significant increases in cerebral and cerebellar perfusion
      compared to placebo measurements in all studied slices (p<0.05). There was a
      positive correlation between serum estrogen levels after 17beta-estradiol and
      cerebral and cerebellar perfusion. CONCLUSIONS: Administration of single dose
      intranasal 17beta-estradiol increases cerebral and cerebellar perfusions in
      healthy postmenopausal women.

PMID- 18060707
TI  - Suppression of lipopolysaccharide-induced of inducible nitric oxide synthase and
      cyclooxygenase-2 by Sanguis Draconis, a dragon's blood resin, in RAW 264.7 cells.
AB  - Sanguis Draconis (SD) is a kind of dragon's blood resin that is obtained from
      Daemomorops draco (Palmae). It is used in traditional medicine and has shown anti
      inflammatory activity in some diseases. In this study, we examined the effects of
      Sanguis Dranonis ethanol extract (SDEE) on LPS-induced inflammation using RAW
      264.7 cells. Our data indicated that SDEE inhibits LPS-stimulated NO, PGE2, IL-1
      beta and TNF-alpha release, and iNOS and COX-2 expression. Furthermore, SDEE
      suppressed the LPS-induced p65 expression of NF-kappa B, which was associated
      with the inhibition of I kappa B-alpha degradation. We also found that the
      expression of HO-1 was significantly increased in RAW 264.7 cells by SDEE. These
      results suggest among possibilities of anti-inflammation that SDEE inhibits the
      production of NO and PGE2 by the down-regulation of iNOS and COX-2 gene
      expression via the suppression of NF-kappaB (p65) activation. SDEE can induce HO
      1 over-expression in macrophage cells, which indicates that it may possess
      antioxidant properties. This result means that SEDD its anti-inflammatory effects
      in macrophages may be through a novel mechanism that involves the action of HO-1.
      Thus, SD could provide a potential therapeutic approach for inflammation
      associated disorders.

PMID- 18060708
TI  - Dragon's blood: botany, chemistry and therapeutic uses.
AB  - Dragon's blood is one of the renowned traditional medicines used in different
      cultures of world. It has got several therapeutic uses: haemostatic,
      antidiarrhetic, antiulcer, antimicrobial, antiviral, wound healing, antitumor,
      anti-inflammatory, antioxidant, etc. Besides these medicinal applications, it is
      used as a coloring material, varnish and also has got applications in folk magic.
      These red saps and resins are derived from a number of disparate taxa. Despite
      its wide uses, little research has been done to know about its true source,
      quality control and clinical applications. In this review, we have tried to
      overview different sources of Dragon's blood, its source wise chemical
      constituents and therapeutic uses. As well as, a little attempt has been done to
      review the techniques used for its quality control and safety.

PMID- 18060709
TI  - Pharmacokinetic comparisons of schizandrin after oral administration of
      schizandrin monomer, Fructus Schisandrae aqueous extract and Sheng-Mai-San to
      rats.
AB  - Sheng-Mai-San (SMS) is a famous traditional Chinese medicine (TCM) recipe,
      containing Radix Ginseng (Panax ginseng C.A. Mey., Araliaceae), Radix
      Ophiopogonis (Ophiopogon japonicus (Thunb.) Ker-Gawl., Liliaceae) and Fructus
      Schisandrae (Schisandra chinensis (Turcz.) Baill., Magnoliaceae), and has been
      used more than one thousand years. In this research, pharmacokinetics of one
      component of this TCM recipe was studied. Schizandrin is the main absorbed
      effective ingredient of Fructus Schisandrae and its pharmacokinetics were studied
      following oral administration of pure schizandrin, Fructus Schisandrae aqueous
      extract, and SMS decoction in rats with approximately the same dose of 5mg/kg. At
      different time points (0, 0.083, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12h)
      after administration, the concentrations of schizandrin in rat plasma were
      determined by LC-MS, and main pharmacokinetic parameters were estimated. It was
      found that both AUC0-tn and T1/2 of schizandrin in Fructus Schisandrae aqueous
      extract and in SMS decoction were increased significantly (p<0.05) comparing with
      that in monomer. The content assay also revealed that the concentrations of
      lignans would increase when SMS decocting, comparing with Fructus Schisandrae.
      These results indicate that some ingredients in SMS may increase the dissolution
      of schizandrin when decocting in vitro, and delay its elimination and enhance its
      bioavailability in rat.

PMID- 18060710
TI  - Further pharmacological studies on aqueous seed extract of Aframomum melegueta in
      rats.
AB  - This present study investigates the effect of an aqueous seed extract of
      Aframomum melegueta, on leukocytes migration and on phenylhydrazine-treated rat
      red blood cells (RBC). The effect of Aframomum melegueta on the number of white
      blood cells (WBC), in inflammatory exudates, was assessed by utilizing the
      granuloma air pouch model, for chronic inflammation in carrageenin-treated rats.
      The extract was tested for its anti-oxidant and membrane-stabilizing effects, in
      rat RBC exposed to phenylhydrazine. Aframomum melegueta was found to
      significantly reduce the number of WBC, in the fluid in a dose-related manner.
      The extract also produced significant inhibition of rat red blood cells lysis
      exposed to phenylhydrazine, which suggests a membrane-stabilizing effect. It
      further demonstrated a potent anti-oxidant activity, as it significantly reduced
      the levels of malonydialdehyde (MDA) formation in rat RBC exposed to
      phenylhydrazine. The results of this study, suggest that Aframomum melegueta
      possess membrane-stabilizing activity, along with anti-oxidant property and may
      also have a modifying effect, on the responses of WBC to tissue injury.

PMID- 18060711
TI  - Epithelial-myoepithelial carcinoma arising in the nasal cavity.
AB  - This study documents a case of an epithelial-myoepithelial carcinoma (EMC) in the
      left nasal cavity. A 70-year-old woman who presented with recurrent epistaxis of
      the left nasal nostril of 3 months duration was found to have a polypoid tumor in
      the left nasal cavity. A computed tomography (CT) scan revealed a tumor to occupy
      the left inferior and middle nasal cavity which had destroyed the inferior nasal
      turbinate, and a horizontal scan showed the tumor to occupy the middle and
      posterior nasal cavity. Since the tumor was connected to the lateral wall of the
      left nasal cavity with a narrow stalk, the tumor was excised by peeling the
      mucosa from the wall of the left nasal cavity. Based on the histological and
      immunohistochemical findings, the tumor was diagnosed to be an EMC. The follow-up
      at 12 months after the operation showed no evidence of recurrence.

PMID- 18060712
TI  - Enhanced resting-state brain activities in ADHD patients: a fMRI study.
AB  - Resting-state functional MRI (fMRI) could be an advantageous choice for clinical
      applications by virtue of its clinical convenience and non-invasiveness. Without
      explicit stimulus, resting-state brain activity patterns cannot be obtained using
      any model-driven method. In this study, we advanced a measure named resting-state
      activity index (RSAI) to evaluate the resting-state brain activities. Using RSAI,
      we first investigated the resting-state brain activity patterns in normal
      adolescents to test the validity of this RSAI measure. Then we compared the
      resting-state brain activity patterns of Attention deficit hyperactivity disorder
      (ADHD) patients to those of their matched controls. According to the resultant
      brain activity patterns, we suggest that RSAI could be an applicable measure to
      evaluate resting-state brain activities. As compared to the controls, the ADHD
      patients exhibited more significant resting-state activities in basic sensory and
      sensory-related cortices. This finding was in accordance with ADHD symptoms of
      inattention.

PMID- 18060713
TI  - [The incidence of the child psychic handicap in the department of Var in 2001
      from CDES files].
AB  - BACKGROUND: Thanks to an automated treatment of the medical information of the
      Departmental Commission of the Special Education in the Var, set up since 1999,
      under the responsibility of an epidemiologist doctor, it is possible to measure
      the incidence rates of the children recognized as been handicapped. METHODS: This
      study is the first one performed on the basis of good-quality and reliable
      medical and administrative informations. Moreover, this study has yielded
      thinking on the criteria of handicap definition and nomenclature to be used to
      define psychic deficiency. RESULTS: The occurrence rate of children recognized as
      handicapped by the Departmental Commission of the Var is 2.04%. The rate of
      children with a psychic deficiency recognized by the Commission is 1.25%. These
      rates are 2.5 times higher among boys than girls. Psychic deficiencies occurs
      mainly between five and nine years of age, at the entry to the primary school.
      The western part of the department displays rates of nevrotic, reactional,
      instrumental functions, and training disorders that are higher than those of the
      other geographical areas. For the eastern part of the department, the rates of
      psychoses, pathologies of the personality and evolutionary disorders are the
      highest. The distribution of declared pathologies probably reflects equipment of
      the medical sector of childpsychiatry and distribution of the liberal assumptions
      of responsibility. The geographical area of Draguignan is significantly under
      equipped with medico-social structures but is characterized by a high rate of
      children with a psychic handicap. CONCLUSION: The Law of February 11 2005 for
      chance and equal right, stipulates a counting of the people affected by handicap
      and the underlying pathologies, to define the ethiology of the handicap, to
      improve the accompaniment of those people and to develop actions aimed at
      reducing the incapacities and at the prevention of risks. It is within the
      Departmental houses of the handicapped person that the information systems will
      have to collect a minimum common set of standardized data to meet requirements of
      the Law of February 2005 and to take part in the planification of the means of
      medico-social establishment.

PMID- 18060714
TI  - Functional limitations and overweight among migrants in the Histoire de Vie study
      (Insee, 2003).
AB  - BACKGROUND: In France, epidemiological data on immigrant population are limited
      since characterization of immigrants is viewed as a sensitive issue. The Histoire
      de Vie survey has enabled the description of the association of immigration
      characteristics and two health indicators. METHODS: Health-related functional
      limitations and overweight status (BMI> or =25 kg/m(2)) were studied among 18 to
      64 years old using indirect age standardization. Immigration status was
      characterized in four different ways: via the migratory pathways of interviewees
      and their parents (French born to two French-born parents, second-generation,
      immigrated at the age of 15 or younger, immigrated at the age of 16 or older),
      citizenship (French by birth, French by naturalisation, non French), geographical
      origin (France, Europe, outside Europe) and language(s) spoken at home (French
      mother tongue, French for persons who do not have French as mother tongue, French
      and another language, another language). The analyses were conducted separately
      in men and in women and stratified by occupational status (upper and lower). For
      functional limitations, the analysis was repeated excluding participants whose
      limitations occurred before the age of 19, which was the average age of
      immigration, to assess a possible healthy migrant effect. RESULTS: Compared to
      French men born to two French parents, an increased rate of functional
      limitations was observed among men born in Europe and/or who had at least one
      parent born in Europe (SMR: 1.4; 95% CI: 1.06-1.81) and a reduced rate among
      participants born outside Europe or who had at least one parent born outside
      Europe (SMR: 0.63; 95% CI: 0.46-0.86); these differences remained when social
      status was taken into account. Among women, a tendency towards a lower rate of
      functional limitations was found in lower social status groups among those who
      immigrated as adults, among non French citizens and among non Europeans.
      Restricting the analysis to individuals free of limitations at the age of 19 did
      not suggest a healthier migrant effect. Among men, the risk of being overweight
      did not differ according to immigration characteristics. Women who immigrated in
      their adult life (SMR: 1.42; 95% CI: 1.18-1.74), who had foreign citizenship
      (SMR: 1.44; 95% CI: 1.18-1.74) and who still spoke their mother tongue at home
      (SMR: 1.53; 95%CI: 1.23-1.88) were more likely to be overweight than non migrant
      women. These results were observed in lower social groups but not in upper social
      groups. CONCLUSION: These results demonstrate a heterogeneous relationship
      between immigration status and health, according to age at immigration, gender
      and origin while the migrant second-generation appears quite close to the
      population born French to two French-born parents. Further studies are needed to
      provide data on a wider range of health indicators. In the future, health surveys
      should document detailed information to allow for a full characterisation of the
      migrant population.

PMID- 18060715
TI  - Assessment of three different software systems in the evaluation of dynamic MRI
      of the breast.
AB  - OBJECTIVE: The aim was to compare the diagnostic performance and handling of
      dynamic contrast-enhanced MRI of the breast with two commercial software
      solutions ("CADstream" and "3TP") and one self-developed software system
      ("Mammatool"). MATERIALS AND METHODS: Identical data sets of dynamic breast MRI
      from 21 patients were evaluated retrospectively with all three software systems.
      The exams were classified according to the BI-RADS classification. The number of
      lesions in the parametric mapping was compared to histology or follow-up of more
      than 2 years. In addition, 25 quality criteria were judged by 3 independent
      investigators with a score from 0 to 5. Statistical analysis was performed to
      document the quality ranking of the different software systems. RESULTS: There
      were 9 invasive carcinomas, one pure DCIS, one papilloma, one radial scar, three
      histologically proven changes due to mastopathy, one adenosis and two
      fibroadenomas. Additionally two patients with enhancing parenchyma followed with
      MRI for more than 3 years and one scar after breast conserving therapy were
      included. All malignant lesions were classified as BI-RADS 4 or 5 using all
      software systems and showed significant enhancement in the parametric mapping.
      "CADstream" showed the best score on subjective quality criteria. "3TP" showed
      the lowest number of false-positive results. "Mammatool" produced the lowest
      number of benign tissues indicated with parametric overlay. CONCLUSION: All three
      software programs tested were adequate for sensitive and efficient assessment of
      dynamic MRI of the breast. Improvements in specificity may be achievable.

PMID- 18060716
TI  - Quantitative correlation between (1)H MRS and dynamic contrast-enhanced MRI of
      human breast cancer.
AB  - Proton magnetic resonance spectroscopy ((1)H MRS) and dynamic contrast-enhanced
      (DCE) magnetic resonance imaging (MRI) provide functional information, including
      vascular volume, vascular permeability and choline (Cho) metabolism. In this
      study, we applied these two imaging modalities to quantitatively characterize 36
      malignant breast lesions in 32 patients and analyzed the correlation between
      them. Cho concentration was quantified by single-voxel (1)H MRS using water as an
      internal reference. The measured Cho levels ranged from 0.32 to 10.47 mmol/kg,
      consistent with previously reported values. In 25 mass-type lesions, the Cho
      concentration was significantly correlated with tumor size (r=.69, P<.0002). In
      addition, the Cho level was found to be significantly higher in lesions
      presenting as mass-type lesions compared to non-mass-type diffuse enhancements
      (P=.035). The enhancement kinetics from tissues covered within each MRS voxel
      were measured and analyzed with a two-compartmental model to obtain
      pharmacokinetic parameters K(trans) and k(ep). A significant correlation was
      found between the Cho level and the pharmacokinetic parameter k(ep) (r=.62,
      P<.0001), indicating that tissues with a high Cho level have higher wash-out
      rates in DCE MRI. The results suggest a correlation between Cho metabolism and
      angiogenesis activity, which might be explained by the association of Cho with
      cell replication and angiogenesis required to support tumor growth.

PMID- 18060717
TI  - Reproducibility of the quantitative assessment of cartilage morphology and
      trabecular bone structure with magnetic resonance imaging at 7 T.
AB  - To assess the reproducibility of quantitative measurements of cartilage
      morphology and trabecular bone structure of the knee at 7 T, high-resolution
      sagittal spoiled gradient-echo images and high-resolution axial fully refocused
      steady-state free-precession (SSFP) images from six healthy volunteers were
      acquired with a 7-T scanner. The subjects were repositioned between repeated
      scans to test the reproducibility of the measurements. The reproducibility of
      each measurement was evaluated using the coefficient(s) of variation (CV). The
      computed CV were 1.13% and 1.55% for cartilage thickness and cartilage volume,
      respectively, and were 2.86%, 1.07%, 2.27% and 3.30% for apparent bone volume
      over total volume fraction (app.BV/TV), apparent trabecular number (app.Tb.N),
      apparent trabecular separation (app.Tb.Sp) and apparent trabecular thickness
      (app.Tb.Th), respectively. The results demonstrate that quantitative assessment
      of cartilage morphology and trabecular bone structure is reproducible at 7 T and
      motivates future musculoskeletal applications seeking the high-field strength's
      superior signal-to-noise ratio.

PMID- 18060718
TI  - Comparison of T2 and LASER T2dagger image contrast in a rat model of acute
      cerebral ischemia.
AB  - Previous studies have shown that T2(dagger)-weighted magnetic resonance images
      acquired using localization by adiabatic selective refocusing (LASER) can provide
      early tissue contrast following ischemia, possibly due to alterations in
      microscopic susceptibility within the tissue. The purpose of this study was to
      make a direct in vivo comparison of T2-, T2(dagger)- and diffusion-weighted image
      contrast during acute ischemia. Acute middle cerebral artery (MCA) occlusion was
      attempted in 14 rats using a modified Tamura approach incorporating
      electrocoagulation of the left MCA. T2(dagger)-weighted LASER images (Echo Time
      [TE]=108 ms), T2-weighted Carr-Purcell-Meiboom-Gill (CPMG) images (TE=110 ms) and
      diffusion-weighted images (b value=105 s/mm(2)) were acquired at 4 T within 1.5 h
      of ischemia onset. Tissue contrast in the MCA territory was quantified for
      histologically verified ischemic tissue (n=6) and in sham controls (n=4).
      T2(dagger)-weighted LASER images demonstrated greater contrast compared to the T2
      weighted CPMG images, and more focal contrast compared to the diffusion-weighted
      images, suggesting different contrast mechanisms were involved.

PMID- 18060719
TI  - Simulation study on active noise control for a 4-T MRI scanner.
AB  - The purpose of this work is to study computationally the possibility of the
      application of a hybrid active noise control technique for magnetic resonance
      imaging (MRI) acoustic noise reduction. A hybrid control system combined with
      both feedforward and feedback loops embedded is proposed for potential
      application on active MRI noise reduction. A set of computational simulation
      studies were performed. Sets of MRI acoustic noise emissions measured at the
      patient's left ear location were recorded and used in the simulation study. By
      comparing three different control systems, namely, the feedback, the feedforward
      and the hybrid control, our results revealed that the hybrid control system is
      the most effective. The hybrid control system achieved approximately a 20-dB
      reduction at the principal frequency component. We concluded that the proposed
      hybrid active control scheme could have a potential application for MRI scanner
      noise reduction.

PMID- 18060720
TI  - Effects of spatial smoothing on fMRI group inferences.
AB  - The analysis of functional magnetic resonance imaging (fMRI) data involves
      multiple stages of data pre-processing before the activation can be statistically
      detected. Spatial smoothing is a very common pre-processing step in the analysis
      of functional brain imaging data. This study presents a broad perspective on the
      influence of spatial smoothing on fMRI group activation results. The data
      obtained from 20 volunteers during a visual oddball task were used for this
      study. Spatial smoothing using an isotropic gaussian filter kernel with full
      width at half maximum (FWHM) sizes 2 to 30 mm with a step of 2 mm was applied in
      two levels - smoothing of fMRI data and/or smoothing of single-subject contrast
      files prior to general linear model random-effects group analysis generating
      statistical parametric maps. Five regions of interest were defined, and several
      parameters (coordinates of nearest local maxima, t value, corrected threshold,
      effect size, residual values, etc.) were evaluated to examine the effects of
      spatial smoothing. The optimal filter size for group analysis is discussed
      according to various criteria. For our experiment, the optimal FWHM is about 8
      mm. We can conclude that for robust experiments and an adequate number of
      subjects in the study, the optimal FWHM for single-subject inference is similar
      to that for group inference (about 8 mm, according to spatial resolution). For
      less robust experiments and fewer subjects in the study, a higher FWHM would be
      optimal for group inference than for single-subject inferences.

PMID- 18060721
TI  - Model-free arterial spin labelling for cerebral blood flow quantification:
      introduction of regional arterial input functions identified by factor analysis.
AB  - PURPOSE: To identify regional arterial input functions (AIFs) using factor
      analysis of dynamic studies (FADS) when quantification of perfusion is performed
      using model-free arterial spin labelling. MATERIAL AND METHODS: Five healthy
      volunteers and one patient were examined on a 3-T Philips unit using quantitative
      STAR labelling of arterial regions (QUASAR). Two sets of images were retrieved,
      one where the arterial signal had been crushed and another where it was retained.
      FADS was applied to the arterial signal curves to acquire the AIFs. Perfusion
      maps were obtained using block-circulant SVD deconvolution and regional AIFs
      obtained by FADS. In the volunteers, the ASL experiment was repeated within 24 h.
      The patient was also examined using dynamic susceptibility contrast MRI. RESULTS:
      In the healthy volunteers, CBF was 64+/-10 ml/[min 100 g] (mean+/-S.D.) in GM and
      24+/-4 ml/[min 100 g] in WM, while the mean aBV was 0.94% in GM and 0.25% in WM.
      DISCUSSION: Good CBF image quality and reasonable quantitative CBF values were
      obtained using the combined QUASAR/FADS technique. We conclude that FADS may be a
      useful supplement in the evaluation of ASL data using QUASAR.

PMID- 18060722
TI  - Thioredoxin peroxidase from Echinococcus granulosus: a candidate to extend the
      antigenic panel for the immunodiagnosis of human cystic echinococcosis.
AB  - The currently available tests for the diagnosis of cystic echinococcosis (CE),
      enzyme-linked immunosorbent assay (ELISA), and immunoblotting (IB) lack
      sensitivity and specificity, and antigen panels need standardizing. By screening
      an Echinococcus granulosus cDNA library with IgG1 from patients with CE, we
      identified E. granulosus thioredoxin peroxidase (EgTPx). Although IB and ELISA
      achieved the same specificity (92%), ELISA showed higher sensitivity than IB (83%
      versus 42%) in determining total immunoglobulin G (IgG) specific to EgTPx in CE
      sera. The percentage of total IgG- and IgG1-positive sera in ELISA was equally
      distributed in patients with active, transitional, and inactive disease.
      Conversely, the percentages of IgG4-positive sera were significantly higher in
      sera from patients with active than inactive disease (P = 0.03). Our data suggest
      that adding this highly specific recombinant antigen to the standard diagnostic
      panel of antigens used in ELISA would increase diagnostic sensitivity. Antibodies
      specific to EgTPx are of potential interest in the host-parasite relationship.

PMID- 18060723
TI  - Performance of Binax NOW Flu A and B and direct fluorescent assay in comparison
      with a composite of viral culture or reverse transcription polymerase chain
      reaction for detection of influenza infection during the 2006 to 2007 season.
AB  - The Binax NOW Flu A and Flu B (Binax NOW), direct fluorescent assay (DFA), and
      viral culture were evaluated and compared with a composite of viral culture or
      reverse transcription polymerase chain reaction (RT-PCR). Participants with
      medically attended acute respiratory illness were identified through active
      surveillance during the 2006 to 2007 season, and consenting individuals (n=932)
      were tested for influenza by culture and RT-PCR. Physicians ordered a rapid
      antigen test (Binax NOW [n=73] or DFA [n=70]) according to their clinical
      judgment. The Binax NOW detected 11 of 18 influenza infections (sensitivity, 61%;
      95% confidence interval [CI], 36-83%), whereas DFA detected 17 of 21 influenza
      infections (sensitivity 81%, 95% CI, 58-95%). Compared with culture/RT-PCR,
      specificity of both Binax NOW and DFA was 100%. During the 2006 to 2007 influenza
      season, DFA and Binax NOW demonstrated high specificity but failed to identify a
      substantial proportion of influenza infections.

PMID- 18060724
TI  - A new 16S rDNA-RFLP method for the discrimination of the accepted species of
      Arcobacter.
AB  - The genus Arcobacter that includes some species of clinical interest has been
      recently enlarged with the addition of several new species. The available
      molecular techniques for the characterization of Arcobacter spp. are unable to
      identify all the species included in this genus. We have developed a 16S rDNA
      RFLP method able to separate the currently accepted 6 species of Arcobacter,
      including the 2 hybridization groups of Arcobacter cryaerophilus. The method
      based on the use of a pair of primers and of the endonuclease MseI has been
      validated using 12 reference strains (including the type strains) and 75 fresh
      isolates. All isolates tested produced species-specific RFLP patterns. This easy
      to-perform method allows a fast and reliable recognition of the members of this
      complex genus.

PMID- 18060725
TI  - Prospective evaluation of virulence factors of enterococci isolated from patients
      with peritonitis: impact on outcome.
AB  - The objective of this study was to evaluate the prevalence of 4 virulence factors
      (VFs) of enterococci (cytolysin [cyl], gelatinase [gel], aggregation substance
      [agg], and enterococcal surface protein [esp]) and their relationship to outcome
      in patients with generalized peritonitis in a prospective cohort study. VF
      expression in each strain was assessed by polymerase chain reaction assay with
      specific primers. Outcome of the patients was recorded. Ninety-nine strains of
      Enterococcus were obtained from the peritoneal fluid of 81 patients. Fifty-eight
      patients had at least 1 strain bearing [cyl] (13.1% of the strains), [gel] (50.5%
      of the strains), [agg] (40.4% of the strains), and [esp] (34.3% of the strains).
      The presence of VF of Enterococcus was independently associated with mortality:
      odds ratio, 5.5; 95% confidence interval, 1.3-28.1. In conclusion, VF accounted
      for 72% of the patients with enterococci isolated from the peritoneal fluid and
      was independently associated with mortality in severe peritonitis.

PMID- 18060726
TI  - Aortic reconstruction with femoral-popliteal vein: graft stenosis incidence, risk
      and reintervention.
AB  - BACKGROUND: Management using femoral-popliteal vein (FPV) of aortic graft
      infections, failing aortofemoral bypass, and aortoiliac occlusive disease in
      young patients with a small aorta is now an accepted therapeutic method and is
      performed frequently at our institution. A high reintervention rate for FPV graft
      stenosis has recently been reported. The purpose of this study was to determine
      the incidence of FPV graft failure due to stenosis after neoaortoiliac system
      (NAIS) reconstruction, and to identify risk factors for this complication.
      METHODS: A review was performed of 240 patients who underwent NAIS reconstruction
      at our institution between January 1991 and December 2005. All patients were
      entered into a prospective database and were evaluated for the incidence of vein
      graft stenosis requiring reintervention, risk factors for stenosis, and the rate
      and type of reintervention required to assist patency. Patients with occlusion
      are evaluated and reported, but excluded from detailed analysis. Risk factors
      assessed included gender, operative features, FPV size (diameter), smoking
      history, and medical comorbidities. RESULTS: Of the 240 NAIS procedures performed
      during this time period, 11 (4.6%) patients have required 12 graft revisions (one
      patient required a second intervention) for stenosis using open and endovascular
      techniques. Over the same time period, graft occlusion occurred in nine patients
      (3.8%). This provided a primary patency at 2 and 5 years of 87% and 82%, and an
      assisted primary patency rate of 96% and 94%. Mean time to revision was 23.5
      months (range 5.5 to 83.5 months). Median FPV graft size in the nonrevised
      patients was 7.8 mm (range 4.0 to 11.4 mm), and 6.4 mm (range 4.7 to 8.7 mm) in
      the revised group (P = .006). Survival analysis revealed small vein graft size
      (<7.2 mm), coronary artery disease (CAD), and extensive smoking history as
      independent predictors of time to stenosis (P = .002, .02, .01, respectively),
      with multivariable analysis confirming these results (P = .002, .06, .012).
      Patients with CAD combined with small graft size were found to be at especially
      high risk for stenosis, with 8/36 (22.2%) requiring revision vs 3/184 (1.6%) of
      patients without both factors (P < .0001). CONCLUSIONS: FPV graft stenosis
      requiring revision after NAIS reconstruction is uncommon. Risk factors for
      stenosis include small graft size, history of CAD, and smoking. All patients
      merit aggressive counseling for smoking cessation, and patients exhibiting
      multiple risk factors should undergo close postoperative surveillance for graft
      stenosis.

PMID- 18060727
TI  - Transcervical carotid stenting with flow reversal is safe in octogenarians: a
      preliminary safety study.
AB  - BACKGROUND: The use of carotid stenting in octogenarian patients is
      controversial; some authors consider this population at high risk for the
      procedure. Anatomic vascular complexity may be an important reason for the high
      reported rates of periprocedural thromboembolic complications. Transcervical
      carotid angioplasty and stenting (TCS) with flow reversal avoids aortic arch
      instrumentation. In this study, we analyzed our experience with TCS in
      octogenarian patients and compared the results with those of carotid
      endarterectomy (CEA) in the same age group in terms of safety. METHODS: The study
      included 81 patients, > or =80 years, a retrospective cohort of 45 consecutive
      patients treated with CEA (January 2002 to January 2005), and a prospective
      cohort of 36 consecutive patients treated with TCS with protective flow reversal
      (January 2005 to January 2007). Patients were considered symptomatic according to
      the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.
      Stenting indication was established on the SAPPHIRE criteria. General anesthesia
      was used in patients undergoing CEA, and local anesthesia in those receiving TCS.
      Primary endpoints were: stroke, death, or acute myocardial infarction within 30
      days. Secondary endpoints were peripheral nerve paralysis and cervical hematoma.
      Statistical significance for between-group differences was assessed by Pearson
      chi(2) or Fisher exact test, and Student t test. A P value of <.05 was considered
      statistically significant. Follow-up was limited to 30 days. RESULTS: Baseline
      epidemiological characteristics and revascularization indications were similar
      between both groups. Mean age was significantly higher in the TCS group (83.5 +/-
      3.35) than the CEA group (81.7 +/- 1.55) (P = .004). Percentage of symptomatic
      lesions was similar: 30.6% in TCS vs 44.4% in CEA (P = .2). Comorbid conditions
      (respiratory or cardiac) were more frequent in TCS group (61.6% vs 26.6%; P =
      .002). There were no significant differences between groups for the primary
      endpoints: 4.4% (one stroke, one acute myocardial infarction) for CEA vs 0% for
      TCS (P = .5). Among CEA patients, there were two peripheral nerve palsies (4.4%)
      and one cervical hematoma (2.2%); there were no such complications with TCS (P =
      .5 and P = 1, respectively). In one asymptomatic TCS patient, Doppler study at 24
      hours following the procedure showed a common carotid artery dissection, which
      was treated by a common carotid to internal carotid bypass. CONCLUSIONS: In this
      preliminary experience, transcervical carotid angioplasty and stenting with flow
      reversal for cerebral protection was as safe at short term as carotid
      endarterectomy in octogenarian patients, who additionally had considerable
      comorbidity; thus, it may be possible to extend the indications for carotid
      revascularization in this population. Studies in larger patient series are
      required to confirm the trends observed in this study.

PMID- 18060729
TI  - Guidelines for hospital privileges in vascular and endovascular surgery:
      recommendations of the Society for Vascular Surgery.
AB  - The Clinical Practice Council of the Society for Vascular Surgery (SVS) was
      charged with providing an updated consensus on guidelines for hospital privileges
      in vascular and endovascular surgery. One compelling reason to update these
      recommendations is that vascular surgery as a specialty has continued to evolve
      with a significant shift towards endovascular therapies. The Society for Vascular
      Surgery is making the following four recommendations concerning guidelines for
      hospital privileges for vascular and endovascular surgery. First, anyone applying
      for new hospital privileges to perform vascular surgery should have completed an
      Accreditation Council for Graduate Medical-accredited vascular surgery residency
      and should obtain American Board of Surgery certification in vascular surgery
      within 3 years of completion of their training. Second, we reaffirm and provide
      updated recommendations concerning previous established guidelines for peripheral
      endovascular procedures, thoracic and abdominal aortic endograft replacements,
      and carotid artery balloon angioplasty and stenting for trainees and already
      credentialed physicians who are adding these new procedures to their hospital
      credentials. Third, we endorse the Residency Review Committee for Surgery
      recommendations regarding open and endovascular cases during vascular residency
      training. Fourth, we endorse the Inter-societal Commission for Accreditation of
      Vascular Laboratories (ICAVL) recommendations for noninvasive vascular laboratory
      interpretations and examinations to become a registered physician in vascular
      interpretation (RPVI) or a registered vascular technologist (RVT).

PMID- 18060730
TI  - Peak wall stress measurement in elective and acute abdominal aortic aneurysms.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) rupture occurs when wall stress
      exceeds wall strength. Engineering principles suggest that aneurysm diameter is
      only one aspect of its geometry that influences wall stress. Finite element
      analysis considers the complete geometry and determines wall stresses throughout
      the structure. This article investigates the interoperator and intraoperator
      reliability of finite element analysis in the calculation of peak wall stress
      (PWS) in AAA and examines the variation in PWS in elective and acute AAAs.
      METHOD: Full ethics and institutional approval was obtained. The study recruited
      70 patients (30 acute, 40 elective) with an infrarenal AAA. Computed tomography
      (CT) images were obtained of the AAA from the renal vessels to the aortic
      bifurcation. Manual edge extraction, three-dimensional reconstruction, and
      blinded finite element analysis were performed to ascertain location and value of
      PWS. Ten CT data sets were analyzed by four different operators to ascertain
      interoperator reliability and by one operator twice to ascertain intraoperator
      reliability. An intraclass correlation coefficient was obtained. The Mann-Whitney
      U test and independent samples t test compared groups for statistical
      significance. RESULTS: The intraclass correlation coefficient was 0.71 for
      interoperator reliability and 0.84 for intraoperator reliability. There was no
      statistically significant difference in the mean (SD) maximal AAA diameter
      between elective (6.47 [1.30] cm) and acute (7.08 [1.39] cm) patients (P = .073).
      The difference in PWS between elective (0.67 [0.30] MPa) and acute (1.11 [0.51]
      MPa) patients (P = .008) was statistically significant, however. CONCLUSION:
      Interoperator and intraoperator reliability in the derivation of PWS is
      acceptable. PWS, but not maximal diameter, was significantly higher in acute AAAs
      than in elective AAAs.

PMID- 18060731
TI  - Open abdominal aortic aneurysm repair in octogenarians before and after the
      adoption of endovascular grafting procedures.
AB  - OBJECTIVE: This study evaluated (1) elective open abdominal aortic aneurysm
      repair (OAR) in patients aged > or =80 years before and after stent graft devices
      for endovascular aneurysm repair (EVAR) became commercially available and (2) the
      effect on perioperative (30-day) outcome of the anatomic constraints that led to
      EVAR being excluded for many of them. METHODS: A review was conducted on the
      records of 111 patients aged > or =80 years who underwent elective OAR during a
      14-year period at the University of Padua School of Medicine. Patients were
      separated into two groups: group 1 (n = 65) had OAR before and group 2 (n = 46)
      after an EVAR program was adopted at the medical school in mid-2000.
      Perioperative death and morbidity, location of proximal aortic clamp, management
      of the left renal vein, associated iliac aneurysmal or occlusive diseases, the
      type of surgical reconstruction, operating time, and lengths of stay in the
      intensive care unit and the hospital were recorded. All the data were compared
      between the two groups. RESULTS: Retroperitoneal approach, suprarenal clamping,
      left renal vein division, and longer operating room time were statistically more
      common in group 2 (36.9% vs 12.3%, P = .002; 15.2% vs 3.1%, P = .032; 23.9% vs
      7.7%, P = .026; and 117 +/- 8 min vs 95 +/-7 min, P < .001, respectively).
      Although group 2 had significantly more iliac aneurysms (52.1% vs 32.3%; P =
      .036), the number of bifurcated reconstructions was comparable. The overall
      perioperative mortality rate was 1.8% (2 of 111), and the figures for groups 1
      and 2 were comparable (3.1% vs 0%; P = .510). No deaths were cardiac related.
      Group 2 had a significantly higher incidence of kidney failure (8.7% vs 0%; P =
      .027). Kaplan-Meier analysis showed an overall 3-, 5-, and 10-year survival rate
      of 80.6%, 67.2%, and 59.4%, respectively, with a 3- and 5-year survival rate
      comparable between groups 1 and 2 (77.8% and 66.7% vs 87.8% and 45.8%,
      respectively; log-rank test, P = .921). CONCLUSIONS: Octogenarians can tolerate
      OAR with acceptable rates of perioperative mortality and morbidity. Although the
      complexity of OAR has increased significantly in the era of EVAR, the
      perioperative outcome has not changed.

PMID- 18060732
TI  - Changes in inferior vena cava filter placement over the past decade at a large
      community-based academic health center.
AB  - OBJECTIVE: A significant increase in the frequency of inferior vena cava (IVC)
      filter placement at our large community-based academic health center led us to
      evaluate changes in indications, devices, and providers over the past decade.
      METHODS: A single-center retrospective review of all filter placements was
      performed comparing 76 patients in 1995 with 470 patients in 2005. Demographic
      data, provider data, filter type, and indications for placement were tabulated.
      Complications, follow-up evaluation, filter removal, and patient outcomes were
      examined. RESULTS: There was a greater than sixfold increase in the number of
      filters placed in 2005 vs 1995. There were no significant differences in patient
      demographics or the extent of venous thromboembolic (VTE) disease during this
      period except for an increase in median age. Filter placement by interventional
      radiologists remained approximately 50% of the total whereas placement by
      vascular/trauma surgeons increased to 24% and placement by cardiologists
      decreased to 29% (P < .001). In 2005, a smaller percentage of filters were placed
      for absolute indications, while filter placements for relative and prophylactic
      indications increased over the same time period, especially among cardiologists
      (P = .02). Potentially retrievable filters are increasingly being used for
      prophylaxis; however, only 2.4% were retrieved. An increasing number of filters
      were placed in patients with only infrapopliteal deep venous thrombosis (P =
      .07). A shift was seen to lower profile and removable filter types. Long-term
      patient follow-up showed little change in disease progression or in morbidity and
      mortality of filter insertion. CONCLUSIONS: Technological and practice pattern
      changes have led to an increase in filters inserted by vascular and trauma
      surgeons in the operating room and intensive care units. Increased diagnosis of
      VTE disease and newer low profile delivery systems in patients may also have
      contributed to the significant increase in filter placement. A shift in
      indications for placement from absolute toward relative indications and
      prophylaxis is evident over time and across providers, indicating the need for
      consensus development of appropriate criteria.

PMID- 18060733
TI  - The value of quality of life and health status measurements in the evaluation of
      the well-being of breast cancer survivors.
AB  - BACKGROUND: Quality of life (QoL) in breast cancer survivors has become
      increasingly important. However, QoL is often assessed using a questionnaire
      meant to assess health status (HS). In this study the differences in outcomes
      between a HS and QoL questionnaire are shown and the correlation between both
      questionnaires is assessed. METHODS: From the 140 breast cancer survivors that
      participated in the study, 68 received breast conserving therapy (BCT) and 72
      were treated with mastectomy (MTC). HS was measured using the RAND-36 and QoL was
      assessed with the WHOQOL-100. Scores were compared with healthy reference
      populations. RESULTS: The scores on QoL in both treatment groups were comparable
      to those of healthy women. HS scores showed lower physical functioning and
      general health perceptions for the MTC women. Pearson correlations between both
      questionnaires ranged between 0.19 and 0.75. Thus, the results of both
      questionnaires were not interchangeable. CONCLUSION: A HS questionnaire reflects
      functional impairments and reveals different areas of concern compared with a QoL
      questionnaire. The latter reflects the (dis)satisfaction of a patient and this
      seems not to mirror the functional limitations. Assessment of both objective
      functioning and subjective appraisal of functioning will result in treatment
      suggestions that meet the patients needs.

PMID- 18060734
TI  - [The unfinished story of the ringworm children: irradiation for Tinea capitis].

PMID- 18060735
TI  - Role of Ca2+-binding motif in cytotoxicity induced by Clostridium perfringens
      iota-toxin.
AB  - Clostridium perfringens iota-toxin is a binary toxin composed of an enzymatic
      component (Ia) and a binding component (Ib). We investigated the role of the
      conserved Ca(2+)-binding motif of Ib in the cytotoxicity of iota-toxin. The
      cytotoxicity of iota-toxin increased with an increase in the concentration of
      extracellular Ca(2+). A surface plasmon resonance analysis showed that the
      binding of Ia to the oligomer of Ib is dependent on the concentration of Ca(2+).
      However, the addition of Ca(2+) had no effect on the binding of (125)I-labeled Ib
      to the cells. We replaced Asp-8, -10, and -12 in the Ca(2+)-binding motif of Ib
      with alanine. D8A, D10A, and D12A bound to the cell and formed an oligomer at
      about half of the wild-type Ib. The cytotoxicity of Ib variants in the presence
      of Ia was about 500-fold less than that of wild-type Ib. Immunofluorescence study
      showed that these variants were internalized in the early endosomes like wild
      type Ib. However, wild-type Ib-induced internalization of Ia in the cells, but
      these variants did not. The result indicates that the conserved Ca(2+)-binding
      motif in the N-terminal region of Ib plays a role in the interaction of Ib with
      Ia in the presence of Ca(2+).

PMID- 18060736
TI  - Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation
      and developmental disabilities.
AB  - We have identified disruptions in the dedicator of cytokinesis 8 gene, DOCK8, in
      two unrelated patients with mental retardation (MR). In one patient, a male with
      MR and no speech, we mapped a genomic deletion of approximately 230 kb in
      subtelomeric 9p. In the second patient, a female with mental retardation and
      ectodermal dysplasia and a balanced translocation, t(X;9) (q13.1;p24), we mapped
      the 9p24 breakpoint to a region overlapping with the centromeric end of the 230
      kb subtelomeric deletion. We characterized the DOCK8 gene from the critical 9p
      deletion region and determined that the longest isoform of the DOCK8 gene is
      truncated in both patients. Furthermore, the DOCK8 gene is expressed in several
      human tissues, including adult and fetal brain. Recently, a role for DOCK8 in
      processes that affect the organization of filamentous actin has been suggested.
      Several genes influencing the actin cytoskeleton have been implicated in human
      cognitive function and thus a possibility exists that the rare mutations in the
      DOCK8 gene may contribute to some cases of autosomal dominant mental retardation.

PMID- 18060737
TI  - Altered myocardial gene expression reveals possible maladaptive processes in
      heterozygous and homozygous cardiac myosin-binding protein C knockout mice.
AB  - Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease
      characterized by left ventricular hypertrophy (LVH) predominantly affecting the
      interventricular septum. Cardiac myosin-binding protein C (cMyBP-C) mutations are
      common causes of FHC. Gene expression profiling was performed in left ventricles
      of 9-week-old wild-type mice, heterozygous cMyBP-C KO mice displaying asymmetric
      septal hypertrophy, and homozygous mice developing eccentric LVH. Knocking out
      one or two cMyBP-C genes leads primarily to gene expression changes indicating an
      increased energy demand, activation of the JNK and p38 parts of the MAPK pathway
      and deactivation of the ERK part, and induction of apoptosis. Altered gene
      expression for processes related to cardiac structure, contractile proteins, and
      protein turnover was also identified. Many of the changes were more pronounced in
      the homozygous KO mice. These alterations point to physiological and pathological
      adaptations in the prehypertrophic heterozygous KO mice and the hypertrophic
      homozygous mice.

PMID- 18060738
TI  - The ascent of cat breeds: genetic evaluations of breeds and worldwide random-bred
      populations.
AB  - The diaspora of the modern cat was traced with microsatellite markers from the
      presumed site of domestication to distant regions of the world. Genetic data were
      derived from over 1100 individuals, representing 17 random-bred populations from
      five continents and 22 breeds. The Mediterranean was reconfirmed to be the
      probable site of domestication. Genetic diversity has remained broad throughout
      the world, with distinct genetic clustering in the Mediterranean basin,
      Europe/America, Asia and Africa. However, Asian cats appeared to have separated
      early and expanded in relative isolation. Most breeds were derived from
      indigenous cats of their purported regions of origin. However, the Persian and
      Japanese bobtail were more aligned with European/American than with Mediterranean
      basin or Asian clusters. Three recently derived breeds were not distinct from
      their parental breeds of origin. Pure breeding was associated with a loss of
      genetic diversity; however, this loss did not correlate with breed popularity or
      age.

PMID- 18060739
TI  - Analysis of PKD1 for genomic deletion by multiplex ligation-dependent probe
      assay: absence of hot spots.
AB  - Autosomal dominant polycystic kidney disease is largely due to mutations in PKD1.
      PKD1 has an unusual genomic structure, including a 2.5-kb polypyrimidine sequence
      in intron 21, which has been postulated to lead to a high rate of spontaneous
      genomic mutation events. In addition, the majority of the gene is duplicated
      three to six times at 97-99% identity elsewhere in the genome. To identify
      genomic mutations in PKD1, we developed a multiplex ligation-dependent probe
      assay (MLPA) in which sites of variation between PKD1 and its copies were
      positioned at the ligation sites of the MLPA probe sets. Thirteen probe sets
      covered PKD1 exons 2 through 46, at an average spacing of 2.5 kb. Analysis of 27
      independent PKD patient samples showed no evidence for genomic deletions confined
      to PKD1. Analysis of 15 tuberous sclerosis patient samples in which deletions in
      TSC2 extended into PKD1 showed no evidence of clustering of breakpoints near the
      polypyrimidine tract.

PMID- 18060740
TI  - Influence of singing activity, age, and sex on voice performance parameters, on
      subjects' perception and use of their voice in childhood and adolescence.
AB  - The aim of the study was to investigate the extent to which regular singing
      activity and voice training in children and adolescents enhance their voice
      performance parameters and their perception of their own voice and the extent to
      which their voice control is improved. At the same time, additional effects of
      age and sex were also taken into account. We investigated 183 children and
      adolescents between 6 and 19 years of age (mean age: 13.5 years) and assigned
      them to groups with different levels of voice strain and training with voice
      specialists. This was done on the basis of a classification of singing activity
      which we developed ourselves. We measured the voice parameters, and all of the
      test subjects were asked to appraise their perception and conscious control of
      their voices based on a questionnaire comprising 21 items. The higher the degree
      of vocal strain (taking regularity and organization of singing into
      consideration) and voice training, the more the perception and conscious control
      of the voice. Furthermore, the more intense the voice training, the wider the
      voice range becomes; the stronger the vocal strain, the better the capacity for
      messa di voce. On the other hand, the maximum duration of sustained phonation
      unexpectedly decreased, which we attribute to methodological reasons. Older
      children evince more differentiated perception of the sound of their own voices
      and imitate other voices more frequently. Boys show better values than girls as
      far as maximum voice intensity, maximum duration of phonation, and capacity for
      messa di voce are concerned. Boys also control their voices more consciously than
      girls. The results underscore the positive effects of regular singing and
      individual voice training on voice performance, sound perception, and conscious
      control of the voice. These results should encourage parents and pedagogues to
      provide opportunities for regular (organized) singing and voice training for as
      many children as possible. Moreover, age and gender have additional effects which
      should be taken into account in phoniatric and voice pedagogical counseling.

PMID- 18060741
TI  - Formyl peptide receptor-mediated ERK1/2 activation occurs through G(i) and is not
      dependent on beta-arrestin1/2.
AB  - Formyl peptide receptor (FPR) and C5a receptor (C5aR) are chemoattractant G
      protein-coupled receptors (GPCRs) involved in the innate immune response against
      bacterial infections and tissue injury. Like other GPCRs, they recruit beta
      arrestin1/2 to the plasma membrane and activate the extracellular signal
      regulated kinases 1 and 2 (ERK1/2). Previous studies with several GPCRs have
      suggested that beta-arrestins play an important role as signal transducers by
      scaffolding signaling molecules such as ERK1/2. This function of the beta
      arrestins was not discovered until several years after their role in
      desensitization and endocytosis had been reported. In this study, we investigated
      the role of the beta-arrestins in the activation of ERK1/2 and receptor
      endocytosis. We took advantage of previously described mutants of FPR that have
      defects in G(i) coupling or beta-arrestin recruitment. The results obtained with
      the mutant FPRs, as well as experiments using an inhibitor of G(i) and cells
      overexpressing beta-arrestin2, showed that activation of ERK1/2 takes place
      through G(i) and is not affected by beta-arrestins. However, overexpression of
      beta-arrestin2 does enhance FPR sequestration from the cell surface, suggesting a
      role in desensitization, as shown for many other GPCRs. Experiments with CHO C5aR
      cells showed similar sensitivity to the G(i) inhibitor as CHO FPR cells,
      suggesting that the predominant activation of ERK1/2 through G protein may be a
      common characteristic among chemoattractant receptors.

PMID- 18060742
TI  - A new imaging modality for intraoperative evaluation of sinus floor augmentation.
AB  - The aim of this report was to demonstrate the practicability of a new imaging
      modality, which allows three-dimensional intraoperative imaging and verification
      of bone-graft position, and to compare it to the currently available imaging
      systems. The ARCADIS Orbic 3D, a C-arm-based cone-beam computed tomography
      scanner developed for intraoperative imaging, was used to examine a previously
      augmented sinus floor, in order to verify the height and width of the
      augmentation and to determine whether any of the autogenous and synthetic bone
      substitute mixture had penetrated the sinus membrane. Visualization of the entire
      sinus was possible with the aid of multiplanar reconstructions. Data acquisition
      and processing took 5 min.

PMID- 18060743
TI  - Immediate impact of electroconvulsive therapy on cardiac autonomic function in
      schizophrenia: a preliminary study.

PMID- 18060745
TI  - Prevalence of extended-spectrum beta-lactamase-producing Escherichia coli in a
      tertiary care hospital in Tehran, Iran.
AB  - The prevalence of extended-spectrum beta-lactamase (ESBL) production by
      consecutive, non-repeated Escherichia coli isolates from hospitalised patients
      was determined over the period from July 2005 to November 2006. A total of 201 E.
      coli were isolated from various clinical specimens, 135 (67.2%) of which were
      confirmed as ESBL-positive using the combination disk synergy test. By univariate
      analysis, male sex, intravascular or urinary catheterisation, recent surgery or
      hospitalisation and isolation of E. coli from wound or respiratory tube specimens
      were found to be risk factors for acquisition of resistant bacteria (chi(2) test,
      P<0.05). However, binary logistic multivariate regression analysis confirmed that
      isolation of E. coli from urine samples of either males in any hospital ward (odd
      ratio (OR) 7.52, 95% confidence interval (CI) 1.21-47.62; P=0.031) or patients
      with prior surgery (OR 13.16, 95% CI 1.81-100.00; P=0.011) were significantly
      associated with ESBL production. Imipenem, amikacin and piperacillin/tazobactam
      were found to be highly active against ESBL-positive isolates in vitro (100%,
      91.1% and 85.2% susceptibility, respectively). They showed co-resistance with
      other antibiotics such as fluoroquinolones, gentamicin and
      trimethoprim/sulfamethoxazole. Of the 135 ESBL-positive isolates, 22 (16.3%)
      appeared to be of the CTX-M type based on a phenotypic determination method.

PMID- 18060744
TI  - Interleukin-1beta and macrophage migration inhibitory factor (MIF) in dermal
      fibroblasts mediate UVA-induced matrix metalloproteinase-1 expression.
AB  - BACKGROUND: Exposure to solar UV radiation is the main environmental factor that
      causes premature aging of the skin. Matrix metalloproteinases (MMP)-1 is a member
      of the MMP family and degrades types I and III collagens, which are the major
      structural components of the dermis. OBJECTIVE: We evaluated the involvement IL
      1beta and macrophage migration inhibitory factor (MIF) in MMP-1 expression under
      ultraviolet A (UVA) irradiation. METHODS: IL-1beta and MIF in MMP-1 expression in
      cultured human dermal fibroblasts and the UVA effects on MMPs production using IL
      1alpha/beta-deficient mice were analyzed. Furthermore, fibroblasts derived from
      MIF-deficient mice were used to analyze the effect of IL-1beta-induced MMPs
      production. RESULTS: IL-1beta-enhanced MIF expression and induced MMP-1 in
      cultured human dermal fibroblasts. IL-1beta-induced MMP-1 expression is inhibited
      by neutralizing anti-MIF antibody. Dermal fibroblasts of IL-1alpha/beta-deficient
      mice produced significantly decreased levels of MMPs compared to wild-type mice
      after UVA irradiation. Furthermore, fibroblasts of MIF-deficient mice were much
      less sensitive to IL-1beta-induced MMPs production. On the contrary, IL-1beta
      produced significantly decreased levels of MMPs in MIF-deficient mice
      fibroblasts. The up-regulation of MMP-1 mRNA by IL-1beta stimulation was found to
      be inhibited by a p38 inhibitor and a JNK inhibitor. In contrast, the MEK
      inhibitor and inhibitor were found to have little effect on expression of MMP-1
      mRNA. CONCLUSIONS: IL-1beta is involved in the up-regulation of UVA-induced MMP-1
      in dermal fibroblasts, and IL-1beta and MIF cytokine network induce MMP-1 and
      contribute to the loss of interstitial collagen in skin photoaging.

PMID- 18060746
TI  - Ciprofloxacin and furagin in acute cystitis: comparison of early immune and
      microbiological results.
AB  - Furagin (a nitrofurantoin analogue) has the same efficacy in treating acute
      cystitis as ciprofloxacin, however the duration of therapy is longer. We
      established a hypothesis that therapy with ciprofloxacin results in faster
      resolution of mucosal inflammation in comparison with furagin. Rates of urinary
      secretion of immunoglobulins class A, M and G and interleukin-8 (IL-8) were
      evaluated before and after initiation of therapy in adult women presenting with
      acute cystitis confirmed by urine culture. Women were randomised into two groups
      receiving either ciprofloxacin 250mg twice a day for 3 days (n=13) or furagin
      100mg three times a day for 7 days (n=14). Median lengths of follow-up were 4
      days and 5 days in the ciprofloxacin and furagin groups, respectively. Treatment
      with ciprofloxacin resulted in faster eradication of pathogens. No bacteria or
      nitrates were detected in the ciprofloxacin group, whilst leukocyte esterase was
      positive in only one case. In the furagin group there were four positive
      cultures, seven cases with positive nitrates and five cases with positive
      esterase. Secretion rates of all four substances dropped significantly, but the
      changes over time were similar in both groups.

PMID- 18060747
TI  - Interaction between a cationic polymethacrylate (Eudragit E100) and anionic
      drugs.
AB  - The interaction between a cationic polymethacrylate (Eudragit E, EU) and a set of
      7 drugs having acid groups (AH) was studied. Two series of complexes were
      prepared (EU-AH50 and EU-AH50Cl50), in both 50% of the basic groups of EU were
      neutralized with AH but in the second, the remaining groups were further
      neutralized with HCl. These products were stable solid ionic complexes that were
      characterized through infrared spectroscopy and X-ray power diffraction. All EU
      AH50Cl50 at 5-10mg/ml produced clear optically isotropic aqueous dispersions.
      This result was in line with the increase of the apparent solubility of the low
      solubility AH assayed. The species distribution, as determined on the complex of
      diclofenac, showed a degree of counterion condensation as high as 97.9%. The
      reversibility of the counterion condensation, as well as the affinity between EU
      and AH, was evaluated through the proton withdrawing effect produced by the ionic
      exchange generated by titration with NaCl. Besides, drug delivery in
      bicompartimental Franz cells towards water as receptor medium was very slow.
      However, it was increased as water was replaced by NaCl solution that upon
      diffusion generates ionic exchange. Therefore, the EU-AH system behaves as a
      reservoir of drug able to deliver it in simulated biological fluid.

PMID- 18060748
TI  - Modulation of methylglyoxal and glutathione by soybean isoflavones in mild
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND AND AIMS: Evidence shows that methylglyoxal (MG), a very reactive
      metabolite of glucose, plays a critical role in the pathogenesis of diabetes and
      diabetic complications. Although soy isoflavones have beneficial effects in
      diabetes, the role of soy isoflavones in regulating MG levels is unknown. The
      present study investigates the effects of soy protein isoflavones on MG and
      reduced glutathione (GSH). METHODS AND RESULTS: Mild diabetes was induced in male
      Sprague-Dawley rats by intraperitoneal injection of 35 mg/kg streptozotocin
      (STZ). The diabetic rats were then randomly divided into three groups and
      received a special diet supplemented with casein (control), low-isoflavone soy
      protein (LIS), or high-isoflavone soy protein (HIS) for eight weeks,
      respectively. Compared to the control or LIS group, HIS diet significantly
      increased serum insulin levels (p<0.01 or 0.05) and reduced serum glucose and MG
      levels (p<0.05). Serum GSH levels were increased in HIS-fed rats compared with
      the control or LIS group (p<0.01). Serum total cholesterol and homocysteine
      levels were significantly lower in HIS and LIS rats than those of the control
      rats. CONCLUSIONS: Both LIS and HIS diets can lower serum lipid and homocysteine
      levels in this mild diabetic model. HIS diet enhances insulin secretion and
      reduces glucose level. Moreover, the HIS diet has potential in reducing MG and
      increasing GSH levels. In addition to its hypoglycemic effect, the antioxidant
      protection may provide beneficial effects in preventing the development of
      diabetic complications.

PMID- 18060749
TI  - Importance of glycemic control on the course of glomerular filtration rate in
      type 2 diabetes with hypertension and microalbuminuria under tight blood pressure
      control.
AB  - BACKGROUND AND AIMS: To evaluate the role of glycemic control on the evolution of
      glomerular filtration rate (GFR) in type 2 diabetes (T2DM) with mild-moderate
      hypertension under tight blood pressure control, and to address the current
      controversy whether diabetic nephropathy worsens, independently of blood
      pressure, proportionally to HbA1c at any physiological level or only when HbA1c
      is above a 7.5-8% threshold. METHODS AND RESULTS: T2DM (N=127) during early stage
      diabetic nephropathy characterized by microalbuminuria were followed during a 2
      year multicenter study. Individual GFR profiles were accurately obtained by
      (51)Cr - EDTA bolus injections and analyzed with linear statistical mixed-effects
      models. GFR at baseline was significantly negatively correlated with age and
      plasma creatinine concentration (P<or=0.0001), and GFR declined, on average, by
      4.0 ml/min 1.73 m(2)/year (P=0.001). A significant correlation was found between
      individual GFR decline rate and average systolic (SBP) and diastolic (DBP) blood
      pressures (-0.254 (0.736) ml/min 1.73 m(2)/year per mmHg increase in SBP (DBP),
      P=0.041 (0.014)) and % of glycated hemoglobin (HbA1c) (-1.78 ml/min 1.73
      m(2)/year per % increase in HbA1c, P=0.048). This implies a 44%
      increase/reduction in GFR decline rate for 1% HbA1c increase/reduction around
      7.0% (i.e. 5.79 and 2.24 ml/min 1.73 m(2)/year at 8% and 6% HbA1c, respectively).
      CONCLUSIONS: This study demonstrates that, despite tight blood pressure control,
      an accurate glycemic control till very low patterns of HbA1c (from 10-11% to 5
      6%) is needed to delay the progression of GFR decay in Mediterranean T2DM in
      south Europe with microalbuminuria.

PMID- 18060750
TI  - Effects of oleic acid and macrophage recruitment on cholesterol efflux in cell
      culture and in vivo.
AB  - BACKGROUND AND AIM: Monounsaturated fatty acids in diets are beneficial for the
      plasma lipoprotein profile, but studies in cell culture point out that they may
      also be detrimental by inhibiting cholesterol efflux to apo AI. METHODS AND
      RESULTS: In the present study we used mouse peritoneal macrophages, loaded with
      cholesterol and upregulated by cyclic AMP or by LXR/RXR ligands and compared the
      effect of oleic acid on cholesterol efflux to 3 different acceptors. Inhibition
      of cholesterol efflux by oleic acid ranged from 10 to 25% with HDL or 2.5% mouse
      serum, while efflux to phosphatidyl choline vesicles was not affected. Previously
      we reported that the LXR ligand, TO901317, retarded cholesterol removal in vivo
      from a modified LDL depot in muscle. This could have resulted from inhibition by
      unsaturated fatty acids or from reduction in macrophage recruitment due to the
      anti-inflammatory action of LXR. CONCLUSIONS: Our current findings, of
      retardation of cholesterol clearance from the depot in the presence of low
      macrophage recruitment, support the latter possibility.

PMID- 18060751
TI  - Hyperinsulinemia and insulin resistance are independently associated with plasma
      lipids, uric acid and blood pressure in non-diabetic subjects. The GISIR
      database.
AB  - BACKGROUND AND AIMS: We evaluated whether hyperinsulinemia and/or insulin
      resistance are independently associated with plasma lipids, uric acid and blood
      pressure in non-diabetic subjects. METHODS AND RESULTS: A database of non
      diabetic Italian subjects has recently been set up using data from
      hyperinsulinemic euglycemic clamp studies carried out using the standard
      technique (40 mU per min per square meter of body surface area). In this database
      we evaluated the relationships between fasting plasma insulin (FPI), glucose
      metabolized during clamp (M) and plasma levels of triglycerides (TG), high
      density lipoprotein cholesterol (HDL-C), uric acid (UA) as well as blood pressure
      (BP) in non-diabetic subjects with fasting plasma glucose <6.1 mmol/l. Parallel
      analyses were conducted in all subjects in the database (n=1093) and in those
      with all variables available (n=309). In the univariate analysis both FPI and M
      were significantly correlated with TG, HDL-C, UA and BP (systolic, diastolic and
      mean). Multivariate regression analyses including center, sex, age, body mass
      index (BMI), FPI and M as independent variables showed that: (1) TG and UA were
      positively correlated with FPI and negatively correlated with M; (2) HDL-C was
      negatively correlated with FPI and positively correlated with M; and (3) BP was
      negatively correlated with both FPI and M. Analyses of covariance showed that,
      after adjusting for center, sex, age and BMI, subjects with isolated
      hyperinsulinemia or isolated insulin resistance had higher TG and UA and lower
      HDL-C. Subjects with isolated insulin resistance had also higher BP whereas
      subjects with isolated hyperinsulinemia had lower BP. Subjects with both defects
      had a worse profile. CONCLUSIONS: Hyperinsulinemia and insulin resistance might
      contribute with distinct and independent mechanisms to the development of several
      metabolic and hemodynamic disorders often clustering in the same individual. In
      particular, hypertriglyceridemia, low HDL-cholesterol and hyperuricemia seem to
      be related to both hyperinsulinemia and insulin resistance, whereas hypertension
      seems to be related only to insulin resistance.

PMID- 18060752
TI  - Fatty acids in cord blood plasma, the relation to soluble CD23 and subsequent
      atopy.
AB  - Atopy is suggested to be linked to the balance between levels of n-6 and n-3
      series of long chain polyunsaturated fatty acids (PUFAs) in the diet. In a nested
      case-control study, levels of fatty acids, IgE and soluble low affinity IgE
      receptor (sCD23) were measured in cord blood in 35 children who subsequently
      developed allergic sensitisation and atopic dermatitis before the age of 3, and
      similarly in 35 matched children without a history of atopy. We found a tendency
      to lower levels of the n-3 PUFAs eicosapentaenoic acid (EPA) and alpha-linolenic
      acid (ALA) in the cord blood plasma of atopics compared to non-atopics. Levels of
      sCD23 were negatively correlated to levels of n-3 series of PUFAs and n-9
      eicosenoic acid, and levels of n-9 eicosenoic acid was negatively correlated to
      levels of IgE. There was no association between the levels of sCD23 and n-6
      PUFAs. Lower levels of n-3 PUFAs in cord blood may be associated with the
      development of atopy in children. A possible mechanism may be through the
      regulation of CD23, thereby influencing IgE synthesis.

PMID- 18060753
TI  - n-3 Fatty acids and cardiovascular disease: actions and molecular mechanisms.
AB  - Cardiovascular disease and atherosclerosis are a leading cause of morbidity and
      mortality worldwide. Epidemiological studies and randomized control intervention
      trials have reported that n-3 fatty acids reduce cardiovascular events. A variety
      of biologic and molecular effects of n-3 fatty acids can modulate the mechanisms
      of development and progression of atherosclerosis. These include n-3 fatty acid
      effects on inflammation, cardiac excitability, platelet function, triglyceride
      blood levels, blood pressure and the stability of atheroma plaques. The molecular
      mechanisms are still not fully defined; but might involve changes in membrane
      fluidity, receptor responses and binding to intracellular receptors regulating
      gene transcription. Understanding and elucidating these mechanisms is important
      to development of future strategies for prevention and treatment of
      cardiovascular disease.

PMID- 18060755
TI  - Docosanoids are multifunctional regulators of neural cell integrity and fate:
      significance in aging and disease.
AB  - The identification of neuroprotectin D1 (NPD1), a biosynthetic product of
      docosahexaenoic acid (DHA), in brain and retina as well as the characterization
      of its bioactivity, is generating a renewed interest in the functional role and
      pathophysiological significance of omega-3 fatty acids in the central nervous
      system. Neurotrophins, particularly pigment epithelium-derived factor (PEDF),
      induce NPD1 synthesis and its polarized apical secretion, implying paracrine and
      autocrine bioactivity of this lipid mediator. Also, DHA and PEDF synergistically
      activate NPD1 synthesis and antiapoptotic protein expression and decreased
      proapoptotic Bcl-2 protein expression and caspase 3 activation during oxidative
      stress. In experimental stroke, endogenous NPD1 synthesis was found to be
      upregulated, and the infusion of the lipid mediator into the brain under these
      conditions revealed neuroprotective bioactivity of NPD1. The hippocampal CA1
      region from Alzheimer's disease (AD) patients (rapidly sampled) shows a major
      reduction in NPD1. The interplay of DHA-derived neuroprotective signaling aims to
      counteract proinflammatory, cell-damaging events triggered by multiple,
      converging cytokine and amyloid peptide factors, as in the case of AD. Generation
      of NPD1 from DHA thereby appears to redirect cellular fate toward successful
      preservation of retinal pigment epithelial (RPE)-photoreceptor cell integrity and
      brain cell aging. The Bcl-2 pro- and antiapoptotic proteins, neurotrophins, and
      NPD1, lie along a cell fate-regulatory pathway whose component members are highly
      interactive, and have potential to function cooperatively in cell survival.
      Agents that stimulate NPD1 biosynthesis, NPD1 analogs, or dietary regimens may be
      useful as new preventive/therapeutic strategies for neurodegenerative diseases.

PMID- 18060756
TI  - Nucleic acid recognizing Toll-like receptors and autoimmunity.
AB  - The understanding of autoimmune diseases experienced an impressive boost since
      the Toll-like receptors (TLRs) have been identified as possible key players in
      autoimmune pathophysiology. Although these receptors recognize a variety of
      structures derived from viruses, bacteria, and fungi leading to subsequent
      initiation of the relevant immune responses, recent data support the idea that
      TLRs are crucial in the induction and perpetuation of certain autoimmune
      diseases, especially the systemic lupus erythematosus (SLE). In this review, we
      will summarize recent data on involvement of TLRs in the development of
      autoimmune diseases. We will focus on TLRs 7, 8, and 9 that were originally
      identified as receptors specific for bacterial and viral RNA/DNA, but more recent
      in vitro and in vivo studies have linked these receptors to the detection of host
      RNA, DNA, and RNA-associated or DNA-associated proteins in the context of
      autoimmunity.

PMID- 18060754
TI  - Brain metabolism of nutritionally essential polyunsaturated fatty acids depends
      on both the diet and the liver.
AB  - Plasma alpha-linolenic acid (alpha-LNA, 18:3n-3) and linoleic acid (LA, 18:2n-6)
      do not contribute significantly to the brain content of docosahexaenoic acid
      (DHA, 22:6n-3) or arachidonic acid (AA, 20:4n-6), respectively, and neither DHA
      nor AA can be synthesized de novo in vertebrate tissue. Therefore, measured rates
      of incorporation of circulating DHA and AA into brain exactly represent their
      rates of consumption by brain. Positron emission tomography (PET) has been used
      to show, based on this information, that the adult human brain consumes AA and
      DHA at rates of 17.8 and 4.6 mg/day, respectively, and that AA consumption does
      not change significantly with age. In unanesthetized adult rats fed an n-3 PUFA
      "adequate" diet containing 4.6% alpha-LNA (of total fatty acids) as its only n-3
      PUFA, the rate of liver synthesis of DHA was more than sufficient to maintain
      brain DHA, whereas the brain's rate of DHA synthesis is very low and unable to do
      so. Reducing dietary alpha-LNA in the DHA-free diet led to upregulation of liver
      but not brain coefficients of alpha-LNA conversion to DHA and of liver expression
      of elongases and desaturases that catalyze this conversion. Concurrently, brain
      DHA loss slowed due to downregulation of several of its DHA-metabolizing enzymes.
      Dietary alpha-LNA deficiency also promoted accumulation of brain docosapentaenoic
      acid (22:5n-6), and upregulated expression of AA-metabolizing enzymes, including
      cytosolic and secretory phospholipases A(2) and cyclooxygenase-2. These changes,
      plus reduced levels of brain derived neurotrophic factor (BDNF) and cAMP response
      element-binding protein (CREB) in n-3 PUFA diet deficient rats, likely render
      their brain more vulnerable to neuropathological insults.

PMID- 18060757
TI  - Parenchymal pseudotumoral tuberculosis: case series and systematic review of
      literature.
AB  - Tuberculosis is a rampant infectious pandemic worldwide, with an annual incidence
      of 8 million active cases and 2 million deaths. Tuberculosis is also among the
      leading causes of solitary pulmonary nodule in the tropics. Although lymph nodal
      masses are common in tuberculosis, parenchymal masses are distinctly rare. We
      report eight immunocompetent adults admitted with large pulmonary masses, and
      ultimately diagnosed to have parenchymal pseudotumoral tuberculosis. Clinical and
      radiological resolution followed anti-tubercular therapy alone. We have also
      conducted a MEDLINE search and summarize the clinical features of all patients
      with parenchymal pseudotumoral tuberculosis. We also compare our findings with
      published literature and discuss the possible mechanisms leading to large
      inflammatory masses, clinical and radiologic clues to the same, common errors in
      clinical decision making and the therapy of this rare entity.

PMID- 18060758
TI  - Aerosolized colistin as adjunctive treatment of ventilator-associated pneumonia
      due to multidrug-resistant Gram-negative bacteria: a prospective study.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) remains the leading cause of
      death in patients with intensive care unit (ICU) acquired infections associated
      with an attributable mortality around 30%. Increasing antimicrobial resistance in
      patients with VAP challenges intensivists to search for alternative therapeutic
      options. There is scarcity of data in the literature concerning the
      administration of aerosolized colistin in critically ill patients with VAP due to
      multidrug-resistant (MDR) Gram-negative pathogens. METHODS: To assess the safety
      and effectiveness of aerosolized colistin as an adjunctive to the intravenous
      antimicrobial therapy for the treatment of VAP due to MDR Gram-negative
      pathogens, we prospectively examined all patients, who received inhaled colistin.
      RESULTS: Sixty critically ill patients with a mean APACHE II score 16.7, received
      aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter
      baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella
      pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were
      susceptible only to colistin. Mean (+/-SD) daily dosage of aerosolized colistin
      was 2.2 (+/-0.7) million international units (IU). All patients received 2946
      inhalations of colistin and the mean duration of administration was 16.4 days.
      Fifty-seven patients received concomitant intravenous treatment with colistin or
      other antimicrobial agents. Bacteriological and clinical response of VAP was
      observed in 50/60 (83.3%) patients. No adverse effects related to inhaled
      colistin were recorded. All cause hospital mortality was 25% while mortality
      attributable to VAP was 16.7%. CONCLUSIONS: Aerosolized colistin may be
      considered as adjunctive to intravenous treatment in patients with VAP due to MDR
      Gram-negative bacteria susceptible to colistin in critically ill patients.
      Although colistin is safe and effective, the best route of administration remains
      unclear. In addition, controlled comparative studies are needed to establish its
      effectiveness and safety.

PMID- 18060759
TI  - GIS-based approach for optimized siting of municipal solid waste landfill.
AB  - The exponential rise in the urban population of the developing countries in the
      past few decades and the resulting accelerated urbanization phenomenon has
      brought to the fore the necessity to develop environmentally sustainable and
      efficient waste management systems. Sanitary landfill constitutes one of the
      primary methods of municipal solid waste disposal. Optimized siting decisions
      have gained considerable importance in order to ensure minimum damage to the
      various environmental sub-components as well as reduce the stigma associated with
      the residents living in its vicinity, thereby enhancing the overall
      sustainability associated with the life cycle of a landfill. This paper addresses
      the siting of a new landfill using a multi-criteria decision analysis (MCDA) and
      overlay analysis using a geographic information system (GIS). The proposed system
      can accommodate new information on the landfill site selection by updating its
      knowledge base. Several factors are considered in the siting process including
      geology, water supply resources, land use, sensitive sites, air quality and
      groundwater quality. Weightings were assigned to each criterion depending upon
      their relative importance and ratings in accordance with the relative magnitude
      of impact. The results from testing the system using different sites show the
      effectiveness of the system in the selection process.

PMID- 18060760
TI  - Hospital solid waste management practices in Limpopo Province, South Africa: a
      case study of two hospitals.
AB  - The shortcomings in the management practices of hospital solid waste in Limpopo
      Province of South Africa were studied by looking at two hospitals as case
      studies. Apart from field surveys, the generated hospital waste was weighed to
      compute the generation rates and was followed through various management
      practices to the final disposal. The findings revealed a major policy
      implementation gap between the national government and the hospitals. While
      modern practices such as landfill and incineration are used, their daily
      operations were not carried according to minimum standards. Incinerator ash is
      openly dumped and wastes are burned on landfills instead of being covered with
      soil. The incinerators used are also not environmentally friendly as they use old
      technology. The findings further revealed that there is no proper separation of
      wastes according to their classification as demanded by the national government.
      The mean percentage composition of the waste was found in the following
      decreasing order: general waste (60.74%)>medical waste (30.32%)>sharps (8.94%).
      The mean generation rates were found to be 0.60kg per patient per day.

PMID- 18060761
TI  - Greenhouse gas emission reduction and environmental quality improvement from
      implementation of aerobic waste treatment systems in swine farms.
AB  - Trading of greenhouse gas (GHG) emission reductions is an attractive approach to
      help producers implement cleaner treatment technologies to replace current
      anaerobic lagoons. Our objectives were to estimate greenhouse gas (GHG) emission
      reductions from implementation of aerobic technology in USA swine farms. Emission
      reductions were calculated using the approved United Nations framework convention
      on climate change (UNFCCC) methodology in conjunction with monitoring information
      collected during full-scale demonstration of the new treatment system in a 4360
      head swine operation in North Carolina (USA). Emission sources for the project
      and baseline manure management system were methane (CH4) emissions from the
      decomposition of manure under anaerobic conditions and nitrous oxide (N2O)
      emissions during storage and handling of manure in the manure management system.
      Emission reductions resulted from the difference between total project and
      baseline emissions. The project activity included an on-farm wastewater treatment
      system consisting of liquid-solid separation, treatment of the separated liquid
      using aerobic biological N removal, chemical disinfection and soluble P removal
      using lime. The project activity was completed with a centralized facility that
      used aerobic composting to process the separated solids. Replacement of the
      lagoon technology with the cleaner aerobic technology reduced GHG emissions
      96.9%, from 4972 tonnes of carbon dioxide equivalents (CO2-eq) to 153 tonnes CO2
      eq/year. Total net emission reductions by the project activity in the 4360-head
      finishing operation were 4776.6 tonnes CO2-eq per year or 1.10 tonnes CO2-eq/head
      per year. The dollar value from implementation of this project in this swine farm
      was US$19,106/year using current Chicago Climate Exchange trading values of
      US$4/t CO2. This translates into a direct economic benefit to the producer of
      US$1.75 per finished pig. Thus, GHG emission reductions and credits can help
      compensate for the higher installation cost of cleaner aerobic technologies and
      facilitate producer adoption of environmentally superior technologies to replace
      current anaerobic lagoons in the USA.

PMID- 18060762
TI  - Performance evaluation of cement stabilized fly ash-GBFS mixes as a highway
      construction material.
AB  - Fly ash and granulated blast furnace slag (GBFS) are major by-products of thermal
      and steel plants, respectively. These materials often cause disposal problems and
      environmental pollution. Detailed laboratory investigations were carried out on
      cement stabilized fly ash-(GBFS) mixes in order to find out its suitability for
      road embankments, and for base and sub-base courses of highway pavements. Proctor
      compaction test, unconfined compressive strength (UCS) test and California
      Bearing Ratio (CBR) test were conducted on cement stabilized fly ash-GBFS mixes
      as per the Indian Standard Code of Practice. Cement content in the mix was varied
      from 0% to 8% at 2% intervals, whereas the slag content was varied as 0%, 10%,
      20%, 30% and 40%. Test results show that an increase of either cement or GBFS
      content in the mixture, results in increase of maximum dry density (MDD) and
      decrease of optimum moisture content (OMC) of the compacted mixture. The MDD of
      the cement stabilized fly ash-GBFS mixture is comparably lower than that of
      similarly graded natural inorganic soil of sand to silt size. This is
      advantageous in constructing lightweight embankments over soft, compressible
      soils. An increase in percentage of cement in the fly ash-GBFS mix increases
      enormously the CBR value. Also an increase of the amount of GBFS in the fly ash
      sample with fixed cement content improves the CBR value of the stabilized mix. In
      the present study, the maximum CBR value of compacted fly ash-GBFS-cement
      (52:40:8) mixture obtained was 105%, indicating its suitability for use in base
      and sub-base courses in highway pavements with proper combinations of raw
      materials.

PMID- 18060763
TI  - Towards the real-time monitoring of glucose in tear fluid: holographic glucose
      sensors with reduced interference from lactate and pH.
AB  - Glucose-selective holographic sensors were fabricated from unique tetrahedral 2
      acrylamidophenylboronic acid (2-APB) incorporated with co-monomers poly(ethylene
      glycol) acrylate (PEG), (3-acrylamidopropyl)trimethylammonium chloride (ATMA) and
      [2-(acryloyloxy)ethyl]-trimethylammonium chloride (AETA) into thin hydrogel films
      which were transformed into volume holograms using a diffusion method coupled
      with holographic recording using a frequency-doubled Nd:YAG laser (532 nm). The
      results showed that the 2-APB-based holographic sensors contracted upon addition
      of glucose due to the formation of a 2:1 complex between the tetrahedral 2-APB
      and glucose. More significantly, the 2-APB-based holographic sensors had greatly
      reduced lactate dependence and a hugely reduced pH effect over the physiological
      range of pH. These features are vital for development of contact lens-based
      glucose sensor, where the pH variability is greater (pH 5.8-7.8) and the lactate
      concentration is substantially higher than in blood. Furthermore, the 2-APB-based
      holographic sensors also displayed fast response to glucose. The successful union
      of holograms and the tetrahedral 2-APB receptor for glucose detection in
      artificial tear fluid is also demonstrated. This new type of holographic sensors
      responding to glucose with features of minor pH effect and negligible
      interference from lactate is applicable to the detection of glucose
      concentrations in tear fluid for the management of diabetes.

PMID- 18060764
TI  - Genomics to tree breeding and forest health.
AB  - Genomic discovery in forest trees follows paradigms from both agricultural crop
      and livestock improvement and human medicine. Forest trees in a domesticated
      state can be improved using genomic-based breeding technologies, whereas the
      health of trees in a natural and undomesticated state might be managed using
      those same technologies. These applications begin by first dissecting complex
      traits in trees to their individual gene components and for that the association
      genetics approach is quite powerful in trees. This is true for several reasons
      including large, random mating, and unstructured populations and the rapid decay
      of linkage disequilibrium in many tree species. Once marker by trait associations
      are discovered, they can be used in genomic-based breeding and forest health
      diagnostics. Initial studies in trees have found ample nucleotide diversity in
      candidate genes to perform association studies and single nucleotide
      polymorphisms have been associated with economic and adaptive traits. Population
      genetic neutrality tests have been applied to identify genes probably under
      natural selection and thus make good candidates for developing forest health
      diagnostic tools.

PMID- 18060765
TI  - How to assess anti-tumour efficacy by imaging techniques.
AB  - Response evaluation in the assessment of potential new anti-cancer therapies is
      undergoing intense investigation and change. Current imaging techniques most
      commonly used in early phase clinical trials are limited to providing reliable
      and reproducible anatomical data demonstrating a change in size and reduction in
      tumour volume thereby inferring patient benefit. Current imaging modalities such
      as computed tomography (CT) and magnetic resonance imaging (MRI) by their nature
      require computer programs and software. This is a constantly evolving field and
      upgraded technology enables faster acquisition times for scans, greater
      anatomical detail and accurate volumetric data to be acquired. Dynamic studies
      allow contrast agents to be visualised in any given structure over time, so blood
      flow, blood volume and permeability can be assessed thereby demonstrating
      function. The advent of many new anti-cancer agents with novel modes of action
      such as anti-angiogenesis agents act by preventing the development of a suitable
      blood supply to sustain tumour growth. Such agents do not actively destroy tumour
      cells so do not exhibit a 'cytocidal' effect as traditional anti-cancer agents do
      but prevent tumour growth, so can be regarded as 'cytostatic' agents. Therefore,
      traditional response evaluation criteria may not be appropriate to assess drug
      efficacy or 'activity' in achieving patient benefit. New techniques have also
      been developed so the 'function' or metabolism can be demonstrated and tumour
      serum markers and other factors also require consideration rather than relying on
      a single modality alone. This article reviews the current accepted response
      criteria and highlights some newer techniques which will almost certainly play a
      major role in the assessment of new anti-cancer therapy, particularly in the
      development of cytostatic agents which are playing an ever increasing role.

PMID- 18060766
TI  - Pilot study of anti-angiogenic vaccine using fixed whole endothelium in patients
      with progressive malignancy after failure of conventional therapy.
AB  - Vaccines targeting tumour angiogenesis were recently shown to inhibit tumour
      growth in animal models. However, there is still a lack of information about the
      clinical utility of anti-angiogenic vaccination. Therefore, here, we aimed to
      test the clinical effects of a vaccine using glutaraldehyde-fixed human umbilical
      vein endothelial cells (HUVECs). Six patients with recurrent malignant brain
      tumours and three patients with metastatic colorectal cancer received intradermal
      injections of 5x10(7) HUVECs/dose (in total 230 vaccinations). ELISA and flow
      cytometry revealed immunoglobulin response against HUVECs' membrane antigens.
      ELISPOT and chromium-release cytotoxicity assay revealed a specific cellular
      immune response against HUVECs, which were lysed in an effectors:targets ratio
      dependent manner. Gadolinium-contrasted MRI showed partial or complete tumour
      responses in three malignant brain tumour patients. Except for a DTH-like skin
      reaction at the injection site, no adverse effect of vaccination could be
      observed. Our results suggest that the endothelial vaccine can overcome
      peripheral tolerance of self-angiogenic antigens in clinical settings, and
      therefore should be useful for adjuvant immunotherapy of cancer.

PMID- 18060767
TI  - Red clover isoflavones biochanin A and formononetin are potent ligands of the
      human aryl hydrocarbon receptor.
AB  - Aryl hydrocarbon receptor (AhR) activation affects the cell cycle and drives
      cells to apoptosis. Thus, selective AhR modulators (SAhRMs) have previously been
      implicated in cancer therapy and prevention, particularly for hormone-dependent
      cancers. In the present study, isoflavones a remedy used to ameliorate menopausal
      complaints were tested for their potential in transactivating AhR in order to
      investigate the biological function of red clover isoflavones. The results were
      compared to the transactivation potentials of other flavonoids and plant-derived
      indole compounds. We found that the isoflavones biochanin A and formononetin were
      potent AhR agonists in vitro, with EC(50) values of 2.5 x 10(-7) and 1.3 x 10(
      7)mol/l, respectively. These isoflavones are 10 times more potent compared to the
      indole compounds indole-3-carbinol and diindolylmethane, publicised as powerful
      AhR agonists with EC(50) values of 5.8 x 10(-6) and 1.1 x 10(-6)mol/l,
      respectively. Because activated AhR crosstalks with estrogen receptor alpha,
      future risk-benefit assessments of isoflavones should take into consideration
      their AhR transactivating potential.

PMID- 18060768
TI  - Radiofrequency-assisted liver resection.
AB  - BACKGROUND: Surgical resection remains the treatment of choice for primary,
      secondary liver cancer and a number of benign liver lesions. Complications are
      mainly related to blood loss. Radiofrequency-assisted liver resection (RF-LR) has
      been proposed in order to achieve minimal blood loss during parenchymal
      transection. PATIENTS AND METHODS: Between May 2005 and April 2007, 46
      consecutive patients with various hepatic lesions underwent RF-LR using
      Radionics, Cool-Tip System. There were 28 men and 18 women with median age 65
      years (range 54-76 years). Twelve major and 34 minor hepatectomies were performed
      for various diseases: hepatocellular carcinoma (n=19), metastatic carcinoma
      (n=23), focal nodal hyperplasia (n=2) and intrahepatic cholangiocarcinoma (ICC)
      (n=2). Hepatic inflow occlusion was not used. RESULTS: No perioperative death was
      documented. Median blood loss was 100ml (range 30-300cm(3)). Blood transfusion
      was required postoperatively in one patient. Median transection time was 35min
      (15-60min). Three patients developed biliary fistulas, four patients pleural
      effusions, one patient hyperbilirubinemia, two pneumonia and four wound
      infection. The median postoperative hospital stay was 6 days (range 4-10 days).
      In a median 12 month follow-up (range 3-24 months), four patients with colorectal
      metastases (CRM) and one patient with ICC developed recurrence. CONCLUSIONS: Cool
      Tip RF device provides a unique, simple and safe method of bloodless liver
      resections and is indicated in cirrhotic patients with challenging hepatectomies
      (segment VIII, central resections).

PMID- 18060769
TI  - The effect of landfill age on municipal leachate composition.
AB  - The influence of municipal landfill age on temporal changes in municipal leachate
      quality on the basis of elaboration of 4 years monitoring of leachate from
      landfill in Wysieka near Bartoszyce (Poland) is presented in this study. In
      leachate, concentrations of organic compounds (COD, BOD(5)), nutrients (nitrogen,
      phosphorus), mineral compounds, heavy metals and BTEX were investigated. It was
      shown that the principal pollutants in leachate were organics and ammonia - as
      landfill age increased, organics concentration (COD) in leachate decreased from
      1,800 mg COD/l in the second year of landfill exploitation to 610 mg COD/l in the
      sixth year of exploitation and increase of ammonia nitrogen concentration from 98
      mg N(NH)/l to 364 mg N(NH4) /l was observed. Fluctuation of other indexes
      (phosphorus, chlorides, calcium, magnesium, sulfate, dissolved solids, heavy
      metals, BTEX) depended rather on season of the year (seasonal variations) than
      landfill age. Moreover, the obtained data indicate that despite of short
      landfill's lifetime some parameters e.g. high pH (on average 7.84), low COD
      concentration (<2,000 mg COD/l), low BOD(5)/COD ratio (<0.4) and low heavy metal
      concentration, indicated that the landfill was characterized by methanogenic
      conditions already at the beginning of the monitoring period.

PMID- 18060770
TI  - A new approach to study the decolorization of complex reactive dye bath effluent
      by biosorption technique.
AB  - This work focused on the development of a practical biosorbent for the
      decolorization of textile effluents. The fermentation waste, Corynebacterium
      glutamicum biomass, when decarboxylated and immobilized in polysulfone matrix
      performed well in decolorization of simulated reactive dye bath effluent
      comprised of four different reactive dyes and other auxiliary chemicals. The
      regeneration of polysulfone-immobilized C. glutamicum was successful with the aid
      of 0.01 M NaOH as the eluant, which enabled the biosorbent to maintain consistent
      decolorization efficiency for up to 25 cycles. An up-flow packed column loaded
      with polysulfone-immobilized biomass performed well in the continuous treatment
      of Remazol effluent. Samples collected after 14 h of column operation revealed
      almost zero color and TOC. The column was also able to decrease the TDS level
      from 55,840 to 33,480 mg/L. Column regeneration experiments revealed that the
      biosorbent was able to continuously treat Remazol effluent over ten cycles, with
      more than 90.6% decolorization efficiency.

PMID- 18060771
TI  - Feasibility of using constructed wetland treatment for molasses wastewater
      treatment.
AB  - The surface flow constructed wetland (SFCW) with Cyperus involucratus, Typha
      augustifolia and Thalia dealbata J. Fraser was applied to treat anaerobic treated
      molasses wastewater (An-MWW) under the organic loading rates (OLRs) of 612, 696,
      806, 929 and 1,213 kg BOD(5)ha(-1)day(-1). The results showed that both removal
      efficiency and plant growth rate were increased with the decrease of organic
      loading rate (OLR). All tested-plant species could not grow under OLR of higher
      than 696 kg BOD(5)mg l(-1) (p>0.05). Also, the plant-biomass of the systems was
      reduced by 10.4%, 26.5%, and 64.7% of initial plant-biomass under the OLR of 806,
      929 and 1,213 kg BOD(5)ha(-1)day(-1), respectively. However, all tested-plant
      species showed the same pattern on the plant-biomass production yield and removal
      efficiency. The highest SS, BOD, COD, total phosphorus, NH(4)(+), NO(3)(-) and
      molasses pigments (MP) removal efficiencies of 90-93%, 88-89%, 67%, 70-76%, 77
      82%, 94-95% and 72-77%, respectively were detected under the OLR of 612 kg
      BOD(5)ha(-1)day.

PMID- 18060772
TI  - Identification and synthesis of a unique thiocarbazate cathepsin L inhibitor.
AB  - Library samples containing 2,5-disubstituted oxadiazoles were identified as
      potent hits in a high throughput screen (HTS) of the NIH Molecular Libraries
      Small Molecule Repository (MLSMR) directed at discovering inhibitors of cathepsin
      L. However, when synthesized in pure form, the putative actives were found to be
      devoid of biological activity. Analyses by LC-MS of original library samples
      indicated the presence of a number of impurities, in addition to the oxadiazoles.
      Synthesis and bioassay of the probable impurities led to the identification of a
      thiocarbazate that likely originated via ring opening of the oxadiazole.
      Previously unknown, thiocarbazates (-)-11 and (-)-12 were independently
      synthesized as single enantiomers and found to inhibit cathepsin L in the low
      nanomolar range.

PMID- 18060773
TI  - Synthesis and biological activity of phosphatidylinositol-3,4,5
      trisphosphorothioate.
AB  - Metabolically-stabilized analogs of PtdIns(3,4,5)P(3) have shown long-lived
      agonist activity for cellular events mediated by this phosphoinositide. We
      describe an efficient method for the total asymmetric synthesis of the
      trisphosphorothioate (PT) analog of PtdIns(3,4,5)P(3). Intracellular delivery of
      dipalmitoyl PtdIns(3,4,5)PT(3)-mimicked insulin in activating sodium transport in
      A6 cells.

PMID- 18060774
TI  - Chemical modulators of heat shock protein 70 (Hsp70) by sequential, microwave
      accelerated reactions on solid phase.
AB  - Molecular chaperones, such as Hsp70 and Hsp90, are responsible for a variety of
      protective, anti-apoptotic functions. While inhibitors of Hsp90, such as
      geldanamycin and its derivative 17-AAG, are well known and important anti-cancer
      leads, Hsp70 has received less attention. Interesting lead candidates for Hsp70
      share a dihydropyrimidine core; however, the preferred display of pendant
      functionality is still not clear. Here, we take advantage of the versatility of
      peptides to explore the requirements for activity. An exploratory compound
      collection was assembled by performing a Biginelli cyclocondensation at the
      terminus of a resin-bound beta-peptide. Liberation from solid support yielded
      peptide-modified dihydropyrimidines and, within this series, we uncovered
      compounds that alter the ATPase activity of Hsp70 and its bacterial ortholog,
      DnaK. Moreover, we identified important contributions made by aromatic,
      hydrophobic groups. These chemical probes could be used to study the roles of
      this molecular chaperone in disease.

PMID- 18060775
TI  - Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2).
AB  - A class of biaryl benzamides was identified and optimized as selective HDAC1&2
      inhibitors (SHI-1:2). These agents exhibit selectivity over class II HDACs 4-7,
      as well as class I HDACs 3 and 8; providing examples of selective HDAC inhibitors
      for the HDAC isoforms most closely associated with cancer. The hypothesis for the
      increased selectivity is the binding of a pendant aromatic group in the internal
      cavity of the HDAC1&2 enzymes. SAR development based on an initial lead led to a
      series of potent and selective inhibitors with reduced off-target activity and
      tumor growth inhibition activity in a HCT-116 xenograft model.

PMID- 18060776
TI  - Design, synthesis and evaluation of trifluoromethane sulfonamide derivatives as
      new potent and selective peroxisome proliferator-activated receptor alpha
      agonists.
AB  - Starting from the structure of 5, a two-step strategy was applied to identify a
      new generation of trifluoromethane sulfonamides as potent PPARalpha agonists.
      Synthesis, in vitro and in vivo evaluation of the most potent compound are
      reported.

PMID- 18060777
TI  - Synthesis and biological activity of piperazine and diazepane amides that are
      histamine H3 antagonists and serotonin reuptake inhibitors.
AB  - The synthesis and biological activity of a new series of piperazine and diazepane
      amides is described. The new compounds are high affinity histamine H3 ligands and
      serotonin reuptake inhibitors.

PMID- 18060778
TI  - Severe sensorimotor neuropathy after intake of highest dosages of vitamin B6.
AB  - We illustrate a white caucasian patient with a severe sensorimotor neuropathy due
      to vitamin B6 hypervitaminosis. The patient used the pendulum to calculate his
      daily metabolic demands and ingested 9.6g pyridoxine/day. To our knowledge, this
      is the highest dosage of vitamin B6 administered to humans over prolonged periods
      of time ever reported in the medical literature. The unique aspect of this case
      is the muscle weakness and motor findings on electrophysiological testing in what
      is suggested by the literature to be a pure sensory neuronopathy.

PMID- 18060779
TI  - Heart transplantation in a child with LGMD2I presenting as isolated dilated
      cardiomyopathy.
AB  - Limb-girdle muscle dystrophy type 2I is associated with mutations in the gene
      encoding Fukutin-related protein. Clinical phenotypes are heterogeneous, ranging
      from isolated hyperCkemia to severe congenital muscular dystrophy. Affected
      patients frequently develop dilated cardiomyopathy, depending on evolution of
      their skeletal myopathy. We report on an 8 years-old boy presenting a severe
      dilated cardiomyopathy requiring heart transplantation. The child harbored a
      homozygous p.Leu276Ile mutation in Fukutin-related protein gene (FKRP). At the
      current age of 20 years, the patient shows persistent hyperCKemia but no clinical
      muscle weakness, CT scan showing very mild features of muscle involvement. Our
      findings add to the array of clinical presentations of FKRP mutations.

PMID- 18060780
TI  - Apolipoprotein epsilon alleles in sporadic inclusion body myositis: a
      reappraisal.
AB  - Previous studies have differed as to whether APOE epsilon4 is a susceptibility
      factor for developing sporadic inclusion body myositis (sIBM), with a positive
      association being found only in an Australian cohort of cases. We have now re
      examined this in a larger cohort of 57 sIBM cases and have also carried out a
      meta-analysis of all the published studies looking for evidence of a risk
      association or effect of APOE alleles on disease expression. Our findings argue
      against a specific role for any APOE alleles in conferring susceptibility to sIBM
      but have demonstrated a non-significant trend towards an earlier age-of-onset in
      patients with the epsilon2 allele.

PMID- 18060781
TI  - Prognostic factors in node negative premenopausal women treated with breast
      conserving therapy without adjuvant systemic therapy.
AB  - PURPOSE: To study the prognostic factors in node negative premenopausal women
      treated with breast conserving therapy (BCT) without any adjuvant systemic
      therapy. METHODS: Of the 1022 women treated with BCT at Tata Memorial Hospital,
      there was a cohort of 175 women who were premenopausal, node negative and had not
      received any adjuvant systemic therapy. BCT consisted of wide excision, complete
      axillary clearance, whole breast radiotherapy (45 Gy in 25 fractions) with 6 MV
      photons plus tumour bed boost either with brachytherapy or electrons. RESULTS:
      The median age at presentation was 38 years (range 22-51 years) and the median
      pathological tumour size was 3 cm (1-5 cm). The 5-year actuarial local control
      rate was 89.5% and the overall survival (OS) was 88%. On univariate analysis,
      lymphovascular invasion (LVI) was the only prognostic factor affecting all
      failures and disease-free survival. The 5-year local control rate in absence of
      LVI was 93.5% in contrast to 76.5% (p=0.0098) when LVI was present. Similarly,
      the OS in absence of LVI was 91% in contrast to 74% in presence of LVI (p=0.02).
      On multivariate analysis, LVI was the independent prognostic factor affecting the
      disease-free survival (p=0.001; 95% CI: 1.46-4.96). CONCLUSION: LVI emerged as
      the most important prognostic factor for node negative premenopausal women not
      receiving adjuvant systemic therapy. There is a need to take into consideration
      the presence of LVI while deciding adjuvant systemic therapy in T1N0 patients.

PMID- 18060782
TI  - Nociceptive neurons protect Drosophila larvae from parasitoid wasps.
AB  - BACKGROUND: Natural selection has resulted in a complex and fascinating
      repertoire of innate behaviors that are produced by insects. One puzzling example
      occurs in fruit fly larvae that have been subjected to a noxious mechanical or
      thermal sensory input. In response, the larvae "roll" with a motor pattern that
      is completely distinct from the style of locomotion that is used for foraging.
      RESULTS: We have precisely mapped the sensory neurons that are used by the
      Drosophila larvae to detect nociceptive stimuli. By using complementary
      optogenetic activation and targeted silencing of sensory neurons, we have
      demonstrated that a single class of neuron (class IV multidendritic neuron) is
      sufficient and necessary for triggering the unusual rolling behavior. In
      addition, we find that larvae have an innately encoded preference in the
      directionality of rolling. Surprisingly, the initial direction of rolling
      locomotion is toward the side of the body that has been stimulated. We propose
      that directional rolling might provide a selective advantage in escape from
      parasitoid wasps that are ubiquitously present in the natural environment of
      Drosophila. Consistent with this hypothesis, we have documented that larvae can
      escape the attack of Leptopilina boulardi parasitoid wasps by rolling,
      occasionally flipping the attacker onto its back. CONCLUSIONS: The class IV
      multidendritic neurons of Drosophila larvae are nociceptive. The nociception
      behavior of Drosophila melanagaster larvae includes an innately encoded
      directional preference. Nociception behavior is elicited by the ecologically
      relevant sensory stimulus of parasitoid wasp attack.

PMID- 18060783
TI  - The G2 p38-mediated stress-activated checkpoint pathway becomes attenuated in
      transformed cells.
AB  - When human cells are stressed during G2, they are delayed from entering mitosis
      via a checkpoint mediated by the p38 kinase, and this delay can be modeled by the
      selective activation of p38 with anisomycin. Here, we report, on the basis of
      live-cell studies, that 75 nM anisomycin transiently (1 hr) activates p38 which,
      in turn, rapidly and completely blocks entry into mitosis for at least 4 hr in
      all primary, telomerase- or spontaneously immortalized (p53+ and pRB+) human
      cells. However, the same treatment does not delay entry into mitosis in cancer
      cells, or the delay in entering mitosis is shortened, even though it induces a
      similar transient and comparable (or stronger) activation of p38. Because the
      primary substrate of p38, the MK2 kinase, is also transiently (1-2 hr) activated
      by anisomycin in both normal and cancer cells, checkpoint disruption in
      transformed cells occurs downstream of MK2. Finally, observations on isogenic
      lines reveal that the duration of the stress checkpoint is shortened in cells
      lacking both p53 and pRb and that the constitutive expression of an active H-Ras
      oncogene in these cells further attenuates the checkpoint via an ERK1/2-dependent
      manner. Thus, transformation leads to attenuation of the p38-mediated stress
      checkpoint. This outcome is likely selected for during transformation because it
      confers the ability to outgrow normal cells under stressful in vitro (culture) or
      in vivo (tumor) environments. Our data caution against using cancer cells to
      study how p38 produces a G2 arrest.

PMID- 18060784
TI  - Mps1 kinase promotes sister-kinetochore bi-orientation by a tension-dependent
      mechanism.
AB  - Segregation of sister chromatids to opposite spindle poles during anaphase is
      dependent on the prior capture of sister kinetochores by microtubules extending
      from opposite spindle poles (bi-orientation). If sister kinetochores attach to
      microtubules from the same pole (syntelic attachment), the kinetochore-spindle
      pole connections must be re-oriented to be converted to proper bi-orientation.
      This re-orientation is facilitated by Aurora B kinase (Ipl1 in budding yeast),
      which eliminates kinetochore-spindle pole connections that do not generate
      tension. Mps1 is another evolutionarily conserved protein kinase, required for
      spindle-assembly checkpoint and, in some organisms, for duplication of
      microtubule-organizing centers. Separately from these functions, however, Mps1
      has an important role in chromosome segregation. Here we show that, in budding
      yeast, Mps1 has a crucial role in establishing sister-kinetochore bi-orientation
      on the mitotic spindle. Failure in bi-orientation with inactive Mps1 is not due
      to a lack of kinetochore-spindle pole connections by microtubules, but due to a
      defect in properly orienting the connections. Mps1 promotes re-orientation of
      kinetochore-spindle pole connections and eliminates those that do not generate
      tension between sister kinetochores. We did not find evidence that Ipl1 regulates
      Mps1 or vice versa; therefore, they play similar, but possibly independent, roles
      in facilitating bi-orientation.

PMID- 18060785
TI  - Reversed sexual conflict in a promiscuous antelope.
AB  - A general tenet of sexual conflict theory is that males have higher optimum
      mating rates than do females and therefore should be more persistent when it
      comes to mating. However, in promiscuous species, females might benefit from high
      mating rates as a result of increased conception probability with favored males,
      whereas favored males benefit from mating selectively because of sperm depletion.
      When this results in higher optimum mating rates for females than for males,
      there is potential for reversed sexual conflicts between persistent females and
      resistant males. Here I report evidence of such a reversed sexual conflict in a
      promiscuous antelope, the African topi. Rather than mating randomly, favored
      males prefer to balance mating investment equally between females as predicted by
      strategic sperm allocation theory. Females, however, enhance their probability of
      mating with favored males through aggression toward mating pairs. Supporting the
      idea that aggressive females thereby harass males to mate at a rate that is
      suboptimal from the males' perspective, males become increasingly likely to
      counterattack aggressive females with whom they have already mated
      disproportionately, and such male counterattacks are associated with refusal to
      mate with the aggressive females. This study points to reversed sexual conflict
      as a more significant evolutionary force in promiscuous mammals than previously
      thought; however, such conflicts probably often go unnoticed because males, in
      contrast to females, can avoid mating without conspicuous resistance.

PMID- 18060786
TI  - Drosophila calcineurin promotes induction of innate immune responses.
AB  - The sophisticated adaptive immune system of vertebrates overlies an ancient set
      of innate immune-response pathways, which have been genetically dissected in
      Drosophila. Although conserved regulatory pathways have been defined,
      calcineurin, a Ca(2+)-dependent phosphatase, has not been previously implicated
      in Drosophila immunity. Calcineurin activates mammalian immune responses by
      activating the nuclear translocation of the vertebrate-specific transcription
      factors NFAT1-4. In Drosophila, infection with gram-negative bacteria promotes
      the activation of the Relish transcription factor through the Imd pathway. The
      activity of this pathway in the larva is modulated by nitric oxide (NO). Here, we
      show that the input by NO is mediated by calcineurin. Pharmacological inhibition
      of calcineurin suppressed the Relish-dependent gene expression that occurs in
      response to gram-negative bacteria or NO. One of the three calcineurin genes in
      Drosophila, CanA1, mediated NO-induced nuclear translocation of Relish in a cell
      culture assay. A CanA1 RNA interference (RNAi) transgene suppressed immune
      induction in larvae upon infection or upon treatment with NO donors, whereas a
      gain-of-function CanA1 transgene activated immune responses in untreated larvae.
      Interestingly, CanA1 RNAi in hemocytes but not the fat body was sufficient to
      block immune induction in the fat body. Thus, CanA1 provides an additional input
      into Relish-promoted immune responses and functions in hemocytes to promote a
      tissue-to-tissue signaling cascade required for robust immune response.

PMID- 18060787
TI  - Cell-cycle progression without an intact microtuble cytoskeleton.
AB  - For mammalian somatic cells, the importance of microtubule cytoskeleton integrity
      during interphase cell-cycle progression is uncertain. The loss, suppression, or
      stabilization of the microtubule cytoskeleton has been widely reported to cause a
      G1 arrest in a variable, and often high, proportion of cell populations,
      suggesting the existence of a "microtubule damage," "microtubule integrity," or
      "postmitotic" checkpoint in G1 or G2. We found that when normal human cells
      (hTERT RPE1 and primary fibroblasts) are continuously exposed to nocodazole, they
      remain in mitosis for 10-48 hr before they slip out of mitosis and arrest in G1;
      this finding is consistent with previous reports. To eliminate the persistent
      effects of prolonged mitosis, we isolated anaphase-telophase cells that were just
      finishing a mitosis of normal duration, then we rapidly and completely
      disassembled microtubules by chilling the preparations to 0 degrees C for 10
      minutes in the continuous presence of nocodazole or colcemid treatment to ensure
      that the cells entered G1 without a microtubule cytoskeleton. Without
      microtubules, cells progressed from anaphase to a subsequent mitosis with
      essentially normal kinetics. Similar results were obtained for cells in which the
      microtubule cytoskeleton was partially diminished by lower nocodazole doses or
      augmented and stabilized with taxol. Thus, after a preceding mitosis of normal
      duration, the integrity of the microtubule cytoskeleton is not subject to
      checkpoint surveillance, nor is it required for the normal human cell to progress
      through G1 and the remainder of interphase.

PMID- 18060788
TI  - Mapping of meiotic single-stranded DNA reveals double-stranded-break hotspots
      near centromeres and telomeres.
AB  - BACKGROUND: Every chromosome requires at least one crossover to be faithfully
      segregated during meiosis. At least two levels of regulation govern crossover
      distribution: where the initiating DNA double-strand breaks (DSBs) occur and
      whether those DSBs are repaired as crossovers. RESULTS: We mapped meiotic DSBs in
      budding yeast by identifying sites of DSB-associated single-stranded DNA (ssDNA)
      accumulation. These analyses revealed substantial DSB activity in
      pericentrometric regions, in which crossover formation is largely absent. Our
      data suggest that centromeric suppression of recombination occurs at the level of
      break repair rather than DSB formation. Additionally, we found an enrichment of
      DSBs within a approximately 100 kb region near the ends of all chromosomes.
      Introduction of new telomeres was sufficient for inducing large ectopic regions
      of increased DSB formation, thereby revealing a remarkable long-range effect of
      telomeres on DSB formation. The concentration of DSBs close to chromosome ends
      increases the relative DSB density on small chromosomes, providing an
      interference-independent mechanism that ensures that all chromosomes receive at
      least one crossover per homolog pair. CONCLUSIONS: Together, our results indicate
      that selective DSB repair accounts for crossover suppression near centromeres and
      suggest a simple telomere-guided mechanism that ensures sufficient DSB activity
      on all chromosomes.

PMID- 18060789
TI  - Epidural metastases from a gastrointestinal stromal tumour.
AB  - A patient with epidural metastases from a gastrointestinal stromal tumour (GIST)
      is described. We present the clinical course and the literature is reviewed.
      After standard irradiation and surgical intervention, the tyrosine kinase
      inhibitor STI571 should be considered for treatment of metastatic GIST.

PMID- 18060790
TI  - Fourth ventricle arachnoid cyst.
AB  - We report four patients with fourth ventricle arachnoid cysts. There were two
      males and two females and the ages ranged from 18 months to 52 years (average 21
      years). All patients presented with symptoms of raised intracranial pressure.
      Excision or marsupialization of the arachnoid cyst in this location was curative
      in all patients. The follow-up ranged from 1 to 14 years.

PMID- 18060791
TI  - Structural insights into hydroxycoumarin-induced apoptosis in U-937 cells.
AB  - In the present study, we sought to establish the effect of diverse structural
      related hydroxycoumarins on the proliferation, cytotoxicity, and induction of
      apoptosis in promonocytic leukemic cells (U-937). The dihydroxylated coumarins,
      7,8-dihydroxy-coumarin and esculetin, induced DNA fragmentation as well as
      characteristic morphological changes of programmed cell death in U-937 cells.
      With the aim to perform a structure-activity relationship study, the correlation
      between the physicochemical properties of the molecules and their pro-apoptotic
      activity was carried out. Results showed that the presence of two adjacent
      phenolic hydroxyl groups was the most important factor in terms of the SAR. The
      exposure of leukemic cells to 7,8-dihydroxy-coumarin evoked a phenoxyl radical
      generation that was detected by electron spin resonance spectroscopy. The present
      study suggests that reactive oxygen species generation plays a critical role in
      dihydroxycoumarin-induced apoptosis in U-937 cells. These findings further
      suggest that these compounds may have a potential therapeutic role in the
      treatment of hematological malignancies.

PMID- 18060793
TI  - An expeditious one-pot synthesis of 1,6-dideoxy-N-alkylated nojirimycin
      derivatives and their inhibitory effects on the secretion of IFN-gamma and IL-4.
AB  - An efficient 'one-pot' approach to the synthesis of 1,6-dideoxy-N-alkylated
      nojirimycin derivatives in good yields and with high stereoselectivity was
      developed. It was found that the synthetic N-alkylated iminosugars showed
      inhibitory effects on the release of the cytokines IFN-gamma and IL-4 from the
      mouse splenocytes. The preliminary structure-activity relationship was deduced
      from the activities of N-substituted iminosugars. Apart from the cytokine
      inhibitory activities, a series of glycosidase inhibitory activities were also
      examined. The present experimental data demonstrated that synthetic iminosugars
      might hold potential as immunosuppressive agents.

PMID- 18060792
TI  - Synthesis, nitric oxide release, and anti-leukemic activity of glutathione
      activated nitric oxide prodrugs: Structural analogues of PABA/NO, an anti-cancer
      lead compound.
AB  - Diazeniumdiolate anions and their prodrug forms are reliable sources of nitric
      oxide (NO) that have generated interest as promising therapeutic agents. A number
      of structural analogues of O(2)-(2,4-dinitro-5-(4-(N
      methylamino)benzoyloxy)phenyl) 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate
      (PABA/NO), an anti-cancer lead compound that is designed to release NO upon
      activation by glutathione, were prepared. The nitric oxide release patterns of
      these O(2)-(2,4-dinitrophenyl) diazeniumdiolates in the presence of glutathione
      were tested and it was found that in the absence of competing pathways, these
      compounds release nearly quantitative amounts of NO. The ability of PABA/NO and
      its structural analogues to inhibit human leukemia cell proliferation was
      determined and it was found that compounds releasing elevated amounts of NO
      displayed superior cytotoxic effects.

PMID- 18060795
TI  - Electron energy-loss spectroscopy. Preface.

PMID- 18060796
TI  - Image simulation for electron energy loss spectroscopy.
AB  - Aberration correction of the probe forming optics of the scanning transmission
      electron microscope has allowed the probe-forming aperture to be increased in
      size, resulting in probes of the order of 1 A in diameter. The next generation of
      correctors promise even smaller probes. Improved spectrometer optics also offers
      the possibility of larger electron energy loss spectrometry detectors. The
      localization of images based on core-loss electron energy loss spectroscopy is
      examined as function of both probe-forming aperture and detector size. The
      effective ionization is nonlocal in nature, and two common local approximations
      are compared to full nonlocal calculations. The affect of the channelling of the
      electron probe within the sample is also discussed.

PMID- 18060794
TI  - Design and synthesis of a siderophore conjugate as a potent PSMA inhibitor and
      potential diagnostic agent for prostate cancer.
AB  - A siderophore conjugate was designed as a potential PSMA inhibitor and diagnostic
      agent for prostate cancer. A semi-rigid spacer was incorporated to avoid
      competitive participation of iron binding by the enzyme inhibitor relative to the
      siderophore component. Biological test results showed that, even with the
      extended scaffold, this compound is a potent PSMA inhibitor with an IC50 of 4 nM.
      This siderophore conjugate may be useful for detection of prostate-derived cancer
      cells by magnetic resonance imaging (MRI).

PMID- 18060797
TI  - Determination of gallium by displacement substoichiometric extraction with
      labeled indium-oxinate in chloroform.
AB  - A radiochemical displacement method for the determination of small amounts of
      gallium has been developed. The method involves the displacement of spiked (114m
      In) indium from its oxinate in chloroform. The effects of various ions on the
      extent of displacement have been reported. By this process approximately 6-28
      microg of Ga(III) can be determined. Results are highly reproducible in the
      proposed method.

PMID- 18060798
TI  - On the optimization of the isotopic neutron source method for measuring the
      thermal neutron absorption cross section: advantages and disadvantages of BF3 and
      3He counters.
AB  - The effect of the detector characteristics on the performance of an isotopic
      neutron source device for measuring thermal neutron absorption cross section
      (Sigma) has been examined by means of Monte Carlo simulations. Three specific
      experimental arrangements, alternately with BF(3) counters and (3)He counters of
      the same sizes, have been modelled using the MCNP-4C code. Results of Monte Carlo
      calculations show that devices with BF(3) counters are more sensitive to Sigma,
      but high-pressure (3)He counters offer faster assays.

PMID- 18060799
TI  - A cytokinin receptor homologue is induced during root nodule organogenesis and
      senescence in Lupinus albus L.
AB  - Here we report the isolation of a new cytokinin receptor homologue, LaHK1, from
      lupin (Lupinus albus) root nodules. LaHK1 transcript accumulation was detected in
      different plant organs, and expression was analyzed throughout nodule
      development. We observed notably higher expression in nodule primordia and young
      nodules compared to the root or to mature nodules. We also detected elevated
      transcript accumulation in naturally senescent nodules and in senescent nodules
      subjected to foliar dark stress. The results could be an indication of a putative
      role of this cytokinin receptor homologue in nodule development, from
      morphogenesis through senescence.

PMID- 18060800
TI  - Preferential production of IL-12 by peritoneal macrophages activated by liposomes
      prepared from neoglycolipids containing oligomannose residues.
AB  - The present study demonstrates that liposomes coated with synthesized
      neoglycolipids constructed from mannotriose and
      dipalmitoylphosphatidylethanolamine (Man3-DPPE) activate peritoneal macrophages
      (PEMs) to up-regulate expression of co-stimulatory molecules and preferentially
      secrete IL-12. Injection of Man3-DPPE-coated liposomes (oligomannose-coated
      liposome, OMLs) into the peritoneal cavity of mice resulted in specific and rapid
      incorporation of OMLs into PEMs. Upon OML incorporation, expression of co
      stimulatory molecules, CD40, CD80, and CD86, and of MHC class II molecules was
      clearly enhanced on PEMs. In addition, production of IL-12 from PEMs was clearly
      promoted in response to OML incorporation, while those of IL-1 and IL-6 were
      suppressed. In contrast, liposomes coated with other carbohydrates and those
      without a carbohydrate-coating did not induce production of these cytokines. The
      cytokine profile produced from PEMs in response to OML clearly differed from
      those in response to ligands for TLRs, in which productions of IL-1 and/or IL-6
      were strongly enhanced. Taken together, the results indicate that OMLs activate
      PEMs through a particular type of signal pathway distinct from those activated
      with TLR ligands, leading to specific production of IL-12 and consequent
      maturation of PEMs. Thus, OMLs can be used as a novel adjuvant for efficient
      activation of specific cellular immunity.

PMID- 18060801
TI  - Genetic control of chemokines in severe human internal carotid artery stenosis.
AB  - BACKGROUND AND PURPOSE: Atherosclerosis is an inflammatory disease. Chemokines
      and chemokine receptors are known to be involved in atherogenesis. Common single
      nucleotide polymorphisms (SNPs) affect transcription in response to inflammatory
      stimuli. The aim of this study was to evaluate the correlations between MCP-1,
      RANTES, SDF-1, CCR2, and CCR5 gene polymorphisms with increased risk of internal
      carotid artery (ICA) stenosis. METHODS: Hundred and twelve patients,
      consecutively recruited for ICA occlusive disease, and 282 controls were
      genotyped for MCP-1-2518G, RANTES-403A, CCR5Delta32, CCR2 V64I, and SDF-1-801A
      polymorphisms. RESULTS: The frequency of the SDF-1A allele was significantly
      different between cases and controls: 0.32 vs. 0.20, respectively (OR 1.81; 95%
      CI 1.25-2.60; p=0.007). The frequency of the RANTES-403G allele was significantly
      higher in patients with stenosis >70% (OR, 2.45; 95% CI 1.12-5.71; p=0.015). No
      significant differences were observed with the other polymorphisms. CONCLUSION:
      The reported results seem to correlate the polymorphisms of the genes encoding
      for SDF-1, RANTES with pathogenesis and progression of ICA occlusive disease.
      Although suggestive, these results need confirmation in prospective cross
      sectional studies.

PMID- 18060802
TI  - LPS induces interleukin-6 and interleukin-8 but not tumor necrosis factor-alpha
      in human adipocytes.
AB  - Adipose tissue-derived cytokines are presumably involved in obesity-associated
      pathologies including type 2 diabetes and atherosclerosis. Here we studied the
      lipopolysaccharide (LPS)-induced expression dynamics of tumor necrosis factor
      alpha (TNFalpha), interleukin-6 (IL-6), IL-8 and IL-10 in human adipose tissue
      biopsies, in preadipocyte-derived adipocytes, and in mesenchymal stem cell (MSC)
      derived adipocytes. TNFalpha, IL-6, IL-8 and IL-10 secretions by adipose tissue
      explants were increased 5.5-, 19.5-, 3.5- and 12.5-fold, respectively, by LPS (1
      microg/mL) administration. Concordantly, IL-6 and IL-8 release was dose
      dependently induced in MSC-derived adipocytes by LPS (>10 pg/mL). In contrast,
      TNFalpha and IL-10 remained undetectable even at the highest LPS dose (1
      microg/mL) after 24h. In MSC- and preadipocyte-derived adipocytes, respectively,
      exposure to LPS evoked a weak and transient induction of TNFalpha mRNA whereas
      induction of IL-6 and IL-8 mRNA were pronounced and sustained for at least 24h.
      Basal glucose uptake, lipolysis and IL-6 mRNA were induced by exogenous TNFalpha
      (10 ng/mL) but not by IL-6 (10 ng/mL), IL-8 (100 ng/mL) and IL-10 (20 ng/mL). In
      this adipocyte model TNFalpha induces well known metabolic effects, but together
      with previous reports these data suggest that inflammation-induced TNFalpha may
      derive from non-adipocyte sources in adipose tissue, likely to be macrophages.

PMID- 18060804
TI  - Combined activity of the two Gli2 genes of zebrafish play a major role in
      Hedgehog signaling during zebrafish neurodevelopment.
AB  - It has been proposed that the downstream mediator of the evolutionarily conserved
      Hedgehog pathway Gli2 plays a relatively minor role in neural development of
      zebrafish. The second gli2 of zebrafish, gli2b, is expressed in the neural plate
      and the central nervous system. Our comparative analysis of the developmental
      role of gli2/gli2b demonstrate a major role of the two Gli2s in mediating Hh
      signaling. The Gli2s play an early Hh-independent repressor role in the
      maintenance of neural progenitors and an Hh-dependent activating role during cell
      differentiation in the floor plate, branchial motor neurons, and sensory neurons.
      Our analysis of Gli2b loss-of-function using antisense morpholino
      oligonucleotides indicates that the functions of the two Gli2s diverged in
      evolution. Gli2b acts in cell proliferation and plays an early role in the
      hindbrain within a regulatory cascade involving Notch and Ngn1, as well as a role
      as specific activator in rhombomere 4.

PMID- 18060805
TI  - Disruption of Esrom and Ryk identifies the roof plate boundary as an intermediate
      target for commissure formation.
AB  - Growth cones are guided to their final destination by intermediate targets. Here,
      we identify intermediate targets and signaling components acting on zebrafish
      habenula commissural axons. Live imaging establishes that axons pause at the
      medial habenula before and after crossing the roof plate. esrom mutants axons
      fail to advance beyond the ipsilateral medial habenula. Tsc2 function is reduced
      in mutant axons, indicating cell autonomous defects in signaling. Consistent with
      signaling properties changing outside the roof plate, EphB is surface localized
      on axon segments within a zone demarcated by the medial habenula. wnt4a is
      expressed in the medial habenula and morpholino knockdown causes loss of the
      commissure. Electroporation of truncated Ryk causes axons to reenter the midline
      after reaching the contralateral habenula. These data identify Esrom as a
      mediator of growth cone navigation at an intermediate target and underscore the
      importance of midline boundaries as signaling centers for commissure formation.

PMID- 18060806
TI  - Baculovirus expression and bioactivity of a soluble 140 kDa extracellular
      cleavage fragment of L1 neural cell adhesion molecule.
AB  - L1 neural cell adhesion molecule is the founding member of the L1 subfamily of
      the immunoglobulin superfamily and plays an important role in the overall
      development of both the central and peripheral nervous systems, making it an
      attractive candidate for promoting neural regeneration following injury.
      Currently, L1 used for experimental studies is primarily mammalian-derived;
      however, the insect cell expression system described here provides an alternative
      source of recombinant L1 with equivalent bioactivity. A 140 kDa L1 fragment based
      on a physiological plasmin cleavage site in the extracellular domain was cloned
      and expressed with a C-terminal 6x histidine tag. Recombinant insect cell-derived
      L1 was analyzed by Western blot using an antibody to human L1 to confirm
      immunogenicity and to optimize infection conditions for recombinant L1
      production. The recombinant protein was secreted by insect cells, efficiently
      purified under non-denaturing conditions using dialysis followed by metal
      affinity chromatography, and analyzed by SDS-PAGE to produce a single band of the
      expected approximate 140 kDa size. The bioactivity of insect cell-derived L1 was
      compared to mammalian-derived L1-Fc and poly-L-lysine (PLL) using chick embryonic
      forebrain neurons. The results show comparable, robust neurite outgrowth at 24h
      on insect cell-derived L1 and mammalian-derived L1-Fc, with significantly longer
      neurites than those observed on PLL. Future studies will examine the
      immobilization of L1 to biomaterial surfaces in physiologically appropriate
      orientation via the C-terminal 6x histidine tag and will investigate their
      application in promoting axonal regeneration in the injured nervous system.

PMID- 18060807
TI  - Enhanced innate immune parameters in Labeo rohita (Ham.) following oral
      administration of Bacillus subtilis.
AB  - The present study assessed the use of Bacillus subtilis in fish as a probiotic.
      The bacterium was administered orally at three different doses 0.5 x 10(7)
      (T(2)), 1 x 10(7) (T(3)), 1.5 x 10(7) (T(4)) cfu/g feed to Labeo rohita for two
      weeks. The positive control group (T(1)) and negative control group (T(5,)) were
      fed feed without B. subtilis for the same period. On the 15th day blood and serum
      were sampled to determine respiratory burst activity (NBT assay), differential
      leukocyte counts (DLC) and serum bactericidal activity. Fishes were challenged
      intraperitoneally with Aeromonas hydrophila O:18 after two weeks in the treatment
      groups (T(2), T(3) and T(4)) and also in the positive control group(T(1)), while
      the negative control group (T(5)) was challenged with phosphate buffered saline
      (PBS, pH 7.2) only. The respiratory burst activity and DLC were assessed on the
      3rd day post-challenge. B. subtilis treated fish showed significantly higher
      (P<0.05) respiratory burst activity and bactericidal activity during the pre
      challenge compared with the control groups. The highest respiratory burst
      activity (0.37+/-0.03) and serum bactericidal activity were recorded in the group
      (T(4)) fed feed containing B. subtilis at 1.5 x 10(7)cfu/g feed. Granulocyte
      numbers were significantly higher (P<0.05) in treatment groups in comparison to
      the control in both the pre- and post-challenge periods. The result suggests that
      B. subtilis can enhance certain innate immune responses in rohu.

PMID- 18060808
TI  - High thalamocortical theta coherence in patients with neurogenic pain.
AB  - Patients with severe and chronic neurogenic pain are known to exhibit excess EEG
      oscillations in the 4- to 9-Hz theta frequency band in comparison with healthy
      controls. The generators of these excess EEG oscillations are localized in the
      cortical pain matrix. Since cortex and thalamus are tightly interconnected
      anatomically, we asked how thalamic activity and EEG are functionally related in
      these patients. During the surgical intervention in ten patients with neurogenic
      pain, local field potentials were recorded from the posterior part of the central
      lateral nucleus (CL). The highest thalamocortical coherence was found in the 4-
      to 9-Hz theta frequency band (median 7.7 Hz). The magnitude of thalamocortical
      theta coherence was comparable to the magnitude of EEG coherence between scalp
      electrode pairs. Median thalamocortical theta coherence was 27%, reached up to
      68% and was maximal with frontal midline scalp sites. The observed high
      thalamocortical coherence underlines the importance of the thalamus for the
      synchronization of scalp EEG. We discuss the pathophysiology within the framework
      of a dysrhythmic thalamocortical interplay, which has important consequences for
      the choice of therapeutic strategy in patients with chronic and severe forms of
      neurogenic pain.

PMID- 18060809
TI  - Nonlinear neurobiological probability weighting functions for aversive outcomes.
AB  - While mainstream economic models assume that individuals treat probabilities
      objectively, many people tend to overestimate the likelihood of improbable events
      and underestimate the likelihood of probable events. However, a biological
      account for why probabilities would be treated this way does not yet exist. While
      undergoing fMRI, we presented individuals with a series of lotteries, defined by
      the voltage of an impending cutaneous electric shock and the probability with
      which the shock would be received. During the prospect phase, neural activity
      that tracked the probability of the expected outcome was observed in a
      circumscribed network of brain regions that included the anterior cingulate,
      visual, parietal, and temporal cortices. Most of these regions displayed
      responses to probabilities consistent with nonlinear probability weighting. The
      neural responses to passive lotteries predicted 79% of subsequent decisions when
      individuals were offered choices between different lotteries, and exceeded that
      predicted by behavior alone near the indifference point.

PMID- 18060810
TI  - The development of corpus callosum microstructure and associations with bimanual
      task performance in healthy adolescents.
AB  - Cross-sectional and longitudinal volumetric studies suggest that the corpus
      callosum (CC) continues to mature structurally from infancy to adulthood.
      Diffusion tensor imaging (DTI) provides in vivo information about the directional
      organization of white matter microstructure and shows potential for elucidating
      even more subtle brain changes during adolescent development. We used DTI to
      examine CC microstructure in healthy right-handed adolescents (n=92, ages 9-24
      years) and correlated the imaging data with motor task performance. The primary
      DTI variable was fractional anisotropy (FA), which reflects the degree of white
      matter's directional organization. Participants completed an alternating finger
      tapping test to assess interhemispheric transfer and motor speed. Task
      performance was significantly correlated with age. Analyses of variance indicated
      that 9- to 11-year-olds generally performed worse than each of the older groups.
      Males outperformed females. Significant positive correlations between age and FA
      were observed in the splenium of the CC, which interconnects posterior cortical
      regions. Analyses of variance indicated that individuals older than 18 years had
      significantly higher FA than 9- to 11-year-olds. FA levels in the genu and
      splenium correlated significantly with task performance. Regression analyses
      indicated that bimanual coordination was significantly predicted by age, gender,
      and splenium FA. Decreases in alternating finger tapping time and increases in FA
      likely reflect increased myelination in the CC and more efficient neuronal signal
      transmission. These findings expand upon existing neuroimaging reports of CC
      development by showing associations between bimanual coordination and white
      matter microstructural organization in an adolescent sample.

PMID- 18060811
TI  - Diffusion tensor imaging: structural adaptive smoothing.
AB  - Diffusion Tensor Imaging (DTI) data is characterized by a high noise level. Thus,
      estimation errors of quantities like anisotropy indices or the main diffusion
      direction used for fiber tracking are relatively large and may significantly
      confound the accuracy of DTI in clinical or neuroscience applications. Besides
      pulse sequence optimization, noise reduction by smoothing the data can be pursued
      as a complementary approach to increase the accuracy of DTI. Here, we suggest an
      anisotropic structural adaptive smoothing procedure, which is based on the
      Propagation-Separation method and preserves the structures seen in DTI and their
      different sizes and shapes. It is applied to artificial phantom data and a brain
      scan. We show that this method significantly improves the quality of the estimate
      of the diffusion tensor, by means of both bias and variance reduction, and hence
      enables one either to reduce the number of scans or to enhance the input for
      subsequent analysis such as fiber tracking.

PMID- 18060812
TI  - Probing overtly spoken language at sentential level: a comprehensive high-field
      BOLD-fMRI protocol reflecting everyday language demands.
AB  - Regarding the application of functional magnetic resonance imaging (fMRI) to
      preoperative mapping of language, the majority of previous studies applied silent
      vocalization at word level. Since mapping of language targets the protection of
      overt communication, the selection of the stimulation paradigm is a crucial
      issue. Typically, everyday language demands overt speech with construction of
      syntactically and semantically complete sentences. Here, 23 healthy right-handed
      subjects performed overt vocalization of complete german sentences. Subjects
      produced these sentences based on visually presented semantic choices. Special
      efforts were undertaken to minimize motion artifacts and maximize signal gain on
      a 3-T MR unit. Compared to previous studies, results showed a larger amount of
      highly reliable fMRI activations over the whole brain. Particularly, high
      sensitivity was found for Broca's and Wernicke's regions, as well as anterior and
      inferior temporal areas. Regarding the left hemisphere, simultaneous "Broca" and
      "Wernicke" activities were found in 95% of all subjects. When including atypical
      lateralizations, "Broca" and "Wernicke" activations were found in every subject.
      Overt vocalization at sentential level represents a new comprehensive language
      task with the potential to generate reliable activation maps that reflect brain
      activity associated with everyday language demands.

PMID- 18060813
TI  - Bodyweight gain under pregabalin therapy in epilepsy: mitigation by counseling
      patients?
AB  - OBJECTIVE: To evaluate bodyweight gain during pregabalin therapy for epilepsy and
      the utility of a short counseling program to prevent this side effect. METHODS:
      Randomized controlled trial on the effects of extended versus standard patient
      counseling on the risk of bodyweight gain with 3- and 6-month follow-up including
      a consecutive sample of adult outpatients with epilepsy eligible for pregabalin
      add-on treatment (N=98). RESULTS: The seizure response rate was about 30%, the
      seizure freedom rate was 5% at the 6-month follow-up (intent-to-treat sample,
      N=98). The median bodyweight gain for the according-to-protocol sample (N=62) was
      4.0 kg with no effect of extended counseling. Bodyweight gain was correlated with
      number of anticonvulsant drugs (r=.32, p<.05). CONCLUSIONS: Pregabalin treatment
      is associated with a high risk for bodyweight gain which in part depends on total
      anticonvulsant drug load. This side effect cannot be prevented by extended
      patient counseling within a standard clinical setting.

PMID- 18060814
TI  - Identification and analysis of differentially expressed Heterobasidion parviporum
      genes during natural colonization of Norway spruce stems.
AB  - To identify differentially expressed genes of the white-rot fungus Heterobasidion
      parviporum, two cDNA libraries were constructed using suppressive subtraction
      hybridization (SSH) technique with RNA extracted from an advanced stage of decay
      area and from colonization front next to the reaction zone of the stem of a
      mature Norway spruce naturally colonized by the fungus. Besides several
      cytochrome P450s and hypothetical proteins with unknown function, the SSH
      libraries constructed contained, among others, genes involved in basic cellular
      processes, and lignin and cellulose degradation. To examine the role of selected
      candidate genes for each functional group, three trees, each colonized by a
      different genotype of the pathogen and showing a variable degree of wood decay,
      were used for real-time RT-PCR profiling of candidate genes. In the decay
      transition areas the study revealed activity centers that showed remarkable
      similarity in the transcript profiles of the monitored genes.

PMID- 18060815
TI  - High field 17O solid-state NMR study of alanine tripeptides.
AB  - (17)O chemical shifts of Ala-Ala-Ala, with parallel and anti-parallel beta-sheet
      structures, are observed using a 930-MHz high-resolution solid-state NMR
      spectrometer. Ala-Ala-Ala serves as a model sheet-forming peptide because it can
      be easily prepared as either a parallel or an anti-parallel beta-sheet structure.
      Spectral differences between the two samples are observed which arise from
      molecular packing differences between the two sheet structures. DFT chemical
      shift calculations are performed for the two samples, and the calculated spectra
      are in good agreement with the experimental spectra. The DFT calculations provide
      insight into the nature of the chemical shift differences observed between the
      two sheet structures.

PMID- 18060816
TI  - QSPR models for the physicochemical properties of halogenated methyl-phenyl
      ethers.
AB  - Halogenated methyl-phenyl ethers (anisoles) are ubiquitous organic compounds in
      the environment. In the present study, geometrical optimization and electrostatic
      potential calculations have been performed for 134 halogenated anisoles at the
      HF/6-31G* level of theory. A number of statistically based parameters have been
      obtained. Linear relationships between sub-cooled liquid vapor pressures
      (lgp(L)), n-octanol/water partition coefficient (lgK(ow)) and aqueous
      solubilities (-lgS(w,L)) of halogenated anisoles and the structural descriptors
      have been established by multiple regression method. The result shows that the
      quantities derived from electrostatic potential V(min), V(s,max), summation
      operatorV(s)(+), summation operatorV(s)(-), V(s,av)(-) and nu, together with the
      molecular volume (V(mc)) and E(HOMO) can be well used to express the quantitative
      structure-property relationships of halogenated anisoles, which proves the
      general applicability of this parameter set to a great extent. Good predictive
      capabilities have also been demonstrated. Based on these excellent equations, the
      predicted values have been presented for those halogenated anisoles whose
      experimentally determined physicochemical properties are unavailable.

PMID- 18060817
TI  - The role of collagenases in experimental pulmonary fibrosis.
AB  - Matrix metalloproteinases (MMPs) expression plays a critical role in
      extracellular matrix deposition. Although several pieces of evidence have so far
      indicated that gelatinase contributes to the development of pulmonary fibrosis,
      the role of collagenase remains uncertain. In this study, we attempted to
      determine the role of collagenase using a bleomycin-induced pulmonary fibrosis
      model. Bleomycin was instilled into mice intratracheally. Bronchoalveolar lavage
      fluid (BAL) specimens were analyzed for gelatin and casein zymography, as well as
      by immunoblotting. The histology of the lungs and hydroxyproline contents were
      also assessed. MMPs inhibitor, CGS27023A, was simultaneously orally administered.
      Collagenases were induced in BAL fluids after bleomycin administration based on
      the data of zymography and immunohistochemistry. The co-administration of MMPs
      inhibitor, CGS27023A, with bleomycin resulted in worsening pulmonary fibrosis
      with inhibition of collagenase. The worsening of pulmonary fibrosis was mainly
      induced by CGS27023A administration in the late phase of bleomycin-induced
      pulmonary fibrosis development, but not in the early phase. The present data
      indicated that collagenase plays an anti-fibrotic role in the bleomycin-induced
      pulmonary fibrosis model. Collagenase has a greater effect on fibrosis phase than
      inflammatory phase in the bleomycin-induced pulmonary fibrosis in the mice.

PMID- 18060818
TI  - Melanin-based color variation in the Bearded Vulture suggests a thermoregulatory
      function.
AB  - We document a case of intraspecific variation in plumage colouration in Bearded
      Vultures that may have arisen as a functional response to climate conditions. Two
      subspecies, Gypaetus barbatus barbatus (Eurasia and North Africa populations) and
      Gypaetus barbatus meridionalis (Eastern and Southern Africa), have been described
      on the basis of plumage colour differences. The plumage of G. b. barbatus tends
      to be darker in comparison with that of G. b. meridionalis. The plumage of the
      two subspecies differ in the feathering of the tarsi (more abundant in G. b.
      barbatus) and presence/absence of dark ear tufts (only present in G. b. barbatus,
      and this being the most useful character to distinguish adult specimens of both
      subspecies). When exposing skins under the sun or to electric bulbs in a cold
      room, temperature increases were significantly higher in the black ear tufts than
      in the frontal region of the head, suggesting that the melanized ear patch of G.
      b. barbatus serves, at least, to heat up the air entering the ear channel and
      perhaps also the underlying skin. In addition, G. b. barbatus, which inhabits
      mountainous regions with harsh and long winters, would benefit more from
      feathered tarsi to prevent heat loss through the legs.

PMID- 18060819
TI  - Regulation of AMP-deaminase activity from white muscle of common carp Cyprinus
      carpio.
AB  - AMP-deaminase was purified to electrophoretic homogeneity from white skeletal
      muscle of a teleost fish, the common carp, Cyprinus carpio. The purified enzyme
      was highly stable and showed non-Michaelis-Menten kinetics with a S(0.5) value
      for AMP of 2.52+/-0.16 mM (SEM) and a Hill coefficient of 1.19+/-0.11. Specific
      activity of the purified enzyme was 1000-1200 U/mg protein. The pH optimum was
      6.3 and the enzyme was activated by ADP and ATP, but inhibited by phosphate and
      fluoride. Low concentrations of NaCl and KCl (100-150 mM) activated, whereas
      higher concentrations were inhibitory. Free radicals inactivated the enzyme,
      decreasing V(max) by one-half but not affecting S(0.5) or Hill coefficient.
      Possible regulatory mechanisms of AMP-deaminase activity in fish muscle are
      discussed.

PMID- 18060820
TI  - Outcome and long-term follow-up of 36 patients with tetrahydrobiopterin
      deficiency.
AB  - We describe the treatment, the clinical, and biochemical findings and the outcome
      of 26 patients with 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency and 10
      patients with dihydropteridine reductase (DHPR) deficiency. These are the two
      most common forms of the autosomal-recessively inherited tetrahydrobiopterin
      (BH4) deficiency. Time of diagnosis, dosage of BH4 and neurotransmitter
      precursors, folinic acid substitution, and levels of 5-hydroxyindoleacetic acid
      (5HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF) are essential
      parameters in the follow-up of patients. Unfortunately, treatment protocols vary
      greatly among patients and clinical centers, and CSF investigations and outcome
      assessments are not always available. Seventeen patients with PTPS deficiency and
      four patients with DHPR deficiency were diagnosed within 2 months after birth. In
      14 patients with PTPS deficiency (54%; 9 early and 5 late diagnosed) and 2
      patients with DHPR deficiency (20%; all early diagnosed) no developmental delay
      is observed, while in 10 patients with PTPS deficiency (38%; 6 early and 4 late
      diagnosed) and 8 patients with DHPR deficiency (80%; 2 early and 6 late
      diagnosed) development was delayed. Two PTPS-deficient patients died in the
      newborn period. DHPR deficiency seems to be more severe than PTPS deficiency and
      it is clearly the onset of treatment that determines the outcome. Our data
      suggest that diagnosis within the first month of life is essential for a good
      outcome and that low CSF5 HIAA and HVA values in CSF could be an indicator for
      the ongoing developmental impairment

PMID- 18060821
TI  - Structural insights into the enzymatic mechanism of the pathogenic MAPK
      phosphothreonine lyase.
AB  - The OspF family of phosphothreonine lyase, including SpvC from Salmonella,
      irreversibly inactivates the dual-phosphorylated host MAPKs (pT-X-pY) through
      beta elimination. We determined crystal structures of SpvC and its complex with a
      phosphopeptide substrate. SpvC adopts a unique fold of alpha/beta type. The
      disordered N terminus harbors a canonical D motif for MAPK substrate docking. The
      enzyme-substrate complex structure indicates that recognition of the
      phosphotyrosine followed by insertion of the threonine phosphate into an arginine
      pocket places the phosphothreonine into the enzyme active site. This requires the
      conformational flexibility of pT-X-pY, which suggests that p38 (pT-G-pY) is
      likely the preferred physiological substrate. Structure-based biochemical and
      enzymatic analysis allows us to propose a general acid/base mechanism for beta
      elimination reaction catalyzed by the phosphothreonine lyase. The mechanism
      described here provides a structural understanding of MAPK inactivation by a
      family of pathogenic effectors conserved in plant and animal systems and may also
      open a new route for biological catalysis.

PMID- 18060823
TI  - [Continuing debate on preimplantation genetic diagnosis (PGD)].

PMID- 18060824
TI  - Informing geospatial toolset design: understanding the process of cancer data
      exploration and analysis.
AB  - There is an increasing need for new methods and tools that support knowledge
      construction from complex geospatial datasets related to public health. This
      study is part of a larger effort to develop, implement, and test such methods and
      tools. To be successful, the design of methods and tools must be grounded in a
      solid understanding of the work practices within the domain of use; the research
      reported here focuses on developing that understanding. We adopted a user
      centered approach to toolset design where we investigated the work of cancer
      researchers and used the results of that investigation as inputs into the
      development of design guidelines for new geovisualization and spatial analysis
      tools. Specifically, we conducted key informant interviews focused on use, or
      potential use, of geographic information, methods, and tools and complemented
      this with a systematic analysis of published, peer-reviewed articles on
      geospatial cancer research. Results were used to characterize the typical process
      of analysis, to identify fundamental differences between intensive users of
      geospatial methods and infrequent users, and to outline key stages in analysis
      and tasks within the stages that methods and tools must support. Our findings
      inform design and implementation decisions for visual and analytic tools that
      support cancer prevention and control research and they provide insight into the
      processes used by cancer researchers for addressing the challenges of geographic
      factors in public health research and policy.

PMID- 18060825
TI  - Reshaping the folding energy landscape of human carbonic anhydrase II by a single
      point genetic mutation Pro237His.
AB  - Human carbonic anhydrase (HCA) II participates in a variety of important
      biological processes, and it has long been known that genetic mutations of HCA II
      are closely correlated to human disease. In this research, we investigated the
      effects of a genetic single point mutation P237, which is located on the surface
      of the molecule and does not participate in the HCA II catalysis, on HCA II
      activity, stability and folding. Spectroscopic studies revealed that the mutation
      caused more buried Trp residues to become accessible by solvent and caused the
      NMR signals to become less dispersed, but did not affect the secondary structure
      or the hydrophobic exposure of the protein. The mutant was less stable than the
      wild type enzyme against heat- and GdnHCl-induced inactivation, but its pH
      adaptation was similar to the wild type. The mutation slightly decreased the
      stability of the molten globular intermediate, but gradually affected the
      stability of the native state by a 10-fold reduction of the Gibbs free energy for
      the transition from the native state to the intermediate. This might have led to
      an accumulation of the aggregation-prone molten globular intermediate, which
      further trapped the proteins into the off-pathway aggregates during refolding and
      reduced the levels of active enzyme in vivo. The results herein suggested that
      the correct positioning of the long loop around P237 might be crucial to the
      folding of HCA II, particularly the formation of the active site.

PMID- 18060826
TI  - Potential pathogenic role of beta-amyloid(1-42)-aluminum complex in Alzheimer's
      disease.
AB  - The etiopathogenesis of Alzheimer's disease is far from being clearly understood.
      However, the involvement of metal ions as a potential key factor towards
      conformational modifications and aggregation of amyloid is widely recognized. The
      aim of the present study is to shed some light on the relationship between metal
      ions, amyloid conformation/aggregation, and their potential relationship with the
      conformational aspects of AD. We compare the effects of beta-amyloid(1-42) and
      its various metal complexes (beta-amyloid-Al, beta-amyloid-Zn, beta-amyloid-Cu,
      beta-amyloid-Fe) in human neuroblastoma cells in terms of cell viability,
      membrane structure properties, and cell morphology. No significant toxic effects
      were observed in neuroblastoma cells after 24h treatment both with beta-amyloid
      and beta-amyloid-metals (beta-amyloid-Zn, beta-amyloid-Cu, beta-amyloid-Fe); on
      the other hand, there was a marked reduction of cellular viability after
      treatment with beta-amyloid-Al complex. In addition, treatment with beta-amyloid
      Al increased membrane fluidity much more than other beta-amyloid-metal complexes,
      whose contribution was negligible. Furthermore, the cellular morphology, as
      observed by electron microscopy, was deeply altered by beta-amyloid-Al.
      Importantly, beta-amyloid-Al toxicity is closely and significantly associated
      with a great difference in the structure/aggregation of this complex with respect
      to that of beta-amyloid alone and other beta-amyloid-metal complexes. In
      addition, beta-amyloid, as a consequence of Al binding, becomes strongly
      hydrophobic in character. These findings show a significant involvement of Al,
      compared to the other metal ions used in our experiments, in promoting a specific
      amyloid(1-42) aggregation, which is able to produce marked toxic effects on
      neuroblastoma cells, as clearly demonstrated for the first time in this study.

PMID- 18060827
TI  - 2-D registration and 3-D shape inference of the retinal fundus from fluorescein
      images.
AB  - This study presents methods to 2-D registration of retinal image sequences and 3
      D shape inference from fluorescein images. The Y-feature is a robust geometric
      entity that is largely invariant across modalities as well as across the temporal
      grey level variations induced by the propagation of the dye in the vessels. We
      first present a Y-feature extraction method that finds a set of Y-feature
      candidates using local image gradient information. A gradient-based approach is
      then used to align an articulated model of the Y-feature to the candidates more
      accurately while optimizing a cost function. Using mutual information, fitted Y
      features are subsequently matched across images, including colors and fluorescein
      angiographic frames, for registration. To reconstruct the retinal fundus in 3-D,
      the extracted Y-features are used to estimate the epipolar geometry with a plane
      and-parallax approach. The proposed solution provides a robust estimation of the
      fundamental matrix suitable for plane-like surfaces, such as the retinal fundus.
      The mutual information criterion is used to accurately estimate the dense
      disparity map. Our experimental results validate the proposed method on a set of
      difficult fluorescein image pairs.

PMID- 18060828
TI  - Talk global, act local-patterning the Arabidopsis embryo.
AB  - The primary axis and main tissue types of Arabidopsis are laid down in the early
      embryo. Apical-to-basal auxin flux functions as a global organizer of the axis,
      and recent reports are clarifying our mechanistic understanding of how a graded
      auxin distribution is generated and interpreted. Polar targeting of PIN
      transporters in the cells of the embryo is dynamic and linked to their
      phosphorylation status, suggesting a flexible mechanism for regulating auxin flux
      in space and time. PLETHORA transcription factors then interpret the graded auxin
      distribution to provide positional values along the axis in a dose-dependent
      manner. A comparable framework for tissue patterning in the radial dimension is
      still lacking, although cell surface signaling probably plays a key role.

PMID- 18060829
TI  - Emerging role of cytokinin as a regulator of cellular differentiation.
AB  - Perhaps the most amazing feature of plants is their ability to grow and
      regenerate for years, sometimes even centuries. This fascinating characteristic
      is achieved thanks to the activity of stem cells, which reside in the shoot and
      root apical meristems. Stem cells function as a reserve of undifferentiated cells
      to replace organs and sustain postembryonic plant growth. To maintain meristem
      function, stem cells have to generate new cells at a rate similar to that of
      cells leaving the meristem and differentiating, thus achieving a balance between
      cell division and cell differentiation. Recent findings have improved our
      knowledge on the molecular mechanisms necessary to establish this balance and
      reveal a fundamental signaling role for the plant hormone cytokinin. Evidence has
      been provided to show that in the root meristem cytokinin acts in defined
      developmental domains to control cell differentiation rate, thus controlling root
      meristem size.

PMID- 18060830
TI  - EPR spectra of gamma-irradiated DL-alpha-alanine supported on molecular sieves.
AB  - The aim of the work was to collect information concerning boundary effects which
      are suspected in alpha-alanine dosimeters consisted of powdered microcrystalline
      alpha-alanine and binders. In our experiments the conventional binders were
      replaced by molecular sieves (MS). MS are inorganic porous materials (host
      structures) with well organized and uniform intra-crystalline pore systems of
      nano-scale size. The guest molecules can be either physically adsorbed on very
      large inner MS surface, or chemically bound to the active sites. They can be also
      encapsulated inside the intracrystalline cavities. The EPR spectra of gamma
      irradiated DL-alpha-alanine supported on NaY, CeY, SOD, mordenite, ZSM-5 and
      ALPO(4)-5 were very similar to that one observed for irradiated microcrystalline
      DL-alpha-alanine. In the case of alanine supported on HY an initial EPR spectrum
      was different and only after some weeks it made resemble to the well known
      quintet observed in microcrystalline samples. In sodalites synthesized in the
      presence of DL-alpha-alanine EPR signal appeared in non-irradiated sample was
      very low and structureless. The irradiated sample showed a distinct spectrum
      which was quite different from that one observed for crystalline DL-alpha
      alanine.

PMID- 18060831
TI  - Spectroscopic studies of triethoxysilane sol-gel and coating process.
AB  - Silica sol-gels have been prepared under different conditions using
      triethoxysilane (TES) as precursor. The prepared sol-gels have been used to coat
      aluminum for corrosion protection. Vibrational assignments have been made for
      most vibration bands of TES, TES sol-gel, TES sol-gel-coated aluminum and
      xerogel. It has been noticed that air moisture may have helped the hydrolysis of
      the thin coating films. Xerogels have been obtained from the sol-gel under
      different temperature conditions and the resulting samples have been
      characterized by using infrared and Raman spectroscopic methods. IR data indicate
      that the sol-gel process is incomplete under the ambient conditions although an
      aqueous condition can have slightly improved the process. Two nonequivalent
      silicon atoms have been identified from the collected 29Si NMR spectra for the
      sol-gel, supporting the result derived from the IR data. The frequency of Si-H
      bending vibration has been found to be more sensitive to the skeletal structure
      than that of the Si-H stretching vibration. A higher temperature condition could
      favor the progression of hydrolysis and condensation. A temperature higher than
      300 degrees C would cause sample decomposition without seriously damaging the
      silica network. From infrared intensity measurements and thermo-gravimetric
      analyses, the fractions of incomplete hydrolysis and condensation species have
      been estimated to be 4% and 3%, respectively. Electrochemical data have shown
      that the sol-gel coating significantly improves the corrosion protection
      properties of aluminum.

PMID- 18060832
TI  - Multicomponent kinetic spectrophotometric determination of pefloxacin and
      norfloxacin in pharmaceutical preparations and human plasma samples with the aid
      of chemometrics.
AB  - A spectrophotometric method for the simultaneous determination of the important
      pharmaceuticals, pefloxacin and its structurally similar metabolite, norfloxacin,
      is described for the first time. The analysis is based on the monitoring of a
      kinetic spectrophotometric reaction of the two analytes with potassium
      permanganate as the oxidant. The measurement of the reaction process followed the
      absorbance decrease of potassium permanganate at 526 nm, and the accompanying
      increase of the product, potassium manganate, at 608 nm. It was essential to use
      multivariate calibrations to overcome severe spectral overlaps and similarities
      in reaction kinetics. Calibration curves for the individual analytes showed
      linear relationships over the concentration ranges of 1.0-11.5 mg L(-1) at 526
      and 608 nm for pefloxacin, and 0.15-1.8 mg L(-1) at 526 and 608 nm for
      norfloxacin. Various multivariate calibration models were applied, at the two
      analytical wavelengths, for the simultaneous prediction of the two analytes
      including classical least squares (CLS), principal component regression (PCR),
      partial least squares (PLS), radial basis function-artificial neural network (RBF
      ANN) and principal component-radial basis function-artificial neural network (PC
      RBF-ANN). PLS and PC-RBF-ANN calibrations with the data collected at 526 nm, were
      the preferred methods--%RPE(T) approximately 5, and LODs for pefloxacin and
      norfloxacin of 0.36 and 0.06 mg L(-1), respectively. Then, the proposed method
      was applied successfully for the simultaneous determination of pefloxacin and
      norfloxacin present in pharmaceutical and human plasma samples. The results
      compared well with those from the alternative analysis by HPLC.

PMID- 18060833
TI  - Web-based infectious disease reporting using XML forms.
AB  - OBJECTIVE: Exploring solutions for infectious disease information sharing among
      hospital and public health information systems is imperative to the improvement
      of disease surveillance and emergent response. This paper aimed at developing a
      method to directly transmit real-time data of notifiable infectious diseases from
      hospital information systems to public health information systems on the Internet
      by using a standard eXtensible Markup Language (XML) format. METHODS: The
      mechanism and work flow by which notifiable infectious disease data are created,
      reported and used at health agencies in China was evaluated. The capacity of all
      participating providers to use electronic data interchange to submit transactions
      of data required for the notifiable infectious disease reporting was assessed.
      The minimum data set at national level that is required for reporting for
      national notifiable infectious disease surveillance was determined. The standards
      and techniques available worldwide for electronic health data interchange, such
      as XML, HL7 messaging, CDA and ATSM CCR, etc. were reviewed and compared, and an
      XML implementation format needed for this purpose was defined for hospitals that
      are able to access the Internet to provide a complete infectious disease
      reporting. RESULTS: There are 18,703 county or city hospitals in China. All of
      them have access to basic information infrastructures including computers, e-mail
      and the Internet. Nearly 10,000 hospitals possess hospital information systems
      used for electronically recording, retrieving and manipulating patients'
      information. These systems collect 23 data items required in the minimum data set
      for national notifiable infectious disease reporting. In order to transmit these
      data items to the disease surveillance system and local health information
      systems instantly and without duplication of data input, an XML schema and a set
      of standard data elements were developed to define the content, structure and
      semantics of the data set. These standards make it possible to view and analyse
      the data accurately outside the hospital information systems in many different
      document formats. The paper also identified other issues involved in notifiable
      disease reporting in the future, such as the adoption of approved vocabulary
      standards and implementation problems such as the route, secure transfer,
      parsing, and objective identifying of the XML message. CONCLUSIONS: XML is an
      increasingly important standard for exchange and transmission of data between
      disparate applications and systems. As in its early stages of developing an
      interoperable health information system in China, the XML document structures
      could be a way to exchange the notifiable case information among interest parties
      on the web at present.

PMID- 18060834
TI  - Comparison of vaccine strategies against congenital CMV infection in the guinea
      pig model.
AB  - Vaccines are urgently needed to protect newborns against the devastating sequelae
      of congenital cytomegalovirus infection. Evaluation of candidate vaccines in the
      guinea pig model of congenital infection can shed light on potentially useful
      strategies for humans, since guinea pig CMV (GPCMV) is transmitted to the fetus
      transplacentally, causing infection and disease in utero. A number of vaccine
      strategies have been evaluated in this model, including DNA vaccines, live
      attenuated vaccines, and recombinant glycoprotein vaccines. Induction of virus
      neutralizing antibody appears to play a key role in protection of the fetus.
      Recently, a vectored vaccine based on the GPCMV homolog of the UL83 (pp65)
      protein has also been shown to be effective when used as a preconceptual vaccine
      in this model, suggesting that strategies designed to elicit T-cell responses may
      be of value in protection of the fetus.

PMID- 18060836
TI  - REM sleep behavior disorder and excessive startle reaction to visual stimuli in a
      patient with pontine lesions.

PMID- 18060837
TI  - Supervised moderate intensity exercise improves distance walked at hospital
      discharge following coronary artery bypass graft surgery--a randomised controlled
      trial.
AB  - BACKGROUND: This study aimed to determine whether a structured, inpatient (or
      Phase 1 cardiac rehabilitation), physiotherapy-supervised walking program, with
      or without musculoskeletal and respiratory exercises, might improve walking
      capacity and other parameters for patients undergoing coronary artery bypass
      graft surgery (CABG). METHODS: Ninety-three patients awaiting first-time CABG
      over a 12-month period were randomised to one of three post-operative
      physiotherapy regimens: 'standard intervention', consisting of gentle
      mobilisation; 'walking exercise', consisting of a physiotherapy-supervised,
      moderate intensity walking program; and 'walking/breathing exercise', consisting
      of the same moderate intensity walking program, musculoskeletal exercises and
      respiratory exercises. Primary outcomes; six-minute walking assessment (6MWA)
      distance, vital capacity and health-related quality of life, were measured pre
      operatively, at discharge from hospital and at four weeks following discharge.
      RESULTS: Walking and walking/breathing exercise groups had significantly higher
      6MWA distance (444+/-84 m, 431+/-98 m, respectively) than the standard
      intervention group (377+/-90 m) at discharge from hospital. There was no
      significant difference between intervention groups for 6MWA distance at four-week
      follow-up. There was no significant difference between intervention groups in
      terms of vital capacity and health-related quality of life. CONCLUSIONS: A
      physiotherapy-supervised, moderate intensity walking program in the inpatient
      phase following CABG improves walking capacity at discharge from hospital. The
      performance of respiratory and musculoskeletal exercises confers no additional
      benefit to the measured outcomes.

PMID- 18060838
TI  - Optimal surgical management of descending necrotising mediastinitis: our
      experience and review of literature.
AB  - INTRODUCTION: Descending necrotising mediastinitis is a form of mediastinitis
      caused by odontogenic infection or deep cervical infections, which spreads to the
      mediastinum via the cervical fascial planes. Despite the increased use of CT scan
      as a diagnostic aid and the improvement in antibiotics, mortality in patients
      with descending necrotising mediastinitis remains high, reported between 25 and
      40% in the literature. Surgical management and optimal form of mediastinal
      drainage remain controversial. PATIENTS AND METHODS: We have treated three
      patients with descending necrotising mediastinitis at our institution. Two
      patients were male and one was female with mean age 54.3+/-12.5 years. One of the
      patients was a known diabetic. The primary oropharyngeal infection was Ludwig's
      angina, odontogenic abscess and parapharyngeal abscess. All patients underwent
      mediastinal drainage, one through midsternotomy and two through right thoracotomy
      in addition to cervical drainage. All the three patients had mixed aerobic and
      anaerobic infection. RESULTS: There was no perioperative mortality. Mean ICU stay
      was 32 days (12-53 days). All three patients had septicaemic shock requiring
      prolonged inotropic support. Two patients required tracheostomy because of
      prolonged ventilation. All the patients had recurrent abscesses and collections
      either in neck or in chest requiring drainage either surgically or percutaneously
      under CT scan or ultrasound guidance, thus decreasing the need of repeated
      surgical procedures. CONCLUSION: Descending necrotising mediastinitis is a
      potentially fatal condition. Early diagnosis, prompt surgical drainage,
      monitoring of disease process, appropriate medical management in an intensive
      care unit and a multi-disciplinary approach can significantly reduces the
      mortality in this otherwise fatal condition. Percutaneous drainage of recurrent
      abscesses and collections can decrease the need of repeated surgical procedures
      in these critically ill patients.

PMID- 18060839
TI  - Percutaneous closure of post-myocardial infarction ventricular septal defects: a
      single centre experience.
AB  - BACKGROUND: Ventricular septal defect (VSD) is a serious complication of
      myocardial infarction (MI), occurring in about 0.2% of cases. Untreated,
      mortality in high and early surgical repair is difficult because of friable
      necrotic tissue. Percutaneous closure may be an alternative treatment option in
      selected patients. METHODS: We report our complete single centre experience of
      percutaneous post-MI VSD closure using the Amplatzer device. The VSD was closed
      under general anaesthesia with fluoroscopic and transoesophageal
      echocardiographic guidance. Clinical characteristics and outcomes are reported.
      RESULTS: The five patients were aged from 66 to 76 years. Closure was attempted
      from 1 to 64 days post-MI. VSD closure was performed in two patients after
      surgical patch dehiscence (infero-apical and infero-basal VSDs). The procedure
      was successful in four patients, with failure to cross the interventricular
      septum in one. Thirty-day and 12-month survival was 3/5 (60%); no patient
      undergoing VSD closure early post-MI survived, whereas 3/3 in whom the procedure
      was undertaken >14 days post-MI survived, suggesting that it may be appropriate
      to delay attempts at percutaneous VSD closure after MI. CONCLUSION: Percutaneous
      VSD closure post-MI appears to be a viable alternative to surgical repair, with
      favourable outcomes if it can be undertaken >14 days post-infarct.

PMID- 18060840
TI  - Sternotomy and the beard.
AB  - The presence of a beard or lower facial hair can pose a problem during skin
      preparation, cervical venous line insertion and draping of a patient for a
      sternotomy. We demonstrate how this can be dealt within a simple and economic
      fashion.

PMID- 18060841
TI  - Developing sustainable models of interprofessional learning in practice--the
      TUILIP project.
AB  - This paper will describe the background and development of the Trent Universities
      Interprofessional Learning in Practice Project (TUILIP). It will review some of
      the contributing literature on recent policy initiatives for interprofessional
      learning (IPL) and in particular the literature that supports the case for IPL to
      be embedded in the practice learning environment. The impact of IPL on health
      outcomes is discussed and on team working in practice. The modernisation of the
      National Health Service in the UK is explained and how the East Midlands
      Strategic Health Authority has commissioned the TUILIP project that will promote
      and facilitate the interprofessional skills of students through collaborative
      working within the practice setting. The TUILIP project is described, in
      particular, staff development for practitioners, the centrality of service users
      and the innovative approach of IPL Facilitators in pilot sites across the Trent
      region.

PMID- 18060842
TI  - HIV-1 T-cell vaccines: evaluating the next step.

PMID- 18060843
TI  - Psychometric properties of a Swedish version of the Kansas City Cardiomyopathy
      Questionnaire in a Chronic Heart Failure population.
AB  - BACKGROUND: Valid assessments of health-related Quality of Life (HRQL) are
      increasingly important in chronic, incurable conditions, such as chronic heart
      failure (CHF). AIMS: To evaluate the psychometric properties of a Swedish version
      of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in hospitalized patients
      with decompensated CHF. METHOD AND RESULTS: The KCCQ and SF-36 were administered
      to patients (n=118) with CHF at baseline and then 1 (n=51) and 4 months (n=83)
      after admission. The Swedish version of the KCCQ appears to have acceptable
      convergent and discriminant validity for all suggested health domains. Cronbach's
      alpha and test-retest reliability met for most of the scales the minimum of 0.70.
      Known-groups comparison indicated that the KCCQ discriminated between patients
      differing in the New York Heart Association (NYHA) classification (criterion
      validity). The KCCQ was also more responsive to changes in the NYHA
      classification as compared with the SF-36. However, KCCQ has some weakness in the
      response distributions for two questions and the convergent validity in one
      question. CONCLUSION: Overall, the KCCQ is a valid and reliable instrument in a
      Swedish CHF population. It yields reliable and valid scores and is quite
      responsive to clinical change.

PMID- 18060844
TI  - Incessant donor-to-recipient atrial tachycardia after bilateral lung
      transplantation.

PMID- 18060845
TI  - Autonomic dysfunction in experimental sepsis induced by cecal ligation and
      puncture.
AB  - A systemic inflammatory response to infection characterizes sepsis which
      associated to refractory hypotension, turns into severe sepsis. Our aim was to
      evaluate hormonal and cardiovascular alterations after experimental sepsis
      induced by cecal ligation and puncture (CLP). Male Wistar rats (200-250 g) were
      submitted to CLP or sham operation. The animals were decapitated at 0, 2, 4, 6
      and 8 h after surgery for collection of blood samples for plasma osmolality,
      sodium and vasopressin (AVP) measurements. The mean arterial pressure (MAP) and
      heart rate (HR) were recorded 1 h before and to each 1 h during 5hs after
      surgery. The spontaneous baroreflex sensitivity and spectral analysis of HR and
      MAP variability were analyzed after recording. The plasma osmolality and sodium
      did not show any alterations compared to the sham group. MAP decreased from 3 h
      (85 vs.103 mm Hg, P<0.05) to 5 h in the CLP group (76 vs.106 mm Hg, P<0.05). This
      was accompanied by an increase in HR. The AVP plasma level was elevated at 4 h
      (6.0+/-1.1 vs. 1.1+/-0.2 pg/mL, P<0.05) and returned to basal levels at 8 h after
      CLP (2.3+/-0.5 vs. 1.9+/-0.2 pg/mL, P>0.05). A reduction in baroreflex
      sensitivity occurred 1 h after injury. The CLP group showed a reduction in
      overall variability, low-frequency power, and low/high-frequency ratio of HR and
      low-frequency power of MAP. The data suggest an impairment of autonomic control
      of the heart and vessels during polymicrobial sepsis. This reduction in autonomic
      nervous system activity causes the impairment of baroreflex that in turn may
      contribute to the reduction of vasopressin plasma levels in the late phase of
      severe sepsis.

PMID- 18060846
TI  - Gene expression analysis in post-embryonic pericardial cells of Drosophila.
AB  - Increasing evidence suggests conservation of cardiovascular molecules between
      vertebrates and invertebrates. Vertebrate Rudhira, an evolutionary conserved WD40
      protein is expressed during primitive erythropoiesis, neoangiogenesis and tumors.
      We report here the expression profile of the Drosophila ortholog of Rudhira
      (DRudh) in the fly life cycle. DRudh is expressed specifically in all post
      embryonic pericardial cells (PCs) and garland cells (GCs). This is the first
      report of a cytoplasmic marker highly specific to post-embryonic PCs. Embryonic
      PCs belong to three distinct genetic classes based on Odd-skipped (Odd), Even
      skipped (Eve) and Tinman (Tin) expression. To identify which among these three
      classes of PCs expresses DRudh in post-embryonic stages, we analyzed expression
      of embryonic PC markers in the post-embryonic stages. Unlike in the embryo all
      larval PCs show an identical gene expression profile. While Odd and Eve
      expression is mutually exclusive in the embryonic PCs, these two markers are co
      expressed in larval PCs but show a distinct subcellular localization. Tin is not
      expressed in any post-embryonic PC. Additionally larval PCs also express the GATA
      factor, Serpent (Srp) and the extracellular matrix protein, Pericardin (Prc).
      While PC number is known to decrease post-embryogenesis, which of the Odd or Eve
      lineage embryonic PCs persists is not known. Co-expression of the two distinct
      lineage markers only in post-embryonic stages indicates a complex temporal
      regulation of gene expression in PCs.

PMID- 18060847
TI  - Rapid method for the quantification of amoxicillin and its major metabolites in
      pig tissues by liquid chromatography-tandem mass spectrometry with emphasis on
      stability issues.
AB  - A fast method for the quantitative determination of amoxicillin (AMO),
      amoxicilloic acid (AMA) and amoxicillin diketopiperazine-2',5'-dione (DIKETO) in
      pig edible tissues (kidney, liver, fat and muscle) with liquid chromatography
      tandem mass spectrometry (LC-ESI-MS/MS) is presented. The method uses a simple
      liquid-liquid extraction of the tissue matrix with a 10 mM potassium dihydrogen
      phosphate buffer (pH 4.5) as extraction solvent. After deproteinisation by
      ultrafiltration, the tissue extract was directly injected onto the LC column.
      Chromatographic separation of the components was performed on a PLRP-S polymeric
      column using 0.1% of formic acid in water and acetonitrile. The mass spectrometer
      was operated in the positive electrospray MS/MS mode. The method was fully
      validated according to EU requirements (linearity, precision, trueness,
      quantification limit, detection limit and specificity). The stability of the
      components was evaluated over the pH range from 1.2 to 8.0. Biological samples of
      pigs medicated with AMO and AMO/clavulanic acid were analyzed using the developed
      method.

PMID- 18060848
TI  - Generational effects and gender height dimorphism in contemporary Spain.
AB  - We examine the influence of socio-environmental (and birth cohort specific)
      effects on both adult height and gender dimorphism (height gap). Our data set is
      from contemporary Spain, a country governed by an authoritarian regime for about
      40 years. Both OLS and quantile regression approaches are used to examine these
      patterns. Furthermore, we then draw upon a Blinder-Oaxaca decomposition approach
      to explain the influence of socio-political environment in explaining gender
      dimorphism. Our findings point to a significant increase in adult height in the
      generations that benefited from the country's economic liberalization in the
      1950s, and especially among those brought up after the transition to democracy in
      the 1970s. In contrast, individual heterogeneity suggests that only in recent
      generations has "height increased more among the tallest". We also find that the
      effects of education on height are greater among shorter individuals. Although
      the mean gender difference in height is 11.7cm, birth cohort and capabilities
      effects along with other controls explain on average roughly 4% of the gender
      height dimorphism, irrespective of the quantile considered.

PMID- 18060849
TI  - Excimer laser channel creation in polyethersulfone hollow fibers for
      compartmentalized in vitro neuronal cell culture scaffolds.
AB  - Hollow fiber scaffolds that compartmentalize axonal processes from their cell
      bodies can enable neuronal cultures with directed neurite outgrowth within a
      three-dimensional (3-D) space for controlling neuronal cell networking in vitro.
      Controllable 3-D neuronal networks in vitro could provide tools for studying
      neurobiological events. In order to create such a scaffold, polyethersulfone
      (PES) microporous hollow fibers were ablated with a KrF excimer laser to generate
      specifically designed channels for directing neurite outgrowth into the luminal
      compartments of the fibers. Excimer laser modification is demonstrated as a
      reproducible method to generate 5microm diameter channels within PES hollow fiber
      walls that allow compartmentalization of neuronal cell bodies from their axons.
      Laser modification of counterpart flat sheet PES membranes with peak surface
      fluences of 1.2Jcm(-2) results in increased hydrophobicity and laminin adsorption
      on the surface compared with the unmodified PES surface. This is correlated to
      enhanced PC12 cell adhesion with increasing fluence onto laser-modified PES
      membrane surfaces coated with laminin when compared with unmodified surfaces.
      Adult rat neural progenitor cells differentiated on PES fibers with laser-created
      channels resulted in spontaneous cell process growth into the channels of the
      scaffold wall while preventing entrance of cell bodies. Therefore, laser-modified
      PES fibers serve as scaffolds with channels conducive to directing neuronal cell
      process growth. These hollow fiber scaffolds can potentially be used in
      combination with perfusion and oxygenation hollow fiber membrane sets to
      construct a hollow fiber-based 3-D bioreactor for controlling and studying in
      vitro neuronal networking in three dimensions between compartmentalized cultures.

PMID- 18060850
TI  - Evaluation of near infrared spectroscopy in monitoring postoperative regional
      tissue oxygen saturation for fibular flaps.
AB  - The ability of near infrared spectroscopy (NIRS) to predict vascular compromise
      in vascular free flaps postoperatively has been assessed, and the extent of
      regional tissue oxygen saturation (rSO(2)) after fibular flap transplantation was
      investigated quantitatively. To validate the sensibility and precision of the
      technique, the following methods were used. (1) Forearm vessel obstructive tests
      were conducted in four healthy volunteers. (2) Measurement and analysis of
      bilateral rSO(2) at the mandibular body and ramus were performed in 40 healthy
      volunteers by NIRS in the morning and afternoon. (3) Measurement and analysis of
      rSO(2) in transplanted fibular flaps for 41 cases with mandibular reconstruction
      were performed by NIRS at postoperative days 1-6. The results were: NIRS had high
      sensibility and precision in monitoring rSO(2) of living tissues. No significant
      difference in the values of rSO(2) was found across different times or areas in
      the normal mandible. However, rSO(2) in the transplanted fibular flaps was
      reduced compared to the value on the control side. rSO(2) decreased gradually 4
      12 hours postoperatively. After that period, rSO(2) increased gradually and
      approached the value of the control side at 20 h after the operation. It can be
      concluded that NIRS is a reliable noninvasive method for monitoring blood
      circulation in transplanted tissues, particularly for buried flaps.

PMID- 18060851
TI  - Large cystic tumour at the chest wall mimicking an echinococcosis: a case report.
AB  - The authors report an atypical late onset of a big axillary lymphatic
      malformation in a 41-year-old male. Considering the patient's history and
      clinical findings at first presentation, the swelling was highly suspicious for
      malignancy or cystic echinococcosis. A consequent CT showed non infiltrative
      growth with inhomogeneous density but remained non conclusive regarding
      diagnosis. Subsequently incision biopsy revealed lymphatic tissue and raised
      suspicion for lymphatic malformation. The tumour was excised completely and
      showed no recurrence in a 1-year follow up. Late onset lymphatic malformations
      can mimic malignant tumours or other rare conditions such as echinococcosis which
      has to be taken into consideration as differential diagnosis especially in known
      areas of hydatid diseases.

PMID- 18060852
TI  - Purification and characterization of the wild type and truncated human
      cystathionine beta-synthase enzymes expressed in E. coli.
AB  - In this paper, we describe the expression and characterization of recombinant
      human cystathionine beta-synthase (CBS) in Escherichia coli. We have used a
      glutathione-S-transferase (GST) fusion protein vector and incorporated a cleavage
      site with a long hinge region which allows for the independent folding of CBS and
      its fusion partner. In addition, our construct has the added benefit of yielding
      a purified CBS which only contains one extra glycine amino acid residue at the N
      terminus. In our two-step purification procedure we are able to obtain a highly
      pure enzyme in sufficient quantities for crystallography and other physical
      chemical methods. We have investigated the biochemical and catalytic properties
      of purified full-length human CBS and of two truncation mutants lacking the C
      terminal domain or both the N-terminal heme-binding and the C-terminal regulatory
      regions. Specifically, we have determined the pH optima of the different CBS
      forms and their kinetic and spectral properties. The full-length and the C
      terminally truncated enzyme had a broad pH 8.5 optimum while the pH optimum of
      the N- and C- terminally truncated enzyme was sharp and shifted to pH 9.
      Furthermore, we have shown unequivocally that CBS binds one mole of heme per
      subunit by determining both the heme and the iron content of the enzyme. The
      activity of the enzyme was unaffected by the redox status of the heme iron.
      Finally, we show that CBS is stimulated by S-adenosyl- l-methionine but not its
      analogs.

PMID- 18060853
TI  - Prostaglandin E2 inhibits tumor necrosis factor-alpha RNA through PKA type I.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that may contribute to the
      pathogenesis of septic shock, rheumatoid arthritis, cancer, and diabetes.
      Prostaglandins endogenously produced by macrophages act in an autocrine fashion
      to limit TNF-alpha production. We investigated the timing and signaling pathway
      of prostaglandin-mediated inhibition of TNF-alpha production in Raw 264.7 and
      J774 macrophages. TNF-alpha mRNA levels were rapidly modulated by PGE(2) or
      carbaprostacylin. PGE(2) or carbaprostacyclin prevented and rapidly terminated on
      going TNF-alpha gene transcription within 15 min of prostaglandin treatment.
      Selective activation of PKA type I, but not PKA type II or Epac, with chemical
      analogs of cAMP was sufficient to inhibit LPS-induced TNF-alpha mRNA levels. The
      mechanisms by which prostaglandins limit TNF-alpha mRNA levels may underlie
      endogenous regulatory mechanisms that limit inflammation, and may have important
      implications for understanding chronic inflammatory disease pathogenesis.

PMID- 18060854
TI  - Adipogenesis of bovine perimuscular preadipocytes.
AB  - In this study, non-transformed progeny adipofibroblasts, derived from mature
      adipocyte dedifferentiation, was used as a novel in vitro model to study
      adipogenic gene expression in cattle. Adipofibroblasts from dedifferentiated
      mature perimuscular fat (PMF) tissue were cultured with differentiation
      stimulants until the cells exhibited morphological differentiation. Treated cells
      were harvested from day 2 to 16 for RNA extraction, whereas control cells were
      cultured without addition of stimulants. Results from time course gene expression
      assays by quantitative real-time PCR revealed that peroxisome proliferator
      activated receptor gamma (PPAR-gamma), sterol regulatory element binding protein
      1 (SREBP-1) and their six down-stream genes were co-expressed at day 2 post
      differentiation induction. When compared to other adipogenesis culture systems,
      the adipogenic gene expression of bovine PMF adipofibroblasts culture was
      different, especially to the rodent model. Collectively, these results
      demonstrated PPAR-gamma and SREBP-1 cooperatively play a key role to regulate the
      re-differentiation of bovine adipofibroblasts, during early conversion stages in
      vitro.

PMID- 18060855
TI  - Citrus auraptene acts as an agonist for PPARs and enhances adiponectin production
      and MCP-1 reduction in 3T3-L1 adipocytes.
AB  - Citrus fruit compounds have many health-enhancing effects. In this study, using a
      luciferase ligand assay system, we showed that citrus auraptene activates
      peroxisome proliferator-activated receptor (PPAR)-alpha and PPARgamma. Auraptene
      induced up-regulation of adiponectin expression and increased the ratio of the
      amount of high-molecular-weight multimers of adiponectin to the total
      adiponectin. In contrast, auraptene suppressed monocyte chemoattractant protein
      (MCP)-1 expression in 3T3-L1 adipocytes. Experiments using PPARgamma antagonist
      demonstrated that these effects on regulation of adiponectin and MCP-1 expression
      were caused by PPARgamma activations. The results indicate that auraptene
      activates PPARgamma in adipocytes to control adipocytekines such as adiponectin
      and MCP-1 and suggest that the consumption of citrus fruits, which contain
      auraptene can lead to a partial prevention of lipid and glucose metabolism
      abnormalities.

PMID- 18060856
TI  - Enzymatic synthesis of dimaltosyl-beta-cyclodextrin via a transglycosylation
      reaction using TreX, a Sulfolobus solfataricus P2 debranching enzyme.
AB  - Di-O-alpha-maltosyl-beta-cyclodextrin ((G2)(2)-beta-CD) was synthesized from 6-O
      alpha-maltosyl-beta-cyclodextrin (G2-beta-CD) via a transglycosylation reaction
      catalyzed by TreX, a debranching enzyme from Sulfolobus solfataricus P2. TreX
      showed no activity toward glucosyl-beta-CD, but a transfer product (1) was
      detected when the enzyme was incubated with maltosyl-beta-CD, indicating
      specificity for a branched glucosyl chain bigger than DP2. Analysis of the
      structure of the transfer product (1) using MALDI-TOF/MS and isoamylase or
      glucoamylase treatment revealed it to be dimaltosyl-beta-CD, suggesting that TreX
      transferred the maltosyl residue of a G2-beta-CD to another molecule of G2-beta
      CD by forming an alpha-1,6-glucosidic linkage. When [(14)C]-maltose and maltosyl
      beta-CD were reacted with the enzyme, the radiogram showed no labeled dimaltosyl
      beta-CD; no condensation product between the two substrates was detected,
      indicating that the synthesis of dimaltosyl-beta-CD occurred exclusively via
      transglycosylation of an alpha-1,6-glucosidic linkage. Based on the HPLC elution
      profile, the transfer product (1) was identified to be isomers of 6(1),6(3)- and
      6(1),6(4)-dimaltosyl-beta-CD. Inhibition studies with beta-CD on the
      transglycosylation activity revealed that beta-CD was a mixed-type inhibitor,
      with a K(i) value of 55.6 micromol/mL. Thus, dimaltosyl-beta-CD can be more
      efficiently synthesized by a transglycosylation reaction with TreX in the absence
      of beta-CD. Our findings suggest that the high yield of (G2)(2)-beta-CD from G2
      beta-CD was based on both the transglycosylation action mode and elimination of
      the inhibitory effect of beta-CD.

PMID- 18060857
TI  - Functional grouping of osteoclast genes revealed through microarray analysis.
AB  - We describe for the first time functional clusters of genes that are modulated
      during the differentiation of osteoclasts. Pathway analysis was applied to gene
      array data generated from affymetrix chips hybridized to RNA isolated from
      RAW264.7 cells exposed to RANK-ligand (RANK-L) for 5 days. This analysis revealed
      major functional gene clusters that were either up- or down-regulated during
      osteoclastogenesis. Some of the genes within the clusters have known functions,
      while others do not. We discuss herein the relevance of these functional gene
      clusters and their modulation to biological processes underlying the formation,
      function, and fate of osteoclasts.

PMID- 18060858
TI  - Neurofilament protein aggregation in a cell line model system.
AB  - Protein aggregates are associated with many diseases and even aggregates of
      proteins that have no role in disease are inherently toxic to both neuronal and
      non-neuronal cells. We have developed a model system to explore the mechanism of
      protein aggregation using a mouse muscle cell line expressing chimeric
      neurofilament (NF) proteins, a constituent of the protein aggregates in ALS, Lewy
      body dementia, and Charcot-Marie-Tooth disease. Formation of protein aggregates
      in these cells leads to reduced cell viability and activated caspases. Aggregates
      contained both chimeric NF proteins and ubiquitin by immunolocalization and were
      predominately cytosolic when proteins were expressed at low levels or for shorter
      periods of time but were present in the nucleus when expression levels increased.
      This system represents a flexible, new tool to decipher the molecular mechanism
      of protein aggregation and the contributions of aggregation to cell toxicity.

PMID- 18060859
TI  - Comparative proteomic and transcriptomic profiling of the human hepatocellular
      carcinoma.
AB  - Proteome analysis of human hepatocellular carcinoma (HCC) was done using two
      dimensional difference gel electrophoresis. To gain an understanding of the
      molecular events accompanying HCC development, we compared the protein expression
      profiles of HCC and non-HCC tissue from 14 patients to the mRNA expression
      profiles of the same samples made from a cDNA microarray. A total of 125 proteins
      were identified, and the expression profiles of 93 proteins (149 spots) were
      compared to the mRNA expression profiles. The overall protein expression ratios
      correlated well with the mRNA ratios between HCC and non-HCC (Pearson's
      correlation coefficient: r=0.73). Particularly, the HCC/non-HCC expression ratios
      of proteins involved in metabolic processes showed significant correlation to
      those of mRNA (r=0.9). A considerable number of proteins were expressed as
      multiple spots. Among them, several proteins showed spot-to-spot differences in
      expression level and their expression ratios between HCC and non-HCC poorly
      correlated to mRNA ratios. Such multi-spotted proteins might arise as a
      consequence of post-translational modifications.

PMID- 18060860
TI  - Atrazine binds to F1F0-ATP synthase and inhibits mitochondrial function in sperm.
AB  - Atrazine is a widely used triazine herbicide. Although controversy still exists,
      a number of recent studies have described its adverse effects on various animals
      including humans. Of particular interest is its effects on reproductive capacity.
      In this study, we investigated the mechanisms underlying the adverse effects of
      atrazine, with a focus on its effects on sperm. Here we show evidence that
      mitochondrial F(1)F(0)-ATP synthase is a molecular target of atrazine. A series
      of experiments with sperm and isolated mitochondria suggest that atrazine
      inhibits mitochondrial function through F(1)F(0)-ATP synthase. Moreover, affinity
      purification using atrazine as a ligand demonstrates that F(1)F(0)-ATP synthase
      is a major atrazine-binding protein in cells. The inhibitory activity against
      mitochondria and F(1)F(0)-ATP synthase is not limited to atrazine but is likely
      to be applicable to other triazine-based compounds. Thus, our findings may have
      wide relevance to pharmacology and toxicology.

PMID- 18060861
TI  - Gene expression patterns of bovine perimuscular preadipocytes during
      adipogenesis.
AB  - Bovine perimuscular fat (PMF) preadipocytes were induced to undergo adipogenesis
      in vitro in our recent study to define the expression patterns of genes involved
      in the differentiation process. Based on the understanding of the interaction
      among adipogenic genes, a broad overview of gene expression profile in the
      differentiating PMF preadipocytes was evaluated using bovine specific DNA
      microarray from day 2 to 8 post-differentiation induction. A total of 100
      significantly differentially expressed genes were detected between differentiated
      and control cells including those involved in several biochemical pathways and
      cellular/molecular signaling. In addition, quantitative real-time PCR validated
      that typical adipogenic genes were up-regulated at early differentiation in the
      preadipocytes. These results suggest that the PMF preadipocyte system is
      available as a novel in vitro model for molecular adipogenesis studies in the
      bovine and that a series of genes are switched on/off during early events
      associated with adipogenesis.

PMID- 18060862
TI  - CD200: a putative therapeutic target in cancer.
AB  - CD200 was recently described as a new prognosis factor in multiple myeloma and
      acute myeloid leukemia. CD200 is a membrane glycoprotein that imparts an
      immunoregulatory signal through CD200R, leading to the suppression of T-cell
      mediated immune responses. We investigated the expression of CD200 in cancer
      using publicly available gene expression data. CD200 gene expression in normal or
      malignant human tissues or cell lines was obtained from the Oncomine Cancer
      Microarray database, Amazonia database and the ITTACA database. We found
      significant overexpression of CD200 in renal carcinoma, head and neck carcinoma,
      testicular cancer, malignant mesothelioma, colon carcinoma, MGUS/smoldering
      myeloma, and in chronic lymphocytic leukemia compared to their normal cells or
      their tissue counterparts. Moreover, we show that CD200 expression is associated
      with tumor progression in various cancers. Taken together, these data suggest
      that CD200 is a potential therapeutic target and prognostic factor for a large
      array of malignancies.

PMID- 18060863
TI  - The B2 alternatively spliced isoform of nonmuscle myosin II-B lacks actin
      activated MgATPase activity and in vitro motility.
AB  - We report the initial biochemical characterization of an alternatively spliced
      isoform of nonmuscle heavy meromyosin (HMM) II-B2 and compare it with HMM II-B0,
      the nonspliced isoform. HMM II-B2 is the HMM derivative of an alternatively
      spliced isoform of endogenous nonmuscle myosin (NM) II-B, which has 21-amino
      acids inserted into loop 2, near the actin-binding region. NM II-B2 is expressed
      in the Purkinje cells of the cerebellum as well as in other neuronal cells [X.
      Ma, S. Kawamoto, J. Uribe, R.S. Adelstein, Function of the neuron-specific
      alternatively spliced isoforms of nonmuscle myosin II-B during mouse brain
      development, Mol. Biol. Cell 15 (2006) 2138-2149]. In contrast to any of the
      previously described isoforms of NM II (II-A, II-B0, II-B1, II-C0 and II-C1) or
      to smooth muscle myosin, the actin-activated MgATPase activity of HMM II-B2 is
      not significantly increased from a low, basal level by phosphorylation of the
      20kDa myosin light chain (MLC-20). Moreover, although HMM II-B2 can bind to actin
      in the absence of ATP and is released in its presence, it cannot propel actin in
      the sliding actin filament assay following MLC-20 phosphorylation. Unlike HMM II
      B2, the actin-activated MgATPase activity of a chimeric HMM with the 21-amino
      acid II-B2 sequence inserted into the homologous location in the heavy chain of
      HMM II-C is increased following MLC-20 phosphorylation. This indicates that the
      effect of the II-B2 insert is myosin heavy chain specific.

PMID- 18060864
TI  - Adenosine A(2B) receptor mediates an increase on VEGF-A production in rat kidney
      glomeruli.
AB  - Up-regulation of the glomerular expression and the activity of vascular
      endothelial growth factor-A (VEGF) have been identified as an early pathogenic
      event for the progression of diabetic nephropathy. Currently, however the
      mediators are not yet clearly recognized. In this study we identified all four
      adenosine receptor (AR) subtypes, i.e. A(1), A(2A), A(2B) and A(3) in isolated
      rat kidney glomeruli. We localized the expression of A(2B)AR in podocytes, the
      primary VEGF producing cells. The ex vivo treatment of kidney glomeruli with
      adenosine or a general AR agonist NECA, increases VEGF protein content. In
      addition, NECA treatment elicits VEGF release. These effects were blocked by the
      A(2B)AR selective antagonist MRS1754 supplementation. Furthermore, we showed that
      A(2B)AR activation was necessary to promote a higher expression of VEGF in kidney
      glomeruli upon exposure to high d-glucose concentration, a pathogenic condition
      like those observed in diabetic nephropathy.

PMID- 18060865
TI  - Calcium and cargoes as regulators of myosin 5a activity.
AB  - Myosin 5a is a two-headed actin-dependent motor that transports various cargoes
      in cells. Its enzymology and mechanochemistry have been extensively studied in
      vitro. It is a processive motor that takes multiple 36nm steps on actin. The
      enzymatic activity of myosin 5 is regulated by an intramolecular folding
      mechanism whereby its lever arms fold back against the coiled-coil tail such that
      the motor domains directly bind the globular tail domains. We show that the
      structure seen in individual folded molecules is consistent with electron density
      map of two-dimensional crystals of the molecule. In this compact state, the actin
      activated MgATPase activity of the molecule is markedly inhibited and the
      molecule cannot move processively on surface bound actin filaments. The actin
      activated MgATPase activity of myosin 5a is activated by increasing the calcium
      concentration or by binding of a cargo-receptor molecule, melanophilin, in vitro.
      However, calcium binding to the calmodulin light chains results in dissociation
      of some of the calmodulin which disrupts the ability of myosin 5a to move on
      actin filaments in vitro. Thus we propose that the physiologically relevant
      activation pathway in vivo involves binding of cargo-receptor proteins.

PMID- 18060866
TI  - ADP-ribosylation factor arf6p may function as a molecular switch of new end take
      off in fission yeast.
AB  - Small GTPases act as molecular switches in a wide variety of cellular processes.
      In fission yeast Schizosaccharomyces pombe, the directions of cell growth change
      from a monopolar manner to a bipolar manner, which is known as 'New End Take Off'
      (NETO). Here I report the identification of a gene, arf6(+), encoding an ADP
      ribosylation factor small GTPase, that may be essential for NETO. arf6Delta cells
      completely fail to undergo NETO. arf6p localizes at both cell ends and
      presumptive septa in a cell-cycle dependent manner. And its polarized
      localization is not dependent on microtubules, actin cytoskeletons and some NETO
      factors (bud6p, for3p, tea1p, tea3p, and tea4p). Notably, overexpression of a
      fast GDP/GTP-cycling mutant of arf6p can advance the timing of NETO. These
      findings suggest that arf6p functions as a molecular switch for the activation of
      NETO in fission yeast.

PMID- 18060867
TI  - Proteomic analysis of pancreas derived from adult cloned pig.
AB  - The potential medical applications of animal cloning include xenotransplantation,
      but the complex molecular cascades that control porcine organ development are not
      fully understood. Still, it has become apparent that organs derived from cloned
      pigs may be suitable for transplantation into humans. In this study, we examined
      the pancreas of an adult cloned pig developed through somatic cell nuclear
      transfer (SCNT) using two-dimensional electrophoresis (2-DE) and Western
      blotting. Proteomic analysis revealed 69 differentially regulated proteins,
      including such apoptosis-related species as annexins, lamins, and heat shock
      proteins, which were unanimously upregulated in the SCNT sample. Among the
      downregulated proteins in SCNT pancreas were peroxiredoxins and catalase. Western
      blot results indicate that several antioxidant enzymes and the anti-apoptotic
      protein were downregulated in SCNT pancreas, whereas several caspases were
      upregulated. Together, these data suggest that the accumulation of reactive
      oxygen species (ROS) in the pancreas of an adult cloned pig leads to apoptosis.

PMID- 18060868
TI  - A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor
      associated with KAP-1.
AB  - The Kruppel-associated box (KRAB)-containing zinc finger proteins (ZFPs) comprise
      the largest family of zinc finger transcription factors that function as
      transcriptional repressors. In the study of glial cell line-derived neurotrophic
      factor (GDNF)-RET signaling, we have identified bone marrow zinc finger 3
      (BMZF3), encoding a KRAB-ZFP, as a GDNF-inducible gene by differential display
      analysis. The expression of BMZF3 transcripts in the human neuroblastoma cell
      line TGW increased 1h after GDNF stimulation, as determined by Northern blotting
      and quantitative reverse-transcriptase polymerase chain reaction. The BMZF3
      possesses transcriptional repressor activity in the KRAB domain. BMZF3 interacts
      with a co-repressor protein, KRAB-associated protein 1 (KAP-1), through the KRAB
      domain and siRNA-mediated knockdown of KAP-1 abolished the transcriptional
      repressor activity of BMZF3, indicating that KAP-1 is necessary for BMZF3
      function. Furthermore, siRNA-mediated silencing of BMZF3 inhibited cell
      proliferation. These findings suggest that BMZF3 is a transcriptional repressor
      induced by GDNF that plays a role in cell proliferation.

PMID- 18060869
TI  - Lysyl oxidase propeptide inhibits smooth muscle cell signaling and proliferation.
AB  - Lysyl oxidase is required for the normal biosynthesis and maturation of collagen
      and elastin. It is expressed by vascular smooth muscle cells, and its increased
      expression has been previously found in atherosclerosis and in models of balloon
      angioplasty. The lysyl oxidase propeptide (LOX-PP) has more recently been found
      to have biological activity as a tumor suppressor, and it inhibits Erk1/2 Map
      kinase activation. We reasoned that LOX-PP may have functions in normal non
      transformed cells. We, therefore, investigated its effects on smooth muscle
      cells, focusing on important biological processes mediated by Erk1/2-dependent
      signaling pathways including proliferation and matrix metalloproteinase-9 (MMP-9)
      expression. In addition, we investigated whether evidence for accumulation of LOX
      PP could be found in vivo in a femoral artery injury model. Recombinant LOX-PP
      was expressed and purified, and was found to inhibit primary rat aorta smooth
      muscle cell proliferation and DNA synthesis by more than 50%. TNF-alpha
      stimulated MMP-9 expression and Erk1/2 activation were both significantly
      inhibited by LOX-PP. Immunohistochemistry studies carried out with affinity
      purified anti-LOX-PP antibody showed that LOX-PP epitopes were expressed at
      elevated levels in vascular lesions of injured arteries. These novel data suggest
      that LOX-PP may provide a feedback control mechanism that serves to inhibit
      properties associated with the development of vascular pathology.

PMID- 18060870
TI  - Transforming growth factor-beta enables NFATc1 expression during
      osteoclastogenesis.
AB  - Osteoclastogenesis is dependent on distinct stimuli that prime and activate
      osteoclast differentiation. One cytokine needed to prime monocytes for
      osteoclastogenesis is TGF-beta, which enables and augments RANKL and TNF-alpha
      induced osteoclast differentiation. However, the precise time-period during which
      this occurs and the molecular mechanism mediating this action are unknown. We
      report here TGF-beta prime monocytes for osteoclast formation within 24h by
      regulating expression of NFATc1, a key osteoclastic transcription factor. TGF
      beta directly induces cytoplasmic NFATc1 expression within 24h, but is unable to
      stimulate NFATc1 nuclear translocation. Furthermore, RANKL-induced NFATc1
      expression is dependent on the presence of TGF-beta during the early stages of
      osteoclastogenesis. Similarly, TNF-alpha activates osteoclastogenesis by
      stimulating translocation of TGF-beta-induced NFATc1. In light of these findings,
      it is apparent that osteoclast formation is dependent on coordinated interactions
      between TGF-beta and RANKL/TNF-alpha that regulate the expression and
      intracellular distribution of NFATc1 during early stages of osteoclast
      differentiation.

PMID- 18060871
TI  - Effects of cathepsins B and L inhibition on postischemic protein alterations in
      the brain.
AB  - The effects of selective inhibition of cathepsins B and L on postischemic protein
      alterations in the brain were investigated in a rat model of middle cerebral
      artery occlusion (MCAO). Cathepsin B activity increased predominantly in the
      subcortical region of the ischemic hemisphere where the levels of collapsing
      mediator response protein 2, heat shock cognate 70 kDa protein, 60 kDa heat shock
      protein, protein disulfide isomerase A3 and albumin, were found to be
      significantly elevated. Postischemic treatment with Cbz-Phe-Ser(OBzl)-CHN(2),
      cysteine protease inhibitor 1 (CP-1), reduced infarct volume, neurological
      deficits and cathepsin B activity as well as the amount of heat shock proteins
      and albumin found in the brain. Our data strongly suggests that the decrease in
      heat shock protein levels and the significant reduction of serum albumin leakage
      into the brain following acute treatment with CP-1 is indicative of less
      secondary ischemic damage, which ultimately, is related to less cerebral tissue
      loss and improved neurological recovery of the animals.

PMID- 18060872
TI  - Betacellulin and nicotinamide sustain PDX1 expression and induce pancreatic beta
      cell differentiation in human embryonic stem cells.
AB  - The major obstacle in cell therapy of diabetes mellitus is the limited source of
      insulin-producing beta cells. Very recently, it was shown that a five-stage
      protocol recapitulating in vivo pancreatic organogenesis induced pancreatic beta
      cells in vitro; however, this protocol is specific to certain cell lines and
      shows much line-to-line variation in differentiation efficacy. Here, we modified
      the five-stage protocol for the human embryonic stem cell line SNUhES3 by the
      addition of betacellulin and nicotinamide. We reproduced in vivo pancreatic islet
      differentiation by directing the cells through stages that resembled in vivo
      pancreatic organogenesis. The addition of betacellulin and nicotinamide sustained
      PDX1 expression and induced beta-cell differentiation. C-peptide-a genuine marker
      of de novo insulin production-was identified in the differentiated cells,
      although the insulin mRNA content was very low. Further studies are necessary to
      develop more efficient and universal protocols for beta-cell differentiation.

PMID- 18060873
TI  - Analysis of bone marrow fatty acid composition using high-resolution proton NMR
      spectroscopy.
AB  - High-resolution 1H NMR spectroscopy as a complementary method in the analysis of
      human bone marrow fatty acid (FA) composition was examined. Marrow FA composition
      in 10 bone samples measured by NMR and gas chromatography (GC) were compared. NMR
      T1 relaxation time of FA was determined and reproducibility tests were performed
      to assess the variability. Good correlations were obtained between the NMR and GC
      results for omega-6 polyunsaturated fatty acid (PUFA) (Spearman r, 0.878), omega
      3 PUFA (0.895), monounsaturated FA (0.964) and saturated FA (0.939). The NMR
      method tended to overestimate saturated FA and underestimate omega-3/omega-6
      ratio compared to GC results. T1 relaxation time of marrow FA was 0.56-3.65s.
      Coefficient of variation of the NMR method was 0.6-8.2% in intra-experimental and
      0.2-8.4% in inter-experimental measurements. This study demonstrates a
      complementary role for 1H NMR spectroscopy as an additional analytical tool in
      human lipid research.

PMID- 18060874
TI  - The impact of membrane lipid composition on antimicrobial function of an alpha
      helical peptide.
AB  - VP1, a putative alpha-helical antimicrobial peptide (alpha-AMP) inhibited growth
      of Bacillus subtilis and Escherichia coli at 500microM. The peptide induced
      stable surface pressure changes in monolayers formed from B. subtilis native
      lipid extract (circa 4.5mNm(-1)) but transient pressure changes in corresponding
      E. coli monolayers (circa 1.0mNm(-1)), which led to monolayer disintegration.
      Synthetic lipid monolayers mimetic of the extracts were used to generate
      compression isotherms. Thermodynamic analysis of B. subtilis isotherms indicated
      membrane stabilisation by VP1 (DeltaG(Mix)<0), via a mechanism dependent upon the
      phosphatidylglycerol to cardiolipin ratio. Corresponding analysis of E. coli
      isotherms indicated membrane destabilisation by the peptide (DeltaG(Mix)>0).
      Destabilisation correlated with PE levels present and appeared to involve a
      mechanism resembling those used by tilted peptides. These data emphasise that
      structure/function analysis of alpha-AMPs must consider not only their structural
      characteristics but also the lipid make-up of the target microbial membrane.

PMID- 18060875
TI  - Characterization and structure elucidation of 12-hydroxyoctadec-cis-9-enoic acid
      in Jatropha gossypifolia and Hevea brasiliensis seed oils: a rich source of
      hydroxy fatty acid.
AB  - The seed oils containing hydroxy fatty acids are being used in various industries
      such as, in the production of nylon-11, in the manufacture of multi-purpose
      greases, as good anti-rust, new additives in water-soluble cutting fluids, and
      antimicrobial activity of various derivatives of ricinoleic acid polymers.
      Jatropha gossypifolia and Hevea brasiliensis seed oils were found to contain
      18.5% and 18.0% of 12-hydroxyoctadec-cis-9-enoic acid (ricinoleic acid),
      respectively. The identification and characterization was based on UV, FTIR, (1)H
      NMR, (13)C NMR, MS, GC analysis and chemical degradations.

PMID- 18060876
TI  - Crystallization and phase behavior of fatty acid esters of 1,3 propanediol III:
      1,3 propanediol dicaprylate/1,3 propanediol distearate (CC/SS) and 1,3
      propanediol dicaprylate/1,3 propanediol dipalmitate (CC/PP) binary systems.
AB  - The phase behavior of the 1,3 propanediol dicaprylate/1,3 propanediol distearate
      (CC/SS) and the 1,3 propanediol dicaprylate/1,3 propanediol dipalmitate (CC/PP)
      binary systems were investigated using different techniques. The two systems
      presented essentially the same overall features. XRD measurements detected CC-CC,
      PP-PP and SS-SS bilayers which crystallized in beta forms but no mixed bilayers
      for all mixtures. The phase diagrams of both systems were comparable and
      displayed a monotectic behavior. As strongly evidenced by XRD data, both phase
      diagrams suggested that CC, PP and SS formed largely separate phases but were
      probably not completely immiscible. Avrami analysis of SFC vs. time indicated
      heterogeneous nucleation and spherulitic crystal development from sporadic
      nuclei. However, noticeable differences in the manifestation of the molecular
      interactions have been detected at all levels of structure and confirmed by the
      interchange coupling determined by the enthalpy of melt, the final SFC and the
      hardness data. This was obviously related to the difference in chain size between
      SS and PP molecules. The effect on texture was highlighted by drastic
      microstructural differences between the two systems. Furthermore, the differences
      in nucleation and crystal growth, the more pronounced tendency for phase
      separation in the CC/SS system compared to the CC/PP system, and the relatively
      better crystallization of the CC/PP mixtures, particularly visibly for x(CC)< or
      =0.3 compared to the CC/SS mixtures were associated with the chain length
      difference.

PMID- 18060877
TI  - Thyroglobulin and human thyroid cancer.
AB  - Thyroglobulin (Tg) is a large molecule containing 2750 amino acids with a
      molecular weight of 330 kD and twenty putative N-linked glycosylation sites. Tg
      gene expression is regulated by thyroid transcription factor 1 (TTF-1) and human
      paired box 8 (Pax-8). Iodinated Tg is stored in the lumen of the thyroid
      follicles and is released in response to specific hormonal stimulation by thyroid
      stimulating hormone (TSH). Following Tg reabsorption by thyrocytes and subsequent
      degradation, thyroid hormones triiodothryronine (T(3)) and thyroxine (T(4)) are
      secreted in the bloodstream. Mutations within the Tg gene cause defective thyroid
      hormone synthesis, resulting in congenital hypothyroidism. Thyroid carcinoma may
      develop from dyshormonogenic goiters due to Tg mutation. Post-thyroidectomy Tg
      levels are apparently associated with prognosis of papillary and follicular
      thyroid carcinomas and may predict tumor recurrence and metastastic potential.
      The detection of Tg by biochemical and molecular means has important diagnostic
      significance due to its pleiotropic roles in identification of tissue of thyroid
      origin, differentiation, and post-operative follow-up.

PMID- 18060878
TI  - Pyruvate-sensitive AOX exists as a non-covalently associated dimer in the
      homeothermic spadix of the skunk cabbage, Symplocarpus renifolius.
AB  - The cyanide-resistant alternative oxidase (AOX) is a homodimeric protein whose
      activity can be regulated by the oxidation/reduction state and by alpha-keto
      acids. To further clarify the role of AOX in the skunk cabbage, Symplocarpus
      renifolius, we have performed expression and functional analyses of the encoding
      gene. Among the various tissues in the skunk cabbage, SrAOX transcripts were
      found to be specifically expressed in the thermogenic spadix. Moreover, our data
      demonstrate that the SrAOX protein exists as a non-covalently associated dimer in
      the thermogenic spadix, and is more sensitive to pyruvate than to other
      carboxylic acids. Our results suggest that the pyruvate-mediated modification of
      SrAOX activity plays a significant role in thermoregulation in the skunk cabbage.

PMID- 18060879
TI  - Crystal structure of RVV-X: an example of evolutionary gain of specificity by
      ADAM proteinases.
AB  - Russell's viper venom factor X activator (RVV-X) is a heterotrimeric
      metalloproteinase with a mammalian ADAM-like heavy chain and two lectin-like
      light chains. The crystal structure of RVV-X has been determined at 2.9 A
      resolution and shows a hook-spanner-wrench-like architecture, in which the
      metalloproteinase/disintegrin region constitutes a hook, and the lectin-like
      domains constitute a handle. A 6.5nm separation between the catalytic site and a
      putative exosite suggests a docking model for factor X. The structure provides a
      typical example of the molecular evolution of multi-subunit proteins and insights
      into the molecular basis of target recognition and proteolysis by
      ADAM/adamalysin/reprolysin proteinases.

PMID- 18060881
TI  - Peroxisome proliferation in Hansenula polymorpha requires Dnm1p which mediates
      fission but not de novo formation.
AB  - We show that the dynamin-like proteins Dnm1p and Vps1p are not required for re
      introduction of peroxisomes in Hansenula polymorpha pex3 cells upon
      complementation with PEX3-GFP. Instead, Dnm1p, but not Vps1p, plays a crucial
      role in organelle proliferation via fission. In H. polymorpha DNM1 deletion cells
      (dnm1) a single peroxisome is present that forms long extensions, which protrude
      into developing buds and divide during cytokinesis. Budding pex11.dnm1 double
      deletion cells lack these peroxisomal extensions, suggesting that the peroxisomal
      membrane protein Pex11p is required for their formation. Life cell imaging
      revealed that fluorescent Dnm1p-GFP spots fluctuate between peroxisomes and
      mitochondria. On the other hand Pex11p is present over the entire organelle
      surface, but concentrates during fission at the basis of the organelle extension
      in dnm1 cells. Our data indicate that peroxisome fission is the major pathway for
      peroxisome multiplication in H. polymorpha.

PMID- 18060880
TI  - S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves
      selective release of Smac/DIABLO and Omi/HtrA2.
AB  - A complex of two S100 EF-hand calcium-binding proteins S100A8/A9 induces
      apoptosis in various cells, especially tumor cells. Using several cell lines, we
      have shown that S100A8/A9-induced cell death is not mediated by the receptor for
      advanced glycation endproducts (RAGE), a receptor previously demonstrated to
      engage S100 proteins. Investigation of cell lines either deficient in, or over
      expressing components of the death signaling machinery provided insight into the
      S100A8/A9-mediated cell death pathway. Treatment of cells with S100A8/A9 caused a
      rapid decrease in the mitochondrial membrane potential (DeltaPsi(m)) and
      activated Bak, but did not cause release of apoptosis-inducing factor (AIF),
      endonuclease G (Endo G) or cytochrome c. However, both Smac/DIABLO and Omi/HtrA2
      were selectively released into the cytoplasm concomitantly with a decrease in
      Drp1 expression, which inhibits mitochondrial fission machinery. S100A8/A9
      treatment also resulted in decreased expression of the anti-apoptotic proteins
      Bcl2 and Bcl-X(L), whereas expression of the pro-apoptotic proteins Bax, Bad and
      BNIP3 was not altered. Over-expression of Bcl2 partially reversed the
      cytotoxicity of S100A8/A9. Together, these data indicate that S100A8/A9-induced
      cell death involves Bak, selective release of Smac/DIABLO and Omi/HtrA2 from
      mitochondria, and modulation of the balance between pro- and anti-apoptotic
      proteins.

PMID- 18060885
TI  - The generation gap at work: myth or reality?

PMID- 18060882
TI  - Regulation of CD20 expression by radiation-induced changes in intracellular redox
      status.
AB  - Increasing the levels of CD20 expression in cells that harbor low CD20 levels may
      enhance their responsiveness to CD20-specific antibody therapies. Here, we
      examined the regulation of CD20 expression after treatment with 0.5-2.0 Gy X
      irradiation and hydrogen peroxide (H(2)O(2)), in the presence or absence of known
      antioxidants, in the Burkitt lymphoma cell lines Daudi and Raji. Irradiation of
      cells enhanced cell-surface CD20 expression; the kinetics and extent of this
      change were cell-type specific and time-dependent. The kinetics of reactive
      oxygen species generation and changes in mitochondrial membrane potential after
      irradiation were also correlated with changes in CD20 expression. Raji and Daudi
      cells treated with H(2)O(2) showed a 2-to 2.5-fold increase in CD20 expression at
      12 and 20 h, respectively. Buthionine sulfoximine, which depletes glutathione,
      also increased surface CD20, whereas antioxidants, such as PEG-catalase, PEG-SOD,
      vitamin C, and amifostine, decreased CD20 expression induced by radiation or
      H(2)O(2). The antioxidant-mediated decrease in CD20 expression induced by
      radiation or H(2)O(2) suggests a mechanism involving redox regulation. These
      results demonstrate the critical role of radiation-induced oxidative stress in
      CD20 expression and may have implications for defining and improving the efficacy
      of CD20-targeted antibody therapy and radioimmunotherapy.

PMID- 18060886
TI  - Attracting and keeping volunteers in your organization.

PMID- 18060887
TI  - An update of trans-fat reduction in the American diet.

PMID- 18060888
TI  - Ethics Opinion: the RD and DTR are obligated to follow ethical standards when
      writing for the popular press.

PMID- 18060889
TI  - Truth in labeling: it's a matter of principle.

PMID- 18060890
TI  - From the gastronomic revolution to the new globesity epidemic.

PMID- 18060891
TI  - Birth size and accelerated growth during infancy are associated with increased
      odds of childhood overweight in Mexican children.
AB  - OBJECTIVE: The associations of birth size, rate of growth during infancy, and
      odds of childhood overweight have not yet been thoroughly investigated in
      contemporary cohorts in low- and middle-income countries. The primary aim of this
      study was to evaluate the influence of birth size (using body mass index at
      birth) and accelerated growth during infancy (defined as upward growth curve
      percentile crossing between birth and age 1 year) on the odds of childhood
      overweight. A secondary goal was to characterize the sociodemographic correlates
      of accelerated growth during infancy. DESIGN: Observational prospective cohort.
      SUBJECTS/SETTING: Participants were 163 children and their mothers living in
      semiurban Mexico who were originally recruited between 1997 and 2000 and followed
      until 2005. MAIN OUTCOME MEASURES: Primary outcome was childhood overweight (as
      assessed by body mass index). Secondary outcome was accelerated growth during
      infancy. STATISTICAL ANALYSES PERFORMED: Multivariate linear regression and
      logistic regression were used to determine the associations among birth size,
      accelerated growth, and childhood overweight. RESULTS: Increased size at birth
      and accelerated growth during the first year of life increased the odds of
      childhood overweight (odds ratio [OR] 7.62, P<0.0005 and OR 2.23, P<0.05,
      respectively). The effect of accelerated growth on odds of childhood overweight
      varied by size at birth (OR for interaction term 0.63, P<0.05). Living in a "dual
      burden" household, where the child was underweight at birth and the mother was
      overweight 4 to 6 years after birth, was associated with accelerated growth
      during the first year of life. CONCLUSIONS: In a sample of Mexican children
      living in poverty, accelerated growth during infancy was associated with
      increased odds of childhood overweight among small and normal-sized babies. Among
      large babies, accelerated growth did not appear to pose an additional risk for
      overweight beyond that of high birth weight. Upward growth curve percentile
      crossing in infancy may be predictive of future childhood overweight status,
      particularly among smaller infants.

PMID- 18060892
TI  - The rising cost of low-energy-density foods.
AB  - BACKGROUND: Consuming lower-energy-density foods is one recommended strategy for
      management of body weight. This cross-sectional study used retail food prices to
      test the hypothesis that low-energy-density foods are not only more costly per
      kilocalorie, but have increased disproportionately in price as compared to high
      energy-density foods. DESIGN: For a list of 372 foods and beverages belonging to
      a food frequency questionnaire database, retail prices were obtained from major
      supermarket chains in the Seattle, WA, metropolitan area in 2004 and 2006. Energy
      density of all items was calculated and prices were expressed as $/100 g edible
      portion and as $/1,000 kcal. Foods were stratified by quintiles of energy density
      and the differences in energy cost and in percent price change were tested using
      analyses of variance. RESULTS: High-energy-density foods provided the most
      dietary energy at least cost. Energy cost of foods in the bottom quintile of
      energy density, beverages excluded, was $18.16/1,000 kcal as compared to only
      $1.76/1,000 kcal for foods in the top quintile. The 2-year price change for the
      least energy-dense foods was +19.5%, whereas the price change for the most energy
      dense foods was -1.8%. CONCLUSION: The finding that energy-dense foods are not
      only the least expensive, but also most resistant to inflation, may help explain
      why the highest rates of obesity continue to be observed among groups of limited
      economic means. The sharp price increase for the low-energy-density foods
      suggests that economic factors may pose a barrier to the adoption of more
      healthful diets and so limit the impact of dietary guidance.

PMID- 18060893
TI  - Breastfeeding and health outcomes among citizen infants of immigrant mothers.
AB  - OBJECTIVE: To examine the associations between breastfeeding and child health
      outcomes among citizen infants of mothers immigrant to the United States.
      DESIGN/METHODS: From September 1998 through June 2004, as part of the Children's
      Sentinel Nutrition Assessment Program, a sentinel sample of 3,592 immigrant
      mothers with infants aged 0 to 12 months were interviewed in emergency
      departments or pediatric clinics in six sites. Mothers reported breastfeeding
      history, child health history, household demographics, government assistance
      program participation, and household food security. Infants' weight and length
      were recorded at the time of visit. Bivariate analyses identified confounders
      associated with breastfeeding and outcomes, which were controlled in logistic
      regression. Additional logistic regressions examined whether food insecurity
      modified the relationship between breastfeeding and child outcomes. RESULTS:
      Eighty-three percent of infants of immigrants initiated breastfeeding. Thirty-six
      percent of immigrant households reported household food insecurity. After
      controlling for potential confounding variables, breastfed infants of immigrant
      mothers were less likely to be reported in fair/poor health (adjusted odds ratio
      [AOR] 0.65, 95% confidence interval [CI] 0.50 to 0.85; P=0.001) and less likely
      to have a history of hospitalizations (AOR 0.72, CI 0.56 to 0.93, P=0.01),
      compared to nonbreastfed infants of immigrant mothers. Compared to nonbreastfed
      infants, the breastfed infants had significantly greater weight-for-age z scores
      (0.185 vs 0.024; P=0.006) and length-for-age z scores (0.144 vs -0.164;
      P<0.0001), but there was no significant difference in risk of overweight (weight
      for-age >95th percentile or weight-for-length >90th percentile) between the two
      groups (AOR 0.94, CI 0.73 to 1.21; P=0.63). Household food insecurity modified
      the association between breastfeeding and child health status, such that the
      associations between breastfeeding and child health were strongest among food
      insecure households. CONCLUSIONS: Breastfeeding is associated with improved
      health outcomes for infants of immigrant mothers. Breastfeeding is an optimal
      strategy in the first year of life to improve all infants' health and growth,
      especially for children of immigrants who are at greater risk for experiencing
      food insecurity.

PMID- 18060894
TI  - Poor nutrient intakes during 1-year follow-up with community-dwelling older
      adults with early-stage Alzheimer dementia compared to cognitively intact matched
      controls.
AB  - OBJECTIVE: Decreased food intakes, eating behavior disturbances, and loss of body
      weight are particularly significant problems among those with Alzheimer dementia.
      To follow the natural evolution of dietary and nutrition status among elderly
      community-dwelling adults with Alzheimer dementia. METHODS: With their
      caregivers, 36 community-dwelling patients in early stages of Alzheimer dementia,
      aged > or =65 years, were recruited from memory clinics in Montreal, age-matched
      to cognitively intact community-based controls (n=58), and interviewed at four to
      five time points (T0 to T4) across an 18-month period. Current diet and
      supplement use were assessed monthly by two food records and/or 24-hour diet
      recalls (666 records/recalls from patients and 1,678 records/recalls from
      controls), using adapted data collection techniques among patients, and analyzed
      using CANDAT with the 2001b Canadian Nutrient File. RESULTS: Nutrient intakes
      from diet and supplements were higher in control subjects, with significant
      differences in energy, the macronutrients, calcium, iron, zinc, vitamin K,
      vitamin A, and dietary fiber as well as n-3 and n-6 fatty acids. Repeated
      measures analysis of variance confirmed these observations among balanced groups
      of participants aged > or =70 years with full nutrient data during 12 months'
      follow-up. CONCLUSIONS: Dietary intakes by persons with Alzheimer dementia are
      poor compared to cognitively intact age-matched controls. Suboptimal diet is
      evident early in the onset of the disease. This vulnerable population would
      benefit from systematic dietary assessment and intervention to prevent further
      deterioration in food consumption and increased nutritional risk.

PMID- 18060895
TI  - Emergency preparedness needs assessment of centralized school foodservice and
      warehousing operations.
AB  - Managers of onsite retail foodservice operations, particularly those in
      centralized school foodservice operations, are called on to provide meals during
      emergencies, yet there is a paucity of research on their readiness to handle
      emergencies. Qualitative research and a cross-sectional survey design were used
      to conduct a needs assessment for emergency preparedness (emergency readiness,
      food recalls, and food defense) in centralized school foodservice operations,
      including warehousing. An open-ended written questionnaire was mailed to eight
      foodservice directors, and responses were used to develop a written questionnaire
      that was mailed to school foodservice directors in 200 districts identified as
      having centralized food production and warehousing. Directors from 78 districts
      responded (39% response rate). Most districts (n=72) had an emergency response
      team, and foodservice was included as part of 63 of those teams. Not all
      districts had written procedures for food recalls (47 of 73), natural disasters
      (37 of 74), or food defense (30 of 74). Barriers to implementing emergency
      preparedness policies and procedures included limited money, emergency equipment,
      and time. Most current training related to food safety with little training
      related to emergency preparedness. Training on the emergency preparedness plan
      was done in 61 of 78 districts. Training on emergency procedures was done by less
      than half of the districts during the previous year. This study identified best
      practices related to emergency preparedness that can be implemented in onsite
      retail foodservice operations. Results indicate a need to emphasize emergency
      preparedness, develop written standard operating procedures, and train employees
      to be prepared to respond to emergencies.

PMID- 18060896
TI  - Food composition data: the foundation of dietetic practice and research.
AB  - Food composition databases and dietary assessment systems are important tools for
      food and nutrition professionals. The availability and accessibility of data have
      improved over time along with the technology to convert the information into
      useful formats for planning diets, writing educational materials, counseling
      patients, and conducting research. Primary sources of food composition data
      include government, academic, and other institutional databases; the food
      industry; and scientific literature. Changes in the marketplace affect food
      availability and composition and affect the accuracy and adequacy of food
      composition databases. Improvements in both food composition data and in dietary
      assessment methods have worked synergistically to improve estimates of dietary
      intake. The development of databases for food frequency assessment systems
      requires special considerations for data aggregation for each food or food
      grouping in the questionnaires. Considerations for selecting a dietary assessment
      system include appropriateness of the data for the intended audience or purpose,
      efficiency of the search strategy for retrieving data, content and format of
      summary information, and cost. Needs for food composition data vary depending on
      dietetic practice area; however, most food and nutrition professionals will
      benefit from becoming more informed about food composition data, exploring new
      ways to educate themselves about databases and database systems, and advocating
      for what is most needed in dietetic practice.

PMID- 18060898
TI  - Brief psychosocial fruit and vegetable tool is sensitive for the US Department of
      Agriculture's Nutrition Education Programs.
AB  - The usefulness of an evaluation instrument is dependent on its reliability,
      validity, and ability to capture change. The latter psychometric characteristic
      is particularly important, yet is often neglected. The purpose of this study was
      to assess the sensitivity of a psychosocial fruit and vegetable evaluation tool
      for use by two US Department of Agriculture community-based programs. As part of
      a prospective randomized controlled trial, a sample of limited-resource women
      (n=93), recruited from eight counties, provided dietary recalls, behavioral
      assessments, and psychosocial assessments. A randomly selected subsample was used
      for venipuncture (n=55). Sensitivity of the tool was estimated using serum
      carotenoids, selected micronutrients, fruit/vegetable servings, and
      fruit/vegetable behaviors. Controlling for energy intake at baseline and change
      in energy intake, the change scores for the tool were correlated with reported
      changes in fruit and vegetable behaviors (r=0.28, P=0.01), vitamin C (r=0.25,
      P=0.02), and the biomarker serum carotenoids (r=0.31, P=0.02). This systematic
      process yielded a moderately sensitive evaluation tool useful with a limited
      resource audience participating in two US Department of Agriculture programs.
      This is the first study to estimate sensitivity of a psychosocial tool for a
      fruit and vegetable intervention.

PMID- 18060897
TI  - Nutrient status of adults with cystic fibrosis.
AB  - Nutrition is thought to influence disease status in patients with cystic fibrosis
      (CF). This cross-sectional study sought to evaluate nutrient intake and
      anthropometric data from 64 adult outpatients with cystic fibrosis. Nutrient
      intake from food and supplements was compared with the Dietary Reference Intakes
      for 16 nutrients and outcomes influenced by nutritional status. Attention was
      given to vitamin D and calcium given potential skeletal implications due to
      cystic fibrosis. Measurements included weight, height, body composition,
      pulmonary function, and serum metabolic parameters. Participants were interviewed
      about dietary intake, supplement use, pulmonary function, sunlight exposure, and
      pain. The participants' mean body mass index (+/-standard deviation) was 21.8+/
      4.9 and pulmonary function tests were normal. Seventy-eight percent used
      pancreatic enzyme replacement for malabsorption. Vitamin D deficiency [25
      hydroxyvitamin D (25OHD)<37.5 nmol/L] was common: 25 (39%) were deficient despite
      adequate vitamin D intake. Lipid profiles were normal in the majority, even
      though total and saturated fat consumption represented 33.0% and 16.8% of energy
      intake, respectively. Reported protein intake represented 16.9% of total energy
      intake (range 10%-25%). For several nutrients, including vitamin D and calcium,
      intake from food and supplements in many participants exceeded recommended
      Tolerable Upper Intake Levels. Among adults with cystic fibrosis, vitamin D
      deficiency was common despite reported adequate intake, and lipid profiles were
      normal despite a relatively high fat intake. Mean protein consumption was
      adequate, but the range of intake was concerning, as both inadequate or excessive
      intake may have deleterious skeletal effects. These findings call into question
      the applicability of established nutrient thresholds for patients with cystic
      fibrosis.

PMID- 18060899
TI  - Long-haul truck drivers want healthful meal options at truck-stop restaurants.
AB  - Long-haul truckers are confined, by parking regulations and other constraints, to
      dining at truck-stop restaurants. Objectives were to (a) compare truckers'
      anthropometrics with recommended guidelines; and (b) assess eating/exercise
      habits, importance of healthful food choices, and attitudes about restaurants'
      provision of healthful options. Hypotheses were: (a) overweight/obese drivers
      will place less importance on healthful food choices than will drivers of optimal
      weight; (b) importance of healthful food choices and attitudes about their
      provision will be positively correlated. Questionnaires included Food Choices
      Index, Nutrition Attitude Survey, and demographic information; bioelectrical
      impedance assessed weight, body fat, and body mass index. Subjects (n=92) were
      truckers at a Midwestern truck-stop restaurant; 79 were overweight, 52 were
      obese. Mean rating of importance of healthful choices was above average. There
      was no difference in importance of healthful food choices for overweight/obese
      and optimal weight drivers, t(89)=-1.312; P=0.19. Drivers placing more importance
      on healthful food choices had more positive attitudes about restaurants'
      provision of such options, r(90)=0.74, P<0.001. Overall, drivers indicated they
      would choose healthful foods if available and appetizing. Registered dietitian
      directed wellness programs that include education, support, and cooperation of
      truck-stop restaurants are critical to reduce obesity and risk of disease in this
      population.

PMID- 18060900
TI  - Knowledge, attitudes, and label use among college students.
AB  - This study examined the relationships among nutrition education, knowledge,
      attitude, use of nutritional supplements, and label reading behavior among 537
      randomly selected college students using a conceptual model. The majority of the
      respondents were women, undergraduate students, and nonsmokers. The mean age was
      23+/-6.1 years. A higher percentage of undergraduate students and women had prior
      exposure to nutrition education, a positive attitude, and greater knowledge of
      food labels as compared to their graduate and male peers. The structural equation
      model indicated nutrition education, age, sex, and attitude predicted label use;
      prior nutrition education and a positive attitude exhibited the strongest
      (direct) effects on label reading behavior. Attitude mediated the relationship
      between knowledge and label reading behavior. The indexes of fit for the tested
      model indicated a good fit; the predictors accounted for 44% of the variance in
      label usage.

PMID- 18060901
TI  - Noninfective endocarditis in rheumatoid arthritis.

PMID- 18060902
TI  - Individualized treatment of foramen ovale and stroke.

PMID- 18060903
TI  - Patent foramen ovale and cryptogenic stroke.

PMID- 18060905
TI  - Exercise, vitamins and respiratory tract infections.

PMID- 18060907
TI  - Anti-TNF antibodies associated with different risk of latent tuberculosis
      activation.

PMID- 18060909
TI  - Currently used medicines for Alzheimer's disease are not very effective.

PMID- 18060911
TI  - Clinical perspectives of statin-induced rhabdomyolysis.

PMID- 18060912
TI  - Potential ipriflavone and warfarin interaction.

PMID- 18060913
TI  - Testing for stain-induced myopathy.

PMID- 18060915
TI  - Pneumococcal pyomyositis in a patient infected with human immunodeficiency virus.

PMID- 18060916
TI  - Incidental administration of corticosteroid can mask the diagnosis of
      tuberculosis.

PMID- 18060917
TI  - Travel bugs.

PMID- 18060918
TI  - Sepsis.
AB  - Sepsis is a clinical syndrome defined by a systemic response to infection. With
      progression to sepsis-associated organ failure (ie, severe sepsis) or hypotension
      (ie, septic shock) mortality increases. Sepsis is a cause of considerable
      mortality, morbidity, cost, and health care utilization. Abnormalities in the
      inflammation, immune, coagulation, oxygen delivery, and utilization pathways play
      a role in organ dysfunction and death. Early identification of septic patients
      allows for evidence-based interventions, such as prompt antibiotics, goal
      directed resuscitation, and activated protein C. Appropriate care for sepsis may
      be more easily delivered by dividing this clinical entity into various stages and
      with changes in structures of delivery that extend across traditional boundaries.
      Better description of the molecular basis of the disease process also will allow
      for more targeted therapies.

PMID- 18060919
TI  - Hard to swallow.

PMID- 18060920
TI  - A prickly pair.

PMID- 18060921
TI  - Spotting a zebra by its stripes.

PMID- 18060922
TI  - A cut above.

PMID- 18060923
TI  - Viral elimination reduces incidence of malignant lymphoma in patients with
      hepatitis C.
AB  - PURPOSE: A high prevalence of malignant lymphoma among patients with hepatitis C
      virus (HCV) infection has been reported. The aim of this retrospective study was
      to determine the incidence of malignant lymphoma and the relationship between
      malignant lymphoma and viral elimination in patients with HCV. METHOD: We studied
      501 consecutive HCV-infected patients who had never received interferon therapy
      and 2708 consecutive HCV-infected patients who received interferon therapy.
      RESULTS: In the non-interferon group, the cumulative rates of malignant lymphoma
      development were 0.6% at the 5th year, 2.3% at the 10th year, and 2.6% at the
      15th year. The cumulative rates of malignant lymphoma development in interferon
      treated patients with sustained virologic response were 0% at the 5th year, 0% at
      the 10th year, and 0% at the 15th year. The cumulative rates of malignant
      lymphoma development with persistent infection were 0.4% at the 5th year, 1.5% at
      the 10th year, and 2.6% at the 15th year. The malignant lymphoma development rate
      was higher in patients with persistent infection than in patients with sustained
      virologic response (P=.0159). The hazard ratio of lymphomagenesis in 1048
      patients with sustained virologic response was significantly lower than in
      patients with persistent infection (hazard ratio: 0.13; P=.049). CONCLUSION: Our
      retrospective study is the first to determine the annual incidence of malignant
      lymphoma among patients with HCV at 0.23%. Our results indicate that sustained
      virologic response induced by interferon therapy protects against the development
      of malignant lymphoma in patients with chronic HCV.

PMID- 18060924
TI  - Skin temperature monitoring reduces the risk for diabetic foot ulceration in high
      risk patients.
AB  - PURPOSE: To evaluate the effectiveness of home temperature monitoring to reduce
      the incidence of foot ulcers in high-risk patients with diabetes. METHODS: In
      this physician-blinded, 18-month randomized controlled trial, 225 subjects with
      diabetes at high risk for ulceration were assigned to standard therapy (Standard
      Therapy Group) or dermal thermometry (Dermal Thermometry Group) groups. Both
      groups received therapeutic footwear, diabetic foot education, regular foot care,
      and performed a structured foot inspection daily. Dermal Thermometry Group
      subjects used an infrared skin thermometer to measure temperatures on 6 foot
      sites twice daily. Temperature differences >4 degrees F between left and right
      corresponding sites triggered patients to contact the study nurse and reduce
      activity until temperatures normalized. RESULTS: A total of 8.4% (n=19) subjects
      ulcerated over the study period. Subjects were one third as likely to ulcerate in
      the Dermal Thermometry Group compared with the Standard Therapy Group (12.2% vs
      4.7%, odds ratio 3.0, 95% confidence interval, 1.0 to 8.5, P=.038). Proportional
      hazards regression analysis suggested that thermometry intervention was
      associated with a significantly longer time to ulceration (P=.04), adjusted for
      elevated foot ulcer classification (International Working Group Risk Factor 3),
      age, and minority status. Patients that ulcerated had a temperature difference
      that was 4.8 times greater at the site of ulceration in the week before
      ulceration than did a random 7 consecutive-day sample of 50 other subjects that
      did not ulcerate (3.50+/-1.0 vs 0.74+/-0.05, P=.001). CONCLUSIONS: High
      temperature gradients between feet may predict the onset of neuropathic
      ulceration and self-monitoring may reduce the risk of ulceration.

PMID- 18060925
TI  - Hospital discharge against advice after myocardial infarction: deaths and
      readmissions.
AB  - BACKGROUND: Approximately 1% of patients leave hospitals against medical advice,
      but the clinical significance of premature hospital discharge is unknown,
      particularly after admission for acute myocardial infarction (AMI). METHODS: We
      used California hospital discharge data (1998-2000) to compare readmissions and
      mortality among patients admitted for AMI who were discharged against medical
      advice with those who weren't. Effects were adjusted for age, race, income,
      comorbidity, insurance, and hospital characteristics. We also examined whether
      the effects of premature hospital discharge were partly explained by lower rates
      of coronary revascularization. RESULTS: There were 1079 patients (1.1% of the
      sample) with AMI on admission who left against medical advice. Compared with
      those who didn't leave against medical advice, these patients were younger, more
      often male, low income, black, insured through Medicaid or uninsured, and had
      less physical comorbidity, but greater mental health comorbidity. Their mean
      length of stay was shorter (4 vs 8 days) than those who stayed. They were
      transferred less often. They received fewer cardiac procedures, including
      coronary revascularization. In multivariate analyses, they had 60% higher risk
      for death or re-admission for AMI or unstable angina up to 2 years postdischarge
      than patients with standard discharge (hazard ratio 1.59; 95% confidence
      interval, 1.43-1.77). Adjustment for revascularization attenuated, but did not
      eliminate, this risk (hazard ratio 1.39; 95% confidence interval, 1.25-1.55).
      CONCLUSIONS: Discharge against medical advice after AMI is associated with
      appreciable morbidity and mortality. These results should be used to manage AMI
      patients contemplating such discharge.

PMID- 18060926
TI  - C-reactive protein, inflammatory conditions, and cardiovascular disease risk.
AB  - BACKGROUND: It is uncertain to what extent high C-reactive protein (CRP)
      concentrations reflect the presence of inflammatory conditions in the community.
      METHODS: We evaluated 3782 Framingham Offspring Study participants (mean age 55
      years; 52% women) free of baseline cardiovascular disease. Logistic regression
      models examined the prevalence of common inflammatory conditions by CRP
      categories, while a separate matched case-referent analysis evaluated the
      prevalence of uncommon inflammatory conditions. Cox models were used to assess
      the influence of common inflammatory conditions on relations between CRP and
      incident cardiovascular disease. RESULTS: Common inflammatory conditions were
      reported by nearly half of the participants; these individuals were more likely
      to have markedly high CRP concentrations (>10 mg/L, P for trend=.001). In
      multivariable models, there were increased odds of having at least one common
      inflammatory condition with CRP concentrations of 1-3.0, 3.01-10, and >10 mg/L,
      compared with the referent category (<1 mg/L); the respective odds ratios with
      95% confidence intervals were 1.41 (1.07-1.86), 1.45 (1.07-1.98), and 1.64 (1.09
      2.47) in men, and 1.08 (0.82-1.43), 1.07 (0.80-1.44), and 1.38 (0.97-1.96) in
      women. In case-referent analyses, uncommon inflammatory conditions were more
      common in individuals with CRP >10 mg/L compared with those with CRP <1 mg/L
      (12.1% vs 6.6%; P=.0001). In multivariable models, higher CRP categories were not
      associated with incident cardiovascular disease, and with additional adjustment
      for inflammatory conditions, results remained unchanged. CONCLUSION: There is
      high prevalence of common and uncommon inflammatory conditions in individuals
      with high CRP concentrations. Higher CRP concentrations should be interpreted
      with caution in cardiovascular disease risk assessment.

PMID- 18060927
TI  - Outcomes in patients with chronic kidney disease referred late to nephrologists:
      a meta-analysis.
AB  - PURPOSE: The study purpose was to compare differences in mortality and the
      duration of hospitalization in patients with chronic kidney disease who are
      referred early versus late to nephrologists. METHODS: We searched English
      language literature from 1980 through December 2005, along with national
      conference proceedings, the Web of Science Citation Index, and reference lists of
      all included studies. Twenty-two studies with a total sample size of 12,749 met
      inclusion criteria. RESULTS: There was significantly increased overall mortality
      in the late referral group as compared with the early referral group (relative
      risk 1.99; 95% confidence interval [CI], 1.66 to 2.39, P <.0001). The duration of
      hospital stay, at the time of initiation of renal replacement therapy, was
      greater in the late referred group by an average of 12 days (95% CI, 8.0 to 16.1,
      P=.0007). Significant heterogeneity was detected for both outcomes. CONCLUSION:
      Timing of referral emerged to be a significant factor impacting homogeneity in
      the mortality outcome. Our results suggest significantly higher mortality and
      increased early hospitalization of chronic kidney disease subjects referred late
      to nephrologists as compared with earlier referred subjects.

PMID- 18060928
TI  - The characteristics and prognostic importance of NT-ProBNP concentrations in
      critically ill patients.
AB  - BACKGROUND: There are limited data for prognostic and diagnostic use of
      natriuretic peptides in intensive care unit (ICU) patients. We evaluate amino
      terminal brain natriuretic peptide (NT-proBNP) in the medical ICU, specifically
      its correlation with noncardiac admission diagnosis and prognosis of critically
      ill patients. METHODS: NT-proBNP (pg/mL) was measured in 179 ICU patients without
      acute decompensated heart failure or acute coronary syndrome. Death during
      hospitalization (mortality), APACHE II score, laboratory data, echocardiograms,
      medical history, and demographics were assessed. NT-proBNP concentrations were
      compared with established cutoffs for congestive heart failure (>450 pg/mL for
      patients <50 years of age, >900 pg/mL for patients 50-70 years of age, and >1800
      pg/mL for patients >70 years of age). Predictors of mortality and of NT-proBNP
      were analyzed by regression analysis. Tertiles were compared by analysis of
      variance and chi-squared test. RESULTS: NT-proBNP was elevated in these ICU
      patients (median 2139 pg/mL, 25th percentile 540 pg/mL, 75% percentile 7389
      pg/mL). Severity of illness and renal dysfunction (APACHE II score and serum
      creatinine) increased with rising NT-proBNP. The incidence of acute respiratory
      distress syndrome, sepsis, death, history of coronary artery disease (CAD) or
      congestive heart failure (all P <.05) increased with each tertile. Independent
      predictors of increased NT-proBNP were creatinine (P <.001), CAD (P <.001),
      APACHE II score (P <.05), and sepsis (P < or =.001). Overall hospital mortality
      was 26%, and log NT-proBNP (P <.05), APACHE II (P < or =.001), and CAD (P <.05)
      were independent predictors of mortality. CONCLUSIONS: For patients admitted to
      the ICU without decompensated heart failure or acute coronary syndrome, NT-proBNP
      concentrations are markedly elevated, especially in patients with sepsis. NT
      proBNP strongly and independently predicts mortality. However, NT-proBNP should
      not be used to direct volume management in critically ill patients.

PMID- 18060929
TI  - Bloodstream infections in a geriatric cohort: a population-based study.
AB  - PURPOSE: Health care-associated infections are those that do not meet the
      definition of nosocomial but are acquired by patients with extensive exposure to
      the health care system placing them at higher risk for resistant organisms. This
      category is particularly common among elderly patients. The objective of this
      study was to describe and compare the epidemiologic characteristics of community
      acquired, health care-associated and nosocomial bloodstream infections in a
      geriatric population. METHODS: A population-based, retrospective study of all
      patients aged 65 years or greater with positive blood cultures (n=636) identified
      between January 1, 2003 and December 31, 2005 in Olmsted County, Minnesota.
      Exposures and clinical information were ascertained through complete chart
      review, utilizing the resources of the Rochester Epidemiology Project. A total of
      347 incident patients with bloodstream infection were identified. Bloodstream
      infections were described as community-acquired, health care-associated or
      nosocomial using standardized definitions. Variables analyzed included source,
      isolate, risk factors, and mortality. RESULTS: The distribution of bloodstream
      infection cases that were community-acquired, health care-associated, and
      nosocomial was 159 (46%), 151 (44%), and 37 (10%), respectively. The prevalence
      of methicillin-resistant Staphylococcus aureus among S. aureus isolates was 54%
      and 44% for health care-associated and nosocomial cases, respectively. Fourteen
      day mortality among bloodstream infection cases was the same in health care
      associated and nosocomial infections (15% vs 14%), and was less in community
      acquired (6%) cases (P=.04). CONCLUSIONS: The category of health care-associated
      infection identified a unique group of geriatric patients at increased risk of
      methicillin-resistant Staphylococcus aureus infection and with increased
      mortality.

PMID- 18060930
TI  - Oxidative stress and severe walking disability among older women.
AB  - BACKGROUND: Oxidative stress has been implicated in sarcopenia and the loss of
      muscle strength with aging, but the relationship between oxidative stress and
      decrease in muscle strength and physical performance has not been well
      characterized. Serum protein carbonyls are markers of oxidative damage to
      proteins and are caused by oxidative stress. METHODS: Serum protein carbonyls
      were measured at baseline and compared with a decrease in walking speed and
      development of severe walking disability (inability to walk or walking speed <0.4
      m/sec) over 36 months of follow-up in 545 moderately to severely disabled women,
      aged > or =65 years, living in the community in Baltimore, Maryland (the Women's
      Health and Aging Study I). RESULTS: After adjusting for age, body mass index,
      smoking, and chronic diseases, log(e) protein carbonyls (nmol/mg) were associated
      with a decrease in walking speed over 36 months (P=.002). During follow-up, 154
      women (28.2%) developed severe walking disability. After adjusting for the same
      potential confounders, log(e) protein carbonyls were associated with incident
      severe walking disability (hazards ratio 1.42, 95% confidence interval, 1.02
      1.98, P=.037). CONCLUSION: High oxidative stress, as indicated by oxidative
      damage to proteins, is an independent predictor of decrease in walking speed and
      progression to severe walking disability among older women living in the
      community.

PMID- 18060931
TI  - Combining neuroendocrine inhibitors in heart failure: reflections on safety and
      efficacy.
AB  - Neuroendocrine activation in heart failure has become the major target of
      pharmacotherapy for this growing epidemic. Agents targeting the renin-angiotensin
      aldosterone and sympathetic nervous systems have shown cardiovascular and
      survival benefits in clinical trials. Beta-blockers and angiotensin-converting
      enzyme (ACE) inhibitors remain the mainstream initial therapy. The benefits of
      aldosterone antagonists have been demonstrated in advanced heart failure
      (spironolactone) and after myocardial infarction complicated by left ventricular
      dysfunction and heart failure (eplerenone). Emerging clinical evidence
      demonstrated that angiotensin receptor blockers may be a reasonable alternative
      to ACE inhibitors in patients with heart failure (candesartan) and following
      myocardial infarction complicated by heart failure or left ventricular
      dysfunction (valsartan). Angiotensin receptor blockers (candesartan) also
      provided incremental benefits when added to ACE inhibitors in chronic heart
      failure. Thus, combining neuroendocrine inhibitors in heart failure appears both
      biologically plausible and evidence-based. However, this approach raised concerns
      about side effects, such as hypotension, renal insufficiency, hyperkalemia, and
      others. Close follow-up and implementation of evidence-based medicine (ie, using
      agents and doses proven beneficial in clinical trials) should therefore be
      undertaken when combining neuroendocrine inhibitors.

PMID- 18060932
TI  - Predicting, preparing for, and creating the future: what will happen to internal
      medicine?

PMID- 18060933
TI  - Cicero and healthy aging.

PMID- 18060935
TI  - Pregnancy-associated spontaneous coronary artery dissection.
AB  - Spontaneous coronary artery dissection is a rare cause of acute myocardial
      infarction that occurs particularly in women during the pregnancy and in the
      postpartum period. We describe a dramatic case of pregnancy-related spontaneous
      left main coronary artery dissection that resulted in acute myocardial infarction
      with severe left ventricular dysfunction and was complicated by acute heart
      failure and cardiogenic shock. Urgent revascularization and restoration of
      myocardial perfusion that were performed in this case resulted in marked left
      ventricular function recovery and clinical improvement.

PMID- 18060936
TI  - Stage IIB carcinoma of the cervix that is associated with pelvic kidney: A
      therapeutic dilemma.
AB  - Locally advanced cervical cancer with congenital pelvic kidney is reported
      uncommonly. A 50-year-old patient with stage IIB cervical cancer and pelvic
      kidney was treated with irradiation and concurrent chemotherapy. Follow-up
      evaluation for 2 years revealed normal renal function and no evidence of
      recurrent disease.

PMID- 18060937
TI  - Combination therapy for treatment of osteoporosis: A review.
AB  - Combination therapy for osteoporosis has been tested in small trials of short
      duration with various combinations. Pertinent human and animal randomized
      clinical trial data were identified through Medline and reviewed with a focus on
      the risks and benefits of different types of combination therapies. Improvements
      in bone density were found in some, but not all, combinations. There are no large
      trials of adequate length or numbers to determine fracture efficacy. Consider
      combination therapy if monotherapy is unsuccessful, if there is an added
      nonskeletal benefit to the proposed combination or as sequential treatment with
      an anabolic agent followed by an antiresorptive agent. Although combination
      therapy, in general, has limitations based on cost, concern about potential
      oversuppression of bone, and lack of long-term safety and fracture efficacy,
      selected patients may benefit.

PMID- 18060938
TI  - Reducing the burden of glandular carcinomas of the uterine cervix.
AB  - Widespread use of the Papanicolaou test for the screening of cervical cancers has
      lead to a significant decline in overall incidence and mortality rates over the
      past 3 decades. When different histologic types of cervical cancers are
      considered and trends are reexamined, it becomes apparent that observed declines
      are reflective of squamous cell carcinomas predominantly; the rates for
      adenocarcinomas continue to rise. This rise in incidence may be due to the
      greater difficulty in screening for glandular precursor lesions that often arise
      high within the endocervical canal. Reducing the incidence and mortality rates
      that are associated with adenocarcinomas can be accomplished by using improved
      screening techniques and large-scale implementation of cervical cancer vaccines
      that target the predominant oncogenic human papillomavirus types that are
      associated with adenocarcinoma.

PMID- 18060939
TI  - The identification, management, and prevention of conflict with faculty and
      fellows: A practical ethical guide for department chairs and division chiefs.
AB  - The relationship between chairs and divisions chiefs with faculty colleagues in
      departments of obstetrics and gynecology has important but heretofore unexplored
      ethical dimensions. Based on the ethical concept of fiduciary responsibility and
      contractual obligations, this paper provides ethically justified practical
      guidance for academic physician leaders in the identification, management, and
      prevention of conflicts in their relationships with faculty colleagues. The
      framework is developed in contrast with the fiduciary-contractual dimensions of
      the physician-patient relationship and is articulated in terms of the ethical
      principles of beneficence, respect for autonomy, and justice. The distinctive
      nature of the academic physician leader-colleague relationship is that
      beneficence-based obligations and justice-based obligations to colleagues can
      often justifiably override autonomy-based obligations to colleagues, about which
      it is crucial for academic leaders to be transparent in making and implementing
      leadership decisions.

PMID- 18060940
TI  - A pilot study to evaluate the relative efficacy of endometrial biopsy and full
      curettage in making a diagnosis of endometriosis by the detection of endometrial
      nerve fibers.
AB  - OBJECTIVE: The purpose of this study was to evaluate endometrial biopsy and
      curettage in detecting small nerve fibers in eutopic endometrium for diagnosis of
      endometriosis. STUDY DESIGN: Endometrial biopsies with precise, consistent
      technique and curettings were taken from 37 women (20 with endometriosis and 17
      without endometriosis). Sensitivity, specificity, and positive and negative
      predictive value were formally calculated. Endometrial nerve fibers were
      immunohistochemically detected using the pan-neuronal marker PGP9.5. RESULTS:
      Small nerve fibers were detected in all endometrial biopsies and curettings from
      all 20 women with endometriosis, but were not detected in endometrium taken from
      17 women without endometriosis. Mean (+/-SD) nerve fiber density in the
      endometrial biopsies was 26.8 per mm(2) +/- 55.9 (range, 1.6-125) and for
      curettings was 21.6 per mm(2) +/- 33.1 (range, 0.8-250), with 100% specificity,
      sensitivity, and positive and negative predictive value. CONCLUSION: Careful
      endometrial biopsy combined with immunohistochemical staining for nerve fibers
      may be a reliable means of diagnosing or excluding endometriosis.

PMID- 18060941
TI  - Second-trimester loss and subsequent pregnancy outcomes: What is the real risk?
AB  - OBJECTIVE: This study was performed to determine whether second-trimester
      pregnancy loss was associated with an increased risk for spontaneous preterm
      birth or recurrent second-trimester loss in a subsequent pregnancy. STUDY DESIGN:
      A retrospective cohort study was conducted. Patients with a second-trimester
      pregnancy loss (n = 38), a spontaneous preterm birth (n = 76), and a full term
      delivery (n = 76) were identified from 2002 to 2005 (index pregnancy).
      Computerized medical records were used to obtain demographic and obstetrical
      histories. RESULTS: Frequencies of subsequent second-trimester loss were 27%, 3%,
      and 1% in the second-trimester loss, spontaneous preterm birth, and full-term
      delivery cohorts, respectively. Frequencies of subsequent spontaneous preterm
      birth were 33%, 39.5%, and 9% in the same 3 cohorts. Patients with a prior second
      trimester loss were 10.8 times more likely to have recurrent second-trimester
      loss or spontaneous preterm birth, compared with those with prior full-term
      delivery (confidence interval 3.6 to 32.1, P < .0001). CONCLUSION: Patients with
      a prior second-trimester loss are at significantly increased risk for spontaneous
      preterm birth and recurrent second-trimester loss in their next pregnancy.

PMID- 18060942
TI  - The effect of intrapartum penicillin on vaginal group B streptococcus colony
      counts.
AB  - OBJECTIVE: The objective of the study was to determine the temporal relationship
      between intrapartum penicillin-G (PCN-G) and vaginal group B streptococcus (GBS)
      counts. STUDY DESIGN: In 50 women with GBS-positive antenatal cultures,
      intrapartum cultures were collected just before the first PCN-G dose and every 2
      hours x 4 or until delivery. Colony counts were quantified using serial dilution.
      Results were standardized as percent of initial colony count and analyzed using
      sequential Wilcoxon tests. RESULTS: Of 50 subjects with GBS-positive antepartum
      cultures, 35 (70%) had positive intrapartum vaginal cultures, of which 27
      received intrapartum PCN-G. Degree of vaginal colonization varied greatly between
      subjects, and counts (percents) were not normally distributed. From the T(0)
      (time = zero) colony count standardized to 100%, counts fell rapidly to means +/-
      SE and medians of 18.2 +/- -7.5% and 0.5% at T(2) (P < .0001), 2.5 +/- 1.7% and
      0.02% at T(4) (P = .006), and less than 0.2% and 0.0% at T(6 and 8) (P = .07 and
      P = .46, respectively). CONCLUSION: Vaginal GBS colony counts fall rapidly after
      intrapartum PCN-G administration, which may partly explain the effectiveness of
      chemoprophylaxis.

PMID- 18060943
TI  - Maternal corticosteroid use and orofacial clefts.
AB  - OBJECTIVE: The purpose of this study was to examine whether maternal
      corticosteroid use during pregnancy is associated with delivering an infant with
      an orofacial cleft. STUDY DESIGN: This study included data on deliveries from the
      National Birth Defects Prevention Study, which is a population-based case-control
      study. Exposures were assessed by telephone interviews for mothers of 1141 cases
      with cleft lip +/- cleft palate (CLP), 628 with cleft palate (CP), and 4143
      controls. RESULTS: Mothers of 33 infants with CLP (2.9%), mothers of 6 infants
      with CP (1.0%), and 72 control subjects (1.7%) reported corticosteroid use from 4
      weeks before through 12 weeks after conception. The crude odds ratio for "any" vs
      "no" use was 1.7 (95% CI, 1.1-2.6) for CLP and 0.5 (0.2-1.3) for CP. When
      analyzed by route of administration and medication components, odds ratios for
      CLP tended to be elevated, and odds ratios for CP tended to be close to 1.
      CONCLUSION: Our results suggest a moderately increased risk of CLP among women
      who use corticosteroids during early pregnancy.

PMID- 18060944
TI  - Placental sharing, birthweight discordance, and vascular anastomoses in
      monochorionic diamniotic twin placentas.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      placental territory and birthweight discordance and vascular anastomoses in
      monochorionic diamniotic twin placentas from pregnancies that were not
      complicated by twin-to-twin transfusion syndrome with 2 liveborn twins. STUDY
      DESIGN: Placentas originated from a prospective follow-up study of monochorionic
      diamniotic twins included in the first trimester. After injection with dyed
      barium sulphate, a digital x-ray angiography and high-resolution digital
      photograph were taken. The 2 venous territories were delineated on the angiogram.
      The diameter of each arterioarterial anastomosis and of each vein that
      participated in an arteriovenous anastomosis was measured on the digital
      photograph. Net transfusion over the arteriovenous anastomoses was calculated as
      the difference between the total venous diameters of the 2 placental parts.
      RESULTS: One hundred placentas were analyzed. Birthweight discordance increased
      with placental territory discordance (P < .0001). Arterioarterial diameter (P <
      .01), net arteriovenous transfusion (P < .001), and total anastomotic diameter (P
      < .01) increased with placental territory discordance. On the other hand,
      birthweight discordance for a given placental territory discordance decreased
      with increasing arterioarterial diameter (P < .01), net arteriovenous transfusion
      (P < .001), and total anastomotic diameter (P < .01). CONCLUSION: In unequally
      shared placentas, the 2 fetal circulations are more tightly linked than in
      equally shared placentas, which may reduce the birthweight discordance for a
      given placental territory discordance.

PMID- 18060945
TI  - Relationship between follicle number and (multiple) live birth rate after
      controlled ovarian hyperstimulation and intrauterine insemination.
AB  - OBJECTIVES: The goal of this study was to determine the relationship between the
      number of mature ovarian follicles and the (multiple) live birth rate after
      controlled ovarian hyperstimulation and intrauterine insemination. STUDY DESIGN:
      A total of 2463 intrauterine insemination cycles performed during a natural cycle
      (n = 118), or after controlled ovarian hyperstimulation with either clomiphene
      citrate (n = 663) or with gonadotrophins (n = 1682) were reviewed to assess the
      impact of the type of stimulation and the number of follicles 14 mm or larger on
      the (multiple) live birth rate per cycle. RESULTS: The live birth rate after
      intrauterine insemination was significantly higher (P = .02) after stimulation
      with gonadotrophins (13%) than after clomiphene cirate (8%) if only 1 follicle 14
      mm or larger was present. If 2 or more follicles were present, there was no
      statistically significant difference between both stimulation methods.
      CONCLUSION: Treatment of intrauterine insemination with gonadotrophin is
      effective with an acceptable (multiple) live birth rate when 1 or 2 follicles 14
      mm or larger are present.

PMID- 18060946
TI  - Comparison of progesterone and glucocorticoid receptor binding and stimulation of
      gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and
      related progestins.
AB  - OBJECTIVE: This study was undertaken to determine whether the reduction in
      premature birth attributable to 17-alpha hydroxyprogesterone caproate occurs
      because of a greater affinity for progesterone or glucocorticoid receptors or by
      enhanced stimulation of progestogen responsive genes when compared with
      progesterone. STUDY DESIGN: We performed competitive steroid hormone receptor
      binding assays using cytosols expressing either recombinant human progesterone
      receptor-A or -B or rabbit uterine or thymic cytosols. We used 4 different
      carcinoma cell lines to assess transactivation of reporter genes or induction of
      alkaline phosphatase. RESULTS: Relative binding affinity of 17-alpha
      hydroxyprogesterone caproate for recombinant human progesterone receptor-B,
      recombinant human progesterone receptor-A, and rabbit progesterone receptors was
      26-30% that of progesterone. Binding of progesterone to rabbit thymic
      glucocorticoid receptors was weak. 17-alpha hydroxyprogesterone caproate was
      comparable to progesterone in eliciting gene expression in all cell lines
      studied. CONCLUSION: Binding to progesterone receptors, glucocorticoid receptors,
      or expression of progesterone-responsive genes is no greater with 17-alpha
      hydroxyprogesterone caproate than with progesterone. Other mechanisms must
      account for the beneficial effect of 17-alpha hydroxyprogesterone caproate on
      preterm birth rates.

PMID- 18060947
TI  - Differential gene expression of somatotrophic and growth factors in response to
      in vivo hypoxia in human placenta.
AB  - OBJECTIVE: Hypoxia-inducible transcription factors (HIFs) have been characterized
      as the most important regulators of O(2)-dependent gene transcription. We
      investigated expression of HIF-dependent growth factors and HIF-independent
      somatotrophic factors in term placenta in response to hypoxic ischemia. STUDY
      DESIGN: Our cross-sectional in vivo analysis included term placentas of
      gestations complicated by the following: (1) birth asphyxia (n = 22); (2) chronic
      hypoxic ischemia (n = 22); and (3) controls (n = 28). Gene expression of leptin,
      insulin-like growth factor (IGF)-1, IGF-2, ghrelin, and human placental growth
      hormone (hPGH) were measured by TaqMan reverse transcriptase-polymerase chain
      reaction. RESULTS: Acute and chronic hypoxia significantly increased leptin
      messenger ribonucleic acid (mRNA) levels, compared with controls (P < .001).
      Augmented IGF-2 mRNA levels were present in chronic hypoxia (P < .001) but not in
      birth asphyxia. IGF-1, ghrelin, and hPGH mRNA levels did not change in relation
      to hypoxia. CONCLUSION: IGF-2 and leptin are suggested to be involved in adaptive
      response to hypoxic ischemia in term placenta with differential transcriptional
      regulation related to the duration of hypoxia.

PMID- 18060948
TI  - Changes in the maternal serum concentration of proearly placenta insulin-like
      growth factor peptides in normal vs abnormal pregnancy.
AB  - OBJECTIVE: The objective of the study was to evaluate maternal serum pro-early
      placenta insulin like (proEPIL) levels during normal and pathologic pregnancy by
      using a newly developed enzyme-linked immunosorbent assay, based on a monoclonal
      antibody designated EPIL15 and directed to the pro-EPIL C-chain 98-108 region.
      STUDY DESIGN: In a group of healthy pregnant women (n = 22), proEPIL peptide
      serum levels were measured longitudinally throughout gestation (8-12, 20-24, and
      30-34 weeks). Serum proEPIL levels were measured in women with preterm labor (n =
      24), intrauterine growth restriction (n = 27), and preeclampsia (n = 12).
      RESULTS: In healthy pregnant women, a significant rise of serum pro-EPIL levels
      (mean +/- SEM) was observed during the third trimester of gestation (30.97 +/-
      2.978 ng/mL; P < .01), with the highest serum levels at 30-34 weeks' gestation (P
      < .001). Serum proEPIL levels were found elevated in women with intrauterine
      growth restriction (107.4 +/- 12.99 ng/mL), preeclampsia (104.8 +/- 36.20 ng/mL),
      or preterm labor (183.8 +/- 36.42 ng/mL) in comparison with levels observed in
      healthy pregnant women (P < .001). CONCLUSION: These results showed that proEPIL
      secretion increases in the last trimester during normal pregnancy and is highly
      secreted in women with pathologic conditions.

PMID- 18060949
TI  - Cytomegalovirus and the role of interferon in the expression of tumor necrosis
      factor-related apoptosis-inducing ligand in the placenta.
AB  - OBJECTIVE: Cytomegalovirus infection causes adverse outcomes during pregnancy.
      Our objective was to determine the role of cytomegalovirus in modulating tumor
      necrosis factor (TNF)-related apoptosis-inducing ligand expression in the
      placenta. STUDY DESIGN: TNF-related apoptosis-inducing ligand messenger RNA and
      protein were quantified in cytomegalovirus-infected placental fibroblasts by
      polymerase chain reaction and enzyme-linked immunosorbent assays, respectively.
      Blocking antibodies against interferon and type I interferon receptor were
      applied to culture medium to characterize the role of type I interferon in
      cytomegalovirus-induced TNF-related apoptosis-inducing ligand upregulation.
      RESULTS: Expression of TNF-related apoptosis-inducing ligand messenger RNA and
      protein was increased in cytomegalovirus-infected placental fibroblasts, compared
      with uninfected controls. The cytomegalovirus-induced TNF-related apoptosis
      inducing ligand messenger RNA upregulation was demonstrated across gestation,
      occurred in the absence of viral gene expression, and required cellular protein
      synthesis. TNF-related apoptosis-inducing ligand messenger RNA upregulation was
      markedly attenuated by inactivation of either type I interferon or its receptor.
      CONCLUSION: One mechanism by which cytomegalovirus infection causes unfavorable
      pregnancy outcomes may involve placental upregulation of TNF-related apoptosis
      inducing ligand via an interferon-mediated pathway.

PMID- 18060950
TI  - Early pregnancy lipid concentrations and spontaneous preterm birth.
AB  - OBJECTIVE: Women who deliver preterm infants may be at increased risk for
      cardiovascular disease, perhaps related to dyslipidemia. STUDY DESIGN: In a
      nested case control study of women with spontaneous preterm birth, cholesterol,
      high-density lipoprotein, low-density lipoprotein, and triglycerides were
      evaluated. Lipid concentrations and gestational changes, as well as risk for
      preterm birth, were evaluated in women who delivered <34 (n = 23), >or=34-<37 (n
      = 67), and >or=37 weeks (n = 199). RESULTS: High cholesterol or triglycerides
      <or=15 weeks were associated with a 2.8-fold (1.0-7.9) and 2.0-fold (1.0-3.9)
      increased risk for preterm birth <34 weeks and >or=34-<37 weeks, respectively.
      Overweight women who delivered <34 weeks had particularly elevated early
      pregnancy concentrations of cholesterol and low-density lipoprotein; lean women
      with moderate preterm birth had elevated triglycerides. There was a reduced
      triglyceride response in the first half of pregnancy among women who delivered
      <34 weeks. CONCLUSION: Our results indicate the presence of dyslipidemia in women
      with spontaneous preterm birth.

PMID- 18060951
TI  - Surgical excision of eroded mesh after prior abdominal sacrocolpopexy.
AB  - OBJECTIVE: We previously described an endoscopic-assisted transvaginal mesh
      excision technique. This study compares surgical outcomes after transvaginal mesh
      excision vs endoscopic-assisted transvaginal mesh excision. In addition, we
      reviewed our postoperative outcomes with excision via laparotomy. STUDY DESIGN:
      This was an inclusive retrospective analysis of patients presenting to our
      institution from 1997 to 2006 for surgical management of vaginal erosion of
      permanent mesh after sacrocolpopexy. Three techniques were utilized:
      transvaginal, endoscopic-assisted transvaginal, and laparotomy. For the patients
      undergoing transvaginal excision, data recorded included number and type of
      excisions performed, number of prior excisions performed at outside facilities,
      intraoperative and postoperative complications (including blood transfusions,
      pelvic abscess, or bowel complications), use of postoperative antibiotics,
      persistent symptoms of vaginal bleeding and discharge at follow-up, and
      demographic characteristics. The intraoperative and postoperative complications
      and the postoperative symptoms were recorded for the laparotomy cases. RESULTS:
      Thirty-one patients underwent transvaginal mesh excision during this time period:
      17 endoscopic-assisted transvaginal and 14 transvaginal without endoscope
      assistance. In addition, a total of 7 patients underwent abdominal excision via
      laparotomy. Comparison of the 2 vaginal methods revealed no difference in the
      demographics or success rate, with success defined as no symptoms at follow-up.
      Endoscopic-assisted transvaginal excision was successful in 7 of 17 patients and
      transvaginal without endoscopic assistance in 9 of 13 patients (1 patient
      excluded for lack of follow-up data) for a total vaginal success rate of 53.3%.
      No intraoperative and only minor postoperative complications occurred with either
      vaginal method. Three patients underwent 3 vaginal attempts to achieve complete
      symptom resolution. The average follow-up time for the entire vaginal group was
      14 months. Seven patients ultimately required abdominal excision and all had
      symptom resolution, however, not without complications. Two patients had bowel
      injury during lysis of adhesions requiring bowel resection in 1 case and repair
      in another, 1 had a postoperative wound infection with breakdown, 1 was
      readmitted for postoperative fever requiring antibiotics, and 1 had an acute
      coronary syndrome requiring transfer to the cardiology service. CONCLUSION:
      Transvaginal excision of mesh with or without endoscopy appears to be a safe and
      less invasive method for excision of eroded vaginal mesh after prior abdominal
      sacrocolpopexy. Up to 3 vaginal excision attempts may be necessary to achieve
      symptom resolution, and complete removal of mesh will likely improve outcomes
      with the transvaginal technique. Although abdominal excision can be considered
      the gold standard for excision of eroded mesh, it is not without potentially
      increased morbidity.

PMID- 18060952
TI  - Sexual function following anal sphincteroplasty for fecal incontinence.
AB  - OBJECTIVE: The objective of the study was to assess sexual function following
      anal sphincteroplasty and determine associations between sexual function and
      fecal incontinence. STUDY DESIGN: Women 1 year or longer following anal
      sphincteroplasty with or without other reconstructive surgery were matched to
      controls. Subjects were mailed the Female Sexual Function Index (FSFI), Fecal
      Incontinence Quality of Life (FIQOL), Fecal Incontinence Severity Index (FISI),
      and a general questionnaire. RESULTS: Twenty-six cases and 26 controls responded;
      73% were sexually active. Sexual function scores were similar between the groups.
      Seventeen sphincteroplasty patients and 8 controls complained of fecal
      incontinence at follow up. Significant correlations were found between FSFI
      domains and the FIQOL depression/self-perception scale, FISI fecal incontinence
      of solid stool, and total FISI. CONCLUSION: Sexual activity and function was
      similar following anal sphincteroplasty, compared with controls, despite worse
      symptoms of fecal incontinence. Fecal incontinence of solid stool and depression
      related to fecal incontinence were correlated with poorer sexual function.

PMID- 18060953
TI  - Pelvic floor symptom changes in pessary users.
AB  - OBJECTIVE: The objective of the study was to compare pelvic floor symptom changes
      in patients who continue vs discontinue pessary use, and determine whether
      changes predict pessary continuation. STUDY DESIGN: Women fitted with pessaries
      completed the Pelvic Floor Distress Inventory-20 (PFDI-20) before and after
      initiating pessary use. Scores were compared in women who continued vs
      discontinued pessaries. Analysis of covariance adjusted for baseline differences
      in scores. Logistic regression and receiver operating characteristic curves were
      used to find a score predicting pessary continuation. RESULTS: Sixty-four women
      had complete follow up data; at 6-12 months, 36 of 64 (56%) continued pessary
      use, and 28 of 64 (44%) discontinued use. The continuation group's final PFDI-20
      total, bladder, and prolapse scale scores were better than the discontinuation
      group's. A 2-month prolapse score that fell to 50% of baseline best predicted
      pessary continuation. CONCLUSION: PFDI-20 scores improved most in women
      continuing pessary use. Pessaries effectively treated urinary symptoms, and most
      effectively treated prolapse symptoms. Prolapse score improvement best predicted
      continued pessary use.

PMID- 18060954
TI  - Sexual function after vaginal surgery for pelvic organ prolapse and urinary
      incontinence.
AB  - OBJECTIVE: The objective of the study was to assess sexual function following
      vaginal surgery and to determine the impact on postoperative sexual function in
      women who undergo concurrent antiincontinence procedures, compared with those who
      do not. STUDY DESIGN: Sexually active women undergoing vaginal repairs for
      prolapse or urinary incontinence were prospectively enrolled. Subjects completed
      the Female Sexual Function Index (FSFI), Urogenital Distress Inventory (UDI-6),
      Incontinence Impact Questionnaire (IIQ-7), and a standardized questionnaire.
      Follow-up occurred at 6 months. RESULTS: Forty-nine subjects (96%) returned their
      postoperative surveys; 48 were sexually active. Improvements were noted in
      postoperative prolapse stage, UDI-6, and IIQ-7. However, sexual function and
      frequency were similar. The most bothersome barrier to sexual activity before
      repair was vaginal bulging; postoperatively it was vaginal pain. Twelve subjects
      (25%) commented on the negative impact of vaginal pain postoperatively. Finally,
      FSFI scores were not different based on performance of antiincontinence surgery.
      CONCLUSION: Sexual function was unchanged following vaginal reconstructive
      surgery despite anatomic and functional improvements; lack of benefit may be
      attributable to postoperative dyspareunia.

PMID- 18060955
TI  - Racial differences in pelvic floor muscle thickness in asymptomatic nulliparas as
      seen on magnetic resonance imaging-based three-dimensional color thickness
      mapping.
AB  - OBJECTIVE: The objective of the study was to compare levator and obturator
      thickness between asymptomatic black and white nulliparas using three-dimensional
      (3D) magnetic resonance imaging (MRI) color mapping. STUDY DESIGN: 3D color
      mapped MRI of pelvic muscles were evaluated in 22 similar nulliparas (12 black,
      10 white). Levator and obturator (OI) were divided into right and left. Levator
      was subdivided into puborectalis (PR) and ileococcygeus (IC) portions. Maximal
      thickness of each muscle was recorded and compared between groups. Nonparametric
      testing was applied, with significance at P = .05. RESULTS: Levator thickness was
      significantly greater in blacks bilaterally (median right PR, 8.5 vs 6.0 mm; P =
      .001; right IC, 6.5 vs 4.5 mm; P = .002; left PR, 9.5 vs 5.75 mm; P = .0002; left
      IC, 6.5 vs 5.75 mm; P = .02). Obturator thicknesses were similar (right OI, 20.0
      vs 19.5 mm; left OI, 19.25 vs 19.25 mm; P = NS). CONCLUSION: Significantly
      thicker levators but similar obturators were seen in black nulliparas, compared
      with white nulliparas. These levator differences may influence pelvic floor
      dysfunction risk. The clinical significance of these findings is under study.

PMID- 18060956
TI  - A randomized, controlled trial evaluating 2 techniques of postoperative bladder
      testing after transvaginal surgery.
AB  - OBJECTIVE: The purpose of this pilot study was to compare the efficacy of 2
      techniques for evaluating bladder function after transvaginal surgery. STUDY
      DESIGN: Subjects scheduled for transvaginal, outpatient surgery were
      consecutively enrolled and randomized to backfill-assisted voiding trial or a
      trial of spontaneous voiding after surgery. RESULTS: Sixty subjects were
      enrolled. The mean time in the perioperative anesthesia care unit for the
      backfill group was 199.5 minutes vs 226.6 minutes in the spontaneous voiding
      group (P = .08). Subjects randomized to backfill were more likely to adequately
      empty their bladders and be discharged home without catheter drainage than
      subjects in the spontaneous voiding group (61.5% vs 32.1%, respectively, P =
      .02). Multiple logistic regression further demonstrated that the backfill
      assisted technique predicted successful bladder emptying after vaginal surgery (P
      = .02). CONCLUSION: Women undergoing transvaginal outpatient surgery are more
      likely to empty their bladder effectively before discharge if they are evaluated
      with a backfill-assisted voiding trial.

PMID- 18060957
TI  - Sexual function before and after sacrocolpopexy for pelvic organ prolapse.
AB  - OBJECTIVE: The objective of the study was to describe sexual function before and
      after sacrocolpopexy. STUDY DESIGN: In the Colpopexy and Urinary Reduction
      Efforts trial, sexual function was assessed in 224 women with sexual partners
      before and 1 year after surgery using validated questionnaires. RESULTS: After
      surgery, significantly fewer women reported sexual interference from "pelvic or
      vaginal symptoms" (32.5% 1 year after surgery vs 7.8% prior to surgery); fear of
      incontinence (10.7% vs 3.3%); vaginal bulging (47.3% vs 4.6%); or pain (39.9% vs
      21.6%). The proportion of women with infrequent sexual desire (32%) did not
      change. More women were sexually active 1 year after surgery (171, 76.3%) than
      before surgery (148, 66.1%). The 11 women (7.4%) who became sexually inactive
      were more likely than sexually active women to report infrequent sexual desire
      (70.0% vs 22.1%, P < .001). The addition of Burch colposuspension did not have an
      impact on postoperative sexual function. CONCLUSION: After sacrocolpopexy, most
      women reported improvements in pelvic floor symptoms that previously interfered
      with sexual function. The addition of Burch colposuspension did not adversely
      influence sexual function.

PMID- 18060958
TI  - Validation of telephone administration of 2 condition-specific quality-of-life
      questionnaires.
AB  - OBJECTIVE: To validate telephone-administered versions of 2 condition-specific
      quality of life questionnaires: Pelvic Floor Distress Inventory and Pelvic Floor
      Impact Questionnaire. STUDY DESIGN: Between December 2005 and September 2006, 55
      women were recruited at their 6-week postpartum visit at a university hospital.
      Written and telephone versions of the 2 questionnaires were completed, with a 2
      week interval between each version. The order of administration was randomized.
      RESULTS: The scores of the written vs telephone versions of the questionnaires
      were not significantly different (PFDI: 9.8 vs 9.0 respectively; P = .36; PFIQ:
      4.4 vs 3.7 respectively; P = .38). These scores were also highly correlated
      (PFDI, r = 0.96 and PFIQ, r = 0.90). CONCLUSION: Telephone administration of
      these instruments is a reliable and accurate measure of the impact of pelvic
      floor disorders and may facilitate clinical and epidemiologic research by
      decreasing cost and improving access to research participants.

PMID- 18060959
TI  - Transobturator tapes for stress urinary incontinence: Results of the Austrian
      registry.
AB  - OBJECTIVE: We established a voluntary registry to collect data on the
      perioperative course of transobturator tape operations for stress incontinence.
      STUDY DESIGN: Forty-seven centers completed a 1-page, 15-item questionnaire per
      procedure. RESULTS: Data on a total of 2543 operations with 11 different tape
      systems were collected. Intraoperative complications were noted for 120
      procedures (4.7%). These included 85 cases of increased bleeding (3.3%), 10
      vaginal perforations (0.4%), 10 bladder perforations (0.4%), and 2 urethral
      perforations. Reoperations attributable to the tape procedure were reported for
      57 patients (24 tapes cut or loosened for voiding dysfunction, 11 vaginal
      erosions, 7 abscesses with erosions). One patient was reoperated at 14 days for a
      retropubic hematoma. There were no reports of bowel or major vessel injuries or
      mortality. Significant postoperative pain was reported for 12 patients (0.5%),
      although this was not specifically asked for in the questionnaire. CONCLUSION:
      Significant complications with transobturator tapes are uncommon. Bladder
      perforations occurred more frequently with outside-in than with inside-out
      techniques. Vaginal erosions, abscesses, and pain may be more common with
      transobturator than with retropubic tapes, and this may be due to the structure
      of the tapes rather than to the route of passage.

PMID- 18060960
TI  - The impact of fecal and urinary incontinence on quality of life 6 months after
      childbirth.
AB  - OBJECTIVE: The objective of the study was to investigate the impact of postpartum
      fecal incontinence (FI) and urinary incontinence (UI) on quality of life (QOL).
      STUDY DESIGN: Seven hundred fifty-nine primiparous women in the Childbirth and
      Pelvic Symptoms study were interviewed 6 months postpartum. FI and UI were
      assessed with validated questionnaires. We measured QOL with SF-12 summary
      scores, health utility index score (a measure of self-rated overall health), and
      the modified Manchester Health Questionnaire. RESULTS: Women with FI had worse
      self-rated health utility index scores (85.1 +/- 9.8 vs 88.0 +/- 11.6, P = .02)
      and Medical Outcomes Study Short Form Health Survey (SF-12) mental summary scores
      (46.8 +/- 9.2 vs 51.1 +/- 8.7, P < .0001) than women without FI or flatal
      incontinence. Women with UI had worse SF-12 mental summary scores (48.3 +/- 9.8
      vs 51.6 +/- 7.8, P < .01) and self-rated health utility index scores (84.1 +/-
      12.5 vs 88.7 +/- 10.1, P < .01) than women without UI. Women with both FI and UI
      had the lowest SF-12 mental summary scores (44.5 +/- 9.0). CONCLUSION: Six months
      after delivery, women experiencing FI or UI reported negative effects on health
      related QOL. FI and UI together have a greater impact than either condition
      alone.

PMID- 18060961
TI  - Effect of host response (incorporation, encapsulation, mixed incorporation and
      encapsulation, or resorption) on the tensile strength of graft-reinforced repair
      in the rat ventral hernia model.
AB  - OBJECTIVE: The objective of the study was to determine whether the elicited
      histologic response to synthetic and xenograft materials affected the tensile
      strength of mesh-reinforced repairs in the rat ventral hernia model. STUDY
      DESIGN: Hernias were repaired with Gynemesh, Pelvicol, Pelvisoft, or Surgisis
      (representing incorporation, encapsulation, mixed incorporation and
      encapsulation, or resorption responses) and were compared with a suture-plicated
      control. Six animals per group were killed at 1 and 3 months after graft
      implantation. Preimplantation tensile strength was also measured for each graft
      material and native rat abdominal wall. RESULTS: Before implantation, Pelvicol
      had significantly higher adjusted tensile strength when compared with the rat
      abdominal wall (P < .001) or the other graft materials (P <or= .05). However, no
      difference in adjusted tensile strength was observed among the groups at 1 and 3
      months after implantation. CONCLUSION: The elicited histologic response did not
      affect the adjusted tensile strength of xenograft or synthetic mesh-reinforced
      repairs when compared with suture controls.

PMID- 18060962
TI  - Patients' pelvic goals change after initial urogynecologic consultation.
AB  - OBJECTIVE: The objective of the study was to determine the effect of initial
      urogynecologic consultation on the number and type of patient goals. STUDY
      DESIGN: Charts of women who underwent initial urogynecology consultation were
      reviewed. Patient goals were collected before and after their consultation.
      Investigators categorized goals into 6 categories. Category and number of goals
      were compared before and after their first visit. Predictors of change and
      clinical associations were assessed. RESULTS: Sixty-three women with a mean age
      of 53 (range, 18-83) years reported a total number of 313 goals. The number of
      patients' postconsultation goals was higher than the number of preconsultation
      goals, (median of 3 +/- 1.2 vs 2 +/- 1.2, respectively; P < .003). Women were
      less likely to report" symptom" and "information-seeking" goals (P < .002 and P <
      .03, respectively) but more likely to report treatment goals after consultation
      (P < .001). CONCLUSION: Urogynecologic consultation affects patients' goals. It
      is important to reassess goals following initial consultation.

PMID- 18060963
TI  - Bowel symptoms in women 1 year after sacrocolpopexy.
AB  - OBJECTIVE: The objective of the study was to evaluate changes in bowel symptoms
      after sacrocolpopexy. STUDY DESIGN: This was a prospectively planned, ancillary
      analysis of the Colpopexy and Urinary Reduction Efforts study, a randomized trial
      of sacrocolpopexy with or without Burch colposuspension in stress continent women
      with stages II-IV prolapse. In addition to sacrocolpopexy (+/- Burch), subjects
      underwent posterior vaginal or perineal procedures (PR) at each surgeon's
      discretion. The preoperative and 1 year postoperative Colorectal-anal Distress
      Inventory (CRADI) scores were compared within and between groups using Wilcoxon
      signed-rank and rank-sum tests, respectively. RESULTS: The sacrocolpopexy + PR
      group (n = 87) had more baseline obstructive colorectal symptoms (higher CRADI
      and CRADI-obstructive scores: P = .04 and < .01, respectively) than the
      sacrocolpopexy alone group (n = 211). CRADI total, obstructive, and
      pain/irritation scores significantly improved in both groups (all P < .01). Most
      bothersome symptoms resolved after surgery in both groups. CONCLUSION: Most bowel
      symptoms improve in women with moderate to severe pelvic organ prolapse after
      sacrocolpopexy.

PMID- 18060964
TI  - Effects of peritoneal closure and suture material on adhesion formation in a
      rabbit model.
AB  - OBJECTIVE: This study was designed to determine whether postoperative adhesions
      to the peritoneum beneath the anterior abdominal wall incision could be decreased
      by peritoneal closure using less reactive suture material. STUDY DESIGN: Six
      longitudinal abdominal incisions were made in each of 16 New Zealand white female
      rabbits. The peritoneum was randomly assigned to nonclosure or closure with
      chromic gut, braided nylon, braided coated polyglactin 910, polydioxanone
      monofilament, or poliglecaprone 25 suture. On postoperative day 14, adhesion
      formation was scored and evaluated microscopically. RESULTS: Peritoneal closure
      decreased adhesion scores, compared with nonclosure, regardless of type of
      suture, and no particular suture was superior. Braided coated polyglactin 910
      resulted in the least chronic inflammation and fibrosis. CONCLUSION: Peritoneal
      closure of peritoneum immediately below laparotomy incisions results in decreased
      adhesion scores, compared with nonclosure in our rabbit model. Adhesion formation
      could not be decreased further using less reactive suture.

PMID- 18060965
TI  - Bladder symptoms 1 year after abdominal sacrocolpopexy with and without Burch
      colposuspension in women without preoperative stress incontinence symptoms.
AB  - OBJECTIVE: The objective of the study was to examine changes in bladder symptoms
      1 year after abdominal sacrocolpopexy (ASC) with vs without Burch
      colposuspension. STUDY DESIGN: Women without stress urinary incontinence (SUI)
      symptoms undergoing ASC were randomized to receive or not receive Burch. One year
      later, irritative, obstructive, and SUI symptoms were assessed in 305 women using
      Urogenital Distress Inventory subscales. A composite "stress endpoint" combined
      SUI symptoms, positive stress test, and retreatment. RESULTS: In all women, the
      mean irritative score decreased from 19.6 +/- 16.3 (mean +/- SD) to 9.1 +/- 10.6;
      for obstructive symptoms, from 34.8 +/- 21.0 to 6.3 +/- 10.4 (both P < .001).
      Preoperative bothersome irritative symptoms resolved in 74.6% (126 of 169) and
      obstructive symptoms in 85.1% (212 of 249), independent of Burch. Fewer women
      with Burch had urge incontinence (14.5% vs 26.8%, P = .048) and fulfilled the
      stress endpoint (25.0% vs 40.1%, P = .012). CONCLUSION: ASC reduced bothersome
      irritative and obstructive symptoms. Prophylactic Burch reduced stress and urge
      incontinence.

PMID- 18060966
TI  - Does supracervical hysterectomy provide more support to the vaginal apex than
      total abdominal hysterectomy?
AB  - OBJECTIVE: The objective of the study was to assess whether cervical preservation
      at the time of hysterectomy may help prevent subsequent apical vaginal vault
      prolapse. STUDY DESIGN: Supracervical hysterectomies were performed in 12
      unembalmed cadavers. Successive hanging weights of 1, 2, 3, and 4 kg were loaded
      against the cervical stump and distances moved were recorded. The same process
      was repeated after completion of a total hysterectomy. RESULTS: Average distances
      pulled with 1, 2, 3, and 4 kg of traction against the cervical stump were 17.8 +/
      1.9, 24.1 +/- 2.5, 29.0 +/- 2.8, and 34.3 +/- 3.5 mm, respectively. After total
      hysterectomy, these distances were 17.5 +/- 2.5, 23.5 +/- 2.6, 29.3 +/- 3.1, and
      34.5 +/- 3.6 mm, respectively. CONCLUSION: In unembalmed cadavers, it appears
      that total abdominal hysterectomy and supracervical hysterectomy provide equal
      resistance to forces applied to the vaginal apex.

PMID- 18060967
TI  - National trends and costs of surgical treatment for female fecal incontinence.
AB  - OBJECTIVE: The objective of the study was to describe national trends, hospital
      charges, and costs of inpatient surgical treatment for female fecal incontinence
      in the United States. STUDY DESIGN: We used the Nationwide Inpatient Sample from
      1998 to 2003 to identify women who underwent surgery for fecal incontinence using
      International Classification of Diseases, ninth revision-CM coding. We examined
      national trends in procedures, patient demographics, outcomes, hospital charges,
      and costs. Multiple linear regression was used to identify variables associated
      with increased costs. RESULTS: A total of 21,547 women underwent inpatient
      surgery for fecal incontinence during the study period. This number has remained
      stable, with 3423 procedures in 1998 and 3509 procedures in 2003. The overall
      risk of complications was 15.4% and the risk of death was 0.02%, which remained
      stable during the study period. Total charges increased from $34 million in 1998
      to $57.5 million in 2003, translating to a total cost of $24.5 million in 2003.
      Variables associated with increased costs included number of procedures per
      admission, length of stay, patient age, and race (P < .05). CONCLUSION: The
      number of women undergoing surgical treatment for fecal incontinence is stable
      but has a significant economic impact on the health care system.

PMID- 18060968
TI  - Patient preparedness: an important predictor of surgical outcome.
AB  - OBJECTIVE: The objective of the study was to determine the influence of patient
      readiness for reconstructive pelvic surgery on surgical outcomes. STUDY DESIGN:
      After undergoing standardized informed consent, consecutive women planning pelvic
      surgery completed a questionnaire assessing their knowledge and readiness for
      surgery pre- and postoperatively. Subjects underwent standardized follow-up 3
      months after surgery, including postoperative satisfaction questionnaire and
      validated condition specific quality of life (QOL) and global improvement scales.
      All subjects had standardized urogynecologic evaluation pre- and postoperatively.
      RESULTS: The 79 women who completed preparedness questionnaires self-rated their
      symptom severity as severe (34%), moderate (58%), and mild (8%). Preparedness was
      associated with postoperative improvement (P = .003), complete satisfaction (P =
      .0005), and improved QOL (P = .02). Objective measures of cure did not differ by
      preparedness. CONCLUSION: Readiness for reconstructive pelvic surgery is
      measurable and associated with patient-perceived surgical outcome. Satisfaction,
      symptom improvement, and QOL are strongly associated with patients' expectations
      and preparedness.

PMID- 18060969
TI  - Long-term follow-up of a transvaginal Burch urethropexy for stress urinary
      incontinence.
AB  - OBJECTIVE: The objective of the study was to describe long-term objective and
      subjective success rates and complications following transvaginal Burch
      urethropexy for stress urinary incontinence. STUDY DESIGN: A case series of 66
      women who underwent vaginal Burch urethropexy for urodynamic stress urinary
      incontinence with urethral hypermobility using a suture carrier device is
      presented. Concurrent prolapse repairs were performed as indicated. RESULTS:
      Sixty-six women (mean age 49.4 +/- 12.1 years) underwent vaginal Burch
      urethropexy. Mean follow-up time was 20.9 +/- 18.9 months. Objective failure was
      observed in 16 patients (24.2%). Subjective failure was reported by 21.2% of
      patients, with 50% and 28.8% reporting success and improvement, respectively. Six
      patients (9%) experienced febrile illness, 4 (6%) experienced intraoperative
      hemorrhage, 1 (1.5%) received transfusion, and 1 (1.5%) experienced pelvic
      abscess. Twelve patients (18.2%) experienced suture erosion; half required
      surgical revision or excision. CONCLUSION: Vaginal Burch urethropexy is generally
      well tolerated but is associated with poor long-term success and high suture
      erosion rates.

PMID- 18060970
TI  - Posterior division of the internal iliac artery: Anatomic variations and clinical
      applications.
AB  - OBJECTIVE: The objective of the study was to characterize the anatomy of the
      internal iliac artery (IIA) and its posterior division branches and to correlate
      these findings to IIA ligation. STUDY DESIGN: Dissections were performed in 54
      female cadavers. RESULTS: Average length of IIA was 27.0 (range, 0-52) mm.
      Posterior division arteries arose from a common trunk in 62.3% (66 of 106) of
      pelvic halves. In the remaining specimens, branches arose independently from the
      IIA, with the iliolumbar noted as the first branch in 28.3%, lateral sacral in
      5.7%, and superior gluteal in 3.8%. The average width of the first branch was 5.0
      (range, 2-12) mm. In all dissections, posterior division branches arose from the
      dorsal and lateral aspect of IIA. The internal iliac vein was lateral to the
      artery in 70.6% (12 of 17) of specimens on the left and 93.3% (14 of 15) on the
      right. CONCLUSION: Ligation of the IIA 5 cm distal from the common iliac
      bifurcation would spare posterior division branches in the vast majority of
      cases. Understanding IIA anatomy is essential to minimize intra-operative blood
      loss and other complications.

PMID- 18060971
TI  - Neurovascular anatomy of the sacrospinous ligament region in female cadavers:
      Implications in sacrospinous ligament fixation.
AB  - OBJECTIVE: The objective of the study was to further characterize the anatomy of
      the coccygeus muscle-sacrospinous ligament (C-SSL) complex and to correlate the
      findings with sacrospinous ligament fixations (SSLF). STUDY DESIGN: Dissections
      were performed in 21 female cadavers. RESULTS: In all dissections, nerves
      originating from S3, S4, S5, or a combination passed over the anterior surface of
      the C-SSL at its midsegment, and either the pudendal or third sacral nerve
      coursed on the superior border of C-SSL at its midpoint. In 100% of specimens,
      the internal pudendal artery (IPA) passed behind or just medial to the ischial
      spine. The average distance of the inferior gluteal artery (IGA) from the ischial
      spine and the superior border of the C-SSL was 24.2 (range, 15-35) mm and 3.4
      (range, 1-5) mm, respectively. CONCLUSION: Nerves to the coccygeus and levator
      ani coursed over the midportion of the C-SSL where SSLF sutures are placed. The
      pudendal nerve and IGA were in proximity to the superior border of the C-SSL at
      its midportion, whereas the IPA passed behind the ischial spine, lateral to the
      recommended site for suture placement.

PMID- 18060972
TI  - Prevalence and risk factors of fecal incontinence in women undergoing stress
      incontinence surgery.
AB  - OBJECTIVE: The objective of the study was to determine the prevalence and
      identify potential risk factors for monthly fecal incontinence (FI) in women
      presenting for stress urinary incontinence (UI) surgery. STUDY DESIGN: From 655
      women enrolled in the Stress Incontinence Surgical Treatment Efficacy Trial,
      baseline data were analyzed. FI was defined as occurring at least monthly.
      Independent variables included sociodemographics, health status and history,
      physical examination, and validated UI questionnaires. Multivariable logistic
      regression models compared women with FI with women with only UI. RESULTS:
      Prevalence of monthly FI was 16%, 10% for liquid stool, and 6% for solid stool.
      In multivariable analysis, increased risk of FI was associated (odds ratio, 95%
      confidence interval) with decreased anal sphincter contraction (4.5, 2.0 to
      10.4), perimenopausal status (2.4, 1.1 to 5.0), prior incontinence
      surgery/treatment (1.8, 1.1 to 2.9), and increased UI bother (1.1, 1.1 to 1.2).
      CONCLUSION: Women enrolled in a stress UI surgical trial have high rates of
      monthly FI and further evaluation of FI symptoms may be warranted.

PMID- 18060973
TI  - Incidence of pelvic floor repair after hysterectomy: A population-based cohort
      study.
AB  - OBJECTIVE: The objective of the study was to assess the incidence of and risk
      factors for pelvic floor repair (PFR) procedures after hysterectomy. STUDY
      DESIGN: Using the Rochester Epidemiology Project database, we tracked the
      incidence of PFRs through June 2006 among 8220 Olmsted County, MN, women who had
      a hysterectomy for benign indications between 1965 and 2002. RESULTS: The
      cumulative incidence of PFR after hysterectomy was 5.1% by 30 years. This risk
      was not influenced by age at hysterectomy or calendar period. Future PFR was more
      frequently required in women who had prolapse, whether they underwent a
      hysterectomy alone (eg, vaginal [hazard ratio (HR) 4.3; 95% confidence interval
      (CI) 2.5 to 7.3], abdominal [HR 3.9; 95% CI 1.9 to 8.0]) or a hysterectomy and
      PFR (ie, vaginal [HR 1.9; 95% CI 1.3 to 2.7] or abdominal [HR 2.9; 95% CI 1.5 to
      5.5]). CONCLUSION: Compared with women without prolapse, women who had a
      hysterectomy for prolapse were at increased risk for subsequent PFR.

PMID- 18060974
TI  - Anatomic relationships of the tension-free vaginal mesh trocars.
AB  - OBJECTIVE: The objective of the study was to describe the distances between the
      major anatomic structures to the path of the tension-free vaginal mesh (TVM)
      trocars. STUDY DESIGN: Four anterior transobturator and 2 posterior ischiorectal
      TVM trocars were inserted bilaterally into 8 fresh frozen cadavers. Dissections
      were performed and mean distances (95% confidence interval) were measured between
      the closest points along the trocar's path and significant anatomic structures.
      RESULTS: The mean distances between both anterior transobturator trocars and the
      medial branch of the obturator vessels were 0.8 cm (range, 0.6 to 1.0) and 0.7 cm
      (range, 0.4 to 1.1), and bladder were 0.7 cm (range, 0.5 to 0.9) and 1.3 cm
      (range, 0.8 to 1.9), respectively. The mean distances between the posterior
      trocar and the rectum and inferior rectal vessels were 0.8 cm (range, 0.6 to 1.0)
      and 0.9 cm (range, 0.7 to 1.1), respectively. CONCLUSION: The bladder and medial
      branch of the obturator vessel may be at risk of injury during the passage of the
      anterior trocars, whereas the rectum and inferior rectal vessels may be at risk
      during the passage of the posterior trocar.

PMID- 18060975
TI  - Anatomic relationships of the distal third of the pelvic ureter, trigone, and
      urethra in unembalmed female cadavers.
AB  - OBJECTIVE: The objective of the study was to examine the relationship of the
      ureter to paravaginal defect repair (PVDR) sutures and to evaluate the anatomy of
      distal ureter, trigone, and urethra relative to the anterior vaginal wall. STUDY
      DESIGN: Dissections of the retropubic space were performed in 24 unembalmed
      female cadavers following placement of PVDR sutures. Lengths of the vagina,
      urethra, and trigone were recorded. RESULTS: The mean distance between apical
      PVDR sutures and the ureter was 22.8 (range, 5-36) mm. The average lengths of the
      urethra, trigone, and vagina were 3 cm, 2.8 cm, and 8.4 cm, respectively. The
      trigone was positioned over the middle third of the anterior vaginal wall in all
      specimens and the distal ureters traversed the anterolateral vaginal fornices.
      CONCLUSION: The ureters may be injured during paravaginal defect repairs,
      anterior colporrhaphies, and other procedures involving dissection in the upper
      third of the vagina. Cystotomy during vaginal hysterectomies is most likely to
      occur 2-3 cm above the trigone.

PMID- 18060976
TI  - Vaginal paravaginal repair with an AlloDerm graft: Long-term outcomes.
AB  - OBJECTIVE: The aim of this study was to describe the long-term objective and
      subjective outcomes after vaginal paravaginal repair with AlloDerm graft
      (LifeCell, Branchburg, NJ). STUDY DESIGN: Thirty-three women with either
      recurrent stage II or primary or recurrent stage III-IV anterior vaginal wall
      prolapse underwent a vaginal paravaginal repair with AlloDerm graft between
      November 1998 and April 2002. Postoperative follow-up was obtained on an annual
      basis. Objective failure was defined as a stage II or greater anterior wall
      defect. Descriptive statistics were performed. RESULTS: Long-term follow-up was
      obtained on 24/33 subjects (72.7%). The mean length of follow-up for the 24 women
      was 52.0 months (range, 18-86 months). Fourteen of the 24 subjects (58.3%) had
      recurrent stage II prolapse in the anterior compartment, of which only 4 of 14
      (28.6%) were symptomatic. CONCLUSIONS: Long-term evaluation of vaginal
      paravaginal repairs with AlloDerm graft reveals good subjective success, despite
      a moderate rate of objective failure within the first 24 months.

PMID- 18060977
TI  - Uterosacral ligament suspension sutures: Anatomic relationships in unembalmed
      female cadavers.
AB  - OBJECTIVE: The objective of the study was to characterize anatomic relationships
      of uterosacral ligament suspension (USLS) sutures. STUDY DESIGN: The relationship
      of USLS sutures to the ureters, rectal lumen, and sidewall neurovascular
      structures was examined in 15 unembalmed female cadavers. RESULTS: The mean
      distance of the proximal sutures to the ureters and rectal lumen was 14 mm
      (range, 0-33) and 10 mm (range, 0-33), respectively. The mean distance of the
      distal sutures to the ureters was 14 mm (range, 4-33) and to the rectal lumen 13
      mm (range, 3-23). Right sutures were noted at the level of S1 in 37.5%, S2 in
      37.5%, and S3 in 25% of specimens. Left sutures were noted at the level of S1 in
      50%, S2 in 29.2%, and S3 in 20.8% of cadavers. Of 48 sutures passed, 1 entrapped
      the S3 nerve. Sutures perforated the pelvic sidewall vessels in 4.1% of
      specimens. CONCLUSION: USLS sutures can directly injure the ureters, rectum, and
      neurovascular structures in the pelvic walls.

PMID- 18060978
TI  - Informed consent in gynecologic surgery.
AB  - OBJECTIVE: The objective of the study was to describe surgeon self-reported
      behaviors and descriptions of information given to patients when obtaining
      surgical consent. STUDY DESIGN: This was a survey of 330 gynecological surgeons.
      Surgeons rated descriptions of information given to patients as well as behaviors
      for confirming patient understanding during surgical consent. Mean ratings are
      compared with repeated-measures multivariate analysis of variance. RESULTS: Forty
      four percent of surveys (145 of 330) were returned. Most respondents were male
      (56%), Caucasian (86%), in academic practices settings (55%), with more than 10
      years of experience after residency (53%). Surgeons give very detailed
      descriptions of risks and alternatives to surgery. Less detailed descriptions are
      given of the postoperative course, expected benefits of surgery, or functional
      and anatomic changes after surgery. Surgeons confirm patient understanding most
      often by asking patients whether they have any questions and rarely evaluate
      patient literacy. CONCLUSION: Surgeons provide widely varying attention to
      various issues and topics related to communicating with their patients
      preoperatively.

PMID- 18060979
TI  - Relationship among surgical complexity, short-term morbidity, and overall
      survival in primary surgery for advanced ovarian cancer.
AB  - BACKGROUND: Advanced ovarian cancer (OC) is associated with impaired performance
      status and comorbidities for many patients. These factors have an impact on the
      decision to perform extended surgical cytoreduction. However, the trade-off
      between short-term morbidity and overall survival is complex, and few data are
      available analyzing the combined effects of these variables. PURPOSE: The purpose
      of the study was to evaluate the impact of patients' age and American Society of
      Anesthesiologists (ASA) and surgical complexity score (SCS) on short-term
      morbidity and overall survival. STUDY DESIGN: Presurgical patient
      characteristics, surgical procedures performed, and outcomes were assessed in a
      cohort of consecutive primary OC patients. An SCS from 1 to 3 was developed to
      adjust for the extent of surgery (simple to complex, respectively). Primary
      outcomes were 30 day major morbidity (sepsis, thromboembolic, cardiac, or
      reoperation), 3 month mortality, and overall survival (OS). RESULTS: Two hundred
      nineteen consecutive patients with stage IIIC-IV OC were included. We observed a
      correlation between ASA and both short-term morbidity (P = .006) and 3 month
      mortality (P = .006). Age was independently associated with both short-term
      morbidity (P = .010) and 3 month mortality (P = .005). SCS correlated directly
      with morbidity (P < .001) but was not correlated with mortality (P = .266). The
      independent predictors of morbidity (ASA, age, and SCS) were used to develop risk
      prediction categories: risk of expected complications ranged from 2.5% to 67.6%,
      depending on category. Despite the increased risk of complications, however, more
      complex surgery carried a survival benefit in all the risk groups, owing to the
      observation that residual disease (RD) and SCS held a prognostic significance
      independent of age and ASA (P < .001 and P = .001, respectively). CONCLUSION:
      Because of the survival benefit from lower RD, a less aggressive surgical effort
      results in poorer OS. However, the risk of complications are substantial for
      complex surgeries in the highest-risk patients: risk stratification should be
      used to help plan perioperative care and consider optimal treatment planning.

PMID- 18060980
TI  - Where to look for the sentinel lymph node in cervical cancer.
AB  - OBJECTIVE: The aim of this study was to analyze lymphatic spread to pelvic,
      parametrial, and paraaortic lymph nodes in patients with cervical cancer. STUDY
      DESIGN: We reviewed 619 patients with invasive cervical cancer treated by radical
      abdominal hysterectomy and systematic pelvic or pelvic and paraaortic
      lymphadenectomy between 1971 and 2005. The present study included 61 patients
      with one positive lymph node (10%) and 59 patients with two positive lymph nodes
      (10%) at any location. RESULTS: The external iliac (43%) and obturator (26%)
      regions and the parametrium (21%) were the most commonly involved pelvic lymph
      node sites with solitary metastases. Isolated metastases to common iliac,
      presacral (internal iliac), and paraaortic nodes were found in 7%, 1%, and 1% of
      patients, respectively. Patients with 2 positive nodes had 1 parametrial and 1
      pelvic node involved (32%), 2 ipsilateral positive nodes (31%), 1 positive lymph
      node on both sides of the pelvis (27%), and 2 positive nodes within the
      parametrium (10%). CONCLUSIONS: In cervical cancer patients with only 1 positive
      lymph node, this node is most frequently located within the external iliac and
      obturator regions and the parametrium. Sentinel node identification should
      primarily address these lymph node sites. If 1 positive lymph node is found,
      further metastases are unpredictable within pelvic and parametrial lymph node
      sites. Paraaortic spread without pelvic node involvement is rare.

PMID- 18060981
TI  - Impact of age on preoperative and postoperative urinary incontinence quality of
      life.
AB  - OBJECTIVE: The objective of the study was to estimate the effect of age on
      quality of life in women with urinary incontinence before and following
      antiincontinence surgery. STUDY DESIGN: We performed a retrospective cohort study
      of women who underwent surgery for stress urinary incontinence from December 2003
      to August 2005. Younger women were defined as age younger than 60 years and older
      women were defined as age 60 years or older. Quality of life was measured using
      Incontinence Impact Questionnaire (IIQ)-7 and Urogenital Distress Inventory (UDI)
      6 questionnaires pre- and postoperatively. Multiple linear regression was
      performed to estimate the effect of age on improvement in quality-of-life scores.
      RESULTS: One hundred sixty-eight younger women and 81 older women were included.
      Older women had lower mean baseline IIQ-7 scores (P < .01) and had less
      improvement in IIQ-7 scores postoperatively (P = .02) when compared with younger
      women. After adjusting for baseline IIQ-7 score using multiple linear regression,
      age was no longer associated with decreasing improvements in quality-of-life
      scores following surgical treatment. CONCLUSIONS: Antiincontinence surgery is
      associated with improved quality of life in both older and younger women.

PMID- 18060983
TI  - A successful break-up.

PMID- 18060984
TI  - Progesterone to prevent preterm delivery: Enigma or ready?

PMID- 18060986
TI  - Lower uterine segment varices: Significance and management.

PMID- 18060988
TI  - Risk factors for primary and subsequent anal sphincter lacerations: A comparison
      of cohorts by parity and prior mode of delivery.

PMID- 18060994
TI  - Atrial fibrillation: a historical perspective.
AB  - Atrial fibrillation (AF) undoubtedly has become one of the most well studied
      arrhythmias today in terms of pathophysiology and diagnostic and therapeutic
      (interventional) electrophysiology. Although it lends itself to an apparently
      easy diagnosis on a surface ECG, myriad electromechanical mechanisms underlie its
      origin. An era of technology has been reached that makes AF not only "treatable"
      but also potentially "curable." This article aims at walking through the
      historical corridors and maze that have led to the present-day understanding of
      this most common yet complex arrhythmia.

PMID- 18060995
TI  - Status of the epidemiology of atrial fibrillation.
AB  - Atrial fibrillation (AF), an increasingly common dysrhythmia, is responsible for
      substantial morbidity and mortality. Currently in the United States,
      approximately 2.3 million people are diagnosed with AF and, based on the census,
      this number may rise to 5.6 million by 2050. Risk factors for AF include
      advancing age and cardiovascular disease and its risk factors. The chief hazard
      of AF is embolic stroke, which is increased four- to fivefold, assuming great
      importance in advanced age when it becomes a dominant factor. AF is associated
      with about a doubling of mortality.

PMID- 18060996
TI  - Genetics of atrial fibrillation.
AB  - Recent studies of atrial fibrillation (AF) have identified mutations in a series
      of ion mutations; however, these channels appear to be relatively rare causes of
      AF. Recent genome-wide association studies for AF have identified novel variants
      associated with the disease, although the mechanism of action for these variants
      remains unknown. Ultimately, a greater understanding of the genetics of AF should
      yield insights into novel pathways, therapeutic targets, and diagnostic testing
      for this common arrhythmia.

PMID- 18060998
TI  - Diagnosis and management of typical atrial flutter.
AB  - Can "past decade" be rephrased to refer to more specific years? Typical atrial
      flutter (AFL) is a common atrial arrhythmia that may cause significant symptoms
      and serious adverse effects, including embolic stroke, myocardial ischemia and
      infarction, and, rarely, a tachycardia-induced cardiomyopathy resulting from
      rapid atrioventricular conduction. As a result of the well-defined anatomic and
      electrophysiologic substrate and the relative pharmacologic resistance of typical
      AFL, radiofrequency catheter ablation has emerged since its first description in
      1992 as a safe and effective first-line treatment. This article reviews the
      electrophysiology of typical AFL and techniques currently used for its diagnosis
      and management.

PMID- 18060997
TI  - New concepts in atrial fibrillation: mechanism and remodeling.
AB  - Atrial fibrillation (AF) is a complex disease with many possible mechanisms.
      Studies indicate that the arrhythmogenic foci within the thoracic veins are AF
      initiators. Once initiated, AF alters atrial electrical and structural properties
      in a way that promotes its own maintenance and recurrences and may alter the
      response to antiarrhythmic drugs. The exact mechanisms by which the initiators
      trigger AF remain elusive, however. Evidence to date suggests that autonomic
      modulation does have an adjunctive role to play in catheter AF ablation,
      especially when applied selectively. Further mechanistic and clinical studies are
      warranted before a wider application can be recommended.

PMID- 18060999
TI  - Postoperative atrial fibrillation.
AB  - Atrial fibrillation is a common arrhythmia after cardiac surgery. It is
      associated with an increase in morbidity, length of hospital stay, and mortality.
      Patients who are at higher risk of postoperative atrial fibrillation should
      receive prophylactic treatment. Atrial fibrillation usually resolves
      spontaneously after heart rate is controlled; however, if patients are highly
      symptomatic or hemodynamically unstable, sinus rhythm should be restored by
      electrical or pharmacologic cardioversion. Patients with atrial fibrillation of
      more than 48 hours should receive antithrombotic therapy for thromboembolism
      prevention.

PMID- 18061000
TI  - Electrical and pharmacologic cardioversion for atrial fibrillation.
AB  - In this article, electrical and pharmacologic cardioversion for atrial
      fibrillation is described in detail. Indications for cardioversion and management
      of pericardioversion anticoagulation also are discussed. Finally, management
      strategies for immediate recurrence of atrial fibrillation and cardioversion
      failure are offered.

PMID- 18061001
TI  - Drug therapy for atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia. Prevalence
      increases with age, and the overall incidence is expected to increase as the
      population continues to age. Choice of pharmacologic therapy for atrial
      fibrillation depends on whether or not the goal of treatment is maintaining sinus
      rhythm or tolerating atrial fibrillation with adequate control of ventricular
      rates. New antiarrhythmic drugs are being tested in clinical trials. Drugs that
      target remodeling and inflammation are being tested for their use as prevention
      of AF or as adjunctive therapy.

PMID- 18061002
TI  - Anticoagulation: stroke prevention in patients with atrial fibrillation.
AB  - It is well recognized that during atrial fibrillation (AF), clots may form in the
      left atrium. This, in turn, may lead to embolization of the clot, with resulting
      ischemic stroke or systemic embolism. Also, the presence of AF confers a fivefold
      increased risk for stroke. AF is the most common and important cause of stroke
      resulting from any cause. This article considers the risks for and
      anticoagulation prophylaxis against embolic stroke in patients with AF.

PMID- 18061003
TI  - The role of pacemakers in the management of patients with atrial fibrillation.
AB  - Pacemakers have an important role in the major strategies for the management of
      atrial fibrillation, rate control and rhythm control. Of all the current non
      pharmacologic therapies for atrial fibrillation, the use of pacemakers impacts
      the largest number of patients. Pacemakers are used to facilitate medical
      management of atrial fibrillation with rate control agents and anti-arrhythmic
      drugs. Atrioventricular junction ablation in conjunction with pacemaker
      implantation can be an effective therapy for controlling a rapid ventricular rate
      during atrial fibrillation. The minimization of right ventricular apical pacing
      in patients with paroxysmal atrial fibrillation is an important objective.
      Cardiac resynchronization therapy devices are likely to be beneficial in select
      patients with chronic atrial fibrillation.

PMID- 18061004
TI  - Catheter ablation of atrial fibrillation.
AB  - Atrial fibrillation is a common arrhythmia associated with significant morbidity
      including angina, heart failure and stroke. Medical therapy remains suboptimal
      with significant side effects and toxicities, as well as a high recurrence rate.
      Catheter ablation or modification of the atrio-ventricular node with pacemaker
      implantation provides rate control but subjects the patient to the risks of an
      implantable device and does nothing to reduce the risk of stroke. Pulmonary vein
      antrum isolation offers a nonpharmacologic means of restoring sinus rhythm,
      thereby eliminating the morbidity of atrial fibrillation and the need for anti
      arrhythmic drugs.

PMID- 18061005
TI  - Surgical approaches for atrial fibrillation.
AB  - For cardiac surgery patients presenting with atrial fibrillation (AF), surgeons
      offer an operation that corrects the structural heart disease and the AF. With
      this approach, it is estimated that surgeons will perform more than 10,000
      ablation procedures in 2007. Surgeons are developing minimally invasive
      techniques for stand-alone, epicardial ablation of AF. This article (1) reviews
      the rationale for surgical ablation of AF, (2) describes the classic maze
      procedure and its results, (3) details new approaches to surgical ablation of AF,
      (4) emphasizes the importance of management of the left atrial appendage, and (5)
      considers challenges and future directions in the ablation of AF.

PMID- 18061006
TI  - Atrial fibrillation: goals of therapy and management strategies to achieve the
      goals.
AB  - The primary goals in the management of patients who have atrial fibrillation are
      prevention of stroke and cardiomyopathy and amelioration of symptoms. Each
      patient presents to a physician with a specific constellation of symptoms and
      signs, but, fortunately, most patients can be assigned to broad categories of
      therapy. For some, anticoagulation and rate control suffice, whereas others
      require more aggressive attempts to restore and maintain sinus rhythm. Physicians
      and patients need to be willing to alter therapeutic plans if an initial strategy
      of rate or rhythm control is unsuccessful.

PMID- 18061007
TI  - Atrial fibrillation: unanswered questions and future directions.
AB  - Just more than a decade ago, Haissaguerre and colleagues provided the seminal
      demonstration of the role of pulmonary vein triggers in the pathogenesis of
      atrial fibrillation (AF) and the potential therapeutic role of catheter ablation
      to treat patients who have paroxysmal AF. This initial observation ushered in the
      modern era of catheter ablation to treat patients who have AF, and tremendous
      progress has been made in understanding its pathogenesis and the catheter
      approaches to treating this rhythm. Although the current state of AF catheter
      ablation is well described earlier in this issue, this article reflects on some
      of the major unanswered questions about AF management, and the future
      technological and investigational directions being explored in the
      nonpharmacologic management of AF.

PMID- 18061008
TI  - Managing polarities in complex systems.

PMID- 18061009
TI  - Re: Image of the nurse on the Internet.

PMID- 18061010
TI  - President's message. An update of the American Academy of Nursing's activities in
      support of our strategic goals.

PMID- 18061011
TI  - An alternative model for postdoctoral education of nurses engaged in research
      with potentially vulnerable populations.
AB  - Post-doctoral education has become a necessity for new nursing doctoral
      graduates. However, post-doctoral positions are limited and nurse scientists may
      face barriers that make non-traditional programs necessary. This study describes
      the outcomes of the Summer Nursing Research Institute (SNRI), an alternative post
      doctoral educational program, reports formative perceptions of SNRI participants,
      and illustrates the efficacy and limitations of the model with selected summative
      research related outcomes. Participants between 1997 and 2006 were asked to
      evaluate the experience while attending the Institute (formative evaluation) and
      an overall summative evaluation was also conducted. Evaluations indicate that
      participants gained knowledge, skills, and networking abilities in terms of
      conducting research with vulnerable populations. A program like the SNRI can be
      successful in widening the research pipeline, in imparting knowledge, and in
      fostering positive attitudes as well as in improving research skills.

PMID- 18061012
TI  - Outcomes assessment of clinical information system implementation: a practical
      guide.
AB  - Healthcare information systems (HIS) play a vital role in quality of care and the
      organization's daily operations. Consequently, increasing numbers of clinicians
      have been involved in HIS implementation, particularly for clinical information
      systems (CIS). Implementation of these systems is a major organizational
      investment, and its outcomes must be assessed. The purpose of this article is to
      provide clinicians and frontline informaticians with a practical guide to assess
      these outcomes, focusing on outcome variables, assessment methods, and timing of
      assessment. Based on in-depth literature reviews and their empirical experiences,
      the authors identified 3 frequently used outcomes: user satisfaction, clinical
      outcomes, and financial impact. These outcomes have been assessed employing
      various methods, including randomized controlled trials, pre- and post-test
      studies, time and motion studies, surveys, and user testing. The timing for
      outcomes assessments varied depending on several factors, such as learning curves
      or patients conditions. In conclusion, outcomes assessment is essential for the
      success of healthcare information technology, and the CIS implementation team
      members must be prepared to conduct and/or facilitate these studies.

PMID- 18061013
TI  - Characteristics of schools of nursing operating academic nurse-managed centers.
AB  - Academic nurse-managed centers (ANMCs) can be important sites for addressing the
      tripartite mission of the academy. Yet, limited information about numbers of
      ANMCs and the schools sponsoring them is available. This paper presents an update
      on schools of nursing (SONs) operating ANMCs. A survey was sent to 683 deans and
      directors of baccalaureate and higher-degree SONs, with 565 responding (response
      rate: 83%). Ninety-two SONs indicated they had one or more ANMCs. The largest
      percentage of the SONs with ANMCs were classified as doctoral/research-intensive
      or extensive universities, a proportion much higher than the national percent of
      SONs in this category. Schools of Nursing were financially supporting centers at
      a lower percentage of actual costs than was reported in earlier studies, although
      grants continue to be a major source of funding. Academic nurse-managed centers
      are likely to be supported by SONs with substantial research, practice, faculty,
      and student resources. Overall, the national number of ANMCs seems stationary
      over the past two decades.

PMID- 18061014
TI  - Differences in universal diverse orientation among nursing students in Australia.
AB  - With globalization and intensified migration, an attitude of awareness and
      acceptance of both similarities and differences among people-known as universal
      diverse orientation (UDO)-is a positive benefit that students may bring to a
      nursing program. Using a cross-sectional survey design, this study measured
      students' UDO using the Miville-Guzman Universality-Diversity Scale-Short Form (M
      GUDS-S). Among 816 nursing students, those born in a non-English-speaking country
      had higher M-GUDS-S scores (P < 0.001), and those who spoke both English and non
      English at home had consistently higher scores in all three M-GUDS-S subscales.
      However, those who never spoke English at home had low scores in the "Comfort
      with Differences" subscale if they had lived in Australia for only a few years.
      Nursing students from a non-English-speaking background could potentially enrich
      cross-cultural educational experiences for all students, but students who have
      recently settled in Australia may need support to feel a sense of connectedness.

PMID- 18061015
TI  - Graduate education in geropsychiatric nursing: findings from a national survey.
AB  - By 2030, the numbers of older adults with mental illness will strain our health
      care system. Sufficient advanced practice nurses (APNs) with specialized
      knowledge to provide care will be critical. All 339 graduate nursing programs in
      the US were surveyed regarding the extent and nature of geropsychiatric nursing
      (GPN) content in their curricula. Of 206 schools responding, 15 reported having a
      GPN subspecialty. Regarding the 60 schools with a psychiatric/mental health
      nursing (PMHN) graduate program, only one third (n = 23) included some GPN
      content, while more than half (n = 116) of all schools reported integration of
      GPN content in a non-psychiatric nurse practitioner program. Thus, currently, the
      greatest numbers of APNs receiving education on mental health needs of older
      adults are prepared in non-psychiatric nurse practitioner programs. This article
      discusses the implications for nursing education and practice.

PMID- 18061016
TI  - The assessment and documentation of language and communication needs in
      healthcare systems: current practices and future directions for coordinating
      safe, patient-centered care.
AB  - Several issues surface when one considers the task of unpacking health
      disparities and examining features of health care systems that influence patient
      access, utilization, and outcomes. Although progress has been made in the
      collection of language data across healthcare systems, little attention has been
      devoted to examining how a patient's English proficiency and the need for
      interpretation services are being determined, and how this information is
      communicated to providers. A lack of a standardized approach to these system
      based processes exposes potential limitations in the ability of systems and
      providers to effectively coordinate care that meets patients' needs and minimizes
      disparate outcomes. Attention must be given to standardizing these processes to
      ensure safe, patient-centered care and enable meaningful analyses of access,
      utilization, and outcomes across linguistically diverse populations. Nurses play
      a key role in developing and evaluating information systems with which accurate
      and reliable data can be collected, documented, retrieved, and utilized.

PMID- 18061017
TI  - Evaluating work ability and quality of life for clinical nurses in Taiwan.
AB  - This study investigated the work ability and its relationship with quality of
      life for the clinical nurses in Taiwan. The survey was of 1534 nursing
      professionals from 8 different hospitals. Work ability of nursing professionals
      varied by age, work experience, working departments and hospital types. Work
      ability of nurses increased with age until after the age of 45. Personal health
      condition and physical workload were the main factors contributing to the decline
      of the perceived work ability for senior nurses. For young nurses, the mental
      demands of work were a critical influence on their work ability. Moreover, work
      ability of nurses varied among hospital type and department. The work ability of
      nurses was strongly associated with the quality and safety of the work
      environment and leisure time management. For improving and maintaining the work
      ability of nurses, countermeasures such as enhancing the ability to cope with the
      job's mental demands for young nurses, and improving the job design to reduce
      physical workload for senior nurses are recommended.

PMID- 18061019
TI  - Uncomplicated urinary tract infection in adults including uncomplicated
      pyelonephritis.
AB  - Acute uncomplicated urinary tract infection and acute pyelonephritis are very
      common infections affecting many women throughout their lives. The determinants
      of infection have been well described and current strategies to prevent recurrent
      infections are highly effective. While antimicrobial management is
      straightforward for most episodes, the evolution of antimicrobial susceptibility
      of E. coli in community-acquired infection requires continuing re-evaluation of
      appropriate empiric therapy.

PMID- 18061020
TI  - Complicated urinary tract infections.
AB  - A complicated urinary tract infection is that which occurs in a patient with an
      anatomically abnormal urinary tract or significant medical or surgical
      comorbidities. Whereas this definition may not cover each and every situation, it
      does serve to encompass the great majority of these patients and guide their
      care. The definition is necessarily broad, to assure that these potentially
      complex patients are appropriately managed. Thus, complicated urinary tract
      infection describes a group of patients that usually need a prolonged course of
      antimicrobial therapy, with all its attendant morbidities, costs, and outcome
      differences.

PMID- 18061021
TI  - Bacterial prostatitis.
AB  - Prostatitis is perhaps the most common urologic complaint in men younger than 50
      years of age and affects 11% to 16% of American men over the course of their
      lifetimes. Prostatitis syndromes have a significant psychologic impact upon
      patients who suffer from them and place an enormous financial strain upon the
      health care system. Despite many advances in our understanding of the
      pathogenesis and treatment of prostatitis, current management strategies are
      unable to provide a significant portion of relief from symptoms. In this article,
      we focus on bacterial prostatitis (types I and II), with an emphasis on new
      understandings of pathogenesis, diagnosis, and treatment strategies for these
      often challenging patients.

PMID- 18061022
TI  - Sexually transmitted infections.
AB  - This article addresses the importance of screening for sexually transmitted
      diseases as a form of secondary prevention. The differential diagnoses of genital
      ulcers or inflammatory disorders of the genitourinary tract, with a higher index
      of suspicion for sexually transmitted disease, are discussed, as well as
      currently recommended treatment options for the same.

PMID- 18061023
TI  - New developments in the diagnosis and management of pediatric UTIs.
AB  - Urinary tract infections (UTIs) in children are common and a major source of
      morbidity. The incidence of UTIs in childhood is not precisely known because it
      is not a reportable disease, and in many cases, especially in infants, UTIs are
      underdiagnosed. Furthermore, the definitions and criteria for diagnosis vary
      considerably. This article reviews the diagnosis and work-up of UTIs in children,
      and presents current data reviewing the roles of radiologic imaging, surgical
      correction, and antibiotic prophylaxis in the setting of pediatric UTIs.

PMID- 18061024
TI  - HIV-AIDS: urologic considerations.
AB  - The prevalence of HIV continues to grow in the United States and worldwide. HIV
      positive patients experience many genitourinary disease processes. With
      improvements in HIV therapy, patients have questions and concerns pertaining to
      their quality of life. This article reviews conditions such as HIV-related
      urinary tract infections, urolithiasis, voiding dysfunction, fertility, sexual
      dysfunction, HIV-related nephropathy, malignancies, and occupational exposure and
      prophylaxis. Knowledge of the various HIV manifestations of genitourinary
      conditions and their treatment options benefits clinicians and improves patient
      outcomes.

PMID- 18061025
TI  - Antibiotics in urology: new essentials.
AB  - The bacterial spectrum and rates of antimicrobial resistance of uncomplicated
      community-acquired and complicated and nosocomially acquired urinary tract
      infections differ substantially. Significant variation exists from region to
      region and over time. On the other hand, antibiotics are widely used in urologic
      practice for the need of modern medicine; therefore, antibiotic substances are
      continuously evaluated for clinical usage. The use of antibiotics must keep up
      with continuous changes in antimicrobial resistance and be tailored to the needs
      of individual patients.

PMID- 18061026
TI  - Chronic prostatitis/chronic pelvic pain syndrome.
AB  - In the 20th century, the term "prostatitis" traditionally referred to
      inflammation in the prostate, often attributed to infection. Prostatitis in this
      century usually refers to a chronic pain syndrome for which the presence of
      inflammation and involvement of the prostate are not always certain. This article
      discusses chronic prostatitis/chronic pelvic pain syndrome and the various
      factors associated with diagnosis and treatment.

PMID- 18061027
TI  - Re-imagining interstitial cystitis.
AB  - Since the postulation of an "antiproliferative factor" in 1998 and a description,
      six years later, of this putative central protein in the etiologic pathway of the
      painful bladder syndrome/interstitial cystitis, there have been no dramatic
      breakthroughs in the field. Although much potentially exciting work is in
      progress with regard to epidemiology, etiology, and clinical treatment, many
      clinicians and researchers have used this hiatus to take another look at what
      exactly is being studied and how the syndrome should be approached. This article
      explores some of the current "hot-button" issues of definition and nomenclature
      that have formed the basis of many international meetings in the last 5 years.

PMID- 18061028
TI  - Diagnosis and management of epididymitis.
AB  - Epididymitis is a common and morbid condition seen across a wide age range. There
      are multiple etiologies that may lead to inflammation of the epididymis,
      including infection, trauma, autoimmune disease, and vasculitis. Although there
      have been multiple advances in imaging of the scrotum and detection of urinary
      pathogens, a large portion of cases remain idiopathic. Management of epididymitis
      is often difficult, but relies on clinical expertise and the use of established
      clinical guidelines.

PMID- 18061029
TI  - Inflammation and benign prostatic hyperplasia.
AB  - Prostatitis, a histologic diagnosis, has evolved over the years to describe a
      clinical syndrome that was believed to be associated with prostatic inflammation.
      Similarly, benign prostatic hyperplasia (BPH), another histologic diagnosis, has
      evolved to describe a clinical syndrome believed to be associated with prostatic
      enlargement. Recent explorations of the interrelationships between these prostate
      associated histologic and clinical conditions have generated much interest and
      excitement. This article describes these relationships and their impact on the
      management of, in particular, BPH.

PMID- 18061030
TI  - Inflammation and prostate cancer: a future target for prevention and therapy?
AB  - Given its long natural history, prostate cancer has become an ideal model for the
      clinical and basic science study of neoplastic disease in distinct pathologic
      phases: tumor initiation, progression, invasion, and metastasis. Chronic or
      recurrent acute inflammation, a product of infectious agents or other sources,
      has potential promotional roles in each of these phases. Nonsteroidal anti
      inflammatory drugs (NSAIDs), because of their ability to attenuate inflammation,
      as well as possibly direct anti-cancer properties associated with the inhibition
      of stromal cyclooxygenase-2, are potential candidates for clinical use in
      prostate cancer. Though epidemiologic evidence indicating a reduced risk of
      prostate cancer for NSAID users supports a chemoprotective benefit, observational
      assessment and clinical trials of these agents among large cohorts of prostate
      cancer patients are needed to determine their value in prostate cancer
      management.

PMID- 18061035
TI  - The ethics of public health.

PMID- 18061036
TI  - Timeout, not the final buzzer, in the stem cell debate.

PMID- 18061037
TI  - Global HIV/AIDS estimates--looking beyond the numbers.

PMID- 18061038
TI  - The paradox of cholesterol and stroke.

PMID- 18061039
TI  - Chikungunya in Europe: what's next?

PMID- 18061040
TI  - Promise of new Japanese encephalitis vaccines.

PMID- 18061041
TI  - HIV testing: the mutual rights and responsibilities of partners.

PMID- 18061042
TI  - Ten myths and one truth about generalised HIV epidemics.

PMID- 18061043
TI  - Drop of HIV estimate for India to less than half.

PMID- 18061044
TI  - Brominated flame retardants--safety at what cost?

PMID- 18061045
TI  - Elizabeth Mataka: UN Special Envoy for HIV/AIDS in Africa.

PMID- 18061046
TI  - Diaphragms and lubricant gel for prevention of HIV.

PMID- 18061048
TI  - Diaphragms and lubricant gel for prevention of HIV.

PMID- 18061049
TI  - Misoprostol and pregnancy termination.

PMID- 18061050
TI  - Misoprostol and pregnancy termination.

PMID- 18061051
TI  - The JIKEI trial.

PMID- 18061053
TI  - Setting standards for harmonisation.

PMID- 18061054
TI  - Use of pressors in the management of septic shock.

PMID- 18061056
TI  - Use of pressors in the management of septic shock.

PMID- 18061057
TI  - Quality standards in medical education.

PMID- 18061058
TI  - Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta
      analysis of individual data from 61 prospective studies with 55,000 vascular
      deaths.
AB  - BACKGROUND: Age, sex, and blood pressure could modify the associations of total
      cholesterol (and its main two fractions, HDL and LDL cholesterol) with vascular
      mortality. This meta-analysis combined prospective studies of vascular mortality
      that recorded both blood pressure and total cholesterol at baseline, to determine
      the joint relevance of these two risk factors. METHODS: Information was obtained
      from 61 prospective observational studies, mostly in western Europe or North
      America, consisting of almost 900,000 adults without previous disease and with
      baseline measurements of total cholesterol and blood pressure. During nearly 12
      million person years at risk between the ages of 40 and 89 years, there were more
      than 55,000 vascular deaths (34,000 ischaemic heart disease [IHD], 12,000 stroke,
      10,000 other). Information about HDL cholesterol was available for 150,000
      participants, among whom there were 5000 vascular deaths (3000 IHD, 1000 stroke,
      1000 other). Reported associations are with usual cholesterol levels (ie,
      corrected for the regression dilution bias). FINDINGS: 1 mmol/L lower total
      cholesterol was associated with about a half (hazard ratio 0.44 [95% CI 0.42
      0.48]), a third (0.66 [0.65-0.68]), and a sixth (0.83 [0.81-0.85]) lower IHD
      mortality in both sexes at ages 40-49, 50-69, and 70-89 years, respectively,
      throughout the main range of cholesterol in most developed countries, with no
      apparent threshold. The proportional risk reduction decreased with increasing
      blood pressure, since the absolute effects of cholesterol and blood pressure were
      approximately additive. Of various simple indices involving HDL cholesterol, the
      ratio total/HDL cholesterol was the strongest predictor of IHD mortality (40%
      more informative than non-HDL cholesterol and more than twice as informative as
      total cholesterol). Total cholesterol was weakly positively related to ischaemic
      and total stroke mortality in early middle age (40-59 years), but this finding
      could be largely or wholly accounted for by the association of cholesterol with
      blood pressure. Moreover, a positive relation was seen only in middle age and
      only in those with below-average blood pressure; at older ages (70-89 years) and,
      particularly, for those with systolic blood pressure over about 145 mm Hg, total
      cholesterol was negatively related to haemorrhagic and total stroke mortality.
      The results for other vascular mortality were intermediate between those for IHD
      and stroke. INTERPRETATION: Total cholesterol was positively associated with IHD
      mortality in both middle and old age and at all blood pressure levels. The
      absence of an independent positive association of cholesterol with stroke
      mortality, especially at older ages or higher blood pressures, is unexplained,
      and invites further research. Nevertheless, there is conclusive evidence from
      randomised trials that statins substantially reduce not only coronary event rates
      but also total stroke rates in patients with a wide range of ages and blood
      pressures.

PMID- 18061059
TI  - Infection with chikungunya virus in Italy: an outbreak in a temperate region.
AB  - BACKGROUND: Chikungunya virus (CHIKV), which is transmitted by Aedes spp
      mosquitoes, has recently caused several outbreaks on islands in the Indian Ocean
      and on the Indian subcontinent. We report on an outbreak in Italy. METHODS: After
      reports of a large number of cases of febrile illness of unknown origin in two
      contiguous villages in northeastern Italy, an outbreak investigation was done to
      identify the primary source of infection and modes of transmission. An active
      surveillance system was also implemented. The clinical case definition was
      presentation with fever and joint pain. Blood samples were gathered and analysed
      by PCR and serological assays to identify the causal agent. Locally captured
      mosquitoes were also tested by PCR. Phylogenetic analysis of the CHIKV E1 region
      was done. FINDINGS: Analysis of samples from human beings and from mosquitoes
      showed that the outbreak was caused by CHIKV. We identified 205 cases of
      infection with CHIKV between July 4 and Sept 27, 2007. The presumed index case
      was a man from India who developed symptoms while visiting relatives in one of
      the villages. Phylogenetic analysis showed a high similarity between the strains
      found in Italy and those identified during an earlier outbreak on islands in the
      Indian Ocean. The disease was fairly mild in nearly all cases, with only one
      reported death. INTERPRETATION: This outbreak of CHIKV disease in a non-tropical
      area was to some extent unexpected and emphasises the need for preparedness and
      response to emerging infectious threats in the era of globalisation.

PMID- 18061060
TI  - Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese
      encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial.
AB  - BACKGROUND: Japanese encephalitis virus (JEV) is the leading cause of viral
      encephalitis in southeast Asia. Although no treatment is currently available,
      vaccination effectively prevents the disease. In a non-inferiority study, we
      aimed to compare the safety and immunogenicity of a novel, second-generation,
      inactivated candidate vaccine for JEV with a licensed, mouse-brain-derived
      vaccine. METHODS: We included 867 adults in a multicentre, multinational,
      observer-blinded, randomised controlled phase III trial. Study sites were located
      in the USA, Germany, and Austria. Volunteers received either the JEV test vaccine
      intramuscularly on a two-dose schedule (on days 0 and 28; n=430) or the licensed
      vaccine subcutaneously according to its recommended three-dose schedule (on days
      0, 7, and 28; n=437). The primary endpoint was immunogenicity, with respect to
      neutralising JEV-specific antibodies assessed by a plaque-reduction
      neutralisation test, which was assessable in 725 patients in the per-protocol
      population. This trial is registered as a clinical trial, EudraCT number 2004
      002474-36. FINDINGS: The safety profile of the test vaccine was good, and its
      local tolerability profile was more favourable than that of the licensed vaccine.
      Frequency of adverse events was similar between treatment groups, and vaccine
      related adverse events were generally mild. The seroconversion rate of the test
      vaccine was 98% compared with 95% for the licensed vaccine on day 56 (95% CI for
      the difference -1.33 to 3.43). Geometric mean titre for recipients of the test
      vaccine was 244 (range 5-19 783), compared with 102 (5-1864) for the licensed
      vaccine (ratio 2.3 [95% CI 1.967-2.75]). INTERPRETATION: The test JEV vaccine has
      a promising immunogenicity and safety profile.

PMID- 18061061
TI  - A dent in the head.

PMID- 18061062
TI  - Haemochromatosis.
AB  - Since the discovery of the haemochromatosis gene (HFE; chromosome 6p21.3)
      associated with haemochromatosis in 1996, many studies about diverse aspects of
      this common genetic disorder have been done. Some patients present with cirrhosis
      and show high mortality, whereas many asymptomatic homozygotes for the C282Y
      mutation in the haemochromatosis gene identified in population screening studies,
      who have been followed up for many years, do not develop iron overload. Studies
      described the usefulness of transferrin saturation and serum ferritin tests, and
      the acceptability of genetic testing for haemochromatosis. Phlebotomy therapy
      improves hepatic fibrosis. Here, we summarise some new findings in
      haemochromatosis, a disorder first described in 1865.

PMID- 18061063
TI  - Kaleidoscopic vision and a jerking leg on the ski slope.

PMID- 18061065
TI  - Limitation of angiography to identify the culprit plaque in acute myocardial
      infarction with coronary total occlusion utility of coronary plaque temperature
      measurement to identify the culprit plaque.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that the maximal
      temperature (Tmax) site, as measured by thermal wire, coincides with the culprit
      plaque by intravascular ultrasound (IVUS) in patients with acute myocardial
      infarction (AMI). BACKGROUND: Subsequent thrombosis developing to the proximal
      region from the site of plaque rupture or erosion can potentially complicate the
      ability of coronary angiography to identify the accurate culprit plaque in
      patients with coronary total occlusion. METHODS: In 45 consecutive patients with
      a first anterior AMI, the Tmax site by thermal wire and the culprit plaque by
      IVUS were evaluated in the left anterior descending coronary artery (LAD).
      RESULTS: Twenty-five patients had LAD total occlusion, and the remaining 20 had
      LAD reperfusion. In both groups of patients, the Tmax site was significantly more
      distal to the angiographically most stenotic site or occlusive site (reperfusion:
      mean distance [MD] = 1.1 mm distal, 95% confidence interval [CI] 0.3 to 1.9 mm, p
      = 0.01; total occlusion: MD = 8.8 mm distal, 95% CI 8.0 to 9.6 mm, p < 0.0001).
      The culprit plaques by IVUS approximately coincided with those by angiography or
      thermal wire in patients with reperfusion. However, the angiographic occlusive
      site was significantly more proximal to the culprit plaque by IVUS (MD = 9.2 mm,
      95% CI 7.9 to 10.6 mm, p < 0.0001), but the Tmax site coincided with the culprit
      plaque by IVUS (MD = 0.3 mm distal, 95% CI 0.3 mm proximal to 1.0 mm distal, p =
      0.293) in patients with total occlusion. CONCLUSIONS: Temperature measurement of
      coronary plaque enables accurate localization of the culprit plaque in AMI with
      coronary total occlusion.

PMID- 18061066
TI  - Culprit plaque in myocardial infarction going beyond angiography.

PMID- 18061067
TI  - Active Coxsackieviral B infection is associated with disruption of dystrophin in
      endomyocardial tissue of patients who died suddenly of acute myocardial
      infarction.
AB  - OBJECTIVES: In this study, we evaluated the potential direct role of enterovirus
      (EV) cardiac infections in the pathogenesis of myocardial infarction (MI).
      BACKGROUND: Enteroviruses (Picornaviridae) have been suspected to play a role in
      the development of acute MI. METHODS: The presence of EV ribonucleic acid (RNA)
      sequences and capsid viral protein 1 (VP1) and the virus-mediated focal
      disruption of dystrophin were retrospectively investigated by reverse
      transcriptase-polymerase chain reaction and immunohistochemistry assays in
      endomyocardial tissues of patients who died suddenly of acute MI by comparison
      with similar samples of control patients matched for gender, residence area, and
      year of death. RESULTS: Enterovirus infection markers were detected in 20 (40%)
      of 50 patients who died suddenly of MI, 2 (4%) of 50 matched subjects without
      cardiac disease (p < 0.001), and 4 (8%) of 50 matched patients exhibiting a
      noncoronary chronic cardiopathy (p < 0.001). All of the EV RNA-positive patients
      exhibited VP1, which provided evidence of viral protein synthesis activity. The
      VP1 gene sequences amplified after cloning from myocardial or coronary samples of
      8 of the MI patients and showed a strong homology with sequences of
      coxsackievirus B2 and B3 serotypes. Moreover, in the endomyocardial tissue of
      these 8 patients, immunohistochemical analyses demonstrated that there was
      disruption of the sarcolemmal localization of dystrophin in the same tissue areas
      that were infected by coxsackieviruses. CONCLUSIONS: Our findings demonstrate a
      significantly higher proportion of active coxsackievirus B cardiovascular
      infections in patients who suddenly died of MI compared with matched control
      subjects, suggesting that these EVs may significantly contribute to the
      pathogenesis of acute MI by a focal disruption of the dystrophin-glycoprotein
      complex.

PMID- 18061068
TI  - Myocardial infarction, viral infection, and the cytoskeleton final common
      pathways of a common disease?

PMID- 18061069
TI  - Determinants of progression of coronary artery calcification in type 2 diabetes
      role of glycemic control and inflammatory/vascular calcification markers.
AB  - OBJECTIVES: This study prospectively evaluated the relationship between
      cardiovascular risk factors, selected biomarkers (high-sensitivity C-reactive
      protein [hs-CRP], interleukin [IL]-6, and osteoprotegerin [OPG]), and the
      progression of coronary artery calcification (CAC) in type 2 diabetic subjects.
      BACKGROUND: Coronary artery calcification is pathognomonic of coronary
      atherosclerosis. Osteoprotegerin is a signaling molecule involved in bone
      remodeling that has been implicated in the regulation of vascular calcification
      and atherogenesis. METHODS: Three hundred ninety-eight type 2 diabetic subjects
      without prior coronary disease or symptoms (age 52 +/- 8 years, 61% male,
      glycated hemoglobin [HbA(1)c] 8 +/- 1.5) were evaluated serially by CAC imaging
      (mean follow-up 2.5 +/- 0.4 years). Progression/regression of CAC was defined as
      a change > or =2.5 between the square root transformed values of baseline and
      follow-up volumetric CAC scores. Demographic data, risk factors, glycemic
      control, medication use, serum hs-CRP, IL-6, and plasma OPG levels were measured
      at baseline and follow-up. RESULTS: Two hundred eleven patients (53%) had CAC at
      baseline. One hundred eighteen patients (29.6%) had CAC progression, whereas 3
      patients (0.8%) had regression. Age, male gender, hypertension, baseline CAC,
      HbA(1)c >7, waist-hip ratio, IL-6, OPG, use of beta-blockers, calcium channel
      antagonists, angiotensin-converting enzyme (ACE) inhibitors, statins, and
      Framingham/UKPDS (United Kingdom Prospective Diabetes Study) risk scores were
      univariable predictors of CAC progression. In the multivariate model, baseline
      CAC (odds ratio [OR] for CAC >400 = 6.38, 95% confidence interval [CI] 2.63 to
      15.5, p < 0.001), HbA(1)c >7 (OR 1.95, CI 1.08 to 3.52, p = 0.03), and statin use
      (OR 2.27, CI 1.38 to 3.73, p = 0.001) were independent predictors of CAC
      progression. CONCLUSIONS: Baseline CAC severity and suboptimal glycemic control
      are strong risk factors for CAC progression in type 2 diabetic subjects.

PMID- 18061070
TI  - Oxidative inhibition of the mitochondrial aldehyde dehydrogenase promotes
      nitroglycerin tolerance in human blood vessels.
AB  - OBJECTIVES: We tested the hypothesis of whether an inhibition of the
      nitroglycerin (GTN) bioactivating enzyme mitochondrial aldehyde dehydrogenase
      (ALDH-2) contributes to GTN tolerance in human blood vessels. BACKGROUND: The
      hemodynamic effects of GTN are rapidly blunted by the development of tolerance, a
      phenomenon associated with increased formation of reactive oxygen species (ROS).
      Recent studies suggest that ROS-induced inhibition of ALDH-2 accounts for
      tolerance in animal models. METHODS: Segments of surgically removed arteria
      mammaria and vena saphena from patients undergoing coronary bypass surgery were
      used to examine the vascular responsiveness to GTN and the endothelium-dependent
      vasodilator acetylcholine. The ALDH-2 activity and expression in these segments
      were assessed by the conversion of a benzaldehyde or its derivative to the
      benzoic acid metabolite and by Western blotting technique. RESULTS: In contrast
      to patients not treated with nitrates (n = 36), patients treated with GTN for 48
      h (n = 14) before surgery showed tolerance to GTN and endothelial dysfunction in
      arterial and venous vessels. In vivo GTN tolerance was mimicked in vitro by
      incubation of nontolerant vessels with the ALDH-2 inhibitor benomyl. In vivo GTN
      treatment decreased vascular aldehyde dehydrogenase activity compared with
      nontolerant vessels and decreased the expression of ALDH-2 in arterial tissue.
      Incubation of control venous vessels with GTN caused a significant attenuation of
      aldehyde dehydrogenase activity that was reversed by presence of the sulfhydryl
      group donor dithiothreitol. CONCLUSIONS: Long-term GTN treatment induces
      tolerance and endothelial dysfunction in human vessels, associated with an
      inhibition and down-regulation of vascular ALDH-2. Thus, these findings extend
      results of previous animal studies to humans.

PMID- 18061071
TI  - Driving and implantable cardioverter-defibrillator shocks for ventricular
      arrhythmias: results from the TOVA study.
AB  - OBJECTIVES: This study examined the risk of implantable cardioverter
      defibrillator (ICD) shocks for ventricular tachycardia (VT) or ventricular
      fibrillation (VF) associated with driving. BACKGROUND: Concerns regarding VT/VF
      occurring during driving are the basis for driving restrictions in ICD patients;
      however, limited data are available to inform recommendations. METHODS: This
      study used a prospective nested case-crossover design to compare the risk of ICD
      shock for VT/VF both during and up to 60 min after an episode of driving as
      compared with that during other activities among 1,188 ICD patients enrolled in
      the TOVA (Triggers of Ventricular Arrhythmia) study. RESULTS: Over a median
      follow-up of 562 days, there were 193 ICD shocks for VT/VF with data on exposure
      to driving before ICD shock. The absolute risk of ICD shock for VT/VF within 1 h
      of driving was estimated to be 1 episode per 25,116 person-hours spent driving.
      The ICD shocks for VT/VF were twice as likely to occur within 1 h of driving a
      car as compared with other times (relative risk [RR] 2.24, 95% confidence
      interval [CI] 1.57 to 3.18). This risk was specific for shocks for VT/VF and
      occurred primarily during the 30-min period after driving (RR 4.46, 95% CI 2.92
      to 6.82) rather than during the driving episode itself (RR 1.05, 95% CI 0.48 to
      2.30). CONCLUSIONS: Although the risk of ICD shock for VT/VF was transiently
      increased in the 30-min period after driving, the risk was not elevated during
      driving and the absolute risk was low. These data provide reassurance that
      driving by ICD patients should not translate into an important rate of personal
      or public injury.

PMID- 18061072
TI  - Driving and implantable cardioverter-defibrillators a clearer view.

PMID- 18061073
TI  - Circulating progenitor cells can be reliably identified on the basis of aldehyde
      dehydrogenase activity.
AB  - OBJECTIVES: Our objective was to develop and assess a novel endogenous progenitor
      cell (EPC) assay based on aldehyde dehydrogenase (ALDH) activity, and to define
      the relationship of ALDH-bright (ALDH(br)) cells with previously defined EPCs,
      patient age, and extent of coronary artery disease. BACKGROUND: Accurate
      assessment of circulating EPCs is of significant interest, yet current assays
      have limitations. Progenitor cells display high levels of ALDH activity. An assay
      based on ALDH activity may offer a simple means for enumerating EPCs. METHODS: We
      simultaneously determined the numbers of EPCs based on ALDH activity and cell
      surface expression of CD133, CD34, and vascular endothelial growth factor
      receptor-2 in 110 patients undergoing cardiac catheterization. We assessed the
      reproducibility of these estimates, correlation among EPC assays, and the
      association of ALDH(br) numbers with age and disease severity. RESULTS: Aldehyde
      dehydrogenase-bright cells were easily identified in nonmobilized peripheral
      blood with median and mean frequencies of 0.041% and 0.074%, respectively.
      Aldehyde dehydrogenase-bright cells expressed CD34 or CD133 cell surface markers
      (57.0% and 27.1%, respectively), correlated closely with CD133+CD34+ cells (r =
      0.72; p < 0.001), and differentiated into endothelial cells with greater
      efficiency than CD133+CD34+ cells. Aldehyde dehydrogenase-bright cell numbers
      were inversely associated with patient age and coronary disease severity.
      CONCLUSIONS: Aldehyde dehydrogenase activity represents a novel simplified method
      for quantifying EPCs. The correlation of ALDH(br) cells with clinical factors and
      outcomes warrants further study.

PMID- 18061074
TI  - Extracellular superoxide dismutase accelerates endothelial recovery and inhibits
      in-stent restenosis in stented atherosclerotic Watanabe heritable hyperlipidemic
      rabbit aorta.
AB  - OBJECTIVES: This study examined whether local gene therapy with extracellular
      superoxide dismutase (EC-SOD) could inhibit in-stent restenosis in
      atherosclerotic Watanabe heritable hyperlipidemic rabbits. BACKGROUND: Stenting
      causes an acute increase in superoxide anion production and oxidative stress; EC
      SOD is a major component of antioxidative defense in blood vessels and has
      powerful cardioprotective effects in ischemic myocardium. METHODS: Endothelial
      denudation and stenting were done in 36 adult (15 to 18 months old) rabbits.
      Catheter-mediated intramural delivery of clinical good manufacturing practice
      grade adenoviruses encoding rabbit EC-SOD were done simultaneously with stenting.
      Control animals received adenovirus-encoding nuclear-targeted beta-galactosidase
      (AdLacZ). Circulating markers for oxidative stress (nonesterified 8-iso
      prostaglandin F2 alpha) were measured. Analysis of 6-day, 28-day, and 90-day
      vessel histology, radical production, oxidation-specific epitopes, and expression
      studies were performed. RESULTS: The EC-SOD treatment reduced oxidant production
      in stented vessels compared with control vessels. Early systemic recovery of
      total SOD activity was observed in the treated rabbits. The EC-SOD significantly
      accelerated endothelial recovery (67.4% +/- 10.8% vs. 24.2.1% +/- 4.6% at 6 days,
      p < 0.05; 89.3% +/- 3.7% vs. 45.1% +/- 9.6% at 28 days, p < 0.05), and the
      beneficial effect involved increased proliferation of regenerating endothelium.
      The EC-SOD group showed a 61.3% lower (p < 0.05) neointimal formation at 28 days,
      with a similar, albeit nonsignificant trend at 90 days (1.20 +/- 0.32 mm2 vs.
      1.88 +/- 0.24 mm2, p = 0.06). CONCLUSIONS: The results suggest a central
      pathogenetic role of oxidation sensitive signaling processes in endothelial
      recovery and developing in-stent restenosis in atherosclerotic vessels. Local
      therapy against oxidative stress represents a promising therapeutic strategy in
      stent-induced vascular injury.

PMID- 18061075
TI  - The year in epidemiology, health services research, and outcomes research.

PMID- 18061076
TI  - How do I get a paper accepted? Concerns of a junior researcher.

PMID- 18061078
TI  - 2007 chronic angina focused update of the ACC/AHA 2002 guidelines for the
      management of patients with chronic stable angina: a report of the American
      College of Cardiology/American Heart Association Task Force on Practice
      Guidelines Writing Group to develop the focused update of the 2002 guidelines for
      the management of patients with chronic stable angina.

PMID- 18061080
TI  - Prolonged and perplexing fevers in antiquity: malaria and typhoid fever.
AB  - Fever of unknown origin is a topic that has enduring interest to physicians.
      Prolonged fevers of infectious etiology were of particular concern to the ancient
      physician. This overview of prolonged fevers in antiquity focuses on malaria and
      typhoid fever as the primary infectious causes. By studying texts from
      Mesopotamian, Greek, and Roman physicians and observers of disease, it is
      possible to determine the likely etiology of many of these ancient plagues. The
      historical import of these diseases should not be overlooked, and it is for this
      reason that the prolonged fevers of antiquity have profound significance and
      enduring interest.

PMID- 18061081
TI  - Fever of unknown origin: clinical overview of classic and current concepts.
AB  - Fever of unknown origin (FUO) refers to disorders that present with prolonged and
      perplexing fevers that are difficult to diagnose. This article presents a
      clinical overview of classic and current causes of FUOs, which may be due to
      infectious, rheumatic/inflammatory, neoplastic, or miscellaneous disorders.
      Comprehensive but nonfocused diagnostic testing is ineffective and should be
      avoided. The FUO workup should be directed by the key history, physical, and
      laboratory findings in clinical presentation. The clinical syndromic approach in
      the differential diagnosis of FUOs is emphasized, and the diagnostic importance
      and significance of fever patterns are discussed.

PMID- 18061082
TI  - Fever of unknown origin: historical and physical clues to making the diagnosis.
AB  - Fever of unknown origin (FUO) has fascinated and perplexed clinicians for over a
      century. No published guidelines exist on the approach to FUO, and studies have
      demonstrated that a diagnosis is never established in up to 30% of cases. A
      comprehensive history and physical examination are the keys to establishing a
      diagnosis in patient with FUO. This article provides a systematic approach to the
      diagnosis of FUO by delineating the most important elements of a comprehensive
      history and physical examination.

PMID- 18061083
TI  - Fever of unknown origin in older persons.
AB  - Infectious diseases in general in the aged are associated with higher morbidity
      and mortality rates. Decremental biologic changes with age affect host defenses
      and responses to infection, and the frequent presence of comorbidities also may
      adversely impact host defenses, especially in frail older persons. Infections may
      present differently in older persons than in younger populations, making early
      diagnosis difficult. Within this context, the article explores the importance of
      how fever of unknown origin (FUO) in the old differs significantly from FUO in
      younger adults because the etiology is different. Moreover, it is important to
      aggressively determine the etiology of FUO in this older population because it is
      often treatable.

PMID- 18061084
TI  - Fever of unknown origin caused by tuberculosis.
AB  - Tuberculosis is an important cause of fever of unknown origin. Travel, age,
      dialysis, diabetes, birth in a country with a high prevalence of tuberculosis,
      and immunoincompetence are among the most salient risks. Associated physical
      findings, radiologic evaluation, and hematologic and endocrinologic abnormalities
      may provide clues to the diagnosis. Both noninvasive and invasive diagnostic
      modalities are reviewed. Because diagnosis may be elusive, therapeutic and
      diagnostic trials of antituberculous therapy should be considered in all patients
      with fever of unknown origin who defy diagnosis.

PMID- 18061085
TI  - Fever of unknown origin due to zoonoses.
AB  - Fevers of unknown origin have been classified as classic, nosocomial, immune
      deficient, and HIV-related. More than half of the 1407 human pathogens are
      zoonotic, making zoonotic infections an important subcategory in each of the
      classifications. This article describes both common and unusual zoonoses causing
      fevers of unknown origin. Simian immune virus is considered as a possible
      emerging infection. For special populations (the homeless, zoophiliacs, those
      whose occupation or leisure brings them in close contact with oceans or lakes,
      and veterinarians), zoonotic infection potentials are discussed.

PMID- 18061086
TI  - Fever of unknown origin due to rickettsioses.
AB  - Most common rickettsioses do not fill the criteria for fever of unknown origin,
      with fever often inferior to lasting less than 1 week. Q fever, scrub typhus,
      murine typhus, human monocytic ehrlichiosis, and Bartonellosis could fill these
      criteria, however, notably in uncommon presentations. Moreover, in patients
      returning from tropical areas or from geographic endemic areas for rickettsiosis,
      or in patients in contact with animals or ticks, theses etiologies should be kept
      in mind by physicians challenged to diagnose cause of fever. In this context,
      even without confirmation of diagnosis, treatment with doxycycline should be
      used.

PMID- 18061087
TI  - Fever of unknown origin in HIV/AIDS patients.
AB  - Fever of unknown or uncertain origin (FUO) constitutes a common clinical
      challenge in patients infected with HIV. It is usually caused by disseminated
      opportunistic infection, and the relative frequency of each cause of FUO is
      influenced by multiple factors including CD4 count, geographic setting, and local
      prevalences of infectious agents, which may provide clues to the diagnosis.
      Infections presenting as FUO in the HIV population occur most often in the late
      stages of the disease and high diagnostic suspicion for mycobacterial disease
      should be maintained when evaluating these patients, particularly in areas of
      high prevalence. This article discusses the causes, diagnosis, and treatment of
      FUO in HIV-infected individuals.

PMID- 18061088
TI  - Fever of unknown origin in solid organ transplant recipients.
AB  - Fever is a common clinical manifestation in transplant patients, and it may be
      due to many different reasons. In the general population, infections and
      malignancies as causes of fever of unknown origin (FUO) have decreased over time,
      whereas inflammatory diseases and undiagnosed fevers have increased. This article
      reviews FUO in transplant patients, despite there being no clear and widely
      accepted definition of FUO for such patients. The methodology of diagnosis has
      been accelerated and made more accurate, not only for the imaging diagnosis but
      also for microbiology. With respect to diagnosis of FUO in the transplant patient
      population, consideration should be given to the specific type of transplant
      patient, to the results of the physical examination, and to the epidemiological
      antecedents. This article examines an approach that considers different
      syndromes, followed by an etiologically oriented differential diagnosis.

PMID- 18061089
TI  - Fever of unknown origin in febrile leukopenia.
AB  - Febrile neutropenia is a syndrome commonly anticipated in patients receiving
      treatment for cancer. Its management for the last three decades has included the
      prompt administration of empiric antibacterial therapy, which resulted in a
      reduction in mortality. Challenges remain the administration of the most
      appropriate empiric treatment regimen adapted to evolving and changing
      epidemiology of infections in neutropenic patients and resistance rates; the
      development of markers of early diagnosis of severe bacterial or fungal
      infections; the risk stratification of patients; the establishment of targeted
      empiric (preemptive) antifungal therapy criteria; and the containment of
      antimicrobial resistance that compromises effective treatment efforts, through
      effective antibiotic policies and implementation of infection control measures,
      especially hand hygiene. The need for targeted antimicrobial or antifungal
      prophylaxis and supportive strategies like the use of growth factors awaits
      further clarification.

PMID- 18061090
TI  - Fever of unknown origin in the returning traveler.
AB  - The returning traveler with fever presents a diagnostic challenge for the health
      care provider. When evaluating such a patient, the highest priority should be
      given to diseases that are potentially fatal or may represent public health
      threats. A good history is paramount and needs to include destination, time and
      duration of travel, type of activity, onset of fever in relation to travel,
      associated comorbidities, and any associated symptoms. Pretravel immunizations
      and chemoprophylaxis may alter the natural course of disease and should be
      inquired about specifically. The fever pattern, presence of a rash or eschar,
      organomegaly, or neurologic findings are helpful physical findings. Laboratory
      abnormalities are nonspecific but when corroborated with clinical and
      epidemiologic data may offer a clue to diagnosis.

PMID- 18061091
TI  - Fever of unknown origin in rheumatic diseases.
AB  - Noninfectious inflammatory diseases (connective tissue diseases, vasculitis
      syndromes, granulomatous diseases) emerged as the most frequent cause of fever of
      unknown origin in western countries. Among these diseases, giant cell arteritis
      and polymyalgia rheumatica are the most frequent specific diagnosis in the
      elderly and adult-onset Still's disease the most frequent in younger patients.
      This article focuses on noninfectious inflammatory diseases as a cause of classic
      fever of unknown origin (mainly rheumatic diseases, such as vasculitis and
      connective tissue diseases).

PMID- 18061092
TI  - Fever of unknown origin: focused diagnostic approach based on clinical clues from
      the history, physical examination, and laboratory tests.
AB  - The causes of fevers of unknown origin (FUOs) are diverse and may be the result
      of infectious rheumatic or inflammatory, neoplastic, or miscellaneous disorders.
      This article reviews the focused diagnostic approach to FUOs, emphasizing
      relevant history, physical examination, and selected laboratory tests using a
      clinical syndrome approach. Laboratory tests should be guided by the most likely
      diagnoses based on the presenting clinical syndrome. Considered in concert,
      nonspecific laboratory tests may provide important diagnostic clues. Using a
      sequential diagnostic approach, a focused evaluation diagnoses all but the rarest
      or most obscure causes of FUO.

PMID- 18061093
TI  - Recurrent fevers of unknown origin.
AB  - Recurrent fever of unknown origin is mostly caused by rather rare diseases and
      many cases remain unexplained. The very limited literature data do not allow one
      to construct a diagnostic algorithm. A number of general principles should be
      kept in mind before starting the investigation for this rare subtype of fever of
      unknown origin.

PMID- 18061094
TI  - Fever of unknown origin: is there a role for empiric therapy?
AB  - Empiric therapy has little or no role to play in cases of classic fever of
      unknown origin with three important exceptions: cases that meet criteria for
      culture-negative endocarditis; cases in which findings or the clinical setting
      suggests cryptic disseminated tuberculosis (or, occasionally, other granulomatous
      infections); and cases in which temporal arteritis with vision loss is suspected.
      Several studies indicate that patients with prolonged, undiagnosed fever of
      unknown origin generally have a favorable prognosis. A small and largely
      anecdotal literature suggests a small role for symptomatic use of corticosteroids
      or nonsteroidal anti-inflammatory agents in highly selected cases.

PMID- 18061097
TI  - Eosinophilic esophagitis: history, nomenclature, and diagnostic guidelines.
AB  - Previously believed a rare condition, there has been a rising number of cases of
      eosinophilic esophagitis in adult and pediatric populations over the past several
      years. Because of this increase, it is important for clinicians to be able to
      recognize, diagnose, and manage this disease. This article focuses on the history
      and nomenclature of eosinophilic esophagitis and its evolution as a separate
      entity from gastroesophageal reflux disease. It also outlines currently accepted
      diagnostic criteria for this increasingly common condition.

PMID- 18061098
TI  - Eosinophilic esophagitis in children: clinical manifestations.
AB  - During the past decade, the increasing number of recognized cases of eosinophilic
      esophagitis in children and adults has resulted in a dramatic expansion of the
      medical literature surrounding it. Clinical and basic research has contributed to
      a better, but still incomplete, body of knowledge regarding its clinical and
      histologic manifestations, as well as its immunologic and genetic pathogenesis.
      This article provides a broad framework for recognizing the remarkable variety of
      clinical manifestations of eosinophilic esophagitis in children, which must be
      considered as part of the differential diagnosis in many different clinical
      situations.

PMID- 18061099
TI  - Demographic data and symptoms of eosinophilic esophagitis in adults.
AB  - The clinical presentation of eosinophilic esophagitis in adults is varied but
      most often starts with some form of dysphagia. These patients often may be
      diagnosed incorrectly as having gastroesophageal reflux disease or functional
      disease, given the paucity of objective endoscopy and radiographic findings in
      some patients, even though symptoms often are severe and persistent. A careful
      history with attention to detail and a compilation of compatible characteristics
      is key to the clinician's diagnosing eosinophilic esophagitis in an adult.

PMID- 18061100
TI  - Epidemiology and etiology of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EE) is an inflammatory disease of the esophagus
      characterized by eosinophilic infiltration of the esophageal mucosa. Symptoms of
      EE are variable, and include gastroesophageal reflux symptoms, abdominal pain,
      growth failure, and dysphagia. Dysphagia is a more common presentation in adults
      and older children. Serious complications of EE consisting of esophageal food
      impactions necessitating urgent endoscopic removal of the food and esophageal
      strictures requiring endoscopic balloon dilatations are also seen. The potential
      severity of these symptoms points to the importance of proper recognition and
      management of the disease, especially given that EE has become more prevalent
      over the past decade. In this article, available evidence on the epidemiology and
      etiology of EE is discussed.

PMID- 18061101
TI  - Eosinophilic esophagitis: endoscopic findings.
AB  - Eosinophilic esophagitis is a condition characterized by a dense infiltration of
      eosinophils within the epithelium that may extend into the deeper layers of the
      esophagus associated with distinctive endoscopic changes. The changes are
      frequently found in patients who have hypersensitivity to various foods and
      aeroallergens but overlap exists with gastroesophageal reflux disease. It is
      essential for all endoscopists to become familiar with the endoscopic findings of
      eosinophilic esophagitis to avoid delays or errors in diagnosis and to optimally
      assess outcomes of treatment.

PMID- 18061102
TI  - Histopathologic features of eosinophilic esophagitis.
AB  - The pathology of eosinophilic esophagitis (EE) when fully developed in humans is
      highly characteristic and readily discriminated from the histology of the normal
      esophagus. The histologic alterations are not pathognomonic for any of the
      multiple causes of EE, and the correct diagnosis can be made only if the
      histology is correlated with clinical findings. The histology of the normal
      esophagus is reviewed and contrasted with the findings in EE. The characteristic
      findings in EE are illustrated. Selected research in humans and animal models
      pertinent to EE are briefly reviewed.

PMID- 18061103
TI  - Esophageal dysmotility in patients who have eosinophilic esophagitis.
AB  - The understanding of esophageal motility alterations in patients who have
      eosinophilic esophagitis (EE) is in its infancy despite the common presenting
      complaint of dysphagia. A diversity of motility disorders has been reported in
      patients who have EE including achalasia, diffuse esophageal spasm, nutcracker
      esophagus, and nonspecific motility alterations including high-amplitude
      esophageal body contractions, tertiary contractions, abnormalities in lower
      esophageal sphincter pressure, and other peristaltic problems. Some evidence
      suggests that treatment of EE will improve motility. Technological advances such
      as high-resolution manometry and combined manometry with impedance may provide
      new insight into more subtle motility abnormalities.

PMID- 18061104
TI  - Otorhinolaryngologic manifestations of eosinophilic esophagitis.
AB  - Similar to gastrointestinal symptoms of eosinophilic esophagitis (EE), symptoms
      of otorhinolaryngologic disease associated with EE often are refractory to
      traditional treatment of gastroesophageal reflux disease. Patient demographics
      and characteristics often are similar. Clinicians must maintain a high index of
      suspicion to accurately diagnose and manage airway findings related to
      esophagitis. Team collaboration between otolaryngologists, allergists, and
      gastroenterologists will assure the best treatment in this select group of
      predisposed patients.

PMID- 18061105
TI  - The natural history and complications of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis is a chronic disease limited to the esophagus and has a
      persistent or spontaneously fluctuating course. So far it does not seem to limit
      life expectancy, but it often substantially impairs the quality of life. To date,
      there has been no association with malignant conditions, but there is concern
      that the chronic, uncontrolled inflammation will evoke irreversible structural
      alterations of the esophagus, leading to tissue fibrosis, stricture formation,
      and impaired function. This esophageal remodeling may result in several disease
      inherent and procedure-related complications.

PMID- 18061106
TI  - Eosinophilic esophagitis: association with allergic disorders.
AB  - Atopy has been linked to eosinophilic gastrointestinal disorders because of the
      role eosinophils play in atopic disorders. It has also been found that these
      disorders coexist. The goal of this article is to take a step back, and
      considering only eosinophilic esophagitis, attempt to determine from the
      available body of clinical and research literature: (1) Is the coexistence of
      these disorders attributable to a preconceived bias? If so, what is the source of
      the bias and how can it be removed? (2) Is there a cause and effect relationship?
      If so, can this relationship be harnessed for diagnostic and therapeutic
      modalities?

PMID- 18061108
TI  - Translational research on the pathogenesis of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EE) is an inflammatory disease of the esophagus
      characterized by eosinophilic infiltration of the esophageal epithelium. EE is a
      relatively new disease from clinical and research standpoints. A recent surge in
      basic and translational studies has emerged to understand its pathogenesis since
      its recognition as a separate entity from acid-induced gastroesophageal reflux
      disease in 1995. Our understanding of this disease is still limited, however. In
      this article, available evidence from translational studies on EE is discussed,
      focusing on the allergic nature of the disease and highlighting the role of
      various inflammatory cells found in the esophagus of patients who have EE.
      Esophageal remodeling in EE is also discussed.

PMID- 18061107
TI  - Basic pathogenesis of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EE) is a newly recognized disease, which has largely
      been called idiopathic EE, emphasizing the poor understanding of its
      pathogenesis. EE is a severe disease of the esophagus characterized by an
      accumulation of eosinophils in the esophageal mucosa, and is highly associated
      with atopic disease. Nevertheless, the nomenclature "eosinophilic esophagitis"
      describes only the tip of the iceberg of a complex disorder, as the pathogenesis
      of EE involves multiple tissues, cell types, and genes, and derives from complex
      genetic and environmental factors. This article defines the fundamental knowledge
      available to date that characterizes the mechanisms by which certain etiological
      factors cause EE, reviewing human studies, murine models, and recent knowledge
      regarding the involvement of environmental, cellular, molecular, and genetic
      factors in the development of EE.

PMID- 18061109
TI  - Noninvasive markers of eosinophilic esophagitis.
AB  - There has been an increasing awareness and recognition of eosinophilic
      esophagitis (EE), a chronic condition with periods of exacerbation and remission,
      over the last decade. The complex pathophysiology of EE and eosinophil physiology
      provide several candidate biomarkers that could be studied on various
      noninvasively obtained body specimens. This article reviews several potential
      noninvasive biomarkers of EE.

PMID- 18061110
TI  - Pharmacologic treatment of eosinophilic esophagitis.
AB  - There are several treatment options available for patients who have eosinophilic
      esophagitis (EE). These options include dilatation for mechanical esophageal
      abnormalities, pharmacologic therapy, and dietary management. Providing the
      appropriate therapy depends on the significance of clinical symptoms, association
      of abnormal anatomy, and histologic involvement of underlying the esophageal
      tissue. This article focuses on the pharmacotherapy of EE.

PMID- 18061111
TI  - Nutritional management of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis has been increasingly described in pediatric and adult
      literature. Several pediatric studies have indicated that food allergies are
      responsible for more than 90% of pediatric cases. There are three different
      dietary approaches to the management of eosinophilic esophagitis: (1) the
      elemental diet, (2) the removal of foods based on allergy testing, and (3) the
      removal of the foods that most commonly cause eosinophilic esophagitis. This
      article discusses the nutritional risks and benefits of each approach.

PMID- 18061112
TI  - Integrated approach to treatment of children and adults with eosinophilic
      esophagitis.
AB  - Over the last decade, treatment plans for eosinophilic esophagitis included the
      use of elemental formula, elimination diets, systemic corticosteroids, and the
      gavage of aerosolized steroids. Except for one placebo-controlled blinded
      prospective study, most decision making has been based on retrospective or
      uncontrolled studies and clinical experience. In this article, three authors from
      diverse backgrounds combine their resources to propose treatment paths with
      justification based on their clinical experience and interpretation of the
      literature.

PMID- 18061113
TI  - Modified latissimus dorsi and teres major transfer through a single delto
      pectoral approach for external rotation deficit of the shoulder: as an isolated
      procedure or with a reverse arthroplasty.
AB  - Definitive loss of active external rotation of the shoulder impacts an
      individual's ability to perform ADL's, creating severe disability. To restore
      active external rotation, we modified the L'Episcopo procedure by transferring
      both the latissimus dorsi and teres major (LD/TM) through a single delto-pectoral
      approach. The two tendons were rerouted and reattached laterally on the humerus
      to the stump of the pectoralis major which was partially transected to the
      posterior epiphysis. Fifteen consecutive patients who underwent this procedure;
      (mean age 63.2 years), have been followed for at least one year (range 14-63).
      The transfer was indicated alone in 7 patients with an isolated loss of active
      external rotation (ILER) related to an irreparable postero-superior cuff tear. It
      was associated with a reverse shoulder prosthesis in 8 patients with combined
      loss of active elevation and external rotation (CLEER): 6 cases of rotator cuff
      tear arthropathy and 2 of tumor reconstruction. For the series as a whole, the
      mean increase in active elevation was 34.7 degrees . The gain in active external
      rotation was +27 degrees for ILER patients and +28 degrees for CLEER patients.
      Constant score improved to 65.6 (range, 51-79). Subjective shoulder value (SSV)
      was significantly improved from 34% to 72% (P < .0009). All but one patient was
      satisfied or very satisfied with the result. The major contributor to their
      satisfaction was the ability to control the spatial positioning of the arm,
      eliminating the tendency of the forearm to swing in toward the trunk. One patient
      had a return of a lag sign after a fall. The modified tendon transfer, performed
      in the beach chair position through a delto-pectoral approach, is less invasive
      than the classic two-incisions procedure and provides good functional results in
      patients with absent or atrophic infraspinatus and teres minor. When the modified
      LD/TM transfer is associated with a reverse shoulder arthroplasty, it allows to
      restore both active elevation and external rotation.

PMID- 18061114
TI  - Comparison of the subjective shoulder value and the Constant score.
AB  - The purpose of this study was to evaluate the subjective shoulder value (SSV) and
      to compare it with the Constant score (CS). The SSV is defined as a patient's
      subjective shoulder assessment expressed as a percentage of an entirely normal
      shoulder, which would score 100%. Patients who underwent operative treatment for
      rotator cuff repair (n = 247), arthroplasty (n = 83), or stabilization for
      recurrent anterior instability (n = 111) were included in this study. Correlation
      between the SSV and CS was highest postoperatively and was higher in the rotator
      cuff group (0.80) than in the osteoarthritis (0.69) and instability (0.61)
      groups. The relative CS could reliably predict the variance in the SSV in
      patients with rotator cuff tears (54%) and osteoarthritis (41%) and, to a lesser
      extent, in instability patients (23%). The SSV is an easily administered,
      responsive, and valid measure of shoulder function. The SSV may offer an
      improvement over the CS in assessing shoulder instability patients, as the CS may
      overestimate the results of these patients.

PMID- 18061115
TI  - Prevalence of symptoms and signs of shoulder problems in people with diabetes
      mellitus.
AB  - Diabetes mellitus is a known risk factor for frozen shoulder. This study was
      performed to quantify this association and test any relationship with other risk
      factors for diabetic complications. Patients attending diabetic (n = 865) and
      general medical (n = 202) clinics were interviewed and examined. External
      rotation was measured in both shoulders. Glycated hemoglobin A(1c) was measured
      in all diabetic patients. Frozen shoulder was defined as pain for more than 3
      months and external rotation of less than 50% of the unaffected shoulder.
      Bilateral frozen shoulder was defined as external rotation of less than 30
      degrees in both shoulders. Shoulder pain was present in 25.7% of diabetic
      patients compared with 5.0% of general medical patients. The criteria for frozen
      shoulder were fulfilled in 4.3% of diabetic patients and in 0.5% of the general
      medical patients. Only duration of diabetes had a positive association. The
      prevalence of painful or stiff shoulder was greater in diabetic patients than
      general medical patients. The prevalence of frozen shoulder is less than
      previously reported but still greater in diabetic patients.

PMID- 18061116
TI  - Functional outcome of arthroscopic rotator cuff repairs: a correlation of
      anatomic and clinical results.
AB  - Even though several studies have revealed excellent clinical results with
      arthroscopic repair of rotator cuff tendons, poor healing of the repair and
      retearing of the tendon occur in many cases. Patterns of outcome correlating
      functional capacity and anatomic integrity of the repaired rotator cuff are not
      well defined. The goal of this prospective study was to determine the pattern of
      anatomic and functional outcomes among patients undergoing single-row
      arthroscopic rotator cuff repair. This study confirmed that single-row
      arthroscopic repair of small- and medium-sized supraspinatus tendon tears
      significantly improves rotator cuff integrity and functional outcomes. A
      completely healed tendon was observed in 60% of the cases. Age is a predictor of
      cuff integrity after the operation. Functional improvement was greater and
      significant in patients with complete healing at follow-up; however, a recurrent
      tear did not preclude positive functional results.

PMID- 18061117
TI  - Quantification of a glenoid defect with three-dimensional computed tomography and
      magnetic resonance imaging: a cadaveric study.
AB  - Bone loss of the glenoid is a common finding in anterior glenohumeral
      instability. Several methods to measure the size of a glenoid defect have been
      described but have not been validated. In this study, 14 cadaver glenoids with a
      randomly created anteroinferior glenoid defect were used for validation of the so
      called circle method. Measurements were done by 2 researchers on digital
      photographs, 3-dimensional (3D) computed tomography (CT) scans, and magnetic
      resonance images (MRI). The correlation coefficient (r(2)) for comparing
      measurements from the digital photographs with the CT scans was 0.97 for
      researcher 1 and 0.90 for researcher 2. When they compared digital images with
      MRI, the r(2) was 0.93 for researcher 1 and 0.92 for researcher 2. No statistical
      differences were found between the 2 researchers. The circle method is a simple
      method for preoperative quantification of a glenoid defect. Measurements can be
      done with 3D CT scans as well as MRI.

PMID- 18061118
TI  - Glenoid resurfacing: what are the limits to asymmetric reaming for posterior
      erosion?
AB  - Eccentric posterior glenoid erosion is a common condition in osteoarthritis. No
      limits have ever been placed on the degree of eccentric erosion that can be
      corrected while still maintaining sufficient bone stock to implant a glenoid
      securely. Five cadaveric scapulae were dissected. Posterior glenoid erosion was
      created to simulate retroversion of 15 degrees or more. A computed tomography
      (CT) scan confirmed the degree of glenoid retroversion. The glenoid was then
      reshaped to correct the glenoid retroversion to neutral, and a glenoid component
      with central and peripheral pegs was inserted. A second CT scan confirmed the
      correction to neutral and also evaluated the fit of the component into the
      glenoid. In all 5 experimental cases, at least 1 of the 4 pegs penetrated the
      glenoid vault. In 1 case, there was a fracture of the anterior rim. Glenoid
      retroversion of 15 degrees or more cannot be satisfactorily corrected simply by
      reaming to lower the anterior edge of the glenoid and restore neutral version
      when using a glenoid component with peripheral pegs.

PMID- 18061119
TI  - Biomechanical properties of triceps brachii tendon after in vitro simulation of
      different posterior surgical approaches.
AB  - Total elbow arthroplasty is usually performed through a triceps-reflecting or 
      preserving approach. Weakness of extension is common. The purpose of this study
      was to compare the in vitro mechanical properties of the triceps tendon after
      simulation of 3 common exposures. After simulation of the approach and repair,
      cadaveric specimens were mounted on a material testing system and a constant
      velocity elongation was applied. The contralateral elbow served as the control.
      All approaches resulted in a marked weakening of the triceps; however, the Bryan
      Morrey lateral triceps-reflecting technique provided statistically better
      strength than V-Y or longitudinal splitting.

PMID- 18061121
TI  - Dynamic contrast enhanced MRI of mouse fibrosarcoma using small-molecular and
      novel macromolecular contrast agents.
AB  - The aim of the study was a comparison of 2 novel macromolecular contrast agents,
      Gadomer-17 and Polylysine-Gd-DTPA, with commercially available Gd-DTPA in
      determining the quality of tumor microvasculature by dynamic contrast enhanced
      MRI. Three groups of 5 mice with SA-1 tumors were studied. To each group of
      animals one contrast agent was administered; i.e. the first group got Gd-DTPA,
      the second group Gadomer-17 and the third group Polylysine-Gd-DTPA. To perform
      dynamic contrast enhanced MRI a standard keyhole approach was used by which
      consecutive signal intensity change due to contrast agent accumulation in the
      tumor was measured. From the obtained data, tissue permeability surface area
      product PS and fractional blood volume BV were calculated on a pixel-by-pixel
      basis. PS and BV values were calculated for each contrast agent. Based on the
      values, contrast agents were classified according to their performance in
      characterizing tumor microvasculature. Results of our study suggest that Gadomer
      17 and Polylysine-Gd-DTPA are significantly superior to Gd-DTPA in characterizing
      tumor microvasculature.

PMID- 18061122
TI  - Beyond angiogenesis: the role of endothelium in the bone marrow vascular niche.
AB  - Specific tissue microenvironments, or niches, are critical for homing and
      maintenance of both stem cells and tumor cells in vivo. Little is known, however,
      about the molecular interactions between individual cells within these
      microenvironments. Recent studies that describe a newly identified hematopoietic
      stem and tumor cell vascular niche in the bone marrow (BM) suggest a critical
      role for vascular endothelial cell signaling and raise the possibility that
      bidirectional interactions of these cells with the vasculature regulate the niche
      dynamically. The mechanisms that govern hematopoietic stem cell (HSC)/tumor cell
      cross-talk with endothelial cells provide a promising new direction for future
      studies. Here we review recent advances that open new avenues of study in this
      field.

PMID- 18061124
TI  - Ischemic preconditioning modulates mitochondrial respiration, irrespective of the
      employed signal transduction pathway.
AB  - We tested in the in vivo rat heart the hypothesis that although ischemic
      preconditioning can employ different signal transduction pathways, these pathways
      converge ultimately at the level of the mitochondrial respiratory chain. Infarct
      size produced by a 60-min coronary artery occlusion (69%+/-2% of the area at
      risk) was limited by a preceding 15-min coronary occlusion (48%+/-4%).
      Cardioprotection by this stimulus was triggered by adenosine receptor
      stimulation, which was followed by protein kinase C and tyrosine kinase
      activation and then mitochondrial K(+)(ATP)-channel opening. In contrast,
      cardioprotection by 3 cycles of 3-min coronary occlusions (infarct size 27%+/-5%
      of the area at risk) involved the release of reactive oxygen species, which was
      followed by protein kinase C and tyrosine kinase activation, but was independent
      of adenosine receptor stimulation and K(+)(ATP)-channel activation. However, both
      pathways decreased respiratory control index (RCI; state-3/state-2, using
      succinate as complex-II substrate) from 3.1+/-0.2 in mitochondria from sham
      treated hearts to 2.4+/-0.2 and 2.5+/-0.1 in hearts subjected to a single 15-min
      and triple 3-min coronary occlusions, respectively (both P<0.05). The decreases
      in RCI were due to an increase in state-2 respiration, whereas state-3
      respiration was unchanged. Abolition of cardioprotection by blockade of either
      signal transduction pathway was paralleled by a concomitant abolition of
      mitochondrial uncoupling. These observations are consistent with the concept that
      mild mitochondrial uncoupling contributes to infarct size limitation by various
      ischemic preconditioning stimuli, despite using different signal transduction
      pathways. In conclusion, in the in vivo rat heart, different ischemic
      preconditioning (IPC) stimuli can activate highly different signal transduction
      pathways, which seem to converge at the level of the mitochondria where they
      increase state-2 respiration.

PMID- 18061123
TI  - Translational approaches to addressing complex genetic pathways in colorectal
      cancer.
AB  - Colorectal cancer (CRC) is among the most prevalent cancers worldwide and
      represents a major public health challenge in the developed world. From the
      perspective of translational investigation, scientists have enormous opportunity
      to elucidate the molecular genetic mechanisms that contribute to CRC pathogenesis
      because most cancers develop from adenomatous precursor lesions. The process of
      adenoma growth and transformation is accompanied by cumulative mutations in
      dominant genetic pathways that confer a growth advantage. Although this
      developmental process permits interrogation of informative pathways before the
      development of cancer, only a few adenomas progress to CRC. Accordingly, a major
      challenge for clinical translational investigators is to identify the molecular
      signatures that indicate increased likelihood for adenoma progression. By
      corollary, these molecular signatures include mutations in high penetrance
      alleles, which include the Adenomatous Polyposis Coli (APC) gene as well as other
      alleles in the Wnt/beta-catenin signaling pathway that specify increased genetic
      susceptibility to CRC. Interactions between these high penetrance alleles and
      other modifier genes as well as with environmental factors are of particular
      importance to understand the complex network of events that lead to CRC. This
      brief review will highlight 3 areas where important questions concerning genetic
      and environmental risk factors have fueled translational investigation into
      possible pathways that lead to CRC.

PMID- 18061125
TI  - Lovastatin inhibits oxidized low-density lipoprotein-induced plasminogen
      activator inhibitor and transforming growth factor-beta1 expression via a
      decrease in Ras/extracellular signal-regulated kinase activity in mesangial
      cells.
AB  - Oxidized low-density lipoprotein (Ox-LDL) might be involved in the progression of
      renal disease. Ox-LDL stimulation of plasminogen activator inhibitor-1 (PAI-1)
      expression via transforming growth factor-beta (TGF-beta)/Smad signaling in
      mesangial cells required activation of extracellular signal-regulated kinase
      (ERK). Mevalonate depletion by 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase
      inhibitors, or statins, decreases the levels of farnesyl pyrophosphate (FPP) for
      isoprenylation of Ras. We postulate that statins may ameliorate the Ox-LDL
      induced mesangial matrix accumulation by inhibiting Ras/ERK activation with
      subsequent downregulation of TGF-beta target genes. Quiescent mesangial cells
      were incubated for 18 h with and without the presence of lovastatin before 50
      microg/mL of Ox-LDL treatment for 1 h. Lovastatin inhibited markedly the
      stimulatory effects of Ox-LDL on ERK1/2 activation, nuclear Smad3 expression, TGF
      beta1 and PAI-1 mRNA and protein expression, and PAI-1 luciferase activity. These
      inhibitory effects of lovastatin were reversed almost completely by mevalonate or
      FPP. Similar to lovastatin, FTI-277, which is an inhibitor of Ras farnesylation,
      decreased the Ox-LDL-induced activation of ERK/Smad3 and induction of TGF
      beta1/PAI-1. These results indicate that lovastatin prevents the Ox-LDL-induced
      Ras/ERK activation that results in inhibition of Smad3 activation in mesangial
      cells with subsequent downregulation of TGF-beta target genes. Thus, statins seem
      to have antifibrotic effects through their anti-TGF-beta response that are
      relevant in the treatment of chronic renal disease with dyslipidemia.

PMID- 18061126
TI  - Comparative toxicity and cell-tissue distribution study on nanoparticular iron
      complexes using avian embryos and HepG2-cells.
AB  - In this study the toxicity and intracellular availability of iron from iron
      dextran (FeD), iron sucrose (FeS), and iron gluconate (FeG) was compared in
      organs of avian (turkey) embryos and in isolated cells (HepG2) in cell culture.
      Iron uptake was more pronounced in embryonic liver than in renal tissue. Cellular
      iron uptake in liver and kidney was more or less similar for the different
      compounds. Only some experiments showed slightly greater iron concentrations in
      liver and kidney with FeG compared with FeD and FeS. Significant differences were
      found in the survival ratios of the eggs and the embryo weights depending on the
      type of iron complex administered. The rank order of toxicities was FeG>FeS>FeD.
      Iron accumulation in HepG2-cells was extremely high with FeS and FeG, whereas FeD
      did not lead to a relevant iron uptake by HepG2 cells. The excessively high iron
      content of the cells is an in vitro phenomenon found neither in the in ovo model
      with the turkey embryos nor in the clinical use of the compounds. The rank order
      of toxicities in HepG2 cells was FeS>FeG>FeD. Iron uptake in cell culture does
      not reflect the in vivo situation. The in ovo model is more suitable to assess
      the cellular iron uptake and iron toxicity in cells and tissues than the in vitro
      model. In both in ovo and in vitro experiments, FeD seemed to be superior in
      terms of toxicity.

PMID- 18061127
TI  - Exhaled pH, exhaled nitric oxide, and induced sputum cellularity in obese
      patients with obstructive sleep apnea syndrome.
AB  - Airway inflammation plays an important role in obstructive sleep apnea syndrome
      as well as in obesity. Increasingly, researchers are studying airway inflammation
      noninvasively and are studying the new markers of airways inflammation. The aim
      of this study was to measure pH in the exhaled breath condensate (EBC), the
      exhaled nitric oxide (NO), and the inflammatory cell profile in the induced
      sputum of obese patients with and without obstructive sleep apnea syndrome
      (OSAS). The pH in EBC, the exhaled NO, and the induced sputum cells were measured
      in 30 obese patients with OSAS (OOs), in 20 obese patients without OSAS (ONOs),
      and in 10 healthy patients (HPs). Levels of pH in EBC were lower in OOs and in
      ONOs than in HPs. Furthermore, the concentrations of exhaled NO and the
      percentages of neutrophils in the induced sputum were greater in OOs and in ONOs
      than in HPs. No significant differences were found between OO and ONO for other
      measurements of airway inflammation. This study shows the presence of airway's
      inflammation in obese patients with and without OSAS and indicates that the
      "exhaled acidopnea" as well as exhaled NO and sputum neutrophils are good tools
      to measure airway inflammation in these subjects.

PMID- 18061128
TI  - Longitudinal urinary creatinine excretion values among preadolescents and
      adolescents.
AB  - To present longitudinal urinary creatinine excretion data for developmentally
      normal children 9-17 years of age. Only extremely limited data have been
      presented of a longitudinal nature for this age group. Overall, 507 children who
      participated in a prospective, randomized, controlled trial of dental materials
      safety were followed longitudinally for 7 years with renal measures, including
      creatinine excretion. Urinary creatinine means, confidence intervals, and 10th,
      50th, and 90th percentiles are presented by year of age for the entire group, by
      sex, and by race (whites, blacks). Urinary creatinine excretion increases with
      age for both sexes and for both races (P<0.0001). No significant sexual
      difference were observed, although a race difference occurs, with blacks showing
      higher excretion levels than whites (P=0.0003). We present longitudinal urinary
      creatinine excretion data for ages 9-17 in which creatinine excretion increases
      with age throughout the time period. No sexual differences are observed, although
      blacks excrete significantly higher levels of urinary creatinine than do whites.

PMID- 18061129
TI  - ERPs reveal comparable syntactic sentence processing in native and non-native
      readers of English.
AB  - L2 syntactic processing has been primarily investigated in the context of
      syntactic anomaly detection, but only sparsely with syntactic ambiguity. In the
      field of event-related potentials (ERPs) syntactic anomaly detection and
      syntactic ambiguity resolution is linked to the P600. The current ERP experiment
      examined L2 syntactic processing in highly proficient L1 Spanish-L2 English
      readers who had acquired English informally around the age of 5 years. Temporary
      syntactic ambiguity (induced by verb subcategorization information) was tested as
      a language-specific phenomenon of L2, while syntactic anomaly resulted from
      phrase structure constraints that are similar in L1 and L2. Participants judged
      whether a sentence was syntactically acceptable or not. Native readers of English
      showed a P600 in the temporary syntactically ambiguous and syntactically
      anomalous sentences. A comparable picture emerged in the non-native readers of
      English. Both critical syntactic conditions elicited a P600, however, the
      distribution and latency of the P600 varied in the syntactic anomaly condition.
      The results clearly show that early acquisition of L2 syntactic knowledge leads
      to comparable online sensitivity towards temporal syntactic ambiguity and
      syntactic anomaly in early and highly proficient non-native readers of English
      and native readers of English.

PMID- 18061130
TI  - The small subunit (SSU) ribosomal (r) RNA gene as a genetic marker for
      identifying infective 3rd juvenile stage Angiostrongylus cantonensis.
AB  - We have developed a molecular method using PCR-direct sequencing to identify the
      infective 3rd juvenile stage of Angiostrongylus cantonensis, a nematode parasite
      of rodents that can accidentally infect humans and cause eosinophilic meningitis.
      We demonstrate that the 5' end of the small subunit (SSU) ribosomal (r) RNA gene
      is a suitable marker to identify A. cantonensis and distinguish it from other
      closely related Angiostrongylus species. When the SSU rRNA marker was employed on
      nematode populations extracted from the black slug Laevicaulis altae collected in
      2 test sites in the Philippines, the infective 3rd juvenile stage A. cantonensis
      was detected without difficulty. The phylogenetic position of other non
      angiostrongylid nematodes isolated was also determined. The molecular technique
      developed in this study provides a rapid and accurate method for the
      identification of A. cantonensis when morphological identification proves
      difficult or inadequate.

PMID- 18061131
TI  - Amoxicillin pharmacokinetics in pregnant women with preterm premature rupture of
      the membranes.
AB  - OBJECTIVE: This study was undertaken to study the pharmacokinetics of
      intravenously administered amoxicillin in pregnant women with preterm premature
      rupture of the membranes (PPROM). STUDY DESIGN: Healthy women with PPROM were
      recruited and treated with amoxicillin (2 g initially and 1 g subsequently).
      Blood samples were obtained from the opposite arm and concentrations determined
      with the use of high-pressure liquid chromatography. Nonlinear mixed-effects
      modeling was performed in nonlinear mixed effect (population) modeling. RESULTS:
      The pharmacokinetics of 17 patients was described by a 3-compartment model.
      Clearance and volume of distribution at steady state were 22.8 L/h and 21.4 L/h,
      respectively, similar to values in nonpregnant individuals. There was little
      variability between patients. No relationship was observed between values of
      individual pharmacokinetic parameters and various covariates. CONCLUSION: The
      pharmacokinetics of amoxicillin in pregnant patients with PPROM similar to
      nonpregnant individuals. Given the small interindividual variability in
      pharmacokinetics, no dose adjustments are required to account for differences
      between subjects under normal circumstances.

PMID- 18061132
TI  - Phenotype analysis of patients with the risk variant LOC387715 (A69S) in age
      related macular degeneration.
AB  - PURPOSE: To examine phenotypes of age-related macular degeneration (AMD) patients
      with the LOC387715 variant (T allele at rs10490924, A69S). DESIGN: Retrospective,
      observational case series. METHODS: This clinic-based case series data set
      contained 775 unrelated cases of AMD. AMD phenotypes of three groups, determined
      by the number of LOC387715 risk alleles, were compared regarding the presence or
      absence of 16 phenotypic features. RESULTS: The number of AMD cases in each group
      was 164 cases (two risk alleles), 330 cases (one risk allele), and 281 cases
      (zero risk allele). The mean age at examination for homozygous carriers of the
      LOC387715 risk allele was significantly lower (73.9 years) than the age for
      carriers of one (76.4 years) or no (77.1 years) risk allele (P = .0003). Of the
      16 features analyzed, only AMD grade (P = .00002) was significantly associated
      with the LOC387715 variant. As the number of LOC387715 risk alleles increased,
      the proportion of grade 5 AMD cases increased in a dose-response fashion.
      CONCLUSIONS: The LOC387715 variant appears to be an independent risk factor for
      grade 5 (neovascular) AMD. This variant may also be associated with an earlier
      onset of AMD. Phenotypes that suggest a high-risk genotype may prove valuable for
      diagnostic, therapeutic, and research purposes.

PMID- 18061133
TI  - Femtosecond laser shaped penetrating keratoplasty: one-year results utilizing a
      top-hat configuration.
AB  - PURPOSE: To evaluate use of a femtosecond laser to create shaped corneal grafts
      in penetrating keratoplasty (PK) in treatment of corneal disease. DESIGN:
      Prospective, nonrandomized clinical study. METHODS: Six eyes of six patients were
      treated in this initial series. Two had herpetic scarring, two had pseudophakic
      bullous keratopathy, one had Fuchs endothelial dystrophy and one had endothelial
      dystrophy with a corneal scar. Preoperative best spectacle-corrected visual
      acuity (BSCVA) ranged from count fingers to 20/50. Donor and recipient corneas
      were cut in a "top-hat" shaped configuration utilizing a 15-kHz femtosecond
      laser. RESULTS: All eyes were successfully treated without intraoperative
      complications. Mean time to complete suture removal was 7.0 +/- 1.9 months
      (range, 4.1 to 9.7 months). At the one-year postoperative exam, mean endothelial
      cell density was 2030 +/- 600 cells/mm(2) (range, 1007 to 2497 cells/mm(2)),
      which was comparable with cell density measured in a prior series of traditional
      PKs (P = .21). BSCVA ranged from 20/400 to 20/25. In two eyes, preexisting
      retinal conditions limited visual improvement following transplantation.
      CONCLUSIONS: Use of the femtosecond laser allowed precise dissection of donor and
      recipient corneas even when significant opacities were present. The use of a top
      hat configuration allowed for an increased area of wound healing in these eyes.

PMID- 18061134
TI  - Management of canalicular lacerations: epidemiological aspects and experience
      with Mini-Monoka monocanalicular stent.
AB  - PURPOSE: To report the epidemiological data, clinical profile, and surgical
      outcome of canalicular lacerations in an Indian population. DESIGN: Retrospective
      interventional case series. METHODS: All patients who underwent canalicular
      laceration repair from July 1, 2002 to June 30, 2005 at a tertiary eye care
      center were retrospectively reviewed. Demographics, cause of eyelid injury,
      associated ocular injury, surgical management with Mini-Monoka monocanalicular
      stent, and its outcome were analyzed. RESULTS: Sixty-six patients underwent
      eyelid laceration repair, of which 24 (36%) had involvement of the canalicular
      system. The mean age at presentation was 16 years (range, 10 months to 52 years);
      20 (83.3%) patients were males. Mode of injury included the blouse-hook fastener
      in five (20.8%) breast-feeding infants, bicycle handle injury in four (16.7%)
      children, and metal rod injury in five (20.8%) adults. Lower canaliculus was
      involved in 13 (54.1%), upper in eight (33.3%), and both in three (12.5%)
      patients. Simultaneous globe injury was noted in six (25%) patients, five (83.3%)
      of which had upper canalicular involvement. Twenty-seven canalicular lacerations
      (24 patients) underwent stenting with the Mini-Monoka monocanalicular stent.
      Three (11.1%) stents extruded within one month. At the final follow-up (mean,
      18.5 months), canalicular block was noted in two (10%) out of 20 patients; none
      had epiphora. CONCLUSION: Canalicular involvement occurs in 36% of eyelid
      injuries. Injury by the "blouse-hook fastener" is unique to infants in the Indian
      context. Simultaneous globe injury is present in 25% of cases, especially when
      the upper canaliculus is involved. Mini-Monoka stent extrusions occur within one
      month. With an 11.1% extrusion rate, Mini-Monoka stents achieved good anatomical
      (90%) and functional (100%) success in the management of canalicular injury.

PMID- 18061135
TI  - Immunologic markers as potential predictors of systemic autoimmune disease in
      patients with idiopathic scleritis.
AB  - PURPOSE: To determine the clinical value of serological testing in patients with
      idiopathic scleritis. DESIGN: Retrospective case series. METHODS: Medical records
      of patients with scleritis seen at an institutional referral center over an 11
      year period were reviewed. RESULTS: Of 119 patients with scleritis seen at the
      University of Illinois Uveitis Clinic, 91 (76.5%) patients had no known etiology
      at initial presentation. Seventy of the 91 patients were tested for rheumatoid
      factor (RF), 19 (27.1%) of whom had a positive result. Ten (52.6%) of these RF
      positive patients were subsequently diagnosed with rheumatoid arthritis (RA)
      during a mean follow-up of 10.6 months (range, zero to 72 months), whereas only
      one of 51 (2.0%) RF negative patients developed RA, producing an odds ratio for
      developing RA in RF positive patients of 55.6 (95% confidence interval (CI) 7.8
      to 369.8, P=.00001). Of the 70 patients who were tested for anti-neutrophil
      cytoplasmic antibody (ANCA), seven (10.0%) tested positive. Three (42.9%) of the
      ANCA positive patients subsequently developed Wegener granulomatosis (WG),
      whereas only two of 63 ANCA negative patients (3.2%) developed WG during a mean
      follow-up of 8.4 months (range, zero to 72 months). The odds ratio for developing
      WG in patients with idiopathic scleritis and a positive ANCA screen compared with
      a negative ANCA was 22.9 (95% CI 3.4 to 154.2, P=.006). CONCLUSIONS: The
      likelihood of patients with idiopathic scleritis developing RA and WG was
      increased if they had a positive RF or ANCA, supporting the role of immunologic
      marker testing in patients who present without systemic disease.

PMID- 18061136
TI  - En face optical coherence tomography of the posterior pole in high myopia.
AB  - PURPOSE: To evaluate a large series of patients affected by high myopia using
      multiplanar imaging provided by en face optical coherence tomography (OCT).
      DESIGN: Observational cross-sectional study. METHODS: En face OCT longitudinal
      cross-sectional B scans and coronal C scans were obtained in 200 eyes of 100
      patients with myopia greater than -6 diopters and evidence of posterior
      staphyloma at fundus examination and at ultrasound B-scan evaluation. RESULTS: A
      macular hole was present in three eyes (1.5%). We detected posterior retinal
      detachment in 37 cases (18.5%). In 15 eyes (7.5%) detachment was associated with
      a macular hole. In the remaining 22 eyes (11%), the detachment was located in the
      area of the staphyloma, and was associated with vitreoretinal traction in four
      eyes (18.2%) of 22 eyes. There was evidence of detachment of the internal
      limiting membrane (ILM) in 12 eyes (6%) and retinoschisis in 27 (13.5%) of 200
      eyes. Retinal vascular microfolds were detected in 40 eyes (20%), and occurred in
      all cases of peripapillary retinal detachment, ILM detachment, and retinoschisis.
      Paravascular microcysts occurred in three eyes (1.5%), and peripapillary
      detachment of the pigment epithelium in 10 eyes (5%). CONCLUSIONS: En face OCT
      provides accurate imaging of retinal abnormalities in high myopia and allows
      width measurement and point-to-point localization of alterations. Thus, it can
      represent a noninvasive way to detect minimal changes during follow-up. Posterior
      detachment in the absence of a macular hole seems to be related to vitreoretinal
      traction, staphyloma, and inward forces exerted by rigid retinal vessels and ILM.
      En face OCT-assisted surgery of macular holes could help to plan removal of
      premacular tractional structures.

PMID- 18061137
TI  - Preliminary clinical results of Descemet membrane endothelial keratoplasty.
AB  - PURPOSE: To describe the preliminary clinical results of selective
      transplantation of organ cultured, donor Descemet membrane (DM) carrying
      autologous corneal endothelium through a 3.5-mm incision, tentatively named
      Descemet membrane endothelial keratoplasty (DMEK), for the management of corneal
      endothelial disorders. DESIGN: Nonrandomized clinical study. METHODS: In 10
      patients with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy,
      DMEK was performed. A 3.5-mm clear corneal tunnel incision was made, the anterior
      chamber was filled with air, and DM was stripped off from the posterior stroma. A
      9.0-mm diameter DM roll was harvested from an organ cultured donor corneo-scleral
      rim, and inserted into a recipient anterior chamber. The donor tissue was gently
      unfolded, positioned onto the posterior stroma, and secured by completely filling
      the anterior chamber with air for 30 minutes. RESULTS: At one month, six eyes had
      a best-corrected visual acuity of 0.5 (20/40) or better, and three eyes reached
      1.0 (20/20). At six months, the endothelial cell density averaged 2030 (+/-373)
      cells/mm(2) (n = 7). Three eyes showed a complete detachment of the donor tissue
      in the early postoperative course that was managed by removal of the transplant
      and a secondary Descemet stripping endothelial keratoplasty procedure.
      CONCLUSION: DMEK may have potential to become the most preferable technique to
      manage corneal endothelial disorders, because it provides quick and nearly
      complete visual rehabilitation. Because the donor tissue required can be prepared
      from organ cultured corneo-scleral rims, the procedure may be readily accessible
      to most corneal surgeons.

PMID- 18061138
TI  - Diagnosis of ocular toxocariasis by establishing intraocular antibody production.
AB  - PURPOSE: To investigate the role of Toxocara canis in posterior uveitis of
      undetermined origin. DESIGN: Retrospective case-study. METHODS: Paired ocular
      fluid (47 aqueous humor [AH] and two vitreous fluids) and serum samples of 37
      adults and 12 children with undetermined posterior uveitis were retrospectively
      analyzed for intraocular IgG antibody production against Toxocara canis by enzyme
      linked immunosorbent assay and Goldmann-Witmer coefficient (GWC) determination.
      Previous diagnostic investigation by polymerase chain reaction and GWC for Herpes
      simplex virus, Varicella zoster virus, and Toxoplasma gondii had not provided a
      cause of the posterior uveitis. RESULTS: Three of 12 (25%) children showed
      intraocular IgG production against Toxocara canis. One child had vitritis, one
      presented with a low-grade uveitis and a peripheral retinal lesion, and the third
      had posterior uveitis and a chorioretinal scar. All three children had AH IgG
      titers exceeding those of the corresponding serum. In fact, two children had low
      Toxocara serum IgG titers (<1:32) and would have been considered seronegative
      upon routine serology screening. Intraocular antibody production against Toxocara
      canis was absent in all 37 adults, including five seropositive patients.
      CONCLUSIONS: Our results indicate that ocular toxocariasis is mainly a pediatric
      disease. Serological screening is not informative for the diagnosis of
      intraocular Toxocara infection. Toxocara GWC analysis, however, can be of value
      when diagnosing patients with posterior focal lesions or vitritis of unknown
      etiology.

PMID- 18061139
TI  - Medical device development: the challenge for ergonomics.
AB  - High quality, well-designed medical devices are necessary to provide safe and
      effective clinical care for patients as well as to ensure the health and safety
      of professional and lay device users. Capturing the user requirements of users
      and incorporating these into design is an essential component of this. The field
      of ergonomics has an opportunity to assist, not only with this area, but also to
      encourage a more general consideration of the user during medical device
      development. A review of the literature on methods for assessing user
      requirements in engineering and ergonomics found that little published work
      exists on the ergonomic aspects of medical device development. In particular
      there is little advice available to developers on which issues to consider during
      design and development or recommendations for good practice in terms of the
      methods and approaches needed to capture the full range of user requirements. The
      Multidisciplinary Assessment of Technology Centre for Health care (MATCH) is a
      research collaboration that is working in conjunction with industrial
      collaborators to apply ergonomics methods to real case study projects with the
      ultimate aim of producing an industry-focused guide to applying ergonomics
      principles in medical device development.

PMID- 18061140
TI  - Cholesterol and anionic phospholipids increase the binding of amyloidogenic
      transthyretin to lipid membranes.
AB  - Deposition of transthyretin (TTR) amyloid is a pathological hallmark of familial
      amyloidotic polyneuropathy (FAP). Recently we showed that TTR binds to membrane
      lipids via electrostatic interactions and that membrane binding is correlated
      with the cytotoxicity induced by amyloidogenic TTR. In the present study, we
      examined the role of lipid composition in membrane binding of TTR by a surface
      plasmon resonance (SPR) approach. TTR bound to lipid bilayers through both high-
      and low-affinity interactions. Increasing the mole fraction of cholesterol in the
      bilayer led to an increase in the amount of high-affinity binding of an
      amyloidogenic mutant (L55P) TTR. In addition, a greater amount of L55P TTR bound
      with high affinity to membranes made from anionic phospholipids,
      phosphatidylglycerol (PG) and phosphatidylserine (PS), than to membranes made
      from zwitterionic phospholipid phosphatidylcholine (PC). The anionic
      phospholipids (PS and PG) promoted the aggregation of L55P TTR by accelerating
      the nucleation phase of aggregation, whereas the zwitterionic phospholipid PC had
      little effect. These results suggest that cholesterol and anionic phospholipids
      may be important for TTR aggregation and TTR-induced cytotoxicity.

PMID- 18061141
TI  - Expression, regulation and function of trail in atherosclerosis.
AB  - Atherosclerosis is a condition where vascular smooth muscle cells (VSMCs),
      inflammatory cells, lipids, cholesterol and cellular waste accumulate in the
      inner lining of an artery, producing a fibro-fatty plaque and resulting in the
      thickening of the arterial wall. The tumor necrosis factor (TNF) family of
      cytokines plays a major role in the progression of atherosclerosis. Recently, TNF
      related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, has
      been implicated in the development of atherosclerosis since it has been detected
      in normal and diseased atherosclerotic tissue. Not only is TRAIL involved in
      apoptosis and immune regulation, recent studies have provided a new function of
      TRAIL on vascular cells, such that TRAIL can promote endothelial cell (EC) and
      VSMCs migration and proliferation. In addition, TRAIL is implicated in regulating
      vascular tone. This review discusses our current understanding of TRAIL
      expression, regulation and function, and summarises the recent data implicating a
      role for TRAIL in atherosclerosis.

PMID- 18061142
TI  - On the energy-dependence of Hoechst 33342 transport by the ABC transporter LmrA.
AB  - LmrA is an ATP-binding cassette (ABC) multidrug transporter from Lactococcus
      lactis, and is a structural homologue of the human multidrug resistance P
      glycoprotein (ABCB1), the overexpression of which is associated with multidrug
      resistance in tumours. We recently observed that a truncated version of LmrA
      lacking the nucleotide-binding domain mediates a proton motive force-dependent
      ethidium transport reaction by catalyzing proton-ethidium symport. This finding
      raised the question whether proton motive force-dependent transport can also be
      observed for other drugs, and whether this reaction is also relevant for full
      length LmrA. Furthermore, the observations on LmrA-MD raised the question whether
      ATP-dependent transport by LmrA in intact cells could be due to the activity of
      independent ABC transporters that might become upregulated in the lactococcal
      cells due to the overexpression of LmrA; the recently identified ABC multidrug
      transporter LmrCD was put forward as a possible candidate. Here, we investigated
      the energy coupling to the transport of the amphiphilic dye Hoechst 33342 in
      proteoliposomes containing purified LmrA. For this purpose, LmrA was obtained
      from lactococcal cells lacking the genomic lmrA and lmrCD genes, in which LmrA
      was expressed from a plasmid. To separate ATP-dependence from proton motive force
      dependence, we also used mutant LmrA proteins, which were affected in their
      ability to hydrolyse ATP. Our studies in proteoliposomes demonstrate that LmrA
      can catalyze Hoechst 33342 transport independent of auxiliary proteins, in an ATP
      dependent fashion and a transmembrane chemical proton gradient (interior acidic)
      dependent fashion.

PMID- 18061143
TI  - Cyclo(dehydrohistidyl-l-tryptophyl) inhibits nitric oxide production by
      preventing the dimerization of inducible nitric oxide synthase.
AB  - Dimerization of inducible NOS has been known to be a potential therapeutic target
      for iNOS-mediated pathologies. Cyclic dipeptides are among the simplest peptides
      commonly found as by-products of food processing or metabolites of
      microorganisms. In this study, we found that cyclo(dehydrohistidyl-l-tryptophyl)
      (CDHT), a cyclic dipeptide from an unidentified fungal strain Fb956, prevents
      iNOS dimerization in activated microglial BV-2 cells. CDHT inhibited NO
      production with an IC50 of 6.5 microM in LPS-treated BV-2 cells. Western blot
      analysis and iNOS activity measurement of fractions from size-exclusion
      chromatography of cell lysates indicated that CDHT inhibits dimerization of iNOS,
      while it has no effect on iNOS expression or enzyme activity. The CDHT inhibition
      of iNOS dimerization was confirmed by partially denaturing SDS-PAGE analysis. In
      contrast, CDHT did not affect cGMP production in endothelial HUVEC cells, which
      indicates no inhibition of endothelial NOS activity. These results reveal that
      CDHT, one of the simplest and cyclic dipeptides, selectively inhibits NO
      production by inhibiting iNOS dimerization, and could be a useful therapeutic
      agent for inflammation-mediated diseases.

PMID- 18061144
TI  - Next generation topoisomerase I inhibitors: Rationale and biomarker strategies.
AB  - Topoisomerase I (TopoI), an essential enzyme, produces a DNA single strand break
      allowing DNA relaxation for replication. The enzymatic mechanism involves
      sequential transesterifcations. The breakage and closure reactions generate
      phosphodiester bonds and similar free energies, so the reaction is freely
      reversible. The TopoI reaction intermediate consists of enzyme covalently linked
      to DNA dubbed a 'cleavable complex'. Covalently bound TopoI-DNA complexes can be
      recovered. Camptothecin analogs, topotecan and irinotecan, are approved TopoI
      targeted drugs. Both have limitations due to the equilibrium between the
      camptothecin lactone and ring-opened forms. Several strategies are being explored
      to develop improved TopoI inhibitors. Homocamptothecins, in which the
      metabolically labile camptothecin lactone is replaced with a more stable seven
      membered beta-hydroxylactone, are potent anticancer agents. Gimatecan is a seven
      position modified lipophilic camptothecin developed to provide rapid uptake and
      accumulation in cells and a stable TopoI-DNA-drug ternary complex. Diflomotecan,
      a homocamptothecin, and gimatecan are in Phase II clinical trial. Among non
      camptothecins, edotecarin, an indolocarbazole that results in DNA C/T-G cleavage
      compared with T-G/A for camptothecins, is in Phase II clinical trial.
      Indenoisoquinolines were identified as TopoI inhibitors by the NCI 60-cell line
      COMPARE analysis. Co-crystal structures of two indenoisoquinolines with TopoI-DNA
      elucidated the structure of the ternary complex. Indenoisoquinolines are in
      preclinical development. Dibenzonaphthyridinone TopoI inhibitors have undergone
      extensive structure-activity examination. ARC-111 was selected for in-depth
      preclinical study. Biomarkers are under investigation to predict clinical
      efficacy from preclinical models, to allow determination of drug targeting in
      vivo and to aid selection of patients most likely to benefit from TopoI inhibitor
      therapy. gamma-H2AX formation may be a useful pharmacodynamic marker. A gene
      signature developed for topotecan sensitivity/resistance may have value in
      patient identification. Convergence of these efforts should result in clinically
      effective second generation TopoI inhibitors.

PMID- 18061145
TI  - Activation of raphe efferents to the medial prefrontal cortex by corticotropin
      releasing factor: correlation with anxiety-like behavior.
AB  - BACKGROUND: Parallel lines of research suggest that dysfunction affecting both
      corticotropin-releasing factor (CRF) and serotonin (5-HT) systems is involved in
      the pathophysiology of psychiatric illnesses such as anxiety and depression. The
      effect of CRF on behavior and on the accompanying change in activity of 5-HT
      neurons in the dorsal and median raphe nuclei (DR and MR) that project to the
      ventral medial prefrontal cortex (mPFC), a brain area implicated in mood and
      anxiety disorders, was studied. METHODS: Male Sprague-Dawley rats with intra-mPFC
      deposits of fluorescent microspheres received injections of CRF (1 microg,
      intracerebroventricular [i.c.v.]) and were tested for CRF-enhanced startle, a
      behavioral assay believed to reflect stress- or anxiety-like states. C-Fos
      immunohistochemistry was used to measure CRF-induced activity in retrogradely
      labeled neurons in the DR and MR and correlate this level of activity with the
      level of CRF-enhanced startle. RESULTS: The CRF-enhanced startle was accompanied
      by an increased c-Fos expression in retrogradely labeled cells in the raphe. In
      the DR and MR, there was a clear topography of activation, with a higher-percent
      activation in retrogradely labeled neurons in caudal sections. In the caudal DR,
      this effect was positively correlated with the level of CRF-enhanced startle. Co
      expression of retrogradely labeled cells with tryptophan hydroxylase showed that
      the majority (> 90%) of raphe efferents to the mPFC were from serotonergic
      neurons. CONCLUSIONS: These data indicate that CRF activates a subpopulation of
      cortical-projecting 5-HT raphe neurons and suggest that increased 5-HT release in
      the mPFC might be an important component driving some types of anxiety-like
      behaviors.

PMID- 18061146
TI  - Proton magnetic resonance spectroscopy measurement of brain glutamate levels in
      premenstrual dysphoric disorder.
AB  - BACKGROUND: Women who suffer from premenstrual dysphoric disorder (PMDD)
      classically display depressive and anxiety symptoms in the premenstrum.
      Preclinical and clinical studies have suggested a role of glutamate in anxiety
      and depression. This investigation aims at demonstrating fluctuations of
      glutamate across the menstrual cycle in the medial prefrontal cortex of women who
      suffer from PMDD and healthy control subjects (HCs). METHODS: Twelve PMDD women
      and 13 HCs were randomized to two single-voxel 3 Tesla proton magnetic resonance
      spectroscopy examinations of the medial prefrontal cortex during the follicular
      phase and the luteal phase. RESULTS: A phase effect was observed; the levels of
      glutamate/creatine plus phosphocreatine (Cr) were significantly lower during the
      luteal phase compared with the follicular phase. However, no statistically
      significant diagnosis or phase x diagnosis effects were found. CONCLUSIONS: The
      optimized stimulated echo acquisition mode (STEAM) pulse timings selected in this
      study (echo time [TE], mixing time [TM] = 240, 27 msec) allow us to interpret our
      results as the first report of alterations of brain glutamate levels across the
      menstrual cycle. Hormonal fluctuations associated with the menstrual cycle likely
      contribute to these glutamate level variations. Although PMDD women undergo a
      similar decrease in glutamate during the luteal phase as the HCs, PMDD women may
      display an increased behavioral sensitivity to those phase-related alterations.
      These menstrual cycle-related variations of glutamate levels may also contribute
      to the influence of the phases of the menstrual cycle in other neuropsychiatric
      disorders.

PMID- 18061147
TI  - Electroencephalographic alpha measures predict therapeutic response to a
      selective serotonin reuptake inhibitor antidepressant: pre- and post-treatment
      findings.
AB  - BACKGROUND: There is growing evidence that individual differences among depressed
      patients on electrophysiologic (EEG), neuroimaging, and neurocognitive measures
      are predictive of therapeutic response to antidepressant drugs. This study
      replicates prior findings of pretreatment differences between selective serotonin
      reuptake inhibitor (SSRI) responders and nonresponders in EEG alpha power or
      asymmetry and examines whether these differences normalize or are stable after
      treatment. METHODS: Resting EEG (eyes open and closed) was recorded from 28
      electrodes (nose reference) in 18 depressed patients when off medication and at
      the end of 12 weeks of fluoxetine treatment. Clinical response was assessed by an
      independent rater with the Clinical Global Impression Improvement scale. The EEG
      data were also obtained for 18 healthy adults matched to patients in gender and
      age. RESULTS: Treatment responders had greater alpha power compared with
      nonresponders and healthy control subjects, with largest differences at occipital
      sites where alpha was largest. There were also differences in alpha asymmetry
      between responders and nonresponders at occipital sites. Responders showed
      greater alpha (less activity) over right than left hemisphere, whereas
      nonresponders tended to show the opposite asymmetry. Neither alpha power nor
      asymmetry changed after treatment, and test-retest correlations were high,
      particularly for alpha power. Alpha power and asymmetry showed reasonable
      positive predictive value but less negative predictive value. CONCLUSIONS: The
      findings confirm reports of alpha differences between antidepressant responders
      and nonresponders and raise hopes for developing EEG tests for selecting
      effective treatments for patients. The stability of alpha power and asymmetry
      differences between SSRI responders and nonresponders after treatment suggests
      that they represent state-independent characteristics.

PMID- 18061148
TI  - Pericyte-endothelial cell interaction increases MMP-9 secretion at the blood
      brain barrier in vitro.
AB  - The extracellular matrix (ECM) connecting brain capillary endothelial cells
      (BCEC) with the surrounding brain resident cells is an essential part of the
      blood-brain barrier (BBB). Represented by the basement membrane which joins BCEC
      with brain neuroglia (astrocytes and pericytes) it forms a neurovascular unit.
      Neuroglia-secreted matrix metalloproteinases (MMPs) control the ECM composition
      and are involved in the integrity and function of the BBB during cell diapedesis
      and BBB breakdown after ischemia and other CNS diseases. We examined the
      involvement of pericytes and astrocytes in endothelial MMP secretion and their
      effect on endothelial barrier properties in a primary cell culture model using
      porcine BCEC. We applied puromycin to eliminate pericyte growth and demonstrated
      a significant (to about 30%) reduction of endothelial MMP-9 production in
      pericyte-free cultures. In contrast, BCEC co-culture with pericytes resulted in
      an increased amount of endothelial MMP-9 and active MMPs measured by both
      zymography and fluorimetric assay. Astrocyte co-culture in a filter setup with
      BCEC allowing a cell-cell signaling via soluble factors revealed significantly
      reduced endothelial MMP activity. These data were directly correlated with
      improved BBB integrity under pericyte elimination and astrocyte co-culture
      conditions as indicated by transendothelial electrical resistance (TEER) values.
      Our data define pericyte interactions as a main inducer of endothelial MMP
      secretion and propose a new role for pericyte-endothelial cell crosstalk at the
      BBB in vitro.

PMID- 18061149
TI  - Acoustic modulation of immediate early gene expression in the auditory midbrain
      of female tungara frogs.
AB  - To better understand the molecular consequences of auditory processing in frogs,
      we investigated the acoustic modulation of two immediate early genes (IEGs), egr
      1 and fos, in the auditory midbrain of female tungara frogs. Since tungara frog
      egr-1 had already been identified, we first isolated a tungara-specific fos clone
      using degenerate PCR followed by Rapid Amplification of cDNA Ends. In order to
      examine the temporal kinetics of acoustically modulated IEG mRNA expression, we
      first acoustically isolated females collected from a mating chorus and analyzed
      the decline in IEG expression in the torus semicircularis (homolog of the
      inferior colliculus). We found that IEG mRNA levels declined rapidly and reached
      baseline within 2 h. Next, we presented females with a 30-min recording of a
      mating chorus and analyzed IEG expression following different survival times. We
      found that IEG expression increased within 15-30 min of sound presentation but,
      compared to other vertebrates, in the tungara frog it took longer to reach the
      highest and lowest mRNA levels in response to sound and isolation, respectively.
      We also found that acoustic stimulation of egr-1 and fos differed in the three
      subdivisions of the torus semicircularis, suggesting that, as in birds, the two
      genes could provide largely different information when used in IEG mapping
      studies. While our results confirm the generality of sensory-induced IEG
      expression in vertebrates, whether the longer time course of IEG expression that
      we observed represents a species difference in the mechanisms of IEG
      transcription awaits further study.

PMID- 18061150
TI  - Complex I deficiency in Parkinson's disease frontal cortex.
AB  - A study of complex I (NADH:ubiquinone oxidoreductase) activity in Parkinson's
      disease (PD) brain has identified loss of activity only in substantia nigra
      although loss of activity of this enzyme has been identified in a number of non
      brain tissues. We investigated this paradox by studying complex I and other
      complexes of the mitochondrial electron transport chain in frontal cortex from PD
      and aged control brain using a variety of assay conditions and tissue
      preparations. We found increasingly significant losses of complex I activity in
      PD frontal cortex as increasingly pure mitochondria were studied. Complexes II,
      III, and IV were comparable in PD and controls. Inclusion of bovine serum albumin
      in the assay increased enzyme activity but lessened discrimination between PD and
      controls. Complex I deficiency in PD brain is not confined to substantia nigra.
      Methodological issues are critical in demonstrating this loss of activity.

PMID- 18061151
TI  - Mitochondrial dysfunction in mouse trisomy 16 brain.
AB  - Mitochondrial function in the brain of mouse trisomy 16, an animal model of Down
      syndrome with accelerated neuron death, was studied in isolated cortex
      mitochondria. Using an oxygen-sensitive Clarke electrode, a selective 16%
      decrease in respiration was detected with the Complex I substrates malate and
      glutamate but not with the Complex II substrate succinate. Western blotting
      revealed a 20% decrease in the 20 kDa subunit of Complex I in Ts16 brain cortex
      homogenates with no significant decrease in marker proteins for the other
      complexes of the electron transport chain. Although no differences in H(2)O(2)
      production or maximal calcium uptake were detected in the Ts16 mitochondria,
      there was an 18% decrease in pyruvate dehydrogenase levels, a change associated
      with oxidative stress in ischemia. These results are similar to those found in
      Parkinson's disease suggesting some neurodegenerative diseases may have
      mitochondrial pathology as a common step.

PMID- 18061152
TI  - Activation of the posterior cingulate by semantic priming: a co-registered
      ERP/fMRI study.
AB  - Although the N400 is the best understood semantically sensitive component of the
      event-related potential (ERP), others have been observed as well. In an earlier
      lexical decision study, an N300 ERP was found to be enhanced to unprimed targets,
      although the effect could also be characterized as a prolonged P2 to primed
      targets as described in other reports. Because its scalp topography suggested its
      neural source might be of interest, a source localization was conducted that
      suggested that this component emanated from the dorsal posterior cingulate cortex
      (dPCC). In order to confirm this word N300 localization, a functional magnetic
      resonance imaging (fMRI) study was conducted to replicate the ERP study with a
      separate sample of 17 participants in an event-related design, using a 3-T
      scanner. A significant activation in the right dPCC was found corresponding to
      the N300 localization. The activation was greater on the related prime trials,
      supporting the characterization of the ERP component as being a P2 rather than an
      N300. A review is provided which suggests that a number of separate lines of ERP
      research regarding the word N300, the picture N300, the word P2, the phonological
      mismatch negativity, and the word midline frontal negativity may be most
      parsimoniously regarded as dealing with the same ERP component and that they all
      therefore emanate from the dPCC. It is suggested that this region plays a role in
      stimulus-response mapping in polymodal fashion. It is also suggested that the ERP
      component be termed a P2-dPCC.

PMID- 18061153
TI  - Effects of a B-vitamin-deficient diet on exploratory activity, motor
      coordination, and spatial learning in young adult Balb/c mice.
AB  - Elevated homocysteine levels resulting from vitamin B deficiencies have been
      hypothesized to contribute to functional decline. To investigate the effects of
      elevated serum homocysteine on neurobehavioral performances, young adult Balb/c
      mice consumed a vitamin-B-deficient diet or a control diet under free-feeding and
      pair-fed conditions. The B-deficient diet decreased body weight and food intake
      but increased water ingestion. Relative to either control group, vitamin-B
      deficient mice were more active in the open field and in enclosed arms of the
      elevated plus-maze. However, vitamin-B-deficient mice were not impaired on
      sensorimotor coordination and spatial learning tests, swimming to a visible
      platform even faster than either control group. The main effect of this diet
      restriction was hyperactivity with no change in anxiety, coordination, and
      memory. It remains to be determined whether severer deficits are demonstrable in
      older mice.

PMID- 18061154
TI  - The presence of GM-CSF and IL-4 interferes with effect of TGF-beta1 on antigen
      presenting cells in patients with multiple sclerosis and in rats with
      experimental autoimmune encephalomyelitis.
AB  - The possibility to generate and expand tolerogenic dendritic cells (DC) with TGF
      beta1 in vitro opens new therapeutic perspectives for the treatment of autoimmune
      diseases. In the present study, GM-CSF+IL-4 induced the differentiation of DC
      from adherent peripheral blood mononuclear cells, which had a higher expression
      of HLA-DR, CD86 and CD1a and the capacity to stimulate T cells. TGF-beta1 alone
      slightly promoted the generation of antigen presenting cells (APC) with higher
      expression of CD14, but did not differentiate them into E-cadherin+Langerhans
      cell (LC)-like DC. TGF-beta1-driven APC exhibited the morphology, phenotypes and
      functions of tolerogenic immature DC, and had lower capacity to stimulate T
      cells. In vivo experiment demonstrates that TGF-beta1-treated APC exhibited the
      therapeutic potential in Lewis rats with experimental autoimmune
      encephalomyelitis (EAE), followed by increase of IL-10 production in lymph nodes
      and decrease of inflammatory cells in spinal cords. Most importantly, GM-CSF/IL-4
      used in DC preparation abolished the effect of TGF-beta1 to induce tolerogenic
      APC in vitro and in vivo. The results reveal that the usage of GM-CSF for the
      generation of tolerogenic DC should not be copied from DC preparation for anti
      tumor therapy.

PMID- 18061155
TI  - Estrogen distinctively modulates spleen DC from (NZB x NZW) F1 female mice in
      various disease development stages.
AB  - Estrogen is important in the pathogenesis of systemic lupus erythematosus (SLE).
      The modulation of estrogen on dendritic cells (DCs) may involve in SLE
      development. Our purpose was to find out whether in vitro the effect of estrogen
      on DCs is correlated with the disease progression in vivo. We compared the
      effects of 17beta-estradiol (E2) on spleen DCs from SLE murine model-(NZB x NZW)
      F1 female mice before and after the disease onset. Results showed that E2 changed
      the surface molecule CD40, cytokines IL-6, IL-10, IL-12 and TNFalpha and
      stimulatory ability of spleen DCs from the mice. Selective estrogen receptor
      modulator-tamoxifen (TAM) could antagonize E2 effects and E2 could influence
      estrogen receptor (ER alpha) level in DCs. The changes of DCs from various age
      old mice were different even contrast. So E2 participates in SLE through
      modulating DCs by binding ER alpha. The effects of E2 on DCs from mice in various
      disease progression stages were different.

PMID- 18061156
TI  - Why the verbal counting principles are constructed out of representations of
      small sets of individuals: a reply to Gallistel.

PMID- 18061157
TI  - Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme
      contains self-renewing progenitor cells and gives rise exclusively to nephronic
      epithelia.
AB  - Classic tissue recombination and in vitro lineage tracing studies suggest that
      condensed metanephric mesenchyme (MM) gives rise to nephronic epithelium of the
      adult kidney. However, these studies do not distinguish between cap mesenchyme
      and pre-tubular aggregates comprising the condensed MM, nor do they establish
      whether these cells have self-renewing capacity. To address these questions, we
      generated Cited1-CreER(T2) BAC transgenic mice, which express tamoxifen-regulated
      Cre recombinase exclusively in the cap mesenchyme. Fate mapping was performed by
      crossing these mice with the Rosa26R(LacZ) reporter line and evaluating the
      location and cellular characteristics of LacZ positive cells at different time
      points following tamoxifen injection. These studies confirmed expected results
      from previous in vitro analysis of MM cell fate, and provide in vivo evidence
      that the cap mesenchyme does not contribute to collecting duct epithelium in the
      adult. Furthermore, by exploiting the temporally regulated Cre recombinase, these
      studies show that nephronic epithelium arising at different stages of
      nephrogenesis has distinct spatial distribution in the adult kidney, and
      demonstrate for the first time that the cap mesenchyme includes a population of
      self-renewing epithelial progenitor cells.

PMID- 18061158
TI  - Antenna and all gnathal appendages are similarly transformed by homothorax knock
      down in the cricket Gryllus bimaculatus.
AB  - Our understanding of the developmental mechanisms underlying the vast diversity
      of arthropod appendages largely rests on the peculiar case of the dipteran
      Drosophila melanogaster. In this insect, homothorax (hth) and extradenticle (exd)
      together play a pivotal role in appendage patterning and identity. We
      investigated the role of the hth homologue in the cricket Gryllus bimaculatus by
      parental RNA interference. This species has a more generalized morphology than
      Oncopeltus fasciatus, the one other insect besides Drosophila where homothorax
      function has been investigated. The Gryllus head appendages represent the
      morphologically primitive state including insect-typical mandibles, maxillae and
      labium, structures highly modified or missing in Oncopeltus and Drosophila. We
      depleted Gb'hth function through parental RNAi to investigate its requirement for
      proper regulation of other appendage genes (Gb'wingless, Gb'dachshund,
      Gb'aristaless and Gb'Distalless) and analyzed the terminal phenotype of Gryllus
      nymphs. Gb'hth RNAi nymphs display homeotic and segmentation defects similar to
      hth mutants or loss-of-function clones in Drosophila. Intriguingly, however, we
      find that in Gb'hth RNAi nymphs not only the antennae but also all gnathal
      appendages are homeotically transformed, such that all head appendages
      differentiate distally as legs and proximally as antennae. Hence, Gb'hth is not
      specifically required for antennal fate, but fulfills a similar role in the
      specification of all head appendages. This suggests that the role of hth in the
      insect antenna is not fundamentally different from its function as cofactor of
      segment-specific homeotic genes in more posterior segments.

PMID- 18061159
TI  - Robo-Slit interactions regulate longitudinal axon pathfinding in the embryonic
      vertebrate brain.
AB  - The early network of axons in the embryonic brain provides connectivity between
      functionally distinct regions of the nervous system. While many of the molecular
      interactions driving commissural pathway formation have been deciphered, the
      mechanisms underlying the development of longitudinal tracts remain unclear. We
      have identified here a role for the Roundabout (Robo) family of axon guidance
      receptors in the positioning of longitudinally projecting axons along the
      dorsoventral axis in the embryonic zebrafish forebrain. Using a loss-of-function
      approach, we established that Robo family members exhibit complementary functions
      in the tract of the postoptic commissure (TPOC), the major longitudinal tract in
      the forebrain. Robo2 acted initially to split the TPOC into discrete fascicles
      upon entering a broad domain of Slit1a expression in the ventrocaudal
      diencephalon. In contrast, Robo1 and Robo3 restricted the extent of
      defasciculation of the TPOC. In this way, the complementary roles of Robo family
      members balance levels of fasciculation and defasciculation along this
      trajectory. These results demonstrate a key role for Robo-Slit signaling in
      vertebrate longitudinal axon guidance and highlight the importance of context
      specific guidance cues during navigation within complex pathways.

PMID- 18061160
TI  - A spatially dynamic cohort of regulatory genes in the endomesodermal gene network
      of the sea urchin embryo.
AB  - A gene regulatory network subcircuit comprising the otx, wnt8, and blimp1 genes
      accounts for a moving torus of gene expression that sweeps concentrically across
      the vegetal domain of the sea urchin embryo. Here we confirm by mutation the
      inputs into the blimp1cis-regulatory module predicted by network analysis. Its
      essential design feature is that it includes both activation and autorepression
      sites. The wnt8 gene is functionally linked into the subcircuit in that cells
      receiving this ligand generate a beta-catenin/Tcf input required for blimp1
      expression, while the wnt8 gene in turn requires a Blimp1 input. Their torus-like
      spatial expression patterns and gene regulatory analysis indicate that the genes
      even-skipped and hox11/13b are also entrained by this subcircuit. We verify the
      cis-regulatory inputs of even-skipped predicted by network analysis. These
      include activation by beta-catenin/Tcf and Blimp1, repression within the torus by
      Hox11/13b, and repression outside the torus by Tcf in the absence of Wnt8 signal
      input. Thus even-skipped and hox11/13b, along with blimp1 and wnt8, are members
      of a cohort of torus genes with similar regulatory inputs and similar, though
      slightly out-of-phase, expression patterns, which reflect differences in cis
      regulatory design.

PMID- 18061161
TI  - The cell surface receptor FGFRL1 forms constitutive dimers that promote cell
      adhesion.
AB  - FGFRL1 is a novel member of the fibroblast growth factor (FGF) receptor family.
      Utilizing the FRET (fluorescence resonance energy transfer) technique, we
      demonstrate that FGFRL1 forms constitutive homodimers at cell surfaces. The
      formation of homodimers was verified by co-precipitation of differentially tagged
      FGFRL1 polypeptides from solution. If overexpressed in cultivated cells, FGFRL1
      was found to be enriched at cell-cell contact sites. The extracellular domain of
      recombinant FGFRL1 promoted cell adhesion, but not cell spreading, when coated on
      plastic surfaces. Adhesion was mediated by heparan sulfate glycosaminoglycans
      located at the cell surface. It could specifically be blocked by addition of
      soluble heparin but not by addition of other glycosaminoglycans. When the amino
      acid sequence of the putative heparin-binding site was modified by in vitro
      mutagenesis, the resulting protein exhibited decreased affinity for heparin and
      reduced activity in the cell-binding assay. Moreover, a synthetic peptide
      corresponding to the heparin-binding site was able to neutralize the effect of
      heparin. With its dimeric structure and its adhesion promoting properties, FGFRL1
      resembles the nectins, a family of cell adhesion molecules found at cell-cell
      junctions.

PMID- 18061162
TI  - TNF alpha acting on TNFR1 promotes breast cancer growth via p42/P44 MAPK, JNK,
      Akt and NF-kappa B-dependent pathways.
AB  - Tumor necrosis factor alpha (TNF alpha) enhances proliferation of chemically
      induced mammary tumors and of T47D human cell line through not fully understood
      pathways. Here, we explored the intracellular signaling pathways triggered by TNF
      alpha, the participation of TNF alpha receptor (TNFR) 1 and TNFR2 and the
      molecular mechanism leading to breast cancer growth. We demonstrate that TNFalpha
      induced proliferation of C4HD murine mammary tumor cells and of T47D cells
      through the activation of p42/p44 MAPK, JNK, PI3-K/Akt pathways and nuclear
      factor-kappa B (NF-kappa B) transcriptional activation. A TNF alpha-specific
      mutein selectively binding to TNFR1 induced p42/p44 MAPK, JNK, Akt activation, NF
      kappa B transcriptional activation and cell proliferation, just like wild-type
      TNF alpha, while a mutein selective for TNFR2 induced only p42/p44 MAPK
      activation. Interestingly, blockage of TNFR1 or TNFR2 with specific antibodies
      was enough to impair TNF alpha signaling and biological effect. Moreover, in vivo
      TNF alpha administration supported C4HD tumor growth. We also demonstrated, for
      the first time, that injection of a selective inhibitor of NF-kappa B activity,
      Bay 11-7082, resulted in regression of TNF alpha-promoted tumor. Bay 11-7082
      blocked TNF alpha capacity to induce cell proliferation and up-regulation of
      cyclin D1 and of Bcl-xLin vivo and in vitro. Our results reveal evidence for TNF
      alpha as a breast tumor promoter, and provide novel data for a future therapeutic
      approach using TNF alpha antagonists and NF-kappa B pharmacological inhibitors in
      established breast cancer treatment.

PMID- 18061163
TI  - The hnRNP and cytoskeletal protein raver1 contributes to synaptic plasticity.
AB  - Raver1 is an hnRNP protein that interacts with the ubiquitous splicing regulator
      PTB and binds to cytoskeletal components like alpha-actinin and
      vinculin/metavinculin. Cell culture experiments suggested that raver1 functions
      as corepressor in PTB-regulated splicing reactions and may thereby increase
      proteome complexity. To determine the role of raver1 in vivo, we inactivated the
      gene by targeted disruption in the mouse. Here we report that raver1-deficient
      mice develop regularly to adulthood and show no obvious anatomical or behavioral
      defects. In keeping with this notion, cells from raver1-null mice were
      indistinguishable from wild type cells and displayed normal growth, motility, and
      cytoskeletal architecture in culture. Moreover, alternative splicing of exons,
      including the model exon 3 of alpha-tropomyosin, was not markedly changed in
      mutant mice, suggesting that the role of raver1 for PTB-mediated exon repression
      is not absolutely required to generate splice variants during mouse development.
      Interestingly however, loss of raver1 caused significantly reduced plasticity of
      synapses on acute hippocampal slices, as elicited by electrophysiological
      measurements of markedly lower LTP and LTD in mutant neurons. Our results provide
      evidence that raver1 may play an important role for the regulation of neuronal
      synaptic plasticity, possibly by controlling especially the late LTP via
      posttranscriptional mechanisms.

PMID- 18061165
TI  - The activation of MEK-ERK1/2 by glutamate receptor-stimulation is involved in the
      regulation of RPE proliferation and morphologic transformation.
AB  - Retinal pigment epithelial (RPE) cells are the main cell type involved in the
      pathogenesis of proliferative vitreoretinopathy (PVR). As a result from retinal
      detachment or surgical procedures, RPE comes in contact with glutamate from
      serum, glial release and the injured retina. The purpose of this study was to
      explore a possible role for glutamate in the development of PVR, mediated by the
      receptor-stimulated activation of the ERK1/2 MAPK pathway, the alteration of cell
      proliferation and the transdifferentiation of RPE cells, using rat RPE cells in
      culture as a model system. We demonstrated the expression in these cells of Group
      I metabotropic-and ionotropic AMPA/KA and NMDA glutamate receptors (GluRs),
      predominantly of the NMDA subtype, which are targeted to the membrane, and
      exhibit pharmacological and biochemical characteristics equivalent to those
      previously established in brain tissue. Proliferation was measured by MTS
      reduction colorimetric assay, and actin cytoskeleton dynamics was visualized by
      immunoflurescence using alpha-sma specific antibodies. Activation of
      metabotropic, AMPA and NMDA receptors by glutamate induced the time-and dose
      dependent phosphorylation of ERK1/2, assessed by Western blot analysis, in
      parallel to a significant increase in cell proliferation and a decrease in alpha
      sma expression and its recruitment into stress fibers. These effects were all
      prevented by the inhibition of MEK. Hence, results suggest that glutamate could
      be involved in the generation of PVR, through a GluR-mediated increase in
      proliferation and phenotypic transformation, cause-effect related to the
      activation of ERK1/2.

PMID- 18061164
TI  - Induction of interleukin-6 in human retinal epithelial cells by an attenuated
      Herpes simplex virus vector requires viral replication and NFkappaB activation.
AB  - Gene delivery has potential for treating ocular disease and a number of delivery
      systems have been tested in animal models. However, several viral vectors have
      been shown to trigger undesirable transient inflammatory responses in the eye.
      Previously, it was shown that an attenuated Herpes simplex virus vector (hrR3)
      transduced numerous cell types in the anterior and posterior segments of monkey
      eyes, but this was accompanied by inflammation. In the retina, retinal pigment
      epithelial cells were the predominant cell type transduced by hrR3. IL-6 is an
      important pro-inflammatory cytokine and may play a role in the response to the
      hrR3 vector. Infection of human ARPE-19 cells with hrR3 resulted in increased IL
      6 expression and secretion 3-4h post-infection. In the presence of acyclovir (70
      microM) or in cells infected with UV-inactivated hrR3, IL-6 was not up-regulated
      indicating viral replication was required. Expression of the HSV-1 alpha and beta
      genes may be necessary but was not sufficient for NF-kappaB activation and IL-6
      up-regulation. The translocation of NF-kappaB into the nucleus also occurred
      between 3 and 4h post-infection, coincident with increased IL-6 expression.
      Inhibition of NF-kappaB translocation by an Adenovirus vector expressing a
      dominant negative IkappaB (AdIkappaBam) inhibited IL-6 up-regulation, indicating
      that NF-kappaB plays a role in increasing IL-6 expression in APRE-19 cells. The
      hrR3 virus lacks viral ribonucleotide reductase (RR) activity, thus RR is not
      required for NF-kappaB activation or IL-6 up-regulation in ARPE-19 cells.

PMID- 18061166
TI  - Migration of transplanted neural progenitor cells in a ferret model of cortical
      dysplasia.
AB  - Although altered gene expression clearly causes failure of the neocortex to form
      properly, many causes of neocortical dysplasia arise from environmental or
      unknown factors. Our lab studies a model of cortical dysplasia induced by
      injection of methylazoxymethanol (MAM) into pregnant ferrets on embryonic day 33
      (E33), which shares many features of neocortical dysplasia in humans. E33 MAM
      treatment results in characteristic deficits that include dramatic reduction of
      layer 4 in somatosensory cortex, widespread termination of thalamic afferents,
      and altered distribution of GABAergic elements. We determined the ability of
      immature cells to migrate into MAM-treated cortex using ferret neural progenitor
      cells obtained at E27 and E33 and mouse neural progenitor cells obtained at E14.
      When these cells were transplanted into organotypic cultures obtained from normal
      and E33 MAM-treated ferret cortex prepared on postnatal day 0 (P0), all
      progenitor cells migrated similarly in both hosts, preferentially residing in the
      upper cortical plate. The site of transplantation was significant, however, so
      that injections into the ventricular zone were more likely to reach the cortical
      plate than transplants into the intermediate zone. When similar cells were
      transplanted into ferret kits, approximately P7-P9, and allowed to survive for 2
      4 weeks, the donor cells migrated differently and also reached distinct
      destinations in normal and MAM-treated hosts. MAM-treated cortex was more
      permissive to invasion by donor cells as they migrated to widespread aspects of
      the cortex, whereas transplants in normal host cortex were more restricted. E27
      neural progenitor cells populated more cortical layers than later born E33 neural
      progenitor cells, suggesting that the fate of transplanted cells is governed by a
      combination of extrinsic and intrinsic factors.

PMID- 18061167
TI  - Impact of neonatal asphyxia and hind limb immobilization on musculoskeletal
      tissues and S1 map organization: implications for cerebral palsy.
AB  - Cerebral palsy (CP) is a complex disorder of locomotion, posture and movements
      resulting from pre-, peri- or postnatal damage to the developing brain. In a
      previous study (Strata, F., Coq, J.O., Byl, N.N., Merzenich, M.M., 2004.
      Comparison between sensorimotor restriction and anoxia on gait and motor cortex
      organization: implications for a rodent model of cerebral palsy. Neuroscience
      129, 141-156.), CP-like movement disorders were more reliably reproduced in rats
      by hind limb sensorimotor restriction (disuse) during development rather than
      perinatal asphyxia (PA). To gain new insights into the underpinning mechanisms of
      CP symptoms we investigated the long-term effects of PA and disuse on the hind
      limb musculoskeletal histology and topographical organization in the primary
      somatosensory cortex (S1) of adult rats. Developmental disuse (i.e. hind limb
      immobilization) associated with PA induced muscle fiber atrophy, extracellular
      matrix changes in the muscle, and mild to moderate ankle and knee joint
      degeneration at levels greater than disuse alone. Sensorimotor restricted rats
      with or without PA exhibited a topographical disorganization of the S1 cortical
      hind limb representation with abnormally large, multiple and overlapping
      receptive fields. This disorganization was enhanced when disuse and PA were
      associated. Altered cortical neuronal properties included increased cortical
      responsiveness and a decrease in neuronal selectivity to afferent inputs. These
      data support previous observations that asphyxia per se can generate the
      substrate for peripheral tissue and brain damage, which are worsened by aberrant
      sensorimotor experience during maturation, and could explain the disabling
      movement disorders observed in children with CP.

PMID- 18061168
TI  - Gadofluorine M-enhanced magnetic resonance nerve imaging: comparison between
      acute inflammatory and chronic degenerative demyelination in rats.
AB  - Nerve imaging by magnetic resonance imaging (MRI) is an emerging tool for the
      diagnostic work-up of patients with PNS disorders. We have recently shown that
      the experimental MR contrast agent gadofluorine M (Gf, Bayer Schering Pharma AG,
      Berlin) accumulates in nerves undergoing Wallerian degeneration and in areas of
      acute focal demyelination allowing in-vivo assessment of nerve pathology. The
      exact pathomechanism underlying Gf accumulation in peripheral nerve disorders is
      unknown so far. In the present study we compared nerve signal alterations on T2-w
      and Gf-enhanced T1-w MRI in two different models of acute inflammatory and
      chronic degenerative demyelination: experimental autoimmune neuritis (EAN)
      induced by immunization with PNS myelin and experimental Charcot-Marie-Tooth
      (CMT) disease in rats overexpressing the myelin protein PMP22. During the acute
      stage of inflammation and demyelination, strong Gf enhancement on T1-w MRI was
      seen in nerve roots and peripheral nerves in EAN, which resolved with completed
      remyelination. Similarly, Gf accumulation was seen in CMT rats during early
      stages with active demyelination at 6 weeks while at chronic stages (9 months) Gf
      enhancement decreased despite numerous demyelinated axons and onion bulb
      formation. At all disease stages no signal alterations were seen on T2-w MRI. In
      conclusion, our data show that the novel MR contrast agent Gf, but not Gadolinium
      (Gd)-DTPA, facilitates detection of ongoing demyelination by MR neurography
      independent from the underlying pathology. It appears that the extent of Gf
      enhancement depends on the acuity of demyelination and is probably related to a
      transient disturbance of the blood-nerve barrier. Clinical development of Gf may
      help to further improve the sensitivity of nerve lesion assessment by MRI in
      patients with peripheral neuropathies.

PMID- 18061170
TI  - Isolated spermatogonia protrude active pseudopodia in vitro.
AB  - When dispersed spermatogenic cells obtained by enzymatic digestion from
      prepuberal mice, adult male mice, nonazoospermic men and normospermic men were
      observed live using Normarski optics, it was found that, respectively, 47.4%,
      1.4%, 5.1%, and 2.4% of them protruded active pseudopodia. These cells were 8 to
      10 mum in diameter, had a high N/C ratio, and had one to two prominent nucleoli
      that were close to a distinct nuclear membrane. They showed low alkaline
      phosphatase activities and homogeneous nuclear immunoreactive patterns using
      gamma-H2AX, which suggests that they were spermatogonia.

PMID- 18061169
TI  - Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford
      dopaminergic neuroprotection in a model of Parkinson's disease.
AB  - Adult adipose contains stromal progenitor cells with neurogenic potential.
      However, the stability of neuronal phenotypes adopted by Adipose-Derived Adult
      Stromal (ADAS) cells and whether terminal neuronal differentiation is required
      for their consideration as alternatives in cell replacement strategies to treat
      neurological disorders is largely unknown. We investigated whether in vitro
      neural induction of ADAS cells determined their ability to neuroprotect or
      restore function in a lesioned dopaminergic pathway. In vitro-expanded naive or
      differentiated ADAS cells were autologously transplanted into substantia nigra 1
      week after an intrastriatal 6-hydroxydopamine injection. Neurochemical and
      behavioral measures demonstrated neuroprotective effects of both ADAS grafts
      against 6-hydroxydopamine-induced dopaminergic neuron death, suggesting that pre
      transplantation differentiation of the cells does not determine their ability to
      survive or neuroprotect in vivo. Therefore, we investigated whether equivalent
      protection by naive and neurally-induced ADAS grafts resulted from robust in situ
      differentiation of both graft types into dopaminergic fates. Immunohistological
      analyses revealed that ADAS cells did not adopt dopaminergic cell fates in situ,
      consistent with the limited ability of these cells to undergo terminal
      differentiation into electrically active neurons in vitro. Moreover, re-exposure
      of neurally-differentiated ADAS cells to serum-containing medium in vitro
      confirmed ADAS cell phenotypic instability (plasticity). Lastly, given that gene
      expression analyses of in vitro-expanded ADAS cells revealed that both naive and
      differentiated ADAS cells express potent dopaminergic survival factors, ADAS
      transplants may have exerted neuroprotective effects by production of trophic
      factors at the lesion site. ADAS cells may be ideal for ex vivo gene transfer
      therapies in Parkinson's disease treatment.

PMID- 18061171
TI  - Effect of recombinant human TNF-binding protein-1 and GnRH antagonist on mRNA
      expression of inflammatory cytokines and adhesion and growth factors in
      endometrium and endometriosis tissues in baboons.
AB  - OBJECTIVE: To evaluate the mechanism of action of recombinant human tumor
      necrosis factor (TNF)-binding protein-1 by assessing differential expression of
      messenger RNA (mRNA) for cytokines, matrix metalloproteinases, and growth and
      adhesion factors in baboons. DESIGN: Analysis of gene expression in a prospective
      randomized study. SETTING: University Fertility Center. ANIMAL(S): In the in vivo
      study, 14 baboons were randomly and subcutaneously (SC) treated with either
      phosphate-buffered saline (PBS), GnRH antagonist, or recombinant human TNF
      binding protein-1 at the time of induction. In the ex vivo study, 4 baboons were
      treated by menstrual endometrium that had been incubated randomly with either PBS
      or recombinant human TNF-binding protein-1 before intrapelvic injection.
      INTERVENTION(S): In the in vivo study, analysis of 11 endometrial and 10
      endometriosis biopsies included either PBS (n = 5), GnRH antagonist (n = 8), or
      recombinant human TNF-binding protein-1 (n = 8). In the ex vivo study, 2
      endometrial and 4 endometriosis biopsies were analyzed from 4 baboons. MAIN
      OUTCOME MEASURE(S): The mRNA expression of TNF-alpha, IL-8, IL-6, transforming
      growth factor-beta (TGF-beta), vascular endothelial growth factor, intercellular
      adhesion molecule-1, matrix metalloproteinase-1, and regulated on activation,
      normal T-cell expressed and secreted were investigated using real-time reverse
      transcriptase-polymer chain reaction (PCR). RESULT(S): TGF-beta mRNA expression
      was decreased in endometriotic lesions from baboons treated with recombinant
      human TNF-binding protein-1 when compared with the placebo group. CONCLUSION(S):
      Except TGF-beta, mRNA expression of inflammatory cytokines and adhesion/growth
      factors is not affected in endometrial and endometriosis biopsies from baboons
      after induction of endometriosis combined with either systemic injection of
      recombinant human TNF-binding or GnRH antagonist or ex vivo treatment with
      recombinant human TNF-binding protein-1. Further studies are needed to elucidate
      the mode of action on how inhibition of TNF-alpha activity prevents the
      development of endometriosis.

PMID- 18061172
TI  - Neovagina creation in vaginal agenesis: development of a new laparoscopic
      Vecchietti-based procedure and optimized instruments in a prospective comparative
      interventional study in 101 patients.
AB  - OBJECTIVE: To improve the laparoscopic Vecchietti procedure and optimize
      instrumentation for treatment of congenital vaginal agenesis with a minimum of
      complications and optimal functional outcome, in comparison with the conventional
      laparoscopic Vecchietti procedure. DESIGN: Prospective comparative interventional
      study. SETTING: University hospital. PATIENT(S): One hundred one patients with
      congenital vaginal agenesis. INTERVENTION(S): The interventions compared were [1]
      a new laparoscopic, Vecchietti-based method using vaginoabdominal blunt
      perforation without vesicorectal tunneling and [2] the laparoscopic Vecchietti
      procedure. MAIN OUTCOME MEASURE(S): Duration of surgery and traction, functional
      results, surgical and technical complications. RESULT(S): Without tunneling and
      with new instruments, mean operative time was more than halved, from 113.0 to
      47.5 minutes, with a significantly reduced complication rate for bladder lesions
      and no bowel lesions. Mean traction time was similarly reduced, from 11.7 to 4.8
      days. No instrument-related complications were seen with our new instrument set.
      After 6 months, the longer neovagina of 10.6 cm that was achieved with the new
      method was still 2.5 cm longer than the conventional result. No patients needed
      lubricants or had sustained pain during intercourse. CONCLUSION(S): Our new
      method for neovagina creation resulted in shorter operation and traction times,
      better functional results, and fewer surgical complications and no technical
      ones. It is therefore a safer, shorter, more effective, and less traumatic
      procedure.

PMID- 18061173
TI  - Effects of hormonal treatment on nerve fibers in endometrium and myometrium in
      women with endometriosis.
AB  - OBJECTIVE: To investigate how hormonal treatment can change nerve fiber density
      and to identify types of nerve fibers in endometrium and myometrium in women with
      endometriosis. DESIGN: Laboratory study using human tissue. SETTING: University
      based laboratory. PATIENT(S): Hormonally treated and untreated women with
      endometriosis undergoing hysterectomy or curettage. INTERVENTION(S): Endometrial
      and myometrial tissues were prepared from women with hormonally treated
      endometriosis and women with untreated endometriosis. MAIN OUTCOME MEASURE(S):
      Types and density of nerve fibers in endometrium and myometrium in women with
      hormonally treated and untreated endometriosis were determined
      immunohistochemically. RESULT(S): The nerve fiber density (mean density +/- SD
      per square millimeter) in the functional and the basal layers of endometrium (0.2
      +/- 0.7/mm(2) and 0.9 +/- 1.3/mm(2), respectively) and myometrium (1.5 +/-
      0.8/mm(2)) from women with hormonally treated endometriosis was much lower than
      that of endometrium (functional layer: 11 +/- 5/mm(2), basal layer: 18 +/-
      8/mm(2), respectively) and myometrium (3 +/- 1/mm(2)) from women with untreated
      endometriosis. Nerve growth factor and nerve growth factor receptor p75
      expression was also significantly reduced in women with hormonally treated
      endometriosis compared with women with untreated endometriosis. CONCLUSION(S):
      Hormonal treatment significantly reduced nerve fiber density in endometrium and
      myometrium in women with endometriosis.

PMID- 18061174
TI  - A comparison of letrozole to gonadotropins for ovulation induction in subjects
      with advanced maternal age: a retrospective pilot study.
AB  - This retrospective study was performed to compare the success of ovulation
      induction using letrozole versus gonadotropins in women at least 38 years of age,
      with normal ovarian reserve. Pregnancy and clinical pregnancy rates (PR) were
      statistically higher with gonadotropin than with letrozole stimulation.

PMID- 18061175
TI  - Human parathyroid hormone 1-34 prevents bone loss in experimental biliary
      cirrhosis in rats.
AB  - BACKGROUND & AIMS: Reduced bone mass and increased fracture rate are
      complications of primary biliary cirrhosis (PBC). The effect of intermittent
      administration of human parathyroid hormone (hPTH) 1-34 on bone mass and
      architecture in bile duct-ligated (BDL) rats was studied. METHODS: Six-month-old
      male rats were subjected to BDL or sham operation (SO) and were treated from the
      second postoperative week intermittently with either hPTH 1-34 40 microg/kg per
      day, 80 microg/kg per day, or a vehicle for 4 weeks. Femoral and tibial bones
      were evaluated ex vivo by dual x-ray absorptiometry, microcomputed tomography,
      and histomorphometry. Serum osteocalcin and urinary deoxypyridinoline cross-links
      (DPD) were determined. RESULTS: BDL rats had decreased bone mass compared with SO
      rats as indicated by a 6% decrease in femoral and tibial bone mineral density
      (BMD), 18% reduction in femoral trabecular bone volume (bone volume/total volume
      [BV/TV]), 17% decrease in trabecular thickness, and 10% decrease in tibial
      cortical thickness. The administration of hPTH 1-34 at 40 microg/kg per day
      increased femoral and tibial BMD (9% and 9%), femoral trabecular BV/TV (50%),
      trabecular thickness (50%), tibial cortical thickness (17%), and serum
      osteocalcin (82%). On the other hand, hPTH 1-34 80 microg/kg per day had no
      effect on BMD and tibial cortical thickness, was associated with a smaller
      increase in trabecular BV/TV (24%), and had a higher osteoclast number and DPD
      compared with untreated BDL rats and the lower hPTH 1-34 dose treatment group.
      CONCLUSIONS: BDL rats exhibit loss of bone mass and structure, which can be
      prevented by the intermittent administration of hPTH 1-34, a potential therapy
      for osteoporosis in PBC.

PMID- 18061176
TI  - Pancreatic cancer-associated diabetes mellitus: prevalence and temporal
      association with diagnosis of cancer.
AB  - BACKGROUND & AIMS: The temporal association between diabetes mellitus and
      pancreatic cancer is poorly understood. We compared temporal patterns in diabetes
      prevalence in pancreatic cancer and controls. METHODS: We reviewed the medical
      records of pancreatic cancer cases residing within 120 miles or less of
      Rochester, Minnesota, seen at the Mayo Clinic between January 15, 1981, and July
      9, 2004, and approximately 2 matched controls/case residing locally. We
      abstracted all outpatient fasting blood glucose (FBG) levels for up to 60 months
      before index (ie, date of cancer diagnosis for cases) and grouped them into 12
      month intervals; 736 cases and 1875 controls had 1 or more outpatient FBG levels
      in the medical record. Diabetes was defined as any FBG level of 126 mg/dL or
      greater or treatment for diabetes, and was defined as new onset when criteria for
      diabetes were first met 24 or fewer months before index, with at least 1 prior
      FBG level less than 126 mg/dL. RESULTS: A higher proportion of pancreatic cancer
      cases compared with controls met the criteria for diabetes at any time in the 60
      months before index (40.2% vs 19.2%, P < .0001). The proportions were similar in
      the -60 to -48 (P = .76) and -48 to -36 (P = .06) month time periods; however, a
      greater proportion of cases than controls met criteria for diabetes in the -36 to
      -24 (P = .04), -24 to -12 (P < .001), and -12 to 0 (P < .001) month time periods.
      Diabetes was more often new onset in cases vs controls (52.3% vs 23.6%, P <
      .0001). CONCLUSIONS: Diabetes has a high (40%) prevalence in pancreatic cancer
      and frequently is new onset. Identification of a specific biomarker for
      pancreatic cancer-induced diabetes may allow screening for pancreatic cancer in
      new-onset diabetes.

PMID- 18061178
TI  - American Gastroenterological Association (AGA) Institute technology assessment on
      image-enhanced endoscopy.
AB  - This document presents the official recommendations of the American
      Gastroenterological Association (AGA) Institute Technology Assessment on "Image
      Enhanced Endoscopy." It was approved by the Clinical Practice and Economics
      Committee on August 3, 2007, and by the AGA Institute Governing Board September
      27, 2007.

PMID- 18061177
TI  - PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation.
AB  - BACKGROUND & AIMS: KPV is a tripeptide (Lys-Pro-Val), which possesses anti
      inflammatory properties; however, its mechanisms of action still remain unknown.
      PepT1 is a di/tripeptide transporter normally expressed in the small intestine
      and induced in colon during inflammatory bowel disease (IBD). The aim of this
      study was to 1) investigate whether the KPV anti-inflammatory effect is PepT1
      mediated in intestinal epithelian and immune cells, and 2) examine the anti
      inflammatory effects in two models of mice colitis. METHODS: Human intestinal
      epithelial cells Caco2-BBE, HT29-Cl.19A, and human T cells (Jurkat) were
      stimulated with pro-inflammatory cytokines in the present or absence of KPV. KPV
      anti-inflammatory effect was assessed using a NF-kappaB luciferase gene reporter,
      Western blot, real-time RT-PCR and ELISA. Uptake experiments were performed using
      cold KPV as a competitor for PepT1 radiolabelled substrate or using [(3)H]KPV to
      determine kinetic characteristics of KPV uptake. Anti-inflammatory effect of KPV
      was also investigated in DSS- and TNBS-induced colitis in mice. KPV was added to
      drinking water and inflammation was assessed at the histologic level and by
      proinflammatory cytokine mRNA expression. RESULTS: Nanomolar concentrations of
      KPV inhibit the activation of NF-kappaB and MAP kinase inflammatory signaling
      pathways, and reduce pro-inflammatory cytokine secretion. We found that KPV acts
      via PepT1 expressed in immune and intestinal epithelial cells. Furthermore, oral
      administration of KPV reduces the incidence of DSS- and TNBS-induced colitis
      indicated by a decrease in pro-inflammatory cytokine expression. CONCLUSIONS:
      This study indicates tht KPV is transported into cells by PepT1 and might be a
      new therapeutic agent for IBD.

PMID- 18061179
TI  - A prominent role for mucosal cystine/cysteine metabolism in intestinal
      immunoregulation.
AB  - BACKGROUND & AIMS: T-cell receptor reactivity of intestinal lamina propria T
      cells (LP-T) critically depends on the capacity of local accessory cells to
      secrete cysteine. For T cells, cysteine is the limiting precursor for glutathione
      synthesis, a prerequisite for antigen-dependent proliferation. We aimed to
      determine the role of the redoxactive microenvironment for hyporeactivity of LP-T
      in normal human gut vs hyperreactivity of LP-T in inflammatory bowel disease.
      METHODS: Parameters relevant to cysteine production, determined as acid-soluble
      thiol, by intestinal lamina propria macrophages (LP-MO) vs peripheral blood
      monocytes were investigated (L-[(35)S]cystine uptake via system x(c)(-),
      messenger RNA, and protein expression of the cystine transporter subunit xCT).
      Glutathione levels in LP-T and peripheral blood T cells were analyzed both
      spectrophotometrically and by immunofluorescent staining in situ and in vitro.
      RESULTS: LP-MO from normal gut, unlike peripheral blood monocytes, are unable to
      take up cystine, which is due to a deficient expression of the transporter xCT in
      situ and in vitro. As a consequence, LP-MO do not secrete cysteine. The
      glutathione content in LP-T from normal gut is <50% of that in autologous
      peripheral blood T cells. In contrast, in inflammatory bowel disease,
      CD14(+)CD68(+) LP-MO express xCT and secrete substantial amounts of cysteine upon
      stimulation, which results in high glutathione levels and full T-cell receptor
      reactivity in LP-T. CONCLUSIONS: The antioxidative microenvironment of LP-T in
      inflammatory bowel disease and the prooxidative microenvironment in normal gut
      explain the differential T-cell receptor reactivities.

PMID- 18061180
TI  - Artificial neural network as a predictive instrument in patients with acute
      nonvariceal upper gastrointestinal hemorrhage.
AB  - BACKGROUND & AIMS: Triage of patients with acute upper gastrointestinal
      hemorrhage (UGIH) has traditionally required urgent upper endoscopy. The aim of
      this study is to evaluate the use of artificial neural network for nonendoscopic
      triage. METHODS: A cohort of 387 patients was used to train (n = 194) and
      internally validate (n = 193) the neural network, which was then externally
      validated in 200 patients and compared with the clinical and complete Rockall
      score. Two outcome variables were assessed: major stigmata of recent hemorrhage
      and need for endoscopic therapy. Patient cohort data from 2 independent tertiary
      care medical centers were prospectively collected. Adult patients hospitalized at
      both sites during the same time period with a primary diagnosis of acute
      nonvariceal UGIH. RESULTS: In predicting the 2 measured outcomes, sensitivity of
      neural network was >80%, with high negative predictive values (92-96%) in both
      cohorts but with lower specificity in the external cohort. Both Rockall scores
      had adequate sensitivity (>80%) but poor specificity (<40%) at outcome
      prediction. Comparing areas under receiver operating characteristic curves, the
      clinical Rockall score was significantly inferior to neural network in both
      cohorts (</=0.65 vs. >/= 0.78), while in the external cohort, neural network
      performed similarly to the complete Rockall score (>/= 0.78). CONCLUSIONS: In
      acute nonvariceal UGIH, artificial neural network (nonendoscopic triage)
      performed as well as the complete Rockall score (endoscopic triage) at predicting
      stigmata of recent hemorrhage and need for endoscopic therapy, even when tested
      in an external patient population.

PMID- 18061182
TI  - Liver iron, HFE gene mutations, and hepatocellular carcinoma occurrence in
      patients with cirrhosis.
AB  - BACKGROUND & AIMS: The influence of HFE gene mutations and liver iron overload on
      hepatocellular carcinoma (HCC) occurrence in patients with cirrhosis is subjected
      to controversial results. The aim of this work was to clarify this influence in a
      large cohort of prospectively followed-up cirrhotic patients classified according
      to the cause of their liver disease. METHODS: Three hundred one consecutive
      cirrhotic patients (162 alcoholics and 139 HCV-infected patients) were included
      at time of diagnosis of cirrhosis and followed-up. Liver iron overload on initial
      biopsy according to modified Deugnier's score and C282Y/H63D HFE gene mutations
      were assessed. RESULTS: In patients with alcoholic cirrhosis (mean iron score,
      2.0 +/- 3.0; mean time of follow-up, 66.1 +/- 45.1 months), 40 (24.6%) developed
      HCC. Thirteen (8.02%) were heterozygotes for C282Y HFE gene mutation and had
      higher hepatic iron scores (3.6 +/- 3.8 vs 1.9 +/- 2.8, respectively, P = .05).
      In univariate analysis, liver iron overload as a continuous variable (HR, 1.23
      [1.13-1.34], P < .001) or in binary coding with an optimal threshold of iron
      score >/=2.0 (HR, 4.1 [2.1-7.3], P < .0001) and C282Y mutation carriage (HR, 2.7
      [1.2-6.3], P = .01) were risk factors for HCC. In multivariate analysis, liver
      iron and C282Y mutation carriage remained independent risk factors for HCC. In
      patients with HCV-related cirrhosis (C282Y mutation carriage, 17 [12.23%]; mean
      liver iron score, 0.9 +/- 1.9; mean time of follow-up, 85.5 +/- 42.1 months; HCC,
      63 [45.32%] patients), C282Y mutation carriage and liver iron were not associated
      with HCC occurrence. CONCLUSIONS: Liver iron overload and C282Y mutation are
      associated with a higher risk of HCC in patients with alcoholic but not HCV
      related cirrhosis.

PMID- 18061181
TI  - Validation and extension of the PREMM1,2 model in a population-based cohort of
      colorectal cancer patients.
AB  - BACKGROUND & AIMS: Early recognition of patients at risk for Lynch syndrome is
      critical but often difficult. Recently, a predictive algorithm-the PREMM(1,2)
      model-has been developed to quantify the risk of carrying a germline mutation in
      the mismatch repair (MMR) genes MLH1 and MSH2. However, the model's performance
      in an unselected, population-based colorectal cancer population as well as its
      performance in combination with tumor MMR testing are unknown. METHODS: We
      included all colorectal cancer cases from the EPICOLON study, a prospective,
      multicenter, population-based cohort (n = 1222). All patients underwent tumor
      microsatellite instability analysis and immunostaining for MLH1 and MSH2, and
      those with MMR deficiency (n = 91) underwent tumor BRAF V600E mutation analysis
      and MLH1/MSH2 germline testing. RESULTS: The PREMM(1,2) model with a >/=5% cut
      off had a sensitivity, specificity, and positive predictive value (PPV) of 100%,
      68%, and 2%, respectively. The use of a higher PREMM(1,2) cut-off provided a
      higher specificity and PPV, at expense of a lower sensitivity. The combination of
      a >/=5% cut-off with tumor MMR testing maintained 100% sensitivity with an
      increased specificity (97%) and PPV (21%). The PPV of a PREMM(1,2) score >/=20%
      alone (16%) approached the PPV obtained with PREMM(1,2) score >/=5% combined with
      tumor MMR testing. In addition, a PREMM(1,2) score of <5% was associated with a
      high likelihood of a BRAF V600E mutation. CONCLUSIONS: The PREMM(1,2) model is
      useful to identify MLH1/MSH2 mutation carriers among unselected colorectal cancer
      patients. Quantitative assessment of the genetic risk might be useful to decide
      on subsequent tumor MMR and germline testing.

PMID- 18061183
TI  - Estrogen regulation of the male reproductive tract in the frog, Rana esculenta: a
      role in Fra-1 activation in peritubular myoid cells and in sperm release.
AB  - Endogenous and environmental estrogens have been proved to affect male
      reproduction in vertebrates. Both positive and negative effects in the regulation
      of the reproductive tract have been described. Since it is well known that
      amphibians represent a useful model to study several aspects concerning
      reproductive activity, we have taken advantage of the frog, Rana esculenta, to
      study the involvement of estrogens in sperm release. We show here that pituitary
      hormones increased the number of peritubular myoid cells (PMCs) expressing Fra-1
      and induced testicular morphological changes related to sperm release. The
      estrogen antagonist ICI182-780 counteracted the hypophysis driven effects. In
      vivo and in vitro experiments demonstrated that 17beta-Estradiol acted directly
      on the testis to switch-on Fra-1 in PMCs. Furthermore, impairment of estrogen
      activity significantly reduced sperm release mainly affecting the detachment of
      spermatozoa from Sertoli cells (spermiation). Therefore, estrogens can be
      considered a new entry in the list of substances involved in spermiation.

PMID- 18061184
TI  - Sliding mode control with self-tuning law for uncertain nonlinear systems.
AB  - A robust sliding mode control that follows a self-tuning law for nonlinear
      systems possessing uncertain parameters is proposed. The adjustable control gain
      and a bipolar sigmoid function are on-line tuned to force the tracking error to
      approach zero. Control system stability is ensured using the Lyapunov method.
      Both simulation and experimental application of a planetary gear type inverted
      pendulum control system verify the effectiveness of the developed approach.

PMID- 18061185
TI  - Pathological fractures in primary bone sarcomas.
AB  - Pathological fractures in patients with primary bone sarcomas should not be
      considered an absolute indication for amputation. Initial fracture management
      should include cast immobilisation or external fixation avoiding tumour-cell
      dissemination. The extent of fracture displacement and the type of fracture
      stabilisation may affect the outcome of patients with primary bone sarcomas
      presenting with pathological fractures. Patients with high-grade primary bone
      sarcomas should be treated by neo-adjuvant chemotherapy, and limb-salvage
      surgery. Pathological fractures in chemo-resistant primary bone sarcomas are a
      relative contraindication for limb salvage surgery.

PMID- 18061186
TI  - How should one treat iatrogenic ulnar injury after closed reduction and
      percutaneous pinning of paediatric supracondylar humeral fractures?
AB  - OBJECTIVE: The purpose of this study was to assess iatrogenic ulnar nerve
      injuries after supracondylar humeral fractures treated with closed reduction and
      percutaneous pinning. METHODS: The series consisted of 473 children. All patients
      were treated with closed reduction and percutaneous pinning. Neurological
      examination performed immediately after the operation revealed 25 ulnar nerve
      injuries (5.2%) in patients who had completely normal neurological findings in
      the preoperative period. Electromyographic examinations were performed at 6 and
      12 weeks postoperatively in patient with ulnar nerve lesions. RESULTS: The mean
      age was 6 years (4-8 years). The mean hospitalisation time was 2 days and the
      mean follow-up time was 30.8 months (17-63 months). Twenty-two patients with
      electromyogram showed partial denervation and conduction blocks at the elbow at 6
      weeks. Regenerative electromyogram findings were found at 12 weeks. Sensory
      function in all patients had returned at a mean of 2 months (1-4 months) while
      motor function had returned at a mean of 5.4 months (1-7 months). Unusually all
      patients had complete return of nerve function and full motion in their elbows.
      CONCLUSION: We evaluated the results of 473 patients and to our knowledge this is
      the largest series in the literature. Although the rate of ulnar nerve injuries
      (5.2%) is comparable, the number of the patients (n: 22) is the largest in the
      literature and may allow us to draw stronger conclusions. In our opinion, if
      ulnar nerve injury is detected after the operation, patients should be followed
      up for 7 months without intervention.

PMID- 18061187
TI  - Treatment of deep partial thickness and indeterminate depth facial burn wounds
      with water-jet debridement and a biosynthetic dressing.
AB  - BACKGROUND: Debriding deep thermal injury to face and neck can be particularly
      challenging with cold knife techniques. Timely healing, a precondition for
      minimal scarring, is dependant upon optimal wound bed preparation. OBJECTIVE: A
      new water-jet surgical tool (Versajet) (Smith & Nephew, Hull, UK) has been
      designed for wound debridement. Ex vivo histologic analysis of depth of
      debridement on human skin confirmed that predictable and controlled depth of
      debridement could be obtained by adjusting apparatus settings. METHODS &
      MATERIALS: We prospectively studied the versatility of this instrument for the
      treatment of deep and indeterminate depth face and neck burns. Wounds were then
      covered with either a biosynthetic (Biobrane) (Bertek Pharmaceuticals Inc) or
      cultured biosynthetic dressing (TransCyte). RESULTS: Patient follow-up
      demonstrated no adverse effects. Placement of biosynthetic dressings was
      compatible with water-jet debridement. Median healing time for wounds covered
      with biosynthetic dressings was 14 days, and 12 days for those which received the
      cultured biosynthetic dressing. CONCLUSION: We have found the water-jet system to
      be a versatile instrument for surgical burn debridement with particular advantage
      in addressing the challenging and delicate contoured regions found in the face
      and neck. Accurate control of debridement depth facilitates wound bed preparation
      for simultaneous treatment with growth promoting biosynthetic dressings.

PMID- 18061188
TI  - Device related tangential excision in burns.
AB  - Tangential excision in burns serves to preserve uninjured tissue in order to
      maximise cosmesis and function. Excision of all necrotic tissue remains
      absolutely necessary prior to reconstruction, and the choice of debridement
      method will depend on the injury, the condition of the patient and the experience
      of the surgeon. A problem with tangential excision has been that the amount of
      tissue excised is often greater than the amount of necrotic tissue. Techniques of
      tangential excision are described. Those using a guard, such as the Goulian or
      Watson knife, allow the depth of the gap between the blade and the guard to be
      varied. However, there remains the issue of precision, and a variance between the
      shape of the blade and of certain parts of the body. "Shelving" can occur as
      variances in the depth of excision slopes conflict with the uniform thickness of
      split thickness grafts or Integra, and may lead to an excess of tissue at the
      periphery of a wound, or "stuck on" appearance. Dermatome debridement may result
      in less loss of tissue, but this technique can difficult to perform due to the
      amount of blood loss. The Versajet (Smith & Nephew, Hull, UK) hydrosurgery system
      enables a more precise removal of unhealthy tissue, as it allows the narrowest
      excision margin currently available. As with many new techniques, the debridement
      may take longer at first, but the improved results will justify the extra time.
      In addition to greater precision in tangential excision, a better and smoother
      surface for future grafting may be created.

PMID- 18061189
TI  - Early management of the mangled upper extremity.
AB  - Mangling injuries to the upper extremity can be devastating, and the early
      management of these injuries is critical for the success of the reconstruction.
      These are universally high energy injuries that will need to be taken to the
      operating room for effective management. Evaluation begins in the emergency
      department with assessment of vascularity, categorization of damaged structures
      and assessment of salvageability. There is no role for conservative treatment of
      these wounds, and once in the operating room, restoration of blood supply and
      adequate debridement are critical to the ultimate outcome. Removal of damaged,
      contaminated and devitalized tissues must occur. The goal of early treatment is
      to create a clean wound ready for reconstruction as soon as possible. Inadequate
      debridement will only delay reconstruction to the detriment of the patient.

PMID- 18061190
TI  - The systemic inflammatory response induced by trauma is reflected by multiple
      phenotypes of blood neutrophils.
AB  - Secondary morbidity and mortality after trauma are mainly due to a dysfunctional
      immune system. Severe injury can trigger a systemic inflammatory response, which
      is characterised by pre-activation or priming of neutrophils in peripheral blood.
      Signals initiated as result of local tissue damage can further activate these
      neutrophils leading to post-injury inflammatory complications. Additional trauma
      caused by surgical intervention can worsen the inflammatory response, thereby
      increasing the risk of these inflammatory complications. Limiting surgical
      procedures through damage control principles can reduce the risk of secondary
      morbidity. Inflammatory complications after injury cannot adequately be predicted
      using the current anatomical and physiological-based scoring systems. In this
      review we propose a methodology focussing on the activation state of the systemic
      inflammatory response with focus on neutrophils to aid in the risk assessment of
      secondary morbidity after trauma. Neutrophils are essential effector cells during
      the post-injury systemic inflammatory response. Neutrophils differentially
      express an array of surface receptors by which the cells can respond and adapt to
      changing environmental signals. The determination of specific expression profiles
      of neutrophil receptors can aid in phenotyping and quantifying the systemic
      inflammatory response. This article reviews the application of these specific
      signatures of neutrophil receptors as a consequence of severe injury.

PMID- 18061191
TI  - Spinal cord tumor mimicking obstetric brachial plexus palsy.

PMID- 18061192
TI  - Long-term outcomes in non-diabetic patients with metabolic syndrome undergoing
      revascularization for multi-vessel coronary artery disease.
AB  - AIM: The influence of metabolic syndrome (MS) on long-term mortality and
      morbidity in multi-vessel coronary artery disease (MV-CAD) is unclear. We studied
      the impact of MS on long-term outcomes in non-diabetic patients (NDM) with MV-CAD
      undergoing coronary revascularization in the Bypass Angioplasty Revascularization
      Investigation (BARI) trial and registry. METHODS: BARI trial and registry
      patients were separated into those with diabetes (DM) and those without. NDM
      fulfilling the NCEP definition of MS were identified. Ten year follow-up data
      were obtained on mortality, MI and development of diabetes. The data were
      analyzed using Cox proportional hazard modeling. RESULTS: In the BARI trial and
      registry 2962 NDM were identified. Of those, 510 patients had 3 or more
      components of the BARI-modified NCEP definition for MS, while 445 patients had 2
      components of the definition and were classified as the "mixed group". Compared
      to patients without MS, both MS group (RR=3.2, p<0.0001) and the mixed group
      (RR=1.9, p=0.02) had a higher incidence of DM over the 10-year follow-up. Type 2
      DM was found to be highly associated with 10-year mortality (RR=1.65, p<0.0001).
      However, there was no statistically significant difference in the rate of death
      or MI at 5 and 10 years between NDM with or without MS. In multivariate analysis,
      the presence of MS was not associated with 10-year mortality in the BARI
      population (RR=0.93, p=0.62). CONCLUSION: In this BARI follow-up study, we have
      affirmed the role of MS in predicting the development of diabetes in NDM at
      baseline. The 10-year risk of mortality and MI was not greater in NDM with MS who
      had MV-CAD and underwent revascularization, compared to patients without MS.
      Further studies to evaluate MS patients with MV-CAD undergoing coronary
      revascularization are warranted.

PMID- 18061193
TI  - Influence of race and sex on lipoprotein-associated phospholipase A2 levels:
      observations from the Dallas Heart Study.
AB  - AIMS: Most lipoprotein-associated phospholipase A2 (Lp-PLA2) studies included
      mainly white men. We sought to determine whether Lp-PLA2 levels differ according
      to race and sex. METHODS: Lp-PLA2 mass and activity were measured in 3332
      subjects age 30-65 participating in the Dallas Heart Study, a multiethnic,
      population-based, probability sample. Lp-PLA2 levels were compared between
      different race and sex groups. RESULTS: Mean age was 45+/-9 years and 44% were
      men; 30% were white, 17% hispanic, and 53% black. Mean Lp-PLA2 activity and mass
      were 146+/-40 nmol/min/mL and 191+/-60 ng/mL, respectively. Lp-PLA2 activity was
      lower in women compared with men (134+/-35 vs. 161+/-40, p=0.001) and was lowest
      in black (136+/-38), intermediate in hispanic (151+/-36), and highest in white
      subjects (161+/-39) (trend p=0.0001). In multivariable linear regression models,
      after adjusting for age, body mass index (BMI), smoking, total, low-density
      lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides
      and high sensitivity C-reactive protein (hsCRP), Lp-PLA2 activity was 19
      nmol/min/mL higher in men vs. women (p<0.001); compared with black subjects,
      adjusted Lp-PLA2 activity was 11 and 20 nmol/min/mL higher in white and hispanic
      subjects, respectively (both p<0.001). Similar race and sex differences were
      observed for Lp-PLA2 mass. CONCLUSION: Race and sex independently influence Lp
      PLA2 activity and mass. Thresholds to define Lp-PLA2 elevation may need to be sex
      and race specific.

PMID- 18061194
TI  - Polymorphisms in the peroxisome proliferator activated receptor alpha gene are
      associated with levels of apolipoprotein CIII and triglyceride in African
      Americans but not Caucasians.
AB  - BACKGROUND: We tested whether single nucleotide polymorphisms (SNPs) in the
      PPARalpha gene (PPARA) are associated with variations in levels of plasma
      apolipoprotein CIII (apoCIII) levels, as well as other lipids and lipoproteins,
      in African-Americans and Caucasians. METHODS AND RESULTS: We initially identified
      an intronic SNP (rs4253728) in PPARA that was associated with plasma apoCIII
      level (p<0.05) in a subset of 435 individuals from the total study population
      (n=944; 335 African-Americans and 609 Caucasians). This SNP was then genotyped in
      a second subset of 476 individuals (total 911 subjects with available data), and
      a previously described PPARA coding SNP (L162V) which was shown to be in moderate
      linkage disequilibrium with the intronic SNP (r(2)=0.18) was genotyped in 928
      subjects from the same study population. The minor allele frequencies for both
      SNPs were significantly lower in African-Americans compared with Caucasians (7.2%
      vs. 27.3% for rs4253728, 1.5% vs. 6.1% for L162V, both p<0.0001). African
      Americans had significantly lower levels of TG and apoCIII compared with
      Caucasians after adjusting for age, sex, body mass index (BMI), waist
      circumference and other baseline characteristics. However, racial differences in
      TG levels were attenuated after adjusting for apoCIII levels. The minor alleles
      for both PPARA SNPs were associated with higher TG and apoCIII levels. Race
      modified the associations of L162V with TG (p for interaction=0.0056) and apoCIII
      (p for interaction=0.0011). Levels of both TG and apoCIII were lower in African
      American but not Caucasian homozygotes for the major allele compared with
      carriers of the minor allele. Similar results were obtained for the intronic SNP,
      but the findings were no longer significant in a model that also contained L162V.
      CONCLUSIONS: Two PPARA SNPs, L162V and rs4253728 (intronic), are less prevalent
      in African-Americans than in Caucasians and in African-Americans only are
      associated with higher apoCIII and TG levels.

PMID- 18061196
TI  - An accurate finite element model of the cervical spine under quasi-static
      loading.
AB  - Cervical disc injury due to impact has been observed in clinical and
      biomechanical investigations; however, there is a lack of data that helps to
      elucidate the mechanisms of disc injury during these collisions. Therefore, it is
      necessary to understand the behavior of the cervical spine under different types
      of loading situations. A three dimensional finite element (FE) model for the
      multi-level cervical spine segment (C0-C7) was developed using computed
      tomography (CT) data and applied to study the internal stresses and strains of
      the intervertebral discs under quasi-static loading conditions. The
      intervertebral discs were treated as nonlinear, anisotropic and incompressible
      subjected to large deformations. The model accuracy was validated by comparing it
      with previously published experimental and numerical results for different
      movements. It was shown that the use of a fiber reinforced model to describe the
      behavior of the annulus of the discs would predict higher maximum shear strains
      than an isotropic one, being therefore important the use of complex constitutive
      models in order to be able to detect the appearance of injured zones, since those
      strains and stresses are supposed to be related with damage to soft tissues.
      Several movements were analyzed: flexion, extension and axial rotation, obtaining
      that the maximum shear stresses in the disc were higher for a flexo-extension
      movement.

PMID- 18061195
TI  - Mechanisms underlying recoupling of eNOS by HMG-CoA reductase inhibition in a rat
      model of streptozotocin-induced diabetes mellitus.
AB  - OBJECTIVE: HMG-CoA reductase inhibitors have been shown to upregulate GTP
      cyclohydrolase I (GTPCH-I), the key enzyme for tetrahydrobiopterin de novo
      synthesis and to normalize tetrahydrobiopterin levels in hyperglycemic
      endothelial cells. We sought to determine whether in vivo treatment with the HMG
      CoA reductase inhibitor atorvastatin is able to upregulate the GTPCH-I, to
      recouple eNOS and to normalize endothelial dysfunction in an experimental model
      of diabetes mellitus. METHODS AND RESULTS: In male Wistar rats, diabetes was
      induced by streptozotocin (STZ, 60 mg/kg). In STZ rats, atorvastatin feeding (20
      mg/kg/d, 7 weeks), normalized vascular dysfunction as analyzed by isometric
      tension studies, levels of circulating endothelial progenitor cells (FACS
      analysis), superoxide formation (assessed by lucigenin-enhanced chemiluminescence
      and dihydroethidium staining), vascular levels of the phosphorylated vasodilator
      stimulated phosphoprotein (P-VASP), tyrosine nitration of the prostacyclin
      synthase, expression of GTPCH-I, dihydrofolate reductase and eNOS, translocation
      of regulatory NADPH oxidase subunits rac1, p47phox and p67phox (assessed by
      Western blot) and vascular tetrahydrobiopterin levels as measured by HPLC.
      Dihydroethidine staining revealed that the reduction of vascular superoxide was
      at least in part due to eNOS recoupling. CONCLUSION: HMG-CoA reductase inhibition
      normalizes endothelial function and reduces oxidative stress in diabetes by
      inhibiting activation of the vascular NADPH oxidase and by preventing eNOS
      uncoupling due to an upregulation of the key enzyme of tetrahydrobiopterin
      synthesis, GTPCH-I.

PMID- 18061197
TI  - Toe-out gait in patients with knee osteoarthritis partially transforms external
      knee adduction moment into flexion moment during early stance phase of gait: a
      tri-planar kinetic mechanism.
AB  - Altered gait kinematics and kinetics are observed in patients with medial
      compartment knee osteoarthritis. Although various kinematic adaptations are
      proposed to be compensatory mechanisms that unload the knee, the nature of these
      mechanisms is presently unclear. We hypothesized that an increased toe-out angle
      during early stance phase of gait shifts load away from the knee medial
      compartment, quantified as the external adduction moment about the knee.
      Specifically, we hypothesized that by externally rotating the lower limb anatomy,
      primarily about the hip joint, toe-out gait alters the lengths of ground reaction
      force lever arms acting about the knee joint in the frontal and sagittal planes
      and transforms a portion of knee adduction moment into flexion moment. To test
      this hypothesis, gait data from 180 subjects diagnosed with medial compartment
      knee osteoarthritis were examined using two frames of reference. The first frame
      was attached to the tibia (reporting actual toe-out) and the second frame was
      attached to the laboratory (simulating no-toe-out). Four measures were compared
      within subjects in both frames of reference: the lengths of ground reaction force
      lever arms acting about the knee joint in the frontal and sagittal planes, and
      the adduction and flexion components of the external knee moment. The mean toe
      out angle was 11.4 degrees (S.D. 7.8 degrees , range -2.2 degrees to 28.4 degrees
      ). Toe-out resulted in significant reductions in the frontal plane lever arm (
      6.7%) and the adduction moment (-11.7%) in early stance phase when compared to
      the simulated no-toe-out values. These reductions were coincident with
      significant increases in the sagittal plane lever arm (+33.7%) and flexion moment
      (+25.0%). Peak adduction lever arm and moment were also reduced significantly in
      late stance phase (by -22.9% and -34.4%, respectively) without a corresponding
      increase in sagittal plane lever arm or flexion moment. These results indicate
      that toe-out gait in patients with medial compartment knee osteoarthritis
      transforms a portion of the adduction moment into flexion moment in early stance
      phase, suggesting that load is partially shifted away from the medial compartment
      to other structures.

PMID- 18061198
TI  - Application of parallel gradient high performance liquid chromatography with
      ultra-violet, evaporative light scattering and electrospray mass spectrometric
      detection for the quantitative quality control of the compound file to support
      pharmaceutical discovery.
AB  - The success of drug discovery assays, using plate-based technologies, relies
      heavily on the quality of the substrates being tested. Sample purity, identity
      and concentration must be assured for a screening hit to be validated. Most major
      pharmaceutical companies maintain large liquid screening files with often in
      excess of one million stock solutions, typically dissolved in DMSO. However, due
      to the inherent inaccuracies of high-throughput gravimetric analysis and
      automated dilution, stock solution concentrations can vary significantly from the
      assumed nominal value. Here, we present a rapid and effective method for
      measuring purity, identity and concentration of these stock solutions using four
      high-performance liquid chromatography (HPLC) columns with parallel ultraviolet
      spectrophotometry (UV), electrospray ionisation mass spectrometry (ESI-MS) and
      evaporative light scattering detection (ELSD) with a throughput of 1 min per
      sample.

PMID- 18061199
TI  - Analysis of glyphosate and aminomethylphosphonic acid by capillary
      electrophoresis with electrochemiluminescence detection.
AB  - A capillary electrophoresis (CE) method coupled with electrochemiluminescence
      (ECL) detection for the analysis of glyphosate (GLY) and its major metabolite
      aminomethylphosphonic acid (AMPA) is presented. Complete separation of GLY and
      AMPA was achieved in 8 min using a background electrolyte of 20 mM sodium
      phosphate (pH 9.0) and a separation voltage of 21 kV. ECL detection was performed
      with an indium tin oxide (ITO) working electrode bias at 1.6 V (vs. a Pt-wire
      reference) in a 30 0mM sodium phosphate buffer (pH 8.0) containing 3.5mM Ru(bpy)3
      2+ (where bpy=2.2'-bipyridyl). Linear correlation (r>or=0.997) between ECL
      intensity and analyte concentration was obtained in the ranges 0.169-16.9 and
      5.55-111 microg ml(-1) for GLY and AMPA, respectively. The limits of detection
      (LODs) for GLY and AMPA in water were 0.06 microg ml(-1) and 4.04 microg ml(-1),
      respectively. The developed method was applied to the analysis of GLY in
      soybeans. The LOD of GLY in soybean was 0.6 microg g(-1). Total analysis time
      including sample pretreatment was less than 1h.

PMID- 18061200
TI  - Electrophoretic mobility does not always reflect the charge on an oil droplet.
AB  - Electrophoresis is widely used to determine the electrostatic potential of
      colloidal particles. Oil droplets in pure water show negative or positive
      electrophoretic mobilities depending on the pH. This is commonly attributed to
      the adsorption of hydroxyl or hydronium ions, resulting in a negative or positive
      surface charge, respectively. This explanation, however, is not in agreement with
      the difference in isoelectric point and point of zero charge observed in
      experiment. Here we present molecular dynamics simulations of oil droplets in
      water in the presence of an external electric field but in the absence of any
      ions. The simulations reproduce the negative sign and the order of magnitude of
      the oil droplet mobilities at the point of zero charge in experiment. The
      electrostatic potential in the oil with respect to the water phase, induced by
      anisotropic dipole orientation in the interface, is positive. Our results suggest
      that electrophoretic mobility does not always reflect the net charge or
      electrostatic potential of a suspended liquid droplet and, thus, the
      interpretation of electrophoresis in terms of purely continuum effects may need
      to be reevaluated.

PMID- 18061201
TI  - Novel ionic liquid assisted synthesis of SnO2 microspheres.
AB  - Tin oxide (SnO2) microspheres with an average 2.5 microm in diameters have been
      successfully synthesized through a rapid hydrothermal process heating by
      microwave in the presence of an ionic liquid 1-butyl-3-methyl imidazolium
      tetrafluoroborate. X-ray diffraction, scanning electron microscopy and
      transmission electron microscopy are used to characterize the morphology and
      crystalline structure of the microspheres. The as-synthesized SnO2 microspheres
      exhibit a tetragonal rutile structure. The mechanism of the microspheres
      formation is proposed.

PMID- 18061202
TI  - Distribution and chemical coding of intramural neurons in the porcine ileum
      during proliferative enteropathy.
AB  - Enteric neurons are highly adaptive in their response to various pathological
      processes including inflammation, so the aim of this study was to describe the
      chemical coding of neurons in the ileal intramural ganglia in porcine
      proliferative enteropathy (PPE). Accordingly, juvenile Large White Polish pigs
      with clinically diagnosed Lawsonia intracellularis infection (PPE; n=3) and a
      group of uninfected controls (C; n=3) were studied. Ileal tissue from each animal
      was processed for dual-labelling immunofluorescence using antiserum specific for
      protein gene product 9.5 (PGP 9.5) in combination with antiserum to one of:
      vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin gene
      related peptide (CGRP), somatostatin (SOM), neuropeptide Y (NPY) or galanin
      (GAL). In infected pigs, enteric neurons were found in ganglia located within
      three intramural plexuses: inner submucosal (ISP), outer submucosal (OSP) and
      myenteric (MP). Immunofluorescence labelling revealed increases in the number of
      neurons containing GAL, SOM, VIP and CGRP in pigs with PPE. Neuropeptides may
      therefore have an important role in the function of porcine enteric local nerve
      circuits under pathological conditions, when the nervous system is stressed,
      challenged or afflicted by disease such as PPE. However, further studies are
      required to determine the exact physiological relevance of the observed adaptive
      changes.

PMID- 18061203
TI  - An optimized immunohistochemical method for detection of phosphorylated mitogen
      activated protein kinases.
AB  - Study of the in vivo spatio-temporal localization of modified proteins is likely
      to become a major focus of proteomics research in the near future. In this study
      we optimized and tested an immunohistochemical procedure for detecting unstable
      phosphorylated mitogen-activated protein (MAP) kinases. Using our method,
      phosphorylated MAP kinases can be sensitively and reproducibly localized in the
      developing white matter of murine spinal cord on embryonic day 15. Our method is
      simple and effective, and so may be useful in future proteomics research.

PMID- 18061205
TI  - The three-dimensional structure of VIM-2, a Zn-beta-lactamase from Pseudomonas
      aeruginosa in its reduced and oxidised form.
AB  - The crystal structures of the universally widespread metallo-beta-lactamase (MBL)
      Verona integron-encoded MBL (VIM)-2 from Pseudomonas aeruginosa have been solved
      in their native form as well as in an unexpected oxidised form. This carbapenem
      hydrolysing enzyme belongs to the so-called B1 subfamily of MBLs and shares the
      folding of alpha beta/beta alpha sandwich, consisting of a core of beta-sheet
      surrounded by alpha-helices. Surprisingly, it showed a high tendency to be
      strongly oxidised at the catalytic cysteine located in the Cys site, Cys221,
      which, in the oxidised structure, becomes a cysteinesulfonic residue. Its native
      structure was obtained only in the presence of Tris(2-carboxyethyl)phosphine.
      This oxidation might be a consequence of a lower affinity for the second Zn
      located in the Cys site that would also explain the observed susceptibility of
      VIM-2 to chelating agents. This modification, if present in nature, might play a
      role in catalytic down-regulation. Comparison between native and oxidised VIM-2
      and a predicted model of VIM-1 (which shows one residue different in the Cys site
      compared with VIM-2) is performed to explain the different activities and
      antibiotic specificities.

PMID- 18061206
TI  - Development and evaluation of the Daily Assessment of Symptoms - Anxiety (DAS-A)
      scale to evaluate onset of symptom relief in patients with generalized anxiety
      disorder.
AB  - BACKGROUND: Fast-acting anxiolytics are important to patients and society.
      Measuring early onset, however, requires a sensitive and clinically responsive
      measure. This study develops and evaluates the psychometric properties of a new
      patient-reported instrument, the Daily Assessment of Symptoms - Anxiety (DAS-A),
      designed to detect reduction of anxiety symptoms in patients with Generalized
      Anxiety Disorder (GAD) during the first week of treatment. METHODS: Clinician
      interviews and patient focus groups were conducted to identify relevant
      constructs; discussions focused on early symptom improvement and meaningful
      changes in GAD symptoms. The draft questionnaire underwent iterative sets of
      cognitive interviews to inform item reduction and revision. A double-blind,
      randomized, placebo-controlled study of paroxetine and lorazepam assessed the
      performance of the new instrument in GAD patients. Analyses evaluated the
      structure, reliability, validity, and utility of the instrument. RESULTS: There
      was consistency across focus groups and clinicians in the description of symptoms
      that improve first. The final item set was easily understood by interview
      participants. Factor analyses indicated that a unidimensional structure best
      described the data. Item-level descriptive statistics, Cronbach's alphas, effect
      sizes, and validity correlations with other scales were favorable. Most
      importantly, the DAS-A demonstrated separation of lorazepam from placebo within
      24h of first dose and correlated with other anxiety measures. CONCLUSIONS: This
      study resulted in the development of a reliable and valid instrument addressing
      the DSM-IV dimensions of GAD. The DAS-A is capable of detecting reduction in
      anxiety symptoms within 24h, making it a desirable measure to include in future
      trials of fast-acting anxiety medications.

PMID- 18061204
TI  - Mechanisms and potential therapeutic targets for ventricular arrhythmias
      associated with impaired cardiac calcium cycling.
AB  - The close relationship between life-threatening ventricular arrhythmias and
      contractile dysfunction in the heart implicates intracellular calcium cycling as
      an important underlying mechanism of arrhythmogenesis. Despite this close
      association, however, the mechanisms of arrhythmogenesis attributable to impaired
      calcium cycling are not fully appreciated or understood. In this report we review
      some of the current thinking regarding arrhythmia mechanisms associated with
      either abnormal impulse initiation (i.e. arrhythmia triggers) or impulse
      propagation (i.e. arrhythmia substrates). In all cases, the mechanisms are
      primarily related to dysfunction of calcium regulatory proteins associated with
      the sarcomere. These findings highlight the broad scope of arrhythmias associated
      with abnormal calcium cycling, and provide a basis for a causal relationship
      between cardiac electrical instability and contractile dysfunction. Moreover,
      calcium cycling proteins may provide much needed targets for novel antiarrhythmic
      therapies.

PMID- 18061207
TI  - Occlusive vessel signs on MRI as only findings of hyperacute ischemic stroke.
AB  - A 64-year-old woman presented with a partial seizure on the left side of her
      face. Although diffusion weighted images and magnetic resonance angiography 3 h
      after the onset did not show any signs of ischemic stroke, a susceptibility
      vessel sign (SVS) on T2*-weighted gradient echo imaging (GRE) and a hyperintense
      vessel sign (HVS) on fluid attenuated inversion recovery images at the distal
      branch of the right middle cerebral artery were revealed. One day later, these
      GRE SVS and HVS signs disappeared and a new infarct lesion in the right insular
      cortex was found on magnetic resonance images (MRI). It is suggested that
      occlusive vessel signs on MRI, including GRE SVS and HVS, are sometimes the only
      findings of ischemic stroke at the hyperacute phase.

PMID- 18061208
TI  - A case of ovarioleukodystrophy without eIF2B mutations.
AB  - A new association of Vanishing White Matter (VWM) and premature ovarian failure
      (POF) was recently described as a sole entity called ovarioleukodystrophy. Seven
      out of eight patients reported by Fogli et al. had translation initiation factor
      (eIF2B) mutations, specific to the VWM. The only patient without mutations had a
      distinctive neurological presentation that included cognitive deterioration
      without motor signs and white matter abnormalities restricted to the frontal
      lobe. We describe here a case suggestive of ovarioleukodistrophy carrying no
      eIF2B mutations.

PMID- 18061209
TI  - The direct action of estrone on vascular tissue involves genomic and non-genomic
      actions.
AB  - A two step model mechanism of steroid action has been recently postulated. In
      this study, we test the hypothesis that, the biochemical action of estrone (E(1))
      on vascular tissue could be performed via genomic and non-genomic actions. Rat
      aortic rings or vascular smooth muscle cell cultures (VSMC) were used to test the
      effect of the hormone on nitric oxide (NO) production, protein kinases activities
      and cell proliferation. Our data showed that estrone increased NO synthesis
      between 30 s and 20 min treatment, and this stimulatory effect was dependent on
      MAPK cascade activation, since it was prevented in the presence of a MAPK
      inhibitor (PD98059). Using a phosphorylation assay, we also showed that E(1)
      significantly increased MAPK activity. The effect of the hormone on PKC activity
      was measured in concentrations and time course studies. Direct treatment of rat
      aortic homogenates with E(1) significantly enhanced PKC activity (1-10 fold
      increase, p<0.01) at all concentrations (1; 10; 50 nM) and time tested (1-10
      min). We demonstrated that 24 h of E(1) treatment markedly increased VSMC
      proliferation (53% above control), and this effect was suppressed by a PKC
      inhibitor. The rapid and the long term effects of the hormone were completely
      suppressed in the presence of an estradiol receptor antagonist (ICI 182780). In
      summary, we provided evidence that, the steroid exerts both non-genomic and
      genomic actions, the former associated with MAPK kinase dependent on NO
      production, and the latter related with induction of VSMC proliferation involving
      PKC pathway activation.

PMID- 18061210
TI  - A report card and quality indicators for the Seine estuary: from scientific
      approach to operational tool.
AB  - The scientific teams from the interdisciplinary Seine-Aval (SA) research program
      and the SA's operational pole, GIPSA (Groupement d'Interet Public Seine-Aval)
      have worked together to create a report card designed to help the Estuary Council
      (Conseil de l'Estuaire) revitalize its original functions: maintaining functional
      links between the various estuarine ecosystems, comprehending and managing the
      estuary's natural habitats and biological populations, and monitoring and
      improving the physical-chemical quality of the estuarine waters. The report card
      will be able to synthesize the information obtained from several system
      performance variables and available operational indicators. This approach,
      intended to guide the estuary managers, is the oeuvre of several scientific
      teams; it is particularly important in the context of the Water Framework
      Directive because it facilitates the elaboration of a group of relevant
      indicators, which can then be used as operational tools. A report card will
      provide decision-makers (e.g., political authorities; national, regional and
      local institutions and industries) with the key indicators for evaluating the
      system and predicting changes in terms of selected objectives, such as the
      preservation and restoration of the estuary's environmental functionalities. The
      final objective of the research is to choose among the available indicators to
      approximate potential ecological risks. Integrating the socio-economical data
      will perhaps lead to setting risk acceptability thresholds for the different uses
      of the Seine estuary. In the end, collaboration between the scientists, the
      managers, and the GIPSA operational pole will be essential to produce a viable
      report card about the environmental status of the Seine estuary. To illustrate
      the research now under way, this article presents the results for three actions
      undertaken, concerning: (i) physical indicators (i.e., an inventory of the
      estuary first as a whole, and then section by section); (ii) benthic indicators
      (i.e., seven indices which show a moderate EcoQ for the lower part of the
      estuary); and (iii) a eutrophication indicator (i.e., an indicator for coastal
      eutrophication potential (ICEP), which helps to limit the nutrient fluxes (N or
      P) that exceed the silica flux delivered by the Seine network, based on the
      Redfield ratios for algal propagation).

PMID- 18061211
TI  - Genetic impact of the Prestige oil spill in wild populations of a poor dispersal
      marine snail from intertidal rocky shores.
AB  - In November 2002, the sinking of the Prestige cargo ship produced an oil spill of
      60,000 tons that affected many areas along the Galician coast (in the northwest
      of Spain). In a number of rocky shore sites, most organisms (particularly marine
      mollusks) were nearly extinct at a local scale. We tested whether the local
      bottleneck/extinction that occurred in affected localities caused any detectable
      reduction of the genetic diversity in the marine snail Littorina saxatilis, an
      ovoviviparous rocky shore model species characterized by a low dispersal ability,
      high population density, and wide distribution range. We compared the level of
      genetic variation and population differentiation between affected (polluted) and
      control sites located in seven geographical areas (three sites per area, one
      impacted and two controls, and two replicates per site) one and a half years
      after the spill. The analysis included molecular marker variation (microsatellite
      and AFLP loci) and quantitative trait genetic variation for shell variables in
      embryos extracted from pregnant females. Our results indicate that the affected
      populations did not show a significant overall reduction in genetic diversity
      when compared to the controls, suggesting that the species is highly resistant to
      losing genetic variability as a consequence of a local short-term pollution
      process in spite of its low dispersal ability and direct development. However,
      some genetic effects were detected in the polluted populations, particularly for
      quantitative shell traits and AFLPs, consistent with local adaptations resulting
      from the fuel contamination.

PMID- 18061212
TI  - The main characteristics, problems, and prospects for Western European coastal
      seas.
AB  - Located to the far West of Western Europe, France has a western maritime coastal
      zone of more than 3800 km, which is widely influenced by the North-eastern
      Atlantic. The English Channel, an epi-continental shallow sea with very strong
      tides, runs along 650 km of the French coast and 1100 km of the English coast. It
      is also a bio-geographical crossroad encompassing a much wider range of
      ecological conditions than other European seas. France's Atlantic coast north of
      the Gironde estuary is a succession of rocky and sandy shorelines, including a
      sizeable intertidal zone, a wide continental shelf, and two major estuaries
      (Loire and Gironde). South of the Gironde, the 260 km of coastline is low, sandy
      and straight, with a narrowing continental shelf further on South due to the
      presence of the Cape Breton canyon in the bathyal and abyssal zones. Interface
      between the continental and oceanic systems, these bordering seas--North Sea,
      English Channel and Atlantic Ocean--have been the subject of many recent research
      programmes (the European Mast-FLUXMANCHE and INTERREG programmes; the national
      coastal environment programme and the LITEAU programme in France), designed to
      improve comprehension of the functions, production, and dynamics of these seas as
      well as their future evolution. Given the many conflicting practices in these
      littoral zones, integrated coastal zone management appears to be essential in
      order to cope with both natural phenomena, such as the infilling of estuarine
      zones, cliff erosion, and rising sea levels, and chronic anthropogenic pressures,
      such as new harbour installations (container dikes, marinas), sea aggregate
      extraction for human constructions, and offshore wind mill farms. This article
      provides as complete an overview as possible of the research projects on these
      bordering seas, both those that have recently been accomplished and those that
      are currently in progress, in order to highlight the main characteristics of
      these ecosystems and to underline the future challenges for European marine
      research in terms of the integrated coastal zone management of these highly
      significant coastal zones.

PMID- 18061213
TI  - [Osteosarcoma of the skull base: a case report].
AB  - Osteosarcoma, usually observed in long bones, is the second most frequent
      primitive malignant bone tumor after myeloma. The skull base is an exceptional
      localization. We report a case of skull base osteosarcoma managed in our
      department. A 23-year-old female was admitted for bilateral epistaxis, headache,
      decreasing visual acuity then blindness. Physical examination revealed bilateral
      blindness and exophthalmia. Cranial magnetic resonance imaging showed a
      voluminous mass in the skull base extending to the nasosinusal area. A
      rhinoseptal surgical approach was used but the tumor was so huge that excision
      was impossible. The biopsy identified at an osteoblastic osteosarcoma. Search for
      extension (chest computed tomography and abdominal ultrasonography) was negative.
      Chemotherapy was to be delivered before combination chemoradiotherapy but the
      patient died before any treatment could be started. Osteosarcoma of the skull
      base is very rare. The treatment is based on surgery which should be as complete
      as possible followed by chemoradiotherapy. Prognosis is poor. Median survival is
      around six months.

PMID- 18061214
TI  - [Subthalamic nucleus stimulation using a Fisher ZD stereotactic frame, MR-CT
      fusion guidance and peroperative orthogonal radiographs, in Parkinson disease].
AB  - BACKGROUND: We present the method and results of an original technique to implant
      electrodes in the subthalamic nucleus (STN) to treat Parkinson's disease, based
      on adaptations of the Fisher ZD stereotactic frame. METHODS: Targets coordinates
      were calculated after fusion of stereotactic CT-scan and MRI images. STN was
      localized by its theoretical coordinates according to AC-PC and by its direct
      visualization on T2 images. Electrodes were implanted after local anesthesia,
      using peroperative multicanal microrecordings and test stimulation. Electrodes
      location was checked by peroperative perpendicular radiographs. To avoid
      projection of the frame arm on the area of interest on anteroposterior and
      lateral radiographs, the arm was fixed at 45 degrees from the usual 90 degrees
      position. This original fixation needed a trigonometric transformation of the X
      and Y stereotactic coordinates. Radiopaque markers, fixed on the frame, were
      identified on the radiographs, allowing the calculation of the stereotactic
      coordinates of the electrode tip, which were then entered in the stereotactic
      MRI, to check its location from the defined target. RESULTS: No problem due to
      adaptations of the frame occurred in the 60 patients. In all cases, peroperative
      radiographs allowed to confirm the correct location of electrodes. Six months
      after surgery, UPDRS III score without medication was decreased by 52% with
      stimulation "on". UPDRS IV items 32, 33 and 39 scores were decreased by 75,7,
      79,5 and 72%. Daily dopa-equivalent dose was decreased by 71%. One asymptomatic
      thalamic hematoma and two wound infections occurred. CONCLUSION: This method was
      efficient and safe to implant deep electrodes.

PMID- 18061215
TI  - Behavioral characterization of mice deficient in the phosphodiesterase-10A
      (PDE10A) enzyme on a C57/Bl6N congenic background.
AB  - The phenotype of genetically modified animals is strongly influenced by both the
      genetic background of the animal as well as environmental factors. We have
      previously reported the behavioral and neurochemical characterization of PDE10A
      knockout mice maintained on a DBA1LacJ (PDE10A(DBA)) genetic background. The aim
      of the present studies was to assess the behavioral and neurochemical phenotype
      of PDE10A knockout mice on an alternative congenic C57BL/6N (PDE10A(C57)) genetic
      background. Consistent with our previous results, PDE10A(C57) knockout mice
      showed a decrease in exploratory locomotor activity and a delay in the
      acquisition of conditioned avoidance responding. Also consistent with previous
      studies, the elimination of PDE10A did not alter basal levels of striatal cGMP or
      cAMP or affect behavior in several other well-characterized behavioral assays.
      PDE10A(C57) knockout mice showed a blunted response to MK-801, although to a
      lesser degree than previously observed in the PDE10A(DBA) knockout mice, and no
      differences were observed following a PCP challenge. PDE10A(C57) knockout mice
      showed a significant change in striatal dopamine turnover, which was accompanied
      by an enhanced locomotor response to AMPH, These studies demonstrate that while
      many of the behavioral effects of the PDE10A gene deletion appear to be
      independent of genetic background, the impact of the deletion on behavior can
      vary in magnitude. Furthermore, the effects on the dopaminergic system appear to
      be background-dependent, with significant effects observed only in knockout mice
      on the C57BL6N genetic background.

PMID- 18061217
TI  - Huntington's disease impairs recognition of angry and instrumental body language.
AB  - Patients with Huntington's disease (HD) exhibit motor impairments as well as
      cognitive and emotional deficits. So far impairments in the ability to recognize
      emotional stimuli have mostly been investigated by using facial expressions and
      emotional voices. Other important emotional signals are provided by the whole
      body. To investigate the impact of motor deficits on body recognition and the
      relation between motor disorders and emotion perception deficits, we tested
      recognition of emotional body language (instrumental, angry, fearful and sad) in
      19 HD patients and their matched controls with a nonverbal whole body expression
      matching task. Results indicate that HD patients are impaired in recognizing both
      instrumental and angry whole body postures. Furthermore, the body language
      perception deficits are correlated with measures of motor deficit. Taken together
      the results suggest a close relationship between emotion recognition
      (specifically anger) and motor abilities.

PMID- 18061218
TI  - Varied effects of conventional antiepileptics on responding maintained by
      negative versus positive reinforcement.
AB  - We analyzed the effects of four conventional antiepileptic drugs (AEDs) -
      carbamazepine (CBZ), ethosuximide (ETH), phenytoin (PHT), and valproate (VPA) -
      on operant behavior maintained by negative or positive reinforcement
      contingencies. Rats were trained to lever press on a free-operant avoidance
      schedule or variable-interval (VI) schedule of appetitive reinforcement. Dose
      effect functions were separately established on each reinforcement contingency
      for CBZ (12.5-100 mg/kg), ETH (25-200 mg/kg), PHT (12.5-50 mg/kg), and VPA (50
      400 mg/kg). CBZ and PHT reduced responding on free-operant avoidance and VI
      appetitive reinforcement tasks, with positively reinforced behavior reduced at
      lower drug dosages than negatively reinforced responding. ETH and VPA reduced
      responding on the VI appetitive reinforcement task, but did not alter behavior
      maintained on the free-operant avoidance schedule. Our results suggest that
      conventional AEDs vary in their effect on operant behavior, depending on the type
      of reinforcement process maintaining responding.

PMID- 18061219
TI  - Enhancement of the acoustic startle reflex by an alarm pheromone in male rats.
AB  - Recently, we reported that an alarm pheromone released from the perianal region
      of male rats aggravated stress-induced hyperthermia and increased defensive and
      risk assessment behaviors in recipient male rats. Based on these results, we
      hypothesized that the primary effect of the alarm pheromone is to increase
      anxiety; however, there is still no clear evidence for this pheromone effect.
      Therefore, we examined this issue by assessing the effect of the alarm pheromone
      on the acoustic startle reflex (ASR), which is a useful index for studying
      negative emotions such as anxiety in rats. The alarm pheromone enhanced the ASR
      for 105-dB auditory stimuli, but not for those of 90 and 120 dB, when these three
      intensities of sound were used randomly. The same results were obtained when one
      of these three intensities was used repeatedly. In addition, pretreatment with
      diazepam (i.p.) at doses of 0.7 and 2.0 mg/kg suppressed the ASR of the pheromone
      recipients, whereas the lower dose (0.2 mg/kg) slightly attenuated the pheromone
      effect and the control injection (vehicle) had no effect. These results indicate
      that the alarm pheromone enhances the ASR by increasing anxiety in recipient
      rats, suggesting that the primary effect of the alarm pheromone is to increase
      the anxiety level.

PMID- 18061220
TI  - 21beta-Hydroxy-oleanane-type triterpenes from Hippocratea excelsa.
AB  - Stem bark of Hippocratea excelsa afforded six pentacyclic triterpenes, five
      oleanane and one ursane types. They were identified as 11beta,21beta-dihydroxy
      olean-12-ene-3-one (2), 3alpha,11alpha,21beta-trihydroxy-olean-12-ene (3),
      3alpha,21beta-dihydroxy-11alpha-methoxy-olean-12-ene (4), 3alpha,21beta-dihydroxy
      olean-9(11),12-diene (5), 3alpha,21beta-dihydroxy-olean-12-ene (6) and
      3alpha,21beta-dihydroxy-11alpha-methoxy-urs-12-ene, isolated as its diacetate
      derivative (7), as well as 3alpha,21beta-dihydroxy-olean-12-ene (1) previously
      isolated from the root bark. The known alpha- and beta-amyrin, oleanoic and
      ursolic acids, trans-polyisoprene, and the ubiquitous beta-sitosterol were also
      isolated. Structures were elucidated on the basis of spectroscopic analyses,
      including homo- and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC
      and HMBC) and comparison with literature data. The antigiardial activity of
      compounds 2-5 was not significant.

PMID- 18061221
TI  - Withanolides from Withania somnifera roots.
AB  - Two new and seven known withanolides along with beta-sitosterol, stigmasterol,
      beta-sitosterol glucoside, stigmasterol glucoside, alpha+beta glucose were
      isolated from the roots of Withania somnifera. Among the known compounds, Viscosa
      lactone B, stigmasterol, stigmasterol glucoside and alpha+beta glucose are being
      reported from the roots of W. somnifera for the first time. One of the new
      compounds contained the rare 16beta-acetoxy-17(20)-ene the other contained
      unusual 6alpha-hydroxy-5,7alpha-epoxy functional groups in the withasteroid
      skeleton. The structures were elucidated by spectroscopic methods and chemical
      transformations.

PMID- 18061222
TI  - Taking the long view.

PMID- 18061223
TI  - Brain monitoring in dogs using the cerebral state index during the induction of
      anaesthesia via target-controlled infusion of propofol.
AB  - The aim of this study was to evaluate the correlation between the cerebral state
      index (CSI) and the estimated propofol plasma concentrations in dogs during
      induction of anaesthesia. Fifteen healthy dogs undergoing scheduled routine
      surgical procedures were enrolled in this study. Target controlled infusion (TCI)
      software, based on the pharmacokinetic model for propofol, was used to control
      the syringe pump and to estimate plasma propofol concentrations (PropCp) and the
      CSI values every five-seconds. Three electrodes placed in the centre of the
      forehead, on the left side of the forehead and on the left mastoid were used to
      collect the electroencephalographic (EEG) signal converted by the cerebral state
      monitor into the CSI. The cerebral electrical changes induced by increasing
      propofol concentrations appear to be detected by CSI monitoring in dogs. The
      negative correlation between CSI and PropCp demonstrates that the CSI could be
      used to assess electrical brain activity in dogs during the induction of
      anaesthesia with propofol.

PMID- 18061224
TI  - Seroprevalence of Taenia solium antibodies in Vellore district, south India.
AB  - Although Taenia solium neurocysticercosis is the cause of almost one-third of
      epilepsy in Vellore district, south India, the level of exposure to T. solium in
      the district is not known. This study determined the seroprevalence of
      cysticercus antibodies in seizure-free, study subjects aged 2-60 years from urban
      and rural areas of Vellore district. Cysticercus antibodies, as determined by
      immunoblots, were noted in 15.9% of 1063 people and were significantly higher in
      the rural population (17.7%) compared with the urban population (6.0%). Twenty
      four percent of the rural population and 12% of the urban population ate pork.
      One-third of all households in the district had one or more members seropositive
      for cysticercus antibodies. The high index of exposure to T. solium in south
      India calls for improved animal husbandry and sanitation.

PMID- 18061225
TI  - Selective reactivity of 2-mercaptoethanol with 5beta,6beta-epoxide in steroids
      from Withania somnifera.
AB  - 2-Mercaptoethanol reacts selectively with the 5beta,6beta-epoxy steroids isolated
      from Withania somnifera substituting the epoxide by a six-membered oxyethylene-2'
      thio ring whereas it failed to show such reactivity on 6alpha,7alpha-epoxy
      withasteroids. The structure of the product has been elucidated by spectroscopic
      methods, especially applying extensive 2D NMR methods. The anticancer activity of
      withaferin A was lost in the reaction product indicating that its activity is
      also linked to the free 5beta,6beta-epoxide functional group.

PMID- 18061226
TI  - Ammonium-induced calcium mobilization in 1321N1 astrocytoma cells.
AB  - High blood levels of ammonium/ammonia (NH(4)(+)/NH(3)) are associated with severe
      neurotoxicity as observed in hepatic encephalopathy (HE). Astrocytes are the main
      targets of ammonium toxicity, while neuronal cells are less vulnerable. In the
      present study, an astrocytoma cell line 1321N1 and a neuroblastoma glioma hybrid
      cell line NG108-15 were used as model systems for astrocytes and neuronal cells,
      respectively. Ammonium salts evoked a transient increase in intracellular calcium
      concentrations ([Ca(2+)](i)) in astrocytoma (EC(50)=6.38 mM), but not in NG108-15
      cells. The ammonium-induced increase in [Ca(2+)](i) was due to an intracellular
      effect of NH(4)(+)/NH(3) and was independent of extracellular calcium. Acetate
      completely inhibited the ammonium effect. Ammonium potently reduced calcium
      signaling by G(q) protein-coupled receptors (H(1) and M3) expressed on the cells.
      Ammonium (5 mM) also significantly inhibited the proliferation of 1321N1
      astrocytoma cells. While mRNA for the mammalian ammonium transporters RhBG and
      RhCG could not be detected in 1321N1 astrocytoma cells, both transporters were
      expressed in NG108-15 cells. RhBG and RhBC in brain may promote the excretion of
      NH(3)/NH(4)(+) from neuronal cells. Cellular uptake of NH(4)(+)/NH(3) was mainly
      by passive diffusion of NH(3). Human 1321N1 astrocytoma cells appear to be an
      excellent, easily accessible human model for studying HE, which can substitute
      animal studies, while NG108-15 cells may be useful for investigating the role of
      the recently discovered Rhesus family type ammonium transporters in neuronal
      cells. Our findings may contribute to the understanding of pathologic ammonium
      effects in different brain cells, and to the treatment of hyperammonemia.

PMID- 18061227
TI  - Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint
      venture" alkaloid from arthropods and amphibians.
AB  - Certain amphibians provide themselves with a chemical defense by accumulating
      lipophilic alkaloids into skin glands from dietary arthropods. Examples of such
      alkaloids are pumiliotoxins (PTXs). In general, PTXs are known as positive
      modulators of voltage-gated sodium channels (VGSCs). Unlike other PTXs, PTX 251D
      does not share this characteristic. However, mice and insect studies showed that
      PTX 251D is highly toxic and to date the basis of its toxicity remains unknown.
      In this work, we searched for the possible target of PTX 251D. The toxin was
      therefore made synthetically and tested on four VGSCs (mammalian
      rNa(v)1.2/beta(1), rNa(v)1.4/beta(1), hNa(v)1.5/beta(1) and insect Para/tipE) and
      five voltage-gated potassium channels (VGPCs) (mammalian rK(v)1.1-1.2, hK(v)1.3,
      hK(v)11.1 (hERG) and insect Shaker IR) expressed heterologously in Xenopus laevis
      oocytes, using the two-electrode voltage clamp technique. PTX 251D not only
      inhibited the Na(+) influx through the mammalian VGSCs but also affected the
      steady-state activation and inactivation. Interestingly, in the insect ortholog,
      the inactivation process was dramatically affected. Additionally, PTX 251D
      inhibited the K(+) efflux through all five tested VGPCs and slowed down the
      deactivation kinetics of the mammalian VGPCs. hK(v)1.3 was the most sensitive
      channel, with an IC(50) value 10.8+/-0.5 microM. To the best of our knowledge
      this is the first report of a PTX affecting VGPCs.

PMID- 18061228
TI  - Focusing the immune response on the V3 loop, a neutralizing epitope of the HIV-1
      gp120 envelope.
AB  - Rabbits were immunized with a novel regimen designed to focus the immune response
      on a single neutralizing epitope of HIV-1 gp120 and thereby preferentially induce
      neutralizing antibodies (Abs). Animals were primed with gp120 DNA from a clade A
      Env bearing the GPGR V3 motif and/or a clade C Env bearing the GPGQ V3 motif, and
      boosted with one or more fusion proteins containing V3 sequences from clades A, B
      and/or C. Immune sera neutralized three of four Tier 1 primary isolates,
      including strains heterologous to the immunizing strains, and potent cross-clade
      neutralizing activity was demonstrated against V3 chimeric pseudoviruses carrying
      in a Tier 1 Env, the consensus V3 sequences from clades A1, AG, B, AE, or F. The
      broadest and most potent neutralizing responses were elicited with the clade C
      gp120 DNA and a combination of V3-fusion proteins from clades A, B and C.
      Neutralizing activity was primarily due to V3-specific Abs. The results
      demonstrate that the immune response can be focused on a neutralizing epitope and
      show that the anti-V3 Abs induced recognize a diverse set of V3 loops.

PMID- 18061229
TI  - Co-replication analyses of naturally occurring defective hepatitis B virus
      variants with wild-type.
AB  - Complex hepatitis B virus (HBV) variants with mutations in core promoter (Cp)
      plus deletions in the C gene and/or preS region--that are associated with
      development of liver cirrhosis in renal transplant recipients--show a drastically
      changed phenotype with altered transcription and disturbed surface and core
      protein expression. Here, we analyzed the replication phenotype of six different
      defective variant genomes, isolated from two patients, after co-transfection with
      HBV wild-type (wt) in varying proportions. Both in HuH7 and HepG2 cells, the
      variants showed enhanced replication and enrichment in the different transfected
      variant-wt mixtures. Contrary to artificial variants with only C gene deletions
      in wt context, the original complex variants as well as wt genomes carrying C
      gene and Cp mutations of the variants did mostly not suppress wt replication.
      Thus, the Cp mutations compensate the suppression of wt by C gene deletions and
      furthermore enhance the replication level.

PMID- 18061230
TI  - Endomembranes and myosin mediate assembly into tubules of Pns10 of Rice dwarf
      virus and intercellular spreading of the virus in cultured insect vector cells.
AB  - Rice dwarf virus (RDV) spreads, along actin-based filopodia, as one of the ways
      of its transport, from infected to non-infected cells of its vector insect via
      tubules that are composed of the viral nonstructural protein Pns10 and contain
      viral particles. An inhibitor that perturbs the endomembrane system, namely,
      brefeldin A, and butanedione monoxime, an inhibitor of myosin motor activity,
      abolished the formation of such tubules, preventing the direct cell-to-cell
      spread of RDV without any significant effects on the production of viral
      particles. The microtubule-depolymerizing drug NOC, which had a negligible effect
      on the formation and protrusion of such tubules from cells, did not inhibit the
      intercellular spread of RDV. Our observations suggest that the endomembrane
      system and myosin motors, but not microtubule, are required for the Pns10 tubule
      formation and are, therefore, involved in the secondary infection by RDV of
      adjacent cells.

PMID- 18061231
TI  - Comparative evaluation of trimeric envelope glycoproteins derived from subtype C
      and B HIV-1 R5 isolates.
AB  - We previously reported that an envelope (Env) glycoprotein immunogen (o
      gp140DeltaV2SF162) containing a partial deletion in the second variable loop (V2)
      derived from the R5-tropic HIV-1 isolate SF162 partially protected vaccinated
      rhesus macaques against pathogenic SHIV(SF162P4) virus. Extending our studies to
      subtype C isolate TV1, we have purified o-gp140DeltaV2TV1 (subtype C DeltaV2
      trimer) to homogeneity, performed glycosylation analysis, and determined its
      ability to bind CD4, as well as a panel of well-characterized neutralizing
      monoclonal antibodies (mAb). In general, critical epitopes are preserved on the
      subtype C DeltaV2 trimer; however, we did not observe significant binding for the
      b12 mAb. The molecular mass of subtype C DeltaV2 trimer was found to be 450 kDa,
      and the hydrodynamic radius was found to be 10.87 nm. Our data suggest that
      subtype C DeltaV2 trimer binds to CD4 with an affinity comparable to o
      gp140DeltaV2SF162 (subtype B DeltaV2 trimer). Using isothermal titration
      calorimetric (ITC) analysis, we demonstrated that all three CD4 binding sites
      (CD4-BS) in both subtype C and B trimers are exposed and accessible. However,
      compared to subtype B trimer, the three CD4-BS in subtype C trimer have different
      affinities for CD4, suggesting a cooperativity of CD4 binding in subtype C trimer
      but not in subtype B trimer. Negative staining electron microscopy of the subtype
      C DeltaV2 trimer has demonstrated that it is in fact a trimer. These results
      highlight the importance of studying subtype C Env, and also of developing
      appropriate subtype C-specific reagents that may be used for better immunological
      characterization of subtype C Env for developing an AIDS vaccine.

PMID- 18061233
TI  - Mixed carbon sources for nitrate reduction in activated sludge-identification of
      bacteria and process activity studies.
AB  - Mixtures of methanol and acetate as carbon source were investigated in order to
      determine their capacity to enhance denitrification and for analysis of the
      microbial composition and carbon degradation activity in activated sludge from
      wastewater treatment plants. Laboratory batch reactors at 20 degrees C were used
      for nitrate uptake rate (NUR) measurements in order to investigate the anoxic
      activity, while single and mixed carbon substrates were added to activated
      sludge. Microautoradiography (MAR) in combination with fluorescence in situ
      hybridisation (FISH) were applied for microbial analysis during exposure to
      different carbon sources. The NUR increased with additions of a mixture of
      acetate and methanol compared with additions of a single carbon source. MAR-FISH
      measurements demonstrated that the probe-defined group of Azoarcus was the main
      group of bacteria utilising acetate and the only active group utilising methanol
      under anoxic conditions. The present study indicated an improved denitrification
      potential by additions of a mixed carbon source compared with commonly used
      single-carbon additions. It is also established that Azoarcus bacteria are
      involved in the degradation of both acetate and methanol in the anoxic activated
      sludge.

PMID- 18061232
TI  - Cell-surface processing of extracellular human immunodeficiency virus type 1 Vpr
      by proprotein convertases.
AB  - Increasing evidence suggests that extracellular Vpr could contribute to HIV
      pathogenesis through its effect on bystander cells. Soluble forms of Vpr have
      been detected in the sera and cerebrospinal fluids of HIV-1-infected patients,
      and in vitro studies have implicated extracellular Vpr as an effector of cellular
      responses, including G2 arrest, apoptosis and induction of cytokines and
      chemokines production, presumably through its ability to transduce into multiple
      cell types. However, the mechanism underlying Vpr release from HIV-1-producing
      cells remains undefined and the biological modifications that the extracellular
      protein may undergo are largely unknown. We provide evidence indicating that
      soluble forms of Vpr are present in the extracellular medium of HIV-1-producing
      cells. Release of Vpr in the extracellular medium did not originate from decaying
      or disrupted HIV-1 virions that package Vpr but rather appeared associated with
      HIV-1-mediated cytopathicity. Interestingly, Vpr was found to undergo proteolytic
      processing at a very well conserved proprotein convertase (PC) cleavage site,
      R(85)QRR(88) downward arrow, located within the functionally important C-terminal
      arginine-rich domain of the protein. Vpr processing occurred extracellularly upon
      close contact to cells and most likely involved a cell surface-associated PC.
      Consistently, PC inhibitors suppressed Vpr processing, while expression of
      extracellular matrix-associated PC5 and PACE4 enhanced Vpr cleavage. PC-mediated
      processing of extracellular Vpr led to the production of a truncated Vpr product
      that was defective for the induction of cell cycle arrest and apoptosis when
      expressed in human cells. Collectively, these results suggest that cell surface
      processing of extracellular Vpr by PCs might regulate the levels of active
      soluble Vpr.

PMID- 18061234
TI  - Effect of silica and pH on arsenic uptake by resin/iron oxide hybrid media.
AB  - The recently imposed maximum contaminant level (MCL) of 10microg/L for arsenic
      has necessitated many water providers to implement efficient treatment systems to
      reduce the arsenic content in potable water supplies across the United States. A
      popular, cost-effective solution is to adsorb the arsenic onto hydrous iron oxide
      based granular media. Hybrid media, consisting of hydrous iron oxides impregnated
      into a polymeric substrate in order to improve mechanical stability, have also
      been developed. The effective operational bed life of these adsorptive media is
      strongly dependent on the chemistry of the water being treated. High levels of
      silica combined with pH values greater than 8 have been shown to have a
      detrimental effect on the arsenic removal efficiency of all adsorptive media.
      Batch arsenate (arsenic(V)) adsorption experiments were performed to evaluate the
      effect of pH and silica on the static arsenic capacity of two iron oxide-based
      hybrid media, ArsenX(np) (a commercially available media) and npRio (a
      developmental media). From the data obtained, it was evident that the presence of
      increased levels of silica enhanced the detrimental effect of elevated pH on
      arsenic capacity, being most noticeable at pH 8 and above. In a solution
      containing 30ppm of SiO(2), a decrease in arsenic capacity as high as 71.8% was
      observed when the pH was increased from 7 to 9. Reducing the pH of the water
      prior to treatment may therefore be an economic option for improving media
      performance in drinking waters containing high concentrations of silica.

PMID- 18061235
TI  - Surface catalyzed Fenton treatment of bis(2-chloroethyl) ether and bis(2
      chloroethoxy) methane.
AB  - This study examined the feasibility of using surface catalyzed Fenton treatment
      to remediate soil and groundwater contaminated by the chlorinated ethers, bis(2
      chloroethyl) ether (BCEE) and bis(2-chloroethoxy) methane (BCEM). Parameters that
      affect the contaminant loss rate such as porewater pH, hydrogen peroxide
      concentration, and solid/water ratio were systematically evaluated. Batch
      reactors were set-up utilizing either contaminated or uncontaminated soil,
      obtained from an industrial site in Moss Point, MS, that was mixed with synthetic
      groundwater containing the contaminants of interest. The results show an increase
      in contaminant reduction with a decrease in pH, an increase in hydrogen peroxide
      concentration, or an increase in the solid/water ratio. For a similar set of
      conditions, contaminant reduction was greater for systems utilizing contaminated
      soil as compared to the systems containing uncontaminated soil. In addition,
      specific oxygen uptake rates (SOURs) were measured for biomass, collected from an
      activated sludge plant, exposed to different dilutions of untreated and surface
      catalyzed Fenton treated water to evaluate whether residual BCEE, BCEM, and their
      co-contaminants as well as their oxidation by-products were potentially
      inhibitory or can potentially serve as a substrate for the biomass. The measured
      SOURs show that the surface catalyzed Fenton treatment enhanced the
      biodegradability of the contaminated groundwater and served as a substrate for
      the biomass.

PMID- 18061236
TI  - Catalytic effects by metal oxides on the formation and degradation of chlorinated
      aromatic compounds in fly ash.
AB  - Polychlorinated benzenes, dibenzo-p-dioxins (PCDD), and dibenzofurans (PCDF) may
      be formed below the combustion temperature in fly ash from municipal solid waste
      incinerators (MSWI). Copper catalyzes this formation, possibly by the Deacon
      reaction. Many other elements are also Deacon catalysts or promoters, and here we
      report results from a statistically designed experiment with 15 metal oxides
      added to fly ash and heated at 300 degrees C for 2h in an air atmosphere. A
      resolution IV fractional factorial design with four replicates was completed in
      36 runs with the oxides of magnesium, yttrium, titanium, vanadium, niobium,
      chromium, molybdenum, tungsten, manganese, iron, cobalt, nickel, copper, zinc,
      and tin. All samples were analyzed for chlorinated benzenes and the results were
      evaluated by analysis of variance. The addition of copper significantly increased
      the amounts of the chlorinated benzenes, while cobalt, chromium and vanadium
      decreased the net formation. The oxides of zinc and iron seemed to have a
      slightly positive and negative effect respectively. The findings in this study
      seem to corroborate our previously reported results regarding the different
      catalytic effects of copper and chromium, and lack of a significant effect by
      nickel. Besides chromium, it also identifies cobalt and vanadium as potent
      catalysts for oxidative degradation of the chlorinated aromatic compounds found
      in MSWI fly ash.

PMID- 18061237
TI  - Long-term effects of mercury in a salt marsh: hysteresis in the distribution of
      vegetation following recovery from contamination.
AB  - During four decades, the Ria de Aveiro was subjected to the loading of mercury
      from a chlor-alkali industry, resulting in the deposition of several tons of
      mercury in the sediments. The present study evaluates the impact of this
      disturbance and the recovery processes, temporally and spatially, by means of
      examining the richness of the species of salt marsh plants and mercury
      concentrations in sediments over the last fifty years. The temporal assessment
      showed that the mercury loading induced a shift in the species composition of the
      salt marsh from a non-disturbed salt marsh with higher species richness to an
      alternative state dominated by Phragmites australis. The horizontal assessment,
      through a mercury gradient, presents the same trend, indicating that P. australis
      is the species most tolerant to higher mercury concentrations, comparative to
      Halimione portulacoides, Arthrocnemum fruticosum, Triglochin maritima, Juncus
      maritimus and Scirpus maritimus. After the reduction of mercury discharges in
      1994, the salt marsh shows a slowly return path recovery response. The hysteresis
      in the response results in the temporal gap between the reduction in mercury
      concentrations in the sediment and the salt marsh species richness response,
      comparatively to the existing diversity in the local reference marsh.

PMID- 18061238
TI  - Removal and degradation of aromatic compounds from a highly polluted site by
      coupling soil washing with photocatalysis.
AB  - The possible application of two environmental remediation technologies - soil
      washing and photocatalysis - to remove and decompose various aromatic pollutants
      present in excavated soils of a contaminated industrial site has been
      investigated. Aqueous solutions containing the non-ionic surfactant Brij 35 were
      used to extract the contaminants from the soil samples. The photocatalytic
      treatment of the obtained washing wastes, performed in the presence of TiO(2)
      suspensions irradiated with simulated sunlight, showed a slow abatement of the
      toxic compounds due to the relevant concentrations of organics in the waste. A
      neat improvement of the process performances, obtained by operating in the
      presence of added potassium peroxydisulfate, suggests a feasible treatment route.

PMID- 18061239
TI  - Potential application of highly reactive Fe(0)/Fe3O4 composites for the reduction
      of Cr(VI) environmental contaminants.
AB  - We describe the use of highly reactive Fe(0)/Fe3O4 composites for the reduction
      of Cr(VI) species in aqueous medium. The composites were prepared by simple
      mechanical alloying of metallic iron and magnetite in different proportions, i.e.
      Fe(0) 25, 50, 75 and 90wt%. While after 3h of reaction pure Fe(0) and pure Fe3O4
      showed only a low reduction efficiency of 15% and 25% Cr(VI) conversion,
      respectively, the composites, in particular Fe(0)(25wt%)/Fe3O4, showed a
      remarkable activity with ca. 65% Cr(VI) conversion. Kinetic experiments showed a
      high reaction rate during the first 3h, which subsequently decreased strongly,
      probably due to a pH increase from 6 to 8. Experiments with composites based on
      Fe(0)/alpha-Fe2O3, Fe(0)/gamma-Fe2O3 and Fe(0)/FeOOH showed very low activities,
      suggesting that Fe(oct)2+ in the magnetite structure plays an important role in
      the reaction. Scanning and high resolution electron microscopies and Mossbauer
      spectra (transmission and conversion electron Mossbauer spectroscopy) indicated
      that the mechanical alloying process promotes a strong interaction and interface
      between the metallic and oxide phases, with the Fe(0) particles completely
      covered by Fe3O4 particles. The high efficiency of the composite Fe(0)/Fe3O4 for
      Cr(VI) reduction is discussed in terms of a special mechanism where an electron
      is transferred from Fe(0) to magnetite to reduce Fe(oct)3+ to Fe(oct)2+, which is
      active for Cr(VI) reduction.

PMID- 18061240
TI  - Production and characterization of sintered ceramics from paper mill sludge and
      glass cullet.
AB  - Three different types of paper mill sludge were first incinerated and then
      attrition milled separately or mixed with glass cullet in varying proportions to
      obtain powders of different compositions. These powders were then dried, sieved,
      uniaxially pressed into samples and air sintered. Fired samples were
      characterized by density, water absorption, shrinkage on firing, strength,
      hardness and fracture toughness measurements; SEM and X-ray diffractions were
      also carried out to investigate microstructure and phase composition. Some
      sintered samples displayed fairly good physical and mechanical properties as a
      consequence of their low residual porosity and fine microstructure.

PMID- 18061241
TI  - CV-0, an early Pleistocene human phalanx from Cueva Victoria (Cartagena, Spain).

PMID- 18061242
TI  - Modeling the impact of sea-spray on particle concentrations in a coastal city.
AB  - With the worlds population becoming increasingly focused on coastal locations
      there is a need to better understand the interactions between anthropogenic
      emissions and marine atmospheres. Herein an atmospheric chemistry-transport model
      is used to assess the impacts of sea-spray chemistry on the particle composition
      in and downwind of a coastal city--Vancouver, British Columbia. It is shown that
      the model can reasonably represent the average features of the gas phase and
      particle climate relative to in situ measurements. It is further demonstrated
      that reactions in/on sea-spray affect the entire particle ensemble and
      particularly the size distribution of particle nitrate, but that the importance
      of these heterogeneous reactions is critically dependent on both the initial
      vertical profile of sea spray and the sea-spray source functions. The results
      emphasize the need for improved understanding of sea spray production and
      dispersion and further that model analyses of air quality in coastal cities
      conducted without inclusion of sea-spray interactions may yield mis-leading
      results in terms of emission sensitivities of particle composition and
      concentrations.

PMID- 18061243
TI  - Effect of biodegradable amendments on uranium solubility in contaminated soils.
AB  - Chelate-assisted phytoextraction has been proposed as a potential tool for
      phytoremediation of U contaminated sites. In this context, the effects of five
      biodegradable amendments on U release in contaminated soils were evaluated. Three
      soils were involved in this study, one with a relatively high background level of
      U, and two which were contaminated with U from industrial effluents. Soils were
      treated with 5 mmol kg(-1) dry weight of either citric acid, NH(4)-citrate/citric
      acid, oxalic acid, S,S-ethylenediamine disuccinic acid or nitrilotriacetic acid.
      Soil solution concentration of U was monitored during 2 weeks. All amendments
      increased U concentration in soil solution, but citric acid and NH(4)
      citrate/citric acid mixture were most effective, with up to 479-fold increase.
      For oxalic acid, S,S-ethylenediamine disuccinic acid and nitrilotriacetic acid,
      the increase ranged from 10-to 100-fold. The highest concentrations were observed
      1 to 7 days after treatment, after which U levels in soil solution gradually
      decreased. All amendments induced a temporary increase of soil solution pH and
      TOC that could not be correlated with the release of U in the soil solution.
      Thermodynamic stability constants (log K) of complexes did not predict the
      relative efficiency of the selected biodegradable amendments on U release in soil
      solution. Amendments efficiency was better predicted by the relative affinity of
      the chelate for Fe compared to U.

PMID- 18061244
TI  - Accumulation and effects of metals in caged carp and resident roach along a metal
      pollution gradient.
AB  - Metal accumulation and effects on plasma Ca(2+), alanine transaminase (ALT) and
      fish condition factor were examined in caged carp (Cyprinus carpio) and resident
      roach (Rutilus rutilus) at four locations along the Grote Nete River system
      (Belgium). Cadmium and zinc accumulation were found in carp and roach, with
      highest concentrations at the most contaminated site (dissolved Cd: 1.82
      microg/l, Zn: 967 microg/l). On the tissue level, highest cadmium concentrations
      were measured in kidneys of carp and roach, followed by gills, intestine and
      liver, while low concentrations were observed in carcass and muscle. For zinc, a
      similar pattern was observed (intestine>kidney>gills>liver>carcass>muscle).
      Comparison between species showed higher cadmium concentrations in feral roach,
      while zinc levels were lower, owing to the high zinc concentrations in control
      carp. Furthermore, comparison of metal concentrations between two sampling
      periods (2005 and 2000-2001) revealed a drastic decrease in cadmium concentration
      in gills, liver and muscle of roach, similar to the reduction in waterborne
      cadmium concentrations, while differences for zinc were much less pronounced. In
      addition to metal accumulation, increased metallothionein concentrations
      (approximately 2x) were found in carp and roach, while no metal-related effects
      were found on ALT, Ca(2+)or condition factor. However, negative effects on fish
      community structure, as assessed by the index of biotic integrity (IBI), were
      found along the pollution gradient and indicated long-term adverse effects of
      metal pollution.

PMID- 18061245
TI  - Atmosphere pollutants and mortality rate of respiratory diseases in Beijing.
AB  - In this paper, we apply the method of Granger causality, which is more accurate
      than classical correlation analysis method, to determine whether the main air
      pollutants--Nitrogen oxides (NO(x)), SO(2) (Sulfur Dioxide), CO (carbon
      monoxide), TSP (total suspended particulates), PM(10) (particulate matter smaller
      than 10 microns)--and the mortality of respiratory diseases of the residents in
      Beijing have causal relationship. After ensuring NO(x), SO(2) and CO as the
      responsible substances, we use the time series method to construct the
      autoregressive integrated moving average model (ARIMA) of the pollutants, so that
      we could predict the amount of the pollutants from 2005 to 2008. Then we use the
      predicted value of pollutants as the input of the neural network model and obtain
      the output as the change of the death rate of respiratory diseases from 2005 to
      2008. In the end, reducing the amount of pollutants by 10% and inputting the data
      in the neural network model, we make the prediction to evaluate the level of the
      pollutants and concluded that NO(x) is the most important pollutant to control.

PMID- 18061246
TI  - Growth and physiological responses of beech seedlings to long-term exposure of
      acid fog.
AB  - Seven-year-old beech seedlings (Fagus crenata) were exposed to simulated acid fog
      (SAF) at pH 3 or pH 5 (as control) prepared by adding a 2:1:1 mixture (molar
      ratio) of nitric acid, ammonium sulfate, and sodium chloride to ultrapure water
      from September 2004 to July 2006 in a mobile fog chamber. In comparison to
      control seedlings, seedlings from the pH 3 treatment displayed inferior plant
      height, stem diameter, number of leaves, and dry matter production, but greater
      leaf area. Furthermore, exposure to SAF induced early falling of leaves with a
      nearly two-times-greater normalized leaf number index than control. The starch
      levels in the stems of seedlings of the pH 3 treatment were much lower than those
      of control at the harvest. The acid fog-induced reduction of the starch
      accumulation is considered to occur mainly because of fewer leaves during the
      growth phase. Results of laboratory experiments demonstrate that the amount of
      base cations leached from the beech leaves increased with decreasing pH of SAF;
      the leaching amount of calcium ion from the beech was high relative to that of
      conifers such as fir and cedar. These results imply that chronic acid fog
      exposure suppresses growth and physiological activity of beech seedlings.

PMID- 18061247
TI  - Thrombopoietin and reticulated platelets as thrombopoietic markers in colorectal
      cancer.

PMID- 18061248
TI  - The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma
      in patients with a pelvic mass.
AB  - OBJECTIVES: The CA125 tumor marker is used to help predict the presence of
      ovarian cancer in patients with an adnexal mass. Because elevated CA125 levels
      occur in many benign gynecologic conditions, we set out to identify other novel
      biomarkers that would increase the sensitivity and specificity of CA125. METHODS:
      Serum and urine samples were obtained preoperatively from women undergoing
      surgery for an adnexal mass. The samples were analyzed for levels of CA125, SMRP,
      HE4, CA72-4, activin, inhibin, osteopontin, epidermal growth factor (EGFR), and
      ERBB2 (Her2) and were compared to final pathology results. Logistic regression
      models were estimated for all markers and combinations, with cross-validation
      analysis performed to obtain the sensitivities at set specificities of 90%, 95%,
      and 98%. RESULTS: Two hundred and fifty-nine patients with adnexal masses were
      enrolled. Of these, 233 patients were eligible for analysis with 67 invasive
      epithelial ovarian cancers and 166 benign ovarian neoplasms. Mean values for all
      marker levels except Her2 differed significantly between patients with benign
      masses and cancer. As a single marker, HE4 had the highest sensitivity at 72.9%
      (specificity 95%). Comparatively, combined CA125 and HE4 yielded the highest
      sensitivity at 76.4% (specificity 95%), with additional markers adding minimally
      to the sensitivity of this combination. HE4 was the best single marker for Stage
      I disease, with no increase in sensitivity when combined with CA125 or any other
      marker. CONCLUSIONS: As a single tumor marker, HE4 had the highest sensitivity
      for detecting ovarian cancer, especially Stage I disease. Combined CA125 and HE4
      is a more accurate predictor of malignancy than either alone.

PMID- 18061249
TI  - Treatment options in stage I endometrial stromal sarcoma: a retrospective
      analysis of 53 cases.
AB  - OBJECTIVE: To discuss the optimal treatment options for stage I patients with
      endometrial stromal sarcoma (ESS). METHODS: We reviewed hospital records and
      pathology of 53 patients with ESS at stage I. Statistical analysis was performed
      using SPSS 12.0 software, and Chi-square test, t-test and log rank test were
      adopted. RESULTS: Among 53 patients, 37 had low-grade tumors, 11 had
      undifferentiated endometrial sarcoma (UES) and 5 had unclassified ESS. The median
      follow-up time was 66 months, and 48 cases were still alive. The overall 2-year
      and 5-year survival rates were 91.5% and 85.9%, respectively. The recurrence rate
      of the patients with preserved ovarian function was remarkably higher than that
      of patients without (100% vs. 22.7%, P<0.001). The patients who received adjuvant
      whole pelvic radiation (Dt 40 approximately 45 Gy) had obviously higher local
      control rate than the patients who did not (93.8% vs. 57.1%, P=0.007), but they
      had similar survival (P=0.963). Among 7 of the 11 UES patients without distant
      recurrence, 5 received the adjuvant chemotherapy with IAP (ifosfamide 1.0 g, d1
      4; epirubicin 25 mg/m2, d1-2; cisplatin 20 mg, d1-5; mensa 0.2 g, 0, 4, 8 h from
      the application of ifosfamide, d1-4, q 28 days) or VAD (vincristine 1.2 mg/m2,
      d1; adriamycin 20 mg/m2, d1-3; dacarbazine 250 mg/m2, d1-5, q 28 days), and none
      of the other 4 cases recurring distantly received the chemotherapy with IAP or
      VAD. CONCLUSIONS: Surgeries not preserving ovarian function were helpful to
      decrease the risk of recurrence compared with those surgeries sparing ovarian
      function. Adjuvant radiotherapy could improve local control but not survival.
      Adjuvant chemotherapy with IAP or VAD seemed to be beneficial to UES patients.

PMID- 18061250
TI  - Improved anti-tumor therapy based upon infectivity-enhanced adenoviral delivery
      of RNA interference in ovarian carcinoma cell lines.
AB  - BACKGROUND: Hec1 (Highly Expressed in Cancer gene 1) has recently been shown to
      play an important role in the proper segregation of chromosomes during mitosis.
      Recently, an adenovirus delivery system carrying RNA interference (RNAi) of Hec1
      has been reported in a cervical adenocarcinoma model. Adenoviral delivery
      systems, however, have the main limitation of poor viral infectivity due to lack
      of the native receptor, Coxsackie-Adenovirus Receptor (CAR), on the surface of
      tumor cells. We hypothesize that the viral infectivity of the adenovirus vector
      would be enhanced via a CAR-independent pathway by altering the targeting
      tropism, thus increasing the knockdown effect of Hec1 expression in ovarian
      carcinoma cells. METHODS: Two adenoviruses (Ad-siRNA-Hec1 and Ad-siRNA
      Hec1.F5/3), along with a negative control (Ad-siRNA-GAPDH.F5/3), were created
      using homologous recombination. HEY and SKOV3.ip1 cell lines were used to perform
      experiments. The following assays were then used to determine RNAi knockdown
      efficiency: (1) quantitative PCR (QPCR), (2) Western blot, (3) MTS assay, (4)
      Annexin V-FITC FACS, (5) crystal violet staining. In all experiments, a negative
      control served as a baseline measure. RESULTS: QPCR demonstrated a 2-log viral
      infectivity enhancement with Ad-siRNA-Hec1.F5/3 over Ad-siRNA-Hec1. QPCR at 72 h
      revealed mRNA knockdown induced by Ad-siRNA-Hec1 and Ad-siRNA-Hec1.F5/3 in
      SKOV3.ip1 and HEY cells, respectively (71%/60%, and 32%/78% mRNA knockdown
      compared to negative control). Western blot revealed translational inhibition
      induced by both Hec1 Ads with the least knockdown seen with Ad-siRNA-GAPDH.F5/3.
      FACS analysis revealed increased annexin V positivity in RNAi-infected cells,
      suggesting a higher rate of apoptosis. MTS assay indicated increased cell death 8
      days post-infection with Ad-siRNA-Hec1 and Ad-siRNA-Hec1.F5/3 in SKOV3.ip1 and
      HEY cell lines, respectively (75% vs. 35% and 43% vs. 12% viable cells). Crystal
      violet staining revealed increased cell death with Ad-siRNA-Hec1.F5/3 in all
      tested cell lines. CONCLUSIONS: RNAi against Hec1 results in gene expression
      knockdown and apoptosis in vitro. The infectivity-enhanced adenovirus as delivery
      mechanism shows potential application in future gene therapy models of RNAi in
      ovarian cancer.

PMID- 18061251
TI  - Postcalving factors affecting conception risk in Holstein dairy cows in tropical
      and sub-tropical conditions.
AB  - The objective was to identify postpartum risk factors between nutritional
      imbalance and health disorders affecting first-service conception risk (FSCR) in
      21 commercial Holstein herds in Reunion Island. Multivariate logistic-regression
      models including herd as a random effect were used to analyze the relationship
      between FSCR and energy status, nitrogen status, hepatic function, mineral
      deficiencies, and postpartum health disorders. Two models (A and B) were built on
      two subsets of data (n=446 and n=863) with risk indicators measured during the
      first month of lactation and around time of first service, respectively, adjusted
      for season, breed, parity, origin, milk yield, calving to first service interval
      (CS1), and type of estrus (spontaneous vs. induced). The averaged conception risk
      was 0.266+/-0.015 (n=913) (mean+/-S.E.M.). In both models, FSCR was decreased by
      CS1 < or = 60 d and induced estrus. In model A, FSCR was decreased (p<0.05) for
      cows with mean cumulative 100 d daily milk yield < or =23 kg/d and >27 kg/d, with
      losses of body condition score >1.5, and with retained placenta. In model B, FSCR
      was decreased (p<0.05) for cows inseminated during wet season, previously raised
      out of the farm as nulliparous, with blood magnesium concentration < or =0.9
      mmol/L, and for high-yielding cows (100 d milk yield > 27 kg/d) with glutamate
      deshydrogenase>17 UI/L. Hence, high-body-lipid mobilization during the first
      month of lactation was a strong nutritional predictor of low FSCR together with
      liver damage in high-yielding cows. Interestingly, our models revealed that
      infertility is better related to nutritional factors than to postpartum health
      disorders occurrence.

PMID- 18061252
TI  - Hepatocellular carcinoma: epidemiology and clinical aspects.
AB  - Liver cancer is one of the most frequent solid cancers that kills more than
      650,000 people around the world each year. Though great improvements have been
      done in last 10 years on the understanding the molecular mechanisms involved in
      liver oncogenesis, the prognosis of patients affected by liver cancer is still
      poor for most of them. Even in those where a relatively early diagnosis is done,
      the course of the disease is often fatal due to the underlying liver cirrhosis.
      In this review authors report the most recent findings on the pathogenesis of
      liver cancer and on therapeutic approaches, included those emerging from the most
      recent literature.

PMID- 18061253
TI  - Foods and liver health.
AB  - Chronic liver damage is a worldwide common pathology, characterised by an
      inflammatory and fibrotic process that leads to a progressive evolution from
      chronic hepatitis to cirrhosis and hepatocellular carcinoma (HCC). A major role
      for fats and oxidative stress has been recently demonstrated in the pathogenesis
      of liver diseases. In the clinical practice, dietary recommendations in the
      management of chronic diseases often rely on denying patients certain foods,
      which results in a severe reduction of quality of life. In this paper a new
      perspective based on the development of Food intended for Specific Medical
      Purposes (FSMP) containing highly bioavailable antioxidant compounds or
      polyunsaturated-fatty acids, has been highlighted as a tool for preventive and
      curative medicine, to be associated to pharmacological treatments.

PMID- 18061254
TI  - Isoprostanes and hepatic fibrosis.
AB  - After a brief introduction to oxidative stress, the discovery of F(2)
      isoprostanes as specific and reliable markers of oxidative stress is described.
      Isoprostanes are also agonists of important biological effects. Since a relation
      between oxidative stress and collagen hyperproduction has been previously
      suggested and since lipid peroxidation products have been proposed as possible
      mediators of liver fibrosis, we investigated whether collagen synthesis is
      induced by F(2)-isoprostanes the most proximal products of lipid peroxidation. In
      a rat model of carbon tetrachloride-induced hepatic fibrosis, plasma isoprostanes
      were markedly elevated for the entire experimental period; hepatic collagen
      content was also increased. When hepatic stellate cells from normal liver were
      cultured up to activation (expression of alpha-smooth muscle-alpha actin) and
      then treated with F(2)-isoprostanes in the concentration range found in the in
      vivo studies (10(-9)-10(-8)M), a striking increase in DNA synthesis, in cell
      proliferation and in collagen synthesis was observed. Moreover, F(2)-isoprostanes
      increased the production of transforming growth factor-beta1 by U937 cells,
      assumed as a model of Kupffer cells or liver macrophages. The data suggest the
      possibility that F(2)-isoprostanes generated by lipid peroxidation in hepatocytes
      mediate hepatic stellate cell proliferation and collagen hyperproduction seen in
      hepatic fibrosis.

PMID- 18061255
TI  - The effect of different storage conditions and duration on the fracture strength
      of three types of translucent fiber posts.
AB  - OBJECTIVES: (a) To evaluate the effects of storage duration, storage condition
      and type of fiber post on post fracture strength. (b) To morphologically evaluate
      the post structure before and after storage. METHODS: Three types of fiber posts
      were divided in different groups (n=14) according to the storage duration (1, 6,
      12 months), and storage condition (dry at 37 degrees C; saline water at 37
      degrees C; mineral oil at 37 degrees C and storage inside the roots of extracted
      human teeth immersed in saline water at 37 degrees C). Specimens were loaded in a
      universal testing machine with a compressive load until fracture. A 3-way ANOVA
      and Tukey's test (alpha=.05) were used to compare the effect of the experimental
      factors on the fracture strength. Two posts of each group were observed before
      and after the storage using a scanning electron microscope. RESULTS: Storage
      conditions and post type, had a significant effect on post fracture strength
      (p<0.05). The interaction between these factors was significant (p<0.05). Water
      storage significantly decreased the fracture strength, regardless of the post
      type and the storage duration. Storage inside roots, in oil, and at dry
      conditions did not significantly affect post fracture strength. SEM micrographs
      revealed voids between fibers and resin matrix for posts stored in water. Posts
      stored under the other conditions showed a compact matrix without porosities.
      SIGNIFICANCE: Fiber posts placed inside human root canals immersed in water are
      not affected by the detrimental effect of water.

PMID- 18061256
TI  - Prevention of Staphylococcus epidermidis biofilm formation using a low
      temperature processed silver-doped phenyltriethoxysilane sol-gel coating.
AB  - Sol-gel coatings which elute bioactive silver ions are presented as a potential
      solution to the problem of biofilm formation on indwelling surfaces. There is
      evidence that high-temperature processing of such materials can lead to diffusion
      of silver away from the coating surface, reducing the amount of available silver.
      In this study, we report the biofilm inhibition of a Staphylococcus epidermidis
      biofilm using a low-temperature processed silver-doped phenyltriethoxysilane sol
      gel coating. The incorporation of a silver salt into a sol-gel matrix resulted in
      an initial high release of silver in de-ionised water and physiological buffered
      saline (PBS), followed by a lower sustained release for at least 6 days-as
      determined by graphite furnace-atomic absorption spectroscopy (GF-AAS). The
      release of silver ions from the sol-gel coating reduced the adhesion and
      prevented formation of a S. epidermidis biofilm over a 10-day period. The
      presence of surface silver before and after 24 h immersion in PBS was confirmed
      by X-ray photoelectron spectroscopy (XPS). These silver-doped coatings also
      exhibited significant antibacterial activity against planktonic S. epidermidis. A
      simple test to visualise the antibacterial effect of silver release coatings on
      neighbouring bacterial cultures is also reported.

PMID- 18061257
TI  - Upconversion fluorescence imaging of cells and small animals using lanthanide
      doped nanocrystals.
AB  - Upconversion fluorescence imaging technique with excitation in the near-infrared
      (NIR) region has been used for imaging of biological cells and tissues. This has
      several advantages, including absence of photo-damage to living organisms, very
      low auto-fluorescence, high detection sensitivity, and high light penetration
      depth in biological tissues. In this report we demonstrate the use of a new
      upconversion fluorophore, lanthanide doped nanocrystals, for imaging of cells and
      some deep tissues in animal. Polyethyleneimine (PEI) coated NaYF(4):Yb,Er
      nanoparticles were synthesized, which produce very strong upconversion
      fluorescence when excited at 980 nm by a NIR laser. The nanoparticles were shown
      to be stable in physiologic buffered saline (PBS), non-toxic to bone marrow stem
      cells, and resistant to photo-bleaching. The nanoparticles delivered into some
      cell lines or injected intradermally and intramuscularly into some tissues either
      near the body surface or deep in the body of rats showed visible fluorescence,
      when exposed to a 980 nm NIR laser. To the best of our knowledge, this represents
      the first demonstration of use of upconversion fluorophores for cellular and
      tissue imaging.

PMID- 18061258
TI  - Placental 11beta-hydroxysteroid dehydrogenase type 2 is reduced in pregnancies
      complicated with idiopathic intrauterine growth Restriction: evidence that this
      is associated with an attenuated ratio of cortisone to cortisol in the umbilical
      artery.
AB  - The placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) serves as
      a functional barrier to protect the fetus from excessive exposure to high levels
      of maternal cortisol. There is evidence that placental 11beta-HSD2 is reduced in
      pregnancies complicated with intrauterine growth restriction (IUGR), but the
      relationship between the two is uncertain owing to other maternal complications
      often associated with this pathological condition of pregnancy. To gain insight
      into the role of placental 11beta-HSD2 in the pathogenesis of IUGR, we studied
      variations in the activity and expression of this important enzyme as well as its
      functional indicator, the ratio of cortisone to cortisol in umbilical cord blood,
      in a cohort of 12 term deliveries complicated with idiopathic IUGR and 12 term
      controls. We showed that both placental 11beta-HSD2 activity and mRNA were
      reduced in IUGR. This was accompanied by a decrease in the ratio of cortisone to
      cortisol in the umbilical artery, suggesting that not only placental but also
      fetal 11beta-HSD2 activity may be compromised in idiopathic IUGR. Given that we
      previously identified the nuclear receptor PPARdelta as a potent suppressor of
      placental 11beta-HSD2, we also tested but found no evidence to support the
      hypothesis that placental PPARdelta expression is increased in IUGR thereby
      contributing to the molecular mechanisms that underlie the attenuated placental
      11beta-HSD2. Taken together, our present findings provide evidence suggesting a
      role for an attenuated placental as well as fetal 11beta-HSD2 in the pathogenesis
      of IUGR.

PMID- 18061259
TI  - Chlamydia psittaci in MALT lymphomas of ocular adnexals: the Austrian experience.
AB  - The presence of Chlamydia (C.) psittaci, C. pneumoniae and C. trachomatis DNAs in
      MALT lymphomas of ocular adnexals from 13 Austrian patients were studied.
      Gastrointestinal MALT lymphomas and gastritis specimens served as controls. Of 13
      MALT lymphomas of the ocular adnexals, seven were positive for C. psittaci DNA.
      In contrast, one of 17 gastrointestinal specimens tested positive. All specimens
      were negative for C. trachomatis and C. pneumoniae DNAs. In conclusion, C.
      psittaci infection was observed in the majority of MALT lymphomas of ocular
      adnexals in Austrian patients.

PMID- 18061260
TI  - Is there a link between hypospadias and organochlorine exposure in East Greenland
      sledge dogs (Canis familiaris)?
AB  - In a clinical survey on East Greenland male sledge dogs (Canis familiaris), one
      dog exhibited malformation of the external genital organs. The clinically in situ
      examination of the sledge dog revealed a rare congenital malformation of the
      urethra and penis corresponding to severe perineal and penile hypospadias. The
      testes showed spermiogenesis and no sign of true hermaphroditism. We did not have
      the opportunity to examine the dam for endocrine organ pathology or tumours. But,
      based on organochlorine data in ringed seal (Phoca hispida) blubber and
      information from the owners, the potential in uteri OC exposure of the sledge dog
      was estimated to 320 microg/day which correspond to 128 pg TEQ/kg/day. This is 32
      128-folds above WHO guidelines and threshold levels for teratogen and
      reproductive effects. We suggest that the congenital malformation was due to
      endocrine organ pathology/tumours of the dam, enzyme/receptor defects (mutation)
      in the pup or in uteri exposure to environmental xenoestrogens.

PMID- 18061262
TI  - The possible role of retinal dopaminergic system in visual performance.
AB  - It is a well-known fact that the retina is one of the tissues in the body, which
      is richest in dopamine (DA), yet the role of this system in various visual
      functions remains unclear. We have identified 13 types of DA retinal pathologies,
      and 15 visual functions. The pathologies were arranged in this review on a net
      grid, where one axis was "age" (i.e., from infancy to old age) and the other axis
      the level of retinal DA (i.e., from DA deficiency to DA excess, from Parkinson
      disorder to Schizophrenia). The available data on visual dysfunction(s) is
      critically presented for each of the DA pathologies. Special effort was made to
      evaluate whether the site of DA malfunction in the different DA pathologies and
      visual function is at retinal level or in higher brain centers. The mapping of DA
      and visual pathologies demonstrate the pivot role of retinal DA in mediating
      visual functions and also indicate the "missing links" in our understanding of
      the mechanisms underlying these relationships.

PMID- 18061261
TI  - Basal ganglia and dopamine contributions to probabilistic category learning.
AB  - Studies of the medial temporal lobe and basal ganglia memory systems have
      recently been extended towards understanding the neural systems contributing to
      category learning. The basal ganglia, in particular, have been linked to
      probabilistic category learning in humans. A separate parallel literature in
      systems neuroscience has emerged, indicating a role for the basal ganglia and
      related dopamine inputs in reward prediction and feedback processing. Here, we
      review behavioral, neuropsychological, functional neuroimaging, and computational
      studies of basal ganglia and dopamine contributions to learning in humans.
      Collectively, these studies implicate the basal ganglia in incremental, feedback
      based learning that involves integrating information across multiple experiences.
      The medial temporal lobes, by contrast, contribute to rapid encoding of relations
      between stimuli and support flexible generalization of learning to novel contexts
      and stimuli. By breaking down our understanding of the cognitive and neural
      mechanisms contributing to different aspects of learning, recent studies are
      providing insight into how, and when, these different processes support learning,
      how they may interact with each other, and the consequence of different forms of
      learning for the representation of knowledge.

PMID- 18061264
TI  - The protection of wildlife from mortality: hypothesis and results for risk
      assessment.
AB  - Wildlife deaths associated with cyanide-bearing tailings dams are a significant
      environmental issue that has affected the gold mining industries for many years
      and still characterized by little knowledge about how to measure, monitoring,
      reduce or eliminate those deaths. The purpose of this paper is statistically to
      determine: the potential for establishing causal relations between exposure to
      cyanide (in its most common species relevant to tailings) and response (measured
      by death counts), to develop a protocol of data analysis, the understanding of
      the significance of data gaps, and the effect of likely risk management
      interventions to achieve the goals of the International Cyanide Management Code
      (ICMC); [ICMC The International Cyanide Management Institute. International
      cyanide management code, the international cyanide management institute 2005,
      www.cyanidecode.org.]. However, operator's certification under the ICMC is
      difficult because of the limited data and potentially serious under-estimation of
      the death counts. This is due to observational skill and monitoring frequency,
      the small size of the carcasses, large extent of tailings facilities, carcasses
      loss by; entombment in tailings, sink, or taken by scavenging wildlife. This (1st
      order or bounding) assessment results focus on bird-deaths, which appear to be
      most frequent at sites where elevated cyanide concentrations are found. Those
      results indicate that the empirical causal associations we generate support the
      hypotheses that: This paper also develops the basis for a complete risk
      assessment study to be based on additional data gathering activities and detailed
      statistical analyses. These two activities, combined with a risk management plan
      also being developed, will provide a tool for compliance with the ICMC.

PMID- 18061266
TI  - Monovision in LASIK.
AB  - PURPOSE: To evaluate the preoperative characteristics and postoperative outcomes
      of presbyopic and prepresbyopic patients selecting monovision correction by
      LASIK. DESIGN: Retrospective observational case series. PARTICIPANTS: One hundred
      seventy-two sequentially treated myopic and hyperopic patients, 45 years or
      older, who sought LASIK vision correction with the goal of monovision. METHODS:
      Patients treated with monovision correction by LASIK were measured and
      categorized. All treatments were conducted using conventional (nonwavefront)
      technology. MAIN OUTCOME MEASURES: Acuity, refractive and functional success of
      monovision correction based on postoperative manifest refraction relative to
      target correction, and patient enhancement rate. RESULTS: Of 284 consecutively
      treated LASIK patients 45 years or older, 188 (67%) chose to be corrected for
      monovision and 96 (34%) chose bilateral distance correction. Of the patients
      seeking laser vision correction, women (60%) outnumbered men (40%), and women
      selected monovision slightly more often than men (66.9% vs. 60.5%, P = 0.14). A
      majority of patients (85%) chose their dominant eye to be corrected for distance.
      Patients who selected their dominant eye for near vision correction had similar
      acceptance and refractive success rates. Hyperopic patients achieved results
      comparable to those of myopic patients. Of the 172 patients treated with
      monovision correction, only 7% chose to forego monovision and subsequently
      enhance the near eye to distance vision. However, 27.9% of monovision patients
      underwent subsequent enhancement of their distance vision eye. CONCLUSIONS: LASIK
      monovision correction represents a viable and increasingly popular method of
      correcting presbyopic and prepresbyopic patients considering refractive surgery.
      Crossed monovision may be applied successfully to appropriately chosen patients.
      The distance vision eye in the monovision patient may have a lower tolerance for
      residual refractive error and require a higher rate of enhancements than a
      standard laser vision correction patient.

PMID- 18061265
TI  - Impaired dendritic cell differentiation and maturation in the absence of C3.
AB  - Human monocytes can be differentiated into immature dendritic cells (DCs) in the
      presence of serum and cytokines. One of the main functions of immature DCs is to
      capture and process antigens. Following maturation, they differentiate into
      antigen presenting cells. The role of complement in the differentiation process
      from monocytes towards immature DCs remains elusive. Here we demonstrate that
      complement 3 (C3) has a regulatory impact on the expression of specific DC
      surface molecules and DC-derived cytokine production during DC differentiation.
      We isolated human adherent peripheral blood mononuclear cells, which were
      cultured in the presence of GM-CSF plus IL-4 in medium supplemented with normal
      human serum or C3 deficient serum. The lack of C3 during DC differentiation
      negatively impacted the expression of C-type lectin receptor DC-SIGN, the antigen
      presenting molecules HLA-DR and CD1a, and the costimulatory molecules CD80 and
      CD86. Further, the spontaneous production of IL-6 and IL-12 was reduced in the
      absence of C3. Moreover, the maturation of immature DCs in response to LPS
      challenge was impaired in the absence of C3 as evidenced by reduced MHC-II, co
      stimulatory molecule expression as well as modulated IL-12 and TNF-alpha
      production. Collectively, our results provide evidence for a novel role of C3 as
      a critical cofactor in human DC differentiation and maturation.

PMID- 18061267
TI  - Penetrating keratoplasty in Asian eyes: the Singapore Corneal Transplant Study.
AB  - PURPOSE: The Singapore Corneal Transplant Study (SCTS) is a 16-year prospective
      study of 2100 consecutive corneal transplants performed between January 1991 and
      November 2006 in patients from Southeast Asia at a single tertiary center. The
      indications, complications, long-term survival rates, and risk factors for graft
      failure of penetrating keratoplasty (PK) performed in Asian eyes are reported.
      DESIGN: Prospective cohort study. PARTICIPANTS: Of the 2100 corneal transplants,
      1130 consecutive PKs were performed from January 1991 to December 2003. One graft
      per patient was selected, leaving 901 grafts for analysis. METHODS: Data were
      obtained from the Singapore Eye Bank's SCTS database. Cases were classified into
      optical, therapeutic, and tectonic indications and 9 corneal disease groups.
      Twenty-four demographic, preoperative, intraoperative, and donor risk factors
      were subjected to Kaplan-Meier survival analysis, univariate analysis, and
      multivariate analysis by Cox proportional hazards regression modeling. MAIN
      OUTCOME MEASURE: Graft failure, defined as the irreversible loss of optical
      clarity. RESULTS: Study patients were Asian, comprising Chinese (72.7%), Indian
      (11.54%), and Malay (11.1%) ethnicities (mean age, 56.65 years). The mean follow
      up period was 36.8+/-35.5 months. Indications for surgery were optical (87.0%),
      therapeutic (8.1%), and tectonic (4.88%). Main diagnoses were
      pseudophakic/aphakic bullous keratopathy (23.4%), postinfectious scarring
      (12.9%), regrafts (12.4%), keratoconus (9.7%), and posttraumatic scarring (7.3%).
      Kaplan-Meier survival rates for optical grafts were 86.6%, 72.0%, 63.7%, and
      52.0% at 1, 3, 5, and 10 years, respectively; survival rates for therapeutic
      grafts were 78.4%, 58.3%, and 37.3% at 1, 3, and 5 years, and those for tectonic
      grafts were 68.3% and 41.7% at 1 and 3 years. Endothelial rejection and late
      endothelial decompensation accounted for 50.51% of failures. Multivariate
      analysis revealed 9 predictors for graft failure: recipient gender, age, graft
      size, graft endothelial status, primary corneal disease, glaucoma, inflammation,
      perforation, and corneal vascularization. CONCLUSIONS: The long-term outcome for
      optical indications in Asian eyes follows a trend in endothelium-related
      attrition similar to that seen in the West. Tectonic and therapeutic keratoplasty
      for corneal infections and perforation, however, constitute a significant
      proportion of corneal transplantation performed in Asia and carry a graver
      prognosis in terms of graft survival.

PMID- 18061263
TI  - Integrating evidence from neuroimaging and neuropsychological studies of
      obsessive-compulsive disorder: the orbitofronto-striatal model revisited.
AB  - Obsessive-compulsive disorder (OCD) is a common, heritable and disabling
      neuropsychiatric disorder. Theoretical models suggest that OCD is underpinned by
      functional and structural abnormalities in orbitofronto-striatal circuits.
      Evidence from cognitive and neuroimaging studies (functional and structural
      magnetic resonance imaging (MRI) and positron emission tomography (PET)) have
      generally been taken to be supportive of these theoretical models; however,
      results from these studies have not been entirely congruent with each other. With
      the advent of whole brain-based structural imaging techniques, such as voxel
      based morphometry and multivoxel analyses, we consider it timely to assess
      neuroimaging findings to date, and to examine their compatibility with cognitive
      studies and orbitofronto-striatal models. As part of this assessment, we
      performed a quantitative, voxel-level meta-analysis of functional MRI findings,
      which revealed consistent abnormalities in orbitofronto-striatal and other
      additional areas in OCD. This review also considers the evidence for involvement
      of other brain areas outside orbitofronto-striatal regions in OCD, the
      limitations of current imaging techniques, and how future developments in imaging
      may aid our understanding of OCD.

PMID- 18061268
TI  - Endothelial keratoplasty a simplified technique to minimize graft dislocation,
      iatrogenic graft failure, and pupillary block.
AB  - PURPOSE: Endothelial keratoplasty is an exciting alternative to full-thickness
      penetrating keratoplasty for replacing the diseased endothelium, yet 3 of the
      major complications seen are dislocation of the donor tissue, primary graft
      failure (PGF), and pupillary block from the residual, supportive air bubble.
      Surgical strategies were developed to reduce the likelihood of occurrence of
      these complications in our first 200 consecutive Descemet's stripping automated
      endothelial keratoplasty (DSAEK) cases. DESIGN: Prospective, noncomparative,
      interventional case series. PARTICIPANTS: Two hundred eyes of 172 patients with
      corneal edema. METHODS: An institutional review board-approved, prospective
      protocol of endothelial keratoplasty was initiated. Four different surgeons
      performed DSAEK for the initial 200 consecutive cases using a technique of
      peripheral recipient bed scraping for donor edge adherence and leaving a residual
      supportive air bubble, which was freely mobile, and <or=9 mm in diameter. The
      incidence of early postoperative complications was then determined. MAIN OUTCOME
      MEASURES: Postoperative donor graft dislocation, iatrogenic PGF, and pupillary
      block glaucoma. RESULTS: There were only 3 dislocations into the anterior chamber
      in this series of 200 consecutive eyes (1.5% dislocation rate) and all were
      successfully reattached with a second air bubble. There were no dislocations in
      the last 115 consecutive cases. There were two cases of donors that were attached
      but decentered in this series. There were no PGFs. There was not a single case of
      pupillary block in the entire series. CONCLUSION: The surgical technique
      described in this series, which utilized peripheral recipient bed scraping, has
      an acceptably low dislocation rate (1.5%) and yielded no cases of iatrogenic PGF.
      The complication of pupillary block was never seen in this series, likely due to
      our technique of utilizing a freely mobile, <or=9 mm residual air bubble at the
      conclusion of surgery.

PMID- 18061269
TI  - Diagnostic capability of scanning laser polarimetry with variable cornea
      compensator in Indian patients with early primary open-angle glaucoma.
AB  - PURPOSE: To evaluate the diagnostic ability of scanning laser polarimetry (GDx
      variable corneal compensator [VCC]) for early glaucoma in Asian Indian eyes.
      DESIGN: Cross-sectional observational study. PARTICIPANTS: Two groups of patients
      (early glaucoma and normal) who satisfied the inclusion and exclusion criteria
      were included. Early glaucoma was diagnosed in presence of open angles,
      characteristic glaucomatous optic disc changes correlating with the visual field
      (VF) on automated perimetry (VF defect fulfilling at least 2 of 3 Anderson and
      Patella's criteria with mean deviation >or= -6 decibels). Normal subjects had
      visual acuity >or= 20/30 and intraocular pressure < 22 mmHg, with a normal optic
      disc and fields and no ocular abnormality. METHODS: All patients underwent
      complete ophthalmic evaluation, including VF examination (24-2/30-2 Swedish
      interactive threshold algorithm standard program) and imaging with GDx VCC. MAIN
      OUTCOME MEASURES: Sensitivity, specificity, positive predictive value and
      negative predictive value, area under the receiving operating characteristic
      curve, and likelihood ratios (LRs) were calculated for various GDx VCC
      parameters. RESULTS: Seventy-four eyes (74 patients) with early glaucoma and 104
      eyes (104 normal subjects) were enrolled. TSNIT Std Dev (temporal-superior-nasal
      inferior-temporal standard deviation) had the best combination of sensitivity and
      specificity-61.3 and 95.2, respectively-followed by nerve fiber index score > 50
      (sensitivity, 52.7%; specificity, 99%). Nerve fiber index score > 50 had positive
      and negative predictive values of 74.3% and 97.6%, respectively, for an assumed
      glaucoma prevalence of 5%. Nerve fiber index score > 50 had a positive LR (+LR)
      of 54.8 for early glaucoma. CONCLUSIONS: GDx VCC has moderate sensitivity, with
      high specificity, in the diagnosis of early glaucoma. The high +LR for the nerve
      fiber index score can provide valuable diagnostic information for individual
      patients.

PMID- 18061270
TI  - Spectral-domain optical coherence tomography with multiple B-scan averaging for
      enhanced imaging of retinal diseases.
AB  - OBJECTIVE: To determine whether multiple B-scan averaging improves the quality of
      spectral-domain optical coherence tomography (SD OCT) images of the retina.
      DESIGN: Prospective cross-sectional study. PARTICIPANTS: One hundred one eyes of
      84 patients with various retinal diseases. METHODS: A prototype SD OCT system was
      used with a sensitivity of 98 decibels, air axial resolution of 6.1 mum, and
      acquisition rate of approximately 18 700 axial scans per second. To evaluate
      multiple B-scan averaging, a set of 12 B-scan images was obtained at the
      identical retinal location and the multiple scans were averaged using custom
      software; some images containing lateral eye motion were rejected. Objective
      differences in image quality were measured by comparing the contrast-to-noise
      ratios (CNRs) for key retinal structures in unenhanced and enhanced images using
      non-repeated-measures analysis of variance and the Dennett post hoc test.
      Subjective differences in image quality were evaluated by asking trained
      ophthalmologists independently to rank pairs of unenhanced and enhanced SD OCT
      images on a 5-point scale (upper or lower image definitely better, slightly
      better, or equal) and analyzing results using the Scheffe method for paired
      comparisons. MAIN OUTCOME MEASURES: Contrast-to-noise ratio in enhanced versus
      unenhanced SD OCT images, expert comparison of image quality, and retinal
      pathologic features in enhanced versus unenhanced SD OCT images. RESULTS:
      Averaging >4 SD OCT scans achieved significant improvement in CNR and also
      improved ophthalmologists' ability to distinguish retinal structures. More than 4
      scans could be averaged for 100 (99%) of the 101 eyes with retinal diseases in
      this study. Averaging >4 SD OCT scans improved visualization of structures, such
      as abnormalities in the photoreceptor layer and sub-retinal pigment epithelium
      (RPE) lesions, that could not be identified clearly in single-scan SD OCT images
      because of various retinal pathologic features. These included intraretinal
      lesions that mask the underlying structures, such as cystoid macular edema and
      retinal hemorrhage, and inward shifting of the sensory retina because of pigment
      epithelial detachment and lesions beneath the RPE. CONCLUSIONS: Multiple B-scan
      averaging is an easy and practical method to improve the quality of retinal
      images obtained by SD OCT and thereby to improve the diagnosis and management of
      retinal diseases.

PMID- 18061271
TI  - Supplementary intracameral lidocaine for phacoemulsification under topical
      anesthesia. A meta-analysis of randomized controlled trials.
AB  - TOPIC: We consider a meta-analysis of randomized controlled trials (RCTs)
      comparing topical anesthesia alone with topical and intracameral anesthesia for
      phacoemulsification. CLINICAL RELEVANCE: Topical anesthesia has become an
      increasingly popular option for day-case cataract surgery. Many surgeons now use
      supplementary intraoperative intracameral lidocaine, but the evidence base for
      the supplementary use of intracameral anaesthetic during cataract surgery has
      never been reviewed systematically. METHODS/LITERATURE REVIEWED: The primary
      objective is to compare intraoperative pain for phacoemulsifications under
      topical anesthesia with and without intracameral anesthesia. The secondary
      objectives are to assess both adverse effects and complications attributable to
      choice of anesthesia and the need for additional anesthesia during surgery.
      Searches were made from the Cochrane Central Register of Controlled Trials,
      Medline, Excerpta Medica database, and Latin American and Caribbean Health
      Science Information Database up to and including June 8, 2006. RESULTS: Eight
      RCTs, recruiting a total of 1281 patients, were identified. Our data comparison
      showed significantly lower intraoperative pain perception in patient groups using
      supplementary intracameral lidocaine. No significant difference in intraoperative
      adverse events, corneal toxicity, or the need for supplemental anesthesia was
      identified. CONCLUSION: Intraoperative pain during cataract surgery under topical
      anaesthetic is reduced by intracameral lidocaine. Possible adverse effects of
      intracameral lidocaine cannot be excluded due to significant heterogeneity in
      outcome measures between different RCTs. Although a statistically significant
      reduction in intraoperative pain has been demonstrated, it is not yet possible to
      recommend this additional intervention without reservations.

PMID- 18061272
TI  - Potentiometric, spectrophotometric and calorimetric study on iron(III) and
      copper(II) complexes with 1,2-dimethyl-3-hydroxy-4-pyridinone.
AB  - The iron(III)-1,2-dimethyl-3-hydroxy-4-pyridinone (Deferiprone) system is
      carefully characterized by a combined potentiometric-spectrophotometric procedure
      at 25 and 37 degrees C at different ionic strengths, and by thermochemical and
      quantum-chemical studies. The main purpose of this work was to determine how the
      temperature dependence of both complex-formation and protonation constants can
      affect the pFe values on going from 25 degrees C (pFe is normally calculated
      using 25 degrees C stability constants) to the physiological temperature of 37
      degrees C at which chelating agents are active in vivo. The copper(II)
      Deferiprone system is also studied and the iron(III)-Deferiprone distribution
      diagrams in presence of variable copper(II) amounts are shown so as to explain
      possible side effects due to a competing metal ion during the chelating therapy
      of iron overload.

PMID- 18061273
TI  - Validation of a fiducial-based atlas localization method for deep brain
      stimulation contacts in the area of the subthalamic nucleus.
AB  - Differences in the location of active contacts with respect to the subthalamic
      nucleus (STN) may account for much variability in motor, psychiatric and
      cognitive responses to deep brain stimulation (DBS) in Parkinson disease (PD)
      patients. Because localization of STN based on hypointensity in T2-weighted MR
      images is unreliable and further limited by artifacts from the metal electrodes,
      we developed and validated a method to transform brain images into stereotactic
      space [Mai JK, Assheuer J, Paxinos G. Atlas of the Human Brain, 2nd ed. San
      Diego: Elsevier Academic; 2004] using reliably-identified anatomic fiducials
      identified in high-resolution T2-weighted pre-operative MR images. Average
      intraclass correlation between two raters for 29 PD patients was 0.93 for those
      fiducials used to define the atlas. Accuracy of the registration was tested by
      comparing the rater-identified centers of the red nuclei with their predicted
      locations from the fiducial-based atlas transformation. Mean discrepancies were
      0.1, 0.9, and 0.0mm (x, y, z) with standard deviations of 0.9, 0.7 and 1.1mm,
      respectively. Because post-operative determination of contact location with
      respect to the STN is necessary due to possible shifting of electrodes during
      surgical placement, we identified active contacts on post-operative CT images and
      transformed their locations into stereotactic space. This method provides an
      accurate and reliable means for STN DBS contact localization.

PMID- 18061274
TI  - Challenge by the murine brain: multi-pinhole SPECT of 123I-labelled
      pharmaceuticals.
AB  - This protocol presents an improved method for SPECT imaging based on multi
      pinhole techniques, applied to the visualisation of neurotracers in small animal
      models. Three types of collimators with 6-pinhole apertures adapted to special
      requirements for the imaging of the brain of mice and rats and to full body
      imaging in mice are employed in the experiments. A conventional triple-headed
      TRIAD/Trionix SPECT system was upgraded with pyramidal supports and shieldings
      onto the multi-pinhole collimators were installed. The system was employed for
      the assessment of the uptake of [123I]FP-CIT and [123I]IBZM, well known tracers
      of dopamine transport and dopamine D2/D3 receptors, respectively. Requirements
      regarding the applied radioactivity are reported, as well as further conditions
      determining the effectiveness of the detection of the uptake of [123I]FP-CIT and
      [123I]IBZM. The measurements in mice required only 20-25% of the activity
      described in previous studies. Dynamic measurements are presented, with a time
      resolution as high as 10 min in the brain of rats. Due to the lower signal
      intensity obtained for mice, the time resolution was 42min for [123I]FP-CIT, with
      a ratio ROI/background of 5.4, and 17 min for [123I]IBZM, with the ratio
      ROI/background of 4.5 (1.6-7.4).

PMID- 18061275
TI  - Mechanomyographic amplitude and mean power frequency responses during isometric
      ramp vs. step muscle actions.
AB  - The purpose of the present study was to compare the mechanomyographic amplitude
      (MMG(RMS)) and mean power frequency (MMG(MPF)) vs. torque relationships during
      isometric ramp and step muscle actions for the vastus lateralis (VL) and rectus
      femoris (RF) muscles. Nineteen subjects (mean+/-S.D. age=24+/-4 years) performed
      2 isometric maximal voluntary contractions (MVCs) before and after 2 or 3
      isometric ramp muscle actions from (5-95% MVC) to 9 submaximal step muscle
      actions (15, 25, 35, 45, 55, 65, 75, 85, and 95% MVC). MMG signals were recorded
      from the VL and RF muscles, and MMG(RMS) and MMG(MPF) values were computed for
      each corresponding percentage of the MVC. Absolute and normalized MMG(RMS) and
      MMG(MPF) vs. torque relationships were analyzed and interpreted on a subject-by
      subject and composite pattern basis using polynomial regression and repeated
      measures ANOVAs. For MMG(RMS) and MMG(MPF), only 16-53% and 11-26% of the
      individual responses were consistent with the composite polynomial models,
      respectively. In addition, the normalized composite MMG(RMS) values were greater
      for the RF than the VL from 35 to 85% MVC. Only 47% of the MMG(RMS) and 5% of the
      MMG(MPF) individual patterns of responses were the same for the ramp and step
      muscle actions, and differences were also observed for the composite MMG(RMS) and
      MMG(MPF) patterns between the ramp and step muscle actions. Overall, these
      findings indicated that the torque-related patterns of responses for MMG(RMS) and
      MMG(MPF) were different among subjects (i.e., inter-individual variability) and
      were muscle- (VL vs. RF) and mode-specific (ramp vs. step).

PMID- 18061276
TI  - Speed of action: the relative efficacy of short psychodynamic supportive
      psychotherapy and pharmacotherapy in the first 8 weeks of a treatment algorithm
      for depression.
AB  - OBJECTIVE: To examine the efficacy and speed of action of short-term
      psychodynamic supportive psychotherapy (SPSP) in comparison to pharmacotherapy
      (PhT) in the acute treatment of depression. METHOD: This study reported on the
      first 8 weeks of a treatment algorithm for depression. 70 patients with a
      depressive episode according to DSM-IV were randomized to PhT, 71 patients were
      randomized to SPSP. The acceptability of the psychotherapy was greater than
      pharmacotherapy. RESULTS: At the end of the first 8 weeks of treatment, attrition
      rates were similar in both conditions. PhT-patients were better off at 4 weeks
      according to two of the four measures The superiority of PhT was clearer on the
      self-report than on the independent measure. CONCLUSIONS: There are signs that
      the benefits of PhT over SPSP--where detected--are short-lived and cover mostly
      the first month of treatment. The progression of these patients through the rest
      of their treatments, and afterwards, will be reported in further contributions.

PMID- 18061277
TI  - Transportation stress alters the circulating steroid environment and neutrophil
      gene expression in beef bulls.
AB  - Stress and its association with altered immune function and incidence of
      respiratory diseases in cattle have lead to concerns over animal health and
      welfare during truck transportation. Previously, bulls subjected to
      transportation stress displayed altered expression of candidate neutrophil genes,
      warranting a broader investigation of the neutrophil transcriptome and possible
      associations with fluctuations in circulating steroid hormones. In the current
      study, blood was collected from six Belgian BluexFriesian bulls at -24, 0, 4.5,
      9.75, 14.25, 24, and 48h relative to initiation of 9h of truck transportation.
      Plasma concentrations of cortisol, dehydroepiandrosterone (DHEA), progesterone,
      and testosterone were measured; cortisol:DHEA ratios were computed. Neutrophil
      gene expression was monitored by microarray analysis using bovine immunobiology
      (BOTL-5) microarrays. Eighty-eight genes were identified as being differentially
      expressed at P<0.05. Putatively affected genes were grouped into ontological
      clusters; those of greatest interest for qRT-PCR validation were involved in
      immune response, apoptosis, wound healing, and several of currently unknown
      function. Confirmed gene expression changes supported the dramatic effects of
      transportation stress on the bovine neutrophil transcriptome. Temporal
      correlations between gene expression profiles and circulating total leukocyte and
      neutrophil counts were apparent. However, few relationships between gene
      expression and plasma steroid profiles were detected, possibly due to the
      biological time-lag between these variables not captured by the blood collection
      schedule. Further investigation into the factors underlying neutrophil gene
      expression changes and validations at the protein and cell behavior levels will
      lead to a better understanding of altered innate immunity in cattle during
      transportation stress.

PMID- 18061278
TI  - Characterization of monoclonal antibodies to equine interleukin-10 and detection
      of T regulatory 1 cells in horses.
AB  - Interleukin-10 (IL-10) terminates inflammatory immune responses and inhibits
      activation and effector functions of T-cells, monocytes, macrophages and
      dendritic cells. IL-10 has also been found to be a key cytokine expressed by
      subpopulations of regulatory T-cells. In this report, we describe the generation
      and characterization of three monoclonal antibodies (mAbs) to equine IL-10. The
      antibodies were found to be specific for equine IL-10 using different recombinant
      equine cytokine/IgG fusion proteins. Two of the anti-equine IL-10 mAbs were
      selected for ELISA to detect secreted IL-10 in supernatants of mitogen stimulated
      equine peripheral blood mononuclear cells (PBMC). The sensitivity of the ELISA
      for detecting secreted IL-10 was found to be around 200pg/ml. The production of
      intracellular IL-10 was measured in equine PBMC by flow cytometry. PBMC were
      stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin in the
      presence of the secretion blocker Brefeldin A. All three anti-IL-10 mAbs detected
      a positive population in PMA stimulated lymphocytes which was absent in the
      medium controls. Around 80% of the IL-10(+) cells were CD4(+). Another 15% were
      CD8(+) cells. Double staining with IL-4 or interferon-gamma (IFN-gamma) indicated
      that PMA and ionomycin stimulation induced 80% IL-10(+)/IFN-gamma(+) lymphocytes,
      while only 5% IL-10(+)/IL-4(+) cells were observed. By calculation, at least 60%
      of the IL-10(+)/IFN-gamma(+) cells were CD4(+) lymphocytes. This expression
      profile corresponds to the recently described T regulatory 1 (T(R)1) cell
      phenotype. In summary, the new mAbs to equine IL-10 detected native equine IL-10
      by ELISA and flow cytometry and can be used for further characterization of this
      important regulatory cytokine in horses.

PMID- 18061279
TI  - BDNF A196G and C270T gene polymorphisms and susceptibility to multiple sclerosis
      in the Polish population. Gender differences.
AB  - Two single nucleotide polymorphisms of the human BDNF gene, G196A and C270T, and
      their impact on the susceptibility to MS and disease progression in the Polish
      population were investigated. Increased risk of the disease was found for 196G/G
      carriers (OR -- 1.63, p=0.01) (only females) and 270C/T carriers (OR -- 7.76,
      p<0.001) (both males and females). The first signs of the disease appeared
      earlier in 196G/G than 196G/A patients (p=0.01), but it was limited to males. Our
      results show that C270T and G196A BDNF polymorphisms may affect susceptibility to
      and onset of MS, but further verification is needed, with special attention to
      gender differences.

PMID- 18061280
TI  - Differential cerebro spinal fluid proteome investigation of Leber hereditary
      optic neuropathy (LHON) and multiple sclerosis.
AB  - Leber's hereditary optic neuropathy (LHON) is a genetic disease leading to the
      loss of central vision and optic nerve atrophy. The existence of occasional cases
      of LHON patients developing a Multiple Sclerosis (MS)-like illness and the
      hypothesis that mtDNA variants may be involved in MS suggest the possibility of
      some common molecular mechanisms linking the two diseases. We have pursued a
      comparative proteomics approach on cerebrospinal fluid (CSF) samples from LHON
      and MS patients, as well as healthy donors by employing 2-DE gel separations
      coupled to MALDI-TOF-MS and nLC-MS/MS investigations. 7 protein spots showed
      significant differential distribution among the three groups. Both CSF of LHON or
      MS patients are characterized by lower level of transthyretin dimer adduct while
      a specific up regulation of Apo A-IV was detected in LHON CSF.

PMID- 18061281
TI  - Papillary thyroid carcinoma in a 3-year-old child: case report.
AB  - Thyroid cancers account for 0.5-3.0% of all childhood malignancies. These cancers
      are exceedingly rare at ages younger than 5 years. Although the disease is
      biologically more aggressive in children when compared with adults, the prognosis
      is better. There are only few case reports in the literature describing papillary
      thyroid carcinoma under age 5. In this case report, a 3-year-old child with
      bilateral multiple masses on the neck that were present for 6 months and who was
      diagnosed with thyroid papillary carcinoma is presented, and the diagnosis and
      therapy of the disease is discussed.

PMID- 18061282
TI  - Rotaviral RNA found on various surfaces in a hospital laundry.
AB  - The aim of this investigative study was to determine the presence of rotaviral
      RNA at various control points (CP) of a hospital laundry. One of the possible
      sources of hospital infections is inappropriately laundered and disinfected
      hospital textiles. RT-PCR and nested PCR for gene amplification using specific
      primers following RNA isolation were used to determine the presence of rotaviral
      RNA on swabs. In addition, rotavirus suspensions were inoculated on marked
      surfaces as positive controls for different surfaces (cotton textiles, folding
      table and industrial dryer). Rotaviral RNA was found on various laundry surfaces:
      technical equipment, storage shelves, transport vehicles, personnel's hands, damp
      textiles, and folded laundry. Rotaviral RNA was also detected at all positive
      controls on tested surfaces after 24h. Based on the results, it is very important
      to take into consideration the proper handling of textiles after washing as one
      of the precautions against hospital-acquired infections. This paper reports the
      presence of rotaviral RNA for the first time on surfaces in laundries and
      equipment, as well as textiles.

PMID- 18061283
TI  - NIAID resources for developing new therapies for severe viral infections.
AB  - Severe viral infections, including hemorrhagic fever and encephalitis, occur
      throughout the world, but are most prevalent in developing areas that are most
      vulnerable to infectious diseases. Some of these can also infect related species
      as illustrated by the threatened extinction of gorillas by Ebola infection in
      west and central Africa. There are no safe and effective treatments available for
      these serious infections. In addition to the logistical difficulties inherent in
      developing a drug for infections that are sporadic and occur mainly in the third
      world, there is the overwhelming barrier of no hope for return on investment to
      encourage the pharmaceutical industry to address these unmet medical needs.
      Therefore, the National Institute of Allergy and infectious Disease (NIAID) has
      developed and supported a variety of programs and resources to provide assistance
      and lower the barrier for those who undertake these difficult challenges. The
      primary programs relevant to the development of therapies for severe viral
      infections are described and three case studies illustrate how they have been
      used. In addition, contact information for accessing these resources is supplied.

PMID- 18061284
TI  - Prucalopride and donepezil act synergistically to reverse scopolamine-induced
      memory deficit in C57Bl/6j mice.
AB  - It is known that 5-HT(4) receptor agonists increase sAPPalpha levels in the
      cortex and hippocampus of mice as well as in a model of Alzheimer's disease (AD).
      As sAPPalpha is thought to have pro-mnesic properties, we assessed whether its
      increase induces cognitive improvement in a spatial memory task and whether it
      reverses a scopolamine-induced memory deficit. Mice treated or not treated with
      scopolamine were trained in the Morris water maze for 3 days. Before the probe
      test, they received an injection of either a 5-HT(4) receptor agonist
      (prucalopride or RS 67333), or an acetylcholinesterase inhibitor (donepezil), or
      both drugs. As expected, scopolamine decreased performance, an effect that was
      not reversed by the drugs tested when injected alone. However, prucalopride (5 mg
      kg(-1), s.c.) acted synergistically with donepezil (0.75 mg kg(-1), s.c.) to
      counteract completely scopolamine-induced amnesia. Western blot analysis of
      tissue homogenates in the cortex and hippocampus shows that sAPPalpha levels did
      not differ between saline- and scopolamine-treated mice. Furthermore, a region
      dependent drug action was observed since the scopolamine-treated mice display a
      tendency to increase sAPPalpha levels in the hippocampus after donepezil or in
      the cortex after prucalopride. Our results suggest that a combined treatment with
      a 5-HT(4) receptor agonist with an acetylcholinesterase inhibitor has beneficial
      effects on memory in mice. Moreover, it seems to enhance sAPPalpha levels in two
      brain regions highly affected in AD. Thus, a drug polytherapy could be
      interesting not only to enhance cognitive performance and decrease drawbacks but
      also to get the best action in each brain region.

PMID- 18061285
TI  - Chronic ethanol consumption in rats produces residual increases in anxiety 4
      months after withdrawal.
AB  - The present study investigated the long-term effects of ethanol consumption in
      rats. Subjects were maintained on either an ethanol (alcohol) (2.7-6.7%, v/v) or
      an isocaloric liquid control diet for 26 consecutive days (M=13.7 g/kg/day).
      Testing for working memory was conducted in a Morris water maze (2 trials/day for
      8 days) and commenced after either a short (19 days) or long (120 days)
      abstinence period. This was followed by assessment of 72 h retention of passive
      avoidance. Animals were killed either 41 (short abstinence) or 152 days (long
      abstinence) post-ethanol and their brains stained with cresyl violet. Assessments
      of dorsal-ventral and medial-lateral cortical vertices were measured in sections
      derived from eight coronal planes extending +4.20 to -4.16 mm from Bregma.
      Results indicated that subjects in the ethanol/long abstinence group exhibited
      increased state anxiety due to their propensity to be thigmotaxtic (i.e., wall
      hugging) in the water maze. Unfortunately, such a swim pattern precluded
      assessment of working memory in our subjects. No evidence of ethanol-induced
      memory decrements were observed on retention of passive avoidance. There was some
      evidence that animals in the ethanol/long abstinent group suffered cortical
      thinning and slight compression of the CA1 layer within the hippocampus, although
      age might have contributed to the former effect. It was concluded that chronic
      ethanol consumption increases anxiety even after an extended period of withdrawal
      and may conspire with age to affect cortical integrity.

PMID- 18061286
TI  - Age-related changes in conditioned flavor preference in rats.
AB  - Age-related changes have been documented in regions of the brain shown to process
      reward information. However, few studies have examined the effects of aging on
      associative memory for reward. The present study tested 7- and 24-month-old rats
      on a conditioned flavor preference task. Half of the rats in each age group
      received an unsweetened grape-flavored solution (CS-) on odd-numbered days and a
      sweetened cherry-flavored solution (CS+) on even-numbered days. The remaining
      rats in each age group received a sweetened grape-flavored solution (CS+) on odd
      numbered days and an unsweetened cherry-flavored solution (CS-) on even-numbered
      days. During the acquisition phase of testing, the designated solution (CS+ or CS
      ) was presented to each rat for 15 min daily across six consecutive days. On the
      preference phase, each rat received unsweetened cherry and unsweetened grape
      flavored solutions simultaneously for 15 min daily across four consecutive days.
      The 7-month-old rats showed a significant preference for the flavor that was
      previously sweetened during the acquisition phase (CS+) compared to the
      previously unsweetened solution (CS-) when the two unsweetened solutions were
      presented simultaneously during the preference phase of testing. In contrast, the
      24-month-old rats did not show a preference and consumed roughly equal amounts of
      the previously sweetened (CS+) and unsweetened (CS-) solutions. Thus, the data
      suggest that the ability to form flavor-reward associations declines with
      increasing age, resulting in impaired conditioned flavor preference.

PMID- 18061287
TI  - Identification of novel bradyzoite-specific Toxoplasma gondii genes with domains
      for protein-protein interactions by suppression subtractive hybridization.
AB  - By using suppression subtractive hybridization we identified five so far
      uncharacterized stage specific genes in Toxoplasma gondii, which are induced
      during tachyzoite-to-bradyzoite differentiation. The mRNA level of a putative
      zinc-finger protein was increased 23-fold in bradyzoites, while the remaining
      four genes displayed induction levels >100-fold. Two of these genes predict
      proteins with domains for protein-protein interactions. One protein (ANK1)
      contains both, a TPR-domain and an ankyrin motif, which consists of seven
      repeats. ANK1 was shown by epitope tagging experiments to be localized in the
      cytosol. In a fraction of parasites, the myc-tagged fusion protein was
      additionally localized in the nucleus, which is in agreement with the presence of
      a bipartite nuclear targeting sequence in ANK1. The identification of bradyzoite
      specific proteins with TPR- and ankyrin-domains supports the concept that during
      stage conversion a variety of proteins which are involved in protein-protein
      interactions are induced, thereby assisting the rebuilding of the proteome.

PMID- 18061288
TI  - Loss of actin does not affect export of newly synthesized proteins to the surface
      of Trypanosoma brucei.
AB  - Vesicle traffic to and from the surface is highly polarized in African
      trypanosomes. Actin is required for polarized endocytic traffic in bloodstream
      forms of African trypanosomes but its role in other pathways has remained
      equivocal. A combination of metabolic pulse chase labelling and surface
      biotinylation during the chase period along with the use of conditional RNA
      interference was employed to demonstrate that substantial loss of actin had no
      effect on the export of newly synthesized proteins to the surface of bloodstream
      and procyclic forms of Trypanosoma brucei. These results indicated that this
      trafficking pathway to the surface operates as normal even when actin levels are
      significantly lower than normal and endocytic activity is abolished. Taken
      together the data support the view that the secretory and endocytic pathways are
      not obligatorily coupled.

PMID- 18061289
TI  - Validation study of a social functioning scale: The social-SMAF (social
      Functional Autonomy Measurement System).
AB  - This article aims to describe the validation studies of a social functioning
      scale developed recently to be possibly added to the SMAF. One hundred and one
      older adults presenting moderate to severe disabilities and living in two long
      term care institutions (LTCI) participated in the validation studies. For the
      interrater reliability, 51 participants were assessed by two different nurses 24
      72 h apart whereas for the test-retest reliability (n=50), they were evaluated
      twice by the same nurse within a 7-day interval. Convergent validity was verified
      (n=74) by comparing the new subscale with questionnaires of functional status
      (Older American Resources and Services, OARS), social participation (Assessment
      of Life Habits, Assessment of LIFE-H) and social support (Social Provisions
      Scale, SPS). The interrater reliability and test-retest study showed,
      respectively, good mean agreement percentages (84% and 85%) as well as good or
      excellent intraclass correlation coefficients (ICCs) (0.78; 95% confidence
      interval (CI): 0.64-0.87 and 0.96; CI: 0.93-0.98). The social-SMAF demonstrated
      significant correlations with the OARS (r=-0.42), LIFE-H (r=-0.31) and SPS (r=
      0.49). These results suggest that the new subscale is a reliable and valid tool
      for assessing social functioning autonomy of the older adult.

PMID- 18061290
TI  - Anxiety and depression among the patients with frequent implantable cardioverter
      defibrillator discharges.
AB  - We examined 16 patients, aged 24 to 73, with ICD. Condition of qualification to
      the examined group was experiencing many discharges (from 25 to above 200) or
      electric shock (3 or more discharges following one after another). Most of the
      patients (14) were afraid of ICD discharges. 11 patients presented
      psychopathological symptoms: 7 anxiety disorders (3 patients who underwent storm
      presented acute and posttraumatic stress disorders) and 4 depression. Some
      actions for reduction of risk of psychopathological disorders in patients
      experienced ICD discharges should be taken: performing RF ablation as soon as
      possible after first shocks and creation of the system of psychological and
      psychiatric help for patients with ICD.

PMID- 18061292
TI  - Blood pressure control in the year following coronary events.
AB  - BACKGROUND: Blood pressure control is often insufficient in secondary prevention.
      The objective of the present study was to determine predictors for long-term
      elevated blood pressure (BP) in patients after coronary events. METHODS: Patients
      were included at admission to inpatient cardiac rehabilitation. A total of 18
      cardiac rehabilitation centers in Germany participated. Indications for admission
      were myocardial infarction (MI), coronary artery bypass grafting (CABG), or
      percutaneous transluminal coronary angioplasty (PTCA). The duration of follow-up
      was 12 months. Risk factors, medication, and clinical events were assessed from
      patients and their physicians. RESULTS: A consecutive sample of 1907 men (mean
      age 60+/-10 years) and 534 women (mean age 65+/-10 years) was admitted; the 12
      month follow-up rate was 85%. Of all patients, 38% had a BP > or =140 and/or > or
      =90 mmHg at admission to the rehabilitation center compared to 48% at the 12
      month follow-up. Patients with diabetes were less likely to achieve BP <140/90
      mmHg compared to patients without diabetes (43% vs. 56%; P<0.001). In
      multivariable analyses, significant predictors for elevated BP after 12 months
      were baseline BP > or =140/90 mmHg (RR 2.5; 95% CI 1.7, 3.7), diabetes (RR 2.2;
      95% CI 1.4, 3.5), and indication for admission (MI vs. CABG RR 0.6; 95% CI 0.4,
      1.0, and PTCA vs. CABG RR 0.5; 95% CI 0.2, 1.0). CONCLUSIONS: Long-term blood
      pressure control is not satisfactory in about half of the patients following
      coronary events. Particularly, patients with diabetes appear to be at risk for
      elevated blood pressure.

PMID- 18061291
TI  - Cardiovascular magnetic resonance characterization of a hamartoma in an
      asymptomatic child.
AB  - BACKGROUND: The prevalence of primary cardiac neoplasms is approximately 0.3% and
      these masses should be distinguished from many of other primary and secondary
      processes that can occur in the heart. Further assessment of the left ventricular
      mass presents important clinical implications. Cardiovascular magnetic resonance
      was used. CLINICAL CASE: An asymptomatic 12-year-old child was referred for
      cardiovascular magnetic resonance imaging to further assess a left ventricular
      mass found after an echocardiography, executed for assessment for sport activity.
      His past medical history was absolutely negative. The patient was in optimal
      state of health. The EKG showed an aspecific ST elevation. A hamartoma was
      diagnosed. A surgical approach was performed. After 7 days the patient is in good
      condition.

PMID- 18061294
TI  - Dose painting with IMPT, helical tomotherapy and IMXT: a dosimetric comparison.
AB  - PURPOSE: A planning study is presented in order to compare the suitability of
      intensity modulated photon radiotherapy (IMXT), helical tomotherapy (HTT) and
      intensity modulated protontherapy (IMPT) for dose painting. METHODS: For three
      HNC patients, nine different treatment plans were generated. Firstly, a uniform
      dose escalation (uniDE) of 10% was applied to the FDG PET positive region with
      step-and-shoot IMXT, HTT and IMPT. Secondly, dose painting by numbers (DPBN) was
      performed based on dose escalation maps determined from dynamic FMISO PET data
      for all three treatment modalities. Thirdly, the maximum PTV dose was not
      constrained while maximizing TCP, whereas the same organ at risk constraints as
      used for conventional IMXT had to be fulfilled. The dose distributions in spinal
      cord and parotids were optimized with equivalent uniform dose (EUD) constraints,
      expressing the risk of late reactions. RESULTS: The target coverage obtained with
      IMPT and HTT was more conformal regarding the inhomogeneous prescriptions than
      with IMXT for both uniDE and DPBN. IMPT allowed significantly higher levels of
      sparing normal tissues. In addition, the study showed that using IMXT, HTT or
      IMPT theoretically allows dose escalations of up to 50% under late reaction iso
      toxicity conditions. CONCLUSION: The quality of dose painting treatment plans
      created for IMXT, HTT and IMPT is comparable. More accurate target coverage can
      be reached with HTT and IMPT, whereas IMPT allows to significantly reduce the
      dose to normal tissues.

PMID- 18061296
TI  - An investigation of sources of Campylobacter in a poultry production and packing
      operation in Barbados.
AB  - Chicken meat is frequently contaminated with Campylobacter jejuni and is thought
      to be the major source of organisms causing human Campylobacter enteritis.
      Genotypic similarities between Campylobacter isolates from chicken meat at retail
      outlets and patients with gastroenteritis in Barbados suggested that it is a
      vehicle for infection of humans on the island and prompted this investigation of
      transmission of Campylobacter in a local poultry operation. Campylobacter testing
      was conducted at the hatchery, on the broiler farm and in the processing plant
      for two consecutive production cycles. The genetic relatedness of Campylobacter
      isolates was determined by RAPD typing with primer OPA 11. Hatchery samples and
      week-old chicks were negative for Campylobacter. Flocks became colonized as early
      as three weeks after introduction to the farm. Ten distinct RAPD genotypes were
      identified among isolates. Some genotypes were similar and may be of clonal
      origin. There was no evidence of vertical transmission of Campylobacter. The
      results suggest that the broiler flock was infected from more than one source in
      the farm environment.

PMID- 18061295
TI  - Detection, quantification and vitality of Listeria monocytogenes in food as
      determined by quantitative PCR.
AB  - In this paper we describe the development of a quantitative PCR (qPCR) technique
      to detect, quantify and determine the vitality of Listeria monocytogenes in
      foods. The method was based on the amplification of the intergenic region spacer
      (IGS) between the 16S and 23S rRNA genes. A panel of more than 100 strains of
      Listeria spp. and non-Listeria was used in order to verify the specificity of the
      primers and Taqman probe and amplification signals were obtained only when L.
      monocytogenes DNA and RNA were loaded in the qPCR mix. Standard curves were
      constructed in several food matrices (milk, meat, soft cheese, fermented sausage,
      cured ham and ready-to-eat salad). The quantification limit was of 10(3)-10(4)
      cfu/g or ml, while for the determination of vitality it was 10(4)-10(5) cfu/g or
      ml. After an overnight enrichment in BHI at 37 degrees C also 10 cfu/g or ml
      could be detected in all the matrices used in this study. When we applied the
      protocol to food samples collected from the market or from small food processing
      plants, on a total number of 66 samples, 4 fresh cheeses from raw milk gave
      positive results prior to the overnight incubation, while 9 samples, of which
      only one represented by fresh meat and the others by cheeses from raw milk, were
      positive after the enrichment. Out of the 4 positive samples, only one could be
      quantified and it was determined to contain 4x10(3) cfu/g.

PMID- 18061297
TI  - Immunomodulatory effect of halophilic lactic acid bacterium Tetragenococcus
      halophilus Th221 from soy sauce moromi grown in high-salt medium.
AB  - A halophilic lactic acid bacterium, Tetragenococcus halophilus, was found to
      possess an immunomodulatory activity that promotes T helper type 1 (Th1) immunity
      in addition to its important roles in soy sauce brewing. Strain Th221 was
      selected from 151 strains isolated from soy sauce (shoyu) moromi, since it
      induced strong interleukin (IL)-12 production by mouse peritoneal macrophages in
      vitro. The relationship between the salt concentration in the medium and the IL
      12 production-inducing activity of this strain was investigated, and the activity
      was found to be strong when the bacteria were grown in medium containing > or
      =10% (w/v) salt. The Th1-promoting activity was also manifested in an in vivo
      mouse study, since Th1-dependant contact sensitivity was augmented and Th2
      immunity, as evaluated by specific immunoglobulin E production, was suppressed
      following oral ingestion of Th221. Based on these findings, Th221 administration
      may be useful for improving allergic symptoms.

PMID- 18061298
TI  - A new nitrilase from Bradyrhizobium japonicum USDA 110. Gene cloning, biochemical
      characterization and substrate specificity.
AB  - A nitrilase gene blr3397 from Bradyrhizobium japonicum USDA110 was cloned and
      over-expressed in Escherichia coli, and the encoded protein was purified to give
      a nitrilase with a single band of about 34.5kD on SDS-PAGE. The molecular weight
      of the holoenzyme was about 340kD as determined by light scattering analysis,
      suggesting that nitrilase blr3397 self-aggregated to an active form with the
      native structure being a decamer. The V(max) and K(m) for phenylacetonitrile were
      3.15U/mg and 4.36mM, respectively. The catalytic constant k(cat) and specificity
      constant k(cat)/K(m) were 111min(-1) and 2.6x10(4)min(-1)M(-1). This nitrilase is
      most active toward the hydrolysis of hydrocinnamonitrile among the tested
      substrates (4.3 times that of phenylacetonitrile). The nitrilase blr3397 shows
      higher activity towards the hydrolysis of aliphatic nitriles than that for the
      aromatic counterparts, and can be characterized as an aliphatic nitrilase in
      terms of activity. This nitrilase also possesses distinct features from the
      nitrilase bll6402 of the same microbe.

PMID- 18061299
TI  - System cell engineering by multi-scale manipulation.

PMID- 18061300
TI  - Computational prediction and identification of dengue virus-specific CD4(+) T
      cell epitopes.
AB  - In this study, we tried to identify dengue virus-specific CD4(+) T-cell epitopes,
      which can induce PBMC (peripheral blood mononuclear cells) isolated from DF
      convalescent patients (dengue virus type 1 infection) to secrete IFN-gamma. PBMC
      of DF convalescent patients were stimulated in vitro with dengue virus-derived
      peptides, which were prepared based on the prediction of dengue virus-specific
      CD4(+) T-cell epitopes by using RANKpep online software. Subsequently, the
      frequency of IFN-gamma producing T cells and percentage of IFN-gamma(+) CD4(+) T
      cells were measured by using ELISPOT assay and ICS assay (intracellular cytokine
      straining), respectively. The positive response of PBMC by ELISPOT showed that
      the numbers of SFC (spots forming cells) ranged from 50 to 310 SFC/1x10(6) PBMC.
      The positive response of PBMC by ICS assay showed that the percentage of IFN
      gamma(+) CD4(+) T cells ranged from 0.03 to 0.27%. As a result, C(45-57)
      (KLVMAFIAFLRFL), E(396-408) (SSIGKMFEATARG), NS3(23-35) (YRILQRGLLGRSQ), and
      NS3(141-155) (NREGKIVGLYGNGVV) were identified as dengue virus-specific CD4(+) T
      cell epitopes.

PMID- 18061301
TI  - Biorelevant dissolution testing of colon-specific delivery systems activated by
      colonic microflora.
AB  - The fermentation of non-starch polysaccharides by colonic microflora is popular
      as a triggering mechanism to achieve colon-specific drug delivery in that the
      existence of colonic microflora is independent of gastrointestinal transit time,
      pH, and disease conditions, and various delivery systems were developed using
      this strategy. One of such delivery systems, COLAL technology, has advanced into
      late stage of product development. However, in vitro characterization of these
      delivery systems remains a challenge in part because the critical performance
      indicator is colonic specificity of drug release. Moreover, the dynamic and
      ecologically diverse features of the colon are difficult to be incorporated into
      USP dissolution methods. As a result, alternative dissolution approaches have
      been designed to better represent the colonic conditions, such as utilizing
      polysaccharide-degrading enzymes, rat caecal contents, human fecal slurries, and
      multi-stage culture systems. The primary focus of this article is to summarize
      and review the dissolution testing currently used in characterizing colon
      specific delivery systems activated by microflora. A brief description of
      physiological parameters of the colon relevant to colonic drug release is also
      presented.

PMID- 18061302
TI  - Biodegradable particle formation for drug and gene delivery using supercritical
      fluid and dense gas.
AB  - Recent developments in biodegradable particle formation using supercritical
      fluids and dense gases have been reviewed with an emphasis on studies of
      micronizing and encapsulating poorly-soluble pharmaceuticals and gene. General
      review articles published in previous years have then been provided. A brief
      description of the operating principles of some types of particle formation
      processes is given. These include the rapid expansion of supercritical solutions
      (RESS), the particles from gas-saturated solution (PGSS) processes, the gas
      antisolvent process (GAS), and the supercritical antisolvent process (SAS). The
      papers have been reviewed under two groups, one involving the production of
      particles from pure biodegradable substances, and the other involving coating,
      capsule, and impregnation that contain active components, especially those that
      relate to pharmaceuticals. This review is a comprehensive review specifically
      focused on the formation of biodegradable particles for drug and gene delivery
      system using supercritical fluid and dense gas.

PMID- 18061303
TI  - Current state and future directions of pleural mesothelioma imaging.
AB  - The diagnosis, staging, and response assessment of mesothelioma pose unique
      challenges to radiologic imaging. No single, conventional imaging approach
      captures the information necessary to direct all aspects of patient management.
      Instead, the complexities of this unique disease demand the integration of
      elements cleverly adapted from different modalities. Imaging-based studies
      presented at the 8th International Conference of the International Mesothelioma
      Interest Group (IMIG) in October 2006 sought to further define the current
      practice and future potential of radiology for the mesothelioma patient. The
      imaging studies selected through a peer-review process for presentation at the
      2006 IMIG Conference were intended to frame this research in the context of the
      unique imaging challenges presented by mesothelioma while stimulating dialogue on
      the future resolution of these challenges. This communication conveys the
      pitfalls and potential of pleural mesothelioma imaging based on work presented at
      the Conference. From diagnosis to response, PET/CT to molecular bioprobes,
      volumetric analysis to computerized tumor assessment, imaging promises to provide
      valuable insight for patients with mesothelioma and the physicians who treat
      them.

PMID- 18061304
TI  - Alteration of APE1/ref-1 expression in non-small cell lung cancer: the
      implications of impaired extracellular superoxide dismutase and catalase
      antioxidant systems.
AB  - PURPOSE: Apurinic/apyrimidinic endonuclease1/ref-1(APE1/ref-1) is a key enzyme in
      the base excision repair and in transcriptional modulation against oxidative
      stress. We investigated the altered expression of APE1/ref-1 and antioxidant
      systems in lung cancer. PATIENTS AND METHODS: Tumor specimens from 48 patients
      with operable non-small cell lung cancer were obtained from 2004 to 2006.
      Immunohistochemistry, Western blot, lipid peroxidation and superoxide production
      were performed on the tumor samples and a cultured H460 cell line. RESULTS:
      APE1/ref-1 was mainly localized to the nucleus in the non-tumor regions of the
      lung cancer tissue specimens. However, nuclear and cytoplasmic expressions of
      APE1/ref-1 in the lung cancers were markedly up-regulated in the non-small cell
      lung cancer (NSCLC) specimens including squamous cell and adenocarcinoma
      specimens. Extracellular superoxide dismutase (ECSOD) and catalase were down
      regulated and manganese superoxide dismutase (MnSOD) was up-regulated in the
      tumor regions of the NSCLC. Tumor regions of the NSCLC showed higher superoxide
      production and lipid peroxidation levels than non-tumor regions. In the lung
      adenocarcinoma cell line, H460, treatment with hydrogen peroxide in the presence
      of a catalase inhibitor, aminotriazole, increased APE1/ref-1 expression,
      suggesting oxidative stress might have contributed to the induction of APE1/ref
      1. CONCLUSION: The results of this study suggest that APE1/ref-1 is up-regulated
      in the tumor regions of NSCLC. Altered expression of antioxidant systems lead to
      enhanced production of superoxide production and lipid peroxidation, which can
      induce APE1/ref-1 in the tumor regions of NSCLS.

PMID- 18061305
TI  - Detection and comparison of epidermal growth factor receptor mutations in cells
      and fluid of malignant pleural effusion in non-small cell lung cancer.
AB  - Cells or cell-free fluid of malignant pleural effusion could be important
      clinical specimen for epidermal growth factor receptor (EGFR) mutation screening
      in advanced non-small cell lung cancer (NSCLC) patients. However, their
      usefulness in mutation detection has not been well compared. In this study we
      recruited 26 East Asian NSCLC patients with malignant pleural effusion,
      determined the mutation status of EGFR in both cells and matched cell-free fluid
      with the use of sequencing and mutant-enriched PCR. After comparing the mutation
      spectrums, we found both the cells and cell-free pleural fluid may be feasible
      clinical specimen for EGFR mutation detection in unresectable NSCLC given
      sensitive genotyping assays employed. Direct sequencing could miss a significant
      portion of mutations in these heterogeneous specimens. More sensitive methods,
      such as mutant-enriched PCR and gene scan, could provide more reliable mutational
      information.

PMID- 18061306
TI  - Spontaneous osteoclastogenesis is a predictive factor for bone metastases from
      non-small cell lung cancer.
AB  - Lung cancer is a widespread disease and its incidence is growing. Since therapies
      have increased the life expectancy of lung cancer patients, the development of
      bone osteolytic metastases is becoming a common cause of morbidity. Osteolysis is
      caused by an increased osteoclast activity and may be reduced by inhibiting their
      formation and activity. We studied 60 male patients affected by NSCLC, divided in
      early and advanced stage disease. Patients' blood and urinary samples were
      collected at tumor diagnosis and at follow-up. PBMCs were cultured to investigate
      the spontaneous osteoclastogenesis. IL-7 was dosed in serum and its quantitative
      gene expression was evaluated on tumor and healthy tissues by RQ-PCR. Both at
      diagnosis and follow-up, osteolytic bone patients showed high spontaneous
      osteoclastogenesis level compared to non-bone metastatic and healthy controls.
      The presence of spontaneous osteoclastogenesis correlated with urinary crosslinks
      increase. Serum IL-7 levels were higher in bone metastatic patients than in
      patients without bone lesions and healthy controls. The serum IL-7 increase
      correlated with the osteoclastogenesis and, at least in part, depended on an
      increased IL-7 production by tumor cells. At follow-up, patients with increased
      osteoclastogenesis and serum IL-7 levels, were subjected to standard clinical
      analysis, which showed early secondary bone lesions. The in vitro assay for
      spontaneous osteoclastogenesis and serum IL-7 dosage could be useful for
      diagnostic purposes and it might be able to monitor cancer patients with a high
      risk to develop osteolytic metastases at follow-up, especially after a curative
      treatment.

PMID- 18061307
TI  - Comparison of the effects of serpin A1, a recombinant serpin A1-IGF chimera and
      serpin A1 C-terminal peptide on wound healing.
AB  - Serpin A1 (alpha1-antitrypsin, alpha1-proteinase inhibitor), a potent neutrophil
      elastase inhibitor, has therapeutic potential as a wound-healing agent. We
      compared the in vitro wound-healing action of serpin A1-IGF, a recombinant fusion
      protein of serpin A1(M351E-M358L) and insulin-like growth factor I with that
      observed in the presence of natural serpin A1 or A1-C26, the synthetic C-terminal
      26 residue peptide of serpin A1, previously shown to have mitogenic and antiviral
      activities. All agents reduced wound sizes in monolayers of the kidney epithelial
      cell line LLC-PK1 and in primary cultures of human skin fibroblasts. Wound
      reduction in primary human keratinocytes was only observed with the serpin A1-IGF
      chimera. None of the factors stimulated cell proliferation using a colorimetric
      assay, with the exception of the serpin A1-IGF chimera, which caused a
      significant increase of cell proliferation and thymidine incorporation in human
      skin fibroblasts. However, wound healing by the A1-IGF chimera was reduced in
      keratinocytes in the presence of mitomycin C, suggesting a role of cell
      proliferation in wound reduction. The hydrophobic A1-C26 peptide significantly
      increased the production of collagen I in skin fibroblasts, an appealing asset
      for skin care applications.

PMID- 18061308
TI  - Regulation of pH in the mammalian central nervous system under normal and
      pathological conditions: facts and hypotheses.
AB  - The maintenance of pH homeostasis in the CNS is of key importance for proper
      execution and regulation of neurotransmission, and deviations from this
      homeostasis are a crucial factor in the mechanism underlying a spectrum of
      pathological conditions. The first few sections of the review are devoted to the
      brain operating under normal conditions. The article commences with an overview
      of how extrinsic factors modelling the brain at work: neurotransmitters,
      depolarising stimuli (potassium and voltage changes) and cyclic nucleotides as
      major signal transducing vehicles affect pH in the CNS. Further, consequences of
      pH alterations on the major aspects of CNS function and metabolism are outlined.
      Next, the major cellular events involved in the transport, sequestration,
      metabolic production and buffering of protons that are common to all the
      mammalian cells, including the CNS cells. Since CNS function reflects tight
      interaction between astrocytes and neurons, the pH regulatory events pertinent to
      either cell type are discussed: overwhelming evidence implicates astrocytes as a
      key player in pH homeostasis in the brain. The different classes of membrane
      proteins involved in proton shuttling are listed and their mechanisms of action
      are given. These include: the Na+/H+ exchanger, different classes of bicarbonate
      transporters acting in a sodium-dependent- or -independent mode, monocarboxylic
      acid transporters and the vacuolar-type proton ATPase. A separate section is
      devoted to carbonic anhydrase, which is represented by multiple isoenzymes
      capable of pH buffering both in the cell interior and in the extracellular space.
      Next, impairment of pH regulation and compensatory responses occurring in brain
      affected by different pathologies: hypoxia/ischemia, epilepsy, hyperammonemic
      encephalopathies, cerebral tumours and HIV will be described. The review is
      limited to facts and plausible hypotheses pertaining to phenomena directly
      involved in pH regulation: changes in pH that accompany metabolic stress but have
      no distinct implications for the pH regulatory mechanisms are not dealt with. In
      most cases, the vast body of knowledge derived from in vitro studies remains to
      be verified in in vivo settings.

PMID- 18061309
TI  - Serum 24S-hydroxycholesterol and hippocampal size in middle-aged normal
      individuals.
AB  - The present study assessed the association between serum 24S-hydroxycholesterol
      (24S-OH-Chol) and 27-hydroxycholesterol (27-OH-Chol) and hippocampal volumes in
      69 middle-aged cognitively normal individuals. Results showed that subjects with
      high levels of oxysterols had significantly larger hippocampal volumes than
      subjects with low levels of oxysterols. Multiple regression analysis revealed
      that 24S-OH-Chol, but not 27-OH-Chol or cholesterol, was able to significantly
      predict hippocampal size. Future studies should elucidate whether high brain
      cholesterol metabolism in the middle age is protective against hippocampal
      atrophy and cognitive decline.

PMID- 18061310
TI  - 5-HT, prefrontal function and aging: fMRI of inhibition and acute tryptophan
      depletion.
AB  - Age-related declines in prefrontal functions and age-related declines in
      prefrontal serotonin (5-HT) are documented. The effect of 5-HT on prefrontal
      cortex (PFC) is also documented; however, no one has examined the effect of
      experimental 5-HT modulation on PFC in healthy older adults. We investigated the
      effect of 5-HT on brain functioning in 10 women over 55 (mean=63.0+/-5.3 years)
      during cognitive interference inhibition (Simon task) using fMRI and acute
      tryptophan depletion (ATD). ATD did not affect task performance; it did affect
      brain function. During sham/no depletion, participants activated brain regions
      associated with the Simon (e.g., left inferior PFC). During ATD, there was no
      prefrontal but alternative posterior brain activation. ATD relative to sham
      reduced activity in left inferior PFC, anterior cingulate and basal ganglia but
      increased activity within neocerebellum and parietal lobe. In older adults, ATD
      modulates task-relevant brain activation for cognitive interference inhibition
      and is associated with an anterior-to-posterior activation shift. Maintaining
      successful Simon performance during ATD is achieved by increasing cerebellar and
      parietal contributions to compensate for decreased fronto-cingulo-striatal
      involvement.

PMID- 18061311
TI  - Carbodithioic acid esters of fluoxetine, a novel class of dual-function
      spermicides.
AB  - Carbodithioic acid esters of fluoxetine have been prepared by replacing the
      methylamino function in aminopropane chain with carbodithioic acid ester group
      and by adding various S-2-hydroxypropyl ester of dialkyl carbodithioic acid at 3
      methylamino group. Some of these compounds showed spermicidal, antifungal and
      anti-Trichomonas activities. The study revealed that incorporation of
      carbodithioic acid residue directly into fluoxetine structure leads to compounds
      with better antifungal and anti-Trichomonas activities, and N-methyl-[3-phenyl-3
      (4-trifluoromethyl-phenoxy)-propyl]carbodithioic acid S-(2-pyrrolidino-ethyl)
      ester (14) has shown better profile than both fluoxetine and nonoxynol-9. Further
      lead optimization may yield a potent dual-function spermicide.

PMID- 18061312
TI  - Prognostic impact of disease-related malnutrition.
AB  - This review focuses on the studies investigating the prognostic implications of
      disease-related malnutrition. Malnutrition is a common problem in patients with
      chronic or severe diseases. Prevalence of hospital malnutrition ranges between
      20% and 50% depending on the criteria used in order to determine malnutrition and
      the patient's characteristics. Furthermore, nutritional status is known to worsen
      during hospital stay which is partly due to the poor recognition by the medical
      staff and adverse clinical routines. Studies have repeatedly shown that clinical
      malnutrition however has serious implications for recovery from disease, trauma
      and surgery and is generally associated with increased morbidity and mortality
      both in acute and chronic diseases. Length of hospital stay is significantly
      longer in malnourished patients and higher treatment costs are reported in
      malnutrition. Since it has been demonstrated that proper nutritional care can
      reduce the prevalence of hospital malnutrition and costs, nutritional assessment
      is mandatory in order to recognise malnutrition early and initiate timely
      nutritional therapy.

PMID- 18061313
TI  - BMI nomogram [corrected].
AB  - I have devised a nomogram [corrected] that allows easy determination of a
      person's body mass index (BMI), i.e., by simply drawing a single line on the
      graph to connect the height and weight. Conversely, the body weight corresponding
      to an arbitrary BMI may be determined similarly. This nomogram [corrected] is a
      useful and convenient tool in that it can be printed on a sheet of paper.

PMID- 18061314
TI  - Fear of injections is a reason for not to vaccinate their children, say
      caretakers.

PMID- 18061315
TI  - Towards an oral influenza vaccine: comparison between intragastric and
      intracolonic delivery of influenza subunit vaccine in a murine model.
AB  - In this paper we investigated to which part of the gastro-intestinal (GI) tract,
      the upper or lower part, an oral influenza vaccine should be targeted to result
      in an effective immune response in mice. Our study demonstrates that without
      adjuvant substantial systemic but low respiratory mucosal immune responses were
      induced in mice after delivery of influenza subunit vaccine to the upper GI-tract
      (intragastric) as well as the lower GI-tract (intracolonically). When the vaccine
      was adjuvanted with Escherichia coli heat-labile enterotoxin (LT) these responses
      were significantly enhanced. Interestingly, intracolonic administration of
      vaccine with adjuvant also resulted in enhanced cellular immune responses and the
      desired Th1-skewing of these responses. Intragastric administration of the
      adjuvanted vaccine also increased T-helper responses. However, Th1-skewing was
      absent. In conclusion, the right combination of strong mucosal adjuvant (e.g. LT)
      and antigen delivery site (e.g. the lower part of the gastro-intestinal tract)
      might result in effective vaccination via the oral route.

PMID- 18061316
TI  - Mucosal priming with replicative Tiantan vaccinia and systemic boosting with DNA
      vaccine raised strong mucosal and systemic HIV-specific immune responses.
AB  - An effective vaccine strategy for HIV-1 will probably require the induction and
      maintenance of both humoral and cellular immunity at mucosal and systemic sites.
      We tested a new prime-boost approach of intranasal priming with 3 x 10(6) PFU of
      replicative recombinant Tiantan vaccinia virus (rTTV) and intramuscular boosting
      with 100 microg DNA plasmid expressing HIV-1 Gag in BALB/c mice along with other
      strategies. Our data demonstrated that intranasal priming with replicative
      recombinant Tiantan vaccinia and intramuscular boosting with DNA vaccine raised
      the highest vaginal IgA and systemic T-cell responses, and modest lung IgA and
      sera IgG responses among all vaccination regimens; each vaccination regimen
      generated its own imprint of the most preferential T-cell receptor usage of
      Vbeta. These results demonstrate that the combination of intranasal priming with
      replicative recombinant Tiantan vaccinia and intramuscular boosting with DNA
      vaccine is a preferable regimen for induction of both T-cell and humoral immune
      responses at mucosal and systemic sites.

PMID- 18061317
TI  - Characterization of immunity induced by M2e of influenza virus.
AB  - The extracellular-domain of influenza Matrix 2 protein (M2e) is considered as a
      putative target for designing universal influenza vaccines. However, the
      mechanism by which M2-based vaccine induces protection has not been clear. In
      this study, we analyzed the immunity induced by free synthetic M2e peptide and
      found the peptide was highly immunogenic. Without carrier proteins, the synthetic
      M2e peptide could induce M2e-specific IgG antibodies in both incomplete Freund's
      and aluminum adjuvant. The peptide could also provoke M2e-specific T cell
      response, which could not be mounted by influenza virus. Moreover, immunization
      with M2e peptide could protect mice from a lethal challenge with influenza virus.
      These results provide useful information for the development of M2e-based
      influenza vaccine.

PMID- 18061318
TI  - Prevalence of hepatitis A virus risk factors in a very low endemic country,
      Switzerland.
AB  - We aimed to estimate the population-based lifetime exposure to guidelines-based
      hepatitis A virus (HAV) risk factors in a country model with very low HAV
      endemicity. A cross-sectional survey among randomly selected residents of
      Switzerland aged 20-60 years was performed assessing the HAV exposure risk
      according to the U.S. and the Swiss guidelines. The adjusted prevalence of
      lifetime exposure to HAV-associated risk exceeded 80% with travel being the most
      important risk factor. In addition, not only the HAV vaccination coverage was low
      but also lack of awareness was widespread. As projections indicate a further
      increase in travel volume resulting imported HAV infections with subsequent
      transmission among the resident population are a public health concern and a
      universal HAV vaccination strategy for HAV should be evaluated.

PMID- 18061319
TI  - Partitioning of radiostrontium in marine aqueous suspensions: laboratory
      experiments and modeling studies.
AB  - Quantitative information on the adsorption/desorption of radionuclides by
      suspended loads is important in the study of their environmental behavior. In
      this paper, controlled laboratory experiments were directed at studying the
      kinetic transfer and final distribution of radiostrontium in aqueous suspensions
      using 85Sr as tracer. The results showed that the uptake of 85Sr in seawater can
      be properly described by one reversible-reaction model. However, in the absence
      of competitive cations, it has been shown that two reactions of different
      characteristic times are unambiguously involved in the kinetic evolution of
      adsorption. Thus, a modeling approach consisting of three-box model has been
      applied. The model predicts in a satisfactory way the time evolution of
      activities in the dissolved phase and two sites in the particles. Experimental
      evidence showed, through comparison among kinetic and distribution coefficients
      corresponding to different conditions, that Ca2+ affects strongly the rate and
      extent of Sr uptake by suspended particles. On the other hand, distribution
      coefficients were found to be sensitive to changes in suspended particulate
      matter (SPM) concentration, exhibiting a reverse effect with this parameter on
      the adsorption. In addition, desorption from particles is important showing that
      Sr can be easily released due to cation-exchange processes.

PMID- 18061320
TI  - An overview of BORIS: Bioavailability of Radionuclides in Soils.
AB  - The ability to predict the consequences of an accidental release of radionuclides
      relies mainly on the level of understanding of the mechanisms involved in
      radionuclide interactions with different components of agricultural and natural
      ecosystems and their formalisation into predictive models. Numerous studies and
      databases on contaminated agricultural and natural areas have been obtained, but
      their use to enhance our prediction ability has been largely limited by their
      unresolved variability. Such variability seems to stem from incomplete knowledge
      about radionuclide interactions with the soil matrix, soil moisture, and
      biological elements in the soil and additional pollutants, which may be found in
      such soils. In the 5th European Framework Programme entitled Bioavailability of
      Radionuclides in Soils (BORIS), we investigated the role of the abiotic (soil
      components and soil structure) and biological elements (organic compounds,
      plants, mycorrhiza, and microbes) in radionuclide sorption/desorption in soils
      and radionuclide uptake/release by plants. Because of the importance of their
      radioisotopes, the bioavailability of three elements, caesium, strontium, and
      technetium has been followed. The role of one additional non-radioactive
      pollutant (copper) has been scrutinised in some cases. Role of microorganisms
      (e.g., K(d) for caesium and strontium in organic soils is much greater in the
      presence of microorganisms than in their absence), plant physiology (e.g.,
      changes in plant physiology affect radionuclide uptake by plants), and the
      presence of mycorrhizal fungi (e.g., interferes with the uptake of radionuclides
      by plants) have been demonstrated. Knowledge acquired from these experiments has
      been incorporated into two mechanistic models CHEMFAST and BIORUR, specifically
      modelling radionuclide sorption/desorption from soil matrices and radionuclide
      uptake by/release from plants. These mechanistic models have been incorporated
      into an assessment model to enhance its prediction ability by introducing the
      concept of bioavailability factor for radionuclides.

PMID- 18061321
TI  - Arbuscular mycorrhizas contribute to phytostabilization of uranium in uranium
      mining tailings.
AB  - Uranium (U) tailings pose environmental risks and call for proper remediation. In
      this paper medic and ryegrass plants were used as host plants to examine whether
      inoculation with an AM fungus, Glomus intraradices, would help phytostabilization
      of U tailings. The need of amending with uncontaminated soil for supporting plant
      survival was also examined by mixing soil with U tailing at different mixing
      ratios. Soil amendment increased plant growth and P uptake. Ryegrass produced a
      more extensive root system and a greater biomass than medic plants at all mixing
      ratios. Medic roots were extensively colonized by G. intraradices whereas
      ryegrass were more sparsely colonized. Plant growth was not improved by
      mycorrhizas, which, however, improved P nutrition of medic plants. Medic plants
      contained higher U concentrations and showed higher specific U uptake efficiency
      compared to ryegrass. In the presence of U tailing, most U had been retained in
      plant roots, and this distribution pattern was further enhanced by mycorrhizal
      colonization. The results suggest a role for AM fungi in phytostabilization of U
      tailings.

PMID- 18061322
TI  - Intralimb coordination variability in peripheral arterial disease.
AB  - BACKGROUND: Increased variability has been traditionally associated with
      decreased movement performance due to disease and aging. However, recent research
      indicates that variability may be of functional importance in motor control. Thus
      the purpose of this study was to determine whether individuals with peripheral
      arterial disease and suffering from intermittent claudication have reduced
      intralimb joint coordination variability compared to individuals without
      peripheral arterial disease. A further aim was to examine the efficacy of various
      techniques used to describe intralimb joint coordination variability. METHODS:
      Participants with peripheral arterial disease and suffering from intermittent
      claudication (n=28) were selected based on an appropriate history of peripheral
      arterial disease and intermittent claudication, ankle brachial pressure index
      <0.9 in at least 1 leg and a positive Edinburgh claudication questionnaire
      response. A further group of participants (n=25) free of peripheral arterial
      disease (ankle brachial pressure index >0.9) and who were non-regular exercisers
      were recruited from the community to act as age and mass matched controls. All
      participants underwent 2D angular kinematics analysis during normal walking.
      Intralimb coordination variability was measured using parameterization, vector
      coding and normalized root mean square techniques applied to relative motion
      plots of various joint couplings. Differences between groups were examined by one
      way ANOVA. FINDINGS: Participants with peripheral arterial disease and suffering
      from intermittent claudication displayed significantly greater intralimb joint
      coordination variability than age and mass matched controls participants for all
      joint couplings using all intralimb joint coordination variability techniques.
      INTERPRETATION: These findings suggest that higher levels of intralimb joint
      coordination variability of the lower limbs in participants with peripheral
      arterial disease and suffering from intermittent claudication may be an
      adaptation of the motor control system to deal with perturbations associated with
      the gradual onset of claudication pain.

PMID- 18061323
TI  - Sulphur transformation and deposition in the rhizosphere of Juncus effusus in a
      laboratory-scale constructed wetland.
AB  - Sulphur cycling and its correlation to removal processes under dynamic redox
      conditions in the rhizosphere of helophytes in treatment wetlands are poorly
      understood. Therefore, long-term experiments were performed in laboratory-scale
      constructed wetlands treating artificial domestic wastewater in order to
      investigate the dynamics of sulphur compounds, the responses of plants and
      nitrifying microorganisms under carbon surplus conditions, and the generation of
      methane. For carbon surplus conditions (carbon:sulphate of 2.8:1) sulphate
      reduction happened but was repressed, in contrast to unplanted filters mentioned
      in literature. Doubling the carbon load caused stable and efficient sulphate
      reduction, rising of pH, increasing enrichment of S(2-) and S(0) in pore water,
      and finally plant death and inhibition of nitrification by sulphide toxicity. The
      data show a clear correlation of the occurrence of reduced S-species with
      decreasing C and N removal performance and plant viability in the experimental
      constructed wetlands.

PMID- 18061324
TI  - Review of cognitive, cognitive-behavioral, and neural-based interventions for
      Attention-Deficit/Hyperactivity Disorder (ADHD).
AB  - Primary evidence-based treatment approaches for ADHD involve pharmacological and
      behavioral treatments. However, there continue to be investigations of cognitive
      behavioral, cognitive, and neural-based intervention approaches that are not
      considered evidence-based practice. These particular treatments are summarized,
      as they all involve training in cognitive skills or cognitive strategies. We
      identified 26 studies (six cognitive-behavioral, six cognitive, and 14 neural
      based), and calculated effect sizes where appropriate. Overall, our analysis
      suggests that further research is needed to determine the efficacy of these
      approaches on both cognitive and behavioral outcome measures, but that some of
      these methods show promise for treating ADHD. We discuss some important
      conceptual and methodological issues that need to be taken into account for
      future research in order to evaluate the clinical efficacy of these approaches.

PMID- 18061325
TI  - Paying the price: the cost and consequences of emergency obstetric care in
      Burkina Faso.
AB  - Substantial healthcare expenses can impoverish households or push them further
      into poverty. In this paper, we examine the cost of obstetric care and the social
      and economic consequences associated with exposure to economic shocks up to a
      year following the end of pregnancy in Burkina Faso. Burkina Faso is a low-income
      country with poor health outcomes and a poorly functioning health system. We
      present an inter-disciplinary analysis of an ethnographic study of 82 women
      nested in a prospective cohort study of 1013 women. We compare the experiences of
      women who survived life-threatening obstetric complications ('near-miss' events)
      with women who delivered without complications in hospitals. The cost of
      emergency obstetric care was significantly higher than the cost of care for
      uncomplicated delivery. Compared with women who had uncomplicated deliveries,
      women who survived near-miss events experienced substantial difficulties meeting
      the costs of care, reflecting the high cost of emergency obstetric care and the
      low socioeconomic status of their households. They reported more frequent sale of
      assets, borrowing and slower repayment of debt in the year following the
      expenditure. Healthcare costs consumed a large part of households' resources and
      women who survived near-miss events continued to spend significantly more on
      healthcare in the year following the event, while at the same time experiencing
      continued cost barriers to accessing healthcare. In-depth interviews confirm that
      the economic burden of emergency obstetric care contributed to severe and long
      lasting consequences for women and their households. The necessity of meeting
      unexpectedly high costs challenged social expectations and patterns of
      reciprocity between husbands, wives and wider social networks, placed enormous
      strain on everyday survival and shaped physical, social and economic well-being
      in the year that followed the event. In conclusion, we consider the implications
      of our findings for financing mechanisms for maternity care in low-income
      settings.

PMID- 18061327
TI  - Comments on "Addition of lamotrigine to valproic acid: a successful outcome in a
      case of rapid-cycling bipolar affective disorder".

PMID- 18061326
TI  - Investigating the neuropsychological and neuroanatomical changes that occur over
      the first 2-3 years of illness in patients with first-episode schizophrenia.
AB  - OBJECTIVE: This study explored the concurrent courses of the neuroanatomical and
      neuropsychological changes that occurred over the first 2-3 years of illness in
      patients with first-episode schizophrenia (FES). METHODS: Fifty-two patients with
      FES underwent neuropsychological testing and a structural magnetic resonance
      imaging (sMRI) scan within three months of their first presentation to mental
      health services with psychotic symptoms (time1). Patients' cognitive performance
      was evaluated via an extensive neuropsychological test battery, which assessed 9
      cognitive domains. Of the 52 patients at time1, 32 returned 2-3 years later
      (time2) for follow-up neuropsychological testing, and 20 of these also underwent
      follow-up sMRI. MR images were preprocessed in SPM99. Grey matter volumes of
      patients' whole-brain, frontal lobes and temporal lobes were calculated by
      convolving the preprocessed images with manually-drawn binary masks. RESULTS:
      Patients exhibited longitudinal improvements in full-scale IQ, performance IQ and
      visual memory. In contrast, concurrent reductions in grey matter were observed
      for the whole-brain (3% reduction) and the frontal lobe (3.65% reduction).
      Furthermore, the extent of patients' whole-brain and frontal-lobe grey matter
      changes were positively correlated with longitudinal changes in verbal learning
      and memory. DISCUSSION: The results of this study suggest that while the early
      stages of schizophrenia are associated with a mild improvement in patients'
      overall cognitive functioning, they are also associated with progressive grey
      matter atrophy.

PMID- 18061328
TI  - The metabolisms of agaritine, a mushroom hydrazine in mice.
AB  - The mushroom hydrazine agaritine was measured in mouse plasma and urine using
      LC/MS/MS, which is highly specific. Agaritine concentration peaked 20 min after
      oral administration to mice (4.0 and 40 mg/kg). The concentration gradually
      decreased and returned to the basal level in 100 min. The maximum concentration,
      the time to the maximum concentration, and the half life were 0.37 microg/ml
      plasma, 0.33 h, and 0.71 h, respectively after administration of agaritine at 40
      mg/kg body weight. One agaritine metabolite was found in the plasma and the urine
      from agaritine-administered mice. The structure of metabolites of agaritine by
      gamma-GT was next investigated using LC/MS. HMPH proved to be generated from
      agaritine. The oxidative stress marker 8-OHdG was detected in agaritine
      administered mouse urine. After administration, the 8-OHdG level immediately
      tripled, and then decreased to the control level over 48 h. Its level then
      elevated again and remained high for 11 days. These results suggest that
      agaritine quickly metabolizes and disappears in the plasma, whereas DNA damage
      lasts for a long time after a single administration of agaritine to mice.

PMID- 18061329
TI  - Detoxification of patulin and ochratoxin A, two abundant mycotoxins, by lactic
      acid bacteria.
AB  - Aim of the present study was to investigate the detoxification of two abundant
      mycotoxins, namely ochratoxin A (OTA) and patulin (PAT) which are frequently
      found in human foods, by lactic acid bacteria. The removal of the two mycotoxins
      from liquid medium by thirty different LAB strains was analyzed in a screening
      trial by the use of HPLC coupled with UV- or fluorescence detection. Two highly
      effective strains were identified; Lactobacillus acidophilus VM 20 caused a
      decrease of OTA by > or = 95% and Bifidobacterium animalis VM 12 reduced PAT
      levels by 80%. Subsequently experiments showed that the binding of these
      compounds depends on different parameters, i.e. the concentration of toxins, the
      cell density, the pH-value and on the viability of the bacteria. To proof that
      the decrease of the toxins by LAB from liquid medium results in a reduction of
      their toxic properties, micronucleus (MCN) assays were conducted with a human
      derived hepatoma cell line (HepG2). Indeed, a substantial decrease (39-59%) of
      OTA and PAT induced MCN formation was observed with the most effective strains
      detected in the chemical analyses. Furthermore, also the inhibition of the cell
      division rates by the toxins was significantly reduced. These findings indicate
      that certain LAB strains are able to detoxify the two toxins and may be useful to
      protect humans and/or animals against the adverse health effects of these
      compounds.

PMID- 18061330
TI  - Re: The effect of aspartame metabolites on the suckling rat frontal cortex
      acetylcholinesterase. An in vitro study.

PMID- 18061331
TI  - D-Serine exposure resulted in gene expression changes indicative of activation of
      fibrogenic pathways and down-regulation of energy metabolism and oxidative stress
      response.
AB  - Renal toxicity can commonly occur after exposure to xenobiotics, pharmaceutical
      agents or environmental pollutants. Changes in the gene expression in kidney
      parenchymal cells that precede and/or accompany renal injury may be hallmark
      critical events in the onset of pathologic changes of renal functions. Over the
      last several years, transcriptomic analysis has evolved to enable simultaneous
      analysis of the expression profiles of tens of thousands of genes in response to
      various endogenous and exogenous stimuli. In this study, we investigated gene
      expression changes in the kidney after acute exposure to a nephrotoxin, D-serine,
      which targets the proximal tubule of the kidney. Male F-344 rats injected
      intraperitoneally with a single dose of D-serine (5, 20, 50, 200 or 500 mg/kg),
      and gene expression profiles in the kidney were determined using the Affymetrix
      RAE230A gene arrays at 96 h post-dosing. D-serine treatment resulted in the up-
      and down-regulation of 1158 and 749 genes, respectively, over the entire dose
      range based on the intersection of the results of t-test, p<0.01 over two
      consecutive doses, and ANOVA with Bonferonni correction for multiple testing.
      Interestingly, both the up-and down-regulated genes show a unified dose response
      pattern as revealed in the self-organized map clustering analysis using the
      expression profiles of the 1907 differentially expressed genes as input data.
      There appears to be minimal changes in the expression level of these genes in the
      dose range of 5-50 mg/kg, while the most prominent changes were observed at the
      highest doses tested, i.e. 200 and 500 mg/kg. Pathway analysis of the
      differentially expressed genes showed perturbation of a large number of
      biological processes/pathways after d-serine exposure. Among the up-regulated
      pathways are actin cytoskeleton biogenesis and organization, apoptosis, cell
      cycle regulation, chromatin assembly, excision repair of damaged DNA, DNA
      replication and packaging, protein biosynthesis, metabolism and transport,
      inflammatory response, proteasome-mediated degradation of oxidatively damaged
      cytosolic proteins, Ras protein signal transduction, TGF-beta signaling pathway
      and mRNA transcription, processing, splicing and transport. On the other hand,
      major metabolic pathways, which include carbohydrate metabolism, TCA cycle,
      oxidative phosphorylation, ATP synthesis coupled electron transport, amino acid
      metabolism and transport, lipid metabolism, nucleotide metabolism, and vitamin
      metabolism, and oxidative stress response including induction of antioxidant
      genes and glutathione metabolism are down-regulated. As tubular epithelia have
      strong energy demand for normal functions, down-regulation of energy metabolism
      after D-serine treatment may be related to the mechanism of its nephrotoxicity.
      In addition, hydrogen peroxide, a reactive oxygen species, is produced as a
      byproduct of the metabolism of D-serine by D-amino acid oxidase in the
      peroxisomes of the tubular epithelia. Down-regulation of pathways for antioxidant
      genes induction and glutathione metabolism will likely exacerbate the
      cytotoxicity of this reactive oxygen species. The observation that the genes
      involved in apoptosis, DNA repair, proteasome pathway for the degradation of
      oxidatively damaged cytosolic proteins were up-regulated lends some supports to
      this premise. Up-regulation of pathways of cell proliferation cycle, DNA
      replication and gene expression process, including mRNA transcription,
      processing, splicing, transport, translation initiation, and protein transport
      along with protein complex assembly, suggests ongoing tissue repair and
      regeneration. Consistent with the fibrogenic function of the TGF-beta signaling
      pathway in various experimental renal diseases, genes encoding major
      extracellular matrix components such as collagens, laminins, fibronectin 1 and
      tenascins are also strongly up-regulated. Taken together, the results of this
      study provide important insights into the molecular mechanism of D-serine
      nephrotoxicity, as well as the activation of specific cellular pathways in
      response to this toxic insult.

PMID- 18061332
TI  - Oxidative stress and DNA damage induced by cadmium in the human keratinocyte
      HaCaT cell line: role of glutathione in the resistance to cadmium.
AB  - Cadmium affects the cellular homeostasis and generates damage via complex
      mechanisms involving interactions with other metals and oxidative stress
      induction. In this work we used a human keratinocyte cell line (HaCaT) as a model
      to study the oxidative damage induced by cadmium to cellular macromolecules, its
      effect on the antioxidant systems and the role of glutathione in cell protection
      toward cadmium toxicity. The cells were incubated for 24 and 48 h with cadmium
      (3, 15, 50 and 100 microM). High doses of cadmium were required to induce a
      cytotoxicity: 100 microM lead to 30% mortality after 24h and 50% after 48 h. The
      oxidation of lipids and proteins and the DNA damage, respectively, assessed by
      thiobarbituric acid reactants determination, thiol group measurement and comet
      assay, were observed for 50-100 microM cadmium. The cytotoxic effects were
      strongly correlated to the cellular cadmium content. The glutathione peroxidase
      and the catalase activities were decreased, while the glutathione reductase
      activity and the glutathione concentration were increased after cadmium
      treatment. The superoxide dismutases activities were unchanged. A depletion in
      glutathione prior to cadmium exposure increased the cytotoxic effects and
      provoked DNA damage. Our results suggested that the hydroxyl radical could be the
      major compound involved in the oxidative stress generated by cadmium and that
      glutathione could play a major role in the protection of HaCaT cells from
      cytotoxicity but mostly from DNA damage induced by cadmium.

PMID- 18061333
TI  - An investigation into most effective method of treating stained teeth: an in
      vitro study.
AB  - OBJECTIVE: To assess the most efficacious method of treating stained teeth:
      bleaching alone, veneering alone or a combination of bleaching and veneering and
      whether the choice alters depending on the degree of staining. METHODS: Extracted
      teeth were sectioned to give 117 samples. These samples were split into
      unstained, lightly and darkly stained groups based on CIE-Lab value L*. The
      lightly and darkly stained groups were stained using tea. Teeth from each group
      were then assigned to one of four subgroups (control (C), bleaching alone (B),
      veneering alone (V), or a combination of bleaching and veneering (BV), each
      containing 13 samples. Veneering was performed using 0.8-mm thick ceramic veneer
      of shade B1. CIE-Lab values were recorded using a spectrophotometer and the
      colour difference (Delta E) was calculated for each intervention. The final
      colour was compared to the value for obtained from a B1 (Vita) Shade tab.
      Statistical significance was assessed using analysis of variance. RESULTS: In all
      three test groups, intervention resulted in a statistically significant colour
      change compared to the C group (p<or=0.001). In the unstained group, the only
      intervention that reached statistically significant parity to B1 was BV
      (p=0.015). In the lightly stained group, BV produced the most colour change and
      the value closest to B1 (p<or=0.003). In dark group, BV produced the greatest
      colour change and the value closest to B1 however; this was not statistically
      significantly better than V (p=0.146). CONCLUSIONS: All the interventions
      produced a statistically significant and clinically visible colour change
      compared to the control. External light-activated bleaching produced a clinically
      visible colour change. In all groups the combination of bleaching and veneering
      gave the closest value to B1.

PMID- 18061334
TI  - Rapid-equilibrium rate equations for the enzymatic catalysis of A+B=P+Q over a
      range of pH.
AB  - This article shows how pKs for the enzymatic site and enzyme-substrate complexes
      can be obtained from kinetic experiments on the reaction A+B=P+Q, with and
      without the consumption of hydrogen ions. The rapid-equilibrium rate equation
      makes it possible to obtain the pKs and chemical equilibrium constants involved
      in the mechanism, the apparent equilibrium constant K' for the catalyzed
      reaction, and the number of hydrogen ions consumed in the rate-determining
      reaction. Experimentally-determined Michaelis constants can be adjusted for the
      pKs of the substrates A, B, P, and Q so that it is easier to obtain the pKs of E,
      EA, EB, EAB, EQ, and EPQ, and the chemical equilibrium constants. Reaction rates
      are discussed for the forward reaction ordered A+B=ordered P+Q with zero, one, or
      two hydrogen ions consumed in the rate-determining reaction and for random
      A+B=ordered P+Q with zero, one, or two hydrogen ions consumed in the rate
      determining reaction. When hydrogen ions are consumed in the rate-determining
      reaction, there is a new factor 10(n)(pH) in the rate equation, where n is the
      number of hydrogen ions consumed in the rate-determining reaction for the forward
      reaction. The integer n can be obtained from rate measurements over a range of
      pH, but it cannot be determined from thermodynamic measurements.

PMID- 18061335
TI  - Advances in specific immunotherapy for prostate cancer.
AB  - OBJECTIVES: The absence of effective therapies for advanced prostate cancer has
      entailed an intensive search for novel treatments. This review presents an
      overview of specific immunotherapeutic strategies for prostate cancer. METHODS:
      Current literature was reviewed regarding the identification of tumor antigens
      and the design of T-cell- and antibody-based immunotherapy for prostate cancer.
      The PubMed database was searched using the key words antibodies, clinical trials,
      dendritic cells, immunotherapy, prostate cancer, and T cells. RESULTS: T cells
      and antibodies are powerful components of the specific antitumor immune response.
      CD8+ cytotoxic T lymphocytes (CTLs) efficiently destroy tumor cells. CD4+ T cells
      improve the antigen-presenting capacity of dendritic cells (DCs) and support the
      stimulation of tumor-reactive CTLs. Monoclonal antibodies exhibit their antitumor
      effects via antibody-dependent cellular cytotoxicity and complement activation.
      Consequently, much attention has been given to the identification of tumor
      antigens that represent attractive targets for specific immunotherapy. Several
      prostate cancer-related antigens were described and used in clinical trials. Such
      studies were based on the administration of peptides, proteins, or DNA.
      Furthermore, men with prostate cancer were vaccinated with peptide-, protein-, or
      RNA-loaded DCs, which display an extraordinary capacity to induce tumor-reactive
      T cells. Monoclonal antibodies directed against surface antigens were also used.
      Clinical trials revealed that immunotherapeutic strategies represent safe and
      feasible concepts for the induction of immunologic and clinical responses in men
      with prostate cancer. CONCLUSIONS: Specific immunotherapy represents a promising
      treatment modality for prostate cancer. Further improvement of the current
      approaches is required and may be achieved by combining T-cell- and antibody
      based vaccination strategies with radio-, hormone-, chemo-, or antiangiogenic
      therapy.

PMID- 18061336
TI  - Editorial comment on: diagnostic accuracy of computed tomography-guided
      percutaneous biopsy of renal masses.

PMID- 18061337
TI  - ADAM9 expression is a significant and independent prognostic marker of PSA
      relapse in prostate cancer.
AB  - OBJECTIVES: A disintegrin and metalloprotease (ADAM) 9 has been implicated in
      tumour progression of prostate cancer. We evaluated the expression of ADAM9 on
      protein and messenger RNA (mRNA) level in a larger cohort of prostate cancer
      cases following prostatectomy and correlated the findings with
      clinicopathological parameters including prostate-specific antigen (PSA) relapse
      times. METHODS: We immunostained 198 clinicopathologically characterised prostate
      cancer cases for ADAM9. For 25 additional cases, ADAM9 mRNA of microdissected
      tumour and normal tissue was analysed via quantitative reverse transcriptase
      polymerase chain reaction. RESULTS: ADAM9 was significantly upregulated in
      prostate cancer compared with normal tissue on mRNA and protein level. ADAM9
      protein expression was significantly associated with shortened PSA relapse-free
      survival in univariate and multivariate analyses, particularly in patients who
      had received prior androgen ablation. CONCLUSIONS: ADAM9 is overexpressed in
      prostate cancer cases and is an independent prognostic marker of PSA relapse-free
      survival following radical prostatectomy. Further studies are needed to verify
      its role as a predictive marker of response to androgen ablation.

PMID- 18061338
TI  - Editorial comment on: ADAM9 expression is a significant and independent
      prognostic marker of PSA relapse in prostate cancer.

PMID- 18061339
TI  - Diagnostic accuracy of computed tomography-guided percutaneous biopsy of renal
      masses.
AB  - OBJECTIVE: Modern imaging modalities increase the detection of small (<or=4 cm)
      renal tumors, of which about 20% are benign. As a result, minimal invasive
      treatments, such as radiofrequency ablation and cryotherapy, and surveillance
      strategies are gaining popularity. Information that would be helpful when
      choosing the most appropriate management strategy for this patient group could be
      obtained from pretherapeutic image-guided biopsy. METHODS: Under computed
      tomography (CT)-fluoroscopic guidance 78 patients with solid renal tumors
      prospectively underwent 18-gauge core biopsy. In addition, using the same sheath,
      fine-needle aspiration was taken in 44 patients and analyzed cytologically. The
      renal masses were subsequently removed surgically and evaluated histologically.
      RESULTS: Mean patient age was 63+/-13.5 yr; mean tumor size was 4+/-1.8 cm. The
      sensitivity of core biopsy and fine-needle aspiration for the detection of renal
      cell carcinoma (RCC) was 93.5% and 90.6%, respectively; Fuhrman grade was
      correctly predicted in 76% and 28% and the correct histologic subtype was
      identified 91% and 86%, respectively. Cytology from fine-needle aspiration
      revealed a sensitivity in detecting malignant and benign lesions of 100% and 75%,
      respectively. Two of the renal tumors diagnosed as oncocytomas on core biopsy
      were hybrid tumors with scattered areas of oncocytomas and chromophobe RCC.
      Complications of CT-guided biopsy included one marginal pneumothorax, which
      resolved under conservative management, and four small perirenal hematomas
      detected at follow-up ultrasonography not requiring further therapy. CONCLUSION:
      CT-guided percutaneous preoperative renal tumor biopsy had a high diagnostic
      accuracy, particularly in predicting malignancy.

PMID- 18061340
TI  - Editorial comment on: ADAM9 expression is a significant and independent
      prognostic marker of PSA relapse in prostate cancer.

PMID- 18061341
TI  - Alzheimer's disease-related changes in diseases characterized by elevation of
      intracranial or intraocular pressure.
AB  - In this review, we focus on the coexistence of Alzheimer's disease-related
      changes in brain diseases, such as normal pressure hydrocephalus and traumatic
      brain injury, and in glaucoma at the level of the retinal ganglion cells. This is
      a group of diseases that affect central nervous system tissue and are
      characterized by elevation of intracranial or intraocular pressure and/or local
      shear stress and strain. In considering possible mechanisms underlying Alzheimer
      type changes in these diseases, we briefly summarize recent evidence indicating
      that caspase activation and abnormal processing of beta-amyloid precursor
      protein, which are important events in Alzheimer's disease, may play a role both
      in glaucoma and following traumatic brain injury. With regard to normal pressure
      hydrocephalus, evidence suggests that changes in cerebrospinal fluid circulatory
      dynamics ultimately may result in reduced clearance of neurotoxins, such as beta
      amyloid peptides and tau protein, that play a role in the pathogenesis of
      Alzheimer's disease. Data presented in this review could be interpreted to
      suggest that Alzheimer-type changes in these diseases may result at least in part
      from exposure of central nervous system tissue to increased levels of mechanical
      stress. Evidence for such a relationship is of major importance because it may
      support an association between elevated mechanical load and the development of
      Alzheimer-type lesions. Further studies are warranted, however, especially to
      elucidate the role of elevated mechanical forces in Alzheimer's disease
      neuropathogenesis.

PMID- 18061342
TI  - Catalytic activity of CuOn-La2O3/gamma-Al2O3 for microwave assisted ClO2
      catalytic oxidation of phenol wastewater.
AB  - In order to develop a catalyst with high activity and stability for microwave
      assisted ClO2 catalytic oxidation, we prepared CuOn-La2O3/gamma-Al2O3 by
      impregnation-deposition method, and determined its properties using BET, XRF, XPS
      and chemical analysis techniques. The test results show that, better thermal
      ability of gamma-Al2O3 and high loading of Cu in the catalyst can be achieved by
      adding La2O3. The microwave assisted ClO2 catalytic oxidation process with CuOn
      La2O3/gamma-Al2O3 used as catalyst was also investigated, and the results show
      that the catalyst has an excellent catalytic activity in treating synthetic
      wastewater containing 100 mg/L phenol, and 91.66% of phenol and 50.35% of total
      organic carbon (TOC) can be removed under the optimum process conditions.
      Compared with no catalyst process, CuOn-La2O3/gamma-Al2O3 can effectively degrade
      contaminants in short reaction time and with low oxidant dosage, extensive pH
      range. The comparison of phenol removal efficiency in the different process
      indicates that microwave irradiation and catalyst work together to oxidize phenol
      effectively. It can therefore be concluded from results and discussion that CuOn
      La2O3/gamma-Al2O3 is a suitable catalyst in microwave assisted ClO2 catalytic
      oxidation process.

PMID- 18061343
TI  - Identifying anthropogenic and natural influences on extreme pollution of
      respirable suspended particulates in Beijing using backward trajectory analysis.
AB  - In China, daily respirable suspended particulate (RSP, particles with aerodynamic
      diameters less than 10 microm) concentrations exceeding 420 microg m(-3) are
      considered "hazardous" to health. These can lead to the premature onset of
      certain diseases and premature death of sick and elderly people; even healthy
      people are warned to avoid outdoor activity when RSP concentrations are high.
      Such high pollution levels are defined as extreme RSP pollution events. Recent
      epidemiological studies have shown that a distinct difference exists between the
      health effects caused by natural sources and anthropogenic sources, mandating
      knowledge of the source of extreme RSP pollution. Twenty-six extreme RSP
      pollution events were recorded in Beijing from January 2003 to December 2006. The
      HYSPLIT4 (Hybrid Single Particle Lagrangian Integrated Trajectory) model (Version
      4) was used to discriminate the sources of these extreme RSP pollution events.
      The model found that twelve events were caused from natural sources (dust
      storms), nine events from anthropogenic sources (e.g., vehicles and industrial
      activities, etc.) under quasi-quiescent weather, and five events were from mixed
      causes. Identifying such events will be valuable in epidemiological studies on
      air pollution in Beijing.

PMID- 18061344
TI  - Advances in science and technology of modern energetic materials: an overview.
AB  - Energetic materials such as explosives, propellants and pyrotechnics are widely
      used for both civilian and military explosives applications. The present review
      focuses briefly on the synthesis aspects and some of the physico-chemical
      properties of energetic materials of the class: (a) aminopyridine-N-oxides, (b)
      energetic azides, (c) high nitrogen content energetic materials, (d) imidazoles,
      (e) insensitive energetic materials, (f) oxidizers, (g) nitramines, (h) nitrate
      esters and (i) thermally stable explosives. A brief comment is also made on the
      emerging nitration concepts. This paper also reviews work done on primary
      explosives of current and futuristic interest based on energetic co-ordination
      compounds. Lead-free co-ordination compounds are the candidates of tomorrow's
      choice in view of their additional advantage of being eco-friendly. Another
      desirable attribute of lead free class of energetic compounds is the presence of
      almost equivalent quantity of fuel and oxidizer moieties. These compounds may
      find wide spectrum of futuristic applications in the area of energetic materials.
      The over all aim of the high energy materials research community is to develop
      the more powerful energetic materials/explosive formulations/propellant
      formulations in comparison to currently known benchmark materials/compositions.
      Therefore, an attempt is also made to highlight the important contributions made
      by the various researchers in the frontier areas energetic ballistic modifiers,
      energetic binders and energetic plasticizers.

PMID- 18061345
TI  - The repeated immobilization stress increases IL-1beta immunoreactivities in only
      neuron, but not astrocyte or microglia in hippocampal CA1 region, striatum and
      paraventricular nucleus.
AB  - The effect of repeated immobilization stress (RIS) on the expression of
      interleukin-1beta (IL-1beta) and types of cells that express IL-1beta in
      hippocampal CA1 region, striatum and paraventricular nucleus (PVN) were
      investigated in ICR mice. The RIS was induced daily for 2h for 4 consecutive
      days. In the immunohistochemical study, RIS increased IL-1beta immunoreactivities
      (IR) in the hippocampal CA1 region and striatum and PVN. The RIS also increased
      glial fibrillary acidic protein (GFAP) IR and complement receptor type 3 (OX-42)
      IR in the hippocampal CA1 regions and striatum but not PVN. In confocal
      immunofluorescence study, the IL-1beta IR increased by RIS were colocalized with
      only NeuN, but not GFAP or OX-42 in the hippocampal CA1 region, striatum and PVN.
      Our results indicate that RIS increases IL-1beta IR on neuron, but not astrocyte
      or microglia in the hippocampal CA1 region, striatum and PVN, suggesting that the
      IL-1beta IR on neuron may play an important role during RIS. In addition, GFAP
      and OX-42 increased by RIS may be involved indirectly in playing another role in
      the hippocampal CA1 region and striatum during RIS.

PMID- 18061346
TI  - Bee venom injection produces a peripheral anti-inflammatory effect by activation
      of a nitric oxide-dependent spinocoeruleus pathway.
AB  - Our recent data, obtained using a zymosan-induced inflammatory air pouch model in
      mice, have demonstrated that subcutaneous bee venom (BV) injection into the hind
      limb selectively activates the contralateral brain stem locus coeruleus (LC) and
      then via a descending noradrenergic pathway and subsequent adrenal medullary
      catecholamine release induces a potent anti-inflammatory effect. While the
      efferent limb of this BV-induced neuroimmune anti-inflammatory pathway is well
      documented, the afferent limb of this pathway is poorly understood. In particular
      the spinal mechanisms involved with BV activation of the LC are currently
      unknown. Spinal nitric oxide (NO) and its synthase (NOS) have been shown to play
      an important role in the transmission and amplification of neuronal information
      from the spinal cord to the brain stem. In the present study we evaluated whether
      spinal NO plays a role in BV-induced LC activation, since we have previously
      shown that LC activation underlies this 'BV-induced anti-inflammatory effect'
      (BVAI) using the mouse air pouch model. Intrathecal (i.t.) pretreatment with l
      nitro arginine methyl ester (l-NAME, non-selective NOS inhibitor), hemoglobin (NO
      scavenger) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, soluble guanylate
      cyclase inhibitor) abolished BVAI on zymosan-induced leukocyte migration into the
      air pouch. Moreover, i.t. injection of l-N-iminoethyl-lysine (l-NIL, inducible
      NOS inhibitor), but not 7-nitroindazole (7-NI, neuronal NOS inhibitor), also
      inhibited BVAI. BV injection significantly increased both the number of Fos
      immunoreactive neurons and tyrosine hydroxylase-Fos double labeling neurons in
      the contralateral LC in zymosan-induced inflamed mice. Importantly this increase
      in Fos expression in the LC was also completely inhibited by i.t. injection of l
      NIL, but not by i.t. injection of 7-NI. Collectively these results indicate that
      spinal NO generated from inducible NOS is involved in the BV-induced LC
      activation that underlies BVAI.

PMID- 18061347
TI  - Ferulic acid attenuated cognitive deficits and increase in carbonyl proteins
      induced by buthionine-sulfoximine in mice.
AB  - beta-Amyloid peptide (Abeta), the major constituent of the senile plaques
      observed in the brains of Alzheimer's disease patients, is cytotoxic to neurons
      and plays a central role in the pathogenesis of this disease. Previous studies
      have suggested that oxidative stress is involved in the mechanisms of Abeta
      induced neurotoxicity in vivo. Here, we used a mouse model of brain dysfunction
      induced by dl-buthionine-(S,R)-sulfoximine (BSO: 3micromol/3microL/mouse,
      i.c.v.), an inhibitor of glutathione synthesis. In the novel object recognition
      test, we found impairments of exploratory preference in the retention trial but
      not the training trial 24h after BSO treatment, suggesting that BSO produces
      cognitive dysfunction in mice. In the forebrain of this model, we observed
      increase in carbonyl protein levels, an index of biochemical oxidative damage of
      proteins, compared to vehicle-treated mice. Pretreatment with ferulic acid
      (5mg/kg, s.c.) once a day for 6 days inhibited the induction of deficits in
      memory and increase in carbonyl protein levels by BSO. These findings suggest
      that pretreatment with FA may attenuate the memory deficits and increase the
      carbonyl protein levels induced by BSO in mice.

PMID- 18061348
TI  - Activation of alpha1-adrenoceptors increases firing frequency through protein
      kinase C in pyramidal neurons of rat visual cortex.
AB  - Properties of repetitive firing, including spike adaptation, are considered to
      play an essential role in controlling neural excitability in the central nervous
      system. Noradrenaline is one of major neurotranmitters that modulate repetitive
      firing in the cerebral cortex. Although activation of beta-adrenoceptors
      increases firing frequency similarly to noradrenaline, it is still controversial
      whether alpha(1)-adrenoceptor activation influences repetitive firing. In the
      present study, we examined the effects of adrenoceptor agonists on firing
      properties and the intracellular mechanism for alpha(1)-adrenoceptor-dependent
      modulation of firing in pyramidal neurons of rat cerebral cortex. In agreement
      with previous reports, bath application of 100microM isoproterenol, a beta
      adrenoceptor agonist, increased firing frequency in response to a long
      intracellular depolarizing current injection. Phenylephrine (100microM), an
      alpha(1)-adrenoceptor agonist, also increased firing rate, which was inhibited by
      100microM prazosin, an alpha1-adrenoceptor antagonist. The extent of increment in
      firing rate is comparable to that induced by isoproterenol. Furthermore,
      phenylephrine's effects on firing properties were mimicked by 2-5microM phorbol
      ester, a protein kinase C (PKC) activator, and pre-application of 10microM
      chelerythrine, a PKC inhibitor, prevented phenylephrine-induced facilitation of
      repetitive firing. These results suggest that phenylephrine has a facilitatory
      effect on repetitive firing through PKC activation.

PMID- 18061349
TI  - The fibroblast growth factor system is downregulated following social defeat.
AB  - The fibroblast growth factor (FGF) system has previously been found to be altered
      in post-mortem brains of individuals with major depressive disorder (MDD). The
      present study tested whether the FGF system is altered following acute social
      defeat. Rats were exposed to four consecutive days of either a social defeat
      paradigm or novel cages. Animals were sacrificed after the last social defeat
      session and gene expression was assessed in the hippocampus by mRNA in situ
      hybridization. Molecular components of the FGF system were significantly
      downregulated following social defeat. Specifically, FGF2 and FGFR1 mRNA
      expression was decreased in various subfields of the hippocampus. Decreased tone
      of the FGF system following an acute social stressor is congruent with human post
      mortem results of FGF system downregulation in depression. These findings suggest
      that modulating the FGF system may have therapeutic value in the treatment of
      MDD.

PMID- 18061350
TI  - Increased pain sensitivity is not a risk factor but a consequence of frequent
      headache: a population-based follow-up study.
AB  - Altered pain sensitivity is believed to play an important role for chronification
      of headache. It has however mainly been evaluated in highly selected patients
      from headache clinics and never in longitudinal studies. The present study is a
      12-year follow-up of a population-based study of primary headache disorders and
      pain perception, combining a diagnostic headache interview with examination of
      muscle tenderness and measurement of pressure pain thresholds in 1000 subjects
      drawn randomly from the general population in Denmark. The aim of the study was
      to explore the cause-effect relationship between the increased pain sensitivity
      and the development of headache. The pressure pain thresholds were normal at
      baseline but had decreased at follow-up in subjects who developed chronic tension
      type headache over the 12-year period (p = 0.025). In subjects who developed
      frequent episodic tension-type headache the tenderness was normal at baseline but
      had increased at follow-up (p < 0.01) while the pain thresholds were normal both
      at baseline and at follow-up. The findings demonstrate that increased pain
      sensitivity is a consequence of frequent tension-type headache, not a risk
      factor, and support that central sensitization plays an important role for the
      chronification of tension-type headache.

PMID- 18061351
TI  - Diffracted phase and amplitude measurements by energy-filtered convergent-beam
      holography (CHEF).
AB  - Interference between transmitted and diffracted disks in convergent-beam electron
      diffraction (CBED) patterns using the CBED+EBI method proposed by Herring et al.
      is explored using different optical configurations on a spherical aberration
      corrected transmission electron microscope equipped with a biprism and imaging
      energy filter: the SACTEM-Toulouse. We will relate the amplitude and phase of
      these interference patterns, which we call convergent-beam holography (CHEF), to
      microscope transfer theory and the complex amplitudes of the diffracted beams.
      Experimental CHEF patterns recorded in the absence of aberration correction will
      be compared with simulations to validate the theory concerning the effect of
      microscope aberrations and current instabilities. Then, using aberration
      correction, we propose a scheme for eliminating the effect of the microscope, so
      that the diffracted amplitudes and phase due to dynamical scattering within the
      specimen can be studied. Experimental results are compared with simulations
      performed using the full dynamical theory. The potential for studying diffracted
      amplitudes and phases using CHEF analysis is discussed.

PMID- 18061353
TI  - In situ measurements and transmission electron microscopy of carbon nanotube
      field-effect transistors.
AB  - We present the design and operation of a transmission electron microscopy (TEM)
      compatible carbon nanotube (CNT) field-effect transistor (FET). The device is
      configured with microfabricated slits, which allows direct observation of CNTs in
      a FET using TEM and measurement of electrical transport while inside the TEM. As
      demonstrations of the device architecture, two examples are presented. The first
      example is an in situ electrical transport measurement of a bundle of carbon
      nanotubes. The second example is a study of electron beam radiation effect on CNT
      bundles using a 200 keV electron beam. In situ electrical transport measurement
      during the beam irradiation shows a signature of wall- or tube-breakdown.
      Stepwise current drops were observed when a high intensity electron beam was used
      to cut individual CNT bundles in a device with multiple bundles.

PMID- 18061354
TI  - Efficacy of thiabendazole, mebendazole, levamisole and ivermectin against gullet
      worm, Gongylonema pulchrum: in vitro and in vivo studies.
AB  - In vitro and in vivo studies were conducted to evaluate the effects of
      thiabendazole, mebendazole, levamisole and ivermectin against Gongylonema
      pulchrum. For in vitro assays, third-stage larvae (L3) incubated with the drugs
      were administered orally to mice and the ability of larvae to invade the gastric
      mucosa of the animals was examined. After incubation, only those larvae treated
      with high concentrations of levamisole (1 and 10 microg/ml) were tightly coiled
      with intestines exhibiting morphological abnormalities. Good dose-response data
      for the drugs tested was observed at the time of worm recovery from mice, with no
      worms recovered at the two highest concentrations of levamisole. In vivo efficacy
      of the drugs against adult worms was evaluated in six groups of three rabbits,
      each of which was infected with 30 L3 of G. pulchrum and treated with
      thiabendazole at 100 mg/kg for 3 days, mebendazole at 70 mg/kg for 3 days,
      levamisole as a single dose of 8 mg/kg, and subcutaneously injected ivermectin as
      a single dose of 0.2 mg/kg or vehicles of the drugs (control) at 4 months post
      infection. Necropsy 14 days after treatment revealed that levamisole, mebendazole
      and ivermectin reduced worm burdens by 63.2%, 22.8% and 25.8%, respectively, with
      no reductions in worms observed with thiabendazole. The surviving worms were
      principally found in the esophagus with the remainder distributed among the
      buccal mucosa, the tongue, and/or pharyngeal mucosa in all groups. A number of
      morphologically abnormal eggs were observed within the uterus and ovijector in
      female worms recovered from the thiabendazole-treated group. These findings
      suggest that levamisole exhibits in vivo efficacy against G. pulchrum infection
      and that the larval invasion tests using mice could be used to screen for
      anthelmintic susceptibility of nematodes.

PMID- 18061355
TI  - The effect of water and shampooing on the efficacy of a pyriprole 12.5% topical
      solution against brown dog tick (Rhipicephalus sanguineus) and cat flea
      (Ctenocephalides felis) infestations on dogs.
AB  - The efficacy of a single treatment with a 12.5% pyriprole spot-on formulation
      against induced infestations with R. sanguineus ticks and cat fleas (C. felis) as
      well as its persistence after repeated washing and shampooing was investigated in
      four separate studies. In a first study on R. sanguineus involving 32 beagle
      dogs, the efficacy at various time-points during the 30 days that followed
      treatment assessed 48 h after re-infestation ranged from 100% to 99.3%. No
      engorged ticks, alive or dead, were found in the treated animals. Shampooing 2
      days after treatment and weekly washings did not affect the efficacy. In a second
      study on R. sanguineus involving 32 beagle dogs, the efficacy at various time
      points during the 30 days that followed treatment assessed 48 h after re
      infestation ranged from 100% to 96.8%. Single washing 8h after treatment and
      single shampooing 24 h after treatment had no negative impact on the efficacy of
      the product. In a third study on C. felis involving 28 beagle dogs, the efficacy
      at various time-points during the 30 days that followed treatment assessed 48 h
      after re-infestation was always 100% and weekly washings did not diminish the
      efficacy. In a last study on C. felis involving 24 beagle dogs, the efficacy at
      various time-points during the 5 weeks that followed treatment assessed 48 h
      after re-infestation ranged from 100% to 99.8%, and shampooing 24 h after
      treatment did not reduce the efficacy. The product was well tolerated by the
      dogs.

PMID- 18061356
TI  - New research findings on zoledronic acid: survival, pain, and anti-tumour
      effects.
AB  - OBJECTIVES: To summarize the current evidence for clinical, anti-tumour, and
      survival benefits from zoledronic acid in patients with genitourinary cancers.
      METHODS: Studies were identified through MEDLINE searches, review of
      bibliographies of relevant articles, and review of abstracts from scientific
      meetings. RESULTS: Among patients with bone metastases from prostate cancer or
      renal cell carcinoma, zoledronic acid significantly delayed the onset and reduced
      the incidence of skeletal complications compared with placebo. Zoledronic acid is
      also the only bisphosphonate that has demonstrated a trend toward improved
      survival and delayed progression of bone lesions in patients with urologic
      malignancies. Furthermore, zoledronic acid reduced the incidence of pathologic
      fracture, a skeletal-related event known to be associated with reduced survival.
      Bisphosphonates have also demonstrated significant palliative benefits, and
      preclinical evidence indicates that bisphosphonates may have direct anti-tumour
      effects. CONCLUSIONS: Zoledronic acid is the only bisphosphonate that has
      demonstrated statistically significant, long-term clinical benefits through the
      prevention and delay of skeletal-related events in patients with metastatic
      prostate cancer or renal cell carcinoma.

PMID- 18061357
TI  - A role for protein kinase A and protein kinase M zeta in muscarinic acetylcholine
      receptor-initiated persistent synaptic enhancement in rat hippocampus in vivo.
AB  - Antagonists at presynaptic muscarinic autoreceptors increase endogenous
      acetylcholine (ACh) release and enhance cognition but little is known regarding
      their actions on plasticity at glutamatergic synapses. Here the mechanisms of the
      persistent enhancement of hippocampal excitatory transmission induced by the
      M2/M4 muscarinic ACh receptor antagonist methoctramine were investigated in vivo.
      The persistent facilitatory effect of i.c.v. methoctramine in the CA1 region of
      urethane-anesthetized rats was mimicked by gallamine, an M2 receptor antagonist,
      supporting a role for this receptor subtype. Neither the N-methyl-D-aspartate
      (NMDA) receptor antagonists D-(-)-2-amino phosphonopentanoic acid (d-AP5) and
      memantine, nor the metabotropic glutamate receptor subtype 1a antagonist (S)-(+)
      alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385) significantly
      affected the methoctramine-induced persistent synaptic enhancement, indicating a
      lack of requirement for these glutamate receptors. The selective kinase
      inhibitors Rp-adenosine-3', 5'-cyclic monophosphorothioate (Rp-cAMPS) and the
      myrostylated pseudosubstrate peptide, Myr-Ser-Ile-Tyr-Arg-Arg-Gly-Ala-Arg-Arg-Trp
      Arg-Lys-Leu-OH (ZIP), were used to investigate the roles of protein kinase A
      (PKA) and the atypical protein kinase C, protein kinase Mzeta (PKM zeta),
      respectively. Remarkably, pretreatment with either agent prevented the induction
      of the persistent synaptic enhancement by methoctramine and post-methoctramine
      treatment with Rp-cAMPS transiently reversed the enhancement. These findings are
      strong evidence that antagonism of M2 muscarinic ACh receptors in vivo induces an
      NMDA receptor-independent persistent synaptic enhancement that requires
      activation of both PKA and PKM zeta.

PMID- 18061358
TI  - The neural circuitry underlying reinstatement of heroin-seeking behavior in an
      animal model of relapse.
AB  - Reinstatement of extinguished drug-seeking has been utilized in the study of the
      neural substrates of relapse to drugs of abuse, particularly cocaine. However,
      limited studies have examined the circuitry that drives the reinstatement of
      heroin-seeking behavior in the presence of conditioned cues, or by heroin itself.
      In order to test the hypothesis that the circuitry underlying reinstatement in
      heroin-experienced animals would show overlapping, yet distinct differences from
      cocaine-experienced animals, we used transient inhibition of several cortical,
      striatal, and limbic brain regions during reinstatement of heroin-seeking
      produced by heroin-paired cues, or by a single priming dose of heroin. Rats lever
      pressed for i.v. heroin discretely paired with a conditioned stimulus (CS) during
      daily 3-h sessions for a period of 2 weeks, followed by daily extinction of lever
      responding. Subsequent reinstatement of heroin-seeking was measured as lever
      responding in the absence of heroin reinforcement. The first set of reinstatement
      tests involved response-contingent CS presentations following bilateral
      intracranial infusion of either a combination of GABA receptor agonists (baclofen
      muscimol, B/M) or vehicle (saline) into one of 13 different brain regions. The
      second set of reinstatement tests involved a single heroin injection (0.25 mg/kg,
      s.c.) following either B/M or vehicle infusions. Our results showed that vehicle
      infused animals reinstated to both CS presentations and a priming injection of
      heroin, while B/M inactivation of several areas known to be important for the
      reinstatement of cocaine-seeking also attenuated heroin-seeking in response to CS
      presentations and/or a priming dose of heroin. However, as predicted,
      inactivation of areas previously shown to not affect cocaine-seeking
      significantly attenuated heroin-seeking, supporting the hypothesis that the
      circuitry underlying the reinstatement of heroin-seeking is more diffusely
      distributed than that for cocaine.

PMID- 18061359
TI  - Time-course and characterization of orolingual motor deficits in B6SJL-Tg(SOD1
      G93A)1Gur/J mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease
      affecting upper and lower motor neurons. Symptom onset may occur in the muscles
      of the limbs (spinal onset) or those of the head and neck (bulbar onset). Bulbar
      involvement is particularly important in ALS as it is associated with increased
      morbidity and mortality. The purpose of this study was to characterize bulbar
      motor deficits in the B6SJL-Tg(SOD1-G93A)1Gur/J (SOD1-G93A) mouse model of
      familial ALS. We measured orolingual motor function by placing thirsty mice in a
      customized operant chamber that allows for measurement of tongue force and lick
      rhythm as animals lick water from an isometric disc. Testing spanned the pre
      symptomatic, symptomatic, and end-stage segments of the disease. Rotarod
      performance, fore- and hindlimb grip strength, and locomotor activity were also
      monitored regularly during this period. We found that spinal involvement was
      apparent first, with both fore- and hindlimb grip strength being affected in SOD1
      G93A mice from the onset of testing (64 days of age). Rotarod performance was
      affected by 71 days of age. Locomotor activity was not affected, even near end
      stage. Bulbar involvement appeared much later, with tongue motility being
      affected by 100 days of age. Tongue force was affected by 115 days of age. To our
      knowledge, these findings are the first to describe the onset of bulbar versus
      spinal motor signs and characterize orolingual motor deficits in this preclinical
      model of ALS.

PMID- 18061360
TI  - Effects of letrozole on hippocampal and cortical catecholaminergic
      neurotransmitter levels, neural cell adhesion molecule expression and spatial
      learning and memory in female rats.
AB  - We have investigated effects of letrozole, an aromatase inhibitor, on spatial
      learning and memory, expression of neural cell adhesion molecules (NCAM) and
      catecholaminergic neurotransmitters in the hippocampus and cortex of female rats.
      In the intact model, adult Sprague-Dawley rats were divided into four groups
      (n=8). Control received saline alone. Letrozole was administered to the animals
      in the second and third groups by daily oral gavage at 0.2 and 1 mg/kg doses,
      respectively, for 6 weeks. Another group of letrozole-treated rats was allowed to
      recover for 2 weeks. In the second model, 24 rats were ovariectomized (ovx) and
      the first group served as control. The second group received letrozole (1 mg/kg)
      for 6 weeks. Ovx rats in the third group were given letrozole (1 microg/kg) plus
      estradiol (E(2)) (10 microg/rat). At the end, all rats were tested in a spatial
      version of the Morris water maze. Then they were decapitated and the brains
      rapidly removed. Catecholamine concentrations were determined by high performance
      liquid chromatography with electrochemical detection. NCAM 180, 140 and 120
      isoforms were detected by Western blotting. Uterine weights were significantly
      reduced by letrozole in a dose-dependent manner (P<0.01) which returned to
      control values following 2 weeks of recovery (P<0.05). Serum E(2) levels followed
      a similar course (P<0.01). Although improvement in spatial learning performance
      of letrozole-treated rats was not statistically significant, the high-dose
      letrozole-treated group remained significantly longer in the target quadrant
      compared with the control (P<0.05). Administration of letrozole to ovx animals
      significantly reduced the latency (P<0.001) and increased the probe trial
      performance compared with ovx controls (P<0.05). Letrozole increased expression
      of NCAM 180 and NCAM 140 in both hippocampus and cortex of intact rats. In the
      cortex samples of ovx animals, NCAM 180 was overall lower than the intact control
      values (P<0.05). Noradrenaline, dopamine and their metabolites were decreased in
      the hippocampus of the letrozole-treated group (P<0.01). Letrozole had
      differential effects on noradrenaline and dopamine content in the cortex. It
      appears that inhibition of estrogen synthesis in the brain may have beneficial
      effects on spatial memory. We suggest that structural changes such as NCAM
      expression and catecholaminergic neurotransmitters in the hippocampus and
      prefrontal cortex may be the neural basis for estrogen-dependent alterations in
      cognitive functions.

PMID- 18061361
TI  - Use of a new polyclonal antibody to study the distribution and glycosylation of
      the sodium-coupled bicarbonate transporter NCBE in rodent brain.
AB  - NCBE (SLC4A10) is a member of the SLC4 family of bicarbonate transporters,
      several of which play important roles in intracellular-pH regulation and
      transepithelial HCO(3)(-) transport. Here we characterize a new antibody that was
      generated in rabbit against a fusion protein consisting of maltose-binding
      protein and the first 135 amino acids (aa) of the N-terminus of human NCBE.
      Western blotting--both of purified peptides representing the initial
      approximately 120 aa of the transporters and of full-length transporters
      expressed in Xenopus oocytes--demonstrated that the antibody is specific for NCBE
      versus the two most closely related proteins, NDCBE (SLC4A8) and NBCn1 (SLC4A7).
      Western blotting of tissue in four regions of adult mouse brain indicates that
      NCBE is expressed most abundantly in cerebral cortex (CX), cerebellum (CB) and
      hippocampus (HC), and less so in subcortex (SCX). NCBE protein was present in CX,
      CB, and HC microdissected to avoid choroid plexus. Immunocytochemistry shows that
      NCBE is present at the basolateral membrane of embryonic day 18 (E18) fetal and
      adult choroid plexus. NCBE protein is present by Western blot and
      immunocytochemistry in cultured and freshly dissociated HC neurons but not
      astrocytes. By Western blot, nearly all NCBE in mouse and rat brain is highly N
      glycosylated (approximately 150 kDa). PNGase F reduces the molecular weight (MW)
      of natural NCBE in mouse brain or human NCBE expressed in oocytes to
      approximately the predicted MW of the unglycosylated protein. In oocytes,
      mutating any one of the three consensus N-glycosylation sites reduces
      glycosylation of the other two, and the triple mutant exhibits negligible
      functional expression.

PMID- 18061363
TI  - Differences among Black and White young adults on prior attempts and motivation
      to help a smoker quit.
AB  - This study assessed differences between Black and White young adults on prior
      attempts and motivation to help a smoker quit. A total of 1,621 undergraduates
      (912 Black, 709 White; 63% female) ages 18-24 years completed a cross-sectional
      survey. Overall, 54% reported they had previously tried to help someone else stop
      smoking (52% among Blacks vs. 58% among Whites, p=0.016). Among nonsmokers who
      indicated they were close to a smoker whom they thought should quit, Blacks were
      most often concerned about a family member whereas Whites endorsed concern most
      often for a friend (p<0.001). Blacks were more likely than Whites to indicate
      interest in learning ways to help this smoker to quit (p<0.001) but there was no
      significant differences on motivation level (46% of Blacks and 42% of Whites
      reported they were "very" or "extremely" motivated to help this person quit).
      After adjusting for gender, the results remained unchanged. Tobacco control
      efforts could focus on optimizing these supportive behaviors as well as expressed
      motivation and interest in helping a smoker to quit among young adult nonsmokers.

PMID- 18061362
TI  - Identification and treatment of symptoms associated with inflammation in
      medically ill patients.
AB  - Medically ill patients present with a high prevalence of non-specific comorbid
      symptoms including pain, sleep disorders, fatigue and cognitive and mood
      alterations that is a leading cause of disability. However, despite major
      advances in the understanding of the immune-to-brain communication pathways that
      underlie the pathophysiology of these symptoms in inflammatory conditions, little
      has been done to translate this newly acquired knowledge to the clinics and to
      identify appropriate therapies. In a multidisciplinary effort to address this
      problem, clinicians and basic scientists with expertise in areas of inflammation,
      psychiatry, neurosciences and psychoneuroimmunology were brought together in a
      specialized meeting organized in Bordeaux, France, on May 28-29, 2007. These
      experts considered key questions in the field, in particular those related to
      identification and quantification of the predominant symptoms associated with
      inflammation, definition of systemic and central markers of inflammation,
      possible domains of intervention for controlling inflammation-associated
      symptoms, and relevance of animal models of inflammation-associated symptoms.
      This resulted in a number of recommendations that should improve the recognition
      and management of inflammation-associated symptoms in medically ill patients.

PMID- 18061364
TI  - (-)-Epigallocatechin-3-gallate downregulates estrogen receptor alpha function in
      MCF-7 breast carcinoma cells.
AB  - BACKGROUND: (-)-Epigallocatechin-3-gallate (EGCG) is the most active catechin
      present in green tea, demonstrated to have chemopreventive action and to kill
      cancer cells selectively. As a previous study found that catechins could compete
      with 17-beta-estradiol for binding to estrogen receptor alpha (ERalpha), we asked
      whether EGCG could regulate ERalpha action. METHODS: We used MCF-7, a breast
      carcinoma cell line having a high level of ERalpha expression. The cells were
      treated with various EGCG concentrations and cell viability was evaluated by MTT
      assay. ERalpha and pS2 expression were analyzed by RT-PCR after RNA extraction.
      To better define EGCG action in relation to ERalpha, we studied EGCG cytotoxicity
      on MCF-7 resistant to tamoxifen (MCF-7tam), MCF-7 treated with 10(-7)M ICI
      182,780 for 8 days and on MDA-MB-231, a cell line that lacked ERalpha by flow
      cytometry (FCM). RESULTS: Both ERalpha and pS2 mRNA were expressed in samples
      treated with low EGCG concentration (30 microg/ml). At this concentration, no
      cell change was detectable. In contrast, pS2 expression was lost in samples
      treated with 100 microg/ml EGCG for 24h, indicating ERalpha alteration. EGCG
      cytotoxicity was lower when ERalpha was not present (MDA-MB-231) or inactivated
      (by tamoxifen or ICI 182,780). CONCLUSIONS: Functionally active ERalpha may have
      a role in EGCG cytotoxicity, increasing the sensitivity to the drug. As higher
      EGCG concentrations also killed cells resistant to tamoxifen or treated by 10(
      7)M ICI 182,780, EGCG ought to be better investigated in breast carcinoma cells
      treated with drugs targeted to steroid receptors, as a potential complement of
      therapy.

PMID- 18061365
TI  - The information-theory analysis of Michaelis-Menten constants for detection of
      breast cancer.
AB  - BACKGROUND: The Michaelis-Menten constants (K(m) and V(max)) operated by the
      Information Theory were employed for detection of breast cancer. METHODS: The
      rate of enzymatic hydrolysis of fluorescein diacetate (FDA) in live peripheral
      blood mononuclear cells (PBMC), derived from healthy subjects and breast cancer
      (BC) patients, was assessed by measuring the fluorescence intensity (FI) in
      individual cells under incubation with either the mitogen phytohemagglutinin
      (PHA) or with tumor tissue, as compared to control. The data were processed by
      the Information Theory to determine the parameters and test conditions, which can
      best discriminate between the different groups. The normalized mutual information
      (uncertainty coefficients) was used as the measure of correlation/discrimination.
      RESULTS: An estimated general correlation was established between the K(m)/V(max)
      parameters and the examined patterns in the different bioassays. The information
      theoretical analysis revealed the relative diagnostic value of each parameter.
      CONCLUSION: It was found that K(m) and V(max) as individual parameters show
      relatively low correlations with the presence or absence of disease, yet in
      combination often provide a good diagnostic measure. Based on the relative
      diagnostic values of each parameter, a diagnostic decision making rule was
      constructed. The diagnostic rule provided correct diagnosis for 37 out of 40
      subjects.

PMID- 18061366
TI  - Whole genome amplification of DNA extracted from hair samples: potential for use
      in molecular epidemiologic studies.
AB  - BACKGROUND: Because of concerns regarding the quality and quantity of DNA
      isolated from human hair, such samples are often overlooked as a source of DNA
      for molecular epidemiological studies. Nevertheless, there are many potential
      benefits to using hair: it is easily self-collected; it does not require costly
      collection kits; it can be mailed for a nominal fee; and the hair specimens can
      be stored at room temperature. However, the amount of DNA that can be extracted
      from hair samples is somewhat limited. Therefore, we assessed the feasibility of
      using whole genome amplification (WGA) on genomic DNA extracted from archived
      human hairs (stored for 7 to 11 years) to increase the quantity of DNA available
      for genotyping analysis. METHODS: We evaluated two methods of WGA, multiple
      displacement amplification and the Genomeplex method. Both WGA methods were
      performed on each of 44 DNA samples isolated from archived human hair specimens.
      The resulting WGA products where then screened for the presence of three single
      nucleotide polymorphisms. The genotyping results were compared to genotyping data
      obtained from DNA isolated from mouthwash samples collected from the same
      individuals. RESULTS: When we focused on DNA extracted from the hair root, we
      observed excellent agreement between the genotypes determined from both the hair
      (pre-WGA) samples and Genomeplex WGA when compared to their corresponding
      mouthwash DNA samples (kappa=0.83-0.91 and 0.79-0.92, respectively); whereas the
      agreement between the MDA samples and mouthwash DNA samples was poor (kappa=0.27
      0.51). CONCLUSIONS: Our data suggest that, when combined with Genomeplex WGA,
      hair specimens containing the root portion can serve as a reliable and renewable
      source of DNA.

PMID- 18061367
TI  - Cancer screening knowledge, attitudes, and behaviors among culturally Deaf
      adults: implications for informed decision making.
AB  - BACKGROUND: Previous studies show that Deaf persons tend to have lower health
      status, lack health knowledge, have differing health attitudes, and decreased
      health care utilization when compared to the general population. The authors
      sought to examine knowledge, attitudes, and behaviors surrounding age- and gender
      specific cancer screening tests amongst a sample of Deaf adults who were patients
      of Deaf-friendly medical organizations. The authors also sought to compare age-
      and gender-specific cancer screening rates amongst this sample to that of the
      general US population. METHODS: A sample of 203 adult Deaf patients participated
      in a comprehensive, face-to-face health survey conducted between November 2002
      and March 2003. The survey was administered in American Sign Language by Deaf
      interviewers and included age- and gender-specific cancer knowledge, attitude,
      and behavior questions. RESULTS: Knowledge pertaining to Pap smear among females
      was low, while the proportion having ever had a Pap smear was comparable to the
      general population. Mammography knowledge amongst females age 50 and older was
      comparatively higher, although it remained lower than the proportion of females
      in this age group who reported ever receiving a mammogram. Overall, screening
      rates for breast, cervical, and colorectal cancer were similar to rates in the
      general US population. Attitudes toward specific cancer screening tests were also
      favorable. CONCLUSIONS: Persons within the Deaf community can have cancer
      screening rates similar to those of the general US population. However,
      utilization in the absence of knowledge regarding these tests is worrisome and
      brings about ethical, health care quality and health education concerns.

PMID- 18061368
TI  - Assessing perceptions of cancer risk: does mode of assessment or numeracy matter?
AB  - BACKGROUND: Many existing models of health behavior advance perceived risk for
      disease as a key motivator of risk-reduction behavior. Thus evaluating contextual
      factors that may influence assessment of perceived risk is important. We examined
      (1) how mode of assessment (mail, telephone, web-based) and numeracy affect
      reported estimates of perceived risk of colon cancer, and (2) how the amount of
      missing perceived risk data differs as a function of mode of assessment and
      numeracy. METHOD: Women (N=457; mean age=61.3 years) with and without Internet
      access participated. Women without Internet access (n=233) were randomized into
      telephone or mail modes of assessment, and women with Internet access (n=224)
      were randomized into telephone, mail, or web-based modes of assessment. Numeracy
      and four different estimates of perceived lifetime risk for colon cancer
      (personal percentage, population percentage, comparative, binary) were assessed.
      RESULTS: No significant differences were found in obtained risk estimates for any
      of the four risk perception items across the different modes of assessment.
      Greater numeracy was associated with lower percentage estimates of perceived
      risk. In general, the telephone mode of assessment yielded less missing data than
      the mail mode of assessment. CONCLUSION: Mode of assessment largely does not
      matter when it comes to assessing perceived colon cancer risk. However, numeracy
      does matter and specifically impacts percentage estimates of perceived risk.
      While web-based, mail, and telephone modes may be used interchangeably when
      assessing perceived cancer risk; less missing data may result with telephone data
      collection.

PMID- 18061369
TI  - Risk perception among women receiving genetic counseling: a population-based
      follow-up study.
AB  - BACKGROUND: We aimed to explore the impact of genetic counseling on perceived
      personal lifetime risk of breast cancer, the accuracy of risk perception, and
      possible predictors of inaccurate risk perception 1 year following counseling.
      METHODS: We conducted a population-based prospective follow-up study of 213 women
      who received genetic counseling for hereditary breast and ovarian cancer, 319
      women who underwent mammography (Reference Group I), and a random sample of 1070
      women from the general population (Reference Group II). RESULTS: Women who
      received genetic counseling decreased their perceived risk by an average of 6.6
      percentage points (95% CI: 3.0%; 10.2%) between baseline and 12 months of follow
      up. In contrast, perceived risk remained relatively stable in the reference
      groups. The proportion of women who accurately perceived their risk increased by
      16% in the group receiving genetic counseling, compared to a reduction of 5%
      (p=0.03) and 2% (p=0.01) in Reference Groups I and II, respectively. Risk
      communicated only in words, inaccurate risk perception at baseline, and presence
      of a familial mutation appeared to be predictors of inaccurate risk perception 12
      months after counseling. CONCLUSION: This population-based study of women with a
      family history of breast or ovarian cancer indicates that genetic counseling can
      help them both to reduce their perceived risk and to achieve a more realistic
      view of their risk of developing breast cancer.

PMID- 18061370
TI  - Prevalence and predictors of comorbid diabetes among newly diagnosed Hispanic
      cancer patients in Connecticut.
AB  - BACKGROUND: U.S. Hispanics are at elevated risk of diabetes, and comorbid
      diabetes has been associated with poorer prognosis among patients with certain
      cancers. This study examined prevalence and predictors of comorbid diabetes in
      newly diagnosed Hispanic cancer patients in Connecticut. METHODS: For all
      Hispanic patients diagnosed (at age 10+ years) with cancer in 2002-2003 and
      reported to the population-based Connecticut cancer registry, information from
      hospital medical records in the state was sought for comorbid diabetes (i.e., in
      any hospital admission 12 months prior to cancer diagnosis) and its treatment,
      body weight and height, preferred or primary language, and type of health
      insurance. Multiple logistic regression (MLR) models were used to examine
      predictors of presence of comorbid diabetes. RESULTS: Comorbid diabetes was found
      for 192 (25.1%) of 765 patients, and was statistically significantly associated
      with preferred language (30.3% of 535 with non-English vs. 15.1% of 166 with
      English), age, and body mass index in a MLR model. Type of diabetes treatment was
      found for 92% of the 192 patients with diabetes. CONCLUSIONS: The high prevalence
      of comorbid diabetes among newly diagnosed Hispanic cancer patients, especially
      those without English as their preferred language, should be an impetus to
      further research on quality of diabetes care and survival of these patients.

PMID- 18061371
TI  - Horner's syndrome as an initial sign of metastatic breast cancer: case report.
AB  - BACKGROUND: Horner syndrome is caused by a lesion affecting the sympathetic
      innervation of the lids and pupil. The most common factor producing the
      preganglionic Horner's syndrome is malignant tumors. METHODS: We report here a
      case of Horner syndrome in young women with the history of breast cancer. The
      patient underwent extensive neurological examinations, including MRI of head and
      neck, together with chest radiograph and CT thorax scan. RESULTS: Present
      radiographic methods revealed one-sided metastatic pleural effusion as a cause of
      sympathetic lesion. CONCLUSION: Metastatic breast disease usually affects lungs,
      bone, liver, adrenals and skin, and it is highly unusual for ocular involvement
      to be the first sign of its existence. This report presents a rare case of
      pleural metastatic breast cancer causing Horner's syndrome/Pancoast syndrome
      without lung involvement.

PMID- 18061372
TI  - Associations between timing of exposure to ultraviolet radiation, T-stage and
      survival in prostate cancer.
AB  - BACKGROUND: Exposure to ultraviolet radiation (UVR) has been inversely associated
      with prostate cancer risk. We determined if skin type and UVR exposure are linked
      with parameters of prostate cancer outcome. METHODS: We used a questionnaire to
      determine UVR exposure parameters and skin type in 553 men with prostate cancer
      and, using logistic regression and survival analysis, studied their association
      with T-stage, Gleason score, and survival after starting hormone manipulation
      therapy. RESULTS: UVR exposures 10, 20, and 30 years before diagnosis were
      inversely associated with T-stage. The odds ratio (OR) for UVR exposure 10 years
      before diagnosis was lowest (OR=0.69, 95% CI=0.56-0.86). ORs were lower in men
      with skin types I/II than III/IV. Skin types I/II were associated with longer
      survival after commencing hormone therapy (hazard ratio=0.62, 95% CI=0.40-0.95).
      CONCLUSIONS: Our finding that UVR exposure is beneficial is compatible with
      accumulating data showing sunlight has a protective effect on disease phenotype.

PMID- 18061373
TI  - Expression of vascular endothelial growth factors-C and -D correlate with
      evidence of lymphangiogenesis and angiogenesis in pancreatic adenocarcinoma.
AB  - BACKGROUND: We analyzed the intratumoral and peritumoral microvessel density
      (MVD) and microlymphatic vessel density (MLVD) in pancreatic adenocarcinoma (PAC)
      and recorded the expression of vascular endothelial growth factor (VEGF)-C and 
      D. These data were tested for their significance for tumor progression. METHODS:
      The tissue samples were obtained from 30 patients with PAC. The expression of
      VEGF-C and -D, MLVD, MVD was assayed by immunohistochemical staining. The
      expression of VEGF-A and -C, and -D mRNA was detected by semi-quantitative RT
      PCR. RESULTS: Immunohistochemical analysis revealed the presence of VEGF-C and -D
      immunoreactivity in 73% (22/30) and 57% (17/30). The positive rates of VEGF-C and
      -D protein in central portion of tumors (30% and 16.7%) were significantly lower
      than those in marginal portion (73.3% and 56.7%). The group with high expression
      of VEGF-C and -D in marginal portion had higher incidence of lymph node
      metastasis, lymphatic invasion and venous invasion. The MLVD in both of the VEGF
      C and -D positive groups was higher than that in the negative groups, and the
      lymph node metastasis increased. MVD in the VEGF-C positive group was higher than
      that in the negative group. CONCLUSIONS: The expression of VEGF-C and -D in the
      marginal portion of tumor significantly associated with lymphatic metastasis and
      prognosis in patients with PAC, and may induced lymphangiogenesis. VEGF-C was
      important in the regulation of angiogenesis and lymphangiogenesis in PAC.

PMID- 18061374
TI  - A nested case-control study of stomach cancer incidence and serum superoxide
      dismutase activity in the Japan Collaborative Cohort study in Japan.
AB  - BACKGROUND: We conducted a nested case-control study to investigate the
      association between serum levels of superoxide dismutase (SOD) enzyme and the
      incidence of stomach cancer. METHODS: A nested case-control study was established
      within the Japan Collaborative Cohort Study. The follow-up period was from 1988
      through 1997. Newly diagnosed cases of stomach cancer were recorded in 804
      subjects, of these sera were available for 161 cases. Each of these cases was
      matched on study area, gender and baseline age with two controls; giving 161
      stomach cancer cases and 314 control subjects for analysis. Serum levels of SODs
      were divided into quartiles, with the first quartile used as the reference. Odds
      ratios (ORs) and 95% confidence interval (95% CI) for the other serum level
      quartiles were estimated using the conditional logistic model. RESULTS: The
      adjusted ORs and 95% CI for the second, third, and fourth SOD quartiles were 0.71
      (95% CI: 0.42-1.19), 0.59 (95% CI: 0.32-1.10), and 0.86 (95% CI: 0.48-1.54),
      respectively. CONCLUSION: We found no association between SOD serum level and the
      risk of stomach cancer. The role of SOD in the development of stomach cancer
      requires further investigation.

PMID- 18061375
TI  - Shoaling in juvenile guppies: the effects of body size and shoal size.
AB  - While factors affecting shoal mate choice have been examined extensively in adult
      guppies (Poecilia reticulata), few studies have focused on the shoaling behavior
      of juveniles. In this study, juvenile guppies were tested for their ability to
      shoal as well as their response to shoal mates of different body size and to
      shoals with different numbers of individuals. In dichotomous choice tests, 10-day
      old guppies (mean body length=8.83 mm), 30-day-old guppies (13.17 mm) and 50-day
      old guppies (18.6mm) were given the opportunity to swim near shoals of five fish
      or an empty chamber. In most cases, the juvenile fish demonstrated shoaling
      behavior, swimming near a group of fish rather than an empty chamber, regardless
      of the age of the stimulus shoal. When presented with two shoals, one of similar
      age and body size and one of dissimilar age and body size, only the 50-day-old
      guppies showed a significant preference for the age-matched shoal. Similarly,
      when choosing between a large shoal and a small shoal, only the 50-day-old
      guppies spent significantly more time near the larger shoal. Thus, while
      juveniles at each age shoaled, only 50-day-old fish demonstrated the shoal mate
      discrimination seen in adult fish.

PMID- 18061376
TI  - Dogs as vectors of Streptobacillus moniliformis infection?
AB  - Rat bite fever is a bacterial zoonosis transmitted through the bite of rats. One
      of the two etiological agents that cause rat bite fever is Streptobacillus
      moniliformis. Rat bite fever is rare and very likely under diagnosed but occurs
      worldwide. Other animals, like dogs and cats that have mouthed a rat are often
      mentioned in the literature as potential risks for the attraction of rat bite
      fever. However, rat bite fever caused by the bite of a dog or cat has very seldom
      been documented. Therefore, to identify the possible risk for humans to become
      infected with S. moniliformis after having been bitten by a dog that has been in
      contact with rats, the presence of S. moniliformis in the mouth of these dogs was
      tested with molecular methods. Swabs taken from the mouth of 18 dogs with proven
      contacts with rats were tested for the presence of S. moniliformis DNA by PCR. An
      amplicon of the right size was obtained in 10 of the 18 dogs. Nucleotide
      sequencing of five amplicons of PCR positive samples demonstrated the presence of
      S. moniliformis DNA in the mouth of three dogs. A bite by these dogs therefore
      might infect humans with S. moniliformis and cause rat bite disease.

PMID- 18061377
TI  - Diagnostic and typing options for investigating diseases associated with
      Pasteurella multocida.
AB  - Pasteurella multocida is responsible for major animal diseases of economic
      significance in both developed and developing countries whereas human infections
      related to this bacterium are infrequent. Significantly, development of a carrier
      status or latent infections plays a critical role in the epidemiology of these
      diseases. Aiming at increased knowledge of these infections, we examine potential
      diagnostic and selected typing systems for investigating diseases caused by P.
      multocida. Detection of P. multocida from clinical specimen by; (i) isolation and
      identification, (ii) polymerase chain reaction (PCR), iii) specific hybridisation
      probes, (iv) serological tests and (v) other alternative methods is critically
      evaluated. These detection systems provide a wide spectrum of options for rapid
      diagnosis and for detecting and understanding of latent infections in herd/flock
      health control programmes, though PCR methods for detecting P. multocida in
      clinical specimen appear increasingly preferred. For establishing the clonality
      of outbreak strains, we select to discuss macromolecular profiling, serotyping,
      biotyping, restriction enzyme analysis, ribotyping and multiplex PCR typing.
      Although P. multocida infections can be rapidly diagnosed with molecular and
      serological tests, isolation and accurate species identification are central to
      epidemiological tracing of outbreak strains. Our review brings together
      comprehensive and essential information that may be adapted for confirming
      diagnosis and determining the molecular epidemiology of diseases associated with
      P. multocida.

PMID- 18061378
TI  - Screening poly(ethyleneglycol) micro- and nanogels for drug delivery purposes.
AB  - This study investigates poly(ethyleneglycol) (PEG)-based micro- and nanogels,
      with or without lipid coating, with the aim to slowly deliver encapsulated
      molecules. Hydroxyethylmethacrylated PEG (PEG-HEMA), PEG-HEMA with an oligo
      lactate spacer (PEG-lac-HEMA), and eight-armed PEG end capped with HEMA (* -PEG
      HEMA) were used. PEG-lac-HEMA matrices degraded very fast (in terms of days),
      while it took about 1 month for linear PEG-HEMA and several months for * -PEG
      HEMA hydrogels to become degraded. PEG-based microgels were made by use of an all
      aqueous technique and could be lipid-coated by mixing the microgels (made
      positively or negatively charged through copolymerization with respectively
      methacrylic acid and dimethyl aminoethyl methacrylate with a suspension of
      oppositely charged liposomes. The release of fluorescently labeled molecules
      incorporated in the PEG-based microgels could be clearly governed by the type of
      molecules used (lasting from hours to months). PEG-based nanogels could be made
      using liposomes as a nanoscopic mold, resulting in particles with a PEG gel core
      surrounded by a lipid coating. BSA could be easily encapsulated in the PEG
      nanogels which released the BSA over a period of about 1 week.

PMID- 18061379
TI  - Thermal behavior of water in the selected starch- and cellulose-based polymeric
      hydrogels.
AB  - In a polymer-water matrix, freezable water is depressed due to either porosity
      confinement or interaction. The aim of the study was to examine water
      crystallization/melting depression by sub-ambient differential scanning
      calorimetry. The selected starch- and cellulose-based polymers including pre
      gelatinized starch (PS), sodium alginate, sodium starch glycolate,
      hydroxypropylmethyl cellulose (HPMC), sodium carboxymethyl cellulose, and
      croscarmellose sodium were employed. The pre-treated with ambient humidity (85
      100% relative humidity, at 30.0+/-0.2 degrees C for 10 days) and with excess
      water (hydrogels) samples were subjected to between 25 and -150 degrees C cooling
      heating cycle at 5.00 degrees C/min rate. The volume fractions of hydrogels were
      measured by light scattering technique. It was observed that all polymers but PS
      and HPMC with ambient humidity presented freezable water in two distinct
      fractions namely bound water where crystallizing/melting temperature was
      depressed and bulk water. The water transition in samples with various contents
      exhibited the pattern as a polymer solution, thus rather than confinement, the
      depression was due to interaction. The volume fraction-melting temperature data
      derived from endotherms of hydrogels were successfully fitted to Flory's model
      (r(2): 0.934-0.999). The Flory's interaction parameters (chi(1)) were found to
      vary between 0.520 and 0.847. In addition, the smaller the value of chi(1), the
      larger melting was depressed, i.e., stronger affinity for water.

PMID- 18061380
TI  - Physicochemical properties of tamoxifen hemicitrate sesquihydrate.
AB  - A novel modification of tamoxifen [(Z)-2-[4-(1,2-diphenyl-1-butenyl) phenoxy]-N,N
      dimethylethylamine] citrate, tamoxifen hemicitrate hydrate was prepared. The
      crystalline form was identified and characterized by powder and single crystal X
      ray diffractometries, differential scanning calorimetry (DSC), thermal
      gravimetric analysis (TGA), and hot-stage microscopy, and its physicochemical
      stability was also evaluated. The results of an elemental analysis, a single
      crystal X-ray analysis, and the TGA suggested that the molar ratio of
      tamoxifen:citric acid:water was 2:1:3 indicating it to be tamoxifen hemicitrate
      sesquihydrate. Simultaneous XRD-DSC measurements also indicated that two
      hydrates, sesquihydrate and hemihydrate, and an anhydrous form would exist during
      heating. The physicochemical stability of tamoxifen citrate forms A and B
      suspended in water and of form A during kneading and drying suggested that
      tamoxifen citrate was transformed into tamoxifen hemicitrate hydrate in water
      within 24 h, whereas tamoxifen citrate in a mixture with microcrystalline
      cellulose was quite stable during kneading. These results suggested that water
      and a mixture of water and organic solvent should be used for the manufacturing
      process with special attention paid to the transformation to tamoxifen
      hemicitrate sesquihydrate, because it showed a different stoichiometry from the
      active ingredient, tamoxifen citrate.

PMID- 18061381
TI  - Release profile comparison and stability of diltiazem-resin microcapsules in
      sustained release suspensions.
AB  - A sustained release suspension of diltiazem, a short half-life calcium channel
      blocker, was developed to reduce frequency of drug administration, ease of dose
      adjustment and improve patient compliance. In this study, the sustained release
      of diltiazem was obtained by complexing the drug with Dowex 50W x 4 and Dowex 50W
      x 8, strong cationic exchange resins with 4% and 8% degree of cross-linking,
      respectively. The diltiazem-Dowex 50W x 4 complexes provided the highest drug
      release and were subsequently used to prepare the microcapsules by emulsion
      solvent evaporation method, using 0.75-5.00% cellulose acetate butyrate (CAB) in
      methylene chloride as a coating solution. As the concentration of CAB increased,
      the size of microcapsule increased and the drug release from the microcapsule was
      retarded. From release profile comparison using f(1) and f(2) factors, it was
      found that the microcapsules coated with 1.75% CAB provided a release profile
      equivalent to the commercial product of diltiazem sustained release capsule,
      Herbesser 90SR. Furthermore, sustained release suspensions of the diltiazem
      microcapsules were formulated with the use of 0.8% sodium carboxymethylcellulose
      or 0.4% xanthan gum as a suspending agent. The suspension of 0.4% xanthan gum
      showed superior in physical appearance after 120-day storage at 30 and 45 degrees
      C. In addition, all sustained release suspensions possessed good stability with
      low drug leaching and their release profiles were unchanged when compared with
      the dried microcapsules for 120 days at 30 and 45 degrees C.

PMID- 18061383
TI  - [What deontological rules to adopt for surveys aimed at research and surveillance
      among children?].

PMID- 18061382
TI  - Antioxidant and mitochondrial protective effects of silibinin in cold
      preservation-warm reperfusion liver injury.
AB  - AIM OF THE STUDY: Silybum marianum (milk thistle) is a Mediterranean plant that
      has been used since Greco-Roman times to treat liver ailments. Silibinin, the
      most active hepatoprotective constituent of the plant's seed, possesses
      antioxidant and anti-inflammatory properties. We thus assessed its protective
      potential in liver transplantation injury. MATERIALS AND METHODS: Rat livers were
      isolated and preserved during 24h at 4 degrees C in University of Wisconsin (UW)
      solution alone (control), UW containing 100 microM silibinin or UW containing
      vehicle (ethanol). Livers were then reperfused at 37 degrees C for 1h with Krebs
      Henseleit solution supplemented with 20% erythrocytes. RESULTS: Compared to
      control, cold preservation and warm reperfusion promoted lipid peroxidation
      (+40%) and superoxide anion generation (+147%), while attenuating reduced
      glutathione (-23%), mitochondrial ATP content (-57%) and respiratory control
      ratio (RCR; -37%). Preservation done in presence of silibinin improved parameters
      affected by preservation and reperfusion. In fact, silibinin promoted an increase
      of ATP and RCR by, respectively, 39 and 16% and decreased oxidative stress to
      values observed in livers never preserved nor perfused. CONCLUSIONS: In
      conclusion, silibinin shows promise in protecting the liver from cold
      preservation/warm reperfusion damages. Moreover our study suggests that concepts
      of traditional medicine have the potential to be transposed successfully in the
      context of modern medical interventions such as liver transplantation surgery.

PMID- 18061384
TI  - [Opinion on the issue: the causes of cancer in France].

PMID- 18061386
TI  - Reconstruction in image space using basis functions for partially parallel
      imaging.
AB  - General theory of a new reconstruction technique for partially parallel imaging
      (PPI) is presented in this study. Reconstruction in Image space using Basis
      functions (RIB) is based on the general principle that the PPI reconstruction in
      image space can be represented by a pixel-wise weighted summation of the aliased
      images directly from undersampled data. By assuming that these weighting
      coefficients for unaliasing can be approximated from the linear combination of a
      few predefined basis functions, RIB is capable of reconstructing the image within
      an arbitrary region. This paper discusses the general theory of RIB and its
      relationship to the classical reconstruction method, GRAPPA. The presented
      experiments demonstrate RIB with several MRI applications. It is shown that the
      performance of RIB is comparable to that of GRAPPA. In some cases, RIB shows
      advantages of increasing reconstruction efficiency, suppressing artifacts and
      alleviating the nonuniformity of noise distribution. It is anticipated that RIB
      would be especially useful for cardiac and prostate imaging, where the field of
      view during data acquisition is required to be much larger than the region of
      interest.

PMID- 18061385
TI  - Drosophila aging 2006/2007.
AB  - Research on aging in Drosophila continues to provide new insights into this
      complex process. Drosophila is highly amenable to study aging because of its
      short generation time, comprehensive resources for genetic manipulation, and
      functionally conserved physiology. Importantly, many of these physiological
      processes such as heart function, sleep, and metabolism functionally senescence
      in older flies. As the evolutionarily conserved insulin and TOR pathways are
      critical regulators of aging, the influence of insulin and TOR signaling on these
      processes is an important area for future research. An important emerging theme
      is determining the age-dependent alterations that occur at the organ level and
      how this functional senescence is regulated by different tissues.

PMID- 18061387
TI  - A rare case of lung coinfection by Streptomyces cinereoruber and Haemophilus
      influenzae in a patient with severe chronic obstructive pulmonary disease:
      characterization at species level using molecular techniques.
AB  - Streptomyces cinereoruber isolated from a patient with severe respiratory failure
      that could not be identified by culture was correctly identified at the species
      level by comparative sequence analysis of 16S rDNA and the hypervariable alpha
      region of 16S rDNA. Restriction fragment length polymorphism, morphologic, and
      biochemical characteristics have confirmed their identity.

PMID- 18061388
TI  - Fluvastatin potentiates the activity of caspofungin against Aspergillus fumigatus
      in vitro.
AB  - Statins (anticholesterol drugs) inhibit HMG-CoA reductase, which is a key rate
      limiting enzyme in the synthesis of sterols in fungi. We therefore investigated
      the in vitro inhibitory activity of various statins against Aspergillus fumigatus
      alone and in combination with antifungal drugs. Fresh conidial suspensions from
      10 clinical isolates of A. fumigatus were obtained. The MIC and minimum
      fungicidal concentration (MFC) were determined by the Clinical and Laboratory
      Standards Institute M-38A protocol and the fungicidal activity by time-kill
      study. Fluvastatin (FST) showed good activity (MIC, 2 mg/L; MFC, 4 mg/L) against
      A. fumigatus; other statins had no activity (MIC > or = 256 mg/L). FST enhanced
      the activity of caspofungin (CFG) against A. fumigatus; subinhibitory
      concentrations of FST in combination with CFG showed >99.9% killing of A.
      fumigatus conidia, whereas either drug alone showed poor activity at
      subinhibitory concentrations. FST potentiated the antifungal activity of CFG but
      displayed no specific interaction with voriconazole or amphotericin B.

PMID- 18061389
TI  - Ambulatory dysfunction due to unrecognized pernicious anemia.
AB  - Pernicious anemia can result in significant hematologic and neurologic
      impairments due to a reduction in cobalamin absorption. Typically thought to be a
      disease of elderly whites, a growing body of literature has documented the
      disease in blacks and in younger age groups. We describe a case of a young black
      woman with gradually progressive lower extremity paresthesias, weakness, and
      ataxia as the primary presenting symptoms of pernicious anemia. This case is
      presented to make emergency physicians aware of pernicious anemia as a cause of
      ambulatory dysfunction in younger patients. We review the current body of
      literature on the diagnosis and management as well as evidence that the
      demographic profile of the disease is changing. Furthermore, in women of
      reproductive age, there is the potential for significant fetal and infant
      morbidity.

PMID- 18061390
TI  - Ablative and catheter-delivered therapies for colorectal liver metastases (CRLM).
AB  - Colorectal liver metastases occur in a significant number of patients with bowel
      cancer. Only a small proportion of patients will be candidates for surgical
      resection and more than 50% of these will develop further metastases. Palliative
      chemotherapy has been the mainstay of treatment for the remainder of patients
      with unresectable disease. Toxicity is common and median survival is in the order
      of 18 months, although this has increased slightly with the addition of
      monoclonal antibodies and angiogenesis inhibitors. Targeted treatment of liver
      metastases with ablative or trans-arterial techniques allows localised, minimally
      invasive therapy without significant toxicity or morbidity. Ablative techniques
      include radiofrequency, microwave, laser and cryotherapy. Catheter-delivered
      trans-arterial treatments include conventional chemoembolisation, drug-eluting
      beads and selective internal radiation spheres. High intensity focussed
      ultrasound is also likely to play a significant role in the future. The
      combination of these treatment options with or without systemic chemotherapy may
      have a synergistic effect. This article will discuss the role and efficacy of
      each of these techniques.

PMID- 18061391
TI  - [Analysis of induced sputum in refractory asthma].
AB  - Induction of sputum by inhalation of hypertonic or isotonic fluid makes possible
      the safe and noninvasive harvesting of airway cells from patients with asthma,
      regardless of disease severity. Analysis of sputum cells has helped to identify
      different phenotypes of refractory asthma and shown that such asthma can be
      eosinophilic, neutrophilic, or both. Elevated eosinophil levels in sputum
      indicate a risk of exacerbation if the corticosteroid dose is reduced in
      stabilized patients. Surveillance of eosinophilia levels as an indicator for
      corticosteroid adjustment in refractory asthma makes it possible to reduce the
      frequency of severe exacerbations.

PMID- 18061393
TI  - [Is asthma still a life-threatening disease?].
AB  - After a substantial augmentation in the mid-1980s, mortality from asthma
      stabilized in France as in the other industrialized countries, probably because
      of ever more appropriate health care utilization and treatment. In 2004, there
      were 1099 death in metropolitan France with a principal cause listed as asthma
      (last published data), for a crude rate of 1.8 deaths per 100,000 inhabitants.
      Despite the fact that fewer people are dying of asthma, several studies show an
      excess of all-cause mortality among people with asthma compared with people
      without asthma. The prevalence of severe asthma does not appear to have
      diminished, and clinical data show that severe asthma remains potentially fatal,
      because of resistant phenotypes, among other reasons. Other investigations are
      necessary to determine the trends in the prevalence of severe asthma and to
      understand the nonrespiratory mortality of asthma patients. Vigilance and
      surveillance of severe asthma must be maintained.

PMID- 18061392
TI  - [Hypovitaminosis D among 18-to-49-years-old women wearing concealing clothes, an
      ignored reality in general practice].
AB  - BACKGROUND: Although the morbidity and mortality of vitamin D deficiency are well
      known in the elderly and among children, doctors are unlikely to consider it as a
      diagnosis in young adults, even when it is symptomatic. Numerous additional
      examinations are thus unnecessarily prescribed, while diagnosis is delayed. After
      observing several cases of severe vitamin D deficiency among women aged 18 to 49
      years who wore concealing clothing, we conducted an investigation of the
      prevalence of this vitamin deficiency in this community. We asked ourselves 2
      questions: What proportion of women in this population has a vitamin D deficiency
      and how severe is it? Are general practitioners (GPs) aware of this problem?
      METHODS: A cross-sectional study was conducted in Lyon, located at a latitude 45
      N. We included women aged 18 to 49 years, who wore concealing clothes, and
      consulted their GP from November 2005 through March 2006 and had no disease
      likely to cause hypovitaminosis D. Physicians completed a questionnaire and
      collected serum for a vitamin 25 (OH)D assay. We looked for correlations between
      vitamin D deficiency and several factor: ages, parity, associated diseases, and
      clinical signs. RESULTS: The study included 96 women. Defining hypovitaminosis D
      at a threshold of 53 nmol/L or 75 nmol/L, we found a prevalence of 99%, and 72.6%
      of the women had symptoms. Using a stricter threshold of 30 nmol/L, below which
      secondary hyperparathyroidism can appear and reduce bone mass, we found a
      prevalence of 82.5%, 71% of whom were symptomatic. The failure to prescribe
      vitamin D supplementation during the previous 3 months for 99% of these women
      indicates that GPs are not aware of this issue. CONCLUSION: These results
      highlight the endemic character of vitamin D deficiency in a population of young
      women of childbearing age, usually in good health. GPs must be involved in
      targeted activities to screen for and prevent vitamin D deficiency among this
      population, because food sources provide minimal quantities of vitamin D.

PMID- 18061394
TI  - [Respiratory syncytial virus in hospitalized children. A 3-year study].
AB  - OBJECTIVE: To assess the prevalence of respiratory syncytial virus (RSV) and
      other important respiratory viruses in children hospitalized in a pediatric
      hospital in Paris (France) during a 3-year period (2001 to 2004). PATIENTS AND
      METHODS: The study included all patients aged 8 days to 16 years admitted from
      the community through emergency department with bronchiolitis, pneumonia, upper
      respiratory tract infection, asthma or acute isolated fever and who had
      nasopharyngeal samples taken for viral identification by immunofluorescence (RSV,
      influenza, para-influenza, and adenoviruses). RESULTS: A virus was found in 464
      of 1208 patients with samples taken. RSV was identified in 375 patients, 74% of
      them younger than 6 months and diagnosed with bronchiolitis. RSV was isolated
      more often than any other virus, overall and for all diagnoses except "isolated
      fever," for which influenza was more frequent. In patients aged 24 months or
      older, influenza and RSV were identified at the same frequency. Overall,
      influenza virus was found in 53 patients, adenoviruses in 24 and para-influenza
      viruses in 11. CONCLUSION: RSV was the respiratory virus isolated most often,
      even in older children, during this 3-year study. The relative rarity of
      hospitalizations due to para-influenza viruses is characteristic of this area,
      compared with some other countries.

PMID- 18061395
TI  - Onset of streptococcal toxic shock syndrome is accelerated by bruising in a mouse
      model.
AB  - Streptococcal toxic shock syndrome (STSS) is the severest form of human
      infections caused by Streptococcus pyogenes. In our animal model of STSS [Saito
      M, Kajiwara H, Ishikawa T, et al. Delayed onset of systemic bacterial
      dissemination and subsequent death in mice injected intramuscularly with
      Streptococcus pyogenes. Microbiol Immunol 2001;45:777-86], mice inoculated
      intramuscularly with S. pyogenes strains initially suffer from a short illness,
      then recover and remain healthy for about 20 days, and finally become sick and
      incur a sudden death. Here we report that the death during the convalescent
      period was facilitated by artificially bruising an extremity remote from the site
      of the initial inoculation. Bacterial burden was found to be higher in the
      bruised site than in a non-bruised control extremity of each mouse examined.
      Bacteremia started to occur approximately 20 days after infection. These findings
      imply that a fresh bruise serves as a focus for bacterial multiplication in the
      presence of bacteremia, thereby facilitating the development of STSS.

PMID- 18061396
TI  - In vitro reactivation of sarin inhibited electric eel acetylcholinesterase by bis
      pyridinium oximes bearing methoxy ether linkages.
AB  - Bis-pyridinium oximes connected by methoxy alkane ether linker were synthesized
      and their in vitro reactivation efficacy was evaluated for sarin inhibited AChE.
      Reactivation efficacy of synthesized compounds was compared with 2-PAM and
      obidoxime. Among the synthesized compounds, 1,2-dimethoxy ethylene bis-[3,3'
      (hydroxyiminomethyl) pyridinium] dichloride (3P-2) and 1,3-dimethoxy propylene
      bis-[3,3'-(hydroxyiminomethyl) pyridinium] dichloride (3P-3) were found to be
      most potent reactivators for AChE inhibited by nerve agent sarin. 3P-2 and 3P-3,
      respectively exhibited 80% and 69% regeneration of inhibited AChE, whereas 2-PAM
      (well known antidote for nerve agent poisoning) showed 42% regeneration.

PMID- 18061397
TI  - Gene expression profiling in Caco-2 human colon cells exposed to TCDD,
      benzo[a]pyrene, and natural Ah receptor agonists from cruciferous vegetables and
      citrus fruits.
AB  - Cruciferous vegetables and citrus fruits are reported to possess health
      beneficial properties, but also have been shown to contain natural aryl
      hydrocarbon receptor (AhR) agonists (NAhRAs). Binding to the AhR is widely
      assumed to activate the main pathway by which dioxins, like 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) exert their toxicity. To establish whether or
      not activation of the AhR pathway by NAhRAs and dioxin-like substances results in
      similar cellular responses, gene expression profiles induced in Caco-2 cells were
      studied using microarray analysis. Cells were exposed to indolo[3,2-b]carbazole
      (ICZ), an acid reaction product from cruciferous vegetables, and to extracts of
      citrus pulp and grapefruit juice. Gene expression profiles induced by these
      NAhRAs were compared to those of the xenobiotic AhR agonists TCDD and
      benzo[a]pyrene (B[a]P). Over 20 genes were found more than 1.5 times up- or down
      regulated by TCDD, and the expression of most of these genes was modulated in the
      same direction and to a similar extent by B[a]P and the NAhRAs. Results were
      confirmed by RT-PCR, and many of these genes may be involved in dioxin-related
      toxic effects. In conclusion, this in vitro study showed similar effects induced
      by NAhRAs, TCDD and B[a]P at the transcriptome level in a human intestinal cell
      line.

PMID- 18061398
TI  - Expression profiling of signature gene sets with trinucleotide threading.
AB  - In recent years, studies have shown that expression profiling of carefully chosen
      intermediary gene sets, comprising approximately 10 to 100 genes, can convey the
      most relevant information compared to much more complex whole-genome studies. In
      this paper, we present a novel method suitable for expression profiling of
      moderate gene sets in a large number of samples. The assay implements the
      parallel amplification features of the trinucleotide threading technique (TnT),
      which encompasses linear transcript-based DNA thread formation in conjunction
      with exponential multiplexed thread amplification. The amplifications bestow the
      method with high sensitivity. The TnT procedure together with thread detection,
      relying on thread-specific primer extension followed by hybridization to
      universal tag arrays, allows for three distinction levels, thus offering high
      specificity. Additionally, the assay is easily automated and flexible. A gene
      set, comprising 18 protein epitope signature tags from the Swedish Human Protein
      Atlas program, was analyzed with the TnT-based approach and the data were
      compared with those generated by both real-time PCR and genome-wide cDNA arrays,
      with the highest correlation observed between TnT and real-time PCR. Taken
      together, expression profiling with trinucleotide threading represents a reliable
      approach for studies of intermediary gene sets.

PMID- 18061399
TI  - Tac1 regulation by RNA-binding protein and miRNA in bone marrow stroma:
      Implication for hematopoietic activity.
AB  - Hematopoiesis is the process by which immune and blood cells are produced from a
      finite number of relatively few hematopoietic stem cells (HSCs). In adults,
      hematopoiesis occurs in the adult bone marrow (BM), with the support of stromal
      cells. This support partly occurs through the production of hematopoietic
      regulators belonging to the families of cytokines and
      neuropeptides/neurotransmitters, which mediate their actions through specific
      receptors. Thus, stromal cells could be central to the neural-hematopoietic
      immune axis. This study focuses on Tac1, which encodes hematopoietic regulators
      belonging to the tachykinin family of neuropeptides. We examined post
      transcriptional regulation of Tac1 in BM stroma. Since this gene is inducible in
      stroma, we selected cytokines with varying hematopoietic effects: stimulator Stem
      Cell Factor (SCF), broad-acting IL-11 and suppressive TGF-beta1. RNA shift with
      Tac1 mRNA and cytoplasmic extracts from IL-11 and SCF-stimulated stroma showed
      RNA shift after 15min at 37 degrees C, whereas a shift was detected with extracts
      from TGF-beta1-stimulated stroma after 5min at room temperature. Another level of
      post-transcriptional regulation was observed by the detection of miRNAs that
      interact with the 3' untranslated region of Tac1 mRNA. In summary, this study
      showed that cytokine induced miRNA downregulation and RNA-binding protein(s) are
      involved in post-transcriptional regulation of Tac1 in BM stroma. The broad
      categories of cytokines as hematopoietic stimulators or inhibitors might depend
      on the avidity of RNA-binding protein(s) for Tac1 mRNA, as well as the ability to
      degrade or stabilize the specific miRNAs.

PMID- 18061400
TI  - Relations between different coping strategies for social stress, tumor
      development and neuroendocrine and immune activity in male mice.
AB  - This study analyzes the effects of acute social stress and different coping
      strategies employed in response to it on the development of B16F10 melanoma
      pulmonary metastases, the activation of the HPA axis and the NKG2D receptor
      expression. To this end, male OF1 mice were subjected to 24h of social stress
      using the sensorial contact model. This model includes three 5-min sessions of
      direct social interaction with resident cagemates selected for consistent levels
      of aggression. Subjects' behavior was videotaped and assessed. Six days after the
      first social interaction (1st social stress), the animals were inoculated with
      tumor cells or vehicle, and six days later, both tumor-bearing and non tumor
      bearing mice were subjected to a second 24h sensorial contact social stress
      session (2nd social stress). One hour after the 2nd social interaction,
      corticosterone levels and NKG2D receptor expression were determined. Lung
      metastatic foci numbers were determined 21 days after inoculation (15 days post
      stress). Social stress increased the number of pulmonary metastases and the serum
      corticosterone level. A combination of cluster and discriminant analyses
      established the existence of two types of coping strategies: (1) a passive
      reactive strategy characterized by subjects dedicating a greater percentage of
      time to submission, flee and avoidance behaviors; and (2) an active-proactive
      strategy, characterized by subjects dedicating a greater percentage of time to
      attack and non social exploration behaviors. Subjects belonging to the passive
      reactive group were found to have a higher number of tumor foci, a higher level
      of corticosterone and a lower NKG2D receptor expression than subjects in the
      active-proactive group. These data indicate the relationship between different
      coping strategies for social stress and tumor development.

PMID- 18061401
TI  - Postweaning social isolation enhances morphological changes in the neonatal
      ventral hippocampal lesion rat model of psychosis.
AB  - Neonatal ventral hippocampal (nVH) lesions in rats have been widely used as a
      neurodevelopmental model that mimics schizophrenia-like behaviors. Recently, we
      reported that nVH-lesions result in significant decreases in both length of
      dendrites and dendritic density of spines of pyramidal neurons of the prefrontal
      cortex (PFC) and in the density of dendritic spines of medium spiny neurons of
      the nucleus accumbens (NAcc). Moreover, postweaning social isolation induces
      major decreases in dendritic spiny density of PFC neurons. We investigated here
      the comparative dendritic morphology of PFC pyramidal neurons and NAcc medium
      spiny neurons in nVH rats, following social isolation after weaning (8 weeks).
      Morphological characteristics of dendrites were measured using the Golgi-Cox
      procedure followed by a Sholl analysis. Social isolation (SI) by itself induced
      decreases in dendritic length and dendritic spine density of the NAcc. In
      socially isolated nVH-lesion rats decrease in dendritic length in PFC and NAcc
      neurons were exacerbated whereas an increase in spine density of medium spiny
      neurons was observed in the NAcc. These results indicate that nVH-lesions alter
      dendritic morphology of NAcc and PFC neurons. These anatomical modifications in
      both structures may be relevant to behaviors observed in schizophrenia.

PMID- 18061402
TI  - Real-time stereographic rendering and display of medical images with programmable
      GPUs.
AB  - The study was to explore the power and feasibility of using programmable graphics
      processing units (GPUs) for real-time rendering and displaying large 3D medical
      datasets for stereoscopic display workstation. Lung cancer screening CT images
      were used for developing GPU-based stereo rendering and displaying. The study was
      run on a personal computer with a 128 MB NVIDIA Quadro FX 1100 graphics card. The
      performance of rendering and displaying was measured and compared between GPU
      based and central processing unit (CPU)-based programming. The results indicate
      that GPU-based programming was capable of rendering large 3D datasets at real
      time interactive rates with stereographic displays.

PMID- 18061403
TI  - Compartmentalized cAMP signalling in regulated exocytic processes in non-neuronal
      cells.
AB  - Cyclic adenosine monophosphate (cAMP) is a central second messenger controlling a
      plethora of vital functions. Studies of cAMP dynamics in living cells have
      revealed markedly inhomogeneous concentrations of the second messenger in
      different compartments. Moreover, cAMP effectors such as cAMP-dependent protein
      kinase (PKA) and cAMP-activated GTP-exchange factors (Epacs) are tethered to
      specific cellular sites. Both the tailoring of cAMP concentrations, and the
      activities of cAMP-dependent signalling systems at specific cellular locations
      are prerequisites for most, if not all, cAMP-dependent processes. This review
      focuses on the role of compartmentalized cAMP signalling in exocytic processes in
      non-neuronal cells. Particularly, the insertion of aquaporin-2 into the plasma
      membrane of renal principal cells as an example for a cAMP-dependent exocytic
      process in a non-secretory cell type, renin secretion from juxtaglomerular cells
      as a cAMP-triggered exocytosis from an endocrine cell, insulin release from
      pancreatic beta-cells as a Ca2+-mediated and cAMP-potentiated exocytic processes
      in an endocrine cell, and cAMP- or Ca2+ -triggered H+ secretion from gastric
      parietal cells as an exocytic process in an exocrine cell are discussed. The
      selected examples of cAMP-regulated exocytic pathways are reviewed with regard to
      key proteins involved: adenylyl cyclases, phosphodiesterases, PKA, A kinase
      anchoring proteins (AKAPs) and Epacs.

PMID- 18061404
TI  - Dietary intake of folate, other B vitamins, and omega-3 polyunsaturated fatty
      acids in relation to depressive symptoms in Japanese adults.
AB  - OBJECTIVE: Although a favorable effect of dietary folate and omega-3
      polyunsaturated fatty acids (PUFAs) on depression is suggested from epidemiologic
      studies in Western countries, evidence from non-Western populations is lacking.
      We examined cross-sectional associations between the intake of folate, other B
      vitamins, and omega-3 PUFAs and depressive symptoms in Japanese adults. METHODS:
      Subjects were 309 Japanese men and 208 Japanese women 21-67 y of age. Dietary
      intake was assessed with a validated, brief, self-administered diet history
      questionnaire. Depressive symptoms were defined as present when subjects had a
      Center for Epidemiologic Studies Depression scale score > or =16. Adjustment was
      made for age, body mass index, work place, marital status, occupational physical
      activity, leisure-time physical activity, current smoking, current alcohol
      drinking, and job stress score. RESULTS: The prevalences of depressive symptoms
      were 36% for men and 37% for women. Folate intake showed a statistically
      significant, inverse, and linear association with depressive symptoms in men but
      not in women. The multivariate odds ratios (95% confidence intervals) for
      depressive symptoms for men in the first, second, third, and fourth quartiles of
      folate intake were 1.00 (reference), 0.78 (0.38-1.63), 0.57 (0.27-1.18), and 0.50
      (0.23-1.06), respectively (P for trend = 0.045). No statistically significant
      linear association was observed for the intake of riboflavin, pyridoxine,
      cobalamin, total omega-3 PUFAs, alpha-linolenic acid, eicosapentaenoic acid, or
      docosahexaenoic acid in either sex. CONCLUSION: Higher dietary intake of folate
      was associated with a lower prevalence of depressive symptoms in Japanese men but
      not women.

PMID- 18061405
TI  - Differences in nutritional care in pressure ulcer patients whether or not using
      nutritional guidelines.
AB  - OBJECTIVE: Malnutrition, characterized by a loss of lean body mass, enhances the
      risk of pressure ulcers (PUs). Because the intrinsic risk factor nutritional
      status in PU development can be influenced by practitioners' interventions, the
      use of clinical guidelines might be a satisfactory management approach. This
      study investigated the influence of using nutritional guidelines in daily
      practice on the actual nutritional care that PU (prone) patients receive, and
      barriers with regard to providing nutritional support were also explored.
      METHODS: A cross-sectional study was carried out in 1087 hospitals, nursing
      homes, and home care organizations in the Netherlands, Germany, and the United
      Kingdom. Because this study focused on comparing nutritional care in daily
      practice in PU (prone) patients using and not using nutritional guidelines, for
      the analyses two groups (health care organizations with and without guidelines)
      were identified. Differences between groups were tested using chi-square test and
      by analysis of variance. RESULTS: Respondents from 363 organizations participated
      in the study, of which 66.1% used nutritional guidelines for PU care in practice.
      Significant differences between organizations with nutritional guidelines versus
      organizations without guidelines were mostly on nutritional screening (P = 0.001)
      and the extent of nutritional assessments that included significantly more weight
      history recalls, weight measurements, and body mass index measurements (all P <
      0.05). The most important barrier to providing nutritional support for PU (prone)
      patients in both groups was knowledge and skills. CONCLUSION: Using a nutritional
      guideline in PU care contributes to the amount of nutritional screening conducted
      in daily practice and to the content and extent of the assessment.

PMID- 18061406
TI  - Does prenatal methamphetamine exposure affect seizure susceptibility in adult
      rats with acute administration of the same drug?
AB  - The aim of the present study was to investigate whether sensitivity to flurothyl
      seizures after an acute methamphetamine (MA) administration is different in
      prenatally MA-exposed adult rats than in controls without prenatal drug exposure.
      Adult male and female rats exposed prenatally to MA (5mg/kg), saline or neither
      (controls) were divided into groups; one group received acute MA (1mg/kg s.c.)
      injection and the other group received saline. Rats were then challenged with
      flurothyl at a constant flow rate to induce seizures. The threshold of the first
      focal clonus, clonic seizures and tonic-clonic seizures were analyzed. EFFECTS OF
      PRENATAL DRUG EXPOSURE: In animals without acute MA administration prior to
      seizure testing, prenatal MA exposure decreased threshold of the first clonus
      relative to control animals. This decrease in threshold was not apparent in
      groups pretreated with acute MA injection. EFFECTS OF ACUTE MA ADMINISTRATION:
      There was an increased threshold to both, first focal clonus and clonic seizures
      in animals with acute MA injection than in animals without it. The increase
      induced by acute MA pretreatment was higher in prenatally MA-exposed animals
      relative to controls. Further, clonic seizures were shorter and developed faster
      into tonic-clonic seizures in these acutely injected animals compared to animals
      without acute MA injection. EFFECTS OF HORMONES: The threshold of all measured
      attributes was decreased in males. Estrous cycle influences did not lead to
      changes between groups of prenatal exposure or acute MA administration. Threshold
      of tonic-clonic seizures was increased in females in proestrus/estrus stage of
      the estrous cycle relative to diestrous females. Our study suggests that prenatal
      MA exposure affects the sensitivity of adult rats to the effect of acute MA
      treatment prior to flurothyl seizures relative to controls.

PMID- 18061408
TI  - Electron paramagnetic resonance (EPR) spectroscopy for investigating murine
      telogen skin after spontaneous or depilation-induced hair growth.
AB  - BACKGROUND: Depilation has greatly promoted our understanding of hair follicle
      biology, however, only marginally of telogen (the "resting" stage of the hair
      cycle). Since electron paramagnetic resonance (EPR) spectroscopy provides an
      instructive technique for analyzing hair biology, it may be useful for telogen
      research. OBJECTIVES: To identify differences in murine telogen skin after a
      spontaneous and depilation-induced hair follicle cycling, and to analyze
      applicability of EPR to investigate telogen. METHODS: Spontaneous or depilation
      induced hair cycling in C57BL/6 mice. EPR spectroscopy of unshaven skin and of
      shaved hair shafts, microscopical examination of plucked or shed hair shafts,
      standardized histomorphometry. RESULTS: Melanin EPR signals did not differ
      qualitatively between the two examined types of skin, nor did depilation change
      the hair length. However, unmanipulated telogen skin revealed greater thickness,
      stronger EPR signals, 25% more hair shafts, and lower melanin content of
      individual hair shafts, as creating a much more intricate mosaic of telogen hair
      follicles with various numbers of hair shafts (0-3) than the skin after
      depilation-induced hair growth. In both types of skin empty pilary canals were
      found. Both groups of animals lost hair shafts which were typical of exogen (the
      actively controlled process of hair shedding). CONCLUSIONS: EPR spectroscopy can
      be profitably employed to study telogen. Murine telogen skin reveals a kenogen
      like phenomenon (the "lag" phase following telogen and exogen when hair follicles
      remain empty, i.e. are devoid of hair shafts). Murine skin thickness in telogen
      and individual hair shaft pigmentation depend on the way of hair growth
      induction. Telogens after a spontaneous or depilation-induced hair growth are
      biologically distinct.

PMID- 18061407
TI  - The psychological effect of an urban environment on individuals with persecutory
      delusions: the Camberwell walk study.
AB  - BACKGROUND: Epidemiological studies have found that individuals who live in urban
      areas are at increased risk of developing psychosis. However it is unknown
      whether exposure to urban environments exacerbates psychotic symptoms in people
      who have a diagnosed psychotic disorder. The aim of the study was to examine the
      psychological and clinical effects of exposure to one specific deprived urban
      environment on individuals with persecutory delusions. It was predicted that the
      urban environment would affect emotional and reasoning processes highlighted in a
      cognitive model of persecutory delusions and would increase paranoia. METHOD:
      Thirty patients with persecutory delusions were randomised to exposure to a
      deprived urban environment or to a brief mindfulness relaxation task. After
      exposure, assessments of symptoms, reasoning, and affective processes were taken.
      Thirty matched non-clinical participants also completed the study measures to
      enable interpretation of the test scores. RESULTS: In individuals with
      persecutory delusions, exposure to the urban environment, rather than
      participation in a mindfulness task, increased levels of anxiety, negative
      beliefs about others and jumping to conclusions. It also increased paranoia. The
      individuals with persecutory delusions scored significantly differently from the
      non-clinical group on all measures. CONCLUSIONS: For individuals with psychosis,
      spending time in an urban environment makes them think more negatively about
      other people and increases anxiety and the jumping to conclusions reasoning bias.
      Their paranoia is also increased. A number of processes hypothesised in cognitive
      models to lead to paranoid thoughts are exacerbated by a deprived urban
      environment. Further research is needed to clarify which aspects of urban
      environments cause the negative effects. Methodological challenges in the
      research area are raised.

PMID- 18061409
TI  - Reference gene selection for real-time rtPCR in human epidermal keratinocytes.
AB  - BACKGROUND: RNA interference represents a powerful tool with which to achieve
      suppression of specific target mRNA. Real-time rtPCR is a useful technique for
      assessing levels of mRNA expression. Critically, for real-time rtPCR to yield
      meaningful results, it is necessary to normalise expression of the gene of
      interest to stably expressed endogenous control genes. OBJECTIVES: The study
      involved establishing expression profiles for 11 housekeeping genes in human
      epidermal keratinocyte cell lines determining their relative stability.
      Furthermore, the effect of the presence of shRNA on these expression profiles has
      been established. METHODS: Keratinocytes were transfected using lipid-based
      transfection or AMAXA nucleofection. Real-time rtPCR was used to establish RNA
      expression levels. Data analysis was carried out using geNORM. RESULTS: When
      using HaCaT or adult NHEK cells any combination of 8 of the housekeeping genes
      would be appropriate for normalisation. In contrast, with juvenile NHEK cells
      only 4 of the housekeeping genes were found to be sufficiently stable to be
      deemed appropriate for normalisation of expression data. Furthermore data
      demonstrated that the expression of housekeeping genes may sometimes be affected
      by the induction of the RNAi pathway. CONCLUSIONS: The data obtained highlight
      the importance of characterising housekeeping gene expression profiles in each
      specific cell type prior to choosing a set of housekeeping genes for expression
      studies. The results from this study are applicable to researchers working with
      human epidermal keratinocytes and the experimental approach is more broadly
      applicable to any researcher carrying out real-time rtPCR.

PMID- 18061410
TI  - Meropenem-aggravated seizure activity in progressive myoclonus epilepsy.

PMID- 18061411
TI  - Antimicrobial susceptibility profiles of 32 type strains of Lactobacillus,
      Bifidobacterium, Lactococcus and Streptococcus spp.

PMID- 18061412
TI  - Repeated treatment with haloperidol, but not olanzapine, alters synaptic NMDA
      receptor composition in rat striatum.
AB  - We here show that repeated administration of the first generation antipsychotic
      haloperidol, but not of the second generation olanzapine, significantly reduced
      the expression of NMDA subunit NR2A at striatal synapses, whereas both drugs
      decreased alphaCaMKII protein levels and autophosphorylation degree. Given that
      alterations in the localization of NMDA receptor regulatory subunits at synapses
      have been described in experimental parkinsonism, the haloperidol-induced effect
      on NMDA subunit localization might contribute to drug-induced parkinsonism
      induced by haloperidol.

PMID- 18061413
TI  - 'Bleedin' difficult'--chronic radiation proctitis.

PMID- 18061414
TI  - Neuroendocrine control of food intake.
AB  - Appetite is regulated by a complex system of central and peripheral signals which
      interact in order to modulate the individual response to nutrient ingestion.
      Peripheral regulation includes satiety signals and adiposity signals, while
      central control is accomplished by several effectors, including the
      neuropeptidergic, monoaminergic and endocannabinoid systems. Satiety signals,
      including cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide YY
      (PYY), originate from the gastrointestinal (GI) tract during a meal and, through
      the vagus nerve, reach the nucleus tractus solitarius (NTS) in the caudal
      brainstem. From NTS afferents fibers project to the arcuate nucleus (ARC), where
      satiety signals are integrated with adiposity signals, namely leptin and insulin,
      and with several hypothalamic and supra-hypothalamic inputs, thus creating a
      complex network of neural circuits which finally elaborate the individual
      response to a meal. As for the neuropeptidergic system, ARC neurons secrete
      orexigenic substances, such as neuropeptide Y (NPY) and agouti-related peptide
      (AGRP), and anorexigenic peptides such as pro-opiomelanocortin (POMC) and cocaine
      and amphetamine-regulated transcript (CART). Other brain areas involved in the
      control of food intake are located downstream the ARC: among these, the
      paraventricular nucleus (PVN), which produces anorexigenic peptides such as
      thyrotropin releasing hormone (TRH), corticotrophin releasing hormone (CRH) and
      oxytocin, the lateral hypothalamus (LHA) and perifornical area (PFA), secreting
      the orexigenic substances orexin-A (OXA) and melanin concentrating hormone (MCH).
      A great interest in endocannabinoids, important players in the regulation of food
      intake, has recently developed. In conclusion, the present work reviews the most
      recent insights into the complex and redundant molecular mechanisms regulating
      food intake, focusing on the most encouraging perspectives for the treatment of
      obesity.

PMID- 18061416
TI  - Moderate alcohol consumption and lipoprotein-associated phospholipase A2
      activity.
AB  - BACKGROUND AND AIMS: To investigate the effect of moderate alcohol consumption on
      lipoprotein-associated phospholipase A2 activity, markers of inflammation and
      oxidative stress and whether these effects are modified by BMI. METHODS AND
      RESULTS: Eleven lean (BMI: 18.5-25 kg/m(2)) and 9 overweight (BMI>27 kg/m(2)) men
      participated in a randomized controlled crossover trial. After consuming 3 cans
      of beer (40 g ethanol) or alcohol-free beer daily during 3 weeks, fasting blood
      samples were taken. HDL cholesterol increased by 18.2% (p<0.001) after beer
      compared to alcohol-free beer, while LDL cholesterol decreased by 7.8% (p=0.008).
      Lipoprotein-associated phospholipase A2 activity was not different (p=0.23)
      between beer (47.5+/-0.8) and alcohol-free beer (48.9+/-0.8). High-sensitive C
      reactive protein was unaffected, but urinary isoprostanes tended to increase
      (p=0.09) after beer (114.0+/-6.9) compared to alcohol-free beer (96.9+/-6.5). An
      interaction between BMI and treatment (p<0.05) on liver enzymes was observed,
      indicating an increase of liver enzymes after moderate alcohol consumption in
      overweight men only. CONCLUSION: Despite profound effects on HDL and LDL
      cholesterol, moderate alcohol consumption did not affect lipoprotein-associated
      phospholipase A2 activity. Liver enzymes increased after alcohol consumption in
      overweight men only, suggesting a less favorable response to moderate alcohol
      consumption in overweight people.

PMID- 18061415
TI  - The Italian Diabetes and Exercise Study (IDES): design and methods for a
      prospective Italian multicentre trial of intensive lifestyle intervention in
      people with type 2 diabetes and the metabolic syndrome.
AB  - BACKGROUND AND AIMS: The IDES is a prospective Italian multicentre randomized
      controlled trial to evaluate the efficacy of an intensive lifestyle intervention
      on modifiable cardiovascular disease (CVD) risk factors in a large cohort of
      people with type 2 diabetes and the metabolic syndrome. METHODS AND RESULTS: We
      recruited 606 subjects with type 2 diabetes and waist circumference >94 cm (M)
      and >80 cm (F), plus >1 other metabolic syndrome trait (IDF criteria) for both
      sexes, aged 40-75 years, BMI 27-40 kg/m(2), diabetes duration >1 year with a
      sedentary lifestyle of >6 months. Patients were randomized into two groups: a
      control group, receiving conventional care including exercise counselling and an
      intervention group, treated with a mixed (aerobic and resistance) exercise
      programme (150 min/week) prescribed and supervised for 12 months. Primary outcome
      is HbA1c reduction. Secondary outcomes include other traditional and non
      traditional risk factors and their relationship to exercise volume/intensity and
      fitness; dosage of glucose, lipid and blood pressure-lowering drugs; global CVD
      10-year risk; patient well-being; and costs. CONCLUSION: This trial verifies
      whether a prescribed and supervised exercise programme, including both aerobic
      and resistance training, is more effective than conventional exercise counselling
      in reducing modifiable CVD risk factors in type 2 diabetic subjects with the
      metabolic syndrome.

PMID- 18061417
TI  - Effects of Microdesmis keayana roots on sexual behavior of male rats.
AB  - In the present study, the aphrodisiac properties of Microdesmis keayana J.
      Leonard root extract and major isolated alkaloids were evaluated by observing the
      sexual behavior of male rats. Aqueous extract (150mg/kg body weight) and pure
      alkaloids (3mg/kg body weight) were administered orally by gavage to male rats.
      Latent times of observation, intromission and ejaculation, mounting behavior,
      number of intromissions and mating performances were evaluated and compared to
      those obtained with untreated rats in the presence of receptive and non-receptive
      females. The results have shown that aqueous extract and alkaloids of M. keayana
      stimulate sexual parameters in rats' sexual behavior. A short-term toxicity study
      undertaken to establish the therapeutic index of aqueous extract, showed that a
      high dose of the extract (2g/kg body weight) caused no mortality or changes in
      rats' behavior.

PMID- 18061418
TI  - Antiproliferative activity of triterpenoids from Eclipta prostrata on hepatic
      stellate cells.
AB  - Hepatic stellate cells (HSCs) have been known to play a key role in the
      pathogenesis of liver fibrosis. In the course of screening antifibrotic activity
      of natural products employing HSC-T6, a rat hepatic stellate cell line as an in
      vitro assay system, the methanolic extract of aerial parts of Eclipta prostrata
      L. showed significant inhibitory activity on HSCs proliferation. Activity-guided
      fractionation led to the isolation of five oleanane-type triterpenoids,
      echinocystic acid (1), eclalbasaponin II (2), eclalbasaponin V (3),
      eclalbasaponin I (4) and eclalbasaponin III (5), which are all echinocystic acid
      derivatives. Among the five echinocystic acid derivatives isolated, echinocystic
      acid (1) and eclalbasaponin II (2) significantly inhibited the proliferation of
      HSCs in dose- and time-dependent manners. Our present study also suggests the
      importance of free carboxylic acid at C-28 position in echinocystic acid
      derivatives for the antifibrotic activity. Taken together, antifibrotic activity
      of E. prostrata and its triterpenoids might suggest the therapeutic potentials
      against liver fibrosis.

PMID- 18061419
TI  - Src kinase regulates metalloproteinase-9 secretion induced by type IV collagen in
      MCF-7 human breast cancer cells.
AB  - Matrix metalloproteinases (MMPs) are a family of endopeptidases that collectively
      are capable to degrading all components of the extracellular matrix (ECM) and
      they have been implicated in several aspects of tumor progression, such as
      invasion through basement membrane (BM) and insterstitial matrices, angiogenesis
      and tumor cell growth. In particular, MMP-2 and MMP-9 have been associated with
      the ability of tumor cells to metastasize due to their capacity to degrade type
      IV collagen (Col-IV), the main component of BM, and to their elevated expression
      in malignant tumors. However, nothing is known about the regulation of MMP-9
      secretion and expression in breast cancer cells stimulated with Col-IV. Our
      results demonstrate that stimulation of MCF-7 cells with Col-IV promoted the
      secretion of MMP-9, as revealed by gelatin zymography and Western blotting using
      specific antibodies that recognized MMP-9. In addition, inhibition of Src and FAK
      kinase activity prevented MMP-9 secretion. In contrast, MMP-9 expression was not
      up-regulated by treatment with Col-IV. These results demonstrate that Col-IV
      regulates the secretion of MMP-9 via a Src and FAK dependent pathway in MCF-7
      cells.

PMID- 18061420
TI  - Methods used in clinical development of novel anti-asthma therapies.
AB  - In recent years, it has become increasingly important to get as much as possible
      information on clinical efficacy already in the early phases of drug development.
      For proof of concept (POC) studies testing novel anti-inflammatory drugs in
      asthma, there are several validated exacerbation models, inducing various aspects
      of the airway inflammation and airway responsiveness. The choice of the
      appropriate asthma model depends on the drug's targets within the inflammatory
      process. For adequate assessment of the drug's anti-inflammatory potential, it is
      crucial to choose adequate (surrogate) biomarkers. Ideally, these should include
      measures of airway response, central and peripheral airway inflammation and
      airway hyperresponsiveness. Overall, there are validated non-invasive sampling
      techniques for the measurement of inflammatory markers in asthma that can be
      applied as outcome parameters in early clinical trials. If adequately
      implemented, these measurements can provide early indication of proof of
      pharmacological and potential therapeutic efficacy-even in first administration
      to humans.

PMID- 18061421
TI  - Perceived triggers of asthma: evaluation of a German version of the Asthma
      Trigger Inventory.
AB  - BACKGROUND AND OBJECTIVE: Patients' perception of asthma triggers has been
      explored in a largely unstructured fashion in the past. Therefore, we developed
      the Asthma Trigger Inventory (ATI), a questionnaire that allows for a
      psychometrically valid measurement of patients' perceived asthma triggers. Here
      we evaluate a German language version of the ATI and studied the relationship of
      subscales with self-reported health status, health care use, psychopathology, and
      results of allergy skin testing. METHOD: Data were obtained from 370 asthma
      patients recruited from the community, primary care, and in-patient asthma
      treatment and education. RESULTS: Analysis revealed a five-factor structure that
      largely confirmed results with the English original. Reliability was good to
      satisfactory (Cronbach's alpha=0.77-0.89) for allergy, exercise, air
      pollution/irritants, infection, and psychological trigger subscales. In
      hierarchical regression analysis adjusting for demographics and asthma severity,
      asthma patients with stronger non-allergic triggers showed less physical and
      mental well-being and more asthma-related health care use. Psychological triggers
      showed unique associations with anxious and depressed mood. Pollen and animal
      allergen scores of the ATI were significantly related to skin test results for
      relevant allergens. Non-allergic but not allergic triggers showed substantial
      associations with asthma control. CONCLUSION: The German version of the ATI
      reliably measures asthma patients' trigger perceptions. Non-specific asthma
      triggers exert a greater burden on patients' well-being and primary health care
      use.

PMID- 18061422
TI  - Respiratory symptoms, COPD severity, and health related quality of life in a
      general population sample.
AB  - AIMS: The aim of this report from a general population sample was to examine the
      association of respiratory symptoms and COPD severity with HRQoL (health related
      quality of life). METHODS: In a general population study in 1996-1997, of 3181
      invited subjects aged 26-81 years, a total of 2405 returned postal questionnaires
      on respiratory symptoms and attended a clinical examination. Altogether 2306
      subjects completed the SF-12 questionnaire, a general HRQoL questionnaire. The
      univariate relationships between respiratory symptom burden, degree of bronchial
      obstruction, and HRQoL were investigated by the Wilcoxon test for trend and the
      Mann-Whitney U-test. Adjustment for gender, age, education, and smoking habits
      was done using linear regression with estimation of robust standard errors.
      RESULTS: In asymptomatic subjects the mean (SD) physical component scale (PCS)
      score was 51.8 (7.4) and the mean (SD) mental component scale (MCS) score was
      52.6 (8.0). Having one to six symptoms gave mean (SD) PCS scores of 49.6 (8.8),
      48.2 (9.7), 45.1 (10.4), 42.1 (11.9), 38.1 (11.4), and 34.7 (10.2), respectively.
      The corresponding numbers for MCS scores were 50.9 (8.0), 48.8 (9.6), 48.9
      (10.6), 47.2 (10.2), 43.6 (10.4), and 44.2 (9.8), respectively. In the
      multivariate model, subjects in GOLD stages 3 and 4 had significantly reduced PCS
      scores, while subjects with COPD had a significantly higher MCS score than
      subjects without COPD, after adjustment for symptoms. Both the PCS and MCS scores
      declined significantly with increasing number of respiratory symptoms.
      CONCLUSION: In a general population sample, the burden of respiratory symptoms is
      more strongly associated with generic HRQoL than is lung function.

PMID- 18061423
TI  - Long-term repeatability of exhaled breath condensate pH in asthma.
AB  - Exhaled breath condensate (EBC) is being used increasingly to sample airway
      fluid. EBC pH may be a biomarker of airway inflammation in asthma. In this study,
      we assessed the long-term reproducibility of EBC pH in asthma. We examined 31
      asthmatic patients and eight healthy subjects three times over a 1-year period
      (winter, autumn and summer). EBC pH was measured after argon deaeration.
      Repeatability of pH measurements was assessed using intraclass correlation
      coefficients (ICC) and the limits of agreement (LOA) between seasons were
      calculated according to Bland-Altman method. No significant differences in EBC pH
      between seasons were detected in healthy subjects and asthmatic patients. EBC pH
      showed high repeatability either in healthy subjects (ICC=0.94) or in asthmatics
      (ICC=0.97). Variability between seasons was greater in asthmatics than in healthy
      subjects: winter-autumn LOA -0.68/+0.52 and -0.31/+0.31, autumn-summer LOA 
      0.75/+0.67 and -0.24/+0.15, winter-summer LOA -0.92/+0.67 and -0.34/+0.23 in
      asthmatic and healthy subjects, respectively. In a subgroup of 11 asthmatics who
      remained in stable conditions during the study, no substantially different LOA
      were observed in EBC pH compared with the whole group of asthmatics. Asthmatic
      smokers (n=10) tended to have lower EBC pH (7.57+/-0.46) than asthmatic non
      smokers (n=21) (7.74+/-0.21; p=0.063) and wider LOA. In conclusion, we
      demonstrated that EBC pH exhibits good repeatability in long-term assessment. EBC
      pH in asthmatics tended to fluctuate more than in healthy subjects. However, EBC
      pH variability in asthma was not influenced by changes in clinical status.
      Rather, we suggest that cigarette smoke may be implicated in EBC pH variability.

PMID- 18061424
TI  - Depression and panic disorder as predictors of health outcomes for patients with
      asthma in primary care.
AB  - INTRODUCTION: Depression and panic disorder are widely acknowledged as
      complicating factors in asthma patients. However, their impact on health outcomes
      in primary care patients is less well examined. This study prospectively
      evaluated the impact of depression and panic disorder on outcomes of primary care
      patients with asthma over 1 year. METHODS: At baseline, 256 asthma patients from
      43 primary care practices completed self-report questionnaires including the
      Patient Health Questionnaire (PHQ), the Asthma Quality of Life Questionnaire
      (AQLQ), and a structured questionnaire evaluating asthma severity,
      hospitalisation and emergency visits. One year later, 185 (72.3%) patients
      completed the same questionnaire. RESULTS: At baseline, 3.9% of patients suffered
      from major depressive disorder, 22.7% from minor depressive disorder, and 7.8%
      from panic disorder. In the year under evaluation, 17 patients (9.2%) received
      emergency home visits and 10 patients (5.4%) were admitted to a hospital.
      Depression at baseline predicted hospitalisation within the subsequent year (OR
      6.1; 95% CI 1.5-24.6) and panic disorder predicted unscheduled emergency home
      visits (OR 4.8; 95% CI 1.3-17.7). Depression but not panic disorder predicted the
      AQLQ scales activity (p=0.001), symptoms (p=0.001), emotions (p=0.001) and
      environment (p=0.001) at follow-up. CONCLUSIONS: Although rates of
      hospitalisation and emergency visits in primary care are low, the impact of
      psychiatric comorbidity on health outcomes for patients with asthma is
      substantial. It might be helpful to identify patients with psychiatric
      comorbidity by analysing reasons for hospitalisation and emergency visits. For
      these patients, intensifying care with psychiatric interventions might help to
      reduce inappropriate healthcare utilisation and avoid adverse outcomes.

PMID- 18061425
TI  - The primary cilia, a 'Rab-id' transit system for hedgehog signaling.
AB  - Intense focus has been centered around how the primary cilia transduces the
      hedgehog (Hh) signal from smoothened (Smo) to the Gli transcription factors. New
      data indicate that ligand and signaling lipids help regulate small GTPase
      dependent accumulation and activity of signaling components.

PMID- 18061429
TI  - Longitudinal changes in zinc transport kinetics, metallothionein and zinc
      transporter expression in a blood-brain barrier model in response to a moderately
      excessive zinc environment.
AB  - A blood-brain barrier (BBB) model composed of porcine brain capillary endothelial
      cells (BCEC) was exposed to a moderately excessive zinc environment (50
      micromol/L Zn) in cell culture, and longitudinal measurements were made of zinc
      transport kinetics, ZnT-1 (SLC30A1) expression and changes in the protein
      concentration of metallothionein (MT), ZnT-1, ZnT-2 (SLC30A2) and Zip1 (SLC39A1).
      Zinc release by cells of the BBB model significantly increased after 12-24 h of
      exposure, but decreased back to control levels after 48-96 h, as indicated by
      transport across the BBB from both the ablumenal (brain) and the lumenal (blood)
      directions. Expression of ZnT-1, the zinc export protein, increased by 169%
      within 12 h, but was no longer different from controls after 24 h. Likewise, ZnT
      1 protein content increased transiently after 12 h of exposure, but returned to
      control levels by 24 h. Capacity for zinc uptake and retention increased from
      both the lumenal and the ablumenal directions within 12-24 h of exposure and
      remained elevated. MT and ZnT-2 were elevated within 12 h and remained elevated
      throughout the study. Zip1 was unchanged by the treatment. The BBB's response to
      a moderately high zinc environment was dynamic and involved multiple mechanisms.
      The initial response was to increase the cells' capacity to sequester zinc with
      additional MT and to increase zinc export with the ZnT-1 protein. But the longer
      term strategy involved increasing ZnT-2 transporters, presumably to sequester
      zinc into intracellular vesicles as a mechanism to protect the brain and to
      maintain brain zinc homeostasis.

PMID- 18061427
TI  - Formation and regeneration of the endocrine pancreas.
AB  - The elaboration of the pancreas from epithelial buds to the intricate organ
      requires complex patterning information that controls fundamental cellular
      processes such as differentiation and proliferation of pancreatic progenitor
      cells. During pancreatic organogenesis, endocrine cells are generated from a
      population of pancreatic progenitor cells. The progenitor cells during the early
      development simultaneously receive multiple signals, some mitogenic and some
      inducing differentiation. These extrinsic signals are interpreted through an
      intrinsic mechanism that either commits the progenitor cell to the mitotic cell
      cycle or leads to exit from the cell cycle in order to differentiate. The
      endocrine cells that differentiate from progenitor cells are postmitotic, and
      direct lineage tracing analyses indicate that a population of progenitor cells
      persists throughout embryogenesis to allow the differentiation of new endocrine
      cells. At the end of embryogenesis an early postnatal period is characterized by
      high rates of beta cell proliferation leading to massive increases in beta cell
      mass. The beta cell mass expansion considerably slows down in adult animals,
      though variations in insulin demand due to physiological and pathological states
      such as pregnancy and obesity can lead to adaptive changes in the beta cells that
      include hyperplasia, hypertrophy, and increased insulin synthesis and secretion.
      Deciphering the mechanisms that regulate the plasticity of beta cell mass can be
      an important step in developing effective strategies to treat diabetes.

PMID- 18061430
TI  - Intestinal immune system of young rats influenced by cocoa-enriched diet.
AB  - Gut-associated lymphoid tissue (GALT) maintains mucosal homeostasis by
      counteracting pathogens and inducing a state of nonresponsiveness when it
      receives signals from food antigens and commensal bacteria. We report for the
      first time the influence of continuous cocoa consumption on GALT function in rats
      postweaning. Weaned Wistar rats were fed cocoa-enriched diets (4% or 10% food
      intake) for 3 weeks. The function of the primary inductive sites of GALT, such as
      Peyer's patches (PP) and mesenteric lymph nodes (MLN), was evaluated through an
      analysis of IgA-secretory ability and lymphocyte composition (T, B and natural
      killer cells), activation (IL-2 secretion and IL-2 receptor alpha expression) and
      proliferation. T-helper effector cell balance was also established based on
      cytokine profile (interferon gamma, IL-4 and IL-10) after mitogen activation. A
      10% cocoa intake induced significant changes in PP and MLN lymphocyte composition
      and function, whereas a 4% cocoa diet did not cause significant modifications in
      either tissues. Cocoa diet strongly reduced secretory IgA (S-IgA) in the
      intestinal lumen, although IgA's secretory ability was only slightly decreased in
      PP. In addition, the 10% cocoa diet increased T-cell-antigen receptor gammadelta
      cell proportion in both lymphoid tissues. Thus, cocoa intake modulates intestinal
      immune responses in young rats, influencing gammadelta T-cells and S-IgA
      production.

PMID- 18061432
TI  - Harm reduction coming of age: A summary of the '18th International Conference on
      the Reduction of Drug Related Harm'-Warsaw, Poland: 13-17 May 2007.

PMID- 18061431
TI  - Inhibition of histone-deacetylase activity by short-chain fatty acids and some
      polyphenol metabolites formed in the colon.
AB  - Colorectal cancer is the most abundant cause of cancer mortality in the Western
      world. Nutrition and the microbial flora are considered to have a marked
      influence on the risk of colorectal cancer, the formation of butyrate and other
      short-chain fatty acids (SCFAs) possibly playing a major role as chemopreventive
      products of microbial fermentation in the colon. In this study, we investigated
      the effects of butyrate, other SCFAs, and of a number of phenolic SCFA and trans
      cinnamic acid derivatives formed during the intestinal degradation of
      polyphenolic constituents of fruits and vegetables on global histone deacetylase
      (HDAC) activity in nuclear extracts from colon carcinoma cell cultures using tert
      butoxycarbonyl-lysine (acetylated)-4-amino-7-methylcoumarin (Boc-Lys(Ac)-AMC) as
      substrate. Inhibition of HDAC activity, e.g., by butyrate, is related to a
      suppression of malignant transformation and a stimulation of apoptosis of
      precancerous colonic cells. In nuclear extracts from HT-29 human colon carcinoma
      cells, butyrate was found to be the most potent HDAC inhibitor (IC50=0.09 mM),
      while other SCFAs such as propionate were less potent. In the same assay, p
      coumaric acid (IC50=0.19 mM), 3-(4-OH-phenyl)-propionate (IC50=0.62 mM) and
      caffeic acid (IC50=0.85 mM) were the most potent HDAC inhibitors among the
      polyphenol metabolites tested. Interestingly, butyrate was also the most potent
      HDAC inhibitor in a whole-cell HeLa Mad 38-based reporter gene assay, while all
      polyphenol metabolites and all other SCFAs tested were much less potent; some
      were completely inactive. The findings suggest that butyrate plays an outstanding
      role as endogenous HDAC inhibitor in the colon, and that other SCFAs and HDAC
      inhibitory polyphenol metabolites present in the colon seem to play a much
      smaller role, probably because of their limited levels, their marked cytotoxicity
      and/or their limited intracellular availability.

PMID- 18061433
TI  - Experimental study on flue gas purifying of MSW incineration using in-pipe jet
      adsorption techniques.
AB  - This paper presents the experimental research process and results about flue gas
      purifying of municipal solid wastes (MSW) incineration using in-pipe jet
      adsorption techniques. MSW incineration was carried out in a fluidized bed test
      rig, and the flue gas purifying was carried out in an in-pipe jet adsorption test
      rig. The experimental results are as follows: when the feedstock of activated
      carbon is 1.6g/Nm(3), the desulfurization efficiency is 83%, the denitrification
      efficiency is 41%, and the dechlorination efficiency is 27%. The order of
      purifying effect of the three kinds of adsorbents on acidic gases from MSW
      incineration is activated carbon>activated bauxite>kaolin. Comparison of
      adsorption capabilities of the three kinds of adsorbents to heavy metals shows
      that activated carbon is the best additive to remove Cd, Pb and Cu, kaolin is
      inferior, and activated bauxite is the worst one. However, activated bauxite is
      the best additive to remove Hg, and it can remove Cd effectively. PAHs in fly ash
      are dominated by three-, four-, and five-ringed PAHs, and PAHs in the flue gas
      mainly include three- and four-ringed PAHs. When the injected quantity of
      additive is constant, the order of cleaning effect on PAHs is kaolin>activated
      carbon>activated bauxite. These three kinds of adsorbents have different
      purifying effects on acidic gases, heavy metals and PAHs in the flue gas from MSW
      incineration. In general, activated carbon has a better adsorption capability.

PMID- 18061434
TI  - Carbon sequestration in European soils through straw incorporation: limitations
      and alternatives.
AB  - We compared alternate uses of cereal straw (4.25t dry matter ha(-1) containing
      1.7t carbon (C)) for their effectiveness in relation to climate change
      mitigation. The scenarios were (1) incorporation into soil to increase soil
      organic carbon (SOC) content ("carbon sequestration") and (2) combustion to
      generate electricity. The Rothamsted Carbon Model was used to estimate SOC
      accumulation in a silty clay loam soil under the climatic conditions of north
      west Europe. Using straw for electricity generation saved seven times more CO2
      than from SOC accumulation. This comparison assumed that electricity from straw
      combustion displaced that generated from coal and used the mean annual
      accumulation of SOC over 100yr. SOC increased most rapidly in the early years,
      but then more slowly as a new equilibrium value was approached. We suggest that
      increased SOC from straw incorporation does not represent genuine climate change
      mitigation through carbon sequestration. In Europe, most straw not already
      incorporated in the field where it is grown is subsequently returned elsewhere,
      e.g., after use for animal bedding and production of manure. Only additional
      retention of C in soil compared to the alternative use represents sequestration.
      Maintenance of SOC for soil functioning is a more appropriate rationale for
      returning straw to soil than climate change mitigation. This analysis shows that
      considerably greater climate change mitigation is achieved through saved CO2
      emissions by burning straw for electricity generation, replacing some use of
      fossil fuel.

PMID- 18061435
TI  - Enhancement of odorant detection sensitivity by the expression of odorant-binding
      protein.
AB  - Odorant-binding proteins are low molecular weight, soluble proteins that are
      secreted by glands of the nasal cavity. Their function is known to be the
      transport of hydrophobic odorants. This feature is important to artificial
      olfactory biosensors, which operate in the aqueous phase. In this study, one of
      rat odorant-binding proteins, OBP3, was inserted into a mammalian expression
      vector pcDNA3, expressed, and secreted from human embryonic kidney-293 (HEK-293)
      cells. The his(6) tag and signal peptide of the prelysozyme (plys) were fused
      with OBP3 for the detection and secretion of the proteins, respectively. The
      secretion level of OBP3 was maximal at 3h of incubation time. The secreted OBP3
      increased the solubility of a hydrophobic odorant, octanal, which is the specific
      odorant of rat olfactory receptor I7. The secreted OBP3 also bound to olfactory
      receptor I7. These interactions consequently increased the cellular signal
      intensity stimulated by the odorant in the cells expressing olfactory receptor
      I7. Our findings indicate that odorant-binding protein can be effectively used to
      increase the sensitivity of olfactory receptor-based biosensors.

PMID- 18061436
TI  - Protective effect from solar exposure, risk of an ecological fallacy.
AB  - Solar exposure, vitamin D, and their possible beneficial effect on cancer risk
      and cancer prognosis are a topic for research. Despite the distinct nature of
      sunlight, it has proved difficult to assess the exposure quantitatively in
      epidemiological studies. Skin cancers, latitude, and sunny climate have been used
      as proxy indicators of solar exposure above a reference level. The interpretation
      of such data may still be hampered by incomplete cancer registration, difference
      in protection against sunbeams, selection mechanisms, and absence of information
      on potential confounders. A recently published paper -- on second primary cancer
      following the diagnosis of a skin cancer -- is discussed to illustrate the
      difficulties. Further epidemiological studies of potentially protective effects
      from carcinogenic ultraviolet rays should include individual information on solar
      exposure and vitamin D levels, as well as on other recognised and relevant risk
      factors.

PMID- 18061437
TI  - Identification of a novel, functional role for S100A13 in invasive lung cancer
      cell lines.
AB  - The S100 family is a group of small, calcium-binding proteins with at least 20
      distinct members in humans. Several of these have been associated with cancer
      invasion or metastasis in recent studies. Transcriptional analysis of gene
      expression in a panel of lung cancer-derived cell lines identified S100A13 as
      being associated with a more aggressive invasive phenotype in vitro. Hierarchical
      clustering grouped this gene with several others that have established functional
      roles in this phenotype both in vitro and in vivo (ICAM1, CD34, EFNB2 and HGF) as
      well as genes involved in processes such as angiogenesis (TEM7, JAG2). Depletion
      of cellular S100A13 mRNA levels by RNAi in highly invasive lung cancer cell lines
      resulted in a 50-80% decrease in their invasive potential in an in vitro assay.
      This reduction could not be accounted for by reduced cellular proliferation.
      Conversely, transient overexpression of exogenous S100A13 in less invasive cell
      lines had no impact on invasive potential suggesting that upregulation of S100A13
      expression alone is insufficient to induce the phenotype. We conclude that
      S100A13 is involved in but not capable of inducing invasion, since elevated
      S100A13 mRNA expression correlates with a more invasive phenotype and in vitro
      invasion can be inhibited by reduced S100A13 expression.

PMID- 18061438
TI  - Novel molecular profiles of endometrial cancer-new light through old windows.
AB  - Endometrial carcinoma (EC) is the most common gynecological malignancy in the
      western world. A widely accepted dualistic model, which has been established on a
      morphological basis, differentiates EC into two broad categories: Type I
      oestrogen-dependent adenocarcinoma with an endometrioid morphology and Type II
      non-oestrogen-dependent EC with a serous papillary or clear cell morphology.
      Molecular genetic evidence indicates that endometrial carcinoma, as described in
      other malignancies, likely develops as the result of a stepwise accumulation of
      alterations in cellular regulatory pathways, such as oncogene activation and
      tumor suppressor gene inactivation, which lead to dysfunctional cell growth.
      These molecular alterations appear to be specific in Type I and Type II cancers.
      In type I endometrioid endometrial cancer, PTEN gene silencing in conjunction
      with defects in DNA mismatch repair genes, as evidenced by the microsatellite
      instability phenotype, or mutations in the K-ras and/or beta-catenin genes, are
      recognized major alterations, which define the progression of the normal
      endometrium to hyperplasia, to endometrial intraepithelial neoplasia, and then on
      to carcinoma. In contrast, Type II cancers show mutations of TP53 and Her-2/neu
      and seem to arise from a background of atrophic endometrium. Nevertheless,
      despite the great effort made to establish a molecularly-based histological
      classification, the following issues must still be clarified: what triggers the
      tumor cells to invade the myometrium and what causes vascular or lymphatic
      dissemination, finally culminating in metastasis? RUNX1, a transcription factor,
      was recently identified as one of the most highly over-expressed genes in a
      microarray study of invasive endometrial carcinoma. Another candidate gene, which
      may be associated with an initial switch to myometrial infiltration, is the
      transcription factor ETV5/ERM. These studies, as well as those conducted for
      other genes possibly involved in the mitotic checkpoint as a major mechanism of
      carcinogenesis in non-endometrioid endometrial cancer, could help in
      understanding the differences in the biology and the clinical outcome among
      histological types.

PMID- 18061439
TI  - Kinetic investigations of methane co-fermentation of sewage sludge and organic
      fraction of municipal solid wastes.
AB  - In the presented study the co-fermentation, fermentation of sewage sludge (SS)
      and fermentation of organic fraction of municipal solid waste (OFMSW) were
      compared. The goal of experiments was determination of the processes carbon
      balance and proposal of the simple kinetic model of anaerobic digestion. Three
      batch experiments with above mentioned feedstocks were conducted in large scale
      laboratory reactor of working volume of 40 dm(3). The cumulative biogas
      production for sewage sludge (180.59 dm(3)) was lower than that for co
      fermentation (232 dm(3)) or OFMSW (228.34 dm(3)). During fermentation of the
      OFMSW an accumulation of volatile fatty acids (VFA) caused pH decrease and
      strongly inhibited gas production. The addition of co-substrate improved
      buffering capacity of fermentation broth. The suggested mathematical descriptions
      of carbon division in anaerobic digestion processes gave the satisfying
      conformity with the experimental values.

PMID- 18061440
TI  - Butanol production by Clostridium beijerinckii. Part I: use of acid and enzyme
      hydrolyzed corn fiber.
AB  - Fermentation of sulfuric acid treated corn fiber hydrolysate (SACFH) inhibited
      cell growth and butanol production (1.7+/-0.2g/L acetone butanol ethanol or ABE)
      by Clostridium beijerinckii BA101. Treatment of SACFH with XAD-4 resin removed
      some of the inhibitors resulting in the production of 9.3+/-0.5 g/L ABE and a
      yield of 0.39+/-0.015. Fermentation of enzyme treated corn fiber hydrolysate
      (ETCFH) did not reveal any cell inhibition and resulted in the production of
      8.6+/-1.0 g/L ABE and used 24.6g/L total sugars. ABE production from fermentation
      of 25 g/L glucose and 25 g/L xylose was 9.9+/-0.4 and 9.6+/-0.4 g/L,
      respectively, suggesting that the culture was able to utilize xylose as
      efficiently as glucose. Production of only 9.3+/-0.5 g/L ABE (compared with 17.7
      g/L ABE from fermentation of 55 g/L glucose-control) from the XAD-4 treated SACFH
      suggested that some fermentation inhibitors may still be present following
      treatment. It is suggested that inhibitory components be completely removed from
      the SACFH prior to fermentation with C. beijerinckii BA101. In our fermentations,
      an ABE yield ranging from 0.35 to 0.39 was obtained, which is higher than
      reported by the other investigators.

PMID- 18061441
TI  - Effect of biogenic fermentation impurities on lactic acid hydrogenation to
      propylene glycol.
AB  - The effect of residual impurities from glucose fermentation to lactic acid (LA)
      on subsequent ruthenium-catalyzed hydrogenation of LA to propylene glycol (PG) is
      examined. Whereas refined LA feed exhibits stable conversion to PG over carbon
      supported ruthenium catalyst in a trickle bed reactor, partially refined LA from
      fermentation shows a steep decline in PG production over short (<40 h) reaction
      times followed by a further slow decay in performance. Addition of model
      impurities to refined LA has varying effects: organic acids, sugars, or inorganic
      salts have little effect on conversion; alanine, a model amino acid, results in a
      strong but reversible decline in conversion via competitive adsorption between
      alanine and LA on the Ru surface. The sulfur-containing amino acids cysteine and
      methionine irreversibly poison the catalyst for LA conversion. Addition of 0.1
      wt% albumin as a model protein leads to slow decline in rate, consistent with
      pore plugging or combined pore plugging and poisoning of the Ru surface. This
      study points to the need for integrated design and operation of biological
      processes and chemical processes in the biorefinery in order to make efficient
      conversion schemes viable.

PMID- 18061442
TI  - Biotransformation of phosphogypsum in wastewaters from the dairy industry.
AB  - The biotransformation of phosphogypsum by stationary cultures of sulphate
      reducing bacteria (SRB) in dairy wastewaters (sterile and non-sterile) enriched
      in phosphogypsum, was studied SRB were isolated from soil contaminated with
      petroleum-derived products and from wastewaters from the petroleum-refining
      industry, taking into account that these environments are characteristic for the
      bacteria of the studied group. The biotransformation products formed were
      investigated using biological and mineralogical methods. Sulphides in the
      cultures were determined using the iodometric method, sulphates with the hot
      barium method, COD by the dichromate method. Determinations involving post
      culture sediments and fluids, Ca, S, Sr and P were made using the following
      analytical procedures: IPC emission spectrometry with induced excitation in the
      medium and X-ray. Analysis of post-culture sediments was made using a DRON-2 X
      ray diffractometer. Eleven communities of microorganisms with varying degrees of
      effectiveness were obtained, biodegrading 58% to 98% of the organic contaminants
      in non-sterile wastewater, with simultaneous biotransformation of about 2.5 g
      phosphogypsum/L.

PMID- 18061443
TI  - Alpha-hydroxy amides as a novel class of bradykinin B1 selective antagonists.
AB  - Antagonism of the bradykinin B(1) receptor represents a potential treatment for
      chronic pain and inflammation. Novel antagonists incorporating alpha-hydroxy
      amides were designed that display low-nanomolar affinity for the human bradykinin
      B(1) receptor and good bioavailability in the rat and dog. In addition, these
      functionally active compounds show high passive permeability and low
      susceptibility to phosphoglycoprotein mediated efflux, predictive of good CNS
      exposure.

PMID- 18061444
TI  - 1-Toluene-sulfonyl-3-[(3'-hydroxy-5'-substituted)-gamma-butyrolactone]-indoles:
      synthesis, COX-2 inhibition and anti-cancer activities.
AB  - Indoles carrying a cyclic ester (gamma-butyrolactone) at C-3 position have been
      synthesized by the allylation of 3-indoleglyoxylate followed by iodocyclisation
      and the nucleophilic replacement of the iodo-group. Screening of these molecules
      for COX-2 inhibition and anti-cancer activities has identified compounds 10 and
      11 as highly potent and selective for COX-2 as well as showing remarkable anti
      cancer activities (better than that of indomethacin).

PMID- 18061445
TI  - Alpha,beta-cyclic-beta-benzamido hydroxamic acids: novel templates for the
      design, synthesis, and evaluation of selective inhibitors of TNF-alpha converting
      enzyme (TACE).
AB  - Selective inhibitors of TNF-alpha Converting Enzyme (TACE) based on (1R,2S)
      cyclopentyl, (3S,4S)-pyrrolidinyl, and (3R,4S)-tetrahydrofuranyl beta-benzamido
      hydroxamic acids have been synthesized and evaluated. This study has led to the
      discovery of novel inhibitors whose profiles include activity against TACE in an
      enzyme assay, potency in the suppression of LPS-stimulated TNF-alpha in human
      whole blood, selectivity against a panel of MMPs and oral bioavailability.

PMID- 18061446
TI  - A new series of neutral 5-substituted 4-anilinoquinazolines as potent, orally
      active inhibitors of erbB2 receptor tyrosine kinase.
AB  - Starting from initial lead 1 containing a basic 5-substituent, optimisation of
      the glycolamide-derived neutral 5-substituent led to potent inhibitors of erbB2
      with good pharmacokinetics. Representative compounds 19 and 21 inhibited
      phosphorylation of erbB2 in a mouse BT474C xenograft model after oral
      administration.

PMID- 18061447
TI  - A novel biotinylated diazirinyl ceramide analogue for photoaffinity labeling.
AB  - A novel photoreactive ceramide analogue, which contains (3
      trifluoromethyl)phenyldiazirinyl lipid and biotinylated sphingosine, was
      synthesized. The probe was recognized as an antigen by anti-ceramide antibody and
      as a substrate for sphingolipid ceramide N-deacylase. These results indicate that
      the probe may be useful as a photoaffinity-biotinylating agent in sphingolipid
      studies.

PMID- 18061448
TI  - Sulfonamide derivatives of bridgehead substituted bicyclo[4.2.1]nonanes as gamma
      secretase inhibitors.
AB  - Bridgehead substituted derivatives of bicyclo[4.2.1]nonanes were synthesized and
      shown to be potent inhibitors of gamma-secretase. Two related series were
      synthesized to explore the SARs. More potent compounds were found in the non
      benzofused series compared with the benzofused series. One compound from each
      series showed good exposure in the hepatic portal vein (HPV) following oral
      dosing to rats.

PMID- 18061449
TI  - Substrate specificity and diastereoselectivity of strictosidine glucosidase, a
      key enzyme in monoterpene indole alkaloid biosynthesis.
AB  - Strictosidine glucosidase (SGD) from Catharanthus roseus catalyzes the
      deglycosylation of strictosidine, an intermediate from which thousands of
      monoterpene indole alkaloids are derived. The steady-state kinetics of SGD with a
      variety of strictosidine analogs revealed the substrate preferences of this
      enzyme at two key positions of the strictosidine substrate. Additionally, SGD
      from C. roseus turns over both strictosidine and its stereoisomer vincoside,
      indicating that although this enzyme prefers the naturally occurring
      diastereomer, the enzyme is not completely diastereoselective. The implications
      of the substrate specificity of SGD in metabolic engineering efforts of C. roseus
      are highlighted.

PMID- 18061450
TI  - The first steps. The attack on the carbonyl carbon of pyridoxal cofactor in
      pyridoxal-dependent enzymes.
AB  - A study of the reaction between gaseous aldehydes and amines has implicated
      proton transfer from wall-associated water. Carbinolamine formation and
      subsequent dehydration to imine with assistance by wall associated hydroxyl
      bearing species has not previously been specifically suggested to obtain in the
      multitude of enzyme processes using pyridoxal cofactor. However, the data now
      available make it clear that imine formation in the active site of those systems
      requires at least one water or hydroxyl bearing amino acid for proton transfer.

PMID- 18061451
TI  - Optimization of the heterocyclic core of the quinazolinone-derived CXCR3
      antagonists.
AB  - A series of six-six and six-five fused heterocyclic CXCR3 antagonists has been
      synthesized and their activities evaluated in an [(125)I]-IP-10 displacement
      assay and an ITAC mediated in vitro cell migration assay. The pharmacokinetic
      properties of several top compounds have also been studied. This effort led to
      the discovery of compounds with increased potency and improved pharmacokinetic
      properties that could serve as useful tools to study the role of the CXCR3
      receptor in vivo.

PMID- 18061452
TI  - Chemotherapeutic bone-targeted bisphosphonate prodrugs with hydrolytic mode of
      activation.
AB  - Osseous tissues are considered to be limited as therapeutic target sites due to
      their biological properties. We have designed and synthesized two kinds of
      hydrolytically activated chemotherapeutic prodrugs containing bisphosphonate, a
      bone-targeting moiety. The first can be conjugated to drug molecules with an
      available hydroxy group; the drug is attached to the bisphosphonate component
      through an ester-labile linkage. The second is for use with drug molecules with
      amine functional group. In this case, a self-immolative linker is used to attach
      the drug to the bisphosphonate component through a carbonate-labile linkage. The
      concept was demonstrated using the drugs camptothecin, which has a hydroxy
      functional group, and tryptophan, which is a model molecule for a drug with amine
      functionality. Both prodrugs showed significant binding capability to
      hydroxyapatite, the major component of bone, and were hydrolytically activated
      under physiological conditions.

PMID- 18061454
TI  - Characterization of a novel S13F desmin mutation associated with desmin myopathy
      and heart block in a Chinese family.
AB  - Desmin myopathy was identified in a Chinese man with complete heart block and
      mild proximal and distal limb weakness. A novel heterozygous missense S13F
      mutation of the desmin gene was found to be associated with the myopathy. Family
      members carrying the mutation showed a similar or milder phenotype. The mutation
      is located at a protein kinase-C phosphorylation site within a highly conserved
      nonapeptide sequence in the head domain of the desmin protein. Expression of the
      mutant desmin cDNA in cell lines induced large desmin accumulations associated
      with preservation of a filamentous network.

PMID- 18061453
TI  - Danon disease: a novel Lamp-2 gene mutation in a family with four affected
      members.
AB  - This is a report of a family with four members affected with Danon disease and
      variable clinical presentations, including cardiomyopathy, skeletal muscle
      pathology, and hepatopathy. Analysis by electron microscopy of the quadriceps
      muscle from the proband and his brother showed abnormal mitochondria, and
      immunohistochemistry revealed no expression of LAMP-2 protein. This defect is due
      to a yet undescribed mutation located at the second nucleotide in the intron 8 of
      the Lamp-2 gene (c.1093+2 T>A) that generated exon 8 skipping confirmed at RNA
      level in the proband.

PMID- 18061455
TI  - Adjuvant and extended adjuvant use of aromatase inhibitors: reducing the risk of
      recurrence and distant metastasis.
AB  - In patients with early-stage breast cancer, all recurrences are associated with
      an increased risk of mortality, especially distant metastases. Adjuvant tamoxifen
      therapy for 5 years is effective in postmenopausal patients for the prevention of
      disease recurrence but is associated with increased risk of rare, potentially
      fatal adverse events such as endometrial cancer, stroke, and pulmonary embolism.
      Recently, randomized clinical trials have shown aromatase inhibitor therapy to be
      superior to tamoxifen therapy for the prevention of disease recurrence. Switching
      to an aromatase inhibitor after 2-3 years of tamoxifen treatment has been shown
      to provide superior disease-free survival compared with completing 5 years of
      tamoxifen. Among approved aromatase inhibitors (letrozole, anastrozole, and
      exemestane), letrozole is the only one approved as extended adjuvant therapy
      after completing 5 years of tamoxifen. These results suggest that 10 years of
      adjuvant endocrine therapy is superior to 5 years of tamoxifen alone.

PMID- 18061456
TI  - Anterior versus combined anterior and posterior fixation/fusion in the treatment
      of distraction-flexion injury in the lower cervical spine.
AB  - This study compared the results of combined anterior and posterior
      fixation/fusion with those of anterior fixation/fusion alone through a
      retrospective review of 50 patients with a distraction flexion injury of the
      cervical spine. Group A (n=28) had unilateral facet joint subluxation or
      dislocation (Allen stage I or II) and anterior fixation/fusion alone. Group B
      (n=10) had bilateral dislocation (Allen stage III) and anterior fixation/fusion
      alone. Group C (n=5) had unilateral subluxation or dislocation and combined
      anterior and posterior fixation/fusion. Group D (n=7) had bilateral dislocation
      or total dislocation (Allen stage III or IV) and combined anterior and posterior
      fixation/fusion. The following parameters were analyzed: the change in the
      vertebral height and Cobb's angle, neurologic recovery, fusion time, fusion rate,
      surgery time, and the rate of complications. The mean fusion time was 3.75+/
      2.10, 6.00+/-2.82, 3.60+/-1.34, and 3.85+/-2.26 months in groups A, B, C, and D,
      respectively. Group B had a significantly longer mean fusion time than groups A
      and D (Mann-Whitney U-test, P=0,012, P=0.014). There was a significant difference
      in the operation time between groups A and B and groups C and D. There were no
      significant differences in the changes in vertebral height and Cobb's angle,
      fusion rate, and neurologic recovery. The complications encountered were three
      cases of distal screw loosening in group A (n=2) and B (n=1), and three cases of
      delayed union in group A (n=2) and B (n=1). There were no complications in groups
      C and D. In those with a bilateral dislocation, the fusion time was increased
      when only anterior fixation/fusion had been performed but the clinical results,
      such as neurologic recovery and complications, were similar in the four groups.
      Overall, anterior fixation/fusion alone in a bilateral dislocation is recommended
      as an alternative method.

PMID- 18061457
TI  - A comparative study of treatment for brain edema: magnesium sulphate versus
      dexamethasone sodium phosphate.
AB  - Treatments for brain edema are important and one of the major options is
      corticosteroids. Cell membrane stabilization and prevention of formation of free
      radicals are the main mechanisms of action of steroids in edema treatment. As an
      alternative therapeutic agent, magnesium sulphate has been used for its
      neuroprotective effect in various injury models. In our animal model of brain
      injury, cold has been used in Sprague-Dawley rats. After brain injury, magnesium
      sulphate (600 mg/kg) or dexamethasone sodium phosphate (0.2 mg/kg) were
      administered to experimental groups. The degree of brain edema and lipid
      peroxidation was evaluated using the wet-dry weight method, the determination of
      malondialdehyde (MDA) levels and an ultrastructural grading system. Magnesium
      sulphate treatment was found to be the most effective choice due to the absence
      of side effects and comparable efficacy to corticosteroids.

PMID- 18061458
TI  - Protein phosphatase inhibitory activity of tautomycin photoaffinity probes
      evaluated at femto-molar level.
AB  - Herein we describe the further improvement of our in-house developed firefly
      bioluminescence assay system for the determination of inhibition of protein
      phosphatase (PP). The advantage with the new system is higher sensitivity as well
      as being time and sample efficient. The inhibition activity of tautomycin with
      PP1gamma was determined using the upgraded test system and Ki was found to be 4.5
      nM, which compare favorably with the activity reported previously by others using
      different methods. The test system was then used in order to determine the
      activity of nine tautomycin (TTM) photoaffinity probes. One of the TTM
      photoaffinity probes (anti-10) was found to possess higher activity than the
      natural product itself with a Ki of 3.4 nM, while the remaining photoaffinity
      probes were found to possess Ki in the range of 8.0-213 nM.

PMID- 18061459
TI  - Antiproliferative effects on human tumor cells and rat aortic smooth muscular
      cells of 2,3-heteroarylmaleimides and heterofused imides.
AB  - A series of 2,3-heteroarylmaleimides 9 and polyheterocondensed imides 12 were
      prepared in good yields and short reaction time using a very efficient procedure
      consisting in the condensation of the corresponding anhydrides and N,N
      diethylethylenediamine and microwave heating. The antiproliferative activity of
      the novel molecules was tested against human tumor cells (NCI-H460 lung
      carcinoma) and rat aortic smooth muscle cells (SMCs). The IC50 values for the
      novel molecules ranged from 0.08 to 13.9 microM in SMCs, and from 0.84 to 9
      microM in the tumor cell line. The activity profile for compounds 9 and 12 is
      comparable to that obtained for amonafide in NCI-H460, except for fused imides
      12b,i which proved to be about 10-fold more potent. Whereas, in rat SMCs, only
      the compound 12b was shown to be 10-fold more potent than amonafide. Instead 12c
      is equipotent to amonafide. These results suggest that the extended pi-system and
      the kind of heteroatom are essential in the binding with the molecular target.

PMID- 18061460
TI  - Synthesis, biological evaluation and molecular modelling studies of
      methyleneimidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase
      17,20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure.
AB  - Novel chemical entities were prepared via Suzuki and S(N) reaction as AC-ring
      substrate mimetics of CYP17. The synthesised compounds 1-31 were tested for
      activity using human CYP17 expressed in Escherichia coli. Promising compounds
      were tested for selectivity against hepatic CYP enzymes (3A4, 2D6, 1A2, 2C9,
      2C19, 2B6). Two potent inhibitors (27, IC50 = 373 nM/28, IC50 = 953 nM) were
      further examined in rats regarding their effects on plasma testosterone levels
      and their pharmacokinetic properties. Compound 28 was similarly active as
      abiraterone and showed better pharmacokinetic properties (higher bioavailability,
      t(1/2) 9.5 h vs 1.6 h). Docking studies revealed two new binding modes different
      from the one of the substrates and steroidal inhibitors.

PMID- 18061461
TI  - 5,5,6-Fused tricycles bearing imidazole and pyrazole 6-methylidene penems as
      broad-spectrum inhibitors of beta-lactamases.
AB  - Beta-lactamases are serine- and metal-dependent hydrolases, produced by the
      bacteria as defense against beta-lactam antibiotics. Commercially available
      inhibitors such as clavulanic acid, sulbactam, and tazobactam, which are
      currently used in the hospital settings, have reduced activity against newly
      emerging beta-lactamases. Bacterial production of diverse beta-lactamases
      including class-A, class-C, and ESBLs has motivated several research groups to
      search for inhibitors with a broader spectrum of activity. Previously, several
      novel 6-methylidene penems bearing, [5,5] [5,6] and [5,5,5] heterocycles have
      been synthesized in our laboratory and were shown to be potent and broad-spectrum
      beta-lactamase inhibitors. As a continuation of our previous work and in order to
      extend the structure-activity relationships, in this paper, we describe herein
      the synthesis and in vitro, in vivo activities of several novel 5,5,6-fused
      tricyclic heterocycles attached to the 6-methylidene penem core. The compounds
      presented in the current paper are potent and broad-spectrum inhibitors of the
      TEM-1 and AmpC beta-lactamases. In combination with piperacillin, their in vitro
      activities showed enhanced susceptibility to class A- and C-resistant strains
      studied in various bacteria. Some of the newly synthesized compounds such as 12a
      c were shown to have in vivo activity in the acute lethal infection model against
      TEM-1 producing organisms. The 5,5,6-fused heterocyclic ring cores such as 21,
      25, and 35 reported here are hitherto unknown in the literature.

PMID- 18061462
TI  - Amphiphilic chitosan nanosphere: studies on formation, toxicity, and guest
      molecule incorporation.
AB  - Amphiphilic chitosan developed by conjugating hydrophobic phthalimido groups and
      hydrophilic poly (ethylene glycol) chains gives a well-dispersed colloidal
      solution in polar solvents and shows a regular nano-sized spherical structure (
      approximately 200 nm) with negatively charged surface (-31.24+/-4.85 mV). An in
      vivo acute oral toxicity test confirms the non-toxicity of the chitosan
      nanosphere with LD(50) higher than 2000 mg/kg body weight. A success of
      incorporating amine molecules into the nanosphere declares that the heterogeneous
      incorporation system is more effective than the homogeneous ones. The study on
      guest molecule incorporation using alkylamines and carboxylic acid as models
      suggests requirements that the guest be hydrophobic and positively charged. TGA
      study clarifies that the weight loss at 250-300 degrees C relating to the amount
      of guest incorporation via heterogeneous system is as high as 42.3%, whereas
      those of homogeneous systems are about 16.86-28.27%. The nanosphere size is
      significantly changed after guest incorporation, that is, from 200 nm to
      approximately 500-1000 nm.

PMID- 18061463
TI  - Cytoplasmic RNA and nuclear changes detected cytochemically during the
      degeneration of salivary glands of the tick Rhipicephalus sanguineus (Latreille,
      1806) (Acari, Ixodidae).
AB  - The present study reports cytochemistry data about salivary glands of females
      (unfed, engorged, and at day three post-engorgement) and males (unfed, at day
      seven post-attachment, and at days three and seven post-detachment from the host)
      of the tick Rhipicephalus sanguineus. The results revealed nuclear changes in
      engorged females and at day three post-engorgement, and in males in all stages
      (except unfed). These changes were more prominent in females. Cytoplasmic changes
      were also observed in cells of all acini of males and females. In types II and
      III acini of engorged females, nuclear changes were observed in the shape
      (irregular, with blebs, fragmenting or fragmented), size (enlarged or reduced),
      and arrangement and condensation level of chromatin (marginal or as blebs).
      Changes were also detected in nucleoli, regarding their shape (fragmenting or
      fragmented), size (enlarged), and location (central, marginal or as blebs). Some
      nucleoli were also compacted or disorganized. In females at day three pos
      engorgement, all acini exhibited similar changes to those observed in engorged
      females. RNA staining was stronger in cells of engorged females than those at day
      three post-engorgement. In males at day seven post-attachment, cells of types II,
      III, IV acini presented changes in the size of the nucleus and condensation level
      of chromatin similar to those of females. The shape of the nucleus was round,
      irregular or undergoing fragmentation, and the chromatin was located at the
      margin or throughout the nucleus. The changes in the nucleolus were similar to
      those of females, regarding size and organization, although round-shaped and in
      the central location. In males at day three post-detachment, cells of all acini
      exhibited nuclear changes similar to those of males at day seven post-attachment,
      in addition to the fragmentation of the nucleolus. At day seven post-detachment,
      changes were detected in all acini similar to the observed in males at day seven
      post-attachment. Regarding cytoplasmic RNA, staining was prominent in males at
      day seven post-attachment and weak in those at day seven post-detachment from the
      host. In females as well as males, different RNA staining patterns in the
      cytoplasm and nuclear changes characterized apoptotic cell death.

PMID- 18061464
TI  - A simplified gamma-ray self-attenuation correction in bulk samples.
AB  - Gamma-ray spectrometry is a very powerful tool for radioactivity measurements.
      For accurate gamma-ray spectrometry, certain correction measures should be
      considered, for instance, systematic uncertainty in the photo-peak efficiency due
      to the differences between the matrix (density and chemical composition) of the
      reference and the other bulk samples. Therefore, gamma-ray attenuation correction
      factors are of major concern for precise gamma-ray spectrometry. Simple practical
      correction for the photo-peak efficiency, due to discrepancies in both the
      samples' matrices and densities (self-attenuation), is performed in this study.
      This study suggests a brief measurement of relative photons transmission through
      both reference and unknown bulk samples where the variations of photon
      transmissions are assumed to be linearly correlated to the samples' densities.
      Specific correction factors would be produced for each analyzed sample to be
      considered when their activities are calculated. Practically, the suggested
      method was verified and succeeded in improving the obtained results.

PMID- 18061465
TI  - Increased freezing tolerance through up-regulation of downstream genes via the
      wheat CBF gene in transgenic tobacco.
AB  - The wheat (Triticum aestivum L.) CBF gene family is assumed to play important
      roles in development of low-temperature and freezing tolerance through activation
      of the downstream Cor/Lea genes. However, no direct evidence shows association of
      the wheat CBF genes with stress tolerance or any interaction between wheat CBF
      transcription factors and Cor/Lea gene activation. Here, we introduced Wcbf2, one
      of the wheat CBF genes, into the tobacco (Nicotiana tabacum L.) genome.
      Expression of Wcbf2 significantly increased the level of freezing tolerance in
      the transgenic tobacco plants without phenotypic retardation, and altered the
      expression patterns of tobacco genes, including cold-responsive genes. A
      transgenic tobacco plant expressing Wcbf2 was crossed to other transgenic plants
      expressing a GUS reporter gene under control of the wheat Cor/Lea gene promoter.
      Analysis of the F(1) plants showed that the WCBF2 protein positively regulated at
      least the expression of Wdhn13 and Wrab17. These results strongly indicate that
      WCBF2 functions as a transcription factor in the development of freezing
      tolerance in common wheat.

PMID- 18061466
TI  - Tuber development phenotypes in adapted and acclimated, drought-stressed Solanum
      tuberosum ssp. andigena have distinct expression profiles of genes associated
      with carbon metabolism.
AB  - A drought screen identified accessions of Solanum tuberosum ssp. andigena that
      showed varying degrees of physiological acclimation or adaptation to repeated
      drought stress. The accessions also showed variable tuber phenotypes from small
      tubers that failed to develop in an accession that showed photosynthetic
      adaptation to normal tubers in an accession with a phenotype showing some degree
      of photosynthetic adaptation and acclimation. Using microarray data, we
      correlated the expression of genes associated with carbon metabolism with the
      tuber development phenotypes under drought. Genes associated with sucrose and
      starch metabolism showed responses consistent with starch deficiency in the
      adapted accession and normal starch deposition in the intermediate accession.
      Starch phosphorylase and glycogen bound starch synthase were induced in the
      adapted accession, which had abnormal tuber development. Genes associated with
      trehalose were induced in the intermediate accession with normal tuber
      development. Genes associated with respiration were also induced in the
      intermediate accession, and a pattern compatible with the existence of a 3PGA
      recovery pathway was revealed. Expression of thioredoxin genes also correlated
      with tuber development phenotypes under drought stress. The data suggest
      differential regulation of starch deposition in accessions of Andigena with
      different abilities to respond to drought stress.

PMID- 18061467
TI  - Characterization and expression of a vacuolar Na(+)/H(+) antiporter gene from the
      monocot halophyte Aeluropus littoralis.
AB  - Plant vacuolar Na(+)/H(+) antiporter plays an important role in salt tolerance.
      In order to understand the molecular basis of vacuolar Na(+)/H(+) antiporter
      responded to salinity and reveal a possible role of salt tolerance in monocots, a
      vacuolar Na(+)/H(+) antiporter gene (AlNHX) was isolated by reverse transcription
      PCR and RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE) based on
      the homology from Aeluropus littoralis (Gouan) Parl, a graminaceous halophyte.
      The AlNHX sequence contained 2706bp with an open read frame of 1623bp and the
      deduced transcripts encoding 540 amino acids shared a high homology with those
      putative vacuolar Na(+)/H(+) antiporters of higher plants. AlNHX was predicted
      containing ten putative hydrophobic regions, which was different with AtNHX1 and
      OsNHX1. DNA gel blot analysis indicated that there were two or three copies of
      AlNHX in the A. littoralis genome. The increased transcript levels of AlNHX were
      much higher in roots than that in shoots under salt stress. In addition,
      overexpression of AlNHX in tobacco conferred high salt tolerance to the
      transgenic plants. The analysis of ion contents indicated that under high salt
      stress for one month, the transgenic plants compartmentalized more Na(+) in the
      roots and kept a relative high K(+)/Na(+) ratio in the leaves compared with wild
      type plants.

PMID- 18061468
TI  - Induction chemoradiotherapy prior to surgery for non-small cell lung cancer
      invading the left atrium.
AB  - We present a case of a 58-year-old man with diagnosis of lung adenocarcinoma
      invading the left atrium. He was treated with induction chemoradiotherapy for
      T4N1M0 disease, showing objective response. Then, a left upper lobectomy with a
      partial resection of the left atrium was performed without cardiopulmonary
      bypass. No residual tumor cells existed in the resected specimens, showing
      pathological complete response. Our case suggests that induction
      chemoradiotherapy prior to surgery can be an appropriate strategy among carefully
      selected patients with non-small cell lung cancer invading the left atrium.

PMID- 18061469
TI  - Management of traumatic aortic rupture: endovascular is the winner.

PMID- 18061470
TI  - Reduction of airspace after lung resection through controlled paralysis of the
      diaphragm.
AB  - OBJECTIVES: Residual airspace following thoracic resections is a common clinical
      problem. Persistent air leak, prolonged drainage time, and reduced hemostasis
      extend hospital stay and morbidity. We report a trial of pharmacologic-induced
      diaphragmatic paralysis through continuous paraphrenic injection of lidocaine to
      reduced residual airspace. The objectives were confirmation of diaphragmatic
      paralysis and possible procedure related complications. METHODS: Six eligible
      patients undergoing resectional surgery (lobectomy or bilobectomy) were included.
      Inclusion criteria consisted of: postoperative predicted FEV1 greater than 1300
      ml, right-sided resection, absence of parenchymal lung disease, no class III
      antiarrhythmic therapy, absence of hypersensitivity reactions to lidocaine, no
      signs of infection, and informed consent. Upon completion of resection an
      epidural catheter was attached in the periphrenic tissue on the proximal
      pericardial surface, externalized through a separate parasternal incision, and
      connected to a perfusing system injecting lidocaine 1% at a rate of 3 ml/h (30
      mg/h). Postoperative ICU surveillance for 24h and daily measurement of vital
      signs, drainage output, and bedside spirometry were performed. Within 48 h
      fluoroscopic confirmation of diaphragmatic paralysis was obtained. The catheter
      removal coincided with the chest tube removal when no procedural related
      complications occurred. RESULTS: None of the patients reported respiratory
      impairment. Diaphragmatic paralysis was documented in all patients. Upon removal
      of catheter or discontinuation of lidocaine prompt return of diaphragmatic
      motility was noticed. Two patients showed postoperative hemodynamic irrelevant
      atrial fibrillation. CONCLUSION: Postoperative paraphrenic catheter
      administration of lidocaine to ensure reversible diaphragmatic paralysis is safe
      and reproducible. Further studies have to assess a benefit in terms of reduction
      in morbidity, drainage time, and hospital stay, and determine the patients who
      will profit.

PMID- 18061471
TI  - Atria assist device to restore transport function of fibrillating atrium.
AB  - OBJECTIVE: The Maze procedure can restore sinus rhythm in patients suffering from
      chronic atrial fibrillation but often fails to restore the mechanical function of
      the atrium, the so-called atrial kick and requires long-term anticoagulation most
      of the time. A micro motorless pump (Atripump) based on artificial muscle
      technology positioned on the external surface of the atrium could compress the
      heart chamber, restoring atrium transport function. A bench model reproducing the
      mechanical function of human atrium and human environment has been developed to
      assess the circulatory support that such a pump can provide. METHODS: Atripump
      (Nanopowers SA, Switzerland) is a dome-shape, silicone-coated nitinol actuator to
      be sutured on the external surface of the atrium. A pacemaker-like control unit
      drives the actuator and manages the external compression of the atrium. The bench
      model consists of an open circuit made of rubber bladder, 60 cc in volume,
      connected to a vertically positioned and scaled tube that is filled at different
      levels reproducing changes in cardiac pre-load and after-load. The pump was
      placed on the outer surface of the bladder and both were immersed in water having
      a constant temperature of 37 degrees C. Pressure, volume and temperature at the
      interface dome-bladder were recorded. RESULTS: Pump ran 24 h for three
      consecutive months. During the experiment, no technical failure occurred and the
      pressure and volume values were repeatable during the experience. Nitinol fatigue
      was assessed measuring the wire's electric resistance that remained 400+/-10
      Omega/m. Contraction rate was 1 Hz with power supply of 12 V, 400 m and heating
      time of 300 ms. Pre-load ranged from 11 to 15 mmHg. When inserted in the bath at
      37+/-0.5 degrees C, maximal temperature between silicone membrane and rubber
      bladder was 39 degrees C. Maximal volume pumped was 492 ml/min. CONCLUSIONS: This
      artificial muscle pump can reproduce the mechanical effect of a normal human
      atrium. It is compact, reliable and follows the Starling law. The surface
      temperature is in the physiologic range and it could represent a new tool to
      restore the atrial kick in persistent atrial fibrillation.

PMID- 18061472
TI  - Haemodynamic complications after pneumonectomy: atrial inflow obstruction and
      reopening of the foramen ovale.
AB  - BACKGROUND: Haemodynamic impairments after pneumonectomy are rare complications
      and present in different forms. Due to a low awareness of these potential
      complications their diagnosis is difficult and often established late. The most
      important forms are: firstly reopening of a previously closed foramen ovale (PFO)
      caused by a combination of changed anatomic position of the left atrium and
      elevated pulmonary artery pressure leading to a significant right-left shunt;
      secondly diaphragmatic relaxation can lead to a dislocation of the liver into the
      right hemithorax, compressing the right atrium with subsequent inflow
      obstruction. METHODS: We retrospectively analysed our patient cohort from 1997 to
      2006 for occurrence of haemodynamic complications requiring surgical intervention
      after pneumonectomy. RESULTS: Five hundred and forty-six pneumonectomies were
      performed in our centre during the observation period. Five patients (1 female, 4
      male, age 59+/-9 years) with haemodynamic complications were identified. Two of
      those patients were referred with haemodynamic complications after pneumonectomy
      was performed in a peripheral centre. All patients had undergone right
      pneumonectomy for NSCLC (n=4) or atypical carcinoid (n=1). Two patients were
      readmitted 3 months and 2 years postoperatively due to increasing platypnoea and
      orthodeoxia. After closure of the reopened foramen ovale, which was found as the
      underlying pathological mechanism, respiratory symptoms were resolved. One
      patient required reintubation 2h postoperatively; after surgical closure of a PFO
      the respiratory situation significantly improved. One patient was readmitted due
      to right atrial inflow obstruction 17 months after right pneumonectomy.
      Underlying cause was a severe diaphragmatic relaxation with compression of the
      atrium by the liver. After diaphragmatic plication all symptoms resolved. However
      1 year thereafter reoperation for recurrence of diaphragmatic elevation was
      required. One patient was readmitted 3 months after pneumonectomy and partial
      atrial resection for cyanosis and dyspnoea. Diagnostics revealed a PFO and a
      massive raise of the right diaphragm with compression of the right atrium. After
      surgical correction of the contorted foramen ovale and diaphragmatic plication,
      symptoms vanished. CONCLUSION: Haemodynamic alterations due to a reopened foramen
      ovale or right atrial inflow obstruction are rare, however they are severe
      complications after pneumonectomy. They occur at variable points in time after
      pneumonectomy. Diagnostic efforts are often made at a late stage due to a low
      awareness of the problem. Closure of the PFO either surgical or interventional
      and/or plication of the elevated diaphragm are mandatory. In our experience these
      complications occur only after right pneumonectomy.

PMID- 18061473
TI  - Act1 modulates autoimmunity through its dual functions in CD40L/BAFF and IL-17
      signaling.
AB  - Coordinated regulation of T and B cell-mediated immune responses plays a critical
      role in the control and modulation of autoimmune diseases. This review is focused
      on the adapter molecule Act1 and its regulation of autoimmunity through its
      impact on both T and B cell-mediated immune responses. Whereas Act1 molecule is
      an important negative regulator for B cell-mediated humoral immune responses
      through its function in CD40L and BAFF signaling, recent studies have shown that
      Act1 is also a key positive signaling component for IL-17 signaling pathway,
      critical for T(H)17-mediated autoimmune and inflammatory responses. The dual
      functions of Act1 are evident in Act1-deficient mice that displayed B cell
      mediated autoimmune phenotypes (including dramatic increase in peripheral B
      cells, lymphadenopathy and splenomegaly, hypergammaglobulinemia and Sjogren's
      disease in association with Lupus Nephritis), but showed resistance to T(H)17
      dependent EAE and colitis. Such seemingly opposite functions of Act1 in CD40
      BAFFR and IL-17R signaling are orchestrated by different domains in Act1. Whereas
      Act1 interacts with the IL-17R through the C-terminal SEFIR domain, Act1 is
      recruited to CD40 and BAFFR indirectly, which is mediated by TRAF3 through the
      TRAF binding site in Act1. Such delicate regulatory mechanisms may provide a
      common vehicle to promote balance between host defense to pathogens and tolerance
      to self.

PMID- 18061474
TI  - The expression of IL-20 and IL-24 and their shared receptors are increased in
      rheumatoid arthritis and spondyloarthropathy.
AB  - The purpose of this study was to analyze the expression of the two
      proinflammatory cytokines IL-20 and IL-24 and their shared receptors in
      rheumatoid arthritis and spondyloarthropathy. IL-20 was increased in plasma of
      rheumatoid arthritis patients compared with osteoarthritis patients and IL-24 was
      increased in synovial fluid and plasma of rheumatoid arthritis and
      spondyloarthropathy patients compared with osteoarthritis patients. IL-20 and IL
      24 mRNA was only present at low levels in the synovium. In the synovial membrane,
      IL-20 protein was present in mononuclear cells and neutrophil granulocytes
      whereas IL-24 protein was observed in endothelial cells and mononuclear cells. IL
      20 receptor type 1 and IL-22 receptor were expressed by granulocytes in the
      synovial fluid. In synovial fluid mononuclear cell cultures, stimulation with
      recombinant human IL-20 or recombinant human IL-24 induced monocyte
      chemoattractant protein 1 (CCL2/MCP-1) secretion, but not tumour necrosis factor
      alpha mRNA synthesis or IL-6 secretion. Both IL-20 and IL-24 showed correlations
      to CCL2/MCP-1 in plasma from rheumatoid arthritis and spondyloarthropathy
      patients. This study associates IL-20 and IL-24 to the synovium of rheumatoid
      arthritis and spondyloarthropathy and results indicate that the two cytokines
      contribute to disease pathogenesis through recruitment of neutrophil granulocytes
      and induction of CCL2/MCP-1.

PMID- 18061475
TI  - Improved mass accuracy for higher mass peptides by using SWIFT excitation for
      MALDI-FTICR mass spectrometry.
AB  - Stepwise-external calibration has previously been shown to produce sub part-per
      million (ppm) mass accuracy for the MALDI-FTICR/MS analyses of peptides up to m/z
      2500. The present work extends these results to ions up to m/z 4000. Mass
      measurement errors for ions of higher mass-to-charge are larger than for ions
      below m/z 2500 when using conventional chirp excitation to detect ions. Mass
      accuracy obtained by using stored waveform inverse Fourier transform (SWIFT)
      excitation was evaluated and compared with chirp excitation. Analysis of
      measurement errors reveals that SWIFT excitation provides smaller deviations from
      the calibration equation and better mass accuracy than chirp excitation for a
      wide mass range and for widely varying ion populations.

PMID- 18061476
TI  - Tandem MS can distinguish hyaluronic acid from N-acetylheparosan.
AB  - Isobaric oligosaccharides enzymatically prepared from hyaluronic acid (HA) and N
      acetylheparosan (NAH), were distinguished using tandem mass spectrometry. The
      only difference between the two series of oligosaccharides was the linkage
      pattern (in HA 1-->3 and in NAH 1-->4) between glucuronic acid and N
      acetylglucosamine residues. Tandem mass spectrometry afforded spectra in which
      glycosidic cleavage fragment ions were observed for both HA and NAH
      oligosaccharides. Cross-ring cleavage ions 0,2An and 0,2An-h (n is even number)
      were observed only in GlcNAc residues of NAH oligosaccharides. One exception was
      an 0,2A2 ion fragment observed for the disaccharide from HA. These cross-ring
      cleavage fragment ions are useful to definitively distinguish HA and NAH
      oligosaccharides.

PMID- 18061477
TI  - Hydrogen and trimethylsilyl transfers during EI mass spectral fragmentation of
      hydroxycarboxylic and oxocarboxylic acid trimethylsilyl derivatives.
AB  - This paper, describing electron ionization mass spectral fragmentation of some
      hydroxycarboxylic and oxocarboxylic acid trimethylsilyl derivatives, focuses on
      the formation of fragment ions resulting from the interactions between the two
      functionalities of these compounds. These interactions result in the formation of
      fragment ions at [CH2=C(OTMS)2]+., [CH2=CHC(OTMS)=OTMS]+, [M-31]+, [M-105]+, and
      [M-RCHO]+. in the case of hydroxycarboxylic acid trimethylsilyl derivatives of
      formula RCHOTMS(CH2)nCOOTMS and at [RC(OTMS)=CH2]+., [RC(=OTMS)CH=CH2]+, and [M
      RC(=O)CH2]+ in the case of oxocarboxylic acid trimethylsilyl esters of formula
      RC(=O)(CH2)nCOOTMS. Some of these fragmentations appeared to be sufficiently
      specific to be used to characterize these compounds. Several fragmentation
      pathways involving trimethylsilyl and hydrogen transfers were proposed to explain
      the formation of these different fragment ions and were substantiated by
      deuterium labeling.

PMID- 18061478
TI  - Structural characterization of recombinant human CD81 produced in Pichia
      pastoris.
AB  - Human CD81 (hCD81) protein has been recombinantly produced in the methylotrophic
      yeast Pichia pastoris. The purified protein, produced at a yield of 1.75 mg/L of
      culture, was shown to interact with Hepatitis C virus E2 glycoprotein.
      Immunofluorescent and flow cytometric staining of P. pastoris protoplasts with
      monoclonal antibodies specific for the second extracellular loop (EC2) of hCD81
      confirmed the antigenicity of the recombinant molecule. Full-length hCD81 was
      solubilized with an array of detergents and subsequently characterized using
      circular dichroism (CD) and analytical ultracentrifugation. These biophysical
      techniques confirmed that the protein solution comprises a homogenous species
      possessing a highly-defined alpha-helical secondary structure. The predicted
      alpha-helical content of the protein from CD analysis (77.1%) fits remarkably
      well with what would be expected (75.2%) from knowledge of the protein sequence
      together with the data from the crystal structure of the second extracellular
      loop. This study represents the first biophysical characterization of a full
      length recombinant tetraspanin, and opens the way for structure-activity analyses
      of this ubiquitous family of transmembrane proteins.

PMID- 18061479
TI  - Electron tomography of vitreous sections from cultured mammalian cells.
AB  - Cryo-electron tomography of appropriately thin, frozen-hydrated biological
      specimens has excellent potential for investigating the 3D macromolecular
      architecture of eukaryotic cells and tissues. Since cardiomyocytes are too thick
      to be visualised in an intact state, we grew immortalised cell line HL-1 to sub
      confluency and harvested the cells by enzymatic detachment prior to hyperbaric
      freezing, ultramicrotomy, and tomography. We improved the efficiency of
      tomographic acquisition from vitreous cryosections by implementing two new
      features: (1) fluorescence microscopy at cryogenic temperatures to search for
      features of interest without expending any of the tolerable electron dose on
      secondary (non-imaging) tasks, and (2) the use of colloidal gold as fiducial
      markers. Vital fluorescent staining and subsequent cryo-fluorescence microscopy
      of vitreous sections were used to localise mitochondria lying in positions
      suitable for acquiring tilt series, taking into account section flatness,
      presence of contamination and proximity to grid bars. To provide a simple and
      robust means of aligning tomograms, we developed a universally applicable
      protocol for depositing colloidal gold onto vitreous sections, analogous to the
      method for applying quantum dots described by Masich et al. [Masich, S., Ostberg,
      T., Norlen, L., Shupliakov, O., Daneholt, B., 2006. A procedure to deposit
      fiducial markers on vitreous cryo-sections for cellular tomography. J. Struct.
      Biol. 156, 461-468]. Tomograms of thin sections (nominal thickness 65-85 nm) of
      cardiac mitochondria revealed the interconnectivity of cristae and junctions with
      the inner mitochondrial membrane. In some cases, ATP synthases could be
      identified without ambiguity. These findings confirm the feasibility of
      investigating the structural biology of mammalian cells in three dimensions and
      at a resolution of 6-8 nm.

PMID- 18061480
TI  - Electromyographic mapping of the erector spinae muscle with varying load and
      during sustained contraction.
AB  - The purpose of the study was to explore changes in the spatial distribution of
      erector spinae electromyography amplitude during static, sustained contractions
      and during contractions of increasing load. Surface electromyographic (EMG)
      signals were detected from nine healthy subjects using a grid of 13 x 5
      electrodes placed unilaterally over the lumbar erector spinae musculature.
      Subjects stood in a 20 degrees forward flexed position and performed: (1) six 20
      s long contractions with loads ranging from 2.5 kg to 12.5 kg (2.5 kg increments)
      and (2) a 6 min sustained contraction with 7.5 kg load. Root mean square (RMS)
      and mean power spectral frequency (MNF) were computed from the recorded EMG
      signals. EMG RMS increased (P<0.0001) and MNF remained constant during
      contractions of increased load. During the sustained contraction, MNF decreased
      (P<0.0001) and RMS did not change over time. The centroid (center of activity) of
      the RMS map shifted caudally (P<0.0001) with time during the sustained
      contraction but did not change with varying load. These results suggest a change
      in the distribution of erector spinae muscle activity with fatigue and a uniform
      distribution of muscle activation across loads.

PMID- 18061481
TI  - Intrinsic and extrinsic analysis in computational anatomy.
AB  - We present intrinsic and extrinsic methods for studying anatomical coordinates in
      order to perform statistical inference on random physiological signals F across
      clinical populations. In both intrinsic and extrinsic methods, we introduce
      generalized partition functions of the coordinates, psi(x), x epsilon M, which
      are used to construct a random field of F on M as statistical model. In the
      intrinsic analysis, such partition functions are built intrinsically for
      individual anatomical coordinate based on Courant's theorem on nodal analysis via
      self-adjoint linear elliptic differential operators. In contrast, the extrinsic
      method needs only one set of partition functions for a template coordinate
      system, and then applies to each anatomical coordinate system via diffeomorphic
      transformation. For illustration, we apply both intrinsic and extrinsic methods
      to a clinical study: cortical thickness variation of the left cingulate gyrus in
      schizophrenia. Both methods show that the left cingulate gyrus tends to become
      thinner in schizophrenia relative to the healthy control population. However, the
      intrinsic method increases the statistical power.

PMID- 18061482
TI  - Regionally-specific adaptation dynamics in human object areas.
AB  - Functional magnetic resonance adaptation (fMR-A, also termed repetition
      suppression) is a reduction in activity due to repeated image presentations which
      has been extensively studied in human visual areas. Here we tested whether fMR-A
      dynamics during sustained image presentations is determined by cortical region or
      by stimulus category. Nine subjects were scanned while viewing a long sustained
      presentation of a single face or a house image. Attentional level was maintained
      throughout the presentation by a demanding contrast detection task. Our results
      show a clear regional differentiation in adaptation dynamics within high-level
      visual cortex -- especially in the ventral stream. Face-selective regions showed
      an initial adaptation effect followed by a sustained level of activity for both
      face and house images. In contrast, activity in house-related regions showed a
      faster initial decline for houses, which reached essentially to baseline for the
      non-optimal, face images. The object-related lateral occipital (LO) region
      exhibited an adaptation profile similar to the face-selective regions.
      Importantly, within each region, the rate of signal decline from the peak
      activation was independent of the viewed category (preferred or non-preferred),
      and this was true for parietal and frontal regions as well. Thus, our results
      demonstrate that the functional differentiation in ventral stream regions is
      evident not only in their functional selectivity but also in their adaptation
      dynamics. Our results suggest regional rather than stimulus specificity with
      regard to cortical computations. These results demonstrate that the adaptation
      effect can in fact be compatible with models positing a tight correlation between
      activity levels and perceptual states.

PMID- 18061483
TI  - The subcortical role of language processing. High level linguistic features such
      as ambiguity-resolution and the human brain; an fMRI study.
AB  - In the present study, we were interested in the neurofunctional representations
      of ambiguity processing by using functional magnetic resonance imaging (fMRI).
      Twelve right-handed, healthy adults aged between 21 and 29 years (6 male, 6
      female) underwent an ambiguity resolution task with 4 different conditions
      (dominant vs. non-dominant; dominant vs. distractor; non-dominant vs. distractor;
      distractor vs. distractor). After subtraction of the corresponding control task
      (distractor vs. distractor) we found significant activation especially in the
      thalamus and some parts of the basal ganglia (caudate nucleus, putamen). Our
      findings implicate a participation of the thalamus and other basal ganglia
      circuits in high level linguistic functions and match with theoretical
      considerations on this highly controversial topic. Subcortical neural circuits
      probably become activated when the language processing system cannot rely
      entirely on automatic mechanisms but has to recruit controlled processes as well.
      Furthermore, we found broad activation in the inferior parietal lobule, the
      prefrontal gyrus, pre-SMA and SMA and the cingulate cortex. This might reflect a
      strategic semantic search mechanism which probably can be illustrated with
      connectionist models of language processing. According to this, we hypothesize a
      neuroregulatory role for the thalamus and basal ganglia in regulating and
      monitoring the release of preformulated language segments for motor programming
      and semantic verification. According to our findings there is strong evidence,
      that especially the thalamus, the caudate nucleus, the cingulate cortex, the
      inferior parietal lobule and the prefrontal cortex are responsible for an
      accurate ambiguity resolution in the human brain.

PMID- 18061484
TI  - Tactile-associated recruitment of the cervical cord is altered in patients with
      multiple sclerosis.
AB  - Functional magnetic resonance imaging (fMRI) studies of the brain have shown that
      cortical reorganization might contribute to a more favourable clinical outcome of
      multiple sclerosis (MS). In order to assess whether fMRI changes can also be
      detected in the spinal cord from patients with MS, and to investigate their
      nature and extent, twenty-five patients and 12 matched healthy controls were
      scanned during a tactile stimulation of the palm of the right hand. The task
      related mean signal change was computed for all activated voxels within the
      cervical cord and, separately, in the right and left anterior, right and left
      posterior, and middle cervical cord from C5 to C8. Cord lesion number, brain T2
      weighted lesion load, gray matter mean diffusivity (MD), and normal appearing
      white matter MD and fractional anisotropy were also measured. One control and one
      patient were excluded prior to fMRI analysis due to motion artifacts. The task
      related signal change of all cord activated voxels was 3.2% (SD=0.8) for controls
      and 3.9% (SD=0.9) for MS patients (p=0.02). Compared with controls, MS patients
      showed a higher signal change in the following cord sections: right anterior at
      C5 (p=0.05), right anterior (p=0.04) and posterior (p=0.04) at C6, and middle at
      C6 (p=0.03) and C7/C8 (p=0.01). MS patients showed a more frequent cord activity
      in the left posterior cervical cord at C5/C6 than controls (p=0.02). No
      significant correlation was found between cord fMRI changes and brain structural
      MRI metrics. In MS patients, the over-recruitment of the ipsilateral posterior
      cervical cord associated to a reduced functional lateralization suggests an
      abnormal function of the spinal relay interneurons.

PMID- 18061485
TI  - Development of a predictive model for estimating the probability of treatment
      success one year after total shoulder replacement - cohort study.
AB  - OBJECTIVE: To Estimate the probability of treatment success 1 year after a total
      shoulder arthroplasty by developing a model based on preoperative clinical
      factors. METHOD: Between June 2003 and December 2006, 140 patients undergoing
      shoulder operations were assessed for age, gender, current rheumatoid arthritis,
      Short Form (SF) 36 physical and mental sum scores, previous shoulder operations,
      the Disabilities of Arm, Shoulder and Hand (DASH) symptom and function scores,
      the Shoulder Pain and Disability Index (SPADI), and insurance status. One year
      after the operation a Constant score of 80 or more out of 100 indicated
      successful treatment. Patient variables were analyzed with a logistic regression
      model augmented in a stepwise manner and bootstrapped 100 times. Variables
      selected at least 33 times were incorporated into a final model and the Area
      under the Receiver Operating Characteristics Curve (aROC) was calculated.
      RESULTS: There were 47/140 (33.6%) successful treatments. The probability of
      success was reduced in patients with previous shoulder operations (Odds Ratio
      [O.R.] 0.17, 95% Confidence Interval (95%CI) 0.04-0.85; P=0.03) and older than 75
      years (O.R. 0.21, 95%CI 0.05-0.77; P=0.02). The probability of success increased
      in patients with a higher SF 36 mental sum score (O.R. 1.03, 95%CI 0.96-1.09,
      P=0.42) and a higher DASH function score (O.R. 1.05, 95%CI 1.02-1.07, P=0.001).
      The aROC was 0.79 (0.70-0.88) indicating that the model has a high predictive
      capacity. CONCLUSION: Once validated this model based on four preoperative
      clinical factors offers a prediction of whether a patient will respond to
      treatment 1 year after total shoulder arthroplasty.

PMID- 18061486
TI  - One retrieval trial induces reconsolidation in an appetitive learning paradigm in
      honeybees (Apis mellifera).
AB  - Combining memory retrieval with the application of a protein synthesis-inhibitor
      leads to an amnestic effect that is referred to as the reconsolidation
      phenomenon. Several behavioural studies demonstrate that only a few or weak
      retrieval trials (that do not result in significant extinction) lead to this
      phenomenon. In contrast, many trials (that result in significant extinction)
      combined with a protein synthesis inhibitor result in an inhibition of the
      extinction memory. Based on these findings it was suggested that extinction is
      the boundary condition for reconsolidation: when extinction is induced the
      consolidation of the extinction memory is the dominant process. Recently we were
      not able to confirm this hypothesis in the honeybee (Apis mellifera): we did not
      find the reconsolidation phenomenon after one retrieval trial, but demonstrated
      reconsolidation after five retrieval trials that led to extinction. To exclude
      that this observation resembles a special case in insects we here wanted to know
      if one retrieval trial induces reconsolidation as it has been demonstrated before
      in many other species. To do so we used experimental parameters that had been
      used before to demonstrate consolidation in the honeybee with the exception that
      this time the protein synthesis-inhibitor was applied 1 h after one memory
      retrieval instead after acquisition. We thereby demonstrate the reconsolidation
      phenomenon after one retrieval trial but only when using the doubled dose of
      protein synthesis-inhibitor that has been used to inhibit consolidation.

PMID- 18061487
TI  - Growth and genetic responses of Salmonella Typhimurium to pH-shifts in an
      anaerobic continuous culture.
AB  - Salmonella infection of chickens that leads to potential human foodborne
      salmonellosis continues to be a concern. Changes in the pH of poultry
      gastrointestinal tract could influence Salmonella growth and virulence response.
      In the current study, growth responses of a chicken isolate Salmonella enterica
      serovar Typhimurium (ST) to three incremental pH-shifts (6.17-7.35) in continuous
      cultures (CC) were evaluated. The expression of rpoS and hilA was determined by
      real time-polymerase chain reaction (RT-PCR) as well. Increases in pH resulted in
      higher cell protein concentrations, glucose disappearance, and glucose and ATP
      yields. Although with some inconsistency between the two trials, the data
      indicated that the ammonia release into media was favored by low pH. The pH
      shifts did not significantly affect acetate biosynthesis. No consistent trends of
      pH influence on propionate and butyrate production could be detected. In all
      three pH shifts, relative expression of hilA was dominant at 0h which represented
      CC steady state. In pH shift 7.35-6.86 (Trial 1), the relative expression of rpoS
      at time 0 and 1h were over five-fold higher than after 3 and 6h of growth.
      Overall, the results suggest that ST physiology is altered by changes in pH,
      which could be determinant factors for ST survival in the poultry
      gastrointestinal ecosystems.

PMID- 18061488
TI  - Regarding "Luebke T, Aleksic M, Brunkwall J. Meta-analysis of randomized trials
      comparing carotid endarterectomy and endovascular treatment". Eur J Vasc Endovasc
      Surg 2007;34:470-479.

PMID- 18061489
TI  - Clinical and histomorphometric characteristics of three different families with
      hereditary gingival fibromatosis.
AB  - OBJECTIVE: To examine the histomorphologic and histomorphometric features of
      tissue from 3 unrelated families with hereditary gingival fibromatosis (HGF).
      STUDY DESIGN: Twelve affected individuals from 3 HGF families and 3 control
      subjects were evaluated. Gingival samples were fixed in formalin and embedded in
      paraffin for hematoxylin and eosin stain to count the number of fibroblast and
      inflammatory cells. Sirius red staining was performed to quantitate the amount of
      collagen present. RESULTS: Histomorphologic analysis of HGF showed extension of
      epithelial rete ridges into the underlying lamina propria and the presence of
      collagen bundles in the connective tissue. Analysis of the mean area fraction of
      collagen showed that there were significant increases in the collagen fraction
      for all HGF types compared with control subjects (P < .05). There were
      significant increases in the number of fibroblasts for HGFa and HGFb compared
      with control subjects (P < .05). The number of fibroblasts for HGFc were similar
      to that for control subjects. CONCLUSIONS: The collagen fraction was
      significantly greater in all HGF types compared with controls. The number of
      fibroblasts was significantly increased in 2 of the 3 HGF types compared with
      controls. These data indicate that different mechanisms may be responsible for
      tissue enlargement in different forms of HGF.

PMID- 18061490
TI  - Lymph node and pulmonary metastases after transplantation of oral squamous cell
      carcinoma cell line (HSC-3) into the subcutaneous tissue of nude mouse: detection
      of metastases by genetic methods using beta-globin and mutant p53 genes.
AB  - We attempted to establish an in vivo experimental model of metastasis of oral
      caner. The HSC-3 cell line, originating from human oral squamous cell carcinoma,
      was transplanted into nude mice, and metastases to the lymph node and the lung
      were investigated using genetic analysis. The HSC-3 cells, transplanted
      subcutaneously into the lateral back of nude mice, and punctured repeatedly after
      cyst formation, could metastasize to the lymph node and the lung. Genetic
      analysis using human beta-globin gene demonstrated that the frequency of
      metastasis to the lymph node and the lung at 12 weeks after the transplantation
      was 45% and 40%, respectively. Mutant allele-specific amplification of p53 gene
      could also detect micrometastasis with almost equal sensitivity of polymerase
      chain reaction with beta-globin gene. Subcutaneous transplantation is easy with
      excellent reproducibility compared with intravenous or orthotopic
      transplantation, and we think that this experimental model can be one of standard
      models of cancer metastasis.

PMID- 18061491
TI  - Comparative expression of RANK, RANKL, and OPG in keratocystic odontogenic
      tumors, ameloblastomas, and dentigerous cysts.
AB  - OBJECTIVE: The aim of this study was to compare the expression of nuclear factor
      kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in odontogenic
      epithelial tumors and dentigerous cysts. STUDY DESIGN: The expression of these
      molecules was evaluated in solid/multicystic ameloblastomas (n = 12) and
      unicystic ameloblastomas (n = 8), keratocystic odontogenic tumors (n = 19),
      dentigerous cysts (n = 9), and dental follicles (n = 9) by immunohistochemistry.
      RESULTS: In odontogenic epithelium, a similar expression of RANK, RANKL, and OPG
      was observed in all samples. With regard to stroma, the number of RANK-positive
      and RANKL-positive cells was higher in solid/multicystic ameloblastomas compared
      with dentigerous cysts. Dental follicles had lower numbers of RANK-positive,
      RANKL-positive, and OPG-positive cells than solid/multicystic ameloblastomas and
      keratocystic odontogenic tumors. The majority of solid/multicystic ameloblastomas
      (75%) and unicystic ameloblastomas (62.5%) had higher numbers of RANKL-positive
      than OPG-positive cells. In contrast, 62.4% of keratocystic odontogenic tumors
      and 100% of dentigerous cysts exhibited a higher content of OPG-positive than
      RANKL-positive cells. CONCLUSION: Our results indicate differences in the RANK,
      RANKL, and OPG expression in odontogenic epithelial tumors. The imbalance of
      these factors could contribute to the differential bone/tooth resorption activity
      in these lesions.

PMID- 18061492
TI  - Is there a role for arthrocentesis in recapturing the displaced disc in patients
      with closed lock of the temporomandibular joint?
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of
      arthrocentesis in releasing acute and chronic closed lock of the
      temporomandibular joint, improving function, reducing pain and recapturing the
      displaced disc. STUDY DESIGN: We performed arthrocentesis and mandibular
      manipulation (MM) as an initial treatment in 33 patients (unilateral involvement)
      with a variable duration of closed lock and magnetic resonance imaging (MRI)
      evidence of anterior disc displacement without reduction (ADDWR). Duration of
      locking ranged from 1 week to 2 years. After the procedure, soft diet,
      physiotherapy, and an interocclusal appliance (IA) were prescribed. Postoperative
      MRI images were obtained at 1 month. A clinical examination with analysis of
      maximal mouth opening (MMO), a visual analog scale (VAS), and a self-administered
      questionnaire were used for evaluation of pain, jaw dysfunction, and activities
      of daily living (ADL). The follow-up period was 1 year. RESULTS: At 1-year follow
      up, MMO had increased significantly from a mean of 24.7 +/- 5.9 mm to 39.6 +/-
      6.2 mm (P < .05). Functional improvement was associated with a significant
      reduction in VAS (from 6.2 +/- 2.3 to 2.8 +/- 3.4), pain (from 11.7 +/- 7.1 to 4
      +/- 3.8), dysfunction (from 8.6 +/- 4.9 to 3.2 +/- 2.8), and ADL scores (from
      13.9 +/- 12 to 4.4 +/- 5), with P < .05. The overall success rate was 72.7%; it
      was higher in acute patients (87.5%) than in chronic patients (68.0%). The disc
      was recaptured (the disc was interposed between the condyle and the eminence on
      closed and open MRI images) in 3 cases in which the duration of locking was less
      than 1 month (acute patients). CONCLUSIONS: The results indicate that
      arthrocentesis, in association with MM and IA, could be effective in improving
      function and reducing pain in patients with closed lock. Better results were
      obtained in terms of MMO, VAS, and questionnaire scores in acute closed lock
      cases than in chronic ones. Recapturing the anteriorly displaced disc is possible
      only in patients with acute closed lock.

PMID- 18061493
TI  - Orofacial manifestations of Robinow's syndrome: a case report in a pediatric
      patient.
AB  - Robinow's syndrome (Online Mendelian Inheritance in Man [OMIM] 268310), or fetal
      facies syndrome, is a rare genetic disorder causing autosomal dominant and
      recessive forms. This syndrome includes a series of anomalies such as short
      stature, characteristic facial dysmorphism (fetal facies), genital hypoplasia,
      and mesomelic brachymelia. The purpose of the present case is to describe the
      orofacial manifestations of the syndrome in a pediatric patient: craniofacial
      features, triangular mouth and a long upper lip philtrum, ankyloglossia, a
      shortened tongue devoid of tongue tip, a geographic tongue, arched palate,
      gingival hyperplasia, dental abnormalities (misaligned and crowded teeth), and
      delayed tooth eruption.

PMID- 18061494
TI  - Molecular cloning and characterization of WdTUP1, a gene that encodes a potential
      transcriptional repressor important for yeast-hyphal transitions in Wangiella
      (Exophiala) dermatitidis.
AB  - The general transcriptional repressor Tup1p is known to influence cell
      development in many fungi. To determine whether the Tup1p ortholog (WdTup1p) of
      Wangiella dermatitidis also influences cellular development in this melanized,
      polymorphic human pathogen, the gene (WdTUP1) that encodes this transcription
      factor was isolated, sequenced and disrupted. Phylogenetic analysis showed that
      the WdTup1p sequence was closely related to homologues in other polymorphic,
      conidiogenous fungi. Disruption of WdTUP1 produced mutants (wdtup1Delta) with
      pronounced growth and cellular abnormalities, including slow growth on various
      agar media and exclusively as a filamentous morphotype in liquid media. We
      concluded that WdTup1p represents an important switch regulator that controls the
      yeast-to-filamentous growth transition. However, detailed observations of the
      filamentous growth of the disruption mutant showed that the hyphae produced by
      the wdtup1Delta mutants, unlike those of the wild-type, were arrested at a stage
      prior to the formation of true hyphae and subsequent conidia production.

PMID- 18061496
TI  - Transverse and dorso-ventral changes in thoracic dimension during equine
      locomotion.
AB  - Changes in shape of the equine thorax during locomotion are not well defined,
      although it has been shown recently that the transverse hemi-diameter changes its
      dimension by up to 80mm on the side of the trailing forelimb during gallop,
      despite minimal change in thoracic circumference. The aim of this project was to
      analyse transverse and dorso-ventral changes in shape of the thorax
      simultaneously, and to determine if leading limb, treadmill slope and speed have
      an effect on these shape changes. Reflective markers were placed on the horse's
      hemi-thorax and movement of the markers was recorded using a motion capture
      system while the horse trotted and cantered on a treadmill. Treadmill speed and
      slope, and the lead the horse cantered on were varied to determine the effects
      these had on transverse hemi-diameter and dorso-ventral diameter. There was a
      negative correlation between transverse and dorso-ventral changes in thoracic
      dimension, the strength of which increased with speed on the trailing limb side.
      On the leading side, the relationship was either weakly negative or positive. The
      changes in dimension of the hemi-thorax were significantly greater on the
      trailing side compared to the leading side. Speed had small effects on thoracic
      shape changes, but inclined exercise caused an increase in transverse hemi
      diameter on the trailing side of the thorax. The changes in thoracic shape are
      unlikely to contribute substantially to ventilation and rib motion is likely to
      be due to protraction and retraction of the forelimbs. However, it may reflect
      asynchronous ventilation of lung lobes and partially explain the prevalence of
      exercise-induced pulmonary haemorrhage.

PMID- 18061495
TI  - Increased survival in dogs with malignant mammary tumours overexpressing HER-2
      protein and detection of a silent single nucleotide polymorphism in the canine
      HER-2 gene.
AB  - The aims of this study were to explore the relationship between clinical outcome
      and HER-2 protein expression in dogs with malignant mammary tumours after surgery
      and to determine the sequence of the HER-2 gene. Tissues from 91 dogs diagnosed
      with malignant mammary tumours, six with benign lesions and two normal mammary
      glands were analysed for the expression of HER-2 by immunohistochemistry (IHC).
      Exons 14-18 of the HER-2 gene were amplified by reverse transcriptase polymerase
      chain reaction and sequenced in 19 tumours with IHC scores >2+; larger coding
      regions of HER-2 were analysed in five tumours. HER-2 protein overexpression was
      found in 27/91 (29.7%) of canine malignant mammary tumours. Dogs with HER-2
      overexpressing malignant mammary tumours tended to have a higher survival rate
      than those that expressed a normal level of HER-2 within 2 years of surgery. In
      3/19 cases, HER-2 sequences had a single nucleotide polymorphism, T(1725)C, with
      no change in the amino acid identity (Cys). No other sequence aberration of HER-2
      was found.

PMID- 18061498
TI  - Wiring of the brain.

PMID- 18061497
TI  - Sub-aponeurotic fluid collections: a delayed-onset self-limiting cerebrospinal
      fluid fistula in young infants.
AB  - BACKGROUND: Transient sub-aponeurotic fluid collections are rarely recognized
      lesions that may be frequently related to traumatic labor and occur within weeks
      after birth. Their etiology has remained uncertain. METHODS AND RESULTS: Here we
      report on five new cases with typical clinical findings and normal neuroimaging.
      A detailed analysis of the lesion aspirates was performed in three patients,
      always revealing beta(2)-transferrin and high concentrations of beta-trace
      protein. CONCLUSIONS: This indicates that cerebrospinal fluid leakage contributes
      to this rare condition. All lesions disappeared spontaneously within 2-5 months
      so that conservative treatment seems appropriate.

PMID- 18061499
TI  - Diffusion tensor imaging in infants with basal ganglia-thalamic lesions.
AB  - We performed diffusion tensor imaging in two infants with neonatal hypoxic
      ischemic encephalopathy. MRI revealed basal ganglia-thalamic lesions in both
      patients during the neonatal period. Patient 1 had severe neurological sequelae,
      whereas patient 2 achieved normal development. Conventional MRI at 12 months of
      age showed abnormal high-intensity areas in bilateral basal ganglia and thalami
      in patient 1, whereas no abnormal intensities were recognized in patient 2.
      Diffusion tensor tractography demonstrated poor depiction of white matter tracts
      above the level of centrum semiovale in patient 1. Region of interest analysis
      showed that fractional anisotropy of white matter of centrum semiovale and deep
      white matter was markedly reduced in patient 1 compared with patient 2, although
      apparent diffusion coefficient was not largely different between them. Our study
      suggested that abnormalities of diffusion property will be more widely present
      than those of conventional MRI. Diffusion tensor imaging will be useful to detect
      white matter abnormalities in normal-appearing white matter on conventional MRI.

PMID- 18061500
TI  - Identification of ligand features essential for HDACs inhibitors by pharmacophore
      modeling.
AB  - Histone deacetylases (HDACs) enzyme plays a significant role in transcriptional
      regulation by modifying the core histones of the nucleosome. It has emerged as an
      important therapeutic target for the treatment of cancer and other diseases.
      Inhibitors of HDACs become a new class of anticancer agents and have provoked
      much interest amongst pharmacologists and cancer researchers. To facilitate the
      discovery of specific HDACs inhibitors, a 3D chemical-feature-based QSAR
      pharmacophore model was developed and was well consistent with the structure
      functional requirements for the binding of the HDAC inhibitors. Using this model,
      the interactions between the benzamide MS-275 and HDAC were explored. The result
      showed that the type and spatial location of chemical features encoded in the
      pharmacophore are in full agreement with the enzyme-inhibitor interaction pattern
      identified from molecular docking.

PMID- 18061501
TI  - The present status of medical physics education and training in Europe: an EFOMP
      survey.
AB  - The aim of this work is to present the results of an EFOMP's survey on the status
      of Education and Training of Medical Physics in Europe. This survey has been
      undertaken by EFOMP in 2005, to update the document "Policy Statement No. 1",
      which represents the starting point of the EFOMP recommendations on Education and
      Training in Medical Physics. Ultimate results have been collected at the end of
      2006. To perform the survey, a questionnaire was sent to 34 National Member
      Organisations (NMOs) for Medical Physics, to collect information on the present
      state of education and training in each European country. Twenty-five countries
      participated in the enquiry and responded to it. The most outstanding results are
      as follows: In all countries, the basic requirement to enter the Medical Physics
      education is a university degree. The length of this university education ranges
      from 2 to 5 years. Concerning the Post-graduate education in Medical Physics: A
      nationally approved educational programme is in operation in 16 of the 25
      countries. Postgraduate education takes place essentially within 3 different
      approaches and the total length of Medical Physics education and training ranges
      from 2 1/2 years to 9 years. In 14 countries, it is mandatory to hold a diploma
      or license to work as a Medical Physicist. It allows working in all areas of
      competence (the most mentioned were Radiotherapy, Nuclear Medicine, Diagnostic
      Radiology and Radiation Protection) in 14 countries, whereas in 4 countries it
      allows to work only in 1 or 2 areas. Seventeen countries have a register for
      Medical Physicists. A formal CPD (Continuing Professional Development) programme
      is in operation in 13 countries.

PMID- 18061502
TI  - [The first ray of the hand and the foot of the primates (I). Descriptive
      anatomy].
AB  - Dissection of the first ray and the connecting structures of the hand and the
      foot of simian primates, conserved by freezing or embalming and observation of
      325 skeletal pieces of specimens of the Museum of Natural History of Paris. The
      trapezometacarpal articulation is a saddle joint with a trapezial concavity
      according to its great oblique axis directed at 45 degrees with respect to a
      sagittal plan for the whole of the simian primates, with a trapezoidal concavity
      according to a great axis directed in a sagittal plan for the loridae, the
      galagonidae and the daubentonidae and with a counter fort supported by a
      mediopalmar apophysis or a sesamoid bone for the lemurpides. The whole of the
      mediopalmar ligaments is inserted distally on the medial tubercle at the basis of
      the first metacarpus. This insertion was fibrocartilaginous for the gorilla. The
      mediopalmar ligaments are very more developed than the laterodorsal ligaments in
      all the hominidae and the catarhinious. The both groups are equivalent for the
      platyrhinious and the prosimious. An intracapsular ligament may reinforce the
      laterodorsal by the lemoridae. The cuneometatarsal articulation presents a
      sagittal great axis. It was in fact a spiral trochoid joint with a cuneiform
      convexity in all the simian primates except for the humans. In this late case,
      the articular surface was less high, more narrow, with less marked relief. The
      form of this articulation is that of a saddle with a sagittal concavity in the
      prosimious with a strong lateral and palmar cuneiform tuberosity and a big
      lateral opposite apophysis at the basis of the first metatarsus. The tendon of
      the long lateral fibular muscle and one fascicle of the tendon of the anterior
      tibialis is fixed on the both side of the basis of the first metatarsus, except
      for human beings in which the tendon was undivided and was principally inserted
      of the navicular bone. The disposition of the cuneometatarsal ligaments is
      similar to that of the trapezometacarpal ligaments. The distal insertions of the
      lateral ligaments are fibrocarlilaginous in the cerpopithecidae. All the
      metacarpophalangeal and metatarsophalangeal are condylar, except for the
      metacarpophalangeal of the humans which looks like bicondylar; the
      interphalangeal articulations are bicondylar. The ligamentous devices include the
      glenoidal and collateral ligaments with their metacarpal- and metatarsophalangeal
      fascicles and their interphalangeal and phalangeoglenoidal fascicles.

PMID- 18061506
TI  - [Development and validation of a dynamic model of the knee].
AB  - The authors report the methodology of the construction of a multibody model of
      the knee and the validation of the kinematics of the modelled knee. The
      construction of the model includes: the rigid bodies represented by osseous
      components (femur, tibia, fibula, patella), the ligamentous structures
      (collateral ligaments, patellar ligament, cruciates ligaments), the muscular part
      represented by the quadriceps. Morphological data were acquired through 3D CT
      scans for the bones and a biometrical study of the ligaments (insertions,
      orientation, length, section). Ligament biomechanics was modelled as bilinear
      springs (in compression the tightness is null; in traction it is a function of
      length, section and Young modulus of elasticity). The quadriceps was modelled as
      a sliding channel with a translatory servocommand. Contacts at the interfaces
      (femur/patella; femur/tibia) were evaluated according to the index of penetration
      (distance D) between two bodies where effort was: Dx10(5) N/mm(2)). The model was
      tested simulating a symmetrical kneeling (800 N body weight) and required a
      ground link modelled as a ball and socket joint. The model was developed under
      ADAMS software. The validation of the kinematics of the modelled knee was
      provided according to the data of Wilson et al. who have shown that (i) in normal
      knees, internal/external rotation, abduction/adduction and all three components
      of translation are coupled to flexion angle both in passive flexion and
      extension; (ii) the tibia rotates internally as the knee is flexed. The
      consistency of the coupled motions support the model's premise that passive knee
      motion is guided by isometric fascicles in anterior and posterior cruciates, by
      the medial collateral ligament and by articular contact in the medial and lateral
      compartments. The main curves (internal/external rotations; posterior/anterior
      translation) of the model conforms with the framework of Wilson.

PMID- 18061507
TI  - [How I do... Bartholin gland cystectomy].

PMID- 18061508
TI  - Assessment of an ultrasonic dermal scanner for skin thickness measurements.
AB  - The measurement precision of a 20 MHz ultrasound dermal scanning system, Episcan,
      manufactured by Longport Inc. was investigated for its use in the measurement of
      skin thickness. Results from measurements of relatively ideal homogeneous,
      uniformly thick plastic plates indicate that the scanner can accurately measure
      to depths of 8-34 mm from the surface of the transducer or approximately 18 mm
      from the surface of the latex probe-cover with a high level of precision, less
      than 1% of the mean thickness. The precision was determined to be dependent on
      the depth of the scan. Using the measured optimal gain of 45%, a sample rate of
      0.013 micros, and an A-scan record length of 1024 points, we determined the
      thickness resolution of the device is on the order of 0.003 mm for 2 mm thick
      layers and 0.01 mm for 5 mm thick layers. We conclude that variations greater
      than this value for clinical dermal thickness measurements are not due to
      instrument precision, but must result from the limitations of analyzing the data
      from real tissue.

PMID- 18061509
TI  - How the Smads regulate transcription.
AB  - The primary signalling pathway downstream of ligands of the transforming growth
      factor beta (TGF-beta) superfamily is the Smad pathway. Activated receptors
      phosphorylate receptor-regulated Smads, which form homomeric complexes and
      heteromeric complexes with Smad4. These activated Smad complexes accumulate in
      the nucleus, where they are directly involved in the regulation of transcription
      of target genes. This apparently very simple pathway is subject to complex
      regulation, much of which is at the level of post-translational modifications of
      pathway components, in particular, the Smads. The enzymes responsible may be
      constitutively active, may be cell type-specific or may be regulated by other
      signalling pathways or by the cell cycle. In this way, signals from TGF-beta
      superfamily ligands are integrated with signals from other growth factors and
      cytokines, are regulated by the cell cycle and are dependent on cell type. This
      may go some way to explaining the pleiotropic nature of TGF-beta superfamily
      responses. In this review we focus on the mechanisms whereby the Smads are
      modified and regulated. We then go on to discuss how the activated Smad complexes
      regulate transcription.

PMID- 18061510
TI  - Leishmania mitochondrial tRNA importers.
AB  - The RNA Import Complex (RIC) is a multi-subunit protein complex from the
      mitochondria of the kinetoplastid protozoon Leishmania tropica that induces
      transport of tRNA across natural and artificial membranes. Leishmania,
      Trypanosoma and related genera of the order Kinetoplastidae are early diverging,
      atypical eukaryotes with unique RNA metabolic pathways, including the import of
      nucleus-encoded tRNAs into the mitochondrion to complement the deletion of all
      organelle-encoded tRNA genes. Biochemical and genetic studies of RIC are
      contributing to greater understanding of the mechanism of import. Additionally,
      RIC was shown to act as an efficient delivery vehicle for tRNA and other small
      RNAs into mitochondria within intact mammalian cells, indicating its
      applicability to the management of diseases caused by mitochondrial mutations.

PMID- 18061511
TI  - The Agrobacterium tumefaciens DnaK: ATPase cycle, oligomeric state and chaperone
      properties.
AB  - DnaK is a molecular chaperone that promotes cell survival during stress by
      preventing protein misfolding. The chaperone activity is regulated by nucleotide
      binding and hydrolysis events in the N-terminal ATPase domain, which in turn
      mediate substrate binding and release in the C-terminal substrate binding domain.
      In this study we determined that ATP hydrolysis was the rate limiting step in the
      ATPase cycle of Agrobacterium tumefaciens DnaK (Agt DnaK); however the data
      suggested that Agt DnaK had a significantly lower affinity for ATP than
      Escherichia coli DnaK. We show for the first time that Agt DnaK was very
      effective at preventing thermal aggregation of malate dehydrogenase (MDH) in a
      concentration dependent manner. This is in contrast to E. coli DnaK which was
      ineffective at preventing thermal aggregation of MDH. A mutant Agt DnaK-V431F,
      with a blocked hydrophobic pocket in the substrate binding domain, was unable to
      suppress the thermosensitivty of an E. coli dnaK103 deletion strain. However the
      mutation did not inhibit Agt DnaK-V431F from preventing the thermal aggregation
      of MDH. The oligomeric state of Agt DnaK was studied using size exclusion
      chromatography. We demonstrated that dilution of the Agt DnaK protein, the
      addition of ATP and the removal of the 10kDa C-terminal alpha-helical subdomain
      reduced higher order associations but did not abrogate dimerisation. Our research
      implies that the C-terminal alpha-helical subdomain is involved in higher order
      associations, while the substrate binding domain is possibly involved in
      dimerisation.

PMID- 18061513
TI  - Tumor-induced modulation of dendritic cell function.
AB  - Dendritic cells (DC) are specialized antigen presenting cells that acquire,
      process, and present tumor-associated antigens to T cells for the induction of
      antigen-specific tumor immune responses. DC have been shown to infiltrate many
      tumors but both, circulating and tumor-infiltrating DC from cancer patients,
      appear to be phenotypically and functionally defective. Several tumor-derived
      factors such as VEGF, IL-6, IL-10, M-CSF, and STAT-3 have been shown to be
      responsible for systemic and local DC defects. Furthermore, tumor metabolites
      such as lactic acid may also critically contribute to DC dysfunction and tumor
      immune escape. The correction of abnormal DC function might be a requirement for
      successful vaccine approaches against cancer.

PMID- 18061512
TI  - Genetic and epigenetic alterations in breast cancer: what are the perspectives
      for clinical practice?
AB  - The worldwide incidence of breast cancer affects 1.2 million women each year. In
      contrast to the high occurrence of this malady, a decline in mortality is
      reported among industrialized countries. In this respect, both awareness
      campaigns and substantial progress achieved in therapy and diagnosis allowed for
      the enhancement of the survival rate in patients with breast cancer. Undoubtedly,
      oncology research programs played a relevant role in the improvement of
      therapeutics and diagnostics for breast cancer. Major strides were reported,
      especially over the last decade and a half, in better understanding molecular and
      cellular biology events involved in breast cancer pathogenesis and progression of
      the disease. However, therapeutic approaches for the treatment of patients with
      breast cancer need further improvement. Therapeutic interventions can chronically
      compromise both the state of health and quality of life of breast cancer
      survivors. In addition, current therapeutic approaches have not significantly
      improved the survival rate in patients with metastatic disease. On these grounds,
      it is necessary to develop more efficient therapeutics and diagnostic tools,
      which can improve the health and quality of life of breast cancer survivors and
      increase the survival rate in patients with metastatic disease. In this respect,
      the field of cancer research has placed a particular emphasis on the elucidation
      of genetic and epigenetic alterations that may lead to the pathogenesis of breast
      cancer and contribute to its progression.

PMID- 18061514
TI  - The real challenge to free will and responsibility.

PMID- 18061515
TI  - Dupoux and Jacob's moral instincts: throwing out the baby, the bathwater and the
      bathtub.

PMID- 18061516
TI  - Repeatability and reliability of ocular aberration measurements in contact lens
      wear.
AB  - BACKGROUND: To assess repeatability and within- and between-observer reliability
      when measuring ocular aberrations with and without soft contact lens wear.
      METHODS: The irx3 aberrometer was used to measure second to tenth radial order
      aberrations on 13 subjects with and without their habitual soft contact lenses.
      This was first performed by one observer, who took three separate measurements to
      determine repeatability. In addition, two observers each took a set of three
      measurements on two occasions, to determine within- and between-observer
      reliability. Data were normalized to a constant pupil size for all measurements
      made on each subject. RESULTS: There was no difference in repeatability with or
      without contact lenses for Zernike polynomial numbers 3-20. There was no
      difference between within- and between-observer relative reliability either with
      lenses (t=1.9, p=0.07) or without lenses (t=1.1, p=0.29). However, both within
      observer and between-observer reliability were worse when lenses were worn
      (t=3.6, p=0.0009 and t=2.8, p=0.0074, respectively). CONCLUSION: The reduction in
      within- and between-observer reliability when measuring aberrations in contact
      lens wearers may be due to variability resulting from a variety of factors, such
      as lens flexure, lens movement, lens decentration and reduced stability of the
      pre-lens tear film.

PMID- 18061517
TI  - In the bag IOL dislocation following uncomplicated phacoemulsification.
AB  - We present two cases of early post-operative, in the bag intraocular lens (IOL)
      dislocation following uncomplicated phacoemulsification. Dislocation occurred in
      the presence of capsular fibrosis and anterior capsular phimosis. One patient was
      a known diabetic, the other diagnosed with pseudoexfoliation syndrome. These are
      recognised risk factors for capsular fibrosis. Surgical management included
      enlargement of the anterior capsular opening using intraocular micro-scissors and
      vitreous cutter to facilitate the removal of the dislocated IOL from the capsular
      bag. Both patients achieved a satisfactory visual outcome following IOL exchange
      with a rigid, sulcus fixated posterior chamber IOL (PCIOL). We discuss the risk
      factors for capsular fibrosis and propose preventative strategies to reduce the
      incidence of in the bag IOL dislocation.

PMID- 18061518
TI  - Nasopharyngeal carcinoma: current management, future directions and dental
      implications.
AB  - Nasopharyngeal carcinoma (NPC) is a distinct cancer of the head and neck.
      Approximately 70% of patients with NPC present with locally advanced disease.
      Phase III clinical trials support combined chemotherapy and radiotherapy for the
      initial treatment of these patients. Current treatment approaches for metastatic
      disease are variable. Oral complications of therapy for NPC are very common. In
      order to support cancer therapy the dental provider must be aware of the
      diagnosis, prognosis and approach to treatment. Dental care requires that
      radiation fields be understood as well as the permanent changes that occur with
      high dose radiation therapy. Radiation causes changes in bone and soft tissue
      that may result in acute and chronic oral complications. The most common acute
      complications are mucositis, infection, xerostomia and taste changes. Mucositis
      is of increased severity and duration when chemotherapy is combined with
      radiation therapy. Chronic complications are due to late effects of radiation
      therapy including hyposalivation, infection, taste change, dysphagia and trismus.
      Treatment innovations with molecularly targeted therapies and immunotherapy are
      being assessed to improve treatment outcomes in NPC and will impact oral
      complications and oral care.

PMID- 18061519
TI  - Induction chemotherapy followed by alternating chemo-radiotherapy in non-endemic
      undifferentiated carcinoma of the nasopharynx: optimal compliance and promising 4
      year results.
AB  - Concomitant chemo-radiotherapy is the standard treatment for advanced
      nasopharyngeal carcinoma (NPC). Induction chemotherapy may improve the results
      further by enhancing both loco-regional and distant control. Fifty patients with
      untreated, stage IV (UICC 1992) undifferentiated NPC were initially treated with
      three courses of epidoxorubicin, 90 mg/m(2), day 1 and cisplatin, 40 mg/m(2),
      days 1 and 2, every three weeks and then underwent three courses of cisplatin, 20
      mg/m(2)/day, days 1-4 and fluorouracil, 200mg/m(2)/day, days 1-4 (weeks 1, 4, 7),
      alternated to three splits of radiation (week 2-3, 5-6, 8-9-10) up to 70 Gy. All
      patients but one received 3 cycles of induction chemotherapy. Toxicities from
      induction chemotherapy were grade III or IV mucositis (2%), grade III or IV
      nausea/vomiting (22%), grade III or IV hematological toxicity (6%). At the end of
      induction phase 12% of CRs, 84% of PRs were recorded. Toxicities from alternating
      chemo-radiotherapy were grade III or IV mucositis (30%), grade III or IV
      nausea/vomiting (8%), grade III or IV hematological toxicity (24%). Overall, 86%
      of CRs and 14% of PRs were observed. Four-year progression free survival and
      overall survival rates are 71% and 81%, respectively. In a small number of
      patients studied, no correlation between the level of EGFR overexpression and
      outcomes was detected. In locally advanced UNPC our combined program including
      induction chemotherapy followed by alternating chemo-radiotherapy is active and
      gives promising long-term outcomes with acceptable toxicity and optimal patients'
      compliance. This program merits to be tested in a phase III trial.

PMID- 18061520
TI  - Oral proliferative verrucous leukoplakia revisited.

PMID- 18061521
TI  - The enamel matrix derivative (Emdogain) enhances human tongue carcinoma cells
      gelatinase production, migration and metastasis formation.
AB  - Enamel matrix derivative Emdogain (EMD) is widely used in periodontal treatment
      to regenerate lost connective tissue and to improve the attachment of the teeth.
      Gelatinases (MMP-2 and -9) have an essential role in the promotion and
      progression of oral cancer growth and metastasis formation. We studied the
      effects of EMD on human tongue squamous cell carcinoma (HSC-3) cells in vitro and
      in vivo. In vitro, EMD (100 microg/ml and 200 microg/ml) remarkably induced the
      MMP-2 and -9 production from HSC-3 cells analysed by zymography and enzyme-linked
      immunosorbent assay. EMD also slightly induced the MMP-2 and -9 production from
      benign human mucosal keratinocytes (HMK). Furthermore, EMD clearly induced the
      transmigration of HSC-3 cells but had no effect on the HMK migration in transwell
      assays. The in vitro wound closure of HSC-3 cells was notably accelerated by EMD,
      whereas it had only minor effect on the wound closure of HMKs. The migration of
      both cell lines was inhibited by a selective cyclic anti-gelatinolytic peptide
      CTT-2. EMD had no effect on HSC-3 cell proliferation or apoptosis and only a
      limited effect on cell attachment to various extracellular matrix components. The
      in vivo mice experiment revealed that EMD substantially induced HSC-3 xenograft
      metastasis formation. Our results suggest that the use of EMD for patients with
      oral mucosal carcinomas or premalignant lesions should be carefully considered,
      possibly avoided.

PMID- 18061522
TI  - Salivary mRNA targets for cancer diagnostics.
AB  - Head and neck squamous cell carcinoma (HNSCC) affects almost 1 million people
      worldwide per year. Despite therapeutic advances the overall survival rate
      remains low because diagnosis often occurs only at advanced stages with poor
      prognosis. Like in most cancers, the implementation of an early detection scheme
      would have a positive impact on this disease. Similarly, as oral cancer has a
      very high recurrence rate, the early identification of recurrence or second
      primary tumors is an important challenge. HNSCC detection is currently based on
      expert clinical examination of the upper aerodigestive tract and histologic
      analysis of suspicious areas, but it may be undetectable in hidden sites, and
      unfortunately visual screening for oral lesions is an often neglected part of
      dental healthcare. Our group is actively pursuing the assembly of a toolbox for
      the molecular analysis of oral fluid. Here we present our current status
      utilizing the salivary transcriptome for oral cancer diagnostics.

PMID- 18061523
TI  - HPV16 transmission between a couple with HPV-related head and neck cancer.
AB  - Although squamous cell carcinoma of the head and neck (SCCHN) is closely linked
      to tobacco and alcohol use, there is an increasing incidence HPV16-related SCCHN
      arising in the oropharynx. The mechanisms of viral transmission, carcinogenesis
      and natural history are not well understood. Here, we report a couple-husband and
      wife diagnosed synchronously with squamous cell carcinoma of the head and neck
      wherein the tumors were positive for HPV16 by PCR diagnosis. Both viral genomes
      were genetically identical and closely related to the revised European prototype,
      HPV16R. An uncommon signal variant nucleotide was identified in both genomes that
      is not present in the HPV16R. These tumors likely represent transmission between
      the couple.

PMID- 18061524
TI  - Overexpression of COX-2 and LMP1 are correlated with lymph node in Tunisian NPC
      patients.
AB  - Cyclooxygenase 2 (COX-2) an inducible form of COX is frequently up-regulated in
      many human tumours. The expression of COX-2 in nasopharyngeal carcinoma (NPC) and
      its relationship to clinicopathological features were studied in Tunisian
      patients. COX-2 mRNA was detected in 91% of tumour tissues. Immunohistochemical
      analysis showed that COX-2 protein was strongly detected in tumour cells and the
      staining was mainly cytoplasmic. In contrast, COX-2 mRNA and protein were very
      low or undetectable in normal nasopharyngeal mucosa. Our result showed a
      significant association of COX-2 overexpression with the lymph node involvement,
      however, no correlation was observed with age, tumour stage, histological type
      and distant metastasis. Moreover, we showed that all tumour specimens co
      overexpressed COX-2 and the EBV oncoprotein LMP1 corroborating the fact that LPM1
      is known to induce COX-2. Altogether, our data suggests that the COX-2 is
      overexpressed in NPC biopsies and that is linked to the lymph node involvement.

PMID- 18061525
TI  - Expression of RCAS1 is significantly associated with the progression and
      prognosis of oral squamous cell carcinomas in Taiwan.
AB  - This study used an immunohistochemical technique to examine the expression of
      receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in 84 specimens
      of oral squamous cell carcinoma (OSCC), 106 specimens of oral epithelial
      dysplasia (OED, 32 mild, 44 moderate, and 30 severe OED cases), and 20 specimens
      of normal oral mucosa (NOM). We found that the mean RCAS1 labeling indices (LIs)
      increased significantly from NOM (12+/-5%) through mild OED (31+/-13%), moderate
      OED (44+/-17%), and severe OED (56+/-18%) to OSCC samples (68+/-20%, p<0.001). A
      significant correlation was found between the higher mean RCAS1 LI and OSCCs with
      larger tumor size (p=0.001), positive lymph node metastasis (p<0.001), or more
      advanced clinical stages (p<0.001). Positive lymph node metastasis (p=0.0073) and
      RCAS1 LI > or = 60% (p=0.048) were identified as independent unfavorable
      prognosis factors by multivariate analyses with Cox regression model. Kaplan
      Meier curve showed that OSCC patients with a RCAS1 LI > ot = 60% had a
      significantly poorer cumulative survival than those with a RCAS1 LI<60% (log-rank
      test, p=0.0113). We conclude that the expression of RCAS1 is an early event in
      oral carcinogenesis. The RCAS1 LI in OSCC samples can predict the progression of
      OSCCs and the survival of OSCC patients.

PMID- 18061526
TI  - CCND1 polymorphisms (A870G and C1722G) modulate its protein expression and
      survival in oral carcinoma.
AB  - Cyclin D1 is an essential regulator of the G1 phase of the cell cycle progression
      and plays an important role in the transition of the cell from the G1 phase to
      the S phase of the cell cycle. Overexpression of cyclin D1 is a frequently
      observed feature of human cancers of diverse histological origin. Recently, we
      have reported overexpression of cyclin D1 in oral carcinoma. However, the
      underlying mechanism leading to this aberrant expression remains poorly
      understood. In this study, we have investigated the role of CCND1 A870G and
      C1722G polymorphisms on cyclin D1 expression and prognosis in a relatively
      homogenous population of 178 oral squamous cell carcinoma patients by PCR-SSCP,
      RFLP, RT-PCR and immunohistochemical methods. Genotype frequencies of both the
      polymorphisms were conformed to Hardy-Weinberg equilibrium. CCND1 A870G (p=0.004)
      and C1722G (p=0.012) polymorphisms were significantly associated with cyclin D1
      expression. Kaplan-Meier estimates revealed that CCND1 genotypes A870G 'GG'
      (p=0.012) and C1722G 'CC' (p=0.021) could predict the poor survival of the
      patients. In multivariate analysis, CCND1 A870G genotype combination (p=0.024, HR
      - 1.74 (1.08-2.81)) and cyclin D1 expression (p=0.025, HR - 1.72 (1.07-2.77))
      were independent predictors of survival in this patient cohort. Our results thus
      demonstrate, CCND1 polymorphisms stand-in as cis-acting regulatory elements
      modulating its expression and cyclin D1 genotype and phenotype could provide
      valuable additional information regarding prognosis of oral cancer patients.

PMID- 18061527
TI  - Metastatic tumours to the oral cavity - pathogenesis and analysis of 673 cases.
AB  - The oral region is an uncommon site for metastatic tumour cell colonization and
      is usually evidence of a wide spread disease. In 25% of cases, oral metastases
      were found to be the first sign of the metastatic spread and in 23% it was the
      first indication of an undiscovered malignancy at a distant site. The jawbones,
      particularly the mandible, were more frequently affected than the oral soft
      tissues (2:1). In the oral soft tissues, the attached gingiva was the most
      commonly affected site (54%). The major primary sites presenting oral metastases
      were the lung, kidney, liver, and prostate for men, breast, female genital organs
      (FGO), kidney, and colo-rectum for women. The primary site differs according to
      oral site colonization, in men the lung was the most common primary site
      affecting both the jawbones and oral mucosa (22% and 31.3%, respectively)
      followed by the prostate gland in the jawbones (11%) and kidney in the oral soft
      tissues (14%). In women, the breast was the most common primary tumour affecting
      the jawbones and soft tissues (41% and 24.3%, respectively), followed by the
      adrenal and female genital organs (FGO) in the jawbones (7.7%) and FGO in the
      soft tissues (14.8%). The clinical presentation of the metastatic lesions differ
      between the various sites in the oral region. In the jawbones most patients
      complain of swelling, pain and paresthesia which developed in a relative short
      period. Early manifestation of the gingival metastases resembled a hyperplastic
      or reactive lesion, such as pyogenic granuloma, peripheral giant cell granuloma,
      or fibrous epulis. Because of its rarity, the diagnosis of a metastatic lesion in
      the oral region is challenging, both to the clinician and to the pathologist, in
      recognizing that a lesion is metastatic and in determining the site of origin.
      The clinical presentation of a metastatic lesion in the oral cavity can be
      deceiving leading to a misdiagnosis of a benign process, therefore, in any case
      where the clinical presentation is unusual especially in patients with a known
      malignant disease a biopsy is mandatory.

PMID- 18061528
TI  - Prospective phase II trial of concomitant boost radiotherapy for stage II
      nasopharyngeal carcinoma.
AB  - Stage II nasopharyngeal carcinoma (NPC) treated with conventionally fractionated
      radiotherapy results in suboptimal outcome. This report aims to document the
      outcome of Stage II NPC patients treated with external beam radiotherapy
      delivered using an accelerated concomitant boost (C-Boost) schedule. Forty-seven
      1997 AJCC Stage II NPC patients were enrolled and analyzed in this prospective
      phase II clinical trial. The primary tumor and clinically involved nodes received
      a total dose of 72Gy in 42 fractions. C-Boost for gross disease consisted of 18Gy
      in 12 fractions commencing on day 19, and delivered at least 6h after the first
      dose. Patients were assessed for response, survival and toxicity. With a median
      follow-up of 30 months, 4 patients developed local recurrence only, 2 had
      persistent neck nodal disease or recurrence, and 1 with both locoregional
      recurrences. Distant metastases were seen in 5 patients, with or without
      locoregional recurrence. A total of 5 patients succumbed from nasopharyngeal
      cancer: four from effects of distant metastases and 1 from progressive local
      disease. The 3-year local, regional, and overall survival rates were 87.1%, 92%,
      and 85.9%, respectively. All patients experienced some degree of acute and/or
      late toxicity. Moderate to severe late toxicities (grade 3 and 4) were observed
      in 17% of cases. This C-Boost radiotherapy regimen administers a higher
      biologically effective dose compared with conventional radiation schedules. The
      local control after C-Boost radiation seems high for patients with stage II
      nasopharyngeal carcinoma, thus justifies further investigation to confirm its
      efficacy.

PMID- 18061529
TI  - Correlation between c-Jun and human papillomavirus in oral premalignant and
      malignant lesions.
AB  - c-Jun, one of the components of the transcription factor activating protein-1 (AP
      1), is suggested as a factor in malignant progression of oral lesions. c-Jun and
      other AP-1 components relationships with human papillomavirus (HPV) infection
      have been investigated, but not yet focusing on oral carcinogenesis. The aim of
      this study was to verify whether c-Jun immunohistochemical expression is related
      to HPV DNA detection in oral premalignant and malignant lesions. Fifty cases
      diagnosed as oral leukoplakias, with different degrees of epithelial dysplasia,
      and as oral squamous cell carcinomas (OSCC) were submitted to
      immunohistochemistry to detect c-Jun and to in situ hybridization with signal
      amplification to assess HPV DNA. It was verified that c-Jun nuclear expression
      increased according to the degree of dysplasia within the lesion, with the
      greatest expression in OSCC. The same did not happen concerning HPV infection--a
      discrete proportional relation was observed in indexes found in leukoplakia with
      no dysplasia, leukoplakia with dysplasia and OSCC, but statistically
      insignificant. When separating the group of leukoplakia by degrees of dysplasia,
      this relation of proportion was not observed. Nevertheless, the overall
      prevalence of HPV infection was 24% and the high-risk HPV types were the most
      frequently identified, which does not allow excluding HPV as a risk factor in
      oral carcinogenesis. When relating c-Jun expression and HPV infection, no
      statistically significant relationship is observed. Results suggest then that
      malignant progression mediated by c-Jun is independent of the presence of HPV in
      oral carcinogenesis.

PMID- 18061530
TI  - Molecular alterations in the tumor suppressor gene WWOX in oral leukoplakias.
AB  - Oral leukoplakia is the most prevalent and potentially malignant disorder of the
      oral mucosa. Previous studies have demonstrated that molecular changes of the
      WWOX gene (WW-domain containing oxidoreductase), a candidate tumor suppressor
      gene located at 16q23.3-24.1 that spans FRA16D, the second most common fragile
      site, are present in several malignant neoplasias, including oral squamous cell
      carcinoma. In this report, the role of the WWOX gene was investigated in 23 cases
      of oral leukoplakias. Using nested RT-PCR and immunohistochemistry, altered mRNA
      transcription and/or reduced Wwox protein expression was observed in 35% of the
      lesions when compared with normal mucosa. The majority of lesions (4/6) with
      altered transcripts had a reduction in the expression of Wwox protein. Although
      normal WWOX expression was found in some lesions with dysplasia, all lesions with
      WWOX mRNA and/or protein expression showed histological evidence of dysplasia and
      none of the cases without dysplasia presented this alteration. These results show
      that the WWOX gene alteration is an early genetic alteration and may contribute
      to oral carcinogenesis.

PMID- 18061531
TI  - The hamster model of sequential oral oncogenesis.
AB  - Oral squamous cell carcinoma (OSCC) is a common cancer characterised by low
      survival rate and poor prognosis. The multistep process of oral carcinogenesis is
      affected by multiple genetic events such as alterations of oncogenes and tumour
      suppressor genes. The use of appropriate experimental animal models that
      accurately represent the cellular and molecular changes which are associated with
      the initiation and progression of human oral cancer is of crucial importance. The
      Syrian golden hamster cheek pouch oral carcinogenesis model is the best known
      animal system that closely correlates events involved in the development of
      premalignant and malignant human oral cancers. Therefore, we established an
      experimental system of chemically induced oral carcinogenesis in hamsters, in
      order to study different stages of tumour formation: normal mucosa,
      hyperkeratosis, hyperplasia, dysplasia, early invasion, well differentiated OSCC
      and moderately differentiated OSCC. We investigated the expression of oncogenes
      EGFR, erbB2, erbB3, FGFR-2, FGFR-3, c-myc, N-ras, ets-1, H-ras, c-fos and c-jun,
      apoptosis markers Bax and Bcl-2, tumour suppressor genes p53 and p16, and cell
      proliferation marker Ki-67 in the sequential stages of hamster oral oncogenesis.
      Here, we describe the findings of the experimental model in regard to the
      involvement of signal transduction pathways in every stage of cancer development.
      Increased apoptosis and cell proliferation were observed in early stages of oral
      oncogenesis. Furthermore, the increased expression of transmembrane receptors
      (EGFR, erbB2, FGFR-2 and FGFR-3) as well as the increased expression of nuclear
      transcriptional factors in early stages of oral cancer indicates that these
      molecules may be used as early prognostic factors for the progression of OSCC.
      Since the expression of both H-ras and N-ras do not seem to affect signal
      transduction during oral oncogenesis, it can be assumed that a different
      signalling pathway, such as the PI3K and/or PLCgamma pathway, may be implicated
      in the pathogenesis of OSCC.

PMID- 18061532
TI  - Spectroscopic investigations and crystal structure from synchrotron powder data
      of the inclusion complex of beta-cyclodextrin with atenolol.
AB  - Inclusion complexes of atenolol with beta-cyclodextrin (beta-CD) in aqueous
      solution have been investigated with 1H NMR and UV-vis spectroscopy. The
      stoichiometry of this inclusion complex was established to be equimolar (1:1) and
      its stability constant was determined by UV-vis spectroscopy. The crystal
      structure of the beta-CD-atenolol (1:1) inclusion compound has been solved from
      synchrotron powder diffraction data using direct-space search techniques. The
      crystal structure model and 1H NMR data are in good agreement and, with support
      of Hyperchem MM+ molecular dynamics results, suggest which protons are likely to
      be involved in the inclusion process that leads to the supramolecular
      architecture of this guest-host complex.

PMID- 18061533
TI  - Fluorimetric study of interaction of merbromin with trypsin.
AB  - Interaction of merbromin with trypsin is of bovine origin has been studied by
      monitoring the absorption steady-state and time-resolved fluorescence spectral
      properties of the dye. Studies have been done in media of varying pH at different
      trypsin concentrations. It has been observed that trypsin brings about a
      quenching of fluorescence of the dye. The quenching is static in nature and the
      equilibrium constant of dye-trypsin interaction in the ground-state has been
      determined from quenching studies. Steady-state anisotropy of the dye increases
      in presence of trypsin in the medium. Values of micro-viscosity in the vicinity
      of the fluorophore in media containing trypsin have been determined from
      measurements of fluorescence anisotropy. Time-resolved fluorescence studies
      indicate the existence of two decaying states for the dye. The fractional
      contribution to the time-resolved decay changes with pH. The average lifetime,
      however, does not depend on the concentration of trypsin.

PMID- 18061534
TI  - Synthesis, characterization and DNA interaction studies of complexes of
      lanthanide nitrates with tris(2-[(3,4-dihydroxybenzylidene)imino]ethyl)amine.
AB  - A new tripodal, hydroxyl-rich ligand, tris(2-[(3,4
      dihydroxybenzylidene)imino]ethyl)amine (L), and its complexes with lanthanide
      nitrates were synthesized. These complexes which are stable in air with the
      general formula of [LnL(NO3)2]NO3.H2O (Ln=La, Sm, Eu, Gd, Y) were characterized
      by molar conductivity, elemental analysis, IR spectra and thermal analysis. The
      NO3(-) groups coordinated to lanthanide mono-dentately, and the coordination
      number in these complexes may be 8. The interaction of complexes with DNA were
      investigated by ultraviolet and fluorescent spectra, which showed that the
      binding mode of complexes with DNA was intercalation, and the binding affinity
      with DNA were La(III) complex>Sm(III) complex>Eu(III) complex>Gd(III)
      complex>Y(III) complex. Based on these results, it can be shown that the
      La(III)complex is promising candidate for therapeutic reagents and DNA probes.

PMID- 18061535
TI  - Spectral properties of intramolecular charge transfer fluorescence probe 1-keto-2
      (p-dimethylaminobenzal)-tetrahydronaphthalene.
AB  - The photophysical properties of a new compound 1-keto-2-(p-dimethylaminobenzal)
      tetrahydronaphthalene in various solvents at room temperature were characterized
      by the absorption and steady-state fluorescence technique. The bathochromic shift
      on the emission spectra, the broad halfwidth of the fluorescence band and the
      increase in the excited state dipole moment occurred. These results gave the
      evidence about the intramolecular charge transfer (ICT) character in the emitting
      singlet state of the compound.

PMID- 18061536
TI  - A computer-based aid for communication between patients with limited English and
      their clinicians, using symbols and digitised speech.
AB  - BACKGROUND: Problems of communication are an important barrier on the pathway to
      healthcare for patients with limited or no ability in the majority language of
      the country in which they live. Solutions involving interpreters who have to be
      booked in advance, or using unqualified friends or family members to translate,
      are highly unsatisfactory. AIM: This paper describes a computer-based approach to
      alleviating the situation. DESIGN/METHOD: A computer-based communication aid was
      developed and tested. The communication aid is designed to permit an English
      speaking healthcare practitioner to select a series of questions which are then
      presented along with a range of possible answers for the patient to choose from.
      The questions and answers are presented in the patient's own language in both
      text and digitised speech accompanied by symbols as well as English text. As a
      test-case we focused on Somali patients with asthma. RESULTS: 26 simulated
      consultations with Somali asthma sufferers and healthcare practitioners (three
      GPs and six nurses) with experience of asthma treatment with this patient group
      were held with the system implemented either on a laptop with mouse pad, or a
      tablet with stylus. All the consultations were successfully completed with a high
      satisfaction rate on the part of both practitioners and patients. CONCLUSION:
      Feedback questionnaires suggest some areas for improvement. The proposed system
      is a practical way of addressing the problem of communication with patients with
      limited English in the context of clinician-led question-answer dialogues.

PMID- 18061537
TI  - A fingerprint left by cytomegalovirus infection in the human T cell compartment.
AB  - Latent infection with human cytomegalovirus (HCMV) is accompanied by a strong
      increase in the number of resting, effector-type CD4+ and CD8+ T cells with
      constitutive cytolytic activity in the circulation. Longitudinal studies in
      kidney transplant recipients revealed that effector cells emerge early after the
      initial viral burst and acquire their stable phenotype in the months following
      primary infection. Although it is yet unsettled whether these cells are all
      specific for CMV encoded or induced antigens, it has become clear that T cell
      responses to CMV are among the broadest and strongest analyzed so far. We will
      here summarize the qualities of the effector-type cells found in HCMV carriers
      and discuss their possible role in CMV-associated pathologies.

PMID- 18061538
TI  - Vectorette PCR-primed transposon display using the Jordan transposon in Volvox
      carteri: an efficient tool that analyzes more than 300 Jordan-derived PCR
      fragments to retrieve tagged genes.

PMID- 18061539
TI  - Molecular pharmacology and therapeutic potential of neuronal Kv7-modulating
      drugs.
AB  - The Kv7 potassium channel family encompasses five members (from Kv7.1 to Kv7.5)
      having distinct expression pattern and functional role. Although Kv7.1 is
      prevalently expressed in the cardiac muscle, Kv7.2, Kv7.3, Kv7.4, and Kv7.5 are
      expressed in neural tissue. Mutations in Kv7.2 and/or Kv7.3 genes are responsible
      for an autosomal-dominant epilepsy of the newborn defined as benign familial
      neonatal seizures (BFNS), whereas defects in the Kv7.4 gene have been found in
      families affected by a rare form of nonsyndromic autosomal-dominant hearing loss
      (DFNA2). Compounds acting as direct activators of neuronal channels formed by Kv7
      subunits have been approved for clinical use as analgesics or are in advanced
      stages of clinical evaluation as anticonvulsants; in addition to these
      indications, solid preclinical studies reveal their potential usefulness in other
      diseases characterized by neuronal hyperexcitability. In the present work, we
      will summarize the available evidence providing proof-of-principles that neuronal
      Kv7 channels are highly attractive pharmacological targets, review the molecular
      basis of their peculiar pharmacological sensitivity, introduce some newly
      synthesized I(KM) openers showing improved pharmacokinetic or pharmacodynamic
      properties compared to older congeners, and discuss the potential novel
      therapeutic application of neuronal Kv7 channels in diseases additional to
      epilepsy.

PMID- 18061541
TI  - Pathophysiological aspects of memory B-cell development.
AB  - B cells follow two functionally distinct pathways of development: a classical
      germinal center (GC) T-dependent pathway in which diversification and maturation
      generate a slow, but virtually unlimited high-affinity response to cognate
      antigens; and a marginal zone (MZ) T-independent pathway providing a first line
      of 'innate-like' defense against specific pathogens. Cells populating these two
      distinct locations are the normal counterparts of two clinically important
      pathological entities, follicular lymphoma (FL) and MZ lymphoma (MZL). FL and MZ
      represent paradigms of two rising concepts of lymphomagenesis, protracted
      preclinical and antigen-driven lymphoproliferation, respectively. Integrating the
      mechanisms and functions of MZ and GC B cells and the distinctive features of
      their pathological counterparts should provide essential clues to the
      understanding of their malignant development, and should offer new insights into
      the design of effective treatments for B-cell lymphomas.

PMID- 18061540
TI  - VEGF as a potential target for therapeutic intervention in depression.
AB  - Antidepressants are among the most widely prescribed drugs, however the mechanism
      underlying their therapeutic efficacy is not known. Neurotrophic factors
      represent a promising class of targets for antidepressant treatments. We recently
      characterized a role for vascular endothelial growth factor (VEGF) in cellular
      and behavioral antidepressant responses. VEGF is a potent mitogen and survival
      factor for endothelial cells (ECs) and neurons, and modulator of synaptic
      transmission. Because VEGF has been implicated in a variety of diseases,
      understanding the molecular and cellular specificity of antidepressant-induced
      VEGF will be crucial to determine its potential as a therapeutic target in
      depression.

PMID- 18061544
TI  - Mutation of Tyr375 to Lys375 allows medium-chain acyl-CoA dehydrogenase to
      acquire acyl-CoA oxidase activity.
AB  - Medium-chain acyl-CoA dehydrogenase (MCAD) and acyl-CoA oxidase (ACO) are key
      enzymes catalyzing the rate-determining step for the beta-oxidation of fatty
      acids. Tyr375 of MCAD is conserved in all acyl-CoA dehydrogenases and is an
      important residue for substrate binding. Four Tyr375 variant enzymes of rat liver
      MCAD were obtained through site-directed mutagenesis. Y375K was found to have
      intrinsic acyl-CoA oxidase activity, which was confirmed using HPLC analysis,
      while the wild-type and other Tyr375 variant enzymes did not show detectable
      oxidase activity. The kinetic parameters for the oxidase activity of Y375K
      variant enzyme were determined to be k(cat) of 320+/-80 h(-1) and K(M) of 30+/-15
      microM using hexanoyl-CoA as the substrate. The oxidase activity of Y375K
      increased more than 200 times compared with that reported for the MCAD wild-type
      enzyme from mammalian sources. Molecular modeling study shows that the solvent
      accessible area for Y375K variant enzyme is wider than that of the wild-type
      enzyme, which indicates that Tyr375 may function as a switch against solvent
      accession. The mutation of this residue to Lys375 allows molecular oxygen to
      enter into the catalytic site serving as the electron acceptor for the reduced
      FAD cofactor.

PMID- 18061543
TI  - Blockade of NMDA receptors prevents analgesic tolerance to repeated
      transcutaneous electrical nerve stimulation (TENS) in rats.
AB  - Repeated daily application of transcutaneous electrical nerve stimulation (TENS)
      results in tolerance, at spinal opioid receptors, to the antihyperalgesia
      produced by TENS. Since N-methyl-D-aspartate (NMDA) receptor antagonists prevent
      analgesic tolerance to opioid agonists, we hypothesized that blockade of NMDA
      receptors will prevent tolerance to TENS. In rats with knee joint inflammation,
      TENS was applied for 20 minutes daily at high-frequency (100 Hz), low-frequency
      (4 Hz), or sham TENS. Rats were treated with the NMDA antagonist MK-801 (0.01
      mg/kg to 0.1 mg/kg) or vehicle daily before TENS. Paw withdrawal thresholds were
      tested before and after inflammation and before and after TENS treatment for 4
      days. On day 1, TENS reversed the decreased mechanical withdrawal threshold
      induced by joint inflammation. On day 4, TENS had no effect on the decreased
      withdrawal threshold in the group treated with vehicle, demonstrating development
      of tolerance. However, in the group treated with 0.1 mg/kg MK-801, TENS
      significantly reversed the mechanical withdrawal thresholds on day 4,
      demonstrating that tolerance did not develop. Vehicle-treated animals developed
      cross-tolerance at spinal opioid receptors. Treatment with MK-801 reversed this
      cross-tolerance at spinal opioid receptors. In summary, blockade of NMDA
      receptors prevents analgesic tolerance to daily TENS by preventing tolerance at
      spinal opioid receptors. PERSPECTIVE: Observed tolerance to the clinical
      treatment of TENS could be prevented by administration of pharmaceutical agents
      with NMDA receptors activity such as ketamine or dextromethorphan.

PMID- 18061545
TI  - Replantation of an avulsed ear, using a single arterial anastamosis.
AB  - Avulsion of the ear is relatively uncommon and replantation a technical
      challenge. A case in which an avulsed ear was successfully replanted using a
      single arterial anastamosis is described. The surgical difficulties encountered,
      the pharmaceutical approach to postoperative care and the problems which resulted
      from the lack of venous drainage are discussed.

PMID- 18061546
TI  - Use of the earlobe in auricular reconstruction post tumour extirpation.
AB  - The exact location and topography of defects resulting from surgical excision of
      cutaneous malignancies of the auricle demand a customized approach based on an
      awareness of locally redundant tissue. With advancing age, the earlobe becomes
      ideal for this reconstructive role and we describe an earlobe flap created along
      the longitudinal axis of lobular tissue. This reliable, simple, one-step
      procedure provides adequate tissue cover for defects of the antitragus and
      adjoining concha. Flap vascularity is satisfactory and although the overall size
      of the ear is reduced, this is accepted for a rejuvenated shape and minimal
      morbidity.

PMID- 18061547
TI  - Fasciocutaneous free flaps in pharyngolaryngo-oesophageal reconstruction: a
      critical review of the literature.
AB  - Fasciocutaneous (FC) free flaps are gaining widespread popularity for the
      reconstruction of head and neck defects. The radial forearm free flap and the
      anterolateral thigh flap are now widely used for pharyngolaryngo-oesophageal
      (PLO) reconstruction. In many units these flaps are used in preference to enteric
      free flap reconstructions. This review examined the literature regarding the
      morbidity, mortality and functional outcomes of FC free flap reconstruction of
      PLO defects, particularly with respect to the recent modifications reported in
      the literature. A Medline search was performed for reports published between 1994
      and 2005 and a total of 20 papers were reviewed. Cumulative fistula and stricture
      rates were 13% and 16.1%, respectively, and many surgeons have incorporated
      modifications in the technique to further reduce these rates. These results
      compared favourably to recent reports of enteric reconstructions. Functional
      outcome with the FC free flaps were superior to those reported with jejunal
      flaps, especially with regard to speech following tracheo-oesophageal puncture.
      Following a fasciocutaneous reconstruction, hospital admission time and ICU stay
      were shorter and there were fewer perioperative deaths. Based on this
      comprehensive review of the literature with respect to morbidity, mortality and
      functional outcomes, FC free flap reconstruction of the PLO defect can be
      considered an excellent first line treatment of these difficult defects.

PMID- 18061549
TI  - [Legal and regulatory aspects of living-donor transplantation].
AB  - In France, living-donor organ procurement is regulated in compliance with
      bioethics law n(o) 2004-800 promulgated on 6 August 2004 and the administrative
      decree n(o) 2005-443 of 10 May 2005 which describes the legal framework of
      regional controls and expert committees. These texts make significant changes
      which include: creation of a Biomedicine Agency, a broader definition of
      acceptable donors, expression of consent before the district court, extension of
      expert committee competences, institution of a donor follow-up registry,
      reimbursement of all donation-related expenses. The hospital direction circular
      of 1 March 2005 establishes the funding regulations applied by transplantation
      centers for living-donor transplantation.

PMID- 18061548
TI  - Percutaneous extraction of a knotted pulmonary artery catheter and an entrapped
      tined pacing lead in two dogs.
AB  - Catheters and pacing leads may become entrapped within the heart necessitating
      the use of creative measures for extraction while preventing damage to cardiac
      structures. This report describes the percutaneous extraction of a knotted
      pulmonary artery catheter and an entrapped tined pacing lead in two dogs. In both
      cases, a long transseptal sheath was advanced over the catheter or pacing lead
      and used to facilitate removal of the entrapped devices without causing damage to
      the heart.

PMID- 18061550
TI  - [Psychological aspects of living-donor renal transplantation].
AB  - Psychological support before kidney donation is advocated by all authors, but not
      systematically proposed by all transplantation centers. An analysis of the
      literature shows that there are many positive aspects to organ donation including
      improved self-esteem and quality of life. But many secondary psychological
      effects can also be observed: fear of giving, fear of receiving, laborious
      evaluation period, problems in the event of complications for the donor or graft
      failure, anxiety of the spouses of donators and recipients. Despite these
      problems, donators are highly motivated and very few experience regret after the
      donation, creating a strong(er) donor-recipient relationship after the graft.

PMID- 18061551
TI  - [Global aspects of living donation transplantation].

PMID- 18061552
TI  - [The role of the nephrologist in delivering the information about transplantation
      from a living-donor].
AB  - Eight percent only of the renal transplantations performed each year in France
      are from a living-donor, to be compared with 30-50% in Northern Europe and the
      USA. From the experience of these countries, we understand that to be successful,
      the information has to be delivered early in the course of kidney failure. It
      means that informing the patient about living-donation should be the mission, not
      of the transplant team, but of the patient nephrologist. There are many other
      reasons to give him this initiating role: he has a general vision of the
      treatment of end stage renal disease for this patient as well as a better
      knowledge of his psychological, socioprofessionnal and familial situation and he
      can more easily meet patient's relatives to discuss kidney donation.

PMID- 18061553
TI  - [Informing the living donor].
AB  - Withholding information about the possibility of making a living organ donation
      is not a neutral act: not to inform means to decide on behalf of the potential
      donor and the recipient, and to deny them, without any right and against their
      rights, their free will. It is also to declare implicitly two opinions: first,
      the donor and the recipient are unable to make the right decision; second, the
      ethic and moral convictions of the physician count for more than those of the
      donor and recipient. On the other hand, providing this information is not a
      neutral act either: to the extent that the presentation comes across as
      persuasive or dissuasive, the decision of the recipient and the donor will
      presumably be affected accordingly. Nevertheless, having access to information is
      a minimal condition for the donor and recipient to exercise their free will. For
      this reason, we should try to imagine a system in which patients receive all
      pertinent information about the possibility of a living organ donation, in a
      manner that is not coloured by partisan positions.

PMID- 18061554
TI  - Lost your orientation? Find your way with PtdIns(3,4,5)P3!
AB  - Faithful chromosome segregation requires correct positioning of the spindle
      during mitosis. In this issue of Developmental Cell, Toyoshima et al. describe a
      new mechanism for spindle orientation involving phosphatidylinositol-3,4,5
      triphosphate [PtdIns(3,4,5)P3]. They found that in metaphase cells, dynactin was
      associated with the cortex through the actin cytoskeleton, and accumulated in the
      midsections in a PtdIns(3,4,5)P3-dependent manner. Thus, PtdIns(3,4,5)P3
      regulates spindle orientation through dynein-dynactin motor complexes.

PMID- 18061555
TI  - Opposing effects of Wnt and MAPK on BMP/Smad signal duration.
AB  - Signaling downstream of BMP receptors relies on activated nuclear Smad proteins.
      Recent studies, one of which is published in the November 30 issue of Cell, shed
      light on a mechanism that balances inputs from both activated MAPK and Wnt
      pathways to regulate the proteasomal degradation of Smad1 and thus modulate the
      extent of BMP signaling.

PMID- 18061556
TI  - Losing their minds: Mena/VASP/EVL triple knockout mice.
AB  - A recent Neuron paper by Kwiatkowski et al. that analyzes the phenotypes of mouse
      embryos lacking all members of the Ena/VASP family reveals new roles for these
      molecules in cortical development.

PMID- 18061557
TI  - New phosphatidylserine receptors: clearance of apoptotic cells and more.
AB  - Phagocytes recognize apoptotic cells using cell surface receptors, and
      subsequently engulf these cells. In a recent issue of Nature, two papers reported
      the identification of novel phagocytic receptors that directly interact with
      apoptotic cell surface phosphatidylserine (PS). The studies provide new insights
      into the apoptotic cell clearance process and implicate PS receptors in
      additional signaling events.

PMID- 18061558
TI  - A transcriptome landscape of mouse embryogenesis.
AB  - Coordinated regulation of genetic activity underpins formation of the body plan
      and morphogenesis of embryonic structures. In this issue of Developmental Cell,
      Mitiku and Baker describe a chronological series of transcriptomes of
      postimplantation mouse embryos at gastrulation and early organogenesis, providing
      a valuable resource for studying the dynamics of both genome-wide and gene
      specific transcriptional activities that accompany mouse embryogenesis.

PMID- 18061559
TI  - Hox en provence.
AB  - In the nearly 25 years since the cloning of the first Hox genes, the broad
      brushstrokes of their functions in axial patterning have become familiar motifs
      in developmental biology. The October 2007 Fondation des Treilles workshop on
      "Hox Genes in Development and Evolution" in Les Treilles, France, highlighted
      some of the finer details regarding the function of these genes in shaping animal
      morphology.

PMID- 18061560
TI  - A shared vision.
AB  - One of today's most powerful technologies in biomedical research--the creation of
      mutant mice by gene targeting in embryonic stem (ES) cells--was finally
      celebrated in this year's Nobel Prize in Medicine. The history of how ES cells
      were first discovered and genetically manipulated highlights the importance of
      collaboration among scientists from different backgrounds with a shared vision.

PMID- 18061561
TI  - Drosophila ASPP regulates C-terminal Src kinase activity.
AB  - Src-family kinases (SFKs) control a variety of biological processes, from cell
      proliferation and differentiation to cytoskeletal rearrangements. Abnormal
      activation of SFKs has been implicated in a wide variety of cancers and is
      associated with metastatic behavior (Yeatman, 2004). SFKs are maintained in an
      inactive state by inhibitory phosphorylation of their C-terminal region by C
      terminal Src kinase (Csk). We have identified Drosophila Ankyrin-repeat, SH3
      domain, and Proline-rich-region containing Protein (dASPP) as a regulator of
      Drosophila Csk (dCsk) activity. dASPP is the homolog of the mammalian ASPP
      proteins, which are known to bind to and stimulate the proapoptotic function of
      p53. We show that dASPP is a positive regulator of dCsk. First, dASPP loss-of
      function strongly enhances the specific phenotypes of dCsk mutants in wing
      epithelial cells. Second, dASPP interacts physically with dCsk to potentiate the
      inhibitory phosphorylation of Drosophila Src (dSrc). Our results suggest a role
      for dASPP in maintaining epithelial integrity through dCsk regulation.

PMID- 18061562
TI  - Neuralized contains a phosphoinositide-binding motif required downstream of
      ubiquitination for delta endocytosis and notch signaling.
AB  - The Notch signaling pathway, which plays a critical role in cell-fate decisions
      throughout development, is regulated by endocytosis of both the ligand and
      receptor. Endocytosis of the Drosophila ligands, Delta and Serrate, is required
      in the signaling cell for signal initiation and requires one of two ubiquitin
      ligases, Neuralized or Mind bomb. Through in vitro binding assays we have
      identified an interaction between Neuralized and phosphoinositides, modified
      membrane lipids that mediate membrane trafficking and signaling. We show that
      interactions between phosphoinositides and Neuralized contribute to the membrane
      localization of Neuralized in the absence of Delta, and that the phosphoinositide
      binding motif is required for Neuralized to endocytose Delta downstream of Delta
      ubiquitination. Lastly, we provide evidence that this interaction may also be
      important for vertebrate Neuralized function. These results demonstrate that,
      through interactions with Neuralized, phosphoinositides may regulate Delta
      endocytosis and, by extension, Notch signal transduction.

PMID- 18061563
TI  - PtdIns(3,4,5)P3 regulates spindle orientation in adherent cells.
AB  - Cultured adherent cells divide on the substratum, leading to formation of the
      cell monolayer. However, how the orientation of this anchorage-dependent cell
      division is regulated remains unknown. We have previously shown that integrin
      dependent adhesion orients the spindle parallel to the substratum, which ensures
      this anchorage-dependent cell division. Here, we show that phosphatidylinositol
      3,4,5-triphosphate (PtdIns(3,4,5)P3) is essential for this spindle orientation
      control. In metaphase, PtdIns(3,4,5)P3 is accumulated in the midcortex in an
      integrin-dependent manner. Inhibition of phosphatidylinositol-3-OH kinase
      (PI(3)K) reduces the accumulation of PtdIns(3,4,5)P3 and induces spindle
      misorientation. Introduction of PtdIns(3,4,5)P3 to these cells restores the
      midcortical accumulation of PtdIns(3,4,5)P3 and proper spindle orientation.
      PI(3)K inhibition causes dynein-dependent spindle rotations along the z-axis,
      resulting in spindle misorientation. Moreover, dynactin, a dynein-binding
      partner, is accumulated in the midcortex in a PtdIns(3,4,5)P3-dependent manner.
      We propose that PtdIns(3,4,5)P3 directs dynein/dynactin-dependent pulling forces
      on spindles to the midcortex, and thereby orients the spindle parallel to the
      substratum.

PMID- 18061564
TI  - Stabilization of overlapping microtubules by fission yeast CLASP.
AB  - Many microtubule (MT) structures contain dynamic MTs that are bundled and
      stabilized in overlapping arrays. CLASPs are conserved MT-binding proteins
      implicated in the regulation of MT plus ends. Here, we show that the
      Schizosaccharomyces pombe CLASP, cls1p/peg1p, mediates the stabilization of
      overlapping MTs within the mitotic spindle and interphase bundles. cls1p
      localizes to these regions but not to interphase MT plus ends. Inactivation of
      cls1p leads to the rapid depolymerization of spindle midzone MTs. cls1p also
      stabilizes a subset of MTs within interphase bundles. cls1p prevents disassembly
      of the entire microtubule, while still allowing for plus-end growth. It has no
      measurable effects on MT nucleation, polymerization, catastrophe, or bundling. A
      direct interaction with ase1p (PRC1/MAP65) targets cls1p to regions of
      antiparallel MT overlap. These findings show how a MT-stabilizing factor attached
      to specific sites on MTs can help to generate MT structures that have both
      dynamic and stable components.

PMID- 18061565
TI  - SALS, a WH2-domain-containing protein, promotes sarcomeric actin filament
      elongation from pointed ends during Drosophila muscle growth.
AB  - Organization of actin filaments into a well-organized sarcomere structure is
      critical for muscle development and function. However, it is not completely
      understood how sarcomeric actin/thin filaments attain their stereotyped lengths.
      In an RNAi screen in Drosophila primary muscle cells, we identified a gene,
      sarcomere length short (sals), which encodes an actin-binding, WH2 domain
      containing protein, required for proper sarcomere size. When sals is knocked down
      by RNAi, primary muscles display thin myofibrils with shortened sarcomeres and
      increased sarcomere number. Both loss- and gain-of-function analyses indicate
      that SALS may influence sarcomere lengths by promoting thin-filament lengthening
      from pointed ends. Furthermore, the complex localization of SALS and other
      sarcomeric proteins in myofibrils reveals that the full length of thin filaments
      is achieved in a two-step process, and that SALS is required for the second
      elongation phase, most likely because it antagonizes the pointed-end capping
      protein Tropomodulin.

PMID- 18061566
TI  - Control of plant organ size by KLUH/CYP78A5-dependent intercellular signaling.
AB  - Plant organs grow to characteristic sizes that are genetically controlled. In
      animals, signaling by mobile growth factors is thought to be an effective
      mechanism for measuring primordium size, yet how plants gauge organ size is
      unclear. Here, we identify the Arabidopsis cytochrome P450 KLUH (KLU)/CYP78A5 as
      a stimulator of plant organ growth. While klu loss-of-function mutants form
      smaller organs because of a premature arrest of cell proliferation, KLU
      overexpression leads to larger organs with more cells. KLU promotes organ growth
      in a non-cell-autonomous manner, yet it does not appear to modulate the levels of
      known phytohormones. We therefore propose that KLU is involved in generating a
      mobile growth signal distinct from the classical phytohormones. The expression
      dynamics of KLU suggest a model of how the arrest of cell proliferation is
      coupled to the attainment of a certain primordium size, implying a common
      principle of size measurement in plants and animals.

PMID- 18061567
TI  - Prothoracicotropic hormone regulates developmental timing and body size in
      Drosophila.
AB  - In insects, control of body size is intimately linked to nutritional quality as
      well as environmental and genetic cues that regulate the timing of developmental
      transitions. Prothoracicotropic hormone (PTTH) has been proposed to play an
      essential role in regulating the production and/or release of ecdysone, a steroid
      hormone that stimulates molting and metamorphosis. In this report, we examine the
      consequences on Drosophila development of ablating the PTTH-producing neurons.
      Surprisingly, PTTH production is not essential for molting or metamorphosis.
      Instead, loss of PTTH results in delayed larval development and eclosion of
      larger flies with more cells. Prolonged feeding, without changing the rate of
      growth, causes the overgrowth and is a consequence of low ecdysteroid titers.
      These results indicate that final body size in insects is determined by a balance
      between growth-rate regulators such as insulin and developmental timing cues such
      as PTTH that set the duration of the feeding interval.

PMID- 18061568
TI  - Snail1 is a transcriptional effector of FGFR3 signaling during chondrogenesis and
      achondroplasias.
AB  - Achondroplasias are the most common genetic forms of dwarfism in humans. They are
      associated with activating mutations in FGFR3, which signal through the Stat and
      MAPK pathways in a ligand-independent manner to impair chondrocyte proliferation
      and differentiation. Snail1 has been implicated in chondrocyte differentiation as
      it represses Collagen II and aggrecan transcription in vitro. Here we demonstrate
      that Snail1 overexpression in the developing bone leads to achondroplasia in
      mice. Snail1 acts downstream of FGFR3 signaling in chondrocytes, regulating both
      Stat and MAPK pathways. Moreover, FGFR3 requires Snail1 during bone development
      and disease as the inhibition of Snail1 abolishes its signaling even through
      achondroplastic- and thanatophoric-activating FGFR3 forms. Significantly, Snail1
      is aberrantly upregulated in thanatophoric versus normal cartilages from
      stillborns. Thus, Snail activity may likely be considered a target for
      achondroplasia therapies.

PMID- 18061569
TI  - Live imaging and genetic analysis of mouse notochord formation reveals regional
      morphogenetic mechanisms.
AB  - The node and notochord have been extensively studied as signaling centers in the
      vertebrate embryo. The morphogenesis of these tissues, particularly in mouse, is
      not well understood. Using time-lapse live imaging and cell lineage tracking, we
      show the notochord has distinct morphogenetic origins along the anterior
      posterior axis. The anterior head process notochord arises independently of the
      node by condensation of dispersed cells. The trunk notochord is derived from the
      node and forms by convergent extension. The tail notochord forms by node-derived
      progenitors that actively migrate toward the posterior. We also reveal distinct
      genetic regulation within these different regions. We show that Foxa2 compensates
      for and genetically interacts with Noto in the trunk notochord, and that Noto has
      an evolutionarily conserved role in regulating axial versus paraxial cell fate.
      Therefore, we propose three distinct regions within the mouse notochord, each
      with unique morphogenetic origins.

PMID- 18061570
TI  - Genomic analysis of gastrulation and organogenesis in the mouse.
AB  - We developed a comprehensive dataset that samples the mouse transcriptome every 6
      hr, from gastrulation through organogenesis. We observe an abrupt increase in
      overall transcript diversity at the onset of organogenesis (e8.0); the genes that
      comprise these changes are preferentially clustered along chromosome 7 and
      contain a significant enrichment of Gli binding sites. Furthermore, we identify
      seven dominant patterns of gene expression during gastrulation and organogenesis.
      Genes clustered according to these seven patterns constitute distinct functional
      classes, including a cluster enriched for gastrulation and pluripotency genes,
      two clusters differentially regulating localization and ion metabolism, and three
      clusters involved in discrete aspects of organogenesis. The last cluster is
      defined by a dramatic transient decrease in the expression of genes that regulate
      RNA processing and the cell cycle. Drosophila homologs of these genes are also
      coordinately downregulated following gastrulation, suggesting that the combined
      function of these genes has been conserved during metazoan evolution.

PMID- 18061571
TI  - Transcriptional response to muscarinic acetylcholine receptor stimulation:
      regulation of Egr-1 biosynthesis by ERK, Elk-1, MKP-1, and calcineurin in
      carbachol-stimulated human neuroblastoma cells.
AB  - Carbachol-mediated activation of type M(3) muscarinic acetylcholine receptors
      induces the biosynthesis of the transcription factor Egr-1 in human SH-SY5Y
      neuroblastoma cells involving an activation of extracellular signal-regulated
      protein kinase. Carbachol triggered the phosphorylation of the ternary complex
      factor Elk-1, a key transcriptional regulator of serum response element-driven
      gene transcription, and strikingly enhanced the transcriptional activation
      potential of Elk-1. Chromatin immunoprecipitation experiments revealed that Elk-1
      binds in vivo to the 5'-upstream region of the Egr-1 gene in carbachol-stimulated
      neuroblastoma cells. Together, these data indicate that Elk-1 connects the
      intracellular signaling cascade elicited by activation of M(3) muscarinic
      acetylcholine receptors with the transcription of the Egr-1 gene. Lentiviral
      mediated expression of either MAP kinase phosphatase-1 (MKP-1) or a
      constitutively active mutant of calcineurin A inhibited Egr-1 biosynthesis
      following carbachol stimulation, indicating that these phosphatases function as
      shut-off devices of muscarinic acetylcholine receptor signaling. Additionally,
      carbachol stimulation increased transcription of a chromatin-embedded collagenase
      promoter/reporter gene, showing that AP-1 activity is enhanced in carbachol
      stimulated neuroblastoma. Expression experiments revealed that both MKP-1 and a
      constitutively active mutant of calcineurin A impaired carbachol-induced
      upregulation of AP-1 activity. The fact that carbachol stimulation of
      neuroblastoma cells activates the transcription factors Egr-1 and AP-1 suggests
      that changes in the gene expression pattern are an integral part of muscarinic
      acetylcholine receptor signaling.

PMID- 18061573
TI  - Immunocytochemical analysis for intracellular dynamics of C1GalT associated with
      molecular chaperone, Cosmc.
AB  - The core 1 structure Galbeta1-3GalNAcalpha1-Ser/Thr (T antigen), the major
      constituent of O-glycan core structure, is synthesized by cooperation of core 1
      synthase (C1GalT) and its specific molecular chaperone, Cosmc. The chaperone
      function of Cosmc has been well investigated biochemically. In this study, we
      established monoclonal antibodies specifically recognizing either C1GalT or
      Cosmc, respectively, and investigated the sub-cellular localization of each
      protein to elucidate how they cooperate to synthesize the core 1 structure. A
      sequential immunocytochemical analysis of the human colon cancer cell line, LSB,
      demonstrated different localization of two proteins. C1GalT was localized in
      Golgi apparatus, while Cosmc was localized in endoplasmic reticulum. In contrast,
      the LSC cells, which do not have core 1 synthase activity due to a missense
      mutation in the Cosmc gene, did not express the C1GalT protein. Although the
      treatment with a proteasome inhibitor, lactacystin, of LSC cells resulted in the
      increased expression of C1GalT protein, the distribution of C1GalT was not in
      Golgi apparatus as seen in LSB cells. On the contrary, overexpression of Cosmc
      but not C1GalT lead to precise localization of C1GalT protein, which distributed
      in Golgi apparatus and recovered the core 1 synthase activity in LSC cells. These
      results suggest that the intracellular dynamics of C1GalT is controlled by its
      specific molecular chaperon, Cosmc, in association with core 1 synthase activity.

PMID- 18061572
TI  - Length-dependent activation and auto-oscillation in skeletal myofibrils at
      partial activation by Ca2+.
AB  - The length-dependent activation of skeletal myofibrils was examined at the single
      sarcomere level with phase-contrast microscopy at sarcomere length (SL) >2.2
      microm. At the maximal activation by Ca(2+) (pCa 4.5) the active force linearly
      decreased with increasing SL, while at partial activation by Ca(2+) (pCa 6.1-6.5)
      the larger active force was generated at longer SL. Throughout these experiments,
      the distribution of SL was kept homogeneous upon activation. In addition, we
      found that the spontaneous oscillation of force and SL frequently occurs in the
      SL range 2.2-2.6 microm at pCa 6.1-6.2. Either changes in [Ca(2+)] or osmotic
      compression of the myofilament lattice induced by the addition of dextran T-500,
      affected both the length dependence of activation and the occurrence of auto
      oscillation. These results suggest that the force-generating properties of
      sarcomeres in striated muscle are determined not only by [Ca(2+)], but also by
      the lattice spacing as a function of SL.

PMID- 18061574
TI  - Synthesis of aromatic triols and triacids from oleic and erucic acid: separation
      and characterization of the asymmetric and symmetric isomers.
AB  - Hexasubstituted benzene derivatives, aromatic triols 4, 9 and triacids 5, 10 have
      been synthesized from oleic and erucic acid derivatives followed by a
      cyclotrimerization step catalyzed by palladium-on-carbon (Pd/C) and
      chlorotrimethylsilane (TMSCl). The asymmetric isomer, which is the main product,
      was isolated from its symmetric isomer by flash chromatography. All the products
      were fully characterized by IR, (1)H NMR, (13)C NMR and mass spectrometry. The
      products are suitable monomers for the production of polyurethanes, polyesters
      and polyamides.

PMID- 18061575
TI  - A multicenter evaluation of the PCA3 molecular urine test: pre-analytical
      effects, analytical performance, and diagnostic accuracy.
AB  - BACKGROUND: Measurement of prostate cancer gene 3 (PCA3) mRNA normalized to
      prostate-specific antigen (PSA) mRNA in urine has been proposed as a marker for
      prostate cancer. METHODS: We investigated pre-analytical effects, analytical
      performance, and diagnostic accuracy of a quantitative assay for PCA3. RESULTS:
      Urine specimens collected without prostate manipulation demonstrated low
      informative rates. However, specimens collected following digital rectal
      examinations of 3 or 8 strokes per prostate lobe demonstrated informative rates
      >94%. Across all urine specimen types, median PCA3 results did not show
      statistically significant differences (P>0.8). Measurements of controls of known
      mRNA content demonstrated percent recoveries of 100+/-15% for both PCA3 and PSA
      mRNAs. PCA3 mRNA total, intra-assay, inter-assay, and inter-site CVs were < or
      =17.1%, < or =14.0%, < or =9.9%, and < or =3.2%, respectively. Corresponding CVs
      for PSA mRNA assay were < or =11.5%, < or =8.6%, < or =7.9%, and < or =8.3%.
      Blinded assay of urines from 72 men with known prostate biopsy outcomes yielded
      areas under the curve from receiver-operating characteristic analysis of 0.7 at
      both research sites. Deming regression of individual PCA3 results between sites
      yielded slope=0.94, intercept=0.48, R=0.9677 (P<0.0001). CONCLUSIONS: The PCA3
      assay is insensitive to pre-analytical factors, performs well analytically and
      correctly classifies a high percent of subjects with known prostate cancer status
      across research sites.

PMID- 18061576
TI  - Comparison of various methods for amniotic fluid DeltaOD450 bilirubin
      measurement.
AB  - BACKGROUND: The purpose of this study was to investigate the degree of DeltaOD450
      method variability and its effect on DeltaOD450 measurements between selected
      clinical laboratories in the U.S. METHOD: Four amniotic fluid specimens were sent
      to 7 clinical laboratories in the U.S. for DeltaOD450 analysis. In addition,
      scanning spectrophotometric data from 152 amniotic fluid samples were used to
      compare DeltaOD450 values calculated using both log and linear OD scales.
      RESULTS: We found that no 2 laboratories used exactly the same method and no
      laboratory used precisely the same method as originally described by Liley.
      Despite the varied methods, the DeltaOD450 measurements were remarkably similar.
      The exception was 1 sample that was subjected to chloroform extraction. The
      DeltaOD450 measurement on this sample was 82% lower than the mean. On average,
      DeltaOD450 results determined from a linear OD scale were 37% lower than those
      determined from a log scale. CONCLUSION: Although there is no standard method for
      performing the DeltaOD450, inter-laboratory variation of DeltaOD450 results is
      remarkably small. As our and other previous studies have reported, these data
      suggest that both chloroform extraction and use of a linear scale have the
      potential to result in lower DeltaOD450 results.

PMID- 18061577
TI  - Effect of uncoupling protein-1 expression on 3T3-L1 adipocyte gene expression.
AB  - The mitochondrial respiratory uncoupling protein 1 (UCP1) partially uncouples
      substrate oxidation and oxidative phosphorylation to promote the dissipation of
      cellular biochemical energy as heat in brown adipose tissue. We have recently
      shown that expression of UCP1 in 3T3-L1 white adipocytes reduces the accumulation
      of triglycerides. Here, we investigated the molecular basis underlying UCP1
      expression in 3T3-L1 adipocytes. Gene expression data showed that forced UCP1
      expression down-regulated several energy metabolism pathways; but ATP levels were
      constant. A metabolic flux analysis model was used to reflect the gene expression
      changes onto metabolic processes and concordance was observed in the down
      regulation of energy consuming pathways. Our data suggest that adipocytes respond
      to long-term mitochondrial uncoupling by minimizing ATP utilization.

PMID- 18061578
TI  - Correlation between cellulose binding and activity of cellulose-binding domain
      mutants of Humicola grisea cellobiohydrolase 1.
AB  - The cellulose-binding domains (CBDs) of fungal cellulases interact with
      crystalline cellulose through their hydrophobic flat surface formed by three
      conserved aromatic amino acid residues. To analyze the functional importance of
      these residues, we constructed CBD mutants of cellobiohydrolase 1 (CBH1) of the
      thermophilic fungus Humicola grisea, and examined their cellulose-binding ability
      and enzymatic activities. High activity on crystalline cellulose correlated with
      high cellulose-binding ability and was dependent on the combination and
      configuration of the three aromatic residues. Tyrosine works best in the middle
      of the flat surface, while tryptophan is the best residue in the two outer
      positions.

PMID- 18061580
TI  - Direct neurite-osteoblastic cell communication, as demonstrated by use of an in
      vitro co-culture system.
AB  - Using an in vitro co-culture approach comprising cultured murine superior
      cervical ganglia and MC3T3-E1 osteoblast-like cells, we found that the addition
      of scorpion venom (SV) elicited neurite activation via intracellular Ca2+
      mobilization and, after a lag period, osteoblastic Ca2+ mobilization. SV did not
      have any direct effect on the osteoblastic cells in the absence of neurites. The
      addition of an alpha1-adrenergic receptor (AR) antagonist, prazosin, dose
      dependently prevented the osteoblastic activation that resulted as a consequence
      of neural activation by SV. These results demonstrate that osteoblastic
      activation occurred as a direct response to neuronal activation, which activation
      was mediated by alpha1-ARs in the osteoblastic cells.

PMID- 18061579
TI  - Neuronal control of energy homeostasis.
AB  - Neuronal control of body energy homeostasis is the key mechanism by which animals
      and humans regulate their long-term energy balance. Various hypothalamic neuronal
      circuits (which include the hypothalamic melanocortin, midbrain dopamine reward
      and caudal brainstem autonomic feeding systems) control energy intake and
      expenditure to maintain body weight within a narrow range for long periods of a
      life span. Numerous peripheral metabolic hormones and nutrients target these
      structures providing feedback signals that modify the default "settings" of
      neuronal activity to accomplish this balance. A number of molecular genetic tools
      for manipulating individual components of brain energy homeostatic machineries,
      in combination with anatomical, electrophysiological, pharmacological and
      behavioral techniques, have been developed, which provide a means for elucidating
      the complex molecular and cellular mechanisms of feeding behavior and metabolism.
      This review will highlight some of these advancements and focus on the neuronal
      circuitries of energy homeostasis.

PMID- 18061581
TI  - Imatinib interferes with survival of multi drug resistant Kaposi's sarcoma cells.
AB  - Multi drug resistance (MDR) is defined as the ability of tumor cells to become
      resistant to unrelated drugs. Tyrosine kinase inhibitor imatinib has been
      demonstrated to be effective in the treatment of certain tumors. In particular,
      imatinib inhibits Bcr-Abl kinase activity, c-kit and the phosphorylation of
      platelet-derived growth factor (PDGF) receptors. In this work, we show that
      imatinib inhibits PDGF phosphorylation not only in wt Kaposi sarcoma (KS) but
      also in multi drug resistant KS cells. This was associated with an increased
      apoptosis in wt cells and an increased autophagy in MDR-KS cells. These data add
      new insights to the possible use of imatinib in the overcoming of MDR in KS
      cells.

PMID- 18061582
TI  - X-ray structure of the PHF core C-terminus: insight into the folding of the
      intrinsically disordered protein tau in Alzheimer's disease.
AB  - The major constituent of Alzheimer's disease paired helical filaments (PHF) core
      is intrinsically disordered protein (IDP) tau. In spite of a considerable effort,
      insoluble character of PHF together with inherent physical properties of IDP tau
      have precluded so far reconstruction of PHF 3D structure by X-ray crystallography
      or NMR spectroscopy. Here we present first crystallographic study of PHF core C
      terminus. Using monoclonal antibody MN423 specific to the tertiary structure of
      the PHF core, the in vivo PHF structure was imprinted into recombinant core PHF
      tau. Crystallization of the complex led to determination of the structure of the
      core PHF tau protein fragment 386TDHGAE391 at 1.65A resolution. Structural
      analysis suggests important role of the core PHF C-terminus for PHF assembly. It
      is reasonable to expect that this approach will help to reveal the structural
      principles underlying the tau protein assembly into PHF and possibly will
      facilitate rationale drug design for inhibition of Alzheimer neurofibrillary
      changes.

PMID- 18061583
TI  - Inhibition of SH2-domain containing inositol phosphatase 2 (SHIP2) in insulin
      producing INS1E cells improves insulin signal transduction and induces
      proliferation.
AB  - Inhibition of the lipid phosphatase SH2-domain containing inositol phosphatase 2
      (SHIP2) in L6-C10 muscle cells, in 3T3-L1 adipocytes and in the liver of db/db
      mice has been shown to ameliorate insulin signal transduction and established
      SHIP2 as a negative regulator of insulin action. Here we show that SHIP2
      inhibition in INS1E insulinoma cells increased Akt, glycogen synthase kinase 3
      and extracellular signal-regulated kinases 1 and 2 phosphorylation. SHIP2
      inhibition did not prevent palmitate-induced apoptosis, but increased cell
      proliferation. Our data raise the interesting possibility that SHIP2 inhibition
      exerts proliferative effects in beta-cells and further support the attractiveness
      of a specific inhibition of SHIP2 for the treatment of type 2 diabetes.

PMID- 18061584
TI  - Characterization of a novel vanadium-binding protein (VBP-129) from blood plasma
      of the vanadium-rich ascidian Ascidia sydneiensis samea.
AB  - The ascidians, the so-called sea squirts, accumulate high levels of vanadium, a
      transition metal. Since Henze first observed this physiologically unusual
      phenomenon about one hundred years ago, it has attracted interdisciplinary
      attention from chemists, physiologists, and biochemists. The maximum
      concentration of vanadium in ascidians can reach 350 mM, and most of the vanadium
      ions are stored in the +3 oxidation state in the vacuoles of vanadium
      accumulating blood cells known as vanadocytes. Many proteins involved in the
      accumulation and reduction of vanadium in the vanadocytes, blood plasma, and
      digestive tract have been identified. However, the process by which vanadium is
      taken in prior to its accumulation in vanadocytes has not been elucidated. In the
      present study, a novel vanadium-binding protein, designated VBP-129, was
      identified from blood plasma of the vanadium-rich ascidian Ascidia sydneiensis
      samea. Although VBP-129 mRNA was transcribed in all A. sydneiensis samea tissues
      examined, the VBP-129 protein was exclusively localized in blood plasma and
      muscle cells of this ascidian. It bound not only to VO(2+) but also to Fe(3+),
      Co(2+), Cu(2+), and Zn(2+); on the other hand, a truncated form of VBP-129,
      designated VBP-88, bound only to Co(2+), Cu(2+) and Zn(2+). In a pull-down assay,
      an interaction between VanabinP and VBP-129 occurred both in the presence and the
      absence of VO(2+). These results suggest that VBP-129 and VanabinP function
      cooperatively as metallochaperones in blood plasma.

PMID- 18061585
TI  - Flavonoids induce HIF-1alpha but impair its nuclear accumulation and activity.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is the regulatory subunit of the
      transcription factor HIF-1, which is highly involved in the pathology of diseases
      associated with tissue hypoxia. In this study we investigated the ability of
      plant flavonoids to induce HIF-1alpha and regulate HIF-1 transcriptional activity
      in HeLa cells. We demonstrate for the first time that the flavonoids baicalein,
      luteolin and fisetin, as well as the previously investigated quercetin, induce
      HIF-1alpha under normal oxygen pressure, whereas kaempferol, taxifolin, and rutin
      are inactive. We further reveal that the capability of flavonoids to bind
      efficiently intracellular iron and their lipophilicity are essential for HIF
      1alpha induction. Despite the ability of flavonoids to stabilize HIF-1alpha, the
      transcriptional activity of HIF-1 induced by flavonoids was significantly lower
      than that observed with the iron chelator and known HIF-1 inducer,
      desferrioxamine (DFO). Furthermore, when cells in which HIF-1 had been induced by
      DFO were also treated with flavonoids, the transcriptional activity of HIF-1 was
      strongly impaired without simultaneous reduction in HIF-1alpha protein levels.
      Localization of HIF-1alpha by immuno- and direct fluorescence microscopy and in
      vitro phosphorylation assays suggest that flavonoids inhibit HIF-1 activity by
      impairing the MAPK-dependent phosphorylation of HIF-1alpha, thereby decreasing
      its nuclear accumulation.

PMID- 18061586
TI  - Bridging small-gap peripheral nerve defects using acellular nerve allograft
      implanted with autologous bone marrow stromal cells in primates.
AB  - This study evaluated the effects of the transplantation of a tissue-engineered
      nerve derived from an acellular allogenic nerve graft, combined with autologous
      bone marrow stromal cells (MSCs), into peripheral nerve defects. In a rhesus
      monkey model, nerve regeneration was evaluated across a 1-cm lesion in the radial
      nerve by using an acellular allogenic nerve injected with autologous MSCs. Simple
      acellular nerve allografts served as control. Eight weeks after surgery,
      immunofluorescence staining, histologic morphometrical analysis and
      electrophysiologic evaluation were performed. Fluorescence microscopy revealed
      that some MSCs were immunopositive to S-100 protein, indicating a Schwann cell
      (SC) phenotype. The group treated with cultured MSCs showed a statistically
      higher number of nerve fibers, with well-shaped remyelinated axons. The motor
      conduction velocities and the peak amplitudes of compound muscle action
      potentials (CMAP) for the group treated with MSCs were higher than those of the
      controls. This outcome indicated that MSCs are able to differentiate into Schwann
      like cells in vivo and to promote nerve regeneration in primates. Furthermore,
      the acellular nerves injected with MSCs provided a favorable environment for the
      growth and myelination of regenerating axons when compared to acellular nerves
      alone.

PMID- 18061587
TI  - A simple and rapid HPLC method for the detection of glyburide in plasma original
      research communication (analytical).
AB  - INTRODUCTION: Although a variety of HPLC methods have been previously described
      for the quantification of glyburide, attempts to implement them clinically have
      been unsuccessful. Some are time consuming, expensive, or not directly applicable
      to human plasma. Others are outdated, as the necessary materials are no longer
      available. OBJECTIVE: To describe a simple, rapid, and sensitive HPLC method for
      the analysis of human plasma and perfusate. DESIGN AND METHOD: Samples were
      extracted by liquid-liquid extraction with chloroform at neutral pH. Glyburide
      was detected at 254 nm, with a total run time of 7 min per sample. RESULTS:
      Standard curves of 50 to 400 ng/mL of glyburide were linear (r(2)=0.998). Inter
      day and intra-day sample coefficient of variations were 8% and 4%, respectively.
      Recoveries ranged from 71 to 75% in human plasma samples for the 20-400 ng/mL
      concentration range. CONCLUSION: Clinically, this method can be applied in the
      therapeutic drug monitoring of glyburide.

PMID- 18061588
TI  - Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and their association
      with clinical outcome, troponin T and C-reactive protein in patients with acute
      coronary syndromes.
AB  - OBJECTIVES: The aim of this study was to compare concentrations of soluble
      intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule
      (VCAM-1) in patients with coronary artery disease and healthy control and to
      evaluate the usefulness of the inflammatory markers as predictors of adverse
      prognosis in patients with acute coronary syndromes (ACS). DESIGN AND METHODS:
      ELISA was used to measure sICAM-1 and sVCAM-1 levels in 75 patients with ACS, 36
      patients with stable angina pectoris (SAP) and 25 healthy subjects. hsCRP was
      measured with immunoturbidimetric assay, cardiac troponin T-with
      electrochemiluminescence immunoassay. RESULTS: All soluble ICAM-1 and VCAM-1
      significantly discriminated between patients with ACS and SAP (p=0.014 and 0.05,
      respectively) and control subjects (p<0.001 and 0.05). During the 6-month follow
      up of the patients with ACS, there were 28 major cardiac events (37.3%). The odds
      ratio associated with the highest value of sVCAM-1 was 4.62 (95% CI 1.8-11.4,
      p=0.0009) without adjustment and remained significantly elevated after adjustment
      for cTnT (RR 3.93, 1.5-10, p=0.04) and hsCRP (RR 2.22, 0.8-5.7, p=0.05). In
      contrast, an elevated level of sICAM-1 was not associated with future coronary
      risk after adjustment for cTnT and hsCRP. CONCLUSIONS: In patients with acute
      coronary syndromes, VCAM-1 serum levels powerfully predict an increased risk for
      subsequent cardiovascular events and extend the prognostic information gained
      from traditional biochemical markers.

PMID- 18061589
TI  - Techniques for clustering gene expression data.
AB  - Many clustering techniques have been proposed for the analysis of gene expression
      data obtained from microarray experiments. However, choice of suitable method(s)
      for a given experimental dataset is not straightforward. Common approaches do not
      translate well and fail to take account of the data profile. This review paper
      surveys state of the art applications which recognise these limitations and
      addresses them. As such, it provides a framework for the evaluation of clustering
      in gene expression analyses. The nature of microarray data is discussed briefly.
      Selected examples are presented for clustering methods considered.

PMID- 18061590
TI  - Indoor and outdoor air carbonyl compounds correlation elucidated by principal
      component analysis.
AB  - In this study indoor and outdoor air carbonyl compounds concentrations data are
      processed by means of principal component analysis (PCA). The analysis pointed to
      the carbonyl compounds sources as well as to their mutual interrelations. A
      global six sources (components) solution, accounting for the joint variability of
      the measured variables, was obtained. The existence of a linear function
      connecting outdoor and indoor components allowed for an exchange model between
      indoor and outdoor carbonyl compounds to be outlined. The different sources of
      carbonyl compounds were tentatively identified. Overall, this work demonstrates
      the presence of a delicate balance between indoor and outdoor carbonyl compounds
      contamination with the two compartments (indoor and outdoor) engaged in a close
      relationship.

PMID- 18061591
TI  - Human neural progenitor cells over-expressing IGF-1 protect dopamine neurons and
      restore function in a rat model of Parkinson's disease.
AB  - Growth factors such as glial cell line-derived neurotrophic factor (GDNF) have
      been shown to prevent neurodegeneration and promote regeneration in many animal
      models of Parkinson's disease (PD). Insulin-like growth factor 1 (IGF-1) is also
      known to have neuroprotective effects in a number of disease models but has not
      been extensively studied in models of PD. We produced human neural progenitor
      cells (hNPC) releasing either GDNF or IGF-1 and transplanted them into a rat
      model of PD. hNPC secreting either GDNF or IGF-1 were shown to significantly
      reduce amphetamine-induced rotational asymmetry and dopamine neuron loss when
      transplanted 7 days after a 6-hydroxydopamine (6-OHDA) lesion. Neither
      untransduced hNPC nor a sham transplant had this effect suggesting GDNF and IGF-1
      release was required. Interestingly, GDNF, but not IGF-1, was able to protect or
      regenerate tyrosine hydroxylase-positive fibers in the striatum. In contrast, IGF
      1, but not GDNF, significantly increased the overall survival of hNPC both in
      vitro and following transplantation. This suggests a dual role of IGF-1 to both
      increase hNPC survival after transplantation and exert trophic effects on
      degenerating dopamine neurons in this rat model of PD.

PMID- 18061592
TI  - Fetal cardiac activity at 4 weeks after in vitro fertilization predicts
      successful completion of the first trimester of pregnancy.
AB  - OBJECTIVE: To determine the predictive value of fetal cardiac activity (FCA),
      measured at 6 weeks' gestation, on first-trimester pregnancy success after IVF.
      DESIGN: Retrospective cohort study. SETTING: University-based reproductive
      endocrinology and infertility practice. PATIENT(S): One hundred thirty-nine
      women, without a history of recurrent miscarriage, who were undergoing fresh IVF
      cycles from August 1, 2004 to February 28, 2005. INTERVENTION(S): Transvaginal
      ultrasound. MAIN OUTCOME MEASURE(S): First-trimester pregnancy success.
      RESULT(S): Ninety-three percent (51/53) of gestational sacs with FCA completed
      the first trimester (positive predictive value of 93%). Eighty-seven percent
      (13/15) of sacs without FCA failed in the first trimester (negative predictive
      value of 87%). In singletons, the positive and negative predictive value of FCA
      on first-trimester success was 100%. All twin pregnancies (n = 11) successfully
      completed the first trimester. CONCLUSION(S): This analysis, which was performed
      strictly in an IVF population with no history of recurrent pregnancy loss,
      demonstrates that positive FCA at 6 weeks' gestation is an excellent predictor of
      first-trimester pregnancy outcome.

PMID- 18061593
TI  - Preimplantation genetic screening to improve in vitro fertilization pregnancy
      rates: a prospective randomized controlled trial.
AB  - This prospective randomized controlled pilot trial was designed to evaluate
      whether prescreening embryos for aneuploidy can improve clinical outcomes in
      infertile patients undergoing IVF, without limiting to poor prognosis patients.
      Although there was no statistically significant improvement in live birth rates
      or implantation rates in this pilot study, there was a trend toward improved
      clinical outcomes, indicating that future multicenter randomized trials are
      needed.

PMID- 18061594
TI  - Infection after ERCP, and antibiotic prophylaxis: a sequential quality
      improvement approach over 11 years.
AB  - BACKGROUND: Infection is a known complication of ERCP procedures, and the role of
      antibiotic prophylaxis is uncertain. OBJECTIVE: To document the incidence of
      infection after ERCP while changing the policy for antibiotic prophylaxis.
      DESIGN: Retrospective analysis of data collected prospectively on infection
      complications, with progressive reduction in the use of prophylactic antibiotics.
      SETTING: Single-center university referral hospital. PATIENTS: A total of 11,484
      ERCP procedures were documented prospectively over a period of 11 years.
      INTERVENTIONS: After baseline assessment, the use of prophylactic antibiotics was
      sequentially reduced and simplified in 3 phases. MAIN OUTCOME MEASUREMENTS:
      Incidence of infection, categorized by severity. RESULTS: The infection rate was
      low overall and decreased significantly with time, from 0.48% to 0.25%, despite a
      marked reduction in the proportion of patients given antibiotics (from 95% to
      25%). Multivariate analysis also showed that the only category of patients at
      increased risk for infection (despite antibiotics) was the subgroup undergoing
      interventions for biliary problems after liver transplantation. LIMITATIONS: A
      lack of routine follow-up may mean that some delayed infectious complications
      were not recorded. The low risk of infection in this series may reflect the high
      technical success rate for relief of biliary obstruction; thus, our current
      minimalist antibiotic policy may not be generalizable to community practice.
      CONCLUSIONS: Infectious complications of ERCP can be kept to a minimum with a
      limited use of prophylactic antibiotics.

PMID- 18061595
TI  - Complications after ERCP in patients with primary sclerosing cholangitis.
AB  - BACKGROUND: There are conflicting data regarding the role of ERCP in patients
      with primary sclerosing cholangitis (PSC) and the risk of procedure-related
      complications. OBJECTIVE: We compared the complication rate after ERCP in a
      consecutive series of patients with PSC compared with control patients with
      biliary strictures who did not have PSC. DESIGN: Retrospective cross-sectional
      study. SETTING: A tertiary referral academic hospital. MAIN OUTCOME MEASUREMENTS:
      Incidence of complications after ERCP. PATIENTS AND RESULTS: A total of 85 ERCPs
      among 30 patients with PSC and 70 ERCPs among 45 control patients were reviewed.
      There was no significant difference in the overall complication rates between
      patients with and without PSC (11/85 [12.9%] vs 6/70 [8.6%], P = .45).
      Complications in PSC were more likely to occur after ERCP done to evaluate an
      acute sign or symptom than in elective cases (7/24 [29.2%] vs 4/61 [6.6%], P =
      .01). Patients with PSC who had complications had more total and acute ERCPs than
      did those without complications. There was no significant difference in the rate
      of complications in diagnostic versus therapeutic ERCPs nor between stent
      placement and dilation-only therapeutic ERCPs in the PSC population. LIMITATIONS:
      Retrospective study design and limited power related to the small sample sizes.
      CONCLUSIONS: Elective ERCP is safe and carries a modest risk in patients with
      PSC; however, ERCP for acute indications greatly increases the probability of
      postprocedure complications. The overall complication rate after therapeutic ERCP
      in patients with PSC is similar to that in patients without PSC.

PMID- 18061596
TI  - Optimal band imaging system can facilitate detection of changes in depressed-type
      early gastric cancer.
AB  - BACKGROUND: The endoscopic diagnosis of depressed-type early gastric cancers is
      difficult because these cancers manifest as subtle changes in color and shape.
      The newly developed optimal band imaging (OBI) system can reconstruct the best
      spectral images derived from ordinary endoscopic images and enhances the mucosal
      surface without the use of dyes. This imaging technique is based on narrowing the
      bandwidth of conventional image arithmetically by using spectral estimation
      technology. OBJECTIVE: Evaluation of the usefulness of the OBI system for
      identifying the demarcation line of depressed-type early gastric cancers. DESIGN:
      Prospective study. SETTING: Jichi Medical University in Japan. PATIENTS: Twenty
      seven cases with depressed-type early gastric cancer. MAIN OUTCOME MEASUREMENT:
      Comparative study for the success rate of identifying the demarcation line of
      depressed-type early gastric cancer by using optimal band images and conventional
      endoscopic images. RESULTS: Demarcation of the depressed-type early gastric
      cancer was easily identified by optimal band images without magnification in 26
      of 27 cases (96%), because distinct demarcation was observed endoscopically
      between the reddish images of the cancerous lesion and the yellowish images of
      the surrounding noncancerous area. With 40-fold magnification of optimal band
      images, the demarcation was also clearly recognized in all cases. Medical
      students could point out the demarcation line with significantly greater accuracy
      by observing the new nonmagnified optimal band images than by the conventional
      images (P< .0001). LIMITATION: Small sample size. CONCLUSIONS: The new
      contrasting images of the OBI system can delineate the depressed-type early
      gastric cancer more easily than conventional endoscopy.

PMID- 18061597
TI  - EUS-guided FNA of regional lymph nodes in patients with unresectable hilar
      cholangiocarcinoma.
AB  - BACKGROUND: The clinical impact of EUS-guided FNA (EUS-FNA) in regional lymph
      node staging in patients with unresectable hilar cholangiocarcinoma before liver
      transplantation has yet to be determined. OBJECTIVES: To determine the frequency
      of regional lymph-node detection, identify EUS features predictive of benign or
      malignant lymph nodes, compare EUS lymph-node detection rates to CT/magnetic
      resonance imaging and exploratory laparotomy, and evaluate the impact of EUS-FNA
      on patient selection for liver transplantation. DESIGN: Retrospective case
      series. SETTING: Tertiary referral EUS unit. PATIENTS: Clinical, radiographic,
      EUS, cytologic, and surgical data of 47 patients with unresectable hilar
      cholangiocarcinoma before liver transplantation were evaluated. INTERVENTIONS:
      EUS-FNA. MAIN OUTCOME MEASUREMENTS: Lymph-node morphology and echo features.
      RESULTS: EUS identified lymph nodes in all patients. FNA of 70 lymph nodes
      identified metastases in 9 nodes of 8 patients (17%), who were then precluded
      from transplantation before a staging laparotomy. Identified lymph nodes,
      irrespective of malignant involvement, were typically oval and geographic in
      shape, of mixed echogenicity, with a hypoechoic border. There were no morphologic
      criteria or echo features to correlate with nodal malignancy. The EUS finding of
      absent regional lymph-node metastases was confirmed in 20 of 22 by a subsequent
      exploratory staging laparotomy. LIMITATIONS: Single institution, retrospective
      analysis. CONCLUSIONS: EUS identified lymph nodes in all patients, and
      confirmation of malignant lymph nodes detected by FNA precluded 17% of patients
      from transplantation. EUS-FNA of visualized lymph nodes irrespective of
      appearance is advised because morphology and echo features do not predict
      malignant involvement.

PMID- 18061598
TI  - Functional domains of the Toxoplasma GRA2 protein in the formation of the
      membranous nanotubular network of the parasitophorous vacuole.
AB  - Amphipathic alpha-helices have been proposed as the general means used by soluble
      proteins to induce membrane tubulation. Previous studies had shown that the GRA2
      dense granule protein of Toxoplasma gondii would be a crucial protein for the
      formation of the intravacuolar membranous nanotubular network (MNN) and that one
      of the functions of the MNN is to organise the parasites within the
      parasitophorous vacuole. GRA2 is a small protein (185 amino acids), predicted to
      contain three amphipathic alpha-helices (alpha1: 70-92; alpha2: 95-110 and
      alpha3: 119-139) when using the standard programs of secondary structure
      prediction. To investigate the respective contribution of each alpha-helix in the
      GRA2 functions, we used DeltaGRA2-HXGPRT knock-out complementation: eight
      truncated forms of GRA2 were expressed in the deleted recipient and the
      phenotypes of these mutants were analysed. This study showed that: (i) alpha3,
      when associated with the N-terminal region (NT) and the C-terminal region (CT),
      is sufficient to target the protein to the parasite posterior end and to induce
      formation of membranous vesicles within the vacuole. However, when associated
      only with CT, alpha3 is not sufficient to provide the hydrophobicity required for
      membrane association; (ii) the alpha1alpha2 region is alone not sufficient to
      induce membrane tubulation within the PV; and (iii) only one mutant, NT
      alpha1alpha2alpha3, restores most of the biochemical and functional properties of
      GRA2, including traffic to the dense granules, secretion into the vacuole,
      association with vacuolar membranes, induction of the MNN formation and
      organisation of the parasites within the vacuole.

PMID- 18061599
TI  - Effect of ski boot settings on tibio-femoral abduction and rotation during
      standing and simulated skiing.
AB  - Ski boots are designed to transfer high forces from the skier to the ski. For
      this purpose they are made of stiff materials and constrain the leg of the skier
      to an unnatural position. To overcome the problem of unnatural knee posture, the
      ski boots can be adjusted in the frontal plane as well as in the horizontal plane
      by the canting mechanism and the "v-position", respectively. Canting enables
      lateral and medial orientation of the shaft with respect to the base of the boot.
      The "v-position" is a pronounced outward rotation of the boot's base with respect
      to the ski's long axis. The purpose of this study is to investigate the effect of
      different foot rotations and ski boot canting settings on knee kinematics during
      standing and simulated skiing. Knee kinematics was measured by means of motion
      analysis and with the help of skin-mounted markers on 20 subjects. The ski boots
      in their standard settings significantly constrained the skier to an unnatural
      valgus position. Ski boot base rotation had a significant effect on internal
      external knee rotation, whereas canting had an effect on varus-valgus angles
      during standing. However, for the simulated skiing position no effects were
      observed. The study suggests that the constraints of the ski boots result in a
      clinically relevant valgus misalignment. Canting settings reduced the
      misalignment but only by about 10%. Increased ski boot canting settings would
      therefore be desirable. Knee kinematics showed that rotational misalignment could
      not be linked to any significant increase in injury risk.

PMID- 18061601
TI  - Characteristic fragmentation patterns of the trimethylsilyl and trimethylsilyl
      oxime derivatives of various saccharides as obtained by gas chromatography
      coupled to ion-trap mass spectrometry.
AB  - The fragmentation patterns of selected glycosidic linkage containing non-reducing
      (methylmannoside, methylgalactoside, lactitol, sucrose, trehalose, raffinose,
      erlose, melezitose) and reducing saccharides (maltose, cellobiose, lactose,
      melibiose, palatinose, primeverose, rutinose) have been compared as their
      trimethylsilyl and as their trimethylsilyl-oxime derivatives. Fragmentation
      characteristics of the glycosidic linkage containing trimethylsilyl-oxime
      derivatives have been investigated at the first time: these spectra are not
      available in the official libraries (NIST, Wiley). Applying gas chromatography
      ion trap mass spectrometry, informative fragments of high masses with high
      intensities have been obtained. Results confirmed characteristic differences
      between the simple trimethylsilyl derivative providing non-reducing glycosides
      and the trimethylsilyl, syn and antioxime species. Fragmentation starts at the
      glycosidic linkage resulting in the case of the non-reducing di- and
      trisaccharides in two, identical fragments of ring structure, with the abundant
      selective fragment ion at m/z=361. In the case of reducing disaccharides
      fragmentation provides two different moieties: one moiety of ring structure at
      m/z=361, and one of the open chain trimethylsilyl-oxime moiety with two special
      fragment ions at m/z=361 and at m/z=538. These fragmentation patterns proved to
      be independent on the position of the glycosidic linkage. Distribution of the
      selective fragment ions, obtained from their total ion current elutions, was
      evaluated on a quantitative basis, expressed in percentages of the total of ions
      formed. Reproducibility in the formation of these selective fragment ions,
      depending on their amount to be fragmented, proved to be proper for
      identification and quantitation purposes, equally. On this basis, in addition to
      the authentic ones, also two reducing disaccharides (primeverose and rutinose),
      as authentic compounds not available on the market, were identified and
      quantified in natural matrices.

PMID- 18061600
TI  - A three-dimensional model of the rat hindlimb: musculoskeletal geometry and
      muscle moment arms.
AB  - As a first step towards developing a dynamic model of the rat hindlimb, we
      measured muscle attachment and joint center coordinates relative to bony
      landmarks using stereophotogrammetry. Using these measurements, we analyzed
      muscle moment arms as functions of joint angle for most hindlimb muscles, and
      tested the hypothesis that postural change alone is sufficient to alter the
      function of selected muscles of the leg. We described muscle attachment sites as
      second-order curves. The length of the fit parabola and residual errors in the
      orthogonal directions give an estimate of muscle attachment sizes, which are
      consistent with observations made during dissection. We modeled each joint as a
      moving point dependent on joint angle; relative endpoint errors less than 7%
      indicate this method as accurate. Most muscles have moment arms with a large
      range across the physiological domain of joint angles, but their moment arms peak
      and vary little within the locomotion domain. The small variation in moment arms
      during locomotion potentially simplifies the neural control requirements during
      this phase. The moment arms of a number of muscles cross zero as angle varies
      within the quadrupedal locomotion domain, indicating they are intrinsically
      stabilizing. However, in the bipedal locomotion domain, the moment arms of these
      muscles do not cross zero and thus are no longer intrinsically stabilizing. We
      found that muscle function is largely determined by the change in moment arm with
      joint angle, particularly the transition from quadrupedal to bipedal posture,
      which may alter an intrinsically stabilizing arrangement or change the control
      burden.

PMID- 18061602
TI  - Development and validation of a liquid chromatography/electrospray ionization
      time-of-flight mass spectrometry method for relative and absolute quantification
      of steroidal alkaloids in Fritillaria species.
AB  - Steroidal alkaloids are naturally occurring nitrogen-containing compounds in many
      edible or medicinal plants, such as potato, tomato, Fritillaria and American
      hellebore, which possess a variety of toxicological and pharmacological effects
      on humans. The aim of this study is to explore the potential of liquid
      chromatography/electrospray ionization time-of-flight mass spectrometry (LC/ESI
      TOF-MS) method in the determination of these important alkaloids in plant
      matrices. The application of this method has been proven through 26 naturally
      occurring steroidal alkaloids in Fritillaria species. Accurate mass measurements
      within 4 ppm error were obtained for all the alkaloids detected out of various
      plant matrices, which allowed an unequivocal identification of the target
      steroidal alkaloids. The bunching factor for mass spectrometer, an important
      parameter significantly affecting the precision and accuracy of quantitative
      method, was firstly optimized in this work and satisfactory precision and
      linearity were achieved by the optimization of that parameter. The ranges of RSD
      values of intra-day and inter-day variability for all alkaloids were decreased
      remarkably from 41.8-159% and 13.2-140% to 0.32-7.98% and 2.37-16.1%,
      respectively, when the value of bunching factor was optimized from 1 to 3.
      Linearity of response more than two orders of magnitude was also demonstrated
      (regression coefficient >0.99). The LC/TOF-MS detection method offered
      improvements to the sensitivity, compared with previously applied LC (or GC)
      methods, with limits of detection down to 0.0014-0.0335 microg/ml. The results in
      this paper illustrate the robustness and applicability of LC/TOF-MS for steroidal
      alkaloids analysis in plant samples. In addition, relative quantitative
      determination of steroidal alkaloid with one popular analyte verticinone which is
      commercially available was also investigated in order to break through the choke
      point of lack of standards in phytochemical analysis. The accuracies of relative
      quantitative method for steroidal alkaloids determinations with verticinone were
      90.6-110.0% (average 98.5%) suggesting that it is feasible to quantify steroidal
      alkaloids by the proposed relative quantitative determination method within
      acceptable errors.

PMID- 18061603
TI  - Modified fractal model and rheological properties of colloidal networks.
AB  - The scaling relationship between the storage modulus (G(')) and the volume
      fraction of solids (Phi) in fat crystal networks has been explained by the
      fractal model developed by our group. However, many experimental results and
      simulation studies suggest that the stress distribution within a colloidal
      network is dramatically heterogeneous, which means that a small part of the
      network carries most of the stress, while the other part of the network does not
      contribute much to the elastic properties of the system. This concept was
      introduced into a modified fractal model. The volume fraction of solids term
      (Phi) in the original fractal model was replaced by Phi(e), the effective volume
      fraction of solids, in the modified fractal model, which represents the volume
      fraction of stress-carrying solids. A proposed expression for Phi(e) is given and
      a modified expression for the scaling relationship between G(') and Phi is
      obtained. The modified fractal model fits the experiment data well and
      successfully explains the sometimes observed nonlinear log-log behavior between
      the storage modulus of colloidal networks and their volume fraction of solids.

PMID- 18061604
TI  - Petroleum resins adsorption onto quartz sand: near infrared (NIR) spectroscopy
      study.
AB  - In this paper we have tried to evaluate adsorption parameters of petroleum
      resins. Near infrared (NIR) spectroscopy is applied for resins bulk concentration
      evaluation during adsorption process. NIR experimental scheme and parameters are
      provided. NIR spectra range of 9000-13,000 cm(-1) is chosen. Quartz sand (0.2-0.8
      mm fraction) is used as adsorbent; benzene is used as solvent. Different
      approaches of "NIR spectra-resins concentration" calibration model building are
      discussed. Partial least squares (PLS) regression method is used. Langmuir model
      is chosen for experimental data fitting. Combined usage of kinetic and isothermic
      data gives us ability to evaluate the maximal adsorbed mass density, the
      equilibrium constant of adsorption, and the rate constants of adsorption (and
      desorption). The rate constants of resins adsorption and desorption are found to
      be concentration independent.

PMID- 18061605
TI  - Detection of hydrophobic microdomains in anionic polyelectrolytes with tris-(4,7
      diphenyl-1,10-phenanthroline)3Cr(III).
AB  - This paper describes the changes in the luminescent properties of the tris-(4,7
      diphenyl-1,10-phenanthroline)(3)Cr(III), [Cr(dip)(3)](3+) complex in an aqueous
      solution of three polyelectrolytes containing cyclohexyl, phenyl or 1-naphthyl
      groups in the side chain. When the polyelectrolytes form hydrophobic microdomains
      the luminescence of [Cr(dip)(3)](3+) is affected. The luminescence increases in
      the presence of cyclohexyl groups in the side chains, but decreases in the
      presence of phenyl and naphthyl groups (in that order). This fact can be
      explained in terms of a reductive quenching mechanism between the complex and the
      aromatic groups. Indeed, experiments performed with the complex and the alcohols
      corresponding to the functional groups, i.e., cyclohexanol, phenol, and naphthol,
      also show the same behavior, confirming the interaction with the functional
      groups and not other components of the polyelectrolyte. The luminescent
      properties of the [Cr(dip)(3)](3+) complex allow the detection of hydrophobic
      microdomains arising from the host-guest interaction. Moreover, the complex is
      able to distinguish between a nonaromatic hydrophobic microdomain and an aromatic
      one.

PMID- 18061606
TI  - Tuning the hydrophobic properties of silica particles by surface silanization
      using mixed self-assembled monolayers.
AB  - Here we describe a novel method of preparing hydrophobic silica particles (100
      150 nm; water contact angle of dropcasted film ranging from 60 degrees to 168
      degrees) by surface functionalization using different alkyltrichlorosilanes.
      During their preparation, the molecular surface roughness is also concurrently
      engineered facilitating a change in both the surface chemical composition and the
      geometrical microstructure to generate hierarchical structures. The water contact
      angle has been measured on drop-cast film surface. The enhancement in the water
      contact angle on 3D (curved) SAMs in comparison to that on 2D (planar) surface is
      discussed using the Cassie-Baxter equation. These silica particles can be
      utilized for many potential applications including selective adsorbents and
      catalysts, chromatographic supports and separators in microfluidic devices.

PMID- 18061607
TI  - Evidence of direct crystal growth and presence of hollow microspheres in
      magnetite particles prepared by oxidation of Fe(OH)2.
AB  - We provide new information relevant to the crystallinity and growth mechanism of
      magnetite particles that were fabricated following the method of Sugimoto and
      Matijevic [J. Colloid Interface Sci. 74 (1980) 227]. These authors observed that
      in a small excess of Fe(2+), particles grew by aggregation and recrystallization
      of smaller units, so that until now the resulting particles were thought to be
      polycrystalline. With the help of transmission electron microscopy (TEM) and
      selected area electron diffraction (SAED), we also detected the presence of
      monocrystalline particles, which are strong evidence of the occurrence of direct
      crystal growth. This growth mechanism seems to coexist with that of the
      aggregation of primary units proposed by Sugimoto and Matijevic. Careful
      examination of electron microscopy micrographs also revealed the presence of many
      hollow polycrystalline microspheres.

PMID- 18061609
TI  - Children's false memory and true disclosure in the face of repeated questions.
AB  - The current study was designed to investigate children's memory and
      suggestibility for events differing in valence (positive or negative) and
      veracity (true or false). A total of 82 3- and 5-year-olds were asked repeated
      questions about true and false events, either in a grouped order (i.e., all
      questions about a certain event asked consecutively) or in a nongrouped order
      (i.e., questions about a certain event were interspersed with questions about
      other events). Interviewer gender was also varied. Individual differences,
      including attachment style, inhibition, and behavioral adjustment, were examined
      as potential predictors of memory and suggestibility. Results revealed
      significant age, valence, and veracity effects on children's memory reports. Path
      analysis demonstrated that individual differences in behavioral problems and
      inhibitory ability predicted children's provision of inaccurate information.
      Implications for psychological theory and legal application are discussed.

PMID- 18061608
TI  - Retinal cell types are differentially affected in sheep with scrapie.
AB  - Transmissible spongiform encephalopathies (TSEs) are a group of fatal
      neurodegenerative diseases characterized microscopically by spongiform lesions
      (vacuolation) in the neuropil, neuronal loss, and gliosis. Accumulation of the
      abnormal form of the prion protein (PrP(Sc)) has been demonstrated in the retina
      of natural and non-natural TSE-affected hosts, with or without evidence of
      microscopically detectable retinal pathology. This study was conducted to
      investigate the effect of PrP(Sc) accumulation on retinal neurons in a natural
      host lacking overt microscopical evidence of retinal degeneration by comparing
      the distribution of retinal cell type-specific markers in control and scrapie
      affected sheep. In retinas with PrP(Sc)-immunoreactivity, there was disruption of
      the normal immunoreactivity patterns of the alpha isoform of protein kinase C
      (PKCalpha) and vesicular glutamate transporter 1 (VGLUT1), markers of retinal
      bipolar cells. Altered immunoreactivity was also observed for microtubule
      associated protein 2 (MAP2), a marker of a subset of retinal ganglion cells, and
      glutamine synthetase (GS), a marker of Muller glia. These results demonstrate
      alterations of immunoreactivity patterns for proteins associated with specific
      cell types in retinas with PrP(Sc) accumulation, despite an absence of
      microscopical evidence of retinal degeneration.

PMID- 18061610
TI  - Hepatitis B vaccine-specific CD4(+) T cells can be detected and characterised at
      the single cell level: limited usefulness of dendritic cells as signal enhancers.
AB  - Hepatitis B surface antigen (HBsAg)-specific T cells were analysed in 16 healthy
      individuals vaccinated against hepatitis B, using optimised protocols. HBsAg
      specific IFN-gamma producing CD4(+) T cells were found at a similar low frequency
      (0.01%) within the naive T cell subset, the central and the effector memory T
      cell subset. Overall, HBsAg-specific total CD4(+) T cells were detected in
      approximately 81% of the HBV vaccinees. The use of dendritic cells substantially
      increased the otherwise low proliferative responses but not the percentage of IFN
      gamma producing cells. The analysis of readily detectable CMV-specific CD4(+) T
      cell responses was used as a positive control and confirmed the adequacy of our
      assays. T cell responses associated with (in-) adequate hepatitis B vaccination
      can now be analysed in more detail.

PMID- 18061611
TI  - Comparison of intracoronary and transendocardial delivery of allogeneic
      mesenchymal cells in a canine model of acute myocardial infarction.
AB  - This study assessed safety of transendocardial (TE) electromechanical-guided
      delivery of bone marrow mesenchymal stem cells (MSCs) after acute myocardial
      infarction (AMI) and compared intracoronary (IC) delivery with TE delivery. In a
      canine acute myocardial ischemia model, 100 x 10(6) MSCs were delivered 7 days
      after AMI via IC and TE routes. Functional assessment was performed by 2D
      echocardiogram, and detailed histopathologic analyses were performed to assess
      the impact of cell therapy in vascular density and fibrosis. Patterns of cell
      distribution in both delivery methods were also compared. There was a
      statistically significant reduction in the amount of myocardial ischemia in the
      TE group (P=0.007). Left ventricular ejection fraction (LVEF) increased 13%
      (mean) in the TE group (21-day follow-up) and was significantly better than that
      of the controls (P=0.01), but did not improve in the IC-delivery group.
      Dissimilar patterns of cell distribution were noted between the IC and TE groups.
      This study suggests that MSC treatment is probably safe and effective after AMI.
      In the comparison of TE and IC delivery, the TE group showed higher cell
      retention (clusters even in the injury center of the infarct) with an increased
      vascularity and greater functional improvement than did the IC group (no
      clusters; cells at the border of the infarct). The higher local cell density in
      the TE group may be important for therapeutic effectiveness.

PMID- 18061612
TI  - Effect of phosphorylation on alpha B-crystallin: differences in stability,
      subunit exchange and chaperone activity of homo and mixed oligomers of alpha B
      crystallin and its phosphorylation-mimicking mutant.
AB  - Phosphorylation appears to be one of the modulators of chaperone functions of
      small heat shock proteins. However, the role of phosphorylation is not completely
      understood. We have investigated the structural and functional consequences of a
      phosphorylation-mimicking mutation in alpha B-crystallin, a small heat shock
      protein with chaperone activity. We have used a phosphorylation-mimicking mutant,
      3D alpha B-crystallin, in which all the three phosphorylatable serine residues
      are replaced with aspartic acid. 3D alpha B-Crystallin showed enhanced chaperone
      like activity towards DTT-induced aggregation of insulin, heat-induced
      aggregation of citrate synthase and SDS-induced amyloid fibril formation of alpha
      synuclein. Fluorescence and circular dichroism spectroscopic studies showed that
      3D alpha B-crystallin exhibits lower stability towards urea-induced denaturation
      compared to alpha B-crystallin. Subunit exchange studies using fluorescence
      resonance energy transfer showed that 3D alpha B-crystallin exhibits an
      observable increase in subunit exchange compared to alpha B-crystallin. Since
      only part of alpha B-crystallin is phosphorylated in vivo, our subunit exchange
      studies indicate that formation of mixed oligomers between the unphosphorylated
      and phosphorylated subunits are likely to play a role in vivo. Our study shows
      that mixed-oligomer formation modulates the chaperone-like activity. We propose
      that the degree of phosphorylation of the alpha B-crystallin oligomers and
      temperature are key modulators to achieve a wide range of chaperone capabilities
      of the small heat shock protein, alpha -crystallin.

PMID- 18061613
TI  - Structural studies on the second Mycobacterium smegmatis Dps: invariant and
      variable features of structure, assembly and function.
AB  - A second DNA binding protein from stationary-phase cells of Mycobacterium
      smegmatis (MsDps2) has been identified from the bacterial genome. It was cloned,
      expressed and characterised and its crystal structure was determined. The core
      dodecameric structure of MsDps2 is the same as that of the Dps from the organism
      described earlier (MsDps1). However, MsDps2 possesses a long N-terminal tail
      instead of the C-terminal tail in MsDps1. This tail appears to be involved in DNA
      binding. It is also intimately involved in stabilizing the dodecamer. Partly on
      account of this factor, MsDps2 assembles straightway into the dodecamer, while
      MsDps1 does so on incubation after going through an intermediate trimeric stage.
      The ferroxidation centre is similar in the two proteins, while the pores leading
      to it exhibit some difference. The mode of sequestration of DNA in the
      crystalline array of molecules, as evidenced by the crystal structures, appears
      to be different in MsDps1 and MsDps2, highlighting the variability in the mode of
      Dps-DNA complexation. A sequence search led to the identification of 300 Dps
      molecules in bacteria with known genome sequences. Fifty bacteria contain two or
      more types of Dps molecules each, while 195 contain only one type. Some bacteria,
      notably some pathogenic ones, do not contain Dps. A sequence signature for Dps
      could also be derived from the analysis.

PMID- 18061614
TI  - Development of a reliable non-union model in mice.
AB  - BACKGROUND: Despite the growing knowledge of the mechanisms of fracture healing,
      non-unions remain a substantial clinical problem. There is increasing interest in
      murine fracture models because they would allow studying molecular mechanisms of
      healing with the help of specific antibodies and gene-targeted animals. However,
      until now it has not been possible to reproducibly create non-unions in mice.
      Thus, the aim of this study was to develop a reliable non-union model in mice.
      METHODS: After creating segmental defects of 0.8 mm and 1.8 mm, mice femora were
      stabilized with a pin-clip fixation. Additionally, the influence of periosteal
      resection on the development of non-unions was studied. Histological and
      radiological healing was analyzed 5, 10, and 15 wk after surgery. RESULTS: After
      10 wk all animals showed poor healing with predominantly atrophic non-unions.
      Whereas the 0.8 mm and the 1.8 mm gap with intact periosteum showed
      radiologically in 4/6 and 3/6 cases possible healing, only the gap of 1.8 mm with
      additional periosteal resection resulted in 100% (6/6) non-unions. The non-unions
      were confirmed also after 15 wk and appeared atrophic with typical histological
      and radiological features. These included lack of fracture bridging with abundant
      fibrous tissue in the gap, absence of callus formation, and rounded bone ends. Of
      interest, the non-unions were not avascular, but demonstrated a considerable
      vascularity within the fibrous tissue. CONCLUSION: Taken together, we herein
      demonstrate for the first time a reliable non-union model in mice. This allows us
      to study molecular aspects of non-union formation and analyze different
      therapeutical strategies in these animals.

PMID- 18061615
TI  - Donor preconditioning with taurine protects kidney grafts from injury after
      experimental transplantation.
AB  - BACKGROUND: Ischemia/reperfusion injury is a major problem in clinical
      transplantation (Tx). Taurine has been shown to protect liver grafts from
      ischemia/reperfusion injury after Tx. Thus, this study was designed to evaluate
      its effect on kidney grafts after transplantation. MATERIALS AND METHODS: Various
      concentrations of taurine were infused before donor nephrectomy (1.5 mL; 30, 100,
      300 mM). Controls were given the same volume of Ringers' solution. Subsequently,
      grafts were cold-stored for 19 h in histidine-tryptophan-ketoglutarate solution
      and transplanted. Six hours after Tx, graft function and injury were assessed
      with blood urea nitrogen/creatinine and aspartate aminotransferase/lactate
      dehydrogenase. Graft biopsies were taken to evaluate tubular damage, caspase-3,
      superoxide dismutase, and heat shock protein 72 (HSP-72) to index necrosis,
      apoptosis, antioxidative capacity, and regeneration, respectively. RESULTS:
      Taurine significantly decreased blood urea nitrogen, creatinine, aspartate
      aminotransferase, and lactate dehydrogenase in a dose-dependent manner to up to
      71%, 69%, 51%, and 53% of controls, respectively. Further, tubular damage and
      caspase-3 expression decreased to 44% and 18% of control values (P < 0.01), while
      superoxide dismutase and heat shock protein 72 expression increased by 95% and
      77% of controls, respectively (P < 0.05). CONCLUSIONS: This study demonstrates
      that donor preconditioning with taurine protects kidney grafts from injury
      (apoptosis, necrosis), improves graft function, and increases the regenerative
      potential most likely via mechanisms including antioxidation.

PMID- 18061616
TI  - Apoptosis-inducing factor and colon cancer.
AB  - Programmed cell death is a fundamental requirement for embryogenesis, organ
      metamorphosis, and tissue homeostasis. Since the vast majority of cytotoxic
      modalities exert their anti-tumor effects by induction of apoptosis, programmed
      cell death has emerged as a potential target for cancer treatment at various
      stages of tumor progression. Immuno-regulation and chemoradiosensitization are
      potential pathways where insight in apoptotic mechanisms may lead to improvement
      of chemoradiotherapeutic modalities. The central mediator of the intrinsic
      pathway of apoptosis is the mitochondrion, in which changes of the outer
      membrane's permeability cause an outflow of cytochrome c and more than 40
      molecules involved in apoptosis. These include Smac/DIABLO, Omi/HTR A2,
      endonuclease G, and apoptosis inducing factor (AIF). AIF, a 57 kDa mitochondrial
      oxidoreductase, is released into the cytoplasm and translocates to the nucleus to
      induce cell death in response to poly-(ADP-ribose) polymerase-1 activation,
      resulting is DNA fragmentation independent of caspase activation. As a caspase
      independent mechanism of apoptosis, AIF may be a potential target for
      chemoradiotherapeutic intervention in a number of malignancies. The aim of this
      review is to provide the available evidence of the role AIF in several
      malignancies with a particular emphasis in colon carcinogenesis.

PMID- 18061617
TI  - Excessive inflammation but decreased immunological response renders liver
      susceptible to infection in bile duct ligated mice.
AB  - BACKGROUND/AIMS: Obstructive jaundice (OJ) is associated with increased surgical
      morbidity and infectious complication. The aim of the current study was to
      clarify the mechanism of excessive inflammation and susceptibility to infection
      in OJ. METHODS: C57/BL6 mice were subjected to bile duct ligation (BDL) or sham
      surgery. Expression tumor necrosis factor-alpha, macrophage inflammatory protein
      2, monocyte chemoattractant protein-1, inducible protein-10, and interleukin (IL)
      10, activation of nuclear factor kappa B, fluorescence activated cell sorter
      analysis, serum alanine aminotransferase levels, and histology were examined.
      Survival after lipopolysaccharide (LPS) administration or cecal ligation and
      puncture 3 or 14 d after surgery was determined. IL-1beta and interferon-gamma
      expression was examined after LPS administration. RESULTS: OJ induced nuclear
      factor kappa B activation and increased expression of macrophage inflammatory
      protein-2, which caused significant increases in neutrophil recruitment. Serum
      alanine aminotransferase levels increased consistent with histological
      observations in OJ. Mononuclear cells were recruited in the liver after BDL
      associated with monocyte chemoattractant protein-1 up-regulation. The recruitment
      of NK and T cells was varied, consistent with IP-10 expression during the time
      course of OJ. IL-10 expression was significantly up-regulated 14 d after BDL.
      After LPS administration, the mice at 3 d after BDL and at 3 and 14 d after sham
      surgery were all still alive, but all mice at 14 d after BDL died. After LPS
      administration, IL-1beta significantly increased in the mice at 14 d after BDL.
      CONCLUSIONS: Immune response such as expression of pro- and anti-inflammatory
      mediators and recruitment of immune cells may thus differ over the time course of
      OJ. Prolonged OJ may cause excessive inflammation, thus result in susceptibility
      to infection.

PMID- 18061618
TI  - Confirmation and extension of the validity of the Multiple Sclerosis Walking
      Scale-12 (MSWS-12).
AB  - OBJECTIVE: The Multiple Sclerosis Walking Scale-12 (MSWS-12) is a 12-item patient
      rated measure of the impact of MS on walking. As validation of scores from a
      measure is an ongoing and evolving process, the provision of additional evidence
      is warranted that confirms and extends the validity of inferences from scores on
      the MSWS-12. METHOD: Participants (N=133) were recruited through support group
      meetings of the Greater Illinois and Indiana State Chapters of the National
      Multiple Sclerosis Society, and wore an accelerometer for a seven-day period and
      completed the MSWS-12 and other outcome measures. RESULTS: Confirmatory factor
      analysis indicated that a single-factor model provided an adequate fit for MSWS
      12 scores. MSWS-12 scores demonstrated strong evidence of internal consistency.
      The correlations between MSWS-12 scores with scores from other scales, including
      an accelerometer, were consistent with our a priori hypotheses. CONCLUSION: We
      provide evidence that both confirms and extends the validity of inferences from
      scores of the MSWS-12 as a measure of the impact of MS on walking in a community
      based sample of individuals with MS.

PMID- 18061619
TI  - Oxidative-stress-induced apoptosis in PBLs of two patients with Parkinson disease
      secondary to alpha-synuclein mutation.
AB  - Alpha-synuclein has been implicated in the pathology of certain neurodegenerative
      diseases, including Parkinson disease (PD). Although the precise physiological
      and pathological role of alpha-synuclein is unclear, overexpression of the
      protein or its mutants may reduce cell viability. In this study we evaluated the
      apoptotic response to oxidative stress induced by 2-deoxy-d-ribose (dRib) in
      peripheral blood lymphocytes (PBLs) of two siblings with Parkinson disease
      secondary to A53T alpha-synuclein mutation. PBLs exposed to oxidative stress
      showed a higher percentage of apoptotic cells in PD patients than in controls.
      However in cells of PD patients, the increase of apoptotic response was lower
      than in controls, suggesting that cells of PD patients have greater "resistance"
      to oxidative stress. We conclude that other environmental agents could play a key
      role in inducing programmed cell death in cells of PD patients with mutant alpha
      synuclein.

PMID- 18061620
TI  - Monte Carlo simulation of a simple gene network yields new evolutionary insights.
AB  - Monte Carlo simulations of a genetic toggle switch show that its behavior can be
      more complex than analytic models would suggest. We show here that as a result of
      the interplay between frequent and infrequent reaction events, such a switch can
      have more stable states than an analytic model would predict, and that the number
      and character of these states depend to a large extent on the propensity of
      transcription factors to bind to and dissociate from promoters. The effects of
      gene duplications differ even more; in analytic models, these seem to result in
      the disappearance of bi-stability and thus a loss of the switching function, but
      a Monte Carlo simulation shows that they can result in the appearance of new
      stable states without the loss of old ones, and thus in an increase of the
      complexity of the switch's behavior which may facilitate the evolution of new
      cellular functions. These differences are of interest with respect to the
      evolution of gene networks, particularly in clonal lines of cancer cells, where
      the duplication of active genes is an extremely common event, and often seems to
      result in the appearance of viable new cellular phenotypes.

PMID- 18061621
TI  - A deterministic model for the processing and presentation of bacteria-derived
      antigenic peptides.
AB  - The amount and the dynamics of antigen supply to the cellular antigen processing
      and presentation machinery differ largely among diverse microbial antigens and
      various types of antigen presenting cells. The precise influence, however, of
      antigen supply on the antigen presentation pattern of cells is not known. Here,
      we provide a basic deterministic mathematical model of antigen processing and
      presentation of microbial antigens. The model predicts that different types of
      antigen presenting cells e.g. cells presenting or cross-presenting exogenous
      antigens, cells infected with replicating microbes, or cells in which microbial
      antigen synthesis is blocked after a certain period of time have inherently
      different antigen presentation patterns which are defined by the kinetics of
      antigen supply. The reevaluation of existing experimental data [Sijts, A.J.,
      Pamer, E.G., 1997. Enhanced intracellular dissociation of major
      histocompatibility complex class I-associated peptides: a mechanism for
      optimizing the spectrum of cell surface-presented cytotoxic T lymphocyte
      epitopes. J. Exp. Med. 185, 1403-1411] describing the processing and presentation
      of two antigenic peptides derived from the p60 proteins of the facultatively
      intracellular bacterium Listeria monocytogenes shows that p60 proteins
      accumulating intracellularly during bacterial infection of cells play no
      measurable role as substrate for the cytosolic antigen presentation pathway.

PMID- 18061622
TI  - Mental stress induces sustained elevation of blood pressure and lipid
      peroxidation in postmenopausal women.
AB  - Mental stress is thought to underlie cardiovascular events, but there is
      information on oxidative stress induced by mental stress in association with
      cardiovascular responses in women. Using a sensitive assay for plasma 4-hydroxy-2
      nonenal (HNE), as a marker for oxidative stress, we addressed the relation
      between pressor responses and oxidative stress induced by mental or physical
      stress in premenopausal and postmenopausal women. Healthy subjects (7
      postmenopausal and 8 premenopausal women, in early and late follicular phases)
      were subjected to mental and physical stress evoked by a Color Word Test (CWT)
      and isometric handgrip, respectively. The CWT induced a rapid elevation of
      diastolic blood pressure (DBP), at a higher level in the postmenopausal than in
      the premenopausal women (p<0.01), and this higher DBP was sustained during the
      CWT and recovery (p<0.01). The CWT induced a significant elevation in plasma
      noradrenaline in premenopausal women in the early follicular phase and in
      postmenopausal women (p<0.05). Plasma nitric oxide metabolites were higher in
      postmenopausal than in the premenopausal women in the late follicular phase
      (p<0.05), but did not change during exposure to the two types of stress in either
      group. Plasma HNE was increased during recovery from the CWT, but not the
      handgrip, in postmenopausal women (2.4 times, p<0.05). There was a significant
      difference in the time course of the CWT-induced HNE response between the
      postmenopausal and premenopausal women (p<0.05). These findings suggest that
      mental, but not physical, stress causes sustained diastolic blood pressure
      elevation in postmenopausal women, accompanied by heightened oxidative stress.

PMID- 18061623
TI  - Development of a fluorescent antibody method for the detection of Enterococcus
      faecium and its potential for coastal aquatic environment monitoring.
AB  - A direct, microscopic fluorescent antibody method was developed to detect the
      occurrence of Enterococcus faecium in coastal aquatic environments and was
      compared with the conventional membrane filtering method. The "in situ"
      application of the antibody-based protocol in the analysis of water samples
      collected from coastal polyhaline habitats demonstrated good sensitivity and ease
      of implementation. Data obtained with the microscopic technique were in agreement
      with those obtained from culture counts. The fluorescent antibody method proved
      to be a rapid and reliable technique for the detection of E. faecium. The
      advantages and limitations intrinsic to the method are discussed, highlighting
      the potential of this new technique for monitoring coastal aquatic environments.

PMID- 18061624
TI  - Spatio-temporal changes of marine macrobenthic community in sub-tropical waters
      upon recovery from eutrophication. II. Life-history traits and feeding guilds of
      polychaete community.
AB  - A two-year study was conducted in the vicinity of a harbour in sub-tropical Hong
      Kong, to examine the progress of recovery of macrobenthic community, based on
      analyses of both life-history traits and trophic guilds of polychaetes, upon
      cessation of organic pollution caused by sewage discharge. Seventy seven out of
      83 species collected were classified under four ecological groups based on the
      life-history traits and sensitivity to organic gradients. The mean ATZI marine
      biotic index (AMBI) derived from these ecological groups showed spatial
      difference among the five sampling locations. In particular, the presence of
      different percentages of polychaete species from Groups III (unbalanced
      community) and IV (polluted community) suggested the presence of pollution stress
      in certain degree at all sampling locations. However, no significant temporal
      changes were noted over the study period. From all polychaete species identified,
      they were classified into 13 feeding guilds. The mean diversity of these feeding
      guilds at most of the sampling locations was significantly higher than that at
      one of the inside-harbour locations. The composition of feeding guilds was also
      significantly different spatially. At one of the inside-harbour locations, the
      dominant feeding guilds were motile/discretely motile surface deposit feeders
      with tentaculates or unarmed pharynx, and motile omnivores with jawed pharynx in
      the first year of study, but were replaced by motile, jawed carnivores in the
      second year of study. The increased proportion of carnivores over the study
      period can be seen as a sign of recovery in the community structure since
      abundance of predators is commonly higher in habitats with better environmental
      quality. The implications of using life-history traits and feeding guild analyses
      for benthic community are discussed.

PMID- 18061625
TI  - The Caulerpa racemosa invasion: a critical review.
AB  - Caulerpa racemosa var. cylindracea is a marine Chlorophyta introduced into the
      Mediterranean Sea from south-western Australia. Since 1990, it has been invading
      the Mediterranean Sea and the Canary Islands, raising ecological problems.
      Although this invasion event can be considered as one of the most serious in the
      history of species introduced into the Mediterranean Sea, C. racemosa has not
      triggered as much attention as the famous "killer alga"Caulerpa taxifolia. The
      aim of the present study was: (i) to summarize the current state of knowledge
      with regard to the distribution, the various biological and ecological
      characteristics of the introduced C. racemosa and its impact on the Mediterranean
      coastal environment; (ii) to discuss the various hypotheses regarding the
      explanation for its rapid and successful spread; (iii) to investigate the
      disparity in the treatment of C. racemosa and Caulerpa taxifolia invasions; and
      (iv) to outline future research needs.

PMID- 18061626
TI  - Total mercury body burden in Pacific harbor seal, Phoca vitulina richardii, pups
      from central California.
AB  - To determine body and tissue compartment-specific burdens (mg) of total mercury
      (THg), tissues were weighed and analyzed for THg concentration (microg/g fw) in
      Pacific harbor seal (Phoca vitulina richardii) pups from central California in
      2006. THg concentrations were related as follows: hair >> liver = kidney = pelt >
      muscle > other = heart > brain > blubber > bone. THg burden, however, was related
      as: pelt = muscle > liver = other > kidney = blubber > brain = heart > bone. THg
      concentration and burden in muscle were strongly associated with delta(15)N.
      delta(13)C and delta(15)N values were significantly greater in muscle than liver,
      and delta(13)C was significantly lesser the longer animals were in
      rehabilitation. Because THg concentration and burden in muscle correlated most
      significantly with other tissue compartments, we recommend that muscle from the
      specific sites we sampled be used instead of liver or hair for biomonitoring THg
      in harbor seals. Assessment of proportional THg burdens within each tissue
      compartment for harbor seals pups included use of a conceptual model, allowing
      for more complete visual characterization of THg body burden.

PMID- 18061627
TI  - Spatio-temporal changes of marine macrobenthic community in sub-tropical waters
      upon recovery from eutrophication. I. Sediment quality and community structure.
AB  - A two-year study was conducted in the vicinity of a harbour in sub-tropical Hong
      Kong, to examine the progress of improvement in sediment quality and recovery of
      macrobenthic community upon cessation of organic pollution caused by sewage
      discharge. Median sediment particle diameter (Mdphi) and levels of total organic
      carbon (TOC), total Kjeldahl nitrogen (TKN), ammonia-nitrogen (NH(3)-N) and total
      phosphorus (TP), as well as macrobenthic species composition and abundance were
      determined bi-monthly at three inside-harbour and two outside-harbour locations.
      At the two inside-harbour locations, significantly higher levels of TOC, TKN,
      NH(3)-N and TP in sediments were observed than the outside-harbour locations.
      However, no significant temporal change of nutrient levels was detected at all
      sampling locations during the two-year study, except a significant decrease in
      TKN and NH(3)-N levels at one outside-harbour location and a decline in NH(3)-N
      content at another outside-harbour location. Spatially, the highest in mean total
      species number, individual number, species diversity H' and lowest evenness J was
      found at one outside-harbour location, whereas the other four locations had
      relatively similar values. H' was negatively correlated with TOC, TKN, NH(3)-N
      and TP content in sediments while J was positively correlated with MDphi. Across
      the study period, the patterns of macrobenthic community were significantly
      different among all samplings and that the spatial difference of benthic
      community was best correlated with MDphi, TOC, TKN and water depth. A weak sign
      of recovery in macrobenthic community structure was detected at inside-harbour
      locations, with replacement of opportunistic by ubiquitous species over the two
      year study. The slow recovery of macrobenthic community was related to sediment
      characteristics. Results of a larval settlement bioassay using the polychaete
      Capitella sp. I also demonstrated that the inside-harbour sediments were still
      unfavourable for colonization and larval settlement of species sensitive to
      pollution. The slow biodegradation of the organic pollutants and continuous
      presence of heavy metals in the sediment may hinder settlement and colonization
      of benthic animals. However, increases of H' and J were observed in a longer time
      scale when comparing the present data with those obtained four years ago. This
      suggested that a detectable recovery of benthic community in the harbour may take
      at least three years and a complete recovery may even take longer duration.

PMID- 18061628
TI  - [Effectiveness of adjuvant corticosteroid therapy for chronic subdural hematoma:
      a retrospective study of 198 cases].
AB  - BACKGROUND AND PURPOSE: Adjuvant treatments can be proposed in addition to
      surgery for patients with chronic subdural hematoma (CSDH) in order to improve
      the postoperative outcome. According to the survey published in 2001 by the
      Neurosurgery French Society, 38% of French neurosurgeons use adjuvant
      corticosteroid therapy after surgery. Does this adjuvant corticosteroid therapy
      have an effect on the postoperative outcome of CSDH? METHODS: A retrospective
      trial was performed on patients who were surgically treated for CSDH between
      January 1998 and July 2002 in the Nice Department of Neurosurgery. Corticosteroid
      therapy was initiated just after surgery and maintained for one month. Part of
      the patients were not given corticosteroids enabling a comparison of two groups:
      "corticosteroid therapy" versus "no corticosteroid therapy". RESULTS: One hundred
      and ninety-eight patients were included in the trial, 142 patients in the
      "corticosteroid therapy" group and 56 patients in the "no corticosteroid therapy"
      group. The difference in survival between the two groups was significant in favor
      of the group give corticosteroids. A multivariate analysis was carried out which
      confirmed the beneficial effect of the corticosteroid therapy on survival of the
      operated patients. Their risk of death was threefold less than those not given
      this treatment (p=0.006). CONCLUSIONS: This study highlighted a protective effect
      of postoperative corticosteroid therapy on patient survival. This effect
      persisted at multivariate analysis. However, due to skews inherent in
      retrospective studies, a multicentric prospective randomized trial is being
      prepared in our institution to confirm these results.

PMID- 18061629
TI  - [Frontal giant cell glioblastoma: radio-induced tumor? Case report and literature
      review].
AB  - The current WHO classification recognizes two distinct variants of glioblastoma
      multiforme (GBMs): giant cell glioblastoma (GCG) and gliosarcoma, based on
      histological heterogeneity. Unlike conventional GBMs, GCGs preferentially occur
      in younger individuals and are associated with a better prognosis, a few reports
      documenting prolonged survival up to 17 years after diagnosis. However,
      transformation to gliosarcoma is possible and has been already reported. Radio
      induced glioblastoma, which meets Cahan's criteria for radio-induced tumor, is
      very rare; the first case was published by Kleriga et al. We report a rare case
      observed in a 46-year-old man with a past history of right nose leiomyosarcoma
      treated 40 years earlier by surgery and interstitial and external beam radiation.
      At admission, the patient presented left hemiparesis revealing a right frontal
      GCG confirmed by pathology after cranial surgery. We describe this case firstly
      because of its rare histological variety and discuss its clinical, radiological,
      histopathological, therapeutic and prognostic characteristics with literature
      data. Secondly, because of its occurrence 40 years after external radiotherapy,
      which could suggest the hypothesis of radio-induced glioblastoma.

PMID- 18061630
TI  - [Cranial vault chondroma: a case report and literature review].
AB  - Intracranial chondromas are unusual tumors, which most commonly arise from
      cartilage rets in the synchondrosis at the base of the skull. They are most
      likely found in the sellar and parasellar regions, usually located extradurally.
      In rare instances, these tumors originate from the dura mater of the convexity.
      In these cases their neuroradiological features may mimic other intracranial
      tumors. We present the case of a 50-year-old male presenting a large parasagittal
      tumor originating in the frontal convexity. MRI-scans revealed a cavitated tumor
      strongly enhanced after gadolinium infusion mimicking a parasagittal meningioma.
      There was no obstruction of the superior sagittal sinus as shown by cerebral
      angiogram. Total excision was achieved and the postoperative course was
      uneventful. No complementary treatment was therefore considered. The histological
      examination diagnosis was chondroma. Radiological workup performed at four years
      follow-up did not reveal any recurrence of the lesion. Pathogenic, clinico
      radiological and therapeutic issues are discussed and the literature reviewed.

PMID- 18061631
TI  - [Results of a survey system for neurosurgical site infections, October 1998
      January 2003].
AB  - BACKGROUND AND PURPOSE: In the neurosurgery setting, incidence of surgical site
      infections (SSI) are considered as low to moderately low (1 to 10%). These
      infections are nevertheless a major problem because of the associated morbidity
      and mortality. A SSI survey system has been initiated in our neurosurgical unit.
      We report the incidence of SSI and identified SSI risk factors. METHODS: Data
      collected included demographic and medical information recorded with the
      operating room computer system. Any SSI occurring during the patient's
      postsurgical hospital stay or observed at postoperative visits was notified using
      a standardized questionnaire. SSIs were registered using Centers for Disease
      Control criteria. A multiple logistic regression model was used to determine SSI
      incidence and evaluate risk factors for SSI. Results were reported to the
      neurosurgical team every three months. RESULTS: From October 1998 to January
      2003, 7399 operative procedures were collected. One hundred and twenty-two SSIs
      were notified with a mean incidence per patient of 1.65% (95% CI [1.37-1.95]).
      Among the SSIs 42% were superficial, 58% were deep or organ-space. Risk factors
      significantly associated with SSI were operation site (higher risk with CSF
      shunt), operation modality (higher risk with postponed operation) and operation
      duration greater than 75th percentile. CONCLUSION: SSI are an important problem
      in neurosurgery. This SSI survey gave us fundamental information about SSI and
      risk factors. Complementary studies are now necessary about postponed operative
      procedures. Propositions are made to improve the system.

PMID- 18061632
TI  - [Radiation-induced cavernoma of the central nervous system].
AB  - Central nervous system radiation-induced cavernoma (RIC) is a rare entity. We
      report one case with a review of the literature. This case illustrates the
      following features: mean age of 11.7 years at time of radiation and mean latency
      period of nine years for these RIC, which are often numerous (38%), and located
      in the field of the craniospinal radiation therapy. This nosological entity
      belongs to the spectrum of radiation-induced lesions, and requires a long-term
      MRI follow up in patients who underwent cranial radiation therapy.

PMID- 18061633
TI  - The time course of social-emotional processing in early childhood: ERP responses
      to facial affect and personal familiarity in a Go-Nogo task.
AB  - To date, little is known about the neural underpinnings of social-emotional
      processes in young children. The present study investigated the time course of
      children's ERP responses to facial expression and personal familiarity, and the
      effect of these variables on ERP measures of effortful attention in a Go-Nogo
      task. Dense-array EEG was collected from 48 4-6-year-old children who were
      presented with pictures of their mothers' and strangers' happy and angry faces.
      ERPs were scored following face presentation and following a subsequent cue
      signaling a Go or Nogo response. Responses to face presentation showed early
      perceptual components that were larger following strangers' faces, suggesting
      facilitated rapid processing of personally important faces. A mid-latency
      frontocentral negativity was greatest following angry mothers' faces, indicating
      increased attentional monitoring and/or recognition memory evoked by an angry
      parent. Finally a right-lateralized late positive component was largest following
      angry faces, suggesting extended processing of negatively valenced social stimuli
      in general. Following the Go-Nogo response cue, a right-lateralized mid-latency
      negativity thought to measure effortful attention was larger in Nogo than Go
      trials, and following angry than happy faces, possibly reflecting increased
      effortful control required in those conditions. The present study suggests that
      overlapping but differentiated networks for both rapid and elaborative processing
      of important socio-affective information are established by 4-6 years. Moreover,
      the extended spatial and temporal distribution of components suggests a pattern
      of response to social stimuli in which more rapid processes may index personal
      familiarity, whereas temporally extended processes are sensitive to affective
      valence on both familiar and unfamiliar faces.

PMID- 18061634
TI  - The influence of rTMS over prefrontal and motor areas in a morphological task:
      grammatical vs. semantic effects.
AB  - We investigated the differential role of two frontal regions in the processing of
      grammatical and semantic knowledge. Given the documented specificity of the
      prefrontal cortex for the grammatical class of verbs, and of the primary motor
      cortex for the semantic class of action words, we sought to investigate whether
      the prefrontal cortex is also sensitive to semantic effects, and whether the
      motor cortex is also sensitive to grammatical class effects. We used repetitive
      transcranial magnetic stimulation (rTMS) to suppress the excitability of a
      portion of left prefontal cortex (first experiment) and of the motor area (second
      experiment). In the first experiment we found that rTMS applied to the left
      prefrontal cortex delays the processing of action verbs' retrieval, but is not
      critical for retrieval of state verbs and state nouns. In the second experiment
      we found that rTMS applied to the left motor cortex delays the processing of
      action words, both name and verbs, while it is not critical for the processing of
      state words. These results support the notion that left prefrontal and motor
      cortex are involved in the process of action word retrieval. Left prefrontal
      cortex subserves processing of both grammatical and semantic information, whereas
      motor cortex contributes to the processing of semantic representation of action
      words without any involvement in the representation of grammatical categories.

PMID- 18061635
TI  - Hippocampal lesions in rats differentially affect long- and short-trace eyeblink
      conditioning.
AB  - Extensive previous research has implicated the hippocampus as an important
      structure for the acquisition of trace eyeblink conditioning. Evidence from
      multiple species and various lesioning methods shows that the disruption of
      conditioned responding (CR) may be partially dependent on the relative lengths of
      the conditioned stimulus (CS) period and the trace interval. The present study
      systematically manipulated the length of the CS and the trace interval while
      matching the interstimulus intervals (ISI) in rats with or without ibotenic acid
      hippocampal lesions. The long-trace interval condition had a CS duration of 50 ms
      and a trace interval of 500 ms. The short-trace interval condition had a 500 ms
      CS and a 50 ms trace interval. We found that control animals in the long-trace
      interval condition learned at a slower rate than the control animals in the short
      trace interval condition. Lesioned animals in both the trace conditions showed
      deficits in acquisition. Lesioned animals in the short-trace interval condition
      acquired conditioned responses at a rate almost identical to that of the control
      animals in the long-trace interval condition. CR onset latencies were impaired
      for lesioned animals. Peak latencies were not different, indicating no difference
      in the adaptiveness of the CRs. These results suggest that while the hippocampus
      is important for acquisition of trace eyeblink conditioning, performance also
      depends on the parameters used for the task. In particular, the relative lengths
      of the CS period and the trace interval appear to be important.

PMID- 18061636
TI  - The curative and antioxidative efficiency of doramectin and doramectin+vitamin
      AD3E treatment on Psoroptes cuniculi infestation in rabbits.
AB  - In the present study, the efficiency of the administration of doramectin (DOR)
      and DOR+vitamin AD3E (VIT), and the influence of these agents on oxidative stress
      parameters in rabbits infested by Psoroptes cuniculi (P. cuniculi) were
      investigated. DOR (200 microg/kg) and DOR (200 microg/kg)+VIT AD3E were
      administered to infested rabbits intramuscularly (IM). The administration of DOR
      and DOR+VIT improved the healing of ear lesions on day seven. Increase in the
      plasma malondialdehyde (MDA) level and erythrocyte catalase (CAT) activity, and
      decrease in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)
      activities were determined in infested rabbits. In the rabbits which were
      administered DOR+VIT, plasma MDA levels decreased, and erythrocyte GSH-Px and SOD
      activities increased on day seven. In conclusion, DOR and DOR+VIT combination
      were effective against P. cunuculi infestation. Infestation stimulated oxidative
      stress. VIT treatment resulted in antioxidant activity against oxidative stress
      induced by P. cuniculi infestation.

PMID- 18061638
TI  - Dienogest is a selective progesterone receptor agonist in transactivation
      analysis with potent oral endometrial activity due to its efficient
      pharmacokinetic profile.
AB  - Dienogest was introduced as an oral progestin. Yet its strong oral potency on
      endometrial activity is not clearly explained. To circumvent this situation,
      steroid hormone receptor profiling using transactivation assay and endometrial
      activity test in rabbits were carried out with determination of plasma drug
      concentration. Agonistic/antagonistic activity on human progesterone receptor
      (PR), androgen receptor (AR), glucocorticoid receptor (GR), mineralocorticoid
      receptor (MR), estrogen receptor alpha (ERalpha), or estrogen receptor beta
      (ERbeta) were determined. Dienogest activate PR (EC50=3.4 or 10.5 nmol/l) with
      antagonistic activity on AR (EC50=420.6 or 775.0 nmol/l) but not agonistic nor
      antagonistic action on GR, MR (3000 nmol/l). Dienogest activate neither ERalpha
      nor ERbeta (3000 nmol/l). Progesterone activated PR with antagonistic activity on
      AR and on MR. Dydrogesterone showed a similar profile to progesterone.
      Norethisterone activated PR, AR, and ERalpha. Medroxyprogesterone acetate
      activated PR, AR, and GR. Danazol activated PR and AR. Collectively, dienogest
      has a good specificity to PR compared with the other drugs. By oral treatment,
      dienogest showed the strongest endometrial activity (ED50=0.0042 mg/kg) in
      McPhail test among other progestins (ED50 values for MPA, DYG, NES were 0.074,
      1.9, >0.05 mg/kg, respectively). Dienogest showed higher plasma concentrations
      than those of the other progestins with higher doses. The estimated plasma
      concentration of dienogest at ED50 (3.66 nmol/l) was close to its EC50 value to
      activate PR. Thus, the stronger oral activity of dienogest could be explained
      simply by its in vitro potency on PR and its oral pharmacokinetic profile.

PMID- 18061637
TI  - Development of a composite orthopaedic pain scale in horses.
AB  - This study addresses development and validation of a composite multifactorial
      pain scale (CPS) in an experimental equine model of acute orthopaedic pain.
      Eighteen horses were allocated to control (sedation with/without epidural
      analgesia - mixture of morphine, ropivacaine, detomidine and ketamine) and
      experimental groups: amphotericin-B injection in the tarsocrural joint induced
      pain and analgesia was either i.v. phenylbutazone administered post-induction of
      synovitis, or pre-emptive epidural mixture, or a pre-emptive combination of the
      2. Inter- and intra-observer reproducibility was good (0.8<K<1). The key specific
      and sensitive behavioural indices were response to palpation of the painful area,
      posture, and, of lesser value, pawing on the floor, kicking at abdomen and head
      movement. Of particular interest was the statistical correlation observed between
      the CPS and both non-invasive blood pressure (P<0.0001) and blood cortisol
      (P<0.002). This study established the value of some behavioural and physiological
      criteria in determining equine orthopaedic pain intensity and clearly
      demonstrated that pre-emptive, multimodal analgesia provided better management
      than the two other protocols tested.

PMID- 18061639
TI  - Cultivation and differentiation characteristics of human limbal progenitor cells.
AB  - BACKGROUND: The aim of this study was to investigate whether limbal progenitor
      cells can be cultured, expanded and differentiated in vitro not only to enter
      corneal differentiation but also towards RPE (retinal pigment epithelium)
      characteristics. METHODS: A 3mm broad strip of human corneoscleral limbal tissue
      was digested enzymatically and cells were set into cell culture. Differentiation
      status and characteristics, proliferation and phagocytotic activity were assessed
      by immunocytochemical staining in combination with digital and confocal
      microscopy. RESULTS: Immunocytological analysis revealed expression of Nestin and
      p63 marker suggesting progenitor cell properties. Mitotic activity was
      demonstrated by BrdU (bromodesoxyuridine) uptake. Upon consecutive passages,
      corneal differentiation markers were predominantly expressed. Phagocytotic
      activity was demonstrated via uptake of FITC (fluorescein isothiocyanate)
      labelled latex beads. RPE markers Bestrophin and Cytokeratin 8/18 as well as
      glial marker GFAP and neuronal marker MAP with respective controls were negative
      indicating no differentiation towards characteristics of retinal pigment
      epithelium or neural and glial lineage. CONCLUSIONS: The results suggest that
      isolation and cultivation of proliferating and phagocytotic cells from the human
      corneal limbus was achieved which showed characteristics of both progenitor and
      differentiated corneal cells. No evidence was found for the hypothesis of
      spontaneous differentiation potential towards RPE lineage or neuronal
      characteristics, providing evidence of the inherent directional capacity of
      limbal progenitor cells.

PMID- 18061640
TI  - Painful toxins acting at TRPV1.
AB  - Many plant and animal toxins cause aversive behaviors in animals due to their
      pungent or unpleasant taste or because they cause other unpleasant senstations
      like pain. This article reviews the current state of knowledge of toxins that act
      at the TRPV1 ion channel, which is expressed in primary sensory neurons, is
      activated by multiple painful stimuli and is thought to be a key pain sensor and
      integrator. The recent finding that painful peptide "vanillotoxin" components of
      tarantula toxin activate the TRPV1 ion channel to cause pain led us to survey
      what is known about toxins that act at this receptor. Toxins from plants, spiders
      and jellyfish are considered. Where possible, structural information about sites
      of interaction is considered in relation to toxin-binding sites on the Kv ion
      channel, for which more structural information exists. We discuss a developing
      model where toxin agonists such as resiniferatoxin and vanillotoxins are proposed
      to interact with a region of TRPV1 that is homologous to the "voltage sensor" in
      the Kv1.2 ion channel, to open the channel and activate primary sensory nerves,
      causing pain.

PMID- 18061641
TI  - Neutralization of hemorrhagic snake venom metalloproteinase HR1a from
      Protobothrops flavoviridis by human monoclonal antibody.
AB  - Human monoclonal antibodies (HuMAbs) against HR1a from Protobothrops (formerly
      Trimeresurus) flavoviridis venom were obtained by the fusion of SP2/0-Ag14
      myeloma cells and spleen cells from KM mice immunized with purified HR1a. The
      ability of HuMAbs to neutralize the HR1a was determined by in vitro
      neutralization assay and by neutralization of the hemorrhagic activity. The
      initial screening of over 300 hybridoma fusion wells resulted in the
      establishment of 80 HR1a-reactive hybridomas. Of the reactive clones, HuMAb HR1a
      7 and HR1a-18 neutralized both proteolytic and hemorrhagic activity of HR1a.
      Mapping of epitope recognized by the reactive clones was performed by using an
      ELISA that measured antibody binding to overlapping peptides (15 amino acid
      peptide offset frameshifted by three residues) covering the metalloproteinase
      domain sequence of HR1a. HuMAbs HR1a-7 and HR1a-18 neutralized HR1a by reacting
      with peptides of EQQRYLNNFRFIELV and IVNTLNETYRYL. The three-dimensional
      structure of HR1a based on a homology modeling predicted that these two epitopes
      are surface exposed.

PMID- 18061642
TI  - Ability of fucoidan to prevent muscle necrosis induced by snake venom myotoxins:
      comparison of high- and low-molecular weight fractions.
AB  - Fucoidan, a natural polysaccharide extracted from brown seaweed, inhibits the
      myotoxic phospholipases A(2) present in the venoms of crotalid snakes. This study
      evaluated the influence of molecular weight on the ability of fucoidan to prevent
      muscle necrosis when rapidly administered after injection of a purified myotoxin
      or crude venom of Bothrops asper, in a mouse model. It was hypothesized that
      smaller fucoidan fragments, being of higher diffusibility to tissues, might have
      a better neutralizing efficiency in vivo. Fucoidan was subjected to acid
      hydrolysis to obtain low-molecular weight fragments (F(L)), or to gel filtration
      to isolate its high-molecular weight fraction (F(H)). These two preparations were
      standardized to the same neutralizing potency by preincubation assays, and
      subsequently tested in vivo, by independent administration assays. Local i.m.
      administration of either F(H) or F(L), immediately after i.m. injection of
      myotoxin II, prevented nearly 50% of muscle necrosis, albeit with no difference
      between the two preparations. Muscle necrosis was not reduced when either F(H) or
      F(L) was administered by i.v. route, immediately after i.m. toxin injection. When
      tested against crude venom, which contains several myotoxin isoforms, the
      immediate in situ i.m. injection of F(H) still inhibited myonecrosis by nearly
      one-half of the effect recorded in the untreated group, whereas F(L) was
      ineffective. It is concluded that, in this model, and in contrast to
      expectations, the use of smaller fucoidan fragments to prevent muscle damage
      induced by snake venom myotoxins is not advantageous, when compared with larger
      fucoidan molecules.

PMID- 18061643
TI  - Associations between subjective and objective visual function in patients with
      unilateral macular holes.
AB  - Forty-six patients with uniocular macular holes and unaffected, fellow eyes were
      studied to evaluate inter- and intraocular associations between various objective
      tests of visual function and perceived visual ability. The affected eye had
      significant associations between visual acuity (VA) and the fovea threshold test,
      but for the fellow eye only VA and low-contrast VA 10% were associated. The
      reduction in visual acuity under low-contrast conditions relative to high
      contrast did not differ between the affected eye and the healthy eye. Subjective
      visual ability seems to depend more on the visual acuity of the affected eye than
      the healthy eye.

PMID- 18061644
TI  - Application of layered double hydroxides for removal of oxyanions: a review.
AB  - Layered double hydroxides (LDHs) are lamellar mixed hydroxides containing
      positively charged main layers and undergoing anion exchange chemistry. In recent
      years, many studies have been devoted to investigating the ability of LDHs to
      remove harmful oxyanions such as arsenate, chromate, phosphate, etc. from
      contaminated waters by both surface adsorption and anion exchange of the
      oxyanions for interlayer anions in the LDH structure. This review article
      provides an overview of the LDH synthesis methods, the LDH characterization
      techniques, and the recent advancement that has been achieved in oxyanion removal
      using LDHs, highlighting areas of consensus and currently unresolved issues.
      Experimental studies relating to the sorption behaviors of LDHs with various
      oxyanions, and the kinetic models adopted to explain the adsorption rate of
      oxyanions from aqueous solution onto LDHs, have been comprehensively reviewed.
      This review discusses several key factors such as pH, competitive anions,
      temperature, etc., that influence the oxyanion adsorption on LDHs. The
      reusability of LDHs is discussed and some mechanistic studies of oxyanion
      adsorption on LDHs are highlighted. The sorption capacities of LDHs for various
      oxyanions are also compared with those of other adsorbents. In addition, this
      review critically identifies the shortcomings in current research on LDHs, such
      as the common weaknesses in the adopted methodology, discrepancies among reported
      results and ambiguous conclusions. Possible improvement of LDHs and potential
      areas for future application of LDHs are also proposed.

PMID- 18061645
TI  - Cleavage of RNA by an amphiphilic compound lacking traditional catalytic groups.
AB  - Recently, in experiments with combinatorial libraries of amphiphilic compounds
      lacking groups, known as catalysts of transesterification reaction, we discovered
      novel RNA-cleaving compounds [N. Kovalev, E. Burakova, V. Silnikov, M. Zenkova,
      V. Vlassov, Bioorg. Chem. 34 (2006) 274-286]. In the present study, we
      investigate cleavage of RNA by the most active representative of these libraries,
      compound named Dp12. Sequence-specificity of RNA cleavage and influence of
      reaction conditions on cleavage rate suggested that Dp12 enormously accelerates
      spontaneous RNA cleavage. Light scattering experiments revealed that the RNA
      cleavage proceeds within multiplexes formed by assembles of RNA and Dp12
      molecules, at Dp12 concentration far below critical concentration of micelle
      formation. Under these conditions, Dp12 is presented in the solution as
      individual molecules, but addition of RNA to this solution triggers formation of
      the multiplexes. The obtained data suggest a possible mechanism of RNA cleavage,
      which includes interaction of the compound with RNA sugar-phosphate backbone
      resulting in changing of ribose conformation. This leads to juxtaposition of the
      2'-hydroxyl group and internucleotide phosphorus atom at a distance needed for
      the transesterification to occur.

PMID- 18061647
TI  - The ABC-Pyramid Atmospheric Research Observatory in Himalaya for aerosol, ozone
      and halocarbon measurements.
AB  - In this work we present the new ABC-Pyramid Atmospheric Research Observatory
      (Nepal, 27.95 N, 86.82 E) located in the Himalayas, specifically in the Khumbu
      valley at 5079 m a.s.l. This measurement station has been set-up with the aim of
      investigating natural and human-induced environmental changes at different scales
      (local, regional and global). After an accurate instrumental set-up at ISAC-CNR
      in Bologna (Italy) in autumn 2005, the ABC-Pyramid Observatory for aerosol
      (physical, chemical and optical properties) and trace gas measurements (ozone and
      climate altering halocarbons) was installed in the high Khumbu valley in February
      2006. Since March 2006, continuous measurements of aerosol particles (optical and
      physical properties), ozone (O3) and meteorological parameters as well as weekly
      samplings of particulate matter (for chemical analyses) and grab air samples for
      the determination of 27 halocarbons, have been carried out. These measurements
      provide data on the typical atmospheric composition of the Himalayan area between
      India and China and make investigations of the principal differences and
      similarities between the monsoon and pre-monsoon seasons possible. The study is
      carried out within the framework of the Ev-K2-CNR "SHARE-Asia" (Stations at High
      Altitude for Research on the Environment in Asia) and UNEP-"ABC" (Atmospheric
      Brown Clouds) projects. With the name of "Nepal Climate Observatory-Pyramid" the
      station is now part of the Observatory program of the ABC project.

PMID- 18061646
TI  - Aging-associated truncated form of p53 interacts with wild-type p53 and alters
      p53 stability, localization, and activity.
AB  - Evidence has accumulated that p53, a prototypical tumor suppressor, may also
      influence aspects of organismal aging. We have previously described a p53 mutant
      mouse model, the p53+/m mouse, which is cancer resistant yet exhibits reduced
      longevity and premature aging phenotypes. p53+/m mice express one full length p53
      allele and one truncated p53 allele that is translated into a C-terminal fragment
      of p53 termed the M protein. The augmented cancer resistance and premature aging
      phenotypes in the p53+/m mice are consistent with a hyperactive p53 state. To
      determine how the M protein could increase p53 activity, we examined the M
      protein in various cellular contexts. Here, we show that embryo fibroblasts from
      p53+/m mice exhibit reduced proliferation and cell cycle progression compared to
      embryo fibroblasts from p53+/- mice (with equivalent wild-type p53 dosage). The M
      protein interacts with wild-type p53, increases its stability, and facilitates
      its nuclear localization in the absence of stress. Despite increasing p53
      stability, the M protein does not disrupt p53-Mdm2 interactions and does not
      prevent p53 ubiquitination. These results suggest molecular mechanisms by which
      the M protein could influence the aging and cancer resistance phenotypes in the
      p53+/m mouse.

PMID- 18061649
TI  - Involvement of eosinophils in the onset of asthma.

PMID- 18061648
TI  - Reducing asthma health disparities in poor Puerto Rican children: the
      effectiveness of a culturally tailored family intervention.
AB  - BACKGROUND: Island and mainland Puerto Rican children have the highest rates of
      asthma and asthma morbidity of any ethnic group in the United States. OBJECTIVE:
      We evaluated the effectiveness of a culturally adapted family asthma management
      intervention called CALMA (an acronym of the Spanish for "Take Control, Empower
      Yourself and Achieve Management of Asthma") in reducing asthma morbidity in poor
      Puerto Rican children with asthma. METHODS: Low-income children with persistent
      asthma were selected from a national health plan insurance claims database by
      using a computerized algorithm. After baseline, families were randomly assigned
      to either the intervention or a control group. RESULTS: No significant
      differences between control and intervention group were found for the primary
      outcome of symptom-free days. However, children in the CALMA intervention group
      had 6.5% more symptom-free nights, were 3 times more likely to have their asthma
      under control, and were less likely to visit the emergency department and be
      hospitalized as compared to the control group. Caregivers receiving CALMA were
      significantly less likely to feel helpless, frustrated, or upset because of their
      child's asthma and more likely to feel confident to manage their child's asthma.
      CONCLUSION: A home-based asthma intervention program tailored to the cultural
      needs of low income Puerto Rican families is a promising intervention for
      reducing asthma morbidity.

PMID- 18061650
TI  - Allergy to human seminal fluid: cross-reactivity with dog dander.
AB  - BACKGROUND: Human seminal plasma (HSP) allergy is uncommon, with symptoms ranging
      from vulvovaginal pruritus to life-threatening anaphylaxis. Although several
      seminal plasma allergens have been reported and their molecular masses have been
      estimated to range between 12 and 75 kd, the prostate-specific antigen (PSA) has
      recently been identified as a causative allergen. Given that in a large number of
      cases symptoms appeared during or after the first intercourse, a cross-reactivity
      phenomenon might be implicated. OBJECTIVE: We sought to assess the presence of
      IgE cross-reactivity among proteins from dog epithelium and HSP and to attempt to
      identify the allergens involved. METHODS: Forty-one patients with dog epithelium
      allergy were selected. One of them experienced anaphylaxis in contact with her
      husband's seminal plasma. Skin prick tests, serum specific IgE measurements, SDS
      PAGE immunoblotting, and inhibition tests were performed to study the pattern of
      IgE-binding proteins and the potential cross-reactivity between HSP and dog
      epithelium. Mass spectrometry was carried out to identify the protein involved in
      allergy reactions. RESULTS: Twenty-four percent of the sera from patients with
      dog epithelium allergy recognized an IgE-binding band of 28 kd in HSP
      immunoblotting. Mass spectrometry identified this band as the PSA. SDS-PAGE
      immunoblotting-inhibition showed a complete IgE-binding inhibition when sera from
      these patients were preincubated with dog dander extract. CONCLUSIONS: IgE cross
      reactivity among proteins from dog dander and human PSA is demonstrated.

PMID- 18061651
TI  - How readable are the American Academy of Allergy, Asthma & Immunology "Tips to
      remember" leaflets?

PMID- 18061652
TI  - Nasal nitric oxide as a noninvasive marker in the antibiotic treatment of acute
      bacterial sinusitis.

PMID- 18061653
TI  - Perturbations of natural killer cell regulatory functions in respiratory allergic
      diseases.
AB  - BACKGROUND: Allergic diseases are characterized by abnormal responses to
      allergens favored by an inappropriate regulation of the T(H)1-T(H)2 polarization.
      Natural killer (NK) cells give rise to a complex NK/dendritic cell (DC) cross
      talk that would help T(H)1 responses. OBJECTIVE: By analyzing peripheral blood NK
      cells from 12 patients with either allergic rhinitis or rhinitis and intermittent
      asthma, we evaluated whether these cells were impaired in their ability to
      interact with DCs. METHODS: Different circulating NK cell subsets were analyzed
      by flow cytofluorimetry. Mixed NK/DC cultures were performed to assess the
      reciprocal functional interactions. NK cells were analyzed for their ability to
      induce DC maturation and cytokine production, and to kill immature DCs. In
      addition, DCs were assessed for their ability to induce cytokine production by NK
      cells. RESULTS: We first analyzed the CD56++CD16+/- cells, a subset of
      circulating NK cells that is able to respond to DCs by proliferating and
      producing IFN-gamma. Our analysis revealed that this NK cell subpopulation was
      significantly reduced in most patients. This was reflected by reduced NK cell
      mediated IFN-gamma production in response to DCs. Also, the capability of
      promoting DC maturation and/or killing immature DCs, a function sustained by
      CD56+CD16+ NK cells, was reduced in most patients. CONCLUSIONS: We suggest that
      allergic diseases are accompanied by a partial impairment of the NK cell
      capability of promoting and maintaining appropriate T(H)1 responses.

PMID- 18061654
TI  - Adiponectin and inflammation: consensus and controversy.
AB  - Circulating levels of adiponectin decrease with increasing visceral obesity and
      are lower in patients with type 2 diabetes, the metabolic syndrome, and
      cardiovascular disease compared with controls matched by body mass index. Several
      reports demonstrated anti-inflammatory effects of adiponectin. Because increased
      adipose tissue is associated with low-grade chronic inflammation and
      proinflammatory factors inhibit adiponectin production, the current hypothesis
      states that chronic inflammation associated with visceral obesity inhibits
      production of adiponectin, perpetuating inflammation. The negative correlation
      between adiponectin and markers of inflammation in the aforementioned conditions
      supports this hypothesis. In contrast with disorders typically associated with
      excess adiposity and positive energy balance, adiponectin levels are elevated-
      rather than decreased--in classic chronic inflammatory/autoimmune diseases that
      are unrelated to increased adipose tissue, such as rheumatoid arthritis, SLE,
      inflammatory bowel disease, type 1 diabetes, and cystic fibrosis. In these
      patients, adiponectin levels positively--rather than negatively--correlate with
      inflammatory markers. Furthermore, proinflammatory effects of adiponectin have
      been reported in tissues such as joint synovium and colonic epithelium. Thus,
      adiponectin is regulated in the opposite direction and may exert differential
      functions in classic versus obesity-associated inflammatory conditions. This
      article discusses this apparent paradox and presents possible alternative and/or
      complementary explanations.

PMID- 18061656
TI  - Higher evidence for specific immunotherapy than reported in the ARIA update.

PMID- 18061657
TI  - Cigarette smoking and allergic sensitization: a 32-year population-based cohort
      study.
AB  - BACKGROUND: Cigarette smoke has immunosuppressant effects, but its effect on
      allergic sensitization is unclear. OBJECTIVE: To investigate associations between
      parental and personal smoking and skin prick tests (SPTs) for atopy in a
      population-based birth cohort of 1037 participants followed to adulthood.
      METHODS: Parental history of atopic disease, parental smoking, and personal
      smoking were obtained at multiple assessments between birth and age 32 years.
      Atopy was assessed by SPTs for 11 common inhaled allergens at ages 13 and 32
      years. RESULTS: Children of atopic parents were less likely to have positive SPTs
      at age 13 years if either parent smoked (odds ratio, 0.55; P = .009). This
      association was not significant after adjusting for breast-feeding history,
      number of siblings, and childhood socioeconomic status. Subjects with atopic
      parents were also less likely to develop positive results to SPTs between ages 13
      and 32 years if they smoked themselves (odds ratio, 0.18; P < .001). This
      reduction in risk remained significant after adjusting for multiple potential
      confounding factors. Neither parental nor personal smoking was significantly
      associated with allergic sensitization among subjects whose parents did not have
      a history of atopic disease. Few of those with positive SPT results at age 13
      years had negative tests at age 32 years, and there was no evidence that this was
      influenced by smoking. CONCLUSION: Personal and parental smoking is associated
      with a reduced risk of allergic sensitization in people with a family history of
      atopy.

PMID- 18061658
TI  - Application of novel communication technologies to the study of farm families: a
      randomized controlled trial.
AB  - OBJECTIVE: The objective of this pilot study was to evaluate the efficacy of
      three different communication technologies for collection of health outcomes from
      farm households. METHODS: A randomized controlled trial was conducted in central
      Saskatchewan, Canada in 2006. The 94 farms completing the baseline questionnaire
      were randomly assigned to follow-up by regular mail (n=30), computer telephony
      (n=32), or their choice of regular mail, computer telephony, or e-mail follow-up
      (n=32). The primary endpoints were absolute differences in the proportions of
      farms using the assigned method to provide follow-up data, 2 months post
      recruitment. RESULTS: Of the total study population, 51 (54.3%) provided follow
      up information. Farms in the regular mail arm were more likely to submit follow
      up data than farms in the other arms (27/30 regular mail vs. 23/32 choice vs.
      2/32 computer telephony). The differences in proportions between the computer
      telephony and other study arms were highly significant (e.g., absolute difference
      between regular mail and computer telephony 83.7% [95% CI: 70.1%, 97.3%;
      p<0.001]). CONCLUSION: The optimal method for health outcome data collection from
      farm households in our study is regular mail. Despite their novelty and
      attractiveness, caution is warranted when adopting modern communication
      technologies in population health research.

PMID- 18061659
TI  - Mitochondrial involvement in non-alcoholic steatohepatitis.
AB  - Non-alcoholic steatohepatitis (NASH) is an increasing recognized condition that
      may progress to end-stage liver disease. There are consistent evidences that
      mitochondrial dysfunction plays a central role in NASH whatever its origin.
      Mitochondria are the key controller of fatty acids removal and this is part of an
      intensive gene program that modifies hepatocytes to counteract the excessive fat
      storage. Mitochondrial dysfunction participates at different levels in NASH
      pathogenesis since it impairs fatty liver homeostasis and induces overproduction
      of ROS that in turn trigger lipid peroxidation, cytokines release and cell death.
      In this review we briefly recall the role of mitochondria in fat metabolism and
      energy homeostasis and focus on the role of mitochondrial impairment and
      uncoupling proteins in the pathophysiology of NASH progression. We suggest that
      mitochondrial respiratory chain, UCP2 and redox balance cooperate in a common
      pathway that permits to set down the mitochondrial redox pressure, limits the
      risk of oxidative damage, and allows the maximal rate of fat removal. When the
      environmental conditions change and high energy supply occurs, hepatocytes are
      unable to replace their ATP store and steatosis progress to NASH and cirrhosis.
      The beneficial effects of some drugs on mitochondrial function are also
      discussed.

PMID- 18061660
TI  - Effect of sulfated astragalus polysaccharide on cellular infectivity of
      infectious bursal disease virus.
AB  - Four kinds of astragalus polysaccharides (APSs), APS(t), APS(40), APS(50) and
      APS(60), were extracted by water decoction and one-step or stepwise ethanol
      precipitation methods, and modified by chlorosulfonic acid-pyridine method to
      obtain four sulfated APSs (sAPSs) (sAPS(t), sAPS(40), sAPS(50), sAPS(60)),
      respectively. The effects of four sAPSs on cellular infectivity of bursal disease
      virus (IBDV) were compared by MTT method taking non-modified APS(t) as control.
      The results showed that modified sAPSs inhibited IBDV to infect CEF significantly
      in comparison with non-modified APS(t), which indicated that sulfated
      modification could enhance the antiviral activity of the APS, by which it would
      be expected to develop a new-type antiviral drug.

PMID- 18061661
TI  - Prediction of preeclampsia - a workshop report.
AB  - Understanding the mechanisms of disease responsible for the syndrome of
      preeclampsia as well as early risk assessment is still a major challenge. The
      concentrations of circulating proteins in maternal blood such as placental growth
      factor, soluble vascular endothelial growth factor receptor-1 and soluble
      endoglin are altered weeks before the onset of clinical symptoms of the syndrome.
      Recently, other proteins in maternal serum, such as activin A, inhibin A, PAPP-A,
      and PP13 have been suggested to be of value in first trimester risk assessment.
      Since preeclampsia is a syndrome, it seems unlikely that a single test will
      predict all forms of preeclampsia. This realization has led to the formulation of
      a new conceptual framework suggesting that a combination of markers (biochemical
      and/or biophysical) may be required to conduct comprehensive risk assessment for
      the syndrome.

PMID- 18061663
TI  - Cortistatin-8, a synthetic cortistatin-derived ghrelin receptor ligand, does not
      modify the endocrine responses to acylated ghrelin or hexarelin in humans.
AB  - Cortistatin (CST), a neuropeptide with high structural homology with somatostatin
      (SST), binds all SST receptor (SST-R) subtypes but, unlike SST, also shows high
      binding affinity to ghrelin receptor (GHS-R1a). CST exerts the same endocrine
      activities of SST in humans, suggesting that the activation of the SST-R might
      mask the potential interaction with ghrelin system. CST-8, a synthetic CST
      analogue devoid of any binding affinity to SST-R but capable to bind the GHS-R1a,
      has been reported able to exert antagonistic effects on ghrelin actions either in
      vitro or in vivo in animals. We studied the effects of CST-8 (2.0 microg/kg i.v.
      as a bolus or 2.0 microg/kg/h i.v. as infusion) on both spontaneous and ghrelin-
      or hexarelin- (1.0 microg/kg i.v. as bolus) stimulated GH, PRL, ACTH and cortisol
      secretion in 6 normal volunteers. During saline, no change occurred in GH and PRL
      levels while a spontaneous ACTH and cortisol decrease was observed. As expected,
      both ghrelin and hexarelin stimulated GH, PRL, ACTH and cortisol secretion
      (p<0.05). CST-8, administered either as bolus or as continuous infusion, did not
      modify both spontaneous and ghrelin- or hexarelin-stimulated GH, PRL, ACTH and
      cortisol secretion. In conclusion, CST-8 seems devoid of any modulatory action on
      either spontaneous or ghrelin-stimulated somatotroph, lactotroph and corticotroph
      secretion in humans in vivo. These negative results do not per se exclude that,
      even at these doses, CST-8 might have some neuroendocrine effects after prolonged
      treatment or that, at higher doses, may be able to effectively antagonize ghrelin
      action in humans. However, these data strongly suggest that CST-8 is not a
      promising candidate as GHS-R1a antagonist for human studies to explore the
      functional interaction between ghrelin and cortistatin systems.

PMID- 18061662
TI  - Immuno-proteomic approach to excitation--contraction coupling in skeletal and
      cardiac muscle: molecular insights revealed by the mitsugumins.
AB  - A comprehensive understanding of excitation-contraction (E-C) coupling in
      skeletal and cardiac muscle requires that all the major components of the Ca(2+)
      release machinery be resolved. We utilized a unique immuno-proteomic approach to
      generate a monoclonal antibody library that targets proteins localized to the
      skeletal muscle triad junction, which provides a structural context to allow
      efficient E-C coupling. Screening of this library has identified several
      mitsugumins (MG); proteins that can be localized to the triad junction in
      mammalian skeletal muscle. Many of these proteins, including MG29 and
      junctophilin, are important components in maintaining the structural integrity of
      the triad junction. Other triad proteins, such as calumin, play a more direct
      role in regulation of muscle Ca(2+) homeostasis. We have recently identified a
      family of trimeric intracellular cation-selective (TRIC) channels that allow for
      K(+) movement into the endoplasmic or sarcoplasmic reticulum to counter a portion
      of the transient negative charge produced by Ca(2+) release into the cytosol.
      Further study of TRIC channel function and other novel mitsugumins will increase
      our understanding of E-C coupling and Ca(2+) homoeostasis in muscle physiology
      and pathophysiology.

PMID- 18061664
TI  - Ocular side effects in chronic myeloid leukemia patients treated with imatinib.
AB  - Imatinib mesylate is a selective inhibitor of the bcr/abl, c-kit and PDGF
      receptor tyrosine kinases. Its ocular toxicity is little known with mild
      periorbital oedema being the most commonly reported side effect. We here describe
      our experience on ocular complications in imatinib treated Ph+ CML patients,
      which consisted of a wide spectrum of adverse effects ranging from periobital
      oedema to serious adverse events such as glaucoma.

PMID- 18061665
TI  - Outcome of treatment with Hyper-CVAD regimen in Chinese patients with acute
      lymphocytic leukemia.
AB  - Modern intensive chemotherapy regimens have improved the prognosis for adult
      patients with acute lymphocytic leukemia (ALL). With these regimens, the complete
      response (CR) rates are approximately 75% and long-term disease-free survival
      (DFS) rates are about 20-35%. For patients with high-risk ALL, DFS rates are only
      20% or less. Hyper-CVAD regimen is effective in ALL and aggressive non-Hodgkin
      lymphomas (NHL) with increased CR rates and DFS rates. Between June 2002 and
      October 2006, 53 consecutive adult patients with newly diagnosed adult ALL were
      treated with Hyper-CVAD regimen for six to eight cycles. The alternating courses
      were given every 3-4 weeks or earlier if count recovery occurred. CR rates of
      73.6% were achieved in 39 patients, the estimated 2-year survival rate was 82.9%
      and the estimated 2-year event-free survival (EFS) rate was 87.3%. Side effects
      were as expected, mostly attributed to myelosuppression. Analysis of prognostic
      factors suggested that some previously well-established poor prognostic factors
      such as the degree of leukocytosis and central nervous system (CNS) or testicular
      involvement were less important with this dose-intensive regimen. However,
      patients with mediastinal disease had lower CR rates (P<0.05), with the presence
      of hepatomegaly and t(9;22) abnormalities had poor survival (P<0.05). Compared
      with other established adult ALL regimens, Hyper-CVAD regimen was associated with
      significantly better CR rates, overall survival and EFS rates. The long-term
      follow-up results of Hyper-CVAD were favorable.

PMID- 18061667
TI  - Systemic mastocytosis with plasma cell dyscrasia: report of a case.
AB  - Systemic mastocytosis (SM) comprises a heterogeneous group of disorders
      characterized by infiltration of bone marrow and other tissues by neoplastic mast
      cells. A subset of patients with SM has associated hematologic malignancy usually
      of myeloid origin and comprises an entity termed systemic mastocytosis with
      associated clonal hematological non-mast cell lineage disease (SM-AHNMD) by the
      current WHO classification. Reports of clonal lymphoid malignancies associated
      with SM are rare. We describe a patient who was simultaneously diagnosed with
      indolent SM and a plasma cell dyscrasia fitting the definition of monoclonal
      gammopathy of undetermined significance (MGUS). We also discuss the pathologic
      interaction between the neoplastic mast cells of SM and the lymphoid/plasma cell
      malignancy when these two entities coexist.

PMID- 18061666
TI  - Lack of association of NQO1 and GSTP1 polymorphisms with multiple myeloma risk.
AB  - Individual differences in xenobiotica metabolising capacity can influence
      susceptibility to multiple myeloma. NQO1 and GSTT1 polymorphisms were recently
      reported as risk factors for multiple myeloma and GSTP1 genotype was found to be
      a prognostic marker for therapy outcome in multiple myeloma. The aim of this
      study was to determine whether specific defective alleles of NQO1 (P187S) and
      GSTP1 (I105V) genes are associated with increased risk of multiple myeloma.
      Individual genotypes of 128 patients affected by multiple myeloma and 245 healthy
      controls were determined and our results do not support any major role of NQO1 or
      GSTP1 polymorphisms in multiple myeloma pathogenesis.

PMID- 18061668
TI  - Variation of success of Leptopilina boulardi in Drosophila yakuba: the mechanisms
      explored.
AB  - Despite an increasing knowledge of insect immune defences and virulence
      strategies used by parasitoids to escape them, the mechanisms underlying
      variation of success between parasitoid strains are still poorly understood. We
      have investigated this point using two lines of the parasitoid wasp Leptopilina
      boulardi that differ in virulence towards Drosophila yakuba. By injecting oil
      drops in D. yakuba larvae parasitized by virulent IS(y) females and then
      dissecting the larvae at different times following injection, we demonstrate that
      the IS(y) line alters host encapsulation ability but only during the early
      parasitism period. This effect is mimicked by injecting venom gland extracts,
      indicating that venom proteins are likely involved in immunosuppression. By
      contrast, the IS(m) line, unsuccessful on D. yakuba, has no immunosuppressive
      effect. This variation in virulence may be explained by the striking difference
      we report in haemocytic profiles between IS(m)- and IS(y)-parasitized larvae. We
      discuss our results in the light of our knowledge of the strategies evolved by
      Leptopilina species to counteract the D. melanogaster immune system as well as
      the role of parasitoid venoms in intra-specific variation of parasitoid
      virulence.

PMID- 18061669
TI  - Essential elements in the coding region of mRNA for translation of ColE2 Rep
      protein.
AB  - Translation initiation of mRNA encoding the plasmid-specified initiator protein
      (Rep) required for initiation of the ColE2 plasmid DNA replication is fairly
      efficient in Escherichia coli despite the absence of a canonical Shine-Dalgarno
      sequence. Although a GA cluster sequence exists upstream the initiation codon,
      its activity as the SD sequence has been shown to be very inefficient. Deletion
      analyses have shown that there are sequences important for the Rep translation in
      the regions upstream the GA cluster sequence and downstream the initiation codon.
      To further define regions important for translation of the Rep mRNA, a set of the
      ColE2 rep genes bearing single-base substitution mutations in the coding region
      near the initiation codon was generated and their translation activities
      examined. We showed that translation of the Rep mRNA was reduced by some of these
      mutations in a region ranging at least 70 nucleotides from the initiation codon
      in the coding region, indicating the presence of translation enhancer(s) outside
      the translation initiation region which is covered by the ribosome bound to the
      initiation codon. Some of them seem to be essential and specific for translation
      of the ColE2 Rep mRNA due to the absence of a canonical SD sequence.

PMID- 18061670
TI  - Effects of temperature and oxygen concentration in sediment toxicity testing.
AB  - Joint effects of temperature and oxygen concentrations for the results of
      sediment toxicity tests were studied at 10 and 20 degrees C with 40% and 80%
      dissolved oxygen (DO) saturation. Growth, feeding rate, and reproduction of
      Lumbriculus variegatus (Oligochaete) and growth, emergence, and survival of
      Chironomus riparius (Diptera) were tested in a polluted and in a reference
      sediment. Both the feeding of L. variegatus and the emergence of C. riparius were
      significantly retarded at low temperature. Additionally, differences in the sex
      ratio of the emerged adults of C. riparius were observed. The oxygen
      concentration alone did not have any significant effect on the endpoints, but
      significant combined effects of polluted sediment and low DO were observed on the
      biomass of L. variegatus. The standard sediment toxicity tests might offer only
      limited data for risk assessment of contaminated sediments at sites where the
      actual conditions largely differ from the laboratory conditions.

PMID- 18061671
TI  - Effects of supplemental ultraviolet-B and cadmium on growth, antioxidants and
      yield of Pisum sativum L.
AB  - The impact of supplemental UV-B irradiation (sUV-B) and cadmium (Cd, 68 micromol
      kg(-1) soil) singly and in combination was studied on growth, pigments, enzymatic
      and non-enzymatic antioxidants, lipid peroxidation (LPO), uptake and
      translocation of Cd and yield of pea plants under field condition. Compared to
      the control, both the stresses individually and in combination led to in
      reductions in growth, photosynthetic pigments, ascorbic acid, catalase (CAT)
      activity and yield, whereas a reverse trend was observed for flavonoids, thiols
      and proline contents, superoxide dismutase (SOD) and peroxidase (POD) activities,
      and LPO. The uptake and translocation of Cd increased in different plant parts
      with duration of its treatment and also when applied with sUV-B. Combined
      treatment of sUV-B and Cd inhibited the growth and various metabolic processes
      antagonistically except the CAT activity which showed additive response. Further,
      CAT activity may be used as a bioindicator parameter to evaluate the individual
      and interactive effects of both the stresses.

PMID- 18061672
TI  - Influence of exposure scenario on pesticide toxicity in the midge Kiefferulus
      calligaster (Kieffer).
AB  - In aquatic environments, many factors determine the overall impact of a toxic
      event, constituting "exposure scenarios" that must be understood so that risk
      assessment strategies can be successfully applied. In this work, an experimental
      design was planned to investigate the influence of the organism age, duration of
      exposure and subsequent recovery period (after cessation of toxic exposure) on
      chlorpyrifos or carbendazim toxicity to Kiefferulus calligaster. The endpoints
      studied were cholinesterase (ChE) activity and glutathione S-transferase (GST)
      activity. The influence of age and exposure time and the existence of recovery
      depend on the chemical and the biomarkers tested, suggesting that no general rule
      can be applied when trying to assess overall toxicity of pesticides and that
      detailed knowledge has to be acquired on a case-to-case basis.

PMID- 18061673
TI  - Trans-generation study of the effects of nonylphenol ethoxylate on the
      reproduction of the snail Biomphalaria tenagophila.
AB  - Nonylphenols ethoxylates (NPEs) are surfactants used in a variety of products.
      They are found in domestic sewage, industrial effluents and as contaminants in
      water bodies. This study was undertaken to evaluate the effects of NPE with 9.5
      ethoxylate units (NPE9.5; 0, 0.01, 0.1, 1.0 mg/L) on the reproduction of the
      snail Biomphalaria tenagophila. Adult snails (F0 generation) were exposed to NPE
      for 8 weeks. The F1 generation continued to be exposed from embryo to
      reproductive maturity while their descendants (F2) were exposed until day 10
      after spawning. We determined the effects of NPE9.5 on the fecundity (8-week
      production of eggs and egg masses) of mature F0 and F1 snails. Developmental
      toxicity was investigated in F1 and F2 embryos. The two highest concentrations of
      NPE9.5 reduced the fecundity of F0. In the F1 generation, the lowest
      concentration enhanced the number of eggs laid per snail while the intermediate
      concentration had no effect and the highest one decreased the fecundity thereby
      suggesting a biphasic effect of NPE9.5. Study-derived NOECs (no-observed-effect
      concentrations) for NPE were: fecundity, F0=10 microg/L, F1<10 microg/L;
      developmental toxicity, F1=100 microg/L, F2<10 microg/L. Results, therefore,
      indicated that B. tenagophila is highly vulnerable to NPE and that trans
      generation exposure to NPE9.5 aggravates its reproductive toxicity.

PMID- 18061674
TI  - Lipid rafts regulate ethanol-induced activation of TLR4 signaling in murine
      macrophages.
AB  - Toll-like receptors (TLRs) response is critical in innate resistance to
      infection. Alcohol consumption has been shown to suppress the inflammatory
      response mediated through TLR4, down regulating the production of inflammatory
      cytokines. We recently reported that low concentrations of ethanol activate TLR4
      signaling in astrocytes and triggers neuroinflammation. Because macrophages are
      important cells in innate immunity, we investigate whether low concentrations of
      ethanol could stimulate the TLR4 signaling response in murine RAW 264.7
      macrophages, and the mechanism involved in the ethanol-induced TLR4 activation.
      Our results show that while ethanol, at high concentrations (100mM) or in the
      presence of the LPS, suppresses the TLR4 response, low to moderate levels (10
      50mM) activate the TLR4 response and triggers the stimulation of the mitogen
      activated protein kinases (MAPKs) and the transcription factor NF-kappaB
      pathways, leading to the production of nitric oxide (NO) and inflammatory
      cytokines. Pre-treatment with anti-TLR4 Abs abolishes the effects of ethanol on
      the production of cytokines. We also present evidence that stimulation with
      either ethanol or LPS induces translocation and clustering of TLR4 and signaling
      molecules (IRAK and MAPKs) into lipid rafts. Treatment with either streptolysin-O
      or saponin, lipid rafts disrupting agents, abolishes the ethanol-induced
      activation of the TLR4/IL-1RI signaling pathway. In summary, the present results
      demonstrate that low to moderate concentrations of ethanol are capable of
      stimulating TLR4/IL-1RI response, and provide evidence of a novel mechanism by
      which ethanol, through its interaction with membrane rafts, can promote TLR4/IL
      1RI recruitment and signaling.

PMID- 18061675
TI  - S. aureus IgG-binding proteins SpA and Sbi: host specificity and mechanisms of
      immune complex formation.
AB  - The evasion of the host immune response is central to the pathogenicity of
      Staphylococcus aureus, and is facilitated by the ability of the cell wall
      associated protein A (SpA) to bind immunoglobulin G Fc fragments, thereby
      impeding phacocytosis and classical pathway complement fixation. SpA also acts as
      a B-cell superantigen through interactions with the heavy-chain variable part of
      Fab fragments, and sequesters immunoglobulins by forming large insoluble immune
      complexes with human IgG. Here we show that the formation of insoluble immune
      complexes is mediated by the binding of (VH3+) Fab fragments in addition to Fc,
      and that SpA forms soluble complexes with IgG Fc fragments. We compared these
      results with those for Sbi, a second staphylococcal immunoglobulin-binding
      protein, and note that this protein requires only the Fc fragment for
      precipitation with human IgG. Homology models of immunoglobulin-binding domains
      of SpA and Sbi in complex with Fc reveal the molecular basis of the Fab
      independent formation of insoluble complexes by Sbi. Finally, we compared the
      sequences of the spa and sbi genes from human strains to those infecting a range
      of animal hosts to determine whether Sbi and SpA have acquired specificity for
      host IgG. We note remarkable sequence conservation within the IgG-binding domains
      of these genes, consistent with a lack of host specificity. The Fab-independent
      binding of IgG by Sbi could have significant clinical implications. The use of
      SpA in immunoadsorption therapy can cause severe side-effects, thought to be
      mediated by Fc gamma R recognition and complement fixation. The formation of
      insoluble immune complexes with Sbi occurs only via Fc binding and free Fc
      regions are unlikely to be available for Fc gamma R recognition and complement
      fixation.

PMID- 18061677
TI  - The carbohydrate recognition domain of Langerin reveals high structural
      similarity with the one of DC-SIGN but an additional, calcium-independent sugar
      binding site.
AB  - Langerin is a type II transmembrane oligosaccharide receptor on Langerhans cells
      (LCs), a prominent subclass of dendritic cells (DCs) that mediate immune
      responses in epithelia and play a role in HIV degradation. Its extracellular
      moiety comprises a neck region with several heptad repeats and an exposed carboxy
      terminal calcium-type carbohydrate-recognition domain (CRD). The CRD of human
      Langerin, which was expressed as a soluble protein in the periplasm of E. coli,
      was crystallized both alone and in the presence of two sugars, followed by X-ray
      analyses to resolutions of 2.5A for apo-Langerin and to 1.6A and 2.1A for the
      complexes with mannose and maltose, respectively. The fold of the Langerin CRD
      (dubbed LangA) resembles that of other typical C-type lectins such as DC-SIGN.
      However, especially in the long loop region (LLR), which is responsible for
      carbohydrate-binding, two additional secondary structure elements are present: a
      3(10) helix and a small beta-sheet arising from the extended beta-strand 2, which
      enters into a hairpin and a new strand beta2'. Unexpectedly, the crystal
      structures in the presence of maltose and mannose reveal two sugar-binding sites.
      One is calcium-dependent and structurally conserved in the C-type lectin family
      whereas the second one represents a novel, calcium-independent type. Based on
      these data, a model for the binding of mannan, a component of many endogenous as
      well as viral glycoproteins, is proposed and the differences in binding behavior
      between Langerin and DC-SIGN with respect to the Lewis X carbohydrate antigen and
      its derivatives can be explained. Therefore, the crystal structure of LangA
      should be helpful for the development of new marker reagents selective for LCs
      and also of therapeutic compounds that may enhance the inhibitory role of
      Langerin towards HIV infection.

PMID- 18061676
TI  - MicroRNA targets in immune genes and the Dicer/Argonaute and ARE machinery
      components.
AB  - We studied 613 genes which regulate immunity and, utilizing predictive
      algorithms, identified 285 genes as microRNA (miRNA or miR) targets. Of these,
      approximately 250 are newly predicted gene-miR interactions. The frequency of
      predicted miRNA binding sites in immune gene 3'UTRs indicated preferential
      targeting of immune genes compared to the genome. Major targets include
      transcription factors, cofactors and chromatin modifiers whereas upstream
      factors, such as ligands and receptors (cytokines, chemokines and TLRs), were, in
      general, non-targets. About 10% of the immune genes were 'hubs' with eight or
      more different miRNAs predicted to target their 3'UTRs. Hubs were focused on
      certain key immune genes, such as BCL6, SMAD7, BLIMP1, NFAT5, EP300 and others.
      NF-kappaB and p53 do not themselves have binding sites for miRNAs but rather
      these pathways are targeted by miRNAs at downstream sites. MHC class II genes
      lacked miRNA targets but binding sites were identified in the CIITA gene and were
      shown experimentally to repress IFN-gamma-induced MHC class II activation.
      Unexpectedly, factors involved in regulating message stability via AU-rich
      elements (ARE) were heavily targeted. Moreover, multiple components involved in
      the generation and effector functions of miRNAs (Dicer and Argonautes) were
      themselves miRNA targets suggesting that a subset of miRNAs may indirectly
      control their own production as well as other miRNAs.

PMID- 18061678
TI  - Neonatal exposure to decabrominated diphenyl ether (PBDE 209) results in changes
      in BDNF, CaMKII and GAP-43, biochemical substrates of neuronal survival, growth,
      and synaptogenesis.
AB  - Mammals have a marked period of rapid brain growth and development (BGS), which
      is postnatal in mice and rats, spanning the first 3-4 weeks of life and reaching
      its peak around postnatal day 10. CaMKII, GAP-43 and BDNF play important roles
      during the BGS in mammals. One class of flame retardants, polybrominated diphenyl
      ethers (PBDEs), are present and increasing in the environment and in human milk,
      which is also true for the only congener still in use, decabrominated diphenyl
      ether (PBDE 209). In the present study, the brains from 1, 3, 7, 10, 14 and 28
      days old mice, were analysed for CaMKII and GAP-43. The level of CaMKII increases
      continuously during the neonatal period, while GAP-43 has a bell-shaped ontogeny
      curve, which peaks around postnatal day 10, in mouse brain. Furthermore, the
      effects of PBDE 209 on the developmental expression of CaMKII, GAP-43 and BDNF
      were examined in mice. Neonatal NMRI-male mice were orally exposed on days 3
      20.1mgPBDE 209/kg body weight. The animals were euthanized 7 days after exposure
      to PBDE 209 and levels of CaMKII, GAP-43 and BDNF were analysed in different
      brain regions. The protein analysis showed that CaMKII increased significantly in
      hippocampus, but not in cortex, in animals 7 days after exposure to PBDE 209. GAP
      43 showed a significant increase in hippocampus and a significant decrease in
      cortex of animals 7 days after exposure to PBDE 209. BDNF decreased significantly
      in hippocampus, but not in cortex, in mice 7 days after exposure to PBDE 209.
      This shows that PBDE 209 affects important proteins involved in normal maturation
      of the brain and further strengthen our findings concerning PBDE 209 as a
      developmental neurotoxicological agent.

PMID- 18061679
TI  - Electron paramagnetic resonance study of peripheral blood mononuclear cells from
      patients with refractory solid tumors treated with Triapine.
AB  - The metal chelator Triapine, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone,
      is a potent inhibitor of ribonucleotide reductase. EPR spectra consistent with
      signals from Fe-transferrin, heme, and low-spin iron or cupric ion were observed
      in peripheral blood mononuclear cells (PBMCs) obtained from patients treated with
      Triapine. One signal that is unequivocally identified is the signal for Fe
      transferrin. It is hypothesized that Fe uptake is blocked by reactive oxygen
      species generated by FeT(2) or CuT that damage transferrin or transferrin
      receptor. A potential source for the increase in the heme signal is cytochrome c
      released from the mitochondria. These results provide valuable insight into the
      in vivo mechanism of action of Triapine.

PMID- 18061680
TI  - New insights into the chemical structure and composition of the pentavalent
      antimonial drugs, meglumine antimonate and sodium stibogluconate.
AB  - The chemical structures of the pentavalent antimonial drugs, meglumine antimonate
      (MA) and sodium stibogluconate (SSG), were re-evaluated using electrospray
      ionization mass spectrometry (ESI-MS) and osmolarity measurements. Both MA and
      SSG were found to contain 1:1, 1:2, 2:2 and 2:3 Sb(V)-ligand complexes. ESI-MS
      analysis of MA showed negatively-charged 1:1 (m/z 364) and 2:2 (m/z 765) Sb(V)
      meglumine complexes, supporting the predominance of zwitterionic species in
      solution. Our data are consistent with a structure for the 1:2 Sb(V)-meglumine,
      which differs from that previously postulated, with two positively-charged amino
      groups and one negatively-charged antimonate group. Instead of the commonly
      hypothesized structure for SSG, in which two Sb atoms are linked by an oxygen, an
      alternative structure is proposed, based on the ability of Sb(V)-gluconate
      complexes to polymerize. MA (or SSG) in concentrated aqueous solutions, such as
      of MA (or SSG) in its commercial form, is expected to consist mainly of a mixture
      of 2:2, 2:3 and 2:1 Sb(V)-ligand complexes, as suggested by the 2:1 Sb-to
      particle ratio found by osmometry. 1:1 Sb(V)-ligand complexes in MA and SSG are
      expected to play an important pharmacological role, as suggested by the slow
      increase of osmolarity of MA solution upon dilution at 37 degrees C (half-time of
      20min).

PMID- 18061681
TI  - Infants' visual and auditory communication when a partner is or is not visually
      attending.
AB  - In the current study we investigated infants' communication in the visual and
      auditory modalities as a function of the recipient's visual attention. We
      elicited pointing at interesting events from thirty-two 12-month olds and thirty
      two 18-month olds in two conditions: when the recipient either was or was not
      visually attending to them before and during the point. The main result was that
      infants initiated more pointing when the recipient's visual attention was on them
      than when it was not. In addition, when the recipient did not respond by sharing
      interest in the designated event, infants initiated more repairs (repeated
      pointing) than when she did, again, especially when the recipient was visually
      attending to them. Interestingly, accompanying vocalizations were used
      intentionally and increased in both experimental conditions when the recipient
      did not share attention and interest. However, there was little evidence that
      infants used their vocalizations to direct attention to their gestures when the
      recipient was not attending to them.

PMID- 18061682
TI  - Organization of cell and tissue circadian pacemakers: a comparison among species.
AB  - In most animal species, a circadian timing system has evolved as a strategy to
      cope with 24-hour rhythms in the environment. Circadian pacemakers are essential
      elements of the timing system and have been identified in anatomically discrete
      locations in animals ranging from insects to mammals. Rhythm generation occurs in
      single pacemaker neurons and is based on the interacting negative and positive
      molecular feedback loops. Rhythmicity in behavior and physiology is regulated by
      neuronal networks in which synchronization or coupling is required to produce
      coherent output signals. Coupling occurs among individual clock cells within an
      oscillating tissue, among functionally distinct subregions within the pacemaker,
      and between central pacemakers and the periphery. Recent evidence indicates that
      peripheral tissues can influence central pacemakers and contain autonomous
      circadian oscillators that contribute to the regulation of overt rhythmicity. The
      data discussed in this review describe coupling and synchronization mechanisms at
      the cell and tissue levels. By comparing the pacemaker systems of several
      multicellular animal species (Drosophila, cockroaches, crickets, snails,
      zebrafish and mammals), we will explore general organizational principles by
      which the circadian system regulates a 24-hour rhythmicity.

PMID- 18061683
TI  - Assessing transient cross-frequency coupling in EEG data.
AB  - Synchronization of oscillatory EEG signals across different frequency bands is
      receiving waxing interest in cognitive neuroscience and neurophysiology, and
      cross-frequency coupling is being increasingly linked to cognitive and perceptual
      processes. Several methods exist to examine cross-frequency coupling, although
      each has its limitations, typically by being flexible only over time or over
      frequency. Here, a method for assessing transient cross-frequency coupling is
      presented, which allows one to test for the presence of multiple, dynamic, and
      flexible cross-frequency coupling structure over both time and frequency. The
      method is applied to intracranial EEG data, and strong coupling between gamma (
      approximately 40-80 Hz) and upper theta ( approximately 7-9 Hz) was observed.
      This method might have useful applications in uncovering the electrophysiological
      correlates of cognitive processes.

PMID- 18061685
TI  - Referential delusions of communication and interpretations of gestures.
AB  - Gestures are an important aspect of non-verbal communication, but people with
      schizophrenia have poor comprehension of them. However, the tests of gesture
      comprehension that have been used present only scenes in which interpersonal
      meaning is communicated, though there is evidence that people with psychotic
      disorders tend to perceive communications where none were intended. Such mistakes
      about non-verbal behaviour are the hallmark of a subtype of delusions of
      reference identified as delusions of communication. Thus we hypothesised that
      patients with delusions of communication would tend to misinterpret incidental
      movements as gestures and, since delusions are often derogatory to the self, they
      would also tend to misinterpret gestures as insulting. Patients with acute
      psychotic symptoms (n=64) were recruited according to a 2 x 2 design (presence
      vs. absence of delusions of communication by presence vs. absence of auditory
      hallucinations). They, and 57 healthy controls, were presented with 20 brief
      video clips in which an actor either made a well-known gesture or an incidental
      movement. After each clip, they selected one of four interpretations: a correct
      interpretation if a gesture had been presented; the interpretation of a different
      gesture; an insulting interpretation; no gesture intended (correct for incidental
      movements). The patients made significantly more errors of all kinds than the
      controls, perceived significantly more of the incidental movements as gestures,
      and selected significantly more insulting interpretations of the clips. These
      differences between patients and controls were almost wholly due to patients with
      delusions of communication. These results suggest that the difficulties that
      people with delusions of communication experience in understanding gestures can
      be explained, at least in part, by the misattribution of self-generated internal
      events to external sources.

PMID- 18061684
TI  - The role of tapasin in MHC class I protein trafficking in embryos and T cells.
AB  - Preimplantation mouse embryos express both classical (class Ia) and nonclassical
      (class Ib) MHC class I proteins, and yet are not rejected by the maternal immune
      system. Although the function of the embryonic MHC class Ia proteins is unknown,
      one MHC class Ib protein, Qa-2, the product of the preimplantation embryo
      development (Ped) gene, actually enhances reproductive success. Similar in
      structure to MHC class Ia proteins, Qa-2 protein is a trimer of the alpha (heavy)
      chain, beta(2) microglobulin and a bound peptide. Studies on the folding,
      assembly and trafficking of MHC class Ia molecules to the cell surface have
      revealed this process to be dependent on multiple protein chaperone molecules,
      but information on the role of chaperone molecules in Qa-2 expression is
      incomplete. Here, we report the detection of mRNA for four chaperone molecules
      (TAP1, TAP2, calnexin and tapasin) in preimplantation embryos. We then focused on
      the role of the MHC-dedicated chaperone, tapasin, on Qa-2 protein expression.
      First, we demonstrated that tapasin protein is expressed by preimplantation
      embryos. Then, we used tapasin knockout mice to evaluate the role of tapasin in
      Qa-2 protein expression on both T cells and preimplantation embryos. We report
      here that optimal cell surface expression of Qa-2 is dependent on tapasin in both
      T cells and preimplantation embryos. Identification of the molecules involved in
      regulation of MHC class I protein expression in early embryos is an important
      first step in gaining insight into mechanisms of escape of embryos from
      destruction by the maternal immune system.

PMID- 18061686
TI  - Enhanced green fluorescent protein-expressing human mesenchymal stem cells retain
      neural marker expression.
AB  - Mesenchymal stem cells (MSCs) have the potential to play a role in autologous
      treatment of central nervous system injury or disease. Here we transduced human
      MSCs with enhanced green fluorescent protein (EGFP). We compared the capacity of
      control and EGFP-positive cells to proliferate under normal culture conditions,
      as well as express neural markers following trans-differentiation. EGFP-positive
      cells proliferated comparably to controls, retained EGFP expression over the
      course of multiple passages, and retained neural marker expression at levels
      comparable to control MSCs. Further neurogenic capacity of EGFP-positive human
      MSCs was examined by growth as neural stem cell-like neurospheres. No significant
      difference was observed in the ability of control or EGFP-positive cells to
      generate primary neurospheres or to expand during passage. When examined by
      immunostaining for the presence of neuroectodermal markers, neurosphere-derived
      cells similarly expressed neural markers. We show that human MSCs expressing EGFP
      represent an attractive and practical source of stem cells for the study of
      repair and regeneration in neurological models.

PMID- 18061687
TI  - Wounding prior to challenge substantially improves infectivity of cottontail
      rabbit papillomavirus and allows for standardization of infection.
AB  - The cottontail rabbit papillomavirus (CRPV)/rabbit model has proved useful for
      the investigation of prophylactic and therapeutic vaccines and for the study of
      the pathogenesis of papillomavirus infection. It is currently the only animal
      model in which the entire viral program can be recapitulated, including
      progression to cancer. CRPV DNA is infectious in domestic rabbits and therefore
      mutants can be studied without the need to generate corresponding viruses.
      Although the CRPV animal model is used widely in various laboratories, no
      optimized or standardized method is used for creating CRPV viral and especially
      DNA infections. These different methods have made it difficult for investigators
      to compare results from laboratory to laboratory. A simple and highly efficient
      method is reported here; it has been refined based on previous methodology for
      the production of CRPV infections from both virus and plasmid DNA. This method
      can be adapted easily by other investigators in the field. The resulting
      standardization will aid in the evaluation of data from different laboratories.

PMID- 18061688
TI  - Treatment of yellow fever.
AB  - Yellow fever (YF) is a life-threatening mosquito-borne flaviviral hemorrhagic
      fever (VHF) characterized by severe hepatitis, renal failure, hemorrhage, and
      rapid terminal events with shock and multi-organ failure. A live, attenuated
      vaccine (YF 17D), in wide use for over 60 years, causes a disease identical to
      wild-type virus at an incidence of 2.5x10(-6). Our current understanding of the
      pathogenesis and treatment of YF (described in this brief review) is derived from
      studies of animal models (macaques, hamsters) that reproduce the features of
      human YF and from descriptive studies of human cases of naturally acquired and
      vaccine-associated VHF. The least understood, but potentially most important
      terminal events appear to be due to 'cytokine storm' and represent a potential
      target for therapeutic interventions. Areas for future study include dissection
      of cytokine-mediated events in animal models, the pathogenic role of the profound
      neutrophilia that occurs pre-terminally, the (pathological) role of adaptive
      immune clearance in pathogenesis, and treatments directed at cytokine storm.
      Antibody, interferon-alpha, polyICLC and other immune modulators are highly
      effective when administered before or within a narrow time window after
      infection, but are ineffective when given after the infection is established. A
      few antivirals have been evaluated (ribavirin, tiazofurin, carboxamide,
      pyrazoline compounds). Ribavirin has been used successfully to treat hamsters
      when the drug is given at high doses up to 2 days after virus infection (shortly
      before liver infection), but has not shown promise in nonhuman primate models.
      Future work should focus on evaluating higher doses of ribavirin alone or in
      combinations with potentially synergistic drugs, including interferons. Also
      specific inhibitors against other flaviviruses such as dengue virus should be
      investigated for potential pan-flavivirus activity since recent studies have
      shown that specific targets such as the flavivirus proteases and helicases are
      very similar in structure.

PMID- 18061689
TI  - Improved therapy and outcome for patients with acute myocardial infarction--data
      of the Berlin Myocardial Infarction Registry from 1999 to 2004.
AB  - BACKGROUND: Guidelines for treatment of patients with myocardial infarction (MI)
      have been regularly updated. In addition, a new definition for acute MI has been
      recently established. The aim of our study was to evaluate development of
      treatment and effects on patient outcome. METHODS: We prospectively collected
      data from MI patients who were treated in 22 hospitals in Berlin, Germany, during
      the years 1999 to 2004. In the study we consecutively included 6080 MI patients
      presenting with (STEMI, n=4314) and without persistent ST-segment elevation
      (NSTEMI, n=1766). RESULTS: STEMI and NSTEMI patients showed an increase over time
      in arterial hypertension, smoking, hypercholesterolaemia, history of congestive
      heart failure, and renal failure. The application of acute percutaneous coronary
      intervention increased from 15.3% to 62.3% (p<0.001) for NSTEMI and from 24.7% to
      71.8% (p<0.001) for STEMI patients. Concomitant therapy with beta-blockers, ACE
      inhibitors, statins, GP IIb/IIIa, and aspirin increased in parallel in both
      groups. The decrease in hospital mortality was more pronounced for NSTEMI (13.5%
      vs. 4.6%, p<0.001) than with STEMI patients (13.0% vs. 9.4%, p=0.005).
      CONCLUSIONS: Adherence to guidelines has led to a higher level of hospital care
      for NSTEMI and STEMI patients. Hospital mortality decreased for both groups, with
      a greater impact on NSTEMI patients.

PMID- 18061690
TI  - Prevalence of significant QTc prolongation and long QT syndrome in adolescents
      with syncope.
AB  - A total of 664 high school students having >or=1 episode of syncope and 560
      students without syncope (controls) underwent 12-lead ECG. A significant QT
      prolongation was defined as corrected QT (QTc)>470 ms in male and >480 ms in
      female. A diagnosis of LQTS was made by Schwartz's score. Most students had only
      1 episode of syncope (66.1%), 2 (16.9%), 3 (11.6%), and >or=4 (5.4%). Most
      syncopal episodes were related to non-exertional events with only 11.4% related
      to exertion. The QTc distribution of the study group was almost identical to
      controls with mean QTc of 405.1+/-23.2 vs 402.5+/-23.4 ms, respectively. Only one
      male (0.15%) in the study group had significant QTc prolongation. None met the
      criteria for diagnosis of LQTS (score>or=4). In conclusion, the prevalence of
      LQTS in adolescents having syncope seems to be low in this cohort study.

PMID- 18061691
TI  - Results of a two-year quality control program for a helical tomotherapy unit.
AB  - BACKGROUND AND PURPOSE: Image-guided helical tomotherapy (HT) is a new modality
      for delivering intensity modulated radiation therapy (IMRT) with helical
      irradiation: the slip ring continuously rotates while the couch moves into the
      bore. The radiation source (Linac, 6 MV) is collimated into a fan beam and
      modulated by means of a binary multileaf collimator (MLC). A xenon detector
      array, opposite the radiation source, allows a megavoltage-CT (MVCT) acquisition
      of patient images for set-up verification. The aim of this paper is to report the
      results of a two-year quality control (QC) program for the physical and
      dosimetric characterization of an HT unit installed at our Institute and
      clinically activated in November 2004, in order to monitor and verify the
      stability and the reliability of this promising radiation treatment unit.
      MATERIALS AND METHODS: Conventional Linac acceptance protocols (ATP) and QC
      protocols were adapted to HT with the addition of specific items reflecting
      important differences between the two irradiation modalities. QC tests can be
      summarized as: (a) mechanical and geometrical characterization of the system's
      components: evaluation of alignment among radiation source-gantry rotation plan
      jaws-MLC-MVCT; (b) treatment beam configuration in static condition: depth dose
      curves (PDD) and profiles, output factors, output reproducibility and linearity;
      (c) dynamic component characterization: accuracy and reproducibility of MLC
      positioning; rotational output reproducibility and linearity, leaf latency, couch
      movement constancy; (d) gantry-couch and MLC-gantry synchronization; and (e) MVCT
      image quality. Peculiar periodicity specific tolerance and action levels were
      defined. Ionization chambers (Exradin A1SL 0.056 cc), films (XOmat-V/EDR2), water
      and solid water phantoms were used to perform quality assurance measurements.
      RESULTS: Over a two-year period the final average output variation after possible
      beam output adjustment was -0.2+/-1% for the static condition and equal to 0+/-1%
      for the rotational condition: around 98% of the collected output data was within
      the action level compared to 94% if no beam output adjustment was considered. An
      average energy variation of -0.4+/-0.4% was found. The daily absolute dose
      verification of IMRT plans showed a dose reproducibility of -0.5+/-1.2% and 
      0.4+/-2.2%, for low and high dose gradient regions, respectively. Source-jaws-MLC
      and MVCT alignment results and jaw and leaf positioning accuracy were +/-1mm.
      Couch-gantry-MLC synchrony tests showed good stability level (<or= +/-2mm).
      CONCLUSIONS: QC results indicated good reproducibility of all HT mechanical
      dosimetric performance.

PMID- 18061692
TI  - 3D in vivo dose verification of entire hypo-fractionated IMRT treatments using an
      EPID and cone-beam CT.
AB  - As radiotherapy becomes more complicated, dose and geometry verification become
      more necessary. The aim of this study was to use back-projected EPID-based 3D in
      vivo dosimetry and cone-beam CT (CBCT) to obtain a complete account of the entire
      treatment for a select patient group. Nine hypo-fractionated rectum IMRT patient
      plans were investigated. The absolute dose was reconstructed at multiple planes
      using patient contours and EPID images acquired for all fields during treatment.
      The meso-rectal fat (m-R) was re-delineated on daily CBCT scans, acquired prior
      to each fraction. The total accumulated dose was determined by mapping the m-R
      surface of each fraction to the planned m-R surface. Average planned and measured
      isocentre dose ratios were 0.98 (+/-0.01SD). 3D gamma analysis (3% maximum dose
      and 3mm) revealed mean gamma, gamma(mean)=0.35 (+/-0.03 SD), maximum 1% of gamma
      points, gamma(max1%)=1.02 (+/-0.14SD) and the percentage of points with gamma <
      or = 1, P(gamma < or = 1)=99% (range [96%, 100%]), averaged over all patients.
      CBCT m-R volumes varied by up to 20% of planned volumes, but remained in the high
      dose region. Over-dosage of up to 4.5% in one fraction was measured in the
      presence of gas pockets. By combining EPID dosimetry with CBCT geometry
      information, the total dose can be verified in 3D in vivo and compared with the
      planned dose distribution. This method can provide a safety net for advanced
      treatments involving dose escalation, as well as a full account of the delivered
      dose to specific volumes, allowing adaptation of the treatment from the original
      plan if necessary.

PMID- 18061693
TI  - The significance of a uniform definition of pathological lymph nodes in Hodgkin
      lymphoma: impact of different thresholds for positive lymph nodes in CT imaging
      on staging and therapy.
AB  - BACKGROUND AND PURPOSE: The most commonly used approach for the assessment for
      differentiating malignant versus reactive lymph nodes is the measurement of the
      cross-section diameter of the lymph nodes in the transversal CT-planes. The
      intention of this article is to assess the impact of varying definitions of
      pathological lymph node size in CT-imaging in patients with Hodgkin lymphoma and
      to evaluate its effect on staging, chemotherapy regimes and radiation field size.
      MATERIALS AND METHODS: Pretherapeutic CT-scans of 10 consecutive patients with
      Hodgkin lymphoma have been evaluated based on two different definitions for
      malignant lymph node size; the classification of the German study group for
      Hodgkin lymphoma (1.0 cm) and the classification according to the results of the
      Cotswold consensus meeting 1989 (1.5 cm). RESULTS: Applying the definitions of
      the DHSG and the Cotswold meeting we found more affected lymph node regions
      compared to the evaluation of the referring institutions in 9/10 and 6/10
      patients, higher stages in 2/10 and 1/10 patients, more intense chemotherapy
      regimes in 3/10 and 1/10 and larger radiation fields in 10/10 and 6/10 patients,
      respectively. CONCLUSIONS: Varying definitions of pathologic lymph node size and
      inconsequent application of definitions reduce the comparability between
      different studies and within each study.

PMID- 18061694
TI  - Phantom scatter factors for small MV photon fields.
AB  - BACKGROUND AND PURPOSE: A table of small field (<4 cm width) S(p) values was
      created from measured S(cp) and S(c) data and compared with other authors' work.
      METHODS AND MATERIALS: S(cp) and S(c) values measured with three types of diode
      and a diamond were used to calculate S(p). RESULTS: The results from measurements
      with different detectors were examined to determine the reasons for the
      differences and these were found to be due to detector and phantom-specific
      problems in the experimental determination of S(cp) and S(c). Small field S(p)
      were shown to be independent of beam defining system and linac design and
      dependent only on measurement depth and beam area irradiated. S(p) values
      obtained from S(cp) and S(c) measurements with a photon diode were found to be
      unreliable, due to problems with S(cp) measurements. CONCLUSION: Although the
      electron and stereotactic diodes and the diamond are suitable detectors for S(cp)
      and S(c) measurements, the differences between S(p) values calculated from
      diamond measurements and those calculated from measurements with unshielded
      diodes still require clarification through Monte Carlo modelling. A final table
      of S(p) was produced, for fields >0.5 cm width.

PMID- 18061695
TI  - Monte Carlo simulation of a realistic anatomical phantom described by triangle
      meshes: application to prostate brachytherapy imaging.
AB  - PURPOSE: Monte Carlo codes can simulate the transport of radiation within matter
      with high accuracy and can be used to study medical applications of ionising
      radiations. The aim of our work was to develop a Monte Carlo code capable of
      generating projection images of the human body. In order to obtain clinically
      realistic images a detailed anthropomorphic phantom was prepared. These two
      simulation tools are intended to study the multiple applications of imaging in
      radiotherapy, from image guided treatments to portal imaging. METHODS: We adapted
      the general-purpose code PENELOPE 2006 to simulate a radiation source, an ideal
      digital detector, and a realistic model of the patient anatomy. The
      anthropomorphic phantom was developed using computer-aided design tools, and is
      based on the NCAT phantom. The surface of each organ is modelled using a closed
      triangle mesh, and the full phantom contains 330 organs and more than 5 million
      triangles. A novel object-oriented geometry package, which includes an octree
      structure to sort the triangles, has been developed to use this complex geometry
      with PENELOPE. RESULTS: As an example of the capabilities of the new code,
      projection images of the human pelvis region were simulated. Radioactive seeds
      were included inside the phantom's prostate. Therefore, the resulting simulated
      images resemble what would be obtained in a clinical procedure to assess the
      positioning of the seeds in a prostate brachytherapy treatment. CONCLUSIONS: The
      new code can produce projection images of the human body that are comparable to
      those obtained by a real imaging system (within the limitations of the anatomical
      phantom and the detector model). The simulated images can be used to study and
      optimise an imaging task (i.e., maximise the object detectability, minimise the
      delivered dose, find the optimum beam energy, etc.). Since PENELOPE can simulate
      radiation from 50 eV to 1 GeV, the code can also be used to simulate radiotherapy
      treatments and portal imaging. Using the octree data structure, the new geometry
      model does not significantly increase the computing time when compared to the
      simulation of a much simpler quadric geometry. In conclusion, we have shown that
      it is feasible to use PENELOPE and a complex triangle mesh geometry to simulate
      real medical physics applications.

PMID- 18061696
TI  - Evidence for recombination between PCV2a and PCV2b in the field.
AB  - Genomic sequence analysis demonstrates that porcine circovirus type 2 (PCV2)
      isolates are divided into distinct genotypes. Historically, swine herds in the
      U.S. have been infected with the PCV2a genotype. In 2005, PCV2b was identified in
      North America and with it increased reports of porcine circovirus disease (PCVD).
      A differential PCR technique incorporating PCV2 genotype-specific primers was
      used in the clinical diagnosis of PCVD. A set of 97 diagnostic submissions showed
      that both PCV2a and PCV2b were present in 25% of clinical samples. The
      construction of phylogenetic trees using whole genome sequences from diagnostic
      submissions showed that one isolate, 0737A, was only loosely associated with
      other PCV2b isolates. Analysis of the variable sites between representative PCV2a
      and PCV2b DNA sequences and the 0737A sequence, showed that 0737A was a mosaic
      sequence, with the ORF1 region from PCV2a and ORF2 from PCV2b. This study
      demonstrates that pigs can be naturally infected with multiple PCV2 genotypes and
      that PCV2a/PCV2b recombination events occur in the field.

PMID- 18061697
TI  - Family planning and access to safe and legal abortion are vital to safeguard the
      environment.

PMID- 18061698
TI  - Oral contraceptives and benign breast disease: an update of findings in a large
      cohort study.
AB  - BACKGROUND: This report is an update of findings, first reported in 1981, on the
      relationship between oral contraceptives (OCs) and benign breast disease with
      special reference to OCs containing <50 mcg estrogen. STUDY DESIGN: The Oxford
      Family Planning Association study includes 17,032 women using different methods
      of contraception recruited at 17 family planning clinics between 1968 and 1974.
      These women were subsequently followed up until mid-1994. Among other items,
      information about contraceptive method changes and morbidity as measured by
      hospital referrals was collected during follow-up. RESULTS: The findings in the
      present analysis were broadly similar to those reported in 1981, but based on
      much larger numbers of cases [fibroadenoma (FA), 185 cases; chronic cystic
      disease (CCD), 1361 cases; breast lump with no specific diagnosis (BL), 650
      cases]. Hospital referral rates for FA and CCD (but not BL) declined with
      increasing duration of OC use, with the effect being strongest among recent
      users. The apparent protective effect was present for women using OCs containing
      >50 mcg, 50 mcg and <50 mcg estrogen but not for progestogen-only OCs.
      CONCLUSION: Low-dose combined OCs containing <50 mcg estrogen appear to reduce
      the risk of hospitalization for FA and CCD as well as older preparations
      containing higher doses of estrogen.

PMID- 18061700
TI  - An initial pharmacokinetic study with a Metered Dose Transdermal Systemfor
      delivery of the progestogen Nestorone as a possible future contraceptive.
AB  - BACKGROUND: Transdermal delivery of steroids is gaining popularity for
      contraception and hormone replacement therapy. This study aimed to test metered
      spray delivery of a precise dosage of Nestorone (NES) progestogen as a possible
      transdermal progestogen-only contraceptive. STUDY DESIGN: Six healthy
      postmenopausal volunteers, not recently using any hormonal therapies, comprise
      the sample for this study. Each subject was studied on two occasions with
      multiple blood sampling for assay of NES over a 24-h period: on the first
      occasion, after a single dosage of 3 x 90 microL NES sprays using a specially
      devised, precisely metered delivery device; on the second occasion, following the
      fifth in a series of five daily transdermal dosages of 3 x 90 microL of NES
      spray. Conventional pharmacokinetic parameters were calculated. NES was assayed
      in serum using a specific radioimmunoassay. RESULTS: Mean serum levels of NES
      peaked at around 20 h following dosing, and levels plateaued at 285-290 pmol/L
      after 4-5 days of daily spray application. All subjects achieved satisfactory
      serum levels, although substantial intersubject variation was noted. The apparent
      elimination half-life of NES after the last dose on Day 5 was 26.8 h. No
      unexpected adverse events were encountered. CONCLUSION: This early
      pharmacokinetic trial of a new transdermal steroid delivery system has
      demonstrated the feasibility of achieving serum levels of NES sufficient to block
      ovulation and potentially provide effective contraception.

PMID- 18061699
TI  - Bone status after cessation of use of injectable progestin contraceptives.
AB  - BACKGROUND: Women using injectable progestin contraceptives (IPCs) have lower
      bone mineral density than nonusers. We assessed whether bone loss is completely
      reversible after cessation of IPC use, whether different IPCs have different
      effects and whether effects vary by age at first use. STUDY DESIGN: In a cross
      sectional study in Cape Town, South Africa, 3487 premenopausal black and mixed
      race women aged 18-44 years were interviewed for information on contraceptive
      history and risk factors for decreased bone mineral density, and ultrasound
      measurements of the left calcaneus were taken. Adjusted means of the ultrasound
      measures for categories of IPC use were obtained using multivariable linear
      regression. RESULTS: Current users of IPCs had the lowest ultrasound measures,
      while the measures of women who had ceased IPC use at least 2-3 years previously
      were similar to or greater than those of never users of IPCs. The effects of
      depot medroxyprogesterone acetate and norethisterone enanthate were similar. The
      calcaneus measures were unrelated to age at which use began after control for
      confounding factors. CONCLUSION: The data suggest that bone loss during IPC use
      is reversible and that this loss of bone is completely recovered several years
      after cessation of use.

PMID- 18061701
TI  - Vaginal yeast adherence to the combined contraceptive vaginal ring (CCVR).
AB  - BACKGROUND: The purpose of this study was to evaluate the in vitro adherence of
      different yeasts, isolated from vaginal exudates of patients with vulvovaginal
      candidiasis (VVC), to the combined contraceptive vaginal ring--NuvaRing. STUDY
      DESIGN: Four isolates of Candida sp. and one isolate of Saccharomyces cerevisiae
      were used. Adherence assays were carried out through colony-forming units per
      milliliter (CFU/mL), radiolabeled quantification and scanning electron microscopy
      (SEM) of the ring, and the cell surface hydrophobicity (CSH) of the yeasts was
      determined. RESULTS: All the yeasts were capable of adhering to the vaginal ring,
      as determined by CFU/mL and in the radiolabeled assay. CSH was compatible with
      the adherence by CFU/mL. CONCLUSION: SEM proved the adhesion, which was different
      between Candida albicans and C. tropicalis. The adherence of the tested yeasts to
      the ring could potentially facilitate the development of VVC and recurrent VVC in
      susceptible patients using this contraceptive method.

PMID- 18061702
TI  - The contraceptive vaginal ring: female adolescents' knowledge, attitudes and
      plans for use.
AB  - BACKGROUND: This study aimed to determine female adolescents' knowledge about the
      contraceptive vaginal ring and to assess their attitudes toward and consideration
      of ring use. STUDY DESIGN: We recruited 164 participants, ages 14-21, who
      completed a 62-item, 15-min interview assessing tampon and vaginal product use
      history, reproductive health history and ring awareness. Among those who had
      heard of the ring, knowledge was assessed with a 15-item pretest. All
      participants received a 2-min description of the ring with a demonstration, after
      which attitudes, consideration of use and posttest knowledge were assessed.
      RESULTS: Our study population is unique in that 92% had been sexually active and
      22% who had been sexually active had also been pregnant. The mean age of
      coitarche was 15.2 years, and 35% had ever used emergency contraception. More
      than half (52%) had never heard of the ring. Of those who had heard of it, only
      35% had sufficient knowledge. After a brief demonstration with a vaginal model,
      98.2% acquired sufficient knowledge to use the ring correctly. More than half
      (57.9%) liked the idea of the ring, and 45.7% said that they would consider using
      it. Logistic regression demonstrated that liking the idea of the ring and
      considering its use were associated with comfort using at least one vaginal
      product, with those who were comfortable using a vaginal product being 3.1 times
      more likely to like the idea of the ring compared to those who were not
      comfortable using a vaginal product. Logistic regression also showed that liking
      the idea of the ring was associated with having had at least one pelvic exam.
      CONCLUSIONS: Most participants had limited or no prior ring knowledge. Once
      briefly educated, all had sufficient knowledge and a substantial percentage would
      consider using it. The ring appeals to adolescents and should be routinely
      offered as a method of contraception. Comfort using at least one vaginal product
      is associated with liking the idea of the ring and considering its use.

PMID- 18061703
TI  - Elective pregnancy termination in a large cohort of women with hyperemesis
      gravidarum.
AB  - BACKGROUND: This study was conducted to describe characteristics of women who
      terminated their pregnancies secondary to hyperemesis gravidarum (HG). STUDY
      DESIGN: Data were obtained from a survey provided on an HG Web site from 2003 to
      2005. RESULTS: Of 808 women who completed the survey, 123 (15.2%) had at least
      one termination due to HG, and 49 (6.1%) had multiple terminations. Prominent
      reasons given for the terminations were inability to care for the family and self
      (66.7%), fear that they or their baby could die (51.2%), or that the baby would
      be abnormal (22.0%). These same women were three times as likely to state that
      their health care providers were uncaring or did not understand how sick they
      were [64/123 (52.0%) vs. 168/685 (24.5%), odds ratio 3.34 (95% CI 2.21-5.05),
      p<.001]. CONCLUSION: These data suggest that the physical and psychological
      burden of HG has been underestimated, and that further education within the
      medical community may be warranted.

PMID- 18061704
TI  - Termination of early pregnancy using flexible, low-dose mifepristone-misoprostol
      regimens.
AB  - BACKGROUND: Various regimens of mifepristone and misoprostol are used in medical
      abortion. We examined the effect of a change in protocol from a fixed
      mifepristone-misoprostol interval to a flexible one on the efficacy and uptake of
      medical abortion. In addition, risk factors of incomplete abortions were
      evaluated. STUDY DESIGN: Altogether, 1289 medical abortions were carried out
      between August 2000 and December 2002. Between August 2000 and August 2001, a
      fixed protocol of 200 mg of oral mifepristone followed by 0.4 mg of vaginally
      administered misoprostol 2 days later was used. From September 2001, a flexible
      dosing interval of 1, 2 or 3 days between mifepristone and misoprostol was
      adopted. At the same time, the upper limit of gestational age was increased from
      56 to 63 days. RESULTS: The uptake of medical abortion increased during the study
      period and was 45.8% during the use of fixed protocol versus 54.6% during
      flexible protocol (p<.0001). The rates of complete abortion were 94.9% and 94.4%
      (n.s.), respectively. Continuing pregnancy was rare (0.7%). Among all subjects, a
      history of abortion was associated with a significantly lower rate of complete
      abortion (90.9 vs. 96.3%, p<.002). The other parameters analyzed (age, parity,
      duration of pregnancy, smoking, mifepristone-misoprostol interval) did not have a
      significant effect on the rate of complete abortion. CONCLUSIONS: A flexible
      dosing protocol of mifepristone and misoprostol is effective; thus, its use is
      encouraged. Previous abortion is a significant risk factor of incomplete medical
      abortion. Thus, special attention should be paid to the follow-up of these women.

PMID- 18061705
TI  - A randomized comparison of misoprostol to intrauterine instillation of hypertonic
      saline plus a prostaglandin F2alpha analogue for second-trimester induction
      termination in Uzbekistan.
AB  - BACKGROUND: The study was conducted to compare the efficacy and acceptability of
      second-trimester induction termination using vaginal misoprostol to hypertonic
      saline and d-cloprostenol, a prostaglandin F(2alpha) (PGF) analogue, in Tashkent,
      Uzbekistan. STUDY DESIGN: Eleven clinics providing second-trimester induction
      terminations were randomized to provide one of two regimens for second-trimester
      induction termination: vaginal misoprostol 400 mcg every 3 h or hypertonic 10%
      saline intrauterine instillation plus an intravenous PGF analogue, d
      cloprostenol, 2.5 mg/h. Demographic information, and obstetric and medical
      history data were collected, and interviewers administered questionnaires to
      measure procedural pain and satisfaction. Differences in procedure time and
      complication rate, the primary outcomes, were analyzed with survival analysis and
      chi(2) tests. RESULTS: Of 228 participants, 120 received misoprostol and 108
      received hypertonic saline and d-cloprostenol; the groups did not significantly
      differ by age, parity or gestational age. Both misoprostol and saline procedures
      were effective, with 99.2% and 100% successful abortion rates, respectively.
      Median procedure time (13.1 vs. 29.2 h, p<.001), and number of women with
      retained placenta (2 vs. 70, p<.001) or hemorrhage (3 vs. 19, p=.001) were lower
      for the misoprostol group. Both provider (p<.001) and patient (p<.001) procedural
      satisfaction scores were higher for the misoprostol group. CONCLUSION: While
      equally effective, vaginal misoprostol had a shorter time to abortion, was more
      acceptable to providers and patients and had fewer complications than saline
      instillation plus intravenous administration of a PGF analogue in Tashkent. This
      evidence supports change of the existing standard of care for second-trimester
      induction termination in Uzbekistan.

PMID- 18061706
TI  - Effect of octapeptide: FSH binding inhibitor on cyclicity of bonnet monkeys
      (Macaca radiata).
AB  - BACKGROUND: The gonadotropins follicle-stimulating hormone (FSH) and luteinizing
      hormone play an important role in the development of ovarian follicles, and a
      number of autocrine/paracrine factors secreted by the ovary are known to directly
      or indirectly regulate gonadotropin action. The objective of the present study
      was to elucidate the effect of octapeptide (OP) on cyclicity and hormonal profile
      of bonnet monkeys, the menstruating Old World primates. STUDY DESIGN: Our group
      has purified one such factor from human ovarian follicular fluid, which inhibits
      the binding of FSH to the granulosa cells. N-terminal eight-amino-acid sequence
      of this peptide has been deduced, which is referred to as the OP. It has shown an
      antifertility effect in marmosets, the New World primates. In the present study,
      the bonnet monkeys were divided into two groups, namely, the treated group (n=5),
      which was administered with OP (250 mcg/kg body weight/day) intramuscularly
      during the follicular phase, and the control group (n=6), which was injected with
      vehicle (saline). Blood was collected every other day, and progesterone levels
      were estimated by enzyme-linked immunosorbent assay. RESULTS: Animals in the
      control group demonstrated normal plasma progesterone levels and exhibited normal
      cyclicity. On the other hand, in the treated group, progesterone levels decreased
      by 65.8%, as compared with that in pretreatment cycles. This probably disturbed
      the cyclicity, thus causing amenorrhea (73.0+/-6.7 days).

PMID- 18061707
TI  - Suppression of fertility in male albino rats following the administration of 50%
      ethanolic extract of Aegle marmelos.
AB  - BACKGROUND: Plants have served as a natural source of antifertility substances.
      The reactivated interest in the evaluation of some lead plants for fertility
      prompted us to undertake studies on the antifertility potential of Aegle marmelos
      leaves. STUDY DESIGN: Fifty percent ethanolic extract from the leaves of A.
      marmelos (AMLEt) was prepared. The effect of A. marmelos leaf extract on the
      reproductive system of male albino rats was investigated at three different
      doses, namely, 100, 200 and 300 mg(-1) kg (-1) day(-1) for each rat for 60 days.
      Recovery was also investigated after a withdrawal of 120 days. RESULTS: All the
      major accessory sex organs shed weight postadministration of the extract. There
      was a marked reduction in motility and density of the sperm derived from cauda
      epididymis of the treated animals. A. marmelos reduced fertility of male rats by
      100% at the 300-mg dose level. Serum testosterone levels also decreased
      significantly in all the experimental groups. The protein, glycogen and lipid
      peroxidation content of the testes was significantly reduced at the highest dose
      level; a highly significant increase in testicular cholesterol was observed along
      with a highly significant reduction in the sialic acid contents of testes,
      epididymis and seminal vesicles. Blood tests did not point to distress in any of
      the vital organs. Withdrawal of the extract restored all the altered parameters
      including organ weights, fertility, testosterone levels and tissue biochemistry
      to control levels after 120 days. CONCLUSIONS: Taken together, it is inferred
      that the leaf extract of A. marmelos (AMLEt) suppresses fertility in male rats.
      Complete recovery of fertility was observed following the withdrawal of drug.
      Absence of any deleterious effect on the vital organs points to the safe use of
      the extract.

PMID- 18061708
TI  - Effect of Mimosa pudica root extract on vaginal estrous and serum hormones for
      screening of antifertility activity in albino mice.
AB  - BACKGROUND: Several plants are traditionally used as birth control agents by the
      rural people in India. Mimosa pudica is one of the folk medicinal plants commonly
      used as antifertility agent in some places in India. The present work was carried
      out to evaluate the claimed antifertility effect of the plant by carrying out
      pharmacological studies with the root extract of the plant. STUDY DESIGN: Air
      dried roots of M. pudica were extracted using methanol. Dried methanol extract of
      the root was administered orally to Swiss albino mice for 21 consecutive days.
      Estrous cycle, reproductive hormones (LH, FSH, prolactin, estradiol and
      progesterone) and number of litters produced were studied in both control and
      extract-administered groups by using standard methods. Phytochemical studies of
      the methanolic root extract were carried out using qualitative and thin-layer
      chromatography methods. RESULTS: M. pudica root extract, when administered orally
      at a dose of 300 mg/kg body weight/day, prolonged the length of the estrous cycle
      with significant increase in the duration of the diestrous phase and reduced the
      number of litters in albino mice. The number of litters was increased in the
      posttreatment period. The analysis of the principal hormones (LH, FSH, prolactin,
      estradiol and progesterone) involved in the regulation of the estrous cycle
      showed that the root extract altered gonadotropin release and estradiol
      secretion. CONCLUSIONS: The root extract of M. pudica has antifertility effect as
      it prolongs the estrous cycle and disturbs the secretion of gonadotropin hormones
      in albino mice. The decrease in FSH level in the proestrus and estrus stages in
      the extract-administered group compared with those of control animals indicates
      the disturbance of estrous cycle and ovulation through suppression of FSH.

PMID- 18061709
TI  - Cervical preparation for second-trimester surgical abortion prior to 20 weeks of
      gestation.
AB  - Roughly 11% of induced abortions in the United States are performed after 14
      weeks of gestation, most commonly by dilation and evacuation (D&E). For a D&E
      procedure, the cervix must be dilated sufficiently to allow passage of operative
      instruments and products of conception without injuring the uterus or cervical
      canal. Preoperative preparation of the cervix reduces the risk of cervical
      laceration and uterine perforation. The cervix may be prepared with osmotic
      dilators, prostaglandin analogues, or both. Osmotic dilators currently available
      in the United States include Dilapan-S, Lamicel, and laminaria. Laminaria tents
      are made from dehydrated seaweed and require 12-24 h to achieve greatest
      dilation. The synthetic products, Dilapan-S and Lamicel, achieve maximum effect
      within 6 h. Dilapan-S achieves greater dilation than the others and, thus,
      requires fewer dilators to be placed but may be more difficult to remove. For
      same day procedures, Dilapan-S and Lamicel are preferable to laminaria. A single
      set of one to several dilators is usually adequate for D&E before 20 weeks of
      gestation. Additional sets over 1-2 days may be needed in challenging cases.
      Misoprostol, a prostaglandin analogue, is sometimes used instead of osmotic
      dilators; however, the data to support such use are limited. Misoprostol is
      inferior to overnight dilation with laminaria for cervical priming prior to D&E.
      Misoprostol use as an adjunct to overnight osmotic dilation is only marginally
      beneficial for priming beyond 16 weeks and does not truly demonstrate any benefit
      before 19 weeks of gestation. Limited data demonstrate the safety of misoprostol
      prior to D&E in patients with a uterine scar. The Society of Family Planning
      recommends preoperative cervical preparation to decrease the risk of
      complications when performing a D&E prior to 20 weeks of gestation. The three
      currently available osmotic dilators (laminaria, Lamicel, and Dilapan-S) are safe
      and effective for this use. Since no single protocol has been found to be
      superior, clinical judgment is warranted when selecting a method of preoperative
      cervical preparation.

PMID- 18061710
TI  - Drainage of peripancreatic-fluid collections: is EUS really necessary?

PMID- 18061711
TI  - Drainage of pancreatic fluid collections: is EUS really necessary?

PMID- 18061712
TI  - Efficacy of diclofenac in the prevention of post-ERCP pancreatitis in
      predominantly high-risk patients: a randomized double-blind prospective trial.
AB  - BACKGROUND: Pancreatitis is one of the major complications of ERCP and endoscopic
      sphincterotomy. It has been shown that nonsteriodal anti-inflammatory drugs are
      potent inhibitors of phospholipase A(2), activity which is increased in
      pancreatitis. A previous study showed reduction of post-ERCP pancreatitis with
      administration of rectal diclofenac. OBJECTIVE: The aim of this study was to
      determine whether prophylactic oral diclofenac will reduce the incidence and the
      severity of ERCP-induced pancreatitis, especially in high-risk patients. DESIGN:
      Single-center, randomized, double-blinded, prospective study. SETTING: Indiana
      University Medical Center. PATIENTS: A total of 207 evaluable patients were
      randomized to receive either diclofenac 50 mg or placebo by mouth 30 to 90
      minutes before and 4 to 6 hours after ERCP. RESULTS: The groups were similar with
      regard to patient demographics and to patient and procedure risk factors for post
      ERCP pancreatitis. The overall incidence of post-ERCP pancreatitis was 16.4%. It
      occurred in 17 of 102 patients in the control group (16.7%) and in 17 of 105
      patients in diclofenac group (16.2%). The pancreatitis was graded mild in 9.8%,
      moderate in 5.9%, and severe 1.0% of the control group, and mild in 10.5%,
      moderate in 4.8%, and severe in 1.0% of the diclofenac group. In high-risk
      patients, the incidence of post-ERCP pancreatitis was 17.3%. It occurred in 18.0%
      (16/89) in the control group and in 17.8% (16/90) in the diclofenac group. There
      was no significant difference between the groups in the frequency or severity of
      post-ERCP pancreatitis in overall and high-risk patients; however, the power of
      the study was less than 45%. CONCLUSIONS: Prophylactic orally administered
      diclofenac was not observed to affect the frequency or severity of post-ERCP
      pancreatitis in high-risk patients.

PMID- 18061713
TI  - Pancreatitis associated with double-balloon enteroscopy: how common is it?

PMID- 18061715
TI  - Autoimmune pancreatitis: time for a collective effort.

PMID- 18061714
TI  - Clinical factors predictive of spontaneous remission or relapse in cases of
      autoimmune pancreatitis.
AB  - BACKGROUND: The rates of spontaneous remission and relapse of autoimmune
      pancreatitis (AIP) are not known. OBJECTIVE: To study the clinicopathologic
      factors predictive of remission and relapse in cases of AIP. DESIGN:
      Retrospective study. PATIENTS: Of the 20 patients with AIP, complete response to
      steroid therapy was recognized in 12 patients, and the remaining 8 patients
      improved without steroid therapy. Seven patients experienced a relapse. RESULTS:
      Patients who were seronegative for immunoglobulin (Ig) G4, had no obstructive
      jaundice, no diabetes mellitus, no swelling of the duodenal papilla, negative
      staining of the duodenal papilla for IgG4, and focal pancreatic swelling showed a
      greater tendency toward spontaneous remission (P < .05). The results of
      multivariate analysis revealed that negative staining of the duodenal papilla for
      IgG4 was the only independent predictor of spontaneous remission of AIP (odds
      ratio [OR] 1.395, P = .0304). Seropositivity for IgG4, diffuse swelling of the
      pancreas, and the presence of stricture in the lower part of the bile duct were
      significantly associated with a relapse of AIP (P < .05) according to the results
      of univariate analysis, whereas the results of multivariate analysis revealed
      only diffuse pancreatic swelling as an independent predictor of a relapse of AIP
      (OR 26.197, P = .0331). CONCLUSIONS: Endoscopic findings are of useful prognostic
      value, because patients with AIP and with negative staining of the duodenal
      papilla for IgG4 appeared to have a higher frequency of remission without steroid
      therapy. Patients with AIP and with diffuse pancreatic swelling were found to be
      at an increased risk of relapse after the initial steroid administration.

PMID- 18061716
TI  - Distal common bile duct angulation and common bile duct stones: who cares?

PMID- 18061717
TI  - Cool runnings in a previously hot topic: has wireless video capsule endoscopy
      come of age?

PMID- 18061718
TI  - Evaluation of capsule endoscopy in active, mild-to-moderate, overt, obscure GI
      bleeding.
AB  - BACKGROUND: The role of capsule endoscopy (CE) in the diagnosis of active mild-to
      moderate GI bleeding (GIB) immediately after a negative EGD and ileocolonoscopy
      has not been prospectively evaluated. OBJECTIVE: To estimate the diagnostic yield
      and clinical significance of CE in patients with acute, obscure, overt, mild-to
      moderate GIB. DESIGN: A single-center prospective study. PATIENTS: During a 3
      year period, 573 patients admitted to the hospital with acute mild-to-moderate
      GIB were included in this study. Among them, 37 patients (6.5%) with negative
      endoscopic findings, after urgent upper- and lower-GI endoscopies, underwent CE
      within the first 48 hours to identify the source of bleeding. RESULTS: CE
      revealed active bleeding in 34 patients and a diagnostic yield of 91.9%,
      including angiodysplasias in 18 patients, ulcers in 3 patients, and tumors in 2
      patients. In the remaining 11 patients (32%), CE revealed the site of bleeding:
      distal duodenum in 1 case (9%), jejunum in 6 cases (54%), ileum in 2 cases (18%),
      and cecum in 2 cases (18%). From the 37 bleeders, 16 were managed conservatively,
      14 endoscopically, and 7 surgically. During a 12-month follow-up period, bleeding
      recurrence was observed in 5 of 32 (15.6%). LIMITATIONS: This study had a limited
      number of patients. CONCLUSIONS: CE appeared to have a high diagnostic yield in
      patients with acute, mild-to-moderate, active hemorrhage of obscure origin when
      performed in the hospital after a negative standard endoscopic evaluation and has
      important clinical value in guiding medical management.

PMID- 18061719
TI  - Starting your first faculty position.

PMID- 18061720
TI  - Endoscopic injection sclerotherapy with doxycycline for mediastinal and
      esophageal lymphangiohemangioma.
AB  - BACKGROUND: Lymphangiohemangioma, also called lymphatic-venous or venolymphatic
      malformation, is a rare malformation of the lymphatics, with vascular elements.
      These are low-flow vascular lesions. OBJECTIVE: To evaluate the feasibility and
      efficacy of endoscopic injection sclerotherapy with doxycycline for low-flow
      vascular malformations in the GI tract. DESIGN: Case report. SETTING: Academic
      center. PATIENTS: An adult man with lymphangiohemangioma that involved the
      mediastinum and the esophagus. The esophageal involvement caused dysphagia and
      chest pain. INTERVENTIONS: We characterized the lesion with EUS and successfully
      treated the esophageal and paraesophageal lesions with endoscopic injection
      sclerotherapy by using doxycycline. MAIN OUTCOME MEASUREMENT: Symptom resolution
      and complications. RESULTS: The patient's esophageal symptoms resolved with
      sclerotherapy. This is the first reported case of lymphangiohemangioma with
      esophageal involvement and the first reported case of endoscopic injection
      sclerotherapy by using doxycycline in the GI tract. LIMITATIONS: Case report and
      short follow-up period. CONCLUSIONS: Endoscopic injection sclerotherapy with
      doxycycline for lymphatic and low-flow vascular malformations in the GI tract is
      feasible, easy, safe, and effective.

PMID- 18061721
TI  - EUS-guided alcohol ablation of left adrenal metastasis from non-small-cell lung
      carcinoma.
AB  - BACKGROUND: EUS presents an alternative access to the left adrenal, making it
      possible to perform echo-guided needle biopsies. OBJECTIVES: We present a case of
      EUS-guided therapy as alcohol ablation of left adrenal metastases. DESIGN AND
      PATIENT: A 52-year-old man was admitted to the hospital complaining of abdominal
      pain. CT scan revealed an invasive process in the left upper lobe of the lung and
      a mass in the left adrenal area that was considered highly suspicious for left
      adrenal metastases from the patient's lung carcinoma. Cytopathologic examination
      of EUS-guided FNA confirmed the diagnosis of left adrenal metastasis. Because the
      patient's main clinical symptom was disabling abdominal pain, we considered the
      possibility of injection of alcohol into the left adrenal metastases under EUS
      guidance to ablate the metastatic lesion and potentially relieve the abdominal
      pain. EUS-guided alcohol ablation was performed successfully. RESULTS AND MAIN
      OUTCOME MEASUREMENT: On follow-up 3 days after EUS-guided left adrenal ablation,
      the patient had no abdominal pain. He remained without abdominal pain after 30
      and 60 days of follow-up. LIMITATION: New technique with limited data.
      CONCLUSION: EUS-guided alcohol ablation of left adrenal metastases in patients
      with non-small-cell lung cancer may provide palliation of cancer-related
      abdominal pain. There may be potential for combining this (minimally invasive and
      easily performed EUS-guided therapeutic) technique for ablation of solitary
      adrenal metastasis in patients with lung cancer with other modalities (e.g.,
      surgery, radiation, or chemotherapy) directed toward the primary pulmonary
      malignancy and adjacent mediastinal disease.

PMID- 18061722
TI  - Pseudodiverticulosis with eosinophilic esophagitis: first reported case.

PMID- 18061723
TI  - Endoscopic closure of a gastrojejunal anastomotic leak (with video).

PMID- 18061724
TI  - Large pancreatic serous cystadenoma presenting with biliary obstruction.

PMID- 18061725
TI  - ERCP plus papillotomy by use of double-balloon enteroscopy after Billroth II
      gastrectomy.

PMID- 18061726
TI  - Simultaneous multitransgastric drainage for large and noncontagious pancreatic
      pseudocysts (with video).

PMID- 18061728
TI  - Hemosuccus pancreaticus caused by metastatic renal cell carcinoma.

PMID- 18061727
TI  - Covered expandable metal stent placement for treatment of a refractory pancreatic
      duct leak.

PMID- 18061729
TI  - Initial experience with hybrid transvaginal cholecystectomy.

PMID- 18061730
TI  - Upper endoscopy in the setting of tongue piercing.

PMID- 18061731
TI  - Gossypiboma successfully removed by upper-GI endoscopy.

PMID- 18061732
TI  - Colonic insufflation and perforation: an opportunity missed.

PMID- 18061734
TI  - Colonoscopy: what can we do to resolve the patient's information gap?

PMID- 18061735
TI  - The use of immediate implant placement for the replacement of a periodontally
      involved malaligned lateral incisor: a clinical report.
AB  - Localized severe chronic periodontitis is often seen in middle-aged patients,
      particularly when plaque control for malaligned teeth is not satisfactory. While
      orthodontic treatment can realign such teeth with reduced periodontal support,
      esthetics may be compromised by gingival recession due to preexisting bone loss
      and resolution of inflammation after periodontal treatment. This clinical report
      describes how a malaligned maxillary lateral incisor with severe periodontitis
      was replaced by an immediately placed implant and implant-supported crown with a
      good esthetic outcome.

PMID- 18061736
TI  - Prosthodontic management of abnormal tooth development secondary to
      chemoradiotherapy: a clinical report.
AB  - Late effects of chemoradiotherapy for childhood cancer treatment include
      developmental disturbances of the maxillofacial and dentoalveolar structures.
      Prosthodontic rehabilitation of these patients presents a significant challenge
      in restoring function, esthetics, and comfort. This clinical report describes the
      prosthodontic management of a young patient who received chemoradiotherapy for
      neuroblastoma and subsequently developed tooth abnormalities. Osseointegrated
      implants and an implant-connecting bar along with an attachment system were used
      to provide retention, support, and stability of a removable mandibular
      overdenture opposing a conventional maxillary complete denture.

PMID- 18061737
TI  - Surface area improvement with grooves and boxes in mandibular molar crown
      preparations.
AB  - STATEMENT OF PROBLEM: Axial-wall inclination has been shown to affect the
      stability of a cemented restoration in function, resulting in early restoration
      failure. PURPOSE: The purpose of this study was to evaluate surface area
      improvement with the use of supplemental grooves in tooth preparations for
      complete crowns. MATERIAL AND METHODS: The surface area preparation improvement
      in combinations of unfavorable/marginal height and axial-wall inclinations was
      quantified. A right regular pyramid was used to simulate a single mandibular
      molar tooth preparation with known axial-wall inclinations and vertical heights.
      Various combinations of these 2 variables allowed the calculation of surface
      areas with a formula for the area of a pyramid, cones, and right triangles
      through geometric/trigonometric manipulations. The pyramidal model system had a 9
      mm square base with marginal and unfavorable vertical heights, 3 or 4 mm, and
      axial-wall inclination angles from 2 to 25 degrees. Conical-shaped grooves of
      varying lengths and widths, depending on height and axial-wall inclinations, were
      introduced with a tapered fissure bur. The percentage of surface area gained or
      lost through the supplementation with tapered grooves and boxes served as the
      dependent variables, alpha-factors (1) through (5). RESULTS: Significant area
      gains were demonstrated in all alpha-level comparisons. The greatest change was
      found in the 4-mm height grouping, as a positive 35.2% gain in the 25-degree
      level with 4 grooves. CONCLUSIONS: Axial-wall groove and box supplementation were
      shown to improve the surface areas of simulated mandibular molar preparations
      with unfavorable axial-wall inclination and vertical height levels.

PMID- 18061738
TI  - The castability of pure titanium compared with Ni-Cr and Ni-Cr-Be alloys.
AB  - STATEMENT OF PROBLEM: Titanium is the most biocompatible metal available for
      dental casting; however, there is great concern about its castability since this
      aspect of a casting metal/alloy has direct influence on the marginal fit of
      dental crowns. PURPOSE: The purpose of this study was to compare the castability
      of commercially pure titanium with 2 Ni-Cr base metal alloys. MATERIAL AND
      METHODS: Castability was evaluated indirectly by determining the sharpness of
      cast crown margins using the lost-wax technique. Castability was expressed in
      terms of the deficiency (mum) between an actual casting margin and a potentially
      perfect margin. Crown margins were recorded in a silicone impression material.
      The degree of marginal rounding was measured and margin length deficiencies (mum)
      were calculated. Sixty acrylic resin crown patterns with wax margins were
      prepared on a stainless steel stylized crown die having a 30-degree beveled
      finish line. The degree of wax margin rounding was determined in the control
      group (group W, n=15). The remaining 45 crown patterns were divided into 3 groups
      (n=15) and cast in commercially pure titanium (Tritan, group Ti), Ni-Cr-Be alloy
      (Verabond; group VB), and Ni-Cr alloy (Verabond II; group VBII). Margin
      configurations for both wax patterns and cast specimens were measured and
      recorded with the same method, using silicone impressions of the margins. After
      polymerization, the silicone material was sectioned in 8 locations through the
      margin area so that cross sections of the margins could be observed. Marginal
      deficiency was determined using microscopic measurements from the silicone
      sections and calculations. Data were subjected to 1-way ANOVA and Tukey HSD test
      (alpha=.05). RESULTS: Statistical analysis showed significant differences among
      the groups W, Ti, VB, and VBII (P<.001). The Tukey test revealed that Ti (108 +/
      26 microm) was not significantly different from VBII (95 +/-35 microm), but was
      significantly different than Groups VB (22 +/-5 microm) and W (19 +/-6 microm),
      which were similar. CONCLUSIONS: Within the limitations of this study, the
      castability of titanium was poor compared to Ni-Cr-Be alloy, but similar to Ni-Cr
      alloy.

PMID- 18061739
TI  - Crown retention and flexural strength of eight provisional cements.
AB  - STATEMENT OF PROBLEM: Few studies have compared the retention of resin-based and
      zinc-oxide noneugenol provisional cements. Crown retention testing is difficult
      and variable; therefore, a simpler method of testing by using flexural strength
      is indicated. PURPOSE: The purpose of this study was to measure the retention of
      base metal alloy castings to dentin provided by 8 provisional cements (3 resin
      based and 5 zinc oxide) and correlate the retention to their flexural strength.
      MATERIAL AND METHODS: Flexural strength specimens (2.5 x 2.5 x 22 mm) were made
      of each cement. The specimens were placed in a 3-point bending testing mode and
      loaded at 1 mm/min until failure. Ten extracted teeth were milled to a
      standardized complete crown preparation, fitted with Rexillium III castings, and
      cemented with each provisional cement. The specimens were subjected to a tensile
      load (1 mm/min) until failure in a universal testing machine. The flexural
      strength for each cement was calculated in MPa and correlated to the retention. A
      1-way ANOVA and Tukey HSD post hoc analysis were used to determine significant
      intergroup differences (alpha=.05). Linear regression was used to correlate
      flexural strength and crown retention (alpha=.05). RESULTS: Significant
      differences were found in the flexural strengths and retention provided by the
      various cements. Flexure strength was correlated with cement retention for resin
      based cements (r=0.998) but not zinc-oxide noneugenol cements (r=0.058).
      CONCLUSIONS: Based on a 20-degree preparation, stronger cements provide increased
      retention. Therefore, the desired amount of retention should be based on both the
      cement and a clinical evaluation of the preparation.

PMID- 18061740
TI  - Bacterial adhesion of Streptococcus mutans to provisional fixed prosthodontic
      material.
AB  - STATEMENT OF PROBLEM: Bacterial adhesion and formation of dental plaque on
      provisional fixed prosthodontic materials results in gingival inflammation and
      secondary caries. PURPOSE: The purpose of this in vitro study was to compare 10
      commonly used provisional fixed prosthodontic materials (2 acrylic polymethyl
      methacrylates, 2 improved methacrylates, and 6 bisacrylate composite resins),
      based on their susceptibility to adhere to Streptococcus mutans, and examine the
      influence of surface roughness and hydrophobicity. MATERIAL AND METHODS: Surface
      roughness was assessed by perthometer and hydrophobicity by contact angle
      measurements. Streptococcus mutans suspension was incubated with 15 disk-shaped
      specimens for each material (10 x 2 mm) and examined with the fluorescence dye,
      Alamar Blue/resazurin, and an automated multidetection reader. Glass and the
      veneering composite resin, Sinfony, served as controls. Statistical analysis was
      performed using the Mann-Whitney U-test in combination with the Bonferroni
      adjustment. Additionally, scanning electron micrographs were made. RESULTS:
      Median surface roughness values ranged between 0.04 microm and 0.08 microm, and
      median contact angles between 46.5 and 71 degrees. High relative fluorescence
      intensities (>10,000) were found for Snap, UniFast LC, and CronMix K plus,
      moderate values (5000-10,000) for Trim, Temphase, Structur Premium, and PreVISION
      CB, and lowest fluorescence intensities (<5000) were found for Cronsin, Protemp 3
      Garant, and Luxatemp. Scanning electron micrographs displayed streptococcal
      monolayers on all investigated surfaces, indicating initial bacterial adhesion.
      CONCLUSIONS: The quantity of bacterial adhesion differed significantly among the
      assessed provisional materials. A correlation between bacterial adhesion and
      surface roughness or hydrophobicity was not confirmed. Bisacrylate composite
      resins and acrylic polymethyl methacrylates had significantly lower adhesion
      potentials than improved methacrylates.

PMID- 18061741
TI  - Effect of implant-supported or retained dentures on masticatory performance: a
      systematic review.
AB  - STATEMENT OF PROBLEM: While subjective patient-based measures have been
      increasingly recognized as critical outcomes for prosthodontic treatment, there
      continues to be a need to validate for patients what changes in masticatory
      function can be expected with the provision of new implant-supported or retained
      dentures. PURPOSE: The purpose of this review was to evaluate the critical
      factors impacting change in masticatory performance following the provision of
      new implant-supported or retained dentures. MATERIAL AND METHODS: Information
      retrieval followed a systematic approach using PubMed and the Cochrane Library.
      English articles published from 1966 to June 2007, in which the masticatory
      performance of subjects with implant-supported or retained dentures was assessed
      by objective methods and compared to performance with conventional dentures, were
      included. Ratings of the evidence provided in each article followed United States
      Agency for Healthcare Research and Quality recommendations. RESULTS: From 281
      articles identified, 18 peer-reviewed articles met prespecified criteria for
      inclusion. Specific outcomes of significance identified by these articles rated
      as level II are: (1) fixed implant-supported partial dentures do not provide
      significant improvement in masticatory performance compared to conventional
      removable partial dentures for Kennedy Class I and II partially edentulous
      mandibles; (2) the combination of a mandibular implant-supported or retained
      overdenture (IOD) and maxillary conventional complete denture (CD) provides
      significant improvement in masticatory performance compared to CDs in both the
      mandible and maxilla for a limited population having persistent functional
      problems with an existing mandibular CD due to severely resorbed mandible; and
      (3) the type of implant and attachment system for mandibular IODs has a limited
      impact. Specific outcomes of significance identified by articles rated as having
      a moderate level of evidence (level III) are: (1) mandibular fixed implant
      supported complete dentures provide significant improvement in masticatory
      performance compared to mandibular CDs in subjects dissatisfied with their CDs;
      and (2) implant-supported mandibular resection dentures have an advantage over
      conventional dentures in masticatory performance on the defect side of the mouth.
      CONCLUSIONS: Objective benefits in masticatory performance of implant-supported
      or retained dentures compared to conventional dentures are limited to a
      mandibular IOD in edentulous patients with a resorbed mandible and/or difficulty
      adapting to CDs.

PMID- 18061742
TI  - Fabrication of an all-ceramic abutment crown under an existing removable partial
      denture using CAD/CAM technology.
AB  - Fabricating a crown beneath an existing removable partial denture is technique
      sensitive, difficult, and time consuming. A procedure is described using CAD/CAM
      technology to fabricate an all-ceramic crown under an existing removable partial
      denture that is simple, esthetic, and convenient for the patient and the
      clinician.

PMID- 18061743
TI  - A modified putty-wash vinyl polysiloxane impression technique for fixed
      prosthodontics.

PMID- 18061744
TI  - The milled ceramic post and core: A functional and esthetic alternative.

PMID- 18061745
TI  - Do sleep deprivation and alcohol have the same effects on psychomotor
      performance?

PMID- 18061746
TI  - Perception of simulated driving performance after sleep restriction and caffeine.
AB  - OBJECTIVE: As feelings of alertness are reported to be highly correlated with
      performance perception, the objective of this study was to determine whether
      caffeine, a common countermeasure to driver sleepiness, affected a sleepy
      driver's ability to monitor his or her simulated driving performance. METHODS:
      Twelve healthy young adults (six males, six females) participated in three
      counterbalanced, blinded, daytime conditions: control [9 h time in bed (TIB)],
      100 mg caffeine (4 h TIB), and placebo (4 h TIB). Driving performance was
      measured through lane drift on a series of 30-min simulated driving sessions.
      Subjective sleepiness and perception of driving performance were measured at 5
      min intervals during driving sessions via the Karolinska Sleepiness Scale and a
      corresponding perception scale. RESULTS: Sleep restriction had a significant
      detrimental effect on driving performance and subjective measures. Caffeine
      resulted in significant improvements across all measures. Subjective measures
      were found to be significantly correlated after sleep restriction and prior to
      caffeine. Correlations between actual and perceived performance were
      nonsignificant across all conditions. CONCLUSIONS: The strong correlation between
      subjective measures supports the postulation that sleepiness is used as a cue for
      performance prediction when sleep restricted. The relationship between perceived
      and actual performance after fatigue countermeasures remains inconclusive.
      Further research, addressing limitations, is needed.

PMID- 18061747
TI  - Sleep preoccupation in poor sleepers: psychometric properties of the Sleep
      Preoccupation Scale.
AB  - OBJECTIVES: Despite daytime factors being implicated as having a key perpetuating
      role in many of the recent cognitive models of sleep disturbance, standardized,
      validated measures of sleep-related daytime processing are rare. The aim of the
      present studies was to develop, refine, and psychometrically evaluate the Sleep
      Preoccupation Scale (SPS), a self-report tool that examines levels of daytime
      sleep-related processing. METHODS: The SPS is constructed using a quantitative
      content analysis of responses from a survey of older adults (n=116). The scale is
      then refined using principal components analysis on a general population sample
      (n=456), and finally, the convergent validity is examined in a general population
      sample (n=722). RESULTS: The results suggest the SPS is a reliable and valid
      measure of sleep-related daytime processing and discriminates different sleeper
      groups (poor, average, and good sleepers). CONCLUSION: The findings are related
      to the models of poor sleep and, in particular, insomnia, and future directions
      are discussed.

PMID- 18061748
TI  - Parent reports of sleep/alertness problems and ADHD symptoms in a sample of obese
      adolescents.
AB  - OBJECTIVE: Recent evidence suggests an association between obesity and Attention
      Deficit/Hyperactivity Disorder (ADHD) or ADHD traits. The characteristics of
      obese subjects with a higher probability of ADHD symptoms are still unclear. We
      explore the hypothesis that obese adolescents with sleep/alertness problems
      represent a subgroup at high risk for ADHD traits, independently from associated
      symptoms of anxiety/depression. The aim of this study was to assess the
      relationship between parent reports of sleep/alertness problems and ADHD traits
      in a clinical sample of obese adolescents, controlling for symptoms of
      anxiety/depression. METHODS: Seventy obese subjects (age range, 10-16 years) were
      included. The parents filled out the Sleep Disturbance Scale for Children (SDSC),
      the Conners Parents Rating Scale-Revised (Short Version) (CPRS-R:S), and the
      Child Behavior Checklist (CBCL). The ADHD Rating Scale (ADHD-RS) was completed by
      a child psychiatrist. RESULTS: Using multiple regression models controlling for
      symptoms of anxiety/depression, scores of excessive daytime sleepiness on the
      SDSC were significantly associated with ADHD traits on the CPRS-R:S as well as on
      the ADHD-RS. CONCLUSIONS: Obese adolescents described as excessively sleepy by
      their parents may be at higher risk of ADHD symptoms, independently from symptoms
      of anxiety/depression. Although the clinician may overlook a potential diagnosis
      of ADHD in obese adolescents described as sleepy, the results of this study
      suggest to systematically look for symptoms of ADHD in this subgroup of obese
      patients. Further studies using objective methods to assess sleep/alertness
      disturbances are needed to gain insight into the relationship between
      sleep/alertness disturbances and ADHD in obese individuals.

PMID- 18061749
TI  - Restless legs syndrome, insomnia, and quality of life after renal
      transplantation.
AB  - OBJECTIVE: Restless legs syndrome (RLS) is associated with insomnia and impaired
      quality of life (QoL) in patients on maintenance dialysis; however, no
      information has been published on the association of RLS and QoL in kidney
      transplanted patients. In a cross-sectional study, we analyzed the complex
      relationship between RLS, insomnia, and health-related QoL in kidney-transplanted
      patients. METHODS: In a cross-sectional survey at a single transplant center,
      1067 patients were invited to participate. Complete data set was available from
      785 kidney-transplanted patients. The RLS Questionnaire and the Athens Insomnia
      Scale were used to assess the prevalence of RLS and insomnia, respectively. QoL
      was measured using the Kidney Disease QoL-SF Questionnaire. RESULTS: Patients
      with RLS were three times more likely to have insomnia than patients without RLS
      (29% vs. 9%, P=.001), and the presence of RLS was a significant and independent
      predictor of insomnia in multivariate analysis. The presence of RLS was
      independently associated with impaired health-related QoL along several QoL
      domains after statistical adjustment for clinical and sociodemographic
      covariables. Importantly, this association remained significant even after
      adjusting for insomnia for some QoL domains. CONCLUSION: RLS is associated with
      poor sleep, increased odds for insomnia, and impaired QoL in kidney-transplanted
      patients. Our results suggest that both sleep-related and sleep-independent
      factors may contribute to the association of RLS and QoL.

PMID- 18061750
TI  - Neurocognitive changes after carotid revascularization: a review of the current
      literature.
AB  - OBJECTIVE: The objective of this study was to review the current literature
      evaluating the effect of carotid revascularization on neurocognitive function.
      METHODS: A PubMed search was performed using the following keywords: carotid
      surgery, carotid stenosis, cognition, and cognition disorders. Bibliographies
      were cross referenced and related-articles searches were performed once an
      article of interest had been identified. RESULTS: Twenty-two studies have been
      identified from the literature since 1998. Seventeen articles evaluated carotid
      endarterectomy (CEA), four evaluated carotid stenting, and one compared CEA to
      stenting. Eight studies found improvements in mood and/or cognition after
      revascularization, 11 studies showed mixed results, and 3 studies found declines.
      CONCLUSIONS: There is no consensus within the current literature as to the effect
      of carotid revascularization on neurocognitive function. Further research--with
      attention to laterality of neurocognitive effects, patients' symptomatology at
      the time of presentation, the role of perioperative embolization, and trial
      design including adequate control groups and comparison between open surgery and
      stenting factors--is necessary in order to clarify the effects of carotid
      revascularization on cognition.

PMID- 18061751
TI  - Neurocognitive disability, stroke, and surgery: a role for neuroergonomics?

PMID- 18061752
TI  - Quality of life among patients with a brain tumor and their carers.
AB  - OBJECTIVE: This study assessed the quality of life and psychosocial well-being of
      brain tumor patients and their carers. METHODS: A cross-sectional postal survey
      was completed by 75 patients and 70 carers (response rate=29.8%) who were listed
      in a community-based brain tumor support group database. Measures used were the
      Functional Assessment of Cancer Therapy-General (FACT-G) and the Hospital Anxiety
      and Depression Scale (HADS). Queensland population-based norms for the FACT-G
      were used for comparison. RESULTS: On average, as compared with population norms,
      the FACT-G summary scores of the patients (mean=74.6, S.D.=18.6) and carers
      (mean=76.7, S.D.=17.7) were between 0.5 and 1 S.D. lower, representing a
      clinically significant reduction in their quality of life. Among patients and
      carers, 30% and 40%, respectively, reported anxious moods and 17% and 10%,
      respectively, reported depressed moods on the HADS. Significant correlations were
      observed between the FACT-G and HADS subscales, particularly emotional well-being
      and anxiety, as well as physical and functional well-being and depression, and
      between patients' and their carers' quality of life. Among the patients,
      predictors of lower quality of life were older age and female sex, whereas for
      the carers, there was a trend for lower quality of life among those looking after
      a patient with a high-grade disease. CONCLUSIONS: The degree of detriment to
      quality of life by a brain tumor for patients and that for their carers are
      similar and clinically significant. The association between the FACT-G subscales
      and the HADS indicates that improvements could be achieved by alleviating
      emotional distress and improving functional well-being.

PMID- 18061753
TI  - Tailored psychotherapy for patients with functional neurological symptoms: a
      pilot study.
AB  - OBJECTIVE: The objective of this study was to assess whether individually
      tailored psychotherapy for patients with functional neurological symptoms is
      associated with improvements in patient-centered measures of emotional well
      being, quality of life, as well as somatic symptoms and whether this treatment
      modality is likely to be cost-effective. METHODS: We conducted an uncontrolled
      prospective pilot study of consecutive patients with functional symptoms referred
      from neurology outpatient clinics to a single psychotherapist using validated
      questionnaires [Clinical Outcomes in Routine Evaluation Outcome Measure (CORE
      OM), Short Function (SF)-36 Health Survey, and Patient Health Questionnaire (PHQ)
      15]. Patients had a median of 6 treatment sessions (range=1-24). Ninety-one
      patients completed questionnaires at referral, 63 did at the end of treatment,
      and 34 did at follow-up after 6 months. Significant improvements were seen on all
      measures and were maintained at follow-up (CORE-OM, P=.003; SF-36, P<.001; PHQ
      15, P=.001). Significance was not lost in an intention-to-treat analysis. Of all
      the patients, 49.2% improved by at least 1 S.D. in at least one of the measures.
      The number of patients needed to be treated to see an improvement of at least 1
      S.D. in one of the three outcome measures was 2; that in two measures, 3.9; and
      that in all measures, 7. The mean cost of the intervention was pound231; the cost
      per quality-adjusted life year was estimated as pound5,328. RESULTS:
      Psychotherapy was associated with significant improvements in patient-centered
      measures, which seemed to be achieved at a comparatively low cost. CONCLUSIONS:
      The results indicate that psychotherapy may be a cost-effective intervention for
      patients presenting with functional neurological symptoms. The findings warrant
      further assessment of this treatment with a randomized and controlled trial.

PMID- 18061754
TI  - Treating patients with functional symptoms: one size does not fit all.

PMID- 18061755
TI  - Cognitive complaints after mild traumatic brain injury: things are not always
      what they seem.
AB  - OBJECTIVE: To compare nonreferred, emergency department (ED)-admitted mild
      traumatic brain injury (MTBI) patients with and without self-reported cognitive
      complaints on (1) demographic variables and injury characteristics; (2)
      neuropsychological test performance; (3) 12-day self-monitoring of perceived
      cognitive problems; and (4) emotional distress, physical functioning, and
      personality. METHODS: (Neuro)psychological assessment was carried out 6 months
      post-injury in 79 patients out of a cohort of 618 consecutive MTBI patients aged
      18-60, who attended the ED of our level I trauma centre. Cognitive complaints
      were assessed with the Rivermead Postconcussional Symptoms Questionnaire (RPSQ).
      In addition, patients monitored concentration problems and forgetfulness during
      12 consecutive days. RESULTS: Self-reported cognitive complaints were reported by
      39% of the patients. These complaints were strongly related to lower educational
      levels, emotional distress, personality, and poorer physical functioning
      (especially fatigue) but not to injury characteristics. Severity of self-reported
      cognitive complaints was neither associated with the patients' daily observations
      of cognitive problems nor with outcome on a range of neuropsychological tests.
      CONCLUSION: Self-reported cognitive complaints were more strongly related to
      premorbid traits and physical and emotional state factors than to actual
      cognitive impairments. In line with previous work, this suggests that treatment
      of emotional distress and fatigue may also reduce cognitive complaints. Cognitive
      outcome assessment of symptomatic MTBI patients should not be restricted to
      checklist ratings only, but also include a (neuro)psychological screening. In
      addition, daily monitoring of complaints is a useful method to gather information
      about the frequency and pattern of cognitive problems in daily life.

PMID- 18061756
TI  - Relaxation and guided imagery program in patients with breast cancer undergoing
      radiotherapy is not associated with neuroimmunomodulatory effects.
AB  - OBJECTIVE: Treatment of breast cancer is usually associated with significant
      psychological stress. In this study, we examined the effects of relaxation and
      visualization therapy (RVT) on psychological distress, cortisol levels, and
      immunological parameters of breast cancer patients undergoing radiotherapy.
      METHODS: Participants were randomly assigned to either the experimental (n=20)
      who underwent group RVT for 24 consecutive days or control group (n=14) who were
      on radiotherapy only. Psychological scores (stress, anxiety, and depression) were
      measured by structured clinical interviews. Salivary cortisol was assessed along
      the day. Lymphocytes were isolated and cultured to measure T-cell proliferation
      and sensitivity to glucocorticoids (GCs). RESULTS: RVT was effective to reduce
      stress, anxiety, and depression scores (all P<.05). However, cortisol levels as
      well as proliferation remained unchanged following RVT. Although T cells of
      experimental group were more sensitive to GCs than cells of controls at baseline,
      no changes were noted following RVT. Cortisol levels were positively correlated
      to anxiety and depression scores and inversely correlated to T-cell proliferation
      and sensitivity to GCs. CONCLUSION: We conclude that the psychological
      intervention was capable to attenuate the emotional distress presented during
      radiotherapy treatment. A longer RVT or worse psychological morbidity at baseline
      may be necessary to translate psychological into biological changes.

PMID- 18061757
TI  - Trauma experience in individuals with idiopathic environmental intolerance and
      individuals with somatoform disorders.
AB  - OBJECTIVE: Results from previous studies suggest that past trauma experience
      increases the risk for medically unexplained somatic symptoms and somatoform
      disorders (SFD). This cross-sectional study examined the link between various
      lifetime traumas, idiopathic environmental intolerance (IEI), and SFD. METHODS:
      Two clinical groups of 54 subjects with IEI and 44 subjects with SFD were
      compared to 54 subjects (comparison group, CG) free from both IEI and SFD
      regarding self-reported traumas. The subjects were mainly recruited via
      advertisements in local newspapers. From 970 individuals screened for IEI and
      multiple somatic symptoms, 152 were included through a two-step selection
      procedure consisting of screening questionnaires, a medical examination, and
      structured interviews for IEI and mental disorders. RESULTS: In all three groups
      at least one potential traumatic event was reported rather frequently (CG: 70%;
      IEI: 82%; SFD: 73%). But contrary to our expectation, significant group
      differences were neither found in regard to the proportion of subjects with any
      trauma, nor traumas fulfilling DSM-IV criteria (CG: 41%; IEI: 48%; SFD: 59%), nor
      multiple traumas (CG: 43%, IEI: 56%, SFD: 39%). Only two trauma categories were
      endorsed more frequently by the two clinical groups than by the CG: the
      unspecified 'other' category (IEI, SFD>CG) and 'life-threatening illness'
      (IEI>CG). CONCLUSION: No clear evidence was found for increased rates of trauma
      experience in IEI and SFD. However, the results of this exploratory study should
      be considered as preliminary. Comparing larger IEI and SFD groups with a
      representative population-based sample may yield different results.

PMID- 18061758
TI  - Memory bias for health-related information in somatoform disorders.
AB  - OBJECTIVE: Cognitive processes are considered to be relevant to the etiology and
      maintenance of somatoform disorders (SFDs). The aim of this study was to assess
      explicit and implicit information-processing bias for disorder-congruent
      information in SFDs. METHODS: A clinical sample of 33 patients suffering from
      multiple somatoform symptoms (SSI-3/5) and 25 healthy controls performed an
      encoding task with computer-presented word lists (illness related, negative,
      positive, neutral content), subsequently followed by explicit memory tests (free
      recall and recognition) and an implicit test (word-stem completion). RESULTS: The
      somatoform group showed a memory bias for illness-related stimuli in the word
      stem completion task, whereas the two groups did not differ in explicit memory
      tests. This effect could not be explained by comorbid depression. CONCLUSION:
      These results provide some support for current theories on SFDs.

PMID- 18061759
TI  - A sensitive body or a sensitive mind? Associations among somatic sensitization,
      cognitive sensitization, health worry, and subjective health complaints.
AB  - OBJECTIVES: Psychobiological sensitization and health worry appear to be involved
      in the etiology of clinical manifestations of subjective health complaints (SHCs)
      via amplified processing of health-related information. However, it is not clear
      whether sensitization and health worry are also associated with common SHCs,
      which are extremely prevalent and are responsible for a large part of both human
      suffering and health care costs. In this study, we investigated whether SHCs are
      associated with health worry and two types of sensitization: cognitive health
      related sensitization and somatic sensitization. We also examined whether health
      worry mediates the relationship between cognitive sensitization and SHCs and
      whether both levels of sensitization interact. METHODS: A nonclinical sample of
      47 female students completed questionnaires about their recent subjective health
      as well as health worry and underwent tests for cognitive sensitization,
      operationalized as Stroop interference and free recall performance, and somatic
      sensitization, operationalized as pain tolerance and pain threshold in a cold
      pressor task. RESULTS: Severity of health complaints was positively related with
      recall of health-related stimuli, but not with Stroop interference, and with
      worrying about health complaints. In addition, worry mediated the relationship
      between recall bias and severity of health complaints. Both the number and
      severity of recent health complaints were associated with pain tolerance. Pain
      threshold was associated with Stroop interference for health-related information.
      CONCLUSIONS: The results suggest that specific types of cognitive sensitization
      and somatic sensitization are associated with common health complaints and that
      worrying about one's complaints might play a role by enhancing biased memory of
      health-related information.

PMID- 18061760
TI  - Traditional ecological knowledge (TEK) and scientific weight of evidence
      determinations.

PMID- 18061762
TI  - Ancillary services available to the orthopedic surgeon.
AB  - The delivery of high quality medical services is approaching a crisis situation
      in the United States. As physician reimbursements decline and overhead increases,
      orthopedic surgeons must seek additional sources of revenue to remain financially
      viable and control the quality of medical care that they deliver. The orthopedic
      surgeon group is well positioned to control its own service lines and deliver
      excellent patient care as a result. This article reviews the possibilities of
      multiple types of ancillary service lines available for the orthopedic group
      practice.

PMID- 18061763
TI  - How to perform a feasibility study and market analysis to determine if an
      ancillary service makes sense.
AB  - A feasibility study, as the name implies, is a study of the viability of a
      business venture. The study is an analysis of the market potential of the new
      products or services to be offered and investigates the primary issues related to
      the new business. This article discusses the elements that are essential for a
      valid feasibility study.

PMID- 18061764
TI  - Pros and cons of the ambulatory surgery center joint venture.
AB  - If a physician group has determined that it has a realistic patient base to
      establish an ambulatory surgery center, it may be beneficial to consider a
      partner to share the costs and risks of this new joint venture. Joint ventures
      can be a benefit or liability in the establishment of an ambulatory surgery
      center. This article discusses the advantages and disadvantages of a hospital
      physician-group joint venture.

PMID- 18061765
TI  - Developing an orthopedic ambulatory surgery center.
AB  - Although there are risks, the potential benefits should encourage one to consider
      developing an orthopedic ambulatory surgery center (OASC). Patients should
      appreciate the enhanced care they experience at a surgery center. The orthopedist
      can enjoy the benefits of increased income, time savings, and productivity
      provided by the surgery center. This article discusses the complex and time
      consuming demands of developing the OASC, and having it operate efficiently. It
      points out how experts can assist in developing and managing a highly efficient
      center, freeing the orthopedist to concentrate on performing surgery in an
      environment that is clinically, financially, and personally rewarding.

PMID- 18061766
TI  - Financing and cash flow management for the medical group practice.
AB  - The expansion of a medical group practice and the addition of ancillary services
      require a substantial cash outlay. Obtaining proper financing to complete a
      successful expansion is a process that takes time, and there are critical steps
      that must be followed. The group's business objectives must be presented properly
      by developing a business plan detailing the practice and goals associated with
      the desired expansion. This article discusses some of the key elements that are
      essential in creating an overall effective business plan for the group medical
      practice.

PMID- 18061767
TI  - Gain-sharing with the hospital: what is possible in the current legal
      environment.
AB  - This article focuses on the idea of gain-sharing, defined as engagement between
      the hospitals and physician to create effective joint processes, common outcome
      measures, joint accountability, and a sharing of results. Gain-sharing is a
      logical approach to addressing fragmented care, cost containment, and improved
      clinical outcomes. In particular, this article focuses on contracts under which a
      hospital or institutional provider retains an independent clinic or physicians to
      tackle specific issues of service line performance.

PMID- 18061768
TI  - The physician-owned imaging center.
AB  - The advent of advanced imaging modalities in the past 20 years represents a
      paradigm shift as physicians seek new ways to offer earlier diagnosis and
      treatment and to augment practice service and revenues. A physician-owned, office
      based imaging project has evolved from conventional X ray to more advanced
      imaging, which includes MRI, CT, and other digital imaging methods. Orthopedic
      practices need to do a thorough analysis to match the technology and type of unit
      to the patient volume and prospective payment for the services rendered. This
      analysis should include understanding the capability and limitations of the MRI
      or other imaging modality selected, staffing, siting, and teleradiology
      interpretations. This article elucidates this general trend in orthopedic imaging
      and examines practical aspects of the physician/practice-owned imaging center.

PMID- 18061769
TI  - The physician-owned physical therapy department.
AB  - As the trend toward shrinking reimbursement for physician services continues, an
      internal physical therapy clinic providing high-quality care and a source of
      additional revenue presents an attractive opportunity. Internalization of
      physical therapy services within the clinic as either an off-site or on-site
      entity can assure patient access to the highest quality of rehabilitation
      services under the group's supervision and direction. It will contribute
      positively to creating patient loyalty to and confidence in their physician and
      physical therapist. This article discusses the issues that are important to
      address in creating a physician-owned physical therapy department.

PMID- 18061770
TI  - The physician-owned occupational health department.
AB  - This article provides a process to evaluate the likelihood of establishing a
      financially viable occupational medicine program (OMP), and discusses
      opportunities in which the occupational medicine clinic can partner with
      employers to help them to reduce the occurrence of work-related injuries and
      provide a safer work environment. Not all germane topics are discussed-employers
      must address safety and ergonomic issues within the workplace as well as those
      that a successful OMP is designed to address. However, the OMP should be a
      readily available resource for any of these issues. Common occupational
      challenges and opportunities also are examined.

PMID- 18061771
TI  - The physician-owned orthotic and durable medical equipment service.
AB  - In recent years, orthopedic practices have been forced to create internal
      ancillary profit centers to help compensate for escalating operating expenses.
      Increased professional liability premiums and health care costs, coupled with
      decreased reimbursements, have made the development of these ancillary centers a
      necessity. Practices that assess and incorporate sound business policies in
      developing the entity, monitor its progression, and strive to enhance the overall
      offerings within the division will derive the most profitability. By following a
      structured plan, practices can maximize revenue potential and improve patient
      satisfaction and outcomes. This article describes how to construct and follow
      such a plan.

PMID- 18061772
TI  - Medical opinions: the physician-owned independent medical examination company.
AB  - This article discusses the factors that contribute to the success of an
      independent medical examination company. It considers opportunity costs, the
      regulatory environment, the assessment of the competition and the customer base,
      and marketing principles. It also details the management expertise and the staff
      skill sets required for a successful venture.

PMID- 18061773
TI  - Legal issues affecting ancillaries and orthopedic practice.
AB  - The federal and state governments have imposed significant regulations on health
      care generally and on ancillary services in particular. This article focuses on
      how state and federal laws shape the ability of an orthopedic physician to offer
      ancillary services, whether as an individual, through a group practice, or as
      part of a joint venture. It focuses on how the Stark law, the Medicare anti
      kickback statute, state anti-kickback, fee-splitting provisions, certificate of
      need laws, and various Medicare billing and supervision requirements impact the
      provision of ancillary services. It also briefly discusses how physicians should
      prepare for and respond to government investigations.

PMID- 18061774
TI  - The attack on ancillary service providers at the federal and state level.
AB  - The health care delivery system in the United States has witnessed more dramatic
      changes during the last decade than it had since the passage of Medicare. The
      managed care revolution and changes in reimbursement for Medicare services have
      forced providers to look for more efficient ways to provide services as well as
      for additional sources of revenue- and margin-producing business. The move toward
      specialized inpatient and outpatient facilities, often owned by physicians, is a
      natural reaction to these significant changes. These developments have resulted a
      "turf war" between physicians and hospitals over who should control these
      revenues.

PMID- 18061775
TI  - Making the electronic medical record work for the orthopedic surgeon.
AB  - This article explores the current reasons why orthopedic surgeons might consider
      the adoption of an electronic medical record system in their practices today. The
      costs and benefits as well as the barriers to implementation are discussed.

PMID- 18061776
TI  - Putting it all together: the efficient, profitable orthopedic practice.
AB  - In today's complex practice environment, the orthopedic surgeon is faced with
      multiple stressful practice decisions. To achieve a surgeon's personal practice
      goals of quality of care, quality of life, and improvement in quality of
      practice, the physician must commit himself or herself to a certain amount of
      restructuring of his or her practice. This article describes the elements
      necessary for successful restructuring.

PMID- 18061778
TI  - Complimentary and alternative medicine. Preface.

PMID- 18061780
TI  - Herbs to homeopathy-medicinal products for children.
AB  - Many pediatric patients and their families use dietary supplements and
      homeopathy. They do not always disclose this information to their health care
      practitioners. It is important that health care practitioners are aware of the
      research available in these areas and discuss the use of these products openly
      with their patients. As part of that dialogue, clinicians need to consider what
      level of effectiveness is acceptable to support the use of these products by
      their patients. This risk-benefit appraisal should consider safety,
      effectiveness, the medical condition being treated, and the personal beliefs and
      preferences of patients and their families.

PMID- 18061779
TI  - Primary care from infancy to adolescence.
AB  - The use of complementary and alternative medical (CAM) therapies is increasing
      among well children and adolescents and in those children who have special health
      care needs. Integrative pediatrics, a holistic practice that includes an examined
      integration of CAM and conventional therapies, is ideally suited for primary
      care. This article describes how to integrate evidence-based CAM therapies for
      colic, atopy, ADHD, eating disorders, and other conditions commonly seen in
      primary care practice.

PMID- 18061781
TI  - Ethics of complementary and alternative medicine use in children.
AB  - Complementary and alternative medicine (CAM) has enjoyed tremendous public
      interest in North America in recent years. CAM is used most often by those who
      have serious, chronic, or recurrent illness, sometimes for symptom control and
      sometimes to combat the primary disease. Others use CAM to promote wellness or as
      a prophylaxis. CAM therapies are increasingly being offered in conventional
      medical settings and at various other centers and institutes. The relevant
      ethical commitments or values that must be considered are social commitment to
      public welfare, nonmaleficence, respect for patient autonomy/consumer choice,
      recognition of medical pluralism, and public accountability. This article
      explores the major ethical principles involved in pediatric CAM use and how they
      affect clinical care and research.

PMID- 18061782
TI  - Acupuncture for pediatric pain and symptom management.
AB  - Over 2 million people in the United States are estimated to use acupuncture
      annually, primarily for musculoskeletal complaints and pain management, evidence
      that the integration of acupuncture into Western health care is increasing.
      Despite the increase in the quality of trials demonstrating the efficacy and
      safety of acupuncture in medicine, the pediatric acupuncture literature lacks the
      quantity and quality of the same body of evidence. Contributing to this paucity
      of evidence may be the acceptability of acupuncture in pediatric patients. There
      is an urgent need for high-quality randomized controlled trials on the use of
      acupuncture in the pediatric population. This review aims to highlight the
      evidence for use of acupuncture in pain and symptom management.

PMID- 18061784
TI  - Integrative approaches to childhood constipation and encopresis.
AB  - Constipation and encopresis (fecal soiling) are common childhood disorders that
      may lead to significant functional impairment. The etiology and course of
      constipation and encopresis are increasingly conceptualized from a broad
      biopsychosocial perspective, and therefore a holistic approach to assessment and
      treatment is indicated. Many children experience symptoms of chronic constipation
      and/or encopresis that are only partially responsive to conventional medical
      therapy. Complementary/alternative therapies can often help in the treatment of
      constipation/encopresis and are well accepted by patients and families.

PMID- 18061785
TI  - Probiotics in children.
AB  - The gastrointestinal flora plays a complex and important role in the development
      of healthy immunologic and digestive function in children. Probiotics are safe in
      healthy children and effective in reducing the risk of antibiotic-associated
      diarrhea and the duration of acute infectious diarrhea. Probiotics may also be
      effective in preventing community-acquired diarrheal infections, in reducing the
      risk of necrotizing enterocolitis in premature infants, and in the prevention and
      treatment of atopic dermatitis. The exact strain or combination of strains most
      effective for common clinical indications has yet to be determined, but the exact
      strain used seems less important than whether an adequate dose is used (typically
      5 to 10 billion CFUs per day or higher). Clinicians should familiarize themselves
      with the products available because there is a wide range in their quality.

PMID- 18061786
TI  - Integrative approach to obesity.
AB  - Integrative medicine blends conventional medicine with carefully evaluated
      complementary therapies and considers all elements of a patient's lifestyle
      (physical, mental, spiritual). Integrative medicine therapies and philosophies
      have characteristics similar to those of successful treatment programs for
      pediatric obesity. This article defines pediatric obesity and explores those
      similarities in more detail. It also updates the practitioner on selected
      integrative approaches as they relate to prevention and treatment of pediatric
      obesity.

PMID- 18061783
TI  - Complementary and alternative medicine therapies to promote healthy moods.
AB  - Pediatric mood disorders (unipolar depression and bipolar disorder) are serious,
      common, persistent, and recurrent medical conditions. Depression is the second
      leading cause of illness and disability among young people worldwide. A healthy
      lifestyle and healthy environment are the cornerstones for promoting positive
      moods. In addition, several complementary therapies, including nutritional
      supplements, herbs, mind-body therapies, massage, and acupuncture can be helpful.
      The focus of this article is the fundamental lifestyle approaches and
      complementary therapies that enhance mental health in young people. Various
      resources are available to clinicians to help patients and families promote
      mental health.

PMID- 18061787
TI  - Complementary and alternative medical therapies for attention
      deficit/hyperactivity disorder and autism.
AB  - Complementary and alternative medical (CAM) therapies are commonly used by
      parents for their children who have attention deficit hyperactivity disorder
      (ADHD) or autism spectrum disorders. The use of these therapies is well
      documented, yet the evidence of the safety and efficacy of these treatments in
      children is limited. This article describes the current evidence-based CAM
      therapies for ADHD and autism, focusing on nutritional interventions; natural
      health products, including essential fatty acids, vitamins, minerals, and other
      health supplements; biofeedback; and reducing environmental toxins. The CAM
      evidence in ADHD is addressed, as is the CAM literature in autism.

PMID- 18061788
TI  - Integrative medicine and asthma.
AB  - Childhood asthma is a spectrum of symptoms and clinical presentations. The
      treatment begins with developing goals of therapy for a child by the health care
      provider, the family, and the child as a team. The primary objective is to reduce
      symptoms and exacerbations using therapies that include conventional medications,
      environmental controls, and lifestyle modification while reducing the potential
      for adverse effects of medications and the disease. Complementary and alternative
      medicine (CAM) may play a role in meeting these objectives, and through the
      integration of conventional and CAM therapies, an integrative medicine approach
      may facilitate reaching these objectives in a more effective manner.

PMID- 18061789
TI  - Pediatric massage therapy: an overview for clinicians.
AB  - Pediatric massage therapy (MT), similar to its younger counterpart infant
      massage, has a limited number of rigorous studies supporting its clinical
      application and associated effects. However, clinicians and researchers have been
      intrigued by the potential benefits of pediatric MT for improving psychological
      and physiologic states in children who have various health conditions. This
      article provides a broad overview of pediatric MT, including proven and promising
      effects of MT across disease-specific clinical applications, contraindications,
      safety, context and availability of services, and future directions. Computerized
      databases were searched for relevant studies, including prior reviews, primary
      case studies, and randomized controlled trials of infant and pediatric MT.
      Current findings provide varying levels of evidence for the benefits of pediatric
      MT in children who have diverse medical conditions; however, anxiety reduction
      has shown the strongest effect. Future studies should use rigorous study design
      and methodology, with long-term follow-up, for examining the longitudinal effects
      of pediatric MT.

PMID- 18061790
TI  - Complementary and alternative therapies in pediatric oncology.
AB  - Evidence on the science of complementary and alternative medicine (CAM) in
      children with cancer is slowly evolving. Most parents of children with cancer
      want their children to receive state-of-the-art therapy, which generally includes
      chemotherapy, radiation, and surgery. Increasingly, they also want the
      concomitant use of CAM therapies to help effect a cure or to alleviate symptoms.
      The ideal model of integrative pediatric oncology offers safe and effective CAM
      therapies in a pediatric hospital or medical center setting which participates in
      the clinical trials network of a pediatric oncology cooperative group setting.

PMID- 18061791
TI  - New clinical and ultrastructural findings in hydroxychloroquine-induced
      cardiomyopathy--a report of 2 cases.
AB  - Hydroxychloroquine- or chloroquine -induced cardiomyopathy is a rare but
      potentially fatal condition. Hydroxychloroquine and chloroquine are often used
      for long-term treatment of rheumatic diseases and for malaria prophylaxis.
      Hydroxychloroquine- and chloroquine-induced cardiomyopathy have well-described
      microscopic features, with the classic electron microscopic findings of myelin
      figures (myeloid bodies). We report on 2 new cases with novel findings. The first
      case, in a patient with systemic lupus erythematosus, was found to have
      megamitochondria in addition to myelin figures seen by electron microscopy. The
      second report describes the first case of hydroxychloroquine cardiomyopathy
      described in a patient with scleroderma. These novel findings will add to the
      present knowledge of hydroxychloroquine-induced cardiomyopathy in its pathology
      and its implication for treatment of rheumatic diseases.

PMID- 18061792
TI  - Coronary artery bypass grafting for Fabry's disease: veins more suitable than
      arteries?
AB  - Coronary artery bypass grafting was performed in a 54-year-old man affected by
      untreated Fabry's disease. Left internal mammary artery (LIMA) and saphenous vein
      grafts were implanted. Surgical samples of LIMA revealed diffuse
      glycosphyngolipid infiltration of smooth muscle cells, whereas SV was normal.
      After surgery, the patient received antithrombotic and enzyme replacement
      therapy. At 1-year follow-up, LIMA graft occluded, whereas saphenous vein graft
      remained patent. In Fabry's disease, veins, probably because of a low pressure
      load, seem to be spared from glycosphingolipid accumulation and are more suitable
      than arteries for grafting. A preventive histology of conduits is suggested
      before graft selection.

PMID- 18061796
TI  - Bariatric surgery and work-up of the massive weight loss patient.
AB  - Bariatric surgery remains the treatment of choice for the extremely obese
      patient, with an exponential growth in the number of procedures performed in
      response to the obesity epidemic. There are a variety of bariatric procedures
      available, which differ according to the method in which they achieve sustained
      weight loss. Plastic surgeons are beginning to see large numbers of patients who
      have undergone bariatric surgery and who have sustained massive weight loss (MWL)
      for evaluation of complex and lengthy-body contouring procedures. Proper
      evaluation of the patient who has sustained MWL requires an understanding of the
      physiologic impact of different bariatric procedures with particular knowledge of
      potential long-term nutritional complications.

PMID- 18061795
TI  - Psychiatric considerations of the massive weight loss patient.
AB  - As bariatric surgery for extreme obesity continues to grow in popularity, so does
      interest in postbariatric surgery body-contouring surgery. There is an extensive
      literature on the psychological characteristics of persons with extreme obesity
      who undergo bariatric surgery and the psychological changes that typically occur
      postoperatively. Far less, however, is known about the psychological aspects of
      body contouring following massive weight loss. This article reviews the
      psychosocial characteristics of individuals with extreme obesity who undergo
      bariatric surgery, as well as the changes in these traits that typically occur
      postoperatively. Because there have been few studies of the psychological aspects
      of patients who have lost massive amounts of weight, we use related literatures
      on the relationship between body image dissatisfaction and other plastic surgical
      procedures to identify the most relevant research and clinical issues for this
      unique patient population. Appropriate psychiatric screening and management of
      these patients is believed to play an important role in successful postoperative
      outcomes.

PMID- 18061797
TI  - Body lift.
AB  - The body in the patient who has lost a massive amount of weight presents an
      extreme form of traditional esthetic and functional body contour concerns.
      Routine body contouring procedures usually produce only suboptimal results in
      this patient population. The body lift described herein is an excellent
      alternative to treat the body contour deformity of the patient who has undergone
      bariatric surgery. As with every technique, careful patient selection, education,
      and preparation are critical to minimizing complications and optimizing outcome.

PMID- 18061798
TI  - Circumferential lower truncal dermatolipectomy.
AB  - Obesity and overweight in the general population have increased significantly
      over the last several years. Such increases have stimulated many approaches to
      treat this condition from a clinical perspective, with improved surgical and
      conservative measures that have become available for controlling overweight. The
      present article examines both established procedures for performing body lift
      procedures and innovative approaches that are now available, as well as their
      potential complications. The problems and solutions discussed in this article
      derive from the authors' own experiences collected over the last 10 years at the
      Department of Plastic and Reconstructive Surgery at the Dreifaltigkeits-Hospital
      in Wesseling, Germany. These surgical procedures are the operations with the
      largest treated body surface area with manageable risks when the planning and
      operation are performed meticulously and conscientiously.

PMID- 18061799
TI  - Gluteal contouring surgery in the massive weight loss patient.
AB  - This article describes some of the salient anatomic issues, a classification
      system, surgical techniques, and a decision-making algorithm available for
      contouring the gluteal region in the patient who has sustained massive weight
      loss (MWL). The gluteal deformities encountered in patients who have lost a
      massive amount of weight are unprecedented in body-contouring surgery, and
      plastic surgeons need uncommon techniques when contouring and augmenting the
      gluteal region in these patients. A better understanding of the anatomy and a new
      surgical armamentarium can improve the cosmetic results of gluteal contouring,
      and, thereby, enhance patient satisfaction in this challenging population.

PMID- 18061801
TI  - Lipoabdominoplasty.
AB  - This article describes extensive liposuction with minimal abdominoplasty, a
      technique developed by the author and colleagues at the Institut Vila-Rovira. The
      technique represents another step in the evolution of liposuction procedures.
      Especially for patients with a body mass index of 30 to 35, the procedure is a
      surgical alternative that preserves the safety of the traditional
      lipoabdominoplasties.

PMID- 18061803
TI  - Upper body lift.
AB  - An upper body lift is needed whenever a massive weight loss patient presents with
      a "dropped out" lateral inframammary crease. It is a combination of a
      brachioplasty, upper-back resection, and breast reconstruction. The operation is
      designed to reverse the particular deformity a patient presents with. This
      article describes three patterns of resection, one for males and two for females.

PMID- 18061804
TI  - Lateral thoracic excisions in the post massive weight loss patient.
AB  - The lateral vertical thoracic excision has been a useful adjunct to more
      traditional techniques. As more patients undergo massive weight loss, more
      patients will present to plastic surgeons with complaints of fullness and excess
      in areas of the body not addressed by more traditional techniques. The lateral
      vertical thoracic excision can offer a solution to a difficult problem.

PMID- 18061806
TI  - Mastopexy after massive weight loss: dermal suspension and selective auto
      augmentation.
AB  - The technique that we outline is extremely versatile for restoring an aesthetic
      and youthful breast shape in the patient who has lost a massive amount of weight.
      Overall, complication rates have been low. Despite the disadvantages of a lengthy
      scar and the need for extensive intraoperative tailoring (which may increase
      operative time), this operation carries an extremely high rate of patient
      satisfaction.

PMID- 18061807
TI  - L brachioplasty correction of excess tissue of the upper arm, axilla, and lateral
      chest.
AB  - Following massive weight loss, patients evolve severe arm deformity, extending
      through the axilla and on to the chest. The L brachioplasty was developed to
      treat the entire deformity through the excision of two unequal ellipses at right
      angles in the form of an "L." More than 50 patients have been treated since 2002
      with esthetic reshaping of the upper arm, leaving inconspicuous scars and only
      minor complications. There have been eight scar revisions, including two Z
      plasties for contracture. The rationale and results compare favorably with
      contemporary techniques. L brachioplasty is our procedure of choice for the
      patient who has had massive weight loss, and it can be applied selectively to the
      aging arm.

PMID- 18061808
TI  - Brachioplasty in the massive weight loss patient.
AB  - The arm deformity encountered in most patients who have had massive weight loss
      is severe. The excess crosses the axilla as an extension of the posterior
      axillary fold. Surgical treatment requires crossing the axilla with the excision.
      The authors describe a surgical technique that they have found to be powerful and
      effective. The position of the final scar is on the posterior aspect of the arm
      and is more hidden when the person is animating.

PMID- 18061810
TI  - Current concepts in medial thighplasty.
AB  - Lockwood's changes in surgical design of the medial thigh lift have improved
      results and decreased complications but still have the fundamental problem of
      poor tissue fixation to rigid tissue. To provide increased support to the medial
      thigh incisions, modifications to this technique have been tried. This article
      describes the authors' approach to the medial thigh lift in both those patients
      who have undergone traditional weight loss and the massive weight-loss thigh-lift
      patient.

PMID- 18061811
TI  - Thigh reduction in the massive weight loss patient.
AB  - With the variety of bariatric procedures available today, there is a steadily
      growing stream of massive weight loss patients. Although there have been major
      advances in upper extremity and upper and lower truncal contouring, the lower
      extremity often remains the most difficult to treat. Historically, thigh
      reductions were designed to treat minor medial thigh laxity. The technique
      described in this article is specifically designed for the massive weight loss
      patient who presents with extensive thigh deformity. For lesser deformities more
      traditional techniques should be used.

PMID- 18061812
TI  - Safety first: precautions for the massive weight loss patient.
AB  - A significant increase in bariatric procedures has led to success in maintaining
      long-term weight loss. The increasing population of patients who have lost
      massive amounts of weight also has led to a growing responsibility placed on body
      contouring surgeons to perform safe and cautious procedures in this inherently
      difficult patient population. We stratify risk groups and present several case
      reports and a systematic review of safety precautions. The risks and
      complications of body contouring can be minimized by a team approach with a
      meticulous attention to patient evaluation, preoperative planning, safe detailed
      operative measures, and thorough postoperative care.

PMID- 18061814
TI  - Lifestyle interventions.
AB  - Lifestyle intervention for the self-management of diabetes is complex and will
      constantly evolve as the patient's life changes and the diabetes progresses.
      Although the patient ultimately makes the most important decisions with regard to
      self-management, the primary care provider plays a critical role as expert
      consultant to the patient in this effort. Involving a multidisciplinary team in
      the care and education of the patient with diabetes is an effective approach that
      capitalizes on each profession's expertise. The team must work collaboratively to
      ensure that patients are provided the educational underpinnings and taught the
      behavior change skills that will empower them to effectively master their
      diabetes.

PMID- 18061815
TI  - Management of mental illness in patients with diabetes.
AB  - Patients who have diabetes commonly have mood, anxiety, and psychotic disorders.
      These disorders may have multiple biologic underpinnings. Without treatment, care
      becomes complicated and outcomes are poor. Early diagnosis and biopsychosocial
      treatment that integrates medical and psychiatric interventions is highly
      desirable. Medications have a major role in treatment, although caution must be
      exercised because of potential side effects. Psychiatric consultation or
      management may be required for urgent or severe cases. An appreciation of
      culture, both ethnic and beyond, is a foundation for enhancing physician-patient
      relations and developing realistic expectations for treatment.

PMID- 18061816
TI  - Diagnosis and management of type 2 diabetes and prediabetes.
AB  - Treatment of type 2 diabetes mellitus (T2DM), a progressive disease, requires
      early and appropriate therapies, with frequent monitoring and reassessment to
      make certain goals are attained. Chronic hyperglycemia can cause macrovascular
      and microvascular complications, many of which may be apparent on initial
      diagnosis. As beta-cell function deteriorates and insulin resistance intensifies,
      patients find that oral pharmacologic therapy is becoming less effective at
      minimizing the effects of chronic hyperglycemia. Eventually, most will require
      exogenous insulin therapy. Primary care physicians manage over 90% of T2DM
      patients, so we must have a better understanding of our roles as patient
      educators, advocates, and medical providers, and do everything in our power to
      help our patients achieve the lowest and safest glycated hemoglobin (A1C)
      possible.

PMID- 18061817
TI  - Polycystic ovary syndrome: a common reproductive and metabolic disorder
      necessitating early recognition and treatment.
AB  - Patients who have polycystic ovary syndrome (PCOS) present with infertility,
      recurrent miscarriages, menstrual irregularities, hirsutism, and acne. Many also
      have metabolic and hormonal abnormalities that can significantly increase risk
      for coronary artery disease, type 2 diabetes mellitus, and endometrial carcinoma.
      PCOS patients should be screened for obstructive sleep apnea. Early recognition
      may reverse physical signs of the disease, while correcting the metabolic
      abnormalities that can pose significant health risk if untreated. Although
      lifestyle modification and pharmacotherapy are used to treat PCOS, there are few
      long-term outcome data regarding benefits of metabolic interventional strategies.
      Insulin sensitizers can improve ovulatory function, lower insulin resistance,
      lower androgen levels, and increase the likelihood of becoming pregnant. Further
      studies should yield other treatment options.

PMID- 18061818
TI  - Management of type 1 diabetes.
AB  - Although less prevalent than type 2 diabetes, autoimmune type 1 diabetes presents
      numerous challenges, including many that must be addressed daily. Patients must
      have appropriate tools to confront and manage their physiologic insulin
      deficiency syndrome. The vast majority of patients who have type 1 diabetes
      require a basal insulin to suppress hepatic glucose production in the fasting
      state, as well as prandial (mealtime) insulin to cover glycemic excursions that
      occur as carbohydrate absorption occurs in response to meals. Patients need
      algorithms to self-adjust both their prandial and basal insulin doses. The
      ultimate goal of all patients who have diabetes is to attain and maintain an A1C
      as close to normal as possible, while maintaining safety, avoiding hypoglycemia,
      and minimizing glycemic variability, as close to normal as possible, while
      maintaining safety and avoiding severe hypoglycemia.

PMID- 18061819
TI  - Management of diabetes in pregnancy, childhood, and adolescence.
AB  - Primary care physicians are likely to become involved with the management of many
      types of patients who have diabetes, including children and adolescents. Although
      specialty consultation is necessary for these young patients, the primary care
      physician often provides a strong cornerstone of therapy revolving around
      complication surveillance, disease prevention (especially in patients who have
      gestational diabetes following the completion of their pregnancy), motivation
      toward making healthy lifestyle choices, and support of the family unit once a
      new diagnosis of type 1 diabetes mellitus is made. By promoting a healthy
      lifestyle to high-risk patients, primary care physicians can help delay the onset
      and reduce the incidence of type 2 diabetes in children and adolescents.

PMID- 18061820
TI  - Insulin pump therapy (continuous subcutaneous insulin infusion).
AB  - Continuous subcutaneous insulin infusion has provided patients who have diabetes
      with a system for achieving treatment targets with a lower incidence of severe
      hypoglycemia. Patients prefer the flexibility, convenience, and physiologic
      glycemic control of continuous subcutaneous insulin infusion. Future insulin
      pumps will be implanted within the body and the "loop" will be closed, providing
      a physiologic insulin delivery system. This system will provide the means for
      achieving near-normal glycemia, limit episodes of severe hypoglycemia, and
      prevent long-term complications of diabetes mellitus.

PMID- 18061821
TI  - Office-based screening, prevention, and management of diabetic foot disorders.
AB  - Diabetic foot problems are significant cause of morbidity. With good medical
      care, the progression of neuropathy and vascular disease can be slowed but not
      stopped. Effective diabetic foot care requires screening to detect the at-risk
      foot, prevention to avoid the occurrence of ulcers, and treatment to heal ulcers
      quickly before they become more significant problems. Screening comprises
      assessment of patient behaviors and skin, neurologic, and vascular examinations.
      Prevention is accomplished by patient education and appropriate footwear or
      bracing. Recognition of Charcot's arthropathy can greatly reduce the risk of
      later problems. If problems progress beyond the scope of basic treatment by the
      primary care physician, referral to other members of the diabetic team is
      indicated.

PMID- 18061822
TI  - Recognition and management of diabetic neuropathy.
AB  - Pain and disability associated with diabetic neuropathy have economic, social,
      and emotional consequences. Because these complications impact patients during
      the prime of their lives, physicians should screen and manage patients at risk.
      Improvement in glycemic and lipid management, glycemic variability, and lifestyle
      interventions such as smoking cessation should limit disease progression.
      Patients who have symptomatic disease should be treated, targeting a 50%
      improvement in pain within 4 weeks. Physicians should also strive to improve
      function and comorbidities such as sleep disorders, depression, and anxiety.
      Patient education is critical for treatment adherence and prevention of serious
      complications. Consequences associated with diabetic neuropathy include
      nontraumatic amputations and silent ischemia; thus proper foot care and education
      regarding "warning signs" of silent ischemia are necessary.

PMID- 18061824
TI  - Complications in primary and secondary acquired cholesteatoma: a prospective
      comparative study of 62 ears.
AB  - OBJECTIVES: This study aimed to compare the clinicopathologic behavior of
      complications in primary and secondary acquired cholesteatoma and figure out the
      differences between them. DESIGN: This was a prospective cross-sectional study.
      METHODS: This was a study conducted in a tertiary referral medical college
      hospital comprising of 62 ears, of which 32 were in the primary acquired
      cholesteatoma group (PACG) and 30 were in the secondary acquired cholesteatoma
      group (SACG). We compared the 2 groups with respect to 7 prognostic variables, as
      follows: age distribution, sex, duration of ear discharge, pathology in the ear,
      predisposing disease focus in nose and throat, pattern of complications, and
      microbiology of ear. OBSERVATION AND RESULTS: The presence of cholesteatoma
      increased the risk for complications by more than 2 times in PACG, but the
      presence of granulation tissue did not show the same risk. More than half of the
      ears with complication contained some or the other predisposing disease focus in
      the nose or throat. The PACG was 3 times more prone to complications than the
      SACG in the presence of these foci. They showed a similar pattern of
      complications. Brain abscess and mastoid infections were the commonest
      complications. CONCLUSIONS: The PACG was more prone to complications than the
      SACG in the presence of cholesteatoma and focus in the nose and throat.
      Irrespective of the different pathologic origin of the 2 types, the patterns of
      complications remained the same with no major differences, indicating a common
      final pathway in the natural course of the disease.

PMID- 18061825
TI  - Long-term results of different treatment modalities for glottic insufficiency.
AB  - PURPOSE: The purpose of this study was to investigate the early and long-term
      functional results of thyroplasty type-I and injection laryngoplasty using fat or
      calcium hydroxylapatite. MATERIALS AND METHODS: Thirty patients with glottic
      insufficiency were included and followed up between 1-7 years. Patients with
      glottic bowing or sulcus vocalis were selected for injection augmentation of the
      vocal folds, while those with unilateral vocal fold immobility underwent
      medialization thyroplasty. Perceptual and acoustic analysis of voice, and
      videolaryngostroboscopy were performed before and after surgery. RESULTS: After
      the surgery, GRBAS scale of all patients demonstrated significant change in grade
      of severity, roughness, and breathiness. Acoustic analysis demonstrated
      significant change in Fo, jitter, shimmer, noise to harmonic ratio, and maximum
      phonation time (MPT) in thyroplasty group, while those demonstrated significant
      change in Fo (lowest) and jitter, and MPT in injection augmentation group.
      CONCLUSIONS: Medialization thyroplasty is the gold standard for the management of
      glottic insufficiency, regardless of the severity of glottic gap. However,
      injection augmentation of the vocal folds may be considered as an alternative in
      the treatment of patients with small glottic gap. Further studies with larger
      groups and long follow-up periods are required to figure out the proper material
      for injection laryngoplasty.

PMID- 18061826
TI  - Frequency of esophageal stenosis after simultaneous modulated accelerated
      radiation therapy and chemotherapy for head and neck cancer.
AB  - BACKGROUND: Chronic esophageal toxicity after radiotherapy alone for cancer of
      the head and neck (HNCa) is rare: 2.6% for strictures and 0.8% for stenosis after
      a 60-Gy dose. With combined modality therapy, stricture rates of 22% to 37% have
      been reported. We report the frequency of esophageal toxicity after simultaneous
      modulated accelerated radiation therapy (SMART) with chemotherapy for HNCa.
      METHODS: The records of the otolaryngology/head and neck surgery department of
      Emory University, Atlanta, GA, were screened for patients undergoing combined
      modality therapy using SMART for HNCa. Radiation Oncology records were reviewed
      for target and critical normal structure dosimetry, with detailed analysis of
      esophageal and supraglottic laryngeal dosimetry. Hospital and clinic records were
      reviewed for evidence of esophageal toxicity. RESULTS: From January 2003 to
      August 2005, 99 patients underwent definitive therapy for squamous cell HNCa
      using SMART and chemotherapy. Follow-up was documented in all cases. Median dose
      to sites of gross primary or nodal disease was 70.29 Gy, at 2.13 Gy per fraction.
      Median dose to the ipsilateral neck was 63.03 Gy at 1.91 Gy per fraction. Median
      dose to the contralateral neck in 97 patients treated was 57.75 Gy at 1.75 Gy per
      fraction. Thirteen (13%) patients developed esophageal strictures. Five (5%)
      patients had complete esophageal stenosis. Four (14%) of the 29 patients with
      either a hypopharyngeal primary or a N2c nodal disease developed complete
      stenosis. A statistically larger esophageal volume of esophagus reactivity > or =
      60 Gy (V(60)) was found in patients who developed stenosis/stricture when
      compared with a randomly selected population of N2a/b patients who did not
      develop those toxicities. Esophageal stenosis/stricture was also numerically more
      common in patients receiving taxane-based chemotherapy, developing in 23%, as
      opposed to 9% in patients treated with platinum-based chemotherapy. CONCLUSION:
      The risk of esophageal stenosis may increase with SMART and chemotherapy for
      HNCa. Potential mechanisms to reduce this include (a) contouring the esophagus as
      a dose-limiting structure; (b) early flexible examination posttreatment, with
      early intervention with dilation; (c) improved therapy for mucositis.

PMID- 18061827
TI  - Expression of histamine receptors (H(1), H(2), and H(3)) in the rabbit
      endolymphatic sac: an immunohistochemical study.
AB  - OBJECTIVE: The endolymphatic sac (ES) is part of the membranous labyrinth of the
      inner ear. Its central role in immunologic activity within the inner ear has been
      confirmed by numerous studies. The aim of this study was to investigate the
      expression of histamine receptors (H(1), H(2), H(3)) in the rabbit ES. METHODS: A
      total of 10 healthy male New Zealand white rabbits weighing 2 to 3 kg were used
      in the experiments. For immunohistochemical studies, immunostaining was performed
      according to the avidin-biotin-peroxidase complex technique. RESULTS: Serial
      sections of the ES of rabbits revealed the presence of H(1), H(2), and H(3)
      receptor immunoreactivity. Immunoreactive cells for all H(1), H(2), and H(3) were
      found in the epithelial and subepithelial layers of the duct and the proximal ES.
      In conclusion, this study showed the immunohistochemical localization of H(1),
      H(2), and H(3) receptors in the ES of rabbits. These receptors may be important
      in the homeostasis of the inner ear. In addition, they may be target receptors in
      the medical treatment of inner ear disorders such as endolymphatic hydrops.

PMID- 18061828
TI  - Combination antifungal therapy for invasive aspergillosis: can it replace high
      risk surgery at the skull base?
AB  - OBJECTIVE: The increasing volume of literature on Aspergillus sinus infection is
      confusing because different authors stress different aspects of the disease. It
      is generally accepted that standard therapy consists of surgical debridement and
      medication with systemic amphotericin B. Patients who fail the standard therapy
      or those who cannot tolerate amphotericin B pose a dilemma. This study attempted
      to address the issues concerning combination therapy in invasive aspergillosis.
      MATERIALS AND METHODS: We conducted a prospective randomized study on 6
      apparently immunocompetent patients with invasive aspergillosis complicated by
      orbital and intracranial spread. All the patients were treated with a combination
      of amphotericin B (2.5 g) and itraconazole (6 months). They were monitored
      clinically and radiologically before, during, and after their combined antifungal
      therapy management. RESULTS: Among the 6 immunocompetent patients, orbital
      involvement was seen in 5, skull base erosion with intracranial extension was
      seen in 2, and infratemporal fossa extension was seen in 2. After completion of
      treatment with 1.5 g of amphotericin, the paranasal sinus part of the lesion
      disappeared. However, there was residual lesion in the intracranial part that
      completely disappeared only after treatment with 2.5 g of amphotericin and 6
      months of itraconazole therapy. CONCLUSIONS: Invasive aspergillosis has been
      increasingly reported among immunocompetent patients. No single surgical or
      medical maneuver, including orbital exenteration, guarantees cure. The
      combination of amphotericin B and itraconazole for skull base aspergillosis
      represents a real step forward in the treatment of invasive aspergillosis.

PMID- 18061829
TI  - Traumatic ossicular dislocations: etiology and management.
AB  - OBJECTIVE: This study was conducted to discuss the etiologic factors, clinical
      radiologic findings, and surgical outcomes in patients with traumatic ossicular
      pathology. MATERIAL AND METHODS: Thirty-two patients with conductive hearing loss
      due to trauma were retrospectively analyzed. Their mean age was 24.56 +/- 7
      years. The average delay from injury until treatment was 5.7 years. Air and bone
      conduction hearing thresholds were measured by pure tone audiometry on initial
      admission, at 1 month postoperatively and during follow-up at 6-month intervals.
      Mean follow-up time is 3.2 years. The hearing threshold was calculated as the
      mean value of the threshold for 500, 1000, 2000, and 3000 Hertz. All patients
      were evaluated by high-resolution computerized tomography of the temporal bone at
      axial and coronal sections before the surgery. RESULTS: Traffic accident was the
      common cause of injury. Seven patients had temporal bone fracture. Six patients
      had facial paralysis ranging between House-Brackmann grades II and IV.
      Incudostapedial disarticulation was the most common ossicular pathology. Closure
      of air-bone gap within 10 and 20 decibels was observed in 37.6% and 71.9% of the
      patients, respectively. There is an improvement of 10 decibels or more in the
      hearing threshold of 27 (84.3%) patients. CONCLUSIONS: Head trauma can be
      associated with ossicular disruption, which should be suspected in patients with
      conductive hearing loss that persists after a healing process of 2 months. The
      diagnosis can be best confirmed by tomography. Hearing results after immediate or
      delayed ossiculoplasty are apparently satisfying, although late cases are assumed
      to be associated with adhesion or fibrosis.

PMID- 18061830
TI  - Evaluation of nasal symptoms and mucociliary function in patients with allergic
      rhinitis treated with chemosurgery using trichloroacetic acid.
AB  - PURPOSE: We treated allergic rhinitis with trichloroacetic acid (TCA) applied to
      the inferior turbinates. Further clinical evaluations were made to determine the
      effect of TCA application on symptoms of allergic rhinitis. We also report the
      results of measurement of the mucociliary transit time (saccharin time) and nasal
      airway resistance. MATERIALS AND METHODS: A group of 54 patients with perennial
      allergic rhinitis was treated with 80% TCA applied to the inferior turbinate.
      Further clinical evaluations were made to determine the effect of TCA application
      on symptom scores of allergic rhinitis. We also report the results of measurement
      of the mucociliary transit time (saccharin time) and nasal airway resistance in
      those cases. RESULTS: The most common complaint, nasal obstruction, improved
      effectively in 82% of cases, watery rhinorrhea in 86%, and sneezing in 86%, 1
      year after treatment. A significant decrease in scoring was noted for subjective
      nasal obstruction, watery rhinorrhea, and sneezing. Nasal airway resistance was
      effectively reduced 1 year after treatment, and the difference was statically
      significant. In our study, saccharin time appeared to be shortened in the early
      and late periods after the TCA application. There was a statistical difference
      between the before- and after-treatment groups. CONCLUSIONS: We concluded that
      TCA treatment was quite effective for controlling nasal allergic symptoms and
      that it does not damage the mucociliary function.

PMID- 18061831
TI  - Anatomy and anthropometry of human stapes.
AB  - Twelve human stapes from temporal bones fixed by formalin were extracted.
      Different dimensions were measured by an electronic microscope with an accuracy
      of microm. These dimensions were as follows: (1) maximum diameter of stapes head
      parallel to the axis of footplate, 1088 microm (range, 857-1277 microm); (2)
      distance of main nutritional foramen to head surface, 398 microm (range, 250-833
      microm); (3) stapes head to shoulders, 757 microm (range, 571-1000 microm), head
      to foramen, 1047 microm (range, 785-1500 microm), and head to lateral surface of
      footplate, 2612 microm (range, 1892-3400 microm); (4) anterior crus width at
      shoulder, 398 microm (range, 333-500 microm); minimum width of anterior crus, 251
      microm (range, 214-350 microm); (5) posterior crus width at shoulders, 386 microm
      (range, 285-600 microm); minimum width of posterior crus, 191 microm (range, 142
      300 microm); (6) maximum width of footplate near anterior crus, 371 microm
      (range, 321-500 microm), maximum width of footplate near the posterior crus, 411
      microm (range, 357-611 microm), minimum width of footplate, 228 microm (range,
      178-388 microm); (7) maximum width of ossicle, 2298 microm (range, 1928-3050
      microm); (8) angle between crura, 19.5 degrees (range, 15-24 degrees ); and (9)
      diameter of foramen at the end of curve, 1343 microm (range, 1071-1888 microm).

PMID- 18061832
TI  - Endonasal transsphenoidal pituitary surgery: is tumor volume a key factor in
      determining outcome?
AB  - PURPOSE: This study was conducted to evaluate the role of tumor volume in
      excision of pituitary adenomas. MATERIALS AND METHODS: A total of 20 patients
      with pituitary adenoma underwent surgical excision of the tumor by endonasal
      transsphenoidal approach. RESULTS: A preoperative tumor volume of more than 5 mL
      is associated with a 90.90% probability of residual tumor (P < .05, statistically
      significant). CONCLUSION: Tumor volume as a predicting factor for the surgical
      outcome is an evolving concept. Other factors determining the efficacy of tumor
      removal are parasellar and suprasellar extension.

PMID- 18061833
TI  - Objective method for facial motricity grading in healthy individuals and in
      patients with unilateral peripheral facial palsy.
AB  - PURPOSES: This study aimed (a) to associate the House and Brackmann grading
      system with a method of photographic evaluation and distance measuring between
      predetermined facial points, (b) to evaluate the objectivity of the method
      presented, and (c) to establish the grading pattern values for this method and
      their corresponding degrees in the House and Brackmann grading system. METHODS:
      This study presents a method for determining distances on each side of the face
      (eyebrow position and horizontal and vertical positions of mouth angle) related
      to 2 reference lines drawn from the internal ocular angles in photographs of 5
      different facial expressions (at rest, eyes closed, eyebrows raised, smiling, and
      whistling) of 49 individuals with facial function from normal to total unilateral
      peripheral facial palsy. RESULTS: With this, an overall percentage of facial
      asymmetry was established. CONCLUSIONS: 1) It was possible to establish a
      correlation between the House and Brackmann grading system and a photographic
      evaluation method with measuring and comparative analysis of distances between
      predetermined facial points. 2) The method presented is objective. 3) Six
      percentages were established, which correlate to the 6 degrees of the House and
      Brackmann grading system. 4) The presented objective method is useful for
      documentation and following up of patients with peripheral facial palsy,
      particularly in university or medical training research studies.

PMID- 18061834
TI  - The presenting features of middle ear facial nerve sheath tumors: a clinical
      review.
AB  - Facial nerve sheath tumors are the most common middle ear benign neoplasms. Four
      facial nerve sheath tumors in the middle ear were diagnosed in our department
      over a 12-year period, and we described our experience in the management of these
      tumors. A thorough review of the English literature on middle ear peripheral
      nerve sheath tumors has been conducted, and the findings of this review are
      presented and discussed. We have paid particular attention to the presenting
      features of these tumors with the aim of enhancing diagnostic ability.

PMID- 18061835
TI  - Unintended benefits of immunosupression on autoimmune disease due to
      chemoradiation therapy for head and neck cancer.
AB  - The immune system is an important factor in the host's defenses against cancer.
      Immunosupression by radiation and/or chemotherapy is often associated with
      systemic and hematologic complications, opportunistic infections, and the
      development of malignancies, but immunosupression can also have beneficial
      effects, which are sometimes incidental. We report 2 patients with autoimmune
      diseases where immunosupression had beneficial effects. The first case is about a
      patient with carcinoma of the tonsil, with severe rheumatoid arthritis, who was
      treated with chemoradiation, which resulted in remission of his arthritis. The
      second case is about a patient with severe atopic eczema who was on long-term
      treatment with psoralen and ultraviolet A radiation and azathioprine; the patient
      developed metastatic carcinoma of the lip, which was treated with surgery and
      radiation that resulted in complete remission of his eczema.

PMID- 18061836
TI  - Endoscopic removal of an unusual foreign body in the nasopharynx of an adult.
AB  - We report a rare case of sewing needle impaction in the nasopharynx of an adult
      patient after sneezing. The impacted foreign body was removed using nasal
      endoscope. To the authors' knowledge, such a case has not been previously
      reported in medical literature.

PMID- 18061837
TI  - Verrucous carcinoma of the temporal bone.
AB  - Verrucous carcinoma is a highly differentiated variant of squamous cell
      carcinoma. In the literature, 11 cases of primary verrucous carcinoma of the
      temporal bone have been reported. We present a 48-year-old woman who had
      undergone radical mastoidectomy because of chronic otitis media 20 years ago;
      consequently, verrucous carcinoma occurred in the mastoid cavity. We discuss
      verrucous carcinoma of the temporal bone with the review of literature.

PMID- 18061838
TI  - Melioidosis: an uncommon cause of neck abscess.
AB  - INTRODUCTION: Melioidosis is a life-threatening disease caused by B.
      pseudomallei. It is endemic in Southeast Asia with a few reports from the Western
      world. It is transmitted via inhalation, ingestion or direct contact with an open
      wound. Clinically it may present with local or systemic symptoms. Mortality rate
      is very high in systemic disease; but local infection is usually mild, which
      causes delay in seeking medical attention. CASE REPORT: We report a case of neck
      melioidosis presenting as a parapharyngeal abscess that was successfully managed
      with incision and drainage and intravenous ceftazidime and co-trimoxazole for 6
      weeks followed by eradication therapy with oral co amoxiclav. CONCLUSION: Neck
      melioidosis must be considered one of differential diagnoses for "cold abscesses"
      of the neck, especially in an endemic area, in Asian migrants, or in those with
      history of previous visit from the endemic regions.

PMID- 18061839
TI  - Proteomics and the kidney: an evolution.

PMID- 18061840
TI  - Use of quantitative mass spectrometry analysis in kidney research.
AB  - An important component of nephrology research is the discovery of novel proteins
      that control cellular and molecular events that contribute to normal kidney cell
      biology and disease. Identifying perturbation of normal cellular protein
      expression and interactions within signaling networks is critical for
      understanding these regulatory events. Methods that couple 2-dimensional
      capillary liquid chromatography and tandem mass spectrometry (2D-LC-MS/MS)
      analysis have greatly facilitated this discovery science. Coupling 2D-LC-MS/MS
      analysis with automated genome-assisted spectra interpretation allows a direct,
      high-throughput, and high-sensitivity identification of hundreds to thousands of
      individual proteins from targeted complex biological samples. The systematic
      qualitative and quantitative comparison of experimental/disease conditions and
      appropriate controls allow protein function or disease states to be modeled. This
      review discusses the different purification and quantitative strategies that have
      been developed and used in combination with 2D-LC-MS/MS and computational
      analysis to define regulatory events in kidney biology and disease.

PMID- 18061841
TI  - Proteomic methods for biomarker discovery in urine.
AB  - Many challenges exist with disease-state biomarker identification. These
      challenges include sample heterogeneity, poorly designed sample sets,
      insufficient numbers of samples, as well as inconvenient workflows, inadequate
      methodology, and development of false-positive markers resulting from protein
      degradation during sample handling. Yet despite these difficulties, substantial
      progress has been achieved with the application of proteomic methods toward
      biomarker discovery in renal disease. Significant advances have occurred in the
      past decade with electrophoretic, chromatographic, and mass spectrometric methods
      for discerning biomarkers of disease. Recent applications of proteomics to the
      study of renal disease have identified new mechanisms in renal disease
      progression and established protein expression profiles for complex renal
      diseases including glomerular and tubular pathologies. In some cases these
      protein profiles have proven successful with guiding patient treatment and
      markers for pharmacologic therapies. Proteomic analysis only recently has been
      applied to the study of renal disease, yet it has shown substantial potential for
      future successes.

PMID- 18061842
TI  - Direct tissue analysis by matrix-assisted laser desorption ionization mass
      spectrometry: application to kidney biology.
AB  - Direct tissue analysis using matrix-assisted laser desorption ionization mass
      spectrometry (MALDI MS) provides in situ molecular analysis of a wide variety of
      biological molecules including xenobiotics. This technology allows measurement of
      these species in their native biological environment without the use of target
      specific reagents such as antibodies. It can be used to profile discrete cellular
      regions and obtain region-specific images, providing information on the relative
      abundance and spatial distribution of proteins, peptides, lipids, and drugs. In
      this article, we report the sample preparation, MS data acquisition and analysis,
      and protein identification methodologies used in our laboratory for
      profiling/imaging MS and how this has been applied to kidney disease and
      toxicity.

PMID- 18061843
TI  - Metabolomics as an extension of proteomic analysis: study of acute kidney injury.
AB  - Although proteomics studies the global expression of proteins, metabolomics
      characterizes and quantifies their end products: the metabolites, produced by an
      organism under a certain set of conditions. From this perspective it is apparent
      that proteomics and metabolomics are complementary and when joined allow a fuller
      appreciation of an organism's phenotype. Our studies using (1)H-nuclear magnetic
      resonance spectroscopic analysis showed the presence of glucose, amino acids, and
      trichloroacetic acid cycle metabolites in the urine after 48 hours of cisplatin
      administration. These metabolic alterations precede changes in serum creatinine.
      Biochemical studies confirmed the presence of glucosuria, but also showed the
      accumulation of nonesterified fatty acids, and triglycerides in serum, urine, and
      kidney tissue, despite increased levels of plasma insulin. These metabolic
      alterations were ameliorated by the use of fibrates. We propose that the injury
      induced metabolic profile may be used as a biomarker of cisplatin-induced
      nephrotoxicity. These studies serve to illustrate that metabolomic studies add
      insight into pathophysiology not provided by proteomic analysis alone.

PMID- 18061845
TI  - Proteomics and diabetic nephropathy.
AB  - Proteomic methods have found broad applications in kidney disease research and
      more specifically in diabetic nephropathy (DN) research. Proteomic methods such
      as 2-dimensional gel electrophoresis have been used to gain insight into
      glomerular and tubular nephropathies including DN. At the protein level,
      differences in high-abundant proteins in DN have been shown to reflect primarily
      differentially posttranslationally modified plasma proteins. Higher-sensitivity
      proteomic methods (eg, liquid chromatography-mass spectrometry) have pushed the
      boundaries on the known urinary proteome to include more than 1,500 proteins.
      These same high-sensitivity methods have been applied toward profiling urinary
      peptides, which has resulted in methods to diagnostically screen urine to
      differentiate between type-2 diabetes mellitus and type-1 diabetes mellitus
      urine, normal versus microalbuminuria, or by angiotensin II receptor blocker
      treatment. Proteomic methods are being used to show response to insulin gene
      therapy in an animal model or alterations in the renal cortex mitochondrial
      proteome with the development of the diabetic phenotype. Proteomic methods
      continue to aid in the discovery of new mechanisms of diabetic pathology and
      understanding of the etiology of diabetic complications.

PMID- 18061844
TI  - Calorimetric analysis of the plasma proteome.
AB  - The plasma proteome is a complex mixture of more than 3,000 proteins that has
      routinely been exploited by physicians for clinical diagnostic assays. More
      recently, the low-abundance region of the proteome has been examined for
      potential biomarkers of disease. A calorimetric assay has been developed that
      exploits a new physical basis with which to interrogate the plasma proteome. This
      article provides a brief overview of the use of the plasma proteome in clinical
      diagnosis and biomarker discovery and then introduces the new calorimetric assay.
      Some initial results are reported that indicate the potential clinical utility of
      the assay.

PMID- 18061847
TI  - Proteomic analysis in pediatric renal disease.
AB  - Children with renal disease have tremendous potential for recovery, particularly
      when disease processes are detected early in the disease course. However,
      invasive diagnostic maneuvers can be challenging, especially in younger children
      who may require general anesthesia. Urine proteomics technologies present an
      opportunity to discover noninvasive yet informative diagnostic and prognostic
      markers of renal disease in children. In this article we review current concepts
      regarding the normal urine proteome, followed by an overview of urine proteomics
      as applied to nephrotic syndrome, and conclude with a discussion of some of the
      challenges of performing proteomic profiling on nephrotic urine, with its
      inherent abundance of proteins.

PMID- 18061849
TI  - Essentials of equine renal and urinary tract physiology.
AB  - Knowledge of urinary tract anatomy and the numerous functions of the kidney in
      regulating fluids, electrolytes, acid-base balance, and waste products improves
      the ability of the clinician to diagnose, treat, and make appropriate
      recommendations for the management of the horse with renal disease. Several
      conditions can directly or indirectly affect renal function on a temporary or
      permanent basis. Endogenous and exogenous compounds (eg, drugs, toxins,
      hemoglobin) alone or in combination with inappropriate renal blood flow can
      promote or exacerbate renal disease.

PMID- 18061846
TI  - Proteomics for biomarker discovery in acute kidney injury.
AB  - Acute kidney injury (AKI), previously referred to as acute renal failure,
      represents a common and devastating problem in clinical medicine. Despite
      significant improvements in therapeutics, the mortality and morbidity associated
      with AKI remain high. A major reason for this is the lack of early markers for
      AKI, and hence an unacceptable delay in initiating therapy. Fortunately, the
      application of innovative technologies such as functional genomics and proteomics
      to human and animal models of AKI has uncovered several novel biomarkers and
      therapeutic targets. The most promising of these are chronicled in this review.
      These include the identification of biomarker panels in plasma (neutrophil
      gelatinase-associated lipocalin and cystatin C) and urine (neutrophil gelatinase
      associated lipocalin, kidney injury molecule-1, interleukin-18, cystatin C,
      alpha1-microglobulin, Fetuin-A, Gro-alpha, and meprin). It is likely that the AKI
      panels will be useful for timing the initial insult, and assessing the duration
      and severity of AKI. It is also probable that the AKI panels will distinguish
      between the various etiologies of AKI and predict clinical outcomes. It will be
      important in future studies to validate the sensitivity and specificity of these
      biomarker panels in clinical samples from large cohorts and from multiple
      clinical situations. Such studies will be facilitated markedly by the development
      of commercial tools for the reproducible measurement of biomarkers across
      different laboratories.

PMID- 18061850
TI  - Examination of the urinary tract in the horse.
AB  - Pathologic conditions of the urinary tract may produce specific clinical signs,
      but they are more than likely to be nonspecific clinical signs, which often occur
      with chronic renal disease in addition to countless other diseases. Further,
      clinical signs that may seem to be directly related to the urinary tract may be
      the result of other systemic diseases. Thus, before embarking on diagnostics, it
      is important to obtain a thorough history and physical examination.

PMID- 18061851
TI  - Acute renal failure in horses.
AB  - Acute renal failure (ARF) in horses is usually prerenal or renal in origin and is
      most often caused by hemodynamic or nephrotoxic insults. The clinical management
      of patients that have ARF is largely supportive, including correction of fluid
      deficits and electrolyte and acid-base disturbances and treatment and reversal of
      the underlying cause. Use of dopamine and mannitol to promote renal blood flow
      and urine output is no longer recommended.

PMID- 18061852
TI  - Chronic renal failure in horses.
AB  - Chronic renal failure is a syndrome of progressive loss of renal function that
      results in loss of urinary concentrating ability, retention of nitrogenous and
      other metabolic end products, alterations in electrolyte and acid-base status,
      and dysfunction of several hormone systems. This article describes the
      prevalence, causes, clinical signs, diagnostic evaluation, and management of
      horses afflicted with chronic renal failure. It is hoped that this article
      illustrates that chronic renal failure, when detected in the earlier stages of
      disease, can be managed successfully in the short-term allowing owners to enjoy a
      period of time of ongoing productivity, performance, or companionship until loss
      of condition reaches the point that euthanasia becomes warranted.

PMID- 18061853
TI  - Equine urolithiasis.
AB  - The prevalence of equine urolithiasis has been estimated to be low. In horses
      with clinical signs of urolithiasis, uroliths are most commonly encountered in
      the urinary bladder, but it is not uncommon to detect uroliths in more than one
      location. The most common clinical signs for cystic calculi are urine scalding of
      the hind limbs, hematuria, tenesmus and dysuria. Numerous surgical techniques and
      approaches have been described for the treatment of urolithiasis in horses;
      however, independent of which approach is chosen, the goal should be to remove
      all calculi completely from the urinary tract, thus decreasing the chance of
      recurrence of urolithiasis. Laser lithotripsy and shock wave lithotripsy
      represent means to fragment uroliths with little morbidity, but limited
      availability of and costs associated with the equipment have precluded these
      technologies from being used more commonly in horses.

PMID- 18061854
TI  - Equine renal tubular disorders.
AB  - Renal tubular disorders have been sporadically reported in horses. Only three
      types of tubular defects have been recognized: (1) nephrogenic diabetes
      insipidus, attributable to unresponsiveness of the renal tubules to antidiuretic
      hormone; (2) distal renal tubular acidosis (RTA; type I); and (3) proximal RTA
      (type II). The following review focuses on RTA and nephrogenic diabetes
      insipidus.

PMID- 18061855
TI  - Polyuria and polydipsia in horses.
AB  - Polyuria and polydipsia provide a diagnostic challenge for the equine clinician.
      This article describes the various known causes of polyuria and polydipsia in
      horses and provides a description of a systematic diagnostic approach for
      assessing horses with polyuria and polydipsia to delineate the underlying cause.
      Treatment and management strategies for addressing polyuria and polydipsia in
      horses are also described.

PMID- 18061856
TI  - Hematuria and pigmenturia of horses.
AB  - Hematuria and pigmenturia of horses are discussed in this article. Equine urine
      is normally straw colored. Discolored urine can be caused by contamination with
      red blood cells, hemoglobin, myoglobin, oxidizing agents normally found in urine,
      and plant-derived pigments.

PMID- 18061857
TI  - Toxins affecting the urinary system.
AB  - Many different substances can induce toxic damage to various structural
      components of the equine kidney, and most lack pathognomonic signs. Some of these
      agents have specific treatments, although many do not. Supportive and symptomatic
      therapy is an important aspect of treatment of most cases of equine
      nephrotoxicosis. Regardless of cause, if the toxic substance is removed or
      neutralized before significant renal damage, full recovery of renal function may
      occur. Many horses already have significant renal damage before a definitive
      diagnosis is made, and the prognosis for full recovery thus remains guarded.

PMID- 18061858
TI  - Congenital anomalies of the equine urinary tract.
AB  - Congenital anomalies of the urinary tract in horses may be difficult to diagnose
      and treat. Presenting complaints are variable and include weight loss,
      depression, dysuria, hematuria, and mild colic. Although the most severe
      abnormalities are diagnosed in the neonate, some diseases, such as ectopic
      ureter(s), may be identified in older horses. In human medicine, the fetus is
      examined in the prenatal period for evidence of urinary tract dysfunction, but
      this is not yet common practice in equine medicine. As a result, urinary tract
      anomalies are diagnosed after birth using a wide variety of diagnostic
      modalities.

PMID- 18061861
TI  - Strengthening gynecologic cancer prevention studies.
AB  - This article describes the elements in the design of cancer-prevention trials and
      the skills needed to evaluate the study outcomes in this field. Efforts to
      prevent gynecologic malignancies face some methodological challenges common to
      other cancer-prevention studies, such as choice of study design, population to be
      studied, and agent to be administered (or intervention to be made). Flaws in
      making these choices or in analyzing results can lead to misattribution of
      effects or cause important findings to be overlooked. In addition, some
      investigators must address issues that have arisen in response to prevention
      trial results from the past decade. Cancer prevention efforts have recently
      suffered some well-publicized and not-so-well publicized setbacks. The prominence
      of some of these findings should not overshadow well-established achievements and
      recent successes.

PMID- 18061862
TI  - Hereditary ovarian cancer--assessing risk and prevention strategies.
AB  - Hereditary ovarian cancers are almost entirely attributable to mutations in
      BRCA1/2 or the genes of DNA mismatch repair. Identifying individuals at risk
      requires a complete family history and evidence-guided genetic testing. Screening
      of women at increased risk for ovarian cancer can be considered in those not
      wishing prophylactic surgery and typically should include a twice-annual pelvic
      examination, serum CA-125 measurement, and transvaginal sonography. Patients must
      understand that these measures have not been conclusively proven to improve early
      detection or long-term survival. In all mutation carriers who have completed or
      do not desire childbearing, prophylactic bilateral salpingo-oophorectomy must be
      strongly considered.

PMID- 18061863
TI  - Strategies for ovarian cancer prevention.
AB  - Women who have documented BRCA1 or BRCA2 mutations have a significantly increased
      lifetime risk of ovarian and breast malignancies. Many women, however, have a
      perceived personal risk of ovarian cancer despite a calculated low risk, and some
      seek ways to reduce the risk for ovarian cancer. Given the low prevalence of
      ovarian cancer in the general population, no screening test has achieved
      satisfactory levels of disease prediction. This article discusses the efficacy of
      available screening modalities and reviews current risk-reduction strategies and
      their effectiveness for preventing ovarian cancer.

PMID- 18061864
TI  - Ovarian cancer hormonal and environmental risk effect.
AB  - To understand the influence of hormonal and environmental factors on the risk of
      ovarian cancer, it is important to remember the established risk factors and
      postulated mechanisms that lead to the development of ovarian cancer. Several
      risk factors have been identified as increasing the risk of epithelial ovarian
      cancer, including low pariety, infertility, early age of menarche, and late age
      of menopause. This article discusses the different hypotheses and focuses on
      hormonal and environmental risk factors, as well the chemoprevention of
      epithelial ovarian cancer.

PMID- 18061865
TI  - Endometrial cancer associated with defective DNA mismatch repair.
AB  - Defective DNA mismatch repair is one of the most common and best-characterized
      genetic defects detected in endometrial cancer. Defective DNA mismatch repair in
      endometrial cancer can be either inherited or acquired (sporadic). This article
      describes the clinical and pathologic significance of acquired and inherited
      defective DNA mismatch repair in endometrial cancer.

PMID- 18061866
TI  - Management of abnormal uterine bleeding and the pathology of endometrial
      hyperplasia.
AB  - There are no screening tests for endometrial carcinoma, and patients typically
      present with abnormal uterine bleeding. This article discusses the
      pathophysiology and clinical work-up of abnormal uterine bleeding, and risk
      factors for endometrial carcinoma. Atypical complex hyperplasia and the more
      recently defined endometrial intraepithelial neoplasia are well recognized as
      precancers. Evolving knowledge of their genetic alterations provides the
      opportunity to develop molecular markers, so that endometrial diseases may be
      diagnosed at the precancerous or early invasive stage. Emerging molecular markers
      also provide the opportunity to develop clinically useful screening tests for the
      most common malignancy of the female genital tract.

PMID- 18061868
TI  - Prophylactic human papillomavirus vaccination: a breakthrough in primary cervical
      cancer prevention.
AB  - Nearly all cervical cancers require human papillomavirus infection (HPV) for
      subsequent carcinogenesis. The identification of this obligate viral etiology, in
      addition to a vast knowledge about the HPV viral life cycle and resultant host
      response, has led to a vaccine approach to cervical cancer prevention. The use of
      prophylactic cancer vaccine as primary prevention holds the most promise for long
      term cancer prevention but raises some important and as yet unanswered questions
      that are addressed in this article.

PMID- 18061867
TI  - Cervical cancer prevention--cervical screening: science in evolution.
AB  - The incidence and mortality of cervical cancer in the United States has declined
      by more than 70% since the 1950s. This decline is attributed mainly to the
      introduction of Papanicolaou's test in the 1940s. Cervical cancer, however,
      remains the second most frequent of all female malignancies worldwide, with 80%
      of the cases occurring in resource-poor countries. This disparity is attributed
      primarily to the lack of screening and treatment of precancerous lesions. This
      article describes the traditional methods of screening for cervical cancer and
      innovative methods that might help overcome financial and cultural barriers to
      more widespread screening.

PMID- 18061869
TI  - Vulvo-vaginal cancers: risks, evaluation, prevention and early detection.
AB  - Vulvar and vaginal cancers are rare and account for approximately 7% of cancers
      of the female reproductive tract. Vulvar and vaginal neoplasia share similar risk
      factors: human papillomavirus infection, previous cervical intraepithelial
      neoplasia or cervical cancer, current smoking, sexual factors, and
      immunosuppression. Several treatment options are available for patients with
      documented histologic high-grade intraepithelial vulvar or vaginal neoplasia,
      including excision, laser vaporization, and 5-fluorouracil. After treatment,
      lifetime follow-up with cytology and colposcopy is recommended. With the
      widespread use of the human papillomavirus vaccine, one half to two thirds of
      vulvar and vaginal cancers may be prevented. Patient education regarding
      reduction of risk factors for progression and close surveillance of at-risk
      individuals may prevent the progression to invasive disease.

PMID- 18061871
TI  - An exploration of the potential impact of the designated driver campaign on
      bartenders' willingness to over-serve.
AB  - Much has been written about the impact of the presence of a designated driver on
      patrons' consumption, but heretofore, its impact on the behaviour of the server
      has been virtually ignored. The goal of this paper, then, was to explore the
      potential impact of the presence of a designated driver on alcoholic beverage
      servers' self-reported willingness to knowingly serve an already intoxicated
      customer. chi(2) analysis of survey data collected from 938 licensed servers, in
      the state of Indiana, USA, was performed. Approximately 43% of the bartenders
      surveyed reported that they either would be or might be willing to over-serve an
      already intoxicated customer. Of those who answered the follow-up question as to
      under what conditions they would be willing to over-serve, almost 80% reported
      that they would do so if the patron were accompanied by a designated driver. The
      statistical significance of the relationship between these two variables (.000)
      raises the question of whether the Designated Driver Campaign has the latent
      function of enabling some servers to neutralize their responsibility for over
      serving by disregarding other types of intoxication-related harm.

PMID- 18061872
TI  - The impact of substitution treatment in prisons--a literature review.
AB  - Substitution treatment (ST) has established itself as a generally recognised type
      of treatment for opioid dependence worldwide. Although the number of countries
      providing ST in prison has slowly started to grow over the last years, its
      application in the custody setting remains controversial. ST in prison is mainly
      employed in form of detoxification. Maintenance treatment is provided in only a
      limited number of international prisons. This literature review is centred around
      the question: "What is known about the effectiveness of prison based ST?"
      Furthermore, it investigates how this knowledge can be applied to improve
      treatment scope and quality. Effectiveness, as defined by the examined studies,
      refers to short- and long-term reduction of drug use and relapse, reduction in
      drug use related risk behaviours, reduction in criminal conduct and recidivism,
      facilitating the manageability of drug using prisoners and improving their
      physical stabilisation. In this context, substitute dosage, treatment duration,
      patient retention rates, complementary psycho-social care and the effects of
      disrupting maintenance treatment when entering the institution are scrutinised.
      Results show that prison-based ST and especially prison-based methadone
      maintenance treatment (PMMT) can reduce drug use and injection in penal
      institutions. Moreover, PMMT provision can reduce injecting risk behaviours as
      well as drugs charges and re-admission rates. However, for PMMT to retain
      patients in treatment and reduce illegal drug use and criminal behaviour a
      sufficiently high dose of methadone (e.g., >60 mg) and the treatment duration
      lasting the entire period of imprisonment appear crucial. On the basis of the
      analysed results the authors recommend the provision of PMMT for individuals with
      long-standing opioid dependence and suggest major expansions of prison based ST
      in many countries.

PMID- 18061873
TI  - Predictors of the degree of drug treatment coverage for injection drug users in
      94 metropolitan areas in the United States of America.
AB  - AIMS: A prior study concluded that drug treatment coverage, defined as the
      percentage of injection drug users in drug treatment, varied from 1 percent to 39
      percent (median 9 percent) in 96 metropolitan statistical areas (MSAs) in the
      United States. Here, we determine which metropolitan area characteristics are
      associated with drug treatment coverage. METHODS: We conducted secondary analysis
      of official data, including the number of injection drug users in treatment and
      other variables, for 94 large US MSAs. We estimated the number of injection drug
      users in these metropolitan areas using previously described methods. We used
      lagged cross-sectional analyses where the independent variables, chosen on the
      basis of a Theory of Community Action, preceded the dependent variable (drug
      treatment coverage) in time. Predictors were determined using ordinary least
      squares multiple regression and confirmed with robust regression. RESULTS:
      Independent predictors of higher drug treatment coverage for injectors were:
      presence of organisations that support treatment (unstandardized beta=1.64; 95
      percent CI .59 to 2.69); education expenditures per capita in the MSA
      (unstandardized beta=.12; 95 percent CI -.34 to 2.69); lower percentage of drug
      users in treatment who are non-injection drug users (unstandardized beta=-0.18;
      95 percent CI -0.24 to -0.12); higher percentage of the population who are non
      Hispanic White (unstandardized beta=.14; 95 percent CI .08 to .20); lower per
      capita long-term debt of governments in the metropolitan area (unstandardized
      beta=-0.93; 95 percent CI -1.51 to -0.35). CONCLUSIONS: In conditions of scarce
      treatment coverage for drug injectors, an indicator of epidemiologic need (the
      per capita extent of AIDS among injection drug users) does not predict treatment
      coverage, and competition for treatment slots by non-injectors may reduce
      injectors' access to treatment. Metropolitan finances limit treatment coverage.
      Political variables (racial structures, the presence of organisations that
      support drug treatment, and budget priorities) may be important determinants of
      treatment coverage for injectors. Although confidence in these results would be
      higher if we had used a longitudinal design, these results suggest that further
      research and action that address structural, political, and other barriers to
      treatment expansion are sorely needed.

PMID- 18061874
TI  - 'Treatment experienced' and 'treatment naive' drug agency clients compared.
AB  - BACKGROUND: Research on the prevalence and significance of previous treatment is
      limited, but indicates that many drug agency clients have had prior drug
      treatment experiences. Furthermore, treatment experienced drug users have
      different characteristics from treatment novices at treatment entry and poorer
      outcomes at follow up. METHODS: Data from a national longitudinal study of drug
      users entering treatment in Scotland were analysed using univariate and
      multivariate techniques to provide the first systematic comparison of treatment
      experienced and treatment naive drug users in the UK. Respondents (n=653) were
      interviewed on four separate occasions (treatment intake, 8 months, 16 months,
      and 33 months) using structured questionnaires. RESULTS: Five hundred and fifty
      eight individuals (85.5%) had had some form of previous treatment and many
      reported multiple previous treatments, most commonly substitute drugs. At
      treatment intake, treatment experienced respondents had worse drug use and life
      problems than treatment novices. Very high levels of illicit drug use (>85%) were
      reported by both treatment experienced and treatment naive drug users at all
      follow-ups, with no significant differences between the two groups at any time
      point. CONCLUSIONS: Drug users entering treatment in Scotland have routinely had
      multiple earlier treatments and report high levels of illicit drug use at follow
      up. Contrary to some earlier research, there is no evidence that those who are
      treatment experienced have worse drug use outcomes than those who are treatment
      naive. Findings add to the international literature on prior treatment
      experiences and new treatment clients' needs.

PMID- 18061875
TI  - Multi-level governance: The way forward for European illicit drug policy?
AB  - Illicit drug policy has long been an area that has attracted international policy
      intervention, however, the European Union has declared it an area of
      subsidiarity, leaving ultimate control to national governments. Nevertheless,
      European Union preoccupation with the illicit drug issue and international drug
      trafficking and organised crime concerns have ensured that continued and
      increased cooperation in illicit drug policy is never off the agenda. This
      article examines the history of European integration in contrasting areas of
      policy and considers both the desirability and the viability of an increasingly
      harmonised drug policy for Europe. Finally, it proposes a model of integrated
      illicit drug policy that is strongly connected to developing patterns of European
      social policy, calling on multi-level governance and close involvement at the
      level of the citizen.

PMID- 18061876
TI  - A sorcerer's apprentice and The Rule of Five: from rule-of-thumb to commandment
      and beyond.

PMID- 18061877
TI  - Pharmaceutical R&D in the spotlight: why is there still unmet medical need?
AB  - Huge amounts of money and knowledge have been poured into biomedical research for
      decades. Yet, in some disease areas next to no progress has been made in
      providing medical treatment. Importantly, it is not only neglected diseases where
      unmet medical need remains, but many diseases of 'rich' countries are also
      affected. Occasionally, new therapies exacerbate the medical need gap, such as in
      cancer. Our paper discusses some of the reasons why this might be and why all of
      society needs to find solutions to address unmet medical need.

PMID- 18061878
TI  - Unfinished business: target-based drug discovery.
AB  - The switch in the mid-1980s/early 1990s from a phenotypic approach to a target
      based approach to drug discovery has been followed by low productivity of new
      drugs entering the market. Reasons for the (necessary) switch and unsolved
      problems with both approaches to drug discovery are discussed. The S-curve theory
      of new technology development and introduction can act as guide as to when an
      upturn in productivity can be expected; this should occur during the next decade
      leading possibly to a new golden age of drug discovery.

PMID- 18061879
TI  - Multi-dimensional QSAR in drug discovery.
AB  - Quantitative structure-activity relationships (QSAR) is an area of computational
      research that builds virtual models to predict quantities such as the binding
      affinity or the toxic potential of existing or hypothetical molecules. Although a
      wealth of experimental data emphasizes the active role of the target protein in
      the binding process, QSAR studies are frequently restricted to the properties of
      the small-molecule ligand. This review aims at discussing recent QSAR concepts
      exploring higher dimensions (simulation of induced fit, simultaneous exploration
      of alternative binding modes, and solvation scenarios), and their benefit for the
      drug-discovery process.

PMID- 18061880
TI  - The role of mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modelling in
      translational research of biologics.
AB  - Lack of predictability of clinical efficacy and safety is an important problem
      facing pharmaceutical research today. Translational PK-PD has the ability to
      integrate data generated from diverse test platforms during discovery and
      development in a mechanistic framework. Therefore, successful implementation of
      translational PK-PD modelling and simulation early in the development cycle could
      have a substantial impact on overall efficiency and success of pharmaceutical
      research. Three case studies are presented, which outline successful
      implementation of the translational PK-PD methodology in the rational development
      of biotherapeutics across various stages of discovery and development. Emerging
      developments within the field are also discussed.

PMID- 18061881
TI  - One target-multiple indications: a call for an integrated common mechanisms
      strategy.
AB  - Ever-increasing research and development costs are putting constant pressure on
      the pharmaceutical industry to improve their efficiency. Efforts to increase the
      output of the research pipeline have yielded limited success. Traditionally,
      maximization of the value of a drug is attempted through life-cycle management,
      which is initiated late in development, or when the drug is already on the
      market. Validated targets can be exploited further through development of a
      follow-up drug, which may offer advantages regarding safety or convenience. In
      this article, we propose to systematically evaluate the full therapeutic
      potential of a drug target, proprietary chemical lead structure, or drug
      candidate as broad and as early as possible and we call this the 'common
      mechanism' approach.

PMID- 18061882
TI  - Integration of fragment screening and library design.
AB  - With more than 10 years of practical experience and theoretical analysis,
      fragment-based drug discovery (FBDD) has entered the mainstream of the
      pharmaceutical and biotech industries. An array of biophysical techniques has
      been used to detect the weak interaction between a fragment and the target. Each
      technique presents its own requirements regarding the fragment collection and the
      target; therefore, in order to optimize the potential of FBDD, the nature of the
      target should be a driving factor for simultaneous development of both the
      library and the screening technology. A roadmap is now available to guide
      fragment-to-lead evolution when structural information is available. The next
      challenge is to apply FBDD to targets for which high-resolution structural
      information is not available.

PMID- 18061883
TI  - Combating cardiovascular disease with angiogenic therapy.
AB  - For over a decade we have lived with the promise that therapeutic angiogenesis,
      defined as the growth of new blood vessels in tissues damaged by poor blood
      perfusion, would provide a lasting clinical benefit to patients suffering from
      cardiovascular disease, the leading cause of death in the Western world. Numerous
      successful protein, gene and cell-based angiogenesis studies in animals with
      experimentally induced ischemia have not been followed by positive efficacy data
      in human trials. Armed with knowledge of the shortcomings of earlier clinical
      studies, emerging results from more recent trials indicate that protein-based
      angiogenesis therapy may provide a viable treatment option for patients suffering
      from advanced atherosclerotic disease.

PMID- 18061884
TI  - An overview of automated systems relevant in pharmaceutical salt screening.
AB  - Modern drug discovery and development tools have evolved persistently to meet the
      demands of the highly competitive environment of the pharmaceutical industry.
      This has introduced high-throughput methodologies in various stages of drug
      development. Salt screening is an integral part of the preformulation stage of
      drug development and is increasingly being adapted to 'high-throughput
      experimentation' (HTE), to shortlist the potential salt(s) for a comprehensive
      biopharmaceutical characterization at the scale-up stage. The selected salt form
      may then be forwarded to the next stage of drug development. This review provides
      an overview of 'high-throughput experimentation' methodology for selection of an
      optimal drug salt candidate.

PMID- 18061885
TI  - Pharmacogenetics of EGFR and VEGF inhibition.
AB  - Even though treatment of several types of solid tumours has improved in the past
      few years with the introduction of the monoclonal antibodies against epidermal
      growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF),
      response rates to these targeted therapies are modest. Pharmacogenetic factors
      have the potential to select patients with higher chance of response to agents
      that target these pathways. This review provides an overview over germ-line
      variations in genes that are potentially involved in the pharmacodynamics of the
      monoclonal antibodies cetuximab, panitumumab and bevacizumab, and which may
      underlie variable anti-tumour response.

PMID- 18061886
TI  - Status of terpenes as skin penetration enhancers.
AB  - Since its introduction, transdermal drug delivery has promised much but, in some
      respects has still to deliver on that initial promise, due to inherent
      limitations imposed by the percutaneous route. The greatest obstacle for
      transdermal delivery is the barrier property of the stratum corneum. Many
      approaches have been employed to breach the skin barrier, of which, the most
      widely used one is that of chemical penetration enhancers. Of the penetration
      enhancers, terpenes are arguably the most highly advanced and proven category and
      are classified as generally regarded as safe (GRAS) by the Food and Drug
      Administration. This paper presents an overview of the investigations on the
      feasibility and application of terpenes as sorption promoters for improved
      delivery of drugs through skin.

PMID- 18061887
TI  - Solid dispersions as strategy to improve oral bioavailability of poor water
      soluble drugs.
AB  - Solid dispersions are one of the most promising strategies to improve the oral
      bioavailability of poorly water soluble drugs. By reducing drug particle size to
      the absolute minimum, and hence improving drug wettability, bioavailability may
      be significantly improved. They are usually presented as amorphous products,
      mainly obtained by two major different methods, for example, melting and solvent
      evaporation. Recently, surfactants have been included to stabilize the
      formulations, thus avoiding drug recrystallization and potentiating their
      solubility. New manufacturing processes to obtain solid dispersions have also
      been developed to reduce the drawbacks of the initial process. In this review, it
      is intended to discuss the recent advances related on the area of solid
      dispersions.

PMID- 18061888
TI  - The highly permeable blood-brain barrier: an evaluation of current opinions about
      brain uptake capacity.
AB  - The blood-brain barrier is often perceived as relatively impermeable, and various
      cut-off values for zero or limited brain permeability have been suggested. The
      validity of these values has been evaluated in this review. The barrier appears
      to have a very high permeability and absorptive capacity: sufficient to absorb
      compounds with polar surface area >270 A(2), molecular weight > 1,000 Da, log D <
      -3.5 and equilibrium brain-to-blood concentration ratio <0.01 well. Sufficient
      intestinal uptake indicates good passive brain uptake potential. The uptake is
      potentially more sensitive to involvement and changes of active transport than in
      the intestines. A physiologically based in vitro-in vivo method for prediction of
      brain uptake is presented.

PMID- 18061896
TI  - Biotechnological valorization potential indicator for lignocellulosic materials.
AB  - This report introduces the biotechnological valorization potential indicator
      (BVPI) concept, a metric to measure the degree of suitability of lignocellulosic
      materials to be used as feedstock in a biorefinery framework. This indicator
      groups the impact of the main factors influencing upgrade-ability, both the
      biological/chemical nature of the materials, and the economical, technological
      and geographical factors. The BVPI was applied to the identification of the most
      relevant opportunities and constraints pertaining to the lignocellulosic by
      products from the Portuguese agro-industrial cluster. Several by-products were
      identified with a high valorization potential, e.g., rice husks, brewery's spent
      grain, tomato pomace, carob pulp, de-alcoholized grape bagasse, and extracted
      olive bagasse, that would greatly benefit from the further development of
      specific biotechnology processes, specifically concerning the upgrade of their
      hemicellulosic fraction.

PMID- 18061902
TI  - Editorial: Food vs fuel--the role of biotechnology.

PMID- 18061904
TI  - Perspective: Food vs mobility.

PMID- 18061908
TI  - Biotech history: about Professor Arnold Demain.

PMID- 18061909
TI  - PtCl4-catalyzed domino synthesis of fused bicyclic acetals.

PMID- 18061910
TI  - Ratiometric fluorescent biosensor for real-time and label-free monitoring of fine
      saccharide metabolic pathways.

PMID- 18061911
TI  - Pyrazolyl-diamine ligands that bear anthracenyl moieties and their rhenium(I)
      tricarbonyl complexes: synthesis, characterisation and DNA-binding properties.
AB  - Two novel families of pyrazolyl-diamine ligands that bear an anthracen-9-yl group
      as a DNA-binding fragment, pz*(CH2)2NH(CH2)2NHCH2-9-anthryl (pz*=pz (L(1)), 3,5
      Me2pz (L2)) and pz*(CH2)2NH(CH2)2NH(2 (pz*=4-(9-anthrylmethyl)pz (L3), 3,5-Me2-4
      (9-anthrylmethyl)pz (L4)), have been prepared and fully characterised. In the
      case of L2-L4, the evaluation of their coordination capability towards the fac
      [Re(CO)3]+ core led to the synthesis of the organometallic complexes fac
      [Re(CO)(3){3,5-Me(2)pz(CH2)2NH(CH2)2NHCH2-9-anthryl}]Br (7) and fac-[Re(CO)3{4-(9
      anthrylmethyl)pz*(CH2)2NH(CH2)2NH2}]Br (pz*=pz (8), 3,5-Me2pz 9). The interaction
      of the novel pyrazole-diamine ligands and the rhenium(I) complexes with calf
      thymus (CT) DNA has been investigated with a variety of spectroscopic techniques
      (UV-visible, fluorescence, circular dichroism (CD) and linear dichroism (LD)).
      All of the evaluated compounds have a moderate affinity to CT DNA
      (3.46x10(3)<K(b)<1.95x10(4)), but the binding mode depends on the position of the
      chromophore in the framework of the pyrazolyl-diamine ligands. LD measurements
      have shown that L1 and L2 act as DNA intercalators, but complex 7 intercalates
      only partially. By contrast, the compounds with the anthracenyl group at the 4
      position of the azolyl ring (L(3), L4 and 9) do not intercalate, and behave more
      like DNA groove binders. Fluorescence microscopy studies have demonstrated that
      complexes 7 and 9 can target the nucleus of murine B16-F1 melanoma cells, and
      appear to be promising platforms for the further design of radiopharmaceuticals
      for targeted radiotherapy.

PMID- 18061912
TI  - Polyvinyl-locked versus free quaterthiophene: effect of spatial constraints on
      the electronic properties of n-hexylquaterthiophene.
AB  - A soluble, low-weight fraction of poly(alpha-vinyl,omega-n-hexyl
      quaterthiophene), PT4Hex, having n-hexylquaterthiophenes as side-chain groups, is
      prepared by free-radical polymerization of alpha-vinyl,omega-n-hexyl
      quaterthiophene and the corresponding properties compared to those of free di-n
      hexylquaterthiophene (T4Hex). Optical analysis (absorption and emission) and X
      ray diffraction data indicate that in the polyvinyl-locked architecture the
      quaterthiophene pendants adopt a cofacial arrangement with a mutual distance
      close enough for pi-pi orbitals to overlap ( approximately 4 A). As a consequence
      of the close chain packing, a shift of the reduction potential of about 0.5 V
      toward less negative values with respect to free T4Hex, is found for PT4Hex
      films. Due to its enhanced electron affinity, PT4Hex displays an electron
      acceptor behavior when blended with alkylated and silylated quaterthiophenes
      acting as donors.

PMID- 18061913
TI  - Extending the scope of singlet-state spectroscopy.
AB  - Different decoupling sequences are tested-using various shaped radio-frequency
      (RF) pulses-to achieve the longest possible lifetimes of singlet-state
      populations over the widest possible bandwidths, that is, ranges of offsets and
      relative chemical shifts of the nuclei involved in the singlet states. The use of
      sinc or refocusing broadband universal rotation pulses (RE-BURP) for decoupling
      during the intervals where singlet-state populations are preserved allows one to
      extend the useful bandwidth with respect to prior state-of-the-art methods based
      on composite-pulse WALTZ decoupling. The improved sinc decoupling sequences
      afford a more reliable and sensitive measure of the lifetimes of singlet states
      in pairs of spins that have widely different chemical shifts, such as the two
      aromatic protons H(5) and H(6) in uracil. Similar advantages are expected for
      nucleotides in RNA and DNA. Alternative approaches, in particular frequency
      modulated decoupling sequences, also appear to be effective in preserving singlet
      state populations, even though the profiles of the apparent relaxation rate
      constants as a function of the offset are somewhat perturbed. The best decoupling
      sequences prove their utility in sustaining longer lifetimes of singlet states
      than previously achieved for the side-chain tyrosine protons in bovine pancreatic
      trypsin inhibitor (BPTI) at 600 MHz (14.1 T), where the differences of chemical
      shifts between coupled protons are a challenge.

PMID- 18061914
TI  - Quantitative online detection of low-concentrated drugs via a SERS microfluidic
      system.
AB  - Herein, quantitative online monitoring of concentration fluctuations of different
      interesting drugs, namely, the phenothiazine promethazine as well as the anti
      cancer agent mitoxantrone via surface enhanced Raman scattering assay based on a
      microfluidic device is demonstrated. With the applied liquid/liquid two-phase
      segmented flow system we succeed in preventing the adhesion of nanoparticle
      aggregates to the channel walls which is necessary for a quantitative analysis.
      Even after repeated cycles no carry-over due to sedimentation of colloid
      particles is observed. To the best of our knowledge these are the first
      measurements applying a combination of a microfluidic device with SERS detection
      for quantitative online monitoring of fluctuations in drug concentrations over
      hours without use of aggressive chemicals for rinsing the chip surfaces prior to
      each measurement.

PMID- 18061915
TI  - Mechanism of thermal toluene autoxidation.
AB  - Aerobic oxidation of toluene (PhCH3) is investigated by complementary
      experimental and theoretical methodologies. Whereas the reaction of the chain
      carrying benzylperoxyl radicals with the substrate produces predominantly benzyl
      hydroperoxide, benzyl alcohol and benzaldehyde originate mainly from subsequent
      propagation of the hydroperoxide product. Nevertheless, a significant fraction of
      benzaldehyde is also produced in primary PhCH3 propagation, presumably via proton
      rather than hydrogen transfer. An equimolar amount of benzyl alcohol, together
      with benzoic acid, is additionally produced in the tertiary propagation of PhCHO
      with benzylperoxyl radicals. The "hot" oxy radicals generated in this step can
      also abstract aromatic hydrogen atoms from PhCH3, and this results in production
      of cresols, known inhibitors of radical-chain reactions. The very fast benzyl
      peroxyl-initiated co-oxidation of benzyl alcohol generates HO2* radicals, along
      with benzaldehyde. This reaction also causes a decrease in the overall oxidation
      rate, due to the fast chain-terminating reaction of HO2*with the benzylperoxyl
      radicals, which causes a loss of chain carriers. Moreover, due to the fast
      equilibrium PhCH2OOH+HO2* right harpoon over left harpoonPhCH2OO* + H2O2, and the
      much lower reactivity of H2O2 compared to PhCH2OOH, the fast co-oxidation of the
      alcohol means that HO2* gradually takes over the role of benzylperoxyl as
      principal chain carrier. This drastically changes the autoxidation mechanism and,
      among other things, causes a sharp decrease in the hydroperoxide yield.

PMID- 18061916
TI  - The Menshutkin reaction in the gas phase and in aqueous solution: a valence bond
      study.
AB  - The recently developed (L. Song, W. Wu, Q. Zhang, S. Shaik, J. Phys. Chem. A
      2004, 108, 6017-6024) valence bond method coupled to a polarized continuum model
      (VBPCM) is applied to the Menshutkin reaction, NH3+CH3Cl-->CH3NH3(+)+Cl-, in the
      gas phase and in aqueous solution. The computed barriers and reaction energies at
      the level of the breathing orbital VB method (P. C. Hiberty, J. P. Flament, E.
      Noizet, Chem. Phys. Lett. 1992, 189, 259), BOVB and VBPCM//BOVB, are comparable
      to CCSD(T) and CCSD(T)//PCM results and to experimental values in solution. The
      gas-phase reaction is endothermic and leads to an ion-pair complex via a late
      transition state. By contrast, the reaction in the aqueous phase is exothermic
      and leads to separate solvated ions as reaction products, via an early transition
      state. The VB calculations provide also the reactivity parameters needed to apply
      the valence bond state correlation diagram method, VBSCD (S. Shaik, A. Shurki,
      Angew. Chem. Int. Ed. 1999, 38, 586). It is shown that the reactivity parameters
      along with their semiempirical derivations provide together a satisfactory
      qualitative and quantitative account of the barriers.

PMID- 18061917
TI  - On the use of PIPSA to guide target-selective drug design.

PMID- 18061918
TI  - Molecular models of the interface between anterior pharynx-defective protein 1
      (APH-1) and presenilin involving GxxxG motifs.
AB  - Gamma-secretase is an integral membrane protease, which is a complex of four
      membrane proteins. Improper functioning of gamma-secretase was found to be
      critical in the pathogenesis of Alzheimer's disease. Despite numerous efforts,
      the structure of the protease as well as its proteolytic mechanism remains poorly
      understood. In this work we constructed a model of interactions between two
      proteins forming gamma-secretase: APH-1 and presenilin. This interface is based
      on a highly conserved GxxxGxxxG motif in the APH-1 protein. It can form a tight
      contact with a small-residue AxxxAxxxG motif in presenilin. Here, four binding
      modes based on similar structures involving GxxxG motifs in glycophorin and
      aquaporin were proposed and verified. The resulting best model employs
      antiparallel orientations of interacting helices and is in agreement with the
      currently accepted topology of both proteins. This model can be used for further
      structural characterization of gamma-secretase and its components.

PMID- 18061919
TI  - A composite model for HERG blockade.
AB  - hERG blockade is one of the major toxicological problems in lead structure
      optimization. Reliable ligand-based in silico models for predicting hERG blockade
      therefore have considerable potential for saving time and money, as patch-clamp
      measurements are very expensive and no crystal structures of the hERG-encoded
      channel are available. Herein we present a predictive QSAR model for hERG
      blockade that differentiates between specific and nonspecific binding. Specific
      binders are identified by preliminary pharmacophore scanning. In addition to
      descriptor-based models for the compounds selected as hitting one of two
      different pharmacophores, we also use a model for nonspecific binding that
      reproduces blocking properties of molecules that do not fit either of the two
      pharmacophores. PLS and SVR models based on interpretable quantum mechanically
      derived descriptors on a literature dataset of 113 molecules reach overall R(2)
      values between 0.60 and 0.70 for independent validation sets and R(2) values
      between 0.39 and 0.76 after partitioning according to the pharmacophore search
      for the test sets. Our findings suggest that hERG blockade may occur through
      different types of binding, so that several different models may be necessary to
      assess hERG toxicity.

PMID- 18061921
TI  - Poly(amido amine)s as gene delivery vectors: effects of quaternary nicotinamide
      moieties in the side chains.
AB  - To evaluate the effect of quaternary nicotinamide pendant groups on gene delivery
      properties, a series of poly(amido amine) (co)polymers were synthesized by
      Michael addition polymerization of N, N'-cystaminebisacrylamide with variable
      ratios of 1-(4-aminobutyl)-3-carbamoylpyridinium (Nic-BuNH(2)), and tert-butyl-4
      aminobutyl carbamate (BocNH-BuNH(2)), yielding poly(amido amine)s (NicX-NHBoc)
      with X=0, 10, 30, and 50 % of quaternary nicotinamide groups in the polymer side
      chains. Deprotection of the pendant Boc-NH groups afforded an analogous series of
      polymers (NicX-NH(2)) with higher charge density (due to the presence of
      protonated primary amino groups in the side chains) and subsequent acetylation
      yielded a series of polymers (NicX-NHAc) of lower hydrophobicity than the Boc
      protected polymers. The polymers with the Boc-protected or the acetylated amino
      groups showed high buffer capacity in the range pH 5.1-7.4, which is a property
      that can contribute to endosomal escape of polyplexes. The presence of quaternary
      nicotinamide groups has distinct beneficial effects on the gene vector properties
      of these polymers. The polymers containing >or=30 % of quaternary nicotinamide
      groups in their side chains condense DNA into small, nanosized particles (<or=200
      nm) with positive surface charge (>or=+15 mV). Fluorescence experiments using
      ethidium bromide as a competitor showed that the quaternary nicotinamide groups
      intercalate with DNA, contributing to a more intimate polymer-DNA binding and
      shielding. Polyplexes of nicotinamide-functionalized poly(amido amine)s NicX
      NHBoc and NicX-NHAc, formed at 12/1 polymerDNA mass ratio, efficiently transfect
      COS-7 cells with efficacies up to four times higher than that of PEI (Exgen 500),
      and with essentially absence of cytotoxicity. NicX-NH(2) polymers, possessing
      protonated primary amino groups in their side chains, have a higher cytotoxicity
      profile under these conditions, but at lower 3/1 polymer-DNA mass ratio also
      these polymers are capable of efficient transfection, while retaining full cell
      viability.

PMID- 18061920
TI  - Medicinal chemistry aspects of drug targets in sphingolipid metabolism.

PMID- 18061922
TI  - Total synthesis of epohelmin B and its analogues.
AB  - A concise synthesis of the pyrrolizidine alkaloid epohelmin B (1) and a series of
      analogues is described. The key steps en route to this lanosterol synthase
      (oxidosqualene cyclase) inhibitor comprise a highly practical "azonia-Cope
      rearrangement", which sets the chiral amine center with excellent optical purity,
      a ring-closing metathesis (RCM) reaction catalyzed by a readily prepared and now
      also commercially available ruthenium-indenylidene complex, a manganese-catalyzed
      epoxidation of the resulting eight-membered cycloalkene derivative, and a nosyl
      deprotection/transannular-epoxide-opening cascade to forge the pyrrolizidine
      core. Digression from the route leading to the natural product in the final
      stages allowed for the preparation of several "epohelmin-like" compounds with
      modified side chains, which is necessary for investigations into a possible
      functional relationship with other known lanosterol synthase inhibitors.

PMID- 18061923
TI  - The rate-determining step in the rhodium-xantphos-catalysed hydroformylation of 1
      octene.
AB  - The rate-determining step in the hydroformylation of 1-octene, catalysed by the
      rhodium-Xantphos catalyst system, was determined by using a combination of
      experimentally determined (1)H/(2)H and (12)C/(13)C kinetic isotope effects and a
      theoretical approach. From the rates of hydroformylation and deuterioformylation,
      a small (1)H/(2)H isotope effect of 1.2 was determined for the hydride moiety of
      the rhodium catalyst. (12)C/(13)C isotope effects of 1.012(1) and 1.012(3) for
      the alpha-carbon and beta-carbon atoms of 1-octene were determined, respectively.
      Both quantum mechanics/molecular mechanics (QM/MM) and full quantum mechanics
      calculations were carried out on the key catalytic steps, for "real-world" ligand
      systems, to clarify whether alkene coordination or hydride migration is the rate
      determining step. Our calculations (21.4 kcal mol(-1)) quantitatively reproduce
      the experimental energy barrier for CO dissociation (20.1 kcal mol(-1)) starting
      at the (bisphosphane)RhH(CO)(2) resting state. The barrier for hydride migration
      lies 3.8 kcal mol(-1) higher than the barrier for CO dissociation (experimentally
      determined trend approximately 3 kcal mol(-1)). The computed (1)H/(2)H and
      (12)C/(13)C kinetic isotope effects corroborate the results of the energy
      analysis.

PMID- 18061925
TI  - Immunochemical and single molecule force spectroscopy studies of specific
      interaction between the laminin binding protein and the West Nile virus surface
      glycoprotein E domain II.
AB  - ELISA and Western blot immunochemical data attest an effective and highly
      specific interaction of the surface glycoprotein E domain II (DII) of the tick
      born encephalitis and Dengue viruses with the laminin binding protein (LBP).
      Based on a highly conservative structure of the DII in different flaviviruses we
      propose a similarly effective interaction between the LBP and the DII of the
      surface glycoprotein E of the West Nile virus. We report the results of studies
      of this interaction by immunochemical and single molecule force spectroscopy
      methods. The specific binding between these species is confirmed by both methods.

PMID- 18061927
TI  - Interconnections and independence: Heinrich Wieland (1877-1957) and his era.

PMID- 18061928
TI  - Inside cover: total synthesis and configurational assignment of pasteurestin a
      and B (Angew. Chem. Int. Ed. 48/2007).

PMID- 18061931
TI  - Micronutrient mixture in tumor growth and metastasis.

PMID- 18061932
TI  - The role of hemophagocytosis in bone marrow aspirates in the diagnosis of
      hemophagocytic lymphohistiocytosis.

PMID- 18061933
TI  - Relative tumor burden predicts metastasis-free survival in pediatric
      osteosarcoma.
AB  - BACKGROUND: To analyze the significance of relative tumor burden in pediatric
      osteosarcoma. METHODS: We retrospectively reviewed 241 patients with localized
      pediatric osteosarcoma and measured tumor size on MR images at presentation.
      Absolute tumor size parameters measured on MR images were converted to relative
      values by dividing body surface area. Both absolute and relative size parameters
      were analyzed for their correlation with metastasis-free survival (MFS). RESULTS:
      The 5-year MFS was 67.5 +/- 3.1%, with median follow-up of 72 months (range, 8
      205 months). In addition to poor histologic response (RR 3.24; 95% CI: 1.99-5.28;
      P < 0.001), large relative tumor plane (RTP; RR 3.28; 95% CI: 1.72-6.25; P <
      0.001), large relative tumor area (RTA; RR 4.14; 95% CI: 1.53-11.22; P = 0.005),
      and large absolute tumor width (ATW; RR; 3.10; 95% CI: 1.23-7.79; P = 0.02)
      shortened the MFS. When survival was analyzed by combining RTP and histologic
      response, patients with small RTP and a good response showed the best survival (5
      year MFS of 90.2 +/- 3.6%), while those with large RTP and a poor response showed
      the worst survival (5-year MFS of 45.1 +/- 6.6%). CONCLUSION: Relative two
      dimensional tumor size parameters (RTP and RTA) rather than absolute values are
      useful prognostic factors in pediatric osteosarcoma patients.

PMID- 18061935
TI  - Rest-induced suppression of anterior horn cell excitability as measured by F
      waves: comparison between volitionally inactivated and control muscles.
AB  - To test the hypothesis that the anterior horn cells become hypoexcitable in the
      absence of central drive, we recorded F waves simultaneously from the first
      dorsal interosseous (FDI) and the abductor digiti minimi (ADM) before and after
      volitionally inactivating one muscle (target) while periodically contracting the
      other muscle (control). In 14 healthy subjects, F waves recorded from the target
      muscle showed a progressive decrease in persistence and amplitude (whether
      counting all 100 trials or only detectable responses) after muscle relaxation for
      1, 3, and 6 hours, followed by a quick recovery upon brief muscle contraction. We
      conclude that volitional inactivation suppresses the F waves of the target muscle
      without equally affecting the control muscle innervated by the same nerve. The
      history of activity of a muscle should therefore be taken into account in
      clinical testing, especially when the study of a paretic muscle shows abnormal F
      wave excitability.

PMID- 18061936
TI  - Changes in short afferent inhibition during phasic movement in focal dystonia.
AB  - Impaired surround inhibition could account for the abnormal motor control seen in
      patients with focal hand dystonia, but the neural mechanisms underlying surround
      inhibition in the motor system are not known. We sought to determine whether an
      abnormality of the influence of sensory input at short latency could contribute
      to the deficit of surround inhibition in patients with focal hand dystonia (FHD).
      To measure digital short afferent inhibition (dSAI), subjects received electrical
      stimulation at the digit followed after 23 ms by transcranial magnetic
      stimulation (TMS). Motor evoked potentials (MEPs) were recorded over abductor
      digiti minimi (ADM) during rest and during voluntary phasic flexion of the second
      digit. F-waves were also recorded. We studied 13 FHD patients and 17 healthy
      volunteers. FHD patients had increased homotopic dSAI in ADM during flexion of
      the second digit, suggesting that this process acts to diminish overflow during
      movement; this might be a compensatory mechanism. No group differences were
      observed in first dorsal interosseous. Further, no differences were seen in the F
      waves between groups, suggesting that the changes in dSAI are mediated at the
      cortical level rather than at the spinal cord. Understanding the role of these
      inhibitory circuits in dystonia may lead to development of therapeutic agents
      aimed at restoring inhibition.

PMID- 18061937
TI  - Autoantibody-mediated bowel and bladder dysfunction in a patient with chronic,
      nondiabetic neuropathy.
AB  - Physiological techniques can be used to detect novel autoantibodies causing
      alteration of autonomic function after passive transfer to mice. Previously, such
      antibodies have been detected in patients with type I diabetes mellitus,
      myasthenia gravis, and Sjogren's syndrome. We now describe a patient with an
      idiopathic nondiabetic neuropathy with prominent autonomic symptoms, including
      bladder and bowel dysfunction. Physiological assays of whole colon and bladder
      were used to determine the presence in the patient serum of functional
      autoantibodies capable of mediating autonomic dysfunction. Immunoglobulin G (IgG)
      from this patient was able to disrupt bladder and bowel function on passive
      transfer to mice. This is a new pattern of autoantibody-mediated abnormality.
      Although the target antigen is unknown, it is likely to be a cell-surface
      receptor or ion channel. This case highlights the usefulness of passive transfer
      studies in detecting functional antibodies in patients with autonomic neuropathy.

PMID- 18061938
TI  - A new biomarker for mitotic cells.
AB  - Many epitopes are phosphorylated during mitosis. These epitopes are useful
      biomarkers for mitotic cells. The most commonly used are MPM-2 and serine 10 of
      histone H3. Here we investigated the use of an antibody generated against a
      phospho peptide matching residues 774-788 of the human retinoblastoma protein 1
      (Rb) to detect mitotic cells. Human cell lines were stained with DNA dyes and
      antibodies reactive with epitopes defined by antibody MPM-2, phospho-S10-histone
      H3, and the phospho-serine peptide, TRPPTLSPIPHIPRC (phospho-S780-Rb).
      Immunoreactivity and DNA content were measured by flow and image cytometry.
      Correlation and pattern recognition analyses were performed on list mode data.
      Western blots and immunoprecipitation were used to investigate the number of
      peptides reactive with phospho-S780-Rb and the relationship between reactivity
      with this antibody and MPM-2. Costaining for bromodeoxyuridine (BrdU) was used to
      determine acid resistance of the phospho-S780-Rb epitope. Cell cycle related
      phospho-S780-Rb immunofluorescence correlated strongly with that of MPM-2. Laser
      scanning cytometry showed that phospho-S780-Rb immunofluorescence is expressed at
      high levels on all stages of mitotic cells. Western blotting and
      immunoprecipitation showed that the epitope is expressed on several peptides
      including Rb protein. Costaining of BrdU showed that the epitope is stable to
      acid. Kinetic experiments showed utility in complex cell cycle analysis aimed at
      measuring cell cycle transition state timing. The phospho-S780-Rb epitope is a
      robust marker of mitosis that allows cytometric detection of mitotic cells
      beginning with chromatin condensation and ending after cytokinesis. Costaining of
      cells with DNA dyes allows discrimination and counting of mitotic cells and post
      cytokinetic ("newborn") cells. To facilitate use without confusion about
      specificity, we suggest the trivial name, pS780 for this mitotic epitope.

PMID- 18061939
TI  - Crypt loss, pericapillary hemorrhage, and severe gastrointestinal graft-versus
      host disease.

PMID- 18061940
TI  - Obesity, bariatric surgery, and iron deficiency: true, true, true and related.
AB  - Morbid obesity is a health problem that has been shown to be refractory to diet,
      exercise, and medical treatment. Surgeries designed to promote weight loss,
      termed bariatric surgery and typically involving a gastric bypass procedure, have
      recently been implemented to treat obesity with high success rates. However, long
      term sequelae can result in micronutrient deficiencies. This review will focus on
      iron deficiency and its association with obesity and bariatric surgery. Iron
      deficiency develops after gastric bypass for several reasons including
      intolerance for red meat, diminished gastric acid secretion, and exclusion of the
      duodenum from the alimentary tract. Menstruating women, pregnant women, and
      adolescents may be particularly predisposed toward developing iron deficiency and
      microcytic anemias after bypass surgery. Preoperative assessment of patients
      should include a complete hematological work-up, including measurement of iron
      stores. Postoperatively, oral iron prophylaxis and vitamin C in addition to a
      multivitamin should be prescribed for bypass patients, especially for vulnerable
      populations. Once iron deficiency has developed, it may prove refractory to oral
      treatment, and require parenteral iron, blood transfusions, or surgical
      interventions. Bariatric surgery patients require lifelong follow-up of
      hematological and iron parameters since iron deficiency and anemia may develop
      years after surgery.

PMID- 18061941
TI  - Polymorphisms in xenobiotic-metabolizing genes and the risk of chronic
      lymphocytic leukemia and non-Hodgkin's lymphoma in adult Russian patients.
AB  - Polymorphisms in genes coding xenobiotic-metabolizing enzymes are considered as
      risk factors modifying susceptibility to cancer. We developed a biochip for the
      analysis of 18 mutations in 10 genes of metabolizing system: CYP1A1, CYP2D6,
      GSTT1, GSTM1, MTHFR, MTRR, NQO1, CYP2C9, CYP2C19, and NAT2. Using allele-specific
      hybridization on the biochip 76 T-cell non-Hodgkin's lymphoma (NHL) patients, 83
      B-cell chronic lymphocytic leukemia (B-CLL) patients, and 177 healthy donors were
      tested. Polymorphic CYP1A1 alleles were more frequent in B-CLL patients relative
      to normal controls, for example, a combination of polymorphic variants 4887C > A,
      4889A > G, and 6235T > C (OR = 1.76, 95% CI = 1.0-3.1). The GSTM1 null genotype
      was more frequent in NHL patients relative to controls (OR = 1.82, 95% CI = 1.1
      3.1). The combination of unfavorable polymorphic CYP1A1 variants and GSTM1 null
      genotype was found more frequently in B-CLL patients relative to controls (OR =
      2.52, 95% CI = 1.3-4.9). In addition, male B-CLL patients demonstrated a
      significantly increased occurrence of heterozygous and homozygous allele *2 of
      CYP2C9 gene (OR = 2.38, 95% CI = 1.1-5.2) as well as a combination of alleles *2
      and *3 of the gene (OR = 2.09, 95% CI = 1.1-3.9). Thus, our findings show the
      association between polymorphic alleles of CYP1A1, GSTM1, and CYP2C9 genes and
      the risk to develop NHL or B-CLL. The developed biochip can be considered as a
      convenient analytical tool for research studies and predictive analysis in
      oncohematology.

PMID- 18061942
TI  - Dynamics of ultrastructural changes in the isolated crayfish mechanoreceptor
      neuron under photodynamic impact.
AB  - Photodynamic therapy (PDT) is used for treatment of cancer, including brain
      tumors. To explore the mechanism of photodynamic injury of neurons, we studied
      the PDT effect of 10(-7) M Photosens on ultrastructure of isolated crayfish
      stretch receptor neuron that was used as a model object. After a 5-min treatment
      that only slightly changed neuron activity, the initial injury (alteration of
      some mitochondria, vacuolization of the cytoplasm) was observed in parallel with
      compensatory changes (chromatin decondensation, elongation and aggregation of
      mitochondria, formation of lysosomes and autophagosomes). Longer
      photosensitization (30 min) abolished firing, destroyed mitochondria and Golgi
      apparatus, depleted energy sources (glycogen granules), and impaired granular
      endoplasmic reticulum and polysomes involved in protein synthesis. Therefore,
      mitochondria and Golgi apparatus were the primary targets for Photosens-mediated
      PDT in a single neuron. Their alteration might underlie functional shifts. These
      structural changes continued to develop after abolishment of neuronal activity
      and led to necrosis.

PMID- 18061944
TI  - Molecular basis for detection of invading pathogens in the brain.
AB  - Classical immunology textbooks have described the central nervous system as an
      immune-privileged site, i.e., as devoid of inflammatory and host-vs.-graft
      immunoreactions. This view has been refined, since we now know that hematopoietic
      cells infiltrate the CNS under certain circumstances and that CNS-resident cells
      are capable of launching an innate immune response. Microglia cells express an
      extensive repertoire of pattern-recognition receptors and act as sentinels
      surveilling the CNS for possible damage or infection. Astrocytes are the most
      abundant cell type in the brain, and they are capable of launching a strong
      supportive innate immune response. Novel findings show that both astrocytes and,
      surprisingly, even neurons express pattern-recognition receptors. Activation of
      these receptors leads to a functional response, indicating that cells other than
      microglia are capable of initiating a primary innate immune response against CNS
      invading pathogens. Here, we put these findings into context with what has been
      learned from recent in vitro and in vivo experiments about the initiation of an
      innate immune response in the brain.

PMID- 18061943
TI  - Small heat shock proteins Hsp27 or alphaB-crystallin and the protein components
      of neurofibrillary tangles: tau and neurofilaments.
AB  - The heat-shock proteins (HSPs) Hsp27 and alphaB-crystallin are up-regulated in
      Alzheimer's disease (AD), but the extent of this and the consequences are still
      largely unknown. The HSPs are involved in protein degradation and protection
      against protein aggregation, and they interact with several cytoskeletal
      components such as microtubules (MT) and neurofilaments (NF). AD pathology
      includes aggregated proteins (tau, NF), decreased protein degradation, and
      cytoskeletal disruption. It is thus of interest to investigate more closely the
      possible roles of the HSPs in AD pathology. The expressions of Hsp27 and alphaB
      crystallin in AD brain samples were significantly increased (by approximately 20%
      and approximately 30%, respectively) and correlated significantly with
      phosphorylated tau and NF proteins. To investigate the consequences of increased
      HSP levels on tau and NF regulation, N2a cells were transfected with Hsp27 or
      alphaB-crystallin constructs, and overexpression of the HSPs was confirmed in the
      cells. Increased tau phosphorylation at the Ser262 site in the N2a cells was
      regulated by Hsp27 overexpression (possibly through p70S6k), whereas the
      overexpression of alphaB-crystallin resulted in decreased levels of
      phosphorylated tau, NF, and GSK-3beta. It was also shown that overexpression of
      HSPs causes an increase in the percentage of cells present in the G(1) phase. The
      results presented suggest that a cellular defense against dysregulated proteins,
      in the form of Hsp27 and alphaB-crystallin, might contribute to the cell cycle
      reentry seen in AD cells. Furthermore, Hsp27 might also be involved in AD
      pathology by aggravating MT disruption by tau phosphorylation.

PMID- 18061945
TI  - Comparative flow immunophenotypic features of the inflammatory infiltrates of
      Hodgkin lymphoma and lymphoid hyperplasia.
AB  - BACKGROUND: Hodgkin lymphoma (HL) is characterized by relatively few malignant
      Reed-Sternberg (RS) cells admixed within a reactive T cell rich inflammatory
      infiltrate. There is growing recognition that the HL-associated inflammatory
      milieu may enhance rather than inhibit growth of RS tumor cells. Since little is
      known of the immunophenotype of the HL inflammatory infiltrate we have performed
      a detailed retrospective comparison of the flow immunophenotype of HL and
      reactive lymphoid hyperplasia (RLH) to identify HL-specific immunophenotypic
      features. METHODS: Single cell suspensions from 59 lymph nodes involved by HL (at
      initial diagnosis) and 38 lymph nodes involved by RLH were subjected to a battery
      of 3-color combinations of well-characterized fluorochrome-conjugated monoclonal
      antibodies (DAKO) to a number of lymphocyte subsets. Cells were analyzed on a
      FACSCalibur flow cytometer with CellQuest software (Becton Dickinson). RESULTS:
      Overall, CD4+ T cells are increased and CD19+ B cells decreased in HL vs. RLH,
      yielding median T:B cell (CD3:CD20) ratios of 2.3:1 and 1.6:1, resp. There is no
      difference in median CD8+ T cell % (16% in HL & RLH). The T:B cell ratio is
      highest in nodular sclerosis (NSHL) and lymphocyte depletion (LDHL) subtypes, and
      lowest in mixed cellularity HL (MCHL). There is no significant difference in
      CD4:CD8 ratio in any comparison. NKT cells were slightly increased in HL vs. RLH,
      especially in MCHL. CD4+CD25+ regulatory T cells are significantly increased in
      HL (9%) vs. RLH (2%), especially in MCHL (29%) and NSHL (12%). EBV positivity in
      NSHL is associated with older age, decreased CD4+CD25+ regulatory T cells,
      CD4:CD8 ratio, and CD19/CD20+ B cells, and increased NKT cells, and CD14+ low
      forward-side scatter-gated monocytes. CONCLUSION: The cellular composition of the
      reactive lymphocytic infiltrate in HL differs significantly from that seen in
      RLH, with significant differences also noted between HL subtypes. In general, the
      HL infiltrate contains increased T cells (CD4+ and NKT subsets), decreased B
      cells, and increased regulatory T cells in comparison with RLH. The major
      difference between HL subtypes is decreased CD4+ T cells in MCHL as compared with
      NSHL and NLPHL. The most notable EBV-related difference in NSHL is increased
      regulatory T cells in EBV negative cases. While many differences in the reactive
      lymphocytic infiltrate of Hodgkin lymphoma and reactive lymphoid hyperplasia were
      identified, the sole difference that may prove to be of differential diagnostic
      value in flow cytometric analysis of HL versus RLH is the increased percentage of
      CD4+ bright CD25+ regulatory T cells in HL.

PMID- 18061946
TI  - Positive selection for CD90 as a purging option in acute myeloid leukemia stem
      cell transplants.
AB  - BACKGROUND: Several studies showed the benefit of purging of acute myeloid
      leukemia (AML) stem cell transplants. We reported previously that purging by
      positive selection of CD34+ and CD133+ cells resulted in a 3-4 log tumor cell
      reduction (TCR) in CD34- and/or CD133- AML, but has been shown to be potentially
      applicable in only about 50% of cases. Similar to CD34 and CD133, CD90 marks the
      hematopoietic CD34 positive stem cells capable of full hematopoietic recovery
      after myeloablative chemotherapy, and therefore, in the present study, we
      explored whether a similar purging approach is possible using CD90. METHODS: CD90
      expression was established by flowcytometry in diagnosis AML on the clonogenic
      AML CD34+ blast population by flow cytometry. Positivity was defined as >3% CD90
      (CD34+) expression on blasts. For the calculation of the efficacy of TCR by
      positive selection, AML blasts were recognized by either prelabeling diagnosis
      blasts with CD45-FITC in spiking model experiments or using expression of
      leukemia associated marker combinations both in spiking experiments and in real
      transplants. RESULTS: In 119 patients with AML and myelodysplastic syndrome, we
      found coexpression of CD34 and CD90 (>3%) in 42 cases (35%). In AML patients 60
      years or younger, representing the patients who are eligible for transplantation,
      only 23% (16/69) of the patients showed CD90 expression. Positive selection for
      CD90 in transplants containing CD90 negative AML resulted in a 2.8-4 log TCR in
      the models used. CONCLUSIONS: Purging by positive selection using CD90 can
      potentially be applied effectively in the majority of AML patients 60 years or
      younger.

PMID- 18061947
TI  - Multiparametric analysis of normal and postchemotherapy bone marrow: Implication
      for the detection of leukemia-associated immunophenotypes.
AB  - BACKGROUND: The knowledge of normal marrow is mandatory to assess the malignant
      counterpart of normal cells and define leukemia-associated immunophenotypes
      (LAIPs). In this study, the expression of a variety of antigens expressed in
      normal and postchemotherapy bone marrow (BM) was analyzed to provide a frame of
      reference for the identification of myeloid LAIPs. METHODS: Multiparameter four-
      and six-color flow cytometry was used to define antigen combinations totally
      absent or present at very minimal levels in marrow cells of normal individuals (n
      = 20) and patients receiving chemotherapy for acute lymphoblastic leukemia (n =
      20). Immature (blast) cells were gated according to CD45/SSC properties. Fifty
      three acute myeloid leukemia (AML) samples were studied in six-color
      combinations. RESULTS: In six-color flow cytometry, 47 phenotypes were totally
      absent from blast gate in all normal samples. Forty-one other phenotypes were
      identified in less than 0.05% of blast cells. There was no difference between
      normal and postchemotherapy BMs. The four-color panel allowed to identify only 30
      phenotypes present at a frequency <0.05%. Using the six-color panel, 58% of the
      absent or infrequent phenotypes in normal BM were found in at least one of 53 AML
      samples. All AML cases exhibited at least one LAIP. CONCLUSION: Our results show
      that the ability to distinguish leukemic from healthy cells is considerably
      increased by a six-color approach. Furthermore, these absent or infrequent
      phenotypes in normal BM are identified in AML and can be utilized for minimal
      residual disease study.

PMID- 18061948
TI  - Flow cytometric assessment of platelet aspirin resistance using light scattering.
AB  - BACKGROUND: A simple and reliable assay is needed for the prediction of the
      clinical efficacy of antiplatelet aspirin therapy. We have devised another method
      for the evaluation of platelet function and aspirin resistance (AR), via
      conventional flow cytometry (FCM). METHODS: To devise an optimized protocol for
      the assessment of platelet AR, various analytic variables of FCM were
      investigated. Using this devised protocol, AR was assessed in healthy subjects as
      an example. RESULTS: The protocol utilized herein is as follows: citrate
      anticoagulated platelet-rich plasma was mixed 1:1 with HEPES-buffered saline in
      two tubes, one of which is treated with aspirin. During the acquisition of FCM,
      arachidonate is added to the tube. The response of the aspirin-treated platelets
      is then compared with those of nontreated ones on a time/forward scatter plot. In
      the 61 total subjects, none was identified as aspirin resistant by this assay.
      CONCLUSIONS: Using light scattering, platelet aggregation and aspirin's
      antiplatelet effects can be readily and cost-effectively detected. According to
      this assay, biochemical AR appears to be rare. This new protocol may prove useful
      in a clinical setting or as a research tool.

PMID- 18061949
TI  - CD158k/KIR3DL2 is a useful marker for identifying neoplastic T-cells in Sezary
      syndrome by flow cytometry.
AB  - Enumeration of neoplastic T-cells in peripheral blood specimens is necessary for
      the diagnosis of Sezary syndrome (SS) and monitoring treatment responses. Because
      neoplastic T-cells in SS can be difficult to identify by morphology alone, flow
      cytometry immunophenotyping is often utilized. However, the reported
      immunophenotypic criteria for identifying neoplastic T-cells in SS are variable,
      not present in all cases, or sometimes found in reactive T-cell populations.
      Peripheral blood lymphocytes from 33 cases of SS were evaluated for the
      expression of pan-T cell antigens and killer cell immunoglobulin-like MHC
      receptors (KIR) CD158a, CD158b, CD158e, CD158i, and CD158k by multiparameter flow
      cytometry using monoclonal antibodies EB6, GL183, FES172, Z27, and Q66. A variety
      of abnormalities related to expression of pan-T-cell antigens typical of
      neoplastic T-cells were observed. Expression of CD158k was observed in 32/33
      cases and restricted to the phenotypically abnormal T-cell populations, while
      expression of other KIR was mostly negative. Our findings confirm and extend
      recent reports by one group that CD158k is expressed by most SS cases. Moreover,
      our observation that CD4 positive, CD7 negative T-cells are mostly CD158k
      negative further suggests that CD158k may be able to help identify and enumerate
      neoplastic T-cells in SS even when present at low levels.

PMID- 18061950
TI  - The role of flow cytometry in the interferon-gamma-based diagnosis of active
      tuberculosis and its coinfection with HIV-1--A technically oriented review.
AB  - TB remains uncontrolled. In resource-rich countries, only approximately 60% of
      diagnoses are confirmed by culture. The number is lower in resource-poor
      environments. Huge scope therefore exists for alternative diagnostic strategies.
      Counting antigen-specific lymphocytes by virtue of cytokine production following
      8-16 h stimulation with tuberculosis antigens is currently the strategy of
      choice. Several methods exist, including ELISA, ELISpots, and flow cytometry.
      Although it is clear that blood samples stimulated by ESAT-6 and CFP-10 antigens
      discriminate between TB infection and BCG vaccination, it is flow-cytometry that
      seems to be able to distinguish active TB disease from mere TB exposure. Of the
      various flow-protocols including four-color tests (CD45-CD3-CD4-IFNgamma), three
      color tests (CD3-CD4-IFNgamma) and two-color tests (CD4-IFNgamma), even the
      simplest is performing well, provided that the results are expressed as
      percentage of IFN-gamma+ cells per CD4+ lymphocytes (%IFNgamma/CD4+). Studies
      using broncho-alveloar lavage (BAL) and Induced-Sputum (ISp) show that TB
      specific CD4+IFN-gamma+ T cells accumulate in the lung in pulmonary and extra
      pulmonary TB at frequencies >5-20-fold more frequent than in blood. This
      pulmonary homing is absent following BCG immunization. The use of PPD to
      stimulate CD4+IFN-gamma+ cells in the lung in active TB leads to >3-12-fold
      greater responses than seen with CFP-10 or ESAT-6, and any interference from BCG
      vaccination is absent. This method is unaffected by HIV coinfection, which has
      always been the problem for other immune-based diagnostics. Further, lung-based
      samples provide material for rapid tests of both the IFN-gamma assay and
      bacteriology, and importantly, these tests are amenable for future simplification
      with automated fluorescence-image cytometers.Another development of the
      multiparameter analytical power of flow-cytometry is to use markers for "lung
      seeking" populations of CD4+ T cells in blood, obviating lung sampling. In active
      TB, but not in BCG vaccinees, TB-specific memory CD4+ T cells can be found in
      blood that are dominantly CD27-negative and probably lung seeking and can be
      diagnostically useful.

PMID- 18061951
TI  - Impact of trisomy 12, del(13q), del(17p), and del(11q) on the immunophenotype,
      DNA ploidy status, and proliferative rate of leukemic B-cells in chronic
      lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is a well-defined clinical entity
      with heterogeneous molecular and cytogenetic features. Here, we analyze the
      impact of trisomy 12, del(13q), del(17p), and del(11q) as determined by
      interphase fluorescence in situ hybridization analysis of purified neoplastic B
      CLL cells on their immunophenotype, DNA ploidy status and proliferative
      rate.Overall, 111 of 180 (62%) B-CLL cases studied displayed one (50%) or more
      (12%) genetic abnormalities, del(13q) (35%) being more frequently detected than
      trisomy 12 (23%) followed by del(11q) (9%) and del(17p) (8%). Trisomy 12 was
      associated with a higher frequency of DNA aneuploidy, stronger expression of
      CD19, CD20, CD22, CD24, CD27, CD79b, CD38, and sIg and lower reactivity for CD43
      with respect to cytogenetically nonaltered cases. In turn, cases with del(13q)
      displayed greater reactivity for CD20, FMC7, CD27, CD22, CD5, and bcl2, while
      del(11q) was associated with brighter expression of CD38, FMC7, CD25, and sIg.
      Hierarchical clustering analysis of the immunophenotype of B-CLL cases with
      cytogenetic abnormalities allowed the identification of three different groups of
      patients with increasing frequencies of trisomy 12, del(11q), and del(13q).
      Remarkably, none of the cytogenetic abnormalities analyzed except coexistence of
      13q- and 17p- had a clear impact on the proliferative index of B-CLL cells.

PMID- 18061953
TI  - Clinical applications and availability of CD4+ T cell count testing in sub
      Saharan Africa.
AB  - The absolute CD4+ T cell count in adults and CD4+ T cell percentage of
      lymphocytes (CD4%) in pediatrics compliment clinical history and physical
      examination to inform decisions about initiating antiretroviral therapy (ART). In
      addition, these immunologic markers predict host susceptibility to specific
      opportunistic infections, selected drug toxicities, and mortality. These benefits
      argue strongly for the availability of CD4+ T cell testing capacity in all
      settings where HIV infection is treated. Several currently available flow
      cytometry-based devices, and novel CD4+ T cell enumeration techniques such as the
      panleucogating CD4 are especially suitable for resource-constrained settings. At
      this time, unfortunately, the landscape of HIV care in sub-Saharan Africa is a
      mosaic characterized by large areas where CD4+ T cell testing capacity is limited
      or unavailable, and small, but growing, pockets where the capacity exists.
      Routine HIV quantification is currently unaffordable and unsustainable in the
      great majority of the region; therefore, a reliance on CD4+ T cell testing is
      inevitable for now. To this end, correcting the disparities in CD4+ T cell
      testing capacity and defining the minimum laboratory requirements for the safe
      use of antiretroviral drugs through well-designed clinical studies are some of
      the most urgent priorities of the ongoing global scale-up of ART.

PMID- 18061952
TI  - Total nucleated cell differential for blood and bone marrow using a single tube
      in a five-color flow cytometer.
AB  - BACKGROUND: Flow cytometry allows the use of several antibodies in addition to
      light scatter, and most flow cytometers will provide at least seven measurements
      on each cell passing through the laser beam. A skilled microscopist will classify
      at least 14 cell classes in bone marrow or blood. Our goal was to use the seven
      parameters available in our flow cytometer to provide a reliable differential
      count using only one tube. METHODS: Peripheral blood samples were analyzed on the
      Beckman Coulter LH750 cell counter, and the flagging and messages from the cell
      counter were used to select normal or pathological samples. Samples without flags
      (N = 50), with >2% erythroblasts (N = 80), or with "Blast" or "Verify diff" flags
      (N = 54) were investigated. We used a lyse-no-wash method to ensure minimal loss
      of fragile cells with live gating on DRAQ5-positive cells to acquire only
      nucleated cells. The FL-1 to FL-4 channels were used for the antibodies CD36
      FITC, CD203-PE, CD138-PE, CD45-ECD, CD16-Pcy5, and CD56-Pcy5. FL-5 was used for
      the DNA-stain DRAQ5. RESULTS: Using live gate acquisition on DRAQ5, we were able
      to classify total nucleated cells into 10 classes. We were unable to identify
      megakaryocytes, but platelets could be studied by rerunning the sample after
      dilution and gating on DRAQ5-negative CD36-posive events. Validation against
      digitized microscopy and cell counter showed linear correlations within each cell
      class with correlation coefficients that seem reasonable for cellular
      classification. The lowest correlation was found for basophil granulocytes. Flow
      cytometry detected twice as many immature neutrophils compared to microscopy.
      CONCLUSIONS: We have designed a one-tube immunophenotyping panel for
      classification of total nucleated cells and platelets in blood or bone marrow.
      The seven parameters available in one single tube in our cytometer seem to be
      enough for reliable differential count even in difficult pathological samples.
      The analytical imprecision of the flow cytometer differential was much lower than
      that obtained with microscopy or cell counter differentials.

PMID- 18061954
TI  - Unusual direct phycoerythrin labeling of B-cells from a splenic marginal zone
      lymphoma.
AB  - Flow cytometry is the most widely used method for lymphocyte subset
      characterization. Two types of antibodies, directly labeled with fluorochrome,
      are currently used for immunological diagnosis of B-cell lymphoproliferation:
      monoclonal antibodies against leukocyte differentiation antigens and polyclonal
      antibodies against immunoglobulins and light chains. In this study is described
      the case of a patient with an uncommon immunophenotyping of a B-cell
      lymphoproliferative disorder. B-cells from peripheral blood and from bone marrow
      reacted positively with all the tested phycoerythrin (PE)-conjugated antibodies,
      including the isotypic control. So we thought about a B-cell proliferation
      carrying a surface receptor recognizing PE: these B-cells were directly labeled
      with streptavidin-PE, indeed. Moreover, the immunodots from the patient were able
      to fix the streptavidin-PE. Finally, this unusual immunophenotyping was solved by
      using antibodies labeled with other fluorochromes than PE.

PMID- 18061955
TI  - Low-cost enumeration of CD4+ T cells using a density-based negative selection
      method (RosetteSep) for the monitoring of HIV-infected individuals in non-OECD
      countries.
AB  - The CD4 count is the best surrogate marker for monitoring HIV. The reference
      method for assessing CD4 counts (flow cytometry, FCM), as expensive technique, is
      not widely used in non-OECD countries. To make HIV-monitoring available to more
      patients in these countries, we modified a commercially available density-based
      negative selection assay (RosetteSep) to make it applicable for low-cost cell
      enumeration. For evaluation (Step 1), blood taken from 25 HIV patients and 29
      healthy donors was assayed with the modified negative selection method (MNS) and
      compared with FCM. For validation (Step 2), this method was performed in blind
      quintuplicates on 12 HIV+ blood samples according to FDA guidelines. Association
      of MNS with the FCM is given by regression models for both steps: Step 1: slope =
      1.091, intercept = -46.5. Step 2: slope = 1.074, intercept = -38.3 (Step 2). The
      imprecision of MNS assessed during Step 2 was 21.2% (intraserial) and 18.8%
      (interserial). The results suggest that MNS is capable of providing an
      approximate CD4 count. At a cost of 0.30, it is affordable to patients living in
      resource-restrained areas. The technique has the potential to deliver an
      accurate, precise, low-cost test to monitor HIV+ patients.

PMID- 18061956
TI  - Cytomics reaches microbiology-population heterogeneity on the protein level
      caused by chemical stress.

PMID- 18061957
TI  - Three-dimensional distribution patterns of CD34 antigen on nonactivated cord
      blood cells.
AB  - Circulating immature blood cells are inhomogeneous in most cytometric parameters,
      including CD34 expression. This surface antigen forms patches, and we studied
      their spatial distribution pattern by processing staggered and digitalized
      microscopical images; the number, fluorescence intensity, and volume were
      determined in randomly identified CD34-positive cord blood cells in suspension.
      Quantitative fluorescence analysis of individual CD34-labeled cells was performed
      after acquisition of microscopical images in high resolution by using a CCD
      camera and adjacent deconvolution. Two major (n = 42 and n = 41) and one minor (n
      = 5) group of haematopoietic progenitors with different CD34+ distribution
      patterns were detected. All CD34 antigen patches are localized on the spherical
      cell membrane, and differ most significantly in fluorescence intensity (P < 10(
      4)), antigen volume (P < 0.004), and patch number per cell (P < 0.02). If all
      parameters are employed, 96.6% of CD34+ cells are correctly classified into one
      of the three groups as shown by discriminant analysis. If fluorescence intensity
      is eliminated, recognition efficiency decreases to 68.2%, indicating that this is
      the most powerful single parameter. While total fluorescence intensity is most
      characteristic for each group, total patch volume and number per cell, and
      heterogeneity of patch volumes and their spatial distribution also contribute
      significantly to reliable classification into their groups.

PMID- 18061958
TI  - Bilateral changes in neuronal activity of the basal ganglia in the unilateral 6
      hydroxydopamine rat model.
AB  - The functional significance of the interhemispheric projections on the basal
      ganglia level is poorly understood. Insofar as the anatomical evidence for
      crossing projections between basal ganglia nuclei is sparse, whereas tracing
      studies demonstrated important crossing projections from the pedunculopontine
      nucleus (PPN) to the basal ganglia, it is suggested that the PPN might play a key
      role in interhemispheric regulation of basal ganglia activity. The present study
      was performed to assess changes in neuronal activity of ipsilateral and
      contralateral subthalamic nucleus (STN), substantia nigra pars reticulata (SNr),
      and PPN in the unilateral 6-hydroxydopamine (6-OHDA) rat model of advanced PD
      under urethane anesthesia. After unilateral lesioning of the SNc, the firing rate
      of contralateral STN neurons significantly increased from 10.9 +/- 1.0 spikes/sec
      (mean +/- SEM) to 16.3 +/- 1.5 spikes/sec. Similarly, the firing rate of
      contralateral SNr neurons significantly increased from 19.4 +/- 1.2 to 25.7 +/-
      1.9 spikes/sec, and the firing rate of contralateral PPN neurons significantly
      increased from 10.6 +/- 0.8 to 13.9 +/- 1.1 spikes/sec. The observed activity
      changes in contralateral STN, SNr, and PPN are similar to those induced in the
      corresponding nuclei of the hemisphere ipsilateral to the nigrostriatal
      degeneration. Based on previous, predominantly anatomical data, the results of
      the present study suggest that the PPN on the lesioned side is at the origin of
      changes in the activity of STN and SNr on the contralateral hemisphere, because
      of its crossing efferent projections.

PMID- 18061959
TI  - A correlation study of immunophenotypic, cytogenetic, and clinical features of
      180 AML patients in China.
AB  - New WHO classification has been widely applied in the diagnosis of leukemia. To
      elucidate the immunophenotype of acute myeloid leukemia (AML) and characterize
      the correlation among morphological, immunological, cytogenetic, and clinical
      features, we studied the bone marrow immunophenotypes of 180 AML patients in
      China by flow cytometry. The results showed that CD34, CD2, CD14, CD19, CD56, and
      HLA-DR were correlated with FAB subtypes. Amongst the 180 patients enrolled in
      this study, 122 cases were also subjected to karyotype analysis by G-banding
      technology and abnormal karyotypes were detected in 69 out of 122 patients.
      Correlation assay showed that t(8;21) was only present in 16 AML-M2 patients, and
      strongly associated with the individual or combinational expressions of
      CD15/CD19/CD34/CD56. As to M3, although lymphoid lineage antigens were observed
      in a considerable number of patients, they were never detected in t(15;17)
      positive patients. The expressions of CD22, CD56, and TdT showed significant
      correlation with the overall presence of abnormal karyotype. Additionally, the
      expressions of CD4, CD7, CD14, CD56, and TdT were positively correlated with
      clinical features such as white blood cell count, platelet count, and patient's
      age. In conclusion, immunophenotype analysis was useful for AML diagnosis and
      classification. At the same time, the data also suggested that the karyotype
      abnormalities and clinical features were tightly linked with abnormal antigen
      expression characteristics in AML patients. As one of the largest correlative
      study performed in China, the results highlighted the importance of a
      morphological, immunological, and cytogenetic classification of AML that might
      constitute a working basis for future studies aimed at a better definition of
      clinicopathological features and optimal treatment strategy for these leukemias.

PMID- 18061960
TI  - Deficient lower-segment Cesarean section scars: prevalence and risk factors.
AB  - OBJECTIVE: To examine the sonographic features of transverse lower-segment
      uterine Cesarean section scars in non-pregnant, premenopausal women and to
      identify factors associated with scar deficiency. METHODS: Non-pregnant,
      premenopausal women with histories of previous transverse lower-segment Cesarean
      sections, who were referred for an ultrasound scan for a variety of gynecological
      indications, were included in this study. An attempt was made to identify the
      uterine scars on transvaginal ultrasound scan and to describe their locations and
      morphological features. Various demographic, clinical and ultrasound data were
      examined in order to identify factors associated with deficient scars. Deficient
      scars were defined as detectable myometrial thinning at the site of the Cesarean
      section scar. RESULTS: Lower-segment uterine scars were detected in 321/324
      (99.1%; 95% CI, 98.0-100) women with a history of previous Cesarean section.
      Sixty-three (19.4%; 95% CI, 15.1-23.8) women had evidence of deficient Cesarean
      scars. Using multivariate analysis, a history of multiple Cesarean sections,
      uterine retroflexion and the inability to visualize all Cesarean scars in women
      with previous multiple Cesarean sections were all shown to be significantly
      associated with deficient scars. CONCLUSION: Deficient uterine scars are a
      frequent finding in women with a history of previous Cesarean section. The risk
      of scar deficiency is increased in women with a retroflexed uterus and in those
      who have undergone multiple Cesarean sections.

PMID- 18061961
TI  - Exploring quality of life for eating-disordered patients.
AB  - This qualitative study used a semi-structured interview to explore whether user
      perspective on quality of life changed following a 12 week day therapy programme
      for eating disorders. Thematic analysis was used to explore emergent themes. The
      most significant finding was the difference between the trajectories of the
      completers and the non-completers of the day programme. Whilst completers and non
      completers were similar at the start of the programme, completers moved through
      aspiration to actual change in the quality of their lives, whereas non-completers
      were unable to take their aspiration through to action. One possible explanation
      for the findings is that motivation may be an important intermediate variable,
      with completers of the programme being more motivated to improve not only their
      symptoms but also the quality of their lives more generally.

PMID- 18061962
TI  - Emotional awareness and core beliefs among women with eating disorders.
AB  - Patients with eating disorders have been shown to experience the emotional
      components of alexithymia-difficulties in identifying and describing emotions. In
      keeping with cognitive theories, which stress the role of schema-level beliefs in
      understanding emotions, this study examined the core beliefs that are associated
      with this difficulty in women with eating disorders. Seventy eating-disordered
      women completed standardised measures of core beliefs and alexithymia. There were
      no differences in alexithymia between diagnostic groups, so the women were
      treated as a single, transdiagnostic group. Multiple regression analyses showed
      specific patterns of association between the core beliefs and the emotional
      elements of alexithymia. Difficulties in identifying emotions were associated
      with entitlement beliefs, while difficulties in describing emotions were
      associated with both abandonment and emotional inhibition beliefs. These findings
      suggest that it may be necessary to work with core beliefs in order to reduce
      levels of alexithymia, prior to addressing the emotions that drive and maintain
      pathological eating behaviours.

PMID- 18061963
TI  - Longterm treatment benefits are best reflected by patient reported outcomes.

PMID- 18061964
TI  - Physician... Attorney of the poor.

PMID- 18061965
TI  - Venous thromboembolism in Wegener's granulomatosis.

PMID- 18061966
TI  - Does red-man reaction stimulate macrophage activation syndrome in children with
      systemic juvenile idiopathic arthritis?
AB  - Macrophage activation syndrome (MAS) is a major cause of death in patients with
      systemic juvenile idiopathic arthritis (JIA). We describe 4 patients who
      developed MAS during or after vancomycin treatment. Vancomycin should be used
      with great care in patients with systemic JIA.

PMID- 18061967
TI  - Sarcoidosis-like reaction related to Propionibacterium acnes and immune
      restoration syndrome in HIV infection .
AB  - Propionibacterium acnes is thought to be a potential triggering agent of
      sarcoidosis. We describe a woman who developed chronic meningitis with sarcoid
      like multisystemic involvement under treatment for human immunodeficiency virus
      infection. P. acnes was isolated from cerebrospinal fluid. We assume that P.
      acnes might have triggered this sarcoid-like reaction with meningitis, as a
      consequence of an immune reconstitution.

PMID- 18061968
TI  - Whole-body magnetic resonance imaging evaluation of widespread inflammatory
      lesions in a patient with ankylosing spondylitis before and after 1 year of
      treatment with infliximab.

PMID- 18061969
TI  - Chronic recurrent multifocal osteomyelitis.

PMID- 18061970
TI  - Pseudospondylitis caused by rupture of an aortic aneurysm.

PMID- 18061971
TI  - Systemic lupus erythematosus in a patient treated with etanercept for
      polyarticular juvenile rheumatoid arthritis.

PMID- 18061972
TI  - Central nervous system involvement in Blau syndrome: a new feature of the
      syndrome?

PMID- 18061973
TI  - Diagnosis of Muckle-Wells syndrome - 33 years later.

PMID- 18061974
TI  - MEFV mutations in patients with familial Mediterranean fever in the Black Sea
      region of Turkey: Samsun experience [corrected].
AB  - OBJECTIVE: To investigate MEFV mutations among patients with familial
      Mediterranean fever (FMF), their relatives, and healthy controls in the Black Sea
      region of Turkey; to compare 3 different MEFV mutation analysis methods; to
      evaluate the role of MEFV mutations in the diagnosis of FMF; and to investigate
      the role of M694V in the development of amyloidosis. METHODS: In total, 890
      subjects (625 patients, 165 relatives, 100 healthy controls) were included in
      this prospective study. MEFV mutations were studied with the amplification
      refractory mutation system (ARMS; n = 335), polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP; n = 335), and reverse hybridization assay
      (FMF StripAssay; n = 693). RESULTS: All methods were used in 79 patients. The
      ratio of false negativity was about 2% using ARMS compared to PCR-RFLP. The FMF
      StripAssay was used to investigate 9 more mutations and detected 17 mutations in
      14 patients. The M694V/M694V genotype was more common in patients with
      amyloidosis (37%) compared to patients without amyloidosis (18%) (p = 0.009). The
      frequency of MEFV carriers was 27%. The frequency of individuals having 2
      mutations among asymptomatic relatives of FMF patients was 6%. CONCLUSION: The
      FMF StripAssay is a reliable and time-saving method. In spite of detection of new
      mutations and developments in MEFV assay technology, there were patients in whom
      no mutation was detected. Our data, combined with previous studies, show that
      patients having M694V/M694V carry a risk for amyloidosis.

PMID- 18061975
TI  - Regulation of tenascin-C expression by tumor necrosis factor-alpha in cultured
      human osteoarthritis chondrocytes.
AB  - Expression of tenascin-C reappears in articular cartilage of persons with
      osteoarthritis (OA), while it is almost abolished in normal mature cartilage.
      Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, is
      upregulated in OA cartilage and is involved in the progression of OA, and
      stimulates tenascin-C expression in other types of cells. We investigated
      regulation of tenascin-C expression by TNF-alpha through nuclear factor-alphaB
      (NF-kappaB) in OA cartilage in vivo and in vitro. METHODS: Human articular
      cartilages were obtained from patients with OA and immunofluorescence examination
      of tenascin-C and the activated RelA subunit was performed. Cultured chondrocytes
      isolated from human OA cartilage were treated with TNF-alpha and with SN50.
      Activation of RelA subunit of NF-kappaB was examined by immunolabeling. Changes
      in tenascin-C protein concentrations were determined by immunofluorescence of
      cells after monensin treatment and Western blot analysis of the cell lysates, and
      mRNA levels were analyzed by quantitative real-time polymerase chain reaction.
      RESULTS: Increased intensity of tenascin-C staining was observed in the damaged
      cartilage compared with normal cartilage. Activated RelA staining in chondrocyte
      nuclei was prominent in tenascin-C-positive areas of OA cartilage. Treatment of
      cultured chondrocytes by TNF-alpha induced translocation of activated RelA to the
      nuclei, followed by upregulation of tenascin-C expression in both mRNA and
      protein. Treatment with SN50 inhibited increases of RelA and tenascin-C
      expression in chondrocytes. CONCLUSION: TNF-alpha stimulated tenascin-C
      expression through NF-kappaB signaling with RelA activation in cultured OA
      chondrocytes, suggesting involvement of tenascin-C in OA cartilage remodeling.

PMID- 18061976
TI  - The hand arthropathy of hereditary hemochromatosis is strongly associated with
      iron overload.
AB  - OBJECTIVE: To analyze the clinical characteristics and genetic background
      associated with the presence of hand arthropathy, as determined by radiological
      findings, in Italian patients with hereditary hemochromatosis (HHC). METHODS: In
      88 consecutive unselected patients with phenotypically expressed HHC, joint
      involvement was systematically evaluated in plain radiographs of hands, wrists,
      lumbar spine, pelvis, and knees. Risk factors considered were age, sex, body mass
      index, alcohol abuse, organ involvement at other sites, and indices of iron
      overload, including ferritin, transferrin saturation, and iron removed to reach
      depletion. HFE genotype was also considered. The independent role of risk factors
      was tested by logistic regression analysis. RESULTS: Thirty-two subjects (36%)
      showed signs of metacarpophalangeal (MCP) arthropathy. Intercarpal, radiocarpal,
      and chondrocalcinosis were less frequent and occurred in association with MCP
      arthropathy. At multivariate analysis MCP arthropathy was independently
      associated with older age [odds ratio (OR) 1.20, 95% confidence interval (CI) 1.1
      1.33/yr; p = 0.0001], higher ferritin levels at diagnosis (OR 4.17, 95% CI 1.60
      13.9 for values > 1000 ng/ml; p = 0.008), the presence of the C282Y +/+ and
      C282Y/H63D HFE genotypes (OR 2.69, 95% CI 1.09-7.87; p = 0.04), and higher
      percentage transferrin saturation (OR 1.05, 95% CI 1-1.1; p = 0.05). The severity
      of arthropathy was independently associated with older age (p = 0.03) and higher
      ferritin values (p = 0.05). CONCLUSION: MCP arthropathy together with a typical
      pattern of joint involvement is observed in one-third of unselected patients with
      HHC, and is influenced by the duration and degree of the iron overload.

PMID- 18061977
TI  - Trends in drug prescribing for osteoporosis after hip fracture, 1995-2004.
AB  - OBJECTIVE: To examine trends in osteoporosis drug prescribing after hip fracture
      from 1995 to 2004. METHODS: We conducted a population-based study of enrollees in
      the Pennsylvania Pharmaceutical Assistance Contract for the Elderly. Hip
      fractures were identified using Medicare hospital claims between January 1, 1995,
      and June 30, 2004. Osteoporosis treatment comprised oral bisphosphonates,
      calcitonin, hormone therapy, raloxifene, and/or teriparatide. Kaplan-Meier
      methods were used to estimate the probability of treatment within 6 months of
      fracture, censoring patients on their date of death or 6 months postfracture.
      RESULTS: Treatment within 6 months after hip fracture improved from 7% in 1995 to
      31% in 2002, and then remained stable through 2004. Similar patterns were
      observed among new users, with treatment increasing from 4% in 1995 to 17% in
      2002, with no subsequent increase through 2004. Bisphosphonates led other
      treatments in the frequency of prescribing, except during 1997-99, when
      calcitonin was the most common. Among women, hormone therapy prescribing
      decreased from 22% of those treated in 1995 to 4% in 2004, and raloxifene
      prescribing remained relatively constant (4%-10%) since its introduction (p for
      trend = 0.15). Of patients treated before and after hip fracture, 18% changed
      therapy postfracture. Significantly more patients changed therapy following
      fracture if a different physician prescribed treatment (26%) compared to those
      treated by the same physician pre- and postfracture (13%; p < 0.0001).
      CONCLUSION: Prescribing practices changed substantially over the 10 years of
      study. The proportion of hip fracture patients treated with osteoporosis drugs
      has increased, but remains low, with fewer than one-third receiving
      pharmacotherapy.

PMID- 18061978
TI  - Elevated parathyroid hormone 44-68 in idiopathic calcium pyrophosphate dihydrate
      crystal deposition disease. Role of menopause and iron metabolism?
AB  - OBJECTIVE: To examine whether idiopathic calcium pyrophosphate dihydrate (CPPD)
      crystal deposition disease (CDD) is related to altered parathyroid hormone (PTH)
      metabolism. METHODS: Forty-two patients with idiopathic CPPD CDD were compared
      with 67 controls, 33 of whom were matched for age and sex. RESULTS: Serum PTH 44
      68 concentrations were elevated in 29% of patients and were significantly higher
      in the patients than in their sex- and age-matched controls (Z = -4.664, p <
      0.0001). PTH 1-84 levels were normal. Serum calcium, phosphorus, and ferritin
      levels were normal, but were significantly higher in the patients. Serum PTH 44
      68 levels correlated negatively with serum transferrin in female controls aged
      >or= 45 years, and with transferrin saturation in the female patients.
      Correlation between serum ferritin and age was linear and positive in the former
      subjects and quadratic in the latter. CONCLUSION: Elevated serum concentration of
      PTH mid-fragments containing the 44-68 region could explain the joint disorders
      associated with idiopathic CPPD CDD, as shown in genetic hemochromatosis. In
      female patients the elevation of PTH mid-fragments could be linked to changes in
      iron metabolism provoked by the menopause.

PMID- 18061979
TI  - Magnetic resonance imaging assessment of spinal inflammation in patients treated
      for ankylosing spondylitis.
AB  - OBJECTIVE: To compare different magnetic resonance imaging (MRI) based algorithms
      for assessment of spinal inflammation in patients with ankylosing spondylitis
      (AS) being treated with disease modifying drugs. METHODS: Eleven patients (10
      men, 1 woman) who fulfilled modified New York diagnostic criteria and had severe
      disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) > 4] were
      given intravenous infusion of infliximab (Remicade, 5 mg/kg) for 96 weeks. Whole
      spine MRI was done at 0, 24, and 54 weeks. Measurements of the Ankylosing
      Spondylitis Spinal MRI Activity Score (ASspiMRI), paravertebral inflammatory
      lesion count (pILC), contrast:noise ratio (CNR) measurements of defined
      inflammatory lesions, and other scores together with C-reactive protein
      concentration were made at each visit. Examinations were anonymized and randomly
      presented twice to 2 radiologists. The significance of any changes in scores,
      their correlation with the BASDAI, and interobserver and intraobserver
      correlations were calculated. RESULTS: The mean (+/- SD) BASDAI improved from 7.2
      (+/- 1.5) to 1.3 (+/- 0.9) after 54 weeks (p < 0.001), and the ASspiMRI score
      improved from 12.0 (+/- 8.0) to 0.2 (+/- 0.5) (p < 0.001). Correlations between
      ASspiMRI score and BASDAI were 0.831, 0.746, and 0.369 (p < 0.001 each). The pILC
      improved significantly (p < 0.01). CNR showed no correlation with any clinical
      score. CONCLUSION: The ASspiMRI score performed best for assessment and
      quantification of spinal inflammation and disease activity in patients with AS,
      but should also quantify paravertebral inflammatory lesions, since we could show
      that this will significantly improve its correlation to clinical scores and
      increase its sensitivity to mild inflammatory processes.

PMID- 18061980
TI  - Increased chromogranin A levels indicate sympathetic hyperactivity in patients
      with rheumatoid arthritis and systemic lupus erythematosus.
AB  - OBJECTIVE: Sympathetic hyperactivity is an unfavorable disease consequence in
      rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) due to an
      increased risk of cardiovascular events. We aimed to identify a serum marker of
      the sympathetic nervous system, the adrenal chromogranin A (CHGA), in order to
      study sympathetic hyperactivity in RA and SLE. METHODS: Serum levels of CHGA were
      measured by radioimmunoassay in healthy subjects and patients with RA and SLE.
      CHGA immunofluorescence was performed in synovium of patients with RA and
      controls with osteoarthritis (OA). CHGA levels were measured in plasma, synovial
      fluid, and synovium superfusate in RA and OA controls. RESULTS: In healthy
      subjects, systemic CHGA levels correlated positively with age and plasma
      norepinephrine, indicating the sympathetic origin (p < 0.01). Serum CHGA levels
      were higher in RA and SLE than in healthy subjects (p < 0.001), which was
      particularly evident in female patients. Immunofluorescence revealed double
      staining of CHGA and elastase-positive neutrophils in the synovium (but not with
      macrophages, T cells, fibroblasts, B cells, or tyrosine hydroxylase-positive
      cells). Density of CHGA+ cells was higher in RA synovium compared to OA controls.
      In OA controls and RA, CHGA levels were similar in plasma and synovial fluid, but
      levels in synovial tissue superfusate were markedly lower, which indicates that
      most of the CHGA is of systemic adrenal origin. CONCLUSION: Increased level of
      CHGA is a good marker of systemic sympathetic hyperactivity.

PMID- 18061981
TI  - Anti-tumor necrosis factor-alpha response in rheumatoid arthritis is associated
      with an increase in serum soluble CD30.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) display high serum
      concentrations of soluble CD30 (sCD30), which correlate with counter-regulatory
      activity of CD30+ T cells in the inflamed joint. To verify the contribution of
      this T cell subset to disease remission, sCD30 levels were analyzed
      longitudinally in patients with active RA following infliximab therapy. METHODS:
      Infliximab plus methotrexate were started in 39 patients with active RA, while 20
      patients with inactive disease, controlled by stable doses of methotrexate, acted
      as controls. Serial evaluations of sCD30 concentrations and disease activity
      indexes were performed throughout 38 weeks. RESULTS: sCD30 levels were higher in
      patients than in healthy controls. Rapid infliximab-induced decrease in disease
      activity was associated with an overall increase of sCD30 levels. In contrast,
      levels remained stable in controls. An inverse correlation between sCD30 levels
      and Disease Activity Score 28 was observed from the 22nd week of infliximab
      treatment. Analysis of sCD30 levels according to American College of Rheumatology
      response showed, after an initial general enhancement of sCD30 concentrations, a
      persistent increase of sCD30 in responders, but not in nonresponders. CONCLUSION:
      sCD30 serum levels are enhanced by tumor necrosis factor-a (TNF-a) blockade in
      patients with active RA and inversely correlated with disease activity, but only
      after some weeks of treatment. Of interest, a sustained increase of sCD30 is
      present only in subjects with evidence of persistent clinical response to anti
      TNF-alpha. As sCD30 serum levels mirror antiinflammatory activity of joint T
      cells, the present data may suggest a role of synovial counter-regulatory CD30+ T
      cells in the induction of infliximab-mediated remission in RA.

PMID- 18061982
TI  - Programmed cell death.
AB  - Programmed cell death is an integral component of C. elegans development. Genetic
      studies in C. elegans have led to the identification of more than two dozen genes
      that are important for the specification of which cells should live or die, the
      activation of the suicide program, and the dismantling and removal of dying
      cells. Molecular and biochemical studies have revealed the underlying conserved
      mechanisms that control these three phases of programmed cell death. In
      particular, an interplay of transcriptional regulatory cascades and networks
      involving CES-1, CES-2, HLH-1/HLH-2, TRA-1, and other transcriptional regulators
      is crucial in activating the expression of the key death-inducing gene egl-1 in
      cells destined to die. A protein interaction cascade involving EGL-1, CED-9, CED
      4 and CED-3 results in the activation of the key cell death protease CED-3. The
      activation of CED-3 initiates the cell disassembly process and nuclear DNA
      fragmentation, which is mediated by the release of apoptogenic mitochondrial
      factors (CPS-6 and WAH-1) and which involves multiple endo- and exo-nucleases
      such as NUC-1 and seven CRN nucleases. The recognition and removal of the dying
      cell is mediated by two partially redundant signaling pathways involving CED-1,
      CED-6 and CED-7 in one pathway and CED-2, CED-5, CED-10, CED-12 and PSR-1 in the
      other pathway. Further studies of programmed cell death in C. elegans will
      continue to advance our understanding of how programmed cell death is regulated,
      activated, and executed in multicellular organisms.

PMID- 18061983
TI  - Reply to the editorial entitled 'The European strategy on alcohol: a landmark and
      a lesson' by B. Baumberg and P. Anderson.

PMID- 18061984
TI  - Global and local conservation priorities.

PMID- 18061985
TI  - Global and local conservation priorities.

PMID- 18061986
TI  - Global and local conservation priorities.

PMID- 18061987
TI  - Development and preliminary clinical validation of a high sensitivity assay for
      cardiac troponin using a capillary flow (single molecule) fluorescence detector.

PMID- 18061988
TI  - A systematic method for selection of promising serum protein biomarkers to
      improve prostate cancer (PCa1) detection.

PMID- 18061990
TI  - Representational fragment amplification: exponential amplification of fragmented
      cDNA enables multimillion-fold expression testing.

PMID- 18061989
TI  - Bioinformatics methods for prioritizing serum biomarker candidates.

PMID- 18061991
TI  - Diffractive optics technology: a novel detection technology for immunoassays.

PMID- 18061992
TI  - Single-molecule detection for femtomolar quantification of proteins in
      heterogeneous immunoassays.

PMID- 18061993
TI  - LEAP trial.

PMID- 18061994
TI  - Prostate cancer.

PMID- 18061995
TI  - Neglected diagnostics.

PMID- 18061996
TI  - Retraction notice to "Laboratory markers associated with progression of HIV
      infection [Best Practice & Research Clinical Obstetrics & Gynaecology 19 (2005)
      243-254]".

PMID- 18061997
TI  - Words of wisdom. Re: Surveillance for recurrent bladder cancer using a point-of
      care proteomic assay.

PMID- 18061998
TI  - Words of wisdom. Re: Detection of occult nodal metastases in locally advanced
      node-negative prostate cancer.

PMID- 18061999
TI  - Paleo longevity redux.

PMID- 18062000
TI  - Words of wisdom. Re: Defining biochemical failure following radiotherapy with or
      without hormonal therapy in men with clinically localized prostate cancer:
      recommendations of the RTOG-ASTRO Phoenix Consensus Conference.

PMID- 18062001
TI  - Words of wisdom. Re: Abdominal sacrocolpopexy with Burch colposuspension to
      reduce urinary stress incontinence..

PMID- 18062003
TI  - Geriatric GERD: maximizing outcomes for a unique patient population.

PMID- 18062004
TI  - [Strength training and tai-chi to prevent accidental falls].

PMID- 18062005
TI  - [Influenza prevention for the entire practice team].

PMID- 18062006
TI  - [Symptoms in the digestive tract for diseases of other organs].
AB  - Gastrointestinal symptoms in elderly patients are not only caused by primary
      diseases of the digestive organs. Even a healthy digestive tract commensurate
      with the age of the patient is affected by age and disease-related changes of
      other organs, in particular those of the cardiovascular and metabolic systems.
      This leads to a broad spectrum of secondary dysfunctions of the gastrointestinal
      tract.

PMID- 18062007
TI  - [Field trial uncovers massive problems].

PMID- 18062009
TI  - [Using the assessment of a risk to the population's health to substantiate the
      standards for maximum permissible emission].

PMID- 18062008
TI  - [Hygienic problems of residential and public buildings].
AB  - A questionnaire survey made in different Voronezh population groups suggests that
      they spend 80 to 90% of time in the enclosed space. The greatest contribution to
      the chemical load caused by ambient air pollution made by production areas
      (54.9%) in the adult able-bodied population and by dwelling areas (56.0-86.9%) in
      children, adolescents, and pensioners. Pollution of ambient air (K = 9.19) is
      pronounced to a lesser degree than that of the air of office buildings (K =
      12.49), which suggests that there are internal contamination sources in the
      closed space. The results of the questionnaire survey of respondents suggest that
      20% suffer from allergic diseases and 7% of them associate these diseases with
      dwelling area contamination.

PMID- 18062010
TI  - [Guidelines for the assessment of regional factors of the urban populations'
      exposure].
AB  - The paper presents guidelines for assessing regional exposure factors (EFs)
      according to the results of a questionnaire survey of about two thousand persons,
      including urban workers and/or adult students of the Central Federal District
      (CFD) and Siberian Federal District (SFD) of Russia. It has been ascertained that
      in CFD, annual exposure (324 days/year) is less than the standard value defaulted
      in Guidelines P 2.1.10.1920-04 (350 days/year), which causes a reduction in the
      chronic average daily dose. Town-dwellers spend the bulk of a day indoors (86 and
      87% in CFD and SFD, respectively); 8 and 3% of a day on transport in CFD and SFD,
      and 7 and 10% indoors in these districts. The findings are in agreement with the
      data obtained by Russian and foreign investigators and suggest that the daily
      distribution of a microenvironmental load should be taken into account when
      health exposures and risks are estimated. The average daily tap water consumption
      in CFD (2.2 l/day) and SFD (1.7 l/day) is close to 90% percentile of the values
      recommended by the U.S. EPA (2.4 l/day) and the WHO or less than the value used
      in the calculation of the Russian maximum permissible concentrations for water
      (3.0 l/day). The time spent on water procedures by town-dwellers is 36.4 min/day
      in CFD and 37.6 min/day in SFD (while 29.2 min/day in rural dwellers in SFD) with
      the standard value of 30 min/day. The findings suggest that the use of the
      regional values of water-associated EFs increases the chronic average daily dose
      and therefore a risk upon oral, dermal, and inhalational exposure. The regional
      features of FEs have been kept in mind on assessing the risk upon
      multienvironmental exposures to the characteristic components of emission caused
      by aluminum works in CFD.

PMID- 18062011
TI  - [Reduction of a risk to the population's health from ambient air pollution in the
      Baikal Region: state-of-the-art and prospects].

PMID- 18062012
TI  - [Impact of short weather changes on the population's health risk from ambient air
      pollution].
AB  - The paper considers the negative impact of weather changes in combination with
      the altered quality of ambient air on the economic and social spheres of society
      and on the population's health. It describes experience in assessing a possible
      damage to the health of the Moscow population from exposure to elevated
      concentrations of ambient air pollutants (suspended matter, nitrogen and sulfur
      dioxides, carbon oxide). The results of assessment simulation of dissemination of
      chemicals contained in the emission from the Moscow heat-and-power objects under
      poor weather conditions are presented.

PMID- 18062013
TI  - [Influence of motor transport emission on children's health in Yekaterinburg].

PMID- 18062014
TI  - [Hygienic assessment of a health risk to the population of an industrial town
      from the influence of environmental factors].

PMID- 18062015
TI  - [Hygienic aspects of medical waste management in Astana].
AB  - The authors indicate the existing epidemiological risks on handling the scraps
      from the therapeutic-and-prophylactic institutions of Astana and forecast the
      volume of these waste till 2030. By analyzing the Russian experience in testing
      the technologies of medical waste disinfection, they have justified the choice of
      a thermal system to recycle Astana medical and biological wastes. The proposed
      measures to improve a waste collecting and recycling system of the city's
      therapeutic-and-prophylactic institutions are shown to be economically effective.

PMID- 18062016
TI  - [Establishing the risk of occurrence of sanitary and epidemiological consequences
      of emergencies].

PMID- 18062017
TI  - [Child's adaptation as an indicator of poor environmental influences].
AB  - The body's adjustment changes under the influence of environmental risk factors
      whose long-term exposure further results in the development of prenosological and
      morbid disorders. These processes occur most promptly in children. The influence
      of risk factors, including those caused by the productive activity of the Kotlas
      industrial CBK complex on a child's adaptation, was studied. The specific
      features revealed in the physical development, baseline autonomic tone, and
      psychophysiological adaptation of the first and tenth-form schoolchildren under
      study suggest that the mechanisms responsible for adjustment are strained under
      the influence of environmental risk factors and differ in nature, structure, and
      intensity in the exposure and comparison groups.

PMID- 18062019
TI  - [Accelerated evaluation of viral sterilized water contamination].
AB  - The paper describes an accelerated procedure for isolating enteric viruses and a
      scheme for evaluating the viral contamination of pure waters, which involves the
      concentration of the viruses from the great water volumes by means ofa MFM 0142
      membrane module with tangential filtration through an electropositive membrane
      (MMK) with a pore size of 0.2 microm, followed eluent determination of RNA of
      viruses by RT-PCR in combination with coliphages or ICC by RT-PCR.

PMID- 18062018
TI  - [A methodological scheme for examination of the urban population, by making
      multilevel assessments of exposure to ambient air pollutants].
AB  - A novel methodological design comprising multilevel assessments of exposures of
      examinees to controlled ambient air pollution according to the data of route
      stations was developed to examine the population of large towns. The design was
      tested in 4 surveys of Moscow residents (apparently healthy and outpatients with
      a number of chronic diseases). The findings indicate the fundamental possibility
      of altering the traditional differential design of biomedical surveys of the
      population, by introducing more evidence-based regression analyses and dividing
      the contributions of individual chemicals to the observed changes in health
      indices.

PMID- 18062020
TI  - [Use of a methodology for assessing a risk to the population health in the
      practice of Russian consumer surveillance bodies and organizations].

PMID- 18062021
TI  - [Development of measures to health maintenance in the programs of the
      socioeconomic developments of areas].
AB  - The paper deals with the information provision and use of mathematical
      statistical and mathematical economic methods in the substantiation of measures
      provided by the socioeconomic development programs. The development of a package
      of human health maintenance measures may involve 2 stages: (1) analysis of long
      term data on the man-caused pollution of environmental objects, socioeconomic
      conditions, and the medicodemographic situation; (2) medium-range forecast of
      indicators. Testing the proposed approaches applied in Irkutsk has ascertained
      that the investment area development causes a steady-state decrease in morbidity
      rates in all population groups and a reduction in disorders-caused economic
      damages.

PMID- 18062022
TI  - [Hygienic standards of chemicals for water sterilization in the swimming pools].
AB  - The authors proposed a concept of making the hygienic standards for water
      disinfectants in the swimming pools, by substantiating their allowable residual
      concentrations (ARC), as well as criteria for evaluating the effectiveness and
      safety of swimming pool water disinfectants: a ratio of ARC to the optimum
      bactericidal concentration (if the ratio is less than 1; the agent is not
      recommended for use); a ratio of the maximum noneffective concentration of a
      local irritant action to the optimal bactericidal concentration of a disinfectant
      (if the ratio is < or =5; the agent is not permitted for use); a specific
      activity (agents that can cause allergenic and carcinogenic effects, as well as a
      mutagenic effect revealed on mammals or man are not permitted for use); the
      content of impurities in the disinfectant (when the agent is used in the dose
      equivalent to 3-5 optimal bactericidal concentrations; the water levels of
      impurities should be not more than 0.5 of the maximum permissible concentration.
      In accordance with the proposed procedure, ARC of BioPAH
      (polyhexamethyleneguanidine hydrochloride) has been estimated to be 5 mg/l.
      However, the agent may not be permitted for use in the swimming pools as it
      contains hazardous impurities.

PMID- 18062023
TI  - [Medical rehabilitation of patients after aortocoronary bypass grafting at the
      resort with the use of combined physiotherapy].
AB  - The purpose of the work is study of efficiency of medical rehabilitation of
      patients after aortocoronary bypass grafting on the resort stage with the use of
      combined electric, electromagnetic, quantum and microvibration therapy. 150
      patients were randomized in three groups. First group (75 persons) together with
      the basic treatment (antiaggregants, beta-blockers, statins) received combined
      electric, electromagnetic, quantum and microvibration therapy. A new device
      Eliton was used. Second group (45 persons) together with the basic treatment
      received laser therapy. Third group (30 persons) received the basic treatment
      without use of physiotherapy. The patients after aortocoronary bypass grafting
      who received combined basic treatment and physiotherapy showed positive dynamics
      of functional recovery, their painful and inflammatory injuries caused by
      postoperative trauma and concomitant pathology were reducted significantly
      earlier and completely. It had a positive influence on the state of
      cardiorespiratory and vegetative nervous systems, exercise performance and
      finally on the live quality. This study confirms necessity of use of the combined
      physiotherapy in medical rehabilitation programs. Use of device Eliton makes
      possible to realize effective treatment for patients after aortocoronary bypass
      grafting.

PMID- 18062024
TI  - [Use of chloride-hydrocarbonate sodium mineral water in the combined therapy of
      cardiovascular diseases].
AB  - Ability and efficiency of use of chloride-hydrocarbonate sodium mineral water
      Karachinskaya in the combined therapy of coronary heart disease (CHD) and
      arterial hypertension (AH) were studied. Mineral water was used in regimen of
      1000 ml in a day for 10 days. This intake of mineral water did not have a
      negative influence on the course of CHD and AH. Hypocholesteremic action of the
      mineral water was registered. Probable pathogenetic mechanisms of
      hypocholesteremic action of the mineral water are analyzed. Detected effects make
      possible to recommend use of chloride-hydrocarbonate sodium mineral water
      Karachinskaya to improve health reserves and prevent cardiovascular diseases.

PMID- 18062025
TI  - [Development of intracellular structural adaptive processes during use of mineral
      waters].
AB  - Use of drinking sulphate mineral water causes development of structural adaptive
      processes in Sertoli cells of testicles, which appears in hyperplasia of various
      ultrastructures (mitochondrions, ribosomes et al.). After use of boride mineral
      water the level of development of structural adaptive reactions was lower.

PMID- 18062026
TI  - [Efficacy of the psychocorrection methods in the medical rehabilitation of
      patients with chronic salpingoophoritis and chronic pelvic pain syndrome].
AB  - Analysis of efficiency of respiratory relaxational training and of the
      visualization method was performed for 90 women with chronic salpingoophoritis
      and the syndrome of chronic pelvic pain. Use of psychocorrection made possible to
      improve efficiency of the treatment significantly decreasing intensity of the
      pain and improving psychological status of the patients. Predictors of efficiency
      and indications for differentiated use of these methods for the medical
      rehabilitation of patients were worked out.

PMID- 18062027
TI  - [Effect of the course of reflexotherapy on catecholamine, serotonin, and
      histamine levels in the rat hypothalamic structures].

PMID- 18062028
TI  - [Use of aerosol therapy with antitubercular medicines in patients with pulmonary
      tuberculosis in a mental hospital].

PMID- 18062029
TI  - [Concerning biophysical chimeras in electrotherapy (about the article
      "Biophysical characteristics of microwave therapy" by A. N. Volobuev)].

PMID- 18062030
TI  - [Nonmedicamental methods of medical rehabilitation and secondary prophylaxis of
      cardiovascular diseases].

PMID- 18062031
TI  - [DRG practice: Frequently asked questions--questions from general practice].

PMID- 18062032
TI  - [Orientation decision of established contract physicians and psychotherapists].

PMID- 18062033
TI  - [Modern surgery management is interdisciplinary, medically and economically
      responsible].

PMID- 18062034
TI  - [Damage control--the new telemedia regulation and the federal data protection law
      should effect legal clarity on the internet].

PMID- 18062035
TI  - [Organized specialty continuing enducation: old wine in new bottles or a future
      option?].

PMID- 18062036
TI  - [Methods for objective evaluation of medical management].

PMID- 18062037
TI  - [Personnel development as an important success factor for an individual
      practice].

PMID- 18062038
TI  - [Participation in national health care emergency service].

PMID- 18062039
TI  - [Comment on BDC-Chirurg Heft 4, 2007, S. 80 ff. "New specialist for orthopedics
      and trauma surgery"].

PMID- 18062040
TI  - Overexposure to antenatal corticosteroids: a global concern.

PMID- 18062042
TI  - Current awareness in phytochemical analysis.

PMID- 18062041
TI  - Cultivation of a novel cold-adapted nitrite oxidizing betaproteobacterium from
      the Siberian Arctic.
AB  - Permafrost-affected soils of the Siberian Arctic were investigated with regard to
      identification of nitrite oxidizing bacteria active at low temperature. Analysis
      of the fatty acid profiles of enrichment cultures grown at 4 degrees C, 10
      degrees C and 17 degrees C revealed a pattern that was different from that of
      known nitrite oxidizers but was similar to fatty acid profiles of
      Betaproteobacteria. Electron microscopy of two enrichment cultures grown at 10
      degrees C showed prevalent cells with a conspicuous ultrastructure. Sequence
      analysis of the 16S rRNA genes allocated the organisms to a so far uncultivated
      cluster of the Betaproteobacteria, with Gallionella ferruginea as next related
      taxonomically described organism. The results demonstrate that a novel genus of
      chemolithoautotrophic nitrite oxidizing bacteria is present in polygonal tundra
      soils and can be enriched at low temperatures up to 17 degrees C. Cloned
      sequences with high sequence similarities were previously reported from
      mesophilic habitats like activated sludge and therefore an involvement of this
      taxon in nitrite oxidation in nonarctic habitats is suggested. The presented
      culture will provide an opportunity to correlate nitrification with nonidentified
      environmental clones in moderate habitats and give insights into mechanisms of
      cold adaptation. We propose provisional classification of the novel nitrite
      oxidizing bacterium as 'Candidatus Nitrotoga arctica'.

PMID- 18062043
TI  - Spatial hearing disability after acoustic neuroma removal.
AB  - OBJECTIVES/HYPOTHESIS: Previous studies on hearing loss (HL) after acoustic
      neuroma removal concentrate mainly on pure-tone hearing results rather than
      hearing disability. Our objectives were to use the Speech, Spatial and Qualities
      of Hearing scale (SSQ), a comprehensively validated questionnaire, to
      characterize and quantify the auditory disabilities that patients experience with
      a profound unilateral HL after acoustic neuroma removal. STUDY DESIGN: Forty-four
      patients with profound unilateral HL after acoustic neuroma surgery completed the
      SSQ. Their findings were compared with those of a control population sample
      matched for age, sex, and hearing level in the better hearing ear. RESULTS: In
      comparison with controls, with use of analysis of variance, acoustic neuroma
      patients scored poorly on all items except for the identification of sounds and
      objects (P = .123). The greatest difficulties involved speech in the presence of
      noise, situations of multiple speech-streams and switching (such as listening to
      someone speaking and the television at the same time), the location of unseen
      objects, and increased listening effort (P < .05). CONCLUSION: This study
      demonstrates that, compared with a control population, these patients experience
      a significant range of auditory disabilities. It is important that clinicians be
      aware of the impact of such a profound unilateral HL and its potential to affect
      daily life. Patient counseling prior to surgery is essential, especially in
      patients whose loss of binaural hearing could constitute a major disability.

PMID- 18062044
TI  - Sterilization and wear-related failure in first- and second-generation press-fit
      condylar total knee arthroplasty.
AB  - We compared the incidence of wear-related failures between two large cohorts of
      patients undergoing total knee arthroplasty implanted with identical modular
      tibial trays and polyethylene inserts sterilized by different methods. A total of
      1183 second-generation press-fit condylar prostheses having inserts packaged and
      sterilized in an oxygen-free environment were assessed at a minimum 5-year
      followup (mean, 7.0 years). Wear-related failure was defined as (1) osteolysis
      greater than 100 mm2 or (2) revision of the implant resulting from osteolysis,
      polyethylene wear, chronic synovitis, and/or effusion. Wear-related survivorship
      was calculated using Kaplan-Meier survival analysis. Results were compared with
      our previously published study of 1287 first-generation press-fit condylar
      modular knees having inserts sterilized by gamma irradiation in air at 5-year
      minimum followup (mean, 7.8 years). The wear-related failure rate for the second
      generation design was 1.1% and 10-year survivorship was 97.0% compared with 8.3%
      failure and 87.7% 10-year survival for the first-generation design. For second
      generation components, patient age was the only variable correlated with wear
      related failure. For first-generation components sterilized in air, several
      variables were correlated to wear-related failure with shelf age of the
      polyethylene insert being the most important factor. These data emphasize the
      dramatic effect improvements in polyethylene manufacturing, specifically
      sterilization methods, can have on implant survivorship. LEVEL OF EVIDENCE: Level
      III, therapeutic study. See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 18062045
TI  - Bearing surface design changes affect contact patterns in total knee
      arthroplasty.
AB  - The impact of design changes intended to improve wear of knee replacements can be
      assessed from analysis of retrieved implants. We hypothesized changes in bearing
      surface conformity from the Insall-Burstein II knee to a successor, the Optetrak,
      intended to improve contact stresses would be apparent in wear patterns observed
      on retrieved tibial inserts. From 151 Insall-Burstein II and 54 Optetrak
      retrieved components, 35 pairs (Insall-Burstein II and Optetrak) were matched on
      length of implantation, body mass index, and age. Digital images of the bearing
      surfaces were used to identify and measure wear modes, which were then converted
      to a percentage of the total possible contact area. Burnishing was the most
      prevalent mode for both designs followed by scratching and then pitting. The
      percentage of involved area was greater for the Optetrak for 23 pairs.
      Interestingly, for the nine matched pairs with length of implantation longer than
      2 years, six of the Insall-Burstein II inserts had considerably greater
      scratching and pitting and five exhibited abrasion and creep absent from Optetrak
      implants. Bearing surface design is a major factor that can affect kinematics and
      contact patterns. Our observations confirm the considerable impact of small
      changes in conformity and suggest models predicting contact stresses adequately
      reflect in vivo performance.

PMID- 18062046
TI  - Modular insert exchange in knee arthroplasty for treatment of wear and
      osteolysis.
AB  - Wear and osteolysis have been successfully treated by modular polyethylene
      exchange in revision hip arthroplasty. However, studies of the same approach in
      revision knee arthroplasty have not provided similar results. We evaluated the
      results of isolated polyethylene exchange for wear and/or osteolysis in 68 press
      fit condylar TKAs from four centers. At a minimum of 24 months after polyethylene
      exchange surgery (average, 44 months; range, 24-83 months), there were 11
      failures (16.2%). Failures included aseptic loosening in 10 knees and infection
      in one. With the relatively small cohort size we were unable to identify factors
      that predicted which knees were more likely to fail: we observed no correlation
      between failure and patient demographics, component design, or use of cement
      versus bone graft augmentation. Radiographic review demonstrated no progression
      of osteolytic lesions in 97% of knees in the study. While the short-term followup
      limits the conclusions, we believe the 84% success rate with modular polyethylene
      exchange for wear and osteolysis and the lack of progression of osteolytic
      lesions in the majority of the knees are encouraging. Full revision of well-fixed
      total knee components can lead to substantial bone loss, particularly in the face
      of osteolysis and we therefore consider modular polyethylene exchange in press
      fit condylar knees a reasonable option for wear and osteolysis. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a
      complete description of levels of evidence

PMID- 18062047
TI  - Focused rehabilitation treatment of poorly functioning total knee arthroplasties.
AB  - Patient dissatisfaction after total knee arthroplasty (TKA) is often linked to
      complications resulting from comorbidities, radiographic loosening, and poor
      prosthetic alignment. However, some patients report functional problems without
      obvious cause. We asked if focused physical therapeutic techniques influenced the
      clinical outcome in these patients. We identified functional problems in 56
      patients after TKA and described outcomes following focused physical therapy
      modalities. Assessments included detailed physical examination, videotape
      analyses, electromyograms, nerve conduction studies, foot pressure studies, and
      isokinetic strength measurements in selected patients. Identified abnormalities
      were knee flexion contracture, quadriceps muscle weakness, knee flexion deficit,
      limb length difference, foot and ankle malalignment, and peroneal nerve
      entrapment. Focused treatment protocols for each of the six abnormalities
      included knee braces, shoe lifts, orthoses, electrical stimulation, peroneal
      nerve releases, and intramuscular botulinum toxin injections. Fifty-three
      patients (95%) had Knee Society scores greater than 80 points at final minimum
      followup of 24 months (mean, 43 months; range, 24-73 months). Patient
      satisfaction was a mean of 9.1 out of 10 possible points. Our results suggest
      focused physical therapy may help patients with difficult functional problems
      after TKA. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18062048
TI  - Revision total knee arthroplasty: the patient's perspective.
AB  - We evaluated a consecutive series of patients followed at least 1 year after
      revision total knee arthroplasty. We surveyed patients treated at three referral
      centers over 5 years. An experienced medical interviewer contacted patients and
      rated their degree of satisfaction with the original and revision arthroplasties,
      the reason for the original arthroplasty failure, and their expectations for
      revision arthroplasty longevity. Surveys were completed on 238 of the 408
      patients (58%). All patients' operative reports, clinical records, and
      radiographs were reviewed to determine the diagnosis at revision, procedure
      performed, and the most likely cause of failure. Patient satisfaction with the
      primary procedure directly related to the time to revision. The majority (74%) of
      patients expected their revision to last longer than their primary arthroplasty
      regardless of revision diagnosis or how long the primary procedure lasted before
      revision. The surgeons' failure assessments agreed with the patients' failure
      assessments only 34% of the time. Although the majority of patients (69%) were
      satisfied with the results of the revision procedure, most did not agree with
      their surgeon as to why the original arthroplasty failed, and most had
      unrealistic expectations regarding revision longevity. LEVEL OF EVIDENCE: Level
      II, prognostic study. See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 18062049
TI  - Morbidity of sequential bilateral revision TKA performed under a single
      anesthetic.
AB  - There are little data reporting perioperative morbidity and postoperative
      complications of bilateral sequential revision total knee arthroplasties (TKAs)
      performed in one anesthetic setting. We retrospectively reviewed 49 patients
      undergoing 51 complete (tibial and femoral components) bilateral revision TKAs
      under a single anesthetic between 1999 and 2006. The average age was 65 years;
      the minimum followup was 1 month (average, 12 months; range, 1-38 months).
      Comorbidities included cardiovascular (n = 32), pulmonary (n = 13), endocrine (n
      = 22), gastrointestinal (n = 30), and neurologic (n = 18). Average surgical time
      was 64 minutes per limb. Six patients received no stems, six received two stems,
      two patients received three stems, and 37 received four stems. We encountered no
      intraoperative complications and no patients with postoperative cardiovascular
      compromise, stroke, or death. Postoperative complications included confusion in
      three patients, one pulmonary embolism treated successfully with extended
      anticoagulation, one patient with posterior compartment syndrome treated with
      fasciotomy, and one with bilateral stiffness who underwent manipulation under
      anesthesia at 3 months. In our patients the perioperative medical risks of
      bilateral TKA performed under a single anesthetic were low, even with the use of
      stemmed components. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 18062050
TI  - A comparison of acetate and digital templating for total knee arthroplasty.
AB  - Accurate preoperative templating can facilitate precise, efficient, and
      reproducible total knee arthroplasty. We determined whether acetate templating
      accurately predicted knee implants used and compared the accuracy of digital
      templating. Preoperative planning was performed on 50 consecutive preoperative
      radiographs during 2005. After digital images were obtained, appropriately
      magnified analog films were printed. Four arthroplasty surgeons and one resident
      performed acetate templating and one arthroplasty surgeon trained in the
      technique performed digital templating. Acetate and digital templating accurately
      predicted the size of the implanted component to within one size, 91% versus 93%,
      respectively. The digital technique was more accurate than acetate for tibial
      component size. Acetate and digital templating did not differ in predicting
      femoral component size. Our data suggest digital templating is at least as
      accurate as traditional acetate templating for predicting knee implant sizing.
      LEVEL OF EVIDENCE: Level II, diagnostic study. See the Guidelines for Authors for
      a complete description of levels of evidence.

PMID- 18062051
TI  - A validation study of the New Zealand score for hip and knee surgery.
AB  - In the absence of consensus over criteria for performing total knee arthroplasty,
      the variability of symptom burden, and limited resources, some ways to prioritize
      whether and when to treat would be useful. In the UK, some payers use the New
      Zealand score to determine access to an orthopaedic surgeon despite limited
      validation. We tested convergent validity of this score and ascertained its
      ability to discriminate between groups of patients with high or low disease
      burden as determined by a validated disease-specific measure. The sample included
      patients being considered for total knee arthroplasty at one hospital. Convergent
      validity was tested against the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC). The ability of the New Zealand score to
      discriminate between high and low disease burdens was tested by plotting a
      receiver operating characteristic curve. Correlations between the New Zealand
      score and WOMAC pain and function were moderate (0.5 and 0.54, respectively). The
      area under the receiver operating characteristic curve was 0.77, suggesting the
      New Zealand score was able to discriminate. This study supports the validity of
      the New Zealand score. However, additional multisite and extended evaluations are
      needed before we would recommend widespread implementation. LEVEL OF EVIDENCE:
      Level I, economic and decision analyses. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 18062052
TI  - Clinical validation of model-based RSA for a total knee prosthesis.
AB  - Roentgen stereophotogrammetric analysis generally is accepted as the most
      accurate method to measure prosthesis migration. A disadvantage of the method is
      it requires markers in the bone and the prosthesis. Model-based roentgen
      stereophotogrammetric analysis circumvents the need for markers on prostheses by
      fitting virtual projections of a three-dimensional surface model of a prosthesis
      to its actual projections in the roentgen image. We confirmed a model-based
      roentgen stereophotogrammetric analysis for a tibial component. Using implants
      with attached markers, we compared model-based roentgen stereophotogrammetric
      analysis with marker-based roentgen stereophotogrammetric analysis. In addition,
      we assessed precision of the model-based roentgen stereophotogrammetric analysis
      with a phantom experiment. The precisions for translations of marker-based and
      model-based roentgen stereophotogrammetric analysis were 0.06 and 0.11 mm,
      respectively, and for rotations, the precisions were 0.20 degree and 0.23 degree,
      respectively. The precisions of model-based roentgen stereophotogrammetric
      analysis calculated from the phantom data were 0.08 mm for translations and 0.13
      degree for rotations. Although model-based roentgen stereophotogrammetric
      analysis is less precise than marker-based roentgen stereophotogrammetric
      analysis, its precision is still acceptable for most clinical applications,
      especially where marker-based roentgen stereophotogrammetric analysis has
      practical limitations. LEVEL OF EVIDENCE: Level II, prognostic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 18062053
TI  - Response to a geezer's lament.

PMID- 18062054
TI  - Burnout among Dutch medical residents.
AB  - We examined levels of burnout and relationships between burnout, gender, age,
      years in training, and medical specialty in 158 medical residents working at the
      University Medical Center Groningen, the Netherlands. Thirteen percent of the
      residents met the criteria for burnout, with the highest percentage of burnout
      cases among medical residents in Psychiatry. Significantly more male residents
      than female residents suffered from severe burnout. Medical residents reported
      significantly lower mean scores on personal accomplishment than medical
      specialists and other health care workers; they also reported lower mean scores
      on emotional exhaustion than medical specialists. Male residents had
      significantly higher depersonalization scores than female residents. Positive
      significant relationships were found between personal accomplishment and age and
      years in training. Obstetrics & Gynecology residents reported significantly more
      personal accomplishment than residents in Psychiatry, Internal Medicine,
      Pediatrics, and Anesthesiology. Residents in Psychiatry had significantly lower
      scores on personal accomplishment than residents in Internal Medicine. Our
      findings show that burnout is present in a small but significant number of
      medical residents.

PMID- 18062055
TI  - Psychometric properties of the Chinese version of Copenhagen burnout inventory
      among employees in two companies in Taiwan.
AB  - This study examined the psychometric properties of two selected scales--'personal
      burnout' and 'work-related burnout'--from the Chinese version of the Copenhagen
      Burnout Inventory (C-CBI) in 384 employees from two companies in Taiwan. A self
      administered questionnaire was used that included the two C-CBI scales, the
      scales of mental health, vitality and general health from the Short Form 36 (SF
      36), perceived level of job stress, job satisfaction, working hours, as well as
      measures for psychological job demands, job control, work-related social support,
      and over-commitment to work. Both the C-CBI personal burnout scale and work
      related burnout scale had high internal consistency and were correlated well with
      other health, job characteristics, and perception of work measures;furthermore,
      exploratory factor analysis extracted two empirical factors. However, the two C
      CBI scales were highly correlated in the present population and appeared to
      measure overlapping concepts. Some comments and suggestions were raised for
      further improvement.

PMID- 18062058
TI  - The role of partner relationships in the young person's adherence to the diabetes
      self-care regime.
AB  - BACKGROUND: This study investigated the role of partner relationships in the
      young person's experience of diabetes. It was predicted that those people
      reporting a better quality relationship would report greater social support and
      better diabetes management. METHOD: Fifty young adults with diabetes and their
      spouse/partner completed web-based questionnaires. RESULTS: A better quality
      relationship did not correlate with high reported levels of social support or
      with better diabetes management. Path analysis demonstrated, however, that for
      males with diabetes high reported quality of relationship predicted better
      diabetes management. CONCLUSIONS: Relationship quality does not generally predict
      better diabetes management; however, there may be a unique feature to good
      relationships that support men's diabetes self-care.

PMID- 18062057
TI  - Psychosocial predictors of medication adherence among persons living with HIV.
AB  - BACKGROUND: Since the introduction of highly active antiretroviral therapy
      (HAART), many have learned to live with HIV as a chronic illness. Adherence to
      medical regimens is extremely important for HIV patients. PURPOSE: To examine the
      extent to which medication adherence among HIV patients is related to social and
      psychological variables. METHOD: Data were gathered among 127 HIV patients (aged
      from 18-65 years) recruited at their quarterly consultation at Metz Hospital
      (France). Subjects completed a self-report adherence to medication scale, the
      Illness Perception Questionnaire (IPQ), the Beliefs about Medicine Questionnaire
      (BMQ), a French Value System Scale, a treatment satisfaction scale, and
      sociodemographic measures. RESULTS: Analyses revealed significant associations
      between adherence and patients' beliefs about treatment, satisfaction with
      treatment, confidence in the physician, some values ("other people," "god and
      children"), and duration of treatment and illness. CONCLUSION: The data suggest
      that patients' beliefs about treatment are formed to a certain degree in the
      patients' relationship with the physician. Furthermore, adherence seems to be
      related to personal values.

PMID- 18062056
TI  - Silent myocardial ischemia and cardiovascular responses to anger provocation in
      older adults.
AB  - To determine if older, asymptomatic individuals with no prior history of coronary
      heart disease with exercise-induced silent myocardial ischemia (SI) during graded
      exercise treadmill testing exhibit exaggerated cardiovascular reactivity to anger
      provocation, we compared 42 SI participants and 95 controls. Systolic blood
      pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) changes from
      baseline to three tasks--anger recall, speech role-play, and mental arithmetic
      with harassment--were assessed. Compared to controls, SI displayed greater HR
      responses for the speech role-play task only. The SI group was significantly
      older, had higher levels of fasting glucose and triglycerides, and had lower HDL
      cholesterol. In multiple regression analyses, after controlling for these
      differences, SI was significantly associated with greater HR responses to the
      speech role-play. In sum, the SI group significantly exaggerated HR responses to
      the speech role-play task, whereas SBP and DBP reactivity were comparable between
      groups. This suggests minimally enhanced cardiovascular reactivity among older SI
      patients that may nonetheless increase risk for cardiac events.

PMID- 18062059
TI  - Cognitive behavioral stress management intervention improves quality of life in
      Spanish monolingual hispanic men treated for localized prostate cancer: results
      of a randomized controlled trial.
AB  - BACKGROUND: The efficacy of a group-based psychosocial intervention with ethnic
      minority health populations may depend on consideration for cultural factors that
      can interact with group processes. PURPOSE: The current study explored the
      efficacy of a 10-week group-based cognitive-behavioral stress management (CBSM)
      intervention that was linguistically and culturally adapted for use with Hispanic
      monolingual men recently treated for localized prostate carcinoma (PC). METHODS:
      71 Hispanic mono-lingual Spanish speakers were randomly assigned to a 10-week
      CBSM intervention or a half-day stress management seminar (control condition).
      Hierarchical regression was used to predict post-intervention QoL. RESULTS: After
      controlling for relevant covariates, assignment to the CBSM condition
      significantly predicted greater physical well-being, emotional well-being, sexual
      functioning, and total well-being after the 10-week intervention period.
      CONCLUSIONS: Results suggest that participation in a culturally and
      linguistically adapted CBSM group intervention improved QoL in Hispanic
      monolingual men treated for localized PC.

PMID- 18062060
TI  - Subjective health and illness, coping and life satisfaction in an 80-year-old
      Swedish population-implications for mortality.
AB  - BACKGROUND: Multimorbidity and illness will become more common due to increased
      life expectancy. PURPOSE: This study describes various combinations of diseases
      and symptoms and explores implications for mortality in a sample of 80-year-olds
      followed up to 95 years of age. Furthermore, reported subjective health, coping,
      and life satisfaction is explored. METHOD: 212 persons, born in 1908, were
      classified into four groups based on their number of diseases and reported
      symptoms according to a health examination at the age of 80. These groups were
      compared regarding standardized measurements of subjective health, depression,
      coping, life satisfaction, and mortality. RESULTS: The mortality risks, the
      hazard ratios, were of the same magnitude, 1.8-2.2, whether the persons
      experienced several symptoms, had several diseases, or a combination of several
      symptoms and several diseases when compared to the healthy group of respondents.
      CONCLUSION: The experience of subjective signs of illness carries the same
      mortality risks as diseases.

PMID- 18062061
TI  - Inequalities in smoking: influence of social chain of risks from adolescence to
      young adulthood: a prospective population-based cohort study.
AB  - BACKGROUND: The pathway between socioeconomic disadvantages and smoking is a
      process that requires an understanding of life-course influence. PURPOSE: This
      study investigated pathways of social risks at different life stages that are
      linked to adolescent smoking and maintenance of smoking through to young
      adulthood. METHOD: A cohort consisting of all pupils (n = 1083) from one Swedish
      city were followed from age 16 to age 30 (1981-1995), with a 96.4% response rate.
      RESULT: Odds ratios of being a smoker at age 30 among low educated were 2.54 for
      men and 2.53 for women. Using structural equation model analysis for men and
      women, a strong chain of risks was found from age 16 linking to smoking at age
      30: adolescents with adverse socioeconomic status (SES) were more likely from a
      divorced family. Being from a divorced family and having poor contact with their
      parents influenced their smoking directly and through peers. Adolescents with
      adverse SES were also likely to be unpopular in school, which affected their
      smoking behavior directly and through peers. These socially disadvantaged
      participants, who were smokers at age 16, continued smoking until age 30 years.
      The risk pathways were similar for both men and women. CONCLUSIONS: Adult smoking
      reflects the cumulative influence of multiple socioeconomic and psychosocial
      chains of risks experienced during upbringing. The programs that are addressed to
      reduce smoking among socially disadvantaged adolescents would have an impact in
      reducing smoking inequalities in adults.

PMID- 18062062
TI  - The epidemiology of viral meningitis hospitalization in childhood.
AB  - BACKGROUND: There have been few long-term population-based studies of viral
      meningitis, and only a limited number of potential risk factors have been
      evaluated. METHODS: We estimated the incidence of viral meningitis
      hospitalization in childhood, and assessed risk factors for this disease through
      a population-based cohort study comprising all children born in Denmark from 1977
      through 2001 (n = 1.5 million). Information on sex, number of children and adults
      in the household, age of parents at child's birth, degree of urbanization, birth
      weight, gestational age, and possible complications at birth were linked to the
      children in the cohort, together with information on hospitalization with viral
      meningitis. We calculated incidence rates of viral meningitis and estimated rate
      ratios according to the various risk factors using Poisson regression. RESULTS:
      The incidence rate was highest in the first 6 months of life (38.7 per 100,000
      person-years), with a peak right after birth (58.7 per 100,000 person-years). A
      secondary peak was seen among 5-year-old children (15.6 per 100,000 person
      years). Overall incidence rates decreased throughout the study period, with
      outbreaks occurring every 3 to 5 years [decrease in rate ratio per calendar year
      = 0.95; 95% confidence interval (CI) = 0.94-0.96]. Summer and early fall peaks
      were present. We observed independent effects of sex (girls vs. boys: rate ratio
      = 0.47 [95% CI = 0.43-0.53]), children in the household (eg, living with 3+
      younger children vs. living with none: 1.94 [1.22-3.07]), single parenthood
      (living with 1 parent vs. living with 2 parents: 1.30 [1.12-1.39]), degree of
      urbanization (children living in the capital vs. children living in small town
      and rural areas: 1.54 [1.31-1.80]), low birth weight (increase in RR per 500 g
      reduction in birth weight = 1.05 [1.00-1.09]), prematurity (increase in RR per 1
      week reduction in gestational age = 1.03 [1.01-1.04]), and cesarean section
      (cesarean section vs. vaginal birth: 1.29 [1.12-1.49]). CONCLUSIONS: Incidence of
      viral meningitis hospitalization is highest immediately after birth with a
      secondary peak at age 5. Lack of passive maternally acquired antibodies and
      preferential hospitalization are the likely causes for the peak in infancy.
      Increased transmission in kindergarten, preschool, and day care could explain the
      secondary peak. The incidence decreased throughout the 25-year study period
      perhaps due to improved public hygiene. Among the assessed risk factors, we found
      the strongest to be male sex, a high number of children in the household, and
      degree of urbanization.

PMID- 18062063
TI  - Adipokines in human milk and risk of overweight in early childhood: a prospective
      cohort study.
AB  - BACKGROUND: Multiple studies have suggested that breast-feeding can prevent
      obesity, but the evidence remains inconclusive. The concentrations of specific
      constituents of human milk, such as adipokines, may play a role in this
      relationship, and these have rarely been considered. We assessed the role of
      adiponectin and leptin in human milk in childhood overweight. METHODS: Between
      November 2000 and November 2001 all women delivering at the Department of
      Gynecology and Obstetrics at the University of Ulm, Germany were invited to
      participate in the study together with their healthy newborns. Milk samples were
      collected 6 weeks postpartum. Adiponectin and leptin levels were determined by
      commercially available ELISA. Active follow-up was performed at age 12 and 24
      months. RESULTS: Of the 674 breast-fed children, 56 (8%) were overweight at the
      age of 2 years. Median adiponectin and leptin levels in milk were 10.9 ng/mL and
      174.5 pg/mL, respectively. Adjusted odds ratio for overweight at the age of 2 was
      1.6 (95% confidence interval = 1.0-2.6) per unit increase of log adiponectin and
      1.1 (0.8-1.5) per unit increase of log leptin. Among children who were breast-fed
      for at least 6 months, adjusted odds ratios were 2.1 (1.1-4.2) per unit increase
      of log adiponectin, and 1.1 (0.7-1.6) per unit increase of log leptin.
      CONCLUSION: High levels of adiponectin in maternal milk may be a risk factor for
      childhood overweight.

PMID- 18062064
TI  - Occupational exposures, environmental tobacco smoke, and lung cancer.
AB  - BACKGROUND: There is uncertainty regarding the association of occupational
      exposures with lung cancer. We have studied the association between 52 high-risk
      job titles and lung cancer incidence in a large prospective study, with more than
      200,000 participants followed for more than 6 years and 809 incident cases of
      lung cancer. METHODS: Hazard ratios and 95% confidence intervals were computed by
      the Cox proportional-hazard regression model, adjusting for country, age, sex,
      social class, diet, physical activity, and smoking habits. We used a CAREX-based
      job-exposure matrix to infer exposure to lung carcinogens. False-positive report
      probability was calculated as a measure of potentially false-positive results.
      RESULTS: Eighteen occupations, mainly related with agriculture, constructions,
      and metal processing, were associated with increased risk. In addition, incidence
      tended to increase with the number of hazardous jobs reported. When the
      occupations were classified according to the presumed exposure to specific
      carcinogenic agents, the hazard ratios were 1.5 (95% confidence interval = 1.2
      1.9) for asbestos, 1.4 (1.1-1.8) for heavy metals, 1.4 (1.1-1.8) for polycyclic
      aromatic hydrocarbons, and 1.6 (1.2-2.1) for work-related environmental tobacco
      smoke. The estimated population attributable risk for employment in at least 1 at
      risk job was 16% in men and 12% in women. CONCLUSIONS: This large prospective
      study suggests that exposure to occupational lung carcinogens is still a problem,
      with such exposures producing moderate to large increases in risk.

PMID- 18062065
TI  - Pressure grows against homeopathy in the UK.

PMID- 18062066
TI  - Bibliography. Current world literature. Androgens.

PMID- 18062067
TI  - SSAT patient care guidelines. Management of colonic polyps and adenomas.

PMID- 18062068
TI  - Proceedings of the 10th Annual Meeting of the Society of Biotherapeutic
      Approaches, December 2, 2006, Fukuoka, Japan.

PMID- 18062070
TI  - SSAT patient care guidelines. Surgical treatment of cancer of the colon or
      rectum.

PMID- 18062069
TI  - Inulin and oligofructose: proven health benefits and claims. Proceedings of the
      5th ORAFTI Research Conference, September 28-29, 2006, Boston, Massachusetts.

PMID- 18062071
TI  - SSAT patient care guidelines. Management of ulcerative colitis.

PMID- 18062072
TI  - SSAT patient care guidelines. Surgical treatment of reflux esophagitis.

PMID- 18062073
TI  - SSAT patient care guidelines. Esophageal achalasia.

PMID- 18062075
TI  - SSAT patient care guidelines. Surgical treatment of esophageal cancer.

PMID- 18062074
TI  - SSAT patient care guidelines. Management of Barrett's esophagus.

PMID- 18062076
TI  - SSAT patient care guidelines. Surgery for obesity.

PMID- 18062077
TI  - SSAT patient care guidelines. Treatment of gallstone and gallbladder disease.

PMID- 18062078
TI  - SSAT patient care guidelines. Cystic neoplasms of the pancreas.

PMID- 18062079
TI  - SSAT patient care guidelines. Surgical repair of groin hernias.

PMID- 18062080
TI  - SSAT patient care guidelines. Surgical repair of incisional hernias.

PMID- 18062081
TI  - Notice of duplicate publication.

PMID- 18062082
TI  - Retraction notice to "Biomarkers for oxidative stress status of DNA, lipids, and
      proteins in vitro and in vivo cancer research." [Toxicology 229 (2007) 1-10].

PMID- 18062083
TI  - Abstracts of the 56th Annual Meeting of the American Society of Tropical Medicine
      and Hygiene, November 4-8, 2007, Philadelphia, Pennsylvania, USA.

PMID- 18062084
TI  - Extubation after cardiothoracic surgery in neonates, children, and young adults:
      one year of institutional experience.
AB  - OBJECTIVE: Describe risk factors associated with successful and early extubation
      in the pediatric cardiac intensive care unit. DESIGN: Retrospective chart review.
      SETTING: University hospital, cardiac intensive care unit. MEASUREMENTS AND MAIN
      RESULTS: Review of 212 consecutive surgical admissions from January 2003 to
      January 2004, excluding deaths. Preoperative, intraoperative, and postoperative
      variables were studied. Successful extubation was defined as no reintubation at
      any time during the cardiac intensive care unit course and early extubation was
      defined as mechanical ventilation < or =24 hrs. Median subject age was 8 months
      (range, 1 day-25 yrs), with 57% <1 yr of age and 22% neonates. Fifty-eight (27%)
      were extubated in the operating room and 122 (58%) were extubated at <24 hrs
      (mean, 6.1 +/- 7.7 hrs). Only seven patients failed extubation: three in the
      operating room because of upper airway obstruction and four in the cardiac
      intensive care unit for acute respiratory failure associated with atelectasis (n
      = 2), ventricular dysfunction (n = 1), and arrhythmia (n = 1). There were no
      extubation failures in patients extubated >24 hrs after surgery. A history of
      prematurity (odds ratio [OR], 5.84, 2.29-14.9; p < .001), base excess (OR, 1.47,
      1.27-1.70; p < .001), cardiopulmonary bypass time (OR, 1.01, 1.01 to -1.2; p <
      .05), and the need for surgical reintervention (OR, 18.29, 2.78 to -120.07; p <
      .05) were associated with intubation for >24 hrs. CONCLUSION: Extubation without
      the need for reintubation can be achieved in nearly all children following
      cardiothoracic surgery. The majority of successful extubations can be achieved
      within 24 hrs of surgery

PMID- 18062085
TI  - Use of recombinant activated factor VII in intractable bleeding during pediatric
      neurosurgical procedures.
AB  - OBJECTIVE: To report the use of recombinant activated factor VII (NovoSeven; Novo
      Nordisk A/S, Bagsvaerd, Denmark) in children undergoing major neurosurgical
      procedures and experiencing massive uncontrolled hemorrhagic shock. DESIGN:
      Retrospective review of patients and analysis of clinical and biological effects
      of an intravenous administration of recombinant activated factor VII. SETTING:
      Neurosurgical anesthesia and critical care unit of a pediatric university
      hospital. PATIENTS/SUBJECTS: Four children, <12-kg body weight, experiencing life
      threatening perioperative hemorrhage required conventional treatment (massive red
      blood cells, fresh frozen plasma, platelet transfusion, and surgical hemostatic
      maneuvers) that failed to obtain definite hemostasis. INTERVENTIONS: Intravenous
      administration of recombinant activated factor VII (100 microg/kg). RESULTS:
      Intravenous administration resulted in a significant decrease in blood loss
      within minutes (preventing further need of transfusion), normalization of
      biological hemostasis markers, and improved surgical hemostasis. No side effects
      of recombinant activated factor VII were noted, and all patients, except one, had
      a good recovery. CONCLUSIONS: These four patients support the use of recombinant
      activated factor VII as a useful adjunct to control massive life-threatening
      bleeding during pediatric neurosurgical procedures when other means failed.
      However, the data are still limited in children, and more extensive research is
      needed to define the indications of recombinant activated factor VII in massive
      surgical hemorrhage in low-weight children.

PMID- 18062086
TI  - Correction. Comparison of access-related bleeding complications in women versus
      men undergoing percutaneous coronary catheterization.

PMID- 18062087
TI  - [Importance of pain science in the making of a physician. A missing link in
      Russian medical education].

PMID- 18062088
TI  - [Sevoflurane anesthesia during reconstructive operations on the carotid
      arteries].

PMID- 18062089
TI  - [Correction of hemodynamic changes during aortofemoral bifurcation bypass surgery
      under combined epidural anesthesia].
AB  - Assessment of hemodynamic parameters in 50 patients before aortofemoral
      bifurcation bypass surgery could identify 3 types of baseline central
      hemodynamics and differentiate methods for correcting its disorders. It was
      ascertained that the development of the intraoperative reperfusion phenomenon
      during epidural block might predispose to the low cardiac output syndrome for
      which correction ganglionic blockers are effective at the stage of aortic
      ligation and a combination of inotropic agents and venous vasodilators is
      beneficial at the stage of reperfusion.

PMID- 18062090
TI  - [Intensive care and anesthetic maintenance in intra-abdominal hypertension].
AB  - The purpose of this review to show recent advances in the treatment of
      intraabdominal hypertension and abdominal compartment syndrome and to evaluate
      their clinical implication. To identify relevant publications, the authors have
      looked through the MEDLINE, EMBASE, and Cochrane Library for the original papers
      published since 1980. As search terms, they used "intraabdominal pressure",
      "intraabdominal hypertension", "abdominal compartment syndrome combined with
      treatment". The cumulative analysis of recent data indicates that early treatment
      of intraabdominal hypertension can prevent the development of abdominal
      compartment syndrome and a need for emergency laparotomy. However, laparotomy and
      various laparostomic techniques remain the only effective methods in treating
      intraabdominal hypertension in the presence of the abdominal compartment
      syndrome. The staf of surgical and general intensive care units should be aware
      of the prevention and treatment of intraabdominal hypertension and abdominal
      compartment syndrome.

PMID- 18062091
TI  - [Ultrasound transcranial monitoring during aortocoronary bypass surgery under
      extracorporeal circulation].
AB  - The paper deals with the assessment of hemodynamic parameters in the region of
      the circle of Willis, by using various exercise tests and transcranial Doppler
      study during cardiac operations under extracorporeal circulation. Some points of
      the timely diagnosis of air and material microembolisms are specified. There is
      evidence that the application of these procedures is substantiated and they may
      be employed in clinical practice to undertake earlier preventive measures against
      cervical circulatory disorders.

PMID- 18062092
TI  - [Sepsis and multiple organ dysfunctions--pathophysiology and the topical concepts
      of treatment].
AB  - Severe sepsis with multiple organ dysfunctions is still the leading cause of
      death in non-cardiac intensive care units (ICU). The incidence is expected to
      rise in the future due to the growing number of older and immunocompromized
      patients, the use of invasive procedures, and an increase in the percentage of
      aggressive or resistant microorganisms. Despite the enormous investment in
      critical care resources, severe sepsis mortality remains to be high and ranges
      from 28 to 50%. Based on the disappointing experiences with anti-inflammatory
      strategies, the authors now realize that sepsis is more than just an
      inflammation. By taking into account pathophysiological changes, the new
      therapeutic concepts combine successful modulation with an improvement of the ICU
      management of multiple organ dysfunctions. This review discusses the actual
      sepsis intensive care concepts that may be useful in reducing unacceptable high
      mortality rates in patients with severe sepsis.

PMID- 18062093
TI  - Myelodysplastic syndrome associated with isolated del (5q) chromosome abnormality
      ("5q- syndrome").

PMID- 18062094
TI  - Biotronik Brazil - completing 25 years of success.

PMID- 18062095
TI  - [On the anniversary of the Moscow City Research-and-Practical Center for
      Tuberculosis Control, Department of Health Care of the city of Moscow].

PMID- 18062096
TI  - [Mycobacterium non-tuberculosis: classification, epidemiology, pathology in man
      and animals, laboratory diagnosis].

PMID- 18062097
TI  - [Basic principles, objectives, and legislative base of clinical studies in
      phthisiology].

PMID- 18062098
TI  - [Tuberculosis and HIV infection: detection, follow-up, treatment: Moscow data].
AB  - The paper describes the follow-up and treatment of patients with tuberculosis
      concurrent with HIV infection in Moscow in 2004-2005. Major epidemiological
      parameters, such as morbidity, mortality, and prevalence of this comorbidity, are
      given. Analysis of these indices suggests that the epidemic situation associated
      with tuberculosis concurrent with HIV infection became worse in the past 2 years.
      As compared with 2004, in 2005 the number of such patients increased from 294 to
      445, including that of first detected patients rose from 123 to 174. In this
      group of patients, there was a preponderance of young males aged 29 to 39 years.
      Most patients with this pathology suffered from drug addiction and alcoholism and
      other concomitant diseases. The bulk of them were unemployed and disabled. In the
      HIV-infected, the clinical forms of tuberculosis were severe with a predominance
      of acute and disseminated processes; the rate of drug resistance, including
      multidrug resistance, was high, which made treatment difficult and resulted in
      high mortality.

PMID- 18062099
TI  - [Organization of emergency health care to patients with tuberculosis].
AB  - Tuberculosis hospital No. 7 is an emergency general tuberculosis institution. In
      2005, a total of 3847 patients were sent to the reception room; out of them 2045
      were delivered by ambulances. That year, there were 568 emergency surgical
      interventions for comorbidity (n=343) and tuberculosis and its complications
      (n=225). The high availability of current diagnostic procedures and the presence
      of different skilled medical specialists enable one to promptly establish the
      diagnosis, which improves prognosis and reduces the length of hospital stay and
      the number of admission to tuberculosis and general hospitals. Tuberculosis
      hospital No. 7 provides diagnostic and therapeutic (primary) aids to patients who
      need no hospital care, which reduces the potential time of disability. The
      activity of tuberculosis hospital No. 7 is aimed at upgrading the quality of
      medical aid, reducing the number of wrongful admissions and the length of
      hospital stay, improving the occupational and social prognosis in patients with
      tuberculosis, and considerably saving the budgetary funds of the Moscow
      Department of Health Care.

PMID- 18062100
TI  - [Criteria for clinical recovery and the evaluation of the efficiency of treatment
      in patients with respiratory tuberculosis in Moscow].
AB  - Criteria for clinical cure have been analyzed and the efficiency of treatment
      evaluated in patients with respiratory tuberculosis in Moscow. If today's
      official criteria for the efficiency of treatment have been ascertained to
      preserve in treating the first detected patients, a phthisiological service will
      completely lose an objective control of this section of work in several years.
      The only criterion that gives some idea of the results of treatment in first
      detected patients is currently to transfer them to dispensary register group III.
      However, when the results of interim treatment stages are unknown, conditions are
      created for utter arbitrariness in the time of the transfer (this happens at
      present). It is necessary to hold today's existing major criteria (cessation of
      bacterial isolation and closure of decay cavities) for evaluating the efficiency
      of treatment in first detected patients (who are largely inpatients) and to add
      one more criterion (disappearance of Xray signs of active tuberculosis
      manifestations); moreover, the magnitude of major or minor residual tuberculous
      changes should be, of course, taken into account after a basic course of
      chemotherapy.

PMID- 18062101
TI  - [Psychosomatic characteristics of patients with pulmonary tuberculosis].
AB  - Medical and psychological studies have established that the personality of a
      psychosomatic patient has characteristic specific features that determine his
      emotional reactions and lead to psychological and physiological destructions.
      Searching for the specificity of psychogenesis of pulmonary tuberculosis may be
      guided by the V. N. Myasishchev provisions of psychology of relations and should
      be aimed at analyzing the patients' significant experiences that cause their
      prolonged affective tension. This paper defines the tasks of studying the
      psychological and neuropsychological features of patients with pulmonary
      tuberculosis and specifies an adequate set of psychodiagnostic procedures to
      solve the put problems. The findings may provide insight into the specific
      character of psychogenesis of pulmonary tuberculosis and into a relationship of
      the psychological traits of patients with this nosological entity to the
      physiological processes at the somatic and cerebral level.

PMID- 18062102
TI  - [A difficult case of diagnosis of exudative pericarditis of mixed etiology].

PMID- 18062103
TI  - [Occupationally related morbidity and its evidence].
AB  - The article deals with problem of occupationally related diseases, examples and
      evidence. The authors analyzed role of periodic medical examinations in diagnosis
      of occupationally related diseases, considered a triad for their diagnosis: flow
      chart, algorithm table and numerical scale. Suggestions on improving periodic
      medical examinations for diagnosing occupationally related diseases are
      presented.

PMID- 18062104
TI  - [Roentgenometry in complex diagnosis of fluor osteopathy caused by occupational
      factors].
AB  - The author demonstrated that roentgenometric methods enabled objectivation of
      bone transformation intensity in osteosclerosis and osteoporosis, specification
      of objective criteria for bone fluorosis.

PMID- 18062105
TI  - [Morbidity and reproductivity parameters in male metallurgists].
AB  - The authors present results of comparative studies concerning general morbidity
      and reproductivity among workers of 'Krasny Oktyabr" metallurgic enterprise. Male
      metallurgists demonstrated significantly higher general morbidity. Sperm count
      and hormonal levels of those male metallurgists could signify reliably decreased
      reproductive health.

PMID- 18062106
TI  - [All-Russian scientific and practical conference "Oil and health" dedicated to
      75th anniversary of Bashkir oil].

PMID- 18062107
TI  - Clinical evaluation of the combination of anorganic bovine-derived hydroxyapatite
      matrix/cell-binding peptide (P-15) in particulate and hydrogel form as a bone
      replacement graft material in human periodontal osseous defects: 6-month reentry
      controlled clinical study.
AB  - BACKGROUND: This prospective, randomized, controlled clinical trial study
      compared the clinical outcomes of the biomaterial anorganic bovine-derived
      hydroxyapatite matrix/cell-binding peptide (ABM/P-15) as a biocompatible hydrogel
      carrier consisting of carboxymethylcellulose and glycerol or in particulate form
      when used as a bone replacement graft in the treatment of human periodontal
      infrabony defects. METHODS: Nineteen patients with advanced chronic periodontitis
      were recruited. All patients had at least two non-adjacent intrabony osseous
      defects > or = 3 mm after completion of cause-related periodontal therapy. The
      surgical procedures included access flaps for root instrumentation and filling
      the defect with ABM/P-15 in hydrogel or particulate form. Reentry access flap
      surgery was performed at 6 months. Changes in soft and hard tissue outcome
      measurements between baseline and 6 months were evaluated in all defects.
      RESULTS: At 6 months, no significant differences between ABM/P-15 hydrogel and
      ABM/P-15 particulate were demonstrated for the amount of defect fill (3.10 +/-
      0.85 mm [75.0%] versus 3.09 +/- 1.11 mm [73.7%], respectively) or defect
      resolution (85.8% versus 81.9%). Changes in soft tissue clinical outcomes did not
      show significant differences between the treatments. CONCLUSION: This trial
      failed to demonstrate superiority of the novel ABM/P-15 hydrogel therapeutic
      modality over the standard ABM/ P-15 particulate graft in the treatment of
      intrabony periodontal defects.

PMID- 18062108
TI  - Clinical evaluation of periodontal surgical treatment with an Er:YAG laser: 5
      year results.
AB  - BACKGROUND: The aim of the present study was to evaluate and compare the long
      term clinical outcomes of erbium-doped:yttrium, aluminum, and garnet (Er:YAG)
      laser-assisted periodontal flap surgery versus conventional treatment with the
      modified Widman flap procedure. METHODS: A total of 146 single-rooted
      periodontally involved teeth from 25 patients were included in this study. In
      each patient, left or right maxillary single-rooted teeth were assigned randomly
      to one of two groups: group A (Er:YAG laser) and group B (modified Widman flap
      surgery). Er:YAG laser was used to debride the bone pockets, scale the root
      surface, and trim the periodontal flap. Recession, probing depth (PD), clinical
      attachment level (CAL), plaque index (PI), gingival index (GI), and bleeding on
      probing (BOP) scores were recorded at baseline and at 3, 6, 12, 24, 36, 48, and
      60 months. RESULTS: Both treatments resulted in decreases in PD, PI, GI, and BOP,
      increases in gingival recession, and gains in CAL. PD reduction in group A versus
      group B was statistically significant at 6, 12, 24, and 36 months (P < 0.05).
      Gains in CAL were significantly greater in group A versus group B at 6, 12, 24,
      and 36 months. BOP scores were significantly lower in group A versus group B at 3
      and 6 months (P < 0.05). All other differences between treatment groups were not
      statistically significant. CONCLUSIONS: Surgical treatment of single-rooted teeth
      with chronic periodontitis using the Er:YAG laser yields greater PD reduction and
      gains in CAL for up to 3 years compared to conventional Widman flap surgery. The
      short-term results obtained with both treatments can be maintained over 5 years.

PMID- 18062109
TI  - Sinus floor augmentation with simultaneous implant placement in the severely
      atrophic maxilla: technical problems and complications.
AB  - BACKGROUND: A one-stage surgical technique has been adopted that allows
      simultaneous implant placement in as little as 1 to 2 mm of residual bone. The
      aim of this retrospective study was to describe results and complications in
      sinus augmentation of severely atrophic edentulous maxillae in patients with 1 to
      3 mm residual bone height and compare them to a group of patients treated
      following the standard protocol with residual bone height > 4 mm. METHODS: The
      study consisted of a study group (N = 25) and a control group (N = 30). All
      patients were consecutive admissions treated for one-stage sinus augmentation by
      one surgeon during the years 2001 to 2005. Patients' medical files were reviewed
      mainly regarding operative technical problems and complications. RESULTS:
      Included in the study were 60 sinuses and 164 simultaneous implants placed in
      grafted maxillary sinuses. Eight implants failed, seven of which were in the
      study group; three were in heavy smokers with residual bone of 1 to 3 mm. The
      success rate was 92% for the study group and 98.7% for the control group. A
      borderline statistically significant difference was found in the success rates
      between the groups using the Fisher exact test (P = 0.069). CONCLUSION: Sinus
      augmentation with simultaneous implant placement can be used to treat the
      atrophic maxilla in patients with 1 to 3 mm of vertical residual bone height when
      careful case planning and surgical techniques are used.

PMID- 18062110
TI  - Early soft tissue healing around one-stage dental implants: clinical and
      microbiologic parameters.
AB  - BACKGROUND: Despite the potential significance of early soft tissue healing to
      long-term outcomes, this aspect of one-stage dental implants has not been
      investigated. The purpose of this prospective study was to characterize clinical
      and microbiologic parameters of early soft tissue healing around dental implants
      placed following a one-stage protocol. METHODS: Twenty-one patients (11 females
      and 10 males, aged 18 to 78 years; two smokers) needing a single implant were
      included. Clinical parameters included probing depth, buccal flap thickness,
      papilla height, and bleeding on probing. Subgingival plaque samples were obtained
      pre- and postoperatively and analyzed using molecular techniques. RESULTS: The
      newly formed peri-implant sulcus probing depth remained fairly stable from 4 to
      12 weeks (P > 0.05). There was no statistically significant association between
      flap thickness or papillary height and number of implant bleeding sites at 12
      weeks (P > 0.05). Detection of known periodontal pathogens was rare.
      Fusobacterium nucleatum was present in 17 patients prior to surgery, and 71% of
      them became carriers of this bacterium at the implant site by the second
      postoperative week. The number of F. nucleatum-positive subjects around the
      implant was significantly lower than the number of F. nucleatum-positive subjects
      around teeth (P < 0.05). CONCLUSIONS: Peri-implant soft tissue clinical maturity
      may be established as early as 4 weeks following implant placement by a one-stage
      surgical protocol; neither preexisting flap thickness nor papillary height seemed
      to influence newly forming peri-implant sulcus depth or bleeding on probing
      prevalence. For the most part, the newly created peri-implant crevices were
      colonized by specific bacteria within 2 weeks.

PMID- 18062111
TI  - Culture of human gingival fibroblasts on a biodegradable scaffold and evaluation
      of its effect on attached gingiva: a randomized, controlled pilot study.
AB  - BACKGROUND: An adequate width of attached gingiva is necessary to maintain
      healthy periodontium, especially in orthodontics or restorative treatments in
      periodontics. The purpose of this study was to evaluate the width of attached
      gingiva after clinical application of a cultured gingival graft compared to a
      periosteal fenestration technique. METHODS: This study was conducted on nine
      patients (18 sites) with insufficient attached gingiva adjacent to at least two
      teeth in contralateral quadrants of the same jaw. A small portion (approximately
      3 x 2 x 1 mm) of attached gingiva (epithelial + connective tissue) was removed
      with a surgical blade. After culture of gingival fibroblasts, 2 x 10(5) cells in
      250 microl nutritional medium were added to 250 microl collagen gel. One tooth in
      each patient was randomized to receive a periosteal fenestration technique for
      gingival augmentation (control) or a tissue-engineered mucosal graft (test).
      Clinical parameters measured at baseline and 3 months included width of
      keratinized tissue, probing depth, and width of attached gingiva. RESULTS: An
      increased amount of keratinized tissue was seen at all treated sites after 3
      months. The mean increased amount of attached gingiva was 2.8 mm at test sites
      and 2 mm at control sites; this difference was significant (P < 0.05).
      CONCLUSION: Based on the results of this investigation, the tissue-engineered
      mucosal graft is safe and capable of generating keratinized tissue.

PMID- 18062112
TI  - A determination of the range of oral conditions submitted for microscopic and
      direct immunofluorescence analysis.
AB  - BACKGROUND: Direct immunofluorescence (DIF) testing is a useful adjunct for the
      diagnosis of immune-mediated oral vesiculobullous diseases, helping to identify
      separate, histologically similar, but prognostically different, conditions. It is
      unknown how often biopsy of these lesions yields positive DIF results. METHODS: A
      total of 270 consecutive archival cases submitted to a reference laboratory in
      Buffalo, New York, over a 2-year span were examined. These specimens were
      submitted to establish or rule out a diagnosis of a DIF-positive oral
      vesiculobullous disease. Demographic, clinical, and diagnostic information, based
      on conventional microscopic and DIF analysis, was tabulated. To assess the
      contribution of DIF to successful diagnosis, three pathologists examined the
      hematoxylin and eosin-stained slides of the known DIF-positive specimens without
      knowledge of the DIF results. RESULTS: Approximately 48% of the specimens
      demonstrated positive DIF findings and consisted of pemphigus vulgaris, mucous
      membrane pemphigoid, lichen planus, linear immunoglobulin A disease, and chronic
      ulcerative stomatitis. The remaining specimens had negative DIF findings and
      consisted of numerous non-specific inflammatory conditions. Of particular
      interest were several cases of epithelial dysplasia and squamous cell carcinoma.
      Of the DIF-positive cases, only pemphigus vulgaris could be diagnosed reliably by
      conventional microscopy alone. CONCLUSIONS: Approximately half of biopsies of
      oral conditions that clinically resembled typically DIF-positive vesiculobullous
      diseases did not yield positive findings on DIF testing. Instead, a wide range of
      oral diseases can mimic these lesions clinically. With the exception of pemphigus
      vulgaris, DIF is essential for establishing a definitive diagnosis for known DIF
      positive diseases.

PMID- 18062113
TI  - Periodontal disease at the biofilm-gingival interface.
AB  - BACKGROUND: A molecular epidemiologic study provided the opportunity to
      characterize the biology of the biofilm-gingival interface (BGI) in 6,768
      community-dwelling subjects. METHODS: Disease classifications and multivariable
      models were developed using clinical, microbial, inflammatory, and host-response
      data. The purpose was to identify new clinical categories that represented
      distinct biologic phenotypes based upon DNA checkerboard analyses of eight plaque
      bacteria, serum immunoglobulin G (IgG) titers to 17 bacteria, and the gingival
      crevicular fluid (GCF) levels of 16 inflammatory mediators. Five BGI clinical
      conditions were defined using probing depths (PDs) and bleeding on probing (BOP)
      scores. Subjects with all PDs < or = 3 mm were grouped as BGI-healthy (14.3% of
      sample) or BGI-gingivitis (BGI-G, 15.1%). Subjects with one or more PDs > or = 4
      mm [deep lesion (DL)] were divided into low BOP (18.0%), moderate BOP (BGI-DL/MB,
      39.7%), and severe BOP (BGI-DL/SB, 12.9%). RESULTS: Subjects with BGI-G had
      increased levels of Campylobacter rectus-specific serum IgG levels (P = 0.01),
      and those with BGI-DL/SB had increased IgG levels to Porphyromonas gingivalis (P
      < 0.0003) and C. rectus (P < 0.01). BGI-DL/SB subjects had an excessive GCF
      interleukin (IL)-1beta and prostaglandin E2 response and an enhanced chronic
      inflammatory response with significant increases in GCF IL-6 and monocyte
      chemotactic peptide-1. Within BGI-DL/SB subjects, more severe pocketing and BOP
      were associated with higher levels of GCF IL-1beta, not higher microbial counts
      or plaque scores. CONCLUSIONS: New BGI classifications create categories with
      distinct biologic phenotypes. The increased titers of C. rectus IgG among 68.5%
      of the BGI-G subjects and elevated P. gingivalis titers among BGI-DL/MB and BGI
      DL/SB subjects (63.8% and 75.7%, respectively) are strongly supportive of the
      microbial specificity of pathogenesis for BGI categories.

PMID- 18062114
TI  - Does periodontal disease reflect atherosclerosis in continuous ambulatory
      peritoneal dialysis patients?
AB  - BACKGROUND: Chronic infection and inflammation, including periodontitis, are
      linked to an increased risk for atherosclerosis. To investigate the possible
      adverse effects of periodontitis in continuous ambulatory peritoneal dialysis
      (CAPD) patients, we compared periodontal severity with inflammation and
      malnutrition, which are associated with poor atherosclerotic outcome in CAPD
      patients. METHODS: A total of 110 CAPD patients were included in this study to
      evaluate their clinical periodontal status by using the plaque index, gingival
      index, and periodontal disease index. Values for nutritional and inflammatory
      markers and atherosclerotic risk factors were included for analysis with the
      periodontal index. Analysis of variance, post hoc Tukey's honestly significant
      difference, univariate and multivariate linear regression analysis, Pearson
      correlation analysis, and chi2 analysis were used in the evaluation of the data.
      RESULTS: Poor oral health status was exhibited by 85.5% of our CAPD patients with
      periodontal disease. We found that age and longer dialysis duration were
      associated with the severity of periodontitis. Parameters of malnutrition and
      inflammation and atherosclerotic risk factors also were associated with poor
      periodontal status. We carried out multiple regression analysis and found that
      age, albumin level, and duration of dialysis were associated independently with
      the severity of periodontitis in CAPD patients. A higher percentage of patients
      in the severe periodontitis group had malnutrition (chi2 = 59.4; P < 0.001),
      inflammation (chi2 = 60; P < 0.001), and atherosclerosis (chi2 = 65.6; P <
      0.001). CONCLUSIONS: Periodontal health is poor in CAPD patients and correlates
      with markers of malnutrition, inflammation, and atherosclerosis. The diagnosis
      and treatment of periodontal diseases require better awareness.

PMID- 18062115
TI  - Effect of rinsing with an essential oil-containing mouthrinse on subgingival
      periodontopathogens.
AB  - BACKGROUND: Studies have shown that the nature and amount of supragingival plaque
      can influence the composition of the contiguous subgingival flora. The purpose of
      this study was to investigate the effect of rinsing with an essential oil
      antimicrobial mouthrinse on levels of representative subgingival bacteria in
      subjects with mild to moderate periodontitis. METHODS: This controlled study used
      a randomized, double-masked, 2 x 2 crossover design. After baseline subgingival
      sampling, 37 qualifying subjects rinsed with the essential oil mouthrinse or a
      negative control twice daily for 14 days, with a post-treatment sample obtained
      on day 15. Following a washout period, the procedure was repeated with the
      alternative rinse. Target organisms enumerated were Porphyromonas gingivalis,
      Fusobacterium nucleatum, Veillonella sp., and total anaerobes. Intergroup
      comparisons of post-treatment log-transformed colony forming unit counts were
      made using analysis of covariance. RESULTS: After 14 days of twice-daily rinsing,
      the level of each of the target subgingival organisms was significantly lower in
      the essential oil group than in the control group (P < 0.001), with percent
      reductions ranging from 66.3% to 79.2%. CONCLUSIONS: Rinsing with the essential
      oil antiplaque/antigingivitis mouthrinse can have significant antimicrobial
      activity against subgingival periodontopathogens. Most likely, the antimicrobial
      effect was mediated primarily by disruption of the contiguous supragingival
      plaque by the mouthrinse. Because studies have shown that control of
      supragingival plaque can influence the onset and/or progression of periodontitis,
      additional studies on non-prescription antimicrobial oral care products may lead
      to new regimens for decreasing the burden of periodontal diseases in the
      population.

PMID- 18062116
TI  - Effect of two different bioabsorbable collagen membranes on guided bone
      regeneration: a comparative histomorphometric study in the dog mandible.
AB  - BACKGROUND: This study compared bone regeneration following guided bone
      regeneration with two bioabsorbable collagen membranes in saddle-type bone
      defects in dog mandibles. METHODS: Three standardized defects were created,
      filled with bone chips and deproteinized bovine bone mineral (DBBM), and covered
      by three different methods: control = no membrane; test 1 = collagen membrane;
      and test 2 = cross-linked collagen membrane (CCM). Each side of the mandible was
      allocated to one of two healing periods (8 or 16 weeks). The histomorphometric
      analysis assessed the percentage of bone, soft tissue, and DBBM in the
      regenerate; the absolute area in square millimeters of the bone regenerate; and
      the distance in millimeters from the bottom of the defect to the highest point of
      the regenerate. RESULTS: In the 8-week healing group, two dehiscences occurred
      with CCM. After 8 weeks, all treatment modalities showed no significant
      differences in the percentage of bone regenerate. After 16 weeks, the percentage
      of bone had increased for all treatment modalities without significant
      differences. For all groups, the defect fill height increased between weeks 8 and
      16. The CCM group showed a statistically significant (P = 0.0202) increase over
      time and the highest value of all treatment modalities after 16 weeks of healing,
      CONCLUSIONS: The CCM showed a limited beneficial effect on bone regeneration in
      membrane-protected defects in dog mandibles when healing was uneventful. The
      observed premature membrane exposures resulted in severely compromised amounts of
      bone regenerate. This increased complication rate with CCM requires a more
      detailed preclinical and clinical examination before any clinical recommendations
      can be made.

PMID- 18062117
TI  - GCF MMP-8 levels in smokers and non-smokers with chronic periodontitis following
      scaling and root planing accompanied by systemic use of flurbiprofen.
AB  - BACKGROUND: Cigarette smoking has been identified as an important risk factor for
      the initiation and progression of chronic periodontitis (CP). The aim of this
      study was to investigate the effects of phase I periodontal therapy and
      adjunctive flurbiprofen administration on matrix metalloproteinase (MMP)-8 levels
      in gingival crevicular fluid (GCF) samples from smoking and non-smoking patients
      with CP. METHODS: Twenty-nine non-smoking and 29 smoking patients with CP were
      divided into four groups according to periodontal treatment modalities. Group 1
      (non-smokers with CP) and group 3 (smokers with CP) patients received daily 100
      mg flurbiprofen tablets in a 2 x 1 regimen for 10 days together with scaling and
      root planing (SRP). Patients in group 2 (non-smokers with CP) and group 4
      (smokers with CP) received placebo tablets in a 2 x 1 regimen for 10 days
      together with SRP. Plaque index (PI), gingival index (GI), probing depth (PD),
      and clinical attachment level (CAL) measurements were recorded; GCF samples were
      collected from each sampling area at baseline and after the 10-day period of drug
      intake by a single examiner who was unaware of the treatment modality. Assays for
      GCF MMP-8 were carried out by an enzyme-linked immunosorbent assay. RESULTS: All
      groups showed statistically significant reductions in PI and GI scores following
      the phase I periodontal treatment (P < 0.05), but no statistical differences were
      observed in PD and CAL scores after therapy. In all groups, the reduction of GCF
      MMP-8 levels after therapy was statistically significant compared to baseline
      levels (P < 0.001). When groups 1 and 3 and 2 and 4 were compared according to
      GCF MMP-8 levels after the therapy, no statistically significant differences were
      observed (P = 0.117 and P = 0.485, respectively). CONCLUSION: Flurbiprofen
      administration had no additional inhibitory effect over SRP alone on GCF levels
      of MMP-8 in smokers compared to non-smokers with CP.

PMID- 18062118
TI  - Gingival crevicular fluid levels of neopterin in healthy subjects and in patients
      with different periodontal diseases.
AB  - BACKGROUND: Neopterin, a metabolite of guanosine, belongs to the class of
      chemical compounds known as pteridines and is an early and valuable marker of
      cellular immunity. Recently, it was shown to be associated with the initiation
      and progression of periodontal disease. The aim of the present study was to
      assess the relationship between clinical parameters and concentrations of
      neopterin within gingival crevicular fluid (GCF) from inflamed gingiva and
      periodontitis sites before and after the treatment of periodontitis. METHODS:
      Sixty age (35 to 65 years)- and gender-matched (30 males and 30 females) subjects
      were recruited and divided into the following four groups of 15 subjects each
      based on gingival index, Ramfjord periodontal disease index, clinical attachment
      loss (CAL), and radiographic parameters (bone loss): healthy (group 1),
      gingivitis (group 2), mild periodontitis (group 3), and moderate to severe
      periodontitis (group 4). A fifth group consisted of the 15 subjects from group 4,
      6 to 8 weeks after treatment (scaling and root planing). GCF was collected from
      each patient, and the neopterin levels were determined by enzyme immunoassay.
      Results were analyzed statistically. RESULTS: The mean concentration of neopterin
      in GCF was the highest in group 4 (51 nmol/l) and the lowest in group 1 (1.36
      nmol/l). The mean neopterin concentrations in group 2 (9.69 nmol/l) and group 3
      (16.58 nmol/l) fell between the highest and lowest values. This suggested a
      positive correlation between CAL and GCF neopterin concentrations. Neopterin
      levels in group 4 decreased to 1.77 nmol/l after treatment (group 5).
      CONCLUSIONS: Neopterin increased in parallel with the severity of inflammatory
      disease. Its levels in GCF may be potentially useful as an indicator of
      periodontal inflammation and the host response.

PMID- 18062119
TI  - Toll-like receptor 2 and 4 gene polymorphisms in generalized aggressive
      periodontitis.
AB  - BACKGROUND: Toll-like receptors (TLRs) recognize exogenous ligands such as
      lipopolysaccharide and bacterial lipoprotein during the immune responses to
      pathogens. The aim of the present study was to investigate whether TLR2 and TLR4
      gene polymorphisms are related to susceptibility to generalized aggressive
      periodontitis (GAgP). METHODS: A total of 245 subjects were included in the
      present study. Genomic DNA was obtained from the peripheral blood of 90 patients
      with GAgP and 155 periodontally healthy subjects. Probing depth, clinical
      attachment loss, plaque accumulation, and bleeding on probing were recorded. The
      TLR2 gene Arg753Gln and Arg677Trp polymorphisms and TLR4 gene Asp299Gly and
      Thr399Ile polymorphisms were genotyped by the polymerase chain reaction
      restriction fragment length polymorphism method. The data were analyzed by chi2
      and Mann-Whitney U tests and logistic regression analysis. RESULTS: There was no
      significant difference in the distribution of TLR2 and TLR4 genotypes and allele
      frequencies between GAgP patients and healthy subjects (P > 0.05). The TLR2
      753Gln allele was found in 3.9% of the GAgP patients compared to 6.1% in the
      healthy group. The GAgP patients and healthy subjects did not show homozygosity
      for the TLR2 mutant alleles. The TLR2 677Trp mutant allele was not found in any
      of the subjects; 2.2% of the GAgP patients and 2.9% of the periodontally healthy
      subjects were identified as having the TLR4 299Gly polymorphic allele. With
      regard to the TLR4 399Ile polymorphic allele, 1.1% of the GAgP patients and 2.3%
      of the periodontally healthy subjects had this allele. CONCLUSIONS: The present
      study failed to find any significant association between the TLR polymorphisms
      and GAgP, potentially because of the small sample size. To the best of our
      knowledge, this was the first study to examine the prevalence of these
      polymorphisms in a Turkish population with aggressive periodontitis.

PMID- 18062120
TI  - Dose-dependent effects of platelet gel releasate on activities of human
      osteoblasts.
AB  - BACKGROUND: Platelet-rich plasma is used in oral and maxillofacial surgery;
      however, its real efficacy is debated. Also, the in vitro effects on bone
      specific functions are contradictory. Understanding the mechanisms of action of
      platelet-derived factors could be the basis for their proper use in clinical
      applications. METHODS: The functional parameters of osteoblasts (proliferation,
      alkaline phosphatase, collagen synthesis, and calcium deposition) were analyzed
      in vitro for 14 days in the presence of different concentrations (100%, 33%, and
      11%) of platelet gel releasate (PGR). RESULTS: Concentrations of 100% PGR and 33%
      PGR stimulated cells to proliferate more than 10% fetal calf serum. The effect on
      cell proliferation was dose dependent, and the addition of dexamethasone (dex)
      and beta-glycerophosphate (beta-GP) reduced the proliferative effects. Alkaline
      phosphatase activity was stimulated by 33% PGR and 11% PGR after 7 days and was
      induced further by dex and beta-GP. Also, collagen synthesis, measured on day 11,
      was stimulated by 33% PGR and 11% PGR. Calcium deposition, evaluated after 7 and
      14 days, was greatest in cells treated with PGR supplemented with dex and GP. The
      mineralization process increased with time; on day 14, calcium aggregates were
      observed in all cultures treated with PGR (100%, 33%, and 11%). CONCLUSIONS: PGR
      stimulated osteoblast proliferation in a dose dependent manner and, when used at
      33% and 11%, induced maximum levels of alkaline phosphatase and collagen
      synthesis. Moreover, in the presence of dex and beta-GP, PGR stimulated the end
      maturative status of cells as expressed by the deposition of calcium nodules.

PMID- 18062121
TI  - A p38 mitogen-activated protein kinase inhibitor arrests active alveolar bone
      loss in a rat periodontitis model.
AB  - BACKGROUND: Gram-negative bacterial species, such as Actinobacillus
      actinomycetemcomitans, contain lipopolysaccharide (LPS) that initiates the innate
      immune system, resulting in inflammatory alveolar bone loss. LPS activates Toll
      like receptors on membrane surfaces, stimulating many intracellular signaling
      cascades, including the p38 mitogen-activated protein kinase (MAPK). Activation
      of p38 signaling mediates inflammatory cytokine expression, contributing toward
      osteoclastogenesis and bone loss. The aim of this study was to determine whether
      the novel, orally active p38 MAPK inhibitor SD282 could arrest progression of LPS
      induced alveolar bone destruction in rats. METHODS: Three groups of female
      Sprague-Dawley rats received LPS injections to the palatal molar gingiva three
      times per week for 4 weeks to establish periodontitis. From weeks 5 through 8,
      two groups received the drug SD282 (N = 14) or 1% polyethylene glycol drug
      vehicle (N = 14) via oral gavage in addition to LPS injections. The third group
      continued to receive only LPS injections (N = 8). Microcomputed tomography was
      used to measure volumetric alveolar bone loss, expressed as bone volume fraction
      (BVF). Expression of interleukin (IL)-1 and -6 and tumor necrosis factor-alpha
      (TNF-alpha) was assessed by immunohistochemistry, and osteoclasts were enumerated
      by tartrate-resistant acid phosphatase staining. RESULTS: By 4 weeks, severe
      alveolar bone resorption was seen in LPS-injected animals. Administration of
      SD282 significantly blocked additional volumetric bone loss in the LPS-only
      versus LPS + SD282 groups (0.37 +/- 0.01 BVF versus 0.43 +/- 0.01 BVF; P < 0.01).
      Significant reductions in IL-1beta (P < 0.01 ), TNF-alpha (P < 0.05), and
      osteoclast formation (P < 0.01) occurred in the presence of SD282. CONCLUSIONS:
      An orally active p38 MAPK inhibitor reduced LPS-induced inflammatory cytokine
      expression, osteoclastogenesis, and alveolar bone loss in rats. Within the limits
      of the current study, SD282 arrested periodontal disease progression, thus
      highlighting the therapeutic potential of this novel class of inhibitors.

PMID- 18062122
TI  - Effects of TGF-beta1, PDGF-BB, and IGF-1 on the rate of proliferation and
      adhesion of a periodontal ligament cell lineage in vitro.
AB  - BACKGROUND: Considering the role of growth factors in periodontal regeneration,
      the aim of this study was to evaluate the influence of platelet-derived growth
      factor (PDGF)-BB, insulin-like growth factor (IGF)-1, and transforming growth
      factor-beta 1 (TGF-beta1), alone or in combination, on the rate of proliferation
      and adhesion of periodontal ligament (PDL) cells in vitro. METHODS: After
      establishment and characterization of a primary culture of PDL cells, 72 culture
      dishes were plated with 10(3) cells distributed among four test groups and a
      control group. Test groups had PDGF-BB, TGF-beta1, IGF-1, or a combination of all
      three added to the culture medium, whereas the control group received no growth
      factor. The samples were counted in triplicate 1, 3, 5, and 7 days after seeding.
      For the adhesion assay, 14 patients provided 30 root fragments distributed among
      10 groups: scaling and root planing (SRP), SRP + growth factors, SRP + citric
      acid plus tetracycline (CA+T), and SRP + (CA+T) + growth factors. The data were
      evaluated statistically by analysis of variance complemented by Tukey, Dunnett,
      and Student-Newman-Keuels methods. RESULTS: Maximum rates of proliferation were
      observed at day 3 for all groups. TGF-beta1 induced a 344.17% +/- 58.80%
      increased proliferation rate over control (P < 0.05), followed by the combination
      (277.5% +/- 29.38%), PDGF-BB (238.79% +/- 5.79%), and IGF-1 (233.16% +/- 19.19%).
      Groups treated by (CA+T) showed increased numbers of cells attached to root
      fragments, especially SRP + (CA+T) + combination (13.25 +/- 1.79), with
      significant differences (P < 0.05) from groups treated only by SRP. CONCLUSION:
      This combination of growth factors stimulated a mitogenic response and favored
      the adhesion of PDL cells in vitro, suggesting its possible role in periodontal
      regeneration.

PMID- 18062123
TI  - Esthetic treatment of gingival melanin hyperpigmentation with Er:YAG laser: short
      term clinical observations and patient follow-up.
AB  - BACKGROUND: Recently, the erbium-doped:yttrium, aluminum, and garnet (Er:YAG)
      laser has been applied effectively for periodontal soft tissue management. The
      purpose of this study was to report removal of gingival melanin pigmentation
      using an Er:YAG laser in a short-term clinical observation. METHODS: Five
      patients with gingival melanin pigmentation participated in this study.
      Irradiation was performed at 64.0 mJ/pulse (8.5 J/cm2 per pulse) and 10 Hz under
      water spray in contact mode. Clinical parameters, such as bleeding, swelling,
      redness, and healing, were evaluated immediately after the surgery and 24 hours,
      1 and 4 weeks, and 3 months later. A visual analog scale was used to evaluate the
      pain level experienced. RESULTS: The Er:YAG laser effectively ablated the
      epithelial tissue containing melanin pigmentation. At 1 week, gingiva showed fast
      epithelization with a healthy appearance in all cases. At 2 weeks, gingiva showed
      satisfactory healing with significant improvement in color and recovery of the
      tissue thickness. At 1 month, complete healing was observed; after the 3-month
      evaluation, no gingival deformity or recession was observed. However, there was a
      slight recurrence in one case. CONCLUSION: Removal of gingival melanin
      pigmentation can be performed safely by Er:YAG laser resulting in an esthetically
      significant improvement of gingival discoloration.

PMID- 18062124
TI  - Fibrin adhesive derived from snake venom in periodontal surgery.
AB  - BACKGROUND: A new fibrin adhesive made of buffalo plasma-derived fibrinogen and a
      thrombin-like enzyme obtained from snake venom was evaluated in this case series
      with regard to its applicability in periodontal surgery. Free gingival grafts
      that were sutured (control group) were compared to others immobilized through the
      use of the adhesive (experimental group). METHODS: The grafts were carried out in
      contralateral mandibular bicuspids of 15 patients so that each subject received
      one treatment of each type. The analysis included measurements of probing and
      vertical dimension of the grafts and photographic follow-up for 90 days. The
      patients answered a questionnaire concerning postoperative signs and symptoms.
      RESULTS: The decrease in the vertical dimension of the grafts was significant
      during the first 30 days and more dramatic for the control group. Probing depth
      and attachment level presented statistically significant decreases for both
      groups. The grafts of the experimental group presented better appearance during
      the first 14 postoperative days. Pain was observed more often in the control
      group. CONCLUSIONS: Within the limits of the present study, it is suggested that
      the alternative fibrin adhesive tested may represent an alternative to sutures in
      periodontal surgery. Nevertheless, randomized clinical trials should be performed
      to evaluate the clinical advantages and disadvantages of the material.

PMID- 18062125
TI  - Minimally invasive antral membrane balloon elevation: report of 36 procedures.
AB  - BACKGROUND: The posterior maxillary segment frequently has insufficient bone mass
      to support dental implants. This registry evaluated the feasibility and safety of
      minimally invasive antral membrane balloon elevation (MIAMBE), followed by bone
      augmentation and implant fixation. METHODS: Thirty-six consecutive patients
      referred for posterior maxillary bone augmentation underwent alveolar crest
      exposure and implant osteotomy followed by MIAMBE (> 10 mm). Fibrin and bone
      particles were injected beneath the antral membrane, implants were placed into
      the osteotomies, and primary closure was executed at the same sitting. RESULTS:
      All 36 patients successfully concluded the procedure with no significant
      procedural complications or discomfort. Procedure time was 48 +/- 15 minutes.
      Incremental bone height consistently exceeded 8 mm, and implant survival of 97%
      was observed at 6 to 8 months. CONCLUSIONS: MIAMBE resulted in high procedural
      success and satisfactory bone augmentation implant survival and complication
      rates. Because it is minimally invasive, this procedure may be an alternative to
      the currently used surgical methods.

PMID- 18062126
TI  - Vertical guided bone regeneration with bioabsorbable barriers.
AB  - BACKGROUND: Guided bone regeneration (GBR) is a very useful surgical technique to
      increase limited alveolar bone for implant placement. The use of non-resorbable
      barriers is well established; however, bioabsorbable collagen membranes may
      simplify the surgical technique and make it more predictable. METHODS: Vertical
      ridge augmentation was performed on 11 patients at the time of implant placement.
      The part of the implant out of bone was covered with autogenous bone/graft, and a
      slow-resorption collagen membrane was placed on top. Gingival tissues were closed
      with horizontal mattress and interrupted sutures. Second-stage surgery was
      performed 4 to 6 months later, and healing abutments were placed. The length of
      the implant out of bone was determined at stage 1 and stage 2 surgeries on a
      periapical x-ray 1 year after implant load. Histology was obtained from one of
      the cases at second-stage surgery. RESULTS: Measurements revealed that the mean
      implant out of bone was 3.5 mm at stage 1 and 0.5 mm at stage 2. Mean bone gain
      was 3 mm, which represented 83% of the exposed implant at stage 1. One year after
      loading, implants showed a mean marginal bone loss of 1.4 mm. Minimal
      complications were detected, and only one case failed. Histology from one
      successful case showed new trabecular bone with large cellular marrow spaces in
      the regenerated area. CONCLUSION: Slow-resorption collagen membranes have the
      potential to promote vertical ridge augmentation when used with autogenous bone
      at the time of implant placement.

PMID- 18062127
TI  - Successful management of aggressive periodontitis by regenerative therapy: a 3
      year follow-up case report.
AB  - BACKGROUND: This case report presents a new treatment for localized aggressive
      periodontitis using surgery (papilla preservation technique [PPT]) combined with
      enamel matrix proteins and bioactive glass. METHODS: Eight intrabony defects in a
      19-year-old woman with localized aggressive periodontitis were treated by PPT and
      the application of enamel matrix proteins or enamel matrix proteins in
      combination with bioactive glass. Probing depth, gingival recession, and clinical
      attachment level (CAL) were evaluated at baseline, 6 and 12 months, and 2 and 3
      years after treatment. The primary outcome variable was CAL. RESULTS: After 3
      years, the sites treated with enamel matrix proteins demonstrated a mean CAL
      change from 8.3 +/- 3.2 mm to 4.0 +/- 3.6 mm (P < 0.39), and the sites treated
      with enamel matrix proteins combined with bioactive glass showed a mean CAL
      change from 8.6 +/- 2.4 mm to 3.7 +/- 0.8 mm (P < 0.001). CONCLUSION: In the
      present case of aggressive periodontitis, application of enamel matrix proteins
      with or without the addition of bioactive glass resulted in the successful
      treatment of intrabony defects.

PMID- 18062128
TI  - Subepithelial connective tissue graft for root coverage: a case report of an
      unusual late complication of epithelial origin.
AB  - BACKGROUND: The subepithelial connective tissue graft (SCTG) is one of the most
      used and predictable periodontal plastic surgery procedures; reports of late
      complications are very rare. This article presents an SCTG case with a previously
      unreported late complication of epithelial origin, and we suggest a potential
      link between the patient's dermatologic condition and this complication. Late
      SCTG complications also are reviewed. METHODS: A 19-year-old female presented
      with a 3-mm deep Miller Class I recession defect on the mandibular right central
      incisor. An SCTG procedure was performed for root coverage, with uneventful
      initial postoperative healing that resulted in complete root coverage. At 4
      months, an asymptomatic solid white discharge was observed at sites along the
      original graft margin without evidence of inflammation. A month later, the
      somewhat reduced but still evident discharge was collected and submitted for
      microscopic examination. RESULTS: Cytologic examination revealed the discharge to
      be normal epithelial cells, suggesting a proliferative epithelial response.
      Follow-up indicated that the discharge was self-limiting and was no longer
      present at 9 months after surgery. This unusual late SCTG complication is
      consistent with reported epithelial invaginations and projections between graft
      and overlying flap. The patient had acne, a disease whose pathogenesis includes
      host predisposition to epithelial hyperproliferation; therefore, a possible
      association of this SCTG complication with the patient's systemic health is
      proposed. CONCLUSION: Epithelial cell discharge is a hitherto unreported, self
      limiting, late complication of the SCTG procedure, and a potential association
      between this complication and the patient's dermatologic condition is suggested.

PMID- 18062129
TI  - Anorganic bone matrix retrieved 14 years after a sinus augmentation procedure: a
      histologic and histomorphometric evaluation.
AB  - BACKGROUND: Anorganic bone matrix (ABM) is reported to have osteoconductive
      properties. No inflammatory or adverse responses have been reported when this
      material is used in sinus augmentation procedures. ABM is said to be a
      bioabsorbable biomaterial, but histologic data seem to suggest that the
      resorption process is slow. Long-term histologic data in humans are lacking. The
      aim of this case report was to evaluate the bone response to ABM used in
      maxillary sinus augmentation and retrieved 14 years after surgery. METHODS:
      Titanium dental implants were inserted in two sinuses augmented with ABM. The
      implants were osseointegrated and functioned well for 14 years. After this period
      of loading, the connecting screw of one of the implants inserted in the left
      maxilla broke, and it was necessary to remove the implant. A bone core of the
      augmented area was harvested separately during the implant removal. RESULTS: A
      very high quantity of mature, compact bone and a small percentage of residual
      grafted biomaterial were found. About 5% to 7% of the bone was undergoing
      remodeling. In most cases, residual ABM particles were surrounded by marrow
      spaces. In other areas, lamellar bone was found in tight contact with the
      particle surfaces. Histomorphometry showed that the mean amount of mature,
      compact bone was 71.0% +/- 2.28%, the mean amount of ABM was 22.1% +/- 3.18%, and
      the mean amount of marrow spaces was 11.2% +/- 5.42%. CONCLUSIONS: ABM seemed to
      resorb very slowly; after 14 years, only a small quantity of residual grafted
      particles was present. ABM is an effective graft material for sinus augmentation
      procedures. Vital, mature bone was formed and maintained over a long period with
      no chronic inflammatory cell infiltrate, foreign body response, or other adverse
      effects.

PMID- 18062130
TI  - [[Evidence-based medicine or hocuspocus, What is there in probiotics?].

PMID- 18062131
TI  - [In adolescents smoking is more prevalent as ever before. Way to early death].

PMID- 18062132
TI  - [The legs of a diabetic patient].

PMID- 18062133
TI  - [General physician's advice to those traveling abroad: prescriptions for every
      possible emergency].

PMID- 18062134
TI  - [Sunscreens for UV protection and repellants--who needs what?].
AB  - If UV injury of the skin is to be avoided, sun protection by clothing and
      sunscreen according to the skin type must be employed. Protection against insect
      stings and bites is provided not only by clothing and mosquito nets but also by
      suitable repellants, which will depend on the place visited and the user's age.

PMID- 18062135
TI  - [Exhibition "Deadly Medicine" in Dresden. German medicine inclusive eugenics and
      "end solution"].

PMID- 18062136
TI  - The bioactive nature of human breastmilk.
AB  - Human breastmilk is widely accepted to be the optimal source for nutrition for
      the newborn infant, containing all the proteins, lipids, carbohydrates,
      micronutrients and trace elements required for growth, development and immune
      protection. In addition human breastmilk plays a significant role in the
      prevention of medical conditions such as childhood cancers, obesity and
      gastrointestinal diseases. The importance of breastmilk and its superiority as a
      source of infant nutrition is highlighted in the recent overhaul of teh World
      Health Organization growth charts that are now based on exclusively breastfed
      infants. Human breastmilk also contains a population of cells, the importance of
      which is often not considered when the bioactivity of breastmilk is discussed.

PMID- 18062137
TI  - All night long: understanding the world of infant sleep.
AB  - An understanding of the complex physiological, neurological and psychological
      world of the infant is important in order to provide recommendations about the
      sensitive and consistent care needed for optimal development. However, when it
      comes to the subject of infant sleep, professional and lay resources are often
      based on misinformation and misunderstanding of developmental stages and needs.
      In order to provide a holistic and scientific foundation for understanding infant
      sleep, this paper outlines normal infant sleep mechanisms, development and
      patterns as defined by the literature. Biopsychological data is also presented to
      demonstrate the study of infant stress, attachment and caregiving routines used
      to engage infants in sleep. This information can be used as a guideline for
      determining which sleep choices and approaches are healthy for infants and those
      which discourage optimal development and leave infants and families at risk.

PMID- 18062138
TI  - A systematic review of measures assessing mothers' knowledge, attitudes,
      confidence and satisfaction towards breastfeeding.
AB  - In order to support breastfeeding interventions, there is a need for objective,
      reliable, valid and sensitive measures of factors related to breastfeeding.
      Publications on the development and testing of tools measuring mothers'
      knowledge, attitudes, confidence or self-efficiency and/or satisfaction towards
      breastfeeding were systematically reviewed. Twenty-two papers evaluating 13 self
      report measures matched our selection criteria, and were critically appraised by
      two independent reviewers. All scales were tested with pregnant women or
      breastfeeding mothers. The 13 measures varied markedly in ease of completion and
      cultural appropriateness and none reached our highest level of evidence grading.
      Four of the measures had sufficient evidence to support their use, including the
      Breastfeeding Attrition Prediction Tool, the Modified Breastfeeding Evaluation
      Scale, the Breastfeeding Self-Efficiency Scale and the Iowa Infant Feeding
      Attitude Scale. There has been a tendency to develop new measures rather than
      evaluate the strengths and weaknesses of existing measures, particularly in
      different populations.

PMID- 18062139
TI  - Determinants of blood pressure among Indonesian elderly individuals who are of
      normal and over-weight: a cross sectional study in an urban population.
AB  - Cardiovascular disease has become the first cause of death in Indonesia. The
      highest morbidity is found in the aged, and among cardiovascular disorders or
      diseases, the prevalence of hypertension is the highest. Many studies of the
      relationship between nutritional factors and hypertension have been conducted,
      especially with reference to the metabolic syndrome, but studies to understand
      determinants of blood pressure in Indonesia are lacking. There is an urgent need
      to gather information about various blood pressure risk factors in Indonesian
      elderly, which will allow policy makers to provide appropriate intervention
      programs. The primary purpose of this study was to investigate various
      determinants of blood pressure in Indonesian elderly using multistage random
      sampling. Data were collected through interview using structured questionnaires,
      anthropometric measurements, biochemical blood analysis, and blood pressure
      measurements. Daily nutrient intake was analyzed using the World Food 2 Dietary
      Assessment Program. General Linear Model and Multiple linear regression analysis
      were performed to determine determinants of systolic and diastolic blood
      pressure. Monounsaturated fatty acid, saturated fatty acid, and sodium intake,
      plasma total cholesterol level, the ratio of total cholesterol to HDL-cholesterol
      and a sport Index were determinants of blood pressure in the normal weight
      elderly individuals, while potassium intake, calcium intake and BMI were
      determination of blood pressure in the overweight elderly individuals.

PMID- 18062140
TI  - Extracorporeal life support in severe propranolol and verapamil intoxication.
AB  - Combined poisoning with calcium-channel blockers and beta-blockers is usually
      associated with severe heart failure. This report shows the effectiveness of
      emergency extracorporeal life support in treating life-threatening simultaneous
      propranolol and verapamil intoxication. A 15-year-old girl presented in
      cardiogenic shock after alcohol consumption and a propranolol and verapamil
      overdose; plasma concentrations: propranolol, 0.53 m/mL; verapamil, 1.06 mg/mL.
      She was successfully resuscitated with extracorporeal life support. Therapeutic
      plasma exchange was initiated. Extracorporeal support was discontinued 70 hours
      later. The patient made a full recovery. Simultaneous verapamil and propranolol
      overdoses can cause severe hemodynamic compromise and arrest of electrical and
      mechanical function of the heart. Emergency extracorporeal life support can
      successfully maintain vital organ blood flow and allows time for drug metabolism,
      redistribution, and removal. Therapeutic plasma exchange may reduce the time of
      emergency extracorporeal life support. Emergency extracorporeal life support
      should be considered early in cases of near-fatal intoxications with
      cardiodepressive drugs.

PMID- 18062141
TI  - Human papillomavirus (HPV) vaccines: a Canadian update.
AB  - A common sexually transmitted infection, human papillomavirus (HPV) has been
      linked to the development of cervical, anogenital, and head and neck cancers and
      genital warts. (2) Several randomized controlled trials have explored the
      efficacy and safety of two vaccines for primary prevention of infection by HPV
      types 16 and 18, those most commonly implicated in the development of cervical
      cancer. (3) An HPV vaccine, Gardasil, was approved in Canada in 2006, and a
      second vaccine, Cervarix, is undergoing Health Canada review. (4) Some unresolved
      questions about HPV vaccinations relate to the ideal age for immunization,
      duration of effect, immunization of women already infected, vaccination of males,
      implications for Papanicolaou (Pap) smear programs, barriers to uptake, need for
      monitoring and registries, cost effectiveness, and programs to ensure access for
      special populations.

PMID- 18062142
TI  - Proceedings of the 9th International Symposium on Yersinia, October 10-14, 2006,
      Lexington, Kentucky, USA.

PMID- 18062143
TI  - ELIPPSE 65-80 study.
AB  - This longitudinal study implemented within the framework of Canceropole PACA and
      financed on call for tender by the National Institute of the Cancer is the first
      study in France concerning the psychosocial impact of the breast cancer at women
      of more than 65 years.

PMID- 18062144
TI  - Where the wild things are: wayward birds and other animals can land in
      practitioners' laps.

PMID- 18062145
TI  - Adnexal torsion, a medical complication of in vitro fertilization.
AB  - With the expanding use of assisted reproductive technologies, general
      obstetricians and gynaecologists must maintain a high index of suspicion for
      complications of in vitro fertilization. We present the case of a pregnant woman
      with unilateral adnexal torsion following in vitro fertilization and its
      diagnostic implications in an emergency setting.

PMID- 18062146
TI  - [Colorectal cancer--CT, MRI diagnosis and surgery].

PMID- 18062147
TI  - Tuft cells.
AB  - Tuft cells, also known as brush cells, are widespread in the hollow organs of the
      digestive tract including the duct system of the salivary gland and in the
      respiratory tract, from simple vertebrates to humans. The shape of tuft cells
      varies from pear-shaped, to barrel-shaped and goblet-shaped, apparently depending
      on the plane of section. The most characteristic morphological features of tuft
      cells are their long and blunt microvilli, which have prominent rootlets, and a
      well developed tubulovesicular system in the supranuclear cytoplasm. Both the
      microvilli and tubulovesicular system can be labeled with lectin and periodic
      acid-thiocarbohydrazide-silver proteinate-physical development (PA-TCH-SP-PD),
      suggesting a relationship between them. Many spheres observed among the
      microvilli seem to originate from the head of a polyp-like structure protruding
      into the vesicles, suggesting some type of apocrine secretion. During mammalian
      development, tuft cells increase around the time of weaning as neonates gradually
      become accustomed to solid food. Tuft cells in the rat gallbladder and stomach
      possess intermediate filaments, that is, neurofilaments and cytokeratin-18
      filaments. Despite numerous morphological studies, the functions of tuft cells
      are still obscure. The discovery of the presence of alpha-gustducin has provided
      a clue to the long-sought function of tuft cells, which appear to possess the
      cellular and molecular basis for chemoreception. The present review discusses the
      three currently proposed functions of tuft cells--secretory, absorptive and
      receptive--on the basis of morphological, histochemical and cytochemical
      evidence.

PMID- 18062148
TI  - Apoptosis and the insulin-like growth factor family in the developing olfactory
      epithelium.
AB  - Vertebrate olfactory receptor neurons (ORN) are unique in that they are
      continually replaced throughout life. They die by apoptosis under physiological
      conditions at all stages during the life cycle, and apoptotic ORN are replaced by
      their progenitor cells. Apoptosis is linked with neurogenesis, of which pathway
      is regulated by a number of growth factors and neurotrophic factors. Members of
      the insulin-like growth factor (IGF) family have an anti-apoptotic effect on ORN,
      in addition to their ability to promote the proliferation, differentiation, and
      survival of these neurons. Expression of IGF and related molecules at both mRNA
      and protein levels in the olfactory epithelium have been reported. In this review
      article, we focus on apoptosis, IGF, and their related molecules in the
      developing olfactory epithelium.

PMID- 18062149
TI  - Morphological and morphometric evaluation of lacrimal groove.
AB  - The nasolacrimal canal is placed at the anterior part of the inferior lateral
      wall of the orbit and opens to the inferior nasal meatus. The canal can be
      obstructed by acquired diseases such as dacryocystitis and posttraumatic epiphora
      due to nasoorbitoethmoidal fractures. Furthermore in nasolacrimal canal
      obstructions, dacryocystorhinostomy with balloon dilatation is used frequently.
      In evaluation of the nasolacrimal canal's acquired diseases, obstruction
      etiologies and during the reopening of the canal with balloon dilatation, knowing
      the lacrimal groove's morphology and morphometry play an important role. The aim
      of the present study was to evaluate not only the morphological features and
      types but also the morphometric measurements of lacrimal groove. A total of 60
      (30 right, 30 left) adult human dry bone maxillae (both male and female samples)
      from the collection of the Department of Anatomy of Dokuz Eylul University
      Medical School were used. Digital compass with 0.01 mm sensitivity was used for
      measurements. Average length of lacrimal groove was 9.62 +/- 2.10 mm. Average
      width of lacrimal groove was 5.88 +/- 1.53 mm at upper one-third, 8.04 +/- 2.05
      mm at middle one-third, and 5.94 +/- 1.28 mm at lower one-third. In 87.7% of
      cases a crista was observed at the end of the lacrimal groove. Among them, 34.0%
      were directed to inferior, 54.0% were directed to posterior and 12.0% were
      horizontal. The present results on the width, length, shape and direction of the
      lacrimal groove could mediate the etiology of nasolacrimal canal obstructions and
      could be helpful in surgical approaches and clinical treatment.

PMID- 18062150
TI  - Prenatal stress induces learning deficits and is associated with a decrease in
      granules and CA3 cell dendritic tree size in rat hippocampus.
AB  - Exposure to gestational stress impairs hippocampal-dependent learning in
      offspring. In spite of the known decisive role of hippocampal dendritic
      architecture in learning and memory, there has been no study to date that
      examines the effect of prenatal stress on the morphology of the hippocampal
      neurons. Therefore we performed a quantitative morphological analysis of the
      dendritic architecture of Golgi-impregnated hippocampal neurons in prenatally
      stressed rats. Subjects included male rat offspring (2 months old) for which the
      mothers had been restrained for 1 h/day during the last week of gestation.
      Spatial learning performance levels using Morris water maze and changes in the
      morphology of hippocampal dendritic trees were studied. Results indicated that
      the study group had lower spatial learning capabilities along with decreased
      length and number of dendritic segments, branching of granules and cornu ammonis
      (CA)3 pyramidal cells. There was no change in the dendritic morphology of CA1
      pyramidal cells. These results suggest that prenatal stress in rat results in
      spatial learning deficits and profound alterations in the neurites of the
      hippocampal cells of male offspring.

PMID- 18062151
TI  - Fascicular analysis at perineurial level of the branching pattern of the human
      common peroneal nerve.
AB  - The macroscopic branching pattern of the peripheral nerves is usually provided by
      the epineurial connective tissue, whereas the removal of the epineurium discloses
      component fascicles covered by a perineurial sheath comprising a fine network
      with a peculiar branching pattern. In order to compare both patterns, the common
      peroneal nerve (PC) was dissected minutely in 10 human legs. At the epineurial
      level the branching pattern into tributary bundles was variable in respect to
      both the origin of the superficial peroneal nerve and that of the muscular
      branches (Rr. m. peroneus longus, RPL) to the peroneus longus. At the perineurial
      level the fascicles formed intricate tiny plexuses without a discrete branching
      pattern, but as a whole consisted of a regular arrangement divided into four
      crural streams for the deep peroneal (PP), the accessory deep peroneal (PPA) and
      two dorsal cutaneous nerves. The RPL fascicles were derived substantially from
      the PPA stream. The findings on the fascicular branching pattern in the present
      study show that the PC consists of two muscular and two sensory streams that were
      ensheathed by the epineurium to form the PP containing a single muscular stream,
      and the superficial peroneal nerve with the three remaining streams. Thus the
      extensor and peroneal muscles of the leg have their own nerve supply from the PP
      and PPA, respectively. The branching pattern of the fascicles of muscular
      branches at the perineurial level may be a useful estimator of muscle grouping,
      for which the branching pattern at the epineurial level is hardly of any use due
      to its variability.

PMID- 18062152
TI  - Developmental changes in pulpal sensory innervation of rat incisors and molars
      shown on a single injection of the fluorescent dye AM1-43.
AB  - Developmental changes in pulpal innervation of rat incisors and molars were
      examined using the fluorescent styryl dye AM1-43, which labels sensory cells and
      nerves in vivo. From 2 to 40 days after birth, the animals were injected once
      with a small amount of AM1-43 solution (2 microg/g bodyweight). One day after the
      injection, the animals were killed and examined. In 3-day-old rats, neither
      incisors nor molars were innervated. In 7-day-old rats, the pulp of incisors and
      molars was innervated as indicated by fine intensely stained varicose sensory
      fibers and thicker intensely stained fibers running mostly along the blood
      vessels. In 15-, 27-, and 41-day-old rats, sensory nerve fibers neither passed
      through the odontoblast layer nor penetrated into the dentin in incisors, whereas
      the sensory nerve fibers penetrated into the coronal dentin through the
      odontoblast layers in molars. These results suggest that innervation of dental
      pulp is composed of two phases: (i) linear penetration of nerve fibers along
      blood vessels into the pulp space; and (ii) sprouting and extension of nerve
      fibers into coronal dentin. Innervation of the incisor pulp may stop at the first
      phase.

PMID- 18062153
TI  - Raymond de Vieussens.
AB  - Raymond de Vieussens provided significant insight into more than one area of
      medicine and opened up the field of research for decades to come. Raymond de
      Vieussens was born in France and graduated with his medical doctorate in 1670
      from the University of Montpellier. After graduation Vieussens was appointed as
      physician to the hospital of Saint Eloys in Montpellier. At the beginning of his
      career Vieussens' work was well received in the European medical community and is
      heralded as the most complete account of the brain, spinal cord and peripheral
      nerves to emerge in the 17th century. In 1706, Vieussens published Nouvelles
      Decouvertes sur le Coeur, in which he presented detailed anatomy of the lymphatic
      system and blood vessels of the heart. Vieussens' observations on the heart were
      expanded in 1715 with the publication of Treatise of the Heart. In this treatise
      Vieussens described the pericardium, coronary vessels and muscle fibers of the
      heart in detail. His work also included the first documented clinical
      presentations and autopsy results of patients with mitral valve stenosis and
      aortic valve insufficiency. Vieussens' 1715 Treatise of the Heart was heralded as
      one of the most important discussions on the correlation between clinical
      symptoms of heart disease and the anatomical basis for these findings. The legacy
      of Vieussens persists today via the multiple eponyms attributed to his initial
      descriptions.

PMID- 18062154
TI  - Bilaterally existing sternoclavicularis anticus muscles.
AB  - A 92-year-old Japanese woman was found to have the sternoclavicularis anticus
      muscles existing bilaterally during the course of educational dissection at
      Nagoya City University Medical School. It was confirmed that these muscles
      received the nerve supply from small branches of the lateral pectoral nerves from
      the brachial plexus. Herein is documented the precise gross anatomical findings
      with some morphometric measurements. Moreover, the morphology of this muscle is
      discussed in relation to previously described variations of the pectoral sheet of
      muscles.

PMID- 18062155
TI  - Anomalous venous system in the human heart.
AB  - In a 2002 cadaveric dissection course, a complex manner of rare variation was
      found in the abnormal venous system of the heart of an 88-year-old Japanese man
      who died of acute pneumonia. The superior vena cava and the left and right
      brachiocephalic veins were normal. In this case, a complex venous system existed
      as follows. (1) A left superior vena cava was persistent. (2) The innominate vein
      was present. It went upward between the ascending aorta and the pulmonary trunk,
      passed through the ventral side of the bifurcation of the pulmonary trunk, and
      then anastomosed with the left superior vena cava. The oblique vein of the left
      atrium, as a fibrous bundle, was connected to the junction of the left superior
      vena cava and the innominate vein in the pericardium. (3) The great cardiac vein
      was divided into two branches. One was located at the right side of the left
      coronary artery, forming the origin of the innominate vein. The other extended to
      the coronary sinus as a normal great cardiac vein. (4) The orifice of the
      coronary sinus on the right atrium was obliterated. (5) The abnormal orifice
      existed between the left atrium and the coronary sinus. The formation process and
      functional significance of such venous variations are discussed.

PMID- 18062156
TI  - [Unexpected loss of therapeutic effect of oxcarbazepine].
AB  - After months of successful analgesic therapy with oxcarbazepine, a 52-year old
      woman with trigeminal neuralgia suddenly experienced episodes of heavy trigeminal
      attacks regularly in the evening at about the same time. Asked about changes in
      daily life or eating habits, she reported the ingestion of healing earth daily in
      the morning. After stopping the ingestion of healing earth, analgesic control of
      trigeminal neuralgia was restored without any changes of the initial
      pharmacotherapy. In daily practice, interactions which significantly influence
      the absorption of drugs are often overlooked. The documentation of these
      interactions in drug interaction databases, in the prescribing information, and
      in the literature is sparse though clinically relevant. Separating the ingestion
      of interacting substances by a time interval may not sufficiently avoid the
      interaction in every case. Particular caution is warranted when slow-release
      cation containing drugs or substances with entero-hepatic circulation are used.

PMID- 18062157
TI  - [Functional gastrointestinal disorders].
AB  - Functional gastrointestinal disorders particularly dyspepsia an irritable bowel
      syndrome are frequent problems for the general practitioner and also for the
      specialist. Both are diseases and not only a kind of discomfort. The high
      frequency of dispepsia and irritable bowel syndrome induces very high direct and
      indirect charges. Both diseases depend on a number of factors or causes, for whom
      the evidence is not good. But there are good experimental data for the visceral
      hypersensitivity as one of the main factors. Gastroscopy is the most important
      examination in the diagnosis of dyspepsia. Endoscopy has to be done in all
      patients with alarm symptoms an in all patients older than 45 years. The therapy
      of dyspepsia is an empirical one. The eradication of Helicobacter pylori is a
      therapeutical option, but only 8% of the patients will have benefit for a long
      time. Other therapeutical options are the use of proton-pump inhibitors,
      prokinetics or phytotherapeutics. The therapy of the irritable bowel syndrome
      depends on the subtype of the disease (diarrhea, constipation, abdominal pain,
      bloating). First of all a good doctor-patient relationship is mandatory.
      Furthermore the use of dietary fibre, antidiarrhoeics, laxatives and muscle
      relaxants may be beneficial. And phytotherapeutics can be an additional
      therapeutic approach.

PMID- 18062158
TI  - [Non-alcoholic steatohepatitis--a new epidemic].
AB  - Non-alcoholic steatohepatitis (NASH), the metabolic syndrome of the liver,
      characterised by the consequences of obesity (insulin resistance, production of
      free radicals, chronic inflammation) has become a new epidemic in the United
      States as in Europe. Diagnosis is suspected in patients with obesity, denying
      alcohol abuse, having typical co-morbitities (Hypertension, Diabetes mellitus,
      Hyperlipidemia). Liver histology confirms the diagnosis of NASH. Fatty liver
      without inflammation bears a good prognosis. Liver fibrosis, however, in NASH
      patients signalizes progression to liver cirrhosis and even HCC. Treatment
      modalities are limited. Reduction of body weight, physical activity, treatment of
      co-morbitities, specially Hypertension and Diabetes are of paramount importance.
      At the moment it remains unclear whether glitazone treatment could be introduced
      in the therapeutic armentarium.

PMID- 18062159
TI  - [Indication for terminal sedation].

PMID- 18062160
TI  - [21-year-old patient with left side chest pain and pleural effusion].

PMID- 18062161
TI  - [Posterior capsule opacification (PCO) following implantation of various types of
      IOLs--part one: the uncomplicated course].
AB  - PURPOSE: Despite of decreasing incidence of the PCO, this is still a major and
      frequent complication of cataract surgery and IOL implantation. Therefore, in our
      Department, we pay currently intense attention to the PCO problem. The
      introduction of EAS 1000 in October 2001 allowed us to analyze exactly the
      relevant PCO issues and our attitude toward its treatment as well. The purpose of
      our study was to compare the PCO degree in eyes with implanted either PMMA IOLs
      with round edges or hydrophilic acrylate IOLs with sharp edges. Four types of
      IOLs were compared in our trial. MATERIALS AND METHODS: In the Department of
      Ophthalmology, Comenius University and Faculty Hospital, Bratislava, Slovakia,
      the PCO development was analyzed in patients operated on due to senile cataract
      between November 14th 2001 and April 10th 2003. Eighty-two eyes of 77 patients
      were followed-up from November 2001 till April 2006. During the 36 months' follow
      up, 82 eyes of 77 patients were enrolled in this study. We evaluated the PCO at
      day 1, week 1 and 3, 6, 12, 24, and 36 months after the cataract surgery. In all
      patients, the best visual acuity was assessed. The photographs of the posterior
      capsule in retro-illumination in the widest possible mydriasis were obtained and
      evaluated by means of EAS 1000. RESULTS: Our study revealed significant influence
      of the optic material and the type of the implant edge on the PCO development. We
      did not find any correlation between the visual acuity and the transparency of
      the posterior capsule. The incidence of Nd:YAG-laser capsulotomies was similar in
      the two compared IOL groups (PMMA round edged vs. hydrophilic acrylate sharp
      edged IOLs). We also did not find any correlation between the size of area
      evaluated and the posterior capsule transparency. CONCLUSION: In our experience,
      EAS 1000 (NIDEK) has proved to be a suitable device for the follow up of the PCO
      development following various IOLs types implantation in both experimental and
      clinical setting. Standardized and objective evaluation systems based bn the
      retro-illumination photography are needed. Despite a certain possibility of
      examiner-related error of measurement, EAS 1000 (NIDEK) is an accurate device for
      PCO evaluation.

PMID- 18062162
TI  - [Opacification of hydrophilic acrylic intraocular lenses].
AB  - The authors present results of retrospective study of 10 cases of Aqua-Sense
      hydrophilic acrylic intraocular lens (IOL) explantation performed during the
      calendar year 2005 at the Department of Ophthalmology, University Hospital,
      Hradec Kralove, Czech Republic. The preoperative visual functions, perioperative
      findings and postoperative results were evaluated. The best corrected visual
      acuity (BCVA) before explantation was surprisingly good, even in cases with
      severe opacification of the lens. There were no serious perioperative
      complications; in 9 cases, the stable capsular bag enabled us to implant the new
      IOL in the bag or in the sulcus. In one case, the suction of the secondary
      cataract was done. In one eye, the zonular dehiscence developed, and the new IOL
      was placed into the anterior chamber (angle supported AC IOL). We did not see any
      postoperative complications. The BCVA improved in 3 eyes, in 7 eyes the BCVA
      remained the same. All patients were satisfied with the postoperative results.
      Histopathological examinations of the explanted IOLs showed multiple tiny calcium
      granules concentrated in continuous narrow band closely beneath the anterior
      surface of the optic part of the IOL. The postoperative calcification of some
      currently available hydrophilic acrylic IOLs is one of the common reasons for IOL
      explantation/exchange. Sophisticated surgical techniques greatly improved the
      postoperative results.

PMID- 18062163
TI  - [Spherical covering foil--silicone implant forming conjunctival fornices].
AB  - METHOD: The authors refer about primary development of elastic and sufficiently
      strong device, which due to its spherical shape bandages the conjunctival space
      of the palpebral fissure and is used to form the inferior and superior cul-de
      sac. It is made from a silicone mixture for medical use - Silastic Medical Grade
      Elastomer. Its layer in the shape of spherical cap of outer diameter 24.4 mm,
      height 8.5 mm; the layer thickness is 0.5 mm. Its advantage is the oxygen
      permeability. RESULTS: The spherical covering foil was applied as an arrangement
      before keratoplasty in four adult men to form fornices after relieving of
      symblephara reaching the cornea caused by alkali (lime) burn (in three of them)
      and after liquid aluminium burn (thermal injury). In five years old boy, the
      spherical covering foil helped to form the palpebral fissure and to improve the
      eye motility; the symblepharon was related to the inborn coloboma of the upper
      eyelid. To prevent the symblepharon appearance, the spherical covering foil was
      used in an adult man after molten polypropylene burn and in an eight years old
      boy with Stevens - Johnson syndrome. CONCLUSION: The spherical covering foil is
      used for cul-de-sac forming after relieving of the symblepharon or to prevent its
      appearance after the eye burn.

PMID- 18062164
TI  - [Correlation of the Heidelberg retinal tomograph, evaluation of the retinal nerve
      fiber layer and perimetry in the diagnosis of glaucoma].
AB  - PURPOSE: To assess the correlation of the selected structural and functional
      methods in the diagnosis of glaucoma. METHODS: The study group (SG) of 40
      patients with primary open angle glaucoma with no or early visual field changes
      was compared to the control group (CG) of 40 healthy persons of similar age in
      the first year of prospective longitudinal study. All participants underwent the
      examination by means of Heidelberg retinal tomograph, photography of retinal
      nerve fiber layer, standard white-on-white perimetry, and blue-on-yellow
      perimetry. Only one eye of each examined person was evaluated. Significance was
      assessed by means of non-parametric test (Mann-Whitney) and the correlation
      analysis (Spearman) was performed as well. RESULTS: No significant differences in
      age, visual acuity, and refraction between SG and CG were found. The central
      corneal thickness (p< 0.05) and intraocular pressure (p< 0.01) were significantly
      different between both groups. The visual field mean sensitivity (MS) and mean
      defect (MD) of white-on-white perimetry differ significantly between SG and CG
      comparing to the visual field parameters of blue-on-yellow perimetry. HRT
      analysis found out significant parameters: cup area (CA), cup/disc ratio (C/D),
      rim/disc ratio (R/D), and rim volume (RV) (p< 0.05). Cup shape measure (CSM) and
      Mikelberg discrimination function (FSM) were significant as well (p< 0.01). The
      loss of retinal nerve fiber layer was significantly different (p< 0.01) between
      the glaucomatous and healthy eyes. Spearman's correlation analysis found out
      significant correlations (MS and MD) only in blue-on-yellow perimetry and CV and
      RV of HRT analysis by comparison of all healthy and glaucomatous eyes. Another
      significant correlations were found by comparison of the retinal nerve fiber
      layer loss to MS (p = 0.00) and MD (p = 0.03) of white-on-white perimetry. Some
      of HRT parameters: CA, RA, CD, RV, CSM, HVC and RNFL in the group of all 80 eyes
      were significantly correlated to retinal nerve fiber layer loss. In the group of
      glaucomatous eyes only, no significant correlations were found. CONCLUSION:
      Combination of the structural and functional methods can positively improve
      diagnosis of early glaucoma and better recognize the progression of glaucomatous
      neuropathy of the optical nerve.

PMID- 18062165
TI  - [Changes of the thickness of the ciliary body after the latanoprost 0.005 %
      application].
AB  - In a randomized prospective open study the authors followed up the influence of
      latanoprost 0.005 % on the changes of the ciliary body thickness by means of
      ultrasound biomicroscopy. The study group consisted of 40 eyes of 24 patients
      with primary open angle glaucoma not treated with latanoprost before. At the
      entry visit and further after 2 and 8 weeks, according to the study protocol, a
      complex ophthalmologic examination was performed; especially anatomical relation
      between the cornea and the iris, configuration of the anterior chamber angle, and
      furthermore the best visual acuity for far and near, intraocular pressure
      measurement by means of applanation method, anterior chamber depth, and the pupil
      size. The thickness of the ciliary body was measured in the distance of 1,500
      microm (T1), 2,000 microm (T2), and 2,500 microm (T3) from the scleral spur. A
      slight decrease of T1 comparing with the initial values was found: from 668 +/-
      117 microm in the beginning, to 633 +/- 127 microm after two weeks, and 614 +/-
      147 microm after eight weeks of treatment. In the case of T2 measurement, the
      situation is similar; the decrease of the values was smaller than in T1. The
      above-mentioned differences were not statistically significant. Practically no
      differences were found in the T3 measured values. The intraocular pressure during
      the follow-up decreased markedly - from 21.3 +/- 4.2 mm Hg to 18.8 +/-3.3 mm Hg
      (week 2) and 17.6 +/- 3.7 mm Hg (week 8). The average lowering of the intraocular
      pressure (IOP) by 2.5 mm Hg (i.e. by 11.7%) found between the initial values and
      values after two weeks of treatment was found as statistically significant (P
      value = 0.0001) as well as the difference between the initial values and values
      after eight weeks of treatment. No statistical significant difference was found
      between IOP values measured after two and eight weeks of treatment. All other
      followed-up parameters (anterior chamber depth, size of the pupil, visual acuity,
      and external finding) remained during the eight weeks period unchanged. Our
      results are in the congruity with one of hypotheses of the latanoprost acting -
      compacting of the interstitium and following opening of the porosities among the
      muscles fibers bundles of the ciliary body cause the increase of the intraocular
      fluid outflow and marked decrease of the intraocular pressure. To explain the
      mechanisms affecting the ciliary body in detail, more studies are needed.

PMID- 18062166
TI  - [Dry eye syndrome in rheumatoid arthritis patients].
AB  - The aim of this cross-sectional study was to review the incidence of the dry eye
      syndrome in rheumatoid arthritis (RA) patients, evaluate the association among
      the incidence of the dry eye syndrome, presence of positive rheumatoid factor
      (RF), the RA stage, and the duration of the disease. The group consisted of
      altogether 100 patients, 16 men and 84 women; the average age was 58.9 years (SD
      14.6). The average duration of RA was 12.3 years, SD 11.0. In each patient, the
      Schirmer test I was performed, the presence of the LIPCOF (Lid Parallel
      Conjunctival Folds) on the slit lamp was assessed, the BUT (Tear Break-Up Time)
      was measured and vital fluorescein staining was performed. In each patient the
      data of the presence or absence of the RF in the serum, RA severity according to
      the X-ray examination, and the disease duration were recorded. The Pearson's
      association test for nominal variables was used for statistical evaluation of the
      association between the rheumatoid arthritis presence and the dry eye syndrome.
      In our group of 100 patients, the Schirmer test I was positive in 67% of
      patients. Positive BUT was marked in 84 % of patients. The conjunctival folds
      were present in 45 % of patients only. The pathological findings after cornea
      fluorescein staining appeared in 18 % of patients. The dry eye syndrome incidence
      was marked in 74% of patients with RA. Subjective difficulties were declared by
      38.3% of patients only. The local treatment was already established in 23.0% of
      patients only. We did not find statistically significant correlation between the
      RF positive rheumatoid arthritis appearance and dry eye syndrome, nor between the
      stage of the rheumatoid arthritis and presence of the dry eye syndrome. We proved
      statistical connection between the presence of dry eye syndrome and the duration
      of rheumatoid arthritis longer than 10 years. Keratoconjunctivitis sicca is the
      most common ocular complication in rheumatoid arthritis patients. We proved the
      connection between the dry eye syndrome presence and duration of the RA longer
      than 10 years; we did not find the dependence among the RF presence and stage of
      the rheumatoid arthritis and the appearance of the dry eye syndrome. The early
      diagnosis of the dry eye syndrome and the effective local therapy may prevent
      very serious corneal complications, which are difficult to treat.

PMID- 18062167
TI  - [Diabetics in population of patients treated by pars plana vitrectomy].
AB  - The purpose of this study is to evaluate visual and anatomic outcomes following
      pars plana vitrectomy (PPV) for complications of diabetic retinopathy (DR), and
      to assess risk factors that might influence the visual outcome after successful
      PPV. The medical records of 35 diabetic patients of both types 1 and 2 of
      diabetes, who underwent vitrectomy for complications of proliferative diabetic
      retinopathy (PDR) between 2004 and 2005, were analyzed retrospectively. Certain
      preoperative systemic and ophthalmic variables, intraoperative variables and
      postoperative complications with negative influence on visual outcome after PPV
      were recorded. The postoperative follow-up time was 6 months. The collected data
      as well as visual outcomes after PPV were statistically analyzed. Statistically
      significant visual improvement was achieved in 51.4 % of the patients; visual
      acuity (VA) deteriorated in 25.7% of the patients and remained unchanged in 22.9
      % of the patients. Preoperative median of VA was 0.0167, changed to 0.1
      postoperatively and remained stable on 0.1 level during the 6 months follow-up.
      VA > or = 0.1 was achieved in 60 % of the patients 6 months after PPV. Some of
      the followed variables associated with deteriorated or unchanged postoperative VA
      can be considered as risk factors of an unfavorable prognosis. Evaluated risk
      factors include preoperative VA worse than 0.1, presence of systemic
      complications of DM accompanying ocular complications, postoperative occurrence
      of iris neovascularization and neovascular glaucoma. In conclusion, anatomically
      successful PPV in diabetic patients is not always followed by an improvement of
      VA. The optimal timing of vitrectomy is very important not only in order to
      obtain good visual acuity but also to maintain good visual function for long
      time. We suppose that an adequate control of DM, sufficient screening for DR and
      timely laser intervention of DR might decrease the progression of DR and onset of
      sight threatening complications of PDR as well as decrease the prevalence of
      blindness at diabetic patients in the future.

PMID- 18062168
TI  - Parkinsonism induced by chronic manganese intoxication--an experience in Taiwan.
AB  - Excessive manganese exposure may induce a neurological syndrome called manganism,
      which is similar to Parkinson's disease (PD). However, close observation of
      patients with manganism reveals a clinical disease entity different from PD, not
      only in the clinical manifestations, but also in therapeutic responses, in
      neuroimaging studies such as magnetic resonance imaging, positron emission
      tomography and dopamine transporter images, and in the neuropathological
      findings. Furthermore, after long-term follow-up studies, patients with manganism
      showed prominent deterioration in the parkinsonian symptoms during the initial 5
      10 years, followed by a plateau during the following 10 years, which is also
      different from the clinical course of patients with PD. Although typical patients
      with manganism are different from patients with PD, the potential risk of
      inhaling welding fumes, which may accelerate the onset of PD or even induce PD,
      has been raised during recent years. This controversial topic requires further
      investigation.

PMID- 18062169
TI  - Vitamin B6 related epilepsy during childhood.
AB  - In some patients without vitamin B6 deficiency, epilepsy can not be controlled
      without an extra supplement of vitamin B6. The therapeutic role of pyridoxal
      phosphate (PLP), the active form of vitamin B6, may not be replaced with other
      forms of vitamin B6 sometimes. Until now, four inborn errors of metabolism are
      known to affect vitamin B6 concentrations in the brain. Three of them are
      hyperprolinemia type 2, antiquitin deficiency, and pyridoxine phosphate oxidase
      deficiency. The fourth disorder occurs in neonates with hypophosphatasia and
      congenital rickets. All patients with these conditions present with early-onset
      epilepsy that is resistant to conventional antiepileptic medications. Patients
      with three of the conditions respond to any form of vitamin B6. Only those with
      pyridoxine phosphate oxidase deficiency respond to PLP instead of pyridoxine.
      Interestingly, the authors have successfully treated many patients without the
      above four disorders using vitamin B6, and have found that the treatment was more
      effective with PLP than with pyridoxine, though the mechanism is not known. Since
      PLP is as inexpensive as pyridoxine, we suggest replacing PLP for pyridoxine when
      treating children with epilepsy.

PMID- 18062170
TI  - Isolation and differentiation of human mesenchymal stem cells obtained from
      second trimester amniotic fluid; experiments at Chang Gung Memorial Hospital.
AB  - BACKGROUND: The aims of this study were to evaluate the efficacy of current
      techniques for isolating mesenchymal stem cells (MSCs) from amniotic fluid
      obtained by second-trimester amniocentesis as well as to determine their
      differentiation potential. METHODS: We collected 50 samples of amniotic fluid by
      second-trimester amniocentesis. To obtain MSCs from amniotic fluid, the fluid was
      cultured using the two-stage culture protocol described in previous literature.
      Reverse transcription-polymerase chain reaction (RT-PCR) of a stem cell-specific
      transcription factor, octamer-binding protein 4 (Oct-4), was used to identify the
      characteristics of the MSCs cultured from amniotic fluid. Osteogeneic
      differentiation of these MSCs was confirmed by the presence of osteocalcin (a
      mineral-binding protein uniquely synthesized by osteoblasts) using RT-PCR and Von
      Kossa staining. Adipogenic differentiation of these MSCs was displayed by RT-PCR
      of adipocyte lipid-binding protein (a lipid-binding protein specifically in
      adipocytes) and Oil Red O staining. RESULTS: Amniotic fluid-derived MSCs were
      successfully isolated and cultured from six samples. These cells could express
      the pluripotent stem cell-specific transcription factor Oct-4 as confirmed by RT
      PCR. Under specific culture conditions, amniotic fluid-derived MSCs could be
      successfully induced to differentiate into adipocytes and osteocytes, based on
      product analysis by RT-PCR and specific staining. CONCLUSION: Based on our
      experiment, we estimate the efficacy of isolating mesenchymal stem cells from
      second-trimester amniotic fluid obtained by amniocentesis to be about 12%. Human
      MSCs from second-trimester amniotic fluid had the ability to differentiate in
      vitro into adipocytes and osteocytes under specific culture conditions. The
      multilineage differentiation potential of these amniotic fluid-derived MSCs may
      be applicable to cell transplantation and regenerative medicine.

PMID- 18062171
TI  - Associations between brain-derived neurotrophic factor G196A gene polymorphism
      and clinical phenotypes in schizophrenia patients.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) had been chosen as a
      candidate gene for schizophrenia. This study investigated the relationships
      between BDNF G196A gene polymorphism and clinical phenotypes in schizophrenia
      patients in the Taiwanese population. METHODS: During a one year period, 132
      schizophrenic patients and 103 healthy controls were recruited. Psychiatric
      diagnoses were made according to DSM-IV criteria. Genotyping of the G196A
      polymorphism of BDNF was performed by polymerase chain reaction amplification and
      restriction fragment length polymorphism. RESULTS: The data showed that the BDNF
      G196A genotypes and their allele distributions did not differ between patients
      with schizophrenia and healthy controls. No significant differences were noted in
      the BDNF G196A genotypes and allele distribution between schizophrenia patients
      with and without a family tendency for schizophrenia or between those with an age
      of onset before or after 25 years old. However, there was a significant
      difference in BDNF G196A genotype distribution between schizophrenia patients
      with and without a suicide history. CONCLUSIONS: These analytical results suggest
      that BDNF G196A gene polymorphism is associated with a susceptibility to a
      suicide history in schizophrenia patients in the Taiwanese population. Further
      study with a larger number of samples is needed to prove these findings.

PMID- 18062172
TI  - Conditions affecting treatment of pertrochanteric osteomyelitis.
AB  - BACKGROUND: Although osteomyelitis following treatment of pertrochanteric
      fractures is rare, management can be difficult and often results in several
      physical and economic difficulties. Data regarding treatment of patients with
      pertrochanteric osteomyelitis is currently limited. This retrospective study
      evaluates the management of pertrochanteric osteomyelitis and presents our
      experience using a two-stage treatment protocol. METHODS: From 1984 to 1998,
      twenty-three pertrochanteric osteomyelitis cases were treated with a two-stage
      protocol comprising of an external skeletal fixator or Buck traction after
      radical debridement in the first stage and reconstruction in the second stage.
      The study included sixteen males and seven females with a mean age of 48.3 years
      (range 16-82 years). Patients were categorized as "successful" or "difficult"
      according to the number of operations they had undergone. Conditions including
      patient age, compromised host, interval before treatment, fracture severity,
      nonunion, hip joint involvement, multiple organisms and the presence of oxacillin
      resistant Staphylococcus aureus were recorded for analysis. RESULTS: Only twelve
      of the twenty-three (52%) cases were successfully managed and infection recurred
      in four (17.4%) cases at final follow-up. Difficult cases managed by the two
      stage protocol were more likely to be characterized by younger age (p = 0.03),
      unstable fractures (p = 0.003) and nonunions (p = 0.027). CONCLUSION: The use of
      external skeletal fixation is not recommended for managing pertrochanteric
      osteomyelitis. Success using a two-stage protocol was difficult to achieve.
      Initial fracture severity should be carefully assessed when devising a treatment
      protocol for pertrochanteric osteomyelitis.

PMID- 18062173
TI  - Clinical characteristics of children with learning disorders in Taiwan.
AB  - BACKGROUND: Clinical studies of children with learning disorders (LD) in Chinese
      speaking society are still very limited. The aim of this study was to obtain the
      clinical picture of children with LD in Taiwan. METHODS: Medical records of
      diagnoses-validated subjects in a local children's hospital from 1998 through
      2005 were reviewed in detail. Relevant data were collected and analyzed. The
      diagnoses were made based on the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for learning
      disorders. RESULTS: Among the 27 subjects (23 boys and 4 girls) identified, the
      average age upon diagnosis was 9.6 +/- 2.0 years with school grade of 3.5 +/-
      1.9. The percentages of subjects with reading disorders (RD), mathematics
      disorders (MD) and disorders of written expression (DWE) were 66.7%, 11.1% and
      77.8%, respectively. Over half (55.6%) of the subjects had two subtypes
      concurrently, and the majority of which had both RD and DWE. The overall,
      psychiatric, and medical comorbid rates were 88.9%, 81.5% and 22.2%,
      respectively. Attention-deficit/hyperactivity disorder (ADHD) was the most common
      (66.7%) co-existing condition. Subtypes were slightly different in terms of
      demographic data, IQ profile and comorbid conditions. CONCLUSIONS: Our LD sample
      was predominantly male with average levels of intelligence and highly comorbid
      with ADHD. Each subtype of LD seemed to have its own unique feature in terms of
      cognitive function, comorbid condition, sexual differences, and other aspects.
      Further research is eagerly warranted. When evaluating learning problems,
      clinicians should keep in mind that ADHD often exists. Treating concomitant ADHD
      and other co-existing problems should bring more favorable outcomes. Due to the
      heterogeneity of LD, evaluation of each suggested case should be carefully
      monitored and individually tailored.

PMID- 18062175
TI  - The use of Charlson comorbidity index for patients revisiting the emergency
      department within 72 hours.
AB  - BACKGROUND: To validate the use of the Charlson Comorbidity Index (CCI) for
      predicting admission of patients revisiting the Emergency Department (ED) within
      72 hours. METHODS: Non-trauma patients aged above 17 years old who revisited an
      urban ED within 72 hours during January of 2004 were included in this
      retrospective observational study. Demographic data, diagnosis, CCI, in-hospital
      mortality rate and length of hospital stay were reviewed, and comparisons were
      made between the patients who were admitted or discharged on their return visits.
      RESULTS: Of the 168 enrolled patients, 60 were admitted to a ward and 108 were
      discharged. Revisiting patients with high CCIs (> or = 2) had a higher admission
      rate (67.3% vs. 22.7%; p < 0.001) and an increased adjusted odds ratio of
      admission (odds ratio (OR) 2.06; 95% confidence interval (CI) 1.14-3.75) than low
      CCI patients. Admitted revisiting patients with high CCIs had poorer prognoses,
      longer hospital stays (11.79 +/- 8.92 days vs. 6.78 +/- 5.17 days; p < 0.05) and
      a higher in-hospital mortality rate (15.2% vs. 3.7%; p = 0.209). CONCLUSION: CCI
      was well correlated with the admission possibility of patients revisiting the ED
      within 72 hours. More clinical management and discharge strategies should target
      those revisiting patients who have more comorbidities.

PMID- 18062174
TI  - Comparison of outcomes of velopharyngeal surgery between the inferiorly and
      superiorly based pharyngeal flaps.
AB  - BACKGROUND: Pharyngeal flaps have been widely used for the correction of
      velopharyngeal incompetence. The aim of this study was to compare the outcomes of
      velopharyngeal surgery between those who received the superiorly and inferiorly
      based pharyngeal flaps. METHODS: A retrospective review of medical records of
      patients with cleft palates who received pharyngeal flap surgery for the
      correction of velopharyngeal incompetence at one craniofacial center was
      performed. The superiorly based flaps were elevated and inset using the fish
      mouth method. The inferiorly based flaps were sutured to the soft palate where a
      distally based mucosa flap was turned over to cover the raw surface of the flap
      pedicle. The velopharyngeal functions were categorized as adequate, marginal, or
      inadequate. Complications associated with the operation were documented.
      Statistical comparisons between the two groups were made. RESULTS: There were 65
      patients in each group. No statistically significant differences were found for
      sex distribution and age at operation. The outcomes of the velopharyngeal surgery
      were better in the group of patients who received the inferiorly based pharyngeal
      flaps (p = 0.030). The complications were not significantly different between the
      two groups, and were all relatively mild. CONCLUSION: The inferiorly based
      pharyngeal flap was more effective than the superiorly based pharyngeal flap for
      the correction of velopharyngeal incompetence. A probable explanation may be the
      fibrotic changes and scar contracture occurring in the pedicle of the superiorly
      based pharyngeal flap that may have impaired the velopharyngeal closure.

PMID- 18062176
TI  - The association between embrasure morphology and central papilla recession: a
      noninvasive assessment method.
AB  - BACKGROUND: The distance from bone crest to contact point is only the most
      frequently studied of the many factors that influence whether interdental papilla
      are present. The purpose of this study was to discover the association between
      embrasure morphology and central papilla recession. METHODS: The central papilla
      was visually assessed in 310 adults using paralleling periapical radiographs of
      the maxillary central incisors. The following vertical distances were measured:
      the recession distance, i.e., papilla tip (PT) to contact point (PT-CP), bone
      crest (BC) to contact point (BC-CP), proximal cementoenamel junction (pCEJ) to
      contact point (pCEJ-CP), papilla height (PH), and bone crest to proximal
      cementoenamel junction (BC-pCEJ). Interdental width was measured horizontally.
      Subjects were divided into 4 groups according to interdental width and pCEJ-CP
      distance: long-narrow, short-narrow, long-wide, and short-wide. RESULTS:
      Statistical analysis revealed the following for all four study groups: a positive
      correlation between papilla recession distance and age, a positive correlation
      between bone crest-contact point distance and age, and a negative correlation
      between age and papilla height. CONCLUSION: Central papilla recession as a result
      of aging occurs most frequently in the long-wide group, that is, among people who
      have both a wide interdental width and a long distance between the proximal
      cementoenamel junction and the contact point. However, other factors also affect
      the likelihood of central papilla recession. Thus, there is a need for further
      study of the interaction among these causal factors.

PMID- 18062177
TI  - Acute unilateral parotid glands enlargement following endotracheal general
      anesthesia: report of two cases.
AB  - Acute parotid gland enlargement in association with general anesthesia is rare
      and has also been called anesthesia mumps. We present two patients who were
      scheduled for lumbar spine surgery under general anesthesia. Each developed acute
      unilateral parotid gland enlargement over one side of the face proven by
      sonography. Case 1: A 52-year-old man was scheduled for his third lumbar spine to
      first sacral spine surgery for scoliosis and spondylolisthesis. The patient was
      provided general anesthesia with oral endotracheal intubation and placed in the
      prone position with the neck flexed at approximately 10 degrees. The head was
      turned to the left side and the right side of the face was placed on a soft gel
      rolling pad. After 6 hours of surgery, swelling of the right parotid gland was
      noted upon endotracheal extubation. Twenty four hours later, the patient received
      sonographic examination of the salivary gland which showed dilatation of the
      right parotid duct with obstructive inflammation. After receiving non-steroidal
      anti-inflammatory drug (NSAID) treatment, his symptoms and signs subsided 2 weeks
      after the surgery. Case 2: A 53-year-old woman was scheduled for her third lumbar
      spine to fifth lumbar spine instrumentation and internal fixations for
      spondylolisthesis. A similar anesthetic regimen and surgical position was
      provided as with Case 1. The duration of the surgery was about 5 hours and
      swelling of the right parotid gland was also noted postoperatively. Sonographic
      examination of the salivary gland showed only an inflammatory process without
      dilatation of the parotid duct. She had complete recovery of the condition 10
      days after surgery. There were no complications nor residual enlargement of the
      parotid gland in either of our two patients after conservative treatment.

PMID- 18062178
TI  - Dumbbell-shaped Hodgkin's disease with cauda equina compression mimicking a
      herniated inter-vertebral disc, a case report.
AB  - Hodgkin's disease may involve the spine as a setting of the advanced disease. An
      initial manifestation of Hodgkin's disease in spine is extremely rare and the
      major involved sites usually are the thoracic or cervical spine. The mechanisms
      of pathogenesis for the formation of an epidural mass during Hodgkin's disease
      are hematogenous dissemination from nodal sites or local infiltration of
      lymphomatous tissue. We document here a case of a 16 year-old boy who suffered
      from incomplete voiding due to dumbbell-shaped retroperitoneal Hodgkin's disease
      with cauda equina compression. He was successfully managed using surgery and
      adjuvant chemotherapy. Although lymphadenomatous tissue responds well to
      radiotherapy and chemotherapy, the role of surgery in this case was to achieve
      immediate nerve tissue decompression and to obtain an adequate specimen for
      pathological diagnosis. Magnetic resonance imaging (MRI) is a non-invasive and
      helpful tool when detecting spinal and paraspinal lesions and we emphasize that
      spinal MRI should be performed without delay if there is persistent back pain or
      sciatica.

PMID- 18062179
TI  - Phenotypic and genotypic analysis of Borrelia spp. isolated from Ixodes ricinus
      ticks by using electrophoretic chips and real-time polymerase chain reaction.
AB  - The genotype of Borrelia burgdorferi sensu lato was detected in 371 out of 1244
      ticks. Borrelia determination was based on partial sequencing of the 16S rRNA
      gene and real-time polymerase chain reactions for identification and quantitation
      of ospA and recA genes. Different Borrelia spp. were identified; B. garinii in
      40% ticks followed by B. afzelii (36.3%), B. burgdorferi sensu stricto (12.9%),
      B. valaisiana (3.5%), B. lusitaniae (0.8%), B. bissettii (0.5%) and B. miyamotoi
      like (0.5%). Cultivation of 30 borrelia strains in BSK-H medium, among them B.
      valaisiana, B. bissettii-like and B. miyamotoi-like strains was unique in
      Czechia. Calibrated microfluidic-based quantification showed differences in the
      concentration of the nucleic acids and molar mass of the outer surface proteins
      of different Borrelia spp. with standard sensitivity and specificity and was
      helpful for their identification. The outer surface protein OspA was absent in B.
      miyamotoi-like and the OspB protein in B. valaisiana, B. lusitaniae and in three
      subtypes of B. garinii.

PMID- 18062180
TI  - Piezoelectric immunosensor for the direct and rapid detection of Francisella
      tularensis.
AB  - A novel immunosensing device based on a piezoelectric sensor for direct detection
      of the biological warfare agent Francisella tularensis was developed. This sensor
      includes mouse polyclonal antibody immobilized in a layer of protein A covalently
      linked to the gold electrode of the sensor. The immunosensor is able to detect F.
      tularensis with the limit of detection 10(5) CFU/mL with a typical measuring
      cycle > 5 min. The sensor was successfully evaluated for rapid detection of F.
      tularensis spikes in drinking water and milk; no deterioration of sensitivity in
      comparison with buffer solutions was observed. The proposed concept of a rapid
      measurement of microbial agents seems to be promising for evaluation of samples
      after short pre-cultivation enrichment.

PMID- 18062181
TI  - Genome rearrangements in host-range mutants of the polyvalent staphylococcal
      bacteriophage 812.
AB  - Mutations extended the host range of the polyvalent bacteriophage 812 of the
      family Myoviridae in up to 95 % of Staphylococcus aureus strains and 43 % of
      strains of different coagulase-positive and -negative Staphylococcus species.
      Mutational changes in the genome of several host-range mutants of phage 812 were
      identified. Host-range mutant 812F1 harbors a deletion in endolysin gene that
      arose together with intron excision. Four mutants (812i, 812b, 812p, 812F3)
      harbor deletion in the structural gene orf8 that results from a genome
      rearrangement associated with intron insertion. This rearrangement was also
      detected in the genome of the closely related phages U16 and phi131. Another
      intron was discovered in the recA812 gene in these four mutants. An insertion was
      found in a non-coding region of the restriction fragment PstI-O of three mutants
      (812b, 812F3, 812g) and phages U16 and phi131. The above results contribute to
      the explanation of genetic factors affecting the host range of polyvalent
      staphylococcal bacteriophages.

PMID- 18062182
TI  - Detection of lateral heterogeneity in the cytoplasmic membrane of Bacillus
      subtilis.
AB  - Lateral heterogeneity in the cytoplasmic membrane of Bacillus subtilis was found
      by using density gradient centrifugation. Crude membranes (CM) present in the
      whole cell lysate were separated into three fractions of increasing density (F,
      CI, CII). Substantial difference exists in the amount of protein recovered from
      these fractions, the relative ratio being 15 : 35 : 50. The qualitative protein
      composition (by SDS-PAGE) of the fractions varies markedly as well. The lipid
      components extracted from the fractions are also distributed in different
      proportions, viz. 40 : 40 : 20. The spectrum of fatty acids (FA), detected in
      lipids of F fraction and analyzed by GC-MS exhibits the same profile as that
      found in CM; in contrast, fractions CI and CII undergo extensive FA
      reconstruction. Thermotropic behavior of fractions measured by the steady-state
      fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene indicates significant
      variations of microviscosity (r(s)) within the F, CI and CII fractions. The
      protein-to-lipid ratio plays evidently a key role in affecting the physical state
      of the cytoplasmic membrane. Microdomains of different density coexist in the
      membrane and exhibit heterogeneity in both chemical composition and "physical
      state"; the increased de novo synthesis of FA induced by the cold exclusively in
      fractions CI and CII indicates correlation with an altered physiological state of
      bacterial metabolism.

PMID- 18062183
TI  - Complete genome sequence and analysis of the Streptomyces aureofaciens phage
      mu1/6.
AB  - The entire double-stranded DNA genome of the Streptomyces aureofaciens phage
      mu1/6 was sequenced and analyzed. Its size is 38.194 kbp with an overall molar
      G+C content of 71.2 %. Fifty-two potential open reading frames (orfs) were
      identified, divided into two oppositely transcribed regions. In the left arm of
      the mu1/6 genome, an identified putative integrase and possible regulation
      proteins were identified. The rightwards transcribed region contains genes
      organized into apparently four functional units responsible for: (i) replication,
      (ii) DNA packaging and head assembly, (iii) tail morphogenesis, and (iv) lysis.
      Putative functions were assigned to twelve orfs based on bioinformatic analysis
      or experimental substantiation. Comparative analysis with three complete genomes
      of streptomycete phages revealed resemblance with respect to the organization of
      their genes into functional modules. Closer relationship was observed only
      between mu1/6 and S. venezuelae phage VWB.

PMID- 18062184
TI  - Multiple regulatory genes in the salinomycin biosynthetic gene cluster of
      Streptomyces albus CCM 4719.
AB  - A DNA fragment containing part of the salinomycin biosynthetic gene cluster from
      industrial strain Streptomyces albus CCM 4719 was cloned. Sequence analysis of
      the 25.809-kbp fragment revealed the presence of 8 open reading frames (ORFs),
      including two large ORFs encoding three modular sets of oligoketide synthase,
      followed by three genes (salRI, salRII, salRIII) encoding transcriptional
      regulators. The first two regulators, SalRI and SalRII, belonged to the novel LAL
      family of large transcriptional regulators. SalRIII was highly similar to the
      NysRIV, AmphRIV, and FscRI transcriptional regulators from the oligoene
      macrolides nystatin, amphotericin, and R008/candicidin clusters, respectively.

PMID- 18062185
TI  - Adaptation of adhesion test using Caco-2 cells for anaerobic bacterium
      Pseudobutyrivibrio xylanivorans, a probiotic candidate.
AB  - Pseudobutyrivibrio xylanivorans strain Mz5(T), an anaerobic bacterium
      (originating from the rumen of a Holstein-Friesian cow), has some attributes that
      make it a possible probiotic strain (very active hydrolases, bacteriocin and
      conjugated linoleic acid production). For the estimation of its adhesion ability,
      the adhesion test on Caco-2 cells was introduced and adapted. The adhesion was
      performed in an anaerobic glove box in standard 24-well plates at neutral pH for
      30 min. The best method for separation of the adhered bacteria from Caco-2 cells
      appeared to be homogenization with an automatic pipette. The number of adhered
      bacteria was too small to be determined microscopically, so a new approach, i.e.
      detection of the apparent lag phase in liquid growth medium was tested. Under the
      selected assay conditions 1.04 bacterial cells from the late exponential phase
      adhered to one Caco-2 cell, which confirms the adhesion capability of P.
      xylanivorans Mz5(T). The adapted adhesion test using Caco-2 cells is suitable for
      estimation of adhesion capability of anaerobic bacteria.

PMID- 18062186
TI  - Ribotyping and biotyping of Staphylococcus epidermidis isolated from hospital
      environment.
AB  - The Staphylococcus strains acquired from scrapings from hospital environments
      were identified to the species level based on their biochemical properties. From
      the monitored sample the Staphylococcus epidermidis strains were selected for
      more accurate typing and tested on their virulence factor and ribotyped. The
      biotyping of S. epidermidis did not show any considerable intraspecific variation
      of these isolates and there were no atypical reactions, with the exception of
      three strains (out of 33). In contrast, the results of ribotyping showed greater
      heterogeneity of strains and unequivocally demonstrated the relation between the
      ribotype and the place of sample drawing. In addition to this fact, the found
      ribotypes repeat in the same environment in the long-term which suggests the
      occurrence and persistence of the same strains of conditionally pathogenic
      bacteria in hospital environment. We showed that ribotyping is a suitable method
      for precise and reliable detection of some coagulase-negative staphylococci.

PMID- 18062187
TI  - Alterations in mitochondrial morphology of Schizosaccharomyces pombe induced by
      cell-death promoting agents.
AB  - The effect of the yeast cell-death inducing agents, Bax and acetic acid, on
      mitochondrial structure of Schizosaccharomyces pombe was studied. Comparison of
      mitochondrial structures in cells grown on different substrates and visualized
      with different probes revealed variations in their morphology. Cells grown on
      respiratory C sources as well as in the presence of antimycin A exhibited
      punctuated mitochondria when visualized with mitochondrially targeted green
      fluorescent protein, while they still appeared as tubular structures when stained
      with DiOC6(3). Both expression of Bax and acetic acid treatment induced
      fragmentation and aggregation of mitochondrial network, which could be prevented
      by coexpression of Bcl-XL. Aberrant mitochondrial morphology generated by either
      Bax or acetic acid was not accompanied with the loss of mitochondrial genome
      (mtDNA), indicating that alterations of mitochondrial morphology following death
      stimuli follow different mechanisms than those involved in mitochondrial
      inheritance mutants.

PMID- 18062188
TI  - Production, purification and oxidative folding of the mouse recombinant prion
      protein.
AB  - The method leading to overexpression of the full-length mouse recombinant prion
      protein (mrPrP 23-231) in the cytoplasm of E. coli as a his-PrP fusion protein
      and its effective purification using affinity chromatography is described. A
      typical yield of the method was 8-10 mg his-mrPrP per L of the bacterial culture.
      The purity of purified protein was > 95 %. The purified his-mrPrP was converted
      to a soluble form and its folding to alpha-helical and beta-sheet conformations
      was studied. The properties of differently folded mrPrP were determined by
      measuring their circular dichroism spectra, partial resistance to cleavage by
      proteinase K and by centrifugation in sucrose gradient.

PMID- 18062189
TI  - Growth, survival and reproduction in Chlorella vulgaris and C. variegata with
      respect to culture age and under different chemical factors.
AB  - Batch cultures of Chlorella vulgaris and C. variegata reproducing about twice
      every 5 d within 0-15 d had vegetative cells and autospore mother cells in the
      ratio of about 19 : 1. Continuous slow or negligible and/or no growth in > 15-d
      old control cultures or in young cultures supplied with the antibiotics
      streptomycin, penicillin, amoxycillin (10-1000 ppm) or tetracycline (10, 100
      ppm), and pesticides carbofuran, gammaxine, moticop or iralon (1-100 ppm) was due
      to slow autospore mother cells dehiscence (leading to an increase in their
      percentage); while negligible and/or no growth of both algal species in sewage
      water (100, 25%), detergent (0.1-1%), petrol or kerosene (5-20 %), benzene,
      toluene or phenol (5, 10%) and pesticides rogor or endosulfan (1, 10 ppm) was due
      to vegetative cells failure to differentiate into auto-spore mother cells
      (leading to decreased/zero autospore mother cells percentage) and/or rapid death
      of all cells. C. variegata was equally or slightly more sensitive to different
      chemical stress than C. vulgaris.

PMID- 18062190
TI  - Intracellular colonization of Rhododendron and Vaccinium roots by Cenococcum
      geophilum, Geomyces pannorum and Meliniomyces variabilis.
AB  - Four in vitro experiments were set up to verify the colonization potential of
      ectomycorrhizal (EcM) Cenococcum geophilum FR. (strain CGE-4), saprotrophic
      Geomyces pannorum (LINK) SIGLER & CARMICHAEL (GPA-1) and a frequent root
      associated, potentially ericoid mycorrhiza (ErM)-forming Meliniomyces variabilis
      Hambleton & Sigler (MVA-1) in roots of Rhododendron and Vaccinium. A typical ErM
      fungus, Rhizoscyphus ericae (Read) Zhuang & Korf (RER-1), was included for
      comparison. All fungal strains intracellularly colonized rooted Vaccinium
      microcuttings: GPA-1 occasionally produced hyphal loops similar to ErM, MVA-1 and
      RER-1 exhibited a typical ErM colonization pattern. CGE-4 hyphae grew vigorously
      on and around newly formed roots and rarely penetrated turgescent rhizodermal
      cells forming intracellular loose loops. Rooting of Rhododendron sp.
      microcuttings was not promoted by any fungal strain except CGE-4, which also
      promoted the most vigorous growth of Rhododendron ponticum L. seedlings. The
      widespread EcM fungus C. geophilum has a potential to colonize non-EcM roots and
      support their development which may influence overall growth of ericaceous
      plants. As shown for G. pannorum, structures resembling ErM may be formed by
      fungi that are to date not regarded as ericoid mycorrhizal.

PMID- 18062191
TI  - Influence of mineral and organic fertilization on soil fungi, enzyme activities
      and humic substances in a long-term field experiment.
AB  - Changes in microfungal communities, fungal activities and humic substances (HS)
      in agricultural soils kept under different fertilization regimes were observed
      and their causal relationships were investigated in a long-term field experiment.
      Fertilization did not change the abundance of HS-utilizing microfungi and, except
      for organic amendment alone, total culturable microfungi were also unaffected by
      this factor. Organic fertilization increased activities of manganese peroxidase
      (MnP) and proteinase, but decreased endo-1,4-beta-glucanase activity compared to
      the corresponding control without organic fertilization. In soils treated with
      mineral fertilizers, the activities of MnP, endo-1,4-beta-glucanase and
      proteinase were higher than in control without any mineral treatment. Both the
      aromaticity of fulvic acid and the molar mass of humic acid was lower in soil
      with organic fertilization, which may be a result of oxidative degradation
      mediated by higher MnP activity observed in treatments with organic
      fertilization.

PMID- 18062192
TI  - Biodegradation of chlorpyrifos by Klebsiella sp. isolated from an activated
      sludge sample of waste water treatment plant in Damascus.
AB  - A chlorpyrifos (CPY)-degrading bacterial strain was isolated from an activated
      sludge sample collected from the Damascus Wastewater Treatment Plant, Syria. The
      isolation of Klebsiella sp. was facilitated by the addition of CPY at a rate of
      3.84 g/L of sludge weekly (selection pressure). Identification of Klebsiella sp.
      was done using major staining and biochemical differentiation tests (Gram stain,
      cytochrome oxidase and some relevant saccharide fermentation tests using
      biochemical assays). Klebsiella sp. was maintained by culturing in a poor medium
      consisting of mineral salts and CPY as the sole carbon source. When 3 activated
      sludge samples were incubated in the presence of CPY (13.9 g/L sludge), 46% of
      added CPY were degraded within 4 d. By comparison, within 4 d the isolated
      Klebsiella sp. was found to break down 92% of CPY when co-incubated in a poor
      mineral medium in which CPY was the sole carbon source (13.9 g/L poor medium).
      Isolated Klebsiella sp. was able to tolerate up to 17.3 g of CPY in the poor
      medium.

PMID- 18062193
TI  - Influence of subinhibitory concentrations of amikacin and ciprofloxacin on
      morphology and adherence ability of uropathogenic strains.
AB  - The influence of subinhibitory concentrations (1/2, 1/4, 1/8, 1/16 and 1/32 MIC)
      of amikacin and ciprofloxacin on the morphology and adherence of uropathogenic
      strains was studied. Intensity of morphological changes was proportional to the
      concentrations of these antibiotics. Morphological changes were the most
      prominent after bacterial exposure to sub-MICs of ciprofloxacin. These
      concentrations, especially 1/2 MIC of ciprofloxacin, induced the formation of
      filaments of E. coli, K. pneumoniae, K. oxytoca, E. cloacae and A. calcoaceticus
      biotype anitratus. No morphological changes were observed in P. aeruginosa, S.
      epidermidis and S. aureus cells after exposure to subinhibitory concentrations of
      both antibiotics. Sub-MICs of amikacin affected the changes in cell shape only
      slightly. The exposure of bacterial strains to 1/2 MIC of ciprofloxacin induced
      increased vacuolation of the cells. We observed shrinkage of the protoplasm and
      the pleated cell walls in comparison with control cells. The greatest loss of
      adherence ability occurred at 1/2 MIC of ciprofloxacin after a 1-d incubation.

PMID- 18062194
TI  - Nucleic acid amplification technique for detection of Chlamydia trachomatis
      infection from clinical urogenital swabs.
AB  - An improved nucleic acid amplification test (NAAT) to detect Chlamydia
      trachomatis infections, based on PCR amplification within its cryptic plasmid
      (CT1/CT2 Test) was developed. DNA was extracted from urogenital swabs and a 594
      bp long DNA fragment from the cryptic plasmid (pCT) was amplified. The
      sensitivity and specificity of the CT1/CT2 Test were determined to be 100 and
      99%, respectively, when directly compared with current amplification kit for
      sexually transmitted diseases (MPCR). Basic epidemiological data related to the
      patients attending gynecological and/or urological clinics are also provided. The
      overall prevalence rate in this group of patients suspected for C. trachomatis
      infection was determined to be about 95 per 1000 (88 and 107 per 1000 in females
      and males, respectively). It demonstrates that the CT1/CT2 Test is suitable for
      epidemiological screening and/or diagnostic practice.

PMID- 18062195
TI  - Molecular detection of Ureaplasma urealyticum infection from clinical urogenital
      swabs.
AB  - A simple nucleic acid amplification test (NAAT) was developed for detection of
      Ureaplasma urealyticum infection based on the PCR amplification of the urease
      gene (UU1/UU2 Test). DNA was extracted from urogenital swabs and a 225-bp long
      DNA fragment was amplified by PCR. NAAT was compared to the commercial
      amplification kit for sexually transmitted disease reference assay. The
      sensitivity and specificity of the UU1/UU2 Test were determined to be 100 and
      98.9%, respectively. The overall prevalence rate in this group of patients was
      found to be about 236 per 1000 (283 and 166 per 1000 in females and males,
      respectively). These data demonstrate that UU1/UU2 Test is suitable for effective
      epidemiological screening and/or diagnostic practice.

PMID- 18062196
TI  - Existence of Sinorhizobium meliloti genomic fragment hybridizing with the nifM
      gene of Klebsiella pneumoniae.
AB  - A novel finding that genomic restriction fragments of symbiotic nitrogen fixer S.
      meliloti hybridized with nifM gene probe of the free-living diazotroph Klebsiella
      pneumoniae is reported. When SmaI endonuclease was used to digest S. meliloti
      DNA, a unique hybridizing band was obtained.

PMID- 18062197
TI  - [Working despite having diseases: Cardiovascular diseases].

PMID- 18062198
TI  - [Working despite having diseases: Digestive system diseases].

PMID- 18062199
TI  - [Working despite having diseases: Respiratory tract diseases].

PMID- 18062200
TI  - [Working despite having diseases: Endocrine and metabolic diseases].

PMID- 18062201
TI  - [Working despite having diseases: Kidney and urologic diseases].

PMID- 18062202
TI  - [Working despite having diseases: Neurological diseases].

PMID- 18062203
TI  - [Working despite having diseases: Hematological diseases].

PMID- 18062204
TI  - [Working despite having diseases: Autoimmune diseases].

PMID- 18062205
TI  - [Working despite having diseases: Infectious diseases].

PMID- 18062206
TI  - [Working despite having diseases: Mental diseases].

PMID- 18062207
TI  - [Working despite having diseases: Musculoskeletal system diseases].

PMID- 18062208
TI  - [Working despite having diseases: Obstetric and gynecologic diseases].

PMID- 18062209
TI  - [Standard for physical examination of aircraft pilots].

PMID- 18062210
TI  - [Clinical study on poor PSA response to initial endocrine therapy with MAB or
      estrogenic drugs for treatment of prostate cancer].
AB  - PURPOSE: The prostate specific antigen (PSA) level usually is lowered in response
      to initial endocrine therapy even in advanced cases of prostate cancer, but in
      some cases, it is not. We examined the cases in which the PSA level was not
      sufficiently lowered by initial endocrine therapy with maximal androgen blockade
      (MAB) or estrogenic drugs. MATERIALS AND METHODS: The subjects were 20 patients
      with prostate cancer diagnosed between January 1992 and December 2005 whose PSA
      level was not lowered below 10 ng/ml after initial endocrine therapy with MAB or
      estrogenic drugs. We investigated the frequency of cases, pretreatment PSA
      levels, PSA nadir levels after initial endocrine therapy and throughout the
      therapy, PSA response to second line therapy, and the prognosis. RESULTS: The PSA
      level was not lowered below 10 ng/ml after initial endocrine therapy with MAB or
      estrogenic drugs in 4.9% of the cases. Cancer-specific survival rates in all
      cases were extremely poor, 75.0% at 1 year and 14.7% at 3 years. Prognosis tended
      to be worse in patients with a higher PSA nadir level throughout the therapy and
      on whom second therapy was not effective, although the difference was not
      statistically significant. CONCLUSION: The patients whose PSA levels were not
      lowered sufficiently by MAB or estrogenic drugs had an extremely poor prognosis.
      These results are useful in planning the therapy, and in explaining the status or
      future prospective of the disease to patients and their families.

PMID- 18062211
TI  - [Evaluation of the effects of microwave tissue coagulation, radiofrequency
      ablation or ultrasonically-activated scalpel on renal tissue as a minimally
      invasive therapy].
AB  - PURPOSE: The objective of this study was to optimize least invasive techniques,
      like microwave tissue coagulation (MCT), radiofrequency ablation (RFA) or
      ultrasonically-activated scalpel (USS) for the electric and thermal conduction in
      kidney. MATERIALS AND METHODS: Needle electrode of MCT, RFA or USS were inserted
      into pig's kidney, under general anesthesia. We examined if the interruption of
      renal artery or cooling of renal parenchyma by irrigation in the renal pelvis had
      an effect on the tissue temperature distribution and area of tissue degeneration.
      The tissue parenchyma temperatures were measured at regular intervals of area
      (each 2.5-5.0 mm) from needle electrode or hook probe and of time (each 10 sec)
      using by needle temperature sensor, and pathological investigations on the tissue
      degeneration of the renal parenchyma were done. RESULTS: By MCT, interruption of
      renal artery had no effect on the distribution of tissue temperature and the area
      of tissue degeneration. Cooling of renal parenchyma by irrigation in the renal
      pelvis did not affect the area of tissue degeneration but the tissue temperature
      was elevated significantly. By RFA, particular interest, interruption of renal
      artery and cooling of renal parenchyma enhanced to increase both the tissue
      temperature and the area of tissue degeneration. By USS, interruption of renal
      artery enhanced to increase both the tissue temperature and the area of tissue
      degeneration. Cooling of renal parenchyma by irrigation in the renal pelvis had
      no effect on the distribution of temperature and the area of tissue degeneration.
      We also examined weather cooling of renal parenchyma by several irrigation
      solutions which have different electric conductivity (EC) such as normal saline
      solution (EC: 15,800 microS/cm), tap water (EC: 133 microS/cm) and glucose
      solution (EC: 8.6 microS/cm) in the renal pelvis using ureteral catheter would
      effect on the distribution of temperature and the area of tissue degeneration. In
      MCT and USS, these solutions did not have any effect, but in RFA the degree of
      tissue temperature elevation by normal saline, tap water and glucose solution
      were high, intermediate and low, respectively. CONCLUSION: As RFA and USS tend to
      be affected by the surrounding environment, electric and thermal conductivity
      should be applied with caution, while using these techniques.

PMID- 18062212
TI  - [Carcinoma of penis: report of 59 cases and review of literature].
AB  - PURPOSE: To analyze the characteristics and prognostic factor of penile cancer,
      we retrospectively reviewed the clinicopathological data of patients with a
      diagnosis of penile cancer treated. PATIENTS AND METHODS: The records of 59
      patients (median age 66, ranged from 47 to 91) with squamous cell carcinoma of
      the penis reffered between April 1988 and January 2006 were reviewed. The
      importance of tumor size and stage, differentiation, type of infiltration,
      vascular invasion, patient age, lymph node metastasis, distant metastasis and
      type of therapy were assessed using univariate and multivariate analyses.
      RESULTS: After a mean follow up of 37.7 months, 13 cases (22.0%) died of cancer
      and 5-year survival was 67.4%. Multivariate analysis demonstrated that, type of
      operation (p = 0.0471, Hazard ratio 3.364), vascular invasion (p = 0.0014, Hazard
      ratio 5.921) were associated with survival. CONCLUSION: Vascular invasion and
      type of operation were related to survival. Our findings indicate that correct
      pathological diagnosis and appropriate treatment may lead to prolonged survival.

PMID- 18062213
TI  - [Vesicosigmoidal fistula caused by diverculitis: report of cases and literature
      review in Japan].
AB  - BACKGROUND: In Japan, patients suffering vesicosigmoidal fistula caused by
      diverculitis is increasing. Our aim is to report our seven cases and the
      literature review related with this disease. METHODS: A retrospective record
      review of seven patients in our hospital who were diagnosed and treated for
      vesicosigmoidal fistulas over a 12-year period from 1994 was performed. Data
      collection focused on symptoms, diagnostic studies, and methods of management.
      RESULTS: All of the patients were male whose ages ranged from 41 to 82 years,
      with a mean age of 60.7 years. All of the patients presented with some of the
      common presenting symptoms of pneumaturia, fecaluria, irritation, abdominal pain,
      recurrent urinary tract infection, macroscopic hematuria. In all cases, abnormal
      cystoscopic findings were observed. Onestage colectomy with partial cystectomy
      was underwent in all cases. CONCLUSION: Many of the patients suffering from
      vesicosigmoidal fistula caused by diverticulitis have urological symptoms. So the
      above mentioned examinations are required when the outpatients complained of
      pneumaturia, fecaluria, irritative voiding symptoms, reccurent urinary tract
      infection. After diagnosed, surgical treatment is the most standard therapy and
      when the appropriate operative method is selected, postoperative prognosis is
      favorable.

PMID- 18062214
TI  - [Angiomyolipoma in the renal pelvis].
AB  - A 54-year-old male presented with massive hematuria with bladder tamponade.
      Computed tomography and magnetic resonance imaging showed a 7.5 x 6.5 x 4.5 cm.
      mass centered in the left renal pelvis, which is composed of macroscopic fat and
      soft-tissue component. Differential diagnosis included liposarcoma, lipoma and
      angiomyolipoma. Urothelial carcinoma was also undeniable because urine cytology
      was equivocal. Subsequently, a left nephroureterectomy was performed.
      Pathological examinations revealed a renal angiomyolipoma protruding into the
      renal pelvis. We present a rare case of angiomyolipoma in the renal pelvis and
      review the literature concerning these unusual findings of this common neoplasm.

PMID- 18062215
TI  - [Spontaneous migration of a metal clip into renal pelvis after laparoscopic
      pyeloplasty: a case report].
AB  - Migration of surgical materials into the urinary tract is very rare. We present a
      case of spontaneous migration of a metal clip into renal pelvis after
      laparoscopic pyeloplasty. A 44-year-old woman who had a long history of multiple
      sclerosis presented with symptomatic left hydronephrosis due to ureteropelvic
      junction (UPJ) obstruction. Since antegrade endopyelotomy was unsuccessful, the
      patient underwent laparoscopic Anderson-Hynes pyeloplasty. The UPJ was wrapped
      with thick inflammatory tissue and a crossing vessel that firmly adhered to the
      UPJ was found and dissected. Metal clips were used for hemostasis. Although the
      hydronephrosis was improved and flank pain was completely dissolved, a stone was
      identified in the pelvis 22 months after the surgery. The stone was formed around
      a metal clip that had been possibly migrated into the renal pelvis. Transureteral
      lithotripsy was performed using an 8F ureterofiberscope and a clip was removed.

PMID- 18062216
TI  - [Renal parencymal malacoplakia successfully treated with conservative therapy; a
      case report].
AB  - Malacoplakia is a relatively rare form of chronic granulomatous inflammation.
      Which occurs most frequently in the genito-urinary system, but renal parenchymal
      involvement is rare. We present a case of malacoplakia of the renal parenchyma. A
      69-year-old woman with left renal mass was referred to our department. Abdominal
      enhanced CT scan revealed heterogeneous mass in the left kidney (50 x 45 mm). CT
      guided percutaneous left renal needle biopsy confirmed the diagnosis of renal
      malakoplakia. We successfully treated her with oral levofloxacin. The lesion
      resolved after the 4-months-therapy, and there has been no recurrence for 22
      months since the treatment.

PMID- 18062217
TI  - [Bilateral pheochromocytomas with von Hippel-Lindau disease: a case report].
AB  - A case of bilateral pheochromocytomas with von Hippel Lindau disease (VHL) is
      reported. A 32-year-old man visited Kumamoto Red Cross Hospital for further
      examination of hypertension. Computed tomography revealed bilateral adrenal
      tumors and noradrenalin levels in serum and urine were elevated. Suspecting
      bilateral pheochromocytoma, he was reffered to our hospital for further
      examination and treatment. 131I-MIBG scintigraphy showed accumulation in
      bilateral adrenal glands. Moreover, he had cerebellar and spinal
      hemangioblastomas. Bilateral adrenalectomies and left nephrectomy were performed
      because tumor thrombus extended into the left renal vein, and pathological
      diagnosis was pheochromocytoma. His sister had been diagnosed as VHL disease. We
      diagnosed the patient as VHL disease because of the existence of cerebellar and
      spinal hemangioblastomas, bilateral pheochromocytomas, missense mutation and his
      family history. This is the eleventh case of bilateral pheochromocytomas with VHL
      disease reported in Japanese literatures.

PMID- 18062218
TI  - Burkholderia diversity and versatility: an inventory of the extracellular
      products.
AB  - The Burkholderia genus consists of over 40 Gram-negative, beta-proteobacteria
      species that occupy remarkably diverse ecological niches. This genus contains
      species pathogenic to human, animals, and plants, as well as species involved in
      promoting plant growth and biodegradation of pollutants. This is largely
      explained by the extraordinary versatility of Burkholderia, as reflected by the
      remarkable diversity of extracellular products released by these bacteria. We
      exhaustively surveyed the extracellular enzymes, siderophores, toxins,
      antimicrobials, and other secondary metabolites produced by the members of this
      very diverse genus. Available information on regulation, especially quorum
      sensing mechanisms, and secretion is highlighted.

PMID- 18062219
TI  - Degradation of raffinose oligosaccharides in soymilk by immobilized alpha
      galactosidase of Aspergillus oryzae.
AB  - Alpha-galactosidase was immobilized in a mixture of k-carrageenan and locust bean
      gum. The properties of the free and immobilized enzyme were then determined. The
      optimum pH for both the soluble and immobilized enzyme was 4.8. The optimum
      temperature for the soluble enzymes was 50 degrees C, whereas that for the
      immobilized enzyme was 55 degrees C. The immobilized enzyme was used in batch,
      repeated batch, and continuous modes to degrade the raffinose-family sugars
      present in soymilk. Two hours of incubation with the free and immobilized alpha
      galactosidases resulted in an 80% and 68% reduction in the raffinose
      oligosaccharides in the soymilk, respectively. In the repeated batch, a 73%
      reduction was obtained in the fourth cycle. A fluidized bed reactor was also
      designed to treat soymilk continuously and the performance of the immobilized
      alpha-galactosidase tested at different flow rates, resulting in a 90% reduction
      of raffinose-family oligosaccharides in the soymilk at a flow rate 40 ml/h.
      Therefore, the present study demonstrated that immobilized alpha-galactosidase in
      a continuous mode is efficient for reducing the oligosaccharides present in
      soymilk, which may be of considerable interest for industrial application.

PMID- 18062220
TI  - Development of predictive mathematical model for the growth kinetics of
      Staphylococcus aureus by response surface model.
AB  - A response surface model was developed for predicting the growth rates of
      Staphylococcus aureus in tryptic soy broth (TSB) medium as a function of combined
      effects of temperature, pH, and NaCl. The TSB containing six different
      concentrations of NaCl (0, 2, 4, 6, 8, and 10%) was adjusted to an initial of six
      different pH levels (pH 4, 5, 6, 7, 8, 9, and 10) and incubated at 10, 20, 30,
      and 40 degrees C. In all experimental variables, the primary growth curves were
      well (r2=0.9000 to 0.9975) fitted to a Gompertz equation to obtain growth rates.
      The secondary response surface model for natural logarithm transformations of
      growth rates as a function of combined effects of temperature, pH, and NaCl was
      obtained by SAS's general linear analysis. The predicted growth rates of the S.
      aureus were generally decreased by basic (pH 9-10) or acidic (pH 5-6) conditions
      and higher NaCl concentrations. The response surface model was identified as an
      appropriate secondary model for growth rates on the basis of correlation
      coefficient (r=0.9703), determination coefficient (r2=0.9415), mean square error
      (MSE=0.0185), bias factor (B(f)=1.0216), and accuracy factor (A(f)=1.2583).
      Therefore, the developed secondary model proved reliable for predictions of the
      combined effect of temperature, NaCl, and pH on growth rates for S. aureus in TSB
      medium.

PMID- 18062221
TI  - Flatfish vitellogenin detection using optical waveguide lightmode spectroscopy
      based immunosensor.
AB  - A sensitive optical waveguide lightmode spectroscopy-based immunosensor was
      developed to detect vitellogenin in seawater flatfish (Paralichthys olivaceus).
      For this purpose, anion-exchange column chromatography with DE-52 resin was used
      to purify flatfish vitellogenin from flatfish serum containing vitellogenin that
      had been induced using an intraperitoneal 17beta-estradiol injection. The anti
      flatfish vitellogenin antibody used as the biological component of the above
      immunosensor was prepared using the purified flatfish vitellogenin. The change in
      the incoupling angle according to the complexation between the flatfish
      vitellogenin and its antibody, immobilized over an optical grating coupler sensor
      chip, was measured to calculate the sensor response. The immunosensor was quite
      specific to flatfish vitellogenin binding, based on no sensor response in the
      case of bovine serum albumin immobilization. When plotted using double
      logarithmic scales, the sensor responses increased linearly in flatfish
      vitellogenin concentrations of 0.00675-67.5 nM, with a detection limit of 0.0675
      nM. The reusability during seven repetitive measurements was reasonably fair for
      the preliminary screening of flatfish vitellogenin.

PMID- 18062222
TI  - Requirement of Fur for the full induction of Dps expression in Salmonella
      enterica serovar typhimurium.
AB  - The Dps protein, which is overexpressed in harsh environments, is known to play a
      critical role in the protection of DNA against oxidative stresses. In this study,
      the roles of Fur in the expression of the dps gene in Salmonella and the
      protection mechanisms against oxidative stress in Salmonella cells preexposed to
      iron-stress were investigated. Two putative Fur boxes were predicted within the
      promoter region o f th e S. typhimurium dps gene . The profile of dps expression
      performed by the LacZ reporter assay revealed growth-phase dependency regardless
      of iron-status under the culture conditions. Thefur mutant, chi4659, evidenced a
      reduced level of beta-galactosidase as compared to the wild-type strain. The
      results observed after the measurement of the Dps protein in various Salmonella
      regulatory mutants were consistent with the results acquired in the reporter
      assay. This evidence suggested that Fur performs a function as a subsidiary
      regulator in the expression of dps. The survival ability of Salmonella strains
      after exposure to oxidative stress demonstrated that the Dps protein performs a
      pivotal function in the survival of stationary-phase S. typhimurium against
      oxidative stress. Salmonella cells grown in iron-restricted condition required
      Dps for full protection against oxidative stress. The CK24 (Deltadps) cells grown
      in iron-replete condition survived at a rate similar to that observed in the wild
      type strain, thereby suggesting the induction of an unknown protection
      mechanism(s) other than Dps in this condition.

PMID- 18062223
TI  - Cloning and characterization of monofunctional catalase from photosynthetic
      bacterium Rhodospirillum rubrum S1.
AB  - In this study, an approx. 2.5-kb gene fragment including the catalase gene from
      Rhodospirillum rubrum S1 was cloned and characterized. The determination of the
      complete nucleotide sequence revealed that the cloned DNA fragment was organized
      into three open reading frames, designated as ORF1, catalase, and ORF3 in that
      order. The catalase gene consisted of 1,455 nucleotides and 484 amino acids,
      including the initiation and stop codons, and was located 326 bp upstream in the
      opposite direction of ORF1. The catalase was overproduced in Escherichia coli
      UM255, a catalase-deficient mutant, and then purified for the biochemical
      characterization of the enzyme. The purified catalase had an estimated molecular
      mass of 189 kDa, consisting of four identical subunits of 61 kDa. The enzyme
      exhibited activity over a broad pH range from pH 5.0 to pH 11.0 and temperature
      range from 20 degrees C to 60 degrees C. The catalase activity was inhibited by 3
      amino-1,2,4-triazole, cyanide, azide, and hydroxylamine. The enzyme's K(m) value
      and V(max) of the catalase for H2O2 were 21.8 mM and 39,960 U/mg, respectively.
      Spectrophotometric analysis revealed that the ratio of A406 to A280 for the
      catalase was 0.97, indicating the presence of a ferric component. The absorption
      spectrum of catalase-4 exhibited a Soret band at 406 nm, which is typical of a
      heme-containing catalase. Treatment of the enzyme with dithionite did not alter
      the spectral shape and revealed no peroxidase activity. The combined results of
      the gene sequence and biochemical characterization proved that the catalase
      cloned from strain S1in this study was a typical monofunctional catalase, which
      differed from the other types of catalases found in strain S1.

PMID- 18062224
TI  - Purification and characterization of a new fibrinolytic enzyme of Bacillus
      licheniformis KJ-31, isolated from Korean traditional Jeot-gal.
AB  - Jeot-gal is a traditional Korean fermented seafood and has long been used for
      seasoning. We isolated 188 strains from shrimp, anchovy, and yellow corvina Jeot
      gal, and screened sixteen strains that showed strong fibrinolytic activities on a
      fibrin plate. Among those strains, the strain that had the largest halo zone was
      chosen and identified as Bacillus licheniformis by using 16S rDNA sequencing and
      an API CHB kit. The fibrinolytic activity of Bacillus licheniformis was
      characterized and designated as bpKJ-31. The active component of bpKJ-31 was
      identified as a 37 kDa protein, designated bacillopeptidase F, by internal
      peptide mapping and N-terminal sequencing. The optimum activity of bpKJ-31 was
      shown at pH 9 and 40 degrees C, with a chromogenic substrate for plasmin. It had
      high degrading activity for the Bbeta-chain and Aalpha-chain of fibrin(ogen), and
      also acted on thrombin, but not skim milk and casein. The amidolytic activity of
      bpKJ-31 was inhibited by 1 mM phenylmethanesulfonyl fluoride, but 1 mM EDTA did
      not affect the enzyme activity, indicating that bpKJ-31 is an alkaline serine
      protease, like a plasmin. The bpKJ-31 showed approximately 14.3% higher
      fibrinolytic activity than the plasmin. These features of bpKJ-31 make it
      attractive as a health-promoting biomaterial.

PMID- 18062225
TI  - Zinc metal solubilization by Gluconacetobacter diazotrophicus and induction of
      pleomorphic cells.
AB  - Gluconacetobacter diazotrophicus strain PAl5 exhibited a minimum inhibitory
      concentration value of 11 mM in an LGI medium amended with ZnCl2. When an LGI
      medium was amended with Zn metal, solubilization halos were observed in a plate
      assay, and further solubilization was confirmed in a broth assay. The maximum
      solubilization was recorded after 120 h with a 0.1% Zn metal amendment. During
      solubilization, the culture growth and pH of the broth were indirectly
      correlated. Using a Fourier Transform Infrared Spectroscopy analysis, one of the
      agents solubilizing the Zn metal was identified as gluconic acid. When the Zn
      amended broth was observed under a bright field microscope, long involution cells
      were observed, and further analysis with Atomic Force Microscopy revealed highly
      deformed, pleomorphic, aggregate-like cells.

PMID- 18062226
TI  - Granulosicoccaceae fam. nov., to include Granulosicoccus antarcticus gen. nov.,
      sp. nov., a non-phototrophic, obligately aerobic chemoheterotroph in the order
      Chromatiales, isolated from Antarctic seawater.
AB  - A Gram-negative, motile by tuft flagella, obligately aerobic
      chemoorganoheterotrophic, sphere-form bacterium, designated IMCC3135(T), was
      isolated from the Antarctic surface seawater of King George Island, West
      Antarctica. The strain was mesophilic, neutrophilic, and requiring NaCl for
      growth, but neither halophilic nor halotolerant. The 16S rRNA gene sequence
      analysis indicated that the strain was most closely related to genera of the
      order Chromatiales in the class Gammaproteobacteria. The most closely related
      genera showed less than 90% 16S rRNA gene sequence similarity and included
      Thioalkalispira (89.9%), Thioalkalivibrio (88.0%-89.5%), Ectothiorhodospira
      (87.9%-89.3%), Chromatium (88.3%-88.9%), and Lamprocystis (87.7%-88.9%), which
      represent three different families of the order Chromatiales. Phylogenetic
      analyses showed that this Antarctic strain represented a distinct phylogenetic
      lineage in the order Chromatiales and could not be assigned to any of the defined
      families in the order. Phenotypic characteristics, including primarily non
      phototrophic, non-alkaliphilic, non-halophilic, and obligately aerobic
      chemoheterotrophic properties, differentiated the strain from other related
      genera. The very low sequence similarities (<90%) and distant relationships
      between the strain and members of the order suggested that the strain merited
      classification as a novel genus within a novel family in the order Chromatiales.
      On the basis of these taxonomic traits, a novel genus and species is proposed,
      Granulosicoccus antarcticus gen. nov., sp. nov., in a new family
      Granulosicoccaceae fam. nov. Strain IMCC3135(T) (=KCCM 42676(T)=NBRC 102684(T))
      is the type strain of Granulosicoccus antarcticus.

PMID- 18062227
TI  - Anti-inflammatory effects of recombinant arginine deiminase originating from
      Lactococcus lactis ssp. lactis ATCC 7962.
AB  - Arginine deiminase (ADI, E.C. 3.5.3.6), one of the arginine deprivation enzymes,
      exhibits anticarcinogenic activities. The present study investigated the anti
      inflammatory activities of the purified recombinant ADI originating from
      Lactococcus lactis ssp. lactis ATCC7962 (LADI). LADI dose-dependently inhibited
      lipopolysaccharide (LPS)-induced upregulation of inducible nitric oxide synthase
      and the production of nitric oxide in RAW 264.7 murine macrophages. The induction
      of cyclooxygenase-2 expression and subsequent production of prostaglandin E2 by
      LPS was also attenuated by LADI treatment. Moreover, LADI inhibited the
      production of interleukin-6 in LPS-stimulated RAW 264.7 macrophages. These
      results indicate that LADI exerts anti-inflammatory effects, which may in part
      explain its chemopreventive potential.

PMID- 18062228
TI  - Isolation and characterization of strain of Bacillus thuringiensis subsp. kenyae
      containing two novel cry1-type toxin genes.
AB  - To identify novel crystal proteins, Bacillus thuringiensis 2385-1 was isolated
      from Korean soil samples and characterized. The H-serotype of 2385-1 was
      identical to that of subsp. kenyae (H4a4c), and its crystal toxin was bipyramidal
      shaped. However, 2385-1 showed a much higher toxicity towards Plutella xylostella
      and Spodoptera exigua larvae than subsp. kenyae. In addition, the crystal protein
      profile and plasmid DNA pattern of 2385-1 differed from those of subsp. kenyae.
      To verify the crystal protein gene types of 2385-1, a PCR-RFLP analysis was
      performed, and the results revealed that 2385-1 contained two novel cry1-type
      crystal protein genes, cry1-5 and cry1-12, in addition to the cry1Ja1 gene. The
      deduced amino acid sequences of cry1-5 and cry1-12 showed a 97.9% and 75.7%
      sequence similarity with the CrylAb and Cry1Ja crystal proteins, respectively.
      Among the novel crystal proteins, Cry1-5 showed a high toxicity towards P.
      xylostella and S. exigua larvae. In conclusion, B. thuringiensis 2385-1 is a new
      isolate in terms of its gene types, and should be a promising source for an
      insecticide to control lepidopteran larvae.

PMID- 18062229
TI  - Molecular characterization of fprB (ferredoxin-NADP+ reductase) in Pseudomonas
      putida KT2440.
AB  - The fpr gene, which encodes a ferredoxin-NADP+ reductase, is known to participate
      in the reversible redox reactions between NADP+/NADPH and electron carriers, such
      as ferredoxin or flavodoxin. The role of Fpr and its regulatory protein, FinR, in
      Pseudomonas putida KT2440 on the oxidative and osmotic stress responses has
      already been characterized [Lee at al. (2006). Biochem. Biophys. Res. Commun.
      339, 1246-1254]. In the genome of P. putida KT2440, another Fpr homolog (FprB)
      has a 35.3% amino acid identity with Fpr. The fprB gene was cloned and expressed
      in Escherichia coli. The diaphorase activity assay was conducted using purified
      FprB to identify the function of FprB. In contrast to the fpr gene, the induction
      of fprB was not affected by oxidative stress agents, such as paraquat, menadione,
      H2O2 and t-butyl hydroperoxide. However, a higher level of fprB induction was
      observed under osmotic stress. Targeted disruption of fprB by homologous
      recombination resulted in a growth defect under high osmotic conditions. Recovery
      of oxidatively damaged aconitase activity was faster for the fprB mutant than for
      the fpr mutant, yet still slower than that for the wild type. Therefore, these
      data suggest that the catalytic function of FprB may have evolved to augment the
      function of Fpr in P. putida KT2440.

PMID- 18062230
TI  - Antitumor effect of soluble beta-1,3-glucan from Agrobacterium sp. R259 KCTC
      1019.
AB  - Beta-1,3-glucans enhance immune reactions such as antitumor, antibacterial,
      antiviral, anticoagulatory, and wound healing activities. beta-1,3-Glucans have
      various functions depending on the molecular weight, degree of branching,
      conformation, water solubility, and intermolecular association. The molecular
      weight of the soluble glucan was about 15,000 as determined by a high-performance
      size exclusion chromatography. From the infrared (IR) and 13C NMR analytical
      data, the purified soluble glucan was found to exclusively consist of beta-D
      glucopyranose with 1,3 linkage. We tested the immunestimulating activities of the
      soluble beta-1,3-glucan extracted from Agrobacterium sp. R259 KCTC 1019 and
      confirmed the following activities. IFN-gamma and each cytokines were induced in
      the spleens and thymus of mice treated with soluble beta-1,3-glucan. Adjuvant
      effect was observed on antibody production. Nitric oxide was synthesized in
      monocytic cell lines treated with beta-1,3-glucan. The cytotoxic and antitumor
      effects were observed on various cancer cell lines and ICR mice. These results
      strongly suggested that this soluble beta-1,3-glucan could be a good candidate
      for an immune-modulating agent.

PMID- 18062231
TI  - Extracellular secretion of a maltogenic amylase from Lactobacillus gasseri
      ATCC33323 in Lactococcus lactis MG1363 and its application on the production of
      branched maltooligosaccharides.
AB  - A maltogenic amylase gene from Lactobacillus gasseri ATCC33323 (LGMA) was
      expressed in Lactococcus lactis MG1363 using the P170 expression system. The
      successful production of recombinant LGMA (rLGMA) was confirmed by the catalytic
      activity of the enzyme in liquid and solid media. The N-terminal amino acid
      sequencing analysis of the rLGMA showed that it was Met-Gln-Leu-Ala-Ala-Leu-,
      which was the same as that of genuine protein, meaning the signal peptide was
      efficiently cleaved during secretion to the extracellular milieu. The optimal
      reaction temperature and pH of rLGMA (55 degrees C and pH 5, respectively) and
      enzymatic hydrolysis patterns on various substrates (beta-cyclodextrin, starch,
      and pullulan) supported that rLGMA was not only efficiently secreted from the
      Lactococcus lactis MG1363 but was also functionally active. Finally, the branched
      maltooligosaccharides were effectively produced from liquefied corn starch, by
      using rLGMA secreted from Lactococcus lactis, with a yield of 53.1%.

PMID- 18062232
TI  - Effects of ionic speciation of lysine on its adsorption and desorption through a
      sulfone-type ion-exchange column.
AB  - Lysine produced during microbial fermentation is usually recovered by an ion
      exchange process, in which lysine is first converted to the cationic form (by
      lowering the pH to less than 2.0 with sulfuric acid) and then fed to a cation
      exchange column containing an exchanger that has a sulfone group with a weak
      counterion such as NH4+. Ammonia water with a pH above 11 is then supplied to the
      column to displace the purified lysine from the column and allow its recovery. To
      enhance the adsorption capacity and for a possible reduction in chemical
      consumption, monovalent lysine fed at pH 4 was investigated in comparison with
      conventional divalent lysine fed at pH 1.5. The adsorption capacity increased by
      more than 70% on a mass basis using pH 4 feeding compared with pH 1.5 feeding.
      Lysine adsorbed at pH 4 started to elute earlier than that adsorbed at pH 1.5
      when ammonia water was used as the eluant solution, and the extent of early
      elution became more notable at lower concentrations of ammonia. Moreover, the
      elution of monovalent lysine fed at pH 4 displayed a stiffer front boundary and
      higher peak concentration. However, when the ammonium concentration was greater
      than 2.0 N, complete saturation of the bed was delayed during adsorption and the
      percent recovery yield from elution was lowered, both drawbacks that were
      considered inevitable features originating from the increased adsorption of
      monovalent lysine.

PMID- 18062233
TI  - Continuous production of lactosucrose by immobilized Sterigmatomyces elviae
      mutant.
AB  - In this study, in order to develop a continuous production process of
      lactosucrose in a packed-bed reactor, Sterigmatomyces elviae ATCC 18894 was
      selected and mutated. The mutant strain of S. elviae showed 54.3% higher
      lactosucrose production than the wild type. Reaction conditions such as
      temperature, pH, substrate concentration and flow rate were also optimized. Under
      optimized reaction conditions (50 degrees C, pH 6.0, 25% sucrose and 25% lactose
      as substrate, flow rate 1.2 ml/min), the maximum concentration of lactosucrose
      (192 g/l) was obtained. In a packed-bed reactor, continuous production of
      lactosucrose was performed using S. elviae mutant immobilized in calcium
      alginate, and about 180 g/l of lactosucrose production was achieved for 48 days.

PMID- 18062234
TI  - Enhancement of clavulanic acid by replicative and integrative expression of ccaR
      and cas2 in Streptomyces clavuligerus NRRL3585.
AB  - Clavulanic acid (CA) is an inhibitor of beta-lactamase that is produced from
      Streptomyces clavuligerus NRRL3585 and is used in combination with other
      antibiotics in clinical treatments. In order to increase the production of CA,
      the replicative and integrative expressions of ccaR (encoding for a specific
      regulator of the CA biosynthetic operon) and cas2 (encoding for the rate-limiting
      enzyme in the CA biosynthetic pathway) were applied. Six recombinant plasmids
      were designed for this study. The pIBRHL1, pIBRHL3, and pIBRHL13 were constructed
      for overexpression, whereas pNQ3, pNQ2, and pNQ1 were constructed for chromosomal
      integration with ccaR, cas2, and ccaR-cas2, respectively. All of these plasmids
      were transformed into S. clavuligerus NRRL3585. CA production in transformants
      resulted in a significantly enhanced amount greater than that of the wild type, a
      2.25-fold increase with pIBRHL1, a 9.28-fold increase with pNQ3, a 5.06-fold
      increase with pIBRHL3, a 2.93-fold increase with pNQ2 integration, a 5.79-fold
      increase with pIBRHL13, and a 23.8-fold increase with pNQ1. The integrative pNQ1
      strain has been successfully applied to enhance production.

PMID- 18062235
TI  - Chemopreventive effect of chitosan oligosaccharide against colon carcinogenesis.
AB  - Chitosan oligosaccharide (COS, 3 kDa<MW<5 kDa) was tested for colon cancer
      chemoprevention by measuring the activities of quinine reductase (QR) and
      glutathione-S-transferase (GST), glutathione (GSH) levels, ornithine
      decarboxylase (ODC) activity, and cyclooxygenase (COX)-2 expression in HT-29
      cells treated with COS. COS induced QR activity in a dose-dependent manner over a
      concentration range of 0.1-4.0 mg/ml. GST activity was also induced in HT-29
      cells treated with COS. In addition, GSH levels were increased 1.3-, 1.4-, and
      1.5-fold with COS at 2, 3, and 4 mg/ml, respectively. ODC activity induced by 12
      O-tetradecanoylphorbol-13-acetate (TPA) was inhibited by 33% and 39% with 3 and 4
      mg/ml of COS, respectively. COS also inhibited the expression of TPA-induced COX
      2 protein in HT-29 cells. These results suggest that COS has colon cancer
      chemopreventive activity by increasing QR and GST activities and GSH levels and
      by inhibiting ODC activity and COX-2 expression in vitro.

PMID- 18062236
TI  - Functional characteristics of cyclodextrin glucanotransferase from alkalophilic
      Bacillus sp. BL-31 highly specific for intermolecular transglycosylation of
      bioflavonoids.
AB  - The functional characteristics of a beta-cyclodextrin glucanotransferase (CGTase)
      excreted from alkalophilic Bacillus sp. BL-31 that is highly specific for the
      intermolecular transglycosylation of bioflavonoids were investigated. The new
      beta-CGTase showed high specificities for glycosyl acceptor bioflavonoids,
      including naringin, rutin, and hesperidin, and especially naringin. The
      transglycosylation of naringin into glycosyl naringin was then carried out under
      the conditions of 80 units of CGTase per gram of maltodextrin, 5 g/l of naringin,
      25 g/l of maltodextrin, and 1 mM Mn2+ ion at 40 degrees C for 6 h, resulting in a
      high conversion yield of 92.1%.

PMID- 18062237
TI  - Antiasthmic effect of fermented Artemisia princeps in asthmic mice induced by
      ovalbumin.
AB  - Artemisia princeps Pampanini (AP) was fermented with Bifidobacterium infantis K
      525 and its antiasthmic effect investigated. AP and fermented AP (FAP) reduced
      the IgE level in the blood of ovalbumin-induced asthmic mice. Moreover, FAP
      reduced the IgE, proinflammatory cytokine IL-6, and IL-4 levels in the trachea,
      as well as in the lung of the experimental asthmic mice, whereas AP only reduced
      the IgE and IL-6 levels in the lungs. Nonetheless, AP and FAP both inhibited the
      mRNA expression of IL-6 and TNF-alpha in IgE-induced RBL-2H3 cells. The in vivo
      antiasthmic effect of FAP was more potent than that of AP. Therefore, these
      findings suggest that the enhanced antiasthmic effect of AP after bifidus
      fermentation was possibly due to the regulation of the proinflammatory cytokine
      biosynthesis of IL-6 and TNF-alpha.

PMID- 18062238
TI  - Influence of pipe materials and VBNC cells on culturable bacteria in a
      chlorinated drinking water model system.
AB  - To elucidate the influence of pipe materials on the VBNC (viable but
      nonculturable) state and bacterial numbers in drinking water, biofilm and
      effluent from stainless steel, galvanized iron, and polyvinyl chloride pipe
      wafers were analyzed. Although no HPC (heterotrophic plate count) was detected in
      the chlorinated influent of the model system, a DVC (direct viable count) still
      existed in the range between 3- and 4-log cells/ml. Significantly high numbers of
      HPC and DVC were found both in biofilm and in the effluent of the model system.
      The pipe material, exposure time, and the season were all relevant to the
      concentrations of VBNC and HPC bacteria detected. These findings indicate the
      importance of determining the number of VBNC cells and the type of pipe materials
      to estimate the HPC concentration in water distribution systems and thus the need
      of determining a DVC in evaluating disinfection efficiency.

PMID- 18062239
TI  - Two threonine residues required for role of AfsKav in controlling morphogenesis
      and avermectin production in Streptomyces avermitilis.
AB  - AfsKav is a eukaryotic-type serine/threonine protein kinase, required for
      sporulation and avermectin production in Streptomyces avermitilis. In terms of
      their ability to complement SJW4001 (DeltaafsK-av), afsK-av mutants T165A and
      T168A were not functional, whereas mutants T165D and T168D retained their
      ability, indicating that Thr-165 and Thr-168 are the phosphorylation sites
      required for the role of AfsKav. Expression of the S-adenosylmethione synthetase
      gene promoted avermectin production in the wild-type S. avermitilis, yet not in
      the mutant harboring T168D or T165D, demonstrating that tandem phosphorylation on
      Thr-165 and Thr-168 in AfsKav is the mechanism modulating avermectin production
      in response to S-adenosylmethione accumulation in S. avermitilis.

PMID- 18062240
TI  - Fumigant activity of essential oils and components of Illicium verum and
      Schizonepeta tenuifolia against Botrytis cinerea and Colletotrichum
      gloeosporioides.
AB  - To develop a natural fungicide against Botrytis cinerea and Colletotrichum
      gloeosporioides, a total of 25 essential oils were tested for their fumigant
      activity against post-harvest pathogens. The vaporous phases of oils were treated
      to each fungus on potato dextrose agar medium in half-plate separated Petri
      plates at 10 microg per plate. The essential oil of Illicium verum strongly
      inhibited the mycelial growth of both B. cinerea and C. gloeosporioides by over
      90%. On the other hand, the essential oil of Schizonepeta tenuifolia showed
      inhibitory activity against mycelial growth of only B. cinerea by over 90%. Gas
      chromatography-mass spectrometry and bioassay indicated trans-anethole in I.
      verum and menthone in S. tenuifolia as a major antifungal constituent. The
      essential oils of I. verum and S. tenuifolia and their major constituents could
      be used to manage post-harvest diseases caused by B. cinerea and C.
      gloeosporioides.

PMID- 18062241
TI  - Cytotoxic effects of nanoparticles assessed in vitro and in vivo.
AB  - An increasing number of applications is being developed for the use of
      nanoparticles in various fields. We investigated possible toxicities of
      nanoparticles in cell culture and in mice. Nanoparticles tested were Zn (300 nm),
      Fe (100 nm), and Si (10-20, 40-50, and 90-110 nm). The cell lines used were
      brain, liver, stomach, and lung from humans. In the presence of nanopaticles,
      mitochodrial activity decreased zero to 15%. DNA contents decreased zero to 20%,
      and glutathione production increased zero to 15%. None of them showed a dose
      dependency. Plasma membrane permeability was not altered by nanoparticles. In the
      case of Si, different sizes of the nanoparticles did not affect cytotoxicity. The
      cytotoxicity was also shown to be similar in the presence of micro-sized (45
      microm) Si particles. Organs from mice fed with nanoparticles showed nonspecific
      hemorrhage, lymphocytic infiltration, and medullary congestion. A treatment with
      the micro-sized particle showed similar results, suggesting that the acute in
      vivo toxicity was not altered by nano-sized particles.

PMID- 18062242
TI  - 5-aminolevulinic acid biosynthesis in Escherichia coli coexpressing NADP
      dependent malic enzyme and 5-aminolevulinate synthase.
AB  - 5-aminolevulinate (ALA) synthase (E.C. 2.3.1.37), which mediates the pyridoxal
      phosphate-dependent condensation of glycine and succinyl-CoA, encoded by the
      Rhodobacter sphaeroides hemA gene, enables Escherichia coli strains to produce
      ALA at a low level. To study the effect of the enhanced C4 metabolism of E. coli
      on ALA biosynthesis, NADP-dependent malic enzyme (maeB, E.C. 1.1.1.40) was
      coexpressed with ALA synthase in E. coli. The concentration of ALA was two times
      greater in cells coexpressing maeB and hemA than in cells expressing hemA alone
      under anaerobic conditions with medium containing glucose and glycine. Enhanced
      ALA synthase activity via coupled expression of hemA and maeB may lead to
      metabolic engineering of E. coli capable of large-scale ALA production.

PMID- 18062243
TI  - [Soil microbial diversity of artificial peashrub plantation on North Loess
      Plateau of China].
AB  - Peashrub (Caragana korshinskii Kom) is a kind of excellent shrub used for dune
      fixation in Loess Plateau of China. In order to explore relationship between
      peashrub and soil microorganisms, microbial communities diversity associated with
      rhizoplane, rhizosphere and bulk soil of peashrub in Loess Plateau of China were
      characterized based on a culture-independent approach. Three 16S rDNA gene
      libraries were constructed, respectively, and each different profile was used to
      define an operational taxonomic unit (OTU). The numbers of microorganisms
      decreased as root proximity decreased and a few OTUs became dominant.
      Phylogenetic analyses indicated that Proteobacteria was the predominant group in
      rhizoplane, which included many alpha-Proteobacteria, partially consisted of
      rhizobia, and gamma-Proteobacteria beneficial to plant growth. In bulk soil, the
      most frequent OTUs were closely related to Archaea, while Acidobacteria was the
      dominant group in rhizosphere of peashrub. The diversity index (H') was higher in
      rhizosphere than in rhizoplane and bulk soil, whereas microbial populations in
      rhizoplane and bulk soil had the greater dominance indices (D). It was shown that
      there was a significant change in microbial species composition along the root
      gradient, shifting from complex plant-associated bacterial community in the root
      habitats to a simple bacterial community in the bulk soil. These results showed
      that plant roots and soil conditions created a selective environment for
      microbial populations.

PMID- 18062244
TI  - [Micirobial diversity and screening of antitumor activity of actinomycete strains
      from saline and alkaline environments in the Qinghai Province, P. R. China].
AB  - Soil and sediment samples were collected from saline and alkaline soils or lakes
      in the Qinghai Province, northwestern China. 145 actinomycete strains were
      isolated using Glucose-Peptone-Yeast extract agar (GPY) and ISP medium 2 agar
      supplemented with 1.0 - 3.0 mol/L NaCl at pH 7.5 - 10. The antitumor activities
      in vitro of the fermentation broth extracts from the 145 test strains were
      detected in 6 human tumor cell lines (gastric cancer GXF251L, lung cancer
      LXFL529L, mammary cancer MAXF401NL, melanoma cancer MEXF462NL, renal cancer
      RXF486L and uterus cancer UXF1138L). Out of 145 test strains, 26 strains were
      positive in antitumor activities (17.9%), among them 19 strains belong to the
      genus Nocardiopsis, 7 strains belong to the genus Streptomyces. Then 8 antitumor
      positive strains were submitted for 16S rRNA gene amplification and phylogenetic
      analysis after a comparison of antitumor activities, morphological, physiological
      characteristics and whole cell amino acids analysis. The results suggested that
      strain YIM 80139 is a member of a known Streptomyces species S. griseus, while
      strain YIM 80038 may represent a potential new Streptomyce species, and that the
      other 6 strains may represent 4 potential new species of the genus Nocardiopsis.
      The results presented above showed that actinomycetes isolated from saline and
      alkaline samples are important resources for bioactive compounds, and the
      abundant microbial diversity in the saline and alkaline environments in the
      Qinghai Province, Northwestern China is attractive for further investigation.

PMID- 18062245
TI  - Isolation of Photobacterium damselae subsp. piscicida from diseased tongue sole
      (Cynoglossus semilaevis Gunther) in China.
AB  - During the summer of 2006, an epizootic occurred among cultured tongue sole
      (Cynoglossus semilaevis Gunther) in a fish farm in Qingdao, China. The diseased
      tongue sole exhibited haemorrhaging of the basal fin, yellowed kidney and
      ulceration of the body surface. A Gram-negative,rod shaped bacterium (designated
      strain WY06) was isolated from the gall bladder of diseased fish. Pathogenicity
      assays revealed that WY06 was virulent to tongue sole and zebrafish (Danio rerio)
      by intraperitoneal injection challenge, with the LD50 being calculated as 5.5 x
      10(3) cfu/g of fish (5.2 x 10(5) cfu/fish) and 1.9 x 10(3) cfu/g of fish (8.9 x
      10(2) cfu/fish) respectively. The 16S rRNA gene sequence of strain WY06
      demonstrated high similarity (99%) with Photobacterium damselae subsp. piscicida.
      Phylogenetic analysis showed a clear association of strain WY06 with P. damselae
      subsp. piscicida. Additional evidence of the identification included in
      morphological, physiological and biochemical data. The pathogen was sensitive to
      cifuroxime (30 microg) and ceftriaxone sodium (30 microg). Present study
      describes P. damselae subsp. piscicida from diseased fish for the first time in
      China.

PMID- 18062246
TI  - [Reclassification of the four China isolated strains of the pathogen for
      contagious caprine pleuropneumonia].
AB  - Contagious caprine pleuropneumonia (CCPP) is caused by Mycoplasma capricolum
      subsp. capripneumoniae (Mccp). The aims of this study were to identify 4 Chinese
      isolated strains employing molecular methods and to determine the appropriate
      subspecies classification of these strains. Three genome fragments (A, B and C)
      from each strain were amplified and then transformed into plasmids. The inserted
      fragments were sequenced and analyzed by comparison with six members of the
      Mycoplasma mycoides cluster. Cleavage of the PCR products of the 4 strains with
      PstI yielded three fragments 548, 420 and 128bp in length, just like strain F38.
      The other M. mycoides cluster members had only 2 fragments of 428 and 128bp.
      Homology analysis of fragment B indicated that the 4 strains exhibited 99.5%
      homology with Mccp reference strain F38, 98.9% with M. capricolum subsp.
      Capricolum (Mcc) strain California Kid, and only 95.4% with Mmc strain ZZ. In
      fragment C, the 4 strains had 67.4% - 67.6% homology with Mmc PG3, 95.1% -98.6%
      with Mcc strains 8601-50 and California Kid, 99.6% - 99.8% with Mccp strains
      97097ET, Gabes and F38. The analysis revealed that 4 pathogeny strains, 87001,
      87002, 367, 1653, isolated from China are more closely related to Mccp than to
      Mcc. Therefore the pathogeny of CCPP in China should be reclassified as Mccp.

PMID- 18062247
TI  - [Identification of porcine reproductive and respiratory syndrome virus regulation
      sequence in 3'-untranslated region].
AB  - Based on our established infectious clone of PRRSV, designated as pCBC2, a series
      of mutagenesis of 3'-untranslated region (3'-UTR) at primary structure and
      secondary structure level were constructed. Then the full length mutant clones
      were transfected into MARC-145 cells, from which the influences of the discrete
      3'-UTR mutation on PRRSV replication and transcription were analyzed. The
      properties of the rescued mutant viruses were then further characterized by
      Northern Blot and plaque morphology analysis. Our results demonstrated that PRRSV
      could tolerate more than 41 nucleotides deletion and 23nt insertion in the 3'
      UTR, however, minor changes in the conserved stem loop region destroyed virus
      infectivity. To sum up, the stem-loop structure was essential for virus
      viability, but 5' end of the 3'-UTR tolerates certain level of nucleotide
      deletion or insertion. This is the first report to define the essential sequence
      and secondary structure for PRRSV genome replication and it is useful for future
      research about the regulation element.

PMID- 18062248
TI  - [Characterization of pcr2 gene of Pseudomonas aeruginosa].
AB  - Type III secretion system (TTSS) is an important virulence factor encoding by
      pseudomonas aeruginosa. About 40 genes are involved and they function as
      structure proteins, chaperons, regulators, and effectors proteins, respectively.
      Although some genes have been studied previously, functions of many genes
      remained unknown. Pcr2 gene is the third gene of popN operon that is one of the
      five operons of the TTSS gene clusters. Its functions were investigated in this
      study. First, by characterization of the phenotypes of pcr(2-) mutant, we found
      that the abilities of secreting or translocating effectors proteins were
      significantly damaged in the absence of Pcr2 protein, suggesting that Pcr2
      protein involved in both the secretion and translocation processes of TSS.
      Second, evidences were provided that no PopN protein was detectable in
      supernatant of pcr(2-) mutant culture. Combined with the data from the bacterial
      two-hybrid system, we can conclude that Pcr2 protein might function as part of a
      chaperone complex for the PopN protein. Third, Pcr2 protein was found secreted in
      a TTSS-dependent manner, suggesting that secreted Pcr2 may play a role in the
      TTSS needle biogenesis.

PMID- 18062249
TI  - [Construction of the Man8 GlcNAc2 glycosylation Saccharomyces cerevisiae mutant
      strain].
AB  - In Saccharomyces cerevisiae, protein glycosylation passed two different N-linked
      modification pathways after the export of predominantly Man8 GlcNAc2-containing
      glycoproteins from ER to the Golgi. The core oligosaccharide undergoes maturation
      in the Golgi resulting in a Man8-13 GlcNAc2 structure. Alternatively, core
      structures may be hypermannosylated with up to 200 mannose residues composing of
      a backbone of alpha1,6-mannosyl residues with branched alpha1, 2- and alpha1,3
      mannosyl side chains. Mnn1p and Och1p play an important role in this process. The
      null disruption of MNN1, OCH1 was replaced by the S. cerevisiae URA3, HIS3,
      respectively. To characterize the N-glycosylation in the mnn1 och1 mutant,
      mannoproteins were obtained by hot citrate buffer extraction after the mnn1 och1
      cells were crumbled. The extracted mannoprotein was precipitated by ethanol, and
      further purified by concanavalin A-sepharose 4B. The N-oligomannose saccharides
      were released from mannoprotein by PNGase F digestion, and then peptides and
      detergents were removed by passage through ion exchange columns. For desalting,
      glycans were applied to porous graphitic-carbon cartridge. 2-aminopyridine
      pyridylaminated sugars were profiled and purified by size fractionation HPLC with
      Shim-pack cle-NH2 column, and result showed dominantly a single peak. MALDI
      TOF/MS analysis ofthis peak revealed that its molecular weight was 1796.5Da,
      which corresponds to the calculated mass of Man8 GlcNAc2-PA. These results
      indicated that disruptions of MNN1 and OCH1 eliminated the hypermannosylation of
      the N-linked glycans, and glycoproteins were glycosylated with a single core type
      glycan, Man8 GlcNAc2, in the mnn1 och1 mutant.

PMID- 18062250
TI  - [Cloning and expression of F18 fimbrial operon gene clusters from enterotoxigenic
      Escherichia coli and their bioactivity].
AB  - The fed operon gene clusters with each size of 5.6kb, encoding the F18ab or F18ac
      fimbriae, was amplified respectively by high fidelity PCR using the genomic DNA
      templates from F18 fimbriae E. coli strains 107/86 or 2134P. The PCR products
      with the restriction enzyme sites at each end were digested and then cloned into
      the vector pET-22b (+), the recombinant plamids with the inserts of both type of
      fed gene clusters were constructed and screened, further confirmed by the means
      of combination with restriction endonuclease analysis and sequencing. The both
      types of fimbriae F18ab and F18ac were expressed efficiently in the E. coli BL21
      (DE3) after proper concentration of IPTG induction. Expressed fimbriae were
      revealed and confirmed by transmissible electromicroscope observation. The both
      fimbriae F18ab and F18ac were isolated and purified from the recombinant E. coli,
      and only a single major band of protein with size of approximately 15kDa was
      visualized in Coomassie blue-stained gels after SDS-PAGE. The rabbits sera with
      high titer of anti-F18 fimbriae were detected after being immunized with the
      purified F18ab or F18ac fimbriae. The results of combination of agglutination
      assay with Western blotting showed that the sera directed against both fimbriae
      F18ab and F18ac reacted positively with the F18 fimbriae from both wild E. coli
      107/86 and 2134P. Small intestine epithelial cells with F18 fimbriae receptors,
      which were from post-weaning piglets with the genotypes of FUT1 gene both
      M307(GG) and M307(AG), were prepared and tested for the adherence of E. coli
      expressing F18 fimbriae under the microscopic examination. Adhesion and adhesion
      inhibition test showed both of the recombinant E. coli expressing F18ab or F18ac
      fimbriae respectively could adhere to the jejunal epithelial cells in vitro as E.
      coli 107/86 and 2134p did. The both of anti-sera directed against fimbriae F18ab
      or F18ac respectively can efficiently inhibit the fimbriae-mediated post-weaning
      piglet jejunal epithelial cells adherence to both the recombinant E. coli
      (expressing F18ab or F18ac fimbriae) and wild type E. coli (107/86 and 2134P).

PMID- 18062251
TI  - [Isolation of avian Escherichia coli and PCR detection of their F1 and HPI
      genes].
AB  - To further investigate into the prevalence of F1 fimbriae and high pathogenicity
      island (HPI) in avian Escherichia coli, a total of 69 bacteria isolates (29 from
      geese and 40 from chickens) were obtained from deceased poultry and characterized
      to be Escherichia coli by gram staining, culture characterizing and bio-chemical
      testing. Two sets of primers were designed or analyzed with DNAStar software
      based on the F1 and HPI sequences that deposited in GenBank and synthesized by
      Sangon Biological Engineering Technology and Service Co. Ltd. (Shanghai, P. R.
      China). All the primers were tested for their specificities by using reference E.
      coli strains, and it is confirmed that the PCR using primers F1-F and F1-R could
      identify F1+ E. coli, as well as the PCR using primers irp-F and irp-R could
      identify HPI+ E. coli. All the isolates were submitted to PCR detection, and the
      data shows 46 isolates (66.7%) were F1-positive, 10 isolates (14.5%) were F1+ HPI
      positive and 2 isolates (20.0%) were HPI-positive. Furthermore analysis indicated
      that the prevalence of F1 and HPI have no different between the isolates from
      geese and chickens, and no different among the isolates from different tissue,
      such as liver, lung and duodenum. In addition, all the 69 E. coli isolates
      serological typed, and the results show that the isolates from geese were
      belonged to O26 (25.0%), O78 (12.5%), O18 (12.5%) and O117 (12.5%), while E coli
      from chickens were fell into O109 (37.5%), O24 (18.75%), O18 (12.5%), O139
      (12.5%) and O78 (6.25%). Seven kinds of antibiotics were tested on 11 isolates,
      and it revealed that most isolates were sensitive to cefazolin, nitrofurantoin
      and gentamycin, while resistant to lincomycin, tetracycline and polymycin B.

PMID- 18062252
TI  - [Replicative kinetics of classical swine fever virus in PK-15 cells].
AB  - In order to understand the replication kinetics of classical swine fever virus
      (CSFV) in in vitro cells PK-15 cells were seeded in 96-well tissues culture
      plates. After overnight incubation at 37 degrees C in 5% CO2 environment when
      growing to 80% confluence, the cells were infected with CSFV strain Shimen at 100
      TCID50 per well. At various time post infection (p.i.) the replication of the
      virus in the cells were analyzed repectively by detection of viral antigen using
      indirect immunofluorescent assay (IFA), RNA replication using reverse
      transcription real-time PCR and viral production using titration of TCID50. In
      the results of the IFA the viral antigen could be detected as early as 8hrs p.i.
      and at 72h hrs p.i. almost all cells showed positive staining, the real-time PCR
      showed that the synthesis of viral genomic RNA was gradually increased between 8
      24 hrs p.i. and reached its peak at 72 hrs p.i.. However, the synthesis of
      negative strand RNA was maintained at a low level for a whole period of culture
      although it could be detected at 8hrs p.i.. Titration of TCID50 demonstrated that
      the production of live virions increased at 8h and peaked between 48 - 72 hrs
      p.i. without significant lose of titer.

PMID- 18062253
TI  - [Genome sequence analysis of an H3N2 subtype swine influenza virus isolated from
      Guangdong province in China].
AB  - An H3N2 subtype swine influenza virus, A/Swine/ Guangdong/01/2005 (H3N2), was
      isolated from pigs with influenza-like signs in Guangdong province in 2005.
      Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify the
      gene segments for sequencing analysis. Phylogenetic analysis showed that the
      hemagglutinin(HA) gene of A/Swine/ Guangdong/01/2005 shared high degree of
      sequence identity with those of H3N2 viruses isolated from swine in Guangdong
      province from 2003 to 2004 and H3N2 viruses isolated from human in New York in
      the end of 1990s. The neuraminidase (NA) gene of this H3N2 swine virus had high
      degree of sequence identity with those of H3N2 viruses isolated from human in New
      York from 1998 to 2000. While the nonstructure (NS) gene and matrix (M) gene of
      this H3N2 swine virus showed high degree of sequence identity with those of
      classical H1N1 swine influenza viruses. These results indicated that the M and NS
      gene might originate from the H1N1 subtype swine influenza viruses, while the HA,
      NA and other genes of this H3N2 subtype swine influenza virus might originate
      from the H3N2 subtype human influenza viruses. Therefore, the H3N2 swine
      influenza virus, A/Swine/Guangdong/ 01/2005 (H3N2), is a recombinant of H3N2
      human influenza virus and classical H1N1 swine influenza virus.

PMID- 18062254
TI  - [Expression profile analysis of host HeLa cells invasived by Shigella flexneri
      2a].
AB  - The changes of genes expression in HeLa cell during the invasion with Shigella
      species for 1h and 3h were analyzed by cDNA microarrays. The data showed that the
      expression levels of 752 genes were altered twice or greater as compared with the
      control 509 of them were up-regulated, and 306 were down-regulated. It was
      supposed that some signal pathways in HeLa cell were activated, then many genes
      were induced, and at last comprehensive cell responses were produced, so that
      HeLa cell could prevent against Shigella species infection. Two striking
      difference cDNA fragments TNFR 1B and ERBB2, which were up-regulated in the host
      epithelial cell during Shigella infection, analyzed expression by real time RT
      PCR as determined by cDNA arrays. We suggested they play important roles in
      response to the invasive S. flexneri 2457T. Based on the results of gene
      expression alterations, the molecular pathogenic mechanism of Shigella species
      could be greatly and deeply understood, and the strategy for prevention against
      and treatment for shigellosis would be formed.

PMID- 18062255
TI  - [Extraction of mitochondrial DNA of Tilletia indica Mitra and application of the
      ATP6 gene on fungal phylogenetic analysis].
AB  - Tilletia indica Mitra, an important pest around the world which is the causative
      agent of Karnal Bunt of wheat, was very close to Tilletia walkeri
      phylogenetically and morphologically. 69.6 ng mitochondrial DNA (mtDNA) of
      Tilletia indica obtained from 6.4 mg total DNA by the method of CsCl/bisbenzimide
      density gradient ultracentrifugation can be used for electrophoresis, cloning,
      enzyme restriction analysis and PCR amplification. The ATP6 gene sequence was
      cloned from the fragment of mtDNA and sequenced for analysis of phylogenetic tree
      with the other related sequences in GenBank by the software PAUP to reveal the
      phylogenetic relationships within the Tilletia species.

PMID- 18062256
TI  - [Bioactivity of endophytic actinomycetes from medicinal plants and secondary
      metabolites from strain D62].
AB  - It is believed that genetic recombination of the endophytes with the hosts that
      occurred in evolutionary time could result in some endophytes producing certain
      phytochemical originally characteristic of the host. Based on this widely
      accepted hypothesis, there have been increasing research efforts focused on
      screening for novel natural products from endophytes. In this study,
      antimicrobial and antitumor activities of 165 actinomycetes isolated from
      medicinal plants collected from Xishuangbanna were tested by agar diffusion
      method and WST-8 assay respectively. The results showed that over 42% of the
      isolates exhibited antagonism against pathogenic strains, and 54.5% displayed
      excellent inhibition against mouse melanoma cell line B16 or/and human alveolar
      epithelial cell line A549. These results are superior to those of soil
      actinomycetes, indicating tremendous potential of endophytic of actinomycetes for
      exploration. Six compounds that had both antimicrobial and antitumor activities
      were separated and purified from isolate Streptomyces sp. D62 by resin
      adsorption, silica-gel column and sephadex chromatography, etc. On the basis of
      spectral analyses, they were identified as antimycin A4a (1), antimycin A7a (2),
      antimycin A2a (3), antimycin A1a (4), 10-hydroxy-10-methyl-dodec-2-en-1,4-olide
      (5) and 6-(2-(4-aminophenyl)-2-oxoethyl)-3,5-dimethyl-tetrahydropyran-2-one(6),
      with the last one defined as a novel compound. Based on all these results, it is
      convinced that endophytic actinomycetes are a promising resource for bioactive
      natural product discovery.

PMID- 18062257
TI  - [Screening and function analysis of a cyclohexanone-degrading bacterium CN1 from
      deep sea sediment].
AB  - Micrococcu luteus CN1 was found to be able to utilize cyclohexanone well from the
      strains originally isolated from Pacific Ocean sediment. The optimum conditions
      for its growth were determined as 25 degrees C -37 degrees C, pH 8, salinity 6%.
      It could survive in the medium with high concentration of cyclohexanone ( > 44%
      V/V), and grew most vigorously in medium with 16.7% (V/V) cyclohexanone. CN1
      could transform cyclohexanol to cyclohexanone which could be further degraded and
      mineralized quickly. This indicated the presence of cyclohexanol dehydrogenase
      and probable presence of cyclohexanone monooxygenase. With degenerate PCR for
      cloning part of cyclohexanone monooxygenase gene, the DNA fragment of 450bp was
      gotten. Amino acid sequence analysis showed that it owned the conserved sequence
      of the Baeyer-Villiger monooxygenase family and had the highest homology of 80%
      with cyclohexanone monooxygenase from Arthrobacter sp. BP2, only 53% with that
      from Acinetobacter sp. NCIMB 9871 which had been the most deeply investigated. So
      far as we know, both cyclohexanol and cyclohexanone degradation resorted to
      cyclohexanone monooxygenase. So this gene should be responsible for cyclohexanone
      degradation in CN1. All the cyclohexanone-degraders previously reported could
      degrade cyclopentanone, but, CN1 did not degrade cyclopentanone. This indicated
      that cyclohexanone monooxygenase in CN1 was special. Additionally, it was found
      for the first time that cyclohexanol could inhibit cyclohexanone degradation to
      certain degree in CN1.

PMID- 18062258
TI  - [Study on cooperating degradation of cypermethrin and 3-phenoxybenzoic acid by
      two bacteria strains].
AB  - The microbial cooperated reaction is one of the most important forms of microbial
      degradation of organic pollutants. Although there were many research reports of
      cooperating degradation, less report on the microbial cooperated of pyrethroid
      degradation to be found. We have isolated one degrading-bacteria strain named
      CDT3 for degradation of cypermethrin, which can degraded the cypermethrin into 3
      PBA and DCVA. At the same time, we also isolated another degrading-bacteria
      strain named as PBM11, which could get multiplication on 3-PBA as its C source
      and energy source. The cooperative degradation process of cypermethrin and 3
      Phenoxybenzoic acid (3-PBA) using the two degrading-bacteria strain CDT3 and
      PBM11 was investigated. An obvious inhibition to the cypermethrin degrading
      bacterium strain CDT3 (Rhodococcus sp.) by its metabolic mediate 3-PBA was found;
      meanwhile there is no effect on the growth of 3-PBA degrading-bacterium strain
      PBM11 (Pesudomonas sp.) when the concentration of cypermethrin was lower than 200
      mg/L. The degradation rate of cypermethrin by both strain CDT3 and PBM11 was
      higher than that by CDT3 alone. The biomass of PBM11 increased along with the
      degradation of cypermethrin and 3-PBA, but that of CDT3 not. There was no the
      accumulation of 3-PBA when the simultaneous addition of strain CDT3 and PBM11,
      however, an obvious one within 24h if inoculation of strain PBM11 was later 24h
      after inoculation of strain CDT3, Subsequently the 3-PBA was degraded rapidly by
      strain PBM11. The strains CDT3 and PBM11 showed some characteristics of co
      metabolism, however it is not actual degradation form of co-metabolism. For
      examples, although the degrading sub product of cypermethrin by CDT3 could be
      utilized, the multiplication of PBM11 could not enhance the multiplication of
      CDT3, implied there is no obvious relationship between the two strains. Also, to
      add PBM11 could eliminate the inhibition of 3-PBA to CDT3. Thus, the cooperating
      degradation of strains CDT3 and PBM11 could promote the degradation of
      cypermethrin as well as eliminate the residues of middle products. The present
      research results provide new evidence for the theory of cooperated degradation,
      but a further research may be necessary.

PMID- 18062259
TI  - [Screening for autoinducer synthase gene in Sinorhizobium meliloti and analysis
      of the autoinducer produced by recombinant expression in Escherichia coli].
AB  - The plasmid pJZ290 containing mariner transposon was used to mutagenize
      Sinorhizobium meliloti and 3000 transposon insertion mutants were subsequently
      screened for autoinducer-deficient (AI-deficient) mutants. One AI-deficient
      mutant YW1 was obtained by quantitative activity assay and qualitative TLC
      detection. In an effort to characterize the transposon insertions of autoinducer
      deficient mutant YW1, we performed an arbitrary PCR and sequencing techniques to
      identify insertion sites. The sequence analysis result showed that the transposon
      inserted between the 277th bp and the 278th bp of one 621bp ORF in autoinducer
      deficient mutant YW1. The 612-bp ORF encodes a putative protein of 206 amino
      acids that is highly homologous (99% identity) to AHL-synthase traI of
      Sinorhizobium medicae WSM419. Cloned into the broad host range expression vectors
      pYC12 and transformed into Escherichia coli DH5alpha, the putative AI synthase
      gene was overexpressed in E. coli, and four different autoinducers could be
      detected in the supernatant of the positive recombinant strain by TLC, among
      which the two AHL molecules that were deficient in AI-deficient mutant YW1 could
      be found. All of these showed that the 621bp ORF was an AI synthase gene. This
      study paved the way of further studying quorum sensing systems in S. meliloti.

PMID- 18062260
TI  - [Cloning, expression and sequence analysis of chiA, chiB in Bacillus
      thuringiensis subsp. colmeri 15A3].
AB  - Two DNA fragments encoding chitinase A and B were amplified from total genomic
      DNA of Bacillus thuringiensis subsp. colmeri 15A3, and then ligated with pUCm-T
      cloning vector. The recombinant plasmids pUCm-chiA and pUCm-chiB were transformed
      into Escherichia coli XL-Blue respectively. Both chiA and chiB were successfully
      expressed in E. coli with their natural promoters independent of any chitin.
      Additionally, the expressed ChiA and ChiB could be secreted from E. coli cells.
      It was proved that two chitinases were constitutively expressed in strain 15A3.
      The nucleotide sequence of chiA (GenBank Accession Number: EF103273) with a
      length of 1426bp included an open reading fram(ORF) of 1083 bp encoding for a
      protein of 360 amino acids . The deduced amino acid sequence showed that the
      mature protein ChiA with a predicted molecular mass of 36kDa consisted of a
      single catalytic domain. The nucleotide sequence of chiB (GenBank Accession
      Number: EF103273) with a length of 2279 bp included an ORF of 2031bp encoding for
      a protein of 676 amino acid residues. The deduced amino acid sequence showed that
      the mature protein ChiB with a predicted molecular mass of 70.6kD was composed of
      three domains: catalytic domain, chitin-binding domain and fibronectin type III
      like domain. The comparison of their upstream sequences informed that there were
      differences between putative promoters of chiA and chiB.

PMID- 18062261
TI  - NsdB, a TPR-like-domain-containing protein negatively affecting production of
      antibiotics in Streptomyces coelicolor A3 (2).
AB  - Tetratricopeptide repeat (TPR) domains usually mediate protein-protein
      interactions. NsdA, one of the 70 proteins containing TPR-like domains in
      Streptomyces coelicolor A3 (2), was previously found to negatively control
      sporulation and antibiotic production. Here we show that elimination of SCO7252,
      which encodes another of these proteins, also caused overproduction of two
      antibiotics, actinorhodin and CDA, but did not affect morphological
      differentiation. Disruption of SCO1593, encoding another of the family, had no
      obvious phenotypic effects. In surface-grown cultures, expression of SCO7252,
      which was named nsdB, was initiated at about 30 h, like that of nsdA. Analysis in
      silico of the 70 predicted TPR-like-containing proteins of S. coelicolor showed
      that 32 of them contained only TPR-like domains, and 25 of the remainder
      contained additional DNA-binding domains, implying that they might control gene
      expression directly.

PMID- 18062262
TI  - [Cloning and analysis of the Vibrio harveyi dam gene].
AB  - The DNA adenine methylase (dam) gene was cloned by degenerate PCR from Vibrio
      harveyi strain T4. The gene was 840bp in length and encoded a putative protein of
      279 amino acids that shared relatively high homology with the Dam of other
      Vibrios, especially with that of V. parahaemolyticus (96% in identity). The V.
      harveyi dam gene was subcloned into plasmid pBR322 and the resulting plasmid pBD
      was introduced into the E. coli strain ER2925 in which the dam gene had been
      knocked out. Dpn I, Dpn II, and Sau3A I restriction enzyme analysis of the
      genomic DNA of ER2925 transformed with pBD indicated that the cloned V. harveyi
      dam gene could functionally complement the E. coli dam mutant and methylate E.
      coli chromosome at the GATC sites. The 3251 bp upstream region of V. harveyi dam
      was obtained by genome walking and analyzed at the sequence level. It was found
      that this 3251 bp region contained two complete open reading frames (ORF): one
      was of 1101 bp in length and the other was of 1503 bp in length. The predicted
      amino acid sequence of ORF1101 shared 91% identity with the 3-dehydroquinate
      synthase of V. parahaemolyticus. The amino acid sequence of ORF1503 shared 80%
      identity with V. parahaemolyticus DamX. A truncated ORF was found at the upstream
      of ORF1101, encoding 169 amino acids that shared 94% identity with the shikimate
      kinase of V. parahaemolyticus. These three genes, together with dam, were
      arranged in the order of shikimate kinase-3-dehydroquinate synthase-damX-dam. The
      region immediate upstream of the V. harveyi dam structural gene was cloned in
      three fragments of different length: 78bp, 112 bp and 477bp (named P78, P112, and
      P477, respectively) and tested for promoter activity. The results showed that,
      while all the three fragments had detectable promoter activities, the activity of
      P78 appeared to be higher than that of P112 and P477.

PMID- 18062263
TI  - [Cloning, expression and characterization analysis of the arginine deiminase of
      Streptococcus suis of China isolates].
AB  - PCR analysis demonstrated the presence of the ad gene in all 29 S. suis strains
      tested, but none of the seven S. equi subsp. zooepidemicus strains. The fragment
      of ad gene of virulent isolate SS2-HA9801 was later cloned into pBAD/Myc-HisC
      vector via restriction endonuclease and then transformed into host strain TOP10.
      A recombinant protein of 47000Da was highly expressed after induced by L-ararose
      and purified by Ni-nitrilotriacetic acid affinity chromatography. Western
      blotting demonstrated that the recombinant protein can reacted to the polyclonal
      antibody raised against whole-cell protein of SS2-HA9801, which suggested that it
      possessed some immunogenicity and may be important for further research.
      Enzymatic assay revealed that the optimum temperature for its activity is 37
      degrees C and pH is 6.5. Studies with class-specific inhibitors supported the
      assignment of a sulfhydryl enzyme with some metallo class characteristics.

PMID- 18062264
TI  - [Cloning and expression of nematicidal crystal protein gene cry6Aa of Bacillus
      thuringiensis].
AB  - On the basis of the sequencing of the N-terminal amino acid of the crystal
      protein, a nucleotide acid fragment harboring a novel nematicidal gene cry6Aa2
      was obtained from Bacillus thuringiensis strain YBT-1518. This fragment contains
      two ORFs: orf1 and orf2, while a "stem-loop" exists between orf1 and orf2. BLAST
      showed the similarity of orf1 nucleotide acid sequence with cry6Aa1 is 98%, and
      has been deposited in the Genbank database (Acc. No. AF499736). The cloning
      fragment was transferred to crystal negative mutation strain BMB171 by E. coli-Bt
      shuttle vector pHT304. A 54kDa protein with similarity to strain YBT-1518 was
      detected in recombinant strain, and rice shaped crystal was detected with
      transmission electron microscope. Bioassay indicated the LC50 of recombinant
      strain against second lavae juvenile of Meloidgyne hapla is 9.47 microg/mL,
      nearly equal to the original strain YBT-1518 (10.74 microg/mL).

PMID- 18062265
TI  - [The diversity of alkane degrading bacteria in the enrichments with deep sea
      sediment of the South China Sea].
AB  - Deep sea sediment samples of the South Sea of China were used for isolation and
      biodiversity examination of hydrocarbon degrading bacterium. 48 isolates were
      obtained from the enrichments with hexadecane as the sole carbon sources. Among
      them, 27 isolates were capable of degrading alkane; and 4 could produce
      biosurfactant significantly as determined by the surface tension measurement. 2
      isolates belonging to Dietzia maris lowered water surface tension to 33 mN/m.
      This is the first report about D. maris in biosurfactant production. The results
      of polymerase chain reaction (PCR) followed by Denaturing Gradient Gel
      Electrophoresis (DGGE) and DNA sequencing suggested that Bacillus was the
      dominant member in the hexadecane enriched communities. Isolates of Bacillus
      aquimaris were demonstrated to be the most predominant degraders in all 7 samples
      at 2 sampling sites. In addition, Sporosarcina, Halomonas and Brevibacterium were
      also found as one of the dominant members in some samples. Therefore, species of
      Bacillus might play an important role in alkane degradation in the sediments of
      the sampling sites.

PMID- 18062266
TI  - Genes encoding the Vibrio harveyi haemolysin (VHH)/thermolabile haemolysin (TLH)
      are widespread in vibrios.
AB  - V. harveyi VHH haemolysin, which shows high homology to the TLH haemolysin (the
      identities of their deduced amino acid sequences are up to 85.6%), is a putative
      virulence factor to marine cultured fish. A VHH probe, which is specific to V.
      harveyi vhhA haemolysin gene, was used to screen EcoR I digests of total DNA from
      57 vibrio strains, including 26 vibrio type strains, 20 V. harveyi isolates and
      11 V. parahaemolyticus isolates. As a result, 1 strong hybridisation band was
      detected in 13 type strains, including 2 of Vibrio alginolyticus, 2 of V.
      harveyi, and 1 strain each of Grimontia hollisae, V. campbellii, V.
      cincinnatiensis, V. fischeri, V. mimicus, V. natriegens, V. parahaemolyticus, V.
      proteolyticus and V. logei. Also, 1 weak band was detected in 6 type strains,
      including V. anguillarum, V. aestuarianus, Photobacterium damselae subsp.
      damselae, V. fluvialis, V. furnissii and V. vulnificus. There was not any
      hybridization signal in other type strains. Also, vhh/tlh was present in all
      isolates of V. harveyi and V. parahaemolyticus. Moreover, 3 isolates of V.
      harveyi, i.e. VIB 645, VIB 648 and SF1, had duplicated vhh genes. The data
      indicates that vhh/tlh is widespread in vibrios, especially in V. harveyi related
      species and V. fischeri related species. To support this conclusion, the vhh/tlh
      homologue genes in V. anguillarum VIB 72, V. campbellii VIB 285, V. natriegens
      VIB 299 and V. harveyi VIB 647 were cloned and sequenced, and the deduced amino
      acid sequences showed high degree of identities to VHH (67% - 99%) and TLH
      haemolysin (69% - 91%). This study will help us to identify the role of vhh/tlh
      haemolysin gene in the pathogenicity of vibrios.

PMID- 18062267
TI  - [Improved culturability of soil bacteria using proper combination with various
      culturing medium].
AB  - To isolate more unique and previously unrecognized bacteria in soil samples, the
      culture difference under three incubation modes was investigated by using
      trophic, low-nutrient broth and soil extract as growth medium. Plate count proved
      that the oligotrophic medium resulted in a slow growth and consecutive colony
      formation over the course of incubation. On the 5th day, the most number of
      colony-forming unit was found on trophic LB and low-nutrient R2A, which was
      approximate 5 times as many as that isolated on 0.1 x LB. Of the 7 media, LB
      broth harvested the maximum bacterial communities, and novel species could be
      isolated as the nutrient was diluted to appropriate extent. The DGGE patterns of
      oligotrophic and rich nutrient culture collection displayed low similarity,
      however, the bands at various lanes exhibited complementary effect. When
      cultivated with static flask, LB and R2A media obtained more bacterial species,
      which concluded most species isolated by the other five media. Under the test
      tube incubation mode, the most species was also found in LB medium except some
      appeared only on R2A and TSB. Apparent bacterial communities difference could be
      detected between R2A, LB and TSB media. The experiment data may contribute much
      to the special medium design as well as improvement of bacterial culturability by
      using proper medium.

PMID- 18062268
TI  - [Microbial diversity in scorpion intestine (Buthus martensii Karsch)].
AB  - Scorpion is an important officinal animal, and has a high nutritional value. In
      this study, the culture-independent and culture-dependent methods were used to
      investigate the microbial diversity in the scorpion's intestine. Results based on
      culture-independent method showed the bacteria to be related to alpha, beta,
      gamma-proteobacteria. Bacteria isolated by the culture-dependent method were high
      G + C, gram-positive bacteria. The genera Enterobacter, Serratia and Ochrobactrum
      were detected by both methods. To sum up the results from the two methods, the
      bacteria in scorpion intestine belong to 23 genera, which are Enterobacter,
      Serratia, Pseudomonas, Acinetobacter, Aeromonas, Citrobacter, Pedobacter,
      Delftia, Ralstonia, Ochrobactrum, Sphingomonas, Exiguobacterium, Gordonia,
      Nocardia, Rhodococcus, Janibacte, Kocuria, Micrococcus, Agromyces,
      Microbacterium, Agrococcus, Deinococcus, Ornithinimicrobium, and some uncultured
      species. The two methods have both advantages and shortcomings. However, when
      used simultaneously, they complement each other.

PMID- 18062269
TI  - [Pathogenicity and genomic sequence comparison of a chicken infectious anemia
      virus field isolate].
AB  - A field strain C14 of chicken infectious anemia virus (CAV) was isolated from a
      14 day-old broiler flock with growth runting syndromes. Antibody reactions to
      inactivated vaccines to avian influenza viruses (AIV) were suppressed in SPF
      chickens inoculated with C14 strain CAV at 1 day-old. Also C14 strain CAV and
      reticuloendotheliosis Virus demonstrated a synergism in immunosuppression when
      chickens were infected with both virus. The viral genomic DNA was amplified by
      PCR in 3 overlapped fragments and PCR products were cloned into T-vector plasmid
      for sequencing. The sequencing results indicated that the total genome of C14
      strain CAV was 2298bp, it contained 3 overlapped ORF and 1 non-coding regulation
      fragment. Its whole genome had 97.2% - 99.2% of homogeneity to other several
      published CAV reference strains. Sequence data indicated that there are many
      motifs in the non-coding area of about 400bp as the binding sites for
      transcriptional factors. All these motifs were very conservative. There were some
      mutations in 3 genes VP1, VP2 and VP3. Relatively, VP1 was less conservative than
      VP2 and VP3. Among different strains, mutations in these 3 genes were not
      correlated.

PMID- 18062270
TI  - [Mycoplasma genitalium lipid-associated membrane proteins induce human monocytic
      cell express proinflammatory cytokines and apoptosis by activating nuclear factor
      kappaB].
AB  - Designed to investigate the potential pathogenicity of Mycoplasma genitalium (M.
      genitalium) and its molecular mechanisms responsible for the induction of
      proinflammatory cytokines gene expression in human monocytic cells (THP-1)
      stimulated by lipid-associated membrane proteins (LAMPs) prepared from M.
      genitalium. THP-1 cells were stimulated with LAMPs to analyze the production of
      proinflammatory cytokines and the expression of mRNA was detected by RT-PCR. Cell
      apoptosis was detected in THP-1 cells by Annexin V-propidium iodide staining. The
      activity of transcriptional factors, NF-kappaB, was examined in THP-1 cells
      treated with LAMPs by EMSA. The effects of pyrrolidine dithiocarbamate (PDTC), an
      inhibitor of NF-kappaB, on the production of proinflammatory cytokines, the
      expression of mRNA and apoptosis were also examined in THP-1 cells treated with
      LAMPs. M. genitalium LAMPs stimulate THP-1 cells to produce TNF-alpha, IL-1beta
      and IL-6 in dose- and time-dependent manner. The mRNA levels and cell apoptosis
      are also downregulated in response to LAMPs stimulation and inhibited by PDTC
      treatment. M. genitalium LAMPs are found to trigger NF-kappaB activation, a
      possible mechanism for the induction of mRNA expression and the cell apoptosis.
      This study demonstrated that M. genitalium may be an important etiological factor
      of certain disease due to the ability of LAMPs to stimulated the expression of
      mRNA and apoptosis, which is probably mediated through the activation of NF
      kappaB.

PMID- 18062271
TI  - [Production of l-ephedrine and d-pseudoephedrine in recombined yeasts obtained by
      argon ion implantation mediated Ephedra genome DNA transformation].
AB  - The genome DNA from Ephedra glauca was randomly transferred into Hansenula
      anomala, respectively, by argon ion bombardment. Then, after screening by the
      motheds of bromothymol blue indicator selection, slant cultivation, l-ephedrine
      and d-pseudoephedrine copper chromic salt qualitative test and RP-HPLC
      determination, 3 strains, producing recombined yeasts were obtained, which can
      use glucose as a carbon source, NaNO3 as nitrogen source and be genetically
      stable. After cultivated in liquid medium for 72 hours and analyzed by the RP
      HPLC, the recombined strains can produce l-ephedrine 11.87 mg/L and d
      pseudoephedrine 4.11 mg/L excellular, d-pseudoephedrine 294.86 mg/g dry cell
      incellular, but l-ephedrine not detected incellular. The transformation
      efficiency of Ephedra genome DNA transferred into yeasts via argon ion
      bombardment was 0.65%. The effects of Ephedra genome DNA macromolecule integrity
      on yeast transformation system were discussed. The results shown that DNA
      macromolecule with integrated structure used as exogenous donor can obtain higher
      transformation efficiency than DNA macromolecule random fragments by ion
      implantation mediated DNA transformation. It was inferred that biosynthesis of l
      ephedrine and the d-pseudoephedrin were controlled by linked together genes or
      gene clusters.

PMID- 18062272
TI  - [Cloning and functional analysis of cysI gene involved in siderophores
      biosynthesis in Pseudomonas mosselii E1].
AB  - A siderophores-producing strain E1 was isolated from the rhizosphere of cotton.
      Its 16S rDNA is identical to that of Pseudomonas mosselii sp. nov. at 100% level.
      The suicide plasmid pRL1063a carrying Tn5-1063 was introduced into E1 by
      triparental mating and 1000 transposon insertion mutants were subsequently
      screened using CAS assay. One mutant deficiency in siderophores production was
      obtained, namely, E1-185. DNA sequences flanking Tn5-1063 of E1-185 was amplified
      by TAIL-PCR. According to the DNA sequencing results, it is found that Tn5-1063
      was inserted into cysI gene. The cysI of E1 is identical to that of Pseudomonas
      entomophila. L48 at 96% level, and similarity of amino acid sequences of their
      CysI is 97% . The cysI gene is required for the synthesis of cysteine. However,
      The ability in siderophores production of E1-185 on the plate of CAS with
      cysteine was recovered. It is indicated that cysI play an important role during
      the synthesis of siderophores. It was supposed that cysI is involved in the
      synthesis of acyl-S-PCPs, which is the key protein in the synthesis pathway of
      siderophores.

PMID- 18062273
TI  - [Influence of culture mode on bacterial cellulose production and its structure
      and property].
AB  - Acetobacter xylinum NUST4.2 has been applied in the studies to examine the
      production, structure and thermal property of bacterial cellulose (BC) produced
      in stationary culture and in the stirred tank reactor. These differences are as
      follows: BC yield reached 7.5 g/L in stationary culture for 6 days and its
      productivity was 0.052 g/L/h. BC production reached 3.13 g/L in the stirred tank
      reactor for 72h and its productivity was 0.043 g/L/h. SEM showed that there was
      almost no difference between network structure built of entangled cellulose
      ribbons produced in static culture and in the reactor. But the cellulose ribbons
      produced in static culture were a much more entangled and denser network with
      curved and overlapping cellulose ribbons in comparison with that one produced in
      the stirred tank reactor. Also the thickness of the cellulose ribbons seems to
      differ between the two BC samples, with the one from static culture distinguished
      by the slightly thinner ribbons. FT-IR revealed that there was no effect of
      stirring on the chemical structure of BC, but intermolecular hydrogen bond of
      cellulose was weakened. Furthermore, BC synthesized in static culture displayed
      I(alpha)-rich cellulose. XRD results indicated that no remarkable change in the
      cellulose crystallographic form of the BC samples. Nevertheless, BC produced in
      static culture was characterized by a higher crystallinity, higher I(alpha)
      content and higher crystalline size than cellulose that was produced in the
      reactor. All of these results revealed that stirring in the reactor interfere
      strongly in the process of nascent microfibrils crystallization, favoring the
      formation of smaller size microfibrils and increased I(beta), the more stable
      allomorph. Compared with cotton cellulose, the changes of thermal decomposition
      behavior in the BC samples were that BC produced in static culture displayed
      better thermal stability, but BC produced in the stirred reactor displayed better
      flame retarding.

PMID- 18062274
TI  - Comparison of virulence-associated traits between a UPEC strain HEC4 and a APEC
      strain E058.
AB  - Since avian pathogenic Escherichia coli (APEC) and human uropathogenic
      Escherichia coli (UPEC) may encounter similar challenges when establishing
      infection in the extra-intestinal locations of the hosts, they may share a
      similar content of virulence genes and capacity to cause disease. One APEC and
      one UPEC isolates were compared by their content of virulence genes and other
      traits. The two strains showed overlap in terms of their virulence genotypes,
      including their possession of certain genes associated with a large transmissible
      plasmid of APEC, and also shared some biochemical activities. Study of the
      pathogenicity of UPEC in chicks showed the similar symptoms and lesions compare
      to those caused by APEC. Based on these results, the potential whether APEC might
      serve as a reservoir of plasmid-linked and virulence genes for UPEC should be
      considered.

PMID- 18062275
TI  - [Construction and immunogenicity of an attenuated mutant of Actinobacillus
      pleuropneumoniae by insertional inactivation of apxIC].
AB  - Actinobacillus pleuropneumoniae is the aetiological agent of porcine
      pleuropneumonia. Apx toxin, an exotoxin secreted by A. pleuropneumoniae, is one
      of the most important virulence factors. To construct an avirulent mutant strain
      by inactivation of ApxI toxin, the apxIC gene of A. pleuropneumoniae serovar 10
      was inactivated by inserting a chloramphenicol resistance gene cassette into the
      downstream XhoI site of the apxIC gene for constructing the transfer plasmid. The
      transfer plasmid was introduced into the electrocompetent A. pleuropneumoniae
      serovar 10 for homologous recombination by electroporation. The mutant strain was
      obtained and identified by PCR and Southern blotting. The mutant strain was
      phenotypically identical to the parent strain except that it showed no haemolytic
      activity. The mutant strain was also able to secret the same ApxI toxin as the
      parent strain. In the intra-peritoneal mouse model, the virulence of the mutant
      strain decreased at least 100 fold compared with the parent strain. The mutant
      was evaluated as a potential vaccine using a vaccination-challenge trial in which
      pigs were given two intra-nasal doses of the mutant with 14 days' interval and
      then challenged 14 days after the last vaccination with A. pleuropneumoniae
      serovar 1 and serovar 10 reference strains respectively. The death number and
      lung lesion score in the vaccinated pigs given the serovar 1 challenge were
      obviously lower than those in the unvaccinated pigs. And the lower lung lesion
      score was also observed in the vaccinated pigs challenged with serovar 10. And
      the positive numbers of A. pleuropneumoniae re-isolation and PCR detection showed
      the same consistency. The vaccination-challenge trial suggested that the mutant
      strain could offer partial cross-protection as a live attenuated vaccine against
      A . pleuropneumoniae infection.

PMID- 18062276
TI  - [Production of monoclonal antibodies to Cymbidium mosaic virus and application in
      orchids virus detection].
AB  - Three hybridoma cell lines, 2C6, 5B7 and 12G9, secreting monoclonal antibodies
      (McAbs) against Cymbidium mosaic virus (CymMV) were produced by fusing mouse
      myeloma cells (SP2/0) with spleen cells from BALB/ C immunized by the CymMV
      particles. The three McAbs could specifically react with CymMV. The titres of
      ascitic fluids of two McAbs are up to 10(-6) in I-ELISA. Isotypes and subclasses
      of the the three McAbs belong to IgG1. Isotypes of light strains of the three
      McAbs all belong to kappa. They were used in antigen-coated plate (ACP)-ELISA for
      CymMV detection, and ACP-ELISA could successfully detect 0.487 ng of purified
      CymMV or virus in plant sap diluted 1:10240. The presence of CymMV in field
      Orchids tissues was investigated with ACP-ELISA.

PMID- 18062277
TI  - [The heterologous expression and purification of membrane protein from
      Mycobacterium tuberculosis].
AB  - Membrane proteins fulfill a wide range of central functions in the cell, but
      their structure determination remains one of the great challenges in structural
      biology. The heterologous overexpression is a demanding task. Here, we provide an
      overview of recent advance to heterologous expression and purification of
      membrane protein from Mycobacterium tuberculosis, whose membrane proteins
      represent the majority of the new potential drug targets in this bacillus, which
      is ranked as the number1 cause of infectious disease mortality in the world. A
      detailed structural and functional understanding of the membranes protein of
      Mycobacterium tuberculosis will be critical both for an understanding of the
      biology of infection and for the rational development of novel therapeutics. The
      procedures for functional expression followed by purification of membranes
      protein are reviewed here together with nonfunctional expression in inclusion
      bodies and subsequent refolding to produce functional proteins. The new
      expression systems, new approaches to soluble expression of recombinant proteins,
      new methods for membrane protein folding in vitro and new purification technology
      will provide a basis for choosing the best expression and purification protocol
      for a given membrane protein. The goal of this review is to aid researchers in
      the choice of a suitable expression system for their favourite proteins and make
      overproduction of functional membrane proteins becomes easier.

PMID- 18062278
TI  - [Study progress on compatible solutes in moderately halophilic bacteria].
AB  - Moderately halophilic bacteria which grow best in media with 3% to 15% salt
      constitute a heterogenous group of microorganisms which belong to different
      genera. These bacteria can inhabit the salt or soda lakes, coastal lagoons or man
      made salterns. Moderately halophilc bacteria living in higher saline environments
      can not only cope with high osmotic stress but also adapt osmotic shock in short
      time. To adapt to these environments, all the species make a osmoprotection by
      the accumulation a restricted range of low molecular mass molecules, small,
      organic compatible solutes, such as sugars, amino acids, betaines and ectoines.
      Therefore, the osmoadaptation of moderately halophilc bacteria is regulated by
      the so-called "compatible solute" strategy. Compatible solutes are operationally
      defined as organic osmolytes that can be amassed by the cell in exceedingly high
      concentrations without disturbing vital cellular functions and the correct
      folding of proteins. As a result, compatible solutes can make important
      contributions to the restoration of the turgor under conditions of low water
      activity by counteracting the efflux of water from the cell. In addition, they
      have a stabilizing, both in vivo and vitro, on the native structure of proteins
      and cell components. This mechanism has a minimal requirement for genetic change
      and a high degree of flexibility in allowing moderate halophiles to adapt to
      saline environment. In this review, the adaptation to saline environments, the
      variety and characteristic of compatible solutes, and the functional mechanism of
      moderately halophilic bacteria are reviewed and discussed.

PMID- 18062279
TI  - [Development of noroviruses].
AB  - Noroviruses (NVs) were one of the new borne viruses, which was found firstly in
      the Unit States of America in 1972 and reported in China in 1995. The main food
      borne viral pathogens affect people badly and cause the epidemic acute
      gastroenteritis in all kinds of people. And to this day, however, no cell lines
      and animal models have been found, which has hampered the study of these viruses.
      With the progress of the molecular biology and other subjects, the genomes of
      different NVs were sequenced, and the proteins of the viruses were expressed in
      vitro by the eukaryotic and prokaryotic expression systems respectively.
      Therefore, the novel knowledge and ideas on NVs were developed quickly in the
      character of these kinds of viruses. In this article, the NVs were described
      systematically, such as the structure of genomes and function of these
      nucleotides, organization and function of proteins, application and development
      of detecting and accumulation of epidemiology. Furthermore, the majority of
      researchers were interested in and focused on the study of protein and the
      detection of viruses. The progress and obstacles in this field were also
      involved. In additional, the suggestions were mentioned about the molecular
      evolution, detection and multiplication system in vitro on the viruses.

PMID- 18062280
TI  - [Clinical analysis of extramedullary plasmacytomas in the head and neck].
AB  - OBJECTIVE: To summarize the clinical features and the experiences of diagnosis
      and treatment of extramedullary plasmacytomas (EMPs), and to enhance the cure
      rates of EMPs. METHOD: Clinical data of 8 patients with EMPs in head and neck,
      who treated in our hospital from Jan. 1990 to Dec. 2004, were reviewed. Of 8
      cases, 3 cases with the tumors occurred in nasal cavities, 1 in maxillary sinus,
      2 in nasopharynx, 1 in posterior wall of oropharynx. RESULT: Eight patients who
      were all pathologic confirmed EMP accepted surgical resections of the tumors, and
      4 of 8 cases were boosted radiation therapy post-operation. Four cases were still
      alive disease-free for more than 1, 5, 10 and 12 years after treatments,
      respectively. One died of local recurrence in 2 years, 1 died of multiple myeloma
      in 3 year, and 1 died of heart attack in 2 years after treatments, respectively.
      One lost follow-up. CONCLUSION: EMPs in head and neck are low potential
      malignancy tumors. The diagnosis of EMPs mainly depends on clinical
      manifestations and pathological results. Surgery and radiation therapy are the
      main treatments for EMPs in head and neck.

PMID- 18062281
TI  - [The expression and significance of HIF-1alpha and COX-2 in laryngeal squamous
      cell carcinoma].
AB  - OBJECTIVE: To investigate the protein and mRNA expression of HIF-1alpha and COX-2
      in laryngeal squamous carcinoma, and their correlation with clinicopathologic
      parameters. METHOD: The protein and mRNA expression of HIF-1alpha and COX-2 in
      fresh laryngeal squamous carcinoma tissues and adjacent normal tissues from 76
      patients were examined by immunohistochemistry and reverse transcription
      polymerase chain reaction. RESULT: 1) The protein positive expression rate of HIF
      1alpha and COX-2 in tumor samples were significantly higher than that in normal
      tissues (P < 0.05); The protein positive expression rate of HIF-1alpha were
      higher in moderately and poorly differentiated tumors than in well differentiated
      tumors (P < 0.05); While the protein positive expression rate of COX-2 were not
      associated with T stage (P > 0.05); 2) The mRNA positive expression rate of HIF
      1alpha and COX-2 were 67.11% and 75.00% respectively, their expression were
      significantly higher in tumors than that in normal tissues (P < 0.05). The mRNA
      expression of COX-2 were not detected in normal tissues. The mRNA positive
      expression rate of HIF-1alpha were associated with T stage, but were not
      associated with differentiated clinicopathologic stage. 3) The protein positive
      expression rate of HIF-1alpha were associated with that of COX-2. CONCLUSION: HIF
      1alpha and COX-2 could up regulate each other to promote the development and
      metastasis of laryngeal squamous carcinoma.

PMID- 18062282
TI  - [The expressions and significance of CK2 in normal laryngeal mucosa, laryngeal
      precancerosis and laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the expression of protein kinase CK2 and its
      relationship with the development, progress, invasion and metastasis of squamous
      cell carcinoma of larynx (LSCC). METHOD: Immunohistochemical SP staining method
      was used to assess the expression of CK2 in 18 cases of normal laryngeal mucosa,
      14 cases of polyp of vocal cord, 11 cases of larynx papilloma and 50 cases of
      LSCC patients. And RT-PCR was used to detect the expression of CK2alpha mRNA and
      CK2beta mRNA in 50 cases of LSCG patients. The relationship between CK2alpha and
      CK2p was evaluated. RESULT: The positive expression rate of CK2alpha and CK2beta
      in normal laryngeal mucosa, polyp of vocal cord and tissues close to carcinoma by
      1.0 cm, nonmetastatic lymph nodes were lower than that in tissues close to
      carcinoma by 0.5 cm and laryngeal papilloma. The positive expression rate of
      CK2alpha and CK2beta in laryngeal carcinoma and metastatic lymph nodes were the
      highest among the groups. The expression rate of CK2alpha and CK2beta in tissues
      of laryngeal carcinoma and metastatic lymph nodes of neck was significantly
      higher than that of laryngeal papilloma and tissues close to carcinoma by 0.5 cm
      (P < 0.05). In the group of LSCC, the expression of CK2alpha in G2 and in G3 was
      significantly higher than that in G1 (P < 0.05). While the age of the patients,
      TNM stage and lymphatic metastasis didn't change in the expression of CK2alpha
      obviously. The expression of CK2beta correlates to the differentiation grading
      and lymphatic metastasis in LSCC patients, but not to the age and TNM stage. The
      result from RT-PCR was highly consistent with that from immunohistochemical SP
      staining. There was a positive correlation between the expression of CK2alpha in
      LSCC patients and that of CK2beta. CONCLUSION: The over expression of protein
      kinase CK2 may be an accelerator to the formation and development of LSCC.
      Protein kinase CK2 may be one of the predictors for the malignant grade of LSCC.
      To inhibit the over expression might be new therapeutic methods for LSCC.

PMID- 18062283
TI  - [Clinical observation of treating allergic rhinitis with focused ultrasound under
      nasal endoscope].
AB  - OBJECTIVE: To observe the short-term therapeutic effect of focused ultrasound in
      treating allergic rhinitis under nasal endoscope. METHOD: One hundred and
      seventeen patients with allergic rhinitis were treated by the CZB ultrasound
      therapeutic system which was developed and produced by Chongqing Haifu (HIFU)
      Technology Co. Ltd., Chongqing China. It was used to scan inferior nasal concha
      and the anterosuperior part of nasal septum under nasal endoscopy. The
      therapeutic effect was evaluated by clinical symptoms controlled counting-scores,
      according to the Chinese Lan zhou principle of treatment and recommendation
      program for allergic rhinitis. RESULT: The excellent effective rate was 44/117
      cases (37.6%), effective rate was 49/117 cases (41.9%), ineffective rate was
      24/117 cases (20.5%), and the total effective rate was 79.5 after 12 months
      follow up. CONCLUSION: The focused ultrasound is convenient, safe, repetitive and
      effective in treating allergic rhinitis under nasal endoscope. The long-term
      therapeutic effect remains to be further studied.

PMID- 18062284
TI  - [The changes and significance of microsatellite loss of heterozygosity in
      laryngeal premalignant lesions and squamous cell carcinoma].
AB  - OBJECTIVE: To evaluate the character and significance of the loss of
      heterozygosity (LOH) on chromosomes 3P, 9P and 17P in laryngeal premalignant and
      malignant lesions. METHOD: Allelic deletions analysis was performed with 6
      polymorphic markers (D3S1234, D9S171, D9S1748, D9S162, INFA and p53) using
      polymerase chain reaction-single sequence length polymorphism-silver staining in
      49 laryngeal premalignant and malignant lesions. RESULT: Allelic loss was seen in
      3.70% of the six markers in patients with simple hyperplasias (HP), 10.81% with
      low grade dysplasia (LGD), 26.03% with high grade dysplasia (HGD) and 38.67% with
      laryngeal squamous cell carcinoma (LSCC). Significant differences was found
      between allelic loss and clinical pathological grades (X2 = 17.686, P < 0.01).
      The rate of LOH increased remarkably with the lesions progressed from HP to LSCC.
      D9S171showed the highest incidence of LOH (35.00%) on the six markers.
      CONCLUSION: Microsatellite DNA LOHs occur in early stage of laryngeal
      carcinogenesis. Microsatellite markers may be useful in the early diagnosis for
      laryngeal premalignant lesions.

PMID- 18062285
TI  - [The expression of MMP-2, E-cadherin in supraglottic carcinoma and their
      relationship with cervical lymph node metastasis].
AB  - OBJECTIVE: To study the expressions of matrix metalloproteinase-2 (MMP-2) and E
      cadherin in laryngeal carcinoma and their relationship with cervical lymph node
      metastasis. METHOD: The expression of MMP-2 and E-cadherin in 10 cases of normal
      laryngeal mucosa and 48 cases of supraglottic carcinoma were detected by
      immunohistochemistry. RESULT: The expression of MMP-2 in supraglottic carcinoma
      was significantly higher than that in normal laryngeal mucosa. The expression of
      MMP-2 in metastatic lymph nodes was significantly higher than that in
      nonmetastatic lymph nodes (P < 0.05). The expression of E-cadherin was
      significantly lower in supraglottic carcinoma than that in normal laryngeal
      mucosa. The expression of E-cadherin was significantly lower in metastatic lymph
      nodes than that in nonmetastatic lymph nodes (P < 0.05). There is a negative
      correlation between the expression of MMP-2 and E-cadherin (r = -0.41).
      Predicting the lymph node metastasis of laryngeal carcinoma with the index of MMP
      2(+), E-cadherin(-) and MMP-2(+), E-cadherin(-). MMP-2(+) has the highest
      sensitivity, but the lowest specificity and positive predictive value. MMP-2(+),
      E-cadherin(-) has the highest specificity and positive predictive value, but the
      lowest sensitivity. CONCLUSION: Expression of MMP-2 and E-cadherin can be used as
      a marker to predict lymph node metastasis of supraglottic carcinoma. Combined the
      detection of MMP-2 and E-cadherin can boost the accuracy of prediction of lymph
      node metastasis in supraglottic carcinoma and provide efficient assistance for
      resecting supraglottic carcinoma.

PMID- 18062286
TI  - [Reconstruction of the defect of cervical trachea with the sternocleidomastoid
      myoperiosteal flap].
AB  - OBJECTIVE: To study application of sternocleidomastoid myoperiosteal flap to
      reconstruction of the defect of cervical trachea. METHOD: Thirteen hospitalized
      patients with malignant neoplasm invading cervical trachea and primary tracheal
      carcinoma were analyzed retrospectively, the sternocleidomastoid myoperiosteal
      flap was applied to repair the defect of tracheal wall after resection of the
      neoplasm. RESULT: Among 10 tracheotomy patients, 9 cases were decannulated from 1
      month to 5 months. One case needs cannulation because of tracheal stenosis. Three
      patients with no tracheotomy had no dyspnea after operation. CONCLUSION: The
      sternocleidomastoid myoperiosteal flap is an ideal transplant for cervical
      tracheal reconstruction.

PMID- 18062287
TI  - [Treatment of specific foreign bodies in tracheobronchial].
AB  - OBJECTIVE: To improve effectiveness of diagnosis and therapy in patients with
      tracheobronchial specific foreign body. METHOD: Fourty-six cases with specific
      foreign bodies in the trachea and bronchi, admitted from March 1998 to June 2006,
      were analyzed retrospectively. RESULT: Forty-one of 46 the specific foreign
      bodies were successfully removed through bronchoscopy. Three cases were removed
      by chest surgery. Two cases were died. CONCLUSION: Suitable surgical instrument
      should be well selected and the best operation should be applied according to
      different conditions of the foreign bodies. Rigid bronchoscopy for removal of
      specific foreign bodies under general anesthesia is a main measure presently.

PMID- 18062288
TI  - [Application of pectoralis major flap to reconstruction of massive defects after
      head and neck tumor excision].
AB  - OBJECTIVE: To discuss the effectiveness and advantage of application of
      pectoralis major flap in the reconstruction of massive defects after head and
      neck tumor excision. METHOD: Thirteen patients with head and neck carcinoma
      underwent tumor excision, and the massive defects were fixed by pectoralis major
      myocutaneous flap. Ten patients with recurrent laryngeal carcinoma and 2 with
      hypopharyngeal carcinoma and 1 with thyroid carcinoma were included. RESULT:
      Eleven cases healed well, 1 case appearance fistula of parotid gland, 1 case was
      lost to follow-up. CONCLUSION: Pectoralis major myocutaneous flap with adequate
      vascularization, enough tissue and ideal healing ability cab be used to
      reconstruct massive defects. And so it can play an important role in providing a
      better life expectancy and can radically cure or relieve the complaint.

PMID- 18062289
TI  - [The building of multiple drug resistant human laryngeal cancer cell line and its
      characteristics].
AB  - OBJECTIVE: To build the multiple drug resistant human laryngeal cancer cell line
      and investigate its characteristics. METHOD: Human laryngeal cancer cells were
      exposed in stepwise escalating concentration of Taxol until the resistant cell
      line was developed. The IC50 and the resistance folds of multidrug resistance
      were detected by an ATP assay. The differences of cell cycle distribution,
      apoptosis, and Rhodamine accumulation between Hep-2 and Hep-2T cells were studied
      through flow cytometry. The MDR1 and MRP1 gene were detected through realtime
      quantitative RT-PCR, and the corresponding protein was detected through western
      blotting. RESULT: A multidrug resistance cell line-Hep-2T induced by Taxol was
      effectively developed, whose drug resistance was 104 times that of Hep-2 cells.
      Doxorubicin, Gemcitabine, 5-Fu, Cisplatin all increased the drug resistance by
      46.78, 1.95, 2.50, 1.05 folds. The cell cycle distribution altered. The apoptosis
      of Hep-2 cells was quite greater than that of Hep-2T cells (45.32% vs 4.26%, P <
      0.01, flow cytometry), (54.47 +/- 48.95 vs 9.84 +/- 12.53 P < 0.01, hoechst
      staining) after Hep-2 and Hep-2T exposed to Taxol at IC50 to Hep-2. The copy
      ratio of MDR1/GAPDH mRNA of Hep-2T was 64.2 +/- 36.7 times that of Hep-2 (P <
      0.05), while MRP1/GAPDH of Hep-2T was only 1.20 +/- 0.09 folds more than that of
      Hep-2 (P < 0.05). The proteins of MDR1/P-gp were greatly over expressed in Hep-2T
      cells compared with Hep-2 cells (P < 0.01) whose was in the same trend (P <
      0.05), while the elevated expression of MRP1 was lower than that of MDR1/P-gp.
      CONCLUSION: When considering the possible methods to reverse MDR of SCCHN, more
      emphasis should be laid on MDR1/P-gp, and when combining this with chemotherapy
      the non-P-gp substrate chemotherapeutic agents should be considered. At the same
      time, more attention should be paid to the changes of cell cycle distribution
      during the drug selection.

PMID- 18062290
TI  - [Clinical trial of treatment of laryngeal cancer by recombinant adenovirus p53
      combined with chemotherapy].
AB  - OBJECTIVE: To evaluate the effectiveness of recombinant adenovirus p53 injection
      (rAd2p53) combined with cisplatin plus 5-fluorouracil regimen in treating
      laryngeal carcinoma. METHOD: Tumour animal models were established in the back of
      mice with Hep-2 cell line. Recombinant adenovirus p53 injection (rAd2p53) were
      transduced to tumor-bearing mouse by direct intratumoral injection combine with
      cisplatin plus 5-fluorouracil ivgtt. The control group 1 was given recombinant
      adenovirus p53 injection (rAd2p53) simplex. The control group 2 was administered
      with cisplatin plus 5-fluorouracil ivgtt simplex. Then compare the diameters of
      pro-treatment with that of post-treatment and test group with controls. RESULT:
      Tumor growth was significantly inhibited following combined rAd2p53 gene therapy
      with cisplatin plus 5-fluorouracil chemotherapy compared to single rAd2p53 gene
      therapy and cisplatin plus 5-fluorouracil chemotherapy controls. CONCLUSION:
      Local injection of rAd2p53 combined with cisplatin plus 5-fluorouracil
      chemotherapy is a promising treatment to laryngeal cancer.

PMID- 18062291
TI  - [Potential impact of seasonal temperature increase pattern on the succession of
      coniferous-broadleaved Korean pine mixed forest in Xiaoxing'an Mountain].
AB  - With LINKAGES model, a simulation prediction was made on the future succession
      process of coniferous-broadleaved Korean pine mixed forest in Xiaoxing'an
      Mountain under different seasonal temperature increase patterns. The future
      getting-warmer climate was assumed as a 5 degrees C increase of monthly mean
      temperature and an unobvious change of precipitation. Three climate change
      patterns were designed, i.e., temperature increasing range was greater in winter
      than in summer, the same in the two seasons, and greater in summer than in
      winter. The simulation results indicated that when the temperature increasing
      range was greater in winter than in summer, the succession of the present stand
      in Xiaoxing'an Mountain was relatively least affected by temperature increase,
      and the tree species composition still remained a relatively stable coniferous
      broadleaved forest state. On the contrary, when the temperature increasing range
      was greater in summer than in winter, the succession of present stand was most
      significantly affected by temperature increase, and the tree species degenerated
      fastest. It could be concluded that there was a close relationship between the
      succession of coniferous-broadleaved Korean pine mixed forest in Xiaoxing'an
      Mountain and the future climate change patterns. The maximum temperature could be
      the key factor determining the viability of the present tree species.

PMID- 18062292
TI  - [Spatial heterogeneity of photosynthetic characteristics of Castanopsis fargesii
      canopy].
AB  - The vertical and horizontal differences in the energy transmission,
      photosynthetically active radiation, and micrometeorological characteristics of
      forest canopy can lead to a considerable heterogeneity, which should be analyzed
      when estimating forest primary productivity. With Castanopsis fargesii, the
      dominant species in the subtropical evergreen broad-leaved forest in Tiantong
      National Forest Park of Zhejiang Province as test object, this paper studied the
      vertical and horizontal variations of photosynthetic characteristics of its
      canopy. Vertically, the photosynthetic indices such as maximum photosynthetic
      rate (Amax), light saturation point (LSP), and carboxylation efficiency (CCE) of
      north-facing leaves in the canopy all declined in the sequence of top canopy >
      mid-canopy > bottom canopy. The mean values of light compensation point (LCP),
      respiration in light (Rd), and Amax from top canopy to bottom canopy reduced by
      19.4% , 18.1% and 37.1% , respectively. The LSP and CCE of south-facing leaves
      followed the pattern of top canopy > bottom canopy > mid-canopy. These two
      indices decreased by 12.3% in bottom canopy and 71.4% in mid-canopy, compared
      with those in top canopy. The apparent quantum yield (AQY) of leaves followed the
      sequence of bottom canopy > top canopy > mid-canopy, being 1.1 and 1.3 times
      higher at bottom canopy than at top- and mid-canopy, respectively. Horizontally,
      the Amax, LSP and CCE of south-facing leaves at top- and bottom canopy were 0.9%
      31.5% higher than those of north-facing leaves. In mid-canopy however, the values
      of test six indices of north-facing leaves were 9.6%-63.2% higher than those of
      south-facing leaves. It was suggested that in order to estimate and model forest
      primary productivity accurately, the vertical and horizontal heterogeneity of
      photosynthetic characteristics of forest canopy should be analyzed.

PMID- 18062293
TI  - [Dynamics of soil water under Eucommia ulmodes plantation in hilly red soil
      region of southern China].
AB  - By using time domain reflectometry (TDR), a fixed-position monitoring research on
      the dynamics of soil water under Eucommia ulmoides plantation was conducted in a
      hilly red soil region of southern China. The results showed that there was a
      significant difference in the soil water storage among different months, and the
      dynamics of soil water could be divided into the phases of reduction, increase,
      and more reduction. Soil water varied significantly in its vertical distribution,
      and the variation pattern also differed with seasons. The vertical distribution
      of soil water could be divided into two phases, i.e., accumulation and depletion
      based on the seasonal variation of soil water, or rainy season and dry season
      based on the monthly variation of rainfall. Soil water was correlated
      significantly (P < 0.05) with relative humidity (RH), air temperature (t), vapor
      pressure deficit (VPD) and rainfall (R), and regulated by these meteorological
      factors synthetically, among which, rainfall was the most important factor,
      followed by air temperature. The soil water loss rate after rain had a
      significant hyperbolic relationship with durative droughty days, while soil water
      storage had a significant linear negative relationship with this duration (P <
      0.05). With the extension of drought duration after rain, soil water loss tended
      to vary gently with increasing soil depth.

PMID- 18062294
TI  - [Responses of Chinese pine tree ring in Shenyang suburb (Fu Mausoleum) to global
      temperature fluctuation].
AB  - In this paper, the correlations between the variations of Chinese pine (Pinus
      tabulaeformis Carr.) tree ring width in Shenyang suburb (Fu Mausoleum) and the
      local temperature variables, Global Surface Air Temperature Anomaly (GSATA) from
      1880 to 2004, Global Land-Ocean Temperature (GLOTI) from 1880 to 2004 and North
      Hemisphere Temperature Anomaly (NHTA) from 1880 to 2004 were studied. Some close
      correlations were detected, and the local temperature variables, GSATA, GLOTI and
      NHTA had some similar influences on the Chinese pine tree ring width. The air
      temperature in last winter (December and January) and in spring (April and May)
      affected the growth of Chinese pine significantly (P < 0.05). There existed a 3-8
      year periodicity of the variation of Chinese pine tree ring width and the GSATA,
      GLOTI and NHTA, and the 19.3-year and 23.2-year quasi-periodicity of the
      variation of Chinese pine tree ring width corresponded with the 20.8-year quasi
      periodicity of GSATA, GLOTI and NHTA. This study suggested that the Chinese pine
      tree ring width in Shenyang Fu Mausoleum had positive correlations with global
      scale temperature fluctuation, and the temperature increase in the past had a
      positive effect on the Chinese pine growth.

PMID- 18062295
TI  - [Species composition, distribution and phenological characters of pollen
      allergenic plants in Beijing urban area].
AB  - In order to know the species composition, distribution pattern, and phenological
      characteristics of pollen-allergenic plants in Beijing urban area, an
      investigation was made, combined with literature survey and experts interviews.
      The results showed that within the fifth ring of Beijing, there were 99 pollen
      allergenic plant species belonging to 32 genera and 19 families, among which, 52
      species were native plants, accounting for 52.5% of the total, 26 species were
      introduced from other regions of China, occupying 26.3% of the total, and 21
      species were introduced from foreign countries, being 21.2% of the total. The 32
      genera of pollen-allergenic plants in Beijing urban area were mainly North
      Temperate elements, occupying 40.6% , followed by Cosmopolitan and Pantropic
      elements. In all functional sections of Beijing urban area, the pollen-allergenic
      plants were most diversified in urban parks, and had the highest proportion in
      street tree species. The coverage of herbs with strong pollen allergy was in the
      order of waste lands > gym centers and institution yards > greenbelts > parks >
      residential areas > squares. The blooming period of pollen-allergenic arbors in
      Beijing urban area was concentrated in March and April, while that of pollen
      allergenic herbs was from July to September.

PMID- 18062296
TI  - [Effects of rice-duck farming system on physiological characters of rice].
AB  - A field experiment with four treatments of rice-duck farming was conducted in the
      Zengcheng Teaching and Research Base of South China Agricultural University to
      further understand the effects of this farming system on the physiological
      characters of rice. The results showed that rice-duck farming could decrease the
      plasma membrane permeability and the malondialdehyde and proline contents of rice
      leaves, but increase their soluble sugar content and superoxide dismutase,
      peroxidase and catalase activities, indicating that this farming system had
      positive effects to the improvement of rice plant resistance and the postponement
      of leaf aging, being of significance on the rice growth and development.

PMID- 18062297
TI  - [Dynamic principle of ecosystem restoration based on plant diversity].
AB  - The dynamics of ecosystem restoration is an important issue in ecology. Based on
      the theories of island biogeography, plant community succession, biodiversity
      sustaining mechanism and ecosystem function, a dynamic model of ecosystem
      restoration was deduced, and verified by the observation data on semi-humid
      evergreen broadleaved forest at its secondary succession phase. The dynamic
      principle was discussed based on the analysis of the nature of the dynamic model.
      It was indicated that the dynamic process of ecosystem restoration was controlled
      by the integrative effect of ecosystem restoration force F1, disturbance force F2
      and environmental resistance F3. The change rate of plant diversity restoration
      was in inverse proportion to plant species richness, and in direct proportion to
      the total driving force of ecosystem restoration F. F1 and F3 were the functions
      of initial species richness s0 and environmental resources of restoring
      ecosystem, while F2 was the function of disturbance intensity and species
      richness. When the ecosystem was under negative disturbance, plant species
      richness was always lower than the highest species richness sm. The smaller the
      s0, the stronger logistic the ecosystem restoration process would be.
      Mathematical models were established to calculate F1, F2 and F3, and to estimate
      the effects of plant diversity and disturbance on ecosystem restoration. It was
      suggested that the increase of plant species richness could enhance ecosystem
      restoration potential, and promote ecosystem stability.

PMID- 18062298
TI  - [Dynamics and influence width of dry valley landscape boundary in upper reaches
      of Minjiang River].
AB  - Based on RS and GIS techniques, the distribution extent of the dry valley in
      upper reaches of Minjiang River was determined, with the dynamics and influence
      width of its landscape boundary analyzed. The results indicated that the dry
      valley had a gradually expanded distribution, and the total length of its
      boundary was increased. The boundary complexity increased from 1974 to 1995 but
      decreased from 1995 to 2000, and the upper boundary of the dry valley ascended
      rapidly along mountain slope. The uppermost elevation of the dry valley boundary
      was 3128 m in 1974, 3167 m in 1995, and 3181 m in 2000. In the last 26 years, the
      upper boundary of the dry valley ascended 53 m in total, being about 2 m per
      year. The influence width of the dry valley boundary was 800 m, which could be
      regarded as a buffer zone to disturbances. The area between 800-1200 m from the
      dry valley boundary to exterior was a transition zone intensely influenced by the
      dry valley and its surrounding landscape, which should be addressed in the
      restoration of the dry valley.

PMID- 18062299
TI  - [A modified method of ecological footprint and its application].
AB  - The Wackernagel's method of ecological footprint assumes that arable lands are
      cropped only once a year in a country or a region, which does not accord with the
      conception of ecological footprint referring to the area of productive land. In
      this paper, the method of cropland footprint was modified by regulating with
      multi-cropping index, and the ecological footprint calculated with the new method
      was for the area of cropland but not that of multi-cropping. The ecological
      economic systems in Binhai and Funing counties of Jiangsu Province from 1995 to
      2003 were analyzed by the modified method, and the results showed that when
      calculated with conventional Wackernagel's method, the ecological footprints of
      Binhai and Funing were from 1.79 hm2 to 2.22 hm2 and from 1.38 hm2 to 2.81 hm2,
      and the percentages of cropland ecological footprint in total ecological
      footprints decreased from 42.65% to 38.81% and from 45.73% to 38.85%,
      respectively, while calculated with the modified method, the ecological
      footprints and the percentage of cropland ecological footprint in total
      ecological footprints were from 1.43 hm2 to 1.88 hm2 and from 1.12 hm2 to 2.43
      hm2, and decreased from 28.45% to 22.89% and from 32.94% to 29.42%, respectively.
      It was indicated that the ecological footprint calculated with the new method was
      for the area of cropland, which more accorded with the eco-capacity and changed
      the size and composition of ecological footprints, being able to reflect the use
      of natural resources more precisely.

PMID- 18062300
TI  - [Catchment scale risk assessment and critical source area identification of
      agricultural phosphorus loss].
AB  - Agricultural non-point source phosphorus pollution is a severe problem for rural
      water bodies in China, but hard to control directly because of its special
      characteristics. In this paper, an approach on the catchment scale risk
      assessment and critical source area identification of agricultural phosphorus
      loss in northern China was made, based on the catchment scale phosphorus ranking
      scheme and the method proposed by Gburek et al. Eight factors were selected and
      weighed in the modified catchment scale phosphorus ranking scheme, and the
      phosphorus loss risk rating of each factor was adjusted based on the current
      professional standards and the actual circumstances in China. The areas with '
      high' risk rating of phosphorus loss in definite catchment were the critical
      source areas for non-point source phosphorous pollution control in that catment.
      The availability of obtained data and the quantification of the assessment were
      taken into account in the new scheme, and GIS technique and geostatistics were
      used for confirming the factors. Therefore, the new scheme had definite
      operability and practicability.

PMID- 18062301
TI  - [Fractal characteristics of soil particles in surface layer of black soil].
AB  - Based on the second national soil survey of China, the fractal dimension of soil
      particles in the surface layers of 36 typical profiles of black soil was
      calculated. The results showed that the fractal dimension was 2.5831-2.8230,
      being increased with decreasing diameter of soil texture, but the variability was
      inconspicuous. The fractal dimension was negatively correlated with the contents
      of sand (2-0.02 mm) and silt (0.02-0.002 mm) (P < 0.05), but positively
      correlated with clay (< 0.002 mm) content (P < 0.01). No significant correlations
      were observed between soil particle fractal dimension and soil organic matter,
      total nitrogen, total phosphorus, total potassium, and pH. The fractal dimension
      of soil particles could be used as a comprehensive and quantitative index in
      evaluating the degradation degree of black soil.

PMID- 18062302
TI  - [Estimation of CO2 and N2O emissions from farmland soils in Hebei Province in
      Huang-Huai-Hai Plain].
AB  - Taking Hebei Province in Huang-Huai-Hai Plain as a study case, the DNDC model was
      tested with field observation data, and used to estimate the farmlands CO2 and
      N2O emissions. The results showed that the simulated results could better reflect
      the characters of soil CO2 and N2O emissions, and the total CO2 and N2O emissions
      from the farmland soils in 111 counties of Hebei Province in 2003 were estimated
      to be 3.758 x 10(6) t C and 40.345 x 10(6) kg N, respectively. Winter wheat/
      summer maize rotation fields contributed about 40% of the CO2 and N2O emissions,
      and thus, the mitigation of farmland soil CO2 and N2O emissions should be focused
      on the high CO2 and N2O emission counties, especially on the winter wheat/summer
      maize rotation fields in these regions. It could be unnecessary or non-effective
      to mitigate the CO2 and N2O emissions at large scale.

PMID- 18062303
TI  - [Sawfly diversity along an altitude gradient in Mao'er Mountain of Guangxi].
AB  - The sawfly diversity was investigated at seven sampling sites along an altitude
      gradient in the Mao'er Mountain National Nature Reserve of Guangxi in spring. A
      total of 803 sawfly specimen belonging to 121 species, 58 genera and 3 families
      were collected, and the dominant and widespread species were Claremontia
      sinobirmana Malaise and Nesoselandria southa Wei. The maximum values of the
      species richness index, Simpson index and Shannon-Wiener index of sawfly
      communities occurred at the altitude of 1000-1500 m, being 12.293, 0.971 and
      3.830, respectively, while the dominance index was the highest at high altitude.
      The sawfly species at the seven sites were divided into two groups, i.e., high
      altitude group ( > 2000 m) and other altitude group ( <2000 m). Precipitation and
      vegetation type were the main factors affecting the sawfly diversity.

PMID- 18062304
TI  - [Evaluation method and index system of eco-city development: a case study in
      Dafeng City of Jiangsu Province, China].
AB  - City is a kind of social-economic-natural complex ecosystem. How to realize the
      urban sustainable development is one of the important issues in the world. Eco
      city is one of the ideal patterns for urban sustainable development, while the
      evaluation method and related indices of eco-city development are the main basis
      in measuring the effect of urban ecological planning, construction, and
      management. Taking the Dafeng City of Jiangsu Province as a case, the eco-city
      index system consisting of 58 indices of 4 categories including economic
      development, ecological construction, environment protection and social progress
      was established, and the construction effect was evaluated at different urban
      development phases by using Full Permutation Polygon Synthesis Illustration
      method. The results indicated that in 2004, the comprehensive index of Dafeng eco
      city was 0.24, and the sustainable development ability was belonged to class IV,
      i.e., be worse, but in 2010, 2015 and 2020, it would reach to 0.45, 0.66 and
      0.85, and the sustainable development ability would belong to class III, II and
      I, i.e., be moderate, better and excellent, respectively. This research could be
      a reference for decision-making of eco-city development.

PMID- 18062305
TI  - [Application of inverse distance weighted interpolation method in contaminated
      site assessment].
AB  - There are many difficulties in ascertaining the area that needs to be remedied in
      contaminated site. This paper integrated the experts' judgments with grids as the
      sampling strategy in an abandoned pesticide plant in northern China, and applied
      a geostatistical method, inverse distance weighted interpolation (IDW), to
      simulate the pollutants- and risk spatial distribution. Based on soil
      environmental benchmark, two scenarios were designed for ascertaining the
      polluted area. The results showed that the area needed to be remedied and
      determined by IDW was somewhat larger, according to the national environmental
      2nd standard for agricultural soils, but the area and cost needed for remedy were
      smaller and more economic and reasonable, based on the health risk threshold
      level and IDW method. A combination of IDW and health risk assessment in
      ascertaining polluted area would be a new way for site assessment and soil
      remediation in the future.

PMID- 18062306
TI  - [Relationships between aboveground biomass and environmental factors along an
      altitude gradient of alpine grassland].
AB  - In order to analyze the relationships between aboveground biomass and
      environmental factors along an altitude gradient of Bayanbulak alpine grassland
      on the southern slope of Tianshan Mountain, nine plots were selected, with each
      at 100 m interval of altitude. The results showed that Stipa purpurea and Festuca
      ovina communities distributed at the altitude from 2460 to 2760 m, and the
      aboveground biomass were 52.2-75.9 g x m(-2). Kobresia capillifolia + S. purpurea
      communities distributed at altitude 2860 m, and the aboveground biomass was 53.2
      g x m(-2). K. capillifolia, Aichemilla tianschanica and Carex stenocarpa
      distributed at the altitude from 2860 to 3260 m, and the aboveground biomass was
      62.1-107.4 g x m(-2). The mean relative humidity in July and August had greater
      effects on the aboveground biomass. Altitude had a negative correlation with the
      aboveground biomass of gramineous functional group, but a positive correlation
      with that of sedge functional group. The mean air temperature in July and August
      was the key factor affecting the aboveground biomass of gramineous and sedge
      functional groups, and the stepwise regression equations were Y = 13.467X -
      97.284 and Y = 171.699 - 15.331X, respectively (X represented mean air
      temperature, and Y represented aboveground biomass). Altitude was negatively
      correlated with mean air temperature and soil pH value (P < 0.01), and positively
      correlated with mean relative humidity (P < 0.01) and soil available nitrogen and
      water content (P < 0.05).

PMID- 18062307
TI  - [Effects of Fargesia denudata density on its litterfall production, nutrient
      return, and nutrient use efficiency].
AB  - A two-year study on the effects of three densities (D1, 80 +/- 5 stems x m(-2);
      D2, 140 +/- 8 stems x m(-2); and D3, 220 +/- 11 stems x m(-2)) of Fargesia
      denudate in a F. denudata--Picea purpurea natural forest on the F. denudate
      litterfall production, nutrient return, and nutrient use efficiency showed that
      at the densities of D1, D2 and D3, the annual litterfall production was 793.2,
      1135.7 and 1458.5 kg x hm(-2), carbon return was 370.7, 516.2 and 671.5 kg x hm(
      2), and the total return of N, P, K, Ca and Mg was 16.3, 22.9 and 29.3 kg x hm(
      2), respectively. Ca had the highest return (45%-48% of the total), followed by N
      (24%-29%), and the lowest were P and Mg (3%-5%), with the sequence of Ca > N > K
      > Mg and P. The peaks of litterfall production and nutrients return at the three
      densities were appeared in October (by the end of F. denudate growth season), and
      another peak at D3 was observed in August. There were no significant differences
      in the re-allocation of N and K in F. denudate leaves at the three densities, but
      the P re-allocation and the Ca and Mg accumulation increased with increasing
      density. The litterfall P use efficiency was the highest and increased with
      increasing density, implying that P could be a limiting factor for the growth and
      regeneration of F. denudate.

PMID- 18062308
TI  - [Variation of apple tree canopy-air temperature difference and its relations to
      environment factors].
AB  - By using portable infrared thermometer, the canopy temperature (Tc) of apple tree
      in its main growth season was measured in 2002-2005. Combined with the
      synchronous micro-meteorological data on the canopy, such as net radiation (Rn),
      wind speed (V), air temperature (Ta) and relative humidity (RH), as well as the
      soil water content (SW) at 0-80 cm depth, the variation of apple tree canopy-air
      temperature differential (DeltaT) and its relationships to environmental factor
      were analyzed. The results showed that from bud stage to fruit-developing stage,
      there were several peaks in the diurnal curve of DeltaT, with the maximum at
      12:00-13:00 in fine days, and the absolute value of DeltaT in fine days was
      higher than that in overcast days. Based on data of 2003 and 2004, the DeltaT at
      14:00 was significantly correlated with the RH, V, Rn, SW in fine days, and the
      regression equation was DeltaT = 7.159 - 0.002Rn - 0.061V - 0.7RH - 46.0SW (P <
      0.01, r = 0.825). The partial coefficient for Rn, RH, V and SW was 0.125, -0.078,
      -0.036, -0.874, respectively, and the stepwise regression equation was DeltaT =
      5.317 - 43.1SW (P < 0.01), suggesting that SW was the most important
      environmental factor affecting DeltaT. After validated with the measured data in
      2002 and 2005, it was found that the measured DeltaT was highly accorded with the
      simulated one (r = 0.9083, P < 0.01, n = 40), and thus, it was of possibility to
      use the data of DeltaT at 14:00 in fine days to predict the soil water content in
      apple orchard.

PMID- 18062309
TI  - [Seed flows of restoration succession series communities in alkaline meadow of
      Northeast China Songnen Plain].
AB  - After compared the source seed bank, soil seed bank, and seedling bank of the
      dominant species in four communities of restoration succession series in alkaline
      meadow of Songnen Plain, the model of seed flows was established. At early
      succession stage, the density of dominant source seed bank in Choris virgata
      community arrived its maximal value 446,182 +/- 180,455 seeds x m(-2) being 7.2
      times of that in Puccinellia tenuiflora community at intermediate succession
      stage, 11.4 times of that in P. tenuiflora + Leymus chinensis community at later
      succession stage, and 164.8 times of that in L. chinensis community at climax
      succession stage. The densities of soil seed bank and seedling bank were all the
      maximal in C. virgata community, which were 63,650 +/- 14,541 seeds x m(-2) and
      39,160 +/- 15,192 seedlings x m(-2), while the minimal in L. chinensis community,
      being 14,310 +/- 7,686 seeds x m(-2) and 790 +/- 745 seedlings x m(-2),
      respectively, representing a decreasing trend with the restoration. In the
      seedling banks of all communities in the restoration succession series, C.
      virgata was dominant, with its percentage ranged from 79.8% to 100%. In the seed
      flows, the input from dominant source seed banks to soil seed banks was only 10%
      35%, while the output differed significantly at different succession stages,
      being the highest (62.3%) in C. virgata community and none in P. tenuiflora and
      L. chinensis communities.

PMID- 18062310
TI  - [Land use change in the eastern part of Chongming Island in Shanghai in recent
      two decades].
AB  - Under the support of Geographic Information Systems (GIS) and by using the aerial
      photos of 1982 and 2000, this paper analyzed the land use change in the eastern
      part of Chongming Island in past two decades. The results showed that
      agricultural land, water body, aqua-farm and coastal wetland were the main
      landscape components, and the land area for non-agricultural use was increased.
      The overall land use diversified increasingly. Agricultural land, aqua-farm and
      green land increased by 4050.2, 2566.2 and 901.4 hm2, respectively, while coastal
      wetland decreased by 7491.2 hm2. Aqua-farm was the land-use type with the highest
      annual change rate (54.6%), followed by green land (13.24%), traffic (4.49%),
      coastal wetland (-4.47%) and agricultural land (2.57%). The primary transitions
      of land use types were from coastal wetland to agricultural land, aqua-farm,
      green land and water body, from agricultural land to aqua-farm, residential land
      and green land, and from water body to agricultural land, aqua-farm and coastal
      wetland. Rapid socioeconomic development and government decision-making were the
      driving forces of land use change in the eastern part of Chongming Island.

PMID- 18062311
TI  - [Dynamic changes of land desertification landscape pattern in agriculture and
      pasturage interlaced zone of northern Shaanxi].
AB  - By using the 1986, 1993 and 2003 Landsat TM images and with the help of GIS, the
      dynamic changes of land desertification landscape pattern in agriculture and
      pasturage interlaced zone of northern Shaanxi in 1986-2003 were analyzed. The
      results showed that in the past 17 years, the desertification area in the zone
      decreased by 206,655.2 hm2, with the patches in landscape structure reduced and
      fragmentation abated. Fortunately, the desertification degree decreased
      obviously, and moderate and light desertification took the leading position. From
      1986 to 2003, the spatial centroid of desertification landscape patches expanded
      southwestward and northeastward, giving serious threat to the ecological safety
      of the southeast and northeast loess gully and hilly areas.

PMID- 18062312
TI  - [Effects of host plants on development and fecundity of Brontispa longissima
      (Gestro)].
AB  - With Cocos nucifera, Hyophorbe lagenicaulis, Washingtonia filifera, Roystonea
      regia and Areca catechu as test host plants, this paper studied the effects of
      their un-spread leaves on the development and fecundity of experimental
      population of Brontispa longissima. The results showed that the development
      duration of one generation B. longissima fed on different hosts varied
      significantly, with the longest (72.8 days) on W. filifera and the shortest (39.8
      days) on H. lagenicaulis. The average pupa weight of B. longissima was bigger on
      H. lagenicaulis than on the other four host plants, and the female B. longissima
      had the highest fecundity (157.6 ova) on W. filifera while the lowest one (65.2
      ova) on A. catechu. The longevity of B. longissima adults fed on H. lagenicaulis
      was 207.52 days, being significantly longer than that on the other host plants.
      The trend index of experimental population of B. longissima fed on the five host
      plants was 53.57, 54.98, 48.56, 20.46 and 11.54, respectively.

PMID- 18062313
TI  - [Responses of soil fauna to environment degeneration in the process of wind
      erosion desertification of Hulunbeir steppe].
AB  - To reveal the relationships between soil fauna and soil environmental factors in
      the process of steppe desertification, field survey combined with laboratory
      analysis was made to study the community structure, population density and
      biodiversity of soil fauna, and their relationships with the changes of soil
      organic matter, hydrolysable nitrogen, available phosphorus and moisture contents
      and soil pH at different stages of desertification of Hulunbeir steppe. The soil
      faunal specimens collected belonged to 4 phyla, 6 classes and 12 orders. Nematoda
      was the only dominant group of medium- and small-sized soil fauna, occupying
      94.3% of the total, while Coleoptera and Hemiptera were the dominant groups of
      large-sized soil fauna, with the amount of 79.7%. The group amount, population
      density, diversity, and evenness of soil fauna had an obvious decreasing trend
      with the aggravation of steppe desertification. At serious stage of
      desertification, soil fauna vanished completely. The population density of soil
      fauna in 0-20 cm soil layer had significant linear correlations with soil
      nutrients and moisture contents, soil pH, and litter mass, indicating that soil
      fauna had stronger sensibility to the changes of soil environmental factors in
      the process of wind erosion desertification of Hulunbeir steppe.

PMID- 18062314
TI  - [Effects of crop arrangement patterns on arthropod community structure in
      transgenic bollworm-resistant cotton fields].
AB  - The study on the arthropod community structures in transgenic bollworm-resistant
      cotton (cv. Lumianyan 15) fields with different crop arrangement patterns showed
      that compared with those in mono-cultured cotton plot, there were more species of
      arthropod community and of phytophagous pest and natural enemy sub-communities as
      well as more individuals of neutral arthropods in vegetable-, fruit tree-, and
      peanut-cotton plots. More individuals of phytophagous pests in vegetable- and
      peanut-cotton plots, and natural enemies in vegetable- and fruit tree-cotton
      plots were observed. The arthropod community in peanut- and fruit tree-cotton
      plots had the highest similarity, while that in mono-cultured cotton and
      vegetable-cotton plots had the lowest one. The Renyi diversity index indicated
      that compared with mono-cultured cotton plot, vegetable-cotton plot had lower
      diversities of arthropod community and pest sub-community, while fruit tree- and
      peanut-cotton plots had higher diversities of arthropod community and natural
      enemy sub-community, and of arthropod community and pest sub-community diversity,
      respectively. It was concluded that fruit tree-cotton was a recommendable crop
      arrangement pattern for transgenic bollworm-resistant cotton.

PMID- 18062315
TI  - [Isolation, screening nd characterization of hydrogen-oxidizing bacteria in
      soybean rhizosphere].
AB  - Soil hydrogen-oxidizing bacteria can utilize soil gaseous hydrogen as an energy
      source to assimilate carbon dioxide. In this paper, a gas-cycle incubation system
      (H2 treatment system) which can provide stable H2 flow (41.6-125 micromol x L(
      1)) via H2O electrolysis was developed, and a mineral salt agar medium (MSA) was
      used to separate the hydrogen-oxidizing bacteria in soybean rhizosphere. A total
      of 40 bacterial strains were isolated from the incubation system, and their
      hydrogen uptake was measured. 20 of the strains could utilize hydrogen and grow
      autotrophically, which were preliminarily identified as hydrogen-oxidizing
      bacteria. Their colony form and physiological-biochemical characteristics were
      studied.

PMID- 18062316
TI  - [Species diversity and seasonal change of entomogenous fungi in Langya Mountains
      Nature Reserve].
AB  - 672 specimens of entomogenous fungi belonging to 20 species, 8 genera and 4
      families were collected from 20 sampling quadrates in the Langya Mountains Nature
      Reserve of East Anhui. The dominant species were Beauveria bassiana, Paecilomyces
      farinosus, P. cateinannulatus, B. brongniartii and P. fumosoroseus, and B.
      bassiana was most dominant, with the relative abundance of 73.8%. The
      entomogenous fungi in the Reserve were high in amount but low in diversity. The
      amount of isolates and the abundance of each species were the highest in summer
      and decreased with decreasing air temperature and rainfall, while the Pielou
      evenness changed from relatively low to relatively high. Paecilomyces spp. had a
      less seasonal fluctuation of quantity than Beauveria spp.

PMID- 18062317
TI  - [Impact of heavy metals pollution on the community structure and spatial
      distribution of soil animals].
AB  - By sampling at 8 plots surrounding the coal-mining and coal-ash areas in Huannan
      City of Anhui Province, a total of 3859 individuals of soil macro-, meso-, and
      micro-fauna belonging to 22 groups, 9 classes and 4 phyla were collected. The
      dominant groups were Collembola, Acarina and Nematoda, accounting for 74% of the
      total, and the others were frequent and rare groups. Heavy metals pollution had
      powerful impact on soil animals. The individual numbers and groups of soil
      animals declined with the aggravation of heavy metals pollution from out of the
      dam site to the nearing site of coal-ash area in Luohe Power Plant, and showed an
      abnormal distribution or little change in vertical and disappeared in surface
      layer. The heavy metals pollution resulted in a decline in the diversity index,
      evenness and density-group index, but a rise in the dominance index of soil
      animals.

PMID- 18062318
TI  - [Changes of NO3(-)-N and NH4(+)-N concentrations in sewage sludge before and
      after heavy metals removal by organic acids].
AB  - This paper studied the removal effect of citric acid, oxalic acid and acetic acid
      on cadmium (Cd), lead (Pb), copper (Cu) and zinc (Zn) in sewage sludge, and the
      changes of NO3(-)-N and NH4(+)-N concentrations in extracted liquid and sludge
      before and after treated. The results showed that 0.8 mol x L(-1) of citric acid
      had better effect, which could remove 76.0% of Pb and 92.5% of Zn in the sludge.
      After treated with test organic acids for 24 hours, large amounts of NO3(-)-N and
      NH4(+)-N dissolved in extracted liquid. Compared with the control (distilled
      water), organic acids greatly increased the NH4(+)-N, but decreased the NO3(-)-N
      in extracted liquid. Because of the transformation of other forms nitrogen in the
      process of acid treatment, the NO3(-)-N and NH4(+)-N concentrations in the
      treated sludge were still high. The extracted liquid after the sludge was treated
      with 0.5 mol x L(-1) of oxalic acid contained 2.8 mg x L(-1) of NO3(-)-N and
      888.1 mg x L(-1) of NH4(+)-N but a few of heavy metals, which was able to be
      reused as a liquid fertilizer.

PMID- 18062319
TI  - [Water pollution load in coastal zone of Xiamen: estimation and forecast].
AB  - By the methods of grey prediction and curve regression, the estimation and
      forecast models of water pollution load in coastal zone of Xiamen City, Southeast
      China were established, and validated with the statistic data of the pollution
      load in past decade. The estimation revealed that the industrial wastewater
      discharge per ten thousand RMB production value decreased yearly, while the total
      discharge of main pollutants increased gradually. In the total discharge of point
      source wastewater, about 76% of nitrogen and phosphorus came from domestic
      wastewater. In non-point source pollution loads, nitrogen and phosphorus of
      agricultural source occupied a larger proportion, while those of urban source
      were the least. In 2005, the nitrogen pollution load from different sources was
      in the order of domestic wastewater (DW) > agricultural non-point source (ANPS) >
      industrial wastewater (IW) > tourism wastewater (TW) > urban non-point source
      (UNPS), while phosphorus pollution load was ANPS > DW > IW > TW > UNPS.

PMID- 18062321
TI  - [Investigation and analysis of China residents' environmental conservation
      desire].
AB  - From the viewpoints of country's safety and residents' desire, this paper
      investigated and analyzed the factors affecting China residents' attitudes on
      environmental protection policies, and the implementing results of these polices.
      It was indicated that people have an enhanced consciousness on environmental
      protection, and the relations between this consciousness and economic growth fit
      Kuznets curve, because most of the poor people are living in the suburban or
      remote regions with bad or seriously degraded environment, while the fast
      development of urbanization accelerates the deterioration of urban environment.
      People are more concerned about environment deterioration, and support the
      governments' policies of environmental conservation. The environment policy
      making should put more emphasis on developing economics, strengthening education,
      and improving residents' livelihood.

PMID- 18062320
TI  - [Effects of low dosage pyrene pollution on biochemical characters of earthworm
      (Eisenia fetida) in soil].
AB  - By the method of artificial soil pollution, an exposure experiment with different
      concentrations of pyrene (0, 60, 120, 240, 480, 960 microg x kg(-1)) was
      conducted to determine the cytochrome P450 and MDA contents and the glutathione-S
      transferase (GST), superoxide dismutase (SOD), peroxidase (POD) and catalase
      (CAT) activities in earthworm gut after exposure for 1, 3, 7 and 14 days. The
      results indicated that within the range of test pyrene concentrations, all the
      biochemical indices tested differed in their sensitivity to pyrene toxicity,
      among which, P450 content and GST and SOD activities were most sensitive,
      followed by POD and CAT activities, while MDA content did not show any obvious
      response. Exposure duration had stronger effects than exposure dosage. In
      diagnosing the ecotoxicity of soil pollutant, it could be necessary to use a
      combined multi-time and multi-index diagnostic method to enhance the sensitivity
      and effectiveness of the indices adopted.

PMID- 18062322
TI  - [Effects of Zn on the growth, Cd accumulation and physiological resistance of
      Iris lactea var. chinensis under Cd stress].
AB  - A solution culture experiment was conducted to examine the effects of Zn (1-100
      mg x L(-1)) on the growth, Cd accumulation, and antioxidant enzyme activities of
      Iris lactea var. chinensis under Cd stress (10 mg x L(-1)). The results showed
      that after the addition of Zn, the Cd content changed a little in shoots, but
      increased significantly in roots, with a trend of rising first and dropping then.
      When treated with 1 mg Zn x L(-1), the Cd content in roots was the highest, being
      51.4% higher than the control. When the Zn concentration was higher than 1 mg x
      L(-1), the Cd content in roots decreased to some extent, but was still higher
      than the control. Low concentration (1-10 mg x L(-1)) Zn increased the shoot
      biomass and leaf chlorophyll content, but decreased the malondialdehyde (MDA)
      content. At 10 mg Zn x L(-1), the chlorophyll a and b contents went up to the
      maximum, being 5.21% and 22.27% higher than the control, respectively, while the
      MDA content decreased by 25.46%, indicating that low concentration Zn could
      alleviate Cd damage. With increasing Zn concentration, the alleviation effect of
      Zn on Cd damage decreased gradually. When the Zn concentration was 100 mg x L(
      1), I. lactea var. chinensis was damaged most seriously, with the biomass and
      chlorophyll content reduced and MDA content increased significantly. Within the
      ranges of test Cd and Zn concentrations, the activities of superoxide dismutase
      (SOD) and peroxidase (POD) had an increasing trend, suggesting that SOD and POD
      played an important antioxidant protective role for Cd or Zn-Cd stressed I.
      lactea var. chinensis.

PMID- 18062323
TI  - [Research progress on biology and ecology of Harmonia axyridis Pallas
      (Coleoptera: Coccinellidae)].
AB  - Harmonia axyridis Pallas (Coleoptera: Coccinellidae) with its native in Asia is
      one of the most important predatory ladybird beetles, and used worldwide as a
      biological control agent. This paper summarized the recent decades research
      progress at home and abroad on its life history, reproductive strategies, and
      predatory and cannibalism behaviors, and analysed the prospects of its
      utilization. Based on the review of its artificial reproduction, insecticide
      interaction, and impact as an invasive species, some useful measures were
      suggested to prevent the beetle from its potential risk to ecological banlance.

PMID- 18062324
TI  - [Psychrophilic methanogens and their application in anaerobic wastewater
      treatment].
AB  - Psychrophiic methanogens play a very important role in global carbon cycle, and
      attract more and more research interests. The application of psychrophilic
      methanogens in anaerobic biotreatment process could essentially break through the
      bottle-neck of anaerobic technology at lower temperature, greatly extend the
      application fields of anaerobic technology, and reduce the operational cost of
      wastewater treatment. In this paper, the research progress on psychrophilic
      methanogens was reviewed, with the focus on their culture, isolation,
      physiological and biochemical characters, molecular biological characters, and
      cold-adapted mechanisms. The application prospects of psychrophilic methanogens
      in low-temperature anaerobic bio-treatment technology were also analyzed.

PMID- 18062325
TI  - [Research advances in microbial ecology of biofilter and biotrickling filter for
      waste gases treatment].
AB  - Waste gases biofiltration is an emerging technology, and has played important
      roles in air pollution control. In this paper, the structure of biofilter and
      biotrickling filter and their mechanisms in air pollution removal were
      introduced, with focus on the research advances in the isolation and
      identification of microbes in the filters, correlations between microbial
      abundance, activity and community diversity, influences of operation conditions
      on microbial community, spatiotemporal change patterns of microbial community
      structure during operation, development of biofilm, and biodegrading dynamic
      models. The research perspectives in microbial ecology during biofiltration of
      waste gases were discussed.

PMID- 18062326
TI  - [Effects of enhanced UV-B radiation on the growth of five bryophytes in Changbai
      Mountains].
AB  - Five bryophytes (Rhytidium rugosum, Rhytidiadelphus triquetrus, Hylocomium
      splendens, Hylocomium pyrenaicum, and Polytrichum alpinum) were exposed to 0.2 kJ
      x m(-2) x d(-1) (visible light under native condition, CK), 3.0 kJ x m(-2) x d(
      1) (simulated dose of UV-B irradiance at the tundra in Changbai Mountains, medium
      dose of UV-B irradiance, T1), and 6.0 kJ x m(-2) x d(-1) (high dose of UV-B
      irradiance, T2) to investigate the effects of enhanced UV-B radiation on plant
      height, biomass, and chlorophyll content. The results indicated that medium and
      high UV-B radiations decreased the plant height, biomass, and chlorophyll content
      of R. triquetrus and H. splendens by 32.3%, 62.4%, and 81.3%, and 21.4%, 59.4%,
      and 62.8%, respectively, and the relative growth rates were negative. Enhanced UV
      B radiations had less effect on P. alpinum chlorophyll content but doubled its
      below-ground biomass, and slightly increased the biomass of R. rugosum. P.
      alpinum and R. rugosum had higher tolerance against UV-B radiation, while R.
      triquetrus and H. splendens were more sensitive to UV-B radiation.

PMID- 18062328
TI  - [Effects of EDTA on lead accumulation in Tagetes patula and Salvia spendens].
AB  - Pot experiments were conducted to investigate the effects of EDTA on the Pb
      availability in rhizospheric soil and the Pb accumulation in Tagetes patula and
      Salvia spendens. The results showed that 7 days after applying EDTA (3.0 mmol x
      kg(-1)) into soil, the concentration of ammonium acetate (1 mol x L(-1)) 
      extracted Pb in rhizospheric soil increased significantly (P < 0.01), and the Pb
      content in T. patula and S. spendens leaves reached to 2415.88 and 1083.68 mg x
      kg(-1), being 61.36 and 5.37 times of the control, respectively. The Pb content
      also had a marked increase in T. patula and S. spendens stems, but had a slight
      decrease in their roots.

PMID- 18062329
TI  - [HIV infection: entry and integrase inhibitors].

PMID- 18062327
TI  - [Revaluation of soil heavy metals pollution in Zhangshi irrigation area of
      Shenyang and analysis of Cd forms in soil].
AB  - This paper revaluated the situation of cadmium (Cd) pollution in rice field soils
      of Zhangshi irrigation area in Shenyang. The results indicated that the soil Cd
      pollution of test area was still quite serious. The Cd content in brown rice
      samples ranged from 0.435 to 0.855 mg x kg(-1), which exceeded the national
      criteria for food sanitation in China, and increased by 335%-755% compared with
      that 20 years ago. Brown rice Cd had a significant negative correlation with soil
      pH, and a positive correlation with soil available Cd. The decrease of soil pH
      induced more soil Cd transformed into available Cd which occupied 22.8%-52.0% of
      the total Cd and was easy to be absorbed by rice plant, inducing the Cd in brown
      rice exceeded national criteria. The pollutant Cd could transfer along with
      surface runoff, ground water and flying dust, making the pollution extend
      gradually.

PMID- 18062330
TI  - [Pregabalin--a neuromodulator for the treatment of neuropathic pain, generalized
      anxiety disorders and fibromyalgia syndrome].
AB  - Synthesized in 1990 as an anticonvulsant agent, pregabalin was designed as a
      lipophilic gamma-aminobutyric acid (GABA) analog substituted at the 3'-position
      in order to facilitate diffusion across the blood-brain barrier. It is an
      alpha2delta1 ligand that binds to, and modulates, voltage-gated calcium channels.
      This modulation is characterized by a reduction of the excessive neurotransmitter
      release that is observed in certain neurologic and psychotic disorders.
      Pregabalin has analgetic, anticonvulsant, and anxiolytic activity and has
      demonstrated efficacy in the management of neuropathic pain associated with
      diabetic peripheral neuropathy, postherpetic neuralgia, and as adjuvant therapy
      for adult patients with partial onset seizures. Pregabalin was significantly more
      effective than placebo for the treatment of generalized anxiety disorder as well
      as of fibromyalgia and was well tolerated by most of the patients.

PMID- 18062331
TI  - [Generalized anxiety disorder (GAD)--diagnosis and therapy].
AB  - The GAD is an important psychiatric disorder with high comorbidity and often
      chronic course. The differentiation against depression is not easy. In this
      review evidence based standards of therapy are discussed. The complex etiology
      and pathogenesis give a rationale for an integrative therapeutic approach, but
      this does not necessarily mean a combination of pharmacotherapy and psychotherapy
      for every patient. The pharmacotherapy with SSRI, SNRI, opipramol, buspirone and
      pregabalin allows an effective treatment. The empirical validated behaviour
      therapy is alternatively possible. Both approaches include a respectable number
      of therapy non-responders.

PMID- 18062332
TI  - [Pharmacotherapy of a geriatric patient with Parkinson's disease].
AB  - Geriatric patients are often treated with a variety of drugs. Due to the complex
      pharmacotherapy there is a high potential of drug-related problems such as drug
      drug interactions, adverse effects and medication errors. This article describes
      how the drug therapy of a geriatric patient with Parkinson's disease was
      optimized using SOAP notes.

PMID- 18062333
TI  - [Are AT1 receptor antagonists an alternative to ACE inhibitors in angioedema?].
AB  - History of angioedema is a contraindication for ACE-inhibitors. Angioedema is
      caused by: 1. a decreased degradation of bradykinin, 2. a defect in C 1-esterase
      inhibitor with the increased generation of bradykinin or 3. other trigger
      mechanisms as food, pollen and stress. AT1 receptor antagonists do not inhibit
      the degradation of bradykinin. Thus angioedema is no contraindication for AT1
      receptor antagonists. In patients with an anamnestic angioedema or ACE-induced
      angioedema AT1 receptor antagonists can be given under close monitoring provided
      that there is strong indication for inhibition of the renin-angiotensin system.

PMID- 18062334
TI  - [Protection with influenza vaccine from bird flu?].

PMID- 18062335
TI  - [Raltegravir an integrase inhibitor--a great leap forward within reach].

PMID- 18062336
TI  - [Hantaviruses. Infection numbers increase!].

PMID- 18062337
TI  - [Hepatitis c virus infections. New therapeutic treatments].

PMID- 18062338
TI  - [Diabetes mellitus type 2. Reduced risk with whole grain product?].

PMID- 18062339
TI  - [Diabetes mellitus type 1. Is cognitive function influenced by treatment?].

PMID- 18062340
TI  - [Stroke. Enoxaparin sodium inhibits venous thromboembolism compared to
      unfractionated heparin].

PMID- 18062341
TI  - [HDL infusion in patient with acute coronary syndrome].

PMID- 18062342
TI  - [Chronic obstructive pulmonary disease. No increased survival with combination
      therapy].

PMID- 18062343
TI  - [Greater risk for hip fractures in disordered kidney function].

PMID- 18062344
TI  - [Hepatic iron, iron depletion and response to therapy with peg-Interferon and
      Ribavirin in chronic hepatitis C. Pilot study].
AB  - AIM: To estimate whether pretreatment serum iron levels, the HIC (hepatic iron
      concentration) and the distribution of hepatic iron identify the long-term
      "responders" and "non-responders" to therapy with peg-IFN and RBV, and whether
      the addition of phlebotomy could increase the likelihood of therapeutic response.
      PATIENTS AND METHODS: 45 subjects with chronic hepatitis C were taking peg-IFN
      alpha-2a 180 microg once a week and RBV 1000 mg/die. The "responders" continued
      therapy with peg-IFN plus RBV, while, the "non-responders" were subjected to
      phlebotomy. After two weeks and subsequently every month the patients were
      subjected to blood test and clinical appraisal. RESULTS: Hepatic iron storage
      meaningfully conditions the outcome of therapy with peg-IFN and RBV, its
      reduction by phlebotomy favourably correlates with response to treatment and, at
      last, the semiquantitative histological appraisal would have to be included in
      the pre-treatment work-up of patients with chronic hepatitis C. CONCLUSIONS: The
      study results, even though obtained on a small size of cases, allow to conclude
      that serum corporeal iron evaluation underestimates the real hepatic iron
      concentration; the hepatic iron concentration, in turn, negatively conditions the
      response to therapy with peg-IFN and RBV (by reducing the percentage of the fast
      virological response). Lastly, iron removal by phlebotomy favourably correlates
      with the response to treatment.

PMID- 18062345
TI  - [The new magnetic therapy TAMMEF in the treatment of simple shoulder pain].
AB  - AIMS: Numerous studies have demonstrated the utility of extremely low frequencies
      (ELF) electromagnetic fields in the treatment of pain. Moreover, the effects of
      these fields seems to depend on their respective codes (frequency, intensity,
      waveform). In our study we want to assess the effects of the TAMMEF (Therapeutic
      Application of a Musically Modulated Electromagnetic Field) system, whose field
      is piloted by a musical signal and its parameters (frequency, intensity,
      waveform) are modified in time, randomly varying within the respective ranges, so
      that all possible codes can occur during a single application. PATIENTS AND
      METHODS: Sixty subjects, affected by shoulder periarthritis were enrolled in the
      study and randomly divided into three groups of 20 patients each: A exposed to
      TAMMEF, B exposed to ELF, C exposed to a simulated field. All subjects underwent
      a cycle of 15 daily sessions of 30 minutes each and a clinical examination upon
      enrollment, after 7 days of therapy, at the end of the cycle and at a follow-up
      30 days later. RESULTS: All the patients of groups A and B completed the therapy
      without the appearance of side effects: they presented a significant improvement
      of the subjective pain and the functional limitation, which remained stable at
      the follow-up examination. In group C, there was no improvement of the pain
      symptoms or articular functionality. CONCLUSIONS: This study suggests that the
      TAMMEF system is efficacious in the control of pain symptoms and in the reduction
      of functional limitation in patients with shoulder periarthritis. Moreover, the
      effects of the TAMMEF system cover those produced by the ELF field.

PMID- 18062346
TI  - Twenty-nine year study on circadian distribution of urinary zinc levels of same
      male subjects.
AB  - OBJECTIVES: To examine the circadian distribution and total 24h levels of urinary
      zinc (Zn) in same male subjects over an extended period of time in order to
      ascertain their relationship with aging. MATERIALS AND METHODS: Eight young army
      volunteers served as subjects over a period of 29 years: 1969, 1979, 1988, 1998.
      By 1979 three of them became latent diabetics. Complete physical examination,
      anthropometric measurements and same procedural protocol was followed in each
      study. Samples were collected over 3 hour periods for 24 hours in the middle of
      each month of May. Urine aliquots were analyzed for creatinine, using
      conventional laboratory procedure. Zn was analyzed using Atomic Absorption
      Spectrophotometry in 1969, and 1979 and by Inductively Coupled Plasma, in 1988
      and 1998. RESULTS: Over the course of 29 years the circadian distribution of Zn
      was altered by decrease in amplitude in Zn levels, while the 24h concentrations
      of Zn decreased progressively with increasing age in healthy and diabetic
      subjects: Healthy; 966+/-130 microg at age of 29; 666+/-14 microg at 39; 511+/-80
      microg at 48; and 555+/-71 microg at age of 58y; Diabetics exhibited similar
      trend; 1757+/-60 microg at age 28; 1253+/-40 microg at age 38, 1132+/-31 microg
      at 47, and 1025+/-11 microg at the age of 57. Anthropometric measurements in each
      study period revealed significant increases in diabetic subjects for body weight,
      body surface area, BMI and significant decrease in body heights of both groups.
      CONCLUSIONS: The daily excretion of urinary Zn over the 29 years period decreased
      by 42% in healthy and diabetic subjects. Although there appears to be a lack of a
      reliable index of intracellular Zn status to accurately monitor and control zinc
      deficiency in younger and older populations, the present data suggest that
      depletions of Zn are also evident in healthy aging subjects whose daily diet was
      not deficient in zinc.

PMID- 18062347
TI  - [The incidence of dental caries during childhood. A clinical and epidemiologic
      study in Matera (Southern Italy)].
AB  - AIM: The aim of the present study is to obtain comprehensive epidemiological data
      of the incidence of oral and dental health conditions in an Italian homogeneous
      population of schoolchildren. MATERIALS AND METHODS: The study has been performed
      on schoolchildren born, living and attending the primary school in Matera,
      Basilicata, Southern Italy. Such data have been compared with the alimentary
      habits of the participants to the study, as well as with the social-economic
      family situations and with the social-environmental data. RESULTS: The data show
      a marked difference in the habits of oral hygiene, and in the health status of
      the oral structures also, based on both the sex and the environment of life.
      CONCLUSIONS: Such differences in the prevalence of caries among various urban
      areas and the behavioural habits related to sex and age ratios may be very useful
      findings for future regional prevention programs.

PMID- 18062348
TI  - [Distal hyperplastic polyps as a marker for advanced neoplasm of the proximal
      colon. Our experience].
AB  - BACKGROUND AND AIM: While, several studies indicate that there is an association
      between proximal and distal colorectal adenomas, no agreement seems to be between
      the presence of distal hyperplastic polyps and proximal neoplasia. The aim of
      this study was to investigate, retrospectively, the possible correlation between
      the distal hyperplastic polyps and proximal colorectal neoplasia. MATERIALS AND
      METHODS: In our GI Unit, from 1st February 2006 to 24 November 2006, we performed
      142 polypectomy. Patients were 36 females and 80 males, with a median age of 66
      years [range: 38-87 years]. All of the polpys were resected during colonoscopy
      and sent for histological study. Chi-square test was used for statistical
      analysis. A probability value of P< or =0.05 was considered to be statistically
      significant. RESULTS: Histological study showed the following results: 33
      hyperplastic polyps (8 F, 21 M; median age 63 years), 100 adenomas (26 F, 61 M;
      median age 67 years) and 2 inflammatory polpys (2 F, 0 M; median age 71 years).
      The rectal localization was associated with a significantly higher frequency of
      hyperplastic polyps (63.6% vs 23.5%), OR: 5.688 (95% C.I. 2.445-13.230)
      (p<0.0001). Five hyperplastic polyps of the rectum were associated with 5
      adenomas located 1 in the rectum, 2 in the sigmoid colon, and 1 in the descendens
      colon and 1 in the ascendens colon. While, 5 adenomas were associated with 5
      adenocarcinoma. CONCLUSIONS: Guidelines from the American College of
      Gastroenterology and the American Society of Gastrointestinal Endoscopy do not
      recommend colonoscopy for patients with distal hyperplastic polyps. Also our
      study is in keeping with the data of the literature and it confirmed that rectal
      localization is associated with a higher prevalence of hyperplastic polyps.

PMID- 18062349
TI  - Subtrochanteric femoral fracture in a 26 year old woman affected by beta
      thalassemia major due to minor trauma: analysis of bone modification causing the
      complication.
AB  - Beta-Thalassemia Major (TM), firstly described by Cooley, is and inherited blood
      disorder that leads to anaemia due to an imbalanced globin chain synthesis
      effecting erythroid maturation and red cells survival and requests regular life
      long blood transfusions and iron-chelating therapy. Among all the complications
      and organ diseases, osteopenia and osteoporosis, as progressive diseases are
      getting important cause of morbidity in a population whose longevity is
      increasing. The authors describe a case of a 26-year-old female with Beta
      Thalassemia Major affected by a subtrochanteric fracture of the right femur on
      minor trauma. Cardiovascular, endocrinologic and thrombotic pattern leading to
      bone modifications are reported and Literature reviewed. Fracture was surgically
      treated with anterograde reconstructive intramedullary locked nail (AFN, Synthes)
      with 2 distal screws inserted in a static mode.

PMID- 18062350
TI  - Reduction of intima-media thickness in subjects with asymptomatic carotid
      disease: two cases from the Asymptomatic Carotid Atherosclerosis DIsease
      Manfredonia Study (ACADIM Study).
AB  - The intima-media thickness (IMT) of carotid common arteries (CCA) represents an
      important step of carotid plaque formation and progression, and is a
      characteristic marker of atherosclerosis, one of the most principal determinants
      of coronary artery disease (CAD). Change in IMT is one of the currently used
      markers to evaluate the progression of atherosclerotic process. In particular
      rosuvastatin (ROS) has demonstrated in a large scale controlled study with
      placebo a significant reduction of coronary atherosclerosis. Two subjects with
      normal lipidic profile underwent a carotid ultrasound investigations (CUI) and
      received ROS (10 mg/day). The CUI documented a bilateral IMT of CCDX and CCSX for
      the case A (0.101 cm dx-0.105 cm sx; mean 0.103 cm) and B (0.114 cm dx-0.108 cm
      sx; mean 0.111 cm), in absence of stenosis or occlusion. After 16 treatment-weeks
      with ROS it has found a significant reduction of IMT for both case A (0.081 cm dx
      -0.096 cm sx; mean 0.088 cm) than case B (0.082 cm dx-0.084 cm sx; mean 0.083
      cm). The treatment with ROS has been well tolerated and no adverse effects has
      been reported. ROS represents an efficacious IMT-lowering agent of the statin
      class. The two presented case reports confirm the benefit of ROS in the IMT
      reduction in subjects with normal LDL-C values.

PMID- 18062351
TI  - Organizational models of emergency psychiatric intervention: state of the art.
AB  - Authors outline the differences between medical and psychiatric definition of
      emergency and analyze different organizational models of psychiatric intervention
      in Emergency Room. The historical evolution changed these models, and the
      relation with services for acute and subacute patients in hospital and community
      services. The Italian reform model is compared with the slow
      deinstitutionalization of psychiatry in other countries. Critical points in
      Italian emergency organization after the Psychiatric Reform are pointed out: low
      number of beds for acute patients, difficulties and delays in transfer from
      Emergency Room to GHPW (General Hospital Psychiatric Ward), waiting lists for
      voluntary treatments. To overcome some of these problems, the Authors propose
      that even in hospitals without psychiatric ward, a small unit of short
      psychiatric observation be implemented, for voluntary treatments, before transfer
      to other institutions.

PMID- 18062352
TI  - [Neoadjuvant endocrine therapy for locally advanced breast cancer].
AB  - The use of neoadjuvant chemotherapy in the treatment of locally advanced breast
      cancer is now well established. However, endocrine therapy can be a valid
      alternative to primary chemotherapy in the treatment of hormone-sensitive tumors,
      particularly in post-menopausal women. Tamoxifen (TAM) was initially used in
      older or frail patients who were not candidates for chemotherapy. Response rate
      of 49% to 68% were observed. These encouraging results prompted subsequent
      randomized phase III studies demonstrating the superiority of surgery in
      comparison to TAM as primary treatment. The successful use of aromatase
      inhibitors (AI) in the metastatic and adjuvant setting has encouraged studies
      that compare these agents with tamoxifen in the neoadjuvant setting. In terms of
      response rates, anastrozole and exemestane did not differ from TAM, while
      letrozole was superior. Nevertheless, all the AI were found to be superior to TAM
      as far as breast conserving surgery is concerned. The Americal College of
      Surgeons Oncology Group (ACOSOG) has recently activated a neoadjuvant randomized
      trial comparing anastrozole, letrozole and exemestane in postmenopausal patients
      with estrogen receptor positive tumors. Hopefully, this study will clarify which
      of these agents is more effective as primary endocrine therapy. In the meantime,
      neoadjuvant hormonal treatment should be considered in elderly patients with
      inoperable tumors or tumors not amenable to conservative surgery, with highly
      expressed estrogen receptors and contraindication to chemotherapy.

PMID- 18062353
TI  - The therapy of Sjogren's syndrome: a review.
AB  - The Sjogren's syndrome (SS) is an chronic inflammatory autoimmune disease of the
      exocrine glands as well as of internal apparatus. The therapy of exocrinopathy is
      represented by parasympathomimetic drugs such as pilocarpine and cevimeline. The
      therapy of systemic manifestations, actually is represented by the inhibitors of
      TNF alfa, as well as leflunomide, methotrexate and cyclosporine-A, but the
      results are quite insufficient and disappointed. In order to the involvement of B
      cell function in the pathogenesis of SS, one of the most important option in the
      future should be specific inhibitors of that cells.

PMID- 18062354
TI  - [Therapeutic options for metabolic syndrome in obese patients].
AB  - The metabolic syndrome (MS), a cluster of risk factors, such as obesity,
      hyperglycemia, hypertension and dyslipidemia, contributes to the development of
      cardio-vascular diseases and type 2 diabetes mellitus (DM2). Insulin resistance
      (IR) plays a key role in MS being strongly linked to abdominal visceral fat.
      Treatment for obese patients with MS should aim at improving IR, delaying the
      onset of DM2 and at reducing cardio-vascular risk. Weight loss, first therapeutic
      target, may be obtained through life-style modifications and anti-obesity drugs
      or bariatric surgery, at need. In these patients drug therapy is necessary if
      therapeutic life-style changes are not sufficient. Some drugs have adverse
      metabolic effects, therefore the therapeutic choices must be specific and
      rational. Metformin, Thiazolidinediones and Acarbose are anti-hyperglycemic drugs
      of choice: they reduce the incidence of DM2 and IR (or improve insulin
      sensitivity) and they decrease or stabilize the visceral adipose tissue mass
      (Thiazolidinediones increases subcutaneous fat only). Also Angiotensin II
      receptor blockers and Angiotensin-converting enzyme inhibitors reduce the
      incidence of DM2 and insulin resistance and they are first-line antihypertensive
      drugs in MS. Calcium channel blockers, Alpha-1 antagonists and Alpha-2 agonists
      drugs are metabolically neutral and slight weight gains are related to the hydro
      sodium retention. Beta-blockers and Diuretics, except for Indapamide and Anti
      aldosterone drugs, can reduce insulin sensitivity, impair lipid profile and
      increase DM2 incidence; they are not first-line therapy yet they are necessary in
      selected cases only. Statins, Fibrates and omega-3 Fatty acids are indicated to
      normalize dyslipidemia. Low doses of acetylsalicylic acid are also recommended.

PMID- 18062355
TI  - [Imaging of acute brain inflammatory disease].
AB  - The central nervous system inflammatory disease can be due to any kind of
      infective agent (bacterial viral, fungal and parasitic), but entails also
      multiple sclerosis, a primary demyelinating disease in which the causal agent is
      unknown. MR imaging is, in most often, the procedure of choice, due to her
      multiplanar and multiparametric imaging, and to her better contrast resolution.
      The post-contrast imaging with double dose of gadolinium and late sequences
      enable visualisation of smallest pathologic foci or slightest blood-brain barrier
      alterations, with a sensibility very higher than post-contrast CT scan. In
      addition, RM provide to many functional informations, by means of diffusion,
      perfusion and spectroscopy studies, Bold technique for cortical activation
      studies and Fiber Tracking technique, in order to demonstrate pathologic
      modification earlier than they are evident on morphologic imaging. Functional
      imaging is also employed to monitor response to treatment and damage
      reversibility.

PMID- 18062356
TI  - Discrepancy between parental reports of infants' receptive vocabulary and
      infants' behaviour in a preferential looking task.
AB  - Two experiments are described which explore the relationship between parental
      reports of infants' receptive vocabularies at 1 ; 6 (Experiment 1a) or 1;3, 1;6
      and 1;9 (Experiment 1b) and the comprehension infants demonstrated in a
      preferential looking task. The instrument used was the Oxford CDI, a British
      English adaptation of the MacArthur-Bates CDI (Words & Gestures). Infants were
      shown pairs of images of familiar objects, either both name-known or both name
      unknown according to their parent's responses on the CDI. At all ages, and on
      both name-known and name-unknown trials, preference for the target image
      increased significantly from baseline when infants heard the target's label. This
      discrepancy suggests that parental report underestimates infants' word knowledge.

PMID- 18062357
TI  - Pronouns and verbs in adult speech to children: a corpus analysis.
AB  - Assessing whether domain-general mechanisms could account for language
      acquisition requires determining whether statistical regularities among surface
      cues in child directed speech (CDS) are sufficient for inducing deep syntactic
      and semantic structure. This paper reports a case study on the relation between
      pronoun usage in CDS, on the one hand, and broad verb classes, on the other. A
      corpus analysis reveals statistical regularities in co-occurrences between
      pronouns and verbs in CDS that could cue physical versus psychological verbs. A
      simulation demonstrates that a simple statistical learner can acquire these
      regularities and exploit them to activate verbs that are consistent with
      incomplete utterances in simple syntactic frames. Thus, in this case, surface
      regularities ARE sufficiently informative for inducing broad semantic categories.
      Children MIGHT use these regularities in pronoun/ verb co-occurrences to help
      learn verbs, although whether they ACTUALLY do so remains a topic of ongoing
      research.

PMID- 18062358
TI  - Polysyllabic units in the vocalizations of children from 0;6 to 1;11: intonation
      groups, tones and rhythms.
AB  - Previous studies have suggested that intonation development in infants and
      toddlers reflects an interaction between physiological and linguistic influences.
      The immediate background research for this study, however, was based on
      vocalizations that were only one syllable in length. By extending the analysis to
      polysyllabic utterances, the present study evaluated a broader range of
      physiological constraints on intonation production than the maximally simple
      context of monosyllabic utterances had permitted. The width and direction of
      pitch change across one- and two-syllable nuclear tones were acoustically
      analyzed in utterances produced by 60 children between the ages of 0;6 and 1;11.
      The results showed that the children controlled the characteristic intonation
      pattern of English monosyllables by the age of 1;6-1;8. However, even the
      youngest groups of children produced relatively robust and adult-like intonation
      contours when the tone-bearing string was polysyllabic, suggesting that the
      trochaic or dactylic foot is the natural 'unmarked' unit of tone production. The
      asymmetrical results for one- versus two-syllable tones support the conclusion
      that width of pitch change largely reflects physiological universals in
      children's earliest vocalizations and language-specific learning after the age of
      1;6. Implications of the findings are also discussed in relation to the Trochaic
      Template Hypothesis. It is concluded that a bias for trochaic rhythms that some
      children demonstrate could be based, in part, on the child's sensitivity to
      physiological constraints on the velocity and range of intonational pitch change.

PMID- 18062359
TI  - Getting and maintaining attention in talk to young children.
AB  - When two people talk about an object, they depend on joint attention, a
      prerequisite for setting up common ground in a conversational exchange. In this
      study, we analyze this process for parent and child, with data from 40 dyads, to
      show how adults initiate joint attention in talking to young children (mean ages
      1;6 and 3;0). Adults first get their children's attention with a summons (e.g.
      Ready?, See this?), but cease using such forms once children give evidence of
      attending. Children signal their attention by looking at the target object,
      evidence used by the adults. Only at that point do adults begin to talk about the
      object. From then on, they use language and gesture to offer information about
      and maintain attention on the target. The techniques adults rely on are
      interactive: they establish joint attention and maintain it throughout the
      exchange.

PMID- 18062360
TI  - The acquisition of two phonetic cues to word boundaries.
AB  - The study evaluated whether durational and allophonic cues to word boundaries are
      intrinsic to syllable production, and so acquired with syllable structure, or
      whether they are suprasyllabic, and so acquired in phrasal contexts. Twenty
      preschool children (aged 3;6 and 4;6) produced: (1) single words with simple and
      complex onsets (e.g. nail vs. snail); and (2) two-word phrases with intervocalic
      consonant sequences and varying boundary locations (e.g. this nail vs. bitty
      snail). Comparisons between child and adult control productions showed that the
      durational juncture cue was emergent in the four-year-olds' productions of two
      word phrases, but absent elsewhere. In contrast, the allophonic cue was evident
      even in the three-year-olds' productions of single words. Perceptual judgments
      showed that age- and type-dependent acoustic differences translated into
      differences in listener behavior. The differential acquisition of the two
      juncture cues is discussed with reference to the acquisition of articulatory
      timing control.

PMID- 18062361
TI  - Redirective labels and early vocabulary development.
AB  - Parents' object labels can be distinguished by whether the child is already
      attending to the object (follow-in) or not (lead-in). Lead-in labels have been
      found to be associated with low vocabulary. The current study examines whether
      the relation between lead-in labels and child vocabulary is influenced by whether
      the child's attention is redirected. Eighteen mother-infant dyads were videotaped
      at 1;2, 1;6 and 1;10. Results indicate that parents' use of successful lead-in
      labels is positively correlated with children's vocabulary, whereas use of
      unsuccessful labels is negatively correlated. Finally, use of gesture is
      associated with the redirective success of lead-in labels.

PMID- 18062363
TI  - Two-year-olds differentially disambiguate novel words and facts.
AB  - When presented with a pair of objects, one familiar and one unfamiliar, and asked
      to select the referent of a novel word, children reliably demonstrate the
      disambiguation effect and select the unfamiliar object. The current study
      investigated two competing word learning accounts of this effect: a pragmatic
      account and a word learning principles account. Two-, three- and four-year-olds
      were presented with four disambiguation conditions, a word/word, a word/fact, a
      fact/word and a fact/fact condition. A pragmatic account predicted disambiguation
      in all four conditions while a word learning principles account predicted
      disambiguation in the word/word and fact/word conditions. Results indicated that
      children disambiguated in word/word and fact/word conditions and two-year-olds
      disambiguated at above chance levels in the word/word condition but at BELOW
      chance levels in the fact/fact condition. Because disambiguation varied both as a
      function of age and condition these findings are presented as challenges to a
      pragmatic account of the disambiguation effect.

PMID- 18062362
TI  - Two-year-olds' productivity with verbal inflections.
AB  - Previous research has examined children's ability to add inflections to nonsense
      words. The current experiments were designed to determine whether children,
      ranging in age from 1;9 to 2;10 (N = 34), could demonstrate productivity by
      dropping verbal inflections. In Experiment 1, children added -ed and -ing to
      novel stems, and dropped them from novel inflected forms and did so largely
      appropriately. In Experiment 2, they dropped -ing from verbs, but not from nouns,
      suggesting that when young children drop inflections they tend to do so
      appropriately, and not simply for ease of pronunciation.

PMID- 18062364
TI  - Nouns and verbs in the vocabulary acquisition of Italian children.
AB  - The vocabulary development of 24 Italian children aged between 1;4 and 1;6 at the
      beginning of the study was longitudinally monitored on a monthly basis using the
      Italian version of the MacArthur Communicative Development Inventory drawn up by
      their mothers. This study analyzes data from children for whom two sampling
      stages were available; the first corresponding to a vocabulary size as close as
      possible to 200 words (mean 217, range 167-281), the second to a vocabulary size
      ranging from 400 to 650 words (mean 518, range 416-648). The children's
      vocabulary composition was analyzed by calculating, for each sampling stage, the
      percentage of common nouns, verbs and closed-class words. The increase in
      percentage points of the various lexical items between the first and second
      sampling stages was also analyzed. Data confirmed the predominance of nouns over
      verbs and closed-class words at both sampling stages, while verbs and closed
      class words showed a higher percentage increase than nouns. The results provide
      evidence that children who reached the first sampling point at an earlier age had
      a higher percentage of nouns than children who reached the same stage at an older
      age. However, in the passage from the first to the second sampling point no
      relationship emerged between a style of acquisition based on the acquisition of
      nouns and an increase in the rate of vocabulary growth.

PMID- 18062365
TI  - Access and coverage critical, but other issues need air time too.

PMID- 18062366
TI  - Catholic leaders speak out on health reform in California.

PMID- 18062367
TI  - Facing disasters as a "community of we".

PMID- 18062368
TI  - The sacred encounter in outreach.

PMID- 18062369
TI  - Disaster planning after Katrina. Louisiana hospitals are partnering to build new
      models of community response.

PMID- 18062370
TI  - A matrix for ethical decision making in a pandemic. The Oregon tool for emergency
      preparedness.

PMID- 18062371
TI  - Faith-based organizations and pandemic preparedness. Church-related groups will
      be vital partners in getting ready for an influenza pandemic.

PMID- 18062372
TI  - Recovering from a flu pandemic. For hospitals, recovery can be as demanding as
      the event itself.

PMID- 18062373
TI  - All God's sick children. One city's response to the flu pandemic of 1918.

PMID- 18062374
TI  - Nutrition and hydration. The CDF response, in perspective.

PMID- 18062375
TI  - Rural hospitals and the "5 Million Lives Campaign". Catholic Health Initiatives
      is encouraging its smaller facilities to join a patient-safety effort.

PMID- 18062376
TI  - Using investments to work for community health. Socially responsible investment
      programs help carry a faith-based message.

PMID- 18062377
TI  - Beyond the hierarchy. Seven innovations have enabled this executive team to
      become more productive.

PMID- 18062378
TI  - The privilege of continuing his work. Some thoughts on quality, safety, and the
      mission of Catholic health care.

PMID- 18062379
TI  - Report on a theological dialogue on the principle of cooperation.

PMID- 18062380
TI  - Disaster preparedness is everyone's responsibility. HHS's assistant secretary for
      preparedness and response talks about how we all have a role to play in getting
      ready for pandemics and disasters.

PMID- 18062381
TI  - Extending an ethics program with information technology.

PMID- 18062382
TI  - Savannah facility has a "sister-hospital" partnership with a Guatemalan
      organization.

PMID- 18062383
TI  - Giving care in Iraq.

PMID- 18062384
TI  - Human performance optimization: an evolving charge to the Department of Defense.
AB  - Uniformed Services University of the Health Sciences hosted a conference in June
      2006 entitled "Human Performance Optimization in the Department of Defense:
      Charting a Course for the Future" with the goal of developing a strategic plan
      for human performance optimization (HPO) within the Department of Defense (DoD).
      The conference identified key issues: (1) advocating for HPO at all DoD levels,
      (2) defining HPO specific to DoD requirements, (3) developing valid and
      standardized metrics for HPO, (4) translating HPO research into the operational
      community, and (5) establishing effective communication and coordination across
      military services and within the medical, research and operational communities.
      The program objectives should enhance mental and physical resilience of the war
      fighter; accelerate recovery; reduce injury and illness; provide seamless
      knowledge transfer from laboratory to line; improve the human system contribution
      to mission success; and allow the U.S. to remain in the lead in this area.

PMID- 18062386
TI  - Specific symptoms predict suicidal ideation in Vietnam combat veterans with
      chronic post-traumatic stress disorder.
AB  - Previous research documented the elevated risk of suicide and suicidal ideation
      among Vietnam veterans with post-traumatic stress disorder (PTSD). The aim of the
      current study was to examine which Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, PTSD symptom clusters are most associated with
      suicidal ideation in this population. Fifty Vietnam combat veterans enrolled in
      treatment for PTSD responded to the Beck Scale for Suicide Ideation and were
      interviewed with the Clinician-Administered PTSD Scale. In linear regression
      analysis, it was found that the reexperiencing symptom cluster was significantly
      associated with suicidal ideation but the other two symptom clusters
      (avoidance/numbing and increased arousal) were not. Furthermore, scores on a
      measure of severity of combat exposure were not found to be significantly related
      to PTSD symptoms or suicidal ideation. The results of this study suggest the
      importance of reexperiencing symptoms for predicting which individuals with
      combat-related PTSD are most at risk for suicidal ideation and behavior.

PMID- 18062385
TI  - Fleet leaders' attitudes about subordinates' use of mental health services.
AB  - Mental disorders are a significant source of medical and occupational morbidity
      for sailors. Stigma, fear of negative career impact, and subordinates concern
      about leaders' attitudes are significant barriers to the use of mental health
      services. Semistructured interviews and military policies were data sources used
      to analyze the language, knowledge, and attitudes of Navy surface fleet leaders
      about mental illness and mental health treatment using Foucault's concept of
      discourse analysis. A discourse is a system of knowledge that influences
      language, perceptions, values, and social practices. The results showed that
      leaders' concerns about sailors' mental combat readiness, not mental illness
      stigma, was the dominant discourse about mental illness and mental health
      services use. In particular, organizational differences between the surface
      warfare and the mental health communities may influence leaders' attitudes more
      than stigma. This study provides an elaborated view of mental health knowledge
      and power within a Navy community.

PMID- 18062387
TI  - Wartime burn care in Iraq: 28th Combat Support Hospital, 2003.
AB  - INTRODUCTION: The U.S. Army 28th Combat Support Hospital (CSH), an echelon III
      facility, deployed to Iraq at the start of military operations in 2003. Shortly
      after arrival, it was designated as the hospital primarily responsible for burn
      care for the U.S. military in Iraq. This report reviews the experience of the CSH
      with burn care during combat operations. METHODS: An after-action review was
      conducted during a 2-day period after the hospital's redeployment. RESULTS:
      Between April 11, 2003, and August 21, 2003, the 28th CSH treated a total of
      7,920 patients, of whom 103 (1.3%) had burns. Patients included U.S. and allied
      service members, U.S. contractors, and Iraqi prisoners of war and civilians.
      Although a CSH is designed to care for patients until they can be stabilized and
      evacuated, usually within 1 to 3 days, the length of stay for some Iraqi patients
      was as long as 53 days. Definitive care, including excision and grafting of the
      burn wound, was thus required for some Iraqi patients. The largest graft
      completed comprised 40% of the total body surface area. The largest burn survived
      involved approximately 65% of the total body surface area. Eighteen (17%) of 103
      patients returned to duty after treatment at the 28th CSH. The mortality rate for
      burn patients at the 28th CSH was 8%. Shortages of burn-experienced personnel and
      burn-specific supplies were identified during the after-action review.
      CONCLUSIONS: The CSH provided complex definitive care to burn patients in an
      austere environment. Predeployment identification of military field hospitals for
      such specialized missions, with early assignment of experienced personnel and
      materiel to these units, may improve future wartime burn care.

PMID- 18062388
TI  - Where do veterans health administration patients obtain heart, liver, and kidney
      transplants?
AB  - We sought to determine whether Veterans Health Administration (VA) enrollees use
      the VA system or the private sector for solid-organ transplantation and whether
      VA system use is associated with patients' proximity to a VA transplant center.
      Using a national VA/Medicare inpatient data set and a comprehensive New York
      State VA/private-sector inpatient data set for 1998 to 2000, we found that
      veterans enrolled in the VA system obtained approximately one-half of their liver
      transplants, but few heart and kidney transplants, in the VA system. Patients
      were much more likely to use the VA system if they lived in a VA service area
      that offered relevant transplant services. Our findings suggest that VA
      transplant centers intended to meet national needs are more likely to serve local
      residents. Furthermore, our analysis indicates that use of only the VA/Medicare
      data set may substantially underestimate VA enrollees' reliance on the private
      sector for health care services.

PMID- 18062389
TI  - Obesity in civilian adults: potential impact on eligibility for U.S. military
      enlistment.
AB  - OBJECTIVE: This study measures the prevalence in the civilian adult population of
      obesity for military enlistment. METHODS: The National Health and Nutrition
      Examination Survey for 2001-2004 was used to obtain a sample of civilian adults
      17 to 42 years of age. Weight standards for each branch of service were applied
      to determine the proportion of subjects who were over maximal weight limits and
      thus ineligible for enlistment. RESULTS: Depending on the branch of service and
      the age range, 17.9% to 54.4% of men and 20.8% to 54.9% of women were overweight
      for enlistment. Generally, there were higher prevalence rates in the older age
      groups and among women. Prevalence rates for non-Caucasian subjects were not
      higher among men but were higher among women. CONCLUSION: Large proportions of
      civilian adults are over the weight limits for military enlistment. The currently
      increasing prevalence of obesity in the civilian population may pose a challenge
      for military recruitment programs.

PMID- 18062390
TI  - Disinfection of Acinetobacter baumannii-contaminated surfaces relevant to medical
      treatment facilities with ultraviolet C light.
AB  - The efficacy of ultraviolet C (UVC) light (100-280 nm) in the decontamination of
      three hospital-related surfaces, namely, unpainted/painted aluminum (bed
      railings), stainless steel (operating tables), and scrubs (laboratory coats), was
      investigated. Acinetobacter baumannii cells were inoculated (10(5) or 10(3)
      cells) on small coupons and dried overnight in a class II biosafety cabinet.
      Drying resulted in < or =50% loss of viability. The UVC fluence of 90 J/m2 was
      observed to be very effective in the decontamination of cells from all metal
      coupon surfaces (complete killing). However, the same fluence was ineffective in
      the decontamination of scrubs. The effectiveness of two other common disinfection
      practices, that is, 15 minutes of boiling or spraying with 70% ethanol, was
      investigated for the scrubs. Although ethanol treatment was ineffective, the
      boiling treatment was very effective (complete killing). These results establish
      that metal surfaces can be decontaminated with UVC irradiation and boiling
      treatment is effective for scrub decontamination.

PMID- 18062391
TI  - Alcohol-based instant hand sanitizer use in military settings: a prospective
      cohort study of Army basic trainees.
AB  - We investigated the impact of a customized alcohol-based instant hand sanitizer
      hand-hygiene regimen in an Army basic training setting. The entire population at
      the U.S. Army Field Artillery Training Center, Fort Sill, Oklahoma, participated
      in the 13-week prospective cohort study between January 18, 2005 and April 18,
      2005. Two training battalions were randomly assigned to the control group, one to
      the primary intervention group (customized Purell Instant Hand Sanitizer regimen,
      education, reinforcement) and one to the secondary intervention group (customized
      Purell Instant Hand Sanitizer regimen). When compared to the control group,
      intervention groups experienced 40% less respiratory illness (p < 0.001), 48%
      less gastrointestinal illness (p < 0.02), 44% less lost training time (p <
      0.001), and 31% fewer health care encounters (p < 0.001). These findings suggest
      that this intervention is capable of significantly reducing illness in this
      setting and has the potential to help reduce absenteeism in the military
      workforce as a whole.

PMID- 18062392
TI  - Influence of educational status and other variables on human immunodeficiency
      virus risk perception among military personnel: a large cohort finding.
AB  - Human immunodeficiency virus (HIV) risk perception remains an effective
      determinant of HIV transmission. Although higher educational attainment has been
      associated with increased HIV risk perception, this predictor remains to be
      assessed among Nigerian military personnel (NMP). In a prospective cohort of
      2,213 NMP, the effects of education and other factors on HIV risk perception were
      assessed at baseline by using the X2 statistic and unconditional logistic
      regression. There was an inverse correlation between higher educational
      attainment and HIV risk perception in the univariate model (prevalence odds
      ratio, 0.64; 95% confidence interval, 0.52-0.79). This association persisted
      after adjustment for relevant covariates in the multivariate model (prevalence
      odds ratio, 0.70; 95% confidence interval, 0.56-0.88). Similarly, there was a
      direct correlation between use of alcohol and marijuana and HIV risk perception
      (p < 0.05). In contrast, casual sex and gender were not statistically
      significantly associated with HIV risk perception (p > 0.05). This study
      indicates an inverse correlation between educational attainment and HIV risk
      perception, as well as a direct correlation between alcohol and marijuana use and
      HIV risk perception, among NMP. Therefore, HIV prevention interventions targeted
      at NMP need to include multiple factors that may affect risk perception
      regardless of the educational status of the participants.

PMID- 18062393
TI  - Improving the dental fitness of the British Army by changing the strategy for
      dental care provision for recruits from a vertically equitable model to a
      horizontally equitable model.
AB  - BACKGROUNDd: The dental health of the British Army has been reported as being in
      decline for the past 10 years, and this is having a significant impact on
      operations. One of the major factors in the decline is the increasing number of
      recruits who enlist with outstanding dental treatment needs. The current policy
      for provision of routine dental care to recruits targets resources toward those
      with the worst dental health and provides only emergency dental care for the
      remainder.AIMSs: The goal was to review recruit dental care provision, to
      determine whether improvements in the overall dental health of the trained Army
      could be made during recruit training.RESULTSs: It was found that >85% of recruit
      dental treatment need could be met with the routine provision of 2 hours of
      dental treatment during training.CONCLUSIONn: A horizontally equitable model of
      recruit dental care, whereby all recruits access routine dental care during
      training, has been recommended to and accepted by the chain of command.

PMID- 18062394
TI  - Managing health and finance: challenges, outcome, and control in the Israel
      Defense Forces.
AB  - BACKGROUND: The Ministry of Defense budget constitutes 16% of the state budget.
      The budget for the Ministry of Health and for civilian health care is derived
      from the state budget. The health care funds receive their budgets from several
      sources. The capitation formula, which is determined by law, is the main factor
      that affects the size of the budget each fund receives. OBJECTIVE: The objective
      of this study is to describe the manner of planning, managing, monitoring, and
      controlling the budget allocated to medical services, which is a public budget
      for soldiers. METHODS: Several parameters are suggested for comparison, including
      the interface with the civilian health system, the method for budgeting a health
      care system, possible results of managing a medically centered budget, and the
      possibilities for monitoring the provided services. We also examine the potential
      for decentralization of authority. CONCLUSIONS: Managing the budget and locating
      appropriate alternatives, as well as the availability and accessibility of
      medical services, are important for procurement and for forming contracts with
      both military and civilian systems. Turnover based on updated information might
      serve to improve future health services.

PMID- 18062395
TI  - Characteristics of heart rate variability in war veterans with post-traumatic
      stress disorder after myocardial infarction.
AB  - OBJECTIVE: The goal of the study was to evaluate differences in heart rate
      variability (HRV) among post-myocardial infarction (MI) patients, depending on
      their participation in the Croatian war and on established diagnoses of post
      traumatic stress disorder (PTSD). METHODS: The study included 34 male war
      veterans with diagnosed PTSD who had suffered a first MI and 34 age-matched post
      MI patients without PTSD. Cardiac autonomic balance was evaluated through HRV
      analysis. RESULTS: There were no differences in the mean R-R interval or overall
      HRV between the analyzed groups. Post-MI patients with PTSD had lower values for
      the square root of the mean of squared successive differences in R-R intervals (p
      = 0.02), the percentage of R-R intervals that were > or =50 milliseconds
      different from the previous interval (p = 0.03), and the high-frequency component
      (p = 0.03) but had higher values for the low-frequency component (p = 0.01) and
      the low-frequency/high-frequency ratio (p = 0.02), compared with post-MI patients
      without PTSD. CONCLUSION: Post-MI patients with PTSD have higher sympathetic and
      lower parasympathetic heart rate modulation activity, compared with patients with
      MI and no PTSD.

PMID- 18062396
TI  - Airway hyperreactivity in asymptomatic military personnel.
AB  - OBJECTIVES: Asthma is frequently diagnosed in military personnel despite strict
      guidelines that disqualify persons with active disease or a recent history of
      asthma. It is generally considered incompatible with military service, because of
      the regular physical training, outdoor training exercises, and deployments to
      remote locations. The objective of this study was to determine the prevalence of
      airway hyperreactivity in asymptomatic military personnel, as an estimate of
      subclinical reactive airway disease. METHODS: A prospective study of healthy,
      asymptomatic, military personnel with no previous history of asthma and <1 year
      on active duty status was conducted. After completion of a screening
      questionnaire, personnel underwent baseline spirometry with a portable
      spirometer. Personnel with obstructive indices (based on published guidelines)
      and matched control subjects participated in an exercise test (1.5-mile run),
      with pre- and postexercise spirometry. RESULTS: A total of 222 asymptomatic
      military personnel completed baseline spirometry, and 31 (14%) were found have
      airway obstruction. A normal matched control group of 31 military personnel and
      26 personnel with obstruction performed exercise spirometry. Twenty-three percent
      of the participants with obstruction demonstrated increased airway hyper
      reactivity after exercise, based on a reduction in forced expiratory volume at 1
      second, compared with 19% of control subjects. CONCLUSIONS: Asymptomatic airway
      obstruction has a prevalence of 14% in young military personnel. A significant
      percentage of individuals also have evidence of worsening obstruction during
      exercise. These data suggest that screening spirometry may identify early
      reactive airway disease in asymptomatic individuals and should be considered as a
      method to identify persons predisposed to developing symptomatic asthma.

PMID- 18062397
TI  - Adenovirus-associated acute respiratory disease in healthy adolescents and
      adults: a literature review.
AB  - Adenovirus-associated acute respiratory disease (AARD) is well documented in the
      U.S. military, but little information is readily available on its occurrence in
      other healthy populations that might also benefit from adenovirus vaccines. We
      reviewed publications on AARD in non-U.S. military,immunocompetent, young adults
      in group-living settings. Since adenovirus disease can be severe in
      immunocompromised and pediatric patients, we also considered AARD in healthcare
      workers. We evaluated 83 publications, published between 1950 and 2005,
      concerning 22 countries. Most described outbreaks in foreign military recruits
      and were published before 1970. More recent reports documented outbreaks in
      student dormitories and medical facilities. The 83 reports did not provide
      evidence for AARD being a serious, persistent, contemporary concern in the
      populations studied, nor did they identify strong interest in adenovirus
      vaccines. Currently availability, sensitive, molecular diagnostic tests may
      better define the importance of AARD in populations outside the U.S. military.

PMID- 18062398
TI  - Fatal road accidents among Finnish military conscripts: fatigue-impaired driving.
AB  - The aims of the present study were to determine the current prevalence of
      personal car usage for holiday trips among Finnish conscripts and to analyze
      conscripts' fatal road accidents. The data included questionnaire data collected
      from 259 young conscripts at a garrison in southeastern Finland and data on 46
      fatal road accidents caused by conscripts during the years 1991-2004, extracted
      from the national database of fatal road accidents studied in depth. The
      questionnaire data showed that one-third (35.9%) of young Finnish conscripts had
      used personal cars to travel to or from the garrison in the preceding 2 months.
      More than one-half of them reported driving while fatigued (a majority reported
      several occasions of such driving). In addition to those driving themselves,
      41.6% of the conscripts rode at least occasionally as a passenger in a car driven
      by a fellow conscript. Analysis of the fatality data showed that one-half of the
      conscripts' fatal accidents occurred on the way to or from the garrison or while
      on duty. Falling asleep was the main cause of all conscripts' accidents (34.8%),
      with the largest proportion occurring when departing for leave (42.9%). Haste
      (including speeding) was the second greatest factor contributing to accidents
      occurring on the way to or from the garrison (26.1%), whereas drunk driving
      (22.7%) and suspected suicides (18.2%) were typical of accidents occurring on
      leave.

PMID- 18062399
TI  - Immediate insertion of a semirigid penile prosthesis for refractory ischemic
      priapism.
AB  - The insertion of a penile prosthesis for reduction of ischemic priapism has
      previously been described for cases of sickle cell disease, delayed presentation,
      or failure of previous shunt surgery. We report the first case of immediate
      insertion of a malleable prosthesis as primary surgical therapy for refractory
      ischemic priapism in a patient with known preexisting erectile dysfunction. We
      propose a novel management algorithm incorporating the acute insertion of a
      penile prosthesis as an effective option in the management of refractory ischemic
      priapism.

PMID- 18062400
TI  - Significance of cultural beliefs in presentation of psychiatric illness: a case
      report of selective mutism in a man from Nepal.
AB  - A 22-year-old active duty E1 Nepalese male who recently emigrated from Nepal
      suddenly exhibited strange behaviors and mutism during Advanced Individual
      Training. After receiving care from a hospital near his unit, he was transferred
      to Walter Reed Army Medical Center Inpatient Psychiatry for further evaluation
      and treatment. Although he was admitted with a diagnosis of psychosis not
      otherwise specified (NOS), after consideration of cultural factors and by ruling
      out concurrent thought disorder, a diagnosis of selective mutism was made. To our
      knowledge this is the first reported case of selective mutism in a soldier. This
      case serves as a reminder of the need for cultural awareness during psychological
      evaluation, diagnosis, and treatment of patients.

PMID- 18062401
TI  - Hepatitis E virus infection in Thai troops deployed with U.N. peacekeeping
      forces.
AB  - The hepatitis E virus (HEV) is thought to be endemic throughout much of the
      world, particularly where sanitary infrastructure remains inadequate. HEV has
      been considered a military health threat and has been reported in several
      military environments. This study determined HEV seroconversion (defined by a 4
      fold increase in antibody titers) occurring in Thai soldiers deployed to the HEV
      endemic areas of East Timor, Afghanistan, and Iraq, as part of the U. N.
      multinational forces. With an average deployment of 6.4 months, the annualized
      seroconversion rates after deployments to East Timor, Afghanistan, Burundi, and
      Iraq were 1.9%, 4.6%, 4.6%, and 3.9%, respectively.

PMID- 18062402
TI  - Constrictive pericarditis: a cause of exertion-induced dyspnea in a soldier with
      a prior sternotomy.
AB  - Diagnosing the underlying etiology of dyspnea on exertion in adults can be
      challenging, often requiring the clinician to distinguish cardiac or pulmonary
      pathological conditions from metabolic, neurological, or hematological conditions
      or from chest wall abnormalities. We report such a case involving a 29-year-old,
      male, active duty Army soldier. With a history of a median sternotomy, symptoms
      of right- and left-side heart failure, and examination findings suggesting
      elevated right atrial pressure, pericardial disease was pursued. Echocardiography
      and cardiac catheterization revealed constrictive physiological features, namely,
      elevation and near-equalization of right- and left-side pressures and ventricular
      interdependence, whereas computed tomography illustrated pericardial thickening,
      ultimately leading to the diagnosis of constrictive pericarditis. The patient was
      treated with a complete pericardiectomy, leading to symptom resolution and
      improved exercise capacity. This case report of a rare condition offers a concise
      etiological and physiological overview of constrictive pericarditis and
      demonstrates an effective multimodal diagnostic approach. The scientific evidence
      provided may assist general practitioners in making decisions to differentiate
      this clinical condition from similar cardiac or cardiopulmonary conditions.

PMID- 18062403
TI  - Radiology corner. Worst headache of life.

PMID- 18062404
TI  - Salivary glands epithelial and myoepithelial cells are major vitamin D targets.
AB  - Receptor binding with 3H-1,25(OH)2 vitamin D3 (vitamin D) and its oxygen analog
      3H-OCT is demonstrated in rat, hamster, and mice submandibular, sublingual and
      parotid glands, using receptor microautoradiography high-resolution imaging.
      Nuclear uptake and retention of radiolabeled compound exist strongest in
      epithelial cells of striated ducts, granular convoluted tubules and in
      myoepithelial cells throughout, scattered in epithelial cells of intercalated
      ducts and relatively low in cells of serous and mucous acini. Deposition and
      retention of radiolabeled compound is also observed in interstitial spaces. The
      specific nuclear localization with vitamin D and its analogue OCT, which is
      absent with 3H-(OH) vitamin D3 and in competition with excess non-radioactive
      vitamin D, indicates involvement of vitamin D in the multi-hormonal regulation of
      salivary gland secretion, excretion, and cell proliferation. These data--together
      with previously recognized similar receptor binding in esophagus, gastric glands,
      entero-endocrine cells, pyloric muscle, and generative and absorptive epithelium
      of the small intestine and colon, point to the importance of vitamin D for the
      digestive system regulation of functions and maintenance with related therapeutic
      potentials.

PMID- 18062405
TI  - Identification of CYP3A4 as the primary cytochrome P450 responsible for the
      metabolism of tandospirone by human liver microsomes.
AB  - The present study was carried out to characterize the human P450 isoforms
      involved in the metabolism of tandospirone, an anxiolytic agent known for its
      superior efficacy and safety. Among 11 yeast-expressed recombinant P450 isoforms
      tested, CYP2D6 and CYP3A4 exhibited the highest tandospirone metabolic activity.
      Although there was no qualitative difference between the two isoforms, a
      quantitative difference in metabolite profiling was found i.e., M4 (hydroxylation
      of the pyrimidine ring) was the major metabolite formed with CYP2D6 while M2
      (hydroxylation of the norbornan ring) and 1-PP (oxidative cleavage of the butyl
      chain) predominated with CYP3A4. The metabolite profile on incubation with CYP3A4
      was qualitatively and quantitatively similar to that obtained with human liver
      microsomes. In vitro intrinsic clearance (CLint) values derived from kinetic
      analysis using both P450 isoforms were similar (2.2 and 1.6 ml/min/nmol P450),
      but the hepatic content of CYP3A4 was found to be more abundant than that of
      CYP2D6. The in vitro metabolism of tandospirone by human liver microsomes was
      markedly inhibited by ketoconazole (a CYP3A4 inhibitor) but not by quinidine (a
      CYP2D6 inhibitor). These results indicate that the metabolism of tandospirone by
      human liver microsomes primarily involves CYP3A4, and to a lesser extent CYP2D6.

PMID- 18062406
TI  - Transport of quercetin di-sodium salt in the human intestinal epithelial Caco-2
      cell monolayer 139.
AB  - Quercetin di-sodium salt (QDS), a water-soluble derivative of quercetin (Q), is a
      potent free radical scavenger. The aim of this study was to examine the in vitro
      intestinal transport of QDS compared to that of Q using the Caco-2 human
      intestinal epithelial cell line. The apical (A) to basolateral (B) transport of
      QDS was found to be higher than the B to A transport of this compound. This
      polarized transport involved the presence of a carrier protein system. The
      involvement of the sodium/glucose transporter-1 (SGLT-1) was shown by using
      phloridzin, a selective inhibitor of this conveyor system. However, the transport
      of Q was not affected by this inhibitor. Moreover, the influx of QDS was pH
      sensitive and decreased at pH 5.5 compared with that observed at pH 7.4 and 6.5.
      The permeability of QDS was 10-fold higher than that of Q. This could be
      explained by the involvement of SLGT-1 and the absence of an active efflux pump
      in the absorption of QDS in comparison with Q. This finding was supported by
      comparing the solubility of Q with that of QDS. This study indicates that both
      the higher solubility of QDS and its dependence on the SGLT-1 transport system
      resulted in more efficient permeability compared to Q.

PMID- 18062407
TI  - Stem cell renewal and contraction of the tunica media caused by a damaged blood
      vessel following a thick needle stab.
AB  - A marked difference in the healing process of the inferior vena cava in rats
      following a stab with a 17-G (1.48 mm phi) ultrahard zirconium ceramic (Zr)
      needle and with a common stainless steel (St) needle (also 1.48 mm phi was
      observed. This was investigated in vivo by histological imaging and biochemical
      micro-autoradiographic imaging using [2-(14)C]-thymidine as a biomarker in vivo.
      On the first day after the stab with either, the Zr or the St injection needle,
      the tunica adventitia showed the most pronounced damage, as evidenced by a large
      puncture wound characterized by blood congestion, but with few inflammatory cells
      being observed. A marked contraction of the tunica media was observed. The depth
      of the injury reached the tunica layer, but amounted to less than 1/3 of the
      needle diameter. Loose fragments of the endothelial lining were detected,
      together with scattered red corpuscles. The survival rate of the experimental
      animals amounted to less than 40% on the 3rd day after the stab by either the Zr
      or St needle, due to the large needle diameter. In addition, histological imaging
      of the wound area in the endothelial layer and tunica media showed considerable
      congestion and inflammation, which limited the evaluation of the regeneration
      status of the inferior vena cava of the surviving animals. Results were obtained
      from a few animals that displayed satisfactory recovery status. On the 3rd day
      after the stab by either the Zr or St injection needle, a relatively large
      proportion of the hemostatic clots became incorporated into the collagenous
      tissue, i.e. the tunica adventitia. A marked contraction of the tunica media was
      also observed, similar to that on the 1st day, following the needle injury. In
      the case of the endothelium (tunica intima), the injury caused by the Zr needle
      was reinfiltrated by adult stem cells 3 days after the stab, but the tunica
      media, composed of endothelial cells, still contained relatively contracted
      collagenous material. In addition, several interesting cell colonies were
      observed in the medial layer at the short distance from the boundary of the
      damaged tissue. It was assumed that these colonies produced medial tissue
      composed of collagenous supporting tissue or smooth muscle cells. In the
      experiment using the St needle, the incorporation of [2-(14)C]-thymidine into the
      nucleus of the stem cells was observed in the small capillaries of the tunica
      media, but not in the support cells of the latter.

PMID- 18062408
TI  - Absorption, metabolism, and excretion of 14C-labeled tapentadol HCl in healthy
      male subjects.
AB  - Tapentadol is a novel, centrally acting oral analgesic with a dual mode of action
      that has demonstrated efficacy in preclinical and clinical models of pain relief.
      The present study investigated and characterized the absorption, metabolism, and
      excretion of tapentadol in humans. Four healthy male subjects received a single
      100-mg oral dose of 3-[14C]-labeled tapentadol HCl for evaluation of the
      pharmacokinetics of the drug and the excretion balance of radiocarbon. The
      concentration-time profiles of radiocarbon in whole blood and serum and
      radiocarbon excretion in the urine and feces, and the expired CO2 were
      determined. The serum pharmacokinetics and excretion kinetics of tapentadol and
      its conjugates were assessed, as was its tolerability. Absorption was rapid (with
      a mean maximum serum concentration [Cmax], 2.45 microg-eq/ml; a time to Cmax,
      1.25-1.5 h), and the drug was present primarily in the form of conjugated
      metabolites (conjugated:unconjugated metabolites = 24:1). Excretion of
      radiocarbon was rapid and complete (>95% within 24 h; 99.9% within 5 days) and
      almost exclusively renal (99%: 69% conjugates; 27% other metabolites; 3% in
      unchanged form). No severe adverse events or clinically relevant changes in vital
      signs, laboratory measurements, electrocardiogram recording, or physical
      examination findings were reported. In our study group, it was found that a
      single oral dose of tapentadol was rapidly absorbed, then excreted into the
      urine, primarily in the form of conjugated metabolites, and was well tolerated.

PMID- 18062409
TI  - Metabolic fate of the antipsychotic agent, mazapertine, in man--API-MS and MS/MS
      identification of urinary metabolites.
AB  - The in vivo metabolism of the antipsychotic agent mazapertine was studied after
      oral administration of mazapertine succinate (40 mg/subject) to two healthy
      volunteers, and urine (0-24 hours) was obtained for metabolite identification
      using API-ionspray LC/MS and MS/MS analysis. Unchanged mazapertine (12% of the
      sample) plus 10 metabolites were profiled, quantified, and tentatively identified
      on the basis of MS data, Glusulase-hydrolysis, and by comparison to synthetic
      samples. The formation of mazapertine metabolites are via seven metabolic
      pathways: (1) phenylhydroxylation, (2) piperidyl oxidation, (3) O-dealkylation,
      (4) N-dephenylation, (5) oxidative N-debenzylation, (6). depiperidylation, and
      (7) glucuronidation. Pathways 1, 2, 5 and 7 formed 4-OH-phenyl-mazapertine (M1,
      18%) and 4-OH-piperidyl (M2, 14%)-mazapertine, carboxybenzoylpiperidine (M8, 10%)
      and its glucuronide (M9, 14%) as four major metabolites. Six moderate and minor
      metabolites (M3-M7 & M10; each < or =10%) formed via a combination of pathways 1
      6. Mazapertine is extensively metabolized in humans.

PMID- 18062410
TI  - Releasing characteristics of phosphorus and other substances during thermal
      treatment of excess sludge.
AB  - The releasing characteristics of phosphorus, nitrogen compounds, organics, and
      some metal cations during thermal treatment of excess sludge were investigated.
      It was found that during heating not only phosphorus, but also nitrogen
      compounds, organics, and some metal cations could be released in abundance. The
      maximum orthophosphate (ortho-P) release of about 90 mg/L in concentration was
      observed at 50 degrees C in 1 h. Except for volatile fatty acids (VFAs),
      comparatively little total nitrogen (TN), total organic carbon (TOC), and metal
      cations were released at the same time. Such results might favor further process
      of phosphorus recovery. VFAs were considerably released only at 50 degrees C.
      Acetic, butyric, and propionic acid were the most abundant components in turn and
      their releasing profiles exhibited good linear relationship with time (R2 =
      0.9977, 0.9624, and 0.8908, respectively). The concentrations of Mg2+ and K+
      increased with time and temperature during thermal treatment, but Ca2+ decreased.
      The release of Mg2+ and K+ agreed well with TP release (R2 = 0.9892 and 0.9476,
      respectively). Temperature in the experimental range had very little impact on
      the linear relationships, especially of Mg2+. Moreover, the parameter of mixed
      liquor suspended solids (MLSS) was found to be an important factor for thermal
      sludge treatment as the released ortho-P and total phosphorus (TP) at 50 degrees
      C increased more than one-fold when MLSS was increased from 4000 to 8000 mg/L.

PMID- 18062411
TI  - Hydrodynamic characteristics of a four-compartment periodic anaerobic baffled
      reactor.
AB  - Periodic anaerobic baffled reactor (PABR) is a novel reactor based on the design
      concept of anaerobic baffled reactor (ABR). Residence time distribution (RTD)
      studies on both clean and working reactors at the same hydraulic residence time
      (HRT) of 2 d were carried out to investigate the dead spaces and mixing patterns
      in PABRs at different organic loading rates (OLRs) in various switching manners
      and frequencies. The results showed that the fraction of dead space in PABR was
      similar to that in ABR, which was low in comparison with other reactor designs.
      Dead space may be divided into two categories, hydraulic and biological. In RTD
      studies without biomass, the hydraulic dead space in the PABR run in an "every
      second" switching manner with T = 2 d was the lowest whereas that in the PABR run
      in a T = infinity (ABR) switching manner was the highest. The same trend was
      obtained with the total dead space in RTD studies with biomass no matter what the
      OLR was. Biological dead space was the major contributor to dead space but
      affected decreasingly at higher OLR whichever switching manner the PABR run in.
      The flow patterns within the PABRs were intermediate between plug-flow and
      perfectly mixed under all the conditions tested.

PMID- 18062412
TI  - Adsorption removal of phosphate from aqueous solution by active red mud.
AB  - Red mud is the waste of alumina industry and has high TiO2 and Fe2O3 content
      which are active components for the adsorption of anion pollutants. In this
      study, the uptake of phosphate by red mud activated by heat treatment and acid
      heat treatment was investigated. The factors influencing the adsorption were also
      investigated. The result showed that the red mud sample treated using acid-heat
      method at 80 degrees C with 0.25 mol/L HCl for 2 h achieved the highest phosphate
      removal. For the heat-activated red mud, the sample heated at 700 degrees C for 2
      h preformed better than the other heat treatment. Phosphate removal by the
      activated red mud was significantly pH dependent, and pH 7 was the optimal pH for
      phosphate removal. The adsorption fits Langmuir isotherm model well and the
      maximum adsorption capacities of the acid-heat activated red mud and the heat
      activated samples were 202.9 mgP/g and 155.2 mgP/g, respectively.

PMID- 18062413
TI  - Chlorobenzenes in waterweeds from the Xijiang River (Guangdong section) of the
      Pearl River.
AB  - The Xijiang River is the major source of water for about 4.5 millions of urban
      population and 28.7 millions of rural population. The water quality is very
      important for the health of the rural population. The concentration and
      distribution of chlorobenzenes (CBs) in both water and waterweeds collected from
      4 stations in the Xijiang River (Gangdong section) of the Pearl River in April
      and November were determined. The result showed that nearly every congener of CBs
      was detected. The total contents of CBs (SigmaCBs) in the river water ranged from
      111.1 to 360.0 ng/L in April and from 151.9 to 481.7 ng/L in November,
      respectively. The pollution level of CBs in the water in April was higher than
      that in November. The contents of SigmaCBs in waterweeds ranged from 13.53x10(2)
      microg/g to 38.27x10(2) microg/g dry weight (dw). There was no significant
      difference between April and November in waterweeds. The distribution of CBs in
      roots, caulis, and leaves of Vallisneria spiralis L. showed different patterns.
      The leaves mainly contained low-molecular-weight CBs (DCBs), whereas the roots
      accumulated more PCBs and HCBs. The average lgBCF(lip) (bioconcentration factor)
      of CBs ranged from 0.64 to 3.57 in the waterweeds. The spatial distribution
      character of CBs in the Xijiang River was: Fengkai County < Yunan County < Yun'an
      County < Gaoyao County according to the SigmaCBs, and the pollution deteriorated
      from the upstream to the downstream of the Xijiang River. Further analysis
      demonstrated that the discharge of waste containing CBs may be the main source of
      CBs pollution in the Xijiang River.

PMID- 18062414
TI  - Treatment of 2-phenylamino-3-methyl-6-di-n-butylaminofluoran production effluent
      by combination of biological treatments and Fenton's oxidation.
AB  - High strength refractory organic stream is produced during the production of 2
      phenylamino-3-methyl-6-di-n-butylaminofluoran (One Dye Black 2, abbr. ODB 2), a
      novel heat-sensitive material with a promising market. In this study, a
      combination of acidification-precipitation, primary biological treatment,
      Fenton's oxidation and another biological treatment was successfully used for the
      removal of COD from 18000-25000 mg/L to below 200 mg/L from the ODB 2 production
      wastewater in a pilot experiment. A COD removal of 70%-80% was achieved by
      acidification-precipitation under a pH of 2.5-3.0. The first step biodegradation
      permitted an average COD removal of 70% under an hydraulic residence time (HRT)
      of 30 h. By batch tests, the optimum conditions of Fenton's oxidation were
      acquired as: Fe2+ dose 6.0 mmol/L; H202 dose 3000 mg/L; and reaction time 6 h.
      The second step biological treatment could ensure an effluent COD below 200 mg/L
      under an HRT of 10 h following the Fenton's treatment.

PMID- 18062415
TI  - Decolorization of Blue CL-BR dye by AOPs using bleach wastewater as source of
      H2O2.
AB  - This research was focused on the investigation of the efficacy of advanced
      oxidation processes (Fenton, ozonation and UV/H2O2) for decolorization of
      reactive azo dye (Blue CL-BR) using bleach wastewater as possible source of H202.
      All the experiments were performed on the laboratory scale set-up. The results
      showed that colour removal efficiencies by UV or bleach (H2O2) alone were not so
      efficient. Fenton process with bleach wastewater was found to be the most
      effective at process conditions such as pH of 3 and H2O2/Fe2+ ratio of 24:1,
      resulting in 64% colour removal. Almost complete colour removal, i.e., 99% and
      95% were achieved by UV/H2O2 and UV/bleach wastewater in 30 and 60 min,
      respectively. Ozonation proved an efficient method for decolorization of Blue CL
      BR dye at alkaline pH. It was possible to achieve 98% colour removal with 30 min
      of ozonation at pH 9. The colour removal of dye was found to follow first order
      kinetics.

PMID- 18062416
TI  - Effects of humic acid coatings on phenanthrene sorption to black carbon.
AB  - Black carbon (BC) can strongly adsorb hydrophobic organic compounds (HOCs). The
      HOC sorption to coated BC could be attenuated in soil and sediment compared with
      that of the parent BC. To study the potential causes of the sorption attenuation,
      humic acid (HA) and BC were isolated. Phenanthrene (PHE) was selected as the
      representative of HOCs. BC was coated with the precipitated HA. The PHE sorption
      to the HA-coated BC was determined. The HA coatings on BC could result in the
      significant sorption attenuation of PHE to BC. The attenuation varied in
      different HA origin and was positively correlated to the aromaticity of HA. The
      attenuation could be explained by the direct competition between HA and PHE for
      the available sorption sites on BC and the reduction of the available sorption
      sites as a result of the pore blockage of BC caused by the HA coatings.
      Therefore, the HA coatings on BC was one potential cause of the attenuation of
      HOC sorption to BC in soil and sediment.

PMID- 18062417
TI  - Water quality characteristics along the course of the Huangpu River (China).
AB  - Huangpu River is about 114.5 km from upriver Dianfeng to downriver Wusong, near
      the estuary of the Yangtze River. It plays a key role in supplying water for
      production, life, shipment and irrigation. With the industrial development, the
      pollution of the Huangpu River has become serious recently. The biological oxygen
      demand (BOD), total nitrogen (TN), total phosphorus (TP), oil, phenol and
      suspended solids (SS) were lower in the upstream sites than in the downstream
      sites, indicating pollutants being input along its course. Water quality was the
      worst in the Yangpu site, near the center of Shanghai City. Dissolved oxygen (DO)
      content was less than 2 mg/L in the site of Yangpu in July. Among relations
      between thirteen characteristics, relations between BOD, DO, TN, TP, NH4(+)-N,
      NO3(-)-N and the count of total bacteria or Escherichia coli were significant and
      interdependent. Inner relationships between these main characteristics in the
      Huangpu River were studied. High nutrient concentration led to growth of
      microorganisms, including E. coli. Degradation of organic matters and respiration
      of bacteria made oxygen concentration decreased in the water body, and DO was a
      key factor for nitrification-denitrification process of nitrogen. In the Yangpu
      site, DO was decreased to less than 3.0 mg/L with BOD higher than 7.5 mg/L in May
      and July. Low DO concentration will decrease nitrification rate. Nitrification
      need at higher DO value than other organic substrate oxidation. Consequently,
      river water contains low NO3(-)-N values with high amounts of TN and NH4+-N
      there. This will block the self-purification of surface water, by decreasing the
      rate of nitrification-denitrification transformation process in the water body.

PMID- 18062418
TI  - Changes in groundwater levels and the response of natural vegetation to transfer
      of water to the lower reaches of the Tarim River.
AB  - Restoration and reconstruction of the degraded Tarim River ecosystem is an
      important challenge. A goal of an ecological water conveyance project is to
      protect and restore the natural vegetation in the lower reaches of Tarim River by
      transferring water from Bosten Lake, through the river channel, to the lower
      reaches. This study describes the changes in groundwater depth during the water
      transfer and the respondence of riparian vegetation to alterations in groundwater
      levels. The results indicate that groundwater depth along the Tarim River channel
      has a significant spatial-temporal component. Groundwater levels closest to the
      river channel show the most immediate and pronounced changes as a response to
      water transfer while those further away respond more slowly, although the
      observed change appears to be longer in duration. With a rise in the groundwater
      level, natural vegetation responded with higher growth rates, biomass and
      biodiversity. These favorable changes show that it is feasible to protect and
      restore the degraded natural vegetation by raising the groundwater depth. Plant
      communities are likely to reflect the hysteresis phenomenon, requiring higher
      water levels to initiate and stimulate desired growth than what may be needed to
      maintain the plant community. Because different species have different ecologies,
      including different root depths and densities and water needs, their response to
      increasing water availability will be spatially and temporally heterogenous. The
      response of vegetation is also influenced by microtopography and watering style.
      This paper discusses strategies for the protection and restoration of the
      degraded vegetation in the lower reaches of the Tarim River and provides
      information to complement ongoing theoretical research into ecological
      restoration in arid or semi-arid ecosystems.

PMID- 18062419
TI  - Measurement of in-vehicle volatile organic compounds under static conditions.
AB  - The types and quantities of volatile organic compounds (VOCs) inside vehicles
      have been determined in one new vehicle and two old vehicles under static
      conditions using the Thermodesorber-Gas Chromatograph/Mass Spectrometer (TD
      GC/MS). Air sampling and analysis was conducted under the requirement of USEPA
      Method TO-17. A room-size, environment test chamber was utilized to provide
      stable and accurate control of the required environmental conditions
      (temperature, humidity, horizontal and vertical airflow velocity, and background
      VOCs concentration). Static vehicle testing demonstrated that although the amount
      of total volatile organic compounds (TVOC) detected within each vehicle was
      relatively distinct (4940 microg/m3 in the new vehicle A, 1240 microg/m3 in used
      vehicle B, and 132 microg/m3 in used vehicle C), toluene, xylene, some aromatic
      compounds, and various C7-C12 alkanes were among the predominant VOC species in
      all three vehicles tested. In addition, tetramethyl succinonitrile, possibly
      derived from foam cushions was detected in vehicle B. The types and quantities of
      VOCs varied considerably according to various kinds of factors, such as, vehicle
      age, vehicle model, temperature, air exchange rate, and environment airflow
      velocity. For example, if the airflow velocity increases from 0.1 m/s to 0.7 m/s,
      the vehicle's air exchange rate increases from 0.15 h(-1) to 0.67 h(-1), and in
      vehicle TVOC concentration decreases from 1780 to 1201 microg/m3.

PMID- 18062420
TI  - Sorption of 1-naphthol by plant cuticular fractions.
AB  - The contribution of aliphatic-rich plant biopolymer to sorption of hydrophobic
      organic compounds is significantly important because of their preservation and
      accumulation in the soil environment, but sorption mechanism is still not fully
      understood. In this study, sorption of 1-naphthol by plant cuticular fractions
      was examined to better understand the contributions of respective fraction.
      Toward this end, cuticular materials were isolated from the fruits of tomato by
      chemical method. The tomato cuticle sheet consisted of waxes (6.5 wt%), cuticular
      monomer (69.5 wt%), and polysaccharide (24.0 wt%). Isotherms of 1-naphthol to the
      cuticular fractions were nonlinear (N value (0.82 - 0.90)) at the whole tested
      concentration ranges. The K(oc)/K(ow) ratios for bulk cuticle (TC1), dewaxed
      cuticle (TC2), cutin (TC4), and desugared cuticle (TC5) were larger than unity,
      suggested that tomato bulk cuticle and cutin are much powerful sorption medium.
      Sorption capability of cutin (TC4) was 2.4 times higher than the nonsaponifiable
      fraction (TC3). The 1-naphthol interactions with tomato cuticular materials were
      governed by both hydrophobic-type interactions and polar (H-bonding)
      interactions. Removal of the wax and polysaccharide materials from the bulk
      tomato cuticle caused a significant increase in the sorption ability of the
      cuticular material. There was a linear negative trend between K(oc) values and
      the amount of polysaccharides or fraction's polarities ((N+O)/C); while a linear
      positive relationship between K(oc) values and the content of cutin monomer
      (linear R2 = 0.993) was observed for present in the cuticular fractions.
      Predominant sorbent of the hydrophobic organic compounds (HOCs) in the plant
      cuticular fraction was the cutin monomer, contributing to 91.7% of the total
      sorption of tomato bulk cuticle.

PMID- 18062421
TI  - Intraspecific differences in effects of co-contamination of cadmium and arsenate
      on early seedling growth and metal uptake by wheat.
AB  - A hydroponic experiment was carried out to study intraspecific differences in the
      effects of different concentrations of cadmium (Cd) (0-10 mg/L) and arsenate
      (As(V)) (0-8 mg/L) on the growth parameters and accumulation of Cd and As in six
      wheat varieties Jing-9428, Duokang-1, Jingdong-11, Jing-411, Jingdong-8 and
      Zhongmai-8. The endpoints of wheat seedlings, including seed germination,
      biomass, root length and shoot height, decreased with increasing the Cd and As
      concentrations. Significant differences in seed germination, biomass, root
      length, shoot height and the accumulation of Cd and As were observed between the
      treatments and among the varieties (p < 0.05). The lethal dosage 50% were about
      20, 80, 60, 60, 80 and 20 mg As/L for Jing-9428, Duokang-1, Jingdong-11, Jing
      411, Jingdong-8 and Zhongmai-8, respectively, and the corresponding values for Cd
      were about 30, 80, 20, 40, 60 and 10 mg Cd/L, respectively. Among the six
      varieties, Duokang-1 was found to be the most resistant to Cd and As toxicity,
      and Zhongmai-8 was the most sensitive to Cd and As co-contamination. The
      resistance of the six varieties was found dependant on the seedling uptake of Cd
      and As. Duokang-1 was the most suitable for cultivation in Cd and As co
      contaminated soils.

PMID- 18062422
TI  - Effects of vegetation type on soil microbial community structure and catabolic
      diversity assessed by polyphasic methods in North China.
AB  - Soil microbes play a major role in ecological processes and are closely
      associated with the aboveground plant community. In order to understand the
      effects of vegetation type on the characteristics of soil microbial communities,
      the soil microbial communities were assessed by plate counts, phospholipid fatty
      acid (PLFA) and Biolog microplate techniques in five plant communities, i.e.,
      soybean field (SF), artificial turf (AT), artificial shrub (AS), natural shrub
      (NS), and maize field (MF) in Jinan, Shandong Province, North China. The results
      showed that plant diversity had little discernible effect on microbial biomass
      but a positive impact on the evenness of utilized substrates in Biolog
      microplate. Legumes could significantly enhance the number of cultural
      microorganisms, microbial biomass, and community catabolic diversity. Except for
      SF dominated by legumes, the biomass of fungi and the catabolic diversity of
      microbial community were higher in less disturbed soil beneath NS than in
      frequently disturbed soils beneath the other vegetation types. These results
      confirmed that high number of plant species, legumes, and natural vegetation
      types tend to support soil microbial communities with higher function. The
      present study also found a significant correlation between the number of cultured
      bacteria and catabolic diversity of the bacterial community. Different research
      methods led to varied results in this study. The combination of several
      approaches is recommended for accurately describing the characteristics of
      microbial communities in many respects.

PMID- 18062423
TI  - Effect of copper on the degradation of pesticides cypermethrin and cyhalothrin.
AB  - The influence of coexisting copper (Cu) ion on the degradation of pesticides
      pyrethroid cypermethrin and cyhalothrin in soil and photodegradation in water
      system were studied. Serial concentrations of the pesticides with the addition of
      copper ion were spiked in the soil and incubated for a regular period of time,
      the analysis of the extracts from the soil was carried out using gas
      chromatography (GC). The photodegradation of pyrethroids in water system was
      conducted under UV irradiation. The effect of Cu2+ on the pesticides degradation
      was measured with half life (t0.5) of degradation. It was found that a negative
      correlation between the degradation of the pyrethroid pesticides in soil and Cu
      addition was observed. But Cu2+ could accelerate photodegradation of the
      pyrethroids in water. The t0.5 for cyhalothrin extended from 6.7 to 6.8 d while
      for cypermethrin extended from 8.1 to 10.9 d with the presence of copper ion in
      soil. As for photodegradation, t0.5 for cyhalothrin reduced from 173.3 to 115.5
      min and for cypermethrin from 115.5 to 99.0 min. The results suggested that
      copper influenced the degradation of the pesticides in soil by affecting the
      activity of microorganisms. However, it had catalyst tendency for
      photodegradation in water system. The difference for the degradation efficiency
      of pyrethroid isomers in soil was also observed. Copper could obviously
      accelerate the degradation of some special isomers.

PMID- 18062424
TI  - Role of the reduction site in the fluorinated or sulfated TiO2 photocatalytic
      process.
AB  - In this article, the effects of TiO2 surface fluorination and sulfation, on the
      active oxygen species formed at the reduction site in the photocatalytic process,
      namely O2*- and H2O2, were investigated from a new perspective. The superoxide
      radical, (O2*-), was determined by colorimetry of nitroblue tetrazolium, a
      prominent O2*- scavenger. Hydrogen peroxide (H2O2) was estimated by using the
      iodide-starch method. In the naked TiO2 photocatalysis, O2*-, though less
      reactive, was a very important intermediate. When the TiO2 surface was
      fluorinated, more O2*- and H2O2 were produced, which indicated that the surface
      modification could greatly reduce the recombination of photogenerated electrons
      and holes, thus enhancing the photocatalytic rate. In the sulfated system,
      photocatalysis proceeded with a more complicated mechanism. These results added
      support to the view of fluoride-induced enhancement and sulfide's nonappreciable
      inhibition effect.

PMID- 18062425
TI  - Arsenic uptake by arbuscular mycorrhizal maize (Zea mays L.) grown in an arsenic
      contaminated soil with added phosphorus.
AB  - The effects of arbuscular mycorrhizal (AM) fungus (Glomus mosseae) and phosphorus
      (P) addition (100 mg/kg soil) on arsenic (As) uptake by maize plants (Zea mays
      L.) from an As-contaminated soil were examined in a glasshouse experiment. Non
      mycorrhizal and zero-P addition controls were included. Plant biomass and
      concentrations and uptake of As, P, and other nutrients, AM colonization, root
      lengths, and hyphal length densities were determined. The results indicated that
      addition of P significantly inhibited root colonization and development of
      extraradical mycelium. Root length and dry weight both increased markedly with
      mycorrhizal colonization under the zero-P treatments, but shoot and root biomass
      of AM plants was depressed by P application. AM fungal inoculation decreased
      shoot As concentrations when no P was added, and shoot and root As concentrations
      of AM plants increased 2.6 and 1.4 times with P addition, respectively. Shoot and
      root uptake of P, Mn, Cu, and Zn increased, but shoot Fe uptake decreased by
      44.6%, with inoculation, when P was added. P addition reduced shoot P, Fe, Mn,
      Cu, and Zn uptake of AM plants, but increased root Fe and Mn uptake of the
      nonmycorrhizal ones. AM colonization therefore appeared to enhance plant
      tolerance to As in low P soil, and have some potential for the phytostabilization
      of As-contaminated soil, however, P application may introduce additional
      environmental risk by increasing soil As mobility.

PMID- 18062426
TI  - Anoxic biodegradation of dimethyl phthalate (DMP) by activated sludge cultures
      under nitrate-reducing conditions.
AB  - Worldwide extensive use of plasticized plastics has resulted in phthalates
      pollution in different environment. Nitrates from industry and agriculture are
      also widely disseminated in the soils, natural waters and wastewaters. Dimethyl
      phthalate (DMP) biodegradation by activated sludge cultures under nitrate
      reducing conditions was investigated. Under one optimized condition, DMP was
      biodegraded from 102.20 mg/L to undetectable level in 56 h under anoxic
      conditions and its reaction fitted well with the first-order kinetics. Using the
      high-performance liquid chromatography (HPLC) and liquid chromatography mass
      spectrometry (LC-MS) analysis, mono-methyl phthalate (MMP) and phthalic acid (PA)
      were detected as the major intermediates of DMP biodegradation. When combined
      with the determination of chemical oxygen demand (COD(Cr)) removal capacity and
      pH, DMP was found to be mineralized completely under anoxic conditions. The
      biodegradation pathway was proposed as DMP -->MMP-->PA-->...-->CO2 + H2O. The
      molar ratio ofDMP to nitrate consumed was found to be 9.0:1, which agrees well
      with the theoretical stoichiometric values of DMP biodegradation by nitrate
      reducing bacteria. The results of the non-linear simulation showed that the
      optimum pH and temperature for the degradation were 7.56 and 31.4 degrees C,
      respectively.

PMID- 18062427
TI  - Biodegradation of methyl parathion by Acinetobacter radioresistens USTB-04.
AB  - Biodegradation of methyl parathion (MP), a widely used organophosphorus
      pesticide, was investigated using a newly isolated bacterium strain Acinetobacter
      radioresistens USTB-04. MP at an initial concentration of 1200 mg/L could be
      totally biodegraded by A. radioresistens USTB-04 as the sole carbon source less
      than 4 d in the presence of phosphate and urea as phosphorus and nitrogen
      sources, respectively. Biodegradation of MP was also achieved using cell-free
      extract of A. radioresistens USTB-04. MP at an initial concentration of 130 mg/L
      was completely biodegraded in 2 h in the presence of cell-free extract with a
      protein concentration of 148.0 mg/L, which was increased with the increase of pH
      from 5.0 to 8.0. Contrary to published reports, no intermediate or final
      degradation metabolites of MP could be observed. Thus we suggest that the
      cleavage of C-C bond on the benzene ring other than P-O bond may be the
      biodegradation pathway of MP by A. radioresistens USTB-04.

PMID- 18062428
TI  - On-line enrichment and determination of polycyclic aromatic hydrocarbons in
      atmospheric particulates using high performance liquid chromatography with
      fluorescence as detector.
AB  - Seven polycyclic aromatic hydrocarbons (PAHs) in atmospheric particulates were
      determinated by high performance liquid chromatography (HPLC) with fluorescence
      detector using direction injection and an on-line enrichment trap column. The
      method simplified the sample pretreatment, saved time and increased the
      efficiency. With the on-line trap column, PAHs were separated availably even
      underground injecting 1.0 ml sample with relatively high column efficiency. The
      recoveries of the seven PAHs were from 85% to 120% for spiked atmospheric
      particulate sample. The limit of detection was 15.3-39.6 ng/L (S/N=3.3). There
      were good linear correlations between the peak areas and concentrations of the
      seven kinds of PAHs in the range of 1-50 ng/ml with the correlation coefficients
      over 0.9970. Furthermore, it also indicated that the method is available to
      determine PAHs in atmospheric particulates well.

PMID- 18062429
TI  - Application of multiwalled carbon nanotubes treated by potassium permanganate for
      determination of trace cadmium prior to flame atomic absorption spectrometry.
AB  - In this study we investigated the enrichment ability of oxidized multiwalled
      carbon nanotubes (MWCNTs) and established a new method for the determination of
      trace cadmium in environment with flame atomic absorption spectrometry. The
      MWCNTs were oxidized by potassium permanganate under appropriate conditions
      before use as preconcentration packing. Parameters influencing the recoveries of
      target analytes were optimized. Under optimal conditions, the target analyte
      exhibited a good linearity (R2=0.9992) over the concentration range 0.5-50 ng/ml.
      The detection limit and precision of the proposed method were 0.15 ng/ml and
      2.06%, respectively. The proposed method was applied to the determination of
      cadmium in real-world environmental samples and the recoveries were in the range
      of 91.3%-108.0%. All these experimental results indicated that this new procedure
      could be applied to the determination of trace cadmium in environmental waters.

PMID- 18062430
TI  - Sensitivity of key factors and uncertainties in health risk assessment of benzene
      pollutant.
AB  - Predicting long-term potential human health risks from contaminants in the
      multimedia environment requires the use of models. However, there is uncertainty
      associated with these predictions of many parameters which can be represented by
      ranges or probability distributions rather than single value. Based on a case
      study with information from an actual site contaminated with benzene, this study
      describes the application of MMSOILS model to predict health risk and
      distributions of those predictions generated using Monte Carlo techniques. A
      sensitivity analysis was performed to evaluate which of the random variables are
      most important in producing the predicted distributions of health risks. The
      sensitivity analysis shows that the predicted distributions can be accurately
      reproduced using a small subset of the random variables. The practical
      implication of this analysis is the ability to distinguish between important
      versus unimportant random variables in terms of their sensitivity to selected
      endpoints. This directly translates into a reduction in data collection and
      modeling effort. It was demonstrated that how correlation coefficient could be
      used to evaluate contributions to overall uncertainty from each parameter. The
      integrated uncertainty analysis shows that although drinking groundwater risk is
      similar with inhalation air risk, uncertainties of total risk come dominantly
      from drinking groundwater route. Most percent of the variance of total risk comes
      from four random variables.

PMID- 18062431
TI  - Quality organizations take center stage. AHIMA active in efforts to improve,
      harmonize quality reporting.

PMID- 18062432
TI  - Privacy in the spotlight.

PMID- 18062433
TI  - HIPAA security redux. A re-evaluation process and recommended areas to review.

PMID- 18062434
TI  - Health data's second life.

PMID- 18062435
TI  - Avoiding the post-implementation blues.

PMID- 18062436
TI  - Aligning the demands for performance data.

PMID- 18062437
TI  - Calculating the costs of E-discovery.

PMID- 18062438
TI  - Confusion continues over HIPAA's minimum necessary standards.

PMID- 18062439
TI  - Breaking down privacy and security barriers to HIE.

PMID- 18062440
TI  - Storing information online. What organizations need to look for in online data
      storage solutions.

PMID- 18062441
TI  - Planning for present on admission.

PMID- 18062442
TI  - Ensuring proper wound care service coding. OIG highlights need for organizations
      to assess wound care coding practices.

PMID- 18062443
TI  - The final rule for FY 2008 IPPS. MS-DRGs and POA top list in a year of major
      change.

PMID- 18062444
TI  - A voice in the future. HIM director takes HIM seat in HIE discussions.

PMID- 18062445
TI  - Excessive sleepiness in Parkinson's disease: a wake-up call.

PMID- 18062446
TI  - Adjuvant chemotherapy for adults with malignant glioma: a systematic review.
AB  - OBJECTIVE: This systematic review examines the role of chemotherapy following
      surgery and external beam radiotherapy for adults with newly diagnosed malignant
      glioma. METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were
      searched to August 2006 to identify relevant randomized controlled trials (RCTs)
      and meta-analyses. Proceedings from the 1997 to 2006 annual meetings of the
      American Society of Clinical Oncology were also searched. RESULTS: Two RCTs
      reported a survival advantage in favour of radiotherapy with concomitant and
      adjuvant temozolomide compared with radiotherapy alone in patients with
      anaplastic astrocytoma or glioblastoma. Twenty-six RCTs and two meta-analyses
      detected either no advantage or a small survival advantage in favour of adjuvant
      chemotherapy. CONCLUSION: Concomitant temozolomide during radiotherapy and post
      radiation adjuvant temozolomide is recommended for all patients ages 18-70 with
      newly diagnosed glioblastoma multiforme who are fit for radical therapy (ECOG 0
      1). Temozolomide may be considered in other situations (i.e., ECOG 2, biopsy
      only, age > 70, intermediate grade glioma), but there is no high-level evidence
      to support this decision. Moreover, there are few data on long-term toxicities or
      quality of life with temozolomide. Adjuvant chemotherapy may be an option for
      younger patients with anaplastic (grade 3) astrocytoma and patients with pure or
      mixed oligodendroglioma. However, there is no evidence of a survival advantage
      from adjuvant chemotherapy in these patients, and treatment-related adverse
      effects and their impact upon quality of life are poorly studied. The combination
      of procarbazine, lomustine, and vincristine (PCV) is not recommended for patients
      with anaplastic oligodendroglioma and oligoastrocytoma.

PMID- 18062447
TI  - A case-control study of tissue plasminogen activator for acute ischemic stroke.
AB  - BACKGROUND: Randomized trials demonstrate that intravenous tissue plasminogen
      activator (tPA) improves outcome in acute ischemic stroke (AIS). To assess
      translation of this efficacy into effectiveness in routine clinical practice we
      performed a case-control study of tPA treatment for AIS in a single hospital.
      METHODS: 151 tPA-treated AIS patients (1996-2005) were matched 1:1 with blinding
      to outcome to controls from a prospective registry based on age, gender, pre
      stroke Oxford handicap scale (OHS), stroke severity, and subtype. The outcomes
      were in-hospital death, symptomatic intracranial hemorrhage (SICH), length-of
      stay (LOS), discharge OHS and long-term survival. RESULTS: In-hospital mortality
      (23% vs. 24%) or long-term survival (median follow-up of 2 years) was not
      different between cases and controls (p = 0.83). SICH occurred in 7.8% (95% CI
      4.2-13.5%) of tPA-treated patients. Median LOS was non-significantly shorter for
      cases (13 [7-29] vs. 16 [8-32] days, p = 0.14) but significantly shorter in tPA
      treated vs. non-treated women (14 [7-28] vs. 20 [11-34] days, p = 0.04). At
      discharge 6.6% (95% CI 1.1-12.0%) more tPA-treated patients than controls had no
      disability (OHS < or = 1, p = 0.02). However, there was no difference in
      discharge independence rates or proportion discharged home. CONCLUSION: We
      demonstrate minor improvements in early recovery after stroke with tPA but the
      impact is less dramatic than that reported in randomized trials. This may relate
      to timing of treatment and the type of patients treated.

PMID- 18062448
TI  - Myocardial infarction following t-PA for acute stroke.
AB  - BACKGROUND AND PURPOSE: Complications of intravenous (IV) thrombolysis with
      tissue plasminogen activator (t-PA) for acute stroke are commonly related to
      hemorrhage, anaphylaxis, or arterial re-occlusion. Embolic complications of t-PA
      are beginning to be recognized with increased use of t-PA for acute ischemic
      stroke. We hypothesize that disruption of intra-cardiac thrombus may result in
      myocardial infarction (MI) after use of t-PA for acute ischemic stroke. SUMMARY
      OF CASES: We describe three cases of acute MI immediately following IV t-PA
      infusion for acute stroke. In patient #1 apical thrombus was visualized on
      cardiac echocardiogram accounting for the MI after t-PA for acute stroke. Patient
      #2 had fresh thrombus seen on cardiac catherization after use of t-PA for acute
      stroke. Patient #3 developed a significant troponin rise 15 hours after the t-PA
      for stroke infusion with an echocardiogram revealing new wall motion
      abnormalities. Patient # 1 and #2 died secondary to multi-organ failure.
      DISCUSSION: Acute MI immediately following t-PA treatment for stroke is a rare
      but serious complication. The disruption of intra-cardiac thrombus and subsequent
      embolization to the coronary arteries may be an important mechanism in the
      development of MI after t-PA treatment for acute ischemic stroke.

PMID- 18062449
TI  - A novel GDAP1 mutation P78L responsible for CMT4A disease in three Moroccan
      families.
AB  - BACKGROUND: The gene encoding the ganglioside-induced-differentiation-associated
      protein 1 (GDAP1) has been associated with both axonal and demyelinating
      neuropathy. Up to date, 25 mutations in the GDAP1 gene have been reported in
      patients from different origins. METHODS: Three Moroccan families with early
      onset ARCMT1 and autosomal recessive inheritance were genotyped to test linkage
      to 8q21.3 and their GDAP1 gene coding exons screened for mutations. RESULTS: A
      novel C233T transversion at codon 78 (P78L) was detected in 6 patients from 3
      unrelated families. The mutation was found to be homozygous in two families and
      compound heterozygous in association with the already reported S194X mutation in
      one family. The P78L mutation was associated with a common haplotype suggesting a
      Moroccan founder mutation. The patients had symptoms within the two first years
      of life and developed common phenotype of CMT4A with evident hoarse-voice in two
      cases with the longer disease duration. CONCLUSION: P78L mutation was associated
      with a common haplotype suggesting a common ancestor.

PMID- 18062450
TI  - Neuromuscular function in survivors of the acute respiratory distress syndrome.
AB  - BACKGROUND: Survivors of acute respiratory distress syndrome (ARDS) report
      generalized weakness and reduced exercise tolerance up to two years following
      discharge from the intensive care unit (ICU). Persistent neuromuscular
      complications of ARDS may contribute to the functional disability observed in
      these patients. METHODS: Sixteen ARDS survivors underwent comprehensive
      neurological evaluation and standardized electrodiagnostic testing 6 to 24 months
      after ICU discharge. Four of these patients agreed to open muscle biopsy.
      RESULTS: Seven of sixteen patients had clinically significant focal compressive
      mononeuropathies. Electrodiagnostic testing failed to reveal any changes
      attributable to critical illness polyneuropathy or myopathy. All four muscle
      biopsies were abnormal, and although the pathological features were structurally
      non-specific, the presence of an acquired myopathy remains possible. Four
      patients had persistent mixed sensory complaints but had normal electrodiagnostic
      evaluation. CONCLUSIONS: The high frequency of mononeuropathies highlights the
      need for vigilance in daily ICU care. The findings also suggest that complaints
      of weakness and reduced exercise capacity in ARDS survivors may be related to
      combined effects of compressive neuropathies and generalized longstanding
      structural changes in muscle and may support an organic basis for long-term
      functional disability.

PMID- 18062451
TI  - Reliability of visual temporal thresholds.
AB  - BACKGROUND: Visual processing deficits involving temporal characteristics are
      typically not captured by the widely used outcome measures (i.e., Expanded
      Disability Status Scale, Multiple Sclerosis Functional Composite) in multiple
      sclerosis (MS). Visual temporal thresholds (i.e., measurements of the temporal
      aspects in visual processing) are typically significantly higher (i.e.,
      prolonged) in MS patients when compared to controls. The test-retest reliability
      of these thresholds was examined in patients with MS. METHODS: Visual temporal
      thresholds were measured in 21 stable MS patients during two separate test
      sessions. Test-retest reliability and the standard error of measurement were
      calculated. The threshold of change in visual temporal thresholds in MS patients
      that would correspond to real change beyond measurement error with 95% certainty
      was also calculated. For comparisons, a control group (n = 10) was included.
      RESULTS: The test-retest reliability of this measure of visual temporal
      thresholds was 0.97. The threshold indicating change beyond chance or measurement
      error with 95% certainty was 11 ms. Higher thresholds were significantly
      correlated with longer durations of disease. CONCLUSIONS: This measure of visual
      temporal thresholds has excellent test-retest reliability and a change of greater
      than 11 ms is highly likely to represent real change in MS patients. The findings
      indicate that these measurements may provide useful clinical information about
      functional changes regarding the temporal aspects of the visual system, which is
      currently not captured by the Extended Disability Status Scale.

PMID- 18062452
TI  - Clinical practice regarding dopamine-agonist use and driving in Parkinson's
      disease.
AB  - BACKGROUND: Current Health Canada instructions for use of the dopamine agonists
      (DA), pramipexole and ropinirole, state that Parkinson's disease (PD) patients
      should be told not to drive. The objective was to assess neurologists' actual
      clinical practice concerning driving advice they give to PD patients starting a
      DA. METHODS: An online survey was created consisting of 4 items regarding
      demographics, 5 regarding PD and driving, and 9 regarding DA use and driving. The
      survey was distributed to 563 neurologists. RESULTS: In total 96 neurologists
      (17.9%) responded. 4.4% tell patients with PD not to drive, solely because they
      are taking a DA. Respondents assess the patient's tendency for excessive daytime
      sleepiness and sleep attacks after starting a DA more frequently than after
      starting other dopaminergic drugs (p < 0.001). DISCUSSION: A minor proportion of
      the clinicians responding to our survey advise PD patients not to drive, solely
      because they use a DA. Such being the case, we propose that current Health Canada
      guidelines need revision.

PMID- 18062453
TI  - PLEDs: clinical correlates.
AB  - OBJECTIVE: We reviewed our experience in 96 consecutive patients exhibiting
      periodic lateralized epileptiform discharges (PLEDs) on EEG. METHODS: EEG reports
      from January 1, 1999 to September 30, 2006 were screened for the term 'PLEDs' and
      its variants. A retrospective chart review, including examination of neuroimaging
      and other investigations, was conducted on each patient identified. RESULTS:
      Acute stroke, tumor and central nervous system infection were the most common
      etiologies, accounting for 26%, 12% and 12% of cases respectively. Acute
      hemorrhage and traumatic brain injury combined accounted for another 12%.
      Previously unreported etiologies included posterior reversible encephalopathy
      syndrome (PRES), familial hemiplegic migraine and cerebral amyloidosis. There
      were 9 cases of chronic PLEDs attributable to underlying cortical dysplasia or
      severe remote cerebral injury, all with an accompanying partial seizure disorder.
      A prominent role for alcohol withdrawal was noted, and in 6 cases was the sole
      etiological factor. Fever was present as a potential contributing factor in 40%
      of cases, and significant metabolic abnormalities in 35%. Seizure activity
      occurred in 85% of patients overall, but in 100% of patients with PLEDs Plus and
      BiPLEDs Plus. The overall mortality rate was 27%. Mortality among patients with
      BiPLEDs however was almost twice that, at 52%. CONCLUSIONS: This case series
      demonstrates the wide variety of potential PLED etiologies. It also emphasizes
      that despite advances in neurocritical care, the morbidity and mortality
      associated with PLEDs has changed little since their recognition four decades
      ago.

PMID- 18062454
TI  - Histopathological examination of intervertebral disc specimens: a cost-benefit
      analysis.
AB  - OBJECT: Routine histopathological examination of intervertebral disc specimens is
      commonly performed in North American hospitals, but recent studies have
      questioned the utility of this practice in cases where the indication for surgery
      is a benign process such as degenerative disc disease. In this study, we have
      performed a cost-benefit analysis of this practice. METHODS: We performed a cost
      benefit analysis of routine histopathological examination of 1775 routine (non
      neoplastic and non-infectious indications for surgery) and 70 non-routine
      (suspected neoplastic or infectious indications for surgery) discectomy specimens
      obtained over an eight-year period (1996 and 2004). Chart reviews were used to
      determine if any histopathology findings were clinically significant (i.e.,
      affected subsequent patient care). Total costs were calculated. A literature
      review was conducted to compare our results with other published series. RESULTS:
      We found four unexpected histopathology results among 1775 specimens obtained
      from routine cases, one of which was clinically significant. We calculated costs
      of $42,165.25 per unexpected histopathological finding and $168,625 per
      clinically significant histopathological finding. For non-routine surgeries, the
      cost per abnormal pathological finding was $116.67. CONCLUSIONS: In routine
      cases, histopathological examination of disc specimens is not justified. The
      decision to send specimens for pathological examination should be based on the
      surgeon's judgment.

PMID- 18062455
TI  - Occipital condyle syndrome as the first sign of metastatic cancer.
AB  - BACKGROUND: Occipital condyle syndrome is characterized by severe, unilateral,
      occipital headache and ipsilateral twelfth-nerve palsy. It is associated with
      skull-base metastasis. CASES: We identified two patients with sub-acute onset of
      severe, unilateral, occipital headache and ipsilateral tongue paralysis. The
      first patient was a 58-year-old woman with a history of limited stage small-cell
      lung cancer in clinical remission. The second patient was an otherwise healthy 36
      year-old man. Neither patient had any other findings on general medical or
      neurological examination. One patient had only equivocal findings on initial
      magnetic resonance imaging (MRI), and the other patient's MRI was normal.
      Although initial work-up for metastatic disease was normal, the first patient
      developed severe bone pain over the next few months, and follow-up investigations
      demonstrated metastases to her spine, tibia, skull base and brain. The second
      patient improved initially, but was admitted to hospital three months later with
      constitutional symptoms and pancytopenia. Bone marrow and lymph node biopsies
      were consistent with Stage IVB Hodgkin's lymphoma. CONCLUSION: Occipital condyle
      syndrome can be the first presentation of disseminated malignancy. Initial
      imaging of the brain and skull base may be normal, and recognition of this
      syndrome warrants thorough investigation and close follow-up.

PMID- 18062456
TI  - Endovascular management of an embedded intracranial knife.
AB  - BACKGROUND: Endovascular therapy (ET) is infrequently used in the setting of
      acute penetrating intracranial trauma. METHODS: We report a case where ET was
      used immediately prior to and following removal of an embedded intracranial
      knife, which was found to be disrupting the anterior cerebral artery. RESULTS:
      The proximal vessel was coiled and angiographically occluded and then the knife
      was removed with the microcatheter in place. Immediate angiography allowed us to
      see and quickly treat the contrast extravasation with further coiling. Despite
      full medical management, the patient died of elevated intracranial pressure.
      CONCLUSION: In this severely injured patient, endovascular therapy represented
      the most suitable means to attempt safe removal of the knife.

PMID- 18062457
TI  - Sporadic Creutzfeldt-Jakob disease with worsening depression and cognition.

PMID- 18062458
TI  - Reversible cerebral vasoconstriction syndrome or primary angiitis of the central
      nervous system?
AB  - BACKGROUND: Reversible Cerebral Vasoconstriction Syndrome (RCVS) may present as
      thunderclap headache (TCH), accompanied by reversible cerebral vasospasm and
      focal neurological deficits, often without a clear precipitant. RCVS may be
      mistaken for Primary Angiitis of the Central Nervous System (PACNS) due to the
      presence of similar angiographic features of segmental narrowing of cerebral
      arteries. We discuss the clinical features of a young female migraine patient who
      developed TCH and was found to have RCVS following initial treatment with
      corticosteroids for PACNS, in the context of a systematic review of the available
      medical literature. METHODS: A Medline search was performed to identify all case
      reports since 1966 describing RCVS and PACNS that provide sufficient clinical
      detail to permit diagnostic classification according to published criteria. RCVS
      included case studies in which there was angiographic or transcranial Doppler
      ultrasound evidence of near-to-complete resolution of cerebral vasoconstriction
      in the absence of a well-recognized secondary cause. PACNS included reports of
      histologically confirmed PACNS either through biopsy or necropsy. RESULTS:
      Reversible Cerebral Vasoconstriction Syndrome occurs primarily in females and is
      characterized by sudden, severe headache at onset, normal CSF analysis,
      vasoconstriction involving the Circle of Willis and its immediate branches, and
      angiographic or TCD ultrasound evidence of near-to-complete vasospastic
      resolution within 1-4 weeks. It occurs typically in the context of
      vasoconstrictive drug use, the peripartum period, bathing, and physical exertion.
      CONCLUSION: Initial and follow-up (within 4 weeks) non-invasive angiographic
      studies are indicated in patients who present with TCH or who have clinical
      presentations that could be consistent with RCVS or PACNS in the absence of a
      well-recognized secondary cause, such as subarachnoid haemorrhage. Early
      reversibility of cerebral vasospasm is the key neuroradiological feature that
      supports the clinical diagnosis of RCVS.

PMID- 18062459
TI  - Salivary gland-like tumor of the sella.

PMID- 18062460
TI  - Remote cerebellar haemorrhage after spinal surgery.

PMID- 18062461
TI  - Bowel injury following lumbar discectomy using minimally invasive retractors.

PMID- 18062462
TI  - Spontaneous spinal epidural hematoma in a child with hemophilia B.

PMID- 18062463
TI  - Acute epidural hematoma secondary to skull metastasis from esophageal carcinoma.

PMID- 18062464
TI  - "Eugenics" by another name?

PMID- 18062465
TI  - Re: Whiplash and concussion: similar acute changes in middle-latency SEPs.
      Zumsteg D, Wennberg R, Gutling E, Hess K. Can J Neurol Sci. 2006;33:379-86.

PMID- 18062466
TI  - Migraine treatment.
AB  - The goal of the Canadian Migraine Forum was to work towards improving the lives
      of Canadians with migraine by reducing their migraine-related disability. This
      paper focuses on migraine treatment in its many aspects, including symptomatic
      therapy of individual migraine headache attacks, prophylactic drug therapy, non
      pharmacological interventions, and diagnosis and management of symptomatic
      medication overuse. Many patients with difficult migraine experience significant
      frustration in trying to obtain the help they need from our current medical
      system. Although many symptomatic medications are available for use in migraine,
      migraine specific medications are still underutilized. An ideal migraine
      preventative medication does not yet exist, but currently available preventatives
      do have utility, and are also thought to be underutilized. Behavioral approaches
      to migraine management as an adjunct to medication therapy show promise, but the
      availability of programs to bring these to patients is limited, and more research
      is needed on their efficacy. Symptomatic medication overuse in migraine sufferers
      remains a large problem in Canada, and better defined treatment paradigms and
      programs are needed both to prevent and to treat this problem. Such programs
      should include strong elements of public, patient, and health professional
      education. A potential solution to some of these problems may be to develop
      treatment approaches to migraine similar to those that are being developed for
      other chronic medical disorders. For patients with severe migraine, these would
      optimally include multidisciplinary teams so that the multiple facets of migraine
      management can be adequately addressed.

PMID- 18062467
TI  - Moving forward to improve migraine management in Canada.
AB  - The goal of the Canadian Migraine Forum was to work towards improving the lives
      of Canadians with migraine by reducing their migraine-related disability.
      Migraine has been ranked 19th by the World Health Organization among causes of
      years of life lived with disability. To improve management of migraine in Canada,
      the participants in the forum identified several important needs and strategies.
      There is a need for more leaders in the field of migraine to work with other
      stakeholders to obtain funding and develop treatment programs across Canada.
      Leadership is also required to address the under use of both migraine specific
      symptomatic medications and prophylactic medications in Canada. More non
      physician health professionals are required to work with physicians in migraine
      treatment teams. This could assist with a shortage of physician resources, and
      could also help to better meet the needs of the migraine patient. Individuals
      with migraine need to be identified who could work with health care professionals
      to help meet the needs of the migraine patients in our communities. Application
      of the chronic disease management model for migraine treatment was also seen as
      an important factor for the management of migraine. Programs are needed to
      promote earlier diagnosis, long-term follow-up, comprehensive patient education,
      and the use of multidisciplinary treatment teams where appropriate. Also
      considered important was the need to increase knowledge about migraine through
      public awareness campaigns, websites, medical education, and appropriate reading
      material for patients. The public needs to be aware that migraine is a biological
      disorder that can cause significant disability and suffering. Lastly, there is a
      pressing need to promote more migraine research, including careful outcome
      assessments for treatment programs that involve non-pharmacological treatments
      and a team based approach to migraine management. There are many challenges that
      must be overcome if we are to be successful in reducing migraine related
      disability in Canada. Success will depend upon the joint efforts of physicians,
      other healthcare professionals, individuals with migraine, and the public at
      large.

PMID- 18062468
TI  - Prevalence of white spot syndrome virus (WSSV) in wild shrimp Penaeus monodon in
      the Philippines.
AB  - Prevalence of white spot syndrome virus (WSSV) was determined using polymerase
      chain reaction (PCR) methodology on DNA extracted from the gills of wild black
      tiger shrimp Penaeus monodon collected from 7 sampling sites in the Philippines.
      These 7 sampling sites are the primary sources of spawners and broodstock for
      hatchery use. During the dry season, WSSV was detected in shrimp from all sites
      except Bohol, but during the wet season it was not detected in any site except
      Palawan. None of the WSSV-PCR positive shrimp showed signs of white spots in the
      cuticle. Prevalence of WSSV showed seasonal variations, i.e. prevalence in dry
      season (April to May) was higher than in the wet season (August to October).
      These results suggest that WSSV has already become established in the local
      marine environment and in wild populations of P. monodon. Thus, broodstock
      collected during the dry season could serve as the main source of WSSV
      contamination in shrimp farms due to vertical transmission of the virus in
      hatcheries.

PMID- 18062469
TI  - Phylogenetic analysis of betanodaviruses isolated from cultured fish in Korea.
AB  - Since the publication of the first report on fish nodaviruses in Korea in 1998,
      fish nodaviruses have caused widespread epizootic events among various fish
      species in Korea. However, the genotypes of fish nodaviruses in Korea have not
      yet been determined due to a lack of information about their nucleotide
      sequences. In this study, we isolated 5 fish nodaviruses from 4 fish species
      cultured in 4 different regions in Korea: rock bream Oplegnathus fasciatus,
      Japanese flounder Paralichthys olivaceus, sevenband grouper Epinephelus
      septemfasciatus, and grey mullet Mugil cophalus. The full open-reading frame
      (ORF) encoding the coat protein (1017 nt) was sequenced from each of the 5 fish
      nodaviruses and the nucleotide sequences were phylogenetically analyzed. Results
      showed that even though their sequences were not identical, all 5 Korean isolates
      were clustered in the RGNNV genotype. This is the first report on the
      phylogenetic analysis of fish nodaviruses from cultured fish in Korea.

PMID- 18062470
TI  - Severe mortality in wild Atlantic salmon Salmo salar due to proliferative kidney
      disease (PKD) caused by Tetracapsuloides bryosalmonae (myxozoa).
AB  - Extensive mortality in Atlantic salmon fry was reported in the River Aelva from
      2002 to 2004. Dead fish were collected in late summer 2006, and live fish were
      sampled by electrofishing in September the same year. At autopsy and in
      histological sections, the fish kidneys were found to be pale and considerably
      enlarged. Proliferative lesions with characteristic PKX cells were seen in a
      majority of the fish. DNA from kidney samples of diseased fish was subjected to
      PCR and sequencing, and the amplified sequences matched those of Tetracapsuloides
      bryosalmonae. We concluded that this myxozoan transmitted from bryozoans was the
      main cause of the observed mortality in salmon fry in 2006. Results from
      quantitative electrofishing in 2005 and 2006, combined with the observed fry
      mortality from 2002 to 2004, show that the smolt production in the river is
      severely reduced and that T. bryosalmonae is the most likely explanation for this
      decline. The present study is the first to report a considerable negative
      population effect in wild Atlantic salmon due to proliferative kidney disease
      (PKD). It also represents the northernmost PKD outbreak in wild fish. The river
      is regulated for hydroelectric power purposes, causing reduced water flow and
      elevated summer temperatures, and the present PKD outbreak may serve as an
      example of increased disease vulnerability of northern fish populations in a
      warmer climate.

PMID- 18062471
TI  - Efficacy of orally administered praziquantel against Zeuxapta seriolae and
      Benedenia seriolae (Monogenea) in yellowtail kingfish Seriola lalandi.
AB  - We investigated the efficacy of praziquantel (PZQ) administered orally to
      yellowtail kingfish (Seriola lalandi in sea-cage aquaculture in South Australia)
      against the monogeneans Zeuxapta seriolae and Benedenia seriolae infesting gills
      and skin, respectively. PZQ was administered to fish by surface-coating feed
      pellets (Trial 1) or by direct intubation of the stomach (Trial 2). In both
      trials 4 daily doses were administered: 50 and 75 mg kg(-1) body weight (BW) d(
      1) for 6 d, and 100 and 150 mg kg(-1) BW d(-1) for 3 d. Mean parasite intensity
      was compared between medicated fish and unmedicated control fish. In Trial 1,
      fish fed lower daily doses of PZQ for 6 d (50 and 75 mg kg(-1) BW d(-1)) had
      fewer Z. seriolae and B. seriolae than fish fed higher daily doses for 3 d (100
      and 150 mg kg(-1) BW d(-1)). Fish rejected feed pellets surface-coated with PZQ,
      suggesting PZQ affected palatability of feed, and may explain differences in
      efficacy between treatments. In Trial 2, where PZQ was administered by
      intubation, there were fewer Z. seriolae and B. seriolae in medicated fish than
      control fish. Intubated PZQ was also effective against newly recruited Z.
      seriolae and B. seriolae. PZQ could be developed as a useful treatment for Z.
      seriolae and B. seriolae parasitising S. lalandi in sea-cage aquaculture if
      suspected palatability problems are resolved.

PMID- 18062473
TI  - Ultrastructure of sporulation in Haplosporidium armoricanum.
AB  - An ultrastructural study was carried out on the tissues of an oyster (Ostrea
      edulis), heavily infected with Haplosporidium armoricanum, that had been fixed in
      Carson's fixative. The well-fixed tissues revealed details of sporulation and of
      the spores, which had not been previously reported from H. armoricanum. These
      include the initial presence of sparse haplosporosomes after thickening of the
      plasma membrane in early sporonts, division of sporont nuclei by multiple
      fission, cup-like indentations in the nuclear surface associated with putative
      nuclear material in both the sporonts and spores, and cytoplasmic multi-vesicular
      bodies in the cytoplasm of sporonts and spores. The spore wall and operculum were
      formed from a light matrix that occurred in short cisternae of smooth endoplasmic
      reticulum in the episporoplasm, and parallel bundles of microfibrils were present
      in some spores. Spores were rarely bi-nucleate with the nuclei occurring as a
      diplokaryon, with putative nuclear material at the junction of the 2 nuclei.
      Nuclear membrane-bound Golgi (NM-BG) cisternae were common in spores, and they
      appeared to synthesise a light granular material into lysosome-like granules.
      Dense bodies similar to those reported from H. lusitanicum, H. pickfordi and H.
      monforti occurred in, or outside, the peripheral endosporoplasm, which was
      closely apposed to the spore wall. Spore haplosporosomes were frequently axehead
      shaped, more like those of H. costale than those previously reported from H.
      armoricanum, and in some haplosporosomes there was a small round lucent patch
      with a dark point near the centre of the lucent patch. Overall, H. armoricanum
      appears to be closely related to H. costale and Bonamia spp. Although the
      endosporoplasm of H. armoricanum has NM-BG and it resembles the uni-nucleate
      stage, it appears to be unlikely that they are the same, as the axehead-shaped
      haplosporosomes of the spore differ considerably from the spherical
      haplosporosomes of vegetative stages.

PMID- 18062472
TI  - Pathogens in Crassostrea ariakensis and other Asian oyster species: implications
      for non-native oyster introduction to Chesapeake Bay.
AB  - With the drastic decline of eastern oyster Crassostrea virginica populations in
      the Chesapeake Bay due to over-fishing, diseases and habitat destruction, there
      is interest in Maryland and Virginia in utilizing the non-native oyster species
      Crassostrea ariakensis for aquaculture, fishery resource enhancement, and
      ecological restoration. The International Council for the Exploration of the Sea
      (ICES) recommends that non-native species be examined for ecological, genetic and
      disease relationships in the native range prior to a deliberate introduction to a
      new region. Therefore, a pathogen survey of C. ariakensis and other sympatric
      oyster species was conducted on samples collected in the PR China, Japan and
      Korea using molecular diagnostics and histopathology. Molecular assays focused on
      2 types of pathogens: protistan parasites in the genus Perkinsus and
      herpesviruses, both with known impacts on commercially important molluscan
      species around the world, including Asia. PCR amplification and DNA sequence data
      from the internal transcribed spacer region of the rRNA gene complex revealed the
      presence of 2 Perkinsus species not currently found in USA waters: P. olseni and
      an undescribed species. In addition, 3 genetic strains of molluscan herpesviruses
      were detected in oysters from several potential C. ariakensis broodstock
      acquisition sites in Asia. Viral gametocytic hypertrophy, Chlamydia-like
      organisms, a Steinhausia-like microsporidian, Perkinsus sp., Nematopsis sp.,
      ciliates, and cestodes were also detected by histopathology.

PMID- 18062474
TI  - Phocid seals, seal lice and heartworms: a terrestrial host-parasite system
      conveyed to the marine environment.
AB  - Adaptation of pinnipeds to the marine habitat imposed parallel evolutions in
      their parasites. Ancestral pinnipeds must have harboured sucking lice, which were
      ancestors of the seal louse Echinophthirius horridus. The seal louse is one of
      the few insects that successfully adjusted to the marine environment. Adaptations
      such as keeping an air reservoir and the ability to hold on to and move on the
      host were necessary, as well as an adjustment of their life cycle to fit the
      diving habits of their host. E. horridus are confined to the Northern Hemisphere
      and have been reported from 9 species of northern phocids belonging to 4 genera,
      including land-locked seal species. The transmission from seal to seal is only
      possible when animals are hauled-out on land or ice. Lice are rarely found on
      healthy adult seals, but frequently on weak and young animals. The seal louse is
      suggested to play an important role as an intermediate host transmitting the
      heartworm Acanthocheilonema spirocauda among seals. However, the evidence is
      restricted to a single study where the first 3 larval stages of the heartworm
      were shown to develop in the louse. The fourth-stage larvae develop in the blood
      system of seals and eventually transform into the adult stage that matures in the
      heart. Since all other studies failed to confirm the presence of heartworm larvae
      in seal lice, other unknown intermediate hosts could be involved in the
      transmission of the heartworm. Transplacental transmission of microfilariae in
      seals has been suggested as an additional possibility, but is not likely to be
      important since the occurrence of heartworms in adult seals is very rare compared
      with juveniles. Furthermore, there are no findings of the first 3 larval stages
      in seals. This review shows that the heartworm infects nearly the same species of
      seals as the seal louse, except for the grey seal Halichoerus grypus, where the
      heartworm is absent. Prevalence and intensity of infection differ among regions
      in the Northern Hemisphere. As for seal lice, heartworms mainly infect immature
      seals, and after infection the prevalence seems to decrease with increasing age
      of the host.

PMID- 18062475
TI  - Myxobolus sp. can cause in vivo myoliquefaction in the host Paralichthys
      orbignyanus (Osteichthyes, Paralichthydae).
AB  - We found intense myoliquefaction in vivo among specimens of wild and farmed South
      American flatfish Paralichthys orbignyanus Valenciennes, 1839. The soft flesh
      condition was attributed to Myxobolus sp. since the fish were not infected by
      myxosporeans which are usually associated with this condition (Kudoa spp.), and
      other causes (bacteria, fungi) were not found. The histopathology of the
      infection is described.

PMID- 18062476
TI  - Environmental impact of aquaculture and countermeasures to aquaculture pollution
      in China.
AB  - GOAL, SCOPE AND BACKGROUND: Aquaculture activities are well known to be the major
      contributor to the increasing level of organic waste and toxic compound in the
      aquaculture industry. Along with the development of intensive aquaculture in
      China, concerns are evoked about the possible effects of ever-increasing
      aquaculture waste both on productivity inside the aquaculture system and on the
      ambient aquatic ecosystem. Therefore, it is apparent that appropriate waste
      treatment processes are needed for sustaining aquaculture development. This
      review aims at identifying the current status of aquaculture and aquaculture
      waste production in China. MAIN FEATURES: China is the world's largest fishery
      nation in terms of total seafood production volume, a position it has maintained
      continuously since 1990. Freshwater aquaculture is a major part of the Chinese
      fishery industry. Marine aquaculture in China consists of both land-based and
      offshore aquaculture, with the latter mostly operated in shallow seas, mud flats
      and protected bays. The environmental impacts of aquaculture are also striking.
      RESULTS: Case studies on pollution hot spots caused by aquaculture have been
      introduced. The quality and quantity of waste from aquaculture depends mainly on
      culture system characteristics and the choice of species, but also on feed
      quality and management. Wastewater without treatment, if continuously discharged
      into the aquatic environment, could result in remarkable elevation of the total
      organic matter contents and cause considerable economy lost. Waste treatments can
      be mainly classified into three categories: physical, chemical and biological
      methods. DISCUSSION: The environmental impacts of different aquaculture species
      are not the same. New waste treatments are introduced as references for the
      potential development of the waste treatment system in China. The most
      appropriate waste treatment system for each site should be selected according to
      the sites' conditions and financial status as well as by weighing the advantages
      and disadvantages of each system. Strategies and perspectives for sustainable
      aquaculture development are proposed, with the emphasis on environmental
      protection. CONCLUSIONS: Negative effects of waste from aquaculture to aquatic
      environment are increasingly recognized, though they were just a small proportion
      to land-based pollutants. Properly planned use of aquaculture waste alleviates
      water pollution problems and not only conserves valuable water resources but also
      takes advantage of the nutrients contained in effluent. It is highly demanding to
      develop sustainable aquaculture which keeps stocking density and pollution
      loadings under environmental capacity. RECOMMENDATIONS AND PERSPECTIVES: The
      traditional procedures for aquaculture waste treatment, mainly based on physical
      and chemical means, should be overcome by more site-specific approaches, taking
      into account the characteristics and resistibility of the aquatic environment.
      Further research needs to improve or optimize the current methods of wastewater
      treatment and reuse. Proposed new treatment technology should evaluate their
      feasibility at a larger scale for practical application.

PMID- 18062477
TI  - Management of marine cage aquaculture. Environmental carrying capacity method
      based on dry feed conversion rate.
AB  - GOAL, SCOPE AND BACKGROUND: Marine cage aquaculture produces a large amount of
      waste that is released directly into the environment. To effectively manage the
      mariculture environment, it is important to determine the carrying capacity of an
      aquaculture area. In many Asian countries trash fish is dominantly used in marine
      cage aquaculture, which contains more water than pellet feed. The traditional
      nutrient loading analysis is for pellet feed not for trash fish feed. So, a more
      critical analysis is necessary in trash fish feed culturing areas. METHODS:
      Corresponding to FCR (feed conversion rate), dry feed conversion rate (DFCR) was
      used to analyze the nutrient loadings from marine cage aquaculture where trash
      fish is used. Based on the hydrodynamic model and the mass transport model in
      Xiangshan Harbor, the relationship between the water quality and the waste
      discharged from cage aquaculture has been determined. The environmental carrying
      capacity of the aquaculture sea area was calculated by applying the models noted
      above. RESULTS: Nitrogen and phosphorus are the water quality parameters
      considered in this study. The simulated results show that the maximum nitrogen
      and phosphorus concentrations were 0.216 mg/L and 0.039 mg/L, respectively. In
      most of the sea area, the nutrient concentrations were higher than the water
      quality standard. The calculated environmental carrying capacity of nitrogen and
      phosphorus in Xiangshan Harbor were 1,107.37 t/yr and 134.35 t/yr, respectively.
      The waste generated from cage culturing in 2000 has already exceeded the
      environmental carrying capacity. DISCUSSION: Unconsumed feed has been identified
      as the most important origin of all pollutants in cage culturing systems. It
      suggests the importance of increasing the feed utilization and improving the feed
      composition on the basis of nutrient requirement. For the sustainable development
      of the aquaculture industry, it is an effective management measure to keep the
      stocking density and pollution loadings below the environmental carrying
      capacity. CONCLUSIONS: The DFCR-based nutrient loadings analysis indicates, in
      trash fish feed culturing areas, that it is more critical and has been proved to
      be a valuable loading calculation method. The modeling approach for Xiangshan
      Harbor presented in this paper is a cost-effective method for assessing the
      environmental impact and determining the capacity. Carrying capacity information
      can give scientific suggestions for the sustainable management of aquaculture
      environments. RECOMMENDATIONS AND PERSPECTIVES: It has been proved that numerical
      models were convenient tools to predict the environmental carrying capacity. The
      development of models coupled with dynamic and aquaculture ecology is a
      requirement of further research. Such models can also be useful in monitoring the
      ecological impacts caused by mariculture activities.

PMID- 18062478
TI  - Bioremediation process on Brazil shoreline. Laboratory experiments.
AB  - GOAL, SCOPE AND BACKGROUND: Bioremediation technique can be considered a
      promising alternative to clean oil spills using microbial processes to reduce the
      concentration and/or the toxicity of pollutants. To understand the importance of
      this work we must know that there is only little research performed to date using
      bioremediation techniques to clean oil spills in tropical countries. So, the main
      objective of this work is to analyze the behavior of a laboratory's
      bioremediation test using nutrients on coastal sediments. METHODS: The
      bioremediation process is followed through geochemical analysis during the tests.
      This organic material is analyzed by medium pressure liquid chromatography
      (MPLC), gas chromatography/flame ionization detection (GC/FID) and gas
      chromatography/ mass spectrometry. By microbial counting, the number of total
      bacteria and degrading bacteria is determined during the experiments, in order to
      confirm the effectiveness of the bioremediation process. The seawater obtained
      throughout the bioremediation process is analyzed for nutrients grade (phosphate
      and ammonium ions) and also for its toxicity (Microtox tests) due the presence of
      hydrocarbons and fertilizer. RESULTS: The results from the geochemical analyses
      of the oil show a relative decrease in the saturated hydrocarbon fraction that is
      compensated by a relative enrichment on polar compounds. It's confirmed by the
      fingerprint evaluation where it is possible to see a complete reduction of the
      normal alkanes followed by isoprenoids. Seawater analysis done by toxicity and
      nutrients analysis, such as microbial counting (total and degrading bacteria),
      confirm the fertilizer effectiveness during the bioremediation process.
      DISCUSSION: Results from simulating test using NPK, a low-price plant fertilizer,
      suggest that it's able to stimulate the degradation process. Results from medium
      pressure liquid chromatography (MPLC), done at two different depths (surface and
      subsurface), show different behavior during the biodegradation process where the
      later is seen to be more susceptible to microbial attack. Data from
      bioremediation unit shows a bigger reduction of the saturated fraction, followed
      by some smaller reduction of aromatic fractions, compensated by a relative
      increase from polar compounds (NSO). n-C17/pristane, n-C18/ fitane and
      pristane/fitane rates show constant values for the unity control, different from
      bioremediation samples which have a significant reduction, especially on
      subsurface areas, where a strong fall in the rates, seen to be reduced to zero
      over twenty days, had occurred during the first ten days. However, sample
      surfaces are reduced to zero in thirty days of experiments, proving that
      biodegradation is better on subsurfaces. Gaseous chromatography/mass spectrometry
      (CG/MS) analysis shows constant values to cyclic biomarker rates and aromatic
      compounds, suggesting that the biodegradation process is not strong enough to
      reduce these composites. Microbial analysis shows a reduction on heterotrophic
      (total bacteria) number from control unit, probably because the bacteria uses the
      spill oil like carbon source and energy. However, the number increases on
      bioremediation unit, because it uses NPK like a biostimulator. The
      hydrocarbonoclastic number isn't enough on the first moment, but it's detected
      after 30 days and quantified in all units, showing big values especially in
      bioremediation. Toxicity tests confirm that NPK fertilizer does not intoxicate
      the shoreline during the application of the bioremediation technique. Some
      nutrient concentration shows high values of ammonium and phosphate per
      bioremediation unit, reducing by the end of the experiment. CONCLUSIONS: Results
      reached the goal, finding a proper nutrient (NPK fertilizer) to stimulate the
      biodegradation process, growing bacteria responsible for reducing impact
      contaminated coast ambient by oil spills. Chemical analysis of oil shows a
      reduction in the saturated fraction with a relative enrichment in polar
      composites (NSO) and the aromatic fraction from oil remaining constant.
      Subsurface samples show more biodegradation than surface samples, probably
      because the first one has higher humidity. Linear alcanes are more biodegraded
      than isoprenoids, confirming the biodegradation susceptibility order. Saturated
      cyclic biomarkers and aromatic compounds show constant behavior maybe because the
      nutrients or time was not enough for microorganismic attack. Fertilizer does not
      demonstrate any toxic effects in local biota so that it does not compromise the
      technique applicability and the environment is not saturated by nutrients during
      the simulation, especially since the coastal environment is an open system
      affected daily by tides. Therefore, bioremediation tests can be classified as
      moderate, reaching level 5 in the classification scale by Peters & Moldowan
      (1993). RECOMMENDATIONS AND PERSPECTIVES: The use of marine environment by the
      petroleum industry on exploration, production and transportation operation,
      transform this oil to become the most important pollutant in the oceans.
      Bioremediation is an important technique used to clean spilled oil impacting on
      shorelines, accelerating the biodegradation process by using fertilizer growing
      the microorganisms responsible for decontaminating the environment. We recommend
      confirming the efficiency of NPK nutrient used on bioremediation simulating
      experiments on beaches, while monitoring the chemical changes long-term. NPK
      fertilizer can be used to stimulate the biodegradation process on shoreline
      impacted by spilled oil.

PMID- 18062479
TI  - Feasibility assessment of electrocoagulation towards a new sustainable wastewater
      treatment.
AB  - BACKGROUND, AIM AND SCOPE: Electrocoagulation (EC) may be a potential answer to
      environmental problems dealing with water reuse and rational waste management.
      The aim of this research was to assess the feasibility of EC-process for
      industrial contaminated effluents from copper production, taking into
      consideration technical and economical factors. EC-technology claims to offer
      efficient removal rates for most types of wastewater impurities at low power
      consumption and without adding any precipitating agents. MATERIALS AND METHODS:
      Real wastewater from Saraka stream with high concentrations of heavy metals was
      provided by RTB-BOR, a Serbian copper mining and smelting complex. Runs were
      performed on a 10 l EC-reactor using aluminum plates as sacrificial electrodes
      and powered by a 40 A supply unit. Results concerning key factors like pH,
      conductivity and power consumption were measured in real time. Analysis of
      dissolved metal concentrations before and after treatment were carried out via
      ICP-OES and confirmed by an independent test via AAS. RESULTS: Several aspects
      were taken into account, including current density, conductivity, interfacial
      resistivity and reactor settings throughout the runs, in order to analyze all
      possible factors playing a role in neutralization and metal removal in real
      industrial wastewater. DISCUSSION: Electrode configurations and their effects on
      energy demand were discussed and exemplified based on fundamentals of colloidal
      and physical chemistry. CONCLUSIONS: Based on experimental data and since no
      precipitating agents were applied, the EC-process proved to be not only feasible
      and environmentally-friendly, but also a cost-effective technology
      RECOMMENDATIONS AND PERSPECTIVES: The EC-technology provides strategic guidelines
      for further research and development of sustainable water management processes.
      However, additional test series concerning continuous operation must be still
      performed in order to get this concept ready for future large-scale applications.

PMID- 18062480
TI  - Heavy metals in untreated/treated urban effluent and sludge from a biological
      wastewater treatment plant.
AB  - BACKGROUND, AIM AND SCOPE: The presence of heavy metals in wastewater is one of
      the main causes of water and soil pollution. The aim of the present study was to
      investigate the removal of Cd, Cu, Pb, Hg, Mn, Cr and Zn in urban effluent by a
      biological wastewater treatment, as well as to quantify the levels of As, Be, Cd,
      Cr, Cu, Fe, Hg, Mn, Ni, Pb, Sn, Tl, V and Zn in dewatering sludge from the
      Biological Wastewater Treatment Plant of Ribeirao Preto (RPBWTP), Brazil.
      MATERIALS AND METHODS: Concentrations of Cd, Cr, Cu, Mn and Pb in wastewater and
      those of Ni in sludge were determined by atomic absorption spectrophotometry with
      graphite furnace atomization. Mercury concentrations in wastewater were measured
      by hydride generation atomic spectrophotometry, and Zn levels were determined by
      atomic absorption spectrophotometry using acetylene flame. In sludge, the levels
      of As, Be, Cd, Cr, Cu, Fe, Hg, Mn, Pb, Sn, TI, V and Zn were determined by
      inductively coupled plasma-mass spectrometry. Results. The percentages of removal
      efficiency (RE) were the following: Hg 61.5%, Cd 60.0%, Zn 44.9%, Cu 44.2%, Pb
      39.7%, Cr 16,5% and Mn 10.4%. In turn, the mean concentrations (mg/kg) of metals
      in dewatering sludge followed this increasing order: Tl (< 0.03), Hg (0.31), Be
      (0.43), As (1.14), Cd (1.34), V (59.2), Pb (132.1), Sn (166.1), Cr (195.0), Mn
      (208.1), Ni (239.4), Cu (391.7), Zn (864.4) and Fe (20537). DISCUSSION: The
      relationship between metal levels in untreated wastewater, as well as the removal
      efficiency are in agreement with previous data from various investigators. It is
      important to note that metal removal efficiency is not only affected by metal ion
      species and concentration, but also by other conditions such as operating
      parameters, physical, chemical, and biological factors. CONCLUSIONS: Metal values
      recorded for treated wastewater and sludge were within the maximum permitted
      levels established by the Environmental Sanitation Company (CETESB), Sao Paulo,
      Brazil. RECOMMENDATIONS: There is an urgent need for the authorities who are
      responsible for legislation on sludge uses in agriculture of establishing safety
      levels for As, Be, Hg, Sn, Tl and V. PERSPECTIVES: According to the current metal
      levels, RP-BWTP sludge might be used for agriculture purposes. However, for an
      environmentally safe use of sewage sludge, further studies including systematic
      monitoring are recommended. Annual metal concentrations and predicted variations
      of those elements in the sludge should be monitored.

PMID- 18062481
TI  - Using phytoremediation technologies to upgrade waste water treatment in Europe.
AB  - GOAL, SCOPE AND BACKGROUND: One of the burning problems of our industrial society
      is the high consumption of water and the high demand for clean drinking water.
      Numerous approaches have been taken to reduce water consumption, but in the long
      run it seems only possible to recycle waste water into high quality water. It
      seems timely to discuss alternative water remediation technologies that are fit
      for industrial as well as less developed countries to ensure a high quality of
      drinking water throughout Europe. MAIN FEATURES: The present paper discusses a
      range of phytoremediation technologies to be applied in a modular approach to
      integrate and improve the performance of existing wastewater treatment,
      especially towards the emerging micro pollutants, i.e. organic chemicals and
      pharmaceuticals. This topic is of global relevance for the EU. RESULTS: Existing
      technologies for waste water treatment do not sufficiently address increasing
      pollution situation, especially with the growing use of organic pollutants in the
      private household and health sector. Although some crude chemical approaches
      exist, such as advanced oxidation steps, most waste water treatment plants will
      not be able to adopt them. The same is true for membrane technologies.
      DISCUSSION: Incredible progress has been made during recent years, thus providing
      us with membranes of longevity and stability and, at the same time, high
      filtration capacity. However, these systems are expensive and delicate in
      operation, so that the majority of communities will not be able to afford them.
      Combinations of different phytoremediation technologies seem to be most promising
      to solve this burning problem. CONCLUSIONS: To quantify the occurrence and the
      distribution of micropollutants, to evaluate their effects, and to prevent them
      from passing through wastewater collection and treatment systems into rivers,
      lakes and ground water bodies represents an urgent task for applied environmental
      sciences in the coming years. RECOMMENDATIONS: Public acceptance of green
      technologies is generally higher than that of industrial processes. The EU should
      stimulate research to upgrade existing waste water treatment by implementing
      phytoremediation modules and demonstrating their reliability to the public.

PMID- 18062482
TI  - Phytoextraction of lead-contaminated soil using vetivergrass (Vetiveria
      zizanioides L.), cogongrass (Imperata cylindrica L.) and carabaograss (Paspalum
      conjugatum L.).
AB  - BACKGROUND, AIMS AND SCOPE: The global problem concerning contamination of the
      environment as a consequence of human activities is increasing. Most of the
      environmental contaminants are chemical by-products and heavy metals such as lead
      (Pb). Lead released into the environment makes its way into the air, soil and
      water. Lead contributes to a variety of health effects such as decline in mental,
      cognitive and physical health of the individual. An alternative way of reducing
      Pb concentration from the soil is through phytoremediation. Phytoremediation is
      an alternative method that uses plants to clean up a contaminated area. The
      objectives of this study were: (1) to determine the survival rate and vegetative
      characteristics of three grass species such as vetivergrass, cogongrass and
      carabaograss grown in soils with different Pb levels; and (2) to determine and
      compare the ability of the three grass species as potential phytoremediators in
      terms of Pb accumulation by plants. METHODS: The three test plants: vetivergrass
      (Vetiveria zizanioides L.); cogongrass (Imperata cylindrica L.); and carabaograss
      (Paspalum conjugatum L.) were grown in individual plastic bags containing soils
      with 75 mg kg(-1) (37.5 kg ha(-1)) and 150 mg kg(-1) (75 kg ha(-1)) of Pb,
      respectively. The Pb contents of the test plants and the soil were analyzed
      before and after experimental treatments using an atomic absorption
      spectrophotometer. This study was laid out following a 3 x 2 factorial experiment
      in a completely randomized design. RESULTS: On the vegetative characteristics of
      the test plants, vetivergrass registered the highest whole plant dry matter
      weight (33.85-39.39 Mg ha(-1)). Carabaograss had the lowest herbage mass
      production of 4.12 Mg ha(-1) and 5.72 Mg ha(-1) from soils added with 75 and 150
      mg Pb kg(-1), respectively. Vetivergrass also had the highest percent plant
      survival which meant it best tolerated the Pb contamination in soils.
      Vetivergrass registered the highest rate of Pb absorption (10.16 +/- 2.81 mg kg(
      1)). This was followed by cogongrass (2.34 +/- 0.52 mg kg(-1)) and carabaograss
      with a mean Pb level of 0.49 +/- 0.56 mg kg(-1). Levels of Pb among the three
      grasses (shoots + roots) did not vary significantly with the amount of Pb added
      (75 and 150 mg kg(-1)) to the soil. DISCUSSION: Vetivergrass yielded the highest
      biomass; it also has the greatest amount of Pb absorbed (roots + shoots). This
      can be attributed to the highly extensive root system of vetivergrass with the
      presence of an enormous amount of root hairs. Extensive root system denotes more
      contact to nutrients in soils, therefore more likelihood of nutrient absorption
      and Pb uptake. The efficiency of plants as phytoremediators could be correlated
      with the plants' total biomass. This implies that the higher the biomass, the
      greater the Pb uptake. Plants characteristically exhibit remarkable capacity to
      absorb what they need and exclude what they do not need. Some plants utilize
      exclusion mechanisms, where there is a reduced uptake by the roots or a
      restricted transport of the metals from root to shoots. Combination of high metal
      accumulation and high biomass production results in the most metal removal from
      the soil. CONCLUSIONS: The present study indicated that vetivergrass possessed
      many beneficial characteristics to uptake Pb from contaminated soil. It was the
      most tolerant and could grow in soil contaminated with high Pb concentration.
      Cogongrass and carabaograss are also potential phytoremediators since they can
      absorb small amount of Pb in soils, although cogongrass is more tolerant to Pb
      contaminated soil compared with carabaograss. The important implication of our
      findings is that vetivergrass can be used for phytoextraction on sites
      contaminated with high levels of heavy metals, particularly Pb. RECOMMENDATIONS
      AND PERSPECTIVES: High levels of Pb in localized areas are still a concern
      especially in urban areas with high levels of traffic, near Pb smelters, battery
      plants, or industrial facilities that burn fuel ending up in water and soils. The
      grasses used in the study, and particularly vetivergrass, can be used to
      phytoremediate urban soil with various contaminations by planting these grasses
      in lawns and public parks.

PMID- 18062483
TI  - Phytoremediation potentials of selected tropical plants for ethidium bromide.
AB  - BACKGROUND, AIMS AND SCOPE: Research and development has its own benefits and
      inconveniences. One of the inconveniences is the generation of enormous quantity
      of diverse toxic and hazardous wastes and its eventual contamination to soil and
      groundwater resources. Ethidium bromide (EtBr) is one of the commonly used
      substances in molecular biology experiments. It is highly mutagenic and
      moderately toxic substance used in DNA-staining during electrophoresis. Interest
      in phytoremediation as a method to solve chemical contamination has been growing
      rapidly in recent years. The technology has been utilized to clean up soil and
      groundwater from heavy metals and other toxic organic compounds in many countries
      like the United States, Russia, and most of European countries. Phytoremediation
      requires somewhat limited resources and very useful in treating wide variety of
      environmental contaminants. This study aimed to assess the potential of selected
      tropical plants as phytoremediators of EtBr. MATERIALS AND METHODS: This study
      used tomato (Solanum lycopersicum), mustard (Brassica alba), vetivergrass
      (Vetiveria zizanioedes), cogongrass (Imperata cylindrica), carabaograss (Paspalum
      conjugatum), and talahib (Saccharum spontaneum) to remove EtBr from laboratory
      wastes. The six tropical plants were planted in individual plastic bags
      containing soil and 10% EtBr-stained agarose gel. The plants were allowed to
      establish and grow in soil for 30 days. Ethidium bromide content of the test
      plants and the soil were analyzed before and after soil treatment. Ethidium
      bromide contents of the plants and soils were analyzed using an UV VIS
      spectrophotometer. RESULTS: Results showed a highly significant (p< or =0.001)
      difference in the ability of the tropical plants to absorb EtBr from soils.
      Mustard registered the highest absorption of EtBr (1.4+/-0.12 microg kg(-1))
      followed by tomato and vetivergrass with average uptake of 1.0+/-0.23 and 0.7+/
      0.17 microg kg(-1) EtBr, respectively. Cogongrass, talahib, and carabaograss had
      the least amount of EtBr absorbed (0.2+/-0.6 microg kg(-1)). Ethidium bromide
      content of soil planted to mustard was reduced by 10.7%. This was followed by
      tomato with an average reduction of 8.1%. Only 5.6% reduction was obtained from
      soils planted to vetivergrass. Soils planted to cogongrass, talahib, and
      carabaograss had the least reduction of 1.52% from its initial EtBr content.
      DISCUSSION: In this study, mustard, tomato, and vetivergrass have shown their
      ability to absorb EtBr from contaminated soil keeping them from expanding their
      reach into the environment and preventing further contamination. Its downside,
      however, is that living creatures including humans, fish, and birds, must be
      prevented from eating the plants that utilized these substances. Nonetheless, it
      is still easier to isolate, cut down, and remove plants growing on the surface of
      the contaminated matrices, than to use strong acids and permanganates to
      chemically neutralize a dangerous process that can further contaminate the
      environment and pose additional risks to humans. Though this alternative method
      does not totally eliminate eventual environmental contamination, it is by far
      produces extremely insignificant amount of by-products compared with the existing
      processes and technologies. CONCLUSIONS: Mustard had the highest potential as
      phytoremediator of EtBr in soil. However, the absorption capabilities of the
      other test plants may also be considered in terms of period of maturity and
      productivity. RECOMMENDATIONS AND PERSPECTIVES: It is recommended that a more
      detailed and complete investigation of the phytoremediation properties of the
      different plants tested should be conducted in actual field experiments. Plants
      should be exposed until they reach maturity to establish their maximum response
      to the toxicity and mutagenecity of EtBr and their maximum absorbing
      capabilities. Different plant parts should be analyzed individually to determine
      the movement and translocation of EtBr from soil to the tissues of plants. Since
      this study has established that some plants can thrive and dwell in EtBr-treated
      soil, an increased amount of EtBr application should be explored in future
      studies. It is suggested therefore that a larger, more comprehensive exploration
      of phytoremediation application in the management of toxic and hazardous wastes
      emanating from biotechnology research activities should be considered especially
      on the use of vetivergrass, a very promising tropical perennial grass.

PMID- 18062484
TI  - Metabolic responses of weeping willows to selenate and selenite.
AB  - GOAL, SCOPE AND BACKGROUND: Selenium (Se) is one of the most widely distributed
      elements of the earth's crust at low concentrations. The extensive use of Se
      containing chemicals due to anthropogenic activities has increased the ecological
      risk to environmental compartments. Plants, under unfavorable environmental
      conditions, often increase the formation of reactive oxygen species (ROS), and
      consequently plant antioxidant enzymatic systems have been proposed to be
      important in plant stress tolerance. The goal of this study was to find out the
      metabolic responses of plants to Se, to provide quantitative information whether
      exogenous Se has a beneficial role in plants, and to investigate the potential of
      vegetation management of Se for potential phytoremediation. MATERIAL AND METHODS:
      Pre-rooted plants of weeping willows (Salix babylonica L.) were grown
      hydroponically in growth chambers and treated with Na2SeO4 or Na2SeO3 at 24.0 +/-
      1 degrees C for 168 h. Five different treatment concentrations were used, ranging
      from 0.44 to 8.72 mg Se/L for the treatments exposed to SeO4(2-) and from 0.50 to
      10.0 mg Se/L for the treatments exposed to SeO3(2-), respectively. Transpiration
      rates, soluble protein contents and antioxidative enzyme activities of the plants
      were monitored to evaluate toxicity from exogenous Se exposure. At the end of the
      study, total Se in the hydroponic solution was analyzed by hydride generation
      atomic fluorescence spectrometry (HG-AFS). RESULTS: Both chemical forms of Se at
      low concentrations showed growth-promoting effects on plants. A significant
      decrease of transpiration rates and of soluble protein contents of plants was
      observed at higher Se concentrations after 168 h of exposure. Measurable change
      of superoxide dismutases (SOD) activity in leaves was only detected under high Se
      treatments. Catalase (CAT) activity was significantly affected by the Se
      application. Slight change of peroxidase (POD) activity was measured in all
      treatments, whereas significant inhibition of POD activity was detected for the
      plants exposed to SeO3(2-) of 10.0 mg Se/L. Se-induced stress appeared in all
      treatments, thus resulting in measurable increase of glutathione peroxidase (GSH
      Px) activity of the plants. Although both chemical forms of Se were taken up by
      weeping willows efficiently, their uptake rates were different. DISCUSSION: Of
      all measured parameters, POD and CAT activities in leaves were noted the most
      sensitive indicator for the plants exposed to SeO4(2-) and SeO3(2-),
      respectively. Deleterious effects on plant physiological functions due to Se
      application were not observed over 168 h of exposure. This is largely due to the
      fact that well-established antioxidant enzymatic systems in plants and higher
      activities of GSH-Px largely reduced the negative effects on plants; SeO3(2-)
      caused much more severe stress to plants than SeO4(2-) at higher Se application
      rates. The uptake mechanisms between the two chemical species were quite
      different. CONCLUSIONS: Neither visible toxic symptoms nor metabolic lesions were
      observed at low concentrations of Se, probably due to the effective established
      enzymatic systems in weeping willows. All selected parameters for toxicity
      determination were significantly correlated to Se application, but metabolic
      responses of plants to SeO4(2-) and SeO3(2-) were quite different. GSH-Px in
      leaves was probably the principle enzyme responsible for stress reduction from Se
      exposure. Due to their different chemical properties, weeping willows showed a
      faster uptake rate for SeO4(2-) than for SeO3(2-). RECOMMENDATIONS: Exogenous Se
      has a beneficial role in plants and vegetation management of Se is a potential
      remediation strategy in cleaning up Se-contaminated sites. Further investigation
      on the biochemical mechanism of Se metabolism will provide insight to the
      specific interactions between Se and plants on the molecular level. PERSPECTIVES:
      Weeping willow has a sound potential for phytoremediation of Se-contaminated
      sediment and groundwater because the tree is not only tolerant to Se but also
      uptakes chemical species from the environment.

PMID- 18062485
TI  - Selective removal of heavy metals from metal-bearing wastewater in a cascade line
      reactor.
AB  - GOAL, SCOPE AND BACKGROUND: This paper is a part of the research work on
      'Integrated treatment of industrial wastes towards prevention of regional water
      resources contamination - INTREAT' the project. It addresses the environmental
      pollution problems associated with solid and liquid waste/effluents produced by
      sulfide ore mining and metallurgical activities in the Copper Mining and Smelting
      Complex Bor (RTB-BOR), Serbia. However, since the minimum solubility for the
      different metals usually found in the polluted water occurs at different pH
      values and the hydroxide precipitates are amphoteric in nature, selective removal
      of mixed metals could be achieved as the multiple stage precipitation. For this
      reason, acid mine water had to be treated in multiple stages in a continuous
      precipitation system-cascade line reactor. MATERIALS AND METHODS: All experiments
      were performed using synthetic metal-bearing effluent with chemical a composition
      similar to the effluent from open pit, Copper Mining and Smelting Complex Bor
      (RTB-BOR). That effluent is characterized by low pH (1.78) due to the content of
      sulfuric acid and heavy metals, such as Cu, Fe, Ni, Mn, Zn with concentrations of
      76.680, 26.130, 0.113, 11.490, 1.020 mg/dm3, respectively. The cascade line
      reactor is equipped with the following components: for feeding of effluents, for
      injection of the precipitation agent, for pH measurements and control, and for
      removal of the process gases. The precipitation agent was 1M NaOH. In each of the
      three reactors, a changing of pH and temperature was observed. In order to
      verify. efficiency of heavy metals removal, chemical analyses of samples taken at
      different pH was done using AES-ICP. RESULTS: Consumption of NaOH in reactors was
      370 cm3, 40 cm3 and 80 cm3, respectively. Total time of the experiment was 4 h
      including feeding of the first reactor. The time necessary to achieve the defined
      pH value was 25 min for the first reactor and 13 min for both second and third
      reactors. Taking into account the complete process in the cascade line reactor,
      the difference between maximum and minimum temperature was as low as 6 degrees C.
      The quantity of solid residue in reactors respectively was 0.62 g, 2.05 g and
      3.91 g. In the case of copper, minimum achieved concentration was 0.62 mg/dm3 at
      pH = 10.4. At pH = 4.50 content of iron has rapidly decreased to < 0.1 mg/dm3 and
      maintained constant at all higher pH values. That means that precipitation has
      already ended at pH=4.5 and maximum efficiency of iron removal was 99.53%. The
      concentration of manganese was minimum at pH value of 11.0. Minimum obtained
      concentration of Zn was 2.18 mg/dm3 at a pH value of 11. If pH value is higher
      than 11, Zn can be re-dissolved. The maximum efficiency of Ni removal reached
      76.30% at a pH value of 10.4. DISCUSSION: Obtained results show that efficiency
      of copper, iron and manganese removal is very satisfactory (higher than 90%). The
      obtained efficiency of Zn and Ni removal is lower (72.30% and 76.31%,
      respectively). The treated effluent met discharge water standard according to The
      Council Directive 76/464/EEC on pollution caused by certain dangerous substances
      into the aquatic environment of the Community. Maximum changing of temperature
      during the whole process was 6 degrees C. CONCLUSION: This technology, which was
      based on inducing chemical precipitation of heavy metals is viable for selective
      removal of heavy metals from metal-bearing effluents in three reactor systems in
      a cascade line. RECOMMENDATIONS AND PERSPECTIVES: The worldwide increasing
      concern for the environment and guidelines regarding effluent discharge make
      their treatment necessary for safe discharge in water receivers. In the case
      where the effluents contain valuable metals, there is also an additional economic
      interest to recover these metals and to recycle them as secondary raw materials
      in different production routes.

PMID- 18062486
TI  - Testing antimicrobial cleaner efficacy on gypsum wallboard contaminated with
      Stachybotrys chartarum.
AB  - GOAL, SCOPE AND BACKGROUND: Reducing occupant exposure to indoor mold is the goal
      of this research, through the efficacy testing of antimicrobial cleaners. Often
      mold contaminated building materials are not properly removed, but instead
      surface cleaners are applied in an attempt to alleviate the problem. The efficacy
      of antimicrobial cleaners to remove, eliminate or control mold growth on surfaces
      can easily be tested on non-porous surfaces. However, the testing of
      antimicrobial cleaner efficacy on porous surfaces, such as those found in the
      indoor environment such as gypsum board can be more complicated and prone to
      incorrect conclusions regarding residual organisms. The mold Stachybotrys
      chartarum has been found to be associated with idiopathic pulmonary hemorrhage in
      infants and has been studied for toxin production and its occurrence in water
      damaged buildings. Growth of S. chartarum on building materials such as gypsum
      wallboard has been frequently documented. METHODS: Research to control S.
      chartarum growth using 13 separate antimicrobial cleaners on contaminated gypsum
      wallboard has been performed in laboratory testing. Popular brands of cleaning
      products were tested by following directions printed on the product packaging.
      RESULTS: A variety of gypsum wallboard surfaces were used to test these cleaning
      products at high relative humidity. The results indicate differences in
      antimicrobial efficacy for the six month period of testing. DISCUSSION: Results
      for the six types of GWB surfaces varied extensively. However, three cleaning
      products exhibited significantly better results than others. Lysol All-Purpose
      Cleaner-Orange Breeze (full strength) demonstrated results which ranked among the
      best in five of the six surfaces tested. Both Borax and Orange Glo Multipurpose
      Degreaser demonstrated results which ranked among the best in four of the six
      surfaces tested. CONCLUSIONS: The best antimicrobial cleaner to choose is often
      dependent on the type of surface to be cleaned of S. chartarum contamination. For
      Plain GWB, no paint, the best cleaners were Borax, Lysol All-Purpose Cleaner
      Orange Breeze (full strength), Orange Glo Multipurpose Degreaser, and Fantastik
      Orange Action. RECOMMENDATIONS AND PERSPECTIVES: These results are not meant to
      endorse the incomplete removal of mold contaminated building materials. However,
      it is recognized that complete removal may not always be possible and solutions
      to control mold regrowth may contribute to reduced occupant exposure. Current
      recommendations of removal and replacement of porous building materials should be
      followed. It is not the intension of this discussion to endorse any product.
      Reporting on the performance of these products under the stated conditions was
      and remains the only purpose.

PMID- 18062487
TI  - Fractionation and mobility of phosphorus in a sandy forest soil amended with
      biosolids.
AB  - GOAL, SCOPE AND BACKGROUND: Biosolids, i.e., treated sewage sludge, are commonly
      used as a fertilizer and amendment to improve soil productivity. Application of
      biosolids to meet the nitrogen (N) requirements of crops can lead to accumulation
      of phosphorus (P) in soils, which may result in P loss to water bodies. Since
      1996, biosolids have been applied to a Pinus radiata D. Don plantation near
      Nelson City, New Zealand, in an N-deficient sandy soil. To investigate
      sustainability of the biosolids application programme, a long-term research trial
      was established in 1997, and biosolids were applied every three years, at three
      application rates, including control (no biosolids), standard and high
      treatments, based on total N loading. The objective of this study was to evaluate
      the effect of repeated application of biosolids on P mobility in the sandy soil.
      MATERIALS AND METHODS: Soil samples were collected in August 2004 from the trial
      site at depths of 0-10, 10-25, 25-50, 50-75, and 75-100 cm. The soil samples were
      analysed for total P (TP), plant-available P (Olsen P and Mehlich 3 P), and
      various P fractions (water-soluble, bioavailable, Fe and Al-bound, Ca-bound, and
      residual) using a sequential P fractionation procedure. RESULTS AND DISCUSSION:
      Soil TP and Olsen P in the high biosolids treatment (equivalent to 600 kg N ha(
      1) applied every three years) had increased significantly (P<0.05) in both 0-10
      cm and 10-25 cm layers. Mehlich 3 P in soil of the high treatment had increased
      significantly only at 0-10 cm. Olsen P appeared to be more sensitive than Mehlich
      3 P as an indicator of P movement in a soil profile. Phosphorus fractionation
      revealed that inorganic P (Al/Fe-bound P and Ca-bound P) and residual P were the
      main P pools in soil, whereas water-soluble P accounted for approximately 70% of
      TP in biosolids. Little organic P was found in either the soil or biosolids.
      Concentrations of water-soluble P, bioavailable inorganic P (NaHCO3 Pi) and
      potentially bioavailable inorganic P (NaOH Pi) in both 0-10 and 10-25 cm depths
      were significantly higher in the high biosolids treatment than in the control.
      Mass balance calculation indicated that most P applied with biosolids was
      retained by the top soil (0-25 cm). The standard biosolids treatment (equivalent
      to 300 kg N ha(-1) applied every three years) had no significant effect on
      concentrations of TP, Mehlich 3 P and Olsen P, and P fractions in soil.
      CONCLUSIONS: The results indicate that the soil had the capacity to retain most
      biosolids-derived P, and there was a minimal risk of P losses via leaching in the
      medium term in the sandy forest soil because of the repeated biosolids
      application, particularly at the standard rate. RECOMMENDATIONS AND PERSPECTIVES:
      Application to low-fertility forest land can be used as an environmentally
      friendly option for biosolids management. When biosolids are applied at a rate to
      meet the N requirement of the tree crop, it can take a very long time before the
      forest soil is saturated with P. However, when a biosolids product contains high
      concentrations of P and is applied at a high rate, the forest ecosystem may not
      have the capacity to retain all P applied with biosolids in the long term.

PMID- 18062488
TI  - Traumatic swelling of the medial rectus muscle clinically mimicking muscle
      disinsertion or transection.

PMID- 18062489
TI  - Immediate postoperative strabismus management.

PMID- 18062490
TI  - What's your diagnosis? Axenfeld-Rieger anomaly without glaucoma.

PMID- 18062491
TI  - The effects of early surgery for infantile esotropia on psychomotor development.

PMID- 18062492
TI  - Optical coherence tomography applications in pediatric ophthalmology.
AB  - In pediatric ophthalmology, test results may be limited by a child's ability to
      cooperate. Invasive and contact methods such as applanation tonometry, ultrasound
      biometry, and pachymetry are sometimes difficult to perform. Optical coherence
      tomography (OCT) has become a widely used noncontact method to obtain cross
      sections of various ocular structures. In this review, we describe the principles
      and clinical applications of OCT, with special attention to pediatric
      ophthalmology.

PMID- 18062493
TI  - Assessment of psychomotor development before and after strabismus surgery for
      infantile esotropia.
AB  - PURPOSE: To assess motor and mental development before and after strabismus
      surgery in children with infantile esotropia. PATIENTS AND METHODS: Mental and
      motor development indexes of 20 children with infantile esotropia without
      neurologic abnormalities and 17 age-matched healthy control subjects were
      prospectively tested at regular intervals before and after strabismus surgery
      with the Dutch version of the Bayley and ordinal scales of infant development.
      RESULTS: The mean age for surgery in the study group was 13.5 months. Before
      strabismus surgery, the Bayley scales of infant development showed a significant
      delay in both mental (P < .045) and motor (P < .008) development for children
      with infantile esotropia compared with the control group. Three weeks after
      surgery, the delay in mental development had disappeared. The delay in motor
      development persisted for months. Two of the 7 ordinal scales--object permanence
      (P < .01) and means-end (P < .036)--showed a statistically significant delay for
      children with infantile esotropia. Three weeks after strabismus surgery, there
      was no difference between the study group and the control group. CONCLUSIONS:
      Children with infantile esotropia had delayed motor and mental development
      compared with healthy children. After strabismus surgery, patients recovered
      mentally, but their motor delays persisted for months when tested with the Bayley
      scales of infant development.

PMID- 18062495
TI  - Deficient motion-defined and texture-defined figure-ground segregation in
      amblyopic children.
AB  - PURPOSE: Motion-defined form deficits in the fellow eye and the amblyopic eye of
      children with amblyopia implicate possible direction-selective motion processing
      or static figure-ground segregation deficits. Deficient motion-defined form
      perception in the fellow eye of amblyopic children may not be fully accounted for
      by a general motion processing deficit. This study investigates the contribution
      of figure-ground segregation deficits to the motion-defined form perception
      deficits in amblyopia. METHODS: Performances of 6 amblyopic children (5
      anisometropic, 1 anisostrabismic) and 32 control children with normal vision were
      assessed on motion-defined form, texture-defined form, and global motion tasks.
      RESULTS: Performance on motion-defined and texture-defined form tasks was
      significantly worse in amblyopic children than in control children. Performance
      on global motion tasks was not significantly different between the 2 groups.
      CONCLUSION: Faulty figure-ground segregation mechanisms are likely responsible
      for the observed motion-defined form perception deficits in amblyopia.

PMID- 18062494
TI  - Corrective lens wear among adolescents: findings from the National Health and
      Nutrition Examination Survey.
AB  - PURPOSE: To evaluate demographic variations in the use of corrective lenses among
      adolescents. METHODS: Cross-sectional analysis of 3,916 adolescents between ages
      12 and 18 years who participated in the 1999-2002 National Health and Nutrition
      Examination Survey (NHANES) vision examination component, which included
      questions regarding use of corrective lenses, distance visual acuity (VA; with
      corrective lenses if available), and non-cycloplegic autorefraction. Results
      reflect population-level estimates. RESULTS: Overall, 32.2% (95% confidence
      interval [CI], 29.5%-35.0%) reported wearing corrective lenses. The adjusted odds
      of reporting corrective lens wear were greater for female and privately insured
      participants. In contrast, the adjusted odds of having corrective lenses
      available at the time of NHANES participation were greater for participants
      between ages 15 and 18 years compared with those between 12 and 14 years, and
      participants who were white compared with those who were black or Hispanic.
      Although 12.6% (95% CI, 8.8%-16.3%) of participants without their corrective
      lenses available for the NHANES had 20/25 or better distance VA in both eyes,
      26.9% (95% CI, 21.6%-32.1%) of those with their corrective lenses had distance VA
      of 20/40 or worse in at least 1 eye. Near VA was not measured and participants
      with their corrective lenses available had only their corrected distance VA
      measured. No data regarding the accuracy of the NHANES assessment of distance VA
      are available. Autorefraction was performed without cycloplegia. CONCLUSIONS:
      Many adolescents report wearing corrective lenses. Variations across demographic
      characteristics are possibly due to a combination of undertreatment,
      overtreatment, and compliance with previously recommended corrective lenses.

PMID- 18062496
TI  - Bilateral papillitis associated with bilateral anterior uveitis in a child.
AB  - Slit-lamp and dilated fundus examination of a 6-year-old boy revealed bilateral
      anterior uveitis associated with optic disk edema with mild leakage on
      fluorescein angiography in both eyes. Anterior uveitis resolved with topical
      therapy in 3 months and optic disk edema and fluorescein leakage 1 month later.
      Optic nerve function was intact. Resolution of optic disk edema followed that of
      anterior uveitis with no sequelae.

PMID- 18062497
TI  - Posterior scleritis in a 7-month-old infant.
AB  - This article describes a 7-month-old infant with posterior scleritis, diagnosed
      on the basis of B-scan ultrasonography and computed tomography. The patient was
      initially diagnosed with preseptal cellulitis and endophthalmitis. Posterior
      scleritis should be considered in the differential diagnosis of acute orbital
      inflammation in children younger than 1 year.

PMID- 18062498
TI  - Fibrous histiocytoma of the eyelid obliterating the punctum and the canaliculus.
AB  - A 17-year-old boy with a growth in the medial right lower eyelid obliterating the
      lower punctum and canaliculus underwent incisional biopsy, which revealed fibrous
      histiocytoma. The remaining tumor was excised and the eyelid was reconstructed.
      No recurrence was noted after 1 year of follow-up.

PMID- 18062499
TI  - Congenital joining of the eyelids in a neonate.

PMID- 18062500
TI  - [And if it was necessary to convince...].

PMID- 18062501
TI  - [From histology via genetic signature to an improved treatment of breast cancer
      patients].
AB  - Today, breast cancer prognosis and (neo-) adjuvant treatment selection are based
      on clinical as well as on histological and immunohistochemical data. Will genetic
      expression profiles have a better predictive value? Ongoing studies will provide
      the answer.

PMID- 18062502
TI  - [Breast cancer surgery].
AB  - Breast conserving surgery followed by radiation therapy is the treatment of
      choice for early breast cancer. For patients who choice or need a mastectomy,
      breast reconstruction provides an acceptable alternative. Breast cancer surgery
      has been evolving through minimally invasive approaches. Sentinel node biopsy has
      already remplaced axillary lymph node dissection in the evaluation of the axilla.
      Local ablation of the tumor may be a valuable alternative to surgery in the
      future.

PMID- 18062503
TI  - [Indications of radiation therapy in non metastatic breast cancer].
AB  - In this review, we will consider 4 principal topics concerning the role of
      radiotherapy (RT) in the treatment of breast cancer. In early invasive carcinoma,
      RT on the breast volume followed by a boost to the tumoral bed is recommended
      after conservative surgery, especially in young patients. After mastectomy, RT is
      considered as a standard for locally advanced carcinoma because it decreases the
      rate of local relapse. The majority of ductal carcinoma in situ can be treated by
      tumorectomy but the margins must be negative. In this situation, however,
      radiotherapy is always indicated and offers a satisfactory local control.
      Concerning the sequence, the priority is given to the systemic treatments, but RT
      should also be able to start as soon as possible.

PMID- 18062504
TI  - [Aromatase inhibitors in the adjuvant treatment of postmenopausal patients with
      early breast cancer: a little, a lot or no way?].
AB  - Several large randomized trials showed that tamoxifen alone is no more the
      standard adjuvant hormonal therapy for menopausal patients. Aromatase inhibitors,
      given upfront or sequentially after tamoxifen, confirmed their efficacy by
      improving disease free survival, risk of distant metastasis and overall survival
      in some situations or subgroups of patients. These drugs are usually well
      tolerated, but they clearly increase bone mineral density loss as well as the
      risk of fractures and their long term safety on the cardio-vascular system needs
      to be followed. Thus, even if the role of the aromatase inhibitors is now evident
      in the adjuvant therapy of postmenopausal women the benefice/risk ratio should be
      carefully evaluated for each patient.

PMID- 18062505
TI  - [Role of surgery for metastatic breast cancer at diagnosis].
AB  - Metastatic breast cancer is considered as incurable. Treatments of choice are
      systemic and palliative. Surgery of the primary tumor is usually indicated for
      palliation of local complications. However recently published studies seem to
      demonstrate that the surgical excision of the primary tumor increase survival, in
      particular for patients with negative surgical margins or with only bone
      metastases. As these studies have been adjusted for factors that may induce
      biais, only a prospective clinical randomized trial may confirm the role of
      surgery in the management of metastatic breast cancer.

PMID- 18062506
TI  - [Collaboration patients-health care providers].
AB  - Breast cancer is the most common cancer in women. Daily suffering of patients and
      their relatives is often ignored or underestimated. Scientific advances focus on
      medical treatments and survival and very little on the psychosocial impact of the
      disease. The shared expertise between breast cancer patients and health care
      providers is an innovative and promising approach aiming to provide better
      quality of life and care. The participation of patients permits to bring together
      professionals around common goals and to promote multidisciplinary disease
      management, networking and global care. Focusing on very concrete problems
      highlighted from patients' expertise also improves research, medical training,
      and health policy standards.

PMID- 18062507
TI  - [Malignant non-Hodgkin's lymphomas in children. A maximum survival with a minimum
      sequellae].

PMID- 18062508
TI  - [Medical-legal aspects of an expert paternity research].

PMID- 18062509
TI  - [Intelligence and general medicine...].

PMID- 18062510
TI  - [Twenty-two centuries to understand that blood circulates].

PMID- 18062511
TI  - [Paris, September 2007; a bioethics day (2)].

PMID- 18062513
TI  - [To communicate in the dark].

PMID- 18062512
TI  - [French customs: your DNA, please (3)].

PMID- 18062514
TI  - Mentorship program in mental health: time to develop a new academic relationship.

PMID- 18062515
TI  - Prenatal diagnosis of beta-thalassaemia by chorionic villous sampling.
AB  - OBJECTIVE: To establish intrauterine diagnosis of thalassaemia major in couples
      with thalassaemia trait by chorionic villous sampling. METHODS: A total of 60
      couples with children suffering from transfusion dependent beta-thalassaemia or
      couples who were known carriers of beta-thalassaemia were included in this study.
      The standard procedure was followed for the collection of samples which was
      finally transferred in appropriate medium to Armed Forces Institute of Pathology
      Rawalpindi for detection of thalassaemia mutation. RESULTS: After DNA analysis of
      the submitted samples, no thalassaemia mutation was detected in the foetus in 24
      cases. In 8 cases foetus were heterozygote for thalassaemia having a single
      mutation. In 28 cases, foetus were homozygous for beta-thalassaemia. CONCLUSION:
      Appropriate and extensive screening, accurate detection and counseling of at risk
      couples, along with antenatal diagnosis is a promising strategy for the reduction
      of mortality and morbidity from thalassaemia in countries where it is prevalent.
      Based on these results, it can be concluded that prenatal diagnosis of beta
      thalassaemia for prevention can be done using chorionic villous sampling.

PMID- 18062516
TI  - A decade of cardiothoracic surgery at a tertiary care hospital in Karachi,
      Pakistan.
AB  - OBJECTIVE: The medical records at Aga Khan University were reviewed to analyze
      the trends, mortality and patients characteristics of cardiothoracic surgeries in
      the last decade. METHOD: The medical records of all adult cardiac, thoracic and
      combined cardiothoracic operations performed during January 1995 to December 2004
      at the Aga Khan University Hospital were reviewed. Data were retrieved and
      analyzed for trends, patient characteristics, and procedure mortality. RESULTS:
      From January 1995 - December 2004, 4553 cases were eligible for the study, of
      which 73% were males and 9.4% were children. Male to female ratio changed from
      1.3:1 to 3:1 from childhood to adulthood. Number of patients requiring
      cardiothoracic intervention increased continuously throughout the period, cardiac
      operations outnumbering thoracic or combined procedures. Ten-year average annual
      mortality remained 4.8% with slight variation per annum. Age distribution of
      cardiac surgery patients remained the same, however, constantly increasing number
      of over-70-year olds was observed. Mortality for isolated CABG, isolated valve
      and CABG with valve remained 1.9%, 4.3% and 18.3% respectively. CONCLUSION:
      Trends of cardiothoracic procedures appear similar to those in the developed
      countries, so are the mortality figures.

PMID- 18062517
TI  - Patient's outcome of bladder cancer managed by radical cystectomy with
      lymphadenectomy at a university hospital.
AB  - OBJECTIVE: To study the impact of tumour staging and nodal metastases in
      predicting 5- year's survival after radical cystectomy and bilateral pelvic
      lymphadenectomy for primary bladder cancer. METHODS: During the period 1995 to
      2005, 58 patients underwent radical cystectomy and bilateral pelvic
      lymphadenectomy and urinary diversion at a University hospital. Patients were
      identified using medical indexing coding system (ICD 9CM) using standard key
      words. The patient records were analyzed and follow up data updated. Disease
      specific survival, death or recurrence was taken as end point. RESULTS: Out of 58
      patients, 50 (86%) were males and 8 (14%) females with a mean age of 61 +/- 13.1
      years (range from 27 to 87 years). Of 58 patients, 11 (23%) were excluded from
      the study because of in adequate follow up. The mean follow up was 5.7 years
      (range, 7 months to 11 years). The overall 5 years survival was 55% with disease
      specific survival being 66%. Patients with pathological stage TO at cystectomy
      have 87% 5 years disease specific survival compared to 60%, in patients with pT4
      (p = 0.705). The 5-year survival for node positive patients was 16%, compared to
      60% for node negative patients (p < 0.01). CONCLUSIONS: Radical cystectomy and
      bilateral pelvic lymphadenectomy is the standard treatment for muscle invasive
      and high grade T1 cancers, and as salvage for recurrent cancers. Lymphadenectomy
      has a potential therapeutic benefit. The pathological stage at cystectomy and
      nodal status are predictors of 5 years survival.

PMID- 18062518
TI  - Medico-legal assessment of sexual assault victims in Lahore.
AB  - OBJECTIVE: The objective of the study was the medico-legal assessment of sexual
      assault victims in Lahore, and to know the characteristics of the assailants in
      these cases. METHODS: This study included all 123 female cases of alleged sexual
      assault that presented for medical examination at the office of the surgeon
      medico-legal Punjab at Lahore during 2002. RESULTS: Around 64% of the victims
      were between 10-19 years of age, 76% presented for medical examination after a
      delay of more than 72 hours. The assailant was known to the victim in 57% cases.
      Two or more assailants were involved in 30% cases. The victims had changed
      clothes and washed their bodies before the medical examination in 83% cases.
      Physical evidence of violence on the body was present in only 15% of the victims
      and evidence of recent injury to the genital tract was present in 18%
      individuals. However a positive semen analysis was reported in 98.35% of the
      samples. CONCLUSIONS: Sexual assault was more common in younger females. Late
      presentation for examination was due to the embarrassment of being exposed. A
      positive semen analysis was the definite factor for confirmation of the assault.

PMID- 18062519
TI  - Attenuation of hypotension using phenylephrine during induction of anaesthesia
      with propofol.
AB  - OBJECTIVE: To observe if phenylephrine mixed with propofol can attenuate
      hypotensive effects of propofol during induction of anaesthesia. METHODS: A total
      number of 135 adult ASA-I and ASA-II patients were divided into three groups.
      (Group A, B and C). All patients were induced with propofol 2.5 mg per kg. In
      Group A (control group) patients received propofol mixed with 2cc of 0.9% normal
      saline. Group B (study group) patients received propofol mixed with 2cc of a
      solution containing phenylephrine 25 microg/cc (total 50 microg); Group C (study
      group) patients received propofol mixed with 2cc of a solution containing
      phenylephrine 50 microg/cc (total 100 microg). Haemodynamic variables like
      systolic, diastolic, mean arterial blood pressure and heart rate were noted.
      Hypotension was defined as 20% decrease in baseline systolic blood pressure
      recorded before induction of anaesthesia. RESULTS: Phenylephrine in a dose of 100
      micrograms attenuated the drop in systolic blood pressure. However phenylephrine
      in a dose 50 micrograms did not effectively prevent anticipated drop in SBP.
      CONCLUSION: Phenylephrine in doses of 100 micrograms effectively attenuates
      anticipated hypotension upon induction of general anaesthesia with propofol.

PMID- 18062520
TI  - Comparison of two sedation techniques in patients undergoing surgical procedures
      under regional anaesthesia.
AB  - OBJECTIVE: Intraoperative comfort and patient satisfaction during surgical
      procedures under regional anaesthesia can be improved with the use of
      supplemental intravenous sedation. The authors conducted a study to compare two
      sedation techniques for surgical procedures performed under regional anaesthesia,
      i.e., midazolam and pethidine combination compared with midazolam and tramadol
      combination. METHODS: Forty adult American Society of Anaesthesiologists (ASA)
      grade 1-111 patients, aged between 40-65 years undergoing surgery under regional
      anaesthesia (sub-arachnoid block) were included. The patients were randomly
      divided into two groups. All patients received standardized premedication,
      intraoperative monitoring and oxygen therapy. Group A patients received midazolam
      0.03 mg/kg followed by pethidine 20 mg intravenously, and group B patients
      received midazolam 0.03 mg/kg followed by tramadol 20 mg intravenously after the
      institution of regional anaesthesia. Monitoring included ECG, blood pressure,
      respiratory rate, oxygen saturation and sedation score. Complications, if any,
      were recorded. Monitoring was continued during the recovery room stay. All
      patients were interviewed in the evening and time of ambulation and rating of OR
      experience was noted. RESULTS: Data analysis showed no significant difference
      between pethidine and tramadol for all the haemodynamic variables (p = > 0.05).
      There was also no significant difference in patient's and surgeon's assessment of
      their experience. Complications and recovery characteristics also did not show
      any significant difference. CONCLUSION: Midazolam-tramadol combination may be
      used as an alternative to midazolam-pethidine combination for sedation during
      surgical procedures performed under regional anaesthesia.

PMID- 18062521
TI  - Hystroscopic management of Ashermans syndrome.
AB  - OBJECTIVE: To confirm the diagnosis of Asherman's syndrome in patients with
      scanty menses/amenorrhoea or infertility and to assess the effectiveness of
      hysteroscopy in the treatment of Asherman's syndrome. METHODS: A hospital based
      descriptive study conducted on 20 patients presenting with amenorrhoea,
      oligomenorrhoea, or infertility from Jan 2004 to June 2005. They were selected
      after excluding hormonal imbalances, premature ovarian failure and congenital
      uterine abnormalities. All patients underwent diagnostic hysteroscopy and
      resection of adhesions. Specimens were sent for Histopathology and bacterial
      culture. RESULT: A total of 20 patients were included in this study, the median
      age was 26 years, 65% had presented with scanty menses with secondary
      infertility, 20% with secondary ammenorrhoea, and 15% with primary infertility
      alone. Hysteroscopic findings showed thick fibrous adhesions in 45% patients, 40%
      had flimsy adhesions and 15% had muscular adhesions. It was seen that 65% had
      adhesions in the body of uterus, 25% at the site of internal os and 1% had
      adhesions in the cervical canal as well as the body of the uterus. Normal
      menstrual cycle was resumed in 95% patients, whereas two patients conceived and
      were followed to term. Dense fibrous tissue with few patches of calcification and
      no signs of secretory or proliferative cells was found in 35% patients. In 45%
      endometrium showed proliferative changes and collagen fibers. Only 1 patient had
      a positive AFB culture and the histopathology showed few graulomas with
      epitheloid cells most of the tissue replaced by necrotic tissue with patchy areas
      of caseation. CONCLUSION: Hysteroscopy is an effective procedure for not only
      diagnosing Ashermans Syndrome, but is equally effective for treating it..

PMID- 18062522
TI  - Paving the way for evidence-based medicine in Pakistan.
AB  - Evidence-based Medicine (EBM) is the process of systematically reviewing,
      appraising and using clinical research findings to aid the delivery of optimal
      clinical care to patients. EBM has become popular due to: the need for valid
      information about diagnosis, prognosis, therapy and prevention during patient
      care; traditional sources such as textbooks and expert opinion being frequently
      out-of-date; and knowledge of current best evidence declining with time from
      graduation from medical college. EBM has become feasible for practicing
      clinicians due to: new strategies for appraising studies; availability of
      systematic reviews (summaries) of current best evidence; and information
      technology (computers with Internet access). In a resource-limited country such
      as Pakistan, an evidence-based approach can be cost-effective by reducing
      clinical practices that have no proven benefit. Commonly perceived obstacles to
      EBM include limited access to computers, the Internet and online resources.
      Reliable resources of EBM are available (such as The Cochrane Database of
      Systematic Reviews http://www.cochrane.org) although many of these require paid
      subscriptions. Another difficulty is the issue of applicability of data from
      other countries to patients in our setting with different socio-economic factors.
      Other barriers to EBM in developing countries include: inexperience in small
      group learning, limited time to attend workshops, and the lack of role models for
      practicing EBM. We have also tried to address the common fallacies related to EBM
      in the hope of greater use of these skills by busy clinicians as well as academic
      researchers.

PMID- 18062523
TI  - Audit of an acute pain service in a tertiary care hospital in a developing
      country.
AB  - The first anaesthesia based acute pain service (APS) was introduced in Pakistan
      at the Aga Khan University Hospital in July 2001, with the aim of patient safety
      and satisfaction. The American Society of Anesthesiologist task force guidelines
      were used for the introduction of APS. APS has managed 6810 patients during four
      and half years period. Common analgesic techniques used, were intravenous
      infusion (50%), patient controlled intravenous analgesia (18%) and epidural
      infusions (30%). Common reported side effects were nausea and vomiting with
      intravenous infusion (10%) and PCIA (10%) while motor block was noticed with
      epidural infusion (29%). This article aims to share experience with the initial
      setup of APS, difficulties faced after establishment of APS and an audit to show
      overall APS performance.

PMID- 18062524
TI  - Mid aortic syndrome correction: anaesthetic considerations and management.
AB  - A twelve years old female patient presented with headache off and on and
      disparity between upper and lower limb pressures. On the basis of history,
      physical examination and magnetic resonance angiography, the patient was
      diagnosed as mid aortic syndrome and planned for elective aorto aortic bypass
      graft surgery through left thoracotomy. Double lumen endotracheal tube was placed
      for lung isolation and episodes of hypertension during proximal and distal cross
      clamp were controlled with sodium nitropruside infusion (SNP). Extra pleural
      catheter was put in at the end of surgery before chest wall closure for
      postoperative pain control. Both upper and lower limb pressures were monitored in
      the cardiac intensive care unit (CICU) and over a period of twenty four hours,
      gradient gradually reduced to 10 mm Hg.

PMID- 18062525
TI  - Epidural anaesthesia during labour for a patient with congenital complete heart
      block: a case report.
AB  - We report labour pain management in a full-term pregnant patient with Congenital
      Complete Heart Block. She delivered uneventfully under routine monitoring with
      facilities for pacing at hand. She previously had an uneventful normal delivery
      and a D&E, both outside our hospital. Only findings were a low heart rate of 45
      50 beats per minute. She never had syncopal attacks. She had a good effort
      tolerance on ETT. Her ejection fraction was 60% on Echocardiogram. She was given
      a single shot low dose spinal with fentanyl followed by epidural insertion. She
      successfully delivered through mid-cavity forceps in about 2.5 hours. The only
      problem encountered was a transient bradycardia of 40 per minute with a systolic
      blood pressure of 70 mmHg, which settled with ephedrine. Pace maker insertion is
      recommended early in case the patient is symptomatic or has a prolonged Q-T
      interval or left atrial enlargement on ECG. Regional anaesthesia is recommended
      to prevent valsalva induced bradycardia or cardiac arrest during expulsive
      efforts by the patient.

PMID- 18062526
TI  - Pulmonary tuberculosis in allogeneic stem cell transplant recipients.
AB  - Mycobacterium tuberculosis is a serious, but rare infectious complication after
      allogeneic bone marrow transplantation. Tuberculosis is a major problem in South
      East Asia, particularly in India and Pakistan. We describe here infection due to
      mycobacterium tuberculosis in four patients after allogeneic stem cell
      transplantation (Allo SCT). The diagnosis was made on the bases of clinical
      findings, sputum / blood / pleural and pericardial fluids / broncho alveolar
      lavage (BAL) and tissue biopsy examination. Anti tuberculosis therapy (ATT) was
      started immediately after diagnosis. Three patients responded to antituberculosis
      therapy, where as one patient developed severe infective respiratory
      complications and died at six months post transplant. Mycobacterial infection
      should be considered in patients post allo SCT with unexplained fever, cough or
      pleuritic chest pain. These patients at diagnosis should be promptly treated with
      ATT.

PMID- 18062527
TI  - Endoscopic sinus surgery of frontal mucocele.
AB  - The findings and symptoms associated with a mucocele depend on its location and
      on the extent of bony erosion. Men and women are affected equally, and these
      lesions are mostly encountered during the third and fourth decades of life. We
      describe a frontal mucocele that accompanied diplopia, headache, and displacement
      of orbita and was successfully managed by endoscopic sinus surgery and medical
      treatment.

PMID- 18062528
TI  - Why physicians should not have any contact with pharmaceutical companies?

PMID- 18062529
TI  - Competency assurance of general practitioners--role of regulatory authority.

PMID- 18062530
TI  - Pattern of glomerulonephritides in adult nephrotic patients--report from SIUT.

PMID- 18062531
TI  - Pre-operative renal function and selective renal vein renin levels as markers of
      favourable outcome in renovascular hypertension.

PMID- 18062532
TI  - Effects of verb complexity on speech errors.
AB  - Two experiments examined whether semantically related verbs that contrast with
      respect to the absence versus the presence of an additional semantic feature
      differentially compete for selection during the encoding of a sentence for
      production. In both experiments, a speech error induction task was used to elicit
      contextual (misordering) errors involving semantically related verbs that
      contrasted only in their semantic complexity or in both their semantic and
      morphophonological complexity. The prediction was that an asymmetry in contextual
      errors would be observed in which the more complex verbs would replace the
      simpler verbs more often than the reverse. This prediction was confirmed in both
      experiments, with more perseverations and anticipations involving the
      semantically more complex verb of antonym pairs in Experiment 1, and more
      perseverations and anticipations involving the semantically more-specified verb
      of a heavy-light pair in Experiment 2. The implications of the results for
      spreading-activation theories of language production are discussed.

PMID- 18062533
TI  - Cross-language message- and word-level transfer effects in bilingual text
      processing.
AB  - The present study examined the nature of the mental representations bilinguals
      form when reading a text and to what extent they are language specific. English
      French bilinguals read five pairs of passages in succession while their eye
      movements were tracked. Dependent measures were overall reading times on second
      passages and fixation latencies on target cognates embeddedin second passages.
      The first passage w as (1) identical tothe second passage in the pair, (2)
      related in content only (i.e., a translation), (3) related in content and some
      words (i.e., translation with cognates), (4) related in words only (i.e.,
      different content with the same cognates), or (5) unrelated. There was
      substantial cross-language facilitation for passages that shared meaning, but the
      amount of transfer was less than that for identical passages, indicating that
      memory representations are largely meaning based but do contain some information
      about surface form. Cross-language transfer for cognates was observed but
      depended on the skill of the bilinguals in their second language, the direction
      of transfer, and whether the passages shared meaning. These results are discussed
      in relation to Raney's (2003) model of text representation.

PMID- 18062534
TI  - Text repetition and text integration.
AB  - Two experiments explored the levels of text representation that mediate text
      repetition effects, following the Raney (2003) model. The magnitude of the
      repetition benefit in Experiment 1 supported predictions of Raney's model,
      indicating that the ease of forming a situation model contributed to the
      magnitude of the reprocessing benefit. In addition, representations organized
      around a good situation model were more sensitive to changes than were
      representations formed from reading without a good situation model. The results
      of Experiment 2 did not support the suggestion that the surface form and textbase
      are bound to a well-developed situation model, thereby limiting repetition
      effects to similar linguistic contexts. Rather, the nature of the repetition
      benefits in the present series of experiments are better explained by the degree
      o foverlap between passages at eachof the three levels of text representation.

PMID- 18062535
TI  - The effects of prior knowledge and text structure on comprehension processes
      during reading of scientific texts.
AB  - The aim of the present study was to investigate the effects of prior knowledge
      and text structure on cognitive processes during comprehension of scientific
      texts. To investigate the processes online, we used a think-aloud methodology in
      Experiment 1 and a reading time methodology in Experiment 2. In both experiments,
      we obtained offline comprehension measures and measures of individual differences
      in working memory and need for cognition. Across the two experiments, the results
      indicated that readers adjust their processing as a function of the interaction
      between prior knowledge and text structure. In particular, adjustments in
      theactual processes that take place during reading were observed for readers who
      had erroneous prior knowledge,but only when they read a text that was structured
      to explicitly refute this prior knowledge. Furthermore, the results showed that
      readers' memory for the text was affected by differences in their prior
      knowledge, independently of text structure. These findings contribute to our
      understanding of the relation between different factorsthat are associated with
      comprehension of scientific texts and have implications for theories of
      comprehension and conceptual change.

PMID- 18062536
TI  - The influence of multiple readings on the missing-letter effect revisited.
AB  - In searching for a target letter while reading, participants make more omissions
      when the target letter is embedded in frequent function words than when it is
      embedded in less frequent content words. According to the guidance-organization
      (GO) model, this occurs because high-frequency function words are processed
      faster than low-frequency content words, leaving less time available for letter
      processing. We tested this hypothesis in three experiments by increasing word
      processing speed through text repetition, which should translate into higher
      omission rates. Participants either read the text and searched for the target
      letter once or read the text three times and searched for a target letter on all
      readings or the final reading only. In all the experiments in which participants
      could not anticipate the target letter to be used, results revealed the presence
      of a large missing-letter effect that was unaffected by familiarity with the
      text. In addition, when participants knew from the start the target letter to be
      used on the final reading, the missing-letter effect was eliminated. Repeated
      search of the same text for different targets increased omissions equally for
      function words and content words, but this finding was present even when a new
      text was used, suggesting that repetition of the search task, rather than
      familiarity with the text, was responsible.

PMID- 18062537
TI  - Repeating phrases across unrelated narratives: evidence of text repetition
      effects.
AB  - Research has shown that text repetition effects are limited to conditions in
      which the context remains consistent across the two processing episodes,
      particularly when readers are focused on comprehension. Despite this, we found
      evidence of transfer effects across unrelated narratives. In a repeated
      condition, an ambiguous phrase appeared in two consecutive stories. In Story A,
      the phrase was presented in a sarcasm-biasing context, and in Story B, the phrase
      was presented in a neutral context. The pattern of findings from an offline
      measure (Experiment 1) and a reading time measure (Experiments 2, 3, and 4)
      indicated that participants were more likely to interpret the phrase in Story B
      as sarcastic in the repeated version than in a nonrepeated version, in which the
      phrase was absent from Story A. We conclude that during the reading of Story B,
      the phrase was reactivated from memory, even though the two stories were
      unrelated.

PMID- 18062538
TI  - Comparing decay rates for accurate and false memories in the DRM paradigm.
AB  - Although previous studies have consistently reported different forgetting rates
      for true and false memory when tested with recall, studies comparing the rates of
      decay for true and false recognition have reported inconsistent results. The
      present study attempted to clarify this inconsistency by comparing forgetting
      rates for true and false recognition in addition to addressing methodological
      differences among the previous studies. Recognition of list items and critical
      lures was assessed at six delays (2, 5, 10, 15, and 20 min, and 2 days). A
      comparison of power function slopes across item type provided evidence of slope
      differences such that false recognition decayed more quickly than true
      recognition, which is inconsistent with predictions from activation/ source
      monitoring and fuzzy tracetheories.

PMID- 18062539
TI  - Recognition without face identification.
AB  - Recognition without identification is the finding that participants can recognize
      recognition test items as having been previously studied when the test items
      themselves are presented in such a way that their identification is hindered. The
      present study demonstrates this phenomenon in face recognition. Participants
      studied names of celebrities before receiving a recognition test containing
      pictures of celebrity faces. Half of the pictures were of celebrities whose names
      were studied; half were of celebrities whose names were not studied. Participants
      attempted to identify each face on the test and also rated the likelihood that
      each person's name was studied. Among the faces that went unidentified, ratings
      discriminated between celebrities whose names were studied and celebrities whose
      names were not studied. This recognition without face identification effect is
      dependent upon the sense of being in a tip-of-the-tongue state for a particular
      name. Theoretical implications of the results are discussed.

PMID- 18062540
TI  - Environmental context effects of background color in free recall.
AB  - In four experiments, we investigated background-color context effects in free
      recall. A total of 194 undergraduates studied words presented one by one against
      a background color, and oral free recall was tested after a 30-sec filled
      retention interval. A signal for recall was presented against a background color
      throughout the test. Recalled items were classified as same- and different
      context items according to whether the background colors at study and test were
      the same or different. Significant context effects were found in Experiments I
      and 2, in which two background colors were randomly alternated word by word. No
      context effects were found in Experiments 3 and 4, in which a common background
      color was presented for all items (Experiment 3) or for a number of successive
      items (Experiment 4). The results indicate that a change in background colors is
      necessary and sufficient to produce context effects. Implications of the present
      findings are discussed.

PMID- 18062542
TI  - Memory for spatial location: cue effects as a function of field rotation.
AB  - We developed theoretical extensions of Huttenlocher, Hedges, and Duncan's (1991)
      category-adjustment model of human spatial memory to incorporate the use of fuzzy
      boundariesand cue-determined prototypes. In two experiments, people reproduced
      locations of dots in a circle, while the number of external reference cues
      varied. In Experiment 1, the task field was stable and results were consistent
      with the use of fixed categories unaffected by number of cues. In Experiment 2,
      the task field was made dynamic by rotation on most trials, with results
      evaluated for nonrotation trials. The large cue effects observed for angular bias
      were consistent with the proposed cue-based fuzzy-boundary model. Large cue
      effects were also observed for absolute error, consistent with a model in which
      proximity to cues predicts stability of memory. Results point to the key role of
      orientation to the task environment in determining whether categorical encoding
      is based on cues.

PMID- 18062541
TI  - Falsely recalled items are rich in item-specific information.
AB  - Current theorizing suggests that critical lures in the Deese/Roediger-McDermott
      (DRM) procedure are often falsely remembered because they have received
      considerable relational processing (e.g., spreading activation or encoding of
      gist information). We used a repeated-testing paradigm to assess the amount of
      item-specific and relational processing given to the list items and the critical
      lures. Research has shown that items receiving item-specific processing are more
      likely to be recovered across successive tests. They are also output more slowly
      but more steadily throughout the recall period. In two experiments, we
      manipulated the processing performed on list items and then used item gains and
      cumulative recall curves to assess the amount of item-specific an drelational
      information encoded for both list items and lures. The results suggest that
      increasing the relational processing of list items increased item-specific
      processing of lures, whereas increasing item-specific processing of list items
      decreased item-specific processing of lures. We conclude that critical lures are
      typically rich in item-specific information, relative to list items.

PMID- 18062543
TI  - Olfaction and emotion: the case of autobiographical memory.
AB  - This study investigated (1) the influence of verbal and conceptual processing on
      the retrieval and phenomenological evaluation of olfactory evoked memories, and
      (2) whether the experienced qualities of retrieved information are affected by
      olfactory exposure per se. Seventy-two older adults were randomized into one of
      three cue conditions (odor only, name only, or odor name) and asked to relate any
      autobiographical event for the given cue. The results indicated that semantic
      knowledge of an odor's name significantly affects the age distribution of
      memories such that the memory peak in childhood observed for odors only was
      attenuated. Also, experiential factors such as pleasantness and feelings of being
      brought back in time were lower when odors were presented with their respective
      names. Olfactory evoked memories were associated with a higher emotional arousal
      that could not be accounted for by the perceptual stimulation alone. Taken
      together, the overall pattern of findings suggests that retrieval of olfactory
      evoked information is sensitive to semantic and conceptual processing, and that
      odor-evoked representations are more emotional than memories triggered by verbal
      information.

PMID- 18062544
TI  - Memory for scenes: refixations reflect retrieval.
AB  - Most conceptions of episodic memory hold that reinstatement of encoding
      operations is essential for retrieval success, but the specific mechanisms of
      retrieval reinstatement are not well understood. In three experiments, we used
      saccadic eye movements as a window for examining reinstatement in scene
      recognition. In Experiment 1, participants viewed complex scenes, while number of
      study fixations was controlled by using a gaze-contingent paradigm. In Experiment
      2, effects of stimulus saliency were minimized by directing participants' eye
      movements during study. At test, participants made remember/know judgments for
      each recognized stimulus scene. Both experiments showed that remember responses
      were associated with more consistent study-test fixations than false rejections
      (Experiments 1 and 2) and know responses (Experiment 2). In Experiment 3, we
      examined the causal role of gaze consistency on retrieval by manipulating
      participants' expectations during recognition. After studying name and scene
      pairs, each test scene was preceded by the same or different name as during
      study. Participants made more consistent eye movements following a matching,
      rather than mismatching, scene name. Taken together, these findings suggest that
      explicit recollection is a function of perceptual reconstruction and that event
      memory influences gaze control in this active reconstruction process.

PMID- 18062545
TI  - The effects of processing time and processing rate on forgetting in working
      memory: testing four models of the complex span paradigm.
AB  - Four models of working memory processes in the complex span paradigm were tested:
      The task-switching model of Towse, Hitch, and Hutton (1998), the interference
      account of Saito and Miyake (2004), and two versions of the time-based resource
      sharing model of Barrouillet, Bernardin, and Camos (2004). On the basis of a
      reading span paradigm that used segmented sentences, the effect of processing
      time on the recall of words was investigated while the amount of processing was
      held constant. Two conditions of reading (continuous vs. normal) were compared in
      order to study the influence of brief pauses during reading that could be used
      for articulatory rehearsal. The results favor a version of the time-based
      resource-sharing model: A faster reading rate had a negative effect on recall.
      The effect of reading rate was obtained with continuous as well as normal
      reading, revealing that even continuous articulation does not prevent
      simultaneous refreshing of memory traces. A second experiment showed that
      continuous reading made concurrent articulatory rehearsal virtually impossible.
      These findings imply that a second rehearsal mechanism for verbal working memory,
      other than articulatory rehearsal, exists.

PMID- 18062546
TI  - Evidence for parallel semantic memory retrieval in dual tasks.
AB  - In this dual-task study, we applied both cross-talk logic and locus-of-slack
      logic to test whether participants can retrieve semantic categories in Task 2 in
      parallel to Task 1 bottleneck processing. Whereas cross-talk logic can detect
      parallel memory retrieval only in conditions of categorical overlap between
      tasks, the locus-of-slack approach is independent of such restrictions. As was
      expected, using the cross-talk logic, we found clear evidence for parallel
      retrieval of semantic categories when there was categorical overlap between tasks
      (Experiment 1). Locus-of-slack-based evidence for parallel semantic retrieval was
      found, however, both in conditions with (Experiment 1) and in those without
      (Experiment 2) categorical overlap between tasks. Crucially,however, increasing
      the demand for resources required to switch from Task 1 to Task 2 eliminated even
      the locus-of-slack-based evidence for parallel memory retrieval during the
      psychological refractory period (Experiment 3). Together, our results suggest
      that parallel retrieval is not bound to conditions of categorical overlap between
      tasks but, instead, is contingent upon resources needed for switching between
      tasks (e.g., Oriet, Tombu, & Jolicoeur, 2005).

PMID- 18062547
TI  - Associative processes in immediate recency.
AB  - Some theorists have argued that the immediate recency effect observed in free
      recall reflects the emptying out of the contents of a short-term memory buffer
      (Davelaar, Goshen-Gottstein, Ashkenazi, Haarmann, & Usher, 2005). Others have
      argued that immediate recency reflects the properties of temporal context used to
      cue free recall (Howard & Kahana, 2002). We examined immediate free recall of
      lists with an item from the middle of the list repeated at or near the end. If
      associative processes contribute to immediate recency, as predicted by the
      temporal context account, the neighbors of the initial presentation of the
      repeated item should show enhanced recall at the initial stages of immediate
      recall. Recall transitions early in output--and even the initiation of recall
      itself-showed evidence for temporally defined associations that resemble those
      observed in recall from long-term memory. These results have strong implications
      for models of the immediate recency effect in free recall.

PMID- 18062548
TI  - A role for action knowledge in visual object identification.
AB  - We evaluated the impact of visual similarity and action similarity on visual
      object identification. We taught participants to associate novel objects with
      nonword labels and verified that in memory visually similar objects were confused
      more often than visually dissimilar objects. We then taught participants to
      associate novel actions with nonword labels and verified that similar actions
      were confused moreoften th an dissimilaractions. We then paired specific objects
      with specific actions. Visually similar objects paired with similar actions were
      confused more often in memory than when these same objects were paired with
      dissimilar actions. Hence the actions associated with objects served to increase
      or decrease their separation in memory space, and influenced the ease with which
      these objects could be identified. These experiments ultimately demonstrated that
      when identifying stationary objects, the memory of how these object were used
      dramatically influenced the ability to identify these objects.

PMID- 18062549
TI  - Short-term recognition memory for serial order and timing.
AB  - Recent evidence suggests that a common temporal representation underlies memory
      for serial order of items in a sequence, and the timing of items in a sequence.
      This stands in contrast to other data suggesting a reliance on only ordinal
      information in short-term memory tasks. An experiment is reported here in which
      participants were post cued to perform a comparison between a probe and study
      list of items irregularly spaced in time, on the basis of order or temporal
      information.Participants' performance on theserial recognition task was
      notaffected by the temporal proximity of items, although participants were able
      to use temporal information to perform a temporal recognition task. Application
      of a temporal matching model of serial and temporal recognition suggests that
      although participants were able to remember the timing of items, this memory for
      timing was unlikely to determine serial recognition performance. The results
      suggest a dissociation between ordinal and temporal information in short-term
      memory.

PMID- 18062550
TI  - Realizing complex delayed intentions in young and old adults: the role of
      planning aids.
AB  - Although it has been suggested that the delayed realization of intended actions
      should benefit from appropriate intention planning, empirical evidence on this
      issue is scarce. In three experiments, we examined whether and which planning
      aids provided in the intention formation phase affect delayed intention
      realization in young and old adults. One finding was that intention planning
      directly affected delayed intention realization: instructing participants to
      include the cue for appropriate intention initiation in their plans benefited
      delayed performance. Another finding was that older adults' performance was
      improved when they were guided in structuring their plan in combination with
      guidance in implementing this plan after a delay. In sum, the results point to
      the importance of plan-related factors for understanding the delayed realization
      of intended actions.

PMID- 18062551
TI  - Feedback interference and dissociations of classification: evidence against the
      multiple-learning-systems hypothesis.
AB  - Researchers have argued that different categorization problems are learned by
      separate and distinct cognitive systems. They propose that an explicit system is
      responsible for learning rule-based categories and that a separate implicit
      system learns information-integration categories. One source of supporting
      evidence involves experiments in which observers perform a concurrent memory
      scanning task that interferes with the processing of feedback. Researchers have
      reported a dissociation in which this manipulation impairs learning of a rule
      based category but not an information-integration category. In the present
      research, we test the hypothesis that the dissociation was the result of lowered
      perceptual discriminability in the rule-based structure in comparison with the
      information-integration one. We demonstrate an example of an alternate rule-based
      category with easy-to-discriminate stimuli in which performance is unaffected by
      the interfering memory-scanning task. Furthermore, we demonstrate that learning
      of an information-integration category with low perceptual discriminability is
      impaired by the memory-scanning task. These demonstrations of the reverse
      dissociation challenge the interpretation that rule-based and information
      integration category structures are learned by separate cognitive systems.

PMID- 18062552
TI  - Do multiplication and division strategies rely on executive and phonological
      working memory resources?
AB  - The role of executive and phonological working memory resources in simple
      arithmetic was investigated in two experiments. Participants had to solve simple
      multiplication problems (e.g., 4 x 8; Experiment 1) or simple division problems
      (e.g., 42 / 7; Experiment 2) under no-load, phonological-load, and executive-load
      conditions. The choice/no-choice method was used to investigate strategy
      execution and strategy selection independently. Results for strategy execution
      showed that executive working memory resources were involved in direct memory
      retrieval of both multiplication and division facts. Executive working memory
      resources were also involved in the use of nonretrieval strategies. Phonological
      working memory resources, on the other hand, tended to be involved in
      nonretrieval strategies only. Results for strategy selection showed no effects of
      working memory load. Finally, correlation analyses showed that both strategy
      execution and strategy selection correlated with individual-difference variables,
      such as gender, math anxiety, associative strength, calculator use, arithmetic
      skill, and math experience.

PMID- 18062553
TI  - Thinking about conditionals: a study of individual differences.
AB  - Recent studies have shown the existence of two qualitatively distinct groups of
      people based on how they judge the probability of a conditional statement. The
      present study was designed to test whether these differences are rooted in
      distinctive means of processing conditional statements and whether they are
      linked to differences in general intelligence. In the study, each of 120
      participants completed three separate cognitive tasks involving the processing of
      abstract conditional statements--the probability-of-conditionals task, the
      conditional truth table task, and the conditional inference task--in addition to
      completing a test of general intelligence (AH4). The results showed a number of
      predicted effects: People responding with conditional (rather than conjunctive)
      probabilities on the first task were higher in cognitive ability, showed
      reasoning patterns more consistent with a suppositional treatment of the
      conditional, and showed a strongly "defective" truth table pattern. The results
      include several novel findings and post challenges to contemporary psychological
      theories of conditionals.

PMID- 18062554
TI  - Metamorphosis: essence, appearance, and behavior in the categorization of natural
      kinds.
AB  - The transformation paradigm (Rips, 1989) was used to contrast causal homeostasis
      and strict essentialist beliefs about biological kinds. Participants read
      scenarios describing animals that changed their appearance and behavior through
      either accidental mutation or developmental maturation and then rated the animals
      on the basis of similarity, typicality, and category membership both before and
      after the change. Experiment 1 in the present study replicated the dissociation
      of typicality and categorization reported by Rips (1989) but also revealed
      systematic individual differences in categorization. With typicality and
      membership ratings collected between participants, however, Experiment 2 found no
      evidence for the dissociation and few essentialist responders. In Experiment 3,
      excluding information about offspring led most participants to categorize on the
      basis of appearance and behavior alone. However, with offspring information
      included and with questioning focused on the change of kind, essentialist
      categorization was still surprisingly rare. We conclude that strict essentialist
      categorization in the transformation task is relatively rare and highly task
      dependent, and that categorization is more commonly based on causal homeostasis.

PMID- 18062555
TI  - The influence of information redundancy on probabilistic inferences.
AB  - Information redundancy affects the accuracy of inference strategies. A simulation
      study illustrates that under high-information redundancy simple heuristics that
      rely on only the most important information are as accurate as strategies that
      integrate all available information, whereas under low redundancy integrating
      information becomes advantageous. Assuming that people exercise adaptive strategy
      selection, it is predicted that their inferences will more often be captured by
      simple heuristics that focus on part of the available information insituations
      ofhigh-information redundancy, especially when information search is costly. This
      prediction is confirmed in two experiments. The participants' task was to
      repeatedly infer which of two alternatives, described by several cues, had a
      higher criterion value. In the first experiment, simple heuristics predicted the
      inference process better under high-information redundancy than under low
      information redundancy. In the second experiment, this result could be
      generalized to an inference situation in which participants had no prior
      opportunity to learn about the strategies' accuracies through outcome feedback.
      The results demonstrate that people are able to respond adaptively to different
      decision environments under various learning opportunities.

PMID- 18062556
TI  - Categorical perception of facial expressions: evidence for a "category
      adjustment" model.
AB  - Four experiments probed the nature of categorical perception (CP) for facial
      expressions. A model based on naming alone failed to accurately predict
      performance onthese tasks. The data are instead consistentwith an extension of
      the category adjustment model (Huttenlocher et al., 2000), in which the
      generation of a verbal code (e.g., "happy") activated knowledge ofthe expression
      category's range andcentral tendency (prototype) in memory, which was retained as
      veridical perceptual memory faded.Further support for amemory bias toward the
      category center came from a consistently asymmetric pattern of within-category
      errors. Verbal interference in the retention interval selectively removed CP for
      facial expressions, under blocked, but not under randomized presentation
      conditions. However, verbal interference at encoding removed CPeven under
      randomized conditions and these effects were shown to extend even to caricatured
      expressions, which lie outside the normal range of expression categories.

PMID- 18062557
TI  - How many processes underlie category-based induction? Effects of conclusion
      specificity and cognitive ability.
AB  - Two studies investigated participants' sensitivity to the amount and diversity of
      the evidence when reasoning inductively about categories. Both showed that
      participants are more sensitive to characteristics of the evidence for arguments
      with general rather than specific conclusions. Both showed an association between
      cognitive ability and sensitivity to these evidence characteristics, particularly
      when the conclusion category was general. These results suggest that a simple
      associative process may not be sufficient to capture somekey phenomena of
      category-based induction. They also support the claim that the need to generate a
      superordinate category is a complicating factor in category-based reasoning and
      that adults' tendency to generate such categories while reasoning has been
      overestimated.

PMID- 18062558
TI  - Should all patients with type 2 diabetes receive initial combination therapy: an
      assessment of the ADVANCE trial.

PMID- 18062559
TI  - New European guidelines for the management of patients with unstable angina/non
      ST-elevation myocardial infarction--what are the new and key messages.

PMID- 18062560
TI  - What are the practical implications of current data on the worldwide prevalence
      of COPD?

PMID- 18062561
TI  - Relationship of the patient age and intensity of type 2 diabetes treatment.
AB  - INTRODUCTION: Analysis of results of research on aging indicates that negative
      stereotypes about diminished needs and abilities to achieve satisfaction in
      elderly have negative impact on well-being of persons in late adulthood. These
      negative stereotypes are shared by older people and the other members of society,
      including physicians. However, only few research on the impact of negative
      stereotypes on the way of older patients treatment have been done. OBJECTIVES: To
      verify a hypothesis that elderly patients with type 2 diabetes are treated less
      intensively than younger patients. PATIENTS AND METHODS: The method of treatment
      was analyzed in two groups of patients. The first group contained 1199 patients
      aged 17-93 years, treated for a period of less than one year to 36 years, that
      were beginning insulin therapy. The second group contained 1693 patients aged 22
      97 years, treated for the less than one year till 70 years, that were beginning
      treatment with insulin analogues. RESULTS: The moderate negative correlation
      between an age and treatment intensiveness measured as a number of injections per
      day was found (r = -0.253; p < 0.01), as well as the lower average age in groups
      of patient receiving more injections of insulin a day (post-hoc Least Significant
      Difference test: F(891.3) = 25.21; p < 0.0001). The mean age of patients
      intensively treated with analogues of insulin was lower than those treated less
      intensively (57.9 vs. 63.4, respectively; t-Student test: t = 8.36, p < 0.0001).
      CONCLUSIONS: The older patients with type 2 diabetes received less intensive
      treatment than the younger. The stereotype of overestimation of the decrease of
      cognitive abilities in aging and eventually of difficulties in adherence to more
      complex by older people may be a reason of their undertreatment.

PMID- 18062562
TI  - Prevalence of COPD and tobacco smoking in Malopolska region--results from the
      BOLD study in Poland.
AB  - INTRODUCTION: There is a paucity of population-based data on chronic obstructive
      pulmonary disease (COPD) prevalence in Poland. To address this problem we
      participated in the Burden of Obstructive Lung Disease (BOLD) Initiative which
      was developed to provide standardized methods for estimating the prevalence of
      COPD and its risk factors. OBJECTIVES: The study aimed to assess the prevalence
      of COPD and some of its risk factors in adults aged 40 years and older in the
      Malopolska region in southern Poland. PATIENTS AND METHODS: Region-
      representative sample was drawn, basing on the current census data. Detailed BOLD
      questionnaires as well as pre- and post-bronchodilator spirometry were applied to
      eligible individuals. RESULTS: Six hundred and three subjects provided
      questionnaire and spirometry data; of those 526 provided spirometry data of
      appropriate quality and were included in the final analysis. Estimated population
      prevalence of COPD was 22.1%, whereas 10.9% had COPD in GOLD Stage > or = 2. COPD
      was far more common in men and its prevalence increased with age and exposure to
      tobacco smoke, and was inversely related to education level. The prevalence of
      current tobacco smoking was 28% (34% and 22% in men and women, respectively).
      Seventy-nine percent of men and 42% of women were ever-smokers. Twenty-nine
      percent of never smoking individuals were passively exposed to tobacco smoke in
      their households. CONCLUSIONS: Our results confirm the high prevalence of COPD in
      the studied region of Poland and emphasize the need to increase efforts to
      improve COPD awareness and limit tobacco smoking habit.

PMID- 18062564
TI  - [Inhaled insulin--the breakthrough in the treatment of diabetes?].
AB  - Diabetes as a global epidemic is the fourth cause of death in the world
      currently. Ninety percent of all cases of diabetes represent patients with type 2
      diabetes, in whom worsening of glycaemic control is observed with progression of
      the disease. A number of trials which have been conducted so far showed that lack
      of sufficient glycaemic control in both type 1 and type 2 diabetic patients
      accelerates progression of late complications of the disease. Although targets
      how to treat diabetes have been clearly defined few patients achieve them and
      maintain optimal metabolic control. Administration of insulin in type 1 diabetes
      is crucial for survival of the patients. Because of progressive course of the
      disease insulin is not rarely the only tool to achieve full normalization of
      glycaemia in type 2 diabetic patients. Chronic hyperglycemia in type 2 diabetic
      patients is the main reason to start insulin therapy. Decision about insulin
      administration is usually associated with patient's confusion and fear, mainly
      because of multiple subcutanoeus injections and risk of hypoglycaemia or
      secondary weight gain. Studies on inhaled insulin have been successfully
      completed recently. In the spring of 2005 Exubera, the first insulin inhaler, has
      been registered. The aim of this overview is to present the current clinical data
      on Exubera in treatment of patients with type 1 and 2 diabetes.

PMID- 18062563
TI  - [Proteinuria as a predictor of risk of cardiovascular disease: a new insight].
AB  - Mortality and morbidity due to cardiovascular disease is one of the fundamental
      health problems at present. Proteinuria is not only commonly recognized factor of
      progression of chronic renal diseases, but is also independent risk factor for
      cardiovascular complications. Lately, the value of albuminuria as a prognostic
      factor in the course of cardiovascular diseases has increased its significance.
      Not long ago, there was considered that only microalbuminuria (quantity of
      excreted albumins in urine above 30 to 300 mg daily) indicates on increased risk
      of complications of such diseases as arterial hypertension or diabetes. However,
      observational studies, as well as interventional studies lead us to verify that
      view. It turned out that in the general population the number of cardiovascular
      complications leading to death increases in proportion to the quantity of
      albumins excreted in urine. Moreover, it was found that the relationship is
      continuous in a wide range of albuminuria even at value below the lower limits
      accepted now as normal levels, i.e., 30 mg per day corresponding with urinary
      albumin concentration 20 mg/L. It means that not only the quantity of excreted
      albumins but also the presence of albumin in urine indicate a higher risk of
      cardiovascular death. It may be assumed therefore that the presence of albumin in
      urine gives the evidence of unfavorable functional state of the circulatory
      system followed by fatal consequences. Therefore, the presence of albuminuria
      ought to be considered in quality and quantity aspects.

PMID- 18062565
TI  - [Statins--are they potentially useful in rheumatology?].
AB  - For more than 30 years statins have been successfully used in patients with
      hypercholesterolemia and cardiovascular diseases. Recently, there is a growing
      body of evidence, that statins exert effects by much exceeding the effect of
      cholesterol level decrease. Inhibition of earlier stages of cholesterol
      biosynthesis pathway (not influencing the very cholesterol level) results in
      blocking the intermediate metabolite synthesis; isoprenoids (farnesyl phosphate
      and geranyl phosphate), which play a regulatory function in cells. Statins have
      antiatherosclerotic, antiinflammatory, antioxidant, immunomodulatory and
      antithrombotic effects. It applies equally to diseases of chronic inflammation
      type, as to those, where bone metabolism is disturbed. It is well known that
      statins decrease bone fracture risk; through bone formation intensification, and
      inhibition of bone tissue resorption. Slowing down the atherosclerosis
      progression is a very important effect, considering that in rheumatoid arthritis
      (RA) and in systemic lupus erythematosus (SLE) we are dealing with premature and
      rapid progression of atherosclerotic lesions. In this paper statins pathways of
      action in rheumatic diseases (including pleiotropic effects), and their potential
      use in rheumatology have been discussed. Though there is lack of reliable data
      enabling statins introduction to standard complementary therapy in rheumatic
      diseases, the results however of completed studies allow concluding of their
      utility. The statins that were most frequently evaluated in clinical studies were
      simvastatin and atorvastatin. Studies on statins have been performed in RA, SLE,
      osteoporosis and systemic vasculotos.

PMID- 18062566
TI  - [Behcet's disease--diagnostic difficulties].
AB  - Behcet's disease, rare in Poland, has been described in a 47-year-old woman with
      mucocutaneous lesions and gynecological pathology, persisting for 4 years before
      establishing the correct diagnosis. The criteria, course and principles of
      treatment were reminded in hope it may be useful for the physicians of various
      specialities.

PMID- 18062567
TI  - [Tuberculosis treatment in Poland at the turn of 20th century (till 1914)].
AB  - At the turn of 20th century on Polish territory tuberculosis was treated like in
      western European countries with conservative--symptomatic methods
      (climatotherapy, using dietetherapy) and invasive methods (emphysema,
      thoracoplasty). In fight against tuberculosis dr Seweryn Sterling stood out from
      all the Polish doctors at that time.

PMID- 18062568
TI  - Oklahoma Medicaid program offers a decade's worth of insights.

PMID- 18062569
TI  - NCQA adds value to its quality agenda.

PMID- 18062570
TI  - [The patient is concerned, you also? Look into my eyes!].

PMID- 18062571
TI  - [Of "illness inducers" and "feel good medicine". Can one still be a good
      physician today?].

PMID- 18062572
TI  - [Steroids in rheumatoid arthritis. Advantages and disadvantages in their use?].

PMID- 18062573
TI  - [More colorectal cancer patients could be saved].

PMID- 18062574
TI  - [Principles and quality control of surgical therapy of rectal carcinoma].
AB  - During the past years, it has been possible to achieve impressive success in the
      treatment of rectal carcinoma through standardized therapeutic concepts. Through
      the consistent application of total mesorectal excision (TME) as a therapeutic
      procedure, a dramatic improvement in local recurrence rate has been attained.
      Future strategies are now aimed at improving postoperative quality of life and
      moreover, at reducing the incidence of distant metastasization. The positive
      development during recent years is ultimately also the result of increasing
      quality control. Hence, surgery with its specific quality criteria has been
      integrated into a broad spectrum of various individual factors that must be taken
      into consideration in a multimodal therapeutic concept.

PMID- 18062575
TI  - [Neoadjuvant and adjuvant radiochemotherapy for rectal carcinoma].
AB  - The current standard treatment for resectable tumours in clinical stages II and
      III is neoadjuvant radio(chemo)therapy. Improved radiation techniques and
      chemotherapy (CT) with continuous infusion of 5-FU during adjuvant radiotherapy
      (RT) has led to an additional improvement of adjuvant therapeutic results. The
      efficacy of new cytostatic drugs and antibodies is presently being clinically
      tested for perioperative therapy.

PMID- 18062577
TI  - [Patient information. Colorectal cancer].

PMID- 18062576
TI  - [Systemic therapy of colorectal carcinoma].
AB  - The therapeutic strategy for colorectal carcinoma is based upon the UICC stage.
      For stages 0 and I, endoscopic and operative methods are available. For stage II
      colon cancer, the indication for adjuvant chemotherapy has not been verified. On
      the other hand, beginning with stage III, the benefit of this therapy for lymph
      node metastases is undisputed. Although neoaduvant therapy is not indicated for
      colon cancer, it is standard procedure for rectal carcinoma in this stage. The
      objective of palliative chemotherapy in UICC stage IV is to extend the quality of
      life.

PMID- 18062578
TI  - [Therapy with recombinant growth hormone].
AB  - Therapy with recombinant growth hormone is currently approved for the indications
      growth hormone deficiency,Turner syndrome, chronic renal failure, small for
      gestational age (SGA) and Prader-Willi syndrome. Positive experience from on
      going clinical studies (e.g. on obesity, type 2 diabetes, Crohn's disease)
      support an extended range of applications for recombinant growth hormone.
      However, growth hormone therapy is very expensive. On the other hand, biosimilars
      are already available that are significantly lower in price. During the coming
      years, research must show whether the efficacy and safety of biosimilars
      (including possible new indications) are equal to that of the established
      preparations.

PMID- 18062579
TI  - [Hypertension therapy for type 2 diabetics].

PMID- 18062580
TI  - [With laxatives and bloodletting against the minor pest].

PMID- 18062581
TI  - [Solid euros instead of soft points].

PMID- 18062582
TI  - [In GOA settlement do not omit: additions, case fees, expenses...].

PMID- 18062583
TI  - Na+/Mg2+ antiport in non-erythrocyte vertebrate cells.
AB  - Experiments, results and conclusions on Na+/Mg2, antiport in lymphocytes, HL60
      cells, Ehrlich ascites tumor cells, platelets, pancreatic acinar cells,
      sublingual acini, hepatocytes, ruminal epithelial cells, kidney cells, smooth
      muscle cells, heart muscle cells and skeletal muscle cells were reviewed. Only in
      a few experiments was the Mg2+ efflux via the Na+/Mg2+ antiport studied directly
      by measuring the alterations in [Mg2+]o and intracellular Na+ content. In most
      cell types, the Na+/Mg2+ antiport was investigated indirectly by measuring
      [Mg2+], and [Na+]i after changing the physiological Mg2+ homeostasis by effectors
      or by loading the cells with Mg2+. The effects of inhibitors and incubation in
      Na+ -free medium on the alterations in [Mg2+]i and [Na+]i were taken as evidence
      of the Na+/Mg2+ antiport. By these methods, the Na+/Mg2+ antiport was found in
      all investigated mammalian cell types. As far as they have been studied, the
      kinetic properties and regulation of Na+/Mg2+ antiport are reviewed.

PMID- 18062584
TI  - Magnesium ions and ionic channels: activation, inhibition or block--a hypothesis.
AB  - The interactions between magnesium ions and ionic membrane channels are
      complicated and may be classified in three categories: activation, reduction and
      inhibition of the ionic fluxes across the channels, corresponding to three
      mechanisms: open-block-close. The interactions between magnesium ions and various
      ionic channels are reviewed and the explanations of the three mechanisms are
      analyzed in term of screening/binding effects on the membrane surface polar head
      groups.

PMID- 18062585
TI  - Magnesium physiology and pathogenic mechanisms that contribute to the development
      of the metabolic syndrome.
AB  - The clinical and public health impact of the metabolic syndrome (MetS) has
      increased substantially in recent years. MetS is defined by a constellation of
      cardiovascular disease risk factors including: insulin resistance, elevated blood
      pressure, impaired glucose tolerance, central obesity, and atherogenic
      dyslipidemia as well as impaired clotting, increased inflammatory burden, and
      oxidative stress. Recently, there has been burgeoning experimental, clinical, and
      epidemiological data that provides strong evidence that dietary magnesium intake
      and supplementation are inversely associated with the risk for MetS and its
      components. In this review, we describe and discuss the myriad of integrated
      physiological mechanisms through which magnesium deficiency and the resultant
      altered magnesium status may lead to the development of the MetS and each of its
      components.

PMID- 18062587
TI  - Contents of bioelements and toxic metals in the Polish population determined by
      hair analysis. Part IV. Adults aged 40 to 60 years.
AB  - The aim of this study was to define referential values of 5 basic bioelements
      (Ca, Mg, Zn, Cu, Fe) and 2 toxic metals (Pb and Cd) in the hair of Polish adults
      aged 40 to 60 years, based on the research conducted from 1991 to 2006 on a group
      of 3349 formally healthy women and men. The results of our biochemical tests were
      subjected to statistical analysis and they can be treated as referential norms
      for the concentrations of analyzed bioelements in the hair of Polish population.
      Our analyses confirm significant differences in accumulations of certain elements
      (Ca, Mg, Zn) in women's and men's hair. The hair element analysis of the tested
      women population indicates the age 49-50 as the one in which a significant
      decrease of hair Ca and Zn begins. Marked decrease of Ca and Zn in men begins 2-3
      years later than in women. A slight tendency to decrease hair Mg in women and men
      during the period observed of 40-60 years of age was noticed. Significant
      differences (alpha = 0.05) between hair Cu contents in women and men were not
      observed. The increase of variances of hair Fe concentrations in women,
      especially after 50, has been observed. Significantly higher hair Pb and Cd
      concentrations were shown in men. The analysis of correlation confirms the
      significance (p < 0.050000) of synergistic interactions between bioelements: Ca
      Mg (r = +0.7635), Ca-Zn (r = +0.36), Ca-Cu (r = +0.124), Ca-Fe (r = +0.054), Mg
      Zn (r = +0.35), Mg-Cu (r = +0.11), Mg-Fe (r = +0.0757), Zn-Cu (r = +0.11), Cu-Fe
      (r = +0.0765). Significance (p < 0.050000) of antagonistic interactions of
      bioelements with toxic metals: Ca-Pb (r = -0.0965), Zn-Pb (r = -0.2476), Mg-Pb (r
      = -0.13), Zn-Cd (r = -0.0889) was established. Significance (p < 0.050000) of
      synergistic effects with toxic metals: Pb-Cd (r = +0.3322), Cu-Pb (r = +0.09), Fe
      Pb (r = +0.1413), Fe-Cd (r = +0.1161) was confirmed. Adults in whose hair
      bioelements and hair toxic metal concentrations have shown values outlying from
      reference and who have too much toxic elements and too little bioelements should
      undergo further diagnostic tests since these results could be a sign of
      disturbances, that could lead to various diseases.

PMID- 18062586
TI  - Hypocalcaemia may reduce the beneficial effect of magnesium treatment in
      aneurysmal subarachnoid haemorrhage.
AB  - To assess whether magnesium treatment in patients with subarachnoid haemorrhage
      (SAH) is associated with hypocalcaemia and whether hypocalcaemia in these
      patients is associated with an increased risk of delayed cerebral ischemia (DCI)
      and poor outcome. All 137 patients randomized in the clinically controlled
      "Magnesium in Aneurysmal Subarachnoid Haemorrhage" trial were included. The
      relationship between mean serum magnesium and mean serum calcium during treatment
      was assessed with linear regression. The relationship between hypocalcaemia
      (serum calcium < 2.0 mmol/L) during treatment and the occurrence of DCI and poor
      outcome was studied with the Cox proportional hazards method and logistic
      regression, respectively. There was a statistically significant inverse relation
      between elevated serum magnesium and hypocalcaemia (B = -0.27; 95% CI, -0.33 to 
      0.20; p < 0.001). Patients with hypocalcaemia during study treatment had an
      increased frequency of DCI (HR 2.1; 95% CI, 1.0 to 4.3), and an increased risk
      for poor outcome (OR 2.9; 95% CI, 1.4 to 6.4), but this effect attenuated in the
      multivariable analysis (OR 1.9; 95% CI, 0.8 to 4.7). In conclusion, prolonged
      elevated serum magnesium is associated with hypocalcaemia. Hypocalcaemia is
      associated with an increased risk of DCI and poor outcome and may therefore
      reduce the potential beneficial effect of magnesium treatment in SAH.

PMID- 18062588
TI  - Effect of a low magnesium diet on magnesium status and gene expression in the
      kidneys of mice selected for high and low magnesium erythrocyte levels.
AB  - The magnesium concentrations in plasma and cells could be affected by diet,
      disease and genetic factors. To characterise the genetic factors involved in the
      regulation of magnesium homeostasis, Low (MgL) and High (MgH) magnesium status
      mice were developed by bidirectional selective breeding. The effects of a low
      magnesium diet on the magnesium status parameters were analysed in these mice.
      Using a cDNA array, a screen for differential gene expression was performed in
      kidneys from these animals, fed either a magnesium adequate or deficient diet.
      The magnesium-deficient diet significantly affected the plasma, erythrocyte and
      urine magnesium concentrations in'both strains, in similar proportions in the two
      strains. Furthermore, in response to the magnesium-deficient diet, both strains
      showed changes of the expression of genes belonging, for the majority of them, to
      the family of transcription and growth factors (down-regulated). Of the
      identified genes, five were of particular interest because they were differently
      expressed in response to the deficient diet in these two strains: osteopontin,
      the cholecystokinin A receptor, connexin 45, a growth hormone receptor and BAG1.
      These results suggest that the two strains exhibit different physiopathological
      responses to magnesium deficiency.

PMID- 18062589
TI  - [Spondylodiscitis as cause of unexplained fever].
AB  - An 83-year-old woman was admitted to hospital with complaints of fever, abdominal
      pain and other complaints suggesting urosepsis. Additional analyses did not
      reveal the cause of her complaints. After cessation of antibiotic therapy, there
      was a spontaneous decrease in the infection parameters and she was subsequently
      discharged. Two and a half months later she was presented in our hospital with
      low back pain with radiating to the legs. MRI showed signs ofa spondylodiscitis
      at the level of LIII-LIV existing for some time. Finally, a gram-positive
      streptococcus infection was found and she was treated with antibiotics for 13
      weeks. 6 months later she was free of symptoms. A 57-year-old man was admitted to
      the intensive care with a double-sided olecranon bursitis and sepsis. An
      endocarditis caused by Staphylococcus aureus was thought to be the cause of the
      sepsis and the patient was treated with surgical intervention and antibiotics.
      Because of persistent sepsis, different CT-scans were performed, and after one
      and a half months an extensive spondylodiscitis with abscess formation was
      diagnosed and subsequently treated surgically. A delay in diagnosing
      spondylodiscitis is the rule rather the exception. The diagnosis should be
      considered in any patient with localised back pain, especially when accompanied
      by fever, high ESR, and the presence of risk factors such as high age, diabetes
      mellitus, immunosuppression, and/or rheumatoid arthritis.

PMID- 18062590
TI  - [Prevention of postoperative pulmonary complications by preoperative training].
AB  - Postoperative pulmonary complications are the main cause of morbidity and
      mortality after surgery. A likely explanation is dysfunction of the respiratory
      muscles, in particular the diaphragm, which results in rapid, shallow breathing
      and ultimately-in closing of the airways, atelectasis and hypoxaemia. Breathing
      exercises in the perioperative period, despite a good rationale, were in general
      not found to be effective. A promising new approach is specific training of
      inspiratory muscles. A randomized clinical trial, published in this issue of the
      journal, found this to be effective in patients at increased risk for
      postoperative complications who underwent cardiac surgery.

PMID- 18062591
TI  - [The Dutch version of the Radner Reading Chart for assessing vision function].
AB  - A chart for measuring visual acuity is a better functional test than the routine
      distance visual acuity testing with single optotypes. The characteristics of a
      good reading chart are: logarithmically diminishing print size, simultaneous
      measurement of reading acuity and reading speed, and the calculation of one score
      for reading acuity corrected for the number of reading errors. The original
      German-language Radner Reading Chart meets all these requirements, and above all
      emphasizes the principle of 'sentence optotypes' i.e. highly standardized
      sentences, because sentence complexity also influences reading performance.
      Sentence optotypes were created in the Dutch language and tested according to
      Radner's strict principles. The most equally matched sentence optotypes in terms
      of reading speed and number of reading errors were selected for the introduction
      and printing of the first Dutch version of the Radner Reading Chart. The Dutch
      Radner Reading Chart is precise and practical and therefore useful for research
      and daily practice.

PMID- 18062592
TI  - [Recognition of children with sickle cell disease in The Netherlands].
AB  - Timely recognition of clinical signs and symptoms of sickle cell disease remains
      of great importance because the neonatal PKU screening program in The Netherlands
      that was introduced in January 1st 2007 will not reach all children with this
      disease. Of children that have been diagnosed in the Emma Children's Hospital
      AMC, Amsterdam, 20% would not have been reached by this new program: immigrant's
      children born abroad and adopted children. It goes without saying that also in
      children that have been born in the Netherlands before January 1st 2007 the
      diagnosis sickle cell disease should be considered in cases of disease-specific
      clinical symptoms. The initial clinical manifestation of sickle cell disease in
      children born in the Netherlands is potentially life-threatening in 8% (7/88),
      e.g. a pneumococcal infection or an acute splenic sequestration. Painful crisis,
      paleness and jaundice are the most common presenting symptoms. The median age at
      diagnosis of the group of Amsterdam children was 25 months. In view of the
      potential health benefit it is advised to test children from populations at risk,
      that are under the medical attention of a hospital for any reason, for the
      presence of sickle cell disease. This applies especially to children with a
      pneumococcal infection.

PMID- 18062593
TI  - [Diagnostic image (349). A woman with flushes].
AB  - A 57-year-old woman suffered from frequent flushes due to an ovarian carcinoid
      tumour.

PMID- 18062594
TI  - [New drugs; varenicline].
AB  - Nicotine acts in the brain by releasing dopamine in the mesolimbic pathway which
      results in a reward effect and in dependence when used chronically. The effect of
      nicotine is mediated via nicotinergic acetylcholine receptors of the alpha4beta2
      subtype ofwhich varenicline is a partial agonist. Varenicline can be used for
      quitting smoking because of two mechanisms: it acts as a partial agonist and thus
      reduces the symptoms of craving when quitting smoking, and it has antagonistic
      actions by binding the receptor instead of nicotine and therefore decreases the
      reward effect of nicotine. The most important side effects of varenicline are
      nausea, vomiting and headache. After one year, 22% of the treated group continued
      to abstain from smoking.

PMID- 18062595
TI  - [Fewer lung complications following inspiratory muscle training in patients
      undergoing coronary bypass surgery: a randomized trial].
AB  - OBJECTIVE: The aim of this study was to evaluate the prophylactic efficacy of
      preoperative physiotherapy, including inspiratory muscle training (IMT), on the
      incidence of postoperative pulmonary complications (PPCs) in high-risk patients
      scheduled for elective coronary artery bypass grafting (CABG). DESIGN: Randomized
      controlled clinical trial (www.controlled-trials. com/isrctn17691887). METHOD: Of
      655 patients referred to a university medical centre in The Netherlands for
      elective CABG, 299 met the criteria for being at high risk of developing PPCs. A
      total of 279 were enrolled and monitored up to discharge from hospital. Patients
      were randomly assigned to receive either preoperative IMT (n=140) or usual care
      (n=139). Both groups received the same postoperative treatment. RESULTS: Both
      groups were comparable at baseline. Before CABG, 2 control group patients and 1
      IMT group patient died. After CABG surgery, PPCs were present in 25 (18%) of 139
      patients in the IMT group and 48 (35%) of 137 patients in the control group (OR:
      0.52; 95% CI: 0.30-0.92). Pneumonia occurred in 9 (6.5%) of 139 patients in the
      IMT group and in 22 (16.1%) of 137 patients in the usual care group (OR: 0.40;
      95% CI: 0.19-0.84). Mean duration of postoperative hospitalization was 7 (range 5
      41) days in the IMT group versus 8 (range 6-70) days in the usual care group
      (Mann-Whitney test; Z: -2.42; p = 0.015). CONCLUSION: Preoperative physiotherapy,
      including IMT, statistically significantly reduced the incidence ofPPCs and the
      duration ofpostoperative hospitalization in patients at high risk of developing a
      pulmonary complication on undergoing CABG.

PMID- 18062596
TI  - [Early surgery or a wait-and-see policy in lumbosacral radicular syndrome: a
      randomized study].
AB  - OBJECTIVE: To compare early surgery with expectative policy and later surgery if
      necessary in patients with sciatica that did not resolve within 6 weeks. DESIGN:
      Randomized multicentre clinical trial (ISRCTN 26872154). METHODS: Patients who
      had had severe sciatica for 6 to 12 weeks were randomized to early surgery or to
      prolonged conservative treatment with later surgery if necessary. The primary
      outcomes were the Roland Disability Questionnaire score, the visual-analogue
      scale for leg pain score, and the patient's report of their perceived recovery
      over the first year after randomization. Repeated measures analysis according to
      the intention-to-treat principle was used to analyse the outcome curves for both
      groups. RESULTS: A total of 283 patients were included and randomized. Of 141
      patients assigned to undergo early surgery, 125 (89%) underwent microdiscectomy
      after a mean of 2.2 weeks. Of 142 patients assigned to conservative treatment, 55
      (39%) still had to undergo surgical treatment after a mean of 18.7 weeks. There
      was no significant overall difference in disability scores during the first year
      (p = 0.13). Leg pain lessened more quickly in patients assigned to early surgery
      (p < 0.001). Patients assigned to early surgery also reported a faster rate of
      perceived recovery (hazard ratio (HR): 1.97; 95% CI: 1.72-2.22; p < 0.001). In
      both groups, however, the probability of perceived recovery after 1 year of
      follow-up was 95%. CONCLUSIONS: The 1-year outcomes were similar for patients
      assigned to early surgery and those assigned to extended conservative treatment
      with later surgery if necessary but the rates of reduction of leg pain and of
      perceived recovery were faster in those assigned to early surgery.

PMID- 18062597
TI  - [Arthralgia and urticaria as immune-complex mediated complications after
      meningitis with meningococci group B].
AB  - A 4-year-old boy was treated for an infection with a meningococcus type B. After
      a few days of recovery, he felt ill again on day 6. The patient had urticaria and
      arthralgia without arthritis. The infection parameters did not normalize or
      increase in severity. No abnormalities other than a lowered CH50 value were found
      in the extensive diagnostic tests performed. The diagnosis of immune-complex
      mediated complications following a meningococcal infection was made. The patient
      was sent home where he continued pain relief and physiotherapy treatment. After 2
      months at outpatient follow-up, he showed complete recovery and the CH50 value
      had returned to normal. Other immune-complex mediated complications of
      meningococcal infection are arthritis, episcleritis, pericarditis, myocarditis
      and pleuritis. These occur in 6-15% of the patients with a meningococcal
      infection. Early recognition prevents unnecessary extensive and costly diagnostic
      testing as well as a longer than necessary hospital stay.

PMID- 18062598
TI  - [Invasive pneumococcal infection in 5 newborns, 1996-2004].
AB  - At the Maxima Medisch Centrum in Veldhoven, The Netherlands, neonatal sepsis
      caused by invasive Streptococcus pneumoniae infection was diagnosed in 5 neonates
      between 1996 and 2004. This infection is relatively rare and its clinical
      features are variable, but often particularly severe and fulminant as was the
      case in 2 of the 5 children, one of whom died and the other was left with serious
      psychomotor retardation. The other 3 recovered fully. The child who died and one
      of the children who recovered are described in some detail. They were both
      prematurely born neonates, a girl and a boy, who presented almost immediately
      after birth with an early-onset sepsis caused by S. pneumoniae. In both cases
      neonatal cultures as well as maternal vaginal swabs were positive for S.
      pneumoniae growth. 2 different patients had other risk factors for peripartal
      infection. Neonatal pneumococcal infections are most likely transmitted trough
      the maternal vaginal tract. Maternal vaginal colonization is rare (0.11%), but
      associated with a high risk of transmission to the newborn. Asymptomatic neonatal
      colonization was not observed. In light of the likelihood of a high rate of
      transmission and subsequent infection, peripartal prophylactic antibiotic
      treatment is advised for all mothers with proven vaginal S. pneumoniae
      colonization. If this is not given or is not effective, then in contrast with the
      policy on patients with group B streptococcal colonization, prophylactic
      antibiotic treatment is advocated for all neonates born to colonized mothers.
      Amoxicillin is the preferred treatment. In areas of increasing macrolide
      resistance, erythromycin should only be advised in cases of penicillin allergy.

PMID- 18062599
TI  - [Anaphylactic reactions to chlorhexidine during urinary catheterisation].
AB  - Three men of 65, 41 and 54 years old respectively, developed an anaphylactic
      reaction during a medical procedure. Two were under general anaesthesia and the
      third was undergoing urinary catheterisation. After allergy tests chlorhexidine,
      an ingredient in the gel which was used during the urinary catheterisation
      procedure, was found to be the causative agent in all three men. Following
      treatment the clinical course was good. Chlorhexidine is a widely used antiseptic
      and disinfectant. Despite multiple publications on anaphylactic reactions mostly
      during surgery under general anaesthesia or urological procedures, chlorhexidine
      is often initially overlooked as a cause of anaphylaxis. All three men had had
      previous reactions to chlorhexidine, however, not enough attention was paid to
      this fact, or it was not thought of.

PMID- 18062600
TI  - [Gerard Abraham van Rijnberk, editor-in-chief of the Dutch Journal of Medicine
      1913-1946].

PMID- 18062601
TI  - [Antibiotic prophylaxis indicated in dental procedures in patients with a joint
      prosthesis].

PMID- 18062602
TI  - [The work of the Nuffield Center for International Health and Development].

PMID- 18062603
TI  - Progress towards health reform in Tajikistan.
AB  - PURPOSE: The purpose of this paper is to provide an up-to-date overview of
      Tajikistan's health system, focusing on the main factors affecting health systems
      development. The wider contextual environment is to be explored, focusing on
      political, social and economic issues. Different elements of the health system
      including health policy, governance, service delivery, human resources and health
      financing are reviewed in the light of their development over the past decade.
      DESIGN/METHODOLOGY/APPROACH: The paper shows that the Republic of Tajikistan is
      in transition. Formerly one of the most neglected republics within the USSR, the
      country became independent in 1990 and faced the civil conflict shortly
      thereafter. In the last few years there have been major public sector reforms
      with health reforms formally launched in the late 1990s. Little information about
      current Tajikistan is widely available. FINDINGS: The paper finds that the
      progress of health reforms in Tajikistan has been relatively slow compared with
      neighbouring Kazakhstan and Kyrgyzstan. This is largely due to the effects of
      civil war in the mid-1990s and significant out-migration of qualified experts,
      but it can also be attributed to an inability of central government to adequately
      adapt to the requirements of transition. ORIGINALITY/VALUE: The paper shows that
      many problems are still to be overcome by the health system, ranging from
      operational issues related to service delivery to strategic issues such as
      formulating an explicit privatisation policy, reducing fragmentation of, and
      aligning, external aid. However, some recent developments, such as adoption of a
      country health reform conception, a health financing strategy, and willingness of
      central government to improve coordination, suggest that improvements are
      possible.

PMID- 18062604
TI  - Don't forget the bigger picture: the impact of societal issues on a community
      based TB programme, Swaziland.
AB  - PURPOSE: The purpose of this paper is to explore the wider societal issues that
      can impact on the success of a TB programme. DESIGN/METHODOLOGY/APPROACH: The
      paper is a qualitative study of the experiences of people involved in a community
      based DOTS programme in Lubombo, Swaziland, involving patients, DOT treatment
      supporters, clinic nurses and other key informants. FINDINGS: The paper finds
      that study participants spontaneously raised two main societal issues, which had
      major impact on the success of the TB programme: health beliefs and poverty. It
      is seen that health beliefs can have a major impact on treatment-seeking
      behaviour and outcomes of TB treatment. Problems related to poverty were of two
      main types: insufficient funds to attend for review, and lack of food whilst on
      TB treatment. ORIGINALITY/VALUE: This paper discusses why these issues, although
      strictly outside the remit of the health services, are important factors to
      consider when implementing TB programmes. It suggests further research that may
      help break the link between TB and poverty (particularly relating to food
      insecurity) and recommends considering local health beliefs when dealing with
      individuals and the community. Neither the impact of health beliefs nor the
      impact of poverty are new ideas, yet these issues tend to be forgotten by
      quantitative researchers who perhaps understandably focus on issues that may be
      perceived as being easier to measure. This paper serves to remind one of their
      importance and to illustrate the value of qualitative research in highlighting
      them and ensuring that issues that are important to participants are not
      neglected.

PMID- 18062605
TI  - In-country capacity development of a training institute: an Iranian experience.
AB  - PURPOSE: The purpose of this paper is to review the Government initiative for
      developing the in-country capacity of the National Public Health Management
      Centre (NPMC) in Tabriz. The UNDP definition of capacity has been used as a
      framework for assessment with the primary focus of the current assessment being
      on the training component. DESIGN/METHODOLOGY/APPROACH: The pape shows that Iran,
      which is a lower-middle income country, has a network of training institutions
      for both pre-service and continuing education of its human resources in health.
      This collaborative initiative between NPMC, Nuffield Centre for International
      Health and Development (NCIHD) and World Health Organization (WHO), attempted to
      create conditions for designing, organising and conducting a training programme
      in health planning and management for mid-level health managers in Iran.
      FINDINGS: The paper finds that the experience of capacity development through
      training, described here, is in contrast with usual practice, where candidates
      are sent abroad for training. Overall, the process for developing in-country
      capacity of a local institute by a foreign institute was well thought out.
      However, there are some lessons to be learned from the process.
      ORIGINALITY/VALUE: The paper shows that capacity has been built in NPMC for
      organising in-country short course on health planning and management for health
      sector reform. The paper concludes by arguing that, in order to sustain these
      training programmes over a long period of time, in addition to including training
      in its mandate, NPMC should: consider networking with allied institutions in the
      country and beyond for sharing knowledge; and make twinning arrangements with a
      foreign institute for continuously upgrading the knowledge and skills of its
      trainers.

PMID- 18062606
TI  - Health system decentralisation in Nepal: identifying the issues.
AB  - PURPOSE: The purpose of this paper is to describe and discuss policy analysis in
      Nepal and review the wide range of choices feasible in decentralisation decision
      making. DESIGN/METHODOLOGY/APPROACH: In this paper an iterative qualitative
      method was developed and used in the research, which consisted of focus group
      interviews, key informant interviews, document analysis, including descriptive
      statistics, and analysis of the policy context. Participants in the research
      reflected the urban/rural mix of districts and the geography of Nepal. Analysis
      combined transcribed interviews with findings from document searches and analysis
      of the policy context. Coding was pre-determined during the training workshop and
      further codes were generated during and after the fieldwork. FINDINGS: The paper
      finds that Nepal is in the process of decentralising public services from the
      central level to the local level, particularly to local bodies: District
      Development Committees (DDCs), Village Development Committees (VDCs) and
      Municipalities. Key contextual factors referred to are the overall structure of
      decentralisation, the social context of poverty and the political instability
      leading to a fluid political situation characterised by political tension, armed
      conflict, controversies and agreements while carrying out the research. The key
      issues identified and discussed in the paper are the policy process leading to
      decentralisation, the organisational structure and tension in the proposed
      system, the systems of resource generation, allocation, planning and management
      and lastly the forms of accountability, participation, public-private relations
      and collaborative strategies. ORIGINALITY/VALUE: The paper discusses the
      challenges faced in conducting such a policy analysis, the broad ranging and
      unremitting nature of the decentralisation process, and the contextual setting of
      the process of change.

PMID- 18062607
TI  - Estimated numbers of new TB cases in Patan, a city in Nepal.
AB  - PURPOSE: The purpose of the paper is to show that, despite comprehensive coverage
      of services for TB provided by a public-private partnership for TB control in
      Patan, a city in Nepal, case finding is low, compared with the target based on an
      Annual Risk of Tuberculosis Infection (ARTI) of 4 per cent. Doubts have been
      raised as to the appropriateness of the target. The objective of the study was to
      estimate the number of new TB cases occurring in Patan, to assess whether the
      target was appropriate. DESIGN/METHODOLOGY/APPROACH: In the paper doorstep
      interviews were conducted with all households in the study area, followed by in
      depth interviews of households with possible or probable TB cases. The survey
      findings were validated against the patient registers of the five DOTS centres in
      Patan. FINDINGS: The paper finds that, among the study population of 36,918, the
      household survey identified 17 smear-positive TB cases (none privately-treated)
      and 24 smear-negative/extra-pulmonary cases (including four privately-treated
      cases). Validation against the DOTS patient registers indicated that the survey
      was 54 per cent complete. After adjusting for incompleteness, the number of smear
      positive cases in the study area was estimated as 31, equivalent to an incidence
      of 85 smear positives per 100,000 population and an ARTI of 1.7 per cent.
      ORIGINALITY/VALUE: The paper shows that using the ARTI may lead to misleadingly
      high targets for urban TB control. Unrealistically high targets may cause TB
      workers to become demoralised, and useful strategies to be abandoned. Therefore,
      further work is needed to identify better ways of setting targets.

PMID- 18062608
TI  - The contribution of volunteers to a successful community-orientated tuberculosis
      treatment centre in an urban setting in Nepal: a qualitative assessment of
      volunteers' roles and motivations.
AB  - PURPOSE: The purpose of the paper is to show that community involvement is a
      successful way of overcoming certain barriers to the successful management of the
      current tuberculosis epidemic, namely delayed presentation and non-completion of
      treatment. Volunteers are an important resource for engaging with the community.
      This research, conducted in an urban TB treatment centre in Nepal, seeks to
      investigate the motivations of TB volunteers, and how these motivations can be
      increased to involve volunteers, and the community, in fulfilling their maximum
      potential in delivering successful TB treatment programmes.
      DESIGN/METHODOLOGY/APPROACH: Semi-structured interviews were carried out with 26
      TB volunteers, followed by volunteer discussion groups. Topics covered included:
      detailed accounts of the volunteers' many and varied roles; motivations - how
      they initially became involved and why they continue to be involved; incentives
      for volunteering; problems they have encountered; family and friends' attitudes
      to their volunteering, and the future of TB volunteering. FINDINGS: The findings
      show that the TB volunteers are involved in many important roles. Volunteers
      initially became involved, having been asked or informed about the programme by
      area committee members, staff or friends. Most were also involved in other
      voluntary work. ORIGINALITY/VALUE: This paper gives recommendations for volunteer
      programmes in developing countries including: sustained communication and contact
      between volunteers and the organisation; volunteer programmes based in a centre
      with an established community focus; flexibility of time commitment; regular
      recruitment drives for volunteers from different generations and status levels;
      and the use of training as a possible incentive for volunteering.

PMID- 18062609
TI  - International health in medical education: students' experiences and views.
AB  - PURPOSE: The purpose of this paper is to describe the experiences and views of
      the first group of medical students to complete the intercalated International
      Health BSc in Leeds. DESIGN/METHODOLOGY/APPROACH: The paper draws on experiences
      of international health and draws parallels with those of other international
      health students. The paper also discusses how studying international health may
      benefit future doctors and considers how medical education can take a more
      international approach. FINDINGS: The paper finds that international health
      education can help future doctors acquire knowledge and skills in refugees'
      health, patients' cultural differences, the multifactoral influences on health,
      policymaking, the interests of various stakeholders, problem-solving skills and
      evidence-based medicine. PRACTICAL IMPLICATIONS: The paper shows that
      international health teaching is both relevant and valuable in medical education.
      The medical profession should give more recognition to its worth.
      ORIGINALITY/VALUE: This is the first paper to reflect on medical students'
      experiences of studying for an intercalated BSc at Leeds. It makes some important
      points about international health education for doctors and medical students
      world-wide.

PMID- 18062610
TI  - Perceptions of the health effects of stoves in Mongolia.
AB  - PURPOSE: The purpose of this paper is to evaluate the views of stove users in
      Ulaanbaatar, Mongolia on how stoves affect their health.
      DESIGN/METHODOLOGY/APPROACH: In this paper focus groups were conducted with
      improved stove users; traditional stove users; and a mix of traditional and
      improved stove users. Individual interviews were also held with various types of
      stove users. A translator moderated all discussions with a questioning route. All
      discussions were fully transcribed and translated. The transcripts were analysed
      by identifying common themes in responses to form an emerging theory. FINDINGS:
      The findings in the paper are that all stove users recognised respiratory
      symptoms caused by stove smoke and other health effects such as warmth, dirt and
      workload, which they perceived to be important. Stove users had a lack of
      knowledge about the diseases caused by the smoke. Public health was a key driver
      for the improved stove project, yet has been neglected in improved stove
      marketing. RESEARCH LIMITATIONS/IMPLICATIONS: The study used in this paper was
      limited by the language barrier. Some of the meanings of participants' responses
      may have been lost in translation. PRACTICAL IMPLICATIONS: This paper has
      highlighted the importance of the health effects of stove smoke to stove users.
      Uptake of the improved stoves has been low. Public health should be included in
      marketing strategies for improved stoves to increase their uptake.
      ORIGINALITY/VALUE: The paper shows that acute respiratory infections are a major
      cause of mortality world-wide. Indoor air pollution from burning biomass fuels in
      household stoves causes a significant proportion of respiratory infections. No
      qualitative research has been published exploring stove users' views on the
      health effects of stoves. This paper provides an insight into stove users'
      perceptions for those interested in people-centred approaches to tackling
      international health issues.

PMID- 18062613
TI  - The lymphatics of the skin filled by a dermal backflow: an observation in a
      scarred cadaver leg.
AB  - There have been few photographic studies done on lymphatics of human skin with
      previous images obtained by indirect dye injection into the dermis. We have
      developed a direct injection technique for investigating the lymphatic system in
      human adult cadavers and used this to investigate superficial lymphatics of the
      legs in a fresh human cadaver. We found an unusual observation in a skin graft
      scarred leg when the radio-opaque mixture injected into a lymph collecting vessel
      in the dorsal foot filled the skin lymphatics in the mid-lateral pretibial
      region. Further radiological investigation revealed that the dermal back flow was
      associated with a blockage of the lymph collecting vessel within the skin graft
      scar. We also found tracer transport through a circuitous pathway from the
      blocked collecting vessel to an adjacent intact collecting vessel. The
      transilluminated image of the skin demonstrated a three dimensional polygon of
      lymph capillaries and precollecting lymphatics in the dermis.

PMID- 18062611
TI  - Mechanotransduction in lymphatic endothelial cells.
AB  - Initial lymphatic vessel endothelial cells are connected to the surrounding
      elastic fibers by fibrillin anchoring filaments that have been hypothesized to
      favor interstitial fluid drainage in edema pulling apart interendothelial
      junctions. We hypothesized a biochemical mechanism involving mechanotransduction.
      This study was designed to verify whether a relation exists between focal
      adhesion molecules and anchoring filaments and whether they may transduce
      extracellular forces to the nucleus. We first performed an immunohistochemical
      study on human skin cryostat sections to evaluate whether fibrillin and alphav
      beta3 integrins, FAK and fibrillin, or alphav-beta3 integrins and FAK co-localize
      in lymphatic endothelium. We observed that integrins and FAK co-localize and that
      fibrillin filament attachment sites to endothelial cells merge with these
      molecules. These data may suggest that fibrillin anchoring filaments are
      connected to endothelial cells through focal adhesions. Mechanotransduction was
      investigated applying static stretching to bovine thoracic duct segments and
      lymphatic endothelial cells cultured on elastic membranes and
      immunohistochemically evaluating the expression of ERK1/2. Under stretching
      conditions, ERK1/2 labels the nucleus. Western blotting on cultured cells
      confirmed the presence of ERK1/2 in stretched cells. Based on our data we
      speculate that anchoring filaments may trigger a focal adhesion-mediated cascade
      of mechanotransduction toward the nucleus for genetic modulation and thus
      contribute to endothelial adaptation to interstitial requirements.

PMID- 18062614
TI  - Contrast demonstration of the diaphragmatic lymphatics into the thorax.

PMID- 18062612
TI  - Immunohistochemical studies in a hydroptic fetus with pulmonary lymphangiectasia
      and trisomy 21.
AB  - This case report presents a hydroptic trisomy 21 fetus affected by lymphatic
      dysplasia with no other malformations. Our studies using CD31, CD34, smooth
      muscle actin, desmin, and D2-40 antibodies immunohistochemistry confirm the
      diagnosis of severe pulmonary lymphangiectasia associated with lymphangiectasia
      ih the mediastinum and small bowel.

PMID- 18062615
TI  - Endermologie (with and without compression bandaging)--a new treatment option for
      secondary arm lymphedema.
AB  - Two treatment protocols are presented using the LPG Endermologie system in
      combination with compression bandaging as a new treatment option for secondary
      arm lymphedema. Both protocols were applied 4 days a week for 4 weeks but
      differed in Trial II in time spent clearing the regions of the trunk adjacent to
      the swollen limb and the addition of a larger treatment head so that a greater
      area could be covered more quickly. The first protocol involved 24 women and the
      second involved 10 women. At the end of the treatment period, both protocols
      demonstrated overall reductions in limb volume (134mls; 18.3% p = 0.000 and
      185mls; 28%, p = 0.002), limb fluid (182mls; 28%, p = 0.000 and 216mls; 33%. p =
      0.014), truncal fluid (342mls; p = 0.002 and 290mls; p = 0.066), improvements in
      fibrotic induration in some lymphatic territories, and significant improvements
      in subject reporting of heaviness, tightness, tissue hardness and limb size.
      Trial II demonstrated additional benefits in terms of reduction in whole arm
      volume at 24 hours, improved fluid and arm volume reductions, and a significant
      improvement in subject reported arm range of movement. The additional time spent
      clearing the regions adjacent to the swollen limb in the second protocol appears
      to produce an increase in limb volume and limb fluid loss compared to the
      original treatment protocol.

PMID- 18062616
TI  - Manual lymph drainage efficiently reduces postoperative facial swelling and
      discomfort after removal of impacted third molars.
AB  - The removal of wisdom teeth is often associated with severe postoperative edema
      and pain, and operation on the third molar can cause local inflammation that
      impairs lymph transport. The objective of the study was to assess the efficacy of
      manual lymph drainage (MLD) in reducing swelling following bilateral wisdom tooth
      removal. Ten consecutive patients with bilateral impacted wisdom teeth that
      required surgical removal were enrolled in the study. Each patient was
      postoperatively treated with MLD (after Vodder's method) on one side of the neck
      region with the untreated contralateral side as a control. Swelling was evaluated
      using a tape-measure placed in contact with the skin. The six landmarks of
      measurement included tragus-lip junction, tragus-pogonion, mandibular angle
      external corner of eye, mandibular angle-ala nasi, mandibular angle-lip junction,
      and mandibular angle-median point of chin. Subjective assessment of MLD was
      conducted with self-evaluation using a visual analogue bar scale (VAS, range 0
      100 mm). Of the 6 linear measurements, 4 lines (2, 4, 5, 6) showed a significant
      reduction of swelling on the side of MLD compared to the untreated side. Mean
      score of VAS of pretreatment condition was 35.5 +/- 20.60 mm that decreased to 22
      +/- 19.32 mm measured after MLD (p=0.0295). This initial study demonstrates that
      MLD may promote an improvement of lymph circulation and work in an adjunctive
      role for reduction of postoperative swelling and pain following removal of
      impacted third molars.

PMID- 18062617
TI  - Effect of complex decongestive therapy on edema and the quality of life in breast
      cancer patients with unilateral leymphedema.
AB  - There is increasing interest in the health-related quality of life (QOL) of
      patients with chronic lymphedema. The aim of this study was to ascertain whether
      complex decongestive therapy (CDT) for upper limb lymphedema results in long-term
      changes in lymphedema and QOL, and to determine whether the treatment-induced
      change in the percentage excess volume (PCEV) is correlated with any changes in
      QOL. Fifty-three patients who had lymphedema were treated with CDT. PCEV and QOL
      were recorded before and 1 month after CDT, and at a 6-month follow-up visit.
      PCEV was significantly (p<0.05) decreased at 1 month, but significantly (p<0.05)
      increased at 6 months compared to 1 month [but still significantly reduced
      (p<0.05) from baseline]. The QOL scores at 1 and 6 months were significantly
      higher than the score at baseline, indicating an improvement in the QOL.
      Significant changes were evident in the single domains of physical functioning,
      role-physical, mental health, and general health. The change in PCEV was
      associated with a change in physical functioning, vitality, bodily pain, and
      general health at 1 and 6 months (p<0.05). This study suggests that QOL
      significantly improved with upper limb lymphedema during the maintenance phase,
      which was necessarily correlated with the reduction in limb volume.

PMID- 18062618
TI  - A view from above: use of satellite imagery to enhance our understanding of
      potential impacts of climate change on human health in the Arctic.
AB  - OBJECTIVE: Provide an overview and examples of some of the remote sensing
      technologies presently or potentially available, which could be used to address
      environmental health problems in the Arctic. STUDY DESIGN: The vulnerability of
      Arctic populations to health impacts from environmental, weather, and climate
      related factors underscores the need for increased applications of technologies
      such as remote sensing, Geographic Information Systems (GIS), and global
      positioning systems (GPS) for empowering local health officials and decision
      makers to better predict environment-related health problems, decrease
      vulnerabilities, take preventative measures, and improve community response
      actions as well as increase community health literacy. METHODS/RESULTS: These
      increased capabilities for monitoring, risk mapping, information sharing,
      communications, and surveillance of environmental parameters are powerful tools
      for addressing such environmentally-related health problems as thermal stress;
      extreme weather; contaminant transport and deposition into oceans, atmosphere,
      and ice; air and water quality; built environment impacts; ultraviolet radiation
      (UV); and infectious and vector-borne diseases. For example, systems are now in
      place, which can observe ocean parameters, providing information on algal blooms,
      pollutants and pathogens as well as storm assessments and sea level rise.
      CONCLUSION: Space-based systems in place can contribute valuable information
      through monitoring the processes of long-range transport of pollutants to the
      Arctic, where accumulation in animals and plants can occur. It is well-known that
      biomagnification up the food chain and ultimate consumption as traditional foods
      by indigenous peoples have resulted in some of the highest exposures in the world
      to certain contaminants.

PMID- 18062619
TI  - Tanana days.

PMID- 18062620
TI  - Lamenting unwelcome 'gifts' of job. 1976.

PMID- 18062621
TI  - [Complementary nursing methods in sleep disorders: gentle aids instead of
      chemical club].

PMID- 18062622
TI  - [Dispensing comfort in emotionally charged situations: "I told her it is ok to
      cry"].

PMID- 18062623
TI  - [Organ centers in oncology--exemplified by Aalen Ostalb Clinic: more
      responsibility in nursing].

PMID- 18062624
TI  - [Effects of personnel supply on risk of infection in the intensive care unit].

PMID- 18062625
TI  - [Managing nursing errors and legal sequelae: documentation plays a major role].

PMID- 18062626
TI  - [Judgment regarding patient homicides in the Berlin Charite: courage is needed].

PMID- 18062627
TI  - [Results of a study on fatigue in breast cancer patients receiving adjuvant
      chemotherapy: the first four days after treatment are the worst].
AB  - A large number of breast cancer patients receiving adjuvant chemotherapy is
      suffering from fatigue. Until now there has been a lack of knowledge concerning
      the course of fatigue in breast cancer patients between two cycles of adjuvant
      chemotherapy. Therefore a prospective cohort study was conducted including 151
      breast cancer patients from six hospitals in The Netherlands. The object of the
      study was to investigate the course of fatigue between the third and the fourth
      cycles of adjuvant chemotherapy, and to prove whether that course is influenced
      by different chemotherapy schedules. The patients were treated either with a
      doxorubicin containing schedule (21 or 28 days) or with a combination of
      cyclophosphamide, methotrexate, and 5-fluorouracil (CMF, 28 days). To assess
      fatigue patients were asked to write a diary cotaining the Shortened Fatigue
      Questionnaire (SFQ) from the beginning of the third cycle to the start of the
      fourth one. All days after completion of the third chemotherapy treatment were
      analysed. The main hypothesis to be tested was that the maximum fatigue level
      occurs in the first four days after treatment. Results revealed a chaotic pattern
      of fatigue between both cycles of chemotherapy in each of the treatment group.
      Smooth (splines) curves showed an average highest level of fatigue on day 3 post
      treatment. For the regimens with 28-days-intervalls another peak of fatigue was
      registered on day 11. A significant larger number of patients experienced maximum
      fatigue levels before day 5. The course of fatigue in the CMF group was
      significantly different compared with both doxorubicin groups. Women of the CMF
      group experienced lower fatigue peaks than patients of other groups. The results
      confirm the main hypothesis. The first days after treatment with chemotherapy are
      the worst ones for breast cancer patients. The course of fatigue is significantly
      related to the type of chemotherapy. Knowing these effects patients can better
      prepare oneself and their daily living for the time of adjuvant chemotherapy.

PMID- 18062628
TI  - [Cancer pain from the nurses' perspective--findings from Austria].
AB  - The present study addresses the issue of cancer pain from the perspective of
      Austrian nurses. By the means of a standardised questionnaire 332 nurses (79
      percent female, 63 percent with age < 40) were asked about causes and triggers of
      cancer pain, patients' burden of pain, used analgesics and their side effects,
      and the authority by whom they want to be informed about an own malignant
      disease. The respondents mentioned a wide range of causes, triggers and
      multipliers of cancer pain. According to the respondents, most cancer patients
      experience pain that exceeds the degree of pain a person can bear. Many side
      effects of use of analgesics are observed. In case of an own malignant disease
      the majority of the interviewees would like to be informed by a physician. The
      results point out that nursing personnel is aware of the patients' burden of
      pain, but at the same time they show the need for improvement at clinical pain
      management and in the area of vocational training and advanced nursing education.

PMID- 18062629
TI  - [Screening for colon cancer reduces mortality].

PMID- 18062630
TI  - [Foreign country placement to the West African coast: "We would not want to miss
      those months"].

PMID- 18062631
TI  - [Step by step for nursing competence--7: Position change in bed: promoting
      patient mobility].

PMID- 18062632
TI  - [Recognizing and understanding disorders: vertigo as the leading marker].

PMID- 18062633
TI  - [On the right way towards fair health care in an unfair world?].

PMID- 18062634
TI  - [New Strama-work in Ostergotland. The LIRA-concept gives best results].

PMID- 18062635
TI  - [Children with urinary tract infections--new guidelines for investigation and
      therapy. Focus on children with risk factors as recommended by NICE].

PMID- 18062637
TI  - [No unified guidelines concerning gestational diabetes in Sweden. Noticeable
      differences between screening, diagnostics and management in maternal health
      services].

PMID- 18062636
TI  - [National quality registry for in-hospital cardiac arrest now started].

PMID- 18062638
TI  - [TSH-secreting pituitary adenomas can be easily missed. A rare condition with
      differential diagnostic difficulties].

PMID- 18062639
TI  - [Obliterative bronchiolitis after stem cell transplantation. Inert gas washout
      makes early diagnosis of this serious complication possible].

PMID- 18062640
TI  - [TNF-alpha inhibitors and demyelinating disease].

PMID- 18062641
TI  - [Health as a human right. Sharp criticism of Sweden by the UN calls for
      rethinking].

PMID- 18062642
TI  - [Human rights in the medical education curriculum!].

PMID- 18062643
TI  - [Trans-cultural psychiatry more and more important with increasing migration].

PMID- 18062644
TI  - [The DAMP diagnosis in needed].

PMID- 18062645
TI  - [Easy to create work situations which increase the risk of burnout].

PMID- 18062646
TI  - [The most prominent Swedish water-color painter--a "drab" survivor].

PMID- 18062647
TI  - Multiplex-PCR assay for identification of Klebsiella pneumoniae isolates carrying
      the cps loci for K1 and K2 capsule biosynthesis.
AB  - Multiplex-PCR assay for identification of Klebsiella pneumoniae isolates carrying
      gene clusters for biosynthesis of capsular polysaccharide (CPS) types K1 and K2
      was developed. Genes wzc and orf10 of the cps cluster were applied as K1 and K2
      specific markers respectively. The assay specificity was confirmed using 147
      isolates of Klebsiella spp. including 77 K-antigen reference strains. The
      multiplex-PCR assay was found simple and cost-effective tool for identification
      of K. pneumoniae clinical isolates of K1 and K2 geno-serotypes.

PMID- 18062648
TI  - FAME profiles in Pseudomonas vesicularis during catechol and phenol degradation
      in the presence of glucose as an additional carbon source.
AB  - The aim of this study was to evaluate the impact of catechol and phenol added to
      culture media separately and with glucose as an additional, easily-degradable
      carbon source on fatty acid methyl ester (FAME) composition in Pseudomonas
      vesicularis. Simultaneously, the degradation rates of aromatic substrates used
      were investigated in single and binary substrate systems. Both catechol and
      phenol treatments caused changes in the distribution of tested groups of fatty
      acids. The most noticeable changes included an increase in degree of fatty acid
      saturation, the appearance of branched and disappearance of hydroxy fatty acids
      as compared to the control sample with glucose. Under catechol or phenol
      treatment sat/unsat ratio showed the values of 8.63 and 11.38, respectively,
      whereas in control cells it reached the value of 2.66. The high level of
      saturation comes from the high content of cyclopropane fatty acids in bacteria
      under exposure to aromatic substrates, regardless of the presence of glucose. In
      these treatments their content was more than 3-fold higher compared to the
      control. It has been demonstrated that glucose supplementation of culture media
      containing single aromatic substrate extended the degradation rates of catechol
      and phenol by P. vesicularis, caused an increase in number of cells but did not
      significantly change the fatty acid profiles in comparison with bacteria growing
      on catechol and phenol added to the media individually.

PMID- 18062649
TI  - Reliability of the Etest in light of the correlation between an antibiotic's
      critical concentration (Cc) and MIC values.
AB  - The study relates to the theory of diffusion methods for antibiotic sensitivity
      testing. The aim of the study was to show the relationship between the antibiotic
      critical concentration (Cc) and its minimum inhibitory concentration (MIC). The
      results contribute to the explanation of the Etest's reliability and support the
      scientific basis for MIC determination using agar diffusion methods.
      Susceptibility among 90 clinical isolates of 12 common aerobic bacterial species
      to gentamicin, erythromycin, or oxacillin was assessed using the multidisc method
      (for Cc), by the agar dilution method (for MIC) and by the Etest. The results of
      all three methods were statistically compared and found to be closely related.
      The regression equation for Cc values and MIC was log2(MIC) = 0.99 x log2(Cc)
      0.13; r = 0.99; p < 0.05; the regression equation for Cc values and Etest-MIC
      (Et) was log2(Et) = 0.86 x log2 (Cc)+0.34; r = 0.96; p < 0.05; the regression
      equation for Etest-MIC values and MIC was log2(MIC) = 1.12 x log2(Et)-0.50; r =
      0.96; p < 0.05.

PMID- 18062650
TI  - Antibiotic susceptibility and molecular characterisation of Proteus mirabilis
      isolates in hospitals from the West Pomeranian area of Poland.
AB  - Proteus mirabilis isolates (n = 177), collected between 1996 and 2000 in four
      hospitals in the West Pomeranian area of Poland, were characterized by
      antibiotype and pulsed-field gel electrophoresis (PFGE). The selected isolates
      were collected from different wards (intensive care unit, surgery, internal
      medicine, and urology). The strains were cultured from various specimen types,
      mostly from urine, wound samples, bronchial exudates and sputa. The
      identification was done by biochemical test ID 32E ATB (bioMerieux). Analysis of
      PFGE patterns was based on comparison of the banding patterns obtained by PFGE of
      chromosomal DNA digested with SfiI enzyme. Among all P. mirabilis isolates tested
      three major genotypes A (A1-A7), B (B1-B4), C (C1-C5) and 71 unique patterns were
      identified. The same genotypes were obtained from different patients, treated in
      different wards and hospitals during a 5-year period. The strains which belonged
      to the genotypes A and B were multiresistant and most of them produced ESBL;
      genotype C was more sensitive to antibiotics.

PMID- 18062651
TI  - Prevalence of antibiotic resistance profile in relation to phylogenetic
      background among commensal Escherichia coli derived from various mammals.
AB  - The paper describes the prevalence of resistant strains within the genetic
      structure of E. coli (phylogenetic group A, B1, B2 and D). A total of 200
      commensal E. coli strains have been derived from 10 species of healthy animals
      residing on ZOO Safari Park area, in Swierkocin, Poland. The phylogenetic
      structure of E. coli has been analysed with the use of a PCR-based method. The
      strains were tested in terms of their susceptibility to eight classes of
      antibiotics: aminoglycosides, penicillins, cephalosporins, tetracyclines,
      nitrofurans, sulphonamides, phinicols, and quinolones. The genetic structure of
      E. coli revealed a not uniform distribution of strains among the four
      phylogenetic groups with significantly numerous representation of groups A and
      B1. Resistant E. coli were found within each of the phylogenetic groups. Strains
      resistant to one class of antibiotics occurred significantly more frequently in
      phylogenetic groups B2 and D (potential pathogens), whereas strains resistant to
      more than one class of antibiotics belonged to phylogenetic groups A and B1
      (typical commensals) in a prevailing number of cases.

PMID- 18062652
TI  - Human neutrophil peptides in vaginitis/cervicitis of different etiology.
AB  - Development of female genito-urinary infections depends on many factors, such as
      immune system activity, virulence of microorganism and production of factors
      inhibiting the growth of microorganisms. Taking into account the possibility of
      relapses or severe complications, it is very important to appropriately diagnose
      and treat infections. Because of recently observed increase of microbial
      resistance to antibiotics, researchers are looking for alternatives. In our study
      we evaluated and compared the concentration of human neutrophil peptides (HNP 1
      3) in cervico-vaginal lavages (CVL), obtained from women with
      vaginitis/cervicitis. Swabs from the posterior vaginal fornix and from the
      endocervical canal as well as CVL samples were obtained from 32 patients with
      vaginitis/cervicitis and 29 healthy women (control group). Supernatants of CVL
      were used for determination of concentration of HNP by ELISA. The difference
      between concentrations of HNP 1-3 in studied and control groups was statistically
      significant (p = 0.018). The maximal concentration was determined in patients
      with mixed infections (28.41 ng/ml), and Group B Streptococci, GBS, (28.06
      ng/ml), the minimal concentrations in cases of C. trachomatis (mean
      concentrations did not differ from those in the control group: 16.93 ng/ml and
      16.39 ng/ml, respectively). Maximal correlation was determined for control
      studied group with isolation of GBS (r = 0.79), and very high negative
      correlation for group of GBS - C. trachomatis (r = -0.98).

PMID- 18062653
TI  - Biological activity of phenylpropionic acid isolated from a terrestrial
      Streptomycetes.
AB  - The strain ANU 6277 was isolated from laterite soil and identified as
      Streptomyces sp. closely related to Streptomyces albidoflavus cluster by 16S rRNA
      analysis. The cultural, morphological and physiological characters of the strain
      were recorded. The strain exhibited resistance to chloramphenicol, penicillin and
      streptomycin. It had the ability to produce enzymes such as amylase and
      chitinase. A bioactive compound was isolated from the strain at stationary phase
      of culture and identified as 3-phenylpropionic acid (3-PPA) by FT-IR, EI-MS, 1H
      NMR and 13C NMR spectral studies. It exhibited antimicrobial activity against
      different bacteria like Bacillus cereus, B. subtilis, Escherichia coli,
      Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, P. flourescens,
      Staphylococcus aureus and some fungi including Aspergillus flavus, A. niger,
      Candida albicans, Fusarium oxysporum, F. udum and Penicillium citrinum. The
      antifungal activity of 3-PPA of the strain was evaluated in in vivo and in vitro
      conditions against Fusarium udum causing wilt disease in pigeon pea. The compound
      3-PPA is an effective antifungal agent when compared to tricyclozole (fungicide)
      to control wilt caused by F. udum, but it exhibited less antifungal activity than
      carbendazim.

PMID- 18062654
TI  - Ultra-structural studies on root nodules of Samanea saman (Jacq.) Merr.
      (Leguminosae).
AB  - Ultra-structural studies were conducted on root nodules of Samanea saman (Jacq.)
      Merr. collected from trees growing under natural conditions. Nodules were
      distributed singly as well as in clusters on the main and lateral roots. Mature
      nodules were elongated, branched and coralloid. Root hair curling was found but
      infection threads could not be observed. Rhizobia entered through the epidermis
      and moved intercellularly through the cortical region. Mature nodules of S. saman
      could be differentiated into meristem, cortex, vascular tissue and bacteroid
      tissue. The latter showed both infected and non-infected cells mixed together.
      Vascular bundles were inversely collateral and distributed around the bacteroid
      tissue. The bacteroids were enclosed in peribacteroid membrane in groups and
      showed prominent granules of polyhydroxybutyrate in their cytoplasm. Mycorrhizal
      hyphae were also observed along with rhizobia in the bacteroid tissue. S. saman
      with dual rhizobial and mycorrhizal infection is a potential tree for plantation
      in arid soils of Pakistan.

PMID- 18062655
TI  - Growth and antioxidant activity of Desulfotomaculum acetoxidans DSM 771
      cultivated in acetate or lactate containing media.
AB  - Three independent 28 or 32-day stationary cultures of Desulfotomaculum
      acetoxidans DSM 771 strain were carried out under anoxic conditions in acetate or
      lactate-containing media. The acids were the sole carbon and energy sources in
      these media. During cultivation the turbidity (for calculation of cell division
      index) and hydrogen sulfide contents were determined in culture broth and reduced
      glutathione and protein concentrations were assayed in culture broth supernatant.
      In these three successive cultures, the bacterium initially grew much faster on
      lactate than on acetate. However, after two weeks of culture this difference
      disappeared and in fact the growth rate was higher on acetate than on lactate.
      The level of H2S formed (product of the dissimilatory pathway of sulfate
      reduction) demonstrated that this pathway was more effective when lactate was a
      carbon source and the average H2S concentration was from over 3-fold to about 9
      fold greater in lactate than in acetate cultures. Also GSH (glutathione, product
      of the assimilatory sulfate reduction pathway) average level was about 2-fold
      higher in lactate-grown cultures. The high negative values of the correlation
      coefficients between GSH and O2 levels, especially during the first 4 days of
      cultivation, indicate that GSH is a very important antioxidizing extracellular
      agent of D. acetoxidans. The rapid increase in GSH level, preceding the release
      of H2S, indicates the metabolic priority of the assimilation pathway of sulfate
      reduction. For both carbon sources the highest coefficient of correlation was
      found between protein and H2S levels. These results suggest that hydrogen sulfide
      is bound by proteins (which contain cysteinyl residues) secreted by D.
      acetoxidans cells. Indicated way of H2S bounding could result in its
      accumulation. This coefficient of correlation increased gradually in the
      successive cultures. The ratio of H2S concentration to protein concentration
      increased gradually in the successive cultures, too.

PMID- 18062656
TI  - Bioremediation of aflatoxins by some reference fungal strains.
AB  - Aspergillus parasiticus RCMB 002001 (2) producing four types of aflatoxins B1,
      B2, G1, and G2 was used in this study as an aflatoxin-producer. Penicillium
      griseofulvum, P. urticae, Paecilomyces lilacinus, Trichoderma viride, Candida
      utilis, Saccharomyces cerevisiae as well as a non-toxigenic strain of Aspergillus
      flavus were found to be able to exhibit growth on aflatoxin B1-containing medium
      up to a concentration of 500 ppb. It was also found that several fungal strains
      exhibited the growth in co-culture with A. parasiticus, natural aflatoxins
      producer, and were able to decreased the total aflatoxin concentration, resulting
      in the highest inhibition percentage of 67.2% by T viride, followed by P.
      lilacinus, P. griseofulvum, S. cerevisiae, C. utilis, P. urticae, Rhizopus
      nigricans and Mucor rouxii with total aflatoxin inhibition percentage of 53.9,
      52.4, 52, 51.7, 44, 38.2 and 35.4%, respectively. The separation of
      bioremediation products using GC/MS revealed that the toxins were degraded into
      furan moieties.

PMID- 18062657
TI  - Lipopolythiourea transfecting agents: lysine thiourea derivatives.
AB  - Synthetic vectors represent an alternative to recombinant viruses for gene
      transfer. We have recently explored the transfection potential of a class of
      noncationic lipids bearing thiourea moieties as DNA-associating headgroups. The
      encouraging results obtained with lipopolythioureas derived from serinol prompted
      us to further investigate this family of vectors. In the present study, we
      considered the transfection properties of a series of derivatives based on a
      different thiourea polar headgroup bearing a lysine scaffold. The synthesis of
      these compounds could be readily achieved in three steps with good yields. We
      found that these lipopolythioureas (LPT) might be considered as alternative
      systems for gene transfection since their activity reached the same magnitude
      range as that of cationic vectors in the presence of serum. LPT with 14-carbon
      length chains appeared to be more efficient as a transfecting agent than the ones
      with shorter chains. Toxicity studies proved that the hydration film method led
      to particles well tolerated both by the cells in vitro and by the mice in vivo.
      The ability to induce gene expression in vivo was demonstrated by intratumoral
      injection. Finally, biodistribution studies showed that the quantity recovered in
      blood circulation, 2 h after systemic injection, was improved as compared to that
      in cationic lipids.

PMID- 18062658
TI  - Well-defined nanoassemblies using gold nanoparticles bearing specific number of
      DNA strands.
AB  - The accurate assembly of nanoparticles into specially designed structures is
      important for the application of nanoparticle-based materials. Here we report the
      fabrication of well-defined nanoparticle assemblies via the grouping of gold
      nanoparticles bearing a specific number of short DNA per particle. Furthermore,
      we explored various conditions that affect the grouping. Our results show that
      direct linkage of two nanoparticle-bound DNA without the use of linker DNA yields
      80% grouping, which is the highest of all conditions tested. Longer hybridization
      times and buffer conditions with higher ionic strength also increase grouping
      formation. These results provide key knowledge that controls the hybridization of
      nanoparticle-bound DNA for achieving well-defined nanoassemblies with high yield.

PMID- 18062659
TI  - Application of an environmentally sensitive fluorophore for rapid analysis of the
      binding and internalization efficiency of gene carriers.
AB  - Nonviral gene carriers must associate with and become internalized by cells in
      order to mediate efficient transfection. Methods to quantitatively measure and
      distinguish between cell association and internalization of delivery vectors are
      necessary to characterize the trafficking of vector formulations. Here, we
      demonstrate the utility of nitro-2,1,3-benzoxadiazol-4-yl (NBD)-labeled
      oligonucleotides for discrimination between bound and internalized gene carriers
      associated with cells. Dithionite quenches the fluorescence of extracellular NBD
      labeled material, but is unable to penetrate the cell membrane and quench
      internalized material. We have verified that dithionite-mediated quenching of
      extracellular materials occurs in both polymer- and lipid-based gene delivery
      systems incorporating NBD-labeled oligonucleotides. By exploiting this property,
      the efficiencies of cellular binding and internalization of lipid- and polymer
      based vectors were studied and correlated to their transfection efficiencies.
      Additionally, spatiotemporal information regarding binding and internalization of
      NBD-labeled gene carriers can be obtained using conventional wide-field
      fluorescence microscopy, since dithionite-mediated quenching of extracellular
      materials reveals the intracellular distribution of gene carriers without the
      need for optical sectioning. Hence, incorporation of environmentally sensitive
      NBD-oligos into gene carriers allows for facile assessment of binding and
      internalization efficiencies of vectors in live cells.

PMID- 18062660
TI  - Cysteinylated protein as reactive disulfide: an alternative route to affinity
      labeling.
AB  - Engineering the permanent formation of a receptor-ligand complex has a number of
      promising applications in chemistry, biology, and medicine. Antibodies and other
      proteins can be excellent receptors for synthetic ligands such as probes or
      drugs. Because proteins possess an array of nucleophilic sites, the placement of
      an electrophile on the synthetic ligand to react with a nucleophile on the
      macromolecule is a standard practice. Previously, we have used the site-directed
      incorporation of cysteine nucleophiles at the periphery of an antibody's binding
      site, paired with the chemical design of weakly electrophilic ligands, to produce
      receptor-ligand pairs that conjugate specifically and permanently (Corneillie et
      al. (2004) Bioconjugate Chem. 15, 1392-1402 and references therein). After
      protein expression in Drosophila S2 cells, we found, as is frequently observed,
      that the engineered cysteine was reversibly blocked by disulfide linkage to a
      cysteine monomer (cysteinylated). Removal of the cysteine monomer requires some
      care because of the need to preserve other disulfide linkages in the protein.
      Here, we report that cysteinylation can be used to advantage by treating the
      cysteine monomer as a leaving group and the protein disulfide as an electrophile
      with special affinity for thiols. Two ligands bearing thiol side chains were
      synthesized and incubated with the cysteinylated antibody Fab fragment 2D12.5
      G54C, with the finding that both ligands become covalently attached within a few
      minutes under physiological conditions. The attachment is robust even in the
      presence of excess thiol reagents. This rapid, specific conjugation is
      particularly interesting for biomedical applications.

PMID- 18062661
TI  - Rational design and generation of a bimodal bifunctional ligand for antibody
      targeted radiation cancer therapy.
AB  - An antibody-targeted radiation therapy (radioimmunotherapy, RIT) employs a
      bifunctional ligand that can effectively hold a cytotoxic metal with clinically
      acceptable complexation kinetics and stability while being attached to a tumor
      specific antibody. Clinical exploration of the therapeutic potential of RIT has
      been challenged by the absence of adequate ligand, a critical component for
      enhancing the efficacy of the cancer therapy. To address this deficiency, the
      bifunctional ligand C-NETA in a unique structural class possessing both a
      macrocyclic cavity and a flexible acyclic moiety was designed. The practical,
      reproducible, and readily scalable synthetic route to C-NETA was developed, and
      its potential as the chelator of (212)Bi, (213)Bi, and (177)Lu for RIT was
      evaluated in vitro and in vivo. C-NETA rapidly binds both Lu(III) and Bi(III),
      and the respective metal complexes remain extremely stable in serum for 14 days.
      (177)Lu -C-NETA and (205/6)Bi -C-NETA possess an excellent or acceptable in vivo
      biodistribution profile.

PMID- 18062662
TI  - SALMON: solvent accessibility, ligand binding, and mapping of ligand orientation
      by NMR spectroscopy.
AB  - Quinone oxidoreductase 2 (NQO2) binds the prodrug tretazicar (also known as
      CB1954, 5-(aziridin-1-yl)-2,4-dinitrobenzamide), which exhibits a profound
      antitumor effect in human cancers when administered together with caricotamide. X
      ray structure determination allowed for two possible orientations of the ligand.
      Here we describe a new NMR method, SALMON (solvent accessibility, ligand binding,
      and mapping of ligand orientation by NMR spectroscopy), based on waterLOGSY to
      determine the orientation of a ligand bound to a protein by mapping its solvent
      accessibility, which was used to unambiguously determine the orientation of
      CB1954 in NQO2.

PMID- 18062663
TI  - Application of 3D-QSAR for identification of descriptors defining bioactivity of
      antimicrobial peptides.
AB  - In our laboratory, a series of antimicrobial peptides have been developed, where
      the resulting 3D-physicochemical properties are controlled by the placement of
      amino acids with well-defined properties (hydrophobicity, charge density,
      electrostatic potential, and so on) at specific locations along the peptide
      backbone. These peptides exhibited different in vitro activity against
      Staphylococcus aureus (SA) and Mycobacterium ranae (MR) bacteria. We hypothesized
      that the differences in the biological activity is a direct manifestation of
      different physicochemical interactions that occur between the peptides and the
      cell membranes of the bacteria. 3D-QSAR analysis has shown that, within this
      series, specific physicochemical properties are responsible for antibacterial
      activity and selectivity. There are five physicochemical properties specific to
      the SA QSAR model, while five properties are specific to the MR QSAR model. These
      results support the hypothesis that, for any particular AMP, organism selectivity
      and potency are controlled by the chemical composition of the target cell
      membrane.

PMID- 18062664
TI  - Endomorphin-2 with a beta-turn backbone constraint retains the potent micro
      opioid receptor agonist properties.
AB  - The constitutional similarity with different secondary structure preference
      between the Aba-Gly and the spiro-Aba-Gly scaffolds were exploited to design the
      novel endomorphin-2 analogs Tyr-spiro-( R/ S)-Aba-Gly-Phe-NH(2) ( 1 and 2) and
      Tyr-( R/ S)-Aba-Gly-Phe-NH(2) ( 3 and 4). The ( R)-spiro analog 1 was found to be
      a potent and selective micro-opioid agonist/partial agonist ( K (imicro) = 29.3
      nM, IC(50) = 50 nM, K(e) = 0.57). NMR experiments and molecular modeling
      indicated that its backbone adopts mainly a beta-turn in aqueous solution.

PMID- 18062665
TI  - Whole genome searching with shotgun proteomic data: applications for genome
      annotation.
AB  - High-throughput genome sequencing continues to accelerate the rate at which
      complete genomes are available for biological research. Many of these new genome
      sequences have little or no genome annotation currently available and hence rely
      upon computational predictions of protein coding genes. Evidence of translation
      from proteomic techniques could facilitate experimental validation of protein
      coding genes, but the techniques for whole genome searching with MS/MS data have
      not been adequately developed to date. Here we describe GENQUEST, a novel method
      using peptide isoelectric focusing and accurate mass to greatly reduce the
      peptide search space, making fast, accurate, and sensitive whole human genome
      searching possible on common desktop computers. In an initial experiment, almost
      all exonic peptides identified in a protein database search were identified when
      searching genomic sequence. Many peptides identified exclusively in the genome
      searches were incorrectly identified or could not be experimentally validated,
      highlighting the importance of orthogonal validation. Experimentally validated
      peptides exclusive to the genomic searches can be used to reannotate protein
      coding genes. GENQUEST represents an experimental tool that can be used by the
      proteomics community at large for validating computational approaches to genome
      annotation.

PMID- 18062667
TI  - Protein identification and Peptide expression resolver: harmonizing protein
      identification with protein expression data.
AB  - Proteomic discovery platforms generate both peptide expression information and
      protein identification information. Peptide expression data are used to determine
      which peptides are differentially expressed between study cohorts, and then these
      peptides are targeted for protein identification. In this paper, we demonstrate
      that peptide expression information is also a powerful tool for enhancing
      confidence in protein identification results. Specifically, we evaluate the
      following hypothesis: tryptic peptides originating from the same protein have
      similar expression profiles across samples in the discovery study. Evidence
      supporting this hypothesis is provided. This hypothesis is integrated into a
      protein identification tool, PIPER (Protein Identification and Peptide Expression
      Resolver), that reduces erroneous protein identifications below 5%. PIPER's
      utility is illustrated by application to a 72-sample biomarker discovery study
      where it is demonstrated that false positive protein identifications can be
      reduced below 5%. Consequently, it is recommended that PIPER methodology be
      incorporated into proteomic studies where both protein expression and
      identification data are collected.

PMID- 18062666
TI  - Metabolomic and proteomic analysis of a clonal insulin-producing beta-cell line
      (INS-1 832/13).
AB  - Metabolites generated from fuel metabolism in pancreatic beta-cells control
      exocytosis of insulin, a process which fails in type 2 diabetes. To identify and
      quantify these metabolites, global and unbiased analysis of cellular metabolism
      is required. To this end, polar metabolites, extracted from the clonal 832/13
      beta-cell line cultured at 2.8 and 16.7 mM glucose for 48 h, were derivatized
      followed by identification and quantification, using gas chromatography (GC) and
      mass spectrometry (MS). After culture at 16.7 mM glucose for 48 h, 832/13 beta
      cells exhibited a phenotype reminiscent of glucotoxicity with decreased content
      and secretion of insulin. The metabolomic analysis revealed alterations in the
      levels of 7 metabolites derived from glycolysis, the TCA cycle and pentose
      phosphate shunt, and 4 amino acids. Principal component analysis of the
      metabolite data showed two clusters, corresponding to the cells cultured at 2.8
      and 16.7 mM glucose, respectively. Concurrent changes in protein expression were
      analyzed by 2-D gel electrophoresis followed by LC-MS/MS. The identities of 86
      spots corresponding to 75 unique proteins that were significantly different in
      832/13 beta-cells cultured at 16.7 mM glucose were established. Only 5 of these
      were found to be metabolic enzymes that could be involved in the metabolomic
      alterations observed. Anticipated changes in metabolite levels in cells exposed
      to increased glucose were observed, while changes in enzyme levels were much less
      profound. This suggests that substrate availability, allosteric regulation,
      and/or post-translational modifications are more important determinants of
      metabolite levels than enzyme expression at the protein level.

PMID- 18062669
TI  - Evaluation of minimal Trichoderma reesei cellulase mixtures on differently
      pretreated Barley straw substrates.
AB  - The commercial cellulase product Celluclast 1.5, derived from Trichoderma reesei
      (Novozymes A/S, Bagsvaerd, Denmark), is widely employed for hydrolysis of
      lignocellulosic biomass feedstocks. This enzyme preparation contains a broad
      spectrum of cellulolytic enzyme activities, most notably cellobiohydrolases
      (CBHs) and endo-1,4-beta-glucanases (EGs). Since the original T. reesei strain
      was isolated from decaying canvas, the T. reesei CBH and EG activities might be
      present in suboptimal ratios for hydrolysis of pretreated lignocellulosic
      substrates. We employed statistically designed combinations of the four main
      activities of Celluclast 1.5, CBHI, CBHII, EGI, and EGII, to identify the optimal
      glucose-releasing combination of these four enzymes to degrade barley straw
      substrates subjected to three different pretreatments. The data signified that
      EGII activity is not required for efficient lignocellulose hydrolysis when
      addition of this activity occurs at the expense of the remaining three
      activities. The optimal ratios of the remaining three enzymes were similar for
      the two pretreated barley samples that had been subjeced to different hot water
      pretreatments, but the relative levels of EGI and CBHII activities required in
      the enzyme mixture for optimal hydrolysis of the acid-impregnated, steam-exploded
      barley straw substrate were somewhat different from those required for the other
      two substrates. The optimal ratios of the cellulolytic activities in all cases
      differed from that of the cellulases secreted by T. reesei. Hence, the data
      indicate the feasibility of designing minimal enzyme mixtures for pretreated
      lignocellulosic biomass by careful combination of monocomponent enzymes. This
      strategy can promote both a more efficient enzymatic hydrolysis of
      (ligno)cellulose and a more rational utilization of enzymes.

PMID- 18062670
TI  - Impairing and monitoring glucose catabolite repression in L-carnitine
      biosynthesis.
AB  - Signal transduction pathways are usually avoided when optimizing a
      biotransformation process because they require complex mathematical formulations.
      The aim of this work was to use a Systems Biology approach to optimize and
      monitor the biotransformation of L-carnitine using signal transduction pathways.
      To this end, a dynamic model was constructed, integrating the metabolic pathways
      of L-carnitine biosynthesis as well as the expression of this metabolism by means
      of its regulation by transcription factors such as cAMP-CRP and CaiF. The model
      was validated using different C-sources as well as different reactor feeding
      approaches. A linear relationship between the external cellular cAMP and the L
      carnitine production levels was predicted before being experimentally confirmed
      in several scenarios. Moreover, results of the model simulations and subsequent
      experimental findings demonstrated that the addition of exogenous cAMP was able
      to restore the L-carnitine production when glucose was used as C-source.
      Additionally, a way to monitor the L-carnitine biosynthesis by using the level of
      cAMP as a marker of the biotransformation state was in silico and experimentally
      demonstrated.

PMID- 18062671
TI  - Solid-supported nitroso hetero diels-alder reactions. 2. Arylnitroso dienophiles:
      scope and limitations.
AB  - Immobilized arylnitroso dienophiles were prepared and used in hetero Diels-Alder
      (HDA) reactions with a variety of dienes. Polymer-supported arylnitroso species
      were prepared on several linkers cleavable by different cleavage reagents and
      used for (i) optimization of reaction conditions for HDA reactions, (ii)
      evaluation of the reaction outcome with various dienes, (iii) comparison of
      relative reactivities of dienes, and (iv) assessment of the stability of HDA
      adducts toward cleavage conditions typically used in solid-phase preparation
      (TFA). The outcome of the HDA reactions has been evaluated for a set of 19
      dienes, and the relative reactivities of dienes that yielded the expected HDA
      adducts were compared. Cleaved products were submitted to biological assays, and
      the results are reported.

PMID- 18062672
TI  - Assembly of a three-dimensional array of glycoconjugates by combinatorial
      biocatalysis in nonaqueous media.
AB  - Glycoconjugates can be artificially synthesized by combinatorial biocatalysis. An
      example is given in this paper describing the construction of glycoconjugates
      array by using glycosidase and lipase in nonaqueous media. This array was started
      from glucose, with three aryl alcohols as the aglycone moiety of glycosides and
      five acids or esters as acyl donors for combinatorial acylation of glycosides,
      affording a three-dimensional array containing about 30 members with diverse
      structures. The array would be more abundant if more aglycones and acyl donors
      with other structures were filled in. Indeed, diverse classes of carbohydrates
      besides glucose can also be employed for generating diverse glycoconjugates due
      to their different roles in numerous physiological responses. The composition and
      distribution of the demonstration glycoconjugates array was detected and
      evaluated by HPLC-MS with electrospray ionization. And also, the distribution of
      the artificial array can be adjusted by changing the molar ratio of the auxiliary
      materials.

PMID- 18062673
TI  - Formation of substituted pyrroles via an imine condensation/Aza-Claisen
      rearrangement/imine-allene cyclization process by MAOS.
AB  - A diverse collection of pyrroles has been prepared using a one-pot, domino
      aldehyde/amine condensation, [3,3]-aza-Claisen rearrangement, imine-allene
      cyclization strategy. This protocol was accelerated by microwave irradiation and
      provided very good levels of conversion after reacting for only 30 min.

PMID- 18062674
TI  - A comparison of mainstream and sidestream marijuana and tobacco cigarette smoke
      produced under two machine smoking conditions.
AB  - The chemical composition of tobacco smoke has been extensively examined, and the
      presence of known and suspected carcinogens in such smoke has contributed to the
      link between tobacco smoking and adverse health effects. The consumption of
      marijuana through smoking remains a reality and, among youth, seems to be
      increasing. There have been only limited examinations of marijuana smoke,
      including for cannabinoid content and for tar generation. There have not been
      extensive studies of the chemistry of marijuana smoke, especially in direct
      comparison to tobacco smoke. In this study, a systematic comparison of the smoke
      composition of both mainstream and sidestream smoke from marijuana and tobacco
      cigarettes prepared in the same way and consumed under two sets of smoking
      conditions, was undertaken. This study examined the suite of chemicals routinely
      analyzed in tobacco smoke. As expected, the results showed qualitative
      similarities with some quantitative differences. In this study, ammonia was found
      in mainstream marijuana smoke at levels up to 20-fold greater than that found in
      tobacco. Hydrogen cyanide, NO, NO x , and some aromatic amines were found in
      marijuana smoke at concentrations 3-5 times those found in tobacco smoke.
      Mainstream marijuana smoke contained selected polycyclic aromatic hydrocarbons
      (PAHs) at concentrations lower than those found in mainstream tobacco smoke,
      while the reverse was the case for sidestream smoke, with PAHs present at higher
      concentrations in marijuana smoke. The confirmation of the presence, in both
      mainstream and sidestream smoke of marijuana cigarettes, of known carcinogens and
      other chemicals implicated in respiratory diseases is important information for
      public health and communication of the risk related to exposure to such
      materials.

PMID- 18062675
TI  - Composite polyacrylate-poly(3,4- ethylenedioxythiophene) membranes for improved
      all-solid-state ion-selective sensors.
AB  - A novel type of self-plasticizing polyacrylate-based membrane was developed for
      all-solid-state ion-selective potentiometric electrodes. The membrane composition
      contains a conducting polymer (CP): poly(3,4-ethylenedioxythiophene) end capped
      with methacrylate groups, chemically grafted with the membrane during the
      photopolymerization step. This composition results in ion-selective membranes
      with the following advantages: lower electrical resistance compared to the CP
      free membrane, facile ion-to-electron transduction between the membrane and the
      electrode support, controlled low activity of analyte ions, and high
      concentration of interferent ions (incorporated with the CP) within the membrane,
      potentially resulting in improved analytical parameters. Ca2+- and K+-selective
      membranes were chosen as model systems to study the effect of pretreatment and CP
      content on the potentiometric sensor's characteristics. For Ca2+ sensors,
      reproducible and stable Nernstian characteristics were obtained within the range
      from 0.1 to 10(-9) M CaCl2, without a time-consuming preconditioning step. For K+
      selective sensors, the influence on Nernstian response range was observed for
      varying KCl concentrations in the conditioning solution, with the lowest
      detection limit found close to 10(-8) M KCl. Mass spectrometry coupled with laser
      ablation studies of the membranes revealed that in this case the detection limit
      is not related to primary ion content in the membrane contacting a sample
      solution, but is affected by interfering ion concentration close to the membrane
      surface.

PMID- 18062676
TI  - Complete removal of chlorinated aromatic compounds from oils by channel-type
      gamma-cyclodextrin assembly.
AB  - This paper describes the complete removal of chlorinated aromatic compounds from
      insulating oil by a channel-type gamma-cyclodextrin (gamma-CD) assembly as a new
      adsorbent. Using this type of adsorbent (50-60 wt % of oil), 1,2,4- and 1,3,5
      trichlorobenzenes, 2- and 4-chlorobiphenyls (2- and 4-MCBs), 4,4'
      dichlorobiphenyl (4,4'-DiCB), and 3,4,4'-trichlorobiphenyl (3,4,4'-TrCB), whose
      initial concentrations were 100 ppm, were completely removed from the insulating
      oil. Competitive adsorption experiments using a mixture of 2-MCB and 4-MCB or a
      mixture of 4-MCB, 4,4'-DiCB, and 3,4,4'-TrCB revealed that selective adsorption
      based on the shape and size of the chlorinated aromatics was achieved by the
      channel-type gamma-CD assembly, implying that inclusion into the cavity of the
      channel-type gamma-CD was responsible for the removal of chlorinated aromatics
      from insulating oil. It was also found that more than 70% of adsorbed chlorinated
      aromatics was easily recovered from the channel-type gamma-CD by simply washing
      with n-hexane, and chlorinated aromatics were completely removed from the
      insulating oil even by the regenerated adsorbent, indicating that the gamma-CD
      assembly can be easily regenerated and recycled.

PMID- 18062677
TI  - Ozone-induced dissociation: elucidation of double bond position within mass
      selected lipid ions.
AB  - Ions formed from lipids during electrospray ionization of crude lipid extracts
      have been mass-selected within a quadrupole linear ion trap mass spectrometer and
      allowed to react with ozone vapor. Gas-phase ion-molecule reactions between
      unsaturated lipid ions and ozone are found to yield two primary product ions for
      each carbon-carbon double bond within the molecule. The mass-to-charge ratios of
      these chemically induced fragments are diagnostic of the position of unsaturation
      within the precursor ion. This novel analytical technique, dubbed ozone-induced
      dissociation (OzID), can be applied both in series and in parallel with
      conventional collision-induced dissociation (CID) to provide near-complete
      structural assignment of unknown lipids within complex mixtures without prior
      fractionation or derivatization. In this study, OzID is applied to a suite of
      complex lipid extracts from sources including human lens, bovine kidney, and
      commercial olive oil, thus demonstrating the technique to be applicable to a
      broad range of lipid classes including both neutral and acidic
      glycerophospholipids, sphingomyelins, and triacylglycerols. Gas-phase ozonolysis
      reactions are also observed with different types of precursor ions including
      [M+H]+, [M+Li]+, [M+Na]+, and [M-H]-: in each case yielding fragmentation data
      that allow double bond position to be unambiguously assigned. Within the human
      lens lipid extract, three sphingomyelin regioisomers, namely SM(d18:0/15Z-24:1),
      SM(d18:0/17Z-24:1), and SM(d18:0/19Z-24:1), and a novel phosphatidylethanolamine
      alkyl ether, GPEtn(11Z-18:1e/9Z-18:1), are identified using a combination of CID
      and OzID. These discoveries demonstrate that lipid identification based on CID
      alone belies the natural structural diversity in lipid biochemistry and
      illustrate the potential of OzID as a complementary approach within automated,
      high-throughput lipid analysis protocols.

PMID- 18062678
TI  - Thermal decomposition of CF3 and the reaction of CF2 + OH --> CF2O + H.
AB  - The reflected shock tube technique with multipass absorption spectrometric
      detection (at a total path length of approximately 1.75 m) of OH-radicals at 308
      nm has been used to study the dissociation of CF3-radicals [CF3 + Kr --> CF2 + F
      + Kr (a)] between 1,803 and 2,204 K at three pressures between approximately 230
      and 680 Torr. The OH-radical concentration buildup resulted from the fast
      reaction F + H2O --> OH + HF (b). Hence, OH is a marker for F-atoms. To extract
      rate constants for reaction (a), the [OH] profiles were modeled with a chemical
      mechanism. The initial rise in [OH] was mostly sensitive to reactions (a) and
      (b), but the long time values were additionally affected by CF2 + OH --> CF2O + H
      (c). Over the experimental temperature range, rate constants for (a) and (c) were
      determined from the mechanistic fits to be kCF3+Kr = 4.61 x 10-9 exp(-30,020 K/T)
      and kCF2+OH = (1.6 +/- 0.6) x 10-10, both in units of cm3 molecule-1 s-1.
      Reaction (a), its reverse recombination reaction reaction (-a), and reaction (c)
      are also studied theoretically. Reactions (c) and (-a) are studied with direct
      CASPT2 variable reaction coordinate transition state theory. A master equation
      analysis for reaction (a) incorporating the ab initio determined reactive flux
      for reaction (-a) suggests that this reaction is close to but not quite in the
      low-pressure limit for the pressures studied experimentally. In contrast,
      reaction (c) is predicted to be in the high-pressure limit due to the high
      exothermicity of the products. A comparison with past and present experimental
      results demonstrates good agreement between the theoretical predictions and the
      present data for both (a) and (c).

PMID- 18062679
TI  - Single-walled carbon nanotube binding peptides: probing tryptophan's importance
      by unnatural amino acid substitution.
AB  - Peptides selected from phage-displayed libraries have been found to exhibit high
      affinity binding to carbon nanotubes including single-walled carbon nanotubes
      (SWNTs), multi-walled carbon nanotubes, and single-walled carbon nanohorns. One
      unique feature of these peptides is that their amino acid sequences are rich in
      tryptophan and histidine residues. The aim of this study was to investigate the
      importance of the tryptophan residue in a newly identified SWNT-binding peptide,
      UW-1, which contains the motif, XTHXXPWTX, where X is any amino acid. Tryptophan
      was altered in the following ways: mutation to alanine or substitution with three
      unnatural tryptophan analogues, i.e., 5-fluorotryptophan, 5-hydroxytryptophan,
      and 7-azatryptophan. Analysis of experimental and computational data suggests
      that the highest occupied molecular orbital of the tryptophan residue in the
      peptide interacts with the lowest unoccupied molecular orbital from the SWNT.
      This information should be important in permitting modulation of peptide
      affinities to these nanomaterials.

PMID- 18062680
TI  - Solvation of calcium ions in methanol-water mixtures: molecular dynamics
      simulation.
AB  - Molecular dynamics simulations of CaCl2 solutions in water and methanol-water
      mixtures, with methanol concentrations of 5, 10, 50, and 90 mol %, at room
      temperature, have been performed. The methanol and water molecules have been
      modeled as flexible three-site bodies. Solvation of the calcium ions has been
      discussed on the basis of the radial and angular distribution functions, the
      orientation of the solvent molecules, and their geometrical arrangement in the
      coordination shells. Analysis of the H-bonds of the solvent molecules coordinated
      by Ca2+ has been done. Residence time of the solvent molecules in the
      coordination shell has been calculated. The preferential hydration of the calcium
      ions has been found over the whole range of the mixture composition. The water
      concentration in the first and second coordination shells of Ca2+ significantly
      exceeds the water content in the solution, despite the very similar interaction
      energy of the calcium ion with water and methanol. In aqueous solution and
      methanol-water mixtures, the first coordination shell of Ca2+ is irregular and
      long-living. The solvent molecules prefer the anti-dipole arrangement, but, in
      aqueous solutions and water-rich mixtures, the water molecules in the primary
      shell have only one H-bonded neighbor.

PMID- 18062681
TI  - Role of multivalent cations in the self-assembly of phospholipid-DNA complexes.
AB  - In view of efficient and nontoxic delivery of genes to cells, complexes made of
      phospholipids (noncationic) and DNA are assembled through the mediation of
      multivalent cations. The association of lipids with DNA is explained through the
      charge reversal of lipid headgroups by specific adsorption of cations. The ion
      binding is quantified by the Gouy-Chapman-Stern theory which provides a good
      estimate for the minimal concentration of cations required to produce complexes.
      Coarse-grained Monte Carlo calculations support X-ray diffraction experiments in
      the sense that lipids form inverted micelles around hexagonally arranged DNA
      rods, with cations in between to maintain the cohesion. The complexes are more
      cohesive in terms of total free energy as the cation valence increases. The
      presented methodology may help develop predictive models for biomolecular self
      assembled systems.

PMID- 18062682
TI  - Characterization of temperature-dependent iron-imidazole vibrational modes in far
      infrared.
AB  - The active site of several oxygen binding proteins can be mimicked with the
      ferric iron protoporphyrin IX derivative hemin, coordinating two imidazole
      molecules and embedded in sodium dodecyl sulfate (SDS) micelles; the detergent
      simulates the hydrophobic cavity of heme proteins. We studied the low-frequency
      vibrational modes of the porphyrin-iron-imidazole bonding in infrared absorbance
      spectra. Assignment of the metal-ligand vibrations to signals at 396, 387, and
      378 cm(-1) was performed by isotope labeling of the imidazole ligand. These modes
      were also found to be temperature-dependent and to display a linear increase of
      signal intensity between 25 and 150 K and, with a different slope, between 150
      and 300 K. The modes at 396 and 399 cm(-1) show for 25 K an up-shift about 4 cm(
      1) and the signal at 378 cm(-1) a small downshift, indicating the involvement of
      antisymmetric stretching modes and, in the latter, of bending motions. Anharmonic
      couplings to doming modes are discussed, and the doming mode and hydrogen-bonding
      signature spectral range between 300 and 100 cm(-1) is presented.

PMID- 18062683
TI  - Stabilization of methane hydrate by pressurization with He or N2 gas.
AB  - The behavior of methane hydrate was investigated after it was pressurized with
      helium or nitrogen gas in a test system by monitoring the gas compositions. The
      results obtained indicate that even when the partial pressure of methane gas in
      such a system is lower than the equilibrium pressure at a certain temperature,
      the dissociation rate of methane hydrate is greatly depressed by pressurization
      with helium or nitrogen gas. This phenomenon is only observed when the total
      pressure of methane and helium (or nitrogen) gas in the system is greater than
      the equilibrium pressure required to stabilize methane hydrate with just methane
      gas. The following model has been proposed to explain the observed phenomenon:
      (1) Gas bubbles develop at the hydrate surface during hydrate dissociation, and
      there is a pressure balance between the methane gas inside the gas bubbles and
      the external pressurizing gas (methane and helium or nitrogen), as transmitted
      through the water film; as a result the methane gas in the gas bubbles stabilizes
      the hydrate surface covered with bubbles when the total gas pressure is greater
      than the equilibrium pressure of the methane hydrate at that temperature; this
      situation persists until the gas in the bubbles becomes sufficiently dilute in
      methane or until the surface becomes bubble-free. (2) In case of direct contact
      of methane hydrate with water, the water surrounding the hydrate is
      supersaturated with methane released upon hydrate dissociation; consequently,
      methane hydrate is stabilized when the hydrostatic pressure is above the
      equilibrium pressure of methane hydrate at a certain temperature, again until the
      dissolved gas at the surface becomes sufficiently dilute in methane. In essence,
      the phenomenon is due to the presence of a nonequilibrium state where there is a
      chemical potential gradient from the solid hydrate particles to the bulk solution
      that exists as long as solid hydrate remains.

PMID- 18062684
TI  - Characterizing nitrilimines with nuclear magnetic resonance spectroscopy. A
      theoretical study.
AB  - The 13C chemical shifts in selected nitrilimines, nitriles, acetylenes, allenes,
      and singlet carbenes have been calculated using density-functional theory [PBE0/6
      311++G(2df,pd)] and the gauge including atomic orbital (GIAO) method. The effects
      of substitution on the 13C chemical shifts in nitrilimines, R1-CNN-R2, have been
      examined. The carbon nucleus is generally found to be deshielded by substituents
      in the order CH3 < NH2 < OH < F. Comparison with nitriles, acetylenes, and
      allenes shows that this effect is related to the presence of the cumulated
      functionality, C=N=N. Terminal N-substitution is found to have a larger effect
      than C-substitution due to a large increase in chemical shielding anisotropy. The
      electronic structure of nitrilimines has recently been shown to possess a carbene
      component whose resonance contribution varies widely with substitution, and, as
      previously reported, insight into the electronic structure can be gained by an
      analysis of the shielding tensor, especially for carbenes. Accordingly, the
      components of the diagonalized 13C shielding tensor for nitrilimines and stable
      singlet carbenes have been examined. This analysis suggests that
      diaminonitrilimine, H2N-CNN-NH2, may be a stable carbene, and, to the best of our
      knowledge, it would be the first acyclic, unsaturated stable carbene ever
      reported. Finally, a detailed analysis of the 13C chemical shifts shows that an
      increase in the dipolar character of nitrilimines induces a shielding at the
      carbon nucleus, while an increase in allenic or carbenic character tends to cause
      a deshielding.

PMID- 18062685
TI  - Synthesis, characterization, and in vitro evaluation of a potentially selective
      anticancer, mixed-metal [ruthenium(III)-platinum(II)] trinuclear complex.
AB  - A new type of mixed-metal trinuclear complex containing platinum(II) and
      ruthenium(III) fragments that resemble both cisplatin and NAMI-A has been
      synthesized and characterized by IR, 1H NMR, elemental analysis, and X-ray
      crystallography. The water-soluble compound Na2{trans,cis,trans-[RuIIICl4(DMSO
      S)(mu-pyz)]2PtIICl2} (AH-197, pyz = pyrazine) was assessed for its effects on DNA
      mobility and toxicity against human cancer cell lines. When compared to cisplatin
      and KP-1019 (which structurally resembles NAMI-A), IC50 results showed that AH
      197 had an intermediate toxicity. When this data was coupled with a subsequent
      COMPARE evaluation (standard COMPARE queries resulted in insignificant
      correlation coefficients (<0.70) while very low COMPARE correlation coefficients
      were found in the matrix queries as well), AH-197 yielded a correlation
      coefficient of 0.19 when compared to cisplatin and 0.25 when compared to KP1019
      indicating that AH-197 has a unique behavior.

PMID- 18062686
TI  - Comparative studies on exchange reactions of hexafluoroacetylacetonate in
      bis(hexafluoroacetylacetonato)(dimethyl sulfoxide)dioxouranium(VI) in nonaqueous
      solvent and supercritical CO(2).
AB  - Exchange reactions of hexafluoroacetylacetonate (hfacac) in UO2(hfacac)2DMSO
      (DMSO = dimethyl sulfoxide) in o-C6D4Cl2 and supercritical CO2 (sc-CO2) have been
      studied using the NMR line-broadening method to compare reactivity in a
      nonaqueous solvent with that in sc-CO2. It was found that the exchange rates of
      hfacac in both systems are dependent on the concentration of the enol isomer
      ([Henol]) of hexafluoroacetylacetone and become slow with an increase in the
      concentration of free DMSO ([DMSO]). The exchange reaction between free and
      coordinated DMSO in UO2(hfacac)2DMSO has been also examined in o-C6D4Cl2 and sc
      CO2. As a result, the exchange rate of DMSO was found to depend on [DMSO]. From
      these results, the hfacac exchange reactions in UO2(hfacac)2DMSO in o-C6D4Cl2 and
      sc-CO2 were proposed to proceed through the mechanism that the ring-opening for
      one of two coordinated hfacac in UO2(hfacac)2DMSO is the rate-determining step,
      and the resulting vacant site is coordinated by the incoming Henol, followed by
      the proton transfer from Henol to hfacac and the ring closure of unidentate
      hfacac. The rate constants at 60 degrees C and the activation parameters (DeltaH
      and DeltaS) for the ring-opening path are 35.8 +/- 3.2 s(-1), 57.8 +/- 2.7
      kJ.mol(-1), and -42.9 +/- 7.7 J.mol(-1).K(-1) for the o-C6D4Cl2 system, and 518
      +/- 50 s(-1), 18.9 +/- 1.8 kJ.mol(-1), and -138 +/- 5 J.mol(-1).K(-1) for the sc
      CO2 system, respectively. Differences in kinetic parameters between sc-CO2 and o
      C6D4Cl2 systems were proposed to be attributed to the solute-solvent interactions
      such as Lewis acid-Lewis base interactions and hydrogen bondings between sc-CO2
      and beta-diketones.

PMID- 18062687
TI  - Solventless nanoparticles synthesis under low pressure.
AB  - In the present study, metal nanocrystals were obtained by the very easy,
      economical, and nontoxic thermal decomposition method and stabilized by coating
      oleate without any solvent. These nanocrystals have a highly crystalline
      structure due to a high decomposition temperature (~563-573 K) at low pressure
      and very narrow distribution. The prepared Fe3O4 nanocrystals were controlled by
      the annealing time and vacuum pressure. A TEM image of monodispersed Fe3O4
      nanocrystals showed the 2D assembly of nanocrystals, demonstrating their
      uniformity. The particle size is 10.6 +/- 1.2 nm. TEM images of silver
      nanocrystals a showed 2D assembly with 9.5 +/- 0.7 nm. An electron diffraction
      image and X-ray diffraction of the nanocrystals showed the highly crystalline
      nature of metal nanocrystals.

PMID- 18062688
TI  - Synthesis of a new ligand for transition metal-fullerene supramolecular systems.
AB  - A new ligand has been designed that provides a relatively simple framework to
      build supramolecular systems containing both fullerene and transition-metal
      moieties. The modular framework of the ligand allows for the easy design of more
      complex systems. Analysis of absorption and emission spectra suggests significant
      photoinduced charge transfer between the two moieties. More complex systems and
      the excited-state photophysics of the presented systems are being studied.

PMID- 18062689
TI  - Electronic structure description of the cis-MoOS unit in models for molybdenum
      hydroxylases.
AB  - The molybdenum hydroxylases catalyze the oxidation of numerous aromatic
      heterocycles and simple organics and, unlike other hydroxylases, utilize water as
      the source of oxygen incorporated into the product. The electronic structures of
      the cis-MoOS units in CoCp2[TpiPrMoVOS(OPh)] and TpiPrMoVIOS(OPh) (TpiPr =
      hydrotris(3-isopropylpyrazol-1-yl)borate), new models for molybdenum
      hydroxylases, have been studied in detail using S K-edge X-ray absorption
      spectroscopy, vibrational spectroscopy, and detailed bonding calculations. The
      results show a highly delocalized Mo=S pi* LUMO redox orbital that is formally
      Mo(dxy) with approximately 35% sulfido ligand character. Vibrational spectroscopy
      has been used to quantitate Mo-Ssulfido bond order changes in the cis-MoOS units
      as a function of redox state. Results support a redox active molecular orbital
      that has a profound influence on MoOS bonding through changes to the relative
      electro/nucleophilicity of the terminal sulfido ligand accompanying oxidation
      state changes. The bonding description for these model cis-MoOS systems supports
      enzyme mechanisms that are under orbital control and dominantly influenced by the
      unique electronic structure of the cis-MoOS site. The electronic structure of the
      oxidized enzyme site is postulated to play a role in polarizing a substrate
      carbon center for nucleophilic attack by metal activated water and acting as an
      electron sink in the two-electron oxidation of substrates.

PMID- 18062690
TI  - Cyclometalated iridium(III) Aquo complexes: efficient and tunable catalysts for
      the homogeneous oxidation of water.
AB  - A series of bis-phenylpyridine, bis-aquo iridium(III) complexes is herein shown
      to robustly and efficiently catalyze the oxidation of water to dioxygen in the
      presence of a sacrificial oxidant. Through substitution on the cyclometalating
      ligands of these complexes, it is shown that a broad range of oxidation
      potentials can be achieved within this class of catalyst. Parallel, dynamic
      monitoring of oxygen evolution, made possible by equipping reaction vessels with
      pressure-voltage transducers, facilitates correlation of these complexes'
      ionization potentials with their respective activity toward water oxidation. The
      importance of these catalysts lies in (A) their ability to oxidize water in a
      purely aqueous medium, (B) their simplicity of design, (C) their durability, and
      (D) the ease with which they can be tuned to accommodate the electrochemical
      needs of photosensitizers in hypothetical photochemical water oxidation and full
      artificial photosynthetic schemes.

PMID- 18062691
TI  - Facile access to pyrazolines via domino reaction of the Huisgen zwitterions with
      aziridines.
AB  - A novel, efficient, and general domino reaction of 2-acylaziridines with the
      Huisgen zwitterions to furnish 2-pyrazoline rings is described. A possible
      mechanism for the domino sequence is proposed.

PMID- 18062692
TI  - Intramolecular Diels-Alder/Tsuji allylation assembly of the functionalized trans
      decalin of salvinorin A.
AB  - An enantioselective synthesis of the highly functionalized trans-decalin core (2)
      of salvinorin A is described. The tetraene 4 was synthesized in six steps from a
      known L-(+)-tartaric acid derivative. Three contiguous stereocenters, two of them
      quaternary, on the trans-decalin were established asymmetrically by an
      intramolecular Diels-Alder/Tsuji allylation sequence.

PMID- 18062693
TI  - Progress toward the synthesis of the basiliolides and transtaganolides: an
      intramolecular pyrone Diels-Alder entry into a novel class of natural products.
AB  - Efforts directed toward the synthesis of a basiliolide/transtaganolide model
      system are disclosed. A highly endo-selective intramolecular pyrone Diels-Alder
      (IMPDA) cycloaddition rapidly constructs the tricyclic core of the basiliolides
      and transtaganolides.

PMID- 18062694
TI  - A highly selective fluorescent probe for thiol bioimaging.
AB  - A new fluorescent turn-on probe (3) for the selective sensing and bioimaging of
      thiols is reported. In aqueous buffer solutions at physiological pH, thiols
      cleave the 2,4-dinitrobenzenesulfonyl group to release the red-emissive donor
      acceptor fluorophore (4). The probe displays excellent immunity to interference
      from nitrogen and oxygen nucleophiles and the imaging of thiols in living cells
      is demonstrated.

PMID- 18062695
TI  - A multifaceted phosphate tether: application to the C1-C14 subunit of dolabelides
      A-D.
AB  - A phosphate tether approach to the C1-14 subunit of dolabelide is described. The
      phosphate tether serves a multifaceted role mediating several processes,
      including (i) diastereotopic differentiation via RCM, (ii) selective CM by
      imparting Type III behavior to the exocyclic olefin, (iii) regioselective
      hydrogenation, and (iv) regioselective Pd(0)-catalyzed reductive opening of the
      bicyclic phosphate. Overall, this strategy uses orthogonal protecting- and
      leaving-group properties innate to phosphate esters to rapidly assembly the
      titled subunit.

PMID- 18062696
TI  - Electrochemical quartz crystal microbalance studies on enzymatic specific
      activity and direct electrochemistry of immobilized glucose oxidase in the
      presence of sodium dodecyl benzene sulfonate and multiwalled carbon nanotubes.
AB  - The electrochemical quartz crystal microbalance (EQCM) technique was utilized to
      monitor in situ the adsorption of glucose oxidase (GOD) and the mixture of GOD
      and sodium dodecyl benzene sulfonate (SDBS) onto Au electrodes with and without
      modification of multiwalled carbon nanotubes (MWCNTs) or SDBS/MWCNTs composite,
      and the relationship between enzymatic specific activity (ESA) and direct
      electrochemistry of the immobilized GOD was quantitatively evaluated for the
      first time. Compared with the bare gold electrode at which a little GOD was
      adsorbed and the direct electrochemistry of the adsorbed GOD was negligible, the
      amount and electroactivity of adsorbed GOD were greatly enhanced when the GOD was
      mixed with SDBS and then adsorbed onto the SDBS/MWCNTs modified Au electrode.
      However, the ESA of the adsorbed GOD was fiercely decreased to only 16.1% of the
      value obtained on the bare gold electrode, and the portion of adsorbed GOD
      showing electrochemical activity exhibited very low enzymatic activity,
      demonstrating that the electroactivity and ESA of immobilized GOD responded
      oppositely to the presence of MWCNTs and SDBS. The ESA results obtained from the
      EQCM method were well supported by conventional UV-vis spectrophotometry. The
      direct electrochemistry of redox proteins including enzymes as a function of
      their biological activities is an important concern in biotechnology, and this
      work may have presented a new and useful protocol to quantitatively evaluate both
      the electroactivity and ESA of trace immobilized enzymes, which is expected to
      find wider applications in biocatalysis and biosensing fields.

PMID- 18062697
TI  - Self-assembly of noncyclic bis-D- and L-tripeptides into higher order tubular
      constructs: design, synthesis, and X-ray crystal superstructure.
AB  - Trans (1R,2R)-diaminocyclohexane was used as a semirigid vicinal diamine to
      anchor two N-protected tripeptides consisting of L-D-L amino acids as carboxy
      terminal amides. The bis-tripeptide consisting of L-Ser (OBn)-D-Ser (OBn)-L-Ser
      (O-p-bromobenzyl) Boc afforded X-ray quality crystals containing benzene and
      chloroform solvent molecules. Analysis of the solid-state structure revealed a
      highly H-bonded helical open-ended tubular superstructure. The tripeptide strands
      intertwine like a pair of self-embracing arms, held together by a gamma-turn and
      a 14-membered antiparallel H-bonded macroring spanning the first and third amino
      acid residues within each strand. Whereas the tripeptide from the R,R anchor gave
      beautiful crystals from benzene and chloroform, the analogous construct from the
      S,S-anchored diamine gave a gel. Related bis-tripeptides with different amino
      acids showed extensive intramolecular H-bonding based on NMR titration and
      dilution experiments.

PMID- 18062698
TI  - Computational studies of the tropone natural products, thiotropocin,
      tropodithietic acid, and troposulfenin. Significance of thiocarbonyl-enol
      tautomerism.
AB  - Computations provide insight to the stability and isomeric possibilities of
      thiotropocin, tropodithietic acid, and troposulfenin. Thiotropocin and
      tropodithietic acid contain a flat 7-membered ring and delocalized pi-bonds
      similar to those of tropylium ion (C(7)H(7)(+)). Troposulfenin is far less
      stable; it contains a puckered tropone ring and localized bonds similar to 1,3,5
      cycloheptatriene. A facile 1,5-hydrogen shift suggests that thiotropocin and
      tropodithietic acid exist as a pair of interconverting tautomers. Loss of an
      acidic proton from these three tautomers produces the same conjugate base
      structure.

PMID- 18062699
TI  - Optical resolution of (+/-)-1,2-Bis(2-methylphenyl)ethylene-1,2-diamine as a
      chiral framework for 2-iminoimidazolidine with 2-methylphenyl pendant and the
      guanidine-catalyzed asymmetric michael reaction of tert-butyl
      diphenyliminoacetate and ethyl acrylate.
AB  - (+/-)-1,2-Bis(2-methylphenyl)ethylene-1,2-diamine, prepared from benzil and
      ammonium acetate, was optically resolved as a chiral framework for 2-(1-benzyl-2
      hydroxyethyl)imino-1,3-dimethylimidazolidine with 2-methylphenyl pendants at the
      4,5-positions. Catalysis ability of the 1,3-dimethyl-4,5-bis(2
      methylphenyl)imidazolidine and the related 1,3-dibenzyl-4,5-diphenylimidazolidine
      was examined in the asymmetric Michael reaction of t-butyl diphenyliminoacetate
      and ethyl acrylate.

PMID- 18062700
TI  - Ureidobenzotriazine multiple H-bonding arrays: the importance of geometrical
      details on the stability of H-bonds.
AB  - A 3-ureidobenzo-1,2,4-triazine 1-N-oxide (1) was synthesized successfully. The
      derivative displays an acceptor-donor-acceptor-acceptor (ADAA) hydrogen-bonding
      motif in CDCl(3) and DMSO-d(6) solution as well as in the solid state. Although
      moderately strong association of 1 was observed with DAD motifs, nonspecific
      binding is observed with ureidopyridines featuring a complementary DADD array.
      Density functional calculations of conformations 1a and 1b together with two
      complexes revealed the clearly nonplanar geometry of the multiply hydrogen-bonded
      complex, in which some bonds are significantly longer (3.2 A) than is optimal for
      H-bonds. As a result, only very small free energies of association were
      calculated, in line with the experimentally observed absence of specific assembly
      of the components.

PMID- 18062701
TI  - Evaluation of enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol for
      catalytic asymmetric addition of organozinc reagents to aldehydes.
AB  - A facile and practical approach to preparation of enantiopure N
      (ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol was developed from cheap and
      easily available l-(+)-methionine. Synthetic highlights include the three-step,
      one-pot construction of the chiral azetidine ring and the development of an
      improved one-step procedure for the synthesis of the key intermediate l-2-amino-4
      bromobutanoic acid. Enantiopure N-(ferrocenylmethyl)azetidin-2
      yl(diphenyl)methanol was evaluated for catalytic asymmetric addition of
      organozinc reagents to aldehydes. The asymmetric ethylation, methylation,
      arylation, and alkynylation of aldehydes achieved enantioselectivity of up to
      98.4%, 94.1%, 99.0%, and 84.6% ee, respectively, in the presence of a catalytic
      amount of chiral N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol. Our results
      demonstrated further that the four-membered heterocycle-based backbone was a good
      potential chiral unit for the catalytic asymmetric induction reaction, and the
      hindrance of the bulky ferrocenyl group, compared to a phenyl group, played an
      important role in the enantioselectivities. A possible transition for the
      catalytic asymmetric addition has been proposed on the basis of the crystal
      structure of the chiral ligand 3b including two HOAc molecules and previous
      studies.

PMID- 18062702
TI  - Photochemical generation of oligodeoxynucleotide containing a C4'-oxidized abasic
      site and its efficient amine modification: dependence on structure and
      microenvironment.
AB  - Bleomycin-induced oxidative DNA damage under limited oxygen conditions results in
      the formation of the C4'-oxidized abasic site (1). We synthesized the
      oligodeoxynucleotides (ODN) 5, which contains 4'-o-nitrobenzyloxythymidine (3),
      and 6, which contains 2-nitrobenzyloxy-4'-methoxy-2'-deoxy-d-ribofuranoside (4),
      as the caged precursors of 7, an ODN containing 1, to study its reactivity with
      amines. Photoirradiation of the single- and double-stranded 5 led to the
      formation of 7. Uncaging of the duplex was faster and the yield of 7 was higher
      with the double-stranded than with the single-stranded ODN. It was suggested that
      a low dielectric environment of the o-nitrobenzyloxy group in the minor groove of
      the duplex might accelerate the uncaging rate. Similarly, 6 and its duplex
      yielded 7 by photoirradiation. However, the yields of 7 were lower than those of
      5, and duplex formation slowed the uncaging rate. Reaction of the obtained 7 with
      an amine resulted in the formation of the lactam 2b in good yield in both single-
      and double-stranded forms, showing that amine modification of biomolecules by an
      ODN containing 1 is possible under physiologic conditions.

PMID- 18062703
TI  - Preparation and X-ray structures of 3-[Bis(trifluoroacetoxy)iodo]benzoic acid and
      3-[hydroxy(tosyloxy)iodo]benzoic acid: new recyclable hypervalent iodine
      reagents.
AB  - Preparation, structural characterization, and reactivity of 3
      [bis(trifluoroacetoxy)iodo]benzoic acid and 3-[hydroxy(tosyloxy)iodo]benzoic
      acid, new recyclable iodine(III) reagents derived from 3-iodosylbenzoic acid, are
      described. The reduced form of these reagents, 3-iodobenzoic acid, can be easily
      recovered from the reaction mixtures using ion-exchange resin or basic aqueous
      workup followed by acidification with HCl.

PMID- 18062704
TI  - Nonthermal microwave effects revisited: on the importance of internal temperature
      monitoring and agitation in microwave chemistry.
AB  - The concept of nonthermal microwave effects has received considerable attention
      in recent years and is the subject of intense debate in the scientific community.
      Nonthermal microwave effects have been postulated to result from a direct
      stabilizing interaction of the electric field with specific (polar) molecules in
      the reaction medium that is not related to a macroscopic temperature effect. In
      order to probe the existence of nonthermal microwave effects, four synthetic
      transformations (Diels-Alder cycloaddition, alkylation of triphenylphosphine and
      1,2,4-triazole, direct amide bond formation) were reevaluated under both
      microwave dielectric heating and conventional thermal heating. In all four cases,
      previous studies have claimed the existence of nonthermal microwave effects in
      these reactions. Experimentally, significant differences in conversion and/or
      product distribution comparing the conventionally and microwave-heated
      experiments performed at the same measured reaction temperature were found. The
      current reevaluation of these reactions was performed in a dedicated reactor
      setup that allowed accurate internal reaction temperature measurements using a
      multiple fiber-optic probe system. Using this technology, the importance of
      efficient stirring and internal temperature measurement in microwave-heated
      reactions was made evident. Inefficient agitation leads to temperature gradients
      within the reaction mixture due to field inhomogeneities in the microwave cavity.
      Using external infrared temperature sensors in some cases results in significant
      inaccuracies in the temperature measurement. Applying the fiber-optic probe
      temperature monitoring device, a critical reevaluation of all four reactions has
      provided no evidence for the existence of nonthermal microwave effects. Ensuring
      efficient agitation of the reaction mixture via magnetic stirring, no significant
      differences in terms of conversion and selectivity between experiments performed
      under microwave or oil bath conditions at the same internally measured reaction
      temperatures were experienced. The observed effects were purely thermal and not
      related to the microwave field.

PMID- 18062705
TI  - On-line gas-free electrodialytic eluent generator for capillary ion
      chromatography.
AB  - Both low- and high-pressure, gas-free, capillary-scale electrodialytic generators
      for eluents in ion chromatography are described. While the low-pressure devices
      rely on planar or tubular membranes, the high-pressure devices rely on ion
      exchange beads used both as one-way ionic gates and as ball-on-seat valves to
      provide sealing. The high-pressure device is easily implemented in the form of a
      commercial cross fitting and can withstand at least 1400 psi. By design these
      devices do not produce gas in the eluent channel; hence, it is not necessary to
      remove gas afterward. With appropriate electrolytes and electrode polarities,
      such devices can produce either acid or base or salt. In regard to ionic
      transport, the behavior of these devices fully corresponds to that of a
      semiconductor diode. To our knowledge, this is the first time such complete
      equivalence of ion transport through ion-exchange media and with the more
      familiar example of electron transport through a semiconductor diode under both
      forward- and reverse-biased conditions have been demonstrated. Reverse bias can
      be applied to minimize/prevent Donnan-forbidden leakage or ion exchange. Even
      with 4 M KOH in the electrode compartments and 4 microL/min water flowing through
      the eluent channel, with a reverse bias of -12 V, the leakage KOH concentration
      is <30 microM, whereas the KOH concentration with zero voltage applied, herein
      after termed open circuit penetration (OCP), is 1600 microM. It is suggested that
      this OCP occurs not as much through Donnan-forbidden leakage but via ion
      exchange. Chromatograms and reproducibility data are presented for both isocratic
      and gradient chromatography, using ion-exchange, latex-modified, open tubular and
      packed monolithic columns.

PMID- 18062706
TI  - Initial synthesis and characterization of an alpha7 nicotinic receptor cellular
      membrane affinity chromatography column: effect of receptor subtype and cell
      type.
AB  - In this study, cellular membrane fragments from SH-EP1-pCEP4-halpha7 and alpha7
      HEK-293 cell lines were used to synthesize cellular membrane affinity
      chromatography (CMAC) columns containing functional alpha7 nicotinic
      acetylcholine receptors, CMAC(alpha7 nAChR) columns. The synthesis of stable
      columns required the addition of cholesterol to the 2% cholate
      solubilization/immobilization (s/i) buffer and to the mobile phase. In addition,
      when membranes from the SH-EP1 cell line were used, l-alpha-phosphatidylserine
      and l-alpha-phosphatidylethanolamine also had to be added to the s/i buffer. A
      CMAC(alpha4beta2 nAChR) column was prepared using membrane fragments from a SH
      EP1-pCEP4-halpha4beta2 cell line, and this process required the addition of l
      alpha-phosphatidylserine and l-alpha-phosphatidylethanolamine to the s/i buffer,
      but not cholesterol. The s/i buffers from the three columns were compared with
      the s/i buffer utilized in the preparation of a CMAC(alpha4beta2 nAChR) column
      prepared using an alpha4beta2 HEK-293 cell line, which required no additions to
      the 2% cholate s/i buffer. The data demonstrate that both cell type and receptor
      type affect the protocol required to produce a stable CMAC column and that, at
      the current time, the development of an optimum immobilization protocol is an
      empirical process. The results are also consistent with the observation that the
      alpha7 nAChR is localized in lipid rafts in both of these cell lines and that the
      cholate detergent removed cholesterol from these microdomains.

PMID- 18062707
TI  - Binding of phosphatase inhibitor-2 to prolyl isomerase Pin1 modifies specificity
      for mitotic phosphoproteins.
AB  - Inhibitor-2 (I-2) is the most ancient protein that selectively recognizes type-1
      protein phosphatase and is phosphorylated by CDK1-cyclinB during mitosis at Thr72
      in a conserved PXTP site. Pin1 is a peptide prolyl cis/trans isomerase conserved
      among eukaryotes that specifically reacts with proteins phosphorylated at Ser/Thr
      Pro sites. We tested phospho-T72-I-2 as a substrate for Pin1 and discovered that
      unphosphorylated I-2 bound Pin1 with micromolar affinity and phosphorylation of
      the PXTP site or truncation of I-2 reduced binding 10-fold. Ectopic Pin1
      coprecipitated endogenous I-2 and ectopic I-2 coprecipitated endogenous Pin1, but
      only in the absence of detergents, which may account for the interaction not
      being detected previously. Endogenous I-2 and Pin1 colocalized in HeLa cells and
      showed nuclear-cytoplasmic redistribution in response to cell density, suggestive
      of their association in living cells. Recombinant Pin1 binding to different
      phosphoproteins in mitotic cell extracts was modulated by I-2, and binding to
      individual mitotic phosphoproteins was increased, decreased or unaffected by I-2,
      showing that I-2 allosterically modifies Pin1 specificity. This was confirmed by
      mutation of Ser16 to Ala in the Pin1 WW domain that eliminated I-2 binding and
      abrogated I-2 effects on Pin1 binding to different phosphoproteins. A S16E
      mutation to mimic Pin1 phosphorylation restored binding to both I-2 and phospho
      T72-I-2, indicating that phosphorylation of both proteins governs their
      interaction. The results reveal a novel function for I-2, and suggest
      phosphorylation-dependent regulation of Pin1 specificity during entry and exit of
      mitosis, in other phases of the cell cycle, and in multiple cell signaling
      processes.

PMID- 18062708
TI  - Formation of ordered self-assembled monolayers by adsorption of octylthiocyanates
      on Au(111).
AB  - Self-assembled monolayers (SAMs) were formed by the spontaneous adsorption of
      octythiocyanate (OTC) on Au(111) using both solution and ambient-pressure vapor
      deposition methods at room temperature and 50 degrees C. The surface structures
      and adsorption characteristics of the OTC SAMs on Au(111) were characterized by
      scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS).
      The STM observation showed that OTC SAMs formed in solution at room temperature
      have unique surface structures including the formation of ordered and disordered
      domains, vacancy islands, and structural defects. Moreover, we revealed for the
      first time that the adsorption of OTC on Au(111) in solution at 50 degrees C led
      to the formation of SAMs containing small ordered domains, whereas the SAMs
      formed by vapor deposition at 50 degrees C had long-range ordered domains, which
      can be described as (radical3 x 2 radical19)R5 degrees structures. XPS
      measurements of the peaks in the S 2p and N 1s regions for the OTC SAMs showed
      that vapor deposition is the more effective method as compared to solution
      deposition for obtaining high-quality SAMs by adsorption of OTC on gold. The
      results obtained will be very useful in understanding the SAM formation of
      organic thiocyanates on gold surfaces.

PMID- 18062709
TI  - Quantifying growth of symmetric and asymmetric lipid bilayer domains.
AB  - Here, we examine by atomic force microscopy (AFM) the kinetics and morphology of
      lipid domain growth during lipid phase separation by rapid thermal cooling of
      fully mixed two-component supported lipid bilayers. At the undercooled
      temperatures chosen, symmetric 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)
      rich domains favored slower reaction-limited growth whereas asymmetric
      galactosylceramide (GalCer)-rich domains favored faster diffusion-limited growth,
      indicated by shape factors and kinetic exponents. Because kinetically limited
      conditions could be accessed, we were able to estimate the activation energy
      barrier (approximately 16kT) and lateral diffusion coefficient (approximately
      0.20 microm2/s) of lipid molecular addition to a growing domain. We discuss these
      results with respect to transition states, obstructed diffusion, and the
      necessity for coordinating growth in both leaflets in a symmetric lipid domain.

PMID- 18062711
TI  - Electrostatic interactions of colloidal particles in nonpolar solvents: role of
      surface chemistry and charge control agents.
AB  - We study the electrostatic and hydrodynamic interactions of colloidal particles
      in nonpolar solvents. Using blinking optical tweezers, we can extract the
      screening length, kappa-1, the effective surface potential, |ezeta*|, and the
      hydrodynamic radius, ah, in a single measurement. We apply this technique to
      suspensions of polystyrene and poly(methyl methacrylate) particles in hexadecane
      with soluble charge control agents, aerosol sodium di-2-ethylhexylsulfosuccinate
      (AOT) and polyisobutylene succinimide (OLOA-1200). We find that the electrostatic
      interactions of these particles depend sensitively on surface composition as well
      as on the concentration and chemistry of the charge control agent.

PMID- 18062710
TI  - Reverse engineering of an affinity-switchable molecular interaction characterized
      by atomic force microscopy single-molecule force spectroscopy.
AB  - Tunable and switchable interaction between molecules is a key for regulation and
      control of cellular processes. The translation of the underlying physicochemical
      principles to synthetic and switchable functional entities and molecules that can
      mimic the corresponding molecular functions is called reverse molecular
      engineering. We quantitatively investigated autoinducer-regulated DNA-protein
      interaction in bacterial gene regulation processes with single atomic force
      microscopy (AFM) molecule force spectroscopy in vitro, and developed an
      artificial bistable molecular host-guest system that can be controlled and
      regulated by external signals (UV light exposure and thermal energy). The
      intermolecular binding functionality (affinity) and its reproducible and
      reversible switching has been proven by AFM force spectroscopy at the single
      molecule level. This affinity-tunable optomechanical switch will allow novel
      applications with respect to molecular manipulation, nanoscale rewritable
      molecular memories, and/or artificial ion channels, which will serve for the
      controlled transport and release of ions and neutral compounds in the future.

PMID- 18062712
TI  - Selective adsorption of poly(ethylene oxide) onto a charged surface mediated by
      alkali metal ions.
AB  - Using a surface force balance, we have measured normal and shear interactions
      between mica surfaces across pure water and across 0.1 M aqueous solutions of
      LiNO3, NaNO3, KNO3, and CsNO3, both prior to adding polymer and following
      addition of 1.5 x 10(-4) w/w poly(ethylene oxide) (PEO, Mw = 170 kD) and
      overnight incubation. Our results reveal that while the PEO adsorbs strongly from
      the KNO3 and CsNO3 solutions, unexpectedly it does not adsorb at all from the
      LiNO3 and NaNO3 salt solutions. We attribute this to the different nature of the
      hydration layers about the alkali metal ions: these favor liganding to the
      negatively charged mica surface of the etheric -O- group on the ethylene oxide
      monomer for the case of the more weakly hydrated K+ and Cs+, but not for the case
      of Na+ or Li+ with their more strongly bound water. A simple model relating the
      electrostatic energy changes occurring upon such liganding to the experimentally
      measured hydration energies of the different alkali metal ions supports this
      attribution.

PMID- 18062713
TI  - Fabrication and characterization of patterned single-crystal silicon nanolines.
AB  - This letter demonstrates a method for fabricating single-crystal Si nanolines,
      with rectangular cross sections and nearly atomically flat sidewalls. The high
      quality of these nanolines leads to superb mechanical properties, with the strain
      to fracture measured by nanoindentation tests exceeding 8.5% for lines of 74 nm
      width. A large displacement burst before fracture was observed, which is
      attributed to a buckling mechanism. Numerical simulations show that the critical
      load for buckling depends on the friction at the contact surface.

PMID- 18062714
TI  - Targeted photothermal lysis of the pathogenic bacteria, Pseudomonas aeruginosa,
      with gold nanorods.
AB  - Increases in the prevalence of antibiotic resistant bacteria require new
      approaches for the treatment of infectious bacterial pathogens. It is now clear
      that a nanotechnology-driven approach using nanoparticles to selectively target
      and destroy pathogenic bacteria can be successfully implemented. We have explored
      this approach by using gold nanorods that have been covalently linked to primary
      antibodies to selectively destroy the pathogenic Gram-negative bacterium,
      Pseudomonas aeruginosa. We find that, following nanorod attachment to the
      bacterial cell surface, exposure to near-infrared radiation results in a
      significant reduction in bacterial cell viability.

PMID- 18062716
TI  - Guidelines for the management of lyme disease : the controversy and the quandary.

PMID- 18062717
TI  - Induction therapy in renal transplantation : an overview of current developments.
AB  - An overview of the past 10 years of clinical renal transplantation would include
      progress in the development of new induction protocols (non-depleting versus
      depleting monoclonal and polyclonal antibodies, plasmapheresis and intravenous
      immunoglobulins) designed to reduce the incidence and severity of rejection and
      adverse effects as well as improve long-term graft and patient survival. These
      modalities have been introduced primarily to reduce the incidence of acute
      rejection episodes leading to early graft loss, decrease the need for higher
      toxic doses of maintenance immunosuppressive drugs, such as calcineurin
      inhibitors, and possibly aid in the pursuit of the goal of achieving
      immunological tolerance and the avoidance of all long-term immunosuppressive
      therapy. What has resulted during the past 20 years as the use of induction
      agents has become more popular is the concurrent improvement in detection and
      treatment of acute and chronic infectious (primarily viral), and opportunistic
      and quasi-malignant disease accompanying the use of these agents and, therefore,
      their increase in popularity. However, the overall cost of therapy and the long
      term results of protocols in which these agents have been used have not resulted
      in a definitive benefit thus far, because of the lack of sufficient numbers of
      defined randomised, long-term studies and the continuing introduction of newer
      protocols based on even more recent advances. The specific agents used for
      induction therapy to date, and the rationale for their introduction and
      mechanisms of action are discussed in this review.

PMID- 18062718
TI  - The role of sulodexide in the treatment of diabetic nephropathy.
AB  - Diabetic nephropathy is an important cause of morbidity and mortality in patients
      with either type 1 or type 2 diabetes mellitus. The pathogenesis and natural
      history of diabetic nephropathy, characterised by a progressive decline in
      glomerular function, were initially described in patients with type 1 diabetes.
      Reports that describe the glomerulopathy and progression of renal disease in
      patients with type 2 diabetes suggest that the disease process is similar to that
      observed in patients with type 1 diabetes with diabetic nephropathy. An emerging
      body of evidence supports the notion that glomerular capillary wall and mesangial
      alterations in diabetic nephropathy involve pathobiochemical alterations of
      glycoproteins in these structures. Evidence in experimental animals rendered
      diabetic, reveal that the administration of heparin and other anionic
      glycoproteins can effectively prevent the biochemical alterations that promote
      albuminuria. Clinical reports of the use of sulodexide, a preparation of low
      molecular weight glycosaminoglycan polysaccharides, have shown that proteinuria
      is significantly diminished in patients with diabetic nephropathy, even when
      these patients are receiving either an ACE inhibitor or angiotensin receptor
      antagonist.

PMID- 18062719
TI  - Treatment of lysosomal storage disorders : progress with enzyme replacement
      therapy.
AB  - Enzyme replacement therapy (ERT) as treatment for lysosomal storage diseases
      (LSDs) was suggested as long ago as 1966 by De Duve and Wattiaux. However, it
      took >35 years to demonstrate the safety and effectiveness of ERT for type 1
      Gaucher's disease. An important breakthrough was certainly the enactment of
      legislation in the US, designed to encourage commercialisation of products
      developed in academic institutions for pharmaceutical companies to invest in
      treatments for rare diseases. The principles elaborated in the development of the
      treatment of Gaucher's disease were subsequently applied to the development of
      ERT of other LSDs. The safety and effectiveness of ERT for Fabry's disease,
      mucopolysaccharidoses (MPS) I, MPS II and MPS VI, as well as for Pompe's disease
      have been demonstrated in well designed clinical trials, and the treatments are
      now commercially available throughout the world. Several questions remain to be
      answered. The long-term effectiveness of most of the treatments has not yet been
      established. What is reversible by ERT and what may not be reversible but is
      preventable, is not yet clear. The pathology in some tissues, such as the brain,
      is inaccessible to ERT, indicating that some manifestations of the LSD will not
      respond to the treatment. The extent of this problem is still unclear. The cost
      of ERT is very high, creating problems for third-party payers, which has strained
      reimbursement schemes based on the demonstration of acceptable cost
      effectiveness. ERT of LSDs represents the most important advance in the treatment
      of this class of diseases. The information that is currently being collected as
      part of large-scale observational studies will help to establish the full
      potential of the treatment.

PMID- 18062720
TI  - Histamine and leukotriene receptor antagonism in the treatment of allergic
      rhinitis: an update.
AB  - Allergic rhinitis represents a global health burden. The disease can seriously
      affect quality of life and is associated with multiple co-morbidities. Histamine
      and leukotrienes are important pro-inflammatory mediators in nasal allergic
      inflammation. Their actions on target cells are mediated through specific
      receptors and, consequently, molecules that block the binding of histamine and
      leukotrienes to their receptors have been important areas of pharmacological
      research. The published literature of the pathophysiology of histamine and
      leukotrienes, and the effects of histamine H(1)-receptor antagonists (H(1)
      antihistamines) and leukotriene antagonists in monotherapy or in combination
      therapy in the treatment of allergic rhinitis was reviewed. The presented results
      are based on the best available evidence. The efficacy of H(1) antihistamines and
      leukotriene antagonists (montelukast in particular) in allergic rhinitis has been
      established in numerous randomised placebo-controlled trials. Results from meta
      analyses indicate that H(1) antihistamines and leukotriene antagonists are
      equally effective in improving symptoms of allergic rhinitis and quality of life,
      but that both drugs are less effective than intranasal corticosteroids. Data on
      the combination of H(1) antihistamines and leukotriene antagonists in allergic
      rhinitis are limited. The available evidence shows that a combined mediator
      inhibition has additional benefits over the use of each agent alone, but is still
      inferior to intranasal corticosteroids. More well designed studies are needed to
      fully understand the benefits of a concomitant use of these agents.

PMID- 18062723
TI  - Trastuzumab : in HER2 and hormone receptor co-positive metastatic breast cancer.
AB  - Trastuzumab is a humanised IgG1 monoclonal antibody, which selectively binds to
      the human epidermal growth factor receptor 2 (HER2), inhibiting cell
      proliferation and survival in HER2-dependent tumours. In a randomised phase III
      trial in postmenopausal women with HER2 and hormone receptor (HR) co-positive
      metastatic breast cancer, median progression-free survival (primary endpoint) was
      significantly longer in patients receiving intravenous trastuzumab plus oral
      anastrozole than in those receiving anastrozole alone. Overall response rate and
      clinical benefit rate were also significantly higher, and median time to disease
      progression was significantly longer with trastuzumab plus anastrozole versus
      anastrozole alone. There were no reports of new or unexpected adverse events with
      trastuzumab plus anastrozole combination therapy in the randomised phase III
      trial. In a noncomparative phase II study of trastuzumab plus letrozole in
      postmenopausal women with HER2 and HR co-positive metastatic breast cancer, the
      majority of adverse events were mild or moderate in severity.

PMID- 18062722
TI  - Rosiglitazone : a review of its use in type 2 diabetes mellitus.
AB  - Rosiglitazone (Avandia) is an antihyperglycaemic agent of the thiazolidinedione
      class that improves glycaemic control (as indicated by glycosylated haemoglobin
      [HbA1c] and fasting plasma glucose [FPG] levels) primarily by increasing hepatic
      and peripheral insulin sensitivity, and in addition may help to preserve
      pancreatic beta-cell function. In general, rosiglitazone as monotherapy or in
      combination with other antihyperglycaemic agents, including metformin or
      sulfonylureas, improves glycaemic control in adults with type 2 diabetes mellitus
      and may slow disease progression associated with pancreatic beta-cell function
      decline. Rosiglitazone is generally well tolerated; however, additional long-term
      and comparative studies are required to further evaluate the effects of
      rosiglitazone on bone and the potential cardiovascular risk of the drug,
      including the risk relative to pioglitazone. Thus, in light of recent
      cardiovascular safety concerns and the need for further long-term data to clarify
      the potential risk of rosiglitazone in this regard, it would be prudent to use
      rosiglitazone in the treatment of type 2 diabetes on a case-by-case basis, taking
      into account individual patient cardiovascular risk factors.

PMID- 18062724
TI  - Darunavir: in the treatment of HIV-1 infection.
AB  - Darunavir (TMC114) is a nonpeptidic peptidomimetic HIV protease inhibitor (PI),
      with a high binding affinity and a close fit within the substrate envelope.
      Darunavir shows potent in vitro activity against a broad range of clinical
      isolates of HIV type 1 (HIV-1), including those with decreased susceptibility to
      most available PIs. The bioavailability of oral darunavir is increased when it is
      coadministered in combination with low-dose (100mg) ritonavir. In the POWER 1 and
      POWER 2 trials, two 144-week randomised phase IIb trails, a reduction in plasma
      HIV-1 RNA levels of > or = 1 log10 copies/mL (primary endpoint) occurred in 77%
      and 62% of treatment-experienced recipients of darunavir plus ritonavir
      (darunavir/ritonavir) 600mg/100mg twice daily (in combination with an optimised
      background regimen) [vs 25% and 14% of control PI (CPI) recipients; p < 0.001] at
      week 24. Results are from primary analyses (n = 301 and 201). In a pooled
      subgroup analysis of data from the POWER 1 and 2 trials, reductions in HIV-1 RNA
      levels of > or = 1 log10 copies/mL were achieved in 61% of patients treated with
      darunavir/ritonavir 600mg/100mg twice daily verus 15% of CPI recipients (p <
      0.0001) at week 48. Darunavir/ritonavir 600mg/100mg was generally well tolerated
      in the POWER 1 and 2 trials, with a tolerability profile similar to that of
      comparator CPIs.

PMID- 18062721
TI  - Management of epilepsy during pregnancy.
AB  - Managing epilepsy during pregnancy is to balance the maternal and fetal risks
      associated with uncontrolled seizures against the potential teratogenic effects
      of antiepileptic drugs (AEDs). A rational approach requires knowledge of such
      risks as well as an understanding of the effects of pregnancy on seizure control
      and of gestational effects on AED disposition. Uncontrolled tonic-clonic seizures
      are potentially hazardous to the mother and, although strict evidence is lacking,
      are generally also assumed to be more harmful to the fetus than are AEDs.
      However, infants who have been exposed to AEDs in utero run an increased risk of
      congenital malformations: approximately twice the rate reported in the general
      population. Earlier literature has largely failed to demonstrate differences in
      birth defect rates with different treatment regimens, which can be ascribed
      mainly to insufficient sample sizes. More recent data have indicated higher
      malformation rates with exposure to valproic acid compared with some other major
      AEDs. The teratogenic effects of valproic acid appear to be dose dependent, with
      higher risks at dosage levels >1000 mg/day. Polytherapy involving treatment with
      more than one AED also seems to be associated with an increased risk of birth
      defects compared with monotherapy. Recently, a few small-scale studies have
      investigated the possibility that exposure to AEDs in utero may adversely affect
      the postnatal cognitive development of the offspring. Some of these studies have
      suggested that valproic acid poses a higher risk compared with other AEDs in this
      respect. These signals are important, but must be interpreted with caution
      because of the methodological shortcomings of the studies and because adequately
      powered prospective studies are necessary to draw firm conclusions. More
      reassuring findings have emerged regarding the obstetric outcome of pregnancy and
      the risk of worsening of epilepsy during pregnancy. In particular, it seems that
      the risk of obstetric complications is not significantly increased. Furthermore,
      most of the women with epilepsy have no change in their seizure frequency during
      pregnancy. The disposition of many AEDs may change during pregnancy, reflected in
      declining plasma drug concentrations. This seems to be most pronounced for
      lamotrigine and possibly also for oxcarbazepine, and can result in break-through
      seizures. The common treatment strategy has been to use the appropriate AED for
      the woman's seizure disorder as monotherapy in the lowest effective dosage
      throughout pregnancy, the objective being to use AEDs in such a way that
      generalised tonic-clonic seizures are avoided but with minimised risks to the
      fetus, the newborn and the breast-fed infant. Valproic acid should be avoided if
      possible. Any major change in the treatment of a woman with epilepsy should
      ideally be completed before conception. Regular monitoring of drug concentrations
      is recommended during pregnancy, in particular for lamotrigine and oxcarbazepine.

PMID- 18062725
TI  - Darunavir in the treatment of HIV-1 infection: a viewpoint by Mark Holodniy.

PMID- 18062726
TI  - Darunavir in the treatment of HIV-1 infection: a viewpoint by Renslow Sherer.

PMID- 18062727
TI  - Increased sensitivity and variability of phytotoxicity responses in Arctic soils
      to a reference toxicant, boric acid.
AB  - Industrial and human activities in the Arctic regions may pose a risk to
      terrestrial Arctic ecosystem functions. One of the most common terrestrial
      toxicological end points, primary productivity, typically is assessed using a
      plant phytotoxicity test. Because of cryoturbation, a soil mixing process common
      in polar regions, we hypothesized that phytotoxicity test results in Arctic soils
      would be highly variable compared to other terrestrial ecosystems. The
      variability associated with phytotoxicity tests was evaluated using Environment
      Canada's standardized plant toxicity test in three cryoturbated soils from
      Canada's Arctic exposed to a reference toxicant, boric acid. Northern wheatgrass
      (Elymus lanceolatus) not only was more sensitive to toxicants in Arctic soils,
      its response to toxicants was more variable compared to that in temperate soils.
      The phytotoxicity of boric acid in cryosols was much greater than commonly
      reported in other soils, with a boric acid concentration of less than 150
      microg/g soil needed to inhibit root and shoot growth by 20%. Large variability
      also was found in the phytotoxicity test results, with coefficients of variation
      for 10 samples ranging from 160 to 79%. The increased toxicity of boric acid in
      cryosols and variability in test response was not explained by soil properties.
      Based on our admittedly limited data set of three different Arctic soils, we
      recommend that more than 30 samples be taken from each control and potentially
      impacted area to accurately assess contaminant effects at sites in northern
      Canada. Such intensive sampling will insure that false-negative results for
      toxicant impacts in Arctic soils are minimized.

PMID- 18062728
TI  - Effect on drug utilization and expenditures of a cost-share change from copayment
      to coinsurance.
AB  - BACKGROUND: While increases in prescription drug spending have moderated in
      recent years, drug spending is still a concern among managed care organizations
      and health plan administrators. In order to minimize cost increases from year to
      year, many health care plans have shifted more of the cost of medications to the
      member-consumer. Coinsurance, a benefit design in which the patient pays a
      percentage of the cost of the medication, is garnering more attention as a type
      of cost-sharing that differs from the traditional copayment model. OBJECTIVE: To
      estimate the impact on medication expenditures and utilization of a pharmacy
      benefit design change from 3-tier copayment to coinsurance. METHODS: Drug
      expenditures and utilization of beneficiaries aged >or =18 years and continuously
      enrolled in 2 privately insured groups were compared before and after a benefit
      design change in 1 of the groups. For the 12 months before the benefit design
      change, both groups had a 3-tier, fixed-dollar copayment structure with identical
      cost-sharing per 30-day supply: $10 tier-1 copayment for generic drugs, $25 tier
      2 copayment for preferred brand drugs, and $40 tier-3 copayment for non-preferred
      brand drugs. On September 1, 2005, a 4-tier coinsurance benefit design (25% for
      all tiers except tier-3 [non-preferred] drugs at 50%, with minimum and maximum
      patient out-of-pocket [OOP] cost applied to each tier) was implemented in the
      intervention group (N = 46,311). The 3-tier copayment design was maintained in
      the comparison group (N = 7,916). A difference-in-difference analysis was used to
      estimate the effect of the benefit design change on expenditures and utilization,
      overall (for all prescription drugs), and for 3 classes of essential medications:
      antihypertensives, antidepressants, and statins. Analyses measured changes in
      outcomes from 6 months pre-change (October 1, 2004, through March 31, 2005)
      through 6 months post-change (October 1, 2005, through March 31, 2006). In the
      overall (all drug) analyses, per member per month (PMPM) outcome measures were
      total pharmacy claims and cost, beneficiary (patient OOP) cost, and employer
      (plan sponsor) cost. Analyses of the 3 essential drug classes were limited to
      members with at least 1 claim in the drug class in both the pre-change and post
      change periods (N = 11,917, intervention group; 1,792, comparison group), and
      assessed per patient per month (PPPM) days supply, beneficiary cost, employer
      cost, and total cost. RESULTS: Beneficiaries in the intervention group paid 31.8%
      of total pharmacy benefit cost at the point of care versus 31.5% in the
      comparison group in the post-change period. The increases in beneficiary cost
      from the pre-change period to the post-change period were not significantly
      different for the intervention (7.5%) and comparison (3.0%) groups (P = 0.983).
      From the pre-change period to the post-change period, total spending per member
      increased $4.57 PMPM (6.3%), from $72.29 to $76.87 in the intervention group
      versus a $5.87 PMPM increase (9.5%), from $61.54 to $67.41, in the comparison
      group, a relative difference of $1.30 PMPM (P = 0.013). The increases in
      utilization from the pre-change period to the post-change period were not
      significantly different in the intervention group (2.4%) versus the comparison
      group (4.6%, P = 0.189). Utilization per patient in the 3 essential drug classes
      increased 4.1% (1.59 days PPPM) in the intervention group versus 9.0% (3.23 days
      PPPM) in the comparison group (P = 0.004). Total expenditures in the 3 classes
      for the intervention and comparison groups increased 8.2% ($5.07 PPPM) and 13.3%
      ($7.80 PPPM), respectively, a difference of $2.73 PPPM (P = 0.003). Beneficiary
      cost for all 3 drug classes increased $2.20 PPPM (9.2%) in the intervention group
      versus $2.12 PPPM (9.1%) in the comparison group (P = 0.032). The increases in
      employer cost for the 3 essential drug classes in the intervention group (7.5%,
      $2.86 PPPM) and comparison group (16.1%, $5.67 PPPM) did not significantly differ
      (P = 0.057). CONCLUSIONS: A pharmacy benefit design change from tiered copayment
      to tiered coinsurance, without a significant increase in beneficiary OOP costs,
      was associated with a lower rate of increase in total pharmacy benefit cost and
      no significant reduction in utilization. For utilizers in 3 essential drug
      classes, drug utilization and total spending increased in the coinsurance group
      but at a lower rate of increase compared with the copayment group. The
      coinsurance design provides another approach for controlling prescription
      utilization and spending for certain medication classes.

PMID- 18062729
TI  - Economic burden of atopic manifestations in patients with atopic dermatitis-
      analysis of administrative claims.
AB  - BACKGROUND: Atopic dermatitis (AD) has been associated with atopic manifestations
      (AMs), such as food allergies, asthma, allergic rhinitis, and allergic
      conjunctivitis. OBJECTIVES: To (1) compare the risk of developing AMs in patients
      with AD versus those without AD, (2) estimate the incremental costs attributable
      to AMs in patients with AD, and (3) examine the factors associated with
      incremental costs. METHODS: In this retrospective cohort study, the authors used
      MarketScan research databases containing medical and pharmacy claims with dates
      of service from January 1, 1999, to December 31, 2004. Patients were considered
      to have AD if they had at least 1 medical claim with a primary or secondary
      diagnosis of AD (International Classification of Diseases, Ninth Revision,
      Clinical Modification [ICD-9-CM] codes 691.8x) or contact dermatitis or other
      eczema of unspecified cause (ICD-9-CM codes 692.9x). To create comparable study
      cohorts, patients with AD were matched with non-AD patients using propensity
      scores that represented the likelihood of developing AD as predicted by logistic
      regression. After propensity score matching, the AD and non-AD cohorts did not
      statistically differ with respect to age, gender, geographic region, type of
      health insurance, Charlson Comorbidity Index, or baseline measures of medical and
      prescription drug utilization. The relative risks of developing AMs in the AD and
      non-AD cohorts were estimated using competing risk-survival analysis. AM was
      defined by ICD-9-CM codes for asthma (493.xx), allergic rhinitis (477.xx),
      allergic conjunctivitis (372.05 or 372.14), and food allergy (693.1x, 692.5x,
      995.60). The annual incremental cost attributable to AMs in these AD patients was
      calculated from medical claims with AM and AD diagnosis codes and from pharmacy
      claims for prescription drugs used to treat asthma, allergic rhinitis, allergic
      conjunctivitis, or food allergy, and 95% confidence intervals (CIs) were
      calculated using the bootstrap method. RESULTS: Patients with AD were
      significantly more likely to develop AMs than patients without AD (21.8% versus
      16.9%, adjusted relative risk [RR] = 1.33, 95% CI, 1.28-1.38). Among AD patients
      who developed AMs, allergic rhinitis was the most frequent manifestation (66.3%),
      followed by asthma (24.8%), allergic conjunctivitis (7.6%), and food allergy
      (1.8%). The incidence and adjusted RRs of developing AM for AD patients versus
      comparison patients were 5.3% versus 4.5% for asthma (RR = 1.20, 95% CI, 1.12
      1.29), 14.6% versus 11.2% for allergic rhinitis (RR = 1.35, 95% CI, 1.29-1.41),
      1.6% versus 1.1% for allergic conjunctivitis (RR = 1.50, 95% CI, 1.31-1.72), and
      0.3% versus 0.1% for food allergy (RR = 2.35, 95% CI, 1.66-3.32). The annual AD +
      AM treatment costs for patients with AD increased substantially after they
      developed AMs. The additional financial burden attributable to AMs was estimated
      to be $482 per year, an almost 1.5-fold increase compared with AD cost alone
      (from $338 before AM development to $820 afterward, P < 0.001), with
      approximately equal distribution of costs between medical services ($243) and
      prescription drugs ($239). The largest incremental costs were observed in asthma
      ($973), followed by allergic rhinitis ($341). CONCLUSIONS: Patients with AD are
      significantly more likely to develop AM compared with patients without AD. The
      total treatment costs for AD patients who developed AMs were nearly 2.5 times the
      total treatment costs for patients with AD alone.

PMID- 18062730
TI  - Medical costs and resource utilization for hemophilia patients with and without
      HIV or HCV infection.
AB  - BACKGROUND: Previous research has shown that hemophilia patients infected in the
      1980s with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV) from
      the blood supply have increased morbidity and mortality. Although the possibility
      of contracting HIV or HCV through contaminated blood products has been virtually
      eliminated in the United States, approximately one third of hemophiliacs between
      the ages of 21 and 60 years are HIV infected. OBJECTIVE: To determine the health
      care resource utilization of adult hemophilia patients with and without HIV and
      HCV infection in a commercially insured population in the United States. METHODS:
      This was a retrospective claims analysis of the PharMetrics Patient-Centric
      database over an approximately 7-year period from January 1997 to April 2004. The
      database represents about 43 million members in commercial health plans. Male
      patients continuously enrolled for at least 6 months and >18 years of age were
      included in the study; female patients were excluded since they were likely to
      have von Willebrand disease. Hemophilia patients were identified if they had at
      least 1 claim with a primary diagnosis of hemophilia (International
      Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code
      286.XX) and at least 1 claim for a hemophilia drug (identified by National Drug
      Code number and J codes: J7190-J7199, Q0187 or Q2022). Clotting factor inhibitor
      patients identified through the dispensation of an activated prothrombin complex
      concentrate or recombinant factor VIIa were excluded from the study. Virally
      infected patients were identified as those hemophilia patients with at least 1
      claim with a HIV diagnosis (ICD-9-CM codes 042.xx, 079.53) or HCV infection (ICD
      9-CM codes 070.41, 070.44, 070.51, 070.54). Four cohorts for analysis were
      established: hemophilia without HIV or HCV coinfection (H-only); hemophilia + HIV
      (H + HIV); hemophilia + HCV (H + HCV); and hemophilia + HIV + HCV (H + HIV +
      HCV). The index date was defined as the first day of enrollment. Follow-up lasted
      until the end of the patient's enrollment or the end of the study period. The
      main outcomes of the study were (1) annualized net costs paid by health plans
      (after subtracting member cost-share) associated with all pharmacy and medical
      claims and (2) office visit distribution overall and by physician specialty
      during the study period. RESULTS: A total of 166 patients were identified for the
      study--73 with H-only, 12 with H + HIV, 44 with H + HCV, and 37 with H + HIV +
      HCV. The mean (median) annualized total cost of care in 2004 dollars was $90,942
      ($63,613) for the H-only cohort versus $108,862 ($64,782, P = 0.512) for the H +
      HIV cohort; $104,404 ($66,489, P = 0.377) for the H+HCV cohort; and $144,462
      ($111,542, P = 0.005) for the H + HIV + HCV coinfected cohort. Clotting factor
      accounted for 78% - 86% of total health care costs for all 4 groups of patients.
      Compared with the H-only cohort ($2,136), the H + HIV, H + HCV, and H + HIV + HCV
      cohorts had significantly higher mean non-hemophilia prescription drug costs
      ($8,239 [P = 0.001]; $7,275 [P = 0.034]; and $12,360 [P < 0.001], respectively).
      The H + HIV + HCV cohort had significantly higher hospital inpatient costs than
      did the H-only cohort ($5,655 vs. $3,360, respectively, P = 0.015). Mean
      annualized outpatient costs were higher in the H + HIV + HCV cohort ($12,897, P <
      0.001) and H + HCV cohort ($7,233, P = 0.016) than in the H-only cohort ($7,216).
      Mean annualized total numbers of office visits were higher for the H + HCV
      (11.18, P = 0.003) and H + HIV + HCV (18.33, P < 0.001) cohorts than for the H
      only cohort (6.98). Compared with the H-only cohort, the H + HIV + HCV cohort had
      a greater mean annualized number of visits to infectious disease specialists
      (3.75 vs. 0.12, P < 0.001) and to gastroenterology specialists (1.22 vs. 0.09, P
      < 0.001). CONCLUSION: The presence of HIV and HCV coinfection in hemophiliacs is
      associated with 59% (95% confidence interval, 34.8%, 82.9%) greater annual health
      care costs compared with costs for hemophilia alone. Coinfection with HIV and HCV
      is associated with significantly greater component costs for clotting factor,
      prescription drugs, inpatient services, and outpatient services.

PMID- 18062731
TI  - Utilization, cost trends, and member cost-share for self-injectable multiple
      sclerosis drugs--pharmacy and medical benefit spending from 2004 through 2007.
AB  - BACKGROUND: In 1993, interferon beta-1b became the first of 4 self-injectable
      multiple sclerosis (MS) drugs to be approved by the U.S. Food and Drug
      Administration. Initially covered as a medical expense, self-injectable MS drugs
      are increasingly considered specialty pharmaceuticals and are often covered under
      the pharmacy benefit. Self-injectable MS drugs are expensive, costing
      approximately $2,000 per month per patient in 2007. OBJECTIVES: To (1) determine
      the trends for price and utilization of self-injectable MS drugs, (2) meld
      medical and pharmacy claims data to capture total health care spending on self
      injectable MS drugs, and (3) calculate the out-of-pocket cost-share for members
      with pharmacy benefits. METHODS: A pharmacy benefits manager with integrated
      medical claims for approximately 1.8 million commercial members, about 20% of its
      total of 9 million commercial members, analyzed self-injectable MS pharmacy
      claims for a 45-month period beginning in January 2004 and ending in September
      2007 and integrated medical and pharmacy claims for a 42-month period beginning
      in January 2004 and ending in June 2007. The 9 million members are beneficiaries
      of 10 Blue Cross Blue Shield (BCBS) health plans distributed throughout the
      United States, and the subset of 1.8 million members are enrolled in 1 BCBS
      health plan in the Northern Plains states. Self-injectable MS drugs were
      identified using Generic Product Identifier (GPI) codes for the National Drug
      Code (NDC) numbers on pharmacy claims. Mail order pharmacy claims with up to a 90
      day supply were counted as 3 claims, and community pharmacy claims dispensed with
      up to a 34-day supply were counted as 1 claim. Self-injectable MS drugs were
      identified from medical claims using Healthcare Common Procedure Coding System
      (HCPCS) codes: J1595 for glatiramer, J1830 for subcutaneous interferon beta-1b,
      Q3026 for subcutaneous interferon beta-1a, and Q3025 and J1825 for intramuscular
      interferon beta-1a. RESULTS: For the approximately 9 million members with data
      from pharmacy claims only, these 4 self-injectable MS drugs accounted for
      approximately 1.8% of total pharmacy benefit spending in 2004, 1.9% in 2005, 2.3%
      in 2006, and 2.4% in 2007. The mean average wholesale price (AWP) per member per
      month (PMPM) increased by 56.8%, from $1.11 PMPM in the first quarter of 2004 to
      $1.74 PMPM in the third quarter of 2007. Utilization was flat at about 82-83
      claims per 100,000 members per month during the 45-month measurement period. The
      average annual price increase per unit ranged from 8.9% for interferon beta-1a to
      13.3% per year for interferon beta-1b. Members paid a median out-of-pocket cost
      per pharmacy claim of $15 in 2004, $20 in 2005 and 2006, and $25 in the first 9
      months of 2007. For the 1.8 million members with both pharmacy and medical
      benefit claims, the medical benefit accounted for 2.5% of total spending on MS
      self-injectables in 2004, 2.0% in 2005 and 2006, and 1.2% in 2007. CONCLUSION:
      The percentage of all pharmacy expenditures that was attributable to self
      injectable MS drugs increased from 1.8% in 2004 to 2.5% in 2007. Nearly all of
      the increase in spending on self-injectable MS drugs over the nearly 4-year
      period was attributable to drug price increases because PMPM utilization was
      essentially unchanged. The median member cost-share was approximately 1% of the
      total cost of self-injectable MS drugs.

PMID- 18062732
TI  - Improving medication adherence: the role of the health care delivery system and
      health care providers.

PMID- 18062733
TI  - Atopic march to a dead end or does the theory really have legs?

PMID- 18062734
TI  - Changes and challenges: managing ADHD in a fast-paced world.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) impairs the lives of
      both children and adults. Undiagnosed and untreated, ADHD may have serious
      lifelong consequences. Research has identified diagnostic clues, neurotransmitter
      pathways, and psychiatric comorbidities related to ADHD, as well as effective
      pharmacologic, behavioral, and psychosocial interventions. Stimulant agents have
      been the foundation of ADHD therapy for more than 50 years. Availability of new
      extended-release (XR or ER) and longer-acting (LA) formulations and novel agents
      allows for wider and more individualized treatment choices. Side effects of
      stimulants are generally mild, short lived, and responsive to adjustments in
      dosage or timing. Outcomes in ADHD treatment can be improved with the use of
      clear treatment guidelines and tools to aid clinicians in implementing them
      efficiently and effectively. The Texas Children's Medication Algorithm Project
      (CMAP) provides a system of algorithm-driven treatment decisions that is evidence
      based and easy to implement. OBJECTIVE: To (1) review the psychological
      components of attention, the neurotransmitter pathways associated with ADHD, and
      the array of therapeutic options for ADHD, with an emphasis on the most recent
      introductions to the therapeutic armamentarium; (2) discuss the rare psychiatric
      and cardiovascular side effects associated with stimulants; (3) review abuse
      liability, comorbidities, and suggested approaches to these issues; and (4)
      review the development and use of CMAP and offer resources for its implementation
      in clinical practice. CONCLUSION: The pathophysiology of ADHD is linked to
      dysfunction of fronto-subcortical networks and dysregulation of dopaminergic,
      noradrenergic, and nicotinic neurotransmitter systems. An additive effect of
      multiple genes as well as environmental influences contributes to the clinical
      picture. Treatment with stimulants and nonstimulants has proven effective in
      different subgroups, with the effectiveness of specific agents most likely
      related to the primary neurotransmitter involved. Availability of XR, ER, LA, and
      transdermal stimulant formulations, as well as alternative nonstimulant agents,
      offers new options for the pharmacotherapy of ADHD. Major concerns associated
      with abuse liability of stimulants have been allayed by the availability of ER
      formulations, which have reduced reinforcing effects associated with short-acting
      preparations. Medication outcomes in ADHD can be enhanced by the use of evidence
      based algorithms such as CMAP. Keys to success are adequate initial assessment
      and diagnosis, the use of sustained-release products, sufficient dose titration,
      and the use of clinical rating scales with feedback from caregivers and teachers.
      Optimal treatment outcomes can be achieved by appropriate pharmacotherapy
      combined with psychosocial interventions.

PMID- 18062735
TI  - The changing landscape of type 2 diabetes: the role of incretin-based therapies
      in managed care outcomes.
AB  - BACKGROUND: The prevalence of diabetes is growing in the United States and, for
      many patients, blood glucose continues to be poorly managed. Significantly, more
      than half of people with type 2 diabetes mellitus (T2DM) have hemoglobin A1Cs
      greater than 7%. Several factors contribute to the failure to achieve treatment
      goals, including clinical inertia (the failure to initiate or advance therapy in
      a patient who is not at the evidence-based therapeutic goal) and failure to
      address all components of disease pathophysiology. Newer classes of
      antihyperglycemic agents, the incretin-based therapies, have the potential to
      improve goal achievement. OBJECTIVE: To review incretin physiology and the latest
      clinical data on glucagon-like peptide-1 (GLP-1) mimetics and dipeptidyl
      peptidase-IV (DPP-4) inhibitors and to use this as a foundation to discuss the
      practical issues of disease management, including clinical inertia, clinical
      recommendations, and evaluation of the best fit for incretin-based therapies in
      current treatment paradigms. SUMMARY: Clinical inertia is an important
      contributing factor to T2DM treatment failure and may be improved through more
      specific diagnosis, more complete patient education, and an emphasis on earlier
      and more aggressive therapy in goal-oriented fashion. Based largely on the
      underlying pathophysiology of T2DM, newer ACE/AACE guidelines have been developed
      to facilitate this more aggressive approach. The incretin-based therapies can
      favorably impact some underlying elements in T2DM pathophysiology, including
      glucagon hypersecretion, rapid gastric emptying, postprandial hyperglycemia, and,
      possibly, chronic -cell dysfunction. When incorporated early into a long-term,
      treat-to-target management plan, incretin-based therapies have the potential to
      reduce the prevalence of treatment failure in T2DM and may positively impact
      disease progression. CONCLUSIONS: Clinicians need to recognize and address the
      scope and impact of clinical inertia on T2DM patient outcomes. Better use of
      conventional treatment options and/or consideration of newer incretin-based
      therapies can contribute to improvements in patient health.

PMID- 18062736
TI  - Quest for timely detection and treatment of women with depression.
AB  - BACKGROUND: Women are at risk for a wide range of depressive and anxiety
      disorders and particularly for mood disorders associated with their menstrual
      cycle, with seasonality, and during the menopausal transition. OBJECTIVE: To
      review the presentation of depression, the importance of timely and effective
      treatment, and some of the research surrounding increased prevalence of
      depression in women, and the times and conditions--such as the perimenopausal
      transition, pregnancy, postpartum period, and comorbidities--of this increased
      risk in women. SUMMARY: Dynamic interactions of both biological and environmental
      factors contribute to the development of major depression. These include, but are
      not limited to, predisposing genetic influences, gender, environmental stressors,
      poor social support, childhood sexual abuse, other psychiatric illness, and
      trauma. Timely and effective treatment of each episode of depression to remission
      is critically important. Barriers to instituting collaborative care of depressive
      illness are numerous. The lack of adequate collaborative care along with the
      consequent failure to adequately diagnose and treat depression reflects some of
      the deficiencies in the current organization and delivery of health services.
      CONCLUSION: The prevalence of depression, its psychosocial and medical
      consequences, and the worsening course of depression without treatment highlight
      the public health importance of early detection and improved strategies for the
      treatment of depression in modern health care settings.

PMID- 18062737
TI  - Psychosocial and cultural contributions to depression in women: considerations
      for women midlife and beyond.
AB  - BACKGROUND: Women share a greater burden of mood disorders than men and have
      twice the prevalence rate of depression. OBJECTIVE: To highlight some of the
      psychosocial and cultural contributions to depression in women. SUMMARY: Multiple
      factors contribute directly or interact to precipitate the onset of depression.
      Genetics, stress life events, previous history of depression, and cognitive
      factors have been shown to be significant risk factors for future depression
      episodes. Life stressors contribute to the onset of depression in both men and
      women, but particular stressors affect the genders differently, with women
      identifying more closely with relationship issues, lack of adequate housing, and
      poverty. Women are also more frequently affected by physical and sexual abuse,
      which will significantly influence future episodes of depression. Depression does
      not discriminate on the basis of race. Women of all ethnic groups suffer from
      depression. However, research indicates that there may be differences in
      prevalence and treatment-seeking behavior in black Americans, Mexican Americans,
      and white Americans. CONCLUSION: Many factors contribute to the occurrence of
      depression. Some of these occurrences may be explained by the changing hormonal
      milieu, susceptibility after physical or sexual abuse, poverty, housing problems,
      or loss of a close friend. One of the explanations for the higher rate of
      depression in women is that women have a greater incidence of first depressive
      episodes, which often begin during adolescence or young adulthood.

PMID- 18062738
TI  - Identifying and managing depression in women.
AB  - BACKGROUND: Depression is a complex disease often occurring with comorbid mental
      health or medical illnesses. It is highly prevalent and treated most frequently
      by a primary care physician (PCP). Depression affects the total health status of
      the patients who have it, and depression patients with comorbidities generally
      experience worse outcomes. It is also one of the most costly chronic illnesses,
      as measured by absenteeism and reduced productivity at work, direct medical
      costs, and suicide-related costs. Despite its high prevalence and being a
      frequent illness encountered during clinic visits, depression presents many
      challenges for the PCP in diagnosing and managing the illness and in bringing a
      patient to full remission. But depression is a highly treatable disorder. With
      appropriate diagnosis and intervention, depression can be reversed and most
      patients return to normal functioning. OBJECTIVE: To provide an overview of a
      case study of a 24-month, managed care, depression care management program that
      incorporated a bilayered approach to optimize patient outcomes. SUMMARY: Patients
      being treated for depression by a PCP were assigned a care coach who provided
      educational and goal-setting training by telephone. Psychiatric medical directors
      were involved in overseeing the treatment plan and consulted with PCPs to
      optimize treatment plans. CONCLUSION: Initial outcomes of this program indicate
      that it was successful in improving patient care and also in reducing overall
      costs associated with a depressed population. Results included a reduction in the
      average Hamilton Depression Rating Scale from 10.4 to 5.6, a 56% reduction in
      hospital admissions for depression, and an 18% total reduction in health care
      costs per member per month.

PMID- 18062739
TI  - Managed care best practices: the road from diagnosis to recovery: access to
      appropriate care.
AB  - BACKGROUND: Depression is a painful, functionally impairing, and frequently
      recurring condition. A costly illness for employers, depression contributes to
      reduced functioning, decreased work productivity, and absenteeism. In addition,
      costs associated with comorbidities in people who have depression are higher when
      they are compared with the costs in people who do not have depression. In
      patients with either coronary or cerebral vascular disease, depression
      significantly increases the risk of cardiovascular morbidity and mortality.
      OBJECTIVE: To highlight some of the challenges faced by primary care providers
      when they deliver mental health services and to provide an overview of an
      integrated behavioral health and medical benefit plan implemented as one solution
      to improve overall depression outcomes and reduce associated depression costs.
      SUMMARY: Because of the high prevalence and significant impact of depression, the
      U.S. Preventive Services Task Force recommends screening adults for depression in
      clinical practices that have systems in place to ensure accurate diagnosis,
      effective treatment, and follow-up. However, depression appears to be only
      partially recognized and inadequately treated in primary care due somewhat to
      several challenges that primary care practitioners face when they manage a mental
      health diagnosis along with comorbid medical illnesses. CONCLUSION: Integrating
      the medical and behavioral health benefits in a health plan allows for depression
      screening and the opportunity to direct patients to seek treatment when needed.
      Preliminary results of this effort in one managed care plan show reduced use of
      hospital services, days gained at work, and improved adherence to antidepressant
      therapy. A different component of this plan design includes patient care coaching
      as well as support of primary care's efforts by providing expert telephone
      consultation about treatment plans and allowing billing for adequate time spent
      with depressed patients.

PMID- 18062740
TI  - Rural children's perceptions of child farm safety printed communication
      strategies.
AB  - INTRODUCTION: Child farm safety has been identified as a key public health
      concern in Australia. To date, communication strategies for child farm safety
      have primarily targeted rural based adults as custodians of children, and because
      the greatest proportion of deaths occur in pre-school children. However, emerging
      international literature acknowledges the importance of understanding the
      perceptions and practices of children and adolescents as active agents for
      identifying and preventing hazard risks and accidents. This qualitative
      exploratory study examined how rural students aged 7-12 years read farm safety
      messages in printed farm safety communication tools, developed predominantly by
      Farmsafe Australia and Farmsafe Queensland. The study also identifies students'
      ideas to improve communication tools. METHODS: Seventeen focus groups were
      conducted in rural-based schools in a number of commodity regions across
      Australia. There was an average of eight students in each of these focus groups.
      The sample included children aged between 7 and 12 years. Focus groups were
      generally split into two age cohorts: 7-9 years (seven focus groups) and 10-12
      years (eight focus groups). Two focus groups were conducted with students in a
      composite age range of 7-12 years, due to the small number of students in those
      schools. Semi-structured questioning was used to explore students' perceptions of
      child farm safety printed communication tools, predominantly developed by
      Farmsafe Australia. The tools used for discussion were: a poster on the provision
      of a safe play area and the dangers of moving vehicles; a fridge magnet with dot
      points used to emphasis five farm based behaviours that address child safety; and
      a child farm safety educational resource kit developed by Farmsafe Queensland
      (Safety on the Land), which included activity sheets, stickers and a build-it
      yourself money-box. Focus group discussions were audiotaped, transcribed and
      analysed using qualitative interpretative methods. RESULTS: There was variance in
      the way children read meanings in child farm safety messages on the poster. In
      particular, there were misinterpretations of the messages portrayed in the poster
      by 7-9 years olds. Students found the Safety on the Land kit helpful for
      delivering the farm-safe message, due to its participatory format. The findings
      show that the use of cartoon style illustrations and comic formats to communicate
      child farm safety messages was positively perceived by the age groups in this
      sample. CONCLUSIONS: Farmsafe Australia's poster was open to varied
      interpretations by students, some of which missed the safety message altogether.
      The use of a broad communication tool such as a poster is problematic because it
      is displayed in public places which, by implication, reach a wide audience.
      Future design of farm safety communication tools should take into account the
      views of primary school children as a specific target audience. Students enjoyed
      the participatory nature of the Safety on the Land kit and made suggestions about
      how this tool could effect change in behaviour. The findings of the study also
      indicate the potential effectiveness of cartoon style illustrations and comic
      formats for delivering child farm safety messages to a target audience of 7-12
      year olds.

PMID- 18062741
TI  - Engaging rural communities in health care through a paramedic expanded scope of
      practice.
AB  - INTRODUCTION: This article explores how community engagement by paramedics in an
      expanded scope role contributes to both primary health care and to an overall
      improved emergency response capacity in rural communities. Understanding how
      expanded scope paramedics (ESP) can strengthen community healthcare
      collaborations is an important need in rural areas where low workforce numbers
      necessitate innovation. METHODS: Four examples of Australian rural ESP roles were
      studied in Tasmania, New South Wales, South Australia and Victoria to gather
      information on consistent elements that could inform a paramedic expanded scope
      model. Qualitative data were collected from semi-structured interviews with key
      stakeholders and organisational documents. Thematic analysis within and across
      cases found community engagement was a key element in the varied roles. This
      article relies heavily on data from the Victorian and Tasmanian case studies
      because community engagement was a particularly strong aspect of these cases.
      RESULTS: The ESP in the case studies increased interactions between ambulance
      services and rural communities with an overall benefit to health care through:
      increasing community response capacity; linking communities more closely to
      ambulance services; and increasing health promotion and illness prevention work
      at the community level. Leadership, management and communication skills are
      important for paramedics to successfully undertake expanded scope roles.
      CONCLUSION: ESP in rural locations can improve health care beyond direct clinical
      skill by active community engagement that expands the capacity of other community
      members and strengthens links between services and communities. As health
      services look to gain maximum efficiency from the health workforce, understanding
      the intensification of effort that can be gained from practitioner and community
      coalitions provides important future directions.

PMID- 18062742
TI  - Molecular therapeutic targets for bladder cancer.

PMID- 18062744
TI  - Multimodality management of brain metastases in metastatic melanoma patients.
AB  - Brain metastases are a frequent complication of advanced melanoma. Neurosurgery
      (generally followed by radiotherapy) may be useful in managing solitary,
      superficial brain metastases in good performance status patients, as well as for
      diagnostic purposes. Since most patients are not felt to be resectable and
      concurrent extracranial metastases frequently are present, whole-brain
      radiotherapy (WBRT) has become the de facto treatment standard. WBRT has resulted
      in disappointing outcomes, resulting in a 3.6-4.1-month median survival. Recent
      studies have suggested that focal irradiation using linear accelerator-based
      stereotactic radiosurgery or gamma-knife technologies can result in excellent
      local control and prolonged survival in some patients. It is possible that more
      aggressive combined modality treatment strategies, such as addition of systemic
      therapy, may further improve outcome. Current data suggest that aggressive
      treatment of patients with up to five brain melanoma brain metastases is capable
      of producing prolonged survival in many patients, including some long-term
      complete responses.

PMID- 18062745
TI  - Use of ultrasound to early identify, diagnose and localize metastases in melanoma
      patients.
AB  - Specialized medical centers perform high-resolution ultrasound of lymph nodes in
      melanoma patients to detect metastases early. Ultrasound represents a highly
      effective method for the discrimination of lymph node and soft-tissue metastases
      from other space-occupying lesions. Frequent follow-up examinations with
      ultrasound provide early detection of tumor recurrences and seem to lead to a
      prolonged overall survival. The ultrasound findings are validated by fine-needle
      aspiration cytology. Depicted and verified metastases should be removed as soon
      as possible. The authors recommend the performance of ultrasound before every
      sentinel lymph node dissection to avoid unnecessary operations.

PMID- 18062746
TI  - Molecular markers for bladder cancer: the road to a multimarker approach.
AB  - Bladder cancer is the seventh most common malignancy worldwide, with almost
      14,000 patients dying from this disease in the USA alone. Because of the need for
      long-term and frequent follow-up, as well as the paucity of sensitive and
      specific noninvasive tests, bladder cancer management has the highest cost per
      patient among all cancer types. Several molecular markers, especially members of
      the cell cycle regulation and apoptosis pathways, have been investigated.
      However, no individual marker has been prognostically powerful enough to change
      clinical management. The combined analysis of a panel of markers spanning
      different pathways is the most promising approach. We give an overview of the
      most important molecular markers functioning in crucial pathways and focus on
      their role in multimarker analysis.

PMID- 18062747
TI  - Current status of neoadjuvant and adjuvant chemotherapy for muscle-invasive
      bladder cancer.
AB  - Muscle-invasive transitional cell carcinoma occurs in approximately 30% of
      patients and is associated with a high risk of distant metastasis. Radical local
      therapy in the form of cystectomy or radiotherapy is curative in a portion of
      patients. Systemic therapy to treat occult micrometastasis at the time of local
      control is necessary to improve outcomes. Neoadjuvant chemotherapy is associated
      with a 5-6% improvement in overall survival at 5 years, and adjuvant chemotherapy
      may achieve similar results, although this remains unproven. Operative
      complications are not increased with neoadjuvant therapy. Perioperative treatment
      strategies remain underutilized, and many patients are not offered treatment to
      reduce the risk of relapse. Neoadjuvant strategies are a potent tool for research
      and should be employed to test new agents for the treatment of transitional cell
      carcinoma.

PMID- 18062748
TI  - Biomarkers in clear cell renal cell carcinoma.
AB  - The treatment of advanced renal cell carcinoma (RCC) has evolved significantly
      following the identification of the von Hippel-Lindau (VHL) gene and the function
      of its protein, and subsequent development of antiangiogenic therapies. A series
      of clinical trials resulted in the approval of three new agents with significant
      activity in this disease. Additional studies are now underway to identify subsets
      of patients most likely to benefit. This article reviews the current therapy for
      advanced RCC and the development of biomarkers in RCC. This requires the
      identification of disease characteristics at a clinical, genetic and molecular
      level associated with response and/or surrogate measures of clinical benefit.
      Currently, a variety of prognostic factors (lactate dehydrogenase, performance
      status, disease-free interval, hemoglobin and calcium levels) are utilized to
      predict the survival of RCC patients. The use of validated biomarkers in either
      serum/plasma, urine or tissue could enhance this process, as well as define at
      the molecular and genetic levels, factors associated with response to therapy
      and/or the development of resistance. Examples include plasma VEGF levels, VHL
      gene mutation status and carbonic anhydrase IX levels in tumor tissue, among
      others. Validation of such biomarkers is crucial in order for them to be
      clinically useful.

PMID- 18062749
TI  - Current status of cytoreductive nephrectomy in metastatic renal cell carcinoma.
AB  - The incidence of metastatic renal cell carcinoma (mRCC) continues to rise. While
      treatment options have increased dramatically in the last few years, few patients
      achieve a cure. The standard of care for mRCC in cytokine-eligible candidates is
      nephrectomy followed by high-dose IL-2. High-dose IL-2 can induce durable
      complete remissions, but only select patients can enjoy its benefits owing to
      toxicities. While not curative, the newer targeted therapies offer a broader
      patient population the chance for treatment response and prolonged survival. This
      review highlights the historical background of cytoreductive nephrectomy in mRCC,
      discusses the available treatment options and considers alternative treatment
      paradigms, such as the integration of the targeted agents with nephrectomy and
      the use of systemic therapy as medical selection for determining appropriate
      nephrectomy candidates.

PMID- 18062750
TI  - Cardiotoxicity associated with the use of trastuzumab in breast cancer patients.
AB  - The monoclonal antibody against HER2, trastuzumab (Herceptin), has become an
      important player in the treatment of patients with HER2-positive breast cancer.
      Both in the metastatic and adjuvant setting, the addition of trastuzumab to other
      systemic treatments has led to a striking increase in tumor response and
      survival. The downside with the use of this agent, however, is its inherent
      cardiotoxicity, which is particularly common when anthracyclines are used
      concurrently. This review will focus on all aspects of the cardiac side-effects
      of trastuzumab, ranging from epidemiology and pathophysiology to cardiac
      monitoring, and treatment and prevention.

PMID- 18062751
TI  - Treatment of bicalutamide-induced breast events.
AB  - Bicalutamide is a competitive nonsteroidal androgen receptor antagonist. In the
      European Union and a number of other countries, bicalutamide 150 mg per day is
      approved as an adjuvant to primary treatments (radical prostatectomy or
      radiotherapy) or as monotherapy as an alternative to surgical or medical
      castration in men with locally advanced, nonmetastatic prostate cancer. The
      ongoing bicalutamide Early Prostate Cancer (EPC) program has shown that breast
      events, defined as gynecomastia, breast pain or both, are a significant
      limitation of bicalutamide. Nearly 90% of patients experienced one or both
      symptoms and nearly 16% of patients withdrew from the EPC program as a
      consequence of bicalutamide-induced breast events. Tamoxifen, anastrozole and
      radiotherapy have all been studied as options for the treatment of breast events.
      To date, tamoxifen appears to be the superior agent in terms of outcomes;
      however, further studies are still required to determine the optimal dose and
      timing of tamoxifen administration for both prophylaxis and treatment. In
      addition, the impact on prostate cancer control remains uncertain. An ongoing
      clinical trial using toremifene to prevent morphometric vertebral fractures in
      men undergoing medical and/or surgical castration will provide some additional
      data on the effects of selective estrogen receptor modulators in men with
      prostate cancer.

PMID- 18062752
TI  - State-of-the-art mandible reconstruction using revascularized free-tissue
      transfer.
AB  - Mandible defects are created by trauma as well as ablative surgery for both
      benign and malignant tumors. Ablative surgery for malignant tumors creates
      complex defects that impact form and function. This is often further complicated
      by the use of chemotherapy and radiation. In order to achieve a highly functional
      reconstruction with an acceptable cosmetic result, patients must be properly
      evaluated preoperatively. A patient's performance status and expectations for
      postoperative form and function can impact reconstruction. Once the defect is
      created, both the bone and soft-tissue loss must be considered. A structured
      approach to mandible defects will enable the re-establishment of mandible
      continuity and optimal soft-tissue reconstruction. This will ultimately lead to a
      patient with oral competence and limited swallowing deficits, as well as the
      ability to communicate effectively and interact with their community in a
      meaningful manner. There are ongoing investigations into new techniques and
      materials, such as distraction osteogenesis and tissue engineering, which will
      hopefully advance our ability to reconstruct the mandible.

PMID- 18062753
TI  - Toward optimal health: Diane M. Harper, M.D., M.S., M.P.H., discusses the HPV
      vaccine and the prevention of cervical cancer. Interview by Jodi R. Godfrey.

PMID- 18062754
TI  - Social support networks and maternal mental health and well-being.
AB  - The link between social networks and mental health has increasingly been
      recognized by public health as an important topic of interest. In this paper, we
      explore this association among a specific group: mothers. Specifically, we
      discuss how maternal mental health can be understood in the context of social
      networks, the influence of specific social relationships, and how the type and
      quality of support can mediate maternal mental health outcomes. We review
      interventions that foster social networks to address maternal mental health as
      well as other related health outcomes. Findings suggest that interventions that
      combine multiple treatment approaches may be more effective in addressing mental
      health. Also, traditional measures of social networks may not be appropriate for
      vulnerable populations, with qualitative, rather than quantitative, indicators of
      social networks being more predictive of maternal health and well-being. The
      implications of these findings and future research directions are discussed.

PMID- 18062755
TI  - HIV and menopause: a review.
AB  - The use of highly active antiretroviral therapy (HAART) has resulted in dramatic
      reductions in morbidity and mortality of HIV infected individuals. With
      increasing life expectancy, a growing population of women will experience
      menopausal transitions while infected with HIV. Changes associated with menopause
      may affect HIV disease progression, and HIV-infected women may experience
      menopause in a different way from that of uninfected women. Age at natural
      menopause among non-HIV-infected white and Hispanic women is on the average 51
      years, and that of African American women is 49 years. Several studies have shown
      that the mean age of menopause in HIV-infected women is 47-48 years. This is
      likely due to factors other than HIV infection that predict early menopause, such
      as drug use, smoking, and low socioeconomic status. It may be difficult to
      separate out HIV symptoms from menopausal symptoms. The additive effects of
      menopause, HIV infection, and HAART on changes involving bone, lipid, and glucose
      metabolism need further investigation. Likewise, there is a need for a better
      understanding of the prevalence and manifestations of depression among these
      women.

PMID- 18062756
TI  - Increased risk of infection and mortality in women after cardiac surgery related
      to allogeneic blood transfusion.
AB  - BACKGROUND: Infection and mortality rates are greater in women than in men after
      cardiac surgery. This study was conducted to assess whether allogeneic blood
      transfusion could partially account for this gender difference, as transfusion
      has been associated with immunomodulation. METHODS: A cohort study was conducted
      in 380 patients at the University of Rochester Medical Center. Subjects were
      adult patients who underwent primary coronary artery bypass graft (CABG) surgery,
      primary valve replacement surgery, or both. Information was collected about blood
      components transfused, as well as postoperative infection, pulmonary dysfunction,
      and in-hospital mortality. RESULTS: Women were more likely to receive allogeneic
      red blood cells (RBCs) or platelets than men (odds ratio [OR] 21.6, 95% CI 3.8,
      124.2) and a greater quantity of blood than men. Patients who received allogeneic
      blood were 4.4 times more likely to develop an infection than those who did not
      (95% CI 1.5, 13.2). There was a positive linear correlation between number of
      units of blood received and number of days with fever (p<0.001) and hospital
      length of stay (p<0.001). This was particularly evident in patients who received
      four or more units of nonleukoreduced blood components. Women had a greater risk
      of infection (p=0.005), pulmonary dysfunction (p=0.005), and mortality (p=0.007)
      than men during hospitalization. CONCLUSIONS: One reason for the greater
      mortality in women after cardiac surgery may be the increased likelihood of
      receiving nonleukoreduced allogeneic RBCs and platelets. Transfusion increased
      the risk of infection; infection, then, increased the likelihood of pulmonary
      dysfunction and mortality.

PMID- 18062757
TI  - Inconsistent health perceptions for US women and men with diabetes.
AB  - BACKGROUND: Two health status measures for adults with diabetes are compared in
      order to identify gender-based differences between norm-based scores for health
      status and self-rated health scores. METHODS: Data were obtained from the 2001
      and 2003 Medical Expenditure Panel Survey(MEPS). Diabetes was identified by self
      report or ICD-9 code. Demographic and clinical (e.g., body mass index [BMI],
      comorbidities) parameters were included. Outcomes were norm-based measures of
      physical and mental health (SF-12 Physical and Mental Component Scores: SF-12 PCS
      and SF-12 MCS) and self-rated perception of health status. Sex-based differences
      in the three outcome measures, SF-12 PCS, SF-12 MCS, and self-rated health
      scores, were evaluated in univariate analyses and multivariate linear regression
      for survey data. RESULTS: A cohort of 3640 respondents with diabetes was
      identified (2037 women, 1603 men). In unadjusted analyses, women were older than
      men (60.7 vs. 59.3 years, p<0.001), reported higher mean BMI (31.1 vs. 30.4),
      more comorbidities, depression, and physical limitations (all p<0.001), had
      poorer SF-12 MCS scores (p=0.01), and self-rated their health status
      significantly higher than did men (p<0.01). In adjusted analyses, female gender
      was associated with lower SF-12 MCS scores and higher self-rated health scores.
      No factors were positively associated with higher scores across all three
      measures; only cognitive limitations consistently predicted lower health status
      scores in all three measures. CONCLUSIONS: Among adults with diabetes in a
      nationally representative sample of the U.S. adult population, discrepancies
      exist in health status measures. Despite being older, having more comorbidities
      and physical limitations, and lower norm-based scores for mental functional
      status, women self-rate their own health status higher than do men. Further
      research into the gender-based determinants and clinical implications of self
      rated health status is warranted.

PMID- 18062758
TI  - Patient acceptability of manual versus electric vacuum aspiration for early
      pregnancy loss.
AB  - OBJECTIVE: To compare the safety, efficacy, postprocedure quality of life, and
      acceptability of manual vacuum aspiration (MVA) performed as an outpatient with
      electric vacuum aspiration (EVA) performed in a hospital in women experiencing a
      first-trimester miscarriage. METHODS: From a randomized multicenter trial
      comparing misoprostol with vacuum aspiration for first-trimester loss, data were
      extracted comparing the safety, efficacy, and acceptability of MVA in an office
      setting with local anesthesia with EVA in an operating room environment with
      spinal or general anesthesia or monitored anesthesia care (MAC). RESULTS: One
      hundred fifty-seven women underwent EVA or MVA. Efficacy and safety were similar
      in both groups. Physical and emotional role functioning scores were better in
      patients undergoing MVA (p=0.01), and fewer patients undergoing MVA missed work
      or required help at home (p<0.01). However, pain severity scores were better in
      the EVA arm of the study (p=0.03). There was a trend toward fewer MVA patients
      recommending or using this procedure again. CONCLUSIONS: In patients with early
      pregnancy loss, treatment with MVA as an outpatient with local anesthesia is an
      effective and safe alternative to EVA performed in a hospital with conscious
      sedation or spinal or general anesthesia. Treatment in the outpatient setting
      allows for a better physical and emotional quality of life postprocedure.

PMID- 18062759
TI  - Circumstances and consequences of falls in community-dwelling older women.
AB  - AIMS: To describe the circumstances and consequences of falls reported by
      community-dwelling older women. METHODS: This prospective study collected data
      for approximately 2 years for women aged>or=70 years at risk for falling who were
      enrolled in the Fall Evaluation and Prevention Program. RESULTS: Participants
      (263) completed a median of 24 months of follow-up. A total of 143 participants
      reported 341 falls; 70 reported 1 fall, and 73 reported 2 or more. A majority of
      falls (62%) occurred in/around the home, primarily during the daytime, and in
      living rooms or kitchens/dining rooms. Falls frequently occurred while walking,
      carrying objects, or reaching/leaning. Many falls did not result in injury (53%);
      however, 31% resulted in minor injuries, 10% in moderate injuries, and 6% in
      major injuries. Soft tissue injuries were common, and 5% of falls resulted in
      fractures. Nine falls resulted in hospitalization. CONCLUSIONS: The high rate of
      injurious falls seen here and the detailed information on activity at the time of
      the fall emphasize the need to increase awareness of behaviors and the
      environment to reduce fall risk. Previous studies have identified risk factors
      for falls, some of which cannot be modified, such as age or gender. In contrast,
      this study describes the activity at the time of the fall: many falls occur in
      the home environment, some with modifiable circumstances.

PMID- 18062760
TI  - Cervical cancer screening among foreign-born women by birthplace and duration in
      the United States.
AB  - OBJECTIVE: Mortality rates for cervical cancer have increased among foreign-born
      women in the United States in the last two decades. Previous research indicates
      that rates of Pap testing are lower among foreign-born women than in U.S.-born
      women. This study identifies screening rates among foreign-born women by
      birthplace and duration in the United States. METHODS: We used data from 4 years
      (1998, 1999, 2000, 2003) of the National Health Interview Survey (NHIS) to
      estimate Pap testing rates by birthplace (Mexico, Central America, Caribbean,
      South America, Europe, Russia, Africa, Middle East, India, Asia, and Southeast
      Asia) and percent of lifetime spent in the United States for women aged>or=18
      years (n=70,775). Rates were age standardized to the 2000 U.S. population.
      RESULTS: After adjusting for demographic characteristics and health indicators,
      we found that 18.6% (95% CI 16.7, 20.6) of recent immigrants (<25% of lifetime in
      the United States) and 9.9% (95% CI 9.0, 10.8) of established immigrants (>or=25%
      of lifetime in the United States)never received a Pap test in their lifetime
      compared with 5.8% (95% CI 5.5, 6.1) of U.S.-born women. Adjusted prevalence of
      never receiving a Pap test was highest among women from Asia, Southeast Asia, and
      India (19.6%), South America (12.7%), Mexico (11.2%), Caribbean (11.0%), Europe
      (9.9%), and Central America (9.2%). CONCLUSIONS: Significant differences exist in
      rates of screening for cervical cancer between foreign-born groups by birthplace
      and by duration in the United States. Nationally and locally funded screening
      programs may benefit from these findings in developing screening strategies for
      foreign-born women.

PMID- 18062762
TI  - Latinas with abnormal breast findings: patient predictors of timely diagnostic
      resolution.
AB  - BACKGROUND: Incomplete or delayed diagnostic resolution of breast abnormalities
      suspicious for cancer may contribute to poor breast cancer outcomes among ethnic
      minority women. We examine the effects of socioeconomic characteristics,
      knowledge, barriers to healthcare, communication, and clinical variables on
      diagnostic resolution in Latina women with breast abnormalities at two Los
      Angeles County public hospitals. METHODS: We analyzed telephone survey data for
      714 women. The outcome--timely diagnostic resolution--was based on medical record
      data and defined as receipt of a definitive diagnosis (malignant or benign)
      within 6 months of the index referral. Predictors of the outcome were obtained
      from a telephone survey and examined with bivariate and multivariable logistic
      regression models. RESULTS: Only 60% of women received timely diagnostic
      resolution; however, the proportion was higher at hospital B (73%) compared with
      hospital A (56%). In the total sample, the odds of timely diagnostic resolution
      increased by 8% for every point increase in the scale of satisfaction with how
      physicians explained the breast abnormality. At hospital B, the odds of timely
      resolution increased by 57% for every 10-year increase in age. CONCLUSIONS:
      Consistent with findings of other studies, our data indicate low diagnostic
      resolution among Latina women. Satisfaction with how physicians explained breast
      abnormalities and the interaction of hospital with age affected timely diagnostic
      resolution. Future research might focus on developing interventions that offer
      concrete communication strategies to patients and providers. Health systems must
      also establish systems that facilitate effective patient-provider communication.

PMID- 18062761
TI  - Microbicides: information, beliefs, and preferences for insertion.
AB  - OBJECTIVES: Microbicides are products in development to prevent sexually
      transmitted infection and HIV acquisition; they are not yet available to the
      public. We evaluated (1) where women would expect to seek information about
      microbicides, (2) factors that women think might affect microbicide
      effectiveness, and (3) women's anticipated preferences for timing and place of
      insertion and partner involvement. METHODS: A cross-sectional face-to-face
      interview was administered to women aged 18-35 years (n=126) recruited from a
      gynecology clinic in Galveston, Texas. Women were shown a microbicide surrogate
      and asked to complete a series of closed-ended questions focusing on
      demographics, expected sources of information on microbicides, perceived factors
      related to effectiveness, and preferences for timing and place of insertion and
      level of partner involvement. Univariate descriptive analyses were used to
      calculate means, medians, and frequencies. RESULTS: Women's most cited
      anticipated sources of information for microbicides were physicians (89%), the
      package insert/box (86%), and pharmacists (70%). Approximately two thirds of the
      women believed that menstruation or taking other medicines and approximately one
      third believed that taking a bath/shower before intercourse or after intercourse
      or using birth control medication could limit effectiveness. Women anticipated
      preferring to insert the microbicide before intercourse (90%) and while in the
      bathroom (73%). Most (95%) anticipated telling their partners they planned to use
      a microbicide, and 38% anticipated having their partner insert the product for
      them. CONCLUSIONS: Women's beliefs about those factors that could limit
      effectiveness of microbicides should be addressed as part of anticipatory
      guidance or in the package inserts. Partners likely will be involved in the use
      of microbicides; thus, education/marketing efforts should also incorporate
      partner beliefs and preferences.

PMID- 18062763
TI  - Characteristics of women seeking intensive outpatient substance use treatment in
      the VA.
AB  - OBJECTIVES: To investigate gender differences among veterans receiving intensive
      outpatient (IOP) substance use treatment in a national VA sample and to compare
      women attending IOP with women with substance use disorders in VA primary care.
      METHODS: VA national databases were used to identify all veterans receiving
      intensive IOP substance use treatment in 1999 along with a matched cohort of
      individuals with substance use disorders attending primary care but not in
      treatment. RESULTS: Few women (2.8%) were treated in IOP at the VA. Among the
      women who did receive treatment, substantial clinical differences were found
      compared with men in IOP treatment. Women with substance use disorders were
      younger, more likely to have cocaine abuse or dependence disorders, and more
      likely to have extensive psychiatric and medical comorbidities than men with
      substance use disorders in the VA. Women in treatment were also found to be
      significantly different from women with substance use disorders not in treatment.
      CONCLUSIONS: Outreach and new programming for women veterans with substance use
      disorders in the VA is critical in order to treat these issues early and
      potentially prevent multiple, severe comorbid illnesses.

PMID- 18062764
TI  - Health needs and barriers to healthcare of women who have experienced intimate
      partner violence.
AB  - BACKGROUND: This study assessed the health needs and barriers to healthcare among
      women with a history of intimate partner violence (IPV) as told by women
      themselves. METHODS: Qualitative interviews were conducted with 25 women clients
      and 10 staff members at a crisis center in metropolitan North Carolina. Clients
      also completed a structured survey. RESULTS: Eleven shelter clients and 14 walk
      ins completed the survey and interview. Client participants were demographically
      mixed, and 20% were Spanish-speaking immigrants. Most clients were unemployed and
      uninsured. Women reported worse health in the interviews than on the surveys;
      clients' major health needs were chronic pain, chronic diseases, and mental
      illness. Reported barriers to healthcare were cost, psychological control by the
      abuser, and low self-esteem and self-efficacy. Staff's perceptions of clients
      health needs differed from clients,' focusing on reproductive health,
      HIV/sexually transmitted infection (STI), mental illness, and inadequate
      preventive healthcare. Staff and clients' perceptions of barriers to healthcare
      were more congruent. Suggestions for improving the center's response were to
      offer more health education groups and more health-related staff trainings.
      Agency barriers to implementing these changes were limited funding, focus on
      crisis management, and perceived disconnect with the healthcare system.
      CONCLUSIONS: Health needs of women who have experienced IPV are significant and
      include physical and mental concerns. IPV creates unique barriers to accessing
      healthcare, which can be addressed only partially by a crisis center. Greater
      coordination with the healthcare system is needed to respond more appropriately
      to the health needs of women who have experienced IPV.

PMID- 18062765
TI  - Intervention study of exercise for depressive symptoms in women.
AB  - BACKGROUND AND OBJECTIVES: Clinical depression affects millions of women
      annually. Exercise has been studied as a potential antidepressant, with most
      studies supporting its efficacy. Exercise also has the potential to reduce the
      risk for physical comorbidities that occur with depression. However, less is
      known about the types of exercise programs to which women with depressive
      symptoms will adhere. Our objectives were to (1) compare two exercise programs,
      varying in their degree of structure, on improvements in physical activity and
      (2) compare the two exercise interventions on depressive symptoms, body
      composition, and fitness. METHODS: Women with depressive symptoms (physician
      diagnosed and confirmed with the Beck Depression Inventory) residing in the
      greater Boston area were recruited for this 3-month intervention study.
      Continuous enrollment took place between November 2005 and November 2006. Women
      were randomly assigned to either a clinic-based or home-based exercise
      intervention, with assessments at baseline and 3-months. RESULTS: Participants
      (n=32) were predominantly minority (81.4%) and, at baseline, had moderate
      symptoms of depression (Beck Depression Inventory [BDI], mean=25.6, SD=9.3), and
      were sedentary (mean=35.8 min/week of moderate and vigorous activity, SD=31.4).
      Gain scores for depressive symptoms (clinic-based mean=-11.7, home-based mean=
      9.7) and physical activity (clinic-based mean=65.4, home-based mean=39.0)
      indicate strong improvements across time. Intent-to-treat analyses on 3-month
      data show that both interventions were associated with improvements in time spent
      in physical activity and depressive symptoms. Neither intervention impacted body
      composition or fitness. CONCLUSIONS: Both exercise programs were associated with
      reductions in depressive symptoms and increased physical activity participation,
      suggesting that even a home-based program can benefit women with depressive
      symptoms.

PMID- 18062766
TI  - Effect of the summer months on body weight and composition in college women.
AB  - BACKGROUND AND OBJECTIVES: College students and young adults are experiencing the
      greatest increases in rates of obesity, and 20% of college students are
      classified as obese. The objective of this study was to compare changes and rates
      of change in body weight and body composition between the freshman academic year
      and the summer after the freshman year among female college students. METHODS:
      Participants were recruited early in their freshman year of college to
      participate in a prospective longitudinal study examining changes in body weight
      and composition over the college years. Height and weight were measured, and body
      composition was assessed using dual energy x-ray absorptiometry (DEXA) at the
      beginning and end of the freshman year. Upon return from the summer for their
      sophomore year, participants returned to have all measurements repeated. Sixty
      nine female participants completed all three visits. RESULTS: Body weight
      increased 1.3 kg during the academic period and an additional 0.1 kg during the
      summer period. Body mass index (BMI) increased between the first two visits but
      did not change between the last two visits. However, percent fat increased at
      each visit. Fat-free mass significantly increased 0.5 kg over the academic year
      but decreased by 1.1 kg over the summer (p<0.05). Greater rates of change were
      detected in percent fat, fat-free mass, and BMI during the summer compared with
      the academic year (p<0.05). CONCLUSIONS: Differences in body composition between
      the academic and summer periods may reflect changes in living situations between
      these periods. Unfavorable changes during the summer suggest the need to promote
      healthy lifestyles to freshman women before they leave campus for the summer.

PMID- 18062768
TI  - The biology of interleukin-2.
AB  - Much data support an essential role for interleukin (IL)-2 in immune tolerance.
      This idea is much different from the early paradigm in which IL-2 is central for
      protective immune responses. This change in thinking occurred when a T regulatory
      cell defect was shown to be responsible for the lethal autoimmunity associated
      with IL-2/IL-2R deficiency. This realization allowed investigators to explore
      immune responses in IL-2-nonresponsive mice rendered autoimmune-free. Such
      studies established that IL-2 sometimes contributes to optimal primary immune
      responses, but it is not mandatory. Emerging findings, however, suggest an
      essential role for IL-2 in immune memory. Here, the current understanding of the
      dual role of IL-2 in maintaining tolerance and contributing to immunity in vivo
      is reviewed with some emphasis on T regulatory cell production and homeostasis.
      Also discussed are implications of this new appreciation concerning the
      immunobiology of IL-2 with respect to targeting IL-2 or its receptor in
      immunotherapy.

PMID- 18062769
TI  - Multiscale simulation of soft matter: from scale bridging to adaptive resolution.
AB  - The relation between atomistic chemical structure, molecular architecture,
      molecular weight, and material properties is of basic concern in modern soft
      material science and includes standard properties of bulk materials and surface
      and interface aspects, as well as the relation between structure and function in
      nanoscopic objects and molecular assemblies of both synthetic and biological
      origin. This all implies a thorough understanding on many length and
      correspondingly time scales, ranging from (sub)atomistic to macroscopic.
      Presently, computer simulations play an increasingly important, if not central,
      role. Some problems do not require specific atomistic details, whereas others
      require them only locally. However, in many cases this strict separation is not
      sufficient for a comprehensive understanding of systems, and flexible simulation
      schemes are required that link the different levels of resolution. We here give a
      general view of the problem regarding soft matter and discuss some specific
      examples of linked simulation techniques at different resolution levels. We then
      discuss a recently developed flexible simulation scheme, the AdResS method, which
      allows one to adaptively change the resolution in certain regions of space on
      demand.

PMID- 18062770
TI  - Diacylglycerol kinases: at the hub of cell signalling.
AB  - DGKs (diacylglycerol kinases) are members of a unique and conserved family of
      intracellular lipid kinases that phosphorylate DAG (diacylglycerol), catalysing
      its conversion into PA (phosphatidic acid). This reaction leads to attenuation of
      DAG levels in the cell membrane, regulating a host of intracellular signalling
      proteins that have evolved the ability to bind this lipid. The product of the DGK
      reaction, PA, is also linked to the regulation of diverse functions, including
      cell growth, membrane trafficking, differentiation and migration. In
      multicellular eukaryotes, DGKs provide a link between lipid metabolism and
      signalling. Genetic experiments in Caenorhabditis elegans, Drosophila
      melanogaster and mice have started to unveil the role of members of this protein
      family as modulators of receptor-dependent responses in processes such as
      synaptic transmission and photoreceptor transduction, as well as acquired and
      innate immune responses. Recent discoveries provide new insights into the complex
      mechanisms controlling DGK activation and their participation in receptor
      regulated processes. After more than 50 years of intense research, the DGK
      pathway emerges as a key player in the regulation of cell responses, offering new
      possibilities of therapeutic intervention in human pathologies, including cancer,
      heart disease, diabetes, brain afflictions and immune dysfunctions.

PMID- 18062771
TI  - Mitochondria and cellular oxygen sensing in the HIF pathway.
AB  - Mitochondrial respiration is responsible for more than 90% of oxygen consumption
      in humans. Cells utilize oxygen as the final electron acceptor in the aerobic
      metabolism of glucose to generate ATP which fuels most active cellular processes.
      Consequently, a drop in tissue oxygen levels to the point where oxygen demand
      exceeds supply (termed hypoxia) leads rapidly to metabolic crisis and represents
      a severe threat to ongoing physiological function and ultimately, viability.
      Because of the central role of oxygen in metabolism, it is perhaps not surprising
      that we have evolved an efficient and rapid molecular response system which
      senses hypoxia in cells, leading to the induction of an array of adaptive genes
      which facilitate increased oxygen supply and support anaerobic ATP generation.
      This response is governed by HIF (hypoxia-inducible factor). The oxygen
      sensitivity of this pathway is conferred by a family of hydroxylases which
      repress HIF activity in normoxia allowing its rapid activation in hypoxia.
      Because of its importance in a diverse range of disease states, the mechanism by
      which cells sense hypoxia and transduce a signal to the HIF pathway is an area of
      intense investigation. Inhibition of mitochondrial function reverses hypoxia
      induced HIF leading to speculation of a role for mitochondria in cellular oxygen
      sensing. However, the nature of the signal between mitochondria and oxygen
      sensing hydroxylase enzymes has remained controversial. In the present review,
      two models of the role for mitochondria in oxygen sensing will be discussed and
      recent evidence will be presented which raises the possibility that these two
      models which implicate ROS (reactive oxygen species) and oxygen redistribution
      respectively may complement each other and facilitate rapid and dynamic
      activation of the HIF pathway in hypoxia.

PMID- 18062772
TI  - Getting to grips with the plant metabolic network.
AB  - Research into plant metabolism has a long history, and analytical approaches of
      ever-increasing breadth and sophistication have been brought to bear. We now have
      access to vast repositories of data concerning enzymology and regulatory features
      of enzymes, as well as large-scale datasets containing profiling information of
      transcripts, protein and metabolite levels. Nevertheless, despite this wealth of
      data, we remain some way off from being able to rationally engineer plant
      metabolism or even to predict metabolic responses. Within the past 18 months,
      rapid progress has been made, with several highly informative plant network
      interrogations being discussed in the literature. In the present review we will
      appraise the current state of the art regarding plant metabolic network analysis
      and attempt to outline what the necessary steps are in order to further our
      understanding of network regulation.

PMID- 18062773
TI  - ODCp, a brain- and testis-specific ornithine decarboxylase paralogue, functions
      as an antizyme inhibitor, although less efficiently than AzI1.
AB  - ODC (ornithine decarboxylase), the first enzyme in the polyamine biosynthesis
      pathway in mammalian cells, is a labile protein. ODC degradation is stimulated by
      Az (antizyme), a polyamine-induced protein, which in turn is regulated by an ODC
      related protein termed AzI (Az inhibitor). Recently, another ODCp (ODC paralogue)
      was suggested to function as AzI, on the basis of its ability to increase ODC
      activity and inhibit Az-stimulated ODC degradation in vitro. We show in the
      present study that ODCp is indeed capable of negating Az functions, as reflected
      by its ability to increase ODC activity and polyamine uptake and by its ability
      to provide growth advantage in stably transfected cells. However, ODCp is less
      potent than AzI1 in stimulating ODC activity, polyamine uptake and growth rate.
      The superiority of AzI1 to ODCp in inhibiting the Az-stimulated ODC degradation
      is also demonstrated using an in vitro degradation assay. We show that the basis
      for the inferiority of ODCp as an AzI is its lower affinity towards Az (Az1 and
      Az3). Further, we show here that ODCp, like AzI, is degraded in a ubiquitin
      dependent manner, in a reaction that does not require either interaction with Az
      or the integrity of its C-terminus. Interaction with Az actually stabilizes ODCp
      by interfering with its ubiquitination. This results in sequestration of Az into
      a stable complex with ODCp, which is the central feature contributing to the
      ability of ODCp to function as AzI.

PMID- 18062774
TI  - Endothelin, sex and hypertension.
AB  - The ETs (endothelins) comprise a family of three 21-amino-acid peptides (ET-1, ET
      2 and ET-3) and 31-amino-acid ETs (ET-1(1-31), ET-2(1-31) and ET-3(1-31)). ET-1
      is synthesized from a biologically inactive precursor, big ET-1, by ECEs (ET
      converting enzymes). The actions of ET-1 are mediated through activation of the G
      protein-coupled ET(A) and ET(B) receptors, which are found in a variety of cells
      in the cardiovascular and renal systems. ET-1 has potent vasoconstrictor,
      mitogenic, pro-inflammatory and antinatriuretic properties, which have been
      implicated in the pathophysiology of a number of cardiovascular diseases.
      Overexpression of ET-1 has been consistently described in salt-sensitive models
      of hypertension and in models of renal failure, and has been associated with
      disease progression. Sex differences are observed in many aspects of mammalian
      cardiovascular function and pathology. Hypertension, as well as other
      cardiovascular diseases, is more common in men than in women of similar age. In
      experimental models of hypertension, males develop an earlier and more severe
      form of hypertension than do females. Although the reasons for these differences
      are not well established, the effects of gonadal hormones on arterial, neural and
      renal mechanisms that control blood pressure are considered contributing factors.
      Sex differences in the ET-1 pathway, with males displaying higher ET-1 levels,
      greater ET-1-mediated vasoconstrictor and enhanced pressor responses in
      comparison with females, are addressed in the present review. Sex-associated
      differences in the number and function of ET(B) receptors appear to be
      particularly important in the specific characteristics of hypertension between
      females and males. Although the gonadal hormones modulate some of the differences
      in the ET pathway in the cardiovascular system, a better understanding of the
      exact mechanisms involved in sex-related differences in this peptidergic system
      is needed. With further insights into these differences, we may learn that men
      and women could require different antihypertensive regimens.

PMID- 18062775
TI  - Therapeutic potential of stem cells in lung disease: progress and pitfalls.
AB  - There has been increasing excitement over the last few years with the suggestion
      that exogenous stem cells may offer new treatment options for a wide range of
      diseases. Within respiratory medicine, these cells have been shown to have the
      ability to differentiate and function as both airway and lung parenchyma
      epithelial cells in both in vitro and increasingly in vivo experiments. The
      hypothesis is that these cells may actively seek out damaged tissue to assist in
      the local repair, and the hope is that their use will open up new cellular and
      genetic treatment modalities. Such is the promise of these cells that they are
      being rushed from the benchside to the bedside with the commencement of early
      clinical trials. However, important questions over their use remain and the field
      is presently littered with controversy and uncertainty. This review evaluates the
      progress made and the pitfalls encountered to date, and critically assesses the
      evidence for the use of stem cells in lung disease.

PMID- 18062776
TI  - Can rodent models of diabetic kidney disease clarify the significance of early
      hyperfiltration?: recognizing clinical and experimental uncertainties.
AB  - In the past, hyperfiltration and increased glomerular capillary pressure have
      been identified as important determinants of the development of DN (diabetic
      nephropathy). Recently, some basic research and clinical reviews on DN have
      omitted identifying hyperfiltration as an important risk factor. At the same
      time, different rodent models of DN have been described without and with
      documented hyperfiltration. In the present review, the importance of
      hyperfiltration is reassessed, reviewing key clinical and research studies,
      including the first single nephron studies in a mouse model of DN. From clinical
      studies of Type 1 and Type 2 diabetes mellitus, it is clear that many patients do
      not have early hyperfiltration and, even when present, its contribution to
      subsequent DN remains uncertain. Key mechanisms underlying hyperfiltration in
      rodent models are reviewed. Findings on intrarenal NO metabolism and the control
      of single-nephron GFR (glomerular filtration rate) in rodent models of DN are
      also presented. Characterization of valid experimental models of DN should
      include a careful delineation of the absence or presence of early
      hyperfiltration, with special efforts made to establish the specific role
      hyperfiltration may play in the emergence of DN.

PMID- 18062777
TI  - Crystal structure and kinetic study of dihydrodipicolinate synthase from
      Mycobacterium tuberculosis.
AB  - The three-dimensional structure of the enzyme dihydrodipicolinate synthase (KEGG
      entry Rv2753c, EC 4.2.1.52) from Mycobacterium tuberculosis (Mtb-DHDPS) was
      determined and refined at 2.28 A (1 A=0.1 nm) resolution. The asymmetric unit of
      the crystal contains two tetramers, each of which we propose to be the functional
      enzyme unit. This is supported by analytical ultracentrifugation studies, which
      show the enzyme to be tetrameric in solution. The structure of each subunit
      consists of an N-terminal (beta/alpha)(8)-barrel followed by a C-terminal alpha
      helical domain. The active site comprises residues from two adjacent subunits,
      across an interface, and is located at the C-terminal side of the (beta/alpha)(8)
      barrel domain. A comparison with the other known DHDPS structures shows that the
      overall architecture of the active site is largely conserved, albeit the proton
      relay motif comprising Tyr(143), Thr(54) and Tyr(117) appears to be disrupted.
      The kinetic parameters of the enzyme are reported: K(M)(ASA)=0.43+/-0.02 mM,
      K(M)(pyruvate)=0.17+/-0.01 mM and V(max)=4.42+/-0.08 micromol x s(-1) x mg(-1).
      Interestingly, the V(max) of Mtb-DHDPS is 6-fold higher than the corresponding
      value for Escherichia coli DHDPS, and the enzyme is insensitive to feedback
      inhibition by (S)-lysine. This can be explained by the three-dimensional
      structure, which shows that the (S)-lysine-binding site is not conserved in Mtb
      DHDPS, when compared with DHDPS enzymes that are known to be inhibited by (S)
      lysine. A selection of metabolites from the aspartate family of amino acids do
      not inhibit this enzyme. A comprehensive understanding of the structure and
      function of this important enzyme from the (S)-lysine biosynthesis pathway may
      provide the key for the design of new antibiotics to combat tuberculosis.

PMID- 18062778
TI  - Plk3 phosphorylates topoisomerase IIalpha at Thr(1342), a site that is not
      recognized by Plk1.
AB  - The Plk (polo-like kinase) family is involved in cell-cycle machinery. Despite
      the possible overlapping involvement of Plk1 and Plk3 in cell-cycle distribution,
      the precise role of each Plk might be different. To investigate mechanisms that
      may differentiate their physiological roles, we compared the substrate
      specificities of Plk1 and Plk3 using synthetic peptides. Among these substrate
      peptides, topoisomerase IIalpha EKT(1342)DDE-containing synthetic peptide was
      strongly phosphorylated by Plk3 but not by Plk1. By modulating the topoisomerase
      IIalpha peptide, we identified residues at positions +1, +2 and +4 as
      determinants of differential substrate recognition between Plk1 and Plk3. Acidic
      residues at positions +2 and +4 appear to be a positive determinant for Plk3 but
      not Plk1. Variation at position +1 appears to be tolerated by Plk3, while a
      hydrophobic residue at +1 is critical for Plk1 activity. The direct
      phosphorylation of Thr(1342) of topoisomerase IIalpha by Plk3 was demonstrated
      with an in vitro kinase assay, and overexpression of Plk3 induced the
      phosphorylation of Thr(1342) in cellular topoisomerase IIalpha. Furthermore, the
      physical interaction between Plk3 and topoisomerase IIalpha was also demonstrated
      in cells in addition to phosphorylation. These data suggest that topoisomerase
      IIalpha is a novel physiological substrate for Plk3 and that Plk1 and Plk3 play
      different roles in cell-cycle regulation.

PMID- 18062779
TI  - Phosphorylated ITIMs enable ubiquitylation of an inhibitory cell surface
      receptor.
AB  - Immune responses are modulated by activating and inhibitory receptors that
      traffic to and from the cell surface. Ligands that bind to inhibitory receptors
      induce phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIMs)
      in their cytoplasmic tails, followed by recruitment of inhibitory signaling
      molecules. Mechanisms that control the surface levels of inhibitory receptors are
      largely unexplored. Here, we show, using CD33/sialic acid-binding immunoglobulin
      like lectin (Siglec)-3 as a paradigm, that ITIMs can bind to the ubiquitin ligase
      Cbl and that ITIMs are ubiquitylated following Src family kinase-mediated
      tyrosine phosphorylation. Ubiquitylation is a known signal for endocytosis.
      Accordingly, cells expressing CD33 mutants that cannot become ubiquitylated show
      significantly increased cell surface expression of CD33 and have impaired CD33
      internalization, whereas in-frame fusion of ubiquitin to CD33 reverses this
      phenotype. Our results identify a novel function of ITIMs and demonstrate that
      phosphorylation-dependent ubiquitylation regulates cell surface expression and
      internalization, and thus possibly function, of CD33/Siglec-3, suggesting an
      important role of ubiquitin in endocytosis of ITIM-bearing inhibitory
      immunoreceptors.

PMID- 18062780
TI  - Emergency department staff and susceptibility to pertussis: a seroprevalence
      study.
AB  - OBJECTIVE: To determine the proportion of ED staff who are susceptible to
      pertussis. There was evidence that some winter leave in southern Tasmania might
      be a reason of pertussis infection among unimmunized staff. This results in loss
      of individual earning and loss of availability of staff during the peak demand
      periods in the ED. There is evidence in the literature that underdiagnosis and
      undertreatment of pertussis occurs worldwide. METHODS: All ED staff were
      approached to participate in this seroprevalence study. A self-completed
      questionnaire was used to record pervious immunization history for pertussis.
      Blood samples were collected and analysed to detect and quantify immunoglobulin G
      and immunoglobulin A titres for pertussis. All confidence intervals (CI) are at
      95%. SETTINGS: The Royal Hobart Hospital and the co-located Hobart Private
      Hospital. RESULTS: Ninety-seven of 106 eligible staff took part in the present
      study, a participation rate of 92% (CI 84-96). Ninety-one of 97 subjects (94%, CI
      87-98) believed that they had been immunized for pertussis in childhood; six
      subjects had either not been immunized or were unsure (6%, CI 2-13). Twenty-three
      subjects (24%, CI 16-33) had been immunized as adults. There was serologic
      evidence of recent infection for 21 participants (22%, CI 14-31). Thirty-one
      participants (32%, CI 23-42) were susceptible to pertussis on the basis of low
      immunoglobulin G titres. CONCLUSION: ED staff should routinely be offered booster
      immunization for pertussis.

PMID- 18062781
TI  - Variables that predict admission to hospital from an emergency department
      observation unit.
AB  - OBJECTIVE: To determine factors predictive for patients requiring ongoing
      hospital admission from the emergency department observation unit (EDOU).
      METHODS: Prospective observational study on all patients admitted to the EDOU
      over 3 months. The primary outcome measure was patients requiring subsequent
      admission to hospital from the EDOU. RESULTS: Of 860 EDOU admissions occurring
      from 8337 ED presentations, 145 (16.9%) were subsequently admitted as inpatients.
      Of all analysed variables, four (inability to independently mobilize in the ED,
      requiring ongoing active treatment while in the EDOU, requiring referral to
      another subspecialty prior to transfer to the EDOU and requiring
      multidisciplinary allied health assessment while in the EDOU) were significantly
      associated with admission to hospital. CONCLUSIONS: Variables exist that predict
      a 'failed' short stay admission. These might be used to identify patients less
      suitable for admission to the EDOU and better suited to admission directly under
      a hospital team.

PMID- 18062782
TI  - Australasian emergency physicians: a learning and educational needs analysis.
      Part five: barriers to CPD experienced by FACEM, and attitudes to the ACEM MOPS
      programme.
AB  - OBJECT: To determine the barriers to continuous professional development (CPD)
      perceived by Fellows of the Australasian College for Emergency Medicine (FACEM),
      their opinions on the maintenance of professional standards programme (MOPS), and
      other aspects of education. METHOD: Mailed survey offering 12 factors that could
      prevent them from participating in CPD. FACEM were asked to rate the items on
      Likert from 1, no barrier, through to 5, insurmountable barrier. Qualitative
      comments on barriers, MOPS and other education were grouped. RESULTS: Nearly 47%
      of FACEM nominated lack of time with too many other priorities as significant of
      insurmountable barriers to CPD whilst 41% cited their ED as being too busy to
      leave and 35% had family commitments preventing CPD. While commitments,
      resistance from colleagues or employers (7%), lack of personal motivation or
      interest, (7.5%) lack of conference leave (8%) or financial restraint (14.5%)
      were lesser barriers for FACEM. Scheduling at inconvenient times (25%) and
      geographical factors (19%) were also perceived as significant barriers. Analysis
      of qualitative responses highlighted staff shortages, family reasons, personal
      fatigue, lack of interest in available CPD, cost and limited nonclinical time as
      being important barriers for some FACEM. Less than 50% of FACEM agreed that
      current allocation of MOPS points was appropriate or that the website spot
      diagnoses and scenarios kept their knowledge current. Nearly 28% did not find
      online MOPS easy to comprehend. CONCLUSION: These findings may assist in
      facilitating increased participation in CPD by FACEM.

PMID- 18062783
TI  - Australasian emergency physicians: a learning and educational needs analysis.
      Part Four: CPD topics desired by emergency physicians.
AB  - OBJECTIVE: To report the preferences of Fellows of the Australasian College for
      Emergency Medicine for topics they would desire for their continuing professional
      development (CPD). METHOD: A mailed survey of Fellows of the Australasian College
      for Emergency Medicine asked for Likert type responses on the desirability of CPD
      on 15 procedural skills, 13 management skills, 11 clinical emergency topics, 9
      topics related to teaching, 7 related to diagnostics and 5 evidence based
      practice topics. RESULTS: CPD in procedural skills of advanced and surgical
      airways, ED ultrasound, ventilation, skills, plastic procedures and regional
      anaesthesia were nominated as desirable by 85% of emergency physicians (EP). More
      than 90% desired CPD in ophthalmological, otorhinolaryngeal, neonatal and
      paediatric emergencies. Of diagnostic skills, more than 80% considered CPD on
      computerized tomography, electrocardiography and plain X-ray interpretation as
      desirable, well as CPD about teaching in general, simulation and preparing
      candidates for fellowship exams. Of the 12 management skills, 11 were seen as
      desirable topics by more than 70%, with counter disaster planning, giving
      feedback and dealing with complaints the most popular. All evidence based
      practice related skills, including interpreting statistics and undertaking
      literature searches were seen as desirable topics by more than 80% of EP.
      CONCLUSION: This information may assist in the planning of future educational
      interventions for emergency physicians. EP seek CPD on management, educational
      and other non clinical skills, as well as topics relating directly to patient
      care.

PMID- 18062784
TI  - Electronic interface for emergency department management of asthma: a randomized
      control trial of clinician performance.
AB  - OBJECTIVES: To evaluate the effectiveness of an integrated and dynamic electronic
      decision support system for management of acute asthma in the ED. METHODS: A
      randomized trial was conducted comparing clinician performance using this
      electronic interface compared with paper documentation in a simulation scenario.
      The outcomes were documentation of asthma-related information and consultation
      times. RESULTS: Use of this electronic interface was associated with
      significantly higher rates of documentation in 7 out of 10 variables, including
      provision of written short-term asthma management plans. After adjustment for
      participant seniority, there was no significant difference in consultation times.
      CONCLUSION: In a simulation trial, use of this electronic interface was
      associated with improvements in clinical and discharge documentation. Further
      studies are required to test this prototype in clinical practice.

PMID- 18062785
TI  - How fast is the focused assessment with sonography for trauma examination
      learning curve?
AB  - OBJECTIVE: Although accuracy for focused assessment with sonography for trauma
      (FAST) examination interpretation has been widely reported, the learning curve
      for FAST interpretation by emergency medicine (EM) residents who are novice to
      ultrasound has not been well described. The present study's objective was to
      analyse EM resident FAST interpretation accuracy over 18 months. METHODS:
      Prospective comparison of EM resident FAST interpretation accuracy for a class of
      nine EM residents at baseline after initial training, and then every 6 months
      over 18 months. Accuracy was scored after viewing the same 20 video clip images
      of the four anatomic views for five FAST examination cases. Three video clips had
      large anechoic stripe (AS) (>6 mm), four had moderate AS (6 mm > or = AS > or = 3
      mm), two had small AS (<3 mm), and eleven had no AS (AS = 0 mm). A surgeon with
      20 years of ultrasound experience confirmed the video clip interpretations. Data
      analysis used descriptive statistics with 95% confidence intervals. RESULTS: For
      no AS views, EM resident accuracy was 79.8% (70.3-86.9%) baseline, 91.9% (84.2
      96.2%) at 12 months, and 92.9% (85.5-96.9%) at 18 months. For small AS views,
      resident accuracy was 27.8% (10.7-53.6%) baseline, 66.7% (41.2-85.7%) at 12
      months, and 72.2% (46.4-89.3%) at 18 months. For large AS views, resident
      accuracy was 77.8% (57.3-90.6%) baseline, 86.1% (69.7-94.8%) at 12 months, and
      100.0% (84.5-100%) at 18 months. CONCLUSION: Over 18 months, EM resident FAST
      interpretation accuracy steadily increased. By 12 months (or 35 examinations),
      the accuracy of EM residents novice to ultrasound approximated previously
      reported accuracy rates.

PMID- 18062786
TI  - Australasian emergency physicians: a learning and educational needs analysis.
      Part three: participation by FACEM in available CPD: what do they do and do they
      like it?
AB  - OBJECTIVE: To determine the participation of Emergency Physicians (EP) in
      currently available continuing professional development opportunities (CPD),
      their perception of the usefulness of available CPD and their preferred format or
      method of CPD desired in the future. METHOD: A mailed survey of Fellows of the
      Australasian College for Emergency Medicine with 17 Likert type options on
      educational methods and qualitative analysis grouping volunteered free text
      responses. RESULTS: The most frequent learning methods reported by EP are on the
      job contact with other clinicians, formal ED based teaching and reading journals,
      which were also perceived as useful or very useful learning methods by more than
      90% of EP. Less than 15% often or always participate on hospital grand rounds,
      high fidelity simulation, computer programmes or commercially sponsored events.
      Increased exposure was desired to high-fidelity simulation center skills training
      by 58% of respondents with nearly 49% of fellows also wanting more participation
      in international conferences with around 44% of fellows also wanting more
      participation in international conferences with around 44% desiring more formal
      teaching in the ED, more formal feedback on performance, and more meetings with
      other hospital departments. Over 50% of EP want less or no exposure to
      commercially sponsored dinners or events. CONCLUSION: Whilst emergency physicians
      currently participate in a wide variety of learning methods, the results of this
      survey suggest EP most appreciate ED based teaching, would like more contact with
      other departments, along with increased opportunities for simulation based
      learning and attendance at international conferences.

PMID- 18062787
TI  - Australasian emergency physicians: a learning and educational needs analysis.
      Part two: confidence of FACEM for tasks and skills.
AB  - OBJECTIVE: To determine the degree of confidence perceived by Fellows of the
      Australasian College for Emergency Medicine for a variety of procedural, patient
      management, educational and research skills, and tasks that may be required of
      them. METHOD: Mailed survey with Likert scales and grouped qualitative responses.
      RESULTS: More than 90% of emergency physicians (EP) feel usually or always
      confident of their skills for peripheral vascular access, procedural sedation,
      fluid resuscitation, tube thoracostomy, managing patients with altered conscious
      state, cardiac emergencies, behavioural disturbance, and interpreting acid base
      and other blood tests. Less than 50% felt confident performing surgical airways,
      ED ultrasound, managing neonatal emergencies or interpreting MRI. Of non-clinical
      skills, while most EP were confident of their ability to write references,
      debrief staff, lead group tutorials and prepare slides, a minority felt usually
      or always confident about budgeting and finance, preparing submissions, dealing
      with the media, appearing in court or marking examination papers. Whilst nearly
      75% were confident about the information technology skills required of them for
      clinical practice, less than 25% of EP felt confident about conducting research
      and less than 15% were confident applying or interpreting statistics. CONCLUSION:
      This information may assist in the planning of future educational interventions
      for EP.

PMID- 18062788
TI  - Australasian emergency physicians: a learning and educational needs analysis.
      Part one: background and methodology. Profile of FACEM.
AB  - OBJECTIVE: Fellows of the Australasian College for Emergency Medicine (FACEM)
      have opportunities to participate in a range of continuing professional
      development activities. To inform FACEM and assist those involved in planning
      continuing professional development interventions for FACEM, we undertook a
      learning needs analysis of emergency physicians. METHOD: Exploratory study using
      survey methodology. Following questionnaire development by iterative feedback
      with emergency physicians and researchers, a mailed survey was distributed to all
      FACEM. The survey comprised eight items on work and demographic characteristics
      of FACEM, and 194 items on attitudes to existing learning opportunities, barriers
      to learning, and perceived learning needs and preferences. RESULTS: Fifty-eight
      percent (503/854) of all FACEM surveyed responded to the questionnaire, almost
      half of whom attained their FACEM after year 2000. The sample comprised mostly
      males (72.8%) with mean age of the sample 41.6 years, similar to ACEM database.
      Most respondents reported working in ACEM accredited hospitals (89%), major
      referral hospitals (54%), and practiced on both children and adults (78%). FACEM
      reported working on average 26.7 clinical hours per week with those at private
      hospitals working a greater proportion of clinical hours than other hospital
      types. CONCLUSION: As the first of six related reports, this paper documents the
      methodology used, including questionnaire development, and provides the
      demographics of responding FACEM, including the clinical and non-clinical hours
      worked and type of hospital of principal employment.

PMID- 18062789
TI  - Handover from paramedics: observations and emergency department clinician
      perceptions.
AB  - OBJECTIVES: 1. To evaluate emergency clinician attitudes towards handover from
      prehospital paramedics. 2. To determine the content and methods of paramedic
      handover delivery to emergency clinicians. METHODS: Exploratory study comprising
      questionnaire of emergency clinicians and observation of paramedic-to-emergency
      clinician handover with associated survey at an adult tertiary referral hospital
      with approximately 12,000 ambulance arrivals of 37,000 annual attendances.
      RESULTS: Emergency staff found handover from paramedics on patient conditions
      relevant, especially for altered consciousness (94%, 95% CI 83.5-98.6), trauma
      (90%, 95% CI 82.0-98.4) and chest pain (88%, 95% CI 79.0-97.0), but less so for
      behavioural disturbance (67%, 95% CI 53.7-79.5). A total of 621 handovers from
      311 ambulance arrivals were observed. Most arrivals (81%, 95% CI 76.4-85.4) were
      not preceded by prehospital communication. Paramedics handed over twice 91% of
      the time (95% CI 88.2-94.4). Doctors received direct paramedic handover for 12%
      (95% CI 8.0-15.1) of ambulance arrivals, including 19 team handovers, whereas
      triage nurses took 97% (95% CI 95.6-99.2) and attending nurses, 91% (95% CI 87.5
      93.9). Fifty per cent (95% CI 42.7-57.3) of emergency clinicians referred to
      ambulance sheets. Handover information was perceived to be useful and accurate in
      more than 80% of instances. Verbal handover occurred before ambulance sheet
      completion for 78% (95% CI 73.5-82.7). CONCLUSION: Although there is satisfaction
      in paramedic handover, prehospital notification and emergency physician contact
      with paramedics is uncommon for low acuity patients, who constitute the majority
      of ambulance attendances and hospital admissions. Scope for improved direct
      doctor-paramedic communication exists.

PMID- 18062790
TI  - Marginal donor grafts in heart transplantation: lessons learned from 25 years of
      experience.
AB  - Heart transplantation represents an established procedure in end-stage heart
      failure patients and results in satisfying long-term results. However, this
      surgical therapy is continuously limited by severe and progredient donor organ
      shortage in the last years. Therefore, adequate and optimal utilization of all
      suitable donor organs is mandatory to increase graft availability. Evidence
      exists that certain 'standard' donor criteria can be significantly liberalized to
      increase the available donor pool by accepting 'Marginal Donors' who would, under
      conventional transplant guidelines, be declined as potential organ donors. The
      aim of this study was to review the available literature with regard to
      definitions and experiences with 'marginal' donor hearts and to discuss
      critically the controversies of numerous entities of donor criteria, which might
      be successfully liberalized. This review is thought to give an up-to-date
      overview of a modern concept of cardiac allograft acceptance based on a 25-year
      experience with heart transplantation.

PMID- 18062791
TI  - Mortality rates in patients with Barrett's oesophagus.
AB  - BACKGROUND: Patients with Barrett's oesophagus are at increased risk of
      oesophageal adenocarcinoma. Observational studies have suggested increase in
      overall mortality also but data are conflicting. AIM: To assess the cause of
      death in patients with Barrett's oesophagus compared with the general population.
      METHODS: Patients with Barrett's oesophagus were identified retrospectively in
      four hospitals in Leicestershire, UK using electronic endoscopy and
      histopathology records from 1997 to 2003. Data on deaths from this cohort of
      patients were identified through the Office of National Statistics and compared
      with age- and gender-adjusted mortality in the Leicestershire region. RESULT: In
      all, 1272 Barrett's patients were identified with 245 deaths in this cohort.
      Overall mortality was found to be increased [male standardized mortality ratio
      (SMR) = 552, 95% CI = 466-638; female SMR 455, 95% CI = 357-552]. The main
      disease areas that were responsible for this increase were oesophageal
      adenocarcinoma (n = 25, male SMR = 2171, 95% CI = 991-3351; female SMR = 1300,
      95% CI = 26-2574), bronchopneumonia (n = 70, male SMR = 146, 95% CI = 55-236;
      female SMR = 436, 95% CI = 272-601) and ischaemic heart disease (n = 51, male SMR
      = 186, 95% CI = 97-2748; female SMR = 205, 95% CI = 105-306). CONCLUSIONS:
      Patients with Barrett's oesophagus die more commonly of bronchopneumonia and
      ischaemic heart disease compared with oesophageal adenocarcinoma, and overall
      mortality in this group may be increased.

PMID- 18062792
TI  - Multiple-antigen immunization of chickens facilitates the generation of
      recombinant antibodies to autoantigens.
AB  - Antibody phage display is a powerful tool for the generation of monoclonal
      antibodies against virtually any given antigen. Chickens are phylogenetically
      more distant from humans compared to other laboratory animals, such as mice and
      rats. Therefore, the use of chickens is especially beneficial when generating
      recombinant antibodies against human autoantigens, which are often highly
      conserved among mammals. Another advantage of using chickens in antibody phage
      display is that the preparation of single chain variable fragment (scFv) antibody
      libraries is faster and easier compared to preparing such libraries from other
      species, as only two primer sets are needed for amplification of the chicken
      variable heavy chain (V(H)) and variable light chain (V(L)) genes. In the present
      study we explored the possibility to immunize chickens with antigen cocktails for
      the generation of recombinant antibody fragments directed to a range of human
      autoantigens. Two pairs of chickens were immunized with two cocktails of seven
      recombinant autoantigenic proteins, libraries were prepared and panned on the
      individual proteins. The polyclonal chicken sera reacted strongly with most of
      the antigens used for immunization. By creating and screening single-chain
      variable fragment antibody phage display libraries, recombinant monoclonal
      antibody fragments were isolated successfully against the autoantigens annexin
      XI, centromere protein B, heat shock protein B3, DNA topoisomerase I, histidyl
      tRNA synthetase, Ro52, Ro60, Rpp30 and U1A. In conclusion, the immunization of
      only four chickens with two distinct pools of a total of 14 autoantigenic
      proteins allowed the isolation of scFvs against nine of these antigens.

PMID- 18062793
TI  - Lipopolysaccharide augments the in vivo lethal action of doxorubicin against mice
      via hepatic damage.
AB  - The effect of lipopolysaccharide (LPS) on the in vivo lethal action of
      doxorubicin (DOX) against mice was studied. DOX killed LPS-pretreated mice much
      earlier than untreated mice, and exhibited a stronger toxic action against LPS
      pretreated mice. DOX-induced lethality in LPS-pretreated mice was due to severe
      hepatic damage, but there were no significant lesions in the heart, kidney and
      lung. Hepatic lesions were accompanied by caspase 3-positive cells and fragmented
      DNA-positive cells, suggesting the involvement of apoptosis. DOX induced the
      production of a high level of interferon (IFN)-gamma and tumour necrosis factor
      (TNF)-alpha in LPS-pretreated mice, but not in non-treated mice. The DOX-induced
      lethality was prevented significantly by anti-IFN-gamma antibody, but not anti
      TNF-alpha antibody. Administration of recombinant IFN-gamma in place of LPS
      augmented definitively the DOX-induced lethality. LPS augmented the DOX-induced
      lethality in TNF-alpha-deficient mice. Taken together, LPS was suggested to
      enhance DOX-induced IFN-gamma production and augment the in vivo lethal action
      via hepatic damage.

PMID- 18062794
TI  - Human T cells stimulate fibroblast-mediated degradation of extracellular matrix
      in vitro.
AB  - Several chronic diseases are characterized by inflammation, T cell recruitment
      and tissue remodelling. We hypothesized that activated T cells may stimulate
      remodelling of extracellular matrix (ECM) in vitro. Total T cells (CD3+) as well
      as CD4+ and CD8+ subsets were isolated from peripheral blood and stimulated,
      after which conditioned media (CM) were obtained. CM was added to human lung
      fibroblasts in three-dimensional collagen gels and the area of gels was measured
      daily. Hydroxyproline was determined as a measure of collagen degradation in the
      gels. Matrix metalloproteinase (MMP) activity in the culture media was analysed
      by gelatine zymography. Cytokine secretion of stimulated CD4+ and CD8+ T cells
      was analysed. CD3+ CM augmented collagen gel contraction in a time- and dose
      dependent manner (P < 0.0001). CD4+ T cell CM was more potent than CD8+ T cell CM
      (P < 0.001). CD3+ CM and CD4+ T cell CM, but not CD8+ T cell CM, stimulated
      fibroblast-mediated collagen degradation and MMP-9 activity. A broad-spectrum MMP
      inhibitor added to the culture system inhibited both gel contraction and MMP
      activity. Activated CD4+ T cells secreted significantly more tumour necrosis
      factor (TNF) and interleukin (IL)-6 compared to CD8+ T cells. CD3+ CM from
      patients with chronic obstructive pulmonary disease stimulated fibroblast
      mediated collagen gel contraction to the same magnitude as CD3+ CM from healthy
      controls. In conclusion, activated CD4+ T cells can stimulate fibroblast-mediated
      degradation of ECM in vitro. This could be a mechanism by which activated T cells
      stimulate degradation of lung tissue leading to pulmonary emphysema.

PMID- 18062795
TI  - Association of TNF polymorphisms with sarcoidosis, its prognosis and tumour
      necrosis factor (TNF)-alpha levels in Asian Indians.
AB  - Tumour necrosis factor (TNF)-alpha, an important proinflammatory cytokine, has
      been implicated in the pathogenesis of sarcoidosis, a multi-systemic
      granulomatous disorder of unknown aetiology. Here, we report for the first time
      the association of TNF haplotypes and genotypes with sarcoidosis and its
      prognosis in the Indian population. Five potentially functional promoter
      polymorphisms in the TNFA gene and a LTA_NcoI polymorphism (+252 position) of the
      LTA gene were genotyped in a clinically well-defined cohort of North-Indian
      patients with sarcoidosis (n = 96) and their regional controls (n = 155). Serum
      TNF-alpha (sTNF-alpha) and serum angiotensin converting enzyme (SACE) levels were
      measured and correlated with genotypes and haplotypes. The TNFA_-1031 and TNFA_
      863 polymorphisms were identified as markers for disease onset (FET P = 0.006 and
      0.042 for TNFA_-1031 and TNFA_-863, respectively). Additionally, the allele A of
      LTA_NcoI polymorphism was shown to be prevalent in the 'no treatment' group (FET
      P = 0.005), while the G allele was associated with frequent relapses on drug
      withdrawal (P = 0.057). Furthermore, the TNFA-308G>A and the TNFA-238G>A
      polymorphisms were found to influence sTNF-alpha (P = 0.054 and 0.0005,
      respectively) and SACE levels (P = 0.0017 and 0.056, respectively). The haplotype
      frequencies were significantly different in the patients and the controls (P =
      0.0067). The haplotype GTCCGG was identified as the major risk/susceptibility
      haplotype (P = 0.003) and was associated with increased SACE levels in the
      patient population. In conclusion, our study suggests an association of TNF
      polymorphisms with sarcoidosis.

PMID- 18062796
TI  - Persistent of respiratory syncytial virus in human dendritic cells and influence
      of nitric oxide.
AB  - The annual epidemics of respiratory syncytial virus (RSV) infection are probably
      explained by poor herd immunity and the existence of a dormant reservoir of virus
      that is activated by an unknown trigger. The virus causes particular problems in
      infants, the elderly and patients with chronic obstructive airways disease
      (COPD). During two consecutive winters, human monocyte-derived dendritic cells
      (DCs) were exposed on a single occasion to one of two forms of RSV labelled with
      a fluorescent expresser genes (rgRSV or rrRSV) during the epidemic season. The
      cultures were maintained for many months, with fresh DCs being added at monthly
      intervals. The cultures were variously exposed to 600 parts per billion (ppb)
      nitric oxide for 15 min, nitric oxide (NO) donors and NO inhibitors outside the
      RSV epidemic season. The pattern of productive infection of DCs in vitro appeared
      to parallel the natural epidemics, in that DCs exhibited evidence of viral
      replication and productive infection only as manifested by intracellular
      fluorescence and infection of HeLa cells during the RSV epidemic season. When the
      long-term cultures were exposed to the above agents outside the RSV epidemic
      season there was again evidence of vigorous replication and productive infection,
      as shown by the reappearance of fluorescence and productive infection of HeLa
      cells. The results indicate that RSV may remain dormant in dendritic cells for
      prolonged periods and that replication appears to be activated by suppression of
      endogenous NO production. These observations may be key to our understanding of
      the mechanisms contributing to the annual epidemics of RSV infection.

PMID- 18062797
TI  - The pyrimidin analogue cyclopentenyl cytosine induces alloantigen-specific non
      responsiveness of human T lymphocytes.
AB  - Cyclopentenyl cytosine (CPEC) has been shown to induce apoptosis in human T
      lymphoblastic cell lines and T cells from leukaemia patients. In this study we
      have addressed the question of whether CPEC is able to decrease proliferation and
      effector functions of human alloresponsive T lymphocytes and induce T cell
      anergy. The proliferative capacity of human peripheral blood mononuclear cells in
      response to allogeneic stimulation was measured by 5,6-carboxy-succinimidyl
      diacetate-fluorescein-ester staining. Flow cytometric analysis was performed
      using surface CD4, CD8, CD25, CD103 and intracellular perforin, granzyme A,
      granzyme B, caspase-3 and forkhead box P3 (FoxP3) markers. The in vivo
      immunosuppressive capacity was tested in a murine skin graft model. Addition of
      CPEC at a concentration of 20 nM strongly decreased the expansion and
      cytotoxicity of alloreactive T cells. Specific restimulation in the absence of
      CPEC showed that the cells became anergic. The drug induced caspase-dependent
      apoptosis of alloreactive T lymphocytes. Finally, CPEC increased the percentage
      of CD25(high) FoxP3+ CD4+ and CD103+ CD8+ T cells, and potentiated the effect of
      rapamycin in increasing the numbers of alloreactive regulatory T cells. Treatment
      with CPEC of CBA/CA mice transplanted with B10/Br skin grafts significantly
      prolonged graft survival. We conclude that CPEC inhibits proliferation and
      cytotoxicity of human alloreactive T cells and induces alloantigen non
      responsiveness in vitro.

PMID- 18062798
TI  - Immunoregulatory factors in multiple sclerosis patients during and after
      pregnancy: relevance of natural killer cells.
AB  - Multiple sclerosis (MS) ameliorates typically during pregnancy but after the
      delivery the relapse rate often increases. Our study was conducted to understand
      the immunoregulatory mechanisms accompanying this phenomenon. MS patients were
      followed-up prospectively during pregnancy and 6 months postpartum, with
      immunological characterization of the peripheral blood. Groups of age- and parity
      matched healthy pregnant women, and age- and sex-matched non-pregnant women and
      non-pregnant MS patients were studied as controls. In our patient cohort, the
      annualized relapse rate was 1.0 +/- 1.0 relapses/woman/year (mean +/- standard
      deviation) during the year before pregnancy, but dropped to 0.2 +/- 0.9 during
      the third trimester (P = 0.02). After the delivery the relapse rate increased
      again to 1.4 +/- 1.9 (1-3 months postpartum versus third trimester P = 0.003).
      While percentages of peripheral blood CD3, CD4, CD8 and CD19 immune cell subsets
      were unchanged over the observation period, reduced disease activity during the
      last trimester was associated with a significant increase in the percentage of
      circulating CD56(bright) natural killer (NK) cells. Simultaneously, the
      proportion of circulating CD56(dim) NK cells was clearly reduced. No alteration
      was noted in CD4+ CD25(high) forkhead box P3+ regulatory T cells. Production of
      interferon-gamma by peripheral blood lymphocytes was down-regulated significantly
      during pregnancy in comparison to the postpartum period, resulting in an
      increased T helper type 2 (Th2) : Th1 ratio during pregnancy. In conclusion,
      pregnant state in MS patients is characterized by an increase in the percentage
      of CD56(bright) NK cells and by enhanced Th2 type cytokine secretion. Our
      findings suggest a potential role for CD56(bright) regulatory NK cells in the
      control of autoimmune inflammation during pregnancy in MS.

PMID- 18062799
TI  - Long-term interleukin-10 presence induces the development of a novel, monocyte
      derived cell type.
AB  - Interleukin (IL)-10 is one of the most crucial immunoregulatory cytokines. Its
      short-term effects have been analysed extensively, but little is known about its
      long-term effects. This is of considerable importance, as high systemic IL-10
      levels are present for long periods in patients with persistent viral infections,
      certain cancers and in critical care patients. Our study investigated the effects
      of the long-term presence of IL-10 on human peripheral blood monocytes. In vitro,
      IL-10 treatment of these cells for 7 days induced the development of a novel cell
      type characterized by unique phenotypical and functional characteristics. These
      cells showed high HLA-DR expression and low expression of CD86 and other co
      stimulatory molecules on their surface. The mRNA levels of both HLA-DR and CD86
      were high, but no intracellular accumulation of CD86 protein was observed. With
      respect to its function, these cells showed strongly diminished tumour necrosis
      factor-alpha production following lipopolysaccharide stimulation, strongly
      diminished allogenic CD4(+) T cell stimulatory capacity, and even induced a
      hyporesponsive state in CD4(+) T cells. The phenotype remained stable despite the
      removal of IL-10. In vivo, we found monocytic cells from patients exhibiting this
      phenotype after long-term IL-10 exposure. These results complement our knowledge
      further about the biological effects of IL-10 and may provide an explanation for
      the sustained immunodeficiency in cases of the persistent presence of systemic IL
      10.

PMID- 18062800
TI  - Maternal and neonatal lipopolysaccharide and Fas responses are altered by
      antenatal risk factors for sepsis.
AB  - The diagnosis of neonatal sepsis is difficult, resulting in unnecessary treatment
      to minimize morbidity and mortality. We hypothesized that exposure to antenatal
      risk factors for sepsis alters the perinatal neutrophil phenotype. The study
      setting was a tertiary referral university-affiliated maternity and neonatal
      hospital. Neutrophils from adults, normal neonates, neonates with antenatal
      sepsis risk factors and their respective maternal samples were incubated alone,
      with agonistic Fas antibody or with lipopolysaccharide (LPS). Surface receptor
      CD11b expression and the percentage apoptosis (persistent inflammatory response)
      were assessed using flow cytometry. Both mothers and asymptomatic neonates
      exposed to maternal sepsis risk factors had increased spontaneous neutrophil
      apoptosis compared to their respective controls. Infants with sepsis were LPS and
      Fas hyporesponsive. Maternal neutrophils had a delay in apoptosis in all groups
      with enhanced LPS and Fas responses associated with neonatal sepsis. CD11b
      expression was not altered significantly between groups. Maternal neutrophil
      function is altered in neonatal sepsis and may have a diagnostic role. Neonatal
      sepsis was associated with LPS hyporesponsiveness, potentially increasing
      susceptibility to infection.

PMID- 18062801
TI  - Chronic unexplained anaemia in isolated autoimmune thyroid disease or associated
      with autoimmune related disorders.
AB  - OBJECTIVE: The prevalence of chronic unexplained anaemia was analysed in patients
      with autoimmune thyroid disease (ATD). DESIGN: The presence of chronic
      unexplained anaemia, defined as anaemia not related to evident or occult bleeding
      and/or to erythropoietic disorders, was retrospectively assessed and compared in
      patients with nonautoimmune thyroid disease (NATD) and in patients with ATD.
      SUBJECTS AND MEASUREMENTS: Biochemical and morphological parameters of anaemia
      were investigated and characterized in 1643 consecutive Caucasian outpatients
      with thyroid disease. In 991 patients, thyroid disease had a nonautoimmune
      origin. ATD was diagnosed in 652 patients (71 had Graves' disease and 581 had
      Hashimoto's thyroiditis and its variants). In 145 patients ATD was associated
      with other autoimmune disorders. RESULTS: The presence of chronic unexplained
      anaemia was diagnosed in 123 patients (7.5%). Forty-eight had a thalassaemic
      trait, representing 2.9% of the whole sample. A true chronic unexplained anaemia
      was recorded in 75/1643 (4.6%). The occurrence of unexplained anaemia was similar
      in patients with NATD (1.9%) and in those with isolated ATD (2.96%; P = NS) but
      increased in patients with ATD and autoimmune related disorders (ARD) compared to
      patients with isolated ATD and/or with NATD (28.3%; both P < 0.0001; RR = 9.56
      and 14.75, respectively). Chronic unexplained anaemia was virtually absent in
      hyperthyroid patients and was more prevalent in hypothyroid than in euthyroid
      patients with ATD (P = 0.0047; RR = 2.104). CONCLUSIONS: These results indicate
      that the increased frequency of chronic anaemia in patients with ATD is
      essentially due to the presence of concomitant autoimmune gastrointestinal
      diseases.

PMID- 18062802
TI  - Familial prevalence and age of RET germline mutations: implications for
      screening.
AB  - OBJECTIVE: No comprehensive information exists nationwide about the familial
      prevalence and age of rearranged during transfection (RET) germline mutations.
      The current investigation was undertaken to provide such natural history data
      which are urgently needed to enable factual decision-making about DNA-based
      screening programmes for RET germline mutations. DESIGN: Descriptive study drawn
      on countrywide referrals to a specialist surgical centre. PATIENTS: Included were
      452 patients from 141 German RET families: 277 carriers referred for pre-emptive
      or therapeutic surgery, and 175 additional carriers or relatives with endocrine
      tumours associated with multiple endocrine neoplasia type 2 (MEN2). MEASUREMENTS:
      Key variables included familial prevalence, phenotype and latest year of birth of
      RET germline mutations. RESULTS A total of 26 different RET germline mutations
      were identified among the 141 RET families: C634R (21%); M918T (15%); C634Y (9%);
      L790F/TTG-->TTT (8%), Y791F (7%), V804M (6%); C620R and C634F (5% each);
      L790F/TTG-->TTC and C634S/TGC-->TCC (4% each); C618S/TGC-->AGC, C634G and S891A
      (2% each); C618F and E768D (1% each); and in < 1% each: C609G, C611F, C611Y,
      C618G, C618Y, C620S/TGC-->AGC, C620S/TGC-->TCC, C620Y, C630R, D631Y and V804L.
      Most of these differences in prevalence rates, seemingly, were caused by recent
      spontaneous mutations in the germline. With rare exceptions, longstanding
      transmission was noted in at least one RET family per affected codon. Many
      germline mutations were traceable back to the early 20th, and a few even to the
      19th century. CONCLUSIONS: These data reveal the potential of DNA-based screening
      of all relevant RET exons, especially for index patients with solitary, seemingly
      sporadic disease.

PMID- 18062803
TI  - No hypoperfusion is produced in the epicardium during application of myocardial
      topical negative pressure in a porcine model.
AB  - BACKGROUND: Topical negative pressure (TNP), commonly used in wound therapy, has
      been shown to increase blood flow and stimulate angiogenesis in skeletal muscle.
      We have previously shown that a myocardial TNP of -50 mmHg significantly
      increases microvascular blood flow in the myocardium. When TPN is used in wound
      therapy (on skeletal and subcutaneous tissue) a zone of relative hypoperfusion is
      seen close to the wound edge. Hypoperfusion induced by TNP is thought to depend
      on tissue density, distance from the negative pressure source, and the amount
      negative pressure applied. When applying TNP to the myocardium, a significant,
      long-standing zone of hypoperfusion could theoretically cause ischemia, and
      negative effects on the myocardium. The current study was designed to elucidate
      whether hypoperfusion was produced during myocardial TNP. METHODS: Six pigs
      underwent median sternotomy. Laser Doppler probes were inserted horizontally into
      the heart muscle in the LAD area, at depths of approximately, 1-2 mm. The
      microvascular blood flow was measured before and after the application of a TNP.
      Analyses were performed before left anterior descending artery (LAD) occlusion
      (normal myocardium) and after 20 minutes of LAD occlusion (ischemic myocardium).
      RESULTS: A TNP of -50 mmHg induced a significant increase in microvascular blood
      flow in normal myocardium (**p = 0.01), while -125 mmHg did not significantly
      alter the microvascular blood flow. In ischemic myocardium a TNP of -50 mmHg
      induced a significant increase in microvascular blood flow (*p = 0.04), while 
      125 mmHg did not significantly alter the microvascular blood flow. CONCLUSION: No
      hypoperfusion could be observed in the epicardium in neither normal nor ischemic
      myocardium during myocardial TNP.

PMID- 18062804
TI  - Features of asthma management: quantifying the patient perspective.
AB  - BACKGROUND: In the management of asthma, features of care important to patients
      may not be fully appreciated. This study quantifies the importance of different
      features of asthma management from the patient perspective. This may assist in
      the development of personalised management strategies. METHODS: We used the
      technique of discrete choice experiment (DCE). Patients over 18 years of age with
      asthma, prescribed and taking medicine at step 3 of the UK guidelines were
      recruited from 15 general (family) practices in three areas of the UK. 147
      evaluable questionnaires were returned from a total of 348 sent out. The outcome
      measures were the relative importance to patients of features of asthma
      management and the impact of changes in asthma management, as measured by utility
      shift between the features tested. RESULTS: The largest shift in mean utility
      values was recorded in "number of inhalers" and "use of inhaled steroid". Use of
      a personal asthma action plan was ranked next highest. CONCLUSION: This study
      suggests that adults with moderate or severe asthma would trade some improvements
      in symptom relief in favour of, for example, simpler treatment regimens that use
      as few inhalers as possible and a lower dose of inhaled steroid.

PMID- 18062805
TI  - A critical appraisal of guidelines for the management of knee osteoarthritis
      using Appraisal of Guidelines Research and Evaluation criteria.
AB  - Clinical practice guidelines have been elaborated to summarize evidence related
      to the management of knee osteoarthritis and to facilitate uptake of evidence
      based knowledge by clinicians. The objectives of the present review were
      summarizing the recommendations of existing guidelines on knee osteoarthritis,
      and assessing the quality of the guidelines using a standardized and validated
      instrument--the Appraisal of Guidelines Research and Evaluation (AGREE) tool.
      Internet medical literature databases from 2001 to 2006 were searched for
      guidelines, with six guidelines being identified. Thirteen clinician researchers
      participated in the review. Each reviewer was trained in the AGREE instrument.
      The guidelines were distributed to four groups of three or four reviewers, each
      group reviewing one guideline with the exception of one group that reviewed two
      guidelines. One independent evaluator reviewed all guidelines. All guidelines
      effectively addressed only a minority of AGREE domains. Clarity/presentation was
      effectively addressed in three out of six guidelines, scope/purpose and rigour of
      development in two guidelines, editorial independence in one guideline, and
      stakeholder involvement and applicability in none. The clinical management
      recommendation tended to be similar among guidelines, although interventions
      addressed varied. Acetaminophen was recommended for initial pain treatment,
      combined with exercise and education. Nonsteroidal anti-inflammatory drugs were
      recommended if acetaminophen failed to control pain, but cautiously because of
      gastrointestinal risks. Surgery was recommended in the presence of persistent
      pain and disability. Education and activity management interventions were
      superficially addressed in most guidelines. Guideline creators should use the
      AGREE criteria when developing guidelines. Innovative and effective methods of
      knowledge translation to health professionals are needed.

PMID- 18062807
TI  - Neck fracture of a cementless forged titanium alloy femoral stem following total
      hip arthroplasty: a case report and review of the literature.
AB  - INTRODUCTION: Fractures of the neck of the femoral component have been reported
      in uncemented total hip replacements, however, to our knowledge, no fractures of
      the neck of a cementless forged titanium alloy femoral stem coated in the
      proximal third with hydroxy-apatite have been reported in the medical literature.
      CASE PRESENTATION: This case report describes a fracture of the neck of a
      cementless forged titanium alloy stem coated in the proximal third with hydroxy
      apatite. CONCLUSION: The neck of the femoral stem failed from fatigue probably
      because of a combination of factors described analytically below.

PMID- 18062806
TI  - Gene expression analysis reveals early changes in several molecular pathways in
      cerebral malaria-susceptible mice versus cerebral malaria-resistant mice.
AB  - BACKGROUND: Microarray analyses allow the identification and assessment of
      molecular signatures in whole tissues undergoing pathological processes. To
      better understand cerebral malaria pathogenesis, we investigated intra-cerebral
      gene-expression profiles in well-defined genetically cerebral malaria-resistant
      (CM-R) and CM-susceptible (CM-S) mice, upon infection by Plasmodium berghei ANKA
      (PbA). We investigated mouse transcriptional responses at early and late stages
      of infection by use of cDNA microarrays. RESULTS: Through a rigorous statistical
      approach with multiple testing corrections, we showed that PbA significantly
      altered brain gene expression in CM-R (BALB/c), and in CM-S (CBA/J and C57BL/6)
      mice, and that 327 genes discriminated between early and late infection stages,
      between mouse strains, and between CM-R and CM-S mice. We further identified 104,
      56, 84 genes with significant differential expression between CM-R and CM-S mice
      on days 2, 5, and 7 respectively. The analysis of their functional annotation
      indicates that genes involved in metabolic energy pathways, the inflammatory
      response, and the neuroprotection/neurotoxicity balance play a major role in
      cerebral malaria pathogenesis. In addition, our data suggest that cerebral
      malaria and Alzheimer's disease may share some common mechanisms of pathogenesis,
      as illustrated by the accumulation of beta-amyloid proteins in brains of CM-S
      mice, but not of CM-R mice. CONCLUSION: Our microarray analysis highlighted
      marked changes in several molecular pathways in CM-S compared to CM-R mice,
      particularly at early stages of infection. This study revealed some promising
      areas for exploration that may both provide new insight into the knowledge of CM
      pathogenesis and the development of novel therapeutic strategies.

PMID- 18062808
TI  - Major surgery delegation to mid-level health practitioners in Mozambique: health
      professionals' perceptions.
AB  - BACKGROUND: This study examines the opinions of health professionals about the
      capacity and performance of the 'tecnico de cirurgia', a surgically trained
      assistant medical officer in the Mozambican health system. Particular attention
      is paid to the views of medical doctors and maternal and child health nurses.
      METHODS: The results are derived from a qualitative study using both semi
      structured interviews and group discussions. Health professionals (n=71) were
      interviewed at both facility and system level. Eight group discussion sessions of
      about two hours each were run in eight rural hospitals with a total of 48
      participants. Medical doctors and district officers were excluded from group
      discussion sessions due to their hierarchical position which could have prevented
      other workers from expressing opinions freely. RESULTS: Health workers at all
      levels voiced satisfaction with the work of the "tecnicos de cirurgia". They
      stressed the life-saving skills of these cadres, the advantages resulting from a
      reduction in the need for patient referrals and the considerable cost reduction
      for patients and their families. Important problems in the professional status
      and remuneration of "tecnicos de cirurgia" were identified. CONCLUSION: This
      study, the first one to scrutinize the judgements and attitudes of health workers
      towards the "tecnico de cirurgia", showed that, despite some shortcomings, this
      cadre is highly appreciated and that the health delivery system does not
      recognize and motivate them enough. The findings of this study can be used to
      direct efforts to improve motivation of health workers in general and of tecnicos
      de cirurgia in particular.

PMID- 18062810
TI  - Threshold-dominated regulation hides genetic variation in gene expression
      networks.
AB  - BACKGROUND: In dynamical models with feedback and sigmoidal response functions,
      some or all variables have thresholds around which they regulate themselves or
      other variables. A mathematical analysis has shown that when the dose-response
      functions approach binary or on/off responses, any variable with an equilibrium
      value close to one of its thresholds is very robust to parameter perturbations of
      a homeostatic state. We denote this threshold robustness. To check the empirical
      relevance of this phenomenon with response function steepnesses ranging from a
      near on/off response down to Michaelis-Menten conditions, we have performed a
      simulation study to investigate the degree of threshold robustness in models for
      a three-gene system with one downstream gene, using several logical input gates,
      but excluding models with positive feedback to avoid multistationarity. Varying
      parameter values representing functional genetic variation, we have analysed the
      coefficient of variation (CV) of the gene product concentrations in the stable
      state for the regulating genes in absolute terms and compared to the CV for the
      unregulating downstream gene. The sigmoidal or binary dose-response functions in
      these models can be considered as phenomenological models of the aggregated
      effects on protein or mRNA expression rates of all cellular reactions involved in
      gene expression. RESULTS: For all the models, threshold robustness increases with
      increasing response steepness. The CVs of the regulating genes are significantly
      smaller than for the unregulating gene, in particular for steep responses. The
      effect becomes less prominent as steepnesses approach Michaelis-Menten
      conditions. If the parameter perturbation shifts the equilibrium value too far
      away from threshold, the gene product is no longer an effective regulator and
      robustness is lost. Threshold robustness arises when a variable is an active
      regulator around its threshold, and this function is maintained by the feedback
      loop that the regulator necessarily takes part in and also is regulated by. In
      the present study all feedback loops are negative, and our results suggest that
      threshold robustness is maintained by negative feedback which necessarily exists
      in the homeostatic state. CONCLUSION: Threshold robustness of a variable can be
      seen as its ability to maintain an active regulation around its threshold in a
      homeostatic state despite external perturbations. The feedback loop that the
      system necessarily possesses in this state, ensures that the robust variable is
      itself regulated and kept close to its threshold. Our results suggest that
      threshold regulation is a generic phenomenon in feedback-regulated networks with
      sigmoidal response functions, at least when there is no positive feedback.
      Threshold robustness in gene regulatory networks illustrates that hidden genetic
      variation can be explained by systemic properties of the genotype-phenotype map.

PMID- 18062809
TI  - Expressed Sequence Tags from the oomycete Plasmopara halstedii, an obligate
      parasite of the sunflower.
AB  - BACKGROUND: Sunflower downy mildew is a major disease caused by the obligatory
      biotrophic oomycete Plasmopara halstedii. Little is known about the molecular
      mechanisms underlying its pathogenicity. In this study we used a genomics
      approach to gain a first insight into the transcriptome of P. halstedii. RESULTS:
      To identify genes from the obligatory biotrophic oomycete Plasmopara halstedii
      that are expressed during infection in sunflower (Helianthus annuus L.) we
      employed the suppression subtraction hybridization (SSH) method from sunflower
      seedlings infected by P. halstedii. Using this method and random sequencing of
      clones, a total of 602 expressed sequence tags (ESTs) corresponding to 230 unique
      sequence sets were identified. To determine the origin of the unisequences, PCR
      primers were designed to amplify these gene fragments from genomic DNA isolated
      either from P. halstedii sporangia or from Helianthus annuus. Only 145
      nonredundant ESTs which correspond to a total of 373 ESTs (67.7%) proved to be
      derived from P. halstedii genes and that are expressed during infection in
      sunflower. A set of 87 nonredundant sequences were identified as showing matches
      to sequences deposited in public databases. Nevertheless, about 7% of the ESTs
      seem to be unique to P. halstedii without any homolog in any public database.
      CONCLUSION: A summary of the assignment of nonredundant ESTs to functional
      categories as well as their relative abundance is listed and discussed.
      Annotation of the ESTs revealed a number of genes that could function in
      virulence. We provide a first glimpse into the gene content of P. halstedii.
      These resources should accelerate research on this important pathogen.

PMID- 18062811
TI  - Chlamydia pneumoniae aggravates vein graft intimal hyperplasia in a rat model.
AB  - BACKGROUND: Along with angioplasty, autologus vein grafts are commonly used for
      artery bypass grafting in patients with advanced arterial stenosis and drug
      resistant angina pectoris. Although initially a successful procedure, long-term
      functionality is limited due to proliferation and migration of smooth muscle
      cells. Like in atherosclerosis, common chronic infections caused by viruses and
      bacteria may contribute to this process of vein graft failure. Here we
      investigated the possible role of Chlamydia pneumoniae (Cpn) in the pathogenesis
      of venous graft failure in an experimental animal model. In 2 groups (n = 10
      rats/group), an epigastric vein-to-common femoral artery interposition graft was
      placed. Immediately thereafter, rats were infected with Cpn (5*108 IFU) or
      injected with control solutions. Rats were sacrificed three weeks after surgery
      and the grafts were harvested for morphometrical and immunohistochemical
      analysis. RESULTS: Cpn administration immediately after vein grafting resulted in
      a significant increase in medial cross-sectional area, wall thickness and total
      wall area. There were no significant differences in T-cell or macrophage influx.
      Likewise, although positive immunostaining for both HSP60 and CRP could be
      detected, no differences were found between groups. Based on the observation that
      the number of cells/microm2 was also not altered, we conclude that Cpn infection
      stimulates smooth muscle cell proliferation by hereunto unknown molecular
      mechanisms, resulting in a significant increase in intimal hyperplasia.
      CONCLUSION: In conclusion, in a well defined animal model we present here for the
      first time evidence for a role of Chlamydia pneumoniae in the process of venous
      graft failure.

PMID- 18062812
TI  - Characterization of a human coagulation factor Xa-binding site on Viperidae snake
      venom phospholipases A2 by affinity binding studies and molecular bioinformatics.
AB  - BACKGROUND: The snake venom group IIA secreted phospholipases A2 (SVPLA2),
      present in the Viperidae snake family exhibit a wide range of toxic and
      pharmacological effects. They exert their different functions by catalyzing the
      hydrolysis of phospholipids (PL) at the membrane/water interface and by highly
      specific direct binding to: (i) presynaptic membrane-bound or intracellular
      receptors; (ii) natural PLA2-inhibitors from snake serum; and (iii) coagulation
      factors present in human blood. RESULTS: Using surface plasmon resonance (SPR)
      protein-protein interaction measurements and an in vitro biological test of
      inhibition of prothrombinase activity, we identify a number of Viperidae venom
      SVPLA2s that inhibit blood coagulation through direct binding to human blood
      coagulation factor Xa (FXa) via a non-catalytic, PL-independent mechanism. We
      classify the SVPLA2s in four groups, depending on the strength of their binding.
      Molecular electrostatic potentials calculated at the surface of 3D homology
      modeling models show a correlation with inhibition of prothrombinase activity. In
      addition, molecular docking simulations between SVPLA2 and FXa guided by the
      experimental data identify the potential FXa binding site on the SVPLA2s. This
      site is composed of the following regions: helices A and B, the Ca2+ loop, the
      helix C-beta-wing loop, and the C-terminal fragment. Some of the SVPLA2 binding
      site residues belong also to the interfacial binding site (IBS). The interface in
      FXa involves both, the light and heavy chains. CONCLUSION: We have experimentally
      identified several strong FXa-binding SVPLA2s that disrupt the function of the
      coagulation cascade by interacting with FXa by the non-catalytic PL-independent
      mechanism. By theoretical methods we mapped the interaction sites on both, the
      SVPLA2s and FXa. Our findings may lead to the design of novel, non-competitive
      FXa inhibitors.

PMID- 18062813
TI  - The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary
      gland after neonatal/prepubertal exposure.
AB  - BACKGROUND: Phthalate esters like n-butyl benzyl phthalate (BBP) are widely used
      plasticizers. BBP has shown endocrine-disrupting properties, thus having a
      potential effect on hormone-sensitive tissues. The aim of this study is to
      determine the effect of neonatal/prepubertal exposure (post-natal days 2-20) to
      BBP on maturation parameters and on the morphology, proliferative index and
      genomic signature of the rat mammary gland at different ages of development (21,
      35, 50 and 100 days). RESULTS: Here we show that exposure to BBP increased the
      uterine weight/body weight ratio at 21 days and decreased the body weight at time
      of vaginal opening. BBP did not induce significant changes on the morphology of
      the mammary gland, but increased proliferative index in terminal end buds at 35
      days and in lobules 1 at several ages. Moreover, BBP had an effect on the genomic
      profile of the mammary gland mainly at the end of the exposure (21 days),
      becoming less prominent thereafter. By this age a significant number of genes
      related to proliferation and differentiation, communication and signal
      transduction were up-regulated in the glands of the exposed animals. CONCLUSION:
      These results suggest that BBP has an effect in the gene expression profile of
      the mammary gland.

PMID- 18062814
TI  - Measuring the functional sequence complexity of proteins.
AB  - BACKGROUND: Abel and Trevors have delineated three aspects of sequence
      complexity, Random Sequence Complexity (RSC), Ordered Sequence Complexity (OSC)
      and Functional Sequence Complexity (FSC) observed in biosequences such as
      proteins. In this paper, we provide a method to measure functional sequence
      complexity. METHODS AND RESULTS: We have extended Shannon uncertainty by
      incorporating the data variable with a functionality variable. The resulting
      measured unit, which we call Functional bit (Fit), is calculated from the
      sequence data jointly with the defined functionality variable. To demonstrate the
      relevance to functional bioinformatics, a method to measure functional sequence
      complexity was developed and applied to 35 protein families. Considerations were
      made in determining how the measure can be used to correlate functionality when
      relating to the whole molecule and sub-molecule. In the experiment, we show that
      when the proposed measure is applied to the aligned protein sequences of
      ubiquitin, 6 of the 7 highest value sites correlate with the binding domain.
      CONCLUSION: For future extensions, measures of functional bioinformatics may
      provide a means to evaluate potential evolving pathways from effects such as
      mutations, as well as analyzing the internal structural and functional
      relationships within the 3-D structure of proteins.

PMID- 18062815
TI  - Diversity and evolution of phycobilisomes in marine Synechococcus spp.: a
      comparative genomics study.
AB  - BACKGROUND: Marine Synechococcus owe their specific vivid color (ranging from
      blue-green to orange) to their large extrinsic antenna complexes called
      phycobilisomes, comprising a central allophycocyanin core and rods of variable
      phycobiliprotein composition. Three major pigment types can be defined depending
      on the major phycobiliprotein found in the rods (phycocyanin, phycoerythrin I or
      phycoerythrin II). Among strains containing both phycoerythrins I and II, four
      subtypes can be distinguished based on the ratio of the two chromophores bound to
      these phycobiliproteins. Genomes of eleven marine Synechococcus strains recently
      became available with one to four strains per pigment type or subtype, allowing
      an unprecedented comparative genomics study of genes involved in phycobilisome
      metabolism. RESULTS: By carefully comparing the Synechococcus genomes, we have
      retrieved candidate genes potentially required for the synthesis of
      phycobiliproteins in each pigment type. This includes linker polypeptides,
      phycobilin lyases and a number of novel genes of uncharacterized function.
      Interestingly, strains belonging to a given pigment type have similar
      phycobilisome gene complements and organization, independent of the core genome
      phylogeny (as assessed using concatenated ribosomal proteins). While phylogenetic
      trees based on concatenated allophycocyanin protein sequences are congruent with
      the latter, those based on phycocyanin and phycoerythrin notably differ and match
      the Synechococcus pigment types. CONCLUSION: We conclude that the phycobilisome
      core has likely evolved together with the core genome, while rods must have
      evolved independently, possibly by lateral transfer of phycobilisome rod genes or
      gene clusters between Synechococcus strains, either via viruses or by natural
      transformation, allowing rapid adaptation to a variety of light niches.

PMID- 18062816
TI  - Evolutionary history of bacteriophages with double-stranded DNA genomes.
AB  - BACKGROUND: Reconstruction of evolutionary history of bacteriophages is a
      difficult problem because of fast sequence drift and lack of omnipresent genes in
      phage genomes. Moreover, losses and recombinational exchanges of genes are so
      pervasive in phages that the plausibility of phylogenetic inference in phage
      kingdom has been questioned. RESULTS: We compiled the profiles of presence and
      absence of 803 orthologous genes in 158 completely sequenced phages with double
      stranded DNA genomes and used these gene content vectors to infer the
      evolutionary history of phages. There were 18 well-supported clades, mostly
      corresponding to accepted genera, but in some cases appearing to define new
      taxonomic groups. Conflicts between this phylogeny and trees constructed from
      sequence alignments of phage proteins were exploited to infer 294 specific acts
      of intergenome gene transfer. CONCLUSION: A notoriously reticulate evolutionary
      history of fast-evolving phages can be reconstructed in considerable detail by
      quantitative comparative genomics.

PMID- 18062817
TI  - Climate prediction of El Nino malaria epidemics in north-west Tanzania.
AB  - BACKGROUND: Malaria is a significant public health problem in Tanzania.
      Approximately 16 million malaria cases are reported every year and 100,000 to
      125,000 deaths occur. Although most of Tanzania is endemic to malaria, epidemics
      occur in the highlands, notably in Kagera, a region that was subject to
      widespread malaria epidemics in 1997 and 1998. This study examined the
      relationship between climate and malaria incidence in Kagera with the aim of
      determining whether seasonal forecasts may assist in predicting malaria
      epidemics. METHODS: A regression analysis was performed on retrospective malaria
      and climatic data during each of the two annual malaria seasons to determine the
      climatic factors influencing malaria incidence. The ability of the DEMETER
      seasonal forecasting system in predicting the climatic anomalies associated with
      malaria epidemics was then assessed for each malaria season. RESULTS: It was
      found that malaria incidence is positively correlated with rainfall during the
      first season (Oct-Mar) (R-squared = 0.73, p < 0.01). For the second season (Apr
      Sep), high malaria incidence was associated with increased rainfall, but also
      with high maximum temperature during the first rainy season (multiple R-squared =
      0.79, p < 0.01). The robustness of these statistical models was tested by
      excluding the two epidemic years from the regression analysis. DEMETER would have
      been unable to predict the heavy El Nino rains associated with the 1998 epidemic.
      Nevertheless, this epidemic could still have been predicted using the temperature
      forecasts alone. The 1997 epidemic could have been predicted from observed
      temperatures in the preceding season, but the consideration of the rainfall
      forecasts would have improved the temperature-only forecasts over the remaining
      years. CONCLUSION: These results demonstrate the potential of a seasonal
      forecasting system in the development of a malaria early warning system in Kagera
      region.

PMID- 18062818
TI  - N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes:
      correlation with glutamine synthase dysfunction.
AB  - BACKGROUND: HIV envelope gp 120 glycoprotein is released during active HIV
      infection of brain macrophages thereby generating inflammation and oxidative
      stress which contribute to the development of the AIDS-Dementia Complex (ADC).
      Gp120 has also been found capable to generate excitotoxic effect on brain tissue
      via enhancement of glutamatergic neurotransmission, leading to neuronal and
      astroglial damage, though the mechanism is still to be better understood. Here we
      investigated on the effect of N-acetylcysteine (NAC), on gp120-induced damage in
      human cultured astroglial cells and the possible contribution of gp120-related
      reacting oxygen species (ROS) in the imbalanced activity of glutamine synthase
      (GS), the enzyme that metabolizes glutamate into glutamine within astroglial
      cells playing a neuroprotective role in brain disorders. RESULTS: Incubation of
      Lipari human cultured astroglial cells with gp 120 (0.1-10 nM) produced a
      significant reduction of astroglial cell viability and apoptosis as evaluated by
      TUNEL reaction and flow cytometric analysis (FACS). This effect was accompanied
      by lipid peroxidation as detected by means of malondialdehyde assay (MDA). In
      addition, gp 120 reduced both glutamine concentration in astroglial cell
      supernatants and GS expression as detected by immunocytochemistry and western
      blotting analysis. Pre-treatment of cells with NAC (0.5-5 mM), dose-dependently
      antagonised astroglial apoptotic cell death induced by gp 120, an effect
      accompanied by significant attenuation of MDA accumulation. Furthermore, both
      effects were closely associated with a significant recovery of glutamine levels
      in cell supernatants and by GS expression, thus suggesting that overproduction of
      free radicals might contribute in gp 120-related dysfunction of GS in astroglial
      cells. CONCLUSION: In conclusion, the present experiments demonstrate that gp 120
      is toxic to astroglial cells, an effect accompanied by lipid peroxidation and by
      altered glutamine release. All the effects of gp120 on astroglial cells were
      counteracted by NAC thus suggesting a novel and potentially useful approach in
      the treatment of glutammatergic disorders found in HAD patients.

PMID- 18062819
TI  - The use and misuse of health research by parliamentary politicians during the
      development of a national smokefree law.
AB  - BACKGROUND: We investigated the ways in which research evidence about the health
      effects from secondhand smoke (SHS) and smokefree policies was publicly used or
      regarded by New Zealand parliamentary politicians, during efforts to strengthen a
      smokefree law (ie, from 1997 to 2005). METHODS: A documentary case study used
      published and unpublished material recording the use of research evidence by
      politicians. The material was collected for the period 1997-2005 from the
      parliamentary record, media and other databases. Additional searches were made to
      provide context for the politicians who used research. RESULTS: Major themes
      identified included: (a) the employment of local estimates of SHS mortality, (b)
      linking specific health effects (eg, cancer) to SHS exposure, (c) a focus on the
      use of research relevant to bar workers, and (d) the use of research to downgrade
      the health effects, and attacks on the credibility of research showing health
      effects from SHS. Almost half of the 21 Members of Parliament (MPs), who spoke in
      parliament about SHS research during 2000-2005, denied or were sceptical about
      SHS harm. At least five MPs used tobacco industry funded or disseminated versions
      of research. There was some indirect evidence that the degree of exposure to the
      health sector, or the tobacco industry and its allies, may have been factors in
      the use by MPs of the research. POLICY IMPLICATIONS: The willingness of some of
      this group of politicians to adopt tobacco industry arguments suggests possible
      options within health promotion. These include the better enforcement of consumer
      protection laws (preventing deceptive information by the tobacco industry and its
      allies), and the adoption of an increased focus on tobacco industry behaviour
      within tobacco control efforts. These moves may have beneficial effects for the
      use of research in public health policymaking. The strengthening by the health
      sector of its advocacy capacity and effectiveness may also be a crucial step in
      the better use of research by politicians in the policymaking process.

PMID- 18062821
TI  - Canada's implementation of the Paragraph 6 Decision: is it sustainable public
      policy?
AB  - BACKGROUND: Following the Implementation of Paragraph 6 of the Doha Declaration
      on TRIPS and Public Health, Canada was among the first countries globally to
      amend its patent law, which resulted in Canada's Access to Medicines Regime
      (CAMR). CAMR allows the production and export of generic drugs to developing
      countries without the requisite manufacturing capacity to undertake a domestic
      compulsory license. CAMR has been the subject of much criticism lodged at its
      inability to ensure fast access to urgent medicines for least developing and
      developing countries in need. Only recently did the Canadian government grant
      Apotex the compulsory licenses required under CAMR to produce and export
      antiretroviral therapy to Rwanda's population. METHODS: The objective of this
      research is to investigate whether the CAMR can feasibly achieve its humanitarian
      objectives given the political interests embedded in the crafting of the
      legislation. We used a political economy framework to analyze the effect of
      varied institutions, political processes, and economic interests on public policy
      outcomes. In-depth, semi-structured interviews were conducted with nineteen key
      stakeholders from government, civil society and industry. Qualitative data
      analysis was performed using open-coding for themes, analyzing by stakeholder
      group. RESULTS: CAMR is removed from the realities of developing countries and
      the pharmaceutical market. The legislation needs to include commercial incentives
      to galvanize the generic drug industry to make use of this legislation. CAMR
      assumes that developing country governments have the requisite knowledge and
      human resource capacity to make use of the regime, which is not the case. The
      legislation does not offer sufficient incentives for countries to turn to Canada
      when needed drugs may be procured cheaply from countries such as India. In the
      long term, developing and least developing countries seek sustainable solutions
      to meet the health needs of their population, including developing their own
      capacity and local industries. CONCLUSION: CAMR is symbolically meaningful but in
      practice, limited. The Rwanda case will be noteworthy in terms of the future of
      the legislation. To meet its intended international health objectives, this
      legislation needs to be better informed of developing country needs and global
      pharmaceutical market imperatives. Finally, we contend that serious public policy
      change cannot strike a balance between all vested interests. Above all, any
      feasible policy that aims to facilitate compulsory licensing must prioritize
      public health over trade or economic interests.

PMID- 18062820
TI  - Changes in sedation management in German intensive care units between 2002 and
      2006: a national follow-up survey.
AB  - BACKGROUND: The aim of this study, conducted in 2006, was to find out whether
      changes in sedation management in German intensive care units took place in
      comparison with our survey from 2002. METHODS: We conducted a follow-up survey
      with a descriptive and comparative cross-sectional multi-center design. A postal
      survey was sent between January and May 2006, up to four times, to the same 269
      hospitals that participated in our first survey in 2002. The same questionnaire
      as in 2002 was used with a few additional questions. RESULTS: Two hundred
      fourteen (82%) hospitals replied. Sixty-seven percent of the hospitals carried
      out changes in sedation management since the 2002 survey. Reasons for changes
      were published literature (46%), national guidelines (29%), and scientific
      lectures (32%). Sedation protocols (8% versus 52%) and a sedation scale (21%
      versus 46%) were used significantly more frequently. During sedation periods of
      up to 24 hours, significantly less midazolam was used (46% versus 35%). In
      comparison to 2002, sufentanil and epidural analgesia were used much more
      frequently in all phases of sedation, and fentanyl more rarely. For periods of
      greater than 72 hours, remifentanil was used more often. A daily sedation break
      was introduced by 34% of the hospitals, and a pain scale by 21%. CONCLUSION: The
      increased implementation of protocols and scoring systems for the measurement of
      sedation depth and analgesia, a daily sedation break, and the use of more short
      acting analgesics and sedatives account for more patient-oriented analgesia and
      sedation in 2006 compared with 2002.

PMID- 18062822
TI  - Functional improvement after total knee arthroplasty revision: new observations
      on the dimensional nature of outcome.
AB  - BACKGROUND: Despite the numerous outcomes measures described it remains unclear
      what aspects of patient outcome are important in determining actual improvement
      following total knee arthroplasty revisions (TKAR). We performed a prospective
      cohort study of TKAR to determine the components of clinical improvement and how
      they are related and best measured. METHODS: An improvement scale was devised
      utilizing data from 186 consecutive TKAR patients on SF-36 physical (PCS) and
      mental (MCS) components, Western Ontario and McMaster Universities Osteoarthritis
      (WOMAC) Index, Knee Society Score (KSS), a novel Activity Scale (AS) and a
      physician derived severity assessment scale performed both preoperatively and at
      6 month post-operative follow-up. The change in each of these scores was analyzed
      using factor analysis, deriving a composite improvement scale. RESULTS: All the
      instruments demonstrated statistically significantly better scores following TKAR
      (except the SF-36 MCS). Furthermore, all significant correlations between the
      scores were positive. Statistical factor analysis demonstrated that scores could
      be arranged into 4 related factor groupings with high internal consistency
      (Cronbach Alpha = 0.7). Factor 1 reflected patient perceived functional outcomes,
      Factor 2 activity levels, Factor 3 the MCS and Factor 4 the KSS. CONCLUSION: This
      study demonstrates that improvement following TKAR has a multidimensional
      structure. The improvement scales represent a more coordinated method of the
      previously fragmented analysis of TKAR outcomes. This will improve assessment of
      the actual effectiveness of TKAR for patients and what aspects of improvement are
      most critical.

PMID- 18062824
TI  - Databases as policy instruments. About extending networks as evidence-based
      policy.
AB  - BACKGROUND: This article seeks to identify the role of databases in health
      policy. Access to information and communication technologies has changed
      traditional relationships between the state and professionals, creating new
      systems of surveillance and control. As a result, databases may have a profound
      effect on controlling clinical practice. METHODS: We conducted three case studies
      to reconstruct the development and use of databases as policy instruments. Each
      database was intended to be employed to control the use of one particular
      pharmaceutical in the Netherlands (growth hormone, antiretroviral drugs for HIV
      and Taxol, respectively). We studied the archives of the Dutch Health Insurance
      Board, conducted in-depth interviews with key informants and organized two focus
      groups, all focused on the use of databases both in policy circles and in
      clinical practice. RESULTS: Our results demonstrate that policy makers hardly
      used the databases, neither for cost control nor for quality assurance. Further
      analysis revealed that these databases facilitated self-regulation and quality
      assurance by (national) bodies of professionals, resulting in restrictive
      prescription behavior amongst physicians. CONCLUSION: The databases fulfill
      control functions that were formerly located within the policy realm. The
      databases facilitate collaboration between policy makers and physicians, since
      they enable quality assurance by professionals. Delegating regulatory authority
      downwards into a network of physicians who control the use of pharmaceuticals
      seems to be a good alternative for centralized control on the basis of monitoring
      data.

PMID- 18062825
TI  - Influence of the transmission function on a simulated pathogen spread within a
      population.
AB  - The mathematical function for the horizontal transmission of a pathogen is a
      driving force of epidemiological models. This paper aims at studying the
      influence of different transmission functions on a simulated pathogen spread.
      These functions were chosen in the literature and their biological relevance is
      discussed. A theoretical SIR (Susceptible-Infectious-Recovered) model was used to
      study the effect of the function used on simulated results. With a constant total
      population size, different equilibrium values for the number of infectious (NI)
      were reached, depending on the transmission function used. With an increasing
      population size, the transmission functions could be assimilated to either
      density-dependent (DD), where an equilibrium was obtained, or frequency-dependent
      (FD), with an exponential increase in NI. An analytical study corroborated the
      simulated results. As a conclusion, the choice between the different transmission
      functions, particularly between DD and FD, must be carefully considered for a
      varying population size.

PMID- 18062823
TI  - Discordance between microvascular permeability and leukocyte dynamics in septic
      inducible nitric oxide synthase deficient mice.
AB  - INTRODUCTION: Microvascular dysfunction causing intravascular leakage of fluid
      and protein contributes to hypotension and shock in sepsis. We tested the
      hypothesis that abrogation of inducible nitric oxide synthase (iNOS) activation
      would decrease leukocyte rolling, leukocyte adhesion, and microvascular leakage
      in sepsis. We compared wild-type mice made septic by cecal ligation and puncture
      with mice deficient in iNOS. METHODS: Leukocyte dynamics and microvascular
      permeability were assessed simultaneously by fluorescence intravital microscopy
      in the cremaster muscle 15 to 20 hours after induction of sepsis by cecal
      ligation and puncture in C57Bl/6 mice. Rolling and adhesion of leukocytes labeled
      with rhodamine and leakage of fluorescein isothiocyanate-conjugated albumin was
      measured in single nonbranching venules (25 to 40 microm) and compared among
      septic wild-type, septic iNOS-deficient transgenic, and sham-operated control
      mice. RESULTS: Leukocyte rolling and adhesion were increased in septic animals
      (61.6 +/- 14.4 cells/minute and 4.1 +/- 0.6 cells/100 microm per minute,
      respectively) as compared with control animals (8.5 +/- 2.3 cells/minute and 1.1
      +/- 0.2 cells/100 microm per minute, respectively; P < 0.001 for both). Rolling
      increased in iNOS-deficient septic mice (to 105.5 +/- 30.0 cells/minute, P =
      0.048, versus wild-type septic); adhesion was unchanged (5.1 +/- 0.5 cells/100
      microm per minute, P = 0.30). Sepsis produced an increase in leakage ratio in
      wild-type septic mice compared with controls (0.36 +/- 0.05 versus 0.08 +/- 0.01,
      P < 0.001). Leakage was attenuated in iNOS-deficient septic mice (0.12 +/- 0.02,
      P < 0.001, versus wild-type septic mice). CONCLUSION: Leukocyte adhesion and
      vascular leakage were discordant in this setting. The finding that septic iNOS
      deficient mice exhibited less microvascular leakage than wild-type septic mice
      despite equivalent increases in leukocyte adhesion suggests an important role for
      nitric oxide in modulating vascular permeability during sepsis.

PMID- 18062826
TI  - Coffee consumption and mortality in a 14-year follow-up of an elderly northern
      Finnish population.
AB  - The present study assessed the relationship between coffee consumption and
      mortality in a home-dwelling elderly population. A population-based cohort of 817
      men and women born in 1920 or earlier and living in northern Finland provided
      complete data on daily coffee consumption and other variables at the baseline
      examination in 1991-1992. Deaths were monitored through to the end of 2005 by
      national death certificates, resulting in 6960 person-years of follow-up. Hazard
      rate ratios for mortality by daily coffee intake were estimated by Poisson
      regression models adjusted for some known predictors of mortality. During 14.5
      years of follow-up, 623 deaths occurred. The total mortality rate was inversely
      related to the number of cups (average volume, 125 ml) of coffee consumed daily.
      After adjustment for age, sub-period of follow-up, sex, marital status, basic
      educational level, previous occupational group, current smoking, BMI, history of
      myocardial infarction, self-rated health and presence of diabetes, cognitive
      impairment or physical disability, the estimated relative risk reduction of total
      mortality per an increment of one more cup of coffee per d reported at baseline
      was 4 (95% CI 0, 8) %. The observed associations between coffee consumption and
      mortality from CVD, cancer, and other or unknown causes, respectively, were
      qualitatively similar to that of total mortality but the estimates were less
      precise. The effect of coffee consumption at baseline appeared to attenuate after
      10 years since the start of follow-up. The present study provides evidence for
      daily (caffeine-containing) coffee intake being inversely associated with
      mortality in the elderly.

PMID- 18062827
TI  - Serum fatty acid composition and indices of stearoyl-CoA desaturase activity are
      associated with systemic inflammation: longitudinal analyses in middle-aged men.
AB  - Altered fatty acid (FA) composition is related to insulin resistance and CVD. One
      possible mediator may be inflammation, but longitudinal data relating FA
      composition to inflammation taking insulin resistance into account are limited.
      We investigated the long-term association between FA composition and C-reactive
      protein (CRP) concentrations in a large population-based cohort study in 767 men
      followed for 20 years. The association between FA composition in serum
      cholesteryl esters at age 50 and CRP concentrations at age 70 was investigated
      using linear regression. In addition, desaturase activities (stearoyl-CoA
      desaturase-1 (SCD-1), Delta5- and Delta6-desaturase) were estimated using FA
      product-to-precursor ratios. Insulin resistance was measured directly at follow
      up by euglycaemic clamp. After adjusting for confounders (smoking, physical
      activity, alcohol intake, obesity and erythrocyte sedimentation rate) CRP
      concentrations were inversely associated with the proportion of 18:2n-6 (P =
      0.002) and positively associated with 16:1n-7 (P = 0.008), 18:1n-9 (P = 0.0003),
      20:5n-3 (P = 0.04) and estimated SCD-1 (P = 0.005) and Delta6-desaturase (P =
      0.02) activities. After adding insulin resistance to the model, 18:1n-9, 18:2n-6
      and SCD-1 remained significant predictors of CRP. A FA composition indicating low
      intake of 18:2n-6, high intake of SFA and high SCD-1 activity is, in a Swedish
      population of middle-aged men, associated with CRP concentrations 20 years later,
      even independently of obesity and insulin resistance.

PMID- 18062828
TI  - Lipid peroxidative stress and antioxidant defence status during ontogeny of
      rainbow trout ( Oncorhynchus mykiss).
AB  - The objective of the present study was to characterise some important antioxidant
      enzymes and their relationships with retinoids and lipid peroxidation during
      rainbow trout (Oncorhynchus mykiss) early development. Eggs were incubated at 7
      degrees C until the swim-up stage whereupon fry were fed two semi-purified diets
      with 0% (CO) and 8% (OX) oxidised lipid respectively for 2 months at 17 degrees
      C. The activities and gene expression of superoxide dismutase (SOD), catalase
      (CAT) and glutathione peroxidase (GPX) were determined as well as the levels of
      retinoids, F2-isoprostanes and lipid-soluble fluorescent products (LSFP) at
      various developmental stages. Only SOD had a detectable activity in embryos which
      increased during development and was linked with an increase of mitochondrial
      (SOD2) and cytosolic (SOD1) gene expression. SOD1 and SOD2 mRNA were more
      abundant in fry fed OX than in fry fed CO. CAT activity and gene expression also
      increased during development and were higher in fry fed OX compared with fry fed
      CO. Activity of Se-dependent GPX (Se-GPX) increased during development. The gene
      expression of cytosolic Se-GPX (GPX1) increased from hatching to 2-month-fed fry.
      Both phospholipid-hydroperoxide GPX and GPX1 genes were more expressed in fry fed
      OX than in fry fed CO. Retinoids decreased during development and, by 2 months,
      were lowered in fry fed OX compared with those fed CO. The levels of LSFP were
      higher in fry fed OX compared with fry fed CO. The present study demonstrates
      that antioxidant defence systems are active all through the development of
      rainbow trout and modulated by feeding oxidised lipid.

PMID- 18062829
TI  - Effect of long-term selenium yeast intervention on activity and gene expression
      of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers
      from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) pilot
      study.
AB  - Numerous mechanisms have been proposed to explain the anti-carcinogenic effects
      of Se, among them altered carcinogen metabolism. We investigated the effect of Se
      supplementation on activities of glutathione peroxidase (GPX), glutathione
      reductase (GR) and glutathione S-transferase (GST) in different blood
      compartments, and expression of selected phase 1 and phase 2 genes in leucocytes
      (GPX1, gamma-glutamylcysteine ligase catalytic subunit (GCLC), AP-1 transcription
      factor Fos-related antigen 1 (Fra1), NAD(P)H:quinone oxidoreductase (NQO1), and
      aryl hydrocarbon receptor repressor (AhRR)). Healthy elderly Danes (n 105; age
      71.3 (SD 4.26) years; 36% reporting use of multivitamin/mineral supplements)
      participated and were supplemented daily for 5 years with placebo, 100 microg,
      200 microg or 300 microg Se as Se-enriched yeast (SelenoPrecise). Blood samples
      were collected after 5 years of intervention. When all four groups were compared
      we found no effect of Se supplementation on plasma GPX or GR, on erythrocyte GPX,
      GR or GST, or on thrombocyte GR or GST. We found increased thrombocyte GPX
      activity at the two highest dosage levels in women only, but not in men. No
      effects on GPX1, NQO1 or AhRR gene expression were found. When all Se
      supplemented groups were pooled we found significant down regulation of the
      expression of some phase 2 genes (GCLC, Fra1). A significant increase in AhRR
      gene expression with smoking was found but was independent of Se supplementation.
      Down regulation of phase 2 genes could increase the risk of cancer. However,
      further studies are needed to establish whether the observed effect in leucocytes
      reflects a similar expression pattern in target tissues.

PMID- 18062830
TI  - Association of folate intake with the occurrence of depressive episodes in middle
      aged French men and women.
AB  - A low folate intake or a low folate status have been found to be associated with
      a higher frequency of depression in populations, but the existence and the
      direction of a causal link between folate intake or status and depression is
      still uncertain. The aim of this study was to seek the relation between the
      habitual folate intake in middle-aged men and women and the occurrence of
      depressive episodes. In a subsample of 1864 subjects (809 men and 1055 women)
      from the French SU.VI.MAX cohort, dietary habits have been measured at the
      beginning of the follow-up (six 24 h records) and declarations of antidepressant
      prescription, taken as markers of depressive episodes, have been recorded during
      the 8-year follow-up. No significant association was observed between folate
      intake and the risk of any depressive episode or of a single depressive episode
      during the follow-up, in both men and women. In contrast, the risk of
      experiencing recurrent depressive episodes (two or more) during the follow-up was
      strongly reduced in men with high folate intake (OR 0.25 (95 % CI 0.06, 0.98) for
      the highest tertile v. the lowest, P for trend 0.046). This association was not
      observed in women. These results suggest that a low folate intake may increase
      the risk of recurrent depression in men.

PMID- 18062831
TI  - Diet restriction and ageing in the dog: major observations over two decades.
AB  - This report reviews decade two of the lifetime diet restriction study of the dog.
      Labrador retrievers (n 48) were paired at age 6 weeks by sex and weight within
      each of seven litters, and assigned randomly within the pair to control-feeding
      (CF) or 25 % diet restriction (DR). Feeding began at age 8 weeks. The same diet
      was fed to all dogs; only the quantity differed. Major lifetime observations
      included 1.8 years longer median lifespan among diet-restricted dogs, with
      delayed onset of late life diseases, especially osteoarthritis. Long-term DR did
      not negatively affect skeletal maturation, structure or metabolism. Among all
      dogs, high static fat mass and declining lean body mass predicted death, most
      strongly at 1 year prior. Fat mass above 25 % was associated with increasing
      insulin resistance, which independently predicted lifespan and chronic diseases.
      Metabolizable energy requirement/lean body mass most accurately explained energy
      metabolism due to diet restriction; diet-restricted dogs required 17 % less
      energy to maintain each lean kilogram. Metabonomics-based urine metabolite
      trajectories reflected DR-related differences, suggesting that signals from gut
      microbiota may be involved in the DR longevity and health responses. Independent
      of feeding group, increased hazard of earlier death was associated with lower
      lymphoproliferative responses to phytohaemagglutinin, concanavalin A, and
      pokeweed mitogen; lower total lymphocytes, T-cells, CD4 and CD8 cells; lower CD8
      percentages and higher B-cell percentages. When diet group was taken into
      account, PWM responses and cell counts and percentages remained predictive of
      earlier death.

PMID- 18062832
TI  - Whey protein isolate and glycomacropeptide decrease weight gain and alter body
      composition in male Wistar rats.
AB  - The effect of feed protein type on body composition and growth has been examined.
      Evidence exists that whey protein concentrate is effective at limiting body fat
      expansion. The presence of caseinomacropeptide, a mixture of glycosylated and non
      glycosylated carbohydrate residues, in particular glycomacropeptide (GMP) in whey
      protein concentrate may be important for this effect. The influence of whey
      protein isolate (WPI) and GMP on weight gain and body composition was examined by
      feeding Wistar rats ad libitum for 7 weeks with five semi-purified American
      Institute of Nutrition-based diets differing in protein type: (1) casein; (2)
      barbequed beef; (3) control WPI (no GMP); (4) WPI+GMP at 100 g/kg; (5) WPI+GMP at
      200 g/kg. Body composition was assessed, and plasma samples were assayed for TAG,
      insulin and glucose. Body-weight gain was lower (- 21 %) on the control WPI diet
      relative to casein, with a non-significant influence associated with GMP
      inclusion (- 30 %), the effect being equivalent at both levels of GMP addition.
      Renal and carcass fat mass were reduced in the highest GMP diet when compared
      with WPI (P < 0.05). Plasma insulin was lowered by GMP at the highest addition
      compared with WPI alone (- 53 %; P < 0.01). Plasma TAG in the WPI+GMP (200 g/kg)
      group were lower (- 27 %; P < 0.05) than the casein and beef groups. In
      conclusion, GMP appears to have a significant additional influence when combined
      with WPI on fat accumulation. WPI alone appears to have the predominant influence
      accounting for 70 % of the overall effect on body-weight gain. Mechanisms for
      this effect have not been identified but food intake was not responsible.

PMID- 18062833
TI  - Effect of selenium and Ascaridia galli infection on antioxidant biomarkers in
      broiler chickens: a mathematical model for parasite reduction and host growth.
AB  - The activity of selenium-dependent glutathione peroxidase (GPX), liver
      concentration of vitamin E, and plasma and liver selenium levels were used for
      estimation of the antioxidant status of broiler chickens infected with Ascaridia
      galli. These biomarkers were recorded in an experiment covering 70 days p.i. At
      the same time the establishment rate of A. galli in chicken intestines, gain in
      the host body weight and chicken survival were studied. Broiler chickens (Cobb
      hybrids) were infected with 1450 embryonated A. galli eggs and treated with Sel
      plex. A mathematical model was applied to determine the rate of nematode
      reduction and the relative rate of gain of host body weight, which are essential
      kinetic parameters of parasite-host interaction. The activity of GPX increased
      with both elevated selenium and reduced infection levels. The concentrations of
      selenium and vitamin E, and the GPX activity in the infected chickens
      demonstrated a similar pattern of change with time after day 30 p.i. The
      supplementation of the broilers with dietary selenium in the form of Sel-plex
      improved their antioxidant status. Increases by 29% in vitamin E concentration,
      15% in GPX activity, and 22% in liver selenium concentration, respectively, were
      recorded in the infected and treated, compared to infected and untreated
      broilers.

PMID- 18062834
TI  - Sexual dimorphism in campylobacteriosis.
AB  - Sexual dimorphism in infectious diseases whereby disease incidence is more
      prevalent in one gender has been reported repeatedly in the scientific
      literature. Both behavioural and physiological differences have been suggested as
      a cause of this gender bias but there is a paucity of data to support either of
      these viewpoints. Here it is hypothesized that for campylobacteriosis
      physiological factors play an important role in the higher incidence in males. We
      demonstrate in the human population (from several countries in three continents)
      that this bias exists in young children (<1 year) where behavioural differences
      between genders are likely to be minimal. Further we demonstrate this difference
      in an animal model where both infection rates and shedding rates of the organism
      are greater in male mice.

PMID- 18062835
TI  - Novel insight in the association between salmonellosis or campylobacteriosis and
      chronic illness, and the role of host genetics in susceptibility to these
      diseases.
AB  - We studied the role of host genetics in the susceptibility to severe Salmonella
      and Campylobacter infections and chronic sequelae of these infections.
      Participants of a previous case-control study were sent a buccal swab kit and a
      questionnaire about occurrence of chronic sequelae. Single nucleotide
      polymorphisms (SNPs) in the TLR4 (rs4986790), IFNG (rs2430561 and rs1861493),
      STAT1 (rs1914408), IL1B (rs16944), NRAMP (SLC11A1 rs2276631), JUN (rs11688) and
      VDR (rs10735810) genes were determined. In total, 687 controls, 457 Campylobacter
      cases and 193 Salmonella cases participated. None of the SNPs were associated
      with Campylobacter or Salmonella infections. None of the participants developed
      Guillain-Barre, Miller-Fisher or Reiter's syndrome. Reactive arthritis occurred
      in 5% and 2% of cases and controls, respectively. Campylobacter cases more
      frequently experienced gastroenteritis episodes than controls. Campylobacter or
      Salmonella infection in women, use of proton pump inhibitors and an SNP in the
      IFNG gene were independent risk factors for reactive arthritis. Another SNP in
      the IFNG gene and use of proton pump inhibitors were risk factors for recurrent
      episodes of gastroenteritis. In conclusion, reactive arthritis and recurrent
      gastroenteritis episodes are common after infection and host genetic factors play
      a role in susceptibility to these long-term health effects.

PMID- 18062836
TI  - Exploration of the acarine fauna on coconut palm in Brazil with emphasis on
      Aceria guerreronis (Acari: Eriophyidae) and its natural enemies.
AB  - Coconut is an important crop in tropical and subtropical regions. Among the mites
      that infest coconut palms, Aceria guerreronis Keifer is economically the most
      important. We conducted surveys throughout the coconut growing areas of Brazil.
      Samples were taken from attached coconuts, leaflets, fallen coconuts and
      inflorescences of coconut palms in 112 localities aiming to determine the
      occurrence and the distribution of phytophagous mites, particularly A.
      guerreronis, and associated natural enemies. Aceria guerreronis was the most
      abundant phytophagous mite followed by Steneotarsonemus concavuscutum Lofego &
      Gondim Jr. and Steneotarsonemus furcatus De Leon (Tarsonemidae). Infestation by
      A. guerreronis was recorded in 87% of the visited localities. About 81% of all
      predatory mites belonged to the family Phytoseiidae, mainly represented by
      Neoseiulus paspalivorus De Leon, Neoseiulus baraki Athias-Henriot and Amblyseius
      largoensis Muma; 12% were Ascidae, mainly Proctolaelaps bickleyi Bram,
      Proctolaelaps sp nov and Lasioseius subterraneus Chant. Neoseiulus paspalivorus
      and N. baraki were the most abundant predators on attached coconuts. Ascidae were
      predominant on fallen coconuts, while A. largoensis was predominant on leaflets;
      no mites were found on branches of inflorescences. Leaflets harboured higher mite
      diversity than the attached coconuts. Mite diversity was the highest in the state
      Para and on palms surrounded by seasonal forests and Amazonian rain-forests.
      Neoseiulus paspalivorus, N. baraki and P. bickleyi were identified as the most
      promising predators of A. guerreronis. Analyses of the influence of climatic
      factors revealed that dry ambient conditions favour the establishment of A.
      guerreronis. Neoseiulus paspalivorus and N. baraki have differing climatic
      requirements; the former being more abundant in warm and dry areas, the latter
      prevailing in moderately tempered and humid areas. We discuss the significance of
      our findings for natural and biological control of A. guerreronis.

PMID- 18062837
TI  - Interspecific competition between Diadegma semiclausum Hellen and Diadegma
      mollipla (Holmgren), parasitoids of the diamondback moth, Plutella xylostella
      (L), feeding on a new host plant.
AB  - Interspecific competition between an introduced parasitoid species aimed at
      controlling a herbivorous pest species and a native parasitoid parasitising the
      same host may influence the success of classical biological control programmes.
      In Kenya, interspecific competition between an introduced and a local parasitoid
      on two diamondback moth populations (DBM, Plutella xylostella) was investigated
      on two different host plants. We tested simultaneous and delayed competition of
      the local parasitoid Diadegma mollipla Holmgren and its exotic congenus D.
      semiclausum Hellen on a newly aquired DBM host plant (snowpea) in the laboratory.
      Under simultaneous competition, D. mollipla produced more progeny than D.
      semiclausum on snowpea. A head start of D. Mollipla, of four and eight hours
      before its congenus was introduced, resulted in a similar number of progeny of
      both species. In delayed competition (time intervals of 24 h, 48 h and 72 h),
      progeny production was similar for both parasitoids when the time interval was 24
      h, irrespective of which species parasitized first. More progeny was produced by
      the species which attacked first, when the time interval was greater than 24 h,
      although it was only significant at 72 h. Competitive abilites of both
      parasitoids on the new host plant differed largely between laboratory and semi
      field conditions. The influence of two host plants (snowpea and cabbage) on
      competition was studied in the greenhouse with different host and parasitoid
      densities. Parasitism levels of D. semiclausum were significantly higher than
      those of D. mollipla, regardless of host plant, host and parasitoid densities,
      but progeny production of D. mollipla on snowpea was still slightly higher than
      on cabbage. As compared to the confinement of parasitoids and larvae to small
      containers, D. mollipla parasitized very few larvae in the cages. Competitive
      ability of the two parasitoid species tested was influenced both by the density
      of the searching females and by parameters related to either the host plant
      and/or the herbivorous hosts.

PMID- 18062838
TI  - Patterns of acoustic variation in Cicada barbara Stal (Hemiptera, Cicadoidea)
      from the Iberian Peninsula and Morocco.
AB  - Field recordings of the calling song and of an amplitude modulated signal
      produced by males of Cicada barbara from North Africa and the Iberian Peninsula
      were analysed in order to assess the geographical acoustic variation and the
      potential usefulness of acoustic data in the discrimination of subspecies and
      populations. Sound recordings were digitized and the frequency and temporal
      properties of the calls of each cicada were analysed. In all regions studied,
      peak frequency, quartiles 25, 50 and 75% and syllable rate showed low
      coefficients of variation suggesting inherent static properties. All frequency
      variables were correlated with the latitude, decreasing from south to north. In
      addition, most acoustic variables of the calling song showed significant
      differences between regions, and PCA and DFA analyses supported a partitioning
      within this species between Iberian Peninsula+Ceuta and Morocco, corroborating
      mtDNA data on the same species. Therefore, the subspecific division of C. barbara
      into C. barbara barbara from Morocco and C. barbara lusitanica from Portugal,
      Spain and Ceuta finds support from the present acoustic analyses, a result which
      is also reinforced by molecular markers.

PMID- 18062839
TI  - Population structure of Cicada barbara Stal (Hemiptera, Cicadoidea) from the
      Iberian Peninsula and Morocco based on mitochondrial DNA analysis.
AB  - We assess the genetic history and population structure of Cicada barbara in
      Morocco and the Iberian Peninsula, based on analysis of the mitochondrial
      cytochrome b gene. The divergence between Morocco and the Iberian Peninsula
      populations was strongly corroborated by the molecular data, suggesting
      genetically isolated populations with a low level of gene flow. The Ceuta
      population from Spanish North Africa was more similar to the Iberian populations
      than the surrounding Moroccan populations, suggesting that the Strait of
      Gibraltar has not been acting as a strict barrier to dispersal while the Rif
      Mountains have. The Iberian Peninsula specimens showed a signature of demographic
      expansion before that which occurred in Morocco, but some of the assumptions
      related to the demographic parameters should be considered with caution due to
      the small genetic variation found. The high haplotype diversity found in Morocco
      implies higher demographic stability than in the Iberian Peninsula populations.
      These results do not, however, suggest a Moroccan origin for Iberian cicadas; but
      the most northwest region in Africa, such as Ceuta, might have acted as a
      southern refuge for Iberian cicadas during the most severe climatic conditions,
      from where they could expand north when climate improved. The separation of two
      subspecies within C. barbara (C. barbara lusitanica and C. barbara barbara) finds
      support with these results.

PMID- 18062840
TI  - Dietary intake and development of a quantitative food-frequency questionnaire for
      a lifestyle intervention to reduce the risk of chronic diseases in Canadian First
      Nations in north-western Ontario.
AB  - OBJECTIVES: To characterise the diet of First Nations in north-western Ontario,
      highlight foods for a lifestyle intervention and develop a quantitative food
      frequency questionnaire (QFFQ). DESIGN: Cross-sectional survey using single 24 h
      dietary recalls. SETTING: Eight remote and semi-remote First Nations reserves in
      north-western Ontario. SUBJECTS: 129 First Nations (Oji-Cree and Ojibway) men and
      women aged between 18 and 80 years. RESULTS: The greatest contributors to energy
      were breads, pasta dishes and chips (contributing over 20 % to total energy
      intake). 'Added fats' such as butter and margarine added to breads and vegetables
      made up the single largest source of total fat intake (8.4 %). The largest
      contributors to sugar were sugar itself, soda and other sweetened beverages
      (contributing over 45 % combined). The mean number of servings consumed of
      fruits, vegetables and dairy products were much lower than recommended. The mean
      daily meat intake was more than twice that recommended. A 119-item QFFQ was
      developed including seven bread items, five soups or stews, 24 meat- or fish
      based dishes, eight rice or pasta dishes, nine fruits and 14 vegetables.
      Frequency of consumption was assessed by eight categories ranging from 'Never or
      less than one time in one month' to 'two or more times a day'. CONCLUSION: We
      were able to highlight foods for intervention to improve dietary intake based on
      the major sources of energy, fat and sugar and the low consumption of fruit and
      vegetable items. The QFFQ is being used to evaluate a diet and lifestyle
      intervention in First Nations in north-western Ontario.

PMID- 18062841
TI  - Association of antioxidant vitamins and oxidative stress levels in pregnancy with
      infant growth during the first year of life.
AB  - OBJECTIVE: Whereas there are numerous reports in the literature relating the
      impact of maternal nutritional status on subsequent birth outcome, much less is
      known about the long-term impact on infant growth after birth. Therefore, we
      conducted a prospective cohort study to investigate the association of maternal
      micronutrient status (vitamins A, C and E, folate) and oxidative stress status in
      pregnancy with infant growth during the first year of life. DESIGN: Prospective
      cohort study. SETTING: Outpatient clinic of obstetrics, Ewha Womans University
      Hospital, Seoul, South Korea. SUBJECTS AND METHODS: Two groups were constructed
      for this study - the Ewha pregnancy cohort (n = 677) and the infant growth cohort
      comprising follow-up live newborns of all the recruited pregnant women (n = 317).
      Maternal serum vitamin and urinary oxidative stress levels were collected and
      infant weights and heights were measured at birth and at 6 and 12 months after
      birth. RESULTS: Division of the subjects into folate-deficient and normal groups
      revealed that infant weight and height at 0, 6 and 12 months were adversely
      affected by folate deficiency. High maternal vitamin C was associated with
      increased infant weight and height at birth and after birth. CONCLUSION: Our
      findings indicate the importance of preventing folate deficiency and
      supplementing vitamin C during pregnancy.

PMID- 18062842
TI  - Healthy whole-grain choices for children and parents: a multi-component school
      based pilot intervention.
AB  - OBJECTIVE: The aim of the present study was to pilot-test a school-based
      intervention designed to increase consumption of whole grains by 4th and 5th
      grade children. DESIGN: This multi-component school-based pilot intervention
      utilised a quasi-experimental study design (intervention and comparison schools)
      that consisted of a five-lesson classroom curriculum based on Social Cognitive
      Theory, school cafeteria menu modifications to increase the availability of whole
      grain foods and family-oriented activities. Meal observations of children
      estimated intake of whole grains at lunch. Children and parents completed
      questionnaires to assess changes in knowledge, availability, self-efficacy, usual
      food choice and role modelling. SETTING/SAMPLE: Parent/child pairs from two
      schools in the Minneapolis metropolitan area; 67 in the intervention and 83 in
      the comparison school. RESULTS: Whole-grain consumption at the lunch meal
      increased by 1 serving (P < 0.0001) and refined-grain consumption decreased by 1
      serving for children in the intervention school compared with the comparison
      school post-intervention (P < 0.001). Whole-grain foods were more available in
      the lunches served to children in the intervention school compared with the
      comparison school post-intervention (P < 0.0001). The ability to identify whole
      grain foods by children in both schools increased, with a trend towards a greater
      increase in the intervention school (P = 0.06). Parenting scores for scales for
      role modelling (P < 0.001) and enabling behaviours (P < 0.05) were significantly
      greater for parents in the intervention school compared with the comparison
      school post-intervention. CONCLUSIONS: The multi-component school-based programme
      implemented in the current study successfully increased the intake of whole-grain
      foods by children.

PMID- 18062843
TI  - Dietary lipoic acid-dependent changes in the activity and mRNA levels of hepatic
      lipogenic enzymes in rats.
AB  - Effects of dietary alpha-lipoic acid on hepatic and serum lipid concentrations
      and the activity and mRNA levels of lipogenic enzymes were examined in rats. Rats
      were fed experimental diets containing varying amounts of lipoic acid (0, 1, 2.5,
      5 g/kg) for 21 d. Lipoic acid profoundly decreased serum and liver concentrations
      of TAG, and also lowered serum concentrations of phospholipid and NEFA, and the
      concentration of cholesterol in the liver. A hypoglycaemic effect of this
      compound was also observed. Lipoic acid dose-dependently decreased the activity
      and mRNA levels of fatty acid synthase, ATP-citrate lyase, glucose 6-phosphate
      dehydrogenase, malic enzyme and pyruvate kinase in the liver despite that
      reductions were considerably attenuated in the NADPH-producing enzymes. This
      compound also dose-dependently lowered the mRNA levels of spot 14, adiponutrin,
      stearoyl-CoA desaturase 1, and Delta5- and Delta6-desaturases. In addition,
      lipoic acid dose-dependently lowered serum concentrations of insulin and leptin,
      but increased those of adiponectin. Lipoic acid appeared to reduce hepatic
      lipogenesis and hence decreases serum and liver lipid levels. Alterations in
      serum concentrations of insulin and (or) adiponectin may trigger this
      consequence.

PMID- 18062844
TI  - Epistemological beliefs in child care: implications for vocational education.
AB  - BACKGROUND: The quality of child care is of social and economic significance
      worldwide. The beliefs that child care workers hold about knowing and knowledge
      (epistemological beliefs) influence the quality of their professional work.
      However, attention to epistemological beliefs is rarely a focus in vocational
      education programmes. AIM: The aim of this study was to investigate the nature of
      child care students' epistemological beliefs. SAMPLE(S): All first- and second
      year students completing a Diploma of Children's Services at three separate
      training institutes in a large metropolitan area in Australia were invited to
      participate in the study. There were 46 first- and 31 second-year students (77 in
      total, 71 females). METHOD: This study used semi-structured interviews based on a
      child care scenario to enable students to articulate their epistemological
      beliefs. A descriptive-interpretative approach in which interviews were analysed
      for patterns of meaning was used in the content analysis. The categories, based
      on the work of Kuhn and Weinstock (2002), included objectivism, subjectivism, and
      evaluativism. While this proved to be a useful framework, the authors remained
      open to new categories emerging. This constituted the interpretive component of
      the analysis. Therefore, the data were analysed using both data-driven and theory
      led approaches to analysis, which still made it possible to take account of many
      viewpoints before arriving at the categories of beliefs. The categories were
      audited by a second researcher to establish trustworthiness and credibility.
      RESULTS: The findings of this study revealed a range of epistemological beliefs;
      however, a new way of thinking about evaluativistic beliefs called 'basic
      evaluativism' emerged. This view of knowledge relates to the construction of
      evidence-based practice rather than knowledge as is typically the case in
      evaluativistic beliefs. CONCLUSIONS: Implications for the need to address
      epistemological beliefs in vocational education programmes for child care workers
      are discussed.

PMID- 18062845
TI  - Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of
      hydromorphone in the presence of alcohol.
AB  - OBJECTIVE: The purpose of this study was to investigate the pharmacokinetic
      properties of a novel, once-daily, controlled-release formulation of
      hydromorphone (OROS hydromorphone) in the presence of alcohol. RESEARCH DESIGN
      AND METHODS: In a single-centre, open-label, four-treatment, four-period, four
      sequence, crossover study, two groups of 24 healthy subjects (fasted or fed) were
      randomised to receive four single doses of OROS hydromorphone 16 mg with
      solutions of either 0%, 4%, 20% or 40% alcohol, and with a naltrexone block. MAIN
      OUTCOME MEASURES: Plasma samples taken predose and at regular intervals up to 48
      h after dosing were assayed for hydromorphone concentrations; a mixed-effect
      analysis of variance was done on log-transformed data. Bioequivalence was
      concluded if 90% confidence intervals of treatment mean ratios were between 80%
      and 125%. RESULTS: Plasma hydromorphone concentrations were slightly higher after
      dosing with all alcohol treatments in both the fasted and fed subject groups.
      Median T(max) values were between 12 and 16 h and ranges were similar for all
      treatments. C(max) values increased after alcohol compared with no alcohol, with
      the increase slightly lower in the fed state. The greatest mean increase in
      C(max) observed was 1.3-fold in the fasted state and 1.1-fold in the fed state.
      Confidence intervals were within 80-125% for AUC but were slightly higher for
      C(max). CONCLUSIONS: The pharmacokinetics of once-daily OROS hydromorphone were
      only minimally affected by alcohol, with no dose dumping of hydromorphone. The
      results indicate that the controlled-release properties of this formulation are
      maintained in the presence of alcohol.

PMID- 18062846
TI  - Comparison of the safety and efficacy of loteprednol 0.5%/tobramycin 0.3% with
      dexamethasone 0.1%/tobramycin 0.3% in the treatment of
      blepharokeratoconjunctivitis.
AB  - OBJECTIVE: This study compared the safety and efficacy of loteprednol etabonate
      0.5%/tobramycin 0.3% (LE/T; Zylet) with dexamethasone 0.1%/tobramycin 0.3% (DM/T;
      Tobradex) in the treatment of ocular inflammation associated with
      blepharokeratoconjunctivitis. RESEARCH DESIGN AND METHODS: This was a
      multicenter, randomized, investigator-masked, parallel-group study. Subjects with
      clinically diagnosed blepharokeratocon-junctivitis in at least one eye were
      randomized to LE/T (n = 138) or DM/T (n = 138) administered four times per day,
      for 14 days. The primary efficacy endpoint was the change from baseline to Day 15
      (+/- 1 day) in the signs and symptoms composite score using a non-inferiority
      metric to compare LE/T to DM/T. Safety endpoints included visual acuity (VA),
      biomicroscopy, intraocular pressure (IOP) assessments, and adverse events.
      RESULTS: At Day 15, the mean (SD) change from baseline in the signs and symptoms
      composite score was -15.2 (7.3) for LE/T-treated subjects and -15.6 (7.7) for
      DM/T-treated subjects. The upper bound of the 90% confidence interval for the
      difference in change from baseline was less than the non-inferiority margin not
      only at Day 15 but also at Day 7 and Day 3 for both the intent-to-treat and per
      protocol populations. Subjects treated with DM/T experienced a significant
      increase in IOP versus those treated with LE/T at Day 7, Day 15, and overall
      (mean [SD] of 0.6 [2.3] vs, -0.1 [2.2], p = 0.03, 1.0 [3.0] vs. -0.1 [2.4], p =
      0.01, and 2.3 [2.3] vs. 1.6 [1.7], p = 0.02, respectively). CONCLUSIONS: LE/T
      satisfied the condition of non-inferiority to DM/T in decreasing the signs and
      symptoms of ocular inflammation associated with blepharokeratoconjunctivitis.
      Subjects treated with DM/T experienced more of an increase in IOP. LIMITATION:
      Although the single-masked design of this study could be considered a limitation,
      care was taken to ensure that the investigator was masked.

PMID- 18062847
TI  - Strategic defensiveness: public and private responses to group criticism.
AB  - This paper explores the strategic processes associated with responding to group
      criticism. In Experiment 1, Australians received criticism of their country from
      either an in-group or an out-group member. When participants believed their
      evaluations of the criticisms were private, they reported being more defensive
      when criticized by an out-group relative to an in-group member. However, this
      intergroup sensitivity effect disappeared on some measures when participants were
      led to believe their evaluations of the criticisms could be seen by an in-group
      audience. In Experiment 2, which focused on participants' identity as social
      science students, the attenuation of the intergroup sensitivity effect emerged
      only when the in-group audience was relatively high-status. Furthermore, in both
      experiments, increased reports of defensiveness in public only occurred in
      response to an in-group critic and not to an out-group critic. Theoretical and
      practical implications for intergroup and intragroup communication are discussed.

PMID- 18062848
TI  - Uncertainty and the influence of group norms in the attitude-behaviour
      relationship.
AB  - Two studies were conducted to examine the impact of subjective uncertainty on
      conformity to group norms in the attitude-behaviour context. In both studies,
      subjective uncertainty was manipulated using a deliberative mindset manipulation
      (McGregor, Zanna, Holmes, & Spencer, 2001). In Study 1 (N=106), participants were
      exposed to either an attitude-congruent or an attitude-incongruent in-group norm.
      In Study 2 (N=83), participants were exposed to either a congruent, incongruent,
      or an ambiguous in-group norm. Ranges of attitude-behaviour outcomes, including
      attitude-intention consistency and change in attitude-certainty, were assessed.
      In both studies, levels of group-normative behaviour varied as a function of
      uncertainty condition. In Study 1, conformity to group norms, as evidenced by
      variations in the level of attitude-intention consistency, was observed only in
      the high uncertainty condition. In Study 2, exposure to an ambiguous norm had
      different effects for those in the low and the high uncertainty conditions. In
      the low uncertainty condition, greatest conformity was observed in the attitude
      congruent norm condition compared with an attitude-congruent or ambiguous norm.
      In contrast, individuals in the high uncertainty condition displayed greatest
      conformity when exposed to either an attitude-congruent or an ambiguous in-group
      norm. The implications of these results for the role of subjective uncertainty in
      social influence processes are discussed.

PMID- 18062849
TI  - [Work features of the psychologist in the primary health care centers of the
      public health care system in Chile].
AB  - OBJECTIVES: To define work characteristics of psychologists in public primary
      health care centers in Chile and the degree to which their functions conform to
      the standards set by the National Plan on Mental Health and Psychiatry (NPMHP).
      METHODS: From December 2003 to November 2004, a cross-sectional, descriptive
      study was conducted employing a questionnaire sent to a nonrandom sample of 486
      professionals working in public primary care centers of Chile's 29 health
      districts. The total response rate was 34.4% (167 completed questionnaires). The
      questionnaire gathered general information and demographics; frequency,
      distribution, and type of activities performed; the mental health issues treated;
      personal perspectives on the efficiency of care, factors affecting interventions,
      and the quality of work conditions; and competence level regarding diagnosis and
      treatment strategies, as well as the educational background needed to fulfill the
      role of psychologist at the primary health care centers. Descriptive statistics
      with 95% confidence intervals were calculated for the quantitative data. Content
      analysis techniques were applied to the responses to open-ended questions.
      RESULTS: Considerably more time is being devoted to individual consultations and
      interventions than to group and community promotion and prevention activities.
      Over 93% of the survey participants were satisfied with their work and valued
      their peers; however, more than half gave a negative rating to their work
      conditions and job security. The majority indicated that preparation for the role
      must include coursework on the health system, specifically the primary health
      care setting, and topics such as clinical and group psychology, public health
      policy, and primary health care management and specifics. Most critical to the
      work were a knowledge of diagnostic tools and classification systems, i.e., the
      International Classification of Diseases and the Diagnostic and Statistical
      Manual of Mental Disorders. CONCLUSIONS: Contrary to NPMHP recommendations, the
      primary health care psychologists in Chile's public health care system are
      dedicating most of their time to individual counseling and therapy, rather than
      community activities designed to strengthen and promote mental health. In
      addition, a funding plan that supports NPMHP priorities is needed.

PMID- 18062850
TI  - Teens in trouble: cigarette use and risky behaviors among private, high school
      students in La Paz, Bolivia.
AB  - OBJECTIVE: To describe the prevalence of cigarette smoking and to identify risky
      behaviors associated with smoking among adolescents attending high schools in a
      district of La Paz, Bolivia. METHODS: The Youth Risk Behavior Survey was
      administered to a sample of 394 males and 182 females, from 13-18 years of age,
      at six, randomly-selected schools in District II of La Paz. Frequencies, chi
      square tests, and logistic regression were employed to identify factors
      associated with cigarette use during the 30 days prior to the survey. RESULTS:
      Approximately 40% of the sample (39.4% of males and 33.7% of females) had smoked
      cigarettes in the 30 days prior to interview. For both males and females,
      consumption of alcohol was the single greatest risk factor associated with
      cigarette use. The males and females who reported consuming at least one
      alcoholic beverage on three or more occasions in the previous 30 days were 22.3
      and 58.5 times (95% CIs: 6.7, 74.1 and 6.8, 502.6, respectively) more likely to
      smoke tobacco than those who reported no alcohol consumption. Additional risk
      factors included having participated in a physical fight, having carried a
      weapon, having had sexual intercourse, and having used illicit drugs during the
      previous 30 days. CONCLUSIONS: Because teenagers who smoke are also likely to
      engage in a variety of other risky behaviors, parents, school administrators, and
      health educators may wish to use smoking to identify at-risk individuals. Among
      Bolivian teenagers, interventions should focus on preventing cigarette use and
      associated risk behaviors.

PMID- 18062851
TI  - Nutritional status of urban schoolchildren of high and low socioeconomic status
      in Quetzaltenango, Guatemala.
AB  - OBJECTIVE: The prevalence of overweight and obesity is growing in children in
      many developing countries, increasing chronic disease risk. Our objective was to
      assess the prevalence of stunting, underweight, overweight, and obesity in
      schoolchildren 8 to 10 years old who were of high or low socioeconomic status
      (SES) in Quetzaltenango, which is the second largest city in Guatemala. METHODS:
      Between April and June 2005 we conducted a cross-sectional survey among 583
      children in private and public elementary schools, in which we measured height
      and weight. The Centers for Disease Control and Prevention (CDC) 2000 height-for
      age z-scores, weight-for-age z-scores, and body mass index-for-age centiles were
      used to define stunting, underweight, overweight, and obesity. RESULTS: Mean
      height, weight, and body mass index were significantly higher in the 327 children
      of high SES than in the 256 children of low SES, across sexes and age groups. The
      prevalence of stunting was significantly higher in low-SES children than in high
      SES ones (27.0% vs. 7.3%, P < 0.01) , and this was also true for underweight
      (14.1% versus 4.6%, P < 0.01). In contrast, the prevalence of overweight (17.7%
      versus 10.5%, P < 0.01) was higher in high-SES children than in low-SES ones; the
      same was true for obesity (14.4% versus 2.3%, P < 0.01). The prevalence of
      stunting among children of low SES, and the prevalence of overweight and obesity
      among children of high SES far exceeded the CDC 2000 reference ranges.
      CONCLUSIONS: A high prevalence of both stunting and excess body weight was found
      in this urban Guatemalan population, with notable contrasts between social
      classes. The obesity among high-income children indicates that the city is
      undergoing the nutrition transition, with further implications for future risks
      related to chronic disease. Nutrition and health interventions are needed to
      reduce these risks.

PMID- 18062852
TI  - [Epidemiological potential of multiple-cause-of-death data listed on death
      certificates, Brazil, 2003].
AB  - OBJECTIVE: To evaluate the automated processing and the epidemiological potential
      of multiple-cause-of-death data listed on death certificates in Brazil in 2003.
      METHODS: Data were obtained from the Brazilian Mortality Information System. The
      distribution of the number of causes per death certificate was processed using
      the Multiple Cause of Death Tabulator software and expressed as a percentage of
      the total deaths in federation units, regions, and in the country as a whole. For
      the main causes of death identified in Brazil in 2003, we calculated the rate at
      which each cause was listed as the "underlying cause of death" in relation to the
      total times the cause was mentioned. RESULTS: The mean number of causes of death
      per certificate ranged from 2.07 in the state of Maranhao to 3.15 in the state of
      Sao Paulo, and from 2.45 in the Northeast to 2.99 in the Mid-West. For the entire
      country, the mean number of causes of death per certificate was 2.81. External
      causes and neoplasms, unattended deaths, human immunodeficiency virus, and
      alcoholic liver disease were listed as the underlying cause more than 90% of the
      times they were mentioned; neoplasms, Chagas' disease, congenital malformations,
      ischemic heart diseases, and cerebrovascular diseases, between 70% to less than
      90% of the times they were mentioned; and pneumonias, heart failure, alcohol
      dependence, malnutrition, hypertensive diseases, anemias, ill-defined causes,
      prematurity, septicemias, and respiratory failure, less than 40% of the times
      they were mentioned. CONCLUSIONS: Although underlying causes of death are still
      essential to analyze historical trends, compare countries, and to guide the
      prevention of death, multiple-cause-of-death-data offer a new insight into the
      study of mortality. The combination of the two methodologies is more useful than
      the isolated use of either approach.

PMID- 18062853
TI  - A community-based education program about cervical cancer improves knowledge and
      screening behavior in Honduran women.
AB  - OBJECTIVES: This study examined changes in knowledge and behavior after a
      community-based cervical cancer education program in Honduras. METHODS: The
      program consisted of radio broadcasts targeting rural women and presentations to
      community nurses. The effectiveness of the radio broadcasts was assessed using a
      cross-sectional design (control groups n = 124, n = 243; intervention group n =
      233). A pre-/post-test design was used to evaluate the nurses' training program
      (n = 32). A subset of nurses (n = 16) was retested two years later. Evaluation
      included t tests, chi-square and Fisher exact analyses. RESULTS: The radio
      broadcast increased the proportion of women who were familiar with the term
      "cervical cancer," who could identify means of preventing cervical cancer, and
      who understood the purpose of the Pap smear. In addition, older and under
      screened women were successfully recruited for screening via radio. The nurses'
      program improved understanding of the correct use of the Pap smear, the age
      related risk of dysplasia, and the proper triage of abnormal results. The nurses
      retained a significant amount of knowledge two years after this training.
      CONCLUSIONS: In developing countries, inexpensive, community-based educational
      programs using radio broadcasts and lecture presentations can increase cervical
      cancer knowledge and improve screening behavior.

PMID- 18062854
TI  - [Nutritional status and body composition of poor children in the outlying
      neighborhoods of La Plata, Argentina].
AB  - OBJECTIVES: To evaluate nutritional status and body composition as indicators of
      quality of life among poor children served by neighborhood soup kitchens in La
      Plata, Argentina. METHODS: From April to November 2004, we conducted a cross
      sectional study of 608 healthy children from 1-11 years of age who were being
      served by two neighborhood soup kitchens in the outlying areas of the city of La
      Plata. The sample was stratified by age and sex. Height-for-age, weight-for age,
      and weight-for-height, were measured, as well as BMI, muscle mass and adipose
      tissue. Z-scores were computed for the data. Odds ratios and the respective 95%
      confidence intervals were calculated. RESULTS: Prevalence of low weight-for-age
      was 9%; low weight-for-height, 3%; and low height-for-age, 15%. The prevalence of
      overweight and obesity were 12.5% and 7.1%, respectively. Among the study sample,
      47.2% had low muscle mass and 20.4% had low adipose tissue. Among overweight and
      obese children, adipose tissue was 34.3% higher than that of the reference
      population, while muscle mass was 12.5% lower. CONCLUSIONS: Undernutrition and
      obesity are both found among the community of children studied. The high
      prevalence of delayed growth (i.e., low height-for-age), undernutrition (i.e.,
      low weight-for-age), and the acute lack of muscle mass even among overweight and
      obese children, seem to be part of the consequences of an inevitable process that
      unfolds in the face of adverse living conditions.

PMID- 18062855
TI  - Community-directed risk assessment of mercury exposure from gold mining in
      Suriname.
AB  - OBJECTIVES: The overarching objective of this project was to support the
      indigenous people in Kwakoegron, Suriname, in self-diagnosis of public and
      environmental health problems. The specific objectives, defined by the people of
      Kwakoegron were: (1) to determine for themselves if they are at risk of exposure
      to mercury (Hg) contamination, (2) to measure the extent of the Hg contamination
      problem, and (3) to initiate an intervention plan. METHODS: Field work was
      conducted from June 2005 to April 2006. Community members were trained to collect
      hair samples for analysis using methods designed to maximize sample quality and
      consistency and minimize cross-contamination. Each hair sample, of approximately
      20 mg, was weighed, added to the sample boat, and analyzed immediately without
      preservation or storage. Technicians educated in analytical chemistry and trained
      in the operation of the portable Lumex Zeeman Hg analyzer measured the total Hg
      (THg) for each hair sample. Confidential meetings were held with each person
      sampled and any questions were answered. Afterwards, a community meeting was held
      to reflect on the process, outcome, and future needs. RESULTS: Hair samples from
      16 of the 22 participants had Hg levels of 2.2-20.2 microg/g THg, exceeding
      normal THg levels for hair (2 microg/g THg). During the confidential, individual
      meetings and the followup community meeting, information was shared regarding the
      Hg levels found, what the numbers meant scientifically, what the potential health
      effects could be, and how exposure levels might be brought down. At the
      conclusion of the followup meeting, the Kwakoegron community proposed an
      intervention plan that had three principle parts: (1) routine analysis of Hg
      exposure to monitor trends and track the effects of exposure-reduction efforts;
      (2) routine health assessments to determine the effects of Hg exposure,
      particularly in children less than 5 years of age; and (3) fish advisories based
      on fish biology and trophic level or on the specific measurement of Hg levels in
      various fish species from various locations and different times throughout the
      year. CONCLUSIONS: This project showed that a democratic approach to science does
      not automatically compromise the orderly search for answers. Specifically, our
      experience in Kwakoegron suggests that the collaborative relationship that
      emerges by empowering an indigenous community to initiate its own research
      projects, and address the needs it identifies, can contribute positively to the
      risk assessment process. This project showed that when Kwakoegron was
      acknowledged as an equal partner, the risk assessment process led to an open
      exchange of information and an intervention plan that was both pragmatic and
      acceptable in the context of the community's unique social and cultural needs.

PMID- 18062856
TI  - [Old indicators for new problems: the relationship between sanitation and
      health].
AB  - OBJECTIVE: To review the literature published from 1995-2004 on the relationship
      between sanitation and health and to identify the main variables analyzed and the
      diseases or injuries used as markers of effect or environmental health. METHOD: A
      search of Medline, SciELO, and LILACS on "sanitation" and "health" and
      "indicator" and "water" produced 103 articles, 17 of which were considered
      relevant for the analysis. We identified the study design and the sanitation and
      health variables analyzed in each of the 17 studies. RESULTS: The most common
      study design was ecological and was employed in seven of the 17 studies. In most
      (10 studies), the health variable was diarrhea and sanitation variable was water
      quality. Fifteen studies reported a positive association between the health and
      sanitation variables. CONCLUSIONS: There are still many gaps in our understanding
      of sanitation and its role, especially in large urban centers that are dependent
      on water and sewerage systems and often lack alternative water sources.
      Ecological studies based on secondary data and specific surveys have been shown
      to be a good option for analyses correlating sanitation and health.

PMID- 18062859
TI  - Mutations along the hypothalamic-pituitary-gonadal axis affecting male
      reproduction.
AB  - Disorders in male reproductive function are caused by mutations of key genes at
      all levels of the hypothalamic-pituitary- testicular axis. They may affect the
      ontogeny and function of the hypothalamic centres governing gonadotrophin
      synthesis and secretion, the development of the anterior pituitary gland, the
      production of gonadotrophins and the function of their receptor genes, and
      finally the genes responsible for testicular hormone production and
      gametogenesis. This review focuses on mutations that affect the synthesis and
      secretion of hypothalamic gonadotrophin-releasing hormone, pituitary follicle
      stimulating hormone and luteinising hormone, as well as their testicular
      receptors, thus covering a selected group of genetic causes of hypo- and
      hypergonadotrophic male hypogonadism.

PMID- 18062860
TI  - Influence of endocrine disruptors on human male fertility.
AB  - It has been suggested that during the past five decades human sperm counts have
      declined and the incidence of testicular cancer, hypospadias and cryptorchidism
      has increased. Furthermore, geographical differences, with respect to these
      markers of male reproductive function, have been reported. According to a recent
      hypothesis, all these abnormalities of the male genital system do have a common
      cause, namely exposure to endocrine disruptors affecting the male in early fetal
      life. Reduced sperm production as well as congenital abnormalities of male
      genitalia can be evoked in laboratory animals by exposing them to chemicals with
      endocrine-disrupting effect, and in humans similar effects have been seen
      following accidental exposures to very high concentrations of these environmental
      toxicants. However, the evidence for association between levels of exposure found
      in the general population and serious adverse effects on male reproduction,
      including fertility, is still lacking. A recent European Union-supported study,
      on the effect of persistent organohalogen pollutants on human reproduction,
      failed to show any correlation between post-natal exposure levels and fertility.
      Future studies will reveal whether prenatal exposure does more strongly affect
      male fertility and whether genetic predisposition regulates the susceptibility of
      an individual to the adverse effects of endocrine disruptors.

PMID- 18062861
TI  - Gene polymorphisms and male infertility--a meta-analysis and literature review.
AB  - Many genetic polymorphisms have been studied extensively to elucidate their role
      in the pathophysiology of male infertility. This article presents a review of the
      literature following a thorough search of PubMed, a compilation of meta-analyses
      of studies reporting an association with male fertility where the population(s)
      could be clearly identified as fertile and/or infertile, and a summary of all
      polymorphisms that have been investigated in single case-control studies to date.
      The meta-analyses revealed significant associations between polymorphism and male
      fertility only for AZF gr/gr deletions (OR 1.81, 1.46-2.24 CI, P<0.00001) and
      MTHFR 677C-->T (OR 1.39, 1.15-2.69 95% CI, P=0.0006) but not for POLG, DAZL,
      USP26 or FSHR. The influence of CAG repeat length in AR remains open and debated.
      Genes encoding nuclear proteins (PRM1/2, TNP1/2) and ER1 are possible candidates
      for further examination, while the role of TAF7L remains unclear. Polymorphisms
      in 16 other genes have been investigated in single studies, but the results
      remain doubtful due to often small and heterogeneous cohorts and in the absence
      of independent replications. The genetic studies performed so far emphasize the
      complexity of male infertility as a presumably polygenetic trait amended by
      environmental, lifestyle or occupational factors.

PMID- 18062862
TI  - Hormonal and genetic control of testicular descent.
AB  - Cryptorchidism has the potential to affect the health of the human male. Although
      it is often considered a mild malformation, it represents the best-characterized
      risk factor for reduced fertility and testicular cancer. The aetiology of
      cryptorchidism remains, for the most part, unknown and cryptorchidism itself
      might be considered a complex disease. This reflects the intricate mechanisms
      regulating testicular development and descent from intra-abdominal location into
      the bottom of the scrotum, involving different anatomical and hormonal factors.
      Major actors of testicular descent are the Leydig cell-derived hormones
      testosterone and insulin-like factor 3, even if other factors may play a role.
      Although considerable evidence exists in animals to support a genetic cause, the
      genetic contribution to human cryptorchidism is only recently being elucidated.
      Environmental factors might also contribute to the aetiology of cryptorchidism
      and its increased incidence in recent years. Mutations in the gene for insulin
      like factor 3 and its receptor and in the androgen receptor gene explain a
      minority of cases of cryptorchidism, but research on genetic polymorphisms that
      may also influence susceptibility to endocrine disruptors is shedding light on
      this field.

PMID- 18062863
TI  - Hormonal treatment of male infertility: FSH.
AB  - FSH plays a crucial role in spermatogenesis. In the fetal and neonatal
      development stages, FSH activates the proliferation of the Sertoli cells and
      successively, during the pubertal phase, it influences the mitotic activity of
      the spermatogonia and encourages cellular differentiation, until arrival at the
      round spermatid stage. Because of its physiological role in spermatogenesis,
      various attempts have been made to treat idiopathic oligozoospermic men with FSH.
      However, the results obtained so far are still controversial. In this research,
      attention was focused on the possible criteria able to predict a seminal response
      to this specific hormonal treatment. Furthermore, the effectiveness of FSH
      therapy was evaluated in terms of sperm count and pregnancy rate. Thus far, based
      on more recent knowledge about the FSH receptor gene, the authors have correlated
      different polymorphisms of this gene with the outcome of FSH treatment. In this
      paper, the literature is reviewed and the authors' experience on using FSH in
      male infertility is discussed.

PMID- 18062864
TI  - Microarray detection of Y chromosome deletions associated with male infertility.
AB  - Array-comparative genomic hybridization (CGH) has emerged as a powerful new
      molecular tool for the high-resolution analysis of copy-number variation and
      breakpoint analysis. In this study, array-CGH was used to analyse known Yq
      deletions associated with male infertility. A microarray platform encompassing
      probes for chromosomes 13, 14, 21, X and Y was developed in-house and was used to
      detect different Yq deletion types. The successful application of this array for
      the detection of Yq deletions involving either the AZFb or AZFc region was
      demonstrated. Partial and complete AZF deletions were correctly detected in 13
      patients with Yq deletions previously identified by multiplex polymerase chain
      reaction (PCR). This study demonstrates that array-CGH may be an alternative
      approach to multiplex PCR for the diagnosis of known Yq deletions and potentially
      a useful tool for the discovery of other Y chromosome deletions/polymorphisms
      associated with defective spermatogenesis.

PMID- 18062865
TI  - Adenomyosis as a disorder of the early and late human reproductive period.
AB  - Magnetic resonance imaging (MRI) allows the diagnosis of adenomyosis in vivo with
      a high sensitivity and specificity. Usually the diagnosis of adenomyosis is
      obtained from women in their fourth to fifth decade of life. However, recent data
      suggest that adenomyosis may develop much sooner in life, particularly in women
      with endometriosis. In order to test these suggestions, MRI of the uterus in 227
      women with and without endometriosis was performed and the results were related
      to the age of the subjects (age groups: 17-24, 25-29, 30-34 and >34 years). The
      study revealed that the process of the development of adenomyosis, represented by
      an increased diameter of the dorsal junctional zone of the uterus as the imaging
      correlative of the invasion of basal endometrium into the junctional zone, had
      already commenced early in the third decade of life and progressed steadily
      during the fourth decade in women with endometriosis. Women without endometriosis
      showed almost no signs of adenomyosis up to the age of 34 years. Surprisingly,
      parallel in both groups of women, a marked increase in the incidence of
      adenomyosis could be observed beyond the age of 34 years, thus representing a
      common phenomenon in the age-related pathophysiological continuum of adenomyosis.

PMID- 18062866
TI  - Do uterine fibroids affect IVF outcomes?
AB  - The effect of myomectomy on implantation and pregnancy rates prior to assisted
      reproduction treatments is controversial. This study was designed to assess
      clinical outcomes of IVF cycles in women with uterine fibroids. A retrospective
      single-centre assessment of clinical outcomes of IVF/intracytoplasmic sperm
      injection (ICSI) treatments in infertile women in a 4-year span was carried out.
      All patients underwent detailed transvaginal ultrasound and hysteroscopy to
      precisely identify presence, location and intracavitary growth of uterine
      fibroids. Cumulative pregnancy, ongoing pregnancy and live birth rates were
      considered primary outcome measurements. Fifty-one women with fibroids (97
      treatment cycles), 63 patients with previous myomectomy (127 cycles), and 106
      infertile women who did not demonstrate fibroids anywhere in the uterus (215
      cycles) were considered for the analysis. No significant difference was found for
      pregnancy and live birth rates between groups. Women with fibroids>4 cm required
      an increased number of cycles to obtain an ongoing pregnancy, compared with the
      other groups. The data do not support pre-IVF myomectomy in women with small-to
      moderate uterine fibroids, regardless of their location. This represents valuable
      information in the counselling of women with fibroids before reproductive
      assisted cycles.

PMID- 18062868
TI  - Maintenance of the meiotic spindle during vitrification in human and mouse
      oocytes.
AB  - Vitrification appears to be a viable method for the cryopreservation of human
      metaphase II (MII) oocytes, but concerns regarding the concentration of
      cryoprotectants used during vitrification have been raised. In an attempt to
      circumvent this potential problem, the majority of protocols are carried out at
      room temperature. Exposing oocytes to temperatures below 37 degrees C, however,
      leads to rapid microtubule depolymerization. Polarized light microscopy was used
      to measure meiotic spindle retardance following exposure to cryoprotectants and
      vitrification in human and mouse oocytes. To quantify the extent of
      depolymerization, spindle retardance was determined before and after each
      treatment. Exposure to vitrification and warming solutions at room temperature
      (21-22 degrees C) caused the spindle of mouse MII oocytes to depolymerize. In
      contrast, no measurable changes in the meiotic spindle were detected by
      maintaining the temperature at 37 degrees C during the exposure regimen. By
      carrying out the entire vitrification and warming procedure at 37 degrees C, the
      spindle was also unaffected. Comparable results were obtained with vitrification
      of human MII oocytes at 37 degrees C. Analysis of sibling human oocytes
      demonstrated that slow freezing, in contrast to vitrification, was unable to
      preserve the meiotic spindle. Using a vitrification protocol employing 37 degrees
      C impacts negligibly on the meiotic spindle. Thus, fertilization can proceed
      without having to await spindle reformation.

PMID- 18062869
TI  - Single fresh and frozen-thawed blastocyst transfer using hyaluronan-rich transfer
      medium.
AB  - The purpose of this prospective randomized study was to evaluate use of a
      hyaluronan-rich transfer medium in fresh and frozen-thawed single blastocyst
      transfer. The study included 279 single blastocyst transfers in women aged<37
      years in their first, second or third treatment cycle. According to the type of
      single blastocyst transfer (fresh elective or frozen-thawed) the women were
      divided into two study and two control groups. In both study groups (n=130)
      transfers were performed using hyaluronan and in the control groups (n=149) a
      conventional transfer medium was used. The results indicate that fresh elective
      single blastocyst transfer with hyaluronan results in significantly higher
      pregnancy rates in a selected subgroup of women; those with >or=2 blastocysts
      developed to day 5 and a previous implantation failure (55% versus 10%; P=0.012).
      Overall pregnancy rates after fresh elective and frozen-thawed single blastocyst
      transfer were similar in both study and control groups.

PMID- 18062871
TI  - Comparative growth behaviour and characterization of stem cells from human
      Wharton's jelly.
AB  - Human embryonic stem cells (hESC) face ethical sensitivities and the problem of
      teratoma formation. Although Wharton's jelly stem cells (WJSC), also of embryonic
      origin, may not face such ethical concerns, it is not definitely known whether
      under hESC culture conditions they would be as pluripotent as hESC. WJSC grown on
      plastic showed two types of morphology (epithelioid and short fibroblastic) in
      primary culture depending on the culture medium used, and only fibroblastic
      morphology when passaged. When grown in the presence of hESC medium on mouse
      feeder cells, they produced atypical colonies containing hESC-like cells with
      high-nuclear cytoplasmic ratios and prominent nucleoli. They were positive for
      the hESC markers Tra-1-60, Tra-1-81, SSEA-1, SSEA-4, Oct-4 and alkaline
      phosphatase, negative for SSEA-3, showed normal karyotypes, developed embryoid
      body (EB)-like structures, did not produce teratomas in SCID mice and
      differentiated into neuronal derivatives. They were also positive for the
      mesenchymal CD markers (CD105, CD90, CD44), negative for CD34 and HLA, and
      although nine out of 10 embryonic stem cell genomic markers were detectable,
      these were expressed at low levels. WJSC are thus not as pluripotent as hESC but
      widely multipotent, and have the advantages of being able to be scaled up easily
      and not inducing teratomas.

PMID- 18062872
TI  - Current and future perspectives on intracytoplasmic sperm injection: a critical
      commentary.
AB  - Intracytoplasmic sperm injection (ICSI) is an increasingly popular means of
      treating infertility in couples who wish to conceive. However, there are many
      potential complications that can be faced by the clinician while performing ICSI.
      These complications and other related issues are discussed, with an emphasis on
      understanding how these issues are being resolved, or how they can be resolved in
      the future. Matters of sperm selection and injection are discussed, as well as
      the effect of ICSI on fertilization, embryonic growth and development, and the
      health of ICSI-conceived children. These aspects are viewed from various
      perspectives, including genetic, mechanistic, developmental and clinical. Since
      new studies on ICSI are published regularly, it is important that the established
      protocol is revised often, and that the role of ICSI in infertility therapy is
      continually re-evaluated.

PMID- 18062873
TI  - Basic aspects of implantation.
AB  - Implantation, a critical step for establishing pregnancy, requires molecular and
      cellular events resulting in healthy uterine growth and differentiation,
      blastocyst adhesion, invasion and placental formation. Successful implantation
      requires a receptive endometrium, a normal and functional embryo at the
      blastocyst stage and a synchronized dialogue between maternal and embryonic
      tissues. In addition to the main role of sex steroids, the complexity of embryo
      implantation and placentation is exemplified by the number of cytokines and
      growth factors with demonstrated roles in these processes. Disturbances of the
      normal expression and action of these cytokines result in absolute or partial
      failure of implantation and abnormal placental formation in mice and humans.
      Members of the gp130 cytokine family, interleukin (IL)-11 and leukaemia
      inhibitory factor, the transforming growth factor-beta superfamily, colony
      stimulating factors, and the IL-1 and IL-15 systems are all crucial for
      successful implantation. In addition, chemokines are important both in recruiting
      specific cohorts of leukocytes to the implantation site, and in trophoblast
      trafficking and differentiation. This review provides discussion on embryonic and
      uterine factors that are involved in the process of implantation in autocrine,
      paracrine and/or juxtacrine manners at hormonal, cellular, and molecular levels.

PMID- 18062875
TI  - Controversies in treatment of ectopic tubal pregnancy.

PMID- 18062876
TI  - [Construction of the recombinant adenovirus vector of interleukin-1 receptor II
      and its expression in eutopic stromal cells of endometriosis].
AB  - AIM: To develop a gene therapy vector of interleukin-1 receptor II(IL-1RII) with
      recombinant adenovirus and express IL-1RII in the eutopic stromal cells of
      endometriosis(EM). METHODS: Get full length of cDNA with IL-1RII gene was
      obtained by PCR. The gene was then subcloned into the pShuttle-CMV shuttle
      vector. The resultant plasmid (pShuttle-CMV-RII) was cotransduced into E.coli
      BJ5183 cells with pAdEasy-1 plasmid to undergo homologous recombination by
      electroporation. The linearized recombinant plasmid (pAd-RII) was transfected
      into 293 cells. The recombinant adenovirus was detected by examining the
      expression of IL-1RII while the recombinant adenovirus of LacZ gene was
      constructed as control. The stromal cells of EM were infected by the recombinant
      adenovirus and the expression of IL-1RII was detected by
      immunohistochemistry(IHC). RESULTS: It was confirmed by sequencing that the two
      ligand products had no mutation of IL-1RII. Restriction endonuclease analysis
      confirmed the successful cloning of the gene into the pShuttle-CMV and the
      recombinants(pAd-RII) were selected for kanamycin resistance. Presence of the
      recombinant adenovirus was confirmed by the X-gal stain of LacZ and the
      expression of soluble IL-1RII was detected by ELISA. IL-1RII was expressed in the
      stromal cells of EM by IHC. CONCLUSION: The recombinant adenovirus of IL-1RII has
      been successfully constructed and expressed in the stromal cells of EM, which
      provides a basis for the research into the role of IL-1RII and the effect of
      biological treatment in EM.

PMID- 18062877
TI  - [Expression of TRAIL gene eukaryotic expression vector modulated by the human
      telomerase reverse transcriptase gene core promoter in ovarian cancer cell line
      SKOV3].
AB  - AIM: To construct the TRAIL gene eukaryotic expression vector modulated by the
      human telomerase reverse transcription gene core promoter and to evaluate the
      expression of the TRAIL gene in ovarian cancer cell line SKOV3 in vitro. METHODS:
      The amplified TRAIL gene fragment was subsequently cloned into hTERT promoter
      pIRES2-EGFP vector and CMVpromoter-pIRES2-EGFP vector. The hTERT promoter-pIRES2
      EGFP-TRAIL and CMVpromoter-pIRES2-EGFP-TRAIL eukaryotic expression vectors were
      obtained, respectively. The plasmids were transfected into human ovarian
      carcinoma SKOV3 cell line by lipofeclin mediation and the positive clones were
      screened by G418. The expression of TRAIL gene was examined by RT-PCR, Western
      blot, immunocytochemistry and flow cytometry. RESULTS: All the constructed
      vectors were verified by enzyme digestion. The TRAIL gene of transfected cells
      was increased significantly (P<0.01). CONCLUSION: An eukaryotic expression vector
      of the TRAIL gene modulated by the human telomerase reverse transcription gene
      core promoter has been constructed successfully and its steady expression in
      human ovarian cancer cell line SKOV3, which will be beneficial to further
      research into its role in regulating the biological behavior of ovarian cancer
      cells.

PMID- 18062878
TI  - [Preliminary study of primarily cultured C57 articular cartilage transfected with
      plasmid IDO-EGFP by lipofectamine].
AB  - AIM: To determine the transfection efficiency and transient expression of pIDO
      EGFP gene in primarily cultured C57 articular cartilage of mice, and to establish
      a transfection method of the primarily cultured articular cartilage in mice.
      METHODS: Plasmid IDO-EGFP was amplified in Escherichia coli. The primarily
      cultured mouse chondrocytes which were initially obtained from articular
      cartilage were cultured in vitro and transfected with pIDO-EGFP by
      lipofectamine2000 reagent under optimized condition. Transfection process and
      transient expression were evaluated by fluorescent microscopy and laser scanning
      confocal microscopy (LSCM), and transfection efficiency was determined by flow
      cytometry. RESULTS: There was obvious expression of EGFP at 24 h after
      transfection. The transfection efficiency of pIDO-EGFP into primarily cultured
      mouse chondrocytes reached 36.43% at 48 hours and the transfection did not affect
      the process of cell adherence. CONCLUSION: IDO gene has been successfully
      transfected into primarily cultured chondrocytes by means of lipofectamine2000
      reagent and the chondrocytes can survive in vitro. Satisfactory efficiency of
      transient transfection can be reached under optimized condition, which will
      provide a basis for gene introduction and modification of tissue engineered
      cartilage.

PMID- 18062879
TI  - [Effect of LIPUS on the cellular behavior of human primary macrophages].
AB  - AIM: To explore the effect of low intensity pulsed ultrasound (LIPUS) on the
      biological behavior of macrophages to provide some theoretical foundations for
      its clinical application. METHODS: Human primary macrophages were obtained by
      using modified Ficoll-paque density gradient centrifugation combined with
      adherent method. The phagocytosis of macrophages was analyzed using fluorescein
      labelled E.coli. The expression of the secreted proteins was determined by
      proteins array and the secretion of metalloproteinases (MMPs) was examined by
      gelatin zymography. The focal complexes and extracellular matrix
      metalloproteinase inducer (CD147) were detected by fluorescence microscopy and
      the phosphorylation of Src and ERKs was examined by Western blot. RESULTS: The
      human primary macrophages were successfully isolated and cultured in vitro. LIPUS
      accelerated the macrophages to phagocytose E.coli, promoted the protein
      expression of CD147 and MMPs, increased the level of protein tyrosine
      phosphorylation, and induced the formation of focal complexes and the
      phosphorylation of Src and ERKs. CONCLUSION: LIPUS may up-regulate the
      phagocytosis and secretion of human primary macrophages through the activation of
      Src and ERKs.

PMID- 18062880
TI  - [Construction of an expression vector for high expression of siRNA].
AB  - AIM: To construct the vector for efficient expression of siRNA using pre-mir30
      backbone. METHODS: By chemical synthesis method, pre-mir30 backbone introduced an
      appropriate restriction enzyme site for foreign shRNA inserting was cloned into
      an expressing vector containing U6 promoter. The silencing efficiency of a new
      siRNA expressing vector was detected by transfection and Western blot. RESULTS:
      The new vector containing pre-mir30 backbone expressing siRNA against GFP could
      markedly inhibit the expression of GFP compared with the vector expressing
      control siRNA. CONCLUSION: siRNA expressing vector constructed by pre-mir30
      backbone could highly express foreign siRNA.

PMID- 18062881
TI  - [Isolation of exosomes derived from dendritic cells by ultrafiltration
      centrifugalization and their morphologic characteristics].
AB  - AIM: To investigate a method for isolating exosomes by ultrafiltration
      centrifugalization based on their physical size and density so as to advance
      traditional method and promote recovery rate. METHODS: The culture supernatant of
      murine dendritic cells line (DC2.4) was collected and clarified through a hollow
      fiber cartridge to remove cells and their debris. The clarified supernatant was
      concentrated by Amicon ultrafiltration tube and then the concentrated supernatant
      was purified when loaded into density gradient centrifugation to obtain the DC
      Ex. The traditional differential centrifugation method was used in control group.
      Transmission electron microscope (TEM) was used to identify the morphology of the
      two products. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE) and Western blot were employed to analyze their proteins. RESULTS: The
      obtained pellets possessed the features of dendritic cell exosomes described in
      previous literature, including morphology and SDS-PAGE profile. Moreover,these
      particles contained characteristic molecular markers MHC class I, MHC class II,
      CD80 and CD86. Compared with the differential centrifugation method,
      ultrafiltration centrifugalization technique is a shorter and more producible
      process resulting in production being highly purified. CONCLUSION:
      Ultrafiltration centrifugalization technique is a convenient and useful method
      for DC-Ex isolation.

PMID- 18062882
TI  - [Effects on T cell proliferation by culture supernatant of fibroblast cells
      modified with mIDO gene].
AB  - AIM: To investigate the effects on T cell proliferation by culture supernatant of
      fibroblast cells modified by mIDO gene. METHODS: Eukaryotic expression plasmid
      pEGFP-Nl-mlDO was transfected into the mouse fibroblast cell lines by liposome.
      The concentration of tryptophan in pEGFP-Nl-mIDO fibroblast cell culture medium
      was tested. The effects on ConA-stimulated T cells, proliferation by pEGFP-Nl
      mlDO fibroblast cell culture medium were analyzed by CFSE technique. RESULTS:
      pEGFP-N1-mlDO was transfected into the fibroblasts cell lines successfully.
      Tryptophan in pEGFP-Nl-mIDO-transfected-fibroblast cell culture medium was
      undetectable, which showed pEGFP-Nl-mIDO-transfected-fibroblast cells produced
      active mIDO, resulting in the degradation of tryptophan in the medium. mIDO could
      inhibit proliferation of ConA-stimulated T cells, which was marked by CFSE.
      CONCLUSION: T cell proliferation can be inhibited by the fibroblast cells
      modified by mIDO gene.

PMID- 18062883
TI  - [Effect of seleno-arginine on cellular immunological function in D-gal aging
      mice].
AB  - AIM: To study the effect of seleno-argnine on cellular immunological function in
      D-gal aging mice. METHODS: The mice were divided into normal group, model group,
      low seleno-argnine group(L-SeArg) and high seleno-argnine group (H-SeArg). D
      galactose induced aging model was set up by s.c. injection for 42 days, i.g.
      method was used to add Seleno-argnine. Spleen index(SI) and thymus index (TI)
      were measured. The ability of Spleen cell multiplication and NK cell killing
      activity were determined by MTT colorimetry. The changes of CD40 and CD40L
      expression were observed by immunofluorescent assay. RESULTS: Compared with the
      model mice, seleno-argnine increased spleen index and thynus index, enhanced the
      ability of spleen cell multiplication, enhanced the expression of CD40 and CD40L,
      and accelerated the NK cell killing activity. Between the two seleno-argnine
      groups, the effect of L-SeArg on cellular immunological function was more obvious
      in D-gal aging mice.The result were statistic ally significantly compared with
      the model mice(P<0.01). CONCLUSION: D-gal injection can decrease the cellular
      immunological function of mice. Seleno-argnine can activate immune cells, enhance
      the cellular immunological function of mice, reduce the toxic effect of D-gal and
      delay the aging process.

PMID- 18062884
TI  - [Expression of recombinant mouse IL-1beta significantly down-regulates NK cell
      mediated cytolysis [corrected] against H22 hepatoma cells].
AB  - AIM: To investigate the effect of the expression of recombinant IL-1beta in H22
      hepatoma cells on its response to NK cell mediated cytotoxicity. METHODS: BALB/c
      mouse was stimulated by 6% of starch. Total RNA was prepared from peripheral
      blood monocytes (PBMCs). IL-1beta gene (843 bp) was obtained by RT-PCR. The
      purified PCR product digested by Xho I and EcoR I was cloned into pIRES2-EGFP to
      construct the recombinant pIRES2-EGFP-mIL-1beta expression vector which was
      verified by PCR, restriction enzyme assay (Xho I and EcoR I) and DNA sequencing.
      Then the purified pIRES2-EGFP-mIL-1beta plasmid was transfected into H22 hepatoma
      cells by jetPEI. The expression level of recombinant IL-1beta was detected by RT
      PCR and confocal microscopy. The cytotoxicity of wild-type spleenic NK cells
      against H22 cells was assessed by MTT assay. RESULTS: After the total RNA
      isolated from the starch stimulated BALB/c mouse PBMC, 843 bp IL-1beta gene in
      length was prepared by RT-PCR. The purified PCR product digested by EcoR I and
      Xho I was ligated by pIRES2-EGFP to create pIRES2-EGFP-mIL-1beta expression
      plasmid which was verified by PCR, restriction enzyme assay and DNA sequencing.
      Then pIRES2-EGFP-mIL-1beta was transfected into H22 hepatoma cells by jetPEI. RT
      PCR and confocal microscopy assay showed these cells expressed high level of
      recombinant IL-1beta expression vector. In a 4-hour based MTT assay, IL-1beta in
      H22 cells was more resistant to NK92 cell mediated cytotoxicity compared with the
      cells transfected with pIRES2-EGFP. Meanwhile, the cytolytic capacity of the
      spleenic NK cells separated from wild-type mouse decreased about 10% when the
      ratio of effector to target was 40:1. CONCLUSION: The expression of
      proinflammatory cytokine IL-1beta can significantly down-regulate the cytolytic
      activity of NK cells against H22 hepatoma cells. It plays a crucial role in the
      immune escape of hepatoma from NK cell mediated innate immunity.

PMID- 18062885
TI  - [Expression of HCV NS5A gene in HepG2 cell and the effect of the NS5A expression
      on PI3K in vitro].
AB  - AIM: To reveal the influence of HCV-NS5A on PI3K, we probe into the relationship
      between NS5A and PI3K in vitro. METHODS: Full length NS5A gene of HCV was
      amplified by PCR, using the plasmid containing HCV full-length open reading frame
      (ORF) as template, and cloned into the eukaryotic expressing plasmid pcDNA3.0(-)
      by DNA recombination technique. The recombinant vector was identified by
      digestion with restriction enzymes and polymerase chain reaction and by directly
      sequencing. Then both the recombinant vector pcDNA3.0(-)-NS5A and the control
      vector pcDNA3.0(-) were transfected HepG2 cell using Lipofectamin2000. RESULTS:
      Expressing NS5A was proven by RT-PCR and Western blot analysis in transfected
      HepG2 cell. Further more we examined the PI3K protein expressed in the HepG2 cell
      expressing recombinant NS5A. CONCLUSION: NS5A can activate PI3K in vitro and its
      signal cascade pathway.

PMID- 18062886
TI  - [Expression and preliminary applications of hepatitis B surface antigen mutants].
AB  - AIM: To clone and express HBsAg mutant in the Pichia pastoris. METHODS: The
      cloned wild type pGAP-S was used as the DNA template to generate mutant type pGAP
      MS with a single or double nucleotide changes incorporated in complementary
      oligonucleotide primers. The product was linearized with BspH I and transformed
      into Pichia pastoris strain GS115, and stable multicopy integrants were screened
      in medium containing different concentrations of Zeocin. RESULTS: The pGAP-MS
      expression vector was successfully constructed and stable numbers integrated
      strains with high copy number were obtained. The expression of HBsAg mutant
      protein was identified by SDS-PAGE and Western blot with specific polyclonal
      antibody. The molecular weight of recombinant HBsAg mutant was 38 kDa. AxSYM
      HBsAg V2(Abbott)assays demonstrated all 10 HBsAg mutants were reactive.
      CONCLUSION: The recombinant HBsAg mutant with immunoreactivity was successfully
      expressed in Pichia pastoris, and it was of practical value on the quality
      control and clinical applications of commercial assays.

PMID- 18062887
TI  - [Construction and expression of eukaryotic expression vector of a novel apoptosis
      related mouse gene, mPNAS-4 and its antitumor activity in vitro].
AB  - AIM: To construct eukaryotic vector of a novel apoptosis-related gene from mouse
      (mPNAS-4) and overexpress it in mouse Lewis lung carcinoma(LL2) cell line. To
      explore the apoptosis of the tumor cells induced by overexpressed mPNAS-4 in LL2
      cells via transfection. METHODS: RT-PCR was applied to amplify the encoding
      region of mPNAS-4 gene from the mouse liver. The cDNA was cloned into the
      eukaryotic expression vector pcDNA3.1(+) and the resulting recombinant expression
      plasmid pcDNA3.1(+)-mPNAS-4 was then transfected into mouse Lewis lung carcinoma
      (LL2) cells through Lipofectamine 2000. Overexpression of mPNAS-4 in the
      transfected cells and proliferation of the transfected cells was detected by RT
      PCR and MTT assay,respectively, while the apoptosis was analysed by FCM and DNA
      ladder. RESULTS: The recombinant eukaryotic expression vector pcDNA3.1(+)-mPNAS-4
      was successfully constructed.The expression of mPNAS-4 at the mRNA level in LL2
      cells transfected with pcDNA3.1(+)-mPNAS-4 was up-regulated significantly. The
      proliferation of LL2 cells was inhibited. CONCLUSION: Overexpression of mPNAS-4
      may have apoptotic effects and therefore inhibit the proliferation of LL2 cells.

PMID- 18062888
TI  - [Expression of anti-HIV envelope glycoprotein scFv in Pichia pastoris and its
      biologic activities analysis].
AB  - AIM: To construct the vector and express anti-HIV-1 envelope glycoprotein single
      chain Fv fragment in Pichia pastoris. METHODS: The target gene was digested from
      plasmid pET28-scFv and cloned into pichia pastoris vector via gene engineering
      and DNA recombination techniques. The recombinant plasmid was linearized and
      transferred into Pichia pastoris strains GS115 by electroporation. After positive
      recombinant was selected and expression was induced by methanol, the target
      protein was analyzed by RT-PCR, SDS-PAGE and double-antibody sandwich ELISA.
      RESULTS: High copies of transformant were obtained by phenotype determining and
      PCR amplification. RT-PCR and SDS-PAGE demonstrated the target protein was
      successfully expressed. And the yield account for about 18 percent of the total
      cell proteins. Double-antibody sandwich ELISA analysis proved that the
      recombinant scFv had good biological activities since it could be recognized and
      induce special immune respond with gp120 antigen. CONCLUSION: The scFv was
      expressed successfully. This research will lay the foundation for AIDS target
      therapy and further study of anti-HIV activities.

PMID- 18062889
TI  - [Construction, expression and functional characterization of single chain
      variable fragments (scFv) against human CD33 antigen].
AB  - AIM: To construct and express the single chain variable fragments (scFv) gene
      against human CD33 antigen, and characterize its bioactivity. METHODS: The genes
      encoding the light and heavy chain variable regions were cloned by RT-PCR from a
      murine hybridoma cell line, which could produce monoclonal antibody(mAb) against
      human CD33 antigen. Then the light and heavy chain variable regions were fused
      together by a short peptide linker containing 15 amino acid (Gly(4)Ser)(3) using
      splice-overlap extensive PCR. The recombinant anti-CD33 scFv was subcloned into
      the expression vector pET28a(+) and expressed in E.coli Rosetta after induction
      by IPTG. RESULTS: SDS-PAGE and Western blot analysis showed that the recombinant
      anti-CD33 scFv gene was expressed in the form of inclusion body in E.coli
      Rosetta, and the purified fusion protein was obtained after a series of
      purification steps including cell lysis, inclusion body solubilization, Ni(2+)
      metal affinity chromatography and protein refolding. Flow cytometry(FCM) analysis
      showed that the scFv could react with human CD33 antigen. CONCLUSION: Recombinant
      anti-CD33 scFv gene has been successfully constructed and expressed in E.coli
      Rosetta, which could provide foundation for the future target therapy to the
      myeloid leukemia.

PMID- 18062890
TI  - [Cloning of the variable region genes from hybridoma against bFGF and expression
      of single chain antibody fragments in E.coli HB2151].
AB  - AIM: To construct and express the single chain antibody (scFv) in E.coli HB2151
      by cloning the variable region genes from hybridoma against bFGF. METHODS: Total
      RNA was extracted from hybridoma cell line B2F3 secreting mAbs against bFGF and
      the cDNA was amplified by retropolymerase chain reaction (RT-PCR). V(L) and V(H)
      were fused by a short peptide linker containing 15 amino acids (Gly(4)Ser)(3)
      using splice-overlap extension PCR to construct the scFv gene. The sequences of
      the scFv were analyzed by Shanghai Sangon Biological Engineering Technology and
      Services Co. Ltd and Ig Blast data base in GenBank. The scFv gene was inserted
      into pCANTAB-5E vector and expressed in E.coli HB2151. RESULTS: The V(H) gene
      contained 375 base pairs and encoded 125 amine acid residues. The V(L) gene
      contained 399 base pairs and encoded 133 amine acid residues. There were four
      FRs, three CDRs and two characteristic cysteine residues in the V(H) gene and the
      V(L) gene, respectively. The scFv gene contained 789 base pairs and encoded 263
      amine acid residues with the structure of V(H)-linker-V(L). Restriction
      endonuclease digestion and DNA sequencing proved that the expression vector of
      pCANTAB-5E-scFv was constructed correctly. SDS-PAGE and ELISA analysis showed
      that scFv was successfully expressed in E.coli HB2151 and the expression protein
      had specific antigen binding activity. CONCLUSION: The variable region genes of
      anti-bFGF mAbs have been cloned successfully and single chain antibody fragments
      have been constructed and expressed, which will be a great help to the study of
      humanized antibodies against bFGF.

PMID- 18062891
TI  - [Construction of prophylactic recombinant HPV58-attenuated Shigella vector live
      vaccine and evaluation of its protective efficacy and immunogenicity in the
      guinea pig keratoconjunctivitis model].
AB  - AIM: To construct the prophylactic recombinant HPV58-attenuated Shigella vector
      live vaccine and evaluate its protective efficacy and immunogenicity in the
      Guinea pig Keratoconjunctivitis model. METHODS: The HPV58 L1 gene was cloned into
      PUCMT, and the recombinant plasmid HPV58 L1-pCVD442 was constructed and
      introduced into attenuated Shigella (Sf301: deltavirG) with helper plasmid
      PRK2013 by filter mating. After homologous recombination, the positive colonies
      in Sf301: deltavirG strains contained HPV58L1 gene were selected and verified by
      PCR. The expressed HPV58L1 protein was harvested and analyzed by SDS-PAGE and
      Western blot. The bio-activity of the interested protein was identified by mouse
      erythrocyte hemagglutination assay, and the VLP formation was proved with
      transmission electron microscope. Guinea pig Keratoconjunctivitis model was used
      to evaluate protective efficacy and immunogenicity of the vaccine. 20 days after
      immunization, serum HPV58L1-IgG, IgA level and serum sf301 LPS- IgG, IgA level
      were measured by ELISA, and HPV58 L1-specific IgA-ASC and IgG-ASC of spleen and
      lymph nodes (SVCLN, MDLN, MSLN and pp) were measured by ELISPOT assay. RESULTS:
      HPV58 L1 protein with MW 60 kDa was confirmed by Western blot. The ability of the
      interested protein to self-assemble into VLPs was identified by transmission
      electron microscope, and the result of murine erythrocyte hemagglutination assay
      indicated that the given proteins expressed by the recombinant bacillus had
      similar characteristics as the natural HPV58L1 protein.In the Guinea pig
      Keratoconjunctivitis Model, animal immune results showed that there were no
      Keratoconjunctivitis occurred in the immune group(HPV58-attenuated Shigella), and
      after Sf301 attacking, 80% eyes had no Keratoconjunctivitis occurrence. 20 days
      after immunization, serum HPV58L1-IgG, IgA level were obviously increased; but
      serum sf301 LPS-IgG position was just slightly increased; ELISPOT results showed
      that HPV58 L1-specific IgA-ASC and IgG-ASC of spleen and lymph nodes were also
      obviously increased. CONCLUSION: Recombinant HPV58L1-attenuated Shigella vector
      live vaccine could induce strong humoral immune responses in the immunized
      animals.

PMID- 18062892
TI  - [The functional mechanism of CIK cells on ovarian carcinoma cell lines
      SKOV3/CDDP].
AB  - AIM: To investigate the functional mechanism of CIK cells or ovarian carcinoma
      cell lines SKOV3/CDDP. METHODS: The changes of ultramicrostructure, cell cycle,
      apoptosis, expression of multidrug resistance-associated protein (MDR1, Topo
      IIbeta) and other molecules (hB7-1, hB7-2, MHCIb, HLA-DR) of SKOV3/CDDP cells
      treated with or without CIK cells were detected by electron microscope, MTT and
      FCM. The changes of cytokine (IL-2, TNF-alpha, IFN-gamma, GM-CSF) in sera of SCID
      mice bearing SKOV3/CDDP cells were detected by radioimmunit and ELISA. RESULTS:
      CIK cells could induce apoptosis of the SKOV3/CDDP cells by electronmicroscopic
      observations. The apoptosis rate in CIK group was 9.07%, and its cell cycle was
      arrested at S and G2/M phase (P<0.05). Compared with NS Group, the co-expression
      of MDR-1 and Topo-IIbeta were decreased significantly in the CIK treated
      group(P<0.05), and the expression of MHCIb, HLA-DR, hB7-1 and hB7-2 antigen were
      increased significantly (P<0.01). Compared with NS Group, the contents of IL-2,
      TNF-alpha, INF-gamma, GM-CSF were increased significantly (P<0.01) in SCID mice
      of CIK group. CONCLUSION: CIK cells have several important biological effects on
      the ovarian carcinoma cell line SKOV3/CDDP, which may lay the foundation for
      further research on anti-tumor therapy.

PMID- 18062893
TI  - Biomarkers of acute kidney injury: early diagnosis, pathogenesis, and recovery.
AB  - This review article represents the proceedings from the translational research
      symposium presented at the Federation of American Societies for Experimental
      Biology/American Federation for Medical Research (FASEB/AFMR) meeting in May 2007
      in Washington, DC. This research symposium consisted of four talks, which are
      individually summarized below. The first talk gave a general overview of the
      biomarkers in the setting of acute kidney injury (AKI), along with some data from
      clinical biomarker studies. The second talk discussed the preclinical studies of
      the emerging biomarkers in the area of AKI. The third talk discussed the
      biomarkers of AKI after deceased kidney transplantation, which is a unique model
      of kidney ischemia-reperfusion injury. The final talk discussed the role of
      circulating stem cells in renal tubule regeneration after ischemic injury and if
      they have potential for biomarkers of recovery or therapeutic intervention.

PMID- 18062896
TI  - Intracardiac and intrarenal renin-angiotensin systems: mechanisms of
      cardiovascular and renal effects.
AB  - The renin-angiotensin system (RAS) is a hormonal system that controls body fluid
      volume, blood pressure, and cardiovascular function in both health and disease.
      Various tissues, including the heart and kidneys, possess individual locally
      regulated RASs. In each RAS, the substrate protein angiotensinogen is cleaved by
      the peptidases renin and angiotensin-converting enzyme to form the biologically
      active product angiotensin II, which acts as an intracrine cardiac and renal
      hormone. The components of each RAS, including aldosterone (ALDO), may be
      produced locally and/or may be delivered by or sequestered from the circulation.
      Overactivity of the cardiac RAS has been associated with cardiac diseases,
      including cardiac hypertrophy due to volume and/or pressure overload, heart
      failure, coronary artery disease with myocardial infarction, and hypertension.
      Overactivity of the renal RAS has been associated with various kidney diseases,
      including nephropathies and renal artery stenosis. The principal effects of an
      overactive RAS include the generation of reactive oxygen species, which leads to
      "oxidative stress," activation of the nuclear transcription factor kappaB, and
      stimulation of pathways and genes that promote vasoconstriction, endothelial
      dysfunction, cell hypertrophy, fibroblast proliferation, inflammation, excess
      extracellular matrix deposition, atherosclerosis, and thrombosis. It has been
      suggested that oxidative stress is the central mechanism underlying the
      pathogenesis of RAS-related and ALDO-related chronic cardiovascular and renal
      tissue injury and of cardiac arrhythmias and conduction disturbances.

PMID- 18062897
TI  - Acetylcholinesterase activity in veterans of the first Gulf War.
AB  - BACKGROUND: Factors affecting acetylcholine-mediated neurotransmission have been
      proposed as possible explanations for physical and mental health symptoms among
      veterans of the 1990-1991 Gulf War. This study was designed to examine
      relationships of deployment to the Gulf, as well as symptoms after military
      service, with postdeployment activity of acetylcholinesterase (AChE) and related
      enzymes. METHODS: The patient population included 488 veterans, originally from
      Iowa at enlistment, who served in the US military during August 1990 to July
      1991. Demographic, military, and clinical characteristics were obtained from a
      population-based cohort study (in 1995-1996) and from a nested case-control study
      (in 1999-2002). Stored serum samples (from the 1999-2002 assessment) were
      analyzed for activity of AChE and related enzymes. These two data sources were
      merged, and multiple linear regression models estimated the association of
      deployment, stress (anxiety) or mood disorders, and symptoms compatible with Gulf
      War veterans' illnesses (GWVIs), with enzyme activity. RESULTS: Seventy-four
      percent (n = 361) of veterans had been deployed to the Gulf. At the time of
      evaluation, 23% (n = 113) of participants reported anxiety and 15% (n = 71)
      reported mood disorders; 49% (n = 171 of 347 eligible veterans) had symptoms of
      GWVIs, and the median AChE activity was 839 units. AChE activity was similar for
      compared groups across all categories, including an adjusted difference of -27
      units (p = .50) for deployed versus nondeployed veterans and 87 units (p = .13)
      for veterans with versus without symptoms of GWVIs. CONCLUSIONS: Neither
      deployment to the Gulf nor symptoms compatible with GWVIs are associated with
      long-term serum AChE activity.

PMID- 18062898
TI  - Attenuation of signaling and nitric oxide production following prolonged leptin
      exposure in human aortic endothelial cells.
AB  - Acute leptin exposure stimulates endothelial nitric oxide (NO) production in
      vitro. In contrast, chronic elevations in circulating leptin levels in patients
      with obesity are associated with endothelial dysfunction and impaired endothelial
      NO production. Therefore, the goal of the current study was to examine the direct
      effects of acute and more sustained leptin stimulation on endothelial nitric
      oxide synthase (eNOS) and NO production in human aortic endothelial cells
      (HAECs). HAECs were treated with vehicle or with leptin (5 or 60 ng/mL) acutely
      (30-60 minutes) or for 72 hours. HAEC NO release into culture media was measured
      with a chemiluminescence technique, and superoxide (O(2)(-.)) production was
      measured with electron spin resonance (ESR) spectroscopy. HAEC eNOS activity was
      measured as the conversion of (3)H-arginine to (3)H-citrulline, and protein
      levels of eNOS, phospho-eNOS (serine 1177), Erk, phospho-Erk, suppressor of
      cytokine signaling (SOCS3), xanthine oxidase (XO), and the reduced nicotinamide
      adenine dinucleotide (NADPH) oxidase components p22phox, p67phox, Nox-4, and
      gp91phox were examined by Western blotting or immunoprecipitation. Acute leptin
      exposure increased eNOS serine 1177 phosphorylation and caused Erk activation. In
      contrast, prolonged leptin stimulation was not cytotoxic and failed to alter eNOS
      expression, phosphorylation, or HAEC NO release. Furthermore, prolonged leptin
      stimulation did not alter O(2)(-.) production or NADPH oxidase or XO expression
      but increased SOCS3 expression. In contrast to acute stimulation, prolonged (72
      hours) stimulation does not alter endothelial cell NO or O(2)(-.) production. We
      postulate that chronic leptin stimulation, through increased SOCS3 expression,
      may attenuate the effects of leptin on vascular endothelial function.

PMID- 18062899
TI  - Adenosine promotion of cellular migration in bronchial epithelial cells is
      mediated by the activation of cyclic adenosine monophosphate-dependent protein
      kinase A.
AB  - Migration of neighboring cells into the injury is important for rapid repair of
      damaged airway epithelium. We previously reported that activation of the A(2A
      )receptors (A(2A)ARs) mediates adenosine-stimulated epithelial wound healing,
      suggesting a role for adenosine in migration. Because A(2A)AR increases cyclic
      adenosine monophosphate (cAMP) levels in many cells, we hypothesized that cAMP
      dependent protein kinase A (PKA) is involved in adenosine-mediated cellular
      migration. To test this hypothesis, we stimulated a human bronchial epithelial
      cell line with adenosine and/or A(2A)AR agonist (5'-(N-cyclopropyl)-carboxamido
      adenosine [CPCA]) in the presence or absence of adenosine deaminase inhibitor
      (erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride [EHNA]). Cells treated with
      adenosine or CPCA demonstrated a concentration-dependent increase in migration.
      Similar results were observed in the presence and absence of EHNA. To confirm
      A(2A) involvement, we pretreated the cells for 1 hour with the A(2A) receptor
      antagonist ZM241385 and then stimulated them with either adenosine or CPCA. To
      elucidate PKA's role, cells were pretreated for 1 hour with either a PKA
      inhibitor (KT5720) or a cAMP antagonist analogue (Rp-cAMPS) and then stimulated
      with adenosine and/or CPCA. Pretreatment with KT5720 or Rp-cAMPS resulted in a
      significant decrease in adenosine-mediated cellular migration. PKA activity
      confirmed that bronchial epithelial migration requires cAMP and PKA activity.
      When cells were wounded and stimulated with CPCA, an increase in PKA activity
      occurred. Pretreatment for 1 hour with either KT5720 or Rp-cAMPS resulted in a
      significant decrease in adenosine-mediated PKA activation. These data suggest
      that adenosine activation of A(2A)AR augments epithelial repair by increasing
      airway cellular migration by PKA-dependent mechanisms.

PMID- 18062901
TI  - Effects of levosimendan on coronary artery flow and cardiac performance in
      patients with advanced heart failure.
AB  - BACKGROUND: Levosimendan has inotropic and vasodilatory effects. We investigated
      the effects of levosimendan on coronary flow and associated changes in
      neurohormonal activation and cardiac performance in patients with advanced heart
      failure. METHODS: Forty-two patients with NYHA III-IV and a left ventricular
      ejection fraction (EF) 25+/-6%, were randomised to levosimendan 0.1 microg/kg/min
      (n=21) or placebo for 24 h. Before and 24 h after each treatment, we assessed:
      the maximal velocity (Vmax), time integral (VTI) and deceleration time (DT) of
      the diastolic coronary flow wave (CF) in LAD using transthoracic Doppler
      echocardiography, pulmonary artery systolic pressure by Doppler echocardiography,
      E/E' ratio using Doppler imaging of mitral inflow velocity, tissue Doppler
      imaging of the mitral annulus and B-type natriuretic peptide (BNP) levels.
      RESULTS: By ANOVA, there was a greater increase in CF-Vmax (43+/-23 vs.25+/-8
      cm/s), CF-DT (904+/-250 vs. 667+/-151 ms), and EF and a greater decrease in BNP,
      pulmonary artery systolic pressure and E/E? after levosimendan than after placebo
      (p<0.05). Compared to baseline, the percent changes in CF-VTI were related to the
      concomitant changes in EF, E/E?, and BNP after treatment with levosimendan
      (r=0.69, r=?0.51 and r=?0.80, p<0.05 respectively). CONCLUSION: Treatment with
      levosimendan improves coronary flow and microcirculation in parallel with an
      improvement in cardiac performance and neurohormonal activation in patients with
      advanced heart failure.

PMID- 18062902
TI  - Value of BNP to estimate cardiac risk in patients on cardioactive treatment in
      primary care.
AB  - Cardiac dysfunction may be suspected in patients with cardiovascular disease but
      identifying those with the highest risk is problematic. B-type natriuretic
      peptide (BNP) is a strong marker of heart failure in un-treated patients. This
      study evaluates a combined BNP and clinical algorithm for detecting cardiac
      dysfunction and the risk of death, in patients receiving cardioactive medication.
      METHODS: 459 stable general practice patients, who were taking typical heart
      failure drugs for any indication, were included. Echocardiography, ECG, and assay
      of NT-proANP and BNP (two methods) were performed. Regression models were used to
      identify items in a Risk Score to detect cardiac dysfunction. RESULTS: A Risk
      Score based on history of myocardial infarction (1 point), abnormal ECG (2
      points), atrial fibrillation (1 point) and raised BNP (1-2 points) detected
      cardiac dysfunction with an AUC of ROC of 0.85. A Risk Score > or = 2 had a
      sensitivity of 90%, specificity of 58%, and positive and negative predictive
      values of 37% and 96%. Risk Score and LVEF<0.36 also predicted mortality.
      Abnormal BNP defined as either >100 pg/ml (Shionogi), or as age and sex related
      values, had similar predictive value. CONCLUSION: In patients on cardioactive
      medication, a structured Risk Score based on raised BNP, history of MI, atrial
      fibrillation and abnormal ECG was useful for identifying patients for immediate
      further examination and those who could be evaluated later.

PMID- 18062904
TI  - The thymus as a target for mycobacterial infections.
AB  - Mycobacterial infections are among the major health threats worldwide. Ability to
      fight these infections depends on the host's immune response, particularly on
      macrophages and T lymphocytes produced by the thymus. Using the mouse as a model,
      and two different routes of infection (aerogenic or intravenous), we show that
      the thymus is consistently colonized by Mycobacterium tuberculosis, Mycobacterium
      avium or Mycobacterium bovis BCG. When compared to organs such as the liver and
      spleen, the bacterial load reaches a plateau at later time-points after
      infection. Moreover, in contrast with organs such as the spleen and the lung no
      granuloma were found in the thymus of mice infected with M. tuberculosis or M.
      avium. Since T cell differentiation depends, to a large extent, on the antigens
      encountered within the thymus, infection of this organ might alter the host's
      immune response to infection. Therefore, from now on, the thymus should be
      considered in studies addressing the immune response to mycobacterial infection.

PMID- 18062906
TI  - The Mx GTPase family of interferon-induced antiviral proteins.
AB  - Mx proteins are interferon-induced members of the dynamin superfamily of large
      GTPases. They inhibit a wide range of viruses by blocking an early stage of the
      replication cycle. Studies in genetically defined mouse strains highlight their
      powerful action in early antiviral host defence.

PMID- 18062905
TI  - Visualization of Mycobacterium avium in Crohn's tissue by oil-immersion
      microscopy.
AB  - Studies seeking Mycobacterium avium subsp. paratuberculosis in Crohn's disease by
      PCR have generated inconsistent findings. As an alternative, microscopy offers a
      number of advantages, including direct visualization of organisms in tissue.
      Experimental infections have demonstrated that M. avium organisms can be seen by
      both acid-fast staining and species-specific in situ hybridization, but because
      they are smaller than M. tuberculosis, oil-immersion microscopy (x 1,000
      magnification) is needed. We performed a blinded search for M. avium in paraffin
      embedded surgical resections from Crohn's and control subjects at two centres.
      Specimens were coded and subjected to acid-fast staining and ribosomal RNA in
      situ hybridization for M. avium rRNA. Agreement between these two methods was
      good (42/52 patients, kappa=0.60) and similar results were observed for patients
      from two centers. Together, both methods provided positive results in 10 of 17
      Crohn's subjects (59%, 95% CI: 36-78), contrasting with only 5 of 35 control
      subjects (Odds ratio for Crohn's vs. controls=8.6, p=0.002). M. avium organisms
      had an intracellular localization within inflammatory lesions, but were often
      observed as lone organisms outside of granulomas. Using two assays in two
      settings, presence of M. avium organisms was strongly associated with Crohn's
      disease.

PMID- 18062907
TI  - Characterization of the chicken CD200 receptor family.
AB  - The modulation of myeloid cells via inhibitory and activating immunoglobulin
      superfamily members has been a subject of intense study in mammals. One such
      example is the inhibitory receptor for CD200, which is shown to regulate the
      activation threshold of myeloid cells by interaction with the broadly distributed
      CD200 molecule. By looking at sequence homology and synteny conservation in the
      chicken genome, we identified two members of the CD200 receptor family in chicken
      on chromosome one. Cloning and further characterization of the protein sequence
      yielded a potentially inhibitory ggCD200R-B1 with a splice variant lacking a
      transmembrane region and a potentially soluble ggCD200R-S1. Both showed a typical
      V/C2-set Ig domain arrangement and we present evidence that these two genes have
      evolved by gene duplication. The inhibitory receptor displayed an uncharged
      transmembrane region and a long cytoplasmic tail encoding four tyrosine residues,
      one of them embedded in a motif similar to the mammalian NPxY motif. Further
      characterization of ggCD200R-B1 showed that it is expressed as a highly
      glycosylated protein and that its cytoplasmic tyrosine residues can be
      phosphorylated. Real-time RT-PCR analysis of various tissues and primary cells
      showed that ggCD200R-B1 is predominantly expressed in macrophages, whereas
      ggCD200R-S1 is highly expressed in peripheral blood mononuclear cells, but not
      macrophages. In summary, we showed that there is a homologue of mammalian CD200R
      conserved in chicken suggesting a similar function in avian species. Furthermore,
      the presence of potentially soluble CD200R molecules implies an important role
      for these in the regulation of myeloid cells in chicken.

PMID- 18062908
TI  - Genetic analysis of complement C1s deficiency associated with systemic lupus
      erythematosus highlights alternative splicing of normal C1s gene.
AB  - Deficiencies of complement proteins of the classical pathway are strongly
      associated with the development of autoimmune diseases. Deficiency of C1r has
      been observed to occur concomitantly with deficiency in C1s and 9 out of 15
      reported cases presented systemic lupus erythematosus (SLE). Here, we describe a
      family in which all four children are deficient in C1s but only two of them
      developed SLE. Hemolytic activity mediated by the alternative and the lectin
      pathways were normal, but classical pathway activation was absent in all
      children's sera. C1s was undetectable, while in the parents' sera it was lower
      than in the normal controls. The levels of C1r observed in the siblings and
      parents sera were lower than in the control, while the concentrations of other
      complement proteins (C3, C4, MBL and MASP-2) were normal in all family members.
      Impairment of C1s synthesis was observed in the patients' fibroblasts when
      analyzed by confocal microscopy. We show that all four siblings are homozygous
      for a mutation at position 938 in exon 6 of the C1s cDNA that creates a premature
      stop codon. Our investigations led us to reveal the presence of previously
      uncharacterized splice variants of C1s mRNA transcripts in normal human cells.
      These variants are derived from the skipping of exon 3 and from the use of an
      alternative 3' splice site within intron 1 which increases the size of exon 2 by
      87 nucleotides.

PMID- 18062909
TI  - Thrombin-induced IL-6 production in human synovial fibroblasts is mediated by
      PAR1, phospholipase C, protein kinase C alpha, c-Src, NF-kappa B and p300
      pathway.
AB  - Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis
      and proinflammatory processes. Abnormalities in these processes are primary
      features of rheumatoid arthritis (RA) in synovial tissues. We investigated the
      signaling pathway involved in IL-6 production caused by thrombin in synovial
      fibroblasts. Thrombin caused concentration- and time-dependent increases in IL-6
      production. By using pharmacological inhibitors or activators or genetic
      inhibition by the protease activated receptor (PAR), siRNA revealed that the PAR1
      receptor but not other PAR receptors is involved in thrombin-mediated up
      regulation of IL-6. Thrombin-mediated IL-6 production was attenuated by thrombin
      inhibitor (PPACK), phospholipase C inhibitor (U73122), protein kinase C alpha
      inhibitor (Ro320432), Src inhibitor (PP2), NF-kappaB inhibitor (PDTC), I kappa B
      protease inhibitor (TPCK), or NF-kappaB inhibitor peptide. Stimulation of
      synovial fibroblasts with thrombin activated I kappa B kinase alpha/beta (IKK
      alpha/beta), I kappa B alpha phosphorylation, I kappa B alpha degradation, p65
      phosphorylation at Ser(276), p65 and p50 translocation from the cytosol to the
      nucleus, and kappaB-luciferase activity. Thrombin-mediated an increase of IKK
      alpha/beta activity, kappaB-luciferase activity and p65 and p50 binding to the NF
      kappaB element was inhibited by PPACK, U73122, Ro320432 and PP2. The binding of
      p65 and p50 to the NF-kappaB elements, as well as the recruitment of p300 and the
      enhancement of p50 acetylation on the IL-6 promoter was enhanced by thrombin. Our
      results suggest that thrombin increased IL-6 production in synovial fibroblasts
      via the PAR1 receptor/PI-PLC/PKC alpha/c-Src/NF-kappaB and p300 signaling
      pathway.

PMID- 18062911
TI  - Applications of dual-color fluorescence cross-correlation spectroscopy in
      antibody binding studies.
AB  - Two-photon dual-color fluorescence cross-correlation spectroscopy (DC-FCCS) was
      applied to study the binding interactions of monoclonal antibodies (mAbs) and
      protein antigens. We measured the binding constant of the interaction of a 32
      amino acid brain natriuretic peptide (BNP) with a mAbs and demonstrated the
      utility of DC-FCCS in studies of antibody sandwiches, trimolecular formations,
      where two different antibodies bind the same antigen simultaneously. We also show
      the use of DC-FCCS for monitoring competitive displacement of the labeled
      antibody in antibody-antigen complexes and subsequent determination of the
      pertinent dissociation rate (off-rate). The off-rate measurements were performed
      for two mAbs toward tissue inhibitor 1 of metalloproteinases (TIMP-1). From a
      methodological perspective, selection of the best labeling protocols and careful
      optimization of the FCCS instrumentation are essential to achieve the highest
      cross-correlation signal. When working in vitro, it is practical to generate a
      complete binding curve using the normalized cross-correlation signal and then fit
      the experimental points to a binding model. DC-FCCS offers the sensitivity and
      all other advantages of a solution phase fluorescence-based technique. For
      systems containing proteins of a similar size that interact without substantial
      changes in the fluorescence intensity, DC-FCCS serves as a preferred means of
      measuring solution phase binding constants.

PMID- 18062910
TI  - MHC class I chain-related molecules induced on monocytes by IFN-gamma promote NK
      cell activation.
AB  - NKG2D receptor-ligand interaction triggers NK cell-mediated cytolysis and IFN
      gamma secretion. IFN-gamma produced by NK cells has been found to promote the
      interaction between NK cells and monocytes; however, the underlying mechanism
      remains elusive. We demonstrate here that IFN-gamma exclusively induced or
      upregulated the expression of MHC class I chain-related (MIC) molecules, which
      are ligands of the NKG2D receptor, on the surface of human monocytes of the PBMC
      population. The IFN-gamma-induced MIC molecules on monocytes played an essential
      role in triggering the activation of NK cells because mAb-mediated masking of the
      MIC molecules and the inhibition of cell-to-cell contact using transwell inserts
      significantly abolished NK cell activation. Meanwhile, membrane-bound IL-15 (mIL
      15) was concomitantly induced with MIC molecules on IFN-gamma-treated monocytes
      and played an essential role in protecting NK cells cocultured with monocytes
      from MIC-induced NKG2D down-modulation. Therefore, we conclude that the IFN-gamma
      induced MIC molecules participated in monocyte/NK cell interaction and that this
      interaction also involved mIL-15.

PMID- 18062912
TI  - Optical fingerprinting of peptides using two-dimensional infrared spectroscopy:
      proof of principle.
AB  - We employ a particular form of two-dimensional infrared four-wave mixing (2DIR
      FWM) as a vibrational spectroscopic tool to quantify the amino acid content of a
      number of peptides. Vibrational features corresponding to ring modes of the
      aromatic groups of phenylalanine (Phe) and tyrosine (Tyr), as well as a methylene
      mode that is used as an internal reference, are identified. We show that the
      ratios of the integrated intensities, and the amplitudes, of the aromatic peaks
      of Phe and Tyr relative to the methylene integrated intensity, and amplitude, are
      proportional to the actual ratio of Phe and Tyr to CH(2) in the samples within a
      precision of +/-12.5%. This precision is shown to be sufficient to use this form
      of 2DIR spectroscopy as a possible proteins fingerprinting tool.

PMID- 18062913
TI  - RNA template-mediated inhibition of hepatitis C virus RNA-dependent RNA
      polymerase activity.
AB  - The enzymatic activity of hepatitis C virus (HCV) RNA-dependent RNA polymerase
      NS5B is modulated by the molar ratio of NS5B enzyme and RNA template. Depending
      on the ratio, either template or enzyme can inhibit activity. Inhibition of NS5B
      activity by RNA template exhibited characteristics of substrate inhibition,
      suggesting the template binds to a secondary site on the enzyme forming an
      inactive complex. Template inhibition was modulated by primer. Increasing
      concentrations of primer restored NS5B activity and decreased the affinity of
      template for the secondary site. Conversely, increasing template concentration
      reduced the affinity of primer binding. The kinetic profiles suggest template
      inhibition results from the binding of template to a site that interferes with
      primer binding and the formation of productive replication complexes.

PMID- 18062914
TI  - Structural insights into the PIP2 recognition by syntenin-1 PDZ domain.
AB  - Lipid-mediated regulatory mechanism of the C-terminal ligand binding to PDZ
      domains is not fully understood, despite their roles in subcellular organization.
      Here, we provide structural insights into the phosphatidylinositol 4,5
      bisphosphate (PIP(2)) recognition mode of a PDZ domain, as revealed from the
      crystal structure of the phosphate-bound PDZ domain. Two adjacent phosphate ions
      bind to the basic residues close to the amino terminus of the alpha2 helix in the
      Tamalin PDZ domain, reflecting an interaction mode of the two phosphate groups of
      PIP(2). Based on the observed location of the two phosphate molecules within the
      PDZ domain, we built the docking model of PIP(2) with the PDZ domain of the well
      known PIP(2)-binding protein, syntenin-1. This model suggests that the
      hydrophobic diacylglycerol group of PIP(2) could contact the ligand-binding
      groove of the PDZ domain. These structural features well explain biological
      phenomena, which were previously reported for the PIP(2)-mediated PDZ ligand
      binding regulation.

PMID- 18062915
TI  - Enrichment of a bipotent hepatic progenitor cell from naive adult liver tissue.
AB  - BACKGROUND/AIM: Recent interest in the liver stem cell field has led to the
      identification and characterization of several hepatic progenitor cell
      populations from fetal and adult tissues. We isolated a hepatic progenitor cell
      from naive adult liver and the current studies focus on differentiation and
      growth. RESULTS: A Sca-1(+) hepatic progenitor cell was identified within the
      liver parenchyma. This cell expresses numerous liver related genes and
      transcription found in the developing and/or adult liver. It is located in the
      peri-portal region and expresses markers associated with undifferentiated hepatic
      cell populations, mature hepatocytes and biliary cells which distinguish it from
      the Sca-1(-) fraction. CONCLUSION: This hepatic progenitor cell from uninjured
      liver has features of both hepatocytic and biliary populations and demonstrates
      proliferative potential. Further studies will focus on sca-HPC subsets and
      conditions that regulate differentiation towards hepatic or biliary lineages.

PMID- 18062916
TI  - Sequential changes in genome-wide DNA methylation status during adipocyte
      differentiation.
AB  - DNA methylation is an epigenetic mark on the mammalian genome. There are numerous
      tissue-dependent and differentially methylated regions (T-DMRs) in the unique
      sequences distributed throughout the genome. To determine the epigenetic changes
      during adipocyte differentiation, we investigated the sequential changes in DNA
      methylation status of 3T3-L1 cells at the growing, confluent, postconfluent and
      mature adipocyte cell stages. Treatment of 3T3-L1 cells with 5-aza-2'
      deoxycytidine inhibited differentiation in a stage-dependent manner, supporting
      the idea that formation of accurate DNA methylation profile, consisting of
      methylated and unmethylated T-DMRs, may be involved in differentiation. Analysis
      by methylation-sensitive quantitative real-time PCR of the 65 known T-DMRs which
      contain NotI sites detected 8 methylations that changed during differentiation,
      and the changes in the patterns of these methylations were diverse, confirming
      that the differentiation process involves epigenetic alteration at the T-DMRs.
      Intriguingly, the dynamics of the methylation change vary depending on the T-DMRs
      and differentiation stages. Restriction landmark genomic scanning detected 32
      novel T-DMRs, demonstrating that differentiation of 3T3-L1 cells involves genome
      wide epigenetic changes by temporal methylation/demethylation, in addition to
      maintenance of a static methylated/demethylated state, and both depend on
      differentiation stage.

PMID- 18062918
TI  - Instability of familial spongiform encephalopathy-related prion mutants.
AB  - We examined the influence of D177N (D178N in humans) mutation on the
      conformational stability of the S2 region of moPrP(C) with varying pHs by using
      the SDSL-ESR technique. The ESR spectrum of D177N at pH 7.5 was narrower than
      that of Y161R1, referred to as WT( *). The ESR spectrum of D177N did not change
      when pH in the solution decreased to pH 4.0. Our results suggested that the
      disappearance of a salt bridge (D177-R163) induced the increase in the
      instability of S2 region. Moreover, the line shape of the ESR spectrum obtained
      from H176S neighboring the salt bridge linked to the S2 region was similar to
      D177N. These results indicate that the protonation of H176 is strongly associated
      with the stability of S2 region. These findings are important for understanding
      the mechanism by which the disruption of the salt bridge in the S2 region forms
      the pathogenic PrP(Sc) structure in hereditary prion disease.

PMID- 18062917
TI  - Twist is a transcriptional repressor of E-cadherin gene expression in breast
      cancer.
AB  - Twist is a basic helix loop helix protein that plays a role both in human
      development and in cancer biogenesis. While characterizing the effects of Twist
      on breast epithelial cell transformation, we identified E-cadherin as a target
      gene that is down-regulated by Twist. In this study, we demonstrate that Twist
      can transcriptionally repress E-cadherin in breast cancer cells. Using transient
      promoter assays, we show that Twist can down-regulate E-cadherin promoter
      activity by up to two folds. This is further supported by immunoblot analyses
      which indicates that over-expression of Twist decreases E-cadherin protein levels
      in breast cancer cell lines. Subsequently, chromatin immunoprecipitation
      performed on MCF-7/Twist and Hs578 T (high level of endogenous Twist expression)
      confirmed Twist binding to the E-cadherin promoter. Finally, the functional
      relevance of this regulation was verified by quantitative real-time PCR and
      immunohistochemistry on a cohort of breast cancer samples.

PMID- 18062919
TI  - Myocardial SSAT induction via AMPK signaling and its implication for ischemic
      injury.
AB  - Spermidine/spermine N-1-acetyl-transferase (SSAT) is a catabolic enzyme that
      participates in polyamine metabolism. SSAT has been reported to be induced in
      some organs subjected to ischemia-reperfusion, but its induction mechanism has
      not been clarified, and little is known about SSAT regulation by ischemia per se.
      We induced regional ischemia of rat heart by coronary ligation and found that
      SSAT expression increased in ischemic myocardium. In neonatal rat cardiomyocytes
      and HEK293 cells, SSAT was up-regulated at the transcriptional step primarily by
      ATP depletion rather than oxygen deprivation. Moreover, an AMPK inhibitor
      compound C and AMPKalpha1-silencing RNAs attenuated the SSAT induction by ATP
      depletion, and an AMPK activator AICAR induced SSAT expression even without ATP
      depletion. When SSAT was suppressed using siRNA, the caspase activities and
      Bax/Bcl-2 ratios further increased in ATP depletion. These results suggest that
      myocardial SSAT is induced by AMPK signaling and function as a cardioprotectant
      under ATP-depleted conditions.

PMID- 18062920
TI  - Ku70 is stabilized by increased cellular SUMO.
AB  - Ku70 is a protein that finds itself at the heart of several important cellular
      processes. It is essential to the non-homologous end joining pathway as a part of
      the DNA-end binding complex, required for proper maintenance of telomeres and
      contributes to DNA damage recognition and regulation of apoptosis. Forces that
      regulate Ku70 are therefore likely to have large consequences on the physiologic
      state of the cell. We report here that transient expression of the small protein
      SUMO resulted in a dramatic increase in the abundance of Ku70. Surprisingly, the
      direct SUMOylation of Ku70 does not appear to be required for this effect.
      Rather, Ku70 appears to be stabilized through indirect effects on the rate of
      degradation. The same outcome was obtained by raising the expression of enzymes
      that promote SUMOylation. It is likely that many other proteins will be similarly
      regulated, providing a general control of cellular state.

PMID- 18062921
TI  - Signaling mechanisms of daidzein-induced axonal outgrowth in hippocampal neurons.
AB  - We aim to study the mechanisms underlying the neurotrophic effect of daidzein
      (Dz) in hippocampal neurons. Dz-enhanced axonal outgrowths manifested growth cone
      formation and increased immunostaining intensity of growth-associated protein 43
      (GAP-43) in growth cones. Consistent with this, Dz increased GAP-43
      phosphorylation and its membrane translocation without affecting total GAP-43
      levels. In the presence of Dz, significant increase in the immunoreactivity for
      estrogen receptor (ER) beta, but not ERalpha, was observed on the membrane of
      cell bodies and growing axons. Dz also induced the activation of protein kinase C
      alpha (PKCalpha), which was inhibited by the ICI182,780 pretreatment. Similarly,
      Dz-promoted axonal elongation was blocked by ICI182,780 and Go6976. Moreover, Dz
      stimulated activation of GAP-43 was specifically abolished by Go6976, suggesting
      PKCalpha being the upstream effector of GAP-43. Taken together, our data suggest
      that Dz triggers an ERbeta/PKCalpha/GAP-43 signaling cascade to promote axonal
      outgrowths in cultured hippocampal neurons.

PMID- 18062922
TI  - Protein folding following synthesis in vitro and in vivo: association of newly
      synthesized protein with 50S subunit of E. coli ribosome.
AB  - In the accompanying paper, it was shown that a protein, while reverting to native
      form from the unfolded state in vitro with the help of bacterial 70S ribosome,
      split the latter into its subunits (50S and 30S) and remains associated with the
      50S subunit. Here, we follow the fate of nascent proteins both in case of in vivo
      and in vitro translation system. The newly synthesised protein was found to
      associate with the 50S subunit in both the cases.

PMID- 18062923
TI  - Performance characteristics of the Architect cortisol immunoassay.

PMID- 18062924
TI  - Competitive and product inhibition-based alpha-amylase activity analysis method.
AB  - OBJECTIVES: To propose a methodology for analyzing salivary alpha-amylase
      activity (sAMY) for a hand-held device that can be used easily and quickly for
      evaluating human psychological effects. METHODS: An improved method for the
      analysis of sAMY is proposed using competitive and product inhibition in a dry
      chemistry system with a reagent paper containing 2-chloro-4-nitrophenyl-4-O-beta
      D-galactopyranosylmaltoside. RESULTS: Not only the competitive (maltopentaose)
      inhibitor, but also the product (maltotriose) inhibitor significantly reduce the
      reaction speed of sAMY. There is an independent effect between the two
      inhibitors. The dynamic linear range of the analysis can be enhanced by 2.5 times
      larger by adding the competitive and product inhibitors simultaneously and by
      preparing their concentrations appropriately. CONCLUSIONS: It is considered that
      the application of competitive and product inhibition can be effective from the
      viewpoint of enhancing analysis range and effectively reducing costs.

PMID- 18062925
TI  - A case-control study of the HER2 Ile655Val polymorphism and risk of breast cancer
      in Taiwan.
AB  - OBJECTIVES: To investigate the HER2 Ile655Val polymorphism in relation to risk of
      breast cancer in a case-control study in Taiwan. DESIGN AND METHODS: The HER2
      polymorphism at codon 655 was analyzed in 424 patients with breast cancer and 318
      controls by using the polymerase chain reaction methodology, followed by the
      restriction fragment-length polymorphism (PCR-RFLP) analysis. RESULTS: There was
      a 1.48-fold (95% CI=1.00-2.24) increase in the risk of patients with breast
      cancer who are Val carrier (Ile/Val and Val/Val genotypes). Furthermore, for the
      early onset (less than 45 years old) breast cancers with Val carrier, there was a
      2.24-fold (95% CI=1.17-4.34) increase in the risk of breast cancer. CONCLUSIONS:
      Our results indicate that the Val carrier was associated with increased risks in
      patients with breast cancer in Taiwan. The association was more apparent in
      patients who were younger than or equal to 45 years of age.

PMID- 18062926
TI  - Identification of a novel human MT5-MMP transcript variant in multipotent NT2
      cells.
AB  - Membrane-type 5 matrix metalloproteinase (MT5-MMP) expression is ubiquitous in
      brain development while restricted to regions of neuroplasticity in adult. In the
      multipotent NT2 model of neurogenesis and differentiation, MT5-MMP is
      differentially expressed with significantly higher mRNA levels in the
      differentiated neuronal hNT cells. MT5-MMP cDNA cloned from NT2 cells
      unexpectedly revealed a novel sequence (MT5-MMPvar) characterized by a 162bp
      deletion. Both transcripts were identified in NT2, hNT and adult human
      hippocampus. In vitro, MT5-MMPvar translated into a approximately 55 kDa protein.
      It was also detected in NT2, hNT and adult human hippocampus. These results
      suggest more than one human MT5-MMP transcript may exist in the central nervous
      system.

PMID- 18062927
TI  - VDUP1 mediates nuclear export of HIF1alpha via CRM1-dependent pathway.
AB  - Hypoxia-inducible factor 1alpha (HIF1alpha) is a critical transcriptional factor
      for inducing tumor metastasis, and stabilized under hypoxia but degraded by von
      Hippel-Lindau protein (pVHL) under normoxia. For the maximal degradation of
      HIF1alpha, it must be exported to the cytoplasm via an unidentified transporter.
      Here, we demonstrate that vitamin D3 up-regulated protein 1 (VDUP1) associates
      with the beta-domain of pVHL and enhances the interaction between pVHL and
      HIF1alpha to promote the nuclear export and degradation of HIF1alpha hypoxia
      independently. Blocking of VDUP1 translocation either by leptomycin B or by
      nuclear export signal mutation inhibited the nuclear export of pVHL/HIF1alpha and
      relieved the destabilization of HIF1alpha. VDUP1 suppressed cell invasiveness and
      tumor metastasis, which were also recovered by blocking of nuclear export. Taken
      together, these findings indicate that VDUP1 is a novel tumor suppressor which
      mediates the nuclear export of pVHL/HIF1alpha complex to destabilize HIF1alpha.

PMID- 18062928
TI  - Modulation by insulin-like growth factor I of the phosphatase PTEN in astrocytes.
AB  - Characterization of intracellular pathways underlying the pleiotropic actions of
      insulin-like growth factor-I (IGF-I) on brain cells is incomplete. We analyzed
      IGF-I signalling on astrocytes through the canonical phosphatidylinositol 3
      kinase (PI3K)/Akt pathway and focused on possible changes in PTEN, a phosphatase
      that modulates IGF-I signalling by inhibiting Akt activation and, in turn is
      positively regulated by PI3K. After exposure of astrocytes to IGF-I, PTEN mRNA
      and protein levels were reduced and its phosphatase activity diminished.
      Inhibition of PTEN involved activation of a PI3K/protein kinase C (PKC) pathway
      that decreased in a proteasome-dependent step the levels of the transcription
      factor Egr-1, a key regulator of PTEN levels in astrocytes, causing decreased
      binding of Egr-1 to the PTEN promoter. Enhanced mitogenesis in PTEN siRNA
      transduced astrocytes after IGF-I suggested that reduced PTEN may be a permissive
      factor for the mitogenic activity of IGF-I. Subsequent recovery of reduced PTEN
      required also activation by IGF-I of PI3K to recruit in this case protein kinase
      A (PKA) which stimulated Egr-1 levels and, consequently PTEN synthesis. Because
      basal levels of PTEN in astrocytes are also governed by PI3K, IGF-I appears to
      modulate PTEN in astrocytes by redirecting its homeostasic control through PI3K
      in a timed fashion.

PMID- 18062929
TI  - Nuclear receptors and other nuclear transcription factors in mitochondria:
      regulatory molecules in a new environment.
AB  - The mitochondrion is the major energy generating organelle of the cell and the
      site of other basic processes, including apoptosis. The mitochondrial functions
      are performed in concert with other cell compartments and are regulated by
      various extracellular and intracellular signals. Several nuclear receptors and
      other nuclear transcription factors, such as NF-kappa B, AP-1, CREB and p53,
      involved in growth, metabolic and developmental processes, have been detected in
      mitochondria. This finding raises the question as to the role of these regulatory
      molecules in their "new" environment. Experimental evidence supports the action
      of the mitochondrially localized transcription factors on mitochondrial
      transcription, energy yield and apoptosis, extending the known nuclear role of
      these molecules outside the nucleus. A principle of coordination of nuclear and
      mitochondrial gene transcription has been ascertained as regards the regulatory
      action of steroid and thyroid hormones on energy yield. Accordingly, the same
      nuclear receptors, localized in the two compartments-nuclei and mitochondria
      regulate transcription of genes serving a common function by way of interaction
      with common binding sites in the two genomes. This principle is now expanding to
      encompass other nuclearly and mitochondrially localized transcription factors.

PMID- 18062930
TI  - Functional characterisation of the Schizosaccharomyces pombe homologue of the
      leukaemia-associated translocation breakpoint binding protein translin and its
      binding partner, TRAX.
AB  - Translin is a conserved protein which associates with the breakpoint junctions of
      chromosomal translocations linked with the development of some human cancers. It
      binds to both DNA and RNA and has been implicated in mRNA metabolism and
      regulation of genome stability. It has a binding partner, translin-associated
      protein X (TRAX), levels of which are regulated by the translin protein in higher
      eukaryotes. In this study we find that this regulatory function is conserved in
      the lower eukaryotes, suggesting that translin and TRAX have important functions
      which provide a selective advantage to both unicellular and multi-cellular
      eukaryotes, indicating that this function may not be tissue-specific in nature.
      However, to date, the biological importance of translin and TRAX remains unclear.
      Here we systematically investigate proposals that suggest translin and TRAX play
      roles in controlling mitotic cell proliferation, DNA damage responses, genome
      stability, meiotic/mitotic recombination and stability of GT-rich repeat
      sequences. We find no evidence for translin and/or TRAX primary function in these
      pathways, indicating that the conserved biochemical function of translin is not
      implicated in primary pathways for regulating genome stability and/or
      segregation.

PMID- 18062932
TI  - Avenanthramides, polyphenols from oats, inhibit IL-1beta-induced NF-kappaB
      activation in endothelial cells.
AB  - The chronic inflammation of arterial walls is associated with the development of
      atherosclerosis. Earlier we reported that avenanthramide (Avn)s-enriched extract
      of oats (AvnsO) significantly suppressed interleukin (IL)-1beta-stimulated
      secretion of proinflammatory cytokines, such as IL-6, IL-8, and MCP-1, by human
      aortic endothelial cells (HAEC). The main objective of the current study was to
      determine if the mechanism of inhibitory effect of these polyphenols from oats on
      the expression of proinflammatory cytokines is mediated through modulation of
      nuclear factor kappaB (NF-kappaB)-dependent transcription. Confluent HAEC
      monolayers were treated for 24 h with AvnsO, and synthetically prepared Avn-c
      suppressed IL-beta-stimulated activation of NF-kappaB in a concentration
      dependent manner. CH3-Avn-c, a synthetically prepared methyl ester derivative of
      Avn-c with a high biological potency, significantly and dose dependently
      decreased mRNA expression and secretion of IL-6, IL-8, and MCP-1 by HAEC as
      determined by real-time RT-PCR and ELISA, and it inhibited IL-1beta- and TNFalpha
      stimulated NF-kappaB activation as determined by a NF-kappaB DNA binding assay
      and a NF-kappaB luciferase reporter assay. AvnsO and Avn-c as well as CH3-Avn-c
      also inhibited the NF-kappaB-dependent reporter gene expression activated by TNFR
      associated factor 2 and 6 (TRAF2, TRAF6) and NFkappaB-inducing kinase (NIK). CH3
      Avn-c also significantly and dose dependently decreased the phosphorylation level
      of IkappaB kinase (IKK) and IkappaB, and prevented IkappaB degradation as
      measured by Western blotting. In addition, CH3-Avn-c markedly increased the
      overall levels of high mass ubiquitin-conjugated protein levels while it mildly
      inhibited proteasome activity. These observations suggest that Avns, unique
      polyphenols from oats, decrease the expression of endothelial proinflammatory
      cytokines at least in part through inhibition of NF-kappaB activation by
      inhibiting the phosphorylation of IKK and IkappaB, and by suppressing proteasome
      activity.

PMID- 18062931
TI  - Keap1 modification and nuclear accumulation in response to S-nitrosocysteine.
AB  - Keap1 is a key regulator of the Nrf2 transcription factor, which transactivates
      the antioxidant response element (ARE) and upregulates numerous proteins involved
      in antioxidant defense. Under basal conditions, Keap1 targets Nrf2 for
      ubiquitination and proteolytic degradation and as such is responsible for the
      rapid turnover of Nrf2. In response to oxidants and electrophiles, Nrf2 is
      stabilized and accumulates in the nucleus. The mechanism for this effect has been
      proposed to involve thiol-dependent modulation of Keap1 leading to loss of its
      ability to negatively regulate Nrf2. We have previously shown that nitric oxide
      and S-nitrosothiols cause nuclear accumulation of Nrf2 and upregulation of the
      ARE-regulated gene HO-1. Here we show that nitric oxide and S-nitrosocysteine
      (CSNO) cause time- and dose-dependent Keap1 thiol modification. These studies
      were carried out in HEK293 cells and in HEK293 cells overexpressing hemagglutinin
      tagged Keap1. Furthermore we demonstrate that in response to CSNO Keap1
      accumulates in the nucleus with a time course similar to that of Nrf2.

PMID- 18062933
TI  - Tenascin C interacts with ecto-5'-nucleotidase (eN) and regulates adenosine
      generation in cancer cells.
AB  - Tenascin C is expressed in invasive human solid tumors; however its specific role
      in cancer biology remains obscure. Previously, we have found that ecto-5'
      nucleotidase (eN) is a marker of ER (-) breast carcinoma and elevated expression
      correlates with invasive mesenchymal cell phenotype. To investigate for the
      potential relationship between eN and protein components of the extracellular
      matrix (ECM) we measured adenosine generation from AMP in cells incubated with
      soluble ECM proteins. We found that tenascin C was the only ECM component that
      strongly inhibited ecto-5'-nucleotidase (eN) activity in situ and adenosine
      generation from AMP (75% inhibition, p < 0.01). The inhibition was comparable to
      that induced by concanavalin A, a well-defined and strong inhibitor of eN. Resin
      immobilized tenascin C, but not collagen, and only weakly fibronectin,
      specifically and quantitatively bound cell-extracted eN. We further developed
      breast cancer cell line with reduced eN expression and tested changes in cell
      adhesion on different ECM. Breast cancer cells expressing reduced eN attached 56%
      weaker (p < 0.05) to immobilized tenascin C. This difference was not detected
      with other ECM proteins. Finally, control breast cancer cells migrated slower on
      tenascin C when compared with clone with reduced eN expression. These data
      suggest that eN is a novel and specific receptor for tenascin C and that the
      interaction between these proteins may influence cell adhesion and migration and
      also lead to decreased generation of local adenosine.

PMID- 18062934
TI  - X-ray crystal structure of Mycobacterium tuberculosis haloalkane dehalogenase
      Rv2579.
AB  - Haloalkane dehalogenases are enzymes well known to be important in
      bioremediation; the organisms from which they are produced are able to clean up
      toxic organohalides from polluted environments. However, besides being found in
      such contaminated environments, these enzymes have also been found in root or
      tissue-colonizing bacterial species. The haloalkane dehalogenase Rv2579 from
      Mycobacterium tuberculosis H37Rv has been cloned, expressed, purified and its
      crystal structure determined at high resolution (1.2A). In addition, the crystal
      structure of the enzyme has been determined in complex with the product from the
      reaction with 1,3-dibromopropane, i.e. 1,3-propanediol and in complex with the
      classical substrate of haloalkane dehalogenases, 1,2-dichloroethane. The enzyme
      is a two-domain protein having a catalytic domain of an alpha/beta hydrolase fold
      and a cap domain. The active site residues and the halide-stabilizing residues
      have been identified as Asp109, Glu133, His273, Asn39 and Trp110. Its overall
      structure is similar to those of other known haloalkane dehalogenases. Its
      mechanism of action involves an SN2 nucleophilic displacement.

PMID- 18062935
TI  - Transscleral fine-needle aspiration biopsy of macular choroidal melanoma.
AB  - PURPOSE: To report transscleral 30-gauge fine-needle aspiration biopsy (FNAB) for
      cytology and cytogenetics in eyes with macular choroidal melanoma. DESIGN:
      Prospective, interventional case series. METHODS: Twenty-five patients (25 eyes)
      who underwent transscleral 30-gauge FNAB of macular choroidal melanoma
      immediately prior to iodine-125 plaque placement were included in this study,
      conducted at a tertiary care university hospital. The main outcome measures were
      FNAB feasibility, cytology, cytogenetic analysis for monosomy 3, and surgical
      complications. RESULTS: Transscleral 30-gauge FNAB of choroidal melanoma in the
      macula was performed in 24 of 25 (96%) eyes and was not feasible owing to
      insufficient exposure in one eye (4%). Biopsy was diagnostic of choroidal
      melanoma in 17 of 24 (71%) eyes. Fluorescent in situ hybridization (FISH) and/or
      GeneChip 500k NspI Mapping array (Affymetrix, Santa Clara, California, USA)
      analysis for monosomy 3 was completed in 16 of 24 (67%) revealing monosomy 3 in
      five eyes and disomy 3 in 11 eyes. Retinal perforation (four eyes) did not
      require treatment or result in retinal detachment; submacular hemorrhage (nine
      eyes) and vitreous hemorrhage (five eyes) cleared spontaneously within one month.
      CONCLUSION: Transscleral FNAB of macular choroidal melanoma is feasible in most
      eyes and frequently yields cytogenetic information relevant to prognosis.

PMID- 18062936
TI  - Assessment of heart failure and left ventricular systolic dysfunction after
      cardiac pacing in patients with preserved left ventricular systolic function.
AB  - BACKGROUND: There is an accumulating data suggesting the deleterious effects of
      right ventricular pacing on left ventricular performance. Such pacing mimics left
      bundle branch block resulting in a prolonged QRS duration and causes ventricular
      asynchrony. AIMS: The purpose of this study is to assess heart failure and left
      ventricular systolic function after cardiac pacemaker implantation in patients
      with atrioventricular block and preserved systolic left ventricular function.
      Secondly, we sought to search for predictive factors of developing left
      ventricular dysfunction after pacing. METHODS: In this prospective study, we
      included patients who had been implanted for at least six months. They underwent
      medical history and examination, 12 leads electrocardiogram and echocardiography
      before pacemaker implantation and when attending to routine pacemaker follow up.
      RESULTS: Forty-three patients (22 men and 21 women, age 71+/-12 years) were
      included in this study. Twenty-nine patients had DDD pacing and 14 VVI pacing.
      The ventricular lead was implanted in the apex in all patients. After a median
      follow up of 18+/-11 months, 11 patients (25%) developed signs of congestive
      heart failure. NYHA was higher after implantation (1.64+/-0.7 versus 2.27+/-0.8,
      p>0.00001). Left ventricular ejection fraction decreased significantly during
      follow up (60+/-6% versus 51+/-13%, p=0.0002). Eleven (25%) patients developed
      left ventricular dysfunction. We compared patients who had left ventricular
      ejection fraction (LV EF) less or equal to 40% (group A) and patients having LV
      EF greater than 40% (group B) after implantation. Patients in group A had a paced
      QRS width significantly larger than group B (181+/-32 ms versus 151+/-26 ms,
      p=0.002), a significantly prolonged intra left ventricular electromechanical
      delay (115+/-59 ms versus 45+/-35 ms, p<0.0001) and interventricular delay (44+/
      29 ms versus 27+/-18 ms, p=0.02). Age, sex, diabetes hypertension, pacing mode
      and percentage of ventricular pacing were similar in both groups. A paced QRS
      width of 180 ms had the best sensitivity and specificity for detecting left
      ventricular dysfunction: sensitivity=54% and specificity=93%, p=0.01, area under
      the curve=0.75. CONCLUSION: Patients with atrioventricular block and preserved
      left ventricular systolic function at baseline decrease significantly left
      ventricular ejection fraction after pacing. Induced ventricular asynchronism
      plays a major role in the deterioration of left ventricular function. Prolonged
      paced QRS width is a good predictor of left ventricular dysfunction after pacing.
      Larger prospective studies are needed to confirm these data.

PMID- 18062937
TI  - Proteasomal inhibition stabilizes topoisomerase IIalpha protein and reverses
      resistance to the topoisomerase II poison ethonafide (AMP-53, 6-ethoxyazonafide).
AB  - Multiple myeloma (MM) is an incurable malignancy of plasma cells. Although
      multiple myeloma patients often respond to initial therapy, the majority of
      patients will relapse with disease that is refractory to further drug treatment.
      Thus, new therapeutic strategies are needed. One common mechanism of acquired
      drug resistance involves a reduction in the expression or function of the drug
      target. We hypothesized that the cytotoxic activity of topoisomerase II (topo II)
      poisons could be enhanced, and drug resistance overcome, by increasing the
      expression and activity of the drug target, topo II in myeloma cells. To test
      this hypothesis, we evaluated the cytotoxicity of the anthracene-containing topo
      II poison, ethonafide (AMP-53/6-ethoxyazonafide), in combination with the
      proteasome inhibitor bortezomib (PS-341/Velcade). Combination drug activity
      studies were done in 8226/S myeloma cells and its drug resistant subclone,
      8226/Dox1V. We found that a 24-h treatment of cells with bortezomib maximally
      increased topo IIalpha protein expression and activity, and consistently
      increased the cytotoxicity of ethonafide in the 8226/S and 8226/Dox1V cell lines.
      This increase in cytotoxicity corresponded to an increase in DNA double-strand
      breaks, as measured by the neutral comet assay. Therefore, increasing topo
      IIalpha expression through inhibition of proteasomal degradation increased DNA
      double-strand breaks and enhanced the cytotoxicity of the topo II poison
      ethonafide. These data suggest that bortezomib-mediated stabilization of topo
      IIalpha expression may potentiate the cytotoxic activity of topo II poisons and
      thereby, provide a strategy to circumvent drug resistance.

PMID- 18062938
TI  - mRNA expression of activity-regulated cytoskeleton-associated protein (arc) in
      the amygdala-kindled rats.
AB  - Activity-regulated cytoskeleton-associated protein (arc) is an immediate early
      gene (IEG) whose mRNA is targeted to dendrites of activated synapses. The present
      study investigated the expression of three IEGs, arc and two transcription
      factors (NGFI-B and Nurr 1), in regions of the brain of rats that were subjected
      to a single afterdischarge-inducing electrical stimulation of the left amygdala
      and in the amygdala-kindled rats that developed consecutive generalized seizures.
      One hour after a single stimulus was administered to non-kindled rats, mRNA
      levels of arc and Nurr1 increased significantly in the ipsilateral piriform
      cortex and medial amygdaloid nucleus. mRNA levels of NGFI-B increased
      significantly in the left piriform cortex, basolateral amygdaloid nucleus and
      medial amygdaloid nucleus. In the amygdala-kindled rats, mRNAs of the three IEGs
      increased significantly in bilateral brain regions including the piriform cortex
      and dentate gyrus at 0.5-1 h after the last generalized kindled seizure, and
      returned near to basal levels by 6 h after. Photographic emulsion autoradiograms
      showed that the arc mRNA signals induced by the last generalized kindled seizures
      were associated with the cell bodies of the dentate granule cell layer and
      extended beyond the granule cell layer into the molecular layer, which contains
      the dendrites of granule cells. These results support that arc serves as an
      effector IEG whose mRNA is associated with synaptic reorganization in kindling.

PMID- 18062939
TI  - Activation patterns in visual cortex reveal receptive field size-dependent
      attentional modulation.
AB  - Because our brain cannot process all visual information that enters it, we
      usually pay attention to only a specific aspect of our visual world. Selective
      visual attention modulates brain activation in cortical areas corresponding to
      the attended spatial location. However, visual attention has also been associated
      with the modulation of activation in different brain areas depending on the
      relevant spatial scale. In this study, we establish a link between attended
      spatial scale and receptive field size. We demonstrate that attention to a large
      or a small object in a visual scene increases activation specifically in brain
      regions with correspondingly large or small receptive field sizes. To analyze and
      visualize differential brain activation in contiguous cortical areas we used a
      mapping strategy evaluating the modelling parameters (beta) from functional
      magnetic resonance imaging data analysis. Assessment of the course of these
      parameters along traces in different directions in the visual cortex strengthens
      our conclusion that selective visual attention modulates brain areas with
      specific neuronal receptive field size properties corresponding to the task at
      hand. This also confirms predictions of models of selective attention, that
      attentional modulation of visual processing critically depends on the receptive
      field size of neurons across the visual cortex.

PMID- 18062941
TI  - McGurk effects in cochlear-implanted deaf subjects.
AB  - Cochlear implants are neuroprostheses designed to restore speech perception in
      case of profound bilateral hearing loss. As speech is fundamentally an
      audiovisual percept, a deficit in processing auditory information might lead to
      changes in audiovisual integration of speech comprehension. Using vowel-consonant
      vowel stimuli under unimodal, audiovisual congruent and audiovisual incongruent
      (McGurk) conditions, we tested postlingually deaf cochlear-implanted (CI) users
      and normally hearing (NH) subjects in order to investigate their audiovisual
      perceptive strategies. Mode/Place-of-articulation perceptive analysis and
      information transmission analysis of congruent and incongruent percepts indicated
      a similar sensory specialization for CI users when compared to NH subjects, with
      voicing and nasality cues transmitted via audition and place cues principally
      transmitted via vision. NH as well as CI subjects underwent typical McGurk
      illusory percepts. However, while normally hearing subjects show a well-balanced
      bimodal integration of incongruent speech, we demonstrated that cochlear
      implantees present a bias toward a visual-predominant bimodal integration. Our
      results are complementary to previous studies showing that CI users maintain a
      high level of speechreading, even after several years of recovery of auditory
      speech comprehension. Altogether, our results suggest a cross-modal
      reorganization of speech comprehension in cochlear-implanted patients that might
      recruit more strongly than in NH the visual and visuo-auditory brain areas
      involved in speechreading.

PMID- 18062940
TI  - On-line activation of orthography in spoken word recognition.
AB  - An increasing number of studies suggest that learning to read changes the way the
      brain processes spoken language. Yet, there is still a hot debate about the locus
      of these literacy effects. While most psycholinguists would argue that these
      effects are late and postlexical, interactive theories of word recognition
      suggest that orthography might affect the core processes of spoken word
      recognition (lexical access). Event-related brain potentials (ERPs) were used to
      track the on-line activation of orthography in spoken word recognition. We
      manipulated the orthographic consistency of spoken words at two positions: early
      or late. The results showed prelexical and lexical ERP differences between
      orthographically consistent and inconsistent words. Most importantly, the ERP
      differences were time-locked to the "arrival" of the orthographic inconsistency,
      which provides the strongest evidence available thus far in favor of on-line
      activation of orthography during spoken word recognition.

PMID- 18062942
TI  - Nitric oxide/cGMP pathway mediates orofacial antinociception induced by
      electroacupuncture at the St36 acupoint.
AB  - The aim of the present study was to test the hypothesis that electroacupuncture
      (EA) at acupoint St36 induces antinociception by activation of the L-arg/NO/cGMP
      pathway. Nociception was produced by thermal stimuli applied to the face of
      Wistar rats and latency was measured by face withdrawal. Electric stimulation of
      acupoint St36 for 20 min induced antinociception in this model, which was
      maintained for 150 min. For comparison, a so-called dry needle group (DN) was
      used, which received needling at the same point without stimulation. The
      antinociception obtained by stimulation of acupoint St36 was only achieved when
      high frequency (100 Hz) was used, whereas low frequencies (5 and 30 Hz) were not
      capable of achieving this effect. Subcutaneous administration of both inhibitors
      of NO synthase (N-nitro-L-arginine) and guanylyl cyclase (ODQ) and
      intraperitoneal administration of specific antagonists of neuronal NO synthase (L
      NNA) and inductible NO synthase (aminoguanidine) antagonized the antinociception
      induced by St36 stimulation. The results of this paper suggest that stimulation
      of acupoint St36 at high frequency induces antinociception, which seems to be
      related to L-arg/NO/cGMP pathway activation.

PMID- 18062943
TI  - Further studies in the developmental hyperserotonemia model (DHS) of autism:
      social, behavioral and peptide changes.
AB  - Prior research has reliably found high blood (hyperserotonemia) - but low brain -
      serotonin levels in autistic individuals. At early stages of development, high
      levels of serotonin in the blood may enter the brain of a developing fetus,
      causing a loss of serotonin terminals through negative feedback and thus
      disrupting subsequent serotonergic function. The current study extends earlier
      findings in a developmental hyperserotonemia (DHS) model of autism in Sprague
      Dawley rats by treating 8 dams of developing rat pups with a serotonergic
      agonist, 5-methoxytryptamine (5-MT; 1 mg/kg) during development (from gestational
      day 12 to post-natal day 20; PND 20). DHS pups exhibited post-injection seizures,
      which were non-existent in saline-treated pups (p<0.05). Behavioral results in
      infancy indicated that DHS pups spent less time with the dam during the active
      phase on PNDs 15-17 (p<0.05) and experienced decreased maternal bonding in a
      return to dam task on PND 17 (p<0.05). On subsequent tests, DHS animals exhibited
      greater gnawing reactions to a novel stimulus (p<0.05), less behavioral
      inhibition (p<0.05), and had fewer olfactory-based social interactions (p<0.05)
      and greater non-olfactory mounting (p<0.05). However, there were no changes in
      anxiogenic behavior using the elevated plus maze (p>0.05). Post mortem analyses
      revealed that DHS animals had a loss of oxytocin (OT)-containing cells in the
      paraventricular nucleus in the hypothalamus (PVN; p<0.05) as well as an increase
      in calcitonin-gene related peptide (CGRP; p<0.05, one tailed) processes in the
      central nucleus of the amygdala (CeA) on PND 198. These results may correspond to
      hypothalamic and amygdalar changes in the human condition and suggest that the
      hyperserotonemia model of autism may be a valid model which produces many of the
      social, behavioral, and peptide changes inherent to autism.

PMID- 18062944
TI  - Atrophy and degeneration in sciatic nerve of presymptomatic mice carrying the
      Huntington's disease mutation.
AB  - Huntington's disease (HD) is a progressive neurological disorder characterised by
      motor impairments caused by degeneration in the striatum. The mechanism by which
      the HD mutation leads to the neurodegenerative pathology of HD is still unknown.
      Recently it was shown that, in HD patients, early pathological changes in white
      matter precede selective cell death in the striatum. We wondered whether axonal
      pathology is also an early pathological feature in a transgenic mouse model
      carrying the HD mutation (R/2 line). R6/2 mice show brain atrophy, a progressive
      neurological deterioration and skeletal muscle atrophy that resemble those seen
      in HD patients. However, there is very little neuronal cell loss seen in these
      animals, even when they show severe symptoms. Here we used sciatic nerve to look
      for evidence of early neurodegenerative changes in axons of the R6/2 mouse at an
      ultrastructural level. We observed ultrastructural changes that preferentially
      affected large myelinated fibres of the sciatic nerve in 10-week-old asymptomatic
      R6/2 mice. The changes included a significant decrease in the axoplasm diameter
      of myelinated neurons and an increase in the number of degenerating myelinated
      fibres compared to age-matched wild type littermates. Myelin thickness and
      unmyelinated fibre diameter were not affected. The abnormalities described here
      precede the appearance of overt motor symptoms in the R6/2 mouse and occur in
      parallel with pathophysiological changes at the neuromuscular junction. We
      suggest that degenerative changes in axons are likely to contribute to the early
      pathological phenotype in HD, even in the absence of frank neuronal cell loss.

PMID- 18062945
TI  - Unexpected formation of complex bridged tetrazoles via intramolecular 1,3-dipolar
      cycloaddition of 1,2-O-cyanoalkylidene derivatives of 3-azido-3-deoxy-D-allose.
AB  - An unexpected and interesting intramolecular side reaction occurred during the
      attempted synthesis of glycosyl cyanides upon treatment of 1-O-acetyl-3-azido-3
      deoxyallose derivatives with TMSCN and different Lewis acids. Exo-1,2-O
      cyanoalkylidene derivatives formed by neighboring group participation and attack
      of cyanide underwent, after Lewis-acid mediated isomerization to the endo-isomer,
      intramolecular azide-cyanide cycloaddition leading to the formation of tetrazoles
      embedded in bridged tetracyclic ring systems. The efficiency of cycloaddition is
      dependent on the ring structure of the sugar (pyranose or furanose). Of the
      studied molecules, 3-azido-1,2-O-cyanoethylidene-3-deoxy-allopyranose provides
      the most suitable scaffold for intramolecular [2+3] cycloaddition under
      exceptionally mild conditions. Our results highlight the capability of
      carbohydrates to act as scaffolds for the precise positioning of functional
      groups productive for a specific chemical reaction.

PMID- 18062946
TI  - Structure of the O-polysaccharide of Escherichia coli O112ab containing L
      iduronic acid.
AB  - An acidic O-polysaccharide was isolated by mild acid degradation of the
      lipopolysaccharide of Escherichia coli O112ab and studied by sugar analysis along
      with (1)H and (13)C NMR spectroscopy. The O-polysaccharide was found to contain a
      rarely occurring sugar component, L-iduronic acid (L-IdoA), and the following
      structure of the branched pentasaccharide repeating unit was established:
      [structure: see text].

PMID- 18062947
TI  - An alternative approach for the synthesis of fluorogenic substrates of endo-beta
      (1-->4)-xylanases and some applications.
AB  - Fluorogenic substrates of endo-beta-(1-->4)-xylanases (EXs), 4-methylumbelliferyl
      beta-glycosides of xylobiose and xylotriose were synthesized from fully
      acetylated oligosaccharides using the alpha-trichloroacetimidate procedure. A
      commercially available syrup containing xylose and xylo-oligosaccharides was used
      as the starting material. Both fluorogenic glycosides were found to be suitable
      substrates for EXs, particularly for sensitive detection of the enzymes in
      electrophoretic gels and their in situ localization on sections of fruiting
      bodies of some plants, such as tomato, potato and eggplant, all of the family
      Solanaceae.

PMID- 18062948
TI  - Reorientation in the real world: the development of landmark use and integration
      in a natural environment.
AB  - An influential series of studies have argued that young children are unable to
      use landmark information to reorient. However, these studies have used artificial
      experimental environments that may lead to an underestimation of the children's
      ability. We tested whether young children could reorient using landmarks in an
      ecologically valid setting. Children aged between 3 and 7 years completed a
      reorientation task in open parkland, and the properties of the search array (size
      and distinctiveness) were manipulated in a within-subjects design. Responses were
      recorded using Global Positioning Systems technology. All age groups performed
      above chance level, demonstrating that young children can reorient using natural
      landmarks. This behaviour was modulated by the nature of the search array:
      children were more accurate when the locations were spaced in a large array, and
      when the search locations were distinctively coloured. This suggests that the
      integration between landmarks and search locations, at different spatial scales,
      is a key factor in characterising human reorientation in the real world.

PMID- 18062949
TI  - Validating an imaging and analysis system for assessing torso deformities.
AB  - We present the results of the numeric and functional validation of an imaging and
      analysis system used for assessing human torsos for deformities such as
      scoliosis. The system comprises of image acquisition, image reconstruction, and
      shape analysis components. The numeric validation procedure consists of assessing
      the accuracy of reconstruction of the system using inanimate models (a
      calibration box and a mannequin). The functional validation involves determining
      the system's response to variations in shape caused by sway and breathing, and
      evaluating the variability of a clinically relevant index, the Cosmetic Score,
      from multiple scans of scoliosis and non-scoliosis volunteers. Results show that
      the reconstruction accuracy of the system is 1.16+/-1.04 mm. This is better than
      the required accuracy for monitoring scoliosis of 2 mm. The system is robust to
      shape variations caused by sway and breathing and shows limited variability to
      the Cosmetic Score.

PMID- 18062950
TI  - Heterogeneity in imprinted methylation patterns of pluripotent embryonic germ
      cells derived from pre-migratory mouse germ cells.
AB  - Pluripotent stem cells, termed embryonic germ (EG) cells, have been generated
      from both human and mouse primordial germ cells (PGCs). Like embryonic stem (ES)
      cells, EG cells have the potential to differentiate into all germ layer
      derivatives and may also be important for any future clinical applications. The
      development of PGCs in vivo is accompanied by major epigenetic changes including
      DNA demethylation and imprint erasure. We have investigated the DNA methylation
      pattern of several imprinted genes and repetitive elements in mouse EG cell lines
      before and after differentiation. Analysed cell lines were derived soon after PGC
      specification, "early", in comparison with EG cells derived after PGC
      colonisation of the genital ridge, "late" and embryonic stem (ES) cell lines,
      derived from the inner cell mass (ICM). Early EG cell lines showed strikingly
      heterogeneous DNA methylation patterns, in contrast to the uniformity of
      methylation pattern seen in somatic cells (control), late EG cell and ES cell
      lines. We also observed that all analysed XX cell lines exhibited less
      methylation than XY. We suggest that this heterogeneity may reflect the changes
      in DNA methylation taking place in the germ cell lineage soon after
      specification.

PMID- 18062951
TI  - Overexpression of pairedless Pax6 in the retina disrupts corneal development and
      affects lens cell survival.
AB  - The Pax6 transcription factor is required for multiple aspects of vertebrate eye
      development. The Pax6 gene encodes isoforms that either contain (Pax6+PD) or lack
      (Pax6DeltaPD) the N-terminal paired-box DNA-binding domain, in addition to the
      homeodomain. Alternative promoters control the expression of Pax6+PD and
      Pax6DeltaPD in the eye. Using a modified bacterial artificial chromosome (BAC)
      transgene that specifically expresses Pax6DeltaPD, but not paired-containing
      Pax6, in the normal endogenous pattern, we show that overexpression of
      Pax6DeltaPD causes a severe microphthalmic phenotype in both wild-type and Pax6
      deficient (Sey(/+)) mice in a dosage-dependent manner. The microphthalmic
      phenotype is due to lens degeneration during embryonic development. Lens
      development initiates correctly, but cells in the lens undergo apoptotic cell
      death between E12 and E13. Concomitantly, in these mice, changes in Bmp4, Msx1,
      and Wnt2b expression were observed in the mesenchymal cells of the developing
      cornea. To visualize Pax6DeltaPD expression, we developed a dual-reporter Pax6
      BAC transgene in which EGFP and DsRed demonstrate paired-containing and
      pairedless transcripts, respectively. In BAC transgenic mice, DsRed is
      predominantly expressed in the peripheral neural retina during early eye
      development, but not in the developing lens or cornea. Later DsRed is strongly
      expressed in the developing ciliary body, but not in the iris. We suggest that
      the ratio of Pax6+PD and Pax6DeltaPD isoforms in the distal retina is important
      for both cornea and lens development, either directly by controlling
      transcription of necessary growth factors or indirectly by controlling
      development of the distal neural retina.

PMID- 18062952
TI  - Efficient chaperone-mediated tubulin biogenesis is essential for cell division
      and cell migration in C. elegans.
AB  - The efficient folding of actin and tubulin in vitro and in Saccharomyces
      cerevisiae is known to require the molecular chaperones prefoldin and CCT, yet
      little is known about the functions of these chaperones in multicellular
      organisms. Whereas none of the six prefoldin genes are essential in yeast, where
      prefoldin-independent folding of actin and tubulin is sufficient for viability,
      we demonstrate that reducing prefoldin function by RNAi in Caenorhabditis elegans
      causes defects in cell division that result in embryonic lethality. Our analyses
      suggest that these defects result mainly from a decrease in alpha-tubulin levels
      and a subsequent reduction in the microtubule growth rate. Prefoldin subunit 1
      (pfd-1) mutant animals with maternally contributed PFD-1 develop to the L4 larval
      stage with gonadogenesis defects that include aberrant distal tip cell migration.
      Importantly, RNAi knockdown of prefoldin, CCT or tubulin in developing animals
      phenocopy the pfd-1 cell migration phenotype. Furthermore, reducing CCT function
      causes more severe phenotypes (compared with prefoldin knockdown) in the embryo
      and developing gonad, consistent with a broader role for CCT in protein folding.
      Overall, our results suggest that efficient chaperone-mediated tubulin biogenesis
      is essential in C. elegans, owing to the critical role of the microtubule
      cytoskeleton in metazoan development.

PMID- 18062953
TI  - Molecular separation of two signaling pathways for the receptor, Notch.
AB  - Notch is required for many aspects of cell fate specification and morphogenesis
      during development, including neurogenesis and axon guidance. We here provide
      genetic and biochemical evidence that Notch directs axon growth and guidance in
      Drosophila via a "non-canonical", i.e. non-Su(H)-mediated, signaling pathway,
      characterized by association with the adaptor protein, Disabled, and Trio, an
      accessory factor of the Abl tyrosine kinase. We find that forms of Notch lacking
      the binding sites for its canonical effector, Su(H), are nearly inactive for the
      cell fate function of the receptor, but largely or fully active in axon
      patterning. Conversely, deletion from Notch of the binding site for Disabled
      impairs its action in axon patterning without disturbing cell fate control.
      Finally, we show by co-immunoprecipitation that Notch protein is physically
      associated in vivo with both Disabled and Trio. Together, these data provide
      evidence for an alternate Notch signaling pathway that mediates a postmitotic,
      morphogenetic function of the receptor.

PMID- 18062954
TI  - The coxsackie and adenovirus receptor (CAR) is required for renal epithelial
      differentiation within the zebrafish pronephros.
AB  - The coxsackie and adenovirus receptor (CAR) is a member of the immunoglobulin
      superfamily and a component of vertebrate tight junctions. CAR protein is widely
      expressed in fish and mammals in organs of epithelial origin suggesting possible
      functions in epithelial biology. In order to gain insight into its function, we
      knocked the CAR gene down in zebrafish using antisense morpholinos. We identified
      a requirement for CAR in the terminal differentiation of glomerular podocytes and
      pronephric tubular epithelia. Podocytes differentiate in CAR morphants but are
      not able to elaborate a regularly patterned architecture of foot processes. In
      the tubules, CAR was required for the apposition of plasma membranes from
      adjacent epithelial cells but did not appear to be necessary for the formation of
      tight junctions. Additionally, tubular epithelia lacking CAR were not able to
      elaborate apical brush border microvilli. These results establish a requirement
      for CAR in the terminal differentiation of renal glomerular and tubular cell
      types.

PMID- 18062956
TI  - Cortical and cytoplasmic flows driven by actin microfilaments polarize the
      cortical ER-mRNA domain along the a-v axis in ascidian oocytes.
AB  - Cellular mechanisms generating the polarized redistribution of maternal Type I
      postplasmic/PEM mRNAs in ascidian oocytes remain unknown. We have previously
      shown that PEM-1 mRNA is associated with a network of rough cortical Endoplasmic
      Reticulum (cER) polarized along the animal-vegetal (a-v) axis forming a cER-mRNA
      domain in mature oocytes. We now investigate the a-v polarization of this cER
      mRNA domain during meiotic maturation using H. roretzi and C. intestinalis. We
      show that the cER and Hr-PEM-1 aggregate as interconnected cortical patches at
      the cell periphery before maturation, which uniformly spread out during
      maturation and form a reticulated organization enriched in the vegetal hemisphere
      at the end of maturation. Time-lapse video recordings coupled with
      micromanipulations reveal that stereotyped surface, cortical and cytoplasmic
      flows accompany the vegetal shift of the cER-mRNA domain and mitochondria-rich
      myoplasm. Treatments with cytochalasin B and nocodazole indicate that both
      polarization of the cER-mRNA domain and mitochondria-rich myoplasm and cortical
      and cytoplasmic flows depend on actin cytoskeleton, but not microtubules. Using
      cortical fragments prepared from maturing oocytes coupled with high resolution
      immuno/in situ localization, we have further analyzed the effects of these
      inhibitors on the reorganizations the cER network and Hr-PEM-1 mRNA. We show that
      before maturation starts, Hr-PEM-1 mRNAs are already associated with the cER, and
      actin cytoskeleton inhibitors disturb their association. Finally, we hypothesize
      that Germinal Vesicle Break Down (GVBD) triggers an actomyosin-dependent cortical
      flow which directs the a-v polarization of ascidian oocytes.

PMID- 18062955
TI  - Vascular sprout formation entails tissue deformations and VE-cadherin-dependent
      cell-autonomous motility.
AB  - Embryonic and fetal vascular sprouts form within constantly expanding tissues.
      Nevertheless, most biological assays of vascular spouting are conducted in a
      static mechanical milieu. Here we study embryonic mouse allantoides, which
      normally give raise to an umbilical artery and vein. However, when placed in
      culture, allantoides assemble a primary vascular network. Unlike other in vitro
      assays, allantoic primordial vascular cells are situated on the upper surface of
      a cellular layer that is engaged in robust spreading motion. Time-lapse imaging
      allows quantification of primordial vascular cell motility as well as the
      underlying mesothelial tissue motion. Specifically, we calculate endothelial cell
      autonomous motion by subtracting the tissue-level mesothelial motion from the
      total endothelial cell displacements. Formation of new vascular polygons is
      hindered by administration of function-blocking VE-cadherin antibodies. Time
      lapse recordings reveal that (1) cells at the base of sprouts normally move
      distally "over" existing sprout cells to form new tip-cells; and (2) loss of VE
      cadherin activity prevents this motile behavior. Thus, endothelial cell-cell
      adhesion-based motility is required for the advancement of vascular sprouts
      within a moving tissue environment. To the best of our knowledge, this is the
      first study that couples endogenous tissue dynamics to assembly of vascular
      networks in a mammalian system.

PMID- 18062957
TI  - Proliferation and patterning are mediated independently in the dorsal spinal cord
      downstream of canonical Wnt signaling.
AB  - Canonical Wnt signaling can regulate proliferation and patterning in the
      developing spinal cord, but the relationship between these functions has remained
      elusive. It has been difficult to separate the distinct activities of Wnts
      because localized changes in proliferation could conceivably alter patterning,
      and gain and loss of function experiments have resulted in both types of defects.
      To resolve this issue we have investigated canonical Wnt signaling in the
      zebrafish spinal cord using multiple approaches. We demonstrate that Wnt
      signaling is required initially for proliferation throughout the entire spinal
      cord, and later for patterning dorsal progenitor domains. Furthermore, we find
      that spinal cord patterning is normal in embryos after cell division has been
      pharmacologically blocked. Finally, we determine the transcriptional mediators of
      Wnt signaling that are responsible for patterning and proliferation. We show that
      tcf7 gene knockdown results in dorsal patterning defects without decreasing the
      mitotic index in dorsal domains. In contrast, tcf3 gene knockdown results in a
      reduced mitotic index without affecting dorsal patterning. Together, our work
      demonstrates that proliferation and patterning in the developing spinal cord are
      separable events that are regulated independently by Wnt signaling.

PMID- 18062958
TI  - Integration of embryonic and fetal skeletal myogenic programs at the myosin light
      chain 1f/3f locus.
AB  - The genetic control of skeletal muscle differentiation at the onset of myogenesis
      in the embryo is relatively well understood compared to the formation of muscle
      during the fetal period giving rise to the bulk of skeletal muscle fibers at
      birth. The Mlc1f/3f (Myl1) locus encodes two alkali myosin light chains, Mlc1f
      and Mlc3f, from two promoters that are differentially regulated during
      development. The Mlc1f promoter is active in embryonic, fetal and adult fast
      skeletal muscle whereas the Mlc3f promoter is upregulated during fetal
      development and remains on in adult fast skeletal muscle. Two enhancer elements
      have been identified at the mammalian Mlc1f/3f locus, a 3' element active at all
      developmental stages and an intronic enhancer activated during fetal development.
      Here, using transgenesis, we demonstrate that these enhancers act combinatorially
      to confer the spatial, temporal and quantitative expression profile of the
      endogenous Mlc3f promoter. Using double reporter transgenes we demonstrate that
      each enhancer can activate both Mlc1f and Mlc3f promoters in vivo, revealing
      enhancer sharing rather than exclusive enhancer-promoter interactions. Finally,
      we demonstrate that the fetal activated enhancer contains critical E-box myogenic
      regulatory factor binding sites and that enhancer activation is impaired in vivo
      in the absence of myogenin but not in the absence of innervation. Together our
      observations provide insights into the regulation of fetal myogenesis and the
      mechanisms by which temporally distinct genetic programs are integrated at a
      single locus.

PMID- 18062960
TI  - Land use effects in groundwater composition of an alluvial aquifer (Trussu River,
      Brazil) by multivariate techniques.
AB  - Multivariate statistical techniques, cluster analysis (CA) and factor
      analysis/principal component analysis (FA/PCA), were applied to analyze the
      similarities or dissimilarities among the sampling sites to identify spatial and
      temporal variations in water quality and sources of contamination (natural and
      anthropogenic). The aquifer under study is supplied by the Trussu River, which
      has a general direction from west to east, within Iguatu County, Ceara, Brazil.
      Groundwater samples were collected in four shallow wells, located at the Trussu
      River alluvial, from October 2002 to February 2004. The samples were analyzed for
      13 parameters: pH, electrical conductivity (EC), Na, Ca, Mg, K, Cl, HCO(3),
      PO(4), NH(4)-N, NO(3)-N, SO(4), and sodium adsorption ratio (SAR). Two zones were
      very well differentiated based on cluster analysis results, and implied a
      relation to geographic position and time variation. One zone called UL-upland
      region-corresponds to upland of studied area, used mainly for irrigation and
      livestock activities. The other zone called DL-downland region-corresponds to the
      region downstream and is occupied by human settlements. These results may be used
      to reduce the number of samples analyzed both in space and time, without too much
      loss of information. Three major independent factors that define water quality in
      the UL region and four in DL region were identified in the PCA. At both regions,
      rotated component (RC) loadings identified that the variables responsible for
      water quality composition are mainly related to soluble salts variables (natural
      process) and nutrients (high loads of NO(3)-N, NH(4)-N), expressing anthropogenic
      activities. RC also revealed that hydrochemical processes were the major factors
      responsible for water quality.

PMID- 18062959
TI  - Worming out the biology of Runx.
AB  - Runx family transcription factors have risen to prominence over the last few
      years because of the increasing evidence implicating them as key regulators of
      the choice between cell proliferation and differentiation during development and
      carcinogenesis. Runx factors have been found to be involved in diverse
      developmental processes, ranging from hematopoiesis to neurogenesis, and are
      increasingly being linked with various human cancers. In this review, we examine
      the case for Runx factors as key regulators of cell proliferation in various
      developmental situations, a role that predisposes Runx mutations as causative
      agents in oncogenesis. We discuss the evidence that Runx factors regulate, and
      are regulated by, core components of the cell cycle machinery, and focus our
      attention on the solo Runx gene, rnt-1, in Caenorhabditis elegans, an organism
      that we feel has much to offer the Runx field.

PMID- 18062961
TI  - Blocking melanin-concentrating hormone MCH1 receptor affects rat sleep-wake
      architecture.
AB  - Melanin-concentrating hormone (MCH) is a hypothalamic peptide that centrally
      regulates food intake, energy balance and emotion. Interestingly, MCH and melanin
      concentrating hormone MCH(1) receptors are distributed in brain areas known to
      regulate vigilance states. Effects of subcutaneous administration of two
      selective melanin-concentrating hormone MCH(1) receptor antagonists, labeled A
      and B were examined over a broad dose range (1, 3, 10, 20, 40 mg/kg) on rat sleep
      wake architecture. Both compounds have a nanomolar antagonist activity at
      recombinant human melanin-concentrating hormone MCH(1) receptor (IC(50)=44.1+/
      6.1 nM and 26.6+/-5.4 nM, respectively) and potently inhibited the MCH-induced
      mobilization of [Ca(2+)] (IC(50) 29.1+/-8.1 nM and 10.5+/-4.1 nM, respectively).
      The selectivity of both compounds was further confirmed on a panel of receptors,
      transporters and channels. In vivo, both compounds dose-dependently decreased
      deep sleep primarily by decreasing the mean duration of episodes during the first
      4 h post-administration. In parallel, REM sleep and intermediate stage sleep were
      decreased while active and passive waking increased. Deep sleep and REM sleep
      onset latencies were significantly prolonged at higher doses. No homeostatic
      rebound of deep sleep was observed, while a tendency for recovery of REM sleep
      was found during subsequent dark phase. Together, the results support a role of
      the melanin-concentrating hormone MCH(1) receptor in the regulation of deep slow
      wave sleep-REM sleep cycle. Therapeutic application of melanin-concentrating
      hormone MCH(1) receptor-inhibiting agents should take into account the
      significant decreases in deep sleep without recovery as these may interfere with
      sleep dependent memory consolidation.

PMID- 18062962
TI  - Increased severity of alcoholic liver injury in female verses male rats: a
      microarray analysis.
AB  - Alcoholic liver disease (ALD) is an increasingly recognized condition that may
      progress to end-stage liver disease. In addition to alcohol consumption, genetic
      factors, dietary fatty acids, gender and viral infection potentiate the severity
      of alcoholic liver injury. In humans, significant gender differences in
      susceptibility to ALD are observed. In the intragastric infusion rat model of
      ALD, female rats developed more severe liver injury than males. To understand the
      effect of gender on the development of more severe ALD in female rats, we
      performed a microarray based expression profiling of genes in rats fed with fish
      oil and ethanol diet. A large number of genes showed significant changes in
      female livers compared to males. The upregulated genes in female liver were
      involved in proteosome endopeptidase activity, catalytic activity, lipid
      metabolism, alcohol metabolism, mitochondrial and oxidoreductase activity. The
      downregulated genes were involved in oxidoreductase activity, chaperone activity,
      and electron transport activity in the female liver as demonstrated by biological
      theme analysis. Ingenuity computational pathway analysis tools were used to
      identify specific regulatory networks of genes operative in promoting liver
      injury. These networks allowed us to identify a large cluster of genes involved
      in lipid metabolism, development, cellular growth and proliferation, apoptosis,
      carcinogenesis and various signaling pathways. Genes listed in this article that
      were significantly increased or decreased (expression two fold or more) were
      assigned to pathological functional groups and reviewed for relevance to
      establish hypotheses of potential mechanisms involved in ALD in female liver
      injury.

PMID- 18062963
TI  - Mutationally activated K-ras 4A and 4B both mediate lung carcinogenesis.
AB  - To examine the roles of endogenous K-ras 4A and K-ras 4B splice variants in
      tumorigenesis, murine lung carcinogenesis was induced by N-methyl-N-nitrosourea
      (MNU), which causes a K-ras mutation (G12D) that jointly affects both isoforms.
      Compared with age-matched K-ras(tmDelta4A/-) mice (where tumours can express
      mutationally activated K-ras 4B only), tumour number and size were significantly
      higher in K-ras(+/-) mice (where tumours can also express mutationally activated
      K-ras 4A), and significantly lower in K-ras(tmDelta4A/tmDelta4A) mice (where
      tumours can express both wild-type and activated K-ras 4B). MNU induced
      significantly more, and larger, tumours in wild-type than K
      ras(tmDelta4A/tmDelta4A) mice which differ in that only tumours in wild-type mice
      can express wild-type and activated K-ras 4A. Lung tumours in all genotypes were
      predominantly papillary adenomas, and tumours from K-ras(+/-) and K
      ras(tmDelta4A/-) mice exhibited phospho-Erk1/2 and phospho-Akt staining. Hence
      (1) mutationally activated K-ras 4B is sufficient to activate the
      Raf/MEK/ERK(MAPK) and PI3-K/Akt pathways, and initiate lung tumorigenesis, (2)
      when expressed with activated K-ras 4B, mutationally activated K-ras 4A further
      promotes lung tumour formation and growth (both in the presence and absence of
      its wild-type isoform) but does not affect either tumour pathology or
      progression, and (3) wild-type K-ras 4B, either directly or indirectly, reduces
      tumour number and size.

PMID- 18062964
TI  - Intracellular co-localization of trypsin-2 and matrix metalloprotease-9: possible
      proteolytic cascade of trypsin-2, MMP-9 and enterokinase in carcinoma.
AB  - Tumor-associated trypsin-2 and matrix metalloprotease-9 (MMP-9) are associated
      with cancer, particularly with invasive squamous cell carcinomas. They require
      activation for catalytical competence via proteolytic cascades. One cascade is
      formed by enterokinase, trypsin-2 and MMP-9; enterokinase activates trypsinogen-2
      to trypsin-2, which is an efficient proMMP-9 activator. We describe here that
      oral squamous cell carcinomas express all members of this cascade: MMP-9, trypsin
      2 and enterokinase. The expression of enterokinase in a carcinoma cell line not
      derived from the duodenum was shown here for the first time. Enterokinase
      directly cleaved proMMP-9 at the Lys65-Ser66 site, but failed to activate it in
      vitro. We demonstrated by confocal microscopy that MMP-9 and trypsin-2 co
      localized in intracellular vesicles of the carcinoma cells. This co-localization
      of trypsin-2 and MMP-9 resulted in intracellular proMMP-9 processing that
      represented fully or partially activated MMP-9. However, although both proteases
      were present also in various bone tumor tissues, MMP-9 and trypsin-2 never co
      localized at the cellular level in these tissues. This suggests that the
      intracellular vesicular co-localization, storage and possible activation of these
      proteases may be a unique feature for aggressive epithelial tumors, such as
      squamous cell carcinomas, but not for tumors of mesenchymal origin.

PMID- 18062966
TI  - Culture-induced increase in alpha integrin subunit expression in retinal pigment
      epithelium is important for improved resurfacing of aged human Bruch's membrane.
AB  - The purpose of this study was to examine the change in integrin expression in
      adult human retinal pigment epithelium (RPE) after culturing and to characterize
      the role of integrins in RPE adhesion to aged submacular human Bruch's membrane.
      Expression of alpha integrin subunits 1 through 6 in adult RPE cells, cultured or
      uncultured, was examined by reverse transcription/real-time polymerase chain
      reaction (PCR) and Western blotting. RPE was cultured on bovine corneal
      endothelial cell-secreted extracellular matrix (BCE-ECM). The role of alpha
      integrin subunits in RPE attachment was examined by immunofluorescent
      localization of these subunits at sites of focal adhesions in cultured adult RPE
      attached to laminin or collagen-I-coated culture dishes. Additionally, the effect
      of function-blocking antibodies to alpha integrin subunits on RPE attachment to
      laminin, collagen I, and aged submacular human Bruch's membrane was determined.
      Cultured adult RPE had increased expression of alpha1-5 integrin subunits by PCR
      compared to uncultured RPE. Western blots showed that alpha2, 3, and 5 subunit
      levels were low or absent in uncultured adult RPE. Cultured adult RPE had a
      substantially higher expression of these integrins. Alpha 1-3 subunits co
      localized with phosphorylated focal adhesion kinase (FAK) at focal adhesions in
      RPE cells spread on laminin. Only alpha2 and alpha3 co-localized with
      phosphorylated FAK in focal adhesions of RPE on collagen I. Using function
      blocking antibodies, blocking alpha1 subunit singly or in combination with alpha2
      and/or alpha3 significantly decreased RPE adhesion to laminin. Blocking alpha1
      and alpha2 or blocking alpha1, alpha2, and alpha3 subunits significantly
      decreased RPE adhesion to collagen I. Compared to controls, significantly fewer
      RPE cells were able to spread on aged submacular human Bruch's membrane when
      alpha1-6 integrin subunits were blocked. These results indicate that alpha 1-5
      subunits that are upregulated by culturing on BCE-ECM are necessary for RPE
      attachment to aged submacular human Bruch's membrane. Relative lack of these
      integrin subunits in uncultured adult RPE may be responsible for poor resurfacing
      of aged submacular human Bruch's membrane by these cells.

PMID- 18062965
TI  - The inhibition of tube formation in a collagen-fibrinogen, three-dimensional gel
      by cleaved kininogen (HKa) and HK domain 5 (D5) is dependent on Src family
      kinases.
AB  - Cleaved high molecular weight kininogen (HKa), as well as its domain 5 (D5),
      inhibits migration and proliferation induced by angiogenic factors and induces
      apoptosis in vitro. To study its effect on tube formation we utilized a collagen
      fibrinogen, three-dimensional gel, an in vitro model of angiogenesis. HKa, GST-D5
      and D5 had a similar inhibitory effect of tube length by 90+/-4.5%, 86+/-5.5% and
      77+/-12.9%, respectively. D5-derived synthetic peptides: G440-H455 H475-H485 and
      G486-K502 inhibited tube length by 51+/-3.7%, 54+/-3.8% and 77+/-1.7%,
      respectively. By a comparison of its inhibitory potency and its sequences, a
      functional sequence of HKa was defined to G486-G496. PP2, a Src family kinase
      inhibitor, prevented tube formation in a dose-dependent manner (100-400 nM), but
      PP3 at 5 microM, an inactive analogue of PP2, did not. HKa and D5 inhibited Src
      416 phosphorylation by 62+/-12.3% and 83+/-6.1%, respectively. The C-terminal Src
      kinase (Csk) inhibits Src kinase activity. Using a siRNA to Csk, expression of
      Csk was down-regulated by 86+/-7.0%, which significantly increased tube length by
      27+/-5.8%. The addition of HKa and D5 completely blocked this effect. We further
      showed that HKa inhibited Src family kinase activity by disrupting the complex of
      uPAR, alphavbeta3 integrin and Src. Our results indicate that the anti-angiogenic
      effect of HKa and D5 is mediated at least in part through Src family kinases and
      identify a potential novel target for therapeutic inhibition of
      neovascularization in cancer and inflammatory arthritis.

PMID- 18062967
TI  - Corticosterone metabolites in blue tit and pied flycatcher droppings: effects of
      brood size, ectoparasites and temperature.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis of birds induces the secretion of
      corticosterone (CORT) as a response to different ecological variables. In this
      study we tested experimentally if manipulations of brood size or ectoparasitism
      led to subsequent differences in the concentration of excreted CORT metabolites
      of adult and nestling blue tits (Cyanistes caeruleus). No significant effect of
      the manipulation of brood size was detected in adults or nestlings. No
      significant effect of ectoparasitism was detected in males or nestlings, although
      females from uninfested nests showed lower concentrations of excreted CORT
      metabolites. In addition, we analysed if weather conditions had an influence on
      the concentration of excreted CORT metabolites of blue tits and pied flycatchers
      (Ficedula hypoleuca) breeding in the same forest. We detected no effect of
      weather conditions on adults, but nestlings of both species showed a negative
      correlation between their excreted CORT metabolites and the average mean
      temperatures they were subjected to during their growth. This effect was not
      found in blue tits in a colder year, suggesting that the sensitivity of the HPA
      axis to ambient temperature may be subjected to interannual variation. Moreover,
      we found a positive effect of the maximum temperature on the day of sampling on
      the concentration of CORT metabolites of blue tit nestlings in one of the years.
      These results suggest that weather conditions may act as environmental stressors
      to which the HPA axis of blue tit and pied flycatcher nestlings may be sensitive.

PMID- 18062968
TI  - Autopsies following death due to traumatic injuries in The Netherlands: an
      evaluation of current practice.
AB  - INTRODUCTION: Because of a steady decline in the number of autopsies following
      death due to traumatic injuries, valuable information concerning possible missed
      injuries and potential improvements in management is lost. This retrospective
      study describes current practice in the Amsterdam region of the Netherlands
      regarding such autopsies, and their rates. METHOD: The current protocols for
      autopsies were reviewed. Data from government databases and hospitals for the
      year 2005 were collected. For all patients included that died an unnatural death
      due to traumatic injury, causes of death and recommendations for autopsy were
      reviewed. The number of clinical and medico-legal autopsies was determined.
      RESULTS: Of 872 registered unnatural deaths, 414 were due to traumatic injuries;
      63% of these died before reaching hospital and 37% died in hospital. There were
      more male deaths, and average age was 54 years. In 23% an autopsy was advised by
      the medical examiners, more often for pre-hospital deaths. The rate of autopsies
      was 46% when advice was given for a medico-legal autopsy. CONCLUSION: The rates
      of both medico-legal and clinically desirable autopsies are very low. Currently,
      the system in Amsterdam focuses mainly on the former, and the latter with its
      attendant educational aspects is largely ignored. The role of the government
      should be expanded to optimise the autopsy system in unnatural deaths following
      traumatic injuries.

PMID- 18062969
TI  - Factors influencing discharge location following hip fracture.
AB  - INTRODUCTION: Outcome measures following hip fracture usually consider morbidity
      and mortality following injury.(5) Few studies have looked at post injury
      discharge location as an outcome measure following hip fracture. Discharging
      patients to a different location frequently delays discharge whilst the necessary
      social arrangements are made. Early identification of these patients could reduce
      these delays. The aim of this study was to determine factors influencing
      discharge location following hip fracture. METHODS: Three thousand two hundred
      and forty consecutive patients were admitted to our centre with a fractured neck
      of femur. Data was prospectively collected by independent audit clerks on a
      standardised proforma. Our outcome measure was whether the patient was discharged
      from hospital either to their place of normal residence or to an alternative
      location. Factors influencing discharge location were identified using
      multivariate logistic regression analysis. RESULTS: Increasing age was associated
      with increasing risk of requiring discharge to an alternative location (DAL)
      (p<0.001). This risk rose from 13% in the sixth decade by approximately 10% every
      additional decade. Males were 2.5 times more likely than females to require DAL.
      Patients who were more independent prior to injury were less likely to require
      DAL. Patients who sustained their injury whilst in hospital were 2.3 times more
      likely to require DAL compared to those who fell in their own homes. CONCLUSION:
      The following risk factors are associated with increased risk of requiring
      discharge to an alternative location: (1) pre-injury dependence, (2) increasing
      age, (3) male sex, (4) injury sustained whilst in hospital. Early identification
      of patients requiring DAL could reduce inpatient delays.

PMID- 18062970
TI  - Ethical and legal conundrums of postmodern procreation.

PMID- 18062972
TI  - Functional expression of ribozymes in Apicomplexa: towards exogenous control of
      gene expression by inducible RNA-cleavage.
AB  - The ability to control expression of a specific gene is a prerequisite to
      understand the function of essential genes. Many gene regulation systems operate
      on the transcriptional level by employing heterologous cis- and trans-acting
      elements. Recently, novel approaches employing autocatalytic RNA have been
      reported for different organisms. Here we show specific downregulation of gene
      expression in the apicomplexan parasites Toxoplasma gondii and Plasmodium
      falciparum, employing self-cleaving ribozymes integrated into the transcriptional
      unit of different genes. Moreover, we demonstrate the potential to specifically
      upregulate reporter gene expression by employment of the recently identified
      ribozyme inhibitor toyocamycin. At the RNA-level, we were able to significantly
      stabilise the mRNA in T. gondii. Furthermore we show that the adenosine analogue
      toyocamycin needs to be phosphorylated by adenosine kinase in order to act as an
      inhibitor for hammerhead ribozymes, since neither upregulation of reporter gene
      expression nor a toxic effect of toyocamycin can be detected in parasites that do
      not express the enzyme adenosine kinase.

PMID- 18062974
TI  - Vaccination with a Plasmodium chabaudi adami multivalent DNA vaccine cross
      protects A/J mice against challenge with P. c. adami DK and virulent Plasmodium
      chabaudi chabaudi AS parasites.
AB  - A current goal of malaria vaccine research is the development of vaccines that
      will cross-protect against multiple strains of malaria. In the present study, the
      breadth of cross-reactivity induced by a 30K multivalent DNA vaccine has been
      evaluated in susceptible A/J mice (H-2a) against infection with the Plasmodium
      chabaudi adami DK strain and a virulent parasite subspecies, Plasmodium chabaudi
      chabaudi AS. Immunized A/J mice were significantly protected against infection
      with both P. c. adami DK (31-40% reduction in cumulative parasitemia) and P. c.
      chabaudi AS parasites, where a 30-39% reduction in cumulative parasitemia as well
      as enhanced survival was observed. The 30K vaccine-induced specific IFN-gamma
      production by splenocytes in response to native antigens from both P. c. chabaudi
      AS and P. c. adami DK. Specific antibodies reacting with surface antigens
      expressed on P. c. adami DS and P. c. chabaudi AS infected red blood cells, and
      with opsonizing properties, were detected. These results suggest that multivalent
      vaccines encoding conserved antigens can feasibly induce immune cross-reactivity
      that span Plasmodium strains and subspecies and can protect hosts of distinct
      major histocompatibility complex haplotypes.

PMID- 18062973
TI  - Genetic characterization and phylogenetic position of Echinococcus felidis
      (Cestoda: Taeniidae) from the African lion.
AB  - Echinococcus felidis had been described in 1937 from African lions, but was later
      included in Echinococcus granulosus as a subspecies or a strain. In the absence
      of any genetic characterization, most previous records of this taxon from a
      variety of large African mammals remained unconfirmed due to the lack of
      diagnostic criteria and the possible confusion with the sympatric E. granulosus
      sensu stricto, Echinococcus ortleppi and Echinococcus canadensis. In this study,
      we obtained taeniid eggs from lion feces in Uganda and amplified DNA from
      individual eggs. Mitochondrial and nuclear DNA sequences showed similarities with
      those of other Echinococcus spp., but high values of percentage divergence of
      mitochondrial genes indicated the presence of a distinct species. In a second
      step, we compared this material with the preserved specimens of adult E.
      granulosus felidis, which had been identified morphologically approximately 40
      years ago in South Africa. All DNA fragments (<200 bp) that could be amplified
      from the adults showed 100% similarity with the Ugandan material. In the
      phylogenetic tree of Echinococcus which was constructed from the mitochondrial
      genes, E. felidis is positioned as a sister taxon of E. granulosus sensu stricto.
      The data obtained will facilitate the development of diagnostic tools necessary
      to study the epidemiology of this enigmatic parasite.

PMID- 18062975
TI  - Polymorphisms in the estrogen receptor alpha gene and endothelial function in
      resistance and conduit arteries in the elderly.
AB  - BACKGROUND: Prior evidence suggests an important role for estrogen in the
      regulation of endothelium-dependent vasodilation, but the mechanisms modulating
      this are not known. Our aim was to examine the relations of single nucleotide
      polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) to endothelium
      dependent vasodilation. METHODS: We evaluated 959 70-year-old participants (51%
      men) of the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS)
      study, using invasive forearm technique with intra-brachial infusion of
      acetylcholine (EDV; reflecting vasodilation in resistance arteries), and brachial
      artery ultrasound to assess flow-mediated vasodilation (FMD; reflecting
      vasodilation in conduit arteries). We genotyped 25 common SNPs in the ESR1 gene,
      and related them to EDV and FMD using multivariable linear regression, adjusting
      for sex and other potential confounders, such as major cardiovascular risk
      factors and medications. Haplotypes were estimated using the PHASE software.
      RESULTS: We observed an association between rs1709183 in the ESR1 gene and EDV
      (nominal P=0.0012), with a lower EDV in carriers of the minor allele (C). This
      association remained significant after adjustment for multiple testing (empirical
      P=0.031, obtained using bootstrap re-sampling). Two ESR1 haplotypes in the block
      containing rs1709183 were associated with EDV (individual haplotype P=0.0015 and
      P=0.025); the directions of effect were consistent with individual SNP analyses.
      FMD was not associated with any of the ESR1 SNPs. CONCLUSIONS: In our community
      based study of elderly, a polymorphism in the estrogen receptor alpha gene was
      associated with endothelium-dependent vasodilation in resistance, but not conduit
      arteries. Our findings should stimulate further exploration in other settings.

PMID- 18062976
TI  - Effects of plant stanol esters on serum cholesterol concentrations, relative
      markers of cholesterol metabolism and endothelial function in type 1 diabetes.
AB  - We investigated the effect of plant stanol esters (STAEST) on serum total and LDL
      cholesterol concentrations and endothelial function in subjects with type 1
      diabetes (T1D). In addition, the changes in the relative serum markers of
      cholesterol metabolism were recorded. In a parallel, randomized, double-blind
      study the intervention group (n = 11) consumed STAEST spread (2g/day stanols) and
      the control group (n=8) the same spread containing no added stanols for 12 weeks.
      At baseline, brachial artery diameter was negatively correlated with serum HDL
      cholesterol concentration (r = -0.476, P < 0.05), but not with total or LDL
      cholesterol concentrations or serum non-cholesterol sterol ratios to cholesterol.
      Flow-mediated dilatation was positively associated with serum absorption marker
      ratios to cholesterol, significantly so with the sitosterol ratio (r = 0.467, P <
      0.05). During the intervention, serum total and LDL cholesterol concentrations
      were reduced by 4.9 and 6.9% from baseline in the STAEST group, and by 10.8 and
      16.1% from controls, respectively (P < 0.05 for all). No significant changes in
      HDL cholesterol and serum triglyceride concentrations were found. The STAEST
      consumption reduced serum campesterol and sitosterol ratios by 17-21% (P<0.05)
      from baseline, but the relative serum synthesis markers were not changed.
      Brachial artery diameter and flow-mediated dilatation did not change during the
      investigation. In conclusion, STAEST significantly reduced serum total and LDL
      cholesterol concentrations and serum plant sterol ratios without affecting HDL
      and triglyceride concentrations in subjects with T1D. STAEST had no effect on
      endothelial function.

PMID- 18062978
TI  - Local administration of interleukin-1 receptor antagonist inhibits deterioration
      of mechanical properties of the stress-shielded patellar tendon.
AB  - We previously found that interleukin (IL)-1beta is over-expressed in the
      fibroblasts of the stress-shielded patellar tendon using a stress-shielding model
      [Uchida, H., Tohyama, H., Nagashima, K., Ohba, Y., Matsumoto, H., Toyama, Y.,
      Yasuda, K., 2005. Stress deprivation simultaneously induces over-expression of
      interleukin-1beta, tumor necrosis factor-alpha, and transforming growth factor
      beta in fibroblasts and mechanical deterioration of the tissue in the patellar
      tendon. Journal of Biomechanics 38(4), 791-798.]. Therefore, IL-1beta may play a
      role in tendon deterioration in response to stress deprivation. This study was
      conducted to clarify the effects of local administration of interleukin-1
      receptor antagonist (IL-1ra) on the mechanical properties of the stress-shielded
      patellar tendon as well as the tendon fascicles harvested from it. Twenty-six
      mature rabbits were equally divided into Groups IL-1ra and PBS after the right
      patellar tendon underwent the stress-shielding treatment, which completely
      released the patellar tendon from tension by stretching the flexible wire
      installed between the patella and the tibial tubercle. In Group IL-1ra, IL-1ra
      was injected between the patellar tendon and the infra-patellar fat pad. In Group
      PBS, phosphate-buffered saline was injected in the same manner as IL-1ra. All
      rabbits were evaluated at 3 weeks after the stress-shielding procedure. The
      tangent modulus and the tensile strength of the patellar tendons were
      significantly greater in Group IL-1ra than in Group PBS, while there was no
      significant difference in the strain at failure between Groups IL-1ra and PBS.
      Concerning the mechanical properties of the fascicles harvested from the patellar
      tendon, however, we could not detect any significant differences in the tangent
      modulus, tensile strength, or strain at failure between Groups IL-1ra and PBS.
      The present study suggested that IL-1 plays an important role in the
      deterioration of the mechanical properties of the patellar tendon in response to
      stress shielding and that IL-1 does not affect the fascicles themselves.

PMID- 18062971
TI  - Stage-specific gene expression in Teladorsagia circumcincta (Nematoda:
      Strongylida) infective larvae and early parasitic stages.
AB  - Suppression subtractive hybridisation was used to enrich genes expressed in a
      stage-specific manner in infective, exsheathed L3s (xL3) versus early L4s of the
      ovine nematode, Teladorsagia circumcincta prior to gene expression profiling by
      microarray. The 769 cDNA sequences obtained from the xL3-enriched library
      contained 361 unique sequences, with 292 expressed sequence tags (ESTs) being
      represented once ("singletons") and 69 sequences which were represented more than
      once (overlapping and non-overlapping "contigs"). The L4-enriched EST dataset
      contained 472 unique sequences, with 314 singletons and 158 contigs. Of these 833
      sequences, 85% of the xL3 sequences and 86% of the L4 sequences exhibited
      homology to known genes or ESTs derived from other species of nematode.
      Quantitative differential expression (P<0.05) was demonstrated for 563 (68%) of
      the ESTs by microarray. Within the L3-specific dataset, more than 30% of the
      transcripts represented the enzyme, guanosine-5'-triphosphate (GTP)
      cyclohydrolase, which is the first and rate-limiting enzyme of the
      tetrahydrobiopterin synthesis pathway and may be involved in critical elements of
      larval development. In L4s, proteolytic enzymes were highly up-regulated, as were
      collagens and a number of previously characterised secretory proteins, reflecting
      the rapid growth of these larvae in abomasal glands. Nucleotide sequence data
      reported in this paper are available in the EMBL, GenBank and DDJB databases
      under accession numbers AM 743198-AM 744942.

PMID- 18062979
TI  - Determinants of difference in leg stiffness between endurance- and power-trained
      athletes.
AB  - Understanding the leg and joint stiffness during human movement would provide
      important information that could be utilized for evaluating sports performance
      and for injury prevention. In the present study, we examined the determinants of
      the difference in the leg stiffness between the endurance-trained and power
      trained athletes. Seven distance runners and seven power-trained athletes
      performed in-place hopping, matching metronome beats at 3.0 and 1.5Hz. Leg and
      joint stiffness were calculated from kinetic and kinematics data.
      Electromyographic activity (EMG) was recorded from six leg muscles. At both
      hopping frequencies, the power-trained athletes demonstrated significantly higher
      leg stiffness than the distance runners. Hip, knee, and ankle joints were
      analyzed for stiffness and touchdown angles. Ankle stiffness was significantly
      greater in the power-trained athletes than the distance runners at 3.0Hz as was
      knee stiffness at 1.5Hz. There was no significant difference in touchdown angle
      between the DR and PT groups at either hopping frequencies. When significant
      difference in EMG activity existed between two groups, it was always greater in
      the distance runners than the power-trained athletes. These results suggest that
      (1) the difference in leg stiffness between endurance-trained and power-trained
      athletes is best attributed to increased joint stiffness, and (2) the difference
      in joint stiffness between the two groups may be attributed to a lack of
      similarity in the intrinsic stiffness of the muscle-tendon complex rather than in
      altered neural activity.

PMID- 18062980
TI  - Comprehensive two-dimensional liquid chromatography with ultraviolet, evaporative
      light scattering and mass spectrometric detection of triacylglycerols in corn
      oil.
AB  - An improved comprehensive two-dimensional (LC x LC) HPLC system for the analysis
      of triacylglycerols was developed. In the first-dimension, a Ag(I)-coated cation
      exchanger (250 mm x 2.1 mm, 5 microm) was employed with a gradient from 100% MeOH
      to 6% MeCN in MeOH at 20 microL/min. Using a 10-way valve with two switching
      loops, 1 min sections of the first-dimension were introduced in the second
      dimension consisting of a 30 mm x 4.6 mm C18 (1.8 microm) column with an
      isocratic mobile phase of methanol-methyl tert-butyl ether (70:30) at 3.0 mL/min.
      As the second-dimension solvent was stronger than the first-dimension solvent,
      focusing in the second-dimension took place, leading to better separations than
      in previously reported analyses in which hexane was the main constituent of the
      first-dimension eluent. Compounds differing by 2 in their partition number were
      baseline separated in the second-dimension. Detection took place by UV at 210 nm,
      evaporative light scattering and (+)-atmospheric pressure chemical ionisation-MS
      with the latter giving the best results. Corn oil was investigated and 44
      compounds could be detected: 34 triacylglycerols (TAGs), 8 oxygenated TAGs, and 2
      TAGs containing a trans double bond. Data manipulation allowed the construction
      of contour plots and the automated calculation of the first- and second-dimension
      retention times and peak areas. Quantitative results are compared with a fatty
      acid methyl ester analysis, and with literature data.

PMID- 18062981
TI  - The ultimate band compression factor in gradient elution chromatography.
AB  - The equations predicting the ultimate time band compression factor, G=(t(R)
      t(F))/t(p) in linear gradient elution chromatography, for an infinitely narrow
      injection (injection time t(p)-->0) were derived for an ideal-model column
      (dispersionless chromatography, H=0) assuming the Linear Solvent Strength Model
      for the retention behavior of the analyte. Numerical solutions can readily be
      obtained when the LSSM model does not apply. The results can be generalized to
      any retained organic modifier (k'(A)) in the mobile phase. The stronger the
      retention of the organic modifier, the more effective the band compression.
      Dispersion in real chromatographic column (H not equal 0) affects the limits that
      can be reached in linear gradients but poorly in step gradients. Examples based
      on a conventional HETP of about 12 microm using a 5 microm particle packed column
      reveal that the best time compression factor that could be expected is twice the
      one predicted with an ideal column.

PMID- 18062982
TI  - Optimal experimental design in chromatography.
AB  - Many experimental programs in chromatography involve the estimation of a second
      order response surface. The paper focuses on the use of the methods of optimal
      experimental design to find efficient response surface designs. We give tables of
      the properties of designs with two, three and four factors. References are given
      to tables of designs and to SAS programs for their construction.

PMID- 18062983
TI  - Quality control in quantification of volatile organic compounds analysed by
      thermal desorption-gas chromatography-mass spectrometry.
AB  - This paper presents a detailed study on the calibration of a thermal desorption
      gas chromatography-mass spectrometry (TD-GC-MS)-based methodology for
      quantification of volatile organic compounds (VOCs) in gaseous and liquid
      samples. For the first time, it is documented to what extent three widely
      encountered problems affect precise and accurate quantification, and solutions to
      improve calibration are proposed. The first issue deals with the limited
      precision in MS quantification, as exemplified by high relative standard
      deviations (up to 40%, n=5) on response factors of a set of 69 selected VOCs in a
      volatility range from 16 Pa to 85 kPa at 298 K. The addition of [(2)H(8)]toluene
      as an internal standard, in gaseous or liquid phase, improves this imprecision by
      a factor of 5. Second, the matrix in which the standard is dissolved is shown to
      be highly important towards calibration. Quantification of gaseous VOCs loaded on
      a sorbent tube using response factors obtained with liquid standards results in
      systematic deviations of 40-80%. Relative response factors determined by the
      analysis of sorbent tubes loaded with both analytes and [(2)H(8)]toluene from
      liquid phase are shown to offer a reliable alternative for quantification of
      airborne VOCs, without need for expensive and often hardly available gaseous
      standards. Third, a strategy is proposed involving the determination of a
      relative response factor being representative for a group of analytes with
      similar functionalities and electron impact fragmentation patterns. This group
      method approach indicates to be useful (RSD approximately 10%) for quantifying
      analytes belonging to that class but having no standards available.

PMID- 18062984
TI  - Self-assembly of a dialkylurea gelator in organic solvents in the presence of
      centrifugal and shearing forces.
AB  - A novel dialkylurea gelator, 1-methyl-2,4-bis(N(')-octadecaneureido)benzene
      (designated as MBOB) was synthesized, which can turn some organic solvents into
      organogels at extremely low concentrations (<2 wt%). The (1)H NMR spectra of MBOB
      in solution (110 degrees C) and in the gel state (30 degrees C) indicate that
      intermolecular hydrogen bonding is the driving force for the self-assembly of
      MBOB. In the process of the self-assembly of MBOB, orientation of MBOB aggregates
      occurs under the influence of external fields, such as a centrifugal force and
      shearing force fields. The minimum gelation concentrations of MBOB in organic
      solvents under a centrifugal force field were significantly higher than those in
      the absence of a centrifugal force field, indicating a significant effect of the
      external field on the self-assembly of MBOB. Field emission scanning electron
      microscopy (FE-SEM) provided evidence for a significantly phase transition of the
      MBOB aggregates from an amorphous state in the absence of the external field to
      an oriented state under conditions of a centrifugal or shearing force during the
      gelation process. A self-assembled structure of MBOB is proposed based upon an X
      ray diffraction (XRD) analysis and a molecular simulation. DSC analysis of the
      organogels indicates that the phase transition temperature increased from 58.5
      degrees C in the absence of the external field to 63.3 degrees C under a
      centrifugal force field and 62.2 degrees C under a shearing force field. The
      enthalpy of the phase transition decreased from 3.1 J/g in the absence of an
      external field to 2.6 J/g under a centrifugal force field and 2.7 J/g under a
      shearing force field.

PMID- 18062985
TI  - Histological and lectin binding changes in the genital tract of mice infected
      with Tritrichomonas foetus.
AB  - An experimental murine model of bovine genital tritrichomonosis is described.
      Female mice were inoculated per vaginam with Tritrichomonas foetus and a sample
      of the study population was killed every 3 days up to 60 days post-infection.
      Microscopical changes in the reproductive organs were assessed and
      immunohistochemistry was used to detect T. foetus within these tissues. Lectin
      histochemistry was used to determine changes in the expression of carbohydrates
      within the reproductive mucosa. A range of microscopical changes were detected in
      the uterine endometrium by 10 days post-inoculation and these were associated
      with the presence of the protozoan. The endometrial changes included endometritis
      and ulceration, mucosal atrophy and glandular metaplasia, and were similar to
      those reported in naturally infected cows. Changes in lectin binding were
      recognized first in the vagina where there was increased binding of Ulex
      europaeus agglutinin-1 (UEA-1) which was maximal on day 16 post-inoculation.
      Within the uterus, there was increased binding of soy bean agglutinin (SBA) which
      was maximal on day 19 post-inoculation, and of peanut agglutinin (PNA) which was
      maximal on day 16 post-inoculation. These changes in carbohydrate expression
      parallel the infection kinetics, since they appeared first in the vagina and
      later in the uterus. The changes may reflect either a host reaction against the
      infection or the production of enzymes by T. foetus, which act to enhance
      adhesion and colonization of the genital organs by the organism. The kinetics and
      pathogenesis of this murine infection are similar to those of the natural bovine
      disease, suggesting that this model system may be valuable for further studies of
      this disease.

PMID- 18062986
TI  - Becoming a teller of tales: associations between children's fictional narratives
      and parent-child reminiscence narratives.
AB  - Previous research has revealed a connection between the contributions parents
      make while reminiscing and their children's narratives for personally experienced
      events. The current research expands the literature by focusing on the connection
      between parental reminiscing and children's production of fictional narratives.
      After 4- to 9-year-olds and their parents reminisced about past shared events,
      the children (with an experimenter) produced narratives based on wordless picture
      books. The results revealed that the overall quality of the fictional narratives
      was correlated with parents' provision statements that emphasized orientation and
      evaluation in the reminiscence narrative. For younger children, correlations held
      for reminiscence narratives about recent events. For older children, correlations
      held for reminiscence narratives about events from the distant past. The results
      are consistent with the suggestion that children learn general storytelling
      skills from adult models.

PMID- 18062987
TI  - Regulation of carbohydrate metabolism and flight performance by a
      hypertrehalosaemic hormone in the mosquito Anopheles gambiae.
AB  - The role of adipokinetic hormones (AKHs) in the regulation of carbohydrate and
      lipid metabolism and flight performance was evaluated for females of the African
      malaria mosquito, Anopheles gambiae. Injection of various dosages of synthetic
      Anoga-AKH-I increased carbohydrate levels in the haemolymph and reduced glycogen
      reserves in sugar-fed females but did not affect lipid levels. Anoga-AKH-I
      enhanced the flight performance of both intact and decapitated sugar-fed females,
      during a 4 h flight period. Anoga-AKH-II had no effect on carbohydrate or lipid
      levels or flight performance, thus its function remains unknown. Targeted RNA
      interference lowered Anoga-AKH receptor expression in sugar-fed females,
      consequently injections of Anoga-AKH-I failed to mobilize glycogen reserves.
      Taken together, these results show that a primary role for the neurohormone,
      Anoga-AKH-I, is to elevate trehalose levels in the haemolymph of female
      mosquitoes.

PMID- 18062988
TI  - Stimulation of mitochondrial biogenesis and autophagy by lipopolysaccharide in
      the neonatal rat cardiomyocyte protects against programmed cell death.
AB  - Adult rat cardiomyocytes in culture respond to sub-lethal doses of
      lipopolysaccharides (LPS) by activation of pathways including the production of
      TNF-alpha and increased apoptosis. We and others have demonstrated a protective
      phenotype for neonatal rat cardiomyocytes to LPS. Concentrations of LPS far
      exceeding those necessary to induce TNF-alpha release do not induce apoptosis in
      the neonatal cells, although these cells are fully capable or inducing apoptosis
      in response to multiple other stimuli. In neonatal cells, we demonstrate that LPS
      treatment leads to a loss of mitochondrial membrane potential (Deltapsi) which is
      temporally associated with an increase in the level of uncoupling protein 3
      (UCP3). Cells remain viable with no measurable increase in apoptotic or necrotic
      cell death. Many markers of mitochondrial biogenesis are also activated. LPS
      treatment stimulates an increase in the (i) transcription of mitochondrial
      transcription factor A (Tfam), (ii) nuclear accumulation of redox-sensitive
      nuclear respiratory factor 1 (NRF-1), and (iii) expression of peroxisome
      proliferator-activated receptor gamma co-activator 1 (PGC-1). We also observed
      that LPS increased intracellular autophagy. Autophagy was assessed by monitoring
      the levels of a mammalian protein specifically associated with autophagosomes,
      microtubule-associated light chain 3 (LC3). Furthermore, inhibition of autophagy
      in the presence of LPS stimulates markers of apoptosis. Our data suggest that the
      protective response of neonatal cells to LPS is multi-faceted at the level of the
      mitochondrion. Viable cells replace dysfunctional mitochondria by mitochondrial
      biogenesis and the extent of the damage limited by the rapid removal of damaged
      organelles by the stimulation of autophagy.

PMID- 18062990
TI  - Structures of dimeric nonstandard nucleotide triphosphate pyrophosphatase from
      Pyrococcus horikoshii OT3: functional significance of interprotomer
      conformational changes.
AB  - Nonstandard nucleotide triphosphate pyrophosphatase (NTPase) can efficiently
      hydrolyze nonstandard purine nucleotides in the presence of divalent cations. The
      crystal structures of the NTPase from Pyrococcus horikoshii OT3 (PhNTPase) have
      been determined in two unliganded forms and in three liganded forms with inosine
      5'-monophosphate (IMP), ITP and Mn(2+), which visualize the recognition of these
      ligands unambiguously. The overall structure of PhNTPase is similar to that of
      previously reported crystal structures of the NTPase from Methanococcus
      jannaschii and the human ITPase. They share a similar protomer folding with two
      domains and a similar homodimeric quaternary structure. The dimeric interface of
      NTPase is well conserved, and the dimeric state might be important to constitute
      the active site of this enzyme. A conformational analysis of the five snapshots
      of PhNTPase structures using the multiple superposition method reveals that IMP,
      ITP and Mn(2+) bind to the active site without inducing large local
      conformational changes, indicating that a combination of interdomain and
      interprotomer rigid-body shifts mainly describes the conformational change of
      PhNTPase. The interdomain and interprotomer conformations of the ITP liganded
      form are essentially the same as those observed in the unliganded form 1,
      indicating that ITP binding to PhNTPase in solution may follow the selection mode
      in which ITP binds to the subunit that happens to be in the conformation observed
      in the unliganded form 1. In contrast to the human ITPase inducing a large domain
      closure upon ITP binding, the interdomain active site cleft is generally closed
      in PhNTPase and only the IMP binding form shows a remarkable domain opening by 14
      degrees only in the B subunit. The interprotomer rigid-body rotation of PhNTPase
      has a tendency to keep the dimeric 2-fold symmetry, which is also true in human
      ITPase, thereby suggesting its relevance to the positive cooperativity of the
      dimeric NTPases. The exception of this rule is observed in the IMP liganded form
      in which the dimeric 2-fold symmetry is broken by a 3 degrees interprotomer
      rotation in an unusual direction. A combination of the exceptional interdomain
      and interprotomer relocations is most likely the reason for the observed
      asymmetric IMP binding that might be necessary for PhNTPase to release the
      reaction product IMP.

PMID- 18062989
TI  - Structure and orientation of T4 lysozyme bound to the small heat shock protein
      alpha-crystallin.
AB  - We have determined the structural changes that accompany the formation of a
      stable complex between a destabilized mutant of T4 lysozyme (T4L) and the small
      heat shock protein alpha-crystallin. Using pairs of fluorescence or spin label
      probes to fingerprint the T4L tertiary fold, we demonstrate that binding disrupts
      tertiary packing in the two domains as well as across the active-site cleft.
      Furthermore, increased distances between i and i+4 residues of helices support a
      model in which the bound structure is not native-like but significantly unfolded.
      In the confines of the oligomer, T4L has a preferential orientation with residues
      in the more hydrophobic C-terminal domain sequestered in a buried environment,
      while residues in the N-terminal domain are exposed to the aqueous solvent.
      Furthermore, electron paramagnetic resonance spectral line shapes of sites in the
      N-terminal domain are narrower than in the folded, unbound T4L reflecting an
      unstructured backbone and an asymmetric pattern of contacts between T4L and alpha
      crystallin. The net orientation is not affected by the location of the
      destabilizing mutation consistent with the notion that binding is not triggered
      by recognition of localized unfolding. Together, the structural and thermodynamic
      data indicate that the stably bound conformation of T4L is unfolded and support a
      model in which the two modes of substrate binding originate from two discrete
      binding sites on the chaperone.

PMID- 18062991
TI  - The crystal structures of ornithine carbamoyltransferase from Mycobacterium
      tuberculosis and its ternary complex with carbamoyl phosphate and L-norvaline
      reveal the enzyme's catalytic mechanism.
AB  - Mycobacterium tuberculosis ornithine carbamoyltransferase (Mtb OTC) catalyzes the
      sixth step in arginine biosynthesis; it produces citrulline from carbamoyl
      phosphate (CP) and ornithine (ORN). Here, we report the crystal structures of Mtb
      OTC in orthorhombic (form I) and hexagonal (form II) space groups. The molecules
      in form II are complexed with CP and l-norvaline (NVA); the latter is a
      competitive inhibitor of OTC. The asymmetric unit in form I contains a pseudo
      hexamer with 32 point group symmetry. The CP and NVA in form II induce a
      remarkable conformational change in the 80s and the 240s loops with the
      displacement of these loops towards the active site. The displacement of these
      loops is strikingly different from that seen in other OTC structures. In
      addition, the ligands induce a domain closure of 4.4 degrees in form II. Sequence
      comparison of active-site residues of Mtb OTC with several other OTCs of known
      structure reveals that they are virtually identical. The interactions involving
      the active-site residues of Mtb OTC with CP and NVA and a modeling study of ORN
      in the form II structure strongly rule out an earlier proposed mechanistic role
      of Cys264 in catalysis and suggest a possible mechanism for OTC. Our results
      strongly support the view that ORN with an already deprotonated N(epsilon) atom
      is the species that binds to the enzyme and that one of the phosphate oxygen
      atoms of CP is likely to be involved in accepting a proton from the doubly
      protonated N(epsilon) atom of ORN. We have interpreted this deprotonation as part
      of the collapse of the transition state of the reaction.

PMID- 18062993
TI  - Prenatal diet determines susceptibility to cardiac ischaemia-reperfusion injury
      following treatment with diethylmaleic acid and N-acetylcysteine.
AB  - Fetal undernutrition programmes increased risk of developing cardiovascular
      disease in adult life. We hypothesized that prenatal protein restriction would
      impair recovery in post-ischaemic cardiac function in adult offspring through
      antioxidant-mediated processes. Pregnant Wistar rats were fed control or maternal
      low protein diets (MLP) throughout gestation. The offspring of these rats were
      treated with either saline, N-acetylcysteine (NAC), diethylmaleate (DEM), or both
      NAC and DEM to manipulate glutathione status at 6 months of age. Hearts were
      rapidly excised and retro-perfused (Langendorff) to assess isolated cardiac
      function before (baseline), and during 30 min global ischaemia and 60 min
      reperfusion. Hearts from adult rats exposed to a MLP diet in utero suffered
      greater cardiac dysfunction than those from controls following 30 min ischaemia.
      Left ventricular developed pressure (LVDP) was significantly reduced upon early
      reperfusion (p<0.042) in MLP rats compared to controls. NAC pre-treatment had no
      effect on LVDP of hearts from control animal hearts but improved the revival of
      MLP hearts to the same level as controls. DEM treatment did not affect control
      hearts but significantly reduced recovery of LVDP of MLP hearts during early
      (p<0.008) and late reperfusion (0.035). Combined NAC and DEM treatment had no
      effect on LVDP between control and MLP fed offspring. Prenatal protein
      restriction throughout pregnancy increases the susceptibility of the adult rat
      heart to suffer a functional deficit following ischaemia-reperfusion injury.
      Pharmacologically improving antioxidant status prevented this injury. A
      nutritionally-imbalanced developmental environment may increase susceptibility to
      coronary heart disease through the programming of myocardial glutathione
      metabolism.

PMID- 18062992
TI  - Free-living pathogens: life-history constraints and strain competition.
AB  - Many pathogen life histories include a free-living stage, often with anatomical
      and physiological adaptations promoting persistence outside of host tissues. More
      durable particles presumably require that the pathogen metabolize more resources
      per particle. Therefore, we hypothesize functional dependencies, pleiotropic
      constraints, between the rate at which free-living particles decay outside of
      host tissues and other pathogen traits, including virulence, the probability of
      infecting a host upon contact, and pathogen reproduction within host tissues.
      Assuming that pathogen strains compete for hosts preemptively, we find patterns
      in trait dependencies predicting whether or not strain competition favors a
      highly persistent free-living stage.

PMID- 18062994
TI  - Investigating the role of the hypothalamic supraoptic nucleus in nociception in
      the rat.
AB  - We investigated the role of the hypothalamic supraoptic nucleus (SON) in
      nociception in the rat. Electrical stimulation of the SON or microinjection of a
      small dose of L-glutamate sodium into the SON elevated the nociceptive threshold
      in a dose-dependent manner, while cauterization of the SON decreased the
      nociceptive threshold. Pituitary removal did not influence the antinociceptive
      effect of L-glutamate sodium in the SON. The data suggested that the neurons and
      not the nervous fibers in the SON played an important role in antinociception.

PMID- 18062995
TI  - Hydrogen peroxide production in marine bathing waters: Implications for fecal
      indicator bacteria mortality.
AB  - Hydrogen peroxide concentrations [H(2)O(2)] have been measured over the last two
      decades in multiple studies in surface waters in coastal, estuarine and oceanic
      systems. Diurnal cycles consistent with a photochemical production process have
      frequently being observed, with [H(2)O(2)] increasing by two orders of magnitude
      over the course of the day, from low nM levels in the early morning to 10(2)nM in
      late afternoon. Production rates range from <10 for off-shore ocean waters to 20
      60nMh(-1) for near-shore coastal and estuarine environments. Slow night-time loss
      rates (<10nMh(-1)) have been attributed to biological and particle mediated
      processes. Diurnal cycles have also frequently been observed in fecal indicator
      bacteria (FIB) levels in surf zone waters monitored for microbial water quality.
      Measured peak peroxide concentrations in surface coastal seawaters are too low to
      directly cause FIB mortality based on laboratory studies, but likely contribute
      to oxidative stress and diurnal cycling. Peroxide levels in the surf zone may be
      increased by additional peroxide production mechanisms such as deposition,
      sediments and stressed marine biota, further enhancing impacts on FIB in marine
      bathing waters.

PMID- 18062996
TI  - Purification of seawater contaminated with undegradable aromatic ring compounds
      using ozonolysis followed by titanium dioxide treatment.
AB  - Treatment of aromatic ring compounds, 2,4-dichlorophenoxy acetic acid (2,4-D),
      2,4,5-trichloro-phenoxy acetic acid (2,4,5-T), and bisphenol A, in the artificial
      seawater, i.e. Allen seawater, was carried out by ozonation and titanium dioxide
      (TiO2) photocatalyst treatment. Each compound was degraded and varnished within
      30 min by only ozonolysis at pH 9.0 and at 20 degrees C, while the TOC value of
      each compound decreased gradually but reached almost constant value, i.e. about
      70-80% of the initial value, at even 30 min of ozonation time. Ozonolysis (30 min
      of ozonation time) followed by TiO2 photocatalyst treatment (50h of reaction
      time) was a very effective method for decreasing the TOC values of aromatic ring
      compounds in the artificial seawater. In consequence, TOC values of 2,4-D, 2,4,5
      T, and bisphenol A could be reduced to about 28, 21, and 34% of their initial
      values, respectively.

PMID- 18062997
TI  - Trace element concentrations in blood of free-ranging bottlenose dolphins
      (Tursiops truncatus): influence of age, sex and location.

PMID- 18062998
TI  - Trace metals and benthic macrofauna distributions in Camamu Bay, Brazil: sediment
      quality prior oil and gas exploration.

PMID- 18062999
TI  - Model of perfect tandem repeat with random pattern and empirical homogeneity
      testing poly-criteria for latent periodicity revelation in biological sequences.
AB  - A model of perfect tandem repeat with random pattern has been considered. It
      expands a notion of approximate tandem repeat and describes new kind of latent
      periodicity in biological sequences, which has been named profile periodicity.
      Based on this model, an original spectral-statistical approach has been proposed
      for the estimation of size of the periodicity pattern in sequences of approximate
      tandem repeats. In contrast to existing approaches, this is applicable in
      practical conditions of unrepresentative samples (for standard criteria). This
      approach is suitable and effective for preliminary automated revelation of latent
      periodicity. The advantages of the spectral-statistical approach to estimation of
      the periodicity pattern for approximate tandem repeats have been demonstrated in
      comparison with the other methods.

PMID- 18063000
TI  - Modulation of neurotransmitter release by P2X and P2Y receptors in the rat spinal
      cord.
AB  - In this study, the P2 receptor-mediated modulation of [3H]glutamate and
      [3H]noradrenaline release were examined in rat spinal cord slices. Adenosine 5'
      triphosphate (ATP), adenosine 5'-diphosphate (ADP), and 2-methylthioadenosine 5'
      diphosphate (2-MeSADP) decreased the electrical stimulation-evoked [3H]glutamate
      efflux with the following order of potency: ADP>2-MeSADP>ATP. The effect of ATP
      was antagonized by suramin (300microM), the P2Y12,13 receptor antagonist 2
      methylthioadenosine 5'-monophosphate (2-MeSAMP, 10microM), and partly by 4-[[4
      Formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3
      benzenedisulfonic acid (PPADS, 30microM) and the P2Y1 receptor antagonist 2'
      deoxy-N6-methyladenosine 3',5'-diphosphate (MRS 2179, 10muM). ATP, ADP and 2
      MeSADP also decreased evoked [3H]noradrenaline outflow; the order of agonist
      potency was ADP> or =2-MeSADP>ATP. The effect of ATP was reversed by 2-MeSAMP
      (10microM), and partly by MRS 2179 (10microM). By contrast, 2-methylthioadenosine
      5'-triphosphate (2-MeSATP, 10-300microM) increased resting and electrically
      evoked [3H]glutamate and [3H]noradrenaline efflux, and this effect was prevented
      by the P2X1 receptor selective antagonist 4,4',4'',4'''-[carbonylbis[imino-5,1,3
      benzenetriyl bis (carbonyl-imino)]] tetrakis (benzene-1,3-disulfonic acid)
      octasodium salt (NF449, 100nM). Reverse transcriptase polymerase chain reaction
      (RT-PCR) analysis revealed that mRNAs encoding P2Y12 and P2Y13 receptors are
      expressed in the brainstem, whereas P2Y13 but not P2Y12 receptor mRNA is present
      in the dorsal root ganglion and spinal cord. P2Y1 receptor expression in the
      spinal cord is also demonstrated at the protein level. In conclusion, inhibitory
      P2Y and facilitatory P2X1-like receptors, involved in the regulation of glutamate
      (P2Y13 and/or P2Y1) and noradrenaline (P2Y13 and/or P2Y1, P2Y12) release have
      been identified, which provide novel target sites for analgesics acting at the
      spinal cord level.

PMID- 18063002
TI  - Role of DHEA-S on body fat distribution: gender- and depot-specific stimulation
      of adipose tissue lipolysis.
AB  - The objective of this work was to study the possible impact of DHEA-S on body fat
      distribution and the specific action of the hormone on lipolysis from visceral
      and subcutaneous human adipose tissue. First, a clinical evaluation was performed
      in 84 obese patients (29 men, 55 women), measuring serum DHEA-S, computed
      tomography (CT) anthropometric parameters of abdominal fat distribution. In a
      second experiment, subcutaneous and visceral adipose tissue samples were obtained
      from 20 obese patients (10 men, 10 women) and cultured in vitro under stimulation
      with DHEA-S to further assess a possible effect of this hormone on adipose tissue
      lipolysis. Serum DHEA-S was inversely and specifically associated with visceral
      fat area (VA) as assessed by CT in men and with waist-to-hip ratio in women. In
      vitro, DHEA-S increased lipolysis in women's subcutaneous adipose tissue at 2 h,
      while in men, the effect was evident in visceral tissue and after 24 h of
      treatment. In conclusion, DHEA-S contributes to gender-related differences in
      body fat distribution probably by a differential lipolytic action. We have
      demonstrated for the first time in vitro that DHEA-S stimulates lipolysis
      preferably in subcutaneous fat in women and in visceral fat in men.

PMID- 18063001
TI  - Impaired synaptogenesis and long-term modulation of behavior following postnatal
      elevation of GABA levels in mice.
AB  - Antiepileptic drugs acting through the potentiation of GABAergic pathways have
      adverse effects on brain development. Increased risk of impaired intellectual
      development has been reported in children born to women treated for epilepsy
      during pregnancy. We have previously shown, in mice, that treatment with the
      antiepileptic drug vigabatrin (GVG) on postnatal days 4-14 delays reflex
      development in the newborn and impairs learning and memory in the adult. Here, we
      report the time course in which postnatal GVG treatment induced behavioral
      changes in an open field test and had a detrimental developmental effect on
      recognition memory in mice. Furthermore, GVG treatment significantly modulated
      the expression of synaptobrevin/vesicle-associated membrane protein (VAMP) II and
      synaptotagmin (Synt) I. A short-term decrease in the expression of these proteins
      was followed by a long-term elevation in their expression in both the hippocampus
      and the cerebral cortex. In contrast, no changes were detected in the levels of
      Synt II or in the vesicular GABA transporter. The over-expression of VAMP II and
      Synt I in the GVG-treated mice was associated with a significant decrease in the
      basal field excitatory postsynaptic potentials (fEPSP) and modulated the response
      to repeated stimulation. The changes observed in synaptogenesis may explain the
      behavioral impairment induced by postnatal GVG treatment and may suggest a
      possible mechanism for the detrimental effect of antiepileptic drugs acting
      through elevation of GABA levels.

PMID- 18063003
TI  - Understanding mechanisms of toxicity: insights from drug discovery research.
AB  - Toxicology continues to rely heavily on use of animal testing for prediction of
      potential for toxicity in humans. Where mechanisms of toxicity have been
      elucidated, for example endocrine disruption by xenoestrogens binding to the
      estrogen receptor, in vitro assays have been developed as surrogate assays for
      toxicity prediction. This mechanistic information can be combined with other data
      such as exposure levels to inform a risk assessment for the chemical. However,
      there remains a paucity of such mechanistic assays due at least in part to lack
      of methods to determine specific mechanisms of toxicity for many toxicants. A
      means to address this deficiency lies in utilization of a vast repertoire of
      tools developed by the drug discovery industry for interrogating the bioactivity
      of chemicals. This review describes the application of high-throughput screening
      assays as experimental tools for profiling chemicals for potential for toxicity
      and understanding underlying mechanisms. The accessibility of broad panels of
      assays covering an array of protein families permits evaluation of chemicals for
      their ability to directly modulate many potential targets of toxicity. In
      addition, advances in cell-based screening have yielded tools capable of
      reporting the effects of chemicals on numerous critical cell signaling pathways
      and cell health parameters. Novel, more complex cellular systems are being used
      to model mammalian tissues and the consequences of compound treatment. Finally,
      high-throughput technology is being applied to model organism screens to
      understand mechanisms of toxicity. However, a number of formidable challenges to
      these methods remain to be overcome before they are widely applicable.
      Integration of successful approaches will contribute towards building a systems
      approach to toxicology that will provide mechanistic understanding of the effects
      of chemicals on biological systems and aid in rationale risk assessments.

PMID- 18063005
TI  - Differential absorbance study of effects of temperature on chlorine consumption
      and formation of disinfection by-products in chlorinated water.
AB  - Effects of chlorine dose, reaction time and temperature on the formation of
      disinfection by-products (DBPs) and corresponding changes in the absorbance of
      natural organic matter (NOM) in chlorinated water were examined in this study.
      Although variations of chlorination parameters, notably those of temperature that
      was varied from 3 to 35 degrees C, influenced the kinetics of chlorine
      consumption and DBP release, correlations between chlorine consumption,
      concentrations of trihalomethanes (THMs), haloacetonitriles (HANs), other DBP
      species and, on the other hand, intensity of differential absorbance at 272nm
      remained unaffected. THM and HAN speciation was correlated with the differential
      absorbance, indicating preferential incorporation of bromine at the initial
      phases of halogenation that correspond to low DeltaA(272) values. Because the
      DeltaA(272) parameter is a strong indicator of the formation of DBP species and
      chlorine decay, optimization of chlorination operations and DBPs control based on
      this parameter can be beneficial for many water utilities, especially those with
      pronounced variability of water temperature and residence times.

PMID- 18063006
TI  - A general correlation to predict axial dispersion coefficients in aerated channel
      reactors.
AB  - Tracer studies have been widely applied to characterize the flow behavior in
      activated sludge reactors. The channel reactor with bottom aerators is one of the
      widespread designs in large wastewater treatment plants. Its flow behavior is
      well modeled either as a plug flow reactor with axial dispersion or as the
      perfect mixing cells in series. Several correlations have been developed to
      estimate the dispersion coefficients as a function of operating and geometrical
      parameters. These correlations fit properly the data derived from a given reactor
      in the range of operating and geometrical parameters for which they have been
      determined. Unfortunately they cannot be applied straightforwardly with a
      sufficient level of confidence to scale-up industrial units or scale-down
      laboratory pilots. Recently, two papers have proposed more general correlations
      [Makinia, J., Wells, S.A., 2005. Evaluation of empirical formulae for estimation
      of the longitudinal dispersion in activated sludge reactors. Water Res. 39, 1533
      1542; Potier, O., Leclerc, J.-P., Pons, M.-N., 2005. Influence of geometrical and
      operating parameters on the axial dispersion in an aerated channel reactor. Water
      Res. 39, 4454-4462] but they are still not able to represent the whole set of
      data from the literature. This paper proposes a general correlation, which can
      represent all the available and usable sets of data from the literature and more
      than 170 experimental results obtained in our laboratory with a precision of 18%.

PMID- 18063007
TI  - Domestic sampling: exposure assessment to moth repellent products using
      ultrasonic extraction and capillary GC-MS.
AB  - Moth repellent agents are considered major contributors to indoor air pollution.
      In this study, the chemical contamination of clothes due to their direct or
      indirect exposure to moth repellent agents such as p-dichlorobenzene, naphthalene
      and camphor were investigated. Cotton cloths were used as clothing simulant. They
      were analyzed using ultrasonic extraction followed by GC-MS analysis.
      Extrapolated results indicate that a regular cotton shirt indirectly exposed to
      these chemicals in a storage cabinet can contain up to 7, 3 and 7.5mg of p
      dichlorobenzene, naphthalene and camphor, respectively, even after one-hour of
      airing. Passive sorptive sampling using polydimethylsiloxane-coated stir-bars and
      ultrasonic extraction followed by GC-MS analysis was used to monitor the
      concentration distribution in a wardrobe.

PMID- 18063004
TI  - Mechanisms for enveloped virus budding: can some viruses do without an ESCRT?
AB  - Many enveloped viruses complete their replication cycle by forming vesicles that
      bud from the plasma membrane. Some viruses encode "late" (L) domain motifs that
      are able to hijack host proteins involved in the vacuolar protein sorting (VPS)
      pathway, a cellular budding process that gives rise to multivesicular bodies and
      that is topologically equivalent to virus budding. Although many enveloped
      viruses share this mechanism, examples of viruses that require additional viral
      factors and viruses that appear to be independent of the VPS pathway have been
      identified. Alternative mechanisms for virus budding could involve other
      topologically similar process such as cell abscission, which occurs following
      cytokinesis, or virus budding could proceed spontaneously as a result of lipid
      microdomain accumulation of viral proteins. Further examination of novel virus
      host protein interactions and characterization of other enveloped viruses for
      which budding requirements are currently unknown will lead to a better
      understanding of the cellular processes involved in virus assembly and budding.

PMID- 18063008
TI  - Study of the use of coal fly ash as an additive to minimise fluoride leaching
      from FGD gypsum for its disposal.
AB  - The use of coal fly ash as a fluoride retention additive has been studied as a
      way of treating flue gas desulphurisation (FGD) gypsum for its disposal in
      landfills. With this end leaching studies following the standard EN-12457-4
      [Characterization of waste- Leaching-Compliance test for leaching of granular
      waste materials and sludges - Part 4: One stage batch test at a liquid to solid
      ratio of 10l/kg for materials with particle size below 10mm (without or with size
      reduction)] have been performed on FGD gypsum samples treated with different
      proportions of fly ash (0.1-100%). It was found that the fluoride leachable
      content in FGD gypsum was reduced in the range 1-55%, depending on the fly ash
      proportion added to FGD gypsum. High levels of fluoride leaching reduction (close
      to 40%) were achieved even at relatively low fly ash additions (5%). So, low fly
      ash incorporations assure the characterization of this by-product as a waste
      acceptable at landfills for non-hazardous wastes according to the Council
      Decision 2003/33/EC [Council Decision 2003/33/EC of 19 December 2002 establishing
      criteria and procedures for the acceptance of waste at landfills pursuant to
      Article 16 of and Annex II to Directive 1999/31/EC] on waste disposal.
      Furthermore, the effectiveness of the proposed FGD gypsum stabilization method
      was also studied in column leaching systems, proving its good performance in
      simulated conditions of disposal. In such conditions a fluoride leaching
      reduction value slightly higher than 25% was displayed for a fly ash added amount
      of 5%.

PMID- 18063009
TI  - DNA damage response, telomere maintenance and ageing in light of the integrative
      model.
AB  - The complexity of the ageing process is reflected in the fact that numerous
      models have been proposed to explain why and how organisms age and yet they
      address the problem only to a limited extent. A logical solution is to integrate
      individual models together into a wider theoretical framework now known as the
      "network" theory of ageing. The "network" approach overcomes reduction nature of
      individual models and allows for interactions between individual contributing
      mechanisms. This review focuses on some aspects of the "network" approach, namely
      interactions between two individual mechanisms that contribute to ageing: DNA
      damage response and telomere maintenance. The key framework for considering these
      interactions is the previously proposed integrative model, which predicts that
      telomere maintenance is an integral part of DNA damage response machinery. The
      integrative model predicts the dual phenotype, namely dysfunctional DNA damage
      response and dysfunctional telomere maintenance, when one of these mechanisms is
      the cause of ageing. In line with this prediction between 87 and 90% of mouse and
      human models of premature ageing show this dual phenotype. It is concluded that
      the integrative model is consistent with the "network" theory of ageing.

PMID- 18063010
TI  - Lead in the tissues of terrestrial raptors in southern Ontario, Canada, 1995
      2001.
AB  - Terrestrial raptors which feed on upland hunted game species may increase their
      risk to lead exposure and lead poisoning by ingesting lead shot found in the
      tissues of prey. Lead exposure in 225 individuals of nineteen species of
      terrestrial raptors, collected as carcasses in southern Ontario from 1995-2001,
      was examined through the analysis of bone, liver and kidney tissues. In this
      study, one red-tailed hawk contained liver lead concentrations and exhibited
      signs consistent with lead poisoning. Liver and kidney concentrations of one
      turkey vulture were also significantly higher than that associated with
      subclinical effects. This same bird, plus another turkey vulture and a northern
      harrier, had elevated bone lead concentrations (>10 microg/g dw) associated with
      possible toxicity. Turkey vultures had the highest mean concentrations of lead in
      bone and kidney compared to other raptor species. While it appeared only a single
      bird suffered acute lead poisoning, lead levels exceeded threshold concentrations
      associated with subclinical or acute toxicity in 4 of 225, almost 2%, of
      terrestrial raptors assessed. Given the association between lead exposure in
      raptors and hunting of game species reported in other studies, the continued use
      of lead shot for upland hunting in Ontario likely remains as one of the primary
      sources of lead and a continued risk to these birds of prey.

PMID- 18063011
TI  - The use of remote sensing in light use efficiency based models of gross primary
      production: a review of current status and future requirements.
AB  - Global estimation and monitoring of plant photosynthesis (known as Gross Primary
      Production--GPP) is a critical component of climate change research. Modeling of
      carbon cycling requires parameterization of the land surface, which, in a
      spatially continuous mode, is only possible using remote sensing. The increasing
      availability of high spectral resolution satellite observations with global
      coverage and high temporal frequency has allowed the scientific community to
      revisit a number of existing approaches for modeling GPP, and reassess the
      potential for using remotely sensed inputs. In this paper we examine the current
      status and future requirements of modeling global GPP thereby focusing on the
      light use efficiency approach which expresses GPP as product of the
      photosynthetically active radiation (PAR), the fraction of PAR being absorbed by
      the plant canopy (f(PAR)) and the efficiency epsilon with which this absorbed PAR
      can be converted into biomass. The capacity of remote sensing to provide the
      critical input variables for this approach is reviewed and key issues are
      identified and discussed for future research.

PMID- 18063012
TI  - Soil monitoring in Europe: a review of existing systems and requirements for
      harmonisation.
AB  - Official frameworks for soil monitoring exist in most member states of the
      European Union. However, the uniformity of methodologies and the scope of actual
      monitoring are variable between national systems. This review identifies the
      differences between existing systems, and describes options for harmonising soil
      monitoring in the Member States and some neighbouring countries of the European
      Union. The present geographical coverage is uneven between and within countries.
      In general, national and regional networks are much denser in northern and
      eastern regions than in southern Europe. The median coverage in the 50 km x 50 km
      EMEP cells applied all over the European Union, is 300 km(2) for one monitoring
      site. Achieving such minimum density for the European Union would require 4100
      new sites, mainly located in southern countries (Italy, Spain, Greece), parts of
      Poland, Germany, the Baltic countries, Norway, Finland and France. Options are
      discussed for harmonisation of site density, considering various risk area and
      soil quality indicator requirements.

PMID- 18063014
TI  - Measurement of atmospheric PCDD/F and PCB distributions in the vicinity area of
      Waelz plant during different operating stages.
AB  - A comprehensive sampling program was conducted at four sampling sites in the
      vicinity area of a Waelz plant prior to and after the retrofitting of this plant
      for reducing PCDD/F (polychlorinated dibenzo-p-dioxin and polychlorinated
      dibenzofuran) and polychlorinated biphenyl (PCB) emission to evaluate its effects
      on atmospheric PCDD/F and PCB concentrations. During the shutdown stage of the
      Waelz plant investigated, the atmospheric PCDD/F and PCB concentrations measured
      in the vicinity area (sites A, B and C) range from 24 to 170 fg-I-TEQ/m(3) and
      5.0 to 8.2 fg-TEQ(WHO)/m(3), respectively. As the facility restarted to operate,
      the atmospheric PCDD/F and PCB concentrations measured increased to 570-1460 fg-I
      TEQ/m(3) and 23-59 fg-TEQ(WHO)/m(3), respectively. When activated carbon
      injection (ACI) was adopted in the facility in early 2006, the PCDD/F
      concentrations measured in stack gas decreased dramatically from 190 to 3.4 ng-I
      TEQ/Nm(3), while the PCB concentrations decreased from 4.9 to 0.08 ng
      TEQ(WHO)/Nm(3). In the meantime, the atmospheric PCDD/F and PCB concentrations
      measured at sites A, B and C decreased to 150-340 fg-I-TEQ/m(3) and 13-19 fg
      TEQ(WHO)/m(3), respectively. However, relatively high PCDD/F (180-1460 fg-I
      TEQ/m(3)) and PCB (9.3-59 fg-TEQ(WHO)/m(3)) concentrations were measured at site
      D during all sampling stages. Overall, atmospheric sampling results indicate that
      over 50% of PCDD/Fs distributed in solid phase, while over 90% of PCBs
      distributed in vapor phase during all sampling stages.

PMID- 18063013
TI  - Comparative assessment of migrant farm worker health in conventional and organic
      horticultural systems in the United Kingdom.
AB  - This study describes the self-reported health and well-being status of field and
      packhouse workers in UK vegetable horticulture, and tests the null hypothesis
      that there is no difference in the self-reported health of workers on organic and
      conventional horticultural farms. The majority of those sampled were migrant
      workers (93%) from Bulgaria, Latvia, Lithuania, Poland, Russia and the Ukraine.
      More than 95% of the respondents were aged 18-34 and recruited through university
      agricultural faculties in East European or employed via UK agencies. The health
      of 605 farm workers (395 males and 210 females) was measured through the use of
      four standard health instruments. Farm workers' health was significantly poorer
      than published national norms for three different health instruments (Short Form
      36, EuroQol EQ-5D and the Visual Analogue Scale). There were no significant
      differences in the health status of farm workers between conventional and organic
      farms for any of these three instruments. However, organic farm workers scored
      higher on a fourth health instrument the Short Depression Happiness Scale (SDHS)
      indicating that workers on organic farms were happier than their counterparts
      working on conventional farms. Multiple regression analysis suggested that the
      difference in the SDHS score for organic and conventional farms is closely
      related to the range and number of tasks the workers performed each day. These
      findings suggest that a great deal of improvement in the self-reported health of
      farmers will need to occur before organic farms meet the requirements of the
      'Principle of Health' as described by IFOAM. Ensuring that farm workers have a
      varied range of tasks could be a cost effective means of improving self-reported
      health status in both organic and conventional farming systems.

PMID- 18063015
TI  - Mercury in sport fish from the Sacramento-San Joaquin Delta region, California,
      USA.
AB  - Total mercury (Hg) concentrations were determined in fillet tissue of sport fish
      captured in the Sacramento-San Joaquin River Delta and surrounding tributaries, a
      region particularly impacted by historic gold and mercury mining activity. In
      1999 and 2000, mercury concentrations were measured in 767 samples from ten fish
      species. Largemouth bass (Micropterus salmoides), the primary target species,
      exhibited a median Hg concentration of 0.53 mug g(-1) (N=406). Only 23 largemouth
      bass (6%) were below a 0.12 mug g(-1) threshold corresponding to a 4 meals per
      month safe consumption limit. Most of the largemouth bass (222 fish, or 55% of
      the sample) were above a 0.47 mug g(-1) threshold corresponding to a 1 meal per
      month consumption limit. Striped bass (Morone saxatilis), channel catfish
      (Ictalurus punctatus), white catfish (Ameirus catus), and Sacramento pikeminnow
      (Ptychocheilus grandis) also had relatively high concentrations, with 31% or more
      of samples above 0.47 mug g(-1). Concentrations were lowest in redear (Lepomis
      microlophus) and bluegill (Lepomis macrochirus) sunfish, with most samples below
      0.12 mug g(-1), suggesting that targeting these species for sport and subsistence
      fishing may reduce human dietary exposure to Hg in the region. An improved method
      of analysis of covariance was performed to evaluate spatial variation in Hg in
      largemouth bass captured in 2000, while accounting for variability in fish
      length. Using this approach, Hg concentrations were significantly elevated in the
      Feather River, northern Delta, lower Cosumnes River, and San Joaquin River
      regions. In spite of elevated Hg concentrations on all of its tributaries, the
      central Delta had concentrations that were low both in comparison to safe
      consumption guidelines and to other locations.

PMID- 18063016
TI  - Research at Jungfraujoch.
AB  - The High Altitude Research Station at Jungfraujoch is widely recognised as an
      important research site. This is documented by the fact that Jungfraujoch was
      recently selected as one of the 24 Global Atmosphere Watch stations (GAW) within
      the framework of WMO activities. The GAW activities are in line with the
      International Global Observing Strategy (IGOS) on Integrated Global Atmospheric
      Chemistry Observation (IGACO). In addition, Jungfraujoch is an alpine site within
      the Network for the Detection of Atmospheric Composition Change (NDACC).
      Jungfraujoch is also a station within national networks such as the Swiss
      national network of air pollution observation (NABEL), which is part of the
      European Monitoring and Evaluation Program (EMEP), investigating particularly the
      large-scale dissemination of air pollutants within Europe. The station was opened
      in 1931. Therefore, an international conference to celebrate the 75th anniversary
      of the High Altitude Research Station Jungfraujoch was held at Interlaken,
      Switzerland (11-13 September, 2006). Studies across different research fields
      were presented, stimulating discussions among representatives of many disciplines
      from chemists, physicists, astronomers, and biologists to physicians.

PMID- 18063017
TI  - Continuous measurements of aerosol physical parameters at the Mt. Cimone GAW
      Station (2165 m asl, Italy).
AB  - Particle size distribution in the range 0.3<D(p)<or=20 microm, has been analysed
      from August 2002 to July 2006 at the GAW Station of Mt. Cimone (44.10 N, 10.42 E;
      2165 m asl) in the northern Italian Apennines. The seasonal aerosol number size
      distribution, characterized by a bimodal shape, showed a behaviour typical for
      background conditions, characterized by highest values in summer and lowest in
      winter. The seasonal and diurnal variations of the larger accumulation mode
      (0.3<D(p)<or=1 microm average values: 26.15 cm(-3)) and the coarse mode
      (1<Dp<or=20 microm, average value: 0.17 cm(-3)) particle number concentrations (N
      0.3-1 and N 1-20, respectively) exhibited a seasonal cycle with the highest
      values in spring-summer and the lowest value in autumn-winter. Except in winter,
      N 0.3-1 showed a clear diurnal variation with high values during day-time. N 1-20
      showed a less marked diurnal variation (but with higher variability), suggesting
      the influence of non-continuous sources of coarse particle (i.e. Saharan dust
      events). Since July 2005, continuous measurement of black carbon (BC)
      concentrations was also available at the measurement site. On average low BC
      concentrations were recorded (average value: 0.28 microg m(-3)) even if a few
      events of high concentrations were recorded both in warm and cold season. Apart
      from wet scavenging processes which strongly affected aerosol concentrations,
      combined analysis of N 0.3-1, BC, meteorological parameters and air mass back
      trajectories, suggests that the transport of polluted air masses from the lower
      troposphere (by local, regional or long-range transport) represents an important
      mechanism favouring N 0.3-1 and BC increases at Mt. Cimone. In particular, a
      trajectory statistical analysis for the period July 2005-July 2006 allowed the
      identification of the main source regions of BC and N 0.3-1 for Mt. Cimone: north
      Italy, west Europe and east Europe.

PMID- 18063018
TI  - Spatial and temporal changes of chlorinated pesticides, PCBs, dioxins
      (PCDDs/PCDFs) and brominated flame retardants in human breast milk from Northern
      Russia.
AB  - This study presents for the first time temporal changes of organochlorine
      pesticides (OCPs) and polychlorinated biphenyls (PCBs) in Russian human breast
      milk samples. Concentrations of OCPs and PCBs in samples from three locations in
      the North West of Russia in 2000-2002 (n=42), were compared to corresponding
      levels measured in 1993-1996 (n=58). In addition brominated flame retardants
      (BFRs), consisting of polybrominated diphenylethers (PBDEs) (including BDE-209)
      and hexabromocyclododecane (HBCD) were analysed in samples from 2000-2002 (n=37).
      The present levels of SigmaDDTs and SigmaHCHs were 5 and 10 times higher than
      corresponding levels in the neighbouring country Norway. Median concentrations of
      SigmaHCHs (196 microg/kg lw), SigmaCHBs (19.7 microg/kg lw) and SigmaPCBs(16)
      (316 microg/kg lw) were highest in Murmansk. The percentage of p,p'-DDT to
      SigmaDDTs and ratio DDE/DDT suggest possible ongoing use of DDT in Russia. Levels
      of PBDE were low and dominated by the congeners BDE-47 and BDE-153. The deca
      brominated BDE-209 was detected in all analysed samples (median concentration
      0.19 microg/kg lipid). Levels of SigmaOCPs and SigmaPCBs decreased 56 and 30% in
      Murmansk and 36 and 43% in Arkhangelsk during the study period. The decline of
      SigmaOCPs was significant at both locations (p<0.05-p<0.0001). For SigmaPCBs, the
      decreasing trend was only significant in Arkhangelsk (p<0.0001). In addition, a
      decline of Sigmatotal TEQs (SigmaTEQs of PCDDs/PCDFs, non-ortho- and mono-ortho
      PCBs) was observed in Murmansk and Arkhangelsk during the study period. The
      exposure of infants by PCDDs/PCDFs and dioxin-like PCBs is still exceeding the
      daily tolerable intake (TDI) in North West Russia. However, the concentrations of
      PCDDs/PCDFs and dioxin-like PCBs seem to decline very rapidly.

PMID- 18063019
TI  - A global phenomenological model of ischemic stroke with stress on spreading
      depressions.
AB  - In this paper, we establish a new global phenomenological model of ischemic
      stroke. It takes into account local ischemia, energy reduction, propagation of
      spreading depressions (SD), damages to the cells and cellular death by apoptosis
      or necrosis. The spatial diffusion of the ions in the extracellular space which
      triggers the propagation of SD is a central point here. First we expose the
      various biological hypotheses that we have made in this model, and then we
      explain how to determine the parameters and solve the system of equations that we
      obtain. Next we present some results of this model: we simulate a KCl injection
      and then a local ischemia. Finally we discuss results and propose some
      improvements for this model.

PMID- 18063020
TI  - The effect of maximal surgical cytoreduction on sensitivity to platinum-taxane
      chemotherapy and subsequent survival in patients with advanced ovarian cancer.
AB  - OBJECTIVE: In advanced ovarian cancer, patients cytoreduced to no visible disease
      appear to have improved survival compared to patients with visible residual tumor
      < or = 10 mm. It remains unresolved whether this is due to better chemotherapy
      response and/or simply "re-setting the clock," such that patients with less
      residual disease take longer to recur and succumb to their disease. METHODS: We
      reviewed the records of all patients who had primary surgery for stage IIIC-IV
      ovarian cancer at our institution from 1998-2004, followed by intravenous
      platinum-taxane chemotherapy. Primary outcome measures were complete response
      (CR) to initial chemotherapy, platinum resistance at 6 months, progression-free
      (PFS), and overall survival (OS). RESULTS: A total of 296 patients met study
      criteria, of whom 64 (22%) had cytoreduction to no visible disease, 145 (49%) had
      1-10 mm residual disease, and 87 (29%) had > 10 mm residual disease. After
      multivariate analyses, patients cytoreduced to no visible disease demonstrated
      significant improvements in rates of initial complete response and incidence of
      platinum resistance, as well as subsequent improvement in PFS and OS, compared to
      the other two groups. Similarly, patients with 1-10 mm residual disease had
      improved outcomes compared to patients with > 10 mm residual disease for each
      endpoint. CONCLUSIONS: In ovarian cancer patients with < 10 mm residual disease
      who began platinum-taxane therapy, maximal cytoreduction to no visible residual
      disease was associated with improved initial chemotherapy response, less platinum
      resistance, and improved survival. Maximal cytoreduction may improve survival
      through increased sensitivity to initial chemotherapy and should be the goal of
      initial surgery in these patients.

PMID- 18063021
TI  - Expression and activity of taxane-metabolizing enzymes in ovarian tumors.
AB  - OBJECTIVE: Current firstline chemotherapy for ovarian cancer consists of
      carboplatin combined with either paclitaxel or docetaxel. Disposition of
      carboplatin is determined by renal clearance, while the taxanes are metabolized
      by cytochrome P450 (CYP450) enzymes. Although the majority of taxane metabolism
      occurs in the liver, recent data have shown that some solid tumors express CYP450
      enzymes in the tumors themselves. The objective of this study was to determine
      whether ovarian tumors express genes regulating cellular efflux and subsequent
      metabolism, and whether any clinico-pathologic features correlated with
      expression. METHODS: Gene expression of CYP2C8, CYP3A4/A5 and the ABC transporter
      ABCB1 was determined in 56 primary epithelial ovarian tumors. Cells were grown
      from seven different tumors and exposed ex vivo to paclitaxel (PAC) and docetaxel
      (DOC) for up to 24 h. PAC and DOC concentrations were measured in the media by an
      LC-MS assay. RESULTS: Results from this analysis demonstrate that ovarian cancer
      cells do express functional taxane-metabolizing enzymes. Such expression appeared
      to enhance the ability of cancer cells to metabolize DOC. Specifically, the PK of
      DOC was correlated with the ratio of CYP4A5 to ABCB1 gene expression, thus
      representing a novel mechanism of chemotherapy resistance. There was no
      relationship between PAC PK parameters and gene expression. CONCLUSIONS:
      Knowledge of inter-individual variation in CYP450 enzyme and ABC transporter
      tumor expression and activity may influence the individualization of
      chemotherapy, by avoiding agents that are rapidly metabolized and selecting
      agents that are not.

PMID- 18063022
TI  - The role of grammatical class on word recognition.
AB  - The double dissociation between noun and verb processing, well documented in the
      neuropsychological literature, has not been supported in imaging studies. Recent
      imaging studies, in fact, suggest that once confounding with semantics is
      eliminated, grammatical class effects only emerge as a consequence of building
      frames. Here we assess this hypothesis behaviorally in two visual word
      recognition experiments. In Experiment 1, participants made lexical decisions on
      verb targets. We manipulated the grammatical class of the prime words (either
      nouns or verbs and always introduced in a minimal phrasal context, i.e., "the+N"
      or "to+V"), and their semantic similarity to a target (related vs. unrelated). We
      found reliable effects of grammatical class, and no interaction with semantic
      similarity. Experiment 2 further explored this grammatical class effect, using
      verb targets preceded by semantically unrelated verb vs. noun primes. In one
      condition, prime words were presented as bare words; in the other, they were
      presented in the minimal phrasal context used in Experiment 1. Grammatical class
      effects only arose in the latter but not in the former condition thus providing
      evidence that word recognition does not recruit grammatical class information
      unless it is provided to the system.

PMID- 18063023
TI  - Ebolavirus and Marburgvirus: insight the Filoviridae family.
AB  - Ebolavirus and Marburgvirus (belonging to the Filoviridae family) emerged four
      decades ago and cause epidemics of haemorrhagic fever with high case-fatality
      rates. The genome of filoviruses encodes seven proteins. No significant homology
      is observed between filovirus proteins and any known macromolecule. Moreover,
      Marburgvirus and Ebolavirus show significant differences in protein homology. The
      natural maintenance cycle of filoviruses is unknown, the natural reservoir, the
      mode of transmission, the epidemic disease generation, and temporal dynamics are
      unclear. Lastly, Ebolavirus and Marburgvirus are considered as potential
      biological weapons. Vaccine appears the unique therapeutic frontier. Here,
      molecular and clinical aspects of filoviral haemorrhagic fevers are summarized.

PMID- 18063024
TI  - Anxieties in Mainland Chinese and Singapore Chinese adolescents in comparison
      with the American norm.
AB  - There is a growing literature base on child and adolescent anxiety. Cross
      cultural research on child and adolescent anxiety, however, has been relatively
      limited. This study examined whether there were similarities and differences in
      the self reported anxieties in Mainland Chinese and Singapore Chinese adolescents
      (12-17 years of age), and whether these similarities or differences were related
      to gender and/or grade. This study also compared anxiety levels of Mainland
      Chinese and Singapore Chinese adolescents with the American normative sample (12
      17 years of age). The results indicate that the levels of anxieties did not
      differ based on country (China and Singapore). Gender differences were evident.
      Gender and grade interaction effects were found on the anxiety scales. Mixed
      results were found when comparing Mainland Chinese and Singapore Chinese with the
      American normative sample on the different anxiety scales.

PMID- 18063025
TI  - Prevention of cardiovascular disease in high-risk individuals in low-income and
      middle-income countries: health effects and costs.
AB  - In 2005, a global goal of reducing chronic disease death rates by an additional
      2% per year was established. Scaling up coverage of evidence-based interventions
      to prevent cardiovascular disease in high-risk individuals in low-income and
      middle-income countries could play a major part in reaching this goal. We aimed
      to estimate the number of deaths that could be averted and the financial cost of
      scaling up, above current coverage levels, a multidrug regimen for prevention of
      cardiovascular disease (a statin, aspirin, and two blood-pressure-lowering
      medicines) in 23 such countries. Identification of individuals was limited to
      those already accessing health services, and treatment eligibility was based on
      the presence of existing cardiovascular disease or absolute risk of
      cardiovascular disease by use of easily measurable risk factors. Over a 10-year
      period, scaling up this multidrug regimen could avert 17.9 million deaths from
      cardiovascular disease (95% uncertainty interval 7.4 million-25.7 million). 56%
      of deaths averted would be in those younger than 70 years, with more deaths
      averted in women than in men owing to larger absolute numbers of women at older
      ages. The 10-year financial cost would be US$47 billion ($33 billion-$61 billion)
      or an average yearly cost per head of $1.08 ($0.75-1.40), ranging from $0.43 to
      $0.90 across low-income countries and from $0.54 to $2.93 across middle-income
      countries. This package could effectively meet three-quarters of the proposed
      global goal with a moderate increase in health expenditure.

PMID- 18063026
TI  - Prevention of chronic diseases: a call to action.
AB  - Chronic (non-communicable) diseases--principally cardiovascular diseases, cancer,
      chronic respiratory diseases, and diabetes--are leading causes of death and
      disability but are surprisingly neglected elements of the global-health agenda.
      They are underappreciated as development issues and underestimated as diseases
      with profound economic effects. Achievement of the global goal for prevention and
      control of chronic diseases would avert 36 million deaths by 2015 and would have
      major economic benefits. The main challenge for achievement of the global goal is
      to show that it can be reached in a cost-effective manner with existing
      interventions. This series of papers in The Lancet provides evidence that this
      goal is not only possible but also realistic with a small set of interventions
      directed towards whole populations and individuals who are at high risk. The
      total yearly cost of the interventions in 23 low-income and middle-income
      countries is about US$5.8 billion (as of 2005). In this final paper in the Series
      we call for a serious and sustained worldwide effort to prevent and control
      chronic diseases in the context of a general strengthening of health systems.
      Urgent action is needed by WHO, the World Bank, regional banks and development
      agencies, foundations, national governments, civil society, non-governmental
      organisations, the private sector including the pharmaceutical industry, and
      academics. We have established the Chronic Disease Action Group to encourage,
      support, and monitor action on the implementation of evidence-based efforts to
      promote global, regional, and national action to prevent and control chronic
      diseases.

PMID- 18063027
TI  - Chronic disease prevention: health effects and financial costs of strategies to
      reduce salt intake and control tobacco use.
AB  - In 2005, WHO set a global goal to reduce rates of death from chronic (non
      communicable) disease by an additional 2% every year. To this end, we
      investigated how many deaths could potentially be averted over 10 years by
      implementation of selected population-based interventions, and calculated the
      financial costs of their implementation. We selected two interventions: to reduce
      salt intake in the population by 15% and to implement four key elements of the
      WHO Framework Convention on Tobacco Control (FCTC). We used methods from the WHO
      Comparative Risk Assessment project to estimate shifts in the distribution of
      risk factors associated with salt intake and tobacco use, and to model the
      effects on chronic disease mortality for 23 countries that account for 80% of
      chronic disease burden in the developing world. We showed that, over 10 years
      (2006-2015), 13.8 million deaths could be averted by implementation of these
      interventions, at a cost of less than US$0.40 per person per year in low-income
      and lower middle-income countries, and US$0.50-1.00 per person per year in upper
      middle-income countries (as of 2005). These two population-based intervention
      strategies could therefore substantially reduce mortality from chronic diseases,
      and make a major (and affordable) contribution towards achievement of the global
      goal to prevent and control chronic diseases.

PMID- 18063028
TI  - Scaling up interventions for chronic disease prevention: the evidence.
AB  - Interventions to prevent morbidity and mortality from chronic diseases need to be
      cost effective and financially feasible in countries of low or middle income
      before recommendations for their scale-up can be made. We review the cost
      effectiveness estimates on policy interventions (both population-based and
      personal) that are likely to lead to substantial reductions in chronic diseases-
      in particular, cardiovascular disease, diabetes, cancer, and chronic respiratory
      disease. We reviewed data from regions of low, middle, and high income, where
      available, as well as the evidence for making policy interventions where
      available effectiveness or cost-effectiveness data are lacking. The results
      confirm that the cost-effectiveness evidence for tobacco control measures, salt
      reduction, and the use of multidrug regimens for patients with high-risk
      cardiovascular disease strongly supports the feasibility of the scale-up of these
      interventions. Further assessment to determine the best national policies to
      achieve reductions in consumption of saturated and trans fat--chemically
      hydrogenated plant oils--could eventually lead to substantial reductions in
      cardiovascular disease. Finally, we review evidence for policy implementation in
      areas of strong causality or highly probable benefit--eg, changes in personal
      interventions for diabetes reduction, restructuring of health systems, and wider
      policy decisions.

PMID- 18063029
TI  - The burden and costs of chronic diseases in low-income and middle-income
      countries.
AB  - This paper estimates the disease burden and loss of economic output associated
      with chronic diseases-mainly cardiovascular diseases, cancer, chronic respiratory
      diseases, and diabetes-in 23 selected countries which account for around 80% of
      the total burden of chronic disease mortality in developing countries. In these
      23 selected low-income and middle-income countries, chronic diseases were
      responsible for 50% of the total disease burden in 2005. For 15 of the selected
      countries where death registration data are available, the estimated age
      standardised death rates for chronic diseases in 2005 were 54% higher for men and
      86% higher for women than those for men and women in high-income countries. If
      nothing is done to reduce the risk of chronic diseases, an estimated US$84
      billion of economic production will be lost from heart disease, stroke, and
      diabetes alone in these 23 countries between 2006 and 2015. Achievement of a
      global goal for chronic disease prevention and control-an additional 2% yearly
      reduction in chronic disease death rates over the next 10 years-would avert 24
      million deaths in these countries, and would save an estimated $8 billion, which
      is almost 10% of the projected loss in national income over the next 10 years.

PMID- 18063030
TI  - Chronic diseases: the case for urgent global action.

PMID- 18063031
TI  - Structure-activity relationship of a hemagglutinin from Moringa oleifera seeds.
AB  - The hemagglutinin from the seeds of Moringa oleifera (MoL) agglutinates human as
      well as rabbit erythrocytes; the affinity for the latter is almost 250 times more
      than that for the former. MoL was inhibited by glycoproteins namely
      thyroglobulin, fetuin and holotransferin indicating the complex sugar specificity
      of the lectin. The protein is a homodimer with molecular mass of 14kDa, subunits
      (7.1kDa) linked by the disulfide bond(s). The secondary structure elements of MoL
      are alpha-helix, 28%; beta-sheet, 23%; turn 20% and unordered 28%. While the
      activity and secondary structure were not affected at extreme pH and high
      temperature, they were drastically affected in presence of dithiothreitol at and
      above pH 7.0, indicating that disulfide linkages hold the active conformation of
      the protein.

PMID- 18063032
TI  - The changes of serum testosterone level and hepatic microsome enzyme activity of
      crucian carp (Carassius carassius) exposed to a sublethal dosage of
      pentachlorophenol.
AB  - Pentachlorophenol (PCP), which was reported to be a typical persistent organic
      pollutant and environmental endocrine disruptor, may cause threat to aquatic
      species. In this study, serum testosterone concentration, activity of liver
      microsome ethoxyresorufin O-deethylase (EROD) and glutathione S-transferases
      (GST) of crucian carp (Carassius carassius) exposed to PCP for 7 and 15 d,
      respectively, were examined. The results showed that testosterone concentration
      was induced remarkably after 7 d (P<0.05), and the testosterone concentrations in
      15 d treatment crucian carp were higher than those in 7 d treatment. It was found
      that there were significant effects on activities of EROD and GST after crucian
      carp were exposed to PCP for 7 and 15 d (P<0.05), compared to the controls. EROD
      and GST activities increased with increase in PCP concentration and also with
      increase in time on exposure. The results indicated that serum testosterone, EROD
      and GST were sensitive endpoints to PCP. PCP may have endocrine disrupting
      activities and may affect the reproductive success of this species. It is
      possible that the changes of hepatic microsome enzyme activities may result in
      alterations of serum testosterone levels in crucian carp.

PMID- 18063033
TI  - Immediate biomarker responses to benzo[a]pyrene in polluted and unpolluted
      populations of the blue mussel (Mytilus edulis L.) at high-latitudes.
AB  - Immediate biomarker responses of two high-latitude populations of the blue mussel
      Mytilus edulis to benzo[a]pyrene (B[a]P) were evaluated. Mussels collected from a
      clean and a polluted site in southwest Iceland were exposed to the nominal dose
      of 100 microg B[a]P L(-l) for 3 h, after 4 days of acclimatization in clean
      seawater. To test the sensitivity to the toxicant and immediate biological
      responses, the following biomarkers were used: DNA single strand breaks, heart
      rate and feeding rate. All the biomarkers revealed differences between the study
      sites. Irrespective of the origin of the organisms, the short time exposure to
      the high B[a]P concentration did not induce DNA single strand breaks or
      significantly affect the feeding rate. However, the heart rate results showed
      significantly different responses. The mussels from the polluted site (Reykjavik
      harbour) increased their heart rate when exposed to B[a]P, while no difference
      was observed between the heart rate values of the individuals from the clean site
      (Hvassahraun). The mussels seem to sense the pollutant they have been previously
      exposed to, and their acute response indicates physiological adaptation to the
      polluted environment. The results indicate limited sensitivity and temporal
      predictivity, i.e. transient measurable changes of these biomarkers, as well as
      showing that the background of the organisms should be considered when evaluating
      short-term biomarker responses to contaminants.

PMID- 18063034
TI  - Clinical evidence that Asperger's disorder is a mild form of autism.
AB  - OBJECTIVE: The aim of this study is to obtain clinical evidence to test the
      hypothesis that Asperger's disorder (AD) is a mild form of autism (AU). METHOD: A
      78-item Likert scale (the RAADS) was administered to 25 adults with AD and 19
      with AU (ages, 18-65 years) to assess presence, type, and duration of symptoms.
      RESULTS: The following results were found: (a) subjects with AD and AU have
      similar symptoms throughout adulthood (responses to 72 of 78 questions were not
      significantly different); (b) subjects with AD had a significantly fewer total
      number of symptoms; (c) subjects with AD reported nonsignificantly fewer symptoms
      in the DSM-IV-TR domains of social interaction and repetitive patterns of
      behavior; and (d) subjects with AD had significantly fewer symptoms in the
      communication domain. CONCLUSIONS: The data support the hypothesis that AD is a
      mild form of AU, and that they share a common etiology and developmental
      neuropathology. It appears warranted in future diagnostic manuals to incorporate
      AU and AD into 1 diagnostic category such as, "Autism Spectrum Disorder, (with
      modifiers, severe, moderate, mild, atypical, and Asperger's type)."

PMID- 18063035
TI  - Time to emergence of severe suicidal ideation among psychiatric patients as a
      function of suicide attempt history.
AB  - BACKGROUND: Little is known about the emergence of suicidal ideation among
      psychiatric inpatients with histories of no, single, or multiple suicide
      attempts. We investigated differences in time to reemergence of severe suicidal
      ideation among psychiatric patients as a function of their suicide attempt
      histories. METHOD: One hundred seventeen individuals meeting criteria for a major
      depressive disorder who were recently discharged from a psychiatric hospital and
      participating in a larger study of treatments for depression were included in the
      current study. Suicidal ideation, depressive symptoms, hopelessness, and
      depressogenic cognitions were assessed at baseline, and suicidal ideation was
      assessed at 3-, 6-, 12-, and 18-month follow-up, as well as inpatient readmission
      if applicable. Time to the reemergence of severe suicidal ideation was analyzed
      using survival analysis. RESULTS: Twenty-two percent of our sample reported the
      occurrence of severe suicidal ideation over an 18-month period. Severe suicidal
      ideation emerged earlier among patients who had a history of prior suicide
      attempts than those who did not, but single and multiple suicide attempters did
      not differ significantly in time to severe suicidal ideation. Suicide attempt
      history remained a significant predictor of time to severe suicidal ideation when
      statistically controlling for hopelessness, depressive symptoms, depressogenic
      cognitions, and suicidal ideation at admission and initial treatment group
      assignment, especially between single attempters and nonattempters. CONCLUSIONS:
      Although nearly a quarter of participants endorsed severe, clinically significant
      suicidal ideation within 18 months of discharge, those with suicide attempt
      histories reported the occurrence of severe suicidal ideation significantly
      earlier than those without suicide attempt histories.

PMID- 18063036
TI  - Prevalence of suicide ideation, plans, and attempts and related risk factors in
      Italy: results from the European Study on the Epidemiology of Mental Disorders-
      World Mental Health study.
AB  - BACKGROUND: As in other Mediterranean countries, suicide mortality rates in Italy
      are generally lower than they are in Northern and Central European countries and
      on other continents (eg, North America, Australia). Yet, no studies to date have
      examined the prevalence of and risk factors for suicide ideation, plans, and
      attempts, in the general population in Italy. METHODS: Suicide ideation, plans,
      and attempts and potential risk factors were assessed in a community survey
      conducted with 4712 adult respondents (response rate, 71.2%). The participants
      had been selected from Italian municipality resident registries and made up a
      stratified, multistage, clustered probability sample. The project was part of the
      World Health Organization World Mental Health (WMH) Survey Initiative. RESULTS:
      The lifetime prevalence (SE) of suicide ideation, plans, and attempts was 3.0%
      (0.3), 0.7% (0.1), and 0.5% (0.1), respectively. Prevalence rates of these
      suicide-related phenomena did not differ by Italian geographic macro-area
      (Northern, Central, and Southern Italy, including the islands of Sicily and
      Sardinia). Among ideators, the probability of ever making a plan was 24.6% (4.0)
      and attempt was 18.2% (4.5). The probability of making an attempt for ideators
      having made a suicide plan was nearly 50%. Risk factors for lifetime suicide
      related phenomena were female sex, younger cohort, fewer years of education, and
      earlier onset age of suicide ideation. The presence of a common mental disorder,
      especially if comorbid, was associated with a significantly increased risk for
      all suicide phenomena investigated (ideation, plans, and attempts suicide). There
      were no substantial differences in the frequency of these phenomena among the 3
      main macro-areas examined, that is, Northern, Central, and Southern Italy
      (including Sicily and Sardinia), which conversely show marked climate,
      socioeconomic, and cultural differences. CONCLUSION: As shown in previous studies
      examining suicide, suicide continuum phenomena (in terms of ideation, plans, and
      attempt) in Italy were lower than typically observed for other European countries
      and did not differ for different macro-areas presenting remarkably different
      socioeconomic conditions. Prevalence rates of common mental disorders were
      equally lower in Italy than in other European countries. Although the detection
      of mental disorders represents an important step in suicide prevention, the
      correlations observed between various suicidal continuum manifestations suggest
      that timely recognition of suicide ideation and plans is an equally crucial
      factor in the implementation of effective preventive policies.

PMID- 18063037
TI  - Autobiographical memory, interpersonal problem solving, and suicidal behavior in
      adolescent inpatients.
AB  - OBJECTIVE: The aim of the study was to test Williams' (Williams JMG. Depression
      and the specificity of autobiographical memory. In: Rubin D, ed. Remembering Our
      Past: Studies in Autobiographical Memory. London: Cambridge University Press;
      1996:244-267.) theory of suicidal behavior in adolescents and young adults by
      examining the relationship among suicidal behaviors, defective ability to
      retrieve specific autobiographical memories, impaired interpersonal problem
      solving, negative life events, repression, and hopelessness. METHODS: Twenty-five
      suicidal adolescent and young adult inpatients (16.5 y +/- 2.5) were compared
      with 25 nonsuicidal adolescent and young adult inpatients (16.5 y +/- 2.5) and 25
      healthy controls. Autobiographical memory was tested by a word association test;
      problem solving by the means-ends problem solving technique; negative life events
      by the Coddington scale; repression by the Life Style Index; hopelessness by the
      Beck scale; suicidal risk by the Plutchik scale, and suicide attempt by clinical
      history. RESULTS: Impairment in the ability to produce specific autobiographical
      memories, difficulties with interpersonal problem solving, negative life events,
      and repression were all associated with hopelessness and suicidal behavior. There
      were significant correlations among all the variables except for repression and
      negative life events. CONCLUSIONS: These findings support Williams' notion that
      generalized autobiographical memory is associated with deficits in interpersonal
      problem solving, negative life events, hopelessness, and suicidal behavior. The
      finding that defects in autobiographical memory are associated with suicidal
      behavior in adolescents and young adults may lead to improvements in the
      techniques of cognitive behavioral therapy in this age group.

PMID- 18063038
TI  - Course of panic disorder during the early postpartum period: a prospective
      analysis.
AB  - PURPOSE: Most of the studies about course of panic disorder (PD) after childbirth
      have a retrospective nature. The aim of the current study was to examine
      prospectively the clinical course of 13 pregnant women with a diagnosis of PD
      across pregnancy and the early postpartum period. METHOD: The diagnosis of PD was
      determined by means of the Structured Clinical Interview for Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders in the
      third trimester of pregnancy. Within the same period, the Panic and Agoraphobia
      Scale was used to determine the severity of PD. The last assessment with both
      instruments was performed at 6 weeks postnatally. RESULTS: Of these 13 women, 6
      (group 1) reported that PD developed during the 6th to the 28th week of their
      gestation, and the number of women who experienced PD symptoms before pregnancy
      (group 2) was 7. It was found that the severity of panic symptoms considerably
      decreased in the total sample, group 1, and group 2 from the basal levels to 6
      weeks postnatally. CONCLUSION: Our study results suggest that pregnant women with
      PD may experience a marked improvement in PD symptoms in the early postpartum
      period.

PMID- 18063039
TI  - Clinical features associated with treatment-resistant pediatric obsessive
      compulsive disorder.
AB  - OBJECTIVE: The objective of the study was to identify clinical and
      sociodemographic characteristics that may differentiate youth with obsessive
      compulsive disorder (OCD) who are resistant to treatment vs those who have a
      favorable response. METHOD: Participants included 60 outpatients, aged 7-17
      years, who were determined to have previously received an adequate trial of a
      first-line treatment (ie, serotonin reuptake inhibitors, cognitive behavioral
      therapy). Patients who were treatment-resistant were compared with responders on
      a number of factors, including severity and nature of OCD symptoms, levels of
      internalizing and externalizing symptoms, family accommodation of OCD symptoms,
      and functional impairment. RESULTS: The treatment-resistant group endorsed
      significantly more obsessions and compulsions, greater levels of internalizing
      symptoms, higher parental stress related to accommodation, and greater functional
      impairment than treatment responders. However, relative to treatment-resistant
      patients, treatment responders reported higher levels of depressive symptoms,
      perhaps indicating that they were more distressed by their OCD symptoms, as well
      as greater insight into their symptoms. CONCLUSIONS: This study indicates that
      youth with more severe symptoms of OCD, higher related parental stress, and
      greater functional impairment tend to be more resistant to first-line treatments,
      and that perhaps they may require more intensive or family-based interventions.
      Treatment responders report more depressive symptoms and insight into their OCD,
      which may suggest a greater readiness for treatment. Further research likely
      would help to identify which types of treatment would be most beneficial for
      individual youth.

PMID- 18063041
TI  - Uncomplicated and complicated obsessive-compulsive disorder: an exploratory study
      from India.
AB  - Obsessive-compulsive disorder (OCD) is frequently associated with comorbid Axis I
      disorders. Little data are available from the Indian subcontinent. Recent studies
      have raised the possibility of different characteristics of Indian patients with
      OCD. Furthermore, very few studies have compared OCD with comorbid Axis I
      disorders with pure OCD. This cross-sectional exploratory study was carried out
      with the objective of studying Axis I comorbidity in OCD in an Indian setting. It
      also aimed to compare OCD with comorbid Axis I disorder vs pure OCD on multiple
      parameters. Fifty-four patients with OCD (Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition) were included in the present study. Structured
      Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition-I was used to assess Axis I comorbidity. The patients were
      evaluated on different standardized scales measuring obsessive-compulsive,
      anxiety, and depressive symptomatology. Axis I comorbidity was seen in 64.8% of
      the sample. The most common comorbid disorders were depression (38.88%), panic
      disorder (7.40%), and phobias (7.40%). No significant differences were observed
      on sociodemographic variables, but on psychopathological scales, the OCD
      complicated with Axis I disorders subgroup scored higher except in the Yale-Brown
      Obsessive Compulsive Scale compulsion subscale. Frequency and pattern of Axis I
      comorbidity in OCD in an Indian setting are not different from the rest of the
      world. Long-term prospective multicenter epidemiological studies are required to
      understand the development and influence of comorbidity in OCD.

PMID- 18063040
TI  - Correlates of occupational disability in a clinical sample of obsessive
      compulsive disorder.
AB  - OBJECTIVE: This study aimed to examine correlates of occupational disability in a
      large, clinical sample of individuals with a primary diagnosis of obsessive
      compulsive disorder (OCD). METHODS: A total of 238 individuals with a primary
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis
      of OCD were interviewed at entry into an observational study of the course of
      OCD. Primary was defined as the diagnosis that patients identified as the most
      problematic over their lifetime. RESULTS: At the time of interview, 38% of the
      sample reported being unable to work for psychiatric reasons. Obsessive
      compulsive disorder with occupational disability was associated with greater
      functional impairment in completing household duties, social functioning, and
      quality of life. Few differences in treatments received were found among
      individuals with and without occupational disability. Although the number of
      years on psychotropic medications was similar among the 2 groups, those with
      disability had been on a greater number of serotonin-reuptake inhibitors over
      their lifetime. Half of individuals with occupational disability had entered
      cognitive-behavioral therapy at some point, but only one third had received at
      least 13 sessions. Regression analyses revealed that OCD severity was the most
      powerful predictor of occupational disability, followed by depression severity
      and presence of a lifetime substance use disorder. CONCLUSIONS: A substantial
      proportion of individuals in our sample were unable to work. Cognitive-behavioral
      therapy was underutilized, and reasons for this remain unclear. Comorbid
      depression and substance use disorders present additional risk factors for
      disability. Further advances in biologic and psychosocial treatments are needed
      to improve functioning and the overall prognosis of the disorder.

PMID- 18063042
TI  - Coping with posttraumatic stress disorder and comorbidity after myocardial
      infarction.
AB  - OBJECTIVE: Literature on the relationship between coping strategies,
      posttraumatic stress after myocardial infarction (post-MI PTSD), and comorbidity
      is limited. This study aimed to fill this gap in literature by investigating this
      relationship. METHOD: One hundred twenty patients with MI were recruited from 2
      general practices and interviewed using the Posttraumatic Stress Diagnostic
      Scale, the General Health Questionnaire, and the COPE Scale. RESULTS: Thirty-one
      percent had PTSD. Patients used acceptance-focused coping in that most of them
      accepted that the MI had happened and that it could not be changed. At the same
      time, some patients used avoidance-focused coping in that they disengaged
      themselves mentally and behaviorally from the traumatic effects of MI. When the
      variables of age, bypass surgery, mental health problems before MI, and
      angioplasty were held constant, the results showed that patients who used
      maladaptive coping strategies of emotion-focused and avoidance-focused copings
      tended to report more comorbid symptoms. Patients who underwent medical
      procedures or interventions such as bypass surgery and angioplasty tended to
      report more PTSD symptoms. CONCLUSIONS: The way in which MI patients' coping
      strategies relate to health outcomes has been shown to be symptom-specific. Using
      maladaptive coping strategies does not necessarily have a significant impact on
      PTSD symptoms. On the other hand, medical procedures or interventions for
      treating MI can play a major role in maintaining PTSD symptoms for patients with
      MI.

PMID- 18063043
TI  - Hospital use of antipsychotic drugs: polytherapy.
AB  - OBJECTIVE: Growing acceptance of new psychotropic drugs encouraged a survey of
      current use of antipsychotic drugs alone and in combinations, with comparisons
      with previous findings. METHOD: Records from a random sample of McLean Hospital
      (Belmont, Mass) inpatients treated with an antipsychotic from March to May 2004
      were reviewed for Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, discharge diagnosis; all current psychotropic drug treatments; initial,
      peak, and final chlorpromazine-equivalent milligram-per-day dose of
      antipsychotics (APD); initial, peak, and final lithium-equivalent dose (milligram
      per day) of mood stabilizers (MS); weight change; clinical status at admission
      and discharge; and days of hospitalization. RESULTS: In the 305 inpatients
      sampled (n = 184 women, 60.3%), Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, clinical conditions ranked as follows: major affective
      (n = 161, 52.8%), psychotic (n = 99, 32.5%), and other disorders (n = 45, 14.8%).
      Modern drugs comprised 92% of antipsychotic prescriptions, and quetiapine
      (usually at low doses) was most frequently prescribed. "Polytherapy"
      (simultaneous treatment with > or =2 psychotropic agents) at discharge was
      identified in 80% of antipsychotic-treated patients. Use of at least 2
      antipsychotics (in 23% of cases) was associated with a 2.8-fold increase in total
      dose vs monotherapy (651 +/- 403 vs 232 +/- 205 mg/d). Total antipsychotic doses
      also were higher with mood stabilizer (most often divalproex) or sedative
      (usually high-potency benzodiazepine) cotreatment, use of older neuroleptics,
      psychotic-disorder diagnoses, and substance use comorbidity. Polytherapy was not
      associated with superior clinical improvement or shorter hospitalization but was
      associated with higher body weight. CONCLUSIONS: Polytherapy involving
      antipsychotic drugs continues to increase despite limited empirical evidence for
      greater effectiveness or of safety of such combinations.

PMID- 18063044
TI  - Insight in schizophrenia: a review of etiological models and supporting research.

PMID- 18063046
TI  - Causes of schizophrenia reported by urban African American lay community members.
AB  - Although mental health professionals' "etiologic beliefs" concerning
      schizophrenia have evolved in accordance with diathesis-stress and
      neurodevelopmental models, little is known about etiologic attributions in
      nonclinical general population samples in the United States. Yet, course and
      outcome for people with the illness may be indirectly influenced by beliefs about
      causes in the larger community. Because of very limited research in this area,
      especially among African Americans in particular, this descriptive study
      investigated the causes of schizophrenia reported by 127 urban African Americans
      from the general population. The aim of this study was to assess the most
      commonly reported causes of schizophrenia, as well as the frequency of endorsing
      items from a list of 30 factors, some of which are congruent with current
      psychiatric conceptualizations of schizophrenia, whereas others are not. Results
      of this report complement previously reported findings from the same setting
      involving family members of patients with schizophrenia [Esterberg ML, Compton
      MT. Causes of schizophrenia reported by family members of urban African American
      hospitalized patients with schizophrenia. Compr Psychiatry 2006;47:221-226]. The
      5 most commonly reported causes were disturbance of brain biochemistry (49.6%),
      drug/alcohol abuse (42.5%), hereditary factors (40.9%), brain injury (40.2%), and
      avoidance of problems in life (37.8%). The mean number of likely or very likely
      causes endorsed by participants was 7.5 +/- 5.7. Some 47.9% reported one or more
      esoteric factors as a cause. Of the 6 esoteric factors, possession by evil
      spirits (28.3%), radiation (20.2%), and punishment by God (19.7%) were most
      common. Esoteric causes were more commonly chosen by male participants, those
      with 12 years of education or less, and participants who reported never having
      known someone with schizophrenia. Future research should seek to better
      understand how esoteric beliefs about causation affect attitudes toward people
      with mental illnesses and acceptance of mental health treatment by those
      individuals. Beliefs about debunked personality, societal, family, and esoteric
      causes in this nonclinical sample indicate the need for improved psychoeducation
      of the community at large.

PMID- 18063045
TI  - Expanding the schizophrenia phenotype: a composite evaluation of
      neurodevelopmental markers.
AB  - Minor physical anomalies (MPAs) and neurologic soft signs (NSSs) have been
      consistently reported to be more frequent in schizophrenia subjects and their
      first-degree relatives. We aimed at coassessing both these neurodevelopmental
      markers in neuroleptic-naive recent-onset schizophrenia (NRS) subjects in
      comparison to healthy control (HC) subjects to explore the predictive validity of
      this composite endophenotype. We administered the Modified Waldrop Scale (MWS)
      and the Neurological Evaluation Scale (NES) to evaluate MPAs and NSSs,
      respectively, in 40 NRS and 30 matched HC subjects. Schizophrenia subjects had
      significantly higher frequencies of MPAs and NSSs than HC. Minor physical anomaly
      total scores were correlated with greater severity of illness, whereas NES scores
      did not show any relationship with clinical variables. Schizophrenia and HC
      subjects were most accurately classified (82.9%) when MPAs and NSSs were
      considered as a composite phenotype rather than independently. Minor physical
      anomalies and NSSs constitute independent neurodevelopmental markers of
      schizophrenia and would afford greater predictive validity when used as a
      composite endophenotype in genetic association studies.

PMID- 18063047
TI  - Clinical and temperamental differences between early- and late-onset alcoholism
      in Korean men.
AB  - OBJECTIVES: The aims of this study were to elucidate the clinical and
      temperamental differences between early- and late-onset alcoholism among Korean
      men and to ascertain the validity of Cloninger's typology model of alcoholism for
      Koreans. METHODS: All of the subjects were screened after a detoxification period
      of at least 2 weeks using the Structured Clinical Interview for the Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders for
      diagnosing alcohol dependence and identifying psychiatric comorbidities. The
      Korean version of the tridimensional personality questionnaire was then
      administered to 173 male alcoholic inpatients; and information regarding their
      criminality, family history of alcoholism, and age at the onset of alcohol
      related problems was gathered. We divided the patients into 2 groups based on the
      age at the onset of alcoholism: (1) early onset (n = 80), when they were up to 25
      years old at the onset, and (2) late onset (n = 93), when they were older than 25
      years at the onset. RESULTS: Early-onset patients exhibited more criminality
      (chi2 = 15.45, df = 1, P < .001, odds ratio [OR] = 3.84, 95% confidence interval
      [CI] = 1.93-7.65), suicide attempts (chi2 = 7.92, df = 1, P = .005, OR [95% CI] =
      3.14 [1.38-7.15]), and family history of alcoholism (chi2 = 24.75, df = 1, P <
      .001, OR [95% CI] = 5.27 [2.67-10.37]). With regard to the tridimensional
      personality questionnaire profile, the early-onset patients exhibited a higher
      score of novelty seeking (t = 3.42, P = .001), with the difference still being
      significant after adjusting for age by analysis of covariance (using age as a
      covariate) (F = 5.928, P = .016). However, harm avoidance (t = -0.13, P = .89),
      reward dependence (t = -0.19, P = .85), and persistence (t = -0.62, P = .54) did
      not differ between the 2 groups. CONCLUSIONS: There were several distinct
      clinical and temperamental differences between early- and late-onset alcoholism
      among Korean male alcoholic patients. It is suggested that the age at the onset
      of alcoholism can be used to discriminate alcoholic subtypes. Our data also
      partly support Cloninger's typology of 2 types of alcoholic individuals.

PMID- 18063048
TI  - The relationship between the five-factor model and latent Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition personality disorder
      dimensions.
AB  - This study compared the latent structure of the Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Edition personality disorders (PDs) with the 5-factor
      model (FFM) of general personality dimensions. The subjects in the study were 742
      community-residing individuals who participated in the Hopkins Epidemiology of
      Personality Disorders Study. Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition PD traits were assessed by psychologists using the
      International Personality Disorder Examination, and PD dimensions were derived
      previously using dichotomous factor analysis. The Revised NEO Personality
      Inventory, a measure of the FFM, was administered to all subjects. The
      relationship between the 2 sets of personality-related constructs was examined
      using a construct validity framework and also using Pearson correlation
      coefficients, multiple linear regression models, and spline regression models.
      The 5 PD factors each exhibited small to moderate correlations with several NEO
      dimensions; together, the NEO domain and facet scores explained a fifth to a
      third of the variance in PD dimensions. Examples of nonlinear relationships
      between the personality dimensions were identified. There is a modest
      correspondence between the PD dimensions and FFM traits, and the traits of FFM
      only partially explain the variance of the PDs. Dimensional measures of general
      personality may be a suitable alternative to the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition. Whether additional maladaptive traits
      would better define the domain of PDs remains an important objective for future
      research.

PMID- 18063049
TI  - Psychiatrists' knowledge about maternal filicidal thoughts.
AB  - OBJECTIVE: Child murder by mentally ill mothers is an important public health and
      psychiatric concern. However, the authors' clinical and forensic experience has
      been that psychiatrists often do not inquire about maternal thoughts of harming
      their children. This study sought to elucidate the perceptions of psychiatrists
      and psychiatric residents regarding the frequency of such thoughts, and to
      clarify whether they inquire specifically about maternal filicidal thoughts.
      Psychiatrists were expected to underestimate the prevalence maternal thoughts of
      harming their children. It was hypothesized that psychiatrists often do not ask
      their patients about these thoughts. METHODS: This study surveyed psychiatrists
      and psychiatric residents at 2 academic institutions. Respondents were asked
      whether they routinely query women about motherhood, to estimate the frequency of
      thoughts of child harm, and whether they inquire about filicidal thoughts in
      psychotic or suicidal mothers. RESULTS: Two hundred twenty surveys (67%) were
      returned. Most psychiatrists underestimated the frequency of depressed mothers
      who experienced thoughts of harming their young children. Almost one half
      indicated that they do not ask specifically about filicidal ideation but rather
      ask about general homicidal thoughts only. CONCLUSIONS: Psychiatrists should have
      further education about the prevalence of filicidal thoughts and more frequently
      inquire about them.

PMID- 18063050
TI  - Disruption of the C5a receptor gene increases resistance to acute Gram-negative
      bacteremia and endotoxic shock: opposing roles of C3a and C5a.
AB  - The host response to intravascular, Gram-negative bacteria includes profound
      immunologic, hematologic and physiologic changes. Numerous host defense
      mechanisms are activated by Gram-negative bacteria, including the complement
      system. Activation of the complement system leads to cleavage of C5 with
      subsequent generation of the C5a anaphylatoxin peptide. C5a mediates potent,
      proinflammatory activities by binding to the C5a receptor (C5aR, CD88). In this
      study, we report the targeted disruption of the murine C5aR gene (C5aR-/- mice)
      and define the role of the C5aR in a model of Gram-negative bacteremia. Following
      an intravenous infusion of heat-killed Escherichia coli, the C5aR-/- mice were
      completely protected from the mortality suffered by their wild-type littermates
      (P<0.001). The C5aR-/- mice were also significantly (P=0.008) more resistant to
      mortality following an intravenous infusion of purified E. coli endotoxin
      compared to the wild-type littermates. In addition, the C5aR-/- mice were
      resistant to the thrombocytopenia and hemoconcentration observed in wild-type
      animals. Lethality in the wild-type mice was reversed by pre-treatment with
      either the histamine antagonist diphenhydramine or triprolidine. The wild-type
      littermates were also rescued following pre-treatment with the basophil and mast
      cell-stabilizing agent - cromolyn sodium. Collectively, these data demonstrate
      that not only is the absence of the C5aR protective in E. coli bacteremia, but
      that C5aR-dependent histamine release plays a major role in shock induced by Gram
      negative septicemia. Moreover, they provide additional in vivo evidence that C3a
      and C5a have divergent biological functions in Gram-negative bacteremia and
      shock.

PMID- 18063051
TI  - Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid
      (PFOA) causes neurobehavioural defects in adult mice.
AB  - Perfluorinated compounds (PFCs) are found in applications such oil/water
      repellents for clothing fabrics, carpets, food packaging, lubricants, surfactants
      and fire extinguishers. PFCs are persistent in the environment. They have been
      found in humans and in wildlife. We reported earlier that persistent organic
      pollutants (POPs), such as DDT, PCBs and BFRs, caused developmental neurotoxic
      defects in mice, manifested as persistent aberrations in spontaneous behaviour,
      habituation capability, learning and memory, and changes in the cholinergic
      system in adults, when mice were exposed during a critical period of neonatal
      brain development. The present study was conducted to see whether PFCs can cause
      similar developmental neurotoxic effects as earlier observed for POPs as PCBs and
      PBDEs. NMRI male mice were exposed to a single-oral dose, either 1.4 or 21
      micromol/kg body weight of PFOS (0.75 or 11.3 mg), PFOA (0.58 or 8.70 mg), or
      PFDA (0.72 or 10.8 mg), via a metal gastric-tube at the age of 10 days. The
      control animals received in the same manner 10 ml/kg body weight of the 20% fat
      emulsion vehicle. Spontaneous behaviour (locomotion, rearing, and total
      activity), and habituation were observed in 2- and 4-month-old mice. The
      susceptibility of the cholinergic system was explored in a nicotine-induced
      spontaneous behaviour test in 4-month-old mice. Deranged spontaneous behaviour
      was observed in mice exposed to PFOS and PFOA, manifested as reduced and/or lack
      of habituation and hyperactivity in adult mice. These effects were also seen to
      worse with age. Neonatal exposure to PFOS and PFOA affected the cholinergic
      system, manifested as a hypoactive response to nicotine, compared to a
      hyperactive response to nicotine in controls. These developmental neurotoxic
      effects are similar to those we reported earlier for PCBs and PBDEs. This
      suggests that PFOS and PFOA be included in the group of POPs known to be
      developmental neurotoxicants.

PMID- 18063052
TI  - Influence of the anionic ligands on the anticancer activity of Ru(II)-dmso
      complexes: Kinetics of aquation and in vitro cytotoxicity of new dicarboxylate
      compounds in comparison with their chloride precursors.
AB  - We performed extensive studies on the kinetics of hydrolysis of a series of
      Ru(II)-dmso complexes containing dicarboxylate ligands, such as oxalate,
      malonate, succinate and 1,1-cyclobutane dicarboxylate (cbdc), derived from
      anticancer-active Ru(II)-dmso-Cl precursors. The in vitro antitumor activity of
      those compounds in comparison with their chloride precursors was evaluated
      against two tumor cell lines, the human KB oral carcinoma and the murine B16-F10
      melanoma. The aim of this study was to assess how the nature of the anionic
      ligands (i.e. dicarboxylates vs. chlorides) affects the chemical behavior and the
      in vitro antitumor activity of Ru(II)-dmso complexes. Among the tested compounds
      only one complex, the dimer [fac-Ru(dmso-S)(3)(H(2)O)(mu-cbdc)](2) (5), exhibited
      moderate activity against both cell lines. Interestingly, this compound is the
      most kinetically stable in aqueous solution among those investigated. Despite the
      moderate in vitro activity, in an in vivo test, complex 5 exhibited no activity
      against both the primary tumor growth and the formation of spontaneous metastases
      on the MCa mammary carcinoma model.

PMID- 18063053
TI  - Different diagnostic criteria for latent tuberculosis are applied in laboratory
      based research papers.

PMID- 18063054
TI  - Loss of aromatase cytochrome P450 function as a risk factor for Parkinson's
      disease?
AB  - The final step in the physiological synthesis of 17beta estradiol (E(2)) is
      aromatization of precursor testosterone by a CYP19 gene product, cytochrome P450
      estrogen aromatase in the C19 steroid metabolic pathway. Within the central
      nervous system (CNS) the presence, distribution, and activity of aromatase have
      been well characterized. Developmental stage and injury are known modulators of
      brain enzyme activity, where both neurons and glial cells reportedly have the
      capability to synthesize this key estrogenic enzyme. The gonadal steroid E(2) is
      a critical survival, neurotrophic and neuroprotective factor for dopaminergic
      neurons of the substantia nigra pars compacta (SNpc), the cells that degenerate
      in Parkinson's disease (PD). In previous studies we underlined a crucial role for
      the estrogenic status at the time of injury in dictating vulnerability to the
      parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our
      ongoing studies address the contribution of brain aromatase and extragonadal E(2)
      as vulnerability factors for PD pathology in female brain, by exposing aromatase
      knockout (ArKO, -/-) female mice which are unable to synthesize estrogens to
      MPTP. Our initial results indicate that aromatase deficiency from early embryonic
      life significantly impairs the functional integrity of SNpc tyrosine hydroxylase
      positive neurons and dopamine transporter innervation of the caudate-putamen in
      adulthood. In addition, ArKO females exhibited a far greater vulnerability to
      MPTP-induced nigrostriatal damage as compared to their Wt type gonadally intact
      and gonadectomized counterparts. Characterization of this novel implication of
      P450 aromatase as determining factor for PD vulnerability may unravel new avenues
      for the understanding and development of novel therapeutic approaches for
      Parkinson's disease.

PMID- 18063055
TI  - An easy-to-use practical method to measure coincidence in the flow cytometer--the
      case of platelet-granulocyte complex determination.
AB  - Cell complexes composed of two different cells labeled with different
      fluorophores can be detected as double positive events in the flow cytometer.
      Double positivity can originate not only from real complexes but from non
      interacting coinciding cells as well. Coincidence has a high impact on the
      determination of the amount of platelet-granulocyte complexes since platelet
      concentration is in the orders of magnitude higher than that of the granulocytes.
      Mixtures of non-interacting fluorescent beads as well as EDTA anticoagulated or
      citrated blood samples were analyzed in the flow cytometer in the presence and
      absence of fluorescent beads at various dilutions. Experimental data were
      evaluated by mathematical means. The bead or platelet concentration dependence of
      double positivity was converted into linear functions using Poisson distribution.
      This linearised form contains information on the detection volume as well as on
      the presence/absence of dilution independent complexes. The presence of
      appropriate fluorescent beads in the blood sample makes possible to estimate the
      fraction of double positivity originating from coincidence if data collection is
      triggered by the granulocytes or by the fluorescent beads, alternatively. Mixing
      fluorescent beads into a blood sample is a simple experimental method to
      distinguish double positivity originating from real cell-cell complexes from the
      coincidence of cells in a flow cytometer, thus providing a tool for the
      determination of the real amount of cell-cell complexes.

PMID- 18063056
TI  - Presidential address: the illicit use of hormones for enhancement of athletic
      performance: a major threat to the integrity of organized athletic competition.

PMID- 18063057
TI  - Editorial on "The illicit use of hormones for enhancement of athletic
      performance: a major threat to the integrity of organized athletic competition".

PMID- 18063058
TI  - Consequences of parathyroidectomy in patients with "mild" sporadic primary
      hyperparathyroidism.
AB  - BACKGROUND: The use of a targeted, less-invasive approach is changing the
      operative indications in sporadic primary hyperparathyroidism (SPHPT). Now,
      patients with "mild" HPT are offered parathyroidectomy. However, the operative
      findings and outcome of these patients are unknown. This study reports the
      differences between "mild" and "classic" biochemical SPHPT in incidence of
      multiglandular disease (MGD) and operative outcome. METHODS: All 343 patients
      underwent parathyroidectomy guided by intraoperative parathyroid hormone (PTH)
      monitoring (IPM). Among them, 301 patients (88%) had "classic" biochemical SPHPT
      (hypercalcemia and increased PTH) and 42 patients (12%) had "mild" HPT, which
      consisted of 28 patients with inappropriate secretion of PTH (ISP-hypercalcemia
      and normal PTH), and 14 patients with normocalcemic HPT (NCHPT-eucalcemia and
      increased PTH). Single or MGD was determined by IPM. Operative success is
      eucalcemia for greater than or equal to 6 months after operation and along with
      normal PTH levels in NCHPT. RESULTS: Thirty nine of 301 patients (13%) with
      "classic" biochemical SPHPT had MGD with an operative failure rate of 1% (3/301).
      In the "mild" HPT group, 14 of 42 patients (33%) had MGD with a failure rate of
      5% (2/42). The incidence of MGD was statistically significant (P < .001).
      CONCLUSION: The incidence of MGD and operative failure are higher in patients
      with "mild" HPT when compared with classic SPHPT. Patients and surgeons should be
      aware of these consequences when parathyroidectomy is offered to patients with
      "mild" HPT.

PMID- 18063059
TI  - Pheochromocytoma penetrance varies by RET mutation in MEN 2A.
AB  - BACKGROUND: The occurrence of pheochromocytoma in multiple endocrine neoplasia
      type 2A (MEN 2A) carriers varies greatly. This study aims to determine PC
      expression for specific MEN 2A RET mutations. METHODS: Charts of MEN 2A patients
      enrolled in our multiple endocrine neoplasia program from 1990 to 2001 were
      reviewed retrospectively. Statistical analysis was performed using SAS software
      (SAS Institute, Inc, Cary, NC). RESULTS: RET mutation data and pheochromocytoma
      data were compiled for 323 patients. Overall, penetrance of pheochromocytoma
      occurred in 102 of 323 patients (32%). Bilateral pheochromocytomas were observed
      in 67 patients (66%). The following codon-specific expression of pheochromocytoma
      was observed: 1 of 24 patients expressed codon 609 (4%), 0 of 5 patients
      expressed codon 611 (0%), 23 of 105 patients expressed codon 618 (22%), 4 of 45
      patients expressed codon 620 (9%), and 74 of 149 patients expressed codon 634
      (50%) (P < .001). An association between pheochromocytoma expression and amino
      acid substitutions at codon 618 was observed as follows: 0 of 7 patients with
      C618F, 5 of 21 patients with C618G (24%), 11 of 27 patients with C618R (41%), 7
      of 41 patients with C618S (17%), and 0 of 9 patients with C618Y (P = .04.) In our
      cohort, no deaths were attributable to PC with a median follow-up of 9 years.
      CONCLUSIONS: The penetrance of PC varies between MEN 2A RET codon mutations.
      Furthermore, we observed variable expression with different amino acid
      substitutions at the same codon. These results may help guide screening and
      therapy for MEN 2A patients.

PMID- 18063060
TI  - Increased prevalence of breast cancer among patients with thyroid and parathyroid
      disease.
AB  - BACKGROUND: A breast cancer (BC) history was elicited more frequently than
      expected among thyroid operation patients, which prompted an investigation of
      risks for concurrent or subsequent nonendocrine malignancies. METHODS: Of 94,939
      patients at a tertiary referral center with breast, thyroid, or parathyroid
      disease from 2000 to 2006, those patients with more than one tumor type were
      identified. Rates of BC, thyroid cancer (TC), hyperparathyroidism (HPT), and
      multiple diagnoses were compared with matched populations using Surveillance,
      Epidemiology, and End Results (SEER) data. RESULTS: Of those patients identified,
      1604 patients had TC, 12,440 patients had BC, and 1352 patients had HPT. Sixty
      patients with TC (3.7%) and 70 patients with HPT (5.2%) also had BC. Of 820
      consecutive thyroidectomy patients, 23 patients (2.8%) had TC and BC, compared
      with 1.6% expected from a Monte Carlo distribution using SEER data (P = .001). BC
      and TC occurred within 5 years in 90% of patients, who tended to be older than
      those with a single cancer. HPT affected 0.6% of patients with BC, 6% of patients
      with TC, and 7% of patients with both malignancies. CONCLUSION: Patients found
      initially to have TC or BC may be predisposed to develop the other malignancy
      within a short timeframe. HPT is also more prevalent among these patients.
      Vigilant screening for associated disorders should accompany initial diagnosis of
      either cancer.

PMID- 18063061
TI  - Clinical, genetic and radiographic analysis of 108 patients with von Hippel
      Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs).
AB  - BACKGROUND: von Hippel-Lindau (vHL) disease is an autosomal dominant syndrome
      associated with neoplasms in multiple organs, which includes the pancreas. Here,
      we report the greatest single center experience in patients with vHL pancreatic
      endocrine neoplasm (PNETs). METHODS: Between December 1998 and November 2006, 633
      patients with vHL were evaluated and those with PNETs were enrolled on a
      prospective protocol. RESULTS: Overall, 108 vHL patients had PNETs (17%). Nine
      patients had metastatic disease (8.3%) from their PNET. Patients with lesions
      greater than 3 cm (n = 25) were more likely to develop metastases than patients
      with lesions less than 3 cm (n = 83) (P < .005). Thirty-nine patients underwent
      resection. Germline sequencing showed that 78% of patients with metastases (7/9)
      had exon 3 mutations compared with 46% of patients without metastases (32/98; P <
      .01). Tumor doubling time was calculated for the largest PNET. The group with
      metastases had an average tumor doubling time of 337 days (range, 180-463 days)
      compared with 2630 days (range, 103-9614 days) for those without metastases (P <
      .0001). CONCLUSIONS: By implementing a system of selective operative resection
      based on defined criteria, vHL patients with PNETs can be managed safely. For
      patients with small primary lesions (<3 cm), without a mutation of exon 3 and
      slow tumor doubling time (>500 days), a nonoperative approach may be appropriate
      for these nonfunctional neoplasms.

PMID- 18063062
TI  - Long-term follow-up after parathyroidectomy for radiation-induced
      hyperparathyroidism.
AB  - BACKGROUND: External radiation is associated with a risk of hyperparathyroidism.
      We reviewed the outcomes after operation for radiation-induced
      hyperparathyroidism (R-HPT). METHODS: We conducted a retrospective review of all
      patients who had operative therapy for R-HPT from 1980 to 2003 in our department
      with a minimum of 3 years of follow-up after operative therapy. RESULT: Between
      1980 and 2003, 1932 patients underwent parathyroidectomy for primary
      hyperparathyroidism. Thirty-seven (1.92%) patients had a history of neck
      irradiation. Thirty-two patients underwent a bilateral exploration (BE), and 5
      patients had a focused approach (FA). Thirty-five patients presented with single
      gland disease, and 2 patients had multiple gland disease. In the BE group, 26
      patients remained cured biochemically after a median follow-up of 10.3 years
      (range, 3-21 years), and 6 patients had recurrence after a median of 13.2 years
      (range, 7-22 years). In the FA group, all 5 patients remained cured
      biochemically; however, the median follow-up remained shorter (6.4 years; range,
      3-8 years). CONCLUSION: In R-HPT, the incidence of multiple gland disease at the
      time of initial operation was comparable with sporadic HPT. In the absence of
      thyroid disease, an FA may be proposed for R-HPT. Metachronous pathologic glands
      may develop several years after successful parathyroidectomy in R-HPT. Hence,
      lifelong follow-up of these patients is essential.

PMID- 18063063
TI  - Trends in thyroid cancer demographics and surgical therapy in the United States.
AB  - BACKGROUND: The incidence of thyroid cancer is increasing. Our objective was to
      characterize the demographic pattern of this increase and to examine trends in
      surgical therapy for thyroid cancer. METHODS: Analysis of the SEER and NHDS
      databases was performed from 1974 to 2000 and from 1979 to 2004, respectively.
      Thyroid-related diagnoses were extracted, and thyroid cancer (ICD 193.X) were
      analyzed using the SAS statistical package. We compared the population-adjusted
      incidence of thyroid cancer and examined regional variations in the operative
      therapy for thyroid cancer. RESULTS: The incidence of thyroid cancer has
      increased during the past 26 years. This increase occurred predominantly in women
      and in the Northeastern and Southern United States, whereas there has been a
      decrease in thyroid cancers in the Midwest. Papillary cancer accounts for most of
      this increase. Total thyroidectomy (TT) is now the most common operation for
      thyroid cancer. No differences in the use of TT were observed based on hospital
      size or insurance status. CONCLUSION: The increasing incidence of thyroid cancer
      in the United States is predominantly in women. These results suggest that women
      are a high-risk group for developing thyroid cancer although men have higher
      stage disease.

PMID- 18063064
TI  - Pancreatoduodenal surgery in patients with multiple endocrine neoplasia type 1:
      Operative outcomes, long-term function, and quality of life.
AB  - BACKGROUND: Pancreatoduodenal (PD) neoplasms represent the principal disease
      specific lethality in multiple endocrine neoplasia type 1 (MEN1). Potential
      oncologic benefits of PD resection must be weighed against operative morbidities,
      compromised pancreatic function, and quality of life (QOL). METHODS: Fifty MEN1
      patients underwent PD resections during 1984-2004. Postoperative pancreatic
      function and QOL were assessed by EORTC QLQ-C30 and a disease-specific
      questionnaire (response rate, 78%). RESULTS: Twelve patients (24%) had
      asymptomatic disease detected by screening; 38 patients (76%) were symptomatic.
      All gross neoplasm was resected in 80% of patients. No patients died; 21 patients
      (42%) had complications. At 5 years postoperatively, 60% of patients were alive
      without disease, 24% of patients were with disease, 10% of patients died of PD
      neoplasms, 4% of patients died of other malignancies, and 2% of patients died of
      an unknown cause. Diabetes that requires insulin or oral hypoglycemics developed
      in 20% of patients. Frequent steatorrhea (>once/week) occurred in 25% of
      patients, early dumping occurred in 25% of patients, bloating occurred in 25% of
      patients, late dumping occurred in 7% of patients, hypoglycemia occurred in 7% of
      patients, and vomiting occurred in 4% of patients. Global QOL did not differ from
      that of the reference population (72.8 vs 75.3; P = .58). CONCLUSION: PD
      resections in MEN1 are associated with perioperative risks and altered pancreatic
      function. The moderate compromise in patient-perceived QOL suggests that most
      patients accept and adapt to these trade-offs for the potential of prolonged
      survival.

PMID- 18063065
TI  - The incidence of cancer and rate of false-negative cytology in thyroid nodules
      greater than or equal to 4 cm in size.
AB  - BACKGROUND: High false-negative rates for fine needle aspiration biopsy (FNAB) of
      thyroid nodules greater than 3 cm have prompted recommendations for diagnostic
      lobectomy. We considered the presence of a greater than 4 cm nodule an
      independent indication for thyroidectomy regardless of FNAB results. METHODS: We
      reviewed clinical data from 223 patients with thyroid nodules greater than or
      equal to 4 cm operated on from July 2003 to November 2006. Unifocal
      micropapillary cancer was considered clinically insignificant. RESULTS:
      Clinically significant thyroid cancer was frequent, occurring in 57 of 223
      patients (26%). Subgroup analysis showed that 43 of 223 patients (19.3%) had
      carcinoma within the mass and that 7 of 223 patients (3.1%) had significant
      carcinoma elsewhere in the resected thyroid. Multifocal micropapillary cancer was
      found in an additional 7 of 223 patients (3.1%). Preoperative FNAB was read
      incorrectly as benign in 9 of 71 patients with cancer (13%) (16% including
      multifocal micropapillary carcinoma). Benign FNAB results failed to identify 24
      (34%) follicular lesions (including 7 cancers). In patients with preoperative
      FNAB results categorized as indeterminate lesions, 17 of 43 patients (40%) had
      carcinoma of the mass on final pathology. CONCLUSIONS: In thyroid nodules greater
      than or equal to 4 cm, the incidence of carcinoma is high with a high false
      negative rate for preoperative benign cytology. Thyroid nodules greater than or
      equal to 4 cm should be considered for diagnostic lobectomy regardless of FNAB
      results.

PMID- 18063066
TI  - Interpretation of intra-operative PTH changes in patients with multi-glandular
      primary hyperparathyroidism (pHPT).
AB  - BACKGROUND: The correct interpretation of intraoperative parathyroid hormone
      (IOPTH) levels in patients with primary hyperparathyroid patients (pHPT) with
      multiglandular disease (MGD) can impact the success rate of initial parathyroid
      exploration, but it remains an understudied topic. METHODS: In all, 592 of 823
      patients were explored by a single surgeon with biochemical evidence of pHPT
      (1997-2007) and underwent parathyroidectomy using IOPTH. We investigated the
      incidence of MGD in patients with an appreciable (>50%) decrease in IOPTH levels
      and in patients whose levels failed to normalize after single gland excision.
      RESULTS: The mean age of patients was 56.7 years, and 74% of patients were women.
      Thirty-one patients had PTH levels that decreased by greater than 50% from
      baseline 10-15 min after single gland excision, but the levels failed to
      normalize. Of these, 9 patients (29%) had MGD (8 double adenomas, 1 hyperplasia).
      The incidence of MGD in the remainder of IOPTH patients was 13.9% (78 of 561
      patients). Within the subgroup of 31 patients, those with single adenomas did not
      differ from patients with MGD in baseline IOPTH levels and weights of first
      adenoma excised, although they demonstrated greater serum creatinine
      concentrations and a decrease in mean IOPTH. CONCLUSION: Commonly accepted
      decreases in IOPTH levels (>50%) for patients who undergo minimally invasive
      parathyroidectomy may lead to an appreciable number of missed parathyroid
      adenomas or hyperplastic disease.

PMID- 18063067
TI  - Does the presence of additional thyroid nodules on ultrasound alter the risk of
      malignancy in patients with a follicular neoplasm of the thyroid?
AB  - BACKGROUND: Follicular neoplasms of the thyroid are associated with an
      approximately 20% risk of malignancy. We sought to determine whether the presence
      of additional thyroid nodules on preoperative ultrasound decreased the risk of
      malignancy in a patient with a follicular neoplasm. METHODS: Between January 2000
      and November 2006, 325 patients underwent thyroidectomy with a fine needle
      aspiration diagnosis of either follicular neoplasm, Hurthle cell neoplasm, or
      indeterminate (not including suspicious for papillary thyroid cancer). Records
      were reviewed retrospectively and statistical analysis was performed using SPSS
      (SPSS Corporation, Chicago, Ill). RESULTS: The rate of malignancy in our patient
      population was 20% (23% in follicular neoplasm, 19% in Hurthle cell neoplasm, 9%
      in indeterminate). Overall, 57% of patients had multiple thyroid nodules on
      preoperative ultrasound. The risk of malignancy was lower in patients with
      greater than or equal to 1 additional nodule in comparison with those with a
      solitary nodule (16.6% vs 28.0%, P = .02). The risk of malignancy was lowest in
      those with 1-3 additional nodules in comparison with those with greater than or
      equal to 4 nodules (14.5% vs 21.7%, P = .04). CONCLUSIONS: The presence of
      additional thyroid nodules on preoperative ultrasound is associated with a lower
      risk of malignancy in a patient with a follicular neoplasm.

PMID- 18063069
TI  - Routine laryngoscopy in thyroid surgery: A valuable adjunct.

PMID- 18063068
TI  - Laryngoscopy in thyroid surgery--essential standard or unnecessary routine?
AB  - BACKGROUND: Preoperative and postoperative laryngoscopy has been recommended for
      diagnostic and forensic reasons as a standard procedure in all patients who
      undergo thyroid surgery. The aim of this study was to find a more selective
      approach by defining patients at risk of developing vocal fold palsy (VFP).
      METHODS: The history of neck explorations, results of laryngoscopy, and histology
      were registered in all patients who underwent thyroid surgery at our institution
      between 1995 and 1999. Patients with pathologic findings at postoperative
      laryngoscopy underwent reassessment of voice and vocal fold (VF) mobility 6
      months later. RESULTS: Unilateral VFP was detected preoperatively in 13 of 695
      patients (1.9%). Of the 13 patients, only 1 patient was asymptomatic, had no
      history of neck surgery, and had no suspected malignancy. Postoperative
      laryngoscopy revealed a new development of VFP in 68 of 695 patients (9.8%). All
      patients with a permanent VFP had symptoms immediately after operation.
      Asymptomatic VFPs always recovered. CONCLUSIONS: Preoperative laryngoscopy is
      justified in symptomatic patients who undergo reoperation or in patients when
      malignancy is suspected. The necessity of a preoperative laryngoscopy in all
      other patients must be questioned. Postoperative laryngoscopy and additional
      diagnostic testing should be reserved for symptomatic patients.

PMID- 18063070
TI  - Response to mitotane predicts outcome in patients with recurrent adrenal cortical
      carcinoma.
AB  - BACKGROUND: Adrenal cortical carcinoma (ACC) is a rare disease in which
      recurrence after surgery is common. Mitotane is the primary systemic treatment
      for recurrent ACC; data are limited regarding the impact of mitotane on recurrent
      ACC. METHODS: We reviewed the records of all patients who underwent surgery for
      ACC evaluated at our institution from 1991 to 2006. RESULTS: The median disease
      free survival for all 186 patients was 12 months and the median overall survival
      (OS) was 37 months. Higher stage at presentation (P = .002) and tumor cortisol
      production (P = .007) were associated with a worse OS. Mitotane was given to 67
      evaluable patients with recurrent ACC. A response to mitotane was observed in 13
      (19%) of the 67 patients. For patients with stable or responding disease to
      mitotane, the median OS from date of recurrence was 18 months, compared with 9
      months (P = .01) for those who progressed. CONCLUSIONS: Patients with recurrent
      ACC who have stable or responding disease to mitotane have a more favorable
      prognosis than those who progress. Mitotane should be considered in most patients
      with recurrent ACC, including as preoperative therapy for those with recurrent
      disease considered for surgical resection.

PMID- 18063071
TI  - The maturation of a specialty: Workforce projections for endocrine surgery.
AB  - BACKGROUND: There has been an increase in the incidence of endocrine diseases and
      the number of endocrine procedures in the United States. Higher surgeon volume is
      associated with improved patient outcomes. Fellowship programs will lead to more
      specialty-trained endocrine surgeons. We make projections for the supply of
      endocrine surgeons and demand for endocrine procedures over the next 15 years.
      METHODS: Supply projections are based on data from the Accreditation Council for
      Graduate Medical Education, a survey of American Association of Endocrine Surgery
      fellowship program graduates, and Healthcare Cost and Utilization Project
      National Inpatient Sample (HCUP-NIS). Demand is estimated using HCUP-NIS, U.S.
      Census Bureau projections, and a literature review. RESULTS: There were 64,275
      endocrine procedures performed in 2000 and 80,505 in 2004. Using age-adjusted
      population projections and increasing incidence of endocrine diseases, 103,704
      endocrine procedures are anticipated in 2020. High-volume endocrine surgeons are
      few in number, but perform 24% of endocrine procedures. Surgeon supply is
      projected to increase to 938 by 2020; this is based on fellowship graduation
      rates, retirement trends, and increasing annual endocrine case volume among high
      volume surgeons. Alternative projections of supply and demand are generated to
      test the sensitivity of our analyses to different assumptions. CONCLUSION: Labor
      force planning in endocrine surgery is essential if the demand for more high
      volume endocrine specialists is to be met.

PMID- 18063072
TI  - Editorial: the maturation of a specialty: workforce projections for endocrine
      surgery.

PMID- 18063073
TI  - Surgeon volume as a predictor of outcomes in inpatient and outpatient endocrine
      surgery.
AB  - BACKGROUND: Surgeon experience correlates with improved outcomes for complex
      operations. Endocrine operations are increasingly performed in the outpatient
      setting, where outcomes have not been systematically studied. We examined the
      effect of surgeon volume on clinical and economic outcomes for thyroid,
      parathyroid, and adrenal surgery across inpatient and outpatient settings.
      METHODS: New York and Florida state discharge data (2002) were studied. Surgeons
      were grouped by annual endocrine operative volume: Group A, 1 to 3 operations; B,
      4 to 8; C, 9 to 19; D, 20 to 50; E, 51 to 99; and F, >or=100. Multiple regression
      analyses were applied to analyze complications, length of stay (LOS), and total
      charges (TC), while controlling for comorbidity, economic factors, and hospital
      centric variables. RESULTS: We identified 13,997 discharges, with 28% of
      operations performed on an outpatient basis (admission/discharge on same calendar
      day). For all cases, group A contributed disproportionately more complications
      (observed/expected [O/E] 1.65, P < .001) and Group F contributed
      disproportionately less (0.52; P < .001). High surgeon volume was associated with
      decreased LOS and reduced TC. Hospital volume had a negligible effect on
      outcomes. CONCLUSIONS: Surgeon volume correlates inversely with complication
      rates, LOS, and TC, in endocrine surgery. The lowest complication rates are
      achieved by surgeons performing >or=100 endocrine operations annually.

PMID- 18063074
TI  - "Subclinical Cushing's syndrome" is not subclinical: improvement after
      adrenalectomy in 9 patients.
AB  - BACKGROUND: A subgroup of patients with adrenal cortisol hypersecretion fails to
      meet the biochemical criteria for Cushing's syndrome. Appropriate therapy for
      this entity, subclinical Cushing's syndrome (subclinical CS), is unclear. We
      examined outcomes for patients who underwent unilateral adrenalectomy for
      subclinical CS. METHODS: Between 2003 and 2006, all patients who underwent
      adrenalectomy for cortisol hypersecretion caused by an adrenal mass were
      examined. We analyzed biochemical, metabolic, and clinical outcomes. RESULTS:
      Overall, 24 patients underwent adrenalectomy for adrenal cortisol hypersecretion,
      of which 9 were found to have subclinical CS. Median serum cortisol was 2.0
      microg/dL (range, 1.1-6.1) after 1-mg overnight dexamethasone suppression
      testing. Suspicious clinical findings on preoperative examination included skin
      bruising, unexplained weight gain, proximal muscle weakness, abnormal fat pads,
      skin thinning, fatigue, and facial plethora. During a median follow-up period of
      5 months (range, 1-30 months), all 8 patients with easy bruising noted resolution
      postoperatively. Fatigue improved in 4 of 5 patients, muscle weakness in 6 of 8
      patients, and weight in 7 of 9 patients, with a median body mass index change of 
      2.0 kg/m(2) (range, -7.1 to +0.5 kg/m(2)). CONCLUSION: Adrenalectomy improves
      clinical and metabolic parameters for many patients with subclinical CS.

PMID- 18063075
TI  - Utilization of total thyroidectomy for papillary thyroid cancer in the United
      States.
AB  - BACKGROUND: Despite guidelines that recommend total thyroidectomy for papillary
      thyroid cancer (PTC) greater than or equal to 1 cm, the extent of surgery remains
      controversial. We examined surgical practice patterns for PTC greater than or
      equal to 1 cm and identified factors that predict the use of total thyroidectomy.
      METHODS: Of 90,382 patients in the National Cancer Center Data Base (NCDB) with
      PTC from 1985 to 2003, 57,243 patients had tumors greater than or equal to 1 cm
      and underwent total thyroidectomy or lobectomy. Trends in extent of surgery for
      PTC were examined over 2 decades. Logistic regression was used to identify
      factors that predict use of total thyroidectomy compared with lobectomy. RESULTS:
      Use of total thyroidectomy increased from 70.8% in 1985 to 90.4% in 2003 (P <
      .0001). Patients were less likely to undergo total thyroidectomy if they were
      black, older than 45 years, had Medicare, had lower household incomes, or had
      less education (P < .0001). Moreover, patients treated at high-volume or academic
      centers were more likely to undergo total thyroidectomy than were patients
      examined at low-volume or community hospitals (P < .0001). CONCLUSIONS: Use of
      total thyroidectomy for PTC greater than or equal to 1 cm increased over time.
      Differences in use of total thyroidectomy are related to patient, tumor, and
      hospital factors and likely reflect disparities in access to care.

PMID- 18063076
TI  - Increases in parathyroid hormone (PTH) after gastric bypass surgery appear to be
      of a secondary nature.
AB  - INTRODUCTION: Endocrine changes, particularly increases in parathyroid hormone
      (PTH), occurring after gastric bypass procedures have been reported but are not
      well characterized. METHODS: We reviewed retrospectively patients who underwent
      Roux-en-Y (short limb (SL) = 75 cm, long limb (LL) = 165 cm) gastric bypass
      procedures at our institution from January-December 2005. Patient demographics,
      laboratory values of serum calcium, Vitamin D, and phosphorous concentrations as
      well as levels of alkaline phosphate and PTH were followed at quarterly intervals
      for one year. RESULTS: 140 patients were identified. Mean age for the group was
      45 years and 90% of patients were female. The average BMI was 49.2. The mean PTH
      levels increased from 29.4 immediately post-op to 43.1 ng/mL (P < .001) one year
      after surgery. Five percent of the patients had hyperparathyroidism (PTH>53
      ng/mL) immediately postoperatively; the ratio then increased to 21% at one year.
      Only two patients had evidence of true primary hyperparathyroidism with increased
      PTH and hypercalcemia. Sixty percent of patients had at least a 10 ng/mL increase
      in PTH level at the end of one year, reflecting a 30% increase from baseline
      levels. Vitamin D deficiency (levels <20 ng/mL) were identified in 45 patients
      (32%) initially postoperatively and they continued to be low compared to the rest
      of the population (P = .004). Vitamin D levels did vary with seasonal sun
      exposure and were greatest in the third quarter (July-September). Sub-analysis of
      the group showed that patients with LL gastric bypass had lesser Vitamin D
      concentrations (22 vs 30 ng/mL, P < .01) compared to SL patients. CONCLUSION:
      Although preoperative endocrine abnormalities are present in patients undergoing
      gastric bypass procedures, the derangements intensify after gastric bypass
      surgery. A four-fold increase in patients with elevated PTH deserves special
      attention. When combined with the concurrent prevalence of low serum Vitamin D
      and normocalcemia in this population, we propose that this is a disorder of
      secondary hyperparathyroidism requiring medical treatment with Vitamin D
      supplementation.

PMID- 18063077
TI  - Good blood pressure control on antihypertensives, not only response to
      spironolactone, predicts improved outcome after adrenalectomy for aldosteronoma.
AB  - BACKGROUND: Spironolactone is frequently used before adrenalectomy for
      hyperaldosteronism to control blood pressure. Response to spironolactone has been
      suggested to predict a better outcome. However, whether using other
      antihypertensive medications to control blood pressure predicts outcome remains
      unknown. We sought to determine the relationship between preoperative
      normalization of blood pressure with antihypertensive medications and response to
      adrenalectomy for hyperaldosteronism. METHOD: A retrospective cohort study of 102
      patients who underwent adrenalectomy for hyperaldosteronism at a tertiary medical
      center were included. Blood pressures were measured at first clinical
      presentation, preoperatively, postoperatively, and at 1 and 6 months
      postoperatively. The primary outcome measure was complete resolution of
      hypertension (blood pressure <140/90) without antihypertensive medications,
      versus incomplete resolution requiring antihypertensive medications. RESULTS:
      Hypertension resolved and medications were discontinued in 39% of patients.
      Hypertension resolved without medications in 53% of patients who were
      normotensive preoperatively versus 24% of patients who were hypertensive (P =
      .006). In contrast, hypertension resolved without medications in only 45% of
      patients who were normotensive on spironolactone preoperatively versus 34% of
      patients who were hypertensive (P = .38). CONCLUSIONS: Patients with good
      preoperative control of hypertension on antihypertensive medications,
      irrespective of response to spironolactone, are more likely to have complete
      resolution.

PMID- 18063078
TI  - Does histopathology predict parathyroid hypersecretion and influence correctly
      the extent of parathyroidectomy in patients with sporadic primary
      hyperparathyroidism?
AB  - BACKGROUND: Parathyroid histopathology has been used to predict single or
      multiglandular disease (MGD). "Hyperplasia" implies MGD, whereas "adenoma"
      suggests single gland involvement. Intraoperative parathyroid hormone (PTH)
      monitoring (IPM) guides parathyroidectomy based on function. We sought to
      evaluate the accuracy of histopathology in the diagnosis of single or MGD and in
      predicting operative success. METHODS: We reexamined the parathyroid glands from
      402 patients with sporadic primary hyperparathyroidism (SPHPT) who underwent
      initial IPM-guided parathyroidectomies. Operative findings and outcome were
      correlated with histopathology of excised glands. Operative success was
      eucalcemia for >or=6 months and recurrence of hypercalcemia/high PTH after
      successful parathyroidectomy. RESULTS: Of 402 patients, 384 had 1 gland excised
      resulting in operative success; hyperplasia was diagnosed in 244 of the 384
      (64%), with only 2 developing recurrence. Of the 384 patients, 140 (37%) had
      adenomas with 1 late recurrence. There were 18 patients with MGD (14
      hyperplasias, 4 adenomas). There were 5 failures with hyperplasia predicting MGD.
      Histopathology was incorrect in predicting the number of glands involved in 249
      of 402 (62%) patients, and IPM was incorrect in only 13 (3%). CONCLUSION:
      Histopathology of excised abnormal parathyroid glands does not predict the
      secretory function of the remaining parathyroid glands left in situ. IPM guided
      parathyroidectomy accurately based on function alone; however, histopathology was
      inaccurate in predicting MGD and should not be used to guide parathyroidectomy in
      patients with SPHPT.

PMID- 18063079
TI  - Functional parathyroid carcinoma: Long-term treatment outcome and risk factor
      analysis.
AB  - BACKGROUND: This study was conducted to evaluate the long-term outcome of
      surgical treatment in patients with functional parathyroid carcinoma and to
      clarify factors determining prognosis. METHODS: A retrospective review of 38
      patients with parathyroid carcinoma was performed. The Ki-67 index was evaluated
      in 29 cases. Disease-free survival and cause-specific survival estimated using
      the Kaplan-Meier method were analyzed, and the median follow-up period was 119
      months. RESULTS: Fifteen patients developed persistent or recurrent parathyroid
      carcinoma, and 9 patients died of the disease. Twenty-one of 41 reoperations
      normalized the serum calcium level for at least 6 months. Univariate and
      multivariate analyses showed that locoregional tumor extension at initial
      operation and Ki-67 index >or=5% were significant factors affecting cause
      specific survival (P = .0008, P = .05) and disease-free survival (P = .0005, P =
      .005), respectively. Five of 6 patients whose tumor showed a Ki-67 index >or=10%
      developed recurrence within 3 years after initial operation, and 4 died of the
      disease. CONCLUSIONS: Parathyroid carcinomas with locoregional extension at
      initial surgery have potential for recurrence. Our data suggest that aggressive
      surgical resection of recurrent parathyroid carcinoma is beneficial for
      palliation of hypercalcemia in selected patients. Ki-67 staining may be a
      valuable prognostic factor for patients with parathyroid carcinoma, especially as
      tumors with indices greater than 10% are more likely to recur in the early
      postoperative period.

PMID- 18063080
TI  - Report on 8 years of experience with video-assisted thyroidectomy for papillary
      thyroid carcinoma.
AB  - BACKGROUND: The results of video-assisted thyroidectomy in a large series of
      patients with papillary thyroid carcinoma were evaluated, especially in terms of
      the completeness of the operative resection. METHODS: The medical records of all
      patients who underwent video-assisted total thyroid resection (single procedure
      total thyroidectomy or lobectomy followed by completion thyroidectomy) for
      papillary thyroid cancer between June 1998 and December 2006 were reviewed.
      RESULTS: We included 271 patients. One hundred two patients underwent central
      neck node removal by the same approach. Postoperative complications included 5
      patients with transient recurrent nerve palsies, 59 with transient hypocalcemia,
      3 with permanent hypoparathyroidism, and 1 with postoperative hematoma. Final
      histology showed the neoplasms to be 215 pT1, 23 pT2, and 33 pT3. Lymph node
      metastases were found in 19 patients. Follow-up evaluations were completed for
      231 patients. Mean postoperative serum thyroglobulin level after levothyroxine
      withdrawal was 5.5 ng/mL. Postoperative ultrasonography showed no residual
      thyroid tissue in all patients. Mean postoperative (131)I uptake was 2.1%. One
      patient developed a lateral neck recurrence. CONCLUSIONS: The completeness of the
      operative resection achieved with video-assisted thyroidectomy seems comparable
      with that reported for conventional surgery. A longer follow-up is necessary to
      draw definitive conclusions in terms of recurrence and survival rate.

PMID- 18063081
TI  - Therapeutic impact of 18FDG-PET/CT in the management of iodine-negative
      recurrence of differentiated thyroid carcinoma.
AB  - BACKGROUND: 18-F-fluoro-2-deoxyglucose positron emission tomography ((18)FDG-PET)
      is useful in the detection of iodine-negative differentiated thyroid carcinoma
      (DTC). The aim of this prospective study was to assess therapeutic impact of
      (18)FDG-PET imaging using a PET/computed tomography (CT) system in patients with
      iodine-negative recurrence of DTC. METHODS: From 2002 to 2006, patients with
      recurrence of DTC diagnosed by elevated thyroglobulin level and negative 131-I
      whole-body scan were included. RESULTS: Forty-five patients (31 women, 14 men),
      with a mean age of 55 years, with 36 papillary, 5 follicular, and 4 Hurthle
      carcinomas, were studied. All patients had previously undergone total
      thyroidectomy and postoperative thyroid remnant ablation with 131-I. The findings
      of (18)FDG-PET/CT were positive in 31 patients (68.8%) and negative in 14
      (32.2%). Results were true positive in 24 of 31 patients. The sensitivity,
      positive predictive value, and accuracy of (18)FDG-PET/CT were 63%, 77%, and 53%,
      respectively. Twenty patients were operated on, 19 had neck surgery with
      mediastinal lymph node dissection (1 case) and lung resection (1 case), and 1
      underwent lung resection. Seven patients had a stimulated thyroglobulin level <1
      ng/mL. CONCLUSION: (18)FDG-PET/CT is able to select patients who can benefit from
      surgery. Normalization of thyroglobulin is observed in one third of operated
      patients.

PMID- 18063082
TI  - Neuroendocrine tumor cell growth inhibition by ZM336372 through alterations in
      multiple signaling pathways.
AB  - BACKGROUND: We have shown previously that activation of the Raf-1/mitogen
      activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK)1/2
      signaling pathway by ZM336372 inhibits carcinoid cells growth. In the present
      study, we further characterize the molecular details of the growth inhibition by
      the signaling-based compound ZM336372 in neuroendocrine neoplasms (NENs).
      METHODS: NEN cells were treated with ZM336372 (20 to 100 mumol/L) or carrier
      (DMSO). Western Blot was used to determine the activation of the Raf-1/MEK/ERK,
      other pathways activation, and cellular bioactive hormone production. RESULTS:
      ZM336372 in NEN cells resulted in increasing raf-1 activation and inactivation of
      glycogen synthase kinase-3 beta (GSK-3beta) as measured by phosphorylation of
      ERK1/2 and GSK-3beta, respectively. There was no alteration in the levels of
      phosphorylated Akt, an important mediator of the phosphatidyl inositol 3 kinase
      pathway. Importantly, blocking of raf-1 pathway by U0126, a potent inhibitor, in
      the presence of ZM336372 did not reduce the levels of p-GSK-3beta, indicating
      that GSK-3beta inactivation is independent of raf-1 pathway activation. Moreover,
      the levels of chromogranin A and achaete-scute complex like-1 reductions were
      persistent even after blocking the raf-1 pathway. Treatment with ZM336372 in the
      presence of small interfering RNA against raf-1 resulted in an increase in Raf-1
      production, suggesting that ZM336372 upregulates raf-1 at the transcriptional
      level. CONCLUSION: This is the first description of a novel compound ZM336372
      that regulates multiple pathways in NEN cells.

PMID- 18063083
TI  - Same-day ultrasound guidance in reoperation for locally recurrent papillary
      thyroid cancer.
AB  - BACKGROUND: Reoperation for locally recurrent papillary thyroid cancer (PTC) is
      technically difficult and associated with higher morbidity. This study evaluated
      the use of same-day ultrasound guidance (SDUS) as an adjunct. METHODS: We
      compared 2 cohorts of consecutive patients with a single impalpable focus of
      recurrent PTC. Group I (August 2001-January 2004) was explored based on results
      of imaging. Group II (April 2004-January 2007) had an additional SDUS, performed
      before incision with indelible skin marking directly over the lesion. Outcome
      measures included failure to resect, lesion size, and postoperative change in
      thyroglobulin. RESULTS: In group I, in 3 of 6 cases the surgeon was unable to
      find the preoperatively imaged focus. By contrast, all 19 group II patients had
      successful resection of the lesion facilitated by SDUS (P < .01). SDUS resection
      was more likely to succeed even though group II lesions were smaller (mean 17 vs
      11 mm; P = .009). Mean operative times did not differ but morbidity was lower (P
      < .01) in group II. Postresection serum thyroglobulin levels dropped to
      undetectable in 50% of evaluable cases. CONCLUSIONS: When focused resection of
      recurrent PTC is considered appropriate, SDUS guidance is an efficient and useful
      adjunct, allowing resection of lesions as small as 6 mm.

PMID- 18063084
TI  - Same-day ultrasound guidance in reoperations for locally recurrent papillary
      thyroid cancer.

PMID- 18063085
TI  - Treatment of anaplastic thyroid carcinoma in vitro with a mutant vaccinia virus.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a fatal disease resistant to
      all conventional treatments. Novel therapies are needed to improve dismal
      outcomes. METHODS: A replication-competent vaccinia virus (GLV-1h68) was
      engineered by inserting expression cassettes encoding Renilla luciferase-green
      fluorescent protein (GFP), beta-galactosidase, and beta-glucuronidase into the
      genome of LIVP strain. Infection of 6 ATC cell lines by GLV-1h68 was detected in
      vitro at 12, 24, and 36 hours. Viral proliferation was measured through viral
      plaque assays. Cytotoxicity was measured daily at a multiplicity of infection
      (MOI) of 0.01, 0.1 and 1. RESULTS: Viral infection was detected in all cell lines
      by 24 hours and increased in intensity at 36 hours. Logarithmic viral replication
      was detected in all cell lines. At MOI 1, <13% cell survival was measured in 5
      cell lines by day 7. At MOI 0.01, 3 cell lines showed <21% cell survival by day
      7. Luciferase and beta-galactosidase activity at 24 hours correlated with
      cytotoxicity at MOI 0.01 on day 5. CONCLUSION: A replication-competent vaccinia
      virus has significant infectious and oncolytic activity against a panel of human
      ATC. These results encourage future in vivo and clinical studies for this novel
      agent to treat this fatal cancer.

PMID- 18063086
TI  - Parafibromin expression, single-gland involvement, and limited parathyroidectomy
      in familial isolated hyperparathyroidism.
AB  - BACKGROUND: Familial isolated hyperparathyroidism (FIHPT) is a rare syndrome
      linked to HRPT2 mutations, with a variable extent of parathyroid involvement.
      Extensive parathyroidectomy is usually indicated, but single-gland involvement is
      often reported. Recently, loss of parafibromin expression (caused by HRPT2
      inactivating mutations) has been suggested as a distinguishing feature of FIHPT.
      This study aimed to evaluate the extent of parathyroid involvement and
      parafibromin expression in FIHPT. METHODS: Twelve patients from 3 FIHPT families
      underwent bilateral neck exploration, selective excision of macroscopically
      enlarged parathyroids, and biopsy of the remaining glands. Parafibromin
      expression was evaluated and compared with that in normal parathyroids and in
      adenomas arising in sporadic hyperparathyroidism. RESULTS: Pathology confirmed
      single-gland involvement in all cases (11 adenomas and 1 carcinoma). Limited
      parathyroidectomy achieved a cure in 91.6% (1 persistent case of parathyroid
      carcinoma). After a mean follow-up of 9.4 years, all remaining patients are
      disease free, although 3 underwent successful reoperation for single-gland long
      term recurrence. Parafibromin expression was absent in all macroscopically
      affected glands from FIHPT patients, but present in normal parathyroids and in
      adenomas arising in sporadic hyperparathyroidism. CONCLUSIONS: Loss of
      parafibromin expression is a distinguishing marker of parathyroid involvement in
      FIHPT. Single-gland involvement often occurs; limited parathyroidectomy is
      effective and achieves long disease-free periods.

PMID- 18063087
TI  - The preoperative exclusion of thyroid carcinoma in multinodular goiter: Dynamic
      contrast-enhanced magnetic resonance imaging versus ultrasonography-guided fine
      needle aspiration biopsy.
AB  - BACKGROUND: We compared the diagnostic values of dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) and ultrasonography (USG)-guided fine-needle
      aspiration biopsy (FNAB) in the detection of thyroid carcinoma associated with
      multinodular goiter. METHODS: USG-guided FNAB and DCE-MRI were performed
      consecutively on 26 patients who had multinodular goiter with dominant nodules
      and clinical suspicion of malignancy. DCE-MRI findings, cytodiagnosis, and final
      histopathologic results were correlated. We compared the sensitivity,
      specificity, diagnostic accuracy, and positive (PPV) and negative predictive
      values (NPV) of DCE-MRI and USG-guided FNAB. RESULTS: Of 57 nodules in 26
      patients, 16, 37, and 4 nodules showed delayed, plateau, and rapid washout
      patterns, respectively. Thyroid carcinoma was found in 8 patients (31%). Delayed
      washout pattern in a nodule was correlated with the histologic diagnosis of
      thyroid carcinoma (P < .001). None of the nodules with thyroid carcinoma had a
      plateau or rapid washout pattern. The sensitivity and NPV of DCE-MRI to diagnose
      thyroid carcinoma were greater when compared with those in USG-guided FNAB (100
      vs 71.4%, and 100 vs 91.7%, respectively; P < .001). CONCLUSION: When other
      diagnostic methods are inconclusive, DCE-MRI is superior to USG-guided FNAB to
      exclude thyroid carcinoma in patients with multinodular goiter.

PMID- 18063088
TI  - Medullary thyroid microcarcinoma recommendations for treatment - a single-center
      experience.
AB  - BACKGROUND: Conflicting recommendations exist regarding lymph node (LN) surgery
      in microMTC (<or=10mm). This study aims to correlate biochemical and
      pathohistological findings in an attempt to define the characteristics of
      microMTC, thus allowing recommendations for LN surgery. METHODS: Patients with
      elevated basal (bCT:>or=10pg/ml) and pentagastrin-stimulated calcitonin levels
      (sCT:>100pg/ml) were selected for initial surgery. None of the patient was a
      member of any known MTC family. Biochemical and morphological data of microMTC
      were compared with 146 patients with C-cell hyperplasia (CCH). RESULTS: MicroMTC
      (tumor diameter: 4.2+/-2.6mm; unifocal:68; multifocal:29) was documented in 97 of
      159 (61%) MTC patients. In 11 (11%) patients, 1-19 LNs were involved. Correlating
      bCT and sCT levels neither predicted N-stage, nor differentiated between microMTC
      and CCH. CONCLUSIONS: The biochemical discrimination cannot be made between
      patients with CCH and MTC, and patients with MTC with/without LN metastasis.
      Thus, thyroidectomy and central neck dissection is indicated in patients with
      "mildly" elevated sCT levels (<560pg/ml) (LN positive: 1 of 37 patients [2.7%]).
      A lateral neck dissection may be added "on demand" (in the setting of measurable
      postoperative bCT and/or sCT levels indicating LN metastasis). Patients with
      "highly" elevated sCT (>or=560pg/ml) must be treated as "palpable" MTC (LN
      positive: 10 of 54 patients [18.5%]).

PMID- 18063089
TI  - Trends in adrenalectomy rates, indications, and physician volume: A statewide
      analysis of 1816 adrenalectomies.
AB  - BACKGROUND: Adrenalectomy rates seem to be increasing in Florida, possibly due to
      increased availability of laparoscopic adrenalectomy, identification of
      incidentalomas, and access to care for minorities. We hypothesized that the rate
      of adrenalectomies in Florida increased from 1998-2005 while characteristics of
      patients, diagnoses, operations, and operating physicians changed over this
      period. METHODS: Prospectively-collected, mandatory-reported, hospital discharge
      data for all inpatient adrenalectomies undertaken in Florida from 1998-2005 were
      obtained along with Florida census and physician certification and education
      data. Characteristics of adrenalectomy patients, diagnoses, operations, and
      physicians were analyzed. RESULTS: 1816 adrenalectomies were available for
      analysis. Yearly rates of adrenalectomy nearly doubled from 1.20 to 2.26 per
      100,000 Florida residents (P = .0024). Overall, patient characteristics such as
      demographics, indications and comorbidities did not change, whereas hospital
      charges increased and length-of-stay (LOS) significantly decreased (P = .0031 and
      P < .0001, respectively). There was a non-significant trend toward a yearly
      increase in physician volume and an inverse relationship between physician volume
      categories and mean LOS (P < .0001). CONCLUSIONS: The rate of adrenalectomies is
      increasing in Florida. This increase was not associated with distinct trends in
      patient characteristics, although a significant decrease in LOS was identified.
      As these trends continue and adrenalectomy is applied more liberally, indications
      for adrenalectomy may need to be re-evaluated.

PMID- 18063091
TI  - Impact of 25 hydroxyvitamin D deficiency in perioperative parathyroid hormone
      kinetics and results in patients with primary hyperparathyroidism.

PMID- 18063090
TI  - Impact of 25-hydroxyvitamin D deficiency on perioperative parathyroid hormone
      kinetics and results in patients with primary hyperparathyroidism.
AB  - BACKGROUND: Successful parathyroidectomy for sporadic primary hyperparathyroidism
      (pHPT) is predicted by a 50% drop in PTH intra-operatively. Vitamin D is a known
      inhibitor of PTH secretion and is associated with secondary HPT following adenoma
      resection. This study examined the impact of 25-hydroxyvitamin D (25OHD)
      deficiency on perioperative PTH kinetics and outcomes following
      parathyroidectomy. METHODS: Patients undergoing adenoma resection for pHPT (n=93)
      had PTH levels recorded at six perioperative time points. Preoperative 25OHD
      levels were examined retrospectively. Patients were considered 25OHD deficient if
      the level was <25 ng/mL (n=47) and adequate if the level was >or=25 ng/mL (n=46).
      RESULTS: Patients with 25OHD-deficiency had significantly higher preoperative
      calcium, alkaline phosphatase, and PTH levels. PTH levels were significantly
      higher in 25OHD-deficient patients at incision, at 1 week postop and 1-3 months
      postop. Average drop in PTH level five minutes post resection was 79+/-14% in the
      deficient group and 72+/-22% in the non-deficient group (P=.03). 25OHD levels
      inversely correlated with adenoma weight (P=.03) and postoperative PTH
      measurements (P=.008). CONCLUSIONS: Sporadic pHPT patients with 25OHD deficiency
      have higher baseline and postoperative PTH levels compared to non-deficient
      patients but do not have altered intraoperative PTH kinetics. Vitamin D
      deficiency is associated with postoperative elevation of PTH.

PMID- 18063092
TI  - NMDA-induced striatal brain damage and time-dependence reliability of thionin
      staining in rats.
AB  - Excitotoxic neuronal death induced by intracerebral injection of NMDA is a widely
      used model for investigating the potentially neuroprotective action of
      pharmacological agents against brain insults involving excitotoxic processes.
      Surprisingly, the time-course of NMDA-induced brain damage yet has not been
      investigated in the rat. Answering this question clearly needs to be assessed,
      given that the validity of preclinical neuroprotection studies requires to be
      insured that brain damage has reached a plateau that corresponds to the maximal
      extension of neuronal death at the time the brain is removed for histological
      analysis. Here, we investigated the time-course of neuronal death and the time
      dependence validity of thionin coloration in rats that were given an
      intrastriatal injection of NMDA of 50 nmol or 70 nmol. Our results show that,
      whatever the dose used, NMDA-induced brain damage reaches its maximal value 24-48
      h after the insult. They further indicate that the volume values of brain damage
      as estimated by thionin coloration constitute reliable data when the brain is
      removed up to 48 h after injection of NMDA. However, if the brain is removed more
      than 48 h after the excitotoxic insult onset, there is no alternative of using
      other techniques, such as immunochemical or neuroimaging techniques.

PMID- 18063093
TI  - Insulin resistance and depressive symptoms in middle-aged and elderly Chinese:
      findings from the Nutrition and Health of Aging Population in China Study.
AB  - BACKGROUND: Depression is associated with an increased risk of incident diabetes,
      and insulin resistance is thought to be the underlying link between them.
      Nevertheless, only a few studies have explored the association between insulin
      resistance and depression with contradictory results, and none have been
      conducted in Chinese populations. METHODS: We aimed to determine the association
      between insulin resistance and depressive symptoms among middle-aged and elderly
      Chinese using data from the Nutrition and Health of Aging Population in China
      Study, a population-based cross-sectional study conducted in 2005 in China.
      Participants included 3285 community residents aged 50-70 years. Depressive
      symptoms were defined as a Center for Epidemiological Studies of Depression Scale
      (CES-D) score of 16 or higher. Insulin resistance was calculated using the
      updated homeostasis model assessment (HOMA2-IR) methods. RESULTS: Value of HOMA2
      IR was significantly higher in participants with depressive symptoms (0.284 vs.
      0.261, P=0.008), even after adjustment for various confounding factors in the
      regression model (0.311 vs. 0.291, P=0.026). Logistical regression analyses
      showed that participants with depressive symptoms had a higher risk of having
      insulin resistance (defined as in the top quartile of HOMA2-IR values, odds
      ratio=1.54, 95% confidence intervals=1.17-2.04). LIMITATIONS: Due to the cross
      sectional study design, causal relation remains unknown. CONCLUSIONS: The present
      study found positive associations between depressive symptoms and insulin
      resistance among Chinese populations. Further prospective studies are needed to
      validate the results and find the temporal and causal relation between them.

PMID- 18063095
TI  - ABO blood group phenotypes and Plasmodium falciparum malaria: unlocking a pivotal
      mechanism.
AB  - Host susceptibility to Plasmodium falciparum infection is central for improved
      understanding of malaria in human populations. Red blood cell (RBC) polymorphisms
      have been proposed as factors associated with malaria infection or its severity,
      although no systematic appraisal of ABO phenotypes and malaria risk has been
      undertaken. This analysis summarises epidemiological, clinical and immunological
      evidence on the nature of ABO histo-blood antigens and their interaction with
      malaria in terms of population genetics, infection risk, severe malaria and
      placental malaria. In non-pregnant subjects, a meta-analysis showed no conclusive
      evidence associating ABO phenotypes with risk of uncomplicated malaria. There was
      stronger evidence that ABO phenotype modulates severity of P. falciparum malaria,
      with group A associated with severe disease and blood group O with milder
      disease. Among pregnant subjects, group O was associated with increased risk of
      placental malaria in primigravidae and reduced risk in multigravidae. The
      biological basis for ABO-related susceptibility to malaria is reviewed. Several
      mechanisms relate to these associations including affinity for Anopheles gambiae;
      shared ABO antigens with P. falciparum; impairment of merozoite penetration of
      RBCs; and cytoadherence, endothelial activation and rosetting. ABO phenotypic
      associations with malaria are related to its pathogenesis and improved
      understanding of these interactions is required for understanding the
      glycobiology of malaria infection.

PMID- 18063096
TI  - Structure and content of the Entamoeba histolytica genome.
AB  - The intestinal parasite Entamoeba histolytica is one of the first protists for
      which a draft genome sequence has been published. Although the genome is still
      incomplete, it is unlikely that many genes are missing from the list of those
      already identified. In this chapter we summarise the features of the genome as
      they are currently understood and provide previously unpublished analyses of many
      of the genes.

PMID- 18063097
TI  - Epidemiological modelling for monitoring and evaluation of lymphatic filariasis
      control.
AB  - Monitoring and evaluation are critically important to the scientific management
      of any parasite control programme. If a management action is prescribed,
      monitoring plays a pivotal role in assessing the effectiveness of implemented
      actions, identifying necessary adaptations for management and determining when
      management objectives are achieved. Here, we focus on the control of the vector
      borne parasitic disease, lymphatic filariasis, to show how mathematical models of
      parasite transmission can provide a scientific framework for supporting the
      optimal design of parasite control monitoring programmes by their ability to (1)
      enable the estimation of endpoint targets, (2) provide information on expected
      trends in infection due to interventions to allow rational evaluation of
      intervention effectiveness and calculation of the frequency of monitoring, (3)
      support the selection of indicators that permit reliable and statistically
      powerful measurement of the effects of interventions while minimizing costs and
      sampling intensity and (4) aid the interpretation of monitoring data for
      improving programme management and knowledge of the population dynamics of
      parasite control. The results also highlight how the use of a model-based
      monitoring framework will be vitally enhanced by adopting an adaptive management
      approach that acknowledges uncertainty and facilitates the use of monitoring data
      to learn about effective control, and which allows future decisions to be
      modified as we learn by doing. We conclude by emphasizing a pressing need to
      incorporate mathematical models coupled with changes to existing management
      systems in ongoing efforts to design and implement rational monitoring plans for
      evaluating filariasis and other parasitic disease control programmes.

PMID- 18063098
TI  - The role of helminth infections in carcinogenesis.
AB  - This review examines the significant literature on the role of helminth
      infections in carcinogenesis. Both parasitic infections and cancer have complex
      natural histories and long latent periods during which numerous exogenous and
      endogenous factors interact to obfuscate causality. Although only two helminths,
      Schistosoma haematobium and Opisthorchis viverrini, have been proven to be
      definitely carcinogenic to humans, others have been implicated in facilitating
      malignant transformation. The known mechanisms of helminth-induced cancer include
      chronic inflammation, modulation of the host immune system, inhibition of
      intracellular communication, disruption of proliferation-antiproliferation
      pathways, induction of genomic instability and stimulation of malignant stem cell
      progeny. Approximately 16% of all cancer cases worldwide are attributable to
      pathogenic agents, including schistosomes and liver flukes. This equates to
      1,375,000 preventable cancer deaths per year. Means to reduce the incidence of
      helminth-associated malignancies are discussed.

PMID- 18063099
TI  - A review of the biology of the parasitic copepod Lernaeocera branchialis (L.,
      1767) (Copepoda: Pennellidae).
AB  - This review concerns the parasitic marine copepod Lernaeocera branchialis (L.,
      1767) and provides an overview of current knowledge concerning its biology and
      host-parasite interactions. The large size and distinctive appearance of the
      metamorphosed adult female stage, coupled with the wide exploitation and
      commercial importance of its final gadoid hosts, means that this species has long
      been recognised in the scientific literature. The fact that the Atlantic cod,
      Gadus morhua L., is one of its key host species, and has itself had a major
      impact on the social and economic development of many countries bordering the
      North Atlantic for more than 10 centuries is also a factor in its widespread
      recognition. L. branchialis is recognised as a pathogen that could have major
      effects on the aquaculture industry and with gadoid (especially cod) farming
      expanding in several North Atlantic countries, there is considerable potential
      for this parasite to become a serious problem for commercial mariculture. The
      main subject areas covered are the parasite's taxonomy; the life history of the
      parasite including its life cycle, reproduction and host associations; parasite
      physiology; parasite seasonality and distribution; and the pathogenic effects of
      the parasite on its host.

PMID- 18063100
TI  - Comparison of three adjuvants used to produce polyclonal antibodies to veterinary
      drugs.
AB  - Two commercially available adjuvants, Gerbu LQ 3000 and Montanide ISA 50V, were
      assessed as potential replacements for Freund's adjuvant by evaluating their
      efficacy in the production of polyclonal antibodies to veterinary drugs in
      rabbits. The aim was to find an adjuvant that could produce a similar (or
      enhanced) immune response in the host animal without the undesirable side effects
      associated with Freund's complete and incomplete adjuvant. The assessment
      involved the examination of each injection site and the characterisation of the
      resultant antibodies with regards to antibody titre and sensitivity. It was found
      that the rabbits immunised with Gerbu adjuvant produced some of the most
      sensitive antibodies. However, titres were relatively low and adverse effects at
      injection sites were relatively common. Montanide adjuvant produced no adverse
      effects and the related antibodies were found to be of adequate sensitivity when
      compared to those from rabbits immunised with Freund's. It was concluded that
      Montanide ISA 50V could be considered as a suitable replacement to Freund's for
      the production of polyclonal antibodies, to low molecular weight compounds in
      rabbits.

PMID- 18063102
TI  - In utero exposure to maternal obesity and diabetes: animal models that identify
      and characterize implications for future health.
AB  - The developed and developing worlds are experiencing an epidemic of obesity and
      associated predisposition to diabetes. This epidemic places a major drain on
      health care resources. It is now clear that maternal obesity and gestational
      diabetes have major adverse effects on the developing fetus that lead to
      increased neonatal morbidity and mortality, as discussed elsewhere in this issue.
      Obesity in pregnancy and gestational diabetes represent a special problem, not
      only as a result of their immediate adverse effects on maternal health and
      pregnancy outcome, but also because of growing evidence for their persistent and
      deleterious effects on the developing child.

PMID- 18063103
TI  - Thrombophilia and adverse pregnancy outcome.
AB  - This article focuses on the clinical evaluation and management of women who have
      thrombophilia-related placental vascular complications, including fetal loss, pre
      eclampsia, intrauterine fetal growth restriction, and placental abruption. All
      are major causes of maternal and fetal adverse outcomes.

PMID- 18063104
TI  - Thyroid disease in pregnancy.
AB  - Twenty-seven million Americans are affected with thyroid disease, yet over half
      of this population remains undiagnosed. Thyroid disease often manifests itself
      during the reproductive period of a woman's life and is the second most common
      endocrinopathy that affects women of childbearing age. The physiologic changes of
      pregnancy can mimic thyroid disease or cause a true remission or exacerbation of
      underlying disease. In addition, thyroid hormones are key players in fetal brain
      development. Maternal, fetal and neonatal thyroid are discussed here. Moreover,
      this article serves as a review of the more common thyroid diseases that are
      encountered during pregnancy and the postnatal period, their treatments, and
      their potential effects on pregnancy.

PMID- 18063105
TI  - Maternal and fetal effects from substance use.
AB  - This article discusses a variety of issues related to pregnancies complicated by
      substance use. Drug use is most prevalent in the reproductive age population.
      Even though a reduction in substance use may occur during pregnancy, some women
      may not alter their drug use patterns until pregnancy is diagnosed. For these
      reasons, a large number of fetuses are exposed to illicit substances in utero.
      Care of substance-using pregnant women is complex, difficult, and often
      demanding. Providers must be aware of their unique psychologic and social needs,
      and the related legal and ethical ramifications surrounding pregnancy.

PMID- 18063106
TI  - Biochemical markers for the prediction of preterm delivery.
AB  - Preterm delivery is the largest contributor to perinatal morbidity and mortality
      throughout the world. In the United States, nearly 1 in every 8 infants is born
      prematurely. Although a portion of these births are indicated preterm deliveries,
      the frequency of spontaneous preterm birth has remained largely constant over the
      past 50 years.

PMID- 18063107
TI  - The risks for very low birth weight infants from multiple pregnancies.
AB  - Advances in perinatal and neonatal care in recent years have resulted in dramatic
      improvements in the rate of intact survival of preterm infants. As a result,
      neonatologists have focused on the new challenge of bringing about similar
      advances for the tiniest infants who are born at or near the current limits of
      viability. Although these tiny infants comprise only a small proportion of all
      births, the ravages of prematurity make them by far the most challenging group of
      infants who require our attention in the neonatal intensive care unit.

PMID- 18063108
TI  - Preterm labor in twins and high-order multiples.
AB  - Preterm labor (PTL) in a multiple gestation occurs frequently and is a common
      reason for preterm delivery (PTD). Management strategies for multiple gestations
      must be directed at early detection of PTL and effective strategies to delay or
      prevent PTD. Unlike singleton gestation where identification of patients at risk
      for PTL is often difficult, every multiple gestation is at risk for PTL, so all
      patients can be managed as being at risk. Although PTL is a significant cause of
      PTD, one must recognize that there are other reasons for delivery in multiple
      gestations. Clinicians must treat the whole patient and extend the pregnancy to
      the most advanced gestational age possible that is consistent with the best
      outcome.

PMID- 18063109
TI  - Diabetic-associated stillbirth: incidence, pathophysiology, and prevention.
AB  - All forms of diabetes during pregnancy are associated with an increased risk for
      stillbirth, defined as fetal death at greater than 20 weeks. The incidence of
      stillbirth in women who have diabetes has decreased dramatically with improved
      diabetes care. Diabetic-associated stillbirth is associated with hyperglycemia,
      resulting in fetal anaerobic metabolism with hypoxia and acidosis. Prevention of
      stillbirth in women who have diabetes hinges on intensive multidisciplinary
      prenatal care with control of blood sugars and appropriate fetal surveillance.

PMID- 18063111
TI  - Meconium stained fluid: approach to the mother and the baby.
AB  - Meconium aspiration syndrome (MAS) is a common problem that most pediatricians
      will encounter in the delivery room and normal newborn nursery. Approximately 13%
      of all live births are complicated by meconium stained amniotic fluid (MSAF). MAS
      is defined as respiratory distress in an infant born through MSAF whose symptoms
      cannot be otherwise explained. Optimal care for an infant born through MSAF
      involves cooperation between the obstetrician and pediatrician, each with
      separate but imperative roles.

PMID- 18063110
TI  - Perinatal arrhythmias: diagnosis and management.
AB  - The final common pathway to death in all of us is an arrhythmia, yet we still
      know far too little about the contribution of conduction abnormalities and
      arrhythmias to the compromised states of the human fetus. At no other time in the
      human life cycle is the human being at more risk of unexplained and unexpected
      death than during the prenatal period. The risk of sudden death from 20-40 weeks
      gestation is 6-12 deaths/1000 fetuses/year. This is equal to, and in some ethnic
      groups HIGHER than, the risk of death in the adult population with known coronary
      artery disease over the same time frame (6-12 deaths/1000 patients/year). Because
      only a small percentage of the United States population is pregnant each year,
      because fetal demise is not often acknowledged through public displays such as
      funerals, and finally because fetal death is culturally accepted to a much
      greater extent than it should be, this critically important area of women's
      healthcare has not had the technological advances that have been seen in adult
      cardiac intensive care and other areas of medicine. Fetal cardiac deaths may be
      preventable and the diseases that lead to these deaths are often treatable,
      especially if the sophistication of our modern ICU's could somehow be translated
      to the prenatal monitoring arena. This review article will outline recent
      advances in evaluating fetal electrophysiology, helping the perinatologist to
      better understand the nuances of fetal arrhythmias.

PMID- 18063112
TI  - Urologic problems of the neonate: an update.
AB  - During the last 2 decades of the twentieth century, maternal sonography became
      integrated into routine prenatal care. As a result, numerous anomalies are now
      detected in the fetus. This practice has had a profound influence on the
      presentation and natural history of urologic problems in the neonate. In an
      attempt to reflect the clinical scenario, this article is divided into two main
      parts: the first includes clinical questions raised by prenatally detected
      anomalies, abdominal masses, urosepsis, urinary retention, scrotal masses, and
      abnormal external genitalia; the second part is a discussion of specific
      anomalies with respect to evaluation and management, including controversies, and
      optimum timing for referral to a tertiary care center. Our knowledge regarding
      the pathophysiology and therefore treatment of these conditions is constantly
      expanding and changing.

PMID- 18063116
TI  - Fertility and reproductive disorders in female solid organ transplant recipients.
AB  - Solid organ transplantation can prolong the life of individuals with end-stage
      diseases that affect the kidney, liver, lung, heart, and pancreas. The improved
      survival of transplant recipients has led to increased attention on quality of
      life issues, including controlling fertility and having children. Perturbations
      of the hypothalamic-pituitary-ovarian axis in women with chronic renal failure or
      severe hepatic dysfunction result in anovulation and reduced fertility. Most
      often, fertility is restored with successful organ transplantation and good
      overall health. Although there are case reports of children born subsequent to
      assisted reproductive technologies (ART) in female transplant recipients, the
      approach to infertility in this population has not been described. Recognizing
      the unique medical, ethical, and psycho-social concerns involved in treating
      infertile female transplant recipients, reproductive endocrinologists must work
      with a multi-disciplinary team to ensure a successful pregnancy outcome without
      compromising graft function or maternal health. The primary goal of ART is a
      singleton pregnancy without complications, such as ovarian hyperstimulation
      syndrome, that pose greater risks in transplant recipients.

PMID- 18063113
TI  - Cleavage of myelin associated glycoprotein by matrix metalloproteinases.
AB  - Derivative myelin associated glycoprotein (dMAG) results from proteolysis of
      transmembrane MAG and can inhibit axonal growth. We have tested the ability of
      certain matrix metalloproteinases (MMPs) elevated with inflammatory and
      demyelinating diseases to cleave MAG. We show MMP-2, MMP-7 and MMP-9, but not MMP
      1, cleave recombinant human MAG. Cleavage by MMP-7 occurs at Leu 509, just distal
      to the transmembrane domain and, to a lesser extent, at Met 234. We also show
      that MMP-7 cleaves MAG expressed on the external surface of CHO cells, releasing
      fragments that accumulate in the medium over periods of up to 48 h or more and
      that are able to inhibit outgrowth by dorsal root ganglion (DRG) neurons. We
      conclude that MMPs may have the potential both to disrupt MAG dependent axon-glia
      communication and to generate bioactive fragments that can inhibit neurite
      growth.

PMID- 18063114
TI  - Sequence 168 to 177 of interphotoreceptor retinoid-binding protein (IRBP) is an
      antigenic epitope for autoreactive CD8 T cells in the B10RIII mouse.
AB  - We previously demonstrated that a significant proportion of interphotoreceptor
      retinoid-binding protein (IRBP)-specific uveitogenic T cells in the C57BL/6 mouse
      and Lewis rat express CD8. The aims of this study were to determine whether some
      of the IRBP-specific T cells in the B10RIII mouse also express CD8 and whether
      CD8 and CD4 IRBP-specific T cells in the B10RIII mouse recognize a different or
      the same antigenic epitope. Our results show that autoreactive CD8 T cells were
      abundant in B10RIII mice immunized with the uveitogenic peptide IRBP161-180.
      Using multimers of recombinant H-2D(r) molecules, we also showed that the binding
      of the H-2D(r) fusion protein to IRBP161-180-expanded CD8 T cells was dependent
      on the peptide complexed with the recombinant molecules. The use of a panel of
      truncated peptides showed that the truncated 10-mer peptide, IRBP168-177,
      retained the ability to bind to, and stimulate, IRBP161-180-specific CD8 T cells
      after complexing with a dimeric MHC class I (H-2D(r)) molecule. Finally, adoptive
      transfer of IRBP161-180-specific T cells stimulated with IRBP168-177 consistently
      induced mild, but significant, EAU in naive B10RIII mice.

PMID- 18063117
TI  - Pregnancy in renal transplant recipients.
AB  - Women with renal disease face increasing infertility and high-risk pregnancy as
      they approach end-stage renal disease due to uremia. Renal transplantation has
      provided these patients the ability to return to a better quality of life, and
      for a number of women who are of child bearing age with renal disease, it has
      restored their fertility and provided the opportunity to have children. But,
      although fertility is restored, pregnancy in these women still harbors risk to
      the mother, graft, and fetus. Selected patients who have stable graft function
      can have successful pregnancies under the supervision of a multidisciplinary team
      involving maternal fetal medicine specialists and transplant nephrologists.
      Careful observation and management are required to optimize outcome for mother
      and fetus.

PMID- 18063118
TI  - Pregnancy after liver transplantation.
AB  - There have been great strides in transplant medicine over the past few decades,
      and hundreds of pregnancies have now been reported in liver transplant
      recipients. Information on pregnancy in transplant patients has been collected
      through case reports, retrospective center-specific studies, and voluntary
      registries. Overall, favorable pregnancy outcomes have been reported for these
      patients. Pregnancy complications, however, are more common in liver transplant
      recipients than in the general population. Accordingly, pregnancies in liver
      transplant recipients should be followed by a multidisciplinary team involving
      both maternal fetal medicine specialists and transplant physicians. This chapter
      outlines the available data on the maternal and obstetrical outcomes of
      pregnancies in liver transplant recipients, and will review guidelines for
      management of these high-risk pregnancies.

PMID- 18063119
TI  - Pregnancy after thoracic organ transplantation.
AB  - A growing number of heart, heart-lung, or lung transplant recipients are women of
      reproductive age. Fertility and pregnancy are important issues in this group of
      patients and often pose complex medical, psychosocial, and ethical problems. Many
      successful pregnancy outcomes have been reported following heart or lung
      transplantation. Nevertheless, these patients are at risk of certain maternal,
      fetal, and neonatal complications, including hypertension, preeclampsia,
      infection, preterm birth, and low birth weight. The physiological changes that
      occur in pregnancy are generally well tolerated by patients who have undergone
      thoracic organ transplant(s). The risk of allograft rejection during and after
      pregnancy is significant, and it is important to maintain an adequate level of
      immunosuppression. Pregnancies among lung transplant recipients are at higher
      risk for certain complications. The rate for graft rejection, independent of
      pregnancy status, is higher in this population. The long-term graft and patient
      outcomes citing a 50% 5-year mortality will be critical while counseling these
      patients regarding the impact of pregnancy on survival, and the ability to
      participate in raising the child. A multi-disciplinary team, involving
      specialists in maternal fetal medicine, cardiology or pulmonary medicine,
      transplant medicine, anesthesiology, high-risk nursing, neonatology, psychology,
      genetics, and social service, is crucial to the care of these patients. This team
      approach should be initiated at the time of pretransplant and preconception
      counseling and be continued through the prenatal and postpartum periods. The
      management plan should be individualized according to the status of the mother,
      the fetus, and the allograft. For most cases, given the need for close
      collaboration and frequent monitoring, these patients are best managed at their
      primary transplant institution in collaboration with local or referring
      physicians.

PMID- 18063120
TI  - Immunosuppressant therapy in pregnant organ transplant recipients.
AB  - Transplant recipients are becoming pregnant with increasing frequency, and
      successful pregnancy outcomes have now been reported for women with all types of
      solid organ transplants. To prevent rejection of the transplanted organ, these
      patients are maintained on a life-long immunosuppressive regimen that must also
      be continued through pregnancy. Controlled human studies of the safety of these
      drugs have not been conducted, and knowledge regarding the pharmacokinetics of
      these medications in pregnancy is limited. Significant experience and safety data
      regarding the use of some of the more common immunosuppressants in pregnancy
      have, however, been accumulated from large case series and national registries.
      These observational studies suggest that successful pregnancy outcomes are
      possible in female organ transplant recipients, although sporadic adverse
      outcomes have been reported after immunosuppressant use in pregnancy. In this
      chapter, we will outline the information available regarding the use of
      immunosuppressive medications in pregnant transplant recipients as well as
      general concepts regarding fetal exposure to immunosuppressants.

PMID- 18063121
TI  - Contraception for the transplant patient.
AB  - Patients who have had an organ transplant have a need for highly effective
      contraception. Intrauterine devices, depo-medroxyprogesterone acetate, and
      implantable etonorgestrel have the highest efficacy combined with the least
      chance of interaction with antirejection medication regimens. Combined hormonal
      contraceptives and progestin-only pills are also acceptable methods for patients
      who do not have other contraindications to their use. Barrier method use should
      be advocated for any patient who is entering a new sexual relationship and as an
      adjunct to other methods. Consultation with a gynecologist experienced with the
      provision of contraceptives to medically complicated patients is advised for all
      women of reproductive age who have received an organ transplant.

PMID- 18063122
TI  - Otosclerosis in children and adolescents: a clinical and CT-scan survey with
      review of the literature.
AB  - OBJECTIVE: To assess the role of the CT-scan in the preoperative evaluation of
      juvenile otosclerosis and to study additional outcome data. DESIGN AND SETTING:
      We performed a retrospective case series study from an academic referral hospital
      using data from 1992 to 2005. PATIENTS AND METHODS: We selected patients younger
      than 18-year-old who had undergone primary stapedectomy for otosclerosis among
      the 10 stapedectomies performed over the study period and analyzed the patients'
      systematic pre- and post-operative audiograms and CT-scan findings. RESULTS: For
      this survey, complete data was available for 7 children, totaling 10 primary
      stapedectomies for otosclerosis. Their ages at diagnosis ranged from 10 to 17
      years. In 4 children, CT-scan demonstrated bilateral findings typical of
      otosclerosis: poorly calcified foci near the fissula ante fenestram, associated
      with a hypodense edging surrounding the labyrinthine capsule in 2 children. The
      youngest patient had no CT-scan abnormalities. Stapedectomy was performed in one
      case and laser stapedotomy in 9 cases. Seven children were immediately improved
      following surgery and no postoperative facial palsy or prolonged vertigo was
      reported. The mean (S.D.) postoperative ABG was 6.5dB (+/-3.7). The mean closure
      was 19dB (+/-11.2). The mean change in high-tone bone conduction level was 1.8dB
      (+/-7.5). Six children had a postoperative ABG less than 10dB while in one, the
      ABG was inferior to 20dB. CONCLUSION: Preoperative CT-scan is useful for the
      preoperative diagnosis of otosclerosis in children. The images seen must be
      distinguished from other footplate pathologies or deformities of the ossicular
      chain which are often associated with poorer surgical results. This survey
      provides additional evidence that stapes surgery is an effective procedure for
      treating juvenile otosclerosis.

PMID- 18063123
TI  - The impact of gender and age on voice related quality of life in children:
      normative data.
AB  - OBJECTIVES: Although several instruments are available to measure voice quality
      in children, their application to a normal population and major demographic
      subgroups has not been described. It is hypothesized that there is no measurable
      difference in self-reported voice related quality of life between gender and age
      groups within a population of normal children as measured by the Pediatric Voice
      Related Quality of Life (PVRQOL) instrument. METHODS: The PVRQOL instrument was
      used to prospectively survey a cohort of children in series at the Wisconsin
      State Fair. PVRQOL scores may range from 0 (complete dysfunction) to 100 (no
      dysfunction). Comparisons were made between age and gender groups in order to
      test the null hypothesis. RESULTS: Of the 100 surveys completed by parents of
      children, 93 were performed correctly and had evaluable data (age range 2-17
      years, mean 9.8). The mean PVRQOL score was 97.0+/-5.6. There was no difference
      between females and males (97.5+/-5.83 versus 96.5+/-5.3, p>0.05, unpaired t
      test); however, within the pre-pubescent school age subjects, a diminished PVRQOL
      was reported for boys (95.5+/-6.37) as compared to girls (98.5+/-3.10, p<0.05,
      unpaired t-test). Further subgroup analysis revealed no significant difference
      (p>0.05) between age groups or gender. CONCLUSIONS: Amongst a random group of
      children without voice complaints queried outside of a medical center, self
      reported PVRQOL showed no significant dysfunction. This is the first report of
      gender and age-specific normative PVRQOL data in children. A score of 86 or
      greater on the PVRQOL instrument represents a normal voice related quality of
      life.

PMID- 18063124
TI  - Specific detection of small ruminant lentiviral nucleic acid sequences located in
      the proviral long terminal repeat and leader-gag regions using real-time
      polymerase chain reaction.
AB  - Real-time polymerase chain reaction (RT-PCR) detection of proviral nucleic acid
      sequences of small ruminant lentiviruses (SRLV) in blood samples was developed
      and evaluated. Priming oligonucleotides were designed on the highly conserved 5'
      untranslated leader-gag region while those on the long terminal repeat (LTR)
      assay were derived from literature. DNA was extracted from the buffycoat
      interlayer of centrifuged blood samples. Real-time PCR was performed by means of
      LightCycler technology (Roche Applied Science) using melting temperature analysis
      (SYBR Green I) for detection. Results were compared with those of serology using
      samples from Dutch sheep and goat flocks with known SRLV statuses, with
      sequential samples from a natural transmission experiment and samples from
      different regions in Norway, France, Spain and Italy. Real-time PCR testing,
      especially the application of oligonucleotides for priming the leader-gag region
      appeared promising in detecting SRLV specific proviral DNA in blood samples from
      both sheep and goats.

PMID- 18063125
TI  - Development of a multiplexed PCR detection method for Barley and Cereal yellow
      dwarf viruses, Wheat spindle streak virus, Wheat streak mosaic virus and Soil
      borne wheat mosaic virus.
AB  - Barley and Cereal yellow dwarf viruses (B/CYDVs), Wheat spindle streak mosaic
      (WSSMV), Soil-borne wheat mosaic virus (SBWMV) and Wheat streak mosaic virus
      (WSMV) constitute the most economically important group of wheat viruses. In this
      paper, a multiplex reverse transcription polymerase chain reaction (M-RT-PCR)
      method was developed for the simultaneous detection and discrimination of eight
      viruses: five strains of B/CYDVs, WSSMV, SBWMV and WSMV. The protocol uses
      specific primer sets for each virus producing five distinct fragments 295, 175,
      400, 237, and 365 bp, indicating the presence of two strains of BYDVs, -PAV, 
      MAV, CYDV-RPV and two unassigned Luteoviridae BYDV-SGV and -RMV, respectively.
      This system also readily detected WSSMV, SBWMV and WSMV specific amplicons at
      154, 219 and 193 bp, respectively. The amplification specificity of these primers
      was tested against a range of field samples from different parts of United
      States. The protocol also utilizes fluorescently tagged primers that can
      streamline the detection of each virus through capillary electrophoresis. This
      study fulfills the need for a rapid and specific wheat virus diagnostic tool that
      also has the potential for investigating the epidemiology of these viral
      diseases.

PMID- 18063126
TI  - National prevalence of methicillin-resistant Staphylococcus aureus in inpatients
      at US health care facilities, 2006.
AB  - BACKGROUND: Despite methicillin-resistant Staphylococcus aureus (MRSA) being
      endemic in virtually all US health care facilities, there are no data on the
      prevalence of MRSA in US health care facilities. METHODS: We conducted a national
      prevalence survey of MRSA in inpatients at US health care facilities. The survey
      was developed, received institutional review board approval, and then distributed
      to all members of the Association for Professionals in Infection Control and
      Epidemiology, Inc. (APIC). Members were asked to complete the survey on one day
      during the period October 1 to November 16, 2006, reporting the number of
      inpatients with MRSA infection or colonization and facility-specific information.
      RESULTS: Personnel at 1237 hospitals completed the survey. Complete facility data
      were provided for 1187 (96%) of these health care facilities. All states were
      represented (mean, 23 facilities per state; range, 1-99). Respondents reported
      8654 MRSA-colonized/infected patients in 187,058 inpatients; the overall MRSA
      prevalence rate was 46.3 per 1000 inpatients (34 infections and 12 colonizations
      per 1000 inpatients). Active MRSA surveillance testing was conducted by 29% of
      respondents: 54% used routine media, 38% used selective media, and 8% used
      polymerase chain reaction. Detailed data were provided on 7994 (92.4%) MRSA
      colonized/infected patients. Our data suggest that approximately 70% of isolates
      were more consistent with health care-associated MRSA (HA-MRSA) than community
      associated MRSA. CONCLUSION: Our survey documents a much higher MRSA prevalence
      rate than previous studies using different methodologies. The majority of MRSA in
      inpatients appears to be HA-MRSA. Given that most facilities did not perform
      active surveillance testing, these are minimum estimates of the national burden
      of MRSA in US health care facilities.

PMID- 18063127
TI  - The categorization of prior antibiotic use: impact on the identification of risk
      factors for drug resistance in case control studies.
AB  - BACKGROUND: Analytic approaches to the identification of risk factors for the
      development of drug resistance vary and may affect study results. Using
      fluroquinolone-resistant Pseudomonas aeruginosa (FQRPA) and imipenem-resistant P.
      aeruginosa as models (IRPA), we aimed to examine the effect of different
      approaches to classification of prior antibiotic use (i.e., class versus
      spectrum) on the identification of risk factors for antibiotic resistance.
      METHODS: Case-control studies to identify risk factors for FQRPA and IRPA were
      performed. In each, two analytic models were utilized. In the first, prior
      antibiotic use was classified by class, and in the other, prior antibiotic use
      was classified by spectrum of activity. Risk factors identified by the two models
      were compared qualitatively for each resistant organism. RESULTS: 879 isolates of
      P. aeruginosa were included in the case-control studies. Risk factors for FQRPA
      and IRPA identified in multivariable analyses differed based on which method of
      classification of prior antibiotic use was utilized. CONCLUSIONS: The
      identification risk factors for the development of drug-resistant organisms could
      depend on the method of classification of prior antibiotic use. In studies of
      risk factors for resistant infections, the approach to classification of prior
      antibiotic use should be clearly stated and justified.

PMID- 18063128
TI  - Implementation of an intensified infection control program to reduce MRSA
      transmissions in a German tertiary care hospital.
AB  - BACKGROUND: Germany has witnessed increasing national methicillin-resistant
      Staphylococcus aureus (MRSA) rates during the past 2 decades. In our 900-bed
      tertiary care community hospital, a similar increase was noted during the period
      from 1994 to 2002, although single-room isolation and decolonization therapy were
      the standard of care. METHODS: An intensified infection control program aimed at
      the reduction of nosocomial MRSA transmissions was developed in 2002 and
      translated into clinical practice in 2003. Essential components of the program
      were a detailed written MRSA standard, acquisition of signal-colored isolation
      gowns and storage carts facilitating the use of separate supplies for MRSA
      patients, intensified surveillance and feedback of MRSA data, "flagging" of
      formerly positive MRSA patients, and a general MRSA screening policy for all
      newly admitted patients on the surgical intensive care unit (ICU). The effect of
      the program was monitored by continuous surveillance of MRSA cases on all wards.
      The transmission index was defined as the ratio between secondary and "imported"
      MRSA cases. RESULTS: Comparing the preintervention (2002) and postintervention
      (2005-2006) periods, the total number of MRSA patients, MRSA rates on the ICUs,
      and invasive MRSA infections on the ICUs were reduced. The MRSA transmission
      index fell from 2.1 (2002) to 0.8 (2006). The rate of deep incisional and
      organ/space infections due to MRSA occurring after orthopedic surgery was lowered
      from 0.74 to 0.15%. CONCLUSIONS: Our data indicate that the efficacy of single
      room isolation and decolonization therapy can be strongly enhanced by means of a
      multicomponent, comprehensive MRSA control program. The program was effective
      despite an increasing "import" of new MRSA cases. Programs of this type may be
      suited to achieve a downward turn of MRSA figures in Germany.

PMID- 18063129
TI  - A controlled trial of universal gloving versus contact precautions for preventing
      the transmission of multidrug-resistant organisms.
AB  - BACKGROUND: Contact precautions are recommended to reduce the transmission of
      multidrug-resistant organisms. However, the optimal method for control of
      multidrug-resistant organisms remains unclear. METHODS: A controlled trial was
      conducted in a medical intensive care unit. Phase 1 was a 3-month period of
      standard practice in which patients were placed in contact precautions per
      Centers for Disease Control and Prevention guidelines. In the second 3 months,
      phase 2, gloves were required for all patient contact, and no patients were
      placed in contact precautions. RESULTS: Compliance with contact precautions in
      phase 1 versus universal gloving in phase 2 was 75.7% versus 87.0%, respectively
      (P < .001). Hand hygiene compliance before patient care was significantly higher
      in phase 1 when compared with phase 2 (18.7% vs 11.4%, respectively, P < .001).
      Hand hygiene compliance after patient care was 57.7% in phase 1 versus 52.5% in
      phase 2 (P = .011). Nosocomial infection rates per 1000 device-days in phase 1
      versus phase 2 were as follows: bloodstream infection, 6.2 versus 14.1,
      respectively (P < .001); urinary tract infection, 4.3 versus 7.4, respectively (P
      < .001); and ventilator-associated pneumonia, 0 versus 2.3, respectively (P <
      .001). There were no differences in vancomycin-resistant enterococci or
      methicillin-resistant Staphylococcus aureus acquisition in the 2 study phases;
      however, in both phases, the majority of vancomycin-resistant enterococci and
      methicillin-resistant Staphylococcus aureus conversions were clonal. CONCLUSION:
      Compliance with universal gloving was significantly greater than compliance with
      contact precautions. However, greater compliance with hand hygiene was observed
      in the contact precautions phase. Measures must be in place to both increase and
      sustain hand hygiene compliance so as to minimize the risk of nosocomial cross
      transmission before reevaluating the concept of replacing contact precautions
      with universal gloving.

PMID- 18063130
TI  - Spreading the word, not the infection: reaching hospitalists about the prevention
      of antimicrobial resistance.
AB  - BACKGROUND: To reach and engage hospitalists in the prevention of antimicrobial
      resistance, the Society of Hospital Medicine and the Centers for Disease Control
      and Prevention developed and conducted a quality improvement workshop based on
      the Centers for Disease Control and Prevention's Campaign to Prevent
      Antimicrobial Resistance in Healthcare Settings. METHODS: We aimed to examine
      motivating factors, perceived barriers, and cues to action for hospitalists to
      learn about and engage in the prevention of antimicrobial resistance and to
      determine whether a workshop can facilitate the implementation of a quality
      improvement project. Using the Health Belief Model as a theoretical framework, we
      interviewed hospitalists who attended (attendees) and did not attend
      (nonattendees) the workshop. Data were qualitatively coded and analyzed. RESULTS:
      Nine attendees and 10 nonattendees participated in interviews. Motivating factors
      for attending the workshop included an interest in the topic of quality
      improvement and antimicrobial resistance prevention, the promotion of the
      workshop by institutions and colleagues, the opportunity to network with
      colleagues, and the qualifications of the presenter. Barriers to involvement in
      quality improvement efforts and the prevention of antimicrobial resistance for
      both attendees and nonattendees included perceived lack of time, other
      institutional priorities, and lack of administrative and institutional support.
      Attendees and nonattendees also identified perceived effective and preferred
      methods for receiving information about antimicrobial resistance, such as
      workshops and presentations, e-mail, institutional involvement, and the Internet.
      Overall, attendees thought that the workshop could be effective in facilitating
      the implementation of a quality improvement project. CONCLUSION: By considering
      factors that influence behavioral change, interventions, such as the Society of
      Hospital Medicine workshop, have the ability to reach and engage clinicians such
      as hospitalists in quality improvement efforts to prevent antimicrobial
      resistance and improve adherence to infection control strategies. Furthermore,
      this study demonstrated that the Health Belief Model can provide an applicable
      framework for examining factors that influence clinician behavior.

PMID- 18063131
TI  - Infection control resources in Iowa.
AB  - BACKGROUND: The duties of infection control professionals (ICPs) have increased
      over time, but resources have not increased substantially. Numerous states have
      passed or have considered mandatory reporting laws for health care-associated
      infections. Such laws would increase ICPs' work further. METHODS: We conducted
      two surveys of ICPs in Iowa to determine their current responsibilities and
      resources and to estimate the resources they would need if they were required to
      report all nosocomial infections to the state. RESULTS: Most hospitals had less
      than 1 full time equivalent performing infection control (mean = 0.64). Many
      respondents had several roles within the hospital. Surveillance methods and scope
      varied by hospital size. Most ICPs did not use catheter days as the denominator
      for rates of bloodstream infections. Over 50% of Iowa's hospitals are critical
      access hospitals, most of which did not have intensive care units, and most had
      very few patients with central venous catheters. CONCLUSIONS: Hospitals in Iowa
      have limited resources for infection control. "One size fits all" public
      reporting systems are not appropriate for states like Iowa that have a few large
      hospitals and many small hospitals.

PMID- 18063132
TI  - Dissemination of the CDC's Hand Hygiene Guideline and impact on infection rates.
AB  - BACKGROUND: The diffusion of national evidence-based practice guidelines and
      their impact on patient outcomes often go unmeasured. METHODS: Our objectives
      were to (1) evaluate implementation and compliance with clinical practices
      recommended in the new Centers for Disease Control and Prevention (CDC) Hand
      Hygiene Guideline, (2) compare rates of health care-associated infections (HAI)
      before and after implementation of the Guideline recommendations, and (3) examine
      the patterns and correlates of changes in rates of HAI. We used pre- and post
      Guideline implementation site visits and surveys in the setting of 40 US
      hospitals--members of the National Nosocomial Infections Surveillance System--and
      measured HAI rates 1 year before and after publication of the CDC Guideline and
      used direct observation of hand hygiene compliance and Guideline implementation
      scores. RESULTS: All study hospitals had changed their policies and procedures
      and provided products in compliance with Guideline recommendations; 89.8% of 1359
      staff members surveyed anonymously reported that they were familiar with the
      Guideline. However, in 44.2% of the hospitals (19/40), there was no evidence of a
      multidisciplinary program to improve compliance. Hand hygiene rates remained low
      (mean, 56.6%). Rates of central line-associated bloodstream infections were
      significantly lower in hospitals with higher rates of hand hygiene (P < .001). No
      impact of Guideline implementation or hand hygiene compliance on other HAI rates
      was identified. Other factors occurring over time could affect rates of HAI.
      Observed hand hygiene compliance rates were likely to overestimate rates in
      actual practice. The study may have been of too short duration to detect the
      impact of a practice guideline. CONCLUSION: Wide dissemination of this Guideline
      was not sufficient to change practice. Only some hospitals had initiated
      multidisciplinary programs; practice change is unlikely without such
      multidisciplinary efforts and explicit administrative support.

PMID- 18063133
TI  - Evaluation of hand hygiene adherence in a tertiary hospital.
AB  - BACKGROUND: Although hand hygiene is the most important measure in the prevention
      of nosocomial infection, adherence to recommendations among health care workers
      (HCW) is low. Evaluation of compliance with hand hygiene was carried out in a
      Spanish teaching hospital. METHODS: In 2005, adherence to hand hygiene was
      evaluated hospital wide through direct observation, collecting data on hand
      hygiene carried out whenever indicated (opportunity for hand hygiene). Compliance
      was defined as handwashing/disinfection in an opportunity for hand hygiene
      according to hospital protocols. The results were analyzed using mixed effects
      models, with the HCW observed as the random effect. RESULTS: A total of 1254
      opportunities for hand hygiene were observed in 247 HCWs. Mean compliance was
      20%. Although few differences were observed among types of HCW, compliance varied
      according to hospital area (69% in the intensive care unit [ICU]) and timing with
      respect to patient contact (compliance after contact was twice that before
      contact). Multivariate analyses revealed a protective odds ratio (OR) for
      nonadherence in ICUs (OR, 0.04; 95% confidence interval (95% CI): 0.01-0.10) and
      after patient contact (OR, 0.25; 95% CI: 0.17-0.38). CONCLUSION: Low adherence
      observed suggests that new interventions should focus in modification of HCWs'
      habits and attitudes, working at several levels: individual and institutional.

PMID- 18063134
TI  - Airflow and droplet spreading around oxygen masks: a simulation model for
      infection control research.
AB  - BACKGROUND: Respiratory assist devices, such as oxygen masks, may enhance the
      potential to spread infectious aerosols from patients with respiratory
      infections. METHODS: A technique was developed to visualize exhaled aerosols
      during simulated patients' use of oxygen masks in a health care setting and
      tested using the simple, the nonrebreathing, and the Venturi oxygen masks. A
      smoke tracer was introduced into one of the lungs of the model to enable it to
      mix with the incoming oxygen and then to be further inhaled/exhaled by the model
      according to a variety of realistic respiratory settings (14, 24, and 30 breaths
      per minute, with tidal volumes of 500, 330, 235 mL, respectively) and oxygen
      supply flow rates (between 6 and 15 liters per minute). Digital recordings of
      these exhaled airflow patterns allowed approximate distances to be estimated for
      the extent of the visible exhaled air plumes emitted from each oxygen mask type
      at these settings. RESULTS: It was found that the simple, the nonrebreathing, and
      the Venturi-type oxygen masks produced exhaled smoke plumes over minimum
      distances of 0.08 to 0.21 m, 0.23 to 0.36 m, and 0.26 to 0.40 m, respectively.
      CONCLUSION: Health care workers may therefore consider any area within at least
      0.4 m of a patient using such oxygen masks to be a potential nosocomial hazard
      zone.

PMID- 18063135
TI  - Going Dotty: a practical guide for installing new hand hygiene products.
AB  - This report distills our experiences coordinating the installation of a new
      commercial line of hand hygiene products in a large, integrated health care
      region in Western Canada into a practical guide that can benefit infection
      control professionals. Some key considerations while managing such a large hand
      hygiene products installation are stakeholder collaboration, management of
      occupational hand dermatitis, housekeeping support, and communication.

PMID- 18063136
TI  - A survey of hand hygiene practices on a residential college campus.
AB  - BACKGROUND: Upper respiratory tract infections and gastrointestinal tract
      infections are the cause of a significant level of illness on college campuses.
      However, preventative measures such as handwashing and hand sanitation are often
      not well-supported, understood, or practiced on campus. METHODS: A confidential,
      self-administered on-line survey was performed during April-May 2006. RESULTS:
      Nine hundred and ninety-four participants completed the survey. Of these, 49%
      were undergraduates, 30% were graduates, and 34% lived in residence halls on
      campus. CONCLUSIONS: We recommend the importance of creating an awareness of
      proper hand hygiene practices as they relate to the everyday context of a college
      campus. In addition, we believe there is a need for hand hygiene education
      targeted at students. Finally, we strongly recommend that college authorities
      provide soap and a means of hand drying in all residential bathrooms.

PMID- 18063137
TI  - MRSA infections in smaller hospitals, Victoria, Australia.
AB  - BACKGROUND: Infections caused by methicillin-resistant Staphylococcus aureus
      (MRSA) cause significant morbidity, mortality, and associated costs. METHODS:
      Trained infection control (IC) nurses in 84 smaller (<100 acute beds) hospitals
      during a 20-month period collected data on MRSA infections. RESULTS: The
      aggregate rate for all MRSA infections confirmed by the Victorian Hospital
      Acquired Infection Surveillance System Coordinating Centre IC nurse was 1.5 per
      10,000 acute care occupied bed days (OBDs) (95% CI: 1.2-1.8). MRSA infections of
      0.5 per 10,000 OBDs were detected >48 hours after admission (95% CI: 0.3-0.7).
      The aggregate rate for MRSA infections in sterile sites was 0.2 per 10,000 OBDs
      (95% CI: 0.0-0.4) and in nonsterile sites was 1.3 per 10,000 OBDs (95% CI: 1.0
      1.6). CONCLUSION: The results suggested that serious MRSA infections in
      Victoria's smaller hospitals are an infrequent event. Most are "inherited" either
      from the community or other health care facilities.

PMID- 18063139
TI  - ICV leptin effects on spontaneous physical activity and feeding behavior in rats.
AB  - Although leptin causes negative energy balance by reducing food intake and
      increasing energy expenditure, the effect of leptin on spontaneous physical
      activity (SPA) is not clearly established. To test the hypothesis that leptin
      enhances SPA in rats, male Sprague-Dawley rats were injected
      intracerebroventricularly (ICV) with either 10mug of leptin or artificial
      cerebrospinal fluid (aCSF) before dark onset (12:00h) once daily for 5 successive
      days. The rats were individually housed in behavioral monitoring cages to measure
      feeding behavior and SPA throughout the study. Both groups had a diurnal pattern
      of SPA being low during the light period and high during the dark period.
      Specifically, there were two peaks of SPA during the dark period, with the first
      peak taking place around the dark onset and the second occurring approximately 6h
      towards the light onset. Leptin treatment resulted in a significant increase in
      SPA whether or not it was expressed in terms of light-dark, daily or diurnal
      basis. Increased SPA was consistently observed throughout the entire 5-day study
      in spite of the fact that the rats were consistently eating less and losing body
      weight. With reduction in weight of fat pads and increase in apoptosis of fat
      pads but no change in body temperature, leptin decreased size, duration and
      number of meals without altering eating rate, thereby increasing satiety. Our
      data show that increased activity is a key determinant in negative energy balance
      induced by leptin, which cannot be accounted for solely by the leptin-induced
      food intake reduction.

PMID- 18063138
TI  - Spatial memory alterations in three models of hepatic encephalopathy.
AB  - A behavioural evaluation was carried out on three chronic models of hepatic
      encephalopathy: two models of type B HE, portacaval shunt (PCS) and portal
      hypertension (PH) and one of type C HE with cirrhosis and portal hypertension
      from thioacetamide intoxication (TAA). The tasks selected cover a wide range of
      behaviours related to: locomotion (rotarod-accelerod test), anxiety (open field
      and elevated plus maze) and memory (Morris water maze). The results indicate that
      neither locomotor activity nor anxiety was affected in our models, in comparison
      with their respective controls. However, this is not the case for the mnesic
      tasks. Hence, the PCS and TAA groups displayed a severe alteration in spatial
      reference memory and cannot correctly perform the Morris maze task, while this
      alteration is less severe in the PH group. On the contrary, the PH group revealed
      a deficit in spatial working memory, like the TAA group, but this does not occur
      in subjects with PCS. These results reveal a double dissociation in spatial
      reference memory and spatial working memory between the PCS and PH groups, which
      would be of great interest to study about cerebral causes and substrates of the
      alterations accompanying HE.

PMID- 18063140
TI  - Galactosilated dopamine increases attention without reducing activity in C57BL/6
      mice.
AB  - Different strategies can be used to carry dopamine into the brain such as L-Dopa
      precursors or galactosilated form of DA (GAL-DA). The aim of this study was to
      investigate whether GAL-DA would reduce hyperactivity and increase non-selective
      attention (NSA) in a mouse model of attention deficit hyperactivity disorder
      (ADHD), as, i.e. C57BL/6 as did in NHE rats. Here we report that GAL-DA increases
      NSA in a spatial novelty in C57BL/6 mice. They received a single i.p. injection
      of GAL-DA (10 mg/kg or 100 mg/kg) or equimolar galactose vehicle. Another mouse
      strain the Swiss albino was introduced as inbred control group. Three hours after
      last injection mice were tested in a Lat-maze for 30-min. Behaviour was analyzed
      for horizontal (traveled distance) and vertical activity (orienting frequency and
      scanning durations) which shares cognitive and non-cognitive nature,
      respectively. Ten milligram per kilograms of GAL-DA, increases scanning duration
      in C57BL/6 mice. Thus a low dose of GAL-DA increases NSA without reducing
      hyperactivity in this mouse model of ADHD.

PMID- 18063141
TI  - Functional properties of the four Atlantic salmon (Salmo salar) aryl hydrocarbon
      receptor type 2 (AHR2) isoforms.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      through which organochlorine contaminants including 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD), and some polycyclic aromatic hydrocarbons induce toxicity and
      altered gene expression. Atlantic salmon has multiple AHR genes, of which two
      belong to the AHR1 clade and four belong to the AHR2 clade. The four AHR2 forms
      (alpha, beta, gamma, delta) are more highly expressed than the AHR1 (alpha,
      beta,) forms and all six AHRs are highly similar in pairs, likely originating
      from a whole-genome duplication in the salmonid ancestor. It has been speculated
      that having multiple AHRs contributes to the very high sensitivity of salmonid
      species to TCDD and related chemicals. To test the hypothesis that all four
      salmon AHR2 proteins are expressed and functional, we measured mRNA transcription
      for each AHR2 in several tissues, cloned the cDNAs and evaluated the functional
      properties of the expressed proteins. Analysis by real-time PCR revealed that the
      receptors showed differences in transcript levels among salmon tissues and that
      in general AHR2alpha was transcribed at higher levels than the other three AHR2s.
      Velocity sedimentation analysis showed that all four in vitro-expressed AHR2
      proteins exhibit specific, high-affinity binding of [(3)H]TCDD. When expressed in
      COS-7 cells, all four AHR2 proteins were able to drive the expression of a
      reporter gene under control of murine CYP1A1 enhancer elements. From EC(50)
      values determined in TCDD concentration-response experiments, all four salmon
      AHR2s show similar sensitivity to TCDD. In summary, all four Atlantic salmon AHR2
      appear to function in AHR-mediated signaling, suggesting that all four proteins
      are involved in TCDD-mediated toxicity.

PMID- 18063142
TI  - The effect of starving and feeding on copper toxicity and uptake in Cu acclimated
      and non-acclimated carp.
AB  - Common carp (Cyprinus carpio) were fed two different food rations: 0.5% body
      weight (low ration, LR) and 5% body weight (high ration, HR) and were either
      acclimated to sublethal copper (1 microM) for 28 days in softened Antwerp city
      tap water or not acclimated. Fish were exposed for 10 days to high Cu levels
      using four different concentrations (3.5, 6, 10, and 15 microM) before and after
      the Cu acclimation. Fish tolerance against Cu exposure was evaluated, and gill,
      liver, and carcass Cu and sodium levels were measured in dead and surviving fish.
      HR fish were twice as sensitive as LR fish in both tests. The 96h median lethal
      concentration (LC50) values for the non-acclimated LR and HR fish were 8.46+/
      2.79 and 4.34+/-0.82 microM, respectively. The fish became more resistant to low
      Cu concentrations after Cu acclimation and the LC50 values were slightly
      increased, reaching 9.20+/-1.56 microM and 5.01+/-1.93 in LR and HR fish
      accordingly. Cu concentrations in the gills, liver, and carcass were
      significantly elevated in response to the short-term Cu exposure, and were
      significantly higher in LR fish than in HR fish. High Cu levels caused a net loss
      of sodium resulting in a severe ion regulatory disturbance. The rate of sodium
      loss increased linearly with increasing exposure concentrations. Cu acclimation
      resulted in reduced sodium loss and increased the resistance and tolerance to Cu
      toxicity.

PMID- 18063143
TI  - Copper-induced oxidative stress in rainbow trout gill cells.
AB  - Copper is known to pose a serious threat to aquatic organisms. However, the
      mechanisms of its toxicity still remain unclear. Cu is known to exert its
      toxicity partly due to the formation of reactive oxygen species (ROS). The
      purpose of this work was therefore to link the exposure to copper at pH 6 and 7
      to cellular formation of ROS and effects like cell viability and genotoxicity
      using the rainbow trout gill cell line RTgill-W1. To relate effects to
      bioavailable copper, free Cu(2+) concentrations in the medium were calculated
      using the programm ChemEQL 3.0. 2',7'-Dichlorodihydrofluorescein-diacetate
      (H(2)DCF-DA) was used as cell-permeant indicator of ROS formation. Cell viability
      was assessed using the fluorogenic probe 5-carboxyfluorescein diacetate
      acetoxymethyl ester (CFDA-AM). DNA strand breaks were assessed using the comet
      assay, and lipid peroxidation was investigated using the thiobarbituric acid
      reactive substances assay (TBARS). Copper treatment resulted in a dose-dependent
      elevation in cytotoxicity and formation of cellular ROS. Cell viability was
      significantly reduced at total copper (Cu(T)) concentrations of 5 microM
      (corresponding to a free Cu(2+) of 0.11 microM at pH 7) and higher, resulting in
      an EC(50) of Cu(T)=29.2 microM (Cu(2+)=0.63 microM, pH 7). Neither an impairment
      concerning the viability of control cells due to growth at pH 6 was observed nor
      significant differences for cytotoxicity in cells exposed to the same nominal
      Cu(T) concentrations at pH 6 compared to pH 7. Cellular ROS concentrations
      increased significantly and decreased with loss of cell viability. After
      normalizing ROS formation to cell viability, ROS induction up to 25-35-fold
      compared to the control was detected, but mainly for rather high concentrations
      (Cu(T) > or = 100 microM; Cu(2+) > or = 2.2 microM, pH 7). ROS formation rates
      were slightly higher when cells were exposed to Cu at pH 6 compared to pH 7,
      correlating with the higher free Cu(2+) concentrations. A significant induction
      of DNA strand breaks was noted at Cu(T) of 1 and 2.5 microM with greater effects
      at pH 6 due to higher free Cu(2+) concentrations than at pH 7. No effects on
      lipid peroxidation were observed. These results lead to the hypothesis that
      copper-induced loss in viability and genotoxicity in trout gill cells are
      partially triggered by the generation of ROS and related to the free Cu(2+).

PMID- 18063144
TI  - Global quantitative analysis of protein expression and phosphorylation status in
      the liver of the medaka fish (Oryzias latipes) exposed to microcystin-LR I.
      Balneation study.
AB  - Microcystins (MCs) are hepatotoxins with potent inhibitor activity of protein
      phosphatases PP1 and PP2A. These non-ribosomal peptides are getting more and more
      attention due to their acute toxicity and potent tumor-promoting activity. These
      toxins are produced by freshwater cyanobacteria. The most toxic and most commonly
      encountered variant in aquatic environment is MC-LR (MC Leucine-Arginine). It has
      been used for toxicological investigations on the liver of intoxicated medaka.
      Differential proteome as well as differential phosphoproteome analyses have been
      performed for providing new information on early responses to the toxin. The
      experiments are also aiming at selecting biomarkers of MC-LR exposure. In the 2D
      electrophoresis gel protein maps from cytosol of liver cells of animals exposed
      or non-exposed to the cyanotoxin, 15 spots showed a significant increase or
      decrease of their stain signal either in specific phosphoprotein stain or total
      protein stain. Thirteen of these proteins have been identified by mass
      spectrometry. Among them, phenylalanine hydroxylase (PAH) and keratin 18 type I
      showed variations in phosphorylation stain in possible agreement with inhibition
      of PP2A activity. The other identified proteins exhibited variations in their
      expression level. The identified proteins appear to be involved in cytoskeleton
      assembly, cell signalling, oxidative stress and apoptosis. Such results confirm
      that proteomics and phosphoproteomics approaches may become valuable tools to
      identify signalling pathways implied in MC-LR effects. From accumulated data,
      specific pools of biomarkers could possibly be selected as specific for toxin
      exposure.

PMID- 18063145
TI  - Malignant link between chronic heart failure and acute cardiac decompensation in
      patients with persistently increased serum concentrations of cardiac troponin.
AB  - During the progression of heart failure (HF), phases of chronic compensation and
      acute decompensation alternate and the clinical status worsens during the acute
      phase. At the present time, few studies have focused their attention on the
      cycles of compensated and decompensated phases from the perspective of myocyte
      injury. We hypothesize that persistently increased serum cTn concentrations
      during chronic compensated HF identify patients likely to need multiple
      admissions to the hospital for management of acute cardiac decompensation,
      worsening their long-term prognosis by causing further myocyte injury during the
      acute phase. In patients with acute cardiac decompensation, myocyte injury
      observed within hours or days has a long-term predictive value, and the acute
      surge of myocyte injury occurring in the acutely decompensated phase might be an
      important therapeutic target from the perspective of myocyte preservation.
      Clinical trials that limit myocyte injury during acutely decompensated as well as
      during chronic compensated HF are warranted.

PMID- 18063146
TI  - No added value of age at menopause and the lifetime cumulative number of
      menstrual cycles for cardiovascular risk prediction in postmenopausal women.
AB  - BACKGROUND: The aim of the present study was to investigate the added value of
      age at menopause and the lifetime cumulative number of menstrual cycles in
      cardiovascular risk prediction in postmenopausal women. METHODS: This study
      included 971 women. The ankle-arm index was used as a proxy for cardiovascular
      morbidity and mortality. The ankle-arm index was calculated for each leg by
      dividing the highest ankle systolic blood pressure by the highest brachial
      systolic blood pressure. A cut-off value of 0.95 was used to differentiate
      between low and high risk women. Three cardiovascular risk models were
      constructed. In the initial model all classical predictors for cardiovascular
      disease were investigated. This model was then extended by age at menopause or
      the lifetime cumulative number of menstrual cycles to test their added value for
      cardiovascular risk prediction. Differences in discriminative power between the
      models were investigated by comparing the area under the receiver operating
      characteristic (ROC) curves. RESULTS: The mean age was 66.0 (+/-5.6) years. The 6
      independent predictors for cardiovascular disease were age, systolic blood
      pressure, total to HDL cholesterol ratio, current smoking, glucose level, and
      body mass index > or =30 kg/m(2). The ROC area was 0.69 (0.64-0.73) and did not
      change when age at menopause or the lifetime cumulative number of menstrual
      cycles was added. CONCLUSIONS: The findings in this study among postmenopausal
      women did not support the view that age at menopause or a refined estimation of
      lifetime endogenous estrogen exposure would improve cardiovascular risk
      prediction as approximated by the ankle-arm index.

PMID- 18063147
TI  - Common community infections and the risk for coronary artery disease and acute
      myocardial infarction: evidence for chronic over-expression of tumor necrosis
      factor alpha and vascular cells adhesion molecule-1.
AB  - BACKGROUND: Although several common community infections have been associated
      with the risk for coronary artery disease (CAD), their role in the development of
      acute myocardial infarction (AMI) is still unclear. We examined the prevalence of
      IgG and IgM (or IgA) antibodies against common infections such as HSV, Hepatitis
      A (HAV), Helicobacter pylori (HP), cytomegalovirus (CMV) and Chlamydia pneumoniae
      (CP), in CAD and AMI patients, and their relationship with pro-atherogenic
      inflammatory molecules. METHODS: A total number of 337 subjects were included in
      this study: 150 patients with angiographically documented stable CAD, 138
      patients admitted with AMI and 49 healthy individuals. Serum IgG and IgM against
      HAV, CMV and HSV, IgG against HP and IgG/IgA against CP were determined in all
      participants. Serum tumor necrosis factor alpha (TNF-alpha) and soluble vascular
      cells adhesion molecule (sVCAM-1), were determined by ELISA. RESULTS: Patients
      with CAD were more likely to have anti-HAV IgG (94.4%), anti-HSV IgG (97.2%) and
      anti-HP IgG (55.1%) compared to healthy individuals (70.8%, 89.6% and 39.6%
      respectively, p<0.05 for all). In multivariate analysis, anti-HAV IgG was an
      independent predictor of CAD (beta(SE): 0.187(0.075), p=0.015). Among the CAD
      patients, the presence of anti-CP IgA was more frequent in those admitted with
      AMI (39%) compared to those with stable CAD (21%, p<0.05). Finally, both patients
      and controls had significantly higher levels of sVCAM-1 and TNF-alpha in the
      presence of anti-HAV IgG, compared to those without anti-HAV IgG (p<0.05 for
      all). CONCLUSION: Past infections with HAV, HSV and HP are associated with higher
      risk for coronary atherosclerosis, while the presence of anti-HAV IgG is also
      associated with higher levels of TNF-alpha and sVCAM-1. Furthermore, the presence
      of recent infection by CP is associated with higher risk for AMI among CAD
      patients. These findings are important since they demonstrate that past HAV, HSV
      and HP infections may affect cardiovascular risk, while recent CP infection may
      be implicated in the triggering of AMI among CAD patients.

PMID- 18063148
TI  - Sigmoid-shaped ventricular septum causing mid-ventricular obstruction: report of
      2 cases.
AB  - Sigmoid-shaped ventricular septum (SSVS) is frequently observed in elderly
      patients, but association of mid-ventricular obstruction is rare. In this report,
      we describe 2 patients with SSVS who had mid-ventricular obstruction and
      intracavity pressure gradient detected by echocardiography and cine magnetic
      resonance imaging. Attention should be paid to SSVS because it may cause
      clinically significant hemodynamic derangements related to mid-ventricular
      obstruction.

PMID- 18063149
TI  - Tako-tsubo cardiomyopathy complicated by apical thrombus formation: a case
      report.
AB  - Tako-tsubo cardiomyopathy is a rare, stress-related cardiomyopathy that occurs in
      postmenopausal women after emotional or physiological stressors. The prognosis is
      favorable with normalization of wall motion abnormalities within weeks. We report
      a rare case of tako-tsubo cardiomyopathy complicated by a left thrombus. Coronary
      angiography showed normal coronary arteries, although the echocardiography
      demonstrated the ballooning of the apex with hyperkinesis of the base in addition
      to a left ventricular thrombus. It is thought that this thrombus may have been
      caused by left ventricular dyskinesis. After short-term anticoagulant therapy,
      echocardiography revealed complete resolution of the left ventricular thrombus.

PMID- 18063150
TI  - Myocarditis in a patient with Duchenne muscular dystrophy detected by
      cardiovascular magnetic resonance and cardiac biopsy.

PMID- 18063151
TI  - Resistance of potential probiotic lactic acid bacteria and bifidobacteria of
      African and European origin to antimicrobials: determination and transferability
      of the resistance genes to other bacteria.
AB  - Probiotic bacteria and starter cultures of Lactobacillus, Weissella and
      Bifidobacterium of African and European origins were studied and compared for
      their susceptibility to antimicrobials. The study included, for all isolates,
      determination of MICs (Minimal Inhibitory Concentration) for 24 antimicrobials,
      detection of resistance genes by PCR reactions using specific primers and
      sequencing of positive amplicons. The ability of Lb. reuteri from Africa to
      transfer the erythromycin resistance gene erm(B) to closely related bacteria was
      investigated by conjugation. Variations were observed and high levels of
      intrinsic resistance were found among the tested species. Positive amplicons were
      obtained for resistance genes encoding aminoglycoside (aph(3')-III, aadA, aadE)
      and tetracycline (tet(S)) from isolates from Europe and macrolide (erm(B)) from
      an isolate from Africa. However, only the erm(B) gene found in Lb. reuteri L4:
      12002 from Africa contained a homologous sequence to previously published
      sequences. This gene could be transferred in vitro to enterococci. Higher
      prevalence of phenotypic resistance for aminoglycoside was found in isolates from
      Europe.

PMID- 18063155
TI  - Guidelines for the management of heart failure: differences in guideline
      perspectives.
AB  - The development of clinical or practice guidelines is thought to be a successful
      strategy for improving quality of care. Accordingly, many professional
      organizations, societies, institutions of health care or policy, and even
      countries have published practice guidelines on a variety of topics, including
      heart failure.

PMID- 18063154
TI  - Heart failure in the twenty-first century: is it a coronary artery disease or
      hypertension problem?
AB  - Hypertension and coronary disease are major risk factors for the incidence and
      progression of heart failure. These two risk factors frequently coexist, and have
      additive and synergistic effects that promote both left ventricular remodeling
      and heart failure in the general population. The relative contributions of these
      two risk factors to heart failure burden in the community may vary based on age,
      gender, and race. In general, attribution of heart failure in the community to
      solely one of these two risk factors is inappropriate. Prevention of both
      hypertension and coronary disease is important for preventing heart failure in
      the twenty-first century.

PMID- 18063156
TI  - Applying hypertension guidelines to reduce the burden of heart failure.
AB  - If the recommendations of Joint National Committee 7 are implemented, the
      incidence of heart failure should continue to decline. These recommendations are
      designed not only to reduce the incidence of heart failure but also prevent other
      target end-organ damage and reduce overall cardiovascular morbidity and
      mortality. The emphasis of these recommendations is to reduce systolic blood
      pressure, because the risk of mortality caused by heart disease and stroke
      doubles for every 20-mm Hg increase in systolic blood pressure. Practitioners are
      encouraged to use a combination of lifestyle changes and pharmacotherapy to
      achieve systolic blood pressure goals and consider the use of thiazide diuretics
      as first-line therapy to achieve the ultimate goal of reducing end-organ damage.

PMID- 18063157
TI  - Heart failure in the diabetic patient.
AB  - This review examines the extent of the increased rate of heart failure (HF) in
      the diabetic patient, along with the possible causes for this increase and the
      poor prognosis associated with HF. Also reviewed are the therapies that are
      available for the treatment of diabetic HF and whether intensifying the use of
      these therapies might improve the worsened clinical outcomes for the patient who
      has diabetes.

PMID- 18063158
TI  - Pharmacologic therapy for acute heart failure.
AB  - Acute heart failure syndrome (AHFS) is prevalent and costly, and clinical
      development of pharmacologic therapy remains challenging. Relieving congestion is
      still the central goal in the decompensated states, although the predominant
      approach remains the use of intravenous loop diuretics. Newer agents such as
      vasopressin receptor antagonists have yet to show incremental benefits. A
      resurgence of interest in vasodilator therapy has been supported by a better
      understanding of the pathophysiology of AHFS and the availability of nesiritide
      and other natriuretic peptides, but long-term clinical outcomes data are lacking
      and highly debated. Several promising drugs are currently undergoing clinical
      development for the treatment of AHFS, although many of the clinical challenges
      remain unresolved.

PMID- 18063159
TI  - Small pumps for ventricular assistance: progress in mechanical circulatory
      support.
AB  - Compared with earlier models, current pumps are much smaller, simpler, and more
      efficient, offering long-term or even permanent support. They fit a wider size
      range of patients and are less invasive to implant. Because they have few moving
      parts, they are less susceptible to infection and failure. Additionally, they
      offer much greater patient comfort, allowing a relatively normal lifestyle. This
      article focuses on the current state of continuous-flow pumps for both temporary
      and long-term use in treating acute and chronic heart failure.

PMID- 18063160
TI  - Invasive hemodynamic monitoring the aftermath of the ESCAPE trial.
AB  - The Swan-Ganz catheter was developed 35 to 40 years ago for intensive and cardiac
      care units to allow bedside placement and continuous monitoring and recording of
      right-sided heart, pulmonary artery, and wedge pressures and reasonably accurate
      determinations of cardiac output. Considerations for the clinical application of
      this balloon-tip, flow-directed, multilumen, thermodilution pulmonary artery
      catheter in the post-ESCAPE era are presented.

PMID- 18063161
TI  - Anti-angiotensin therapy: new perspectives.
AB  - Activation of the renin-angiotensin system (RAS) plays an important role in the
      pathogenesis of heart failure. Thus, strategies for the treatment of heart
      failure have focused on agents that block the RAS. More recently, the role of
      angiotensin receptor blockers (ARBs) in heart failure therapy has been better
      defined. This article examines the rationale and role of ARBs in the treatment of
      patients with heart failure on the basis of evidence from clinical trials.

PMID- 18063162
TI  - Beta blockers or angiotensin-converting-enzyme inhibitor/angiotensin receptor
      blocker: what should be first?
AB  - The historical choice of angiotensin-converting enzyme (ACE) inhibition as first
      line therapy in heart failure is challenged by early activation of the
      sympathetic system and multiple ways beta blockade (in particular, unselective
      agents such as carvedilol) may affect cardiac remodeling, its underlying
      mechanisms, and, hence, progression of heart failure, compared with ACE
      inhibition. Existing comparisons indicate similar or possible greater efficacy of
      beta blockade than ACE inhibition. As beta blockade is well tolerated, it could
      be considered in individual stable patients. However, early combined treatment
      with both neurohormonal antagonists remains preferable to either neurohormonal
      antagonist alone and should not be delayed.

PMID- 18063163
TI  - Biventricular pacing and defibrillator use in chronic heart failure.
AB  - Since the 1970s when the implantable cardioverter defibrillator (ICD) was
      developed, multiple clinical trials have documented survival benefits in certain
      high-risk subsets of heart failure patients. Over the past decade, cardiac
      resynchronization therapy (CRT) emerged as an important therapy in carefully
      selected patients with ongoing symptoms despite optimized pharmacological
      therapy. ICDs should be considered first-line therapy for survivors of life
      threatening ventricular arrhythmic events. Subsets of patients with both ischemic
      and nonischemic dilated cardiomyopathy appear to have a survival benefit from
      primary ICD therapy. CRT has resulted in substantial symptomatic improvement and
      survival benefits in a subgroup of chronic heart failure patients. CRT should be
      considered in heart failure patients undergoing ICD implantation who have
      evidence of ventricular dyssynchrony.

PMID- 18063164
TI  - Phylogenetic analysis of the NS5 gene of dengue viruses isolated in Ecuador.
AB  - Dengue virus (DENV) is a member of the genus Flavivirus of the family
      Flaviviridae. DENV causes a wide range of diseases in humans, from the acute
      febrile illness dengue fever (DF) to life-threatening dengue hemorrhagic
      fever/dengue shock syndrome (DHF/DSS). There is not knowledge of the genetic
      relations among DENV circulating in Ecuador. Given the emerging behaviour of
      DENV, a single tube RT-PCR assay using a pair of consensus primers to target the
      NS5 coding region has been recently validated for rapid detection of
      flaviviruses. In order to gain insight into the degree of genetic variation of
      DENV strains isolated in Ecuador, DENV NS5 sequences from 23 patients were
      obtained by direct sequencing of PCR fragments using the mentioned one step RT
      PCR assay. Phylogenetic analysis carried out using the 23 Ecuadorian DENV NS5
      sequences, as well as 56 comparable sequences from DENV strains isolated
      elsewhere, revealed a close genetic relation among Ecuadorian strains and DENV
      isolates of Caribbean origin. The use of partial NS5 gene sequences may represent
      a useful alternative for a rapid phylogenetic analysis of DENV outbreaks.

PMID- 18063166
TI  - Medical literature ahead: proceed with caution.

PMID- 18063165
TI  - Efficient expression of vascular endothelial growth factor using minicircle DNA
      for angiogenic gene therapy.
AB  - The application of plasmid DNA (pDNA)-based gene therapy is limited by its
      inefficient transgene expression. In this study, minicircle DNA was evaluated for
      efficient vascular endothelial growth factor (VEGF) expression in skeletal muscle
      cells. Production of minicircle DNA encoding VEGF was studied by a semi
      quantitative electrophoresis method leading to optimized bacterial culture
      conditions and producing high purity (86.6%) minicircle DNA. The VEGF minicircle
      DNA under control of the SV40 promoter (pMini-SV-VEGF) showed an increased amount
      of VEGF mRNA and up to 8 times more VEGF expression than a conventional plasmid
      (pSV-VEGF) in two different skeletal muscle cell lines (C2C12 and L8). Minicircle
      DNA with different promoters, including the SV40, CMV and chicken beta-actin, was
      tested for VEGF expression in a C2C12 skeletal muscle cell line. The high VEGF
      expression generated by minicircle DNA stimulated efficient endothelial cell
      growth in vitro. Furthermore, minicircle DNA expressed higher VEGF compared to
      conventional plasmid in the tibialis anterior (TA) muscle of mice. Taken
      together, the results suggest that minicircle DNA is an efficacious gene vector
      for angiogenic VEGF expression in skeletal muscle and may be useful for treating
      peripheral arterial disease (PAD).

PMID- 18063167
TI  - Arthroscopic versus open osteoplasty of the head-neck junction: a cadaveric
      investigation.
AB  - PURPOSE: Femoroacetabular impingement can be successfully treated by open
      osteoplasty, although arthroscopic osteoplasty is growing in popularity. We
      compared the precision and accuracy of arthroscopic versus open osteoplasty.
      METHODS: We randomly assigned 8 paired fresh-frozen cadaveric pelvises to an open
      or arthroscopic technique and performed osteoplasty on both anterior femoral head
      neck junctions. We calculated the volume and location of the resected bone using
      digital subtraction of preoperative and postoperative computed tomography.
      RESULTS: Statistical analysis showed no differences between the techniques
      regarding volume, depth, or overall arc of resection. The arthroscopic group was
      closer to the predetermined starting point, and the open group was closer to the
      end-point. CONCLUSIONS: This study confirms the ability to perform arthroscopic
      decompressions of the head-neck junction for isolated cam-type impingement with
      accuracy and precision that approach those of the open surgical technique.
      CLINICAL RELEVANCE: This report gives important information on the accuracy and
      precision of arthroscopic osteoplasty of the femoral head-neck junction as a
      feasible alternative to open resection.

PMID- 18063168
TI  - Single-row suture anchor repair of the rotator cuff is biomechanically equivalent
      to double-row repair in a bovine model.
AB  - PURPOSE: The purpose of this study was to determine biomechanical differences in
      cyclic elongation and ultimate strength between double-row rotator cuff repair
      and single-row repair for partial rotator cuff repairs. METHODS: We randomly
      assigned 18 immature bovine specimens (aged 12 to 16 weeks) to 3 repair groups (6
      per group). A 1 x 2-cm defect was created at the infraspinatus tendon insertion
      site. Two suture anchors were implanted 1 cm apart at the anatomic insertion area
      for the lateral row. Two suture anchors were implanted 1 cm medial to the lateral
      row and 1 cm apart from each other for the medial row. Repair groups were
      constructed as follows: single-row repair with double-loaded suture anchors
      (group 1), double-row repair with single-loaded medial row and double-loaded
      lateral row (group 2), and double-row repair with single-loaded medial row and
      single-loaded lateral row (group 3). Specimens were cyclically loaded from 10 N
      to 90 N for 500 cycles and then loaded at 0.5 mm/s to failure. Data for cyclic
      elongation, with loads at 3 mm, 5 mm, and 10 mm, were analyzed via a 1-way
      analysis of variance (P < .05). RESULTS: There were no significant differences
      for peak elongation after cyclic loading between groups. There were no
      significant differences between repair groups for loads at 3 mm, 5 mm, and 10 mm
      of elongation. Constructs typically failed by knot slippage (83%), with a single
      sample having tendon-suture failure (17%). CONCLUSIONS: Double-row repair did not
      show a biomechanical advantage compared with single-row repair. With this result
      in mind, the theoretic advantage of a potentially larger footprint must be
      balanced against the added surgical time, complexity, and cost of double-row
      repair. CLINICAL RELEVANCE: Arthroscopic surgeons should choose the best form of
      fixation for a given patient, without undue emphasis on single-row repair versus
      double-row repair. The clinical and biologic impact of footprint restoration was
      not addressed in this study.

PMID- 18063169
TI  - Arthroscopic perspective of the axillary nerve in relation to the glenoid and arm
      position: a cadaveric study.
AB  - PURPOSE: The purposes of this study were to examine the morphologic features of
      the axillary nerve and its relation to the glenoid under an arthroscopic setup,
      and to determine the changes in nerve position according to different arm
      positions. METHODS: Twenty-three fresh-frozen fore-quarter cadaveric shoulder
      specimens were used for evaluations in an arthroscopic setup with the lateral
      decubitus position. The main trunk of the axillary nerve with or without some of
      its branches was exposed after careful arthroscopic dissection. Morphologic
      features and the course of the axillary nerve from the anterior and posterior
      portals were documented. The closest distances from the glenoid rim were measured
      with a probe by use of a distance range system. The changes in nerve position
      were determined in 4 different arm positions. At the end of arthroscopic
      examination, the nerves were marked and verified by open dissections. RESULTS:
      The axillary nerve appeared in the joint near the inferior edge of the
      subscapularis muscle. With reference to the inferior glenoid rim horizontally,
      the nerve had a mean running angle of 23 degrees (range, 14 degrees to 41
      degrees; SD, 8 degrees ). The closest points from the glenoid were between the
      5:30- and 6:00-o'clock position (right) or 6:00- and 6:30-o'clock position
      (left). The closest distance range varied from 10 to 25 mm in the neutral arm
      position. The abduction-neutral position resulted in the greatest distance
      between the inferior glenoid and the nerve. CONCLUSIONS: The abduction-neutral
      rotation position was the optimal position for minimizing axillary nerve
      injuries, because it resulted in the greatest distance between the inferior
      glenoid and the nerve. CLINICAL RELEVANCE: Knowledge of the anatomy of the
      axillary nerve aids the shoulder surgeon in avoiding nerve injury during
      arthroscopic procedures. Abduction-neutral rotation may be more helpful for
      arthroscopic surgeons performing procedures in the anteroinferior glenoid with
      the nerve being farther away from the working field.

PMID- 18063170
TI  - Arthroscopic distal clavicle resection: a biomechanical analysis of resection
      length and joint compliance in a cadaveric model.
AB  - PURPOSE: The purposes of this study were to assess the effects of a distal
      clavicle resection of less than 5 mm on bony contact and compliance in the
      acromioclavicular (AC) joint and to localize areas of persistent contact in the
      AC joint. The hypothesis of this study was that AC contact can be avoided by
      excising less than 5 mm of bone from the distal clavicle. METHODS: Ten human AC
      joints underwent compressive loading of the distal clavicle into the acromion
      after the following: disk excision, distal clavicle resection of 2.5 mm, and
      distal clavicle resection of 5 mm. The joint resistance force, stiffness, and
      presence and location of contact were monitored. RESULTS: Excising 2.5 mm or less
      resulted in no bone-to-bone abutment in 6 of 10 specimens. A 5-mm resection
      resulted in successful decompression in all specimens. The specimens that
      required a 5-mm resection had minimal contact after the 2.5-mm resection
      (inferior-posterior quadrant only). AC joint stiffness decreased significantly
      with increasing amounts of clavicular resection (P = .01). CONCLUSIONS: A 5-mm
      distal clavicle resection guaranteed no abutment but decreased joint stiffness.
      Persistent contact occurred only in the inferior-posterior quadrant of the joint
      after a 2.5-mm resection. CLINICAL RELEVANCE: These findings support the efficacy
      of a 5-mm distal clavicle resection for eliminating bony contact but suggest that
      there is a bony contribution to AC joint stiffness. A resection of 2.5 to 5.0 mm
      could be adequate if care is taken to excise a greater depth of bone in the
      inferior-posterior quadrant.

PMID- 18063171
TI  - Hip arthroscopy after previous surgical hip dislocation for femoroacetabular
      impingement.
AB  - PURPOSE: The purpose of this study was to examine whether arthroscopic
      adhesiolysis can relieve symptoms of patients with persistent pain after open
      surgical hip dislocation for femoroacetabular impingement syndrome without
      osseous or cartilaginous alterations. METHODS: This study comprised 16
      consecutive patients (6 men and 10 women; mean age, 33.5 years [range, 19 to 60
      years]) with persistent pain without osseous or cartilaginous alterations after
      surgical hip dislocation for the treatment of femoroacetabular impingement. At
      index surgery, all patients had osteochondroplasty of the head-neck junction and
      resection of the acetabular rim with reattachment of the labrum in 9 cases. All
      patients had preoperative magnetic resonance imaging-arthrogram and were treated
      with arthroscopy of the hip. RESULTS: At arthroscopy, all reattached labra were
      stable. In the cases without preservation of the labrum at the index operation,
      the joint capsule was attached at the level of the acetabular rim and synovitis
      was noticed. All patients had adhesions between the neck of the femur and joint
      capsule or between the labrum and capsule. In 3 patients the arthroscopic
      procedure was technically limited by massive thickening of the capsule. Overall,
      81% of patients (13/16) showed less pain or were pain-free. The Merle d'Aubigne
      score improved from 13 points preoperatively to 16 points at the last follow-up.
      CONCLUSIONS: Persistent pain after surgical dislocation of the hip without
      evidence of cartilaginous and osseous alterations could result from intra
      articular adhesions. Hip arthroscopy after previous surgery can be demanding
      because of scarring. If the adhesions can be released, good results can be
      achieved. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 18063172
TI  - Usefulness of radial contrast-enhanced computed tomography for the diagnosis of
      acetabular labrum injury.
AB  - PURPOSE: The purpose of this study was to evaluate the usefulness of radial
      contrast-enhanced computed tomography (CT) in the diagnosis of acetabular labrum
      injury. METHODS: We studied 21 hip joints in 21 patients (8 joints in 8 male
      patients and 13 joints in 13 female patients), aged between 16 and 81 years
      (mean, 43 years) at examination, who underwent both radial contrast-enhanced CT
      and hip arthroscopy. Plain radiography showed no abnormalities in the bone and
      joint in 19 joints and acetabular dysplasia in 2 joints. When we performed radial
      contrast-enhanced CT, a mixture of 5 mL of 2% lidocaine chloride and 10 mL of 64%
      iotrolan was injected intra-articularly under x-ray fluoroscopy. CT was conducted
      with a 4-slice multidetector CT system operated at a voltage of 120 kilovolt
      peak, current of 300 mA, collimation beam of 2 mm, field of view of 320 mm, slice
      thickness of 0.5 mm, table speed of 44 mm/s, and helical pitch of 5.5. Images
      were reconstructed by computer software for radial slices at 15 degrees intervals
      perpendicular to the labral rim. The mean interval between the CT scan and
      arthroscopy was 13.2 days. RESULTS: By contrast-enhanced CT, acetabular labrum
      tears were observed in 12 joints, loss of acetabular labrum was found in 1 joint,
      and no abnormalities were present in 8 joints. By arthroscopy, acetabular labrum
      tears were observed in 13 joints, loss of acetabular labrum was found in 1 joint,
      and no abnormalities were present in 7 joints. When the results of the 2 methods
      were compared, 12 joints had true-positive findings, 8 joints had true-negative
      findings, and 1 joint had a false-negative finding. Therefore contrast-enhanced
      CT had a sensitivity of 92.3%, specificity of 100%, and accuracy of 95.2%.
      CONCLUSIONS: The sensitivity, specificity, and accuracy of radial contrast
      enhanced CT for the diagnosis of acetabular labrum injury are 92.3%, 100%, and
      95.2%, respectively. We recommend radial contrast-enhanced CT for the diagnosis
      of acetabular labrum injury in patients in whom magnetic resonance imaging is
      contraindicated. LEVEL OF EVIDENCE: Level IV, diagnostic study.

PMID- 18063173
TI  - Radiologic and intraoperative findings in revision hip arthroscopy.
AB  - PURPOSE: The purpose of this study was to identify possible causes of failure of
      hip arthroscopy by reviewing the intraoperative and radiologic findings in a
      series of patients requiring revision hip arthroscopy. METHODS: We
      retrospectively reviewed 24 revision hip arthroscopy cases performed in 23
      patients (14 female and 9 male; mean age, 33.6 years; 1 bilateral). The review
      included indications for surgery, intraoperative findings, and arthroscopic
      interventions for both the primary and revision surgeries. Imaging studies,
      including radiography, magnetic resonance imaging, and 3-dimensionally
      reconstructed computed tomography scans, were analyzed for the presence of
      preoperative bony impingement lesions (e.g., femoral head-neck junction "cam"
      lesions or anterosuperior acetabular "pincer" lesions). RESULTS: The mean
      interval between previous hip arthroscopy and recurrence of symptoms was 6.1
      months. In 13 of 24 cases (54%), patients had no significant improvement at any
      point after the primary hip arthroscopy. The mean interval between the previous
      hip arthroscopy and revision surgery was 25.6 months. Unaddressed or undertreated
      bony impingement lesions were found in 19 of 24 cases (79%) and were identified
      on imaging studies before revision hip arthroscopy. A tight psoas tendon and
      corresponding labral impingement lesion were identified by arthroscopic
      visualization in 7 of 24 cases, for which partial psoas tendon release was
      performed. Eight cases of failed labral repair were addressed with labral
      debridement and removal of suture material. Of these 8 cases, 6 also had bony
      impingement, which was also addressed at the time of the revision surgery.
      CONCLUSIONS: Failure to address bony impingement lesions of the hip and a tight
      psoas tendon are key factors in unsuccessful hip arthroscopy and may require
      revision surgery. Furthermore, failure of labral repairs may be the result of
      unrecognized bony impingement at the time of initial surgery. LEVEL OF EVIDENCE:
      Level IV, prognostic case series.

PMID- 18063174
TI  - The relationship between the MPP test and arthroscopically found medial patellar
      plica pathology.
AB  - PURPOSE: This study investigated whether the mediopatellar plica (MPP) test
      developed by the authors could be used preoperatively to predict MPP pathology
      found at arthroscopy. METHODS: Between January 1999 and August 2004, 65 patients
      (66 knees, group I) with anteromedial knee pain were examined using the MPP test
      before undergoing an arthroscopic procedure. In the control group, 101 patients
      (106 knees, group II) with lateral tibiofemoral joint line pain were examined by
      the MPP test. After arthroscopic excision of a thickened MPP, the visual analogue
      scale and the Lysholm scoring scale were recorded during follow-up. RESULTS: Of
      the 172 knees evaluated, the sensitivity, specificity, and positive and negative
      predictive value for the MPP test were 89.5%, 88.7%, 78.7%, and 94.4%,
      respectively. The accuracy value was 89.0%. Thirteen knees (7.6%) were
      categorized as false positives, 7 knees had fat pad synovial fringe entrapments,
      5 knees had localized synovitis, and 1 knee had a focal cartilage lesion on the
      medial femoral condyle. In 53 knees diagnosed with pathologic MPP entrapment in
      group I, the mean postoperative VAS was 1.3 (range, 0 to 4) and the mean
      postoperative Lysholm score was 91.4 (range, 74 to 100), while all knees showed a
      negative MPP test after the mean follow-up of 48.1 months (range, 24 to 96
      months). CONCLUSIONS: The MPP test is reliable to predict the pathologic MPP
      entrapment, and arthroscopic excision of pathologic MPP shows satisfactory
      clinical results. LEVEL OF EVIDENCE: Level III, diagnostic study of
      nonconsecutive patients without consistently applied gold standard.

PMID- 18063175
TI  - The influence of femoral technique for graft placement on anterior cruciate
      ligament reconstruction using a skeletally immature canine model with a rapidly
      growing physis.
AB  - PURPOSE: The purpose of this study was to evaluate 3 different femoral techniques
      of anterior cruciate ligament (ACL) reconstruction using a skeletally immature
      canine model. METHODS: A soft-tissue autograft ACL reconstruction was performed
      in 25 ten-week-old canines via a central transphyseal tibial tunnel and 1 of 3
      femoral techniques: epiphyseal, over the top, or transphyseal. The contralateral
      hind limbs served as controls. The canines were killed at 16 weeks
      postoperatively and evaluated by gross inspection, plain radiographs,
      photography, magnetic resonance imaging, and histomorphometry. RESULTS: There
      were no significant differences in femoral longitudinal growth; however, tibial
      growth was significantly greater on the experimental side relative to controls (P
      = .001). Angular and rotational deformities were noted on the femoral side but
      not on the tibial side. The epiphyseal technique resulted in less angular
      deformity and most closely maintained the anatomic position of the ACL graft with
      growth; however, this technique exhibited increased femoral rotational deformity.
      All techniques exhibited a high rate of graft failure. Magnetic resonance imaging
      revealed chondral and subchondral injuries to the lateral femoral condyle, most
      frequently in the epiphyseal group. CONCLUSIONS: From the results of our study,
      we cannot advocate any single femoral reconstructive technique. An epiphyseal
      femoral technique may reduce the risk of angular deformity and allow a more
      optimal femoral graft position after growth as opposed to transphyseal and over
      the-top techniques. However, the epiphyseal technique may possess an increased
      risk for rotational deformity, physeal injury, and articular surface injury.
      Metaphyseal fixation of ACL grafts traversing rapidly growing physes may be
      responsible for the observed abnormalities in graft integrity, femoral graft
      position, and femoral angulation and rotation. CLINICAL RELEVANCE: ACL
      reconstruction in the skeletally immature individual is complicated by the
      presence of active physeal and epiphyseal cartilage surrounding the growing knee,
      the pathophysiologic consequences of injury to these developing structures, and
      the final effect on the anatomy and function of the graft, bone, and articular
      surface. Animal models can provide insight and direction as we develop and
      evaluate our treatment methods for this clinical problem, but these animal models
      have anatomic and physiologic differences that limit direct comparison to humans.

PMID- 18063176
TI  - A meta-analysis of the incidence of anterior cruciate ligament tears as a
      function of gender, sport, and a knee injury-reduction regimen.
AB  - PURPOSE: The literature has shown that anterior cruciate ligament (ACL) tear
      rates vary by gender, by sport, and in response to injury-reduction training
      programs. However, there is no consensus as to the magnitudes of these tear rates
      or their variations as a function of these variables. For example, the female
      male ACL tear ratio has been reported to be as high as 9:1. Our purpose was to
      apply meta-analysis to the entire applicable literature to generate accurate
      estimates of the true incidences of ACL tear as a function of gender, sport, and
      injury-reduction training. METHODS: A PubMed literature search was done to
      identify all studies dealing with ACL tear incidence. Bibliographic cross
      referencing was done to identify additional articles. Meta-analytic principles
      were applied to generate ACL incidences as a function of gender, sport, and prior
      injury-reduction training. RESULTS: Female-male ACL tear incidences ratios were
      as follows: basketball, 3.5; soccer, 2.67; lacrosse, 1.18; and Alpine skiing,
      1.0. The collegiate soccer tear rate was 0.32 for female subjects and 0.12 for
      male subjects. For basketball, the rates were 0.29 and 0.08, respectively. The
      rate for recreational Alpine skiers was 0.63, and that for experts was 0.03, with
      no gender variance. The two volleyball studies had no ACL tears. Training reduced
      the ACL tear incidence in soccer by 0.24 but did not reduce it at all in
      basketball. CONCLUSIONS: Female subjects had a roughly 3 times greater incidence
      of ACL tears in soccer and basketball versus male subjects. Injury-reduction
      programs were effective for soccer but not basketball. Recreational Alpine skiers
      had the highest incidences of ACL tear, whereas expert Alpine skiers had the
      lowest incidences. Volleyball may in fact be a low-risk sport rather than a high
      risk sport. Alpine skiers and lacrosse players had no gender difference for ACL
      tear rate. Year-round female athletes who play soccer and basketball have an ACL
      tear rate of approximately 5%. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 18063177
TI  - Does the position of the femoral tunnel affect the laxity or clinical outcome of
      the anterior cruciate ligament-reconstructed knee? A clinical, prospective,
      randomized, double-blind study.
AB  - PURPOSE: The aim of this study was to evaluate whether a change in the femoral
      graft insertion site between the 1-o'clock (high) and 2-o'clock (low) positions
      could change the laxity, the score on the 2000 International Knee Documentation
      Committee (IKDC) Knee Examination Form, or the score on the 2000 subjective IKDC
      Knee Evaluation Form in the anterior cruciate ligament (ACL)-reconstructed knee.
      METHODS: The study was designed as a prospective, randomized, double-blind
      investigation. We randomized 30 patients to the low tunnel position group and 30
      to the high tunnel position group. Four-stranded semitendinosus and gracilis
      single-bundle grafts were used. At follow-up, the patients were examined
      according to the IKDC evaluation form and the IKDC examination form. The exact
      measurements of laxity at 25 degrees and 70 degrees were performed by use of the
      Rolimeter (Aircast, Boca Raton, FL). Standardized radiographs were evaluated.
      RESULTS: In total, 26 patients in the low tunnel position group and 25 in the
      high tunnel position group completed the study. At follow-up, we found no
      significant difference in the laxity at 25 degrees and 70 degrees or scores on
      the IKDC examination form. We found a significant difference in the scores on the
      IKDC evaluation form, favoring the low position, with a subjective score of 82.8
      versus 70.4. CONCLUSIONS: A change in the femoral tunnel placement from 1 o'clock
      to 2 o'clock did not result in a detectable change in the sagittal laxity at 25
      degrees and 70 degrees , on the pivot-shift test, or on the IKDC examination form
      scores. However, we found a significant difference between the two groups in the
      scores on the IKDC evaluation form, most evident in the subgroups dealing with
      the patient's subjective knee stability. We conclude that it is possible to
      improve the clinical result in 1-bundle ACL reconstruction by lowering the tibial
      tunnel angle and thereby lowering the femoral tunnel toward the 2-o'clock
      position. LEVEL OF EVIDENCE: Level I, therapeutic prospective randomized trial.

PMID- 18063178
TI  - Do broken cross-pins compromise stability after anterior cruciate ligament
      reconstructions with hamstring tendons?
AB  - PURPOSE: The purpose of this prospective study was to define the relation between
      the integrity of cross-pin femoral fixation and stability after anterior cruciate
      ligament (ACL) reconstructions. METHODS: Thirty-one consecutive ACL
      reconstructions were performed with hamstring tendons fixed with bioabsorbable
      cross-pin femoral fixation. All patients underwent magnetic resonance imaging at
      6 months postoperatively to assess the status of the cross-pin fixation. Clinical
      evaluations were performed via the Lachman and pivot-shift tests. The side-to
      side differences were measured by KT-1000 testing (MEDmetric, San Diego, CA) at 2
      years postoperatively. The patients were divided into 2 groups according to the
      status of the cross-pin. Group I consisted of those in whom the cross-pins were
      intact, and group II had broken cross-pins. RESULTS: There were 19 patients in
      group I and 12 (38.7%) in group II. Among the 24 cross-pins used in the 12
      patients in group II, 18 were broken. Among the patients in group I, the tip of
      the cross-pin was inside the posterior cortex of the distal femur in 7 (36.8%)
      and outside in 12 (63.2%). In group II the tip of the cross-pin was outside the
      posterior cortex of the distal femur in all patients. This number was
      significantly higher than that in group I (P = .017). Group I had significantly
      lower KT-1000 measurements than group II (P = .003). The mean KT-1000 side-to
      side difference was 0.47 mm in group I and 3.0 mm in group II. The Lachman and
      pivot-shift test data revealed no significant differences between the 2 groups (P
      = .467 and P = .796, respectively). CONCLUSIONS: This study showed that breakage
      of bioabsorbable cross-pins is a relatively common phenomenon. Broken cross-pins
      were a factor relating to laxity after ACL reconstructions with hamstring grafts.
      Posterior direction of the cross-pin may be a cause of pin breakage. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 18063179
TI  - A prospective magnetic resonance imaging study of the incidence of posterolateral
      and multiple ligament injuries in acute knee injuries presenting with a
      hemarthrosis.
AB  - PURPOSE: The purpose of this study was to determine whether the incidence of
      posterolateral knee injuries, as well as other concurrent knee ligament injuries,
      could be obtained from a prospective evaluation of magnetic resonance imaging
      scans in patients with an acute knee injury with a hemarthrosis. METHODS: We
      prospectively documented all patients with acute (within 30 days) knee injuries
      with a hemarthrosis over a 90-day period who underwent 1.5-T magnetic resonance
      imaging at a large referral imaging facility with 6 sites, effectively covering a
      large metropolitan area. The anterior cruciate ligament, superficial medial
      collateral ligament, and posterior cruciate ligament (PCL) and the following
      individual structures of the posterolateral corner were evaluated for high-grade
      injury: fibular collateral ligament, popliteus tendon, and popliteofibular
      ligament. RESULTS: Out of 331 consecutive acute knee injuries with a
      hemarthrosis, 265 ligament injuries occurred in 187 patients (56%). Of these 187
      patients with ligament injuries, 126 had isolated ligament injuries and 61 (33%)
      had combined multiple ligament injuries. Of the 187 patients with knee ligament
      injuries, 83 (44%) had isolated anterior cruciate ligament tears, 28 (15%) had
      isolated superficial medial collateral ligament tears, 11 (5%) had isolated PCL
      tears, and 4 (2.1%) had isolated posterolateral knee tears. Of the patients with
      posterolateral knee structure injuries, 87% (26/30) had multiple ligament
      injuries, with the overall incidence of posterolateral knee injuries among all
      knee ligament injuries being 16% and among all acute knee injuries with a
      hemarthrosis being 9.1%. Of the 27 patients with PCL tears, 16 (52%) had combined
      multiple ligament injuries. CONCLUSIONS: This study shows that in this
      population, the incidence of posterolateral knee injuries in patients with acute
      knee ligament injuries with a hemarthrosis was 9.1%. It also verified that most
      PCL and posterolateral corner injuries occur in combination with other ligament
      injuries. LEVEL OF EVIDENCE: Level II, development of diagnostic criteria on the
      basis of consecutive patients with a universally applied gold standard.

PMID- 18063180
TI  - Beginning hip arthroscopy: indications, positioning, portals, basic techniques,
      and complications.
AB  - Hip arthroscopy is becoming increasingly popular for the diagnosis and treatment
      of hip pathology, and the indications continue to evolve. The two most common
      approaches are the supine and lateral decubitus position. Both approaches can be
      performed effectively; however, each approach has its own benefits and drawbacks.
      In this review we will describe the indications for hip arthroscopy, the pros and
      cons of each approach, and the necessary equipment, portals, portal placement,
      commercially available distraction devices, and complications.

PMID- 18063181
TI  - Hybrid anterior cruciate ligament reconstruction: introduction of a new technique
      for anatomic anterior cruciate ligament reconstruction.
AB  - Recently, anatomic or double-bundle reconstruction of the anterior cruciate
      ligament (ACL) has been presented in an effort to more accurately restore the
      native anatomy. These techniques create 2 tunnels in both the femur and tibia to
      reproduce the bundles of the ACL. However, the increased number of tunnels,
      particularly on the femoral side, has raised some concerns among authors and
      surgeons. We describe a technique to reconstruct the 2 distinct bundles of the
      ACL by using a single femoral tunnel and 2 tibial tunnels, the "hybrid" ACL
      reconstruction. The femoral tunnel is drilled through an anteromedial arthroscopy
      portal, which allows placement in a more anatomic position. Fixation in the femur
      is achieved with a novel device that separates a soft-tissue graft into 2
      independently functioning bundles. Once fixed in the femur, the anteromedial and
      posterolateral bundles of the graft are passed through respective tunnels at the
      anatomic footprint on the tibia. These bundles are independently tensioned, which
      creates a reconconstruction that is similar to the native ACL. The technique
      presented provides surgeons with an alternative to other double-bundle techniques
      involving 4 tunnels.

PMID- 18063182
TI  - Arthroscopic tibial inlay for posterior cruciate ligament reconstruction.
AB  - The treatment of posterior cruciate ligament injuries remains controversial.
      There is no consensus on the ideal technique for reconstruction or the optimal
      graft design. Specifically, there is intense debate about which technique is
      superior: the open tibial inlay technique or the transtibial arthroscopic
      technique. We present a novel all-arthroscopic tibial inlay technique using a
      bifid bone-patellar tendon-bone allograft. This technique offers the advantages
      of the open tibial inlay technique, including avoidance of the killer turn and
      restoration of biomechanical stability. Furthermore, this technique is completely
      arthroscopic and therefore avoids the morbidity of the open tibial inlay
      technique from the posterior incision and capsulotomy. Our technique also avoids
      the need for repositioning of the patient intraoperatively. Our technique
      recreates the double-bundle anatomy of the posterior cruciate ligament and
      provides bony fixation on both tibial and femoral sides. Our cadaveric studies
      have shown that our technique restores stability as effectively as the
      traditional open tibial inlay technique. Early results in our first 11 cases are
      promising.

PMID- 18063183
TI  - A novel technique of all-inside arthroscopic triangular fibrocartilage complex
      repair.
AB  - Peripheral triangular fibrocartilage complex (TFCC) tears are amenable to repair.
      Limitations of current repair techniques include prolonged recovery and button or
      knot intolerance. We present a novel technique of an all-inside repair using
      existing technology (FasT-Fix; Smith & Nephew Endoscopy, Andover, MA) to
      circumvent these complications. This technique is faster, easily performed, safe,
      and potentially stronger than current repairs. Earlier motion and rehabilitation
      are instituted after this repair. The tear is debrided to stimulate angiogenesis.
      The FasT-Fix is inserted through the 3-4 portal with the arthroscope in the 6R
      portal. The first poly-L-lactic acid block is deposited peripheral to the tear.
      Upon penetration of the wrist capsule, a distinct decrease in resistance is felt.
      The introducer is withdrawn, depositing the block outside the capsule. The
      trigger on the introducer advances the second block into the deployment position.
      It is advanced and deposited central to the tear, forming a vertical mattress
      configuration. The introducer is removed, leaving the pre-tied suture. The knot
      is tightened and cut by use of the knot pusher/cutter. Multiple implants may be
      inserted to complete the repair. Postoperative care involves a sugartong splint
      for 2 weeks followed by a short arm cast for 4 weeks. Range of motion is begun
      thereafter with strengthening started at 10 weeks.

PMID- 18063184
TI  - Over-pointing technique: an approach to past-pointing arthroscopic knots on
      alternating suture posts without alternating the knot pusher.
AB  - As arthroscopic reconstructive surgery evolves, new techniques that improve
      operative efficiency while maintaining proven technical principles will enhance a
      surgeon's skill repertoire. A secure arthroscopic knot requires placing a series
      of reversed half-hitches on alternating posts and has traditionally involved
      alternating the knot-passing device between suture limbs to "past-point" each
      half-hitch, ensuring overall knot security. To increase the speed of knot-tying,
      a technical variation of keeping the knot pusher on the same suture limb
      throughout the knot-tying process, while still alternating posts, can be used.
      This technique involves alternately "pushing" and "pulling" sequential half
      hitches into place. It is important to note that although conventional past
      pointing is performed when "pulling" a half-hitch, it cannot be performed when
      purely "pushing" a half-hitch. In this article we describe a novel technique of
      "over-pointing" to be performed when pushing half-hitches into place. This is
      meant to be a complement to past-pointing by use of the knot pusher to advance
      the half-hitch and tighten the knot by over-riding the knot, effectively
      providing the equivalent of past-pointing by "pulling" the knot tight. In this
      way, a knot can be constructed without removing the device from the initial post
      strand of suture, saving time while maintaining the principles of secure knot
      tying.

PMID- 18063185
TI  - Heterotopic ossification after minimally invasive rotator cuff repair.
AB  - Heterotopic ossification is a common phenomenon after spinal cord injury, head
      injury, neurologic disorders, burns and other trauma, and joint arthroplasty.
      Periarticular ossifications after shoulder surgery have been known to occur since
      the 19th century, at an incidence of up to 27%. After arthroscopic and minimally
      invasive shoulder surgical procedures were introduced and came into broad use,
      reports about heterotopic ossification became very rare. We describe here a case
      of heterotopic bone formation in the subdeltoid fascia after arthroscopic
      subacromial decompression, acromioclavicular joint resection, and mini-open
      rotator cuff reconstruction were performed with 2 absorbable suture anchors 3
      months postoperatively. Computed tomography (CT) confirmed a massive heterotopic
      ossification of the deltoid muscle. During revision surgery, a 4 x 6.5-cm bone
      shell that consisted primarily of immature trabecular bone and lamellar bone in
      smaller proportions was removed. The case presented here is unique in the
      scientific literature. Although risk factors have been identified, the underlying
      pathomorphogenetic mechanism of such heterotopic bone formation remains unclear.
      Prophylactic administration of nonsteroidal anti-inflammatory drugs (NSAIDs) or
      radiation for arthroscopic or minimally invasive shoulder surgery is not
      justified, given the low incidence of heterotopic ossification and the known
      adverse effects. Apparently, information on basic science and on evidence-based
      therapy is lacking.

PMID- 18063186
TI  - Radial nerve palsy after arthroscopic anterior capsular release for degenerative
      elbow contracture.
AB  - Because the use of arthroscopy has increased recently for the treatment of elbow
      lesions, reports of complications have become more common. Nerve injury after
      arthroscopic anterior capsular release is an extremely rare complication, with 4
      reported cases worldwide. We usually use a sharp-tipped electrocautery device
      with a 0.5-mm diameter during arthroscopic capsular release. In this case,
      because the former was not prepared, we used a ball-tipped electrocautery device
      with a 3-mm diameter. Herein, we experienced a case of radial nerve palsy after
      arthroscopic anterior capsular release using a ball-tipped electrocautery device
      on a degenerative elbow contracture. We supposed that the electrocautery device
      caused transiently thermal injury of the radial nerve despite proper portal entry
      site, intra-articular distension, and gentle arthroscopic manipulation. Elbow
      arthroscopy remains a technically difficult procedure with the potential for
      neurologic complications. To perform surgery safely, knowledge of the regional
      neuroanatomy and a thorough understanding of proper instrument usage are
      required.

PMID- 18063187
TI  - Arthroscopic removal of an osteoid osteoma in the radial head: a case report.
AB  - We describe an unusual case of osteoid osteoma of the radial head that was
      treated by means of elbow arthroscopy. A 42-year-old man presented with a history
      of elbow pain lasting for 2 years that progressed after an unsuccessful previous
      operative procedure. Computed tomography and bone scan evaluation revealed the
      possibility of an osteoid osteoma of the radial head. Elbow arthroscopy under
      image intensifier guidance was completed to locate and remove the lesion. The
      shavings were collected, and a histologic analysis was performed, the findings of
      which were consistent with the preoperative diagnosis. An immediate decline in
      pain with an excellent and lasting increase in function was observed
      postoperatively. Radical open surgery is curative for osteoid osteoma and also
      allows for an excellent histologic confirmation of the diagnosis in the setting
      of a juxta-articular osteoid osteoma, but the residual morbidity does not justify
      it around accessible joint locations in this self-limited, albeit painful,
      disease. Thought should be given to the possibility of arthroscopic retrieval or
      excision with minimal operative damage before proceeding with open surgery. The
      use of a motorized instrument for excision does not preclude pathologic
      evaluation of the specimens.

PMID- 18063188
TI  - SLAP tear associated with a minimally displaced proximal humerus fracture.
AB  - Nondisplaced proximal humerus fracture may be associated with soft tissue injury.
      This case report examines 2 cases of superior labral anterior-posterior (SLAP)
      tears in association with nondisplaced fractures of the proximal humerus. In the
      first case, the patient fell from a jet ski, causing a traction injury to his
      arm. A greater tuberosity fracture was identified. Magnetic resonance imaging
      (MRI) did not reveal a definitive labral tear. After conservative management had
      failed, a type IV SLAP tear and a small rotator cuff tear were arthroscopically
      identified and repaired. In the second case, a power company lineman fell from a
      lift and attempted to hold on with his dominant arm. A nondisplaced greater
      tuberosity and a surgical neck fracture were discovered. MR arthrography revealed
      no evidence of SLAP tear. Four months after injury, a type II SLAP tear was
      arthroscopically identified and repaired. In these 2 cases, the presence of the
      fracture likely slowed operative intervention because pain was attributed to the
      fracture itself, and not to the SLAP tear. If patients do not follow the usual
      course of improvement after a proximal humerus fracture from a superior traction
      mechanism, consideration should be given to associated superior labral tears that
      may require surgical intervention.

PMID- 18063189
TI  - Accidental burn injury during knee arthroscopy.
AB  - A case is described in which hot irrigation fluid used during a routine knee
      arthroscopy caused severe morbidity. The patient sustained full-thickness skin
      burns requiring debridement, a muscle flap, and split-skin grafting. The extent
      of the joint damage required fusion. The underlying factors included equipment
      failure but also a delay in appreciating the severity of the soft-tissue damage.
      This case highlights the need for a robust protocol for the management of warming
      the irrigation fluid, as well as monitoring the actual fluid temperature.

PMID- 18063190
TI  - Proceedings of a Consensus Conference: pathogen inactivation-making decisions
      about new technologies.
AB  - Significant progress has been made in reducing the risk of pathogen transmission
      to transfusion recipients. Nonetheless, there remains a continuing risk of
      transmission of viruses, bacteria, protozoa, and prions to recipients. These
      include many of the viruses for which specific screening tests exist as well as
      pathogens for which testing is currently not being done, including various
      species of bacteria, babesiosis, variant Creutzfeld-Jacob disease, hepatitis A
      virus, human herpes virus 8, chikungunya virus, Chagas disease, and malaria.
      Pathogen inactivation (PI) technologies potentially provide an additional way to
      protect the blood supply from emerging agents and also provide additional
      protection against both known and as-yet-unidentified agents. However, the impact
      of PI on product quality and recipient safety remains to be determined. The
      purpose of this consensus conference was to bring together international experts
      in an effort to consider the following issues with respect to PI: implementation
      criteria; licensing requirements; blood service and clinical issues; risk
      management issues; cost-benefit impact; and research requirements. These
      proceedings are provided to make available to the transfusion medicine community
      the considerable amount of important information presented at this consensus
      conference.

PMID- 18063191
TI  - Men having sex with men donor deferral risk assessment: an analysis using risk
      management principles.
AB  - This article discusses issues associated with the lifetime deferral from donating
      blood of men having sex with men (MSM), in the context of well-established risk
      management principles, including ethical considerations associated with the risk
      based approach to social policy matters. Specifically, it deals with the
      questions about the rationale for the existing policy in Canada of lifetime
      deferral for MSM, a rationale applied in practice by blood collection agencies
      and supported by the regulatory authority of Health Canada. We identify several
      alternative time frames for MSM deferral: sexual abstinence over either a 10-, 5
      , or 1-year period or no deferral. Two options are selected for more complete
      discussion, namely, abstinence for a period of either 1 or 5 years before
      donation. The available evidence about estimated residual risk (RR)-that is, the
      risk remaining after various safeguards for blood are applied-strongly suggests
      that choosing a 1-year deferral period for MSM would almost certainly give rise
      to an incremental risk of transfusion-transmitted infection (TTI), over existing
      levels of risk, for blood recipients. The report argues that, under these
      circumstances, such a policy change would represent an unethical type of risk
      transfer, from one social group to another, and therefore would be unacceptable.
      The evidence is less clear when it comes to a change to either a 10- or 5-year
      deferral period. This is the case in part because the current level of RR is so
      low that there are, inevitably, substantial ranges of uncertainties associated
      with the risk estimation. There is no firm evidence that such a change in the
      deferral period for MSM would result in an incremental level of risk, although
      the possibility of a very small increase in risk cannot be entirely ruled out.
      Under these circumstances, other social policy issues, relevant to the idea of
      changing the deferral period for MSM, become worthy of additional consideration.

PMID- 18063192
TI  - Transfusion transmission of human prion diseases.
AB  - No transmission through transfusion has been reported for classic Creutzfeldt
      Jakob disease (CJD). Moreover, a series of epidemiological surveillance, case
      control, and look-back studies have provided no evidence of such transmission of
      CJD. Hence, the risk of such transfusion transmission of classic CJD remains
      theoretical. In contrast, based on data from the United Kingdom, the likelihood
      of transmission of the agent of the variant form of CJD (vCJD) through blood
      transfusion by donors who develop the disease within several years of donation is
      about 14% for recipients who survive longer than 5 years posttransfusion.
      Leukodepletion may reduce the likelihood of vCJD transmissions, although this
      procedure by itself removes less than half of the prion infectivity of blood. The
      potentially longer incubation periods of vCJD with infections in donors who are
      not methionine/methionine homozygous at codon 129 of the prion protein gene, the
      unknown number of such donors, and the unknown infectivity of their blood during
      the incubation period suggests caution in assuming that only known cases of vCJD
      represent a risk for the transfusion transmission of vCJD. Results from ongoing
      look-back investigations and other studies will enable continued monitoring and
      more precise estimations of the risks of the transfusion transmission of CJD and
      vCJD.

PMID- 18063193
TI  - Transfusion medicine during the summer of 2006: lessons learned in northern
      Israel.
AB  - In July 2006 a Hizballah attack erupted at the Lebanon-Israel border. Reported
      here is the experience of the Rambam Health Care Campus--a level I trauma center-
      during 33 days of warfare. Two hundred ninety-five soldiers and 209 civilians
      were admitted to the emergency department (ED). Forty-eight wounded soldiers
      (16%) and 12 civilians (6%) had transfusion. Twenty soldiers and 1 civilian had
      massive transfusions. The ratio between packed red blood cells and fresh frozen
      plasma (FFP) used for patients who had massive transfusion was 3:2. In these
      patients, the median prothrombin time international normalized ratio and partial
      thromboplastin time increased during the first 2 hours after admission from 1.29
      to 1.51 and from 33.6 to 39 seconds, respectively. Twenty patients who had
      massive transfusion survived. Patients with an injury severity score of at least
      16 had a higher need for blood products than others, with a lower severity score,
      with a mean packed red blood cells unit transfusion of 7 vs 4 (P = .03) and FFP
      transfusion of 13 vs 1.5 (P = .002), respectively. In conclusion, we observed
      that early transfusion of FFP to casualties with penetrating wounds requiring
      massive transfusion is needed to overcome the coagulopathy present. The presence
      of a transfusion service representative on-site in the ED is recommended to
      ensure proper identification and labeling of blood samples. Real-time
      consultations provided by a transfusion medicine physician in the operation
      theater was also found to be essential.

PMID- 18063194
TI  - Canadian surgeons and the introduction of blood transfusion in war surgery.
AB  - Canadian surgeons serving in the Canadian Army Medical Corps in the First World
      War were responsible for introducing transfusion in the management of war
      casualties to the British Army. They were uniquely placed to do so by a
      coincidence of circumstances. They were aware of developments occurring in the
      field of blood transfusion in the United States, which was at the time leading
      the research and development of transfusion as a therapeutic measure. The ties
      between Britain and Canada in 1914 were such that Canada entered the war
      immediately, and Canadians served closely with the British, volunteering promptly
      and in large numbers. Britain, by contrast with the United States, had little
      interest in or expertise with blood transfusion. Thus, Canadian surgeons went to
      war aware of the value of blood transfusion and with some who had actually
      learned how to use transfusion. They arrived to find no interest or expertise on
      the part of their British colleagues and had to work hard to convince them of the
      merits of blood transfusion in the management of hemorrhage. Their efforts were
      reinforced by the arrival in 1917 of American surgeons bringing their experience
      with transfusion. By war's end, blood transfusion was generally accepted as the
      treatment of choice for severe blood loss.

PMID- 18063195
TI  - Erlotinib administration for advanced non-small cell lung cancer during the first
      2 months of unrecognized pregnancy.
AB  - Although several antineoplastic agents have been proven to be safe for the fetus
      after the organogenesis period, there is limited information on their use during
      the first trimester of pregnancy. Herein we report the first case of a patient
      with metastatic lung cancer treated with erlotinib during the first 2 months of
      an unrecognized pregnancy. A 30-year-old woman was diagnosed with stage IV non
      small cell lung cancer with bone and lung metastasis. The patient received 4
      months of palliative cisplatin/gemcitabine chemotherapy and biphosphonates. After
      12 months the disease progressed and the patient received erlotinib 100 mg/day.
      During this period the patient became pregnant. Since she recalled the date of
      her last menstrual period at about 15 days prior to the start of the therapy, we
      did consider the possibility of conception at the time of the first day of
      erlotinib administration. Informed about the risk for the fetus due to erlotinib,
      the patient stopped anticancer treatment. After 42 weeks of regular gestation,
      cesarean section was performed, delivering a 3490 g female new-born with no
      evidence of congenital malformations. The disease evaluation performed with
      thoracic CT scan, after 1 month from the childbirth, showed a progressive lung
      metastasis and erlotinib treatment was resumed at the dose of 150 mg/day.

PMID- 18063196
TI  - Janus face of Nrf2-HO-1 axis in cancer--friend in chemoprevention, foe in
      anticancer therapy.

PMID- 18063197
TI  - Undergraduate nursing students' knowledge and perception of infection prevention
      and control.

PMID- 18063198
TI  - Evaluation of risk factors for the acquisition of bloodstream infections with
      extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella
      species in the intensive care unit; antibiotic management and clinical outcome.
AB  - Controlled studies that address risk factors for, and clinical outcomes after,
      infection with extended-spectrum beta-lactamase (ESBL)-producing organisms are
      scant, particularly in the intensive care unit (ICU). Our objectives were to
      elucidate risk factors for the acquisition of ESBL-producing organisms in ICU;
      and to compare mortality in patients with ESBL- and non-ESBL bloodstream
      infections (BSIs) after controlling for disease severity and timeliness of
      appropriate antibiotic therapy. A retrospective cohort study was undertaken in
      the ICU from March 2004 to May 2006. Cases included all adult ICU patients with a
      BSI due to an ESBL-producing E. coli or Klebsiella spp. (N=16); controls (N=39)
      comprised ICU patients with a BSI caused by a non-ESBL-producing E. coli or
      Klebsiella spp. Disease severity was measured using APACHE (Acute Physiological
      Assessment and Chronic Health Evaluation) and SOFA (Sequential Organ Failure
      Assessment) scores. Outcomes were recorded as discharge or death due to all
      causes. Although no statistically significant associations were demonstrated
      between individual risk factors and the acquisition of an ESBL-producing
      organism, appropriate therapy was delayed in cases (OR: 9.17; 95% CI: 2.00-42.20;
      P=0.0005) and survival estimates demonstrated a significantly increased early
      (<25 days after infection) mortality (OR for death 3.93; 95% CI: 1.05-14.63;
      P=0.03). Mortality in ICU, when adjusted for disease severity and appropriate
      antimicrobial therapy, though significant needs to be treated with caution due to
      the small number of cases (N=16 in 2 years). We believe that a high index of
      suspicion, early appropriate therapy and strict adherence to infection control
      are indicated in all patients at risk in ICU.

PMID- 18063199
TI  - An outbreak caused by multidrug-resistant OXA-58-positive Acinetobacter baumannii
      in an intensive care unit in Italy.

PMID- 18063200
TI  - C-type natriuretic peptide and its relation to non-invasive indices of left
      ventricular function in patients with chronic heart failure.
AB  - C-type natriuretic peptide (CNP) significantly increases in chronic heart failure
      (CHF) patients as a function of clinical severity. Aim of this study was to
      evaluate in CHF patients the relationship between circulating CNP concentrations
      and echo-Doppler conventional indices of left ventricular (LV) function as well
      as less load independent parameters as dP/dt. LV ejection fraction (EF), left
      ventricular end-diastolic dimension (LVEDD) and LV dP/dt were evaluated together
      with plasma CNP levels in 38 patients with CHF and in 63 controls. CNP levels
      resulted significantly higher in CHF patients than in controls (7.19+/-0.59 pg/ml
      vs. 2.52+/-0.12 pg/ml, p<0.0001). A significant correlation between dP/dt and CNP
      levels (r=-0.61, p<0.0001) was observed. A good correlation with EF (r=-0.55,
      p<0.001) and a less significant relation with LVEDD (r=0.316, p<0.05) were also
      reported. When patients were divided according to dP/dt values a very significant
      difference in CNP levels was observed: Group I (<600, n=25) vs. Group II (>600,
      n=13): 8.46+/-0.69 and 4.75+/-0.75 pg/ml, respectively, p<0.001. This is the
      first study that reports a correlation between CNP and dP/dt in CHF patients,
      thus suggesting a possible role on cardiac contractility.

PMID- 18063201
TI  - A training model for central venous cannulation for everyman?

PMID- 18063202
TI  - Inexpensive homemade models for ultrasound-guided vein cannulation training.
AB  - STUDY OBJECTIVE: To test the hypothesis that low-cost homemade models may be used
      to acquire the basic skills for ultrasound-guided central vein puncture. DESIGN:
      Training study. SETTING: University transplantation department. MEASUREMENTS:
      Training was performed using three different homemade models (A, B, and C).
      Segments of a common rubber tourniquet (V1) and Silastic tube (V2) were used to
      simulate vessels within agar-based models. Overall cost for each model was less
      than 5 euro (US$7). For each test (test I, A-V1; II, A-V2; III, B-V1; IV, C-V2),
      the number of punctures and attempts needed to locate the needle inside the lumen
      were recorded. Each test was considered completed when participants punctured the
      vessels at the first attempt for three consecutive times. MAIN RESULTS: In test
      I, the mean number of punctures and attempts were 3.85 +/- 1.26 and 4.95 +/-
      3.05; in test II, 4.60 +/- 1.14 and 6.30 +/- 2.51; in test III, 4.80 +/- 1.06 and
      4.65 +/- 2.21; and in test IV, 4.45 +/- 1.23 and 6.05 +/- 2.92, respectively. For
      each test, no statistical difference was found by comparison of number of
      punctures and attempts for anesthesiologists versus nonanesthesiologists, men
      versus women, or previous experience versus no experience with central vein
      cannulation (CVC). Video game users obtained better results than did nonusers in
      test I (punctures, P = 0.033; attempts, P = 0.038), test II (punctures, P =
      0.052; attempts, P = 0.011), and test IV (punctures, P = 0.001; attempts, P =
      0.003). A posttraining questionnaire showed favorable opinions about the clarity
      of the instructions, aptness of the models, and adequacy of the training. In our
      operative unit, the use of ultrasound guidance for CVC increased from 2% to 23%
      in the first month after training. CONCLUSION: Low-cost homemade models are
      useful in acquiring basic coordination skills for ultrasound-guided CVC.

PMID- 18063203
TI  - Time course of systolic and diastolic blood pressure decreases during the
      preintubation period of anesthesia induction: modeling with a logistic function.
AB  - STUDY OBJECTIVE: To investigate whether systolic (SBP) and diastolic blood
      pressure (DBP) decreases during the preintubation period could be expressed as 4
      parameter logistic and cubic functions giving S-shaped curves. DESIGN:
      Prospective, clinical study. SETTING: Operating room of a metropolitan general
      hospital. PATIENTS: Seven ASA physical status I and II patients scheduled for
      elective spinal surgery during general anesthesia. INTERVENTIONS: Anesthesia was
      induced with fentanyl, propofol, and vecuronium injection followed by inhalation
      of sevoflurane. MEASUREMENTS: The SBP and DBP data were recorded at all beats
      from fentanyl injection to direct laryngoscopy. The respective changes were
      analyzed using a logistic function: P(t) = p(L) + (q(L) - p(L))/(1 + exp{[4
      m(L)/(q(L) - p(L))][k(L) - t]}) and a cubic function: P(t) = at(3) + bt(2) + ct +
      d, where parameter p(L) is the upper asymptote, q(L) is the lower asymptote, m(L)
      is the slope at the inflection point, and k(L) is the time to the inflection
      point and where a, b, and c are coefficients, and d are constants. Goodness of
      fit of the two functions was compared using a correlation coefficient and
      residual mean squares. Each parameter was compared with the corresponding
      observed data. MAIN RESULTS: Logistic correlation coefficient values for SBP and
      DBP decreases were larger than the cubic correlation coefficient values (0.990 [Z
      transformation: 2.64 +/- 0.32] vs 0.981 [Z: 2.32 +/- 0.37] and 0.977 [Z: 2.22 +/-
      0.33] vs 0.967 [Z: 2.05 +/- 0.34], respectively; P < 0.05). Logistic residual
      mean squares values for SBP and DBP decreases were smaller than cubic residual
      mean squares values (20.6 vs 41.0 and 9.2 vs 13.7 mmHg(2), respectively; P <
      0.05). There were significant correlations between p(L) and SBP or DBP after
      anesthesia induction, between q(L) and SBP or DBP before endotracheal intubation,
      and between k(L) and time to maximal rate of the SBP or DBP decrease
      (dP/dt(min)), but no significant correlation between m(L) and dP/dt(min) for SBP
      or DBP. CONCLUSIONS: Time courses of SBP and DBP decreases during the
      preintubation period of anesthesia induction are modeled effectively by a
      logistic function.

PMID- 18063204
TI  - Interpleural versus epidural analgesia with ropivacaine for postthoracotomy pain
      and respiratory function.
AB  - STUDY OBJECTIVE: To evaluate the impact of interpleural analgesia (IP) on
      postthoracotomy pain and respiratory function as an alternative to thoracic
      epidural analgesia (TEA). DESIGN: Prospective, randomized study. SETTING:
      Tertiary-care military hospital. PATIENTS: Sixty young patients scheduled for
      elective thoracic surgery (correction of aorta coarctation and patent ductus
      arteriosus). INTERVENTIONS: Patients were randomized into two groups to receive
      either IP or TEA for postthoracotomy pain management. MEASUREMENTS: Patients in
      the IP group (n = 30) had a catheter inserted between the parietal and visceral
      pleura by a surgeon, and 0.2% ropivacaine was given through this catheter. In the
      TEA group, ropivacaine was administered through a thoracic epidural catheter. The
      impact of both methods on pain control, respiratory function, and pulmonary
      complications was analyzed and compared. MAIN RESULTS: The frequency of
      atelectasis and pleural effusion was also significantly high in the IP group (P <
      0.01). Respiratory function and postoperative pain scores were better in the TEA
      group (P < 0.01). Arterial blood gas analysis on the fifth postoperative day was
      significantly better in the TEA group. CONCLUSION: Thoracic epidural analgesia
      has more beneficial effects on respiratory function and postoperative pain after
      thoracotomy than does IP.

PMID- 18063205
TI  - Preemptive antiemesis in patients undergoing modified radical mastectomy: oral
      granisetron versus oral ondansetron in a double-blind, randomized, controlled
      study.
AB  - STUDY OBJECTIVE: To assess the efficacy of oral granisetron versus oral
      ondansetron for preemptive antiemesis in women undergoing modified radical
      mastectomy. DESIGN: Randomized, double-blind, controlled study. SETTING:
      Metropolitan hospital. PATIENTS: Ninety ASA physical status I and II hospitalized
      female patients, aged 18 to 65 y, scheduled for modified radical mastectomies.
      INTERVENTIONS: Patients were assigned to receive orally placebo, granisetron 2
      mg, or ondansetron 4 mg (n = 30 in each group) 1 h before induction of
      anesthesia. A standard general anesthetic technique and postoperative analgesia
      were used. MEASUREMENTS: Postoperative nausea and vomiting and safety assessments
      were performed continuously 0 to 2, 2 to 6, 6 to 12, and 12 to 24 h after
      anesthesia. MAIN RESULTS: A complete response during 0 to 2 h after anesthesia
      was found in 43%, 63%, and 90% of patients who had received placebo, granisetron,
      or ondansetron, respectively; corresponding percentages of patients requiring
      rescue antiemetics were 40%, 17%, and 7%. Frequency of nausea and vomiting was
      low (less than 23%) after 2 h in the three groups. Observations of postoperative
      nausea and vomiting score and need for antiemetics at other time intervals (2 to
      6, 6 to 12, and 12 to 24 h) were not significantly different among the three
      groups. CONCLUSION: Oral ondansetron 4 mg provided better preemptive antiemesis
      than oral granisetron 2 mg in the 2 h after modified radical mastectomy during
      general anesthesia.

PMID- 18063206
TI  - Self-reported changes in attitude and behavior after attending a simulation-aided
      airway management course.
AB  - STUDY OBJECTIVE: To evaluate the influence of a simulator-aided course for airway
      management on participants' daily clinical airway management practice. DESIGN:
      Survey instrument. SETTING: University hospital. PARTICIPANTS: 88 participants
      who attended a simulator-aided course for airway management. INTERVENTION: Six mo
      after 4 consecutive courses with identical structure and content, participants
      were mailed a standardized questionnaire to answer. MEASUREMENTS AND MAIN
      RESULTS: Of 88 participants queried, 48 completed the questionnaire. Ninety-two
      percent had experienced a difficult airway situation in the 6 mo after the
      course. Fourteen (29%) evaluated predictors for a difficult airway more
      carefully. Fourteen (29%) established structural changes within their
      departments. Ten (21%) participants acquired new technical airway devices. The
      mean estimated impact on the participants' rating for lectures, skill stations,
      and scenarios on a scale from 1 (very helpful) to 6 (not at all helpful) was 2.8
      for lectures, 1.6 for skill stations, and 1.4 for scenarios. CONCLUSIONS:
      Attendance at a simulator-aided airway management course has a significant impact
      on self-reported accuracy and confidence in evaluation of airways, use of
      alternative airway devices, and changes in the practitioner's clinical practice
      toward difficult airway situations.

PMID- 18063207
TI  - The effect of landiolol on hemodynamics and left ventricular function in patients
      with coronary artery disease.
AB  - STUDY OBJECTIVE: To examine the effect of landiolol (normal dose) on hemodynamics
      and left ventricular (LV) function. DESIGN: Prospective, observational, repeated
      measures study. SETTING: University hospital. PATIENTS: 56 adult patients who
      were diagnosed with angina pectoris and who underwent elective off-pump coronary
      artery bypass surgery. INTERVENTIONS: Patients were divided into two groups based
      on a preoperative LV ejection fraction (EF) 50% or higher (normal EF group, n =
      28) and lower than 50% (low EF group, n = 28). Hemodynamics and LV function were
      recorded using a pulmonary artery catheter and transesophageal echocardiography
      at three time points (before administration of landiolol, immediately before
      completion of administration, and 15 minutes after completion of administration).
      MEASUREMENTS: Individual hemodynamic data were obtained using a pulmonary artery
      catheter, and individual parameters were determined from LV short-axis views in
      transesophageal echocardiography. MAIN RESULTS: Mean preoperative EFs were 57% +/
      5% and 47% +/- 3% in the normal and low EF groups, respectively. In both groups,
      landiolol produced a significant decrease in heart rate (HR), which then returned
      to baseline 15 minutes after completion of administration. A significant decrease
      in mean arterial pressure occurred in the low EF group, but the decrease was
      within 30% of baseline. In the normal EF group, there was no decrease in cardiac
      index, but a significant increase in stroke index, in addition to an increase in
      stroke volume. In the low EF group, cardiac index significantly decreased along
      with the decrease in HR, but there was no increase in end-diastolic volume or
      stroke volume. CONCLUSIONS: Administration of landiolol using the presently
      recommended dosage and administration route causes a decrease in HR without
      aggravation of hemodynamics in patients with normal cardiac function, but in
      patients with preoperative EF lower than 50%, it may lead to further
      deterioration of cardiac function due to a decrease in HR.

PMID- 18063208
TI  - Metoclopramide does not influence the frequency of propofol-induced spontaneous
      movements.
AB  - STUDY OBJECTIVE: To evaluate the effects of metoclopramide on the frequency and
      severity of propofol-induced movements. DESIGN: Randomized, double blind, placebo
      controlled trial. SETTING: Veterans Administration Medical Center. PATIENTS: One
      hundred thirty-seven consenting adults scheduled to receive general anesthesia
      with propofol induction. INTERVENTIONS: Patients were randomized to receive
      either metoclopramide 10 mg intravenously (IV) or placebo (saline) 3 min before
      induction of general anesthesia. All patients received midazolam 1 to 2 mg IV,
      fentanyl 50 to 150 microg IV, and lidocaine 50 to 80 mg IV before induction of
      anesthesia. MEASUREMENTS: Occurrence of spontaneous movements and severity during
      the observation period were recorded after propofol induction by observing
      movement in the hands/arms and feet/legs, as well as presence of a hiccup. The
      dosage of anesthetic medications administered was also recorded for each patient.
      MAIN RESULTS: No differences were noted in the frequency and severity of
      spontaneous movement in the patients who had received metoclopramide and placebo.
      However, compared with the patients who did not move, patients who experienced
      movements received a significantly higher dose of propofol (P = 0.025) and a
      lower dose of fentanyl (P = 0.049). CONCLUSIONS: Metoclopramide does not affect
      the frequency of propofol-induced movements, but propofol and fentanyl doses
      influence the frequency of movements during propofol induction.

PMID- 18063209
TI  - Comparison of analgesia induced by continuous epidural infusion of plain 1%
      lidocaine and 1% lidocaine prepared by dilution of 2% lidocaine with the same
      volume of saline.
AB  - STUDY OBJECTIVE: To compare the extent of sensory block induced by continuous
      epidural infusion of plain 1% lidocaine and 2% lidocaine diluted with saline to
      1% lidocaine. DESIGN: Prospective, randomized, blinded study. SETTING: University
      hospital. PATIENTS: 40 ASA physical status I inpatients scheduled for lower
      extremity orthopedic surgery. INTERVENTIONS: After surgery with lumbar epidural
      anesthesia with 0.75% ropivacaine, patients were randomized to two postoperative
      epidural infusion groups to receive plain 1% lidocaine (plain group) or 2%
      lidocaine diluted with the same volume of normal saline (dilution group).
      Continuous epidural infusion was started at a rate of 6 mL/h. MEASUREMENTS AND
      MAIN RESULTS: Regression of sensory block was significantly prolonged in the
      plain group, resulting in a significant difference in the spread of sensory block
      between the two agents from 4 to 6 h postoperatively. There also was a
      significant difference from the two groups in the level of motor block (modified
      Bromage scale) between 3 and 5 h postoperatively. CONCLUSIONS: Two percent
      lidocaine diluted with the same volume of saline is a less potent than the plain
      1% lidocaine. The effect of saline as a diluent on epidurally administrated local
      anesthetics may be of clinical importance.

PMID- 18063210
TI  - Postlaryngectomy hypertensive crisis: a manifestation of perioperative acute
      baroreflex failure?
AB  - Hemodynamic instability as a result of altered baroreflex mechanism is common in
      surgeries involving manipulation around the carotid sheath. We report a case in
      which hypertensive crisis was associated with laryngectomy during general
      anesthesia. Perioperative use of vasoactive agents such as alpha(2) agonists may
      help in maintaining hemodynamic stability in such procedures.

PMID- 18063211
TI  - Exacerbation of myasthenia gravis after tourniquet release.
AB  - By avoiding use of neuromuscular blocking agents, regional anesthesia techniques
      may allow safer care of patients with myasthenia gravis. We describe a patient
      who had myasthenic crisis after foot surgery during spinal anesthesia. Lactate
      released on deflation of bilateral tourniquets constituted the most likely cause
      of the exacerbation.

PMID- 18063212
TI  - Tension pneumothorax and cardiac arrest from an improvised oxygen delivery
      system.
AB  - An improvised mechanism for delivering supplemental oxygen to a spontaneously
      breathing, tracheally intubated patient set the stage for a case of barotrauma,
      bilateral tension pneumothorax, and cardiovascular collapse. Diagnosis and
      treatment was delayed by failed needle decompression of the pneumothoraces.
      Recommendations are made regarding the prevention and treatment of this
      complication to improve patient safety.

PMID- 18063213
TI  - Postpartum seizures after epidural analgesia: a patient with a mutation of the
      factor V Leiden and prothrombin gene.
AB  - We report the case of a 27-year-old parturient who developed a headache within 12
      hours of delivery and who subsequently seized. Further examination, including
      magnetic resonance imaging and computed tomographic scan, showed a partial
      thrombosis of a transversal venous sinus, the underlying cause being an activated
      protein C resistance caused by a heterozygote factor V Leiden mutation and
      heterozygote prothrombin-gene mutation G20210A. Seven months after delivery, the
      patient is in good health, showing no neurocognitive disability.

PMID- 18063214
TI  - Tracheal anomalies complicating ventilation of an infant with Apert syndrome.
AB  - Apert syndrome is a rare autosomal dominant disorder characterized by severe
      syndactyly of the feet and hands, craniofacial abnormalities, and
      craniosynostosis. A 7-month-old male infant with Apert syndrome who underwent
      direct bronchoscopy and tracheotomy during general anesthesia is presented. Early
      rigid bronchoscopy is important in these patients when there are problems with
      the airway, as they have a relatively high incidence of airway anomalies.

PMID- 18063215
TI  - Anaphylaxis to vecuronium: the use of basophil CD63 expression as a possible
      screening tool to identify a safe alternative.
AB  - A 29-year-old woman with a history of anaphylaxis during anesthesia required
      diagnostic laparoscopic surgery for investigation of infertility. Previous
      laboratory investigations suggested that she had reacted to vecuronium, but she
      also had a specific IgE antibody to succinylcholine. The use of the basophil
      activation marker CD63 as a screening tool in selecting a safe muscle relaxant is
      presented.

PMID- 18063216
TI  - My brother's keeper: must a physician disclose another's medical error and
      potential negligence?

PMID- 18063217
TI  - Nasotracheal intubation with the aid of the Airway Scope.

PMID- 18063218
TI  - Malfunctioning dual valve antireflux Y-connector set.

PMID- 18063219
TI  - A difficult airway case with GlideScope-assisted fiberoptic intubation.

PMID- 18063220
TI  - Impacted gum-elastic bougie in an endotracheal tube after successful intubation
      of a difficult airway.

PMID- 18063221
TI  - A detachable, reinforced laryngeal mask airway for transnasal application in oral
      surgery.

PMID- 18063222
TI  - SORL1 haplotypes modulate risk of Alzheimer's disease in Chinese.
AB  - Genetic variants of the neuronal sortilin-related receptor (SORL1) have been
      demonstrated to modulate the risk of Alzheimer's disease (AD) in different
      American and European populations [Rogaeva, E., Meng, Y., Lee, J.H., Gu, Y.,
      Kawarai, T., Zou, F., Katayama, T., Baldwin, C.T., Cheng, R., Hasegawa, H., Chen,
      F., Shibata, N., Lunetta, K.L., Pardossi-Piquard, R., Bohm, C., Wakutani, Y.,
      Cupples, L.A., Cuenco, K.T., Green, R.C., Pinessi, L., Rainero, I., Sorbi, S.,
      Bruni, A., Duara, R., Friedland, R.P., Inzelberg, R., Hampe, W., Bujo, H., Song,
      Y.Q., Andersen, O.M., Willnow, T.E., Graff-Radford, N., Petersen, R.C., Dickson,
      D., Der, S.D., Fraser, P.E., Schmitt-Ulms, G., Younkin, S., Mayeux, R., Farrer,
      L.A., St George-Hyslop, P., 2007. The neuronal sortilin-related receptor SORL1 is
      genetically associated with Alzheimer disease. Nat. Genet. 39 (2), 168-177]. We
      conducted haloptype analysis involving two genetic clusters of SORL1 in AD and
      controls among Han Chinese. rs3824968 (SNP 23) was associated with an increased
      risk of AD, and there was a trend towards association for rs1699102 (SNP 22) and
      rs2282649 (SNP 24). More robust associations were found for three-loci
      haplotypes. In particular, the GCA haplotype at SNPs 19-22-23 was associated with
      an increased risk (odds ratio 1.4), and CTC haplotype at SNPs 19-22-23 and TCT at
      SNPs 22-23-24 a decreased risk (odds ratio 0.67) of AD. The complete absence of
      some at-risk North European haplotypes in our Chinese study subjects was likely
      due to different ancestral origins, with allelic heterogeneity among races.
      However, our study suggests that certain SORL1 haplotypes at SNPs 19-24 modulated
      risk of AD in our Chinese population.

PMID- 18063223
TI  - Hypoxia increases Abeta generation by altering beta- and gamma-cleavage of APP.
AB  - Environmental factors are significant contributors for the development of
      Alzheimer's disease (AD). The greatly increased incidence of AD following stroke
      and cerebral ischemia suggests that hypoxia is a risk factor which may accelerate
      AD pathogenesis by altering amyloid precursor protein (APP) processing. However,
      the molecular mechanisms underlying the hypoxia mediated AD pathogenesis have not
      been fully elucidated. In the present study we demonstrated that repeated hypoxia
      increased beta-amyloid (Abeta) generation and neuritic plaques formation by
      elevating beta-cleavage of APP in APP(swe)+PS1(A246E) transgenic mice. We also
      found that hypoxia enhanced the expression of APH-1a, a component of gamma
      secretase complex, which in turn may lead to increase in gamma-cleavage activity.
      Furthermore, we demonstrated that repeated hypoxia treatment can activate
      macroautophagy, which may contribute to the increases in Abeta production since
      pretreatment with macroautophagy inhibitor 3-methyladenine significantly blocked
      chemical hypoxic condition-induced increase in Abeta production in SH-SY5Y cells.
      Taken together, our results suggest an important role of hypoxia in modulating
      the APP processing by facilitating both beta- and gamma-cleavage which may result
      in a significant increase of Abeta generation.

PMID- 18063224
TI  - Synthesis of new substituted azetidinoyl and thiazolidinoyl-1,3,4-thiadiazino
      (6,5-b) indoles as promising anti-inflammatory agents.
AB  - Various N-({5-[(arylmethylene)amino]-1,3,4-thiadiazol-2-yl}methyl) [1,3,4]
      thiadiazino[6,5-b]indol-3-amine (6a-6h), 2-aryl-3-{5-[([1,3,4] thiadiazino[6,5
      b]indol-3-ylamino)methyl]-1,3,4-thiadiazol-2-yl}-1,3-thiazolidin-4-one (7a-7h),
      and 3-chloro-4-aryl-1-{5-[{[1,3,4]thiadiazino[6,5-b]indol-3-ylamino]methyl]-1,3,4
      thiadiazol-2-yl}azetidin-2-one (8a-8h) have been synthesized in the present
      study. The structure of these newly synthesized compounds were confirmed by their
      analytical and spectral data. These compounds were also evaluated for their anti
      inflammatory, ulcerogenic and analgesic activities. Compound 8g has shown most
      active anti-inflammatory and analgesic activities with better ulcerogenic
      activity than phenylbutazone, while this compound was found to be associated with
      lesser degree of anti-inflammatory and analgesic activities as compared to
      indomethacin.

PMID- 18063225
TI  - Novel keto-enamine Schiffs bases from 7-hydroxy-4-methyl-2-oxo-2H-benzo[h]
      chromene-8,10-dicarbaldehyde as potential antidyslipidemic and antioxidant
      agents.
AB  - A series of Schiff bases have been synthesized from dicarbaldehyde of
      benzocoumarin, in which the reactions were regioselective and the products
      existed in the keto-enamine form, in which the aromaticity of the relevant ring
      was disrupted. The compounds were evaluated in vitro for their antioxidant and in
      vivo for their antidyslipidemic activity for the first time. Compounds 3 and 7
      possess significant lipid lowering and antioxidant activity.

PMID- 18063226
TI  - The antioxidant activity of 2-(4(or 2)-hydroxyl-5-chloride-1,3-benzene-di
      sulfanimide)-chitosan.
AB  - Chitosan (CS) with two different molecular weights was modified by reacting with
      4-hydroxyl-5-chloride-1,3-benzene-disulfo-chloride or 2-hydroxyl-5-chloride-1,3
      benzene-disulfo-chloride to give new 2-(4(or 2)-hydroxyl-5-chloride-1,3-benzene
      di-sulfanimide)-chitosan (2-HCBSAHCS, 2-HCBSALCS, 4-HCBSAHCS, 4-HCBSALCS). The
      structure of the derivatives was characterized by FT-IR and 13C NMR spectroscopy.
      The antioxidant activities of the derivatives were investigated employing various
      established systems, such as hydroxyl radical (.OH)/superoxide anion (O2.-)
      scavenging/reducing power and chelating activity. All the derivatives showed
      stronger scavenging activity on hydroxyl radical than chitosan and ascorbic acid
      (Vc), and IC50 of 4-HCBSAHCS, 4-HCBSALCS, 2-HCBSAHCS and 2-HCBSALCS was 0.334,
      0.302, 0.442, 0.346 mg/mL, respectively. The inhibitory activities of the
      derivatives toward superoxide radical by the PMS-NADH system were strong. The
      results showed that the superoxide radical scavenging effect of 2-(4(or 2)
      hydroxyl-5-chloride-1,3-benzene-di-sulfanimide)-chitosan was higher than
      chitosan. The derivatives had obviously reducing power and slight chelating
      activity. The data obtained in in vitro models clearly establish the antioxidant
      potency of 2-(4(or 2)-hydroxyl-5-chloride-1,3-benzene-disulfanimide)-chitosan.

PMID- 18063227
TI  - New 1-indanone thiosemicarbazone derivatives active against BVDV.
AB  - Identification of new therapeutic agents for the treatment of viral diseases
      represents an area of active investigation. In an effort to develop new antiviral
      compounds, a series of 1-indanone thiosemicarbazone derivatives were synthesized.
      These derivatives were structurally characterized using several spectroscopic
      techniques and evaluated against bovine viral diarrhoea virus as a surrogate
      model for hepatitis C virus. Thiosemicarbazone 2m showed potent anti-bovine viral
      diarrhoea virus activity with a higher selectivity index (SI=80.29) than that of
      ribavirin (SI=11.64). This result determines the potentiality of these
      thiosemicarbazones as antiviral agents for the treatment of infections caused by
      other highly related members of Flaviviridae family, as hepatitis C virus.

PMID- 18063228
TI  - [Encrusted cystitis due to Corynebacterium urealyticum].
AB  - We reported the case of a 61 year-old man who presented an encrusted cystitis by
      Corynebacterium urealyticum associated with bilateral hydronephrosis four months
      after adenomectomy complicated by vesicocutaneous fistula. Medical treatment by
      quinolones and oral acidification of the urine allowed regression of the
      encrusted calcifications and resolution of the hydronephrosis.

PMID- 18063229
TI  - [Linear streaks on the back during dermatomyositis].

PMID- 18063231
TI  - EEG in premature less than 30 weeks of gestational age.

PMID- 18063230
TI  - Soy isoflavone intake increases bone mineral density in the spine of menopausal
      women: meta-analysis of randomized controlled trials.
AB  - BACKGROUND & AIMS: The effects of isoflavones on bone loss appear inconsistent in
      randomized controlled trials. Therefore, we used a statistical method of
      combining these diverse data to clarify the effects of soy isoflavone intake on
      spine bone loss. METHODS: We identified randomized controlled trials related to
      the effects of soy isoflavone intake on spine bone mineral density or spine bone
      mineral content and performed meta-analysis with Review Manager 4.2 software.
      RESULTS: Ten studies with a total of 608 subjects were selected for meta
      analysis. The spine bone mineral density in subjects who consumed isoflavones
      increased significantly by 20.6 mg/cm(2) (95% confidence interval: 4.5-36.6
      mg/cm(2)) in comparison to that in subjects who did not consume isoflavones.
      Isoflavone intake vs placebo intake increased spine bone mineral content by 0.93
      g (95% confidence interval: -0.37 to 2.24 g) with borderline significance.
      Increases in the spine bone mineral density with isoflavone intake of more than
      90 mg/day and with treatment lasting 6 months were 28.5mg/cm(2) (95% confidence
      interval: 8.4-48.6 mg/cm(2)) and 27 mg/cm(2) (95% confidence interval: 8.3-45.8
      mg/cm(2)), respectively. CONCLUSIONS: Isoflavone intervention significantly
      attenuates bone loss of the spine in menopausal women. These favorable effects
      become more significant when more than 90 mg/day of isoflavones are consumed. And
      soy isoflavone consumption for 6 months can be enough to exert beneficial effects
      on bone in menopausal women.

PMID- 18063232
TI  - Electroencephalography (EEG) recording techniques and artefact detection in early
      premature babies.
AB  - Electroencephalography (EEG) recording techniques in early premature babies are
      not very different from those used for full-term neonates. Here, we emphasise the
      most important points: asepsis precautions, full knowledge of the clinical data
      and drug therapies, fundamental role of a well-trained technician in supervising
      the EEG recording and monitoring the baby. We discuss the best electrode
      positions, the most informative montages, and their standardisation between
      neurophysiological laboratories. Artefact detection constitutes an important
      aspect of EEG signal analysis in preterm babies of less than 30 weeks. It is
      obviously necessary to discriminate between meaningful information and artefacts.
      The complexity of the signal in neonates makes artefact detection difficult. We
      present some characteristic features and describe some methods for eliminating
      them. We underline the positive aspect of some artefacts and their clinical use.
      We emphasise the crucial role of the technicians.

PMID- 18063233
TI  - Normal EEG of premature infants born between 24 and 30 weeks gestational age:
      terminology, definitions and maturation aspects.
AB  - This article presents normal EEG characteristics and their maturational pattern
      in premature infants of 24-30 weeks gestational age. Although the very premature
      infants with a normal outcome are not that numerous, their normal EEG pattern
      should be known, as EEG constitutes a basis for neurological prognosis.
      Background activity is first discontinuous but the discontinuity gradually
      decreases and the activity is completely continuous at 30 weeks of age, during
      active sleep. At the same time, interburst intervals become shorter so that the
      proportion of time without EEG activity decreases. Based on EEG activity and eyes
      movements, a rough sleep state differentiation appears as early as 25 weeks of
      gestational age and is complete at 30 weeks. The main EEG figures are high
      voltage delta waves, whose frequency is slower and amplitude higher in younger
      infants. Temporal delta waves occur in sequences and are characteristic of the
      very premature infant; they progressively become smaller and less numerous and
      disappear around 27-28 weeks. In contrast, occipital delta waves remain numerous;
      they are of high voltage and usually bilaterally superimposed with fast rhythms.
      Both types of frontal delta waves that are seen in 24-27 weeks premature babies
      disappear with maturation. Bursts of synchronized delta waves, which are less
      numerous than localized delta waves, also disappear before 28 weeks of
      gestational age. Finally, diffuse theta bursts which are mainly recorded at 26-27
      weeks, progressively focus on temporal areas with maturation. At 30 weeks, they
      are observed on temporal areas, mainly during slow-wave sleep.

PMID- 18063234
TI  - Pathological features of neonatal EEG in preterm babies born before 30 weeks of
      gestationnal age.
AB  - Pathological features on very premature EEG concern background abnormalities and
      abnormal ictal and nonictal patterns. Positive rolandic sharp waves keep an
      important place regarding diagnosis and prognosis of white-matter lesions.
      Background abnormalities, that may be classified as acute-stage or chronic-stage
      abnormalities, give essential complementary information. These abnormal patterns
      remain precocious markers of cerebral lesions and are complementary to cerebral
      imaging. Analysis of these abnormalities has always to take into account
      medication received by the baby during the recording and that could modify the
      EEG.

PMID- 18063235
TI  - Potent immunogenicity and efficacy of a universal influenza vaccine candidate
      comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand
      flagellin.
AB  - The recognition of specific pathogen associated molecular patterns (PAMPs) by
      members of the Toll-like receptor (TLR) family is critical for the activation of
      the adaptive immune response. Thus, incorporation of PAMPs into vaccines should
      result in more potent, protective antigen-specific responses in the absence of
      adjuvants or complex formulations. Here we describe an influenza A vaccine that
      is refractory to the genetic instability of hemagglutinin and neuraminidase and
      includes a trigger of the innate immune response to enhance immunogenicity and
      efficacy. A recombinant protein comprising the TLR5 ligand flagellin fused to
      four tandem copies of the ectodomain of the conserved influenza matrix protein M2
      (M2e) was expressed in Escherichia coli and purified to homogeneity. This
      protein, STF2.4xM2e, retained TLR5 activity and displayed the protective epitope
      of M2e defined by a monoclonal antibody, 14C2. Mice immunized with STF2.4xM2e in
      aqueous buffer, without adjuvants or other formulation additives, developed
      potent M2e-specific antibody responses that were quantitatively and qualitatively
      superior to those observed with M2e peptide delivered in alum. The antibody
      response was dependent on the physical linkage of the antigen to flagellin and
      recognized the epitope defined by monoclonal antibody 14C2, which has been shown
      to protect mice from challenge with influenza A virus. Moreover, immunization
      with STF2.4xM2e at a dose of 0.3 microg per mouse protected mice from a lethal
      challenge with influenza A virus, and significantly reduced weight loss and
      clinical symptoms. These data demonstrate that the linkage of specific TLR ligand
      with influenza M2e yields a vaccine candidate that offers significant promise for
      widespread protection against multiple influenza A virus strains.

PMID- 18063236
TI  - Plaque reduction neutralization test for measles antibodies: Description of a
      standardised laboratory method for use in immunogenicity studies of aerosol
      vaccination.
AB  - BACKGROUND: Clinical trials of measles vaccination administered as aerosol are
      planned with the aim of obtaining licensure. Measles antibody levels will be
      measured using the plaque reduction neutralization test (PRNT) to assess antibody
      responses as a surrogate marker of efficacy. METHODS: A working group examined
      laboratory protocols for measles PRNT in use at three reference centres and
      agreed to a standardised procedure, which was subsequently validated. RESULTS:
      Assay validation showed quantitative results varied approximately threefold both
      within and between assays. The lower limit of detection was approximately
      20milliInternational Units/mL. CONCLUSIONS: A standardised laboratory protocol
      for measles PRNT was established and validated for use in clinical trials of
      aerosolized measles vaccines.

PMID- 18063237
TI  - Comparison of Pu and (137)Cs as tracers of soil and sediment transport in a
      terrestrial environment.
AB  - Following atmospheric nuclear weapons testing in the 1950s and 1960s significant
      quantities of (137)Cs and (239+240)Pu were deposited worldwide. In recent
      decades, (137)Cs has been commonly used as a tracer of soil erosion and
      sedimentation, particularly in the Northern Hemisphere where atomic deposition
      was three times as great as in the Southern Hemisphere. The relatively short 30
      year half-life of this isotope means that its sensitivity as a tracer is rapidly
      decreasing. In contrast, with half-lives of 24,110 and 6561 years, the
      sensitivity of the two plutonium isotopes remains essentially the same as when it
      was deposited. Here we use the technique of Accelerator Mass Spectrometry to
      demonstrate the potential of anthropogenic Pu as an alternative to (137)Cs as a
      tracer of soil transport in Australia. We measure an average (137)Cs/(239+240)Pu
      activity ratio of 27.3+/-1.5 and an average (240)Pu/(239)Pu atom ratio of 0.149+/
      0.003, both slightly lower than the global average.

PMID- 18063238
TI  - Estimating the occupational morbidity for migrant and seasonal farmworkers in New
      York state: a comparison of two methods.
AB  - PURPOSE: Compare occupational morbidity estimates for migrant and seasonal
      farmworkers obtained from survey methods versus chart review methods and estimate
      the proportion of morbidity treated at federally recognized migrant health
      centers (MHCs) in a highly agricultural region of New York. METHODS: We
      simultaneously conducted 1) an occupational injury and illness survey among
      agricultural workers, 2) MHC chart reviews, and 3) hospital emergency room (ER)
      chart reviews. RESULTS: Of the 24 injuries reported by 550 survey subjects, 54.2%
      received treatment at MHCs, 16.7% at ERs, 16.7% at some other facility, and 12.5%
      were untreated. For injuries treated at MHCs or ERs, the incidence density based
      on survey methods was 29.3 injuries per 10,000 worker-weeks versus 27.4 by chart
      review. The standardized morbidity ratio for this comparison was 1.07 (95%
      confidence intervals = 0.65-1.77). CONCLUSIONS: Survey data indicated that 71% of
      agricultural injury and illness can be captured with MHC and ER chart review. MHC
      and ER incidence density estimates show strong correspondence between the two
      methods. A chart review-based surveillance system, in conjunction with a
      correction factor based on periodic worker surveys, would provide a cost
      effective estimate of the occupational illness and injury rate in this
      population.

PMID- 18063240
TI  - Why do women douche? A longitudinal study with two analytic approaches.
AB  - PURPOSE: Although vaginal douching is associated with several adverse outcomes,
      the reasons why women douche have not been studied prospectively. METHODS: Non
      pregnant (N = 3620) women aged 15 to 44 years presenting for routine care at 12
      clinics in Birmingham, Alabama, participated in a longitudinal study of vaginal
      flora (1999-2003). Participants were assessed quarterly for 1 year. The authors
      applied conditional logistic regression in a case-crossover analysis to determine
      the individual-level factors that vary between a woman's douching and non
      douching intervals. Findings were compared to a population-level analysis
      utilizing generalized estimating equations. RESULTS: Thirty percent of
      participants douched in every interval; 28% douched in some but not all
      intervals. The case-crossover analysis indicated a woman was more likely to
      douche when reporting "fishy" vaginal odor (odds ratio [OR]:2.74; 95% confidence
      interval [CI]: 1.55, 1.84), vaginal irritation (OR: 1.52; 95% CI: 1.10, 2.11),
      summer month (OR: 1.37, 95% CI: 1.13, 1.67), or increase in number of sex
      partners (> or = 3, OR: 2.42, 95% CI: 1.11, 5.26). Bacterial
      vaginosis/trichomoniasis treatment (OR: 0.72, 95% CL: 0.59, 0.89) and absent
      menses (OR: 0.37, 95% CI: 0.28, 0.50) were negatively associated with douching.
      These ORs were farther from the null than comparable population-level estimates.
      CONCLUSIONS: Programs targeting these predictors may decrease the untoward
      sequelae associated with douching. Furthermore, a case-crossover analysis applied
      to prospective studies can provide insights into time-varying factors.

PMID- 18063239
TI  - Newborn screening archives as a specimen source for epidemiologic studies:
      feasibility and potential for bias.
AB  - PURPOSE: To evaluate the feasibility of obtaining dried blood spots (DBS) from
      newborn screening archives for subjects in epidemiologic studies and using these
      specimens for genotyping, and to evaluate the potential for bias in their use.
      METHODS: We attempted to locate DBS at Washington State's archives for 230
      participants in a previous case-control study of childhood cancer, who were born
      1978-1990. We compared characteristics of children for whom we did and did not
      locate specimens and attempted genetic polymorphism analyses (11 polymorphisms,
      82-480 bp amplicons). RESULTS: We retrieved specimens for 203 (88%) children,
      including 199 (94%) born in months when a DBS catalog was available. Among the
      latter, the proportion with specimens located varied by birth place (e.g.,
      hospital, home), maternal education, and prenatal smoking, but did not vary
      significantly by race/ethnicity. All genotyping assays were completed for all
      specimens, and among controls genotype distributions were in Hardy-Weinberg
      equilibrium and similar to previous reports. CONCLUSIONS: Newborn screening
      archives have potential to provide specimens for epidemiologic studies conducting
      genotyping and perhaps other assays, but the possibility that reliance on these
      resources could bias risk estimates must be considered.

PMID- 18063241
TI  - Ambient formaldehyde levels and allergic disorders among Japanese pregnant women:
      baseline data from the Osaka maternal and child health study.
AB  - PURPOSE: The effects of formaldehyde (FA) exposure on allergic disorders are not
      clearly understood. This cross-sectional study examined the relationship between
      FA exposure and the prevalence of allergic disorders in Japan. METHODS: Subjects
      were 998 pregnant women. Participants were considered to have asthma, atopic
      eczema, or allergic rhinitis (including cedar pollinosis) if they had received
      any medical treatment for any of these allergic disorders during the previous 12
      months. Passive air sampling tubes were worn for 24 hours and analyzed for FA.
      RESULTS: When FA levels were categorized into four groups, there was a tendency
      for a positive exposure-response relationship between FA levels and the
      prevalence of atopic eczema, although the adjusted odds ratio for highest vs.
      lowest FA categories did not reach statistical significance. When FA levels were
      categorized into two groups to assess the effects of exposure to high levels of
      FA on allergic disorders, FA levels of 47 ppb or more were independently
      associated with an increased prevalence of atopic eczema (adjusted odds ratio =
      2.25; 95% confidence interval, 1.01-5.01). The positive association was more
      pronounced in women with a negative familial allergic history than in those with
      a positive familial allergic history. No clear association was found between FA
      levels and the prevalence of asthma or allergic rhinitis. CONCLUSIONS: FA
      exposure may be associated with an increased prevalence of atopic eczema in
      Japanese pregnant women.

PMID- 18063242
TI  - Emergency management of upper airway angio-oedema after routine dental extraction
      in a patient with C1 esterase deficiency.
AB  - Hereditary angio-oedema is rare and potentially life-threatening, being
      characterised by recurrent episodes of perioral or laryngeal oedema. We describe
      a 28-year-old woman who developed stridor, orofacial swelling, and drooling
      several hours after a routine dental extraction. This was initially diagnosed as
      a spreading dental infection. Only after early oral and maxillofacial review and
      taking a thorough family history was C1 esterase-inhibitor deficiency diagnosed.
      She was immediately given C1 esterase-inhibitor concentrate, made a complete
      recovery and was discharged next day.

PMID- 18063244
TI  - Synthetic facial implants.
AB  - This article presents a range of synthetic implant materials for use in facial
      plastic surgery. The authors discuss alternatives to autogenous tissue transfer
      in terms of biocompatibility, technique, complications, controversies, and
      cautions. The reader is presented information about a range of synthetic implant
      materials such as silicone, polyester fiber, polyamide mesh, metal, polyethylene,
      polyacrylamide gel, hydroxyapatite, polylactic acid, collagen, and others.

PMID- 18063245
TI  - Malar and submalar augmentation.
AB  - Over the past four decades, revolutionary improvements in the design and
      manufacture of facial implants have broadened the application of midface
      augmentation. The contemporary practice of facial rejuvenation reflects a 20-year
      culmination of rapid advances made in the understanding and treatment of midface
      aging. This article highlights the practice of malar and submalar augmentation:
      when and how it should be used.

PMID- 18063246
TI  - Alloplastic contouring for suborbital, maxillary, zygomatic deficiencies.
AB  - The authors have developed a new suborbital tear trough-malar extended implant
      that provides a comprehensive augmentation of the entire suborbital rim and malar
      region. The results have been excellent in all cases. There have been no
      postoperative symptoms relating to the infraorbital nerve. The major
      postoperative sequela is chemosis of a minor or significant degree in most
      patients. There have been four cases of a slightly retracted eyelid, which have
      resolved spontaneously in the course of 6 to 8 weeks. This technique does not
      require any removal of fat from the orbit nor does it require extensive
      dissection of fat. This operation successfully and satisfactorily creates an
      optimum blending of the lid-cheek junction.

PMID- 18063247
TI  - Chin augmentation.
AB  - This article reviews chin augmentation, describing patient evaluation and
      management, surgical technique, autogenous and alloplastic chin implants, their
      advantages and disadvantages, and potential complications.

PMID- 18063248
TI  - Custom-designed chin augmentation.
AB  - Although not devoid of complications, a properly performed chin implant surgery
      is a straightforward procedure that can correct a receding chin and enhance the
      results of other facial cosmetic procedures. In this article, the author reviews
      his technique over the last 18 years for augmentation mentoplasty using custom
      designed Mersilene mesh implants.

PMID- 18063249
TI  - The importance of the prejowl notch in face lifting: the prejowl implant.
AB  - This article reviews the anatomy of the lower face in light of approach and
      techniques for prejowl implant. Implant sizing, patient selection and analysis,
      technique, and complications are presented. The author cites the manner of aging
      in the lower face and discusses the concept of augmenting the mandible to re
      establish a youthful contour by correcting the prejowl sulcus and chin for
      rejuvenation. Because the prejowl sulcus and jowling camouflage the jawline,
      recontouring the mandible with implants restores the smooth jawline to provide
      optimal result by restoring the oval face shape.

PMID- 18063250
TI  - Customizing jawlines: the art of alloplastic premandible contouring.
AB  - Male patients are demanding alloplastic facial augmentation with a frequency that
      is increasing annually. Traditional methods of using small central chin implants
      and oval malar implants have proven inadequate. A new generation of malar shell
      and premandible implants has been designed; they produce dramatic and effective
      contour alterations in the midface and lower third chin-mandible facial aesthetic
      units. Principles of zonal anatomy and facial typing derived from facial
      architecture can facilitate great accuracy and precision of surgical execution.
      The special needs of the male patient must be addressed to create doctor and
      patient satisfaction.

PMID- 18063251
TI  - Nasal implants.
AB  - In this article, options for nasal implantation during rhinoplasty are discussed.
      The range of implant options currently available to the nasal surgeon is
      considered in detail. Various types of autografts, homografts, and alloplasts
      commonly used in the nose are introduced and described. Indications for each
      nasal implant type are considered, as are the advantages and limitations of each
      option.

PMID- 18063252
TI  - Custom-designed facial implants.
AB  - Accurate correction and restoration of facial contour defects have historically
      posed arduous challenges for reconstructive and aesthetic surgeons, but
      technological innovations in the design and manufacture of facial prostheses have
      significantly improved the precision, fit, and reliability of these restorative
      devices. This article discusses the experience with and benefits obtained by the
      use custom implants created using CT imaging and computer-aided design and
      manufacture.

PMID- 18063253
TI  - Factors related to exercise over the course of pregnancy including women's
      beliefs about the safety of exercise during pregnancy.
AB  - OBJECTIVE: to explore pregnant women's exercise patterns across pregnancy,
      reported reasons for exercising or not exercising, beliefs about the safety of
      exercise during pregnancy and the association of those beliefs with the amount
      and intensity of exercise that women participated in. DESIGN: a prospective
      questionnaire-based approach was implemented over three pregnancy time points 8
      weeks apart, with retrospective pre-pregnancy data obtained at the first time
      point. SETTING: participants were mailed questionnaires at 16-23-weeks pregnancy
      (T1), 24-31-weeks pregnancy (T2), and 32-38-weeks pregnancy (T3). PARTICIPANTS: a
      total of 158 pregnant women participated. MEASUREMENTS: at 16-23-weeks pregnancy
      women completed an Exercise Safety Beliefs Questionnaire in which they described
      their beliefs about the safety of low to medium exercise, high intensity
      exercise, gentle exercise, and weight bearing exercise. At T1, T2 and T3 reasons
      for exercising and not exercising were described, and participants maintained a 1
      week exercise diary in which they recorded amount and intensity of physical
      activity. Physical symptoms experienced over time were also reported. FINDINGS:
      the amount and intensity of exercise decreased over the course of pregnancy, with
      main reasons for not exercising including feeling tired or unwell, being too
      busy, and, particularly in late pregnancy, exercise being uncomfortable. Some
      women also reported safety concerns. Safety concerns predicted amount and/ or
      intensity of exercise. KEY CONCLUSIONS: overall, most women had clear beliefs
      about what forms of exercise were safe or not safe during pregnancy. Women who
      rated gentle and low to medium exercise as unsafe reported engaging in less
      intense and fewer minutes of exercise. IMPLICATIONS FOR PRACTICE: information and
      discussion about ways to exercise safely, enjoyably, and comfortably should be
      offered to pregnant women by health professionals in early pregnancy, when safety
      beliefs may impact on women's exercise patterns across pregnancy, and throughout
      pregnancy since the most appropriate forms of exercise may need to be modified
      over time.

PMID- 18063254
TI  - An alternative approach to reconstructing organic matter accumulation with
      contrasting watershed disturbance histories from lake sediments.
AB  - A number of proxies, including carbon to nitrogen ratio (C:N) and stable isotopes
      (delta(13)C and delta(15)N), have been used to reconstruct organic matter (OM)
      profiles from lake sediments and these proxies individually or in combination
      cannot clearly discriminate different sources. Here we present an alternative
      approach to elucidate this problem from lake sediments as a function of watershed
      scale land use changes. Stable isotope signatures of defined OM sources from the
      study watersheds, Shawnigan Lake (SHL) and Elk Lake (ELL), were compared with
      sedimentary proxy records. Results from this study reveal that terrestrial inputs
      and catchment soil coinciding with the watershed disturbances histories probably
      contributed in recent trophic enrichment in SHL. In contrast, cultural
      eutrophication in ELL was partially a result of input from catchment soil
      (agricultural activities) with significant input from lake primary production as
      well. Results were consistent in both IsoSource (IsoSource version 1.2 is a
      Visual Basic program used for source separation,
      (http://www.epa.gov/wed/pages/models/isosource/isosource.htm) and discriminant
      analysis (statistical classification technique).

PMID- 18063255
TI  - Analysis of micronucleated erythrocytes in heron nestlings from reference and
      impacted sites in the Ebro basin (N.E. Spain).
AB  - The frequency of micronuclei (MN) in peripheral erythrocytes was tested for 59
      heron nestlings (Ardea purpurea, Egretta garzetta and Bubulcus ibis) sampled at
      two areas (polluted and reference) on the River Ebro (NE Spain) and at its Delta
      during Spring 2006. Flow-cytometry analysis revealed higher (three- to six-fold)
      MN counts in samples from the most polluted site relative to samples from the
      reference area. Samples from the Delta showed intermediate values. Age,
      morphometric parameters (weight, tarsus size and bill-head length) and maturation
      status showed no significant differences among the different populations for each
      species; nor were they correlated with MN levels. The data suggest that elevated
      levels of MN in chicks in impacted areas reflected the chemical pollution of
      their nesting sites. The use of nestlings for this assay appears to be a
      convenient, non-destructive method to assess the impact of pollution in natural
      bird populations.

PMID- 18063256
TI  - Comparison of modelled and measured ozone concentrations and meteorology for a
      site in south-west Sweden: implications for ozone uptake calculations.
AB  - Measurements of ground-level ozone concentrations and meteorology (temperature,
      vapour pressure deficit (VPD), solar radiation) at the monitoring site Ostad
      (south-west Sweden) were compared to data from the corresponding grid in the EMEP
      photo-oxidant model for 1997, 1999 and 2000. The influence of synoptic weather on
      the agreement between model and measurements was studied. Implications of
      differences between modelled and observed inputs for ozone flux calculations for
      wheat and potato were investigated. The EMEP model output of ozone, temperature
      and VPD correlated well with measurements during daytime. Deviations were larger
      during the night, especially in calm conditions, attributed to local
      climatological conditions at the monitoring site deviating from average
      conditions of the grid. These differences did not lead to significant differences
      in calculated ozone uptake, which was reproduced remarkably well. The uptake
      calculations were sensitive to errors in the ozone and temperature input data,
      especially when including a flux threshold.

PMID- 18063257
TI  - Introduction. Necroinflammation and the course of chronic hepatitis.

PMID- 18063258
TI  - Therapy of chronic hepatitis B: focus on telbivudine.
AB  - Hepatitis B virus (HBV)viral load is closely related to necroinflammation and the
      outcome of chronic hepatitis B. The available treatment options to reduce viral
      load, and hence improve outcome, are either based on IFN or on
      nucleoside/nucleotide analogue antiviral agents, which inhibit HBVDNA
      replication. Use of IFN alfa or pegylated IFN alfa-2a for periods longer than 48
      weeks is limited by their side-effects. The antiviral agents have much more
      acceptable side-effect profiles, and lamivudine, the first antiviral to become
      available, was widely used until it became apparent that it carries a high
      potential for resistance to emerge, which rapidly negates its benefit. A new
      antiviral agent, telbivudine, has been approved in the USA and Europe and appears
      to be very rapid and potent against HBV, with an excellent safety profile.

PMID- 18063259
TI  - Cyclosporin in steroid-resistant autoimmune hepatitis and HCV-related liver
      diseases.
AB  - Cyclosporin has been used for many years in transplantation, and in this field
      its role is widely documented. However, other fields of application merit to be
      investigated, including the role of cyclosporin in treating autoimmune hepatitis
      and its possible role as an antiviral agent in hepatitis C virus (HCV) infections
      in both immunocompetent patients and in recipients of orthotopic liver
      transplants. Cyclosporin A has given promising results in small studies, and
      experience in transplantation and other immunological disorders indicates that
      its side-effects can be adequately managed. Cyclosporin certainly deserves
      further clinical investigation for first-line therapy in autoimmune hepatitis.
      Cyclosporin A suppresses the HCV genome dose-dependently in vitro at clinically
      relevant concentrations (150-250 ng/mL). The maximum effect is similar to that
      obtained with IFN alpha, and the effects of these two agents are certainly
      additive, and possibly synergistic. The inhibitory action of cyclosporin A
      appears to be independent upon its immunosuppressive action. Analysis of indirect
      endpoints in clinical trials on cyclosporin A for immunosuppression in transplant
      recipients indicates that cyclosporin A treatment can delay recurrence of HCV.
      Small, open label studies suggest that the observed anti-HCV activity of
      cyclosporin A can be translated into a real clinical benefit; nevertheless, these
      findings need to be confirmed in randomized, controlled clinical trials.

PMID- 18063260
TI  - Letter to the Editor.

PMID- 18063262
TI  - Presidential address: the neglected specialty.

PMID- 18063263
TI  - A colorectal curriculum for general surgery residents: are we ready for needs
      assessment?
AB  - OBJECTIVE: The traditional scope of general surgery (GS) has been broadly
      encompassing. Although it is generally accepted that we need a more defined
      curriculum for GS training, the criteria for limiting its scope remain
      controversial. One approach is to perform a needs assessment, defined based on an
      analysis of current GS practice. The purpose of this study was to use such a
      needs assessment to model a subset of the GS curriculum in colon and rectal
      surgery. DESIGN: The numbers of colon and anorectal procedures performed in the
      prior 24 months by 982 GS taking the 2004 ABS Recertification Examination in
      Surgery were examined to determine the mean number of procedures per surgeon
      along with the percentage of surgeons who had performed at least 1 of the
      identified procedures. The impact of using these numbers to define a general
      surgical curriculum was then examined. RESULTS: Procedures performed frequently
      and by >60% GS included appendectomies, colostomies, colectomies,
      hemorrhoidectomies, and anorectal abscess procedures. Procedures performed
      infrequently, yet performed by >30% of surgeons at least once, included subtotal
      colectomies, abdominoperineal resections, transanal excisions, sphincterotomies,
      and anorectal fistulotomies. The procedures performed rarely included ileoanal
      pouch anastomoses and procedures for incontinence and rectal prolapse.
      CONCLUSIONS: Based on this analysis, a colorectal surgical curriculum would
      include the treatment of diseases that led to commonly performed operations such
      as colon cancer, diverticular disease, lower gastrointestinal bleeding,
      mesenteric ischemia, inflammatory bowel disease (IBD), hemorrhoids, and anorectal
      diseases. The management of low rectal cancer, complex IBD, rectal prolapse, and
      fecal incontinence might not be essential content. A curriculum based on needs
      assessment would deemphasize or even eliminate some areas traditionally
      considered within the realm of GS. Although this might appropriately serve as a
      basis for defining the scope of GS, the indirect consequences will need to be
      defined.

PMID- 18063264
TI  - A multidisciplinary systems-based practice learning experience and its impact on
      surgical residency education.
AB  - OBJECTIVE: To design and implement a multidisciplinary systems-based practice
      learning experience that is focused on improving and standardizing the
      preoperative quality of care for general surgical patients. DESIGN: Four
      parameters of preoperative care were designated as quality assessment variables,
      including bowel preparation, perioperative beta-blockade, prophylactic antibiotic
      use, and deep venous thrombosis prevention. Four groups of general surgery
      residents (PGY I-V), each led by 1 chief resident, were assigned a quality
      parameter, performed an evidence-based current literature review, and formulated
      a standardized management approach based on the level of evidence and
      recommendations available. Because preoperative preparation includes anesthetic
      care and operating room preparation, we presented our findings at the Department
      of Surgery Grand Rounds in a multidisciplinary format that included presentations
      by each resident group, the Department of Anesthesia, the Department of Medicine,
      and the Department of Nursing. The aim of the multidisciplinary quality assurance
      conference was to present the evidence-based literature findings in order to
      determine how standardization of preoperative care would alter anesthetic and
      nursing care, and to obtain feedback about management protocols. To determine the
      educational impact of this model of integrated systems-based practice quality
      assessment on the teaching experience, residents were queried regarding the value
      of this educational venue and responses were rated on a Likert scale. RESULTS:
      Resident participation was excellent. The residents garnered valuable information
      by performing a literature review and evaluating the best preoperative
      preparation given each parameter. Furthermore, integration of their findings into
      systems-based practice including anesthesia and nursing care provided an
      appreciation of the complexities of care as well as the associated need for
      appropriate medical knowledge, communication, and professionalism. The derivation
      of treatment protocols included an opportunity to incorporate several
      competencies across multiple disciplines. The residents evaluated 5 questions and
      deemed the educational exercise an effective model to enrich surgical resident
      education while simultaneously improving patient care. The residents also
      strongly agreed that they would participate in similar projects in the future as
      well as recommend this educational exercise to other residents. A finalized
      preoperative order set was created and distributed to all residents for use in
      the preoperative care of general surgery patients. CONCLUSIONS: Our
      multidisciplinary systems-based practice learning experience focused on improving
      and standardizing the preoperative quality of care for patients, and general
      surgery residents were pivotal participants in that process. This exercise had a
      positive impact on our general surgery residency education program and proved to
      be a valuable model of systems-based practice competency.

PMID- 18063265
TI  - A new web-based operative skills assessment tool effectively tracks progression
      in surgical resident performance.
AB  - PURPOSE: The study aim was to demonstrate that a new database tool for assessment
      of surgical resident operative skills discerns predictable progression in those
      skills over successive residency years for specific index case types. METHODS: A
      Web-based interactive database (OpRate) was used to assess selected aspects of
      resident operative performance as determined by supervising attending surgeons in
      a medium-sized residency (5-6 residents per postgraduate year [PGY]). This
      assessment consisted of (1) 3 questions pertaining to patient information,
      technical, and disease-specific preparedness; (2) 4 laparoscopic technical skills
      questions pertaining to tissue handling, dexterity, planning, and ability to
      function independently; and (3) similar open technical skills questions, with the
      addition of 2 questions defining knot tying ability. Two years of assessment data
      were examined for cholecystectomy (CH), appendectomy (AP), colon resection (CR),
      ventral hernia repair (VH), and inguinal hernia repair (IH). Mean scores for
      total, technical, and preparedness responses, as well as each response area were
      compared for successive training years for each case type. Mean performance data
      between postgraduate years were compared by ANOVA, and interitem reliability was
      assessed by Cronbach's alpha determinations. RESULTS: OpRate data for 579 cases
      (142 CH, 67 AP, 73 CR, 202 IH, and 95 VH) were examined. Significant incremental
      increases in open and laparoscopic technical skills scores by training year were
      observed for all case types (ANOVA, p < 0.0001). Individual technical skills as
      well as technical and disease-specific preparedness response areas also
      demonstrated significant improvement by successive training year. Cronbach's
      alpha determinations were 0.80-0.94 for the preparedness test items and the
      skills performance scores for all assessed procedures. CONCLUSIONS: Our early
      results show that the OpRate assessment tool is effective in identifying expected
      changes in operative performance across successive training years, with a
      satisfactory level of internal consistency for the test items. As such, the use
      of this database tool may offer the opportunity to (1) define performance
      benchmarks for specific levels of training and (2) identify areas where focused
      training may be required for specific residents.

PMID- 18063266
TI  - A time-cost analysis of teaching a laparoscopic entero-enterostomy.
AB  - OBJECTIVE: Determining the success of technical skill training for surgery
      residents should include not only the efficacy of the training in terms of skills
      learned but also the cost of the facility where the training occurs and the cost
      of faculty participation. Traditional training occurs in the operating room, but
      the cost of faculty time and operating room time has not been well established.
      Assessing the cost of traditional training may allow us to put the cost of
      building and maintaining skills laboratories in perspective. To estimate the cost
      of traditional training we have recorded the time and interventions necessary for
      our senior residents to do a laparoscopic entero-enterostomy. METHODS: Each
      senior resident (PGY3-5) was asked to perform a laparoscopic entero-enterostomy
      in its entirety as part of a laparoscopic gastric bypass. After cannulation of
      the abdomen and division of any adhesions, we timed the residents for the
      performance of the following group of tasks: finding the ligament of Treitz,
      dividing the bowel 50-60 cm downstream, and creating a 2-layer anastomosis at 125
      or 200 cm distal to the ligament. We tracked total time and number of
      interventions, which are defined by the attending temporarily taking over the
      case. RESULTS: Twelve residents were tracked by this system. The average time to
      complete the task was 93.7 minutes (+/-11.9 SD). The average number of
      interventions per case was 1.5 (+/-1.1 SD). Nine residents completed more than 1
      procedure. Seven residents reduced their operative time on the second attempt.
      Operative times between the first and second procedure showed a reduction of 4.4
      minutes (+/-17.4 SD), although this was not statistically significant (p = 0.47).
      No adverse clinical sequelae developed in these small bowel anastomoses.
      Educational time was calculated by subtracting the resident time from the time it
      takes an attending or finishing laparoscopic fellow to complete this task (50
      minutes). The educational time for each anastomosis was 43.7 minutes. Using the
      AAMC average salary for an assistant professor of surgery of $180,000 year and
      assuming a 60-hour work week, this is $45.52 in faculty costs per anastomosis. If
      the cost of an operating room is $2000 per hour, the educational cost is $1457
      per anastomosis. In our program, providing our 15 senior residents an educational
      opportunity to perform 2 laparoscopic entero-enterostomies would cost $45,061 a
      year. CONCLUSION: Resident education is expensive. Knowledge of the cost of
      skills training in a traditional operative setting is necessary to put the costs
      associated with building and maintaining skills laboratories in perspective. Cost
      analyses and efficacy of teaching will allow us to rate the success of new
      educational techniques.

PMID- 18063267
TI  - An assessment of university versus independent general surgery program graduate
      performance on the American Board of Surgery examinations.

PMID- 18063268
TI  - Are the communication and professionalism competencies the new critical values in
      a resident's global evaluation process?
AB  - BACKGROUND: The ACGME requires the assessment of resident competency in 6
      domains. Global evaluations covering all 6 competencies are routinely used.
      Evaluators may be overly influenced by resident affability and availability,
      thereby resulting in a halo effect. We hypothesized that the Interpersonal Skills
      and Communications (ICS) and Professionalism (PR) competencies would unduly
      influence other competency scores. METHODS: General surgery resident evaluations
      are performed by staff and peers on a rotational basis using competency-based
      questions. Each question is scored using a 5-point Likert scale. Mean individual
      composite scores for each competency were calculated and then correlated with
      other mean composite competency scores. Data from patient evaluations were
      similarly analyzed. A final correlation of competency scores to ABSITE scores, as
      an objective, standardized measure of a specific competency, Medical knowledge
      (MK) was also performed. RESULTS: Results were available for 37 residents (PGY 1
      5). There was a significant association between ICS scores and higher scores in
      MK (r = 0.52, p = 0.004), PR (r = 0.826, p < 0.0001) and patient care (PC) (r =
      0.619, p < 0.0001). No correlation, however, was found between patient
      evaluations of residents and their faculty/peer-based ICS scores. We found no
      association between ICS scores and improved patient evaluations. Lastly, we found
      no association between ICS or MK scores and ABSITE scores. CONCLUSIONS: It was
      difficult to ascertain whether residents with better ICS scores had higher PR,
      PC, and MK scores because of the halo effect, improper completion of evaluations,
      or whether those residents were truly performing better clinically. External
      measures of resident performance did not correlate with faculty/peer evaluations
      of ICS and PR. Residency programs should consider adopting a more standardized
      way to objectively evaluate residents.

PMID- 18063269
TI  - Computerized rounding in a community hospital surgery residency program.
AB  - BACKGROUND: With the institution of the 80-hour work week, residency programs
      have worked to institute programs that decrease the time that residents spend in
      the hospital while maintaining patient safety. This study was intended to assess
      the amount of time saved using computerized patient information in the form of a
      personal data assistant (PDA). METHODS: A community hospital surgical residency
      program with 22 residents initially collected data daily for 4 weeks without PDA
      use. Data included preround time, check-out time, total number of patients,
      number of medical/surgical patients, and number of intensive care unit patients.
      The definition of prerounding time was started when residents first began
      collecting information on their patients in the morning until 6:00 am. Check-out
      time started at 5:00 pm and lasted until the discussion of patient care with the
      night team had finished. Residents were then given PDAs allowing immediate up-to
      date access to patient information, which most importantly included current vital
      signs, laboratory data, radiological dictations, medication lists, and fluid
      intake and output. After a 4-week acquaintance period with the PDA had passed,
      data were again collected from the residents daily for 4 weeks. Daily averages
      for each week and an overall total average were calculated. Daily averages were
      also calculated for each PGY level. Paired t-tests compared the pre-PDA and post
      PDA total averages. RESULTS: No significant difference was found between the
      total number of patients pre-PDA and post-PDA (7.6 and 7.6, respectively, p =
      0.98), the average number of medical/surgical patients (4.7 and 7.1,
      respectively, p = 0.16), or the average number of intensive care unit patients
      (2.6 and 0.4, respectively, p = 0.06). Also, no significant difference was found
      between pre-PDA and post-PDA with average check-out time (24.5 minutes and 21.9
      minutes, respectively, p = 0.06). However, a significant decrease in rounding
      time occurred with pre-PDA round time at 50.5 minutes and post-PDA round time at
      40.7 minutes (p = 0.02). CONCLUSION: Results of this study support the hypothesis
      that the prerounding time dramatically decreases with the PDA compared to
      without. Not only does this decrease in time help to keep residents under the 80
      hour work week rule, but also it helps to eliminate much of the confusion that
      can cause patient safety issues.

PMID- 18063270
TI  - Effect of the 30-hour work limit on resident experience and education.
AB  - PURPOSE: To evaluate the effect of the 30-hour restriction on resident operative
      participation and assess whether the 30-hour restriction can be extended in
      certain cases to enhance educational experience and continuity of care without
      being detrimental to the 80-hour limit. METHODS: In September 2006, we
      administered a 10-item Likert scale survey to 41 general surgery residents to
      assess their experience with the 30-hour work restriction. We also reviewed the
      operative reports from the busiest general surgery service in April 2003 and
      April 2005 to assess surgical participation before and after the 30-hour
      restriction. RESULTS: Twenty-three (56%) residents reported missed operations
      each month because of the 30-hour restriction. Thirty-four (83%) reported
      occasions where participating in an operation would require only an additional 1
      4 hours. Thirty-six (88%) residents reported a better educational experience when
      operating on patients whom they had evaluated and a preference to operate on
      patients whom they had evaluated. The operative log review revealed that in April
      2003, the resident assigned to the service participated in 47 out of 134 (35%)
      total operations and 11 out of 30 (37%) operations beginning after noon. In April
      2005, the resident assigned to the service participated in 49 out of 109 (45%)
      total operations and 20 out of 45 (44%) of the operations beginning after noon.
      CONCLUSION: The difference in the amount of operations involving resident
      participation before and after the 30-hour restriction, including afternoon cases
      that would be most affected by the work restriction, was minimal. However, we
      identified occasions when the 30-hour work restriction could be extended to
      provide continuity of care and a better educational operative experience while
      maintaining weekly duty hours within the approved limit. Extensions beyond the 30
      hours should be limited to providing unique and comprehensive experiences for
      residents where the additional time or episodes would not cause resident fatigue.

PMID- 18063271
TI  - Face, content, and construct validities of inanimate intestinal anastomoses
      simulation.
AB  - PURPOSE: Surgical simulation modules for "open" surgery are limited and not well
      studied or validated. Available simulation modules use either synthetic material,
      which is convenient but may not mimic what is observed or felt in the operating
      room, or live animal laboratories, which can simulate human tissue but are costly
      and not readily available. An intestinal anastomosis simulation was devised with
      thawed porcine intestine. In this study, the face, content, and construct
      validities of this simulation module were analyzed for both hand-sewn and stapled
      anastomoses. METHODS: Participants were timed on performing a 2-layered, hand
      sewn anastomosis, as well as a side-to-side, functional, end-to-end, stapled
      anastomosis on thawed porcine small bowel. Anastomoses were examined for adequacy
      and measured for luminal narrowing and bursting pressure by intraluminal saline
      infusion. Questionnaires were answered regarding impressions with the simulation
      modules. Face, content, and construct validities were evaluated by comparing
      junior residents to senior residents and faculty. Data collected were analyzed
      with 2-sample t-tests. RESULTS: Both hand-sewn and stapled anastomoses showed
      strong face and content validity. Overall impressions of these inanimate
      simulation modules were a positive experience as reflected by the comments of
      participants. For hand-sewn anastomoses, a significant difference was found
      between junior and senior group times (50.0 +/- 17.2 vs 33.0 +/- 9.7 minutes, p =
      0.013) as well as PGY-1 and faculty times (64.0 +/- 7.2 vs 28.0 +/- 3.8 minutes,
      p = 0.001). Bursting pressures varied between both groups and were not
      significant. For stapled anastomoses, no difference was noted between the various
      groups in completion time or bursting pressure. CONCLUSIONS: Hand-sewn and
      stapled inanimate intestinal anastomoses are a valid simulation of intraoperative
      experience based on the face and content validities. Although stapled anastomosis
      does not have good construct validity, the more challenging hand-sewn anastomosis
      does differentiate between various skill levels.

PMID- 18063273
TI  - Importance of the faculty interview during the resident application process.
AB  - OBJECTIVES: Selection of surgical residents is accomplished by processes unique
      to each institution based on anecdotal observations, self-evident truisms, and
      programmatic objectives. By closely examining how surgical residents are
      selected, we sought to determine whether this process accurately predicted
      exceptional clinical performance of matriculated residents. DESIGN: Retrospective
      correlation of applicant composite scoring system with the core competency-based
      clinical rotation performance ratings as well as the final match rank list.
      SETTING: University-based surgery residency program. PARTICIPANTS: Residency
      applicants, residents, and faculty. RESULTS: Applicant personal characteristics
      (PCs) and reference letter quality (RL) assessed during faculty interviews
      correlated most strongly with subsequent clinical performance, whereas medical
      school academic records (GPA) and USMLE scores correlated negatively. Faculty
      concern for resident performance also correlated negatively with PC (-0.55) and
      RL (-0.44) but positively with USMLE (r = 0.47) and GPA (r = 0.39). Residents who
      required remediation during training actually carried higher USMLE (236 vs 224, p
      < 0.05) and GPA (4.5 vs 4.0, p < 0.05). Both USMLE and GPA correlated positively
      with ABSITE (0.44 and 0.35) and ABS Qualifying Exam (0.82 and 0.64) performance.
      The final match list correlated highly with PC (r = -0.74) and RL (r = -0.71),
      much more so than with GPA (r = -0.27) or USMLE scores (r = -0.22). Use of PC and
      RL, alone, correlated better with final ranking (r = -0.76) than did our previous
      10-component composite score (-0.60). Modification of interview invitation
      criteria was predicted to reduce by 80% the number of interviews for applicants
      ultimately not ranked. CONCLUSIONS: Compared with a previous 10-point composite
      scoring system, faculty evaluations of personal characteristics and letters of
      reference were likely to predict subsequent resident clinical performance. USMLE
      scores and academic grade performance were predictive of subsequent formalized
      testing such as ABSITE, but they were poorly predictive of resident clinical
      performance. The resident selection process can be streamlined.

PMID- 18063272
TI  - From the flight deck to the operating room: an initial pilot study of the
      feasibility and potential impact of true interdisciplinary team training using
      high-fidelity simulation.
AB  - BACKGROUND: The operating room is a dynamic environment in which proper teamwork
      is essential. After piloting a simulation-based interdisciplinary operative team
      training program, we examined the impact of these sessions on the participants.
      METHODS: Three interdisciplinary operating room teams participated in the
      training model. Each team of 3 or 4 members completed the training in a virtual
      minimally invasive operating room using a standardized operative scenario. Upon
      completion of the training, participants completed a voluntary and anonymous
      training effectiveness questionnaire. RESULTS: All 10 participants completed the
      training evaluation questionnaires. Across the 3 teams, all participants felt
      that the training was worthwhile and would participate again. Eight participants
      said that the session would change their practices in the operating room. All
      participants felt that the session was effective in promoting team communication
      skills and crisis-related teamwork. Nine of the 10 felt that the training model
      was effective in recognizing operating room errors. CONCLUSIONS: Implementing
      true interdisciplinary team training with a high-fidelity simulation can be
      accomplished effectively. Team training has the potential for facilitating
      positive behavioral changes in operating room personnel that are important for
      adaptive team function in a crisis situation.

PMID- 18063274
TI  - Learning styles vary among general surgery residents: analysis of 12 years of
      data.
AB  - PURPOSE: Understanding the learning styles of individuals may assist in the
      tailoring of an educational program to optimize learning. General surgery faculty
      and residents have been characterized previously as having a tendency toward
      particular learning styles. We seek to understand better the learning styles of
      general surgery residents and differences that may exist within the population.
      METHODS: The Kolb Learning Style Inventory was administered yearly to general
      surgery residents at the University of Cincinnati from 1994 to 2006. This tool
      allows characterization of learning styles into 4 groups: converging,
      accommodating, assimilating, and diverging. The converging learning style
      involves education by actively solving problems. The accommodating learning style
      uses emotion and interpersonal relationships. The assimilating learning style
      learns by abstract logic. The diverging learning style learns best by
      observation. Chi-square analysis and analysis of variance were performed to
      determine significance. RESULTS: Surveys from 1994 to 2006 (91 residents, 325
      responses) were analyzed. The prevalent learning style was converging (185, 57%),
      followed by assimilating (58, 18%), accommodating (44, 14%), and diverging (38,
      12%). At the PGY 1 and 2 levels, male and female residents differed in learning
      style, with the accommodating learning style being relatively more frequent in
      women and assimilating learning style more frequent in men (Table 1, p < or =
      0.001, chi-square test). Interestingly, learning style did not seem to change
      with advancing PGY level within the program, which suggests that individual
      learning styles may be constant throughout residency training. If a resident's
      learning style changed, it tended to be to converging. In addition, no relation
      exists between learning style and participation in dedicated basic science
      training or performance on the ABSIT/SBSE. CONCLUSIONS: Our data suggests that
      learning style differs between male and female general surgery residents but not
      with PGY level or ABSIT/SBSE performance. A greater understanding of individual
      learning styles may allow more refinement and tailoring of surgical programs.

PMID- 18063275
TI  - Multi-institutional validation of a web-based core competency assessment system.
AB  - OBJECTIVE: The Association of Program Directors in Surgery and the Division of
      Education of the American College of Surgeons developed and implemented a web
      based system for end-of-rotation faculty assessment of ACGME core competencies of
      residents. This study assesses its reliability and validity across multiple
      programs. METHODS: Each assessment included ratings (1-5 scale) on 23 items
      reflecting the 6 core competencies. A total of 4241 end-of-rotation assessments
      were completed for 332 general surgery residents (> or =5 evaluations each) at 5
      sites during the 2004-2005 and 2005-2006 academic years. The mean rating for each
      resident on each item was computed for each academic year. The mean rating of
      items representing each competency was computed for each resident. Additional
      data included USMLE and ABSITE scores, PGY, and status in program (categorical,
      designated preliminary, and undesignated preliminary). RESULTS: Coefficient alpha
      was greater than 0.90 for each competency score. Mean ratings for each competency
      increased significantly (p < 0.01) as a function of PGY. Mean ratings for
      professionalism and interpersonal/communication skills (IPC) were significantly
      higher than all other competencies at all PGY levels. Competency ratings of PGY 1
      residents correlated significantly with USMLE Step I, ranging from (r = 0.26, p <
      0.01) for Professionalism to (r = 0.41, p < 0.001) for Systems-Based Practice.
      Ratings of Knowledge (r = 0.31, p < 0.01), Practice-Based Learning & Improvement
      (PBLI; r = 0.22, p < 0.05), and Systems-Based Practice (r = 0.20, p < 0.05)
      correlated significantly with 2005 ABSITE Total Percentile. Ratings of all
      competencies correlated significantly with the 2006 ABSITE Total Percentile Score
      (range: r = 0.20, p < 0.05 for professionalism to r = 0.35, p < 0.001 for
      knowledge). Categorical and designated preliminary residents received
      significantly higher ratings (p < 0.05) than nondesignated preliminaries for
      knowledge, patient care, PBLI, and systems-based practice only. CONCLUSIONS:
      Faculty ratings of core competencies are internally consistent. The pattern of
      statistically significant correlations between competency ratings and USMLE and
      ABSITE scores supports the postdictive and concurrent validity, respectively, of
      faculty perceptions of resident knowledge. The pattern of increased ratings as a
      function of PGY supports the construct validity of faculty ratings of resident
      core competencies.

PMID- 18063276
TI  - Needlesticks and surgical residents: who is most at risk?
AB  - OBJECTIVE: Exposure to blood-borne diseases remains an occupational risk.
      Mandates have improved training in how to report exposures for all health-care
      workers. How exposure rates of surgical residents correlate with experience and
      mandatory training to reduce risk is not known. It was hypothesized that enhanced
      training would result in an increased reporting of exposures by surgical trainees
      and that risk would be greater in the first years of training. DESIGN:
      Retrospective review of occupational health records and operative case logs,
      prospective survey. METHODS: Occupational Health Services provides both initial
      and annual training to General Surgery house staff at the Medical College of
      Wisconsin. Initial training consists of a blood-borne pathogen review and a
      detailed explanation of exposure reporting. Mandatory annual training is provided
      during Surgical Grand Rounds. Training was enhanced beginning June 2005 using a
      videotape outlining surgical risks and specific countermeasures. The numbers of
      reported exposures per year before and after enhanced training were compared.
      Exposures were self-reported. As most exposures occurred in the operating room,
      rate of exposure was calculated for each year of training using the total number
      of cases done each year reported by the general surgical residents. RESULTS:
      Surgical residents reported 118 needlestick injuries over 6 years. Senior and
      chief residents demonstrated a significantly lower exposure rate than junior
      residents (nonparametric Mood's median test, p < 0.0001). No significant
      difference in the injury rate was found per 1000 cases after enhanced training.
      CONCLUSIONS: Increasing surgical experience lowered the needlestick injury rate.
      Assuming no change in self-reporting rates by year, enhanced training and
      reporting guidelines did not seem to change risk. More specific training for
      junior residents, as well as passive prevention solutions, may be necessary to
      positively impact their exposure risk.

PMID- 18063277
TI  - Resident training in flexible gastrointestinal endoscopy: a review of current
      issues and options.

PMID- 18063278
TI  - See one, do one, be competent in one? Resident rotations broaden the perceived
      scope of general surgery.
AB  - PURPOSE: To compare the scope of general surgery as perceived by general surgery
      program directors (PDs) nationally and our residents (RES), and to assess the
      effect of clinical rotation assignments on resident perception. METHODS: A
      background questionnaire and survey document drawn from the Resident Operative
      Report submitted by finishing residents to the American Board of Surgery (ABS)
      was sent to our general surgery residents. Respondents categorized 309 items as
      procedures with which a finishing resident should be competent (A), familiar (B),
      or neither (C). Data from an identical survey of PDs were obtained from the ABS.
      Procedures were assigned to Groups 1-4 based on resident rotations. PD responses
      were considered the reference data set. RES answers outside the range of 0.5x to
      1.5x, where x = PD% for each item, were labeled as different. Differences were
      categorized as residents having a "narrower" perception of general surgery if RES
      %A less than 0.5x and %C greater than 1.5x and "broader" if RES %A greater than
      1.5x and %C less than 0.5x. Chi-square testing was also performed as a "cross
      check" analysis. RESULTS: After eliminating consensus items, 60 Group 1 items,
      103 in Group 2, 19 in Group 3, and 16 in Group 4 remained. When linked to
      resident rotations, RES took a broader view of general surgery scope for 27/163
      items and a narrower view for only 1 item (0.6%). Without related rotation
      experience, RES viewed 0/19 procedures more broadly than PD and categorized 7/19
      items more narrowly. When items overlapped 2 surgical specialties, RES assigned
      no items as broader or narrower. Chi-square testing produced similar results.
      CONCLUSION: Our residents perceived the scope of general surgery more broadly
      than did a national sample of PDs for content areas in which residents completed
      rotations. A broader view of general surgery could influence resident decision
      making about postresidency fellowships.

PMID- 18063279
TI  - The effect of prior night call status on the American Board of Surgery in
      training examination scores: eight years of data from a single institution.
AB  - PURPOSE: Despite recent attention to resident duty hours, little data evaluate
      the effect of being on-call the night before taking an in-training examination on
      examination performance. The few previous studies evaluated single-year test
      scores, from heterogeneous cohorts, with inconsistent findings. The purpose of
      this study was to determine the effect of being on-call the night before taking
      the American Board of Surgery In-Training Examination (ABSITE) on resident scores
      at a single institution over a duration of several years. METHODS: Overall
      percentile rank, standard scores, and prior night call status were recorded for
      all residents (categorical and preliminary) taking the ABSITE at our institution
      from 1999 to 2006. A 2-way ANOVA was performed to determine whether (1) the
      standard scores varied significantly between residents not on-call and those who
      were on-call, 2) performance varied significantly by PGY level, and 3) there was
      a significant interaction between call status and PGY level. Percentile rank of
      residents on-call the night before the examination were compared with those off
      call using the Mann-Whitney U-test. For residents with scores from multiple
      years, standard scores from years on-call were compared with years off-call using
      the Wilcoxon signed rank test. RESULTS: A total of 282 ABSITE results were
      recorded with 69 (24%) residents taking in-house call the night before the
      examination. A 2-way analysis of variance indicated that although standard score
      performance varied significantly by PGY level (p < 0.001), no significant
      differences were found in scores at any PGY level attributable to being on-call
      (p = 0.70). This analysis was also performed on only categorical general surgery
      residents' scores. Again, no significant differences were attributable to being
      on-call. Similarly, a Mann-Whitney U-test indicated no statistical difference in
      percentile scores based on call status (p = 0.43). Matched resident scores from
      year to year did not differ significantly based on call status (p = 0.21).
      CONCLUSIONS: Based on several analytic models, being on-call the night before the
      ABSITE does not significantly affect resident performance.

PMID- 18063280
TI  - The impact of a formal minimally invasive service on the resident's ability to
      achieve new ACGME guidelines for laparoscopy.
AB  - PURPOSE: As laparoscopy continues to permeate general surgery, there is an
      increased need for residents to acquire advanced laparoscopic skills during a
      surgical training program. To underscore its importance, the Accreditation
      Council of Graduate Medical Education (ACGME) recently increased the requirements
      for laparoscopy from 34 to 60 basic cases and from 0 to 25 advanced cases. With
      this in mind, the purpose of this study is to assess the impact of an organized
      minimally invasive surgical service on the volume of advanced laparoscopic cases
      of a general surgery residency program. METHODS: In July 2005 an independent
      minimally invasive surgical service, consisting of a fellowship-trained
      laparoscopic surgeon and 3 general surgery residents was instituted in an
      otherwise stable academic general surgery residency program. A retrospective
      review of the general resident's operative database was performed from 2001 to
      2006 to assess the impact of this service on the volume of advanced laparoscopic
      cases of graduating chief residents. RESULTS: In the 4 years before the
      initiation of the minimally invasive service, the operative volume remained flat
      despite a stable training program and steady population growth. In the year after
      the formation of the dedicated service, the mean number of advanced cases
      performed by the graduating chief residents more than doubled, from 17.7 cases in
      each of the 2 years before, to 35.6 cases, fulfilling the ACGME requirements.
      CONCLUSION: The number of advanced laparoscopic cases per resident in this
      otherwise stable general surgery residency program substantially increased with
      the incorporation of a dedicated minimally invasive service led by a fellowship
      trained laparoscopic surgeon. These data suggest that the volume increases needed
      to satisfy ACGME requirements may only be possible by creation of such a training
      experience dedicated to advanced laparoscopy.

PMID- 18063281
TI  - Documenting a learning curve and test-retest reliability of two tasks on a
      virtual reality training simulator in laparoscopic surgery.
AB  - BACKGROUND: Virtual reality simulators are a component of the armamentarium for
      training surgical residents. No one knows exactly how to incorporate virtual
      reality simulators into a curriculum. The purpose of this study was to document
      and show the learning curve and test-retest reliability of 2 tasks on a virtual
      reality-training simulator (LapSim; Surgical Science, Goteborg, Sweden) in
      laparoscopic surgery. METHODS: Twenty-nine medical students participated in 8
      iterations of 7 virtual reality tasks ("camera navigation" (CN), "instrument
      navigation," "coordination," "grasping," "lifting and grasping" (LG), "cutting,"
      and "clip applying") Learning curves for each outcome variable of the CN and LG
      tasks were generated. Using ANOVA, we evaluated the differences between each
      score from attempt number 7 to attempt number 8 to document test-retest
      reliability. RESULTS: A plateau in the learning curve occurred within 8 sessions
      for CN misses, CN tissue damage, CN maximum damage, and LG maximum damage. Over
      the course of 8 sessions, a plateau in the learning curve was nearly reached for
      CN time, CN drift, CN path, CN angular path, and LG left and right path. The
      following variables had a downward trend to the mean learning curve over 8
      sessions, but they did not reach a plateau: LG time, LG left and right miss, LG
      left and right angular path, and LG tissue damage. CONCLUSION: Using the LapSim
      virtual reality simulator, we documented a learning curve and test-retest
      reliability for each outcome variable for CN and LG for rank novices. The
      modeling of the general learning curve is useful in designing training program.
      These results may be important in developing standards for technical evaluation
      in a surgical training curriculum.

PMID- 18063284
TI  - Comparison of genistein metabolism in rats and humans using liver microsomes and
      hepatocytes.
AB  - Species differences and metabolism are the most crucial factors in considering
      the effects of genistein. The aim of this study was to have a better knowledge of
      the metabolic fate of genistein in humans as compared with rats. For this
      purpose, radiolabeled genistein was incubated with human and rat liver microsomes
      and with cryopreserved hepatocytes from both species. Incubations were performed
      using a wide range of genistein concentrations to analyze the kinetics of
      formation of the metabolites. Metabolite profiling was obtained using an HPLC
      system connected to a radioactivity detector. Identification of the metabolites
      was based on their retention times as compared with those of authentic standards
      and on LC-MS (ESI-MS/MS) or NMR analyses. In both species, liver microsomes
      produced the same three hydroxylated metabolites (8-OH, 6-OH and 3'-OH-genistein)
      whereas cryopreserved hepatocytes produced the same glucurono- and sulfo
      conjugates (genistein 4'-O-sulfate 7-O-glucuronide, genistein 7-O-glucuronide,
      genistein 4'-O-glucuronide, genistein 7-O-sulfate and genistein 4'-O-sulfate).
      The rate of metabolism varied with species. 3'-Hydroxygenistein was the
      predominant metabolite produced by rat liver microsomes, whereas in humans 3'
      hydroxy and 8-hydroxygenistein were produced in the same range. In both human and
      rat hepatocyte incubations, genistein 7-O-glucuronide represented more than 50%
      of the incubated dose. Our results on hepatocytes confirmed the predominance of
      conjugation reaction compared to oxidative reaction observed in vivo.

PMID- 18063285
TI  - The role of lecithin cholesterol acyltransferase and organic substances from coal
      in the etiology of Balkan endemic nephropathy: a new hypothesis.
AB  - Balkan endemic nephropathy (BEN) occurs in Serbia, Bulgaria, Romania, Bosnia and
      Herzegovina, and Croatia. BEN has been characterized as a chronic, slowly
      progressive renal disease of unknown etiology. In this study, we examined the
      influence of soluble organic compounds in drinking water leached from Pliocene
      lignite from BEN-endemic areas on plasma lecithin-cholesterol acyltransferase
      (LCAT) activity. We found that changes for all samples were the most prominent
      for the dilution category containing 90% plasma and 10% of diluting media. Water
      samples from BEN villages from Serbia and Romania showed higher LCAT inhibiting
      activity (p=0.02) and (p=0.003), respectively, compared to deionised water and
      non-endemic water. A secondary LCAT deficiency could result from this inhibitory
      effect of the organic compounds found in endemic water supplies and provide an
      ethiopathogenic basis for the development of BEN in the susceptible population.

PMID- 18063286
TI  - Protective capacities of certain spices against peroxynitrite-mediated
      biomolecular damage.
AB  - Peroxynitrite, a potent cytotoxic agent, can damage a variety of biomolecules
      such as proteins, lipids, and DNA, and is considered as one of the major
      pathological causes of several diseases. Therefore, it would appear likely that
      interception of peroxynitrite by certain dietary compounds may represent one
      mechanism by which such foods may exert their beneficial action in vivo. A number
      of researchers have speculated that certain spices, rich in phenolics, may,
      conceivably, act as potential protectors against the actions of peroxynitrite.
      Eight culinary spices including cardamom, cinnamon, cloves, cumin, nutmeg,
      paprika, rosemary and turmeric were selected for study purposes. Further, the
      protective effects of methanol extracts of such spices against peroxynitrite
      mediated damage to proteins, lipids and DNA were evaluated as determined by these
      extracts' ability to attenuate the formation of, respectively, nitrotyrosine in
      albumin, thiobarbiturate acid-reactive substances (TBARS) in liposome and strand
      breakages for plasmid DNA. All of the tested spices exerted some level of
      protective ability against peroxynitrite-mediated biomolecular damage. Amongst
      them, cloves deserve special attention due to their outstanding protective
      abilities against two of three forms of peroxynitrite-mediated biomolecular
      damage. Additionally, the phenolic content of certain spices appears to correlate
      well with such spices' protective effect against peroxynitrite-mediated tyrosine
      nitration and lipid peroxidation. Such an observation indicates that phenolics
      present in the spices contributed to such spice-elicited protection against
      peroxynitrite toxicity.

PMID- 18063287
TI  - Integrated risk-benefit analyses: method development with folic acid as example.
AB  - With the introduction of novel and functional foods, there is increasing need for
      an integrated quantitative risk-benefit assessment of foods. Consensus about a
      quantitative risk-benefit assessment mirroring the risk assessment approach has
      been reached during a recent EFSA workshop. In line, we propose a risk-benefit
      model that consists of: (1) hazard and benefit identification, (2) hazard and
      benefit characterization through dose-response functions, (3) exposure
      assessment, and (4) risk-benefit integration. The DALY, which combines morbidity
      and mortality serves as common health measure. The overall health impact of bread
      fortified with folic acid in the Netherlands has been simulated. The case study
      showed how the risk-benefit approach may assist a policy maker in decisions on
      food fortification programs. It illustrates general problems regarding the data
      demands, the assumptions and uncertainties. A simple sensitivity analysis showed
      which assumptions were most crucial. Modest fortification (140 microg/100 g
      bread) seems reasonable to improve public health but the results hinge on the
      assumptions one makes for the association between colorectal cancer and high
      folate intake. A precautious policymaker may very well decide against folic acid
      fortification. The often debated increase in masked vitamin B(12)-deficiency
      appears negligible compared to the health gain resulting from prevented neural
      tube defects.

PMID- 18063288
TI  - [Efficacy of lipomodelling for the management of sequelae of breast cancer
      conservative treatment].
AB  - We report a study of 42 breast cancer patients undergoing lipomodelling, or fat
      transfer, for sequelae of conservative treatment. Detailed clinical and
      radiological data of the patients have been collected. These data demonstrate the
      feasibility of lipomodelling: the technique is simple but requires a learning
      curve to avoid cytosteatonecrotic lesions; the excellent results obtained in
      terms of shape and softness of the breast; no surgical implant or flap
      reconstruction is necessary; the reliability of the procedure: there is normal
      fat wasting within the first months after treatment, then results stabilize as
      the patient maintains a healthy weight; the small number of side-effects: only
      rare, predominantly infectious, rapidly resolving complications are induced. In
      conclusion, the fat transfer approach presented here represents a considerable
      advance for the management of moderate sequelae of conservative breast treatment.
      Using this technique makes it possible to restore the shape and softness of the
      breast better than any other surgical procedure before, particularly for patients
      with mild breast deformity.

PMID- 18063289
TI  - Thyroid hormone status and pituitary function in adult rats given oral doses of
      perfluorooctanesulfonate (PFOS).
AB  - INTRODUCTION: Perfluorooctanesulfonate (PFOS) is widely distributed and
      persistent in humans and wildlife. Prior toxicological studies have reported
      decreased total and free thyroid hormones in serum without a major compensatory
      rise in thyrotropin (TSH) or altered thyroid gland histology. Although these
      animals (rats, mice and monkeys) might have maintained an euthyroid state, the
      basis for hypothyroxinemia remained unclear. We undertook this study to
      investigate the causes for the PFOS-induced reduction of serum total thyroxine
      (TT4) in rats. HYPOTHESES: We hypothesized that exposure to PFOS may increase
      free thyroxine (FT4) in the rat serum due to the ability of PFOS to compete with
      thyroxine for binding proteins. The increase in FT4 would increase the
      availability of the thyroid hormone to peripheral tissues for utilization,
      metabolic conversation, and excretion. We also hypothesized that PFOS does not
      directly interfere with the regulatory functions of the hypothalamic-pituitary
      thyroid (HPT) axis in rats. EXPERIMENTS: Three experimental designs were employed
      to test these hypotheses. (1) Female Sprague-Dawley (SD) rats were given a single
      oral dose of 15 mg potassium PFOS/kg body weight. At intervals of 2, 6, and 24h
      thereafter, measurements were made for serum FT4, TT4, triiodothyronine (TT3),
      reverse triiodothyronine (rT3), thryrotropin (TSH), and PFOS concentrations, as
      well as liver PFOS concentrations, UDP-glucuronosyltransferase 1A (UGT1A) family
      mRNA transcripts, and malic enzyme (ME) mRNA transcripts and activity. (2) To
      provide evidence for increased uptake and metabolism of thyroxine (T4), 125 I-T4
      was given to male and female SD rats by intravenous injection, followed in 2h by
      a single oral dose of 15 mg potassium PFOS/kg body weight. 125 I radioactivity
      was determined in urine and feces collected over a 24-h period and in serum and
      liver collected at 24h. (3) To assess the potentials effect of PFOS on the
      hypothalamic-pituitary-thyroid axis, over an 8-day period, groups of male SD rats
      were given PFOS (3mg/kg-d), propyl thiouracil (PTU, 10 microg/mL in water), or
      PTU and PFOS in combination, with controls receiving 0.5% Tween 20 vehicle. On
      days 1, 3, 7, and 8, TT4, TT3, and TSH were monitored. On day 8, pituitaries were
      removed and placed in static culture for assessment of thyrotropin releasing
      hormone (TRH)-mediated release of TSH. RESULTS: (1) PFOS transiently increased
      FT4 and decreased TSH within 6h, with values returning to control levels by 24h.
      TT4 was decreased by 55% over a 24-h period. TT3 and rT3 were decreased at 24h to
      a lesser extent than TT4. ME mRNA transcripts were increased at 2h and activity
      was increased at 24h. UGT1A mRNA transcripts were increased at 2 and 6h. (2) 125
      I decreased in serum and liver relative to controls and consistent with a
      reduction in serum TT4. Concomitantly, 125 I activity was increased in urine and
      feces collected from PFOS-treated rats. (3) During the 8 days of dosing with
      PFOS, TSH was not elevated in male rats, while TT4 and TT3 were decreased.
      Pituitary response to TRH-mediated TSH release was not diminished after 8-daily
      oral doses of PFOS. CONCLUSIONS: These findings suggest that oral dosing in rats
      with PFOS results in transiently increased tissue availability of the thyroid
      hormones and turnover of T4 with a resulting reduction in serum TT4. PFOS does
      not induce a classical hypothyroid state under dosing conditions employed nor
      does it alter HPT activities.

PMID- 18063290
TI  - Comparison of laparoscopic and abdominal hysterectomy in terms of quality of
      life: a systematic review.
AB  - The objective of this study was to investigate the randomized studies reporting
      on quality of life after laparoscopic hysterectomy as compared to abdominal
      hysterectomy. A systematic qualitative review was performed on published studies
      identified by the databases PubMed and EMBASE, as well as cross-references.
      Randomized clinical trials on laparoscopic versus abdominal hysterectomy were
      assessed for the methods in which studies reported on postoperative health or
      quality of life as an outcome measure. Study results were described
      qualitatively. Thirty papers, published between 1994 and 2004, were identified.
      Only seven studies, incorporating data on 1450 patients, reported on
      postoperative health or quality of life. Four of these studies used eight
      different validated quality of life questionnaires. Two of these four studies
      reported significant differences between the treatment groups, with better
      quality of life in the first 6 weeks after laparoscopic hysterectomy when
      compared to the abdominal approach. Although, the main reason for performing a
      laparoscopic hysterectomy instead of an abdominal hysterectomy is the improvement
      of quality of life, only a few studies have used this as an outcome measure. The
      data available show that laparoscopic hysterectomy performs equally or better in
      terms of postoperative health and quality of life in the first weeks after
      surgery. In the decision for an approach to hysterectomy, the advantage of better
      quality of life should be offset against the increased risk of complications in
      laparoscopic hysterectomy.

PMID- 18063291
TI  - Changing views on the goal of reproductive genetic counselling in Hungary.
AB  - Over the last few decades, the goal of genetic counselling has been interpreted
      as giving value-neutral information about the genetic risk, the genetic disorder,
      and screening, diagnostic or treatment possibilities in order to promote the
      autonomous decision-making of counsellees. Recently, however, the theoretical
      possibility and the practical necessity of this non-directive approach have been
      questioned, and redefinition of the objective of genetic counselling is required.
      In our paper, we intend to contribute to this clarification process by critically
      examining the views of Hungarian genetic counsellors on the objective of genetic
      counselling, and by exploring the expectations of the counsellees. Our ethical
      analysis has revealed that counsellors supported divergent counselling goals,
      such as preventing diseases by giving direct recommendations, promoting the
      autonomous decision-making of clients by providing value-neutral information and
      facilitating careful deliberation by actively taking part in the resolution. The
      self-administered survey conducted among 170 counsellees has discovered that the
      majority of the respondents expected detailed information (98%), psychological
      support (68%), the counsellor's help in making decisions (68%), and the
      possibility of control over the resolution process (92%). The need to tailor help
      to individual clients has also been demonstrated, since a direct relationship was
      found between success in decision-making and whether unanswered questions
      remained or the calming effect of the consultation was felt. Of the methods
      proposed by the counsellors, the interpretive counselling approach promised
      fulfilment of the clients' wishes and respect for the accepted ethical norms;
      thus, teaching of this approach should be taken into consideration during the
      development of the post-graduate training curriculum for counsellors.

PMID- 18063292
TI  - Density functional theory study of N-H...O, O-H...O and C-H...O hydrogen-bonding
      effects on the 14N and 2H nuclear quadrupole coupling tensors of N-acetyl-valine.
AB  - Hydrogen-bonding effects in the crystalline structure of N-acetyl-valine, NAV,
      were studied using the (14)N and (2)H quadrupole coupling tensors via density
      functional theory. The calculations were carried out at the B3LYP level with the
      6-311++G(d,p) and 6-311+G(d) basis sets. The theoretical quadrupole coupling
      components and their relative orientation in the molecular frame axes at the
      nitrogen site are compared to experimental values. This nucleus is involved in a
      rather strong intermolecular O=CNH...O=CNH hydrogen bond, r(N-H...O(1))=2.04 A
      and angleN-H...O(1)=171.53 degrees. A reasonably good agreement between the
      experimentally obtained (2)H quadrupole coupling tensors and the B3LYP/6
      311++G(d,p) calculations is achievable only in molecular model where a complete
      hydrogen-bonding network is considered.

PMID- 18063293
TI  - A computational model for telomere-dependent cell-replicative aging.
AB  - Telomere shortening provides a molecular basis for the Hayflick limit. Recent
      data suggest that telomere shortening also influence mitotic rate. We propose a
      stochastic growth model of this phenomena, assuming that cell division in each
      time interval is a random process which probability decreases linearly with
      telomere shortening. Computer simulations of the proposed stochastic telomere
      regulated model provides good approximation of the qualitative growth of cultured
      human mesenchymal stem cells.

PMID- 18063294
TI  - Bacterial targeted tumour therapy-dawn of a new era.
AB  - Original observation of patients' spontaneous recovery from advanced tumours
      after an infection or a "fever" inspired extensive research. As a result, Coley's
      toxin for the therapy of sarcomas and live Bacillus Calmette-Guerin (BCG) for
      bladder cancer were born. In addition, three genera of anaerobic bacteria have
      been shown to specifically and preferentially target solid tumours and cause
      significant tumour lyses. Initial research had focused on determining the best
      tumour colonizing bacteria, and assessing the therapeutic efficacy of different
      strategies either as a single or combination treatment modalities. However,
      although clinical trials were carried out as early as the 1960s, lack of complete
      tumour lyses with injection of Clostridial spores had limited their further use.
      Recent progress in the field has highlighted the rapid development of new tools
      for genetic manipulation of Clostridia which have otherwise been a hurdle for a
      long time, such as plasmid transformation using electroporation that bore the
      problems of inefficiency, instability and plasmid loss. A new Clostridium strain,
      C. novyi-NT made apathogenic by genetic modification, is under clinical trials.
      New genetic engineering tools, such as the group II intron has shown promise for
      genetic manipulation of bacteria and forecast the dawn of a new era for a tumour
      targeted bacterial vector system for gene therapy of solid tumours. In this
      review we will discuss the potential of genetically manipulated bacteria that
      will usher in the new era of bacterial therapy for solid tumours, and highlight
      strategies and tools used to improve the bacterial oncolytic capability.

PMID- 18063295
TI  - Use of response surface methodology (RSM) in the evaluation of growth and
      copper(II) bioaccumulation properties of Candida utilis in molasses medium.
AB  - The influential factors on simultaneous growth and copper(II) bioaccumulation by
      growing cells of Candida utilis yeast under various ambient conditions, such as
      changing concentrations of molasses sucrose and copper(II) were tested. The
      highest growth rate of 0.133 h(-1) was obtained at an initial sucrose
      concentration of 15 g l(-1) in absence of copper(II). For each constant sucrose
      concentration chosen between 5 and 15 g l(-1), the increase in initial copper(II)
      concentration up to 500 mg l(-1) resulted in a decrease in the percentage uptake
      of copper(II) and moreover all copper(II) concentrations tested inhibited the
      yeast growth. On the other hand, at each constant copper(II) concentration
      studied, both the growth and copper(II) uptake yield enhanced with raising
      sucrose concentration up to 15 g l(-1). Maximum uptake yield of 34.2% was
      observed in 15 g l(-1) sucrose and 50 mg l(-1) copper(II) containing growth
      medium. The binary effects of initial sucrose and copper(II) concentrations on
      the specific growth rate and copper(II) uptake yield of yeast were analyzed by
      experimental design method and two model equations for predicting the growth rate
      and copper(II) uptake yield of yeast due to arbitrarily chosen sucrose and
      copper(II) concentrations were developed by using response surface methodology
      (RSM).

PMID- 18063296
TI  - Exposure profiles and source identifications for workers exposed to crystalline
      silica during a municipal waste incinerator relining period.
AB  - In this study, respirable crystalline silica exposures to furnace relining
      workers of 7 exposure groups were assessed by conducting personal respirable dust
      samplings. All possible pollutant sources were identified for each exposure group
      through field observations, and bulk samples were randomly collected from each
      identified pollutant source. All collected samples were analyzed for their
      tridymite, cristobalite, and quartz contents by using the X-ray diffraction
      method. Results show that quartz was the only detectable crystalline silica
      content. We found that the resultant respirable quartz exposure levels presented
      in sequence for the 7 exposure groups (sand blasting>bottom ash cleaning>wall
      demolishing>relining>others>grid repairing>scaffold establishing) were different
      from that of the corresponding respirable dust exposure levels (bottom ash
      cleaning>wall demolishing>sand blasting>relining>grid repairing>scaffold
      establishing>others). 87.3-100% of workers' respirable quartz exposures of the 7
      exposure groups exceeded the TLV-TWA (0.025 mg m(-3)) indicating appropriate
      control strategies should be taken immediately. By comparing the fractions of
      quartz contained in personal respirable dust samples with that contained in all
      possible pollutant sources for each exposure group, this study identified main
      pollutant sources for each exposure group as: bottom ash cleaning and scaffold
      establishing: bottom ash; sand blasting: blasting sand; wall demolishing:
      refractory cement+wall ash; wall relining: refractory brick; grid repairing: wall
      ash+refractory cement; grid repairing: wall ash+refractory cement; others:
      blasting sand+bottom ash. Finally, effective control strategies were proposed for
      exposure reduction by using above information together with our field
      observations.

PMID- 18063297
TI  - Short- and long-term effects of temperature on the Anammox process.
AB  - The application of the Anammox process has been usually focused on the treatment
      of wastewater with temperatures around 30 degrees C in order to operate under
      optimum conditions. In this work, the feasibility of the application of the
      Anammox process at lower temperatures has been tested. First, the short-term
      effects of temperature on the Anammox biomass were studied using batch tests. An
      activation energy of 63 kJ mol(-1) was calculated and the maximum activity was
      found at 35-40 degrees C. Activity tests done at 45 degrees C showed an
      irreversible loss of the activity due to the biomass lysis. A SBR was operated at
      different temperatures (from 30 to 15 degrees C) to determine the long-term
      effects. The system was successfully operated at 18 degrees C but when
      temperature was decreased to 15 degrees C, nitrite started to accumulate and the
      system lost its stability. Adaptation of biomass to low temperatures was observed
      when the specific activities obtained during first batch tests are compared to
      those obtained during the operation of the SBR.

PMID- 18063298
TI  - Preparation and use of chemically modified MCM-41 and silica gel as selective
      adsorbents for Hg(II) ions.
AB  - Adsorbents for Hg(II) ion extraction were prepared using amorphous silica gel and
      ordered MCM-41. Grafting with 2-(3-(2-aminoethylthio)propylthio)ethanamine was
      used to functionalize the silica. The functionalized adsorbents were
      characterized by nitrogen adsorption, X-ray diffraction, 13C MAS NMR spectroscopy
      and thermogravimetric analysis. The adsorption properties of the modified silica
      gel and MCM-41 were compared using batch method. The effect of pH, stirring time,
      ionic strength and foreign ions were studied. The extraction of Hg(II) ions
      occurred rapidly with the modified MCM-41 and the optimal pH range for the
      extraction by the modified materials was pH 4-7. Foreign ions, especially Cl- had
      some effect on the extraction efficiency of the modified silica gel and the
      modified MCM-41. The adsorption behavior of both adsorbents could be described by
      a Langmuir model at 298 K, and the maximum adsorption capacity of the modified
      silica gel and MCM-41 at pH 3 was 0.79 and 0.70 mmol g(-1), respectively. The
      modified MCM-41 showed a larger Langmuir constant than that of the modified
      silica gel, indicating a better ability for Hg(II) ion adsorption. The results
      indicate that the structure of the materials affects the adsorption behavior.
      These materials show a potential for the application as effective and selective
      adsorbents for Hg(II) removal from water.

PMID- 18063299
TI  - Early events in 2,4,6-trinitrotoluene (TNT) degradation by porphyrins: binding of
      TNT to porphyrin by hydrophobic and hydrogen bonds.
AB  - The interaction of meso-tri(4-sulfonatophenyl)mono(4-carboxyphenyl) porphyrin
      (C1TPP) with 2,4,6-trinitrotoluene (TNT) has been explored by UV-vis and
      fluorescence spectroscopy. The influence of temperature on the interaction has
      also been studied. C1TPP binds to TNT at pH 7.0 at room temperature via 1.94
      kcal/mole hydrogen bonds with absorbance loss at 412-413 nm and the appearance of
      a new peak at 422-424 nm. The hydrogen binding of TNT to C1TPP was confirmed by
      the dissolution of the complex upon the addition of urea. Increasing the
      temperature results in the appearance of a new absorbance peak at 540 nm and
      absorbance loss at 515 nm with activation energy of 29.7 kcal/mole in the range
      of the hydrophobic bond energy. This suggests the hydrophobic bonding of TNT with
      the pyrrole nitrogens in the porphyrin. Increasing the concentration of the TNT
      in the solution quenches the fluorescence of the porphyrin following the Stern
      Volmer equation. The association constants calculated from absorbance and
      fluorescence are expectedly similar.

PMID- 18063300
TI  - The characterization of PCDDs, PCDFs and coplanar PCBs during the past 50 years
      in Gwangyang Bay, South Korea.
AB  - The PCDD/DFs and coplanar PCBs (co-PCBs) in sediment samples from Gwangyang Bay
      in South Korea was investigated. The total concentration of dioxins and their
      toxic equivalent quantity (TEQ; calculated with the WHO 2005 Toxic Equivalency
      Factors) value in the surface sediment of the outer site (261 pg g(-1) TOC, 4.4
      pg-TEQ g(-1)) were 3-fold higher than the inner site (90 pg g(-1) TOC, 1.1 pg-TEQ
      g(-1)) in the Bay. The dioxin in the sediment samples was found to come from a
      mixture of the impurities of pentachlorophenol (PCP), chloronitrofen (CNP) and
      combustion based on the result of hierarchical cluster analysis (HCA). These
      dioxin sources have been influenced by the characterization associated with this
      region which was both an agricultural-centered and industrial-centered area.
      According to principal component analysis (PCA) related to the Kow values for the
      congener-specific composition of co-PCBs in the sediment core, the Kanechlor (KC)
      500 and the atmospheric deposition were identified as the possible sources. The
      maximum burden in the sediment core was 1.3 kg for 1967-1974 and the total
      burdens of PCDD/DFs and co-PCBs in the sediment core were estimated to be 6.6 kg
      during the past 50 years. The cumulative burdens of dioxin are still increasing
      in Gwangyang Bay.

PMID- 18063301
TI  - Sorption kinetics and isotherm studies of a cationic dye using agricultural
      waste: broad bean peels.
AB  - In this paper, broad bean peels (BBP), an agricultural waste, was evaluated for
      its ability to remove cationic dye (methylene blue) from aqueous solutions. Batch
      mode experiments were conducted at 30 degrees C. Equilibrium sorption isotherms
      and kinetics were investigated. The kinetic data obtained at different
      concentrations have been analyzed using pseudo-first-order, pseudo-second-order
      and intraparticle diffusion equations. The experimental data fitted very well the
      pseudo-first-order kinetic model. Analysis of the temportal change of q indicates
      that at the beginning of the process the overall rate of adsorption is controlled
      by film-diffusion, then at later stage intraparticle-diffusion controls the rate.
      Diffusion coefficients and times of transition from film to pore-diffusion
      control were estimated by piecewise linear regression. The experimental data were
      analyzed by the Langmuir and Freundlich models. The sorption isotherm data fitted
      well to Langmuir isotherm and the monolayer adsorption capacity was found to be
      192.7 mg/g and the equilibrium adsorption constant Ka is 0.07145 l/mg at 30
      degrees C. The results revealed that BBP was a promising sorbent for the removal
      of methylene blue from aqueous solutions.

PMID- 18063302
TI  - Toxicity and biodegradability of imidazolium ionic liquids.
AB  - Several bioassays have been carried out to analyze the toxicity and
      biodegradability of several imidazolium ionic liquids (ILs) in aqueous phase. The
      synthetized compounds consist of an imidazolium cation with two alkyl
      substituents in positions 3 (R1) and 1 (R2) and a counter-ion. The alkyl
      substituent R1 has been fixed as a methyl group and the effect of the alkyl chain
      length (C1-C8) of the other substituent (R2) has been tested. Moreover, the
      influence of diverse counter-ions A- (Cl-, PF6, XSO4-) has been analyzed. Acute
      toxicity and EC50 values of each compound in the aqueous solution have been
      determined by using the Microtox standard procedure. Biodegradability of IL has
      been determined by measuring BOD5 of aqueous samples containing IL and/or D
      glucose and the IL residual content and/or d-glucose concentration after this
      assay. The viability of the microorganisms used in the BOD5 has been related to
      the ATP in the samples, measured by a bioluminescence assay. All the ILs tested
      were not biodegradable in the considered conditions. Besides, it was found that
      the shorter the chain length of side chain R2, the lower the toxic effect is. On
      the contrary, the anion has a little effect on the IL toxicity.

PMID- 18063303
TI  - Morphologic analysis of the neuromuscular development of the anorectal unit in
      fetal rats with retinoic acid induced myelomeningocele.
AB  - To investigate whether myelomeningocele (MMC) is associated with a global
      neuromuscular maldevelopment of the lower gastrointestinal (GI) tract and
      anorectum, the distribution and staining intensity of non-neuronal (alpha-smooth
      muscle-actin), neural crest cell (NCC, [Hoxb5]), and neuronal markers (PGP-9.5,
      synaptophysin, neurotubulin-beta-III) within the distal colon, rectum, and anal
      sphincters were analyzed by immunohistochemistry and Western blot in rat fetuses
      with retinoic acid (RA) induced MMC. At term (E22), no gross-morphological
      differences of the anorectal unit of OIL (n=21) MMC (n=31), and RA-exposed-non
      MMC (RA, n=19) fetuses were found. Smooth muscle cells were evenly distributed
      within the muscle layers of the rectum and the internal anal sphincter in OIL,
      MMC, and RA fetuses. Density and staining intensity of NCC and mature enteric
      neurons within the myenteric plexus of the distal colon and rectum and
      innervation pattern within anal sphincters in MMC fetuses were analogous to RA
      and OIL controls. Normal smooth muscle and myenteric plexus development of the
      rectum and normal innervation of the anal sphincters and pelvic floor suggests
      that MMC is not associated with a global neuromuscular maldevelopment of lower GI
      structures in this short-gestational model.

PMID- 18063304
TI  - P3a and P3b components associated to the neurocognitive evaluation of invalidly
      cued targets.
AB  - The present report focuses on evaluating the neurocognitive consequences of the
      correct or incorrect spatial prediction induced by a spatial cue. Positions in
      the vertical meridian were cued in order to evaluate the cognitive consequences
      in the processing of the validly (VC) or invalidly cued (IC) targets. The
      behavioural responses and the 64 EEG channel were recorded. The late endogenous
      event-related potential (ERP) induced by target stimuli in VC and IC targets were
      compared in voltage amplitude, voltage and current source density topographies.
      The P3a and a late positive complex, possibly P3b were increased in a
      statistically significant manner in the IC targets with regard to the VC targets.
      The previous result suggests that subjects prepare to accomplish the task upon
      specification of the cue, and when the IC target appeared it is treated as a low
      probability stimulus in a similar manner to deviant stimuli in odd-ball
      paradigms.

PMID- 18063305
TI  - Brain activities immediately after finding rare targets.
AB  - It is generally assumed that the prior knowledge about the frequency of the
      target occurrence would influence the identification of a stimulus. Nevertheless,
      whether this influence occurs immediately after finding a rare target is unknown
      as yet. To clarify this issue, Event-related brain potentials were recorded in
      the present study while subjects were presented with thousands of pictures and
      were required to indicate whether a categorical target such as a tool was in the
      display. The results showed that participants responded more quickly to the
      posttarget nontargets (PNTs, i.e. the nontargets that immediately followed the
      rare targets) than to the common nontargets (CNTs, i.e. the nontargets that did
      not immediately follow the rare targets). Compared with CNTs, PNTs elicited
      enhanced amplitudes at N1, N2, and parietal P2 components. Moreover, the N2
      latency was longer overall for PNTs than for CNTs. These results suggested that
      the prior knowledge did not affect observer's judgment immediately; instead, the
      event of finding a rare target strengthened the processing of PNTs.

PMID- 18063306
TI  - Differential localization of rat Eag1 and Eag2 potassium channels in the retina.
AB  - Despite of their wide expression in the brain, the precise neurophysiological
      role of rat Eag1 (rEag1) and Eag2 (rEag2) K(+) channels remains elusive. Our
      previous studies in hippocampal pyramidal neurons demonstrate a somatodendritic
      localization of rEag1 and rEag2 channels, suggesting that the two channel
      isoforms may contribute to setting the membrane excitability of somas and
      dendrites. Here, we aim to further characterize the cellular and subcellular
      localization patterns of rEag1 and rEag2 proteins by studying their laminar
      distribution in the retina. Confocal microscopic analyses of immunofluorescence
      data revealed that rEag1 and rEag2 K(+) channels exhibit distinct cellular
      expression pattern in the retina. rEag1 immunoreactivity was most prominent in
      the outer half of the inner plexiform layer, whereas strong rEag2 immunostain was
      found in the outer and inner segments of photoreceptor cells, the outer plexiform
      layer, and the inner nuclear layer. These results suggest that rEag1 and rEag2
      K(+) channels may play a significant role in the transmission of electrical
      signals along the retinal neuronal circuits. We also performed double-labeling
      experiments to demonstrate that rEag1 and rEag2 are predominantly expressed in
      the somatodendritic compartment of retinal neurons. In addition, we presented
      evidence suggesting that rEag1 channels may be expressed in the GABAergic
      amacrine cell. Finally, based on their different immunostaining patterns over the
      inner region of the retina, we propose that compared to rEag2, rEag1 expression
      encompasses a significantly broader range of the somatodendritic compartment of
      the retinal ganglion cell.

PMID- 18063308
TI  - Association of DRD4 and COMT polymorphisms with anger and forgiveness traits in
      healthy volunteers.
AB  - Although the biological basis of trait anger, anger expression, and forgiveness
      are not well understood, there has been growing evidence that anger-related
      dispositions are heritable and associated with genetic polymorphisms. The purpose
      of the present study was to investigate the possible relationship between anger
      and forgiveness traits and the dopamine receptor D4 (DRD4) and catechol-O
      methyltransferase (COMT) Val158 Met polymorphisms in healthy Korean subjects.
      Three hundred and thirty-five healthy college students were recruited, and the
      308 participants with a complete data set (184 males, 124 females) were included
      in the data analysis. DNA of the subjects was isolated from whole blood cells,
      and DRD4 variable number of tandem repeats and COMT Val158 Met polymorphisms were
      genotyped using polymerase chain reaction. Participants performed the State-Trait
      Anger Expression Inventory and Trait Forgivingness Scale measuring anger and
      forgiveness traits. The DRD4 2-repeat (2R) allele group had significantly lower
      anger in tendency and higher forgiveness traits than the 4R allele group in
      males. Our results provide evidence that the 2R allele of DRD4 in a Korean sample
      might have a different function from the 4R allele and a gender-specific role on
      anger-related traits. The COMT Val158 Met polymorphism had no significant
      relationship with anger and forgiveness traits. These findings suggest a possible
      relationship between anger expression styles and forgiveness traits and
      dopaminergic dysfunction.

PMID- 18063307
TI  - Depressive symptoms in patients with chronic hepatitis C are correlated with
      elevated plasma levels of interleukin-1beta and tumor necrosis factor-alpha.
AB  - Studies suggest that cytokines have a role in the biology of depression. In this
      study, we evaluated depression and cytokine levels in patients with and without
      chronic hepatitis C (HCV) to better assess how chronic infection alters cytokines
      levels and may contribute to depressive symptomotology. Twenty-three adults with
      (n=16) and without (n=7) HCV were recruited through the Portland VA Medical
      Center. Research participants were excluded for current substance abuse,
      psychotic disorder, liver cirrhosis, or interferon (IFN) therapy. Participants
      completed the Beck Depression Inventory-II (BDI-II) and a blood draw to evaluate
      plasma cytokine levels [i.e., interleukin (IL)-1beta, IL-10 and tumor necrosis
      factor (TNF)-alpha]. t-Tests were performed to compare cytokine levels in
      patients with or without HCV. HCV patients showed higher TNF-alpha values
      compared to patients without HCV (group means=7.94 vs. 3.41pg/mL, respectively,
      p=0.047). There were no significant differences between the groups for the other
      cytokines assessed. In patients with HCV, TNF-alpha and IL-1beta levels (but not
      IL-10) were correlated with BDI-II scores [r=0.594, p=0.020 and r=0.489, p=0.055
      (trend), respectively]. Taken together, these results show an association between
      severity of depressive symptoms and expression of pro-inflammatory cytokines in
      patients with HCV. Future studies should investigate how inflammatory mediators
      play a role in the expression of specific depressive symptoms in patients with
      chronic infection. Patients with HCV represent an interesting model to examine
      this relationship.

PMID- 18063309
TI  - Topiramate reduces non-convulsive seizures after focal brain ischemia in the rat.
AB  - Acute "silent" seizures after brain injury are associated with a worsening of
      patient outcome and are often refractory to anti-epileptic drug (AED) therapy. In
      the present study we evaluated topiramate (TPM, 1-30 mg/kg, i.v.) in a rodent
      model of spontaneous non-convulsive seizure (NCS) activity induced by focal
      cerebral ischemia. For seizure detection, electroencephalographic (EEG) activity
      was continuously recorded for 24h in male Sprague-Dawley rats subjected to
      permanent middle cerebral artery occlusion (MCAo). Infarct volume, neurological
      deficit, and NCS were evaluated by an experimenter blinded to the treatment
      group. All vehicle treated rats (7/7) exhibited NCS following MCAo. TPM
      treatment, delivered at 20 min post-occlusion and prior to onset of NCS activity,
      dose-dependently reduced the incidence of NCS (ED(50)=21.1mg/kg). The highest
      dose of TPM tested (30 mg/kg) exhibited maximal reductions of 76% in the number
      of NCS/rat (vehicle=22.1+/-5.3, TPM=4.4+/-3.2, P<0.05), 80% in the total time of
      NCS (vehicle=1259+/-337 s, TPM=253+/-220 s, P<0.05), 20% in core brain infarction
      (vehicle=45+/-1%, TPM=36+/-4%, percent of ipsilateral volume corrected for
      swelling, P<0.05), and 38% in neurological deficit score (vehicle=7.4+/-1.2,
      TPM=4.6+/-1.5, P<0.05). Despite efficacy as a pre-seizure treatment, TPM was not
      effective when delivered immediately following onset of the first NCS event (36+/
      5 min post-MCAo). In conclusion, TPM exhibited significant efficacy for the
      prophylactic treatment of brain-injury induced NCS and represents a novel class
      of AED for treatment of this type of silent brain seizure.

PMID- 18063310
TI  - Attempting to solve the problem of pain: a questionnaire study in acute and
      chronic pain patients.
AB  - When faced with the problem of pain one can attempt a solution aimed at relief
      (assimilation) or a solution aimed at acceptance (accommodation). Using this dual
      process model of adaptation to pain, this study compares acute and chronic pain
      patients on their approach to problem solving. Three hundred and sixty-four
      patients were recruited from clinical settings, 303 with chronic pain and 61 with
      acute pain, and completed a range of measures of both affect and pain-related
      behavior, including the Pain Solutions Questionnaire. The effects of overall
      duration of pain were also investigated. Chronic pain patients reported greater
      disability and catastrophic thinking about pain than acute pain patients, and
      assimilative coping was associated with greater disability, greater attention to
      pain, and more catastrophic thinking about pain, beyond the effects of
      demographic variables and pain severity. Pain duration did not moderate these
      associations. Only in the case of catastrophic thinking about pain was it found
      that the effects of assimilative coping were moderated by pain duration. For
      chronic pain patients, catastrophic thinking about pain was greater when
      assimilative coping was higher. These results are discussed within the context of
      a goal directed motivational model of adaptation to chronic pain.

PMID- 18063311
TI  - Is it better to have controlled and lost than never to have controlled at all? An
      experimental investigation of control over pain.
AB  - Trying to control pain is a common human goal. But little is know about what
      happens when one loses control over pain. This paper reports an experiment with
      74 healthy volunteers, half of whom were given control over a pain stimulus and
      subsequently lost control, and half of whom never had control over the pain. This
      study investigates whether having had control and lost it would result in a more
      unpleasant pain experience, more fear about impending pain, a heightened
      vigilance to pain, and greater interference on a secondary task. Participants in
      the experimental group first learned to avoid a painful stimulus by correctly
      responding to a card sorting task, but later on lost control over the painful
      stimulus. In the yoked comparison group, participants had no control over the
      painful stimulus from the beginning. Results indicated that losing control over
      pain and, relatedly, attempting to control uncontrollable pain have significant
      costs such as a higher fear of the impending pain stimulus and retarded
      performance on a secondary task. When attempts to avoid pain are blocked,
      individuals persist in their avoidance attempts, try harder, and narrow their
      focus of attention upon the problem to be solved. These findings are discussed
      within the context of a dual process model of coping with uncontrollable adverse
      events [Brandtstadter J, Renner G. Tenacious goal pursuit and flexible goal
      adjustment: explication and age-related analysis of assimilative and
      accommodative strategies of coping. Psychol Aging 1990;5:58-67] and possible
      mechanisms for perseverance with ineffective solutions.

PMID- 18063312
TI  - Localization of S100A8 and S100A9 expressing neutrophils to spinal cord during
      peripheral tissue inflammation.
AB  - Investigation of hyperalgesia at the spinal transcriptome level indicated that
      carrageenan-induced inflammation of rat hind paws leads to a rapid but sustained
      increase in S100A8 and S100A9 expression, two genes implicated in the pathology
      of numerous inflammatory diseases including rheumatoid arthritis and gout. In
      situ hybridization revealed that the elevation occurred in neutrophils that
      migrate to the spinal cord vasculature during peripheral inflammation, not in
      spinal neurons or glial cells. Immunohistochemical analysis suggests, but does
      not prove, that these neutrophils abundantly release S100A8 and S100A9.
      Consistent with this, we detected an increase in ICAM and VCAM, both indicators
      of endothelial activation, a known trigger for secretion of S100A8 and S100A9.
      Migration of S100A8- and S100A9-expressing neutrophils to spinal cord is
      selective, since MCP-1- and CD68-expressing leukocytes do not increase in spinal
      cord vasculature during hind paw inflammation. Examination of many neutrophil
      granule mediators in spinal cord indicated that they are not regulated to the
      same degree as S100A8 and S100A9. Neutrophil migration also occurs in the
      vasculature of brain and pituitary gland during peripheral inflammation.
      Together, these findings suggest an interaction between a subpopulation of
      leukocytes and the CNS during peripheral tissue inflammation, as implied by an
      apparent release and possible diffusion of S100A8 and S100A9 through the
      endothelial blood-brain barrier. Although the present findings do not establish
      the neurophysiological or behavioral relevance of these observations to
      nociceptive processing, the data raise the possibility that selective populations
      of leukocytes may communicate the presence of disease or tissue damage from the
      periphery to cells in the central nervous system.

PMID- 18063313
TI  - Taenia taeniaeformis: effectiveness of staining oncospheres is related to both
      temperature of treatment and molecular weight of dyes utilized.
AB  - Methods to determine viability of taeniid oncospheres following treatments with
      potential lethality have practical application in efforts to control
      transmission. Here we investigated several methods, in lieu of infectivity
      studies, to assess oncosphere viability and determine lethal temperature
      treatment regimens. In the first experiment, a standard treatment to exshell
      oncospheres with 0.5% hypochlorite was assessed for influence on oncosphere
      recovery of Taenia taeniaeformis eggs. Recovery of eggs and exshelled oncospheres
      decreased with increasing time in hypochlorite, which indicated that hypochlorite
      can damage eggs and oncospheres, translating into potential overestimation of
      lethality of experimental treatments. Losses in hypochlorite were accentuated
      when eggs were pretreated at 75 degrees C, but not lower temperatures, including
      65 degrees C, indicating a sharp threshhold between 65 degrees C and 75 degrees C
      where eggs and oncospheres became hypersensitive to subsequent hypochlorite
      treatment. To further investigate this change in relation to temperature, non
      vital (acridine orange, AO) and vital (propidium iodide, PI; trypan blue, TB)
      dyes were used to assess staining of oncospheres (exshelled or not) under
      conditions ranging from room temperature up to 95 degrees C. The behaviors of
      dyes as related to internal staining of oncospheres were described using non
      linear regression and a sigmoid four-parametric model to determine the inflection
      point (T50). Each of the dyes differed significantly in T50 estimates, e.g. AO
      (69.22+/-0.53), PI (73.89+/-0.52) and TB (79.43+/-0.45). For these dyes, the T50
      increased in relation to the increasing molecular weight of the dyes.
      Collectively, the results suggested that barriers to chemical permeability exist
      in eggs that breakdown incrementally with increasing temperatures above 65
      degrees C. This staining behavior and the likelihood that the temperatures
      involved are above a lethal threshhold clarify a basic limitation in the use of
      vital dyes to assess oncosphere viability. The results may be relevant to other
      Taenia spp.

PMID- 18063314
TI  - Dense transient receptor potential cation channel, vanilloid family, type 2
      (TRPV2) immunoreactivity defines a subset of motoneurons in the dorsal lateral
      nucleus of the spinal cord, the nucleus ambiguus and the trigeminal motor nucleus
      in rat.
AB  - The transient receptor potential cation channel, vanilloid family, type 2 (TRPV2)
      is a member of the TRPV family of proteins and is a homologue of the
      capsaicin/vanilloid receptor (transient receptor potential cation channel,
      vanilloid family, type 1, TRPV1). Like TRPV1, TRPV2 is expressed in a subset of
      dorsal root ganglia (DRG) neurons that project to superficial laminae of the
      spinal cord dorsal horn. Because noxious heat (>52 degrees C) activates TRPV2 in
      transfected cells this channel has been implicated in the processing of high
      intensity thermal pain messages in vivo. In contrast to TRPV1, however, which is
      restricted to small diameter DRG neurons, there is significant TRPV2
      immunoreactivity in a variety of CNS regions. The present report focuses on a
      subset of neurons in the brainstem and spinal cord of the rat including the
      dorsal lateral nucleus (DLN) of the spinal cord, the nucleus ambiguus, and the
      motor trigeminal nucleus. Double label immunocytochemistry with markers of
      motoneurons, combined with retrograde labeling, established that these cells are,
      in fact, motoneurons. With the exception of their smaller diameter, these cells
      did not differ from other motoneurons, which are only lightly TRPV2
      immunoreactive. As for the majority of DLN neurons, the densely-labeled
      populations co-express androgen receptor and follow normal DLN ontogeny. The
      functional significance of the very intense TRPV2 expression in these three
      distinct spinal cord and brainstem motoneurons groups remains to be determined.

PMID- 18063316
TI  - Dynamics of cortical theta activity correlates with stages of auditory avoidance
      strategy formation in a shuttle-box.
AB  - By comparing behavioral performance and cortical theta activity (4-8 Hz) on a
      trial by trial basis we examined how the different behavioral stages of tone
      induced avoidance learning in the shuttle-box may be distinguishable by theta
      power as a potential correlate of changing strategies of information processing.
      Electrocorticograms with pronounced theta content were recorded across the
      cortical surface of gerbils during avoidance learning and analyzed in each trial
      in conjunction with reaction times and unconditioned and conditioned responses.
      The focus of theta analysis in this paradigm with a 5-s delay between tone and
      foot-shock onsets was on the 14-s periods after hurdle crossing where feedback
      information from a trial is available. The strongest theta activity occurred in
      stage 1 of initial tone conditioning which was sharply reduced to a minimum
      during stage 2 of optimization of unconditioned escape responses from the foot
      shock. A few initial successful avoidance responses gave rise to a reversal of
      the decline of theta activity that later reached a second maximum. A systematic
      increase of theta activity during this stage 3 of avoidance conditioning was
      found for the occasional trials with unconditioned responses and not for the
      increasing number of conditioned responses suggesting that error processing is a
      major correlate of this new increase of theta power. After the second maximum the
      theta power slowly declined together with a further improvement of behavioral
      performance indicating that stage 4 of retrieval of the consolidated avoidance
      response was reached. The results suggest that behind a previously reported
      general trend of decreasing theta power with increasing performance in this
      paradigm there is a hidden microstructure of theta activity across trials which
      separates stages of avoidance conditioning and is partially mirrored by known
      changes of prefrontal dopamine release.

PMID- 18063315
TI  - Isolation rearing impairs wound healing and is associated with increased
      locomotion and decreased immediate early gene expression in the medial prefrontal
      cortex of juvenile rats.
AB  - In addition to its maladaptive effects on psychiatric function, psychosocial
      deprivation impairs recovery from physical illness. Previously, we found that
      psychosocial deprivation, modeled by isolation rearing, depressed immediate early
      gene (IEG) expression in the medial prefrontal cortex (mPFC) and increased
      locomotion in the open field test [Levine JB, Youngs RM, et al. (2007) Isolation
      rearing and hyperlocomotion are associated with reduced immediate early gene
      expression levels in the medial prefrontal cortex. Neuroscience 145(1):42-55]. In
      the present study, we examined whether similar changes in behavior and gene
      expression are associated with the maladaptive effects of psychosocial
      deprivation on physical injury healing. After weaning, anesthetized rats were
      subjected to a 20% total body surface area third degree burn injury and were
      subsequently either group or isolation reared. After 4 weeks of either isolation
      or group rearing (a period that encompasses post-wearing and early adolescence),
      rats were killed, and their healing and gene expression in the mPFC were
      assessed. Locomotion in the open field test was examined at 3 weeks post-burn
      injury. We found that: 1) gross wound healing was significantly impaired in
      isolation-reared rats compared with group-reared rats, 2) locomotion was
      increased and IEG expression was suppressed for isolation-reared rats during burn
      injury healing, 3) the decreased activity in the open field and increased IEG
      expression was greater for burn injury healing group-reared rats than for
      uninjured group-reared rats, 4) the degree of hyperactivity and IEG suppression
      was relatively similar between isolation-reared rats during burn injury compared
      with uninjured isolation-reared rats. Thus, in the mPFC, behavioral hyperactivity
      to novelty (the open field test) along with IEG suppression may constitute a
      detectable biomarker of isolation rearing during traumatic physical injury.
      Implications of the findings for understanding, assessing, and treating the
      maladaptive effects of psychosocial deprivation on physical healing during
      childhood are discussed.

PMID- 18063317
TI  - Brief family treatment intervention to promote aftercare among substance abusing
      patients in inpatient detoxification: transferring a research intervention to
      clinical practice.
AB  - Two earlier studies showed that a brief family treatment (BFT) intervention for
      substance abusing patients in inpatient detoxification increased aftercare
      treatment post-detox. BFT consisted of meeting with the patient and a family
      member with whom the patient lived to review aftercare plans for the patient. A
      phone conference was used when logistics prevented an in-person family meeting.
      Based on the earlier research results, we trained a newly hired staff person to
      continue providing BFT. We monitored key process benchmarks derived from the
      earlier research studies to ensure ongoing fidelity in delivering BFT. This
      method proved successful in transferring BFT from delivery in a research study to
      ongoing delivery in routine clinical practice after the research ended. It also
      ensured that a high proportion of patients had their families contacted and
      included in planning the patients' aftercare.

PMID- 18063318
TI  - An evolutionary approach to major histocompatibility diversity based on allele
      supertypes.
AB  - Human leukocyte antigens are traditionally classified by serologic or molecular
      techniques into a bewildering variety of alleles. It is generally believed that
      this allelic diversity is maintained by selection pressures for inbreeding
      avoidance and/or maximal immune system diversity. While the usual antigen-based
      classification of individual alleles may be most appropriate in the artificial
      situation of tissue transplantation, we hypothesize that a functional
      classification based on allele supertypes may represent a more biologically
      relevant way to view MHC diversity in the contexts of mate choice and disease
      pathogenesis. Furthermore, immune system diversity could be quantitatively
      estimated by calculating a Supertype Diversity Index (SDI) which is the number of
      different MHC supertypes possessed by an individual. This hypothesis generates a
      number of testable predictions. First, it predicts that a reduced inherited
      diversity of MHC allele supertypes may predispose to the development of
      malignancies because of a decreased native ability to present different tumor
      associated antigens. Furthermore, specific autoimmune diseases may be associated
      with the presence or absence of a particular MHC supertype rather than a
      particular MHC haplotype. In transplant medicine, it is possible that unmatched
      alleles may trigger a weaker foreign antigen response if they are matched by
      allele supertype. Finally, there have been several studies documenting
      dissortative mating in humans for dissimilar MHC alleles. We predict that natural
      selection should favor maximization of the heterozygosity of allele supertypes
      instead of the heterozygosity of individual alleles and that the previously
      observed dissortative mating may actually be an adaptive strategy to maximize
      allele supertype diversity.

PMID- 18063319
TI  - Gamma-vinyl GABA inhibits cocaine-triggered reinstatement of drug-seeking
      behavior in rats by a non-dopaminergic mechanism.
AB  - Relapse to drug use is a core feature of addiction. Previous studies demonstrate
      that gamma-vinyl GABA (GVG), an irreversible GABA transaminase inhibitor,
      attenuates the acute rewarding effects of cocaine and other addictive drugs. We
      here report that systemic administration of GVG (25-300 mg/kg) dose-dependently
      inhibits cocaine- or sucrose-induced reinstatement of reward-seeking behavior in
      rats. In vivo microdialysis data indicated that the same doses of GVG dose
      dependently elevate extracellular GABA levels in the nucleus accumbens (NAc).
      However, GVG, when administered systemically or locally into the NAc, failed to
      inhibit either basal or cocaine-priming enhanced NAc dopamine in either naive
      rats or cocaine extinction rats. These data suggest that: (1) GVG significantly
      inhibits cocaine- or sucrose-triggered reinstatement of reward-seeking behavior;
      and (2) a GABAergic-, but not dopaminergic-, dependent mechanism may underlie the
      antagonism by GVG of cocaine-triggered reinstatement of drug-seeking behavior, at
      least with respect to GVG's action on the NAc.

PMID- 18063320
TI  - Craving predicts time to cocaine relapse: further validation of the Now and Brief
      versions of the cocaine craving questionnaire.
AB  - BACKGROUND: The 10-item version of the cocaine craving questionnaire (CCQ-Brief)
      has not been validated in a mixed-gender sample, and predictive validity of the
      CCQ-Now and CCQ-Brief in terms of their relationship with cocaine relapse has not
      been demonstrated. OBJECTIVE: To further validate the CCQ-Brief in a mixed gender
      sample and to determine the predictive validity of the CCQ-Now and CCQ-Brief.
      METHOD: Seventy-two men and 51 women (Total N=123) seeking inpatient cocaine
      dependence treatment were administered assessments upon admission, and a
      prospective design was employed to assess cocaine relapse outcomes during a 90
      day follow-up period after discharge from inpatient treatment. Data were analyzed
      using Pearson's correlation, Cox proportional hazards regression, and multiple
      regression. FINDINGS: The CCQ-Brief demonstrated good internal consistency and
      construct and concurrent validity. Both the CCQ-Now and the CCQ-Brief summary
      scores predicted time to cocaine relapse. In addition, the anticipation of a
      positive outcome from cocaine use, and intent and planning to use cocaine
      subscales of the CCQ-Now also predicted time to cocaine relapse. CONCLUSIONS: The
      CCQ-Brief was found to be a reliable and valid measure in a mixed gender sample,
      and both the CCQ-Now and CCQ-Brief were predictive of cocaine relapse risk.
      Craving assessments that go beyond desire and take into account intent and
      planning to use cocaine and the patient's anticipation of a positive outcome from
      using cocaine are likely to provide a sensitive index of cocaine relapse
      susceptibility. However, fear of social and clinical consequences could impact
      accurate reporting of cocaine craving and intent to use cocaine.

PMID- 18063322
TI  - Neuropsychological predictors of clinical outcome in opiate addiction.
AB  - A growing literature supports a role for neurocognitive deficits such as impaired
      decision-making in the development and maintenance of addictive behaviour. On the
      basis of these findings, it has been suggested that measures of neurocognitive
      functioning may be applied to the task of predicting clinical outcome in drug
      addiction. This in turn may have relevance for differentiating treatment based on
      individual patient needs. To explore this hypothesis we obtained neurocognitive
      measures of planning, impulsivity and decision-making from 37 opiate dependent
      individuals within 6 weeks of starting a community drug treatment programme and
      we followed them up 3 months into the programme. Performance on two tests of
      decision-making, but not on tests of planning, motor inhibition, reflection
      impulsivity or delay discounting, was found to predict abstinence from illicit
      drugs at 3 months with high specificity and moderate sensitivity. In particular,
      two thirds of the participants performing normally on the Cambridge Gamble Task
      and the Iowa Gambling Task, but none of those impaired on both, were abstinent
      from illicit drugs at follow up. Other neuropsychological, psychiatric or
      psychosocial factors measured in this sample did not explain this finding. The
      results are discussed in terms of the brain circuitry involved and the potential
      implications for the planning of treatment services for opiate dependence.

PMID- 18063321
TI  - Non-medical use, abuse and dependence on prescription opioids among U.S. adults:
      psychiatric, medical and substance use correlates.
AB  - BACKGROUND: Non-medical use of prescription opioids carries risks including
      development of abuse/dependence. Such use may correlate with psychiatric,
      medical, and substance use characteristics. METHODS: Cross-sectional survey, the
      2002-2004 National Survey on Drug Use and Health. Respondents 18 years and older
      (n=91,823). Bivariate and multivariable associations were investigated. RESULTS:
      The prevalence of past-year non-medical use of prescription opioids was 4.5%. Of
      those with non-medical use, 12.9% met criteria for abuse/dependence. On
      multivariable analysis, past-year non-medical use was associated with panic (AOR
      1.2; 95% CI 1.04-1.5), depressive (AOR 1.2; 95% CI 1.01-1.5) and social
      phobic/agoraphobic symptoms (AOR 1.2; 95% CI 1.1-1.4). Among those with past-year
      non-medical prescription opioid use, those with abuse/dependence were more likely
      to have panic (AOR 1.7; 95% CI 1.2-2.4) and social phobic/agoraphobic symptoms
      (AOR 1.7; 95% CI 1.2-2.4). In addition, they were more likely to report fair/poor
      health (AOR 2.1; 95% CI 1.4-3.0), have misused another class of prescription
      medication (AOR 1.7; 95% CI 1.2-2.3), have used heroin (AOR 2.9; 95% CI 1.2-6.9)
      and initiated substance use before the age of 13 (AOR 4.7; 95% CI 1.1-19.9).
      CONCLUSIONS: Non-medical use of prescription opioids is common. Furthermore,
      nearly 13% of those with non-medical use meet criteria for abuse/dependence.
      Panic, social phobia and agoraphobia, low self-rated health status, and other
      substance misuse among those with non-medical use of prescription opioids should
      alert clinicians to screen for abuse and dependence.

PMID- 18063323
TI  - Selective iNOS inhibition reduces renal damage induced by cisplatin.
AB  - Cisplatin is a chemotherapeutic agent used in the treatment of several cancer
      tumors; however, nephrotoxicity has restricted its use. Reactive oxygen species
      and peroxynitrite, which is formed by the reaction between superoxide anion and
      nitric oxide (NO*), are implicated in cisplatin-induced nephrotoxicity. In
      contrast, both toxic and beneficial effects of NO* have been suggested in
      cisplatin-induced nephrotoxicity. Therefore, nowadays the role of NO* in this
      experimental model remains controversial. The aim of the present work was to
      elucidate the role of NO* in cisplatin-induced renal damage using N-[3
      (aminomethyl)benzyl]acetamidine (1400W), a selective and irreversible inhibitor
      of iNOS. The mRNA levels of iNOS were increased in cisplatin-treated rats. The
      administration of 1400W reduced the cisplatin induced histological damage, renal
      dysfunction (increase in proteinuria and kidney injury molecule expression and
      decrease in creatinine clearance), tubulointerstitial infiltration, oxidative
      stress (increase in renal malondialdehyde and inmmunostaining for 4-hydroxy-2
      nonenal) and nitrosative stress (immunostaining for 3-nitrotyrosine). In
      addition, the administration of 1400W was unable to modify systolic blood
      pressure in control rats. Our data demonstrate that selective iNOS inhibition
      reduces the cisplatin-induced nephrotoxicity and nitrosative stress which
      strongly suggest that in this experimental model (1) the NO* production is toxic
      and (2) iNOS is the main source of NO*.

PMID- 18063324
TI  - Effects of dystocia, fetotomy and caesarian sections on the liver enzymes
      activities and concentrations of some serum biochemical parameters in dairy
      cattle.
AB  - The aim of the present study was to determine the level of serum liver enzymes,
      triglyceride and some metabolites in cows with or without difficulties during
      parturition. The second goal was to compare between the possible effects of
      caesarian section and fetotomy on these parameters. A total number of 24 native
      breed cows at full term were included in this study. Out of them, 8 gave normal
      parturition, 16 cows were admitted with dystocia. The group of dystocia was
      subdivided into two groups; fetotomy (n=8) and caesarian (n=8) group. In the
      caesarian group, 4 cows were with uterine torsion. Five blood samples were
      collected from each cow: directly pre-partum, during and just after delivery and
      at, 24, 48 and 72 h post-partum. Serum samples were used for determination of
      aspartate amino transferase (AST), glutamate dehydrogenase (GLDH), gamma glutamyl
      transferase (gamma-GT), creatine phosphokinase (CK), glucose, total bilirubin,
      cholesterol and triglyceride. The results showed that AST, GGT, GLDH and CK
      activities were significantly increased in the group with caesarian sections due
      to uterine torsion than the control and fetotomy groups. There were insignificant
      changes in serum GGT and GLDH activities between control, fetotomy and dystocia
      group without uterine torsion at pre-partum and at 24 and 48 h post-partum. At 72
      h post-partum, there was a significant increase in GLDH activity without
      significant increase in serum GGT activity. The concentrations of cholesterol and
      triglycerides did not differ in cows with dystocia compared to normal cows. In
      conclusion, cattle subjected to caesarian section and especially those with
      uterine torsion are associated with hepatic dysfunction. On the other hand,
      fetotomy has no effect on hepatocellular damage. The type of parturition has no
      effect on the bilirubin, cholesterol and triglyceride concentrations just before
      parturition to the 3rd day post-partum. It is recommended to supply cows with
      liver supportive therapy after caesarian section with uterine torsion.

PMID- 18063325
TI  - Formulation and characterisation of beads prepared from natural cyclodextrins and
      vegetable, mineral or synthetic oils.
AB  - A continuous external shaking for 2.5 days of a mixture composed of alpha
      cyclodextrin (6%), soybean oil (19.6%) and water (74.4%) resulted in a calibrated
      lipid carrier namely bead with a high fabrication yield. The purpose of this work
      was to explore the possibility to substitute alpha-cyclodextrin by other natural
      cyclodextrins, i.e. beta- and gamma-cyclodextrin and then soybean oil by mineral
      (Primol) 352 and Marcol 82) or synthetic (Silicon 200) fluid 10, 50 or 100cSt)
      oils. Beads can be successfully prepared using Marcol 82 with alpha-cyclodextrin
      and Silicon 50 or 100cSt with gamma-cyclodextrin. The area inside
      oil/cyclodextrin/water ternary diagram corresponding to bead occurrence was
      superior for the Marcol 82/alpha-cyclodextrin couple compared to that observed
      with soybean oil/alpha-cyclodextrin couple. Only a few ratios of Silicon 50 and
      100cSt/gamma-cyclodextrin/water led to beads. The combinations which did not
      induce bead occurrence gave either emulsions, two non-miscible liquids or a solid
      mixture. Whatever the materials used, beads exhibited similarities: presence of a
      crystalline organisation and viscoelastic properties. Manufacturing process of
      paraffin- and silicon-based beads need further optimisation to increase
      fabrication yield and later on, to take advantages from the high stability of
      both oils for the formulation of drugs with beads.

PMID- 18063326
TI  - Solubilisation of drugs in worm-like micelles of block copolymers of ethylene
      oxide and 1,2-butylene oxide in aqueous solution.
AB  - Ethylene oxide and 1,2-butylene oxide were sequentially polymerised to form the
      diblock copolymer E13B10 (E=oxyethylene, B=oxybutylene, subscripts denote number
      average block lengths in repeat units). Dynamic and static light scattering over
      the temperature range 10-30 degrees C demonstrated a transition from compact
      (spheroidal) micelles to larger, more elongated (worm-like) micelles with
      temperature increase above a critical onset temperature of about 20 degrees C.
      Determination of the solubilisation capacity for griseofulvin, carbamazepine and
      spironolactone of dilute micellar solutions of this copolymer, together with
      those of E11B8 and E17B12 block copolymers (which also show the sphere-to-worm
      transition), allowed investigation of the influence on solubilisation
      characteristics of hydrophobic block length and temperature. The extent of
      solubilisation at 25 degrees C of the poorly water-soluble drug spironolactone
      increased linearly with increase of hydrophobic block length, attributable to a
      concomitant increase in the proportion of worm-like micelles in solution.

PMID- 18063327
TI  - Loading of curcumin into macrophages using lipid-based nanoparticles.
AB  - Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, Cm) is a
      natural compound which possesses antioxidant, anti-inflammatory and anti-tumor
      ability. Here, phospholipid vesicles or lipid-nanospheres embedding Cm (CmVe or
      CmLn) were formulated to deliver Cm into tissue macrophages through intravenous
      injection. Cm could be solubilized in hydrophobic regions of these particles to
      form nanoparticle dispersions, and these formulations showed ability to scavenge
      reactive oxygen species as antioxidants in dispersions. At 6h after intravenous
      injection in rats via the tail vein (2mg Cm/kg bw), confocal microscopic
      observations of tissue sections showed that Cm was massively distributed in cells
      assumed as macrophages into the bone marrow and spleen. Taken together, these
      results indicate that the lipid-based nanoparticulates provide improved
      intravenous delivery of Cm to tissues macrophages, specifically bone marrow and
      splenic macrophages in present formulation, which has therapeutic potential as an
      antioxidant and anti-inflammatory.

PMID- 18063328
TI  - Monte Carlo simulations of drug release from matrices with periodic layers of
      high and low diffusivity.
AB  - We have studied drug release from matrices with periodic layers of high and low
      diffusivity using Monte Carlo simulations. Despite the fact, that the
      differential equations relevant to this process have a form that is quite
      different from the classical diffusion equation with constant diffusion
      coefficient, we have found that the Weibull model continues to describe the
      release process as well as in the case of the "classical" diffusion controlled
      drug release. We examine the similarities and differences between release from
      matrices with periodic layers and matrices with random mixtures of high and low
      diffusivity area and show that the periodic geometrical arrangement of the low
      diffusivity areas has an influence in the release profile which is negligible for
      low diffusivity ratios, but becomes important in the case of high diffusivity
      ratios and for intermediate values of the periodic "length". Such an arrangement
      in periodic layers leads to Weibull exponent a which are lower than those of the
      corresponding random arrangement and exponents b which are higher than those of
      the random case.

PMID- 18063329
TI  - Antitumor, antioxidant and antimicrobial activities of Bersama engleriana
      (Melianthaceae).
AB  - The aim of this study was to evaluate the antitumor, antioxidant and
      antimicrobial activities as well as the phytochemical composition and the acute
      toxicity of the methanolic extracts from the roots (BER), stem bark (BEB), leaves
      (BEL) and wood (BEW) of Bersama engleriana. The crown gall tumor and DPPH radical
      scavenging assays were used to detect respectively the antitumoral and oxidant
      activities. Agar diffusion and liquid dilution were used for antimicrobial tests
      and the phytochemical assays were conducted according to Harbone methods. The
      single-dose oral toxicity test was performed in accordance with the OPPTS
      870.1100 and OECD 401 guidelines. The phytochemical tests indicated the presence
      of flavonoids, phenols, triterpenes and anthraquinones in all extracts.
      Pronounced tumor reducing activity was observed with the extracts from the roots
      (69.32%) and leaves (65.42%). The DPPH scavenging activity showed that the
      extract from the leaves was the most active with 93.71% inhibition rate at the
      1000 microg/ml. The results of antimicrobial activity showed that all tested
      extracts were active against all tested microbial species, including Gram
      positive, and negative bacteria, the two Candida species and mycobacteria. The
      MIC values obtained ranged from 9.76 to 156.25 microg/ml. Under the conditions of
      the studied toxicity, all extracts were found to be non-toxic. The overall
      results of this study indicates that the extracts from the roots, stem bark,
      leaves and wood have interesting antioxidant properties and represent a potential
      source of medicine for the treatment of infectious diseases and cancer.

PMID- 18063330
TI  - Evaluation of Senegalese plants used in malaria treatment: focus on Chrozophora
      senegalensis.
AB  - An ethnobotanical study was conducted in the Dakar area of Senegal to investigate
      the species used in the treatment of malaria. Seven plants are principally used:
      Cissampelos mucronata, Maytenus senegalensis, Terminalia macroptera, Bidens
      engleri, Ceratotheca sesamoides, Chrozophora senegalensis and Mitracarpus scaber.
      From a bibliographic study, it had been shown that the Cissampelos mucronata,
      Maytenus senegalensis and Terminalia macroptera have already been studied by
      several authors, and so only Bidens engleri, Ceratotheca sesamoides, Chrozophora
      senegalensis and Mitracarpus scaber were evaluated in the present study. For each
      plant, extracts were prepared with different solvents and tested in vitro on two
      chloroquine-resistant Plasmodium falciparum strains. Crude extracts from the
      leaves and the stems of Chrozophora senegalensis showed the best in vitro
      results. The IC(50) value of an aqueous extract of Chrozophora senegalensis was
      1.6 microg/ml without cytotoxicity. The in vivo antiplasmodial activity of
      Chrozophora extracts was determined by both the oral and the intraperitoneal
      ways. The stages of Plasmodium cycle targeted by Chrozophora were then studied in
      vitro. These results could justify the traditional use of this plant in malaria
      treatment.

PMID- 18063332
TI  - Setting standards: diabetes.

PMID- 18063331
TI  - In vivo assessment of antidiabetic and antioxidant activities of rosemary
      (Rosmarinus officinalis) in alloxan-diabetic rabbits.
AB  - Rosemary (Rosmarinus officinalis), used in traditional Turkish folk medicine for
      the treatment of hyperglycaemia, is widely accepted as one of the medicinal herb
      with the highest antioxidant activity. Accordingly, the present study was
      designed to investigate the possible actions of ethanolic extract of the leaves
      of Rosmarinus officinalis on glucose homeostasis and antioxidant defense in
      rabbits. In the first set of experiments, hypoglycaemic effects of oral
      administration of various doses (50, 100 and 200 mg/kg) of the extract were
      examined in normoglycaemic and glucose-hyperglycaemic rabbits. Optimal effect was
      observed in both of the animal groups with a dose of 200 mg/kg of the extract and
      this activity was independent from the effects of insulin. In another part of
      experiments, acute effect of various doses of the Rosmarinus officinalis extract
      on blood glucose and serum insulin levels was studied in alloxan-induced diabetic
      rabbits. Of the three doses of extract, the highest dose (200 mg/kg)
      significantly lowered blood glucose level and increased serum insulin
      concentration in alloxan-diabetic rabbits. The last set of experiments designed
      to investigate the subacute effect of the Rosmarinus officinalis extract on
      repeated administration in alloxan-diabetic rabbits. At the doses of 100 and 200
      mg/kg, antihyperglycaemic effect of extract was accompanied by a significant
      increase in serum insulin levels in diabetic rabbits. Furthermore, during 1 week
      of treatment of diabetic rabbits with a dose of 200 mg/kg of the extract showed
      that the extract possessed a capability to inhibit the lipid peroxidation and
      activate the antioxidant enzymes. It was concluded that probably, due to its
      potent antioxidant properties, the Rosmarinus officinalis extract exerts
      remarkable antidiabetogenic effect.

PMID- 18063333
TI  - Application of discriminant analysis to differentiate between incorporation of
      cocaine and its congeners into hair and contamination.
AB  - The requirement to differentiate between incorporation and external contamination
      of drugs into hair is undisputed, in particular when dealing with compounds which
      are administered by sniffing or inhalation (e.g. cocaine). With the aim of making
      this discrimination, hair samples from cocaine (COC) users (group IN) and seized
      cocaine samples (group OUT) were compared regarding the parameters
      benzoylecgonine (BZE), ecgonine methyl ester (EME), ecgonine (ECG),
      anhydroecgonine methyl ester (AEME), cocaethylene (CE) and norcocaine (NCOC).
      Since most of these compounds may be minor by-products of COC or be formed by
      biotransformation or chemical degradation, the stability of each substance was
      carefully examined. COC was found to be converted into significant amounts of
      BZE, EME and ECG even under mild extraction conditions, while traces of NCOC
      proved to be a ubiquitous by-product of COC. Cocaine positive hairs and seized
      cocaine samples (diluted to relevant concentrations) were equally preprocessed
      and analyzed by LC-MS-MS. Out of the metabolites listed above, NCOC, CE and AEME
      (each normalised to COC) were significantly increased in the incorporation group
      (i.e. hair samples from cocaine users). Based on this approach, a statistical
      discriminant analysis enabled us to make a prediction (and estimation of
      uncertainty) for each cocaine positive hair sample as to its likelihood of
      belonging to the group of cocaine users or of being contaminated.

PMID- 18063334
TI  - Molecular study of time dependent changes in DNA stability in soil buried
      skeletal residues.
AB  - In the past years, many publications about identification and sex-determination
      of dry human bones by means of DNA analysis have been published. However, few
      studies exist that investigate the potential use of DNA technique to determine
      the postmortem interval (PMI). In the present study we analyzed the rate of
      increasingly smaller fragments of chromosomal DNA and PMI. We examined DNA
      degradation in human bones with postmortem intervals ranging between 1 and more
      than 200 years that had been kept under comparable conditions concerning weather
      and soil. Following bone separation into the three different zones of interest of
      inner/middle/outer segments the quantity of total DNA was determined in each
      region. Subsequently, the degree of DNA fragmentation was estimated by searching
      for PCR products of defined size (150, 507 and 763 bp) with primers of the human
      specific multicopy beta-actin-gene. Concerning DNA quantity we detected a
      significant correlation between the zone of interest and the amount of DNA.
      However, there was no correlation between the amount of DNA and PMI. In contrast
      to this, analyzing DNA using PCR showed a significant inverse correlation between
      fragment length and PMI. Thus, postmortem DNA degradation into increasingly
      smaller fragments reveals a time-dependent process. It has the potential to be
      used as a predictor of PMI in human bone findings, provided that environmental
      conditions are known.

PMID- 18063335
TI  - [Capnocytophaga canimorsus meningitis].

PMID- 18063336
TI  - Validation study of a pulsed arterial spin labeling technique by comparison to
      perfusion computed tomography.
AB  - Abnormalities in cerebral blood flow (CBF) are believed to play a significant
      role in the development of major neonatal neuropathologies. One approach that
      would appear ideal for measuring CBF in this fragile age group is arterial spin
      labeling (ASL) since ASL techniques are noninvasive and quantitative. The purpose
      of this study was to assess the accuracy of a pulsed ASL method implemented on a
      3-T scanner dedicated to neonatal imaging. Cerebral blood flow was measured in
      nine neonatal piglets, the ASL-CBF measurements were acquired at two inversion
      times (TI) (1,200 and 1,700 ms), and CBF was measured by perfusion computed
      tomography (pCT) for validation. Perfusion CT also provided images of cerebral
      blood volume, which were used to identify large blood vessels, and contrast
      arrival time, which were used to assess differences in arterial transit times
      between gray and white matter. Good agreement was found between gray matter CBF
      values from pCT (76+/-1 ml/min per 100 g) and ASL at TI=1,700 ms (73+/-1 ml/min
      per 100 g). At TI=1,200 ms, ASL overestimated CBF (91+/-2 ml/min per 100 g),
      which was attributed to substantial intravascular signal. No significant
      differences in white matter CBF from pCT and ASL were observed (average CBF=60+/
      1 ml/min per 100 g), nor was there any difference in contrast arrival times for
      gray and white matter (0.95+/-0.04 and 0.99+/-0.03 s, respectively), which
      suggests that the arterial transit times for ASL were the same in this animal
      model. This study verified the accuracy of the implemented ASL technique and
      showed the value of using pCT to study other factors that can affect ASL-CBF
      measurements.

PMID- 18063337
TI  - Diffusion-weighted imaging features of brain in obesity.
AB  - PURPOSE: Obesity is characterized by an altered distribution of body fluid.
      However, distribution of fluid (extracellular/intracellular) in brain tissues has
      not been studied in obese subjects yet. The purpose of this study was to detect
      possible brain diffusion changes especially in satiety and hunger related centers
      in obese subjects by diffusion weighted imaging (DWI). METHODS: Conventional MRI
      and DWI of the brain was obtained from 81 obese patients (obese=68, morbid
      obese=13) and 29 age-matched, nonobese. The apparent diffusion coefficient (ADC)
      values were calculated in hypothalamus; amygdala; hippocampal gyrus; thalamus;
      insula; cingulate gyrus; orbitofrontal, dorsomedial and dorsolateral frontal,
      middle temporal and occipital cortex; cerebellum; midbrain and corpus striatum.
      RESULTS: The ADC values of hypothalamus, hippocampal gyrus, amygdala, insula,
      cerebellum and midbrain were significantly increased in patients (n:81) when
      compared to nonobese subjects. The ADC values of thalamus, hippocampal gyrus,
      amygdala, orbitofrontal, occipital, dorsolateral and middle temporal cortex,
      insula and midbrain were significantly increased in morbid obese when compared to
      nonobese subjects. The ADC values of orbitofrontal and occipital cortex were
      significantly higher in morbid obese than the values in the obese. The body mass
      index positively correlated with ADC values of amygdala, insula, orbitofrontal
      and middle temporal cortex. CONCLUSION: We observed increased ADC values of
      distinct locations related to satiety and hunger that suggest altered fluid
      distribution and/or vasogenic edema in obese subjects. Awareness of this
      abnormalities in brain tissue composition/function in obesity may contribute to
      better understanding of the underlying mechanisms.

PMID- 18063338
TI  - Phase preparation in steady-state free precession MR elastography.
AB  - Strain and motion measurements in balanced steady-state free precession (bSSFP)
      imaging require high magnetic field homogeneity. This requirement is due to the
      nonlinear signal response to spin phase variations in bSSFP. Here, a technique
      that utilizes background gradients for preparing strong in-plane spin phase
      variations is proposed. As a result, periodic patterns of increased motion
      sensitivity appear, which are interleaved with bands of low phase-to-noise ratio.
      Spatial filters commonly used in MR elastography (MRE) remove these bands and
      leave wave images equivalent to a uniform phase response in bSSFP-MRE. Since
      phase preparation gradients locally enhance motion sensitivity, the technique can
      be employed for selectively increasing the wave signal amplitude in MRE. The
      method is applied without the need for previous shimming, which reduces the
      examination time. In vivo phase prepared bSSFP-MRE is demonstrated in human liver
      and heart.

PMID- 18063339
TI  - Inverse polarization transfer for detecting in vivo 13C magnetization transfer
      effect of specific enzyme reactions in 1H spectra.
AB  - The wide chemical shift dispersion and long T(1) of (13)C have allowed
      determination of in vivo magnetization transfer effects caused by aspartate
      aminotransferase and lactate dehydrogenase reactions using (13)C magnetic
      resonance spectroscopy. In this report, we demonstrate that these effects can be
      observed in the proton spectra by transferring the equilibrium magnetization of
      (13)C via the one-bond scalar coupling between (13)C and (1)H using an inverse
      insensitive nuclei enhanced by polarization transfer-based heteronuclear
      polarization transfer method. This inverse method allows a combination of the
      advantages of the long (13)C T(1) for maximum magnetization transfer and the high
      sensitivity of proton detection. The feasibility of this in vivo inverse
      polarization transfer approach was evaluated for detecting the (13)C
      magnetization transfer effect of aspartate aminotransferase and lactate
      dehydrogenase reactions from a 72.5-microl voxel in the rat brain at 11.7 T.

PMID- 18063340
TI  - Self-referrals to the A&E department during out-of-hours: patients' motives and
      characteristics.
AB  - OBJECTIVE: To determine self-referrals' motives to visit the accident & emergency
      departments (AED) and to compare their characteristics to patients contacting the
      GP cooperative. METHODS: Postal questionnaires were send to AED self-referrals
      and logistic regression analysis was used to contrast self-referrals to patients
      contacting the GP cooperative. RESULTS: For a study population of 62,000, during
      4 months, 5547 contacts were registered with the GP cooperative, along with 808
      AED contacts, 344 of whom (43%) were self-referrals. Main reasons to visit the
      AED were the perceived need for diagnostic facilities and the conviction that the
      hospital specialist was best qualified to handle the problem. Dissatisfaction
      with the GP cooperative among respondents was high. Self-referral to the AED was
      positively associated with injury, age between 15 and 64, musculoskeletal,
      cardiovascular and respiratory problems, and distance to the GP centre.
      CONCLUSION: Self-referrals emerge as patients with a strong preference for the
      AED, mainly based on assumptions on quality of care and necessary facilities.
      PRACTICE IMPLICATIONS: While self-referrals may, in part, make motivated and
      appropriate choices to visit the AED, new integrated care models should be
      studied that can adequately deflect those who are eligible for GP care.

PMID- 18063341
TI  - [An unusual complication of ventral decubitus].

PMID- 18063342
TI  - P-glycoprotein-mediated efflux of phenobarbital at the blood-brain barrier
      evidence from transport experiments in vitro.
AB  - The purpose of the present studies was to investigate characteristics of
      phenobarbital (PB) transport across the blood-brain barrier (BBB). Cultured rat
      brain microvascular endothelial cells (rBMECs) were used as an in vitro BBB
      model. Experiments were conducted to examine time-, concentration- and
      temperature-dependent elements of PB uptake, and the effect of tested agents on
      the steady-state uptake of PB. PB efflux from rBMECs and the polarised transport
      of PB were examined to evaluate whether P-glycoprotein (P-gp) was involved in the
      PB efflux transport across BBB. The results demonstrated that the uptake of PB by
      rBMECs was in a time-, concentration- and temperature-dependent manner. P-gp
      modulators, cyclosporin A (CsA), ketoconazole and metabolic inhibitor
      dinitrophenol, increased the PB steady-state uptake by more than 50% (p < 0.01),
      and decreased the PB efflux by more than 50% (p < 0.01). Similar results were
      observed in the uptake and efflux studies of rhodamine-123 by co-administration
      of CsA. Further results were obtained in the polarised transendothelial transport
      of PB in the apical to basolateral (A-B) and basolateral to apical (B-A)
      directions either with or without CsA. The result showed that transport of PB in
      the B-A direction was significantly greater than the transport in the A-B
      direction (p < 0.05), and the co-administration of 50microM CsA almost inhibited
      P-gp-involved efflux in the rBMECs. Overall, these findings suggest that P-gp may
      contribute to the efflux transport of PB across BBB.

PMID- 18063343
TI  - Concordance of standard and modified NCEP ATP III criteria for identification of
      metabolic syndrome in outpatients with schizophrenia treated with antipsychotics:
      a corollary from the CLAMORS study.
AB  - OBJECTIVE: To analyze the concordance between standard and modified NCEP-ATP-III
      criteria for identification of metabolic syndrome (MS) in outpatients with
      schizophrenia. METHOD: We used the sample from a cross-sectional study carried
      out to ascertain the prevalence of MS in schizophrenia. Kappa agreement and the
      symmetry Kendall's tau-b coefficients were calculated in a post-hoc analysis, a
      long with McNemar test and logistic regression models. RESULTS: The study
      enrolled 1,452 consecutive outpatients. MS was found in 24.6% (95%CI: 22.4%
      26.8%) using the standard criteria and in 25.5% (23.2%-27.7%) using the modified
      criteria. Agreement was high; kappa 0.81 (p<0.0001) and tau-b 0.81 (p<0.0001),
      with a McNemar value of 0.2325. Kappa coefficients varied between 1.0 and 0.76 in
      subgroups according to sex, age-group, severity of disease, and duration of
      therapy. CONCLUSIONS: MS in outpatients with schizophrenia may be assessed by
      either the standard or the modified NCEP ATP III criteria without losing
      reliability.

PMID- 18063344
TI  - Reduced frontopolar activation during verbal fluency task in schizophrenia: a
      multi-channel near-infrared spectroscopy study.
AB  - Functional neuroimaging studies to date have shown prefrontal dysfunction during
      executive tasks in schizophrenia. However, relationships between hemodynamic
      response in prefrontal sub-regions and clinical characteristics have been
      unclear. The objective of this study is to evaluate prefrontal hemodynamic
      response related to an executive task in schizophrenia and to assess the
      relationship between activation in the prefrontal sub-regions and clinical
      status. Fifty-five subjects with schizophrenia and age- and gender-matched 70
      healthy subjects were recruited for this case-control study in a medical school
      affiliated hospital in the Tokyo metropolitan area, Japan. We measured hemoglobin
      concentration changes in the prefrontal (dorsolateral, ventrolateral, and
      frontopolar regions) and superior temporal cortical surface area during verbal
      fluency test using 52-channel near-infrared spectroscopy, which enables real-time
      monitoring of cerebral blood volumes in the cortical surface area under a more
      restraint-free environment than positron emission tomography or functional
      magnetic resonance imaging. The two groups showed distinct spatiotemporal pattern
      of oxy-hemoglobin concentration change during verbal fluency test. Schizophrenia
      patients were associated with slower and reduced increase in prefrontal
      activation than healthy controls. In particular, reduced activations of the
      frontopolar region, rather than lateral prefrontal or superior temporal regions,
      showed significant positive correlations with lower global assessment of
      functioning scores in the patient group, although task performance was not
      significantly associated with the scores. These results suggest that reduced
      frontopolar cortical activation is associated with functional impairment in
      patients with schizophrenia and that near-infrared spectroscopy may be an
      efficient clinical tool for monitoring these characteristics.

PMID- 18063345
TI  - Adapalene gel 0.1% is effective and safe for Japanese patients with acne
      vulgaris: a randomized, multicenter, investigator-blinded, controlled study.
AB  - BACKGROUND: Topical retinoids, such as adapalene, are an integral part of acne
      therapy in most regions and are considered appropriate first-line therapy by
      international guidelines for all cases of acne with the exception of the most
      severe. However, there are currently no topical retinoids available for the
      treatment of acne vulgaris in Japan. OBJECTIVE: To confirm efficacy and safety of
      adapalene gel 0.1% versus the corresponding gel vehicle in the treatment of
      Japanese patients with acne vulgaris for up to 12 weeks. METHODS: A total of 200
      patients were randomized to receive adapalene gel 0.1%, or vehicle once-daily for
      12 weeks. Percent reduction in lesion counts (total, inflammatory, and non
      inflammatory) and subject satisfaction were evaluated. Safety was monitored
      through adverse events and laboratory tests. RESULTS: Adapalene gel 0.1% produced
      significantly better reductions in total (P<0.0001), inflammatory (P=0.0010), and
      non-inflammatory lesions (P<0.0001) at endpoint (week 12, last observation
      carried forward) than gel vehicle, with a higher overall subject satisfaction.
      The primary efficacy variable, the median percent reduction of total lesion
      counts at endpoint, was significantly greater with adapalene gel 0.1% (63.2%)
      compared to that with the vehicle (36.9%) in the ITT population (P<0.0001).
      Significantly greater results were observed as early as week 1. Adapalene was
      well tolerated, with adverse events that were mostly mild-to-moderate and
      transient in nature. CONCLUSIONS: Adapalene gel 0.1% was effective in the
      treatment of acne vulgaris in Japanese patients. Adapalene was safe and well
      tolerated, consistent with the good tolerability profile demonstrated in other
      patient populations.

PMID- 18063347
TI  - The possible involvement of metabotropic glutamate receptors in schizophrenia.
AB  - Glutamate disruption is thought to have a major role in schizophrenia brain
      processes, possibly involving NMDA hypofunction. The metabotropic glutamate
      receptors are distributed in brain regions related to schizophrenia and seem to
      affect glutamate release in a moderate way. Compounds modulating these receptors
      are being investigated in animal models of schizophrenia, in an attempt to
      discover new antipsychotics. This article reviews the current research data
      regarding the role of these receptors in schizophrenia animal models. It was
      found that more research was done on Group I and II metabotropic receptors while
      investigation of group III receptors is still trailing behind. Accumulating
      evidence shows that mGluR5 antagonists by themselves do not necessarily disrupt
      pre-pulse inhibition (PPI), but can exacerbate disruption of PPI caused by MK-801
      and PCP, while positive modulation of this receptor has beneficial effects on
      these models of psychosis. Group II agonists are also showing beneficial effects
      in animal models. It seems that metabotropic glutamate receptor modulators could
      be developed into a novel treatment of schizophrenia by altering glutamate
      release, thus overcoming the putative NMDA hypofunction. Although the
      implications from these pre-clinical studies to human schizophrenia patients are
      premature, the data obtained with some compounds point to promising results for
      drug development. More studies, with agents active at other mGluRs in animal
      models and schizophrenia patients as well as with human subjects are needed in
      order to clarify the role of the metabotropic glutamate receptors in the
      pathophysiology and pharmacotherapy of schizophrenia.

PMID- 18063348
TI  - Cortical dopamine D(1) receptors in type 1 and type 2 alcoholics measured with
      human whole hemisphere autoradiography.
AB  - A large body of evidence indicates the importance of dopamine (DA) activation for
      ethanol reinforcement, and animal models of alcoholism have implied the
      involvement of DA D(1) receptors in this context. We studied cortical DA D(1)
      receptors in nine type 1 alcoholics (late-onset, binge-drinker), eight type 2
      alcoholics (early-onset, antisocial) and 10 controls by using [(3)H]SCH23390 as a
      radioligand in postmortem human whole hemisphere autoradiography. We also
      evaluated correlations of DA D(1) receptors between the cortical and subcortical
      areas and between cortical DA transporters and DA D(2) and D(3) receptors by
      comparing the present results to our earlier studies. On the average, type 2
      alcoholics were younger and had more violent causes of death than type 1
      alcoholics and controls. There were no statistically significant differences
      between the groups, suggesting that cortical DA D(1) receptors do not play a
      major role in alcoholism. However, among type 2 alcoholics, the binding was
      consistently lower (8.6%-22.3%) than among controls, and the effect sizes showed
      a large effect in the anterior cingulate (0.90) and frontal (0.87) cortices.
      Interestingly, among type 2 alcoholics, the correlation of DA D(1) receptors
      between two ventral midbrain structures (substantia nigra and amygdala) and
      anterior cingulate cortex was significantly negative, whereas in the type 1
      alcoholics and controls, the correlations were significantly positive.

PMID- 18063350
TI  - Aquaporin structure-function relationships: water flow through plant living
      cells.
AB  - Plant aquaporins play an important role in water uptake and movement-an aquaporin
      that opens and closes a gate that regulates water movement in and out of cells.
      Some plant aquaporins also play an important role in response to water stress.
      Since their discovery, advancing knowledge of their structures and properties led
      to an understanding of the basic features of the water transport mechanism and
      increased illumination to water relations. Meanwhile, molecular and functional
      characterization of aquaporins has revealed the significance of their regulation
      in response to the adverse environments such as salinity and drought. This paper
      reviews the structure, species diversity, physiology function, regulation of
      plant aquaporins, and the relations between environmental factors and plant
      aquaporins. Complete understanding of aquaporin function and regulation is to
      integrate those mechanisms in time and space and to well regulate the permeation
      of water across biological membranes under changing environmental and
      developmental conditions.

PMID- 18063349
TI  - Evidence for deficient modulation of amygdala response by prefrontal cortex in
      bipolar mania.
AB  - Several studies have implicated the involvement of two major components of
      emotion regulatory networks, the ventrolateral prefrontal cortex (VLPFC) and
      amygdala, in the pathophysiology of bipolar disorder. In healthy subjects, the
      VLPFC has been shown to negatively modulate amygdala response when subjects
      cognitively evaluate an emotional face by identifying and labeling the emotion it
      expresses. The current study used such a paradigm to assess whether the strength
      of this modulation was altered in bipolar subjects when manic. During functional
      magnetic resonance imaging (fMRI), nine manic subjects with bipolar I disorder
      and nine healthy subjects either named the emotion shown in a face by identifying
      one of two words that correctly expressed the emotion (emotion labeling task) or
      matched the emotion shown in a face to one of two other faces (emotion perception
      task). The degree to which the VLPFC regulated amygdala response during these
      tasks was assessed using a psychophysiological interaction (PPI) analysis.
      Compared with healthy subjects, manic patients had a significantly reduced VLPFC
      regulation of amygdala response during the emotion labeling task. These findings,
      taken in context with previous fMRI studies of bipolar mania, suggest that
      reductions in inhibitory frontal activity in these patients may lead to an
      increased reactivity of the amygdala.

PMID- 18063351
TI  - A decision support system to facilitate management of patients with acute
      gastrointestinal bleeding.
AB  - OBJECTIVE: To develop a model to predict the bleeding source and identify the
      cohort amongst patients with acute gastrointestinal bleeding (GIB) who require
      urgent intervention, including endoscopy. Patients with acute GIB, an
      unpredictable event, are most commonly evaluated and managed by non
      gastroenterologists. Rapid and consistently reliable risk stratification of
      patients with acute GIB for urgent endoscopy may potentially improve outcomes
      amongst such patients by targeting scarce healthcare resources to those who need
      it the most. DESIGN AND METHODS: Using ICD-9 codes for acute GIB, 189 patients
      with acute GIB and all available data variables required to develop and test
      models were identified from a hospital medical records database. Data on 122
      patients was utilized for development of the model and on 67 patients utilized to
      perform comparative analysis of the models. Clinical data such as presenting
      signs and symptoms, demographic data, presence of co-morbidities, laboratory data
      and corresponding endoscopic diagnosis and outcomes were collected. Clinical data
      and endoscopic diagnosis collected for each patient was utilized to
      retrospectively ascertain optimal management for each patient. Clinical
      presentations and corresponding treatment was utilized as training examples.
      Eight mathematical models including artificial neural network (ANN), support
      vector machine (SVM), k-nearest neighbor, linear discriminant analysis (LDA),
      shrunken centroid (SC), random forest (RF), logistic regression, and boosting
      were trained and tested. The performance of these models was compared using
      standard statistical analysis and ROC curves. RESULTS: Overall the random forest
      model best predicted the source, need for resuscitation, and disposition with
      accuracies of approximately 80% or higher (accuracy for endoscopy was greater
      than 75%). The area under ROC curve for RF was greater than 0.85, indicating
      excellent performance by the random forest model. CONCLUSION: While most
      mathematical models are effective as a decision support system for evaluation and
      management of patients with acute GIB, in our testing, the RF model consistently
      demonstrated the best performance. Amongst patients presenting with acute GIB,
      mathematical models may facilitate the identification of the source of GIB, need
      for intervention and allow optimization of care and healthcare resource
      allocation; these however require further validation.

PMID- 18063352
TI  - Body iron stores in relation to the metabolic syndrome, glycemic control and
      complications in female patients with type 2 diabetes.
AB  - BACKGROUND AND AIM: Studies suggest that iron plays a significant role in the
      development of diabetes and its complications. This study evaluates the
      associations of iron metabolism parameters with the metabolic syndrome (MS),
      control and complications in female patients with type 2 diabetes mellitus
      (T2DM). METHODS AND RESULTS: Ferritin, soluble Transferrin Receptor (sTfR),
      sTfR/Log ferritin ratio (sTfR-F index), iron, full blood count and high
      sensitivity C-reactive protein (hs-CRP) were determined in 110 female patients
      with T2DM. Steady state beta cell function (%B), insulin sensitivity (%S) and
      insulin resistance were assessed with homeostasis model. Patients were divided
      into tertiles of ferritin and sTfR-F index and according to the presence or
      absence of the MS and diabetic complications. Patients within the lowest tertile
      of the sTfR-F index had significantly higher fasting insulin, percent B, low
      density lipoprotein cholesterol and Apolipoprotein B than those in the highest
      tertile. Ferritin showed significant correlations with insulin, percent B and
      inverse correlations with adiponectin and percent S. The sTfR-F index was
      significantly correlated with insulin, percent B and lipid parameters. Correcting
      for hs-CRP abolished the correlations with ferritin but not the sTfR-F index.
      Higher indices of body iron were significantly associated with diabetes
      complications but no associations were found with MS, glucose or glycemic
      control. Multiple regression analysis with confounding variables showed ferritin
      and the sTfR-F index were not independently associated with diabetes
      complications. CONCLUSIONS: Association of ferritin with metabolic derangements
      and complications in diabetes is partly dependent on association with
      inflammation. Iron status, estimated with the sTfR-F index, is associated with
      metabolic derangements and complications but the associations are dependent on
      other risk factors. Prospective studies that use the sTfR-F index as a marker of
      iron status are required to confirm the role of iron in the etiopathogenesis of
      T2DM and its complications.

PMID- 18063353
TI  - Molecular determinants of insulin resistance, cell apoptosis and lipid
      accumulation in non-alcoholic steatohepatitis.
AB  - BACKGROUNDS AND AIMS: Non-alcoholic-steatohepatitis (NASH) is closely related to
      insulin resistance, but it is unknown whether insulin resistance may be localized
      in hepatocytes. This study investigates insulin signalling in liver tissue from
      NASH, and the molecular mechanisms by which insulin-resistance could lead to
      liver damage (apoptosis). Moreover, to investigate the mechanisms of lipid
      overload we studied key enzymes in hepatocytes lipid metabolism. METHODS AND
      RESULTS: In liver specimens from 11 patients with NASH and 7 histological normal
      livers, we measured total and phosphorylated Akt (active form), Bax and Bcl-2 by
      Western-blot analysis. In addition, we studied AMP-activated protein Kinase and
      Carnitine-Palmitoyl-Transferase-1 gene expression, key regulators of non
      esterified fatty acid synthesis and oxidation, by reverse transcription
      polymerase chain reaction. In NASH, phosphorylated Akt was impaired (104.3+/-10.6
      vs 152.6+/-22.4 AU, p<0.002) and correlated with necroinflammatory score (r=
      0.62; p<0.05). Bax/Bcl-2 ratio was increased in NASH. Moreover, we observed a
      decrease of AMP-activated protein Kinase (10.74+/-6 vs 144.7+/-41.6 AU, p<0.0001)
      and Carnitine-Palmitoyl-Transferase-1 gene expression (38.7+/-14.6 vs 192.1+/
      26.2 AU, p<0.0001), and both were correlated with steatosis score (r=-0.56,
      p<0.05, r=-0.87, p<0.05 respectively). CONCLUSIONS: Akt, a key molecule of
      insulin signalling and cell apoptosis is impaired in NASH, suggesting an
      important role of hepatic insulin resistance in liver failure. Moreover,
      decreased non-esterified fatty acid oxidation may cause hepatic lipid overload.

PMID- 18063354
TI  - Circadian variability of blood pressure in obese children.
AB  - BACKGROUND AND AIMS: The aim of the present study was to evaluate the circadian
      rhythm of blood pressure pattern in obese children, and to investigate if the
      lack of normal diurnal rhythm of blood pressure is associated with cardiovascular
      risk factors. METHODS AND RESULTS: 73 obese children (body weight [mean+/-SD]:
      89.0+/-17.8 kg; age [mean+/-SD]: 14.2+/-2.3 years), 42 dippers and 31 non-dippers
      were investigated. Following ambulatory blood pressure monitoring (ABPM),
      physical fitness testing was performed on a treadmill. Physical working capacity
      at 130, -150, -170 beat/min (PWC-130, -150, -170), resting and peak oxygen
      consumption (VO(2)rest, VO(2)peak) were determined. Forty-two percent of obese
      children were non-dipper. PWC-130 (74.8+/-48.8 watts; 48.0+/-38.5 watts), PWC-150
      (132.9+/-52.1 watts; 104.2+/-49.3 watts), PWC-170 (185.9+/-49.5 watts; 154.9+/
      53.4 watts) and VO(2)rest, ([mean+/-SD]: 0.29+/-0.08 L/min; 0.26+/-0.07 L/min),
      and VO(2) peak (2.77+/-0.61 L/min; 2.44+/-0.62 L/min) were significantly lower in
      the non-dipper group, as compared to dippers (p<0.05). The prevalence of
      hypertension, on the basis of ABPM, was significantly higher in the non-dipper
      group (45.2% vs 83.9%, p<0.001). This is due to increased prevalence of masked
      hypertension in the non-dipper group (19.0% vs 32.3%, p<0.001). CONCLUSION: The
      normal circadian variation of the blood pressure is frequently absent in obese
      children. Most of the non-dipper obese children are hypertensive, and their
      physical fitness is decreased.

PMID- 18063355
TI  - Physiological responses to high intensity, constant-load arm exercise in COPD.
AB  - The aim of the study was to compare the metabolic, ventilatory and dyspnoea
      responses of a single bout of high intensity, constant-load arm exercise to peak
      arm exercise in people with chronic obstructive pulmonary disease (COPD). Thirty
      people with COPD (mean age+/-SD=65+/-8 years; FEV1% predicted=56+/-12%) were
      included. All subjects performed an incremental arm exercise test to peak work
      capacity on an arm ergometer and, on a separate day, a constant-load arm exercise
      test at 80% of the peak work rate achieved on the incremental test. Throughout
      both exercise tests, oxygen consumption (VO2), minute ventilation (VE), dyspnoea
      and rate of perceived exertion (RPE) were measured each minute. Peak work rate on
      the incremental test was 33.0+/-10.1 W with a mean duration of 6.6+/-2.0 min. The
      mean duration of the constant-load test of 7.1+/-2.9 min was not significantly
      different to the incremental test (p=0.3). At end exercise, VE, dyspnoea and RPE
      for the constant-load test was significantly higher compared to the incremental
      test (VE: 41.3+/-14.4 L/min and 38.3+/-11.8 L/min; dyspnoea: 5.6+/-2.7 and 4.6+/
      2.1; RPE: 7.1+/-2.3 and 6.0+/-2.0; all p<0.05). Constant-load arm exercise at 80%
      peak work rate elicits higher ventilatory, dyspnoea and RPE responses at end
      exercise compared to incremental arm exercise in people with COPD. This finding
      suggests that an intensity of 80% peak work rate may be too high as an initial
      training intensity for supported arm exercise in people with COPD.

PMID- 18063356
TI  - Recent advances in cholesterol biosensor.
AB  - Biosensors have recently gained much attention in the field of health care for
      the management of various important analytes in a biological system. The area
      achieved tremendous progress from the time when the first Clark electrode for
      measurement of glucose was realized. Advances in the biosensor design are
      appearing at a high rate as these devices play increasingly important roles in
      our daily lives. The increasing incidences of cardiovascular diseases and cardiac
      arrest are major cause of death of humans world over. One of the most important
      reasons is hypercholesterolemia, i.e. increased concentration of cholesterol in
      blood. Hence estimation of cholesterol level in blood is important in clinical
      applications. This review aims to highlight the recent advances in materials and
      techniques for cholesterol biosensor design and construction.

PMID- 18063358
TI  - Human monoclonal antibodies by immortalization of memory B cells.
AB  - The administration of hyper immune sera to prevent or treat life-threatening
      infections is a remarkable milestone in medicine and biotechnology that has been
      achieved more than a century ago. Yet, the therapeutic use of monoclonal
      antibodies in this field has developed slowly over the last decades. Here we
      compare and contrast current methods to generate human monoclonal antibodies and
      highlight the advantages of exploiting the human antibody repertoire using a
      novel method that allows efficient immortalization and cloning of human memory B
      cells. This method, which has been successfully applied to isolate broadly
      neutralizing antibodies against SARS and H5N1 influenza viruses, is expected to
      accelerate the development of therapeutics in the field of infectious diseases
      not only by providing neutralizing antibodies for passive serotherapy, but also
      by generating relevant information for vaccine design.

PMID- 18063359
TI  - The multifaceted value of antidepressants in cancer therapeutics.

PMID- 18063357
TI  - Replicating and non-replicating viral vectors for vaccine development.
AB  - Viral vectors provide a convenient means to deliver vaccine antigens to select
      target cells or tissues. A broad spectrum of replicating and non-replicating
      vectors is available. An appropriate choice for select applications will depend
      on the biology of the infectious agent targeted, as well as factors such as
      whether the vaccine is intended to prevent infection or boost immunity in already
      infected individuals, prior exposure of the target population to the vector,
      safety, and the number and size of gene inserts needed. Here several viral
      vectors under development as HIV/AIDS vaccines are reviewed. A vaccine strategy
      based on initial priming with a replicating vector to enlist the innate immune
      system, target mucosal inductive sites, and prime both cellular and humoral
      systemic and mucosal immune responses is proposed. Subsequently, boosting with a
      replicating or non-replicating vector and/or protein subunits could lead to
      induction of necessary levels of protective immunity.

PMID- 18063360
TI  - Inherited multitumoral syndromes including colorectal carcinoma.
AB  - Inherited multitumoral syndromes including colorectal carcinoma are the
      followings: familial adenomatous polyposis (FAP), hereditary non-polyposis colon
      cancer (HNPCC) and Peutz-Jeghers syndrome (PJS). The studies of genotype
      phenotype correlation have shown that various types of colonic polyposis are
      related with germline mutation of adenomatous polyposis coli (APC) gene, that is
      also responsible for a wide number of extracolonic manifestations. Concerning
      severity of polyposis, it has been suggested to perform ileorectal anastomosis in
      patients with intermediate FAP, whereas it has been suggested to remove the
      rectum from the beginning and to perform ileopouch anastomosis in patients with
      severe FAP (germline APC mutations between codons 1250 and 1464, i.e. mutation
      cluster region-MCR). Concerning extracolonic manifestations, original studies
      from our laboratory have shown that three peculiar, even if unusual extracolonic
      manifestations of FAP, were in the 5' portion of the gene, but almost always
      outside of MCR. In particular, in some patients or in some kindreds all these
      manifestations may be present together. It is suggested, from one hand, because
      of the wide variety of genotype-phenotype correlation word of caution before
      selecting surgical treatment simply on the basis of the germline mutations, on
      the other hand co-segregation of some extracolonic manifestations could
      facilitate intensive screening, early diagnosis and optimal time for treatment.

PMID- 18063361
TI  - Stapled hemorrhoidopexy: day surgery or one day surgery?
AB  - Hemorrhoidal disease is one of the most common anorectal disorders, from 10% to
      20% of all patients admitted at a clinical investigation need to undergo surgery,
      stapled haemorrhoidopexy is gaining wide acceptance as an interesting, safe and
      less painful technique, but hemorrhage is one of the most serious early
      complications and is a severe complication in day surgery. In our day surgery
      proctology, surgical procedures represent about 32%. Of these, 24% are for
      hemorrhoidal disease, we present our protocol and experience for early and safe
      discharge, 6h after stapled hemorrhoidopexy surgery.

PMID- 18063362
TI  - Utilizing peanut husk (Arachis hypogaea L.) in the manufacture of medium-density
      fiberboards.
AB  - The main objective of this study was to investigate the potential of peanut husk
      (Arachis hypogaea L.) as a fiber-peanut mixture to produce fiberboards for
      general purposes. For panel production, the addition of peanut husk at various
      percentages to the wood fiber was the only variable. Panels produced utilizing
      peanut husk were compared to panels produced using 100% wood fiber. The chemical
      properties of peanut husk; holocellulose and lignin content, alcohol-benzene, hot
      and cold water, and dilute alkali (1% NaOH) solubility, were also determined.
      Results indicated that panels could be produced utilizing up to 30% peanut husk
      without affecting the usability of the panels. It was not possible to meet the
      minimum IB strength standards when peanut husk was added to the mixture. Higher
      additions resulted in panels having lower elastic and rupture moduli than the
      minimum requirements according to TS-EN standards.

PMID- 18063363
TI  - Water solubilization of DDGS via derivatization with phosphite esters.
AB  - Ethanol production from corn starch in the corn dry milling process leaves
      Distillers' Dry Grains and Solubles (DDGS) as a major by-product from which
      additional ethanol may be economically obtained from its glucan content. A
      challenge in processing the cellulose content of this material lies in its
      extensive inter-cellulose chain hydrogen bonding, which inhibits access of
      enzymes capable of cleaving glycosidic bonds, a transformation required for
      providing fermentable sugars. The phosphitylation of cellulosic OH groups using a
      reactive bicyclic phosphite ester is utilized to disrupt cellulosic hydrogen
      bonds, thus providing access to cellulose chains for further processing. We
      describe a method of pretreating DDGS with commercially available
      trimethylolpropane phosphite [P(OCH2)3CEt] in the presence of a slight molar
      excess of water to afford greater than 90% DDGS solubility in the reaction
      mixture in methanol and in water. Preliminary results using a model compound [D
      (+)-permethylated cellobiose] indicate that glycosidic bonds are cleaved as a
      consequence of this pretreatment.

PMID- 18063364
TI  - Design and optimization of imidazole derivatives as potent CXCR3 antagonists.
AB  - A series of imidazole derivatives have been designed and optimized for CXCR3
      antagonism, pharmacokinetic properties, and reduced formation of glutathione
      conjugates. Our efforts led to the discovery of potent CXCR3 antagonists with
      good pharmacokinetic properties. These compounds are useful tools for in vivo
      studies of CXCR3 function.

PMID- 18063365
TI  - A flavonoid gossypin binds to cyclin-dependent kinase 2.
AB  - Flavonoids have low toxicity and mild activity. In order to find flavonoids
      showing cyclin-dependent kinase 2 (CDK2) binding effects, 347 flavonoid
      derivatives were docked into the crystal structure of the CDK2. The docking study
      showed that gossypin has a good conformational match with CDK2, which was
      confirmed by the binding affinity assay using NMR experiments.

PMID- 18063366
TI  - Antiproliferative effects of dibenzocyclooctadiene lignans isolated from
      Schisandra chinensis in human cancer cells.
AB  - Dibenzocyclooctadiene lignans isolated from Schisandra chinensis showed
      antiproliferative effects in various human cancer cells. The methoxy groups at C
      3, C-4, C-3', and C-4', the hydroxyl group at C-8', and the stereo-configuration
      of the biphenyl ring and the angeloyl group might have influence on these
      activities. Additional studies indicate that one of mechanism of action of an
      active compound schizantherin C in A549 human lung cancer cells was related to
      the inhibition of cell cycle progression in G0/G1 phase.

PMID- 18063367
TI  - Substituted oxazolidinones as novel NPC1L1 ligands for the inhibition of
      cholesterol absorption.
AB  - Cholesterol absorption inhibition (CAI) represents an important treatment option
      for hypercholesterolemia. Herein, we report the design and evaluation of a series
      of substituted oxazolidinones as ligands for the Niemann Pick C1 Like 1 (NPC1L1)
      protein, a key mediator of cholesterol transport. Novel analogs were initially
      evaluated in a brush border membrane NPC1L1 binding assay; subsequently,
      promising compounds were evaluated in vivo for acute inhibition of cholesterol
      absorption. These studies identified analogs with low micromolar NPC1L1 binding
      affinity and acute in vivo efficacy of >50% absorption inhibition at 3mg/kg.

PMID- 18063368
TI  - Complexation of single strand telomere and telomerase RNA template polyanions by
      deoxyribonucleic guanidine (DNG) polycations: plausible anticancer agents.
AB  - Cancerous cell immortality is due to relatively high concentrations of telomerase
      enzyme which maintains telomere sequence during cell division. Deoxyribonucleic
      guanidine (DNG) is a positively charged DNA analog in which guanidine replaces
      the phosphordiester linkage of DNA. Mixed sequences of DNG and DNA
      oligonucleotides are referred to as chimera. Complexation of DNG and chimeric
      polycations with the complementary negatively charged non-coding telomere single
      strand d(5'-TTAGGG-3')(n) and the 11-base telomeric RNA template (5'-CUAACCCUAAC
      3') in the active site of telomerase has been studied. Calculated by ensemble
      sampling simulations in GBMV solvent model, we found that binding of
      complementary DNG hexamer with telomere is favored over that of DNA-telomere by
      approximately 10(6)-fold and binding of chimera hexamer is favored by
      approximately 10(4)-fold. Binding of complementary DNG with telomeric RNA is
      favored by 43 kcal/mol over telomere substrate binding with telomeric RNA.

PMID- 18063369
TI  - Can mammographic findings help discriminate between atypical ductal hyperplasia
      and ductal carcinoma in situ after needle core biopsy?
AB  - In a screening population of women, the mammographic characteristics for 68 cases
      of atypical ductal hyperplasia (ADH) diagnosed by needle core biopsy (NCB) were
      reviewed to seek mammographic findings which differentiate between ductal
      carcinoma in situ (DCIS) and ADH. A blinded analysis by two radiologists was
      performed for 48 cases with microcalcification. The mammographic findings were
      correlated with the surgical histological results of benign non-atypical, ADH and
      carcinoma (DCIS or invasive) to identify features which were associated with a
      higher or lower odds ratio (OR) for malignancy. Underestimates for malignancy
      occurred in 14 of 29 cases with granular calcification form (OR 7.9, 95%
      confidence interval (CI) 1.5-41) and 6 of 8 cases with segmental/linear branching
      distribution (OR 9.0, 95%CI 1.6-52). No malignancy was found at surgical excision
      in 16 cases with fine, rounded calcification. In conclusion, detailed assessment
      of calcification distribution and form gave helpful predictors for malignancy.
      Lesions with fine rounded calcification were always benign.

PMID- 18063370
TI  - Glyconanobiotics: Novel carbohydrated nanoparticle antibiotics for MRSA and
      Bacillus anthracis.
AB  - This report describes the synthesis and evaluation of glycosylated polyacrylate
      nanoparticles that have covalently-bound antibiotics within their framework. The
      requisite glycosylated drug monomers were prepared from one of three known
      antibiotics, an N-sec-butylthio beta-lactam, ciprofloxacin, and a penicillin, by
      acylation with 3-O-acryloyl-1,2-O-isopropylidene-5,6 bis((chlorosuccinyl)oxy)-d
      glucofuranose (7) or 6-O-acetyl-3-O-acryloyl-1,2-O-isopropylidene-5
      (chlorosuccinyl)oxy-alpha-d-glucofuranose (10). These acrylated monomers were
      subjected to emulsion polymerization in a 7:3 (w:w) mixture of butyl acrylate
      styrene in the presence of sodium dodecyl sulfate as surfactant (3 weight %) and
      potassium persulfate as a radical initiator (1 weight %). The resulting
      nanoparticle emulsions were characterized by dynamic light scattering and found
      to have similar diameters ( approximately 40 nm) and size distributions to those
      of our previously studied systems. Microbiological testing showed that the N-sec
      butylthio beta-lactam and ciprofloxacin nanoparticles both have powerful in vitro
      activities against methicillin-resistant Staphylococcus aureus and Bacillus
      anthracis, while the penicillin-bound nanoparticles have no antimicrobial
      activity. This indicates the need for matching a suitable antibiotic with the
      nanoparticle carrier. Overall, the study shows that even relatively large, polar
      acrylate monomers (MW>1000 amu) can be efficiently incorporated into the
      nanoparticle matrix by emulsion polymerization, providing opportunities for
      further advances in nanomedicine.

PMID- 18063371
TI  - Synthesis and structure-immunosuppressive activity relationships of bakuchiol and
      its derivatives.
AB  - A series of derivatives of bakuchiol were synthesized and tested in vitro for
      their cytotoxicity, and inhibition of T cell proliferation and B cell
      proliferation. The data obtained provided preliminary structure-activity
      relationships of the compounds as immunosuppressive activity.

PMID- 18063372
TI  - Novel AMPA and kainate receptor antagonists containing the pyrazolo[1,5
      c]quinazoline ring system: Synthesis and structure-activity relationships.
AB  - This paper reports the synthesis and AMPA, Gly/NMDA, and KA receptor binding
      affinities of a new set of 1,9-disubstituted-8-chloro-pyrazolo[1,5-c]quinazoline
      2-carboxylates 2-34. Binding data show that, in general, compounds 2-34 bind to
      the AMPA receptor with good affinity and selectivity. In particular, the obtained
      results indicate that the contemporary presence of a 1,2-dicarboxylic acid moiety
      and suitable benzo-substituents on the PQZ system is important to gain selective
      AMPA receptor antagonists. Moreover, this study shows that the presence of a 2
      carboxybenzoylamino substituent at position-9 (compounds 33-34) is important for
      obtaining selective KA receptor antagonists. Some selected compounds were also
      tested for their functional antagonistic activity at both AMPA and NMDA receptor
      ion channels.

PMID- 18063373
TI  - Conception of myeloperoxidase inhibitors derived from flufenamic acid by
      computational docking and structure modification.
AB  - The development of myeloperoxidase (MPO) inhibitors has been conducted using
      flufenamic acid as a lead compound. Computational docking of the drug and its
      analogs in the MPO active site was first attempted. Several molecules were then
      synthesized and assessed using three procedures for the measurement of their
      inhibiting activity: (i) the taurine assay, (ii) the accumulation of compound II,
      and (iii) the LDL oxidation by ELISA. Most of the synthesized molecules had an
      activity in the same range as flufenamic acid but none of them were able to
      inhibit the MPO-dependent LDL oxidation. The experiments however gave some useful
      indications for a rational conception of MPO inhibitors.

PMID- 18063374
TI  - Selective COX-2 inhibitors. Part 2: synthesis and biological evaluation of 4
      benzylideneamino- and 4-phenyliminomethyl-benzenesulfonamides.
AB  - Two series of 4-benzylideneamino- and 4-phenyliminomethyl-benzenesulfonamide
      derivatives were designed and synthesized for the evaluation as selective
      cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood
      (HWB). Extensive structure-activity relationships (SAR) were studied within these
      series. Several compounds were found to be novel and selective COX-2 inhibitors.
      Among them, the most potent and selective was 4-(3-carboxy-4-hydroxy
      benzylideneamino)benzenesulfonamide (20, LA2135), (IC(50)'s for COX-1: 85.13
      microM; COX-2: 0.74 microM; SI: 114.5), being more active COX-2 selective than
      celecoxib.

PMID- 18063375
TI  - An investigation of radon exhalation rate and estimation of radiation doses in
      coal and fly ash samples.
AB  - Coal is a technologically important material used for power generation. Its
      cinder (fly ash) is used in the manufacturing of bricks, sheets, cement, land
      filling etc. Coal and its by-products often contain significant amounts of
      radionuclides, including uranium which is the ultimate source of the radioactive
      gas radon. Burning of coal and the subsequent atmospheric emission cause the
      redistribution of toxic radioactive trace elements in the environment. In the
      present study, radon exhalation rates in coal and fly ash samples from the
      thermal power plants at Kolaghat (W.B.) and Kasimpur (U.P.) have been measured
      using sealed Can technique having LR-115 type II detectors. The activity
      concentrations of 238U, 232Th, and 40K in the samples of Kolaghat power station
      are also measured. It is observed that the radon exhalation rate from fly ash
      samples from Kolaghat is higher than from coal samples and activity concentration
      of radionuclides in fly ash is enhanced after the combustion of coal. Fly ash
      samples from Kasimpur show no appreciable change in radon exhalation. Radiation
      doses from the fly ash samples have been estimated from radon exhalation rate and
      radionuclide concentrations.

PMID- 18063376
TI  - Disruption of striatal glutamatergic transmission induced by mutant huntingtin
      involves remodeling of both postsynaptic density and NMDA receptor signaling.
AB  - We study the striatal susceptibility to NMDA receptor (NMDAR)-mediated injury of
      two Huntington's disease (HD) transgenic mice: R6/1 and R6/1:BDNF(+/-). We found
      that R6/1:BDNF(+/-) mice--which express reduced levels of BDNF--were more
      resistant than R6/1 mice to intrastriatal injection of quinolinate. This
      increased resistance is related to a differential reduction in expression of
      NMDAR scaffolding proteins, MAGUKs (PSD-95, PSD-93, SAP-102 and SAP-97) but not
      to altered levels or synaptic location of NMDAR. A robust reorganization of
      postsynaptic density (PSD) was detected in HD transgenic mice, shown by a switch
      of PSD-93 by PSD-95 in PSD. Furthermore, NMDAR signaling pathways were affected
      by different BDNF levels in HD mice; we found a reduction of synaptic alpha
      CaMKII (but not of nNOS) in R6/1:BDNF(+/-) compared to R6/1 mice. The specific
      regulation of MAGUKs and alpha CaMKII in striatal neurons may reflect a
      protective mechanism against expression of mutant huntingtin exon-1.

PMID- 18063377
TI  - Distribution of urocanic acid isomers between aqueous solutions and n-octanol,
      liposomes or bovine serum albumin.
AB  - The distribution of urocanic acid (UCA) isomers between aqueous solutions and n
      octanol, egg yolk phosphatidylcholine (eggPC) liposomes or bovine serum albumin
      (BSA) has been evaluated. Regarding its partitioning between water and n-octanol,
      the behaviour of both isomers is very similar, and the amount incorporated to the
      organic solvent is mostly determined by the fraction of the compound that, in the
      aqueous phase, is present as uncharged species. This implies that the highest
      hydrophobicity occurs near the isoelectric point. cis- and trans-UCA are readily
      incorporated into eggPC unilamellar liposomes. A simple pseudophase treatment of
      ultrafiltration data renders a binding constant of 0.20+/-0.04mL/mg for the trans
      isomer at pH 7.4. The binding constant decreases, by a factor two, at pH 5.0,
      suggesting that the negatively charged species is more favourably bound to the
      liposomes than the neutral species, which is mostly present as zwitterions. The
      cis-isomer, at both pHs, is less incorporated to the bilayers. trans-UCA and cis
      UCA readily bind to BSA at pH 7.4, with binding constants of 3400M(-1) and 6900M(
      1), respectively. This result suggests that, as in the octanol/water
      partitioning, hydrophobic interactions predominate and the degree of binding is
      determined by the fraction present as uncharged species. A smaller binding
      constant at pH 5.0 indicates that the charge of the protein is also plying a
      relevant role.

PMID- 18063378
TI  - Neoadjuvant treatment for pancreatic cancer--a review.
AB  - Pancreatic cancer is associated with a poor prognosis. While surgical resection
      is the only treatment that holds the potential of cure, a minority of patients
      are surgical candidates. Despite surgery, the overall survival rates remain low.
      Neoadjuvant treatment has been investigated both in the setting of resectable
      disease at diagnosis, or in an attempt to downstage locally advanced disease for
      resection. Single institution studies of neoadjuvant chemoradiation have
      demonstrated favourable outcomes, compared to similar series of patients treated
      with surgery with or without adjuvant therapy. For unresectable disease, partial
      or complete responses have been observed which have allowed some patients to
      subsequently undergo resection. The reports of neoadjuvant therapy for pancreatic
      cancer are heterogeneous with regards to patient population, treatment methods
      and modalities, making comparisons of different regimens inherently flawed. To
      date, no randomized controlled trials of neoadjuvant therapy have been conducted,
      however given the positive outcomes of single institutional series of neoadjuvant
      therapy this approach is worthy of further study.

PMID- 18063380
TI  - Response to "the effect of aspartame on the acetylcholinesterase activity in
      hippocampal homogenates of suckling rats" by Simintzi et al.

PMID- 18063379
TI  - Cytokine regulation of mucin secretion in a human middle ear epithelial model.
AB  - OBJECTIVES: Middle ear mucins are associated with otitis media (OM), contribute
      to hearing loss and are regulated by cytokines. This work investigates the
      regulation of mucin secretion from human middle ear epithelial cells (HMEEC) by
      inflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha
      (TNF-alpha) and cytokine inhibitors interleukin-1 receptor antagonist (IL-1ra)
      and anti-tumor necrosis factor-alpha antibody (TNFab). METHODS: HMEEC were
      exposed to IL-1beta and TNF-alpha in a dose- and time-dependent manner. Cytokine
      stimulated HMEEC were also exposed to IL-1ra and TNFab in a dose-dependent
      manner. Mucin secretion was characterized by exclusion chromatography and liquid
      scintillation. RESULTS: HMEEC exposed to IL-1beta and TNF-alpha demonstrated
      significant upregulation of mucin secretion in a dose-dependent fashion. Cultures
      exposed to IL-1beta at 100ng/ml and TNF-alpha at 200ng/ml showed increased mucin
      secretion in time-dependent experiments at 16h (P=0.00008) for TNF-alpha and 8
      (P=0.028) and 16h (P=0.00001) for IL-1beta. IL-1ra and TNFab inhibited the
      effects of increased mucin secretion by IL-1beta and TNF-alpha. CONCLUSIONS: IL
      1beta and TNF-alpha upregulate mucin secretion from HMEEC in a dose- and time
      dependant manner and these effects can be inhibited by cytokine blockade.
      Improved understanding of these mechanisms has the potential to alter the
      approach and management of OM and lead to novel therapeutic interventions.

PMID- 18063381
TI  - Putative palytoxin and its new analogue, ovatoxin-a, in Ostreopsis ovata
      collected along the Ligurian coasts during the 2006 toxic outbreak.
AB  - In this article we report on the liquid chromatography tandem mass spectrometry
      (LC-MS) investigation of plankton samples collected in the summer of 2006 along
      the Ligurian coasts, coinciding with a massive bloom of the tropical microalga
      Ostreopsis ovata. LC-MS analyses indicated the occurrence of putative palytoxin
      along with a much more abundant palytoxin-like compound never reported so far,
      which we named ovatoxin-a. On the basis of molecular formula, fragmentation
      pattern, and chromatographic behavior, the structure of ovatoxin-a appeared to be
      strictly related to that of palytoxin. We report also on the analysis of cultured
      O. ovata, which was necessary to unequivocally demonstrate that putative
      palytoxin and ovatoxin-a contained in field samples were actually produced by O.
      ovata itself.

PMID- 18063382
TI  - Gaseous iron(II) and iron(III) complexes with BINOLate ligands.
AB  - Electrospray ionization (ESI) of dilute solutions of 1,1'-bi-2-naphthol (BINOL)
      and iron(II) or iron(III) sulfate in methanol/water allows the generation of
      monocationic complexes of iron and deprotonated BINOL ligands with additional
      methanol molecules in the coordination sphere, and the types of complexes formed
      can be controlled by the valence of the iron precursors used in ESI. Thus,
      iron(II) sulfate leads to [(BINOLate)Fe(CH3OH)n]+ complexes (n=0-3), whereas
      usage of iron(III) sulfate allows the generation of [(BINOLdiate)-Fe(CH3OH)n]+
      cations (n=0-2); here, BINOLate and BINOLdiate stand for singly and doubly
      deprotonated BINOL, respectively. Upon collision-induced dissociation, the mass
      selected ions with n>0 first lose the methanol ligands and then undergo
      characteristic fragmentations. Bare [(BINOLdiate)Fe]+, a formal iron(III)
      species, undergoes decarbonylation, which is known as a typical fragmentation of
      ionized phenols and phenolates either as free species or as the corresponding
      metal complexes. The bare [(BINOLate)Fe]+ cation, on the other hand,
      preferentially loses neutral FeOH to afford an organic C20H12O+* cation radical,
      which most likely corresponds to ionized 1,1'-dinaphthofurane.

PMID- 18063384
TI  - Isomeric recognition by ion/molecule reactions: the ionized phenol
      cyclohexadienone case.
AB  - The isomerization process between ionized phenol and ionized cyclohexadienone is
      studied by performing ion/molecule reactions with several alkyl nitrites in a
      hexapole collision cell inserted in a six-sector mass spectrometer. The
      distinction between both isomeric species is readily achieved on the basis of the
      completely different reactivity patterns observed for them in subsequent
      reactions. When reacting with alkyl nitrite, ionized phenol undergoes two
      competitive reactions corresponding to the formal radical substitution of the
      hydroxylic hydrogen atom by respectively (i) the nitrosyl radical (m/z 123) and
      (ii) an alkoxyl radical (m/z 138 if alkyl=ethyl). Both reactions were
      theoretically demonstrated by density functional theory calculations [B3LYP/6
      311++G(d,p)+ZPE] to involve hydrogen-bridged radical cations as key
      intermediates. The ion/molecule reaction products detected starting from ionized
      cyclohexadienone as the mass-selected ions arise from *OAlkyl, *OH, and NO2*
      radical additions. The occurrence of a spontaneous ring-opening of
      cyclohexadienone radical ion into a distonic species is suggested to account for
      the observed ion/molecule reaction products. We also demonstrated that ionized
      cyclohexadienone is partly isomerized during a proton-transfer catalysis process
      into ionized phenol inside the Hcell with ethyl nitrite as the base. The
      molecular ions of phenol generated in such conditions consecutively undergo
      reactions producing m/z 123 and 138 radical cations. The proposed mechanism is
      supported by results of quantum chemical calculations.

PMID- 18063383
TI  - Gas phase reaction of substituted isoquinolines to carboxylic acids in ion trap
      and triple quadrupole mass spectrometers after electrospray ionization and
      collision-induced dissociation.
AB  - Within the mass spectrometric study of bisubstituted isoquinolines that possess
      great potential as prolylhydroxylase inhibitor drug candidates (e.g., FG-2216),
      unusually favored gas-phase formations of carboxylic acids after collisional
      activation were observed. The protonated molecule of [(1-chloro-4-hydroxy
      isoquinoline-3-carbonyl)-amino]-acetic acid was dissociated, yielding the 1
      chloro-4-hydroxy-isoquinoline-3-carboxylic acid methyleneamide cation. Subsequent
      dissociation caused the nominal elimination of 11 u that resulted from the loss
      of HCN and concomitant addition of oxygen to the product ion, which formed the
      protonated 1-chloro-4-hydroxy-isoquinoline-3-carboxylic acid. The preference of
      this structure under mass spectrometric conditions was substantiated by tandem
      mass spectrometry analyses using the corresponding methyl ester (1-chloro-4
      hydroxy-isoquinoline-3-carboxylic acid methyl ester) that eliminated methylene (
      14 u) upon collisional activation. Moreover, the major product ion of 1-chloro-4
      hydroxy-isoquinoline-3-carboxylic acid, which resulted from the loss of water in
      MS3 experiments, restored the precursor ion structure by re-addition of H2O.
      Evidences for these phenomena were obtained by chemical synthesis of proposed gas
      phase intermediates, H/D exchange experiments, high-resolution/high accuracy mass
      spectrometry at MSn level, and "ping-pong" analyses (MS7, in which the precursor
      ion was dissociated and the respective product ion isolated to regenerate the
      precursor ion for repeated dissociation. Based on these results, dissociation
      pathways for [(1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino]-acetic acid
      were suggested that can be further utilized for the characterization of
      structurally related compounds or metabolic products in clinical, forensic, or
      doping control analysis.

PMID- 18063386
TI  - Influence of ankle functional instability on the ankle electromyography during
      landing after volleyball blocking.
AB  - The purpose of this study was to describe, interpret and compare the EMG
      activation patterns of ankle muscles - tibialis anterior (TA), peroneus longus
      (PL) and gastrocnemius lateralis (GL) - in volleyball players with and without
      ankle functional instability (FI) during landing after the blocking movement.
      Twenty-one players with FI (IG) and 19 controls (CG) were studied. The cycle of
      movement analyzed was the time period between 200 ms before and 200 ms after the
      time of impact determined by ground reaction forces. The variables were analyzed
      for two different phases: pre-landing (200 ms before impact) and post-landing
      (200 ms after impact). The RMS values and the timing of onset activity were
      calculated for the three studied muscles, in both periods and for both groups.
      The co-activation index for TA and PL, TA and GL were also calculated.
      Individuals with FI presented a lower RMS value pre-landing for PL (CG=43.0+/
      22.0; IG=26.2+/-8.4, p<0.05) and higher RMS value post-landing (CG=47.5+/-13.3;
      IG=55.8+/-21.6, p<0.10). Besides that, in control group PL and GL activated first
      and simultaneously, and TA presented a later activation, while in subjects with
      FI all the three muscles activated simultaneously. There were no significant
      differences between groups for co-activation index. Thus, the rate of contraction
      between agonist and antagonist muscles is similar for subjects with and without
      FI but the activation individually was different. Volleyball players with
      functional instability of the ankle showed altered patterns of the muscles that
      play an important role in the stabilization of the foot-ankle complex during the
      performance of the blocking movement, to the detriment of the ligament complex,
      and this fact could explain the usual complaints in these subjects.

PMID- 18063385
TI  - Collisionally activated dissociation and electron capture dissociation provide
      complementary structural information for branched permethylated oligosaccharides.
AB  - Doubly charged sodiated and permethylated linear malto-oligosaccharides ({Glc}6
      {Glc}9), branched N-linked glycans (high-mannose type GlcNAc2Man5-9, and complex
      asialo- and disialylated-biantennary glycans) were analyzed by tandem mass
      spectrometry using collisionally-activated dissociation (CAD) and "hot" electron
      capture dissociation (ECD) available in a custom-built ESI FTICR mass
      spectrometer. For linear permethylated malto-oligosaccharides, both CAD and "hot"
      ECD produced glycosidic cleavages (B, Y, C, and Z ions), cross-ring cleavages (A-
      and X-type), and internal cleavages (B/Y and C/Y type) to provide sequence and
      linkage information. For the branched N-linked glycans, CAD and "hot" ECD
      provided complementary structural information. CAD generated abundant B and Y
      fragment ions by glycosidic cleavages, whereas "hot" ECD produced dominant C and
      Z ions. A-type cross-ring cleavages were present in CAD spectra. Complementary A-
      and X-type cross-ring fragmentation pairs were generated by "hot" ECD, and these
      delineated the branching patterns and linkage positions. For example, 0, 4An and
      3, 5An ions defined the linkage position of the major branch as the 6-position of
      the central core mannose residue. The internal fragments observed in CAD were
      more numerous and abundant than in "hot" ECD spectra. Since the triply charged
      (sodiated) molecular ion of the permethylated disialylated-biantennary N-linked
      glycan has relatively high abundance, it was isolated and fragmented in a "hot"
      ECD experiment and extensive fragment ions (glycosidic and complementary pairs of
      cross-ring cleavages) were generated to fully confirm the sequence, branching,
      and linkage assignments for this glycan.

PMID- 18063387
TI  - Characteristics of the nociceptive withdrawal response elicited under aware and
      unaware conditions.
AB  - BACKGROUND: Nociceptive withdrawal reflexes (NWR) are subject to supraspinal
      modulation. Therefore, awareness about a noxious stimulation may affect its
      characteristics. The goal of this study was to investigate the effect of
      different degrees of awareness on the NWR. METHOD: Eight subjects performed back
      and forth hand movements from a common starting point towards four visual targets
      during which NWR was evoked when subjects were either unaware or aware of a
      noxious stimulation (unaware-NWR and aware-NWR). For the comparison between the
      NWR under both conditions, onset latencies and kinematic variables were computed
      respectively from the recorded Biceps Brachii EMG and from the spatial
      coordinates of hand reflective markers. RESULTS: The onset latency of unaware-NWR
      (mean+/-SD 73.9+/-13 ms) was significantly shorter than that of the aware-NWR
      (91.1+/-27 ms, p<0.05). The total duration of the muscular activation was shorter
      in unaware-NWR than in aware-NWR. The slopes of the tangential velocity-time
      curves were steeper for unaware-NWR than for aware-NWR (p=0.057). CONCLUSIONS:
      The results suggest that supraspinal regulation of NWR under different degrees of
      awareness involves the re-parameterization of selected spatiotemporal aspects of
      a pre-structured motor response.

PMID- 18063389
TI  - Let's face it: it's a cortical network.
AB  - Face perception elicits activation within a distributed cortical network in the
      human brain. The network includes visual ("core") regions, which process
      invariant facial features, as well as limbic and prefrontal ("extended") regions
      that process changeable aspects of faces. Analysis of effective connectivity
      reveals that the major entry node in the "face network" is the lateral fusiform
      gyrus and that the functional coupling between the core and the extended systems
      is content-dependent. A model for face perception is proposed, in which the flow
      of information through the network is shaped by cognitive demands.

PMID- 18063388
TI  - Blood-flow magnetic resonance imaging of the retina.
AB  - This study describes a novel MRI application to image basal blood flow,
      physiologically induced blood-flow changes, and the effects of isoflurane
      concentration on blood flow in the retina. Continuous arterial-spin-labeling
      technique with a separate neck coil for spin labeling was used to image blood
      flow of the rat retina at 90 x 90 x 1500-microm resolution. The average blood
      flow of the whole retina was 6.3+/-1.0 ml/g/min under 1% isoflurane, consistent
      with the high blood flow in the retina reported using other techniques. Blood
      flow is relatively constant along the length of the retina, except it dipped
      slightly around the optic nerve head and dropped significantly at the distal
      edges where the retina terminates. Hyperoxia (100% O(2)) decreased blood flow
      25+/-6% relative to baseline (air) due to vasoconstriction. Hypercapnia (5%
      CO(2)+21% O(2)) increased blood flow 16+/-6% due to vasodilation. Increasing
      isoflurane (a potent vasodilator) concentration to 1.5% increased blood flow to
      9.3+/-2.7 ml/g/min. Blood-flow signals were confirmed to be genuine by repeating
      measurements after the animals were sacrificed in the MRI scanner. This study
      demonstrates a proof of concept that quantitative blood flow of the retina can be
      measured using MRI without depth limitation. Blood-flow MRI has the potential to
      provide unique insights into retinal physiology, serve as an early biomarker for
      some retinal diseases, and could complement optically based imaging techniques.

PMID- 18063390
TI  - Striatal dopamine transmission in healthy humans during a passive monetary reward
      task.
AB  - Research on dopamine (DA) transmission has emphasized the importance of increased
      phasic DA cell firing in the presence of unpredictable rewards. Using
      [(11)C]raclopride PET, we previously reported that DA transmission was both
      suppressed and enhanced in different regions of the striatum during an
      unpredictable reward task [Zald, D.H., Boileau, I., El Dearedy, W., Gunn, R.,
      McGlone, F., Dichter, G.S. et al. (2004). Dopamine transmission in the human
      striatum during monetary reward tasks. J. Neurosci. 24, 4105-4112]. However, it
      was unclear if reductions in DA release during this task reflected a response to
      the high proportion of nonrewarding trials, and whether the behavioral demands of
      the task influenced the observed response. To test these issues, we presented 10
      healthy subjects with an automated (passive) roulette wheel game in which the
      amount of reward and its timing were unpredictable and the rewarding trials
      greatly outnumbered the nonrewarding ones. As in the previous study, DA
      transmission in the putamen was significantly suppressed relative to a
      predictable control condition. A similar suppression occurred when subjects were
      presented with temporally unpredictable novel pictures and sounds. At present,
      models of DA functioning during reward do not account for this suppression, but
      given that it has been observed in two different studies using different reward
      paradigms, this phenomenon warrants attention. Neither the unpredictable reward
      nor the novelty conditions produced consistent increases in striatal DA
      transmission. These data suggest that active behavioral engagement may be
      necessary to observe robust statewise increases in DA release in the striatum.

PMID- 18063393
TI  - Compression therapy for occupational leg symptoms and chronic venous disorders -
      a meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: Leg discomfort and oedema are commonly attributed to a venous disorder
      (CVD) or chronic venous insufficiency (CVI) and treated with compression hosiery.
      The pressure needed to achieve clinical benefit is a matter of debate. DESIGN: We
      performed a meta-analysis of randomised controlled trials (RCT) that compared
      stockings exerting an ankle pressure of 10-20mmHg with placebo or no treatment
      and with stockings exerting a pressure of more than 20mmHg. METHODS: RCT were
      retrieved and analysed with the tools of the Cochrane Collaboration. Each study
      was reviewed independently. Subjective dichotomous and continuous factors and
      objective findings were pooled for statistical treatment. RESULTS: Eleven RCT
      fulfilled the predefined criteria. They included 1453 randomised subjects, 794
      healthy people exposed to various forms of stress, 552 patients with a chronic
      venous disorder or chronic venous insufficiency and 141 patients after varicose
      vein surgery. Over all, compression with 10-20mmHg had a clear effect on oedema
      and symptoms as compared with <10mmHg pressure, placebo stockings, or no
      treatment (p<.0001). No study showed a difference between 10-20 and >20mmHg
      stockings. CONCLUSIONS: Despite important methodological heterogeneity and
      sometimes sub-standard reporting the meta-analysis suggests that leg compression
      with 10-15mmHg is an effective treatment for CVD. Less pressure is ineffective
      and higher pressure may be of no additional benefit.

PMID- 18063391
TI  - Intensity non-uniformity correction using N3 on 3-T scanners with multichannel
      phased array coils.
AB  - Measures of structural brain change based on longitudinal MR imaging are
      increasingly important but can be degraded by intensity non-uniformity. This non
      uniformity can be more pronounced at higher field strengths, or when using
      multichannel receiver coils. We assessed the ability of the non-parametric non
      uniform intensity normalization (N3) technique to correct non-uniformity in 72
      volumetric brain MR scans from the preparatory phase of the Alzheimer's Disease
      Neuroimaging Initiative (ADNI). Normal elderly subjects (n=18) were scanned on
      different 3-T scanners with a multichannel phased array receiver coil at
      baseline, using magnetization prepared rapid gradient echo (MP-RAGE) and spoiled
      gradient echo (SPGR) pulse sequences, and again 2 weeks later. When applying N3,
      we used five brain masks of varying accuracy and four spline smoothing distances
      (d=50, 100, 150 and 200 mm) to ascertain which combination of parameters
      optimally reduces the non-uniformity. We used the normalized white matter
      intensity variance (standard deviation/mean) to ascertain quantitatively the
      correction for a single scan; we used the variance of the normalized difference
      image to assess quantitatively the consistency of the correction over time from
      registered scan pairs. Our results showed statistically significant (p<0.01)
      improvement in uniformity for individual scans and reduction in the normalized
      difference image variance when using masks that identified distinct brain tissue
      classes, and when using smaller spline smoothing distances (e.g., 50-100 mm) for
      both MP-RAGE and SPGR pulse sequences. These optimized settings may assist future
      large-scale studies where 3-T scanners and phased array receiver coils are used,
      such as ADNI, so that intensity non-uniformity does not influence the power of MR
      imaging to detect disease progression and the factors that influence it.

PMID- 18063394
TI  - Perioperative myocardial injury after elective open abdominal aortic aneurysm
      repair predicts outcome.
AB  - OBJECTIVE: Myocardial injury, detected by rises in cardiac troponin I (TnI), is
      common and associated with decreased survival following open AAA surgery. We
      examined the relationship between perioperative myocardial injury and
      postoperative outcome. DESIGN: Observational Cohort Study. METHODS: Forty-three
      consecutive patients who underwent elective open AAA repair were screened for
      perioperative myocardial injury or infarction using serial TnI measurements
      (taken on days 1, 3, and 7), ECG and clinical assessment. The primary outcome was
      survival free of cardiac failure, or myocardial infarction (MI) at follow-up.
      RESULTS: Twenty (47%) of the 43 patients had a TnI elevation. Of these, 11 (26%)
      patients met the criteria for MI. At a mean (+/-SD) follow-up of 1.5+/-0.8 years,
      12 (28%) subjects had experienced at least one endpoint event. Survival free of
      cardiac failure or MI was 55% in patients who had TnI rises compared to 87% in
      those without (P=0.02). Logistic regression revealed that TnI elevation was an
      independent predictor of outcome with an odds ratio of 5.4 (95% CI 1.2-2.4,
      P=0.03). CONCLUSION: Perioperative myocardial injury after elective open AAA
      repair predicts outcome after surgery. Routine TnI measurement should be
      considered in all patients, especially in those with high cardiovascular risk.

PMID- 18063396
TI  - CreA-mediated repression in Aspergillus nidulans does not require transcriptional
      auto-regulation, regulated intracellular localisation or degradation of CreA.
AB  - The major regulatory protein in carbon repression in Aspergillus nidulans is
      CreA. Strains constitutively over-expressing creA show normal responses to carbon
      repression, indicating that auto-regulation of creA is not essential for CreA
      mediated regulation. In these strains, high levels of CreA are present whether
      cells are grown in repressing or derepressing conditions, indicating large-scale
      degradation of CreA does not play a key role. CreA is located in the nucleus and
      cytoplasm in cells when grown in either repressing or derepressing conditions,
      and absence of CreB, CreD or AcrB does not affect either the localisation or
      amount of CreA. Therefore, CreA must require some modification or interaction to
      act as a repressor. Deletion analysis indicates that a region of CreA thought to
      be important for repression in Trichoderma reesei and Sclerotina sclerotiorum
      CreA homologues is not critical for function in Aspergillus nidulans.

PMID- 18063395
TI  - Mating is rare within as well as between clades of the human pathogen Candida
      albicans.
AB  - Candida albicans is a diploid yeast that can undergo mating and a parasexual
      cycle, but is apparently unable to undergo meiosis. Characterization of the
      population structure of C. albicans has shown that reproduction is largely clonal
      and that mating, if it occurs, is rare or limited to genetically related
      isolates. Because molecular typing has delineated distinct clades in C. albicans,
      we have tested whether recombination was common within clades, but rare between
      clades. Two hundred and three C. albicans isolates have been subjected to
      multilocus sequence typing (MLST) and the haplotypes at heterozygous MLST
      genotypes characterized. The C. albicans isolates were distributed among nine
      clades, of which five corresponded to those previously identified by Ca3
      fingerprinting. In each of these clades with more than 10 isolates, polymorphic
      nucleotide positions located on between 3 and 4 of the six loci were in Hardy
      Weinberg disequilibrium. Moreover, each of these polymorphic sites contained
      excess heterozygotes. This was confirmed by an expanded analysis performed on a
      recently published MLST dataset for 1044 isolates. On average, 66% of polymorphic
      positions in the individual clades were in significant excess of heterozygotes
      over the five clades. These data indicate that mating within clades as well as
      self-fertilization are both limited and that C. albicans clades do not represent
      a collection of cryptic species. The study of haplotypes at heterozygous loci
      performed on our dataset indicates that loss of heterozygosity events due to
      mitotic recombination is moderately common in natural populations of C. albicans.
      The maintenance of substantial heterozygosity despite relatively frequent loss of
      heterozygosity could result from a selective advantage conferred by
      heterozygosity.

PMID- 18063397
TI  - Neurodevelopmental evolution of West syndrome: a 2-year prospective study.
AB  - OBJECTIVE: The aim of this study was to evaluate the epileptic and developmental
      evolution in infants with West syndrome. METHODS: A prospective study of 21
      infants was performed, with a follow-up at 2 years. Serial assessment included
      long-term EEG monitoring, visual and auditory evaluation and assessment of
      neurodevelopment. RESULTS: Neurosensory and developmental impairments at the
      spasm onset were transitory in seven cases, including four cryptogenic forms. In
      all other cases, there was a progressive worsening in neurosensory and
      developmental impairments. The epileptic evolution was generally better: in 11 of
      the 16 infants without seizures at outcome, spasms had already disappeared by 2
      months after disease onset. Statistic analysis of results showed a correlation
      between neurosensory impairment and development throughout the whole follow-up.
      In addition, visual function at T1 resulted significant predictor of
      developmental outcome. Among the epileptic features, disorganization of slow
      sleep was an unfavorable prognostic factor. CONCLUSION: Some forms of West
      syndrome are confirmed to have a benign evolution: among them there are not only
      cryptogenic cases but also symptomatic ones without significant
      neurodevelopmental impairment. Abnormalities of sleep organization, expression of
      the pervasive epileptic disorder, seem to play a role in determining a
      developmental deterioration. Neurosensory impairment since the onset of the
      disease could be a relevant cause of the developmental disorder.

PMID- 18063398
TI  - Lafora disease: spectroscopy study correlated with neuropsychological findings.
AB  - PURPOSE: To evaluate the metabolic changes both in grey and white matter in
      Lafora disease using proton magnetic resonance spectroscopy and to determine the
      possible correlation with the pattern of cognitive impairment. METHODS: Five
      patients with Lafora disease and six healthy controls were included in the study.
      Patients underwent at the same time-point neuropsychological testing and 1[H]MRS,
      using PRESS sequences (TE=136 and 25 ms) positioned in the frontal and posterior
      cingulate gyrus cortexes and in the adjacent frontal and parietal white matter.
      RESULTS: Neuropsychological testing showed in all patients a prevalent
      involvement of performance abilities--with partial sparing of verbal competences-
      and of executive functions, suggesting a major involvement of frontal areas.
      Analysis of 1[H]MRS showed a statistically significant reduction in NAA/mI and
      NAA/Cr in grey matter of patients compared to controls, more significant in
      frontal regions. In white matter, a significant reduction of NAA/mI ratio was
      observed both in the frontal and parietal regions, associated with a reduction of
      the NAA/Cr only in the frontal white matter. NAA/mI was found to be the most
      statistically significant altered parameter in all regions studied and the only
      significantly altered ratio in strong correlation with all sets of
      neuropsychological parameters. CONCLUSIONS: Our study confirmed the predominant
      metabolic damage in the frontal cortex, also demonstrating NAA/mI ratio to be the
      most sensitive parameter to detect metabolic brain changes in Lafora disease;
      moreover, it evidenced frontal white matter spectroscopic changes. Both
      spectroscopy values and clinical features of cognitive impairment showed a
      prevalent frontal impairment.

PMID- 18063399
TI  - Effect of the oral leukotriene B4 receptor antagonist LTB019 on inflammatory
      sputum markers in patients with chronic obstructive pulmonary disease.
AB  - This study aimed to evaluate the effect of a LTB4 receptor antagonist on
      inflammatory markers in induced sputum, in particular sputum neutrophilia, in ex
      smokers with moderate stable chronic obstructive pulmonary disease (COPD). The
      trial followed a double-blind, randomized, cross-over design including two
      treatment periods (4 weeks) separated by a 4-week washout period. Sputum
      inductions and lung function measurements were carried out at the beginning of
      each period, and after 2 and 4 weeks. Twenty-four patients were included (18/6
      m/f; mean (+/-S.D.) age 64+/-5 years; FEV 1 57+/-10% predicted); the per-protocol
      population comprised 17 patients. No significant differences occurred between
      LTB019 and placebo regarding the percentage of sputum neutrophils (treatment
      means, 68.0% vs. 69.3%), total cell count (in units of 10(6)/mL, log e of
      treatment means: 1.56 vs. 1.27), or the levels of MPO, IL-8, and TNF-alpha. There
      were also no differences in FEV 1, FVC, or the use of rescue medication. We
      therefore conclude that a 4-week treatment with LTB019 had no effect on sputum
      neutrophil numbers and related cytokine levels in these patients, despite the
      plasma concentrations achieved being similar to those shown to prevent the ex
      vivo LTB4-induced upregulation of CD11b/18 on neutrophils. The present data
      suggest that LTB4 antagonism by LTB019 is not a promising therapeutic approach
      for attenuating chronic airway neutrophilia, at least in patients with moderate
      COPD.

PMID- 18063401
TI  - Seroprevalence of hepatitis E virus in blood donors in Khuzestan Province,
      southwest Iran.
AB  - OBJECTIVE: To determine the seroprevalence of hepatitis E virus (HEV) infection
      among volunteer blood donors in Khuzestan Province, Iran. Khuzestan is a war
      stricken area in the southwest of Iran, which shares a land, river, and sea
      border with Iraq. This region has suffered the heaviest public health system
      damage of all the Iranian provinces during a 25-year period of war and conflict.
      METHODS: A cross-sectional study was carried out among 400 urban volunteer blood
      donors of the regional blood banks, from May to December 2005. Serum samples from
      healthy blood donors were tested for IgG anti-HEV antibody using a specific
      enzyme linked immunoassay (ELISA) kit. RESULTS: The prevalence of HEV infection
      was found to be 11.5% (46/400). All patients were negative for anti-HIV, anti
      HBV, and anti-HCV antibodies. The data indicate that 14.6% (38/260) of HEV
      positive subjects were male, compared to 5.7% (8/140) of females; this difference
      is statistically significant (risk ratio=2.6, p<0.008). CONCLUSIONS: These
      findings demonstrate the high prevalence rate of anti-HEV among blood donors,
      particularly males.

PMID- 18063400
TI  - Isolated abdominal fat tissue inflammation and necrosis in a cat.
AB  - This report describes a rare clinical case of a 4.5-month-old, female domestic
      shorthair, cat with isolated abdominal fat tissue inflammation and necrosis,
      resembling human omental panniculitis. Its possible relationship with
      pancreatitis or bile induced chemical peritonitis is also discussed. The overall
      clinical course was considered benign. Initial clinical signs were vomiting and
      anorexia, presumably due to inflammation, followed by mass development. It was
      speculated that, eventually, the kitten was vomiting because of mechanical
      pressure from the mass, and that this pressure subsided as the kitten grew. The
      mass was surgically resected and no relapse was evident during the next 4 years.

PMID- 18063402
TI  - Clinical and laboratory features of Crimean-Congo hemorrhagic fever: predictors
      of fatality.
AB  - OBJECTIVE: To determine the predictors of fatality among patients with Crimean
      Congo hemorrhagic fever (CCHF) based on epidemiological, clinical, and laboratory
      findings. METHODS: Among the patients with possible CCHF who were referred to
      Ankara Numune Education and Research Hospital (ANERH) from the surrounding
      hospitals between 2003 and 2006, those with IgM antibodies and/or reverse
      transcriptase-polymerase chain reaction (RT-PCR) results positive for CCHF virus
      in their blood, and who had received only supportive treatment, were included in
      the study. RESULTS: Sixty-nine patients with CCHF were admitted to ANERH from
      various cities of the northeastern part of the central region and southern parts
      of the Black Sea region of Turkey. Eleven (15.9%) patients died. Age, gender,
      days from the appearance of symptoms to admission, and initial complaints except
      bleeding were similar between fatal and non-fatal cases (p>0.05). Among the
      clinical findings, ecchymosis (p=0.007), hematemesis (p=0.030), melena (p<0.001),
      somnolence (p<0.001), and gingival bleeding (p=0.044) were more common among
      fatal cases. The mean platelet count was 47.569 x 10(9)/l in non-fatal cases and
      12.636 x 10(9)/l in fatal cases (p=0.003). Among the fatal cases, the mean
      prothrombin time (PT; 18.4s vs. 13.4s; p<0.001) and the mean activated partial
      thromboplastin time (aPTT; 69.4s vs. 42.7s; p=0.001) were longer, and the mean
      alanine aminotransferase (ALT; 1688 vs. 293; p<0.001), mean aspartate
      aminotransferase (AST; 3028 vs. 634; p<0.001), mean lactate dehydrogenase (LDH;
      4245 vs. 1141; p<0.001), mean creatine phosphokinase (CPK; 3016 vs. 851; p=0.004)
      levels and the mean international normalized ratio (INR; 1.38 vs. 1.1; p<0.001)
      were higher. In a Cox proportional hazards model, thrombocytopenia of < or = 20 x
      10(9)/l (hazard rate (HR) 9.67; 95% confidence interval (CI) 1.16-80.68;
      p=0.036), a prolonged aPTT > or = 60s (HR 11.62; 95% CI 2.40-56.27; p=0.002),
      existence of melena (HR 6.39; 95% CI 1.64-24.93; p=0.008), and somnolence (HR
      6.30; 95% CI 1.80-22.09; p=0.004) were independently associated with mortality.
      CONCLUSIONS: Thrombocytopenia of < or = 20 x 10(9)/l, a prolonged aPTT > or =
      60s, the existence of melena, and somnolence were independent predictors of
      fatality.

PMID- 18063403
TI  - Effects of four-week high-fructose diet on gene expression in skeletal muscle of
      healthy men.
AB  - AIMS: A high-fructose diet (HFrD) may play a role in the obesity and metabolic
      disorders epidemic. In rodents, HFrD leads to insulin resistance and ectopic
      lipid deposition. In healthy humans, a four-week HFrD alters lipid homoeostasis,
      but does not affect insulin sensitivity or intramyocellular lipids (IMCL). The
      aim of this study was to investigate whether fructose may induce early molecular
      changes in skeletal muscle prior to the development of whole-body insulin
      resistance. METHODS: Muscle biopsies were taken from five healthy men who had
      participated in a previous four-week HFrD study, during which insulin sensitivity
      (hyperinsulinaemic euglycaemic clamp), and intrahepatocellular lipids and IMCL
      were assessed before and after HFrD. The mRNA concentrations of 16 genes involved
      in lipid and carbohydrate metabolism were quantified before and after HFrD by
      real-time quantitative PCR. RESULTS: HFrD significantly (P<0.05) increased
      stearoyl-CoA desaturase-1 (SCD-1) (+50%). Glucose transporter-4 (GLUT-4)
      decreased by 27% and acetyl-CoA carboxylase-2 decreased by 48%. A trend toward
      decreased peroxisomal proliferator-activated receptor-gamma coactivator-1alpha
      (PGC-1alpha) was observed (-26%, P=0.06). All other genes showed no significant
      changes. CONCLUSION: HFrD led to alterations of SCD-1, GLUT-4 and PGC-1alpha,
      which may be early markers of insulin resistance.

PMID- 18063404
TI  - Frailty and Parkinson's disease: theories and clinical implications.

PMID- 18063405
TI  - How actions create--not just reveal--preferences.
AB  - The neo-classical economics view that behavior is driven by - and reflective of -
      hedonic utility is challenged by psychologists' demonstrations of cases in which
      actions do not merely reveal preferences but rather create them. In this view,
      preferences are frequently constructed in the moment and are susceptible to
      fleeting situational factors; problematically, individuals are insensitive to the
      impact of such factors on their behavior, misattributing utility caused by these
      irrelevant factors to stable underlying preferences. Consequently, subsequent
      behavior might reflect not hedonic utility but rather this erroneously imputed
      utility that lingers in memory. Here we review the roles of these streams of
      utility in shaping preferences, and discuss how neuroimaging offers unique
      possibilities for disentangling their independent contributions to behavior.

PMID- 18063406
TI  - Determination of aliphatic amines using fluorescence intensity of 4-methyl
      umbelliferone.
AB  - Effect of aliphatic amines and their concentration on fluorescence intensity of 4
      methyl umbelliferone (4-MU) one of coumarin derivative were investigated. This
      compound has blue light emission under UV lamp in methanolic solution. Spectral
      investigation of 4-MU solution containing amine compounds showed lower intensity
      at 350-410 nm (quenching region) and higher intensity at 430-500 nm (enhancing
      region) as compared to pure methanolic solution of 4-MU. Fluorescence intensity
      at isoemitting point was independent from concentration of amines. The variation
      of fluorescence intensity could be used for determination of aliphatic amines in
      both quenching and enhancing region. Linear ranges for determination of amines in
      the quenching region were obtained from Stern-Volmer diagram of 4-MU.
      Determination of amines at fluorescence enhancing region using inverse
      fluorescence intensity against inverse amine concentration (bireciprocal plot)
      were investigated and related equations was also proposed.

PMID- 18063407
TI  - Evaluation of the potential genotoxic effects of rTMS on the rat brain and
      current density mapping.
AB  - OBJECTIVE: The objectives of this work were: (i) to evaluate the relevance for
      clinical studies of repetitive transcranial magnetic stimulation (rTMS)
      investigations on rats, (ii) to investigate the occurrence of DNA damage in rat
      brain cells following rTMS under conditions similar to those used in clinical
      treatment of depression. METHODS: Rats were exposed to 2000 magnetic pulses at
      100% of motor threshold (MT). Software, written to take detailed anatomical and
      conductivity data into account, was used to map current density in the rat brain.
      A method was developed for standardizing magnetic pulse efficacy to facilitate
      comparison with other rTMS studies. Genotoxicity was explored using the alkaline
      comet assay on rat brain cells, measuring Olive moment and %DNA in the tail.
      RESULTS: The current density was ca. 6.6 A/m2 in the motor cortex at MT (Motor
      Cortex Threshold Densities: MCTDs), 5.2 A/m2 in the brain (range 0-17 A/m2), and
      2.0 A/m2 at prefrontal cortex. Similar standard MCTDs were found in rats and
      humans. Concerning the comet assay, both Olive moment and %DNA in the tail, there
      was no statistically-significant difference between rTMS-exposed and sham-exposed
      brain cell samples. In contrast, significant increases in both parameters were
      detected in positive controls. CONCLUSIONS: Under the assumptions developed in
      the discussion, these data showed no evidence that the standard current density
      at motor threshold in human motor cortex would differ from that in rats.
      Furthermore, there was no evidence of DNA damage in rat brain cells following a
      single scheme of rTMS, under conditions similar to the clinical treatment of
      depression. SIGNIFICANCE: This study supports the use of rats as a model for
      studying the bioeffects of rTMS (molecular targets, action mechanisms,
      toxicology, etc.) and suggests that a single rTMS scheme, similar to that used
      daily in the treatment of depression, is not genotoxic.

PMID- 18063408
TI  - High-frequency oscillations change in parallel with short-interval intracortical
      inhibition after theta burst magnetic stimulation.
AB  - OBJECTIVE: Theta burst transcranial magnetic stimulation (TBS) causes changes in
      motor cortical excitability. In the present study, somatosensory-evoked
      potentials (SEPs) and high-frequency oscillations (HFOs) were recorded before and
      after TBS over the motor cortex to examine how TBS influenced the somatosensory
      cortex. METHODS: SEPs following electric median nerve stimulation were recorded,
      and amplitudes for the P14, N20, P25, and N33 components were measured and
      analyzed. HFOs were separated by 400-800 Hz band-pass filtering, and root-mean
      square amplitudes were calculated from onset to offset. SEPs and HFOs were
      measured before and after application of either intermittent or continuous TBS
      (iTBS/cTBS; 600 total pulses at 80% active motor threshold) over the motor
      cortex. Motor-evoked potentials (MEPs) and short-interval intracortical
      inhibition (SICI) of the first dorsal interosseous muscle were examined before
      and after TBS. RESULTS: MEPs, SICI, and HFO amplitudes were increased and
      decreased significantly after iTBS and cTBS, respectively. Wide-band SEPs did not
      change significantly after TBS. CONCLUSIONS: TBS changed the cortical
      excitability of the sensorimotor cortices. Changes in HFOs after TBS were
      parallel to those in SICI. SIGNIFICANCE: The mechanisms of changes in HFOs after
      TBS may be the same as those in SICI.

PMID- 18063409
TI  - The clinical diagnostic utility of transcranial magnetic stimulation: report of
      an IFCN committee.
AB  - The review focuses on the clinical diagnostic utility of transcranial magnetic
      stimulation (TMS). The central motor conduction time (CMCT) is a sensitive method
      to detect myelopathy and abnormalities may be detected in the absence of
      radiological changes. CMCT may also detect upper motor neuron involvement in
      amyotrophic lateral sclerosis. The diagnostic sensitivity may be increased by
      using the triple stimulation technique (TST), by combining several parameters
      such as CMCT, motor threshold and silent period, or by studying multiple muscles.
      In peripheral facial nerve palsies, TMS may be used to localize the site of nerve
      dysfunction and clarify the etiology. TMS measures also have high sensitivity in
      detecting lesions in multiple sclerosis and abnormalities in CMCT or TST may
      correlate with motor impairment and disability. Cerebellar stimulation may detect
      lesions in the cerebellum or the cerebellar output pathway. TMS may detect upper
      motor neuron involvement in patients with atypical parkinsonism and equivocal
      signs. The ipsilateral silent period that measures transcallosal inhibition is a
      potential method to distinguish between different parkinsonian syndromes. Short
      latency afferent inhibition (SAI), which is related to central cholinergic
      transmission, is reduced in Alzheimer's disease. Changes in SAI following
      administration of cholinesterase inhibitor may be related to the long-term
      efficacy of this treatment. The results of MEP measurement in the first week
      after stroke correlate with functional outcome. We conclude that TMS measures
      have demonstrated diagnostic utility in myelopathy, amyotrophic lateral sclerosis
      and multiple sclerosis. TMS measures have potential clinical utility in
      cerebellar disease, dementia, facial nerve disorders, movement disorders, stroke,
      epilepsy, migraine and chronic pain.

PMID- 18063410
TI  - Efficient reduction of stimulus artefact in TMS-EEG by epithelial short
      circuiting by mini-punctures.
AB  - OBJECTIVE: We aimed at comparing the effects of two different electrode-to-skin
      contact preparation techniques on the stimulus artefact induced by transcranial
      magnetic stimulation (TMS) in electroencephalography (EEG) signals. METHODS: Six
      healthy subjects participated in a combined navigated brain stimulation (NBS) and
      EEG study. Electrode contacts were first prepared in the standard way of rubbing
      the skin using a wooden stick with a cotton tip. The location of hand motor area
      and the motor threshold (MT) was determined for each subject. Then, the TMS
      induced artefact was measured at 60%, 80%, 100% and 120% of the MT. Subsequently,
      the epithelium under the electrode contacts was electrically short-circuited by
      puncturing with custom-made needles and the stimulation sequences were
      replicated. The artefact was compared between the preparation techniques.
      RESULTS: The TMS-induced artefact was significantly reduced after puncturing. In
      addition, the size and duration of the artefact depended on the applied
      stimulation intensity. The reduction of the artefact was largest in electrodes at
      and close to the stimulation site. CONCLUSIONS: Mini-puncturing technique enables
      more accurate analysis of TMS-induced short-latency phenomena in EEG during NBS,
      and it may aid in the examination of the short distance neural connectivity
      beneath and close to the stimulation site. SIGNIFICANCE: This study describes a
      practical skin preparation method that significantly improves the utility of TMS
      EEG method in studying short-latency cortical connectivity.

PMID- 18063412
TI  - Host-pathogen interactions in sepsis.
AB  - Sepsis is a major health problem. The concept that sepsis mortality is the result
      of an uncontrolled hyperinflammatory host response has recently been challenged.
      It is now widely thought that the host response to sepsis involves many,
      concomitant, integrated, and often antagonistic processes that involve both
      exaggerated inflammation and immune suppression. Several novel mediators and
      pathways have been shown to play a part. Moreover, evidence is accumulating that
      microbial virulence and bacterial load contribute to the host response and the
      outcome of severe infections. A complex and dynamic interaction exists between
      pathogens and host immune-defence mechanisms during the course of invasive
      infection. Some pathogens have acquired the capacity to communicate with each
      other and sense the host's vulnerabilities. Bidirectional signals are detectable
      at the critical interface between the host and microbial invaders. The outcome of
      this interaction determines the fate of the host at the outset of the septic
      process. A formidable array of innate and acquired immune defences must be
      breached if a pathogen is to successfully disseminate and cause severe sepsis and
      septic shock. This Review summarises current knowledge of microbial pathogenesis
      and host-pathogen interactions during sepsis and the ensuing development of
      potential therapeutics.

PMID- 18063411
TI  - Fast voluntary neck movements in patients with cervical dystonia: a kinematic
      study before and after therapy with botulinum toxin type A.
AB  - OBJECTIVE: To study fast voluntary neck movements in patients with cervical
      dystonia (CD) before and after therapy with botulinum toxin type-A (BTX-A).
      METHODS: A selected sample of 15 patients with CD (with prevalent torticollis)
      and 13 age-matched control subjects performed both right and left rotational, and
      flexion and extension neck movements as fast as possible. Movements were recorded
      with a motion analysis system (SMART, BTS). Movement time, angular amplitude, and
      peak angular velocity were analyzed. In patients, rotational neck movements were
      pooled as "pro-dystonic" (toward the dystonic side) and "anti-dystonic" (toward
      the non-dystonic side). Results obtained in patients before BTX-A treatment were
      compared with those of control subjects. The effect of BTX-A treatment was
      evaluated by comparing movement performance before and after treatment. RESULTS:
      Before receiving BTX-A, patients performed pro- and anti-dystonic movements with
      lower peak angular velocity than control subjects. Pro-dystonic movements had a
      reduced angular amplitude. Anti-dystonic movements showed an abnormally long
      movement time. Flexion and extension movements required longer movement times,
      but the other kinematic variables were normal. After BTX-A injections, pro
      dystonic movement amplitude and anti-dystonic movement peak angular velocity
      increased, whereas flexion and extension movements remained unchanged.
      CONCLUSIONS: Before BTX-A injection patients with CD perform fast voluntary neck
      movements abnormally and BTX-A injections improved their peak velocity and
      amplitude. SIGNIFICANCE: Kinematic studies can detect specific neck movement
      disturbance in patients with CD, and can quantify both the severity of clinical
      picture and the effect of BTX-A injections in these patients.

PMID- 18063413
TI  - Clinical and electroencephalographic features in patients with CDKL5 mutations:
      two new Italian cases and review of the literature.
AB  - Clinical features and electroencephalographic findings of two patients affected
      by a previously unreported cyclin-dependent kinase-like 5 (CDKL5) gene mutation
      are described. Both patients had the Hanefeld variant phenotype with early-onset
      seizures, but different degrees of clinical severity. In fact, patient 1 was not
      drug-resistant and is responding to a single drug. On the contrary, patient 2,
      like most reported cases, has severe epilepsy, exhibits electroencephalographic
      changes, and is drug resistant. We suggest that the pseudoperiodic patterns
      observed on the EEGs for these cases represent this genetic form of epilepsy,
      though differing in frequency, voltage, and associated patterns. This is in
      agreement with data reported by other authors indicating that no unique pattern
      can be identified in subjects with CDKL5 mutations. Thus, a CDKL5 investigation
      should be performed in developmentally delayed patients with early-onset
      seizures, including drug-resistant subjects with severe EEG changes, as well as
      in patients with milder, drug-responsive forms of epilepsy.

PMID- 18063414
TI  - A noninvasive, presurgical expressive and receptive language investigation in a 9
      year-old epileptic boy using near-infrared spectroscopy.
AB  - The intracarotid amobarbital test (IAT) is used for presurgical evaluation of
      language lateralization. However, this procedure has many limitations, especially
      in children. As an alternative to IAT, in the case described here, near-infrared
      spectroscopy (NIRS) was used to investigate expressive and receptive language
      lateralization as part of the presurgical evaluation of a 9-year-old Yiddish
      speaking boy with a probable left temporal epileptic focus. This child could not
      tolerate IAT or functional MRI. He underwent two NIRS recording sessions while
      performing expressive and receptive language tasks. Results indicated
      predominantly left-sided expressive language in Broca's area with ipsilateral
      cortical recruitment of more posterior regions. Receptive language showed a
      bilateral cerebral pattern, perhaps as an expression of cerebral plasticity or
      compensation in this young patient. This case report illustrates that NIRS may
      contribute to presurgical investigation and could become a noninvasive
      alternative to IAT and functional MRI in determining speech lateralization in
      children.

PMID- 18063415
TI  - Perianal fistulizing Crohn's disease: a call to action.
AB  - The advent of biological therapies has focused attention on the importance of
      healing luminal Crohn's disease, thereby modifying the disease course. Perianal
      fistulas are common in Crohn's disease and often have a poor prognosis, with
      permanent sphincter and perineal tissue destruction. The importance of healing
      these fistulas has been less well appreciated. Management still often is left in
      surgical hands alone, rather than the optimal combination of surgery, infection
      control, and immunosuppression. Drug therapy often is haphazard, and the means of
      assessing healing over a long time period has been characterized poorly. Recent
      studies have suggested that many of these patients can achieve fistula healing,
      at least in the medium term. We therefore call for more active intervention, with
      the goal of healing, in these sick patients. Perianal fistulas lead to
      substantial physical and emotional distress because of pain, discharge,
      incontinence, perineal and genital disfigurement, and slow resolution even with
      treatment. The advent of accurate anal imaging, improved knowledge of surgical
      outcomes, and potent biological therapies make it timely to reflect on current
      best-management strategies.

PMID- 18063417
TI  - Confocal laser endomicroscopy for in vivo diagnosis of early squamous cell
      carcinoma in the esophagus.
AB  - BACKGROUND & AIMS: Confocal laser endomicroscopy has been shown to allow direct
      histologic imaging of gastrointestinal tumors in vivo. This study was designed to
      assess the potential of endomicroscopy for predicting histology in vivo during
      routine endoscopy in patients with early squamous cell cancer. METHODS: Twenty
      one consecutive patients with suspected early squamous cell cancer who had been
      referred for endoscopic therapy to a tertiary-care academic medical center were
      included in this prospective study. After staining with 0.5% Lugol's solution and
      injection of 500 mg fluorescein sodium, unstained mucosal areas were examined
      using confocal imaging. Images of each scanned lesion were acquired and stored
      digitally, and in vivo diagnosis was performed during ongoing endoscopy. Biopsy
      specimens were taken from every lesion. The confocal images were reviewed by 2
      endoscopists, who were blinded to the histology and endoscopic appearance.
      RESULTS: Confocal images were acquired from 43 lesions in 21 patients. Twenty
      seven of the 43 lesions (63%) were proven to be squamous cell cancer on
      histology. All squamous cell cancers were diagnosed correctly by endomicroscopy
      and 2 lesions were falsely diagnosed as neoplastic. The overall accuracy was 95%,
      and the sensitivity and specificity were 100% and 87%, respectively.
      Intraobserver agreement was almost perfect (kappa = 0.95) and interobserver
      agreement was substantial (kappa = 0.79). CONCLUSIONS: Confocal laser
      endomicroscopy is able to provide virtual histology of early squamous cell
      cancers with a high degree of accuracy and can facilitate rapid diagnosis during
      routine endoscopy.

PMID- 18063416
TI  - American founder mutation for attenuated familial adenomatous polyposis.
AB  - BACKGROUND & AIMS: Specific mutations in the adenomatous polyposis coli (APC)
      gene can lead to an attenuated form of familial adenomatous polyposis (AFAP).
      Although AFAP mutation carriers have a 69% risk of colorectal cancer by age 80,
      clinical recognition remains a challenge in some cases because they present with
      few colonic adenomas and are difficult to distinguish clinically from patients
      with sporadic polyps. METHODS: Family relationships were established using family
      history reports, the Utah Population Database, and the public records of the
      Mormon Church. Genetic analysis of representative family members was performed
      using a 10,000 single nucleotide polymorphism array platform. Colonoscopy data
      were available on 120 individuals with the AFAP mutation. RESULTS: Two large AFAP
      kindreds with the identical APC disease-causing mutation (c.426_427delAT) were
      linked to a founding couple who came to America from England around 1630. Genetic
      analysis showed that the 2 families share a conserved haplotype of 7.17 Mbp
      surrounding the mutant APC allele. The data show that 36.6% of the mutation
      positive family members have fewer than 10 colonic adenomatous polyps, and 3
      (6.8%) of these individuals were diagnosed with colorectal cancer. CONCLUSIONS:
      In view of the apparent age of this mutation, a notable fraction of both multiple
      adenoma patients and perhaps even colon cancer cases in the United States could
      be related to this founder mutation. The colon cancer risk associated with the
      mutation makes genetic testing of considerable importance in patients with a
      personal or family history of either colonic polyps or cancer at a young age.

PMID- 18063418
TI  - Staphylococcal enterotoxins G and I, a cause of severe but reversible neonatal
      enteropathy.
AB  - BACKGROUND & AIMS: Staphylococcus aureus is recognized to produce toxins A-E and
      toxic shock syndrome toxin-1 associated with food poisoning and toxic shock
      syndrome. Enterotoxins G and I co-exist in the same S aureus strains
      (staphylococcal enterotoxin G and staphylococcal enterotoxin I) and are
      implicated in scarlet fever and toxic shock. We report these enterotoxins as
      causative agents of 2 cases of neonatal intractable diarrhea with enteropathy.
      METHODS: We used a note review for this study. Stool culture, multiplex
      polymerase chain reaction for enterotoxin, duodenal biopsy specimens for H&E,
      periodic acid-Schiff staining, and electron microscopy were used. RESULTS: Infant
      1 had diarrhea from age 2 weeks and was referred at age 5 weeks with weight less
      than the 0.4th percentile. Infant 2 was referred at age 7 weeks with 4 weeks' of
      diarrhea, weight less than the 0.4th percentile. Both infants were severely
      malnourished. Elemental feeds were not tolerated and total parenteral nutrition
      was required. S aureus producing staphylococcal enterotoxin G and staphylococcal
      enterotoxin I was isolated in stools from both infants. Clinical improvement
      occurred after intravenous flucloxacillin and parenteral nutrition. Histology
      showed subtotal villous atrophy (H&E) with abnormal brush border (periodic acid
      Schiff). Electron microscopy showed severe microvilli destruction, dilated
      mitochondria, and lysosomes containing cellular debris. Repeat histology was
      normal in infant 2, age 3 months, off parenteral nutrition, showed return to
      normal. Currently, both infants are 2 years of age and are thriving on a normal
      diet. CONCLUSIONS: Staphylococcal enterotoxin G- and I-induced enteropathy is a
      life-threatening condition, causing reversible disruption of enterocyte
      ultrastructure that responds well to supportive treatment with flucloxacillin and
      parenteral nutrition This condition should be a differential diagnosis of
      neonatal early onset diarrhea.

PMID- 18063419
TI  - Racial and ethnic disparities in the prevalence of Barrett's esophagus among
      patients who undergo upper endoscopy.
AB  - BACKGROUND & AIMS: The incidence of esophageal adenocarcinoma (EAC) in blacks and
      Hispanics is well-described, but racial differences in the risk of Barrett's
      esophagus (BE) have not been directly studied. It is important to determine
      whether race and ethnicity can be identified as risk factors for the development
      of metaplasia, neoplastic progression, or both. METHODS: We performed a single
      center retrospective cross-sectional analysis of all patients who underwent upper
      endoscopy during a 1-year period. Patients with a prior endoscopy within 5 years
      or known BE or EAC were excluded. Suspected cases of BE were confirmed by
      pathology report. RESULTS: A total of 2100 patients met inclusion criteria.
      Whites (37.7%), blacks (11.8%), and Hispanics (22.2%) comprised the majority.
      Whites had a significantly higher prevalence of BE than Hispanics (6.1% vs 1.7%,
      P = .0002) and blacks (6.1% vs 1.6%, P = .004). In multivariable analysis,
      factors associated with decreased risk of BE were black race (odds ratio [OR],
      0.34; 95% confidence interval [CI], 0.12-0.97) and Hispanic ethnicity (OR, 0.38;
      95% CI, 0.18-0.84). Male sex (OR, 1.86; 95% CI, 1.20-2.87), reflux symptoms (OR,
      2.87; 95% CI, 1.84-4.45), hiatal hernia (OR, 3.53; 95% CI, 2.17-5.72), and older
      age were associated with increased risk of BE. CONCLUSIONS: Among patients who
      undergo upper endoscopy, blacks and Hispanics have a significantly lower
      prevalence of BE compared with whites. These differences in prevalence are
      comparable to the relative incidence rates observed with EAC, implying that
      progression from BE to adenocarcinoma does not vary by race/ethnicity. Reasons
      for lower rates of BE in Hispanics and blacks need further investigation.

PMID- 18063420
TI  - Double-balloon endoscope for failed conventional colonoscopy.

PMID- 18063421
TI  - Ribavirin posology, observance, and sustained virologic response.

PMID- 18063422
TI  - Trypsinogen copy number mutations in patients with idiopathic chronic
      pancreatitis.
AB  - BACKGROUND & AIMS: We have recently reported that the triplication of a
      approximately 605 kilobase segment containing the PRSS1 (encoding cationic
      trypsinogen) and PRSS2 (encoding anionic trypsinogen) genes causes hereditary
      pancreatitis. Here we went further to investigate whether this copy number
      mutation could account for some unidentified French white patients with
      idiopathic chronic pancreatitis (ICP) or familial chronic pancreatitis (FCP) as
      well as Indian patients with tropical calcific pancreatitis (TCP). METHODS:
      Patients and controls were screened by means of previously described quantitative
      fluorescent multiplex polymerase chain reaction and/or genotyping of the
      microsatellite marker rs3222967. RESULTS: The approximately 605 kilobase
      triplication and a novel duplication (confirmed by fluorescence in situ
      hybridization) of the trypsinogen locus were detected in 10 and 2 of 202 ICP
      patients, respectively (age of disease onset, <or=20 years) but were absent in
      282 French controls. In addition, the duplication mutation was found in 2 of 1044
      ICP patients whose age of disease onset was >20 years. However, the 2 trypsinogen
      copy number mutations were observed in neither 103 FCP patients nor 268 Indian
      TCP patients. CONCLUSIONS: Our findings revealed the molecular basis of 6% of the
      young ICP patients and further demonstrated that chronic pancreatitis is a
      genomic disorder. Our findings also add to the mounting evidence showing that
      trypsinogen gene mutations do not appear to play an important role in the
      pathogenesis of TCP in the Indian population. Finally, a dividend of this study
      is that we have provided convincing evidence to show that all 5 previously
      described copy number variations involving PRSS1 or/and PRSS2 are artifacts.

PMID- 18063423
TI  - The incidence of arterial thromboembolic diseases in inflammatory bowel disease:
      a population-based study.
AB  - BACKGROUND & AIMS: We aimed to determine if there was an increased risk for
      arterial thromboembolic diseases (ATED) in inflammatory bowel disease (IBD).
      METHODS: We used the University of Manitoba IBD Epidemiology Database (1984-2003)
      (n = 8060), and a matched cohort (n = 80,489) drawn from the Manitoba Health
      administrative database. Each IBD case and non-IBD control has a unique personal
      health identification number and each health system encounter is identified by a
      diagnostic code (International Classification of Diseases, 9th revision [ICD-9]).
      We compared the IBD with the non-IBD cohorts for the incidence of ATED events
      following the index case diagnosis of IBD including: ischemic heart disease (ICD
      9-Clinical Modification [CM] codes 410-414.x), cerebrovascular disease (ICD-9-CM
      codes 430-436.x), and undifferentiated ATED (ICD-9-CM codes 440.x and 445.x). The
      incidence rate of 1 episode or more of these diseases was assessed in relation to
      the individual person-years of follow-up evaluation. Incidence rates and
      incidence rate ratios (IRRs) were computed for all IBD, and stratified by IBD
      diagnosis, sex, and age. RESULTS: For ischemic heart disease, risk was increased
      for all IBD (IRR, 1.26; 95% confidence interval [CI], 1.11-1.44) and was
      increased for Crohn's disease and ulcerative colitis in both, males and females.
      For cerebrovascular disease, only Crohn's disease was associated with increased
      risk (IRR, 1.32; 95% CI, 1.05-1.66), and for undifferentiated ATED only females
      (IRR, 1.96; 95% CI, 1.24-3.10) and those aged 0 to 39 years (IRR, 19.95; 95% CI,
      1.81-219.92) and 40 to 59 years (IRR, 3.17; 95% CI, 1.27-7.91) had significantly
      increased risks. CONCLUSIONS: IBD patients are more likely to have cardiac ATED,
      regardless of diagnosis or sex. Crohn's disease has an increased risk for
      cerebral ATED. Smoking, the prothrombotic aspect of systemic inflammation, or a
      genetic predisposition may contribute to the risk.

PMID- 18063424
TI  - Topography of the porcine epicardiac nerve plexus as revealed by histochemistry
      for acetylcholinesterase.
AB  - The aim of the present study was to map the topography of the porcine epicardiac
      nerve plexus (ENP) and to re-examine the total number and distribution of the
      porcine intracardiac ganglia and neurons. Eleven juvenile pigs (Sus scrofa
      domestica, 3-4 weeks of age) were examined employing histochemistry for
      acetylcholinesterase to reveal the ENP on total hearts. The nerves entered
      porcine epicardium at five sites: (1) ventro-medially to the origin of the
      superior vena cava, (2) dorsally to the origin of the superior vena cava, (3)
      among the pulmonary veins, (4) dorso-medially to the origin of the left azygos
      vein, and (5) ventrally to the left pulmonary vein. Within the porcine
      epicardium, the nerves connected to the groups of the intrinsic ganglia and
      proceeded into the discrete atrial and ventricular regions via five topographical
      pathways (subplexuses). In general, the porcine left atrium received nerves by
      four subplexuses, left ventricle by three subplexuses, right atrium and right
      ventricle each by two subplexuses. The estimated total number of the intrinsic
      ganglia per porcine heart was 362+/-52. About 55% of ganglia per porcine heart
      were accumulated on the left atrium while 36% on the right atrium. The percentage
      of ganglia within porcine ventricular and para-aortic regions was 7.6% and 1.6%,
      respectively. On average, porcine heart contained about 12,000 intrinsic neurons.
      In summary, the results of the present study imply that (1) the porcine
      epicardiac nerves are grouped into distinct topographical pathways, and (2) the
      porcine atria contain significantly more intrinsic ganglia and neurons compared
      to the ventricles.

PMID- 18063426
TI  - Combination of HSCCC and Sephadex LH-20 methods An approach to isolation and
      purification of the main individual theaflavins from black tea.
AB  - In order to separate the main individual theaflavin monomers from black tea, high
      speed countercurrent chromatography (HSCCC) and Sephadex LH-20 column
      chromatography were applied. The results showed that theaflavin (TF1), theaflavin
      3-gallate (TF2A), theaflavin-3'-gallate (TF2B) and theaflavin-3,3'-digallate
      (TF3) can be obtained by HSCCC using a solvent system composed of n-hexane-ethyl
      acetate-methanol-water (1:3:1:6, v/v/v/v), but the TF1 was containing epicatechin
      3-gallate (ECG). Similarly, Sephadex LH-20 can also effectively separate TF2A(B)
      and TF3, but epigallocatechin-3-gallate (EGCG) contaminated TF1, too. Combination
      of HSCCC and Sephadex LH-20, the preferably purified TF1, TF2A(B) and TF3 were
      obtained than single separation technique. In addition, ECG and EGCG were also
      suggested to be able to be comprehensively separated by combination of the two
      techniques.

PMID- 18063427
TI  - Cross species applicability of abundant protein depletion columns for ribulose
      1,5-bisphosphate carboxylase/oxygenase.
AB  - In plants, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is an
      important enzyme in the Calvin cycle, catalyzing the first step of carbon
      fixation. Because of its critical role in photosynthesis, RuBisCO comprises 30
      60% of the total protein content in green leaf tissue and represents a major
      protein which can interfere with determination of lower abundance proteins in
      plant proteomics. A potential solution to aid in the determination of low level
      proteins in plant proteomics are RuBisCO immunodepletion columns. Two formats,
      spin and LC, of Seppro IgY RuBisCO depletion columns were evaluated for cross
      species applicability. The spin and LC columns were found to deplete arabidopsis
      RuBisCO by greater than 90 and 98%, respectively, and automation could be
      achieved with the LC format. Canola RuBisCO was depleted to a similar extent, and
      there was evidence suggesting that corn and tobacco RuBisCO were also highly
      depleted in flow through fractions. Model proteins were spiked into samples to
      provide insight into the degree of non-specific binding. Finally, improved
      detection and identification of lower abundance proteins was demonstrated after
      depletion.

PMID- 18063428
TI  - Coeliac disease: oral ulcer prevalence, assessment of risk and association with
      gluten-free diet in children.
AB  - AIMS: Oral mucosal lesions may be markers of chronic gastrointestinal disorders,
      such as those causing malabsorption. Our objectives were to assess the prevalence
      of recurrent oral aphthous-like ulcers in coeliac disease patients living in the
      Mediterranean area, and to evaluate the impact of a gluten-free diet. METHODS: A
      test group of 269 patients (age range 3-17 years) with coeliac disease confirmed
      both serologically and histologically was compared with a control group of 575
      otherwise clinically healthy subjects for the presence, or a positive history of
      aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re
      evaluated 1-year after starting a gluten-free diet. RESULTS: Aphthous-like ulcers
      were found significantly more frequently in coeliac disease, in 22.7% (61/269) of
      patients with coeliac disease versus 7.1% (41/575) of controls (p=<0.0001; chi
      square=41.687; odds ratio=4.3123; 95% confidence interval=2.7664:6.722). Most
      coeliac disease patients with aphthous-like ulcers and adhering strictly to
      gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free
      diet, with no or reduced episodes of aphthous-like ulcers (p=0.0003; chi
      square=13.101; odds ratio=24.67; 95% confidence interval=2.63:231.441).
      CONCLUSIONS: The epidemiological association found between coeliac disease and
      aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be
      considered a risk indicator for coeliac disease, and that gluten-free diet leads
      to ulcer amelioration.

PMID- 18063429
TI  - Epithelial cell turnover, p53 and bcl-2 protein expression during oncogenesis of
      early and advanced gastric cancer in a Western population.
AB  - OBJECTIVES: To investigate epithelial cell turnover alterations, and p53, bcl-2
      protein expression during development of early and advanced gastric cancer in a
      Western population. METHODS: We investigated cell apoptosis and proliferation
      rates, p53 and bcl-2 protein expression in 17 early and 34 advanced gastric
      carcinomas and in the adjacent non-dysplastic mucosa. Cell proliferation, p53 and
      bcl-2 expression were detected immunohistochemically using MIB-1, anti-p53 and
      anti-bcl-2 monoclonal antibodies. Apoptosis was measured by TUNEL. The rate of
      the positive stained cells (labelling index) was count using image analysis
      technique. RESULTS: No difference was observed of either apoptotic (10 vs. 11) or
      proliferation (35 vs. 25) index between early and advanced cancers. However, the
      apoptotic index was significantly higher in intestinal type advanced tumors.
      While both apoptotic and proliferation indices were significantly higher in
      tumors than in the adjacent mucosa, no difference was observed of either
      apoptotic (2 vs. 2) or proliferation (8 vs. 13) index between the tissues
      adjacent to early and advanced tumors. p53 protein expression was significantly
      higher in advanced cancers (7 vs. 5, p=0.001) and in the non-dysplastic tissue
      adjacent to advanced tumors (3.5 vs. 2, p=0.001). bcl-2 labelling index was
      significantly higher in the mucosa adjacent to advanced carcinomas (15 vs. 5,
      p=0.016) but this difference did not reach significance in the tumors (20 vs. 15,
      p=0.37). CONCLUSIONS: Our data indicate similar cell turnover during
      tumorigenesis of early and advanced cancer. p53 and bcl-2 protein accumulation is
      more intense in gastric mucosa adjacent to advanced tumors and p53
      immunoreactivity peaks in advanced carcinomas.

PMID- 18063430
TI  - Development of Sr and CO3 co-substituted hydroxyapatites for biomedical
      applications.
AB  - Sr and CO3 co-substituted hydroxyapatite (SrCHA) nanopowder was synthesized by
      neutralization. The powder was characterized. The improved solubility in Hanks'
      balanced solution of SrCHA granules (400-600 microm of dimensional range),
      potentially usable as bone filler, was assessed and compared with that of an
      analogous carbonate free granulate. SrCHA porous bodies with interconnected micro
      and macro-porosity, which mimic the morphology of spongy bone, were prepared by
      the impregnation of cellulose sponges with suspensions of the SrCHA powder and
      controlled sintering. SrCHA porous scaffolds sintered at 850 degrees C, in
      flowing CO2 atmosphere, showed satisfying compressive strength (4.58+/-0.75 MPa)
      for a porosity value of 45 vol.% and retained the desired ionic substitutions
      (Sr/Ca=0.11 and CO3=6.8 wt.%). The possibility of widely modulating, by acting on
      the chemical-physical-geometrical features of the material, the prolonged in situ
      release of therapeutic Sr, together with the fundamental (Ca, PO4) and main
      substituting (CO3) ions that constitute the bone mineral phase, makes the use of
      SrCHA as resorbable bone filler or bone substitute scaffolds promising,
      especially when pathologies related with Sr deficiency are present. In vitro and
      in vivo tests are in progress.

PMID- 18063432
TI  - Reporting quality--the weakest link?

PMID- 18063433
TI  - Improving the reporting quality of randomised controlled trials in surgery.

PMID- 18063425
TI  - Using evolutionary tools to refine the new hypervariable region 3 within the
      envelope 2 protein of hepatitis C virus.
AB  - The envelope 2 protein of hepatitis C virus (HCV) presents three hypervariable
      regions, named HVR1, HVR2 and HVR3, in which the presence of antigenic sites has
      been described. Genetic variability in these regions may reflect the generation
      of escape mutants as a consequence of the immune response. Therefore, these
      regions would tend to accumulate amino acid changes along the infection process,
      an effect that could be accelerated by antiviral treatments. In this study, we
      have analyzed the E1-E2 region of 23 HCV patients non-responders to antiviral
      treatment, 7 of which were infected with subtype 1a, 15 with subtype 1b, and 1
      with a new HCV-1 subtype, before and after 6 and/or 12 months of peg
      interferon+ribavirin treatment. We have sequenced about 100 clones from each
      sample, analyzing a total of 4906 sequences. A detailed analysis of the
      evolutionary forces acting along the genome region studied confirmed the
      existence of the three hypervariable regions, characterized by significant
      changes in amino acid composition between samples taken at different times from
      the same patient and a high number of sites evolving under positive selection.
      Moreover, for the recently described HVR3, our results suggest that its location
      could be restricted to residues 434-450, instead of the originally postulated 431
      466.

PMID- 18063435
TI  - A chemical mutagenesis screen to identify modifier genes that interact with
      growth hormone and TGF-beta signaling pathways.
AB  - We describe a phenotype-driven mutagenesis screen in which mice carrying a
      targeted mutation are bred with ENU-treated males in order to provide a
      sensitized system for detecting dominant modifier mutations. The presence of
      initial mutation renders the screening system more responsive to subtle changes
      in modifier genes that would not be penetrant in an otherwise wild type
      background. We utilized two mutant mouse models: 1) mice carrying a mutation in
      growth hormone releasing hormone receptor (Ghrhr) (denoted 'lit' allele,
      Ghrhr(lit)), which results in GH deficiency; and 2) mice lacking Smad2 gene, a
      signal transducer for TGF-beta, an important bone growth factor. The Smad2(-/-)
      mice are lethal and Ghrhr(lit/lit) mice are dwarf, but both Smad2(+/-) and
      Ghrhr(lit/)(+) mice exhibit normal growth. We injected 6-7 weeks old C57BL/6J
      male mice with ENU (100 mg/kg dose) and bred them with Ghrhr(lit/)(+) and
      Smad2(+/-) mice. The F1 mice with Ghrhr(lit/)(+) or Smad2(+/-) genotype were
      screened for growth and skeletal phenotypes. An outlier was identified as >3 SD
      units different from wild type control (n=20-30). We screened about 100 F1 mice
      with Ghrhr(lit/)(+) and Smad2(+/-) genotypes and identified nine outliers. A
      backcross established heritability of three mutant lines in multiple generations.
      Among the phenotypic deviants, we have identified a mutant mouse with 30-40%
      reduced bone size. The magnitude of the bone size phenotype was amplified by the
      presence of one copy of the disrupted Ghrhr gene as determined by the 2-way ANOVA
      (p<0.02 for interaction). Thus, a new mouse model has been established to
      identify a gene that interacts with GH signaling to regulate bone size. In
      addition, the sensitized screen also demonstrated higher recovery of skeletal
      phenotypes as compared to that obtained in the classical ENU screen in wild type
      mice. The discovery of mutants in a selected pathway will provide a valuable tool
      to not only to discover novel genes involved in a particular process but will
      also prove useful for the elucidation of the biology of that process.

PMID- 18063434
TI  - Development of craniofacial structures in transgenic mice with constitutively
      active PTH/PTHrP receptor.
AB  - Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP)
      regulate calcium homeostasis, and PTHrP further regulates growth and development.
      A transgenic mouse carrying the constitutively active PTH/PTHrP receptor (HKrk
      H223R) under the control of the mouse bone and odontoblast-specific alpha1(I)
      collagen promoter (Col1-caPPR) has been developed to demonstrate the complex
      actions of this mutant receptor in hard tissue formation. We have further
      characterized Col1-caPPR mice abnormalities in the craniofacial region as a
      function of development. Col1-caPPR mice exhibited a delay in embryonic bone
      formation, followed by expansion of a number of craniofacial bones including the
      maxilla and mandible, delay in tooth eruption and teratosis, and a disrupted
      temporomandibular joint (TMJ). These findings suggest that the Col1-caPPR mouse
      is a useful model for characterization of the downstream effects of the
      constitutively active receptor during development and growth, and as a model for
      development of treatments of human diseases with similar characteristics.

PMID- 18063436
TI  - A unified theory for osteonal and hemi-osteonal remodeling.
AB  - The process of bone remodeling is carried out by 'basic multicellular units' of
      osteoclasts and osteoblasts. Osteoclasts excavate a resorption space that is
      subsequently filled with new bone by osteoblasts. In cortical bone osteoclasts
      dig tunnels through solid bone, in cancellous bone they dig trenches across the
      trabecular surface. Osteoblasts fill these tunnels and trenches, creating osteons
      and hemi-osteons, respectively. Both the osteons of cortical bone and the
      trabeculae of cancellous bone are aligned to the dominant loading direction,
      indicating that BMU's are mechanically regulated. How mechanical forces guide
      these cells is still uncertain. We hypothesize that strain-induced osteocyte
      signals inhibit osteoclast activity and stimulate osteoblast activity. This
      hypothesis was implemented in a finite element-based bone adaptation model, that
      was extended with a cell simulation model. This allowed us to examine tunneling
      and trenching by osteoclasts. We found that our simulations capture key features
      of BMU-based remodeling: (1) cortical BMU's create load-aligned osteons; (2)
      cancellous BMU's move across the surface of trabeculae instead of piercing them;
      (3) resorption-formation coupling occurs in response to strains around resorption
      sites; and (4) resorbing osteoclasts target nearby regions of osteocyte death,
      thus providing a mechanism for bone repair.

PMID- 18063437
TI  - Why eight EU Member States signed, but not yet ratified the Convention for Human
      Rights and Biomedicine.
AB  - The European Convention on Human Rights and Biomedicine was adopted by the
      Committee of Ministers of the Council of Europe on 19 November 1996 and opened
      for signature on 4 April 1997. At the moment 21 of the 33 countries that signed
      the Convention are EU Member States. Signing the Convention implies the
      obligation to put the Convention before the national Parliament within a
      reasonable period of time with a view to ratification. Eight of the 21 EU Member
      States--namely Finland, France, Italy, Latvia, Luxembourg, The Netherlands,
      Poland and Sweden - still have to complete the ratification. In this article the
      reasons why eight Member States have not yet ratified the Convention, but only
      signed it, are mapped and analyzed. Because of the concrete list of patient
      rights provided for in the Convention, we focus on the question whether the
      reasons for not ratifying are related to these patient rights provisions.

PMID- 18063438
TI  - How growth hormone controls growth, obesity and sexual dimorphism.
AB  - Understanding the molecular basis for the many actions of growth hormone (GH) has
      been challenging because many of these actions are only evident in vivo.
      Recently, STAT5b has emerged as a key GH signaling intermediate in the regulation
      of postnatal growth, adiposity and sexual dimorphism of hepatic gene expression.
      This realization is based on targeted disruption or mutation of the GH receptor
      and its signaling components, together with clinical studies of GH-insensitive
      mutants. Microarray analysis of liver from GH receptor and signal transducer and
      activation of transcription 5b (STAT5b)-deleted mice have identified a range of
      relevant transcripts regulated by the Janus kinase 2/STAT5b signaling pathway. In
      addition, many transcripts are regulated independently of STAT5b, presumably as a
      result of PtdIns 3-kinase, extracellular-regulated kinase and Src signaling by
      this pleiotropic cytokine receptor.

PMID- 18063439
TI  - A genetic legacy from archaic Homo.
AB  - The roles of fossil human populations in the origin of modern humans have been
      enigmatic. Earlier (archaic) human populations were biologically similar and were
      in recurrent temporal and geographic contact, making interbreeding between
      ancient populations likely. Regardless of the taxonomic status of these
      populations, adaptive alleles may have introgressed from archaic populations into
      modern humans. When an introgressed archaic allele has a selective advantage,
      even rare interbreeding can lead to its spread or fixation in later human
      populations. Several genetic loci are candidates for such introgression,
      including microcephalin, a gene influencing brain development. This example may
      suggest that the evolution of human cognition depended in part on the genetic
      legacy of archaic groups such as the Neanderthals.

PMID- 18063440
TI  - Telomerase activity in transthoracic fine-needle biopsy aspirates from non-small
      cell lung cancer as prognostic factor of patients' survival.
AB  - PURPOSE: Evaluation of the relationship between telomerase activity in
      transthoracic fine-needle biopsy (TFNB) aspirates collected from peripheral non
      small cell lung cancer (NSCLC), cancer advancement, risk of death and free of
      cancer recurrence survival. MATERIAL AND METHODS: The study group consisted of 93
      patients with peripheral infiltration of the lung. All of them had TFNB of the
      focal pulmonary lesion performed. The aspirates were subjected to standard
      cytological evaluation. Telomerase activity in the specimens was determined with
      the PCR-ELISA PLUS method. Cancer advancement, manner of treatment and survival
      were assessed in patients with NSCLC. RESULTS: A benign lesion of the lung was
      recognised in 14 cases. NSCLC was newly diagnosed in 79 subjects. Nobody with
      benign infiltration had a detectable level of telomerase in lung infiltration.
      Increased telomerase activity was observed in 56 (70.9%) patients with lung
      cancer. It was significantly more often detected in patients with non-operable
      NSCLC (clinical stage IIIB plus IV) and patients with distant metastases (stage
      IV alone). Cox hazard analysis revealed that presence of telomerase activity in
      primary NSCLC is an independent prognostic factor of survival. Increased
      telomerase activity in TFNB aspirates was related to 7 times higher relative risk
      of death during the study [RR=6.9 (CI: 1.8-26.8); p<0.05] and 2.5 times higher
      risk of cancer recurrence after radical treatment [RR=2.5 (CI: 0.3-9.3); p<0.05].
      CONCLUSION: Telomerase activity in aspirates collected through TFNB of primary
      peripheral NSCLC could be a helpful independent prognostic factor of distant
      metastases and risk of death or cancer recurrence.

PMID- 18063441
TI  - Interaction of antibacterial peptides spanning the carboxy-terminal region of
      human beta-defensins 1-3 with phospholipids at the air-water interface and inner
      membrane of E. coli.
AB  - Synthetic peptides Phd1-3 spanning the cationic carboxy-terminal region of human
      beta-defensins HBD-1-3 have been shown to have antibacterial activity. Gross
      morphological changes were seen in E. coli cells treated with these peptides. In
      this paper, we have studied the surface-active properties of peptides Phd1-3 and
      their interactions with different phospholipids using Langmuir-Blodgett
      monolayers. Compression isotherms and increase in pressure on insertion of
      peptides into lipid monolayers at different initial pressures indicate the
      affinity of these peptides for negatively charged lipids. Phd3 inserted less
      effectively into monolayers as compared to Phd1 and Phd2. The peptides differed
      in their ability to permeabilize the inner membrane of E. coli, with Phd3 being
      least effective. It is likely that the peptides kill Gram-negative bacteria by
      more than one mechanism. When hydrophobicity and net charge favor insertion into
      lipid membranes, then membrane permeabilization could be the primary event in the
      killing of bacteria. In cases where membrane insertion does not occur,
      interaction with phospholipid interface induces highly selective stress that
      leads to stasis and cell death, as proposed for polymyxin B and bactenecin.

PMID- 18063442
TI  - Inhibition of astrocytic energy metabolism by D-lactate exposure impairs memory.
AB  - Bead discrimination learning in day-old chicken was inhibited by bilateral
      injection into the intermediate medial mesopallium (IMM), a homolog of the
      mammalian brain cortex, of the poorly metabolized enantiomer of L-lactate, D
      lactate. The window of vulnerability extended from 10 min before training to 20
      min after training. Unilateral injection 10 min before training inhibited only in
      the left IMM, whereas 10 min after training injection was only inhibitory if made
      into the right hemisphere. The pre-training administration caused memory loss
      from the earliest time tested whereas memory was maintained for another 20 min
      when D-lactate was injected 10 min post-training. The ability of acetate, an
      astrocyte-specific substrate, injected into the IMM to counteract the inhibitory
      effect was tested. Following D-lactate injection 10 min before training, rescue
      of memory immediately after training was achieved by acetate as long as
      aspartate, an oxaloacetate precursor, was also present. This suggests that
      pyruvate carboxylation is necessary for net synthesis of glutamate, which is
      known to occur at this time [Gibbs, M.E., Lloyd, H.G.E., Santa, T., Hertz, L.,
      2007. Glycogen is a preferred glutamate precursor during learning in 1-day-old
      chick: biochemical and behavioral evidence. J. Neurosci. Res., 85, 3326-3333].
      However, acetate alone rescued memory 20 min post-training (following d-lactate
      injection 10 min after training), indicating that pyruvate at this time is used
      for energy production, consistent with memory inhibition by dinitrophenol. These
      findings suggest that D-lactate acts by inhibiting uptake of L-lactate into
      astrocytes (an extracellular effect) or metabolism of pyruvate in astrocytic
      mitochondria (an intracellular effect). An apparent lag phase between the
      administration of d-lactate and its inhibition of learning favors the latter
      possibility. Thus, under the present experimental conditions D-lactate acts as an
      astrocytic metabolic inhibitor rather than as an inhibitor of neuronal L-lactate
      uptake, as has occasionally been suggested. Analogously, a rare reversible
      neurological syndrome with memory deficits, D-lactate encephalopathy, may mainly
      or exclusively be due to astrocytic malfunction.

PMID- 18063443
TI  - Synthesis and anti-inflammatory activity evaluation of unsymmetrical selenides.
AB  - The alkylation reaction of 2,2'-diseleno and 4,4'-diseleno-bis(benzoic acid)
      derivatives in the presence of sodium borohydride and alkyl halides allowed the
      synthesis of various new o- and p-alkylselenenylated benzoic acid derivatives in
      good yields. The anti-inflammatory activity of selected selenide derivatives on
      granuloma induced by subcutaneous implantation of cotton pellets in Wistar rats
      was examined. Selenium derivatives 2a, 2c and 2e showed anti-inflammatory
      activity although to a lesser extent as compared to indomethacin, however they
      were found less toxic than the latter.

PMID- 18063444
TI  - Improvement in the quality of the catering service of a rehabilitation hospital.
AB  - BACKGROUND: Malnutrition due to undernutrition or overnutrition is highly
      prevalent in hospital in-patients and it decisively conditions patients clinical
      outcome. One of the most influencing factors of malnutrition in hospitalized
      patients is--at least in part--the Catering Service Quality. AIM: Is to verify,
      over a 5 year period, the course of the quality of the institutional Catering
      Service, verifying the effectiveness of the quality improvement process used.
      METHODS: Quality control was performed by objective (meal order accuracy, proper
      distribution of food in trolleys, route time from the kitchen to the ward and
      time of food distribution, food weight and temperature, waste assessment) and
      subjective assessment (quality was measured by giving the patients a
      questionnaire after meals). RESULTS: The survey included: 572 meals and 591
      interviews. A significant amount of "qualitative" errors (lack of respect for
      patient preferences or at the moment of supplying the food trolley) have been
      found. Over the time and the amount of patients that wasted a considerable amount
      of the portion served was considerably reduced food temperature have been
      improved. Also patient satisfaction with menu variability, portion size,
      temperature and cooking quality improved over time. The overall ratings of meals
      under observation improved too in fact, positive opinions ranged from 18% in 2002
      to 48.3% in 2006. CONCLUSION: Ongoing research and quality verification, which
      include all catering service workers, yields a constant improvement in quality.
      Patients in healthcare settings should receive a service they appreciates, but it
      should be--at the same time--correct from a nutritional point of view. For this
      reason, it is necessary a continuous mediation between customers satisfaction and
      nutritionists work, dieticians and nursing staff. From this point of view the
      educational approach becomes essential to feed patient compliance to dietetic
      treatment that will continue after discharge.

PMID- 18063446
TI  - Antibody induction by virosomal, MF59-adjuvanted, or conventional influenza
      vaccines in the elderly.
AB  - In a randomized, observer-blind, three-arm, parallel group, multi-centre trial
      including 386 elderly subjects in four countries, the immunogenicity and safety
      was studied of three different trivalent inactivated surface antigen (subunit)
      influenza vaccine types: a conventional subunit influenza vaccine (SIV, brand:
      Influvac and two newer vaccines: a MF59-adjuvanted subunit influenza vaccine
      (adSIV, brand: Fluad and a virosomal subunit influenza vaccine (vSIV, brand:
      Invivac. All vaccines were trivalent containing 15 microg hemagglutinin of each
      virus strain as recommended by the World Health Organization for the 2004-2005
      season. The study was designed to demonstrate the serological non-inferiority of
      vSIV to both adSIV and SIV in elderly persons. The secondary objective was to
      investigate whether vSIV is superior to adSIV with respect to local
      reactogenicity. For all three vaccine strains, the post-vaccination geometric
      mean titres were comparable between SIV and adSIV and between vSIV and SIV.
      Seroprotection rates (i.e. percentages of subjects with a post-vaccination titre
      >or=40) varied between 84.1-100% indicating that the three vaccines all induced a
      strong antibody response. Local and systemic reactions were more frequently
      associated with adSIV (46 and 32%, respectively) than with vSIV or SIV (
      approximately 20%). Vaccinations caused only little inconvenience as measured by
      questionnaire. In general, all vaccines were safe and well tolerated. In this
      trial, virosomal vaccine had similar immunogenicity to MF59-adjuvanted and
      conventional subunit vaccine and was considerably less reactogenic than the MF59
      adjuvanted vaccine in the elderly.

PMID- 18063445
TI  - A synthetic triacylated pseudo-dipeptide molecule promotes Th1/TReg immune
      responses and enhances tolerance induction via the sublingual route.
AB  - In this study, we tested two triacylated pseudo-dipeptidic molecules, OM-197-MP
      AC and OM-294-BA-MP as candidate adjuvants for allergy vaccines. Both molecules
      induce human dendritic cell (h-DC) maturation and polarize naive T cells toward
      the Th1 type with IFNgamma production. Only OM-294-BA-MP induces IL10 gene
      expression both in monocyte-derived DCs and CD4+ naive T cells. Sublingual
      administration of OM-294-BA-MP plus the antigen enhances tolerance induction in
      BALB/c mice with established asthma to ovalbumin with an impact on both airways
      hyperresponsiveness and lung inflammation. Given its Th1/Treg polarizing
      properties, OM-294-BA-MP is a valid candidate for sublingual allergy vaccines.

PMID- 18063447
TI  - Humoral immunity targeting site I of antigenic domain 2 of glycoprotein B upon
      immunization with different cytomegalovirus candidate vaccines.
AB  - Glycoprotein B (gB) is a major component in several vaccines that are under
      development for prevention of disease by cytomegalovirus. It contains multiple
      determinants that are targets for neutralizing antibodies. One of them is site I
      of antigenic domain 2 (AD-2). The epitope, defined by short peptides, is quite
      conserved between different isolates. However, it is poorly immunogenic in
      natural infection. In this study we investigated the extent to which different
      vaccines, attenuated live Towne vaccine with or without priming with a canarypox
      virus coding for gB, or a recombinant gB vaccine adjuvanted with MF59, induced
      antibodies to this epitope. As in natural infection only a fraction of all
      subjects developed antibody responses against site I of AD-2 following
      vaccination. We suggest that strategies that enhance immunogenicity of this
      epitope will improve vaccine efficacy.

PMID- 18063448
TI  - In vivo oral administration effects of various oligodeoxynucleotides containing
      synthetic immunostimulatory motifs in the immune response to pseudorabies
      attenuated virus vaccine in newborn piglets.
AB  - Numerous studies have demonstrated that oligonucleotides containing CpG motifs
      (CpG ODN) are efficient immunoadjuvants to various antigens administered by
      parenteral routes to mice. Recently, it has been found that CpG ODNs also is a
      promising mucosal adjuvant in mice. To date, there have been no studies to screen
      the optimal CpG sequence and modified ODN backbone to piglets in vivo, when
      delivered by oral route. We have previously demonstrated that human-specific CpG
      ODN is a potent adjuvant to pseudorabies live attenuated virus (PRV) vaccine when
      administered subcutaneously (SC) or ocularly in piglets. In this study, we
      screened and evaluated the optimal CpG sequences (porcine-specific, human
      specific, mouse-specific ODN) and optimal backbone (SOS-backbone consisting of a
      nuclease-resistant phosphorothioate guanosines at the 5' and the 3'-end and with
      a phosphodiester (O) in the center and phosphorothioate (S) backbone (S
      backbone)) to PRV vaccine delivered orally in piglets. The proliferation of
      peripheral blood mononuclear cells (PBMCs), IFN-gamma and IL-4 in serum, and the
      titre of IgG, IgG2/IgG1 isotype in serum and IgA in intestinal washings and feces
      to PRV vaccine were tested at different time-points. The results suggested that,
      CpG ODNs augmented systemic (IgG in serum, T-cell proliferation) and mucosal (IgA
      in intestinal washings and feces) immune responses against antigen. CpG ODNs
      stimulated both T-helper type1 (Th1) (IgG2) and Th2 (IgA) responses when
      delivered orally. With the same backbone, the porcine-specific ODN-induced
      responses were comparable with human-specific ODNs, but stronger than mouse
      specific CpG ODNs. SOS-backbone induced a stronger IFN-gamma and proliferative
      responses than S-backbone, while antibody responses induced by SOS-backbones were
      slightly less or similar with S-backbone. The in vivo data demonstrate for the
      first time that porcine-specific and human-specific ODNs both are optimal
      sequences for mucosal system in piglets.

PMID- 18063449
TI  - Recombinant Mycobacterium bovis BCG expressing the LipL32 antigen of Leptospira
      interrogans protects hamsters from challenge.
AB  - The bacillus Calmette--Guerin (BCG), a live attenuated Mycobacterium bovis strain
      is considered a promising candidate as a vector system for delivery of foreign
      antigens to the immune system. The gene coding for the Leptospira interrogans
      external membrane protein LipL32, a highly immunogenic antigen found in all
      pathogenic leptospira, was cloned into several mycobacterial vectors for
      expression in BCG. Hamsters immunized with recombinant BCG (rBCG) expressing
      LipL32 were protected against mortality (P<or=0.05) upon challenge with a lethal
      inoculum of L. interrogans serovar Copenhageni. Autopsy examination did not
      reveal macroscopic or histological evidence of disease in rBCG immunized hamsters
      that survived lethal challenge. The data presented here further enhance the
      status of LipL32 as a promising candidate antigen for use in the control of
      leptospirosis, when presented to the immune system by an appropriate delivery
      system.

PMID- 18063451
TI  - Radionuclide (RN) pollution is a worldwide problem that arises from human
      activities.

PMID- 18063450
TI  - Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric
      coated capsules.
AB  - Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds
      potential for mucosal immunization, particularly against mucosal pathogens like
      the human immunodeficiency virus (HIV). Among the different strategies for
      achieving targeted release in the GI tract, namely the small intestine, pH
      sensitive enteric coating polymers have been shown to protect solid oral dosage
      forms from the harsh digestive environment of the stomach and dissolve relatively
      rapidly in the small intestine by taking advantage of the luminal pH gradient. We
      developed an enteric polymethacrylate formulation for coating hydroxy-propyl
      methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5)
      vectors expressing HIV-1 gag and a string of six highly-conserved HIV-1 envelope
      peptides representing broadly cross-reactive CD4(+) and CD8(+) T cell epitopes.
      Oral immunization of rhesus macaques with these capsules primed antigen-specific
      mucosal and systemic immune responses and subsequent intranasal delivery of the
      envelope peptide cocktail using a mutant cholera toxin adjuvant boosted cellular
      immune responses including, antigen-specific intracellular IFN-gamma-producing
      CD4(+) and CD8(+) effector memory T cells in the intestine. These results suggest
      that the combination of oral adenoviral vector priming followed by intranasal
      protein/peptide boosting may be an effective mucosal HIV vaccination strategy for
      targeting viral antigens to the GI tract and priming systemic and mucosal
      immunity.

PMID- 18063452
TI  - Increase in volume of dental local anaesthetic solution while maintaining the
      tissue lidocaine and adrenaline concentration does not increase acute
      postoperative pain after gingivectomy.
AB  - A randomised, single-blind, within-patient, crossover study was done in 45
      patients (29 women and 16 men, mean age 49 years, range 37-71) who had bilateral
      "identical" gingivectomies. On one occasion a standard volume of local
      anaesthetic containing 2% lidocaine and 1/80,000 adrenaline was infiltrated into
      the mucosal tissue before operation. On the other, double the standard volume
      with 1% lidocaine and 1/160,000 adrenaline was infiltrated. The intensity of
      postoperative pain was recorded by the patients on a 100 mm visual analogue scale
      every hour for an 11-hour observation period. The time courses and the sum of
      pain intensity after injection of the double and standard volumes did not differ
      significantly. Doubling the volume of local anaesthetic while maintaining the
      total lidocaine and adrenaline concentration that was infiltrated does not
      influence the intensity of acute pain after gingivectomy.

PMID- 18063453
TI  - Osseointegrated implants: a potential route of entry for squamous cell carcinoma
      of the mandible.
AB  - Documented cases of oral squamous cell carcinoma in relation to osseointegrated
      implants are rare. We present the first case with evidence to suggest that
      implants provide a route of entry for squamous cell carcinoma to the mandible.

PMID- 18063454
TI  - Re: Visavadia BG, Honeysett J, Danford MH. Manuka honey dressing: an effective
      treatment for chronic wound infections. Br J Oral Maxillofac Surg. 2006 Nov 17;
      [Epub ahead of print].

PMID- 18063455
TI  - Maxillofacial surgical trauma--management on a day-stay basis.

PMID- 18063456
TI  - Risk factors for a bad split during sagittal split osteotomy.
AB  - One of the operative complications during sagittal split osteotomy (SSO) in
      orthognatic surgery is a bad split, meaning an undesired fracture of the mandible
      during osteotomy. The aim of this study was to find out if there is a relation
      between the occurrence of bad splits during SSO and the presence of third molars,
      the patient's age, or the surgeon's experience. Clinical notes of 110 consecutive
      patients who had had a total of 220 SSOs using the Obwegeser/Dal Pont technique
      were evaluated and divided into three groups: 1 missing third molar (n=168); 2
      retained or impacted third molar that was removed during the SSO (n=23); and 3
      third molar left in place during SSO (n=29). There were a total of 12 (6%) bad
      splits. 9 (5%) in group 1, two (9%) in group 2, and one (3%) in group 3. There
      were no significant differences between groups 1-3, in particular the surgeon's
      qualification had no influence on the incidence. Older patients seemed more at
      risk of a bad split than younger ones.

PMID- 18063457
TI  - Biomechanical evaluation of rotator cuff repairs in a sheep model: suture anchors
      using arthroscopic Mason-Allen stitches compared with transosseous sutures using
      traditional modified Mason-Allen stitches.
AB  - BACKGROUND: The optimal method for rotator cuff repair of the shoulder is not yet
      known. The aim of this study was to compare the time-dependent biomechanical
      properties of the traditional open transosseous suture technique and modified
      Mason-Allen stitches (group 1) versus the double-loaded suture anchors technique
      and so-called arthroscopic Mason-Allen stitches (group 2) in rotator cuff repair.
      METHODS: Eighteen adult female sheep were randomized into two groups: in an open
      approach in which the released infraspinatus tendon was repaired with group 1,
      and with group 2. Animals were sacrificed at 6, 12, or 26 weeks; shoulders were
      harvested and magnetic resonance imaging was performed. Eight untreated
      contralateral shoulders served as controls. Tendons of 16 additional unpaired
      cadaver shoulder joints of adult female sheep were identically treated for
      analysis at time zero. In a biomechanical evaluation all specimens were loaded to
      failure at a constant displacement rate using a standard universal testing
      machine. The load-to-failure and stiffness of the healed bone-tendon interface
      were calculated. RESULTS: Magnetic resonance imaging analysis showed cuff
      integrity in all cases, and no evidence of foreign body reaction to the anchors.
      Load-to-failure and stiffness data did not indicate any significant difference
      between the two treatment groups, neither at 6 weeks nor at 12 or 26 weeks.
      However, at time zero the group 2 had a higher load-to-failure in comparison to
      the group 1 (P<0.010), but there was no difference for the stiffness (P<0.121).
      CONCLUSIONS: This in vivo study showed that, postoperatively, the group 2
      technique provides superior stability and after healing would gain strength
      comparable to the group 1 technique.

PMID- 18063458
TI  - The identification of age-related differences in kinetic gait parameters using
      principal component analysis.
AB  - Background. The age of onset of adult-like kinetic gait patterns is
      controversial. A potential cause of discrepant results between studies is the
      statistical analyses used to test for differences in kinetic parameters between
      age groups. Therefore, the purpose of this study was to identify age-related
      differences in kinetic gait parameters across children aged 3-13 years using
      principal component analysis. Methods. Principal component analysis was applied
      to seven kinetic waveform variables (N=7) from each of four age groups (3-4 years
      (n=13); 5-6 years (n=10); 7-8 years (n=12); and 9-13 years (n=12)). The principal
      component scores for each kinetic variable were used to test for group
      differences using one-way ANOVA and Kruskal-Wallis tests. Findings. Significant
      group differences (P<0.05) were found for five of the principal component scores.
      Plantarflexion moments increased with age and the oldest group of children (9-13
      years old) demonstrated significantly larger plantarflexor moment patterns
      compared to all other age groups. The 9-13 years old showed significantly larger
      knee flexor and extensor moments for the first half of the cycle and a later
      reversal to extensor moments in terminal stance compared to 3-6 years old. The
      older group also showed decreased hip extensor moments for the first third of the
      cycle and increased flexor moments in the second third of the cycle compared to
      the 3-4 and 7-8 years old. Larger stance phase hip abduction moments were
      observed in the older group compared to all other groups. This was followed by a
      more complex pattern of alternating moments. Hip power also showed a complex
      series of differences between age-groups. Interpretation. Compared to
      parameterization techniques, principal component analysis identified different
      characteristics in kinetic gait data to discriminate between paediatric age
      groups. This is the first study to identify age-related differences in gait
      kinetics using waveform analysis.

PMID- 18063460
TI  - Tissue distribution of organochlorine pesticides in fish collected from the Pearl
      River Delta, China: implications for fishery input source and bioaccumulation.
AB  - Fish tissues from different fishery types (freshwater farmed, seawater farmed and
      seawater wild) were analyzed for organochlorine pesticides (OCPs), with the aim
      to further our understanding of bioaccumulation, and reflect the state of
      different fishery environments. Significantly higher SigmaOCP levels were found
      in seawater farmed fish than others, and among three freshwater farmed species,
      the lowest levels occurred in filter-feeding fish (bighead carp). Liver contained
      the highest SigmaOCP levels, while no significant differences were found among
      other tissues. Among DDT components, p,p'-DDT was abundant in seawater fish,
      while for freshwater fish, p,p'-DDE was the predominant congeners, except for
      northern snakehead (34% for p,p'-DDE and 30% for p,p'-DDT). The new source of
      DDTs to freshwater fish ponds was partly attributed to dicofol, whereas sewage
      discharged from the Pearl River Delta and anti-fouling paint were likely the DDTs
      sources to seawater farmed fish.

PMID- 18063459
TI  - Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria.
AB  - PNH is an uncommon acquired hemolytic anemia that often manifests with
      hemoglobinuria, abdominal pain, smooth muscle dystonias, fatigue, and thrombosis.
      The disease results from the expansion of hematopoietic stem cells harboring a
      mutation in a gene, PIG-A, that is required for the biosynthesis of a lipid
      moiety, glycosylphosphatidylinositol (GPI), that attaches dozens of different
      proteins to the cell surface. Thus, PNH cells are deficient in cell surface GPI
      anchored proteins; this deficiency on erythrocytes leads to intravascular
      hemolysis since certain GPI anchored proteins normally function as complement
      regulators. Free hemoglobin released from intravascular hemolysis leads to
      circulating nitric oxide depletion and is responsible for many of the clinical
      manifestations of PNH, including fatigue, erectile dysfunction, esophageal spasm,
      and thrombosis. Interestingly, rare PIG-A mutations can be found in virtually all
      healthy control subjects leading to speculation that PIG-A mutations in
      hematopoietic stem cells are common benign events. However, recent data reveals
      that most of these mutations in healthy controls are not derived from stem cells.
      The recently FDA approved complement inhibitor eculizumab has been shown to
      decrease hemolysis, decrease erythrocyte transfusion requirements, decrease the
      risk for thrombosis and improve quality of life for PNH patients.

PMID- 18063461
TI  - Indole-3-carbinol (I3C) exhibits inhibitory and preventive effects on prostate
      tumors in mice.
AB  - Prostate cancer (PC) is the most commonly diagnosed malignancy for men in Western
      countries. Research showed that cruciferous vegetables containing indole
      derivatives were involved in cancer prevention. This study was designed to
      investigate the effect of indole-3-carbinol (I3C) in cell lines and on PC tumor
      growth in mice when given as a therapeutic and as a preventive treatment. The
      effect in vitro of 13C on the viability, proliferation and apoptosis of mouse PC
      cell line TRAMP-C2 and on bovine capillary endothelial (BCE) cells was examined
      using MTT, BrdU and FACS analyses. The effect of I3C (20 mg/kg body weight) as
      both a therapeutic and a preventive treatment on the growth of PC cells,
      inoculated subcutaneously in C57BL/6 mice, was evaluated using tumor volume
      measurements and immunohistochemistry. I3C decreased the proliferation rate in 3
      folds (staining to Ki-67), and promoted apoptosis (staining with caspase 3). I3C,
      injected intraperitonially (I.P.), significantly inhibited the tumor growth (a
      78% decrease in tumor volume) and affected the angiogenesis process by decreasing
      the microvessel density (CD31 endothelial marker) and complexity. I3C has a
      significant inhibitory effect on PC cells in vitro and in vivo, and offers a
      potential usage as both preventive and therapeutic agent for humans.

PMID- 18063462
TI  - Differential expression of neuronal and inducible nitric oxide synthase in rat
      brain after subchronic administration of 3-monochloro-1,2-propanediol.
AB  - The compound 3-monochloro-1,2-propanediol (3-MCPD) is a contaminant of acid
      hydrolyzed vegetable protein foodstuffs. Several reports have suggested that
      chronic exposure to 3-MCPD can produce neurotoxicity or neurobehavioral effects
      in experimental animals. We sought to further explore the neurotoxic effects of 3
      MCPD (10 or 30 mg/kg) administered for 13 weeks on the expression of two forms of
      nitric oxide synthase (NOS), neuronal NOS (nNOS), and inducible NOS (iNOS), in
      rat cerebral cortex and striatum. Using immunocytochemistry, the number of nNOS
      expressing neurons or the optical density of iNOS staining in sections from three
      coronal levels (bregma 1.0, -0.4, and -2.3 mm) were compared between 3-MCPD
      treated and control rats. At bregma level 1.0 mm, the number of nNOS-expressing
      neurons was significantly decreased in the 10 and 30 mg/kg groups. At bregma
      level -0.4 mm, nNOS expression was significantly decreased only in the 30 mg/kg
      group, in the cortex and striatum. However, at bregma level -2.3 mm, 3-MCPD
      administration produced no significant difference in the number of nNOS
      expressing neurons in the cortex or striatum. In contrast, iNOS expression was
      significantly increased in the neocortex and striatum at all three rostrocaudal
      levels following subchronic 3-MCPD administration. These data suggest that
      subchronic 3-MCPD exposure may involve compensatory mechanisms acting on nNOS and
      iNOS expression to maintain nitric oxide homeostasis in the rostral part of the
      neocortex and striatum. However, in the caudal brain, increased iNOS expression
      did not profoundly suppress nNOS expression. Thus, the present study suggests
      that 3-MCPD-induced neurotoxicity is mediated, at least in part, through
      disturbances in the nitric oxide signaling pathway and exhibits a rostrocaudal
      difference, through differential expression of nNOS and iNOS in the neocortex and
      striatum.

PMID- 18063463
TI  - DDVP markedly decreases the expression of granzyme B and granzyme 3/K in human NK
      cells.
AB  - Natural killer (NK), lymphokine-activated killer (LAK), and cytotoxic T
      lymphocyte (CTL) cells kill target cells by the directed release of cytolytic
      granules that contain perforin, granzymes, and granulysin. We have found
      previously that dimethyl 2,2-dichlorovinyl phosphate (DDVP, dichlorvos), an
      organophosphorus pesticide, significantly decreased the expression of perforin,
      granzyme A (GrA), and granulysin and inhibited NK, LAK, and CTL activities. To
      further explore the mechanism of organophosphorus pesticide-induced inhibition of
      cell-mediated cytolysis, we examined whether organophosphorus pesticides affect
      the expression of GrB and Gr3/K in NK cells. We used an interleukin-2 (IL-2)
      independent human NK cell line, NK-92CI. We confirmed that NK-92CI cells express
      intracellular GrB and Gr3/K by flow cytometry, that NK-92CI cells are highly
      cytotoxic to K562 cells with a chromium release assay, and that DDVP
      significantly inhibited cytolytic activity of NK-92CI cells in a dose- and time
      dependent manner. We found that DDVP significantly decreased the expression of
      GrB and Gr3/K in NK-92CI cells in a dose- and time-dependent manner by flow
      cytometry. Immunocytochemical results showed that DDVP significantly decreases
      the level of GrB positive granules in NK-92CI cells, which may be due to
      degranulation. Taken together, DDVP significantly inhibits NK activity and
      reduces the intracellular GrB and Gr3/K levels in NK cells.

PMID- 18063464
TI  - Cytotoxicity of 1,2-diacetylbenzene in human neuroblastoma SHSY5Y cells is
      mediated by oxidative stress.
AB  - Environmental substances or metabolites induce neuronal damage through oxidative
      stress. Environmental organic solvent metabolite, 1,2-diacetylbenzene (1,2-DAB),
      treated rats develop limb weakness with neuropathological damage in both the
      central and peripheral nervous systems. In this experiment, we examined the
      relevance of 1,2-DAB-induced toxicity to increased oxidative stress using human
      dopaminergic neuroblastoma SHSY5Y cells. 1,2-DAB (4, 16, and 32 microM) disrupted
      cytoskeletal integrity and caused morphological changes. 1,2-DAB significantly
      decreased cell viability and induced cell cycle arrest in the G(1) phase in a
      concentration-dependent manner. At higher concentration, it produced apoptosis.
      Pre-treatment of cells with the antioxidants, GSH or N-acetylcysteine (NAC),
      effectively blocked 1,2-DAB-mediated cytotoxicity including cell viability, and
      morphological changes. These results therefore suggest that oxidative stress is
      involved in environmental metabolite 1,2-DAB-mediated neurotoxicity and that
      antioxidant treatment can effectively protect the nervous system from
      environmental hazards.

PMID- 18063466
TI  - Olfaction and its dynamic influence on word and face processing: cross-modal
      integration.
AB  - The article specifies several important aspects related to the sense of smell in
      vertebrates. The idea that odors exert effects in the human brain though being
      not consciously perceived is introduced. Functional aspects related to cross
      modal sensory interaction between olfaction and vision are highlighted. In
      particular, studies making use of electrophysiological methods providing high
      temporal resolution reveal an early processing stage around 300 ms and a later
      stage around 700 ms after stimulus onset. The early stage has been associated
      with subconscious olfactory information processing, whereas the later stage most
      likely reflects conscious odor perception. Specific interactions are described
      between olfaction and language and between olfaction and face processing in
      correlation with both stages of olfactory information processing. A consciously
      perceived odor can negatively affect language and face processing if these
      stimuli are presented and associated simultaneously, whereas simultaneous
      subconscious odor processing has the potential to improve memory formation in
      other stimulus modalities. Strikingly, the subconscious effect seems not to
      depend on odor valence. Besides a better understanding of the sense of olfaction
      itself, these findings on cross-modal integration support the idea that neural
      representations exist for semantic contents (object meaning) independent from
      particular sensory modalities. These representations can be referred to as meta
      representations because the information they contain is derived from a great
      variety of sensory information integrated into a semantic representation of an
      object. It is suggested that such meta representations represent the basic units
      for cognition and that they provide inputs during dreaming.

PMID- 18063465
TI  - From bench to drug: human seizure modeling using Drosophila.
AB  - Studies of human seizure disorders have revealed that susceptibility to seizures
      is greatly influenced by genetic factors. In addition to causing epilepsy,
      genetic factors can suppress seizures and epileptogenesis. Examination of seizure
      suppressor genes is challenging in humans. However, such genes are readily
      identified and analyzed in a Drosophila animal model of epilepsy. In this
      article, the epilepsy phenotype of Drosophila seizure-sensitive mutants is
      reviewed. A novel class of genes called seizure-suppressors is described.
      Mutations defining suppressors revert the "epilepsy" phenotype of neurological
      mutants. We conclude this review with particular discussion of a seizure
      suppressor gene encoding DNA topoisomerase I (top1). Mutations of top1 are
      especially effective at reverting the seizure-sensitive phenotype of Drosophila
      epilepsy mutants. In addition, an unexpected class of anti-epileptic drugs has
      been identified. These are DNA topoisomerase I inhibitors such as camptothecin
      and its derivatives; several candidates are comparable or perhaps better than
      traditional anti-epileptic drugs such as valproate at reducing seizures in
      Drosophila drug-feeding experiments.

PMID- 18063467
TI  - Does dissociation of emotional and physiological reactivity predict blood
      pressure change at 3- and 10-year follow-up?
AB  - One of the major theories of psychosomatic medicine is that pervasive
      dissociations between physiological reactivity and simultaneous emotion awareness
      may be an important marker for the long-term development of cardiac problems.
      Subjective autonomic discrepancy (SAD) scores are proposed as a method of
      capturing the dissociation between physiological and emotional reactivity and
      increasing the explanatory power of predictive models of cardiac health outcomes.
      It was found that SAD scores for blood pressure indices show trait-like stability
      over a period of 3 years. Although linear 3-year prediction of systolic blood
      pressure came close to traditional definitions of significance, neither a linear
      nor a quadratic model was found to show significant prospective validity in
      predicting ambulatory blood pressure change over a 10-year period. Dissociation
      between physiological arousal and emotional awareness does not appear to be an
      important variable in the identification of individuals at risk for later
      cardiovascular health problems.

PMID- 18063468
TI  - Anticipation of affect in dysthymia: behavioral and neurophysiological
      indicators.
AB  - Anticipation for future affective events and prediction uncertainty were examined
      in healthy controls and individuals with dysthymia (DYS) using behavioral
      responses and the contingent negative variation (CNV) and post-imperative
      negative variation (PINV) event-related potential (ERP) components. Warning
      stimuli forecasted the valence of subsequently presented adjectives ("+",
      positive; "=", neutral; "-", negative), and participants indicated whether each
      adjective would describe them over the next two weeks. Controls expected fewer
      negative, and individuals with DYS expected fewer positive, adjectives to apply
      to them. CNV amplitudes were enhanced in controls prior to positive versus other
      adjectives. Response times and PINV amplitudes were greater following neutral
      compared to other adjectives, and PINV was larger overall in dysthymics compared
      to controls. In sum, healthy controls and individuals with DYS exhibit different
      behavioral and neurophysiological biases in anticipation for future affective
      events. These results are discussed in the context of cognitive theories of
      depression.

PMID- 18063469
TI  - Umbilical cord blood lactate: a valuable tool in the assessment of fetal
      metabolic acidosis.
AB  - OBJECTIVE: The aim of the present study was (1) to evaluate the relationship
      between umbilical cord arterial blood lactate and pH, standard base excess (SBE),
      and actual base excess (ABE) at delivery and (2) to suggest a cut-off level of
      umbilical cord arterial blood lactate in predicting fetal asphyxia using ROC
      curves, where an ABE value less than -12 was used as "gold standard" for
      significant intrapartum asphyxia. STUDY DESIGN: This is a descriptive study of
      umbilical cord arterial blood samples from 2554 singleton deliveries. The
      deliveries took place at the Department of Obstetrics and Gynaecology, Hvidovre
      University Hospital, Copenhagen, Denmark where umbilical cord blood sampling and
      blood gas analysis is part of the routine assessment of all newborns. RESULTS: We
      found significant correlations between lactate and pH (r=-0.73), lactate and SBE
      (r=-0.76), and lactate and ABE (r=-0.83). ROC-curves suggested a lactate cut-off
      level of 8mmol/l for indicating intrapartum asphyxia. CONCLUSION: Lactate in
      arterial umbilical cord blood might be a more direct and accordingly more correct
      indicator of fetal asphyxia at delivery than pH and SBE (or ABE). Its potential
      as a predictor of neonatal outcome needs to be evaluated in future studies.

PMID- 18063470
TI  - Craniopharyngioma: surgical experience of 309 cases in China.
AB  - OBJECTIVE: The objective of the present study was to retrospectively review the
      surgical outcome of 309 craniopharyngioma cases treated by a single neurosurgeon
      in China. PATIENTS AND METHODS: A total of 309 cases of craniopharyngioma that
      were treated surgically from January 1996 to May 2006. Among them, 162 (52.4%)
      patients were male and 147 (47.6%) were female. There were 259 (83.8%) patients
      older than 15 years (mean 35.8 years) and 50 (16.2%) younger than 15 years (mean
      8.8 years). The tumor size varied in diameter from 2.0 cm to 9.0 cm (mean 34.5
      mm). Pterional approach was performed in 211 (68.3%) cases, trans-laminal
      terminal approach through frontobasal interhemispheric fissure in 55 (17.8%)
      cases, subfrontal approach in 20 (6.5%) cases, and transcallosum approach into
      the anterior third ventricle in 11 (3.6%) cases. RESULTS: Total, subtotal, and
      partial removal of tumors were achieved in 276 (89.3%), 20 (6.5%), and 13 (4.2%)
      patients, respectively. The pituitary stalk was preserved in 186 (60.2%) cases,
      severed in 49 (15.9%) cases, and unidentified in 74 (23.9%) cases during surgery.
      There were 12 (3.9%) patients died within 1 month after surgery. A total of 204
      (66%) patients were followed from 6 months to 8 years (mean 2.1 years). In the
      167 patients with total tumor removal, 23 (13.7%) had tumor recurrence within an
      average of 1.8 years. While, in the 32 patients with subtotal or partial
      resection, 24 (75%) had recurrence within an average of 0.5 years. There were
      five deaths occurred during follow-up. CONCLUSION: Pre-surgery neuroimaging
      evaluations have improved our knowledge of intricate anatomical relationship
      between craniopharyngioma and the structures of the hypothalamus, pituitary
      stalk, and optic apparatus, which make total tumor resection feasible with the
      preservation of these vital structures to ensure a lower recurrence rate with
      acceptable mortality. However, excessive long-term morbidity, mostly related to
      hypopituitarism, which leads to the poor quality of life for the
      craniopharyngioma patients, is still remained. Further effort should be invested
      to monitor and maintain the normal hormone levels, hence improve the quality of
      life for craniopharyngioma patients.

PMID- 18063471
TI  - Short-term variability in amplitude and motor topography of whole-body
      involuntary movements in Parkinson's disease dyskinesias and in Huntington's
      chorea.
AB  - OBJECTIVES: Clinical observations have noted variability in amplitude of levodopa
      induced dyskinesias (LID) in Parkinson's disease (PD) and chorea in Huntington's
      disease (HD) during the day. However, no studies have examined whether both the
      amplitude and body location (motor topography) of whole-body involuntary movement
      (WBIM) varied over short periods of time (seconds or minutes), which may have a
      distinct and significant effect on how disruptive these WBIM may be. The present
      study quantified the variability of WBIM amplitude and motor topography in
      patients with PD having LID and in patients with HD having chorea. PATIENTS AND
      METHODS: WBIM was quantified using the MotionMonitor magnetic motion tracker
      system. Five patients in each group were tested in two conditions: sitting and
      standing. RESULTS: WBIM increased from sitting to standing, more so in choreic
      patients. WBIM varied from 17% to 102% of total WBIM amplitude. Chorea tended to
      present with greater variability than LID in absolute terms in the standing
      condition, but not when the mean WBIM amplitude was taken into consideration.
      Motor topography of WBIM also varied more in the HD group, but mostly in the
      seated condition where more limbs were free to move. Neither group expressed any
      laterality of involuntary movement, with amplitude being equally distributed on
      both sides of the body. CONCLUSION: Results show significant short-term
      variability in amplitude of chorea and LID, as well as, variability in location
      of these involuntary movements, illustrating the complexity of the adaptations
      required to live and be active with involuntary movements such as HD chorea or PD
      dyskinesias.

PMID- 18063472
TI  - Comparative study of oxidation of dye-Reactive Black B by different advanced
      oxidation processes: Fenton, electro-Fenton and photo-Fenton.
AB  - This study makes a comparison between photo-Fenton and a novel electro-Fenton
      called Fered-Fenton to study the mineralization of 10,000 mg/L of dye-Reactive
      Black B (RBB) aqueous solution, which was chosen as the model dye contaminant.
      Results indicate that the traditional Fenton process only yields 70%
      mineralization. This result can be improved by using Fered-Fenton to yield 93%
      mineralization resulting from the action of ferrous ion regenerated on the
      cathode. Furthermore, photo-Fenton allows a fast and more complete destruction of
      dye solutions and as a result of the action of ferrous ion regenerated by UV
      irradiation yields more than 98% mineralization. In all treatments, the RBB is
      rapidly decayed to some carboxylic acid intermediates. The major intermediates
      found are formic acid and oxalic acid. This study finds that formic acid can be
      completely mineralized by photo-Fenton, but its destruction is problematic using
      the Fenton method. Oxalic acid is much more difficult to treat than other organic
      acids. It could get further mineralization with the use of the Fered-Fenton
      process.

PMID- 18063473
TI  - Chromate reduction by Arthrobacter CR47 in biofilm packed bed reactors.
AB  - Bacterial strain Cr47 was isolated from a landfarming process soil sample. It was
      identified, by 16s rDNA sequencing, as Arthrobacter sp. The time course of the
      Cr(VI) reduction was monitored in batch operated packed bed biofilm reactors (12
      mL void volume) and in recirculating packed bed biofilm reactors (100 mL void
      volume) inoculated with bacterial strain Cr47. The reduction was evaluated with,
      30 mg L(-1) Cr(VI) laboratory solutions prepared with K2Cr2O7 and enriched with
      glucose-minimal medium, and with 30 mg L(-1) Cr(VI) industrial model solutions
      prepared with chrome plating waste waters enriched with sucrose-minimal medium.
      Under batch mode the reduction reaction by the biofilm seemed to fit well an
      exponential-decay model with a first order kinetic parameter of 0.071 mg(L h)(-1)
      Cr(VI). In the recirculating reactor, monitored after 4 weeks from inoculation
      and fed with laboratory solutions the removal rate was 0.79 mg(L h)(-1). In the
      reactor fed with the industrial model solutions the maximum Cr(VI) removal rate
      attained was 0.49 mg(L h)(-1). Artrobacter sp. packed bed biofilm reactors
      achieved Cr(VI) reduction rates comparable to other aerobic and anaerobic fixed
      film bioreactors previously reported.

PMID- 18063474
TI  - TGF-beta1 is increased in a transgenic mouse model of familial Alzheimer's
      disease and causes neuronal apoptosis.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder, due to excess amyloid
      beta peptide (Abeta). TGF-beta1 and beta-catenin signaling pathways have been
      separately implicated in modulating Abeta-neurotoxicity. However, the underlying
      mechanisms remain unclear. Here, we report that TGF-beta1 and nuclear Smad7 and
      beta-catenin levels were markedly upregulated in cortical brain regions of the
      TgCRND8 mice, a mouse model of familial Alzheimer's disease.
      Coimmunoprecipitation of cortical brain tissue lysates revealed an interaction
      between Smad7 and beta-catenin. This interaction which was significantly enhanced
      in the TgCRND8 mice was also associated with an increase in TCF/LEF DNA-shift
      binding activity. TCF/LEF reporter gene activity was significantly increased in
      mouse primary cortical neuronal cultures (MCN) from the TgCRND8 mice, compared to
      controls. Interestingly, exposure of MCN to Abeta(1-42) led to an increase in TGF
      beta1 and nuclear levels of both beta-catenin and Smad7. Furthermore, addition of
      TGF-beta1 to the MCN caused an increase in apoptosis and Smad7 levels. When Smad7
      or beta-catenin levels were reduced by siRNA, TGF-beta1-induced apoptosis was
      suppressed, indicating that both Smad7 and beta-catenin are required for TGF
      beta1-induced neurotoxicity. Since Abeta(1-42)-induced TGF-beta1, we suggest that
      TGF-beta1 may amplify Abeta(1-42)-mediated neurodegeneration in AD via Smad7 and
      beta-catenin interaction and nuclear localization.

PMID- 18063475
TI  - The sliding threshold of modification hypothesis: application to the effect of
      hypothyroidism or chronic psychosocial stress and nicotine on synaptic
      plasticity.
AB  - The Bienenstock, Cooper, and Munro (BCM) theory or the sliding threshold model
      can be used to explain the changes in synaptic plasticity related to learning and
      memory, namely long-term potentiation (LTP) and depression (LTD). In this study,
      we applied synaptic plasticity changes induced by either chronic psychosocial
      stress or hypothyroidism, and their restoration by chronic nicotine treatment, to
      the sliding threshold model. Psychosocial stress- or hypothyroidism-induced
      changes in synaptic plasticity generated a shift in the sliding threshold of
      modification (theta(m)) toward LTD. In addition, chronic nicotine treatment
      restored the theta(m) to the normal position by normalizing psychosocial stress-
      or hypothyroidism-induced impairment of LTP and enhancement of LTD. The data
      correlate with our previous findings: a shift in the balance of
      kinase/phosphatase toward phosphatase during psychosocial stress or
      hypothyroidism, which is restored by chronic nicotine treatment.

PMID- 18063476
TI  - Motor ontology in representing gaze-object relations.
AB  - Event-related functional magnetic resonance imaging (fMRI) was used to explore
      how the human brain models gaze-object relations. During scanning participants
      observed a human model gazing towards or away a target object presented either in
      isolation or flanked by a distractor object. In two further conditions the
      model's gaze was shifted and subsequently maintained away from the stimulus/i.
      These four conditions were implemented within a factorial design in which the
      main factors were "type of observed behavior" (gaze vs. gaze-away) and "context"
      (target alone vs. target flanked by a distractor). Results revealed that
      premotor, parietal and temporal areas, known to sub-serve the understanding of
      other people actions, were significantly more activated by the observation of the
      model gazing towards rather than away from the stimulus/i. In addition, a
      significant interaction indicated that, when the target was presented in
      isolation, neural activity within the inferior frontal gyrus, another key area
      for action understanding, was influenced by gaze-object relations. Our findings
      suggest that this area is important for the establishment of intentional gaze
      object relations and indicate that the presence of a distractor interferes with
      the representation of such relations.

PMID- 18063477
TI  - Induction of apoptosis signal-regulating kinase 1 and oxidative stress mediate
      age-dependent vulnerability to 3-nitropropionic acid in the mouse striatum.
AB  - The mitochondrial toxin, 3-nitropropionic acid (3-NP), produces age-dependent
      oxidative stress and selective striatal damage, which may simulate Huntington's
      disease starting in middle age. Recent reports showed that apoptosis signal
      regulating kinase 1 (Ask1) activated by oxidative stress triggers a cell death
      signaling pathway. 3-NP was injected to the striatum in C57BL/6J mice. We have
      confirmed that striatal lesion volume and DNA fragmentation were age-dependent
      after 3-NP treatment. In the non-injured striatum of the middle-aged group, the
      protein levels of Ask1 and its active form, phosphorylated Ask1 (pAsk1), were
      significantly higher than in the young group. Ask1 increased more in the 3-NP
      injured striatum of the middle-aged group than in the non-injured striatum, and
      subsequently the activity of pAsk1 was significantly higher than in the young
      group. However, middle-aged SOD1Tg mice showed significant reductions of Ask1 and
      pAsk1 in the injured and the non-injured striatum compared to the middle-aged
      group. In particular, apoptosis signal transduction and cell death were
      significantly inhibited by the reduction of Ask1 expression using siRNA. Present
      results suggest that age-related upregulation of Ask1 and oxidative stress may
      mediate age-dependent striatal vulnerability to 3-NP.

PMID- 18063478
TI  - Laser evoked responses to painful stimulation persist during sleep and predict
      subsequent arousals.
AB  - We studied behavioural responses and 32-channel brain potentials to nociceptive
      stimuli during all-night sleep in 12 healthy subjects, using sequences of thermal
      laser pulses delivered over the dorsum of the hand. Laser stimuli less than 20 dB
      over perception threshold had clear awakening properties, in accordance with the
      intrinsic threatening value of nociceptive signals. Even in cases where
      nociceptive stimulation did not interrupt sleep, it triggered motor responses in
      11% of trials. Only four subjects reported dreams, and on morning questionnaires
      there was no evidence of incorporation to dreams of nociceptive stimuli. Contrary
      to previous reports suggesting the absence of cortical nociceptive responses
      during sleep, we were able to record brain-evoked potentials to laser (LEPs)
      during all sleep stages. Sleep LEPs were in general attenuated, but their
      morphology was sleep-stage-dependent: in stage 2, the weakened initial response
      was often followed by a high-amplitude negative wave with typical features of a K
      complex. During paradoxical sleep (PS) LEP morphology was similar to that of
      waking, but frontal components showed strong attenuation, consistent with the
      reported frontal metabolic deactivation. A late positive component (450-650 ms)
      was recorded in both stage 2 and PS, the amplitude of which was significantly
      enhanced in trials that were followed by an arousal. This response appeared
      functionally related to the P3 wave, which in waking subjects has been associated
      to conscious perception and memory encoding.

PMID- 18063479
TI  - Loose ligation of the sciatic nerve is associated with TrkB receptor-dependent
      decreases in KCC2 protein levels in the ipsilateral spinal dorsal horn.
AB  - Significant decreases in the protein levels of potassium-chloride co-transporter
      2 (KCC2) were detected in the ipsilateral spinal dorsal horn 4h following loose
      ligation of the sciatic nerve. These decreases were associated with a change in
      hindlimb weight distribution suggestive of pain behavior. In contrast, no changes
      in GABA-A receptor subunit alpha-1 levels were detected. The decreases in KCC2
      coincided with a significant ipsilateral increase in BDNF protein levels. Both
      the decreases in KCC2 levels and the early pain behavior were prevented by
      intrathecal pre-treatment with the BDNF-sequestering TrkB/Fc chimera protein or
      the tyrosine kinase blocker K252a. The ligation-associated decreases in KCC2
      levels were transient. In the ipsilateral spinal dorsal horn of ligated animals
      exhibiting weight-bearing pain behavior 7 days after the ligation the KCC2 levels
      were identical to those in control or sham-operated animals. These data suggested
      that TrkB-dependent reduction in KCC2 protein levels in the spinal dorsal horn
      was an early consequence of peripheral nerve injury. This decrease in KCC2 may
      have elicited an early increase in overall dorsal horn neuronal excitability
      perhaps through a loss of GABA inhibition which is critically dependent on KCC2
      activity. The increased neuronal excitability may in turn have caused enhanced
      and exaggerated communication between primary afferents and dorsal horn neurons
      to contribute to the early behavioral signs of pain.

PMID- 18063480
TI  - Interaction between protein kinase D1 and transient receptor potential V1 in
      primary sensory neurons is involved in heat hypersensitivity.
AB  - In previous studies we demonstrated that protein kinase D1 (PKD1/PKCmu) could
      directly phosphorylate the transient receptor potential V1 (TRPV1) at its N
      terminal region and enhance the function of TRPV1 in CHO cells stably transfected
      with TRPV1. In the current study we assessed the involvement of PKD1 in pain
      modulation and explored the possible interaction between PKD1 and TRPV1 in rat
      inflammatory heat hypersensitivity. PKD1 was translocated to cytoplasmic membrane
      fraction and was trans-phosphorylated only in membrane fraction but not in
      cytoplasmic fraction of dorsal root ganglia (DRG) at 2 and 6h after Complete
      Freund's Adjuvant (CFA) treatment. Pre i.t. injection of PKD1 antisense for 4 d
      or post-i.t. injection for 4 d both alleviated CFA-induced thermal
      hypersensitivity. Likewise, overexpression of PKD1 in DRG significantly enhanced,
      while dominant negative PKD1 (DN-PKD1) partly attenuated, heat hypersensitivity.
      Both PKD1 and TRPV1 were translocated to the cytoplasmic membrane in DRG 6 h
      after CFA treatment and, at that time, PKD1 interacted with TRPV1 by co
      immunoprecipitation in DRG. Electrophysiological measurements indicated that DRG
      with overexpression of PKD1 were more sensitive to low dose capsaicin than those
      expressing DN-PKD1. The average magnitude of the peak inward current evoked by
      capsaicin was greater in the DRG overexpressing PKD1 than in those expressing DN
      PKD1. Furthermore, overexpressed PKD1 could up regulate, whereas PKD1 antisense
      could knock down TRPV1 content in DRG through posttranscriptional regulation
      manner. We concluded that PKD1 in DRG, through interaction with TRPV1, is
      involved in developing and maintaining inflammatory heat hypersensitivity.

PMID- 18063481
TI  - Real-time imaging of surface evolution driven by variable-energy ion irradiation.
AB  - We describe the design of a tandem instrument combining a low-energy electron
      microscope (LEEM) and a negative ion accelerator. This instrument provides video
      rate imaging of surface microtopography and the dynamics of its evolution during
      irradiation by energetic ions, at temperatures up to 1700 K. The negative ion
      beam is incident on the sample at normal incidence with impact energies
      selectable in the range 0-5 keV, and with current densities up to 30 muA/cm2 (
      approximately 2 x 10(14)ions/cm2 s or approximately 0.2 ML/s). The LEEM operates
      at a base pressure in the 10(-9)Pa range. We describe the design and operating
      principles of the instrument and present examples of Pt(111) and Si(001) self-ion
      irradiation experiments.

PMID- 18063482
TI  - Acute phase response in mice experimentally infected with Trypanosoma congolense:
      a molecular gauge of parasite-host interaction.
AB  - Mice infected with Trypanosoma congolense developed a severe anaemia 1 week after
      infection, which persisted till treatment with diminazine aceturate when the
      packed cell volume (PCV) recovered to pre-infection levels. This was accompanied
      by a marked increase in the plasma levels of the acute phase proteins (APP),
      serum amyloid P-component (SAP) and haptoglobin (Hp). The initial peak levels of
      Hp and SAP were attained 7 and 12 days post-infection (DPI), respectively.
      Thereafter SAP levels decreased significantly to near pre-infection levels, but
      later increased even after treatment to give a second peak 34 DPI after which
      there was a decline till the study was terminated. The Hp levels on the other
      hand decreased to an intermediate level after the initial peak increasing to a
      second peak 22 DPI. Thereafter Hp decreased significantly following diminazine
      aceturate treatment to reach pre-infection levels within 5 days post-treatment.
      This indicates that T. congolense-infected mice develop severe anaemia
      accompanied by an acute phase response leading to an increase in SAP and Hp but
      that following treatment divergent responses occurred indicating differences in
      the pathways for stimulation of the APP. Haptoglobin was shown to be an earlier
      indicator of infection and a better marker in monitoring the response to
      treatment.

PMID- 18063483
TI  - High prevalence of Cryptosporidium bovis and the deer-like genotype in calves
      compared to mature cows in beef cow-calf operations.
AB  - Recent studies have identified the novel, host adapted Cryptosporidium bovis and
      the deer-like genotype in dairy cattle from farms in the United States, China,
      India and Europe. This novel species and genotype appear to be more prevalent in
      older, post-weaned dairy cattle than previously thought. However, little
      information is available on their prevalence in beef cow-calf operations. In the
      present study, we determined the prevalence of Cryptosporidium species in 98
      calves (6-8 months old) and 114 cows (>2 years old) in seven beef cow-calf herds
      in western North Dakota. DNA was extracted from fecal samples and Cryptosporidium
      spp. were identified by amplification of the 18S rRNA gene followed by sequencing
      or RFLP analysis. All seven herds tested positive for Cryptosporidium. Overall,
      43/212 (20.3%) animals were positive. Only five of these positives were from
      cows. C. bovis, the deer-like genotype and C. andersoni were identified in 9.4,
      6.6 and 1.4% of animals sampled, respectively. C. parvum was not identified in
      any of the positive samples. C. bovis, the deer-like genotype and C. andersoni
      were detected in 6/7, 5/7 and 2/7 herds, respectively. C. bovis and the deer-like
      genotype were primarily detected in calves, while C. andersoni was only detected
      in cows. Six isolates could not be typed. These results show a relatively high
      prevalence of C. bovis and the deer-like genotype in 6-8-month-old beef calves
      compared to cows older than 2 years in the seven herds studied.

PMID- 18063484
TI  - Pharmacologically induced and stimulus evoked rhythmic neuronal oscillatory
      activity in the primary motor cortex in vitro.
AB  - Parkinson's disease (PD) is associated with enhanced synchronization of neuronal
      network activity in the beta (15-30 Hz) frequency band across several nuclei of
      the basal ganglia (BG). Deep brain stimulation of the subthalamic nucleus (STN)
      appears to reduce this pathological oscillation, thereby alleviating PD symptoms.
      However, direct stimulation of primary motor cortex (M1) has recently been shown
      to be effective in reducing symptoms in PD, suggesting a role for cortex in
      patterning pathological rhythms. Here, we examine the properties of M1 network
      oscillations in coronal slices taken from rat brain. Oscillations in the high
      beta frequency range (layer 5, 27.8+/-1.1 Hz, n=6) were elicited by co
      application of the glutamate receptor agonist kainic acid (400 nM) and muscarinic
      receptor agonist carbachol (50 microM). Dual extracellular recordings, local
      application of tetrodotoxin and recordings in M1 micro-sections indicate that the
      activity originates within deep layers V/VI. Beta oscillations were unaffected by
      specific AMPA receptor blockade, abolished by the GABA type A receptor (GABA(A)R)
      antagonist picrotoxin and the gap-junction blocker carbenoxolone, and modulated
      by pentobarbital and zolpidem indicating dependence on networks of GABAergic
      interneurons and electrical coupling. High frequency stimulation (HFS) at 125 Hz
      in superficial layers, designed to mimic transdural/transcranial stimulation,
      generated gamma oscillations in layers II and V (incidence 95%, 69.2+/-7.3 Hz,
      n=17) with very fast oscillatory components (VFO; 100-250 Hz). Stimulation at 4
      Hz, however, preferentially promoted theta activity (incidence 62.5%, 5.1+/-0.6
      Hz, n=15) that effected strong amplitude modulation of ongoing beta activity.
      Stimulation at 20 Hz evoked mixed theta and gamma responses. These data suggest
      that within M1, evoked theta, gamma and fast oscillations may coexist with and in
      some cases modulate pharmacologically induced beta oscillations.

PMID- 18063485
TI  - Bovine lactoferrin protects RSC96 Schwann cells from tumor necrosis factor-alpha
      induced growth arrest via extracellular-signal-regulated kinase 1/2.
AB  - Bovine lactoferrin (bLF) is a member of the transferrin protein family that is
      abundant in bovine milk. Recent studies have shown that bLF plays roles in the
      regulation of cell growth. However, the biological function of bLF in the
      peripheral nervous system is still unclear. In this study, the immortalized rat
      Schwann cells (RSC96) were exposed to bLF at concentrations ranging from 10 to
      800 microg/ml for 48 h and compared with control group. The bromodeoxyuridine
      BrdU cell viability assay was used to examine the effect of bLF on cell viability
      of RSC96 Schwann cells. Cell-counting test was used to assay the growth rate of
      RSC96 cells after exposure to bLF, and immunoblot analysis was used to test the
      signaling pathway controlled by bLF in the RSC96 cells. It was found that the
      viability of the RSC96 cells was increased by more than 25% when treated with 50
      microg/ml bLF and the cell number of RSC96 cells was increased by more than
      threefold when treated with 800 microg/ml bLF. Our results showed that bLF could
      significantly improve viability and number of RSC96 Schwann cells. Also, bLF
      could significantly increase the phosphorylation state of extracellular-signal
      regulated kinase 1/2 (ERK1/2) that could be specifically inhibited by PD98059.
      Furthermore, bLF could not only protect RSC96 cells from tumor necrosis factor
      alpha (TNF-alpha) -induced growth arrest but could also restore proliferation
      rate in TNF-alpha-treated RSC96 cells. In conclusion, bLF plays a crucial role in
      the proliferation of RSC96 Schwann cells and the protection of RSC96 Schwann
      cells from TNF-alpha-induced growth arrest via ERK1/2 protein.

PMID- 18063486
TI  - From menarche to menopause: exploring the underlying biology of depression in
      women experiencing hormonal changes.
AB  - Epidemiologic data consistently report an elevated prevalence of major depressive
      disorder (MDD) in women. This increase begins during adolescence and continues
      through the menopausal transition. Population-based clinical studies report an
      increase in the incidence of MDD during perimenopause compared to either the
      premenopausal or postmenopausal period. Evidence suggests that fluctuations and
      decline of hormonal levels are correlated with this observed increase in risk for
      MDD. A strong predictor of depression in the perimenopausal period is a previous
      history of MDD. However, recent studies revealed an increased risk of new onset
      depression in perimenopausal women without a history of MDD. Additionally, recent
      reports have indicated that the presence of vasomotor symptoms may be associated
      with an increased the risk for MDD. The objective of this paper is to review
      evidence that would support our hypothesis that neurotransmitter systems are
      affected by changes in hormonal status over the course of a woman's life, leading
      to increase vulnerability to perimenopausal depression. Relevant data from
      nonclinical experiments will be discussed in the context of observed clinical
      evidence of the risk for MDD before, during, and after the menopausal transition.
      A testable hypothesis will be proposed to advance our understanding of hormonal
      effects on mood.

PMID- 18063487
TI  - A hypothetical biological synovial fluid for treatment of temporomandibular joint
      disease.
AB  - Temporomandibular Joint disorder (TMD) is a common disorder of mandibular motion
      system with distinct clinicopathological characteristics. TMD may cause to change
      in the components of synovial fluid, that affects the functions on lubrication
      and nutrition of cartilage. Boundary lubrication system contributing to the low
      friction of joint consists of three parts: lubricin, surface-active phospholipids
      and hyaluronan (HA). Diminishment of lubrication function is thereby implicated
      as an adverse contributing factor in degenerative joint diseases such as internal
      derangement, osteoarthrosis. Moreover, mesenchymal stem cells (MSCs) of synovial
      membrane can be obtained without irreversible damage, are easily expandable with
      limited senescence. We postulate that biological active components secreted from
      MSCs are separated and accumulated by gel permeation chromatography, and then we
      use the ultra-flirtation of serum and biologically active components to
      reconstruct the biological synovial fluid in order to rehabilitate the boundary
      lubrication system and the nutrition of cartilage. Further study investigating
      the components of biological synovial fluid provides with new treatment strategy
      for TMD.

PMID- 18063488
TI  - A mycolyl transferase mutant of Rhodococcus equi lacking capsule integrity is
      fully virulent.
AB  - Rhodococcus equi is a mucoid Gram-positive facultative intracellular pathogen
      which can cause severe bronchopneumonia in foals and AIDS patients. A
      polysaccharide capsule which gives R. equi a mucoid appearance has long been
      suspected to be a virulence factor. Here, we describe a transposome mutant in the
      gene fbpA of strain R. equi 103 causing absence of a capsular structure. FbpA is
      a chromosomal gene homologous to antigen 85 (Ag85) mycolyl chain transferase gene
      of Mycobacterium tuberculosis. The mutant multiplied normally in isolated
      macrophages, was able to establish the unusual R. equi-containing vacuole in
      macrophages, was cytotoxic for macrophages, and was virulent in a mouse model.
      Colonies had a dry appearance on nutrient agar and defective capsule structure.
      Surprisingly, fbpA mutants cured of the virulence-associated plasmid were found
      in a phagosome that was more alkaline than that of the corresponding wild-type
      bacteria, were more cytotoxic and even multiplied to some extent. This study
      suggests that the capsule is not an important virulence factor of R. equi and
      that it may even counteract virulence traits.

PMID- 18063489
TI  - Extended spectrum beta-lactamase SHV-12-producing Salmonella from poultry.
AB  - Salmonella strains isolated from poultry and poultry products over the period
      2005-2006 have been investigated in order to ascertain the presence of extended
      spectrum cephalosporins (ESC) resistance. Twelve (ESC)-resistant isolates (n=1 S.
      Enteritidis, n=1 S. Braenderup and n=10 S. Livingstone) were characterized as SHV
      12-positive. The multi-drug resistant S. Livingstone SHV-12-producing isolates,
      untypeable by pulsed-field gel electrophoresis (PFGE), showed a clonal
      relationship by random amplified polymorphic DNA (RAPD) analysis. The SHV-12 beta
      lactamase is reported for the first time in Salmonella enterica strains isolated
      from poultry in Italy. The results suggest poultry as a source of Salmonella
      carrying extended spectrum beta-lactamases (ESBLs) genes and highlights the need
      of monitoring animal productions to prevent spreading of (ESC)-resistant strains.

PMID- 18063490
TI  - Ultra low-dose hormone replacement therapy and bone protection in postmenopausal
      women.
AB  - OBJECTIVES: The aim of the present study was to evaluate the effects of low doses
      of hormone replacement therapy (HRT) in normal young postmenopausal women.
      METHODS: In an open trial healthy, non-obese postmenopausal women received for 2
      years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5 mg
      norethisterone acetate each pill for 28 days, or 0.5 mg of 17beta-estradiol and
      0.25 mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000
      mg of calcium per day. Control group consisted of women receiving only 1000 mg of
      calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green
      climacteric scale for the first 12 weeks of the study while bleeding profiles,
      bone mineral density (BMD) and bone turnover were assessed for 24 months.
      RESULTS: LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical
      symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine
      (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed
      a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck
      (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral
      neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%,
      respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD
      HRT the BMD values were significantly (P<0.05) different from those measured in
      calcium-treated women. CONCLUSIONS: LD-HRT and Ultra-LD-HRT can alleviate
      subjective symptoms providing an effective protection against the postmenopausal
      decrease of BMD.

PMID- 18063491
TI  - Fluoropolymers as low-surface-energy tooth coatings for oral care.
AB  - A range of low-surface-energy fluoropolymers has been synthesised and their
      effectiveness as dental-care coatings for plaque, stain and erosion prevention
      has been evaluated using a series of oral care models employing pressed discs of
      calcium hydroxyapatite or sections of human teeth. Since the blocking of dentinal
      tubules is a key mechanistic strategy in the treatment of dentine
      hypersensitivity, the capability of these non-permanent fluoropolymer coatings to
      occlude the pore structure of human dentine and to reduce the outward flow of
      simulated dentinal fluid has also been investigated. Several of the fluoropolymer
      coatings have been found to inhibit bacterial adhesion but no correlation has
      been established between anti-adhesion efficacy and fluorine content or surface
      energy. All the fluoropolymers have been seen to reduce stain uptake by pellicle
      coated HA discs, with homopolymers being considerably more effective than
      copolymers. Some fluoropolymer coatings have also been shown to inhibit the acid
      demineralisation of hydroxyapatite discs and to reduce dentine permeability.
      Coatings of the 2:1 copolymer of 1H,1H,2H,2H-perfluorodecyl acrylate and 2
      hydroxyethyl acrylate are most promising, exhibiting significant anti-adhesion
      and anti-erosion efficacy and reducing dentine permeability to a level that is
      comparable with that achieved with the standard treatment employed in commercial
      anti-sensitivity formulations.

PMID- 18063492
TI  - Simulated neonatal exposure to DEHP and MEHP from PVC enteral nutrition products.
AB  - The leaching of di(2-ethylhexyl)phthalate (DEHP) and mono(2-ethylhexyl)phthalate
      (MEHP) from medical products made of polyvinyl-chloride (PVC) to enteral
      nutrition (EN) for neonatal patients was determined in a simulated study. The
      study simulated a typical case of EN administration to a neonatal patient (body
      weight, 3 kg) in a neonatal care unit (temperature, 25 degrees C); the medical
      products used were an irrigator and catheter containing DEHP (9.1-31.8%, w/w) as
      a plasticizer. The worst-case daily exposures of the neonatal patient to DEHP and
      MEHP by the administration of EN were estimated to be 148 and 3.72 microg/(kg
      day), respectively, as assessed from the levels of these compounds leaching from
      the medical products to the EN. The use of DEHP-free medical products reduced the
      exposure of DEHP and MEHP to the minimum levels contained in the EN at
      preparation. A transition to DEHP-free medical products for neonatal patients
      would be effective in reducing the exposure of neonatal patients to DEHP via EN
      administration.

PMID- 18063493
TI  - Sulfated and non-sulfated amphiphilic-beta-cyclodextrins: impact of their
      structural properties on the physicochemical properties of nanoparticles.
AB  - PURPOSE: The aim of this work was to study the preparation of nanospheres from
      amphiphilic beta-cyclodextrins formed (a) by different acylation degrees (DA) at
      the secondary hydroxyl face (DA=14 and 21) followed by varying (b) the
      sulfatation degrees (DS) at the primary hydroxyl face (DS=0, 4 and 7). METHODS:
      The physicochemical properties of the synthesized compounds such as molecular
      weights, the theoretical HLB values and the critical micellar concentration
      values and their surface area were presented. The nanoparticles prepared from
      amphiphilic beta-cyclodextrins were characterized by mean size, zeta potential
      and their morphology. RESULTS: The compounds presented hydrophile-lipophile
      balance values ranging from 5.6 to 10. For sulfated amphiphilic beta
      cyclodextrins having HLB values higher than 8, were able to self-organize in
      water to form nanoparticles. However, for the amphiphilic beta-cyclodextrins that
      HLB values lower than 6.6 are insoluble in water but soluble in organic solvents
      rendering possible the preparation of nanoparticles by nanoprecipitation
      technique. CONCLUSION: An interesting correlation between the amphiphilic-beta
      cyclodextrin structures and their ability to form nanospheres has been
      established. The association of sulfated amphiphilic-beta-CDs to the peracylated
      amphiphilic-beta-CDs was interesting, it led to improve the stability of
      nanospheres size and probably confer them a biological activity.

PMID- 18063494
TI  - Aqueous crude extract of Rhoeo discolor, a Mexican medicinal plant, decreases the
      formation of liver preneoplastic foci in rats.
AB  - There are many plants in Mexico with medicinal properties, some of them used in
      alternative medicine to treat cancer, such is the case of Rhoeo discolor L. Her
      Hance (Commelinaceae family); however, there are not scientific reports that
      validate their antitumoral property. The present study shows the protective
      effects of the Rhoeo discolor aqueous crude extract (ACE) against rat liver
      cancer using the resistant-hepatocyte model. The carcinogenesis protocol
      consisted on the initiation with N-diethylnitrosamine, followed by the promotion
      with 2-acetylaminofluorene and a partial hepatectomy. After 24 days, the gamma
      glutamyl transpeptidase positive, corresponding to altered hepatocytes foci
      (AHF), were quantified. Additionally to discard a possible carcinogenic effect of
      ACE, it was first tested as promoting agent instead 2-acetylaminofluorene, and
      second, ACE was administered as initiator and promoter instead of the whole
      carcinogenic treatment. In summary, firstly, ACE administration reduced the
      number and area of preneoplastic lesions with dose below 20mg/kg body weight and
      secondly, ACE administration neither presented a promoting or initiator effects
      nor induced the development of AHF. Results of this investigation justify
      continuing with further studies of Rhoeo discolor components to develop
      chemoprevention strategies as an option in the treatment of cancer.

PMID- 18063495
TI  - The effects of Morinda citrifolia L. (noni) on the immune system: its molecular
      mechanisms of action.
AB  - The aim of this study was to investigate the mechanisms involved in the
      immunomodulatory effects of Morinda citrifolia L. (noni) in vitro and in vivo in
      mice. In vitro, Tahitian Noni Juice (TNJ) and Noni fruit juice concentrates
      (NFJC) (1, 5mg/mL) potently activate cannabinoid 2 (CB2), but inhibit cannabinoid
      1 (CB1) receptors in a concentration-dependant manner. In vivo, oral
      administration of TNJ ad libitum for 16 days decreased the production of IL-4,
      but increased the production of IFN-gamma. These results suggest that noni
      modulates the immune system via activating of the CB2 receptors, and suppressing
      of the IL-4, but increasing the production of IFN-gamma cytokines. It may also
      exert beneficial immunomodulation effects in conditions involving inadequate
      immune responses.

PMID- 18063496
TI  - Antidiabetic activity of Vatairea macrocarpa extract in rats.
AB  - In the present paper the anti-diabetic effects of stem-bark extract (ethanol 70%)
      of Vatairea macrocarpa, a traditional diabetes mellitus treatment widely used in
      Brazil, are reported. The extract was administered orally at a dose of 250 or 500
      mg/kg, for 22 days, to normal and streptozotocin-diabetic rats. In extract
      treated (500 mg/kg) diabetic rats serum and urinary glucose, urinary urea, food
      and fluid intake were decreased, while body weight gain was increased, all of
      which indicate an improvement in diabetic state (p<0.05). No effects of the
      extract were observed in non-diabetic rats. In extract treated (500 mg/kg)
      diabetic group HOMA-R (homeostasis model for assessment of insulin resistance)
      was lower at the end of 22 days, as compared to diabetic non treated control
      group. Insulin was the reference substance used in the experiments. In an oral
      glucose tolerance test, the time to reach maximal glycemia was greater in
      diabetic 500 mg/kg treated group than in control group. These anti-diabetic
      effects could be related to an improved insulin resistance, although a possible
      effect on pancreatic B-cell function cannot be excluded. Thus, our data of sub
      chronic experiments suggest that long-term use of V. macrocarpa stem-bark extract
      may be helpful in treating diabetic conditions.

PMID- 18063498
TI  - The coming out of the brain mineralocorticoid receptor.
AB  - Corticosteroids - secreted after stress - have profound effects on brain and
      behavior. These effects are mediated by mineralocorticoid and glucocorticoid
      receptors, which are abundantly expressed in limbic neurons. The role of
      mineralocorticoid receptors in higher brain functions has never been well
      understood. Here we argue that the recently discovered low-affinity membrane
      version of the mineralocorticoid receptor contributes to the initial phase of the
      stress reaction; this is complemented by the glucocorticoid receptor which
      terminates the stress response. This concept may explain why human carriers of a
      mineralocorticoid receptor gene variant display enhanced neuroendocrine and
      autonomic responsiveness to a psychological stressor.

PMID- 18063497
TI  - A 'GAG' reflex prevents repair of the damaged CNS.
AB  - The extracellular matrix of the central nervous system (CNS) serves as both a
      supporting structure for cells and a rich source of signaling molecules that can
      influence cell proliferation, survival, migration and differentiation. A large
      proportion of this matrix is composed of proteoglycans--proteins with long chains
      of polysaccharides, called glycosaminoglycans (GAGs), covalently attached.
      Although many of the activities of proteoglycans depend on their core proteins,
      GAGs themselves can influence cell signaling. Here we review accumulating
      evidence that two GAGs, chondroitin sulfate and hyaluronan, play essential roles
      during nervous system development but also accumulate in chronic CNS lesions and
      inhibit axonal regeneration and remyelination, making them significant hindrances
      to CNS repair. We propose that the balance between the synthesis and degradation
      of these molecules dictates, in part, how regeneration and recovery from CNS
      damage occurs.

PMID- 18063499
TI  - Intermediate syndrome following organophosphate insecticide poisoning.
AB  - Acute organophosphate insecticide poisoning can manifest 3 different phases of
      toxic effects, namely, acute cholinergic crisis, intermediate syndrome (IMS), and
      delayed neuropathy. Among them, IMS has been considered as a major contributing
      factor of organophosphate-related morbidity and mortality because of its frequent
      occurrence and probable consequence of respiratory failure. Despite a high
      incidence, the pathophysiology that underlies IMS remains unclear. Previously
      proposed mechanisms of IMS include different susceptibility of various
      cholinergic receptors, muscle necrosis, prolonged acetylcholinesterase
      inhibition, inadequate oxime therapy, downregulation or desensitization of
      postsynaptic acetylcholine receptors, failure of postsynaptic acetylcholine
      release, and oxidative stress-related myopathy. The clinical manifestations of
      IMS typically occur within 24 to 96 hours, affecting conscious patients without
      cholinergic signs, and involve the muscles of respiration, proximal limb muscles,
      neck flexors, and muscles innervated by motor cranial nerves. With appropriate
      therapy that commonly includes artificial respiration, complete recovery develops
      5-18 days later. Patients with atypical manifestations of IMS, especially a
      relapse or a continuum of acute cholinergic crisis, however, were frequently
      reported in clinical studies of IMS. The treatment of IMS is mainly supportive.
      Nevertheless, because IMS generally concurs with severe organophosphate toxicity
      and persistent inhibition of acetylcholinesterase, early aggressive
      decontamination, appropriate antidotal therapy, and prompt institution of
      ventilatory support should be helpful in ameliorating the magnitude and/or the
      incidence of IMS. Although IMS is well recognized as a disorder of neuromuscular
      junctions, its exact etiology, incidence, and risk factors are not clearly
      defined because existing studies are largely small-scale case series and do not
      employ a consistent and rigorous definition of IMS. Without a clear understanding
      of the pathophysiology of IMS, specific therapy is not available. The prognosis
      of IMS, however, is likely to be favorable if respiratory failure can be promptly
      recognized and treated accordingly.

PMID- 18063500
TI  - Effect of glyburide-metformin combination tablet in patients with type 2
      diabetes.
AB  - BACKGROUND: To evaluate the efficacy and safety of glyburide/metformin combined
      tablet compared to glyburide or metformin alone in patients with type 2 diabetes.
      METHODS: In this 16-week, multicenter, randomized, double-blind, 4-arm and
      parallel clinical trial study, 100 patients with type 2 diabetes mellitus were
      recruited and 76 patients were available for statistical analysis at the end of
      the study. After 1 week of placebo washout period, eligible patients were
      randomly assigned into 1 of 4 treatment groups: glyburide 5 mg b.i.d.; metformin
      500 mg b.i.d.; glyburide/metformin 2.5 mg/500 mg b.i.d.; or glyburide/metformin
      5.0 mg/500 mg b.i.d. The doses were titrated every 2 weeks to a maximum of 4
      tablets per day if the patients fasting plasma glucose (FPG) still exceeded 140
      mg/dL. Efficacy was evaluated by the changes from baseline in glycosylated
      hemoglobin (HbA1c) and FPG at week 16. Adverse events were recorded and
      summarized by treatment group. RESULTS: At week 16, patients who received
      glyburide/metformin 2.5 mg/500 mg or 5.0 mg/500 mg tablets had greater reductions
      in FPG (all p<0.001) compared with glyburide or metformin monotherapy. Patients
      who took glyburide/ metformin 2.5 mg/500 mg tablet and glyburide/metformin 5.0
      mg/500 mg tablet had significant decreases in HbA1c (both p<0.0125). Furthermore,
      treatment with glyburide/metformin 2.5 mg/500 mg resulted in significantly
      greater reduction in HbA1c compared to glyburide or metformin (-1.77%, p<0.001
      and -1.34%, p=0.002), and treatment with glyburide/metformin 5.0 mg/500 mg
      resulted in significant lowering of HbA1c compared to glyburide or metformin
      alone (-1.73%, p<0.001 and -1.30%, p=0.005). Both the glyburide/metformin 2.5
      mg/500 mg and glyburide/metformin 5.0 mg/500 mg combination therapy groups
      experienced fewer gastrointestinal adverse events than the metformin monotherapy
      group. CONCLUSION: Both glyburide/metformin 2.5 mg/500 mg and glyburide/metformin
      5.0 mg/500 mg combination therapy were efficacious and well tolerated in the
      treatment of Chinese patients with type 2 diabetes mellitus.

PMID- 18063501
TI  - Complications of pure transperitoneal laparoscopic surgery in urology: the Taipei
      Veterans General Hospital experience.
AB  - BACKGROUND: We present our experience of complications of pure transperitoneal
      laparoscopic surgery in urology at Taipei Veterans General Hospital. METHODS:
      Between September 2003 and March 2006, 185 laparoscopic urologic operations were
      performed, consisting of 70 nephrectomies (36 radical, 17 partial, 11 simple, 6
      donor), 28 adrenalectomies, 28 nephroureterectomies, 22 radical prostatectomies,
      17 ureterolithotomies, 6 radical cystectomies, 5 pyeloplasties, 2 renal cyst
      unroofings, 2 nephropexies and 5 other operations. We reviewed the database of
      the patients to evaluate the complications and analyze factors related to
      laparoscopic surgeries. RESULTS: A total of 25 patients had 26 complications
      (14.1%, major in 4, minor in 22). The complications were categorized into
      intraoperative and postoperative complications in 10 and 16 patients,
      respectively. The mortality rate was 0%. The conversion rate was 0.54% (1
      patient). The re-operation rate was 1.08% (2 patients). The most common
      intraoperative complication was vascular injury (5 patients). The incidence of
      complication was related to the difficulty level of operation. No statistically
      significant differences were found between complication rate and patient age,
      patient body mass index or the American Society of Anesthesiologist score.
      CONCLUSION: The complications of laparoscopic urologic surgeries are strongly
      correlated with the operative difficulties. In spite of elevated complication
      rates in difficult surgeries, the major complication rate in this study was very
      low. As the laparoscopic surgeries in urology involve more and more technique
      dependent difficult fields, documentation and analysis of experience of
      complications is important for the development of this surgical modality.

PMID- 18063502
TI  - Prevalence and clinical characteristics of simple renal cyst.
AB  - BACKGROUND: We investigated simple renal cysts to understand the prevalence in
      healthy individuals and evaluate their clinical characteristics to determine
      whether or not there are any risk factors associated with simple renal cysts.
      METHODS: Abdominal sonography was performed in 577 individuals (317 men, 260
      women; mean age, 48.84 years; age range, 20-94 years) who received health check
      up in January to February 2005. Data including age, sex, renal sonographic
      findings (cyst number, site, diameter, renal stones), values of serum
      cholesterol, glucose and creatinine, urine analysis (proteinuria, hematuria,
      pyuria), and smoking habit were analyzed. RESULTS: The overall prevalence of
      simple renal cysts was 10.7%, ranging from 2.38% in the 2nd to 35.29% in the 7th
      or later decade of life. The prevalence increased with age (p<0.001). The mean
      age of individuals with cysts was significantly older than those without cysts
      (57.65+/-13.35 vs. 47.78+/-12.40 years; p<0.001). Male-to-female ratio was 2.81
      (15.14% vs. 5.38%; p<0.001). The majority of cysts were solitary (82.3%). Mean
      largest diameter of cysts was 20.89+/-12.62 mm. The mean size of cysts in every
      age group was not statistically different. Factors significantly associated with
      simple renal cysts were age (odds ratio [OR], 4.37; p<0.001), sex (OR, 0.32;
      p<0.001), serum creatinine (OR, 11.77; p=0.001), proteinuria (OR, 3.11; p=0.004),
      renal stone (OR, 2.47; p=0.006), and smoking (OR, 2.80; p<0.001). However, in
      multivariate analysis, except proteinuria, all of the above factors were
      significantly related to the occurrence of simple renal cysts. CONCLUSION: The
      overall prevalence of simple renal cysts in healthy individuals was 10.7%. Age,
      sex, renal stone, serum creatinine, and smoking were found to be risk factors for
      the presence of simple renal cysts.

PMID- 18063503
TI  - Uveitis with biopsy-proven sarcoidosis in Chinese--a study of 60 patients in a
      uveitis clinic over a period of 20 years.
AB  - BACKGROUND: The aim of this study was to assess the clinical features of uveitis
      with biopsy-proven sarcoidosis in Chinese patients. METHODS: This was a
      retrospective study of uveitis patients with biopsy-proven sarcoidosis who
      consecutively visited the uveitis clinic of Taipei Veterans General Hospital from
      1986 to 2005. Medical records were reviewed to obtain demographic data, initial
      symptoms, biopsy sites, pulmonary conditions detected by chest X-ray and
      manifestations of uveitis. From 2002 onwards, patients also received chest
      computed tomography (CT). RESULTS: A total of 60 uveitis patients with biopsy
      proven sarcoidosis were identified. Forty-four patients (73%) were found in the
      last 4 years. Female predominance with a male-to-female ratio of 1:6.5 was found.
      The most common initial symptom was uveitis in 41 patients (68%). The most common
      positive biopsy sites were mediastinal lymph nodes, lung, conjunctiva and skin.
      Twenty (90.9%) of 22 patients with chest X-ray stage 0 showed >or= stage 1 on CT.
      The mean age at uveitis onset was 47.7+/-14.7 years (range, 21-76 years), with no
      gender difference (p=0.913). A peak incidence was found in the 6th decade of
      life. There was bilateral eye involvement in 54 patients (90%). Frequency of the
      manifestations of uveitis showed isolated anterior uveitis in 2 patients (3.3%),
      isolated posterior uveitis in 8 patients (13.3%), intermediate and posterior
      uveitis (i.e. anterior uveitis sparing) in 16 patients (26.7%), and panuveitis in
      34 patients (56.7%). CONCLUSION: A marked increase was noted since 2002. One of
      the causes is the performance of chest CT. Chest CT is useful to discover
      mediastinal lymphadenopathy and other lesions suggestive of sarcoidosis, as well
      as to help guide tissue confirmation in patients with peculiar uveitis features
      indicative of sarcoidosis. Female predominance and peak incidence of uveitis
      onset in the 6th decade of life were found. The posterior segment was the most
      common localization of uveitis in biopsy-proven sarcoidosis in Chinese.

PMID- 18063504
TI  - Application of in vivo stain of methylene blue as a diagnostic aid in the early
      detection and screening of oral squamous cell carcinoma and precancer lesions.
AB  - BACKGROUND: Early detection of oral malignant or precancerous lesion by screening
      individuals with high-risk factors may identify candidates who should receive
      treatment to prevent cancer progression and reduce patient mortality. Among the
      diagnostic tools, in vivo staining is advocated as a simple, inexpensive, and
      fairly sensitive method. METHODS: The present study involved the examination of
      58 patients suspected of having oral malignant or precancerous lesions by
      methylene blue staining. The results of methylene blue uptake were compared with
      a simultaneous biopsy of these lesions. The pathologically confirmed precancers
      and cancers were the positive targets of this screening, while benign epithelial
      lesions were sorted as negative subjects of screening. RESULTS: The results
      revealed sensitivity of 90%, specificity of 69%, positive predictive value of
      74%, and negative predictive value of 87%. CONCLUSION: We consider that methylene
      blue staining is a useful diagnostic adjunct in a large, community-based oral
      cancer screening program for high-risk individuals.

PMID- 18063505
TI  - Dermatitis herpetiformis and vitiligo.
AB  - Dermatitis herpetiformis (DH) is a rare immunobullous disorder of the skin that
      is associated with gluten hypersensitivity. Subepidermal IgA-type antibody
      deposition against tissue transglutaminase leads to dense neutrophilic
      microabscess and eventually into vesicles in dermal papillae, which may
      occasionally merge into bullae. Being a subepidermal vesiculobullous disorder, DH
      is frequently associated with postinflammatory pigmentary changes, particularly
      hypopigmentation. However, the association of DH with true vitiligo is extremely
      rare. Here, we report a 21-year-old male with vitiligo and comorbid DH, and
      review the literature. This new case had severely pruritic, papular and
      papulovesicular lesions that were localized symmetrically and partly confined to
      the pre-existing vitiliginous areas. The skin biopsy specimen taken from an
      erythematous papule on the elbow showed characteristic findings of DH and
      vitiligo. Direct immunofluorescence microscopy of the perilesional skin revealed
      granular IgA deposition of dermal papillae. There are only 10 reports in the
      literature of DH and vitiligo comorbidity.

PMID- 18063506
TI  - Suspected malignant hyperthermia during sevoflurane anesthesia.
AB  - Malignant hyperthermia is a rare anesthetic-related disorder. We present a case
      with unusual presentation. A boy aged 3 years and 9 months who was scheduled for
      Hotz's operation presented normally before the operation. Anesthesia was induced
      by atropine, thiopental and sevoflurane. Trachea intubation was facilitated by
      succinylcholine. Jaw stiffness was first noted although trachea was intubated
      without difficulty. The following tachycardia, hypercapnia and hyperthermia led
      to the diagnosis of malignant hyperthermia. Symptoms were relieved dramatically
      after the discontinuation of sevoflurane. Molecular genetic testing identified a
      novel ryanodine receptor (RYR1) mutation in exon 39, which confirmed malignant
      hyperthermia susceptibility in this patient.

PMID- 18063507
TI  - Gossypiboma--retained surgical sponge.
AB  - Intra-abdominal retained surgical sponge is an uncommon surgical error. Herein,
      we report a 92-year-old woman who was brought to the emergency room for acute
      urinary retention. She had a history of vaginal hysterectomy for uterine prolapse
      18 years previously, performed at our hospital. Retained surgical sponge in the
      pelvic cavity was suspected by abdominal computed tomography. The surgical gauze
      was removed by laparotomy excision and the final diagnosis was gossypiboma.

PMID- 18063508
TI  - Ultrasound and magnetic resonance images of endodermal sinus tumor.
AB  - Endodermal sinus tumor, also known as yolk sac tumor, is a rare malignant ovarian
      tumor that usually occurs in the second decade of life. Here, we report a case of
      endodermal sinus tumor which occurred in a 14-year-old girl. She presented with
      lower abdominal pain for about 4 months. Initial ultrasound findings revealed a
      large ovarian multilocular solid tumor. Doppler study revealed multiple arteriole
      vessels running in the solid section of the tumor from which the lowest
      resistance index of 0.30 was recorded. The lactate dehydrogenase level was 261
      U/L, and alpha-fetoprotein marker was 131,630 ng/mL. Axial contrast-enhanced T1
      weighted magnetic resonance imaging showed a large cystic mass with solid
      components in the peripheral portions of the mass. The peripheral solid portions
      showed strong enhancement, indicating their hypervascularity. She received
      staging operation for malignant ovarian tumor, and the pathology reports revealed
      ovarian malignance of endodermal sinus tumor with omental invasion, stage IIIc.
      This case report suggests that in an adolescent female with elevated alpha
      fetoprotein, low resistance index in the tumor mass and hypervascularity on
      contrast-enhanced T1-weighted magnetic resonance image, the probability of an
      endodermal sinus tumor should be highly suspected preoperatively.

PMID- 18063509
TI  - Delayed return-to-work in workers after non-severe occupational upper extremity
      fracture in Taiwan.
AB  - BACKGROUND/PURPOSE: Occupational injury of the upper extremities account for 24%
      of occupational injuries in Taiwan. However, studies on the timing and factors
      influencing return-to-work are lacking. METHODS: A total of 102 hospitalized
      workers with non-severe upper extremity fractures, defined as without avulsion,
      amputation and nerve damage, were interviewed over the telephone using a
      structured questionnaire at 45, 90 and 180 days after injury. RESULTS: After
      controlling other factors, cases with other-than-digit fracture presented three
      fold more difficulty than those with digit fracture on returning to work (OR,
      0.32; 95% CI, 0.17-0.63). Male workers (OR, 2.70; 95% CI, 1.16-6.25) and those
      with financial help from their employer (OR, 2.32; 95% CI, 1.17-4.60) found it
      easier to return to work 90 days after injury. There were 32% who were still
      unable to return to work 180 days after injury. CONCLUSION: Women workers and
      workers without financial help from employers are at a disadvantage with regard
      to early return-to-work. Other assistance besides medical treatment could be of
      significant help but should be cautiously exercised in extrapolating to workers
      who are not the main breadwinner in their household.

PMID- 18063510
TI  - Chromosomal gain of 3q and loss of 11q often associated with nodal metastasis in
      early stage cervical squamous cell carcinoma.
AB  - BACKGROUND/PURPOSE: Cervical cancer remains a health problem among women
      worldwide. Delineation of genetic changes is critical to understanding the
      molecular basis of tumor progression, as well as for identifying genetic markers
      for early identification of patients at high risk for a poor outcome. METHODS: To
      provide comparative genomic hybridization data for cervical squamous cell
      carcinoma in Taiwan, and to gain further insight into genetic markers associated
      with lymph node metastasis of this disease, we performed comparative genomic
      hybridization analysis of 30 consecutive cases of cervical squamous cell
      carcinoma (24 stage IB and 6 stage IIB). RESULTS: The results disclosed that
      higher staged tumors or those with lymph node metastasis had more chromosomal
      imbalances. The commonly recurrent chromosomal imbalances were gains of 3q
      (46.7%), 1q (36.7%) and 8q (20.0%) and losses of 11q (36.7%), 3p (33.3%), 6q
      (23.3%), and 2q (20.0%). The frequencies of these chromosomal imbalances in stage
      IB and IIB tumors did not differ significantly. However, when compared with
      tumors without lymph node metastasis, the loss of 11q14-q22 (5/9 vs. 3/21, p =
      0.019) and gains of 3q11-q22 and 3q26-qter (6/9 vs. 5/21, p = 0.026) were
      significantly more prevalent in tumors with lymph node metastasis. CONCLUSION:
      The results suggest that certain tumor-associated genes residing on 3q and 11q
      warrant further investigation to elucidate their role in the progression of this
      disease.

PMID- 18063511
TI  - Predictors of treatment response and length of stay for inpatients with major
      depression.
AB  - BACKGROUND/PURPOSE: Depressive illness is highly recurrent, frequently chronic
      and associated with a high level of functional disability. Studies have shown
      that depression combined with anxiety is the most common reason for admission
      worldwide. This study aimed to examine the variables associated with treatment
      response or length of stay (LOS) among a group of inpatients with major
      depression. METHODS: The attending psychiatrist rated severity of depression
      (using the Hamilton Rating Scale for Depression, HAM-D) of the patients (n = 67),
      and the patients were asked to complete several self-rating scales (including the
      Beck Depression Inventory, BDI) on admission. Three days before discharge, these
      assessments were repeated. Logistic regression models were used to examine the
      variables of remission status (defined by the HAM-D or the BDI) and LOS
      (dichotomized by a median of 25 days), respectively. RESULTS: The remission rates
      of depression at discharge defined by the HAM-D (</= 7) and the BDI (</= 8) were
      40% and 16%, respectively. Lower socioeconomic status and less clinical severity
      at admission were associated with clinicians' objective assessment of remission,
      while suicide attempt during this index episode was associated with patients'
      subjective remission. LOS of depressive inpatients was neither related to
      baseline severity nor to remission status at discharge. Patients with positive
      family history and more frequent hospitalization were associated with a hospital
      stay of longer than 25 days. CONCLUSION: There was no evidence to show that
      patients with a long hospital stay would gain treatment benefits over patients
      with short stay. This study provides evidence to support that a structured
      inpatient treatment plan might gain some economic benefits without compromising
      treatment efficacy. The admission of hospitalization repeaters should be managed
      optimally based on the considerations of treatment efficacy and its impact on
      longer hospital stay.

PMID- 18063512
TI  - CT-guided hook wire localization of subpleural lung lesions for video-assisted
      thoracoscopic surgery (VATS).
AB  - BACKGROUND/PURPOSE: Histologic diagnosis of suspicious small subpleural lung
      lesions is difficult and often impossible using existing image-guided needle
      biopsy techniques including video-assisted thoracoscopic wedge resection.
      Preoperative lung lesion localization provides a more obvious target to
      facilitate intraoperative resection. This study reviewed the indications, results
      and complications of CT-guided hook wire localization for subpleural lung lesions
      in video-assisted thoracoscopic surgery (VATS). METHODS: Between February 2001
      and January 2007, 41 patients (20 males, 21 females; mean age, 52.5 +/- 5.1
      years) with 43 subpleural pulmonary lesions underwent preoperative CT-guided
      double-thorn hook wire localization prior to video-assisted thoracoscopic wedge
      resection. Nodule diameters ranged from 2 mm to 26 mm (mean, 9.7 +/- 1.6 mm). The
      distance of the lung lesions from the nearest pleural surfaces ranged from 2 mm
      to 30 mm (mean, 9.6 +/- 2.0 mm). Patients then received VATS within 5 hours. The
      efficacy of preoperative localization was evaluated in terms of procedure time,
      VATS success rate and associated complications of localization. RESULTS: Forty
      three wedge resections of the lungs containing 43 subpleural lung lesions as
      guided or assisted by the inserted hook wires were successfully performed in 41
      VATS procedures (41 of 43 procedures, 95.3%). The mean procedure time for
      preoperative CT-guided hook wire localization was 30.4 +/- 2.8 minutes. Eight
      patients had asymptomatic minimal pneumothoraces (18.6%); six patients had
      minimal needle tract parenchymal hemorrhages (13.9%) and one patient (2.3%) had
      an estimated 100 mL of hemothorax due to a small intercostal artery bleed that
      was cauterized during operation. The mean procedure time for VATS was 103 +/- 9.7
      minutes (range, 44-198 minutes). Pathologic examination revealed seven primary
      lung cancers, 11 metastases, one hemangioma, 19 definite non-neoplastic
      pathologies, two nonspecific chronic inflammation, and three metallic foreign
      bodies. Diagnostic yield was 95%. No major complications related to the
      preoperative hook wire localization and VATS were noted. CONCLUSION: CT-guided
      hook wire fixation is useful, helps in precise lesion localization in VATS wedge
      resection, and has a low rate of minor complications.

PMID- 18063513
TI  - Circulating levels of markers of inflammation and endothelial activation are
      increased in men with chronic spinal cord injury.
AB  - BACKGROUND/PURPOSE: Accelerated atherogenesis is often seen in individuals with
      chronic spinal cord injury (SCI). However, the mechanisms contributing to this
      phenomenon remain unclear. This study aimed to evaluate whether SCI per se is
      associated with a low-grade chronic inflammatory state and endothelial
      activation, both of which are well-documented prerequisites for atherogenesis.
      METHODS: Serum levels of markers of inflammation (C-reactive protein [CRP],
      interleukin-6, and soluble CD40 ligand) and endothelial activation (endothelin-1,
      soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion
      molecule-1 [sVCAM-1]) were measured in SCI patients with CRP levels < 10 mg/L and
      with no evidence of active infection. Sixty-two men with traumatic neurologically
      complete SCI (20 tetraplegics and 42 paraplegics) and 29 age-matched male
      controls were enrolled. RESULTS: Compared with able-bodied controls, subjects
      with SCI had a significantly lower body mass index (BMI) (-7%) and significantly
      lower serum levels of albumin (-10%), creatinine (-20%), low-density lipoprotein
      cholesterol (-10%), and high-density lipoprotein (HDL) cholesterol (-25%), and
      showed a trend toward higher fasting insulin levels. Irrespective of injury level
      and duration, subjects with SCI had significantly higher serum levels, compared
      to able-bodied controls, of CRP (mean, 4.0 +/- 2.7 mg/L vs. 1.4 +/- 1.1 mg/L),
      interleukin-6 (median, 2.5 pg/mL vs. 0.4 pg/mL; range, 1.5-3.6 pg/mL vs. 0.2-0.5
      pg/mL), endothelin-1 (mean, 1.3 +/- 0.4 pg/mL vs. 0.9 +/- 0.3 pg/mL), and sVCAM-1
      (mean, 1170 +/- 318 ng/mL vs. 542 +/- 318 ng/mL). The serum levels of all four
      factors correlated negatively with levels of serum albumin, creatinine and HDL
      cholesterol, but not with BMI or fasting insulin levels. In multivariate
      analyses, SCI was the only factor that was independently associated with
      increased serum levels of CRP, interleukin-6, endothelin-1 and sVCAM-1 after
      adjustment for confounding factors such as serum albumin and creatinine levels
      and parameters of dyslipidemia and insulin resistance. CONCLUSION: In this study,
      we have, for the first time, demonstrated that SCI per se is associated with a
      low-grade chronic inflammatory state and endothelial activation, which may partly
      explain the increased atherogenic risk in patients with long-standing SCI.

PMID- 18063514
TI  - Major complications and associated risk factors of transrectal ultrasound guided
      prostate needle biopsy: a retrospective study of 1875 cases in taiwan.
AB  - BACKGROUND/PURPOSE: Complications from transrectal ultrasound (TRUS) guided
      prostate needle biopsy are occasionally encountered in the daily practice of
      urologists. We tried to determine the associated risk factors of patients who
      suffered from major complications that required hospitalization after TRUS guided
      prostate needle biopsies. METHODS: We did a retrospective review of 1875 TRUS
      guided prostate biopsies performed between January 2002 and December 2005. We
      defined major complications as patients with complications that needed
      hospitalization. We analyzed the association between biopsy complications and
      suspected factors, including age, prostate volume, patients underlying disease,
      selection of prophylactic antibiotics, biopsy core numbers (6, 12, and 15 cores),
      and antiplatelet/anticoagulant usage. RESULTS: There were 124 patients (6.6%)
      with major complication. These major complications were categorized as acute
      prostatitis (3.8%), acute urinary retention (2.1%), hematuria (1.9%), rectal
      bleeding (0.2%), epididymitis (0.2%), sepsis (0.05%), and vasovagal syncope
      (0.05%). Patients with larger prostate size were noted to have higher risk of
      developing transient acute prostatitis and acute urinary retention after prostate
      biopsy. In contrast, age, prophylactic antibiotics (levofloxacin and pipemidic
      acid), underlying diseases (diabetic mellitus, hypertension, hyperlipidemia,
      cerebrovascular accident, coronary artery disease), increased biopsy core
      numbers, and antiplatelet/anticoagulant usage were not associated with major
      complications after prostate biopsy. CONCLUSION: TRUS guided prostate needle
      biopsy is a safe diagnostic tool in most elderly males with or without systemic
      underlying disease.

PMID- 18063515
TI  - Impact of glycemic control, disease duration, and exercise on heart rate
      variability in children with type 1 diabetes mellitus.
AB  - BACKGROUND/PURPOSE: Type 1 diabetes is commonly associated with autonomic
      neuropathy. The present study investigated the influences of glycemic control,
      disease duration (DD), and exercise on autonomic nervous function in children
      with type 1 diabetes by analysis of their heart rate variability (HRV). METHODS:
      Seventy-nine type 1 diabetic children were recruited and categorized into four
      groups by HbA1c of 8% and DD of 4.5 years. HRV parameters as determined by
      separate frequency domain components (low frequency: LnLF, 0.04-0.15 Hz; high
      frequency: LnHF, 0.15-0.5 Hz; total power: LnTP, 0.04-0.5 Hz) were measured both
      at rest and during exercise. Pearson's correlation, one-way ANOVA, and multiple
      regressions with stepwise method were used for statistical analysis. RESULTS:
      While at rest, HbA1c and DD were negatively correlated with all HRV parameters.
      Both HbA1c and DD were significant predictors in LnTP. However, only HbA1c was a
      significant predictor in LnLF and LnHF. Type 1 diabetes patients with HbA1c > 8%
      and DD > 4.5 years had a significantly lower HRV than the other patients. During
      exercise, HRV reduced significantly and no significant correlation between HbA1c
      and HRV or between DD and HRV was observed. Also, a significant difference in HRV
      among the four groups was not demonstrated. The smallest decrement in HRV from
      resting to exercise were in subjects with HbA1c > 8% and DD > 4.5 years.
      CONCLUSION: HbA1c was a more dominant predictor for LnTP, LnHF and LnLF than DD
      in children with type 1 diabetes at rest. HRV reduced significantly from resting
      to exercise. However, the responses of HRV during exercise differ from the
      responses of HRV at rest.

PMID- 18063516
TI  - Preoperative diagnosis of gastric tumors by three-dimensional multidetector row
      ct and double contrast barium meal study: correlation with surgical and
      histologic results.
AB  - BACKGROUND/PURPOSE: Recent three-dimensional multidetector row computed
      tomography (3D MDCT) can provide detailed images of a gastric tumor, including
      its general contour, location and depth. We therefore evaluated the efficacy of
      MDCT in the differential diagnosis and staging of gastric tumors in patients
      prepared for surgery. METHODS: Seventy-nine patients with gastric tumors
      identified by gastric optical endoscopy were admitted for preoperative
      evaluation. All patients received double-contrast barium meal (DCBM) study and
      abdominal MDCT with 3D reconstruction before surgery. We compared the accuracy of
      MDCT with DCBM study in detecting and differentiating gastric tumors. In
      addition, the MDCT findings were correlated with surgical and pathologic results
      in gastric cancers for Borrmann type, T and N stages. RESULTS: Among the 79
      patients with gastric tumors, there were 24 cases of early gastric cancer, 40
      cases of advanced gastric cancer, 12 cases of gastrointestinal stromal tumor, and
      three cases of gastric lymphoma. Both MDCT and DCBM were very accurate in picking
      up the lesions (100%). The diagnostic accuracies of MDCT and DCBM were similar
      (94% vs. 96%) in differentiating mucosal and submucosal lesions as well as
      classification of Borrmann type in advanced gastric cancer (70% vs. 63%). In 64
      patients with gastric cancers, there was good correlation between MDCT images and
      pathology in 73% of T staging and 69% of N staging. CONCLUSION: MDCT has a
      similar high accuracy in the preoperative diagnosis of different gastric tumors
      compared with DCBM and provides additional information including tumor depth,
      lymph node and hepatic metastasis. Therefore, MDCT may be used as a primary tool
      for preoperative tumor diagnosis and staging.

PMID- 18063517
TI  - Primary nasal tuberculosis presenting with septal perforation.
AB  - Tuberculosis is a serious, worldwide health problem that affects people in many
      developing countries. The acquired immunodeficiency syndrome epidemic and the
      development of antibiotic-resistant strains of mycobacteria have contributed to
      the increasing international incidence of tuberculosis in recent years. Yet,
      extrapulmonary tuberculosis remains comparatively rare. We present the case of a
      44-year-old laborer who complained of bilateral nasal obstruction and postnasal
      drip for many years. Endoscopic examination disclosed septal perforation with
      marginal crusting. A biopsy of the marginal tissue was performed and Ziehl
      Neelsen staining revealed acid-fast bacilli. Subsequent to a 6-month course of
      antituberculous medication, the perforation remained, but the crusting subsided.

PMID- 18063518
TI  - Cervical sympathetic chain schwannoma.
AB  - Schwannomas are benign, slow-growing tumors that arise from Schwann cells of the
      nerve sheath. Those originating from the sympathetic cervical chain are rare.
      Herein, we present three cases of cervical sympathetic chain schwannoma (CSCS)
      and describe our experience with the clinical presentation, surgical management,
      and outcomes of patients with this pathology. All three patients were found to
      have a pulsatile, non-tender mass located at the level of the angle of the
      mandible without cervical nerve function deficit. On imaging study, the location
      of the mass between the prevertebral muscle and carotid artery with outward
      displacement of the carotid sheath is a typical characteristic of CSCS. Operative
      excision and sacrifice of a portion of the sympathetic chain remains the
      treatment of choice. Postoperative Horner's syndrome is predictable and vagus
      nerve dysfunction or first bite syndrome is also possible.

PMID- 18063519
TI  - Primary gastric angiosarcoma presenting as an asymptomatic gastric submucosal
      tumor.
AB  - Primary gastric angiosarcoma is a rare gastric tumor. Previously reported cases
      are limited and usually symptomatic. Preoperative diagnosis is difficult and
      should be differentiated from adenocarcinoma or gastrointestinal stromal tumor.
      We report a 55-year-old man with primary gastric angiosarcoma presenting as an
      asymptomatic gastric submucosal tumor. Abdominal ultrasonography showed a
      heteroechogenic tumor with several notably anechoic portions between the stomach
      and the gallbladder. Computed tomography showed that the tumor originated from
      the stomach, and upper gastrointestinal endoscopy showed a large gastric
      submucosal tumor at the lower body. Laparotomy was performed and a purple
      circumscribed tumor measuring 8.5 x 5.0 x 4.0 cm was found on the serosal aspect
      of the lower body. The tumor was soft and spongy with areas of hemorrhagic pools
      on section. Microscopically, the tumor was composed of proliferative neoplastic
      spindle to epithelioid cells. The neoplastic cells infiltrated and dissected the
      smooth muscle as vessel-forming architectures. On immunohistochemical study, the
      tumor cells were positive for CD34. These findings confirmed a diagnosis of
      primary gastric angiosarcoma. The patient has been well during the 11-month
      postoperative follow-up.

PMID- 18063520
TI  - Retinal detachment in a patient with microphthalmos and choroidal coloboma.
AB  - We report a rare case of retinal detachment with microphthalmos and choroidal
      coloboma. A 28-year-old man who had suffered from poor vision since early
      childhood was examined because of progressive deterioration of vision in his
      right eye. Examination of the anterior segment showed microphthalmos with
      microcornea and coloboma of the iris. Fundus examination revealed an inferior
      choroidal coloboma extending to the optic disc. The patient also had total
      bullous retinal detachment. Pars plana vitrectomy with silicone oil tamponade was
      performed, and the retina was reattached. Although rare, retinal detachment may
      develop in patients with microphthalmos and choroidal coloboma. Pars plana
      vitrectomy with additional scleral encircling buckle may be performed to treat
      this condition.

PMID- 18063521
TI  - A Novel Ael allele derived from a unique 816insG in Exon 7 of the ABO gene.
AB  - The ABO blood group system is the most important blood group system in
      transfusion medicine. In addition to the major A, B and O alleles, many rare
      alleles with weak expression of the A or B antigens on RBCs have been defined. We
      report here the molecular analysis of a novel A(el) allele. Exons 6 and 7 of the
      ABO gene were PCR-amplified, cloned and sequenced for the propositus, Mr C, who
      is a 56-year-old Taiwanese male and was incidentally observed to have an A(el)
      phenotype. His direct family members including wife, son and daughter were
      subsequently enrolled for further study. Three hundred random blood donors of AB
      phenotype served as control. A novel A(el) allele was uncovered from the
      propositus and his daughter, of which a unique 816insG mutation occurred on the
      A102 background that results in a frame shift leading to a 37-amino acid longer
      polypeptide than the normal A1 transferase, a finding similar to that of Ael01
      allele with 804insG. We found that the C family carried a novel A(el) allele that
      differs molecularly from seven A(el) alleles reported in the literature.

PMID- 18063522
TI  - The minimal erythema dose of broadband ultraviolet B in Taiwanese.
AB  - The purpose of this study was to determine the cutaneous response to UVB
      radiation in Taiwanese subjects. The relationships among minimal erythema dose
      (MED) of broadband UVB, Fitzpatrick's skin phototype, and skin color were
      examined in 61 healthy Taiwanese volunteers. Thirty-one females and 30 males were
      enrolled. Overall, the mean MED was 142.3 mJ/cm(2); there was no significant
      gender difference. The mean MEDs of subjects with Fitzpatrick skin types II, III,
      IV and V were 122.9 mJ/cm(2), 136.2 mJ/cm(2), 148.3 mJ/cm(2) and 165.0 mJ/cm(2),
      respectively. Both the mean MEDs and the lower MED limits increased with skin
      phototypes. To identify patients with abnormal photosensitivity, physicians could
      use these lower limits as reference values. In addition, different starting doses
      of broadband UVB phototherapy could be used for different skin phototypes.

PMID- 18063523
TI  - Estimation of UV exposure in Croatia over the summer using a simple approximate
      formula.
AB  - The Tropospheric Ultraviolet-Visible (TUV) model, version 4.2 developed by
      Madronich (2003) was used to estimate the extent of ultraviolet (UV) exposure of
      general population in Croatia over the summer. Solar noon values (13 h local
      time, CEST) of the ultraviolet index (UVI) for the period April to October 2004
      were calculated for 61 cities in Croatia. The results showed that the risk of
      sunburn at 13 h local time in clear weather was high between April and September
      (UVI > 7) and very high in July (UVI > 10). In July, the UVI exceeded 8 between
      11 h and 15 h local time. In this study, we developed a simple approximate
      formula to estimate UVI. The formula includes data on the time, date, altitude
      and clouds. The difference between our estimate and the TUV model for the summer
      months of June, July and August at 10 h to 16 h local time was less than 10%.

PMID- 18063524
TI  - Stress and work ability in oil industry workers.
AB  - This cross-sectional study conducted between March and June 2006 examined stress
      at work and work ability of 180 people with different workplaces within an oil
      company. Office, laboratory, and oil-field workers were invited to complete the
      "Occupational Stress Assessment Questionnaire--the Oil Industry Version and Work
      Ability Index (WAI) Questionnaire". The overall response rate was 69.4%, and the
      final sample size was 125 workers who completed the questionnaires (57 office, 41
      laboratory, 27 oil-field workers). Office, laboratory, and oil-field workers
      differed significantly with respect to age (P<0.001). The oldest were oil-field
      workers and the youngest were office workers. The average WAI score for office
      workers was 44.9, for laboratory workers 43.2 and for field workers 39.7,
      indicating satisfying work ability. After adjusting for age, the difference in
      WAI score between the groups of workers was still significant (P<0.001). Over 75%
      of all workers believed their job was stressful, but the perception of specific
      stressors depended on the workplace.

PMID- 18063525
TI  - Dynamics of the lung function in asbestos pleural disease.
AB  - As a rule, asbestosis is a disease of workers who are occupationally exposed to
      inhalation of asbestos dust, leaving permanent alterations on the lung parenchyma
      or pleura. In our ten-year study, we investigated 318 workers with pleural
      asbestosis from whom we took medical history which included occupational exposure
      to asbestos, radiological examinations and lung function, which is mandatory for
      the diagnosis and the follow up of the disease. We analysed functional parameters
      such as forced vital capacity (FVC) and forced expiratory volume in the first
      second (FEV1) and intermediate forced expiratory flow at 25% to 75% (FEF25%-75%).
      In addition, we investigated the predicted values of functional parameters
      according to smoking and non-smoking habits. We found a significant reduction in
      vital capacity, particularly in smokers after 25 years of exposure to asbestos.
      During the first 15 years, values of vital capacity on the group basis remained
      inside the 80% of the normal values and were not significant for assessing the
      dynamics of the lung function. To better assess the effects of occupational
      asbestos exposure, it is necessary to interpret lung function data not only on
      the group basis, but also for each subject individually.

PMID- 18063526
TI  - Determination of mite allergens in house dust using the enzyme immunoassay.
AB  - The aim of this study was to determine the level of two major mite allergens
      Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1)
      in 30 urban homes in Zagreb, Croatia, using the enzyme immunoassay with two
      monoclonal antibodies which has been established as the reference method for
      indoor allergen analysis. Dust samples were taken by vacuuming a carpeted area
      and collected on cellulose filters. The ranges of Der p 1 and Der f 1 were (0.1
      12.5) microg g-1 (median 0.32 microg g-1) and (0.1-31.2) microg g-1 (median 0.35
      microg g-1), respectively. Der p 1 and Der f 1 (>2 microg g-1) associated with
      increased risk of sensitization to mite allergens were found in approximately 16%
      homes for each allergen. The sum of allergen (Der p 1 + Der f 1) exceeded the
      lower threshold in 27% of homes. Analytical evaluation of the ELISA assay showed
      satisfactory results for precision (intra-assay CV <6.9%, inter-assay CV<13.3%),
      accuracy (91% to 93%), and sensitivity (2 ng mL-1). The ELISA assay for the
      measurement of dust mite allergens demonstrated very good analytical
      characteristics for routine laboratory use, and will provide the essential basis
      for our future studies of various indoor allergens.

PMID- 18063527
TI  - Comparison between dynamic headspace and headspace solid-phase microextraction
      for gas chromatography of BTEX in urine.
AB  - The aim of this study was to compare two extraction procedures: dynamic headspace
      purge and trap (PT) and headspace solid-phase microextraction (HS-SPME) for gas
      chromatographic determination of benzene, toluene, ethylbenzene, and isomeric
      xylenes (BTEX) in urine with photoionization (PID) and mass spectrometric (MS)
      detection, respectively. Both methods showed linearity in the range of interest
      [(50-2000) ng L-1], good accuracy (80% to 100%), and repeatability (RSD< or
      =11%). Detection limits were in the low ng L-1 level for both methods, although
      slightly greater sensitivity was found for the PT method. In comparison with PT,
      HS-SPME was simpler and required less time for analysis. Although the analytical
      features of both examined methods are appropriate for biomonitoring of
      environmental exposure to BTEX, only the HS-SPME-GC-MS method is recommended for
      routine analysis of BTEX in urine. The method was applied for the quantitative
      analysis of BTEX in urine samples collected from non-smokers (n=10) and smokers
      (n=10).

PMID- 18063528
TI  - Interaction between certain moulds and aflatoxin B1 producer Aspergillus flavus
      NRRL 3251.
AB  - The objective of this study was to evaluate biotic interaction between some mould
      species and active producer of aflatoxin B1 Aspergillus flavus NRRL 3251, co
      cultured in yeast-extract sucrose (YES) broth. Twenty-five mould strains of
      Alternaria spp., Cladosporium spp., Mucor spp., A. flavus and A. niger, used as
      biocompetitive agents, were isolated from outdoor and indoor airborne fungi,
      scrapings of mouldy household walls, and from stored and post-harvest maize.
      Aflatoxin B1 was extracted from mould biomasses with chloroform and detected
      using the multitoxin TLC method. The results confirm antagonistic interaction
      between all strains tested. With Alternaria spp. and Cladosporium spp., aflatoxin
      B1 production decreased 100%, compared to detection in a single culture of A.
      flavus NRRL 3251 (Cmean=18.7 microg mL-1). In mixed cultures with Mucor spp.,
      aflatoxin B1 levels dropped to (5.6-9.3) microg mL-1, and the inhibition was from
      50% to 70%. Four of five aflatoxin non-producing strains of A. flavus interfered
      with aflatoxin production in mixed culture, and reduced AFB1 productivity by
      100%. One strain showed a lower efficacy in inhibiting AFB1 production (80%) with
      a detectable amount of AFB1 3.7 microg mL-1 when compared to control. A decrease
      in toxin production was also observed in dual cultivation with A. niger strains.
      It resulted in 100% reduction in three strains), 90% reduction in one strain
      (Cmean=1.9 microg mL-1) and 80% reduction in one strain (Cmean=3.7 microg mL-1)
      inhibition.

PMID- 18063529
TI  - [Individual differences and sleep deprivation effects].
AB  - Contemporary lifestyle and different life circumstances often require that
      individuals restrict their sleep duration and change their sleep schedule. That
      often leads to sleep deprivation. Former studies showed that sleep deprivation
      effects on the physiological and psychological functioning of an individual
      depended on numerous factors such as type of sleep deprivation, previous sleep
      duration, time of day when the effects were examined, characteristics of tasks
      performed, and the subject's motivation. This paper discusses the effects of
      sleep deprivation and the existence of stable individual differences in those
      effects, named "vulnerability to sleep loss". Recent studies indicate that some
      characteristics of the subjects could help predict systematic and robust sleep
      deprivation effects, such as age, sex and personality characteristics.
      Furthermore, the article discusses the importance of individual differences in
      specific characteristics related to sleep and wakefulness like those in preferred
      circadian phase, sleep need, individual level of sleepiness, and the ability to
      fall asleep quickly. So far, studies of individual characteristics did not result
      in consistent conclusions about their predictive importance for vulnerability to
      sleep loss. Further studies directed at this problem could help identify
      individuals who are more vulnerable to sleep loss, and contribute to personal and
      public safety of night work.

PMID- 18063530
TI  - [Effects of radiofrequency electromagnetic fields on mammalian spermatogenesis].
AB  - This article reviews studies about the effects of radiofrequency electromagnetic
      (RF EM) fields on male reproductive system and reproductive health in mammals.
      According to current data, there are almost 4 million active mobile phone lines
      in Croatia while this number has risen to 2 billion in the world. Increased use
      of mobile technology raises scientific and public concern about possible
      hazardous effects of RF fields on human health. The effects of radiofrequencies
      on reproductive health and consequences for the offspring are still mainly
      unknown. A number of in vivo and in vitro studies indicated that RF fields could
      interact with charged intracellular macromolecular structures. Results of several
      laboratory studies on animal models showed how the RF fields could affect the
      mammalian reproductive system and sperm cells. Inasmuch as, in normal
      physiological conditions spermatogenesis is a balanced process of division,
      maturation and storage of cells, it is particularly vulnerable to the chemical
      and physical environmental stimuli. Especially sensitive could be the
      cytoskeleton, composed of charged proteins; actin, intermedial filaments and
      microtubules. Cytoskeleton is a functional and structural part of the cell that
      has important role in the sperm motility, and is actively involved in the
      morphologic changes that occur during mammalian spermiogenesis.

PMID- 18063531
TI  - [Analysis of polychlorinated biphenyls and organochlorine pesticides in pine
      needles].
AB  - This paper presents a review of methods for the analysis of polychlorinated
      biphenyls (PCBs) and organochlorine pesticides (OCPs) in pine needles. These
      compounds are lipophilic, they accumulate in the biotic and abiotic part of the
      environment in which they are persistent, and their use is forbidden or
      restricted due to harmful effects on human and animal health. Pine needles are
      convenient for monitoring the levels of organochlorine compounds in the air
      because they accumulate them in wax with which they are covered. However, the
      presence of many other compounds makes them complex for analysis. Analytical
      methods for determining organochlorine compounds in pine needles include sample
      collection, extraction of compounds with a suitable solvent, extract clean-up
      from unwanted compounds and qualitative and quantitative analysis. PCBs and OCPs
      are present in pine needles in traces, and every part of the analytical procedure
      has to be as efficient and selective as possible.

PMID- 18063532
TI  - Nanotoxicology for safe and sustainable nanotechnology.
AB  - Nanotechnology is the term given to those areas of science and engineering where
      the phenomena take place at nanoscale dimensions. Nanoparticles are particles
      with <100 nm in one dimension. They have different physical, chemical, electrical
      and optical properties than those that occur in bulk samples of the same
      material. Understanding these nanoscale properties and finding ways to engineer
      new nanomaterials will have a revolutionary impact, from more efficient energy
      generation and data storage to improved methods for diagnosing and treating
      diseases. Nanotechnology is poised to become a major factor in the world's
      economy and part of our everyday lives in the near future. Hundreds of tonnes of
      nanoparticles already enter the environment annually, but still very little is
      known of their interactions with biological systems. Recent studies indicate that
      some nanoparticles are not completely benign to biological and environmental
      targets. The challenge for toxicologists is to identify key factors that can be
      used to predict toxicity, permit targeted screening, and allow material
      scientists to generate new, safer nanoparticles with this structure-toxicity
      information in mind. The aim of this paper is to summarize some known facts about
      nanomaterials and discuss future perspectives, regulatory issues and tasks of the
      emerging branch of toxicology, that is, nanotoxicology.

PMID- 18063533
TI  - [Effects of volcanic eruptions on environment and health].
AB  - Volcanoes pose a threat to almost half a billion people; today there are
      approximately 500 active volcanoes on Earth, and every year there are 10 to 40
      volcanic eruptions. Volcanic eruptions produce hazardous effects for the
      environment, climate, and the health of the exposed persons, and are associated
      with the deterioration of social and economic conditions. Along with magma and
      steam (H2O), the following gases surface in the environment: carbon dioxide (CO2)
      and sulphur dioxide (SO2), carbon monoxide (CO), hydrogen sulphide (H2S), carbon
      sulphide (CS), carbon disulfide (CS2), hydrogen chloride (HCl), hydrogen (H2),
      methane (CH4), hydrogen fluoride (HF), hydrogen bromide (HBr) and various organic
      compounds, as well as heavy metals (mercury, lead, gold).Their unfavourable
      effects depend on the distance from a volcano, on magma viscosity, and on gas
      concentrations. The hazards closer to the volcano include pyroclastic flows,
      flows of mud, gases and steam, earthquakes, blasts of air, and tsunamis. Among
      the hazards in distant areas are the effects of toxic volcanic ashes and problems
      of the respiratory system, eyes and skin, as well as psychological effects,
      injuries, transport and communication problems, waste disposal and water supplies
      issues, collapse of buildings and power outage. Further effects are the
      deterioration of water quality, fewer periods of rain, crop damages, and the
      destruction of vegetation. During volcanic eruptions and their immediate
      aftermath, increased respiratory system morbidity has been observed as well as
      mortality among those affected by volcanic eruptions. Unfavourable health effects
      could partly be prevented by timely application of safety measures.

PMID- 18063534
TI  - If you build it, will they come?

PMID- 18063535
TI  - TopoTarget responds.

PMID- 18063536
TI  - Oral chemotherapy medications: the need for a nurse's touch.
AB  - Since 2005, many oral chemotherapy agents have been released. Nurses often are
      not directly involved with patients who receive oral agents. Difficulties with
      adherence, safety, patient teaching, and access to oral agents can hinder
      treatment. Nurses can increase adherence and keep patients safe by developing
      standardized written prescriptions, encouraging the use of patient diaries,
      offering dosage calendars, and supplying contact information for an office
      pharmacist.

PMID- 18063537
TI  - Clostridium difficile.
AB  - CASE STUDY: George, a 55-year-old retired businessman with a diagnosis of
      myelofibrosis, underwent an allogeneic stem cell transplantation from his human
      leukocyte antigen-matched brother in June 2006. He was admitted to the hospital
      for a possible flare of graft-versus-host disease (GVHD) of the gut. His
      medications included tacrolimus, budesonide, and bechlamethasone for
      immunosuppression and pantoprazole. A stool sample was positive for Clostridium
      difficile toxin A on October 31, 2006, and he was started on oral metronidazole.

PMID- 18063538
TI  - Delirium: an under-recognized problem.
AB  - CASE STUDY: Ms. G, a 78-year-old woman with a history of heart failure and a left
      ventricular ejection fraction of 45%, had an exploratory laparotomy with colon
      resection and colostomy two days ago for an obstructive stage IIIB adenocarcinoma
      of the colon. She is a patient on a general surgical unit. Upon assessment at 7
      am, Ms. G was easily aroused and oriented. She has a patient-controlled analgesia
      (PCA) pump for postoperative pain control with 1 mg of morphine available every
      30 minutes; she used a total of 4 mg of morphine via IV since midnight. Ms. G
      requires belladonna and opium suppositories about every eight hours to treat
      bladder spasms associated with her urinary catheter.

PMID- 18063540
TI  - Distress assessment: practice change through guideline implementation.
AB  - Most nurses agree that incorporating evidence into practice is necessary to
      provide quality care, but barriers such as time, resources, and knowledge often
      interfere with the actual implementation of practice change. Published practice
      guidelines are one source to direct practice; this article focuses on the use of
      the National Comprehensive Cancer Network's Clinical Practice Guidelines for
      Oncology: Distress Management, which articulate standards and demonstrate
      assessment for psychosocial distress. Planning for the implementation of the
      guidelines in a feasibility pilot in a busy radiation oncology clinic is
      described. Results indicate that adding a distress assessment using the distress
      thermometer and problem checklist did not present substantial burden to nurses in
      the clinic or overwhelm the mental health, pastoral care, or oncology social work
      referral sources with more patients. Understanding distress scores and problems
      identified by patients helped the nurses direct education interventions and
      referrals appropriately; improved patient satisfaction scores reflected this.

PMID- 18063539
TI  - Is ondansetron more effective than granisetron for chemotherapy-induced nausea
      and vomiting? A review of comparative trials.
AB  - Nausea and vomiting are two of the most distressing side effects of chemotherapy.
      Guidelines recommend the use of 5-HT3 receptor antagonists as a pharmacologic
      intervention for acute and delayed nausea and vomiting for moderately and highly
      emetogenic chemotherapy. Although newer antiemetics and 5-HT3 receptor
      antagonists are available, ondansetron and granisetron still are used widely. A
      review of the literature was conducted to identify trials that compared the
      antiemetic efficacy of ondansetron and granisetron. Studies were identified by
      searching the PubMed, EMBASE, Ovid MEDLINE, CINAHL, and Evidence-Based Medicine
      Reviews databases. The six studies reviewed in this article were either a meta
      analysis; a randomized, controlled trial; or another type of research study
      published from 2000 to date. The results reported in the studies reveal that
      ondansetron and granisetron have equal antiemetic efficacy in reducing or
      eliminating chemotherapy-induced nausea and vomiting (CINV), with the evidence
      classified as good based on U.S. Preventive Services Task Force criteria for
      judging the strength of the overall evidence. Although side effects of
      ondansetron and granisetron have been reported, they normally are mild and of
      brief duration, not severe or lasting enough to warrant discontinuation.

PMID- 18063541
TI  - Back to basics: assessment, communication, caring, and follow-up: a lesson from a
      couple's journey with multiple myeloma.
AB  - Ian was a patient with multiple myeloma. His wife, Judi, chronicled their journey
      and experiences with myeloma and the healthcare system. Through her own eyes,
      Judi provides a view of the positive and negative consequences of actions or
      omissions by the healthcare team. The other authors, oncology nurses affiliated
      with a myeloma treatment center, collaborated with Judi to tell her story and
      remind oncology nurses that they can and do make a difference when focus is
      placed on the basics: assessment, communication, caring, and follow-up.

PMID- 18063542
TI  - Clinical updates and nursing considerations for patients with multiple myeloma.
AB  - Multiple myeloma accounts for approximately 1% of all new cancers and is
      characterized by abnormal plasma cell proliferation in the bone marrow. As a
      result, many patients develop bone lesions, hypercalcemia, anemia, and renal
      impairment. Although no cure exists for multiple myeloma, current treatments,
      such as oral melphalan and prednisone, can slow disease progression and prolong
      overall survival. Several new therapeutic options show promise: lenalidomide,
      thalidomide, liposomal doxorubicin, and bortezomib. Clinical research presented
      at the 2006 meeting of the American Society of Hematology, the 2007 meeting of
      the American Society of Clinical Oncology, and the 11th International Myeloma
      Workshop showed that newer therapeutic combinations were well tolerated and
      effective in patients with multiple myeloma. Oncology nurses, with their
      specialized knowledge of treatment administration and monitoring and their
      expertise in patient education, have an important role in the management of
      patients with multiple myeloma to help improve overall survival and quality of
      life. As newer regimens become available, oncology nurses must be aware of
      factors that optimize outcomes to help patients understand the benefits of
      treatment, how to manage side effects, and the importance of treatment adherence.

PMID- 18063543
TI  - Multiple myeloma and treatment-related thromboembolism: oncology nurses' role in
      prevention, assessment, and diagnosis.
AB  - Immunomodulating agents such as thalidomide and its newly emerged derivative,
      lenalidomide, are becoming increasingly popular in the treatment of multiple
      myeloma because of their ability to combat drug resistance. Clinical trials
      suggest that thalidomide and lenalidomide are effective in all stages of multiple
      myeloma treatment-new diagnoses, stem cell transplantations, maintenance therapy,
      and relapsed or refractory disease. The drugs are most efficacious when combined
      with additional chemotherapeutic agents and/or corticosteroids. However, deep
      vein thrombosis and other thromboembolic events are associated with the treatment
      regimens. Oncology nurses must understand the pharmacologic properties of the
      drugs and the potentially life-threatening complications associated with them. To
      provide the highest standard of care, oncology nurses must play a vital role in
      the prevention, diagnosis, and management of thromboembolic events through
      awareness of the clinical problem, assessment tools, and thromboembolic
      prophylactic regimens.

PMID- 18063544
TI  - Prostate cancer: a chronic illness.
AB  - Prostate cancer is the most frequently diagnosed malignancy and the second
      leading cause of cancer death in men. The 10-year survival rate for all stages of
      prostate cancer is 93%. Men with prostate cancer live with the disease for many
      years, and the side effects of the disease and treatments have physical and
      psychosocial implications for the patient, spouse, and family. This case study
      explores the evolution of a patient with prostate cancer, from time of diagnosis
      through treatment decision making and ultimately end of life. Discussion of the
      implications for practice and research is included.

PMID- 18063546
TI  - Nutritional support during radiotherapy for head and neck cancer: the role of
      prophylactic feeding tube placement.
AB  - Significant weight loss and resultant malnutrition in patients undergoing
      radiotherapy for head and neck carcinomas are recognized and preventable clinical
      concerns. Morbidity related to weight loss during treatment may include
      dehydration, hospitalization, compromised treatment efficacy, and reduced quality
      of life and may impact survival. Malnutrition effects on wound healing may
      prolong recovery following treatment and increase the risk of morbidity for those
      undergoing subsequent salvage surgery. Multiple interventions have been
      implemented to help ameliorate the impact of treatment on weight loss and
      nutritional status, including the use of percutaneous endoscopic gastrostomy
      (PEG) tubes. The value of prophylactic PEG tube placement at treatment initiation
      increasingly is being recognized, and evidence suggests that patients experience
      better outcomes. Criteria for patient selection have not been defined completely,
      and a great deal of variation in clinical practice exists, contributing to
      underuse of this supportive intervention. According to a literature review,
      patients who require therapeutic PEG tube placement in response to significant
      weight loss during treatment suffer greater morbidity than patients who receive
      PEG tubes prophylactically. Understanding patient-, tumor-, and treatment-related
      risk factors to systematically identify patients most likely to benefit from
      prophylactic PEG tube placement is an important aspect of nursing care.

PMID- 18063545
TI  - Reducing prostate cancer morbidity and mortality in African American men: issues
      and challenges.
AB  - Prostate cancer is the most commonly diagnosed cancer in men in the United
      States. It disproportionately affects African American men when compared to other
      ethnic groups. African American men are two to three times more likely to die of
      prostate cancer than white men. The reasons for the disparity remain unclear, but
      several factors may be involved, such as age, race, nationality, nutrition,
      exercise, and family history of cancer. Detection of prostate cancer in high-risk
      African Americans is important but continues to be controversial. This article
      reviews the current issues and challenges regarding prostate cancer in African
      American men. Nurses play a vital role in the health care and education of
      patients; therefore, they must be aware of the issues.

PMID- 18063547
TI  - Intraperitoneal chemotherapy: implications beyond ovarian cancer.
AB  - The National Cancer Institute (NCI) announced in January 2006 the use of
      intraperitoneal (IP) combined with IV chemotherapy postoperatively as the
      preferred treatment method for advanced ovarian cancer. The announcement
      stimulated the need for oncology nurses to become familiar with IP chemotherapy
      administration and patient management guidelines. IP administration allows a high
      concentration of chemotherapy to come into direct contact with tumors and
      surrounding tissues and organs. IP chemotherapy also is administered in clinical
      trials and some clinical settings for other histologies, such as low-grade
      gastrointestinal carcinoma and appendiceal carcinoma, which tend to spread
      locally before invading the bloodstream. Local-regional chemotherapy potentially
      is an ideal treatment for local spread of those peritoneal carcinomas. Overall
      side effects from regional treatment are less severe than with systemic
      treatment. Oncology nurses can help minimize and alleviate discomfort associated
      with IP chemotherapy administration. This article focuses on nursing management
      strategies for patients receiving IP chemotherapy for ovarian cancer and other
      peritoneal carcinomatosis.

PMID- 18063548
TI  - Putting evidence into practice: evidence-based interventions for chemotherapy
      induced peripheral neuropathy.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) continues to be a significant,
      debilitating symptom resulting from the administration of neurotoxic chemotherapy
      for the treatment of cancer. CIPN is an important consequence of cancer treatment
      because of its potential impact on physical functioning and quality of life.
      Oncology nurses play an important role in assessing, monitoring, and educating
      clients about CIPN. Despite investigations concerning pharmacologic and
      nonpharmacologic approaches to either preventing or minimizing the neurotoxicity
      resulting from certain chemotherapeutic agents, evidence to support the
      interventions is lacking. This article presents information concerning CIPN and
      summarizes the evidence for pharmacologic and nonpharmacologic approaches to the
      prevention and treatment of CIPN.

PMID- 18063549
TI  - Nursing guidelines for managing infections in patients with chronic lymphocytic
      leukemia.
AB  - Infections are a primary cause of death in patients with chronic lymphocytic
      leukemia (CLL). Such individuals are particularly susceptible to infectious
      complications stemming from immune deficits associated with the primary disease
      process and with immunosuppression secondary to treatment. Although the recent
      availability of new treatment modalities and more aggressive therapies are
      improving outcomes for patients with CLL, standardized approaches are needed so
      that nurses can monitor for and manage infections. The aim is overall reduction
      in morbidity and mortality, as well as improvement in quality of life. The
      current pharmacologic therapies for CLL are alkylating agents, purine nucleoside
      analogs, monoclonal antibodies, and combinations of those therapies, which may
      present their own unique risks for and different spectra of infectious events.
      This article provides an overview of the known risks for developing infections in
      CLL, as well as nursing guidelines for monitoring and managing patients with CLL.

PMID- 18063550
TI  - Oncology-critical care nursing collaboration: recommendations for optimizing
      continuity of care of critically ill patients with cancer.
AB  - Highly specialized care is required for critically ill patients with cancer, but
      continuity of care equally is important to their survival when they are admitted
      to the critical care setting. The use of oncology nurses as liaisons to critical
      care nurses may help ensure the continuity of care and reduce rates of morbidity
      and mortality. This article provides a framework for collaborative consultation
      between oncology and critical care nurses.

PMID- 18063551
TI  - Developing a multidisciplinary geriatric oncology program in a community cancer
      center.
AB  - Cancer is a disease of older adults, and with unprecedented growth in the number
      of people entering late adulthood, an increasing need exists for specialized
      services and programs to address the needs of older adults with cancer. Few
      examples in the literature detail development of a geriatric oncology program.
      This article describes a pilot project undertaken by a community cancer center to
      develop a specialized program for older adults with cancer by identifying local
      demographics and population needs. It also describes a replicable plan for the
      development of a geriatric oncology program, which demonstrates how nursing can
      benefit from collaboration with other disciplines such as social work and
      psychology in service provision.

PMID- 18063553
TI  - Can cancer be diagnosed with a blood test during routine examinations?
AB  - Cancer can be detected in asymptomatic patients by a blood draw for tumor
      biomarkers during routine examinations in a doctor's office. The reliability of
      tumor biomarkers to diagnose cancer in asymptomatic patients is a frequently
      asked question in general practice as well as in an oncology setting.

PMID- 18063554
TI  - Treatment of aspergillosis in an immunocompetent patient: a multidisciplinary
      approach.
AB  - CASE STUDY: P.J. was a 69-year-old woman who was referred to a large cancer
      center for an evaluation of brain and lung masses presumed to be cancerous
      lesions. During the three months before the referral, P.J. had experienced a
      gradual 40 lb weight loss, shortness of breath with exertion, chest pain, lip
      tremor, edema and progressive weakening of lower extremities, overall fatigue,
      and increasing balance and gait disturbances. Her diagnostic workup revealed
      aspergillosis in her lungs and brain. This case study reports the process of
      differentiating between cancer and fungal disease, antifungal treatment
      modalities used, and the multidisciplinary management approach used in the care
      of P.J.

PMID- 18063555
TI  - A parasitoid wasp uses landmarks while monitoring potential resources.
AB  - Social insects and insects that provision nests are well known to have complex
      foraging behaviour involving repeated visits to learned locations. Other insects
      do not forage from a central location and are generally assumed to respond to
      resources by simple attraction without spatial memory. This simple response to
      resource cues is generally taken as giving rise to patterns of resource use that
      correspond directly to resource distribution. By contrast, the solitary
      parasitoid wasp Hyposoter horticola monitors the locations of multiple potential
      hosts (butterfly eggs) for up to several weeks, until the hosts become
      susceptible to parasitism. Essentially all hosts in the landscape are found, and
      one-third of them are parasitized, independent of host density. Here, we show
      that the wasps do not relocate hosts using odour markers previously left by
      themselves or other foragers, nor do they find the eggs anew repeatedly. Instead,
      the wasps relocate host eggs by learning the position of the eggs relative to
      visual landmarks. The anticipatory foraging behaviour presented here is a key to
      the wasp's exceptionally stable population dynamics.

PMID- 18063559
TI  - The influence of genetic variation on gene expression.
AB  - The view that changes to the control of gene expression rather than alterations
      to protein sequence are central to the evolution of organisms has become
      something of a truism in molecular biology. In reality, the direct evidence for
      this is limited, and only recently have we had the ability to look more globally
      at how genetic variation influences gene expression, focusing upon inter
      individual variation in gene expression and using microarrays to test for
      differences in mRNA levels. Here, we review the scope of these experimental
      analyses, what they are designed to tell us about genetic variation, and what are
      their limitations from both a technical and a conceptual viewpoint. We conclude
      that while we are starting to understand the impact of this class of genetic
      variation upon steady-state mRNA levels, we are still far from identifying the
      potential phenotypic and evolutionary outcomes.

PMID- 18063560
TI  - Human medial frontal cortex activity predicts learning from errors.
AB  - Learning from errors is a critical feature of human cognition. It underlies our
      ability to adapt to changing environmental demands and to tune behavior for
      optimal performance. The posterior medial frontal cortex (pMFC) has been
      implicated in the evaluation of errors to control behavior, although it has not
      previously been shown that activity in this region predicts learning from errors.
      Using functional magnetic resonance imaging, we examined activity in the pMFC
      during an associative learning task in which participants had to recall the
      spatial locations of 2-digit targets and were provided with immediate feedback
      regarding accuracy. Activity within the pMFC was significantly greater for errors
      that were subsequently corrected than for errors that were repeated. Moreover,
      pMFC activity during recall errors predicted future responses (correct vs.
      incorrect), despite a sizeable interval (on average 70 s) between an error and
      the next presentation of the same recall probe. Activity within the hippocampus
      also predicted future performance and correlated with error-feedback-related pMFC
      activity. A relationship between performance expectations and pMFC activity, in
      the absence of differing reinforcement value for errors, is consistent with the
      idea that error-related pMFC activity reflects the extent to which an outcome is
      "worse than expected."

PMID- 18063561
TI  - Neurotensin receptor involvement in the rise of extracellular glutamate levels
      and apoptotic nerve cell death in primary cortical cultures after oxygen and
      glucose deprivation.
AB  - In view of the ability of neurotensin (NT) to increase glutamate release, the
      role of NT receptor mechanisms in oxygen-glucose deprivation (OGD)-induced
      neuronal degeneration in cortical cultures has been evaluated by measuring
      lactate dehydrogenase (LDH) levels, mitochondrial dehydrogenase activity with 3
      [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide levels, and
      microtubule-associated protein 2 (MAP2) immunoreactivity. Apoptotic nerve cell
      death was analyzed measuring chromatin condensation with Hoechst 33258, annexin V
      staining, and caspase-3 activity. Furthermore, the involvement of glutamate
      excitotoxicity in the neurodegeneration-enhancing actions of NT was analyzed by
      measurement of extracellular glutamate levels. NT enhanced the OGD-induced
      increase of LDH, endogenous extracellular glutamate levels, and apoptotic nerve
      cell death. In addition, the peptide enhanced the OGD-induced loss of
      mitochondrial functionality and increase of MAP2 aggregations. These effects were
      blocked by the neurotensin receptor 1 (NTR1) antagonist SR48692. Unexpectedly,
      the antagonist at 100 nM counteracted not only the NT effects but also some OGD
      induced biochemical and morphological alterations. These results suggest that
      NTR1 receptors may participate in neurodegenerative events induced by OGD in
      cortical cultures, used as an in vitro model of cortical ischemia. The NTR1
      receptor antagonists could provide a new tool to explore the clinical
      possibilities and thus to move from chemical compound to effective drug.

PMID- 18063562
TI  - Time course of competition for visual processing resources between emotional
      pictures and foreground task.
AB  - High-arousing emotional stimuli facilitate early visual cortex, thereby acting as
      strong competitors for processing resources in visual cortex. The present study
      used an electrophysiological approach for continuously measuring the time course
      of competition for processing resources in the visual pathway arising from
      emotionally salient but task-irrelevant input while performing a foreground
      target detection task. Steady-state visual evoked potentials (SSVEPs) were
      recorded to rapidly flickering squares superimposed upon neutral and emotionally
      high-arousing pictures, and variations in SSVEP amplitude over time were
      calculated. As reflected in SSVEP amplitude and target detection rates, arousing
      emotional background pictures withdrew processing resources from the detection
      task compared with neutral ones for several hundred milliseconds after stimulus
      onset. SSVEP amplitude was found to bear a close temporal relationship with
      accurate target detection as a function of time after stimulus onset.

PMID- 18063563
TI  - Negative BOLD with large increases in neuronal activity.
AB  - Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI)
      is widely used in neuroscience to study brain activity. However, BOLD fMRI does
      not measure neuronal activity directly but depends on cerebral blood flow (CBF),
      cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO(2))
      consumption. Using fMRI, CBV, CBF, neuronal recordings, and CMRO(2) modeling, we
      investigated how the signals are related during seizures in rats. We found that
      increases in hemodynamic, neuronal, and metabolic activity were associated with
      positive BOLD signals in the cortex, but with negative BOLD signals in
      hippocampus. Our data show that negative BOLD signals do not necessarily imply
      decreased neuronal activity or CBF, but can result from increased neuronal
      activity, depending on the interplay between hemodynamics and metabolism. Caution
      should be used in interpreting fMRI signals because the relationship between
      neuronal activity and BOLD signals may depend on brain region and state and can
      be different during normal and pathological conditions.

PMID- 18063564
TI  - Reduced resting-state brain activity in the "default network" in normal aging.
AB  - Normal aging is associated with cognitive decline. Functions such as attention,
      information processing, and working memory are compromised. It has been
      hypothesized that not only regional changes, but also alterations in the
      integration of regional brain activity (functional brain connectivity) underlie
      the observed age-related deficits. Here, we examined the functional properties of
      brain networks based on spontaneous fluctuations within brain systems using
      functional magnetic resonance imaging. We hypothesized that functional
      connectivity of intrinsic brain activity in the "default-mode" network (DMN) is
      affected by normal aging and that this relates to cognitive function. Ten younger
      and 22 older subjects were scanned at "rest," that is, lying awake with eyes
      closed. Our results show decreased activity in older versus younger subjects in 2
      resting-state networks (RSNs) resembling the previously described DMN, containing
      the superior and middle frontal gyrus, posterior cingulate, middle temporal
      gyrus, and the superior parietal region. These results remain significant after
      correction for RSN-specific gray matter volume. The relevance of these findings
      is illustrated by the correlation between reduced activity of one of these RSNs
      and less effective executive functioning/processing speed in the older group.

PMID- 18063565
TI  - Cochlear implants stimulate activity-dependent CREB pathway in the deaf auditory
      cortex: implications for molecular plasticity induced by neural prosthetic
      devices.
AB  - Neural activity modulates the maturation of synapses and their organization into
      functional circuits by regulating activity-dependent signaling pathways.
      Phosphorylation of cyclic AMP/Ca(2+)-responsive element-binding protein (CREB) is
      widely accepted as a stimulus-inducible event driven by calcium influx into
      depolarized neurons. In turn, phosphorylated CREB (pCREB) activates the
      transcription of brain-derived neurotrophic factor (BDNF), which is needed for
      synaptic transmission and long-term potentiation. We examined how these molecular
      events are influenced by sensorineural hearing loss and long-term reactivation
      via cochlear implants. Sensorineural hearing loss reduced the expression of pCREB
      and BDNF. In contrast, deafened animals subject to long-term, unilateral
      intracochlear electrical stimulation exhibited an increased expression of pCREB
      and BDNF in the contralateral auditory cortical neurons, relative to ipsilateral
      ones. These changes induced by cochlear implants are further accompanied by the
      activation of the mitogen-activated protein kinase (MAPK) signaling pathway,
      which has been implicated in long-lasting forms of synaptic plasticity. Because
      CREB and BDNF are critical modulators of synaptic plasticity, our data describe
      for the first time possible molecular candidate genes, which are altered in the
      auditory cortex, following cochlear implantation. These findings provide insights
      into adaptive, molecular mechanisms recruited by the brain upon functional
      electrical stimulation by neural prosthetic devices.

PMID- 18063566
TI  - Neural correlates of visually induced self-motion illusion in depth.
AB  - Optic-flow fields can induce the conscious illusion of self-motion in a
      stationary observer. Here we used functional magnetic resonance imaging to reveal
      the differential processing of self- and object-motion in the human brain.
      Subjects were presented a constantly expanding optic-flow stimulus, composed of
      disparate red-blue dots, viewed through red-blue glasses to generate a vivid
      percept of three-dimensional motion. We compared the activity obtained during
      periods of illusory self-motion with periods of object-motion percept. We found
      that the right MT+, precuneus, as well as areas located bilaterally along the
      dorsal part of the intraparietal sulcus and along the left posterior
      intraparietal sulcus were more active during self-motion perception than during
      object-motion. Additional signal increases were located in the depth of the left
      superior frontal sulcus, over the ventral part of the left anterior cingulate, in
      the depth of the right central sulcus and in the caudate nucleus/putamen. We
      found no significant deactivations associated with self-motion perception. Our
      results suggest that the illusory percept of self-motion is correlated with the
      activation of a network of areas, ranging from motion-specific areas to regions
      involved in visuo-vestibular integration, visual imagery, decision making, and
      introspection.

PMID- 18063568
TI  - Use of a multi-thermal washer for DNA microarrays simplifies probe design and
      gives robust genotyping assays.
AB  - DNA microarrays are generally operated at a single condition, which severely
      limits the freedom of designing probes for allele-specific hybridization assays.
      Here, we demonstrate a fluidic device for multi-stringency posthybridization
      washing of microarrays on microscope slides. This device is called a multi
      thermal array washer (MTAW), and it has eight individually controlled heating
      zones, each of which corresponds to the location of a subarray on a slide. Allele
      specific oligonucleotide probes for nine mutations in the beta-globin gene were
      spotted in eight identical subarrays at positions corresponding to the
      temperature zones of the MTAW. After hybridization with amplified patient
      material, the slides were mounted in the MTAW, and each subarray was exposed to
      different temperatures ranging from 22 to 40 degrees C. When processed in the
      MTAW, probes selected without considering melting temperature resulted in
      improved genotyping compared with probes selected according to theoretical
      melting temperature and run under one condition. In conclusion, the MTAW is a
      versatile tool that can facilitate screening of a large number of probes for
      genotyping assays and can also enhance the performance of diagnostic arrays.

PMID- 18063567
TI  - Nuclear RNA export factor 7 is localized in processing bodies and neuronal RNA
      granules through interactions with shuttling hnRNPs.
AB  - The nuclear RNA export factor (NXF) family proteins have been implicated in
      various aspects of post-transcriptional gene expression. This study shows that
      mouse NXF7 exhibits heterologous localization, i.e. NXF7 associates with
      translating ribosomes, stress granules (SGs) and processing bodies (P-bodies),
      the latter two of which are believed to be cytoplasmic sites of storage,
      degradation and/or sorting of mRNAs. By yeast two-hybrid screening, a series of
      heterogeneous nuclear ribonucleoproteins (hnRNPs) were identified as possible
      binding partners for NXF7. Among them, hnRNP A3, which is believed to be involved
      in translational control and/or cytoplasmic localization of certain mRNAs, formed
      a stable complex with NXF7 in vitro. Although hnRNP A3 was not associated with
      translating ribosomes, it was co-localized with NXF7 in P-bodies. After exposing
      to oxidative stress, NXF7 trans-localized to SGs, whereas hnRNP A3 did not. In
      differentiated neuroblastoma Neuro2a cells, NXF7 was co-localized with hnRNP A3
      in cell body and neurites. The amino terminal half of NXF7, which was required
      for stable complex formation with hnRNP A3, coincided with the region required
      for localization in both P-bodies and neuronal RNA granules. These findings
      suggest that NXF7 plays a role in sorting, transport and/or storage of mRNAs
      through interactions with hnRNP A3.

PMID- 18063569
TI  - The yeast ribosome synthesis factor Emg1 is a novel member of the superfamily of
      alpha/beta knot fold methyltransferases.
AB  - Emg1 was previously shown to be required for maturation of the 18S rRNA and
      biogenesis of the 40S ribosomal subunit. Here we report the determination of the
      crystal structure of Emg1 at 2 A resolution in complex with the methyl donor, S
      adenosyl-methionine (SAM). This structure identifies Emg1 as a novel member of
      the alpha/beta knot fold methyltransferase (SPOUT) superfamily. In addition to
      the conserved SPOUT core, Emg1 has two unique domains that form an extended
      surface, which we predict to be involved in binding of RNA substrates. A point
      mutation within a basic patch on this surface almost completely abolished RNA
      binding in vitro. Three point mutations designed to disrupt the interaction of
      Emg1 with SAM each caused>100-fold reduction in SAM binding in vitro. Expression
      of only Emg1 with these mutations could support growth and apparently normal
      ribosome biogenesis in strains genetically depleted of Emg1. We conclude that the
      catalytic activity of Emg1 is not essential and that the presence of the protein
      is both necessary and sufficient for ribosome biogenesis.

PMID- 18063570
TI  - PlantGDB: a resource for comparative plant genomics.
AB  - PlantGDB (http://www.plantgdb.org/) is a genomics database encompassing sequence
      data for green plants (Viridiplantae). PlantGDB provides annotated transcript
      assemblies for >100 plant species, with transcripts mapped to their cognate
      genomic context where available, integrated with a variety of sequence analysis
      tools and web services. For 14 plant species with emerging or complete genome
      sequence, PlantGDB's genome browsers (xGDB) serve as a graphical interface for
      viewing, evaluating and annotating transcript and protein alignments to
      chromosome or bacterial artificial chromosome (BAC)-based genome assemblies.
      Annotation is facilitated by the integrated yrGATE module for community curation
      of gene models. Novel web services at PlantGDB include Tracembler, an iterative
      alignment tool that generates contigs from GenBank trace file data and BioExtract
      Server, a web-based server for executing custom sequence analysis workflows.
      PlantGDB also hosts a plant genomics research outreach portal (PGROP) that
      facilitates access to a large number of resources for research and training.

PMID- 18063571
TI  - Direct quantification of fusion rate reveals a distal role for AS160 in insulin
      stimulated fusion of GLUT4 storage vesicles.
AB  - Insulin-stimulated GLUT4 translocation to the plasma membrane constitutes a key
      process for blood glucose control. However, convenient and robust assays to
      monitor this dynamic process in real time are lacking, which hinders current
      progress toward elucidation of the underlying molecular events as well as screens
      for drugs targeting this particular pathway. Here, we have developed a novel dual
      colored probe to monitor the translocation process of GLUT4 based on dual color
      fluorescence measurement. We demonstrate that this probe is more than an order of
      magnitude more sensitive than the current technology for detecting fusion events
      from single GLUT4 storage vesicles (GSVs). A small fraction of fusion events were
      found to be of the "kiss-and-run" type. For the first time, we show that insulin
      stimulation evokes a approximately 40-fold increase in the fusion of GSVs in 3T3
      L1 adipocytes, compared with basal conditions. The probe can also be used to
      monitor the prefusion behavior of GSVs. By quantifying both the docking and
      fusion rates simultaneously, we demonstrate a proportional inhibition in both
      docking and fusion of GSVs by a dominant negative mutant of AS160, indicating a
      role for AS160 in the docking of GSVs but not in the regulation of GSV fusion
      after docking.

PMID- 18063572
TI  - KLF2 transcription factor modulates blood vessel maturation through smooth muscle
      cell migration.
AB  - Vasculogenesis, angiogenesis, and maturation are three major phases of the
      development of blood vessels. Although many receptors required for blood vessel
      formation have been defined, the intracellular signal transduction pathways
      involved in vascular maturation remain unclear. KLF2(-/-) embryos fail to develop
      beyond 13.5 days because of a lack of blood vessel stabilization. The molecular
      mechanism of KLF2 function in embryonic vascular vessels is still largely
      unknown. Here we show a normal development pattern of endothelial cells in KLF2(
      /-) embryos but a defect of smooth muscle cells at the dorsal side of the aorta.
      This phenotype results from arrested vascular maturation characterized by the
      failure of mural cells to migrate around endothelial cells. This migration defect
      is also observed when platelet-derived growth factor-B (PDGF) controlled
      migration is studied in murine embryonic fibroblast (MEF) cells from KLF2(-/-)
      animals. In addition, KLF2(-/-) MEFs exhibit a significant growth defect,
      indicating that KLF2 is required to maintain the viability of MEF cells. The PDGF
      signal is mediated through the Src signaling pathway, and a downstream target of
      KLF2 is sphingosine 1-phosphate receptor 1. These studies demonstrate that KLF2
      is required for smooth muscle cell migration and elucidate a novel mechanism
      involving communication between PDGF and KLF2 in vascular maturation.

PMID- 18063573
TI  - Sialic acid mutarotation is catalyzed by the Escherichia coli beta-propeller
      protein YjhT.
AB  - The acquisition of host-derived sialic acid is an important virulence factor for
      some bacterial pathogens, but in vivo this sugar acid is sequestered in
      sialoconjugates as the alpha-anomer. In solution, however, sialic acid is present
      mainly as the beta-anomer, formed by a slow spontaneous mutarotation. We studied
      the Escherichia coli protein YjhT as a member of a family of uncharacterized
      proteins present in many sialic acid-utilizing pathogens. This protein is able to
      accelerate the equilibration of the alpha- and beta-anomers of the sialic acid N
      acetylneuraminic acid, thus describing a novel sialic acid mutarotase activity.
      The structure of this periplasmic protein, solved to 1.5A resolution, reveals a
      dimeric 6-bladed unclosed beta-propeller, the first of a bacterial Kelch domain
      protein. Mutagenesis of conserved residues in YjhT demonstrated an important role
      for Glu-209 and Arg-215 in mutarotase activity. We also present data suggesting
      that the ability to utilize alpha-N-acetylneuraminic acid released from complex
      sialoconjugates in vivo provides a physiological advantage to bacteria containing
      YjhT.

PMID- 18063574
TI  - Kinetic rationale for selectivity toward N- and C-terminal oxygen-dependent
      degradation domain substrates mediated by a loop region of hypoxia-inducible
      factor prolyl hydroxylases.
AB  - Hydroxylation of two conserved prolyl residues in the N- and C-terminal oxygen
      dependent degradation domains (NODD and CODD) of the alpha-subunit of hypoxia
      inducible factor (HIF) signals for its degradation via the ubiquitin-proteasome
      pathway. In human cells, three prolyl hydroxylases (PHDs 1-3) belonging to the
      Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenase family catalyze prolyl
      hydroxylation with differing selectivity for CODD and NODD. Sequence analysis of
      the catalytic domains of the PHDs in the light of crystal structures for PHD2,
      and results for other 2OG oxygenases, suggested that either the C-terminal region
      or a loop linking two beta-strands (beta2 and beta3 in human PHD2) are important
      in determining substrate selectivity. Mutation analyses on PHD2 revealed that the
      beta2beta3 loop is a major determinant in conferring selectivity for CODD over
      NODD peptides. A chimeric PHD in which the beta2beta3 loop of PHD2 was replaced
      with that of PHD3 displayed an almost complete selectivity for CODD (in
      competition experiments), as observed for wild-type PHD3. CODD was observed to
      bind much more tightly to this chimeric protein than the wild type PHD2 catalytic
      domain.

PMID- 18063575
TI  - Structural kinetics of cardiac troponin C mutants linked to familial hypertrophic
      and dilated cardiomyopathy in troponin complexes.
AB  - The key events in regulating cardiac muscle contraction involve Ca(2+) binding to
      and release from cTnC (troponin C) and structural changes in cTnC and other thin
      filament proteins triggered by Ca(2+) movement. Single mutations L29Q and G159D
      in human cTnC have been reported to associate with familial hypertrophic and
      dilated cardiomyopathy, respectively. We have examined the effects of these
      individual mutations on structural transitions in the regulatory N-domain of cTnC
      triggered by Ca(2+) binding and dissociation. This study was carried out with a
      double mutant or triple mutants of cTnC, reconstituted into troponin with
      tryptophanless cTnI and cTnT. The double mutant, cTnC(L12W/N51C) labeled with 1,5
      IAEDANS at Cys-51, served as a control to monitor Ca(2+)-induced opening and
      closing of the N-domain by Forster resonance energy transfer (FRET). The triple
      mutants contained both L12W and N51C labeled with 1,5-IAEDANS, and either L29Q or
      G159D. Both mutations had minimal effects on the equilibrium distance between Trp
      12 and Cys-51-AEDANS in the absence or presence of bound Ca(2+). L29Q had no
      effect on the closing rate of the N-domain triggered by release of Ca(2+), but
      reduced the Ca(2+)-induced opening rate. G159D reduced both the closing and
      opening rates. Previous results showed that the closing rate of cTnC N-domain
      triggered by Ca(2+) dissociation was substantially enhanced by PKA
      phosphorylation of cTnI. This rate enhancement was abolished by L29Q or G159D.
      These mutations alter the kinetics of structural transitions in the regulatory N
      domain of cTnC that are involved in either activation (L29Q) or deactivation
      (G159D). Both mutations appear to be antagonistic toward phosphorylation
      signaling between cTnI and cTnC.

PMID- 18063576
TI  - PKR and PKR-like endoplasmic reticulum kinase induce the proteasome-dependent
      degradation of cyclin D1 via a mechanism requiring eukaryotic initiation factor
      2alpha phosphorylation.
AB  - Cyclin D1 plays a critical role in controlling the G(1)/S transition via the
      regulation of cyclin-dependent kinase activity. Several studies have indicated
      that cyclin D1 translation is decreased upon activation of the eukaryotic
      initiation factor 2alpha (eIF2alpha) kinases. We examined the effect of
      activation of the eIF2alpha kinases PKR and PKR-like endoplasmic reticulum kinase
      (PERK) on cyclin D1 protein levels and translation and determined that cyclin D1
      protein levels decrease upon the induction of PKR and PERK catalytic activity but
      that this decrease is not due to translation. Inhibition of the 26 S proteasome
      with MG132 rescued cyclin D1 protein levels, indicating that rather than
      inhibiting translation, PKR and PERK act to increase cyclin D1 degradation.
      Interestingly, this effect still requires eIF2alpha phosphorylation at serine 51,
      as cyclin D1 remains unaffected in cells containing a non-phosphorylatable form
      of the protein. This proteasome-dependent degradation of cyclin D1 requires an
      intact ubiquitination pathway, although the ubiquitination of cyclin D1 is not
      itself affected. Furthermore, this degradation is independent of phosphorylation
      of cyclin D1 at threonine 286, which is mediated by the glycogen synthase kinase
      3beta and mitogen-activated protein kinase pathways as described in previous
      studies. Our study reveals a novel functional cross-talk between eIF2alpha
      phosphorylation and the proteasomal degradation of cyclin D1 and that this
      degradation is dependent upon eIF2alpha phosphorylation during short, but not
      prolonged, periods of stress.

PMID- 18063578
TI  - The layered structure of human mitochondrial DNA nucleoids.
AB  - Mitochondrial DNA (mtDNA) occurs in cells in nucleoids containing several copies
      of the genome. Previous studies have identified proteins associated with these
      large DNA structures when they are biochemically purified by sedimentation and
      immunoaffinity chromatography. In this study, formaldehyde cross-linking was
      performed to determine which nucleoid proteins are in close contact with the
      mtDNA. A set of core nucleoid proteins is found in both native and cross-linked
      nucleoids, including 13 proteins with known roles in mtDNA transactions. Several
      other metabolic proteins and chaperones identified in native nucleoids, including
      ATAD3, were not observed to cross-link to mtDNA. Additional immunofluorescence
      and protease susceptibility studies showed that an N-terminal domain of ATAD3
      previously proposed to bind to the mtDNA D-loop is directed away from the
      mitochondrial matrix, so it is unlikely to interact with mtDNA in vivo. These
      results are discussed in relation to a model for a layered structure of mtDNA
      nucleoids in which replication and transcription occur in the central core,
      whereas translation and complex assembly may occur in the peripheral region.

PMID- 18063577
TI  - Biochemical activities of Arabidopsis RNA-dependent RNA polymerase 6.
AB  - In Arabidopsis, genetic evidence demonstrates that RNA-dependent RNA polymerase 6
      (RDR6) plays a fundamental role in at least four RNA silencing pathways whose
      functions range from defense against transgenes or viruses to endogene regulation
      in development and in stress responses. Despite its critical role in RNA
      silencing, the biochemical activities of RDR6 have yet to be characterized. In
      this study, we transiently expressed Arabidopsis RDR6 in Nicotiana benthamiana
      and investigated the biochemical activities of immunopurified RDR6 in vitro. We
      showed that RDR6 possesses terminal nucleotidyltransferase activity as well as
      primer-independent RNA polymerase activity on single-stranded RNAs. We found that
      RDR6 cannot distinguish RNAs with or without a cap or poly(A) tail. We also
      demonstrated that RDR6 has strong polymerase activity on single-stranded DNA. All
      these activities require the conserved catalytic Asp(867) residue. Our findings
      have important implications on the processes involving RDR6 in vivo and provide
      new biochemical insights into the mechanisms of RNA silencing in Arabidopsis.

PMID- 18063579
TI  - Determinants of anion-proton coupling in mammalian endosomal CLC proteins.
AB  - Many proteins of the CLC gene family are Cl(-) channels, whereas others, like the
      bacterial ecClC-1 or mammalian ClC-4 and -5, mediate Cl(-)/H(+) exchange.
      Mutating a "gating glutamate" (Glu-224 in ClC-4 and Glu-211 in ClC-5) converted
      these exchangers into anion conductances, as did the neutralization of another,
      intracellular "proton glutamate" in ecClC-1. We show here that neutralizing the
      proton glutamate of ClC-4 (Glu-281) and ClC-5 (Glu-268), but not replacing it
      with aspartate, histidine, or tyrosine, rather abolished Cl(-) and H(+)
      transport. Surface expression was unchanged by these mutations. Uncoupled Cl(-)
      transport could be restored in the ClC-4(E281A) and ClC-5(E268A) proton glutamate
      mutations by additionally neutralizing the gating glutamates, suggesting that
      wild type proteins transport anions only when protons are supplied through a
      cytoplasmic H(+) donor. Each monomeric unit of the dimeric protein was found to
      be able to carry out Cl(-)/H(+) exchange independently from the transport
      activity of the neighboring subunit. NO(3)(-) or SCN(-) transport was partially
      uncoupled from H(+) countertransport but still depended on the proton glutamate.
      Inserting proton glutamates into CLC channels altered their gating but failed to
      convert them into Cl(-)/H(+) exchangers. Noise analysis indicated that ClC-5
      switches between silent and transporting states with an apparent unitary
      conductance of 0.5 picosiemens. Our results are consistent with the idea that Cl(
      )/H(+) exchange of the endosomal ClC-4 and -5 proteins relies on proton delivery
      from an intracellular titratable residue at position 268 (numbering of ClC-5) and
      that the strong rectification of currents arises from the voltage-dependent
      proton transfer from Glu-268 to Glu-211.

PMID- 18063580
TI  - Tom20 and Tom22 share the common signal recognition pathway in mitochondrial
      protein import.
AB  - Precise targeting of mitochondrial precursor proteins to mitochondria requires
      receptor functions of Tom20, Tom22, and Tom70 on the mitochondrial surface. Tom20
      is a major import receptor that recognizes preferentially mitochondrial
      presequences, and Tom70 is a specialized receptor that recognizes presequence
      less inner membrane proteins. The cytosolic domain of Tom22 appears to function
      as a receptor in cooperation with Tom20, but how its substrate specificity
      differs from that of Tom20 remains unclear. To reveal possible differences in
      substrate specificities between Tom20 and Tom22, if any, we deleted the receptor
      domain of Tom20 or Tom22 in mitochondria in vitro by introducing cleavage sites
      for a tobacco etch virus protease between the receptor domains and transmembrane
      segments of Tom20 and Tom22. Then mitochondria without the receptor domain of
      Tom20 or Tom22 were analyzed for their abilities to import various mitochondrial
      precursor proteins targeted to different mitochondrial subcompartments in vitro.
      The effects of deletion of the receptor domains on the import of different
      mitochondrial proteins for different import pathways were quite similar between
      Tom20 and Tom22. Therefore Tom20 and Tom22 are apparently involved in the same
      step or sequential steps along the same pathway of targeting signal recognition
      in import.

PMID- 18063581
TI  - AMP-activated protein kinase phosphorylates Golgi-specific brefeldin A resistance
      factor 1 at Thr1337 to induce disassembly of Golgi apparatus.
AB  - Sufficiency and depletion of nutrients regulate the cellular activities through
      the protein phosphorylation reaction; however, many protein substrates remain to
      be clarified. GBF1 (Golgi-specific brefeldin A resistance factor 1), a guanine
      nucleotide exchange factor for the ADP-ribosylation factor family associated with
      the Golgi apparatus, was isolated as a phosphoprotein from the glucose-depleted
      cells by using the phospho-Akt-substrate antibody, which recognizes the substrate
      proteins of several protein kinases. The phosphorylation of GBF1 was induced by 2
      deoxyglucose (2-DG), which blocks glucose utilization and increases the
      intracellular AMP concentration, and by AICAR, an AMP-activated protein kinase
      (AMPK) activator. This phosphorylation was observed in the cells expressing the
      constitutively active AMPK. The 2-DG-induced phosphorylation of GBF1 was
      suppressed by Compound C, an AMPK inhibitor, and by the overexpression of the
      kinase-negative AMPK. Analysis using the deletion and point mutants identified
      Thr(1337) as the 2-DG-induced phosphorylation site in GBF1, which is
      phosphorylated by AMPK in vitro. ATP depletion is known to provoke the Golgi
      apparatus disassembly. Immunofluorescent microscopic analysis with the Golgi
      markers indicated that GBF1 associates with the fragmented Golgi apparatus in the
      cells treated with 2-DG and AICAR. The expression of the kinase-negative AMPK and
      the GBF1 mutant replacing Thr(1337) by Ala prevented the 2-DG-induced Golgi
      disassembly. These results indicate that GBF1 is a novel AMPK substrate and that
      the AMPK-mediated phosphorylation of GBF1 at Thr(1337) has a critical role,
      presumably by attenuating the function of GBF1, in the disassembly of the Golgi
      apparatus induced under stress conditions that lower the intracellular ATP
      concentration.

PMID- 18063582
TI  - PINCH-1 regulates the ERK-Bim pathway and contributes to apoptosis resistance in
      cancer cells.
AB  - Resistance to apoptosis is a hallmark of cancer cells. We report here that PINCH
      1, a cytoplasmic component of cell-extracellular matrix adhesions, is required
      for protection of multiple types of cancer cells from apoptosis. Furthermore,
      using HT-1080 fibrosarcoma cells as a model system, we have investigated the
      signaling pathway through which PINCH-1 contributes to apoptosis resistance. Loss
      of PINCH-1 markedly increases the level of Bim and promotes Bim translocation to
      mitochondria, resulting in activation of the intrinsic apoptosis pathway.
      Depletion of Bim completely blocked apoptosis induced by the loss of PINCH-1.
      Thus, PINCH-1 contributes to apoptosis resistance through suppression of Bim.
      Mechanistically, PINCH-1 suppresses Bim not only transcriptionally but also post
      transcriptionally. PINCH-1 promotes activating phosphorylation of Src family
      kinase and ERK1/2. Consistent with this, ERK1/2-mediated Ser(69) phosphorylation
      of Bim, a key signal for turnover of Bim, is suppressed by the removal of PINCH
      1. Our results demonstrate a strong dependence of multiple types of apoptosis
      resistant cancer cells on PINCH-1 and provide new insights into the molecular
      mechanism by which cancer cells are protected from apoptosis.

PMID- 18063583
TI  - Crystal structure of the human laminin receptor precursor.
AB  - The human laminin receptor (LamR) interacts with many ligands, including laminin,
      prions, Sindbis virus, and the polyphenol (-)-epigallocatechin-3-gallate (EGCG),
      and has been implicated in a number of diseases. LamR is overexpressed on tumor
      cells, and targeting LamR elicits anti-cancer effects. Here, we report the
      crystal structure of human LamR, which provides insights into its function and
      should facilitate the design of novel therapeutics targeting LamR.

PMID- 18063584
TI  - Epac, in synergy with cAMP-dependent protein kinase (PKA), is required for cAMP
      mediated mitogenesis.
AB  - cAMP stimulates proliferation in many cell types. For many years, cAMP-dependent
      protein kinase (PKA) represented the only known cAMP effector. PKA, however, does
      not fully mimic the action of cAMP, indicating the existence of a PKA-independent
      component. Since cAMP-mediated activation of the G-protein Rap1 and its
      phosphorylation by PKA are strictly required for the effects of cAMP on
      mitogenesis, we hypothesized that the Rap1 activator Epac might represent the PKA
      independent factor. Here we report that Epac acts synergistically with PKA in
      cAMP-mediated mitogenesis. We have generated a new dominant negative Epac mutant
      that revealed that activation of Epac is required for thyroid-stimulating hormone
      or cAMP stimulation of DNA synthesis. We demonstrate that Epac's action on cAMP
      mediated activation of Rap1 and cAMP-mediated mitogenesis depends on the
      subcellular localization of Epac via its DEP domain. Disruption of the DEP
      dependent subcellular targeting of Epac abolished cAMP-Epac-mediated Rap1
      activation and thyroid-stimulating hormone-mediated cell proliferation,
      indicating that an Epac-Rap-PKA signaling unit is critical for the mitogenic
      action of cAMP.

PMID- 18063585
TI  - Substrate orientation in xanthine oxidase: crystal structure of enzyme in
      reaction with 2-hydroxy-6-methylpurine.
AB  - Xanthine oxidoreductase catalyzes the final two steps of purine catabolism and is
      involved in a variety of pathological states ranging from hyperuricemia to
      ischemia-reperfusion injury. The human enzyme is expressed primarily in its
      dehydrogenase form utilizing NAD+ as the final electron acceptor from the
      enzyme's flavin site but can exist as an oxidase that utilizes O2 for this
      purpose. Central to an understanding of the enzyme's function is knowledge of
      purine substrate orientation in the enzyme's molybdenum-containing active site.
      We report here the crystal structure of xanthine oxidase, trapped at the stage of
      a critical intermediate in the course of reaction with the slow substrate 2
      hydroxy-6-methylpurine at 2.3A. This is the first crystal structure of a reaction
      intermediate with a purine substrate that is hydroxylated at its C8 position as
      is xanthine and confirms the structure predicted to occur in the course of the
      presently favored reaction mechanism. The structure also corroborates recent work
      suggesting that 2-hydroxy-6-methylpurine orients in the active site with its C2
      carbonyl group interacting with Arg-880 and extends our hypothesis that xanthine
      binds opposite this orientation, with its C6 carbonyl positioned to interact with
      Arg-880 in stabilizing the MoV transition state.

PMID- 18063586
TI  - Rhodopsin and 9-demethyl-retinal analog: effect of a partial agonist on
      displacement of transmembrane helix 6 in class A G protein-coupled receptors.
AB  - Rhodopsin is the visual pigment of rod cells and a prototypical G protein-coupled
      receptor. It is activated by cis-->trans photoisomerization of the covalently
      bound chromophore 11-cis-retinal, which acts in the cis configuration as an
      inverse agonist. Light-induced formation of the full agonist all-trans-retinal in
      situ triggers conformational changes in the protein moiety. Partial agonists of
      rhodopsin include a retinal analog lacking the methyl group at C-9, termed 9
      demethyl-retinal (9-dm-retinal). Rhodopsin reconstituted with this retinal (9-dm
      rhodopsin) activates G protein poorly. Here we investigated the molecular nature
      of the partial agonism in 9-dm-rhodopsin using site-directed spin labeling.
      Earlier site-directed spin labeling studies of rhodopsin identified a rigid-body
      tilt of the cytoplasmic segment of [corrected] transmembrane helix 6 (TM6) by
      approximately 6A as a central event in rhodopsin activation. Data presented here
      provide additional evidence for this mechanism. Only a small fraction of
      photoexcited 9-dm pigments reaches the TM6-tilted conformation. This fraction can
      be increased by increasing proton concentration or [corrected] by anticipation of
      the activating protonation step by the mutation E134Q in 9-dm-rhodopsin. These
      results on protein conformation are in complete accord with previous findings
      regarding the biological activity of the 9-dm pigments. When the proton
      concentration is further increased, a new state arises in 9-dm pigments that is
      linked to direct proton uptake at the retinal Schiff base. This state apparently
      has a conformation distinguishable from the active state.

PMID- 18063587
TI  - Seizure outcome after resective epilepsy surgery in patients with low IQ.
AB  - Epilepsy surgery has been questioned for patients with low IQ, since a low
      cognitive level is taken to indicate a widespread disturbance of cerebral
      function with unsatisfactory prognosis following resective surgery. The
      prevalence of epilepsy in patients with cognitive dysfunction is, however, higher
      than in the general population and the epilepsy is often more severe and
      difficult to treat. It is therefore important to try to clarify whether IQ
      predicts seizure outcome after resective epilepsy surgery. The Swedish National
      Epilepsy Surgery Register, which includes data on all epilepsy surgery procedures
      in Sweden since 1990, was analysed for all resective procedures performed 1990
      99. Sustained seizure freedom with or without aura at the 2-year follow-up was
      analysed as a function of pre-operative IQ level categorized as IQ <50, IQ 50-69
      and IQ >or=70 and was also adjusted for the following variables: age at epilepsy
      onset, age at surgery, pre-operative seizure frequency, pre-operative
      neurological impairment, resection type and histopathological diagnosis. Four
      hundred and forty-eight patients underwent resective epilepsy surgery in Sweden
      from 1990 to 1999 and completed the 2-year follow-up: 72 (16%) had IQ <70, (18
      with IQ <50 and 54 with IQ 50-69) and 376 IQ >or=70. There were 313 adults and
      135 children <or=18 years. Three hundred and twenty-five patients underwent
      temporal lobe resections (TLR) and 123 underwent various extratemporal resections
      (XTLR). At the 2-year follow-up, 56% (252/448) of the patients were seizure free:
      22% (4/18) in the IQ <50 group, 37% (20/54) in the IQ 50-69 group and 61%
      (228/376) in the IQ >or=70 group. There was a significant relation between IQ
      category and seizure freedom [odds ratio (OR) 0.41, 95% confidence interval (CI)
      0.27-0.62] and this held also when adjusting for clinical variables [OR 0.58 (95%
      CI 0.35-0.95)]. In this population-based epilepsy surgery series, IQ level was
      shown to be an independent predictor of seizure freedom at the 2-year follow-up.
      However, many of the low-IQ patients benefit from surgery, especially patients
      with lesions. Low IQ should not exclude patients from resective epilepsy surgery,
      but is an important prognostic factor to consider in the counselling process.

PMID- 18063588
TI  - Direct voxel-based comparison between grey matter hypometabolism and atrophy in
      Alzheimer's disease.
AB  - Although the patterns of structural and metabolic brain alterations in
      Alzheimer's disease are being refined and discrepancies between them are being
      underlined, the exact relationships between atrophy and hypometabolism are still
      unclear. In this study, we aimed to provide a direct comparison between grey
      matter atrophy and hypometabolism in a sample of patients with clinically
      probable Alzheimer's disease, using a voxel-based method specially designed to
      statistically compare the two imaging modalities. Eighteen patients with probable
      Alzheimer's disease of mild severity and 15 healthy aged controls underwent both
      high-resolution T1 MRI and resting-state (18)FDG-PET. The MRI data sets were
      handled using optimized VBM. The PET data were coregistered to their
      corresponding MRI, corrected voxel-wise for partial volume averaging and
      spatially normalized using the same parameters as those of their corresponding
      MRI volume. A differential smoothing was applied on the MRI and PET data sets to
      equalize their effective smoothness and resolution. For each patient, Z-score
      maps of atrophy and hypometabolism were created by comparing to the controls data
      set, respectively averaged to provide the profile of hypometabolism and atrophy,
      and entered in a voxel-by-voxel SPM analysis to assess the statistical
      differences between hypometabolism and atrophy. The observed patterns of
      hypometabolism and atrophy were consistent with previous studies. However, the
      direct comparison revealed marked regional variability in the relationship
      between hypometabolism and atrophy. Thus, the hypometabolism significantly
      exceeded atrophy in most altered structures, particularly in the posterior
      cingulate-precuneus, orbitofrontal, inferior temporo-parietal, parahippocampal,
      angular and fusiform areas. In contrast, a few hypometabolic structures among
      which the hippocampus exhibited similar degrees of atrophy and hypometabolism, a
      profile that significantly differed from the posterior cingulate. Excessive
      hypometabolism relative to atrophy suggests the intervention of additional
      hypometabolism-inducing factors, such as disconnection and amyloid deposition,
      resulting in genuine functional perturbation ahead of actual atrophy and perhaps
      of pathology as well. Conversely, in the hippocampus, where disconnection
      processes are also likely to occur, relative synaptic compensatory mechanisms may
      be taking place, maintaining neuronal activity in the face of structural
      alterations.

PMID- 18063589
TI  - ROCK inhibition and CNTF interact on intrinsic signalling pathways and
      differentially regulate survival and regeneration in retinal ganglion cells.
AB  - Functional regeneration in the CNS is limited by lesion-induced neuronal
      apoptosis and an environment inhibiting axonal elongation. A principal, yet
      unresolved question is the interaction between these two major factors. We thus
      evaluated the role of pharmacological inhibition of rho kinase (ROCK), a key
      mediator of myelin-derived axonal growth inhibition and CNTF, a potent
      neurotrophic factor for retinal ganglion cells (RGC), in models of retinal
      ganglion cell apoptosis and neurite outgrowth/regeneration in vitro and in vivo.
      Here, we show for the first time that the ROCK inhibitor Y-27632 significantly
      enhanced survival of RGC in vitro and in vivo. In vitro, the co-application of
      CNTF and Y-27632 potentiated the effect of either substance alone. ROCK
      inhibition resulted in the activation of the intrinsic MAPK pathway, and the
      combination of CNTF and Y-27632 resulted in even more pronounced MAPK activation.
      While CNTF also induced STAT3 phosphorylation, the additional application of ROCK
      inhibitor surprisingly diminished the effects of CNTF on STAT3 phosphorylation.
      ROCK activity was also decreased in an additive manner by both substances. In
      vivo, both CNTF and Y-27632 enhanced regeneration of RGC into the non-permissive
      optic nerve crush model and additive effects were observed after combination
      treatment. Further evaluation using specific inhibitors delineate STAT3 as a
      negative regulator of neurite growth and positive regulator of cell survival,
      while MAPK and Akt support neurite growth. These results show that next to
      neurotrophic factors ROCK inhibition by Y-27632 potently supports survival of
      lesioned adult CNS neurons. Co-administration of CNTF and Y-27632 results in
      additive effects on neurite outgrowth and regeneration. The interaction of
      intracellular signalling pathways may, however, attenuate more pronounced synergy
      and has to be taken into account for future treatment strategies.

PMID- 18063590
TI  - Exposure-response of silicosis mortality in Swedish iron ore miners.
AB  - OBJECTIVES: To assess the exposure-response relationship between exposure to
      quartz and fatal silicosis. METHODS: The mortality from silicosis in 7729 miners
      was analyzed and compared to their estimated exposure to respirable quartz. The
      miners had been working as a miner for at least 1 year between 1923 and 1996.
      Their mortality between 1952 and 2001 was studied by using information from the
      national cause of death register. Both underlying and contributing causes of
      death were considered in the analysis. The exposure to quartz was estimated from
      job titles and using 3239 measurements of personal exposure to respirable quartz
      from 1965 to 1999. The mortality rates were adjusted to attained age and years of
      birth using a Poisson regression. RESULTS: The median cumulative exposure among
      the 7729 miners was 0.9 mg x years m(-3). There were 58 deaths from silicosis.
      Their median cumulative exposure was 4.8 mg x years m(-3). The crude mortality
      rate was 53 cases per 100,000 person-years with an exposure-response
      relationship. CONCLUSION: There seems to be an increased risk of fatal silicosis
      at exposure levels around 3 mg x years m(-3) for respirable quartz.

PMID- 18063591
TI  - Cellular phone use and risk of benign and malignant parotid gland tumors--a
      nationwide case-control study.
AB  - The objective of this nationwide study was to assess the association between
      cellular phone use and development of parotid gland tumors (PGTs). The methods
      were based on the international INTERPHONE study that aimed to evaluate possible
      adverse effects of cellular phone use. The study included 402 benign and 58
      malignant incident cases of PGTs diagnosed in Israel at age 18 years or more, in
      2001-2003, and 1,266 population individually matched controls. For the entire
      group, no increased risk of PGTs was observed for ever having been a regular
      cellular phone user (odds ratio = 0.87; p = 0.3) or for any other measure of
      exposure investigated. However, analysis restricted to regular users or to
      conditions that may yield higher levels of exposure (e.g., heavy use in rural
      areas) showed consistently elevated risks. For ipsilateral use, the odds ratios
      in the highest category of cumulative number of calls and call time without use
      of hands-free devices were 1.58 (95% confidence interval: 1.11, 2.24) and 1.49
      (95% confidence interval: 1.05, 2.13), respectively. The risk for contralateral
      use was not significantly different from 1. A positive dose-response trend was
      found for these measurements. Based on the largest number of benign PGT patients
      reported to date, our results suggest an association between cellular phone use
      and PGTs.

PMID- 18063593
TI  - Recreational drug use: a major risk factor for gastroschisis?
AB  - The authors tested the hypothesis that the birth prevalence of gastroschisis is
      positively associated with use of recreational drugs in early pregnancy. A
      matched case-control study was carried out in three regions of the United Kingdom
      over the period January 2001 through August 2003. For each case, three liveborn
      controls were matched by initial intended place of delivery, region, and maternal
      age. Maternal hair analysis provided independent verification of recreational
      drug use. Conditional logistic regression was used to estimate mutually adjusted
      odds ratios. Estimates were revised using data from hair analysis. Statistically
      significant adjusted odds ratios for gastroschisis were associated with first
      trimester use of 1) any recreational drug (odds ratio (OR) = 2.2, 95% confidence
      interval (CI): 1.2, 4.3) and 2) vasoconstrictive recreational drugs (defined as
      cocaine, amphetamines, and ecstasy) (OR = 3.3, 95% CI: 1.0, 10.5). Other
      significant exposures included aspirin use (OR = 20.4, 95% CI: 2.2, 191.5),
      cigarette smoking (OR = 1.7, 95% CI: 1.1, 2.6), and prior history of gynecologic
      infection/disease (OR = 2.6, 95% CI: 1.2, 5.6). Recreational drug use is a
      significant risk factor for gastroschisis and is one of a constellation of
      potentially preventable exposures which include cigarette smoking, aspirin use,
      and history of gynecologic infection/disease. Maternal hair analysis proved an
      acceptable and valuable method of independently verifying recreational drug use.

PMID- 18063592
TI  - Dietary fiber, lung function, and chronic obstructive pulmonary disease in the
      atherosclerosis risk in communities study.
AB  - Recent data suggest beneficial effects of fiber intake on chronic respiratory
      symptoms in adults that are independent of antioxidant vitamin intake, but little
      is known about fiber consumption in relation to lung function and chronic
      obstructive pulmonary disease (COPD). The authors investigated the association of
      fiber intake with lung function and COPD in 11,897 US men and women from the
      Atherosclerosis Risk in Communities study (1987-1989). After control for
      potential confounders, positive associations were found between lung function and
      fiber intake from all sources as well as from cereal or fruit alone. Compared
      with those in the lowest quintile, participants in the highest quintile of total
      fiber intake had a 60.2-ml higher forced expiratory volume in 1 second (FEV(1))
      (p for trend < 0.001), 55.2-ml higher forced vital capacity (FVC) (p = 0.001),
      0.4% higher FEV(1)/FVC ratio (p = 0.040), 1.8% higher percent predicted FEV(1) (p
      < 0.001), and 1.4% higher percent predicted FVC (p = 0.001). Adjusted odds ratios
      of COPD for the highest versus lowest quintiles of intake were 0.85 (p = 0.044)
      for total fiber, 0.83 (p = 0.021) for cereal fiber, and 0.72 (p = 0.005) for
      fruit fiber. This study provides the first known evidence that dietary fiber is
      independently associated with better lung function and reduced prevalence of
      COPD.

PMID- 18063594
TI  - Rosuvastatin increases vascular endothelial PPARgamma expression and corrects
      blood pressure variability in obese dyslipidaemic mice.
AB  - AIMS: Statins improve atherosclerotic diseases through cholesterol-reducing
      effects. Whether the latter exclusively mediate similar benefits, e.g. on
      hypertension, in the metabolic syndrome is unclear. We examined the effects of
      rosuvastatin on the components of this syndrome, as reproduced in mice doubly
      deficient in LDL receptors and leptin (DKO). METHODS AND RESULTS: DKO received
      rosuvastatin (10 mg/kg/day or 20 mg/kg/day) or saline for 12 weeks. Saline
      treated DKO mice had elevated blood pressure (BP) and nitric oxide-sensitive BP
      variability recorded by telemetry. Compared with saline, rosuvastatin (20
      mg/kg/day) had no effect on weight gain and a minor effect on plasma cholesterol.
      Despite incomplete correction of insulin sensitivity, rosuvastatin fully
      corrected BP and its variability (P = 0.01), in conjunction with upregulation of
      PPARgamma (but not PPARalpha) in the aortic arch. Rosuvastatin similarly
      increased PPARgamma (P = 0.002) and SOD1 (P = 0.01) expression in isolated
      endothelial cells. Both GW9662, a PPARgamma-specific antagonist, and siRNA raised
      against PPARgamma abrogated rosuvastatin's effect, which was reproduced in
      PPARgamma- (but not PPARalpha-) dependent transactivation assays. CONCLUSION:
      Beyond partial improvement in insulin sensitivity, rosuvastatin normalized BP
      homeostasis in obese dyslipidaemic mice independently of changes in body weight
      or plasma cholesterol. Upregulation of PPARgamma and SOD1 in the endothelium may
      be involved as a unique vasculoprotective effect of statin treatment.

PMID- 18063595
TI  - The additive prognostic value of wall motion abnormalities and coronary flow
      reserve during dipyridamole stress echo.
AB  - AIMS: The aim of the study was to evaluate the prognostic value of Doppler
      echocardiographic-derived coronary flow reserve (CFR) over regional wall motion
      in patients with known or suspected coronary artery disease (CAD) undergoing
      dipyridamole echocardiography test (DET). METHODS AND RESULTS: In a prospective,
      multicentre, observational study, we evaluated 1145 patients (702 males; 64 +/-
      11 years) who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress
      echo with CFR evaluation of LAD by Doppler. DET was positive for regional wall
      motion abnormalities in 291 (25%) and negative in 854 (74%) patients. Mean CFR
      was 2.2 +/- 0.5. At individual patient analysis 702 patients had normal (CFR >
      2.0) and 443 had abnormal CFR on LAD. During a median follow-up of 27 months, 109
      events occurred: 16 deaths, 17 non-fatal myocardial infarctions, 76 re
      hospitalizations for unstable angina. The 30 months infarction-free survival
      showed the best outcome for those patients with negative DET by wall motion
      criteria and normal CFR and the worst outcome for patients with positive DET by
      wall motion and abnormal CFR (99 vs. 68%, P < 0.001). At multivariable analysis,
      CFR on LAD [hazard ratio (HR) 2.4, 95% CI 1.1-5.4, P = 0.030], medical therapy at
      time of testing (HR 2.8, 95% CI 1.2-6.6, P = 0.022), DET positivity for regional
      wall motion abnormalities (HR 3.6, 95% CI 1.5-8.7, P = 0.000), and angina on
      effort (HR 6.3, 95% CI 2.7-14.8, P = 0.000) were independent prognostic
      predictors of hard cardiac events. CONCLUSION: In patients with known or
      suspected CAD, DET result by wall motion criteria and CFR are additive and
      complementary for the identification of patients at risk of experiencing hard
      events.

PMID- 18063596
TI  - Recent respiratory infection and risk of cardiovascular disease: case-control
      study through a general practice database.
AB  - AIMS: Respiratory infection may be associated with an increased risk of major
      cardiovascular events. This case-control study describes associations with these
      events of respiratory infection. METHODS AND RESULTS: The IMS Disease Analyzer
      Mediplus primary care database was used to identify all cases of first-time
      diagnosis of myocardial infarction (MI) or stroke and single matched controls.
      Details were extracted on visits for respiratory infection over the preceding
      year. A total of 11 155 MI cases and 9208 stroke cases were identified. For MI
      and stroke respectively, there were 326 and 260 respiratory infections during the
      month preceding the index date. There was strong evidence of an increased risk of
      both events in the 7 days following infection, for MI adjusted odds ratio (OR)
      2.10 (95% confidence interval 1.38-3.21), for stroke OR 1.92 (95% confidence
      interval 1.24-2.97). The strength of these associations fell over time. The
      associations for MI occurred at all levels of initial underlying cardiovascular
      risk. CONCLUSIONS: There are strong associations between recent respiratory
      infection and major cardiovascular events, for MI at all levels of underlying
      risk. The benefits of reducing respiratory infection either through immunization
      or treating or preventing infection may be substantial.

PMID- 18063597
TI  - Alcohol consumption, TaqIB polymorphism of cholesteryl ester transfer protein,
      high-density lipoprotein cholesterol, and risk of coronary heart disease in men
      and women.
AB  - AIMS: To investigate whether a common polymorphism in the cholesteryl ester
      transfer protein (CETP) gene modifies the relationship of alcohol intake with
      high-density lipoprotein cholesterol (HDL-C) and risk of coronary heart disease
      (CHD). METHODS AND RESULTS: Parallel nested case-control studies among women
      [Nurses' Health Study (NHS)] and men [Health Professionals Follow-up Study
      (HPFS)] where 246 women and 259 men who developed incident CHD were matched to
      controls (1:2) on age and smoking. The TaqIB variant and alcohol consumption were
      associated with higher HDL-C, with the most pronounced effects of alcohol among
      B2 carriers. In the NHS we did not find an inverse association between alcohol
      and CHD in B2 non-carriers (P trend: 0.5), but did among B2 carriers (P trend
      <0.01). Among non-carriers the odds ratio (OR) for CHD among women with an intake
      of 5-14 g/day was 1.4 (95% CI: 0.6-3.7) compared with non-drinkers, whereas among
      B2 carriers the OR was 0.4 (0.2-0.8). Results in men were less suggestive of an
      interaction; corresponding OR's were 1.9 (0.8-4.5) and 0.9 (0.5-1.6), for B2 non
      carriers and carriers, respectively. CONCLUSIONS: The association of alcohol with
      HDL-C levels was modified by CETP TaqIB2 carrier status, and there was also a
      suggestion of a gene-environment interaction on the risk of CHD.

PMID- 18063598
TI  - Impact of antiretroviral therapy on viral tropism in HIV-infected patients
      followed longitudinally for over 5 years.
AB  - BACKGROUND: Viral tropism plays a major role in HIV pathogenesis and may
      influence the activity of entry inhibitors. The impact of antiretroviral therapy
      use on the dynamics of viral tropism over time is still poorly understood.
      PATIENTS AND METHODS: HIV co-receptor usage was determined longitudinally for
      over 5 years in 237 plasma specimens collected from 73 distinct HIV-1-infected
      drug-naive individuals, 42 of whom initiated antiretroviral therapy thereafter
      and 31 who remained untreated. Viral tropism was estimated genotypically using
      the phenotype predictor software webPSSM, considering as X4 virus populations
      those with pure X4 and dual/mixed X4/R5 variants. RESULTS: At baseline, the
      prevalence of X4 viruses was 3.2% and 14.6% in patients who remained untreated
      and in those who initiated antiretroviral therapy, respectively (P = 0.112). Mean
      plasma HIV-RNA was lower in the former compared with the latter (3.8 +/- 0.9
      versus 4.5 +/- 0.9 log; P < 0.004), while conversely the mean CD4 count was
      greater in untreated than in those who had begun therapy (536 +/- 191 versus 278
      +/- 192 cells/mm3; P < 0.001). During follow-up, switch in co-receptor use
      occurred overall in 26% of the study population, with no significant differences
      between the groups. Emergence of X4 viruses was significantly associated with
      lower CD4 counts regardless of antiretroviral treatment exposure. CONCLUSIONS:
      The use of antiretroviral therapy does not seem to influence the selection of X4
      viruses, which mainly occur in patients with low CD4 counts.

PMID- 18063599
TI  - Issues in antifungal susceptibility testing.
AB  - In line with the availability of an increasing array of systemic antifungal
      agents, there is a need for accurate, reproducible and predictive susceptibility
      testing of fungal isolates in order to help inform clinical choice. Much early
      attention on antifungal susceptibility testing focused on defining test
      parameters that produced reproducible and reliable intra- and inter-laboratory
      results and there are now standardized methods for the testing of yeast and mould
      isolates. The application of this standardized approach produces susceptibility
      results that are comparable between laboratories and allow epidemiological
      analyses at the national and even international level. In addition, monitoring
      and prediction of emerging susceptibility trends are now possible. As methodology
      improved, attention shifted to clinical outcome data in order to establish
      breakpoints for antifungal agents. However, there are a large number of
      confounding factors that must be considered when trying to assess the in vivo
      activity of antifungal agents in invasive disease. An approach based on defining
      normal susceptibility ranges, together with pharmacokinetic and pharmacodynamic
      analyses and identification of resistance mechanisms, has helped to establish
      breakpoint data for at least some of the systemic agents active against yeast
      isolates. Moreover, for some drugs, there is a supporting in vitro-in vivo
      correlation available from studies of clinical efficacy. Application of
      susceptibility testing has helped to define the spectrum of activity of all the
      currently available antifungal agents. Both intrinsic and emergent antifungal
      drug resistance are encountered and the predictability of innate resistance has
      meant that species identification is often sufficient to alert the clinician to
      the likelihood of in vitro and often-associated in vivo resistance. Currently,
      emergence of resistance in a previously susceptible strain during a course of
      treatment remains rare.

PMID- 18063600
TI  - New and emerging treatments for fungal infections.
AB  - Although several new antifungal drugs have been licensed in the last 5 years,
      some patients remain difficult to treat. The main reasons for this include
      intrinsic or acquired antifungal resistance, organ dysfunction preventing the use
      of some agents and drug interactions. In addition, some drugs penetrate poorly
      into sanctuary sites including eye and urine, and others are associated with
      considerable adverse events. Here, we review the preclinical and clinical
      development progress with four new antifungal agents: isavuconazole,
      ravuconazole, albaconazole and aminocandin. Isavuconazole and ravuconazole are
      extremely similar, with a broad spectrum of activity, a very long half-life and
      large volume of distribution and good in vivo data supporting their efficacy in
      invasive aspergillosis and candidosis. Both compounds are in early Phase 3
      development. Albaconazole has also shown very potent activity against species of
      Candida, Cryptococcus and Aspergillus. It was well tolerated and effective in
      women with vaginal candidosis. Aminocandin is an intravenous-only echinocandin
      with in vivo activity against Candida spp. and Aspergillus spp. Its extended half
      life probably permits dosing less frequently than once a day. Overall these new
      antifungal agents in development offer extended half-lives, possibly reduced drug
      interaction profiles and good tolerance. Their antifungal spectrum is narrower
      than posaconazole and probably similar to voriconazole (isavuconazole and
      ravuconazole) and caspofungin (aminocandin). Licensure and determination of their
      place in clinical practice requires randomized clinical studies, which are or
      will be underway.

PMID- 18063601
TI  - Early diagnosis of fungal infection in immunocompromised patients.
AB  - Techniques for the diagnosis of invasive fungal infection, including antigen
      testing, nucleic acid detection and radiological imaging, have improved greatly
      in recent years. They have the potential to impact on patient management through
      replacing empirical antifungal strategies with targeted and pre-emptive therapy.
      Factors that influence performance of these diagnostic tests include underlying
      disease, the prevalence of fungal infection in particular populations and
      prophylactic antifungal drug strategies. Understanding these factors is necessary
      for rational use of antifungal agents and optimal management and prevention of
      fungal infection in immunosuppressed patients.

PMID- 18063602
TI  - Management of candidiasis in the intensive care unit.
AB  - In the last two decades, Candida has emerged as an important opportunistic
      pathogen. Patients admitted to the intensive care unit (ICU) are particularly
      susceptible to this infection because of the severity of their underlying illness
      and the excess use of medical and surgical interventions. The frequent use of
      antibiotics, central venous catheters and other intravascular devices as well as
      poor gut motility or abdominal surgery place these patients at high risk of
      infection, which contributes to the morbidity and mortality of the already
      critically ill patient. Early recognition and appropriate management of invasive
      candidiasis are therefore important. This article addresses important management
      issues such as the role of screening for Candida colonization, the use of
      prophylaxis and the choice of antifungal agents for the treatment of presumed and
      proven invasive candidiasis in the adult ICU setting.

PMID- 18063603
TI  - Treatment of zygomycosis: current and new options.
AB  - Zygomycosis is a frequently lethal invasive infection in high-risk patients such
      as the immunocompromised [especially haematopoietic stem cell transplant (HSCT)
      recipients] and patients with type 2 diabetes mellitus. However, zygomycosis has
      also been reported in individuals without known risk factors. The causative fungi
      are members of the order Mucorales and individual species within this group
      require a high level of laboratory skill for their identification. These
      organisms are resistant to voriconazole and also to the echinocandins, and
      although zygomycosis is less commonly documented than invasive aspergillosis in
      leukaemic and HSCT patients, there are recent reports suggesting that it has
      increased in incidence since the introduction of voriconazole. Zygomycosis can
      present clinically as rhinocerebral, pulmonary or disseminated disease which
      progresses rapidly. The management of cases is based on early diagnosis, surgical
      debridement when possible and aggressive antifungal therapy. Based on clinical
      experience, but without the benefit of comparative studies, liposomal
      amphotericin B has become the therapeutic agent of choice. Posaconazole is a new
      orally administered triazole antifungal and the first member of this class to
      have comparable in vitro activity to amphotericin B against most zygomycetes.
      Studies of salvage therapy of zygomycosis with posaconazole have yielded
      promising results and there are additional case reports of successful outcomes
      using these and other antifungal drugs as combination therapy. Adjunctive
      approaches that are showing promise but with limited clinical experience are iron
      chelation and immunotherapy.

PMID- 18063604
TI  - Salvage therapy for invasive aspergillosis.
AB  - Invasive aspergillosis (IA) makes a marked contribution to the mortality of
      immunocompromised hosts, especially those who have received cytotoxic
      chemotherapy for haematological malignancy or allogeneic haemopoietic stem cell
      transplantation. Salvage therapy, in the case of invasive fungal infection,
      generally refers to the treatment of infected individuals who are refractory or
      intolerant to initial therapy administered for at least 7 days. Although clinical
      trials of salvage therapy of IA have been undertaken, most were non-comparator
      studies or contained a non-randomized control group, and criteria for patient
      enrollment and the methods used to assess response were variable. Salvage therapy
      has produced relatively disappointing results, emphasizing the importance of
      early diagnosis and effective primary therapy for IA. Despite this, a number of
      agents have been studied in the treatment of IA and have demonstrated efficacy in
      a salvage setting. These include lipid-based formulations of amphotericin B,
      caspofungin, itraconazole, voriconazole, posaconazole and micafungin.
      Combinations of echinocandins with either azoles or amphotericin B have also been
      studied in small series. Further studies are required, ideally comparing newer
      agents and treatment strategies in randomized clinical trials, to clarify the
      optimal approach to salvage treatment of IA in this challenging group of
      patients.

PMID- 18063605
TI  - Molecular identification of pathogenic fungi.
AB  - Systemic fungal infections represent a major cause of morbidity and mortality in
      immunocompromised patients. The ever-increasing number of yeast species
      associated with human infections that are not covered by conventional
      identification kits, and the fact that moulds isolated from deep infections are
      frequently impossible to identify using classical methods due to lack of
      sporulation, has driven the need for rapid, robust molecular identification
      techniques. We recently developed a rapid method of preparing fungal genomic DNAs
      using Whatman FTA filters, which has greatly facilitated molecular
      identification. Mould isolates cultured from dark grain mycetomas (destructive
      infections of skin/subcutaneous tissues that progress to involve muscle and bone)
      invariably fail to produce features by which they can be identified and were
      taxonomic mysteries. PCR amplification and sequencing of 250 bp of the internal
      transcribed spacer region 1 (ITS1) allowed us to distinguish between the known
      agents of mycetoma, to describe three new species associated with this disease
      and to define phylogenetic relationships. For yeasts, 153 isolates encompassing
      47 species that had failed to be identified using classical methods were
      unambiguously identified by conventional sequencing of 350 bp of the 26S rRNA
      D1D2 region. These represented 5% of the isolates examined and included common
      species with atypical biochemical and phenotypic profiles, and rarer species
      infrequently associated with infection. Our recent studies indicate that FTA
      extraction coupled with pyrosequencing of 25 bp of ITS2 could potentially
      identify most common yeast species from pure culture in half a day. Together,
      these data underscore the importance of molecular techniques for fungal
      identification.

PMID- 18063606
TI  - Thymoma accompanied by lichen planus.
AB  - Thymomas are associated at a high frequency with paraneoplastic autoimmune
      diseases. We treated a 64-year-old male with a thymoma, who also had lichen
      planus. The tumor was resected and diagnosed as thymoma, however, the symptoms
      associated with lichen planus did not subside and persisted. A preoperative
      examination showed an elevated serum level of squamous cell carcinoma antigen,
      which gradually decreased to normal after surgery. The findings of this case are
      interesting for understanding the correlation between a thymoma and autoimmune
      abnormalities.

PMID- 18063607
TI  - Entirely polytetrafluoroethylene coating for pacemaker system contact dermatitis.
AB  - A 63-year-old man underwent pacemaker implantation for complete atrio-ventricular
      block. The patient repeated admissions for skin necrosis, and generator or
      pacemaker system was re-implanted each time. The patient was admitted with skin
      necrosis of the generator pocket three years after re-implantation. A skin patch
      test was positive on almost all components of the pacemaker system. The patient
      underwent pacemaker system removal and re-implantation of polytetrafluoroethylene
      (PTFE) sheets coating pericardium leads and generator. There has been no
      recurrence. PTFE sheet coating is effective to treat pacemaker system contact
      dermatitis.

PMID- 18063608
TI  - Hysteroscopic myomectomy: a comprehensive review of surgical techniques.
AB  - Hysteroscopic myomectomy currently represents the standard minimally invasive
      surgical procedure for treating submucous fibroids, with abnormal uterine
      bleeding and reproductive issues being the most common indications. While
      hysteroscopic myomectomy has been shown to be safe and effective in the control
      of menstrual disorders, its effects on infertility remain unclear. The review
      provides a comprehensive survey of all hysteroscopic techniques used to treat
      fibroids found completely within the uterine cavity (G0) and those with
      intramural development (G1 and G2). MEDLINE and EMBASE searches identified
      published papers from 1970. The choice of the technique mostly depends on the
      intramural extension of the fibroid, as well as on personal experience and
      available equipment. 'Resectoscopic slicing' still represents the 'gold standard'
      technique for treating fibroids G0, even if several other effective techniques
      including ablation by neodymium-yttrium-aluminum-garnet laser, morcellation and
      office myomectomy have been proposed. On the other hand, the present review
      clearly indicates that there is still no single technique proven to be
      unequivocally superior for treating fibroids G1 and G2. Most techniques aim at
      the transformation of an intramural fibroid into a totally intracavitary lesion,
      thus avoiding a deep cut into the myometrium. At present, the 'cold loop'
      technique seems to represent the best option as it allows a safe and complete
      removal of such fibroids in just one surgical procedure, while respecting the
      surrounding healthy myometrium.

PMID- 18063609
TI  - Cytokine knockouts in reproduction: the use of gene ablation to dissect roles of
      cytokines in reproductive biology.
AB  - Cytokines play many diverse and important roles in reproductive biology, and
      dissecting the complex interactions between these proteins and the different
      reproductive organs is a difficult task. One approach is to use gene ablation, or
      'knockout', to analyse the effect of deletion of a single cytokine on mouse
      reproductive function. This review summarizes the essential roles of cytokines in
      reproductive biology that have been revealed by gene knockout studies, including
      development and regulation of the hypothalamo-pituitary-gondal axis, ovarian
      folliculogenesis, implantation and immune system modulation during pregnancy.
      However, successful utilization of this approach must consider the caveats
      associated with gene ablation studies, e.g. embryonic lethality, systemic effects
      of cytokine ablation on local reproductive processes and the limited exposure to
      pathogens in mice housed in laboratory conditions. New sophisticated technology
      that temporally or spatially regulates gene ablation can overcome some of these
      limitations. Discoveries on the roles of cytokines in reproductive function
      uncovered by gene ablation studies can now be applied to improve in vitro
      fertilization for infertile couples and in the development of contraceptive
      therapies.

PMID- 18063610
TI  - Non-drug industry funded research.

PMID- 18063611
TI  - Effect of European Clinical Trials Directive on academic drug trials in Denmark:
      retrospective study of applications to the Danish Medicines Agency 1993-2006.
AB  - OBJECTIVE: To determine the impact of the European Union's Clinical Trials
      Directive on the number of academic drug trials carried out in Denmark. DESIGN:
      Retrospective review of applications for drug trials to the Danish Medicines
      Agency, 1993-2006. REVIEW METHODS: Applications for drug trials for alternate
      years were classified as academic or commercial trials. A random subset of
      academic trials was reviewed for number of participants in and intended
      monitoring of the trials. RESULTS: Academic and commercial drug trials showed an
      identical steady decline from 1993 to 2006 and no noticeable change after 2004
      when good clinical practice became mandatory for academic trials. CONCLUSION: The
      Clinical Trials Directive introduced in May 2004 to ensure good clinical practice
      for academic drug trials was not associated with a decline in research activity
      in Denmark; presumably because good clinical practice units had already been in
      place in Danish universities since 1999. With such an infrastructure academic
      researchers can do drug trials under the same regulations as drug companies.

PMID- 18063613
TI  - Implementing practice based commissioning.

PMID- 18063612
TI  - Population screening for coeliac disease in primary care by district nurses using
      a rapid antibody test: diagnostic accuracy and feasibility study.
AB  - OBJECTIVE: To evaluate the feasibility and diagnostic accuracy of screening for
      coeliac disease by rapid detection of IgA antibodies to tissue transglutaminase
      performed in primary care. DESIGN: District nurses screened 6 year old children
      using rapid antibody testing of finger prick blood. They also collected capillary
      blood samples for laboratory determination of IgA and IgG antibodies to
      endomysium and IgA antibodies to tissue transglutaminase. Children with positive
      rapid test results were directly sent for biopsy of the small intestine. Setting
      Primary care in Jasz-Nagykun-Szolnok county, Hungary. PARTICIPANTS: 2690 children
      (77% of 6 year olds living in the county) and 120 nurses. MAIN OUTCOME MEASURES:
      Positivity for antibodies to endomysium or transglutaminase in the laboratory and
      coeliac disease confirmed at biopsy. RESULTS: 37 children (1.4%, 95% confidence
      interval 0.9% to 1.8%) had biopsy confirmed coeliac disease. Only five of these
      children had been diagnosed clinically before screening. Rapid testing had a
      78.1% sensitivity (70.0% to 89.3%) and 100% specificity (88.4% to 100%) for a
      final diagnosis of coeliac disease by biopsy. Sensitivity was 65.1% (50.2% to
      77.6%) and specificity was 100% (99.8% to 100%) compared with combined results of
      IgA and IgG laboratory tests. Trained laboratory workers detected 30 of the 31
      newly diagnosed IgA competent patients with the rapid test kit used blindly.
      Median time to biopsy after a positive rapid test result was significantly
      shorter (20 days, range 4-148) than after a positive laboratory result (142 days,
      70-256; P<0.001). Children with coeliac disease detected at screening were
      smaller and had worse health status than their peers but they improved on a
      gluten-free diet. CONCLUSIONS: A simple rapid antibody test enabled primary care
      nurses to detect patients with coeliac disease in the community who were not
      picked up in clinical care. Extra training is needed to improve sensitivity.

PMID- 18063614
TI  - Atrial fibrillation: Rate control and digoxin.

PMID- 18063615
TI  - Graduate medical school entry: Bad for state school applicants.

PMID- 18063616
TI  - Role of the doctor: Behold the factory worker.

PMID- 18063617
TI  - Role of the doctor: To care for patients' wellbeing.

PMID- 18063618
TI  - Quality and outcomes framework. Evidence of net benefit is lacking.

PMID- 18063619
TI  - Quality and outcomes framework. So what are we to do?

PMID- 18063620
TI  - Investigating renal impairment: Angioplasty's role is uncertain.

PMID- 18063622
TI  - GPs are struggling to gauge health needs of local people.

PMID- 18063625
TI  - UK government pledges 370m pounds sterling to improve cancer care.

PMID- 18063623
TI  - US gene therapy trial is to restart, despite patient's death.

PMID- 18063626
TI  - Mortality from measles fell by 91% in Africa from 2000 to 2006.

PMID- 18063628
TI  - GMC strikes Southall off medical register for serious professional misconduct.

PMID- 18063630
TI  - More mothers are dying from causes related to obesity.

PMID- 18063633
TI  - Dignitas is forced to offer its services from a former factory.

PMID- 18063634
TI  - Agency launches advice to reduce number of prescribing errors.

PMID- 18063635
TI  - People with learning disabilities are being let down by NHS.

PMID- 18063636
TI  - Smoking licences and cutting salt in food would reduce health inequalities.

PMID- 18063638
TI  - Holland plans chlamydia screening in 300,000 young people.

PMID- 18063640
TI  - Is infant male circumcision an abuse of the rights of the child? Yes.

PMID- 18063641
TI  - Is infant male circumcision an abuse of the rights of the child? No.

PMID- 18063642
TI  - Better safe than sorry?

PMID- 18063643
TI  - The road to hell...

PMID- 18063644
TI  - A perforated education.

PMID- 18063645
TI  - Medical aspects of male circumcision.

PMID- 18063650
TI  - Examining the minimal required elements of a computer-tailored intervention aimed
      at dietary fat reduction: results of a randomized controlled dismantling study.
AB  - This study investigated the minimally required feedback elements of a computer
      tailored dietary fat reduction intervention to be effective in improving fat
      intake. In all 588 Healthy Dutch adults were randomly allocated to one of four
      conditions in an randomized controlled trial: (i) feedback on dietary fat intake
      [personal feedback (P feedback)], (ii) P feedback and feedback on one's own
      behavior relative to that of peers [personal-normative feedback (PN feedback)],
      (iii) PN feedback and practical suggestions on how to change fat intake [personal
      normative-action feedback (PNA feedback)] and (iv) generic information. Data on
      fat intake, awareness of one's own fat intake and intention to change were
      collected 1 and 6 months post-intervention. Between-group differences were tested
      with analysis of variance. Among respondents with high fat intakes at baseline
      (risk consumers) and those who underestimated their fat intake at baseline
      (underestimators), differences in awareness and (saturated) fat intake were found
      between the generic and PNA feedback conditions. Compared with generic
      information P feedback was more effective in changing awareness and intention
      among the underestimators, and PN feedback was more effective in changing
      intention among both risk consumers and underestimators. In conclusion, the
      combination of personal, normative and action feedback is required for inducing
      change in fat intake and improving awareness of fat intake.

PMID- 18063651
TI  - The recent dramatic decline in road mortality in France: how drivers' attitudes
      towards road traffic safety changed between 2001 and 2004 in the GAZEL cohort.
AB  - A very significant decline in the number of road casualties has been observed
      recently in France, concomitantly with a dramatic increase in law enforcement.
      The aim of this study was (i) to assess changes in attitudes about road traffic
      accident (RTA) prevention initiatives in France from 2001 to 2004 and (ii) to
      identify factors associated with an increase in positive attitudes towards RTA
      prevention initiatives. In 2001 and 2004, 9216 participants reported their
      attitudes towards traffic safety using the same self-administered Driving
      Behaviour and Road Safety Questionnaire. Sociodemographic, psychological and
      behavioural data were also available. The mean change in scores analysis showed
      that support for relaxing existing regulations decreased significantly during
      this period, while support for heightened enforcement and stricter regulations
      showed some decrease but remained high overall, especially concerning blood
      alcohol content and speed controls. Multivariate analyses suggest that highly
      educated drivers changed their attitudes towards road safety regulations more
      than other categories. Our results suggest that increased traffic law enforcement
      measures led to increasing support for current restrictions. Even if support for
      additional traffic law enforcement began to wane slightly in 2004, a large part
      of our population remained in favour of strengthening law enforcement related to
      speeding and drunk driving.

PMID- 18063652
TI  - Motives for parenthood among couples attending a level 3 infertility clinic in
      the public health sector in South Africa.
AB  - BACKGROUND: Most African countries are pronatalistic with high total fertility
      rates and a low prevalence of voluntary childlessness. At present, limited data
      exist relating to the reasons why men and women desire children. This study
      explores parenthood motives among infertile couples from an urban community in
      South Africa. METHODS: The parenthood-motivation list, an instrument developed in
      the Netherlands for the assessment of parenthood motives and strength of desire
      for a child, was administrated to 50 couples (100 participants) who presented to
      an infertility clinic in a tertiary referral centre. The instrument discerns six
      parenthood motives comprising happiness, well-being, identity, parenthood,
      continuity and social control. RESULTS: The majority of participants endorsed
      most of the motives. The categories happiness and parenthood were the most
      frequent motives. Women endorsed more motives simultaneously when compared with
      men. The categories happiness, well-being and social control correlated
      positively with strength of desire for a child. Most men and women expressed a
      strong desire for a child. CONCLUSIONS: Men and women desired children for many
      reasons and with similar intensity. This diversity and intensity of parenthood
      motives appears to be a reflection of the value of children in our communities
      and further our understanding of the implications of involuntary childlessness.

PMID- 18063653
TI  - Bacterial contamination and over-dilution of commercial infant formula prepared
      by HIV-infected mothers in a Prevention of Mother-to-Child Transmission (PMTCT)
      Programme, South Africa.
AB  - To examine the safety of formula feeds used by mothers participating in a
      Prevention of Mother-to-Child Transmission (PMTCT) programme, contents of 94
      feeding bottles collected at a PMTCT-clinic were analysed. An additional 17
      samples were taken from already prepared feeds during home visits, as well as 21
      samples from bottles prepared under observation. Living conditions and
      educational levels were overall good and mothers had been counselled on safe
      formula preparation. Samples were analysed for faecal bacteria, using Escherichia
      coli and Enterococcus sp. as indicators. Protein concentration was used as an
      indicator of concentration of the formula. Out of 94, 63 (67%) of samples
      obtained at the clinic and 13/16 (81%) of available home samples were
      contaminated with faecal bacteria, compared to 8/21 (38%) of those prepared under
      observation. Out of 94, 58 (62%) of the clinic samples containing E. coli and
      23/94 (24%) of those containing Enterococcus sp. were contaminated with more than
      the US government recommended limit of 10 CFU/ml. Out of 94, 26 (28%) of samples
      obtained at the clinic, 8/17 (47%) of home samples and 3/21 (14%) of those
      prepared under observation were over-diluted, compared to standards. Many mothers
      did not follow recommended practices in preparing and feeding the bottles.

PMID- 18063654
TI  - An unusual cause of abnormal liver function in a patient with rheumatoid
      arthritis.

PMID- 18063655
TI  - Self-rated health and a healthy lifestyle are the most important predictors of
      survival in elderly women.
AB  - OBJECTIVE: to test the hypothesis that morbidity and health related behavioural
      factors are stronger than social factors as predictors of death among older
      women. METHODS: we used data from 12,422 participants in the Australian
      Longitudinal Study on Women's Health who were aged 70-75 in 1996. Proportional
      hazards models of survival up to 31 October 2005 were fitted separately for the
      whole cohort and those women who were initially in 'good health'. RESULTS: among
      the whole cohort, 18.7% died during the follow_up period. The strongest predictor
      of death was 'poor' or 'fair' self-rated health (with 52.3% and 28.0%,
      respectively, of women in these categories dying). Among the women in 'good
      health' at baseline 11.5% died, with current cigarette smoking (hazard ratio HR =
      2.19, 95% confidence interval (1.71, 2.81), physical inactivity (HR = 1.45 (1.17,
      1.81)), and age (HR = 1.10 (1.04, 1.16) per year) as statistically significant
      predictors of death. DISCUSSION: among older women, current health and health
      related behaviours are stronger predictors than social factors of relatively
      early mortality. Adopting a healthier lifestyle, by doing more exercise and not
      smoking, is beneficial even in old age.

PMID- 18063656
TI  - Modulation of 5-HT3 receptor desensitization by the light chain of microtubule
      associated protein 1B expressed in HEK 293 cells.
AB  - Regulation of ligand-gated ion channel (LGIC) function and trafficking by
      cytoskeleton proteins has been the topic of recent research. Here, we report that
      the light chain (LC1) of microtubule-associated protein 1B (MAP1B) specifically
      interacted with the 5-HT(3A) receptor, a predominant serotonin-gated ion channel
      in the brain. LC1 and 5-HT(3A) receptors were colocalized in central neurons and
      in HEK 293 cells expressing 5-HT(3A) receptors. LC1 reduced the steady-state
      density of 5-HT(3A) receptors at the membrane surface of HEK 293 cells and
      significantly accelerated receptor desensitization time constants from 3.8 +/-
      0.3 s to 0.8 +/- 0.1 s. However, LC1 did not significantly alter agonist binding
      affinity and single-channel conductance of 5-HT(3A) receptors. On the other hand,
      application of specific LC1 antisense oligonucleotides and nocodazole, a
      microtubule disruptor, significantly prolonged the desensitization time of the
      recombinant and native neuronal 5-HT(3) receptors by 3- to 6-fold. This kinetic
      change induced by nocodazole was completely rescued by addition of LC1 but not
      GABA(A) receptor-associated protein (GABARAP), suggesting that LC1 can
      specifically interact with 5-HT(3A) receptors. These observations suggest that
      the LC1-5-HT(3A) receptor interaction contributes to a mechanism that regulates
      receptor desensitization kinetics. Such dynamic regulation may play a role in
      reshaping the efficacy of 5-HT(3) receptor-mediated synaptic transmission.

PMID- 18063657
TI  - Caffeine - a valuable tool in excitation-contraction coupling research.

PMID- 18063658
TI  - The calcium channel alpha2/delta1 subunit is involved in extracellular
      signalling.
AB  - The alpha2/delta1 subunit forms part of the dihydropyridine receptor, an
      essential protein complex for excitation-contraction (EC) coupling in skeletal
      muscle. Because of the lack of a viable knock-out animal, little is known
      regarding the role of the alpha2/delta1 subunit in EC coupling or in other cell
      functions. Interestingly, the alpha2/delta1 appears before the alpha1 subunit in
      development and contains extracellular conserved domains known to be important in
      cell signalling and inter-protein interactions. These facts raise the possibility
      that the alpha2/delta1 subunit performs vital functions not associated with EC
      coupling. Here, we tested the hypothesis that the alpha2/delta1 subunit is
      important for interactions of muscle cells with their environment. Using confocal
      microscopy, we followed the immunolocalization of alpha2/delta1 and alpha1
      subunits with age. We found that in 2-day-old myotubes, the alpha2/delta1 subunit
      concentrated towards the ends of the cells, while the alpha1 subunit clustered
      near the centre. As myotubes aged (6-12 days), the alpha2/delta1 became evenly
      distributed along the myotubes and co-localized with alpha1. When the expression
      of alpha2/delta1 was blocked with siRNA, migration, attachment and spreading of
      myoblasts were impaired while the L-type calcium current remained unaffected. The
      results suggest a previously unidentified role of the alpha2/delta1 subunit in
      skeletal muscle and support the involvement of this protein in extracellular
      signalling. This new role of the alpha2/delta1 subunit may be crucial for muscle
      development, muscle repair and at times in which myoblast attachment and
      migration are fundamental.

PMID- 18063659
TI  - Ageing diminishes endothelium-dependent vasodilatation and tetrahydrobiopterin
      content in rat skeletal muscle arterioles.
AB  - Ageing reduces endothelium-dependent vasodilatation through an endothelial nitric
      oxide synthase (NOS) signalling pathway. The purpose of this study was to
      determine whether arginase activity diminishes endothelium-dependent
      vasodilatation in skeletal muscle arterioles from old rats, and whether NOS
      substrate (L-arginine) and cofactor (tetrahydrobiopterin; BH(4)) concentrations
      are reduced. First-order arterioles were isolated from the soleus muscle of young
      (6 months old) and old (24 months old) male Fischer 344 rats. In vitro changes in
      luminal diameter in response to stepwise increases in flow were determined in the
      presence of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (l-NAME, 10(-5)
      mol l(-1)), the arginase inhibitor N(omega)-hydroxy-nor-L-arginine (NOHA, 5 x 10(
      4) mol l(-1)), exogenous L-arginine (3 x 10(-3) mol l(-1)) or the precursor for
      BH(4) synthesis sepiapterin (1 micromol l(-1)). Arteriolar L-arginine and BH(4)
      content were determined via HPLC. Ageing decreased flow-mediated vasodilatation
      by 52%, and this difference was abolished with NOS inhibition. Neither inhibition
      of arginase activity nor addition of exogenous L-arginine had any effect on flow
      mediated vasodilatation; arteriolar l-arginine content was also not different
      between age groups. BH(4) content was lower in arterioles from old rats (94 +/- 8
      fmol (mg tissue)(-1)) relative to controls (234 +/- 21 fmol (mg tissue)(-1)), and
      sepiapterin elevated flow-mediated vasodilatation in arterioles from old rats.
      These results demonstrate that the impairment of endothelium-dependent
      vasodilatation induced by old age is due to an altered nitric oxide signalling
      mechanism in skeletal muscle arterioles, but is not the result of increased
      arginase activity and limited L-arginine substrate. Rather, the age-related
      deficit in flow-mediated vasodilatation appears to be the result, in part, of
      limited BH(4) bioavailability.

PMID- 18063660
TI  - KIR channels function as electrical amplifiers in rat vascular smooth muscle.
AB  - Strong inward rectifying K(+) (K(IR)) channels have been observed in vascular
      smooth muscle and can display negative slope conductance. In principle, this
      biophysical characteristic could enable K(IR) channels to 'amplify' responses
      initiated by other K(+) conductances. To test this, we have characterized the
      diversity of smooth muscle K(IR) properties in resistance arteries, confirmed the
      presence of negative slope conductance and then determined whether K(IR)
      inhibition alters the responsiveness of middle cerebral, coronary septal and
      third-order mesenteric arteries to K(+) channel activators. Our initial
      characterization revealed that smooth muscle K(IR) channels were highly expressed
      in cerebral and coronary, but not mesenteric arteries. These channels comprised
      K(IR)2.1 and 2.2 subunits and electrophysiological recordings demonstrated that
      they display negative slope conductance. Computational modelling predicted that a
      K(IR)-like current could amplify the hyperpolarization and dilatation initiated
      by a vascular K(+) conductance. This prediction was consistent with experimental
      observations which showed that 30 mum Ba(2+) attenuated the ability of K(+)
      channel activators to dilate cerebral and coronary arteries. This attenuation was
      absent in mesenteric arteries where smooth muscle K(IR) channels were poorly
      expressed. In summary, smooth muscle K(IR) expression varies among resistance
      arteries and when channel are expressed, their negative slope conductance
      amplifies responses initiated by smooth muscle and endothelial K(+) conductances.
      These findings highlight the fact that the subtle biophysical properties of K(IR)
      have a substantive, albeit indirect, role in enabling agonists to alter the
      electrical state of a multilayered artery.

PMID- 18063661
TI  - Developmental maturation of synaptic and extrasynaptic GABAA receptors in mouse
      thalamic ventrobasal neurones.
AB  - Thalamic ventrobasal (VB) relay neurones express multiple GABA(A) receptor
      subtypes mediating phasic and tonic inhibition. During postnatal development,
      marked changes in subunit expression occur, presumably reflecting changes in
      functional properties of neuronal networks. The aims of this study were to
      characterize the properties of synaptic and extrasynaptic GABA(A) receptors of
      developing VB neurones and investigate the role of the alpha(1) subunit during
      maturation of GABA-ergic transmission, using electrophysiology and
      immunohistochemistry in wild type (WT) and alpha(1)(0/0) mice and mice engineered
      to express diazepam-insensitive receptors (alpha(1H101R), alpha(2H101R)). In
      immature brain, rapid (P8/9-P10/11) developmental change to mIPSC kinetics and
      increased expression of extrasynaptic receptors (P8-27) formed by the alpha(4)
      and delta subunit occurred independently of the alpha(1) subunit. Subsequently (>
      or = P15), synaptic alpha(2) subunit/gephyrin clusters of WT VB neurones were
      replaced by those containing the alpha(1) subunit. Surprisingly, in alpha(1)(0/0)
      VB neurones the frequency of mIPSCs decreased between P12 and P27, because the
      alpha(2) subunit also disappeared from these cells. The loss of synaptic GABA(A)
      receptors led to a delayed disruption of gephyrin clusters. Despite these
      alterations, GABA-ergic terminals were preserved, perhaps maintaining tonic
      inhibition. These results demonstrate that maturation of synaptic and
      extrasynaptic GABA(A) receptors in VB follows a developmental programme
      independent of the alpha(1) subunit. Changes to synaptic GABA(A) receptor
      function and the increased expression of extrasynaptic GABA(A) receptors
      represent two distinct mechanisms for fine-tuning GABA-ergic control of thalamic
      relay neurone activity during development.

PMID- 18063662
TI  - The kinetics of competitive antagonism of nicotinic acetylcholine receptors at
      physiological temperature.
AB  - Detailed information about the ligand-binding site of nicotinic acetylcholine
      receptors has emerged from structural and mutagenesis experiments. However, these
      approaches provide only static images of ligand-receptor interactions. Kinetic
      measurements of changes in protein function are needed to develop a more dynamic
      picture. Previously, we measured association and dissociation rate constants for
      competitive inhibition of current through embryonic muscle acetylcholine receptor
      channels at 25 degrees C. Little is known about competitive antagonism at
      physiological temperatures. Here, we performed measurements at 37 degrees C and
      used thermodynamics to estimate the energetics of antagonism. We used rapid
      solution exchange protocols to determine equilibrium and kinetics of inhibition
      of acetylcholine-activated currents in outside-out patches by (+)-tubocurarine,
      pancuronium and cisatracurium. Kinetic rates as high as 600 s(-1) were resolved
      by this technique. Binding was primarily enthalpy driven. The 12 degrees C
      increase in temperature decreased equilibrium antagonist binding by 1.7- to 1.9
      fold. In contrast, association and dissociation rate constants increased 1.9- to
      6.0-fold. Activation energies for dissociation were 90 +/- 6, 106 +/- 8 and 116
      +/- 10 kJ mol(-1) for cisatracurium, (+)-tubocurarine and pancuronium,
      respectively. The corresponding apparent activation energies for association were
      38 +/- 6, 85 +/- 6 and 107 +/- 13 kJ mol(-1). The higher activation energy for
      association of (+)-tubocurarine and pancuronium compared with cisatracurium is
      notable. This may arise from either a more superficial binding site for the large
      antagonist cisatracurium compared to the other ligands, or from a change in
      receptor conformation upon binding of (+)-tubocurarine and pancuronium but not
      cisatracurium. Differences in ligand desolvation and ligand conformation are not
      likely to be important.

PMID- 18063663
TI  - Muscle [phosphocreatine] dynamics following the onset of exercise in humans: the
      influence of baseline work-rate.
AB  - The kinetics of pulmonary O(2) uptake is known to be substantially slower when
      exercise is initiated from a baseline of lower-intensity exercise rather than
      from rest. However, it is not known whether putative intracellular regulators of
      mitochondrial respiration (and in particular the phosphocreatine concentration,
      [PCr]) show similar non-linearities in their response dynamics. The purpose of
      this study was therefore to investigate the influence of baseline metabolic rate
      on muscle [PCr] kinetics (as assessed using (31)P-magnetic resonance
      spectroscopy) following the onset of exercise. Seven male subjects completed
      'step' tests to heavy-intensity exercise (80% of peak work-rate) from a resting
      baseline and also from a baseline of moderate-intensity exercise (40% of peak
      work-rate) using a single-leg knee-extensor ergometer situated inside the bore of
      a 1.5 T super-conducting magnet. The time constant describing the kinetics of the
      initial exponential-like fall in [PCr] was significantly different between rest
      to-moderate (25 +/- 14 s), rest-to-heavy (48 +/- 11 s) and moderate-to-heavy
      exercise (95 +/- 40 s) (P < 0.05 for all comparisons). A delayed-onset 'slow
      component' in the [PCr] response was observed in all subjects during rest-to
      heavy exercise, but was attenuated in the moderate-to-heavy exercise condition.
      These data indicate that muscle [PCr] kinetics does not conform to 'linear, first
      order' behaviour during dynamic exercise, and thus have implications for
      understanding the regulation of muscle oxidative metabolism.

PMID- 18063664
TI  - Accumulation of cytoplasmic calcium, but not apamin-sensitive
      afterhyperpolarization current, during high frequency firing in rat subthalamic
      nucleus cells.
AB  - The autonomous firing pattern of neurons in the rat subthalamic nucleus (STN) is
      shaped by action potential afterhyperpolarization currents. One of these is an
      apamin-sensitive calcium-dependent potassium current (SK). The duration of SK
      current is usually considered to be limited by the clearance of calcium from the
      vicinity of the channel. When the cell is driven to fire faster, calcium is
      expected to accumulate, and this is expected to result in accumulation of calcium
      dependent AHP current. We measured the time course of calcium transients in the
      soma and proximal dendrites of STN neurons during spontaneous firing and their
      accumulation during driven firing. We compared these to the time course and
      accumulation of AHP currents using whole-cell and perforated patch recordings.
      During spontaneous firing, a rise in free cytoplasmic calcium was seen after each
      action potential, and decayed with a time constant of about 200 ms in the soma,
      and 80 ms in the dendrites. At rates higher than 10 Hz, calcium transients
      accumulated as predicted. In addition, there was a slow calcium transient not
      predicted by summation of action potentials that became more pronounced at high
      firing frequency. Spike AHP currents were measured in voltage clamp as tail
      currents after 2 ms voltage pulses that triggered action currents. Apamin
      sensitive AHP (SK) current was measured by subtraction of tail currents obtained
      before and after treatment with apamin. SK current peaked between 10 and 15 ms
      after an action potential, had a decay time constant of about 30 ms, and showed
      no accumulation. At frequencies between 5 and 200 spikes s(-1), the maximal SK
      current remained the same as that evoked by a single action potential. AHP
      current did not have time to decay between action potentials, so at frequencies
      above 50 spikes s(-1) the apamin-sensitive current was effectively constant.
      These results are inconsistent with the view that the decay of SK current is
      governed by calcium dynamics. They suggest that the calcium is present at the SK
      channel for a very short time after each action potential, and the current decays
      at a rate set by the deactivation kinetics of the SK channel. At high rates,
      repetitive firing was governed by a fast apamin-insensitive AHP current that did
      not accumulate, but rather showed depression with increases in activation
      frequency. A slowly accumulating AHP current, also insensitive to apamin, was
      extremely small at low rates but became significant with higher firing rates.

PMID- 18063665
TI  - The group IV afferent neuron expresses multiple receptor alterations in
      cardiomyopathyic rats: evidence at the cannabinoid CB1 receptor.
AB  - The exercise pressor reflex (EPR) is an important neural mechanism that controls
      blood pressure and heart rate during static muscle contraction. It has been
      previously demonstrated that the EPR is exaggerated in cardiomyopathy. Both
      mechanically (group III) and metabolically (group IV) sensitive afferent neurons
      are important to this reflex in normal humans and animals. In cardiomyopathy,
      however, the metabolically sensitive afferents are less responsive to activation
      whereas the mechanically sensitive fibres are overactive. We have demonstrated
      that this overactivity is responsible for the exaggeration in the EPR. Of
      importance, we have also demonstrated that the reduced responsiveness in the
      group IV afferent neuron is an initiating factor in the development of the
      exaggerated EPR. To date, the mechanism mediating this reduced group IV
      responsiveness remains unclear. Given that group IV afferent neurons are
      activated via chemically sensitive receptors, it is logical to suggest that
      changes in receptor function are responsible for the blunted behaviour of group
      IV neurons in cardiomyopathy. In order to test this postulate, however, potential
      receptor candidates must first be identified. The transient receptor potential
      vanilloid 1 (TRPv1) receptor is a non-selective cation channel that serves as a
      marker of the group IV afferent neurons in the periphery. We have demonstrated
      that the TRPv1 is abnormal in cardiomyopathy. It has been shown that the TRPv1
      receptor is colocalized with the cannabinoid 1 (CB(1)) receptor on group IV
      afferent neurons. Therefore, we hypothesized that the function of CB(1) receptors
      is abnormal in cardiomyopathy. We explored this possibility by using anandamide
      (AEA), an endogenously produced cannabinoid that has been shown to control blood
      pressure via activation of the CB(1) receptor. In these studies, we evaluated the
      cardiovascular responses to intra-arterial injection of AEA into the hindlimb of
      normal, cardiomyopathic and neonatally capsaicin-treated (NNCAP) rats (rats that
      lack group IV afferent neurons) to determine whether administration of AEA
      results in abnormal responses of group IV afferent neurons in cardiomyopathic
      rats. We determined that AEA controls changes in blood pressure, predominately
      via activation of the CB(1) receptor in this preparation. We further observed
      that the blood pressure response to AEA is blunted in cardiomyopathic rats when
      compared to normal rats. We also observed a reduced blood pressure response to
      AEA in NNCAP animals, indicating that AEA is acting on group IV afferent neurons
      in this preparation. To determine whether programmed cell death could account for
      the decreased responsiveness that we observed during activation of the CB(1) and
      TRPv1 receptors on group IV afferent neurons in heart failure, we performed
      terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL)
      assay. We observed no evidence of cell death within the dorsal root ganglia in
      rats with cardiomyopathy. The data suggest that the responsiveness of CB(1)
      receptors on group IV afferent neurons is blunted in cardiomyopathy. Importantly,
      these data indicate that group IV primary afferent neurons express multiple
      receptor defects in cardiomyopathy that may contribute to the decreased CB(1)
      receptor sensitivity in this disease.

PMID- 18063666
TI  - Determining Ca2+-sensor binding time and its variability in evoked
      neurotransmitter release.
AB  - The speed and reliability of neuronal reactions are important factors for proper
      functioning of the nervous system. To understand how organisms use protein
      molecules to carry out very fast biological actions, we quantified single
      molecule reaction time and its variability in synaptic transmission. From the
      synaptic delay of crayfish neuromuscular synapses the time for a few Ca(2+) ions
      to bind with their sensors in evoked neurotransmitter release was estimated. In
      standard crayfish saline at room temperature, the average Ca(2+) binding time was
      0.12 ms for the first evoked quanta. At elevated extracellular Ca(2+)
      concentrations this binding time reached a limit due to saturation of Ca(2+)
      influx. Analysis of the synaptic delay variance at various Ca(2+) concentrations
      revealed that the variability of the Ca(2+)-sensor binding time is the major
      source of the temporal variability of synaptic transmission, and that the Ca(2+)
      independent molecular reactions after Ca(2+) influx were less stochastic. The
      results provide insights into how organisms maximize reaction speed and
      reliability.

PMID- 18063667
TI  - Comprehensive evaluation of the genetic variants of interferon regulatory factor
      5 (IRF5) reveals a novel 5 bp length polymorphism as strong risk factor for
      systemic lupus erythematosus.
AB  - We analyzed a comprehensive set of single-nucleotide polymorphisms (SNPs) and
      length polymorphisms in the interferon regulatory factor 5 (IRF5) gene for their
      association with the autoimmune disease systemic lupus erythematosus (SLE) in 485
      Swedish patients and 563 controls. We found 16 SNPs and two length polymorphisms
      that display association with SLE (P < 0.0005, OR > 1.4). Using a Bayesian model
      selection and averaging approach we identified parsimonious models with exactly
      two variants of IRF5 that are independently associated with SLE. The variants of
      IRF5 with the highest posterior probabilities (1.00 and 0.71, respectively) of
      being causal in SLE are a SNP (rs10488631) located 3' of IRF5, and a novel CGGGG
      insertion-deletion (indel) polymorphism located 64 bp upstream of the first
      untranslated exon (exon 1A) of IRF5. The CGGGG indel explains the association
      signal from multiple SNPs in the IRF5 gene, including rs2004640, rs10954213 and
      rs729302 previously considered to be causal variants in SLE. The CGGGG indel
      contains three or four repeats of the sequence CGGGG with the longer allele
      containing an additional SP1 binding site as the risk allele for SLE. Using
      electrophoretic mobility shift assays we show increased binding of protein to the
      risk allele of the CGGGG indel and using a minigene reporter assay we show
      increased expression of IRF5 mRNA from a promoter containing this allele.
      Increased expression of IRF5 protein was observed in peripheral blood mononuclear
      cells from SLE patients carrying the risk allele of the CGGGG indel. We have
      found that the same IRF5 allele also confers risk for inflammatory bowel diseases
      and multiple sclerosis, suggesting a general role for IRF5 in autoimmune
      diseases.

PMID- 18063668
TI  - The dyslexia-associated gene KIAA0319 encodes highly N- and O-glycosylated plasma
      membrane and secreted isoforms.
AB  - The KIAA0319 gene has been recently associated with developmental dyslexia and
      shown to be involved in neuronal migration. The deduced KIAA0319 protein contains
      several polycystic kidney disease (PKD) domains which may mediate the interaction
      between neurons and glial fibres during neuronal migration. We have previously
      reported the presence of several alternative splicing variants, some of which are
      predicted to affect the deduced protein. In this study, we over-expressed
      constructs containing the main form (A) and two alternative variants (B and C) of
      KIAA0319. We show that the full-length KIAA0319 (A) is a type I plasma membrane
      protein, a topology consistent with its proposed function in neuronal migration.
      The oligomeric status of KIAA0319 is mainly dimeric, and this condition depends
      on the cysteine-rich regions of the protein, especially the transmembrane (TM)
      domain and surrounding sequence. KIAA0319 is highly glycosylated in different
      mammalian cell lines. The central region including the PKD domains is N
      glycosylated. Furthermore, a short fragment N-terminal to the PKD domains
      contains mucin-type O-glycosylation. The two alternative isoforms are soluble
      proteins lacking the TM domain and, interestingly, only isoform B is secreted.
      KIAA0319-deletion proteins lacking the TM domain were also secreted. These
      results suggest that KIAA0319 could be involved not only in cell-cell
      interactions, but also in signalling.

PMID- 18063669
TI  - Evidence that common variation in NEDD9 is associated with susceptibility to late
      onset Alzheimer's and Parkinson's disease.
AB  - Late-onset Alzheimer's disease (LOAD) and Parkinson's disease (PD) are the most
      common neurodegenerative disorders and in both diseases susceptibility is known
      to be influenced by genes. We set out to identify novel susceptibility genes for
      LOAD by performing a large scale, multi-tiered association study testing 4692
      single nucleotide polymorphism (SNPs). We identified a SNP within a putative
      transcription factor binding site in the NEDD9 gene (neural precursor cell
      expressed, developmentally down-regulated), that shows good evidence of
      association with disease risk in four out of five LOAD samples [N = 3521, P =
      5.38x10(-6), odds ratio (OR) = 1.38 (1.20-1.59)] and in addition, we observed a
      similar pattern of association in two PD sample sets [N = 1464, P = 0.0145, OR
      =1.31 (1.05-1.62)]. In exploring a potential mechanism for the association, we
      observed that expression of NEDD9 and APOE show a strong inverse correlation in
      the hippocampus of Alzheimer's cases. These data implicate NEDD9 as a novel
      susceptibility gene for LOAD and possibly PD.

PMID- 18063670
TI  - Th1 but not Th17 cells predominate in the joints of patients with rheumatoid
      arthritis.
AB  - OBJECTIVES: Recent animal studies have revealed critical roles of interleukin
      (IL)17, which is produced by a newly identified subset of helper T cells, Th17
      cells, in the development of autoimmune diseases including arthritis. However, in
      human rheumatoid arthritis (RA), detailed characteristics and the prevalence of
      Th17 cells are unclear. METHODS: Peripheral blood mononuclear cells (PBMC) were
      obtained from 123 patients with RA and 28 healthy controls. Mononuclear cells
      were also prepared from synovial membrane or synovial fluid of 12 patients with
      RA. IL17 (IL17A) positive T cells were identified by a flow cytometer after ex
      vivo stimulation with phorbol myristate acetate and ionomycin. Disease activity
      was assessed with the 28-joint Disease Activity Score (DAS28). RESULTS: IL17
      positive cells were detected in CD45RO+ CD4 T cells. Most IL17 positive T cells
      produced neither interferon (IFN)gamma nor IL4, but tumour necrosis factor
      (TNF)alpha similar to murine Th17 cells. The frequency of Th17 cells was neither
      increased in RA nor correlated with DAS28. Unexpectedly, the frequency of Th17
      cells was significantly decreased in the joints compared with PBMC of the same
      patients with RA, whereas Th1 cells were more abundant in the joints than in
      PBMC. CONCLUSIONS: We could not obtain evidence that positively supports
      predominance of Th17 cells in RA. Further careful investigation is necessary
      before clinical application of IL17-targeting therapy.

PMID- 18063671
TI  - Treatment with a CO-releasing molecule (CORM-3) reduces joint inflammation and
      erosion in murine collagen-induced arthritis.
AB  - OBJECTIVE: CO-releasing molecules (CO-RMs) are a novel class of anti-inflammatory
      agents. We have examined the possible therapeutic effects of CORM-3 in collagen
      induced arthritis (CIA). METHODS: Arthritis was induced in DBA-1/J mice by type
      II collagen. Animals were treated with CORM-3 (5 and 10 mg/kg/day,
      intraperitoneally) or the inactive compound iCORM-3 (10 mg/kg/day,
      intraperitoneally) unable to release CO, from days 22 to 31. Production of anti
      type II collagen antibodies, cytokines and cartilage olimeric matrix protein
      (COMP) was evaluated by enzyme-linked immunosorbent assay, and prostaglandin E(2)
      (PGE(2)) by radioimmunoassay. Localisation of cyclooxygenase-2 (COX-2), haem
      oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1) and receptor
      activator of nuclear factor kappaB ligand (RANKL) was examined by
      immunohistochemistry. RESULTS: Therapeutic administration of CORM-3 suppressed
      clinical and histopathological manifestations of disease. The levels of PGE(2),
      interleukin (IL)1beta, IL2, IL6, IL10 and tumour necrosis factor (TNF)alpha in
      joint tissues were inhibited by CORM-3. By contrast, CORM-3 augmented IL4. Anti
      type II collagen antibodies and COMP levels in serum were reduced by CORM-3.
      Treatment with CORM-3 decreased cellular infiltration, joint inflammation and
      destruction, as well as the expression of COX-2, ICAM-1 and RANKL, whereas HO-1
      increased. These beneficial effects were due to CO release, as iCORM-3 was
      ineffective. CONCLUSION: This study reveals the antiarthritic properties of CORM
      3 in the CIA model and supports the notion that CO-RMs could be developed as a
      novel strategy for the treatment of inflammatory and arthritic conditions.

PMID- 18063672
TI  - Prevalence and clinical associations of anti-Ku antibodies in patients with
      systemic sclerosis: a European EUSTAR-initiated multi-centre case-control study.
AB  - OBJECTIVES: To determine the prevalence of anti-Ku antibodies in 625 patients
      with systemic sclerosis (SSc) from six European rheumatological centres and to
      evaluate their clinical and serological characteristics. METHODS: Sera of 625
      consecutive patients with either limited cutaneous or diffuse cutaneous SSc were
      tested for antibodies to Ku antigen together with other extractable nuclear
      antigens by counterimmunoelectrophoresis. A case-control design with calculation
      of bootstrap 95% confidence intervals derived from anti-Ku negative control
      patients was used to evaluate clinical associations of anti-Ku antibodies. Sera
      from anti-Ku positive patients with SSc and a control group were additionally
      tested by immunofluorescence on Hep-2 cell substrates and line immunoassay.
      RESULTS: Anti-Ku antibodies were found in the sera of 14/625 (2.2%) patients with
      SSc. Of 14 anti-Ku positive patients with SSc, 10 had no other anti-extractable
      nuclear antigen (ENA) antibodies detected by counterimmunoelectrophoresis. Using
      a case-control study design, anti-Ku antibodies were significantly associated
      with musculoskeletal manifestations such as clinical markers of myositis,
      arthritis and joint contractures. In addition, a significant negative correlation
      of anti-Ku antibodies was found with vascular manifestation such as fingertip
      ulcers and teleangiectasias. There was a striking absence of anti-centromere
      antibodies as well as anti- polymyositis (PM)/scleroderma (Scl) antibodies in
      patients that were anti-Ku positive. As expected, anti-Scl70 and punctate
      nucleolar immunofluorescence patterns were present only in single cases.
      CONCLUSION: This is the largest cohort to date focusing on the prevalence of anti
      Ku antibodies in patients with SSc. The case-control approach was able to
      demonstrate a clinically distinct subset of anti-Ku positive patients with SSc
      with only relative clinical differences in skeletal features. However, the
      notable exceptions were signs of myositis. This shows the importance of anti-Ku
      antibody detection for the prediction of this specific clinical subset.

PMID- 18063673
TI  - Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms
      associations with ankylosing spondylitis.
AB  - OBJECTIVES: The aim of the current study was to determine the contribution of
      interleukin (IL)1 gene cluster polymorphisms previously implicated in
      susceptibility for ankylosing spondylitis (AS) to AS susceptibility in different
      populations worldwide. METHODS: Nine polymorphisms in the IL1 gene cluster
      members IL1A (rs2856836, rs17561 and rs1894399), IL1B (rs16944), IL1F10
      (rs3811058) and IL1RN (rs419598, the IL1RA VNTR, rs315952 and rs315951) were
      genotyped in 2675 AS cases and 2592 healthy controls recruited in 12 different
      centres in 10 countries. Association of variants with AS was tested by Mantel
      Haenszel random effects analysis. RESULTS: Strong association was observed with
      three single nucleotide polymorphisms (SNPs) in the IL1A gene (rs2856836,
      rs17561, rs1894399, p = 0.0036, 0.000019 and 0.0003, respectively). There was no
      evidence of significant heterogeneity of effects between centres, and no evidence
      of non-combinability of findings. The population attributable risk fraction of
      these variants in Caucasians is estimated at 4-6%. CONCLUSIONS: This study
      confirms that IL1A is associated with susceptibility to AS. Association of the
      other IL1 gene complex members could not be excluded in specific populations.
      Prospective meta-analysis is a useful tool in confirmation studies of genes
      associated with complex genetic disorders such as AS, providing sufficiently
      large sample sizes to produce robust findings often not achieved in smaller
      individual cohorts.

PMID- 18063674
TI  - Association of a gene expression profile from whole blood with disease activity
      in systemic lupus erythaematosus.
AB  - OBJECTIVE: To determine whether peripheral blood gene expression of patients with
      systemic lupus erythaematosus (SLE) correlates with disease activity measured
      using the SLE Disease Activity Index 2000 (SLEDAI-2K). METHODS: RNA was isolated
      from peripheral blood of 269 patients with SLE and profiled on a custom
      microarray. Hierarchical clustering and a heat map were used to categorise
      samples into major clusters based on gene expression pattern. Correlates,
      including demographic and disease-related characteristics such as SLEDAI-2K
      score, of the major sample clusters were compared using multivariate regression
      models. RESULTS: A set of 31 interferon (IFN)-regulated genes were seen to be
      driving the separations of samples into two clusters, one characterised by a
      relatively high IFN-regulated gene signature (n = 150) and the other by a
      relatively low IFN-regulated gene signature (n = 119). Disease activity measured
      using the SLEDAI-2K was significantly correlated with the high IFN gene
      signature. In multivariate regression analysis the immunological component of the
      SLEDAI-2K was a significant correlate of the high IFN gene signature as was
      presence of antibodies to U1RNP. There were no discernable correlates of the 156
      non-IFN regulated genes profiled on the custom array. CONCLUSION: Peripheral
      blood gene expression profiling (GEP) in SLE allows patients to be categorised
      into two groups based on a high or low IFN gene signature. Disease activity
      measured using the SLEDAI-2K is correlated with the high IFN gene signature,
      indicating that GEP may be a useful biomarker of disease activity in SLE.

PMID- 18063675
TI  - Follicle-stimulating hormone-induced Galphah/phospholipase C-delta1 signaling
      mediating a noncapacitative Ca2+ influx through T-type Ca2+ channels in rat
      sertoli cells.
AB  - Our previous study demonstrated that FSH-induced immediate Ca(2+) influx in rat
      Sertoli cells (SCs) is mediated by the Galphah/phospholipase C-delta1 (PLC
      delta1) signaling pathway. As to which Ca(2+) channel is responsible for such
      Ca(2+) influx was not understood. In this study, thapsigargin triggered an in
      store calcium release and evoked a 1.5-fold elevation of intracellular Ca(2+) in
      Ca(2+)-free media, whereas FSH exhibited no effect. The readdition of CaCl(2)
      (2.5 mm) to FSH-pretreated or thapsigargin-sensitized SCs in Ca(2+)-free media
      immediately elicited a rapid Ca(2+) influx or a 2-fold increase of second
      intracellular Ca(2+) elevation, respectively. The addition of Ca(2+) chelator
      EGTA (0.2 mm) reduced the FSH-induced elevation of intracellular Ca(2+) in SCs
      incubated with CaCl(2). However, pretreatment with dantrolene (25 microM), which
      inhibits in-store calcium release, did not affect the FSH-induced elevation of
      intracellular Ca(2+). NiCl(2) (10 microM), a T-type calcium channel blocker,
      abolished the FSH-induced SC Ca(2+) influx. Furthermore, mibefradil (10 and 100
      microm), another specific blocker for T-type Ca(2+) channels, dose-dependently
      suppressed the FSH-induced Ca(2+) influx. In contrast, nifedipine (10 and 50
      microm) or omega-conotoxin GVIA (100 and 500 nm), blocker of L- or N-type Ca(2+)
      channels, respectively, did not affect the FSH-induced SC Ca(2+) influx. On the
      other hand, FSH-induced Ca(2+) influx was significantly reduced by pretreatment
      of SCs with myristoylated synthetic peptide (0.1 and 1 microm) of PLC-delta1
      fragment TIPWNSLKQGYRHVHLL but not affected by 2',5'-dideoxyadenosine (3 and 15
      microm), a selective inhibitor of adenylate cyclase. In conclusion, the FSH
      induced Galphah/PLC-delta1 pathway-dependent Ca(2+) influx of rat SCs is mediated
      by T-type Ca(2+) channels and independent of in-store calcium release.

PMID- 18063676
TI  - TrkB agonists ameliorate obesity and associated metabolic conditions in mice.
AB  - Mutations in the tyrosine kinase receptor trkB or in one of its natural ligands,
      brain-derived neurotrophic factor (BDNF), lead to severe hyperphagia and obesity
      in rodents and/or humans. Here, we show that peripheral administration of
      neurotrophin-4 (NT4), the second natural ligand for trkB, suppresses appetite and
      body weight in a dose-dependent manner in several murine models of obesity. NT4
      treatment increased lipolysis, reduced body fat content and leptin, and elicited
      long-lasting amelioration of hypertriglyceridemia and hyperglycemia. After
      treatment termination, body weight gradually recovered to control levels in obese
      mice with functional leptin receptor. A single intrahypothalamic application of
      minute amounts of NT4 or an agonist trkB antibody also reduced food intake and
      body weight in mice. Taken together with the genetic evidence, our findings
      support the concept that trkB signaling, which originates in the hypothalamus,
      directly modulates appetite, metabolism, and taste preference downstream of the
      leptin and melanocortin 4 receptor. The trkB agonists mediate anorexic and weight
      reducing effects independent of stress induction, visceral discomfort, or pain
      sensitization and thus emerge as a potential therapeutic for metabolic disorders.

PMID- 18063677
TI  - Side population does not define stem cell-like cancer cells in the adrenocortical
      carcinoma cell line NCI h295R.
AB  - Recent evidence suggests the existence of a stem cell-like subpopulation of cells
      in hematological and solid tumor entities, which determine the malignant
      phenotype of a given tumor through their proliferative potential and chemotherapy
      resistance. A recently used technique for the isolation of this cell population
      is through exclusion of the vital dye Hoechst 33342, which defines the so-called
      side population (SP). Herein we demonstrate the presence of SP cells in a variety
      of adrenal specimens, including primary cultures of human adrenocortical tumors
      and normal adrenal glands as well as established human and murine adrenocortical
      cancer cell lines by fluorescence-activated cell sorter analysis and confocal
      microscopy. On a functional level, SP cells from the human adrenocortical tumor
      cell line NCI h295R revealed an expression pattern consistent with a less
      differentiated phenotype, including lower expression of steroidogenic enzymes
      such as steroid acute regulatory protein (StAR) and side-chain cleavage enzyme
      (P450scc) in comparison with non-SP cells. However, proliferation between SP and
      non-SP cells did not differ (105.6 +/- 18.1 vs. 100.0 +/- 3.5%). Furthermore, re
      sorting and tracing experiments revealed the capacity for both cell types to give
      rise to the original SP- and non-SP-containing cell population. Similarly to the
      baseline growth kinetics, no survival benefit was evident in SP cells after
      treatment with cytotoxic agents commonly used in adrenocortical carcinomas. Taken
      together, these findings provide evidence that Hoechst dye exclusion, in contrast
      to what has been reported for other tumor entities, is not a major tumor stem
      cell defining marker in adrenocortical NCI h295R tumor cells.

PMID- 18063678
TI  - Uteroplacental insufficiency after bilateral uterine artery ligation in the rat:
      impact on postnatal glucose and lipid metabolism and evidence for metabolic
      programming of the offspring by sham operation.
AB  - Ligation of the uterine arteries (LIG) in rats serves as a model of intrauterine
      growth restriction and subsequent developmental programming of impaired glucose
      tolerance, hyperinsulinemia, and adiposity in the offspring. Its impact on lipid
      metabolism has been less well investigated. We compared parameters of glucose and
      lipid metabolism and glucocorticoid levels in the offspring of dams that
      underwent either LIG or sham operation (SOP) with those of untreated controls.
      Blood parameters including insulin, leptin, and visfatin as well as body weight,
      food intake, and creatinine clearance were recorded up to an age of 30 wk.
      Glucose tolerance tests were performed, and both leptin and visfatin expression
      in liver, muscle, and epididymal and mesenteric fat was quantified by RT-PCR.
      After catch-up growth, weight gain of all groups was similar, despite lower food
      intake of the LIG rats. LIG offspring showed impaired glucose tolerance from the
      age of 15 wk as well as elevated glycosylated hemoglobin and corticosterone
      levels. However, the body fat content of both LIG and SOP animals increased
      relative to controls, and both showed elevated triglyceride, total cholesterol,
      and leptin levels as well as a reduced proportion of high-density lipoprotein
      cholesterol. Thus, use of the LIG model requires both SOP and untreated controls.
      Although only LIG is associated with impaired glucose tolerance, pathogenic
      programming of the lipid metabolism can also be induced by SOP. Visfatin does not
      appear to be involved in the disturbed glucose metabolism after intrauterine
      growth restriction and may represent only a marker of fat accumulation.

PMID- 18063679
TI  - Effects of kisspeptin-10 on the electrophysiological manifestation of
      gonadotropin-releasing hormone pulse generator activity in the female rat.
AB  - Kisspeptins are extraordinarily potent in stimulating gonadotropic hormone
      secretion via an action on the hypothalamic GnRH neural system. Because the
      physiological frequency of the GnRH pulse generator is a critical component of
      the control system that governs reproductive processes, the aim of this study was
      to examine the effect of kisspeptin-10 on pulsatile LH secretion and on the
      electrophysiological manifestation of GnRH pulse generator activity to determine
      frequency modulatory effects. Adult Sprague Dawley rats were ovariectomized and
      chronically implanted with electrodes in the arcuate nucleus to record the
      characteristic increases in hypothalamic multiunit electrical activity volleys
      coincident with the initiation of each LH pulse measured in peripheral blood
      and/or indwelling cardiac catheters for the collection of blood samples (25
      microl) every 5 min for 6-7 h for the measurement of LH. Intravenous infusion of
      kisspeptin-10 (7.5, 35, and 100 nmol) induced a dose-dependent increase in LH
      secretion. The stimulatory effect of kisspeptin-10 (100 nmol) on LH secretion was
      blocked by the GnRH antagonist cetrorelix, precluding a singular action on
      gonadotropes. Unexpectedly, however, the marked increase in LH release in
      response to kisspeptin-10 (100 nmol) administration was not accompanied by any
      change in multiunit electrical activity volley frequency. It seem unlikely,
      therefore, that kisspeptin-10 has an appreciable frequency modulatory effect on
      GnRH pulse generator activity in the female rat.

PMID- 18063680
TI  - Melatonin stimulates the release of growth hormone and prolactin by a possible
      induction of the expression of frog growth hormone-releasing peptide and its
      related peptide-2 in the amphibian hypothalamus.
AB  - We recently identified a novel hypothalamic neuropeptide stimulating GH release
      in bullfrogs and termed it frog GH-releasing peptide (fGRP). The fGRP precursor
      encodes fGRP and its related peptides (fGRP-RP-1, -RP-2, and -RP-3), and fGRP-RP
      2 also stimulates GH and prolactin (PRL) release. Cell bodies and terminals
      containing these neuropeptides are localized in the suprachiasmatic nucleus (SCN)
      and median eminence, respectively. To understand the physiological role of fGRP
      and fGRP-RP-2, we investigated the mechanisms that regulate the expression of
      these neuropeptides. This study shows that melatonin induces the expression of
      fGRP and fGRP-RPs in bullfrogs. Orbital enucleation combined with pinealectomy
      (Ex plus Px) decreased the expression of fGRP precursor mRNA and content of
      mature fGRP and fGRP-RPs in the diencephalon including the SCN and median
      eminence. Conversely, melatonin administration to Ex plus Px bullfrogs increased
      dose-dependently their expressions. The expression of fGRP precursor mRNA was
      photoperiodically controlled and increased under short-day photoperiods, when the
      nocturnal duration of melatonin secretion increases. To clarify the mode of
      melatonin action on the induction of fGRP and fGRP-RPs, we further demonstrated
      the expression of Mel(1b), a melatonin receptor subtype, in SCN neurons
      expressing fGRP precursor mRNA. Finally, we investigated circulating GH and PRL
      levels after melatonin manipulation because fGRP and fGRP-RP-2 stimulate the
      release of GH and GH/PRL, respectively. Ex plus Px decreased plasma GH and PRL
      concentrations, whereas melatonin administration increased these hormone levels.
      These results suggest that melatonin induces the expression of fGRP and fGRP-RP
      2, thus stimulating the release of GH and PRL in bullfrogs.

PMID- 18063681
TI  - Astressin B, a nonselective corticotropin-releasing hormone receptor antagonist,
      prevents the inhibitory effect of ghrelin on luteinizing hormone pulse frequency
      in the ovariectomized rhesus monkey.
AB  - Administration of ghrelin, a key peptide in the regulation of energy homeostasis,
      has been shown to decrease LH pulse frequency while concomitantly elevating
      cortisol levels. Because increased endogenous CRH release in stress is associated
      with an inhibition of reproductive function, we have tested here whether the
      pulsatile LH decrease after ghrelin may reflect an activated hypothalamic
      pituitary-adrenal axis and be prevented by a CRH antagonist. After a 3-h baseline
      LH pulse frequency monitoring, five adult ovariectomized rhesus monkeys received
      a 5-h saline (protocol 1) or ghrelin (100-microg bolus followed by 100 microg/h,
      protocol 2) infusion. In protocols 3 and 4, animals were given astressin B, a
      nonspecific CRH receptor antagonist (0.45 mg/kg im) 90 min before ghrelin or
      saline infusion. Blood samples were taken every 15 min for LH measurements,
      whereas cortisol and GH were measured every 45 min. Mean LH pulse frequency
      during the 5-h ghrelin infusion was significantly lower than in all other
      treatments (P < 0.05) and when compared with the baseline period (P < 0.05).
      Pretreatment with astressin B prevented the decrease. Ghrelin stimulated cortisol
      and GH secretion, whereas astressin B pretreatment prevented the cortisol, but
      not the GH, release. Our data indicate that CRH release mediates the inhibitory
      effect of ghrelin on LH pulse frequency and suggest that the inhibitory impact of
      an insufficient energy balance on reproductive function may in part be mediated
      by the hypothalamic-pituitary-adrenal axis.

PMID- 18063682
TI  - The cooperative effect of growth and differentiation factor-9 and bone
      morphogenetic protein (BMP)-15 on granulosa cell function is modulated primarily
      through BMP receptor II.
AB  - Growth and differentiation factor 9 (GDF9) and bone morphogenetic protein 15
      (BMP15, GDF9B) are oocyte-derived proteins essential for the growth and function
      of ovarian follicles. Moreover, ovine (o) GDF9 and oBMP15 cooperate to increase
      both (3)H-thymidine incorporation and alpha-inhibin production and to inhibit
      progesterone production by rat or ovine granulosa cells. Although the receptors
      through which these proteins act individually have been determined, the
      receptor(s) involved in mediating the cooperative effects of GDF9 and BMP15 is
      (are) unknown. In this study, the effects of the extracellular domains of the
      types I and II TGFbeta receptors on (3)H-thymidine incorporation by rat granulosa
      cells stimulated by oGDF9 and oBMP15 were investigated. Stimulation of (3)H
      thymidine incorporation was completely blocked by the BMP receptor II (BMPRII)
      extracellular domain but unaffected by any other type II or any type I receptor.
      These results suggest that the initial interaction of oGDF9 and oBMP15 is with
      BMPRII and that a type I receptor is either recruited or already associated with
      BMPRII to mediate the cooperative effects of these growth factors.

PMID- 18063683
TI  - Human chorionic gonadotropin stimulates trophoblast invasion through
      extracellularly regulated kinase and AKT signaling.
AB  - Chorionic gonadotropin (CG) is indispensable for human pregnancy because it
      controls implantation, decidualization, and placental development. However, its
      particular role in the differentiation process of invasive trophoblasts has not
      been fully unraveled. Here we demonstrate that the hormone promotes trophoblast
      invasion and migration in different trophoblast model systems. RT-PCR and Western
      blot analyses revealed expression of the LH/CG receptor in trophoblast cell lines
      and different trophoblast primary cultures. In vitro, CG increased migration and
      invasion of trophoblastic SGHPL-5 cells through uncoated and Matrigel-coated
      transwells, respectively. The hormone also increased migration of first-trimester
      villous explant cultures on collagen I. Proliferation of the trophoblast cell
      line and villous explant cultures measured by cumulative cell numbers and in situ
      5-bromo-2'-deoxyuridine labeling, respectively, was unaffected by CG. Addition of
      the hormone activated ERK-1/2 and AKT in SGHPL-5 cells and pure, extravillous
      trophoblasts. Inhibition of MAPK kinase/ERK and phosphatidylinositide 3
      kinase/AKT blocked phosphorylation of the kinases and attenuated CG-dependent
      invasion of SGHPL-5 cells. Similarly, the inhibitors decreased hormone-stimulated
      migration in villous explant cultures. Western blot analyses and gelatin
      zymography suggested that CG increased matrix metalloproteinase (MMP)-2 protein
      levels and activity in both culture systems. Inhibition of ERK or AKT diminished
      CG-induced MMP-2 expression. In summary, the data demonstrate that CG promotes
      trophoblast invasion and migration through activation of ERK and AKT signaling
      involving their downstream effector MMP-2. Because the increase of CG during the
      first trimester of pregnancy correlates with rising trophoblast motility, the
      hormone could be a critical regulator of the early invasion process.

PMID- 18063684
TI  - Activation of SRC kinase and phosphorylation of signal transducer and activator
      of transcription-5 are required for decidual transformation of human endometrial
      stromal cells.
AB  - Progesterone induces decidual transformation of estrogen-primed human endometrial
      stromal cells (hESCs), critical for implantation and maintenance of pregnancy,
      through activation of many signaling pathways involving protein kinase A and
      signal transducer and activator of transcription (STAT)-5. We have previously
      shown that kinase activation of v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene
      homolog (SRC) kinase is closely associated with decidualization and that SRC is
      indispensable for maximal decidualization in mice. To address whether SRC kinase
      activity is essential for decidualization in humans, hESCs were infected with
      adenoviruses carrying enhanced green fluorescent protein alone (Ad-EGFP), a
      kinase-inactive dominant-negative mutant (Ad-SRC/K295R), or an inactive
      autophosphorylation site mutant (Ad-SRC/Y416F). The cells were cultured in the
      presence of estradiol and progesterone (EP) to induce decidualization and
      subjected to RT-PCR, immunoblot, and ELISA analyses. Ad-EGFP-infected hESCs
      exhibited decidual transformation and up-regulation of decidualization markers
      including IGF binding protein 1 and prolactin in response to 12-d treatment with
      EP. In contrast, hESCs infected with Ad-SRC/K295R remained morphologically
      fibroblastoid without production of IGF binding protein 1 and prolactin even
      after EP treatment. Ad-SRC/Y416F displayed similar but less inhibitory effects on
      decidualization, compared with Ad-SRC/K295R. During decidualization, STAT5 was
      phosphorylated on tyrosine 694, a well-known SRC phosphorylation site.
      Phosphorylation was markedly attenuated by Ad-SRC/K295R but not Ad-EGFP. These
      results indicate that the SRC-STAT5 pathway is essential for decidualization of
      hESCs.

PMID- 18063685
TI  - Exendin-4 modulates diabetes onset in nonobese diabetic mice.
AB  - Activation of the glucagon-like peptide-1 receptor (GLP-1R) is associated with
      expansion of beta-cell mass due to stimulation of cell proliferation and
      induction of antiapoptotic pathways coupled to beta-cell survival. Although the
      GLP-1R agonist Exenatide (exendin-4) is currently being evaluated in subjects
      with type 1 diabetes, there is little information available about the efficacy of
      GLP-1R activation for prevention of experimental type 1 diabetes. We examined the
      consequences of exendin-4 (Ex-4) administration (100 ng once daily and 2 microg
      twice daily) on diabetes onset in nonobese diabetic mice beginning at either 4 or
      9 wk of age prior to the onset of diabetes. Ex-4 treatment for 26 wk (2 microg
      twice daily) initiated at 4 wk of age delayed the onset of diabetes (P = 0.007).
      Ex-4-treated mice also exhibited a significant reduction in insulitis scores,
      enhanced beta-cell mass, and improved glucose tolerance. Although GLP-1R mRNA
      transcripts were detected in spleen, thymus, and lymph nodes from nonobese
      diabetic mice, Ex-4 treatment was not associated with significant changes in the
      numbers of CD4+ or CD8+ T cells or B cells in the spleen. However, Ex-4 treatment
      resulted in an increase in the number of CD4+ and CD8+ T cells in the lymph nodes
      and a reduction in the numbers of CD4+CD25+Foxp3+ regulatory T cells in the
      thymus but not in lymph nodes. These findings demonstrate that sustained GLP-1R
      activation in the absence of concomitant immune intervention may be associated
      with modest but significant delay in diabetes onset in a murine model of type 1
      diabetes.

PMID- 18063686
TI  - Induction of central leptin resistance in hyperphagic pseudopregnant rats by
      chronic prolactin infusion.
AB  - Pregnancy in rats is associated with hyperphagia, increased fat deposition, and
      elevated plasma leptin concentrations. Elevated leptin would be expected to
      inhibit food intake, but hypothalamic leptin resistance develops around
      midpregnancy, allowing hyperphagia to be maintained and excess energy to be
      stored as fat in preparation for future metabolic demands of lactation. To
      investigate the hormonal mechanisms inducing leptin resistance during pregnancy,
      the anorectic response to leptin was examined during pseudopregnancy.
      Pseudopregnant rats have identical hormonal profiles to early pregnancy, but no
      placenta formation, allowing differentiation of maternal and placental hormone
      effects on appetite. To investigate the effect of leptin on food intake, d-9
      pseudopregnant rats were injected with leptin (4 microg) via an
      intracerebroventricular (icv) cannula, and then food intake was measured 24 h
      later. Pseudopregnant rats were hyperphagic but had normal anorectic responses to
      leptin. We therefore hypothesized that a longer exposure time to high
      concentrations of progesterone might be required to mimic the leptin resistance
      that occurs on d 14 of pregnancy. Pseudopregnant rats were given progesterone to
      prolong pseudopregnancy beyond the time that leptin resistance develops during
      pregnancy. However, rats remained responsive to icv leptin. To model the
      placental lactogen secretion that occurs during pregnancy, pseudopregnant rats
      were given progesterone and chronic icv ovine prolactin infusion. Central icv
      injection of leptin had no effect on food intake in pseudopregnant rats receiving
      chronic ovine prolactin. These results suggest that chronically high lactogen
      levels, secreted by the placenta during the second half of pregnancy, induce
      central leptin resistance.

PMID- 18063687
TI  - Expression of interferon (IFN)-stimulated genes in extrauterine tissues during
      early pregnancy in sheep is the consequence of endocrine IFN-tau release from the
      uterine vein.
AB  - The ruminant conceptus synthesizes and secretes interferon (IFN)-tau, which
      presumably acts via an intrauterine paracrine mechanism to signal maternal
      recognition of pregnancy. The aims of this study were to determine whether IFN
      stimulated genes (ISG) such as ISG15 and OAS-1 are differentially expressed in
      blood cells circulating in the uterus of ewes; whether extrauterine components of
      the reproductive tract such as the corpus luteum (CL) also express mRNA for these
      ISG, and whether antiviral activity is greater in uterine vein than in uterine
      artery during early pregnancy. The concentrations of mRNA for both ISG were
      significantly greater (P < 0.0001) in endometrium and jugular blood of 15-d
      pregnant ewes than in nonpregnant ewes. ISG15 and OAS-1 mRNA concentrations were
      also greater (P < 0.05) in CL from 15-d pregnant ewes than in nonpregnant ewes.
      Immunohistochemistry revealed intense staining for ISG15 in large luteal cells on
      d 15 of pregnancy. Blood cells from uterine artery and vein of 15-d pregnant ewes
      had similar ISG15 and OAS-1 mRNA concentrations, suggesting that these cells were
      not conditioned by IFN-tau within the uterus. By using an antiviral assay,
      uterine venous blood was found to contain 500- to 1000-fold higher concentrations
      of bioactive IFN-tau than in uterine arterial blood on d 15 of pregnancy. It is
      concluded that uterine vein releases IFN-tau, which induces ISG in extrauterine
      tissues such as the CL during the time of maternal recognition of pregnancy.

PMID- 18063688
TI  - Nuclear receptor agonists improve insulin responsiveness in cultured
      cardiomyocytes through enhanced signaling and preserved cytoskeletal
      architecture.
AB  - Insulin resistance is the failure of insulin to stimulate the transport of
      glucose into its target cells. A highly regulatable supply of glucose is
      important for cardiomyocytes to cope with situations of metabolic stress. We
      recently observed that isolated adult rat cardiomyocytes become insulin resistant
      in vitro. Insulin resistance is combated at the whole body level with agonists of
      the nuclear receptor complex peroxisome proliferator-activated receptor gamma
      (PPARgamma)/retinoid X receptor (RXR). We investigated the effects of
      PPARgamma/RXR agonists on the insulin-stimulated glucose transport and on insulin
      signaling in insulin-resistant adult rat cardiomyocytes. Treatment of
      cardiomyocytes with ciglitazone, a PPARgamma agonist, or 9-cis retinoic acid
      (RA), a RXR agonist, increased insulin- and metabolic stress-stimulated glucose
      transport, whereas agonists of PPARalpha or PPARbeta/delta had no effect.
      Stimulation of glucose transport in response to insulin requires the
      phosphorylation of the signaling intermediate Akt on the residues Thr308 and
      Ser473 and, downstream of Akt, AS160 on several Thr and Ser residues.
      Phosphorylation of Akt and AS160 in response to insulin was lower in insulin
      resistant cardiomyocytes. However, treatment with 9-cis RA markedly increased
      phosphorylation of both proteins. Treatment with 9-cis RA also led to better
      preservation of microtubules in cultured cardiomyocytes. Disruption of
      microtubules in insulin-responsive cardiomyocytes abolished insulin-stimulated
      glucose transport and reduced phosphorylation of AS160 but not Akt. Metabolic
      stress-stimulated glucose transport also involved AS160 phosphorylation in a
      microtubule-dependent manner. Thus, the stimulation of glucose uptake in response
      to insulin or metabolic stress is dependent in cardiomyocytes on the presence of
      intact microtubules.

PMID- 18063689
TI  - Impairment of the natriuretic peptide system in follitropin receptor knockout
      mice and reversal by estradiol: implications for obesity-associated hypertension
      in menopause.
AB  - Estrogen is considered a major regulator of adipose tissue in females. Estrogen
      increases circulating levels of atrial natriuretic peptide (ANP), a hormone with
      renal and cardiovascular effects. The aim of this study was to determine the
      status of the natriuretic peptide system in female follitropin-receptor knockout
      (FORKO) mice that could be associated with obesity and hypertension observed in
      these mutants. Furthermore, estradiol treatment was used to reverse alterations
      observed. FORKO and wild-type (WT) mice received daily injections of estradiol
      for 4 d. On the fifth day, blood was collected for determination of plasma ANP
      levels, and selected tissues were collected for determination of ANP, natriuretic
      peptide receptor type-A (NPR-A) and type-C (NPR-C) gene expression by RT-PCR and
      binding of [(125)I]ANP by autoradiography. At 5 months of age, FORKO mice were
      heavier and had more adipose tissue than WT mice. FORKO mice had lower plasma ANP
      levels and atrial ANP gene expression and higher renal and adipocyte NPR-C gene
      expression than WT mice. Estradiol treatment reduced weight gain and increased
      atrial ANP synthesis as well as decreased ANP clearance NPR-C receptors,
      resulting in elevation of circulating ANP level. In conclusion, this study shows
      that FORKO females have an impaired natriuretic peptide system, which may
      contribute to the susceptibility of FORKO mice to developing age-related
      hypertension previously shown in these animals. This study establishes a relation
      between estrogen, adipose tissue, and ANP, which may have important implications
      in menopausal women.

PMID- 18063690
TI  - Cell-specific activation of the human skeletal alpha-actin by androgens.
AB  - Although it is evident that androgens increase muscle mass and strength, little
      is known about the critical molecular targets of androgens in skeletal muscle. In
      rodents, the skeletal alpha-actin gene is a tissue-specific gene expressed only
      in the levator ani and other skeletal muscles but not in the prostate or
      preputial gland, the well-known androgen target tissue. We identified tissue
      specific androgen-regulated genes in the skeletal muscle in rats after oral
      administration of androgens and focused on androgen-dependent up-regulation of
      the skeletal alpha-actin gene. To investigate the mechanism of action, an in
      vitro system with various cell lines and a series of deletion mutants of the
      alpha-actin promoter were used. The human skeletal alpha-actin promoter was
      activated by androgens in the muscle cell line C2C12 but not in the liver,
      prostate, or breast cancer cell lines in which exogenous human androgen receptor
      is expressed. The sequence of the promoter is sufficient for cell-specific
      androgen response, providing a model for the tissue specificity demonstrated in
      vivo. Using a series of deletion mutants, the androgen response can be maintained
      using just the proximal promoter region. The importance of androgen regulation of
      this small portion of the human skeletal alpha-actin promoter was demonstrated by
      the correlation between muscle and the alpha-actin promoter activity for an array
      of selective androgen receptor modulators (SARMs), including an orally active
      SARM LGD2226. Taken together, the results suggest that the regulation of skeletal
      alpha-actin by androgens/SARMs may represent an important model system for
      understanding androgen anabolic action in the muscle.

PMID- 18063691
TI  - Cooperative binding of insulin-like Peptide 3 to a dimeric relaxin family peptide
      receptor 2.
AB  - Insulin-like peptide 3 (INSL3) binds to a G protein-coupled receptor (GPCR)
      called relaxin family peptide receptor 2 (RXFP2). RXFP2 belongs to the leucine
      rich repeat-containing subgroup (LGR) of class A GPCRs. Negative cooperativity
      has recently been demonstrated in other members of the LGR subgroup. In this
      work, the kinetics of INSL3 binding to HEK293 cells stably transfected with RXFP2
      (HEK293-RXFP2) have been investigated in detail to study whether negative
      cooperativity occurs and whether this receptor functions as a dimer. Our results
      show that negative cooperativity is present and that INSL3-RXFP2 binding shows
      both similarities and differences with insulin binding to the insulin receptor. A
      dose-response curve for the negative cooperativity of INSL3 binding had a reverse
      bell shape reminiscent of that seen for the negative cooperativity of insulin
      binding to its receptor. This suggests that binding of INSL3 may happen in a
      trans rather than in a cis way in a receptor dimer. Bioluminescence resonance
      energy transfer (BRET(2)) experiments confirmed that RXFP2 forms constitutive
      homodimers. Heterodimerization between RXFP2 and RXFP1 was also observed.

PMID- 18063692
TI  - GPR30 contributes to estrogen-induced thymic atrophy.
AB  - The mechanisms by which prolonged estrogen exposures, such as estrogen therapy
      and pregnancy, reduce thymus weight, cellularity, and CD4 and CD8 phenotype
      expression, have not been well defined. In this study, the roles played by the
      membrane estrogen receptor, G protein-coupled receptor 30 (GPR30), and the
      intracellular estrogen receptors, estrogen receptor alpha (ERalpha) and beta
      (ERbeta), in 17beta-estradiol (E2)-induced thymic atrophy were distinguished by
      construction and the side-by-side comparison of GPR30-deficient mice with ERalpha
      and ERbeta gene-deficient mice. Our study shows that whereas ERalpha mediated
      exclusively the early developmental blockage of thymocytes, GPR30 was
      indispensable for thymocyte apoptosis that preferentially occurs in T cell
      receptor beta chain(-/low) double-positive thymocytes. Additionally, G1, a
      specific GPR30 agonist, induces thymic atrophy and thymocyte apoptosis, but not
      developmental blockage. Finally, E2 treatment attenuates the activation of
      nuclear factor-kappa B in CD25(-)CD4(-)CD8(-) double-negative thymocytes through
      an ERalpha-dependent yet ERbeta- and GPR30-independent pathway. Differential
      inhibition of nuclear factor-kappaB by ERalpha and GPR30 might underlie their
      disparate physiological effects on thymocytes. Our study distinguishes, for the
      first time, the respective contributions of nuclear and membrane E2 receptors in
      negative regulation of thymic development.

PMID- 18063693
TI  - Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha
      and -gamma transcriptional activity through a synergy control motif.
AB  - Interplay between different posttranslational modifications of transcription
      factors is an important mechanism to achieve an integrated regulation of gene
      expression. For the estrogen-related receptors (ERRs) alpha and gamma, regulation
      by posttranslational modifications is still poorly documented. Here we show that
      transcriptional repression associated with the ERR amino-terminal domains is
      mediated through sumoylation at a conserved phospho-sumoyl switch, psiKxEPxSP,
      that exists within a larger synergy control motif. Arginine substitution of the
      sumoylatable lysine residue or alanine substitution of a nearby phosphorylatable
      serine residue (serine 19 in ERRalpha) increased the transcriptional activity of
      both ERRalpha and -gamma. In addition, phospho-mimetic substitution of the serine
      residue with aspartate restored the sumoylation and transcriptional repression
      activity. The increased transcriptional activity of the sumoylation-deficient
      mutants was more pronounced in the presence of multiple adjacent ERR response
      elements. We also identified protein inhibitor of activated signal transducer and
      activator of transcription y as an interacting partner and a small ubiquitin
      related modifier E3 ligase for ERRalpha. Importantly, analysis with a phospho
      specific antibody revealed that sumoylation of ERRalpha in mouse liver requires
      phosphorylation of serine 19. Taken together, these results show that the
      interplay of phosphorylation and sumoylation in the amino-terminal domain
      provides an additional mechanism to regulate the transcriptional activity of
      ERRalpha and -gamma.

PMID- 18063695
TI  - The inhibitory collagen receptor LAIR-1 (CD305).
AB  - The immune system protects the body from invaders such as viruses and bacteria.
      Immune cells must be activated in the correct context to function properly. It is
      critical that the receptors, costimulatory molecules, and cytokines that
      orchestrate this activation are carefully regulated to prevent uncontrolled
      inflammation and autoimmunity. Inhibitory receptors play an important role in
      regulation of immune cell function, usually upon interaction with ligands present
      on other cells. In contrast, the function of the inhibitory leukocyte-associated
      Ig-like receptor (LAIR)-1 can be regulated by extracellular matrix collagens.
      LAIR-1 is expressed on most cells of the immune system, and its function has been
      studied on multiple cell types. This review summarizes current literature about
      LAIR-1, a receptor that potentially is able to regulate multiple steps of an
      immune response.

PMID- 18063694
TI  - Receptor activator of nuclear factor-kappaB ligand-induced nuclear factor of
      activated T cells (C1) autoregulates its own expression in osteoclasts and
      mediates the up-regulation of tartrate-resistant acid phosphatase.
AB  - Osteoclasts are large multinucleated, bone-resorbing cells derived from
      hematopoietic precursors in response to receptor activator of nuclear factor
      kappaB ligand (RANKL). RANKL activates a number of signal transduction pathways,
      which stimulate, in turn, a series of specific transcription factors that
      initiate the process of osteoclastogenesis. Perhaps the most important of these
      is nuclear factor of activated T cells cytoplasmic 1 (NFATc1), a DNA-binding
      protein that upon activation translocates to the nucleus where it stimulates
      transcription. The objective of this study was to explore the process whereby
      RANKL induces NFATc1 and to assess the role of this factor in the activation of
      an additional key osteoclast target gene. We found that whereas several NFAT
      members are expressed in RAW264.7 cells, soluble RANKL-induced up-regulation is
      limited to NFATc1 through a mechanism that is largely autoregulatory. Thus,
      although we observed the presence of resident NFAT members at the inducible
      Nfatc1 P1 promoter at very early times after RANKL treatment, a selective and
      time-dependent increase in the binding of up-regulated NFATc1 to Nfatc1 was
      observed beginning at 12 h. Several additional factors that are activated by
      soluble RANKL and also participate in NFATc1 up-regulation include c-Fos and RNA
      polymerase II. Chromatin immunoprecipitation analysis also revealed a similar,
      time-dependent accumulation of NFATc1 at multiple sites on the Acp5 promoter,
      thereby highlighting a central contributing role for NFATc1 in the activation of
      this gene as well. Our studies provide additional molecular detail regarding the
      mechanisms through which RANKL induces NFATc1 in osteoclast precursors and into
      mechanisms by which NFATc1 induces the expression of at least one gene
      responsible for the osteoclast phenotype.

PMID- 18063697
TI  - TNF-related apoptosis-inducing ligand (TRAIL) is expressed throughout myeloid
      development, resulting in a broad distribution among neutrophil granules.
AB  - TRAIL induces apoptosis in a variety of tumor cells. Our laboratory found that
      human neutrophils contain an intracellular reservoir of prefabricated TRAIL that
      is released after stimulation with Mycobacterium bovis bacillus Calmette-Guerin.
      In this study, we examined the subcellular distribution of TRAIL in freshly
      isolated neutrophils. Neutrophil granules, secretory vesicles (SV), and plasma
      membrane vesicles were isolated by subcellular fractionation, followed by free
      flow electrophoresis, and examined by ELISA and immunoblot. TRAIL was found in
      all membrane-bound fractions with the highest amounts in the fractions enriched
      in azurophilic granule (AG) and SV. Immunofluorescence confocal microscopy showed
      that TRAIL colocalized independently with myeloperoxidase (MPO), lactoferrin
      (LF), and albumin, respective markers of AG, specific granules, and SV.
      Furthermore, immunotransmission electron microscopy demonstrated that TRAIL
      colocalized intracellularly with MPO and albumin. We examined TRAIL expression in
      PLB-985 cells induced with dimethylformamide and in CD34-positive stem cells
      treated with G-CSF. Quantitative RT-PCR analysis showed that TRAIL was expressed
      in each stage of development, whereas MPO and LF were only expressed at distinct
      times during differentiation. Collectively, these findings suggest that TRAIL is
      expressed throughout neutrophil development, resulting in a broad distribution
      among different granule subtypes.

PMID- 18063696
TI  - Gammadelta T cells mitigate the organ injury and mortality of sepsis.
AB  - Sepsis is a difficult condition to treat and is associated with a high mortality
      rate. Sepsis is known to cause a marked depletion of lymphocytes, although the
      function of different lymphocyte subsets in the response to sepsis is unclear.
      gammadelta T cells are found largely in epithelial-rich tissues, and previous
      studies of gammadelta T cells in models of sepsis have yielded divergent results.
      In the present study, we examined the function of gammadelta T cells during
      sepsis in mice using cecal ligation and puncture (CLP). Mice deficient in
      gammadelta T cells had decreased survival times and increased tissue damage after
      CLP compared with wild-type mice. Furthermore, bacterial load was increased in
      gammadelta T cell-deficient mice, yet antibiotic treatment did not change
      mortality. Additionally, we found that recruitment of neutrophils and myeloid
      suppressor cells to the site of infection was diminished in gammadelta T cell
      deficient mice. Finally, we found that circulating levels of IFN-gamma were
      increased, and systemic levels of IL-10 were decreased in gammadelta T cell
      deficient mice after CLP compared with wild-type mice. gammadelta T cell
      deficient mice also had increased intestinal permeability after CLP compared with
      wild-type mice. Neutralization of IFN-gamma abrogated the increase in intestinal
      permeability in gammadelta T cell-deficient mice. The intestines taken from
      gammadelta T cell-deficient mice had decreased myeloperoxidase yet had increased
      tissue damage as compared with wild-type mice. Collectively, our data suggest
      that gammadelta T cells modulate the response to sepsis and may be a potential
      therapeutic target.

PMID- 18063698
TI  - Intravascular inactivation of CCR5 by n-Nonanoyl-CC chemokine ligand 14 and
      inhibition of allergic airway inflammation.
AB  - Modulation of leukocyte recruitment through intervention with chemokine receptors
      is an attractive, therapeutic strategy. Recently, we have shown that n-Nonanoyl
      (NNY)-CCL14 internalizes and desensitizes human (h)CCR3, resulting in the
      inactivation of eosinophils. In this study, we investigated the interaction of
      NNY-CCL14 with CCR1 and CCR5 and the relevance of these NNY-CCL14 receptors on
      its in vivo effects in allergic airway inflammation. NNY-CCL14 has inactivating
      properties on CCR1(+) and CCR5(+) cell lines and primary leukocytes. It
      desensitizes hCCR1- and hCCR5-mediated calcium release and internalizes these
      receptors from the cellular surface. Treatment of OVA-sensitized BALB/c mice with
      NNY-CCL14 resulted in reduced pulmonary inflammation. Above all, it is
      demonstrated that systemic treatment with NNY-CCL14 down-modulates CCR5 from the
      surface of lymphocytes in vivo. Although NNY-CCL14 acts on murine lymphocytes and
      internalizes CCR5, it does not internalize CCR3 on mouse eosinophils, showing
      species selectivity regarding this particular receptor. Therefore, the inhibitory
      effects of NNY-CCL14 in murine models of allergic airway inflammation can be
      assigned to its interaction with CCR5. The presented results substantiate the
      relevance of CCR5 as a target for allergic airway inflammation.

PMID- 18063699
TI  - Functions of C2D macrophage cells after adoptive transfer.
AB  - Macrophage function depends on their in situ location. To test this hypothesis,
      we examined functional changes of the C2D macrophage cell line after adoptive
      transfer. In vitro, C2D macrophages reside early in the macrophage lineage and
      show little functional activity. After in vivo i.p. culture, C2D macrophage cells
      switch their cytokine/chemokine profile from primarily Th2 cytokines produced in
      vitro to a Th1 profile including MIP-1alpha, IL-6, and TNF-alpha. The in vivo
      environment also caused C2D macrophage cells to become more phagocytic than their
      in vitro counterparts. These data indicate that C2D macrophage cells exhibit
      distinct functions because of in vivo signals that are absent during in vitro
      culture.

PMID- 18063700
TI  - Interleukin-17--extended features of a key player in multiple sclerosis.

PMID- 18063701
TI  - Exaggerated neointima formation in human C-reactive protein transgenic mice is
      IgG Fc receptor type I (Fc gamma RI)-dependent.
AB  - Neointima formation after vascular injury is exaggerated in ovariectomized (OVX)
      human C-reactive protein transgenic mice (CRPtg) compared to nontransgenic mice
      (NTG). We tested the hypothesis that this CRP-mediated exacerbation requires IgG
      Fc receptors (Fc gamma Rs). OVX NTG, CRPtg, and CRPtg lacking Fc gamma RI, Fc
      gamma RIIb, Fc gamma RIII, or the common gamma chain (FcR gamma) had their common
      carotid artery ligated. Twenty-eight days later neointimal thickening in CRPtg/Fc
      gamma RI(-/-) and CRPtg/FcR gamma (-/-) was significantly less than in CRPtg and
      no worse than in NTG, whereas in CRPtg/Fc gamma RIIb(-/-) and CRPtg/Fc gamma
      RIII(-/-) neointimal thickness was equal to or greater than in CRPtg.
      Immunohistochemistry revealed human CRP in the neointima of CRPtg, but little or
      none was observed in those lacking Fc gamma RI or FcR gamma. Real-time reverse
      transcriptase-polymerase chain reaction demonstrated that Fc gamma R types I to
      III were expressed in the CRPtg arteries, with Fc gamma RI expression increasing
      by threefold after ligation injury. Levels of serum complement (C3), neointimal
      deposition of complement (C3d), and cellular composition (monocytes, macrophages,
      lymphocytes) in the neointima did not differ among the different CRPtg genotypes.
      However, by immunofluorescence a neointimal population of F4/80+CRP+ cells was
      revealed only in OVX CRPtg. The exaggerated response to vascular injury provoked
      by CRP in OVX CRPtg depends on Fc gamma RI and probably requires its expression
      by F4/80+ cells.

PMID- 18063703
TI  - Purinergic receptors in gastrointestinal inflammation.
AB  - Purinergic receptors comprise a family of transmembrane receptors that are
      activated by extracellular nucleosides and nucleotides. The two major classes of
      purinergic receptors, P1 and P2, are expressed widely in the gastrointestinal
      tract as well as immune cells. The purinergic receptors serve a variety of
      functions from acting as neurotransmitters, to autocoid and paracrine signaling,
      to cell activation and immune response. Nucleosides and nucleotide agonist of
      purinergic receptors are released by many cell types in response to specific
      physiological signals, and their levels are increased during inflammation. In the
      past decade, the advent of genetic knockout mice and the development of highly
      potent and selective agonists and antagonists for the purinergic receptors have
      significantly advanced the understanding of purinergic receptor signaling in
      health and inflammation. In fact, agonist/antagonists of purinergic receptors are
      emerging as therapeutic modalities to treat intestinal inflammation. In this
      article, the distribution of the purinergic receptors in the gastrointestinal
      tract and their physiological and pathophysiological role in intestinal
      inflammation will be reviewed.

PMID- 18063704
TI  - Liver sinusoidal endothelial cells are the principal site for elimination of
      unfractionated heparin from the circulation.
AB  - The mechanism of elimination of blood borne heparin was studied. To this end
      unfractionated heparin (UFH) was tagged with FITC, which served as both a visual
      marker and a site of labeling with (125)I-iodine. UFH labeled in this manner did
      not alter the anticoagulant activity or binding specificity of the
      glycosaminoglycan. Labeled heparin administered intravenously to rats (0.1 IU/kg)
      had a circulatory t(1/2) of 1.7 min, which was increased to 16 min upon
      coinjection with unlabeled UFH (100 IU/kg). At 15 min after injection, 71% of
      recovered radioactivity was found in liver. Liver cell separation revealed the
      following relative uptake capacity, expressed per cell: liver sinusoidal
      endothelial cell (LSEC)-parenchymal cell-Kupffer cell = 15:3.6:1. Fluorescence
      microscopy on liver sections showed accumulation of FITC-UFH only in cells lining
      the liver sinusoids. No fluorescence was detected in parenchymal cells or
      endothelial cells lining the central vein. Fluorescence microscopy of cultured
      LSECs following binding of FITC-UFH at 4 degrees C and chasing at 37 degrees C,
      showed accumulation of the probe in vesicles located at the periphery of the
      cells after 10 min, with transfer to large, evenly stained vesicles in the
      perinuclear region after 2 h. Immunogold electron microscopy of LSECs to probe
      the presence of FITC following injection of FITC-UFH along with BSA-gold to mark
      lysosomes demonstrated colocalization of the probe with the gold particles in the
      lysosomal compartment. Receptor-ligand competition experiments in primary
      cultures of LSECs indicated the presence of a specific heparin receptor,
      functionally distinct from the hyaluronan/scavenger receptor (Stabilin2). The
      results suggest a major role for LSECs in heparin elimination.

PMID- 18063702
TI  - Sex-defined T-cell responses to cardiac self determine differential outcomes of
      murine dilated cardiomyopathy.
AB  - Idiopathic dilated cardiomyopathy (DCM) is a disease of putative autoimmune
      origin that kills males at a twofold to threefold greater frequency than females.
      The reasons underlying these differential outcomes may be related to sex
      divergent self-recognition. Here we examined sex-specific autoimmune responses to
      cardiac self and their impact on DCM development. We found that males immunized
      to the p406-425 peptide derived from mouse cardiac alpha-myosin heavy chain
      preferentially develop a predominant Th17 lineage response that provides
      sustained T-cell memory and a high DCM incidence whereas females preferentially
      develop a predominant Th1 lineage response that becomes anergized to cardiac self
      resulting in compensatory protection against DCM. The distinct sex-defined
      disease phenotypes are interchangeable after in vivo manipulation of Th1
      (interleukin-2) and Th17 (interleukin-17) cytokines. Our study shows that male
      and female SWXJ mice differentially respond to cardiac self in ways that lead to
      distinct autoimmune outcomes and implies that optimized therapy for autoimmunity
      may require consideration of the qualitatively different ways that males and
      females engage self.

PMID- 18063705
TI  - The adventures of Sonic Hedgehog in development and repair. I. Hedgehog signaling
      in gastrointestinal development and disease.
AB  - Hedgehog (Hh) proteins are members of a family of secreted signaling factors that
      orchestrate the development of many organs and tissues including those of the
      gastrointestinal (GI) tract. The requirement for Hh activity is not limited to
      early development but underlies the homeostasis of a number of tissues, and
      abnormal activity of the Hh pathway is associated with several GI malignancies.
      Understanding the roles and mechanisms of action of Hh signaling both in
      development and postnatally should thus give novel insights into potential
      treatments for these diseases. Here we focus on the Hh signaling pathway and its
      role in GI tract development and maintenance and consider the diseases resulting
      from aberrant Hh activity.

PMID- 18063706
TI  - Mechanisms of oxidant production in esophageal squamous cell and Barrett's cell
      lines.
AB  - We hypothesized that differences among individuals in reflux-induced oxidant
      production by esophageal squamous epithelial cells might contribute to the
      development of Barrett's esophagus. We studied the effects of acid and bile acids
      on the production of reactive oxygen species (ROS) in esophageal squamous cell
      lines derived from gastroesophageal reflux disease patients with (NES-B3T) and
      without (NES-G2T) Barrett's esophagus and in a Barrett's epithelial cell line
      (BAR-T). Cells were incubated with an ROS-sensitive probe and exposed to acidic
      medium, neutral bile acid medium, or acidic bile acid medium. ROS were quantified
      in the presence and absence of diphenyleneiodonium chloride (DPI, an NADPH
      oxidase inhibitor), N(G)-monomethyl-l-arginine (l-NMMA, a nitric oxide synthase
      inhibitor), and rotenone (a mitochondrial electron transport chain inhibitor).
      Acidic bile acid medium induced ROS production in both squamous cell lines;
      however, only DPI blocked ROS production by NES-B3T cells, whereas both DPI and l
      NMMA blocked ROS production by NES-G2T cells. In BAR-T cells, acidic medium and
      acidic bile acid medium induced the production of ROS; l-NMMA prevented ROS
      production after exposure to acidic medium, whereas ROS production induced by
      acidic bile acid medium was blocked by DPI. These studies demonstrate that there
      are differences between esophageal squamous cells and Barrett's epithelial cells
      and between esophageal squamous cells from gastroesophageal reflux disease
      patients with and without Barrett's esophagus in the mechanisms of oxidant
      production induced by exposure to acid and bile acids.

PMID- 18063708
TI  - The liver sinusoidal endothelial cell: a cell type of controversial and confusing
      identity.
AB  - A look through the literature on liver sinusoidal endothelial cells (LSECs)
      reveals that there are several conflicts among different authors of what this
      cell type is and does. Major controversies that will be highlighted in this
      review include aspects of the physiological role, the characterization, and the
      protocols of isolation and cultivation of these cells. Many of these conflicts
      may be ascribed to the fact that the cell was only recently established as a
      distinct cell type and that researchers from different disciplines tend to define
      their structure and function differently. This field is in need of a common
      platform to obtain a sound communication and a unified understanding of how to
      interpret novel research results. The aim of this review is to encourage
      scientists not to ignore the fact that there are, indeed, different opinions in
      the literature on LSECs. We also hope that this review will point out to the
      reader that some issues that may seem well established regarding our knowledge
      about the LSECs, in reality, are still unresolved and, indeed, controversial.

PMID- 18063707
TI  - Modulation of ileal bile acid transporter (ASBT) activity by depletion of plasma
      membrane cholesterol: association with lipid rafts.
AB  - Apical sodium-dependent bile acid transporter (ASBT) represents a highly
      efficient conservation mechanism of bile acids via mediation of their active
      transport across the luminal membrane of terminal ileum. To gain insight into the
      cellular regulation of ASBT, we investigated the association of ASBT with
      cholesterol and sphingolipid-enriched specialized plasma membrane microdomains
      known as lipid rafts and examined the role of membrane cholesterol in maintaining
      ASBT function. Human embryonic kidney (HEK)-293 cells stably transfected with
      human ASBT, human ileal brush-border membrane vesicles, and human intestinal
      epithelial Caco-2 cells were utilized for these studies. Floatation experiments
      on Optiprep density gradients demonstrated the association of ASBT protein with
      lipid rafts. Disruption of lipid rafts by depletion of membrane cholesterol with
      methyl-beta-cyclodextrin (MbetaCD) significantly reduced the association of ASBT
      with lipid rafts, which was paralleled by a decrease in ASBT activity in Caco-2
      and HEK-293 cells treated with MbetaCD. The inhibition in ASBT activity by
      MbetaCD was blocked in the cells treated with MbetaCD-cholesterol complexes.
      Kinetic analysis revealed that MbetaCD treatment decreased the V(max) of the
      transporter, which was not associated with alteration in the plasma membrane
      expression of ASBT. Our study illustrates that cholesterol content of lipid rafts
      is essential for the optimal activity of ASBT and support the association of ASBT
      with lipid rafts. These findings suggest a novel mechanism by which ASBT activity
      may be rapidly modulated by alterations in cholesterol content of plasma membrane
      and thus have important implications in processes related to maintenance of bile
      acid and cholesterol homeostasis.

PMID- 18063709
TI  - Workforce analysis in orthopaedic surgery.

PMID- 18063710
TI  - Standards of professionalism on orthopaedist-industry conflicts of interest.

PMID- 18063711
TI  - Minimal incision total hip arthroplasty.
AB  - Although debate regarding minimally invasive hip surgery is inconclusive,
      information published to date on the risks and benefits of small-incision
      approaches focuses the discussion on quality and outcomes. Small-incision
      surgical approaches include the posterior, anterolateral, direct anterior, and
      two-incision approach. Computer navigation assists in mapping hip replacement
      surgery. Obesity is a risk factor and has been found to increase complications.
      Patient education, pain management, and rehabilitation are important to recovery
      after minimal incision hip arthroplasty. Total hip replacement may be
      successfully achieved via smaller incisions, but functional improvement,
      discharge to home, patient satisfaction, and analgesic requirement may be similar
      regardless of the length of the incision.

PMID- 18063712
TI  - Fracture of the femoral head.
AB  - Fracture of the femoral head is a severe, relatively uncommon injury; typically,
      it occurs following traumatic posterior dislocation of the hip joint. The Pipkin
      classification is the most commonly used classification system. Diagnosis is
      aided by a complete history, physical examination, and imaging, including
      computed tomography. Treatment consists of urgent closed reduction of the
      dislocated hip followed by nonsurgical or surgical management of any associated
      fractures. Controversies include the preferred surgical approach (anterior versus
      posterior) and whether to perform femoral head fragment excision or internal
      fixation. Complications associated with fracture of the femoral head and
      subsequent treatment include osteonecrosis, posttraumatic osteoarthritis, and
      heterotopic ossification. Fracture of the femoral head has been associated with a
      relatively poor functional outcome.

PMID- 18063713
TI  - The halo fixator.
AB  - The halo fixator may be used for the definitive treatment of cervical spine
      trauma, preoperative reduction in the patient with spinal deformity, and
      adjunctive postoperative stabilization following cervical spine surgery. Halo
      fixation decreases cervical motion by 30% to 96%. Absolute contraindications
      include cranial fracture, infection, and severe soft-tissue injury at the
      proposed pin sites. Relative contraindications include severe chest trauma,
      obesity, advanced age, and a barrel-shaped chest. In children, a computed
      tomography scan of the head should be obtained before pin placement to determine
      cranial bone thickness. Complications of halo fixation include pin loosening, pin
      site infection, and skin breakdown. A concerning rate of life-threatening
      complications, such as respiratory distress, has been reported in elderly
      patients. Despite a paucity of contemporary data, recent retrospective studies
      have demonstrated acceptable results for halo fixation in managing some upper and
      lower cervical spine injuries.

PMID- 18063714
TI  - The pediatric triplane ankle fracture.
AB  - The pediatric triplane ankle fracture represents a unique spectrum of injury that
      does not fit neatly into the Salter-Harris classification of physeal injury. This
      fracture is particular to the pediatric population and often is termed a
      transitional injury. It is the result of the characteristic asymmetric closure of
      the distal tibial physis over a period of approximately 18 months. The triplane
      ankle fracture is a multiplanar injury with three classically described fracture
      fragments. It has several variations and represents 5% to 10% of pediatric intra
      articular ankle injuries. The fracture typically presents in children aged 12 to
      15 years; incidence is slightly higher in boys than in girls. Nondisplaced
      triplane fractures and extra-articular fractures can be managed with
      immobilization in a long leg cast. Displaced fractures are treated with open
      reduction and internal fixation performed through an anterolateral approach or an
      anteromedial approach. Intra-articular reduction to within 2 mm is required for
      optimal treatment of these unique pediatric ankle fractures.

PMID- 18063715
TI  - Cycling injuries of the lower extremity.
AB  - Cycling is an increasingly popular recreational and competitive activity, and
      cycling-related injuries are becoming more common. Many common cycling injuries
      of the lower extremity are preventable. These include knee pain, patellar
      quadriceps tendinitis, iliotibial band syndrome, hip pain, medial tibial stress
      syndrome, stress fracture, compartment syndrome, numbness of the foot, and
      metatarsalgia. Injury is caused by a combination of inadequate preparation,
      inappropriate equipment, poor technique, and overuse. Nonsurgical management may
      include rest, nonsteroidal anti-inflammatory drugs, corticosteroid injection,
      ice, a reduction in training intensity, orthotics, night splints, and physical
      therapy. Injury prevention should be the focus, with particular attention to
      bicycle fit and alignment, appropriate equipment, proper rider position and
      pedaling mechanics, and appropriate training.

PMID- 18063716
TI  - De quervain tenosynovitis of the wrist.
AB  - De quervain disease, or stenosing tenosynovitis of the first dorsal compartment
      of the wrist, is a common wrist pathology. Pain results from resisted gliding of
      the abductor pollicis longus and the extensor pollicis brevis tendons in the
      fibro-osseus canal. de Quervain tenosynovitis of the wrist is more common in
      women than men. Diagnosis may be made on physical examination. Radiographs are
      helpful in ruling out offending bony pathology. Nonsurgical management,
      consisting of corticosteroid injections and supportive thumb spica splinting, is
      usually successful. In resistant cases, surgical release of the first dorsal
      compartment is done, taking care to protect the radial sensory nerve and identify
      all accessory compartments. Repair of the extensor retinaculum by step-cut
      lengthening or other techniques is rarely required.

PMID- 18063718
TI  - Function, structure, and evolution of the RubisCO-like proteins and their RubisCO
      homologs.
AB  - About 30 years have now passed since it was discovered that microbes synthesize
      RubisCO molecules that differ from the typical plant paradigm. RubisCOs of forms
      I, II, and III catalyze CO(2) fixation reactions, albeit for potentially
      different physiological purposes, while the RubisCO-like protein (RLP) (form IV
      RubisCO) has evolved, thus far at least, to catalyze reactions that are important
      for sulfur metabolism. RubisCO is the major global CO(2) fixation catalyst, and
      RLP is a somewhat related protein, exemplified by the fact that some of the
      latter proteins, along with RubisCO, catalyze similar enolization reactions as a
      part of their respective catalytic mechanisms. RLP in some organisms catalyzes a
      key reaction of a methionine salvage pathway, while in green sulfur bacteria, RLP
      plays a role in oxidative thiosulfate metabolism. In many organisms, the function
      of RLP is unknown. Indeed, there now appear to be at least six different clades
      of RLP molecules found in nature. Consideration of the many RubisCO (forms I, II,
      and III) and RLP (form IV) sequences in the database has subsequently led to a
      coherent picture of how these proteins may have evolved, with a form III RubisCO
      arising from the Methanomicrobia as the most likely ultimate source of all
      RubisCO and RLP lineages. In addition, structure-function analyses of RLP and
      RubisCO have provided information as to how the active sites of these proteins
      have evolved for their specific functions.

PMID- 18063719
TI  - The autodisplay story, from discovery to biotechnical and biomedical
      applications.
AB  - Among the pathways used by gram-negative bacteria for protein secretion, the
      autotransporter pathway represents a solution of impressive simplicity. Proteins
      are transported, independent of their nature as recombinant or native passengers,
      as long as the coding nucleotide sequence is inserted in frame between those of
      an N-terminal signal peptide and a C-terminal domain, referred to as the beta
      barrel of the outer membrane translocation unit. The immunoglobulin A1 (IgA1)
      protease from Neisseria gonorrhoeae was the first identified member of the
      autotransporter family of secreted proteins. The IgA1 protease was employed in
      initial experiments investigating autotransporter-mediated surface display of
      recombinant proteins and to investigate structural and functional requirements.
      Various other autotransporter proteins have since been described, and the
      autodisplay system was developed on the basis of the natural Escherichia coli
      autotransporter protein AIDA-I (adhesin involved in diffuse adherence).
      Autodisplay has been used for the surface display of random peptide libraries to
      successfully screen for novel enzyme inhibitors. The autodisplay system was also
      used for the surface display of functional enzymes, including esterases,
      oxidoreductases, and electron transfer proteins. Whole E. coli cells displaying
      enzymes have been utilized to efficiently synthesize industrially important rare
      organic compounds with specific chirality. Autodisplay of epitopes on the surface
      of attenuated Salmonella carriers has also provided a novel way to induce immune
      protection after oral vaccination. This review summarizes the structural and
      functional features of the autodisplay system, illustrating its discovery and
      most recent applications. Autodisplay facilitates the export of more than 100,000
      recombinant molecules per single cell and permits the oligomerization of subunits
      on the cell surface as well as the incorporation of inorganic prosthetic groups
      after transport of apoproteins onto the bacterial surface without disturbing
      bacterial integrity or viability. We discuss future biotechnical and biomedical
      applications in the light of these achievements.

PMID- 18063720
TI  - Lipid intermediates in the biosynthesis of bacterial peptidoglycan.
AB  - This review is an attempt to bring together and critically evaluate the now
      abundant but dispersed data concerning the lipid intermediates of the
      biosynthesis of bacterial peptidoglycan. Lipid I, lipid II, and their modified
      forms play a key role not only as the specific link between the intracellular
      synthesis of the peptidoglycan monomer unit and the extracytoplasmic
      polymerization reactions but also in the attachment of proteins to the bacterial
      cell wall and in the mechanisms of action of antibiotics with which they form
      specific complexes. The survey deals first with their detection, purification,
      structure, and preparation by chemical and enzymatic methods. The recent
      important advances in the study of transferases MraY and MurG, responsible for
      the formation of lipids I and II, are reported. Various modifications undergone
      by lipids I and II are described, especially those occurring in gram-positive
      organisms. The following section concerns the cellular location of the lipid
      intermediates and the translocation of lipid II across the cytoplasmic membrane.
      The great efforts made since 2000 in the study of the glycosyltransferases
      catalyzing the glycan chain formation with lipid II or analogues are analyzed in
      detail. Finally, examples of antibiotics forming complexes with the lipid
      intermediates are presented.

PMID- 18063723
TI  - Inhibition of mitochondrial hydrogen peroxide production by lipophilic
      metalloporphyrins.
AB  - Many studies have established a role for oxidative stress and mitochondrial
      dysfunction as an important mechanism in the pathogenesis of neuronal disorders.
      Metalloporphyrins are a class of catalytic antioxidants that are capable of
      detoxifying a wide range of reactive oxygen species. The AEOL112 series of
      glyoxylate metalloporphyrins were designed with increased lipid solubility for
      better oral bioavailability and penetration of the blood-brain barrier. The goal
      of this study was to develop an in vitro assay using rat brain mitochondria to
      reliably detect endogenously released hydrogen peroxide (H(2)O(2)) and identify
      glyoxylate metalloporphyrins based on rank order of potency for removal of
      physiologically relevant H(2)O(2). A polarographic method was established for the
      sensitive, accurate, and reproducible detection of low levels of H(2)O(2). The
      assay identified several potent glyoxylate metalloporphyrins with H(2)O(2)
      scavenging potencies (IC(50)) in the nanomolar range. These results provide a
      simplified in vitro model system to detect physiologically generated
      mitochondrial H(2)O(2) as a screening tool to predict the biological efficacy of
      potential therapeutic entities.

PMID- 18063721
TI  - Manipulation of rab GTPase function by intracellular bacterial pathogens.
AB  - Intracellular bacterial pathogens have evolved highly specialized mechanisms to
      enter and survive within their eukaryotic hosts. In order to do this, bacterial
      pathogens need to avoid host cell degradation and obtain nutrients and
      biosynthetic precursors, as well as evade detection by the host immune system. To
      create an intracellular niche that is favorable for replication, some
      intracellular pathogens inhibit the maturation of the phagosome or exit the
      endocytic pathway by modifying the identity of their phagosome through the
      exploitation of host cell trafficking pathways. In eukaryotic cells, organelle
      identity is determined, in part, by the composition of active Rab GTPases on the
      membranes of each organelle. This review describes our current understanding of
      how selected bacterial pathogens regulate host trafficking pathways by the
      selective inclusion or retention of Rab GTPases on membranes of the vacuoles that
      they occupy in host cells during infection.

PMID- 18063717
TI  - Evolution of the chaperone/usher assembly pathway: fimbrial classification goes
      Greek.
AB  - Many Proteobacteria use the chaperone/usher pathway to assemble proteinaceous
      filaments on the bacterial surface. These filaments can curl into fimbrial or
      nonfimbrial surface structures (e.g., a capsule or spore coat). This article
      reviews the phylogeny of operons belonging to the chaperone/usher assembly class
      to explore the utility of establishing a scheme for subdividing them into clades
      of phylogenetically related gene clusters. Based on usher amino acid sequence
      comparisons, our analysis shows that the chaperone/usher assembly class is
      subdivided into six major phylogenetic clades, which we have termed alpha-, beta
      , gamma-, kappa-, pi-, and sigma-fimbriae. Members of each clade share related
      operon structures and encode fimbrial subunits with similar protein domains. The
      proposed classification system offers a simple and convenient method for
      assigning newly discovered chaperone/usher systems to one of the six major
      phylogenetic groups.

PMID- 18063725
TI  - Life after the EBM workshop.

PMID- 18063727
TI  - Evidence-based case reports.

PMID- 18063724
TI  - Inhibitor binding in the human renal low- and high-affinity Na+/glucose
      cotransporters.
AB  - The kidney contains two Na(+)/glucose cotransporters, called SGLT2 and SGLT1,
      arranged in series along the length of the proximal tubule. The low-affinity
      transporter, SGLT2, is responsible for the reabsorption of most of the glucose in
      the kidney. There is recent interest in SGLT2 as a target for the treatment of
      type II diabetes using selective inhibitors based on the structure of the
      phenylglucoside, phlorizin (phloretin-2'-beta-glucoside). In this study, we
      examined the inhibition of alpha-methyl-d-glucopyranose transport by phlorizin
      and a new candidate drug, sergliflozin-A [(2-[4-methoxyphenyl]methyl)phenyl beta
      d-glucopyranoside], in COS-7 cells expressing hSGLT1 and hSGLT2. Inhibition by
      phlorizin was competitive, with K(i) values of 0.3 muM in hSGLT1 and 39 nM in
      hSGLT2. Inhibition by sergliflozin-A was also competitive, with K(i) values of 1
      muM in hSGLT1 and 20 nM in hSGLT2. Phloretin [3-(4-hydroxyphenyl)-1-(2,4,6
      trihydroxyphenyl)-1-propanone; the aglucone of phlorizin] was a less potent
      inhibitor, with IC(50) values of 142 muM in hSGLT1 and 25 muM in hSGLT2. Site
      directed mutagenesis of residues believed to be in the phlorizin binding site
      showed that only Cys610 is involved in inhibitor binding in the human
      transporters. Mutation of Cys610 in hSGLT1 to lysine resulted in an increased
      IC(50) for all inhibitors. In contrast, mutagenesis of the analogous Cys615 in
      hSGLT2 produced the opposite effect, a decrease in IC(50) for phlorizin and
      sergliflozin-A. The differences in the effects of the mutations between hSGLT1
      and hSGLT2 suggest that this cysteine holds key residues in place rather than
      participating directly in inhibitor binding.

PMID- 18063728
TI  - Review: vaccines against human papillomavirus prevent cervical cancer precursors
      in young women for at least 3 years.

PMID- 18063729
TI  - Review: rosiglitazone increases risk of MI but does not differ from other drugs
      for CV death in type 2 diabetes.

PMID- 18063730
TI  - Rosiglitazone increased heart failure but did not differ from metformin plus
      sulphonylurea for other CV outcomes at interim analysis.

PMID- 18063731
TI  - Review: regular brisk walking improves cardiovascular risk factors in healthy
      sedentary adults.

PMID- 18063722
TI  - Interspecies interactions within oral microbial communities.
AB  - While reductionism has greatly advanced microbiology in the past 400 years,
      assembly of smaller pieces just could not explain the whole! Modern
      microbiologists are learning "system thinking" and "holism." Such an approach is
      changing our understanding of microbial physiology and our ability to
      diagnose/treat microbial infections. This review uses oral microbial communities
      as a focal point to describe this new trend. With the common name "dental
      plaque," oral microbial communities are some of the most complex microbial floras
      in the human body, consisting of more than 700 different bacterial species. For a
      very long time, oral microbiologists endeavored to use reductionism to identify
      the key genes or key pathogens responsible for oral microbial pathogenesis. The
      limitations of reductionism forced scientists to begin adopting new strategies
      using emerging concepts such as interspecies interaction, microbial community,
      biofilms, polymicrobial disease, etc. These new research directions indicate that
      the whole is much more than the simple sum of its parts, since the interactions
      between different parts resulted in many new physiological functions which cannot
      be observed with individual components. This review describes some of these
      interesting interspecies-interaction scenarios.

PMID- 18063732
TI  - Warfarin reduced major stroke more than aspirin in elderly patients with atrial
      fibrillation in primary care.

PMID- 18063733
TI  - Symptomatic use of beclomethasone-albuterol and regular use of beclomethasone did
      not differ for control of mild asthma.

PMID- 18063734
TI  - Induction of labour post-term or expectant management with serial fetal
      monitoring had similar neonatal outcomes.

PMID- 18063735
TI  - Prednisolone plus paracetamol (acetaminophen) was as effective as indomethacin
      plus paracetamol but had fewer adverse effects in acute gout-like arthritis.

PMID- 18063736
TI  - Intranasal fentanyl and intravenous morphine did not differ for pain relief in
      children with closed long-bone fractures.

PMID- 18063737
TI  - Review: on-demand maintenance therapy with proton pump inhibitors is as effective
      as continuous therapy for non-erosive GORD.

PMID- 18063738
TI  - Cleaning of the perineal/genital area before urine collection from toilet-trained
      children prevented sample contamination.

PMID- 18063739
TI  - Review: brief interventions including information sessions, motivational
      interviews, and cognitive behavioural therapy reduce excessive alcohol
      consumption in primary care.

PMID- 18063740
TI  - An intensive lifestyle intervention reduced weight and cardiovascular disease
      risk factors in obese participants with type 2 diabetes at 1 year in an interim
      analysis.

PMID- 18063741
TI  - Irrigation of simple lacerations with tap water or sterile saline in the
      emergency department did not differ for wound infections.

PMID- 18063742
TI  - Review: some screening tests for dementia in older people are accurate and
      practical for use in primary care.

PMID- 18063743
TI  - Review: anti-cyclic citrullinated peptide antibody is a more specific test for
      rheumatoid arthritis than rheumatoid factor.

PMID- 18063744
TI  - Review: increased waist circumference or waist-to-hip ratio is associated with
      increased risk of cardiovascular events.

PMID- 18063745
TI  - Reminders in echocardiography reports increased use of blockers in reduced left
      ventricular ejection fraction.

PMID- 18063746
TI  - Review: evidence from single studies shows that a few fall risk assessment tools
      can predict falls in elderly people.

PMID- 18063747
TI  - The ankle brachial index independently predicted all-cause mortality in high-risk
      patients with peripheral arterial disease.

PMID- 18063748
TI  - Community reintegration of ex-prisoners: type and degree of change in variables
      influencing successful reintegration.
AB  - Community reintegration of ex-prisoners is an important issue in efforts to
      reduce recidivism. The present study examined the multiple, complex, and dynamic
      nature of variables influencing successful reintegration by assessing the type
      and degree of change in reintegration variables over time. Participants were 79
      adult prisoners (54 male, 25 female) who completed a prerelease questionnaire 1
      month before their release, which focused on prison-related variables,
      participant background, and anticipated conditions upon release. A postrelease
      questionnaire was administered to the same participants at 1-4 weeks and 3-4
      months postrelease, focusing on the quality of life conditions experienced
      following release. Results indicate that current health ratings and several
      indicators of drug use were significantly different over the three measurement
      phases. Ratings of employment and housing stability, finance, and social support
      were unchanged over the postrelease period. Theoretical implications of the
      present investigation for reintegration theory are discussed, together with
      practical applications.

PMID- 18063749
TI  - alphaB-crystallin promotes tumor angiogenesis by increasing vascular survival
      during tube morphogenesis.
AB  - Selective targeting of endothelial cells in tumor vessels requires delineation of
      key molecular events in formation and survival of blood vessels within the tumor
      microenvironment. To this end, proteins transiently up-regulated during vessel
      morphogenesis were screened for their potential as targets in antiangiogenic
      tumor therapy. The molecular chaperone alphaB-crystallin was identified as
      specifically induced with regard to expression level, modification by serine
      phosphorylation, and subcellular localization during tubular morphogenesis of
      endothelial cells. Small interfering RNA-mediated knockdown of alphaB-crystallin
      expression did not affect endothelial proliferation but led to attenuated tubular
      morphogenesis, early activation of proapoptotic caspase-3, and increased
      apoptosis. alphaB-crystallin was expressed in a subset of human tumor vessels but
      not in normal capillaries. Tumors grown in alphaB-crystallin(-/-) mice were
      significantly less vascularized than wild-type tumors and displayed increased
      areas of apoptosis/necrosis. Importantly, tumor vessels in alphaB-crystallin(-/-)
      mice were leaky and showed signs of caspase-3 activation and extensive apoptosis.
      Ultrastructural analyses showed defective vessels partially devoid of endothelial
      lining. These data strongly implicate alphaB-crystallin as an important regulator
      of tubular morphogenesis and survival of endothelial cell during tumor
      angiogenesis. Hereby we identify the small heat shock protein family as a novel
      class of angiogenic modulators.

PMID- 18063750
TI  - Escape from suppression: tumor-specific effector cells outcompete regulatory T
      cells following stem-cell transplantation.
AB  - Immune reconstitution of autologous hematopoietic stem-cell transplant recipients
      with the progeny of mature T cells in the graft leads to profound changes in the
      emerging functional T-cell repertoire. In the steady state, the host is
      frequently tolerant to tumor antigens, reflecting dominant suppression of naive
      and effector T cells by regulatory T cells (T(regs)). We examined the relative
      frequency and function of these 3 components within the tumor-specific T-cell
      compartment during immune reconstitution. Grafts from tumor-bearing donors
      exerted a significant antitumor effect in irradiated, syngeneic tumor-bearing
      recipients. This was associated with dramatic clonal expansion and interferon
      gamma (IFNgamma) production by previously tolerant tumor-specific T cells. While
      donor-derived T(regs) expanded in recipients, they did not inhibit the antigen
      driven expansion of effector T cells in the early posttransplantation period.
      Indeed, the repopulation of tumor-specific effector T cells significantly
      exceeded that of T(regs), the expansion of which was limited by IL-2
      availability. Although the intrinsic suppressive capacity of T(regs) remained
      intact, their diminished frequency was insufficient to suppress effector cell
      function. These findings provide an explanation for the reversal of tolerance
      leading to tumor rejection in transplant recipients and likely contribute to the
      efficacy of adoptive T-cell therapies in lymphopenic hosts.

PMID- 18063751
TI  - X-ray crystal structure of the fibrinolysis inhibitor alpha2-antiplasmin.
AB  - The serpin alpha(2)-antiplasmin (SERPINF2) is the principal inhibitor of plasmin
      and inhibits fibrinolysis. Accordingly, alpha(2)-antiplasmin deficiency in humans
      results in uncontrolled fibrinolysis and a bleeding disorder. alpha(2)
      antiplasmin is an unusual serpin, in that it contains extensive N- and C-terminal
      sequences flanking the serpin domain. The N-terminal sequence is crosslinked to
      fibrin by factor XIIIa, whereas the C-terminal region mediates the initial
      interaction with plasmin. To understand how this may happen, we have determined
      the 2.65A X-ray crystal structure of an N-terminal truncated murine alpha(2)
      antiplasmin. The structure reveals that part of the C-terminal sequence is
      tightly associated with the body of the serpin. This would be anticipated to
      position the flexible plasmin-binding portion of the C-terminus in close
      proximity to the serpin Reactive Center Loop where it may act as a template to
      accelerate serpin/protease interactions.

PMID- 18063752
TI  - Disease-associated CIAS1 mutations induce monocyte death, revealing low-level
      mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients.
AB  - Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic
      autoinflammatory disorders in which the majority of patients have mutations in
      the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having
      indistinguishable clinical features, some patients lack CIAS1 mutations by
      conventional nucleotide sequencing. We recently reported a CAPS patient with
      mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were
      overlooked in "mutation-negative" patients, due to a low frequency of mosaicism.
      To determine whether there were latent mutant cells in "mutation-negative"
      patients, we sought to identify mutation-associated biologic phenotypes of
      patients' monocytes. We found that lipopolysaccharide selectively induced
      necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death
      correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was
      independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes,
      was not mediated by the inflammatory milieu, and was independent of disease
      severity or anti-IL-1 therapy. By collecting dying monocytes after
      lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes
      and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS
      patients. Our findings reveal a novel effect of CIAS1 mutations in promoting
      necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important
      role in mutation-negative CAPS patients.

PMID- 18063753
TI  - Hls5 regulated erythroid differentiation by modulating GATA-1 activity.
AB  - Hemopoietic lineage switch (Hls) 5 and 7 were originally isolated as genes up
      regulated during an erythroid-to-myeloid lineage switch. We have shown previously
      that Hls7/Mlf1 imposes a monoblastoid phenotype on erythroleukemic cells. Here we
      show that Hls5 impedes erythroid maturation by restricting proliferation and
      inhibiting hemoglobin synthesis; however, Hls5 does not influence the morphology
      of erythroid cells. Under the influence of GATA-1, Hls5 relocates from
      cytoplasmic granules to the nucleus where it associates with both FOG-1 and GATA
      1. In the nucleus, Hls5 is able to suppress GATA-1-mediated transactivation and
      reduce GATA-1 binding to DNA. We conclude that Hls5 and Hls7/Mlf1 act
      cooperatively to induce biochemical and phenotypic changes associated with
      erythroid/myeloid lineage switching.

PMID- 18063754
TI  - Differential context-dependent effects of friend of GATA-1 (FOG-1) on mast-cell
      development and differentiation.
AB  - Friend of GATA-1 (FOG-1) is a binding partner of GATA-1, a zinc finger
      transcription factor with crucial roles in erythroid, megakaryocytic, and mast
      cell differentiation. FOG-1 is indispensable for the function of GATA-1 during
      erythro/megakaryopoiesis, but FOG-1 is not expressed in mast cells. Here, we
      analyzed the role of FOG-1 in mast-cell differentiation using a combined
      experimental system with conditional gene expression and in vitro hematopoietic
      induction of mouse embryonic stem cells. Expression of FOG-1 during the
      progenitor period inhibited the differentiation of mast cells and enhanced the
      differentiation of neutrophils. Analysis using a mutant of PU.1, a transcription
      factor that positively or negatively cooperates with GATA-1, revealed that this
      lineage skewing was caused by disrupted binding between GATA-1 and PU.1, which is
      a prerequisite for mast-cell differentiation. However, FOG-1 expression in mature
      mast cells brought approximately a reversible loss of the mast-cell phenotype. In
      contrast to the lineage skewing, the loss of the mast-cell phenotype was caused
      by down-regulation of MITF, a basic helix-loop-helix transcription factor
      required for mast-cell differentiation and maturation. These results indicate
      that FOG-1 inhibits mast-cell differentiation in a differentiation stage
      dependent manner, and its effects are produced via different molecular
      mechanisms.

PMID- 18063755
TI  - Smed-betacatenin-1 is required for anteroposterior blastema polarity in planarian
      regeneration.
AB  - Planarian flatworms can regenerate heads at anterior-facing wounds and tails at
      posterior-facing wounds throughout the body. How this regeneration polarity is
      specified has been a classic problem for more than a century. We identified a
      planarian gene, Smed-betacatenin-1, that controls regeneration polarity.
      Posterior-facing blastemas regenerate a head instead of a tail in Smed
      betacatenin-1(RNAi) animals. Smed-betacatenin-1 is required after wounding and at
      any posterior-facing wound for polarity. Additionally, intact Smed-betacatenin
      1(RNAi) animals display anteriorization during tissue turnover. Five Wnt genes
      and a secreted Frizzled-related Wnt antagonist-like gene are expressed in domains
      along the anteroposterior axis that reset to new positions during regeneration,
      which suggests that Wnts control polarity through Smed-betacatenin-1. Our data
      suggest that beta-catenin specifies the posterior character of the
      anteroposterior axis throughout the Bilateria and specifies regeneration polarity
      in planarians.

PMID- 18063756
TI  - Treatment of sickle cell anemia mouse model with iPS cells generated from
      autologous skin.
AB  - It has recently been demonstrated that mouse and human fibroblasts can be
      reprogrammed into an embryonic stem cell-like state by introducing combinations
      of four transcription factors. However, the therapeutic potential of such induced
      pluripotent stem (iPS) cells remained undefined. By using a humanized sickle cell
      anemia mouse model, we show that mice can be rescued after transplantation with
      hematopoietic progenitors obtained in vitro from autologous iPS cells. This was
      achieved after correction of the human sickle hemoglobin allele by gene-specific
      targeting. Our results provide proof of principle for using transcription factor
      induced reprogramming combined with gene and cell therapy for disease treatment
      in mice. The problems associated with using retroviruses and oncogenes for
      reprogramming need to be resolved before iPS cells can be considered for human
      therapy.

PMID- 18063758
TI  - Reduced North Atlantic deep water coeval with the glacial Lake Agassiz freshwater
      outburst.
AB  - An outstanding climate anomaly 8200 years before the present (B.P.) in the North
      Atlantic is commonly postulated to be the result of weakened overturning
      circulation triggered by a freshwater outburst. New stable isotopic and
      sedimentological records from a northwest Atlantic sediment core reveal that the
      most prominent Holocene anomaly in bottom-water chemistry and flow speed in the
      deep limb of the Atlantic overturning circulation begins at approximately 8.38
      thousand years B.P., coeval with the catastrophic drainage of Lake Agassiz. The
      influence of Lower North Atlantic Deep Water was strongly reduced at our site for
      approximately 100 years after the outburst, confirming the ocean's sensitivity to
      freshwater forcing. The similarities between the timing and duration of the
      pronounced deep circulation changes and regional climate anomalies support a
      causal link.

PMID- 18063759
TI  - Chinese science on the move.

PMID- 18063760
TI  - Mathematics education. U.S. expert panel sees algebra as key to improvements in
      math.

PMID- 18063757
TI  - Beta-catenin defines head versus tail identity during planarian regeneration and
      homeostasis.
AB  - After amputation, freshwater planarians properly regenerate a head or tail from
      the resulting anterior or posterior wound. The mechanisms that differentiate
      anterior from posterior and direct the replacement of the appropriate missing
      body parts are unknown. We found that in the planarian Schmidtea mediterranea,
      RNA interference (RNAi) of beta-catenin or dishevelled causes the inappropriate
      regeneration of a head instead of a tail at posterior amputations. Conversely,
      RNAi of the beta-catenin antagonist adenomatous polyposis coli results in the
      regeneration of a tail at anterior wounds. In addition, the silencing of beta
      catenin is sufficient to transform the tail of uncut adult animals into a head.
      We suggest that beta-catenin functions as a molecular switch to specify and
      maintain anteroposterior identity during regeneration and homeostasis in
      planarians.

PMID- 18063761
TI  - Clinical trials. Gene transfer an unlikely contributor to patient's death.

PMID- 18063762
TI  - Academic freedom. Thai science agency clamps down on sensitive research.

PMID- 18063763
TI  - Bioterrorism. Panel provides peer review of intelligence research.

PMID- 18063764
TI  - Neuroscience. Gene variant may influence how people learn from their mistakes.

PMID- 18063765
TI  - Archaeology. The vanishing Fremont.

PMID- 18063766
TI  - Malaria. Did they really say ... eradication?

PMID- 18063767
TI  - Paleontology. Paleontologists get x-ray vision.

PMID- 18063768
TI  - Paleontology. Dental evidence suggests Neandertals matured faster than we do.

PMID- 18063769
TI  - Virtual worlds, real healing.

PMID- 18063770
TI  - The age-old question of researcher innovation.

PMID- 18063771
TI  - Misreading Dr. Venter's genome.

PMID- 18063772
TI  - Comment on "Synthesis of ultra-incompressible superhard rhenium diboride at
      ambient pressure".
AB  - Chung et al. (Reports, 20 April 2007, p. 436) reported the synthesis of superhard
      rhenium diboride (ReB2) at ambient pressure. We show that ReB2, first synthesized
      at ambient pressure 45 years ago, is not a superhard material. Together with the
      high cost of Re, this makes the prospect for large-scale industrial applications
      of ReB2 doubtful.

PMID- 18063773
TI  - Ecology. China's forestry reforms.

PMID- 18063774
TI  - Biochemistry. How some pili pull.

PMID- 18063775
TI  - Physics. A whiff of chemistry in heavy electron physics.

PMID- 18063776
TI  - Astronomy. A texture in the sky?

PMID- 18063777
TI  - Ecology. How do roots interact?

PMID- 18063778
TI  - Retrospective: Arthur Kornberg (1918-2007).

PMID- 18063779
TI  - GE Prize-winning essay. Why Old World monkeys are resistant to HIV-1.

PMID- 18063780
TI  - GE Prize-winning essay. 2007 Grand prize winner.

PMID- 18063782
TI  - Sunrise. Introduction. Hinode.

PMID- 18063781
TI  - Optical quantum computing.
AB  - In 2001, all-optical quantum computing became feasible with the discovery that
      scalable quantum computing is possible using only single-photon sources, linear
      optical elements, and single-photon detectors. Although it was in principle
      scalable, the massive resource overhead made the scheme practically daunting.
      However, several simplifications were followed by proof-of-principle
      demonstrations, and recent approaches based on cluster states or error encoding
      have dramatically reduced this worrying resource overhead, making an all-optical
      architecture a serious contender for the ultimate goal of a large-scale quantum
      computer. Key challenges will be the realization of high-efficiency sources of
      indistinguishable single photons, low-loss, scalable optical circuits, high
      efficiency single-photon detectors, and low-loss interfacing of these components.

PMID- 18063783
TI  - Are there Alfven waves in the solar atmosphere?
AB  - The Sun's outer coronal layer exists at a temperature of millions of kelvins,
      much hotter than the solar surface we observe. How this high temperature is
      maintained and what energy sources are involved continue to puzzle and fascinate
      solar researchers. Recently, the Hinode spacecraft was launched to observe and
      measure the plasma properties of the Sun's outer layers. The data collected by
      Hinode reveal much about the role of magnetic field interactions and how plasma
      waves might transport energy to the corona. These results open a new era in high
      resolution observation of the Sun.

PMID- 18063784
TI  - Chromospheric alfvenic waves strong enough to power the solar wind.
AB  - Alfven waves have been invoked as a possible mechanism for the heating of the
      Sun's outer atmosphere, or corona, to millions of degrees and for the
      acceleration of the solar wind to hundreds of kilometers per second. However,
      Alfven waves of sufficient strength have not been unambiguously observed in the
      solar atmosphere. We used images of high temporal and spatial resolution obtained
      with the Solar Optical Telescope onboard the Japanese Hinode satellite to reveal
      that the chromosphere, the region sandwiched between the solar surface and the
      corona, is permeated by Alfven waves with strong amplitudes on the order of 10 to
      25 kilometers per second and periods of 100 to 500 seconds. Estimates of the
      energy flux carried by these waves and comparisons with advanced radiative
      magnetohydrodynamic simulations indicate that such Alfven waves are energetic
      enough to accelerate the solar wind and possibly to heat the quiet corona.

PMID- 18063785
TI  - Coronal transverse magnetohydrodynamic waves in a solar prominence.
AB  - Solar prominences are cool 10(4) kelvin plasma clouds supported in the
      surrounding 10(6) kelvin coronal plasma by as-yet-undetermined mechanisms.
      Observations from Hinode show fine-scale threadlike structures oscillating in the
      plane of the sky with periods of several minutes. We suggest that these represent
      Alfven waves propagating on coronal magnetic field lines and that these may play
      a role in heating the corona.

PMID- 18063786
TI  - Evidence for Alfven waves in solar x-ray jets.
AB  - Coronal magnetic fields are dynamic, and field lines may misalign, reassemble,
      and release energy by means of magnetic reconnection. Giant releases may generate
      solar flares and coronal mass ejections and, on a smaller scale, produce x-ray
      jets. Hinode observations of polar coronal holes reveal that x-ray jets have two
      distinct velocities: one near the Alfven speed ( approximately 800 kilometers per
      second) and another near the sound speed (200 kilometers per second). Many more
      jets were seen than have been reported previously; we detected an average of 10
      events per hour up to these speeds, whereas previous observations documented only
      a handful per day with lower average speeds of 200 kilometers per second. The x
      ray jets are about 2 x 10(3) to 2 x 10(4) kilometers wide and 1 x 10(5)
      kilometers long and last from 100 to 2500 seconds. The large number of events,
      coupled with the high velocities of the apparent outflows, indicates that the
      jets may contribute to the high-speed solar wind.

PMID- 18063787
TI  - Fine thermal structure of a coronal active region.
AB  - The determination of the fine thermal structure of the solar corona is
      fundamental to constraining the coronal heating mechanisms. The Hinode X-ray
      Telescope collected images of the solar corona in different passbands, thus
      providing temperature diagnostics through energy ratios. By combining different
      filters to optimize the signal-to-noise ratio, we observed a coronal active
      region in five filters, revealing a highly thermally structured corona: very fine
      structures in the core of the region and on a larger scale further away. We
      observed continuous thermal distribution along the coronal loops, as well as
      entangled structures, and variations of thermal structuring along the line of
      sight.

PMID- 18063788
TI  - Continuous plasma outflows from the edge of a solar active region as a possible
      source of solar wind.
AB  - The Sun continuously expels a huge amount of ionized material into interplanetary
      space as the solar wind. Despite its influence on the heliospheric environment,
      the origin of the solar wind has yet to be well identified. In this paper, we
      report Hinode X-ray Telescope observations of a solar active region. At the edge
      of the active region, located adjacent to a coronal hole, a pattern of continuous
      outflow of soft-x-ray-emitting plasmas was identified emanating along apparently
      open magnetic field lines and into the upper corona. Estimates of temperature and
      density for the outflowing plasmas suggest a mass loss rate that amounts to
      approximately 1/4 of the total mass loss rate of the solar wind. These outflows
      may be indicative of one of the solar wind sources at the Sun.

PMID- 18063789
TI  - Slipping magnetic reconnection in coronal loops.
AB  - Magnetic reconnection of solar coronal loops is the main process that causes
      solar flares and possibly coronal heating. In the standard model, magnetic field
      lines break and reconnect instantaneously at places where the field mapping is
      discontinuous. However, another mode may operate where the magnetic field mapping
      is continuous but shows steep gradients: The field lines may slip across each
      other. Soft x-ray observations of fast bidirectional motions of coronal loops,
      observed by the Hinode spacecraft, support the existence of this slipping
      magnetic reconnection regime in the Sun's corona. This basic process should be
      considered when interpreting reconnection, both on the Sun and in laboratory
      based plasma experiments.

PMID- 18063790
TI  - Chromospheric anemone jets as evidence of ubiquitous reconnection.
AB  - The heating of the solar chromosphere and corona is a long-standing puzzle in
      solar physics. Hinode observations show the ubiquitous presence of chromospheric
      anemone jets outside sunspots in active regions. They are typically 3 to 7 arc
      seconds = 2000 to 5000 kilometers long and 0.2 to 0.4 arc second = 150 to 300
      kilometers wide, and their velocity is 10 to 20 kilometers per second. These
      small jets have an inverted Y-shape, similar to the shape of x-ray anemone jets
      in the corona. These features imply that magnetic reconnection similar to that in
      the corona is occurring at a much smaller spatial scale throughout the
      chromosphere and suggest that the heating of the solar chromosphere and corona
      may be related to small-scale ubiquitous reconnection.

PMID- 18063791
TI  - Small-scale jetlike features in penumbral chromospheres.
AB  - We observed fine-scale jetlike features, referred to as penumbral microjets, in
      chromospheres of sunspot penumbrae. The microjets were identified in image
      sequences of a sunspot taken through a Ca II H-line filter on the Solar Optical
      Telescope on board the Japanese solar physics satellite Hinode. The microjets'
      small width of 400 kilometers and short duration of less than 1 minute make them
      difficult to identify in existing observations. The microjets are possibly caused
      by magnetic reconnection in the complex magnetic configuration in penumbrae and
      have the potential to heat the corona above a sunspot.

PMID- 18063792
TI  - Twisting motions of sunspot penumbral filaments.
AB  - The penumbra of a sunspot is composed of numerous thin, radially extended, bright
      and dark filaments carrying outward gas flows (the Evershed flow). Using high
      resolution images obtained by the Solar Optical Telescope aboard the solar
      physics satellite Hinode, we discovered a number of penumbral bright filaments
      revealing twisting motions about their axes. These twisting motions are observed
      only in penumbrae located in the direction perpendicular to the symmetry line
      connecting the sunspot center and the solar disk center, and the direction of the
      twist (that is, lateral motions of intensity fluctuation across filaments) is
      always from limb side to disk-center side. Thus, the twisting feature is not an
      actual twist or turn of filaments but a manifestation of dynamics of penumbral
      filaments with three-dimensional radiative transfer effects.

PMID- 18063793
TI  - Economics of overexploitation revisited.
AB  - About 25% of the world's fisheries are depleted such that their current biomass
      is lower than the level that would maximize the sustained yield (MSY). By using
      methods not previously applied in the fisheries conservation context, we show in
      four disparate fisheries (including the long-lived and slow-growing orange
      roughy) that the dynamic maximum economic yield (MEY), the biomass that produces
      the largest discounted economic profits from fishing, exceeds MSY. Thus, although
      it is theoretically possible that maximizing discounted economic profits may
      cause stock depletions, our results show there is a win-win: In many fisheries at
      reasonable discount rates and at current prices and costs, larger fish stocks
      increase economic profits. An MEY target that exceeds MSY and transfers from
      higher, future profits to compensate fishers for the transition costs of stock
      rebuilding would help overcome a key cause of fisheries overexploitation,
      industry opposition to lower harvests.

PMID- 18063794
TI  - Saturn's small inner satellites: clues to their origins.
AB  - Cassini images of Saturn's small inner satellites (radii of less than
      approximately 100 kilometers) have yielded their sizes, shapes, and in some
      cases, topographies and mean densities. This information and numerical N-body
      simulations of accretionary growth have provided clues to their internal
      structures and origins. The innermost ring-region satellites have likely grown to
      the maximum sizes possible by accreting material around a dense core about one
      third to one-half the present size of the moon. The other small satellites
      outside the ring region either may be close to monolithic collisional shards,
      modified to varying degrees by accretion, or may have grown by accretion without
      the aid of a core. We derived viscosity values of 87 and 20 square centimeters
      per second, respectively, for the ring material surrounding ring-embedded Pan and
      Daphnis. These moons almost certainly opened their respective gaps and then grew
      to their present size early on, when the local ring environment was thicker than
      it is today.

PMID- 18063795
TI  - Structure of a site-2 protease family intramembrane metalloprotease.
AB  - Regulated intramembrane proteolysis by members of the site-2 protease (S2P)
      family is an important signaling mechanism conserved from bacteria to humans.
      Here we report the crystal structure of the transmembrane core domain of an S2P
      metalloprotease from Methanocaldococcus jannaschii. The protease consists of six
      transmembrane segments, with the catalytic zinc atom coordinated by two histidine
      residues and one aspartate residue approximately 14 angstroms into the lipid
      membrane surface. The protease exhibits two distinct conformations in the
      crystals. In the closed conformation, the active site is surrounded by
      transmembrane helices and is impermeable to substrate peptide; water molecules
      gain access to zinc through a polar, central channel that opens to the cytosolic
      side. In the open conformation, transmembrane helices alpha1 and alpha6 separate
      from each other by 10 to 12 angstroms, exposing the active site to substrate
      entry. The structure reveals how zinc embedded in an integral membrane protein
      can catalyze peptide cleavage.

PMID- 18063796
TI  - Designing superoleophobic surfaces.
AB  - Understanding the complementary roles of surface energy and roughness on natural
      nonwetting surfaces has led to the development of a number of biomimetic
      superhydrophobic surfaces, which exhibit apparent contact angles with water
      greater than 150 degrees and low contact angle hysteresis. However,
      superoleophobic surfaces-those that display contact angles greater than 150
      degrees with organic liquids having appreciably lower surface tensions than that
      of water-are extremely rare. Calculations suggest that creating such a surface
      would require a surface energy lower than that of any known material. We show how
      a third factor, re-entrant surface curvature, in conjunction with chemical
      composition and roughened texture, can be used to design surfaces that display
      extreme resistance to wetting from a number of liquids with low surface tension,
      including alkanes such as decane and octane.

PMID- 18063797
TI  - The equatorial ridges of Pan and Atlas: terminal accretionary ornaments?
AB  - In the outer regions of Saturn's main rings, strong tidal forces balance
      gravitational accretion processes. Thus, unusual phenomena may be expected there.
      The Cassini spacecraft has recently revealed the strange "flying saucer" shape of
      two small satellites, Pan and Atlas, located in this region, showing prominent
      equatorial ridges. The accretion of ring particles onto the equatorial surfaces
      of already-formed bodies embedded in the rings may explain the formation of the
      ridges. This ridge formation process is in good agreement with detailed Cassini
      images showing differences between rough polar and smooth equatorial terrains. We
      propose that Pan and Atlas ridges are kilometers-thick "ring-particle piles"
      formed after the satellites themselves and after the flattening of the rings but
      before the complete depletion of ring material from their surroundings.

PMID- 18063798
TI  - Stabilizing isopeptide bonds revealed in gram-positive bacterial pilus structure.
AB  - Many bacterial pathogens have long, slender pili through which they adhere to
      host cells. The crystal structure of the major pilin subunit from the Gram
      positive human pathogen Streptococcus pyogenes at 2.2 angstroms resolution
      reveals an extended structure comprising two all-beta domains. The molecules
      associate in columns through the crystal, with each carboxyl terminus adjacent to
      a conserved lysine of the next molecule. This lysine forms the isopeptide bonds
      that link the subunits in native pili, validating the relevance of the crystal
      assembly. Each subunit contains two lysine-asparagine isopeptide bonds generated
      by an intramolecular reaction, and we find evidence for similar isopeptide bonds
      in other cell surface proteins of Gram-positive bacteria. The present structure
      explains the strength and stability of such Gram-positive pili and could
      facilitate vaccine development.

PMID- 18063799
TI  - Sensing X chromosome pairs before X inactivation via a novel X-pairing region of
      the Xic.
AB  - Mammalian dosage compensation involves silencing of one of the two X chromosomes
      in females and is controlled by the X-inactivation center (Xic). The Xic, which
      includes Xist and its antisense transcription unit Tsix/Xite, somehow senses the
      number of X chromosomes and triggers Xist up-regulation from one of the two X
      chromosomes in females. We found that a segment of the mouse Xic lying several
      hundred kilobases upstream of Xist brings the two Xics together before the onset
      of X inactivation. This region can autonomously drive Xic trans-interactions even
      as an ectopic single-copy transgene. Its introduction into male embryonic stem
      cells is strongly selected against, consistent with a possible role in trans
      activating Xist. We propose that homologous associations driven by this novel X
      pairing region (Xpr) of the Xic enable a cell to sense that more than one X
      chromosome is present and coordinate reciprocal Xist/Tsix expression.

PMID- 18063800
TI  - Genetically determined differences in learning from errors.
AB  - The role of dopamine in monitoring negative action outcomes and feedback-based
      learning was tested in a neuroimaging study in humans grouped according to the
      dopamine D2 receptor gene polymorphism DRD2-TAQ-IA. In a probabilistic learning
      task, A1-allele carriers with reduced dopamine D2 receptor densities learned to
      avoid actions with negative consequences less efficiently. Their posterior medial
      frontal cortex (pMFC), involved in feedback monitoring, responded less to
      negative feedback than others' did. Dynamically changing interactions between
      pMFC and hippocampus found to underlie feedback-based learning were reduced in A1
      allele carriers. This demonstrates that learning from errors requires
      dopaminergic signaling. Dopamine D2 receptor reduction seems to decrease
      sensitivity to negative action consequences, which may explain an increased risk
      of developing addictive behaviors in A1-allele carriers.

PMID- 18063801
TI  - Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by
      NADPH-oxidase.
AB  - Abuse of the dissociative anesthetic ketamine can lead to a syndrome
      indistinguishable from schizophrenia. In animals, repetitive exposure to this N
      methyl-d-aspartate-receptor antagonist induces the dysfunction of a subset of
      cortical fast-spiking inhibitory interneurons, with loss of expression of
      parvalbumin and the gamma-aminobutyric acid-producing enzyme GAD67. We show here
      that exposure of mice to ketamine induced a persistent increase in brain
      superoxide due to activation in neurons of reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase. Decreasing superoxide production
      prevented the effects of ketamine on inhibitory interneurons in the prefrontal
      cortex. These results suggest that NADPH oxidase may represent a novel target for
      the treatment of ketamine-induced psychosis.

PMID- 18063802
TI  - Rare AU-1-like G3P[9] human rotaviruses with a Kun-like NSP4 gene detected in
      children with diarrhea in Italy.
AB  - Three G3P[9] rotaviruses, detected in children hospitalized with gastroenteritis
      in Palermo, Italy, were found to be genetically related to strains of either
      human or feline origin in the VP7, VP4, and VP6 genes. In contrast, in the NSP4
      gene the viruses resembled G2P[4] human strains, suggesting a reassortment
      between AU-1-like and Kun-like strains.

PMID- 18063804
TI  - Role played by P2X and P2Y receptors in evoking the muscle chemoreflex.
AB  - The role played by purinergic 2Y receptors in evoking the muscle chemoreflex is
      not well defined. To shed light on this issue, we compared the pressor responses
      with popliteal arterial injection of UTP (1 mg/kg), a selective P2Y agonist, with
      those to popliteal arterial injection of ATP (1 mg/kg), a P2X and P2Y agonist,
      and to alpha,beta-methylene ATP (50 mug/kg), a selective P2X1 and P2X3 agonist,
      in decerebrate unanesthetized cats. We found that injection of ATP and alpha,beta
      methylene ATP increased mean arterial pressure by 19 +/- 2 and 15 +/- 4 mmHg,
      whereas UTP had no affect on arterial pressure. In addition, the pressor
      responses to injection of ATP and alpha,beta-methylene ATP were abolished by
      section of the sciatic nerve, demonstrating that they were reflex in origin. We
      conclude that P2Y receptors on thin fiber muscle afferents play no role in
      evoking the muscle chemoreflex.

PMID- 18063803
TI  - Importance of hemodynamic forces as signals for exercise-induced changes in
      endothelial cell phenotype.
AB  - Current evidence indicates that the ability of physical activity to sustain a
      normal phenotype of arterial endothelial cells (ECs) plays a central role in the
      beneficial effects of exercise (Ex) on atherosclerotic disease. Here we evaluate
      the strength of evidence that shear stress (SS) and/or circumferential wall
      stress (stretch) are the primary signals, produced by bouts of Ex, that signal
      altered gene expression in arterial ECs, thereby resulting in a less atherogenic
      EC phenotype. Current literature indicates that SS is a signal for expression of
      antiatherogenic genes in cultured ECs, in ECs of isolated arteries, and in ECs of
      arteries in intact animals. Furthermore, SS levels in the arteries of humans
      during Ex are in the range that produces beneficial changes. In contrast, complex
      flow profiles within recirculation zones and/or oscillatory flow patterns can
      cause proatherogenic gene expression in ECs. In vivo evidence indicates that Ex
      decreases oscillatory flow/SS in some portions of the arterial tree but may
      increase oscillatory flow in other areas of the arterial tree. Circumferential
      wall stress can increase expression of some beneficial EC genes as well, but
      circumferential wall stress also increases production of reactive oxygen species
      and increases the expression of adhesion factors and other proatherogenic genes.
      Interactions of arterial pressure and fluid SS play an important role in arterial
      vascular health and likely contribute to how Ex bouts signal changes in EC gene
      expression. It is also clear that other local and circulating factors interact
      with these hemodynamic signals during Ex to produce the healthy arterial EC
      phenotype. We conclude that available evidence suggests that exercise signals
      formation of beneficial endothelial cell phenotype at least in part through
      changes in SS and wall stretch in the arteries.

PMID- 18063805
TI  - AMP-activated protein kinase phosphorylates transcription factors of the CREB
      family.
AB  - AMP-activated protein kinase (AMPK) has been identified as a regulator of gene
      transcription, increasing mitochondrial proteins of oxidative metabolism as well
      as hexokinase expression in skeletal muscle. In mice, muscle-specific knockout of
      LKB1, a component of the upstream kinase of AMPK, prevents contraction- and 5
      aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR)-induced activation
      of AMPK in skeletal muscle, and the increase in hexokinase II protein that is
      normally observed with chronic AICAR activation of AMPK. Since previous reports
      show a cAMP response element in the promoter region of the hexokinase II gene, we
      hypothesized that the cAMP-response element (CRE) binding protein (CREB) family
      of transcription factors could be targets of AMPK. Using radioisotopic kinase
      assays, we found that recombinant and rat liver and muscle AMPK phosphorylated
      CREB1 at the same site as cAMP-dependent protein kinase (PKA). AMPK was also
      found to phosphorylate activating transcription factor 1 (ATF1), CRE modulator
      (CREM), and CREB-like 2 (CREBL2), but not ATF2. Treatment of HEK-293 cells stably
      transfected with a CREB-driven luciferase reporter with AICAR increased
      luciferase activity approximately threefold over a 24-h time course. This
      increase was blocked with compound C, an AMPK inhibitor. In addition, AICAR
      induced activation of AMPK in incubated rat epitrochlearis muscles resulted in an
      increase in both phospho-acetyl-CoA carboxylase and phospho-CREB. We conclude
      that CREB and related proteins are direct downstream targets for AMPK and are
      therefore likely involved in mediating some effects of AMPK on expression of
      genes having a CRE in their promoters.

PMID- 18063806
TI  - Early changes of lung function and structure in an elastase model of emphysema--a
      hyperpolarized 3He MRI study.
AB  - Early changes of lung function and structure were studied in the presence of an
      elastase-induced model of emphysema in 35 Sprague-Dawley rats at mild (5 U/100 g)
      and moderate (10 U/100 g) severities. Lung ventilation was measured on a regional
      basis (at a planar resolution of 3.2 mm) by hyperpolarized 3He MRI at 5 and 10 wk
      after model induction. Subsequent to imaging, average alveolar diameter was
      measured from histological slices taken from the centers of each lobe. Changes of
      mean fractional ventilation, mean linear intercept, and intrasubject
      heterogeneity of ventilation were studied during disease progression. Mean
      fractional ventilation was significantly different between healthy controls (0.23
      +/- 0.04) and emphysematous animals at both time points in the 10-unit group
      (0.06 +/- 0.02 and 0.12 +/- 0.05, respectively). Changes in average alveolar
      diameter were not statistically observable until the 10th wk between healthy (37
      +/- 10 microm) and emphysematous rats (73 +/- 25 and 95 +/- 31 microm, for 5 and
      10 units, respectively). Assessment of function-structure correlation suggested
      that the majority of the decline in fractional ventilation occurred in the first
      5 wk, while enlargement of alveolar diameters appeared primarily between the 5th
      and 10th wk. A thresholding metric, based on the 20th percentile of fractional
      ventilation over the entire lung, was utilized to detect the onset of the disease
      with confidence, independent of whether the regional ventilation measurements
      were normalized with respect to the delivered tidal volume and estimated
      functional residual capacity of each individual rat.

PMID- 18063807
TI  - Human ApoA-I transfer attenuates transplant arteriosclerosis via enhanced
      incorporation of bone marrow-derived endothelial progenitor cells.
AB  - OBJECTIVE: Transplant arteriosclerosis is the leading cause of graft failure and
      death in patients with heart transplantation. Endothelial progenitor cells (EPCs)
      contribute to endothelial regeneration in allografts. We investigated whether
      increased HDL cholesterol induced by adenoviral human apoA-I (AdA-I) transfer
      increases number and function of EPCs, promotes incorporation of EPCs in Balb/c
      allografts transplanted paratopically in C57BL/6 ApoE-/- mice, and attenuates
      transplant arteriosclerosis. METHODS AND RESULTS: EPC number in ApoE-/- mice was
      increased after AdA-I transfer as evidenced by 1.5-fold (P<0.01) higher Flk-1 Sca
      1-positive cells and 1.4-fold (P<0.01) higher DiI-acLDL isolectin-positive spleen
      cells. In addition, HDL enhanced EPC function in vitro. Incorporation of bone
      marrow-derived EPCs was 5.8-fold (P<0.01) higher at day 21 after transplantation
      in AdA-I-treated apoE-/- mice compared with control mice. Enhanced endothelial
      regeneration in AdA-I-treated apoE-/- mice as evidenced by a 2.6-fold (P<0.01)
      increase of CD31-positive endothelial cells resulted in a 1.4-fold (P=0.059)
      reduction of neointima and a 3.9-fold (P<0.01) increase of luminal area.
      CONCLUSIONS: Human apoA-I transfer increases the number of circulating EPCs,
      enhances their incorporation into allografts, promotes endothelial regeneration,
      and attenuates neointima formation in a murine model of transplant
      arteriosclerosis.

PMID- 18063808
TI  - Time since menopause influences the acute and chronic effect of estrogens on
      endothelial function.
AB  - OBJECTIVE: We evaluated whether time since menopause influences the acute and
      chronic effect of Estradiol (E) on vascular endothelial function. METHODS AND
      RESULTS: We studied flow-mediated dilatation (FMD) in 134 postmenopausal women
      (PMW) before and after acute and chronic E administration. At baseline FMD was
      inversely associated to time from menopause (r=-0.67, P<0.001) and age (r=-0.43,
      P<0.05), in exogenous estrogen naive but not in previous users. Acute and chronic
      E improved endothelial function in all women. E administration improved FMD more
      in women within 5 years since menopause than in those with more than 5 years
      since menopause (76% and 74% versus 45% and 48%, acute and chronic E,
      respectively; P<0.05). Among women with more than 5 years since menopause acute
      and chronic E increased FMD more in previous E users than in nonusers (59% and
      63% versus 31% and 38%, acute and chronic E, respectively; P<0.01). Multivariate
      analysis showed that time from menopause was a predictor of impaired FMD and of
      its improvement after acute and chronic E. CONCLUSIONS: Time from menopause
      influences FMD in PMW. The acute and chronic effect of E on FMD is time dependent
      and is reduced by a longer time since menopause.

PMID- 18063809
TI  - Molecular basis for Staphylococcus aureus-mediated platelet aggregate formation
      under arterial shear in vitro.
AB  - OBJECTIVE: Staphylococcus aureus is the most frequent causative organism of
      infective endocarditis (IE) and is characterized by thrombus formation on a
      cardiac valve that can embolize to a distant site. Previously, we showed that S.
      aureus clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) can
      stimulate rapid platelet aggregation. METHODS AND RESULTS: In this study we
      investigate their relative roles in mediating aggregate formation under
      physiological shear conditions. Platelets failed to interact with immobilized
      wild-type S. aureus (Newman) at shear rates <500 s(-1) but rapidly formed an
      aggregate at shear rates >800 s(-1). Inactivation of the ClfA gene eliminated
      aggregate formation at any shear rate. Using surrogate hosts that do not interact
      with platelets bacteria overexpressing ClfA supported rapid aggregate formation
      under high shear with a similar profile to Newman whereas bacteria overexpressing
      FnBPA did not. Fibrinogen binding to ClfA was found to be essential for aggregate
      formation although fibrinogen-coated surfaces only allowed single-platelets to
      adhere under all shear conditions. Blockade of the platelet immunoglobulin
      receptor Fc gammaRIIa inhibited aggregate formation. CONCLUSIONS: Thus,
      fibrinogen and IgG binding to ClfA is essential for aggregate formation under
      arterial shear conditions and may explain why S. aureus is the major cause of IE.

PMID- 18063810
TI  - Tea consumption is inversely associated with carotid plaques in women.
AB  - OBJECTIVE: The aim of this study was to assess the relationship of tea
      consumption with common carotid artery intima-media thickness (CCA-IMT) and
      carotid plaques. METHODS AND RESULTS: The study was performed on 6597 subjects
      aged > or = 65 years, recruited in the French population for the Three-City
      Study. Atherosclerotic plaques in the extracranial carotid arteries and CCA-IMT
      were measured using a standardized protocol. Results were tested for replication
      in another, younger, French population sample (EVA-Study, 1123 subjects). In the
      Three-City Study, increasing daily tea consumption was associated with a lower
      prevalence of carotid plaques in women: 44.0%, 42.5%, and 33.7% in women drinking
      no tea, 1 to 2 cups/d, and > or = 3 cups/d (P=0.0001). This association was
      independent of age, center, major vascular risk factors, educational level, and
      dietary habits (adjOR=0.68[95%CI:0.54 to 0.86] for women drinking > or = 3 cups/d
      compared with none). There was no association of tea consumption with carotid
      plaques in men, or CCA-IMT in both genders. In the EVA-Study, carotid plaque
      frequency was 18.8%, 18.5%, and 8.9% in women drinking no tea, 1 to 2 cups/d, and
      > or = 3 cups/d (P=0.08). CONCLUSIONS: In a large sample of elderly community
      subjects we showed for the first time that carotid plaques were less frequent
      with increasing tea consumption in women.

PMID- 18063811
TI  - Forkhead factor, FOXO3a, induces apoptosis of endothelial cells through
      activation of matrix metalloproteinases.
AB  - BACKGROUND: The forkhead factor, FOXO3a, is known to induce apoptosis in
      endothelial cells (ECs). However, its effects on extracellular matrices (ECM),
      which are important in EC survival, remained unknown. Here, we evaluated the role
      of FOXO3a on EC-ECM interaction. METHODS AND RESULTS: Constitutively active
      FOXO3a was transduced to human umbilical vein endothelial cells by adenoviral
      vector (Ad-TM-FOXO3a). Ad-TM-FOXO3a transfection led to dehiscence of ECs from
      fibronectin-coated plates, resulting in anoikis, which was significantly reversed
      by matrix metalloproteinase (MMP) inhibitor, GM6001. FOXO3a increased the
      expression of MMP-3 (stromelysin-1) but decreased the expression of tissue
      inhibitors of metalloproteinases-1 (TIMP-1), which was associated with increased
      MMP enzymatic activity in zymography. Pathophysiologic conditions such as serum
      starvation or heat shock also induced activation of endogenous FOXO3a, leading to
      activation of MMP-3 and apoptosis, which was reversed by GM6001. Delivery of Ad
      TM-FOXO3a to the intraluminal surface in vivo led to EC denudation, disrupted
      vascular integrity, and impaired endothelium-dependent vasorelaxation.
      CONCLUSIONS: Activation of MMPs and possible ECM disruption represent novel
      mechanisms of FOXO3a-mediated apoptosis in ECs.

PMID- 18063813
TI  - Biochemical importance of glycosylation in thrombin activatable fibrinolysis
      inhibitor.
AB  - Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa) exerts an
      antifibrinolytic effect by removing C-terminal lysines from partially degraded
      fibrin. These lysines are essential for a rapid conversion of plasminogen to
      plasmin by tissue type plasminogen activator. TAFI is heavily glycosylated at
      Asn22, Asn51, Asn63, and Asn86. Although the glycans occurring at the
      glycosylation sites have previously been identified, the biochemical role of
      these glycans is not known yet. Therefore, we have determined the biochemical
      importance of the glycosylation in TAFI. Four single, 6 double, 4 triple, and 1
      quadruple mutant, in which asparagine was replaced by glutamine, were constructed
      and transfected into HEK293T cells. Based on the determination of antigen and
      activity levels on conditioned medium, 4 single and 1 triple mutant were purified
      and their biochemical properties were determined. The glycosylation knockout
      mutants did neither reveal an altered fragmentation pattern nor differences in
      TAFIa stability, but TAFI-N51Q, TAFI-N63Q, and TAFI-N22Q-N51Q-N63Q revealed a
      decreased TAFIa activity, an increased intrinsic catalytic activity of the
      zymogen, and a decreased antifibrinolytic potential compared with TAFI-wild-type,
      whereas TAFI-N22Q and TAFI-N86Q revealed an increased antifibrinolytic potential
      probably because of an increased catalytic efficiency toward the physiological
      substrate. From these data it can be concluded that mainly the glycosylation at
      Asn86 contributes to the biochemical characteristics of TAFI. Furthermore we
      provide evidence that the activation peptide stays in close proximity to the
      TAFIa moiety after activation.

PMID- 18063812
TI  - Thromboxane receptor activates the AMP-activated protein kinase in vascular
      smooth muscle cells via hydrogen peroxide.
AB  - Thromboxane A2 receptor (TPr) stimulation induces cellular hypertrophy in
      vascular smooth muscle cells (VSMCs); however, regulation of VSMC hypertrophy
      remains poorly understood. Here we show that TPr stimulation activates AMP
      activated kinase (AMPK), which in turn limits TPr-induced protein synthesis in
      VSMCs. Exposure of cultured VSMCs to either TPr agonists, IBOP and U46619, or
      exogenous hydrogen peroxide (H2O2) caused time- and dose-dependent AMPK
      activation, as evidenced by increased phosphorylation of both AMPK-Thr172 and
      acetyl-coenzyme A carboxylase-Ser79, a downstream enzyme of AMPK, whereas
      SQ29548, a selective TPr antagonist, significantly attenuated TPr-enhanced AMPK
      activation. In parallel, both IBOP and U46619 significantly increased the
      production of reactive oxygen species such as H2O2. Furthermore, adenoviral
      overexpression of catalase (an H2O2 scavenger) abolished, whereas superoxide
      dismutase (which catalyzes H2O2 formation) enhanced, IBOP-induced AMPK
      activation, suggesting that TPr-activated AMPK was mediated by H2O2.
      Consistently, exposure of VSMCs to either TPr agonists or exogenous H2O2 dose
      dependently increased the phosphorylation of LKB1 (at serines 428 and 307), an
      AMPK kinase, as well as coimmunoprecipitation of AMPK with LKB1. In addition,
      direct mutagenesis of either Ser428 or Ser307 of LKB1 into alanine, like the
      kinase-dead LKB1 mutant, abolished both TPr-stimulated AMPK activation and
      coimmunoprecipitation. Finally, genetic inhibition of AMPK significantly
      accentuated IBOP-enhanced protein synthesis, whereas adenoviral overexpression of
      constitutively active AMPK abolished IBOP-enhance protein synthesis in VSMCs. We
      conclude that TPr stimulation triggers reactive oxygen species-mediated LKB1
      dependent AMPK activation, which in return inhibits cellular protein synthesis in
      VSMCs.

PMID- 18063814
TI  - Targeted rearrangement of floxed alleles in smooth muscle cells in vivo.

PMID- 18063815
TI  - The carboxy terminal domain of connexin43: from molecular regulation of the gap
      junction channel to supramolecular organization of the intercalated disk.

PMID- 18063816
TI  - Searching for causality of knocking out Txnip: is Txnip missing in action?

PMID- 18063817
TI  - Which connexins connect?

PMID- 18063818
TI  - Emerging role of microRNAs in cardiovascular biology.
AB  - The heart is among the most conserved organs of the body and is susceptible to
      defects more than any other organ. Heart malformations, in fact, occur in roughly
      1% of newborns. Moreover, cardiovascular disease arising during adult life is
      among the main causes of morbidity and mortality in developed countries. It is
      not surprising, therefore, that much effort is being channeled into understanding
      the development, physiology, and pathology of the cardiovascular system.
      MicroRNAs, a newly discovered class of small ribonucleotide-based regulators of
      gene expression, are being implicated in an increasing number of biological
      processes, and the study of their role in cardiovascular biology is just
      beginning. Here, we briefly overview microRNAs in general and report on the
      recent findings regarding their importance for the heart and vasculature, in
      particular. The new insights that are being gained will permit not only a greater
      understanding of cardiovascular pathologies but also, hopefully, the development
      of novel therapeutic strategies.

PMID- 18063819
TI  - Leptin and nitric oxide production against ischemic neuronal injury.

PMID- 18063820
TI  - Emboli formation rather than inflammatory mediators are responsible for increased
      cerebral water content after conventional and assisted beating-heart myocardial
      revascularization in a porcine model.
AB  - BACKGROUND AND PURPOSE: Emboli and proinflammatory mediators are suspected of
      generating cerebral edema after coronary surgery. In contrast to cardiopulmonary
      bypass (CPB), off-pump coronary artery bypass surgery (OPCAB) reduces microemboli
      count and proinflammatory mediator release but carries the risk of hemodynamic
      instability. A microaxial blood pump can augment cardiac output. METHODS:
      Coronary bypasses were constructed in pigs with CPB and cardioplegia (n=9), OPCAB
      (n=9), or blood-pump support CAB (n=9). Nine animals underwent sham operation.
      Embolus count was monitored and regional cerebral blood flow was assessed with
      microspheres in 21 brain specimens per animal (n=189 per group). Interleukins 6
      and 8 and tumor necrosis factor-alpha concentrations were determined. These
      variables were studied before, during, and for 4 hours after surgery. Finally,
      cerebral water content was determined. RESULTS: During CPB and blood-pump CAB, a
      significant number of emboli were counted in contrast to OPCAB and controls
      (P<0.05). During CPB, regional cerebral blood flow was affected (32 of 189) and
      showed reactive hyperemia except in 10 specimens after aortic cross-clamp
      release. This impairment persisted in 20 specimens. During and after OPCAB,
      regional cerebral blood flow remained nearly unchanged but showed low flow during
      (58 of 189) and after (35 of 189) the blood-pump run. A significant increase in
      proinflammatory mediators was observed only in the CPB group. CPB and blood-pump
      CAB significantly increased cerebral water content (P<0.05). A strong correlation
      between embolic load and cerebral water content was observed in all groups. No
      correlation between proinflammatory mediator release and cerebral water content
      was detected. CONCLUSIONS: Emboli formation rather than inflammatory mediators
      are responsible for increased cerebral water content after conventional and
      assisted beating-heart myocardial revascularization.

PMID- 18063822
TI  - Mortality associated with carotid endarterectomy for asymptomatic stenosis.

PMID- 18063821
TI  - Metabolic syndrome and ischemic stroke risk: Northern Manhattan Study.
AB  - BACKGROUND AND PURPOSE: More than 47 million individuals in the United States
      meet the criteria for the metabolic syndrome. The relation between the metabolic
      syndrome and stroke risk in multiethnic populations has not been well
      characterized. METHODS: As part of the Northern Manhattan Study, 3298 stroke-free
      community residents were prospectively followed up for a mean of 6.4 years. The
      metabolic syndrome was defined according to guidelines established by the
      National Cholesterol Education Program Adult Treatment Panel III. Cox
      proportional-hazards models were used to calculate hazard ratios (HRs) and 95%
      CIs for ischemic stroke and vascular events (ischemic stroke, myocardial
      infarction, or vascular death). The etiologic fraction estimates the proportion
      of events attributable to the metabolic syndrome. RESULTS: More than 44% of the
      cohort had the metabolic syndrome (48% of women vs 38% of men, P<0.0001), which
      was more prevalent among Hispanics (50%) than whites (39%) or blacks (37%). The
      metabolic syndrome was associated with increased risk of stroke (HR=1.5; 95% CI,
      1.1 to 2.2) and vascular events (HR=1.6; 95% CI, 1.3 to 2.0) after adjustment for
      sociodemographic and risk factors. The effect of the metabolic syndrome on stroke
      risk was greater among women (HR=2.0; 95% CI, 1.3 to 3.1) than men (HR=1.1; 95%
      CI, 0.6 to 1.9) and among Hispanics (HR=2.0; 95% CI, 1.2 to 3.4) compared with
      blacks and whites. The etiologic fraction estimates suggest that elimination of
      the metabolic syndrome would result in a 19% reduction in overall stroke, a 30%
      reduction of stroke in women; and a 35% reduction of stroke among Hispanics.
      CONCLUSIONS: The metabolic syndrome is an important risk factor for ischemic
      stroke, with differential effects by sex and race/ethnicity.

PMID- 18063823
TI  - Influence of inflammatory variables on intima-media thickness.

PMID- 18063824
TI  - Evidence of abnormal lower-limb torque coupling after stroke: an isometric study.
AB  - BACKGROUND AND PURPOSE: Although stroke survivors often display abnormal joint
      torque patterns, studies of torque-coupling in the lower limb are lacking,
      despite their potential impact on gait abnormalities. METHODS: Twenty-two chronic
      ambulating stroke subjects and 11 age-matched control subjects produced isometric
      hip torques in the frontal and sagittal planes with the hemiparetic leg (or
      randomly selected leg for the control group) in postures that resemble stages of
      gait. The involuntary knee torques were also recorded although no feedback or
      instructions were given. RESULTS: In the toe-off and midswing postures, the
      stroke group had a significant torque bias toward extension and adduction,
      whereas the control group had a symmetric torque space. The stroke group also
      produced significantly smaller torques than the control group in the flexion and
      abduction/flexion directions. Finally, the stroke group displayed abnormal
      coupling of knee extension with hip adduction, unique to the toe-off position.
      CONCLUSIONS: Whereas gait abnormalities after stroke have been attributed to a
      number of factors, including sagittal plane strength impairments at the hip,
      knee, and ankle, our findings indicate that neuromechanical changes after stroke
      may play a significant role in determining the nature of the movement
      abnormality. Specifically, abnormal hip adduction and knee extension torque
      coupling was observed, in addition to direction-specific hip torque weakness.
      Future studies are needed to delineate the differential contributions of each
      potential factor to gait abnormalities. Understanding the underlying
      neuromechanical changes after stroke may aid the development of rehabilitation
      strategies.

PMID- 18063825
TI  - Stroke incidence and survival in the beginning of the 21st century in southern
      Sweden: comparisons with the late 20th century and projections into the future.
AB  - BACKGROUND AND PURPOSE: We report trends of stroke incidence and survival up to
      year 2001/2002 in Lund-Orup, Sweden, and projections of future stroke incidence
      in Sweden. METHODS: Lund Stroke Register, a prospective population-based study,
      included all first-ever stroke patients, between March 1, 2001 and February 28,
      2002, in the Lund-Orup health care district. Institution-based studies for 1983
      to 1985 and 1993 to 1995 were used for comparison. We calculated age-standardized
      incidence and Cox proportional hazards analysis of survival (stroke subtype, sex,
      age group, and study period in the analysis). Minimum follow-up was 46 months.
      Based on our register's stroke incidence and the official Swedish population
      projection, a projection for future stroke incidence on a national basis was
      calculated. RESULTS: We included 456 patients with first-ever stroke in
      2001/2002. The age-standardized incidence (to the European population) was 144
      per 100 000 person-years (95%CI 130 to 158) in 2001/2002, 158 (95%CI 149 to 168)
      in 1993 to 1995, and 134 (95%CI 126 to 143) in 1983 to 1985. Cox proportional
      hazard analysis indicated decreased risk of death after stroke in 2001/2002
      (hazard ratio 0.80; 95%CI 0.67 to 0.94) compared with 1993 to 1995. Up to year
      2050, the annual number of new stroke patients in Sweden may increase by 59%
      based solely on demographic changes. CONCLUSIONS: Despite possible
      underestimation of stroke incidence during the previous institution-based
      studies, the increased stroke incidence between 1983 to 1985 and 1993 to 1995 did
      not continue in 2001/2002. The long-term survival after stroke continues to
      improve. As the elderly population is growing in Sweden, stable incidence and
      increasing survival will result in a rapidly increasing prevalence of stroke
      patients in Sweden.

PMID- 18063826
TI  - Atorvastatin promotes presenilin-1 expression and Notch1 activity and increases
      neural progenitor cell proliferation after stroke.
AB  - BACKGROUND AND PURPOSE: Presenilin1 (PS1) regulates Notch1 signaling activity,
      which liberates Notch intracellular domain (NICD). Notch activation promotes
      neural progenitor cell (NPC) self-renewal in the developing brain. In this study,
      we tested whether atorvastatin-induced NPC proliferation after stroke is mediated
      by PS1 and Notch1 activation. METHODS: PS1 and NICD expressions were measured in
      retired breeder rats subjected to middle cerebral artery occlusion that were left
      untreated or treated with atorvastatin. To investigate the mechanisms of
      atorvastatin-induced NPC self-renewal, subventricular zone (SVZ) neurosphere
      culture and knockdown of Notch1 gene expression by short interfering RNA were
      used. SVZ neurosphere formation, cell proliferation, real-time polymerase chain
      reaction, and Western blotting were performed. RESULTS: Atorvastatin
      significantly increased the numbers of newly generated neuroblasts and promoted
      PS1 and NICD expression in the ipsilateral and homologous contralateral SVZ
      compared with saline-treated control rats. Increased SVZ neurosphere formation
      and cell proliferation were found in cultured neurospheres derived from normal
      rat and poststroke rat SVZs treated in vitro with atorvastatin compared with
      untreated neurospheres (P<0.05). Atorvastatin significantly increased PS1 and
      hairy and enhancer of split1 (Hes1) gene expression in cultured SVZ neurospheres.
      Inhibition of PS1 significantly decreased NICD expression. Short interfering RNA
      knockdown of Notch1 expression, decreased NPC proliferation, and NICD and hairy
      and enhancer of split1 expression in cultured neurosphere cells. CONCLUSIONS:
      These data indicate that atorvastatin increases the NPC pool in older rats and
      that it also upregulates PS1 expression and Notch1 signaling activity, which in
      turn, facilitate an increase in SVZ NPC proliferation.

PMID- 18063827
TI  - Overexpression of dimethylarginine dimethylaminohydrolase inhibits asymmetric
      dimethylarginine-induced endothelial dysfunction in the cerebral circulation.
AB  - BACKGROUND AND PURPOSE: Asymmetric dimethylarginine (ADMA) is an endogenous
      inhibitor of nitric oxide synthase (NOS). An elevation of plasma ADMA levels is
      associated with cardiovascular disease. ADMA is hydrolyzed by dimethylarginine
      dimethylaminohydrolases (DDAHs). The goal of this study was to determine whether
      overexpression of human DDAH-1 in transgenic (DDAH-1-Tg) mice inhibits the
      vascular effects of ADMA. METHODS: Using nontransgenic (non-Tg) and DDAH-1-Tg
      mice, we compared responses of the carotid artery and aorta (in vitro) and of the
      cerebral arterioles (in vivo) in the absence or presence of ADMA. DDAH-1
      expression and plasma levels of ADMA were also measured. RESULTS: Western
      blotting indicated that vascular expression of DDAH-1 was increased markedly in
      DDAH-1-Tg mice. Plasma levels of ADMA were reduced by approximately 50% in DDAH-1
      Tg mice compared with non-Tg mice (0.19+/-0.02 vs 0.37+/-0.04 micromol/L,
      P<0.05). Contraction of the aorta to nitro-l-arginine methyl ester (an inhibitor
      of NOS), an index of basal production of NO, was increased in DDAH-1-Tg mice
      compared with controls (50+/-4% vs 34+/-4%, P<0.05). Relaxation of the carotid
      artery to acetylcholine (an endothelium-dependent agonist) was enhanced in DDAH-1
      Tg animals compared with control mice (relaxation of 74+/-6% vs 59+/-5%,
      respectively, in response to 10 micromol/L acetylcholine, P<0.05). ADMA (100
      micromol/L) impaired the vascular response to acetylcholine in both non-Tg and
      DDAH-1-Tg mice, but the relative difference between the 2 strains remained.
      Responses to the endothelium-independent NO donor nitroprusside were similar in
      all groups. In vivo, ADMA (10 micromol/L) reduced responses of the cerebral
      arterioles to acetylcholine by approximately 70% in non-Tg mice (P<0.05), and
      this inhibitory effect was largely absent in DDAH-1-Tg mice. CONCLUSIONS: These
      findings provide the first evidence that overexpression of DDAH-1 increases basal
      levels of vascular NO and protects against ADMA-induced endothelial dysfunction
      in the cerebral circulation.

PMID- 18063828
TI  - Impact of preexisting depression on length of stay and discharge destination
      among patients hospitalized for acute stroke: linked register-based study.
AB  - BACKGROUND AND PURPOSE: There exists limited knowledge regarding the relation
      between depression and healthcare utilization in stroke patients. The objective
      of this register-based study was to examine the impact of having preexisting
      depression at the time of hospital admission for acute stroke on length of
      hospital stay and discharge destination. METHODS: Data from a general-practice
      database were linked to those of a hospital database to identify patients
      hospitalized for stroke and were used to categorize these patients into 3 groups
      based on preexisting mental health (MH) status at admission, ie, those with
      preexisting depression, those with another preexisting MH condition, and those
      without any preexisting MH condition. Multilevel analyses controlling for several
      potentially important covariates were performed to estimate the associations
      under study. RESULTS: Both patients with preexisting depression (n=41) and those
      with another preexisting MH condition (n=62) did not differ significantly from
      patients without any preexisting MH condition (n=211) regarding length of
      hospital stay for acute stroke. Among patients who survived hospitalization,
      those with preexisting depression had significantly higher odds of being
      discharged to an institution instead of their home than did patients without any
      preexisting MH condition. Having another preexisting MH condition had no
      significant effect on discharge destination. CONCLUSIONS: Having preexisting
      depression at admission seems to be a relevant factor in determining discharge to
      institutional care after acute stroke hospitalization. Further research is needed
      to determine the mechanism(s) through which preexisting depression decreases the
      chances of being discharged to home.

PMID- 18063829
TI  - Rapid assessment of perfusion-diffusion mismatch.
AB  - BACKGROUND AND PURPOSE: For MR perfusion-diffusion (PWI-DWI) mismatch to become
      routine in thrombolysis patient selection, rapid and reliable assessment tools
      are required. We examined interrater variability in PWI/DWI volume measurements
      and developed a rapid assessment tool based on the Alberta Stroke Program Early
      CT Scores (ASPECTS) system. METHODS: DWI and PWI were performed in 35 patients
      with stroke <6 hours after symptom onset. DWI lesion and PWI (time to peak)
      volumes were measured with planimetric techniques by 4 raters and the 95% limits
      of agreement calculated. ASPECT scores were assessed separately by 4
      investigators (2 experienced and 2 inexperienced) for DWI (MR DWI scores) and PWI
      (MR time to peak scores). MR mismatch scores were calculated as MR DWI-MR time to
      peak scores. RESULTS: Interobserver variability was much greater for PWI (95%
      limit of agreement=+/-72.3 mL) than for DWI (95% limit of agreement=+/-12.6 mL).
      A semiautomated PWI volume (time to peak+2 s) was therefore used to calculate
      mismatch volume. MR mismatch scores >or=2 predicted 20% PWI-DWI mismatch by
      volume with mean 78% sensitivity (range, 72% to 84%) and 88% specificity (range,
      83% to 90%). There was excellent agreement on mismatch classification using MR
      mismatch scores between experienced raters (weighted kappa scores of 0.94) with
      agreement in 34 of 35 cases. Agreement was less consistent between inexperienced
      raters (weighted kappa=0.49, 28 of 35 cases). CONCLUSIONS: Variability in
      planimetric mismatch measurements arises primarily from differences in PWI volume
      assessment. High specificity and interrater reliability may make MR mismatch
      scores an ideal rapid screening tool for potential thrombolysis patients.

PMID- 18063830
TI  - Level and value of circulating endothelial progenitor cells in patients after
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Endothelial progenitor cells (EPCs) migrate from bone
      marrow to systemic circulation in response to tissue ischemia where they
      differentiate into mature endothelial cells for angiogenesis in situ. This study
      tested the hypothesis that the level of circulating EPCs is substantially
      increased and predictive of prognostic outcomes after acute ischemic stroke (IS).
      METHODS: The level of circulating EPCs (staining markers: CD31/CD34 [E(1)],
      CD62E/CD34 [E(2)], and KDR/CD34 [E(3)]) were examined using flow cytometry at 48
      hours after acute IS in 138 consecutive patients. The EPC level was also
      evaluated once in 20 healthy volunteers and in 40 at-risk control subjects.
      RESULTS: Level of circulating EPCs (E(1-3)) was significantly higher in patients
      with IS than in at-risk control subjects (P<0.05). Additionally, EPC (E(1-3))
      level was significantly lower in patients with severe neurological impairment
      (defined as a score >or=12 on the National Institutes of Health Stroke Scale)
      than in patients with less severe impairment (National Institutes of Health
      Stroke Scale < score 12) at 48 hours after IS (P<0.0001). Moreover, the EPC
      (E(3)) level was strongly correlated with improved National Institutes of Health
      Stroke Scale >or=4 on day 21 after IS (P=0.0004). Furthermore, low circulating
      EPC level was independently predictive of severe neurological impairment
      (National Institutes of Health Stroke Scale >or=12) at 48 hours (E(1-3)) and
      combined major adverse clinical outcomes (defined as recurrent IS, any cause of
      death, or National Institutes of Health Stroke Scale of >or=12) on day 90 (E(1))
      after IS (P<0.001). CONCLUSIONS: Level of circulating EPCs is independently
      predictive of prognosis after IS.

PMID- 18063831
TI  - Association between apolipoprotein E genotype and carotid intima-media thickness
      may suggest a specific effect on large artery atherothrombotic stroke.
AB  - BACKGROUND AND PURPOSE: Apolipoprotein E genotype (APOE) influences cholesterol
      levels and ischemic heart disease. Although there is no convincing overall
      association with ischemic stroke, APOE may influence large artery
      (atherothrombotic) stroke, for which carotid intima-media thickness (CIMT) is an
      informative intermediate phenotype. We therefore performed a systematic review
      and meta-analysis of the association between APOE and CIMT. METHODS: We sought
      all published studies assessing the association between APOE and CIMT. From each
      study, we extracted available data on study methods, subjects' characteristics,
      and mean (and standard deviation) CIMT for each genotype or genotype group. We
      calculated study-specific and random effects pooled differences in mean CIMT
      between genotype groups, and assessed heterogeneity between studies and
      predefined subgroups using I(2) and chi(2) statistics. RESULTS: Meta-analysis of
      22 published studies (30,879 subjects) showed a significant association between
      APOE and CIMT (pooled mean difference epsilon 4- versus epsilon 2-allele
      containing genotypes 46 microm, 95% CI 29 to 62, P<0.00001). We found evidence of
      small study (mainly publication) bias, with a diminished (but still highly
      statistically significant) association in studies of >1000 subjects (pooled mean
      difference 17 microm, 95% CI 12 to 23, P<0.00001). The association was larger
      among high vascular risk and eastern Asian populations, but this may simply
      reflect the smaller size of these studies. CONCLUSIONS: Our results show a clear
      association of APOE with CIMT, even though publication bias means that this is
      overestimated by the published literature. These findings suggest the possibility
      of a specific association with large artery ischemic stroke.

PMID- 18063832
TI  - Oxidative stress and matrix metalloproteinase-9 in acute ischemic stroke: the
      Biomarker Evaluation for Antioxidant Therapies in Stroke (BEAT-Stroke) study.
AB  - BACKGROUND AND PURPOSE: Experimental stroke studies indicate that oxidative
      stress is a major contributing factor to ischemic cerebral injury. Oxidative
      stress is also implicated in activation of matrix metalloproteinases (MMPs) and
      blood-brain barrier injury after ischemia-reperfusion. Plasma biomarkers of
      oxidative stress may have utility as early indicators of efficacy in Phase 2
      trials of antioxidant therapies in human stroke. To date, a valid biomarker has
      been unavailable. We measured F2-isoprostanes (F2IPs), free-radical induced
      products of neuronal arachadonic acid peroxidation, in acute ischemic stroke. We
      aimed to determine the change in plasma F2IP levels over time and relationship
      with plasma MMP-9 in tPA-treated and tPA-untreated stroke patients. METHODS: We
      performed a case-control study of consecutive ischemic stroke patients (25 tPA
      treated and 27 tPA-untreated) presenting within 8 hours of stroke onset. Controls
      were individuals without prior stroke from a primary care clinic network serving
      the source population from which cases were derived. Infarct volume was
      determined on acute diffusion-weighted MRI (DWI) performed within 48 hours using
      a semi-automated computerized segmentation algorithm. Phlebotomy was performed at
      <8 hours, 24 hours, 2 to 5 days, and 4 to 6 weeks. F2IPs were measured by gas
      chromatography/mass spectrometry and MMP-9 by ELISA. Prestroke antioxidant
      dietary intake was measured by the 24-hour recall method. RESULTS: In 52 cases
      and 27 controls, early (median 6 hours postonset) F2IPs were elevated in stroke
      cases compared with controls (medians 0. 041 versus 0.0295 pg/mL, P=0.012). No
      difference in F2IPSs was present at later time points. Early plasma F2IPs
      correlated with MMP-9 in all patients (P=0.01) and the tPA-treated subgroup
      (P=0.02). No correlation was found with NIHSS, DWI infarct volume, 90-day Rankin
      score, or C-reactive protein (P>0.05 for all). CONCLUSIONS: In early human stroke
      we found evidence of increased oxidative stress and a relationship with MMP-9
      expression, supporting findings from experimental studies.

PMID- 18063833
TI  - Are steroids useful to treat cerebral venous thrombosis?
AB  - BACKGROUND AND PURPOSE: No randomized controlled trial has evaluated the efficacy
      of steroids in acute cerebral venous thrombosis (CVT). We aimed to analyze the
      effect of steroids on the outcome of patients in the International Study on
      Cerebral Veins and Dural Sinus Thrombosis (ISCVT). METHODS: ISCVT is a
      prospective observational study that included 624 CVT patients. Death or
      dependence at 6 months was compared between cases (patients treated with
      steroids) and controls (patients not treated with steroids), using 3 designs: (1)
      Matched case-control study (each case matched with a control for prognostic
      factors); (2) Nonmatched case-control study of the ISCVT cohort; (3) Case-control
      study in different strata according to the number of poor prognostic variables in
      each patient. RESULTS: One hundred and fifty (24%) patients were treated with
      steroids. (1) In the matched case-control study, poor outcome was similar in the
      two groups of patients (26/146 versus 17/149, OR=1.7; 95% CI 0.9 to 3.3,
      P=0.119). (2) In the ISCVT cohort, no significant difference in poor outcomes was
      found whether patients were treated with steroids or not (26/146 versus 60/469,
      OR=1.5; 95% CI 0.9 to 2.4). Patients without parenchymal lesions treated with
      steroids had worse prognosis than those treated without steroids (8/45 versus
      9/184, OR=4.2, 95% CI 1.6 to 11.6, P=0.008). (3) Treatment with steroids was not
      associated with a better outcome in any strata of patients according to the
      number of poor prognostic factors. CONCLUSIONS: Steroids in the acute phase of
      CVT were not useful and were detrimental in patients without parenchymal cerebral
      lesions. These results do not support the use of steroids in CVT (evidence level
      III).

PMID- 18063834
TI  - Avoiding interference: adult attachment and emotional processing biases.
AB  - The present study investigated attachment-related differences in emotional
      processing biases. Consistent with the proposal that avoidant individuals limit
      attention to potentially distressing information, attachment avoidance was
      associated with reductions in emotional Stroop (ES) interference for attachment
      related words (e.g., intimate, loss). These biases were strongest among
      individuals who were currently in a romantic relationship, suggesting that being
      in a close relationship may activate avoidant defensive strategies. In addition,
      avoidant attentional biases were attenuated under cognitive load, suggesting that
      inhibiting attention to attachment-related information requires cognitive effort.
      Finally, avoidance was unrelated to ES performance for emotional, nonattachment
      related words, demonstrating the specificity of these attentional biases. The
      present findings suggest that avoidant individuals can inhibit attention to
      potentially threatening information, that this ability requires cognitive effort,
      and that relationship status may be an important moderator of avoidant defensive
      strategies. The implications of these strategies for emotional functioning and
      well-being are discussed.

PMID- 18063835
TI  - Forgiveness, feeling connected to others, and well-being: two longitudinal
      studies.
AB  - In two studies, the authors investigated the associations between interpersonal
      forgiveness and psychological well-being. Cross-sectional and prospective
      multilevel analyses demonstrated that increases in forgiveness (measured as
      fluctuations in individuals' avoidance, revenge, and benevolence motivations
      toward their transgressors) were related to within-persons increases in
      psychological well-being (measured as more satisfaction with life, more positive
      mood, less negative mood, and fewer physical symptoms). Moreover, forgiveness was
      more strongly linked to well-being for people who reported being closer and more
      committed to their partners before the transgression and for people who reported
      that their partners apologized and made amends for the transgression. Evidence
      for the reverse causal model, that increases in well-being were related to
      increases in forgiveness, was also found. However, changes in feelings of
      closeness toward the partner appeared to account for the associations of
      forgiveness with well-being, but not vice versa.

PMID- 18063836
TI  - Estrogen determines sex differences in airway responsiveness after allergen
      exposure.
AB  - The female hormone estrogen is an important factor in the regulation of airway
      function and inflammation, and sex differences in the prevalence of asthma are
      well described. Using an animal model, we determined how sex differences may
      underlie the development of altered airway function in response to allergen
      exposure. We compared sex differences in the development of airway
      hyperresponsiveness (AHR) after allergen exposure exclusively via the airways.
      Ovalbumin (OVA) was administered by nebulization on 10 consecutive days in BALB/c
      mice. After methacholine challenge, significant AHR developed in male mice but
      not in female mice. Ovariectomized female mice showed significant AHR after 10
      day OVA inhalation. ICI182,780, an estrogen antagonist, similarly enhanced airway
      responsiveness even when administered 1 hour before assay. In contrast, 17beta
      estradiol dose-dependently suppressed AHR in male mice. In all cases, airway
      responsiveness was inhibited by the administration of a neurokinin 1 receptor
      antagonist. These results demonstrate that sex differences in 10-day OVA-induced
      AHR are due to endogenous estrogen, which negatively regulates airway
      responsiveness in female mice. Cumulatively, the results suggest that endogenous
      estrogen may regulate the neurokinin 1-dependent prejunctional activation of
      airway smooth muscle in allergen-exposed mice.

PMID- 18063837
TI  - Effects of albuterol isomers on the contraction and Ca2+ signaling of small
      airways in mouse lung slices.
AB  - The beta(2)-adrenergic agonist, albuterol, is used as a bronchodilator by
      patients with asthma and consists of a racemic mixture of (R)- and (S)-albuterol.
      However, the action of the individual enantiomers is poorly understood.
      Consequently, we investigated the effects of (R)-, (S)- and racemic-albuterol on
      airway smooth muscle cell (SMC) contraction and Ca(2+) signaling in mouse lung
      slices with phase-contrast and confocal microscopy. (R)-albuterol relaxed airways
      contracted with methacholine (MCh) in a dose-dependent manner. By contrast, (S)
      albuterol had no effect on airways. (R)-albuterol had a greater relaxant effect
      than a double concentration of racemic albuterol. Because MCh-induced contraction
      of airway SMCs is mediated by Ca(2+) oscillations and an increase in Ca(2+)
      sensitivity, the effects of albuterol on these responses were examined. Both (R)-
      and racemic albuterol decreased the frequency of the MCh-induced Ca(2+)
      oscillations by a similar amount. However, (R)-albuterol was more effective than
      racemic albuterol in decreasing the Ca(2+) sensitivity of the airway SMCs in
      "model" lung slices with a clamped [Ca(2+)](i). In contrast, (S)-albuterol had no
      effect on the Ca(2+) oscillations or the Ca(2+) sensitivity. In conclusion, (R)
      albuterol consistently induced a greater airway relaxation than racemic
      albuterol, and (S)-albuterol appears to be responsible for this reduced efficacy.

PMID- 18063838
TI  - Lung lining fluid glutathione attenuates IL-13-induced asthma.
AB  - GGT(enu1) mice, deficient in gamma-glutamyl transferase and unable to metabolize
      extracellular glutathione, develop intracellular glutathione deficiency and
      oxidant stress. We used intratracheal IL-13 to induce airway inflammation and
      asthma in wild-type (WT) and GGT(enu1) mice to determine the effect of altered
      glutathione metabolism on bronchial asthma. WT and GGT(enu1) mice developed
      similar degrees of lung inflammation. In contrast, IL-13 induced airway
      epithelial cell mucous cell hyperplasia, mucin and mucin-related gene expression,
      epidermal growth factor receptor mRNA, and epidermal growth factor receptor
      activation along with airway hyperreactivity in WT mice but not in GGT(enu1)
      mice. Lung lining fluid (extracellular) glutathione was 10-fold greater in
      GGT(enu1) than in WT lungs, providing increased buffering of inflammation
      associated reactive oxygen species. Pharmacologic inhibition of GGT in WT mice
      produced similar effects, suggesting that the lung lining fluid glutathione
      protects against epithelial cell induction of asthma. Inhibiting GGT activity in
      lung lining fluid may represent a novel therapeutic approach for preventing and
      treating asthma.

PMID- 18063839
TI  - Basal cells of differentiated bronchial epithelium are more susceptible to
      rhinovirus infection.
AB  - We used an in vitro model of differentiated tracheobronchial epithelium to
      analyze the susceptibility of different cell types to infection with rhinoviruses
      (RVs). Primary cells from control subjects were cultured in an air-liquid
      interface to form differentiated epithelia. Suprabasal and basal fractions were
      separated after trypsin digestion, and cell suspensions were infected with
      serotypes RV16 and RV1A. These cell fractions were analyzed for expression of
      viral capsid protein VP2 (flow cytometry), viral replication (real-time PCR),
      cytokeratin-14, and intercellular adhesion molecule-1 (ICAM-1). Compared with
      suprabasal fraction, basal cells had increased percentages of cells staining
      positive for VP2 (RV1A: 37.8% versus 9.1%, P < 0.01; RV16: 12.0 versus 3.0%, P <
      0.05). The average number of viral RNA copies per cell was also higher in basal
      cells (2.2- and 2.4-fold increase in RV1A- and RV16-infected cells, respectively)
      compared with suprabasal cells. Furthermore, ICAM-1 was expressed by 33.3% of
      basal cells, compared with 8.1% of suprabasal cells (P < 0.05). Finally, in
      culture models of epithelial injury (detached suprabasal cells or scratched
      surface), there was significantly greater replication of RV1A compared with
      intact cell layer. These findings demonstrate that basal cells are more
      susceptible to RV infection than suprabasal cells. For major group RV, this may
      be in part due to increased expression of ICAM-1; however, minor group RV also
      replicated more effectively in basal cells. These results suggest the possibility
      that epithelial cell differentiation is associated with the maturation of
      antiviral defense mechanisms.

PMID- 18063840
TI  - Derivation of lung epithelium from human cord blood-derived mesenchymal stem
      cells.
AB  - RATIONALE: Recent studies have suggested that both embryonic stem cells and adult
      bone marrow stem cells can participate in the regeneration and repair of diseased
      adult organs, including the lungs. However, the extent of airway epithelial
      remodeling with adult marrow stem cells is low, and there are no available in
      vivo data with embryonic stem cells. Human umbilical cord blood contains both
      hematopoietic and nonhematopoietic stem cells, which have been used clinically as
      an alternative to bone marrow transplantation for hematologic malignancies and
      other diseases. OBJECTIVES: We hypothesized that human umbilical cord blood stem
      cells might be an effective alternative to adult bone marrow and embryonic stem
      cells for regeneration and repair of injured airway epithelium. METHODS: Human
      cord blood was obtained from normal deliveries at the University of Vermont.
      Cultured plastic adherent cells were characterized as mesenchymal stem cells
      (MSCs) by flow cytometry and differentiation assays. Cord blood-derived MSCs (CB
      MSCs) were cultured in specialized airway growth media or with specific growth
      factors, including keratinocyte growth factor and retinoic acid. mRNA and protein
      expression were analyzed with PCR and immunofluorescent staining. CB-MSCs were
      systematically administered to immunotolerant, nonobese diabetic/severe combined
      immunodeficiency (NOD-SCID) mice. Lungs were analyzed for presence of human
      cells. MEASUREMENTS AND MAIN RESULTS: When cultured in specialized airway growth
      media or with specific growth factors, CB-MSCs differentially expressed Clara
      cell secretory protein (CCSP), cystic fibrosis transmembrane conductance
      regulator (CFTR), surfactant protein C, and thyroid transcription factor-1 mRNA,
      and CCSP and CFTR protein. Furthermore, CB-MSCs were easily transduced with
      recombinant lentiviral vectors to express human CFTR. After systemic
      administration to immunotolerant, NOD-SCID, mice, rare cells were found in the
      airway epithelium that had acquired cytokeratin and human CFTR expression.
      CONCLUSIONS: CB-MSCs appear to be comparable to MSCs obtained from adult bone
      marrow in ability to express phenotypic markers of airway epithelium and to
      participate in airway remodeling in vivo.

PMID- 18063842
TI  - TNF signaling: early events and phosphorylation.
AB  - Tumor necrosis factor-alpha (TNF) is a major mediator of apoptosis as well as
      immunity and inflammation. Inappropriate production of TNF or sustained
      activation of TNF signaling has been implicated in the pathogenesis of a wide
      spectrum of human diseases, including cancer, osteoporosis, sepsis, diabetes, and
      autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and
      inflammatory bowel disease. TNF binds to two specific receptors, TNF-receptor
      type I (TNF-R1, CD120a, p55/60) and TNF-receptor type II (TNF-R2, CD120b,
      p75/80). Signaling through TNF-R1 is extremely complex, leading to both cell
      death and survival signals. Many findings suggest an important role of
      phosphorylation of the TNF-R1 by number of protein kinases. Role of TNF-R2
      phosphorylation on its signaling properties is understood less than TNF-R1. Other
      cellular substrates as TRADD adaptor protein, TRAF protein family and RIP kinases
      are reviewed in relation to TNF receptor-mediated apoptosis or survival pathways
      and regulation of their actions by phosphorylation.

PMID- 18063841
TI  - Low-level fiber-induced radiographic changes caused by Libby vermiculite: a 25
      year follow-up study.
AB  - RATIONALE: From 1921 to 1990, vermiculite ore from Libby, Montana, was shipped
      worldwide for commercial and residential use. A 1980 study of a manufacturing
      facility using Libby vermiculite was the first to demonstrate a small but
      significant prevalence of pleural chest radiographic changes associated with
      amphibole fibers contained in the ore. OBJECTIVES: This follow-up study of the
      original cohort evaluated the extent of radiographic changes and cumulative fiber
      exposure (CFE) 25 years after cessation of exposure. METHODS: From the original
      cohort of 513 workers, 431 (84%) were living and available for participation and
      exposure reconstruction. Of these, 280 (65%) completed both chest radiographs and
      interviews. Primary outcomes were pleural and/or interstitial changes.
      MEASUREMENTS AND MAIN RESULTS: Pleural and interstitial changes were demonstrated
      in 80 (28.7%) and 8 (2.9%) participants, respectively. Of those participants with
      low lifetime CFE of less than 2.21 fiber/cc-years, 42 (20%) had pleural changes.
      A significant (P < 0.001) exposure-response relationship of pleural changes with
      CFE was demonstrated, ranging from 7.1 to 54.3% from the lowest to highest
      exposure quartile. Removal of individuals with commercial asbestos exposure did
      not alter this trend. CONCLUSIONS: This study indicates that exposure within an
      industrial process to Libby vermiculite ore is associated with pleural thickening
      at low lifetime CFE levels. The propensity of the Libby amphibole fibers to
      dramatically increase the prevalence of pleural changes 25 years after cessation
      of exposure at low CFE levels is a concern in view of the wide national
      distribution of this ore for commercial and residential use.

PMID- 18063843
TI  - QT interval prolongation and decreased heart rates after intravenous bolus
      oxytocin injection in male and female conscious rabbits.
AB  - The aim of this study was to evaluate changes in heart rate (HR), QT and RR
      intervals and corrected QT (QTc) values in conscious male and female New Zealand
      rabbits which intravenously received oxytocin (OXT) at different dosages. Animals
      were divided into 6 equal groups: group I (n = 6 male, received 0.75 U OXT per
      animal); group II (n = 6 male, received 1.5 U OXT per animal); group III (n = 6
      male, received 3 U OXT per animal); group IV (n = 6 female, received 0.75 U OXT
      per animal); group V (n = 6 female, received 1.5 U OXT per animal); group VI (n =
      6 female, received 3 U OXT per animal). ECG recording were taken from all animals
      before injection and then at 2, 4, 6, 8, 10, 15 and 20 min of OXT administration.
      QT and RR intervals obtained at 2 min of OXT administration were significantly
      prolonged in all groups (p < 0.05) with one exception that is the 1.5 U OXT
      injected female group where only QT interval did not change. The prolongation of
      QT and RR intervals persisted for 20 min in 1.5 U OXT injected male group while
      only QT interval prolongation was obvious for 20 min in 3 U OXT injected female
      group as for the other groups the prolonged interval were observed for 8-10 min
      and then returned to baseline values. Generally, a significant prolongation of
      QTc was noticed in both male and female rabbits at the 2 and 4 min in all groups
      and bradycardia was noticed at 2 min of OXT administration in all groups. Heart
      beats returned to normal values in all groups after 8 min of OXT administration.
      The change of HR, RR, QT and QTc was gender- but not dose-dependent (p < 0.001).
      The male rabbits were more sensitive to OXT effect then female rabbits. In
      conclusion, OXT used in therapeutic dosages decreased heart rate and prolonged QT
      and QTc intervals. Although cardiovascular effect of OXT are of short duration,
      its use in patient with risk factors for malignant arrhythmias requires more
      attention.

PMID- 18063845
TI  - Impairment of the insulinotropic effect of gastric inhibitory polypeptide (GIP)
      in obese and diabetic rats is related to the down-regulation of its pancreatic
      receptors.
AB  - The association of obesity with type 2 diabetes mellitus has been recognized for
      years. In type 2 diabetes, there is a possibility that an important part of the
      impaired insulin secretion is due to the gastric inhibitory polypeptide (GIP)
      hormone. This study investigated changes that occur in the pancreatic GIP
      receptors' (GIP-Rs) expression and in GIP secretion in obese and type 2 diabetic
      rats and its relation to plasma glucose and insulin levels during oral glucose
      tolerance test (OGTT) compared to control rats. During the first 20 min of the
      OGTT, both the obese and the diabetic rats had a significant increase in the
      glucose excursion and a significant decrease in early-insulin secretion compared
      to the control group, with more prominent changes in the diabetic group. The
      obese rats had a significant increase in fasting GIP level and in the incremental
      change of GIP from 0 to 20 min (GIP Delta 0-20: 60.1 + or - 6.66 pmol/l) compared
      to that of the control (33.96 + or - 4.69 pmol/l) and the diabetic (29.34 + or -
      2.62 pmol/l) group, which were not significantly different from each other.
      However, there was a significant decrease in GIP-Rs expression in both the obese
      (88.07 + or - 10.36 microg/ml) and diabetic (87.51 + or - 4.72 microg/ml) groups
      compared to the control group (120.35 + or - 8.06 microg/ml). During the second
      hour of the OGTT, plasma GIP was decreasing in all groups, however, the obese
      group had a significant hyperinsulinemia compared to the other two groups.
      Moreover, the diabetic group had a significantly lower plasma insulin level until
      the 90 min interval and thereafter it showed a non-significant difference
      compared to the control group. In conclusion, both obese and diabetic rats had an
      impaired early-phase insulinotropic effect of GIP due to impaired gene expression
      of GIP-Rs which could be a potential target to prevent transition of obesity to
      diabetes and to improve insulin secretion in the latter.

PMID- 18063844
TI  - Evaluation of novel microtubules interfering agents myoseverin, tubulyzine and
      E2GG in primary cultures of rat hepatocytes.
AB  - We investigated the effects of novel microtubules interfering agents (MIAs) in
      primary cultures of rat hepatocytes. Cells were treated for 24 h with a known
      compound colchicine and newly synthesized derivatives myoseverin, tubulyzine, and
      E2GG. We examined the effects of MIAs on microtubules network integrity and on
      the polymerization capability of isolated tubulin. All tested MIAs inhibited
      microtubules assembly with the following IC(50) values: tubulyzine (4.4 + or -
      0.9 micromol/l), myoseverin (7.0 + or - 0.8 micromol/l), E2GG (16 + or - 2
      micromol/l), colchicine (2.0 + or - 0.4 micromol/l). The potency of MIAs to
      perturb microtubular network integrity (monitored by immune-histochemistry)
      increased in the order tubulyzine < myoseverin < E2GG < colchicine. We described
      recently deleterious effects of MIAs on the expression of drug metabolizing
      enzymes, including CYP1A1. Here we observed inhibitory effects of novel MIAs on
      dioxin-inducible expression of CYP1A1 mRNA in rat hepatocytes. We conclude that
      novel MIAs exert analogical biological response as classical MIAs such as
      colchicine or nocodazole. This further supports the hypothesis that tubulin is
      the primordial target of MIAs within the cell and that perturbation of
      microtubules dynamics and/or integrity triggers the biological effects described
      here.

PMID- 18063846
TI  - Natriuretic peptides and endothelin-1 in patients undergoing coronary artery
      bypass grafting.
AB  - Off-pump coronary artery bypass grafting (CABG) is an alternative to conventional
      CABG using cardiopulmonary bypass. Off-pump technique reduces the complications
      of CABG performed with extracorporeal circulatory assistance (Lancey et al. 2000;
      Mack et al. 2004a,b). The object of this study was to compare peri- and
      postoperative time courses of vasoactive peptides - atrial natriuretic poptide
      (ANP), brain natriuretic poptide (BNP) and endothelin-1 (ET-1) in off-pump versus
      on-pump CABG. 22 patients, who underwent on-pump (group A, n = 11) or off-pump
      CABG (group B, n = 11) were studied. The peri- and postoperative time courses of
      plasma ANP and BNP were similar in both groups. A statistically significant
      difference between ET-1 plasma level 2 h after surgery in the group A and ET-1
      plasma level 2 h after surgery in the group B (2.46 + or - 1.14 pg/ml/Ht versus
      0.74 + or - 0.09 pg/ml/Ht, p < 0.0001) was found. Different CABG techniques were
      not associated with significant changes in peri- and postoperative plasma ANP and
      BNP. By contrast, plasma ET-1 significantly rose in the group A 2 h after
      surgery, indicating endothelial damage.

PMID- 18063847
TI  - Photodynamic effect on melanoma cells investigated by atomic force microscopy.
AB  - Atomic force microscopy (AFM) is a modern experimental method for imaging of
      conducting or non-conducting samples. New trends in the application of scanning
      probe microscopy (SPM) give us the ability to scan live cells directly in their
      ingenuous surroundings or in air. Our apparatus was replenished with an inverse
      optical microscope, so we could observe the position of the scanning tip in every
      individual cell. The aim of the presented study is to picture the cell surface in
      air. A dry scanner in non-contact or tapping mode was used in the biological
      application of AFM. In our work the cell line G361 was used as a biological
      sample. We imaged the cell line before and after induction of a photodynamic
      effect (PDE) by irradiation of ZnTPPS4-loaded cells with a light dose of 15
      J/cm(2). Individual cells before PDE induction had a smooth surface without
      protrusion on the entire surface. Cells after PDE induction did not have a smooth
      surface but their surface was rough with protrusion and in some places cleaved.

PMID- 18063848
TI  - Effect of the pyridoindole antioxidant stobadine on ATP-utilisation by renal Na,K
      ATPase in rats with streptozotocin-induced diabetes.
AB  - The effect of the pyridoindole antioxidant stobadine on diabetes-induced changes
      of Na,K-ATPase, especially those concerning the utilisation of its substrate ATP,
      was investigated. Sixteen weeks of streptozotocin-induced diabetes (single i.v.
      dose of streptozotocin; 55 mg/kg) was followed by decrease in the enzyme
      activity. This effect was emphasised in the presence of higher concentrations of
      substrate and in the presence of 8 mmol x l(-1) ATP it represented 20%. It might
      be a consequence of altered functional properties of Na,K-ATPase as suggested by
      20% decrease in the V(max) value along with decrease in the K(m) value by 20%.
      Administration of 0.05% (w/w) stobadine in the diet to diabetic rats improved the
      function of renal Na,K-ATPase with respect to utilisation of ATP as suggested by
      significant increase in the enzyme activity in the whole concentration range of
      ATP investigated as a consequence of V(max) elevation to the level comparable to
      absolute controls. In conclusion, stobadine may play a positive role in restoring
      the functional properties of renal Na,K-ATPase, especially concerning the
      utilisation of energy derived from hydrolysis of ATP, improving thus the
      maintenance of ionic homeostasis during diabetes.

PMID- 18063849
TI  - Pharmacological blockade of sarcoplasmic reticulum induces a negative lusitropic
      effect.
AB  - The relaxation and the inter-beat mechanical tension are termed lusitropic
      functions. It is generally assumed that they are primarily determined by Ca(2+)
      homeostasis of cardiac cell and by interactions of Ca(2+) with the contractile
      machinery. In the present study we studied the effects of various pharmacological
      interventions on the excitation-contraction coupling in right ventricular
      papillary muscles of adult rabbits at various stimulation rates. The maximal
      force of isometric contraction (MG, a.u.), the time to peak of isometric
      contraction (TTP, ms), the maximal speed of relaxation (dF/dt(relax)), the
      diastolic tension (DT, a.u.) and the total tension (MG+DT, a.u.) were measured.
      To affect excitation-contraction coupling, caffeine (5 mmol x l(-1)), ryanodine
      (1 micromol x l(-1)) and dantrolene sodium (50 micromol x l(-1)) were used.
      Whereas caffeine and ryanodine elicited a pronounced negative lusitropic effect,
      the effect of dantrolene was less dramatic with preserved frequency dependence.
      The results indicate that the key element for affecting the lusitropic functions
      is the ryanodine receptor of the sarcoplasmic reticulum (SR). The lusitropic
      effects of dantrolene, that affects cardiac excitation-contraction coupling but
      only minimally the ryanodine receptors of SR, were considerably less pronounced.
      The findings agree with the assumption that the lusitropic disturbances are
      closely related to the defects of SR ryanodine receptors of cardiac myocytes.

PMID- 18063850
TI  - Long-time alcohol intake modifies resistin secretion and expression of resistin
      gene in adipose tissue.
AB  - Elevated serum resistin is implicated in insulin resistance associated with
      obesity and type 2 diabetes mellitus. Alcohol consumption interferes with the
      nutritional status, metabolic and hormonal activity of the drinker. Impact of
      ethanol intake on resistin level and resistin metabolic effects is unknown.
      Effect of long-time (28 days) ad libitum moderate alcohol (6% ethanol solution)
      intake on serum resistin and resistin mRNA level in adipose tissue of rats (A)
      was compared to control (C) and pair-fed (PF) animals. PF rats were fed the same
      caloric amount as A rats on previous day. Alcohol consumption resulted in
      reduction of food and energy intake, decreased body mass gain, epididymal fat
      pads mass and smaller adipocytes (vs. C rats). Alcohol intake significantly
      increased serum resistin and glucose, insulinemia remained unchanged. Systemic
      insulin resistance was not proved by HOMA, QUICKI and McAuley indexes, but
      impaired insulin effect on glucose transport in isolated adipocytes was present.
      Elevated serum resistin was positively correlated with glycemia (r = 0.88, p <
      0.01) and negatively with fat cell size (r = -0.73, p < 0.05). High resistin
      level as the consequence of long-time alcohol intake could contribute to smaller
      adipocytes, higher glycemia, attenuation of insulin-stimulated glucose transport
      in adipocytes. Diminished resistin gene expression in adipose tissue of A and PF
      rats was present.

PMID- 18063851
TI  - Angiopoietin-like protein 3: development, analytical characterization, and
      clinical testing of a new ELISA.
AB  - The aim of our work was to develop an assay for the determination of angiopoietin
      like protein 3 (Angptl3) in human blood, and investigate its levels in healthy
      volunteers and donors suffer from metabolic syndrome and familiar
      hypercholesterolemia. We developed and evaluated the sandwich ELISA method for
      the quantitative determination of human Angptl3 in serum samples. We conducted
      also the pilot study on individuals with metabolic syndrome or familiar
      hypercholesterolemia and healthy probands. The following parameters were
      measured: blood pressure, waist circumference, Angptl3 serum levels, serum
      cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, insulin, glucose, A
      FABP, and BMI and Quicki insulin sensitivity index was calculated. In the study
      on 93 healthy volunteers we demonstrated that sex or age is not the determinant
      for Angptl3 serum values. Futhermore, 118 individuals with metabolic syndrome and
      200 patients with familiar hypercholesterolemia were tested and it was found that
      probands with metabolic syndrome or familiar hypercholesterolemia had higher
      Angptl3 values than healthy individuals from the first study (medians 289.5 vs.
      277.1 vs. 224.8 ng/ml, p < 0.01). All of groups did not differ in sex or age.
      Angptl3 values correlated with the systolic blood pressure, LDL and A-FABP (p <
      0.05). No connection of Angptl3 with triglycerides was found (presumably
      influences of statins, fibrates via PPARs, etc). However, we performed stepwise
      regression and found A-FABP and Angptl3 serum values as the independent markers
      for metabolic syndrome presence only (F ratio 29, p < 0.01). Then we adjusted
      Angptl3 to A-FABP (reputable metabolic syndrome marker) and recognised that
      Angptl3 is the A-FABP-independent marker. The pilot study supports the hypothesis
      about the role of Angptl3 as a new class of lipid metabolism modulator. Their
      values could be a new key predictors of metabolic syndrome. Further research is
      necessary to confirm our findings in individuals with dyslipidemia, obesity, CAD
      and different medication in order to assess Angptl3 value as a risk predictor of
      accelerated atherosclerosis.

PMID- 18063852
TI  - Monovalent currents through the T-type Cav3.1 channels and their block by Mg2+.
AB  - We have investigated the permeability of the Cav3.1 channel for Ca2+ and
      different monovalent cations and the block of the currents by Mg2+ ions. In the
      absence of extracellular divalent cations, the Cav3.1 channel was more permeable
      for Na+ than for Cs+ and impermeable for NMDG+. Monovalent currents were
      inhibited by Mg2+ of near physiological concentration by three orders of
      magnitude more effectively than the Ca2+ current. Inhibition of outward, but not
      inward current by Mg2+ was voltage-dependent. Furthermore, magnesium slowed down
      channel deactivation presumably by interacting with an open channel state.

PMID- 18063853
TI  - The effect of all-trans retinoic acid and/or colchicine on expression of rexinoid
      and thyroid hormone nuclear receptors and their coregulators in primary rat
      hepatocytes.
AB  - In the present work, the effects of colchicine (COL) and/or all-trans retinoic
      acid (ATRA) on expression of rexinoid receptors (RXRs) (alpha, beta, gamma),
      thyroid hormone receptor alpha and coregulators N-CoR, SMRT and SRC-1 mRNA in
      primary rat hepatocytes as a model of no-proliferating cells were investigated.
      Treatment with these components, either alone or in combination, induced
      differences of the expression profiles between distinct treatment groups.

PMID- 18063854
TI  - Interplay between dose and frequency of GnRH administration in determining
      pituitary gonadotropin responsiveness.
AB  - BACKGROUND/AIMS: The dose, frequency and contour of GnRH stimulation of the
      pituitary gonadotrope have been shown to be independent variables influencing
      pituitary LH secretion. The dynamic interaction between these variables during
      physiological and pathophysiological states has yet to be examined. METHODS:
      Twelve men with GnRH deficiency and idiopathic hypogonadotropic hypogonadism
      undergoing GnRH therapy participated in a series of studies in which 2 log orders
      of GnRH doses (2.5-250 ng/kg) were administered at frequencies varying from 0.5
      to 8 hourly. Pituitary responses were characterized by pulse amplitudes and
      nadirs. The relative sensitivity of the gonadotrope to GnRH was defined as that
      dose of GnRH capable of eliciting an LH pulse amplitude equal to the mean LH
      amplitude in normal men. RESULTS: As GnRH stimulation of the gonadotrope slowed
      from 0.5 to 8 hourly, pulse amplitudes of LH increased whereas mean nadirs
      decreased (p < 0.05). Unique, curvilinear dose-response curves were found for
      each frequency that demonstrated an increasing slope (p < 0.03) as the frequency
      of GnRH stimulation slowed. Thus, the relative sensitivity of the gonadotrope
      increased as the frequency of GnRH stimulation decreased over the range of
      physiological frequencies tested. CONCLUSIONS: We conclude that a delicate
      interplay exists between the dose and frequency of GnRH stimulation of the
      gonadotrope that determines pituitary LH gonadotropin responsiveness in the
      human. Slower frequencies favor increased LH release largely due to decreasing LH
      nadirs and improved sensitivity of the gonadotropes to GnRH stimulation.

PMID- 18063855
TI  - Erythropoietin-independent and -dependent stages during in vitro erythropoiesis.

PMID- 18063856
TI  - Supratherapeutic doses of angiotensin receptor blockers to decrease proteinuria
      in patients with chronic kidney disease.
AB  - An important endpoint in treating chronic kidney disease, a prevalent disease
      that can lead to kidney failure and cardiovascular disease, is reducing
      proteinuria. Proteinuria is an independent risk factor for disease progression
      and the development of cardiovascular disease and is a key factor that can be
      used to guide therapy designed to maximize kidney protection. Proteinuria is
      targeted by using pharmacologic agents that suppress the renin-angiotensin
      aldosterone system (RAAS), a regulator of intravascular volume and blood
      pressure; this has been shown to decrease proteinuria, slow disease progression,
      and improve coronary disease outcome, independent of effects on blood pressure.
      The efficacy of RAAS blockers, including angiotensin receptor blockers and
      angiotensin-converting enzyme inhibitors, may be limited by currently recommended
      doses, which are based on treatment of hypertension. Data are now emerging from
      clinical trials demonstrating that use of 'supratherapeutic doses' (doses greater
      than those approved for lowering blood pressure), compared with standard doses,
      has favorable safety, tolerability, and efficacy in reducing proteinuria in both
      diabetic and nondiabetic patients with chronic kidney disease. Supratherapeutic
      dosing may be a valuable approach for optimizing RAAS blockade and providing
      renoprotection.

PMID- 18063857
TI  - Uric acid excretion and dopamine-induced glomerular filtration response in
      patients with IgA glomerulonephritis.
AB  - BACKGROUND/AIM: It is unknown to what extent uric acid (UA) may affect vessel
      function and participate in tubulointerstitial damage. We examined the
      relationship between intrarenal vessel function and serum UA and its excretion in
      association with urinary N-acetyl-beta-D-glucosaminidase (NAG). METHODS: In 50
      IgA patients (mean age 34.7 +/- 9.3 years) and 15 controls (mean age 33.5 +/- 6.9
      years) with a creatinine clearance of 99.4 +/- 21.6 and 118.1 +/- 17.2 ml/min,
      respectively, the renal vascular function was estimated based on the dopamine
      induced glomerular filtration response (DIR; see text). The DIR was measured
      using two 120-min creatinine clearance values (before and after intravenous
      administration of 2 g/kg/min dopamine). Serum UA, triglycerides and cholesterol
      and urinary NAG (24 h) and protein and UA excretion were measured. RESULTS:
      Patients with IgA nephropathy versus controls: DIR 8.80 +/- 6.6 vs. 12.83% (p <
      0.01), NAG 7.25 +/- 3.30 vs. 4.69 +/- 1.12 U/g creatinine (p < 0.01), and
      fractional UA excretion 7.80 +/- 2.20 versus 6.29 +/- 1.80% (p < 0.01). A
      negative correlation between DIR and NAG was found; regression analysis showed a
      more prominent relationship in the patients (NAG = 9.99 - 0.29x DIR) than in the
      controls (NAG = 5.50 - 0.06x DIR). UA and urate excretion and NAG in the patients
      correlated with DIR (r = -0.39, p < 0.02; r = -0.29, p < 0.04, and r = 0.59, p <
      0.001, respectively). Multivariate analysis showed an association of DIR (R(2) =
      0.39) with NAG but not with proteinuria and UA and UA excretion; the NAG
      excretion (R(2) = 0.56) correlated significantly with UA and DIR. CONCLUSION: It
      is suggested that UA plays a role, associated with tubular dysfunction, in the
      regulation of intrarenal vessel function.

PMID- 18063858
TI  - Increase in oxidative stress but not in antioxidant capacity with advancing
      stages of chronic kidney disease.
AB  - BACKGROUND/AIMS: Increased oxidative stress in chronic kidney disease (CKD) was
      suggested to be both a cause and an effect of renal injury. However, the
      evolution of oxidant stress from early stages of renal function decline is not
      fully clear. This study aimed to determine the oxidant-antioxidant balance across
      the whole range of renal function. METHODS: A total of 116 patients with CKD (85
      predialysis patients divided into groups according to CKD stage, and 31 patients
      with end-stage renal disease (ESRD) on hemodialysis treatment), as well as 29
      healthy subjects were evaluated. Plasma levels of 15-F(2t)-isoprostane (15-F(2t)
      IsoP), a valid marker of oxidant stress, as well as total antioxidant capacity
      (TAC) and serum levels of vitamin E were measured in all participants. RESULTS:
      Plasma 15-F(2t)-IsoP levels were higher in predialysis and ESRD patients compared
      to healthy subjects and were progressively increasing with advancing CKD stages
      (p < 0.001). In contrast, plasma TAC was similar between healthy subjects and
      predialysis patients, and presented a small reduction in ESRD patients (p <
      0.001). Vitamin E levels were higher in healthy subjects compared to any other
      group (p < 0.001) and slightly higher in ESRD patients compared to predialysis
      patients (p < 0.01), but did not differ significantly between the groups of
      predialysis patients. Plasma 15-F(2t)-IsoP levels were inversely correlated with
      estimated glomerular filtration rate in predialysis patients (r = -0.65, p <
      0.001). CONCLUSIONS: This study shows that 15-F(2t)-IsoP levels increase
      progressively with advancing CKD stages, whereas TAC and vitamin E levels remain
      rather stable with the loss of renal function and change only in patients with
      ESRD.

PMID- 18063859
TI  - Study of the relationship between gene polymorphisms of paraoxonase 2 and stroke
      in a Chinese population.
AB  - BACKGROUND AND PURPOSE: The paraoxonase (PON) gene family has been demonstrated
      to be capable of preventing lipid peroxidation and could consequently exert
      antiatherosclerotic effects. Alteration of enzyme activity due to polymorphisms
      in the PON genes may influence the development of atheroma and thus affect stroke
      risk. PON2, the second member of this family, has two polymorphisms, C311S and
      G148A. Our study explores the relationship between the two polymorphisms of PON2
      and stroke. METHODS: 120 healthy individuals, 150 patients with primary cerebral
      hemorrhage and 180 patients with cerebral infarction were included in this study.
      The genotypes of PON2 were detected with polymerase chain reaction and digested
      by specific restriction enzymes. RESULTS: C311S and G148A polymorphisms of PON2
      exist in Chinese people, with the allele frequencies 0.273/0.727 for C/S and
      0.567/0.433 for G/A. No significant differences were observed in genotype and
      allele frequency between stroke patients and controls (p > 0.05). CONCLUSIONS:
      There was no significant correlation between the two tested polymorphisms of PON2
      and stroke in the Chinese population. Allele C/S and G/A might not be independent
      risk factors for stroke.

PMID- 18063860
TI  - An analysis of therapeutic, adult antibiotic prescriptions issued by dental
      practitioners in Jordan.
AB  - OBJECTIVE: The aim of this study was to determine the therapeutic adult
      antibiotics prescribed by dental practitioners working in the Jordan University
      Hospital. METHODS: Adult dental prescriptions for therapeutic antibiotics issued
      between 1 January 2003 and 31 May 2004 by dental specialists working in the
      Jordan University Hospital were included in this study. Data included the name of
      the antibiotic as well as the dose, quantity and presentation of the drug.
      Descriptive statistical analysis was carried out. RESULTS: Amoxycillin and
      metronidazole were the most commonly prescribed antibiotics, with 60% of the
      prescriptions containing amoxycillin and 39.4% containing metronidazole. 20.4% of
      the prescriptions were combination prescriptions containing metronidazole. In
      this study, long courses were observed for amoxycillin (60.5%), cephalosporins
      (21%) and metronidazole (59.7%). CONCLUSIONS: It seems that in the sample
      studied, Jordanian dental specialists have a tendency towards overprescribing
      antibiotics both in quantity and duration. This may constitute a problem
      particularly when considering the remaining sectors of less well-educated dental
      practitioners. The results will be used to increase awareness among dental
      practitioners in the field of antibiotic prescribing throughout the University of
      Jordan and the Jordanian Dental Association.

PMID- 18063861
TI  - The potential role of pemetrexed in gastrointestinal cancer.
AB  - In 2004, the new-generation multitargeted antifolate pemetrexed was approved by
      the US Food and Drug Administration for the treatment of malignant pleural
      mesothelioma and as second-line monochemotherapy for advanced non-small cell lung
      cancer. However, pemetrexed as a single agent showed activity in preclinical and
      clinical studies, as well as in many other neoplasms such as gastrointestinal
      tumors, breast, head and neck, bladder and cervix cancer. Its tolerability
      profile is very favorable since the introduction of oral folic acid and vitamin
      B(12) supplementation in December 1999, and therefore, the maximum tolerated dose
      as single agent is probably higher than the dose actually utilized in clinical
      practice. Gastrointestinal tumors are the most common malignancies in the world,
      accounting for more than 25% of all cancers. In phase II studies exploring this
      multitargeted antifolate in advanced gastrointestinal tumors, pemetrexed showed
      an interesting degree of clinical activity, encouraging further trials evaluating
      the synergism with other drugs such as oxaliplatin, irinotecan and gemcitabine.

PMID- 18063862
TI  - Intranasal mupirocin prophylaxis in elective surgery. A review of published
      studies.
AB  - BACKGROUND: Mupirocin is a natural antibiotic from Pseudomonas fluorescens which
      is available as a 2% ointment. The drug has been used mainly for topical
      treatment of the nasal vestibulum in patients carrying methicillin-resistant
      Staphylococcus aureus (MRSA). However, mupirocin is also active against
      methicillin-sensitive S. aureus. Nasal colonization with S. aureus has been
      identified as a significant risk factor for surgical site infection (SSI).
      METHODS: Randomized trials and sequential cohort studies investigating mupirocin
      nasal treatment for prophylaxis of SSI in elective surgery in comparison with
      placebo or no treatment were found by Medline review and additional manual
      search. Evaluable studies were analyzed regarding the influence of mupirocin on
      the rate of all SSIs and, specifically, of SSIs due to S. aureus. The effect in
      cardiosurgical patients was analyzed in detail. RESULTS: Four randomized and
      seven sequential open cohort studies were analyzed. Study design and mupirocin
      application schemes varied considerably. Three out of 5 studies carried out in
      cardiac surgery patients showed a significant reduction in sternotomy site
      infections. However, all three studies were open sequential cohort studies. By
      contrast, the only prospective, randomized, double-blind study in cardiosurgical
      patients showed no benefit of mupirocin. In other surgical disciplines, results
      were inconclusive or negative. Two studies specifically addressing the prevention
      of SSIs due to MRSA showed a significant effect of mupirocin on postsurgical
      infections due to this organism. CONCLUSIONS: Because of the heterogeneity of the
      studies and the variability of results, no recommendation can be given for the
      general use of mupirocin in elective surgical patients. Specifically, because of
      the negative result of a recently published high-quality study, no recommendation
      can be made for the use of mupirocin in cardiosurgical patients. By contrast,
      eradication of MRSA before surgery appears to lower SSI rates due to MRSA and is
      therefore recommended.

PMID- 18063863
TI  - Potent direct or TNF-alpha-promoted anticancer effects of 2,3-dehydrosilybin:
      comparison study with silybin.
AB  - BACKGROUND: Silybin (SIL) exhibits anticancer properties and has now entered
      clinical trials. In this study, anticancer effects of 2,3-dehydrosilybin (DHS)
      were compared with SIL either alone or in combination with TNF-alpha. METHODS:
      Cell cytotoxicity identified as apoptosis and necrosis was measured based on DNA
      fragment sizes using flow cytometry and DNA laddering. RESULTS: After 24 h
      treatment,DHS at 30-50 microM markedly induced mainly apoptosis in transformed
      HepG2 and FIB cells. DHS induced necrosis markedly in HT29 but marginally in less
      transformed EPI cells. We found that apoptosis was the major mode of cell death
      when DHS was used in combination with TNF-alpha after 6 h treatment. TNF-alpha
      could promote DHS-induced apoptosis in HepG2, HT29 and FIB cells, but not in EPI
      cells. SIL could not reproduce this TNF-alpha-enhanced apoptosis. CONCLUSION: Our
      data provide evidence for the therapeutic use of DHS as an anticancer agent which
      is more effective than SIL.

PMID- 18063864
TI  - Hyperproduction of inhibitor-susceptible TEM beta-lactamase is responsible for
      resistance of Serratia marcescens to beta-lactam-beta-lactamase inhibitor
      combinations.
AB  - BACKGROUND: Some clinical isolates of Serratia marcescens showed high-level
      resistance to expanded-spectrum cephalosporins alone and in combination with beta
      lactamase inhibitor, but the beta-lactamase extracted from these strains was
      sensitive to the inhibitors. This study examines the possible mechanisms
      responsible for the discrepancy. METHODS AND RESULTS: Three clinical isolates of
      S. marcescens bore the bla(TEM) gene coded on a plasmid. This was confirmed by
      detection of the bla gene using PCR analysis and by transferring resistance
      determinants to Escherichia coli via conjugation and transformation. All of the
      E. coli transconjugants and transformants acquired a similar level of resistance
      to penicillins and narrow-spectrum cephalosporins, and showed the reduced
      susceptibility to expanded-spectrum cephalosporins alone and in combination with
      clavulanate. As a result of the highly constitutive expression of the TEM gene,
      up to 247-690 U of beta-lactamase were produced by 10(10) cells of wild-type S.
      marcescens and the transconjugants and transformants. In the presence of 0.24
      U/ml of TEM enzyme, the minimum inhibition concentrations of cefotaxime against
      E. coli ATCC 25922 increased from 0.125 to 512 microg/ml. The TEM-type beta
      lactamase extracted from these strains was sensitive to clavulanate, and 62.2
      92.1% of its activity was inhibited after preincubation with 0.1 mM clavulanate.
      CONCLUSION: The TEM-type beta-lactamase plays a critical role in the resistance
      of S. marcescens to beta-lactams, and the hyperproduction of inhibitor
      susceptible TEM beta-lactamase is responsible for the resistance to beta-lactam
      beta-lactamase inhibitor combinations.

PMID- 18063865
TI  - Approximal caries diagnosis after data import from different digital radiography
      systems: interobserver agreement and comparison to histological hard-tissue
      sections.
AB  - AIMS: To evaluate the agreement of approximal caries diagnosis obtained with
      different types of digital radiography systems after image import into a
      reference system. METHODS: Digital radiographs were taken from 30 extracted human
      premolars with 60 diagnostic surfaces using a reference and two test systems from
      which images were imported as TIFF files. Four observers evaluated the
      radiographs using the reference software. Teeth were sectioned for histology.
      Agreement between histology and each technique was calculated using receiver
      operating characteristic (ROC) statistics. RESULTS: The areas under the ROC
      curves were not significantly different between reference and test systems.
      CONCLUSIONS: Importing files from different programs did not affect diagnostic
      accuracy.

PMID- 18063866
TI  - Prevalence of neuropsychiatric symptoms in elderly patients with dementia in
      Mungialde County (Basque Country, Spain).
AB  - BACKGROUND: Determination of the prevalence of neuropsychiatric symptoms in
      elderly patients with dementia in Mungialde. METHODS: 108 subjects with dementia,
      who participated in a door-to-door epidemiological study, were included. The 12
      item Spanish version of the Neuropsychiatric Inventory was used to evaluate these
      symptoms. RESULTS: The prevalence of at least 1 neuropsychiatric symptom was
      found to be 76.90% for all dementia types, 73.50% in patients with Alzheimer's
      disease (AD), 80% for the Parkinson-Lewy body dementia complex (PLBD), 78.60% for
      vascular dementia (VD) and 100% for frontotemporal dementia (FTD). Apathy was
      found to be the most prevalent symptom for all dementia types and in patients
      with AD (53.70 and 54.30%, respectively). The next most prevalent symptoms were
      anxiety, depression and sleep disturbances (35.20, 32.40 and 30.60%) for all
      dementia types, and anxiety and depression (32.10 and 30.90%) in patients with
      AD. The most prevalent symptoms in patients with PLBD were apathy, appetite
      changes, sleep disturbances and agitation (50% each); in patients with VD they
      were apathy, depression and anxiety (42.90% each), and in patients with FTD they
      were apathy, anxiety and aberrant motor activity (100% each). CONCLUSIONS:
      Neuropsychiatric symptoms were found to be prevalent in patients with dementia,
      irrespective of dementia type.

PMID- 18063867
TI  - Investigation of lipopolysaccharide receptor expression on human monocytes after
      major orthopaedic surgery.
AB  - BACKGROUND: The innate immune system is suppressed after major orthopaedic
      surgery, implicating a risk of septic complications. Whole-blood ex vivo testing
      with lipopolysaccharide (LPS) has shown a depression of the tumour necrosis
      factor alpha (TNF-alpha) production until 12 days postoperatively. As part of the
      innate immune system, the Toll-like receptors TLR2 and TLR4 recognize antigens
      from Gram-positive and Gram-negative bacteria, respectively. The receptors CD14
      and CD11b are involved in the LPS receptor complex, whereas human lymphocyte
      antigen (HLA)-DR binds endotoxin peptides. It is still uncertain whether the
      expression of all these receptors changes after major surgery. METHODS: In 6
      patients undergoing hip arthroplasty, we investigated three times the display of
      TLR4, TLR2, CD14, CD11b, and HLA-DR on monocytes by fluorescence-activated cell
      sorting and white blood cell counts during 12 days postoperatively. At the same
      time, the plasma levels of interleukin (IL)-1beta, IL-4, IL-6, IL-10, IL-13, and
      TNF-alpha were measured. RESULTS: There was no significant change in the
      expression of TLR4, CD14, CD11b, HLA-DR, and TLR2. Monocyte count and cytokine
      analysis did not differ from the ones pre-operatively taken. CONCLUSIONS: After
      aseptic orthopaedic surgery, there is no change in the display of the LPS
      receptor complex on monocytes. Other mechanisms have to be investigated to gain
      insight into the decrease of the TNF-alpha production capacity postoperatively.

PMID- 18063868
TI  - Effect of aging on fatty streak formation in a diet-induced mouse model of
      atherosclerosis.
AB  - Age is considered to be a major risk factor for atherosclerosis, but it is
      unclear whether age has a direct effect on susceptibility to atherosclerosis.
      Wild-type mice develop fatty streak lesions in the aortic root only when fed a
      cholate-containing high fat/cholesterol diet. To investigate the influence of age
      on fatty streak formation, young (10 weeks) and old (53 weeks) female C57BL/6
      mice were fed an atherogenic diet containing 15% fat, 1.25% cholesterol and 0.5%
      sodium cholate for 12 weeks. Atherosclerotic lesions at the aortic root were
      measured after cryosections were stained with oil red O. Results showed that old
      mice developed a comparable size of aortic lesions with young counterparts (5,600
      +/- 2,480 vs. 6,457 +/- 1,537 microm2/section; p = 0.77), although old mice had
      significantly higher plasma cholesterol levels than young mice on the atherogenic
      diet (p < 0.05). Plasma levels of soluble vascular cell adhesion molecule 1 were
      significantly higher in old mice than in young mice on both chow and Western
      diets (p < 0.005). These data indicate that age has no direct effect on
      atherosclerosis susceptibility although it is accompanied by elevations in plasma
      cholesterol and vascular cell adhesion molecule 1 levels in C57BL/6 mice. Thus,
      increased cardiovascular events with age are probably related to a progressive
      increase in plaque size rather than to an increase in atherosclerosis
      susceptibility.

PMID- 18063870
TI  - Acquired heart block: a possible complication of patent ductus arteriosus in a
      preterm infant.
AB  - A large patent ductus arteriosus (PDA) is a frequently encountered clinical
      problem in extremely low birth weight (ELBW) infants. It leads to an increased
      pulmonary blood flow and in a decreased or reversed diastolic flow in the
      systemic circulation, resulting in complications. Here we report a possible
      complication of PDA not previously published. On day 8 of life, a male ELBW
      infant (birth weight 650 g) born at a gestational age of 23 weeks and 3 days
      developed an atrioventricular block (AV block). The heart rate dropped from
      168/min to 90/min, and the ECG showed a Wenckebach second-degree AV block and
      intraventricular conduction disturbances. Echocardiography demonstrated a PDA
      with a large left-to-right shunt and large left atrium and left ventricle with
      high contractility. Within several minutes after surgical closure of the PDA, the
      heart rate increased, and after 30 min the AV block had improved to a 1:1
      conduction ratio. Echocardiography after 2 h revealed a significant decrease of
      the left ventricular and atrial dimensions. Within 12 h, the AV block completely
      reversed together with the intraventricular conduction disturbances. We suggest
      that PDA with a large left-to-right shunt and left ventricular volume overload
      may lead to an AV block in an ELBW infant. Surgical closure of the PDA may be
      indicated.

PMID- 18063869
TI  - Lower erythrocyte glutathione peroxidase activity in bronchopulmonary dysplasia
      in the first week of neonatal life.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major pulmonary complication in
      premature infants and is considered a free radical disorder. Erythrocyte catalase
      (CAT) and cellular glutathione peroxidase (c-GPx) are antioxidant enzymes that
      detoxify peroxides generated from dismutation of superoxide anion. The study goal
      was to measure enzyme activity for preterm infants during the first week of life.
      METHODS: Blood samples were collected from umbilical arterial lines or the radial
      artery of 44 preterm infants (gestational age range: 25-30 weeks) on days 0, 2,
      and 5 after delivery. Erythrocyte CAT and c-GPx activities were evaluated, while
      clinical data were obtained and the correlations of enzyme activity and BPD
      status were examined. RESULTS: There was no correlation between enzyme activity
      and gestational age or birth weight. Packed red cell transfusion did not affect
      enzyme activity and there was no difference in CAT activity between the patient
      groups. C-GPx activity from preterm infants with BPD was significantly lower than
      those of preterm infants without BPD on day 5. CONCLUSIONS: Erythrocyte c-GPx may
      play an important role in the development of BPD. Lower c-GPx activity in early
      post-natal life might be a risk factor of BPD.

PMID- 18063871
TI  - Cetuximab and chemotherapy for patients with unresectable CRC liver metastasis:
      are we changing the natural course of the disease?

PMID- 18063872
TI  - Five years of clinical experience with metronomic chemotherapy: achievements and
      perspectives.

PMID- 18063873
TI  - Ovarian cancer treatment reality in northern Rheinland-Pfalz (Germany).
      Suboptimal surgical treatment as a possible cause for inferior survival.
AB  - BACKGROUND: With regard to incidence, ovarian cancer has the highest mortality of
      all gynecologic cancers. PATIENTS AND METHODS: The treatment of 139 consecutive
      patients with epithelial ovarian cancer who were treated in an oncology group
      practice in Koblenz, Germany between 1995 and 2003 was evaluated retrospectively.
      RESULTS: The median age of the patients was 61 years (18-84). FIGO stages were
      distributed as follows: stage I 15.8%, stage II 12.9%, stage III 53.2%, stage IV
      16.5%. 49 patients (35.5%) received surgical treatment at a university hospital
      or a teaching hospital. 89 patients (64.5%) were operated on in a local or
      district hospital. A macroscopically complete resection was achieved in only 15
      patients (10.8%). The residual tumor was <1 cm in 50 patients (36%), >1 cm in 24
      patients (17.3%), and >2 cm in 49 patients (35.5%). 93.3% of the patients
      received postoperative, platinum-based chemotherapy. Median survival since first
      diagnosis was 42 months (1-346(+)). The 5-year survival rate of the whole cohort
      was only 28%. CONCLUSIONS: Overall survival in epithelial ovarian cancer was
      significantly inferior in this patient cohort compared to the results of the FIGO
      report from 2003. One possible cause may be the suboptimal surgical treatment,
      with 52.8% of the patients having a postoperative residual tumor larger than 1
      cm.

PMID- 18063874
TI  - Cost-benefit assessment of antifungal prophylaxis with liposomal amphotericin B
      in neutropenic patients.
AB  - BACKGROUND: In a recently reported randomized trial, low-dose intravenous
      liposomal amphotericin B (L-AmB) reduced the incidence of invasive fungal
      infections (20.2 vs. 4.6%, p < 0.001) in high-risk patients with hematological
      malignancies and prolonged neutropenia. PATIENTS AND METHODS: In the present
      study, we performed a retrospective cost-benefit analysis of L-AmB prophylaxis
      from the hospital perspective. RESULTS: Ninety-nine patients were eligible;
      baseline characteristics were balanced for age, sex, underlying disease, and
      duration of neutropenia. The mean duration of hospitalization was 42.9 days and
      52.3 days in the prophylaxis arm and in patients without antifungal prophylaxis,
      respectively (p = 0.096). The L-AmB prophylaxis was associated with additional
      costs of approximately EUR 630 per patient. However, total medication costs
      (including L-AmB prophylaxis) were EUR 1,219 and EUR 2,815 in patients with L-AmB
      prophylaxis and in patients in the control arm, respectively (p < 0.001). When
      involving also costs for medical procedures, the L-AmB prophylaxis reaches a
      positive net benefit of EUR 1,094 per patient. CONCLUSIONS: Our data shows that
      antifungal prophylaxis, e.g. with L-AmB, can be a safe and effective strategy to
      reduce the frequency of invasive fungal infections in selected high-risk patients
      and to obtain significant cost savings for the hospital.

PMID- 18063875
TI  - Metronomic antiangiogenic therapy with capecitabine and celecoxib in advanced
      tumor patients--results of a phase II study.
AB  - BACKGROUND: Combined therapy of continuous low dose capecitabine and high dose
      celecoxib targeting angiogenesis was used in a phase II trial to treat advanced
      cancer patients. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
      was used to monitor antiangiogenic effects. MATERIAL AND METHODS: 37 Patients (21
      men, 16 women), mean age 60 years, with advanced and progressive cancer of
      various tumor types were included. Therapy consisted of 2 x 500 mg oral
      capecitabine/ day and 2 x 400 mg oral celecoxib/day continuously until
      progression of disease. To monitor antiangiogenic effects, DCE-MRI measurements
      were performed at baseline, after 1 month, and after 3 months of therapy. Tumor
      assessment was performed according to RECIST criteria, toxicity was evaluated
      according to the CTC version 2.0 catalogue. RESULTS: Therapy was well tolerated
      without grade 3 and 4 toxicities. The mean number of treatment cycles was 4
      (range: 1-15+). Disease stabilization after 3 cycles was seen in 11 patients. 6
      patients were stable over long periods. The mean number of treatment cycles in
      this group was 10 (range: 7-15+). DCE-MRI demonstrated a reduction of tumor
      vessel permeability and blood flow in patients who reached stable disease or some
      minor regression. CONCLUSION: Continuous dosing of the combination of
      capecitabine and celecoxib was well tolerated, produced antiangiogenic effects,
      and has antitumor activity. Patients with rapid progression did not benefit.

PMID- 18063876
TI  - Cetuximab in combination with 5-fluorouracil, leucovorin and irinotecan as a
      neoadjuvant chemotherapy in patients with initially unresectable colorectal liver
      metastases.
AB  - BACKGROUND: The efficacy and safety of a combination of cetuximab, irinotecan,
      and 5-fluorouracil/leucovorin (FOLFIRI) in downsizing unresectable colorectal
      liver metastases was investigated. PATIENTS AND METHODS: Patients with
      unresectable colorectal liver metastases with or without resectable extrahepatic
      metastasis were enrolled. 23 patients initially received 400 mg/m2 of cetuximab,
      followed by a weekly infusion of 250 mg/m2 and a biweekly dose of irinotecan (180
      mg/m2), with 5-fluorouracil both by bolus (400 mg/m2) and by a 46-h infusion
      (total of 2,400 mg/m2) with leucovorin (400 mg/m2). RESULTS: The overall response
      rate was 39.1% (n = 9; 95% confidence interval (CI): 17.6-60.7%). The most common
      grade 3-4 toxicities were skin reactions (30.4%) and diarrhea (26.1%). The rate
      of conversion to resectable liver metastases was 30.4% (n = 7; 95% CI: 10.1
      50.8%). The factors found to be significantly associated with R0 resection were
      lower serum carcinoembryonic antigen levels after chemotherapy (p = 0.039), being
      chemonaive (p = 0.002), and showing a higher incidence of grade 3-4 skin toxicity
      (p = 0.011). CONCLUSIONS: Cetuximab with FOLFIRI may be an effective and safe
      treatment option for downsizing unresectable colorectal liver metastases.

PMID- 18063877
TI  - The diagnosis of C-kit negative GIST by PDGFRA staining: clinical, pathological,
      and nuclear medicine perspective.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GIST) comprise a majority of tumors
      previously diagnosed as gastrointestinal leiomyomas, leiomyoblastomas, and
      leiomyosarcomas. Although GIST may be identified by light microscopy,
      pathologists commonly employ a panel of immunohistochemical markers to confirm
      the morphological impression including anti-CD34, smooth-muscle actin, desmin,
      S100, and CD-117. However, in CD- 117 negative cases, it becomes difficult to
      diagnose GIST. This is of great importance, since the use of imatinib mesylate
      has led to a dramatic improvement in survival rates of GIST patients besides
      improved quality of life. CASE REPORT: We report the case of a 67-year-old male
      patient diagnosed as having chemotherapy-resistant metastatic leiomyosarcoma. We
      reviewed the specimen for a possible diagnosis of c-kit negative GIST. Platelet
      derived growth factor receptor-alpha (PDGFRA) immunohistochemical stain was
      recommended. The specimen was positively stained for PDGFRA. Imatinib mesylate
      (400 mg/d) was started. The patient showed an excellent response after receiving
      imatinib treatment which was documented with 18 fluoro-deoxyglucose positron
      emission tomography and computed tomography (18F-FDGPET/ CT) prior to and after
      treatment. CONCLUSION: The importance of diagnosis of c-kit negative GIST is
      emphasized while stressing the importance of PDGFRA staining besides PET/CT
      response evaluation.

PMID- 18063878
TI  - Severe hyponatremia in a patient with mantle cell lymphoma treated with
      bortezomib: a case report and review of the literature.
AB  - BACKGROUND: Hyponatremia is a known complication of cytotoxic treatment. We
      observed this side effect in a patient treated with bortezomib. This paper gives
      an overview of the literature on antineoplastic agents that have been associated
      with hyponatremia. CASE REPORT: A 77-year-old female patient with mantle cell
      lymphoma was admitted with rapidly progressive ataxia, slurred speech, and
      confusion. 43 days earlier, a second-line treatment with the proteasome inhibitor
      bortezomib had been started. Neurological examination revealed no focal deficits.
      Laboratory evaluation showed a combined electrolyte disorder with severe
      hyponatremia (sodium 112 mmol/l). RESULTS: A syndrome of inappropriate secretion
      of antidiuretic hormone (SIADH) was diagnosed, and bortezomib was identified as
      its cause. The drug was consecutively stopped. CT scan showed a complete
      remission (CR). Since, the patient has remained in a CR without further tumor
      specific treatment. CONCLUSION: Hyponatremia may be a side effect of treatment
      with bortezomib and a number of other antineoplastic agents. Because of limited
      data available, accurate incidences of this complication are not known.

PMID- 18063879
TI  - Gemtuzumab ozogamicin (mylotarg) for the treatment of acute myeloid leukemia-
      ongoing trials.
AB  - The value of the combination of gemtuzumab ozogamicin (GO) and chemotherapy for
      the treatment of acute myeloid leukemia (AML) is currently analyzed within
      clinical trials. GO (6 mg/m2) and standard-dose cytarabine (100 mg/m2) is
      evaluated for the treatment of newly diagnosed AML in elderly patients in the SAL
      phase II trial. Preliminary results of the MRC AML15 trial support the
      application of GO 3 mg/m2 with standard- and high-dose cytarabine and
      anthracyclines for the treatment of de novo AML. Within this trial the addition
      of GO seems especially of value for favorable and intermediate cytogenetic risk
      groups. The combination of GO (3 mg/m2) and high-dose cytarabine (3 g/m2) is safe
      and more effective for the treatment of refractory AML than previous combinations
      from the AMLSG study group. First results prove the possibility of allogeneic
      stem cell transplantation after GO therapy. Initial data of a phase II trial
      document the safety and efficacy profile of GO within a reduced-intensity
      conditioning protocol applying fludarabine and total body irradiation.

PMID- 18063880
TI  - Retraction. Intraoperative touch imprint cytological analysis of sentinel lymph
      nodes for the presence of metastases in breast cancer.

PMID- 18063881
TI  - Short term effects of topical cyclosporine and viscoelastic on the ocular
      surfaces in patients with dry eye.
AB  - PURPOSE: To compare the short term effects of topical 0.05% cyclosporine (CsA)
      and a mixture of 0.08% chondroitin sulfate and 0.06% sodium hyaluronate (CS-HA)
      on dry eye ocular surfaces. METHODS: 36 patients with moderate to severe dry eye
      (5 mm/5 min or less with Schirmer's test or tear break up time (BUT) less than 6
      seconds), were treated with topical application of CS-HA on one eye and CsA on
      the other 4 times a day for 6-8 weeks. BUT, Schirmer's test without anesthesia,
      and conjunctival impression cytology (CIC; goblet cell density, nucleus to
      cytoplasmic ratio, and epithelial cell morphology) were evaluated and compared
      between eyes before and after treatment (repeated measurement of ANOVA). RESULTS:
      After treatment, BUT and tear wettings were significantly prolonged in each
      group. Topical CsA treated eyes had greater increase in BUT (p=0.026); there was
      no significant difference in tear wetting (p=0.132). While the 3 parameters of
      CIC improved in both groups, goblet cell density was significantly higher in eyes
      treated with CsA (p=0.033). CONCLUSIONS: While both CS-HA and 0.05% CsA eyedrops
      improve ocular surfaces, topical CsA may have a better effect on enhancing tear
      film stability and goblet cell density.

PMID- 18063882
TI  - Visual function after primary posterior chamber intraocular lens implantation in
      pediatric unilateral cataract: stereopsis and visual acuity.
AB  - PURPOSE: To investigate the association between binocular function and vision
      after cataract removal and primary posterior chamber intraocular lens (PC-IOL)
      implantation in children with unilateral cataract and to identify visual function
      differences according cataract type. METHODS: Clinical records of 2- to 6-year
      old patients with unilateral cataract removal and primary PC-IOL implantation
      were reviewed retrospectively. Visual acuity and ocular alignment were measured.
      Sensory fusion was assessed with the Worth 4-dot test, and stereoacuity with the
      Titmus stereo test. Cataracts were classified according to cause, lens opacity
      location, age at onset, and presence of strabismus. Clinical characteristics of
      patients who obtained good visual function were identified. RESULTS: Forty-seven
      patients were included. Among 22 (46.8%) with good vision (20/40 or better), only
      6 (27.3%) achieved good binocular function (the presence of fusion and 100
      seconds of arc or better of stereoacuity). Visual acuity was better in eyes with
      good binocular function (p=0.002). No other variables were significant for
      achieving good binocular function. CONCLUSIONS: The removal of unilateral
      cataract in a visually immature child can result in a combination of good visual
      acuity and binocular function. Good binocular function is closely related to good
      visual acuity.

PMID- 18063883
TI  - The safety and efficacy of transconjunctival sutureless 23-gauge vitrectomy.
AB  - PURPOSE: To evaluate the efficacy and safety of vitreoretinal surgery using a 23
      gauge transconjunctival sutureless vitrectomy (TSV) system for various
      vitreoretinal diseases. METHODS: A retrospective, consecutive, interventional
      case series was performed for 40 eyes of 40 patients. The patients underwent
      vitreoretinal procedures using the 23-gauge TSV system, including idiopathic
      epiretinal membrane (n=7), vitreous hemorrhage (n=11), diabetic macular edema
      (n=10), macular hole (n=5), vitreomacular traction syndrome (n=5), diabetic
      tractional retinal detachment (n=1), and rhegmatogenous retinal detachment (n=1).
      Best corrected visual acuity (BCVA), intraocular pressure (IOP), and intra- and
      post-operative complications were evaluated. RESULTS: Intraoperative suture
      placement was necessary in 3 eyes (7.5%). The median BCVA improved from 20/400
      (LogMAR, 1.21+/-0.63) to 20/140 (LogMAR, 0.83+/-0.48) at 1 week (p=0.003), 20/100
      (LogMAR, 0.85+/-0.65) at 1 month (p=0.002), 20/100 (LogMAR, 0.73+/-0.6) at 3
      months (p=0.001). In 1 eye, IOP was 5 mmHg at 2 hours and 4 mmHg at 5 hours, but
      none of the eyes showed hypotony after 1 postoperative day. No serous
      postoperative complications were observed during a mean follow-up of 8.4+/-3.4
      months (range 3-13 months) CONCLUSIONS: The 23-gauge TSV system shows promise as
      an effective and safe technique for a variety of vitreoretinal procedures. It
      appears to be a less traumatic, more convenient alternative to 20-gauge
      vitrectomy in some indications.

PMID- 18063884
TI  - Efficacy of intravitreal triamcinolone acetonide for eyes with postvitrectomy
      diabetic vitreous hemorrhage.
AB  - PURPOSE: To evaluate the efficacy of intravitreal triamcinolone acetonide (IVT)
      for the management of postvitrectomy diabetic vitreous hemorrhage. METHODS: The
      authors conducted a retrospective study of patients with postvitrectomy diabetic
      vitreous hemorrhage who were administered 4 mg (0.1 cc) of triamcinolone
      acetonide ophthalmic suspension. Ocular history, adverse events, BCVA,
      intraocular pressure, external eye examination, slit-lamp biomicroscopy, fundus
      examination, B-scan ultrasonography, and fundus photography were assessed on day
      1, weeks 1, 2, and 4 and months 2 and 3. RESULTS: There were 19 eyes of 18
      consecutive patients with mean follow-up after IVT injection of 28 weeks. Of the
      19 eyes, 17 eyes (89%) experienced clearing of vitreous hemorrhage within 1 to 5
      weeks (mean, 1.7 weeks) with visible triamcinolone precipitates along with blood
      clot in the inferior aspect of fundus. Of these 17 eyes, 12 eyes (63%) maintained
      vitreous hemorrhage-free condition at last follow-up with a mean visual acuity of
      20/63 (range, 20/320 20/25), whereas 5 (29%) developed recurrent vitreous
      hemorrhage after clearing of vitreous hemorrhage. Vitreous hemorrhage was not
      cleared in 2 eyes, which required surgical procedures. CONCLUSIONS: IVT injection
      may be beneficial for clearing recurrent postvitrectomy Diabetic Vitreous
      Hemorrhage.

PMID- 18063885
TI  - Retinal angiomatous proliferation and intravitreal bevacizumab injection.
AB  - PURPOSE: To evaluate the short-term efficacy and safety of intravitreal
      bevacizumab injection (IVBI) in patients with retinal angiomatous proliferation
      (RAP). METHODS: Seven eyes of 5 patients with RAP were included in this study.
      All of the eyes evidenced stage 2 RAP lesions, except for one eye with a stage 3
      lesion. IVBI (1.25 mg/0.05 cc) were conducted at 4 or 6-week intervals. Complete
      ocular examinations, angiographic results and optical coherence tomographic
      findings before and after the IVBI were analyzed at baseline and upon the follow
      up visits. RESULTS: Seven eyes were studied in 5 patients who had undergone IVBI.
      Partial (3 eyes) or complete (4 eyes) regression of RAP was noted after IVBI in
      all of the studied eyes. Visual acuity improved in 5 of the eyes, and was stable
      in 2 of the eyes. One eye evidenced severe intraocular inflammation after IVBI
      and a subsequent development of new RAP, which was controlled with vitrectomy and
      repeat IVBI. CONCLUSIONS: This treatment was effective over 6 months, stabilizing
      or improving visual acuity and reducing angiographic leakage. These short-term
      results suggest that IVBI may constitute a promising therapeutic option,
      particularly in the early stages of RAP.

PMID- 18063887
TI  - Disc hemorrhages in patients with both normal tension glaucoma and branch retinal
      vein occlusion in different eyes.
AB  - PURPOSE: To document the clinical features of disc hemorrhage in patients with
      branch retinal vein occlusion (BRVO) and normal tension glaucoma (NTG), and to
      evaluate the relationship between BRVO and NTG with disc hemorrhages. METHODS:
      From July 2001 to May 2006, sixteen patients with both NTG and BRVO in different
      eyes were successively collected from outpatient population of Seoul National
      University Hospital in this observational case series. The frequency and location
      of disc hemorrhages, history of associated systemic diseases, and the order of
      the time of diagnosis between NTG and BRVO were studied. RESULTS: All patients
      had unilateral BRVO, and their mean age was 63.3+/-10.6 years. Disc hemorrhages
      were detected in eight patients (50%) during the mean follow-up of 26.8 months
      (range, 3-96 months). Six patients (75%) had disc hemorrhages in the non-BRVO
      eyes and two patients (25%) in BRVO eyes. Five hemorrhages (62.5%) were located
      at inferior-temporal quadrant of the optic disc. History of systemic hypertension
      was identified in 12 patients (75.0%). In 11 patients (68.8%), NTG was diagnosed
      at the same time as BRVO. CONCLUSIONS: A higher frequency of disc hemorrhages was
      identified in patients with both BRVO and NTG. Therefore, some cases of NTG,
      especially with disc hemorrhages, may share a common vascular pathophysiology
      with BRVO.

PMID- 18063886
TI  - Evaluation of a new scoring system for retinal nerve fiber layer photography
      using HRA1 in 964 eyes.
AB  - PURPOSE: To evaluate retinal nerve fiber layer (RNFL) defect by a new scoring
      system for RNFL photography using the Heidelberg Retina Angiograph 1 (HRA1).
      METHODS: This retrospective study included 128 healthy eyes and 836 primary open
      angle glaucoma eyes. The RNFL photography using HRA1 was interpreted using a new
      scoring system, and correlated with visual field indices of standard automated
      perimetry (SAP). Using the presence of RNFL defect, darkness, width, and
      location, we established the new scoring system of RNFL photos. RESULTS: The mean
      RNFL defect score I in the early, moderate, severe, and control groups were 7.3,
      9.2, 10.4, and 3.6, respectively. The mean RNFL defect score II in the early,
      moderate, severe, and control groups were 14.5, 28.5, 43.4, and 3.4,
      respectively. Correlations between the RNFL defect score II and the mean
      deviation of SAP was the strongest of the various combinations (r=-0.675,
      P<.001). CONCLUSIONS: Using a new scoring system, we propose a method for semi
      quantitative interpretation of RNFL photographs. This scoring system may be
      helpful to distinguish between normal and glaucomatous eyes, and the score is
      associated with the severity of visual field loss.

PMID- 18063888
TI  - The clinical course of consecutive esotropia after surgical correction.
AB  - PURPOSE: To investigate the clinical course in patients who underwent surgical
      correction of consecutive esotropia. METHODS: The medical records of 13 patients
      who underwent surgical correction of consecutive esotropia were reviewed
      retrospectively. The authors investigated the deviation and surgical method at
      the time of exotropia surgery. During the follow up period, the authors also
      studied incidence of amblyopia development, the effect of occlusion therapy,
      surgical methods for consecutive esotropia, and postoperative change of
      deviation. RESULTS: The average exodeviation was 27.1 prism diopter (PD).
      Bilateral lateral rectus muscle recession was performed in all patients. In all
      patients, alternate occlusion was tried from 2 weeks after development of
      consecutive esotropia. However, there was no effect on 7 patients. None of the
      patients developed amblyopia. Surgery for consecutive esotropia was performed on
      the average 15.3 months after exotropia surgery. The average esodeviation was
      21.1PD. Medial rectus muscle recession was performed in 10 patients and lateral
      rectus muscle advancement in 3 patients. The average deviation of the subject
      group immediately after surgery was 1.2PD esodeviation, 0.9PD esodeviation one
      month after surgery, 2.4PD exodeviation 6 months after surgery, and 4.7PD
      exodeviation at the last follow up, and it showed a tendency to progress to
      exodeviation as the follow up period increased. Ten patients (76.9%) showed
      deviation within 8PD at the last follow up. CONCLUSIONS: The success rate of
      surgical correction for consecutive esotropia was a favorable outcome. But,
      careful decisions of the surgical method and amount is needed because the
      conversion of exodeviation during long-term follow-up is possible.

PMID- 18063889
TI  - Protective effects of epigallocatechin gallate after UV irradiation in cultured
      human retinal pigment epithelial cells.
AB  - PURPOSE: To evaluate the protective effects of Epigallocatechin gallate (EGCG)
      against UV irradiation in cultured human retinal pigment epithelial (RPE) cells.
      METHODS: UV irradiation was produced by a UV lamp for 30 seconds with an
      irradiance of 3.3 mW/cm2. After 5 minutes and 1 hour, we administered different
      concentrations of EGCG (0, 5, 10, 15, 25, 50, 100 uM). The cell count was
      determined under a microscope using a counting chamber and the cell activity was
      evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)
      assay. RESULTS: The cell count of cultured human RPE cells after UV irradiation
      was markedly increased in the EGCG administration group, compared with the non
      administrated group. The cell activity of the cultured human RPE cells after UV
      irradiation was markedly increased in the EGCG administration group and was
      increased in a dose-dependent way as determined by the MTT assay. CONCLUSIONS:
      The administration of EGCG increased the cell count and the cell activity after
      UV irradiation in cultured human retinal pigment epithelial cells; this suggests
      that EGCG provided protection against UV damage in cultured human retinal
      pigmented epithelial cells.

PMID- 18063890
TI  - Effects of heme oxygenase-1 inducer and inhibitor on experimental autoimmune
      uveoretinitis.
AB  - PURPOSE: Experimental autoimmune uveoretinitis (EAU) is an animal model of
      posterior uveitis and heme oxygenase-1 (HO-1) is a well-known anti-oxidant
      factor. However, there is no report a protective role of HO-1 on EAU in vivo. To
      verify that HO-1 is induced in EAU by interphotoreceptor retinoid-binding protein
      (IRBP), that an HO-1 inducers ameliorates the associated inflammation, and that
      an HO-1 inhibitor exacerbates this inflammation. METHODS: Forty four Lewis rats
      were given either 40 mol/kg hemin or 40 mol/kg SnPP (tin protoporphyrin IX) by
      intraperitoneal injection and twenty two uveitis control rats were injected with
      0.5 mL of saline once daily 5-20 days after IRBP immunization inducing EAU. Three
      normal control rats were used for Western blotting and ELISA assay of HO-1. The
      clinical uveitis signs of inflammation were scored in the three groups from 0 to
      4 on alternate three days. To confirm the clinical results, histological and
      immunohistochemical stain of HO-1 were performed on the day of peak inflammation
      and Western blotting and ELISA assay of HO-1 were performed on 6th, 12th and 18th
      day after IRBP immunization. RESULTS: Hemin, an inducer of HO-1, ameliorated the
      clinical signs of EAU. In contrast, SnPP-treated rats show that the severity of
      the clinical sign were exacerbated at the peak period of the disease. These
      results are roughly compatible with histological, immunoblotting, and
      immunohistochemical evaluations and an ELISA assay of HO-1. CONCLUSIONS: We
      suggest that HO-1 plays an important protective role in EAU.

PMID- 18063891
TI  - Role of HGF/c-Met in serum-starved ARPE-19 cells.
AB  - PURPOSE: Hepatocyte growth factor (HGF) and its receptor (HGFR/c-Met) regulate
      motility, mitogenesis, and morphogenesis in a cell type-dependent fashion. We
      report the role of HGF and c-Met on stress-induced ARPE-19 human retinal pigment
      epithelial (RPE) cells in this study. METHODS: The cells were cultured either
      with or without serum. Southern and Western blot analyses were done to determine
      the expression patterns of HGF/c-Met in serum-starved ARPE-19 cells. The cell
      proliferation pattern in serum-starved condition was analyzed using MTS assay.
      Inhibition level of cell proliferation was analyzed using a neutralizing
      monoclonal antibody against c-Met (2 microg/ml). RESULTS: Abnormal cell
      proliferation and scattering of ARPE-19 cells was observed under serum
      starvation. HGF/c-Met were expressed in serum-starved ARPE-19 cells. ARPE-19 cell
      proliferation was also enhanced with recombinant HGF treatment. Neutralization
      against c-Met inhibited the proliferation of serum-deprived ARPE-19 by 64.5%
      (n=9, S.D. 5.5%). Serum starvation appears to induce epithelial-mesenchymal
      transition of ARPE-19 cells, resulting in scatter, and the expression of alpha
      smooth muscle actin (alpha-SMA), a marker for fibrosis. CONCLUSIONS: In
      conclusion, c-Met induced under non-physiologic conditions has significant
      effects on the activation of RPE cells.

PMID- 18063892
TI  - Conjunctival Inclusion Cysts in Long-standing Chronic Vernal
      Keratoconjunctivitis.
AB  - PURPOSE: To report a case of conjunctival inclusion cysts on the corneal limbus
      of a patient with chronic vernal keratoconjunctivitis during 16 months' follow
      up. METHODS: The patient was a 26 year old male without any specific history of
      surgery or trauma. Giant papillae, shield ulcers, and Horner-Trantas dots were
      detected. During the 16 month follow-up, Sodium cromoglycate eye drops and
      Prednisolone acetate 1% eye drops were given 3 times a day. During this period,
      conjunctival cysts were detected on the corneal limbus in both eyes. In spite of
      improvement of the corneal and conjunctival conditions, the conjunctival cysts
      did not seem to show any specific changes. For relief of foreign body sensation,
      excision of the conjunctival cysts and giant papillae of the left eye and
      histopathologic examination of the specimen was performed. RESULTS: On
      histopathological examination, the conjunctival cysts consisted of
      nonkeratinizing stratified epithelial cells filled with PAS-positive mucous
      substance. Inflammatory cells were not found in the vicinity. CONCLUSIONS:
      Conjunctival inclusion cysts can be seen as an atypical finding of long-standing
      vernal keratoconjunctivitis. Mechanical friction between the giant papillae and
      conjunctiva may be a factor in inducing the formation of the conjunctival cysts.

PMID- 18063893
TI  - A case of Weill-Marchesani syndrome with inversion of chromosome 15.
AB  - PURPOSE: To present a case of Weill-Marchesani syndrome with corneal endothelial
      dysfunction due to anterior dislocation of a spherophakic lens and
      corneolenticular contact. METHODS: A 17-year-old woman presented with high myopia
      and progressive visual disturbance. She was of short stature and had
      brachydactyly. Her initial Snellen best corrected visual acuity (BCVA) was 20/50
      (-sph 20.50 -cyl 3.00 Ax 180) in her right eye and 20/40 (-sph 16.00 -cyl 6.00 Ax
      30) in her left eye. Slit lamp examination revealed a dislocated spherophakic
      lens touching corenal endothelium. A microspherophakic lens, hypoplastic ciliary
      body, and elongated zonules were confirmed on rotating Scheimpflug camera
      (Pentacam) and on ultrasound biomicroscopy. Specular microscopy showed corneal
      endothealial dysfunction. Systemic evaluation was performed, and chromosomal
      study showed 46, XX, inv (15) (q13qter). The patient was diagnosed with Weill
      Marchesani syndrome. RESULTS: Due to impending corneal decompensation,
      phacoemulsification and suture fixation of the intraocular lens were performed.
      The operation and postoperative course were uneventful. Three months
      postoperatively, the visual acuity was 20/30 (OD) and 20/40 (OS) without
      correction, and BCVA was 20/20 (+sph 0.50 -cyl 2.00 Ax 160 : OD) and 20/25 (+sph
      1.50 -cyl 3.00 Ax 30 : OS). During the follow-up period, increased corneal
      endothelial counts, hexagonality, and decreased corneal thickness were achieved.
      CONCLUSIONS: In Weill-Marchesani syndrome with a chromosomal anomaly, a
      dislocated spherophakic lens may cause severe corneal endothelial dysfunction due
      to corneolenticular contact, and prompt lensectomy is important to prevent such
      complications.

PMID- 18063894
TI  - Cancer-associated nummular loss of the retinal pigment epithelium.
AB  - PURPOSE: To report a case of cancer-associated nummular loss of the retinal
      pigment epithelium. METHODS: A 47-year-old man with a history of hepatocellular
      carcinoma presented with three weeks of bilateral visual loss. His best-corrected
      visual acuity was 20/40 in each eye. He had multiple round confluent grayish
      brown patches at the level of retinal pigment epithelium, and no pigmented
      choroidal lesions. Fluorescein angiography showed circular areas of transmission
      defect and indocyanine green angiography showed early hyperfluorescence,
      corresponding with the multiple round confluent patches. CONCLUSIONS: We report a
      case of visual paraneoplastic syndrome which showed nummular loss of the pigment
      epithelial cells which distinguishes the clinical component of BDUMP syndrome.

PMID- 18063895
TI  - [Why do health inequalities matter?].
AB  - OBJECTIVES: The aim of this study was to introduce the concept of health
      inequalities, and to discuss the underlying assumptions and ethical backgrounds
      associated with the issue, as well as the theoretical and practical implications
      of health inequalities. METHODS: Based on a review of the literature, we
      summarize the concepts of health inequalities and inequities and discuss the
      underlying assumptions and ethical backgrounds associated with these issues from
      the view of social justice theory. We then discuss the theoretical and practical
      implications of health inequalities. RESULTS: Health inequality involves ethical
      considerations, such as judgments on fairness, and it could provide a sensitive
      barometer to reflect the fairness of social arrangements. Discussion on health
      inequalities could deepen our understanding of the social etiology of health and
      provide a basis for the development of comprehensive and integrative social
      policies. CONCLUSIONS: Health equity is not a social goal in and of itself, but
      should be considered as a part of a broader effort to seek social justice.

PMID- 18063896
TI  - [Historical advances in health inequality research].
AB  - The socioeconomic inequalities in health have recently become an important public
      health concern in South Korea, and the issue has gained increasing attention from
      many South Korean researchers due to the increasing income inequality and
      widening social polarization following its economic crisis in the late 1990s.
      However, despite the mounting literature on health inequalities published in
      recent years, the history of research on health inequality in South Korea is
      premature in comparison to the long histories in several Western countries.
      Understanding the historical background underlying the issue of health inequality
      research may aid in establishing and accumulating scientifically solid evidence
      in South Korea. It may also direct the South Korean research community to develop
      research agendas that are more politically and academically appropriate for South
      Korean society. This paper describes the historical development of health
      inequality research in the West and introduces several important issues
      contributing to the advancement of health inequality research. Specifically, the
      major studies conducted before and after the UK Black Report are presented. In
      addition, the history and current status of health inequality research in South
      Korea are documented and evaluated. Finally, several research agendas for the
      quantitative and qualitative improvement of health inequality research in South
      Korea are proposed.

PMID- 18063897
TI  - [Health inequalities in Korea: current conditions and implications].
AB  - OBJECTIVES: The aim of this study is to summarize the current conditions and
      implications of health inequalities in South Korea. METHODS: Through a literature
      review of empirical studies and supplementary analysis of the data presented in
      the 1998, 2001, and 2005 KNHANEs, we evaluated the extent and trends of
      socioeconomic inequalities in both health risk factors, such as smoking, physical
      activity, and obesity, and outcomes, such as total mortality, subjective poor
      health status by self-reports and metabolic syndrome. Relative risks and odds
      ratios were used to measure differences across socioeconomic groups, and the
      relative index of inequality was used to evaluate the changes in inequalities
      over time. RESULTS: We found clear inequalities to various degrees in most health
      indicators. While little change was observed in mortality differences over time,
      the socioeconomic gaps in risk factors and morbidity have been widening, with
      much larger differences among the younger population. CONCLUSIONS: Socioeconomic
      inequalities are pervasive across various health indicators, and some of them are
      increasing. The trends in socioeconomic inequalities in health should be
      carefully monitored, and comprehensive measures to alleviate health inequalities
      are needed, especially for young populations.

PMID- 18063898
TI  - [Introduction of health impact assessment and healthy cities as a tool for
      tackling health inequality].
AB  - In order to reduce the health inequalities within a society changes need to be
      made in broad health determinants and their distribution in the population. It
      has been expected that the Health impact assessment(HIA) and Healthy Cities can
      provide opportunities and useful means for changing social policy and environment
      related with the broad health determinants in developed countries. HIA is any
      combination of procedures or methods by which a proposed 4P(policy, plan,
      program, project) may be judged as to the effects it may have on the health of a
      population. Healthy city is one that is continually creating and improving those
      physical and social environments and expanding those community resources which
      enable people to mutually support each other in performing all the functions of
      life and in developing to their maximum potential. In Korea, social and academic
      interest regarding the HIA and Healthy Cities has been growing recently but the
      need of HIA and Healthy Cities in the perspective of reducing health inequality
      was not introduced adequately. So we reviewed the basic concepts and methods of
      the HIA and Healthy Cities, and its possible contribution to reducing health
      inequalities. We concluded that though the concepts and methods of the HIA and
      Healthy Cities are relatively new and still in need of improvement, they will be
      useful in approaching the issue of health inequality in Korea.

PMID- 18063899
TI  - [The proposal of policies aimed at tackling health inequalities in Korea].
AB  - Although the New National Health Promotion Plan 2010 target to reduce health
      inequalities, whether the program will be effective for reducing the health
      inequalities in Korea remains quite unclear. More and more developed countries
      have been started to concentrate on comprehensive policies for reducing health
      inequalities. The health policies of the UK, Netherlands, and Sweden are the most
      wellknown. I propose that a comprehensive blueprint for tackling health
      inequalities in Korea should be made and that it must contain five domains: a
      target, structure and process, life-course approach, area-based approach, and
      reorganization of health care resources. The target should be based on
      determinants of health and more attention should be paid to socioeconmic factors.
      The structure and process require changes from the national health care policy
      based on medical services to the national health policy that involves the
      establishment of a Social Deputy Prime Minister and the strengthening
      multidisciplinary action. A life-course approach especially focused on the early
      childhood years. Area-based approach such as the establishment of healthy
      communities, healthy schools, or healthy work-places which are focused on
      deprived areas or places is also required. Finally, health care resources should
      be a greater investment on public resources and strengthening primary care to
      reduce health inequalities. The policy or intervention studies for tackling
      health inequalities should be implemented much more in Korea. In addition, it is
      essential to have political will to encourage policy action.

PMID- 18063900
TI  - [The association between sleep and obesity in Korean adults].
AB  - OBJECTIVES: Obesity is currently an epidemic in Korea, and sleep duration is
      thought to be one of the risk factors for obesity. The objective of this study
      was to test the hypothesis that short sleep duration is associated with obesity
      in Korean adults. METHODS: The data from the 2001 Korean National Health and
      Nutrition Survey were used, and 6,174 subjects aged 18 approximately 80 years
      were included in the analysis. Sleep duration was measured using information
      obtained from self-reported questionnaires. Obesity, the main outcome variable,
      was measured according to body mass index. Multiple regression modeling was used
      to adjust for potential confounding variables. RESULTS: The study results
      revealed a negative association between sleep duration and body mass index among
      Korean adults. These associations persisted after controlling for the potential
      confounding variables. CONCLUSIONS: These findings support the hypothesis that
      sleep duration is associated with obesity in Korean adults. In addition, these
      observations support earlier experimental sleep studies and provide a basis for
      future studies on weight control intervention by increasing the amount of sleep.

PMID- 18063901
TI  - [Determinants of sterilization among married couples in Korea].
AB  - OBJECTIVES: The purpose of this study was to examine the determinants of
      sterilization in South Korea. METHODS: This study was based on the data from the
      Korea National Fertility Survey carried out in the year 2000 by the Korea
      Institute of Health and Social Affairs. The subjects of the analysis were 4,604
      women and their husbands who were in their first marriage, in the age group of 15
      49 years. The data were analyzed by multiple logistic regression analysis.
      RESULTS: Consistent with the findings of previous studies, the woman's age and
      the number of total children increased the likelihood of sterilization. In
      addition, the year of marriage had a strong positive association with
      sterilization. Interestingly, the number of surviving sons tended to increase the
      likelihood of sterilization, whereas the woman's education level and age at the
      time of marriage showed a negative association with sterilization. Religion,
      place of residence, son preference, and the husband's education level, age and
      type of occupation were not significant determinants of sterilization.
      CONCLUSIONS: The sex of previous children and lower level of education are
      distinct determinants of sterilization among women in South Korea. More studies
      are needed in order to determine the associations between sterilization rate and
      decreased fertility.

PMID- 18063902
TI  - [Cigarette smoking and gastric cancer risk in a community-based cohort study in
      Korea].
AB  - OBJECTIVES: Gastric cancer is the most common incident cancer in Korea. Although
      Helicobacter pylori infection is the most important risk factor for the
      development of gastric cancer, cigarette smoking has also been suggested to play
      an important role in the development of gastric cancer. The objective of this
      study is to evaluate the relationship between cigarette smoking and gastric
      cancer risk in a Korean population. METHODS: The study population consisted of
      13,785 subjects who had been enrolled in the Korean Multi-Center Cancer Cohort
      between 1993 and 2002. As of December 2002, 139 incident gastric cancer cases
      were ascertained through the Korea Central Cancer Registry and the National Death
      Certificate Database. Relative risks (RR) and 95% confidence intervals (CI) for
      gastric cancer were estimated using Cox's proportional hazard model adjusted for
      age, education, alcohol drinking status and history of gastritis or ulcer.
      RESULTS: Significant dose-response relationships were observed between the
      duration of smoking and the risk of gastric cancer among the male subjects in
      comparison to non-smokers: men who smoked for 20-39 years had a 2.09- fold (95%
      CI 1.00-4.38) increase, and those who smoked for more than 40 years had a 3.13
      fold (95% CI 1.59-6.17) increase in the risk of gastric cancer (P trend<0.01).
      CONCLUSIONS: This study suggests that a longer duration of cigarette smoking may
      increase the risk of gastric cancer development in a dose-response manner in
      Korean men. The association between smoking and gastric cancer risk in women
      should be verified in future studies with a larger number of cases.

PMID- 18063903
TI  - [A review on socioeconomic position indicators in health inequality research].
AB  - OBJECTIVES: Socioeconomic position (SEP) refers to the socioeconomic factors that
      influence which position an individual or group of people will hold within the
      structure of a society. In this study, we provide a comprehensive review of
      various indicators of SEP, including education level, occupation-based SEP,
      income and wealth, area SEP, life-course SEP, and SEP indicators for women,
      elderly and youth. METHODS AND RESULTS: This report provides a brief theoretical
      background and discusses the measurement, interpretation issues, advantages and
      limitations associated with the use of each SEP indicator. We also describe some
      problems that arise when selecting SEP indicators and highlight the indicators
      that appear to be appropriate for health inequality research. Some practical
      information for use in health inequality research in South Korea is also
      presented. CONCLUSIONS: Investigation into the associations between various SEP
      indicators and health outcomes can provide a more complete understanding of
      mechanisms between SEP and health. The relationship between specific SEP
      indicators and specific health outcomes can vary by country due to the
      differences in the historical, socioeconomic, and cultural contexts of the SEP
      indicators.

PMID- 18063904
TI  - [Physician factors associated with the blood pressure control among hypertensive
      patients].
AB  - OBJECTIVES: Little is known about the physician-related factors that are
      associated with the management of hypertension. The purpose of this study was to
      determine the physician-related factors associated with blood pressure control in
      hypertensive patients. METHODS: We surveyed 154 physicians at 117 public health
      (subhealth) centers in Gyeonggi-do. Forty-one physicians completed the survey
      (response rates: 26.6%) and 31 physicians were finally included as the study
      subjects. Using the information obtained from the self-reported survey, we
      measured the physician-related factors associated with hypertension control,
      including their perception of hypertension, prescription patterns (combination
      prescription rates, specific antihypertensives prescription rates among patients
      with diabetes mellitus), and sociodemographic factors. We then collected data on
      blood pressure and medication use in patients seen by these physicians from the
      health center's information system. We compared the physicians' perceived
      hypertension control rates with the actual rates, and then evaluated the rate of
      high overestimation (overestimation by more than 25% of the median degree of
      hypertension control rate overestimation) among the physicians. The physicians'
      antihypertensive prescription patterns were also evaluated. Multiple logistic
      regression analysis was used to evaluate the independent association between
      hypertension control and physician-related factors. RESULTS: The physicians
      tended to overestimate the proportion of their patients with controlled blood
      pressure (79.5% perceived vs. 57.8% actual). The percentage of physicians with
      high overestimation was 35.5% (11 physicians). The physicians with lower control
      rates were more likely to highly overestimate their patients' control rates.
      Physicians with below-median actual control rates tended to prescribe fewer
      combination treatments for patients with uncontrolled blood pressure and
      angiotensin-converting enzyme inhibitors or fewer angiotensin receptor blockers
      for patients with diabetes mellitus. The rate of high overestimation by
      physicians was 1.31 times higher in patients with uncontrolled blood pressure
      than in patients with other conditions (OR=1.31, 95% CI: 1.17-1.48). CONCLUSIONS:
      Physicians have a tendency to overestimate the rates of hypertension control in
      their patients. Because physicians have a direct role in treatment outcomes,
      physicians' overestimation about hypertension management contributes to
      inadequate blood pressure control. Thus, interventions for improving physician'
      awareness regarding the management of patients with hypertension are needed.

PMID- 18063905
TI  - [Strengthening causal inference in studies using non-experimental data: an
      application of propensity score and instrumental variable methods].
AB  - OBJECTIVES: This study attempts to show how studies using non-experimental data
      can strengthen causal inferences by applying propensity score and instrumental
      variable methods based on the counterfactual framework. For illustrative
      purposes, we examine the effect of having private health insurance on the
      probability of experiencing at least one hospital admission in the previous year.
      METHODS: Using data from the 4th wave of the Korea Labor and Income Panel Study,
      we compared the results obtained using propensity score and instrumental variable
      methods with those from conventional logistic and linear regression models,
      respectively. RESULTS: While conventional multiple regression analyses fail to
      identify the effect, the results estimated using propensity score and
      instrumental variable methods suggest that having private health insurance has
      positive and statistically significant effects on hospital admission.
      CONCLUSIONS: This study demonstrates that propensity score and instrumental
      variable methods provide potentially useful alternatives to conventional
      regression approaches in making causal inferences using non-experimental data.

PMID- 18063906
TI  - [Trend of socioeconomic inequality in participation in cervical cancer screening
      among Korean women].
AB  - OBJECTIVES: While cervical cancer is one of the leading cancers among women
      worldwide, there are a number of effective early detection tests available.
      However, the participation rates in cervical cancer screening among Korean women
      remain low. After the nationwide efforts in 1988 and thereafter to encourage
      participation in cervical cancer screening, few studies have investigated the
      effects of socioeconomic inequality on participation in cervical cancer
      screening. The purpose of this study was to investigate 1) the level of
      socioeconomic disparities in receiving cervical cancer screening by age group and
      2) if there was an improvement in reducing these disparities between 1995 and
      2001. METHODS: Using data from the Korean National Health Status, Health Behavior
      and Belief Survey in 1995, and the Korean National Health and Nutrition
      Examination Surveys from 1998 and 2001 (sample sizes of 2,297, 3,738, and 3,283),
      age-standardized participation rates were calculated according to education
      level, equivalized household income, and job status. Odds ratios and the relative
      inequality index (RII) were also calculated after controlling for age. RESULTS:
      Women with lower education levels were less likely to attend the screening test,
      and the disparities by education level were most pronounced among women aged 60
      years and older. The RIIs among women 60 years and older were 3.64, 4.46, and
      8.64 in 1995, 1998, and 2001, respectively. Higher rates of participation were
      reported among those in the highest income category, which was more notable among
      the middle aged women (40s and 50s). An inconsistent trend in the rate of
      participation in cervical cancer screening by occupational level was found.
      CONCLUSIONS: Indicators of socioeconomic position seem to have varying impacts on
      the inequalities in the rates of participation in cervical cancer screening
      according to age group. These results demonstrate the need for more aggressive
      and age-based interventions and policy programs to eliminate the remaining
      inequalities.

PMID- 18063907
TI  - Epigenetic aberrations in malignant gliomas: an open door leading to better
      understanding and treatment.
AB  - Malignant gliomas and specially glioblastoma multiforme are the most frequent and
      devastating brain tumors in adults. Intensive molecular and cytogenetical studies
      have revealed a wide variety of deregulated genes implicated in cell cycles, DNA
      repair, apoptosis, cell migration, invasion and angiogenesis with little
      translational success. An increasing number of reports investigating epigenetic
      injuries in malignant gliomas have been recently published, although the panorama
      of CpG island aberrant hypermethylation, histone modification and chromatin
      states in these lethal tumors is only partially devised. In the present analysis,
      we discuss the magnitude and significance of epigenetic lesions in the
      pathogenesis and mechanisms of progression of malignant gliomas as well as their
      influence on patient survival. The new venue of epigenetic research provides
      tools for the identification of genes differentially methylated that may be
      implicated in tumorigenesis and furthermore, epigenetics-based drugs may
      constitute a promising alternative resource of therapy for this, to the moment,
      incurable malignancy.

PMID- 18063908
TI  - COPD. You've gone too far, baby.

PMID- 18063909
TI  - FDA sets regulations on supplement manufacturing.

PMID- 18063910
TI  - Ultrasound treatment of uterine fibroids provides long-term relief.

PMID- 18063911
TI  - Obesity spreads through social ties.

PMID- 18063913
TI  - Mayo Clinic office visit. KEEPS Trial.

PMID- 18063912
TI  - Tumor biomarkers. Hidden clues to cancer.

PMID- 18063914
TI  - Finding forgiveness. A path to better well-being.

PMID- 18063915
TI  - One on one. Do diet and exercise have an effect on breast cancer survival?

PMID- 18063916
TI  - One on one. Is bottled water better than tap water?

PMID- 18063917
TI  - Vasculitis in systemic lupus erythematosus (SLE)--assessment of peripheral blood
      mononuclear cell activation and the degree of endothelial dysfunction: initial
      report.
AB  - BACKGROUND: Inflammatory-immune changes in the vascular endothelium are one of
      the main factors initiating vessel wall damage. Enhanced expression of
      endothelial adhesion molecules and their receptors on the surface of circulating
      leukocytes seems to play an important role in the pathogenesis of vasculitis.
      Increasing evidence indicates endothelial cell activation/damage in SLE. In
      patients with SLE complicated by vasculitis, enhanced expression of integrin
      activation markers on the surface of peripheral blood mononuclear cells (PBMCs)
      has been reported. It seems relevant to assess the mechanisms of inflammatory
      response involving PBMCs and endothelial cells at particular stages of SLE
      microangiopathy. AIM: The main aim was to assess the surface expressions of the
      integrin adhesion molecules VLA-4 (CD49d) and LFA-1 (CD11a) on PBMCs as well as
      the number of circulating endothelial cells (CECs) in patients with SLE and
      complications related to inflammatory microangiopathy and to determine whether
      these parameters vary depending on disease activity. PATIENTS: Twenty-nine women
      with SLE (mean age: 38.72+/-10.23 years) were divided into subgroup I: those with
      severe disease activity according to the modified disease activity index SLEDAI,
      characterized by the presence of inflammatory microangiopathy-related
      complications such as systemic central nervous system affection and/or vasculitis
      and/or nephritis (15 women, mean age: 38.33+/-11.02 years), and subgroup II:
      patients with mild or moderate disease activity according to SLEDAI and without
      vascular complications (14 women, mean age: 39.14+/-9.72 years). METHODS:
      Expressions of VLA-4 and LFA-1 on the surface of peripheral blood lymphocytes and
      monocytes were assessed by flow cytometry using monoclonal antibodies. CECs (a
      marker of endothelial damage) were isolated from peripheral blood with anti
      CD146(S-Endo 1)-coated immunomagnetic Dynabeads. Tests for the lupus
      anticoagulant, antinuclear antibody, anti-dsDNA, and anticardiolipin antibody
      were performed in every study subject by ELISA. Erythrocyte sedimentation rate
      and serum levels of fibrinogen, C-reactive protein, the complement components C3
      and C4, urea, creatinine, and uric acid were determined by standard methods.
      Peripheral blood counts and a general urinalysis were also performed. RESULTS:
      The mean CEC count was significantly higher in SLE patients than in the control
      group (15.29+/-12.10 vs. 3.08+/-1.46 cells/ml, p<0.001). CEC counts was notably
      elevated in patient subgroup II compared with the control group (9.14+/-5.16 vs.
      3.08+/-1.46 cells/ml, p<0.05) and in subgroup I compared with subgroup II
      (21.03+/-13.96 vs. 9.14+/-5.19 cell/ml, p<0.05). In patients with severe SLE
      flares, CEC count visibly correlated with disease activity assessed by SLEDAI
      score (R=0.92, p<0.001). The expressions of VLA-4 and LFA-1 on peripheral blood
      lymphocytes in both patient subgroups were significantly higher than in the
      control group (subgroup I vs. controls: 1.70+/-1.56 vs. 0.39+/-0.26%, p<0.05, and
      1.97+/-2.60 vs. 0.67+/-0.83%, p<0.05; subgroup II vs. controls: 1.71+/-1.04 vs.
      0.39+/-0.26%, p<0.001, and 3.32+/-2.48 vs. 0.67+/-0.83%, p<0.05, for VLA-4 and
      LFA-1, respectively). There was no significant difference between the two
      subgroups of patients (1.70+/-1.56 vs. 1.71+/-1.04%, p>0.05, and 1.97+/-2.60 vs.
      3.32+/-2.48%, p>0.05, respectively). Similarly, the surface expression of LFA-1
      on circulating monocytes in patients in both subgroups was notably enhanced over
      that of the control group (91.44+/-16.00 vs. 84.95+/-19.86%, p<0.05, and 90.11+/
      10.34 vs. 84.95+/-19.86%, p<0.05, in subgroups I and II respectively) and was
      comparable in both subgroups of patients (91.44+/-16.00 vs. 90.11+/-10.33%,
      p>0.05). The surface expression of VLA-4 on peripheral blood monocytes was
      considerably higher in patients with severe disease activity than in the control
      group and in patients with less active disease (77.10+/-13.56 vs. 64.90+/-19.13%,
      p<0.05, and 77.10+/-13.56 vs. 63.40+/-20.95%, p<0.05, respectively). However,
      there was no significant difference between patients with mild or moderate
      disease activity and the control group (63.40+/-20.95 vs. 64.90+/-19.13%,
      p>0.05). CONCLUSIONS: 1) The number of CECs increases in the course of SLE and
      correlates with disease activity, indicating progressive endothelial damage.2)
      The expressions of VLA-4 and LFA-1 on the surface of peripheral blood lymphocytes
      as well as that of LFA-1 on circulating monocytes are enhanced in SLE patients
      regardless of disease activity. 3) The expression of VLA-4 on the surface of
      circulating monocytes is enhanced only in patients with severe disease activity,
      characterized by the presence of complications connected with inflammatory
      microangiopathy, which may indicate that the upregulation of VLA-4 expression in
      monocytes plays a leading role in the pathogenesis of vasculitis in SLE.

PMID- 18063918
TI  - Liver X receptors (LXRs). Part I: structure, function, regulation of activity,
      and role in lipid metabolism.
AB  - Liver X receptors (LXRs) alpha and ss belong to a family of nuclear receptors
      which form heterodimers with the retinoid X receptor and, upon ligand binding,
      stimulate the expression of target genes. LXRs were initially described as orphan
      receptors and oxidized cholesterol derivatives (oxysterols) were later identified
      as their natural ligands. In addition, several synthetic LXR agonists such as
      T0901317 and GW3965 were synthesized. Oxysterols are formed in amounts
      proportional to cholesterol content in the cell and therefore the LXRs operate as
      cholesterol sensors which protect from cholesterol overload by: 1) inhibiting
      intestinal cholesterol absorption, 2) stimulating cholesterol efflux from cells
      to high-density lipoproteins through the ATP-binding cassette transporters ABCA1
      and ABCG1, 3) activating the conversion of cholesterol to bile acids in the
      liver, and (4) activating biliary cholesterol and bile acid excretion. In
      addition, LXR agonists activate de novo fatty acid synthesis by stimulating the
      expression of a lipogenic transcription factor, sterol regulatory element-binding
      protein-1c (SREBP-1c), leading to the elevation of plasma triglycerides and liver
      steatosis. Here we describe the structure and function of the LXRs, their endo-
      and exogenous agonists and antagonists, the regulation of LXR expression and
      activity, and their role in the regulation of cholesterol and lipid metabolism.
      In the accompanying article we characterize other effects of LXRs, alterations in
      LXR expression, and changes in the level of their endogenous agonists in
      pathological conditions as well as therapeutic implications.

PMID- 18063919
TI  - Liver X receptors (LXRs). Part II: non-lipid effects, role in pathology, and
      therapeutic implications.
AB  - Liver X receptors (LXRs) alpha and ss belong to a group of nuclear receptors
      which, after ligand binding, regulate gene transcription. Their natural agonists
      are oxidized cholesterol derivatives (oxysterols). The main function of LX
      receptors is the regulation of cholesterol metabolism. In the first part of this
      work we discussed the structure and mechanism of action of LXRs, their agonists
      and antagonists, the regulation of LXR expression, and their role in cholesterol
      and lipid metabolism. In the present article we describe other roles of LXRs.
      Agonists of these receptors increase insulin sensitivity and stimulate insulin
      secretion. Activation of LXRs inhibits inflammation and autoimmune reactions.
      Moreover, pharmacological studies and genetic manipulations indicate that these
      receptors inhibit atherogenesis. LX receptors are also involved in the regulation
      of renin secretion, inhibit the formation of amyloid ss in the central nervous
      system, regulate gonadal function and steroidogenesis both in gonads and in
      adrenals, influence the proliferation and differentiation of keratinocytes, and
      inhibit the proliferation of tumor cells. Changes in the expression of these
      receptors and in the level of their agonists are observed in many diseases.
      Taking into account the multiple roles of LX receptors, their agonists may be
      applied in the future in the treatment of many disorders, including diabetes,
      inflammatory diseases, atherosclerosis, Alzheimer's disease, and hypogonadism.
      However, possible side effects should be taken into account, including
      enhancement of lipogenesis, hypertriglyceridemia, and liver steatosis. The
      function of LX receptors is also modulated by many currently used drugs such as
      statins, fibrates, and thazolidinedione derivatives.

PMID- 18063920
TI  - [Glycophorins of human erythrocytes as receptors for the malaria parasite
      Plasmodium falciparum].
AB  - Malaria causes an estimated 300-500 million clinical cases in sub-Saharan Africa
      and Indochina. The most severe form of malaria is caused by Plasmodium
      falciparum, a parasite responsible for the death of 2 million children annually.
      Understanding the molecular basis of the parasite's invasion process is important
      for the development of new drugs and vaccines. Invasion of erythrocytes by the
      malaria parasite is a multistep process involving several specific interactions
      between the parasite's ligands and receptors on red blood cells. It was shown
      that glycophorins A, B, and C, sialoglycoproteins of human erythrocytes, act as
      receptors for Plasmodium falciparum ligands of the DBL family: EBA-175 and EBA
      140 antigens. The binding specificity of EBA-175 is determined by the presence of
      sialic acid residues of the O-linked oligosaccharide chain clusters of glycphorin
      A and the amino-acid sequence, which contribute to their proper conformation.
      Glycophorin B, the next in terms of amount, can take on the role of glycophorin A
      as the receptor, but the glycophorin B- and sialic acid-dependent invasion of
      erythrocytes by Plasmodium falciparum involves a different parasite ligand. The
      third, and minor, glycophorin C appears to be the receptor for the antigen BAEBL,
      a paralogue of EBA-175. The binding of BAEBL to glycophorin C is dependent on the
      sialic acid residues of the O- and N-linked oligosaccharide chains and a peptide
      as well. It seems that the correct receptor site on glycophorin C needs to be
      elucidated in detail.

PMID- 18063921
TI  - Why fish oils may not always be adequate treatments for depression or other
      inflammatory illnesses: docosahexaenoic acid, an omega-3 polyunsaturated fatty
      acid, induces a Th-1-like immune response.
AB  - BACKGROUND: We have shown that a depletion of omega3 polysaturated fatty acids
      (PUFAs) plays a role in the pathophysiology of depression, in part because omega3
      PUFAs have anti-inflammatory effects. omega3 PUFAs are frequently employed to
      treat depression. Most if not all antidepressants have negative immunoregulatory
      effects by decreasing the production of proinflammatory cytokines, such as
      interferon-gamma (IFNgamma) and/or increasing that of anti-inflammatory
      cytokines, such as interleukin10 (IL-10). AIM: The aim of the present study was
      to examine the immunoregulary effects of the omega3 PUFAs, eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA), and the omega6 PUFA, arachidonic acid (AA),
      on the production of interferon-gamma (IFNgamma), interleukin-10 (IL-10) and
      tumor necrosis factor-alpha (TNFalpha). METHODS: This study examines the ex vivo
      effects of EPA (4.5 microM, 9 microM, 18 microM and 45 microM), DHA (1.3 microM,
      3 microM, 6 microM and 13 microM) and AA (8 microM, 16 microM, 32 microM and 80
      microM) on the LPS + PHA-stimulated production of IFNgamma, IL-10 and TNFalpha,
      and on the IFNgamma/IL-10 production ratio. RESULTS: We found that EPA did not
      have any significant effects on the above cytokines. DHA significantly increased
      the IFNgamma/IL-10 production ratio, caused by a greater reduction in IL-10 than
      in IFNgamma. AA significantly decreased TNFalpha production. DISCUSSION: The
      results show that DHA induces a Th-1-like immune response and that AA has anti
      inflammatory effects by decreasing the production of TNFalpha. Thus, the immune
      effects of omega3 PUFAs are not compatible with what is expected from
      antidepressive substances. The results of the present study show that treatment
      with fish oils, containing DHA, should be avoided in the treatment of depression.
      Toward this end, highly concentrated and pure EPA seems to be indicated.

PMID- 18063922
TI  - The role of some new factors in the pathophysiology of depression and
      cardiovascular disease: overview of recent research.
AB  - Depressive disorders and cardiovascular disease are inter-connected by a whole
      range of pathophysiological mechanisms. Three biological mechanisms are
      fundamental: activation of the hypothalamus-hypohysis-adrenal axis with a
      subsequent increase in sympathetic-adrenal system activity, decrease in vagal
      tone with a decrease in heart rate variability, and alterations of thrombogenesis
      with increased platelet aggregability. Behavioural mechanisms and psycho-social
      factors are also integral to this common pathophysiology. Recently, research has
      focused mainly on studying various forms of stress, as well as changes and
      possibilities of influencing the autonomous vegetative system. Temporal aspects
      of the incidence and development of depressive episodes in relation to
      cardiovascular disease and subsequent cardiovascular morbidity and mortality are
      being studied, as well as general mortality risk factors. These findings are
      important for clinical practice. It is evident that in patients with untreated
      depressive disorder, the risk of developing cardiovascular disease is
      significantly higher than in patients suffering from a depressive disorder being
      treated with anti-depressants. From the data published so far, it may be surmised
      that depressive disorders in patients with cardiovascular disease may be reliably
      and safely treated with anti-depressants that act as inhibitors of serotonin re
      uptake.

PMID- 18063923
TI  - The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway):
      relevance for depression - and other conditions characterized by tryptophan
      depletion induced by inflammation.
AB  - Immune activation is accompanied by induction of indoleamine (2,3)-dioxygenase
      (IDO), an enzyme which degrades tryptophan, a phenomenon which plays a role in
      the pathophysiology of major depression and post-natal depression and anxiety
      states. TRYCATs - tryptophan catabolites along the IDO pathway - such as
      kynurenine, kynurenic acid, xanthurenic acid, and quinolinic acid, have multiple
      effects, e.g. apoptotic, anti- versus pro-oxidant, neurotoxic versus
      neuroprotective, and anxiolytic versus anxiogenic effects. The aim of the present
      study was to study the immune effects of the above TRYCATS. Toward this end we
      examined the effects of the above TRYCATs on the LPS + PHA-induced production of
      interferon-gamma (IFNgamma), interleukin-10 (IL-10), and tumor necrosis factor
      alpha (TNFalpha) in 18 normal volunteers. We found that the production of
      IFNgamma was significantly decreased by all 4 catabolites. Xanthurenic acid and
      quinolinic acid decreased the production of IL-10. Kynurenine, kynurenic acid,
      and xanthurenic acid, decreased the IFNgamma/IL-10 production ratio, whereas
      quinolinic acid increased this ratio. Kynurenic acid significantly reduced the
      stimulated production of TNFalpha. It is concluded that kynurenine, kynurenic
      acid, and xanthurenic acid have anti-inflammatory effects trough a reduction of
      IFNgamma, whereas quinolinic acid has pro-inflammatory effects in particular via
      significant decreases in IL-10. Following inflammation-induced IDO activation,
      some TRYCATs, i.e. kynurenine, kynurenic acid, and xanthurenic acid, exert a
      negative feedback control over IFNgamma production thus downregulating the
      initial inflammation, whereas an excess of quinolinic acid further aggravates the
      initial inflammation.

PMID- 18063924
TI  - The course of diagnosis in autistic patients: the delay between recognition of
      the first symptoms by parents and correct diagnosis.
AB  - The primary aim of the research was to find the delay between the first symptoms
      of an autistic disorder being recognized by parents and diagnosis in our centre.
      A secondary objective was to evaluate the number of contacts with professionals
      (physicians, teachers, and speech therapists) in which parents pointed out
      special manifestations seen in children and, in spite of that, the children were
      not referred to a specialist. A retrospective study assessed 204 children (59
      girls, 145 boys) in total; 126 children (39 girls, 87 boys) with childhood autism
      (CHA), 57 (17 girls, 40 boys) with atypical autism (AA), and 21 (3 girls, 18
      boys) with Asperger's syndrome (AS). The mean age at appearance of the first
      signs was 29.7 months (range 0-70, median 30+/-17.0) in N=201, and the average
      age at diagnosis was 81.5 months (range 13-276, median 69.5+/-45.2) in N=204. The
      mean delay in making a diagnosis was 51.3 months (range 0-246, median 39+/-40.9)
      in N=201. The delay in diagnosis is shortest in patients with AA (a mean period
      of 44.4 months = 3 years and 8 months), longer in CHA patients (49.5 months = 4
      years and 2 months), and longest in patients with AS (80.8 months = 6 years and 9
      months). A statistically significant difference in the period to diagnosis was
      found between CHA and AS patients (p=0.023) and between AA and AS patients
      (p=0.019). The mean number of visits to physicians and other specialists before
      referring to a specialized centre for diagnosis in N=133 was 2.4 (range 1-5,
      median 2+/-0.9). The diagnosis of autism is made late and early educational and
      behavioural interventions cannot be initiated.

PMID- 18063925
TI  - Testosterone in first-episode schizophrenia.
AB  - OBJECTIVE: Recent neuroendocrinological studies have suggested that gonadal sex
      hormones play a significant role in the pathophysiology of schizophrenia. Low
      testosterone is associated with negative symptoms in chronic schizophrenia. The
      relevance of these findings has not yet been elucidated. The aim of our
      naturalistic open study was to explore the association between symptoms, drug
      response and testosterone levels in first-episode schizophrenia to exclude the
      effects of age, chronic illness, long-term treatment and institutionalization.
      METHODS: 68 males, consecutively hospitalised for the first time with first
      episode schizophrenia were evaluated using the Positive and Negative Syndrome
      Scale (PANSS) on admission (before treatment) and at discharge. Further, plasma
      testosterone was measured. Total testosterone was assayed using chemiluminescent
      immunoanalysis (CMIA). All patients were treated openly by monotherapy;
      risperidone being the drug of first choice. Treatment response was defined as
      delta PANSS (PANSS total on admission - PANSS total at discharge /PANSS total on
      admission). RESULTS: On average the total PANSS and PANSS subscales scores
      significantly decreased during the acute treatment. In contrast to results in
      chronic schizophrenia, the mean values of testosterone were within the normal
      range (15.36 and 22.55 nmol/l respectively) both before and after acute
      treatment. The range of normal values for the method used is given as 5.76-30.43
      nmol/l for males <50 years old. On admission only 6 patients had testosterone
      values lower than 5.76 nmol/l. No significant correlation between negative
      symptoms (negative PANSS subscale) at the beginning or at the end of acute
      treatment or between treatment response and testosterone plasma levels was found.
      CONCLUSIONS: During the first psychotic breakdown no significant association was
      observed either between total testosterone plasma levels and symptoms or
      treatment reactivity. However, schizophrenia is a heterogeneous disease. In some
      patients with first-episode schizophrenia an alteration of psychoendocrinology
      parameters has been observed. These patients may be more vulnerable to
      development of enduring negative symptoms, and pharmacotherapy based on
      neuroendocrinology profile should be considered.

PMID- 18063926
TI  - Solar activity, revolutions and cultural prime in the history of mankind.
AB  - BACKGROUND: Russian astronomer A.L. Tchijevsky published in the twenties of 20th
      century a study comparing the approximately 11-year cycling of "sunspot activity"
      and "historical process", analyzed globally since the 5th century B.C. to the
      19th century A.D. According to him, phenomena of societal "excitation", as
      revolutions, occurred synchronously with the solar maxima, and, oppositely, those
      of peaceful activities of masses, as science and arts, with the solar minima.
      Recently, Slovak philosopher E. Pales describes periodic fluctuation of
      historical events in mutually distant geographic areas during more than three
      millennia. The period lengths, however, are longer, one of the most pronounced
      being around 500 years. THE QUESTION was therefore posed: does a similar
      correlation with sunspot activity, as found for 11-year cycles, exist also in the
      500-year cycling? MATERIAL AND METHODS: The historical data consisted of two time
      series concerning revolutions in Europe and China, and of eight time series from
      activities in science and arts registered from five geographic areas. For the
      comparison, parallel time series of sunspot (Wolf) numbers, available since IInd
      century B.C., were constructed. Using periodic regression function, the times of
      peaking were estimated for each data set. RESULTS: In agreement with Tchijevsky's
      hypothesis, revolutions culminated near to solar maxima while cultural
      flourishing usually distinctly near to solar minima. This conclusion is based on
      the level of statistical significance alpha=0.05. CONCLUSION: Solar impact on
      geomagnetic field could be one of elucidating mechanisms. Recently,
      electromagnetic influencing of brain function has been realized artificially.

PMID- 18063927
TI  - Serum adiponectin concentrations and their relationship with plasma lipids in
      obese diabetic and non-diabetic Caucasians.
AB  - OBJECTIVES: Adiponectin is a novel plasma protein produced exclusively in
      adipocytes. Despite early data, its relationship with obesity and diabetes has
      been recently questioned. Since plasma lipids influence diabetes and obesity, of
      concern is whether any associations between plasma lipids and adiponectin exist.
      DESIGN AND METHODS: The aim of this study was to measure adiponectin levels and
      to investigate their associations with plasma cholesterol fractions and
      triglycerides in 73 obese non-diabetic subjects (44 women and 29 men), and 43
      obese diabetic subjects (28 women and 15 men), aged 52.7+/-11.2 and 53.1+/-11
      years, respectively, and matched for age, sex and BMI. The WHO definitions of
      obesity and diabetes were used. Adiponectin was determined by an enzyme-linked
      immunosorbent assay. RESULTS: No correlations between adiponectin and total and
      LDL cholesterol levels were shown (for the whole cohort: r=0.0130; p=0.8899, and
      r=0.0807; p=0.3958, respectively). A positive correlation between HDL cholesterol
      levels and adiponectin occured predominantly in obese women without diabetes
      (r=0.4531; p=0.0023), resulting in an overall statistical trend in the whole
      cohort (r=0.2243; p=0.0164). A negative correlation between serum adiponectin and
      triglycerides was found (r=-0.3413; p=0.0002). CONCLUSION: Adiponectin correlated
      only with TG and partially with HDL but not with LDL and total cholesterol in the
      study group of obese diabetic and obese non diabetic subjects. In view of these
      results we suggest that the role of adiponectin in human metabolism is unclear
      and merits further investigation.

PMID- 18063928
TI  - Normalization of the increased translocation of endotoxin from gram negative
      enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue
      syndrome.
AB  - There is now evidence that chronic fatigue syndrome (CFS) is accompanied by an
      increased translocation of endotoxins from gram-negative enterobacteria through
      the gut wall, as demonstrated by increased prevalences and median values for
      serum IgM and IgA against the endotoxins of gram-negative enterobacteria. This
      condition can also be described as increased gut permeability or leaky gut and
      indicates intestinal mucosal dysfunction (IMD). Here we report a case of a 13
      year old girl with CFS who showed very high values for serum IgM against the LPS
      of some enterobacteria and signs of oxidative and nitrosative stress, activation
      of the inflammatory response system, and IgG3 subclass deficiency. Upon treatment
      with specific antioxidants and a "leaky gut diet", which both aim to treat
      increased gut permeability, and immunoglobins intravenously, the increased
      translocation of the LPS of gram negative enterobacteria normalized and this
      normalization was accompanied by a complete remission of the CFS symptoms.

PMID- 18063930
TI  - Melatonin and tryptophan as therapeutic agents against the impairment of the
      sleep-wake cycle and immunosenescence due to aging in Streptopelia risoria.
AB  - All organisms present circadian rhythm in most of their physiological functions,
      and among them there stand out sleep, motor activity, immune function, the
      secretion of melatonin, and the production and release of numerous
      neurotransmitters, in particular of serotonin because of its relationship with
      the aforementioned factors. Aging changes these rhythms, altering sleep quality
      and contributing to immunosenescence. Treatment with exogenously administered
      melatonin or tryptophan may restore these impaired functions due to aging. In our
      animal model (Streptopelia risoria), both the hormone and the amino acid acted on
      the activity-rest rhythms, modulating the circulating levels of melatonin and
      serotonin, and increased the cell viability and resistance to induced oxidative
      stress of blood heterophils, at the same time as enhancing the phagocytic
      function and neutralizing the superoxide anions deriving from this immune
      function. Also, in the old individuals, the treatments with melatonin and
      tryptophan at the concentrations and times of administration considered suitable
      improved nocturnal rest besides reverting the immunosuppressory and oxidative
      effects accompanying phagocytosis at these advanced ages.

PMID- 18063929
TI  - Mid-aortic syndrome with renovascular hypertension and multisystem involvement in
      a girl with familiar neurofibromatosis von Recklinghausen type 1.
AB  - OBJECTIVES: Neurofibromatosis von Recklinghausen type 1 (NF1) is an autosomal
      dominant neurocutaneous disorder affecting one in 3 000-4 000 individuals. Mid
      aortic syndrome (MAS) is a rare condition characterized by segmental narrowing of
      abdominal aorta and stenosis of its major branches - mainly renal arteries,
      including manifestation of renovascular hypertension. MAS can be caused by
      different diseases, including NF1. MAIN FINDINGS: A 9 years old girl with primary
      diagnosis of NF1 combined with renovascular hypertension due to MAS, suffered of
      bilateral optic and chiasm glioma, pubertas praecox, speech disorder, light
      mental retardation and scoliosis. We have found a mutation in exone 34 of the NF1
      gene (17q11.2). Her father has been also diagnosed with NF1 and hypertension
      developed at early age. He has the same mutation in exone 34 of NF1 gene. The
      girl is currently treated with conservative antihypertensive medication with
      positive effect. Bilateral optic and chiasm glioma are asymptomatic at the time
      and they had been without progress over period of time. Any vascular surgery,
      neurosurgical and oncological therapy are not indicated at the present time.
      CONCLUSION: This article is a summary of clinical findings in patient with NF1
      due to NF1 gene mutation in exone 34. It confirms the importance of complex
      multidisciplinar approach to examination and taking care of NF1 patients and
      their families.

PMID- 18063931
TI  - May primary empty sella turcica be a cause of isolated ACTH deficiency? A case
      report and the review of related literature.
AB  - Isolated ACTH deficiency is an uncommon cause of secondary adrenocortical
      insufficiency and accompaniment with primary empty sella has been reported in
      several cases. We present a case of isolated ACTH deficiency associated with
      empty sella. A sixty-two year old woman was admitted to our endocrine clinic with
      complaints of weakness, fatigue, weight loss, nausea, vomiting, and lack of
      appetite for about one month. Physical examination indicated orthostatic
      hypotension and epigastric tenderness. Laboratory investigations revealed
      hypoglycemia, hyponatremia and anemia, in addition low plasma cortisole and ACTH
      levels. Serum cortisole responses to short and prolonged ACTH stimulation were
      tested and partial and accurate responses were obtained, respectively. Plasma
      ACTH and serum cortisole levels failed to respond after intravenous injection of
      human corticotropin releasing hormone. Other hypophysial hormone levels were
      within the normal reference ranges. Although cranial and abdominal computerized
      tomography images were evaluated as normal, cranial magnetic resonance imaging of
      the pituitary gland revealed 'primary empty sella turcica'. Replacement therapy
      with methylprednisolon resulted in the improvement of hypoglycemia, hyponatremia
      and clinical symptoms. Based on these results, the patient was diagnosed as
      isolated ACTH deficiency and was scheduled for follow up by our outpatient
      clinic. Our report is consistent with other reports pointing out that primary
      empty sella may be responsible for pathogenesis of isolated ACTH deficiency.

PMID- 18063932
TI  - Macroprolactinomas: retrospective follow up study in the MR imaging and
      correlation with clinical symptomatology.
AB  - OBJECTIVES: Retrospective follow-up study on patients suffering from
      macroprolactinomas which were treated with agonists of D2 receptors; the MRI
      results were correlated with the clinical symptomatology and with the level of
      prolactin in the blood. METHODS: From 1996 to 2006 we followed 38 patients
      diagnosed with macroprolactinoma. All patients underwent MRI in same protocol two
      times. The indication for MRI was based on the clinical symptomatology (signs of
      hormonal dysfunction, visual fields impairment) or increased blood level of
      prolactin. RESULTS: The first predominant clinical signs in males were local
      manifestations of expansive process and in women hormonal dysfunction.
      Intratumorous haemorrhage in patients undergoing the treatment with the agonists
      of D2 receptors is common, it was encountered in 25 cases, but only in two cases
      it was followed by a more serious clinical symptomatology, which had to be
      referred to the department of the neurosurgery. Even when there were pronounced
      regressions or near complete disappearance of the tumour and normalisation of the
      blood level of prolactin, withdrawal of the treatment with agonists of D2
      receptors caused increase in size of the adenoma and increase of level of
      prolactinaemia. CONCLUSION: Only two patients presented with serious clinical
      symptomatology associated with intratumoral hemorrhage. The hemorrhages are more
      common during the first weeks of therapy, but can happen at any time thought out
      the treatment with D2 receptor agonists. Our hypothesis: the prolactinomas with
      higher level of prolactin have greater tendency for larger hemorrhages.

PMID- 18063933
TI  - Lanreotide autogel and insulin sensitivity markers: report of 5 acromegalic
      patients and literature review.
AB  - OBJECTIVE: To evaluate the short-term effects of Lanreotide Autogel on insulin
      sensitivity markers among acromegalic patients with pituitary tumors. DESIGN:
      Prospective clinical trial with six months of follow-up. SETTING: A tertiary
      endocrinology clinic. MATERIALS AND METHODS: Naive patients (patient No. 1 and
      patient No. 3) and patients who experienced prior somatostatin analogue treatment
      (patient No. 2, patient No. 4, and patient No. 5) were included. Before and after
      6 months of Lanreotide Autogel therapy, insulin sensitivity in each subject was
      determined using homeostasis model assessment of insulin resistance and beta-cell
      function formula. Euglycemic hyperinsulinemic clamp test was also performed to
      evaluate whole insulin sensitivity and was indicated as an 'M' index. RESULTS:
      All patients experienced reduction in their HOMA-beta. We noted major HOMA-beta
      decreases accompanied by pronounced increases in M indices for patients Nos. 1, 2
      and 3 (1.03 vs. 8.22, 2.98 vs. 4.70, and 5.09 vs. 13.09, respectively). The
      increases in M indices of these patients were with marked decreases in GH levels
      (34.20 vs. 15.30 microg/l, 4.25 vs. 0.74 and 5.0 vs. 0.66 ng/mL, respectively).
      Minor decline in HOMA-beta and worsened M index and almost stable GH were
      observed in patients Nos. 4 and 5. Except for patient No. 3, all participants
      showed declining HOMA-IR. CONCLUSIONS: Short-term Lanreotide Autogel treatment
      has been observed to improve M indices of acromegalic patients whose GH levels
      exhibited marked reduction. This amelioration seemed to be related to decreases
      in GH levels rather than to a direct drug effect.

PMID- 18063934
TI  - Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in
      chronic fatigue syndrome (CFS) and major depression: evidence that an IgM
      mediated immune response against Pi is one factor underpinning the comorbidity
      between both CFS and depression.
AB  - Major depression and chronic fatigue syndrome (CFS) are accompanied by signs of
      oxidative and nitrosative stress (O&NS) and an inflammatory response.
      Phosphatidyl inositol (Pi) is thought to play a role in depression. The aim of
      the present study is to examine whether depression and CFS are characterized by
      an IgM-mediated immune response directed against Pi. Toward this end, this study
      examines the serum IgM antibodies directed against Pi in 14 patients with major
      depression, 14 patients with CFS, 14 subjects with partial CFS, and in 11 normal
      controls. We found that the prevalence and mean value for the serum IgM levels
      directed against Pi were significantly greater in patients with major depression
      and CFS than in normal controls and patients with partial CFS. There were
      significant and positive correlations between serum IgM levels directed against
      Pi and two symptoms of the FibroFatigue Scale, i.e. fatigue and depression. The
      results show that an IgM-related immune response directed against Pi may occur in
      both depression and CFS and may play a role in the pathophysiology of the key
      symptom of CFS and major depression. It is suggested that the above disorders in
      Pi result from increased O&NS in both depression and CFS. Autoanti-Pi antibodies
      may have biological effects, for example, by changing inositol 1,4,5-triphosphate
      (IP3), phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol and
      phosphatidylinositol-3,4,5-triphosphate (PIP3) production, thus interfering with
      intracellular signalling processes. Future research in major depression and CFS
      should focus on the functional consequences of the immune responses directed
      against Pi.

PMID- 18063935
TI  - Histone deacetylase inhibitor valproic acid inhibits proliferation and induces
      apoptosis in KM3 cells via downregulating VEGF receptor.
AB  - The expression of vascular endothelial growth factor receptor 1(VEGFR-1) in human
      multiple myeloma KM3 cells in vitro, effects of valproic acid (VPA), as a histone
      deacetylase inhibitor, on cell proliferation and apoptosis and the underlying
      molecular mechanism were investigated. The effects of VPA on the growth of KM3
      cells were studied by MTT assay. The apoptosis rate was determined with flow
      cytometry. The mRNA level of VEGFR was determined by RT-PCR; and
      immunocytochemistry was used to detect the protein level of ac-H4 and VEGFR. VPA
      inhibited proliferation of KM3 cells in a time- and dose-dependent manner.
      Treatment with VPA (4, 2, 1 and 0.5 mmol/L) for 48h, the apoptosis rates of KM3
      cells were (13.27+/-3.54)%, (22.13+/-1.20)%, (24.41+/-2.23)% and(40.62+/-4.28)%
      respectively. The expression of VEGFR-1 in KM3 cells were decreased in VPA
      treated group by the immunochemistry and RT-PCR, whereas the acetylated histone
      H4(ac-H4) accumulated. It suggested VPA could decrease the expression of VEGFR-1
      in KM3 cells, and it might play an important role in regulating the proliferation
      and apoptosis of multiple myeloma cell line KM3 cells. These results provide the
      framework for clinical trials.

PMID- 18063936
TI  - Genetic loading on human loving styles.
AB  - OBJECTIVES: It has been hypothesized that cerebral neurotransmitters such as
      dopamine and serotonin could play a role in human romantic bonding. However, no
      data on the genetic basis of human romantic love are currently available. To
      address this issue, we looked for associations between markers in
      neurotransmitter genes (the serotonin transporter gene, 5-HTT; the serotonin
      receptor 2A, 5HT2A; the dopamine D2 receptor gene, DRD2; and the dopamine D4
      receptor gene, DRD4) and the six styles of love as conceptualized by Lee (Eros,
      Ludus, Storge, Pragma, Mania and Agape). DESIGN: A total of 350 healthy young
      adults (165 males and 185 females, mean age: 24.1+/-3.9 years, range 18-32 years)
      filled the 24-item Love Attitudes Scale (LAS) and were genotyped for the
      following six polymorphic markers: the serotonin transporter-linked polymorphic
      region (5-HTTLPR), the 5HT2A T102C and C516T polymorphisms, the DRD2 TaqI A and
      TaqI B variants, and the DRD4 exon 3 VNTR polymorphism. RESULTS: Statistical
      analysis revealed a significant association between the DRD2 TaqI A genotypes and
      "Eros" (a loving style characterized by a tendency to develop intense emotional
      experiences based on the physical attraction to the partner), as well as between
      the C516T 5HT2A polymorphism and "Mania" (a possessive and dependent romantic
      attachment, characterized by self-defeating emotions). These associations were
      present in both sexes and remained significant even after adjustment for
      potential confounders. CONCLUSIONS: Our data provide the first evidence of a
      possible genetic loading on human loving styles.

PMID- 18063937
TI  - Effects of the atypical antipsychotic clozapine on insulin release in vitro.
AB  - OBJECTIVES: Treatment with the atypical antipsychotic clozapine is frequently
      associated with metabolic side-effects such as weight gain, lipid abnormalities
      and diabetes mellitus. Since insulin is a hormone that is involved in both the
      regulation of body weight, as well as in lipid metabolism and glucose regulation,
      an effect of clozapine on insulin secretion and/or on insulin action - at least
      in part - might explain its capability to induce these side-effects. The aim of
      this study was therefore to examine the influence of clozapine on insulin release
      in vitro. METHODS: The effect of clozapine in three different concentrations, 10(
      6), 10(-5) and 10(-4) M, was investigated on both basal (i.e. 3.3 mM glucose) and
      glucose-stimulated (i.e. 16.7 mM glucose) insulin release, using isolated rat
      islets of Langerhans. RESULTS: The presence of clozapine in the concentrations of
      10(-6), 10(-5) and 10(4 )M significantly increased basal insulin release compared
      to the control after 4 h (but not after 1 h) of incubation. As regards the
      glucose-stimulated insulin release, the presence of clozapine in the
      concentrations of 10(-5) and 10(-4) M, but not in that of 10(-6) M, significantly
      inhibited the glucose-stimulated insulin release compared to the control after
      both 1 and 4 h of incubation. CONCLUSION: This study demonstrates that the
      atypical antipsychotic clozapine exerts dual effects on insulin release in vitro,
      through stimulating basal insulin release and inhibiting glucose-stimulated
      insulin release. Both these effects of clozapine on insulin release may
      contribute to its disadvantage inducing metabolic side-effects.

PMID- 18063938
TI  - Early postnatal changes in superior mesenteric artery blood flow velocity in
      healthy term infants.
AB  - OBJECTIVES: After birth, the newborn intestinal circulation undergoes
      physiological changes. The purpose of this work was to characterize the changes
      in mesenteric blood flow velocity occuring during the first three days of life in
      healthy term infants. METHODS: 30 healthy term newborns were studied repeatedly
      at the age of 2, 24 and 70 hours. Blood flow velocity in superior mesenteric
      artery (SMA) was measured by Doppler ultrasound, peak systolic velocity (PSV),
      end-diastolic velocity (EDV) and time-averaged mean velocity (TAV) were recorded
      at each time point. Resistance index (RI) and pulsatility index (PI) were
      calculated. RESULTS: SMA EDV increased from 2 h [-5.2+/-6.8 cm/s (mean +/- SD)]
      to 24 h (12.9+/-3.8 cm/s, p<0.001) with further insignificant increase to 70 h
      (14.9+/-4.7 cm/s). At 2 h of age the mean EDV was negative in 23 of 30 cases
      (76.7%). PSV did not change between 2 h (58.0+/-21.8 cm/s) and 24 h (58.5+/-15.0
      cm/s) but it increased to 70 h (79.6+/-17.7 cm/s). TAV showed a significant
      increase with time. RI decreased from 2 h (1.09+/-0.11) to 24 h (0.78+/-0.06,
      p<0.001) with further insignificant increase to 70 h (0.81+/-0.06). CONCLUSIONS:
      The blood flow velocity in SMA increases during the early neonatal period in term
      infants. The most remarkable changes occur within the first 24 hours of life. At
      2 h of age a reversed blood flow is present in majority of infants.

PMID- 18063939
TI  - Diurnal behavioral and endocrine effects of chronic shaker stress in mice.
AB  - Experiments were performed in C57BL/6J male mice to determine 1) light/dark
      effects of acute and chronic shaker stress on open field behavioral patterns and
      2) light/dark effects of chronic stress on plasma corticosterone and oxytocin.
      Shaker stress was applied acutely (15 min) or chronically (3 or 7 days). Mice
      were tested in the open field in the light or dark phase of the circadian cycle.
      For the endocrine study, mice were exposed to 3 days of intermittent shaker
      stress and sacrificed after the last stress event (09:00 or 19:00 h). Acute or
      chronic shaker stress had no significant effects on intensity of motor activity
      and rearing of mice tested under either light condition. Mice tested in the dark
      phase had higher motor activity and exhibited lower anxiety-like behavior as
      expressed by central zone activities and had higher emotionality as expressed by
      increased defecation. Chronic stress increased corticosterone with a greater
      absolute increase in the dark period. However, the percentage stress-induced
      increase was not different between the day and night periods. The oxytocin
      response to stress was observed only during the light phase with no change seen
      at dark phase. These results show that there is a marked difference in the
      light/dark pituitary stress response with no alteration in stress induced
      behavioral changes. They also suggest that there are circadian interactions in
      the endocrine stress axis that are without consequences for open field behavior.

PMID- 18063940
TI  - Dissociation, epileptic-like activity and lateralized electrodermal dysfunction
      in patients with schizophrenia and depression.
AB  - OBJECTIVES: Recent evidence indicates frequent EEG abnormalities in dissociated
      patients. This evidence is in agreement with findings that in certain psychiatric
      patients, psychosensory symptoms of epileptogenic nature, the so-called complex
      partial seizure-like symptoms occur. With respect to these findings, a hypothesis
      examined in this study states that increased level of experienced traumatic
      stress and dissociation in pathological conditions such as schizophrenia or
      depression relates to increased score of complex partial seizure-like symptoms.
      Also is suggested that the complex partial seizure-like symptoms might be related
      to unilateral hemispheric electrophysiological dysfunction, stress and
      dissociation. PARTICIPANTS AND METHODS: Psychometric assessment of dissociation,
      stress and measurement of right-left asymmetry of bilateral EDA in patients with
      schizophrenia (N=34) and depression (N=41) in comparison to healthy controls
      (N=36). RESULTS: Results indicate that increased traumatic stress and
      dissociation in both groups of patients significantly relate to increased level
      of complex partial seizure-like symptoms, and may cause the right-left EDA
      asymmetry. CONCLUSIONS: The data suggest relationship between left-hemispheric
      asymmetry and sympathetic over-activation in schizophrenia, and between right
      hemispheric asymmetry with sympathetic under-activation in depression.

PMID- 18063942
TI  - Diagnostic imaging approach to gastro-entero-pancreatic carcinomas of
      neuroendocrine origin - single NET center experience in Poland.
AB  - AIM: The aim of the study was to review the current diagnostic approach, based on
      the experience of one center performed during a 4-year period, according to WHO
      criteria of GEP - NET. MATERIAL AND METHODS: The study group comprised case
      records of 134 patients with confirmed GEP-NET carcinomas (WHO groups 2-4). All
      patients were subjected to clinical, biochemical and imaging examinations
      performed as routine clinical work-up. The imaging techniques consisted of
      anatomical (CT, EUS) and functional approaches (SRS, mIBG and FDG PET). RESULTS:
      The clinical classification considered the primary origin of the tumor as
      follows: 49% - foregut tumors, 44% - midgut, and 7% of tumors of unknown origin.
      Group of patients with WHO 2 consisted of 98 (73%) subjects. Considering those
      with foregut tumors EUS followed by CT and SRS were used in each case. SRS and CT
      imaging was used to assess the extent of the tumor. Patients with midgut tumors
      had CT and SRS as routine diagnostic imaging examinations. Considering the above
      mentioned patients, CT and SRS were used to localize the primary tumor, and
      assess tumor extent. Overall sensitivity of CT considering the active disease
      amounted to 96%, while specificity - 75%. Sensitivity of SRS was 97%, while
      specificity- 85%. WHO 3-29 patients, 17 foregut and 9 midgut tumors, and 3 of
      unknown origin. Diagnostic imaging examinations consisted of CT. Standard SRS
      (sst2) was negative in most cases. The aggressive behaviour of this type of
      tumors was detected by means of FDG-PET. Sensitivity of CT amounted to 100%, and
      that of SRS - 44%. Specificity of CT amounted to 67% and that of SRS - 100%. WHO
      4-7 patients, including 4 foregut and 3 midgut neoplasms. The imaging approach
      consisted of CT/MR and in 5 cases FDG-PET. Sensitivity of CT amounted to 100%.
      Only one patient presented with a SRS positive study. FDG-PET sensitivity
      amounted to 100%. CONCLUSION: Diagnostic imaging of GEP-NET, consider anatomical
      and functional techniques, which should be read together. The diagnostic value of
      CT and SRS were similar in case of WHO 2, while in case of WHO 3 CT had a higher
      diagnostic accuracy. FDG-PET seems to be a very attractive imaging functional
      modality in case of patients with WHO 3 and WHO 4.

PMID- 18063941
TI  - Differences in the effect of second-generation antipsychotics on prolactinaemia:
      six weeks open-label trial in female in-patients.
AB  - OBJECTIVES: The main objective was to evaluate the effect of five second
      generation antipsychotics (amisulpride, quetiapine, olanzapine, risperidone, and
      zotepine) on prolactinaemia during 6 week therapy in 433 female in-patients with
      mainly schizophrenic disorders. Secondary objectives included identification of
      dynamics of change in serum prolactin levels and correlations of changes of
      prolactinaemia with some demographic and clinical parameters. METHODS: The trial
      was a prospective, open-label, single-center one with a flexible dosing of SGAs.
      The therapeutic effect of SGAs was assessed by a change of scores of CGI-S and
      CGI-I scales from a baseline to the endpoint. Blood samples were taken in the
      morning under fasting condition. RESULTS: Amisulpride and risperidone increased
      prolactinaemia significantly in 100% of patients, as early as after week 1 of the
      therapy. Quetiapine and zotepine relatively reduced prolactinaemia significantly,
      as early as from week 1 of the quetiapine treatment. Olanzapine led to a
      transient mild prolactin elevation. The much lower prevalence of
      hyperprolactinaemia over 2 000 mIU/l differentiates olanzapine from amisulpride
      and risperidone. Prolactin elevation did not correlate with age, menopausal
      condition, therapeutic efficacy, antipsychotic daily dose, serum levels of lipids
      and glucose. There was significant correlation with first vs. subsequent
      psychotic episodes, weight, EPS and serum levels of thyroid hormones. CONCLUSION:
      Amisulpride and risperidone had marked and early prolactin elevating effects,
      requiring, therefore, more frequent monitoring of prolactinaemia and associated
      undesirable effects and risks than olanzapine, quetiapine and zotepine.

PMID- 18063943
TI  - Depressed patients perception of the efficacy of electroconvulsive therapy and
      venlafaxine therapy.
AB  - BACKGROUND: The aim of our study was to evaluate the efficacy of
      electroconvulsive (ECT) and venlafaxine therapy from the patient's point of view.
      METHODS: We used a retrospective chart review from 22 inpatients who underwent
      ECT and 22 patients treated with venlafaxine due to resistant unipolar or bipolar
      depression. We used bilateral ECT in a median of 8 (IQR 7-9.7) sessions and
      venlafaxine therapy with a median daily dosage of 225 mg (IQR 150-225 mg) for a
      median of 4 (IQR 4-5) weeks. The main outcome was change in a self-evaluation
      scale - Short Form of the Beck Depression Inventory (BDI-SF). The response was
      defined as the decreasing of the BDI-SF score by >or=50%, remission as decreasing
      of BDI-SF score <or=4. RESULTS: We did not find significant differences between
      sex, age and BDI-SF before therapy in both groups. The reduction of BDI-SF score
      was significantly higher in the ECT group than in venlafaxine group (p=0.025).
      Significantly more patients treated with ECT reached response than patients
      treated with venlafaxine (68% vs. 23%; <0.01). The remission rate after ECT was
      not significantly higher than venlafaxine therapy (27% vs. 5%; p=0.094). The
      number needed to treat (NNT) of ECT for BDI-SF response was 3 (CI95% 1.4 to 5.2)
      and NNT for BDI-SF remission was 5 (CI95% 2.3 to 45.8). DISCUSSION: After the
      median of 3 failed antidepressant trials, ECT was more effective than venlafaxine
      in the short term therapy in some parametres according to our patients. We
      suggest that the fact that mental state was evaluated by patients themselves is
      an important pro-argument in the discussion about ECT.

PMID- 18063944
TI  - Consciousness and co-consciousness, binding problem and schizophrenia.
AB  - At this time is thought that binding of synchronized and distributed activity is
      crucial for the mechanism of consciousness. There are suggestive findings that
      disturbances in this feature binding produce disintegration of consciousness in
      schizophrenia. It leads to disturbances in reflection of the self and dissociated
      psychic fragments may be experienced as parts of the external world. Disturbances
      in the feature binding that lead to disintegration in neural communication among
      some parts of the brain thus seem to be a neurophysiological counterpart of
      psychological dissociative processes related to stress response and cognitive,
      affective and neuroendocrine dysregulation.

PMID- 18063945
TI  - Comparison of potential markers of the biological age of healthy male adults and
      paraplegics.
AB  - The actual level of the true aging of an organism is characterized by its
      biological age. By the means of measuring the function ability of its
      physiological systems, it is possible to evaluate the biological age and use it
      as an indicator of premature aging. Inclusion of the biological age screening
      among the basic health precautions should offer yet another viewpoint on how to
      objectively measure the changes in an organism corresponding to aging. The
      article presents a comparison of age dependency of selected biomarkers between
      groups of healthy men and paraplegics. The measurement of the battery of
      biomarkers was run in a group of 25 healthy male adults between 36 and 54 years
      of age. The second group was formed by 20 paraplegics - men between 33 and 50
      years of age. In spite of small size of the groups, significant differences were
      found in 4 of 6 biomarkers.

PMID- 18063946
TI  - Circadian pattern of prolactin secretion in children with growth hormone
      deficiency and congenital organic lesions in the hypothalamic-pituitary region.
AB  - OBJECTIVES: Prolactin (Prl) secretion in children manifests circadian rhythm. The
      aim of the study was to assess circadian Prl pattern in children with growth
      hormone deficiency (GHD) and congenital organic disorders in the hypothalamic
      pituitary region (HPR). MATERIAL AND METHODS: The analysis comprised 47 children
      (aged: 11.05+/-3.5 years) with GHD, divided (based on MRI) into subgroups: NORM
      (no disturbances in HPR); HP (pituitary hypoplasia) and PSIS (pituitary stalk
      interruption syndrome). The profile of circadian Prl secretion was determined,
      based on Prl measurements in serum every 3 hours during 24 hours. The macroscopic
      analysis of circadian Prl rhythm in particular groups was performed. The
      comparison group consists of 41 children (aged: 11.45+/-3.20 years) with
      idiopathic short stature (ISS). RESULTS: In GHD-HP, diurnal and nocturnal Prl
      concentrations were low but with the dispersion between them and with normal
      rhythm in most of cases. In GHD-PSIS, diurnal and nocturnal Prl concentrations
      were on the same level and the rhythm was not observed in most of cases. No
      significant differences were found in Prl secretions and Prl rhythm between GHD
      NORM and ISS. The rhythm of Prl secretion was disturbed in: 72.7% of children
      with GHD-PSIS, 23.5% - with GHD-HP, 10.5% with GHD-NORM and 7.3% with ISS, only.
      CONCLUSIONS: Congenital organic lesions of HPR are associated with quantitative
      disorders and changes of the circadian pattern of Prl secretion. In children with
      GHD without organic lesions of HPR, the circadian rhythm of Prl secretion was not
      different from that with ISS.

PMID- 18063947
TI  - Anti-vimentin antibodies and neuron-specific enolase in children with
      neurofibromatosis type-1.
AB  - OBJECTIVES: The aim of the study was to investigate the relationship of serum
      levels of neuron-specific enolase, anti-vimentin IgG, and anti-vimentin IgM
      antibodies in patients with neurofibromatosis type 1 and associated tumors (optic
      glioma, and plexiform neurofibroma). METHODS: Measurement of neuron-specific
      enolase and anti-vimentin antibodies were performed in 131 children and
      adolescents (67 males, mean age 10 years, range 4-19 years; 64 females, mean age
      11 years, range 1-20 years) with three different forms of neurofibromatosis type
      1 and in control group of 40 individuals (20 males, mean age 9 years, range 1-19
      years and 20 females, mean age 12 years, range 3-18 years). RESULTS: Anti
      vimentin IgG, IgM antibodies and NSE showed similar ability to distinguish
      between neurofibromatosis type 1 and tumors associated with neurofibromatosis
      type 1. (AUC=0.57, AUC=0.52 and AUC=0.59 respectively). NSE showed better
      diagnostic efficiency (AUC=0.68) than the anti-vimentin IgG and anti-vimentin
      IgM. (AUC=0.63 and AUC=0.56 respectively). Anti-vimentin IgG and IgM antibodies
      showed higher sensitivity (87.5% and 87.2%) at the cut off value than the NSE
      (54%). On the contrary, NSE showed higher specificity at the cut off value than
      both the anti-vimentin IgG and IgM (71% vs. 22.5% and 16% respectively).
      CONCLUSIONS: Anti-vimentin IgG and IgM and neuron-specific enolase are relevant
      markers in investigation of the patients with neurofibromatosis type 1 and
      associated tumors.

PMID- 18063948
TI  - Analysis of clinical characteristics in large-scale Chinese women with polycystic
      ovary syndrome.
AB  - OBJECTIVE: To analyze the clinical and metabolic characteristics of large-scale
      Chinese women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective study.
      SETTING: Hospital-based IVF center. PATIENT(S): Patients with PCOS. METHODS: In
      the present study, one thousand and forty PCOS patients were selected from women
      who visited the Reproductive Medicine Center at Shandong Provincial Hospital
      Shandong University between January 2002 and December 2006. All the patients had
      been performed a 75 g OGTT. Clinical characteristics, serum hormonal levels,
      glucose levels, insulin levels and lipid profiles were reviewed. INTERVENTIONS:
      An oral glucose tolerance test and insulin release test were performed for each
      woman. After overnight fasting, blood samples were collected to determine fasting
      blood glucose, blood glucose and insulin (30 min, 60 min, 120 min, 180 min) after
      digesting 75 g glucose, luteotrophic hormone (LH), follicle-stimulating hormone
      (FSH), testosterone (T), prolactin (PRL), estradiol (E2), and blood lipid levels.
      MAIN OUTCOME MEASURES: Height, weight, waistline, hip circumference, F-G grade
      for hirsutism, gonadal hormone results, blood lipid level, blood glucose
      tolerance, each-moment insulin level, and family history were determined.
      RESULTS: (i) The presence of oligomenorrhea was 62.6% while amenorrhea was
      19.71%. Menstrual disorder of all the adult patients could be traced back to
      their adolescent menarche. There were 450 obesity cases of which 259 patients
      were central obesity. The incidence of acanthosis nigricans was 15.19%, 65.19%
      with obesity. (ii) Cholesterol (4.8 +/- 0.98 vs 4.61 +/- 0.86) and LDL (3.80 +/-
      6.92 vs 2.88 +/- 1.01) were both significantly higher in the obesity patients
      than the non obesity patients. (iii) 173 patients were diagnosed as diabetes
      mellitus (DM), 179 IGT, 27 IFG and 9 (IFG and IGT). Those women with plasma
      glucose values abnormality of 0, 30 min, 60 min, 120 min, 180 min were 19 cases
      0.98% (19/173), 74 cases 42.77% (74/173), 110 cases 63.58% (110/173), 42 cases
      24.28% (42/173) and 12 cases 6.94% (12/173) respectively. Ten (10/173) patients
      would have been undetected if fasting plasma glucose levels were not evaluated,
      while omission of 30 min, 60 min, 120 min, or 180 min plasma glucose levels would
      have resulted in 16 cases (16/173), 50 cases (50/173), 28 cases (28/173) and 1
      case (1/173) being missed respectively. If we took three times blood samples to
      evaluate plasma glucose levels, 39 cases (39/173) (0 min + 30 min +60 min), 102
      cases (0 min + 30 min + 120 min), 21 cases (0 min + 30 min + 180 min), 34 cases
      (0 min + 60 min + 120 min), 45 cases (0 min + 60 min + 180 min), 123 cases (0 min
      + 120 min + 180 min) would be missed. Compared AUC of plasma glucose and insulin
      in 5 times with 3 times (0 min + 30 min + 60 min), the differences were
      statistically significant. Body mass index (BMI) was positively correlated with
      HOMA-IR (r = 0.29987 (P<0.01) as well as WHR (r = 0.12441, P<0.0001).
      CONCLUSIONS: (i) The prevalence rate of obesity was higher in PCOS. The state of
      obesity had a positive relation with insulin resistance. (ii) The prevalence rate
      of lipid profiles abnormality in obesity group was higher than in non-obesity.
      (iii) OGTT was the essential examination for all the PCOS patients.

PMID- 18063949
TI  - An analysis of spontaneous behavior following acute MDMA treatment in male and
      female rats.
AB  - 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a widely abused drug that
      impairs behavioral, emotional and cognitive functions in humans and animals. The
      aim of this study was to evaluate MDMA effects on the spontaneous behavioral
      repertoire of rats with a focus on the gender differences. MDMA was given
      subcutaneously in a single dose of 2.5, 5 and 10 mg/kg and the spontaneous
      behavior of male and female rats was studied using the open field test.
      Behavioral patterns (locomotion, rearing, floor-sniffing, air-sniffing, grooming,
      immobility and stereotypy) were registered in two sessions - 30 and 60 min
      following MDMA administration; each session lasting 5 min. We found that MDMA
      totally disrupted the structure and timing of spontaneous behavioral patterns in
      both genders; no evident differences were measured between either of the
      sessions. MDMA irrespective of the dosage produced hyperlocomotion, excessive
      floor-sniffing and almost absolute suppression of grooming and immobility. A
      biphasic effect of MDMA was found in rearing. Gender differences were present
      namely in rearing and sniffing stereotypy. This study also confirms that
      behavioral experiments should focus on more behavioral elements than only on e.g.
      locomotion and that the observer-based approach still gives the most reliable
      results.

PMID- 18063950
TI  - Effective global conservation strategies.
AB  - Using data on the global distribution of mammal, bird and amphibian species,
      Grenyer et al. conclude that planning based on individual taxa does not provide
      efficient solutions for the conservation of other taxa. They also report that the
      performance of existing global conservation strategies-endemic bird areas,
      biodiversity hotspots and global 200 ecoregions-in representing those taxa is
      often no better (and in some cases worse) than random. I argue here that the
      methodology used by Grenyer et al. was not appropriate for purported globally
      comprehensive analyses. Focusing on analyses of rare species as an example, I
      demonstrate how the data actually reveal substantial cross-taxon surrogacy and
      good performance of existing global conservation strategies.

PMID- 18063955
TI  - Patching together a world view.

PMID- 18063956
TI  - Shared genomes.

PMID- 18063957
TI  - Africa's academies.

PMID- 18063961
TI  - Solar power: California's latest gold rush.

PMID- 18063960
TI  - UN talks only one part of the negotiations needed on climate.

PMID- 18063962
TI  - Model predicts structure of crystals.

PMID- 18063963
TI  - Asia plans first cancer network.

PMID- 18063964
TI  - Saudi-Italian biomedical institute gets go-ahead.

PMID- 18063966
TI  - Fund boost for German science.

PMID- 18063974
TI  - Smart networking.

PMID- 18063976
TI  - Earth monitoring: observing the ocean from within.

PMID- 18063975
TI  - Earth monitoring: the planetary panopticon.

PMID- 18063977
TI  - Earth monitoring: not enough eyes on the prize.

PMID- 18063978
TI  - Earth monitoring: the crucial measurement.

PMID- 18063979
TI  - Few women join ranks of Germany's academic elite.

PMID- 18063980
TI  - Chance to learn and teach in the developing world.

PMID- 18063983
TI  - Earth monitoring: Cinderella science.

PMID- 18063984
TI  - Earth monitoring: vigilance is not enough.

PMID- 18063991
TI  - Earth monitoring: Whole Earth comes into focus.

PMID- 18063992
TI  - Diabetes: missing links.

PMID- 18063993
TI  - Condensed-matter physics: shear madness.

PMID- 18063994
TI  - Relativity: still special.

PMID- 18063996
TI  - Microbiology: bilingual bacteria.

PMID- 18063998
TI  - Oceanography: Siberian salt in the cellar.

PMID- 18063997
TI  - Palaeoclimate: slush find.

PMID- 18063999
TI  - Obituary: Arthur Kornberg (1918-2007).

PMID- 18064000
TI  - Sustainable technology: green chemistry.

PMID- 18064001
TI  - Snowball Earth prevention by dissolved organic carbon remineralization.
AB  - The 'snowball Earth' hypothesis posits the occurrence of a sequence of
      glaciations in the Earth's history sufficiently deep that photosynthetic activity
      was essentially arrested. Because the time interval during which these events are
      believed to have occurred immediately preceded the Cambrian explosion of life,
      the issue as to whether such snowball states actually developed has important
      implications for our understanding of evolutionary biology. Here we couple an
      explicit model of the Neoproterozoic carbon cycle to a model of the physical
      climate system. We show that the drawdown of atmospheric oxygen into the ocean,
      as surface temperatures decline, operates so as to increase the rate of
      remineralization of a massive pool of dissolved organic carbon. This leads
      directly to an increase of atmospheric carbon dioxide, enhanced greenhouse
      warming of the surface of the Earth, and the prevention of a snowball state.

PMID- 18064002
TI  - Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia.
AB  - Ventricular tachyarrhythmias are the main cause of sudden death in patients after
      myocardial infarction. Here we show that transplantation of embryonic
      cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of
      ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal
      myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased
      the incidence of VT induced by in vivo pacing. eCM engraftment results in
      improved electrical coupling between the surrounding myocardium and the infarct
      region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded
      Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo.
      eCM grafts also increased conduction velocity and decreased the incidence of
      conduction block within the infarct. VT protection is critically dependent on
      expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1):
      SMs genetically engineered to express Cx43 conferred a similar protection to that
      of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the
      potential to reduce life-threatening post-infarct arrhythmias through the
      augmentation of intercellular coupling, suggesting autologous strategies for
      cardiac cell-based therapy.

PMID- 18064003
TI  - Bv8 regulates myeloid-cell-dependent tumour angiogenesis.
AB  - Bone-marrow-derived cells facilitate tumour angiogenesis, but the molecular
      mechanisms of this facilitation are incompletely understood. We have previously
      shown that the related EG-VEGF and Bv8 proteins, also known as prokineticin 1
      (Prok1) and prokineticin 2 (Prok2), promote both tissue-specific angiogenesis and
      haematopoietic cell mobilization. Unlike EG-VEGF, Bv8 is expressed in the bone
      marrow. Here we show that implantation of tumour cells in mice resulted in
      upregulation of Bv8 in CD11b+Gr1+ myeloid cells. We identified granulocyte colony
      stimulating factor as a major positive regulator of Bv8 expression. Anti-Bv8
      antibodies reduced CD11b+Gr1+ cell mobilization elicited by granulocyte colony
      stimulating factor. Adenoviral delivery of Bv8 into tumours was shown to promote
      angiogenesis. Anti-Bv8 antibodies inhibited growth of several tumours in mice and
      suppressed angiogenesis. Anti-Bv8 treatment also reduced CD11b+Gr1+ cells, both
      in peripheral blood and in tumours. The effects of anti-Bv8 antibodies were
      additive to those of anti-Vegf antibodies or cytotoxic chemotherapy. Thus, Bv8
      modulates mobilization of CD11b+Gr1+ cells from the bone marrow during tumour
      development and also promotes angiogenesis locally.

PMID- 18064004
TI  - The molecular architecture of cadherins in native epidermal desmosomes.
AB  - Desmosomes are cadherin-based adhesive intercellular junctions, which are present
      in tissues such as heart and skin. Despite considerable efforts, the molecular
      interfaces that mediate adhesion remain obscure. Here we apply cryo-electron
      tomography of vitreous sections from human epidermis to visualize the three
      dimensional molecular architecture of desmosomal cadherins at close-to-native
      conditions. The three-dimensional reconstructions show a regular array of
      densities at approximately 70 A intervals along the midline, with a curved shape
      resembling the X-ray structure of C-cadherin, a representative 'classical'
      cadherin. Model-independent three-dimensional image processing of extracted sub
      tomograms reveals the cadherin organization. After fitting the C-cadherin atomic
      structure into the averaged sub-tomograms, we see a periodic arrangement of a
      trans W-like and a cis V-like interaction corresponding to molecules from
      opposing membranes and the same cell membrane, respectively. The resulting model
      of cadherin organization explains existing two-dimensional data and yields
      insights into a possible mechanism of cadherin-based cell adhesion.

PMID- 18064005
TI  - A stability limit for the atmospheres of giant extrasolar planets.
AB  - Recent observations of the planet HD209458b indicate that it is surrounded by an
      expanded atmosphere of atomic hydrogen that is escaping hydrodynamically.
      Theoretically, it has been shown that such escape is possible at least inside an
      orbit of 0.1 au (refs 4 and 5), and also that H3+ ions play a crucial role in
      cooling the upper atmosphere. Jupiter's atmosphere is stable, so somewhere
      between 5 and 0.1 au there must be a crossover between stability and instability.
      Here we show that there is a sharp breakdown in atmospheric stability between
      0.14 and 0.16 au for a Jupiter-like planet orbiting a solar-type star. These
      results are in contrast to earlier modelling that implied much higher
      thermospheric temperatures and more significant evaporation farther from the
      star. (We use a three-dimensional, time-dependent coupled thermosphere-ionosphere
      model and properly include cooling by H3+ ions, allowing us to model globally the
      redistribution of heat and changes in molecular composition.) Between 0.2 and
      0.16 au cooling by H3+ ions balances heating by the star, but inside 0.16 au
      molecular hydrogen dissociates thermally, suppressing the formation of H3+ and
      effectively shutting down that mode of cooling.

PMID- 18064006
TI  - Cryptomare magmatism 4.35 Gyr ago recorded in lunar meteorite Kalahari 009.
AB  - The origin and evolution of the Moon remain controversial, with one of the most
      important questions for lunar evolution being the timing and duration of basaltic
      (mare) magmatism. Here we report the result of ion microprobe U-Pb dating of
      phosphates in a lunar meteorite, Kalahari 009, which is classified as a very-low
      Ti mare-basalt breccia. In situ analyses of five phosphate grains, associated
      with basaltic clasts, give an age of 4.35 +/- 0.15 billion years. These ancient
      phosphate ages are thought to represent the crystallization ages of parental
      basalt magma, making Kalahari 009 one of the oldest known mare basalts. We
      suggest that mare basalt volcanism on the Moon started as early as 4.35 Gyr ago,
      relatively soon after its formation and differentiation, and preceding the bulk
      of lunar volcanism which ensued after the late heavy bombardment around 3.8-3.9
      Gyr (refs 7 and 8). Considering the extremely low abundances of incompatible
      elements such as thorium and the rare earth elements in Kalahari 009 (ref. 9) and
      recent remote-sensing observations illustrating that the cryptomaria tend to be
      of very-low-Ti basalt type, we conclude that Kalahari 009 is our first sample of
      a very-low-Ti cryptomare from the Moon.

PMID- 18064007
TI  - Low-temperature shear modulus changes in solid 4He and connection to
      supersolidity.
AB  - Superfluidity--liquid flow without friction--is familiar in helium. The first
      evidence for 'supersolidity', its analogue in quantum solids, came from torsional
      oscillator measurements involving 4He. At temperatures below 200 mK, the
      torsional oscillator frequencies increased, suggesting that some of the solid
      decoupled from the oscillator. This behaviour has been replicated by several
      groups, but solid 4He does not respond to pressure differences, and persistent
      currents and other signatures of superflow have not been seen. Both experiments
      and theory indicate that defects are involved; these should also affect the
      solid's mechanical behaviour. Here we report a measurement of the shear modulus
      of solid 4He at low frequencies and strains. We observe large increases below 200
      mK, with the same dependence on measurement amplitude, 3He impurity concentration
      and annealing as the decoupling seen in the torsional oscillator experiments. We
      explain this unusual elastic behaviour in terms of a dislocation network that is
      pinned by 3He at the lowest temperatures but becomes mobile above 100 mK. The
      frequency changes in the torsional oscillator experiments appear to be related to
      the motion of these dislocations, perhaps by disrupting a possible supersolid
      state.

PMID- 18064008
TI  - Controlling cavity reflectivity with a single quantum dot.
AB  - Solid-state cavity quantum electrodynamics (QED) systems offer a robust and
      scalable platform for quantum optics experiments and the development of quantum
      information processing devices. In particular, systems based on photonic crystal
      nanocavities and semiconductor quantum dots have seen rapid progress. Recent
      experiments have allowed the observation of weak and strong coupling regimes of
      interaction between the photonic crystal cavity and a single quantum dot in
      photoluminescence. In the weak coupling regime, the quantum dot radiative
      lifetime is modified; in the strong coupling regime, the coupled quantum dot also
      modifies the cavity spectrum. Several proposals for scalable quantum information
      networks and quantum computation rely on direct probing of the cavity-quantum dot
      coupling, by means of resonant light scattering from strongly or weakly coupled
      quantum dots. Such experiments have recently been performed in atomic systems and
      superconducting circuit QED systems, but not in solid-state quantum dot-cavity
      QED systems. Here we present experimental evidence that this interaction can be
      probed in solid-state systems, and show that, as expected from theory, the
      quantum dot strongly modifies the cavity transmission and reflection spectra. We
      show that when the quantum dot is coupled to the cavity, photons that are
      resonant with its transition are prohibited from entering the cavity. We observe
      this effect as the quantum dot is tuned through the cavity and the coupling
      strength between them changes. At high intensity of the probe beam, we observe
      rapid saturation of the transmission dip. These measurements provide both a
      method for probing the cavity-quantum dot system and a step towards the
      realization of quantum devices based on coherent light scattering and large
      optical nonlinearities from quantum dots in photonic crystal cavities.

PMID- 18064009
TI  - Linear and nonlinear optical spectroscopy of a strongly coupled microdisk-quantum
      dot system.
AB  - Cavity quantum electrodynamics, the study of coherent quantum interactions
      between the electromagnetic field and matter inside a resonator, has received
      attention as both a test bed for ideas in quantum mechanics and a building block
      for applications in the field of quantum information processing. The canonical
      experimental system studied in the optical domain is a single alkali atom coupled
      to a high-finesse Fabry-Perot cavity. Progress made in this system has recently
      been complemented by research involving trapped ions, chip-based microtoroid
      cavities, integrated microcavity-atom-chips, nanocrystalline quantum dots coupled
      to microsphere cavities, and semiconductor quantum dots embedded in micropillars,
      photonic crystals and microdisks. The last system has been of particular interest
      owing to its relative simplicity and scalability. Here we use a fibre taper
      waveguide to perform direct optical spectroscopy of a system consisting of a
      quantum dot embedded in a microdisk. In contrast to earlier work with
      semiconductor systems, which has focused on photoluminescence measurements, we
      excite the system through the photonic (light) channel rather than the excitonic
      (matter) channel. Strong coupling, the regime of coherent quantum interactions,
      is demonstrated through observation of vacuum Rabi splitting in the transmitted
      and reflected signals from the cavity. The fibre coupling method also allows us
      to examine the system's steady-state nonlinear properties, where we see a
      saturation of the cavity-quantum dot response for less than one intracavity
      photon. The excitation of the cavity-quantum dot system through a fibre optic
      waveguide is central to applications such as high-efficiency single photon
      sources, and to more fundamental studies of the quantum character of the system.

PMID- 18064010
TI  - A crystallizing dense magma ocean at the base of the Earth's mantle.
AB  - The distribution of geochemical species in the Earth's interior is largely
      controlled by fractional melting and crystallization processes that are
      intimately linked to the thermal state and evolution of the mantle. The existence
      of patches of dense partial melt at the base of the Earth's mantle, together with
      estimates of melting temperatures for deep mantle phases and the amount of
      cooling of the underlying core required to maintain a geodynamo throughout much
      of the Earth's history, suggest that more extensive deep melting occurred in the
      past. Here we show that a stable layer of dense melt formed at the base of the
      mantle early in the Earth's history would have undergone slow fractional
      crystallization, and would be an ideal candidate for an unsampled geochemical
      reservoir hosting a variety of incompatible species (most notably the missing
      budget of heat-producing elements) for an initial basal magma ocean thickness of
      about 1,000 km. Differences in 142Nd/144Nd ratios between chondrites and
      terrestrial rocks can be explained by fractional crystallization with a decay
      timescale of the order of 1 Gyr. These combined constraints yield thermal
      evolution models in which radiogenic heat production and latent heat exchange
      prevent early cooling of the core and possibly delay the onset of the geodynamo
      to 3.4-4 Gyr ago.

PMID- 18064013
TI  - Cold shower for AIDS vaccines.

PMID- 18064011
TI  - Identification of protein pheromones that promote aggressive behaviour.
AB  - Mice use pheromones, compounds emitted and detected by members of the same
      species, as cues to regulate social behaviours such as pup suckling, aggression
      and mating. Neurons that detect pheromones are thought to reside in at least two
      separate organs within the nasal cavity: the vomeronasal organ (VNO) and the main
      olfactory epithelium (MOE). Each pheromone ligand is thought to activate a
      dedicated subset of these sensory neurons. However, the nature of the pheromone
      cues and the identity of the responding neurons that regulate specific social
      behaviours are largely unknown. Here we show, by direct activation of sensory
      neurons and analysis of behaviour, that at least two chemically distinct ligands
      are sufficient to promote male-male aggression and stimulate VNO neurons. We have
      purified and analysed one of these classes of ligand and found its specific
      aggression-promoting activity to be dependent on the presence of the protein
      component of the major urinary protein (MUP) complex, which is known to comprise
      specialized lipocalin proteins bound to small organic molecules. Using calcium
      imaging of dissociated vomeronasal neurons (VNs), we have determined that the MUP
      protein activates a sensory neuron subfamily characterized by the expression of
      the G-protein Galpha(o) subunit (also known as Gnao) and Vmn2r putative pheromone
      receptors (V2Rs). Genomic analysis indicates species-specific co-expansions of
      MUPs and V2Rs, as would be expected among pheromone-signalling components.
      Finally, we show that the aggressive behaviour induced by the MUPs occurs
      exclusively through VNO neuronal circuits. Our results substantiate the idea of
      MUP proteins as pheromone ligands that mediate male-male aggression through the
      accessory olfactory neural pathway.

PMID- 18064014
TI  - Frontiers of Clinical Investigation 2007.

PMID- 18064015
TI  - BBC apologizes for airing AIDS 'denialist' documentary.

PMID- 18064016
TI  - Spat over firing threatens medical school at US-Mexico border.

PMID- 18064017
TI  - Institutional changes may mean more resources for Indian scientists.

PMID- 18064018
TI  - Polio eradication campaign copes with unusual outbreak.

PMID- 18064019
TI  - Profile: Hugh Herr.

PMID- 18064027
TI  - Poring over pores: alpha-hemolysin and Panton-Valentine leukocidin in
      Staphylococcus aureus pneumonia.

PMID- 18064029
TI  - Sensitive cilia set up the kidney.

PMID- 18064030
TI  - Building the bionic T cell.

PMID- 18064031
TI  - Dying T cells trigger autoimmunity in HIV.

PMID- 18064032
TI  - Putting the heat on cancer.

PMID- 18064033
TI  - Incapacitating the immune system in cystic fibrosis.

PMID- 18064034
TI  - Secrets of a superbug.

PMID- 18064037
TI  - Broadly neutralizing antibodies protect against hepatitis C virus quasispecies
      challenge.
AB  - A major problem in hepatitis C virus (HCV) immunotherapy or vaccine design is the
      extreme variability of the virus. We identified human monoclonal antibodies
      (mAbs) that neutralize genetically diverse HCV isolates and protect against
      heterologous HCV quasispecies challenge in a human liver-chimeric mouse model.
      The results provide evidence that broadly neutralizing antibodies to HCV protect
      against heterologous viral infection and suggest that a prophylactic vaccine
      against HCV may be achievable.

PMID- 18064039
TI  - Granzyme B-induced cell death exerted by ex vivo CTL: discriminating requirements
      for cell death and some of its signs.
AB  - Granzyme B (gzmB) of cytotoxic T lymphocytes (CTL) is essential for recovery from
      intracellular pathogens, but the molecular basis of its action is still
      unresolved. Here, we analyzed gzmB-mediated death pathways under physiological
      conditions using ex vivo virus-immune CTLs that express perf and gzmB, but not
      gzmA (gzmB(+)CTL). We show that gzmB(+)CTL abrogate target cell proliferation
      most likely by inducing cell death, independent of caspases and mitochondrial
      signaling. In addition, the data reveal that gzmB(+)CTL independently induce pro
      apoptotic processes either via caspase-3/-7, leading to plasma membrane
      perturbance and ROS production or via Bid/Bak/Bax, resulting in cytochrome c
      release and that both pathways elicit loss of DeltaPsi(m). Our data provide
      evidence for a pleiotropic pro-apoptotic function of gzmB presumably to
      counteract evasion strategies of pathogens and to control tumors.

PMID- 18064040
TI  - Transcriptional activation of caspase-6 and -7 genes by cisplatin-induced p53 and
      its functional significance in cisplatin nephrotoxicity.
AB  - This study examined the role of cisplatin-induced p53 activation in regulation of
      caspases and cellular injury during cisplatin nephrotoxicity. The executioner
      caspase-6 and -7 but not caspase-3 were identified as transcriptional targets of
      p53 in cisplatin injury as revealed by chromatin immunoprecipitation, a reporter
      gene and electrophoretic mobility shift assays, and real-time PCR following
      overexpression and inhibition of p53. DNA binding by p53 involved the first
      introns of the human and mouse caspase-7 gene and the mouse caspase-6 gene.
      Studies in human kidney, breast, ovary, colon, and prostate tumor cell lines also
      validated these findings. Treatment of p53 (-/-) cells with cisplatin did not
      induce caspase-6 and -7 expression and subsequent activation. In caspase-3 (-/-)
      cells, inhibition of caspase-6 and -7 activations markedly prevented cisplatin
      induced cell death. In an in vivo model of cisplatin nephrotoxicity inhibition of
      p53 activation by a p53 inhibitor suppressed transactivation of the caspase-6 and
      -7 genes and prevented renal failure. p53 (-/-) mice were resistant to cisplatin
      nephrotoxicity as assessed by renal function and histology. These studies provide
      first evidence for p53-dependent transcriptional control of the caspase-6 and -7
      genes and its functional significance in cisplatin injury to renal cells and
      functional implication of cisplatin-induced p53 induction in vitro and in vivo in
      cisplatin nephrotoxicity.

PMID- 18064041
TI  - DNA damage induces two distinct modes of cell death in ovarian carcinomas.
AB  - Activation of p53 by cellular stress may lead to either cell cycle arrest or
      apoptotic cell death. Restrictions in a cell's ability to halt the cell cycle
      might, in turn, cause mitotic catastrophe, a delayed type of cell death with
      distinct morphological features. Here, we have investigated the contribution of
      p53 and caspase-2 to apoptotic cell death and mitotic catastrophe in cisplatin
      treated ovarian carcinoma cell lines. We report that both functional p53 and
      caspase-2 were required for the apoptotic response, which was preceded by
      translocation of nuclear caspase-2 to the cytoplasm. In the absence of functional
      p53, cisplatin treatment resulted in caspase-2-independent mitotic catastrophe
      followed by necrosis. In these cells, apoptotic functions could be restored by
      transient expression of wt p53. Hence, p53 appeared to act as a switch between
      apoptosis and mitotic catastrophe followed by necrosis-like lysis in this
      experimental model. Further, we show that inhibition of Chk2, and/or 14-3-3sigma
      deficiency, sensitized cells to undergo mitotic catastrophe upon treatment with
      DNA-damaging agents. However, apoptotic cell death seemed to be the final outcome
      of this process. Thus, we hypothesize that the final mode of cell death triggered
      by DNA damage in ovarian carcinoma cells is determined by the profile of proteins
      involved in the regulation of the cell cycle, such as p53- and Chk2-related
      proteins.

PMID- 18064042
TI  - Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation
      of mitochondrial hexokinase-II.
AB  - Akt activation supports survival of cardiomyocytes against ischemia/reperfusion,
      which induces cell death through opening of the mitochondrial permeability
      transition pore (PT-pore). Mitochondrial depolarization induced by treatment of
      cardiomyocytes with H(2)O(2) is prevented by activation of Akt with leukemia
      inhibitory factor (LIF). This protective effect is observed even when
      cardiomyocytes treated with LIF are permeabilized and mitochondrial
      depolarization is elicited by elevating Ca(2+). Cell fractionation studies
      demonstrate that LIF treatment increases both total and phosphorylated Akt in the
      mitochondrial fraction. Furthermore, the association of Akt with HK-II is
      increased by LIF. HK-II contains consensus sequences for phosphorylation by Akt
      and LIF treatment induces PI3K- and Akt-dependent HK-II phosphorylation. Addition
      of recombinant kinase-active Akt to isolated adult mouse heart mitochondria
      stimulates phosphorylation of HK-II and concomitantly inhibits the ability of
      Ca(2+) to induce cytochrome c release. This protection is prevented when HK-II is
      dissociated from mitochondria by incubation with glucose 6-phosphate or HK-II
      dissociating peptide. Finally LIF increases HK-II association with mitochondria
      and dissociation of HK-II from mitochondria attenuates the protective effect of
      LIF on H(2)O(2)-induced mitochondrial depolarization in cardiomyocytes. We
      conclude that Akt has a direct effect at the level of the mitochondrion, which is
      mediated via phosphorylation of HK-II and results in protection of mitochondria
      against oxidant or Ca(2+)-stimulated PT-pore opening.

PMID- 18064043
TI  - Regulating Vav1 phosphorylation by the SHP-1 tyrosine phosphatase is a fine
      tuning mechanism for the negative regulation of DISC formation and Fas-mediated
      cell death signaling.
AB  - The actin cytoskeleton association is required for caspase 8-independent Fas/CD95
      receptor internalization, a critical step for an optimal death-inducing signaling
      complex formation along the endocytic pathway, leading to efficient activation of
      the caspase cascade and, ultimately, cell death. However, the way in which this
      initiation phase of Fas receptor signaling is regulated is still unknown. We
      report herein that, in B cells, upon Fas engagement, the tyrosine phosphatase SHP
      1-regulated Vav dephosphorylation, by downmodulating the Fas-ezrin-actin linkage
      is a fine-tune switch-off mechanism that the cell uses as a way to terminate the
      receptor internalization, controlling therefore the time and extent of the DISC
      formation and cell death.

PMID- 18064038
TI  - Neurophysiological biomarkers for drug development in schizophrenia.
AB  - Schizophrenia represents a pervasive deficit in brain function, leading to
      hallucinations and delusions, social withdrawal and a decline in cognitive
      performance. As the underlying genetic and neuronal abnormalities in
      schizophrenia are largely unknown, it is challenging to measure the severity of
      its symptoms objectively, or to design and evaluate psychotherapeutic
      interventions. Recent advances in neurophysiological techniques provide new
      opportunities to measure abnormal brain functions in patients with schizophrenia
      and to compare these with drug-induced alterations. Moreover, many of these
      neurophysiological processes are phylogenetically conserved and can be modelled
      in preclinical studies, offering unique opportunities for use as translational
      biomarkers in schizophrenia drug discovery.

PMID- 18064044
TI  - The upregulation of GLAST-1 is an indirect antiapoptotic mechanism of GDNF and
      neurturin in the adult CNS.
AB  - Glial cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) protect
      retinal ganglion cells (RGCs) from axotomy-induced apoptosis. It is likely that
      neuroprotection by GDNF or NTN in the adult central nervous system (CNS) involves
      indirect mechanisms and independent signal transduction events. Extracellular
      glutamate is a trigger of apoptosis in injured RGCs, and glutamate transporter
      levels can be upregulated by GDNF. Therefore, GDNF may indirectly protect RGCs by
      enhancing glutamate uptake in the retina. We studied the upregulation of the
      glutamate transporters GLAST-1 and GLT-1 by GDNF and NTN, and the intracellular
      pathways required for GDNF/NTN neuroprotection. GDNF required phosphoinositide-3
      kinase (PI3K) and Src activity to upregulate GLAST-1 and GLT-1. NTN required PI3K
      activity to upregulate GLAST-1 and did not affect GLT-1 levels. PI3K activity was
      also important for GDNF and NTN neuroprotection following optic nerve
      transection. However, GDNF also required Src and mitogen-activated protein kinase
      activity to prevent RGC apoptosis. RNA interference demonstrated that the
      upregulation of GLAST-1 by GDNF and NTN is required to rescue RGCs. Thus,
      additional independent signal transduction events, together with the upregulation
      of GLT-1 by GDNF, differentiate the biological activity of GDNF from NTN.
      Furthermore, the upregulation of the glial glutamate transporter GLAST-1 by both
      factors is an indirect neuroprotective mechanism in the CNS.

PMID- 18064045
TI  - Insights into kinetochore-DNA interactions from the structure of Cep3Delta.
AB  - The CBF3 complex is an essential core component of the budding yeast kinetochore
      and is required for the centromeric localization of all other kinetochore
      proteins. We determined the crystal structure of a large section of the protein
      Cep3 from CBF3, which is the only component with obvious DNA-binding motifs. The
      protein adopts a roughly bilobal shape, with an extended dimerization interface.
      The dimer has a large central channel that is sufficient to accommodate duplex B
      form DNA. The zinc-finger domains emerge at the edges of the channel, and could
      bind to the DNA in a pseudo-symmetrical manner at degenerate half-sites in the
      centromeric sequence. We propose a mechanism for the modulation of DNA affinity
      by an acidic activator domain, which could be applicable to a wider family of
      transcription factors.

PMID- 18064046
TI  - Ku recruits XLF to DNA double-strand breaks.
AB  - XRCC4-like factor (XLF)--also known as Cernunnos--has recently been shown to be
      involved in non-homologous end-joining (NHEJ), which is the main pathway for the
      repair of DNA double-strand breaks (DSBs) in mammalian cells. XLF is likely to
      enhance NHEJ by stimulating XRCC4-ligase IV-mediated joining of DSBs. Here, we
      report mechanistic details of XLF recruitment to DSBs. Live cell imaging combined
      with laser micro-irradiation showed that XLF is an early responder to DSBs and
      that Ku is essential for XLF recruitment to DSBs. Biochemical analysis showed
      that Ku-XLF interaction occurs on DNA and that Ku stimulates XLF binding to DNA.
      Unexpectedly, XRCC4 is dispensable for XLF recruitment to DSBs, although
      photobleaching analysis showed that XRCC4 stabilizes the binding of XLF to DSBs.
      Our observations showed the direct involvement of XLF in the dynamic assembly of
      the NHEJ machinery and provide mechanistic insights into DSB recognition.

PMID- 18064047
TI  - Mitochondrial biogenesis: is an old dog still teaching us new tricks? Meeting on
      the Assembly of the Mitochondrial Respiratory Chain.

PMID- 18064048
TI  - Temperature-sensitive reaction intermediate of F1-ATPase.
AB  - F(1)-ATPase is a rotary molecular motor that makes 120 degrees stepping
      rotations, with each step being driven by a single-ATP hydrolysis. In this study,
      a new reaction intermediate of F(1)-ATPase was discovered at a temperature below
      4 degrees C, which makes a pause at the same angle in its rotation as when ATP
      binds. The rate constant of the intermediate reaction was strongly dependent on
      temperature with a Q(10) factor of 19, implying that the intermediate reaction
      accompanies a large conformational change. Kinetic analyses showed that the
      intermediate state does not correspond to ATP binding or hydrolysis. The addition
      of ADP to the reaction mixture did not alter the angular position of the
      intermediate state, but specifically lengthened the time constant of this state.
      Conversely, the addition of inorganic phosphate caused a pause at an angle of +80
      degrees from that of the intermediate state. These observations strongly suggest
      that the newly found reaction intermediate is an ADP-releasing step.

PMID- 18064049
TI  - Creating immune privilege: active local suppression that benefits friends, but
      protects foes.
AB  - Natural regulatory mechanisms prevent inappropriate immune activation to self and
      innocuous foreign antigens. Here, we adapt the notion of immune privilege, which
      was originally applied to transplanted tissues, to consider how antigenic tumour
      cells and chronic pathogens might exploit natural regulatory mechanisms to become
      non-immunogenic. This conceptual approach reveals new mechanistic perspectives
      that may help to explain the paradoxical persistence of tumours and chronic
      pathogens, and suggests new opportunities to improve immunotherapy to treat these
      chronic inflammatory diseases.

PMID- 18064050
TI  - Complement driven by conformational changes.
AB  - Complement in mammalian plasma recognizes pathogenic, immunogenic and apoptotic
      cell surfaces, promotes inflammatory responses and marks particles for cell
      lysis, phagocytosis and B-cell stimulation. At the heart of the complement system
      are two large proteins, complement component C3 and protease factor B. These two
      proteins are pivotal for amplification of the complement response and for
      labelling of the target particles, steps that are required for effective
      clearance of the target. Here we review the molecular mechanisms of complement
      activation, in which proteolysis and complex formation result in large
      conformational changes that underlie the key offensive step of complement
      executed by C3 and factor B. Insights into the mechanisms of complement
      amplification are crucial for understanding host defence and pathogen immune
      evasion, and for the development of complement-immune therapies.

PMID- 18064051
TI  - Fcgamma receptors as regulators of immune responses.
AB  - In addition to their role in binding antigen, antibodies can regulate immune
      responses through interacting with Fc receptors (FcRs). In recent years,
      significant progress has been made in understanding the mechanisms that regulate
      the activity of IgG antibodies in vivo. In this Review, we discuss recent studies
      addressing the multifaceted roles of FcRs for IgG (FcgammaRs) in the immune
      system and how this knowledge could be translated into novel therapeutic
      strategies to treat human autoimmune, infectious or malignant diseases.

PMID- 18064052
TI  - Metastatic prostatic adenocarcinoma to the orbit diagnosed by prostate-specific
      antigen staining.

PMID- 18064053
TI  - Homocysteine, folates, and the eye.
AB  - Plasma homocysteine has been identified as a risk factor for arterial disease,
      retinal artery and vein occlusions, and other common eye diseases. The value of
      treating an elevated plasma homocysteine with folic acid for preventing further
      vascular disease has not been proven. Although secondary prevention of coronary
      artery disease using this approach has been unsuccessful, trials on primary
      prevention of stroke and loss of cognitive function with folic acid
      supplementation appear to be successful. Further trial data are awaited. In
      patients with premature retinovascular disease, the measurement of plasma
      homocysteine is suggested and reduction of elevated homocysteine with folic acid
      for secondary prevention of retinal arterial and venous occlusion. Meanwhile, the
      debate on fortification of flour for primary prevention of neural tube defects,
      which has already taken place in North America, continues in European countries.
      Such fortification could have an impact on primary and secondary prevention of
      vascular disease.

PMID- 18064054
TI  - Intervention for intermittent distance exotropia with overcorrecting minus
      lenses.
AB  - AIM: There are numerous treatment options for intermittent distance exotropia.
      The aim of this study is to evaluate the use of overcorrecting minus lenses as a
      primary treatment option for intermittent distance exotropia (IDEX) and determine
      ocular alignment status after 5 years from commencement of the study. METHODS:
      Prospective nonrandomised longitudinal cohort study in which 21 patients were
      recruited with a diagnosis of IDEX. Treatment was instigated with the minimum
      minus lens required to achieve control of the manifest deviation. The strength of
      lenses was reduced over time while monitoring the results of orthoptic
      measurements. The results were evaluated by nonparametric (Wilcoxon) and
      parametric (paired t-test) analysis. RESULTS: Thirteen female and eight male
      patients were recruited with a mean age of 5 years at the start of treatment.
      There was a significant reduction in angle of deviation after treatment.
      Overcorrecting lenses did not appear to induce myopia. Twenty-four per cent of
      the patients had a successful outcome, 28% had a good outcome, and 33% required
      surgery at a later date. CONCLUSIONS: Fifty-two per cent of the patients achieved
      a successful or good outcome with overcorrecting minus lenses alone, and this was
      maintained for at least 1 year follow-up. Those requiring surgery had been unable
      to wean out of lenses but had a successful outcome after one procedure. We
      recommend overcorrecting minus lenses as a primary treatment option for IDEX with
      the knowledge that surgery, if subsequently required, is safely delayed to an
      older age without prior loss of binocular vision.

PMID- 18064055
TI  - Comparison of postoperative intraocular pressure in patients with Densiron-68 vs
      conventional silicone oil: a case-control study.
AB  - A solution of perfluorohexyloctane and silicone oil with a specific gravity of
      1.06 g/cm(3) (Densiron-68) has similar properties as conventional silicone oil
      (SO) in terms of the shape of the bubble and its ability to act as an internal
      tamponade agent. We conducted a case-control study to compare the postoperative
      intraocular pressure (IOP) in patients treated with Densiron-68 with those
      treated with SO. METHODS: Seventy-one eyes of 71 patients and 57 eyes of 57
      patients who had received Densiron-68 and SO, respectively, were included in our
      study. Both groups were found to have matched for their preoperative
      comorbidities (diabetes, glaucoma, phakic status, and refractive errors). IOP at
      first day, between seventh and fourteenth day, and at 4 week postoperatively was
      recorded. RESULTS: The mean IOP was higher in patients treated with Densiron-68
      at day 1 and between seventh and fourteenth day postoperatively (P=0.05 and 0.01,
      respectively). By the 4th week, the IOP difference between the two groups was
      insignificant (P=0.17). The difference in the two groups could still be
      clinically significant and the raised IOP in Densiron-68 group was more difficult
      to treat in some cases.On day 1, nine eyes (12.7%) in the Densiron-68 group and
      two eyes (3.5%) in the SO group had IOP greater than 30 mmHg. At 4 weeks, IOP of
      more than 30 mmHg was seen in nine eyes (12.7%) in the Densiron-68-treated group
      and in one eye (1.8%) in the SO group. CONCLUSION: The use of Densiron-68 was
      associated with a higher IOP in the early postoperative period when compared with
      SO.

PMID- 18064056
TI  - Intravitreous bevacizumab to treat subfoveal choroidal neovascularization in
      highly myopic eyes: short-term results.
AB  - AIM: To describe the anatomical and visual outcome of subfoveal and juxtafoveal
      choroidal neovascularization (CNV) in highly myopic eyes treated by intravitreal
      bevacizumab. METHODS: Prospective, nonrandomized, multicentric, interventional
      pilot study. Twenty-six highly myopic eyes from 25 patients with subfoveal and
      juxtafoveal CNV were treated by three monthly intravitreal injections with 1.25
      mg bevacizumab. Patients were evaluated for best-corrected visual acuity (BCVA)
      and optical coherence tomography at baseline and then monthly. Fluorescein
      angiography was performed at baseline and at month 3. RESULTS: Patients averaged
      49.5 years of age (SD 16.0, range 29-82). Five patients were male and 20 were
      female. BCVA at baseline averaged 20/62 (range 20/200-20/32) and 20/38 (range
      20/160-20/20) at month 6. Average central foveal thickness was 282.4 microm (SD
      68.3, range 168-447) at baseline and 224.0 microm (SD 46, range 132-294) at month
      6. Fifteen eyes were naive for treatment and 11 eyes had been previously treated
      by photodynamic therapy (PDT) (average 2.5 PDT sessions). Leakage from CNV had
      ceased in all eyes at month 3 and CNV was still closed at month 6. Neither ocular
      nor systemic safety issues appeared during the follow-up. CONCLUSIONS:
      Intravitreal bevacizumab seems to be an effective and safe therapeutic procedure
      to treat subfoveal and juxtafoveal CNV in highly myopic eyes. Further studies are
      required to verify the efficacy and usefulness of this therapy compared with
      established treatments for this condition.

PMID- 18064057
TI  - Surgical management of corneal perforation secondary to gonococcal
      keratoconjunctivitis.
AB  - AIMS: To report five cases of gonococcal keratoconjunctivitis with severe corneal
      involvement treated with therapeutic keratoplasty. DESIGN: Retrospective case
      series. METHODS: Five consecutive cases of gonococcal keratoconjunctivitis
      treated with keratoplasty for corneal perforation, with a mean age of 21.2 years,
      were analysed by patient's history, surgical approaches, and clinical outcomes,
      corrected visual acuity at initial visit and last follow-up. RESULTS: All adult
      cases were originally diagnosed as epidemic keratoconjunctivitis by elsewhere,
      and corneal perforation occurred with a mean duration of 11 days after
      development of conjunctivitis. While laboratory tests revealed Neisseria
      gonorrhoeae in all five cases, three patients showed resistance to ofloxacin.
      Intensive medical treatment using penicillins and/or cephems was initiated. Two
      patients had peripheral corneal perforations, one had a paracentral perforation,
      and another, a large corneal perforation with stromal melting. One case had a
      central microcorneal perforation. In all cases, the anterior chamber was flat.
      Corneal perforations were treated with lamellar or penetrating keratoplasty using
      cryopreserved or fresh corneal grafts. All grafts remained clear during the mean
      follow-up period of 34.9 months. Final best-corrected visual acuity ranged from
      20/60 to 20/16. CONCLUSIONS: Severe gonococcal keratoconjunctivitis can benefit
      from intensive surgical and medical intervention resulting in satisfactory visual
      rehabilitation.

PMID- 18064058
TI  - Morphological changes of the anterior segment after laser peripheral iridotomy in
      primary angle closure.
AB  - PURPOSE: To study changes in anterior segment morphology after laser peripheral
      iridotomy (LPI) in primary angle closure (PAC) using anterior segment optical
      coherence tomography (AS-OCT). METHODS: LPI was performed on 15 consecutive
      primary angle closure patients (15 eyes). AS-OCT was used to record the
      morphology of the anterior segment before and after LPI. The central anterior
      chamber (AC) depth, the diameter of the pupil, the lens thickness, and the AC
      volume were measured. The peripheral AC depth and the configuration of iris were
      also observed qualitatively. The intraocular pressure (IOP) was measured by
      Goldmann applanation tonometer. RESULTS: The mean central AC depth was 1.939+/
      0.228 and 1.970+/-0.235 mm before and after LPI, respectively, increasing by
      1.6%, P=0.001. In all eyes but two, the central AC depth increased. The AC volume
      changed significantly after LPI (73.86+/-14.58 vs 84.14+/-17.45 microl, P<0.001)
      and it increased in all eyes. The iris flattened and the peripheral AC deepened
      after LPI in all 15 eyes. The mean IOP was 17.8+/-3.3 and 15.9+/-3.1 mmHg before
      and after LPI, respectively, P=0.042. The changes of pupil diameter and lens
      thickness were not statistically significant. CONCLUSIONS: LPI leads not only to
      the increase of peripheral anterior chamber depth and anterior chamber volume but
      also to an increase of central anterior chamber depth in eyes with primary angle
      closure.

PMID- 18064059
TI  - Factors associated with foveoschisis and foveal detachment without macular hole
      in high myopia.
AB  - PURPOSE: To investigate the associated factors of foveoschisis and foveal
      detachment without macular hole in highly myopic eyes. METHODS: A cross-sectional
      study of 124 eyes of 68 highly myopic patients was performed. The patients
      underwent complete ocular examination, fundus photography, and optical coherence
      tomography (OCT). RESULTS: Of the 124 eyes, 10 (8%, 10/124) had foveoschisis or
      foveal detachment without a macular hole on OCT examination. On the basis of
      univariate analysis, six variables were associated with the pathologic changes,
      including age over 40 years (P=0.018), spherical equivalent over 10 D (P=0.042),
      axial length over 31 mm (P=0.001), macular chorioretinal atrophy (P=0.00003),
      posterior staphyloma (P=0.0003), and vitreoretinal interface factors, including
      epiretinal membrane, posterior vitreoschisis, and vitreomacular traction
      (P=0.00002). In the multivariate analysis, three factors were independently
      associated with foveoschisis and foveal detachment without macular hole in high
      myopia: axial length, macular chorioretinal atrophy, and vitreoretinal interface
      factors. CONCLUSIONS: Foveoschisis and foveal detachment without macular hole are
      sight-threatening disorders in highly myopic eyes. Axial length, macular
      chorioretinal atrophy, and vitreoretinal interface factors were independently
      associated with these pathological conditions. Thus, both intraocular and outer
      ocular wall factors play important roles and merit further study.

PMID- 18064060
TI  - The selective 5-HT1A receptor antagonist WAY-100635 inhibits neuronal activity of
      the ventromedial prefrontal cortex in a rodent model of Parkinson's disease.
AB  - OBJECTIVE: The ventral part of the medial prefrontal cortex (mPFC) plays an
      important role in initiation and control of voluntary movement, mood and
      cognition. However, after the degeneration of the nigrostriatal pathway, the
      neuronal activity of the ventral mPFC and the role of serotonin(1A) (5
      hydroxytryptamine, 5-HT(1A)) receptors in the firing of the neurons are still
      unknown. The present study is to investigate the change of neuronal activity in
      the ventral mPFC and the effect of systemic administration of the selective 5
      HT(1A) receptor antagonist WAY-100635 on the activity of the neurons in normal
      and 6-hydroxydopamine (6-OHDA)-lesioned rats. METHODS: Single unit responses were
      recorded extracellularly with glass microelectrodes from ventral mPFC neurons in
      normal rats and 6-OHDA unilaterally lesioned rats in vivo. RESULTS: 6-OHDA lesion
      of the substantia nigra pars compacta (SNc) significantly increased the firing
      rate with no change in the firing pattern of neurons of the ventral mPFC in rats.
      Systemic administration of WAY-100635 (0.1 mg/kg, i.v.) did not change the mean
      firing rate and firing pattern of ventral mPFC neurons in normal rats. In
      contrast, WAY-100635 significantly decreased the mean firing rate of the neurons
      in rats with 6-OHDA lesion of the SNc. CONCLUSION: These data suggest that the
      degeneration of the nigrostriatal pathway results in an increase of neuronal
      activity of ventral mPFC and dysfunction of 5-HT(1A) receptor.

PMID- 18064061
TI  - Effect of acetylcholine on pain-related electric activities in hippocampal CA1
      area of normal and morphinistic rats.
AB  - OBJECTIVE: To examine the effect of acetylcholine (ACh) on the electric
      activities of pain-excitation neurons (PEN) and pain-inhibitation neurons (PIN)
      in the hippocampal CA1 area of normal rats or morphinistic rats, and to explore
      the role of ACh in regulation of pain perception in CA1 area under normal
      condition and morphine addiction. METHODS: The trains of electric impulses
      applied to sciatic nerve were set as noxious stimulation. The discharges of PEN
      and PIN in the CA1 area were recorded extracellularly by glass microelectrode. We
      observed the influence of intracerebroventricular (i.c.v.) injection of ACh and
      atropine on the noxious stimulation-evoked activities of PEN and PIN in the CA1
      area. RESULTS: Noxious stimulation enhanced the electric activity of PEN and
      depressed that of PIN in the CA1 area of both normal and addiction rats. In
      normal rats, ACh decrease the pain-evoked discharge frequency of PEN, while
      increased the frequency of PIN. These effects reached the peak value at 4 min
      after injection of ACh. In morphinistic rats, ACh also inhibited the PEN electric
      activity and potentialized the PIN electric activity, but the maximum effect
      appeared at 6 min after administration. The ACh-induced responses were
      significantly blocked by muscarinic receptor antagonist atropine. CONCLUSION:
      Cholinergic neurons and muscarinic receptors in the hippocampal CA1 area are
      involved in the processing of nociceptive information and they may play an
      analgesia role in pain modulation. Morphine addiction attenuated the sensitivity
      of pain-related neurons to the noxious information.

PMID- 18064062
TI  - ATP depletion is the major cause of MPP+ induced dopamine neuronal death and worm
      lethality in alpha-synuclein transgenic C. elegans.
AB  - OBJECTIVE: To investigate the toxic effect of environmental neurotoxin MPP+ to C.
      elegans and identify the mechanisms that cause the toxicity. METHODS: Human alpha
      synuclein transgenic C. elegans was used as the animal model, the toxic effect of
      MPP+ to dopamine (DA) neurons and the lifespan of worms was tested. The worms
      were feed with OP50 to determine whether ATP increase can rescue the worm from
      toxicity. ATP level and aberrant protein accumulation were analyzed in the MPP+
      treated worms with or without OP50 addition. RESULTS: We found that MPP+ induced
      DA cell death and worm lethality, which could be prevented by OP50 treatment.
      OP50 exerted the protective effect by up-regulating ATP level, even though it
      also induced accumulation of alpha-synuclein. Despite the undefined role of
      protein aggregation to the cell death, our results showed that the toxicity of
      MPP+ was mainly caused by the ATP depletion in the alpha-synuclein transgenic C.
      elegans. CONCLUSION: MPP+ could induce DA neuronal death and worm lethality in
      alpha-synuclein transgenic C. elegans; Compared with the aggregation of alpha
      synuclein, the major cause of MPP+ toxicity appeared due to ATP depletion.

PMID- 18064063
TI  - Inhibiting effect of vagal nerve stimulation to seizures in epileptic process of
      rats.
AB  - OBJECTIVE: Our previous work suggested that sensitivity of hippocampal neurons is
      changed in process of epileptic activities, and closely parallel to the dynamic
      characteristic of epileptic activity of the neurons. This study investigated the
      sensitivity of epileptic brain to vagal nerve stimulation (VNS) in epileptic
      process. METHODS: Epileptic model was evoked by penicillin. Left vagal nerves
      were stimulated to inhibit the seizures induced by penicillin. The
      electrocorticography (ECoG) and electromyography (EMG) were recorded to analyze
      inhibiting effect of VNS in epileptic process. RESULTS: It was found that VNS
      could inhibit the seizures caused by penicillin, and the inhibiting effect of VNS
      to seizures increased as the vagal nerve stimulating time prolonged. It was also
      found that the inhibiting effect of VNS to seizures decreased in epileptic
      process. CONCLUSION: The results suggested that the sensitivity of epileptic
      brain to VNS was different in epileptic process. The inhibiting effect of VNS to
      seizure decreased as the development of seizures.

PMID- 18064064
TI  - No changes in densities of cannabinoid receptors in the superior temporal gyrus
      in schizophrenia.
AB  - OBJECTIVE: In recent years, abnormal changes in the endocannabinoid system have
      been found in schizophrenia. The superior temporal gyrus (STG) is strongly
      implicated in the pathophysiology of schizophrenia, particularly with regards to
      auditory hallucinations. In this study, we investigated the binding density of
      cannabinoid CB1 receptors in the STG of schizophrenia patients compared to
      control subjects. METHODS: Quantitative autoradiography was used to investigate
      the binding densities of [(3)H]SR141716A (a selective antagonist) and [(3)H]CP
      55940 (an agonist) to the CB1 receptors in the STG. Post-mortem brain tissue was
      obtained from the NSW Tissue Resource Centre (Australia). RESULTS: Contrasting to
      previous findings in the alterations of CB1 receptor densities in the prefrontal,
      anterior and posterior cingulate cortex of schizophrenia, which were suggested to
      be associated to impairment of cognition function, no significant difference was
      found between the schizophrenia and control cases in both [(3)H]SR141716A and
      [(3)H]CP-55940 binding. CONCLUSION: We suggest that CB1 receptors in the STG are
      not involved in the pathology of schizophrenia and the auditory hallucination
      symptom of this disease.

PMID- 18064065
TI  - Evoked membrane potential change in rat optic nerve fiber: computer simulation.
AB  - OBJECTIVE: The optic nerve is a key component regarding research on visual
      prosthesis. Previous pharmacological and electrical studies has pinned down the
      main features of the mechanisms underlying the nerve impulse in the rat optic
      nerve, and this work proposed a mathematical model to simulate these phenomena.
      METHODS: The main active nodal channels: fast Na+, persistent Na+, slow K+ and a
      fast repolarizing K+ (A-current) were added on a double layer representation of
      the axon. A simplified representation of K+ accumulation and clearance in the
      vicinity of the Ranvier node was integrated in this model. RESULTS: The model was
      able to generate the following features. In the presence of 4-aminopyridine (4
      AP), spike duration increased and a depolarizing afterpotential (DAP) appeared.
      In the presence of 4-AP and tetraethylammonium (TEA), the DAP was followed by a
      hyperpolarizing afterpotential (AHP) and the amplitude of this AHP increased with
      the frequency of the stimulation. In normal conditions (no drugs): DAP and AHP
      were absent after a single action potential (AP) and a short train of AP; there
      was a relative refractoriness in amplitude lasting for 30 ms after an AP; an
      early AHP was revealed by a continuous depolarizing current; and there was a
      partial spike adaptation for a long current step stimulus. CONCLUSION: The model
      successfully reproduced previous experiments results including long-lasting
      stimulation experiment, which is known to modify nerve physiological parameter
      values and is a key issue for visual prosthesis research.

PMID- 18064066
TI  - Effect of heartbeat perception on heartbeat evoked potential waves.
AB  - OBJECTIVE: Early researches found that different heartbeat perceivers have
      different heartbeat evoked potential (HEP) waves. Two tasks were considered in
      our experiments to get more details about the differences between good and poor
      heartbeat perceivers at attention and resting state. METHODS: Thirty channels of
      electroencephalogram (EEG) were recorded in 22 subjects, who had been subdivided
      into good and poor heartbeat perceivers by mental tracking task. Principal
      component analysis (PCA) was applied to remove cardiac field artifact (CFA) from
      the HEP. RESULTS: (1) The good heart-beat perceivers showed difference between
      attention and resting state in the windows from 250 ms to 450 ms after R wave at
      C3 location and from 100 ms to 300 ms after R wave at C4 location; (2) The
      difference waveforms between good and poor heartbeat perceivers was a positive
      waveform at FZ from 220 ms to 340 ms after R wave, which was more significant in
      attention state. CONCLUSION: Attention state had more effect on the HEPs of good
      heartbeat perceivers than that of poor heartbeat perceivers; and perception
      ability influenced HEPs more strongly in the attention state than in the resting
      state.

PMID- 18064067
TI  - Stem cells tropism for malignant gliomas.
AB  - Various studies have demonstrated the tremendous tropism of stem cells for
      malignant gliomas, making these cells a potential vehicle for delivery of
      therapeutic genes to disseminated glioma cells. However, little is known about
      the mechanisms underlying the glioma-induced tropism of stem cells. Soluble
      factors including chemokines or growth factors released and expressed by glioma
      cells at least mediate the tropism of stem cells for gliomas. Here we review the
      possible mechanisms of stem cells tropism for malignant gliomas.

PMID- 18064068
TI  - ATP-sensitive potassium channels: novel potential roles in Parkinson's disease.
AB  - The ATP-sensitive potassium (K(ATP)) channels which extensively distribute in
      diverse tissues (e.g. vascular smooth muscle, cardiac cells, and pancreas) are
      well-established for characteristics like vasodilatation, myocardial protection
      against ischemia, and insulin secretion. The aim of this review is to get insight
      into the novel roles of K(ATP) channels in Parkinson's disease (PD), with
      consideration of the specificities K(ATP) channels in the central nervous system
      (CNS), such as the control of neuronal excitability, action potential,
      mitochondrial function and neurotransmitter release.

PMID- 18064070
TI  - Contribution of evanescent waves to the far field: the atomic point of view.
AB  - Evanescent modes of the electromagnetic field are seldom invoked in conventional
      far-field optics, as their contribution far from the source (a few wavelengths)
      is negligible. Contradicting this fact, in recent theoretical works, based on a
      particular decomposition of the free-space Green tensor, it has been asserted
      that evanescent waves do indeed contribute to the far field, where they appear as
      an additional ~1/r component of the field. We provide an explicit demonstration
      that evanescent modes do not contribute to the power radiated to the far field by
      any dipolar source. First we derive an expression for the free-space field
      susceptibility in which contributions from evanescent and homogeneous modes are
      separated, and then we use linear response theory to compute the decay rate for
      an atomic dipole in vacuum.

PMID- 18064069
TI  - How to improve the survival of the fetal ventral mesencephalic cell transplanted
      in Parkinson's disease?
AB  - It has been extensively confirmed that fetal ventral mesencephalic cell (VMC)
      transplantation can ameliorate the symptoms of Parkinson's disease (PD). But
      there are still several problems to be resolved before the extensive clinical
      application of this technology. The major limitations are the poor survival of
      grafted dopamine (DA) neurons and restricted dopaminergic reinnervation of host
      striatum. Some attempts have been made to solve these problems including use of
      some trophic factor and co-transplantation with neural/paraneural origins. The
      purpose of this review is to overview advances of the means improving the
      survival of grafts and their current limitations.

PMID- 18064071
TI  - Crucial effects of coupling coefficients on quasi-phase-matched harmonic
      generation in an optical superlattice.
AB  - Coupling of optical parametric processes in an optical superlattice through
      quadratic nonlinearity was analyzed theoretically. Solving the coupled equations,
      we found that efficient quasi-phase-matched third-harmonic (TH) generation
      depends not only on the magnitude of the coupling coefficients but also on their
      ratio. Theoretically, all the fundamental energy can be transferred to the TH at
      a particular ratio. In other cases, there exists an optimum condition that
      corresponds to a maximum TH conversion efficiency. The result is of practical
      importance for the design of TH devices.

PMID- 18064072
TI  - Anomaly in a high-numerical-aperture diffractive focusing lens.
AB  - We show an anomalous behavior in a diffractive lens in which the spot size at the
      focus reaches a minimum at a numerical aperture of ~0.5 and then increases
      significantly at higher values. Theoretical and experimental results are
      presented, along with a comparison with refractive aplanatic lenses, in which the
      anomaly does not appear to exist.

PMID- 18064073
TI  - Single-mode operation of a coiled multimode fiber amplifier.
AB  - We report a new approach to obtaining single-transverse-mode operation of a
      multimode fiber amplifier in which the gain fiber is coiled to induce significant
      bend loss for all but the lowest-order mode. We demonstrated this method by
      constructing a coiled amplifier using Yb-doped, double-clad fiber with a core
      diameter of 25 microm and a numerical aperture of ~0.1 (V approximately 7.4) .
      When the amplifier was operated as an amplified-spontaneous-emission source, the
      output beam had an M(2) value of 1.09 +/- 0.09 ; when seeded at 1064 nm, the
      slope efficiency was similar to that of an uncoiled amplifier. This technique
      will permit scaling of pulsed fiber lasers and amplifiers to significantly higher
      pulse energies and peak powers and cw fiber sources to higher average powers
      while maintaining excellent beam quality.

PMID- 18064074
TI  - Transform-limited spectral compression due to self-phase modulation in fibers.
AB  - We demonstrate near-transform-limited pulse generation through spectral
      compression arising from nonlinear propagation of negatively chirped pulses in
      optical fiber. The output pulse intensity and phase were quantified by use of
      second-harmonic generation frequency-resolved optical gating. Spectral
      compression from 8.4 to 2.4 nm was obtained. Furthermore, the phase of the
      spectrally compressed pulse was found to be constant over the spectral and
      temporal envelopes, which is indicative of a transform-limited pulse. Good
      agreement was found between the experimental results and numerical pulse
      propagation studies.

PMID- 18064075
TI  - Holographic interferometry and the fractional Fourier transformation.
AB  - The fractional Fourier transform (FRT) is shown to be of potential use in
      analyzing the motion of a surface by use of holographic interferometry. The extra
      degree of freedom made available by the use of the FRT allows information
      regarding both translational and tilting motion to be obtained in an efficient
      manner.

PMID- 18064076
TI  - Phenanthrenequinone-doped poly(methyl methacrylate) photopolymer bulk for volume
      holographic data storage.
AB  - We present the design and fabrication of a phenanthrenequinone-doped poly(methyl
      methacrylate) photopolymer material. Large blocks of samples were made, and the
      material showed negligible shrinkage after optical exposures. We recorded and
      reconstructed 250 holograms at a single spot, using a 1-cm(3) block.

PMID- 18064077
TI  - Effects of object roughness on partially coherent image formation.
AB  - Phase perturbations in the object plane of a partially coherent imaging system
      are found to produce artifacts in the aerial image. It is demonstrated that phase
      perturbations of as little as lambda/30 rms can produce visible deformation in
      the final image for modest coherence factors, such as sigma(c) = 0.4. A
      combination of simulation and experiment is used to demonstrate the effects.
      Application to line-edge roughness in lithography is described.

PMID- 18064078
TI  - Effect of light-collection geometry on reconstruction errors in Abel inversions.
AB  - The Abel inversion, used to reconstruct axisymmetric radial profiles from line-of
      sight intensity measurements, is increasingly used to make spatially resolved
      combustion measurements. An Abel deconvolution is valid only when incoming rays
      are parallel, whereas most practical optical setups used for emission imaging
      consist of single-lens and multilens systems that collect light in a cone, over a
      nonzero solid angle. A ray-tracing simulation was performed to aid in
      understanding how optical collection geometry affects measured intensity signals
      and the resultant reconstructed emissivity profiles. Simulation results are
      compared with emission tomography measurements performed on an axisymmetric
      laminar diffusion flame.

PMID- 18064079
TI  - Interferometric microimaging based on geometrical spin-redirection phase.
AB  - A novel scheme for an interferometric microscope with which to visualize a
      geometrical spin-redirection phase image that represents the local inclination of
      microsurface structures of an object is proposed. The observed phase depends on
      the state of polarization and the optical constants of the object material, which
      enable one to distinguish the spin-redirection phase from the conventional
      dynamical-phase. A preliminary experiment was performed, and the phase images
      obtained were found to be consistent with those predicted by computer simulation
      based on a theoretical model.

PMID- 18064080
TI  - Wavelength-interrogated optical sensor for biochemical applications.
AB  - A novel miniature integrated-optical sensor for versatile multichannel
      applications is described. Wavelength-modulation techniques using laser diodes
      (vertical-cavity surface-emitting lasers) are used to interrogate multiple
      waveguide sensing regions on a single integrated-optical chip for accurate
      measurement of effective refractive-index changes at a high data rate. With the
      experimental miniature sensor system, a resolution of DN(PP) = 10(-7) (short
      term, peak to peak) of the effective refractive index was demonstrated. In terms
      of surface-mass coverage, this resolution corresponds to D?(PP) = 130 fg/mm(2).

PMID- 18064081
TI  - Lasing characteristics of a pendant drop deformed by an applied electric field.
AB  - The lasing properties of an oval-shaped resonant cavity (ORC) with a continuously
      variable aspect ratio have been studied. The ORC was formed with a dye-doped
      pendant drop placed inside a variable static electric field. When the drop ORC
      was pumped by a nitrogen laser, lasing from the ORC was found to have strong
      directional emission characteristics and an intensity enhancement factor as great
      as 19.5. Calculated results of light rays escaping from ORC's by refraction are
      in good agreement with the experimental data.

PMID- 18064082
TI  - Composite cavity semiconductor fiber ring laser.
AB  - A passive subring cavity that served as mode selector was inserted into a
      semiconductor fiber ring laser to generate a stable lasing spectrum. A narrow
      linewidth of less than 10 kHz with unidirectional operation in the composite
      cavity ring laser was achieved. Tuning over a range of 20 nm was obtained by
      application of 0-30 V dc to a piezoelectric transducer in the subring cavity.

PMID- 18064083
TI  - Widely tunable continuous-wave Raman laser in diatomic hydrogen pumped by an
      external-cavity diode laser.
AB  - What is to the authors' knowledge the first experimental demonstration of a
      nonresonant cw Raman laser pumped by a tunable external-cavity diode laser (ECDL)
      is presented. The ECDL is phase-frequency locked to a high-finesse Raman laser
      cavity containing diatomic hydrogen (H(2)) by the Pound-Drever-Hall locking
      technique. The Stokes lasing threshold occurs at a pump power of 400 +/- 30 muW,
      and a maximum photon conversion efficiency of 12.0 +/- 1.3% is achieved at 1.6 mW
      of pump power. A 40-nm tuning range of the cw Stokes emission, 1174-1214 nm, is
      obtained by tuning of the wavelength of the ECDL pump source.

PMID- 18064084
TI  - Synchronization of chaotic mode hopping.
AB  - We propose and demonstrate a scheme for generating synchronized chaotic mode
      hopping in two wavelength-tunable lasers whose tuning range covers multiple
      longitudinal modes. Chaotic mode hopping resulting in large hops in wavelength is
      induced by delayed electrical feedback. We show that, by coupling part of the
      output of one laser into another, one can synchronize the chaotic mode hopping of
      two separate lasers and obtain synchronized chaotic on-off modulation patterns in
      multiple corresponding wavelength bands.

PMID- 18064085
TI  - Interfacial shape and contact-angle measurement of transparent samples with
      confocal interference microscopy.
AB  - A model has been developed that predicts the effective optical path through a
      thick, refractive specimen on a reflective substrate, as measured with a scanning
      confocal interference microscope equipped with a high-numerical-aperture
      objective. Assuming that the effective pinhole of the confocal microscope has an
      infinitesimal diameter, only one ray in the illumination bundle (the magic ray)
      contributes to the differential optical path length (OPL). A pinhole with finite
      diameter, however, allows rays within a small angular cone centered on the magic
      ray to contribute to the OPL. The model was incorporated into an iterative
      algorithm that allows the measured phase to be corrected for refractive errors by
      use of an a priori estimate of the sample profile. The algorithm was validated
      with a reflected-light microscope equipped with a phase-shifting laser-feedback
      interferometer to measure the interface shape and the 68 degrees contact angle of
      a silicone-oil drop on a coated silicon wafer.

PMID- 18064086
TI  - Nd:YAG oscillator amplifier system with a passive ring self-pumped phase
      conjugate mirror.
AB  - A ring self-pumped phase-conjugate mirror with rhodium-doped barium titanate is
      used to correct aberrations in a laser-diode-pumped zigzag slab Nd:YAG oscillator
      amplifier system. A diffraction-limited output of 360 mJ is achieved in a 36-ns
      pulse duration at a repetition rate of 100 Hz.

PMID- 18064087
TI  - Thermo-optical effect and saturation of nonlinear absorption induced by gray
      tracking in a 532-nm-pumped KTP optical parametric oscillator.
AB  - We present experiments that show that gray tracking modifies the parametric gain
      and the generated wavelengths of a KTP optical parametric oscillator pumped at
      532 nm near degeneracy. These perturbations occur over a limited range of pump
      intensity. We propose a satisfactory model that takes into account photochromic
      damage, the thermo-optical effect, and the combined processes of creation and
      saturation of a two-photon absorber at 532 nm. The temperature dependence of
      Sellmeier equations of KTP is also established at 20-200 degrees C.

PMID- 18064088
TI  - Phase-separation dynamics of circular domain walls in the degenerate optical
      parametric oscillator.
AB  - We study the dynamics of the formation of circular domain walls, which are large
      intensity structures, in a degenerate optical parametric oscillator. We show that
      the mean-field and the propagation models predict the same increase in the domain
      size proportional to t(1/3) .

PMID- 18064090
TI  - Dynamic Franz-Keldysh effect: perturbative to nonperturbative regime.
AB  - We study theoretically the dynamic Franz-Keldysh effect for quantum wells excited
      by a cw optical field and a terahertz (THz) frequency driving field. By
      monitoring the THz sidebands one can show that for, increasing THz-field
      amplitudes, nonperturbative effects become predominant, and one must account for
      THz-field-induced nonlinearities to all orders.

PMID- 18064089
TI  - Diode-pumped singly resonant continuous-wave optical parametric oscillator with
      wide continuous tuning of the near-infrared idler wave.
AB  - We demonstrate wide, continuous tuning of the single-frequency idler wave of a cw
      singly resonant optical parametric oscillator (SRO). The SRO consists of a
      periodically poled LiNbO(3) crystal for quasi-phase matching in a four-mirror
      signal-resonant ring cavity. The SRO, excited by 2.25 W of 924-nm radiation from
      an InGaAs diode laser, generates as much as 200 mW of single-frequency 2.1-mum
      idler radiation. We tune the idler frequency continuously within a range as large
      as 56 GHz by changing the wavelength of the diode pump laser. The versatility of
      this continuously tunable single-frequency infrared source is demonstrated by
      recording of N(2)O rovibrational absorption lines near 2.1 mum.

PMID- 18064091
TI  - Cascaded waveguide phase-matching arrangement.
AB  - We propose a new method of phase matching in nonlinear waveguides, using the
      higher-order waveguide mode as an intermediary for efficient second-harmonic or
      difference-frequency generation, and show that high conversion efficiencies can
      be achieved with this scheme.

PMID- 18064092
TI  - Multiplexed phase-conjugate holographic data storage with a buffer hologram.
AB  - We describe and demonstrate a volume holographic storage system in which a phase
      conjugate object beam is reconstructed by the same reference beam that was used
      for recording. An intermediate hologram is used as a temporary buffer, recorded
      with its own reference beam and the data-bearing object beam. Reading this buffer
      hologram with the phase conjugate of its reference beam reconstructs the phase
      conjugate of the object beam, which can then be recorded into the desired volume
      hologram for long-term storage. This method combines the immunity to lens
      aberrations provided by phase-conjugate readout with the simplicity of using the
      same multiplexed reference beam for both recording and readout. Only a single
      pair of phase-conjugate reference beams is required. Experimental results are
      shown with a single LiNbO(3):Fe crystal used as both buffer and storage holograms
      and a self-pumped phase-conjugate mirror in BaTiO(3) that provides the pair of
      phase-conjugate reference beams.

PMID- 18064093
TI  - Characterization of laser seeding by use of group-velocity dispersion in an
      atomic-vapor filter.
AB  - A method for measuring laser seeding efficiencies by use of group-velocity
      dispersion has been developed. By tuning the laser near a resonance in an atomic
      vapor filter it is possible to temporally decouple the seeded (narrow-band) light
      from the unseeded (broadband) light. We measured a seeding efficiency of 99.8% of
      the third harmonic of an injection-seeded Ti:sapphire laser. A model for the
      observed dispersion has been developed and tested. The group-velocity dispersion
      in the filter may also be used to chirp pulses for spectral analysis in the time
      domain.

PMID- 18064094
TI  - Dual-echelon single-shot femtosecond spectroscopy.
AB  - A dual-echelon technique for performing real-time pumpprobe spectroscopy with sub
      100-fs temporal resolution is demonstrated. In a single laser shot, measurements
      at 400 different temporal delays are recorded to cover a total temporal range of
      10 ps in 25-fs steps. Data from a glass sample and an explosive single crystal,
      each irradiated with intensity above the permanent damage threshold, are
      presented.

PMID- 18064095
TI  - Second-harmonic generation and wave-front correction of a terawatt laser system.
AB  - By combining second-harmonic generation and wave-front correction of a hybrid
      Ti:sapphire-Nd:glass terawatt laser chain, we were able to generate a focused
      intensity above 10(19) W/cm(2), with an estimated 10(9):1 intensity contrast
      ratio. The frequency of the laser is doubled by use of a type I KDP crystal, and
      wave-front correction is achieved with a deformable mirror coupled to a wave
      front sensor.

PMID- 18064096
TI  - Use of mass transport to reduce surface roughness in replicated gallium phosphide
      refractive microlenses.
AB  - Mass-transport smoothing has been used to reduce the surface roughness of a
      gallium phosphide (GaP) microlens from 50.0 nm (rms) to 6.5 nm (rms) while
      preserving the original surface figure. The initial GaP surface was fabricated by
      dry-etch transfer of a polymer microlens into a GaP substrate. This result
      demonstrates that mass transport can significantly improve the performance of
      economically feasible high-refractive-index micro-optical elements having
      arbitrary surface profiles.

PMID- 18064097
TI  - Experimental validation of the differential image motion lidar concept.
AB  - We have experimentally validated the concept of a differential image motion (DIM)
      lidar for measuring vertical profiles of the refractive-index structure
      characteristic C(n)(2) by building a hard-target analog of the DIM lidar and
      testing it against a conventional scintillometer on a 300-m horizontal path
      throughout a range of turbulent conditions. The test results supported the
      concept and confirmed that structure characteristic C(n)(2) can be accurately
      measured with this method.

PMID- 18064098
TI  - Generation of a 40-GHz pulse stream by pulse multiplication with a sampled fiber
      Bragg grating.
AB  - A sinc-sampled fiber Bragg grating is used to achieve multiplication of the
      repetition rate of a pulse stream from 10 to 40 GHz. The spectral characteristics
      of the grating ensure that the resultant pulses-solitons of 3.4-ps width-have the
      same individual pulse characteristics as those of the input.

PMID- 18064099
TI  - Reconfigurable time-domain spectral shaping of an optical pulse stretched by a
      fiber Bragg grating.
AB  - We demonstrate a method for spectrally shaping optical pulses that is readily
      reconfigurable and can produce variable filter functions. This practical
      technique relies on a compact and robust 3.86-m-long linearly chirped fiber Bragg
      grating that chromatically disperses the pulse to ~30 ns. We then shape the pulse
      envelope, and thus the pulse spectrum, with a programmable arbitrary waveform
      generator and an amplitude modulator to obtain several filter functions.

PMID- 18064100
TI  - Ultraviolet-initiated reactions of H(2) with germanosilicate fibers and H(2)
      concentration dependence of the Bragg wavelength of a fiber grating.
AB  - We present a model with which to calculate the index increase induced in standard
      single-mode fiber by hydrogen loading. Also, we propose that the dominant
      products of reaction in UV-written hydrogenated standard communication fibers are
      GeE? and Si-OH. Based on the above models, we calculate the Bragg wavelength
      shifts that are due to hydrogen diffusion out of the fiber gratings. The relative
      effective index change that is due to hydrogen dissolved in fiber can be as much
      as 6 x 10(-4) if standard telecom fiber is hydrogen loaded with a concentration
      of ~1.44 mol.%. Theoretical results agree with experimental results.

PMID- 18064101
TI  - Split-step time-domain analysis of optical waveguide devices composed of a
      directional coupler and gratings.
AB  - An extended split-step time-domain model for composite coupling structures is
      reported. Time-dependent coupled-wave equations are solved by splitting of the
      operators for phase accumulation, forward directional coupling, and reverse Bragg
      reflection. Through an analysis of an add-drop filter based on a grating-written
      directional-coupler structure, the proposed modeling method is shown to be an
      order of magnitude more efficient than the previous methods.

PMID- 18064102
TI  - Fiber-optic tunable loop mirror using Berry's geometric phase.
AB  - A method is presented for constructing a fiber-optic loop mirror whose
      reflectivity is tunable even though a fixed-ratio directional coupler is used.
      The tunability is polarization and wavelength independent and depends only on the
      geometry of the fiber-tuning element. This loop mirror can be used to transfer
      energy from one channel to another in a controllable way. We experimentally
      demonstrate the tunable reflectivity and present some experimental
      investigations.

PMID- 18064103
TI  - Nonlinear switching in a 20-cm-long fiber Bragg grating.
AB  - We report experimental observation of nonlinear all-optical switching of a 20-cm
      long fiber Bragg grating. The grating is self-switched owing to the optical Kerr
      effect and in the nonlinear regime shows a 20-dB increase in transmissivity. This
      increase is a marked improvement from the switching results obtained from shorter
      gratings.

PMID- 18064104
TI  - Sensitivity improvement in two-center holographic recording.
AB  - Persistent holograms are recorded with green light in LiNbO(3) crystals doped
      with Mn and Fe. The recording sensitivity is 20 times better than that obtained
      by recording with red light. Partial loss of persistence is caused by using green
      light for recording.

PMID- 18064105
TI  - Reentrant two-mirror ring resonator for generation of a single-frequency green
      laser.
AB  - A nonplanar, reentrant two-spherical-mirror ring cavity is demonstrated. It is
      compact and free of astigmatism. Unidirectional operation is achieved by use of
      reciprocal and nonreciprocal polarization rotators to differentiate round-trip
      loss. A single-frequency green laser is generated by intracavity frequency
      doubling. Amplitude noise as low as 0.25% is achieved.

PMID- 18064106
TI  - Statistics and reduction of speckle in optical coherence tomography.
AB  - Studies have shown that optical coherence tomography (OCT) is useful in imaging
      microscopic structures through highly scattering media. Because spatially
      coherent light is used in OCT, speckle in the reconstructed image is unavoidable,
      resulting in degradation of the quality of the OCT images and impaired ability to
      differentiate subsurface structures. Therefore speckle reduction is an important
      issue in OCT imaging. We develop speckle statistics that are appropriate to the
      OCT measurements and demonstrate a simple and practical speckle-reduction
      technique.

PMID- 18064107
TI  - Geometrical cross-sectional imaging by a heterodyne wavelength-scanning
      interference confocal microscope.
AB  - We developed a heterodyne interference confocal microscope, using wavelength
      modulation of a laser diode to realize quick separate measurement of the
      refractive indices and geometrical thicknesses of multiple layers. This
      microscope requires only a single axial movement of the specimen. We can display
      the geometrical cross sections of the interfaces and the refractive indices of a
      three-layered object.

PMID- 18064108
TI  - Prescription for optimizing holograms in LiNbO(3):Fe:Mn.
AB  - The photorefractive holographic dynamics of grating formation in photochromic
      doubly doped LiNbO(3):Fe:Mn crystal is studied numerically and analytically in
      terms of the two-center model of Kukhtarev et al. [Ferroelectrics 22, 949
      (1979)]. The relations among the recorded and fixed space-charge fields and the
      doping densities, the oxidation-reduction states of the fields, and the
      intensities of UV-sensitizing and red recording beams are studied. Important
      conditions and effects are found, and an optimal prescription for material doping
      and oxidation-reduction processing is suggested in which the crystal can be
      strongly oxidized and the Mn-doping density is smaller than the Fe-doping
      density.

PMID- 18064109
TI  - Wavelength conversion in GaAs micro-ring resonators.
AB  - Tightly confined, low-loss waveguides in highly nonlinear materials permit
      nonlinear optical interactions to occur over much shorter distances than do
      fibers. The nonlinear interactions are further enhanced in resonators. Both
      theory and experiment of enhanced four-wave mixing in micro-ring resonators are
      presented that can be used for many applications. A conversion efficiency of 14%
      achievable with only 10-mW peak pump power is predicted under realizable
      conditions. The experiment, the first one to the authors' knowledge in nonlinear
      optics performed in micro-rings, shows, even in a lossy GaAs/AlGaAs ring, a 26-dB
      improvement in the conversion efficiency compared with that of an equivalent
      straight waveguide, in agreement with theory.

PMID- 18064110
TI  - Microlaser-pumped periodically poled lithium niobate optical parametric generator
      optical parametric amplifier.
AB  - For what is believed to be the first time, a single-longitudinal-mode passively Q
      switched Nd:YAG microlaser is used to pump a narrow-bandwidth periodically poled
      lithium niobate (PPLN) optical parametric generator-optical parametric amplifier
      (OPG-OPA). Before amplification in the OPA, the output of the OPG stage was
      spectrally filtered with an air-spaced etalon, resulting in spectroscopically
      useful radiation (bandwidth, ~0.05 cm(-1) FWHM) that was tunable in 15-cm(-1)
      segments anywhere in the signal range 6820-6220 cm(-1) and the idler range 2580
      3180 cm(-1). The ability to pump an OPG-OPA with compact, high-repetition-rate,
      intrinsically narrow-bandwidth microlasers is made possible by the high gain of
      PPLN. The result is a tunable light source that is well suited for use in
      portable spectroscopic gas sensors.

PMID- 18064111
TI  - Collisions and inhomogeneous forces between solitons of different dimensionality.
AB  - We exploit nonlinear propagation in photorefractive crystals to observe the
      phenomenology associated with the collision and interaction of solitons of
      different tranverse dimensions: a self-trapped stripe and a round soliton. Along
      with evidence of particlelike behavior, our results indicate the emergence of a
      new phenomenology related to the hybrid-dimensional system.

PMID- 18064113
TI  - Phase-only optical encryption.
AB  - We have implemented a phase-only optical encryption and decryption system with a
      readout based on the generalized phase-contrast method. The experimental system
      has been implemented with liquid-crystal spatial light modulators to generate
      binary phase-encrypted masks and a decrypting key. A phase-contrast filter is
      used to display the phase information.

PMID- 18064112
TI  - Spectrally coded optical data storage by metal nanoparticles.
AB  - In metal nanoparticles the resonance wavelength of light-driven collective
      electron oscillations is determined by the particle shape. This shape dependence
      can be used for optical data storage by spectral coding. In this way the storage
      density can be increased by at least a factor of 5 compared with that for
      conventional optical storage principles.

PMID- 18064114
TI  - Dispersion resulting from phase and amplitude errors in arrayed-waveguide grating
      multiplexers-demultiplexers.
AB  - We report dispersion resulting from phase and amplitude errors in arrayed
      waveguide grating (AWG) multiplexers-demultiplexers. We measure the phase- and
      amplitude-error distributions of two different types of AWG and discuss their
      effects on the dispersion. The results show that the origin of the dispersion in
      the AWG is the low-order Fourier components of the symmetric phase and the
      antisymmetric amplitude errors. We also discuss the dependence of the dispersion
      on the passband shape in the presence of the same fabrication errors.

PMID- 18064115
TI  - Subhertz spectral fluctuations from high-density excitons in coupled quantum
      wells.
AB  - In 1994 Butov et al. [Phys. Rev. Lett. 73, 304 (1994)] reported large, extremely
      low-frequency fluctuations in the luminescence intensity from indirect excitons
      in a coupled quantum well. We have reproduced these fluctuations in a similar
      structure. Our observations indicate, however, that the fluctuations are spectral
      fluctuations rather than intensity fluctuations. We have eliminated several
      possible causes for the fluctuations and propose a possible cause.

PMID- 18064116
TI  - Amplitude and phase control of ultrashort pulses by use of an acousto-optic
      programmable dispersive filter: pulse compression and shaping.
AB  - We demonstrate experimentally that an arbitrary phase and amplitude profile can
      be applied to an ultrashort pulse by use of an acousto-optic programmable
      dispersive filter (AOPDF). Our filter has a large group-delay range that extends
      over 3 ps and a 30% diffraction efficiency over 150 THz. Experiments were
      conducted on a kilohertz chirped-pulse amplification laser chain capable of
      generating 30-fs pulses without additional pulse shaping. Compensating for gain
      narrowing and residual phase errors with an AOPDF in place of the stretcher
      results in 17-fs transform-limited pulses. Arbitrary shaping of these 17-fs
      pulses is also demonstrated in both the temporal and the spectral domains.

PMID- 18064117
TI  - Single-shot chirped-pulse spectral interferometry used to measure the femtosecond
      ionization dynamics of air.
AB  - A novel interferometry technique is presented by which, in one shot, one can
      measure phase changes with a resolution of tens of femtoseconds while extending
      the measurement over picoseconds or even longer. The method is based on spectral
      (frequency-domain) interferometry with a pair of linearly chirped pules as
      probes. With this technique we obtained single-shot measurements of the rapid
      phase changes induced by optical field ionization of air. This allowed us to
      calculate the time profile of the electron density created by an intense short
      laser pulse.

PMID- 18064118
TI  - Dual-wavelength chirped-pulse amplification system.
AB  - We demonstrate a chirped-pulse amplification system that simultaneously amplifies
      two pulses from a dual-wavelength oscillator in a single regenerative amplifier.
      The two wavelengths can be tuned from 800 to 890 nm. The total energy of 1.5 mJ
      can be variably split between the two pulses. The pulses are 150 fs in duration
      and have 60-fs timing jitter.

PMID- 18064119
TI  - Femtosecond Cr(4+):YAG laser with an L-fold cavity operating at a 1.2-GHz
      repetition rate.
AB  - Pulses of 55-fs width and 1.2-GHz repetition rate at 1.52 mum are generated from
      an L-fold cavity Cr(4+):YAG laser by optimization of the lasing-beam mode inside
      the gain medium. The pulse width is comparable with that obtained from a standard
      Z-fold cavity. The pulses are characterized by a second-harmonic-generation
      frequency-resolved optical gating method. The pulse shape deviates from a sech(2)
      function because of its broad shoulders. With further miniaturization it should
      be possible to extend the Cr(4+):YAG mode-locked operation to multigigahertz
      rates.

PMID- 18064120
TI  - Adaptive pulse compression for transform-limited 15-fs high-energy pulse
      generation.
AB  - We demonstrate the use of a deformable-mirror pulse shaper, combined with an
      evolutionary optimization algorithm, to correct high-order residual phase
      aberrations in a 1-mJ, 1-kHz, 15-fs laser amplifier. Frequency-resolved optical
      gating measurements reveal that the output pulse duration of 15.2 fs is within
      our measurement error of the theoretical transform limit. This technique
      significantly reduces the pulse duration and the temporal prepulse energy of the
      pulse while increasing the peak intensity by 26%. It is demonstrated, for what is
      believed to be the first time, that the problem of pedestals in laser amplifiers
      can be addressed by spectral-domain correction.

PMID- 18064121
TI  - Surface-plasmon-assisted resonant tunneling of light through a periodically
      corrugated thin metal film.
AB  - We present experimental results and a numerical model confirming that surface
      plasmons can resonantly enhance light transmission through a corrugated metal
      film. A new interpretation in terms of plasmon-assisted light tunneling is given
      to recent experiments on light penetration through periodic subwavelength holes
      in a thin metal film. We designed a narrow-band filter suitable for applications
      in optical communication by optimizing the film and the grating parameters.

PMID- 18064122
TI  - Differential theory for diffraction gratings: a new formulation for TM
      polarization with rapid convergence.
AB  - A new formulation of the differential method in TM polarization, based on correct
      representation of truncated Fourier series of products of discontinuous
      functions, is proposed. Although the derived equations are more complicated than
      in the classical formulation, the convergence rate with respect to the truncation
      parameter (with the number of diffraction orders taken into account) is much
      faster for arbitrary grating profiles, approaching the convergence rate in TE
      polarization. Numerical examples are presented for dielectric and metallic
      sinusoidal gratings with a 100% modulation ratio.

PMID- 18064123
TI  - Shock-wave-assisted ultrafast soliton generation.
AB  - It is predicted numerically that soliton generation by four-wave mixing when the
      central wavelength of the initial pulse is below the zero-dispersion point of a
      nonlinear waveguide can be significantly boosted by shock-wave formation that
      reduces the launching power and extends the efficiency of that process deep
      inside the normal-dispersion region. Experimental evidence of the validity of
      this prediction is provided by spectral phase and intensity measurement of the
      propagated bound-state pulse.

PMID- 18064124
TI  - Cross-phase modulation and multiwavelength adiabatic solitons.
AB  - In an experimental demonstration of four-channel, wavelength-division-multiplexed
      repeaterless transmission over 235 km, adiabatic soliton propagation allows for
      precise spectral characterization of cross-phase modulation effects during
      initial soliton collisions. Theoretical predictions of the spectral shifts that
      occur are verified for ultrashort solitons. The relationship between the
      frequency shift and the initial pulse separation is confirmed by measurement of
      the bit-error ratio as the pulse spacing is varied at the fiber input. Adiabatic
      expansion of narrow solitons may help to alleviate the channel restrictions that
      are required for prevention of soliton collisions at the fiber input.

PMID- 18064125
TI  - Holographic recording in a photopolymer by optically induced detachment of
      chromophores.
AB  - We demonstrate holographic recording in a new photopolymer system. The recording
      material is created by copolymerization of an optically inert monomer, methyl
      methacrylate, and a second monomer that is optically sensitive. On exposure of
      the recording material to light, a portion of the optically sensitive component
      detaches from the polymer matrix and causes hologram amplification through
      diffusion of the free molecules. We measured postrecording grating amplifications
      as high as 170% by this process. The recorded holograms are persistent at room
      temperature under continuous illumination at the recording wavelength.

PMID- 18064126
TI  - Three-dimensional object recognition by use of digital holography.
AB  - We present a technique for performing three-dimensional (3D) pattern recognition
      by use of in-line digital holography. The complex amplitude distribution
      generated by a 3D object at an arbitrary plane located in the Fresnel diffraction
      region is recorded by phase-shifting interferometry. The digital hologram
      contains information about the 3D object's shape, location, and orientation. This
      information allows us to perform 3D pattern-recognition techniques with high
      discrimination and to measure 3D orientation changes. Experimental results are
      presented.

PMID- 18064127
TI  - Scanning Michelson interferometer for imaging surface acoustic wave fields.
AB  - A scanning homodyne Michelson interferometer is constructed for two-dimensional
      imaging of high-frequency surface acoustic wave (SAW) fields in SAW devices. The
      interferometer possesses a sensitivity of ~10(-5)nm/ radicalHz , and it is
      capable of directly measuring SAW's with frequencies ranging from 0.5 MHz up to 1
      GHz. The fast scheme used for locating the optimum operation point of the
      interferometer facilitates high measuring speeds, up to 50,000 points/h. The
      measured field image has a lateral resolution of better than 1 mu;m . The fully
      optical noninvasive scanning system can be applied to SAW device development and
      research, providing information on acoustic wave distribution that cannot be
      obtained by merely electrical measurements.

PMID- 18064128
TI  - Passive Q switching and self-frequency Raman conversion in a diode-pumped
      Yb:KGd(WO(4))(2) laser.
AB  - We report on the laser performance of a diode-pumped Yb:KGd(WO(4))(2) laser that
      is passively Q switched with a Cr(4+):YAG saturable absorber. Raman conversion of
      fundamental laser emission in the laser crystal was demonstrated. Q-switched 3.4
      mu;J pulses with a pulse width of 85 ns were obtained at the 1033-nm fundamental
      wavelength and 0.4-mu;J pulses with a pulse width of 20 ns were produced in a
      first Stokes at 1139 nm.

PMID- 18064129
TI  - Room-temperature operation of a multiwatt Tm:YAG laser pumped by a 1-mum Nd:YAG
      laser.
AB  - We present what is to our knowledge the first demonstration of a 4.7-W cw Tm:YAG.
      This proof-of-principle experiment clearly demonstrates the possibility of using
      a pump absorption that is 2 orders of magnitude (~0.0078 cm(-1)) less than that
      of the conventional pump absorption (typically >1 cm(-1)). This Tm:YAG laser is
      pumped intracavity within a Nd:YAG laser for multiple-pass absorption. The
      maximum conversion efficiency of 2.02 mum is 20%, with a slope efficiency of 35%
      with respect to the absorbed 1.064-mum power.

PMID- 18064130
TI  - Three-level Q-switched laser operation of ytterbium-doped Sr(5)(PO(4))(3)F at 985
      nm.
AB  - Ytterbium-doped Sr(5)(PO(4))(3)F was successfully lased at 985 nm in quasi-cw
      mode with a slope efficiency of 74% and an absorbed threshold energy of 18 mJ. Q
      switched slope efficiencies of 21% were obtained with a maximum energy of 9.4 mJ
      in 8.8-ns pulses.

PMID- 18064131
TI  - Experimental synchronization of chaotic oscillations in external-cavity
      semiconductor lasers.
AB  - Synchronization of fast chaotic oscillations of the order of gigahertz is
      experimentally observed in two external-cavity semiconductor lasers.

PMID- 18064132
TI  - Resolution enhancement in a reflection mode near-field optical microscope by
      second-harmonic modulation signals.
AB  - The motion of the probe tip in a near-field scanning optical microscope, dithered
      by vibration of a tuning fork, can modulate the reflection signal from the sample
      surface not only at the fundamental dithering frequency but also at its second
      harmonic. By lock-in amplification of these modulated signals, enhanced optical
      images are obtained, even with an uncoated fiber probe. In particular, accurate
      optical images with higher resolution are obtained when the second-harmonic
      signal is detected, which results from the parametric modulation of the tip
      sample separation at the double frequency of the horizontal dithering motion of
      the tip. Using a DVD ROM with a track pitch of 0.74 mum as a test sample, we
      observed that the sharp edges around the pits are clearly resolved with the
      second-harmonic signals and obtained enhanced resolution of ~70 nm full width at
      half-maximum.

PMID- 18064133
TI  - Field-enhanced scanning optical microscope.
AB  - We present experimental results of an imaging technique that uses as a local
      probe the optical field enhanced at the junction of a scanning tunneling
      microscope illuminated by a p-polarized laser beam. Images of highly oriented
      pyrolithic graphite, recorded at a constant height mode, show a lateral optical
      resolution of as much as 10 nm. Approach curves exhibit sensitivity on a
      subnanometer scale of the optical signal to the tip-sample distance, yielding the
      ultrahigh vertical resolution reached in the images.

PMID- 18064134
TI  - Theoretical study of detection of a dipole emitter through an objective with high
      numerical aperture.
AB  - The problem of detecting electric dipole emitters (such as a fluorescing
      molecule) through a microscope objective with a high numerical aperture is
      considered. Exact vector-wave-optics results of the field distribution of the
      electromagnetic field in image space are derived. On the basis of these results,
      the collection-efficiency function (CEF) is calculated. This calculation is
      compared with a semigeometric approximation of the CEF, for which a new
      analytical formula is presented. The derived results are important for
      applications such as fluorescence correlation spectroscopy and single-molecule
      fluorescence detection with a confocal microscope.

PMID- 18064135
TI  - Quasi interference of perpendicularly polarized guided modes observed with a
      photon scanning tunneling microscope.
AB  - The simultaneous detection of TE- as well as TM-polarized light with a photon
      scanning tunneling microscope leads to a quasi-interference pattern of these
      mutually perpendicular polarized fields. This interference pattern has been
      observed in the optical field distribution as a function of both position and
      wavelength. Comparison of experimental data with simulations confirms the
      interference of mutually orthogonal fields. This quasi interference is caused by
      conversion of the linearly polarized light of both modes into elliptically
      polarized light by a fiber probe.

PMID- 18064136
TI  - Nanoscale nonlinear optical process: theoretical modeling of second-harmonic
      generation for both forbidden and allowed light.
AB  - Based on a combination of the multiple-multipole method and nonlinear coupled
      wave equations, a rigorous three-dimensional numerical simulation of nonlinear
      optical interactions between an optical near field and a nonlinear medium is
      performed, allowing us to study the dependence of second-harmonic (SH) near-field
      intensity on tip-sample distance and the polarization state of the incident
      fundamental wave. It is demonstrated that allowed and forbidden light make
      different contributions to the SH near-field intensity.

PMID- 18064137
TI  - Vector solitons in (2 + 1) dimensions.
AB  - We address the problem of the existence and stability of vector spatial solitons
      formed by two incoherently interacting optical beams in bulk Kerr and saturable
      media. We identify families of (2+1)-dimensional two-mode self-trapped beams,
      with and without a topological charge, and describe their properties analytically
      and numerically.

PMID- 18064139
TI  - Improved analog optical link performance with quantum phase amplification.
AB  - A degenerate parametric amplifier at the transmitter can improve the power
      efficiency of a small-signal phase-modulated optical transmission system by
      acting as a phase amplifier. For a parametric power gain H, the total transmitter
      power requirement is reduced by a factor of H(2) compared with that of a
      conventional phase-modulated system.

PMID- 18064138
TI  - 1.5-mum emissions from laser-diode-pumped Nd-doped microchip solid-state lasers.
AB  - 1.5-mum emissions from Nd:YAG, Nd:YVO(4), and LiNdP(4) O>(12) microchip lasers
      pumped by laser diodes have been observed. These coherent emissions are
      attributed to the effect of high-energy modified lattice vibration owing to the
      existence of Nd ions as well as to stimulated intracavity Raman scattering
      enhanced by the microchip configuration. A four-wave mixing process involving two
      lasing fields and a Stokes field was identified as the generator of new adjacent
      1.5-mu;m emission.

PMID- 18064140
TI  - Quasi-phase-matched optical parametric oscillation with periodically poled
      stoichiometric LiTaO(3).
AB  - We have demonstrated, for the first time to our knowledge, periodic poling of a 2
      mm-thick near-stoichiometric LiTaO(3) substrate and its operation in a nanosecond
      optical parametric oscillator. Because the coercive field of stoichiometric
      LiTaO(3) is ~2 kV/mm , which is approximately one tenth that of the conventional
      congruent field, periodic poling of thicker stoichiometric substrates was
      successfully performed by means of an electric-field poling process at room
      temperature. The performance of a parametric oscillator with a 1-mm-thick sample
      was compared with that of the oscillator with the periodically poled congruent
      oscillator. The stoichiometric device exhibited better performance.

PMID- 18064141
TI  - Modification of pattern formation in doubly resonant second-harmonic generation
      by competing parametric oscillation.
AB  - We analyze pattern formation in doubly resonant intracavity second-harmonic
      generation in the presence of competing nondegenerate parametric downconversion.
      We show that for positive cavity detuning of the fundamental frequency the
      threshold for parametric oscillation is lower than that of transverse, pattern
      forming instabilities. The parametric oscillation strongly modifies the pattern
      dynamics found previously in a simplified analysis that neglects parametric
      instability [Phys. Rev. E 56, 4803 (1997)]. Stationary and dynamic patterns in
      the presence of parametric oscillation are found numerically.

PMID- 18064142
TI  - 2.5-GHz repetition-rate singly resonant optical parametric oscillator
      synchronously pumped by a mode-locked diode oscillator amplifier system.
AB  - We report on an optical parametric oscillator (OPO) that is synchronously pumped
      directly by a diode laser. This laser is an actively mode-locked master
      oscillator power-amplifier system that produces 20-ps pulses at 927 nm with a
      repetition rate of 2.5 GHz and an average power of 0.9 W. The OPO, which is a
      singly resonant device based on periodically poled lithium niobate, generates 7.8
      ps pulses. The OPO threshold is 300 mW of average pump power, and the maximum
      average idler output power is 78 mW at a wavelength of 2100 nm. By changing the
      crystal temperature we can wavelength tune the output in the ranges 1530-1737 nm
      (signal) and 1986-2348 nm (idler). Rapid wavelength tuning of the OPO over 46 nm
      (signal) and 74 nm (idler) is achieved through tuning the cavity length over 28
      microm by use of a piezoelectric transducer.

PMID- 18064143
TI  - Linear and nonlinear waveguides induced by optical vortex solitons.
AB  - We study, numerically and analytically, linear and nonlinear waveguides induced
      by optical vortex solitons in a Kerr medium. Both fundamental and first-order
      guided modes are analyzed, as well as cases of effective defocusing and focusing
      nonlinearity.

PMID- 18064144
TI  - Light beams with minimum phase space product.
AB  - We derive a reciprocity inequality involving the product of the effective size of
      a statistically stationary, planar, secondary source of any state of coherence
      and of the angular spread of the far-zone intensity generated by the source. We
      show that of all possible such sources, the fully spatially coherent lowest-order
      Hermite-Gaussian laser mode has the smallest possible reciprocity product.

PMID- 18064145
TI  - Cavity ringdown spectroscopy using mid-infrared quantum-cascade lasers.
AB  - Cavity ringdown spectra of ammonia at 10 parts in 10(9) by volume (ppbv) and
      higher concentrations were recorded by use of a 16-mW continuous-wave quantum
      casacde distributed-feedback laser at 8.5 mum whose wavelength was continuously
      temperature tuned over 15 nm. A sensitivity (noise-equivalent absorbance) of
      3.4x10(-9) cm(-1) Hz(-1/2) was achieved for ammonia in nitrogen at standard
      temperature and pressure, which corresponds to a detection limit of 0.25 ppbv.

PMID- 18064146
TI  - Measuring time-domain optical response functions with an optimized sampling rate.
AB  - We propose a time-domain interferometry method that circumvents the usual
      sampling rate condition. It was devised for the retrieval of fast optical
      response functions in low-repetition-rate experiments. Its potential temporal
      dynamic range matches the spectral resolution and bandwidth requirements of the
      arbitrarily shaped spectral filters that are engraved in amorphous spectral hole
      burning materials.

PMID- 18064147
TI  - Optical pulse compression: bulk media versus hollow waveguides.
AB  - Optical pulse-compression systems based on bulk materials and hollow waveguides
      are compared by use of coupled-mode theory. Our analysis reveals an intuitive
      picture of the temporal and spatial nonlinear processes involved in pulse
      compression. Further, simple formulas are derived that give an estimate of the
      spatial distortions and of the self-phase modulation induced by Kerr
      nonlinearity. Finally, a parameter regime is identified in which self-focusing in
      bulk media is suppressed, resulting in a substantial improvement in the spatial
      beam quality of the compressed pulses.

PMID- 18064148
TI  - Use of the organic crystal DAST for terahertz beam applications.
AB  - We report the use of the organic crystal DAST as a freely propagating
      electromagnetic-wave sensor at terahertz (THz) frequency. We also report the
      result of using a DAST crystal as a mid-IR THz emitter. Compared with the optical
      rectification from our best ZnTe emitter, that obtained by use of DAST
      demonstrates a sixfold enhancement of radiation at 7-20 THz.

PMID- 18064149
TI  - Membrane imaging by simultaneous second-harmonic generation and two-photon
      microscopy: errata.

PMID- 18064150
TI  - Bichromatic two-photon coherent excitation of sodium to provide a dual-wavelength
      guidestar.
AB  - A bichromatic sodium guide star based on two-photon coherent excitation followed
      by cascade emission is considered. Results of density matrix computations,
      including Doppler averaging, are presented for both a three-level model and the
      full hyperfine structure of the sodium 3S, 3P, and 4S levels. These results
      indicate that the proposed scheme for a bichromatic guide star is feasible.

PMID- 18064151
TI  - Water-vapor mixing-ratio measurements in the solar-blind region.
AB  - It is shown that, under clear sky conditions, water-vapor mixing-ratio
      measurements by solar-blind Raman lidars can be improved if the differential
      transmissivity is calculated by use of a single Raman signal instead of the usual
      Raman differential absorption lidar method, which allows one to exploit the large
      absorption cross section of ozone in this spectral region. We present a
      discussion of statistical and systematic errors in both methods and show the
      results of a numerical simulation.

PMID- 18064152
TI  - Particulate concentration measured from scattered light fluctuations.
AB  - Scintillation of scattered radiation caused by particulate matter is studied. By
      use of stochastic theory, expressions for mathematical expectation, variance, and
      scintillation index are derived. A method of measuring particulate-mass
      concentration with the scintillation index is proposed. The major advantage of
      this method is its insensitivity to lens contamination and particle-color change.

PMID- 18064153
TI  - Annealing properties of gratings written into UV-presensitized hydrogen
      outdiffused optical fiber.
AB  - Accelerated aging of gratings written in UV presensitized hydrogen outdiffused
      optical fibers show that these gratings are more stable than standard gratings
      written in hydrogen-loaded fibers. They are observed to grow initially by as much
      as 2%. The predicted decay after 25 years at 80 degrees C is ~0.1% . The results
      suggest that the index modulation decay is so slow that postfabrication annealing
      can be avoided.

PMID- 18064154
TI  - All-fiber system for simultaneous interrogation of distributed strain and
      temperature sensing by spontaneous Brillouin scattering.
AB  - We demonstrate a low-loss, long-range, single-ended distributed optical fiber
      sensor to measure both temperature and strain simultaneously and unambiguously.
      By using the Landau?Placzek ratio and cascaded Mach?Zehnder interferometric
      filters, we measure both the intensity and the frequency changes in the Brillouin
      backscattered signal. Strain and temperature measurements can then be
      independently resolved. A temperature resolution of 4 degrees C, a strain
      resolution of 290 muepsilon, and a spatial resolution of 10 m have been achieved
      for a sensing length of 15 km.

PMID- 18064155
TI  - Reconstructing arbitrary strain distributions within fiber gratings by time
      frequency signal analysis.
AB  - We apply time-frequency signal-analysis techniques to recover arbitrary
      distributions of axial strain along a fiber grating from its reflection spectral
      response. The proposed method permits accurate strain reconstruction with no
      restrictions on the applied strain profile or on the grating length. We
      demonstrate the validity and accuracy of the technique by reconstructing the
      strain field in a fiber grating with a nonmonotonic strain profile, which
      includes all the following: a constant strain section, high gradient variations,
      and strain discontinuities.

PMID- 18064156
TI  - Fundamental information-density limits in optically amplified transmission: an
      entropy analysis.
AB  - Fundamental information-density limits are evaluated for amplified systems, based
      on entropy analysis. It is shown that in-line amplification introduces
      information loss, which is more important in distributed than in lumped
      amplification. In the absence of any other degradation (such as that which comes
      from dispersion and nonlinearity), spectral efficiencies of 6?14 (bits/s)/Hz
      represent theoretical limits for medium- and long-haul amplified systems.

PMID- 18064157
TI  - Demonstration of massive wavelength-division multiplexing over transoceanic
      distances by use of dispersion-managed solitons.
AB  - By combining a special dispersion map that has nearly constant path-average
      dispersion, a hybrid amplification scheme involving backward-pumped Raman gain,
      and sliding-frequency guiding filters, we have demonstrated massive wavelength
      division multiplexing at 10 Gbits/s per channel, error free (bit-error rate,
      </=1x10(-9) for all channels), without the use of forward error correction, over
      greater than 9000 km, using dispersion-managed solitons. The number of channels
      (27) was limited only by a temporary lack of amplifier power and gain flatness.
      Terabit capacities are to be expected in the near future.

PMID- 18064158
TI  - Study of the frequency autocorrelation of the differential group delay in fibers
      with polarization mode dispersion.
AB  - We study the frequency autocorrelation of the differential group delay (DGD) in
      fibers with polarization mode dispersion (PMD). We show that the correlation
      bandwidth of the DGD is comparable with that of the orientation of the PMD
      vector. Furthermore, we show that all the most general statistical properties of
      polarization mode dispersion in long fibers are uniquely determined by the mean
      DGD. An estimate of the accuracy of measurements in which the mean DGD is
      extracted by frequency averaging in a single fiber is obtained as a function of
      the measured bandwidth.

PMID- 18064160
TI  - Distortions in pixel-matched holographic data storage due to lateral dimensional
      change of photopolymer storage media.
AB  - Dimensional changes in polymerizable storage materials during exposure are a
      source of pixel misregistration in digital holographic storage. Lateral shrinkage
      or expansion of photopolymer recording materials can be deduced from quantitative
      measurement of the shift and the magnification errors of reconstructed holograms.

PMID- 18064159
TI  - Tunable mechanically induced long-period fiber gratings.
AB  - We report the experimental characterization of mechanically induced long-period
      fiber gratings (LPFG's) made by pressing a plate with periodic grooves against a
      short length of fiber. This filter, which is simple and inexpensive, exhibits
      transmission spectra and temperature stability similar to those of photoinduced
      LPFG's. It also offers the unique advantages of being tunable, erasable, and
      reconfigurable. Its polarization dependence also makes it useful as a polarizer,
      although it can also be eliminated with simple mechanical designs.

PMID- 18064161
TI  - Numerical heterodyne holography with two-dimensional photodetector arrays.
AB  - We present an original heterodyne holography method for digital holography that
      relies on two-dimensional heterodyne detection to record the phase and the
      amplitude of a field. The technique has been tested on objects as much as 13 mm
      in size. Consistency checks were performed, and high-resolution images were
      computed. We show the requirement for a spatial filter to select properly sampled
      near-axis photons. Heterodyne holography is superior to off-axis digital
      holography for both field of view and resolution.

PMID- 18064162
TI  - Ultrahigh-resolution plastic graded-index fused image plates.
AB  - Fiber-optic imaging systems such as the medical endoscope, the boroscope, the
      fused-image faceplate, and the image conduit are now made from glass step-index
      (SI) fibers, and the image resolution of the SI fiber-optic imaging systems is
      limited to ~5 microm. Ultrahigh-resolution fiber-optic fused-image plates with
      fiber diameter sizes of 5 and 2.8 microm were fabricated with plastic graded
      index (GRIN) fibers. The measured image resolutions of the 5-microm SI and GRIN
      based guides were comparable, and the resolution of the plastic GRIN image guides
      improved as the fiber diameter was reduced from 5 to 2.8 microm.

PMID- 18064163
TI  - Polarization Sagnac interferometer with a reflective grating beam splitter.
AB  - All-reflective interferometric gravitational-wave detector configurations with a
      diffraction grating as a power beam splitter have been proposed to reduce thermal
      lensing. We demonstrate the use of a diffraction grating as a polarization beam
      splitter in a zero-area polarization Sagnac interferometer.

PMID- 18064164
TI  - 3.3-microm microcavity light emitter for gas detection.
AB  - A room-temperature resonant-cavity light source emitting at 3.327 microm is
      presented. It combines a CdHgTe light-emitting layer, grown by molecular beam
      epitaxy, and two evaporated YF(3)-ZnS Bragg mirrors. The emitter is optically
      pumped by a commercial low-power GaAs laser diode. Compared with an unprocessed
      sample, this microcavity device shows a drastic (10-fold) linewidth reduction, a
      3.3-fold intensity increase at 3.327 microm , and a 2.4-fold angular-spread
      decrease. The emitted optical power is 15 microW , and the device is used as a
      light source in a basic gas-detection setup. Measurements of a butane-propane
      mixture in the 1 to 5x 10(-3) bar range with a 5-cm-long single-path gas cell are
      demonstrated.

PMID- 18064165
TI  - Dispersion-mode pulsed laser.
AB  - A new self-consistency condition in pulsed lasers with strong intracavity
      dispersion imposes dispersion modes with specific cavity-length dependent pulse
      rates, utilizing pulse-train self-imaging properties of a temporal Talbot effect.
      We give an experimental demonstration of such a laser operation, using a long
      fiber cavity. We also demonstrate temporal Talbot imaging of a train of short
      pulses that propagate along large distances of dispersive fibers.

PMID- 18064166
TI  - Efficient continuous-wave self-frequency-doubling green diode-pumped
      Yb:YAl(3)(BO(3))(4) lasers.
AB  - Efficient cw self-frequency-doubled green laser output of 160 mW has been
      obtained from Yb:YAl(3)(BO(3))(4) crystal pumped by 1.4-W incident power from a
      fiber-coupled 976-nm laser diode. The incident-pump-power-green-output-power
      conversion efficiency is greater than 11.3%, and the electrical-input-green
      conversion efficiency is 3.9%. Tunable green output from 513.0 to 545.8 nm is
      also demonstrated with a quartz birefringent filter.

PMID- 18064167
TI  - Frequency-swept ultrasound-modulated optical tomography in biological tissue by
      use of parallel detection.
AB  - A frequency-swept ultrasonic beam was focused into a biological tissue sample to
      modulate the laser light passing through the ultrasonic beam inside the tissue.
      Parallel detection of the speckle field formed by the transmitted laser light was
      implemented with the source-synchronous-illumination lock-in technique to improve
      the signal-to-noise ratio. The ultrasound-modulated laser light reflects the
      local optical and mechanical properties in the ultrasonic beam and can be used
      for tomographic imaging of the tissue. Sweeping the ultrasonic frequency provides
      spatial resolution along the ultrasonic axis, which is scalable with the
      frequency span of the sweep. Two-dimensional images of biological tissue with
      buried objects were successfully obtained experimentally.

PMID- 18064168
TI  - Cylindrical KTiOPO(4) crystal for enhanced angular tunability of phase-matched
      optical parametric oscillators.
AB  - We demonstrate what is to our knowledge the first optical parametric oscillator
      (OPO) based on a cylindrical phase-matched nonlinear crystal. Experiments are
      performed with an uncoated KTiOPO(4) crystal cut as a cylinder with a diameter of
      21.2 mm and a thickness of 5 mm. We achieve 20.5-internal-degree angular tuning
      in a 1064-nm-pumped type III OPO, which would correspond to ~36 degrees external
      angular rotation for a parallelepipedal crystal. The goals of using such a device
      are to narrow the spectral width of the output and to enhance the spatial quality
      of the generated beams in widely tunable OPO's.

PMID- 18064169
TI  - Spectral features associated with nonlinear pulse compression in Bragg gratings.
AB  - We report, for the first time to our knowledge, direct spectral measurements of
      nonlinear spectral broadening caused by nonlinear propagation through Bragg
      gratings written on integrated AlGaAs waveguides. The spectral broadening is
      associated with pulse compression from 400 to 80 ps. The high nonlinearity of
      AlGaAs enables high-repetition-rate, low-peak-power sources to be used,
      facilitating easy spectral measurements.

PMID- 18064170
TI  - Mid-infrared difference-frequency generation in periodically poled KTiOAsO(4) and
      application to gas sensing.
AB  - Tunable mid-infrared radiation (3.45-3.75 microm) with a power level of 0.14
      microW is generated by quasi-phase-matched difference-frequency mixing of a
      Nd:YAG laser and a tunable-diode laser (near 1.5 microm) in multigrating
      periodically poled KTiOAsO(4) . The wavelength and temperature bandwidths are
      approximately 65 nm cm and approximately 62 degrees C, respectively. The
      temperature-tuning slope of the phase-matched idler wavelength, -0.94 nm/ degrees
      C, is almost twice that of periodically poled KTiOPO(4) . We use the measurements
      to derive a mid-infrared-corrected Sellmeier equation for the Z axis of
      KTiOAsO(4). The generated mid-infrared radiation is applied to sensitive high
      resolution spectroscopy of the nu(3) band of methane.

PMID- 18064171
TI  - Mercury thiogallate mid-infrared femtosecond optical parametric generator pumped
      at 1.25 microm by a Cr:forsterite regenerative amplifier.
AB  - We demonstrate a novel traveling-wave-type optical parametric generator based on
      1.25-microm pumping of HgGa(2)S(4) that produces tunable, high-power, transform
      limited infinity 200-fs pulses in the mid-IR from 5 to 9 microm. Output idler
      energies on the microjoule level are obtained with maximum conversion efficiency
      of 11% for the amplifier stage, which is more than two times better than the
      results obtained with an analogous sample of the widely spread material AgGaS(2).

PMID- 18064172
TI  - Bragg-grating-enhanced polarization instabilities.
AB  - Experiments demonstrate a dramatic decrease in polarization-instability threshold
      as an optical pulse is tuned near the short-wavelength edge of the photonic
      bandgap formed by a fiber Bragg grating. These enhanced nonlinear interactions
      and birefringent effects are modeled with coupled-mode numerical simulations.
      Nonlinearities are shown to increase much more rapidly than the effective
      birefringence as the pulse wavelength approaches the bandgap edge.

PMID- 18064173
TI  - Doping of an absorbent into a Raman crystal for suppression of higher-order
      Stokes generation.
AB  - A Raman-active crystal, lanthanum tungstate doped with praseodymium (Pr) ions,
      was grown to facilitate the selection of the order of Stokes waves in stimulated
      Raman scattering. Absorption of the second Stokes wave by the Pr ions suppressed
      conversion to higher-order Stokes waves, resulting in efficient energy conversion
      to the first Stokes wave.

PMID- 18064174
TI  - Adiabatic coupling between conventional dielectric waveguides and waveguides with
      discrete translational symmetry.
AB  - We study adiabatic transformation in optical waveguides with discrete
      translational symmetry. We calculate the reflection and transmission coefficient
      for a structure consisting of a slab waveguide that is adiabatically transformed
      into a photonic crystal waveguide and then back into a slab waveguide. The
      calculation yields high transmission over a wide frequency range of the photonic
      crystal waveguide band and indicates efficient coupling between the slab
      waveguide and the photonic crystal waveguide. Other applications of adiabatic
      mode transformation in photonic crystal waveguides and the coupled-resonator
      optical waveguides are also discussed.

PMID- 18064175
TI  - Influence of hot-carrier luminescence from avalanche photodiodes on time
      correlated photon detection.
AB  - We present the results of our time-resolved measurements of hot-carrier
      luminescence from passively quenched Geiger-mode avalanche photodiodes. In time
      correlated photon-counting (TCPC) experiments, hot-carrier luminescence
      interferes overwhelmingly with the coincidence spectrum, which results in
      artifacts. This potential problem should be taken into account in setting up TCPC
      experiments.

PMID- 18064176
TI  - Nonlinear propagation dynamics of an ultrashort pulse in a hollow waveguide.
AB  - We present a theoretical investigation of the self-focusing dynamics of
      femtosecond pulses in a hollow waveguide. We show that transverse effects play an
      important role in these dynamics, even for pulses that are significantly below
      the critical power for self-focusing in free space, and that excitation of higher
      order modes of the waveguide results in the spreading of the pulse in time.
      Inclusion of self-steepening and space-time focusing in our model is necessary
      for properly capturing the pulse dynamics.

PMID- 18064178
TI  - Vortex streets in walking parametric wave mixing: errata.

PMID- 18064177
TI  - Single-shot measurement of temporal phase shifts by frequency-domain holography.
AB  - Frequency-domain holography is used to measure ultrafast phase shifts induced
      either by the nonlinear susceptibility ?(3) of fused silica or by ionization
      fronts in air over a temporal region of 1 ps with 70-fs resolution in a single
      shot. The use of an imaging spectrometer adds one-dimensional spatial resolution
      to the single-shot temporal measurements.

PMID- 18064179
TI  - Adaptive wave-front correction by means of all-optical feedback interferometry.
AB  - A novel adaptive wave-front correction system based on an all-optical feedback
      interferometer is described. In this system the two-dimensional output fringe
      intensity from a Mach-Zehnder interferometer with large radial shear is optically
      fed back to an optically addressed phase-only liquid-crystal spatial light
      modulator. Consequently, without a separate aberration-free reference wave, the
      modulator phase approximates the conjugate of the interferometer phase that is
      directly related to the phase of the input aberrated wave front, so this system
      is applicable in adaptive optics. We successfully achieved real-time correction
      of aberrated wave fronts: A diffraction pattern that was seriously distorted
      because of aberrations was transformed into a diffraction-limited spot
      immediately after the feedback loop was closed.

PMID- 18064180
TI  - Apochromatic optical correlation.
AB  - Optical correlation, or matched filtering, can now be applied more widely than
      before, because the light is now allowed to be totally incoherent, spatially and
      spectrally. Two such correlators were demonstrated recently. Their state of
      chromatic correction can be called achromatic, since the scaling error has two
      zero crossings within the visible range of wavelengths. We present a new
      apochromatic correlator, in which the scaling error has three zero crossings. The
      maximum error and the rms error are reduced by a factor of 5. Our apochromatic
      correlator is composed of two highly dispersive heavy flint lenses that are in
      contact with two diffractive lenses and two chromatic corrected refractive
      lenses. The uncommon combination of flint dispersion and diffractive dispersion
      enabled us to achieve apochromatic correction of the scaling factor of the
      correlator.

PMID- 18064181
TI  - Inhibited emission in photonic woodpile lattices.
AB  - The emission and transmission properties of realistic photonic-band-structure
      woodpile lattices are investigated by use of a scattering-matrix treatment.
      Lattices with three to nine layers are studied, and the results are interpreted
      with band-structure calculations for an infinite lattice. Calculations of the
      total radiative loss rate for a source within the lattice show that these
      structures can provide significant inhibition of emission, with values as low as
      3% of the free-space value in the nine-layer structure.

PMID- 18064182
TI  - Near-field distributions of resonant modes in small dielectric objects on flat
      surfaces.
AB  - We report numerical simulations of the coupling of waves, either propagating or
      evanescent, with the eigenmodes of dielectric nanocylinders and nanospheres upon
      substrates. The multiple interaction of light between these objects and the
      dielectric surface at which the evanescent waves are created is taken into
      account. In this way, we present an accurate procedure for predicting and
      controlling the creation of large field enhancements concentrated both within and
      near the nanoparticle compared with the angle of incidence and the state of
      polarization.

PMID- 18064183
TI  - Paraxial-domain diffractive elements with 100% efficiency based on polarization
      gratings.
AB  - The concept of polarization freedom is employed to design diffraction gratings
      that are capable of transforming an electromagnetic plane wave into two or three
      diffraction orders with an arbitrary efficiency distribution among them, such
      that the combined efficiency of the signal orders is always equal to 100%. As a
      special case we consider paraxial-domain duplicators and triplicators with 100%
      efficiency, which is not possible for illumination by scalar waves: Diffractive
      elements that are capable of performing the required wave transformation must
      modulate the state of polarization of the incident field.

PMID- 18064184
TI  - Simple grating synthesis algorithm.
AB  - Many authors (including this one) have suggested that the problem of synthesizing
      a grating from its reflection spectrum is significantly more difficult than the
      direct problem of obtaining the spectrum from the grating. Fortunately, this view
      is mistaken. One can synthesize a grating from any reflection spectrum by direct
      solution of the standard coupled-mode equations while simultaneously evaluating a
      simple integral to obtain the grating strength. This approach has the advantage
      of being based on a well-understood set of equations, making it amenable to
      physical interpretation, mathematical approximation, and generalization.

PMID- 18064185
TI  - Nearly zero ultraflattened dispersion in photonic crystal fibers.
AB  - We present a procedure for achieving photonic crystal fibers with nearly zero
      ultraflattened group-velocity dispersion. Systematic knowledge of the special
      guiding properties of these fibers permits the achievement of qualitatively novel
      dispersion curves. Unlike the behavior of conventional fibers, this new type of
      dispersion behavior permits remarkably improved suppression of third-order
      dispersion, particularly in the low-dispersion domain.

PMID- 18064186
TI  - Recovered efficiency of filter control in dispersion-managed solitons for optical
      regeneration applications: analysis and experimental validation.
AB  - We demonstrate numerically that local conversion of dispersion-managed return-to
      zero pulses into nonlinear Schrodinger solitons fully restores optical filtering
      control for energy stabilization, thus permitting the association of optical
      regeneration with dispersion-managed propagation. Experimental validation is
      achieved by means of 40-Gbit/s regenerated dispersion-managed loop transmission
      over 10,000 km.

PMID- 18064187
TI  - Optical properties of high-delta air silica microstructure optical fibers.
AB  - We analyze the waveguide properties of microstructure optical fibers consisting
      of a silica core surrounded by a single ring of large air holes. Although the
      fibers can support numerous transverse spatial modes, coupling between these
      modes even in the presence of large perturbations is prevented for small core
      dimensions, owing to a large wave-vector mismatch between the lowest-order modes.
      The result is an optical fiber that can appear single mode with propagation
      properties that can be achieved only in multimode waveguides.

PMID- 18064188
TI  - Optoelectronic delay-time controller for laser pulses.
AB  - A dc-voltage-controlled optoelectronic delay line for continuous tuning of the
      relative delay time of an optical pulse train generated from a gain-switched
      laser diode is demonstrated. A maximum tunable range delay time of 3.9 ns (
      approximately 2 periods) for optical pulses at a 500-MHz repetition rate is
      reported, which corresponds to a phase shift of as much as 4pi. The tuning
      responsivity and resolution of the current apparatus are 0.54 ps/mV and <0.2 ps,
      respectively. The measured timing fluctuation and long-term drift at any delay
      time are 0.13 ps and 20 fs/min, respectively. This scheme further permits the
      simultaneous phase tracking of the laser pulse train to unknown signals generated
      from the device under test.

PMID- 18064189
TI  - Optimization of retardance for a complete Stokes polarimeter.
AB  - We present two figures of merit based on singular value decomposition, which can
      be used to assess the noise immunity of a complete Stokes polarimeter. These are
      used to optimize a polarimeter featuring a rotatable retarder and a fixed
      polarizer. A retardance of 132 degrees (approximately three-eighths wave) and
      retarder orientation angles of +/-51.7 degrees and +/-15.1 degrees are found to
      be optimal when four measurements are used. Use of this retardance affords a
      factor-of-1.5 improvement in signal-to-noise ratio over systems employing a
      quarter-wave plate. A geometric means of visualizing the optimization process is
      discussed, and the advantages of the use of additional measurements are
      investigated. No advantage of using retarder orientation angles spaced uniformly
      through 360 degrees is found over repeated measurements made at the four retarder
      orientation angles.

PMID- 18064190
TI  - High-power dual-rod Yb:YAG laser.
AB  - We describe a diode-pumped Yb:YAG laser that produces 1080 W of power cw with
      27.5% optical optical efficiency and 532 W Q-switched with M(2)=2.2 and 17%
      optical-optical efficiency. The laser uses two composite Yb:YAG rods separated by
      a 90 degrees quartz rotator for bifocusing compensation. A microlensed diode
      array end pumps each rod, using a hollow lens duct for pump delivery. By changing
      resonator parameters we can adjust the fundamental mode size and the output beam
      quality. Using a flattened Gaussian intensity profile to calculate the mode-fill
      efficiency and clipping losses, we compare experimental data with modeled output
      power versus beam quality.

PMID- 18064191
TI  - Experimental demonstration of suppression of low-frequency fluctuations and
      stabilization of an external-cavity laser diode.
AB  - We demonstrate experimentally all-optical stabilization of a single-mode laser
      diode subject to external optical feedback operating in the low-frequency
      fluctuations (LFF) regime, by the technique of applying a second delayed optical
      feedback. We interpret our results as suppression of LFF through destruction of
      the antimodes responsible for the LFF crises and stabilization of the laser
      through creation of new maximum gain modes, in agreement with recent theoretical
      predictions.

PMID- 18064192
TI  - Enhanced excess noise in laser cavities with tilted mirrors.
AB  - Enhancement of the transverse excess-noise factor is theoretically predicted in
      optical laser cavities with tilted end mirrors and nonuniform transverse loss. In
      particular, it is shown that in a loss-guided laser close to the plane-plane
      geometric instability boundary the excess-noise factor that is induced by mirror
      tilting may largely exceed that predicted for the aligned cavity. This excess
      noise is related to beam walk-off induced by mirror tilting, which makes possible
      transient amplification of noise in the transverse plane.

PMID- 18064193
TI  - Spatial structure of broad-area vertical-cavity regenerative amplifiers.
AB  - We investigate the spatial structure of broad-area vertical-cavity regenerative
      amplifiers injected with a homogeneous beam. The emerging patterns have a
      predominantly sixfold rotational symmetry, verifying the recent prediction of
      formation of hexagons. The length scale is controllable by means of detuning and
      follows the prediction for tilted waves.

PMID- 18064194
TI  - Improved emission of Tm(3+)-doped glass for a 1.4-mum amplifier by radiative
      energy transfer between Tm(3+) and Nd(3+).
AB  - We prepared a Tm-doped glass composite with a Nd-doped layer as a model 1.4-mum
      thulium-doped fiber amplifier (TDFA) to investigate the effect of energy transfer
      on the emission spectra of the composite. The competitive 0.8-mu;m emission from
      the Tm:(3)H(4) level, which had a branching ratio ten times larger than that of
      the 1.4-mum emission, was reduced to 1/6 of its previous value by radiative
      transfer to the Nd layer. Also, the 1.06-mum emission from the excited Nd(3+) was
      found to contribute to the upconversion pumping scheme for population inversion
      between the (3)i(4) and (3)F(4) levels of Tm(3+) . The Nd-doped glass phase can
      be used as a cladding material for an efficient TDFA.

PMID- 18064195
TI  - Spectral measurement of absorption by spectroscopic frequency-domain optical
      coherence tomography.
AB  - A new method of measurement that essentially combines Fourier-domain optical
      coherence tomography with spectroscopy is introduced. By use of a windowed
      Fourier transform it is possible to obtain, in addition to the object structure,
      spectroscopic information such as the absorption properties of materials. The
      feasibility of this new method for performing depth-resolved spectroscopy is
      demonstrated with a glass filter plate. The results are compared with
      theoretically calculated spectra by use of the well-known spectral
      characteristics of the light source and the filter plate.

PMID- 18064196
TI  - Optical V(z) for high-resolution 2pi surface plasmon microscopy.
AB  - Surface plasmons are electromagnetic surface waves whose k vectors are greater
      than that of free-space radiation. We excite surface plasmons by using an oil
      immersion lens, which forms one arm of an interferometer. We demonstrate the way
      in which the characteristic output variation with defocus is determined by the
      propagation properties of the surface plasmons, which leads to diffraction
      limited surface plasmon microscopy in the far field.

PMID- 18064197
TI  - Coherence enhancement of spatially incoherent light beams through soliton
      interactions.
AB  - We show that the spatial coherence of a partially incoherent light beam can be
      greatly enhanced through an energy-conserving interaction with an incoherent or a
      coherent dark spatial soliton. Computer simulations show that during this process
      a portion of the incoherent beam is trapped within the dark notch of the dark
      soliton, thus forming a sharp intensity spike. In this region the correlation
      length dramatically increases by at least 2 orders of magnitude.

PMID- 18064198
TI  - Cascaded highly nondegenerate four-wave-mixing phenomenon in transparent
      isotropic condensed media.
AB  - Broad-bandwidth light pulses with different frequencies, extending from the IR to
      the UV, are simultaneously generated when two noncollinear, ultrafast laser
      pulses from a visible dual-frequency laser propagate through bulk isotropic
      transparent media such as common glass. This phenomenon, which is believed to
      have been previously unreported, can be explained by a cascade of highly
      nondegenerate four-wave-mixing processes and corresponds to a coherent scattering
      effect with geometrically minimized phase mismatch. Frequency-upconverted beams
      were observed up to the 11th order.

PMID- 18064199
TI  - Simultaneous optical wavelength interchange with a two-dimensional second-order
      nonlinear photonic crystal.
AB  - We present a theoretical analysis for simultaneous optical wavelength interchange
      and isolation of a pair of collinear input optical signals by use of two
      concurrent difference-frequency-generation processes in a two-dimensional second
      order nonlinear photonic crystal. We have derived a set of relations, including a
      general nonlinear Bragg condition, that we use to determine the parameters of the
      nonlinear lattice, given the input wavelengths and desired exit angles of the
      wavelength-interchanged outputs.

PMID- 18064200
TI  - Near-field second-harmonic microscopy of thin ferroelectric films.
AB  - We present a near-field optical technique for second-harmonic imaging by use of
      tapered optical fiber tips externally illuminated with femtosecond laser pulses.
      Enhancement of the electric field at the tip of the fiber results in enhanced
      second-harmonic (SH) generation from the sample region near the tip. This SH
      emission is collected by the same tapered fiber. The spatial distribution and
      polarization properties of SH generation from thin ferroelectric films and a
      poled single crystal of BaTiO(3) have been studied. A spatial resolution of the
      order of 80 nm was achieved. Symmetry properties of the near-field SH signal
      allow us to recover the local poling direction of individual ferroelectric
      domains in the film. Thus the technique provides a novel tool for nanometer-scale
      crystal analysis of polycrystalline samples.

PMID- 18064201
TI  - Optical limitation in resonant Faraday media.
AB  - Optical limitation in resonant Faraday media sandwiched between crossed
      polarizers is analyzed both theoretically and experimentally. In this technique
      resonant Faraday rotation permits a net transmission at low intensity levels,
      whereas the setup transmission is quenched at higher intensities when the active
      transition is completely saturated. This technique offers many advantages, such
      as a very low fluence threshold (~12 nJ/cm(2) in cesium vapor), a high intensity
      range (more than 4 orders of magnitude for polarizer losses of 10(-5)), and quasi
      invulnerability to optical damage, which make this technique attractive for the
      protection of fixed-wavelength operated detectors.

PMID- 18064202
TI  - ZnGeP2 optical parametric oscillator with 3.8-12.4-mum tunability.
AB  - A ZnGeP>(2) (ZGP) optical parametric oscillator (OPO) with wide mid-IR tunability
      has been demonstrated. The singly resonant angle-tuned ZGP OPO was pumped by 100
      ns erbium laser pulses at lambda =2.93mum and yielded output that was
      continuously tunable from 3.8 to 12.4 mum (type I phase matching) and from 4 to
      10 mum (type II phase matching). An OPO pump threshold was less than 1 mJ in the
      whole 4-12 mum range of the output, and the quantum conversion efficiency reached
      35%. An OPO linewidth was typically a few wave numbers; however, with a single
      intracavity etalon (uncoated Si plate) in a type II OPO it was narrowed to
      <0.5cm(-1). We demonstrate the sensitive detection of N(2)O gas with the narrow
      linewidth OPO.

PMID- 18064203
TI  - Experimental observation of plasmon polariton waves supported by a thin metal
      film of finite width.
AB  - What are believed to be the first experimental observations of the existence of
      long-range plasmon-polariton waves, guided by a thin metal film of finite width,
      are presented. A waveguide composed of an 8-mum-wide, 20-nm-thick, 3.5-mm-long Au
      metal film embedded in SiO (2) was successfully excited at a free-space
      wavelength of 1.55 mum in an end-fire experiment. The theoretical nature of the
      phenomenon is described, and experimental observations of field confinement
      provided by this metal waveguide are presented in detail.

PMID- 18064204
TI  - Enhanced nonlinearity and transparency via autoionizing resonance.
AB  - The nonlinear response of an autoionizing medium in which coherence is
      established essentially by nonradiative interactions is analyzed. It is found
      that, by proper tuning of two radiation fields, the third-order nonlinearities
      can be enhanced while the absorption is canceled. The proposed scheme is
      particularly useful for enhancing nonlinearities in the VUV region.

PMID- 18064205
TI  - Chirp control in the direct space-to-time pulse shaper.
AB  - The dispersion properties of the direct space-to-time pulse shaper are
      investigated for the first time to our knowledge. We demonstrate that phase-front
      curvature of the input spatial profile leads to a chirp in the output temporal
      waveform, which one can compensate for by varying the separation between the
      pulse-shaping lens and slit. Furthermore, the output intensity profile remains
      invariant as the chirp is manipulated. These properties are fundamentally
      different than in the well-known Fourier-transform pulse shaper.

PMID- 18064206
TI  - Diffractive optics implementation of six-wave mixing.
AB  - Diffractive optics are applied to six-wave mixing processes to provide a single
      optic approach to attaining the required, relatively complex, phase-matching
      geometry to discriminate against lower-order nonlinear responses. The diffractive
      optics were designed specifically for broad-bandwidth operation and passive phase
      locking of the appropriate pulse pairs for use in femtosecond two-dimensional
      Raman studies of the dynamic structure of liquids. The fifth-order signal was
      studied in liquid CS>(2); two different colors were used for the excitation and
      the probe to reduce background scatter, as were two different phase-matching
      geometries with different degrees of suppression of cascaded third-order
      processes.

PMID- 18064207
TI  - Measurement of the optical phase relation among subharmonic pulses in a
      femtosecond optical parametric oscillator.
AB  - We observed the phase relation among subharmonic pulses generated by a
      femtosecond optical parametric oscillator (OPO). The ratio of the optical
      frequencies of the idler, the signal, and the pump pulses was set to 1:2:3. Under
      these conditions the wavelengths of the second harmonic of the signal pulse and
      the sum frequency between the pump and the idler pulses are the same. The beat
      signal between these two pulses represents the phase relationship among the pump,
      the signal, and the idler. The beat frequency varied when the cavity length of
      the OPO was changed.

PMID- 18064209
TI  - Interfacial shape and contact-angle measurement of transparent samples with
      confocal interference microscopy: a publisher's erratum.

PMID- 18064210
TI  - Nonparaxial propagation of a cylindrical beam with Lanczos reduction.
AB  - We discuss a numerical method based on Lanczos reduction of modeling nonparaxial
      propagation of a cylindrical symmetric beam. To illustrate the performance and
      demonstrate the significant difference between nonparaxial and paraxial beams, we
      consider Gaussian beam propagation in two different settings.

PMID- 18064208
TI  - 16.2-W average power from a diode-pumped femtosecond Yb:YAG thin disk laser.
AB  - We demonstrate a power-scalable concept for high-power all-solid-state
      femtosecond lasers, based on passive mode locking of Yb:YAG thin disk lasers with
      semiconductor saturable-absorber mirrors. We obtained 16.2 W of average output
      power in pulses with 730-fs duration, 0.47-muJ pulse energy, and 560-kW peak
      power. This is to our knowledge the highest average power reported for a laser
      oscillator in the subpicosecond regime. Single-pass frequency doubling through a
      5-mm-long lithium triborate crystal (LBO) yields 8-W average output power of 515
      nm radiation.

PMID- 18064211
TI  - Contribution of photoinduced densification to refractive-index modulation in
      Bragg gratings written in Ge-doped silica fibers.
AB  - We have computed the contribution of UV-light-induced densification to the
      refractive-index modulation of fiber Bragg gratings. Our results confirm that,
      for strong gratings written in Ge-doped silica fibers with 248-nm UV light,
      density changes account for a major part of the photosensitivity effect.

PMID- 18064212
TI  - Statistical determination of the length dependence of high-order polarization
      mode dispersion.
AB  - We describe a method of characterizing high-order polarization mode dispersion
      (PMD). Using a new expansion to approximate the Jones matrix of a polarization
      dispersive medium, we study the length dependence of high-order PMD to the fourth
      order. A simple rule for the asymptotic behavior of PMD for short and long fibers
      is found. It is also shown that, in long fibers (~1000 km), at 40 Gbits/s the
      third- and fourth-order PMD may become comparable to the second-order PMD.

PMID- 18064213
TI  - Optical all-pass filters for polarization mode dispersion compensation.
AB  - Polarization mode dispersion (PMD) compensation is addressed by decomposition of
      a fiber's Jones matrix into amplitude and phase responses, which are then
      compensated for separately. Cubic and higher-order phase compensation
      substantially reduce the cumulative probability at a given system penalty over
      first-order PMD compensation, as demonstrated for a 40-Gbit/s non-return-to-zero
      signal and a fiber PMD with a differential group delay of 20 ps (rms). Single
      stage all-pass filters provide tunable compensation that is comparable to that
      obtained with a variable-delay line, and multistage all-pass filters are well
      suited for higher-order phase compensation.

PMID- 18064214
TI  - Spectral domain analysis of dispersion management without averaging.
AB  - It is shown how a straightforward regular perturbative analysis can be used to
      derive an integral equation for the spectral shape of a dispersion-managed
      soliton that takes fiber loss and amplification into account without resorting to
      averaging. Using functional analysis, one can then find an accurate approximate
      Gaussian solution that should prove useful for the design of a dispersion-managed
      transmission link.

PMID- 18064215
TI  - Anomalous pulse-width narrowing with first-order compensation of polarization
      mode dispersion.
AB  - We present analytical and experimental results to demonstrate the narrowing of
      pulses transmitted through optical fibers, with polarization mode dispersion
      compensated for to first order in frequency. The compensation technique splits
      the optical signal at the fiber output into polarization components that are
      aligned with the output principal states of polarization, and only one of the two
      components is subsequently detected. It is shown that it is possible with this
      compensation technique to have output pulses that are narrower than the input
      pulses. Pulse narrowing can also be found when the optical signal is split into
      orthogonal polarization components that are not principal states of polarization.

PMID- 18064216
TI  - Optical encryption by double-random phase encoding in the fractional Fourier
      domain.
AB  - We propose an optical architecture that encodes a primary image to stationary
      white noise by using two statistically independent random phase codes. The
      encoding is done in the fractional Fourier domain. The optical distribution in
      any two planes of a quadratic phase system (QPS) are related by fractional
      Fourier transform of the appropriately scaled distribution in the two input
      planes. Thus a QPS offers a continuum of planes in which encoding can be done.
      The six parameters that characterize the QPS in addition to the random phase
      codes form the key to the encrypted image. The proposed method has an enhanced
      security value compared with earlier methods. Experimental results in support of
      the proposed idea are presented.

PMID- 18064218
TI  - Prism interferometer for a compact Fourier-transform spectroscope.
AB  - As a step toward a field-use spectrometer based on Fourier-transform
      spectroscopy, we have developed a prism-scanning interferometer. It consists of a
      sliding triangular prism with two mirror surfaces attached to a fixed triangular
      prism beam splitter. This design eliminates the effect of ambient air and
      simplifies alignment, which can otherwise be time consuming. It also halves the
      stage-moving distance, because the optical path difference is doubled, since both
      mirrors move while the sliding prism is scanning. We have tested the basic
      operation of the prototype and found that the spectral resolution and the
      wavelength scale agree well with our simple calculation.

PMID- 18064217
TI  - Real-time holograms generated by second-harmonic cross correlation of object and
      reference optical wave fields.
AB  - Three-dimensional holographic images of extended diffusing objects are
      simultaneously recorded and reconstructed by optical cross correlation in a
      second-order nonlinear crystal. An interaction geometry in which the phase
      matched object and reference fields propagate slightly noncollinearly is
      particularly convenient for producing these second-harmonic-generated holograms.

PMID- 18064219
TI  - Existence of two coupling constants in microchip lasers.
AB  - We implemented two different experimental setups to probe directly the nonlinear
      coupling between modes in microchip lasers. We show that, remarkably, the results
      can be interpreted by use of Lamb's coupling constant. In an Er, Yb:glass
      microchip laser, we measured C(12) = 0.80 between longitudinal modes and C(xy) =
      0.95 between orthogonally linearly polarized eigenstates. The high values
      obtained give some physical insight into the single-frequency operation of such
      lasers.

PMID- 18064220
TI  - Amplitude-modulation-free optoelectronic frequency control of laser diodes.
AB  - A novel method is described for fast frequency modulation or frequency control of
      diode lasers that avoids problems associated with bias current modulation,
      namely, amplitude modulation and thermal phase delays. The method is based on
      amplitude-modulated, noninterfering control light with a wavelength near the
      transparency region of the laser diode, which specifically modifies the spectral
      gain profile to yield a constant gain but a controllable refractive index at the
      lasing wavelength. This permits amplitude-modulation-free frequency modulation at
      modulation frequencies up to the relaxation oscillation frequency. A phase lock
      between the emissions of two extended-cavity diode lasers that could not be
      achieved with bias current modulation was achieved by this method.

PMID- 18064221
TI  - Enhanced photoinduced chi((2)) in gamma-ray-irradiated bulk glass.
AB  - Gamma-ray-irradiated light-flint silicate bulk glass (Schott Glass LF5), which
      contains a large amount of lead oxide, displays enhanced photoinduced quasi-phase
      matched second-harmonic generation (PSHG), whereas nonirradiated glass under the
      same experimental conditions does not generate this nonlinear effect. The
      dependence of the efficiency of PSHG on the amount of gamma radiation (up to 530
      krad) is experimentally studied, as is the role of thermal recovery (bleaching)
      of the color centers as a result of seeding with the second harmonic. The effect
      of long-term fading is studied with a sample that was irradiated 8 years ago.
      Gamma irradiation of boron-crown silicate glass (BK7) does not show this
      enhancement.

PMID- 18064222
TI  - Frequency stabilization of a frequency-doubled 1556-nm source to the 5S(1/2) ? 5D
      (5/2) two-photon transitions of rubidium.
AB  - Improvements in the power level of sources near 1550 nm and in the efficiency of
      waveguide frequency doublers enabled us to lock a frequency-doubled source
      directly to the 5S(1/2) ? 5D(5/2) two-photon transitions near 778 nm. We obtained
      a sufficiently powerful second-harmonic signal, exceeding 2 mW, by doubling an
      external-cavity diode laser that was amplified by an erbium-doped fiber amplifier
      in a periodically poled LiNbO(3) channel waveguide. Our experimental scheme can
      be used for realizing compact, high-performance frequency standards near 1550 nm
      for fiber-optic communication and sensing applications.

PMID- 18064223
TI  - Nonvolatile photorefractive holograms in LiNbO(3):CuCe crystals.
AB  - We report experimental and theoretical studies of nonvolatile photorefractive
      holographic recording in LiNbO(3):Cu:Ce crystals with two illumination schemes:
      (1) UV light for sensitization and a red interfering pattern for recording and
      (2) blue light for sensitization and a red pattern for recording. The results
      show that the oxidized LiNbO(3):Cu:Ce crystals can provide high, persistent
      refractive-index modulation with weak light-induced scattering. The optimal
      working conditions and the prescription for doping and oxidation-reduction
      processing that yields the maximum refractive-index modulation are discussed.

PMID- 18064224
TI  - Far-infrared properties of DAST.
AB  - Using terahertz time-domain spectroscopy, we have measured the index of
      refraction and the absorption coefficient of the organic ionic salt 4-N, N
      dimethylamino-4?-N?-methyl-stilbazolium tosylate (DAST). This promising organic
      electro-optic material exhibits strong absorption and dispersion for frequencies
      above 1 THz at both room temperature and 83 K. No reduction in the absorption
      strength is observed when DAST is cooled, suggesting a single-phonon origin of
      the resonances. A simple vibration of the anion and cation of the salt is
      suggested as the origin of the exceptionally strong far-infrared absorption and
      the high-frequency electro-optic properties of DAST.

PMID- 18064225
TI  - Measurements of the thickness distribution of thin films with a slit-beam-profile
      reflectometer.
AB  - The thickness distribution of single-layer thin films is measured with a slit
      beam-profile reflectometer. A convergent slit beam generated by a cylindrical
      lens is projected onto a specimen. A CCD chip with a pixel matrix of 512 x 480 is
      used to detect the intensity distribution of the reflected beam, which is passed
      through another cylindrical lens. By analyzing the picture taken by the CCD, we
      can obtain information about the angular reflectance at each reflecting point
      along the slit line, and the thickness or the refractive index at each point can
      be evaluated by mathematical fitting to a reflectance formula.

PMID- 18064226
TI  - Temporal coherent control of a sequential transition in rubidium atoms.
AB  - An experimental investigation of the coherent interaction of femtosecond pulses
      with two resonant sequential transitions of Rb atoms is presented. Fluorescence
      from the atomic system exhibits beating at a frequency given by difference in the
      sequential atomic transitions. The results are interpreted in terms of quantum
      interference in the induced coherence and its interaction with the field that
      results from a cooperative emission process.

PMID- 18064228
TI  - Photon statistics of laserlike emission from polymeric scattering gain media.
AB  - The coherent properties of the temporally and spectrally narrowed emission of
      laser-induced fluorescence of organic dyes hosted inside artificial scattering
      matrices (random lasers) were investigated. The excitation source was a frequency
      doubled 200-fs pulsed laser emitting at 400 nm. Spectral and temporal features
      were simultaneously recorded with a spectrograph and a streak camera operating in
      photon-counting mode. Photon-number distributions were thus created. The temporal
      coherence of the laserlike emission above and below the excitation energy
      threshold was investigated from the photon-number distribution that was obtained.

PMID- 18064227
TI  - Frequency-switched heterodyne cavity ringdown spectroscopy.
AB  - When the frequency of light coupled into a cavity is suddenly shifted, the
      radiation emanating from the input port of the previously excited cavity can beat
      with the reflection of the frequency-shifted input on the surface of a
      photodetector. When the beat frequency is stable, the time decay of the resulting
      optical heterodyne signal can be used to measure intracavity absorption spectra
      with near quantum-limited sensitivity.

PMID- 18064229
TI  - Time-dependent scattering of a standing surface plasmon by rapid ionization in a
      semiconductor.
AB  - Scattering of a standing surface plasmon by rapid ionization in a semiconductor
      is investigated. We show that, for a standing plasmon, in contrast with a
      traveling plasmon, the scattering depends on the plasmon phase at the moment of
      ionization. By changing the moment of ionization, we can control the energy that
      is transferred into newly excited modes, which include a frequency-upshifted
      standing surface plasmon, transient outgoing radiation, and free-streaming
      currents with a static magnetic field in the semiconductor. The phenomena that
      are described open new possibilities for probing the dynamics of surface
      excitations in semiconductors on an ultrashort time scale.

PMID- 18064230
TI  - Real-time two-dimensional imaging in scattering media by use of a femtosecond
      Cr(4+):forsterite laser.
AB  - An original femtosecond Cr(4+):forsterite laser source associated with a
      nonlinear optical correlator was used for imaging through scattering media with
      1220-nm light. The system, which operates as an ultrafast optical gate by sum
      frequency generation in a nonlinear crystal, was able to detect the light
      reflected from a resolution chart hidden in a turbid medium, at an attenuation of
      as much as 15 mean free paths. When the object was illuminated with a collimated
      beam, real-time two-dimensional images were obtained, with a maximum transverse
      resolution of ~20 microm.

PMID- 18064231
TI  - Ultraviolet-initiated reactions of H(2) with germanosilicate fibers and H(2)
      concentration dependence of the Bragg wavelength of a fiber grating: errata.

PMID- 18064232
TI  - Polarized light propagation through tissue phantoms containing densely packed
      scatterers: errata.

PMID- 18064233
TI  - Continuous-phase elements can improve laser beam quality.
AB  - Siegman [Opt. Lett. 18, 675 (1993)] showed that binary-phase plates cannot
      improve laser beam quality. We demonstrate that continuous spiral phase elements
      can improve the quality of beams that originate from a laser operating with a
      pure high-order transverse mode. A theoretical analysis is presented, along with
      experimental results obtained with a CO(2) laser. The results reveal that a
      nearly optimal Gaussian output beam can be obtained with only a small decrease in
      the output power.

PMID- 18064234
TI  - Two-dimensional photonic crystal couplers for unidirectional light output.
AB  - We investigate the use of two-dimensional photonic crystal slabs to improve the
      directionality of output coupling from planar waveguides and distributed-feedback
      lasers. We present the theory underlying the operation of such structures and
      design criteria for emission in desired directions. As an example, we demonstrate
      a vertical coupler that is integrated with an organic distributed-feedback laser,
      use computer simulations to find its coupling constant and efficiency, and then
      discuss its feasibility.

PMID- 18064235
TI  - Coherent transient data-rate conversion and data transformation.
AB  - Temporal compressions of optical pulses and pulse trains have been performed by
      the photon-echo process in Tm-doped YAG at 793 nm. Single-pulse temporal
      compression by almost a factor of 500 from 10 micros to 22 ns and pulse train
      compression by a factor of 14 from 5micros to 350 ns with a high-speed frequency
      tunable external-cavity diode laser are demonstrated. It is suspected that
      significantly higher compression could be obtained by improved control of the
      laser frequency and laser frequency chirps. Theoretically, Tm-doped YAG should be
      capable of compressing single pulses by almost a factor of 10(7).

PMID- 18064236
TI  - Stabilization of an active harmonically mode-locked fiber laser using two-photon
      absorption.
AB  - Two-photon absorption provided by a semiconductor mirror structure is shown to
      reduce amplitude fluctuations significantly in a harmonically mo e-locked fiber
      ring laser. Pulse dropouts are eliminated in a laser that produces picosecond
      pulses at a repetition rate of 2 GHz.

PMID- 18064238
TI  - Fiber-coupled multiplexed confocal microscope.
AB  - We describe a new parallel scanning mechanism for confocal microscopy that is
      inherently fiber-optic compatible and that retains the simplicity of the line
      scanning confocal microscope. The method works by employing an incoherent fiber
      optic bundle that maps a line illumination pattern back on itself on double
      passing, while separating the fibers that carry photons from out-of-focus sample
      planes. The transformation permits efficient rejection of out-of-focus photons by
      a slit aperture.

PMID- 18064237
TI  - Quantification by random walk of the optical parameters of nonlocalized
      abnormalities embedded within tissuelike phantoms.
AB  - We have extended a random-walk theory that uses time-dependent contrast functions
      to quantify the cross section and the corrected scattering and absorption
      coefficients of abnormal nonlocalized targets from time-of-flight (TOF) data
      obtained in time-resolved transillumination experiments. Experimental TOF's are
      used to show that this newly developed random-walk method is able to quantify the
      size and the optical properties of embedded nonlocalized targets in with an error
      rate of </=25%.

PMID- 18064239
TI  - Vectorial Kerr-cavity solitons.
AB  - It is shown that a Kerr cavity with different losses for the two polarization
      components of the field can support both dark and bright cavity solitons (CS's).
      A parametrically driven Ginzburg-Landau equation is shown to describe the system
      for large-cavity anisotropy. In one transverse dimension the nonlinear dynamics
      of the bright CS's is numerically investigated.

PMID- 18064240
TI  - Real-time monitoring of all-optical poling of azo-dye polymer thin film.
AB  - Simultaneous writing and probing of photoinduced second-order susceptibility
      chi((2)) in an azo-dye polymer thin film is demonstrated. The method is based on
      the fact that tensor properties of chi((2)) provide different planes of
      polarization for seeding and signal second harmonics. Our technique allows the
      chi((2)) value to be monitored in real time, completely eliminating the
      distortion of optical poling that can occur in traditional probing
      configurations. The possibility of attaining high values of chi((2)) in a DR1
      PMMA guest?host system under low seeding intensities is shown.

PMID- 18064241
TI  - Soliton electro-optic effects in paraelectrics.
AB  - The combination of charge separation induced by the formation of a single
      photorefractive screening soliton and an applied external bias field in a
      paraelectric is shown to lead to a family of useful electro-optic guiding
      patterns and properties.

PMID- 18064242
TI  - Cascading phase shift and multivalued response in counterpropagating frequency
      nondegenerate parametric amplifiers.
AB  - We propose and analyze a novel geometry for all-optical processing of low-power
      signals that is based on a frequency-nondegenerate counterpropagating parametric
      amplifier. The stationary response in the cascading regime exhibits multivalued
      solutions with enhanced nonlinear phase shifts. Implementation in a quasi-phase
      matched LiNbO(3) waveguide is discussed.

PMID- 18064243
TI  - Singly resonant optical parametric oscillator in periodically poled KTiOPO(4)
      pumped by a Bessel beam.
AB  - Conical pumping was used in a periodically poled KTiOPO(4) optical parametric
      oscillator for singly resonant idler generation in a nearly diffraction-limited
      axial beam. A single signal-idler pair was generated over the whole tuning range
      by use of asymmetric reflectivity of the OPO mirrors. Pump depletion of 40% and
      total conversion efficiency of 27% were obtained. Additional OPO tuning
      capability was demonstrated by adjustment of the angle of the conical pump beam.

PMID- 18064244
TI  - Elliptic incoherent solitons in saturable nonlinear media.
AB  - We identify elliptic incoherent spatial solitons in isotropic saturable nonlinear
      media. These solitary states are possible, provided that their correlation
      function is anisotropic. The propagation dynamics of this new class of solitons
      are investigated by use of numerical simulations. We find that, during a
      collision event of two such elliptic solitons, their intensity ellipse rotates,
      and at the same time their centers of gravity tend to revolve around each other.

PMID- 18064245
TI  - Characterization of a polymer microlens fabricated by use of the hydrophobic
      effect.
AB  - We report a means of fabricating hydrophilic domains in a hydrophobic background
      by lithographically patterning an adhesive hydrophobic layer. Polymer microlenses
      were fabricated on these substrates by use of a dip-coating technique. Various
      lens shapes (circular, elliptical, square) were fabricated on a variety of
      substrates (SiO(2), SiN, GaAs, InP, etc.), ranging in size from 2 to 500 microm
      in diameter, with fill factors of up to 90%. Plano-convex and double-convex
      lenses were fabricated, with f-numbers as low as 1.38 and 1.2, respectively.
      Optimum lens surfaces deviated from spherical by just +/-5 nm . The lenses are
      stable at room temperature and exhibit minimal degradation after 24 h at 105
      degrees C. The transfer of these polymer lenses to an underlying substrate was
      also demonstrated.

PMID- 18064246
TI  - All-optical image processing with a supranonlinear dye-doped liquid-crystal film.
AB  - We demonstrate a dynamic all-optical image-intensity-inversion technique that
      uses self- and mutual-phase-modulation effects with a highly nonlinear nematic
      liquid-crystal film placed in an intermediate focal plane. This process requires
      submilliwatt optical power, responds in a few milliseconds, and can be realized
      over a very broad spectral range.

PMID- 18064247
TI  - Generation of femtosecond Bessel beams with microaxicon arrays.
AB  - Multiple quasi-Bessel beams are generated by transmission of sub-30-fs pulses
      from a Ti:sapphire laser through refractive thin-film microaxicon arrays. Time
      integrated intensity distributions at several axial positions and for pulse
      durations of 26 and 12.5 fs reveal significant changes of contrast, envelope
      function, and spatial frequency spectrum in comparison with continuous wave data.
      Evidence is presented that strong space-time coupling results in a time-dependent
      interference zone.

PMID- 18064248
TI  - Spectral phase correlation of coded femtosecond pulses by second-harmonic
      generation in thick nonlinear crystals.
AB  - We demonstrate a novel all-optical scheme for measuring the correlation of
      spectrally phase-coded ultrashort optical waveforms that uses second-harmonic
      generation (SHG) in long, periodically poled lithium niobate crystals. The SHG
      yield can be controlled over a range of ~30 dB, depending on the correlation of
      the applied phase codes. Such a spectral phase correlator has applications for
      ultrashort-pulse optical code-division multiple-access networking and could serve
      as a nonlinear optical but classical analog for certain schemes for coherent
      quantum control of multiphoton processes.

PMID- 18064249
TI  - Electrostrictive response in single-mode ring-index profile fibers: errata.

PMID- 18064250
TI  - Crucial effects of coupling coefficients on quasi-phase-matched harmonic
      generation in an optical superlattice: errata.

PMID- 18064251
TI  - Rigorous solution for transient propagation of electromagnetic waves through a
      medium: causality plus diffraction in time.
AB  - A rigorous solution for transient propagation of electromagnetic waves through a
      medium has been found. Because of this rigorousness, the solution exhibits
      apparent consistency with Einsteinian causality. Thus, it is confirmed that
      faster-than-light or superluminal propagation of electromagnetic waves is not
      possible. Evanescent transmission gives rise to diffraction in time, which is the
      actual reason for deformation of group propagation.

PMID- 18064252
TI  - Reflection from surfaces with a thin overlayer.
AB  - An approach to treating experimental reflectometry and ellipsometry data for bulk
      samples covered by an overlayer is suggested. This approach can be used for
      measurement of optical constants of solids, characterization of overlayers, and
      probing the abruptness of the spatial distribution of a bulk dielectric function.
      Numerical simulation shows that in the soft-x-ray and extreme-UV ranges the
      method can be applied for overlayers up to 3-8 nm thick.

PMID- 18064253
TI  - Wide angularly isotropic photonic bandgaps obtained from two-dimensional photonic
      crystals with Archimedean-like tilings.
AB  - We present a theoretical study of new two-dimensional photonic crystals based on
      Archimedean-like tilings. Three structures are considered: a square lattice with
      a 4-atom unit cell and triangular lattices with 7- and 13-atom unit cells. A 12
      fold local rotational symmetry is obtained for the triangular lattices and is
      approached for the square lattice. Wide photonic bandgaps can then be achieved,
      with very weak bandwidth dependence (~1%) on the wave-propagation direction. The
      complete bandgap frequency is shown to depend on the atomic bond length and not
      on the crystal period. This new class of periodic photonic crystals is a simple
      and attractive alternative to photonic quasi crystals.

PMID- 18064254
TI  - Electromagnetic optimization of multilevel diffractive elements by use of the
      wavelet transform.
AB  - We present an optimization algorithm for the design of multilevel diffractive
      optical elements in the electromagnetic domain. The method uses the wavelet
      transform to parameterize the diffractive optical elements according to a set of
      coefficients that corresponds to a multiresolution basis. Both local and global
      optimizations can be performed within a single algorithm. A design example
      consisting of the optimization of a two-dimensional millimeter-wave diffractive
      lens over a 10% bandwidth is presented.

PMID- 18064255
TI  - Simultaneous temperature and bend sensing with long-period fiber gratings.
AB  - Long-period gratings (LPG's) written in commercially available boron-codoped
      fibers operating at wavelengths of <1.1mum are shown to exhibit high temperature
      and bending sensitivities. Each resonant attenuation band of such LPG's was
      observed to split in two when the LPG's were bent. The split attenuation bands'
      separation increased significantly with increasing bend curvature, and the
      central wavelengths of the split bands provided a measure of temperature. We
      exploit this effect to allow for simultaneous measurement of temperature and
      bending in smart-structure applications. The demonstrated novel sensor system is
      simple and low cost.

PMID- 18064256
TI  - Dispersion-managed soliton propagation in short-period dispersion maps.
AB  - We show through detailed numerical simulations that stable dispersion-managed
      solitons exist in short-period dispersion maps characterized by a dispersion
      management period that is less than the amplifier spacing. These pulses show
      regular dynamics within the amplifier span and have greater energy enhancement
      than the conventional dispersion-managed soliton. We also show that greater
      interaction is obtained in this regime as a result of this increased enhancement.

PMID- 18064257
TI  - Two-pixel computer-generated hologram with a zero-twist nematic liquid-crystal
      spatial light modulator.
AB  - We present a method of producing a computer-generated hologram by use of a zero
      twist linear nematic liquid-crystal spatial light modulator. A 2x1 macro pixel
      method is used; one pixel represents the real data, and one, the imaginary. A
      method is shown that produces both positive and negative analog amplitude
      modulation.

PMID- 18064258
TI  - Efficient high-power diode-end-pumped TEM(00) Nd:YVO(4) laser with a planar
      cavity.
AB  - We demonstrate a compact and efficient diode-end-pumped TEM>(00) laser with
      output power of 30 W for 48 W of incident pump power by use of two coated Nd:YVO>
      (4) crystals to form a thermally stabilized flat-flat cavity. In Q -switched
      operation 25 W of average power at a pulse-repetition rate of 100 kHz and ~0.9-mJ
      pulse energy at a pulse-repetition rate of 10 kHz were produced.

PMID- 18064259
TI  - Frequency stabilization of a monolithic Nd:YAG ring laser by controlling the
      power of the laser-diode pump source.
AB  - The frequency of a 700-mW monolithic nonplanar Nd:YAG ring laser (NPRO) depends,
      with a large coupling coefficient (megahertz per milliwatt), on the power of its
      laser-diode pump source. Using this effect, we demonstrate frequency
      stabilization of a NPRO to a frequency reference by feeding back to the current
      of its pump diodes. We achieved an error-point frequency noise smaller than 1mHz/
      radicalHz and, simultaneously, a reduction of the power noise of the NPRO by 10
      dB without an additional power-stabilization feedback system.

PMID- 18064260
TI  - Demonstration of a 10-muJ tabletop laser at 52.9 nm in neonlike chlorine.
AB  - We report the demonstration of laser amplification at 52.9 nm in Ne-like Cl with
      a compact capillary discharge. Laser output pulses with energies of as much as 10
      muJ have been obtained. The beam divergence was approximately 4 mrad. This new
      23.4-eV tabletop laser is of particular interest for applications that require
      high peak fluxes of photons with energy slightly below the He photoionization
      threshold.

PMID- 18064261
TI  - Optimization of semiconductor quantum devices by evolutionary search.
AB  - A novel simulation strategy is proposed for searching for semiconductor quantum
      devices that are optimized with respect to required performances. Based on
      evolutionary programming, a technique that implements the paradigm of genetic
      algorithms in more-complex data structures than strings of bits, the proposed
      algorithm is able to deal with quantum devices with preset nontrivial constraints
      (e.g., transition energies, geometric requirements). Therefore our approach
      allows for automatic design, thus avoiding costly by-hand optimizations. We
      demonstrate the advantages of the proposed algorithm through a relevant and
      nontrivial application, the optimization of a second-harmonic-generation device
      working in resonance conditions.

PMID- 18064262
TI  - Simultaneous process of embossing and poling at elevated temperatures: a simple
      technique for nonlinear grating formation in polymer films.
AB  - A simple technique for fabrication of nonlinear gratings in polymer films, based
      on simultaneous embossing and poling, is proposed and demonstrated. A master
      grating consisting of a metal electrode with a dielectric die was fabricated and
      used for repeated embossing of the grating structures into nonlinear optical
      polymers at elevated temperatures. At the same time, we applied high voltage to
      the polymer films to induce second-order nonlinearity. The grating profile and
      the nonlinearity were estimated, as well as the mass productivity of nonlinear
      gratings.

PMID- 18064263
TI  - Double phase conjugation with orthogonally polarized beams in a BaTiO(3) crystal.
AB  - We have demonstrated experimentally the simultaneous self-conjugation of
      extraordinarily and ordinarily polarized light waves (lambda=514 nm), with the
      polarization state preserved, in a Ce:BaTiO(3) crystal. Conjugate o waves
      originate from coupling between o and e waves by means of a circular
      photogalvanic effect. The conjugator also takes advantage of the Ce:BaTiO(3)
      crystal, for which it is easy to generate an extraordinary conjugate beam by
      photorefractive backscattering. This beam of light is necessary for double phase
      conjugation.

PMID- 18064264
TI  - Second-order optical nonlinearity of 10-mum-thick periodically poled LiNbO(3)
      films.
AB  - We report on the fabrication and chic((2)) measurements of thin ~10-mum -thick
      films of periodically poled LiNbO(3), obtained by crystal ion slicing. The d(33)
      optical coefficient in the films is probed by sum-frequency generation with a
      short-pulse laser source at 1550 nm and compared with that of the bulk.
      Efficient, room-temperature TM(omega, m = 0)-to-TM(omega +omega, m = 0) mode
      conversion is obtained in the films. These measurements show that domain
      periodicity is preserved during ion implantation and that the thin films have
      bulklike nonlinearity and material dispersion.

PMID- 18064265
TI  - Self-guiding light in layered nonlinear media.
AB  - We study the propagation of intense optical beams in layered Kerr media. With
      appropriate shapes, beams with a power close to the self-focusing threshold are
      shown to propagate over long distances as quasi-stationary waveguides in cubic
      media supporting a periodic nonlinear refractive index.

PMID- 18064266
TI  - Sensitive H(2) detection by use of thermal-lens Raman spectroscopy without a
      tunable laser.
AB  - A new nonlinear Raman spectroscopy technique for trace-gas detection was proposed
      and demonstrated. The technique involved the use of a thermal-lens detection
      scheme to monitor thermal emission from the stimulated Raman process. We termed
      this technique thermal-lens Raman spectroscopy, and it was combined with a novel
      scheme involving a nonlinear Raman spectroscopy without a tunable laser. This
      technique was applied to detecting trace hydrogen molecules in the atmosphere by
      use of a pulsed Nd:YAG laser and a continuous-wave He-Ne probe laser. A detection
      limit of 9 parts in 10(6) was attained.

PMID- 18064267
TI  - Self-induced parametric amplification of high-order harmonics.
AB  - A theoretical analysis of self-induced parametric amplification of high-order
      harmonics is given. This mechanism permits the elimination of limitations on the
      harmonic-generation efficiency that are imposed by absorption.

PMID- 18064268
TI  - Design of cascaded diffractive phase elements for three-dimensional
      multiwavelength optical interconnects.
AB  - We propose a novel design method that incorporates multiple-layer relief profiles
      of diffractive phase elements to implement integrated operations on the incident
      beams according to their wavelengths. We demonstrate simultaneous wavelength
      division demultiplexing, arbitrary (even random) wavelength shuffling or routing,
      spatial focusing, and other manipulations of multiwavelength beams, such as
      irradiance profile shaping, with design examples for applications in three
      dimensional optical interconnects.

PMID- 18064269
TI  - Phase-locked white-light continuum pulses: toward a universal optical frequency
      comb synthesizer.
AB  - We demonstrate that two white-light continuum pulses that are independently
      generated by phase-locked ultrashort laser pulses are locked in phase and show
      surprisingly clear and stable Young interference fringes. The experiment shows
      that the two generated continua emit essentially in phase and that random phase
      jitter can remain negligible. This result is not only of interest for studies of
      nonlinear field-matter interactions but also suggests that such white-light
      continuum pulses can be used to realize a broad frequency comb for absolute
      frequency measurements from the IR to the UV.

PMID- 18064270
TI  - Five-optical-cycle pulse generation in the mid infrared from an optical
      parametric oscillator based on aperiodically poled lithium niobate.
AB  - We describe an optical parametric oscillator based on aperiodically poled lithium
      niobate that generates nearly transform-limited 53-fs duration pulses at a center
      wavelength of 3mum, corresponding to only 5 optical cycles. Results are presented
      illustrating the effect of pump- and grating-period chirp on the idler pulses,
      and a configuration capable of producing idler bandwidths in excess of 700 nm is
      discussed.

PMID- 18064271
TI  - Pulse characteristics of an optical parametric oscillator pumped by sub-30-fs
      light pulses.
AB  - We obtained nearly transform-limited light pulses of 34 fs near 1.2 microm by
      pumping an optical parametric oscillator with a 2-mm-long KTP crystal by 26-fs
      pulses from a Ti:sapphire laser. The average power of the pulses that were
      obtained was greater than 50 mW, at an 80-MHz repetition rate. Attempts to
      downscale the pulse duration by decreasing the pump-pulse duration revealed
      remarkable limitations of the attainable pulse length for sub-30-fs pump pulses,
      in accordance with a recent theoretical study [J. Opt. Soc. Am. B 17, 741
      (2000)].

PMID- 18064272
TI  - Time-averaged total force on a dipolar sphere in an electromagnetic field.
AB  - We establish the time-averaged total force on a subwavelength-sized particle in a
      time-harmonic-varying field. Our analysis is not restricted to the spatial
      dependence of the incident field. We discuss the addition of the radiative
      reaction term to the polarizability to deal correctly with the scattering force.
      As an illustration, we assess the degree of accuracy of several previously
      established polarizability models.

PMID- 18064273
TI  - Measurement of complex surface deformation by high-speed dynamic phase-stepped
      digital speckle pattern interferometry.
AB  - We describe a high-speed digital speckle pattern interferometer incorporating a
      line-scan camera and a waveguide phase modulator for the measurement of complex
      deformation (vibration phase and amplitude) at audio acoustic frequencies.
      Experimental data show continuous phase-stepped recovery of out-of-plane surface
      deformation in one dimension, obtained at 100 kHz with 2pi/20-rad (0.02-mum)
      displacement resolution, for surface velocities of 3.2 mm s>(-1) .

PMID- 18064274
TI  - Direct observation of a propagating, planar-waveguide surface mode in a
      discontinuous film of metal nanoparticles.
AB  - We report the observation of p-polarized guided waves that propagate confined to
      the surface of a two-dimensional array of silver (Ag) nanoparticles of average
      particle diameter and film thickness of approximately 400 and 154 nm,
      respectively, and comparable interparticle spacing. We interpret resonant
      features in the attenuated total reflection angular spectrum as arising from the
      excitation of guided waves in our discontinuous samples. The excitation of these
      waves is a direct consequence of the interaction of the light field with the
      localized resonance of the conduction electrons in the individual metal
      nanoparticles.

PMID- 18064275
TI  - Quasi-distributed strain sensing with white-light interferometry: a novel
      approach.
AB  - An optical fiber ring is used to generate multiple reference waves in a
      multiplexed fiber-optic Michelson-type sensor array. The array consists of N
      sensing segments connected in series along a single optical fiber path and is
      interrogated with a white-light interferometric technique. Experimental results
      with a two-sensor array are presented.

PMID- 18064276
TI  - Optical computing by a vector holographic memory system.
AB  - We propose what is to our knowledge a novel holographic memory system that is
      simultaneously applicable to data storage and optical computing. We introduce a
      polarization-modulated reference beam into holographic recording. A desired
      spatial-frequency component of an object beam is recorded as a polarization
      modulated grating, and the other component is recorded as an intensity-modulated
      grating. Since the polarization-modulated grating rotates the polarization axis
      of the incident light by 90 degrees , it is possible to distinguish the desired
      spatial-frequency component of the retrieved image. Utilizing this property, we
      have successfully performed spatial-frequency filtering and frequency-selective
      matched filtering. The system is capable of a variety of optical computations,
      depending on the design of the polarization modulation.

PMID- 18064277
TI  - Dynamic properties of bacteriorhodopsin exposed to ultrashort light pulses.
AB  - Bacteriorhodopsin (BR) in its metastable form was used for pulsed holographic
      recording at lambda~400nm . It is shown that the properties of BR are insensitive
      to changes in the writing light's pulse width. When holograms are recorded in the
      BR stable form (lambda~600 nm) , the sensitivity of the medium and the
      diffraction efficiency of those holograms are reduced proportionally to the
      decrease in the light's pulse width.

PMID- 18064278
TI  - Closed-loop aberration correction by use of a modal Zernike wave-front sensor.
AB  - We describe the practical implementation of a closed-loop adaptive-optics system
      incorporating a novel modal wave-front sensor. The sensor consists of a static
      binary-phase computer-generated holographic element, which generates a pattern of
      spots in a detector plane. Intensity differences between symmetric pairs of these
      spots give a direct measure of the Zernike mode amplitudes that are present in
      the input wave front. We use a ferroelectric liquid-crystal spatial light
      modulator in conjunction with a 4-f system and a spatial filter as a wave-front
      correction element. We present results showing a rapid increase in Strehl ratio
      and focal spot quality as the system corrects for deliberately introduced
      aberrations.

PMID- 18064279
TI  - Four-wave mixing and edge-enhanced optical correlation in a Ce:KNSBN crystal.
AB  - In the case of degenerate four-wave mixing in a cerium-doped potassium sodium
      strontium barium niobate (Ce:KNSBN) crystal, it is found that the transmission
      grating is dominant when the incident beams are extraordinarily polarized, the
      crystal response is more rapid, and the conjugate beam is more intense.
      Furthermore, the variation of the conjugate beam intensity forms a loop as the
      fringe modulation of the transmission grating varies. Based on this observation,
      we have implemented edge enhancement of an image and edge-enhanced optical
      correlation via four-wave mixing in a Ce:KNSBN crystal without the requirement of
      reversal of the signal-pump-beam intensity ratio.

PMID- 18064280
TI  - Robust wave-front estimation from multiple directional derivatives.
AB  - A quadratic cost functional for computing an estimate of a wave front from
      multiple directional derivatives is presented. This functional is robust to noise
      and is specially suited for moire deflectometry, Ronchi testing, and lateral
      shearing interferometry.

PMID- 18064281
TI  - Fourier-modal methods applied to waveguide computational problems.
AB  - Rigorous coupled-wave analysis (also called the Fourier-modal method) is an
      efficient tool for the numerical analysis of grating diffraction problems. We
      show that, with only a few modifications, this method can be used efficiently for
      the numerical analysis of aperiodic diffraction problems, including photonic
      crystal waveguides, Bragg mirrors, and grating couplers. We thus extend the
      domain of applications of grating theories.

PMID- 18064282
TI  - Noise-assisted binary information transmission in vertical cavity surface
      emitting lasers.
AB  - The response of a polarization-bistable vertical cavity surface emitting laser to
      a small amplitude, pseudorandom binary signal is experimentally studied. A high
      contrast output is obtained when the optimum amount of noise is added to the
      system. The quality of the transmission, measured by the bit-error rate, exhibits
      a resonantlike behavior as a function of the input noise. We analyze possible
      applications of this transmission scheme to optical communications and compare it
      with those used in a standard amplitude modulation scheme.

PMID- 18064283
TI  - Diode laser frequency-noise suppression by >50dB by use of electro-optic
      parametric master oscillators.
AB  - We demonstrate a novel frequency-stabilization scheme for laser diodes that is
      capable of linewidth reduction by more than 5 orders of magnitude. In this master
      slave scheme the diode laser emission is frequency-offset phase locked to the
      emission of an electro-optic parametric oscillator (EOPO), and the laser diode is
      simultaneously used as the EOPO pump source. As a result the initial frequency
      fluctuations of the pump are reduced to the intrinsic noise level of the EOPO,
      which can be extremely small. We demonstrate that subhertz linewidths of the beat
      notes of the signals of two of these systems can be readily achieved if acoustic
      perturbations are suppressed.

PMID- 18064284
TI  - Laser-diode-pumped Cr(4)+, Nd(3)+:YAG with self-Q-switched laser output of 1.4 W.
AB  - By use of a laser diode as a pump source, a self-Q-switched laser from a Cr,
      Nd:YAG crystal is demonstrated. The output Q-switched traces are very stable, the
      threshold pump power is 3.5 W, the pulse duration is 50 ns, and the slope
      efficiency is as high as 20%. In addition, the pulse width remains constant while
      the pulse repetition rate varies with pump power.

PMID- 18064285
TI  - Selective delivery of laser energy to biological tissue based on refractive-index
      differences.
AB  - We report a novel method for selective laser energy delivery into biological
      tissues based on refractive-index differences. As a specific example, Ho:YAG
      laser energy is delivered into fat preferentially over other soft tissue, despite
      the fact that water has a higher absorption coefficient at this wavelength than
      fat.

PMID- 18064286
TI  - Atomic-force microscope observation and molecular-scale flattening of the single
      crystal surface of 4-dimethylamino-N-methyl-4-stilbazolium tosylate (DAST).
AB  - The surface of an organic electro-optic crystal tends to be covered with a
      degenerate rough layer, which may cause light scattering or unfavorable
      transmission of light. We demonstrate a novel method of removing this layer and
      flattening the (001) surface of a 4-dimethylamino- N -methyl-4-stilbazolium
      tosylate (DAST) crystal on a molecular scale by applying suitable force on the
      tip of an atomic-force microscope (AFM). When the loading force on the AFM tip is
      kept near 10 nN, the DAST molecules can be removed layer by layer. This method
      produced a large, flat terrace of 250,000 nm(2) , and the molecular-scale
      flatness of this area was confirmed by AFM observation.

PMID- 18064287
TI  - Real three-dimensional microstructures fabricated by photopolymerization of
      resins through two-photon absorption.
AB  - Effective energy windows for two-photon absorption (TPA) photopolymerization of
      resins were investigated and, with a properly selected laser pulse energy,
      exquisite three-dimensional (3D) microstructures with submicrometer spatial
      resolution were achieved. The results show the inherent utility of TPA in the
      fabrication of real 3D patterns. In particular, we propose and utilize a resin
      pre-exposure technique by which freely movable components affixed to an axle are
      built, demonstrating a new application of TPA in laser microfabrication.

PMID- 18064288
TI  - Observation of two-dimensional multimode solitons.
AB  - We present the first experimental observation of (2+1) -dimensional multimode
      (composite) solitons. A single-hump component and a double-hump (dipole-type)
      component are jointly self-trapped as a composite soliton in a biased
      photorefractive crystal.

PMID- 18064289
TI  - Generation of femtosecond radiation at 211 nm by femtosecond pulse upconversion
      in the field of a picosecond pulse.
AB  - We show that, in the case of sum-frequency mixing, one can alleviate group
      velocity mismatch between IR and UV pulses by choosing different pulse widths,
      thus extending the interaction length of ultrashort pulses within nonlinear
      crystals. By fifth-harmonic generation with a Nd:glass laser, we demonstrate
      efficient frequency upconversion of 195-fs 264-nm pulses under the envelope of
      0.9-ps 1055-nm pulses in beta-barium borate crystal, yielding <270-fs pulses with
      energy of up to 110muJ at 211 nm.

PMID- 18064290
TI  - Diode-pumped femtosecond Yb:KGd(WO(4))(2) laser with 1.1-W average power.
AB  - We demonstrate what is to our knowledge the first mode-locked Yb:KGd(WO(4))(2)
      laser. Using a semiconductor saturable-absorber mirror for passive mode locking,
      we obtain pulses of 176-fs duration with an average power of 1.1 W and a peak
      power of 64 kW at a center wavelength of 1037 nm. We achieve pulses as short as
      112 fs at a lower output power. The laser is based on a standard delta cavity and
      pumped by two high-brightness laser diodes, making the whole system very simple
      and compact. Tuning the laser by means of a knife-edge results in mode-locked
      pulses within a wavelength range from 1032 to 1054 nm. In cw operation, we
      achieve output powers as high as 1.3 W.

PMID- 18064291
TI  - Near-field terahertz imaging with a dynamic aperture.
AB  - By introduction of an optical gating beam on a semiconductor wafer, near-field
      terahertz (THz) imaging with a dynamic aperture has been realized. The spatial
      resolution is determined by the focus size of the optical gating bean and the
      near-field diffraction effect. THz imaging with subwavelength spatial resolution
      (better than 50mum) is demonstrated.

PMID- 18064292
TI  - Generation of relativistic intensity pulses at a kilohertz repetition rate.
AB  - By using adaptive optics to correct the wave-front distortion of a 21-fs, 0.7-mJ,
      1-kHz laser, we are able to focus the pulses to a 1-mum spot with an f/1 off-axis
      parabolic mirror. The peak intensity at the focal position is 1.5x10(18) W/cm(2)
      , which is to the authors' knowledge the first demonstration of generating
      relativistic intensity at a kilohertz repetition rate.

PMID- 18064293
TI  - Fluorous 2,4-Dichloro-1,3,5-triazine (F-DCT) as Amide Coupling Agent.

PMID- 18064294
TI  - Fluorous 2,4-Dichloro-1,3,5-triazines (F-DCTs) as Nucleophile Scavengers.

PMID- 18064295
TI  - SMOKE 'EM IF YOU GOT 'EM: CIGARETTE BLACK MARKETS IN U.S. PRISONS AND JAILS.
AB  - Since the mid-1980s, cigarette-smoking policies have become increasingly
      restrictive in jails and prisons across the United States. Cigarette black
      markets of various form and scale often emerge in jails and prisons where tobacco
      is prohibited or banned. Case studies of 16 jails and prisons were undertaken to
      understand the effects of cigarette bans versus restrictions on inmate culture
      and prison economies. This study describes how bans can transform largely benign
      cigarette "gray markets," where cigarettes are used as a currency, into more
      problematic black markets, where cigarettes are a highly priced commodity.
      Analysis points to several structural factors that affected the development of
      cigarette black markets in the visited facilities: the architectural design,
      inmate movement inside and outside, officer involvement in smuggling cigarettes
      to inmates, and officer vigilance in enforcing the smoking policy. Although these
      factors affect the influx of other types of contraband into correctional
      facilities, such as illegal drugs, this study argues that the demand and
      availability of cigarettes creates a unique kind of black market.

PMID- 18064297
TI  - A Phantom Study of Magnetoacoustic Tomography with Magnetic Induction (MAT-MI)
      for Imaging Electrical Impedance of Biological Tissue.
AB  - An experimental feasibility study was conducted on Magnetoacoustic-Tomography
      with Magnetic Induction (MAT-MI). It is demonstrated that the 2-dimensional (2D)
      MAT-MI system can detect and image the boundaries between regions of different
      electrical conductivity with high spatial resolution. Utilizing a magnetic
      stimulation coil, MAT-MI evokes magnetically induced eddy current in an object
      which is placed in a static magnetic field. Because of the existence of Lorenz
      forces, the eddy current in turn causes acoustic vibrations, which are measured
      around the object in order to reconstruct the electrical impedance distribution
      of the object. The present experimental results from the saline and gel phantoms
      are promising and suggest the merits of MAT-MI in imaging electrical impedance of
      biological tissue with high spatial resolution.

PMID- 18064298
TI  - Immunoglobulin diversity gene usage predicts unfavorable outcome in a subset of
      chronic lymphocytic leukemia patients.
AB  - Survival of patients with B cell chronic lymphocytic leukemia (B-CLL) can be
      predicted by analysis of mutations in the immunoglobulin heavy chain variable
      gene (IGHV). Patients without mutations (unmutated [UM]) are at greater risk for
      disease progression and death than patients with mutations (M). Despite this
      broad prognostic difference, there remains wide intragroup variation in the
      clinical outcome of UM patients, especially those with low/intermediate Rai risk
      disease. We evaluated UM B-CLL patients with low/intermediate Rai risk to
      determine the relationship between IGHV, IGH diversity (IGHD), and IGH joining
      (IGHJ) gene usage and time to treatment (TTT). Irrespective of IGHV usage, UM
      patients whose B-CLL cells expressed the IGHD3-3 gene had a significantly shorter
      TTT than other UM B-CLL patients, and specifically, use of the IGHD3-3 gene in
      reading frame 2 (RF2) predicted shorter TTT. As expected, Rai risk was the best
      single prognostic factor for TTT; however, IGHD usage was also a significant
      variable for TTT. Therefore, both IGHD gene and IGHD RF usage have prognostic
      relevance in UM B-CLL patients with low/intermediate Rai risk disease. In
      addition, these data support the concept that antigen-driven selection of
      specific Ig receptors plays a role in the clinical course of B-CLL.

PMID- 18064299
TI  - Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin
      production in human CD34+ cells.
AB  - Sickle-cell disease (SCD) and beta thalassemia constitute worldwide public health
      problems. New therapies, including hydroxyurea, have attempted to augment the
      synthesis of fetal hemoglobin (HbF) and improve current treatment. Lenalidomide
      and pomalidomide are members of a class of immunomodulators used as anticancer
      agents. Because clinical trials have demonstrated that lenalidomide reduces or
      eliminates the need for transfusions in some patients with disrupted blood cell
      production, we investigated the effects of lenalidomide and pomalidomide on
      erythropoiesis and hemoglobin synthesis. We used an in vitro erythropoiesis model
      derived from human CD34+ progenitor cells from normal and SCD donors. We found
      that both compounds slowed erythroid maturation, increased proliferation of
      immature erythroid cells, and regulated hemoglobin transcription, resulting in
      potent induction of HbF without the cytotoxicity associated with other HbF
      inducers. When combined with hydroxyurea, pomalidomide and, to a lesser extent,
      lenalidomide were found to have synergistic effects on HbF upregulation. Our
      results elucidate what we believe to be a new mechanism of action of pomalidomide
      and lenalidomide and support the hypothesis that pomalidomide, used alone or in
      combination with hydroxyurea, may improve erythropoiesis and increase the ratio
      of fetal to adult hemoglobin. These findings support the evaluation of
      pomalidomide as an innovative new therapy for beta-hemoglobinopathies.

PMID- 18064300
TI  - SR-BI protects against endotoxemia in mice through its roles in glucocorticoid
      production and hepatic clearance.
AB  - Septic shock results from an uncontrolled inflammatory response, mediated
      primarily by LPS. Cholesterol transport plays an important role in the host
      response to LPS, as LPS is neutralized by lipoproteins and adrenal cholesterol
      uptake is required for antiinflammatory glucocorticoid synthesis. In this study,
      we show that scavenger receptor B-I (SR-BI), an HDL receptor that mediates HDL
      cholesterol ester uptake into cells, is required for the normal antiinflammatory
      response to LPS-induced endotoxic shock. Despite elevated plasma HDL levels, SR
      BI-null mice displayed an uncontrollable inflammatory cytokine response and a
      markedly higher lethality rate than control mice in response to LPS. In addition,
      SR-BI-null mice showed a lack of inducible glucocorticoid synthesis in response
      to LPS, bacterial infection, stress, or ACTH. Glucocorticoid insufficiency in SR
      BI-null mice was due to primary adrenal malfunction resulting from deficient
      cholesterol delivery from HDL. Furthermore, corticosterone supplementation
      decreased the sensitivity of SR-BI-null mice to LPS. Plasma from control and SR
      BI-null mice exhibited a similar ability to neutralize LPS, whereas SR-BI-null
      mice showed decreased plasma clearance of LPS into the liver and hepatocytes
      compared with normal mice. We conclude that SR-BI in mice is required for the
      antiinflammatory response to LPS-induced endotoxic shock, likely through its
      essential role in facilitating glucocorticoid production and LPS hepatic
      clearance.

PMID- 18064301
TI  - Small intestinal CD8+TCRgammadelta+NKG2A+ intraepithelial lymphocytes have
      attributes of regulatory cells in patients with celiac disease.
AB  - Intraepithelial lymphocytes (IELs) bearing the gammadelta TCR are more abundant
      in the small intestinal mucosa of patients with celiac disease (CD) compared with
      healthy individuals. However, their role in disease pathogenesis is not well
      understood. Here, we investigated the functional attributes of TCRgammadelta+
      IELs isolated from intestinal biopsies of patients with either active celiac
      disease (ACD) or those on a gluten-free diet (GFD). We found that compared with
      individuals with ACD, individuals on GFD have a higher frequency of
      CD8+TCRgammadelta+ IELs that express the inhibitory NK receptor NKG2A and
      intracellular TGF-beta1. TCR triggering as well as cross-linking of NKG2A
      increased both TGF-beta1 intracellular expression and secretion in vitro.
      Coculture of sorted TCRgammadelta+NKG2A+ IELs, IL-15-stimulated TCRalphabeta+
      IELs, and HLA-E+ enterocytes resulted in a decreased percentage of cytotoxic
      CD8+TCRalphabeta+ IELs expressing intracellular IFN-gamma and granzyme-B and
      surface NKG2D. This inhibition was partially abrogated by blocking either TGF
      beta alone or both NKG2A and HLA-E. Thus, our data indicate that suppression was
      at least partially mediated by TGF-beta secretion as a result of engagement of
      NKG2A with its ligand, HLA-E, on enterocytes and/or TCRalphabeta+ IELs. These
      findings demonstrate that human small intestinal CD8+TCRgammadelta+ IELs may have
      regulatory potential in celiac disease.

PMID- 18064302
TI  - Selective inhibition of proprotein convertases represses the metastatic potential
      of human colorectal tumor cells.
AB  - The proprotein convertases (PCs) are implicated in the activation of various
      precursor proteins that play an important role in tumor cell metastasis. Here, we
      report their involvement in the regulation of the metastatic potential of
      colorectal tumor cells. PC function in the human and murine colon carcinoma cell
      lines HT-29 and CT-26, respectively, was inhibited using siRNA targeting the PCs
      furin, PACE4, PC5, and PC7 or by overexpression of the general PC inhibitor
      alpha1-antitrypsin Portland (alpha1-PDX). We found that overexpression of alpha1
      PDX and knockdown of furin expression inhibited processing of IGF-1 receptor and
      its subsequent activation by IGF-1 to induce IRS-1 and Akt phosphorylation, all
      important in colon carcinoma metastasis. These data suggest that the PC furin is
      a major IGF-1 receptor convertase. Expression of alpha1-PDX reduced the
      production of TNF-alpha and IL-1alpha by human colon carcinoma cells, and
      incubation of murine liver endothelial cells with conditioned media derived from
      these cells failed to induce tumor cell adhesion to activated murine endothelial
      cells, a critical step in metastatic invasion. Furthermore, colon carcinoma cells
      in which PC activity was inhibited by overexpression of alpha1-PDX when injected
      into the portal vein of mice showed a significantly reduced ability to form liver
      metastases. This suggests that inhibition of PCs is a potentially promising
      strategy for the prevention of colorectal liver metastasis.

PMID- 18064303
TI  - Variation in use of erythrocyte invasion pathways by Plasmodium falciparum
      mediates evasion of human inhibitory antibodies.
AB  - Antibodies that inhibit Plasmodium falciparum invasion of erythrocytes are
      believed to be an important component of immunity against malaria. During blood
      stage infection, P. falciparum can use different pathways for erythrocyte
      invasion by varying the expression and/or utilization of members of 2 invasion
      ligand families: the erythrocyte-binding antigens (EBAs) and reticulocyte-binding
      homologs (PfRhs). Invasion pathways can be broadly classified into 2 groups based
      on the use of sialic acid (SA) on the erythrocyte surface by parasite ligands. We
      found that inhibitory antibodies are acquired by malaria-exposed Kenyan children
      and adults against ligands of SA-dependent and SA-independent invasion pathways,
      and the ability of antibodies to inhibit erythrocyte invasion depended on the
      pathway used by P. falciparum isolates. Differential inhibition of P. falciparum
      lines that varied in their use of specific EBA and PfRh proteins pointed to these
      ligand families as major targets of inhibitory antibodies. Antibodies against
      recombinant EBA and PfRh proteins were acquired in an age-associated manner, and
      inhibitory antibodies against EBA175 appeared prominent among some individuals.
      These findings suggest that variation in invasion phenotype might have evolved as
      a mechanism that facilitates immune evasion by P. falciparum and that a broad
      inhibitory response against multiple ligands may be required for effective
      immunity.

PMID- 18064304
TI  - Glypican-1 modulates the angiogenic and metastatic potential of human and mouse
      cancer cells.
AB  - Cells isolated from many types of human cancers express heparin-binding growth
      factors (HBGFs) that drive tumor growth, metastasis, and angiogenesis. The
      heparan sulfate proteoglycan glypican-1 (GPC1) is a coreceptor for HBGFs. Here we
      show that both cancer cell-derived and host-derived GPC1 are crucial for
      efficient growth, metastasis, and angiogenesis of human and mouse cancer cells.
      Thus downregulation of GPC1 in the human pancreatic cancer cell line PANC-1,
      using antisense approaches, resulted in prolonged doubling times and decreased
      anchorage-independent growth in vitro as well as attenuated tumor growth,
      angiogenesis, and metastasis when these cells were transplanted into athymic
      mice. Moreover, athymic mice that lacked GPC1 exhibited decreased tumor
      angiogenesis and metastasis following intrapancreatic implantation with either
      PANC-1 or T3M4 human pancreatic cancer cells and fewer pulmonary metastases
      following intravenous injection of murine B16-F10 melanoma cells. In addition,
      hepatic endothelial cells isolated from these mice exhibited an attenuated
      mitogenic response to VEGF-A. These data indicate that cancer cell- and host
      derived GPC1 are crucial for full mitogenic, angiogenic, and metastatic potential
      of cancer cells. Thus targeting GPC1 might provide new avenues for cancer therapy
      and for the prevention of cancer metastasis.

PMID- 18064306
TI  - The problem of risk assessment and prophylaxis of venous thromboembolism in
      pregnancy.

PMID- 18064305
TI  - Heparan sulfate and syndecan-1 are essential in maintaining murine and human
      intestinal epithelial barrier function.
AB  - Patients with protein-losing enteropathy (PLE) fail to maintain intestinal
      epithelial barrier function and develop an excessive and potentially fatal efflux
      of plasma proteins. PLE occurs in ostensibly unrelated diseases, but emerging
      commonalities in clinical observations recently led us to identify key players in
      PLE pathogenesis. These include elevated IFN-gamma, TNF-alpha, venous
      hypertension, and the specific loss of heparan sulfate proteoglycans from the
      basolateral surface of intestinal epithelial cells during PLE episodes. Here we
      show that heparan sulfate and syndecan-1, the predominant intestinal epithelial
      heparan sulfate proteoglycan, are essential in maintaining intestinal epithelial
      barrier function. Heparan sulfate- or syndecan-1-deficient mice and mice with
      intestinal-specific loss of heparan sulfate had increased basal protein leakage
      and were far more susceptible to protein loss induced by combinations of IFN
      gamma, TNF-alpha, and increased venous pressure. Similarly, knockdown of syndecan
      1 in human epithelial cells resulted in increased basal and cytokine-induced
      protein leakage. Clinical application of heparin has been known to alleviate PLE
      in some patients but its unknown mechanism and severe side effects due to its
      anticoagulant activity limit its usefulness. We demonstrate here that non
      anticoagulant 2,3-de-O-sulfated heparin could prevent intestinal protein leakage
      in syndecan-deficient mice, suggesting that this may be a safe and effective
      therapy for PLE patients.

PMID- 18064307
TI  - The fine-tuning of anti-oxidized low-density lipoprotein antibodies in
      cardiovascular disease and thrombosis.
AB  - Anti-oxidised low-density lipoprotein (anti-oxLDL) antibodies are a heterogeneous
      group of autoantibodies including both pathogenic and protective subsets. Whereas
      in most studies the levels of anti-oxLDL antibodies were associated with enhanced
      atherosclerosis as evaluated by different methods, immunization with oxLDL leads
      to elevated levels of anti-oxLDL and protection against atherosclerosis. Anti
      oxLDL can also be used for immunomodulation of atherosclerosis (i.e. possible
      therapeutic use of intravenous immunoglobulin, oral tolerance). More specific
      autoantibodies out of total anti-oxLDL should be selected, for instance, anti
      oxLDL/beta-2-glycoprotein I complex, hence defining the fine-tuning of anti-oxLDL
      antibodies might detect which autoantibodies are pathogenic and which can be used
      therapeutically.

PMID- 18064308
TI  - Plasma cholesteryl ester transfer protein and blood coagulability.
AB  - Dyslipoproteinemia involving low levels of high density lipoprotein (HDL) is
      linked to venous thrombosis in young male adults and to recurrence of venous
      thrombosis in patients who have experienced a previous unprovoked venous
      thrombosis episode. Plasma cholesteryl ester transfer protein (CETP) modulates
      HDL metabolism and some lipoproteins can affect blood coagulation reactions with
      either procoagulant or anticoagulant effects. Hence, we evaluated relationships
      between the mass of CETP and blood coagulability in plasma samples from 39 normal
      healthy adults. For clotting initiated by dilute tissue factor or factor XIa,
      clotting times significantly correlated with CETP antigen levels. Thus,
      coagulation initiated by either the extrinsic or intrinsic coagulation pathway is
      positively correlated with CETP plasma levels. When added to plasma, a
      recombinant CETP preparation dose-dependently shortened factor Xa-1-stage
      clotting times, showing that it augmented procoagulant activity in plasma. In
      reaction mixtures containing purified factors Xa and Va and prothrombin, the
      recombinant CETP preparation dose-dependently increased prothrombin activation,
      suggesting it specifically enhances prothrombinase activity. Thus, our data
      highlight a previously unknown positive relationship between CETP plasma levels
      and blood coagulability that might relate to risks for thrombotic events.

PMID- 18064309
TI  - A nonstop mutation in the factor (F)X gene of a severely haemorrhagic patient
      with complete absence of coagulation FX.
AB  - We identified a previously unknown mutation by sequencing the factor (F)X gene in
      a severely haemorrhagic 14-year-old male African-American individual with
      undetectable plasma FX-activity and -antigen levels. This mutation, called F10
      Augusta, was homozygote and is a combination of an 8bp insertion in flanking 3'
      genomic-DNA and a 5bp terminal exon-8 deletion involving codons 437 and 438.
      Sequencing of RT-PCR and 3'-RACE products showed that the F10-Augusta transcript
      is normally processed but lacks an in-frame stop codon. An allele specific 3'
      RACE-based RFLP assay demonstrated that the steady-state concentration of the
      mutant transcript was markedly lower than that of the wild-type message in total
      RNA samples from the patient's unaffected heterozygous parents. The recently
      discovered nonstop decay mechanism, a component pathway of the mRNA surveillance
      system, is a possible explanation for the reduced concentration of the mutant FX
      transcript. This is the first report implying such a mechanism in the
      pathogenesis of inherited bleeding disorders.

PMID- 18064310
TI  - Localization of the low-density lipoprotein receptor-related protein regions
      involved in binding to the A2 domain of coagulation factor VIII.
AB  - Catabolism of coagulation factor VIII (FVIII) is mediated by low-density
      lipoprotein receptor-related protein (LRP). The ligand-binding sites of LRP are
      formed by complement-type repeats (CR), and CR clusters II and IV bind most of
      LRP ligands. FVIII contains two major LRP-binding sites located in the A2 and A3
      domains. This study was aimed to identify specific complement-type repeats of LRP
      involved in interaction with the A2 site and to probe their functional importance
      in A2 catabolism. We generated individual LRP clusters II, III and IV, along with
      nine overlapping CR triplets encompassing clusters II and IV in a baculovirus
      expression system and studied their interaction with isolated A2. In surface
      plasmon resonance (SPR) assay, A2 bound to clusters II and IV with KDs 22 and 39
      nM, respectively, and to the majority of CR triplets with affinities in the range
      of KDs 25-90 nM. Similar affinities were determined for A2 interaction with a
      panel of CR doublets overlapping cluster II (CR 3-4, 4-5, 5-6, 6-7 and 7-8).
      These LRP fragments inhibited the binding of 125I-A2 to LRP in solid-phase assay,
      LRP-mediated internalization of 125I-A2 in cell culture and 125I-A2 clearance
      from the mouse circulation. Point mutations of critical A2 residues of the
      LRPbinding site resulted in differential reduction or abolishment of its binding
      to LRP fragments. We conclude that A2 interacts with LRP via multiple binding
      sites spanning CR 3-8 in cluster II and CR 23-29 in cluster IV, and the minimal
      A2-binding unit of LRP is formed by two adjacent CR.

PMID- 18064311
TI  - A novel von Willebrand factor mutation (I1372S) associated with type 2B-like von
      Willebrand disease: an elusive phenotype and a difficult diagnosis.
AB  - Mutations in the A1 domain of von Willebrand factor (VWF) may be associated with
      gain of function in the VWF-platelet GPIb interaction and consumption of large
      VWF multimers, as seen in type 2B von Willebrand disease (VWD). We report a new
      VWF abnormality associated with greater VWF-GPIb interaction in the presence of
      all VWF multimers. The index case is a woman with a lifelong history of bleeding,
      found hyperresponsive to ristocetin with spontaneous platelet aggregation (SPA).
      She had normal factor VIII, VWF:Ag, VWF:RCo and VWF:CB levels, normal
      VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios, and a full panel of plasma and platelet
      VWF multimers. A missense mutation (4115T>G) was found in exon 28 of the VWF
      gene, which replaced a isoleucine with a serine at position 1372 of pre-pro-VWF
      (I1372S) at heterozygous level. Recombinant VWF carrying the I1372S mutation and
      showing a normal VWF multimer organisation was capable of inducing SPA on normal
      platelet-rich plasma (unlike wild-type VWF), as well as a hyper-response to
      ristocetin in the same platelets (0.6 mg/ml ristocetin vs. 1.2 of wild-type VWF).
      The new I1372S VWF mutation, characterized by SPA and hyper-responsiveness to
      ristocetin thus has some of the features of type 2B VWD, but not the lack of
      large VWF multimers, so we defined this variant as type 2B-like VWD. Why I1372S
      VWF is associated with bleeding symptoms, despite normal VWF levels and multimer
      organisation, remains to be seen.

PMID- 18064312
TI  - Low risk of inhibitor formation in haemophilia patients after a change in
      treatment from Chinese hamster ovary cell-produced to baby hamster kidney cell
      produced recombinant factor VIII.
AB  - This retrospective survey of haemophilia A patients from multiple treatment
      centres in Ireland assessed the development of inhibitors following a switch in
      the prescribed treatment from recombinant factor VIII (rFVIII) produced by
      Chinese hamster ovary (CHO) cells (rFVIII-CHO) to rFVIII produced by baby hamster
      kidney (BHK) cells (rFVIII-BHK). Ninety-four patients participated in the survey.
      Most patients (89.4%) had severe haemophilia. One of 77 (1.3%) patients with no
      inhibitor history developed an inhibitor. This was a patient with moderate
      haemophilia. A who developed a transient, low-titre (1 BU) de novo inhibitor
      following surgery. Recurrent inhibitors were detected in three of 17 patients
      with an inhibitor history during the 20-month post-switch study period. All
      patients continued on rFVIII-BHK therapy, and all tested negative for inhibitors
      at the time of their last inhibitor assay during the observation period. These
      results are consistent with the low levels of inhibitor formation demonstrated in
      phase III studies of previously treated patients receiving BHK-produced rFVIII
      and support the low risk of inhibitor formation following a change from rFVIII
      CHO to rFVIII-BHK.

PMID- 18064313
TI  - Heparanase modulates heparinoids anticoagulant activities via non-enzymatic
      mechanisms.
AB  - A key element for the physiological restriction of blood coagulation at the
      endothelial cell surface is its non-thrombogenic property, mainly attributed to
      cell surface heparan sulfate proteoglycans. Heparanase is an endo-beta-D
      glucuronidase with specific heparan sulfate degrading activity, which is produced
      and stored in platelets, and is released upon their activation. We examined the
      effects of heparanase pro-enzyme on coagulation functions, predominantly under
      physiological conditions. While heparanase pro-enzyme does not directly affect
      coagulation protein activities, it has profound effects on heparinoid-mediated
      regulation of coagulation responses, apparently via mechanisms that do not
      involve its enzymatic activity. Heparanase pro-enzyme reverses the anti-coagulant
      activity of unfractionated heparin on the coagulation pathway as well as on
      thrombin activity. In addition, heparanase pro-enzyme abrogated the factor X
      inhibitory activity of low-molecular-weight heparin (LMWH). The pro-coagulant
      effects of the non-active heparanase were also exerted by its major functional
      heparin-binding peptide. Finally, the effects of heparanase on the activity of
      factor VII activating protease that is auto-activated by heparinoids indicated a
      complete antagonistic action of heparanase in this system. Altogether, heparanase
      pro-coagulant activities that were also demonstrated in plasma samples from
      patients under LMWH treatment, point to a possible use of this molecule as
      antagonist for heparinoid treatment.

PMID- 18064314
TI  - Use of the pentasaccharide fondaparinux as an anticoagulant during haemodialysis.
AB  - No data about the use of the pentasaccharide fondaparinux, a highly selective
      indirect inhibitor of factor Xa, in patients treated with haemodialysis are
      available. Therefore, we investigated the pharmacokinetics and -dynamics of
      fondaparinux in 12 patients during haemodialysis. The anti-Xa activity (expressed
      as fondaparinux equivalent) was monitored, a semiquantitative clotting scale
      (SQCS) ranging from 0 (no visible traces of coagula) to 3 (complete clotting of
      the dialysis circuit) was applied, and the digital compression time necessary to
      achieve haemostasis at the puncture site was determined. After an initial period,
      when the regular heparin dose was replaced once weekly by fondaparinux, 0.05
      mg/kg, the pentasaccharide was administered for nine consecutive haemodialysis
      sessions. Peak anti-Xa activity increased from 0.61 +/- 0.14 microg/l after the
      first dose to 0.89 +/- 0.24 microg/l after dose 9 (P < 0.001), whereas
      predialysis anti-Xa activity steadily rose to 0.32 +/- 0.09 microg/l (P < 0.001).
      A sufficient but slightly less effective anticoagulation with a mean SQCS of 1.19
      +/- 0.71 (n = 121) was obtained by fondaparinux as compared with 0.65 +/- 0.58 (n
      = 60, P < 0.005) by 4,825 +/- 1,703 U of unfractionated heparin. Mean digital
      compression time rose slightly during fondaparinux from 23.7 +/- 7.4 minutes to
      24.8 +/- 7.5 minutes (P < 0.05) and, more important, six of the 12 patients
      reported minor bleeding problems during the interdialytic interval. Thus,
      fondaparinux can be used to prevent circuit clotting during haemodialysis;
      however, accumulation results in an interdialytic increase of anti-Xa activity.
      Therefore, fondaparinux should be reserved for patients requiring systemic
      anticoagulation on the days off dialysis.

PMID- 18064315
TI  - Profibrinolytic activity of the direct thrombin inhibitor melagatran and
      unfractionated heparin in platelet-poor and platelet-rich clots.
AB  - Anticoagulants have been shown to stimulate fibrinolysis principally via
      inhibition of thrombin-mediated activation of TAFI (thrombin activatable
      fibrinolysis inhibitor). Their profibrinolytic effect, however, may vary
      according to their mechanism of action and to the clot composition. We compared
      the fibrinolytic activity of the direct thrombin inhibitor melagatran with that
      of unfractionated heparin in platelet-poor (PPP) and platelet-rich (PRP) models
      consisting of tissue-factor-induced clots exposed to exogenous t-PA (25 ng/ml).
      In the PPP clot model, both heparin (0.1-0.6 U/ml) and melagatran (20-320 ng/ml)
      caused a concentration-dependent shortening of lysis time. However, when drug
      profibrinolytic activity (lysis ratio) was expressed in function of the aPTT
      prolongation (aPTT ratio), melagatran was more efficient than heparin. In the PRP
      clot model, melagatran displayed a fibrinolytic activity fairly comparable to
      that observed in PPP whilst heparin caused a modest reduction of lysis time only
      at the highest concentrations. Assay of thrombin and TAFIa generation in
      defibrinated plasma showed that the presence of platelets markedly reduced the
      ability of heparin, but not that of melagatran, to inhibit the formation of these
      enzymes. Altogether these data indicate that melagatran is more efficient than
      heparin in promoting fibrinolysis, particularly in plateletrich clots, and may
      thus grant a greater antithrombotic activity by enhancing thrombus dissolution.

PMID- 18064316
TI  - Role of haemorheological factors in patients with retinal vein occlusion.
AB  - Retinal vein occlusion (RVO) is an important cause of permanent visual loss.
      Hyperviscosity, due to alterations of blood cells and plasma components, may play
      a role in the pathogenesis of RVO. Aim of this case-control study was to evaluate
      the possible association between haemorheology and RVO. In 180 RVO patients and
      in 180 healthy subjects comparable for age and gender we analysed the whole
      haemorheological profile: [whole blood viscosity (WBV), erythrocyte deformability
      index (DI), plasma viscosity (PLV), and fibrinogen]. WBV and PLV were measured
      using a rotational viscosimeter, whereas DI was measured by a microcomputer
      assisted filtrometer. WBV at 0.512 sec(-1) and 94.5 sec(-1) shear rates as well
      as DI, but not PLV, were found to be significantly different in patients as
      compared to healthy subjects. At the logistic univariate analysis, a significant
      association between the highest tertiles of WBV at 94.5 sec(-1) shear rate (OR:
      4.91, 95% CI 2.95-8.17; p < 0.0001), WBV at 0.512 sec(-1) shear rate (OR: 2.31,
      95% CI 1.42-3.77; p < 0.0001), and the lowest tertile of DI (OR: 0.18, 95% CI
      0.10-0.32; p < 0.0001) and RVO was found. After adjustment for potential
      confounders, the highest tertiles of WBV at 0.512 sec(-1) shear rate (OR: 3.23,
      95% CI 1.39-7.48; p = 0.006), WBV at 94.5 sec(-1) shear rate (OR: 6.74, 95% CI
      3.06-14.86; p < 0.0001) and the lowest tertile of DI (OR: 0.20,95% CI 0.09-0.44,
      p < 0.0001) remained significantly associated with the disease. In conclusion,
      our data indicate that an alteration of haemorheological parameters may modulate
      the susceptibility to the RVO, by possibly helping to identify patients who may
      benefit from haemodilution.

PMID- 18064317
TI  - Venous thromboembolism in patients undergoing surgery: low rates of prophylaxis
      and high rates of filter insertion.
AB  - Patients who undergo surgery are at a high risk of developing venous
      thromboembolism (VTE). To further define the demographics, comorbidities, and
      risk factors of VTE in patients undergoing major surgery, we analyzed 1,375
      hospitalized non-orthopedic surgery patients in a prospective registry of 5,451
      patients with ultrasound confirmed deep vein thrombosis (DVT) from 183 hospitals
      in the United States. Extremity edema (67.9%), extremity discomfort (44.9%), and
      dyspnea (18.9%) were among the most common presenting symptoms among these
      surgical patients. Compared to medical patients, surgical patients presented with
      a more occult clinical picture and complained less often of extremity edema
      (67.9% vs. 73.7%; p = 0.0001), extremity discomfort (44.9% vs. 56.4%; p <
      0.0001), or difficulty walking (6.6% vs. 11.2%; p < 0.0001). Immobility within 30
      days of DVT diagnosis, prior hospitalization within 30 days of DVT diagnosis,
      presence of an indwelling central venous catheter, obesity (BMI>30 kg/m2), and
      previous smoking were the most commonVTE risk factors among surgical patients.
      Among surgical patients who developed DVT, some form of prophylaxis had been used
      in only 44%. Once diagnosed with DVT, surgical patients received IVC filters more
      often than medical patients (20.0% vs. 14.1%; p < 0.0001; adjusted OR = 1.49, 95%
      CI = 1.17-1.92; p < 0.001). In conclusion, VTE prophylaxis remains underutilized
      in surgical patients. The IVC filter utilization rate in surgical patients is
      significantly higher than in medical patients. Future studies should focus on
      devising mechanisms to improve implementation of prophylaxis and investigate the
      long-term safety and efficacy of IVC filters in surgical patients.

PMID- 18064318
TI  - Catechol-O-methyltransferase genotype is associated with plasma total
      homocysteine levels and may increase venous thrombosis risk.
AB  - A disturbed methylation has been proposed as a mechanism via which homocysteine
      is associated with diseases like vascular disease, neural tube defects and mental
      disorders. Catechol-O-methyltransferase (COMT) is involved in the S
      adenosylmethionine-dependent methylation of catecholamines and catecholestrogens
      and in this way contributes to homocysteine synthesis. COMT dysfunction has been
      related to schizophrenia and breast cancer. We hypothesized that COMT dysfunction
      by virtue of functional genetic polymorphisms may affect plasma total
      homocysteine (tHcy). Our primary objective was to study the association between
      common COMT polymorphisms and tHcy. Secondly, we evaluated these polymorphisms as
      a risk factor for recurrent venous thrombosis. We obtained genotype data from
      four polymorphisms in the COMT gene (rs2097603, rs4633, rs4680 [324G>A] and
      rs174699) from 401 population-based controls. We performed haplotype analysis to
      investigate the association between common haplotypes and tHcy. In addition, we
      assessed the rs4680 variant as a genetic risk factor in a case-control study on
      recurrent venous thrombosis (n = 169). We identified a common haplotype that was
      significantly associated with tHcy levels. This effect was largely explained by
      the rs4680 variant, resulting in an increase in tHcy of 10.4% (95% CI 0.01 to
      0.21, p = 0.03) for 324AA compared with 324GG subjects. Interestingly, we found
      that the 324AA genotype was more common in venous thrombosis patients (OR 1.61
      [95% CI 0.97 to 2.65], p = 0.06) compared to control subjects. We show that the
      COMT rs4680 variant modulates tHcy, and might be associated with venous
      thrombosis risk as well.

PMID- 18064319
TI  - Prediction of recurrent venous thromboembolism by measuring ProC Global.
AB  - In patients with venous thromboembolism (VTE) a laboratory assay that globally
      measures the overall thrombophilic tendency is not available. We hypothesized
      that determination of ProC((R)) Global, a plasma assay which tests the global
      function of the protein C pathway, could be used to stratify patients according
      to their risk of recurrent VTE. We prospectively followed 774 patients with first
      spontaneousVTE for a mean time of 52 months. ProC Global normalized ratio (NR)
      was measured in plasma by use of a commercially available assay based on
      activated partial thromboplastin time. Ninety-eight of the 774 patients had
      recurrentVTE. Patients with ProC Global NR > or = 0.75 had a relative risk of
      recurrence of 0.59 (95% CI 0.40-0.87) as compared with those with lower ratio.
      After four years, cumulative probability of recurrence was 8.6% in patients with
      ProC Global NR > or = 0.75 and 17.4% in patients with a lower ratio (p = 0.006).
      Patients with a high ProC Global NR have a low risk of recurrent VTE. ProC Global
      NR can be used to stratify patients with a first unprovoked VTE according to
      their risk of recurrence.

PMID- 18064321
TI  - APC resistance during the normal menstrual cycle.
AB  - Increased serum levels of endogenous as well as exogenous estrogen are regarded
      to be responsible for acquired activated protein C (APC) resistance. It was the
      objective of this study to evaluate whether the physiological increase in serum
      estradiol concentration during the normal menstrual cycle affects the
      individual's sensitivity to APC. Seventy-two women with normal menstrual cycles
      were included in the study. Blood samples for analysis of estradiol (E2),
      progesterone (P4) and APC resistance were drawn at two time points of the
      menstrual cycle (day 3-5 and day 22-25). Two methods of measuring APC resistance
      were used: the activated partial thromboplastin time (aPTT)-based assay and the
      endogenous thrombin potential (ETP)-based APC resistance test. Independent of the
      method used, no changes in APC resistance were found, even though the E2
      concentration increased significantly between the two menstrual phases. No
      correlations between E2 levels and APC resistance, P4 levels and APC resistance
      or changes in E2 concentrations and changes in APC resistance were detected. Ten
      women were carriers of the factor V(Leiden) mutation. Their baseline APC
      resistance was increased, but their response to elevated E2 during the menstrual
      cycle did not differ from that of non-carriers. In conclusion, our observations
      suggest that physiological differences in serum levels of estradiol and
      progesterone between the early follicular and the luteal phase in a normal
      menstrual cycle do not have any significant impact on the individual's
      sensitivity to APC.

PMID- 18064320
TI  - Risk stratification and heparin prophylaxis to prevent venous thromboembolism in
      pregnant women.
AB  - Women with a history of venous thromboembolism (VTE), thrombophilia or both may
      be at increased risk of thrombosis during pregnancy, but the optimal management
      strategy is not well defined in clinical guidelines because of limited trial
      data. A strategy of risk assessment and heparin prophylaxis was evaluated in
      pregnant women at increased risk of VTE. In a prospective trial (Efficacy of
      Thromboprophylaxis as an Intervention during. Gravidity [EThIG]), 810 pregnant
      women were assigned to one of three management strategies according to pre
      defined risk factors related to history of VTE and thrombophilic profile. Low
      risk women (group I), received 50-100 IU dalteparin/kg body weight/day for 14
      days postpartum, or earlier when additional risk factors occurred. Women at high
      (group II) or very high risk (group III) received dalteparin from enrollment
      until six weeks postpartum (50-100 IU and 100-200 IU/kg/day, respectively).
      Objectively confirmed, symptomatic VTE occurred in 5/810 women (0.6%; 95%
      confidence interval [CI], 0.2 to 1.5%) (group I, 0 of 225; II, 3/469; III,
      2/116). The rate of serious bleeding was 3.0% (95 % CI, 1.9 to 4.4%); 1.1% (95 %
      CI, 0.5 to 2.2%) was possibly dalteparin-related. There was no evidence of
      heparin-induced thrombocytopenia, one case of osteoporosis, and rates of
      miscarriage and stillbirth were similar to previous, retrospective studies. Risk
      stratified heparin prophylaxis was associated with a low incidence of
      symptomaticVTE and few clinically important adverse events. Antepartum heparin
      prophylaxis is, therefore, warranted in pregnant women with idiopathic thrombosis
      or symptomatic thrombophilia.

PMID- 18064322
TI  - Hypercoagulability after partial liver resection.
AB  - One concern of living donor liver transplantation remains the risk of morbidity
      and/or mortality for the donors, including the risk of postoperative thrombosis.
      We studied the coagulation changes after partial liver resection in l2 living
      donors and eight patients with non-malignant hepatic tumors (controls) and
      searched for potential predictive markers of thrombotic complications. Thrombosis
      (pulmonary embolism and portal vein thrombosis) developed in two donors and two
      controls. In donors and controls, we observed an early postoperative decrease in
      coagulation inhibitors protein C and antithrombin together with an increase in
      factor VIII and von Willebrand factor, which both persisted when prothrombin time
      had returned to normal. Dysregulation in the haemostatic system was confirmed by
      increased prothrombotic markers, with a 10- to 30-fold increase in thrombin
      antithrombin complexes and moderate increase(1.5- to 2.0-fold) in sP-Selectin. No
      difference between donors and controls was observed and the data were pooled for
      comparison of patients with (n = 4) versus without (n = 16) thrombosis. Thrombin
      antithrombin complexes were significantly higher in the thrombosis group, on day
      1 (28.8 vs. 13.5 microg/l, p = 0.027) and day 2 (52.3 vs. 9.3 microg/l, p =
      0.013). sP-selectin was also significantly higher in the thrombosis group on day
      2 (103 vs. 53 ng/ml, p = 0.044) and day 4 (116 vs. 58 ng/ml, p = 0.026) after
      surgery. Our study indicates that improvement of thromboprophylaxis in partial
      liver resection is needed. It also suggests that thrombin-antithrombin complexes
      and sP-selectin could serve as early biological predictors of thrombotic
      complications in the post-operative period.

PMID- 18064323
TI  - Disulfide bond disruption by a beta 3-Cys549Arg mutation in six Jordanian
      families with Glanzmann thrombasthenia causes diminished production of
      constitutively active alpha IIb beta 3.
AB  - Alpha IIb beta 3 integrin mediates platelet aggregation following its activation.
      Its absence or dysfunction causes Glanzmann thrombasthenia (GT), an inherited
      bleeding disorder that is rare worldwide but relatively frequent in several
      populations with high rates of consanguinity, including Arabs in Israel and
      Jordan. Cysteine residues in the beta 3 epidermal growth factor (EGF) domains are
      involved in alpha IIb beta 3 formation and activation. In this study we present a
      novel Cys549Arg mutation in beta 3 identified in six Jordanian families, which in
      the homozygous state is manifested by severe GT. The mutation is located in EGF-3
      of beta 3 predicting disruption of a conserved disulfide bond between Cys549 and
      Cys558. Haplotype analysis disclosed a common founder whose age estimate was 120
      150 years. Flow cytometry revealed 1-14% of normal alpha IIb beta 3 expression at
      the patients' platelet surface. The Cys549Arg or artificial Cys549Ser mutations
      were introduced into a beta 3 expression vector. Co-transfection of baby hamster
      kidney cells with normal or mutant beta 3 along with normal alpha IIb
      demonstrated reduced surface expression of alpha IIb beta 3 by both mutants. The
      mutants were constitutively active as demonstrated by 20-fold increased binding
      of the ligand-mimetic antibody PAC-1. Immunoblotting and immunoprecipitation
      experiments showed reduced beta 3 and alpha IIb beta 3 expression and a higher
      than normal ratio of pro-alpha IIb to mature alpha IIb. Immunofluorescence
      experiments showed that beta 3 and alpha IIb beta 3 were mostly retained in the
      endoplasmic reticulum. In conclusion, the novel ancestral mutation found in a
      cluster of Jordanian GT patients disrupts a conserved Cys549-Cys558 bond which
      results in reduced production of constitutively active alpha IIb beta 3.

PMID- 18064324
TI  - Enhanced platelet aggregation and activation under conditions of hypothermia.
AB  - The effects on platelet function of temperatures attained during hypothermia used
      in cardiac surgery are controversial. Here we have performed studies on platelet
      aggregation in whole blood and platelet-rich plasma after stimulation with a
      range of concentrations of ADP, TRAP, U46619 and PAF at both 28 degrees C and 37
      degrees C. Spontaneous aggregation was also measured after addition of saline
      alone. In citrated blood, spontaneous aggregation was markedly enhanced at 28
      degrees C compared with 37 degrees C. Aggregation induced by ADP was also
      enhanced. Similar results were obtained in hirudinised blood. There was no
      spontaneous aggregation in PRP but ADP-induced aggregation was enhanced at 28
      degrees C. The P2Y12 antagonist AR-C69931 inhibited all spontaneous aggregation
      at 28 degrees C and reduced all ADP-induced aggregation responses to small,
      reversible responses. Aspirin had no effect. Aggregation was also enhanced at 28
      degrees C compared with 37 degrees C with low but not high concentrations of TRAP
      and U46619. PAF-induced aggregation was maximal at all concentrations when
      measured at 28 degrees C, but reversal of aggregation was seen at 37 degrees C.
      Baseline levels of platelet CD62P and CD63 were significantly enhanced at 28
      degrees C compared with 37 degrees C. Expression was significantly increased at
      28 degrees C after stimulation with ADP, PAF and TRAP but not after stimulation
      with U46619. Overall, our results demonstrate an enhancement of platelet function
      at 28 degrees C compared with 37 degrees C, particularly in the presence of ADP.

PMID- 18064325
TI  - Determinants of platelet conjugate formation with polymorphonuclear leukocytes or
      monocytes in whole blood.
AB  - Following preliminary in-vitro experiments, platelet-leukocyte conjugates and
      their determinants were evaluated in citrated whole blood from 349 subjects (209
      women, age 16-92 years) randomly recruited from the general population. Platelet
      activation by ADP/collagen but not leukocyte stimulation by fMLP or LTB4 resulted
      in formation of platelet conjugates with PMN or monocytes. In the population
      study, mixed cell conjugates, platelet P-selectin and leukocyte CD11b were
      measured by flow cytometry both at baseline and after in-vitro stimulation with
      ADP/collagen. The latter significantly increased platelet conjugates with either
      PMN or monocytes, platelet P-selectin and leukocyte CD11b expression. Platelet
      count significantly correlated with platelet-PMN, platelet-monocyte conjugates
      and P-selectin both at baseline and upon stimulation. In all conditions, both
      conjugate levels correlated with each other, when adjusted for gender, age and
      platelet count. Age correlated with platelet-PMN conjugate numbers in basal and
      stimulated conditions and with basal P-selectin. ADP/collagen stimulation
      resulted in higher P-selectin and conjugates values in women. Among risk factors,
      a significant correlation was found between conjugate and glucose levels. In
      conclusion, the presence and formation in whole blood from a large population of
      platelet-leukocyte conjugates reflects primary platelet - but not leukocyte -
      activation and varies with gender, age, platelet count and blood glucose.

PMID- 18064327
TI  - Decreased platelet reactivity identified by whole blood flow cytometry in Fanconi
      anaemia patients.
AB  - Fanconi anaemia (FA) is a rare inherited chromosome instability disorder
      characterized by congenital anomalies and a high risk for bone marrow failure and
      cancer. Bleeding is a frequent complication in FA, leading to substantial
      morbidity and mortality. Thrombocytopenia is a major factor leading to this
      complication, but the bleeding tendency of FA patients often exceeds what one
      might expect based on their platelet counts. We therefore investigated if
      alterations of platelet function contribute to the bleeding tendency of FA
      patients. We assessed platelet function in 11 FA patients and 23 controls with
      whole blood flow cytometry. We analyzed the expression of platelet membrane
      glycoprotein receptors, reactivity of platelets to physiologic agonists and the
      proportion of young platelets. In FA patients platelet reactivity was decreased:
      Expression of P-selectin and binding of PAC-1 after stimulation with thrombin
      receptor activating peptide (TRAP) and adenosine diphosphate (ADP) were 15-70%
      lower than in controls. We found no or only minor differences of platelet
      glycoprotein receptor expression between groups. While the proportion of
      reticulated platelets was not different, the absolute number of reticulated
      platelets was markedly lower in FA patients. Our data show that FA is associated
      with reduced platelet reactivity, which may contribute to the high bleeding
      tendency in FA patients. Whole blood flow cytometry is a suitable method for
      analysis of platelet function in FA patients.

PMID- 18064326
TI  - Snake venom metalloproteinases, crotarhagin and alborhagin, induce ectodomain
      shedding of the platelet collagen receptor, glycoprotein VI.
AB  - Glycoprotein (GP)VI, that binds collagen, together with GPIb-IX-V which binds
      vonWillebrand factor, forms an adheso-signalling complex on platelets that
      initiates thrombus formation in haemostasis and thrombosis. In this study, we
      show that two snake venom metalloproteinases, crotarhagin and alborhagin, induce
      ectodomain shedding of GPVI by a mechanism that involves activation of endogenous
      platelet metalloproteinases. Alborhagin is a viper venom metalloproteinase from
      Trimeresurus albolabris, while crotarhagin is a previously undescribed toxin from
      the rattlesnake Crotalus horridus horridus ( approximately 60-kDa non-reduced and
      reduced). Like alborhagin, crotarhagin induces aggregation in human platelet-rich
      plasma (maximal activity, approximately 0.3 microg/ml). Aggregation of washed
      platelets was inhibited by soluble GPVI ectodomain expressed as an Fc-fusion
      protein, confirming crotarhagin targeted GPVI. Treating washed platelets with
      crotarhagin or alborhagin resulted in time-dependent loss of surface GPVI and the
      appearance of an approximately 55-kDa soluble GPVI fragment in supernatants.
      Crotarhagin also induced shedding in GPVItransfected RBL-2H3 cells. Crotarhagin
      induced shedding was metalloproteinase-dependent (inhibited by EDTA), but also
      blocked by inhibitors of GPVI signalling (Src kinase inhibitors, PP1 or PP2, or
      Syk inhibitor, piceatannol), indicating shedding required GPVI-dependent platelet
      activation. Together, the data suggest that the rattlesnake metalloproteinase,
      crotarhagin, and the viper toxin alborhagin, induce GPVI shedding by a mechanism
      involving activation of endogenous platelet metalloproteinases rather than direct
      cleavage of GPVI.

PMID- 18064328
TI  - Heterozygous loss of platelet glycoprotein (GP) Ib-V-IX variably affects platelet
      function in velocardiofacial syndrome (VCFS) patients.
AB  - Velocardiofacial syndrome (VCFS) is a common, phenotypically heterogeneous
      developmental disorder caused by an interstitial microdeletion within human
      chromosome 22q11. The deleted chromosomal region in >90% of VCFS patients
      includes the GPIb beta gene, encoding for one subunit of the platelet GPIb-V-IX
      receptor, which is critical for platelet adhesion under shear, and important in
      aggregation and thrombin-mediated activation. Complete loss of GPIb-V-IX due to
      autosomal recessive inheritance of two GPIb alpha, Ib beta or GP9 gene mutations,
      results in a severe bleeding disorder, Bernard-Soulier syndrome (BSS). In this
      study, twenty-one confirmedVCFS patients were analyzed for platelet morphological
      and functional alterations, resulting from the heterozygous loss of one GPIb beta
      gene allele. Compared to unaffected family members, VCFS patients showed a
      significant decrease in platelet count; VCFS platelet size and mean platelet
      volume were increased, but not as markedly as in BSS. As expected from obligatory
      heterozygotes for GPIb beta deficiency, VCFS patients showed reduced platelet
      GPIb-V-IX surface expression and total GPIb content, but with considerable
      variation between cases. Platelet function tested using the PFA-100 trade mark
      analyzer was impaired in 70% of patients. Platelet aggregation was reduced in
      response to a GPIb-dependent agonist, ristocetin, in 50% of VCFS patients, with
      35% showing a reduced response to thrombin receptor activating peptide. Genomic
      screening was performed to exclude mutations of the subunit genes, indicating
      that these platelet abnormalities were due to GPIb beta heterozygosity and not
      spontaneous BSS. In conclusion, many VCFS patients have in-vitro defects in
      platelet function that may increase their risk of bleeding during surgery.

PMID- 18064329
TI  - Alternative splicing of platelet cyclooxygenase-2 mRNA in patients after coronary
      artery bypass grafting.
AB  - Recently, we cloned from platelet mRNA a novel cyclooxygenase (COX)-2 splice
      variant, designated COX-2a, which is characterized by a partial deletion of exon
      5. Preliminary studies of mRNA distribution of COX-2 isoforms in platelets from
      coronary artery bypass grafting (CABG) patients showed a variable increase in COX
      2a mRNA expression after cardiac surgery. Thus, we assessed whether this variant
      may play a functional role in these patients. We report a marked (about 200-fold)
      increase in the expression of COX-2a mRNA after CABG. Evidence is presented that
      ribosomal frame-shifting may correct the coding sequence resulting in the
      expression of a full-length COX-2a protein. In addition, a reading frame
      corrected COX-2a mutant (COX-2a delta G) was generated by site-directed
      mutagenesis and expressed in COS-7 cells using an adenoviral expression system.
      However, COX-2a protein was not active in terms of prostaglandin formation. Thus,
      alternative mRNA splicing might represent an intriguing posttranscriptional
      mechanism to oppose a transcriptional activation of the COX-2 gene. Evolutionary,
      this mechanism may prevent COX-2-dependent thromboxane synthesis in the platelet,
      which would potentiate the likelihood of thrombosis; pharmacologically, this
      mechanism would prevent an aspirin-insensitive pathway of thromboxane formation.

PMID- 18064330
TI  - Effect of clopidogrel treatment on stress-induced platelet activation and
      myocardial ischemia in aspirin-treated patients with stable coronary artery
      disease.
AB  - Stress may counteract responses to antiplatelet drug treatment. We investigated
      if adding clopidogrel to aspirin treatment could attenutate stress-induced
      platelet activation and myocardial ischemia in patients with coronary artery
      disease (CAD). Thirty-one male patients with documented CAD-treated with aspirin
      (75-160 mg daily) were randomized to co-treatment with clopidogrel (n = 16) or
      placebo (n = 15). A symptom-limited exercise test and 48-hour (h) Holter
      monitoring were performed before and after two weeks of double-blind treatment.
      Platelet function was assessed by flow cytometry and impedance aggregometry in
      whole blood. Exercise-induced and ambulatory ischemia was assessed from
      electrocardiographic (ECG) recordings. Clopidogrel treatment inhibited ADP
      induced platelet P-selectin expression by 64% (22-87%), and attenuated the P
      selectin response to thrombin (p < 0.001), and platelet aggregation induced by
      low-dose collagen (p < 0.01). Exercise ( approximately 110W) increased heart rate
      similarly, and caused approximately 1.8 mm ST-segment depression both before and
      after treatment. Exercise caused platelet activation, i.e. increased circulating
      activated single platelets and platelet-platelet aggregates, enhanced the in
      vitro responsiveness to ADP or thrombin stimulation, and increased platelet
      leukocyte aggregation. Clopidogrel inhibited ADP-induced platelet activation to a
      similar relative degree at rest and during exercise, but did not attenuate the
      platelet activating effect of exercise. Addition of clopidogrel to aspirin
      treatment did not attenuate either ambulatory or exercise-induced ischemia. In
      conclusion, adding clopidogrel to aspirin treatment inhibited platelet activation
      by both ADP, thrombin and collagen in vitro, but did not influence the
      prothrombotic responses to exercise. Intensified antiplatelet treatment did not
      reduce ECG signs of either exercise-induced or ambulatory myocardial ischemia.

PMID- 18064331
TI  - The influence of established genetic variation in the haemostatic system on
      clinical restenosis after percutaneous coronary interventions.
AB  - Since activation of the haemostatic system is an important feature of the wound
      healing response triggered by arterial injury, variations in genes involved in
      thrombus formation may play a role in restenosis after percutaneous coronary
      interventions (PCI). Therefore, our aim was to examine the relationship between
      polymorphisms that are known to play a role in the haemostatic system and the
      risk of clinical restenosis in the GENetic DEterminants of Restenosis (GENDER)
      study, a multicenter prospective study design that enrolled 3,104 consecutive
      patients after successful PCI. Target vessel revascularization (TVR) was the
      primary endpoint. All patients were genotyped for six polymorphisms in the Factor
      II, Factor V, Factor VII and PAI-1 genes. The PAI-1 4G variant was associated
      with an increased risk of TVR. When compared to 5G/5G homozygotes, heterozygous
      patients were at higher risk for TVR (HR: 1.46, 95% CI: 1.05-2.03), whereas
      patients with the 4G/4G genotype had an even further increased risk (HR: 1.69,
      95% CI: 1.19-2.41). In contrast, the factor V 506Gln (factor V Leiden) amino acid
      substitution was associated with a decreased risk of TVR (HR: 0.41, 95% CI: 0.19
      0.86). Our findings indicate that polymorphisms in the factorV and PAI-1 genes
      may play a role in the process of restenosis.

PMID- 18064332
TI  - The significance of vasodilator-stimulated phosphoprotein for risk stratification
      of stent thrombosis.
AB  - Low-response to the P2Y12 adenosine diphosphate (ADP)-receptor antagonist
      clopidogrel was suggested to correspond to a higher incidence of stent thrombosis
      (ST). This prospective observational study assessed the capability of two
      platelet function assays, e.g. direct measurement of the phosphorylation status
      of vasodilator-stimulated phosphoprotein (VASP) and ADP-induced platelet
      aggregation for definition of the individual risk to develop ST. Ninety-nine
      patients with an elevated high risk to develop ST were enrolled. All patients
      received a dual antiplatelet therapy consisting of 100 mg aspirin and 75 mg
      clopidogrel during an observation period of six months. Flow cytometry of VASP
      phosphorylation and densitometrically-determined measurement of ADP-induced
      platelet aggregation was performed 72-96 hours after stent implantation. These
      data were related to angiographically confirmed ST. Nine patients suffered from
      angiographically confirmed ST (9.1%). The meanVASP-platelet reactivity indices
      (VASP-PRI) and values for ADP-induced platelet aggregation in the ST group were
      significantly higher (60.8 +/- 13.0 and 60.9 +/- 13.1, respectively) compared to
      patients without ST (41.3 +/- 14.0 and 50.8 +/- 14.4, P < 0.001 vs. 0.048,
      respectively). There was a fair correlation between both methods using non-linear
      regression analysis (r = 0.332). In a multivariate analysis, VASP was the only
      independent predictor of ST and was superior to previously identified
      angiographic parameters. Receiver- operator characteristic (ROC) curve analysis
      revealed a cut-off value for VASP-PRI of <48% to be associated with low risk of
      ST. In conclusion, determination of VASP phosphorylation is superior to
      conventional platelet aggregometry and angiographic parameters for assessing the
      risk of ST. Patients with a VASP-PRI >48% seem to have a significantly increased
      risk.

PMID- 18064333
TI  - Randomised comparison of G-CSF-mobilized peripheral blood mononuclear cells
      versus bone marrow-mononuclear cells for the treatment of patients with lower
      limb arteriosclerosis obliterans.
AB  - Previous studies have suggested that the lower limb arteriosclerosis obliterans
      (LASO) could be improved by autologous transplantation of either bone marrow
      mononuclear cells (BM-MNC) or G-CSF-mobilized peripheral blood mononuclear cells
      (M-PBMNC). However, the number of patients observed was very limited, and little
      information is available regarding comparison. The present randomised trial was
      designed to assess which is the better option. One hundred fifty patients with
      LASO were randomised to either group A (76 cases implanted with M-PBMNC) or group
      B (74 cases implanted with BM-MNC), and followed up for 12 weeks. Primary
      outcomes were safety and efficacy of treatment, based on ankle-brachial index
      (ABI) and rest pain, and analysis was per protocol. Significant improvement of
      the main clinical index was observed in both groups after transplantation. No
      transplantation-related complication was observed in either group. Comparative
      analysis revealed that at 12 weeks after cell implantation, improvement of ABI
      (difference 0.06 +/- 0.01; p < 0.0001), skin temperature (difference 0.55 +/-
      0.25; p = 0.028), and rest pain (difference -0.57 +/- -0.15;p < 0.0001) was
      significantly better in groupA patients than group B patients. However, there was
      no significant difference between two groups for pain-free walking distance,
      transcutaneous oxygen pressure, ulcers, and rate of lower limb amputation.
      Autologous transplantation of either M-PBMNC or BM-MNC significantly promotes
      improvement of limb ischaemia in patients with LASO. Comparative analysis
      indicated that M-PBMNC should be more practical in comparison with BM-MNC in the
      treatment of LASO.

PMID- 18064334
TI  - Coronary artery in-stent stenosis persists despite inhibition of the von
      Willebrand factor--collagen interaction in baboons.
AB  - Revascularization techniques, such as angioplasty and stent implantation,
      frequently lead to restenosis due to the formation of neointima after platelet
      activation and the concomitant release of various smooth muscle cell mitogenic
      and attractant factors. We here investigate whether inhibition of initial
      platelet adhesion after stent implantation can decrease neointima formation in a
      clinically relevant baboon model of in-stent stenosis using standard treatment
      with aspirin, clopidogrel and heparin. Inhibition of platelet adhesion was
      established by administration of the anti-von Willebrand factor (VWF) monoclonal
      antibody 82D6A3, which inhibits VWF binding to collagen. Administration of 82D6A3
      resulted in a complete inhibition of VWF binding to collagen during the first
      three days after stent implantation. No thrombocytopenia or prolongation of the
      bleeding time was observed. Our results show that the formation of neointima was
      not affected in the group of baboons where primary platelet adhesion was
      abolished with 82D6A3 when compared to the control group. Vascular injury scores
      were the same in both groups. Inhibition of platelet adhesion during the first
      three days after stenting, on top of standard treatment with aspirin, clopidogrel
      and heparin, had no effect on neo-intima formation in a baboon model of in-stent
      stenosis. During the last decade, attempts to translate seemingly effective
      therapies based on smaller animal experimentation to the clinic have consistently
      failed. This study, using a non-human primate model that more closely resembles
      the clinical situation, presents a model that may be of further clinical interest
      for studying the prevention of restenosis.

PMID- 18064335
TI  - Effect of oral contraceptives on thrombin generation measured via calibrated
      automated thrombography.
AB  - In a study population consisting of healthy men (n = 8), women not using oral
      contraceptives (OC) (n = 28) and women using different kinds of OC (n = 187) we
      used calibrated automated thrombography (CAT) in the absence and presence of
      added activated protein C (APC) to compare parameters that can be obtained from
      thrombin generation curves, i.e. lag time, time to peak, peak height and
      endogenous thrombin potential (ETP). Both with and without APC, plasmas of OC
      users exhibited the shortest lag time and time to peak, and the highest peak
      height and ETP. In the absence of APC none of these parameters differed between
      users of OC containing different progestogens. In contrast, in the presence of
      APC shorter lag times and time to peak, and higher peak height and ETP were
      observed in plasma of users of gestodene-, desogestrel-, drospirenone- and
      cyproterone acetate-containing OC than in plasma of users of levonorgestrel-
      containing OC. The ETP determined in the absence of APC (ETP(-APC)) had no
      predictive value for the APCsr (r = 0.11; slope 0.9 x 10(-3); 95% CI: -0.1 x 10(
      3) to 2.0 x 10(-3)) whereas the ETP measured in the presence of APC (ETP+APC)
      showed an excellent correlation with the APCsr (r = 0.95; slope 6.6 x 10(-3); 95%
      CI: 6.3 x 10(-3) to 6.9 x 10(-3)) indicating that the APCsr is entirely
      determined by the ETP+APC. In conclusion, OC use increases thrombin generation,
      but differential effects of second and third generation OCs on the protein C
      system likely determine the differences in the risk of venous thrombosis between
      these kinds of OC.

PMID- 18064336
TI  - Laboratory testing for heparin-induced thrombocytopenia is inconsistent in North
      America: a survey of North American specialized coagulation laboratories.
AB  - Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin
      therapy. As HIT is considered a clinico-pathologic entity, laboratory practices
      have an important role in diagnosing or excluding HIT. It was the objective of
      this study to assess the current status of laboratory testing for HIT in North
      America. An online survey consisting of 67 questions related to laboratory
      testing for HIT was developed by the North American Specialized Coagulation
      Laboratory Association (NASCOLA), and distributed to its 59 members. The survey
      included queries about HIT test ordering practices, HIT immunoassay and
      activation assays performed, and reporting practices. Data was collected from the
      44 NASCOLA laboratories who responded. Of these sites, 88% performed immunoassays
      for HIT, commonly using commercial assays. However, sites varied in practices
      related to use of controls, immunoglobulin class of antibody detected, and in
      result interpretation and reporting. Platelet activation assays for HIT were
      performed by 36% of sites, commonly using assays of serotonin release (50%) or
      heparin-induced platelet aggregation (43%). Sites varied in the use of washed
      platelets versus platelet-rich plasma, controls, and heparin concentrations. This
      survey is the first comprehensive assessment of patterns of practice in HIT
      testing among diagnostic coagulation laboratories in North America. We observed
      site-specific variability of testing methods encompassing all stages of testing,
      including pre-analytical handling, testing methodologies, and result
      interpretation and reporting. The variability in HIT platelet activation assay
      methods among institutions indicates a need for proficiency testing to assess
      assay performance, and for consensus guidelines on HIT laboratory testing.

PMID- 18064337
TI  - Interleukin 6 plasma levels predict with high sensitivity and specificity
      coronary stenosis detected by coronary angiography.
AB  - In recent years new biomarkers able to measure the coronary atherosclerotic
      burden have been investigated. The aim of the present study was: i) to measure
      plasma levels of four biomarkers: C reactive protein (CRP), soluble intercellular
      adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), 8-isosprostane (8-ISO), in a
      series of patients undergoing coronary angiography; ii) to assess the power of
      the biomarkers to predict critical coronary stenosis detected by angiography. The
      study population consisted of a group of 438 subjects undergoing coronary
      angiography; 160 patients with 0, 1, 2, or 3 critical vessels were selected, and
      biomarkers plasma levels were measured in plasma samples obtained before the
      procedure. The most predictive biomarker was then assayed in 120 patients with
      critical stenosis and 120 unmatched patients without stenosis. CRP, sICAM-1, IL-6
      and 8-ISO plasma levels increased with the number of diseased vessels. All
      biomarkers were good predictors of critical stenosis (receiver-operator-curve
      [ROC] areas; CRP = 0.880, IL-6 = 0.936, sICAM-1 = 0.907, 8-ISO = 0.873). IL-6 was
      confirmed in an expanded sample of 240 subjects to be the best predictor with a
      ROC area = 0.959. With a threshold of 3.6 ng/l, a 100% sensitivity (120/120) and
      a 90% specificity (108/120) was observed. In conclusion, IL-6, sICAM-1, CRP and 8
      ISO are predictive of CAD. IL-6 predicts critical coronary stenosis with the
      highest sensitivity and specificity.

PMID- 18064338
TI  - Autoimmune thrombocytopenia in two patients with Sneddon's Syndrome.

PMID- 18064339
TI  - Ischemic brain damage triggers overt disseminated intravascular coagulation in a
      young woman with cerebral venous sinus thrombosis.

PMID- 18064340
TI  - Bilateral axillary vein thrombosis in a young patient with lupus anticoagulant
      and clavicular bone spurs.

PMID- 18064342
TI  - A case of very late stent thrombosis at high altitude.

PMID- 18064341
TI  - Successful outcome in a pregnant woman with homozygous antithrombin deficiency.

PMID- 18064343
TI  - A role for von Willebrand factor in Streptococcus sanguis-induced platelet
      activation.

PMID- 18064344
TI  - Once-daily fondaparinux monotherapy without warfarin for long-term treatment of
      venous thromboembolism.

PMID- 18064345
TI  - Comparison of two laboratory assays for the investigation of fibrin gel porosity.

PMID- 18064346
TI  - Fondaparinux as an alternative therapy in heparin-induced delayed-type
      hypersensitivity skin lesions.

PMID- 18064347
TI  - Toll-like receptors are key participants in innate immune responses.
AB  - During an infection, one of the principal challenges for the host is to detect
      the pathogen and activate a rapid defensive response. The Toll-like family of
      receptors (TLRs), among other pattern recognition receptors (PRR), performs this
      detection process in vertebrate and invertebrate organisms. These type I
      transmembrane receptors identify microbial conserved structures or pathogen
      associated molecular patterns (PAMPs). Recognition of microbial components by
      TLRs initiates signaling transduction pathways that induce gene expression. These
      gene products regulate innate immune responses and further develop an antigen
      specific acquired immunity. TLR signaling pathways are regulated by intracellular
      adaptor molecules, such as MyD88, TIRAP/Mal, between others that provide
      specificity of individual TLR- mediated signaling pathways. TLR-mediated
      activation of innate immunity is involved not only in host defense against
      pathogens but also in immune disorders. The involvement of TLR-mediated pathways
      in auto-immune and inflammatory diseases is described in this review article.

PMID- 18064348
TI  - The threat from creationism to the rational teaching of biology.
AB  - Most biologists outside the USA and a few other countries, like Australia and
      Canada, are under the impression that the threat to the teaching of biology
      represented by creationism does not concern them directly. This is unfortunately
      no longer true: the recent growth of creationism, especially in its pseudo
      scientific manifestation known as "intelligent design", has been obvious in
      several countries of Western Europe, especially the UK, Germany and Poland, and
      it is beginning to be noticeable in Brazil, and maybe elsewhere in Latin America.
      The problem is complicated by the fact that there are not just two possibilities,
      evolution and creationism, because creationism comes in various incompatible
      varieties. Turkey is now a major source of creationist propaganda outside the
      USA, and is especially significant in relation to its influence on Muslim
      populations in Europe. The time for biologists to address the creationist threat
      is now.

PMID- 18064349
TI  - Stimulus specificity in the acquisition and extinction of conditioned taste
      aversion.
AB  - An experiment evaluated whether the acquisition and extinction of conditioned
      taste aversion in the rat is stimulus-specific by testing the degree of response
      transfer between sweet and salty tastes. Animals in the paired-same and paired
      different groups received a presentation of a gustatory CS and a cyclophosphamide
      injection US. Nonconditioned control groups received unpaired CS /US
      presentations or the CS followed by a vehicle injection. Taste avoidance was
      evaluated in three nonreinforced test sessions. In the paired-same, unpaired and
      vehicle groups, all test sessions were conducted with the same flavor as
      originally used in training, whereas the paired-different group was tested with a
      novel flavor on the first and second sessions and with the originally trained
      flavor in last session. Stimulus specific acquisition was apparent in the first
      test session, when the animals in the group paired-same exhibited lower fluid
      intake than the other three groups. Evidence of specificity of extinction was
      apparent in the last test session, when animals in the group paired-different
      exhibited lower fluid intake than the other three groups. These results provide
      further evidence of stimulus specificity in acquisition and extinction of
      conditioned taste aversion, supporting the associative interpretation of these
      phenomena.

PMID- 18064350
TI  - The ingestion of a Nectandra membranacea extract changes the bioavailability of
      technetium-99m radiobiocomplex in rat organs.
AB  - The radiobiocomplexes labeled with technetium-99m (Tc-99m) have been widely used
      in nuclear medicine in single photon emission computed tomography and in basic
      research. The aim of this study was to assess the influence of a Nectandra
      membranacea extract on the bioavailability of the sodium pertechnetate
      (Na(99m)TcO(4)) radiobiocomplex in rat organs. The animals were treated with a N.
      membranacea extract (30 mg/ ml), for 6 days. Na(99m)TcO(4) was injected, the
      organs were isolated and weighed, and the radioactivity was determined in each
      organ (%ATI/organ). The %ATI/organ was divided by the mass of each organ to
      calculate the %ATI/g. A significant increase of the %ATI/organ of Na(99m)TcO(4)
      was observed in muscle and thyroid as well as in the %ATI/g in the heart, kidney
      and thyroid. These findings could result from the interaction between components
      of the plant extract and the radiobiocomplex which may influence the uptake
      Na(99m)TcO(4) in rat organs. Therefore, precaution is suggested in the
      interpretation of nuclear medicine results in patients using this herb.

PMID- 18064351
TI  - Changes in PEP carboxylase, rubisco and rubisco activase mRNA levels from maize
      (Zea mays) exposed to a chronic ozone stress.
AB  - We quantified the ozone impact on levels of Zea mays L. cv. Chambord mRNAs
      encoding C4-phosphoenolpyruvate carboxylase (C4-PEPc), ribulose-l,5-bisphosphate
      carboxylase/oxygenase small and large subunits (Rubisco-SSU and Rubisco-LSU,
      respectively) and Rubisco activase (RCA) using real-time RT-PCR. Foliar pigment
      content, PEPc and Rubisco protein amounts were simultaneously determined. Two
      experiments were performed to study the ozone response of the 5th and the 10th
      leaf. For each experiment, three ozone concentrations were tested in open-top
      chambers: non-filtered air (NF, control) and non-filtered air containing 40 (+40)
      and 80 nL L-1 (+80) ozone. Regarding the 5th leaf, +40 atmosphere induced a loss
      in pigmentation, PEPc and Rubisco activase mRNAs. However, it was unable to
      notably depress carboxylase protein amounts and mRNAs encoding Rubisco. Except
      for Rubisco mRNAs, all other measured parameters from 5th leaf were depressed by
      +80 atmosphere. Regarding the 10th leaf, +40 atmosphere increased photosynthetic
      pigments and transcripts encoding Rubisco and Rubisco activase. Rubisco and PEPc
      protein amounts were not drastically changed, even if they tended to be
      increased. Level of C4-PEPc mRNA remained almost stable. In response to +80
      atmosphere, pigments and transcripts encoding PEPc were notably decreased.
      Rubisco and PEPc protein amounts also declined to a lesser extent. Conversely,
      the level of transcripts encoding both Rubisco subunits and Rubisco activase that
      were not consistently disturbed tended to be slightly augmented. So, the present
      study suggests that maize leaves can respond differentially to a similar ozone
      stress.

PMID- 18064352
TI  - Antioxidant effect of 5-amino salicylic acid on copper-mediated LDL oxidation.
AB  - The antioxidant effect of 5-Aminosalicylic acid (5-ASA) on copper-mediated LDL
      oxidation was followed either by the emitted chemiluminiscence (CL) or by UV-vis
      spectroscopy. 5-ASA addition extends the lag phase in a concentration-dependent
      manner without changes in the rate of the process in the autoaccelerated phase.
      The antioxidant behavior of 5-ASA was very similar to that of Trolox, a very
      efficient water soluble antioxidant. The copper-binding capacity of 5-ASA was
      evaluated by UV-visible spectroscopy. The addition of copper to a 5-ASA solution
      increases the absorbance at 332 nm and generates a new band at 298 nm. These
      changes in the UV-vis spectra indicate formation of a complex between 5-ASA and
      copper. However, LDL protection by 5-ASA is unrelated to its copper chelating
      capacity.

PMID- 18064353
TI  - Species composition and seasonal succession of saprophagous calliphorids in a
      rural area of Cordoba: Argentina.
AB  - During 2004, four experiments were carried out, one each season, in order to
      determine the species composition and seasonal dynamics of Calliphoridae in a
      rural area of Cordoba (Argentina). Two pigs (Sus scrofa L.), weighing
      approximately 8 Kg each, were used in each experiment. They were killed with a
      blow to the head and immediately placed in a variant of the Schoenly et al.
      (1991) trap. One pig was exposed in the shade and the other one under direct
      sunlight. The insect fauna was collected daily during the four first weeks and
      every two or three days thereafter. A total of 16.609 adults of Calliphoridae
      were collected, and later on identified as one of the following seven species:
      Chrysomya albiceps (Wiedemann), Chrysomya megacephala (Fabricius), Phaenicia
      sericata (Meigen), Phaenicia eximia (Wiedemann), Cochliomyia macellaria
      (Fabricius), Sarconesia chlorogaster (Wiedemann) and Calliphora vicina Robineau
      Desvoidy. C. albiceps was the dominant species in summer, autumn and spring,
      being replaced in winter by C. vicina, S. chlorogaster and P. sericata. The
      analysis of the seasonal distribution of the species revealed that the greater
      incidences are in the months of summer, autumn and spring.

PMID- 18064355
TI  - The chromatin structure of the lysozyme GAS41 origin of DNA replication changes
      during the cell cycle.
AB  - We used a rapid and simple protocol using lysolecithin for mapping HS sites in
      vivo. The protocol is based on partial digestion with DNase I of exponentially
      growing cells following permeabilization by short treatment with lysolecithin.
      Using this protocol, we analyzed the chromatin structure of the region
      surrounding two overlapping elements, an origin of bidirectional DNA replication
      and the GAS41 promoter, in chicken myelomonocytic HD11 cells arrested in G0, G1
      and S phases as well as at the G1/S border. The results show that the chromatin
      of this region became more nuclease sensitive when cells were arrested in G1
      phase and that this change in chromatin structure was reversible after the cells
      began to enter S phase.

PMID- 18064354
TI  - Construction of an immunotoxin by linking a monoclonal antibody against the human
      epidermal growth factor receptor and a hemolytic toxin.
AB  - Hybrid molecules obtained through conjugation of monoclonal antibodies and toxins
      constitute an approach under exploration to generate potential agents for the
      treatment of cancer and other diseases. A frequently employed toxic component in
      the construction of such immunotoxins is ricin, a plant toxin which inhibits
      protein synthesis at ribosomal level and so requires to be internalized by the
      cell. A hemolytic toxin isolated from the sea anemone Stichodactyla helianthus,
      which is active at the cell membrane level, was linked through a disulfide bond
      to the anti-epidermal growth factor receptor monoclonal antibody ior egf/r3. The
      resulting immunotoxin did not exhibit hemolytic activity except under reducing
      conditions. It was toxic for H125 cells that express the human epidermal growth
      factor receptor, but non-toxic for U1906 cells that do not express this receptor.

PMID- 18064356
TI  - Interplay between the morphometry of the lungs and the mode of locomotion in
      birds and mammals.
AB  - We studied the lung diffusion parameters of two species of birds and two species
      of mammals to explore how structural and functional features may be paralleled by
      differences in life style or phylogenetic origin. We used two fast-flying species
      (one mammal and one bird), one running mammal and one bird species that flies
      only occasionally as models. The harmonic mean thickness of the air-blood barrier
      was very thin in the species we studied. An exception was the Chilean tinamou
      Notoprocta perdicaria, which only flies occasionally. It showed an air-blood
      barrier as thick as that of flightless Galliformes. We found that the respiratory
      surface density was significantly greater in flying species compared to running
      species. The estimated values for the oxygen diffusion capacity, DtO2 follow the
      same pattern: the highest values were obtained in the flying species, the bat and
      the eared dove. The lowest value was in N. perdicaria. Our findings suggest that
      the studied species show refinements in their morphometric lung parameters
      commensurate to their energetic requirements as dictated by their mode of
      locomotion, rather than their phylogenetic origin. The air-blood barrier appears
      to be thin in most birds and small mammals, except those with low energetic
      requirements such as the Chilean tinamou. In the species we studied, the
      respiratory surface density appears to be the factor most responsive to the
      energetic requirements of flight.

PMID- 18064357
TI  - Fluorescent serum and urinary advanced glycoxidation end-products in non-
      diabetic subjects.
AB  - INTRODUCTION: Advanced glycoxidation end-products (AGEs) are involved in age
      related conditions and diabetic complications. Diet intake contributes to their
      circulating concentrations. AIM: To measure serum and urinary AGEs in non
      diabetic volunteers and relate their concentration to body composition, blood
      chemistry and dietary ingestion. METHODS: We studied 41 adult men (31 middle-aged
      adults and 10 elderly). A nutritional assessment including a dietary recall
      designed for detection of AGE ingestion (specifically carboxymethyl-lysine(CML)),
      and anthropometric measurements were performed. Also serum lipoproteins, insulin,
      glucose, leptin and C reactive protein (CRP). AGEs were measured in serum and
      urine samples using size exclusion chromatography and flow injection assay (FIA);
      the technical procedures were first employed in 11 heterogeneous diabetics, as
      positive controls for this methodology. RESULTS: Serum and urinary chromatograms
      indicated that areas under the curve were not different in younger compared with
      elderly adults. AGEs did not correlate with dietary intake, body composition, nor
      metabolic parameters, however they correlated significantly with renal function
      and CRP concentration. DISCUSSION: In these non-diabetic volunteers, with low CML
      intake, serum and urinary concentration of AGEs were not related to dietary
      intake. AGEs were related to renal function and CRP, but not to body composition,
      lipoproteins, insulin and glucose.

PMID- 18064358
TI  - Genital sensory stimulation shifts estradiol intraoviductal signaling from
      nongenomic to genomic pathways, independently from prolactin surges.
AB  - Estradiol (E2) accelerates oviductal egg transport through nongenomic pathways
      involving oviductal protein phosphorylation in non-mated rats, and through
      genomic pathways in mated rats. Here we investigated the ability of cervico
      vaginal stimulation (CVS) to switch the mode of action of E2 in the absence of
      other male-associated components. Pro-estrous rats were subjected to CVS with a
      glass rod and 12 hours later were injected subcutaneously with E2 and
      intrabursally with the RNA synthesis inhibitor Actinomycin D or the protein
      phosphorylation inhibitor H-89. The number of eggs in the oviduct, assessed 24 h
      later, showed that Actinomycin D, but not H-89 blocked the E2-induced egg
      transport acceleration. This clearly indicates that CVS alone, without other
      mating-associated signals, is able to shift E2 signaling from nongenomic to
      genomic pathways. Since mating and CVS activate a neuroendocrine reflex that
      causes iterative prolactin (PRL) surges, the involvement of PRL pathway in this
      phenomenon was evaluated. Prolactin receptor mRNA and protein expression in the
      rat oviduct was demonstrated by RT-PCR and Western blot, but their levels were
      not different on day 2 of the cycle (C2) or pregnancy (P2). Activated ST AT 5a/b
      (phosphorylated) was detected by Western blot on P2 in the ovary, but not in the
      oviduct, showing that mating does not stimulate this PRL signalling pathway in
      the oviduct. Other rats subjected to CVS in the evening of pro-estrus were
      treated with bromoergocriptine to suppress PRL surges. In these rats, H-89 did
      not block the E2-induced acceleration of egg transport suggesting that PRL surges
      are not essential to shift E2 signaling pathways in the oviduct. We conclude that
      CVS is one of the components of mating that shifts E2 signaling in the oviduct
      from nongenomic to genomic pathways, and this effect is independent of PRL surges
      elicited by mating.

PMID- 18064359
TI  - XV-2c and KM.19 haplotype analysis in Chilean patients with cystic fibrosis and
      unknown CFTR gene mutations.
AB  - Cystic fibrosis (CF) is caused by mutations in the CFTR gene. More than 1600
      mutations have been described, with frequencies that differ worldwide according
      to the ethnic origin of patients. A small group of mutations are recurrent on
      several populations. It has been shown that they each tend occur on specific
      chromosome 7 haplotypes, supporting the notion of a single origin for them. Less
      than 50% of mutations in Chilean patients have been identified to date. To
      indirectly assess the possible presence of a predominant founder mutation in the
      remaining unknown alleles, we evaluated 2 polymorphic markers, XV-2c and KM.19,
      tightly linked to the CFTR locus. The study was done in Chilean CF patients with
      unknown or deltaF508 (DeltaF508) CFTR mutations and their haplotypes were
      compared to affected family-based controls. DeltaF508 showed marked linkage
      disequilibrium with XV-2c/KM.19 haplotype B, with 90% of alleles on that
      haplotype. There was no difference in haplotype distribution between unknown
      mutations and normal controls. These results support a European origin for
      DeltaF508 alleles in Chilean patients, and make unlikely the presence of a
      predominant founder mutation in the so-far unknown alleles.

PMID- 18064360
TI  - Evaluation of the role of the endoplasmic reticulum-Golgi transit in the
      biogenesis of peroxisomal membrane proteins in wild type and peroxisome
      biogenesis mutant CHO cells.
AB  - Peroxisomes are thought to be formed by division of pre-existing peroxisomes
      after the import of newly synthesized proteins. However, it has been recently
      suggested that the endoplasmic reticulum (ER) provides an alternative de novo
      mechanism for peroxisome biogenesis in some cells. To test a possible role of the
      ER-Golgi transit in peroxisome biogenesis in mammalian cells, we evaluated the
      biogenesis of three peroxisomal membrane proteins (PMPs): ALDRP
      (adrenoleukodystrophy related protein), PMP70 and Pex3p in CHO cells. We
      constructed chimeric genes encoding these PMPs and green fluorescent protein
      (GFP), and transiently transfected them to wild type and mutant CHO cells, in
      which normal peroxisomes were replaced by peroxisomal membrane ghosts. The
      expressed proteins were targeted to peroxisomes and peroxisomal ghosts correctly
      in the presence or absence of Brefeldin A (BFA), a drug known to block the ER
      Golgi transit. Furthermore, low temperature did not disturb the targeting of
      Pex3p-GFP to peroxisomes. We also constructed two chimeric proteins of PMPs
      containing an ER retention signal "DEKKMP": GFP-ALDRP-DEKKMP and myc- Pex3p
      DEKKMP. These proteins were mostly targeted to peroxisomes. No colocalization
      with an ER maker was found. These results suggest that the classical ER-Golgi
      pathway does not play a major role in the biogenesis of mammalian PMPs.

PMID- 18064361
TI  - The CK1 gene family: expression patterning in zebrafish development.
AB  - Protein kinase CK1 is a ser/thr protein kinase family which has been identified
      in the cytosol cell fraction, associated with membranes as well as in the
      nucleus. Several isoforms of this gene family have been described in various
      organisms: CK1alpha, CK1beta, CK1delta, CK1epsilon and CK1gamma. Over the last
      decade, several members of this family have been involved in development
      processes related to wnt and sonic hedgehog signalling pathways. However, there
      is no detailed temporal information on the CK1 family in embryonic stages, even
      though orthologous genes have been described in several different vertebrate
      species. In this study, we describe for the first time the cloning and detailed
      expression pattern of five CK1 zebrafish genes. Sequence analysis revealed that
      zebrafish CK1 proteins are highly homologous to other vertebrate orthologues.
      Zebrafish CK1 genes are expressed throughout development in common and different
      territories. All the genes studied in development show maternal and zygotic
      expression with the exception of CK1epsilon. This last gene presents only a
      zygotic component of expression. In early stages of development CK1 genes are
      ubiquitously expressed with the exception of CK1epsilon. In later stages the five
      CK1 genes are expressed in the brain but not in the same way. This observation
      probably implicates the CK1 family genes in different and also in redundant
      functions. This is the first time that a detailed comparison of the expression of
      CK1 family genes is directly assessed in a vertebrate system throughout
      development.

PMID- 18064362
TI  - [Bilateral inferior petrosal sinus sampling in the differential diagnosis of ACTH
      dependent Cushing's syndrome].
AB  - BACKGROUND: The features of pituitary ACTH-dependent Cushing syndrome are often
      indistinguishable from those of occult ectopic ACTH-dependent Cushing syndrome
      (CS). AIM: To assess the diagnostic accuracy of bilateral inferior petrosal sinus
      sampling (BIPSS) in the differential diagnosis of ACTH-dependent Cushing's
      syndrome as compared with ACTH levels and the overnight high dose dexamethasone
      suppression test (HDDST). MATERIAL AND METHODS: Retrospective review of medical
      records of 23 patients (aged 19 to 63 years, 16 women) with surgically proven CS,
      20 pituitary microadenomas (CD) and 3 with occult ectopic ACTH secretion (EAS).
      RESULTS: No tumor was identifiable by imaging techniques. Mean plasma ACTH values
      were higher in patients with EAS than in CD (103+/- 110.2 and 73.1+/-41.98 pg/mL
      respectively, p=NS). Three patients with EAS and 3 patients with CD did not
      suppress cortisol with the HDDST. The sensitivity of the test was 86% and the
      specificity 100%. To improve the diagnostic outcome of BIPSS, an stimulation with
      Desmopressin (9 fig i.v) was performed in 9 patients. The threshold for a
      pituitary source, was defined as an inferior petrosal sinus to peripheral ACTH
      basal and post Desmopression ratio >2. BIPSS was successfully carried out in 22
      patients and no complications occurred. In 6 patients BIPSS failed to meet the
      threshold criteria. In 3 patients, bronchial carcinoid tumors which proved to
      synthesize ACTH, were removed. The diagnostic sensitivity of BIPSS greatly
      improved from 86% to 100% after Desmopressin stimulation. BIPSS accurately
      predicted the inverted exclamation markateralization of the microadenoma in 8 of
      12 patients (66%). CONCLUSIONS: The combination of Desmopressin stimulation with
      BIPSS was useful for the differential diagnosis of ACTH-dependent Cushing's
      Syndrome. However, the preoperative location of pituitary microadenomas was
      poorly predicted by BIPSS.

PMID- 18064363
TI  - [Mutations in gyrA and gyrB genes among strains of Gram-negative bacilli isolated
      from Chilean hospitals and their relation with resistance to fluoroquinolones].
AB  - BACKGROUND: A progressive frequency of resistance to fluoroquinolones is observed
      among Gram-negative bacilli. AIM: To investigate the mechanism of resistance to
      fluoroquinolones mediated by mutations affecting gyrA and gyrB genes in strains
      of Gram negative baculi isolated from CMean hospitals. MATERIAL AND METHOD:
      Minimal inhibitory concentration of fluoroquinolones was determined in 91
      randomly selected nalidixic acid-resistant strains of Escherichia coli,
      Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa,
      isolated from hospitals of 12 Chilean cities. Quinolone resistance determining
      region (QRDR) was amplified by PCR and mutations were determined by restriction
      fragment length polymorphism (RFLP) and DNA sequencing. RESULTS: Strains with
      mutation in codon 83 of gyrA showed decreased susceptibility to ciprofloxacin
      with MICs ranging from 0.25 to 1024 fig/ml. The sequencing of PCR products for
      gyrA indicated amino acid changes in the QRDR region. One strain ofE. coli
      presented a double mutation, in codon 83 Ser to Leu as well as in codon 87 Asp to
      Asn. In strains ofK. pneumoniae, however, the change of codon 83 was Ser to Tyr,
      in A. baumannii was Ser to Leu and in P. aeruginosa was Thr to He. No strains
      with mutations affecting gyrB were found. CONCLUSIONS: Mutations in codon 83 of
      gyrA is a frequent genetic event involved in the mechanism leading to decreased
      susceptibility to fluoroquinolone in strains of Gram-negative bacilli.

PMID- 18064364
TI  - [Clinical features and survival of Chilean patients with multiple myeloma].
AB  - BACKGROUND: Mortality rate records are the only data available in Chile about the
      prognosis of patients with multiple myeloma (MM). AIM: To characterize clinical
      features, survival rate and factors related to mortality in cases with MM treated
      in six large medical centers in Chile. MATERIAL AND METHOD: Retrospective
      analysis of demographic data, clinical features and survival rate records of
      patients with MM, collected between 1998 and 2002. Survival curves were generated
      and a multivariate analysis of factors associated to early mortality was carried
      out. RESULTS: Data from 245 patients aged 38 to 95 years (129 women) was
      collected. Fifty two percent had an IgG myeloma, 25% had and IgA and 6.1% had
      light chains myeloma. According to Durie and Salmon staging system, 8,2% were in
      Stage 112.6% in Stage II, 60.5% in Stage III and in 18.8% the information about
      staging was not available. Fifty percent had an hemoglobin level below 10 g/dL,
      30% had a serum creatinine over 2 mg/dL and 28% had a serum calcium level over
      10.5 mg/dL. Median survival was 33 months. Twenty percent of patients died within
      the first six months after diagnosis (early mortality). Predictive factors for
      early mortality were male sex, thrombocytopenia, anemia, renal failure,
      hypercalcemia, a beta2-microglobulin >5.5 mg/L and a serum albumin level <3.5
      g/dL. There was a correlation between the number of bad prognosis factors present
      and the probability of early mortality. CONCLUSIONS: This group of Chilean
      patients with MM presented a short survival time, and 20% died within the first
      six months after diagnosis. More than a half of cases were diagnosed at an
      advanced stage (Durie and Salmon Stage III). Several factors were associated to
      early mortality, two of which (beta 2-microglobulin and serum albumin), are
      included in the new International Staging System for MM.

PMID- 18064365
TI  - [Isolation of periodontal bacteria from blood samples and atheromas in patients
      with atherosclerosis and periodontitis].
AB  - BACKGROUND: Periodontitis is a common oral disease produced by bacterial species
      that reside in the subgingival plaque. These microorganisms have been associated
      to atherosclerosis and it is suggested that periodontitis is a cardiovascular
      risk factor. AIM: To isolate periodontal bacteria from blood and atheroma
      samples, from patients with atherosclerosis and periodontitis. MATERIAL AND
      METHODS: Twelve patients with periodontitis and a clinical diagnosis of
      atherosclerosis and 12 patients with periodontitis but without atherosclerosis
      were studied. Blood samples were obtained immediately before and after scaling
      and root planing. The samples were incubated in aerobic and anaerobic conditions.
      One week after scaling, atheromatous plaques were obtained during endarterectomy
      in the 12 patients with atherosclerosis. These were homogenized and cultured for
      aerobic and anaerobic bacteria. Microorganisms were identified by means ofPCR.
      RESULTS: Five patients with and two without atherosclerosis, had bacteremia after
      scaling and root planing. Bacterial species isolated from blood samples were the
      same found in periodontic pockets. Four atheromatous plaques of patients with
      bacteremia yielded positive cultures. The isolated bacteria were the same found
      in blood samples and periodontal pockets. CONCLUSIONS: Bacteremia occurred in
      seven of 24 patients after scaling and root planing. In four patients, the same
      species found in periodontic pockets and blood cultures were detected in
      atherosclerotic plaques obtained one week after the dental procedure.

PMID- 18064366
TI  - [Association of hyperinsulinemia with left ventricular hypertrophy and diastolic
      dysfunction in patients with hypertension].
AB  - BACKGROUND: Hypertension is the main independent cardiovascular risk factor.
      However, there are additional factors that induce organic damage. AIM: To assess
      the association between hyperinsulinemia, ventricular hypertrophy and left
      ventricular diastolic function. PATIENTS AND METHODS: Seventy-four patients aged
      30 to 65 years, with mild or moderate systemic hypertension, with overweight or
      mild obesity and normal glucose tolerance curve (GTC), were studied. Serum
      insulin was measured during GTC. The maximum levels of insulin and glucose were
      observed 60 minutes after the oral glucose load and they were expressed as rG/1.
      Patients were stratified in three groups according to their glucose and insulin
      fasting levels (I0) and post-glucose challenge levels (rG/I): Group 1
      (normoinsulinemic patients) I0 <17 mU/mL and rG/I >2 (2.45+0.4). Group 2 (post
      prandial hyperinsulinemic patients) I0 <17 mU/mL and rG/I <2> 1 (1.34+0.3). Group
      3 (persistently hyperinsulinemic patients) I0 >17 mU/mL and <1 (0.7+0.3). Left
      ventricular mass and its diastolic function were measured by Doppler
      echocardiography. RESULTS: No differences in blood pressure or age were observed
      between groups. There was a negative correlation between ventricular mass and
      rG/1 (r =-0.282, p =0.015). Left ventricular diastolic dysfunction was
      significantly more deteriorated in group 3, as compared with group 1 (p <0.001
      ANOVA). There was a significant correlation between g/GI and diastolic
      dysfunction (r =0.232 p =0.047). CONCLUSIONS: Fasting, post challenge
      hyperinsulinemia and a rG/I <1 are associated with higher ventricular mass and
      left ventricular diastolic dysfunction, independent of blood pressure and age.

PMID- 18064367
TI  - [Hiccup: review of 24 cases].
AB  - BACKGROUND: Although common and usually benign, hiccups can be an extremely
      uncomfortable disease. There is not much information about persistent and
      refractory hiccups. AIM: To report clinical features of patients admitted in a
      hospital due to hiccup. PATIENTS AND METHODS: A retrospective study and
      prospective follow up of patients admitted for hiccup in Hospital Clinico de
      Santiago de Compostela between January 1998 and May 2005. RESULTS: Twenty four
      patients (age 47 to 91 years, 23 males) were studied. Nineteen (79%) were
      admitted because of persistent hiccups. In twenty one patients, at inverted
      exclamation markeast one organic etiology was identified, and thirteen patients
      presented two or more possible associated conditions. The most common possible
      causes were digestive tract disorders, followed by central nervous system
      diseases. Twelve patients had a history of exposure to drugs that potentially
      could cause hiccups, mainly corticosteroids and benzodiazepines. Chlorpromazine
      was the first choice treatment in 23 patients, but seven required a second line
      drug. Average hospital stay was 13 days (range 3-90 days). Twelve patients died
      during follow up. Death occurred during the first three months of follow up in
      61%. CONCLUSIONS: Persistent hiccup is often associated with organic conditions,
      specially advanced tumors of the digestive tract. It is usually associated with a
      bad prognosis.

PMID- 18064368
TI  - [Immunohistochemistry of degenerative changes in the central nervous system in
      spastic paraparesis associated to human T lymphotropic virus type I (HTLV-I)].
AB  - BACKGROUND: Human T lymphotropic virus type I is associated with tropical spastic
      paraparesis, that is a chronic and progressive disease which damages specially
      the cortiespinal tracts. The pathogenesis of this degenerative process remains
      unknown. AIM: To identify histopathological aspects that could suggest a
      pathogenic hypothesis we studied immunohistochemical features in spinal cords
      obtained from patients that died due to progressive spastic paraparesis. PATIENTS
      AND METHODS: Five males and five females, who died between 1990 and 2000, with a
      mean age of 52 years and mean disease duration of 8.6, were studied. All had a
      complete clinical and virological diagnosis. Samples were obtained from the
      frontal motor cortex and spinal cord (cervical, dorsal and lumbar segments), were
      fixed in formol (10%), included in paraffin, and stained with Haematoxylin and
      Luxol-fast-blue. Immunohistochemical study was made with anti-neurofilament
      antibodies 1:100 (M0762, DAKO), anti-APP 1:20 (Rabbit Pre Amyloid protein 51-2700
      ZYMED), anti-tau 1:100 (A0024 DAKO) and anti-ubiquitine 1:50 (NCL UBIQm
      Novocastra). RESULTS: All cases had demyelinization and axonal loss in the
      cortico-spinal tracts; distal and segmental demyelinization of Goll tract; axonal
      thickening, amyloid precursor protein deposits in the white matter; tau protein
      aggregation in the spinal cord oligodendrocytes; axonal ubiquitination of
      sensitive and motor tracts, and subcortical white matter. Neurona! injury was
      absent. CONCLUSIONS: The systematic damage of motor and sensitive tracts of the
      spinal-cord and the absence of neurona! damage, defines a degenerative process
      limited to axons. This central axonopathie could be caused by a disturbance of
      axoplasmic transport.

PMID- 18064369
TI  - [Clinical and ultrastructural features of ciliary dyskinesia].
AB  - BACKGROUND: Ciliary dyskinesia (CD) is a low incidence genetic illness, that
      presents with a wide clinical spectrum. Also, there are transitory conditions
      that present with ciliary anomalies, secondary to infectious diseases of the
      airways. AIM: To descube clinical and ultrastructural findings and clinical and
      therapeutic evolution of these patients. PATIENTS AND METHODS: Retrospective
      review of medical records and electron microscopy findings of 33 patients (aged 1
      to 21 years, 14 females) with ultrastructural diagnosis of CD. To obtain follow
      up information, a telephone survey was done. RESULTS: In 30 patients (90%) the
      inner dynein arm (IDA) was absent in 50 or more percent of the cilia. Twenty two
      (66%) had absence of the outer dynein arm. Before diagnosis of CD, 19 patients
      (57%) presented recurrent otitis media, 25 patients (77%), three or more episodes
      of rhinosinusitis and 18 patients (56%) had recurrent pneumonia. Middle ear
      ventilation tubes were placed in 19 patients (57%), and during its use, 12 (68%)
      remained without othorrea. Sixteen patients (48%) with recurrent episodes of
      rhinosinusitis required adenoidectomy Seven (21%) required a functional
      endoscopic sinus surgery (FESS), and 6 (86%) improved after FESS. CONCLUSIONS:
      Our patients with CD presented recurrent infections in different airway
      locations. In those with a diagnosis of CD and recurrent otologica! and
      rhinosinusal infections, IDA was absent in a high percentage of cilia. FESS and
      the use of ventilation tubes may have a beneficial role in a subgroup of patients
      with CD.

PMID- 18064370
TI  - [The notion of decision making capacity in medical and legal practice].
AB  - BACKGROUND: The relationship between patients and health professionals emphasizes
      deliberation and joint decision making, that derives in the informed consent.
      AIM: To evaluate decision making of patients in health care and to identify the
      notion of capacity for decision making, according to lawyers and physicians.
      MATERIAL AND METHODS: A semi-structured interview about procedures to assess
      decision making capacity was applied to 27 selected physicians and lawyers,
      considering their experience in this area. A qualitative analysis of answers was
      performed. RESULTS: Several differences were observed between physicians and
      lawyers, probably originated in their respective disciplines as well as the
      context of their professional practice. For physicians the notion of capacity is
      associated to comprehension of the information, it is not absolute, and it must
      consider the intellectual maturity of the teenager and the autonomy of the
      elderly. This evaluation is frequently performed in the clinical interview and
      standardized protocols do not exist. For lawyers, capacity is established by age
      and is associated to rights and obligations, as determined by law. When it is
      assessed by experts, including physicians, it becomes evidence. These
      professionals assume that experts will use standardized assessment instruments.
      Capacity has significance in the legal system. CONCLUSIONS: Since there are
      substantial consequences when a person is deemed incompetent, it is necessary to
      distinguish between health capacity and legal capacity, and to inverted
      exclamation markink the informed consent with the fundamental rights of citizens,
      such as taking decisions about our own health.

PMID- 18064371
TI  - [Prevalence and epidemiology of Loxosceles laeta bite. Analysis of consultations
      to a poison control center].
AB  - BACKGROUND: Loxoscelism is caused by the bite of spider Loxosceles laeta. It can
      cause a cutaneous or systemic syndrome. AIM: To determine the epidemiologica! and
      clinical features of patients bitten by the Chilean recluse spider (Loxosceles
      laeta). MATERIAL AND METHODS: All communications received at a telephonic
      orientation center for intoxications during 2005 were analyzed, selecting those
      who involved patients with symptoms that suggested loxoscelism (i.e., pain,
      burning sensation, blue area, hematuria, fever or myalgia). These were derived to
      the emergency room for confirmation of the diagnosis. Forty-eight hours after the
      initial communication, patients were contacted by phone to find out about the
      definitive diagnosis. The variables analyzed were: gender, age, geographical
      location, time since exposure, part of the body involved, clinical signs and
      definitive diagnosis. RESULTS: Of 2,831 telephonic consultations with suspected
      loxoscelism, the diagnosis was confirmed in 287. All of these patients had
      cutaneous loxoscelism and only 7.3% of them developed visceral loxoscelism. Fifty
      six percent of patients with loxoscelism presented two or more clinical signs.
      The most common were a blue area, pain and a burning sensation, in 69%, 58% and
      38% of patients, respectively. Fifty-one percent of patients developed signs
      within the first 12 hours. All patients with visceral syndrome presented with
      hemoglobinuria. No cases of loxoscelism were registered in areas located southern
      than the Xth region of Chile. There were no fatalities attributed to loxoscelism.
      CONCLUSIONS: Most cases of loxoscelism of this series were cutaneous. The
      population must be educated about the clinical signs of spider bite to seek early
      and adequate medical treatment.

PMID- 18064372
TI  - [Lymph node involvement in classic Kaposi sarcoma: report of three cases].
AB  - Classic Kaposi s sarcoma (KS) affects lower extremities in older adults, showing
      a progressive, benign course. It can also involve oral mucosa and
      gastrointestinal tract with a lower frequency. The involvement of internal organs
      and lymph nodes is rare, and its primary compromise is even more uncommon. We
      report an unusual presentation of classic KS in the lymph nodes of three
      patients. A 46 years old male had a primary involvement of an inguinal lymph
      node. Dermal involvement appeared one year later. A 58years old male and a
      76years old female with simultaneous dermal and lymph node involvement. We
      conclude that the presence of classic KS in our region is more common than
      previously considered. Moreover, it must be emphasized that KS in lymph nodes can
      affect HIV-negative patients or patients without any associated immune
      deficiency.

PMID- 18064373
TI  - [Pulmonary resection of lung metastases of a uterine leiomyosarcoma: report of a
      case].
AB  - We report a 45 years-old woman operated in 2003 for a stage IV uterine
      leiomyosarcoma with lung metastases. Pulmonary metastases were surgically excised
      in 2003, 2005 and finally in July, 2006. Since then, the patient is in good
      conditions. There is evidence that resection of pulmonary metastases of
      gynecologic cancers, when the primary tumor is controlled, significantly prolongs
      survival.

PMID- 18064374
TI  - [Primary angiosarcoma of the spleen: report of one case].
AB  - Primary angiosarcoma of the spleen is rare and almost always fatal. The
      pathogenesis is unknown. It has an aggressive behavior and frequently presents
      with hematological abnormalities or metastatic disease. We report a 49 year-old
      male that presented with spleen and lymph node enlargement. He was subjected to a
      splenectomy and the biopsy disclosed an angiosarcoma of the spleen. Metastases
      were detected in the lung and bones and the patient was considered beyond any
      therapeutic option, dying fifteen months later.

PMID- 18064375
TI  - [Severe aneurismal coronary artery disease probably caused by Kawasaki disease.
      report of one case].
AB  - We report a 16 year old male with a history of angina on exertion. A treadmill
      exercise test was positive for ischemia in concordance with a Thallium-201
      scintigraphy showing a septal and infero-posterior reversible myocardial
      perfusion defect. Coronary angiography disclosed severe aneurysmal coronary
      artery disease. Bilateral internal mammary coronary artery bypass grafting was
      successfully performed. Kawasaki disease is the most likely etiology, although
      not confirmed.

PMID- 18064376
TI  - [Adult celiac disease].
AB  - Celiac disease is a chronic enteropathy caused by intolerance to gluten. The true
      prevalence of this condition is much greater than previously recognized, with
      more silent cases being diagnosed and a greater proportion of cases diagnosed
      later in adulthood. It presents with a spectrum of clinical manifestations and
      histological abnormalities. Duodenal biopsy remains the gold standard for
      diagnosis of celiac disease, even though there are new serologic tests that are
      very specific. Correlation of clinical, serologic, and histological features are
      essential for a definitive diagnosis of celiac disease. The pathogenesis consists
      in an interaction between genetic, immunologic and environmental factors, which
      interact with HLA molecules to activate an immunologic response in the small
      bowel mucosa causing tissue damage. The main treatment is a free gluten diet.
      Health risks for untreated celiac disease appear to be greater compared with
      those patients who adhere to this treatment.

PMID- 18064377
TI  - [Do antidepressants really increase suicide rates in childhood and adolescence?].
AB  - The use of antidepressant in depressive illness results in a reduction of
      suicidal attempts and deaths due to suicide, conditions that are generally
      present in this disorder. Recently, the Federal Drug Administration (FDA)
      prohibited the use of antidepressants during childhood and adolescence. This
      decision was based on a supposed increase in suicidal thinking in these age
      groups. However, the evidence came from flawed clinical studies, some of them not
      even published, in which no significant differences were observed when compared
      to placebo. It is not possible to ascribe a direct responsibility to
      antidepressants, because depression, by definition, has suicidal ideation. On the
      contrary, the reduction of suicidal rates supports the effectiveness of these
      medications.

PMID- 18064378
TI  - [Analysis of a university training program in endocrinology].
AB  - The Pontificia Universidad Catolica de Chile has a two decades experience in
      training endocrinology specialists. This communication explains the operation of
      the training program and the results of a survey, answered by 90% of
      Endocrinologists that were trained at the center. This survey covers different
      aspects of the program such as the strengths and weaknesses of the academic
      teaching and the present position of the trainees. Questions about the working
      environment and the relationship with their teachers during the application of
      the program are also included. These results can be useful for other University
      centers that are planning a training program in endocrinology and for those
      physicians that are planning to become endocrinologists.

PMID- 18064379
TI  - [The profile and number of primary care physicians required in Chile].
AB  - Medical schools curricular planning aim to obtain a physician trained to work as
      general practitioner and the Chilean health reform, considers ambulatory primary
      care as the main axis of health care. However there is still a low interest among
      physicians to work in primary health care, where there are problems related to a
      low level of clinical resolution, clinical and administrative management
      deficiencies and a low level of leadership in health promotion. The causes of
      these deficiencies stem from university training, government policies and the
      great attraction that exerts the technological and specialized model of secondary
      and tertiary health care. We analyze the ideal profue that the general
      practitioner should have in our health care system and the possible solutions to
      primary health care problems. We also emphasize the need to coordinate the
      professional resource needs with university training, to reduce the existing gaps
      between medical training and professional practice.

PMID- 18064380
TI  - [The medical history of Edgar Allan Poe].
AB  - Edgar Allan Poe, one of the best American storytellers and poets, suffered an
      episodic behaviour disorder partially triggered by alcohol and opiate use. Much
      confusion still exists about the last days of his turbulent life and the cause of
      his death at an early age. Different etiologies have been proposed to explain his
      main medical problem, however, complex partial seizures triggered by alcohol,
      poorly recognized at the time when Poe lived, seems to be one of the most
      acceptable hypothesis, among others discussed.

PMID- 18064381
TI  - [Stem-cell therapy].

PMID- 18064382
TI  - [A class on religious tolerance].

PMID- 18064383
TI  - Roles of F-box proteins in plant hormone responses.
AB  - The F-box protein is an important component of the E3 ubiquitin ligase Skp1
      Cullin-F-box protein complex. It binds specific substrates for ubiquitin-mediated
      proteolysis. The F-box proteins contain a signature F-box motif at their amino
      terminus and some protein-protein interaction motifs at their carboxy-terminus,
      such as Trp-Asp repeats or leucine rich repeats. Many F-box proteins have been
      identified to be involved in plant hormone response as receptors or important
      medial components. These breakthrough findings shed light on our current
      understanding of the structure and function of the various F-box.

PMID- 18064384
TI  - Contribution of CDP/Cux, a transcription factor, to cell cycle progression.
AB  - CCAAT-displacement protein/Cut homeobox (CDP/Cux) was initially identified as a
      transcriptional repressor. However, a number of studies have now suggested that
      CDP/Cux is a transcriptional activator as well. Stable DNA binding activity of
      CDP/Cux is up-regulated at the G(1)/S transition by two mechanisms,
      dephosphorylation by the Cdc25A phosphatase and proteolytic processing to
      generate a 110 kDa amino-truncated isoform, CDP/Cux p110. The generation of
      CDP/Cux p110 stimulates the expression of reporter plasmid containing the
      promoter sequences of some S phase-specific-genes such as DNA polymerase a gene,
      dihydrofolate reductase gene, carbamoyl-phosphate synthase/aspartate carbamoyl
      transferase/dihydroorotase gene, and cyclin A gene. However, DNA binding activity
      of CDP/Cux is down-regulated at G(2) phase through a binding of cyclin A-cyclin
      dependent kinases1 (Cdk1) to CDP/Cux. Furthermore, another CDP/Cux isoform,
      CDP/Cux p75, has been found to be associated with breast tumors indicating this
      isoform is involved in the abnormal proliferation of tumor cells. The differences
      in DNA binding of CDP/Cux isoforms in S and G(2) phases suggest important roles
      of CDP/Cux in cell cycle progression. In this review, we discuss the functions of
      CDP/Cux with a focus on its roles in cell cycle regulation and its possible
      potency leading to the cell cycle reentry of neurons.

PMID- 18064385
TI  - Reversible histone acetylation involved in transcriptional regulation of WT1
      gene.
AB  - To validate the involvement of reversible histone acetylation in the
      transcriptional regulation of human Wilms' tumor 1 gene (WT1), we analyzed the
      roles of histone deacetylases (HDACs) and histone acetyltransferase in this
      epigenetic process. Of the six HDACs (HDAC1-6) examined, HDAC4 and HDAC5 were
      found to have significant repressing effects on the activity of the WT1 reporter
      gene, as revealed by luciferase reporter assays and quantitative real-time
      reverse transcription-polymerase chain reaction assays. Luciferase reporter
      assays showed that the histone acetyltransferase p300 was able to counteract the
      HDAC4/HDAC5-mediated repression and that p300/CBP synergized with transcription
      factors Sp1, c-Myb, and Ets-1 in activation of the WT1 reporter. Chromatin
      immunoprecipitation experiments showed that p300 promotes the acetylation level
      of histone H3 at the WT1 intronic enhancer. Based on these data, we proposed a
      hypothetical model for the involvement of reversible histone acetylation in
      transcriptional regulation of the WT1 gene. This study provides further insight
      into the mechanisms of transcriptional regulation of the WT1 gene and WT1
      associated diseases treatment.

PMID- 18064386
TI  - Identification of the gene imds-60 in mouse epididymis.
AB  - Sperm maturation, including the acquisition of motility and the full ability to
      fertilize oocyte, occurs during its transit through the dynamic environment of
      the epididymis. However, the roles of many genes involved in the process of sperm
      maturation still remain to be found. Based on an expressed sequence tag named
      imds-60, which was first found in uterus but is highly expressed in epididymis,
      the full-length cDNA sequence of imds-60 with a complete open reading frame was
      obtained in mouse epididymis by GenBank searching, polymerase chain reaction
      based procedures, and 5'- and 3'-rapid amplification of cDNA ends. This protein
      was predicted to have an N-terminal signal peptide and a C-terminal DNase I-like
      domain with nine transmembrane motifs in the middle part of the protein. Northern
      blot analysis showed that the mRNA of imds-60 was highly expressed in epididymis
      but at a rather lower level in uterus, seminal vesicle gland, and stomach.
      Further study revealed that the mRNA of imds-60 is only expressed in corpus and
      cauda regions of epididymis, not in caput. It is regulated partially by androgen
      and peaked in male mice aged from 3 weeks to adult. The imds-60 protein might
      play an important role in cell communication during sperm maturation.

PMID- 18064387
TI  - Purification and characterization of glyceraldehyde-3-phosphate dehydrogenase
      from European pilchard Sardina pilchardus.
AB  - The NAD+-dependent cytosolic glyceralehyde-3-phosphate dehydrogenase (GAPDH; EC
      1.2.1.12) was purified from the skeletal muscle of European pilchard Sardina
      pilchardus and its physicochemical and kinetic properties were investigated. The
      purification method consisted of two steps, ammonium sulfate fractionation
      followed by Blue Sepharose CL-6B chromatography, resulting in an approximately 78
      fold increase in specific activity and a final yield of approximately 25%. The
      Michaelis constants (K(m)) for NAD+ and D-glyceraldehyde-3-phosphate were 92.0
      microM and 73.4 microM, respectively. The maximal velocity (V(max)) of the
      purified enzyme was estimated to be 37.6 U/mg. Under the assay conditions, the
      optimum pH and temperature were 8.0 and 30 degrees C. The molecular weight of the
      purified enzyme was 37 kDa determined by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. Non-denaturing polyacrylamide gels yielding a molecular
      weight of 154 kDa suggested that the enzyme is a homotetramer. Polyclonal
      antibodies against the purified enzyme were used to recognize the enzyme in
      different sardine tissues by Western blot analysis. The isoelectric point,
      obtained by an isoelectric focusing system in polyacrylamide slab gels, revealed
      only one GAPDH isoform (pI 7.9).

PMID- 18064388
TI  - Cloning and characterization of a heterogeneous nuclear ribonucleoprotein homolog
      from pearl oyster, Pinctada fucata.
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) have fundamental roles in the
      post-transcriptional control of gene expression. Here, a cDNA encoding a presumed
      full-length RNA-binding protein was isolated from pearl oyster (Pinctada fucata)
      using reverse transcription-polymerase chain reaction with degenerate primers,
      and rapid amplification of cDNA ends. The full-length cDNA consists of 2737 bp
      with an open reading frame encoding a protein of 624 amino acids with a predicted
      molecular weight of 69 kDa and isoelectric point of 8.7. The putative pearl
      oyster RNA-binding protein presents a molecular organization close to the hnRNPs,
      namely an acidic N-terminal followed by three RNA-recognition motifs and a C
      terminal that contains RG/RGG repeated motifs. When transfected HeLa cells, the
      Pf-HRPH (Pinctada fucata hnRNP homolog) gene expression product was found only in
      nuclei, revealing that it is a nuclear protein. The expression pattern was also
      investigated by quantitative real-time polymerase chain reaction, indicating that
      Pf-HRPH mRNA was abundantly expressed in gonad, gill, and viscera. As far as we
      know, the putative Pf-HRPH is the first hnRNP homolog cloned in mollusks. These
      data are significant for further study of the multiple functions of RNA-binding
      protein.

PMID- 18064389
TI  - Abnormally high expression of BAFF on T lymphocytes from lung cancer-associated
      pleural effusions and its potent anti-tumor effect.
AB  - In the present study, the expressions of B cell activating factor belonging to
      the tumor necrosis factor family (BAFF) and its receptors (BAFF-R and TACI) on T
      lymphocytes from malignant pleural effusion (MPE) were examined by fluorescence
      activated cell sorting (FACS) analysis, and compared with those on the T
      lymphocytes from non-malignant pleural effusion (NMPE) and healthy controls. It
      was found that CD3 positive T lymphocytes (including CD4, CD8, and part of CD25
      and CD69 positive cells) of MPE in lung cancer highly and consistently expressed
      the BAFF molecule, while high expressions of BAFF could only be found in
      phytohemagglutinin (PHA) or interleukin 2 (IL-2) induced T lymphocytes from NMPE
      or healthy controls. These results were consistent with the results from BAFF
      mRNA detection by real-time PCR. In addition, T lymphocytes from MPE expressed
      significantly more BAFF-R than those from NMPE or healthy controls, while the
      expression of TACI was increased on CD4+ T cells but decreased on CD8+ T cells
      when compared with controls. The Annexin/PI assay suggested that recombinant
      human BAFF (rhBAFF) could promote the survival rate of T lymphocytes from MPE,
      while the decoy receptor TACI-Fc fusion protein could promote the apoptosis rate
      of T lymphocytes. Cytokines in the supernatant detected by ELISA assay showed
      that rhBAFF could significantly upregulate the secretion of IFN-gamma in vitro,
      and the IFN-gamma level in the TACI-Fc-treated group resembled that of the
      control groups. All of these results indicated that the abnormally high
      expression of BAFF on T lymphocytes from MPE may play a role of anti-tumor
      effect.

PMID- 18064390
TI  - Effect of exogenous ghrelin on cell differentiation antigen 40 expression in
      endothelial cells.
AB  - Ghrelin is a brain-gut peptide that serves as a natural ligand for growth hormone
      secretagogue receptor (GHSR). It also exists abundantly in the cardiovascular
      system. In order to evaluate the possible role of ghrelin in the development of
      atherosclerosis, the effect of ghrelin on the expression of cell differentiation
      antigen 40 (CD40) were studied. Human umbilical vein endothelial cell (HUVEC)
      line-ECV 304 was pre-treated with different concentrations of ghrelin, des-acyl
      ghrelin or [d-Lys]-GHRP-6 (a ghrelin receptor antagonist), and then induced with
      tumor necrosis factor-alpha (TNF-alpha) and interferon gamma (IFN-gamma). The
      mRNA levels of CD40 were analyzed by reverse transcription-polymerase chain
      reaction, and the expressions of CD40 protein in the cells were measured by flow
      cytometry (FCM) and Western blotting. The results showed that exogenous ghrelin
      could significantly inhibit TNF-alpha/IFN-gamma induced CD40 expression in HUVEC
      cells in a concentration-dependent manner. When treated with 1000 ng/ml of
      ghrelin, the mRNA level of CD40 in the cells was decreased by approximately 77%,
      but when treated with both 1000 ng/ml of ghrelin and 1000 ng/ml of [d-Lys]-GHRP
      6, the mRNA level of CD40 in the cells was decreased by only 42%, suggesting that
      [d-Lys]-GHRP-6 could counteract the inhibitory effect of ghrelin in these cells.
      However, CD40 expression was not inhibited by des-acyl ghrelin at 1000 ng/ml. The
      results in protein expression analysis detected by FCM and Western blotting
      further confirmed these results. Our results suggested that in the cardiovascular
      system, ghrelin not only has an anti-inflammatory effect, but also has a
      significant immunoregulatory effect that may be mediated through the GHSR-1a
      receptor.

PMID- 18064391
TI  - Gene expression profiling in apoptotic k562 cells treated by homoharringtonine.
AB  - Gene chip technology was used to determine the gene expression profiles in
      apoptotic K562 cells induced by homoharringtonine. The expression of forty-four
      mRNAs was found to be changed significantly were identified after screening with
      a gene chip capable of detecting 14,218 different human mRNA species
      simultaneously. Of these genes, 17 were up-regulated and 27 were down-regulated.
      Most of them were found to be related to apoptosis, oncogenes, or tumor
      suppression. Several genes with altered gene expression, such as human
      transforming growth factor-beta inducible early protein gene (TIEG), vitamin D3
      upregulated protein 1 gene (VDUP1), RNA binding motif protein 4 gene (RBM4) and v
      myc myelocytomatosis viral oncogene homolog (C-MYC), were confirmed by Northern
      blot analysis. According to the dynamic gene expression pattern in these
      apoptotic cells, the activated transforming growth factor-beta and tumor necrosis
      factor signaling pathways play an important role in homoharringtonine-induced
      apoptosis. TIEG was significantly altered after apoptosis induction, it should be
      critical for apoptosis signal transmission.

PMID- 18064392
TI  - Involvement of ghrelin-growth hormone secretagogue receptor system in
      pathoclinical profiles of digestive system cancer.
AB  - Ghrelin receptor has been shown to be expressed along the human gastrointestinal
      tract. Recent studies showed that ghrelin and a synthetic ghrelin receptor
      agonist improved weight gain and lean body mass retention in a rat model of
      cancer cachexia by acting on ghrelin receptor, that is, growth hormone
      secretagogue receptor (GHS-R). This study aims to explore the expression and the
      distribution of ghrelin receptor in human gastrointestinal tract cancers and to
      investigate the possible involvement of the ghrelin-GHS-R system in human
      digestive cancers. Surgical human digestive cancer specimens were obtained from
      various portions of the gastrointestinal tract from different patients. The
      expression of ghrelin receptor in these tissues was detected by tissue microarray
      technique. Our results showed that ghrelin receptor was expressed in cancers
      throughout the gastrointestinal tract, mainly in the cytoplasm of mucosal layer
      cells. Its expression level possibly correlated with organ type, histological
      grade, tumor-nodes-metastases stage, and nutrition status (weight loss) of the
      patients. For the first time, we identified the distribution of ghrelin receptor
      in digestive system cancers. Our results implied that the ghrelin-GHS-R system
      might be involved in the pathoclinical profiles of digestive cancers.

PMID- 18064393
TI  - Knockdown of S-phase kinase-associated protein-2 expression in MCF-7 inhibits
      cell growth and enhances the cytotoxic effects of epirubicin.
AB  - S-phase kinase-associated protein-2 (Skp2) plays a key role in ubiquitin-mediated
      proteolysis, resulting in the progression of cells from a quiescent to a
      proliferative state. Skp2 is overexpressed in a variety of tumors and inversely
      correlated with p27 expression, including breast cancer. In this study, we used
      small interfering RNAs (siRNAs) to inhibit Skp2 expression in human breast cancer
      MCF-7 cells and thereby investigate if knockdown of Skp2 by RNA interference
      (RNAi) would inhibit breast cancer cell growth and influence the effects of
      epirubicin on MCF-7 cells. Three Skp2 siRNA constructs were recombined and
      transiently transfected human breast cancer MCF-7 cells. Down-regulation of Skp2
      was confirmed by reverse transcription-polymerase chain reaction and Western blot
      analysis. We showed that Skp2 siRNA transfection decreased Skp2 protein and
      induced the accumulation of p27 protein in MCF-7 cells. Skp2 siRNA inhibited the
      cell proliferation both in vitro and in vivo. Knockdown of Skp2 by RNAi increased
      cellular apoptosis in vitro. Treatment with Skp2 siRNA followed by treatment with
      epirubicin further inhibited the proliferation of cancer cell lines, compared
      with control siRNA followed by epirubicin. Therefore, knockdown of Skp2
      expression by RNAi inhibits breast cancer cell growth and enhances the effect of
      epirubicin. siRNA-mediated gene silencing of Skp2 could be a novel cancer gene
      therapy for the suppression of p27 down regulation.

PMID- 18064395
TI  - Is parity in the eye of the beholder?
AB  - To investigate whether parity status can be predicted by physical examination and
      which findings are most predictive. A retrospective chart review of 75
      postmenopausal nulliparous/parous sister pairs who underwent gynecological
      examination as part of a study. An examiner, blinded to parity status, predicted
      parity status based on physical findings recorded on 146 women. Parity status was
      correctly predicted for 84.9% of the women. Of the 22 women for whom parity
      prediction was incorrect, 11 were nulliparous and 11 parous. The physical
      findings most commonly used for prediction were presence or absence of abdominal
      striae, appearance of the cervical os, and condition of hymen. Absence of the
      hymen at 6 o'clock alone correctly predicted parity in 11 of 12 parous and 11 of
      11 nulliparous women. Parity status can be predicted based on physical exam in
      the majority of women. Blinding of investigators to parity status may not be
      feasible.

PMID- 18064394
TI  - A 4-year follow-up study of syndromal and sub-syndromal anxiety and depression
      symptoms in the general population: the HUNT study.
AB  - BACKGROUND: Our aims were to examine the stability of self-rated anxiety and
      depression symptoms and the predictors for change in case-level status after 4
      years in a general population sample. METHODS: Prospective cohort study. Based on
      the total score on the Hospital Anxiety and Depression rating scale (HADS-T) in
      HUNT 2 (1995-1997), three groups were identified: Level 3 (n = 654, score >or= 25
      points), Level 2 (n = 654, score 19-24 points), and Level 1 (n = 1,308, score <
      19 points). The groups were followed up with a mailed questionnaire after 4
      years. RESULTS: Among the 1,326 (53% response rate) who participated in the
      follow-up, 816 (62%) had not changed symptom level. The number of participants
      that had crossed the HADS-T caseness level (19 points) was the same in both
      directions. In non-cases at baseline (Level 1), lack of friends (OR 2.34, 95% CI
      1.28-4.27, P = 0.006) and previous episodes of depression (OR 2.90, 95% CI 1.76
      4.78, P < 0.001) predicted HADS-T caseness at follow-up, while higher educational
      level (OR 0.66, 95% CI 0.46-0.96, P = 0.028) protected from developing caseness
      level of anxiety and depression. In HADS-T cases (Levels 2 and 3) at baseline,
      previous episode(s) of depression (OR 0.36, 95% CI 0.19-0.68, P = 0.002) and
      being unemployed (OR 0.58, 95% CI 0.34-1.00, P = 0.050) predicted HADS-T caseness
      at follow-up, whereas a higher educational level (OR 1.83, 95% CI 1.24-2.70, P =
      0.002) was associated with remission from HADS-T caseness after 4 years.
      CONCLUSIONS: Though symptom fluctuation was considerable, conventional HADS-T
      caseness (>or=19 points) was a reliable and valid predictor for high long-term
      symptom stability of anxiety and depression in our general population sample.

PMID- 18064396
TI  - Comment on Pauls: "Nip, tuck and rejuvenate: the latest frontier for the
      gynecologic surgeon".

PMID- 18064397
TI  - Rare copresent rheumatoid arthritis and gout: comparison with pure rheumatoid
      arthritis and a literature review.
AB  - Copresent rheumatoid arthritis (RA) and gout is seldom reported. This study
      summarizes the findings of eight cases of copresent RA and gout and compares them
      with 31 pure RA cases. Additional reported cases were retrieved from the current
      literature by Medline search. Patients with copresent RA and gout were older (p =
      0.014) and predominantly male (p < 0.01). Synovial fluid, positive for urate
      crystals, was aspirated most frequently from the knee (five out of eight),
      followed by the first metatarsophalangeal joint (three out of eight). Serum
      creatinine and urate levels in the copresent group were significantly higher (p <
      0.01, both), and serum hemoglobin was lower (p = 0.04) than those with pure RA.
      Copresent subjects had much lower percentage of positive rheumatoid factor (RF)
      tests than patients with pure RA (37.5 vs 80.6%). Only one copresent subject had
      both RF and anti-cyclic citrullinated peptide antibody. Of copresent subjects,
      75% had gouty arthritis before diagnosis of RA, which is consistent with earlier
      reports. Seven copresent subjects had gout attacks under disease-modifying
      antirheumatic drug use. This study revealed that polyarthritis negative for RF in
      a previously gouty patient may be RA and vice versa. This combination occurs more
      frequently in males. Moreover, anti-CCP antibody examination is not helpful for
      this diagnosis. Therefore, physicians must obtain synovial fluid for analysis in
      joints with intense swelling, especially in old RA subjects with renal
      insufficiency or involvement of lower extremities. Conversely, RA must be
      considered in gouty patients with polyarticular involvement.

PMID- 18064399
TI  - Laparoscopic ventral hernia repair (LVHR) in morbidly obese patients.
AB  - OBJECTIVE: The aim of this study was to evaluate our experience with LVHR in
      morbidly obese patients (BMI >40) and to compare their outcomes to those of
      patients with lower BMI. METHODS: Data on adult (>18 years old) patients who
      underwent LVHR with mesh over the last 13 years performed by four experienced
      surgeons were collected retrospectively and from a previously collected database.
      Of the 1,071 patients, 901 had completed LVHR and were available for follow-up.
      One hundred and thirty-four patients (group A) met BMI criteria for morbid
      obesity (>or=40, mean 46), 767 patients had BMI < 40, mean 30 (group B). The
      follow-up time ranged from 1 to 91 months. The Wilcoxon rank sum test was used
      for nonparametric data analysis. Outcomes were stratified on the follow up time
      and analyzed using Cochran-Mantel-Haenszel methodology. RESULTS: The groups did
      not differ in terms of ASA score, previous surgery and conversion rate (p=0.22,
      0.32 and 0.23). Morbidly obese patients were younger (48.3 vs. 54; p<0.01) and
      were more often female (p=0.02), but this did not correlate with outcome. Group A
      also had longer operative time (154 vs. 119 min, p<0.01) and hospital stay (3.6
      vs. 2.4 days, p=0.03). Mesh size was significantly larger in group A (449 vs. 349
      cm(2), p=002). During mean follow-up time of 19 months hernia recurrence was 8.3%
      in group A and 2.9% in group B (p=0.003), with an odds ratio of 4.3 (95% CI 1.9
      9.9). However, there was no significant difference in the rate of complications
      (19.7 vs. 15.3%; p=0.46). CONCLUSIONS: LVHR in the morbidly obese population is
      both safe and feasible, although there is a higher, but still acceptable
      recurrence rate. Despite the increased risk for recurrence, LVHR in morbidly
      obese patients minimizes the potential wound and mesh complications that
      frequently occur for open mesh repair in this group of patients.

PMID- 18064398
TI  - The early evolution of the phosphagen kinases--insights from choanoflagellate and
      poriferan arginine kinases.
AB  - Arginine kinase (AK) is a member of a large family of phosphoryl transfer enzymes
      called phosphagen (guanidino) kinases. AKs are present in certain protozoans,
      sponges, cnidarians, and both lophotrochozoan and ecdysozoan protostomes. Another
      phosphagen kinase, creatine kinase (CK), is found in sponges, cnidarians, and
      both deuterostome and protostome groups but does not appear to be present in
      protozoans. To probe the early evolution of phosphagen kinases, we have amplified
      the cDNAs for AKs from three choanoflagellates and from the hexactinellid sponge
      Aphrocallistes beatrix and the demosponges Suberites fuscus and Microciona
      prolifera. Phylogenetic analysis using maximum likelihood of these
      choanoflagellate and sponge AKs with other AK sequences revealed that the AK from
      the choanoflagellate Monosiga brevicollis clusters with the AK from the glass
      sponge Aphrocallistes and is part of a larger cluster containing AKs from the
      demosponges Suberites and Microciona as well as basal and protostome
      invertebrates. In contrast, AKs from Codonosiga gracilis and Monosiga ovata form
      a distinct cluster apart from all other AK sequences. tBLASTn searches of the
      recently released M. brevicollis genome database showed that this species has
      three unique AK genes-one virtually identical to the M. brevicollis cDNA and the
      other two showing great similarity to C. gracilis and M. ovata AKs. Three
      distinct AK genes are likely present in choanoflagellates. Two of these AKs
      display extensive similarity to both CKs and an AK from sponges. Previous work
      has shown CK evolved from an AK-like ancestor prior to the divergence of sponges.
      The present results provide evidence suggesting that the initial gene duplication
      event(s) leading to the CK lineage may have occurred before the divergence of the
      choanoflagellate and animal lineages.

PMID- 18064400
TI  - The complete sequence of ligustrum necrotic ringspot virus, a novel carlavirus.

PMID- 18064401
TI  - Biochemical characterization of DNA-binding proteins from Pyrobaculum aerophilum
      and Aeropyrum pernix.
AB  - Several representatives of the Crenarchaeal branch of the Archaea contain highly
      abundant, small, positively charged proteins exemplified by the Sso7d protein
      from Sulfolobus solfataricus. These proteins bind to DNA in a non-sequence
      specific manner. Using publicly available genomic sequence information, we
      identified a second class of small Crenarchaeal DNA-binding proteins represented
      by the Pyrobaculum aerophilum open reading frame 3192-encoded (Pae3192) protein
      and its paralogs. We investigated the biochemical properties of the Pae3192
      protein and an orthologous protein (Ape1322b) from Aeropyrum pernix in side-by
      side experiments with the Sso7d protein. We demonstrate that the recombinant
      Ape1322b, Pae3192 and Sso7d proteins bind to DNA and that the DNA-protein
      complexes formed are slightly different for each protein. We show that like
      Sso7d, Pae3192 constrains negative supercoils in DNA. In addition, we show that
      all three proteins raise the melting temperature of duplex DNA upon binding.
      Finally, we present the equilibrium affinity constants and kinetic association
      constants of each protein for single-stranded and double-stranded DNA.

PMID- 18064402
TI  - The concept of template-based de novo design from drug-derived molecular
      fragments and its application to TAR RNA.
AB  - Principles of fragment-based molecular design are presented and discussed in the
      context of de novo drug design. The underlying idea is to dissect known drug
      molecules in fragments by straightforward pseudo-retro-synthesis. The resulting
      building blocks are then used for automated assembly of new molecules. A
      particular question has been whether this approach is actually able to perform
      scaffold-hopping. A prospective case study illustrates the usefulness of fragment
      based de novo design for finding new scaffolds. We were able to identify a novel
      ligand disrupting the interaction between the Tat peptide and TAR RNA, which is
      part of the human immunodeficiency virus (HIV-1) mRNA. Using a single template
      structure (acetylpromazine) as reference molecule and a topological pharmacophore
      descriptor (CATS), new chemotypes were automatically generated by our de novo
      design software Flux. Flux features an evolutionary algorithm for fragment-based
      compound assembly and optimization. Pharmacophore superimposition and docking
      into the target RNA suggest perfect matching between the template molecule and
      the designed compound. Chemical synthesis was straightforward, and bioactivity of
      the designed molecule was confirmed in a FRET assay. This study demonstrates the
      practicability of de novo design to generating RNA ligands containing novel
      molecular scaffolds.

PMID- 18064403
TI  - Differential requirement for the function of SRD2, an snRNA transcription
      activator, in various stages of plant development.
AB  - Small nuclear RNA (snRNA) is a class of eukaryotic noncoding RNAs, which have
      essential roles in pre-mRNA splicing and rRNA processing. As these functions are
      fundamental to cell activities, the regulation of snRNA transcription should be a
      vital issue for all eukaryotes. Here we address developmental control of snRNA
      transcription and its significance through the analysis of the SRD2 gene of
      Arabidopsis (Arabidopsis thaliana), which encodes an activator of snRNA
      transcription. In young seedlings, a high level of SRD2 expression was observed
      in shoot and root apical meristems, leaf primordia, and root stele tissues, where
      a large amount of snRNA accumulated. In mature plants, SRD2 was highly expressed
      in developing leaves and flowers as well as apical meristems. Mutations in the
      SRD2 gene interfered with many, but not all, aspects of development in the
      regions that showed strong expression of SRD2. Of note, establishment of the
      fully active state of apical meristems in the seedling stage was very sensitive
      to the srd2-1 mutation, while maintenance of the established meristems was
      substantially insensitive. These results demonstrated differential requirement
      for the SRD2 function in various stages of plant development.

PMID- 18064404
TI  - Arabidopsis RETINOBLASTOMA-RELATED PROTEIN 1 is involved in G1 phase cell cycle
      arrest caused by sucrose starvation.
AB  - Although sucrose availability is crucial for commitment to plant cell division
      during G1 phase by controlling the expression of D-type cyclins, it has remained
      unclear how these factors mediate entry into the cell cycle. Here we show that
      Arabidopsis RETINOBLASTOMA-RELATED PROTEIN 1 (AtRBR1) is involved in G1-phase
      cell cycle arrest caused by sucrose starvation. We generated estrogen-inducible
      AtRBR1 RNA interference (RNAi) Arabidopsis suspension MM2d cells, and found that
      downregulation of AtRBR1 leads to a higher frequency of arrest in G2 phase,
      instead of G1-phase arrest in the uninduced control, after sucrose starvation.
      Synchronization experiments confirmed that downregulation of AtRBR1 leads to a
      prolonged G2 phase and delayed activation of G2/M marker genes. Downregulation of
      AtRBR1 also stimulated the activation of E2F-regulated genes when these genes
      were repressed in the uninduced cells under the limited sucrose conditions. We
      conclude that AtRBR1 is a key effector for the ability of sucrose to modulate
      progression from G1 phase.

PMID- 18064405
TI  - Mineralogy and chemistry of urinary stones: patients from North Jordan.
AB  - Urinary stone diseases are increasing in the Middle East. The majority of urinary
      stone cases are found in the northern part of the country. Stone samples taken
      from patients living in the Irbid area were collected from Princess Basma
      Hospital. The present study concentrates on the mineralogical and chemical
      composition of the urinary stones and on the effective environmental factors that
      assist in developing the different types of urinary stones. Using X-ray
      diffraction techniques, the mineralogical composition of the urinary stones was
      found to be as follows: oxalate, cholesten, and uric acid, with cystine stones
      occuring more frequently than the others. Cholesten and calcium oxalate stones
      are the most dominant types of stones. Calcium oxalate is the most common type of
      oxalate stone. Calcium oxalate is represented in: whewellite, wheddellite, and
      calcium carbonate oxalate hydrate minerals, in addition to other minerals such as
      brushite, ammonium phosphate, vaterite, valleriite, and bobierrite from other
      types of stones. Bobierrite (phosphate group) is a new mineral reported in
      urinary stones, and this has not been determined in any previous study worldwide.
      Apatite (calcium phosphate) is deduced using scanning electron microscope (SEM)
      images. The SEM technique determined crystal forms and systems, shapes,
      morphological features, and the names of the minerals forming urine stones, while
      optical properties are studied by polarizing microscope. X-ray fluorescence
      technique determined the concentrations of major and some trace elements. It
      revealed that Ca is the main constituent of the urinary stones, especially those
      composed of calcium oxalate and calcium phosphate. The concentration of trace
      elements was Ba = 1.57, P = 3.61, Fe = 1.78, S = 2.08, Zr = 4.63, Mo = 3.92, Cu =
      1.89, Co = 1.56, and F = 4.2% and was higher in the urinary stones of Jordanian
      patients than in foreigners in the country. Questionnaires completed by patients
      suggest that the most significant factors directly effecting the formation of
      stones are water, climate conditions, food rich in protein and rich in different
      chemicals. Moreover, some drugs and diseases might also help in developing other
      stones.

PMID- 18064406
TI  - Postmortem cardiac troponin-I levels predict intramyocardial damage at autopsy.
AB  - Serum cardiac troponin levels are now widely used in the diagnosis of myocardial
      infarct (MI) and injury in living patients, but their utility in postmortem
      diagnosis has not been established. We evaluated postmortem cardiac troponin-I
      (cTnI) levels in serum from 53 hospital patients undergoing autopsy and
      correlated the levels with anatomic findings at postmortem examination. Among
      patients with nonischemic cardiac disease, those with intramyocardial disease
      (e.g., cardiac transplant rejection, intramyocardial tumor) had significantly
      higher cTnI levels than those with disease confined to the pericardium (e.g.,
      epicardial tumor implants, pericarditis) (p = 0.004). No correlation was found
      between recent MI and cTnI level. There was also no correlation between cTnI
      level and the presence of chronic ischemic features, a history of cardiopulmonary
      resuscitation, or postmortem interval. We conclude that cTnI is detectable in
      postmortem serum samples and, although its levels did not correlate specifically
      with ischemia or infarction in our series, its levels appear to correlate
      significantly with intramyocardial injury. Use of cardiac troponin in the
      postmortem diagnosis of cardiac disease may be warranted.

PMID- 18064407
TI  - Mutation-prone points in thrombin receptor.
AB  - BACKGROUND: Thrombin receptor (TR) is a G-protein-coupled receptor that transmits
      cellular responses to coagulant proteases in a variety of cell types in the
      vasculature and other tissues. Mutation within TR can be seen. Presently, the
      prediction of protein nanostructure and function is a great challenge in the
      proteomics and structural genomics era. METHODS: To identify the points
      vulnerable to mutation is a new trend directed at expanding the knowledge on
      disorders in genomic and proteomic levels of diseases. In this paper, the author
      performed a bioinformatics analysis to find the mutation-prone positions in the
      amino acid sequence of TR. To identify those points in TR, a new bioinformatics
      tool, namely, GlobPlot was used. RESULTS: According to this work, no position was
      identified to be resistant to mutation. CONCLUSION: This means that TR is a very
      highly genetically unstable molecule. Thousands of types of mutation can be
      expected. Of interest, only a few sense mutations are mentioned in clinical
      settings. Therefore, many occulted sense mutations might still be detected.

PMID- 18064408
TI  - Sinking skin flaps, paradoxical herniation, and external brain tamponade: a
      review of decompressive craniectomy management.
AB  - Decompressive craniectomy is reclaiming a role in neurocritical care. The altered
      pathophysiology found in a cranium converted from a 'closed' box to an 'open'
      box' carries benefits and risks. In some craniectomy patients, the forces of
      atmospheric pressure and gravity overwhelm intracranial pressures, and the brain
      appears sunken. This can lead to paradoxical herniation and the sinking skin flap
      syndrome, also called the syndrome of the trephined. At the other polar extreme,
      external brain tamponade occurs when subgaleal fluid accumulates under pressure
      and 'pushes' on the brain across the craniectomy defect. The neuro-intensive care
      team should be prepared to diagnose and treat a spectrum of decompressive
      craniectomy complications including: cerebral contusions, infections, seizures,
      intra- and extra-axial hemorrhages and fluid collections, sinking skin flap
      syndrome or syndrome of the trephined, paradoxical herniation, and external brain
      tamponade. The treating physicians must set aside the Monro-Kellie doctrine and
      recognize the new pathophysiologic state of these 'open box' patients.

PMID- 18064409
TI  - Neurotransmitter release.
AB  - Neurons send out a multitude of chemical signals, called neurotransmitters, to
      communicate between neurons in brain, and between neurons and target cells in the
      periphery. The most important of these communication processes is synaptic
      transmission, which accounts for the ability of the brain to rapidly process
      information, and which is characterized by the fast and localized transfer of a
      signal from a presynaptic neuron to a postsynaptic cell. Other communication
      processes, such as the modulation of the neuronal state in entire brain regions
      by neuromodulators, provide an essential component of this information processing
      capacity. A large number of diverse neurotransmitters are used by neurons,
      ranging from classical fast transmitters such as glycine and glutamate over
      neuropeptides to lipophilic compounds and gases such as endocannabinoids and
      nitric oxide. Most of these transmitters are released by exocytosis, the i.e. the
      fusion of secretory vesicles with the plasma membrane, which exhibits distinct
      properties for different types of neurotransmitters. The present chapter will
      provide an overview of the process of neurotransmitter release and its historical
      context, and give a reference point for the other chapters in this book.

PMID- 18064410
TI  - Pharmacology of neurotransmitter release: measuring exocytosis.
AB  - Neurotransmission in the nervous system is initiated at presynaptic terminals by
      fusion of synaptic vesicles with the plasma membrane and subsequent exocytic
      release of chemical transmitters. Currently, there are multiple methods to detect
      neurotransmitter release from nerve terminals, each with their own particular
      advantages and disadvantages. For instance, most commonly employed methods
      monitor actions of released chemical substances on postsynaptic receptors or
      artificial substrates such as carbon fibers. These methods are closest to the
      physiological setting because they have a rapid time resolution and they measure
      the action of the endogenous neurotransmitters rather than the signals emitted by
      exogenous probes. However, postsynaptic receptors only indirectly report
      neurotransmitter release in a form modified by the properties of receptors
      themselves, which are often nonlinear detectors of released substances.
      Alternatively, released chemical substances can be detected biochemically, albeit
      on a time scale slower than electrophysiological methods. In addition, in certain
      preparations, where presynaptic terminals are accessible to whole cell recording
      electrodes, fusion of vesicles with the plasma membrane can be monitored using
      capacitance measurements. In the last decade, in addition to electrophysiological
      and biochemical methods, several fluorescence imaging modalities have been
      introduced which report synaptic vesicle fusion, endocytosis, and recycling.
      These methods either take advantage of styryl dyes that can be loaded into
      recycling vesicles or exogenous expression of synaptic vesicle proteins tagged
      with a pH-sensitive GFP variant at regions facing the vesicle lumen. In this
      chapter, we will provide an overview of these methods with particular emphasis on
      their relative strengths and weaknesses and discuss the types of information one
      can obtain from them.

PMID- 18064411
TI  - Presynaptic calcium channels: structure, regulators, and blockers.
AB  - The central and peripheral nervous systems express multiple types of ligand and
      voltage-gated calcium channels (VGCCs), each with specific physiological roles
      and pharmacological and electrophysiological properties. The members of the
      Ca(v)2 calcium channel family are located predominantly at presynaptic nerve
      terminals, where they are responsible for controlling evoked neurotransmitter
      release. The activity of these channels is subject to modulation by a number of
      different means, including alternate splicing, ancillary subunit associations,
      peptide and small organic blockers, G-protein-coupled receptors (GPCRs), protein
      kinases, synaptic proteins, and calcium-binding proteins. These multiple and
      complex modes of calcium channel regulation allow neurons to maintain the
      specific, physiological window of cytoplasmic calcium concentrations which is
      required for optimal neurotransmission and proper synaptic function. Moreover,
      these varying means of channel regulation provide insight into potential
      therapeutic targets for the treatment of pathological conditions that arise from
      disturbances in calcium channel signaling. Indeed, considerable efforts are
      presently underway to identify and develop specific presynaptic calcium channel
      blockers that can be used as analgesics.

PMID- 18064412
TI  - Pharmacology of neurotransmitter transport into secretory vesicles.
AB  - Many neuropsychiatric disorders appear to involve a disturbance of chemical
      neurotransmission, and the mechanism of available therapeutic agents supports
      this impression. Postsynaptic receptors have received considerable attention as
      drug targets, but some of the most successful agents influence presynaptic
      processes, in particular neurotransmitter reuptake. The pharmacological potential
      of many other presynaptic elements, and in particular the machinery responsible
      for loading transmitter into vesicles, has received only limited attention. The
      similarity of vesicular transporters to bacterial drug resistance proteins and
      the increasing evidence for regulation of vesicle filling and recycling suggest
      that the pharmacological potential of vesicular transporters has been
      underestimated. In this review, we discuss the pharmacological effects of
      psychostimulants and therapeutic agents on transmitter release.

PMID- 18064413
TI  - Core proteins of the secretory machinery.
AB  - Members of the Rab, SM- and SNARE-protein families play key roles in all
      intracellular membrane trafficking steps. While SM- and SNARE-proteins become
      directly involved in the fusion reaction at a late stage, Rabs and their
      effectors mediate upstream steps such as vesicle budding, delivery, tethering,
      and transport. Exocytosis of synaptic vesicles and regulated secretory granules
      are among the best-studied fusion events and involve the Rab3 isoforms Rab3A-D,
      the SM protein munc18-1, and the SNAREs syntaxin 1A, SNAP-25, and synaptobrevin
      2. According to the current view, syntaxin 1A and SNAP-25 at the presynaptic
      membrane form a complex with synaptic vesicle-associated synaptobrevin 2. As
      complex formation proceeds, the opposed membranes are pulled tightly together,
      enforcing the fusion reaction. Munc18-1 is essential for regulated exocytosis and
      interacts with syntaxin 1A alone or with SNARE complexes, suggesting a role for
      munc18-1 in controlling the SNARE-assembly reaction. Compared to other
      intracellular fusion steps, special adaptations evolved in the synapse to allow
      for the tight regulation and high membrane turnover rates required for synaptic
      transmission. Synaptic vesicle fusion is triggered by the intracellular second
      messenger calcium, with members of the synaptotagmin protein family being prime
      candidates for linking calcium influx to fusion in the fast phase of exocytosis.
      To compensate for the massive incorporation of synaptic vesicles into the plasma
      membrane during exocytosis, special adaptations to endocytic mechanisms have
      evolved at the synapse to allow for efficient vesicle recycling.

PMID- 18064414
TI  - Presynaptic neurotoxins with enzymatic activities.
AB  - Toxins that alter neurotransmitter release from nerve terminals are of
      considerable scientific and clinical importance. Many advances were recently made
      in the understanding of their molecular mechanisms of action and use in human
      therapy. Here, we focus on presynaptic neurotoxins, which are very potent
      inhibitors of the neurotransmitter release because they are endowed with specific
      enzymatic activities: (1) clostridial neurotoxins with a metallo-proteolytic
      activity and (2) snake presynaptic neurotoxins with a phospholipase A2 activity.

PMID- 18064416
TI  - Presynaptic signaling by heterotrimeric G-proteins.
AB  - G-proteins (guanine nucleotide-binding proteins) are membrane-attached proteins
      composed of three subunits, alpha, beta, and gamma. They transduce signals from G
      protein coupled receptors (GPCRs) to target effector proteins. The
      agonistactivated receptor induces a conformational change in the G-protein trimer
      so that the alpha-subunit binds GTP in exchange for GDP and alpha-GTP, and
      betagamma-subunits separate to interact with the target effector. Effector
      interaction is terminated by the alpha-subunit GTPase activity, whereby bound GTP
      is hydrolyzed to GDP. This is accelerated in situ by RGS proteins, acting as
      GTPase-activating proteins (GAPs). Galpha-GDP and Gbetagamma then reassociate to
      form the Galphabetagamma trimer. G-proteins primarily involved in the modulation
      of neurotransmitter release are G(o), G(q) and G(s). G(o) mediates the widespread
      presynaptic auto-inhibitory effect of many neurotransmitters (e.g., via M2/M4
      muscarinic receptors, alpha(2) adrenoreceptors, micro/delta opioid receptors,
      GABAB receptors). The G(o) betagamma-subunit acts in two ways: first, and most
      ubiquitously, by direct binding to CaV2 Ca(2+) channels, resulting in a reduced
      sensitivity to membrane depolarization and reduced Ca(2+) influx during the
      terminal action potential; and second, through a direct inhibitory effect on the
      transmitter release machinery, by binding to proteins of the SNARE complex. G(s)
      and G(q) are mainly responsible for receptor-mediated facilitatory effects,
      through activation of target enzymes (adenylate cyclase, AC and phospholipase-C,
      PLC respectively) by the GTP-bound alpha-subunits.

PMID- 18064417
TI  - Presynaptic metabotropic receptors for acetylcholine and
      adrenaline/noradrenaline.
AB  - Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline
      were first described more than three decades ago. Molecular cloning has resulted
      in the identification of five G protein-coupled muscarinic receptors (M(1) -
      M(5)) which mediate the biological effects of acetylcholine. Nine adrenoceptors
      (alpha(1ABD),alpha(2ABC),beta(123)) transmit adrenaline/noradrenaline signals
      between cells. The lack of sufficiently subtype-selective ligands has prevented
      identification of the physiological role and therapeutic potential of these
      receptor subtypes for a long time. Recently, mouse lines with targeted deletions
      for all muscarinic and adrenoceptor genes have been generated. This review
      summarizes the results from these gene-targeting studies with particular emphasis
      on presynaptic auto- and heteroreceptor functions of muscarinic and adrenergic
      receptors. Specific knowledge about the function of receptor subtypes will
      enhance our understanding of the physiological role of the cholinergic and
      adrenergic nervous system and open new avenues for subtype-selective therapeutic
      strategies.

PMID- 18064418
TI  - Presynaptic receptors for dopamine, histamine, and serotonin.
AB  - Presynaptic receptors for dopamine, histamine and serotonin that are located on
      dopaminergic, histaminergic and sertonergic axon terminals, respectively,
      function as autoreceptors. Presynaptic receptors also occur as heteroreceptors on
      other axon terminals. Auto- and heteroreceptors mainly affect Ca(2+) -dependent
      exocytosis from the receptor-bearing nerve ending. Some additionally subserve
      other presynaptic functions.Presynaptic dopamine, histamine and serotonin
      receptors are involved in various (patho)physiological conditions. Examples are
      the following:Dopamine autoreceptors play a role in Parkinson's disease,
      schizophrenia and drug addiction. Dopamine heteroreceptors affecting the release
      of acetylcholine and of amino acid neurotransmitters in the basal ganglia are
      also relevant for Parkinson's disease. Peripheral dopamine heteroreceptors on
      postganglionic sympathetic terminals influence heart rate and vascular resistance
      through modulation of noradrenaline release. Blockade of histamine autoreceptors
      increases histamine synthesis and release and may support higher CNS functions
      such as arousal, cognition and learning. Peripheral histamine heteroreceptors on
      C fiber and on postganglionic sympathetic fiber terminals diminish neuropeptide
      and noradrenaline release, respectively. Both inhibititory effects are beneficial
      in myocardial ischemia. The inhibition of neuropeptide release also explains the
      antimigraine effects of some agonists of presynaptic histamine receptors.
      Upregulation of presynaptic serotonin autoreceptors is probably involved in the
      pathogenesis of major depression. Correspondingly, antidepressant treatments can
      be linked with a reduced density of 5-HT autoreceptors. 5-HT Heteroreceptor
      activation diminishes acetylcholine and GABA release and may therefore increase
      anxiety. In the periphery, presynaptic 5-HT heteroreceptor agonists shorten
      migraine attacks by inhibition of the release of neuropeptides from trigeminal
      afferents, apart from their constrictive action on meningeal vessels.

PMID- 18064415
TI  - alpha-Latrotoxin and its receptors.
AB  - alpha-Latrotoxin (alpha-LTX) from black widow spider venom induces exhaustive
      release of neurotransmitters from vertebrate nerve terminals and endocrine cells.
      This 130-kDa protein has been employed for many years as a molecular tool to
      study exocytosis. However, its action is complex: in neurons, alpha-LTX induces
      massive secretion both in the presence of extracellular Ca(2+) (Ca(2+) (e)) and
      in its absence; in endocrine cells, it usually requires Ca(2+) (e). To use this
      toxin for further dissection of secretory mechanisms, one needs an in-depth
      understanding of its functions. One such function that explains some alpha-LTX
      effects is its ability to form cation-permeable channels in artificial lipid
      bilayers. The mechanism of alpha-LTX pore formation, revealed by cryo-electron
      microscopy, involves toxin assembly into homotetrameric complexes which harbor a
      central channel and can insert into lipid membranes. However, in biological
      membranes, alpha-LTX cannot exert its actions without binding to specific
      receptors of the plasma membrane. Three proteins with distinct structures have
      been found to bind alpha-LTX: neurexin Ialpha, latrophilin 1, and receptor-like
      protein tyrosine phosphatase sigma. Upon binding a receptor, alpha-LTX forms
      channels permeable to cations and small molecules; the toxin may also activate
      the receptor. To distinguish between the pore- and receptor-mediated effects, and
      to study structure-function relationships in the toxin, alpha-LTX mutants have
      been used.

PMID- 18064419
TI  - Presynaptic adenosine and P2Y receptors.
AB  - Adenine-based purines, such as adenosine and ATP, are ubiquitous molecules that,
      in addition to their roles in metabolism, act as modulators of neurotransmitter
      release through activation of presynaptic P1 purinoceptors or adenosine receptors
      (activated by adenosine) and P2 receptors (activated by nucleotides). Of the
      latter, the P2Y receptors are G protein-coupled, whereas the P2X receptors are
      ligand-gated ion channels and not covered in this review.

PMID- 18064420
TI  - Presynaptic metabotropic glutamate and GABAB receptors.
AB  - Glutamate and GABA, the two most abundant neurotransmitters in the mammalian
      central nervous system, can act on metabotropic receptors that are structurally
      quite dissimilar from those targeted by most other neurotransmitters/modulators.
      Accordingly, metabotropic glutamate receptors (mGluRs) and GABA(B) receptors
      (GABA(B)Rs) are classified as members of family 3 (or family C) of G protein
      coupled receptors. On the other hand, mGluRs and GABA(B)Rs exhibit pronounced and
      partly unresolved differences between each other. The most intriguing difference
      is that mGluRs exist as multiple pharmacologically as well as structurally
      distinct subtypes, whereas, in the case of GABA(B)Rs, molecular biologists have
      so far identified only one structurally distinct heterodimeric complex whose few
      variants seem unable to explain the pharmacological heterogeneity of GABA(B)Rs
      observed in many functional studies. Both mGluRs and GABA(B)Rs can be localized
      on axon terminals of different neuronal systems as presynaptic autoreceptors and
      heteroreceptors modulating the exocytosis of various transmitters.

PMID- 18064421
TI  - Presynaptic neuropeptide receptors.
AB  - Presynaptic receptors for four families of neuropeptides will be discussed:
      opioids, neuropeptide Y, adrenocorticotropic hormone (ACTH), and orexins.
      Presynaptic receptors for the opioids (micro, delta, kappa, and ORL(1)) and
      neuropeptide Y (Y(2)) inhibit transmitter release from a variety of neurones,
      both in the peripheral and central nervous systems. These receptors, which were
      also identified in human tissue, are coupled to G(i/o) proteins and block voltage
      dependent Ca(2+) channels, activate voltage-dependent K(+) channels, and/or
      interfere with the vesicle release machinery. Presynaptic receptors for ACTH
      (MC(2) receptors) have so far been identified almost exclusively in
      cardiovascular tissues from rabbits, where they facilitate noradrenaline release;
      they are coupled to G(s) protein and act via stimulation of adenylyl cyclase.
      Presynaptic receptors for orexins (most probably OX(2) receptors) have so far
      almost exclusively been identified in the rat and mouse brain, where they
      facilitate the release of glutamate and gamma-aminobutyric acid (GABA); they are
      most probably linked to G(q) and directly activate the vesicle release machinery
      or act via a transduction mechanism upstream of the release process. Agonists and
      antagonists at opioid receptors owe at least part of their therapeutic effects to
      actions on presynaptic receptors. Therapeutic drugs targeting neuropeptide Y and
      orexin receptors and presynaptic ACTH receptors so far are not available.

PMID- 18064422
TI  - Presynaptic modulation by endocannabinoids.
AB  - Modulation of neurotransmitter release by G-protein-coupled receptors (GPCRs) is
      a prominent presynaptic mechanism for regulation of synaptic transmission.
      Activation of GPCRs located at the presynaptic terminal can decrease the
      probability of neurotransmitter release. This presynaptic depression involves
      activation of Gi/o-type G-proteins that mediate different inhibitory mechanisms,
      including inhibition of voltage-gated calcium channels, activation of potassium
      channels, and direct inhibition of the vesicle fusion process. A variety of
      neurotransmitters and modulatory agents can activate GPCRs that produce
      presynaptic depression. Among these are lipid metabolites that serve as agonists
      for GPCRs. The discovery of endocannabinoids and their cognate receptors,
      including the CB1 receptor, has stimulated intense investigation into the
      neurophysiological roles of these lipid metabolites. It is now clear that
      presynaptic depression is the major physiological role for the CB1 receptor.
      Endocannabinoids activate this receptor mainly via a retrograde signaling process
      in which these compounds are synthesized in and released from postsynaptic
      neuronal elements, and travel back to the presynaptic terminal to act on the CB1
      receptor. This retrograde endocannabinoid modulation has been implicated in short
      term synaptic depression, including suppression of excitatory or inhibitory
      transmission induced by postsynaptic depolarization and transient synaptic
      depression induced by activation of postsynaptic GPCRs during agonist treatment
      or synaptic activation. Endocannabinoids and the CB1 receptor also play a key
      role in one form of long-term synaptic depression (LTD) that involves a
      longlasting decrease in neurotransmitter release.

PMID- 18064423
TI  - Presynaptic lonotropic receptors.
AB  - The release of transmitters through vesicle exocytosis from nerve terminals is
      not constant but is subject to modulation by various mechanisms, including prior
      activity at the synapse and the presence of neurotransmitters or neuromodulators
      in the synapse. Instantaneous responses of postsynaptic cells to released
      transmitters are mediated by ionotropic receptors. In contrast to metabotropic
      receptors, ionotropic receptors mediate the actions of agonists in a transient
      manner within milliseconds to seconds. Nevertheless, transmitters can control
      vesicle exocytosis not only via slowly acting metabotropic, but also via fast
      acting ionotropic receptors located at the presynaptic nerve terminals. In fact,
      members of the following subfamilies of ionotropic receptors have been found to
      control transmitter release: ATP P2X, nicotinic acetylcholine, GABA(A),
      ionotropic glutamate, glycine, 5-HT(3), andvanilloid receptors. As these
      receptors display greatly diverging structural and functional features, a variety
      of different mechanisms are involved in the regulation of transmitter release via
      presynaptic ionotropic receptors. This text gives an overview of presynaptic
      ionotropic receptors and briefly summarizes the events involved in transmitter
      release to finally delineate the most important signaling mechanisms that mediate
      the effects of presynaptic ionotropic receptor activation. Finally, a few
      examples are presented to exemplify the physiological and pharmacological
      relevance of presynaptic ionotropic receptors.

PMID- 18064424
TI  - NO/cGMP-dependent modulation of synaptic transmission.
AB  - Nitric oxide (NO) is a multifunctional messenger in the CNS that can signal both
      in antero- and retrograde directions across synapses. Many effects of NO are
      mediated through its canonical receptor, the soluble guanylyl cyclase, and the
      second messenger cyclic guanosine-3',5'-monophosphate (cGMP). An increase of cGMP
      can also arise independently of NO via activation of membrane-bound particulate
      guanylyl cyclases by natriuretic peptides. The classical targets of cGMP are cGMP
      dependent protein kinases (cGKs), cyclic nucleotide hydrolysing
      phosphodiesterases, and cyclic nucleotide-gated (CNG) cation channels. The
      NO/cGMP/cGK signalling cascade has been linked to the modulation of transmitter
      release and synaptic plasticity by numerous pharmacological and genetic studies.
      This review focuses on the role of NO as a retrograde messenger in long-term
      potentiation of transmitter release in the hippocampus. Presynaptic mechanisms of
      NO/cGMP/cGK signalling will be discussed with recently identified potential
      downstream components such as CaMKII, the vasodilator-stimulated phosphoprotein,
      and regulators of G protein signalling. NO has further been suggested to increase
      transmitter release through presynaptic clustering of a-synuclein. Alternative
      modes of NO/cGMP signalling resulting in inhibition of transmitter release and
      long-term depression of synaptic activity will also be addressed, as well as
      anterograde NO signalling in the cerebellum. Finally, emerging evidence for cGMP
      signalling through CNG channels and hyperpolarization-activated cyclic nucleotide
      gated (HCN) channels will be discussed.

PMID- 18064425
TI  - Therapeutic use of release-modifying drugs.
AB  - Presynaptic inhibitory or facilitatory autoreceptors are targets for the
      endogenous neurotransmitter of the respective neuron, and also for exogenous
      agonists, partial agonists and antagonists which can produce pharmacological
      actions through changes in transmitter release. In addition, presynaptic
      inhibitory or facilitatory heteroreceptors can also be acted upon by exogenous
      agonists, partial agonists or antagonists to induce changes in transmitter
      release with useful therapeutic effects. This article summarizes drugs that are
      known or likely to produce their therapeutic effects through presynaptic
      modulation of neurotransmitter release. Included are drugs acting on alpha and
      beta adrenoceptors, dopamine receptors, angiotensin, opioid, cannabinoid, and
      nicotinic acetylcholine receptors. Also discussed are changes in presynaptic
      receptor mechanisms produced by drugs that inhibit transmitter re-uptake.

PMID- 18064426
TI  - Anterolateral ankle impingement: findings and diagnostic accuracy with ultrasound
      imaging.
AB  - OBJECTIVE: The objective was to evaluate the findings and diagnostic accuracy of
      ultrasound in antero-lateral ankle impingement (ALI) with clinical and
      arthroscopic correlation. DESIGN AND PATIENTS: Seventeen elite footballers with
      chronic ankle pain were referred for ultrasound with a clinical diagnosis of ALI
      (n = 8) or a control condition (n = 9; lateral mechanical instability,
      osteochondral defect, intra-articular bodies and osteoarthritis). Ultrasound
      examination included the antero-lateral gutter for abnormal synovial tissue
      (synovitic lesion), lateral ligament integrity, tibiotalar joint and osseous
      spurs of the distal tibia and talus. Ultrasound findings were correlated with
      subsequent arthroscopic appearance. RESULTS: Ultrasound examination detected a
      synovitic mass in the antero-lateral gutter in all 8 footballers with clinical
      ALI (100%) and in 2 patients with a control diagnosis (22%). Arthroscopic
      correlation of antero-lateral synovitis and fibrosis was present in all 10 cases
      (100%). The synovitic lesion was seen at ultrasound as a nodular soft tissue mass
      of mixed echogenicity within the antero-lateral gutter, which extruded anteriorly
      with manual compression of the distal fibula against the tibia. Increased blood
      supply was detected using power Doppler imaging in only 1 patient. The synovitic
      lesion measured >10 mm in its maximum dimension in 7 footballers with clinical
      ALI and <10 mm in the control group. Additional ultrasound findings in patients
      with abnormal antero-lateral synovial tissue included an anterior talofibular
      ligament injury in all patients (n = 10), a tibiotalar joint effusion (n = 6) and
      osseous spurs (n = 4). Antero-lateral synovitic tissue was accurately identified
      at ultrasound in the absence of an effusion (n = 4). No synovitic lesion was
      detected at ultrasound or arthroscopy in the remaining 7 patients with a control
      diagnosis. CONCLUSION: Ultrasound is accurate in detecting synovitic lesions
      within the antero-lateral gutter, demonstrating associated ligamentous injuries
      and in differentiating soft tissue from osseous impingement. Synovitic lesions in
      two control patients suggest that abnormal antero-lateral soft tissue does not
      necessarily imply the presence of symptomatic ALI. Synovitic lesions in excess of
      10 mm were associated with symptoms. Ultrasound will not demonstrate
      osteocartilaginous lesions or stress fractures and may overlook some loose
      bodies. Ultrasound findings together with clinical correlation can be used to
      direct arthroscopic examination and surgical debridement.

PMID- 18064428
TI  - [Recent developments in medical law (April 2007 to October 2007)].

PMID- 18064427
TI  - [Endobronchial ultrasound for diagnosis of the mediastinum].
AB  - The development of endobronchial ultrasound (EBUS) is one of the most important
      advances in bronchoscopy in recent years. Two different techniques are available
      which improve sonographic diagnostics of the mediastinum and staging in patients
      with lung and non-lung cancer. Radial EBUS and the technique of ultrasound
      controlled transbronchial needle aspiration (TBNA) are now routine practice in
      many pulmonary centers. Their clinical application and diagnostic benefit have
      been established in many studies comparing them with conventional radiologic
      methods and other diagnostic procedures. Endobronchial ultrasound as a diagnostic
      tool is expected to gain importance in the near future. Especially the method
      combining EBUS and TBNA may replace more invasive methods such as mediastinoscopy
      for evaluating patients with unknown mediastinal lesions or for staging patients
      with lung cancer.

PMID- 18064429
TI  - [The physician at the start of the 21st century: between Hippocrates and state
      controlled medicine].

PMID- 18064430
TI  - [Catheter-based balloon dilatation of the frontal, maxillary, and sphenoid ostia:
      a new procedure in sinus surgery].
AB  - BACKGROUND: Endoscopic sinus surgery is the procedure of choice for treating
      chronic rhinosinusitis. This paper describes a new minimally invasive method to
      restore ostium patency without removing tissue: the balloon sinuplasty technique.
      PATIENTS AND METHODS: Two patients were treated with the new procedure. One
      patient had her maxillary and sphenoid ostia dilated; the other patient had both
      frontal ostia, both maxillary ostia, and the right sphenoid ostia dilated.
      RESULTS: The balloon dilatations of the ostia were achieved successfully without
      impairing the mucosal circumference. There was no bleeding, and nasal packing was
      not necessary. The postoperative healing process showed no complications.
      CONCLUSION: This paper discusses the advantages and disadvantages as well as the
      indications and contraindications of this method. The balloon sinuplasty
      technique is an easily performed surgery; for selected indications, it seems
      especially suited for opening blocked ostia.

PMID- 18064431
TI  - Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates
      acute and chronic experimental colitis in mice.
AB  - Galectins have recently emerged as central regulators of the immune system. We
      have previously demonstrated that carbohydrate-dependent binding of galectin-2
      induces apoptosis in activated T cells. Here, we investigate the potential
      therapeutic effect of galectin-2 in experimental colitis. Galectin-2 expression
      and its binding profile were determined by immunohistochemistry. Acute and
      chronic colitis was induced by dextran sodium sulfate administration and in a T
      cell transfer colitis model. Apoptosis was assessed by TdT-mediated dUTP-biotin
      nick-end labeling, and cytokine secretion was determined by cytometric bead
      array. We show that galectin-2 was constitutively expressed mainly in the
      epithelial compartment of the mouse intestine and bind to lamina propria
      mononuclear cells. During colitis, galectin-2 expression was reduced, but could
      be restored to normal levels by immunosuppressive treatment. Galectin-2 treatment
      induced apoptosis of mucosal T cells and thus ameliorated acute and chronic
      dextran-sodium-sulfate-induced colitis and in a T-helper-cell 1-driven model of
      antigen-specific transfer colitis. Furthermore, the pro-inflammatory cytokine
      release was inhibited by galectin-2 treatment. In preliminary toxicity studies,
      galectin-2 was well tolerated. Our study provides evidence that galectin-2
      induces apoptosis in vivo and ameliorates acute and chronic murine colitis.
      Furthermore, galectin-2 has no significant toxicity over a broad dose range,
      suggesting that it may serve as a new therapeutic agent in the treatment of
      inflammatory bowel disease.

PMID- 18064432
TI  - [Consistency and change of medical errors in urology].
AB  - BACKGROUND: Whether and how far the ascertainment of medical errors is influenced
      by advances in medicine is a matter of question. MATERIAL AND METHODS: The cases
      of the Expert Committee for Medical Malpractice Claims of the Medical Association
      of North Rhine were reviewed from 1975 to 2005. The results of the first 23 years
      were compared with the last 7 ones. Underlying criteria were the professional
      standards and required care. RESULTS: The number of claims and medical errors
      increased. The rate of medical errors remained approximately constant. The
      spectrum of medical errors remained constant to a large extent. Frequent errors
      were more frequently ascertained. Several errors decreased or increased according
      to medical progress. CONCLUSIONS: To avoid medical errors individual cases should
      be published for learning purposes. Each treatment should be undertaken with
      utmost competence and care.

PMID- 18064433
TI  - [Analyses of the role of immunocytology in the differential diagnosis of patients
      with asymptomatic microhematuria].
AB  - INTRODUCTION: Discriminating between malignant and nonmalignant conditions
      remains a challenge in the evaluation of patients with asymptomatic
      microhematuria. In this prospective study the role of immunocytology in the
      assessment microhematuria was studied. MATERIAL AND METHODS: uCyt is a
      commercially available immunocytological assay based on microscopical detection
      of tumor-associated antigens in urothelial cells by immunofluorescence. Between
      September 2000 and December 2006, 222 consecutive patients with newly diagnosed
      painless microhematuria without prior transitional cell carcinoma were included.
      All urine samples were examined cytologically and immunocytologically. A total of
      211 samples (95%) were assessable. RESULTS: Clinical examination by physical
      examination, cystoscopy, laboratory tests, and imaging yielded bladder cancer in
      ten cases (4%). Further diagnoses were BPH (27%), cystitis (including IC) (12%),
      urolithiasis (9%), urethral or ureteral strictures (6%), papilloma (2%),
      and"further conditions" (16%). In 52 patients (23%) reasons for hematuria were
      not identified. Immunocytology was positive in 8 of 10 bladder tumors (80%) and
      negative in 178 patients with non-tumor-related hematuria (89%). CONCLUSIONS: The
      high sensitivity and good specificity of immunocytology is comparable with that
      reported in the literature despite a very low disease prevalence in this
      population. If assessment of these patients would have only been based on
      immunocytology, 180 costly and invasive diagnostic procedures would have been
      saved, with only 29 individuals (14%) undergoing these examinations
      unnecessarily. The authors conclude that these findings justify further
      investigation of this issue.

PMID- 18064434
TI  - [The history of ureterosigmoidostomy].
AB  - Congenital anomalies like bladder exstrophy were the indication in 1821 to
      implant the ureters into the sigmoid colon for the first time. In 1894 the Maydl
      technique was used more frequently with a postoperative mortality rate of 31%.
      The most important impact for ureterosigmoidostomy came from Robert Coffey in
      1911. Obstruction at the ureterocolic anastomosis, inflammatory complications
      together with severe acidosis, renal insufficiency, and high mortality rates
      however gave way in 1950 to the worldwide success of Bricker's ileal conduit
      although at the same time the technique of ureterosigmoidostomy was perfected by
      Leadbetter, Goodwin, and Hohenfellner. About 25 years later, when the high late
      complication rate of ileal conduits was obvious, the advantages of
      ureterosigmoidostomy were reconsidered and the technique was refined using
      valuable principles of pouch surgery. Today modified ureterosigmoidostomy has a
      strong place among the possibilities of urinary diversion.

PMID- 18064435
TI  - Effects of defoliating insect resistance QTLs and a cry1Ac transgene in soybean
      near-isogenic lines.
AB  - The crystal proteins coded by transgenes from Bacillus thuringiensis (Bt) have
      shown considerable value in providing effective insect resistance in a number of
      crop species, including soybean, Glycine max (L.) Merr. Additional sources of
      soybean insect resistance would be desirable to manage the development of
      tolerance/resistance to crystal proteins by defoliating insects and to sustain
      the deployment of Bt crops. The objective of this study was to evaluate the
      effects and interactions of three insect resistance quantitative trait loci
      (QTLs; QTL-M, QTL-H, and QTL-G) originating from Japanese soybean PI 229358 and a
      cry1Ac gene in a "Benning" genetic background. A set of 16 BC(6)F(2)-derived near
      isogenic lines (NILs) was developed using marker-assisted backcrosses and
      evaluated for resistance to soybean looper [SBL, Pseudoplusia includens (Walker)]
      and corn earworm [CEW, Helicoverpa zea (Boddie)] in field cage, greenhouse, and
      detached leaf assays. Both Bt and QTL-M had significantly reduced defoliation by
      both SBL and CEW and reduced larval weight of CEW. The antibiosis QTL-G had a
      significant effect on reducing CEW larval weight and also a significant effect on
      reducing defoliation by SBL and CEW in some assays. The antixenosis QTL-H had no
      main effect, but it appeared to function through interaction with QTL-M and QTL
      G. Adding QTL-H and QTL-G further enhanced the resistance of the Bt and QTL-M
      combination to CEW in the field cage assay. These results should help guide the
      development of strategies for effective management of insect pests and for
      sustainable deployment of Bt genes.

PMID- 18064436
TI  - Resistance to Erysiphe necator in the grapevine 'Kishmish vatkana' is controlled
      by a single locus through restriction of hyphal growth.
AB  - Vitis vinifera 'Kishmish vatkana', a cultivated grapevine from Central Asia, does
      not produce visible symptoms in response to natural or artificial inoculation
      with the fungus Erysiphe necator Schwein., the casual agent of powdery mildew.
      'Kishmish vatkana' allowed pathogen entry into epidermal cells at a rate
      comparable to that in the susceptible control Vitis vinifera 'Nimrang', but was
      able to limit subsequent hyphal proliferation. Density of conidiophores was
      significantly lower in 'Kishmish vatkana' (33.6+/-8.7 conidiophores mm(-2)) than
      in 'Nimrang' (310.5+/-24.0 conidiophores mm(-2)) by 120 h after inoculation. A
      progeny of 310 plants from a 'Nimrang 'Kishmish vatkana' cross were scored for
      the presence or absence of visible conidiophores throughout two successive
      seasons. Phenotypic segregation revealed the presence of a single dominant allele
      termed Resistance to Erysiphe necator 1 (REN1), which was heterozygous in
      'Kishmish vatkana'. A bulked segregant analysis was carried out using 195
      microsatellite markers uniformly distributed across the entire genome. For each
      marker, association with the resistance trait was inferred by measuring in the
      bulks the ratio of peak intensities of the two alleles inherited from 'Kishmish
      vatkana'. The phenotypic locus was assigned to linkage group 13, a genomic region
      in which no disease resistance had been reported previously. The REN1 position
      was restricted to a 7.4 cM interval by analyzing the 310 offspring for the
      segregation of markers that surrounded the target region. The closest markers,
      VMC9H4-2, VMCNG4E10-1 and UDV-020, were located 0.9 cM away from the REN1 locus.

PMID- 18064437
TI  - [The management of osteoarthritis by general practitioners in Germany: comparison
      of self-reported behaviour with international guidelines].
AB  - BACKGROUND: In most countries, guidelines for the treatment of osteoarthritis
      (OA) are available. However, in Germany, no guideline for the primary care sector
      is available. The care provider of most patients is the general practitioner
      (GP). The aim of the study was to investigate the approaches in diagnosing and
      treating OA of German GPs and to assess adherence to international guidelines.
      METHODS: Cross-sectional study using a structured questionnaire with a random
      sample of 144 GPs. RESULTS: Regarding diagnosis, the importance of X-rays was
      overestimated. Regarding treatment approaches, exercising and weight reduction
      were regarded as primary treatment targets. Pharmacological treatment approaches
      were somewhat guideline oriented, but conservative approaches such as physical
      therapy were overestimated as invasive treatments such as intra-articular
      injections were underestimated in its benefit. CONCLUSION: Establishing a
      guideline specifically for primary care and increasing guideline adherence could
      help to prevent the present overuse of X-rays and the high amount of referrals to
      orthopaedics, save costs and reduce inadequate treatments.

PMID- 18064438
TI  - Pharmacological analysis of the interaction of antimuscarinic drugs at M(2) and
      M(3) muscarinic receptors in vivo using the pithed rat assay.
AB  - Muscarinic receptor antagonists form the mainstay of the therapeutic options for
      airway, bladder, and gastrointestinal smooth muscle disorders. Both M(2) and M(3)
      muscarinic receptors are involved in mediating smooth muscle contractility,
      although the relative functional contribution of each subtype, especially in the
      disease state, is unclear. Because the potency and selectivity of compounds for a
      given receptor in an in vivo setting can be dissimilar to that observed in an in
      vitro system, we developed an in vivo assay to simultaneously determine the
      absolute potency and selectivity of muscarinic receptor antagonists at M(2) and
      M(3) receptors using the pithed rat. Methacholine (MCh)-induced bradycardia and
      depressor responses were used as surrogate functional endpoints for M(2) and M(3)
      receptor activation, respectively. The influence of the muscarinic antagonists,
      tolterodine, oxybutynin, darifenacin, Ro 320-6206, solifenacin, or tiotropium on
      the MCh-induced responses were studied. The estimated DR(10) values (dose
      producing a tenfold shift in the MCh curve) of tolterodine, oxybutynin,
      darifenacin, Ro 320-6206, solifenacin, and tiotropium for the M(2) muscarinic
      receptor-mediated bradycardia were 0.22, 1.18, approximately 2.6, 0.025, 0.40,
      and 0.0026 mg/kg, respectively, and 0.14, 0.18, 0.11, 3.0, 0.18, and 0.0017
      mg/kg, respectively, for the M(3) muscarinic receptor-mediated depressor
      response. In a separate set of experiments, a single intravenous dose of
      tiotropium was administered before a MCh curve at 1, 3, 6, or 9 h to determine if
      tiotropium exhibited time-dependent selectivity for the M(3) receptor as has been
      reported from in vitro studies. The results indicate a slight preference of
      tiotropium for the M(3) receptor at later time points. The pithed rat assay may
      serve useful for elucidating the functional contribution of M(2) and M(3)
      receptors to the in vivo pharmacological effects of antagonists in disease animal
      models.

PMID- 18064439
TI  - Effects of propofol on the leukocyte nitric oxide pathway: in vitro and ex vivo
      studies in surgical patients.
AB  - This study was designed to evaluate the mechanism by which propofol modifies
      leukocyte production of nitric oxide (NO) in humans. In vitro experiments used
      whole blood from healthy volunteers (n = 10 samples/experiment). Ex vivo
      experiments studied the effects of an intravenous dose of 2.5 mg propofol per
      kilogram body weight followed by intravenous infusion of 4 mg kg(-1) h(-1) in
      surgical patients in ASA class I or II (n = 20). In whole blood, neutrophils and
      plasma, we measured NO production and the activities of the enzymes nitric oxide
      synthase [inducible (iNOS) and constitutive (cNOS)] and cyclooxygenase
      [constitutive (COX-1) and inducible (COX-2)]. Concentrations of interleukins (IL
      1beta, IL-6, and IL-10) and tumor necrosis factor-alpha (TNFalpha) were measured
      in plasma. In blood from healthy donors, propofol increased NO production and
      cNOS activity. The concentration of propofol that increased NO production by 50%
      (EC(50)) was 23.5 microM, and the EC(50) of propofol for cNOS was 18.6 microM. In
      blood from surgical patients, propofol increased NO production by 52% and cNOS
      activity by 57%. Propofol inhibited iNOS activity in vitro; the concentration
      that reduced activity by 50% (IC(50)) was 19.9 microM. In surgical patients
      propofol inhibited iNOS activity by 53%. COX-1 and COX-2 activities were
      inhibited in vitro (IC(50) 32.6 and 187 microM, respectively) and in surgical
      patients (53 and 81% inhibition, respectively). Plasma concentrations of IL
      1beta, IL-6, and TNFalpha were significantly reduced in surgical patients (32,
      23, and 21% inhibition, respectively). None of these parameters were modified in
      a group of patients (n = 10) anesthetized with sevoflurane. We conclude that
      propofol stimulated constitutive NO production and inhibited inducible NO
      production, possibly by curtailing the stimulation of iNOS by inflammatory
      mediators in surgical patients.

PMID- 18064441
TI  - Birthday chromatography challenge.

PMID- 18064440
TI  - Evaluating the utility of administering a reaction time task in an ecological
      momentary assessment study.
AB  - RATIONALE: Cognitive processes underlying drug use have typically been assessed
      in laboratory settings. More detailed and ecologically valid data may be possible
      if assessments were conducted in an ecological momentary assessment (EMA)
      setting. OBJECTIVES: We evaluated the feasibility and utility of administering a
      reaction time task on a hand-held computer (personal digital assistant, PDA) in
      an EMA setting. MATERIALS AND METHODS: Twenty-two smokers and 22 non-smokers
      carried around the PDA for 1 week as they went about their daily lives. They were
      beeped at random times four times per day (random assessments, RAs). Participants
      were also instructed to press an "anxiety assessment" (AA) button on the PDA
      whenever they felt suddenly anxious. At each assessment (RA, AA), participants
      responded to items assessing subjective, pharmacological, and contextual
      variables, and subsequently completed a Stroop task (classic-Stroop, emotional
      Stroop, or smoking-Stroop task). RESULTS: Participants responded to 81.2% of RAs,
      completed assessments in an average of 4.44 min, reported no interruptions on the
      majority of assessments (62.4%), and produced data with adequate reliability.
      Using generalized estimating equation (GEE) analyses, age was associated with the
      classic-Stroop effect, state anxiety was associated with the emotional-Stroop
      effect, and Fagerstrom Test for Nicotine Dependence scores were associated with
      the smoking-Stroop effect. CONCLUSIONS: The study provided evidence for the
      feasibility and utility of the approach.

PMID- 18064442
TI  - Neuronal activity related to anticipated and elapsed time in macaque
      supplementary eye field.
AB  - It is essential to sense anticipated and elapsed time in our daily life. Several
      areas of the brain including parietal cortex, prefrontal cortex, basal ganglia
      and olivo-cerebellar system are known to be related to this temporal processing.
      We now describe a number of cells in the supplementary eye field (SEF) with
      phasic, delay activity and postdelay activity modulation that varied with the
      length of the delay period. This variation occurred in two manners. First, cells
      became active with the shorter delay periods (GO signal presented earlier). We
      call these cells "short-delay cells". Second, cells became active with the longer
      delay periods (GO signal presented later). We call these cells "long-delay
      cells". However, such changed neuronal activity did not correlate with reaction
      time. These results suggest that the delay-dependent activity may reflect
      anticipated and elapsed time during performance of a delayed saccadic eye
      movement.

PMID- 18064443
TI  - Strategy adoption and locomotor adjustment in obstacle clearance of newly walking
      toddlers with Down syndrome after different treadmill interventions.
AB  - This study investigated how newly walking toddlers with Down syndrome (DS), after
      different treadmill interventions, adopted clearance strategies and modified
      anticipatory locomotor adjustment patterns to negotiate an obstacle in their
      travel path. Thirty infants with DS (about 10 months of age) were recruited and
      randomly assigned to either a lower-intensity, generalized (LG) treadmill
      training group, or a higher-intensity, individualized (HI) treadmill training
      group. Thirteen in each group completed a one-year-gait follow-up after the
      treadmill intervention. Initially, both groups chose to either crawl or walk over
      an obstacle. However, walking over the obstacle became their preferred clearance
      strategy over the course of the gait follow-up even though the height of the
      obstacle increased from visit to visit. The HI group used the strategy of walking
      over the obstacle at a considerably higher percentage than the LG group within 6
      months after the training. When approaching the obstacle, both groups started to
      show consistent anticipatory locomotor adjustments about 6 months after the
      training. Both groups decreased velocity, cadence and step length, and increased
      step width at the last three pre-obstacle steps. It was concluded that the
      retention of the HI training effects led the HI group to predominantly walk over
      an obstacle earlier than the LG group within 6 months after treadmill
      intervention, and the two groups produced similar anticipatory locomotor
      adjustments in the last three steps before negotiating the obstacle.

PMID- 18064444
TI  - Artemisinin and CYP2A6 activity in healthy subjects.
AB  - OBJECTIVE: To investigate whether the antimalarial drug artemisinin affects
      CYP2A6 activity in healthy subjects and to compare the utility of coumarin and
      nicotine as in vivo probe compounds for CYP2A6. METHODS: Twelve healthy male
      Vietnamese subjects were given coumarin or nicotine in randomized sequence before
      and after 5 days of a repeated oral administration of artemisinin during two
      different treatment periods 1 month apart. Sequential blood samples were drawn at
      baseline 7 days prior to artemisinin treatment and on the first and fifth day of
      artemisinin treatment during both treatment periods. Plasma concentrations of 7
      hydroxycoumarin glucuronide (7-OHCG), nicotine, cotinine and artemisinin were
      analysed by high-performance liquid chromatography and those of coumarin and 7
      hydroxycoumarin (7-OHC) were determined by liquid chromatography-tandem mass
      spectrometry. Urine, collected in two time intervals on the days of coumarin
      intake, was treated with beta-glucuronidase and analysed for 7-OHC levels.
      RESULTS: Artemisinin AUC(0-infinity) values decreased significantly to 23% [95%
      confidence interval (CI) 18%-28%] on the fifth day of artemisinin administration
      as compared with the first. The sum of renally excreted 7-OHC and 7-OHCG
      increased by 1.55-fold (adjusted 95% CI 1.08-2.23) in the 3- to 8-h interval
      compared to baseline 7 days before. The 7-OHCG/7-OHC plasma AUC(0-infinity) ratio
      increased by 1.72-fold (adjusted 95% CI 1.16-2.54) following 5 days of
      artemisinin intake. There was no significant change in the cotinine/nicotine
      AUC(0-11 hr) ratio between study days. CONCLUSION: Artemisinin significantly
      increased the sum of renally excreted 7-OHC and 7-OHCG in one of the two
      collection intervals, suggesting an induction of CYP2A6. A significant increase
      in the 7-OHCG to 7-OHC AUC(0-infinity) ratio indicates artemisinin to be an
      inducer of glucuronidation.

PMID- 18064445
TI  - Ruptured, dissecting posterior inferior cerebellar artery aneurysms: endovascular
      treatment without parent vessel occlusion.
AB  - INTRODUCTION: Treatment of a dissecting aneurysm of the medullary segments of the
      posterior inferior cerebellar artery (PICA) usually entails trapping of the
      diseased arterial segment with possible sacrifice of brainstem perforators. The
      goal of the work was to review our experience with selective coiling of ruptured,
      dissecting aneurysms of the anterolateral segments of the PICA without parent
      vessel occlusion. METHODS: Eleven consecutive patients (9 women, 2 men, mean age
      47.2 years) were retrospectively reviewed from a prospectively acquired
      neuroradiological database. On admission three patients had Hunt and Hess (HH)
      grade I, three HH grade II, two HH grade III, and one HH grade IV. Outcome was
      evaluated according to the modified Rankin scale (mRS) score. Follow-up
      (mean:19.4 months) consisted of magnetic resonance angiography and/or digital
      subtraction angiography in ten patients. RESULTS: Ten patients had mRS score 0
      and one mRS score 2. No treatment failure occurred. The aneurysm was completely
      occluded in seven patients, a neck residue was present in two, and a loose coil
      mesh was present in two. Recurrence occurred in three patients, and all were
      successfully retreated for a total of 13 procedures. Procedure-related
      complications were all without clinical consequences and included a coil
      perforation in one procedure and stagnant filling of the parent vessel in six
      procedures. PICA occlusion did not occur in any patient. CONCLUSION: Coiling of
      ruptured, isolated dissecting aneurysms of the PICA without parent vessel
      occlusion is feasible, relatively safe and effective in preventing early/medium
      term rebleeding. A strict angiographic follow-up program is, however, necessary
      to detect recurrence.

PMID- 18064446
TI  - Treatment of renal calculi by lithotripsy: minimizing short-term shock wave
      induced renal damage by using antioxidants.
AB  - Treatment with extracorporeal shock wave lithotripsy (ESWL), the preferred method
      of treating kidney stones <3 cm in size, has been shown to induce silent and
      often self-limiting acute and chronic lesions in the kidneys and adjacent organs.
      We conducted a randomized clinical trial to determine whether ESWL produces
      ischaemia and reperfusion injury in the kidneys and whether oral administration
      of antioxidants reduces the degree of short-term renal injury in patients treated
      with ESWL. The study included 120 patients with renal stones (1-3 cm in size)
      treated with ESWL. The patients were divided into three groups--patients in group
      A (n=39) served as a control group and were not given any antioxidants; patients
      in group B (n=41) were given two capsules of antioxidants "Nature Made R: " 2 h
      before ESWL, and 2 and 8 h after ESWL; and patients in group C (n=40) were given
      two capsules of the antioxidants 2 and 8 h after ESWL. Double 'J' stents were
      inserted in patients before treatment with ESWL. Blood and urine samples were
      obtained from all patients just before the start of treatment with ESWL, and at 2
      and 24 h and on 7th and 28th day after ESWL. Serum levels of malondialdehyde
      (MDA), alpha-tocopherol, cholesterol, albumin and ascorbic acid, and alpha
      tocopherol/cholesterol ratio were determined. Urinary levels of albumin and
      beta(2) microglobulin were also determined as measures of renal tubular injury.
      At 24 h after ESWL, patients given antioxidants (groups B + C) had significantly
      reduced mean serum concentration of MDA (P<0.001); higher levels of serum
      ascorbic acid (P<0.001) and serum albumin (P<0.001); lower alpha
      tocopherol/cholesterol ratio, lower urinary albumin and beta(2 )microglobulin
      levels compared with patients who did not receive antioxidants (group A). These
      findings suggest that treatment with ESWL generates free radicals through
      ischaemic/reperfusion injury mechanism, and that oral administration of
      antioxidant may protect these patients from short term renal injury caused by
      ESWL.

PMID- 18064448
TI  - Protection of liposomes against fusion during drying by oligosaccharides is not
      predicted by the calorimetric glass transition temperatures of the dry sugars.
AB  - Sugars play an important role in the desiccation tolerance of most anhydrobiotic
      organisms. It has been shown in previous studies that different structural
      families of oligosaccharides have different efficacies to interact with
      phospholipid headgroups and protect membranes from solute leakage during drying.
      Here, we have compared three families of linear oligosaccharides (fructans
      (inulins), malto-oligosaccharides, manno-oligosaccharides) for their chain-length
      dependent protection of egg phosphatidylcholine liposomes against membrane
      fusion. We found increased protection with chain length up to a degree of
      polymerization (DP) of 5 for malto-oligosaccharides, and a decrease for inulins
      and manno-oligosaccharides. Differential scanning calorimetry measurements showed
      that for all sugars the glass transition temperature (T(g)) increased with DP,
      although to different degrees for the different oligosaccharide families. Higher
      T(g) values resulted in reduced membrane fusion only for malto-oligosaccharides
      below DP5. Contrary to expectation, for inulins, manno-oligosaccharides and malto
      oligosaccharides of a DP above five, fusion increased with increasing T(g),
      indicating that other physical parameters are more important in determining the
      ability of different sugars to protect membranes against fusion during drying.
      Further research will be necessary to experimentally define such parameters.

PMID- 18064447
TI  - The role of exosomes in the processing of proteins associated with
      neurodegenerative diseases.
AB  - Exosomes are small membranous vesicles secreted by a number of cell types and can
      be isolated from conditioned cell media or bodily fluids such as urine and
      plasma. Exosome biogenesis involves the inward budding of multivesicular bodies
      (MVB) to form intraluminal vesicles (ILV). When fused with the plasma membrane,
      the MVB releases the vesicles into the extracellular environment as exosomes.
      Proposed functions of these vesicles include roles in cell-cell signalling,
      removal of unwanted proteins, and the transfer of pathogens between cells, such
      as HIV-1. Another such pathogen which exploits this pathway is the prion, the
      infectious particle responsible for the transmissible neurodegenerative diseases
      such as Creutzfeldt-Jakob disease (CJD) of humans or bovine spongiform
      encephalopathy (BSE) of cattle. Interestingly, this work is mirrored by studies
      on another protein involved in neurodegenerative disease, the amyloid precursor
      protein (APP) which is associated with Alzheimer's disease (AD). Recent work has
      found APP proteolytic fragments in association with exosomes, suggesting a common
      pathway previously unknown for proteins associated with neurodegenerative
      diseases. This review will be discussing the current literature regarding the
      role of exosomes in secretion of the proteins, PrP and APP, and the subsequent
      implications for neurodegenerative disease.

PMID- 18064449
TI  - Neurotoxicity in Alzheimer's disease: is covalently crosslinked A beta
      responsible?
AB  - Alzheimer's disease is the most common form of dementia in the elderly, and is
      characterised by extracellular amyloid plaques composed of the beta-amyloid
      peptide (A beta). However, disease progression has been shown to correlate more
      closely with the level of soluble A beta oligomers. Recent evidence suggests that
      these oligomers are covalently crosslinked, possibly due to the interaction of A
      beta with redox-active metal ions. These findings offer new avenues for the
      treatment and prevention of disease, by modulating metal binding or preventing
      the formation of neurotoxic A beta oligomers.

PMID- 18064450
TI  - Structure and dynamics of the antifungal molecules Syringotoxin-B and
      Syringopeptin-25A from molecular dynamics simulation.
AB  - The phytopathogen Pseudomonas syringae pv. syringae produces toxic cyclic
      lipodepsipeptides (CLPs): nona-peptides and syringopeptins. All CLPs inhibit the
      growth of many fungal species, including human pathogens, although different
      fungi display different degrees of sensitivity. The best studied CLPs are
      Syringomycin-E (SR-E), Syringotoxin-B (ST-B) and Syringopeptin-25A (SP-25A).
      Their biological activity is affected by membrane composition and their
      structural differences. We previously (Matyus et al. in Eur Biophys J 35:459-467,
      2006) reported the molecular features and structural preferences of SR-E in water
      and octane environments. Here we investigate in atomic detail the molecular
      features of the two other main CLP components, ST-B and SP-25A, in water and
      octane by 200 ns molecular dynamics simulations (MD), using distance restraints
      derived from NMR NOE data (Ballio et al. in Eur J Biochem 234:747-758, 1995). We
      have obtained three-dimensional models of ST-B and SP-25A CLPs in different
      environments. These models can now be used as a basis to investigate the
      interactions of ST-B and SP-25A with lipid membranes an important further step
      towards a better understanding of the antifungal and antibacterial activity of
      these peptides.

PMID- 18064452
TI  - Formation of volatile sulfur compounds and metabolism of methionine and other
      sulfur compounds in fermented food.
AB  - The formation of volatile sulfur compounds (VSC) in fermented food is a subject
      of interest. Such compounds are essential for the aroma of many food products
      like cheeses or fermented beverages, in which they can play an attractive or a
      repulsive role, depending on their identity and their concentration. VSC
      essentially arise from common sulfur-bearing precursors, methionine being the
      most commonly found. In the first section of this paper, the main VSC found in
      cheese, wine, and beer are reviewed. It is shown that a wide variety of VSC has
      been evidenced in these food products. Because of their low odor threshold and
      flavor notes, these compounds impart essential sensorial properties to the final
      product. In the second section of this review, the main (bio)chemical pathways
      leading to VSC synthesis are presented. Attention is focused on the
      microbial/enzymatic phenomena-which initiate sulfur bearing precursors
      degradation-leading to VSC production. Although chemical reactions could also
      play an important role in this process, this aspect is not fully developed in our
      review. The main catabolic pathways leading to VSC from the precursor methionine
      are presented.

PMID- 18064451
TI  - IL4 in the 5q31 context: association studies of type 1 diabetes and rheumatoid
      arthritis in the Spanish population.
AB  - IL4, the gene coding the prototypic Th2 cytokine, has been frequently studied in
      the context of several inflammatory conditions, but conclusive results have not
      been obtained. This gene is located in the 5q31-33 complex genetic region, which
      shows some susceptibility factors to type 1 diabetes (T1D) and rheumatoid
      arthritis (RA) among other inflammatory conditions. Our aim was to assess the
      involvement on T1D and RA of IL4 polymorphisms considered individually and in
      combination with other polymorphisms in 5q31-33, specifically in the OCTN locus,
      where the L503F polymorphism has been associated with Crohn's disease and other
      Th1 diseases. We performed a case-control study including 316 T1D patients, 599
      RA patients and 540 healthy controls, all of them corresponding to white Spanish
      individuals. The IL4 single-nucleotide polymorphisms (SNPs) -590C/T (rs2243250)
      and the OCTN1 exonic SNP L503F (rs1050152) were analysed in all samples.
      Frequency comparisons of -590C/T and stratified analysis including both cited
      SNPs were performed using chi-square tests. The -590C/T IL4 SNP was not found
      associated with T1D or RA when individual analyses were performed. However, a
      significant association with T1D emerged after stratification by L503F [p=0.02,
      odds ratio=1.95, 95% CI=1.07-3.55]. The location of the IL4 gene in the complex
      5q31-33 genetic region, which contains many genes involved in immunological
      responses and presents linkage disequilibrium extended along many kilobases,
      makes necessary to interpret cautiously the previous IL4-association studies.

PMID- 18064453
TI  - High-density fermentation of microalga Chlorella protothecoides in bioreactor for
      microbio-diesel production.
AB  - Agal-fermentation-based microbio-diesel production was realized through high-cell
      density fermentation of Chlorella protothecoides and efficient
      transesterification process. Cell density achieved was 16.8 g l(-1) in 184 h and
      51.2 g l(-1) in 167 h in a 5-l bioreactor by performing preliminary and improved
      fed-batch culture strategy, respectively. The lipid content was 57.8, 55.2, and
      50.3% of cell dry weight from batch, primary, and improved fed-batch culture in 5
      l bioreactor. Transesterification was catalyzed by immobilized lipase, and the
      conversion rate reached up to 98%. The properties of biodiesel from Chlorella
      were comparable to conventional diesel fuel and comply with US standard for
      Biodiesel. In a word, the approach including high-density fermentation of
      Chlorella and enzymatic transesterification process were set up and proved to be
      a promising alternative for biodiesel production.

PMID- 18064454
TI  - Production of Chryseobacterium proteolyticum protein-glutaminase using the twin
      arginine translocation pathway in Corynebacterium glutamicum.
AB  - The protein glutaminase (PG) secreted by the Gram-negative bacterium
      Chryseobacterium proteolyticum can deamidate glutaminyl residues in several
      substrate proteins, including insoluble wheat glutens. This enzyme therefore has
      potential application in the food industry. We assessed the possibility to
      produce PG containing a pro-domain in Corynebacterium glutamicum which we have
      successfully used for production of several kinds of proteins at industrial
      scale. When it was targeted to the general protein secretion pathway (Sec) via
      its own signal sequence, the protein glutaminase was not secreted in this strain.
      In contrast, we showed that pro-PG could be efficiently produced using the
      recently discovered twin-arginine translocation (Tat) pathway when the typical
      Sec-dependent signal peptide was replaced by a Tat-dependent signal sequence from
      various bacteria. The accumulation of pro-PG in C. glutamicum ATCC13869 reached
      183 mg/l, and the pro-PG was converted to an active form as the native one by SAM
      P45, a subtilisin-like serine protease derived from Streptomyces albogriseolus.
      The successful secretion of PG via this approach confirms that the Tat pathway of
      C. glutamicum is an efficient alternative for the industrial-scale production of
      proteins that are not efficiently secreted by other systems.

PMID- 18064455
TI  - Optimization of nutrient components for enhanced phenazine-1-carboxylic acid
      production by gacA-inactivated Pseudomonas sp. M18G using response surface
      method.
AB  - The nutritional requirements for phenazine-1-carboxylic acid (PCA) production
      using Pseudomonas sp. M18G, a gacA chromosomal-inactivated mutant of the strain
      M18, with a high PCA yield, were optimized statistically in shake flask
      experiments. Based on a single-factor experiment design, we implemented the two
      level Plackett-Burman (PB) design with 11 variables to screen medium components
      that significantly influence PCA production. Soybean meal, glucose, soy peptone,
      and ethanol were identified as the most important significant factors (P < 0.05).
      Response surface methodology based on the Center Composite Design (CCD) was
      applied to determine these factors' optimal levels and their mutual interactions
      between components for PCA production. The predicted results showed that 1.89 g
      l(-1) of PCA production was obtained after a 60-h fermentation period, with
      optimal concentrations of soybean meal powder (33.4 g l(-1)), glucose (12.7 g l(
      1)), soy peptone (10.9 g l(-1)), and ethanol (13.8 ml l(-1)) in the flask
      fermentations. The validity of the model developed was verified, and the optimum
      medium led to a maximum PCA concentration of 2.0 g l(-1), a nearly threefold
      increase compared to that in the basal medium. Furthermore, the experiment was
      scaled up in the 10 l fermentor and 2 g l(-1) PCA productions were achieved in 48
      h based on optimization mediums which further verified the practicability of this
      optimum strategy.

PMID- 18064456
TI  - What is the role of FDG-PET in the initial staging of breast cancer?

PMID- 18064457
TI  - Comparison of bioabsorbable interference screws and posts for distal fixation in
      anterior cruciate ligament reconstruction.
AB  - Comparison of the results of bioabsorbable interference screws and posts for
      hamstring graft distal fixation in ACL reconstructions are presented. The results
      of 20 patients with bioabsorbable screws were compared to 22 patients with posts.
      The assessement was based on Lysholm-Gillquist and Marshall scores and the KT
      1000 device. In the study group the points gained were 38.9 in the Lysholm
      Gillquist and 12.89 in the Marshall scale. The average KT-1000 difference was
      2.46 mm. In the control group the points gained were 32.93 in the Lysholm
      Gillquist and 11.47 in the Marshall scale. The average KT-1000 difference was 2.5
      mm. There were 14 patients in the study group with interference screw problems;
      in 2 the implants were removed. (1) There are no differences in outcome using
      bioabsorbable interference screws and posts for distal fixation of hamstring ACL
      grafts. (2) The lack of bioabsorbtion with poly L-lactide interference screws is
      frequent and causes problems.

PMID- 18064458
TI  - Beta-Thalassemia a surprising reason for anaemia in North Poland children.

PMID- 18064459
TI  - Progressive multifocal leukoencephalopathy: report of three cases in HIV-negative
      hematological patients and review of literature.
AB  - Progressive multifocal leukoencephalopathy (PML) is a central nervous system
      (CNS) disease usually observed in immunodeficient patients, especially human
      immunodeficiency virus (HIV)-positive, caused by John Cunningham virus. This
      infectious complication has been described in many HIV-negative hematological
      patients, especially affected by lymphoproliferative diseases. PML has been
      observed after both chemotherapy and bone marrow transplantation and, recently,
      in association with rituximab. Diagnosis can be complicated, and often a CNS
      biopsy is required. Current treatment approaches are not effective in both HIV
      positive and HIV-negative patients, and the outcome remain very poor in the
      majority of cases, even after combination therapies. We report three cases of PML
      in hematological patients, treated respectively with conventional chemotherapy
      and autologous and haploidentical transplantation, and review the literature on
      PML. All of them received rituximab, which has recently been in the focus of a
      Food and Drug Administration warning.

PMID- 18064460
TI  - Tailored preoperative treatment of locally advanced triple negative (hormone
      receptor negative and HER2 negative) breast cancer with epirubicin, cisplatin,
      and infusional fluorouracil followed by weekly paclitaxel.
AB  - BACKGROUND: No specific treatment guidelines are available for triple-negative
      breast cancers, defined by a lack of expression of estrogen (ER), progesterone
      (PgR), and HER2 receptors. PATIENTS AND METHODS: We investigated in patients with
      T2-T3 N0-3 ER, PgR <10% and HER2 negative breast cancers the activity both in
      terms of pathological (pCR) and objective responses of four courses of cisplatin
      containing chemotherapy (ECF, epirubicin, cisplatin, and fluorouracil as
      continuous infusion) followed by three courses of weekly paclitaxel. Adjuvant
      metronomic chemotherapy including cyclophosphamide and methotrexate for 4-6
      months was administered. RESULTS: Thirty patients are evaluable. Median age was
      41 years (28-64 years). Twenty-three of 25 evaluable tumors stained positively
      for epidermal growth factor receptor. An objective response, either complete and
      partial, was observed in 26 patients (86, 95% CI 69.3-96.2%). and a pCR was
      obtained in 12 patients (40, 95% CI 22.7-59.4%). Two patients progressed during
      paclitaxel. Negative axillary nodes were found in 80% (95% CI 61.4-92.3%) of
      patients at surgery. Twenty-six patients (86, 95% CI 61.4-92.3%) underwent breast
      conserving surgery. Grade >2 non-hematological toxicity was observed in three and
      two patients during ECF and paclitaxel, respectively. The 2-year disease free
      survival (DFS) was 87.5% (95% CI 74.7-100%). No significant correlation was
      observed between EGFR staining and either pCR or DFS. CONCLUSIONS: Preoperative
      cisplatin containing chemotherapy followed by paclitaxel induced an high pCR rate
      in a population of triple-negative breast cancer. The impact of this schedule on
      long-term outcome should be investigated in larger series.

PMID- 18064461
TI  - Prompt and sustained response of a steroid-refractory autoimmune hemolytic anemia
      to a rituximab-based therapy in a chronic lymphocytic leukemia patient.
AB  - INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is a rare and potentially life
      threatening event which may complicate the course of chronic lymphocytic leukemia
      (CLL) at any time and steroid-refractory AIHA of CLL poses a therapeutic
      challenge for physicians. Here, we report the safety and efficacy of a rituximab
      containing regimen in a CLL patient with steroid- and IVIg-refractory AIHA. CASE
      REPORT: A 57-year- old man affected by CLL, presented with fatigue, dyspnoea,
      tachycardia and jaundice. His physical examination revealed overt jaundice,
      hepato- and splenomegaly, and enlargement of lymph nodes in all superficial
      sites. The blood chemistry showed severe anemia (Hb value 3.9 g/dL), high white
      blood cell count (89 x 10(9)/L), altered hemolysis markers and direct
      antiglobulin test (DAT) was positive for both complement and IgG. The patient
      failed to respond to both a 4-day course of high-dose dexamethasone IV (40
      mg/day) and intravenous immunoglobulin (IVIg) (1 g/kg/day x 2 days). Thus, a
      schedule containing rituximab (375 mg/m(2) day +1), cyclophosphamide (750 mg/m(2)
      day +2) and prednisone (60 mg/m(2) from day +1 to day +7) (R-CP) were
      administered. Four cycles, repeated every 4 weeks, were administered. After 4
      days from the infusion of this schedule, the patient showed a marked reduction of
      the lymphocytosis, and the hemoglobin level started to increase. No rituximab
      related side effects were recorded. At the end of treatment DAT became negative
      and patient achieved a nodular Partial Remission (nPR). CONCLUSION: Our data
      showed the safety and efficacy of a rituximab-containing regimen in a life
      threatening CLL-related AIHA, refractory to steroid and IVIg therapy. This
      schedule has allowed the patient to obtain a prompt and dramatic rise in
      hemoglobin level and a response to both AIHA and CLL.

PMID- 18064462
TI  - Logistic regression analysis for febrile neutropenia (FN) induced by docetaxel in
      Japanese cancer patients.
AB  - PURPOSE: Fever occurring in a neutropenic patient remains a common life
      threatening complication of cancer chemotherapy, and febrile neutropenia (FN) is
      recognized as a dose-limiting factor (DLF) in cancer chemotherapy. The aim of
      this study is to evaluate the significant covariate associated with the risk of
      FN occurrence in Japanese patients. METHODS: A stepwise logistic regression was
      conducted using data from Japanese cancer patients treated with docetaxel. Based
      on those results, an equation was established which predicts the probability of
      FN occurrence. RESULTS: From the result of a stepwise multivariate logistic
      regression analysis, performance status factor (PS*), which is set to 1 if
      performance status factor is 2 or 3, and to 0 otherwise and area under the plasma
      concentration versus time curve (AUC) were selected as covariates significantly
      associated (p < 0.05) with FN occurrence. The obtained equation to predict the
      probability (P) of docetaxel-induced FN occurrence is P = 1/[1 + exp{-(1.29 x AUC
      + 1.41 x PS* -3.52)}]. A receiver operating characteristic (ROC) curve analysis
      revealed that the best cut-off value of FN probability to differentiate between
      the presence and absence of FN was 0.61. CONCLUSIONS: An equation was developed
      to predict the probability of FN occurrence for Japanese patients treated with
      docetaxel. It was found that FN may not occur when the probability of FN
      occurrence calculated by the predictive equation is less than 0.61. Therefore,
      the predictive equation for FN occurrence may be used for selecting the
      appropriate dose to avoid the occurrence of FN.

PMID- 18064463
TI  - Mechanisms of enhanced tumoricidal efficacy of multiple small dosages of
      ranpirnase, the novel cytotoxic ribonuclease, on lung cancer.
AB  - PURPOSE: The effect of multiple small dosages of the cytotoxic RNase, ranpirnase
      (ONCONASE, ONC), on lung cancer was studied. The possible mechanisms for the
      enhanced tumoricidal efficacy of multiple small dosages of ONC were also
      investigated. METHODS: Hematoxylin and eosin staining, TUNEL labeling, and
      caspase-3-antibody labeling were used for in vivo analysis of apoptosis. A growth
      delay assay was applied to detect the therapeutic potential of small and multiple
      dosages of ONC in vivo. ONC-induced changes in blood flow in A549 tumors and the
      kidney were measured non-invasively by dynamic contrast enhanced magnetic
      resonance imaging (DCE-MRI). RESULTS: In cell culture studies, ONC significantly
      inhibited tumor growth of A549 human NSCLC cells without damaging non-cancerous
      cells (HLF-1 human lung fibroblast). Multiple small dosages of ONC significantly
      prolonged tumor growth delay of A549 tumors, with increased apoptosis in vivo
      from 0.5 +/- 0.3 to 70.1 +/- 1.1% (by TUNEL labeling, N = 3, P < 0.05).
      Interestingly, multiple small doses of ONC were more effective than a single
      large dose for the inhibition of tumor growth with reduced side effect. Using non
      invasive DCE-MRI methods, we found that the mean of the K (trans) median values
      increased to 49.3 +/- 7.5% from the pre-ONC values by ONC (N = 4 mice, P < 0.05).
      A subsequent T (1) map of the kidney showed that T (1) values were temporarily
      decreased for up to 2 days (however, fully recovered approximately 4 days post
      treatment). CONCLUSIONS: Multiple small dosages of ONC significantly inhibited
      tumor growth of A549 NSCLC cells in vivo, with markedly increased apoptosis. This
      investigation suggests important potential clinical uses of ONC for the treatment
      of NSCLC cancer patients.

PMID- 18064464
TI  - Analytic steady-state space use patterns and rapid computations in mechanistic
      home range analysis.
AB  - Mechanistic home range models are important tools in modeling animal dynamics in
      spatially complex environments. We introduce a class of stochastic models for
      animal movement in a habitat of varying preference. Such models interpolate
      between spatially implicit resource selection analysis (RSA) and advection
      diffusion models, possessing these two models as limiting cases. We find a closed
      form solution for the steady-state (equilibrium) probability distribution u using
      a factorization of the redistribution operator into symmetric and diagonal parts.
      How space use is controlled by the habitat preference function w depends on the
      characteristic width of the animals' redistribution kernel: when the
      redistribution kernel is wide relative to variation in w, u proportional, variant
      w, whereas when it is narrow relative to variation in w, u proportional, variant
      w (2). In addition, we analyze the behavior at discontinuities in w which occur
      at habitat type boundaries, and simulate the dynamics of space use given two
      dimensional prey-availability data, exploring the effect of the redistribution
      kernel width. Our factorization allows such numerical simulations to be done
      extremely fast; we expect this to aid the computationally intensive task of model
      parameter fitting and inverse modeling.

PMID- 18064465
TI  - An age-and-cyclin-structured cell population model for healthy and tumoral
      tissues.
AB  - We present a nonlinear model of the dynamics of a cell population divided into
      proliferative and quiescent compartments. The proliferative phase represents the
      complete cell cycle (G (1)-S-G (2)-M) of a population committed to divide at its
      end. The model is structured by the time spent by a cell in the proliferative
      phase, and by the amount of Cyclin D/(CDK4 or 6) complexes. Cells can transit
      from one compartment to the other, following transition rules which differ
      according to the tissue state: healthy or tumoral. The asymptotic behaviour of
      solutions of the nonlinear model is analysed in two cases, exhibiting tissue
      homeostasis or tumour exponential growth. The model is simulated and its analytic
      predictions are confirmed numerically.

PMID- 18064466
TI  - The evolutionary conserved BER1 gene is involved in microtubule stability in
      yeast.
AB  - In yeast, microtubules are dynamic filaments necessary for spindle and nucleus
      positioning, as well as for proper chromosome segregation. We identify a function
      for the yeast gene BER1 (Benomyl REsistant 1) in microtubule stability. BER1
      belongs to an evolutionary conserved gene family whose founding member
      Sensitivity to Red light Reduced is involved in red-light perception and
      circadian rhythms in Arabidopsis. Here, we present data showing that the
      ber1Delta mutant is affected in microtubule stability, particularly in presence
      of microtubule-depolymerising drugs. The pattern of synthetic lethal interactions
      obtained with the ber1Delta mutant suggests that Ber1 may function in N-terminal
      protein acetylation. Our work thus suggests that microtubule stability might be
      regulated through this post-translational modification on yet-to-be determined
      proteins.

PMID- 18064467
TI  - DFL, a FLORICAULA/LEAFY homologue gene from Dendranthema lavandulifolium is
      expressed both in the vegetative and reproductive tissues.
AB  - FLO/LFY homologue genes were initially characterized as floral meristem identity
      genes and play a key role in flower development among diverse species. The
      inflorescence organization of chrysanthemum differs from typical dicotyledons
      such as Arabidopsis and Antirrhinum as clear sepals are absent, and instead, a
      pappus, a rudimentary sepal, is formed. To understand the mechanism of
      reproduction of chrysanthemum at the molecular level, DFL, a FLORICAULA/LEAFY
      homologous gene, was cloned from Dendranthema lavandulifolium, which is one of
      the original species of chrysanthemum. The DFL gene consists of a 1,236-bp open
      reading frame and encodes a putative protein of 412 amino acids, which is 63%
      identical to LFY and 70% to FLO. The expression patterns of DFL during the flower
      development were analyzed, and RT-PCR results showed that DFL was strongly
      expressed in the flower bud. In situ hybridization experiments showed that it is
      strongly expressed in the inflorescence bract, petal and stamen primordial
      tissues throughout the inflorescence development. Its expression signals were
      also detected in stems, leaf primordial tissues and developing inflorescence
      bracts.

PMID- 18064468
TI  - Pinching forces in crayfish and fiddler crabs, and comparisons with the closing
      forces of other animals.
AB  - The pinching forces of crustaceans are in many respects analogous to the biting
      forces of vertebrates. We examined the effects of body size and chelae size and
      shape, on the closing forces of the fiddler crab, Uca pugilator, and the
      crayfish, Procambarus clarkii. We hypothesized that the allometric relationships
      would be similar among species, and comparable to those reported for other
      decapod crustaceans. We further hypothesized that the scaling of the closing
      forces of crustaceans, with respect to body size and with the geometry of the
      pinching or biting structures, would be similar to that of vertebrates. We found
      that pinching forces increased with body mass, claw dimensions, and claw mass in
      U. pugilator, but only with claw height and claw mass in P. clarkii. Contraction
      time increased with body mass for both species combined, whereas contraction
      speed decreased. Pooled data for these and 17 other species of decapod crustacean
      revealed a positive correlation between the pinching force and body mass with a
      scaling exponent of 0.71. These data are remarkably comparable to the values on
      closing forces of vertebrate jaws, with the pooled data having a scaling exponent
      of 0.58, slightly below the value of 0.67 predicted for geometric similarity.
      Maximum closing forces vary tremendously among both crustaceans and animals in
      general, with body size and food habits being among the most important
      determining factors.

PMID- 18064469
TI  - Costs of diving by wing and foot propulsion in a sea duck, the white-winged
      scoter.
AB  - Most birds swim underwater by either feet alone or wings alone, but some sea
      ducks often use both. For white-winged scoters (Melanitta fusca), we measured
      costs (V(O2)) of dives to 2 m with descent by feet only versus wings + feet (only
      feet are used at the bottom). Dive costs repaid during the recovery period after
      a dive bout were an important fraction (27-44%) of total dive costs, and removing
      costs of extraneous surface behaviors increased resolution of differences between
      dive types. Scoters using wings + feet had 13% shorter descent duration, 18%
      faster descent speed, 31% fewer strokes/m, and 59% longer bottom duration than
      with feet only. The cost of time underwater for dives using wings + feet was 32
      37% lower than with feet only (P = 0.09 to 0.15). When indirect methods were used
      to partition descent costs from costs of ascent and bottom phases, using wings +
      feet lowered descent cost by an estimated 34%. Thus, using wings + feet increases
      descent speed and lowers descent cost, leaving more time and energy for bottom
      foraging. For birds in cold water, the large savings may result from both
      biomechanical and thermoregulatory factors.

PMID- 18064470
TI  - Postgraduate medical education in paediatric surgery: videoconferencing--a
      possible solution for Africa?
AB  - Africa faces a triple burden of disease; HIV, tuberculosis and malaria. Despite
      this, its population is expected to double over the next 45 years. There is a
      dire shortage of medical specialists and many countries lack suitably qualified
      doctors to train medical specialists. Videoconferencing offers the opportunity to
      share scarce human resources. In the South African province of KwaZulu-Natal
      there are only three paediatric surgeons who meet the clinical needs of the
      province and offer training in paediatric surgery to general surgeons in
      training. This paper reports an 18-month experience using videoconferenced
      postgraduate medical education in paediatric surgery in a South African setting.
      Seventy-one videoconference postgraduate teaching sessions of 1 h duration were
      broadcast to up to four sites in South Africa. Teaching sessions were in a
      lecture format with discussion thereafter. On average, 18 people at receive sites
      took part in each session in 2005 and 37 in 2006. There was universal
      satisfaction with videoconferenced teaching from those teaching and the
      participants at the distant sites. There is a demand to extend this project to
      other parts of South Africa and into Africa, where the shortage of paediatric
      surgeons is acute.

PMID- 18064472
TI  - Synchronous adenocarcinoma of the lung and neuroendocrine carcinoma of the ileum.

PMID- 18064471
TI  - Adjuvant and neoadjuvant chemoradiation or radiotherapy in rectal cancer--a
      review focusing on open questions.
AB  - BACKGROUND: The therapy of rectal cancer has been a matter of debate since
      decades, especially with regard to the benefits of neoadjuvant or adjuvant
      therapies. Principles of additional therapies have been established nearly two
      decades ago and are questioned nowadays on the basis of more recently modified
      operative techniques. Benefits and sequelae of therapies have to be balanced
      against each other, and it seems somewhat likely that a more differentiated
      strategy than simply stating that every patient with stage II and III rectal
      cancer needs chemoradiation or radiotherapy will, in long term, be recommended.
      CONCLUSION: It should be kept in mind that results of centers of excellence and
      of phase-III studies with their positively selected patient populations are not
      representative for all the patients with rectal cancer and physicians treating
      them.

PMID- 18064474
TI  - A COX-2 inhibitor combined with chemoradiation of locally advanced rectal cancer:
      a phase II trial.
AB  - BACKGROUND AND AIM: The aim of this study was to investigate the possible effect
      of a COX-2 inhibitor in addition to chemoradiation of locally advanced rectal
      cancer. MATERIALS AND METHODS: The study included 35 patients with rectal
      adenocarcinoma. All patients had a tumor localised <or=10 cm from the anal verge
      and a circumferential margin <or=5 mm on a magnetic resonance scan. The patients
      were scheduled to receive external radiation with a tumor dose of 60 Gy
      supplemented with an endorectal boost of 5 Gy. Concurrent with radiation, the
      patients received uracil-tegafur 300 mg/m(2) daily. Celexocib was scheduled
      throughout the radiation period in a dose of 400 mg x 2 daily. RESULTS: A macular
      papular rash was seen in 17 (49%) of the patients leading to stop of medication
      with celecoxib. Thirty-three patients were operated, and all patients responded
      to treatment. Complete pathological remission was found in 21% of the patients
      and further 24% had only microscopic residual tumor cells. The results did not
      suggest any difference according to the accomplishment of the COX-2 medication.
      CONCLUSION: The addition of a COX-2 inhibitor to chemotherapy-enhanced radiation
      treatment of rectal cancer was not feasible due to a high incidence of rash in
      the present study.

PMID- 18064473
TI  - Radical surgery for early colorectal cancer--anachronism or oncologic necessity?
AB  - BACKGROUND AND AIMS: Because of their low morbidity and mortality, limited
      resection or local excision are accepted therapeutical approaches in early
      colorectal cancer treatment. Even though, recent publications report recurrence
      rates after local excision of rectal cancer in up to 30%. This prompted us to
      evaluate our data for T1N0 colorectal cancer treated by radical surgery regarding
      recurrence, morbidity, mortality, and survival rates. MATERIALS AND METHODS:
      Clinical, histopathological, and surveillance data from our prospective
      "colorectal cancer database" from 1979 to 2005 were analyzed to evaluate outcome
      and prognosis of T1N0 colorectal cancer treated by radical surgery. Only curative
      resections were included in this study. All patients were followed in an internal
      surveillance program, which enabled us to prospectively assess morbidity,
      mortality, and survival. RESULTS A total of 105 T1N0 colon and 69 rectal
      carcinomas were included in the study. Overall morbidity was 25% (colon) and 34%
      (rectum). Thirty-day mortality was 1.9% (colon) and 4.3% (rectum). After a median
      follow-up of 92 and 87 month, no isolated local recurrence occurred. One patient
      developed both local recurrence and liver metastases. Distant metastases were
      seen in 4.9% (colon) and 7.5% (rectum). The 5- and 10-year overall survival was
      86 and 71% (colon) and 82 and 68% (rectum), respectively. CONCLUSION: Even if
      radical surgical approaches are associated with a higher rate of morbidity and
      mortality, our data show that radical surgery for T1N0 colorectal cancer results
      in excellent tumor control which is of paramount importance for the patients'
      prognosis and survival. Combining the data presented with those of the current
      literature suggests that local approaches to rectal cancer can be recommended for
      highly selected T1N0 tumors, in palliative situations, or if the patient is unfit
      for general surgery.

PMID- 18064475
TI  - Inflammatory mediators in diabetic and non-diabetic lumbosacral radiculoplexus
      neuropathy.
AB  - Nerve microvasculitis and ischemic injury appear to be the primary and important
      pathogenic alterations in lumbosacral radiculoplexus neuropathy of patients with
      (DLRPN) and without (LRPN) diabetes mellitus (DM). Here, we examine the
      involvement of inflammatory mediators in DLRPN and LRPN. Paraffin sections of
      sural nerves from 19 patients with DLRPN, 13 patients with LRPN, and 20 disease
      control patients were immunostained for intercellular adhesion molecule-1 (ICAM
      1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nuclear
      factor kappaB (NF-kappaB). The findings were correlated with histopathology. The
      pathologic and immunohistochemical alterations of DLRPN and LRPN nerves were
      indistinguishable. The nerves of both types of LRPN had a significantly greater
      number of ICAM-1 positive vessels than did the controls (P < 0.01). TNF-alpha
      expression was seen in Schwann cells and some macrophages of DLRPN and LRPN
      nerves, whereas IL-6 expression was minimal. There was greater NF-kappaB
      immunoreactivity in vessels and endoneurial cells of DLRPN and LRPN nerves than
      of the controls (P < 0.001). NF-kappaB expression correlated with the number of
      empty nerve strands (P < 0.01) and the frequency of axonal degeneration (P <
      0.05), whereas TNF-alpha expression correlated inversely with the number of empty
      nerve strands of teased fibers (P < 0.05). Our findings suggest that up
      regulation of inflammatory mediators target different cells at different disease
      stages and that these mediators may be sequentially involved in an immune
      mediated inflammatory process that is shared by both DLRPN and LRPN. Up-regulated
      inflammatory mediators may be immunotherapeutic targets in these two conditions.

PMID- 18064476
TI  - The extent of laceration of circumferential fibers with suture repair of the knee
      meniscus. Winner of the AGA DonJoy award 2006.
AB  - INTRODUCTION: Cannulas used with suture based meniscal repair techniques can
      potentially injure the load transmitting fibers of the meniscus. The subject of
      this study was to quantify this effect in a porcine in vitro model. MATERIALS AND
      METHODS: From fresh frozen medial porcine menisci tissue specimens were harvested
      following the course of the peripheral circumferential fibers bundles. In the
      first part of the study the tissue samples were perforated with the cannulas of
      either a Fast Fix or a Rapidloc device or with an 18-gauge needle. The specimens
      were then visually inspected for fiber damage using low power microscopy and the
      mean size of the laceration was measured. Finally, the extent of the tissue
      laceration was indirectly determined using non-contact strain measurements of the
      samples before and after puncture. RESULTS: When advanced with the cutting edge
      perpendicular to the fibers, the cannulas consistently cut the fibers while those
      were rather separated with the opposite orientation. It could be shown that
      specimens with a mean width of 8.1 mm lost 25% of the load transmitting cross
      section when being perforated two times with a Fast Fix device (P < 0.001). This
      effect is negated when the cannula was oriented in line with the fibers.
      CONCLUSIONS: Cannulas used for suture based meniscal repair can cause a
      substantial laceration of the meniscal tissue. The effect strongly depends on the
      orientation of the cutting edge of the cannula relative to the course of the
      fibers and can thus potentially be avoided by an appropriate handling and design.

PMID- 18064477
TI  - The fate of osteochondral grafts after autologous osteochondral transplantation:
      a one-year follow-up study in a minipig model.
AB  - INTRODUCTION: Because articular cartilage shows little intrinsic capacity of
      spontaneous regeneration, a variety of treatment options are currently at use to
      repair cartilage damage. One of these is the autologous osteochondral
      transplantation (AOT). The aim of the present work was to study the histological
      changes during the progress of 1 year after AOT in the knee joint. MATERIALS AND
      METHODS: Twelve Minipigs underwent an AOT on the medial femoral condyles of both
      knees using cooled diamond studded trephines with a diameter of the grafts of 4.6
      mm. Three animals were sacrificed at each 2, 8, 26 and 52 weeks after the
      operation. The condyles were analyzed histologically and immunohistologically for
      collagen types I and II. RESULTS: A successful bony incorporation was observed in
      all specimens. The transplant demonstrated an increasingly stable integration of
      the chondral matrix into the cartilage of the surrounding femoral condyle. At 52
      weeks after the operations 5 of 6 condyles showed a chondral integration at least
      at one side of the graft. Immunohistologically all specimens showed physiological
      staining characteristics up to 52 weeks after operation. The quality of the
      chondral part of the graft showed a wide range of variations, ranging from vital
      tissue resembling native cartilage after 52 weeks, to severe degenerative signs
      beginning 2 weeks after operation and ending at 52 weeks with deep fissures
      fragmenting the cartilage and the complete loss of vital cells. CONCLUSION: The
      press-fit technique allows a stable bony incorporation. A chondral integration of
      the graft seems to occur, provided that a close contact between the interfaces
      can be achieved. Present results demonstrate a vital cartilagenous transplant for
      up to 52 weeks. However, some specimens showed in part severe degenerative signs.
      A possible explanation is an insufficient cooling of the trephines in relation to
      the small diameter of the grafts used in the minipig model. The collagen network
      seems not to be affected for up to 52 weeks.

PMID- 18064478
TI  - Relationship between expression of tight junction-related molecules and perturbed
      epidermal barrier function in UVB-irradiated hairless mice.
AB  - In epithelia, tight junctions (TJs) create a primary barrier to the diffusion of
      solutes through the paracellular pathway. Although TJ-related molecules are
      present in the epidermis, the precise mechanisms underlying TJ functions in this
      tissue remain unclear. In this study, we use an ultraviolet (UV) B-irradiated
      murine skin model, in which the epidermal barrier function has been perturbed, to
      demonstrate a correlation between the expression patterns of TJ-related molecules
      and the epidermal permeability of TJs. Occludin remained localized in the upper
      epidermis, regardless of UVB irradiation (0.15 J per cm(2)). ZO-1 was localized
      in the upper portion of normal epidermis, and within 3-4 days of UVB irradiation,
      it was expressed throughout the upper epidermis and their expression coincided
      with epidermal thickening. Protein expression of claudin-1 and occludin did not
      alter until 3 and 4 days after UVB irradiation, respectively and thereafter
      expression remained elevated above pre-irradiation levels. An in vivo epidermal
      permeability assay revealed that tight junction-barrier function was perturbed by
      UVB irradiation, whereby biotinylated markers clearly permeated the stratum
      granulosum 3-5 days after irradiation. These results suggest that TJ-related
      molecules play important roles in epidermal barrier function in murine skin and
      show that changes in their expression patterns are associated with epidermal
      barrier perturbation after UVB irradiation. Specifically, it appears that
      epidermal barrier recovery is accelerated by the increased production and dense
      localization of occludin in the cell-cell contact region of the stratum
      granulosum.

PMID- 18064479
TI  - Outcome of surgical management of persistent or recurrent neck mass in patients
      with nasopharyngeal carcinoma after radiotherapy.
AB  - Nasopharyngeal carcinoma (NPC) patients may have persistent or recurrent neck
      masses following radiotherapy. The clinicopathological features for these two
      subgroups are not fully characterized, however. In this study, we reviewed our
      experiences in patients with neck masses underwent either local excision or neck
      dissection. Between 1990 and 2004, 37 NPC patients who had persistent (n=18) or
      recurrent (n=19) neck masses following radiotherapy were enrolled. The clinical
      and pathological parameters were measured. Squamous cell carcinoma was found in
      the resected specimens of 72.2% of the patients (13/18) with persistent neck mass
      and 89.5% of the analogs with the recurrent form (17/19). Extra-nodal tumor
      extension was noted in 53.8% (7/13) of persistent neck malignancies and 64.7%
      (11/17) of the recurrent variants. At the time of the neck surgery, individuals
      with persistent neck malignancies had fewer concomitant distant failures (23.1%,
      3/13) as compared to their counterparts with the recurrent form (58.8%, 10/17)
      (P=0.07). At the end of the follow-up, however, the rates of local and/or distant
      failures were both high for the persistent (92.3%, 12/13) and recurrent groups
      (76.5%, 13/17). In conclusion, following radiotherapy for NPC, both persistent
      and recurrent neck masses were associated with a high rate of squamous cell
      carcinoma. Although patients with persistent neck malignancies have significantly
      fewer additional sites of failures at the time of their neck surgeries, they tend
      to develop local and/or distant recurrences later during follow-up.

PMID- 18064480
TI  - Assessment of odor identification function in Asia using a modified "Sniffin'
      Stick" odor identification test.
AB  - Odor familiarity is an important factor for odor identification but varies
      profoundly in different areas. The "Sniffin' Stick" odor identification test
      originates from Europe. Modification should be made before it can be used to
      assess olfactory function in Asia. Replacement of some odorants with more
      familiar ones is a direct method of modification. The purpose of this study was
      to establish a modified version of the "Sniffin' Stick" odor identification test.
      Five odors of the original odor identification test were changed to become the
      Veterans-General-Hospital (VGH) version "Sniffin' Stick" odor identification
      test. The identifiability, intensity and hedonic tone of the odors were
      characterized. One hundred and thirty-five subjects with subjectively normal
      olfaction were enrolled to test the VGH-version set. Another 37 subjects with
      subjectively normal olfaction were enrolled to investigate the correlation
      between the original and VGH-version test. The characteristics of odorants in the
      VGH-version odor identification test fulfilled the prerequisite of the "Sniffin'
      Stick" odor identification test. The age effect on the olfactory function was
      clearly present in the VGH-version test. The test-retest correlation coefficient
      was 0.85. The tenth percentile of the VGH-version was 14, which served as an
      absolute cut-off value of normosmia. The Pearson correlation coefficient of the
      two sets of "Sniffin' Stick" odor identification was r = 0.72. The VGH-version of
      the "Sniffin' Stick" odor identification test is well characterized and capable
      of assessment of odor identification in the Asian region.

PMID- 18064481
TI  - Codeine accumulation and elimination in larvae, pupae, and imago of the blowfly
      Lucilia sericata and effects on its development.
AB  - The aim of this study was to evaluate the reliability of insect larvae as samples
      for toxicological investigations. For this purpose, larvae of Lucilia sericata
      were reared on samples of minced pig liver treated with different concentrations
      of codeine: therapeutic, toxic, and potentially lethal doses. Codeine was
      detected in all tested larvae, confirming the reliability of these specimens for
      qualitative toxicology analysis. Furthermore, concentrations measured in larvae
      were correlated with levels in liver tissue. These observations bring new
      elements regarding the potential use of opiates concentrations in larvae for
      estimation of drug levels in human tissues. Morphine and norcodeine, two codeine
      metabolites, have been also detected at different concentrations depending on the
      concentration of codeine in pig liver and depending on the substance itself. The
      effects of codeine on the development of L. sericata were also investigated.
      Results showed that a 29-h interval bias on the evaluation of the larval stage
      duration calculated from the larvae weight has to be considered if codeine was
      present in the larvae substrate. Similarly, a 21-h interval bias on the total
      duration of development, from egg to imago, has to be considered if codeine was
      present in the larvae substrate.

PMID- 18064482
TI  - Hypophyseal corticosteroids stimulate somatotrope differentiation in the
      embryonic chicken pituitary gland.
AB  - Although it is known that glucocorticoids induce differentiation of growth
      hormone (GH)-producing cells in rodents and birds, the effect of
      mineralocorticoids on GH mRNA expression and the origin of corticosteroids
      affecting somatotrope differentiation have not been elucidated. In this study, we
      therefore carried out experiments to determine the effect of mineralocorticoids
      on GH mRNA expression in the chicken anterior pituitary gland in vitro and to
      determine whether corticosteroids are synthesized in the chicken embryonic
      pituitary gland. In a pituitary culture experiment with E11 embryos, both
      corticosterone and aldosterone stimulated GH mRNA expression and increased the
      number of GH cells in both lobes of the pituitary gland in a dose-dependent
      manner. These effects of the corticosteroids were significantly reversed by
      pretreatment with mifepristone, a glucocorticoid receptor (GR) antagonist, or
      spironolactone, a mineralocorticoid receptor (MR) antagonist. Interestingly, an
      in vitro serum-free culture experiment with an E11 pituitary gland showed that
      the GH mRNA level spontaneously increased during cultivation for 2 days without
      any extra stimulation, and this increase in GH mRNA level was completely
      suppressed by metyrapone, a corticosterone-producing enzyme P450C11 inhibitor.
      Moreover, progesterone, the corticosterone precursor, also stimulated GH mRNA
      expression in the cultured chicken pituitary gland, and this effect was blocked
      by pretreatment with metyrapone. We also detected mRNA expression of enzymes of
      cytochrome P450 cholesterol side chain cleavage (P450scc) and 3beta
      hydroxysteroid dehydrogenase1 (3beta-HSD1) in the developmental chicken pituitary
      gland from E14 and E18, respectively. These results suggest that
      mineralocorticoids as well as glucocorticoids can stimulate GH mRNA expression
      and that corticosteroids generated in the embryonic pituitary gland by intrinsic
      steroidogenic enzymes stimulate somatotrope differentiation.

PMID- 18064483
TI  - Male and female upper body sweat distribution during running measured with
      technical absorbents.
AB  - Body sweat distribution over the upper body in nine clothed male and female
      runners of equal fitness while running at 65% VO(2max) and subsequent 15-min rest
      in a moderate climate (25 degrees C, 53% rh) was investigated using technical
      absorbent materials to collect the sweat produced. No significant difference in
      whole body mass loss (male 474 SD 80; female 420 SD 114 g m(-2) h(-1)) nor
      surface weighted average of all tested zones for exercise (male 636 SD 165;
      female 565 SD 222 g m(-2) h(-1)) nor rest (male 159 SD 46; female 212 SD 75 g m(
      2) h(-1)) were observed. Local sweat rate (LSR) ranges were large and overlapped
      substantially in most areas. Males showed higher LSR for the mid-front (P <
      0.05), sides (P < 0.05), and mid lateral back (P < 0.01) compare to females. Both
      sexes showed similar sweat distribution patterns over the upper body with some
      exceptions. Males showed higher relative (local to overall) sweat rates than
      females for the mid lateral back (P < 0.001), while it was lower for the upper
      arm (P < 0.001), lateral lower back (P < 0.05), and upper central back (P <
      0.05). Sweating in both sexes was highest along the spine, and higher on the back
      as a whole than the chest as a whole. Upper arm sweat rate was lowest. Males
      showed a higher ratio of highest to lowest LSR (4.4 vs. 2.8; P < 0.05). The
      present study has provided more detailed information, based on more subjects, on
      upper body sweat distribution than previously available, which can be used in
      clothing design, thermo-physiological modelling, and thermal manikin design.

PMID- 18064484
TI  - Computational modeling of paroxysmal depolarization shifts in neurons induced by
      the glutamate release from astrocytes.
AB  - Recent experimental studies have shown that astrocytes respond to external
      stimuli with a transient increase of the intracellular calcium concentration or
      can exhibit self-sustained spontaneous activity. Both evoked and spontaneous
      astrocytic calcium oscillations are accompanied by exocytosis of glutamate caged
      in astrocytes leading to paroxysmal depolarization shifts (PDS) in neighboring
      neurons. Here, we present a simple mathematical model of the interaction between
      astrocytes and neurons that is able to numerically reproduce the experimental
      results concerning the initiation of the PDS. The timing of glutamate release
      from the astrocyte is studied by means of a combined modeling of a vesicle cycle
      and the dynamics of SNARE-proteins. The neuronal slow inward currents (SICs),
      induced by the astrocytic glutamate and leading to PDS, are modeled via the
      activation of presynaptic glutamate receptors. The dependence of the
      bidirectional communication between neurons and astrocytes on the concentration
      of glutamate transporters is analyzed, as well. Our numerical results are in line
      with experimental findings showing that astrocyte can induce synchronous PDSs in
      neighboring neurons, resulting in a transient synchronous spiking activity.

PMID- 18064485
TI  - Serum levels of interleukin-1 receptor antagonist (IL-1ra) in thyroid cancer
      patients.
AB  - BACKGROUND AND AIMS: There is growing evidence that cytokines and their
      antagonists are important in the pathogenesis of various malignancies. While
      there are several reports on interleukin-1 receptor antagonist (IL-1ra) gene
      polymorphism and tissue expression, there is only little data available on the
      impact of IL-1ra serum levels. Therefore, we performed a prospective study,
      analyzing IL-1ra in thyroid cancer patients. MATERIALS AND METHODS: We measured
      preoperative IL-1ra serum levels of 52 consecutive patients with thyroid cancer,
      15 with benign adenoma and 27 healthy volunteers. The final histological
      diagnosis revealed 21 patients with papillary and 8 patients with follicular
      carcinoma (FTC), while 12 cases of medullary and 11 cases of anaplastic carcinoma
      (ATC) were observed. RESULTS: Compared to the control group, serum concentrations
      of IL-1ra were significantly higher in ATC and FTC patients. Concerning gender
      differences, this effect reached significance only in women with ATC and FTC.
      Except for the stage IV disease in ATC, there was no correlation between IL-1ra
      levels and International Union Against Cancer staging. CONCLUSION: The findings
      of our study indicate that IL-1ra may play an important role in the development
      of ATC and FTC. Future efforts should focus on the possible application of IL-1ra
      as a biomarker for the above-mentioned thyroid malignancies.

PMID- 18064486
TI  - Is IDO a key enzyme bridging the gap between tumor escape and tolerance
      induction?
AB  - BACKGROUND: Shaping immune responses to prevent tumor-induced tolerance or
      transplant rejection after solid organ transplantation is a permanently expanding
      field of research. Immunological tolerance, in this case, is a double-edged
      sword. Tumors escape immune surveillance by creating an abnormal state of
      tolerance towards their own antigens, whereas transplantation medicine is
      challenged to develop new strategies to induce allograft-specific immunological
      tolerance. One mechanism possibly capable of achieving immunoregulation is based
      on indoleamine-2,3-dioxygenase (IDO). OBJECTIVE: This overview article focuses on
      IDO-mediated tryptophan catabolism with special regard to its role in cancer and
      transplantation immunology. RESULTS: The historical view about IDO as a host's
      antimicrobial defence mechanism has been extended by the observation that its
      expression is essential for successful allogeneic pregnancy. Subsequent studies
      analysing IDO as an immune-regulatory enzyme describe its implications in cancer
      immune escape, as chemical abrogation of enzyme activity with 1-methyl-tryptophan
      (1-MT), results in enhanced antitumor responses in animal models. Therefore, a
      clinical trial treating cancer patients with 1-MT has been started. IDO also
      seems to play an essential role in the control of allo- and autoreactive T cell
      responses. CTLA4-Ig is able to induce IDO expression in dendritic cells (DCs) and
      consequently renders them tolerogenic, which might provide one explanation for
      the observed therapeutic effects of abatacept and belatacept. CONCLUSION: There
      is evidence that IDO achieves immune modulation in several animal models.
      However, in humans, this remains controversially discussed.

PMID- 18064487
TI  - An historical perspective on cell mechanics.
AB  - The physical properties of the protoplasm have long been of interest, and today,
      several intricate methods, including atomic force microscopy, have been employed
      in studies of cellular mechanics. However, many current concepts and experimental
      approaches actually have their beginnings over 300 years ago. Unfortunately,
      these pioneering studies have been all but forgotten. In this paper, we have
      reviewed some of the early literature on cellular mechanics to place modern work
      within an historical framework. It is clear that with current nanoscience
      approaches, modern experiments employing cell indentation, manipulation, particle
      rheology and micro- or nano-needle poking are now quantifying mechanical
      properties which were only qualitatively described 100 years ago. Aside from the
      variety of approaches our predecessors have employed to understand cellular
      mechanics, we feel an understanding of the past will help to propel nanoscience
      into the future. As nanophysiology and nanomedicine are developing, we as a
      community should take time to consider the early roots of these fields.

PMID- 18064489
TI  - Targeting c-KIT, PDGFR in cancer of unknown primary: a screening study for
      molecular markers of benefit.
AB  - AIMS: In view of available targeted therapies, we investigated the presence of c
      kit, PDGFR gene mutations and protein expression in cancer of unknown primary
      (CUP) in order to study their contribution in pathogenesis, their prognostic
      value and potential as therapeutic targets. METHODS: Mutations in hot spots c-kit
      exon 11 and PDGFR exons 12 and 18 were studied in paraffin-embedded tumour
      samples from 50 patients with CUP by means of PCR-based single-strand
      conformational polymorphism and protein expression by means of streptavidin
      biotin immunoperoxidase assays. Molecular markers were screened for possible
      correlations with patient outcome. RESULTS: No shifted band was detected in any
      of the polyacrylamide gel electrophoreses, indicating absence of c-kit exon 11
      and PDGFR exon 12, 18 mutations. Immunohistochemical analysis in 37 tumours
      revealed positive membranous CD117 expression in 30 samples (81%) of which five
      exhibited strong (+3), four moderate (+2) and 21 weak (+1) staining. PDGFRa
      protein staining was seen in 15 out of 30 (50%) cases, mostly weak (13) and
      rarely moderate (1) or strong (1). The expression of KIT or PDGFRa protein did
      not correlate with the clinical outcome of the patients in our cohort.
      CONCLUSIONS: In a moderate-sized CUP patient cohort, KIT or PDGFRa protein
      overexpression is rare, does not have gross prognostic significance for survival
      and is not associated with presence of activating mutations.

PMID- 18064488
TI  - Expression of rice heat stress transcription factor OsHsfA2e enhances tolerance
      to environmental stresses in transgenic Arabidopsis.
AB  - Plant growth and crop yields are limited by high-temperature stresses. In this
      study, we attempted to isolate the rice genes responsible for high-temperature
      stress tolerance using a transformed Arabidopsis population expressing a full
      length cDNA library of rice. From approximately 20,000 lines of transgenic
      Arabidopsis, we isolated a thermotolerant line, R04333, that could survive
      transient heat stress at the cotyledon stage. The rice cDNA inserted in R04333
      encodes OsHsfA2e, a member of the heat stress transcription factors. The
      thermotolerant phenotype was observed in newly constructed transgenic Arabidopsis
      plants expressing OsHsfA2e. Among 5 A2-type HSF genes encoded in the rice genome,
      four genes, including OsHsfA2e, are induced by high temperatures in rice
      seedlings. The OsHsfA2e protein was localized to the nuclear region and exhibited
      transcription activation activity in the C-terminal region. Microarray analysis
      demonstrated that under unstressed conditions transgenic Arabidopsis
      overexpressing OsHsfA2e highly expressed certain stress-associated genes,
      including several classes of heat-shock proteins. The thermotolerant phenotype
      was observed not only in the cotyledons but also in rosette leaves, inflorescence
      stems and seeds. In addition, transgenic Arabidopsis exhibited tolerance to high
      salinity stress. These observations suggest that the OsHsfA2e may be useful in
      molecular breeding designed to improve the environmental stress tolerance of
      crops.

PMID- 18064490
TI  - Predominance of subtype 3 among Blastocystis isolates from a major hospital in
      Singapore.
AB  - Blastocystis is an enteric protozoan parasite commonly found in humans and
      animals. Phylogenetic and genotypic analyses have shown that Blastocystis
      exhibits extreme genetic diversity, and humans are host to a number of zoonotic
      isolates. In the present study, the prevalence of Blastocystis in 276 stool
      samples from a hospital in Singapore was examined, and for the first time,
      riboprinting using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) was used to determine the genetic diversity of the
      Blastocystis isolated from the Singapore population. The prevalence rate was
      determined to be 3.3% (9/276), and Blastocystis displaying two main ribotypes
      were isolated. As a comparison, we performed PCR-RFLP using two different
      published methodologies, and both methods allowed the isolates to be divided into
      two distinct groups based on their riboprint patterns. According to a recently
      proposed classification scheme, 78% (7/9) of the isolates were of subtype 3,
      while 22% (2/9) were subtype 1. The predominance of subtype 3 in an urbanized
      city state such as Singapore is in agreement with the idea that subtype 3 is a
      genotype of human origin.

PMID- 18064491
TI  - Molecular cloning, purification and characterisation of myosin of human lymphatic
      filarial parasite Brugia malayi.
AB  - Global efforts have been made towards development of vaccine for prevention of
      lymphatic filariasis. However, lack of thorough knowledge about developmental
      biology and pathogenesis of filarial parasite restricts us from developing an
      effective vaccine. A limited number of immunodominant antigens of human lymphatic
      filariid Brugia malayi have been characterised; however, none of these
      recombinant antigens so far induced significant degree of protective immunity to
      challenge infection. In the present study, we identified a approximately 2.0 Kb
      cDNA clone by immunoscreening of cDNA library of adult female Brugia malayi. The
      nucleotide sequence of the identified clone showed 94.3% homology with C-terminal
      part of myosin heavy chain gene of Brugia malayi. This cDNA insert was sub-cloned
      into pET28b vector and expressed in BL21(DE3). The recombinant protein was
      purified to near homogeneity by immobilised metal affinity chromatography (IMAC)
      with yield of approximately 25 mg/l. The purified protein was recognised in
      western blot with anti-His tag antibody as also with the antibodies present in
      the sera of human W. bancrofti patients of all categories and infected/immunized
      rodent serum demonstrating its functional role. Recombinant myosin induced marked
      cellular immune response as observed by lymphoproliferation assay. The present
      findings demonstrate the usefulness of B. malayi recombinant myosin as vaccine
      candidate against human lymphatic filariasis.

PMID- 18064492
TI  - Ecological stoichiometry of indirect grazer effects on periphyton nutrient
      content.
AB  - Ecological stoichiometry has been successful in enhancing our understanding of
      trophic interactions between consumer and prey species. Consumer and prey
      dynamics have been shown to depend on the nutrient composition of the prey
      relative to the nutrient demand of the consumer. Since most experiments on this
      topic used a single consumer species, little is known about the validity of
      stoichiometric constraints on trophic interactions across consumers and
      ecosystems. We conducted a quantitative meta-analysis on grazer-periphyton
      experiments to test (1) if benthic grazers have consistent effects on the
      nutrient composition of their prey, and (2) whether these effects can be aligned
      to the nutrient stoichiometry of grazer and periphyton, other environmental
      factors, or experimental constraints. Grazers significantly lowered periphyton
      C:N and C:P ratios, indicating higher N- and P-content of grazed periphyton
      across studies. Grazer presence on average increased periphyton N:P ratios, but
      across studies the effect size did not differ significantly from zero. The sign
      and strength of grazer effects on periphyton nutrient ratios was strongly
      dependent on the nutrient content of grazers and their food, but also on grazer
      biomass, the amount of biomass removal and water column nutrients. Grazer with
      low P-content tended to reduce periphyton P-content, whereas grazers with high P
      content increased periphyton P-content. This result suggests that low grazer P
      content can be an indication of physiological P-limitation rather than a result
      of having relatively low and fixed P-requirements. At the across-system scale of
      this meta-analysis, predictions from stoichiometric theory are corroborated, but
      the plasticity of the consumer nutrient composition has to be acknowledged.

PMID- 18064493
TI  - Explaining variation in tropical plant community composition: influence of
      environmental and spatial data quality.
AB  - The degree to which variation in plant community composition (beta-diversity) is
      predictable from environmental variation, relative to other spatial processes, is
      of considerable current interest. We addressed this question in Costa Rican rain
      forest pteridophytes (1,045 plots, 127 species). We also tested the effect of
      data quality on the results, which has largely been overlooked in earlier
      studies. To do so, we compared two alternative spatial models [polynomial vs.
      principal coordinates of neighbour matrices (PCNM)] and ten alternative
      environmental models (all available environmental variables vs. four subsets, and
      including their polynomials vs. not). Of the environmental data types, soil
      chemistry contributed most to explaining pteridophyte community variation,
      followed in decreasing order of contribution by topography, soil type and forest
      structure. Environmentally explained variation increased moderately when
      polynomials of the environmental variables were included. Spatially explained
      variation increased substantially when the multi-scale PCNM spatial model was
      used instead of the traditional, broad-scale polynomial spatial model. The best
      model combination (PCNM spatial model and full environmental model including
      polynomials) explained 32% of pteridophyte community variation, after correcting
      for the number of sampling sites and explanatory variables. Overall evidence for
      environmental control of beta-diversity was strong, and the main floristic
      gradients detected were correlated with environmental variation at all scales
      encompassed by the study (c. 100-2,000 m). Depending on model choice, however,
      total explained variation differed more than fourfold, and the apparent relative
      importance of space and environment could be reversed. Therefore, we advocate a
      broader recognition of the impacts that data quality has on analysis results. A
      general understanding of the relative contributions of spatial and environmental
      processes to species distributions and beta-diversity requires that
      methodological artefacts are separated from real ecological differences.

PMID- 18064494
TI  - Differential regulation of pathogens: the role of habitat disturbance in
      predicting prevalence of Sin Nombre virus.
AB  - Deer mice (Peromyscus maniculatus) are the primary reservoir for Sin Nombre virus
      (SNV), a North American hantavirus that causes disease with high mortality in
      humans. Recent studies have proposed that habitat disturbance affects prevalence
      of SNV in deer mice; however, the outcomes proposed in these studies are in
      opposition to each other. Our objectives were to test these divergent hypotheses
      by: (1) measuring SNV infection in deer mice within a patchwork of disturbance;
      and (2) evaluating the relationships between SNV prevalence, population density
      and demography as possible mechanisms. In 2003 and 2004, we sampled 1,297 deer
      mice from 17 sites with varying levels of disturbance in the Great Basin Desert.
      Across sites and years, SNV prevalence varied from 0.0 to 38.9%. We found a
      negative relationship between SNV prevalence and disturbance. Although we found
      no direct relationship between SNV prevalence and deer mouse density, we found
      that density was highest on sites with the lowest levels of disturbance. The
      number of deer mice that survived across seasons (e.g., trans-seasonal survivors)
      differed across levels of disturbance and was greatest on our least disturbed
      study sites [Formula: see text] moderate on sites with intermediate levels of
      disturbance (x = 5.61%) and zero on highly disturbed sites. On low-disturbance
      sites, a greater proportion of trans-seasonal survivors were SNV seropositive
      (28.80%) compared to the intermediate-disturbance sites (16.67). Collectively,
      our results indicate that habitat disturbance plays a predictive role in SNV
      prevalence, with highly disturbed sites having reduced long-term survival of deer
      mice, including survival of infected individuals.

PMID- 18064495
TI  - Influence of N-acetylcysteine on renal toxicity of cadmium in rats.
AB  - The aim of this study was to investigate the ability of N-acetylcysteine (NAC) to
      prevent cadmium (Cd)-induced renal damage and whether NAC would reverse cadmium
      damage to the kidney. Fifty adult male rats were divided into five experimental
      groups: group 1 received tap water for 3 months and 7 days, group 2 received
      cadmium chloride (CdCl(2)) for 3 months, group 3 (NAC cotreatment group) received
      CdCl(2) and 0.5% NAC in tap water for 3 months, group 4 received CdCl(2) in tap
      water for 3 months and 3 months later received only tap water for 7 days, and
      group 5 (NAC posttreatment group) received CdCl(2) in tap water for 3 months and
      3 months later received 2% NAC in tap water for 7 days. NAC significantly
      decreased the elevated kidney malondialdehyde levels, as a marker of lipid
      peroxidation, in both cotreatment and posttreatment modalities. Cotreatment and
      posttreatment with NAC significantly increased kidney superoxide dismutase enzyme
      activity and glutathione level but did not change kidney catalase enzyme
      activity. NAC decreased fractional excretion of sodium in posttreatment group.
      Neither Cd nor NAC affected the glomerular filtration rate (GFR). Cotreatment and
      posttreatment with NAC reduced the effects of Cd on proximal tubules. It was
      found that NAC showed these effects without changing kidney accumulation of
      cadmium. Exogenously administrated NAC might reduce toxic effects of Cd on the
      kidney without any reduction in tissue Cd level.

PMID- 18064496
TI  - Treatment of catheter-related bacteremia with tissue plasminogen activator
      antibiotic locks.
AB  - This retrospective study was completed to investigate the effectiveness of tissue
      plasminogen activator (TPA) antibiotic locks (ABL) along with systemic
      antibiotics (AB) to clear catheter-related bacteremia (CRB) in children on
      chronic hemodialysis. There were 76 CRBs in 37 children. CRBs were successfully
      cleared with AB/ABL in 63/76 (83%) cases. Ten of 76 (13%) CRBs were symptomatic
      at 48 h of treatment. These were seven polymicrobial, two gram-negative, and one
      Candida CRB. 13/76 (17%) episodes required catheter exchange, and all were wire
      guided exchanges. TPA-ABL/AB cleared gram-positive and gram-negative CRBs
      significantly better than polymicrobial CRBs (p < 0.01). The infection-free
      survival and the rate of recurrence at 45 days was not statistically different
      between the TPA-ABL/AB group and the catheter-exchange group. If CRB was
      symptomatic at 48 h of treatment, recurrence at 6 weeks was more frequent with
      persistent use of TPA-ABL/AB (p < 0.05). There were no episodes of metastatic
      infections, catheter malfunction from occlusion, or catheter breakdown during the
      course of TPA-ABL treatments. In conclusion, TPA-ABL can be safely and
      effectively used in the management of CRB, increasing the probability of catheter
      survival and preserving the vascular access site. With the exception of
      polymicrobial CRB, there is no disadvantage in using TPA-ABL/AB over catheter
      exchange, as the infection-free survival and the rate of recurrence are
      comparable.

PMID- 18064497
TI  - Polygonum viviparum mycobionts on an alpine primary successional glacier
      forefront.
AB  - Polygonum viviparum is one of the first ectomycorrhizal (EM) plant species
      colonising primary successional sites at the Rotmoos glacier forefront (Tyrolean
      Alps, Austria). On a site with soil development of about 150 years (2,400 m above
      sea level), mycobionts of P. viviparum were identified by morphotyping and fungal
      ribosomal deoxyribonucleic acid internal transcribed spacer sequencing. For
      studying seasonal dynamics and spatial heterogeneity, ectomycorrhizae were
      sampled on five plots during all seasons. P. viviparum root tips were always EM.
      In total, 18 mycobiont taxa of the following genera were identified: Cenococcum
      (1), Cortinarius (2), Helvella (1), Inocybe (3), Russula (1), Sebacina (2),
      Thelephora (2) and Tomentella (6). All were non-specific EM partners of EM
      plants. As early as 2 weeks after spring snow melt, EM were well developed, vital
      and showed high mycobiont diversity. The relative abundance of senescent root
      tips was lowest in spring and increased throughout the year, with a maximum in
      winter (frozen soil). Thus, mycobiont growth and physiological activity obviously
      start when soil is still under snow cover: We speculate that water availability
      is one important initiation factor for mycorrhizal development under snow cover,
      when temperatures still range around the freezing point. Irrespectively of the
      season, most abundant mycobionts at this primary successional site belonged to
      the genera Tomentella, Sebacina and Cenococcum, also in frozen soil. Spatial
      heterogeneity was high when considering species composition and diversity
      indices. Overall mycobionts species richness was restricted at this site,
      probably because of the limited availability of fungal partners. We regard the
      presence/absence of fungal partner and limiting abiotic impacts of the
      environment as key factors for the symbiotic status of P. viviparum.

PMID- 18064498
TI  - Evaluation of the chemical reactivity in lignin precursors using the Fukui
      function.
AB  - The hydroxycinnamyl alcohols: p-coumarol, coniferol and sinapol are considered
      the basic units and precursors of lignins models. In this work, the specific
      reactivity of these molecules was studied. We investigate their intrinsic
      chemical reactivity in terms of the Fukui function, applying the principle of
      hard and soft acids and bases (HSAB) in the framework of the density functional
      theory (DFT). Comparisons of their nucleophilic, electrophilic and free radical
      reactivity show their most probably sites to form linkages among them. It is
      found that the most reactive sites, for reactions involving free radicals, are
      the carbons at the beta-position in the p-coumarol and sinapol molecules, whilst
      the regions around the carbon-oxygen bond of the phenoxyl group are the most
      reactive in coniferol.

PMID- 18064499
TI  - Model validation for gene selection and regulation maps.
AB  - Consider the problem of investigating the structure of a set of sample points in
      a very high dimensional (Euclidean) space. This case is paradigmatic, for
      instance, in postgenomic applications. The high dimensionality and small sample
      size make statistical inference and optimization difficult problems, such that
      selecting a model or choosing a learning algorithm face the evidence that
      currently no consensus guidelines exist. Usually, the intervention of linear or
      nonlinear projection method is required to map the observations into a low
      dimensional space with the most salient data features preserved. This step
      usually involves computing statistics from the low-dimensional projected space of
      features and then inferring on the highly dimensional original structures (the
      genes). This work deals with model validation for gene selection and regulation
      dynamics. The analysis is conducted through a mix of quantitative methods and
      qualitative aspects. A regularized inference approach is employed based on
      dimensionality reduction, data denoising, and feature extraction tasks. Each task
      requires the implementation of statistics and machine learning algorithms. We
      focus on the complex problem of inferring the coregulation from the coexpression
      gene dynamics in the presence of limited biological information and time course
      perturbation experiments. In particular, both separation and interference gene
      dynamics are considered and validated to design the most coherent underlying
      transcriptional regulatory map.

PMID- 18064500
TI  - Foreword to the special issue on "theoretical, experimental, and computational
      aspects of growth and remodeling": Michael S. Sacks and John C. Criscione (guest
      editors).

PMID- 18064501
TI  - Subjective acceptance of 7 Tesla MRI for human imaging.
AB  - OBJECTIVE: One prerequisite for transferring ultra-high-field magnetic resonance
      imaging (MRI) (>3T) into clinical diagnostic workup is a low rate of side
      effects. To our knowledge, publications of subjective acceptance and willingness
      to undergo examinations at >3T are rare. We present first results from our
      research site. MATERIALS AND METHODS: Exposure to 7 T whole-body MRI of head,
      extremities, or breast was assessed in 102 subjects. They judged sources of
      discomfort (examination duration, room temperature) and physiological sensations
      (vertigo, light flashes) on a 10-point scale, differentiating between examination
      phases: table stationary or moving. For comparison, the same questionnaire was
      completed by 43 of these subjects after undergoing a 1.5 T examination. Vertigo
      was the most pronounced sensation at 7 T with 5% rating it as very unpleasant
      (none at 1.5 T). This should be compared with the fact that the lengthy exam
      duration was regarded as even more uncomfortable. Compared to 1.5 T, average
      study duration at 7 T was roughly doubled, and 7 T elicited a wider range of
      complaints. CONCLUSION: Although the number of side effects is increased at 7 T
      compared to 1.5 T, 7 T was well tolerated by the majority of subjects. Further
      data collection is necessary for better understanding of these effects.

PMID- 18064502
TI  - Independent component analysis applied to the removal of motion artifacts from
      electrocardiographic signals.
AB  - Electrocardiographic (ECG) signals are affected by several kinds of artifacts
      that may hide vital signs of interest. In this study we apply independent
      component analysis (ICA) to isolate motion artifacts. Standard or instantaneous
      ICA, which is currently the most addressed ICA model within the context of
      artifact removal, is compared to two other ICA techniques. The first technique is
      a frequency domain approach to convolutive mixture separation. The second is
      based on temporally constrained ICA, which enables the estimation of only one
      component close to a particular reference signal. Performance indexes evaluate
      ECG complex enhancement and relevant heart rate errors. Our results show that
      both convolutive and constrained ICA implementations perform better than standard
      ICA, thus opening up a new field of application for these two methods. Moreover,
      statistical analysis reveals that constrained ICA and convolutive ICA do not
      significantly differ concerning heart rate estimation, even though the latter
      overcomes the former in ECG morphology recovery.

PMID- 18064503
TI  - The potential induced in anisotropic tissue by the ultrasonically-induced Lorentz
      force.
AB  - In the presence of a magnetic field, an ultrasonic wave propagating through
      tissue will induce Lorentz forces on the ions, resulting in an electrical
      current. If the electrical conductivity is anisotropic, this current is tilted
      toward the fiber direction, causing charge to accumulate between half
      wavelengths: positive charge where the current vectors converge and negative
      where the current vectors diverge. This charge produces an electric field in the
      direction of propagation that is associated with an electrical potential, and
      this electric field causes an additional current that is also tilted by the
      anisotropy. The final result is the total current pointing perpendicular to the
      direction of propagation and a charging of the tissue every half wavelength. The
      potential has a greater magnitude than that obtained from colloidal suspensions
      or ionic solutions (ultrasonic vibration potentials) and may be used as the basis
      of a technique to image conductivity.

PMID- 18064504
TI  - [Osteitis. Infections of the locomotive system].
AB  - Infections of the locomotive system appear in many different forms such as acute
      inflammation of joints or bone following injury or surgical or chronic processes,
      often lasting for years. They demand an exact treatment plan not only to remove
      necrotic tissue but also for reconstruction of defects. A special problem is
      infection following alloplastic reconstruction of joints or spine. Multiple
      surgical procedures are required to hinder reinfection, restore function, and
      assure acceptable patient quality of life.

PMID- 18064505
TI  - [Nobel Prize in medicine. Knockout mice revolutionize genetics].

PMID- 18064507
TI  - Sirolimus eluting stent (Cypher) in patients with diabetes mellitus: results from
      the German Cypher Stent Registry.
AB  - BACKGROUND: Patients with diabetes mellitus (DM) undergoing percutaneous coronary
      intervention (PCI) are at increased risk for adverse outcomes. The use of
      sirolimus eluting stents (SES) has been shown to improve outcomes in diabetic
      patients. Since results from randomized trials were derived from selected
      patients scientific scrutiny under real world conditions is necessary. METHODS
      AND RESULTS: 1,948 patients with DM and 4,707 patients without DM were included
      in the German Cypher Registry, a post-marketing survey of use of SES in Germany.
      In >99% of entry cases a structured clinical follow-up was completed. By
      angiographic criteria severity of coronary artery disease was higher in diabetic
      patients compared to non-diabetics. However, procedural success and in-hospital
      complication rates were comparable between DM- and non-DM-patients. 6 months MACE
      rate in the DM group was significantly higher than in the non-DM group (16.4% vs.
      13.0%) but lower than expected from historical data with the use of bare metal
      stents (BMS). CONCLUSION: The results with SES in diabetics are encouraging but
      DM remains a risk factor for poor outcome of PCI. No statement is justified
      whether the treatment of diabetics with SES is at least as safe as bypass
      surgery. This intriguing question has to be answered in a direct randomized head
      to-head comparison with state of the art surgery.

PMID- 18064509
TI  - In an interesting survey, Caulfield and coauthors from the United Kingdom
      contribute to our understanding of factors that influence editors to accept or
      reject plastic surgery papers.

PMID- 18064508
TI  - Polymorphisms of human leukocyte antigen genes in korean children with Kawasaki
      disease.
AB  - BACKGROUND: Kawasaki disease is a leading cause of acquired heart disease in
      children. The prevalence rate varies in different ethnic groups. Recently, with
      the clinical application of molecular genetic technology, human leukocyte antigen
      (HLA) polymorphisms associated with several diseases have been identified by DNA
      analysis. This study aimed to assess the association of HLA alleles with
      susceptibility and complications of Kawasaki disease in Korean children. METHODS:
      In this study, DNA was extracted from 74 children with a diagnosis of Kawasaki
      disease. The polymorphisms of the HLA-A, -B, -C, and -DRB1 alleles of patients
      with Kawasaki disease were determined by polymerase chain reaction (PCR)
      amplification refractory mutation system (ARMS) and PCR-sequence-specific primer
      (SSP) analysis. The polymorphisms identified were compared with those of 159
      normal healthy control subjects. RESULTS: There was a significant increase in the
      frequencies of the HLA-B35, -B75, and -Cw09 alleles in patients with Kawasaki
      disease compared with the healthy control group. There was no increase in the
      frequency of HLA-DRB1 alleles among the Kawasaki disease patients compared with a
      healthy control group. When the patients with Kawasaki disease were divided into
      two subgroups, with or without coronary complications, the Kawasaki disease
      patients with coronary complications showed a significantly increased frequency
      of the HLA-DRB1*11 allele compared with the healthy control group and increased
      frequency of HLA-DRB1*09 in a comparison of the subgroups. CONCLUSIONS: This
      study suggests that polymorphisms in some alleles of B and C in HLA class I genes
      are associated with Kawasaki disease in Korean children.

PMID- 18064510
TI  - The safety of pedicles in breast reduction and mastopexy procedures.
AB  - Nipple necrosis is a potential complication of breast reduction and mastopexy
      procedures that can be prevented if the surgeon is acquainted with the arterial
      blood supply to the breast, particularly the nipple-areolar complex (NAC). A
      review of the latest research on this with its clinical application is given.

PMID- 18064511
TI  - Daily diurnal variation in admissions for ruptured abdominal aortic aneurysms.

PMID- 18064512
TI  - Safety of laparoscopic adrenalectomy in patients with large pheochromocytomas: a
      single institution review.
AB  - BACKGROUND: Laparoscopic adrenalectomy is the procedure of choice for small
      adrenal tumors, but some concerns have been voiced when this approach is adopted
      for larger tumors and pheochromocytomas. The aim of this study was to examine the
      results of the laparoscopic resection of large pheochromocytomas. METHODS: A
      retrospective review of adrenalectomies performed for adrenal pheochromocytomas>6
      cm in diameter. We compiled and analyzed the early operative complications,
      histologic findings, and cure rates with a minimum of 1 year of follow-up after
      surgery. RESULTS: From 1996 to 2005, a total of 445 laparoscopic adrenalectomies
      were performed in our institution using the anterolateral transperitoneal
      approach. From this series we identified 18 procedures for pheochromocytomas with
      an average diameter on imaging of 78.2 mm (range 60-130 mm). All patients were
      rendered safe with a standard departmental protocol involving calcium-channel
      blockade initiated at least 2 weeks prior to surgery. The average peak
      intraoperative blood pressure was 187 mmHg. Capsular disruption occurred in two
      cases. One patient required an intraoperative blood transfusion due to
      intraoperative blood loss. No immediate conversions to an open procedure were
      required, but one patient underwent a delayed laparotomy for hematoma formation.
      Histologically, four of the adrenal tumors displayed evidence of vascular
      invasion. Biochemical cure was achieved in all patients after a median follow-up
      of 58 months (16-122 months). CONCLUSIONS: Laparoscopic adrenalectomy appears to
      be a safe and effective approach for large pheochromocytomas when no preoperative
      or intraoperative evidence of local invasion is present.

PMID- 18064513
TI  - Proton pump inhibitors relieve and prevent symptoms related to gastric acidity
      after esophagectomy.
AB  - BACKGROUND: Denervated stomach used as an esophageal substitute after
      esophagectomy often retains or spontaneously recovers acid production. The aims
      of the present study were to assess the relationship between esophageal acid
      exposure or gastric acidity and reflux-related symptoms after esophagectomy, and
      to assess the ability of proton pump inhibitors (PPIs) to relieve
      gastroesophageal reflux-related symptoms. METHODS: Forty-four patients underwent
      esophageal and gastric 24-h pH monitoring early after esophagectomy with gastric
      reconstruction. Initially, patients with both gastric acidity and reflux symptoms
      were treated with PPIs (Treatment group), then all patients with gastric acidity,
      whether symptomatic or not, were treated (Prevention group). Reflux-related
      symptoms were correlated with esophageal acid exposure and postoperative gastric
      acidity. Gastric acidity was then correlated with serum anti-Helicobacter pylori
      immunoglobulin G (IgG) titers and preoperative endoscopic findings RESULTS:
      Sixteen patients (36.4%) reporting reflux and showing gastric acid production
      were treated with PPIs, which provided relief to 13 (81.3%). Although symptoms
      did not correlate with the esophageal acid exposure, postoperative gastric
      acidity was significantly greater among patients who were symptomatic than among
      those who were not. Overall, acid production was lower in older patients (>64
      years of age), although older patients who were H. pylori-negative and without
      chronic atrophic gastritis also showed high levels of gastric acidity.
      CONCLUSIONS: Proton pump inhibitors should be administered prophylactically early
      after esophagectomy to relieve and prevent reflux-related symptoms. Candidates
      for preventive therapy include those less than 64 years of age or older patients
      who are H. pylori-negative and without chronic atrophic gastritis.

PMID- 18064514
TI  - Parathyroidectomy for renal hyperparathyroidism in children and adolescents.
AB  - BACKGROUND: Renal hyperparathyroidism (rHPT) almost inevitably develops in
      pediatric patients with end-stage chronic kidney disease (CKD) and may require
      parathyroidectomy (PTX) despite intensified conservative therapy. Long-term
      duration of uncontrolled rHPT may result in disabling osteodystrophy and vascular
      calcifications. Only a few reports on children undergoing PTX for rHPT are
      available and mainly consist of case reports with short follow-up periods. To
      study this entity, we analyzed the course of 23 pediatic patients who underwent
      PTX for rHPT. METHODS: Twenty-three patients with a mean age of 15 years and who
      underwent PTX for rHPT between 1986 and 2006 were evaluated. Surgical indications
      and techniques, specific postoperative management, and follow-up courses are
      described. RESULTS: Preoperative mean serum (s-) calcium was 2.7+/-0.05 mmol/L
      (normal range=2.2-2.7 mmol/L); s-phosphate was 1.8+/-0.1 mmol/L (normal range=0.8
      1.6 mmol/L), and mean intact parathyroid hormone (PTH) level was 1240.1+/-160.1
      pg/ml (normal range=11-65 pg/ml). Twenty-one patients underwent initial PTX and
      two patients underwent reoperative PTX. Total PTX with parathyroid
      autotransplantation (AT) was performed in 18 patients. In three patients less
      than four parathyroid glands were identified and no AT was performed
      consecutively. Postoperatively, no complications with respect to bleeding or
      vocal cord damage were recorded. The postoperative values of s-calcium, s
      phosphate, and PTH decreased to or below normal range (s-calcium=2.0+/-0.1
      mmol/L, s-phosphate=1.2+/-0.1 mmol/L, PTH=50.1+/-11.2 pg/ml). All 15 children
      below the age of 15 years required calcium intravenously. Follow-up was obtained
      in all patients 69.6+/-11.4 months after PTX. Bone pain resolved in all
      previously symptomatic patients. S-calcium was 2.2+/-0.2 mmol/L, s-phosphate was
      1.4 +/- 0.3 mmol/L, and PTH was 90.2+/-21.5 pg/ml. No patient required repeated
      parathyroid autografting, and only one underwent an explantation of his AT six
      years after initial PTX. CONCLUSION: Total PTX with AT in pediatric patients with
      rHPT is a safe and effective procedure. It should be considered if rHPT is
      refractory to conservative treatment, in view of the risk of potentially lethal
      vascular calcifications developing in the majority of adults with childhood onset
      of CKD.

PMID- 18064515
TI  - Lateral lymph node dissection guided by preoperative and intraoperative findings
      in differentiated thyroid carcinoma.
AB  - BACKGROUND: The lateral compartment frequently demonstrates metastasis from
      thyroid carcinoma. In contrast to that for central lymph node dissection, the
      indication for lateral node dissection remains controversial. METHODS: In this
      review we evaluate the indication of lateral lymph node dissection in papillary
      and follicular carcinomas based on the findings of previous reports, including
      those from our institute. RESULTS: Lymph node metastasis and recurrence at the
      lymph node are common events in papillary carcinoma. In particular, the lymph
      node recurrence rate in patients with clinically apparent lateral node metastasis
      (N1b) is high, not only in compartments that have not been dissected but also in
      those previously dissected, even if therapeutic lateral node dissection is
      performed. For N0 or N1a papillary carcinomas, male gender, being 55 or more
      years of age, a tumor larger than 3 cm, and massive extrathyroid extension are
      independent risk factors of lymph node recurrence, and patients with tumors
      having two or more of these clinicopathologic features showed high lymph node
      recurrence rates even if they underwent prophylactic lateral node dissection. In
      follicular carcinoma, node metastasis and recurrence at the node are rare events
      but they occasionally can be observed, especially in tumors with massive
      extrathyroid extension and poor differentiation. CONCLUSION: N1b is an absolute
      indication for lateral lymph node dissection. Prophylactic lateral node
      dissection is also recommended in N0 or N1a papillary carcinoma, if the lesion
      shows two or more of the aggressive characteristics indicated above. For
      follicular carcinoma, prophylactic node dissection is not mandatory but can be an
      option for tumors demonstrating aggressive characteristics or histologic types.

PMID- 18064516
TI  - Laparoscopic cholecystectomy in cirrhotic patients with symptomatic
      cholelithiasis: a case-control study.
AB  - BACKGROUND: In this study we retrospectively evaluated a group of symptomatic
      cirrhotic (n=30) and non-cirrhotic (n=60) patients submitted to laparoscopic
      cholecystectomy (LC) in a public hospital in Brazil. METHODS: The groups were
      compared for surgical time, duration of hospitalization after surgery, period of
      permanence in the intensive care unit (ICU), use of blood derivatives, mortality
      rates, and transoperative and post-surgery complications. Other parameters, such
      as hepatic reserve capacity and presence of ascites, were also analyzed. RESULTS:
      Twenty-three (76.7%) of the patients of the cirrhosis group (CG) were classified
      as Child-Pugh A, and seven (23.3%) were Child-Pugh B. Six of them (20%) had
      ascites. Differences between the two groups included surgery time (p=0.008),
      duration of hospitalization (p=0.014), and post-surgery (p=0.000) or ambulatory
      (p=0.008) complications. The worst results were observed among Child B patients
      and in those with ascites. Blood derivatives were used in only 3.3% of the CG
      patients. No cases of conversion to laparotomy were observed among the two groups
      of patients included in this study, nor were there any deaths. CONCLUSIONS: These
      results indicate that videolaparoscopic cholecystectomy may be safely performed
      in public hospitals in Brazil, with low levels of complications, no associated
      mortality, and no need for blood derivatives.

PMID- 18064519
TI  - Large metastatic lymph node size, especially more than 2 cm: independent
      predictor of poor prognosis in node-positive gastric carcinoma.
AB  - The presence of metastatic lymph nodes (MLNs) is the most important prognostic
      factor for gastric carcinoma, with the number of MLNs thought to be predictive of
      the prognosis. However, there have been long-standing debates on how to classify
      node-positive patients into prognostic groups appropriately. Recent findings in
      patients with colon and esophageal cancer have suggested that MLN size, more than
      MLN number, is an important prognostic factor; but less is known about the impact
      of MLN size on the prognosis of patients with gastric carcinoma. We therefore
      assessed the prognostic impact of large MLNs, especially those>or=2 cm, in
      patients with gastric carcinoma. A total of 1190 patients who underwent curative
      resection for gastric carcinoma between 2001 and 2003 and had lymph node
      metastases were divided into two groups according to the size of the largest
      MLN:>or=2 cm (n=51) vs. <2 cm (n=1139). Clinicopathologic data, including tumor
      recurrence and survival, were reviewed retrospectively. The median follow-up for
      living patients was 47 months (range 30-80 months). Age, sex ratio, type of
      surgery, and histologic classification did not correlate with MLN size. The depth
      of invasion did correlate with MLN size (T1-2 vs. T3-4, p=0.045) but not with the
      number of MLNs (N stage, p=0.311). The two groups showed similar distribution of
      stage according to the UICC/AJCC TNM staging system. Disease-free survival (34%
      vs. 53%, p<0.001) and overall survival (40% vs. 63%, p=0.011) were significantly
      worse in the large MLN group. Univariate analysis with the log-rank test showed
      that MLN>or=2 cm, type of surgery, T stage, N stage, and histologic
      classification had a significant impact on overall survival. Multivariate
      analysis with the Cox proportional hazard model showed that MLN>or=2 cm was an
      independent prognostic factor (hazard ratio 1.76, p=0.006), along with T stage
      and N stage. MLN>or=2 cm is an independent additional predictor of poor prognosis
      in patients with node-positive gastric carcinoma.

PMID- 18064517
TI  - Thoracoscopic removal of mediastinal hyperfunctioning parathyroid glands:
      personal experience and review of the literature.
AB  - BACKGROUND: The presence of a mediastinal hyperfunctioning parathyroid gland is a
      rare condition that occurs in about 1% to 2% of cases. We present our experience
      with video-endoscopic parathyroidectomy and a review of the literature. METHODS:
      In seven patients (four male, three female; age 28-67 years) mediastinal
      hyperfunctioning parathyroid glands were removed by the thoracoscopic route
      (VATS). Six patients suffered from primary hyperpathyroidism and one woman from
      recurrent secondary hyperparathyroidism. Additionally, articles concerning
      endoscopic treatment of mediastinal parathyroid glands were collected from the
      medical databases. A total of 58 patients were found in the English and French
      literature. RESULTS: Neither intraoperative nor postoperative complications
      occurred in our patients. Operating time was 90 minutes (range 40-180 minutes).
      After a mean follow-up of 29+/-12 months (range 3-64), all patients are
      biochemically cured. The cases in the literature showed healing in 57 of 58
      cases. Their mean operating time was 112 minutes (range 40-240 minutes). One
      perioperative death due to myocardial infarction and a major complications rate
      of 7% are described. CONCLUSION: The thoracoscopic approach to mediastinal
      parathyroidectomy is a safe, feasible technique with a low complication rate and
      good cosmetic outcome. It should become the standard surgical access for
      mediastinal hyperfunctioning parathyroid glands.

PMID- 18064520
TI  - Transcatheter closure of bilateral multiple huge pulmonary arteriovenous
      malformations with homemade double-umbrella occluders.
AB  - A 28-year-old man underwent successful transcatheter occlusion of three huge
      pulmonary arteriovenous malformations (PAVMs) using homemade double-umbrella
      occluders and stainless steel coils. Thoracic CT with three-dimensional
      reconstruction and pulmonary angiography were used for treatment planning and
      follow-up. The diameters of the feeding vessels were 11 mm, 13 mm, and 14 mm,
      respectively. This report demonstrates the novel design and utility of the double
      umbrella occluder, an alternative tool for treatment of large PAVMs.

PMID- 18064521
TI  - Actin -related protein 3 (Arp3) is mutated in proteinuric BUF/Mna rats.
AB  - The BUF/Mna strain of rat is a model of focal and segmental glomerulosclerosis
      (FSGS) in which a quantitative trait locus (QTL) for proteinuria, Pur1, has been
      identified. The aim of the present study was to identify candidates for the Pur1
      gene. To narrow the Pur1 QTL, we performed fine QTL mapping and single nucleotide
      polymorphism (SNP) genotyping. To identify candidate genes, sequencing and gene
      expression analyses of all genes contained in the narrowed locus were conducted.
      The narrowed Pur1 region contained 25 genes. Among these genes, only the Arp3
      gene was mutated in the BUF/Mna strain; it contained a missense mutation that
      caused an (L)111(F) substitution. This leucine is conserved across species. Gene
      expression analysis failed to identify any other candidate genes for Pur1. Arp3
      mediated actin assembly abnormalities were visible in immunohistochemical and
      electron microscopic examinations of podocytes in old BUF/Mna rats. Taken
      together, these data suggest that Arp3 is a candidate for the Pur1 gene. This
      observation is consistent with our growing recognition that abnormal signaling
      induced assembly of actin in podocytes leads to the development of FSGS.

PMID- 18064522
TI  - Pulmonary and mediastinal bronchogenic cysts: a clinicopathologic study of 33
      cases.
AB  - Bronchogenic cysts are uncommon congenital anomalies of foregut origin and
      usually located within the mediastinum and the lung. A retrospective study of 33
      thoracic bronchogenic cysts was undertaken to detail their clinicopathologic and
      radiologic features. There were 18 male and 15 female patients between 12 and 77
      years of age with a mean age of 41 years. Thirty-one patients (94%) were
      symptomatic at the time of diagnosis and the chief complaint was chest pain
      (48.5%). Most of the cysts presented as homogeneous water-density shadows on
      standard chest radiographs. The location was intrapulmonary in 25 cases and
      mediastinal in 8 cases. Based on radiologic investigations, preoperative
      diagnosis of bronchogenic cyst was made in only 11 cases (33.34%). Surgical
      excision of the cyst was approached via thoracotomy in 32 cases and thoracoscopy
      in one case. Total excision of the cyst was performed in 31 cases and subtotal
      resection in 2 cases. Pathologic findings were consistent with bronchogenic cyst
      in all cases. During the follow-up period, which ranged between 1 month and 51
      months, all patients were symptom-free with no evidence of recurrence. Complete
      surgical resection is recommended for all bronchogenic cysts to establish
      diagnosis, alleviate symptoms, and prevent complications.

PMID- 18064523
TI  - New sex attractant composition for the click beetle Agriotes proximus: similarity
      to the pheromone of Agriotes lineatus.
AB  - While testing traps baited with a blend of geranyl octanoate and geranyl
      butanoate (pheromone components previously identified for Agriotes lineatus,
      Coleoptera, Elateridae) in Portugal and Bulgaria, large numbers of the closely
      related Agriotes proximus were captured. In the literature, two different
      compounds, (E,E)-farnesyl acetate and neryl isovalerate had previously been
      identified as pheromone components of A. proximus. Subsequent field tests,
      conducted in several European countries, revealed that A. proximus was weakly
      attracted to geranyl butanoate on its own, while A. lineatus was weakly attracted
      to geranyl octanoate on its own. However, the largest catches for both species
      were observed with a blend of both compounds. No A. proximus was caught in traps
      baited with the blend of (E,E)-farnesyl acetate and neryl isovalerate at any of
      the test sites. In electroantennographic studies, antennae of male A. proximus
      and A. lineatus both gave greater responses to geranyl butanoate than to geranyl
      octanoate, suggesting that the perception of these two compounds was similar for
      both species. A 1:1 blend of geranyl octanoate and geranyl butanoate can be used
      as a bait in traps for the detection and monitoring of both A. lineatus and A.
      proximus in many European countries.

PMID- 18064524
TI  - Tips for teachers of evidence-based medicine: making sense of diagnostic test
      results using likelihood ratios.

PMID- 18064525
TI  - Subcutaneous oxygen pressure in spontaneously breathing lean and obese
      volunteers: a pilot study.
AB  - BACKGROUND: Oxidative killing is the primary defense against surgical pathogens;
      risk of infection is inversely related to tissue oxygenation. Subcutaneous tissue
      oxygenation in obese patients is significantly less than in lean patients during
      general anesthesia. However, it remains unknown whether reduced intraoperative
      tissue oxygenation in obese patients results from obesity per se or from a
      combination of anesthesia and surgery. In a pilot study, we tested the hypothesis
      that tissue oxygenation is reduced in spontaneously breathing, unanesthetized
      obese volunteers. METHODS: Seven lean volunteers with a body mass index (BMI) of
      22 +/- 2 kg/m(2) were compared to seven volunteers with a BMI of 46 +/- 4
      kg/m(2). Volunteers were subjected to the following oxygen challenges: (1) room
      air; (2) 2 l/min oxygen via nasal prongs, (3) 6 l/min oxygen through a
      rebreathing face mask; (4) oxygen as needed to achieve an arterial oxygen
      pressure (arterial pO(2)) of 200 mmHg; and (5) oxygen as needed to achieve an
      arterial pO(2) of 300 mmHg. The oxygen challenges were randomized. Arterial pO(2)
      was measured with a continuous intraarterial blood gas analyzer (Paratrend 7);
      deltoid subcutaneous tissue oxygenation was measured with a polarographic
      microoxygen sensor (Licox). RESULTS: Subcutaneous tissue oxygenation was similar
      in lean and obese volunteers: (1) room air, 52 +/- 10 vs 58 +/- 8 mmHg; (2) 2
      l/min, 77 +/- 25 vs 79 +/- 24 mmHg; (3) 6 l/min, 125 +/- 43 vs 121 +/- 25 mmHg;
      (4) arterial pO(2) = 200 mmHg, 115 +/- 42 vs 144 +/- 23 mmHg; (5) arterial pO(2)
      = 300 mmHg, 145 +/- 41 vs 154 +/- 32 mmHg. CONCLUSION: In this pilot study, we
      could not identify significant differences in deltoid subcutaneous tissue oxygen
      pressure between lean and morbidly obese volunteers.

PMID- 18064527
TI  - Investigations on the biodegradation of alkylpolyglucosides by means of liquid
      chromatography-electrospray mass spectrometry.
AB  - The biodegradation of alkylpolyglucosides (APGs) was studied under the conditions
      of the OECD Screening Test with activated sludge as an inoculum. An influence of
      alkyl and sugar chain length on the biodegradation rate and a central scission
      pathway of the biodegradation were investigated. The liquid chromatography
      electrospray mass spectrometry technique was used for alkylpolyglucoside analysis
      and for identification and semiquantitative determination of metabolites. It was
      found that APGs with a longer alkyl chain were biodegraded faster than those with
      a shorter one. However, a longer sugar chain caused slower biodegradation of
      APGs. The central scission pathway of biodegradation was also confirmed.

PMID- 18064526
TI  - The impact of roux limb length on weight loss after gastric bypass.
AB  - BACKGROUND: Extending the length of the Roux limb (RL) in gastric bypass (GBP)
      may improve weight loss in super obese patients (body mass index [BMI] > 50
      kg/m(2)), but no consensus exists about the optimal length of the RL. We sought
      to determine the impact of RL length on weight loss in super obese patients 1
      year after GBP. MATERIALS AND METHODS: One-year weight loss outcomes were
      analyzed in all super obese patients who underwent consecutive and primary
      laparoscopic or open GBP between January 2003 and June 2006. Patients were
      divided into two groups according to RL length (100 vs. 150 cm). The RL length
      was at the discretion of the attending surgeon. Baseline and follow-up data were
      collected prospectively. Multiple linear regression was used to adjust for
      potential confounders in the weight loss outcomes. RESULTS: Twelve-month follow
      up data were available in 137 (85%) of 161 patients with a BMI >or= 50 who
      underwent GBP during the study period. An RL of 100 or 150 cm was used in 102
      (74.5%) and 35 patients (25.5%), respectively. In multivariate analysis, patients
      with the 150-cm RL lost more weight (68.5 vs. 55.3 kg, p < 0.01), had a greater
      change in BMI (25 vs. 21 kg/m(2), p = 0.01), and had greater excess weight loss
      (64 vs. 53%, p < 0.01). CONCLUSION: A 150-cm RL provides better weight loss
      outcomes in super obese patients at 1-year follow-up.

PMID- 18064528
TI  - The cardioprotective effects of alcohol consumption: does cardiac autonomic
      function play a role?
AB  - Moderate alcohol consumption has cardioprotective properties and several
      mechanisms have been proposed. In over 4,000 men and women from the Whitehall II
      study, mean heart rate variability levels were lowest among those consuming the
      most alcohol per week, but in multivariate analyses no statistical associations
      were found. The cardiac autonomic nervous system is unlikely to explain much of
      the cardioprotective properties of alcohol.

PMID- 18064529
TI  - Use of recommended medications after myocardial infarction in Austria.
AB  - Guidelines recommend long-term use of beta-blockers (BB), statins, and
      angiotensin-converting-enzyme-inhibitors or angiotensin-receptor-blockers
      (ACEI/ARB) after myocardial infarction (MI), but data on their use after
      discharge are scarce. From Austrian sickness funds claims, we identified all
      acute MI patients who were discharged within 30 days and who survived >or=120
      days after MI in 2004. We ascertained outpatient use of ACEI/ARBs, BBs, statins,
      and aspirin from all filled prescriptions between discharge and 120 days post MI.
      Comorbidities were ascertained from use of indicator drugs during the preceding
      year. Multivariate logistic regression was used to evaluate the independent
      determinants of study drug use. We evaluated 4,105 MI patients, whose mean age
      was 68.8 (+/-13.2) years; 59.5% were men. Within 120 days after MI, 67% filled
      prescriptions for ACE/ARBs, 74% for BBs, and 67% for statin. While 41% received
      all these classes and 34% two, 25% of patients received only one or none of these
      drugs. Older age and presence of severe mental illness were associated with lower
      use of all drug classes. Diabetics had greater ACEI/ARB use. Fewer BBs were used
      in patients with obstructive lung disease. Statin use was lower in patients using
      treatment for congestive heart failure (all P<0.001). We conclude that
      recommended medications were underused in Austrian MI survivors. Quality
      indicators should be established and interventions be implemented to ensure
      maximum secondary prevention after MI.

PMID- 18064530
TI  - CNTO 95, a fully human anti alphav integrin antibody, inhibits cell signaling,
      migration, invasion, and spontaneous metastasis of human breast cancer cells.
AB  - CNTO 95 is a fully human monoclonal antibody that recognizes alphav integrins.
      Previous studies have shown that CNTO 95 exhibits both anti-tumor and anti
      angiogenic activities (Trikha M et al., Int J Cancer 110:326-335, 2004). In this
      study we investigated the biological activities of CNTO 95 on breast tumor cells
      both in vitro and in vivo. In vitro treatment with CNTO 95 decreased the
      viability of breast tumor cells adhering to vitronectin. CNTO 95 inhibited tumor
      cell adhesion, migration, and invasion in vitro. CNTO 95 treatment also induced
      tyrosine dephosphorylation of focal adhesion kinase (FAK), and the docking
      protein paxillin that recruits both structural and signaling molecules to focal
      adhesions (Turner CE, Int J Biochem Cell Biol 30:955-959, 1998; O'Neil GM et al.,
      Trends Cell Biol 10:111-119, 2000). These results suggest that CNTO 95 inhibits
      breast tumor cell growth, migration and invasion by interruption of alphav
      integrin mediated focal adhesions and cell motility signals. In vivo studies of
      CNTO 95 were conducted in an orthotopic breast tumor xenograft model. Treatment
      with CNTO 95 resulted in significant inhibition of both tumor growth and
      spontaneous metastasis of MDA-MB-231 cells to the lungs. CNTO 95 also inhibited
      lung metastasis in a separate experimental (tail vein injection) model of
      metastasis. The results presented here demonstrate the anti-tumor and anti
      metastatic activities of CNTO 95 in breast cancer models and provide insight into
      the cellular and molecular mechanisms mediating its inhibitory effects on
      metastasis.

PMID- 18064531
TI  - Inhibition of RANKL blocks skeletal tumor progression and improves survival in a
      mouse model of breast cancer bone metastasis.
AB  - Bone metastases cause severe skeletal morbidity including fractures and
      hypercalcemia. Tumor cells in bone induce activation of osteoclasts, which
      mediate bone resorption and release of growth factors from bone matrix, resulting
      in a "vicious cycle" of bone breakdown and tumor proliferation. Receptor
      activator of NF-kappaB ligand (RANKL) is an essential mediator of osteoclast
      formation, function, and survival, and is blocked by a soluble decoy receptor,
      osteoprotegerin (OPG). In human malignancies that metastasize to bone,
      dysregulation of the RANK/RANKL/OPG pathway can increase the RANKL:OPG ratio, a
      condition which favors excessive osteolysis. In a mouse model of bone metastasis,
      RANKL protein levels in MDA-MB-231 (MDA-231) tumor-bearing bones were
      significantly higher than tumor-free bones. The resulting tumor-induced
      osteoclastogenesis and osteolysis was dose-dependently inhibited by recombinant
      OPG-Fc treatment, supporting the essential role for RANKL in this process. Using
      bioluminescence imaging in a mouse model of metastasis, we monitored the anti
      tumor efficacy of RANKL inhibition on MDA-231 human breast cancer cells in a
      temporal manner. Treatment with OPG-Fc in vivo inhibited growth of MDA-231 tumor
      cells in bony sites when given both as a preventative (dosed day 0) and as a
      therapeutic agent for established bone metastases (dosed day 7). One mechanism by
      which RANKL inhibition reduced tumor burden appears to be indirect through
      inhibition of the "vicious cycle" and involved an increase in tumor cell
      apoptosis, as measured by active caspase-3. Here, we demonstrate for the first
      time that OPG-Fc treatment of mice with established bone metastases resulted in
      an overall improvement in survival.

PMID- 18064532
TI  - Evaluations of physiological monitoring displays: a systematic review.
AB  - OBJECTIVE: The purpose of this paper is to present the findings from a systematic
      review of evaluation studies for physiologic monitoring displays, centered on
      empirical assessments across all available settings and samples. The findings
      from this review give readers the opportunity to examine past work across studies
      and set the stage for the design and conduct of future evaluations. METHODS: A
      broad literature search of the literature from 1991 to June 2007 on PubMed and
      PsycINFO databases was completed to locate data-based articles for physiologic
      monitoring device display evaluations. The results of this search plus several
      unpublished works yielded 23 publications and 31 studies. RESULTS: Participants
      were faster detecting an adverse event, making a diagnosis or a clinical decision
      in 18 of 31 studies. They showed improved accuracy in a clinical decision or
      diagnosis in 13 of 19 studies and they perceived a decreased mental workload in 3
      of 8 studies. Eighteen studies used a within subjects design (mean sample size
      16.5), and 9 studies used a between group design (mean group size 7.6). Study
      settings were usability laboratories for 15 studies and patient simulation
      laboratories for 6 studies. Study participants were anesthesiologists or
      anesthesiology residents for 19 studies and nurses for 5 studies. CONCLUSIONS:
      The advent of integrated graphical displays ushered a new era into physiological
      monitoring display designs. All but one study reported significant differences
      between traditional, numerical displays and novel displays; yet we know little
      about which graphical displays are optimal and why particular designs work.
      Future authors should use a theoretical model or framework to guide the study
      design, focus on other clinical study participants besides anesthesiologists,
      employ additional research methods and use more realistic and complex tasks and
      settings to increase external validity.

PMID- 18064533
TI  - Patterns of leukemia incidence in the United States by subtype and demographic
      characteristics, 1997-2002.
AB  - OBJECTIVE: Efforts to prevent leukemia have been hampered by an inability to
      identify significant risk factors. Exploring incidence patterns of leukemia
      subtypes by sex and race/ethnic group may generate new etiologic hypotheses and
      identify high-risk groups for further study. METHODS: Data from the North
      American Association of Central Cancer Registries for 1997-2002 were used to
      assess patterns of leukemia incidence by subtype, sex, age, race and ethnicity.
      RESULTS: A total of 144,559 leukemia cases were identified, including 66,067
      (46%) acute and 71,860 (50%) chronic leukemias. The highest rates of acute
      myeloid leukemia with and without maturation were observed in Asian-Pacific
      Islanders (API). Hispanics had a higher incidence of acute lymphocytic leukemia,
      particularly in childhood, and promyelocytic leukemia than did non-Hispanics.
      African-Americans had the highest rates of HTLV-1 positive adult T-cell
      leukemia/lymphoma. A sharp increase in the incidence of chronic myeloid leukemia
      was observed for both APIs and Hispanics, 85 years and older. CONCLUSION: Known
      risk factors are unlikely to explain the observed disparities in leukemia
      incidence. Further studies of differences in environmental and genetic risk
      factors in these populations by specific leukemia subtype may provide clues to
      the etiologies of these malignancies.

PMID- 18064534
TI  - Is thyroid autoimmunity a risk factor for developing primary myelodysplastic
      syndrome?
AB  - OBJECTIVE: Thyroid disease has been associated with leukemia and lymphoma. No
      previous study using clinical and laboratory data has explored whether thyroid
      disease and especially autoimmune thyroid disease (ATD) is associated with
      myelodysplastic syndrome (MDS) risk. In this case-control study, we investigated
      the association of ATD with MDS. METHODS: Our study included 101 cases with
      incident primary MDS confirmed by histology and cytogenetics, and 101 controls
      matched on gender and age, admitted for non-neoplastic and non-infectious
      diseases. All subjects were submitted to clinical, ultrasound thyroid evaluation
      and serum free T3, free T4, TSH, thyroglobulin, and thyroperoxidase antibodies
      determination. RESULTS: Adjusting for age, gender, and body mass index, there was
      statistically significant evidence that ATD is associated with increased risk of
      MDS (OR = 2.58, 95% CI 1.29-5.16). Interestingly, ATD starting from the remote
      past (more than 10 years from MDS onset) was positively associated with MDS risk
      (OR = 5.73. 95% CI 2.03-16.16). Mean serum levels of fT3, fT4, and thyroid
      antibodies were significantly higher in MDS patients and mean TSH serum levels
      were significantly lower in MDS patients than in controls (p < 0.05). CONCLUSION:
      Biological plausibility and empirical evidence highlights the importance of ATD
      in MDS etiopathogenesis. Further studies are needed to explore underlying
      mechanisms associating thyroid autoimmunity with leukemogenesis.

PMID- 18064535
TI  - Nested case-control study of occupational physical activity and prostate cancer
      among workers using a job exposure matrix.
AB  - OBJECTIVE: We conducted a nested case-control study of 362 cases diagnosed
      between 1 January 1988 and 31 December 1999, and 1,805 matched controls to
      examine the association between occupational physical activity and prostate
      cancer incidence among workers at a nuclear and rocket engine-testing facility in
      Southern California. METHODS: We obtained cancer incidence data from the
      California Cancer Registry and seven other state cancer registries. Data from
      company records were used to construct a job exposure matrix (JEM) for
      occupational physical activity during employment. Conditional logistic regression
      was used to estimate associations. RESULTS: With adjustment for occupational
      confounders, including socioeconomic status and trichloroethylene (TCE) exposure,
      high activity levels at work were inversely associated with prostate-cancer
      incidence among aerospace workers (odds ratio [OR] = 0.55; 95% CI = 0.32-0.95),
      but not among radiation workers (OR = 0.95; 95% CI = 0.43-2.1). CONCLUSIONS: Our
      results suggest that adult men who are more continually active at work may have a
      decreased risk of prostate cancer.

PMID- 18064536
TI  - Survey on fluoride, bromide and chloride contents in public drinking water
      supplies in Sicily (Italy).
AB  - Six hundred and sixty-seven water samples were collected from public drinking
      water supplies in Sicily and analysed for electric conductivity and for their Cl(
      ), Br(-) and F(-) contents. The samples were, as far as possible, collected
      evenly over the entire territory with an average sampling density of about one
      sample for every 7,600 inhabitants. The contents of Cl(-) and Br(-), ranging
      between 5.53 and 1,302 mg/l and between <0.025 and 4.76 mg/l respectively,
      correlated well with the electric conductivity, a parameter used as a proxy for
      water salinity. The highest values were found both along the NW and SE coasts,
      which we attributed to seawater contamination, and in the central part of Sicily,
      which we attributed to evaporitic rock dissolution. The fluoride concentrations
      ranged from 0.023 to 3.28 mg/l, while the highest values (only three exceeding
      the maximum admissible concentration of 1.5 mg/l) generally correlated either
      with the presence in the area of crystalline (volcanic or metamorphic) or
      evaporitic rocks or with contamination from hydrothermal activity. Apart from
      these limited cases of exceeding F(-) levels, the waters of public drinking water
      supplies in Sicily can be considered safe for human consumption for the analysed
      parameters. Some limited concern could arise from the intake of bromide-rich
      waters (about 3% exceeding 1 mg/l) because of the potential formation of
      dangerous disinfection by-products.

PMID- 18064537
TI  - Study of summer heat exposure at the ground services operations of a main
      international airport in Saudi Arabia.
AB  - Summer heat in coastal subtropical Jeddah, augmented by heat from operating
      ground servicing equipment in King Abdul-Aziz International Airport (KAAIA),
      presents a major occupational problem to ground service operators, particularly
      the air traffic control coordinator (ATCC), that hinders their work efficiency
      and induces health disorders to them. The present study was conducted to assess
      the magnitude of this problem and propose heat control strategy and remedial
      actions for the Saudi Arabian Airlines (SAUDIA). Heat parameters including air
      temperature (T (a)), wet bulb temperature (T (w)), globe temperature (T (g)) and
      air velocity were measured around serviced planes and in other locations used by
      ATCC, and the WBGT and the ATCC-WBGT-TWAs were computed. Mostly all the T (a)
      measurements, and many T (w) measurements, were higher than T (a) and T (w)
      forecasted by the Presidency of Meteorology and Environment (PME) due to heat
      dissipated from operating vehicles and equipment in service. The measured and PME
      forecasted parameters have good and medium linear correlations (T (a): r (2) =
      0.74 and T (w): r (2) = 0.64). The computed WBGT in the service stations around
      planes are considerably higher than the 25 and 27.5 degrees C recommended TLV(R)
      for non-acclimatized and acclimatized operators. However, the computed ATCC- WBGT
      TWA levels indicate that the shift-work-schedule which was recommended to be
      implemented by SAUDIA has successfully reduced their heat exposure to acceptable
      levels, except for a very few operators (6.7% exceeding WBGT-TLV(R) of 25 degrees
      C and 2.2% exceeding TLV(R) of 27.5 degrees C) for whom the shift-work schedules
      might be corrected to achieve safe heat exposure.

PMID- 18064538
TI  - A high-throughput Agrobacterium-mediated transformation system for the grass
      model species Brachypodium distachyon L.
AB  - In the ongoing process of developing Brachypodium distachyon as a model plant for
      temperate cereals and forage grasses, we have developed a high-throughput
      Agrobacterium-mediated transformation system for a diploid accession. Embryogenic
      callus, derived from immature embryos of the accession BDR018, were transformed
      with Agrobacterium tumefaciens strain AGL1 carrying two T-DNA plasmids, pDM805
      and pWBV-Ds-Ubi-bar-Ds. Transient and stable transformation efficiencies were
      optimised by varying the pre-cultivation period, which had a strong effect on
      stable transformation efficiency. On average 55% of 17-day-old calli co
      inoculated with Agrobacterium regenerated stable transgenic plants. Stable
      transformation frequencies of up to 80%, which to our knowledge is the highest
      transformation efficiency reported in graminaceous species, were observed. In a
      study of 177 transgenic lines transformed with pDM805, all of the regenerated
      transgenic lines were resistant to BASTA, while the gusA gene was expressed in
      88% of the transgenic lines. Southern blot analysis revealed that 35% of the
      tested plants had a single T-DNA integration. Segregation analysis performed on
      progenies of ten selected T(0) plants indicated simple Mendelian inheritance of
      the two transgenes. Furthermore, the presence of two selection marker genes, bar
      and hpt, on the T-DNA of pWBV-Ds-Ubi-bar-Ds allowed us to characterize the
      developed transformation protocol with respect to full-length integration rate.
      Even when not selected for, full-length integration occurred in 97% of the
      transformants when using bialaphos as selection agent.

PMID- 18064540
TI  - A clue to the origin of life: begin from making tools.
AB  - The small molecules already existing on the earth can be assembled to biological
      macromolecules in the presence of the suitable tool. A workman must sharpen his
      tools if he is to do his work well. The tool must be specific, delicate and
      automatic. Obviously, it is enzyme. Therefore, to explore the origin of life we
      must understand the origin of the manufacturing tool of biological macromolecules
      -the origin of enzymes. We can understand more about the origin and evolution
      procedures of enzymes from the NO2. NO2 can easily form the dimmer, N2O4. Four
      N2O4 molecules can coordinate with a suitable metal ion and form a plane super
      molecule with four N2O4 molecules. This supramolecule provides the basis for the
      appearance of enzymes: (1) It is the template for producing enzymes. (2) It
      provides the active centers for enzymes. (3) It provides for the enzymes with
      specific function of chiral selection. This supramolecule reacts with
      formaldehyde and porphyrin compound is gradually formed. Once suitable function
      groups are substituted on the porphyrin ring, enzymes are formed. The primitive
      environment of earth can easily produce NO2 and CH2O. Therefore, this might be
      one clue to the origin of life.

PMID- 18064539
TI  - Molecular characterization and mRNA transcript profile of vitellogenin in Chinese
      shrimp, Fenneropenaeus chinensis.
AB  - A full-length cDNA encoding vitellogenin (Vg) was cloned from Chinese shrimp,
      Fenneropenaeus chinensis using RACE method. The full-length cDNA consist of 7,942
      nucleotides including a 7,761 bp open reading frame, which encodes 2,587 amino
      acid residues. The deduced amino acid sequence showed high (from 94% to 37%)
      identity with other known crustacean Vgs. In addition, a consensus cleavage site
      (R-X-K/R-R) recognized by an endopeptidase and a member of subtilisin family of
      serine protease were identified in the deduced Vg precursor. RT-PCR analysis
      shown that Vg mRNA can be detected in both ovary and hepatopancreas of
      vitellogenic females but not in other experimental tissues including muscle,
      heart, lymph organ, gill, haemocytes and intestine. These results suggest that
      the Vg gene may be expressed exclusively in mature females, and both ovary and
      hepatopancreas are the possible tissues for Vg synthesis in F. chinensis. In
      addition, Vg gene is detected in genomic DNA of both females and males.

PMID- 18064541
TI  - NMR studies of the inclusion complex of cloprostenol sodium salt with beta
      cyclodextrin in aqueous solution.
AB  - PURPOSE: Cloprostenol sodium salt (referred as cloprostenol) may be used for the
      synchronization of estrous cycles in farm animal species. Cyclodextrins (CDs)
      have potential as drug delivery systems through the formation of inclusion
      complexes between CDs and drugs. This is the first study of the inclusion complex
      of cloprostenol with beta-cyclodextrin (beta-CD) in aqueous solution using NMR
      and 3D molecular dynamics simulations. METHODS: 1D proton NMR spectra of beta-CD,
      a complex of cloprostenol with beta-CD, and cloprostenol in D(2)O were assigned
      and confirmed. The cross relaxation interactions from ROESY were used as
      constraints for 3D molecular modeling studies. RESULTS: In the 2D ROESY of the
      complex, cross-peaks were observed between the aromatic protons of cloprostenol
      and protons of the beta-CD as well as between aliphatic protons and protons of
      the beta-CD. The stoichiometry of the complex was found that beta-CD forms a 1:1
      inclusion complex with cloprostenol. The association constant K was 968 +/- 120
      M(-1) at 298 K. CONCLUSIONS: Aromatic side and/or aliphatic side chains of the
      cloprostenol is included in the beta-CD while aliphatic side and/or aromatic side
      chains wraps around beta-CD, respectively. The molecular modeling also confirms
      that beta-CD forms a 1:1 inclusion complex with cloprostenol.

PMID- 18064542
TI  - Urge to gamble in a simulated gambling environment.
AB  - Cue reactivity, while increasingly recognized as a central feature of drug and
      alcohol addiction, is not well studied in gambling. We evaluated the urge to
      gamble in a simulated casino environment among frequent gamblers who alternated
      between cycles in which they observed others playing ten hands of Blackjack
      (first, third and fifth cycle) and cycles in which they played ten hands of
      Blackjack themselves (second and fourth cycle). The played cycles served as a
      manipulation for the observed cycles in terms of "priming" (having previously
      gambled in the environment vs. not) and "anticipation" (expecting more
      opportunities to gamble in the environment vs. not) and, thus, allowed these
      conditions: observed cycle 1 = anticipation (+) and prime (-); observed cycle 2 =
      anticipation (+) and prime (+); and observed cycle 3 = anticipation (-) and prime
      (+). Subjects' urge to gamble was greater in the gambling environment than in a
      neutral setting and both positive anticipation and positive priming increased cue
      reactivity within the gambling environment. The frequency of gambling outside of
      the study did not affect cue reactivity. However, a preference for Blackjack (vs.
      other types of gambling) and observing winning (vs. losing) hands were both
      associated with stronger cue reactivity in the study. These findings contribute
      to our understanding of pathological gambling.

PMID- 18064543
TI  - A chemosensing ensemble for the detection of cysteine based on the inner filter
      effect using a rhodamine B spirolactam.
AB  - A fluorescent chemosensing ensemble for the detection of cysteine is designed
      based on the fluorescence inner filter effect. The method employs the
      coordination of Cu(2+) ion with salicylaldehyde rhodamine B hydrazone (I), a
      colorless and non-fluorescent rhodamine B spirolactam derivative to form I
      Cu(II), a pink color but weakly fluorescent complex. When rhodamine B was
      introduced to the I-Cu(II) complex solution, the fluorescence signal of rhodamine
      B is dramatically decreased because of the fluorescence inner filter effect
      (IFE). Upon adding cysteine to the above solution, it can complex preferentially
      to Cu(2+) compared to I, and the I-Cu(II) complex dissociates, which thus
      decreases the fluorescence IFE of the solution, and in turn leading to the
      fluorescence increase of the chemosensing system. Based on the above mechanism, a
      fluorescent chemosensing ensemble for cysteine is developed. The fluorescence
      increase is linearly with cysteine concentration up to 10.0 mu mol L(-1), with a
      detection limit of 1.4 x 10(-7) mol L(-1) (3sigma). The optimal conditions of the
      proposed method were studied and the selectivity of the proposed method was
      investigated in this paper.

PMID- 18064544
TI  - Interactions of Nile blue with micelles, reverse micelles and a genomic DNA.
AB  - In this contribution we report studies on the nature of binding of a small
      ligand/drug Nile blue (NB) with sodium dodecyl sulfate (SDS) micelles, bis-(2
      ethylehexyl) sulfosuccinate (AOT)/isooctane reverse micelles (RM) and a genomic
      DNA extracted from Salmon sperm. With detailed steady state and picosecond
      resolved optical spectroscopic techniques, we examined the fluorescence quenching
      of the ligand upon complexation with the SDS monomers and DNA. Polarization
      analyzed picosecond-resolved fluorescence measurements reveal geometrical
      restriction on the probe in SDS micelles, AOT-RM and DNA. Steady state and time
      resolved studies on the probe in nanocages of AOT RM with various degrees of
      hydration (w(0)) reveal the existence of NB as two distinct species namely,
      neutral and cationic. This study confirms that the emission of NB in aqueous
      micelles and DNA solution is due to the cationic form of the drug. Our
      experiments clearly identified non-specific electrostatic and intercalative modes
      of interaction of the probe with the DNA at lower and higher DNA concentrations
      respectively. The nature of binding of NB in presence of the DNA and SDS micelles
      reveals that the binding affinity of the probe is higher with the micelles than
      with the DNA. The complex rigidity of NB with DNA and its fluorescence quenching
      with DNA elucidate a strong recognition mechanism between NB and DNA.

PMID- 18064545
TI  - Medicine and humanities: voicing connections.
AB  - Accepting as a given that the humanities disciplines are not product or "results"
      driven, this paper argues that the core of an interdisciplinary field of medicine
      and humanities, or medical humanities, is an interpretive enterprise that is not
      readily open to quantitative assessment. A more humanistically oriented medical
      practice can derive, however, from the process that produces new insights and
      works toward the development of a new, mutually shared, and humanizing language.

PMID- 18064546
TI  - The medical humanities today: humane health care or tool of governance?
AB  - The medical humanities have been presented as a panacea for medical reductionism;
      a means for 'humanizing' medicine. However, there is a lack of consensus about
      the appropriate contributing disciplines and how curricula should be taught and
      assessed. This special issue critically examines the role of the medical
      humanities in medical education and their potential to serve, inadvertently or
      otherwise, as a tool of governance. The contributors, who include medical
      educators and medical practitioners, employ a range of perspectives for analysing
      the pertinent issues.

PMID- 18064548
TI  - Criminal recidivism among juvenile offenders: testing the incremental and
      predictive validity of three measures of psychopathic features.
AB  - We studied the predictive, comparative, and incremental validity of three
      measures of psychopathic features (Psychopathy Checklist: Youth Version [PCL:YV];
      Antisocial Process Screening Device [APSD]; Childhood Psychopathy Scale [CPS])
      vis-a-vis criminal recidivism among 83 delinquent youth within a truly
      prospective design. Bivariate and multivariate analyses (Cox proportional hazard
      analyses) showed that of the three measures, the CPS was most consistently
      related to most types of recidivism in comparison to the other measures. However,
      incremental validity analyses demonstrated that all of the predictive effects for
      the measures of psychopathic features disappeared after conceptually relevant
      covariates (i.e., substance use, conduct disorder, young age, past property
      crime) were included in multivariate predictive models. Implications for the
      limits of these measures in applied juvenile justice assessment are discussed.

PMID- 18064549
TI  - Recognition and language in low functioning autism.
AB  - The hypothesis that a pervasive impairment of declarative memory contributes to
      language impairment in low functioning autism (LFA) was tested. Participants with
      LFA, high functioning autism (HFA), intellectual disability (ID) without autism,
      and typical development (TD) were given two recognition tests and four tests of
      lexical understanding. It was predicted that recognition would be impaired in the
      LFA group relative to the HFA and TD groups but not the ID group, and that
      recognition would correlate with lexical knowledge in the LFA group but none of
      the other groups. These predictions were supported except that the HFA group
      performed more similarly to the LFA group than expected, a finding interpreted in
      terms of selectively impaired episodic memory.

PMID- 18064550
TI  - The Autism Spectrum Quotient: Children's Version (AQ-Child).
AB  - The Autism Spectrum Quotient-Children's Version (AQ-Child) is a parent-report
      questionnaire that aims to quantify autistic traits in children 4-11 years old.
      The range of scores on the AQ-Child is 0-150. It was administered to children
      with an autism spectrum condition (ASC) (n = 540) and a general population sample
      (n = 1,225). Results showed a significant difference in scores between those with
      an ASC diagnosis and the general population. Receiver-operating-characteristic
      analyses showed that using a cut-off score of 76, the AQ-Child has high
      sensitivity (95%) and specificity (95%). The AQ-Child showed good test-retest
      reliability and high internal consistency. Factor analysis provided support for
      four of the five AQ-Child design subscales. Future studies should evaluate how
      the AQ-C performs in population screening.

PMID- 18064551
TI  - Autistic traits and cognitive performance in young people with mild intellectual
      impairment.
AB  - Cognitive performance and the relationship between theory of mind (TOM), weak
      central coherence and executive function were investigated in a cohort of young
      people with additional learning needs. Participants were categorized by social
      communication questionnaire score into groups of 10 individuals within the
      autistic spectrum disorder (ASD) range, 14 within the pervasive developmental
      disorder range and 18 with few autistic traits. The ASD group were significantly
      poorer than the other groups on a test of cognitive flexibility. In the ASD group
      only, there was a strong relationship between executive performance and TOM which
      remained after controlling for IQ. Our findings suggest that the relationship
      between cognitive traits may more reliably distinguish autism than the presence
      of individual deficits alone.

PMID- 18064552
TI  - Social interaction and repetitive motor behaviors.
AB  - Students with autism have difficulty initiating social interactions and may
      exhibit repetitive motor behavior (e.g., body rocking, hand flapping). Increasing
      social interaction by teaching new skills may lead to reductions in problem
      behavior, such as motor stereotypies. Additionally, self-monitoring strategies
      can increase the maintenance of skills. A multiple baseline design was used to
      examine whether multi-component social skills intervention (including peer
      training, social initiation instruction, and self-monitoring) led to a decrease
      in repetitive motor behavior. Social initiations for all participants increased
      when taught to initiate, and social interactions continued when self-monitoring
      was introduced. Additionally, participants' repetitive motor behavior was
      reduced. Changes in social behavior and in repetitive motor behavior maintained
      more than one month after the intervention ended.

PMID- 18064553
TI  - Aggressive and mating behaviors in two types of sex reversed mice: XY females and
      XX males.
AB  - Aggressive and mating behaviors were assessed in XX females, XY females, and XY
      males of the C57BL/6/J/Ei ("C57BL/6" or "B6") strain of mouse. The Y chromosome
      of the XY females derives from Mus domesticus poschiavinus and the Y chromosome
      of the XY males derives from Mus musculus. The poschiavinus Y in the C57BL/6
      background results in XY mice with either ovaries or ovotestes. Only those with
      ovaries were tested. These XY females appear to be endocrinologically identical
      to XX females. Aggressive and mating behaviors were also tested in XX males and
      XY males of the FVB/NtacfBR Odsex ("FVB") strain of mouse. The XX males have a
      transgene inserted 1 Mb upstream of the SOX9 gene, resulting in gonadal
      differentiation as a testis in the absence of a Y chromosome. C57BL/6 mice were
      tested for aggression in an instigated resident intruder paradigm and FVB/NtacfBR
      Odsex mice were tested for aggression in a neutral cage paradigm. Mice of both
      strains were tested with opponents of the same sex chromosome complement and
      gonadal sex. On the C57BL/6 background, the XY males were more aggressive than
      the XY and XX females, but there was no significant difference between the XX and
      XY females in aggression. On the FVB background, the XY and XX males were equally
      aggressive. Mice from both C57BL/6 and FVB backgrounds were tested for mating
      behaviors with females in hormonal estrus. On the C57BL/6 background, the XY
      males mounted more than the XY females, but there was no significant difference
      between the XY and XX females in mounting. On the FVB background, mounting,
      intromissions, and ejaculations were the same in XY and XX males. The
      implications of these findings for the effect of sex chromosome complement on sex
      differences in aggression and mating in mice are discussed.

PMID- 18064554
TI  - Measuring HIV-related stigma among Chinese service providers: confirmatory factor
      analysis of a multidimensional scale.
AB  - An HIV-related stigma scale for health care workers needs to be multidimensional
      in that it should encompass attitudes that might be experienced by the general
      public about people living with HIV/AIDS (PLWHA) (e.g., fear, shame, blame) and,
      further, specifically capture perceptions of appropriate professional care and
      medical responsibilities regarding PLWHA. A 17-item, 5-factor multidimensional
      HIV-related stigma scale was developed and validated using both exploratory and
      confirmatory factor analysis among 1,101 service providers in China. The sample
      was divided into a development sample (N = 551) and a validation sample (N =
      550). The fit of the final confirmatory factor model with five hypothesized
      subscales was excellent in both samples. The final stigma subscales included:
      Discrimination Intent at Work, Opinion about Health Care for HIV/AIDS Patients,
      Prejudiced Attitudes, Internalized Shame, and Fear of PLWHA.

PMID- 18064555
TI  - Factors associated with HIV viral load in a respondent driven sample in Los
      Angeles.
AB  - This study used a modified version of the Behavioral Model for Vulnerable
      Populations to examine the predisposing, enabling, and need factors associated
      with detectable viral load (VL). HIV status was measured using saliva and
      confirmed by blood. Of 797 persons enrolled, 193 were HIV positive and provided
      VL counts. A hierarchical multivariate logistic regression approach demonstrated
      that the predisposing factors of homelessness and recent substance abuse,
      particularly methamphetamine abuse, had a negative association with VL. The
      negative association of homelessness on VL was weakened with the introduction of
      enabling and need utilization factors. Mediation analysis indicated homelessness
      and HIV medication taking significantly associated with methamphetamine use as a
      predictor of detectable viral load. Guided policy to address substance abuse
      among those who are HIV positive is needed to improve biological outcomes.

PMID- 18064557
TI  - Religious coping and physiological, psychological, social, and spiritual outcomes
      in patients with HIV/AIDS: cross-sectional and longitudinal findings.
AB  - The present study investigated the relationships between positive religious
      coping (e.g., seeking spiritual support) and spiritual struggle (e.g., anger at
      God) versus viral load, CD4 count, quality of life, HIV symptoms, depression,
      self-esteem, social support, and spiritual well-being in 429 patients with
      HIV/AIDS. Data were collected through patient interview and chart review at
      baseline and 12-18 months later from four clinical sites. At baseline, positive
      religious coping was associated with positive outcomes while spiritual struggle
      was associated with negative outcomes. In addition, high levels of positive
      religious coping and low levels of spiritual struggle were associated with small
      but significant improvements over time. These results have implications for
      assessing religious coping and designing interventions targeting spiritual
      struggle in patients with HIV/AIDS.

PMID- 18064556
TI  - Alcohol use, intimate partner violence, sexual coercion and HIV among women aged
      15-24 in Rakai, Uganda.
AB  - Disinhibition due to alcohol may induce intimate partner violence and sexual
      coercion and increased risk of HIV infection. In a sample of 3,422 women aged 15
      24 from the Rakai cohort, Uganda, we examined the association between self
      reported alcohol use before sex, physical violence/sexual coercion in the past
      and prevalent HIV, using adjusted odds ratios (Adj OR) and 95% confidence
      intervals (95% CI). During the previous year, physical violence (26.9%) and
      sexual coercion (13.4%) were common, and alcohol use before sex was associated
      with a higher risk of physical violence/sexual coercion. HIV prevalence was
      significantly higher with alcohol consumption before sex (Adj OR = 1.45, 95% CI:
      1.06-1.98) and especially when women reported both prior sexual coercion and
      alcohol use before sex (Adj OR = 1.79, 95% CI: 1.25-2.56). Alcohol use before sex
      was associated with physical violence and sexual coercion, and both are jointly
      associated with HIV infection risk in young women.

PMID- 18064558
TI  - Associations between substance use, erectile dysfunction medication and recent
      HIV infection among men who have sex with men.
AB  - We conducted a case-control study to compare illicit substance and erectile
      dysfunction medication (EDM) use between recently HIV-infected and uninfected men
      who have sex with men (MSM). Eighty-six recently (previous 12 months) HIV
      infected MSM (cases) and 59 MSM who recently tested HIV-negative (controls)
      completed computer-assisted self-interviews. There were no statistical
      differences in demographics or number of sexual partners by HIV status. Cases
      were more likely than controls to report methamphetamine or nitrite use, but not
      EDM, gamma hydroxybutyrate, 3,4 methylenedioxymethamphetamine, cocaine, or
      marijuana use, in the previous 12 months and with their last three sexual
      partners in multivariate logistic regression models. Use of nitrites and
      amphetamine may increase HIV risk among MSM.

PMID- 18064559
TI  - Probability of HIV transmission during acute infection in Rakai, Uganda.
AB  - Accurate estimates of the probability of HIV transmission during various stages
      of infection are needed to inform epidemiological models. Very limited
      information is available about the probability of transmission during acute HIV
      infection. We conducted a secondary analysis of published data from the Rakai,
      Uganda seroconversion study. Mathematical and computer-based models were used to
      quantify the per-act and per-partnership transmission probabilities during acute
      and chronic HIV infection, and to estimate how many of the transmission events
      reported in the Rakai study were due to acute-phase HIV transmission. The average
      per-act transmission probability during acute infection equaled 0.03604 vs.
      0.00084 for chronic HIV infection. Overall, HIV was transmitted during acute
      infection in 46.5% of 23 "incident index partner couples." Acute-phase
      transmission accounted for 89.1% of all transmission events in the first 20
      months of follow-up. These results highlight the substantial risk of transmission
      during acute HIV infection.

PMID- 18064560
TI  - Effects of a psychotherapeutic drug prior authorization (PA) requirement on
      patients and providers: a providers' perspective.
AB  - This study describes the effects of a Texas Medicaid PA requirement for
      psychotherapeutic medications from the perspective of mental health care
      providers. Three focus groups were conducted and a content analysis was performed
      on the generated transcripts. Providers identified five categories of issues that
      are relevant to the PA process: (1) system/administrative factors; (2) costs/
      outcomes; (3) prescribing issues; (4) evaluation criteria; and (5) patient
      provider relationship and patient visit. Administrative burden and unintended
      patient outcomes were the most frequently reported issues related to PA. However,
      all five issues represent important factors that providers deal with when caring
      for patients with mental illness.

PMID- 18064561
TI  - Too old for IVF: are we discriminating against older women?
AB  - In vitro fertilization (IVF) in women of advanced age (>42 years) represents only
      5%, a comparatively minute part, of the national IVF experience in the United
      States (US). In view of evolving population dynamics, it, however, also
      represents proportionally a rather quickly expanding patient need. Because of
      access restrictions at many IVF programs, this market does not live up to its
      potential. As best demonstrated by the 2004 US National Summary and Fertility
      Clinic Report, which for the first time reported pregnancies and births above age
      45 year, IVF in women of advanced reproductive age represents a cutting edge area
      of interest for improving current IVF outcomes. Access to IVF should, therefore,
      not be withheld based on female age and/or baseline FSH levels. Instead, a
      definition of acceptable minimal pregnancy and life birth rates could be used to
      define the limits of offered access to IVF, independent of age and/or baseline
      FSH levels.

PMID- 18064562
TI  - Polymorphisms of Two Indels at the PRNP Gene in Three Beef Cattle Herds.
AB  - Bovine spongiform encephalopathy (BSE) is a transmissible fatal neurodegenerative
      disorder, presenting a characteristic spongiform degeneration of cattle brain due
      to the accumulation of a pathogenic and protease-resistant infectious protein
      (prion). Two deletion/insertion polymorphisms of the prion protein gene (23 bp at
      the promoter region and 12 bp at intron 1) were analyzed in three beef cattle
      herds (Aberdeen Angus, Charolais, and Franqueiro) to verify allele frequencies
      for possible use in selection of resistant animals. High frequencies of
      susceptibility alleles (23 and 12 bp deletion) and haplotype (23 del/12 del) were
      observed in the Aberdeen Angus and Charolais herds, but Franqueiro presented one
      of the highest frequencies of resistant alleles so far described. These data
      indicate the need for selection in Aberdeen Angus and Charolais breeds to
      increase the frequency of resistant animals in order to reduce the probabilities
      of BSE outbreaks in these populations.

PMID- 18064563
TI  - Treatment of depressive symptoms in patients with early stage breast cancer
      undergoing adjuvant therapy.
AB  - BACKGROUND: Studies have shown that there is a high prevalence of depression in
      cancer patients. Women with breast cancer may have an even higher risk of
      depression particularly in a postmenopausal or estrogen deficiency state. A small
      number of randomized controlled trials have examined the efficacy of
      antidepressants compared to that of a placebo in cancer patients, but some
      results have been difficult to interpret due to a heterogeneous patient group. In
      the current investigation, we screened newly diagnosed early stage breast cancer
      patients for depressive symptoms prior to the initiation of adjuvant therapy and
      investigated whether the oral antidepressant fluoxetine affected depressive
      symptoms, completion of adjuvant treatment, and quality of life. METHODS:
      Patients with newly diagnosed early stage breast cancer were screened for
      depressive symptoms prior to the initiation of adjuvant therapy. Patients with
      depressive symptoms were randomized to a daily oral fluoxetine or a placebo.
      Patients were then followed for 6 months and evaluated for quality of life,
      completion of adjuvant treatment, and depressive symptoms. RESULTS: A high
      percentage of patients with newly diagnosed early stage breast cancer were found
      to have depressive symptoms prior to the initiation of adjuvant therapy. The use
      of fluoxetine for 6 months resulted in an improvement in quality of life, a
      higher completion of adjuvant treatment (chemotherapy, hormonal therapy,
      chemotherapy plus hormonal therapy), and a reduction in depressive symptoms
      compared to patients who received placebo. CONCLUSIONS: An antidepressant should
      be considered for early stage breast cancer patients with depressive symptoms who
      are receiving adjuvant treatment.

PMID- 18064565
TI  - How common is fatigue in disease-free breast cancer survivors? A systematic
      review of the literature.
AB  - BACKGROUND: There is some debate in the literature as to whether fatigue persists
      in the long term in women who have completed adjuvant breast cancer treatment.
      METHODS: A systematic review was conducted in order to characterise and quantify
      the phenomenon of post treatment fatigue (PTF). RESULTS: There was a wide
      variation in the measures of fatigue used, duration of follow-up and type of
      comparison made. Overall 18 studies were identified with a follow-up period of
      between 4 months and 10 years. Fourteen studies demonstrated the presence of
      continued PTF and/or differences in fatigue levels compared to a reference
      population up to 5 years after treatment. One short-term study reported no
      increase in fatigue at 4 months. Three studies (with an average follow up period
      of longer than 5 years) did not identify overall quality of life differences in
      breast cancer survivors when compared with a reference population. However there
      were significant differences in measures of physical functioning and mental
      fatigue. CONCLUSION: The authors conclude that there is good evidence of PTF
      occurring up to 5 years after completion of adjuvant therapy.

PMID- 18064564
TI  - Inactivation of NF-kappaB by proteasome inhibition contributes to increased
      apoptosis induced by histone deacetylase inhibitors in human breast cancer cells.
AB  - Histone deacetylase inhibitors (HDACi) are a new class of anticancer agents that
      cause growth arrest, differentiation and/or apoptosis in many tumor cells. As
      acetylation regulates the activity of the anti-apoptotic transcription factor NF
      kappaB, we investigated whether the proteasome inhibitor MG-132 would inhibit NF
      kappaB activation and as a consequence potentiate HDACi-dependent apoptosis in
      breast cancer cells. We observed that the HDACi suberoylanilide hydroxamic acid
      (SAHA) or trichostatin A (TSA) induced cell death but also enhanced NF-kappaB
      activity. This increase of NF-kappaB activity was strongly reduced by the
      addition of MG-132. Moreover, MG-132 potentiates the HDACi-induced cell death
      that was associated with caspase-3 activation, and PARP cleavage. Induction of
      the stress related kinases JNK and p38 and the up-regulation of p21 and p27 were
      also observed after co-treatment of cells with HDACi and MG-132. Disruption of
      the NF-kappaB pathway by BAY 11-7085 or IkappaB-SR mimicked the action of MG-132
      in promoting HDACi-induced cell death. Thus, the combined treatment with HDACi
      and proteasome inhibitors potentiates apoptosis in breast cancer cells
      representing a novel strategy for breast cancer therapy.

PMID- 18064566
TI  - Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast
      density.
AB  - INTRODUCTION: High breast density is one of the strongest known risk factors for
      developing breast cancer. Insulin-like growth factor I (IGF-I) is a strong
      mitogen and has been suggested to increase breast cancer risk by increasing the
      amount of dense tissue in the female breast. OBJECTIVES: We wanted to investigate
      the effect of common variation in the IGF-1 gene on serum IGF-I levels and on
      breast density. DESIGN AND METHODS: Mammograms and blood samples of 1,928
      premenopausal participants of the Dutch Prospect-EPIC cohort were collected at
      baseline. Using a haplotype tagging approach, 16 single nucleotide polymorphisms
      (SNP) from three blocks covering the IGF-1 gene were genotyped in all study
      participants. Breast density was assessed using a quantitative computer-assisted
      method. For a subgroup of women, who went through menopause within 5 years after
      recruitment (n=656), premenopausal IGF-I levels and additionally postmenopausal
      breast density were determined. False positive report probabilities (FPRP) for
      statistically significant relations were calculated using the Wacholder method.
      RESULTS: The minor alleles of five SNPs in block 3 were significantly associated
      with elevated levels of IGF-I (rs9989002, rs2033178, rs7136446, rs978458, rs6220;
      P-values: 0.01-0.04). The same SNPs were related with modestly higher percent
      breast density before menopause and-in the subgroup of women that became
      postmenopausal during follow-up-with a modestly higher percent breast density
      after menopause. The most significant result, i.e. the relation between rs6220
      and IGF-I levels, had an FPRP<0.5 assuming prior probabilities of 0.01 and
      higher. CONCLUSION: Common genetic variation in the IGF-1 gene is related to
      circulating levels of IGF-I, but the relationship with breast density is
      indecisive.

PMID- 18064567
TI  - Prognosis of uterine corpus cancer after tamoxifen treatment for breast cancer.
AB  - Tamoxifen increases the risk of uterine corpus cancer. Since only few, mostly
      small, studies have examined prognosis of uterine corpus cancer following
      tamoxifen, we conducted a large retrospective cohort study to further investigate
      this. We examined histopathologic and immunohistochemical characteristics of 332
      patients with uterine corpus cancer following breast cancer, according to
      tamoxifen use. Survival was examined in the same patients combined with 309
      patients from a previous study with updated follow-up. Histological review of all
      cancers was performed. Long-term tamoxifen users showed a higher proportion of
      non-endometrioid tumors than non-users (32.7% vs. 17.4%, P=0.004), especially
      serous adenocarcinomas and carcinosarcomas. An increased proportion of FIGO stage
      III and IV tumors was also observed (20.0% vs. 11.3%, P=0.049). Within FIGO stage
      I, both short-term and long-term tamoxifen users showed a higher proportion of
      tumors limited to the endometrium than non-users (35.7% vs. 22.9%, P=0.049 and
      0.004 respectively). Uterine corpus cancers in long-term tamoxifen users were
      more often steroid receptor-negative (ERalpha, PRA and PRB, P<0.05) and P53
      positive (P=0.015). Three-year uterine corpus cancer-specific survival was worse
      for long-term tamoxifen users than for non-users (82% vs. 93% P=0.0001). The
      survival difference remained after adjustment for histopathologic and
      immunohistochemical characteristics (hazard ratio (HR) for >or=2 years
      tamoxifen=2.4; 95% CI=1.2-4.6). In conclusion, this large study clearly shows
      that tamoxifen-associated tumors have less favorable histological features and a
      worse survival. Our results can be applied when weighing risks and benefits of
      tamoxifen versus other hormonal agents used in the prevention and treatment of
      breast cancer.

PMID- 18064568
TI  - The significance of circulating epithelial cells in Breast Cancer patients by a
      novel negative selection method.
AB  - PURPOSE: A negative selection method for the enumeration and characterization of
      circulating epithelial/cancer cells (CCC) in Breast Cancer (BC) patients is
      described. This manual procedure yields reproducible results of high sensitivity
      and selectivity suitable for research laboratories. PATIENTS AND METHODS: We
      conducted a prospective blood sampling study in 105 women with stage 1-4 BC
      attending clinics at the University of Maryland Greenebaum Cancer Center to
      define the prevalence of CCC utilizing our sensitive double gradient
      centrifugation and magnetic cell sorting CCC detection and enumeration method.
      CCC were isolated and enumerated from 15 to 20 ml of venous blood drawn before
      the start of systemic therapy and periodically thereafter for up to 24 months.
      One or more CCC/sample was considered a positive result. RESULTS: We analyzed 487
      samples for the presence of CCC; the median number of samples/patient was 4
      (range 1-8). CCC were detected in 56% of patients, 19%-stage 1; 43%-stage 2; 46%
      stage 3; 83%-stage 4. The probability of being positive for the presence of CCC
      is significantly associated with the stage of cancer (P < 0.0001). The frequency
      of CCC positive patients and samples increased with the advancing stage of
      disease. Presence of more than 10 CCC/sample was associated with the decreased
      survival and increased probability of having metastatic disease P = 0.001.
      CONCLUSIONS: Increasing number of CCC/sample correlates with the adverse outcome
      and poorer survival (P < 0.0001). Our CCC test based on the negative selection
      procedure may provide valuable prognostic information.

PMID- 18064569
TI  - Evaluating the ROC performance of markers for future events.
AB  - Receiver operating characteristic (ROC) curves play a central role in the
      evaluation of biomarkers and tests for disease diagnosis. Predictors for event
      time outcomes can also be evaluated with ROC curves, but the time lag between
      marker measurement and event time must be acknowledged. We discuss different
      definitions of time-dependent ROC curves in the context of real applications.
      Several approaches have been proposed for estimation. We contrast retrospective
      versus prospective methods in regards to assumptions and flexibility, including
      their capacities to incorporate censored data, competing risks and different
      sampling schemes. Applications to two datasets are presented.

PMID- 18064570
TI  - A respiratory system model: parameter estimation and sensitivity analysis.
AB  - In this paper we compare several approaches to identifying certain key
      respiratory control parameters relying on data normally available from non
      invasive measurements. We consider a simple model of the respiratory control
      system and describe issues related to numerical estimates of key parameters
      involved in respiratory function such as central and peripheral control gains,
      transport delay, and lung compartment volumes. The combination of model-specific
      structure and limited data availability influences the parameter estimation
      process. Methods for studying how to improve the parameter estimation process are
      examined including classical and generalized sensitivity analysis, and eigenvalue
      grouping. These methods are applied and compared in the context of clinically
      available data. These methods are also compared in conjunction with specialized
      tests such as the minimally invasive single-breath CO2 test that can improve the
      estimation, and the enforced fixed breathing test, which opens the control loop
      in the system. The analysis shows that it is impossible to estimate central and
      peripheral gain simultaneously without usage of ventilation measurement and a
      controlled perturbation of the respiratory system, such as the CO2 test. The
      numerical results are certainly model dependent, but the illustrated methods, the
      nature of the comparisons, and protocols will carry over to other models and data
      configurations.

PMID- 18064571
TI  - Modeling heart rate regulation--part I: sit-to-stand versus head-up tilt.
AB  - In this study we describe a model predicting heart rate regulation during
      postural change from sitting to standing and during head-up tilt in five healthy
      elderly adults. The model uses blood pressure as an input to predict baroreflex
      firing-rate, which in turn is used to predict efferent parasympathetic and
      sympathetic outflows. The model also includes the combined effects of vestibular
      and central command stimulation of muscle sympathetic nerve activity, which is
      increased at the onset of postural change. Concentrations of acetylcholine and
      noradrenaline, predicted as functions of sympathetic and parasympathetic outflow,
      are then used to estimate the heart rate response. Dynamics of the heart rate and
      the baroreflex firing rate are modeled using a system of coupled ordinary delay
      differential equations with 17 parameters. We have derived sensitivity equations
      and ranked sensitivities of all parameters with respect to all state variables in
      our model. Using this model we show that during head-up tilt, the baseline firing
      rate is larger than during sit-to-stand and that the combined effect of
      vestibular and central command stimulation of muscle sympathetic nerve activity
      is less pronounced during head-up tilt than during sit-to-stand.

PMID- 18064572
TI  - Substance use, education, employment, and criminal activity outcomes of
      adolescents in outpatient chemical dependency programs.
AB  - Although the primary outcome of interest in clinical evaluations of addiction
      treatment programs is usually abstinence, participation in these programs can
      have a wide range of consequences. This study evaluated the effects of treatment
      initiation on substance use, school attendance, employment, and involvement in
      criminal activity at 12 months post-admission for 419 adolescents (aged 12 to 18)
      enrolled in chemical dependency recovery programs in a large managed care health
      plan. Instrumental variables estimation methods were used to account for
      unobserved selection into treatment by jointly modeling the likelihood of
      participation in treatment and the odds of attaining a certain outcome or level
      of an outcome. Treatment initiation significantly increased the likelihood of
      attending school, promoted abstinence, and decreased the probability of
      adolescent employment, but it did not significantly affect participation in
      criminal activity at the 12-month follow-up. These findings highlight the need to
      address selection in a non-experimental study and demonstrate the importance of
      considering multiple outcomes when assessing the effectiveness of adolescent
      treatment.

PMID- 18064573
TI  - Recent advances on pathogenesis and therapies in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by
      extensive fibrotic changes in various organs, including skin and lung. Although
      the etiology of SSc remains unknown, three major abnormalities, abnormal humoral
      immunity, microvasculature, and fibroblast dysfunctions are considered to play
      important roles. Significant progress has been made in understanding the
      pathogenesis on SSc, and has been also providing clues to the treatment for this
      disease. This review summarizes recent advances on the pathogenesis and new
      therapeutic strategy for SSc.

PMID- 18064574
TI  - Protective effects of phytoestrogen alpha-zearalanol on beta amyloid25-35 induced
      oxidative damage in cultured rat hippocampal neurons.
AB  - Although experimental evidence has shown that the neuroprotective effect from
      estrogen may benefit postmenopausal women, but the clinical use of estrogen was
      limited by the risk of increasing the cases of mammary and endometrial cancer.
      This study was designed to evaluate the neuroprotective effects of a novel
      phytoestrogen alpha-zearalanol (alpha-ZAL), on the cultured rat hippocampal
      neurons. Following a 24-h exposure of the cells to amyloid beta-peptide fragment
      25-35 (A beta 25-35), a significant reduction in cell survival and activities of
      total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as
      increased of malondialdehyde (MDA) were observed. Preincubation of the cells with
      alpha-ZAL or 17 beta-estradiol(17 beta-E2) prior to A beta 25-35 exposure
      elevated the cell survival and SOD and GSH-Px activities, and decreased the level
      of MDA. These data suggested that the phytoestrogen alpha-ZAL, like estrogen, may
      effectively antagonize A beta 25-35-induced cell toxicity, which might be
      beneficial for neurons.

PMID- 18064575
TI  - Expression of two old yellow enzyme homologues from Gluconobacter oxydans and
      identification of their citral hydrogenation abilities.
AB  - Two genes that encode proteins which share 30-35% sequence identity with yeast
      OYE (Old Yellow Enzyme, an NAD(P)H FMN-oxidoreductase), the well-studied
      archetype of the OYE protein family, have been identified in Gluconobacter
      oxydans M5. The two genes are localized in the chromosome and plasmid,
      respectively. Comparison of the deduced amino acid sequences of the enzymes with
      database entries revealed 75.1% similarity and 64.9% identity to that of the
      Pseudomonas syringae pv. glycinea NAD(P)H-dependent 2-cyclohexen-1-one reductase.
      The two proteins were expressed as His-tag fusion proteins in Escherichia coli
      and purified. The ability of the purified proteins to hydrogenate citral was
      identified. The results showed that the alpha,beta-double bond of citral cis
      isomer 'neral' could be stereoselectively reduced to produce citronellal by the
      purified OYE homologues.

PMID- 18064576
TI  - Investigating quantitation of phosphorylation using MALDI-TOF mass spectrometry.
AB  - Despite advances in methods and instrumentation for analysis of phosphopeptides
      using mass spectrometry, it is still difficult to quantify the extent of
      phosphorylation of a substrate because of physiochemical differences between
      unphosphorylated and phosphorylated peptides. Here we report experiments to
      investigate those differences using MALDI-TOF mass spectrometry for a set of
      synthetic peptides by creating calibration curves of known input ratios of
      peptides/phosphopeptides and analyzing their resulting signal intensity ratios.
      These calibration curves reveal subtleties in sequence-dependent differences for
      relative desorption/ionization efficiencies that cannot be seen from single-point
      calibrations. We found that the behaviors were reproducible with a variability of
      5-10% for observed phosphopeptide signal. Although these data allow us to begin
      addressing the issues related to modeling these properties and predicting
      relative signal strengths for other peptide sequences, it is clear that this
      behavior is highly complex and needs to be further explored.

PMID- 18064577
TI  - Ni(+) reactions with aminoacetonitrile, a potential prebiological precursor of
      glycine.
AB  - The gas-phase reactions between Ni(+) ((2)D(5/2)) and aminoacetonitrile, a
      molecule of prebiological interest as possible precursor of glycine, have been
      investigated by means of mass spectrometry techniques. The mass-analyzed ion
      kinetic energy (MIKE) spectrum reveals that the adduct ions [NC--CH(2)--NH(2),
      Ni(+)] spontaneously decompose by loosing HCN, H(2), and H(2)CNH, the loss of
      hydrogen cyanide being clearly dominant. The structures and bonding
      characteristics of the aminoacetonitrile-Ni(+) complexes as well as the different
      stationary points of the corresponding potential energy surface (PES) have been
      theoretically studied by density functional theory (DFT) calculations carried out
      at B3LYP/6-311G(d,p) level. A cyclic intermediate, in which Ni(+) is bisligated
      to the cyano and the amino group, plays an important role in the unimolecular
      reactivity of these ions, because it is the precursor for the observed losses of
      HCN and H(2)CNH. In all mechanisms associated with the loss of H(2), the metal
      acts as hydrogen carrier favoring the formation of the H(2) molecule. The
      estimated bond dissociation energy of aminoacetonitrile-Ni(+) complexes (291 kJ
      mol(-1)) is larger than those measured for other nitrogen bases such as pyridine
      or pyrimidine and only slightly smaller than that of adenine.

PMID- 18064578
TI  - [Nepsilon-(gamma-glutamyl) lysine] as a potential biomarker in neurological
      diseases: new detection method and fragmentation pathways.
AB  - Protein aggregates are characteristic of a number of diseases of the central
      nervous system such as diseases of polyQ expansion. Covalent bonds formed by the
      action of transglutaminase are thought to participate in the stabilization of
      these aggregates. Transglutaminase catalyzes the formation of cross-links between
      the side chains of glutaminyl and lysyl residues of polypeptides. Identification
      of the isodipeptide N(epsilon)-(gamma-glutamyl) lysine (iEK) in terminal
      proteolytic digests of neuronal aggregates would demonstrate participation of
      transglutaminase in neurological diseases. In order to identify and quantify the
      iEK present in the brain of patients with neurological disease, a method
      combining liquid chromatography and multistep mass spectrometry was developed.
      Because isobaric peptides of iEK could be present in the digest of aggregated
      proteins, the choice of fragment diagnostic ions was crucial. These ions were
      identified by mass spectrometry on sodiated iEK, which was derivatized on the
      carboxylic functions and terminal amines in order to improve sensitivity.
      Deuterated molecules as well as (13)C(6)- and (15)N(2)-isotopomers were used to
      derive filiations in the multistep fragmentations. The main fragmentation
      patterns have been identified, so that two ions (m/z 396 [MH - 56-42 u](+) and
      350 [MH - 56-88 u](+)) are shown to be adequate markers for quantitation
      experiments. In order to gain a better understanding of the fragmentation
      processes, detailed quantum chemical calculations have been performed at levels
      which are expected to provide good accuracy. A thorough study has been carried
      out with a reduced model in which only the 'active' part of the molecule is
      retained. This allowed obtaining full mechanistic details on the pathways leading
      to a number of observed fragments. In particular, it has been shown that losses
      of 87 and 88 u from A(+) = [MH - 56 u](+) are competitive. Computations on the
      entire derivatized isodipeptide have been used to validate the use of the smaller
      model in order to obtain reliable energetics and mechanisms.

PMID- 18064579
TI  - Cell culture-produced hepatitis C virus impairs plasmacytoid dendritic cell
      function.
AB  - Previous studies suggested a functional impairment of dendritic cells (DCs) in
      patients with chronic hepatitis C. To investigate whether this effect was
      mediated by a direct interaction of hepatitis C virus (HCV) with DCs, we studied
      the effects of infectious cell culture-produced hepatitis C virus (HCVcc) on
      peripheral blood mononuclear cells (PBMCs), ex vivo isolated plasmacytoid, and
      myeloid DCs and in vitro generated monocyte-derived DCs of healthy blood donors.
      HCVcc inhibited toll-like receptor (TLR)-9 (CpG and herpes simples virus)
      mediated interferon alpha (IFN-alpha) production by peripheral blood mononuclear
      cells (PBMC) and plasmacytoid DCs. This inhibitory effect was also observed in
      response to ultraviolet (UV)-inactivated, noninfectious HCVcc, and it was not
      abrogated by neutralizing antibodies, and thus did not appear to require DC
      infection. Influenza A virus restored maturation and TLR9-mediated IFN-alpha
      production. In contrast to its effect on plasmacytoid DCs, HCVcc did not inhibit
      TLR3-mediated and TLR4-mediated maturation and interleukin (IL)-12, IL-6, IL-10,
      interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha)
      production by myeloid DCs and monocyte-derived DCs. Likewise, HCVcc did neither
      alter the capacity of myeloid DCs nor monocyte-derived DCs to induce CD4 T cell
      proliferation. Whereas phagocytosis of apoptotic hepatoma cells resulted in DC
      maturation, this effect was independent of whether the phagocytosed Huh7.5.1
      cells were infected with HCVcc. In contrast to HCVcc, vaccinia virus inhibited
      maturation and TNF-alpha expression of myeloid DC as well as maturation and IL-6
      and IL-10 production of monocyte-derived DC. CONCLUSION: HCVcc inhibited
      plasmacytoid DCs but not myeloid-derived and monocytoid-derived DCs via a direct
      interaction that did not require infection. The response of plasmacytoid DCs to
      influenza A virus infection was not impaired.

PMID- 18064580
TI  - Toward understanding nonparticipation in sigmoidoscopy screening for colorectal
      cancer.
AB  - Understanding the reasons for nonparticipation in cancer screening may give clues
      about how to improve compliance. However, limited cooperation has hampered
      research on nonparticipant profiles. We took advantage of Sweden's comprehensive
      demographic and health care registers to investigate characteristics of all
      participants and nonparticipants in a pilot program for colorectal cancer
      screening with sigmoidoscopy. A population-based sample of 1986 Swedish residents
      59-61 years old was invited. Registers provided information on each individual's
      gender, country of birth, marital status, education, income, hospital contacts,
      place of residence, distance to screening center and cancer within the family.
      Odds ratios (ORs) with 95% confidence intervals (CIs), modeled with multivariable
      logistic regression, estimated the independent associations between each
      background factor and the propensity for nonparticipation after control for the
      effects of other factors. All statistical tests were 2-sided. Being male (OR =
      1.27, 95% CI = 1.03-1.57, relative to female), unmarried or divorced (OR = 1.69,
      95% CI = 1.23-2.30 and OR = 1.49, 95% CI = 1.14-1.95, respectively, relative to
      married) and having an income in the lowest tertile (OR = 1.68, 95% CI = 1.27
      2.23, relative to highest tertile) was associated with increased
      nonparticipation. Living in the countryside or in small communities and having a
      documented family history of colorectal cancer was associated with better
      participation. Distance to the screening center did not significantly affect
      participation, nor did recent hospital care consumption or immigrant status. To
      increase compliance, invitations must appeal to men, unmarried or divorced people
      and people with low socioeconomic status.

PMID- 18064581
TI  - Effects of meteorology, astronomical variables, location and human disturbance on
      the singing apes: Hylobates albibarbis.
AB  - Gibbons are characterized by their species-specific calls. The frequency of
      singing is known to be affected by rainfall, with singing occurring less in the
      wet season. I investigate the hypothesis that gibbon singing is also affected by
      the natural light-dark cycle, and by the changing light intensity and air quality
      resulting from the smoke haze which blankets the Indonesian island of Borneo on a
      yearly basis. I compare three singing variables-onset of singing, average
      duration of singing bout and number of female great calls produced during the dry
      season of 2006 when there was no smoke haze (June-August) and when there was
      smoke haze present (September-November). I present evidence which indicates that
      the changes in singing behavior are affected by changes in rainfall and smoke
      intensity but not by other meteorological factors (i.e. wind and light intensity)
      or changing astronomical cues (light intensity, month, time of sunrise, time of
      moonrise, nocturnal illumination index, day length and night length). The
      possible long-term effects of this on gibbon behavior and territoriality are
      discussed. The need to carry out more research on the long-term effects of the
      smoke haze on wildlife behavior and possible solutions to the problem are
      discussed.

PMID- 18064582
TI  - Frequency domain connectivity identification: an application of partial directed
      coherence in fMRI.
AB  - Functional magnetic resonance imaging (fMRI) has become an important tool in
      Neuroscience due to its noninvasive and high spatial resolution properties
      compared to other methods like PET or EEG. Characterization of the neural
      connectivity has been the aim of several cognitive researches, as the
      interactions among cortical areas lie at the heart of many brain dysfunctions and
      mental disorders. Several methods like correlation analysis, structural equation
      modeling, and dynamic causal models have been proposed to quantify connectivity
      strength. An important concept related to connectivity modeling is Granger
      causality, which is one of the most popular definitions for the measure of
      directional dependence between time series. In this article, we propose the
      application of the partial directed coherence (PDC) for the connectivity analysis
      of multisubject fMRI data using multivariate bootstrap. PDC is a frequency domain
      counterpart of Granger causality and has become a very prominent tool in EEG
      studies. The achieved frequency decomposition of connectivity is useful in
      separating interactions from neural modules from those originating in scanner
      noise, breath, and heart beating. Real fMRI dataset of six subjects executing a
      language processing protocol was used for the analysis of connectivity.

PMID- 18064583
TI  - Differential parametric modulation of self-relatedness and emotions in different
      brain regions.
AB  - Our sense of self is strongly colored by emotions although at the same time we
      are well able to distinguish affect and self. Using functional magnetic resonance
      imaging, we here tested for the differential effects of self-relatedness and
      emotion dimensions (valence, intensity) on parametric modulation of neural
      activity during perception of emotional stimuli. We observed opposite parametric
      modulation of self-relatedness and emotion dimensions in the dorsomedial
      prefrontal cortex and the ventral striatum/nucleus accumbens, whereas neural
      activity in subcortical regions (tectum, right amygdala, hypothalamus) was
      modulated by self-relatedness and emotion dimensions in the same direction. In
      sum, our results demonstrate that self-relatedness is closely linked to emotion
      dimensions of valence and intensity in many lower subcortical brain regions
      involved in basic emotional systems and, at the same time, distinct from them in
      higher cortical regions that mediate cognitive processes necessary for becoming
      aware of one's self, for example self-consciousness. Hum

PMID- 18064584
TI  - Hemispheric and gender related differences in the midcingulum bundle: a DTI
      study.
AB  - The midcingulate cortex and therefore the underlying midcingulum bundle (MCB) as
      well play a major role in attention. Although a specific structure's function
      does strongly depend on its neuroanatomical characteristics, research assessing
      the morphological variability of the midcingulate region is rather sparse. The
      present study examined the micro- and macrostructure of the MCB in both
      hemispheres by means of diffusion-tensor imaging. Besides, effects of gender
      (Female = 40, Male = 39) and handedness (Lefthanders = 45, Righthanders = 34)
      were assessed as well. Measures of fractional anisotropy, mean diffusion, as well
      as the white matter volumes of the MCBs were assessed. By integration of multi
      modal images, the MCB was isolated and confounding with callosal fibers was
      avoided. Evidence was found indicating differences between hemispheres and gender
      regarding both volume and microstructural characteristics of the MCB.
      Interestingly, gender-related effects seem to be substantially associated with
      variations in individual brain volumes. Handedness did not emerge as relevant
      factor in the analyses. These findings might indicate a higher functional
      connectivity of the left MCB and in males as compared to females.

PMID- 18064585
TI  - Neurofunctional modulation of brain regions by distinct forms of motor cognition
      and movement features.
AB  - Extrastriate, parietal, and frontal brain regions are differentially involved in
      distinct kinds of body movements and motor cognition. Using functional magnetic
      resonance imaging, we investigated the neural mechanisms underlying the
      observation and mental imagery of meaningful face and limb movements with or
      without objects. The supplementary motor area was differentially recruited by the
      mental imagery of movements while there were differential responses of the
      extrastriate body area (EBA) during the observation conditions. Contrary to most
      previous reports, the EBA responded to face movements, albeit to a lesser degree
      than to limb movements. The medial wall of the intraparietal sulcus and adjacent
      intraparietal cortex was selectively recruited by the processing of meaningful
      upper limb movements, irrespective of whether these were object-related or not.
      Besides reach and grasp movements, the intraparietal sulcus may thus be involved
      in limb gesture processing, that is, in an important aspect of human social
      communication. We conclude that subregions of a frontal-parietal network
      differentially interact during the cognitive processing of body movements
      according to the specific motor-related task at hand and the particular movement
      features involved.

PMID- 18064586
TI  - Assessment of the increase in variability when combining volumetric data from
      different scanners.
AB  - In multicenter MRI studies, pooling of volumetric data requires a prior
      evaluation of compatibility between the different machines used. We tested the
      compatibility of five different scanners (2 General Electric Signa, 2 Siemens
      Symphony, and a Philips Gyroscan) at five different sites by repeating the scans
      of five volunteers at each of the sites. Using a semiautomatic method based on
      the Talairach atlas, and SPM algorithms for tissue segmentation (multimodal T1
      and T2, or T1-only), we obtained volume measurements of the main brain lobes
      (frontal, parietal, occipital, temporal) and for each tissue type. Our results
      suggest that pooling of multisite data adds small error for whole brain
      measurements, intersite coefficient of variation (CV) ranging from 1.8 to 5.2%,
      respectively, for GM and CSF. However, in the occipital lobe, intersite CV can be
      as high as 11.7% for WM and 17.3% for CSF. Compared with the intersite, intrasite
      CV values were always much lower. Whenever possible, T1 and T2 tissue
      segmentation methods should be used because they yield more consistent volume
      measurements between sites than T1-only, especially when some of the scans were
      obtained with different sequence parameters and pixel size from those of the
      other sites. Our study shows that highest compatibility among scanners would be
      obtained using equipments of the same manufacturer and also image acquisition
      parameters as similar as possible. After validation, data from a specific ROI or
      scanner showing values markedly different from the other sites might be excluded
      from the analysis.

PMID- 18064587
TI  - Effects of acute dehydration on brain morphology in healthy humans.
AB  - Dehydration can affect brain structure which has important implications for human
      health. In this study, we measured regional changes in brain structure following
      acute dehydration. Healthy volunteers received a structural MRI scan before and
      after an intensive 90-min thermal-exercise dehydration protocol. We used two
      techniques to determine changes in brain structure: a manual point counting
      technique using MEASURE, and a fully automated voxelwise analysis using SIENA.
      After the exercise regime, participants lost (2.2% +/- 0.5%) of their body mass.
      Using SIENA, we detected expansion of the ventricular system with the largest
      change occurring in the left lateral ventricle (P = 0.001 corrected for multiple
      comparisons) but no change in total brain volume (P = 0.13). Using manual point
      counting, we could not detect any change in ventricular or brain volume, but
      there was a significant correlation between loss in body mass and third
      ventricular volume increase (r = 0.79, P = 0.03). These results show ventricular
      expansion occurs following acute dehydration, and suggest that automated
      longitudinal voxelwise analysis methods such as SIENA are more sensitive to
      regional changes in brain volume over time compared with a manual point counting
      technique.

PMID- 18064589
TI  - An evaluation of spatial thresholding techniques in fMRI analysis.
AB  - Many fMRI experiments have a common objective of identifying active voxels in a
      neuroimaging dataset. This is done in single subject experiments, for example, by
      performing individual voxel-wise tests of the null hypothesis that the observed
      time course is not significantly related to an assigned reference function. A
      voxel activation map is then constructed by applying a thresholding rule to the
      resulting statistics (e.g., t-statistics). Typically the task-related activation
      is expected to occur in clusters of voxels rather than in isolated single voxels.
      A variety of spatial thresholding techniques have been proposed to reflect this
      belief, including smoothing the raw t-statistics, cluster size inference, and
      spatial mixture modeling. We study two aspects of these spatial thresholding
      procedures applied to single subject fMRI analysis through simulation. First, we
      examine the performance of these procedures in terms of sensitivity to detect
      voxel activation, using receiver operating characteristic curves. Second, we
      consider the accuracy of these spatial thresholding procedures in estimation of
      the size of the activation region, both in terms of bias and variance. The
      findings indicate that smoothing has the highest sensitivity to modest magnitude
      signals, but tend to overestimate the size of the activation region. Spatial
      mixture models estimate the size of a spatially distributed activation region
      well, but may be less sensitive to modest magnitude signals, indicating that
      additional research into more sensitive spatial mixture models is needed.
      Finally, the methods are illustrated with a real bilateral finger-tapping fMRI
      experiment.

PMID- 18064588
TI  - Detecting brain growth patterns in normal children using tensor-based
      morphometry.
AB  - Previous magnetic resonance imaging (MRI)-based volumetric studies have shown age
      related increases in the volume of total white matter and decreases in the volume
      of total gray matter of normal children. Recent adaptations of image analysis
      strategies enable the detection of human brain growth with improved spatial
      resolution. In this article, we further explore the spatio-temporal complexity of
      adolescent brain maturation with tensor-based morphometry. By utilizing a novel
      non-linear elastic intensity-based registration algorithm on the serial
      structural MRI scans of 13 healthy children, individual Jacobian growth maps are
      generated and then registered to a common anatomical space. Statistical analyses
      reveal significant tissue growth in cerebral white matter, contrasted with gray
      matter loss in parietal, temporal, and occipital lobe. In addition, a linear
      regression with age and gender suggests a slowing down of the growth rate in
      regions with the greatest white matter growth. We demonstrate that a tensor-based
      Jacobian map is a sensitive and reliable method to detect regional tissue changes
      during development.

PMID- 18064591
TI  - Intra-community infanticide and forced copulation in spider monkeys: a multi-site
      comparison between Cocha Cashu, Peru and Punta Laguna, Mexico.
AB  - We describe two cases of infanticide, two suspected infanticides, and a forced
      copulation by familiar resident males in two populations of wild spider monkeys
      (Ateles belzebuth chamek and A. geoffroyi yucatanensis). These are the first
      known infanticides and forced copulation in spider monkeys. Data were gathered
      from four neighboring communities of spider monkeys in Manu National Park at the
      Cocha Cashu Biological Station, Peru and two communities in the Otoch Ma'ax Yetel
      Kooh Reserve at Punta Laguna, Mexico, during intensive field studies of over
      2,000 hr each. These are rare behaviors, but results suggest that mating history
      and sexual coercion are important in spider monkey social relationships.

PMID- 18064590
TI  - Heritability of "small-world" networks in the brain: a graph theoretical analysis
      of resting-state EEG functional connectivity.
AB  - Recent studies have shown that resting-state functional networks as studied with
      fMRI, EEG, and MEG may be so-called small-world networks. We investigated to what
      extent the characteristic features of small-world networks are genetically
      determined. To represent functional connectivity between brain areas, we measured
      resting EEG in 574 twins and their siblings and calculated the synchronization
      likelihood between each pair of electrodes. We applied a threshold to obtain a
      binary graph from which we calculated the clustering coefficient C (describing
      local interconnectedness) and average path length L (describing global
      interconnectedness) for each individual. Modeling of MZ and DZ twin and sibling
      resemblance indicated that across various frequency bands 46-89% of the
      individual differences in C and 37-62% of the individual differences in L are
      heritable. It is asserted that C, L, and a small-world organization are viable
      markers of genetic differences in brain organization.

PMID- 18064592
TI  - Two-scale, three-phase theory for swelling drug delivery systems. Part II: flow
      and transport models.
AB  - Darcy's law and Fick's law of Part I are combined with bulk and species
      conservation of mass equations, respectively, to obtain flow and transport models
      for swelling drug delivery systems. The model identifies three distinct regimes
      and makes the appropriate simplifying assumptions for each. The result is a set
      of highly nonlinear, coupled, integro-partial differential equations. The
      advantage of this model is that it can be easily modified to account for multiple
      simplified scenarios and geometries. As an example, boundary conditions are given
      for a radially symmetric drug delivery device.

PMID- 18064593
TI  - Sphingosine kinase 1 gene transfer reduces postoperative peritoneal adhesion in
      an experimental model.
AB  - BACKGROUND: Recovery of the surgically damaged mesothelial cell layer is a major
      process in reducing postoperative peritoneal adhesions. Sphingosine kinase (SPK)
      1 is a signalling molecule involved in the regulation of proliferation and
      migration of various cell types. This study determined the effect of SPK-1 gene
      transfer on the recovery of damaged mesothelial cells and on peritoneal adhesion
      formation after surgery. METHODS: Rat mesothelial cells were isolated and
      characterized by their expression of cytokeratin and vimentin. Their migration
      was determined by scratch wound motility assay. Cellular SPK-1 activity was
      measured by [gamma-32P]adenosine 5'-triphosphate incorporation. Wistar rats
      underwent laparotomy with subsequent caecum or uterine horn abrasion. Rats were
      randomized to either SPK-1 gene (Ad-SPK-1) transfer or control groups. The
      animals were killed 14 days after operation and peritoneal adhesions were graded.
      RESULTS: Adenovirus-mediated SPK-1 gene transfer increased the cellular SPK-1
      activity of mesothelial cells, leading to enhanced migration. Median adhesion
      scores were significantly lower in the Ad-SPK-1 group than in controls in both
      rat caecum (0.98 versus 2.60; P < 0.001) and rat uterine horn (0.28 versus 1.83;
      P < 0.001) models. CONCLUSION: Adenovirus-mediated SPK-1 gene transfer promotes
      recovery of the surgically damaged mesothelial cell layer and prevents
      postoperative peritoneal adhesion formation.

PMID- 18064594
TI  - Process analytical technology: nondestructive evaluation of cyclosporine A and
      phospholipid solid dispersions by near infrared spectroscopy and imaging.
AB  - The objective of this study was to evaluate near infrared (NIR) spectroscopy and
      imaging as approaches to assess phospholipid compartment within its solid
      dispersion with cyclosporine A (CyA). By varying dimyristoyl phosphatidylcholine
      (DMPC) to CyA weight ratio, five batches were prepared by the kneading technique
      and characterized by DSC and FTIR. A drug/DMPC ratio of 50:1 provided an enhanced
      dissolution of CyA. FTIR spectra and DSC thermograms revealed a significant
      interaction between the drug and DMPC which suggested incorporation of CyA within
      the formed DMPC liposomes. The developed NIR calibration model was able to assess
      DMPC concentrations within the kneaded products. The calibration and prediction
      linear plots showed slopes of 0.9711 and 0.9915, offsets of 0.1247 and 0.1080,
      correlation coefficients of 0.9854 and 0.9889 and root mean square standard
      errors of 0.43% and 0.42%, respectively. In contrast, NIR spectral imaging was
      capable of clearly distinguishing the kneaded products, both qualitatively and
      quantitatively. NIR imaging revealed the poor powder blending efficiency of the
      method used to prepare physical mixture compared to the efficient distribution of
      the kneaded products. In conclusion, NIR spectral imaging system provides a rapid
      approach for acquiring high-resolution spatial and spectral information on solid
      dispersions.

PMID- 18064595
TI  - Quantitative structure-mobility relationship study of a diverse set of organic
      acids using classification and regression trees and adaptive neuro-fuzzy
      inference systems.
AB  - A quantitative structure-mobility relationship was developed to accurately
      predict the electrophoretic mobility of organic acids. The absolute
      electrophoretic mobilities (mu(0)) of a diverse dataset consisting of 115
      carboxylic and sulfonic acids were investigated. A set of 1195 zero- to three
      dimensional descriptors representing various structural characteristics was
      calculated for each molecule in the dataset. Classification and regression trees
      were successfully used as a descriptor selection method. Four descriptors were
      selected and used as inputs for adaptive neuro-fuzzy inference system. The root
      mean square errors for the calibration and prediction sets are 1.61 and 2.27,
      respectively, compared with 3.60 and 3.93, obtained from a previous mechanistic
      model.

PMID- 18064596
TI  - Quantification of carbonylated proteins in rat skeletal muscle mitochondria using
      capillary sieving electrophoresis with laser-induced fluorescence detection.
AB  - Carbonyl-modified proteins are markers of oxidative damage. Here, we report a new
      method for detecting and quantifying carbonylated proteins by capillary sieving
      electrophoresis (CSE) with LIF detection (CSE-LIF). Alexa 488 hydrazide is used
      for the specific labeling of carbonyls while 3-(2-furoyl) quinoline-2
      carboxaldehyde (FQ) is used for protein labeling. BSA subjected to metal
      catalyzed oxidation is used to optimize the labeling reactions, confirm the
      separation power of CSE, and characterize the response of the LIF detector. The
      method is capable of detecting femtomole (fmol) amounts of carbonyls in proteins
      with molecular masses ranging from 26 to 30 kDa. Using this method, we determined
      that mitochondrial proteins isolated from skeletal muscle contains 2.1 +/- 0.1
      (average +/- SD; n = 3) nmol carbonyl/mg protein. The methodology described here
      should be compatible with the analysis of single cells and needle biopsies taken
      from oxidative stress animal models.

PMID- 18064597
TI  - A polymerase chain reaction-restriction fragment length polymorphism method based
      on the analysis of a 16S rRNA/tRNA(Val) mitochondrial region for species
      identification of commercial penaeid shrimps (Crustacea: Decapoda: Penaeoidea) of
      food interest.
AB  - A simple PCR-RFLP method has been developed for the identification of 19 penaeid
      shrimp species of food interest belonging to the superfamily Penaeoidea.
      Preliminary amplification, sequencing and alignment of a 960 bp fragment of the
      16S rRNA/tRNA(Val)/12S rRNA mitochondrial region allowed the design of
      16Scru4/16Scru4 primers, constructed on well-conserved mitochondrial sequences of
      the penaeid shrimp species considered. Such primers afforded the amplification of
      an internal 515-535 bp region of the 16S rRNA/tRNA(Val) genes that, when
      subjected to cleavage with AluI, TaqI and HinfI, provided species-specific
      restriction patterns. Moreover, the proposed method also allowed the definition
      of different intraspecific restriction types between different populations of
      Litopenaeus vannamei, Farfantepenaeus notialis, Fenneropenaeus merguiensis,
      Metapenaeus sp., Melicertus latisulcatus and Pleoticus muelleri of different
      origins. The method described here was also successfully applied for the
      identification of penaeid shrimps in complex processed precooked foods, where
      this type of shellfish is used as an added-value food ingredient. Sequencing
      analysis provided new information about the genetic relationships among shrimps
      not only at the levels of species and genus, but also among different populations
      at intraspecific level. The 16S rRNA/tRNA(Val) fragment considered in this study
      seems to be accurate for shrimp species identification in raw and processed
      foodstuffs and for phylogenetic analysis among penaeid shrimp species.

PMID- 18064598
TI  - Electrophoretic field gradient focusing: an investigation of the experimental
      parameters.
AB  - Electrophoretic field gradient focusing has been used to separate the two
      oxidation states of myoglobin (Mb), and to separate Mb from bromophenol blue
      (BPB). Polyacrylamide and Sephadex were shown to be suitable packing materials
      whilst silica led to band broadening with Mb. BPB and Mb could be simultaneously
      focused apart using either a fixed 21-electrode setup or a dynamic 6-electrode
      setup. Using a dynamic three-electrode setup either analyte could be focused but
      not both simultaneously. It was shown that a higher ionic strength buffer in the
      separation channel compared to the coolant channel enhanced focusing between
      electrodes due to a conductivity gradient. Different running buffers were
      investigated and it was found that using a pH 8.6 buffer containing N,N,N
      tris(hydroxymethyl)aminomethane (Tris) and phosphate ions the oxidation states of
      Mb could be separated but the separation of Mb from BPB was not as good as would
      be hoped for. Using a pH 8.6 buffer containing Tris, N-2-hydroxyethylpiperazine
      N'-3-propanesulphonate and chloride ions as running buffer, BPB and Mb could be
      well separated but the two oxidation states of Mb merged.

PMID- 18064599
TI  - Mechanism of extracellular ubiquitination in the mammalian epididymis.
AB  - Posttranslational modification by ubiquitination marks defective or outlived
      intracellular proteins for proteolytic degradation by the 26S proteasome. The ATP
      dependent, covalent ligation and formation of polyubiquitin chains on substrate
      proteins requires the presence and activity of a set of ubiquitin activating and
      conjugating enzymes. While protein ubiquitination typically occurs in the cell
      cytosol or nucleus, defective mammalian spermatozoa become ubiquitinated on their
      surface during post-testicular sperm maturation in the epididymis, suggesting an
      active molecular mechanism for sperm quality control. Consequently, we
      hypothesized that the bioactive constituents of ubiquitin-proteasome pathway were
      secreted in the mammalian epididymal fluid (EF) and capable of ubiquitinating
      extrinsic substrates. Western blotting indeed detected the presence of the
      ubiquitin-activating enzyme E1 and presumed E1-ubiquitin thiol-ester
      intermediates, ubiquitin-carrier enzyme E2 and presumed E2-ubiquitin thiol-ester
      intermediates and the ubiquitin C-terminal hydrolase PGP 9.5/UCHL1 in the
      isolated bovine EF. Thiol-ester assays utilizing recombinant ubiquitin-activating
      and ubiquitin-conjugating enzymes, biotinylated substrates, and isolated bovine
      EF confirmed the activity of the ubiquitin activating and conjugating enzymes
      within EF. Ubiquitinated proteins were found to be enriched in the defective bull
      sperm fraction and appropriate proteasomal deubiquitinating and proteolytic
      activities were measured in the isolated EF by specific fluorescent substrates.
      The apocrine secretion of cytosolic proteins was visualized in transgenic mice
      and rats expressing the enhanced green fluorescent protein (eGFP) under the
      direction of ubiquitin-C promoter. Accumulation of eGFP, ubiquitin and
      proteasomes was detected in the apical blebs, the apocrine secretion sites of the
      caput epididymal epithelia of both the rat and mouse epididymal epithelium,
      although region-specific differences exist. Secretion of eGFP and proteasomes
      continued during the prolonged culture of the isolated rat epididymal epithelial
      cells in vitro. This study provides evidence that the activity of the ubiquitin
      system is not limited to the intracellular environment, contributing to a greater
      understanding of the sperm maturation process during epididymal passage.

PMID- 18064600
TI  - Electromagnetic millimeter wave induced hypoalgesia: frequency dependence and
      involvement of endogenous opioids.
AB  - Millimeter wave treatment (MMWT) is based on the systemic biological effects that
      develop following local skin exposure to low power electromagnetic waves in the
      millimeter range. In the present set of experiments, the hypoalgesic effect of
      this treatment was analyzed in mice. The murine nose area was exposed to MMW of
      "therapeutic" frequencies: 42.25, 53.57, and 61.22 GHz. MMWT-induced hypoalgesia
      was shown to be frequency dependent in two experimental models: (1) the cold
      water tail-flick test (chronic non-neuropathic pain), and (2) the wire surface
      test (chronic neuropathic pain following unilateral constriction injury to the
      sciatic nerve). Maximum hypoalgesic effect was obtained when the frequency was
      61.22 GHz. Other exposure parameters were: incident power density = 13.3
      mW/cm(2), duration of each exposure = 15 min. Involvement of delta and kappa
      endogenous opioids in the MMWT-induced hypoalgesia was demonstrated using
      selective blockers of delta- and kappa-opioid receptors and the direct ELISA
      measurement of endogenous opioids in CNS tissue. Possible mechanisms of the
      effect and the perspectives of the clinical application of MMWT are discussed.

PMID- 18064602
TI  - FGF-21/FGF-21 receptor interaction and activation is determined by betaKlotho.
AB  - Fibroblast growth factor-21 (FGF-21) is a metabolic regulator that can influence
      glucose and lipid control in diabetic rodents and primates. We demonstrate that
      betaKlotho is an integral part of an activated FGF-21-betaKlotho-FGF receptor
      (FGFR) complex thus a critical subunit of the FGF-21 receptor. Cells lacking
      betaKlotho did not respond to FGF-21; the introduction of betaKlotho to these
      cells conferred FGF-21-responsiveness and recapitulated the entire scope of FGF
      21 signaling observed in naturally responsive cells. Interestingly, FGF-21
      mediated effects are heparin independent suggesting that betaKlotho plays a role
      in FGF-21 activity similar to the one played by heparin in the signaling of
      conventional FGFs. Moreover, in addition to conferring specificity for FGF-21,
      betaKlotho appears to support FGF-19 activity and mediates the receptor
      selectivity profile of FGF-19. All together, these results indicate that
      betaKlotho and FGFRs form the cognate FGF-21 receptor complex, mediating FGF-21
      cellular specificity and physiological effects.

PMID- 18064603
TI  - Effect of Lepidium sativum L. on renal glucose reabsorption and urinary TGF-beta
      1 levels in diabetic rats.
AB  - The purpose of this study was to determine the mechanism underlying the
      hypoglycaemic activity of the aqueous extract perfusion of Lepidium sativum L.
      (LS) in normal and streptozotocin-induced diabetic rats. The aqueous LS extract
      was administered intravenously and the blood glucose levels were determined
      within 4 h of treatment. Plasma insulin concentrations and glycosuria were
      determined. The 24 h urinary transforming growth factor-beta1 (ELISA) was
      evaluated in diabetic and control rats 15 days after oral treatment with the
      aqueous LS extract at a dose of 20 mg/kg. The study showed that LS at a dose of
      10 mg/kg/h reduced blood glucose levels both in normal and diabetic rats (p <
      0.001). At the same time as a potent increase of glycosuria was observed both in
      normal and diabetic rats (p < 0.001). In addition, oral administration of LS for
      15 days normalized glycaemia (p < 0.001), enhanced glycosuria (p < 0.05 vs
      diabetic control) and decreased the amount of urinary TGF-beta1 (p < 0.01) in
      diabetic rats. It is concluded that the aqueous LS extract caused a potent
      inhibition of renal glucose reabsorption which in turn reduced blood sugar. This
      renal effect is at least one mechanism explaining the observed hypoglycaemic
      activity of this plant in normal and diabetic rats.

PMID- 18064604
TI  - Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage
      potential.
AB  - When mature adipocytes are subjected to an in vitro dedifferentiation strategy
      referred to as ceiling culture, these mature adipocytes can revert to a more
      primitive phenotype and gain cell proliferative ability. We refer to these cells
      as dedifferentiated fat (DFAT) cells. In the present study, we examined the
      multilineage differentiation potential of DFAT cells. DFAT cells obtained from
      adipose tissues of 18 donors exhibited a fibroblast-like morphology and sustained
      high proliferative activity. Flow cytometric analysis revealed that DFAT cells
      comprised a highly homogeneous cell population compared with that of adipose
      derived stem/stromal cells (ASCs), although the cell-surface antigen profile of
      DFAT cells was very similar to that of ASCs. DFAT cells lost expression of mature
      adipocytes marker genes but retained or gained expression of mesenchymal lineage
      committed marker genes such as peroxisome proliferator-activated receptor gamma
      (PPARgamma), RUNX2, and SOX9. In vitro differentiation analysis revealed that
      DFAT cells could differentiate into adipocytes, chondrocytes, and osteoblasts
      under appropriate culture conditions. DFAT cells also formed osteoid matrix when
      implanted subcutaneously into nude mice. In addition, clonally expanded porcine
      DFAT cells showed the ability to differentiate into multiple mesenchymal cell
      lineages. These results indicate that DFAT cells represent a type of multipotent
      progenitor cell. The accessibility and ease of culture of DFAT cells support
      their potential application for cell-based therapies.

PMID- 18064605
TI  - Deoxycholyltaurine rescues human colon cancer cells from apoptosis by activating
      EGFR-dependent PI3K/Akt signaling.
AB  - Recent studies indicate that secondary bile acids promote colon cancer cell
      proliferation but their role in maintaining cell survival has not been explored.
      We found that deoxycholyltaurine (DCT) markedly attenuated both unstimulated and
      TNF-alpha-stimulated programmed cell death in colon cancer cells by a
      phosphatidylinositol 3-kinase (PI3K)-dependent mechanism. To examine the role of
      bile acids and PI3K signaling in maintaining colon cancer cell survival, we
      explored the role of signaling downstream of bile acid-induced activation of the
      epidermal growth factor receptor (EGFR) in regulating both apoptosis and
      proliferation of HT-29 and H508 human colon cancer cells. DCT caused dose- and
      time-dependent Akt (Ser(473)) phosphorylation, a commonly used marker of
      activated PI3K/Akt signaling. Both EGFR kinase and PI3K inhibitors attenuated DCT
      induced Akt phosphorylation and Akt activation, as demonstrated by reduced
      phosphorylation of a GSK-3-paramyosin substrate. Transfection of HT-29 cells with
      kinase-dead EGFR (K721M) reduced DCT-induced Akt phosphorylation. In HT-29 cells,
      EGFR and PI3K inhibitors as well as transfection with dominant negative AKT
      attenuated DCT-induced cell proliferation. DCT-induced PI3K/Akt activation
      resulted in downstream phosphorylation of GSK-3 (Ser(21/9)) and BAD (Ser(136)),
      and nuclear translocation (activation) of NF-kappaB, thereby confirming that DCT
      induced activation of PI3K/Akt signaling regulates both proproliferative and
      prosurvival signals. Collectively, these results indicate that DCT-induced
      activation of post-EGFR PI3K/Akt signaling stimulates both colon cancer cell
      survival and proliferation.

PMID- 18064607
TI  - Lipocalin 2-mediated growth suppression is evident in human erythroid and
      monocyte/macrophage lineage cells.
AB  - Lipocalin 2 (LCN2), a secreted protein of the lipocalin family, induces apoptosis
      in some types of cells and inhibits bacterial growth by sequestration of the iron
      laden bacterial siderophore. We have recently reported that LCN2 inhibits the
      production of red blood cells in the mouse. Here we analyzed the role of LCN2 in
      human hematopoiesis. Expression of LCN2 was observed not only in mature cells
      such as those of the granulocyte/macrophage and erythroid lineages but also in
      hematopoietic stem/progenitor cells. We also examined expression of two candidate
      receptors for LCN2, brain type organic cation transporter (BOCT) and megalin, in
      various cell types. BOCT showed relatively high levels of expression in erythroid
      and hematopoietic stem/progenitor cells but lower levels in
      granulocyte/macrophage and T lymphoid cells. Megalin was expressed at high levels
      in T lymphoid and erythroid cells but at lower levels in granulocyte/macrophage
      lineage cells. LCN2 suppressed the growth of erythroid and monocyte/macrophage
      lineages in vitro, but did not have this effect on cells of other lineages. In
      addition, immature hematopoietic stem/progenitor cells were not sensitive to
      LCN2. These results demonstrate a lineage-specific role for LCN2 in human
      hematopoiesis that is reminiscent of its effects upon mouse hematopoiesis and
      strongly suggest an important in vivo function of LCN2 in the regulation of human
      hematopoiesis.

PMID- 18064606
TI  - High D-glucose reduces SLC29A1 promoter activity and adenosine transport
      involving specific protein 1 in human umbilical vein endothelium.
AB  - High D-glucose reduces human equilibrative nucleoside transporter 1 (hENT1)
      mediated adenosine uptake involving endothelial nitric oxide synthase (eNOS),
      mitogen-activated protein (MAP) kinase kinases 1 and 2/MAP kinases p42/44
      (MEK/ERKs), and protein kinase C (PKC) activation in human umbilical vein
      endothelium (HUVEC). Since NO represses SLC29A1 gene (hENT1) promoter activity we
      studied whether D-glucose-reduced hENT1-adenosine transport results from lower
      SLC29A1 expression in HUVEC primary cultures. HUVEC incubation (24 h) with high D
      glucose (25 mM) reduced hENT1-adenosine transport and pGL3-hENT1(-1114) construct
      SLC29A1 reporter activity compared with normal D-glucose (5 mM). High D-glucose
      also reduced pGL3-hENT1(-1114) reporter activity compared with cells transfected
      with pGL3-hENT1(-795) construct. N(G)-nitro-L-arginine methyl ester (L-NAME, NOS
      inhibitor), PD-98059 (MEK1/2 inhibitor), and/or calphostin C (PKC inhibitor)
      blocked D-glucose effects. Insulin (1 nM) and phorbol 12-myristate 13-acetate
      (PMA, 100 nM, PKC activator), but not 4alpha-phorbol 12,13-didecanoate
      (4alphaPDD, 100 nM, PMA less active analogue) reduced hENT1-adenosine transport.
      L-NAME and PD-98059 blocked insulin effects. L-NAME, PD-98059, and calphostin C
      increased hENT1 expression without altering protein or mRNA stability. High D
      glucose increased Sp1 transcription factor protein abundance and binding to
      SLC29A1 promoter, phenomena blocked by L-NAME, PD-98059, and calphostin C. Sp1
      overexpression reduced SLC29A1 promoter activity in normal D-glucose, an effect
      reversed by L-NAME and further reduced by S-nitroso-N-acetyl-L,D-penicillamine
      (SNAP, NO donor) in high D-glucose. Thus, reduced hENT1-mediated adenosine
      transport in high D-glucose may result from increased Sp1 binding to SLC29A1
      promoter down-regulating hENT1 expression. This phenomenon depends on eNOS,
      MEK/ERKs, and PKC activity, suggesting potential roles for these molecules in
      hyperglycemia-associated endothelial dysfunction.

PMID- 18064608
TI  - An in vitro recombination method to convert restriction- and ligation-independent
      expression vectors.
AB  - In recent years, restriction-less recombination cloning systems based on site
      specific recombinase with high efficiency have been proven to be very successful.
      Thus, it is desirable to convert existing conventional vectors to recombination
      vectors. In this report, we describe the conversion of a set of widely used
      conventional vectors to Gateway recombination expression vectors. An attB
      cassette flanked by several restriction enzyme sites was inserted in a cloning
      vector, and then subcloned into existing vectors to be converted to construct
      intermediate vectors containing the attB cassette, which were then converted to
      recombination expression vectors by in vitro recombination. The intermediate
      vectors generated in this study can be used for releasing the attB cassette to
      convert other vectors using the same protocol described here. With the increasing
      number of recombination vectors constructed with this protocol, the likeliness of
      releasing the attB cassette from an existing vector, rather than synthesizing it
      with PCR, will increase. The final expression vectors can also be used for
      releasing the attR cassette for constructing new vectors.

PMID- 18064609
TI  - Process analysis of macrotetrolide biosynthesis during fermentation by means of
      direct infusion LC-MS.
AB  - The optimization of the biosynthetic pathways is highly attractive for the large
      scale preparation of macrotetrolides, because overall yields in the chemical
      synthesis of compounds like nonactin have been very low. A key success factor
      determining the outcome of such optimizations is the adequate process analysis
      for the envisioned product. The analytical methods for process control involved
      in the past spectrophotometric and chromatographic measurements. LC-MS offers a
      modern approach to obtain more detailed data than the spectrophotometric and
      chromatographic measurements used in the past. In this work, a fast and versatile
      analytical LC-MS method has been set up, which has proven of much value for the
      in-process analysis of macrotetrolides during fermentation and which has allowed
      rapid large-scale bioprocess development.

PMID- 18064610
TI  - Analytical approach for the extraction of recombinant membrane viral glycoprotein
      from stably transfected Drosophila melanogaster cells.
AB  - Parameters for storage, lysis and concentration of Drosophila melanogaster
      Schneider 2 (S2AcRVGP) cells expressing the recombinant rabies virus glycoprotein
      (RVGP) were studied with regard to RVGP quantification by ELISA, for productivity
      evaluation and future purification. Lysis buffers were formulated with Tris,
      NaCl, glycerol, EDTA, KCl, Na(2)PO(4), MgCl(2), PMSF and NP-40 or CHAPS. S2AcRVGP
      cells (10(7) cells at the exponential growth phase) were frozen at -20 degrees C
      as a dry pellet, suspended in buffer (B) formulations or after treatment with
      lysis buffer (LB) formulations. They were then thawed as cell pellets or with B
      formulations or PBS at 4 degrees C or at room temperature and then lysed with LB
      formulations. For RVGP quantification by ELISA, a protocol was chosen of cell
      preparation including cell freezing as dry pellet, cell thawing at 4 degrees C
      with B4 (Tris, NaCl, MgCl(2), PMSF) and cell lysis with the LB4 (B4 + NP-40)
      since it fulfilled requirements of high RVGP detection, and was easily performed
      with mixtures freezing quickly, and a cost-saving LB formulation could be used.
      Using these established conditions, we examined the optimal cell concentration
      for RVGP quantification by ELISA. Results showed that an increase in the RVGP
      detection (from 62.5 to 1083 ng/10(7) cells) paralleled a decrease in the cell
      number (3 x 10(7) - 10(5) cells) used. The NP-40 concentration present in the LB4
      was further investigated as a function of the cell number used for sample
      preparation. Previous results were confirmed indicating that higher NP-40
      concentrations led to a decreased detection of RVGP. Altogether our data clearly
      pointed out the crucial effects of cell freeze, thaw, lysis and concentration on
      immune detection of recombinant membrane glycoproteins and can be useful as a
      guideline for sample preparation for this purpose.

PMID- 18064611
TI  - Protoplast isolation and transient gene expression in switchgrass, Panicum
      virgatum L.
AB  - Transient assay systems using protoplasts have been utilized in several plant
      species and are a powerful tool for rapid functional gene analysis and
      biochemical manipulations. A protoplast system has not been used in switchgrass
      (Panicum virgatum L.), even though it is a bioenergy crop that has received
      considerable attention. Here we report the first protocol to isolate large
      numbers of viable protoplasts from both leaves and roots of two switchgrass
      genotypes. Furthermore, we demonstrate transient expression of PEG-mediated DNA
      uptake in the isolated protoplasts by measuring the activity of beta
      glucuronidase (GUS) reporter gene driven by either the Cauliflower mosaic virus
      (CaMV) 35S promoter or the maize ubiquitin 1 promoter. Protoplast transformation
      with either the 35S or the ubiquitin promoter resulted in an increase in GUS
      activity compared to the untransformed controls; however, the extent of GUS
      activity was considerably higher for the ubiquitin promoter than for the 35S
      promoter. Collectively, our results indicate an efficient protoplast isolation
      and transient assay system that can be used to facilitate gene expression studies
      in switchgrass.

PMID- 18064612
TI  - The changing pattern of "smart" flow cytometry (S-FC) to assist the cost
      effective diagnosis of HIV, tuberculosis, and leukemias in resource-restricted
      conditions.
AB  - There is a need to introduce cytometry into areas of the globe that have remained
      virtually untouched by modern laboratory medicine. With the demand to carry out
      tests on 100,000 s of individuals requiring antiretroviral therapy (ART), flow
      cytometry must remain simple and cost-effective - while being sustainable and
      industry supported as well as proven by quality assessment (QA). This outlook is
      referred to as "smart flow cytometry" (S-FC). There are five main areas where the
      power of S-FC is demonstrated. These are: (i) the use of CD45 to assist precise
      cell counting in blood and tissue samples; (ii) the primary CD4 gating to count
      CD4+ T cells in patients waiting for ART, including the combination (i) and (ii)
      in the panleucogating (PLG) protocol; (iii) monitoring of human immunodeficiency
      virus (HIV+) patients during ART by the decreasing levels of lymphocyte
      activation in a CD8/CD38 test - leading to economies of viral-load assays; (iv)
      in tuberculosis and HIV-TB coinfections the use of TB-antigen-stimulated cytokine
      synthetic CD4+ T cells to identify active disease; and (v) the utilization of
      "minimal residual disease (MRD)-Lite" technology in patients 19 days after the
      start of antileukemic therapy to detect MRD. These methods of S-FC have been
      successfully introduced in "resource-restricted" countries with international and
      local QA.

PMID- 18064613
TI  - Thermodynamically favored aldol reaction of propargyl or allenyl esters:
      regioselective synthesis of carbinol allenoates.

PMID- 18064614
TI  - Higher gas solubility in nanoliquids?

PMID- 18064615
TI  - Synthesis and characterization of photoswitchable fluorescent silica
      nanoparticles.
AB  - We have designed and synthesized a new functional (amino reactive) highly
      efficient fluorescent molecular switch (FMS) with a photochromic diarylethene and
      a rhodamine fluorescent dye. The reactive group in this FMS -N-hydroxysuccinimide
      ester- allows selective labeling of amino containing molecules or other
      materials. In ethanolic solutions, the compound displays a large fluorescent
      quantum yield of 52 % and a large fluorescence modulation ratio (94 %) between
      two states that may be interconverted with red and near-UV light. Silica
      nanoparticles incorporating the new FMS were prepared and characterized, and
      their spectroscopic and switching properties were also studied. The dye retained
      its properties after the incorporation into the silica, thereby allowing light
      induced reversible high modulation of the fluorescence signal of a single
      particle for up to 60 cycles, before undergoing irreversible photobleaching. Some
      applications of these particles in fluorescence microscopy are also demonstrated.
      In particular, subdiffraction images of nanoparticles were obtained, in the focal
      plane of a confocal microscope.

PMID- 18064616
TI  - Spontaneous formation of a tungsten trioxide sphere-in-shell superstructure by
      chemically induced self-transformation.

PMID- 18064617
TI  - Lessons learnt from assembling screening libraries for drug discovery for
      neglected diseases.
AB  - To enable the establishment of a drug discovery operation for neglected diseases,
      out of 2.3 million commercially available compounds 222 552 compounds were
      selected for an in silico library, 57 438 for a diverse general screening
      library, and 1 697 compounds for a focused kinase set. Compiling these libraries
      required a robust strategy for compound selection. Rules for unwanted groups were
      defined and selection criteria to enrich for lead-like compounds which facilitate
      straightforward structure-activity relationship exploration were established.
      Further, a literature and patent review was undertaken to extract key recognition
      elements of kinase inhibitors ("core fragments") to assemble a focused library
      for hit discovery for kinases. Computational and experimental characterisation of
      the general screening library revealed that the selected compounds 1) span a
      broad range of lead-like space, 2) show a high degree of structural integrity and
      purity, and 3) demonstrate appropriate solubility for the purposes of biochemical
      screening. The implications of this study for compound selection, especially in
      an academic environment with limited resources, are considered.

PMID- 18064618
TI  - Atovaquone-statine "double-drugs" with high antiplasmodial activity.

PMID- 18064619
TI  - Prediction of elution bandwidth for purine compounds by a retention model in
      reversed-phase HPLC with linear-gradient elution.
AB  - In reversed-phase liquid chromatography, the retention mechanism of solute has
      been studied under linearly programmed gradient mobile-phase conditions. The
      separation of a mixture of four purine compounds (purine, theobromine,
      theophylline, and caffeine) was considered as a practical case in two binary
      mobile phase systems, water/methanol and water/acetonitrile. The retention model
      which describes how the retention factor is related to the mobile-phase
      composition has been developed in various mathematical forms to predict the
      retention time in both linear and gradient elutions. For a pulse injection of
      sample, two important factors, the retention time and the bandwidth of solute,
      might be computable to predict the elution profiles estimated by the distribution
      function, such as the Gaussian distribution function. In this work, a prediction
      method based on the analogue of the retention model was proposed to calculate the
      bandwidth in linear gradient elutions. Band broadening was caused by the
      different migration velocities of the front and rear ends of the solute band in a
      chromatographic column. Therefore, the migration behaviors of the front and rear
      ends of the solute band were explained with the same retention model which had
      been used to predict the retention time of solute. For the well retained solutes,
      theophylline and caffeine, the predicted bandwidth and experimentally obtained
      bandwidth showed good agreement in both isocratic and gradient elutions.

PMID- 18064620
TI  - Separation and quantification of lignans in Phyllanthus species by a simple
      chiral densitometric method.
AB  - A sensitive, selective, and robust high-performance TLC (HPTLC) method using
      chiral TLC plates for qualitative and quantitative analysis of phyllanthin (A),
      hypophyllanthin (B), niranthin (C), and nirtetralin (D), the active lignans of
      Phyllanthus species, was developed and validated. The effectiveness and role of
      various stationary phases viz TLC silica gel 60F(254), HPTLC silica gel 60F(254),
      and chiral TLC plates in the quantitation were evaluated. A precoated chiral TLC
      plate was found suitable for the simultaneous analysis of four pharmacologically
      active lignans. For achieving good separation, the optimized mobile phase of n
      hexane/acetone/1,4-dioxane (9:1:0.5 by volume) was used (R(f) = 0.30, 0.36, 0.41,
      and 0.48 for compounds A, B, C, and D, respectively). A densitometric
      determination of the above compounds was carried out in reflection/absorption
      mode at 620 nm. Optimized chromatographic conditions provide well-separated
      compact bands for the tested lignans. The calibration curves were found linear in
      the concentration range of 100-500 ng/band. Recoveries of A-D were 99.98, 100.51,
      99.22, and 98.74%, respectively. The method was validated according to ICH
      guidelines. The method reported here is reproducible and applied for the
      quantitative analysis of the above lignans in the leaves of four Phyllanthus
      species, i. e., P. amarus, P. maderaspatensis, P. urinaria, and P. virgatus.

PMID- 18064621
TI  - Determination of gentisin, isogentisin, and amarogentin in Gentiana lutea L. by
      capillary electrophoresis.
AB  - A novel, fast, and simple capillary electrophoresis method has been developed for
      the analysis of gentisin, isogentisin, and amarogentin in roots of Gentiana lutea
      (yellow gentian), an herb traditionally used as gastric stimulant. Gentisin and
      isogentisin are xanthones showing potent inhibition of monoamine oxidase type A
      and B, amarogentin represents one of the bitter principles of Gentiana,
      responsible for its gastric-roborant effects. Optimal CE-separation conditions
      comprise a 100 mM sodium tetraborate buffer of pH 9.3, containing 10 mM beta
      cyclodextrin as additive; optimum temperature and applied voltage were found to
      be 30 degrees C and 25 kV, respectively. Direct diode array detection at 260 nm
      (gentisin, isogentisin) and 242 nm (amarogentin) was performed, and the required
      analysis time was only 11 min. The developed method was validated for linearity,
      sensitivity, precision, and accuracy, and utilized to assay several commercially
      available G. lutea samples. Quantitative data obtained with the developed CE
      method are compared with HPLC results, and the advantages of each approach are
      discussed.

PMID- 18064622
TI  - Coordination features of a hybrid scorpionate/phosphane ligand exemplified with
      Iridium.
AB  - Although the pentacoordinated complex [Ir{(allyl)B(CH(2)PPh(2))(pz)(2)}(cod)] (1;
      pz=pyrazolyl, cod=1,5-cyclooctadiene), isolated from the reaction of [{Ir(mu
      Cl)(cod)}(2)] with [Li(tmen)][B(allyl)(CH(2)PPh(2))- (pz)(2)] (tmen=N,N,N',N'
      tetramethylethane-1,2-diamine), shows behavior similar to that of the related
      hydridotris(pyrazolyl)borate complex, the carbonyl derivatives behave in a quite
      different way. On carbonylation of 1, the metal--metal-bonded complex
      [(Ir{(allyl)B(CH(2)PPh(2))(pz)(2)}CO)(2)(mu-CO)] (2) that results has a single
      ketonic carbonyl bridge. This bridging carbonyl is labile such that upon
      treatment of 2 with PMe(3) the pentacoordinated Ir(I) complex
      [Ir(CO){(pz)B(eta(2)-CH(2)CH=CH(2))(CH(2)PPh(2))(pz)}(PMe(3))] (3) was isolated.
      Complex 3 shows a unique fac coordination of the hybrid ligand with the allyl
      group eta(2)-bonded to the metal in the equatorial plane of a distorted trigonal
      bipyramid with one pyrazolate group remaining uncoordinated. This unusual feature
      can be rationalized on the basis of the electron-rich nature of the metal center.
      The related complex [Ir(CO){(pz)B(eta(2)
      CH(2)CH=CH(2))(CH(2)PPh(2))(pz)}(PPh(3))] (4) was found to exist in solution as a
      temperature-dependent equilibrium between the cis-pentacoordinated and trans
      square planar isomers with respect to the phosphorus donor atoms. Protonation of
      3 with different acids is selective at the iridium center and gives the cationic
      hydrides [Ir{(allyl)B(CH(2)PPh(2))(pz)(2)}(CO)H(PMe(3))]X (X=BF(4) (5), MeCO(2)
      (6), and Cl (7)). Complex 7 further reacts with HCl to generate the unexpected
      product [Ir(CO)Cl{(Hpz)B(CH(2)PPh(2))(pz)CH(2)CH(Me)}(PMe(3))]Cl (9;
      Hpz=protonated pyrazolyl group) formed by the insertion of the hydride into the
      Ir-(eta(2)-allyl) bond. In contrast, protonation of complex 4 with HCl stops at
      the hydrido complex [Ir{(allyl)B(CH(2)PPh(2))(pz)(2)}(CO)H(PPh(3))]Cl (8). X-ray
      diffraction studies carried out on complexes 2, 3, and 9 show the versatility of
      the hybrid scorpionate ligand in its coordination.

PMID- 18064623
TI  - A general method for constructing optically active supramolecular assemblies from
      intrinsically achiral water-insoluble free-base porphyrins.
AB  - We have developed a general method to construct optically active porphyrin
      supramolecular assemblies by using a simple air-water interfacial assembly
      process. The method involved the in situ diprotonation of the free-base
      porphyrins at the air-water interface and subsequent assembly under compression.
      We showed that two intrinsically achiral water-insoluble free-base porphyrin
      derivatives, 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine (H(2)OEP) and
      5,10,15,20-tetra-p-tolyl-21H,23H-porphine (H(2)TPPMe), could be diprotonated when
      spread onto a 2.4 M hydrochloric acid solution surface, and the Langmuir-Schaefer
      (LS) films fabricated from the subphase exhibited strong circular dichroism (CD)
      absorption, whereas those fabricated from pure Milli-Q water subphase did not.
      The experimental data suggested that the helical stacking of the achiral
      porphyrin building blocks was responsible for the supramolecular chirality of the
      assemblies. Interestingly, such a method was successfully applied to a series of
      other intrinsically achiral free-base porphyrins such as 5,10,15,20-tetrakis(4
      methoxyphenyl)-21H,23H-porphine (H(2)TPPOMe), 5,10,15,20-tetraphenyl-21H,23H
      porphine (H(2)TPP), 5,10,15,20-tetrakis(4-(allyloxy)phenyl)-21H,23H-porphine
      (H(2)TPPOA), and 5,10,15,20-tetrakis(3,5-dimethoxyphenyl)-21H,23H-porphine
      (H(2)TPPDOMe). A possible mechanism has been proposed. The method provides a
      facile way to obtain optically active porphyrin supramolecular assemblies by
      using intrinsically achiral water-insoluble free-base porphyrin derivatives.

PMID- 18064624
TI  - In an attempt to provide a user's guide to the galaxy of benzylidene,
      alkoxybenzylidene, and indenylidene ruthenium olefin metathesis catalysts.
AB  - The data reported in this paper demonstrate that great care must be taken when
      choosing an appropriate catalyst for a given metathesis reaction. First
      generation catalysts were found to be useful in the metathesis of sterically
      unhindered substrates. Second-generation catalysts (under optimised conditions)
      showed good to excellent activities toward sterically hindered and electron
      withdrawing group (EWG)-substituted alkenes that do not react using the first
      generation complexes. A strong temperature effect was noted on all of the
      reactions tested. Interestingly, attempts to force a reaction by increasing the
      catalyst loading were much less effective. Therefore, when possible, it is
      suggested that metathesis transformations should be carried out with a second
      generation catalyst at 70 degrees C in toluene. However, different second
      generation catalysts proved to be optimal for different applications and no
      single catalyst outperformed all others in all cases. Nevertheless, some
      empirical rules can be deduced from the model experiments, providing preliminary
      hints for the selection of the optimal catalysts.

PMID- 18064625
TI  - Regio- and stereoselective ring-opening reactions of epoxides with indoles and
      pyrroles in 2,2,2-trifluoroethanol.
AB  - Aliphatic and aromatic epoxides react regio- and stereoselectively with indoles
      and pyrroles in 2,2,2-trifluoroethanol without the use of a catalyst or any other
      additive. While aromatic epoxides are selectively attacked at the benzylic
      position, aliphatic epoxides react at the less-substituted position. Chiral
      epoxides react with >99 % ee (ee=enantiomeric excess).

PMID- 18064626
TI  - Infrared study of intercomponent interactions in a switchable hydrogen-bonded
      rotaxane.
AB  - The macrocycle in rotaxane 1 is preferentially hydrogen bonded to the succinamide
      station in the neutral form, but can be moved to the naphthalimide station by one
      electron reduction of the latter. The hydrogen bonding between the amide NH
      groups of the macrocycle and the C double bond O groups in the binding stations
      in the thread was studied with IR spectroscopy in different solvents in both
      states. In addition, the solvent effect on the vibrational frequencies was
      analyzed; a correlation with the solvent acceptor number (AN) was observed. The
      conformational switching upon reduction could be detected by monitoring the
      hydrogen-bond-induced shifts of the nu(CO) frequencies of the C double bond O
      groups of the succinamide and the reduced naphthalimide stations. The macrocycle
      was found to shield the encapsulated station from the solvent: wavenumbers of
      nu(CO) bands of the C double bond O groups residing inside the macrocycle cavity
      remain unaffected by the solvent polarity.

PMID- 18064627
TI  - Skeletal muscle cells express the profibrotic cytokine connective tissue growth
      factor (CTGF/CCN2), which induces their dedifferentiation.
AB  - Fibrotic disorders are typified by excessive connective tissue and extracellular
      matrix (ECM) deposition that precludes normal healing processes of different
      tissues. Connective tissue growth factor (CTGF) seems to be involved in the
      fibrotic response. Several muscular dystrophies are characterized by a
      progressive weakness and wasting of the musculature, and by extensive fibrosis.
      However, the exact role of CTGF in skeletal muscle is unknown. Here we show that
      myoblasts and myotubes are able to synthesize CTGF in response to transforming
      growth factor type-beta (TGF-beta) and lysophosphatidic acid (LPA). CTGF induced
      several ECM constituents such as fibronectin, collagen type I and alpha4, 5, 6,
      and beta1 integrin subunits in myoblasts and myotubes. CTGF had an important
      inhibitory effect on muscle differentiation evaluated by the decrease in the
      nuclear translocation of the early muscle regulatory factor myogenin and myosin.
      Remarkable, CTGF treatment of myoblasts induced their dedifferentiation,
      characterized by down regulating MyoD and desmin, two markers of committed
      myoblasts, together with a strong reorganization of cytoskeletal filaments. These
      results provide novel evidence for the underlying mechanisms and participation of
      skeletal muscle cells in the synthesis and role of CTGF inducing fibrosis,
      inhibiting myogenesis and dedifferentiating myoblasts.

PMID- 18064629
TI  - All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation
      of aquaporin-3 and water permeability in human keratinocytes.
AB  - One of the major characteristics of human skin photoaging induced by ultraviolet
      (UV) radiation is the dehydration of the skin. Water movement across plasma
      membrane occurs via diffusion through lipid bilayer and via aquaporins (AQPs). We
      find that UV induces aquaporin-3 (AQP3) down-regulation in human skin
      keratinocytes. MEK/ERK inhibitors PD98059 and U0126 inhibit UV-induced down
      regulation of AQP3. Antioxidant N-acetyl-L-cysteine or NAC blocks UV-induced
      MEK/ERK activation and down-regulation of AQP3. All-trans retinoic acid or atRA,
      while alone inducing AQP3 expression, attenuates UV-induced down-regulation of
      AQP3 and water permeability. Using special inhibitors, we find that activation of
      EGFR and inhibition on ERK activation are involved in atRA's protective effects
      against UV-induced AQP3 down-regulation. Using specific AQP3's water transport
      inhibitors and siRNA knockdown, we observe that AQP3 is involved in cell
      migration and in vitro wound healing. UV-induced AQP3 down-regulation results in
      reduced water permeability, decreased cell migration, and delayed wound healing,
      which are attenuated by atRA pretreatment. We conclude that atRA protects against
      UV-induced down-regulation AQP3 and decrease in water permeability, reduction in
      cell migration and delayed in vitro wound healing via trans-activation of EGFR
      and inhibition on ROS-mediated MEK/ERK pathway. This novel finding provides
      evidence to support possible involvement of AQP3 in UV induced skin dehydration.

PMID- 18064628
TI  - Regulation of bim in glucocorticoid-mediated osteoblast apoptosis.
AB  - Osteoblasts undergo apoptosis both in vitro and in vivo in response to high dose
      glucocorticoid (GC) treatment. However, the molecular mechanisms remain elusive,
      hindering the prevention and treatment of this side-effect. Apoptosis was induced
      by dexamethasone (Dex) in murine MBA-15.4 osteoblasts within 24-48 h of
      treatment. We found dose- and time-dependent upregulation of Bim protein, a pro
      apoptotic Bcl-2 family member, with highest levels at 24-48 h for 1 microM Dex.
      This was also observed in primary human bone marrow stromal cells. Bim is
      subjected to stringent transcriptional and post-translational regulation in
      osteoblasts. Bim mRNA was upregulated in response to 1 microM Dex; both
      cycloheximide and the GC receptor antagonist, RU486, prevented Dex-induction of
      Bim protein, indicating transcriptional regulation involving the GC receptor. The
      proteasome inhibitor, MG132, potently increased Bim protein levels. Bim was also
      upregulated in osteoblasts undergoing apoptosis in response to serum deprivation
      and matrix detachment. Gene silencing experiments show that short interference
      RNA (siRNA) specific for Bim or the downstream effector Bax both reduced
      apoptosis induced by Dex in osteoblastic cells. These findings suggest that Bim
      is a novel regulator of osteoblast apoptosis and may be a therapeutic target.

PMID- 18064630
TI  - Differential regulation of the lateral mobility of plasma membrane phospholipids
      by the extracellular matrix and cholesterol.
AB  - In this study, we compared qualitative and quantitative changes in the lateral
      mobility of phospholipid molecules in the plasma membrane of intact cells under
      various conditions of specific interaction of integrins in the cell membrane with
      two extracellular matrix (ECM) components viz. fibronectin (FN) and laminin (LN).
      We found a strong and specific correlation between the lower lateral mobility of
      phosphatidylcholine (PC) and higher lateral mobility of phosphatidylethanolamine
      (PE) when cells were expressing high levels of alpha5beta1 integrin and thus were
      adherent and motile on FN. The interaction between PC and FN in alpha5 integrin
      expressing cells was aided by the strong affinity of alpha5 integrin to the FN
      matrix. Cholesterol was involved in regulating the lateral mobility of PC to a
      great extent and of PE to a lesser extent without affecting the overall
      microviscosity of the plasma membrane or the distribution of caveolin-marked
      domains. The distribution and mobility of PC and PE molecules in the
      lamellipodial regions differed from that in the rest of the membrane and also in
      the more motile and in the less motile cells. We propose that these differences
      in distribution of PC and PE in different regions of cell membrane and their
      respective lateral mobility are observed due to the specific interaction of PC
      molecules with FN molecules in the ECM. Our results outline a new role of
      integrin-matrix interactions in the regulation of membrane phospholipid behavior.

PMID- 18064631
TI  - Interleukin-18 stimulates fibronectin expression in primary human cardiac
      fibroblasts via PI3K-Akt-dependent NF-kappaB activation.
AB  - Fibronectin (FN), a key component of the extracellular matrix, is upregulated in
      cardiac tissue during myocardial hypertrophy and failure. Here we show that
      interleukin (IL)-18, a proinflammatory and pro-hypertrophic cytokine, stimulates
      FN expression in adult human cardiac fibroblasts (HCF), an effect blocked by
      either the IL-18BP:Fc chimera or IL-18 neutralizing antibodies. IL-18 stimulated
      FN promoter-reporter activity in HCF, a response attenuated by mutation of an NF
      kappaB binding site in the FN promoter. Overexpression of p65 stimulated FN
      transcription. IL-18 stimulated in vitro (p65, p50) and in vivo NF-kappaB DNA
      binding activities, and induced kappaB-dependent reporter gene activity. These
      effects were inhibited by adenoviral transduction of dominant negative (dn) p65
      (Ad.dnp65) and dnIKK2 (Ad.dnIKK2). Investigation of signaling intermediates
      revealed that IL-18 stimulated PI3 kinase activity (blocked by wortmannin,
      LY294002, or Ad.dnPI3Kp85), and Akt phosphorylation and kinase activity (blocked
      by SH-5 or Ad.dnAkt). Furthermore, targeting MyD88, IRAK1, TRAF6, PI3K, Akt, and
      NF-kappaB by RNA interference or dn expression vectors blunted IL-18 mediated FN
      transcription and mRNA expression. Conversely, FN stimulated IL-18 expression.
      These data provide the first evidence that IL-18 and FN stimulate each other's
      expression in HCF, and suggest a role for IL-18, FN and their crosstalk in
      myocardial hypertrophy and remodeling, disease states characterized by enhanced
      FN expression and fibrosis.

PMID- 18064632
TI  - GRP78 and Raf-1 cooperatively confer resistance to endoplasmic reticulum stress
      induced apoptosis.
AB  - The chaperone glucose-regulated protein, 78/immunoglobulin binding protein
      (GRP78/Bip), protects cells from cytotoxicity induced by DNA damage or
      endoplasmic reticulum (ER) stress. In this study, we showed that GRP78 is a major
      inducible protein in human non-small cell lung cancer H460 cells treated with ER
      stress inducers, including A23187 and thapsigargin. AEBSF, an inhibitor of serine
      protease, diminished GRP78 induction, enhanced mitochondrial permeability, and
      augmented apoptosis in H460 cells during ER stress. Simultaneously, AEBSF
      promoted Raf-1 degradation and suppressed phosphorylation of Raf-1 at Ser338
      and/or Tyr340 during ER stress. Coimmunoprecipitation assays and subcellular
      fractionations showed that GRP78 associated and colocalized with Raf-1 on the
      outer membrane of mitochondria, respectively. While treatment of cells with ER
      stress inducers inactivated BAD by phosphorylation at Ser75, a Raf-1
      phosphorylation site; AEBSF attenuated phosphorylation of BAD, leading to
      cytochrome c release from mitochondria. Additionally, overexpression of GRP78
      and/or Raf-1 protected cells from ER stress-induced apoptosis. Taken together,
      our results indicate that GRP78 may stabilize Raf-1 to maintain mitochondrial
      permeability and thus protect cells from ER stress-induced apoptosis.

PMID- 18064633
TI  - Macrophage migration inhibitory factor (MIF) is necessary for progression of
      autoimmune diabetes mellitus.
AB  - Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine of the
      innate immune system that plays a major role in the induction of
      immunoinflammatory responses. To examine the role of endogenous MIF in the
      pathogenesis of type 1 diabetes (TID) we evaluated the effects of administration
      of neutralizing anti-MIF antibodies to NOD mice with accelerated forms of
      diabetes induced by injection of cyclophosphamide or by transfer of diabetogenic
      spleen cells. Both accelerated forms of diabetes were markedly reduced by anti
      MIF antibody. Furthermore, MIF-deficient (MIF(-/-)) mice were less susceptible to
      the induction of immunoinflammatory diabetes, insulitis and apoptosis within the
      endocrine pancreas by multiple low doses of streptozotocin (MLD-STZ) than
      genetically matched wild type (WT) mice. MIF deficiency resulted in lower
      proliferation and lymphocyte adhesion, as well as reduced production from the
      spleens and peritoneal cells of a variety of inflammatory mediators typically
      associated with development of the disease including IL-12, IL-23, TNF-alpha, and
      IL-1beta. Furthermore, MIF deletion affected the production of IL-18, TNF-alpha,
      IL-1beta, and iNOS in the islets of Langerhans. These data, along with the higher
      expression of IL-4 and TGF-beta observed in the periphery and in the pancreas of
      MLD-STZ-challenged MIF(-/-) mice as compared to WT controls suggest that MIF
      deficiency has induced an immune deviation towards protective type 2/3 response.
      These results suggest that MIF participates in T1D by controlling the functional
      activity of monocytes/macrophages and T cells and modulating their secretory
      capacity of pro- and anti-inflammatory molecules.

PMID- 18064634
TI  - Two-scale, three-phase theory for swelling drug delivery systems. Part I:
      constitutive theory.
AB  - Polymeric carriers used in drug delivery applications, such as hydroxypropyl
      methylcellulose, that swell significantly upon coming in contact with water (or
      biological fluid) have been historically difficult to model due to the complex
      interplay of forces. This article seeks to introduce a thermodynamically
      consistent framework in which to address such problems. Here, a constitutive
      theory is developed that is applicable to viscoelastic polymers carrying an
      initially elastic drug that subsequently dissolves when exposed to a viscous
      fluid. The theoretical model consists of three phases, the polymer, drug, and
      fluid. A novel form of Darcy's law is reported that clearly distinguishes between
      distortional and dilatational forces and accounts for the affect of polymer
      relaxation on fluid transport. A standard form of Fick's law is also derived.

PMID- 18064635
TI  - A23187, ionomycin and thapsigargin upregulate mRNA of HIF-1alpha via endoplasmic
      reticulum stress rather than a rise in intracellular calcium.
AB  - Hypoxia inducible factor 1 (HIF-1) coordinates major responses to hypoxia, with
      the notion that its alpha subunit is degraded under normoxia but stable under
      hypoxia. Recently, calcium was shown to affect expression of HIF-1alpha. While
      lowering cytosolic calcium accumulates HIF-1alpha, a calcium increase by the
      ionophores A23187 or ionomycin as well as the endoplasmic reticulum (ER) Ca(2+)
      ATPase inhibitor thapsigargin produced inconsistent results with reports to
      either increase or decrease HIF-1alpha protein. In the human hepatocyte cell line
      HepG2 only A23187, but neither ionomycin nor thapsigargin, accumulated HIF-1alpha
      protein under normoxia. However, A23187 does so independently of a calcium
      increase. A23187 not only accumulated HIF-1alpha protein but also mRNA of HIF
      1alpha, with the notion that protein but not mRNA accumulation was attenuated by
      blocking mitogen-activated protein kinase (MAPK), suggesting that HIF-1alpha
      protein accumulation is not a direct consequence of its mRNA elevation. Indeed,
      protein stability determinations implied that A23187 enhanced translation of HIF
      1alpha. Interestingly, ionomycin and thapsigargin also increased the HIF-1alpha
      mRNA content. Although not increasing the HIF-1alpha protein amount under
      normoxia, both compounds enhanced protein accumulation of HIF-1alpha under
      hypoxia. Taking into account that induction of ER stress by tunicamycin and
      brefeldin A, without altering intracellular calcium concentrations, also
      increased HIF-1alpha mRNA, suggests that ER stress pathways enhanced
      transcription of HIF-1alpha mRNA. We conclude that ER stress rather than calcium
      fluctuations increased HIF-1alpha mRNA content by established calcium liberating
      agents, which alone is insufficient for normoxic HIF-1alpha accumulation.

PMID- 18064636
TI  - Examining the statistical properties of fine-scale mapping in large-scale
      association studies.
AB  - Interpretation of dense single nucleotide polymorphism (SNP) follow-up of genome
      wide association or linkage scan signals can be facilitated by establishing
      expectation for the behaviour of primary mapping signals upon fine-mapping, under
      both null and alternative hypotheses. We examined the inferences that can be made
      regarding the posterior probability of a real genetic effect and considered
      different disease-mapping strategies and prior probabilities of association. We
      investigated the impact of the extent of linkage disequilibrium between the
      disease SNP and the primary analysis signal and the extent to which the disease
      gene can be physically localised under these scenarios. We found that large
      increases in significance (>2 orders of magnitude) appear in the exclusive domain
      of genuine genetic effects, especially in the follow-up of genome-wide
      association scans or consensus regions from multiple linkage scans. Fine-mapping
      significant association signals that reside directly under linkage peaks yield
      little improvement in an already high posterior probability of a real effect.
      Following fine-mapping, those signals that increase in significance also
      demonstrate improved localisation. We found local linkage disequiliptium patterns
      around the primary analysis signal(s) and tagging efficacy of typed markers to
      play an important role in determining a suitable interval for fine-mapping. Our
      findings help inform the interpretation and design of dense SNP-mapping follow-up
      studies, thus facilitating discrimination between a genuine genetic effect and
      chance fluctuation (false positive).

PMID- 18064637
TI  - Assessment of protein nutritional status in children.
AB  - When considering the effects of disease on nutritional status it is useful to
      think of the body consisting of lean mass and fat mass. The latter relates to
      energy status and the former to protein nutritional status. In addition,
      childhood growth in length/height is to a high degree dependent upon having an
      adequate protein intake. If insufficient non-protein energy is fed, then protein
      is used to help meet energy needs. Hence achieving an optimum protein nutritional
      status also requires receiving sufficient energy. Assessment of protein
      nutritional status starts with measurement of length/height and weight in
      relationship to growth standards. Next comes using mid-upper arm parameters in
      which the measurement of muscle area or circumference is a reflection of protein
      nutritional status while triceps skin-fold thickness is a measurement of energy
      status. Serum albumin remains the number one short term parameter reflecting
      protein nutritional status followed by serum transferrin. Plasma amino acid
      profiles can be measured but are mostly dependent on recent dietary intake and so
      are hard to interpret. Classically, nitrogen balance has been used as a
      reflection of dietary protein intake. While it has been used extensively on a
      research basis its clinical applicability is limited.

PMID- 18064638
TI  - Childhood cancer and vitamins: prevention and treatment.
AB  - Discussions of pediatric nutrition and cancer usually focus on important issues
      of ensuring an adequate nutrient intake (enteral and parenteral) during and after
      the early treatment phase of care. However, information is available that
      suggests that vitamin status may have additional roles in the care of children
      with cancer. Over the last decade, investigators have reported findings that
      suggest that maternal preconception and perinatal vitamin intake and status
      influence the cancer risk of the infant and child. Others have shown a
      relationship between vitamin and antioxidant status and the prevalence and
      severity of adverse side effects for children undergoing chemotherapy. Vitamin D
      has potential anti-cancer activity and vitamin D status is suboptimal in many
      children in North America. Each of these issues is briefly presented from a
      perspective of prevention and treatment of childhood cancer.

PMID- 18064639
TI  - Children's Oncology Group (COG) Nutrition Committee.
AB  - The Children's Oncology Group (COG) Nutrition Committee was established to
      further the knowledge of nutrition in children with cancer by education and the
      conduct of clinical trials. A survey of COG institutions revealed lack of
      conformity in evaluation and categorization of nutritional status, and criteria
      for nutritional intervention. The Committee subsequently established specific
      categories of malnutrition (Underweight and Overweight) based on ideal body
      weight or body mass index. An algorithm was developed as a guideline for
      nutritional intervention as well as references and resources for determining
      estimated needs. The Committee embarked on concepts for clinical trials of
      nutritional interventions. The first pilot study, evaluating the feasibility of
      using an immunoneutraceutical precursor for glutathione production, has been
      completed. This study showed weight gain and improvement in glutathione status. A
      pilot trial of proactive enteral feeding for patients at high risk of
      malnutrition has commenced. The Committee believes that nutrition is relevant to
      all aspects of cancer control. The paucity of nutritional investigation in
      children with cancer needs to be rectified.

PMID- 18064640
TI  - Energy balance and its measurement in childhood disease.
AB  - Under and overweight, usually secondary to energy imbalance, are common
      complications of childhood chronic disease. A simple energy balance paradigm has
      been helpful in understanding the etiology of underweight and overweight in
      chronic disease, including malignant disease, particularly when measurements of
      total energy expenditure have been made using the doubly labeled water method.
      Measurements of energy intake are usually insufficiently accurate and precise to
      be informative, and measurements of energy expended at rest alone provide an
      incomplete and potentially misleading assessment of energy expenditure and the
      causes of energy imbalance. In some diseases, such as acute lymphoblastic
      leukemia, the natural history and etiology of energy imbalance are now
      particularly well understood. Recent improvements in our understanding of
      etiology should lead to improved strategies for the prevention and treatment of
      underweight and overweight in chronic disease. In some diseases, cachectic
      processes drive the development of underweight: these are partly independent of
      energy balance, and strategies for prevention and treatment may require
      approaches aimed at modifying the cachectic process rather than attempting to
      modify energy balance directly.

PMID- 18064641
TI  - Osteonecrosis in children and adolescents with cancer.
AB  - Osteonecrosis is recognized increasingly as a complication of the treatment of
      cancer in young people, especially those with acute lymphoblastic leukemia and
      non-Hodgkin lymphoma, reflecting a probable pathogenetic role of steroid therapy.
      Children >/=10 years of age and Whites are at particular risk, and genetic
      predispositions have been identified. The disorder affects weight-bearing joints
      predominantly. It is commonly bilateral and multi-articular. Treatment options
      include both surgical and non-surgical interventions.

PMID- 18064642
TI  - Assessment of nutritional status in children with acute lymphoblastic leukemia in
      Northern Mexico: A 5-year experience.
AB  - Nutritional status is an important variable when planning the treatment of
      children with acute lymphoblastic leukemia (ALL). We determined the nutritional
      status of children from Northern Mexico diagnosed with ALL during a 5-year period
      at a public university hospital. One hundred and two children were included.
      Evaluation by a clinical nutritionist through a food frequency questionnaire and
      anthropometrical measurements was carried out. Dual energy X-ray absorptiometry
      (DEXA) for body composition analysis was performed. Based on their body mass
      index (BMI) percentile, children were classified in four groups as underweight,
      normal weight, at-risk for overweight and overweight. Fifty-four patients were
      boys (53%) and 48 (47%) girls. Median values were: age, 6.0 years; weight, 23 kg,
      height, 118 cm. BMI median value was 16.7. In 78 patients studied by DEXA, median
      body mass was 24,335 g, with 66.4% from lean tissue, 23.5% from fat. Bone mineral
      content was 10.6%. Bone density was 0.754 g/cm(2). The majority of children with
      ALL in Northern Mexico are well nourished at diagnosis and have a normal body
      composition. Early nutritional intervention is important to maintain this status
      and correct specific abnormalities.

PMID- 18064643
TI  - Body composition, exercise and energy expenditure in survivors of acute
      lymphoblastic leukaemia.
AB  - Survivors of acute lymphoblastic leukaemia (ALL) are recognised to become
      overweight and this seems to worsen with increasing length of follow up.
      Increases in body fat appear to be more marked in girls than in boys and in those
      who have received prophylactic cranial irradiation. Physiological responses to
      exercise, both at submaximal and maximal levels, are different in ALL survivors
      compared to controls. Heart rate appears to be increased at low intensity
      exercise, possibly to maintain adequate cardiac output. Maximal aerobic capacity
      is reduced, signifying a lower level of physical fitness. Total daily energy
      expenditure (TDEE) under free living conditions appears limited due to low
      participation in physical activity. Associations exist between measures of energy
      expenditure and body fat, but whether these are cause or effect has yet to
      proven.

PMID- 18064644
TI  - Vitamin D status and bone biomarkers in childhood cancer.
AB  - Early detection of abnormalities in bone turnover may be facilitated by assessing
      biomarkers of bone metabolism including vitamin D status. In many children with
      cancer, biomarkers of bone formation (osteocalcin, bone specific alkaline
      phosphatase and carboxy-(or N terminal) propeptide of type 1 procollagen) were
      observed to be suppressed, while bone resorption was elevated as measured by
      serum cross-linked (or C-terminal) telopeptide of type 1 collagen. Insulin-like
      growth factor 1, which stimulates bone formation, may be suppressed indirectly
      indicating a growth hormone insufficiency. Leptin may also play a role in bone
      remodeling as hyperleptinemia has been observed in association with acute
      lymphoblastic leukemia. Evaluation of bone status using such biomarkers is
      complicated by the lack of universally accepted reference values and the
      variation by age, gender, or pubertal status. Etiologic factors contributing to
      the observed skeletal morbidities include disease process, chemotherapy (drugs
      such as glucocorticoids and methotrexate) and radiotherapy. Other factors common
      to children with cancer, such as chronic inflammation, dietary changes and
      physical inactivity, must also be taken into account. The current evidence for
      abnormalities in biomarkers of vitamin D status and bone turnover will be the
      focus of this review of published studies.

PMID- 18064645
TI  - Bringing evidence to complementary and alternative medicine in children with
      cancer: Focus on nutrition-related therapies.
AB  - Children with cancer frequently use complementary and alternative medicine (CAM),
      especially in conjunction with conventional therapy. Dietary supplements are a
      commonly used CAM modality, with the prevalence of supplement use ranging from
      35% to 50% of children with cancer in surveys completed in the United States.
      Less is known about the use of dietary supplements in developing countries. The
      evidence for some dietary supplements providing some benefit to children with
      cancer is reviewed. Preliminary studies have shown that antioxidant status may
      affect chemotherapy tolerance in children with acute lymphoblastic leukemia.
      Other supplements, including TRAUMEEL S, glutamine, vitamin E, Immunocal,
      colostrum, and probiotics, may help to reduce gastrointestinal toxicities of
      chemotherapy and radiation. However, more definitive evidence is needed. Most
      dietary supplements have not been tested adequately to determine their safety and
      efficacy, with even less understood about their potential interactions with
      conventional chemotherapy and radiation. With the greater use of dietary
      supplements by patients with cancer, increasing scientific attention is being
      paid to the investigation of these therapies. But research on dietary supplements
      is complex and usually more difficult than that on conventional medications.
      Strong research designs are critical in obtaining information that will
      ultimately influence clinical practice and public awareness.

PMID- 18064646
TI  - Height deficit during and many years after treatment for acute lymphoblastic
      leukemia in children: a review.
AB  - There are conflicting data on the incidence and severity of height deficits in
      children with acute lymphoblastic leukemia (ALL). This is probably due to: (1)
      collection of data in different phases of treatment; (2) differences in
      chemotherapeutic regimens; (3) inclusion or not of children who had received
      cranial irradiation (CRT); (4) limited numbers of patients; (5) relative numbers
      of prepubertal and pubertal children; (6) different ways of measuring growth
      deficits. Twenty-five papers published between 1987 and 2006 were reviewed. These
      reveal that (1) chemotherapy always causes some height reduction during treatment
      regardless of whether additional CRT is given; (2) catch-up growth occurs
      immediately after cessation of treatment; (3) intensive chemotherapy alone
      significantly decreases height in the long-term but to a lesser extent than with
      additional CRT; (4) young children develop more severe height loss; (5) girls are
      reported to have greater height deficits but confounding factors have not been
      adequately considered; (6) late growth hormone (GH) deficiency has been detected
      in many children, mostly in those who had CRT; (7) GH replacement therapy seems
      to be effective. ALL relapse in GH-treated children is not more common than in
      those not treated with GH.

PMID- 18064647
TI  - Ploidy and karyotype complexity are powerful prognostic indicators in the Ewing's
      sarcoma family of tumors: a study by the United Kingdom Cancer Cytogenetics and
      the Children's Cancer and Leukaemia Group.
AB  - Ewing's sarcoma family tumors (ESFT) are characterized by the presence of EWSR1
      ETS fusion genes. Secondary chromosome changes are frequently described, although
      their clinical significance is not clear. In this study, we have collected and
      reviewed abnormal karyotypes from 88 patients with primary ESFT and a
      rearrangement of 22q12. Secondary changes were identified in 80% (70/88) of
      tumors at diagnosis. Multivariate analysis showed a worse overall and relapse
      free survival (RFS) for those with a complex karyotype (overall survival, P =
      0.005; RFS, P = 0.04), independent of metastatic disease. Univariate survival
      analysis showed that a chromosome number above 50 or a complex karyotype was
      associated with a worse overall survival (>50 chromosomes, P = 0.05; complex
      karyotype, P = 0.04). There was no association between type of cytogenetic
      abnormality and the presence of metastatic disease at diagnosis. Univariate and
      multivariate survival analysis of a small subgroup with trisomy 20 indicated that
      trisomy 20 was associated with a worse overall and RFS. There was no difference
      in outcome associated with other recurrent trisomies (2, 5, 7, 8, or 12) or the
      common recurrent secondary structural rearrangements (deletions of 1p36, 9p12,
      17p13, and 16q, and gain of 1q), although numbers were small. These data
      demonstrate the continued value of cytogenetics as a genome-wide screen in ESFT
      and illustrates the potential importance of secondary chromosome changes for
      stratification of patients for risk. Specifically, karyotype complexity appears
      to be a powerful predictor of prognosis, and the presence of trisomy 20 may be a
      marker of a more aggressive subset of this group.

PMID- 18064648
TI  - SOS1 mutations are rare in human malignancies: implications for Noonan Syndrome
      patients.
AB  - Germ line gain-of-function mutations in several members of the RAS/ERK pathway,
      including PTPN11, KRAS, and RAF1, cause the autosomal dominant genetic disorder
      Noonan Syndrome (NS). NS patients are at increased risk of
      leukemia/myeloproliferative disease and possibly some solid tumors, such as
      neuroblastoma. Recently, SOS1 gain of function mutations have also been shown to
      cause NS. Somatic PTPN11, KRAS, and RAF1 mutations occur (although at different
      frequencies) in a variety of sporadic neoplasms, but whether SOS1 mutations are
      associated with human cancer has not been evaluated. We sequenced DNA from a
      total of 810 primary malignancies, including pancreatic, lung, breast, and colon
      carcinomas, and acute myelogenous leukemia, as well as several neuroblastoma cell
      lines. From this large, diverse series, missense SOS1 mutations were identified
      in a single pancreatic tumor, one lung adenocarcinoma, and a T-cell acute
      lymphoblastic leukemia cell line. Our findings suggest that SOS1 is not a
      significant human oncogene in most cancers. Furthermore, NS patients with SOS1
      mutations may not be at increased risk of developing cancer.

PMID- 18064649
TI  - The role of insulin receptor substrate-1 in transformation by v-src.
AB  - The insulin receptor substrate-1 (IRS-1), a docking protein for both the insulin
      (InR) and the insulin-like growth factor-1 (IGF-IR) receptors, sends a mitogenic,
      anti-differentiation and transforming signal. We now show that down-regulation of
      IRS-1 in cells transformed by v-src reverses the transformed phenotype (growth in
      serum-free medium and colony formation in soft agar). IRS-1 translocates to
      nuclei and is found in the cyclin D1 and rDNA promoters. Stat3, which is
      activated by src, requires both IRS-1 and src for promoter occupancy. IRS-1 (by
      itself or in combination with src) also markedly increases transcription from
      these two promoters. We also show that IRS-1 binds to src via its two PI3-K
      binding tyrosine residues, and that these two residues are required for
      transformation of mammary cancer cells expressing v-src. Taken together, these
      results indicate a significant role of IRS-1 in the activation of cell cycle
      progression genes and transformation of cells by v-src.

PMID- 18064652
TI  - Skeletal toxicities of treatment in children with cancer.
AB  - For many childhood cancer survivors, the future will hold years of pain and
      disability due to skeletal toxicities resulting from disease, its treatment and
      predisposing familial factors that contribute to the development of bone mineral
      density (BMD) deficits and osteonecrosis. Some technical limitations of imaging
      methods designed to assess BMD in skeletally mature adult patients are amplified
      when used to assess bone density in growing children and adolescents. Identifying
      changes in bone marrow that are associated with disease or treatment, and
      differentiating these that may heal in comparison to those likely to progress,
      have not been studied extensively in children. Until recently, little emphasis
      has been placed on the definition, characterization and prospective monitoring of
      these two major skeletal toxicities in pediatric patients, despite the growing
      attention being paid to the prevalence and severity of osteoporosis in adults.
      Further, the disease definitions established for adults are unlikely to apply to
      growing children. This presentation will discuss many of the issues related to
      defining, identifying, and classifying deficits in BMD and osteonecrosis, and
      will likely raise more issues than it answers.

PMID- 18064654
TI  - Nutritional status of children during treatment for acute lymphoblastic leukemia
      in the Central American Pediatric Hematology Oncology Association (AHOPCA):
      preliminary data from Guatemala.
AB  - Preliminary data reveal some degree of nutritional depletion in up to 54% of
      newly diagnosed children with acute lymphoblastic leukemia in Guatemala. Deaths
      due to abandonment of therapy and treatment failure were more common in under
      nourished than in well-nourished children when nutritional status was determined
      by arm anthropometry (mid upper arm circumference and triceps skin fold
      thickness). Given that these measures are less subject to variation between
      racial/ethnic groups than is the case with height and weight, it is recommended
      that arm anthropometry become part of the standard of care for children with
      cancer in developing countries.

PMID- 18064650
TI  - Epac/Rap and PKA are novel mechanisms of ANP-induced Rac-mediated pulmonary
      endothelial barrier protection.
AB  - Acute lung injury, sepsis, lung inflammation, and ventilator-induced lung injury
      are life-threatening conditions associated with lung vascular barrier
      dysfunction, which may lead to pulmonary edema. Increased levels of atrial
      natriuretic peptide (ANP) in lung circulation reported in these pathologies
      suggest its potential role in the modulation of lung injury. Besides well
      recognized physiological effects on vascular tone, plasma volume, and renal
      function, ANP may exhibit protective effects in models of lung vascular
      endothelial cell (EC) barrier dysfunction. However, the molecular mechanisms of
      ANP protective effects are not well understood. The recently described cAMP
      dependent guanine nucleotide exchange factor (GEF) Epac activates small GTPase
      Rap1, which results in activation of small GTPase Rac-specific GEFs Tiam1 and
      Vav2 and Rac-mediated EC barrier protective responses. Our results show that ANP
      stimulated protein kinase A and the Epac/Rap1/Tiam/Vav/Rac cascade dramatically
      attenuated thrombin-induced pulmonary EC permeability and the disruption of EC
      monolayer integrity. Using pharmacological and molecular activation and
      inhibition of cAMP-and cGMP-dependent protein kinases (PKA and PKG), Epac, Rap1,
      Tiam1, Vav2, and Rac we linked ANP-mediated protective effects to the activation
      of Epac/Rap and PKA signaling cascades, which dramatically inhibited the Rho
      pathway of thrombin-induced EC hyper-permeability. These results suggest a novel
      mechanism of ANP protective effects against agonist-induced pulmonary EC barrier
      dysfunction via inhibition of Rho signaling by Epac/Rap1-Rac and PKA signaling
      cascades.

PMID- 18064655
TI  - The Canadian Childhood Cancer Surveillance and Control Program (CCCSCP): a status
      report.

PMID- 18064656
TI  - Nutrition and cancer in children.

PMID- 18064657
TI  - Assessing mineral metabolism in children using stable isotopes.
AB  - Mineral metabolism may be altered in children with acute or chronic illnesses.
      The effects may be short term, such as hypomagnesemia associated with
      chemotherapy, or long-term, such as loss of bone mineral mass after steroid use.
      Understanding the causes, consequences, and potential therapies for mineral
      disorders is enhanced by understanding the absorption, body utilization, and
      turnover of these minerals. These assessments can now be done safely and readily
      using non-radioactive, stable isotopes which are available for calcium, zinc,
      magnesium, and iron. The methods for measurement of mineral absorption and
      kinetics (turnover) are well established, especially for calcium, and have been
      tested in every age group. Few studies, however, have been performed in children
      with acute or chronic illnesses such as cancer. Isotope dosing and infusion
      protocols are minimally invasive and protocols require small blood or urine
      volumes. Mineral absorption can be assessed without collecting fecal samples.
      Kinetics are assessed with blood and urine collections, usually over 5-10 days.
      Increased use of these techniques may be important in medical and nutritional
      assessment as well as in the management of pediatric oncology patients.

PMID- 18064658
TI  - Are survivors of acute lymphoblastic leukemia (ALL) at increased risk of
      cardiovascular disease?
AB  - Through a variety of different mechanisms, it appears that survivors of childhood
      acute lymphoblastic leukemia have an increased prevalence of several
      cardiovascular risk factors and thus are at increased risk for developing
      cardiovascular disease. The aim of this paper is to describe the current
      understanding of particular risk factors, including obesity, physical inactivity,
      dyslipidemia, insulin resistance, and metabolic syndrome, that may contribute to
      cardiovascular disease in survivors of childhood ALL. The potential roles of
      different cancer therapies in the development of these risk factors are
      discussed. In addition, two other late effects that may affect cardiovascular
      health are discussed: late-onset anthracycline-induced left ventricular
      dysfunction and methotrexate-mediated elevations of homocysteine during therapy
      with the potential for endothelial dysfunction. Lastly, areas needing further
      investigation to elucidate these risks are highlighted.

PMID- 18064660
TI  - Osteoporosis in children with cancer.
AB  - As increasing numbers of childhood cancer patients are surviving, the long-term
      complications of the disease and its treatment have become ever more increasingly
      important. Reduced bone mineral density and increased fracture risk have been
      reported during and after treatment of children with cancer. The causes of
      osteoporosis are multifactorial. Among others, the disease itself, chemotherapy,
      irradiation and genetic susceptibility play a role. Bone mineral density in later
      life depends largely on the peak bone mass achieved in adolescence or young
      adulthood. Therefore, optimizing peak bone mass is of clinical importance.
      Preventive and therapeutic strategies, such as calcium and vitamin D
      supplementation, physical activity and bisphosphonates, are considered.

PMID- 18064661
TI  - Prenatal supplementation with multivitamins and the incidence of pediatric
      cancers: clinical and methodological considerations.
AB  - Cancer is the second leading cause of death in children. Research has been
      undertaken to identify risk factors associated with pediatric cancers.
      Nevertheless one single cause has not been isolated. Recent studies have
      suggested that prenatal multivitamin consumption may be associated with the
      prevention of pediatric cancers. It has been shown previously that prenatal
      multivitamin ingestion is associated with a decrease in congenital anomalies. The
      following review summarizes the available knowledge associating prenatal
      multivitamin consumption with the prevention of pediatric cancers.

PMID- 18064662
TI  - Complementary and alternative (CAM) dietary therapies for cancer.
AB  - Complementary and alternative (CAM) therapies include a wide spectrum of dietary
      practices, some of which are claimed to cure cancer. Observational studies have
      shown consistently that predominantly plant-based diets reduce the risk for some
      adult type cancers such as breast cancer and prostate cancer. These studies form
      the basis of the American Cancer Society (ACS) nutritional guidelines. Many CAM
      diets prescribe a similar low fat, high fiber, high fruit and vegetable type
      diet, but also add detoxification and many different supplements to the basic
      diet which is then claimed to cure cancer. The potential advantages and
      disadvantages of CAM diets are discussed. Many aspects can be potentially
      harmful, particularly to the child with cancer. Advantages include involvement of
      the child and family in decision-making and care. There is no evidence to support
      the claims that CAM dietary therapies cure cancer.

PMID- 18064663
TI  - Nutritional status at diagnosis in children and adolescents with cancer in the
      Asociacion de Hemato-Oncologia Pediatrica de Centro America (AHOPCA) countries:
      preliminary results from Guatemala.
AB  - More than 50% of children with cancer in Guatemala have some degree of
      malnutrition at diagnosis. In particular, the proportions of patients with non
      lymphoblastic leukemias and myelodysplasia (MDS) with moderate and severe
      malnutrition were 73% and 9% respectively; higher than that in the population
      with acute lymphoblastic leukemia (ALL), P = 0.0493. There was no relationship of
      nutritional status to gender. Children with ALL and other leukemias + MDS who had
      severe malnutrition were significantly younger than such malnourished children
      with solid tumors (P = 0.0003). The relationship of malnutrition to race was
      mixed, perhaps reflecting the frequent difficulty of accurately categorizing
      race.

PMID- 18064665
TI  - Exercise running and tetracycline as means to enhance skeletal muscle stem cell
      performance after external fixation.
AB  - Prolonged limb immobilization, which is often the outcome of injury and illness,
      results in the atrophy of skeletal muscles. The basis of muscle atrophy needs to
      be better understood in order to allow development of effective countermeasures.
      The present study focused on determining whether skeletal muscle stem cells,
      satellite cells, are directly affected by long-term immobilization as well as on
      investigating the potential of pharmacological and physiological avenues to
      counterbalance atrophy-induced muscle deterioration. We used external fixation
      (EF), as a clinically relevant model, to gain insights into the relationships
      between muscle degenerative and regenerative conditions to the myogenic
      properties and abundance of bona fide satellite cells. Rats were treated with
      tetracycline (Tet) through the EF period, or exercise trained on a treadmill for
      2 weeks after the cessation of the atrophic stimulus. EF induced muscle mass
      loss; declined expression of the muscle specific regulatory factors (MRFs) Myf5,
      MyoD, myogenin, and also of satellite cell numbers and myogenic differentiation
      aptitude. Tet enhanced the expression of MRFs, but did not prevent the decline of
      the satellite cell pool. After exercise running, however, muscle mass, satellite
      cell numbers (enumerated through the entire length of myofibers), and myogenic
      differentiation aptitude (determined by the lineal identity of clonal cultures of
      satellite cells) were re-gained to levels prior to EF. Together, our results
      point to Tet and exercise running as promising and relevant approaches for
      enhancing muscle recovery after atrophy.

PMID- 18064666
TI  - Pressure loading and ethanol exposure differentially modulate rat hepatic
      stellate cell activation.
AB  - Ethanol may cause an increase in sinusoidal pressure accompanied by portal
      hypertension. Hepatic stellate cells (HSCs) located in hepatic sinusoids may
      therefore be frequently exposed to dual stimulations of mechanical pressure and
      ethanol exposure in alcoholic liver injury. In this study, the effects of
      pressure loading and ethanol exposure on activation of rat cultured HSCs were
      investigated using an in vitro pressure-inducing apparatus. HSCs were cultured in
      media containing ethanol (0-100 mM) under different pressures (1-40 mmHg).
      Morphological changes and migration index were determined. We also determined the
      expression levels of alpha-smooth muscle actin (alpha-SMA) and mitogen-activated
      protein kinases (MAPKs) by Western blot analysis and the level of collagen IV and
      transforming growth factor beta1 (TGF-beta1) by ELISA. Pressure loading alone
      induced up-regulation of alpha-SMA via the extracellular signal-regulated kinases
      1 and 2 (ERK1/2) and c-jun N-terminal kinase (JNK) signaling pathways, prolonged
      extension of marginal length, and increased production of collagen IV. In
      contrast, ethanol exposure alone increased only extension of marginal length and
      cell migration. Dual stimulations of pressure loading and ethanol exposure
      enhanced the production of TGF-beta1 and migration index. The TGF-beta1-dependent
      p38 MAPK pathway may operate for production of extracellular matrix (ECM) or
      enhanced migration in the case of dual stimulations. In conclusion, static
      pressure loading is an important factor directly accelerating the activation of
      HSCs. Although increased sinusoidal pressure and ethanol exposure might
      differentially modulate HSC activation, both stimuli are involved in an additive
      manner in some situations.

PMID- 18064668
TI  - Definition of normality of pressure-flow parameters based on observations in
      asymptomatic men.
AB  - AIMS: Clinical nomograms for differentiating obstructed from unobstructed voiding
      and poor detrusor contractility from normal contractility have traditionally been
      drawn on the basis of symptomatic response to outflow tract surgery or on
      urodynamic changes in men with LUTS before and after surgery. The aim of this
      study was to examine pressure-flow parameters in asymptomatic male volunteers
      before age-related changes in the lower urinary tract had taken place and to
      assess detrusor contractility and outflow conditions during physiological bladder
      filling against clinically used pressure-flow nomograms. METHODS: Thirty-seven
      healthy male subjects between the ages of 18 and 40 years volunteered to undergo
      AUM. A total of 66 fill-void cycles in 25 individuals were evaluable. RESULTS:
      Mean p(det.Qmax) for the group was 53 +/- 3 cmH(2)O with a mean Q(max) of 24 +/-
      2 ml sec(-1). URA of 21 cmH(2)O defined the upper border of normality for the
      outflow condition. Schafer's OCO showed the most consistent relationship between
      estimated urethral pressure at minimal flow and true measured urethral closure
      pressure. From a clinical perspective, the linear nomograms (ICS and Schafer) are
      more easily accessible with the ICS BOOI and obstruction index being the simplest
      to calculate manually. Minimal differences found between these urodynamic
      nomograms confirm the clinical value of recommending a single method to
      facilitate future comparisons between studies. CONCLUSIONS: An upper limit of
      normality for the male outflow condition can be defined by an URA of 21 cmH(2)O,
      AGN of 40 cmH(2)O or OCO of 1. Results above these reference values should be
      considered abnormal in this age group and where identified in a different age
      group should be explained by physiological or pathophysiological events.

PMID- 18064667
TI  - Osteoclast stimulatory transmembrane protein (OC-STAMP), a novel protein induced
      by RANKL that promotes osteoclast differentiation.
AB  - Microarray and real-time RT-PCR were used to examine expression changes in
      primary bone marrow cells and RAW 264.7 cells in response to RANKL. In silico
      sequence analysis was performed on a novel gene which we designate OC-STAMP.
      Specific siRNA and antibodies were used to inhibit OC-STAMP RNA and protein,
      respectively, and tartrate-resistant acid phosphatase (TRAP)+ multinucleated
      osteoclasts were counted. Antibodies were used to probe bone tissues and western
      blots of RAW cell extracts +/- RANKL. cDNA overexpression constructs were
      transfected into RAW cells and the effect on RANKL-induced differentiation was
      studied. OC-STAMP was very strongly up-regulated during osteoclast
      differentiation. Northern blots and sequence analysis revealed two transcripts of
      2 and 3.7 kb differing only in 3'UTR length, consistent with predictions from
      genome sequence. The mRNA encodes a 498 amino acid, multipass transmembrane
      protein that is highly conserved in mammals. It has little overall homology to
      other proteins. The carboxy-terminal 193 amino acids, however, are significantly
      similar to the DC-STAMP family consensus sequence. DC-STAMP is a transmembrane
      protein required for osteoclast precursor fusion. Knockdown of OC-STAMP mRNA by
      siRNA and protein inhibition by antibodies significantly suppressed the formation
      of TRAP+, multinucleated cells in differentiating osteoclast cultures, with many
      TRAP+ mononuclear cells present. Conversely, overexpression of OC-STAMP increased
      osteoclastic differentiation of RAW 264.7 cells. We conclude that OC-STAMP is a
      previously unknown, RANKL-induced, multipass transmembrane protein that promotes
      the formation of multinucleated osteoclasts.

PMID- 18064669
TI  - Magnetic colloids as drug vehicles.
AB  - This review article is a description of the present status of magnetic drug
      delivery systems (DDS). These are colloidal dispersions of composite
      nanoparticles consisting of a (polymeric or inorganic) biocompatible matrix and
      magnetic units, and designed to load and release therapeutic drugs. The matrix,
      together perhaps with adsorbed polymers or polyelectrolytes, provides the DDS
      with additional colloidal stability and eventually control of the immune
      response, and the magnetic inclusions have the goal of providing magnetic
      guidance. The techniques used in the production of the particles are described.
      The large surface/volume ratio of the particles brings about a superlative
      importance of the interface aspects, which are depicted in some detail. Attention
      is also paid to the possibilities that magnetic DDS offer to be guided by
      magnetic fields, and to their fate upon entering in contact with the blood
      proteins and the tumor cells. A description of in vitro and in vivo
      biodistribution experiments helps in this description. The number of animal
      experiments performed using magnetic DDS is rather large, but results in humans
      are far from being sufficient in number, something easily understood. The hopes
      for improvement and the challenges that must be overcome are described in the
      closing section.

PMID- 18064670
TI  - Paternally and maternally transmitted GAL4 transcripts contribute to UAS
      transgene expression in early Drosophila embryos.
AB  - The GAL4/UAS binary system with its recent modifications provides a powerful tool
      to study gene function in Drosophila enabling control over the timing, tissue
      specificity, and magnitude of gene expression. GAL4 expression during early
      embryonic stages has been well determined for certain driver lines, but for some
      of the commonly used in Drosophila research it is unknown, or partially
      determined. By monitoring the developmental kinetics of GAL4 expression and
      transgene transcription, we show that particular GAL4 drivers transiently direct
      ectopic expression of UAS-linked transgenes at early stages of embryogenesis in a
      GAL4- dependent manner via a mechanism that involves parental transmission of
      Gal4 transcripts.

PMID- 18064671
TI  - Transgenic mouse lines expressing Cre recombinase specifically in posterior
      notochord and notochord.
AB  - During development, the organizer provides instructive signals to surrounding
      cells as well as contributing cells to axial structures. To dissect organizer
      function at different developmental stages, conditional approaches such as the
      Cre/loxP system for conditional mutagenesis are particularly useful. Here we
      describe two new Cre transgenic mouse lines, Foxa2 NFP-Cre and Nodal PNC-Cre,
      with activity in two organizer domains, the posterior notochord (PNC) and
      notochord. These lines were made using defined regulatory elements from the Foxa2
      and Nodal genes that direct Cre expression in overlapping domains of the PNC and
      notochord. Our detailed analysis of the timing and location of Foxa2 NFP-Cre and
      Nodal PNC-Cre activity indicates that these lines are appropriate for conditional
      mutagenesis of genes expressed from early somite stages onward.

PMID- 18064673
TI  - Conditional tamoxifen Cre induced mutagenesis in the embryonic kidney in organ
      culture.
AB  - Developmental control genes are often sequentially and repeatedly functional
      during embryogenesis, and for this reason conditional mutagenesis tools are often
      required to study their roles in detail. Cre recombinase fused to the modified
      estrogen hormone-binding domain (ER(Tm)) generates a Cre in which the
      recombination activity of the LoxP-containing gene can be regulated by the
      nonsteroidal estrogen analogue 4-hydroxytamoxifen (4OH-TM). ER(Tm) may provide a
      useful way of achieving conditional mutagenesis in conjunction with the classic
      organ culture methods of experimental embryology. We used embryonic kidneys
      separated from the Cre-ER(Tm); R26R embryos to assay whether efficient 4OH-TM
      inducible genomic recombination can be achieved in organ culture and in
      experimentally induced kidney mesenchymes. Our results indicate that the
      inducible ER(Tm) Cre/loxP system indeed provides an effective way of
      conditionally mutagenizing genes in kidney organ culture and tissue conjugates.

PMID- 18064672
TI  - Genetic analysis of attractin homologs.
AB  - Attractin (ATRN) and Attractin-like 1 (ATRNL1) are highly similar type I
      transmembrane proteins. Atrn null mutant mice have a pleiotropic phenotype
      including dark fur, juvenile-onset spongiform neurodegeneration, hypomyelination,
      tremor, and reduced body weight and adiposity, implicating ATRN in numerous
      biological processes. Bioinformatic analysis indicated that Atrn and Atrnl1 arose
      from a common ancestral gene early in vertebrate evolution. To investigate the
      genetics of the ATRN system and explore potential redundancy between Atrn and
      Atrnl1, we generated and characterized Atrnl1 loss- and gain-of-function
      mutations in mice. Atrnl1 mutant mice were grossly normal with no alterations of
      pigmentation, central nervous system pathology or body weight. Atrn null mutant
      mice carrying a beta-actin promoter-driven Atrnl1 transgene had normal, agouti
      banded hairs and significantly delayed onset of spongiform neurodegeneration,
      indicating that over-expression of ATRNL1 compensates for loss of ATRN. Thus, the
      two genes are redundant from the perspective of gain-of-function but not loss-of
      function mutations.

PMID- 18064674
TI  - Generation of mice harboring a Sox4 conditional null allele.
AB  - Sox4 belongs to the family of Sry-related HMG box transcription factors, which
      specify cell fate and differentiation in many lineages. Sox4 is widely expressed
      in the embryo and controls such processes as neuronal tissue, lymphocyte, heart,
      and bone development. Sox4-null mice die at embryonic day 14 from heart
      malformation. This early lethality has therefore limited studies on Sox4
      functions. We show here that we have generated mice harboring a Sox4 conditional
      null allele (Sox4fl+) by flanking the entire coding region with loxP sites.
      Sox4fl+/fl+ mice are indistinguishable from wildtype mice and produce the
      wildtype Sox4 protein at a normal level. Sox4fl+ is efficiently converted into a
      null allele (Sox4fl-) by Cre recombinase in somatic and germ-line cells, and
      Sox4fl-/fl- embryos die from the same heart defects as Sox4-/- mice. This Sox4
      conditional null allele will thus be a valuable tool to further uncovering Sox4
      functions in various processes in vivo.

PMID- 18064675
TI  - Generation of mice with a conditional allele of the p120 Ras GTPase-activating
      protein.
AB  - p120 Ras GTPase-activating protein (RasGAP) encoded by the rasa1 gene in mice is
      a prototypical member of the RasGAP family of proteins involved in negative
      regulation of the p21 Ras proto-oncogene. RasGAP has been implicated in signal
      transduction through a number of cell surface receptors. In humans, inactivating
      mutations in the coding region of the RASA1 gene cause capillary malformation
      arteriovenous malformation. In mice, generalized disruption of the rasa1 gene
      results in early embryonic lethality associated with defective vasculogenesis and
      increased apoptosis of neuronal cells. The early lethality in this mouse model
      precludes its use to further study the importance of RasGAP as a regulator of
      cell function. Therefore, to circumvent this problem, we have generated a
      conditional rasa1 knockout mouse. In this mouse, an exon that encodes a part of
      the RasGAP protein essential for catalytic activity has been flanked by loxP
      recognition sites. With the use of different constitutive and inducible Cre
      transgenic mouse lines, we show that deletion of this exon from the rasa1 locus
      results in effective loss of expression of catalytically-active RasGAP from a
      variety of adult tissues. The conditional rasa1 mouse will be useful for the
      analysis of the role of RasGAP in mature cell types.

PMID- 18064676
TI  - Cre activity causes widespread apoptosis and lethal anemia during embryonic
      development.
AB  - Cre-mediated excision of targeted loxP sites is widely used to delete or to
      activate gene expression in temporal or tissue-specific fashions. We examine
      three previously described cre alleles and find that Cre activity alone causes
      dramatic developmental defects, such as loss of hematopoietic activity and
      dramatically upregulated apoptosis in many embryonic tissues in two of these
      lines. These results demonstrate that cre expression generates spurious
      phenotypes that can confound genetics analyses. We also find that most recently
      published studies fail to include cre-positive controls, and thus may have
      attributed roles to a targeted gene, which were in reality partly or wholly due
      to Cre toxicity. This information will be critical in both evaluating previously
      published work using cre alleles and in designing future experiments.

PMID- 18064677
TI  - Foxb1-driven Cre expression in somites and the neuroepithelium of diencephalon,
      brainstem, and spinal cord.
AB  - We have knocked-in Cre-IRES-EGFP in the Foxb1 locus by homologous recombination
      in embryonic stem cells. We removed the PGK-neo cassette (which was flanked by
      FRT sequences) by crossing with the FLPeR deleter mouse. The Foxb1(Cre) line
      showed Cre recombinase activity as well as EGFP fluorescence reproducing Foxb1
      expression accurately. By crossing Foxb1(Cre) mice with the ROSA26R and Z/AP
      mouse reporter lines we have been able to trace the lineage of Foxb1-expressing
      cells. Early transient expression of Foxb1 in the paraxial mesoderm translates
      into labeling of the somites. In the central nervous system (CNS), the Foxb1
      lineage includes the thalamus and mammillary body (hypothalamus), brainstem, and
      the ventral spinal cord and floor plate.

PMID- 18064678
TI  - Establishment of conditional knockout alleles for the gene encoding the regulator
      of telomere length (RTEL).
AB  - Regulator of telomere length (RTEL) is a DNA helicase-like protein that has
      recently been demonstrated to be required for the maintenance of telomere length
      and genomic stability. Rtel null mice are embryonic lethal with the defects in
      the nervous system, the heart, the vasculature, and extra-embryonic tissues. Rtel
      could also be important for the postnatal development as its expression is
      strongly induced in the proliferating adult cells. To further characterize the
      role of RTEL in adult tissue function and homeostasis, we have generated the
      floxed (loxP-flanked) alleles allowing to inactivate RTEL through Cre-mediated
      recombination in a cell- or tissue-specific manner and also to circumvent the
      embryonic lethality of the Rtel null allele. Mice heterozygous or homozygous for
      these alleles are viable and fertile. Crossing the floxed Rtel allele with a
      ubiquitous Cre transgenic line resulted in embryonic defects identical to those
      previously described for the Rtel null embryos. These conditional alleles will
      therefore be the important genetic tools for dissecting the spatial and temporal
      roles of RTEL in the regulation of telomere length and genomic stability during
      postnatal development and tumorigenesis.

PMID- 18064680
TI  - Calorimetric relaxation and the glass-liquid temperature range of acetaminophen
      nifedipine alloys.
AB  - Glassy states of nine acetaminophen-nifedipine compositions have been made by
      slowly supercooling their melts, and calorimetric T(g) and the nonexponential,
      nonlinear relaxation parameters beta and x that are used in modeling the mobility
      of a pharmaceutical determined. The T(g)-endotherm's shape varies with the
      alloy's composition, T(g) increases approximately linearly with the mol% of
      nifedipine, beta and x increase, and the activation enthalpy Deltah* decreases.
      At T(g), the relaxation time tau(cal) of acetaminophen, nifedipine, and their
      alloys differs from 100 s to different extents. The distribution of relaxation
      times is lesser than that for polymers and other glasses. For a given
      composition, Deltah*, beta, x, and tau(cal) anomalously depend upon the heating
      rate, indicating that variation of beta with temperature would not yield better
      fits for modeling their stability. It is suggested that a pharmaceutical's
      relaxation is generally influenced by changes in intermolecular hydrogen bonds,
      chemical short-range order, vibrational frequency, isomerization, and impurity
      electrolyte dissociation, all of which contribute to the energy change with a
      distinctive kinetics.

PMID- 18064681
TI  - Nano-sized assemblies of a PEG-docetaxel conjugate as a formulation strategy for
      docetaxel.
AB  - An amphiphilic polymer-drug conjugate was prepared by attachment of low molecular
      weight methoxy poly(ethylene glycol) (PEG) (i.e., 2 kDa) to docetaxel (DTX)
      through an ester linkage. The PEG-DTX conjugate having a critical micelle
      concentration of 0.88 mg/mL was used to form nano-sized micelles, with mean
      diameters of less than 100 nm, for solubilization of free DTX. The maximum
      concentrations of free and conjugated DTX achieved in this formulation were 28
      and 12 mg/mL (DTX equivalent), respectively; which corresponds to a drug to
      polymer ratio of 4:3 (w/w). The physico-chemical properties of the PEG-DTX
      conjugate and DTX formulation were evaluated including stability, rate of
      hydrolysis, hemolytic activity, and drug release profile. The anti-cancer
      activity of the drug in the PEG-DTX micelle formulation was demonstrated to be
      retained in three human cancer cell lines. Intravenous administration of DTX in
      the PEG-DTX micelles revealed relatively rapid dissociation of the free drug from
      the formulation; however, a 1.8-fold higher DTX equivalent area under the plasma
      concentration-time curve (AUC) was obtained, in comparison to DTX administered as
      Taxotere. The maximum tolerated dose of this DTX formulation was also 2.5-fold
      higher than that for Taxotere(R) in healthy mice.

PMID- 18064682
TI  - Use of in vitro human skin membranes to model and predict the effect of changing
      blood flow on the flux and retention of topically applied solutes.
AB  - The effect of dermal clearance on epidermal concentrations of topically applied
      drugs is poorly understood but fundamental to absorption kinetics and efficacy.
      Previously generated data quantifying changes in flux and epidermal retention of
      a series of alcohols and steroids was used to relate solute physicochemical
      properties to changes in flux under conditions of infinite vasoconstriction (full
      thickness skin) and infinite vasodilatation (epidermal membranes) using stepwise
      regression. Flux through full-thickness skin decreased with increasing
      lipophilicity, up to 45-fold for alcohols and 4-fold for steroids. This change in
      flux was not uniformly predictable for the solutes, with alcohols showing a
      strong dependency on molecular weight (MW), indicative of stratum corneum
      diffusion limited penetration. Epidermal retention of lipophilic solutes was
      found to increase up to sixfold in full-thickness skin, with changes predictable
      from a combination of log P and MW (correlation 0.898, p < 0.001). This study
      shows that drug epidermal retention and penetration is significantly affected by
      dermal clearance, however aspects of these effects may be able be predicted from
      solute physicochemical properties, though extrapolation of the results of this
      study to other solute-membrane combinations remains to be proven. These findings
      have significant implications in understanding the effects of erythema and
      vasoconstriction on topical drug efficacy.

PMID- 18064683
TI  - Solid renal masses in adults: image-guided fine-needle aspiration cytology and
      imaging techniques--"two heads better than one?".
AB  - We have compared the diagnostic accuracy of image-guided 25G-FNA (fine-needle
      aspiration) and imaging modalities in a group of 31 patients with solid space
      occupying renal lesions. All patients had undergone total nephrectomy and
      histologic sections were available for review. By FNA there were 24 malignant
      diagnoses, I benign diagnosis, and 6 cases with yield inadequate for diagnosis.
      The FNA accuracy for malignancy was 100% with no false positive cases; cancer
      typing by FNA matched the final histologic diagnoses in 91.6% of cases.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value were 80%, 14%, 80%, and 14%, respectively. Radiologically there were 26
      diagnoses of malignancy, I of benignity, and 4 indeterminate lesions (IL).
      Accuracy for malignancy was 100%, with one false positive case; cancer typing
      matched the final histologic diagnoses in 84%. Sensitivity of imaging modalities
      was 86%, specificity 17%, positive predictive value 83%, and negative predictive
      value 20%. Four IL corresponded to renal cell carcinoma in the final histologic
      report: two IL had a previous diagnosis of malignancy by FNA, and the yield of
      two was inadequate for cytologic diagnosis. Both techniques have 100% accuracy
      for the diagnosis of malignancy. The sensitivity, specificity, positive
      predictive value, and negative predictive value of imaging techniques are
      slightly higher than those obtained by FNA. Imaging techniques and FNA of solid
      renal masses complement each other in IL and in nondiagnostic FNAs.

PMID- 18064684
TI  - A comparision of aspiration cytology and core needle biopsy according to tumor
      size of suspicious breast lesions.
AB  - The purpose of the study was to compare the accuracy of FNAC, CNB, and combined
      biopsy according to tumor size of suspicious breast lesions. FNAC and CNB were
      performed in 264 patients with suspicious breast lesions from August, 1997 to
      August, 2002. The procedures were guided by ultrasound and performed in the same
      session by the same operator. The lesions were divided in four groups according
      to the tumor size in the histopathology report: lesions smaller than 1 cm,
      between 1 and 2 cm, between 2 and 5 cm, and lesions greater than 5 cm. The final
      surgical histopatology results identified 222 (84%) malignant cases and benign
      lesions summed 42 (16%). For lesions smaller than 1 cm, FNAC, CNB, and combined
      biopsy were equivalent for all parameters. For lesions between 1 and 2 cm, FNAC
      and CNB were equivalent. Combined biopsy showed higher absolute sensitivity (P =
      0.007) and lower inadequate rate (P = 0.03) when compared to FNAC. However, when
      combined biopsy and CNB were compared, no difference were found. For lesions
      between 2 and 5 cm, CNB showed higher absolute sensitivity (P < 0.001) and lower
      inadequate rate (P < 0.007) when compared to FNAC. Combined biopsy showed higher
      sensitivity compared to FNAC and CNB alone (P < 0.05) in this group. For lesions
      greater than 5 cm, FNAC and CNB were equivalent for all parameters. Combined
      biopsy only showed higher absolute sensitivity (P = 0.04) when compared with FNAC
      alone. The combination of FNAC and CNB can improve the diagnosis of suspicious
      breast lesions higher than 1 cm. However, for lesions smaller than 1 cm, our
      results showed no difference between FNAC, CNB, and combined biopsy, for these
      lesions any modality has technical limitations.

PMID- 18064685
TI  - Endoscopic ultrasound-guided fine needle aspiration is useful for nodal staging
      in patients with pleural mesothelioma.
AB  - Patients with malignant pleural mesothelioma and negative N2 stage lymph nodes
      may benefit from extrapleural pneumonectomy with adjuvant therapy. The objective
      of this study is to describe the use of EUS-FNA to determine N2 stage status in
      patients with mesothelioma and its impact in the management of such patients. Six
      patients (mean age, 62 yr; median age, 63 yr; range, 52-70 yr; 5 men; 1 woman)
      underwent EUS-FNA for staging of N2 lymph nodes from July 2000 to July 2006.
      Follow-up included operative notes, treatment summaries, and surgical pathology.
      Eight sites were aspirated: four subcarinal lymph nodes, three aorto-pulmonary
      window lymph nodes, and one paraesophageal mass. Two of 8 (25%) aspirates were
      positive for metastatic disease in two different patients. Two false negative EUS
      FNAs were observed and were attributed to sampling error not diagnostic error. No
      complications were observed. EUS-FNA is a safe N2 node staging technique in
      patients with mesothelioma. A positive N2 lymph node by EUS-FNA may be a
      contraindication to definitive surgery in patients with malignant mesothelioma.

PMID- 18064686
TI  - Cytopathology of a primary follicular dendritic cell sarcoma of the liver of the
      inflammatory pseudotumor-like type.
AB  - Follicular dendritic cell (FDC) sarcoma is an exceedingly uncommon tumor of lymph
      nodes and extranodal tissues. The inflammatory pseudotumor (IPT)-like variant of
      FDC sarcoma of intraabdominal location is considered a separate entity, with
      different clinical and pathological features than those of the classic FDC tumor.
      There have been only 12 cytological reports of FDC sarcomas in the literature.
      Two of them were metastases to the liver and, like our case, had features of IPT.
      Fine-needle aspiration biopsy (FNAB) and imprint and scrape cytology from the
      surgically excised tumor here reported revealed spindle tumor cells with moderate
      pleomorphism, nuclear grooves, prominent nucleoli, and cytoplasmic processes,
      admixed with inflammatory cells. To the best of our knowledge, this is the first
      cytology report of a primary hepatic FDC tumor. The cytological findings permit
      the recognition of this tumor. However, confirmation by inmunohistochemistry
      (IHQ) is mandatory for a definitive diagnosis.

PMID- 18064687
TI  - Nephrogenic adenoma identified on urine cytology using PAX-2 immunostaining.
AB  - Urine cytology is a sensitive and specific method in detecting urothelial
      carcinoma of the urinary bladder, particularly the high-grade ones. However, the
      cytologic features of nonneoplastic lesions of the lower urinary tract, including
      nephrogenic adenoma, are nonspecific and may cause false positive diagnosis.
      Recent evidence has demonstrated that nephrogenic adenoma is a true "nephrogenic"
      lesion derived from the exfoliated and implanted renal tubular cells in the
      urinary tract. This has promoted the use of immunostaining of renal transcription
      factor PAX2 in tissue biopsies to differentiate nephrogenic adenoma from the
      common malignant tumors of the lower urinary tract. We report here that PAX2
      immunostaining can also be used in urine cytology specimen to identify
      nephrogenic adenoma. Combination of PAX2 immunostaining and cytologic analysis
      may increase the accuracy in identifying this benign lesion in urine cytology
      specimen and therefore reduce unnecessary repeat cystoscopy and biopsy
      procedures. This may be a cost effective follow- up method for patients with an
      established diagnosis of nephrogenic adenoma.

PMID- 18064688
TI  - False-positive interpretations in respiratory cytopathology: exemplary cases and
      literature review.
AB  - Pulmonary cytology has progressed over the past decades because of advancement in
      imaging studies and increased confidence of pathologists in cytomorphologic
      diagnosis. It has an overall sensitivity and specificity ranging from
      approximately 60 to 96%. However, even with the most conscientious laboratories,
      false-positive diagnoses of malignancy do occur in respiratory specimens,
      potentially resulting in unnecessary treatment and morbidity. Selected
      respiratory cytopathology cases with false-positive diagnoses are presented here,
      along with a review of pertinent literature and a discussion of possible steps to
      minimize the problem being considered.

PMID- 18064689
TI  - Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6)
      immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and
      malignant mesothelioma in effusions.
AB  - To distinguish carcinoma, either adenocarcinoma (ADC) or squamous cell carcinoma
      (SCC), and malignant mesothelioma (MM) in effusion can be a diagnostic challenge
      based on morphology alone. This study evaluates the utility of WT-1, p63, MOC31,
      mesothelin, and cytokeratin (K903 and CK5/6) immunostains in effusions when ADC
      and SCC of the lung are in the differential diagnosis with MM. A cohort of 43
      effusions consisting of lung ADC (N = 10), SCC (N = 15), and MM (N = 18, mostly
      (16) pleural based), was subjected to immunostains using the above mentioned
      antibodies. WT-1 was positive in 100% MM, 0% ADC, and 0% SCC cases while p63 was
      positive in 0% MM, 30% ADC, and 80% SCC cases. Stain for MOC31 was positive in
      100% ADC, 67% SCC, and 35% MM cases. Similarly, mesothelin antibody stained 100%
      ADC, 60% SCC, and 47% MM cases. Antibodies for K903 and CK5/6 stained 100% SCC
      cases but fewer ADC cases (40 and 10%, respectively). In conclusion, in this
      cohort of mostly pleural malignant effusion, MM can be identified with positive
      staining for WT-1 and negative staining for p63. Conversely, negative staining
      with WT-1 and positive staining for p63 exclude MM. Used as part of an
      immunostain panel, cytokeratin markers (CK5/6 and K903) are useful in
      differentiating SCC from ADC when MM is already excluded, and MOC31 might have
      limited value in differentiating ADC from MM. A negative stain with MOC31 can
      exclude lung ADC. Mesothelin, on the other hand, is not useful in the
      differential diagnosis of ADC, SCC, and MM.

PMID- 18064690
TI  - Striking aquatic life structure found in a sputum smear.

PMID- 18064691
TI  - ThinPrep are superior to conventional smears in the cytological diagnosis of
      subfertile men by testicular fine-needle aspiration.
AB  - The aim of this study was the comparison of liquid-based cytology (ThinPrep, TS)
      to conventional smears (CS) in the investigation of subfertile men with
      testicular fine-needle aspiration (FNA). Between January and December 2004,
      testicular FNA biopsies were performed in 30 subfertile men. Both TS and CS were
      diagnosed according to Meng classification. Features specifically recorded in
      each smear included sample adequacy, tissue cells preservation, contamination
      with red blood cells, quality of smear background, ease of cell recognition, and
      the cytological diagnosis. There was agreement in the cytological diagnosis
      between TS and CS (P = 0.88) and sample adequacy (P = 0.73). TS was superior to
      CS regarding cell preservation, presence of red blood cells or tissue artifacts,
      quality of the smear background, and cell recognition (P < 0.0001). In testicular
      FNA cytology, TS appear to be superior to CS in respect to cell preservation,
      absence of red blood cells, background quality, and cell recognition. These
      advantages, however, are not translated in improved cytological diagnosis.

PMID- 18064692
TI  - Microfilariae in thyroid aspiration smear--an unexpected finding.
AB  - Lymphatic filariasis is a major health problem in tropical countries including
      India. Despite its high incidence it is difficult to find microfilariae in blood
      and fine-needle aspirates due to the nocturnal periodicity of species endemic in
      India. Lymphatic filariasis can manifest as asymptomatic microfilaremia,
      hydrocele, lymphangitis, and lymphadenitis. The presence of microfilariae in
      thyroid aspirates is a rare finding. A case of microfilariae in a thyroid
      aspirate is being reported to emphasize the significance of careful screening of
      smears in endemic areas.

PMID- 18064693
TI  - Scrape cytology of myositis ossificans: report of a case and analysis of the
      cytologic findings described previously.
AB  - Myositis ossificans is a reactive, ossifying process within soft tissues, which
      by its clinical and histological features is considered a pseudosarcomatous
      lesion. There are few reports that describe the cytologic findings in myositis
      ossificans, and each of these mentions different cellular composition. We
      describe the cytology of a case of myositis ossificans in a 14-year-old boy with
      clinical diagnosis of soft tissue sarcoma, and analyze the most common cytologic
      findings reported previously of this entity. We conclude that the different
      cellular composition reported, reflects the different histologic components of
      this lesion according to the area (zonation phenomenon), and that clinico
      radiologic correlation is essential for the cytological diagnosis.

PMID- 18064694
TI  - Granular cell tumor of the neurohypophysis: report of a case with intraoperative
      cytologic diagnosis.
AB  - Cytological techniques including touch and smear preparations are very useful
      diagnostic modality in the evaluation of central nervous system (CNS) lesions
      and, in many instances, may be effectively used as the sole modality of tissue
      preparation for intraoperative consultation. Cytologic preparations offer many
      advantages over frozen sections for CNS specimens. These include selective
      examination of multiple areas from small biopsy specimens, superior preservation
      and details of cellular morphology, fewer artifacts, faster results, and improved
      cost-effectiveness. We describe the cytologic diagnosis of a granular cell tumor
      (GCT) of the neurohypophysis in a 33-year-old male who presented with headache
      and blurred vision. CT scan revealed an enlarged sella with a 2.15 x 2.0 cm
      pituitary lesion. Transsphenoidal resection of the mass was performed and
      submitted for intraoperative consultation. Smears and touch preparations were
      made on a portion of the mass that showed uniform polygonal cells with round to
      ovoid nuclei and abundant eosinophilic granular cytoplasm. An intraoperative
      cytological diagnosis of "favor GCT" was rendered. The histologic sections of the
      remaining material confirmed the diagnosis. Although GCT of the neurohypophysis
      is very rare, a specific intraoperative cytological diagnosis is possible. We
      report the clinical, cytological, and pathological findings of a GCT affecting
      the neurohypophysis.

PMID- 18064695
TI  - Adenoid cystic variant of papillary thyroid carcinoma: a case report with fine
      needle aspiration cytology.

PMID- 18064696
TI  - Synchronous metastases to the liver and pancreas from a primary neuroendocrine
      carcinoma of the breast diagnosed by fine-needle aspiration.
AB  - Extrapulmonary neuroendocrine carcinoma is uncommon. Cases of primary
      neuroendocrine carcinoma of the breast have been reported, though rare. We report
      the case of a 53-year-old woman who underwent a mastectomy for breast carcinoma
      and presented three years later with synchronous masses in the head of the
      pancreas and liver. Fine-needle aspiration of both organs revealed a
      neuroendocrine carcinoma. The original breast tumor was reviewed and found to
      express neuroendocrine markers. A diagnosis of a primary neuroendocrine carcinoma
      of the breast was rendered.

PMID- 18064697
TI  - Emperipolesis in the cerebrospinal fluid from a patient with Rosai-Dorfman
      disease.

PMID- 18064698
TI  - Evaluation of the impact of surfactant digestion on the bioavailability of
      danazol after oral administration of lipidic self-emulsifying formulations to
      dogs.
AB  - Lipid-based formulations of danazol with varying quantities of included
      surfactant have been examined in vitro and in vivo. Formulations comprising fatty
      acid ester surfactants were readily hydrolysed during in vitro digestion,
      although Cremophor RH40 (CrRH) was less effectively hydrolysed than Cremophor EL
      (CrEL). Formulations comprising high quantities of digestible surfactant also
      appeared to less effectively prevent danazol precipitation during in vitro
      evaluation. These trends were replicated in vivo where danazol bioavailability in
      beagle dogs was higher after oral administration of self-emulsifying formulations
      employing 55% (w/w) CrRH when compared with CrEL. The oral bioavailability of
      danazol after administration of drug formulated in surfactant alone, however, was
      poor. Studies using predispersed and encapsulated formulations of CrRH
      subsequently suggested that the low bioavailability of the single surfactant
      formulations reflected poor dispersion. Mixtures of surfactants, improved
      dispersion and good oral bioavailability of danazol was evident after
      administration of formulations comprising CrRH and either Pluronic L121 or
      Gelucire 44-14, in spite of evidence of danazol precipitation during in vitro
      digestion of the Gelucire formulation. These data suggest that effective
      dispersion and resistance to precipitation during both dispersion and digestion
      are key design parameters for lipid-based formulations comprising high
      proportions of surfactant.

PMID- 18064699
TI  - Structural characterization of the medfly hsp83 gene and functional analysis of
      its proximal promoter region in vivo by germ-line transformation.
AB  - In order to define the regulatory elements responsible for the expression of the
      medfly hsp83 (Cchsp83) gene, we determined the sequence of a genomic region of
      the gene that included 3,536 bp upstream of the transcription initiation site,
      the first untranslated exon of 144 bp, a 275-bp intron, and 516 bp of the second
      coding exon. Structural analysis of the 5' flanking region revealed the presence
      of a typical TATA box, 28 bp upstream of the transcription start site, and seven
      putative heat shock elements (HSEs) further upstream. The 5' untranslated region
      of the Cchsp83 mRNA was found to contain extensive secondary structure in the
      first 126 nucleotides. We carried out deletion functional analysis of the
      proximal promoter region (-380/+139) in vivo by germ line transformation using
      the lacZ as a reporter gene. We found that sequences in the -380/-86 region are
      essential for the constitutive expression of the Cchsp83 gene. Under normal
      conditions, the -380/+139 region was able to drive significant levels of
      transgene expression in all developmental stages of the medfly as well as in the
      ovaries and testis. In most stages, the temporal expression pattern of the
      reporter gene was similar to the respective pattern of the endogenous Cchsp83
      gene. Although the -380/+139 promoter region contained two putative HSEs, it was
      found unable to confer any heat-induced expression in the reporter gene.

PMID- 18064700
TI  - Lateral and rotational mobility of some drug molecules in a poly(ethylene glycol)
      diacrylate hydrogel and the effect of drug-cyclodextrin complexation.
AB  - In relation to drug release properties the lateral and rotational mobility of two
      drugs and one drug mimic in photopolymerized poly(ethylene glycol) diacrylate
      (PEGDA) networks were investigated by nuclear magnetic resonance as a function of
      the network cross-link density and temperature. The network mesh size affects the
      lateral diffusivity for all drugs, even if the mesh size is an order of magnitude
      larger than the drug molecular size. The rotational diffusional motion is only
      appreciably affected when the drug size and network mesh size are of the same
      order of magnitude. By complexing the drug to cyclodextrin (CD) it is found that
      in some cases, depending on network mesh size and complex size, the complex is
      absorbed by the PEGDA gel, but that the diffusion of the drug in the gel is not
      necessarily slower than in the absence of the CD. This is explained by a
      theoretical model.

PMID- 18064701
TI  - Carbohydrate accumulation and utilization by oocytes of Rhodnius prolixus.
AB  - The processes of accumulation and mobilization of carbohydrate stores in eggs of
      Rhodnius prolixus were analyzed. During oogenesis, the total amounts of glycogen,
      glucose, and trehalose increased with an accumulation of proteins, especially
      when oocytes grew from 1.0 to 1.5 mm in length. At 2.0 mm length, when oocytes
      were ready for oviposition, nutrient reserves did not increase appreciably and
      trehalose content decreased. Mating did not affect the final content of
      carbohydrates or proteins in oocytes of mated and virgin females. A trehalase
      activity was detected in follicles containing vitellogenic oocytes, 1.0 and 1.5
      mm length, in both mated and virgin females. This activity was extremely low in
      chorionated, 2.0-mm oocytes. After oviposition, glycogen content decreased in
      fertilized eggs, but not in unfertilized ones, and some was present in newly
      hatched nymphs. Glucose content remained constant in unfertilized eggs, but
      increased in fertilized ones, while total protein amount was constant in both
      groups after egg laying.

PMID- 18064702
TI  - Prominent down-regulation of storage protein genes after bacterial challenge in
      eri-silkworm, Samia cynthia ricini.
AB  - We constructed two independent cDNA libraries from the fat body of Escherichia
      coli- or Candida albicans-challenged eri-silkworm Samia cynthia ricini larvae. We
      performed comparative expressed sequence tag (EST) analysis of the two cDNA
      libraries and found that two putative storage protein genes, ScSP1 and ScSP2,
      were markedly repressed by E. coli injection as compared with C. albicans
      injection. By quantitative real-time RT-PCR analysis, we showed that ScSP1 mRNA
      significantly reduced to 1/32-1/3 in the fat body of the female larvae, and ScSP2
      mRNA reduced to 1/7-1/3 and 1/22-1/5 in the females and males, respectively, 12
      36 h after E. coli injection as compared with PBS injection. In addition, SDS
      PAGE analysis revealed that the accumulation of both the ScSP proteins in the
      larval hemolymph apparently decreased up to 36 h after E. coli injection.
      However, the amounts of the two ScSP proteins returned to the same level as those
      in the larvae injected with PBS by 48 h after injection, showing that the
      reduction in ScSPs caused by the bacterial challenge was transient. Moreover,
      potential binding sites for the Drosophila Rel/NF-kappaB protein Dorsal were
      found in the 5' upstream regulatory regions of ScSP1 and ScSP2, suggesting the
      participation of the Rel/NF-kappaB proteins in controlling the bacterial
      suppression of the ScSP genes. These results suggested the hypothesis that S. c.
      ricini has a genetic program to shut down temporarily dispensable gene expression
      in order to induce an acute and efficient expression of immune-related genes.
      These findings may provide new insight into the innate immune system in
      lepidopteran insects.

PMID- 18064703
TI  - Yield optimization of regulated metabolic systems using deterministic branch-and
      reduce methods.
AB  - This paper addresses product yield optimization in microorganisms grown in
      continuous culture. Traditional optimization strategies of random mutagenesis and
      selection will eventually have limited efficacy, thus requiring more focused
      strategies. The best candidates for such strategies appear to be mathematical
      models that capture the essence of metabolic systems and permit optimization with
      computational methods. In the past, models used for this purpose have been
      stoichiometric, kinetic in the form of S-systems, or ad hoc. This work presents a
      deterministic approach based on generalized mass action (GMA) systems. These
      systems are interesting in that they allow direct merging of stoichiometric and S
      system models. Two illustrations are considered. In the first case, the
      fermentation pathway in Saccharomyces cerevisiae is optimized for ethanol
      production under steady-state conditions. The model of this pathway is relatively
      small, with five states and eight rate constants. The second example addresses
      the maximization of citric acid in the mold Aspergillus niger. For the
      optimization of this larger pathway system with 30 states and 60 reactions, a
      Mixed Integer Nonlinear Programming (MINLP) is proposed. It is shown that
      efficient MINLP algorithms, based on convexification, branch-and-reduce methods,
      and binary variable selection, are essential for solving these difficult
      optimization problems.

PMID- 18064704
TI  - Understanding medial temporal activation in memory tasks: evidence from fMRI of
      encoding and recognition in a case of transient global amnesia.
AB  - We used fMRI to examine the activation patterns of patient AE during encoding and
      recognition of visual scenes during an episode of transient global amnesia (TGA)
      and 3 months later. Controls (n = 5) showed bilateral (R > L) activation in
      parahippocampal and fusiform gyri during encoding and right-sided activation in
      the same regions associated with recognition of previously viewed scenes. AE
      showed a similar pattern at follow-up. During acute TGA, when performance was
      profoundly impaired, AE showed no medial temporal activation associated with
      encoding of new scenes or recognition of old scenes. In both contrasts, the
      percent signal change in relevant medial temporal regions was more than three
      standard deviations below the control sample mean. She did, however, show
      striking bilateral hippocampal activation for recognition attempts (old + new
      scenes > baseline) even though retrieval was unsuccessful (55% recognition
      accuracy). This finding was unique to AE on this occasion. This is the first
      study to document normalization of both encoding and recognition activation
      patterns in TGA. Furthermore, the strong hippocampal activation during
      unsuccessful retrieval highlights important issues in interpreting memory-related
      activations, particularly in dysfunctional systems.

PMID- 18064705
TI  - Ventral hippocampal involvement in temporal order, but not recognition, memory
      for spatial information.
AB  - The hippocampus is critical for spatial memory. Recently, subregional differences
      in the function of hippocampus have been described in a number of behavioral
      tasks. The present experiments assessed the effects of reversibly lesioning
      either the dorsal (dHip) or ventral hippocampus (vHip) on spontaneous tests of
      spatial recognition and temporal order memory. We report that although the dHip
      is necessary for spatial recognition memory (RM) (distinguishing a novel from a
      familiar spatial location), the vHip is involved in temporal order memory (the
      capacity to distinguish between two spatial locations visited at different points
      in time), but not RM. These findings and others are consistent with the
      hypothesis that temporal order memory is supported by an integrated circuit of
      limbic areas including the vHip and the medial prefrontal cortex.

PMID- 18064707
TI  - Expression of free fatty acid receptor GPR40 in the neurogenic niche of adult
      monkey hippocampus.
AB  - Polyunsaturated free fatty acids (PUFAs) are known to play critical roles for the
      development, maintenance, and function of the brain. Recently, we reported that G
      protein coupled receptor 40 (GPR40), one type of PUFA receptors, is expressed
      throughout the adult primate central nervous system including the hippocampus.
      This opens a possibility that PUFA might act as extracellular signaling molecules
      at the GPR40 receptor to regulate neuronal function. Here we studied protein
      expression of GPR40 in the neurogenic niche of the adult monkey hippocampus under
      normal and postischemic conditions. Confocal laser microscope analysis of
      immunostained sections revealed GPR40 immunoreactivity in neural progenitors,
      immature neurons, astrocytes and endothelial cells of the subgranular zone (SGZ)
      of the dentate gyrus (DG); a well-known neurogenic niche within the adult brain.
      Immunoblotting analysis showed that the GPR40 protein increased significantly in
      the second week after global cerebral ischemia as compared with the control. This
      was compatible with the postischemic increment of GPR40-positive cells in the SGZ
      as detected by immunofluorescence imaging. Taken together with our previous
      findings of the SGZ progenitor cell upregulation after ischemia, the present data
      suggest that PUFA such as docosahexaenoic acid may act via GPR40 to regulate
      adult hippocampal neurogenesis in primates.

PMID- 18064708
TI  - Sensory gating in the human hippocampal and rhinal regions: regional differences.
AB  - To further explore the roles of medial temporal structures in mediating sensory
      gating of incoming irrelevant or redundant auditory input, twenty-seven patients
      with intractable epilepsy with depth electrodes implanted in the medial temporal
      lobe for presurgery evaluation underwent evoked response recording to auditory
      paired-stimuli (S1-S2). Seventeen subjects were diagnosed with left medial
      temporal lobe epilepsy (MTLE) and 10 with right MTLE. Only data from the
      nonlesion side were included. Twenty-three records from rhinal and anterior
      hippocampal regions, and 21 from posterior hippocampal regions were included in
      the analysis. The rhinal region had two prominent components (a negativity
      peaking around 200 ms followed by a positivity peaking around 400 ms). Both the
      anterior and posterior hippocampal regions exhibited a dominant negative
      potential peaking around 400 ms. These components were all composed predominantly
      of slower frequencies. In contrast, a negativity in the posterior hippocampus at
      around 100 ms was composed of slow and fast frequencies. All components but the
      early rhinal negativity were attenuated by stimulus repetition. This is the first
      report documenting that different regions of the medial temporal area are
      differentially involved in the processing of auditory input, most likely
      reflecting separate steps of processing. The data support the need for further
      exploration of the contribution of these regions to sensory gating. This
      information helps to increase our understanding of this basic but important and
      complex function.

PMID- 18064706
TI  - Cadherin-8 and N-cadherin differentially regulate pre- and postsynaptic
      development of the hippocampal mossy fiber pathway.
AB  - Cells sort into regions and groups in part by their selective surface expression
      of particular classic cadherins during development. In the nervous system,
      cadherin-based sorting can define axon tracts, restrict axonal and dendritic
      arbors to particular regions or layers, and may encode certain aspects of synapse
      specificity. The underlying model has been that afferents and their targets hold
      in common the expression of a particular cadherin, thereby providing a
      recognition code of homophilic cadherin binding. However, most neurons express
      multiple cadherins, and it is not clear whether multiple cadherins all act
      similarly in shaping neural circuitry. Here we asked how two such cadherins,
      cadherin-8 and N-cadherin, influence the guidance and differentiation of
      hippocampal mossy fibers. Using organotypic hippocampal cultures, we find that
      cadherin-8 regulates mossy fiber fasciculation and targeting, but has little
      effect on CA3 dendrites. In contrast, N-cadherin regulates mossy fiber
      fasciculation, but has little impact on axonal growth and targeting. However, N
      cadherin is essential for CA3 dendrite arborization. Both cadherins are required
      for formation of proper numbers of presynaptic terminals. Mechanistically, such
      differential actions of these two cadherins could, in theory, reflect coupling to
      distinct intracellular binding partners. However, we find that both cadherins
      bind beta-catenin in dentate gyrus (DG). This suggests that cadherins may engage
      different intracellular signaling cascades downstream of beta-catenin, coopt
      different extracellular binding partners, or target distinct subcellular domains.
      Together our findings demonstrate that cadherin-8 and N-cadherin are critical for
      generating the mossy fiber pathway, but that each contributes differentially to
      afferent and target differentiation, thereby complementing one another in the
      assembly of a synaptic circuit.

PMID- 18064709
TI  - Effects of inflammatory response on in vivo transgene expression by plasmid DNA
      in mice.
AB  - To examine the effects of inflammatory response to plasmid DNA (pDNA) on
      transgene expression, serum tumor necrosis factor-alpha (TNF-alpha) was measured
      after intravenous injection of pDNA or calf thymus DNA (CT DNA) in the naked or
      complexed form with cationic liposomes (lipoplex). pDNA with many CpG motifs
      induced TNF-alpha production regardless of the forms. No significant TNF-alpha
      production was detected when CT DNA or methylated pDNA was injected. Clodronate
      liposomes and dexamethasone were used to deplete phagocytes or to inhibit
      inflammatory responses, respectively. Transient depletion of phagocytes, such as
      liver Kupffer cells and splenic macrophages, by clodronate liposomes slightly
      altered the tissue distribution of (32)P-pDNA lipoplex, but significantly reduced
      the TNF-alpha production and transgene expression. Dexamethasone significantly
      inhibited the initial transgene expression, but increased the duration of the
      expression slightly. Use of NF-kappaB activity-dependent plasmid vector suggested
      that the inhibition of NF-kappaB activation is involved in the reduced expression
      by these treatments. These findings indicate that tissue macrophages are closely
      involved in the CpG motif-dependent TNF-alpha production. It is also suggested
      that TNF-alpha activates NF-kappaB and increases transgene expression by pDNA
      having many NF-kappaB binding sites, but TNF-alpha also reduces transgene
      expression at later time periods, leading to short-term transgene expression.

PMID- 18064710
TI  - Population-based birth defects surveillance data from selected states, 2000-2004.

PMID- 18064713
TI  - Collection, use, and protection of population-based birth defects surveillance
      data in the united states.
AB  - Birth defects surveillance systems collect population-based birth defects data
      from multiple sources to track trends in prevalence, identify risk factors, refer
      affected families to services, and evaluate prevention efforts. Strong state and
      federal public health and legal mandates are in place to govern the collection
      and use of these data. Despite the prima facie appeal of "opt-in" and similar
      strategies to those who view data collection as a threat to privacy, the use of
      these strategies in lieu of population-based surveillance can severely limit the
      ability of public health agencies to accurately access the health status of a
      group within a defined geographical area. With the need for population-based data
      central to their mission, birth defects programs around the country take their
      data stewardship role seriously, recognizing both moral and legal obligations to
      protect the data by employing numerous safeguards. Birth defects surveillance
      systems are shaped by the needs of the community they are designed to serve, with
      the goal of preventing birth defects or alleviating the burdens associated with
      them.

PMID- 18064714
TI  - Comparison of fat quantification methods: a phantom study at 3.0T.
AB  - PURPOSE: To compare different imaging methods with single-voxel MR spectroscopy
      (MRS) for the quantification of fat content in phantoms at 3.0T. MATERIALS AND
      METHODS: Imaging and spectroscopy was performed on a GE Signa system. Eleven
      novel homogeneous fat-water phantoms were constructed with variation in fat
      content from 0% to 100%. These were imaged using three techniques and compared
      with single-voxel non-water-suppressed MRS. Pixel-by-pixel maps of fat fraction
      were produced and mean values compared to MRS-determined measurements.
      Preliminary in vivo examinations were subsequently performed in the breast and
      spine to compare the best imaging technique with MRS. RESULTS: All imaging
      methods significantly correlated with MRS (P < 0.001): IDEAL (r(2) = 0.985), IOP
      (r(2) = 0.888), WS (r(2) = 0.939), and FS (r(2) = 0.938). In addition, IDEAL
      provided artifact-free maps of fat fraction with superior uniformity. In vivo
      results using IDEAL produced values that were between 9% to 16% of the
      corresponding MRS values. CONCLUSION: This work demonstrates that imaging may be
      utilized as a high-resolution alternative to MRS for the quantification of fat
      content. In the future we intend to replace MRS with IDEAL in our clinical
      studies involving fat measurement.

PMID- 18064715
TI  - Echo combination to reduce proton resonance frequency (PRF) thermometry errors
      from fat.
AB  - PURPOSE: To validate echo combination as a means to reduce errors caused by fat
      in temperature measurements with the proton resonance frequency (PRF) shift
      method. MATERIALS AND METHODS: Computer simulations were performed to study the
      behavior of temperature measurement errors introduced by fat as a function of
      echo time. Error reduction by combining temperature images acquired at different
      echo times was investigated. For experimental verification, three echoes were
      acquired in a refocused gradient echo acquisition. Temperature images were
      reconstructed with the PRF shift method for the three echoes and then combined in
      a weighted average. Temperature measurement errors in the combined image and the
      individual echoes were compared for pure water and different fractions of fat in
      a computer simulation and for a phantom containing a homogenous mixture with 20%
      fat in an MR experiment. RESULTS: In both simulation and MR measurement, the
      presence of fat caused severe temperature underestimation or overestimation in
      the individual echoes. The errors were substantially reduced after echo
      combination. Residual errors were about 0.3 degrees C for 10% fat and 1 degrees C
      for 20% fat. CONCLUSION: Echo combination substantially reduces temperature
      measurement errors caused by small fractions of fat. This technique then
      eliminates the need for fat suppression in tissues such as the liver.

PMID- 18064716
TI  - State birth defects surveillance program directory.

PMID- 18064717
TI  - Mismatch repair protein expression in Amsterdam II criteria-positive patients in
      Taiwan.
AB  - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is characterized
      genetically by germline mutations in DNA mismatch repair (MMR) genes.
      Immunohistochemistry (IHC) has high sensitivity and specificity for identifying
      MMR-deficient tumours. This study investigated the clinical presentations and
      frequency of HNPCC in Taiwan by combined Amsterdam II criteria (AC-II) and IHC.
      METHODS: In 1995-2003, 7108 patients with primary colorectal cancer registered in
      Chang Gung Memorial Hospital's Colorectal Cancer Registry were screened using AC
      II. Tumour specimens were analysed for MMR protein expression by IHC, and
      relevant clinicopathological details were documented. RESULTS: Some 83 patients
      fulfilled the AC-II. Clinicopathologically, 43 patients (52 per cent) had
      proximal tumours, ten (12 per cent) had poorly differentiated cancers, 17 (20 per
      cent) had mucinous adenocarcinoma and 51 (61 per cent) had stage I-II tumours.
      Seventeen patients developed second primary colonic and extracolonic cancers over
      a mean 7.2-year follow-up. Immunohistochemically, 58 patients were MMR protein
      deficient. They had a significantly earlier age of onset (P < 0.001), more
      proximal tumour location (P = 0.002), less advanced tumour stage (P = 0.008) and
      more second primary cancers (P = 0.017) compared with MMR-competent patients.
      CONCLUSION: These data show significant differences in clinical features between
      MMR protein-deficient and MMR competent subgroups.

PMID- 18064718
TI  - Promoters influence the kinetics of transgene expression following adenovector
      gene delivery.
AB  - BACKGROUND: The kinetics of gene expression from adenovirus-based delivery
      vectors will be an important variable influencing the efficacy and toxicity of
      these vectors. As different promoters have variable strengths and kinetic
      profiles, the optimal dose of a therapeutic transgene product over time may be
      achieved by varying the promoter. METHODS: We analyzed several viral and cellular
      promoters in the context of adenovector gene delivery in the mouse. The kinetics
      of transgene expression was evaluated following intramuscular and intravenous
      delivery. RESULTS: Transgene expression from the cytomegalovirus (CMV) promoter
      was rapidly down-regulated in the tissues following intravenous administration of
      adenovectors. In contrast, transgene expression from the Rous sarcoma virus (RSV)
      promoter increased over time such that, at 3 weeks, expression was 10-fold higher
      than that from the CMV promoter-containing vector in all tissues. The kinetics of
      transgene expression from these vectors was similar when they were delivered via
      the intramuscular route in BALB/c, C57BL/6 and immunodeficient mice. Efficient
      repeat administration of an adenovirus vector, in the presence of neutralizing
      antibodies, was achieved in the skeletal muscle and transgene expression
      persisted with the same kinetics as in naive animals. CONCLUSIONS: These results
      demonstrate that the in vivo kinetics of transgene expression by adenovectors is
      greatly influenced by the promoter. Adenovectors can be designed to deliver a
      transient bolus or a sustained level of protein expression in the target tissue
      depending on the requirements for particular indications. These results have
      implications for both therapeutic and vaccine indications.

PMID- 18064719
TI  - AAV-mediated knockdown of phospholamban leads to improved contractility and
      calcium handling in cardiomyocytes.
AB  - BACKGROUND: Reduced contractility due to dysregulation of intracellular calcium
      (Ca(2+)) is a common pathologic feature of chronic heart failure. Calcium stores
      in the sarcoplasmic reticulum play a major role in regulating cardiac
      contractility. Several animal models of heart failure have been treated by
      altering the regulation of the sarcoplamic reticulum ATPase through ablation or
      down-regulation of its inhibitor peptide, phospholamban (PLN). METHODS: We have
      designed two small hairpin RNAs (shRNAs) to block the synthesis of PLN via RNA
      interference. These were tested in cell culture using a co-transfection assay and
      using adeno-associated virus (AAV)-mediated delivery to cardiomyocytes. Reverse
      transcription polymerase chain reaction (RT-PCR) and Western blots were used to
      measure reduction in PLN mRNA and protein levels. Reduction of PLN was also
      documented by indirect immunofluorescence. Free cytosolic calcium and contractile
      properties of transduced cardiomyocytes was examined on fura-2-loaded cells.
      Direct cardiac injection was used to deliver AAV1-shRNAs to mice, and reduction
      of PLN was measured by indirect immunofluorescence. RESULTS: Both siRNAs led to
      significant reduction of PLN RNA and protein levels in cultured cells. Down
      regulation of PLN led to enhanced cell shortening and relaxation and to a
      decrease in the time constant of calcium decay, signs of improved contractility
      and calcium handling. In the hearts of AAV-infected mice, shRNA-transduced cells
      showed significant reduction in the level of PLN. CONCLUSIONS: Our results
      suggest that AAV-delivered shRNAs mediated physiologically significant
      suppression of phospholamban that may be useful in combating the effects of
      chronic heart failure.

PMID- 18064720
TI  - Effect of oxidative stress on rat thyrocyte iodide metabolism.
AB  - Thyroid cells fall into the type of cells functioning during continuous
      production of high H(2)O(2) concentrations. We studied the effect of H(2)O(2)
      induced oxidative stress (0.1, 1.0 and 10.0 mM) on the activities of the key
      steps of iodide metabolism (uptake, oxidation and organification) in thyrocytes
      cultivated in an organ culture. After 60 min cultivation of cells in a medium
      containing H(2)O(2) at concentrations of 1.0 and 10.0 mM iodide (I(-)) uptake,
      thyroperoxidase (TPO) activity and I(-) organification were completely inhibited.
      No restoration of the parameters studied was observed within the subsequent 24 h
      of cultivation. The inhibitory effect of 0.1 mM H(2)O(2) was reversible.
      Activation of I(-) uptake in the cultivated tissue and a 520-880% increase of the
      total I(-) content were observed after 8 and 24 h. The concentration of I(-)
      protein-bound fraction was raised by 220% after 24 h. A biphasic effect of 0.1 mM
      H(2)O(2) on TPO was observed: 76.2% and 72.2% inhibitions were seen after 2 and 8
      h, respectively, whereas 40.0% enzyme activation was after 5 h. TPO activity was
      partially restored after 24 h and amounted to 65% of the initial value. The
      significant increase in the concentration of iodide protein-bound fraction, which
      was observed simultaneously with TPO inhibition, could be due to thyroglobulin
      non-enzymic iodination under H(2)O(2)-generated oxidative stress. The data
      obtained indicate that iodide oxidation, as a step in the biosynthesis of thyroid
      hormones, was most sensitive to oxidative stress activation. The impaired iodide
      uptake and its organification during oxidative stress can play a pathogenetic
      role in disturbed functions of thyroid cells.

PMID- 18064721
TI  - Carnosine attenuates mast cell degranulation and histamine release induced by
      oxygen-glucose deprivation.
AB  - Carnosine (beta-alanyl-histidine) is a naturally occurring dipeptide that has
      been characterized as a putative hydrophilic antioxidant. The protective function
      of carnosine has been demonstrated in neuronal cells under ischemic injury. The
      purpose of this study was to investigate the effects of carnosine on oxygen
      glucose deprivation (OGD)-induced degranulation and histamine release from mast
      cells. Cultured mast cells were exposed to OGD for 4 h, and then the
      degranulation was observed immediately by microscopy. Histamine release was
      analyzed by high-performance liquid chromatography (HPLC). OGD caused
      degranulation of mast cells, and increased histamine and lactate dehydrogenase
      (LDH) release. Carnosine (at a concentration of 5 mM) alone did not produce any
      appreciable effect on degranulation, histamine, and LDH release from mast cells
      under normal condition, but significantly inhibited the degranulation, histamine,
      and LDH release of mast cells induced by OGD. These results indicate that
      carnosine can protect mast cells from degranulation and histamine release and it
      may be an endogenous mast cell stabilizer in the pathological processes induced
      by ischemia.

PMID- 18064722
TI  - Hepatitis C virus infection in haemodialysis and kidney transplant patients.
AB  - Chronic infection with hepatitis C virus (HCV) is an important global health
      problem. The prevalence of HCV is significantly higher in haemodialysis and
      kidney transplant patients, as compared to the general population. In spite of
      the relatively milder liver disease activity reported in HCV-infected
      haemodialysis patients, HCV infection adversely affects survival. Likewise, HCV
      has a detrimental effect on both patient and graft survival after kidney
      transplantation. However, patient survival is significantly better with kidney
      transplantation compared to remaining on dialysis; therefore, HCV infection alone
      should not be a contraindication to transplantation. Combination antiviral
      therapy with pegylated interferon-alpha and low-dose ribavirin is currently
      evolving in haemodialysis patients. Interferon-alpha (standard/pegylated) is
      relatively contraindicated after kidney transplantation because of an increased
      risk of allograft rejection. Therefore, antiviral treatment of transplant
      candidates while on dialysis remains the best option and may avoid the risk of
      HCV-associated liver and renal disease after transplantation. Large multi-centre
      clinical trials are required in HCV-infected haemodialysis and kidney transplant
      patients in order to define optimal therapeutic strategies before and after
      transplantation.

PMID- 18064727
TI  - Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating
      activity.
AB  - Parkinson's disease is a neurodegenerative disorder for which no neurorestorative
      therapeutic treatment is currently available. Oxidative stress plays an important
      role in the pathophysiology of Parkinson's disease. The ancient Indian medical
      system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's
      disease. In our earlier studies, Mucuna pruriens has been shown to possess
      antiparkinson and neuroprotective effects in animal models of Parkinson's
      disease. The antioxidant activity of Mucuna pruriens was demonstrated by its
      ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species.
      Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose
      sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not
      show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest
      that the neuroprotective and neurorestorative effect of Mucuna pruriens may be
      related to its antioxidant activity independent of the symptomatic effect. In
      addition, the drug appears to be therapeutically safe in the treatment of
      patients with Parkinson's disease.

PMID- 18064728
TI  - Hydrolysis of various bioactive peptides by goat brain dipeptidylpeptidase-III
      homologue.
AB  - DPP-III from goat brain was purified to apparent electrophoretic homogeneity
      which showed several characteristics similar to other reported DPP-IIIs although
      it possesses dissimilar molecular weight and different inhibition behavior. Thin
      layer chromatographic studies with goat brain DPP-III revealed that it hydrolyses
      Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) at the Gly-Gly bond producing Tyr-Gly and
      Gly-Phe-Leu with no further degradation of liberated tripeptide. (Ala)(4) is
      hydrolyzed to dialanine whereas trialanine is not cleaved. ACTH, angiotensin II
      and III were also hydrolyzed whereas angiotensin I was not. It was concluded that
      the enzyme requires at least a tetrapeptide to act and that it removes a
      dipeptidyl moiety from the NH(2)-terminus of the studied peptides. Goat brain DPP
      III may be involved in the metabolism of very important bioactive peptides such
      as enkephalins and angiotensins.

PMID- 18064729
TI  - Highly efficient gene transfer with degradable poly(ester amine) based on
      poly(ethylene glycol) diacrylate and polyethylenimine in vitro and in vivo.
AB  - BACKGROUND: Polyethylenimine (PEI) is toxic although it is one of the most
      successful and widely used gene delivery polymers with the aid of the proton
      sponge effect. Therefore, development of new novel gene delivery carriers having
      high efficiency with less toxicity is necessary. METHODS: In this study, a
      degradable poly(ester amine) carrier based on poly(ethylene glycol) diacrylate
      (PEGDA) and low molecular weight linear PEI was prepared. Furthermore, we
      compared the gene expression of the polymer/DNA complexes using two delivery
      methods: intravenous administration as an invasive method and aerosol as a non
      invasive method. RESULTS: The synthesized polymer had a relatively small
      molecular weight (MW = 7980) with 25 h half-life in vitro. The polymer/DNA
      complexes were formed at an N/P ratio of 9. The particle sizes and zeta
      potentials of the complexes were dependent on N/P ratio. Compared to PEI 25K, the
      newly synthesized polymer exhibited high transfection efficiency with low
      toxicity. Poly(ester amine)-mediated gene expression in the lung and liver was
      higher than that of the conventional PEI carrier. Interestingly, non-invasive
      aerosol delivery induced higher gene expression in all organs compared to
      intravenous method in an in vivo mice study. Such an expressed gene via a single
      aerosol administration in the lung and liver remained unchanged for 7 days.
      CONCLUSIONS: Our study demonstrates that poly(ester amine) may be applied as an
      useful gene carrier.

PMID- 18064730
TI  - Analysis of the intracellular barriers encountered by nonviral gene carriers in a
      model of spatially controlled delivery to neurons.
AB  - BACKGROUND: Neuron-specific, nonviral gene delivery vehicles are useful tools for
      the potential treatment of neurological disease and spinal cord injury. For
      minimally invasive, peripheral administration, gene carriers must efficiently
      mediate uptake at axon terminals, retrograde axonal transport, vesicular escape,
      and nuclear entry. The design of improved vehicles will benefit from an
      understanding of the barriers that limit nonviral delivery to neurons. Here, we
      demonstrate a detailed analysis of intracellular trafficking of both a lipid
      based and a polymer-based delivery vehicle following site-specific exposure to
      neuron-like cells. METHODS: Site-specific exposure of gene carriers to soma or
      neurites of neuron-like PC-12 cells was accomplished using a microfluidic,
      compartmented culture chamber. Binding and internalization of vehicles at
      neurites and soma were quantified using an environmentally sensitive fluorescent
      marker. The intracellular transport of gene carriers was analyzed by time-lapse
      particle tracking in live cells, and transfection efficiencies were measured
      using green fluorescent protein (GFP) as a reporter gene. RESULTS: While the
      lipid-based carrier mediated measurable transfection when delivered to neuronal
      soma, neuritic delivery of this formulation failed to produce reporter gene
      expression due to limited internalization and transport. In contrast, the
      polymeric nanoparticles displayed active retrograde transport toward neuronal
      soma, but failed to produce measurable reporter gene expression. CONCLUSIONS:
      These results highlight distinct intracellular barriers preventing efficient
      neuronal transfection by the nonviral carriers examined, and provide a basis for
      the rational improvement of existing nonviral systems.

PMID- 18064731
TI  - Intrathecal coelectrotransfer of a tetracycline-inducible, three-plasmid-based
      system to achieve tightly regulated antinociceptive gene therapy for
      mononeuropathic rats.
AB  - For optimal use of antinociceptive gene therapy, it may be important to have
      extrinsic control of the expression of the transfected gene. To achieve this
      goal, we used a tetracycline-inducible system (Tet-On) composed of three plasmids
      coding for beta-endorphin, the tetracycline transcriptional activator rtTA, and
      the silencer tTS. The regulation of beta-endorphin expression was first assessed
      in cultures of dorsal root ganglion neurons. The three plasmids were then
      electrotransfected into the spinal cord of mononeuropathic rats and the analgesic
      potential of this therapy in vivo was evaluated by thermal-withdrawal latency and
      the mechanical-withdrawal threshold. Intraperitoneal injections of doxycycline
      were made to evaluate the possibility of exogenous upregulation of transfected
      beta-endorphin gene expression in vivo. The levels of beta-endorphin were
      analyzed by intrathecal microdialysis and radioimmunoassay. We found that, after
      doxycycline administration, the expression of beta-endorphin was rapid, stable,
      and tightly regulated (low background and high induction level) both in vitro and
      in vivo. The beta-endorphin protein was secreted into cerebrospinal fluid at a
      peak level of 53 pmol/L in dialysate, which was sufficient to inhibit neuropathic
      pain. In conclusion, tightly controlled expression of beta-endorphin can be
      obtained following intrathecal electrotransfer of a tetracycline-inducible, three
      plasmid-based system, and doxycycline-dependent beta-endorphin protein expression
      in this system alleviates sciatic nerve constriction-induced limb pain.

PMID- 18064732
TI  - Separation of very hydrophobic analytes by micellar electrokinetic
      chromatography. I. Optimization of the composition of the sample solution for the
      determination of the aromatic ingredients of sassafras and other essential oils
      of forensic interest.
AB  - A micellar electrokinetic chromatographic method using UV and (UV)LIF detection
      in-line was developed for the determination of aromatic constituents, mainly
      allylbenzenes in essential oils. The method optimization included the
      optimization of the composition of the separation electrolyte using ACN and urea
      to reduce retention factors and CaCl(2) to widen the migration time window. In
      addition, it was necessary to optimize the composition of the sample solution
      which included the addition of a neutral surfactant at high concentration. With
      the optimized method, the determination of minor constituents in essential oils
      was possible despite of the presence of a structurally related compound being in
      a molar ratio excess of 1000:1. The use of UV and LIF-detection in-line enabled
      the direct comparison of the two detection traces using an electrophoretic
      mobility x-axis instead of the normal time-based scale. This simplifies the
      assignment of signals and enhances repeatability. The method developed was
      successfully applied to the determination of minor and major constituents in
      herbal essential oils, some of them being forensically relevant as sources of
      precursors for synthetic drugs.

PMID- 18064733
TI  - Fast CE for combinatorial catalysis.
AB  - Two solvent-modified MEKC methods were developed for the quantitative analysis of
      heterocyclic amines synthesised using intramolecular ring closure via catalysed
      hydroamination. The first method was capable of resolving six of the amines
      (precursors and products) with a sample-to-sample injection time of 2 min
      employing a 20 mM borate buffer, pH 9.2 with 20 mM SDS and 5% v/v n-butanol (n
      BuOH). A second low-pH method using 20 mM phosphate buffer, 100 mm SDS, 5% v/v n
      BuOH and 20% v/v iso-propanol (i-PrOH) was able to resolve an additional pair of
      compounds with a sample-to-sample time of 3.5 min. Application of the first
      method to the analysis of a sample containing catalyst as well as amines placed
      directly in a 96-well plate showed excellent performance, with migration time and
      peak height and area reproducibility being less than 0.9 and 9.6%, respectively.
      The quantity of conversion by catalyst was calculated to be 68 +/- 7%, which was
      in excellent agreement with the 67 +/- 5% obtained by more conventional (1)H NMR
      experiments, with the added advantage that this method is also cheaper, quicker
      and more amendable to high-throughput screening of combinatorial libraries.

PMID- 18064734
TI  - Stacking and separation of protein derivatives of naphthalene-2,3
      dicarboxaldehyde by CE with light-emitting diode induced fluorescence detection.
AB  - We describe the stacking and separation of proteins by CE under discontinuous
      conditions in conjunction with light-emitting diode induced fluorescence (LEDIF)
      detection using a violet LED at 405 nm. The proteins were derivatized with
      naphthalene-2,3-dicarboxaldehyde (NDA) to form NDA-protein derivatives prior to
      CE-LEDIF analysis. During the separation, poly(ethylene oxide) (PEO) solution
      containing CTAB enters from the cathodic inlet to the capillary via
      electroosomotic flow (EOF). The optimum conditions are: the capillary was filled
      with 50 mM glycine buffer (pH 9.0) containing 1.0 mM CTAB, NDA-protein
      derivatives were prepared in deionized water containing 1.0 mM CTAB, and 0.6% PEO
      was prepared in 50 mM glycine (pH 9.0) containing 2.0 mM CTAB. The analysis of
      four NDA-protein derivatives is fast (<3 min), with RSD <1.5% in terms of
      migration time. In order to improve the sensitivity of NDA-protein derivatives, a
      stacking approach based on increases in viscosity and electric field, as well as
      sieving was applied. The efficient stacking approach provides LODs (S/N = 3) of
      2.41, 0.59, 0.61, and 4.22 nM for trypsin inhibitor, HSA, beta-lactoglobulin, and
      lysozyme, respectively. In addition, we also applied the stacking approach to
      determination of the concentration of HSA in one urine sample, which was
      determined to be 0.31 +/- 0.05 microM (n = 3).

PMID- 18064735
TI  - Evaluation of band broadening in chemiluminescence detection coupled to
      pressurized capillary electrochromatography with an off-column coaxial flow
      interface.
AB  - A system of off-column coaxial flow chemiluminescence (CL) detection coupled to
      pressurized CEC (pCEC) was described. The interface utilized a reactor that
      introduced postcolumn CL reagent into the capillary effluents in a sheathing flow
      profile. To compare and evaluate band broadening of analytes caused by the
      detector, the typical CL compounds luminol and N-(4-aminobutyl)-N-ethylisoluminol
      (ABEI) were separated and detected by pCEC or capillary HPLC (cHPLC) coupled to
      CL and UV detector, respectively. The results demonstrated that the band
      broadening caused by off-column detection interface was minimized due to the fast
      kinetic nature of the CL reaction. With the proposed pCEC-CL system, the
      detection limits of luminol and ABEI were 1.0x10(-8) and 8.0x10(-8) mol/L,
      respectively, which were approximately 100-fold more sensitive than those
      obtained with UV absorption. In addition, separation and detection of the ABEI
      labeled L-lysine (L-Lys) and L-arginine (L-Arg) were accomplished by pCEC-CL
      method based on the principle of ABEI-potassium ferricyanide-alkaline medium CL
      reaction system. Under the optimum conditions, good results could be achieved
      compared with pCEC-UV.

PMID- 18064736
TI  - Protein extraction from Phoenix dactylifera L. leaves, a recalcitrant material,
      for two-dimensional electrophoresis.
AB  - This work was aimed at optimizing a protein extraction procedure for date palm
      (Phoenix dactylifera L.) leaves, a highly recalcitrant plant tissue for 2-DE.
      Five protein extraction protocols based on different protein precipitation agents
      (TCA/acetone vs. phenol (Ph) methods) and protein resolubilization methods
      (physical treatments, e.g., sonication, shaking and/or heating) were tested.
      Ph/SDS extraction with methanol/ammonium acetate precipitation, followed by DOC
      preincubation and TCA/acetone precipitation and, finally, solubilization by
      shaking in rehydration solution was found to be the best protein extraction
      method. We conclude that DOC with TCA/acetone precipitation step eliminates
      interfering compounds, thus allowing efficient resolubilization of date palm leaf
      proteins. This method could be appropriate for proteomic studies such as date
      palm colonization by entomopathogenic fungi.

PMID- 18064739
TI  - The Strengthening the Reporting of Observational Studies in  Epidemiology
      (STROBE) statement: guidelines for reporting observational studies.
AB  - Much biomedical research is observational. The reporting of such research is
      often inadequate, which hampers the assessment of its strengths and weaknesses
      and of a study's generalisability. The Strengthening the Reporting of
      Observational Studies in Epidemiology (STROBE) initiative developed
      recommendations on what should be included in an accurate and complete report of
      an observational study. We defined the scope of the recommendations to cover
      three main study designs: cohort, case-control, and cross-sectional studies. We
      convened a 2-day workshop in September, 2004, with methodologists, researchers,
      and journal editors to draft a checklist of items. This list was subsequently
      revised during several meetings of the coordinating group and in e-mail
      discussions with the larger group of STROBE contributors, taking into account
      empirical evidence and methodological considerations. The workshop and the
      subsequent iterative process of consultation and revision resulted in a checklist
      of 22 items (the STROBE statement) that relate to the title, abstract,
      introduction, methods, results, and discussion sections of articles.18 items are
      common to all three study designs and four are specific for cohort, case-control,
      or cross-sectional studies.A detailed explanation and elaboration document is
      published separately and is freely available on the websites of PLoS Medicine,
      Annals of Internal Medicine, and Epidemiology. We hope that the STROBE statement
      will contribute to improving the quality of reporting of observational studies

PMID- 18064741
TI  - G-protein-coupled receptors: from molecular aspects to novel therapy. Proceedings
      of the 14th Acta Physiologica International Symposium, 17-18 August 2006,
      Stockholm, Sweden.

PMID- 18064742
TI  - Proceedings of the 5th International Conference on Hypertension and the Kidney,
      February 2006, Madrid, Spain.

PMID- 18064743
TI  - Graves' disease.

PMID- 18064744
TI  - Reconstruction teams work toward stabilizing Iraq.

PMID- 18064745
TI  - Meeting the health needs of Iraqi refugees in Jordan.

PMID- 18064746
TI  - Workforce biggest barrier to roll-out of male circumcision.

PMID- 18064747
TI  - Meningococcal C conjugate vaccination recommendations for infants. An Advisory
      Committee Statement (ACS).

PMID- 18064748
TI  - [Adaptation of work to man].

PMID- 18064749
TI  - [Working despite having diseases: Skin diseases].

PMID- 18064750
TI  - [Anticoagulants. Bridging anticoagulation with interventional techniques].

PMID- 18064751
TI  - Migraine prevalence, diagnosis, and disability.
AB  - The goal of the Canadian Migraine Forum was to work towards improving the lives
      of Canadians with migraine by reducing their migraine-related disability. This
      paper reviews the epidemiology and diagnosis of migraine, and the effects of
      migraine on health related quality of life. Many patients with migraine do not
      consult a physician for their headaches, and when they do they often do not
      receive a correct diagnosis. The discussion at the Forum concluded that better
      education, both for physicians and the public, on issues relating to migraine was
      a necessary step in improving migraine diagnosis. The degree of disability caused
      by migraine is often not recognized by society, and can be substantial for
      individuals with migraine. Once again, education of the public and of the health
      professionals who see these patients is key, so that the best migraine management
      can be instituted to minimize the impact of migraine on the individual, the
      family, and society at large.

PMID- 18064752
TI  - CMS issues new conditions for coverage for ambulatory surgical centers.

PMID- 18064753
TI  - [What is feasible and which training can be recommended. Escaping from the risks
      of old age].

PMID- 18064754
TI  - [When will the artificial pancreas be available? (interview by Dr. med. Jochen
      Aumiller)].

PMID- 18064755
TI  - [About anti-psychiatry and such].

PMID- 18064756
TI  - [Molecular cloning and characteristics of cDNA encoding pig beta6 subunit for
      FMDV receptor].
AB  - In order to study the roles of integrin beta6 in Foot-and-Mouth Disease Virus
      infection, pig integrin beta6 was firstly molecularly cloned from RNA of the
      tongue and lung of recovered pig infected experimentally with foot-and-mouth
      disease virus (FMDV), and was compared with the beta6 gene of other animals
      available in GenBank at nucleotide and amino acid leves. GeneBank association
      number of the beta6 gene is EF432729. Pig integrin beta6 gene (2367bp) encodes a
      polypeptide of 788 amino acids consisting of 9 potential N-linked glycosylation
      sites, 3 Glycosaminoglycan attachment sites, a cGMP-dependent protein kinase
      phosphorylation site, 10 Protein kinase C phosphorylation sites, 2 EGF-like
      domains and 2 cysteine-rich regions. Pig integrin beta6 subunit has a 26-residue
      putative signal peptide, a 681-residue ectodomain, a 29-residue transmembrane
      domain, and a 52-residue cytoplasmic domain. 11 mutant nucleotides were found in
      beta6 gene coding region and 9 amino acids were changed. The nucleotide sequence
      similarity of integrin beta6 gene between rheses monkey, mouse, Norway rat, dog,
      guinea pig, human, bovine, sheep is 79.5%, 84.9%, 85.4%, 85.2%, 88.7%, 90.1%,
      91.9% and 91.9%, and the amino acid sequence similarity is 93.5%, 88.2%, 88.5%,
      88.3%, 91.0%, 92.8%, 93.3% and 93.4% respectively. This study will lay a
      foundation for understanding the interactions of FMDV with receptors.

PMID- 18064757
TI  - Rabies vaccines.   WHO position paper.

PMID- 18064758
TI  - Influenza.

PMID- 18064759
TI  - [Current status and problems in laparoscopic surgery for colorectal cancer].

PMID- 18064760
TI  - [Surgical treatment of rectal neoplasm].

PMID- 18064761
TI  - [Progress of chemotherapy in colorectal cancer].

PMID- 18064762
TI  - Overburdened and overwhelmed: the struggles of communities with high medical cost
      burdens.
AB  - The number of people with potentially high medical cost burdens varies widely
      across the nation, reflecting differences in the number of people who lack health
      insurance coverage and people who have coverage but nevertheless have high costs
      relative to their income. To address this problem, many states are undertaking
      expansions of insurance coverage, but federal support will be critical,
      particularly in states with large numbers of low-income residents.

PMID- 18064763
TI  - Dynamic psychology, utopia, and escape from history: the case of C.G. Jung.

PMID- 18064764
TI  - Early Development of nanoprobes for diagnostic imaging.
AB  - Fluorescence is increasingly used for in vivo imaging and has provided remarkable
      results. Yet this technique presents several limitations, especially due to
      tissue autofluorescence under external illumination and weak tissue penetration
      of low wavelength excitation light. We have developed an alternative optical
      imaging technique by using persistent luminescent nanoparticles suitable for
      small animal imaging. These nanoparticles can be excited before injection, and
      their in vivo distribution can be followed in realtime for more than 1 h without
      the need for any external illumination source. Chemical modification of the
      nanoparticles' surface led to lung or liver targeting or to long-lasting blood
      circulation. Tumor mass could also be identified on a mouse model.

PMID- 18064765
TI  - "Malaria blocks development" revisited: the role of disease in the history of
      agricultural development in the eastern and northern Transvaal Lovweld, 1890
      1960.

PMID- 18064766
TI  - Medicaid integrity program; limitation on contractor liability. Final rule.
AB  - The Medicaid Integrity Program (the Program) provides that the Secretary promote
      the integrity of the Medicaid program by entering into contracts with contractors
      that will review the actions of individuals or entities furnishing items or
      services (whether fee-for-service, risk, or other basis) for which payment may be
      made under an approved State plan and/or any waiver of the plan approved under
      section 1115 of the Social Security Act; audit claims for payment of items or
      services furnished, or administrative services furnished, under a State plan;
      identify overpayments of individuals or entities receiving Federal funds; and
      educate providers of services, managed care entities, beneficiaries, and other
      individuals with respect to payment integrity and quality of care. This final
      rule will provide for limitations on a contractor's liability while performing
      these services under the Program. The final rule will, to the extent possible,
      employ the same or comparable standards and other substantive and procedural
      provisions as are contained in section 1157 (Limitation on Liability) of the
      Social Security Act.

PMID- 18064767
TI  - Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over
      the-counter human use; final rule for over-the-counter antitussive drug products;
      technical amendment. Final rule, technical amendment.
AB  - The Food and Drug Administration (FDA) is amending its regulations (exemption for
      certain drugs limited by new-drug applications to prescription sale, and warning
      and caution statements required by regulations for drugs) by removing the entries
      for carbetapentane citrate. This action is associated with FDA's determination
      that carbetapentane citrate has not been shown to be effective at the over-the
      counter (OTC) doses stated in the exempting regulation. FDA made this
      determination in 1987 as part of its ongoing review of OTC drug products.

PMID- 18064768
TI  - Medical devices; hematology and pathology devices: reclassification of automated
      blood cell separator device operating by centrifugal separation principle. Final
      rule.
AB  - The Food and Drug Administration (FDA) is reclassifying from class III to class
      II the automated blood cell separator device operating by centrifugal separation
      principle and intended for the routine collection of blood and blood components.
      FDA is taking this action on its own initiative based on new information.
      Elsewhere in this issue of the Federal Register, FDA is announcing the
      availability of a guidance document that will serve as the special controls for
      this device, as well as the special controls for the device with the same
      intended use but operating on a filtration separation principle.

PMID- 18064769
TI  - Definition of "positional isomer" as it pertains to the control of schedule I
      controlled substances. Final rule.
AB  - On May 25, 2006, DEA published a Notice of Proposed Rulemaking which proposed the
      addition of a specific definition for the term "positional isomer" to allow for
      the systematic determination of which isomers of schedule I substances would be
      considered to be "positional," and therefore, subject to schedule I control. This
      rulemaking finalizes that definition. The Controlled Substances Act (CSA) and its
      implementing regulations specify which hallucinogenic substances are considered
      schedule I controlled substances. The CSA states that all salts, isomers, and
      salts of isomers of these substances are also schedule I controlled substances.
      In non-technical terms, an isomer of a substance is a different compound, but a
      compound which has the same number and kind of atoms. The terms "optical isomer"
      and "geometric isomer" are specific scientific terms and it is easy to determine
      whether one substance is an optical or geometric isomer of another. The term
      "positional isomer," however, is subject to scientific interpretation. The
      addition of a definition for the term "positional isomer" will assist legitimate
      research[ers] and industry in determining the control status of materials that
      are "positional isomers" of schedule I hallucinogens. While the DEA will remain
      the authority for ultimately determining the control status of a given material,
      providing a specific definition for "positional isomer" will ensure consistent
      criteria are utilized in making these determinations. This rule does not change
      existing laws, regulations, policies, processes, and procedures regarding the
      determination of control status for schedule I hallucinogenic substances. This
      rule merely makes available to the public the longstanding definition of
      "positional isomer" which DEA has used when making these scheduling
      determinations. This rule is relevant only to specialized forensic or research
      chemists. Most of these individuals are existing DEA registrants who are
      authorized by the DEA to handle schedule I hallucinogenic substances.

PMID- 18064770
TI  - Amendment to the current good manufacturing practice regulations for finished
      pharmaceuticals. Direct final rule.
AB  - The Food and Drug Administration (FDA) is amending certain regulations as the
      first phase of an incremental approach to modifying the current good
      manufacturing practice (CGMP) regulations for finished pharmaceuticals. We are
      amending the regulations to modernize or clarify some of the CGMP requirements,
      as well as harmonize some of the CGMP requirements with those of other foreign
      regulators and other FDA regulations. These amendments are also consistent with
      current industry practice. We are taking this action as part of our continuing
      effort to revise outdated regulations without diminishing public health
      protection. We are issuing a direct final rule for this action because FDA
      expects there will be no significant adverse comments on these amendments.
      Elsewhere in this issue of the Federal Register, we are publishing a companion
      proposed rule, under our usual notice-and-comment rulemaking procedures, to
      provide a procedural framework to finalize the rule in the event the agency
      receives any significant adverse comments and withdraws this direct final rule.
      The companion proposed rule and direct final rule are substantively identical.

PMID- 18064771
TI  - Reasonable charges for medical care or services. Final rule.
AB  - This final rule amends the Department of Veterans Affairs (VA) medical
      regulations concerning "reasonable charges" for medical care or services provided
      or furnished by VA to certain veterans for nonservice-connected disabilities. It
      changes the process for determining interim billing charges when a new Diagnosis
      Related Group (DRG) code or Current Procedural Terminology/Healthcare Common
      Procedure Coding System (CPT/HCPCS) code identifier is assigned to a particular
      type or item of medical care or service and VA has not yet established a charge
      for the new identifier. This process is designed to provide interim billing
      charges that are very close to what the new billing charges would be when the
      charges for the new identifiers are established in accordance with the
      regulations. This final rule also changes the regulations by removing all of the
      provisions for discounts of billed charges. This will eliminate or reduce
      duplicate discounting and thereby prevent unintended underpayments to the
      government.

PMID- 18064772
TI  - Extension of the presumptive period for compensation for Gulf War veterans. Final
      rule.
AB  - This document affirms an amendment to the Department of Veterans Affairs (VA)
      adjudication regulation regarding compensation for disabilities resulting from
      undiagnosed illnesses suffered by veterans who served in the Persian Gulf War.
      This amendment is necessary to extend the presumptive period for qualifying
      chronic disabilities resulting from undiagnosed illnesses that must become
      manifest to a compensable degree in order that entitlement for compensation be
      established. The intended effect of this amendment is to provide consistency in
      VA adjudication policy and preserve certain rights afforded to Persian Gulf War
      veterans and ensure fairness for current and future Persian Gulf War veterans.

PMID- 18064773
TI  - Medicare program; revisions to the Medicare Advantage and Part D prescription
      drug contract determinations, appeals, and intermediate sanctions processes.
      Final rule with comment period.
AB  - This rule with comment period finalizes the Medicare program provisions relating
      to contract determinations involving Medicare Advantage (MA) organizations and
      Medicare Part D prescription drug plan sponsors, including eliminating the
      reconsideration process for review of contract determinations, revising the
      provisions related to appeals of contract determinations, and clarifying the
      process for MA organizations and Part D plan sponsors to complete corrective
      action plans. In this final rule with comment period, we also clarify the
      intermediate sanction and civil money penalty (CMP) provisions that apply to MA
      organizations and Medicare Part D prescription drug plan sponsors, modify
      elements of their compliance plans, retain voluntary self-reporting for Part D
      sponsors and implement a voluntary self-reporting recommendation for MA
      organizations, and revise provisions to ensure HHS has access to the books and
      records of MA organizations and Part D plan sponsors' first tier, downstream, and
      related entities. Although we have decided not to finalize the mandatory self
      reporting provisions that we proposed, CMS remains committed to adopting a
      mandatory self-reporting requirement. To that end, we are requesting comments
      that will assist CMS in crafting a future proposed regulation for a mandatory
      self-reporting requirement.

PMID- 18064774
TI  - Rethinking ancestors and colonial power in Madagascar.

PMID- 18064775
TI  - [Demented or demon-possessed? Exorcism and the psychic sciences, 19th and 20th
      centuries].

PMID- 18064776
TI  - [Kinship and production: the social organization of agricultural export in the
      province of Limon, Costa Rica, 1920-60].

PMID- 18064777
TI  - Discipline, subjectivity and personality: an analysis of the manuals of four
      psychological tests.

PMID- 18064778
TI  - "For mothers only": mothers' convalescent homes and modernizing maternal ideology
      in 1950s West Germany.

PMID- 18064779
TI  - Gender and working class identity in Britain during the 1950s.

PMID- 18064780
TI  - Designing families and solid citizens: the dialectic of modernity and the
      Matrimonial Causes Bill, 1959.
AB  - Policy-makers in the 1940s and 50s were intent on designing families which would
      produce solid citizens to engage in nation building. Historians offamilism treat
      it as an expression of modernism: a unifying, oppressive discourse now to be
      countered by the destabilising project of postmodernism. But this is not the
      whole story, for it omits the dialectical essence of 'the modern', which promises
      both 'progress' through technical rationality and individual achievement/self
      fulfilment. The other side of the dialectic has been avoided by dismissing
      individualism as a process of interpellation closely tied to the interests of
      technocratic elites. Out of the discontinuities within modernism there emerged
      opportunities for agency, the chance for people to make their own lives. The
      public controversy over the Matrimonial Causes Bill, 1959-at the height of what
      we are encouraged to think of as the familist decade-is explored as one instance.

PMID- 18064782
TI  - [Metabolism of heme and novel drug design].

PMID- 18064781
TI  - Literature and the arts in medical education. STFM 2007 prose contest winners.

PMID- 18064783
TI  - Evaluation of Sterilox for controlling microbial biofilm contamination of dental
      water.
AB  - The purpose of the investigation was to evaluate the effectiveness of Sterilox, a
      sterilizing unit that produces a hydrochlorous acid solution that controls
      microbial contamination as well as reduces biofilms and endotoxin in dental unit
      waterlines (DUWLs). A total of 15 dental units were used: 10 in the Sterilox
      group and 5 in the control group (treatment with Bio2000). Distilled water was
      used as source water. Samples were collected at the baseline, 1-day, and 1, 2, 4,
      and 8 weeks. A scanning electron microscope was used to evaluate the biofilm in
      dental tubing before and after the treatment. The content of endotoxin was
      analyzed using the Chromogenic Limulus Method. The baseline CFU revealed high
      microbial counts (> 39,000 CFU/mL) in all DUWLs. After the treatment and
      throughout the study, the Sterilox practically eliminated the CFU in the
      waterlines, while the control group remained at high CFU counts similar to the
      baseline values. The differences between the 2 groups were significant (P < .05).
      The endotoxin analysis of the DUWL samples indicated that the average amount of
      endotoxin per milliliter increased immediately after the Sterilox shock
      treatment, indicating the lysis of gram-negative bacteria. Endotoxin content then
      quickly declined and remained at an acceptable level throughout the study
      Endotoxin in controls fluctuated in higher levels. It was concluded that Sterilox
      is effective at controlling microbial contamination and reducing biofilms and
      endotoxin in DUWLs.

PMID- 18064784
TI  - Instrument cassettes for office safety and infection control.
AB  - The goal of a dental infection control program is to provide a safe working
      environment that will reduce the risk of health care-associated infections among
      patients and occupational exposures among staff members. Minimizing the potential
      for percutaneous sharps injuries is a primary focus for a comprehensive infection
      control program. This article will review the advantages of using instrument
      cassettes, as well as provide an overview of engineering and work practice
      controls and instrument processing, to emphasize how appropriate use of
      instrument cassettes can improve office safety and infection control.

PMID- 18064785
TI  - Fixed and removable provisional options for patients undergoing implant
      treatment.
AB  - The provisional phase of treatment can be the most challenging aspect of implant
      dentistry. The techniques available today include removable, tooth-supported, and
      implant-retained provisional restorations. The selection of the type of
      provisional prosthesis should be based on esthetic demands, functional
      requirements, duration, and ease of fabrication. This article includes a review
      of 118 articles from peer-reviewed journals published in English from January
      1986 to February 2007. This review was performed using MEDLINE. The indications,
      advantages, and disadvantages of the various provisional restorations are
      discussed.

PMID- 18064786
TI  - Ridge preservation and augmentation using regenerative materials to enhance
      implant predictability and esthetics.
AB  - Dentistry has entered an era in which patients no longer need to accept an
      edentulous or partially edentulous condition, or one in which their candidacy for
      tooth structure replacement (ie, implants with subsequent restoration) must be
      dismissed because of insufficient alveolar bone volume, height, or width. The
      supporting bone can be preserved at the time of tooth extraction, or augmented at
      the time of case presentation, using a variety of available regenerative
      materials. Among them are mineralized human allograft bone and collagen membranes
      that can be placed in combination with specific growth factor complexes and
      implant designs. This article reviews the challenges associated with adequately
      preserving or augmenting the alveolar bone after tooth extraction or loss and
      before implant placement. The research and benefits to support using allogenic
      bone graft and membrane materials for such procedures are detailed, and 3
      clinical cases are presented to demonstrate the clinically successful
      incorporation of these materials with the host tissues.

PMID- 18064787
TI  - 10 techniques for becoming an outstanding leader.
AB  - These 10 action steps can help you become a superior leader. Don't think of
      leadership as a genetic trait, but as a skill you can acquire through focus,
      education, and experience. One suggestion we make in Levin Group seminars is to
      select a single leadership trait each week for the next 10 weeks and use it in
      day-to-day activities. Pursue each leadership trait gradually and it will become
      engrained and contribute to the creation of a superior, high-performance team.

PMID- 18064788
TI  - [Endovascular treatment of carotid artery stenosis with cerebral protection: 5
      year experience].
AB  - BACKGROUND: Percutaneous transluminal angioplasty and stenting with cerebral
      protection is a minimally invasive method for carotid artery stenosis treatment,
      which may be an alternative to surgical endarterectomy. The aim of our study is
      to evaluate results of endovascular treatment in patients at high risk of
      endarterectomy. PATIENTS AND METHODS: Between years 2001-2006, 210 carotid artery
      stenoses in 204 patients were treated in our department. Fourty seven percent of
      patients suffered from symptomatic stenosis, asymptomatic stenosis was proved in
      53% of patients. All asymptomatic patients had stenosis more than 70% measured
      according to NASCET, mostly with contralateral carotid artery occlusion. RESULTS:
      The procedure was technically successful in 99% of patients, mortality was 0.49%.
      Periprocedural embolic complications based on transient ischemic attack were
      observed in 2.39% of patients, symptoms of minor stroke in 0.47% and symptoms of
      major stroke in 0.47% of patients. The mortality and disabled morbidity rate in
      the whole group was 0.96%. One hundred and fifty three patients (73%) were
      followed up, during this time, 7 patients (3.9%) developed hemodynamically
      significant restenosis. CONCLUSION: Endovascular carotid artery stenosis
      treatment with cerebral protection seems to be a safe method of treatment with
      acceptable short-term results. However, long-term follow-up is needed to get
      enough data about safety and effectiveness of this method compared to
      endarterectomy and best medical therapy.

PMID- 18064789
TI  - [Treatment of vascular prosthesis infection and aorto-enteric fistula as a late
      complication after reconstructive surgery of the abdominal aorta--a case report].
AB  - Vascular prosthesis infection is a serious diagnostic and therapeutic problem.
      Timely diagnosis and adequate treatment are essential for the patient's future
      condition. We present a case report of a 60-year-old man with aortobifemoral
      prosthesis infection and with an aortoduodenal fistula. The prosthesis infection
      was confirmed by fluorodeoxyglucose positron emission tomography. Urgent surgery
      was indicated due to massive gastrointestinal bleeding. Because of lower limb
      Ischaemia after removal of the infected bifurcation prosthesis, an implantation
      of an axillobifemoral bypass was performed in a one stage procedure. 8 months
      after the surgery, the patient is in good condition without walking limitation.

PMID- 18064790
TI  - [Biliary ileus--a rare complication of cholecystolithiasis].
AB  - The diagnosis of ileus caused by biliary stones occurs very rarely, with the
      range of 2 % worldwide. This complication of cholecystolithiasis caused by the
      stone fistulation into gastrointestinal tract and its subsequent obstruction
      occurs mostly in elderly and has a high mortality rate. During the course of ten
      years (1996-2006) in the 2nd surgical clinic FNLP in Kosice, 1640
      cholecystectomies and 255 operations, due to the obstruction ileus, were
      performed. Biliary ileus was recorded in four cases. In two cases, the reason
      being an obstruction caused by a travelled stone into jejunum, one event was
      caused by a mechanic wedge of a stone in duodenum and in the last event
      rectosigma was obturated. The diagnostic is relatively difficult because of a
      nonspecific symptomatology and often negative anamnesis of previous problems with
      gallstones. According to literature, the most reliable diagnostic method is
      computer tomography (CT). In our case, abdominal ultrasonography was successful,
      which pointed out this diagnosis. Gastroscopy localized the place of obstruction,
      but not its cause and X-ray image showed aerobilia two times. By the use of
      magnetic resonance cholangiopancreatography (MRCP) the diagnosis was not
      positively confirmed. Only in one out of four cases, there was a suspicion of the
      diagnosis of the biliary ileus, which makes its detectability 25%. The aim of
      this retrospective analysis is the comparison of diagnostic method-options and
      their range of success in the diagnosis of acute abdomen in our clinic and the
      entries in the world literature.

PMID- 18064791
TI  - [The role of interstitial brachytherapy in multimodality management of solid
      tumors].
AB  - Although being used for several decades, interstitial brachytherapy remains a
      modern radiotherapeutic method. Over the time, it has been highly improved,
      including the latest technologies. Its broad use has been facilitaed by the use
      of high dose rate (HDR) afterloadings. The method is fast and fairly inexpensive.
      Its prons include, in particular, a possibility to apply a dose, in addition to
      external radiotherapy, directly into the tumor region or its focus, which may
      improve treatment success rates in patients with localized tumors. The commonest
      diagnoses, where interstitial brachytherapy is employed, include the following:
      breast carcinomas, soft tissue sarcomas, head and neck tumors, gynaecological
      tumors, penile and anal tumors and prostate tumors. In the article, the authors
      aimed to highlight potential and benefits of intersitital brachytherapy in
      individaual diagnoses. Only multidisciplinary management of these patients may
      improve their prognosis or quality of life.

PMID- 18064792
TI  - [Surgical treatment of breast cancer in the Masaryk Memorial Cancer Institute].
AB  - Breast cancer represents the most frequent malignancy in women in the Czech
      Republic. Although surgery plays the basic role in the therapy of its early
      stages there hasn't existed any specialized training in surgical oncology in our
      country so far. Majority of patients are surgically treated at departments of
      general surgery where sometimes outdated procedures are used as we know from our
      own experience. In the Masaryk Memorial Cancer Institute we perform approximately
      500 breast surgeries a year and provide a team of surgeons specialised in this
      field. The aim of our article is to give a basic review of modern techniques in
      breast cancer surgery, to describe more precisely the most frequent ones and to
      give a list of some relevant literary sources.

PMID- 18064793
TI  - [Tumorous stem cells--a novel view in oncology?].
AB  - Authors present contemporary knowledges, arguments and hypothesis about cancer
      STEM cells and their relations to current concepts of oncology and surgical
      oncology. The aim is to introduce new view of carcinogenesis and origin of
      metastatical process as a diseas of STEM cells to general surgical public that
      deal with surgical oncology and is confronted with new trends in modern
      oncological pharmacology. The presented theory of tumour origin by cancer STEM
      cells is confronted critically with all current theories.

PMID- 18064794
TI  - [New treatment approach in liver metastates: hand-assisted laparoscopic
      radiofrequency liver resection].
AB  - BACKGROUND: Hand-assisted laparoscopic liver surgery, a newly developed technique
      based on an innovative concept, has proved useful and safe for a variety of less
      invasive hepatectomies. Radiofrequency assisted hepatic resection has been
      reported to be safe, associated with minimal morbidity and mortality and
      decreased intraoperative blood loss and transfusion requirements. METHOD: We
      describe how we perform hand assisted laparoscopic radiofrequency assisted
      hepatic resection using a bipolar radiofrequency device. RESULTS: The use of the
      hand port has allowed the surgeon to use his hand in direct liver manipulation,
      mobilization, and retraction. It was also useful for tactile tumor localization.
      Radiofrequency assisted hepatic parenchymal transaction was performed using
      bipolar device (Habib 4X) with minimal blood loss (35 ml), and reduced operative
      and resection times (75 min, 17 min respectively). CONCLUSION: This combined
      procedure seems to offer a safer, more effective, and less time-consuming means
      of resection of hepatic tumours. This might encourage surgeons to perform more
      frequently a laparoscopic approach for liver resection.

PMID- 18064795
TI  - [Autofluorescence videothoracoscopy--our initial experience].
AB  - The authors present their initial clinical experience with the use of
      autofluorescence videothoracoscopy in diagnostics of pleural disorders. The study
      used Richard Wolf DAFE fluorescence endoscopy system. Preliminary results show
      that autofluoresence imaging is more precise in locating the pathology, which
      improved the diagnostic yield of videothoracoscopy in pleural disorders. The
      resulting indirect autofluorescence image depicts healthy tissues in a white
      green colour, while tissues with a roughened surface, resulting from hyperplastic
      inflammatory processes (pachypleura, adhesions) and tumorous or dysplastic
      processes, are depicted as vivid blue high-density foci.

PMID- 18064796
TI  - [Interdisciplinary approach to treatment of multiple arterial aneurysms in
      patient with eighth recurrence of incisional hernia--a case report].
AB  - Vascular surgery is not the only option for arterial aneurysm treatment.
      Minimally invasive techniques are being increasingly used, especially methods of
      interventional radiology. We present a case of a 51-year-old man who came to our
      department in July 2005 because of sonographically diagnosed popliteal artery
      aneurysm. Simultaneous presence of subrenal abdominal aortic aneurysm, bilateral
      iliac and femoral artery aneurysms and left popliteal artery aneurysm was found.
      This patient was operated on for pancreatic pseudocyst in 2000 and then during
      next three years eight times for incisional hernia and its recurrences. The
      operations were carried out in other surgical departments. Eighth recurrence of
      incisional hernia was already present. Because of these facts, the risk of
      resection was deemed too high. Therefore, we chose stent graft implantation for
      abdominal aortic aneurysm treatment. The endovascular approach was also used to
      treat some complications that occurred. In this case report, we would like to
      present a combination of surgical and interventional radiological approaches to
      treatment of arterial aneurysms as a typical example of interdisciplinary
      cooperation.

PMID- 18064797
TI  - [Clinically important beta-lactamases of gram-negative bacteria: AmpC].
AB  - Beta-lactamases are the most common cause of beta-lactam resistance in Gram
      negative bacteria. With third-generation and fourth-generation cephalosporins
      being introduced into practice, new beta-lactamases have evolved, able to
      hydrolyze these antibiotics. AmpC-type beta lactamases (cephalosporinases) are
      serine enzymes with the ability to hydrolyze penicillins, monobactams and
      cephalosporins of all generations, including cephamycins. Over the last two
      decades, transferable plasmid-mediated class C beta-lactamases have been reported
      with increasing frequency. The genes for resistance to other groups of
      antibiotics are usually carried on the same mobile element as the AmpC genes. A
      reliable method for AmpC detection in routine diagnosis has not been available
      yet. The issue of AmpC-type beta lactamases is summarized, including their
      identification, interpretation of susceptibility test results and recommended
      treatment of infection caused by AmpC producers.

PMID- 18064798
TI  - [A simultaneous detection of Chlamydia pneumoniae and Chlamydia trachomatis DNA
      by real-time PCR].
AB  - STUDY OBJECTIVE: Design and validation of a real-time PCR assay for quantitative
      detection of C. pneumoniae and C. trachomatis in clinical specimens. MATERIAL AND
      METHODS: A part of the 16S RNA gene was selected as the target sequence for
      amplification. The reaction product was cloned in the bacterial plasmid and a
      recombinant calibrator and a combined internal standard were prepared, usable in
      three different PCR assays. Archived DNA isolates from various clinical
      specimens, DNA isolates from other infectious agents and control samples for DNA
      detection, CT (QCMD) and CPN (Instand), were used for validation. RESULTS:
      Reaction specificity and reproducibility were tested. The analytical sensitivity
      was set to 5-10 copies of the bacterial genome/reaction. As many as 105 DNA
      isolates from various types of clinical specimens (swabs, urine, peripheral blood
      and BAL fluid) were tested by real-time PCR and conventional PCR assays. The
      specimens that had not yielded concordant results were characterized by a third
      independent amplification test. The sensitivity and specificity of real-time PCR
      were 89% and 100%, respectively. The assay is suitable for both screening and
      diagnosis of Chlamydia.

PMID- 18064799
TI  - [Epidemiology of the metabolic syndrome and possibility for its prevention by
      physical activities].
AB  - An epidemiological review of the metabolic syndrome is presented. Focus is on
      history of the discovery of the metabolic syndrome, its definition and changes
      made to it, etiopathogenesis, incidence and possibility for its prevention by
      physical activities.

PMID- 18064800
TI  - [Biofilm formation and response to oxidative stress in Pseudomonas aeruginosa and
      Vibrio cholerae non-O1 depending on culture media].
AB  - OBJECTIVE: To evaluate the effect of six culture media (five complex and one
      mineral) on biofilm formation and response to oxidative stress in Pseudomonas
      aeruginosa (3 strains) and Vibrio cholerae non-O1 (3 strains). METHODS: Biofilm
      formation was quantitatively determined by a crystal violet absorption assay. The
      bacterial response to oxidative stress evoked by hydrogen peroxide was visualized
      as a zone of clearing around the disc after 24 h incubation at 37 degrees C.
      RESULTS: For both of the bacterial species studied, biofilm formation was the
      highest after cultivation in tryptone soya broth (TSM) or in TSM supplemented
      with 8% glucose (TSM+GL), being the lowest in mineral medium (MM). V. cholerae
      non O1 strains were 1.4 to 4.3 times more responsive on average to oxidative
      stress depending on culture medium as compared with P. aeruginosa strains. The
      culture medium had no significant effect on H2O2 evoked by response to oxidative
      stress in vibrios in contrast to P. aeruginosa. In P. aeruginosa, the highest
      mean resistance to H2O2 was observed after cultivation in peptone water while the
      most sensitive cells were found after incubation in TSM+GL and MM. CONCLUSION:
      The culture medium composition influnced biofilm formation in both of the
      bacterial species tested and had a considerable effect on response to oxidative
      stress in P. aeruginosa.

PMID- 18064801
TI  - [Oxidative stress and its role in respiratory diseases].
AB  - Insufficient elimination of free radicals can induce a number of harmful effects
      including a damage of important molecules, injury of genetic information and
      failure of the control and regulatory processes, and even may contribute to
      malignancy. Free radicals probably participate in various respiratory diseases
      (e.g. adult respiratory distress syndrome, chronic obstructive pulmonary disease,
      chronic bronchitis, asthma). Antioxidants, as substances neutralizing effect of
      free radical, contribute to the protection of organism. Both many exogenous
      substances, e.g. enzymes, and exogenous substances, e.g. vitamins and some
      medicaments, have antioxidant properties. An efficacious supplementation is
      conditioned by an appropriate knowledge of health state and of needs of organism
      and also by understanding of the oxidative-antioxidative system and its
      equilibrium.

PMID- 18064802
TI  - [Cytochrome P450 3A polymorphism and its importance in cyclosporine and
      tacrolimus therapy in transplanted patients].
AB  - The calcineurin inhibitors cyclosporine (CsA) and tacrolimus (Tac) are widely
      used in the prevention of acute rejection after solid organ transplantation.
      However, their clinical use is associated with many adverse reactions. The
      calcineurin inhibitors CsA and Tac have a narrow therapeutic index and show
      highly variable pharmacokinetics. The low CsA and Tac bioavailability has been
      attributed to interindividual differences in the expression of the metabolizing
      enzyme cytochrome P450 3A. The genes for CYP3A4 and 3A5 undergo genetic
      polymorphism. The results of many studies focusing on the impact of CYP 3A
      polymorphism on CsA and Tac pharmacokinetics are clear with Tac, where an
      association between CYP 3A polymorphism and the pharmacokinetic consequences has
      been shown. However, the results with CsA are controversial.

PMID- 18064803
TI  - Abiotic elicitation of Trifolium pratense L. suspension culture.
AB  - Important substances of secondary metabolism include flavonoids and
      isoflavonoids. The Trifolium pratense L. (Fabacae) suspension culture is
      characterized by low production of these metabolites and therefore we tried to
      influence the production output with elicitation. From their origin point of
      view, the elicitors are divided into two groups - biotic and abiotic. The latter
      group includes, for instance, the salts of heavy metals. Our work was aimed at
      observing the effect of the copper sulphate abiotic elicitor on the production of
      the Trifolium pratense L. suspension culture (variety DO-8 and variety DO-9) that
      was cultivated in Gamborg media supplemented with 2 mg l(-1) of 2,4
      dichlorophenoxyacetic acid and 2 mg l(-1) of 6-benzylaminopurine. The maximum
      increase in the flavonoid production took place, when compared with the test
      check, during the 168-hour application of the 100 micromol concentration. The DO
      8 variety isoflavonoids production was stimulated namely during the 48-hour
      application of the I micromol concentration; the best elicitation effect of the
      DO-9 variety was achieved with the 168-hour application of the 10 micromol
      concentration.

PMID- 18064804
TI  - [Effect of vanadium compounds on the growth and production of coumarins in the
      suspension culture of Angelica archangelica L].
AB  - Plant tissue cultures represent a promising source of substances of natural
      origin. The main problem of their use is a low production of the majority of
      secondary metabolites. One of the methods of increasing the production of these
      substances is elicitation, because the biosynthesis of many secondary metabolites
      in plant cells is part of the defensive reaction against biological or abiotic
      stress influences. The paper tested vanadium compounds as potential elicitors of
      the production of coumarins: sodium vanadate (0.2; 1; 10; 100 and 1000 microM/l
      of medium) and vanadyl sulfate (10; 20; 50; 100; 200 and 500 microM/l of medium).
      The toxicity of these substances for the culture was simultaneously monitored by
      means of the evaluation of the effects on growth (characterized by fresh and dry
      weights of biomass at the end of two-week cultivation). The cultures were grown
      both in the light and dark. The growth of the cultures was not influenced by
      sodium vanadate at concentrations of 0.2 to 100 microM. A vanadate concentration
      of 1000 microM acted already toxically (in comparison with the control culture,
      the fresh weight was decreased by 28 % and the dry weight by 41% when cultivated
      in the light; the fresh weight by 69% and the dry weight by 66% when cultivated
      in the dark). Vanadyl sulfate in concentrations of 10 to 50 microM did not affect
      the growth of the culture, at higher concentrations it decreased it gradually: a
      concentration of 500 microM acted already toxically, again more markedly when
      cultivated in the light (in comparison with the control culture, the fresh weight
      was decreased by 27% and dry weight by 38% when cultivated in the light; the
      fresh weight by 65% and the dry weight by 61% when cultivated in the dark). The
      production of coumarins was stimulated by sodium vanadate in a concentration of
      0.2 and 1 microM when cultivated in the light. The content of coumarins increased
      in comparison with the control culture mainly in the medium by 46% and by 25% at
      vanadate concentrations of 0.2 and 1 microM, respectively. Vanadyl sulfate did
      not increase the production of coumarins.

PMID- 18064805
TI  - [Effect of thermal curing of the ethyl cellulose film on the rapidity of release
      of diclofenac sodium from pellets].
AB  - Coated pellets controlling drug release are a very popular dosage form which is
      widely used in medical practice. At present the coatings of water-insoluble
      polymers formed from aqueous dispersions are preferred. However, film formation
      from an aqueous polymeric dispersion is different from that from their organic
      solutions. A stable film on the pellets surface is produced by coalesces of
      discrete latex particles at an optimum temperature. The present experimental
      paper studied the changes of diclofenac sodium dissolution profiles from coated
      pellets, when their coatings from an aqueous polymeric dispersion of ethyl
      cellulose were cured for different time periods (1-72 hours) and a temperature of
      60 degrees C. Drug release rate was decreasing with the increasing time of the
      layer curing up to 24 hours. At this time the dissolution curve was similar to a
      strait line. When the curing time further increased, the drug release was again
      faster. All prepared samples (with or without seal coat, cured for a period of 24
      hour or uncured) were filled into hard gelatine capsules and stored in blisters
      in three different stability boxes (25 degrees C/60% RH, 30 degrees C/65% RH, 40
      degrees C/75% RH) for 6 or 12 months. The best drug dissolution profile and
      stability were observed for the pellets with the seal coat and ethyl cellulose
      coating cured for 24 hours.

PMID- 18064806
TI  - [Mucoadhesive tablets for oral administration of ciclopiroxolamine].
AB  - Oral mucoadhesive tablets belong to modern dosage forms, which allow controlled
      drug release after buccal application. They are used for the treatment of oral
      cavity disorders or for systemic administration of drugs with high first-pass
      effect or drugs instable in gastrointestinal tract. This study reports the
      development of oral mucoadhesive tablets containing antimycotic drug
      ciclopiroxolamine. Mucoadhesive properties of placebo tablets containing
      different ratios of carbomer and hydroxypropylmethylcellulose were evaluated in
      vivo in healthy human volunteers. The longest mucoadhesion for 9 hours was
      achieved in matrices containing 60% (w/w) of carbomer. When optimum combination
      of the two mucoadhesive polymers was selected, tablets containing
      ciclopiroxolamine were prepared and one tablet side was film-coated to make the
      application procedure easier. Tablet quality parameters were determined and drug
      dissolution profile was evaluated under different pH conditions. In vitro release
      of ciclopiroxolamine was slower than the desintegration of prepared mucoadhesive
      tablets in vivo. Nevertheless, tablets containing 25 mg of ciclopiroxolamine
      performed prolonged drug release with oral mucosa concentrations higher than its
      MIC of relevant pathogens.

PMID- 18064807
TI  - [Determination of valproic acid by on-line coupled capillary isotachophoresis
      with capillary zone electrophoresis with conductometric detection].
AB  - The paper aimed to test suitable conditions for the determination of VPA in serum
      using the ITP-CZE method with conductometric detection. It attempted to find
      whether for the method described by Olvecka et al. it is possible to use a
      similar procedure of sample preparation as for the gas chromatographic method
      which is routinely employed for the assessment of VPA in serum. A 200 rl sample
      of serum was extracted with 200 rl of acetone and after centrifugation 200 rl of
      the upper layer was withdrawn and supplemented with demineralized water to make
      10 ml. When a microsyringe is used for dosing, consumptions of serum can be
      reduced up to 5 rl, which is advantageous mainly for therapeutic drug monitoring
      in children. The length of analysis was 20 minutes. The method was linear within
      the range of 20-400 mg/l, which includes the therapeutic range of VPA (50-100
      mg/l). The detection and quantification limits were 2.5 and 8.5 mg/l,
      respectively. The variation coefficients were below 10% in all three
      concentrations (30, 70 and 120 mg/l). The new method was compared with the method
      of gas chromatography by means of the Passing-Bablok regression analysis and both
      methods were found to give identical results.

PMID- 18064808
TI  - [Patient advised not to speak].

PMID- 18064809
TI  - [2: General provisions. Observe new game rules!].

PMID- 18064810
TI  - [Family physician EMB. Insurance case reimbursement advantageous for large
      practices].

PMID- 18064811
TI  - [Morbidity differences regulated by additional reimbursement].

PMID- 18064812
TI  - [Child with school problems. Why the family physician is also consulted].

PMID- 18064813
TI  - [Diagnosis and treatment of localized developmental disturbances].
AB  - Localized developmental disturbances of school skills such as dyslexia, acalculia
      and speech and language disorders are common child and adolescent psychiatric
      disorders. Every second child develops comorbid mental disorders such as
      disturbance of social behaviour and hyperkinetic, emotional, anxiety or obsessive
      compulsive disorder. For this reason, a multidisciplinary strategy for the early
      detection, diagnosis and therapy is important.

PMID- 18064814
TI  - [School problems in gifted children and adolescents].
AB  - Parents and teachers must be heedful of children with above-average talents.
      Typical behavioural patterns of very intelligent children must not lead to a lack
      of understanding and rejection. The abilities of these children must be
      encouraged in a sustained manner even at primary school age so that their special
      talents do not develop into resignation or physical or mental disturbances.

PMID- 18064815
TI  - [COPD exacerbation--what should be done?].
AB  - Acute exacerbation of COPD is characterized by a worsening of the general state
      of health, breathing difficulty and greenish or yellowish sputum indicating a
      bacterial infection. A pulmonary function test and if necessary, a blood gas
      analysis are recommended for determining the severity of the exacerbation.
      Depending on severity, therapy consists of bronchial dilators, antibiotics and
      additionally if needed, steroids and oxygen as well as nonpharmacological
      measures (giving up smoking, patient education, vaccinations, etc).

PMID- 18064816
TI  - [Botulinum toxin in pain therapy].
AB  - In pain therapy we are repeatedly faced with the problem that the available
      treatment methods are inadequate. For years we have also been using botulinum
      toxin especially for myofascial pain and chronic headaches. Unfortunately, the
      assessment of its efficacy in both everyday clinical conditions and in studies is
      very variable. A final evaluation is not yet possible. Until the results of
      current studies are available, the use of botulinum toxin should be limited to
      clinical studies and to particular cases at specialized centres.

PMID- 18064817
TI  - [Long-acting bronchodilator agents are the choice in COPD. Keeping the airways
      open continuously].

PMID- 18064818
TI  - [Innovative inhalation system can improve compliance. Long-term therapy becomes
      simpler].

PMID- 18064819
TI  - A model of bacterial cell cycle duration based on DnaA dynamics and estimation of
      the population cost of bacterial plasmids.

PMID- 18064820
TI  - Juvenile hormone and 20-hydroxyecdysone regulate N-acetyltransferase activity in
      Drosophila virilis.

PMID- 18064821
TI  - A study of barrier activity of 1A2 insulator of Drosophila melanogaster.

PMID- 18064822
TI  - On the correlation between the synonymy of codon usage and taxonomy.

PMID- 18064823
TI  - The code-based physics of formation of alpha-helices and beta-hairpins in water
      soluble proteins.

PMID- 18064824
TI  - Luminous bacteria as potential producers of resorbed polyhydroxyalkanoate
      polyesters.

PMID- 18064825
TI  - A study of the structure of 1A2 insulator of Drosophila melanogaster.

PMID- 18064826
TI  - Carotenoid-photosensitized oxidation of bacteriochlorophyll dimers in light
      harvesting complexes B800-850 in Allochromatium minutissimum cells.

PMID- 18064827
TI  - Enzymological characteristic of the cholinesterase from the caudate nucleus of
      the Ladoga seal (Phoca hispida ladogensis) brain.

PMID- 18064828
TI  - S/MAR and TRE can be found co-localized within regulatory chromosome regions of
      some tissue-specifically expressed genes of Drosophila melanogaster.

PMID- 18064829
TI  - Quantum yield of charge separation and fluorescence in photosystem II of green
      plants.

PMID- 18064830
TI  - Involvement of two plastid signals in the regulation of expression of nuclear
      gene for the chloroplast protein elip.

PMID- 18064831
TI  - System for purification of complexes of the Drosophila melanogaster chromosomal
      protein SUUR.

PMID- 18064832
TI  - Molecular-genetic characteristics of the Du323 locus containing various
      microsatellite types in the parthenogenetic lizard Darevskia dahli (Lacertidae).

PMID- 18064833
TI  - Optimal coupling of subantennas as a strategy for efficient functioning of the
      light-harvesting antennas in photosynthesizing organisms: model computations.

PMID- 18064834
TI  - Determination of the melting site of the DNA duplex in the active center of
      bacterial RNA-polymerase by fluorescence quenching technique.

PMID- 18064835
TI  - Synthesis of hepatitis B virus surface antigen in tomato plants transgenic for
      the preS2-S gene.

PMID- 18064836
TI  - [Social representations: a key for public health interventions].

PMID- 18064837
TI  - [An original service for help in writing].

PMID- 18064838
TI  - [Anonymous and free screenings: population comparison between those conducted on
      site in a testing centre and those done off-site].
AB  - The free and anonymous HIV testing centre of Fernand Widal Hospital (CDAG)
      regularly organises off-site visits to distribute information and provide
      screening for people at high risk in the community. To demonstrate the benefits
      of this action, this at-risk targeted population in the community was compared
      with that which comes to the centre. The individuals screened during the
      community off-site visits in 2005 were recorded. An equivalent number of patients
      coming spontaneously to the centre for screening were used as a reference point
      for comparison. The socio-demographic characteristics, the delay in time between
      the screening and return to the CDAG for the results and the screening results of
      the number of people infected were analysed. In total, 427 persons out of 443
      were screened in 14 visits: 7,7% of persons tested off-site were infected versus
      5,4% of those screened at the centre. Those who were tested off-site were in most
      cases infected with Hepatitis C, whereas HIV was more prevalent in those who had
      come to the CDAG centre. The African population (53,6%) was more significantly
      affected. Even when their results were positive (83,3%), 34,2% of patients tested
      off-site did not come to get their results versus only 8,2% of those who had come
      to the hospital centre for testing. The off-site community visits strengthen the
      role and the capacity of the CDAG to fulfil its mission because high-risk
      individuals are much less likely to come to the centre for screening. However
      measures must be taken and procedures established to improve the process and
      opportunity for results to be returned to the individuals, as well as follow-up
      and management of those who test positive for infection.

PMID- 18064840
TI  - [Perspectives on junior high school students' well-being according to members of
      the educational community: an exploratory study].
AB  - The objective of this study was to explore descriptions and portrayals of
      students' well-being developed by members of the educational community. Fourteen
      semi-structured interviews were conducted in a secondary school in Burgundy
      (France). The results reveal that the educational staff and the school in general
      do not pay much attention to the students' physiological needs or their most
      basic fundamental needs. When educational team members discuss students' well
      being, they essentially refer to material and organizational needs, and tend to
      associate the idea of well-being with a medical concept. Study results highlight
      a significant need for training educational staff about physical and
      psychological changes of adolescent and teenaged students. A complementary study
      could help investigate these exploratory results on a larger scale for more broad
      based general conclusions.

PMID- 18064839
TI  - [Childhood fever in a zone of malaria prevalence in Benin: qualitative analysis
      of factors linked to seeking care].
AB  - In Benin, mothers usually go to health facilities when childhood malaria is
      already in its late stage (severe anaemia, convulsions, unconsciousness). This
      study was undertaken in a rural area of Benin through a community-based
      participation action-research aiming to control child malaria with a focus on
      parental participation. The aim of this research was to better understand the
      situation with regards to parents' perceptions and perspectives of childhood
      fever, care seeking behaviour and practices as well as factors that influence the
      choice of treatment among the various options. The parents were interviewed
      individually and in focus groups. Care seeking behaviour is strongly influenced
      by perceptions and personal opinions of childhood fever, which is considered as
      commonplace and not warranting care in a health centre. Severe malaria cases are
      perceived as a manifestation of the "bad eyes" and health facilities are
      consulted only as a last resort. Adequate child malaria control programmes must
      involve parents in order to take into account their perceptions of the
      implications of childhood fever.

PMID- 18064841
TI  - [Opinions, perceptions and description of cannabis amongst future health
      educators in training in France].
AB  - In France, the number of cannabis users has doubled over the last ten years. The
      groups most affected are 18-25 year old adults in higher education. This study
      involved 300 persons currently undergoing core health education training (79
      teachers, 135 nurses and 86 social workers). As health educators in training,
      they were subject to the completion of an adapted version of the EROPP survey
      (Exploring the Representations, Opinions and Perceptions of Psychotropic Drugs).
      Results were compared with those of a French survey of the general population
      undertaken in 2002. Differences between the study and the control groups, and
      between the different types of students, were analysed using the Chi-square test.
      Cannabis users were also compared with non-users. The results show an over
      consumption of cannabis in the study group compared to the general population,
      especially in men, both in terms of experimentation and current use. The
      specificities of each group are analysed and the results discussed in light of
      the study group's potential role in health education.

PMID- 18064842
TI  - [Quality of care given to seriously ill children in a provincial hospital in
      central Africa].
AB  - The aim of this study is to describe the quality of care provided to children
      hospitalized in the provincial hospital of Goma (HPG) and to identify the risk
      factors in the management of care, especially those which can contribute to a
      poor or inaccurate prognosis, and to uncover and show any inadequacies in care
      management. The data were collected with the use of a structured questionnaire
      updated by Nolan in 2001. The study allowed us to look at the initial assessment
      of incoming patients and to describe the quality of triage, emergency care,
      diagnosis, inpatient care, staff knowledge and practices, hospitals support
      services and any factors related to these that may lead to negative outcomes. The
      level of the severity of the illness and a late diagnosis were risk factors
      identified for mortality. The quality of care provided to the children during the
      day was high and good; however, night time care was insufficient. It was noted
      that nurses were found to lack adequate knowledge.

PMID- 18064843
TI  - [Doctor-patient communication and patient education, bring various notions
      together: contributions from the literature].
AB  - For 30 years, international publications have displayed agreement on the fact
      that a certain level of doctor-patient communication improves their respective
      satisfaction, the patient's quality of life, the treatment process and clinical
      results. Furthermore, patient's increased participation with decision-making
      related to their medical treatment decreases anxiety and improves health. What
      does doctor-patient communication mean and what place is made for patient
      participation? What are the similarities and the differences between approaches
      aiming at improving communication on the one hand, and approaches specifically
      related to patient education on the other? The article explores these questions
      in three parts. First, it presents the results of a literature review on
      communication within health care relationships and about consultation models from
      different disciplinary fields. This allows us to cross reference different points
      of view on this particular setting and situation for interaction. Secondly, the
      consultation models that enhance patient's participation are converged with
      intervention models promoted in patient education and health education
      activities. Finally, the skills required for adequate doctor-patient
      communication are compared with the recognized core skills and competencies in
      patient education and health education practice.

PMID- 18064844
TI  - [Interventions aimed at adolescents to stop smoking: the "Today, I don' t smoke"
      programme in high schools in the Paris metropolitan region].
AB  - Tobacco use is in itself a public health issue, but it also represents an
      identified entry point to the consumption of other toxic products. The key age
      group for initial consumption is that around the end of junior high school and
      the beginning of high school, when students' high level of autonomy is combined
      with a new set of educational circumstances and challenges. Intervening in a
      school or educational setting is not easy and often criticized. This programme
      involved around fifty secondary schools in the greater Paris metropolitan region,
      followed over several years, benefiting from substantial evaluation, including
      evaluation of results. The action combines a collective intervention in the
      classrooms coupled with the availability of a CO-testing stand to which the young
      people have open access. Several tools were created, including tools for
      evaluation. Significant preparation work and the creation and strengthening of
      solid partnerships were necessary, with a very strong investment in
      sustainability. The positive results which have been observed allow for the
      consideration of transfer methods for reproducing the activity combining two
      approaches into a repetitive and continuous process.

PMID- 18064845
TI  - [Acting on environment or individuals: comparisons in health promotion between
      Quebec and France].

PMID- 18064846
TI  - Work in progress.

PMID- 18064847
TI  - Changing the norms.

PMID- 18064848
TI  - School matters.

PMID- 18064849
TI  - A funding model for health visiting: baseline requirements--part 1.
AB  - A funding model proposed in two papers will outline the health visiting resource,
      including team skill mix, required to deliver the recommended approach of
      'progressive universalism,' taking account of health inequalities, best evidence
      and impact on outcomes that might be anticipated. The model has been discussed as
      far as possible across the professional networks of both the Community
      Practitioners' and Health Visitors' Association (CPHVA) and United Kingdom Public
      Health Association (UKPHA), and is a consensus statement agreed by all who have
      participated.

PMID- 18064850
TI  - Challenges in health visitor prescribing in a London primary care trust.
AB  - In this primary care trust there was limited health visitor prescribing. A case
      study approach sought to identify reasons for this, to lead to recommendations
      and changes to develop health visitor prescribing. The situation was examined
      using qualitative methods to consider the opportunities and challenges in health
      visitor prescribing. Semi-structured interviews with eighteen health visitors and
      managers explored their views of health visitor prescribing and its position
      within the PCT. The findings demonstrated only three health visitors prescribed;
      yet the majority were positive about prescribing, both for clients and health
      visitor development. Practitioners recognised their difficult working context and
      felt that organisational systems were not supportive of prescribing. A culture of
      prescribing was not felt to be in evidence, but was seen as a realistic
      possibility. Recommendations for change focused on the organisation and
      practitioners, with improved communication and structures supportive of
      prescribing. There was a need for practitioners to be active in learning so that
      they could share knowledge, experience and commitment to prescribing in locally
      based groups.

PMID- 18064851
TI  - A research evaluation of health support workers in a Sure Start project.
AB  - Sure Start is a government initiative aimed at reducing the effects of poverty on
      pre-school children and their families in deprived areas. Skill mix has been
      identified in recent policies as a credible way of providing high quality
      services in a cost effective manner. Health support workers, under the
      supervision of health visitors, provide support through home visiting, group work
      and clinics with research identifying that such interventions can have beneficial
      outcomes for children and their families. This research is part of a larger study
      that evaluated a Sure Start service in a borough in south Wales, using realistic
      evaluation. The aim of this aspect of the study was to ascertain the
      effectiveness and acceptability of the services provided by the health support
      workers. Qualitative methods included focus group discussions with service
      providers (10 health visitors and six health support workers) and semi-structured
      interviews with seven service users. Content analysis inductively developed
      categories and themes. The main findings show that health visitors and service
      users valued the input of the health support workers but there were important
      issues regarding training and supervision that needed to be addressed.

PMID- 18064852
TI  - Centre offers glimmer of hope.

PMID- 18064853
TI  - Use of medication in children with psychiatric disorders.
AB  - This article looks at the most common drugs that are in use in child psychiatry,
      and discusses their main indications for use and possible side effects.

PMID- 18064854
TI  - NHS pensions are changing.

PMID- 18064855
TI  - Survey shows ongoing crisis in health visiting.

PMID- 18064856
TI  - Leading edge. Interview by Carol Harris.

PMID- 18064857
TI  - [Chest pain due to a panic disorder: the significance of a multidisciplinary
      approach].
AB  - A 50-year-old man and a 76-year-old woman were presented with noncardiac chest
      pain at a medical-psychiatric unit, which is a dual medical and psychiatric
      inpatient unit in the University Hospital Maastricht, Tthe Netherlands. Since
      more than one year both patients had had complaints without a medical explanation
      for their symptoms. Somatic and psychiatric investigations were performed by a
      multidisciplinary team. Both patients were diagnosed with a panic disorder which
      has been shown to be highly treatable. Panic disorder induced noncardiac chest
      pain is a common problem that often remains unrecognized, due to the fact that
      patients primarily report somatic symptoms. The consequences are a high medical
      consumption and economic costs due to loss of working days. Moreover, anxiety may
      even increase cardiac morbidity and mortality directly. This stresses the
      importance of effective screening for psychopathology in this large group of
      patients. A multidisciplinary approach is advisable to motivate such patients for
      treatment, as they accept the presence of a psychiatrist in a combined clinic
      more readily.

PMID- 18064858
TI  - [Mesothelioma incidence around Goor, The Netherlands, and far beyond: the
      asbestos drama unfolds].
AB  - Whereas the carcinogenic properties of asbestos have been known for more than 70
      years, the mesothelioma epidemic in Europe has not yet reached its peak. After
      occupationally induced cases, environmental cases are being revealed at an ever
      increasing rate. In 2005 a total ban on the production and use of asbestos in
      Europe was announced. Worldwide, the use of asbestos has shifted towards emerging
      economies such as those occurring in Asia. Economic reasons and a strong lobby
      from the asbestos industry explain the delay in the implementation of proper
      preventive actions as well as the global shift. The WHO and the International
      Labour Office are collaborating towards the elimination of asbestos-related
      diseases worldwide. More awareness is needed in order to prevent similar
      tragedies occurring from other side effects of work.

PMID- 18064859
TI  - [Infusion of inotropic agents at home in patients with severe heart failure: an
      important role for the nurse practitioner].
AB  - Patients with severe heart failure commonly require intravenous inotropic agents
      to stabilise their haemodynamics and improve the clinical symptoms. Continuous
      intravenous inotropic agents in a home-based setting under the direction of
      specialised nurses has been introduced in patients waiting for cardiac
      transplantation and also as destination therapy. Since 1982, several case reports
      and case series have described the use of ambulatory intravenous dobutamine, but
      almost none of the available studies included a control group. Moreover, most
      trials were small and short in duration, and thus have not been able to provide
      reliable information about the effect of treatment on the risk of serious cardiac
      events. However, these data consistently demonstrate the feasibility of home
      infusion as well as an improved quality of life and reduced costs. Therefore,
      home infusion of dobutamine guided by a specialised nurse may be desirable in
      patients waiting for heart transplantation or as destination therapy in the last
      weeks of life.

PMID- 18064860
TI  - [The influence of the pharmaceutical industry on treatment guidelines].
AB  - The Dutch Health Care Inspectorate has issued a short report on the influence
      pharmaceutical companies may have on the development process of clinical
      treatment guidelines in The Netherlands. The Inspectorate concludes that
      virtually all opinion leaders are financially supported by pharmaceutical
      companies, and therefore, potential conflicts of interest are unavoidable. The
      Inspectorate recommends making these potential conflicts of interest more
      transparent by means of the full disclosure of all connections, in particular
      those related to funding, between guideline committee members and pharmaceutical
      companies. In addition, the Inspectorate suggests that formally allowing
      pharmaceutical companies the opportunity to comment on draft versions of a
      guideline may reduce other undesirable initiatives that influence guidelines.
      Additional means of regulating the influence of pharmaceutical companies should
      be considered. One such additional measure could be a qualitative and
      quantitative limit on conflicts of interest e.g. substantial personal income from
      pharmaceutical companies should preclude guideline committee membership. In
      addition, an independent review committee who would judge whether a guideline
      shows signs of interference by pharmaceutical companies may be considered.

PMID- 18064861
TI  - [The influence of the pharmaceutical industry in patient organisations].
AB  - Most patient organisations have no objection to sponsoring by the pharmaceutical
      industry. Only 5% of all organisations are against sponsoring. When patient
      organisations were asked whether or not their activities could continue without
      sponsoring, 42% answered no, 6% yes, and 52% felt that they might continue, but
      restricted. In a report of the public health inspector on the subject,
      transparency is considered to be a remedy for the entanglement between patient
      organisations and the pharmaceutical industry. However, the authors doubt that
      this is effective. The government should provide sufficient support for patient
      organisations so that they can become independent from the industry.

PMID- 18064862
TI  - [Hypertension as a source of cognitive regression, or dementia].
AB  - Cognitive deterioration and its sequelae of vascular or Alzheimer's dementia is
      rapidly increasing all over the world. This is primarily caused by the worldwide
      increase of the ageing population. Additional causes may be sought in factors
      such as genetics and a habitually unhealthy life style. The significance of high
      blood pressure in the process leading to cognitive deterioration is relatively
      unknown. However, timely detection and treatment of hypertension seems to
      contribute to the preservation of cognition. Experience has shown that this
      applies in particular to dihydropyridine calcium antagonists. Medical care tends
      to make insufficient use of the existing possibilities for treating hypertension.

PMID- 18064863
TI  - [Immunological defense to viral infections: focus on virus-specific T cells].
AB  - T cells play a central role in the control of and the protection against viral
      infections. The T cell population consists ofa diversity ofvirus-specific memory
      T cells. The characteristics of these T cells seem to depend largely on the type
      of virus for which they are specific. T cells directed against latent viruses,
      such as cytomegalovirus, are cytotoxic cells. T cells directed against viruses
      that after the initial infection are completely removed by the immune system,
      such as the influenza virus, are non-cytotoxic cells. The development of new
      immunological techniques, such as the detection of virus-specific cells with HLA
      peptide tetrameric complexes, enables the characterization of the properties of
      virus-specific T cells in the blood and organs.

PMID- 18064864
TI  - [Bronchopulmonary dysplasia in ex-prematures approaching adulthood].
AB  - Many patients born prematurely who developed bronchopulmonary dysplasia (BPD) as
      neonates are now approaching adulthood. Adults with BPD are at increased risk for
      respiratory difficulties including respiratory and lung function disorders.
      Respiratory symptoms include wheezing, cough and dyspnoea. In adult BPD patients
      lung function is impaired, notably by bronchus obstruction, hyperreactivity and
      reduced diffusion capacity; exercise capacity is also diminished. The
      pathophysiology of BPD is not identical to that of asthma and standard treatment
      for asthma is therefore not effective. Premature infants are currently treated
      with surfactant therapy that results in less intensive artificial respiration and
      oxygen being required. The classical BPD clinical picture that results from
      tissue damage and scarring is therefore becoming less common but another new BPD
      picture is emerging. This is characterised by large irregularly formed sacculi
      and alveoli with septation only just beginning and poor vascularization. Patients
      with chronic respiratory symptoms who were born prematurely should therefore
      undergo comprehensive testing, including detailed lung function tests and exhaled
      nitric oxide levels.

PMID- 18064865
TI  - [Diagnostic image (348). A man with peculiar calcifications on an abdominal X
      ray].
AB  - An X-ray of the abdomen of a diabetic dialysis patient showed typical signs of
      extra-skeletal calcification with mediasclerosis and calcification of the vasa
      deferentia.

PMID- 18064866
TI  - [Environmental exposure to asbestos in the area around Goor has been established
      as the cause of pleural mesothelioma in women].
AB  - OBJECTIVE: To determine whether a disease cluster of 22 additional cases of
      pleural mesothelioma among women could be attributed to environmental asbestos
      exposure due to asbestos fibers from waste material on roads and property yards.
      The women studied were observed in an area with substantial environmental
      exposure to asbestos during the period 1989-2002. DESIGN: Ecological study.
      METHOD: In the study period of 1989-2002, all cases of mesothelioma among women,
      based on a strict histopathologic definition, occurring in the region of Twente,
      The Netherlands (n = 59) were provided by the regional cancer register.
      Additional information was collected on the occupational histories of the cases
      and their partners and addresses of residence through medical records, general
      practitioners, and next-of-kin. Environmental asbestos exposure was assigned to
      all cases that had had a long-term stay in a house in the area around Goor with
      demonstrated local environmental asbestos pollution and where any contact with
      asbestos through occupation or in the household had been excluded. RESULTS: In
      the risk area around Goor, out ofa total of 28 cases ofwomen with pleural
      mesothelioma, asbestos in the environment was found to be the only source of
      asbestos exposure for to women. In a further 4 women, environmental asbestos
      exposure was found to be the most likely cause of pleural mesothelioma. The
      average cumulative exposure was around 0.11 fiber/ml x exposure years. The
      observed extra incidence of 22 cases was attributed to the environmental exposure
      to asbestos in 64% (14/22) of cases. CONCLUSION: The environmental pollution to
      asbestos waste materials in the area around Goor was the main cause of the
      strongly increased incidence of pleural mesothelioma among women in this area.
      Taking into account an equal risk among men, the consequences of asbestos
      exposure in the area around Goor in the next 25 years are likely to result in 2
      cases of pleural mesothelioma each year.

PMID- 18064867
TI  - [Dobutamine therapy at home under the guidance of a nurse practitioner, either as
      a bridge to cardiac transplantation or as destination therapy in severe heart
      failure].
AB  - OBJECTIVE: To evaluate the results of intravenous dobutamine therapy at home for
      ambulatory patients with severe heart failure. DESIGN: Retrospective. METHOD:
      Data were retrieved for the 40 patients that had been treated with intravenous
      dobutamine at home during the period from 1 January 1994 until mid-November 2006
      at the Thorax Centre of Groningen University Medical Centre, The Netherlands. The
      patients were guided by a nurse practitioner. RESULTS: The study group comprised
      31 men and 9 women. The 22 patients on the waiting list for a heart transplant
      had an average age of 49 years. For the other 18 patients, on average 63 years
      old, it was destination therapy. The mean administered dosage ofdobutamine was 4
      microg/kg/ min (range: 2-10). Pre-transplantation and destination therapy were
      given for an average of 3.5 and 1.5 months, respectively. A successful
      transplantation was performed in 14 (64%) of the 22 waiting-list candidates; 2
      patients were still on the waiting list and 6 died while on the waiting list.
      Intravenous access complications and ICD shocks each occurred in 6 (15%)
      patients. The quality of life was reasonable to fair in the waiting-list patients
      and moderate to reasonable in those given destination therapy. The costs for
      medication and hire of the infusion pump were Euro 450 per month. CONCLUSION:
      Dobutamine infusion therapy at home under the guidance of a nurse practitioner,
      either as a bridge to cardiac transplantation or as destination therapy in
      patients with severe heart failure, appeared safe, feasible and not expensive.

PMID- 18064868
TI  - [Urethrovaginal reflux as a cause of urinary incontinence in girls].
AB  - Examination of an 11-year-old girl with unintentional urine loss revealed that
      during micturition, urine was flowing into the vagina. Physiotherapy, aimed at
      normalization of micturition, was successful. Urinary incontinence is a common
      problem in school-age children. It can have a lot of different causes, but an
      anatomical cause is rarely found in isolated daytime incontinence. Often,
      urethrovaginal reflux is the cause of this urinary incontinence in girls. Good
      history taking and a specific bladder diary are enough to obtain the diagnosis,
      radiological investigations are not necessary. The problem is easily resolved by
      proper instruction on voiding by a qualified physiotherapist.

PMID- 18064869
TI  - [A mass in the popliteal fossa and leucocytosis caused by a paraneoplastic
      leukemoid reaction].
AB  - A 65-year-old woman was referred with a mass in the right popliteal fossa, fever
      and leucocytosis reaching 105 x 10(9)/l. Her medical history included the
      excision of a melanoma from the right ankle more than 20 years before.
      Ultrasound, CT and positron-emission tomography showed the mass in the right knee
      but no other lesions. The process was drained. Histological examination ofa
      subcutis biopsy indicated malignancy. Due to deterioration in her clinical
      condition amputation of the right leg was performed after which her leucocyte
      count normalized. The pathology specimen revealed a high-grade undifferentiated
      soft tissue tumour of unclear origin. Preoperatively assessed serum levels of
      granulocyte-stimulating factor (G-CSF), interleukin 6 and interleukin 8 were
      elevated to 241, 91 and 82 pg/ml respectively. After the amputation these levels
      returned to almost normal. This extreme leucocyte count may be explained by a
      paraneoplastic leukemoid reaction. It is hypothesized that the tumour cells
      produce G-CSF and other cytokines causing leucocytosis. Normalisation of the
      cytokine levels postoperatively supports this hypothesis.

PMID- 18064870
TI  - [Diagnostic image (338). An old woman with an abdominal swelling].

PMID- 18064871
TI  - [Reconsideration of psychomotor seizure--importance of medio-dorsal thalmic
      nucleus].
AB  - Recently, to my regret, the opportunities for psychiatrists to join in clinical
      and experimental activities to combat epilepsy are decreasing. In the period of
      1960-1980, experimental epileptology was one of the main areas in the field of
      psychiatry. Now, I have been given an opportunity to reevaluate my paper,
      entitled "Role of the Mediodorsal Thalamic Nucleus in Temporal Lobe Seizures--An
      Experimental Study", published in this journal in 1968. Therefore, I would like
      to reconsider psychomotor seizures, which are classified as complex partial
      seizures at present. The psychomotor seizures mentioned above are so-called
      amygdalo hippocampal seizures. At first, I was very much interested in the
      amygdala and hippocampus, because these seizures are quite similar to psychomotor
      seizures which are clinically observed in epileptics. I observed a lot of
      important phenomena. A amygdaloid and hippocampal seizures are quite different
      from each other, both regarding their behavior and EEG findings which are
      observed during the attacks. Hippocampal seizures consisted of staring in the
      arrest reaction. On the contrary, amygdaloid seizures showed typical automatisms,
      such as facial and behavioral automatisms. From these results, it was considered
      that the clinically observed psychomotor seizures began in the hippocampus and
      immediately induced the self-sustained amygdaloid seizures. In my experiments, I
      often observed that self-sustained amygdaloid seizures were easily induced by
      hippocampal seizures. Moreover, I noted the fact that stimulation of the
      mediodorsal thalamic nucleus elicited both amygdaloid and hippocampal seizures.
      By means of stimulation and surgical interruption methods among the dorsomedial
      thalamic nucleus, amygdala, and hippocampus, I found that the dorsomedial
      thalamic nucleus plays the main role in amygdalo-hippocampal seizures. According
      to my experiments, the thalamic nucleus controls the limbic seizures. So, I
      concluded that the therapeutic approach to the mediodorsal thalamic nucleus is
      clinically very important. I think that, through these experimental studies, I
      could profoundly understand epilepsy itself and the development of seizure
      discharge in the brain, and put this understanding to good use in my clinical
      activities. It is my belief that experiments which are performed by clinicians
      field useful results which can be utilized clinically.

PMID- 18064872
TI  - [Treatment of depression from the point of view of suicide prevention].
AB  - In recent years, the annual number of suicide victims is over 30,000 in Japan.
      Most of the these suicides are considered to be caused by depressive disorders.
      Therefore, intervention in the early stage of depression must be performed to
      prevent suicide. Firstly, new antidepressant drugs such as SSRIs and SNRIs are
      very useful to treat depressive disorders without severe adverse effects, which
      might lead to a good rate of adherance to the drugs. However, the use of newer
      antidepressant drugs might be accompanied with some problems such as activation
      syndrome, serotonin syndrome, withdrawal syndrome, and suicidal-like behaviors.
      Secondly, it is important to predict whether the response to antidepressant drugs
      will shorten the treatment period. The polymorphisms of 5-HTTLPR and plasma MHPG
      levels might predict the response to SSRIs and SNRIs. Thirdly, we should work to
      achieve complete remission including social adjustment and also adjustment in the
      work place instead of just partial remission. SASS is one of the useful rating
      scales for assessing social adaptation. In addition, the continuation of
      maintenance treatment for a sufficient duration is necessary to prevent relapse.
      Taken together, early intervention with precise pharmacotherapy (ECT or rTMS in
      refractory cases) and psychotherapy is important to prevent suicide.

PMID- 18064873
TI  - [Psychiatric background of social withdrawal in adolescence].
AB  - In recent years, Japan's mental health welfare service personnel are encountering
      a growing number of adolescents in whom social withdrawal persists for extended
      periods. The provision of treatment and support for these individuals has become
      a challenge that needs to be addressed on a nationwide scale. This study was
      conducted to identify the guidelines for treating and assisting adolescents who
      manifest social withdrawal behaviors, and to clarify the psychiatrist's role. Of
      the consultation requests sent to the Yamanashi Prefectural Mental Health Welfare
      Center, cases of adolescents manifesting social withdrawal behaviors were
      classified into the following three groups and studied: (1) the Consultation
      Group (the subject himself/herself came to the center and made use of the
      consultation and assistance services), (2) the Non-Consultation Group (only the
      subject's family came to the center for consultation, and the staff were unable
      to meet him/her), and (3) the Consultation-after-Family Support Group (those
      subjects in the Consultation Group whom the staff could finally meet after one
      year or more of consultations with the family). As a result, we learned that
      adolescent cases of social withdrawal could be diagnosed and classified, in
      principle, according to the current diagnostic criteria (DSM-IV), and that, from
      here on, we aim to psychiatrically elucidate the pathology by focusing on
      international diagnostic criteria. We also showed that, compared with the
      Consultation Group, the Non-Consultation Group had a greater number of subjects
      with no employment history. The subjects within this group, moreover, tended to
      exhibit even more serious problems, and there was a possibility that the family
      structure and circumstances influenced whether or not the subjects visited the
      center for consultation. We also determined some of the issues related to
      assistance and support provided to individuals who fail to come to the center for
      consultation. Furthermore, we showed the possibility that psychiatry and
      psychiatrists play a wide variety of roles in dealing with the issue of social
      withdrawal in adolescence. These include: (a) cases in which a psychiatrist is
      called upon to provide diagnosis and treatment, (b) cases in which non-medical
      consultation service institutes play a central role in providing assistance in
      daily living and matters relating to employment, and a psychiatrist is called
      upon to provide adequate diagnosis and guidance, and (c) cases in which a
      psychiatrist collaborates and cooperates with private sector support groups.

PMID- 18064874
TI  - [Value of diffusion-weighted MR imaging in the detection of middle ear
      cholesteatoma].
AB  - OBJECTIVE: This study, was conducted to determine the clinical value of diffusion
      weighted MR imaging (DWI) in detecting the presence of cholesteatoma. SUBJECT AND
      METHODS: Fifty-six patients (21 female and 35 male patients; mean age, 43 years)
      who underwent middle ear surgery were referred to the radiology department for a
      preoperative DWI study. RESULTS: DWI depicted 41 out of 48 cholesteatomas
      involving the middle ear cavity (sensitivity, 85.4%). Seven patients with middle
      ear cholesteatoma who showed negative DWI findings (false-negative cases) had
      limited keratin accumulation due to simple atelectasis or meticulous evacuation
      of keratin debris before the MRI study. No falsepositive cases were found in this
      study (specificity, 100%). The positive predictive value and negative predictive
      value were 100% and 53.3%, respectively. The minimum size of middle ear
      cholesteatoma detected by the current MRI system was 5mm. CONCLUSION: Diffusion
      weighted MR imaging was useful for the detection of middle ear cholesteatoma.

PMID- 18064875
TI  - [Characteristics of migrating cells in effusion of the middle ear in patients
      with "eosinophilic otitis media"].
AB  - Otitis media with effusion (OME) is known to be a disease that frequently
      afflicts children. Recently, numerous reports of intractable OME associated with
      bronchial asthma have been reported, generally referred to as "eosinophilic
      otitis media". To comprehend the cause and pathogenesis of this disease, we
      conducted an electron-microscope analysis of the effusion. The subjects were 5
      male and 1 female patients, 4 had aspirin-induced asthma and 2 had adult-onset
      asthma. The number of collapsed and intact eosinophils and other inflammatory
      cells in the middle ear effusion were counted, and their characteristics were
      reviewed. Most eosinophils in the middle ear effusion were collapsed, and a high
      percentage of eosinophils in the nasal discharge were also collapsed. The
      inflammatory cells were phagocytosed by macrophages at a high frequency in cases
      of otitis media with effusion, but only a low rate of phagocytosis was observed
      in cases with eosinophilic otitis media. It is known that necrotic cells are
      phagocytosed with difficulty, while apoptotic cells are phagocytosed easily by
      macrophages. Therefore, collapsed eosinophils persist for a long time in middle
      ear effusion and the released granule proteins from the eosinophils cause the
      tissue failure. Threfore, we believe that treatment directed at causing apoptosis
      of eosinophils can prevent exacerbation of the intractable inflammation in this
      condition.

PMID- 18064876
TI  - [Dynamic vestibular compensation in vestibular peripheral diseases].
AB  - Vestibular compensation, or neuronal plasticity in the central vestibular system,
      is quite an important process in patients with acute unilateral peripheral
      vestibular disease, allowing them to lead a comfortable daily life when medical
      treatments fail to cure the peripheral vestibular function. Is the residual
      unilateral vestibular input from damaged vestibular endo-organs a positive or
      negative factor for the development of dynamic vestibular compensation in the
      central nervous system? To elucidate the true mechanism of vestibular
      compensation, we examined the ENG findings and dizziness handicap inventory
      questionnaire in patients with vestibular neuronitis (VN), sudden deafness with
      vertigo (SDV), Meniere's disease (MD) and acoustic tumor (AT) during remission of
      the vertigo attacks. We obtained neuro-otological findings from caloric tests and
      head shaking after nystagmus using ENG and information on motion-evoked dizziness
      in daily life using the questionnaire. There were no significant differences in
      the sex, age or canal paresis % (CP%) among the four groups. The results of the
      present study showed that dynamic vestibular compensation processes developed
      progressively in the order of patients with SDV, VN, MD and AT (Kruskal-Wallis :
      p < 0.05). This finding suggests that processes of dynamic vestibular
      compensation could be accelerated in patients with fixed vestibular lesions
      caused by SDV and VN more than in those with fluctuating vestibular functions
      caused by MD and AT. In patients with fixed vestibular lesions caused by SDV and
      VN, patients with lower CP% showed dynamic vestibular compensation (i.e.
      disappearance of head shaking after nystagmus (chi-square: p < 0.05) and motion
      evoked dizziness (Mann-Whitney: p < 0.0005)) more rapidly than those with higher
      CP%. In patients with fluctuating vestibular functions caused by MD and AT,
      patients with lower CP% did not always develop dynamic vestibular compensation
      more smoothly than those with higher CP%.

PMID- 18064877
TI  - [Personal identification using information from cranio-facial region].
AB  - Much of Forensic Odontology is concerned with personal identification, through
      examination of cranio-facial region. This paper describes several studies in
      which we worked with materials derived from cranio-facial region. The following
      topics are addressed : (1) Human saliva contains proteins specific to salivary
      glands, proteins which are highly polymorphic compared with those found in other
      body fluids. In particular, six genes for proline-rich proteins coded many
      proteins found in human saliva, and we found several of them. At least five kinds
      of cystatin are secreted in saliva. We constructed recombinant polymorphic
      proteins, cystatin SAl and SA2. Using these proteins, we compared effects of
      amino acid mutation on protease inhibitor activity, and demonstrated a novel
      function for type-2 cystatin cytokine-inducing activity. (2) Among autosomal STR
      loci, we identified the D12S67 locus as highly polymorphic, with a heterozygosity
      of 95%, by investigating differences in nucleotide repeat units. Highly
      polymorphic autosomal STR loci offer an effective forensic tool under certain
      conditions, in addition to multiplex PCR, and therefore merit further study in
      forensic practice. (3) Although digitalization is prevalent in photography,
      analog images are preferable in certain circumstances as they offer better
      resolution. (4) Usually, information on mtDNA polymorphisms from HV1 and HV2 in
      the control region is used in forensic practice. However, information from the
      coding region considerably increases the discrimination power of mtDNA
      polymorphisms. It is important to increase the volume of coding region
      information available with regard to mtDNA polymorphisms for future forensic
      practice. (5) Y-STR polymorphisms are closely associated with binary haplogroups,
      and it is possible to estimate a binary haplogroup from an STR haplotype. (6)
      Mitochondrial DNA and Y-chromosomal polymorphisms can be used to determine
      geographic origin in individuals from East Asia, something that was considered
      difficult in the past. (7) A Dental Scan was constructed for the preparation of
      dental records. It offers a superior method to the taking of pictures as is done
      in standard forensic odontology.

PMID- 18064878
TI  - [Verification of the method for estimating age-at-death using maxillary suture
      obliteration in Japanese].
AB  - The method for estimating age-at-death of human skeletal remains based on the
      morphological changes of maxillary sutures is widely accepted in Japan. This
      method is based on the work of Kamijo (1949), which describes the age-related
      alternations in the morphology of maxillary sutures in Japanese population.
      However, from the modern anthropological viewpoint, Kamijo's report has some
      serious flaws in the definition of the morphology of the sutures as well as in
      the quality and quantity of the samples. Despite these problems, no verification
      has been conducted for the validity of estimating age-at-death based on his data.
      Recently, Mann et al. (1991) published a new method for estimating skeletal age
      based on the progressive obliteration of maxillary sutures. However, there has
      been no report that verified the effectiveness of their method in Japanese. In
      the present study, we re-examined the age-related alternations in the
      morphologies of maxillary sutures in Japanese and assessed the effectiveness of
      the method of Mann et al. (1991) by using 375 (274 males and 101 females)
      Japanese skeletons of known sex and age. In all maxillary sutures, the
      morphological transitions from "no obliteration" to "partial obliteration" with
      age could be confirmed. However the transition from "partial obliteration" to
      "complete obliteration" with age could be seen only in the incisive suture and
      the posterior median palatine suture. Moreover the percentage of each morphology
      of suture to a total within each decade shows almost no change over fifth decade.
      By using the method of Mann et al., we could correctly estimate the age-at-death
      of only 36.9% for males and 25.7% for females of the Japanese samples, however,
      we seldom overestimated the age-at-death of these samples compared with their
      actual age. This finding suggests that this method is applicable to estimate the
      minimum age-at-death in Japanese population.

PMID- 18064879
TI  - [Pulmonary asbestosis: an autopsy case].
AB  - The deceased was a 75-year-old male, found dead in his home. He had a history of
      occupational asbestos exposure for 13 years. At autopsy, there was diffuse
      fibrosis of the lung, with diffuse pleural thickening. Large amounts of asbestos
      bodies were detected in the lung tissue. The findings of transmission electron
      microscopy with energy-dispersive X-ray microanalysis (TEM-EDX) also showed
      asbestos fibers deposited in the lung tissue. From the macroscopic and
      histological findings of the lung, the number of asbestos bodies in the lung
      tissue and the TEM-EDX findings, we concluded that the cause of his death was
      chronic respiratory failure due to asbestosis. We recognize the importance of a
      detailed occupational history, which provides useful information for determining
      the cause of death.

PMID- 18064880
TI  - [Floral transition around summer solstice of rice, a short-day plant: What
      occurred in rice domestication?].

PMID- 18064881
TI  - [Domestication of rice and barley viewed by plant type].

PMID- 18064882
TI  - [Molecular phylogenetics of cultivated plants, with special reference to maize
      and common wheat].

PMID- 18064883
TI  - [Maize domestication and breeding based on genomic variation].

PMID- 18064884
TI  - [Wheat domestication and bread wheat speciation: variation produced by
      intraspecific differentiation and allopolyploidization].

PMID- 18064885
TI  - [Domestication of barley: two-row and six-row problems].

PMID- 18064886
TI  - [Morning glory mutants induced by transposable elements in the Edo era].

PMID- 18064887
TI  - [Molecular basis of ryanodine receptor-mediated Ca2+ release].

PMID- 18064888
TI  - [Transcription factor AhR is a ligand-dependcnt E3 ubiquitin ligase].

PMID- 18064889
TI  - [Odorant-binding proteins and evolution of host-plant preference in insects].

PMID- 18064890
TI  - [The phenomenon of spatial synchronization of the brain potentials in a broad
      frequency band 1-250 Hz].
AB  - A review. The article dedicated to the centenary of academician Mikhail
      Nikolaevich Livanov briefly outlines the history of development of his original
      concept of the functional significance of the brain potential's spatial
      synchronization phenomenon as a possible way of studying systemic organization of
      the brain electrical activity. The new parameter of "space" introduced into
      neurophysiology by M. N. Livanov made it possible to research the earlier unknown
      aspect of the brain activity. Livanov's ideas have been developed in many studies
      of the late decades of the XX century. In the review, much attention is given to
      specific functional significance of this phenomenon in a broad frequency band 1
      250 Hz, especially, during instrumental learning. Energy (power spectra) and
      coherent-phase characteristics of cortical potentials in traditional (1-30 Hz),
      gamma-(30-80 Hz) and high-frequency (80-250 Hz) bands are compared. The problem
      of linear and nonlinear processes in the organization of the brain potentials is
      mentioned.

PMID- 18064891
TI  - [Activation and inhibitory types of brain neuronal sinchronisation: genesis and
      functional significance].
AB  - The generalization of studies of the systemic work of cortical neurons during the
      information processing initiated in Livanov's laboratory allows us to make the
      following conclusions in terms of the modem state of the problem. In different
      brain structures, there is a considerable degree of correlation between neuronal
      activities and slow potential oscillations. In the state of rest or deep
      extinction, the synchronization of brain neurons increases by the inhibitory
      type. In the active state of the brain, the degree of neuronal synchronization
      increases by the activation type. Both processes are determined by the
      involvement of the whole brain inhibitory or activation systems, respectively. A
      relative augmentation of inhibitory processes results in a restriction of
      information transmission in the cortex and prevents its fixation in memory of the
      system. A decrease in inhibition facilitates the excitation thransmission in the
      interconnected brain structures. Synchronous convergence of ordered polse flows
      ensures the information fixation during learning.

PMID- 18064892
TI  - [The role of cytokines in the seizure activity development in the brain].
AB  - In this review, the role of pro-inflammatory cytokines, interleukin-1 (IL-1) and
      tumor necrosis factor-alpha (TNF-alpha), and anti-inflammatory cytokine, IL-10,
      in the seizure activity development is analyzed. In recent years, there has been
      increasing evidence that the transformation of normal pattern of neuronal
      activity to paroxysmal one is associated with the increased production of these
      cytokines in the brain. However, the present results indicate that expressions of
      IL-1, TNF-alpha and IL-10 in the brain are associated with cell injury rather
      than with seizures per se. These findings suggest that, in response to seizures,
      these cytokines cause both neuroprotective or neurodegenerative effects and, as a
      consequence of these effects, the further facilitation or depression of seizure
      activity.

PMID- 18064893
TI  - [Motivation effect on power changes in the brain biopotentials in the figurative
      and verbal creativity tasks].
AB  - Effect of extrinsic motivation stimulating the most original problem solving
      during verbal and figurative divergent thinking was studied by EEG mapping. The
      righthanded university students (27 males and 26 females) participated in the
      experiments. An instruction "to create the most original solution" as compared to
      condition with an instruction "to create any solution" induced an increase in the
      baseline power of the alpha 1 and alpha 2 rhythms most pronounced in the
      posterior cortex. Task-related desynchronization of the alpha rhythms was higher
      but the beta-2 synchronization was lower after the former than after the latter
      instruction. Differences in the asymmetry of the alpha 1 and alpha 2 rhythms in
      the parietal and temporal regions of hemispheres suggested the right hemisphere
      dominance in intrinsic alertness and evoked activation related to divergent
      thinking. The findings were common and gender-independent in both figurative and
      verbal tasks suggesting a generalized influence of extrinsic motivation on
      creative activity.

PMID- 18064894
TI  - [Late negativity in visual event-related potentials in humans to changes in
      topology of simple nonverbal stimuli].
AB  - Late negativity arising in ERP in response to a semantic mismatch of consistently
      presented stimuli is usually considered to be related with verbal or symbolic
      representation of stimulus during perception. It is shown in this work that the
      late negativity typical of the semantic mismatch develops even in the context of
      non-symbolic and nonverbal, for example, four-point stimulus compositions which
      differ only in typology or angular size. Attention distraction from trial stimuli
      completely eliminates the effect of the late negativity. It is suggested that the
      brain finds semantic and formal (physical) descriptions for any stimulus
      composition. This phenomenon is reflected in the N400 amplitude depending on the
      attention volume to the stimuli per se.

PMID- 18064895
TI  - [Two semantic brain systems for rapid and slow differentiation of the abstract
      and concrete words].
AB  - In the previous studies, semantic processing was repeatedly found to be reflected
      in the late (300-800 ms) components of event-related potentials (ERP). However, a
      human may catch the meaning of the words much earlier. In this work we
      investigated brain mechanisms of semantic analysis of abstract and concrete
      written words in four experimental conditions: (1) simple reading (a subjects had
      to read words to him/herself); (2) simple classification (a subjects had to
      classify presented words into abstract and concrete categories); (3) cued and (4)
      uncued selective classification conditions (a subject had to classify only the
      words typed in a particular color). In the simple reading condition, early (40
      100 ms) differences between the ERPs to concrete and abstract words were found
      mostly in the right frontal areas. During simple classification, the early
      differences between the ERPs were observed in more dorsal areas. Differences in
      the late ERP components (450-700 ms) in the left frontal area were characteristic
      of all cases of explicitly classified words. The findings suggest the existence
      of two semantic systems: a rapid implicit system which involves the right frontal
      cortex and can be suppressed by task demands, and a slow explicit system of word
      classification involving, predominantly, the left frontal area.

PMID- 18064896
TI  - [Estimation of color and brightness differences by neurons in the rabbit superior
      colliculus].
AB  - Changes in activity of 83 neurons in the rabbit colliculus superior evoked by the
      replacement of eight color and eight achromatic stimuli in pairs were analyzed.
      It was found out that neurons displayed the early and late phasic responses
      (within 50-90 and 120-300 ms respectively, after the replacement) and long-term
      tonic response component, which depended on stimuli intensity. Analysis of phasic
      component revealed three neuronal groups. The first group (n=25, 30%) selected on
      the basis of the earliest component, was specialized to differentiate stimuli
      only by intensities. The perceptual spaces of these neurons reconstructed on the
      basis of spike discharge in the earliest response were two-dimensional. The
      second group of neurons (n=16, 19%) selected on the basis of the late phasic
      component demonstrated four-dimensional structure of perceptual space. Neurons of
      the third group (n=4, 5%) possessed a two-dimensional structure of perceptual
      space reconstructed by the analysis of the early component, whereas analysis of
      the late response revealed a four-dimensional structure. We suggest that
      information about differences between stimuli in color and intensity coming from
      cortical neurons is necessary for the reconstruction of four-dimensional space.
      The structure of perceptual spaces reconstructed on the basis of phasic responses
      of neurons in the colliculus superior was similar to the spaces of neurons in the
      primary visual cortex and lateral geniculate nucleus. The structure of perceptual
      space reconstructed on the basis of neuronal spikes was also similar to the space
      calculated from the N85 component of the visual evoked potential recorded under
      similar conditions. This finding confirms the general principle of vector coding
      in the visual system.

PMID- 18064897
TI  - [Blood testosterone in rats: correlation with individual anxiety and its
      derangement after the "death threat"].
AB  - After preliminary testing on a multiparameter scale, test and experimental groups
      of Wistar male rats were formed on the principle of identical distribution of
      individuals with different anxiety levels. A negative Spearman correlation
      between the testosterone blood concentration and the level of anxiety was
      observed in intact rats: the minimum hormonal concentrations (lower than 5
      nmol/l) were found in rats with high anxiety, whereas the maximum concentrations
      (up to 16 nmol/l) corresponded to the higher anxiety level (prevalence of passive
      defense reactions during testing). After a sort-term exposure to life-threatening
      situation (viewing of a boa's attacking and devouring two victim rats from the
      test group), the correlation was deranged because of appearance of a scatter in
      testosterone blood concentration (from 3 to 21 nmol/l) in rats with low anxiety.
      Neurotization with inescapable pain stimulation also deranged the initial anxiety
      testosterone correlation, but, as distinct from the exposure to life-threatening
      situation, eliminated individual differences in testosterone concentration at its
      low level. The results suggest the existence of multiple ways of adaptation to
      life-threatening situations in a rat population.

PMID- 18064898
TI  - [Asymmetry in the dopamine content in the nucleus accumbens and the motor
      preference in rats].
AB  - A number of published studies reported a correlation between the paw preference
      in mice and asymmetry of tissue concentrations of dopamine (DA) and DA
      metabolites measured in the nucleus accumbens (NAcb) the DA concentration being
      higher in the nucleus ipsylateral to a preferred paw. This study aimed to
      investigate whether such asymmetry existed in rats. The paw preference was
      defined by reaching into a small horizontal tube for a food pellet. Tissue
      concentration of DA was measured by high-performance liquid chromatography with
      electrochemical detection. It was shown that the DA concentration in the left
      NAcb was significantly higher in "left-handed" rats than in "right-handed"
      animals. Within the group of "right-handers", the DA concentration was
      significantly higher in the right NAcb than in the left NAcb. The results confirm
      in part the experimental data obtained in mice and support the hypothesis that
      the paw preference is paralleled by elevated tissue DA in the ipsylateral NAcb of
      rodents.

PMID- 18064899
TI  - [The reproductive correlates of social hierarchy in laboratory male mice].
AB  - In laboratory male mice the effects of social hierarchy on hormonal and
      spermatogenic testicular function, accessory organs and testicular weights,
      sexual behaviour have been investigated using an experimental model of social
      hierarchy, which is characterised by a minimal size (two male mice) and 5 days
      period of social interactions. The social rank of the partners was detected by
      asymmetry in aggressive behaviour. Using the experimental condition, when the
      both partners have no preferences for exclusive use of area we demonstrated that
      there were no rank differences in the number of mounts and testicular
      testosterone content. Nevertheless a rank asymmetry in the male sniffing
      behaviour towards a receptive female, weights of the testes, seminal vesicles,
      epididymes and the number of epididymal sperm was kept up in a stable social
      group. Social dominance was found to affect negatively on testicular testosterone
      increase in response to introduction of a receptive female and sexual
      attractiveness of male to a receptive female in both dominant and subordinate
      males. The results obtained demonstrate the impact of social hierarchy on
      reproduction in laboratory male mice, particular in respect of spermatogenesis
      and the testicular testosterone in response to a receptive female.

PMID- 18064900
TI  - [Behavior of mice from different strains: modifications produced by noopept].
AB  - Genotype-dependent behavioral effects were demonstrated in BALB/c, C57BL/6J
      [Russian character: see text] DBA/2J mice after injections of nootropic drug
      Noopept. In an elevated plus maze, drug administration induced an increase in the
      number of enterings into bright arms in BALB/c mice, whereas the opposite effect
      was observed in C57BL/6J. After the Noopept administration, animals from all the
      three strains increased the number of active avoidance reactions in stress
      inducing slip-funnel test. A significant intensification of exploration behavior
      was observed in a closed plus-maze in BALB/c and C57BL/6J. The Noopept affected
      weakly or had no effect on the behavior of DBA/2J mice.

PMID- 18064901
TI  - [Alterations in the oscillatory activity of neurons in the medial septal area in
      animals with the chronic temporal lobe epilepsy model].
AB  - Comparative investigation of activity of medial septal neurons, which was
      performed by extracellular recordings in the brain slices of health guinea pigs
      and in such ones of animals with the model of chronic temporal lobe epilepsy,
      revealed the distinctions between them, concerning a neuronal frequency and
      pattern of discharges. In the epileptic brain, twofold increase of general level
      of activity was observed comparative to control one, owing to augmentation of
      frequency of discharges in non-regular and regular non-bursting neurons. Sharp
      increase (three times as much) of number of cells with rhythmic burst discharges
      and changing of parameters of burst activity were discovered, the letter both in
      the neurons with endogenous (pacemaker) pattern and in the cells secondary
      involved in the rhythmic activity. Possible mechanisms of these alterations are
      discussed. The present data advance the understanding of the processes of a
      pathological synchronization and may promote creation of new approaches to
      treatment this disease.

PMID- 18064902
TI  - [Basic steps of EEG topogram analysis development by the Livanov's school].
AB  - The basic steps of development of the topogram analysis technique are outlined
      with its prerequisites. A topogram is defined as a set of momentary EEG values
      simultaneously recorded from the whole scalp surface with multiple electrodes.
      Experimental evidence points to existence of two main types of the spatiotemporal
      organization of the cortical potentials varying in time in the whole range of the
      EEG frequencies. Animal and human experimental data are described which reveal
      either dominance of one of these types or their complex interaction.

PMID- 18064903
TI  - [M. N. Livanov's studies on the consequences of exposure to ionizing radiation].

PMID- 18064904
TI  - [Solving the riddle of the brain rhythms].

PMID- 18064905
TI  - [Expression of the enzymes of dopamine synthesis in non-dopaminergic neurons:
      functional significance and regulation].
AB  - Dopamine(DA), the most widely distributed in the nervous system and functionally
      important chemical signal, is synthesized in DA-ergic neurons from L-tyrosine by
      means of two enzymes, tyrosine hydroxylase (TH) and aromatic L-amino acid
      decarboxylase (AADC). Apart from the enzymes, specific DA transporter is an
      attribute of DA-ergic neurons. In the mid eighties of the last century, in
      addition to DA-ergic neurons, those expressing only one enzyme, TH or AADC, have
      been discovered. These "monoenzymatic" neurons occurred to be more numerous and
      more widely distributed in the brain compared to DA-ergic neurons that manifests
      their wide involvement to the brain functioning. It has been demonstrated that
      the monoenzymatic neurons expressing complementary enzymes of DA synthesis
      produce this neurotransmitter in cooperation. In this case, L-tyrosine is
      transformed to L-DOPA in TH containing neurons that is followed by L-DOPA release
      and uptake from the intercellular space to AADC containing neurons for DA
      synthesis. Moreover, the L-DOPA uptake to DA-ergic or serotoninergic neurons
      results either in the increase or the onset of DA synthesis in addition to
      serotonin, respectively. The expression of the enzymes of DA synthesis in non
      dopaminergic neurons is one of the adaptive reactions serving to compensate the
      functional insufficiency of DA-ergic neurons. For instance, hyperprolactinemia
      and the deficiency of DA, prolactin-inhibiting hormone, which is developed under
      degeneration of DA-ergic neurons of the arcuate nucleus, are compensated with
      time due to the increase of the number of monoenzymatic neurons and cooperative
      synthesis of DA in the nucleus. It is supposed that the same compensatory
      cooperative synthesis of DA is turned on under the degeneration of DA-ergic
      neurons of the nigrostriatal system that is manifested by the appearance of non
      dopaminergic neurons expressing enzymes of DA synthesis in the deafferentated
      striatum. The expression of the enzymes of DA synthesis in non-dopaminergic
      neurons is under the control by intercellular signals, catecholamines,
      neurotrophic (growth) factors and, perhaps, hormones. Thus, non-dopaminergic
      monoenzymatic neurons expressing enzymes of DA synthesis produce this
      neurotransmitter in cooperation that is a compensatory reaction under functional
      insufficiency of DA-ergic neurons, in neurodegenerative diseases,
      hyperprolactinemia and Parkinson's disease, in particular.

PMID- 18064906
TI  - [A role of dopamine-dependent activity reorganizations in the cortico-basal
      ganglia-thalamocortical loops in visual attention (hypothetical mechanism)].
AB  - A mechanism of attention is proposed according to which its influence on visual
      processing is switched on by release of dopamine into the striatum. A dopamine
      release during involuntary attention is promoted by visual activation of
      striatonigral cells via the thalamus and subsequent disinhibition through the
      basal ganglia of the superior colliculus. A dopamine release during voluntary
      attention is promoted by activation of prefrontal cortex. The strengthening of
      responses of neocortical neurons to attended stimulus, and suppression of
      responses to other stimuli is the result of opposite modulatory action of
      dopamine on the efficacy of strong and weak corticostriatal inputs. This leads to
      changes in the output basal ganglia signals ("attentional filter") that exert
      disinhibitory and inhibitory influence (via the thalamus) on neocortical cells
      that initially were strongly and weakly activated by a stimulus, respectively.
      From proposed mechanism follows, that attention modulates only those components
      of responses of cortical neurons which latency exceeds the latency of reactions
      of dopaminergic cells (80-100 ms).

PMID- 18064907
TI  - [Nitric oxide (NO) and NO cycle in myocardium: molecular, biochemical and
      physiological aspects].
AB  - The article continues the series of our publications on the problem of nitric
      oxide (NO) and its cyclic conversion in mammals. This review is held to analysis
      of nitric oxide role in regulation of cardiovascular system and in alocation of
      NO-synthases in myocardium. Molecular, biochemical and cytophysiological aspects
      that linked, with spatial localization of NO-synthases and mechanisms of NO
      content regulation in myocardium are considered. The results of author's
      investigations along the cyclic convertion of NO and literature data about
      compartmentalization of NO-synthases in myocardium are included in this paper.
      The contradictory and dissimilar facts about regulatory and toxic role of nitric
      oxide in cardiovascular system are represented.

PMID- 18064908
TI  - [Speach breasing optimization with biofeedback on respiratory arrythmia of heart
      rate].
AB  - Dynamics of physiological and psychological characteristics of healthy volunteers
      (adolescents and adults), speech professionals (logopedics), and stutter patients
      (adolescents and adults) in process of adoptive self-regulation with biofeedback
      on objective physiologic indicator - changes of respiratory arrhythmia of hart
      rate were investigated. High level of efficacy and practicability of the method
      application was revealed to study, diagnostics, optimization and correction of
      breathing, speech and behavior.

PMID- 18064909
TI  - [Physical and neurological state of the newborn after perinatal asphyxia].
AB  - Asphyxia neonatorum is the most prevalent birth trauma. Usually it leads to the
      birth of weak and nonvigorous child. Perinatal asphyxia is the reason of not only
      postasphyxic hypoxic-ischemic encephalopathy, but also multiple organ
      dysfunctions. Neurological sequelae and consequences of multisystem dysfunction
      affect on newborn status in first life months and later on by the muscle tone
      disturbances, physical and mental retardations. In this paper it is presented
      modern conceptions about asphyxia origin, risk factors, neurological and systemic
      complications for child nervous system and organism.

PMID- 18064910
TI  - [The experimental models of Parkinson's disease in animals].
AB  - The current review describes the modem Parkinson's disease models in animals,
      their advantages, limitations and disadvantages. It was noted that the most
      widespread up-to-date models based on etiology of the Parkinson's disease.
      Although toxins mostly produce the Parkinson's disease, a study of involved genes
      allows investigating not only inherited but also sporadic (not inherited) forms
      of disease since the same genes are involved in both cases. Mutations of genes
      lead to formation of "mutant" toxic proteins, which produce a death of the
      specialized neurons of the nigrostriatal dopaminergic system and the development
      of Parkinson's disease. A significant place in the review takes adescription of
      characteristics of the toxic models produced by 6-OHDA, MPTP and rotenone, their
      similarities and differences in pathogenetic mechanisms of the Parkinson's
      disease development. On the basis of the considered experimental models of
      Parkinson's disease a conclusion has been done that none of these models may in
      full and adequate scale imitate the entire clinical, pathophysiological,
      morphological, biochemical and other aspects of the Parkinson's disease
      development.

PMID- 18064911
TI  - [Stress concept in the centennial of Hans Selye].
AB  - Stress concept substantially evolved since its creation by Hans Selye in 1936.
      New definitions of the stress were suggested. The knowledge of the stress
      mechanisms and mediators was widened. The changes in genes activities were
      included in the list of participants of the stress response along with the
      hormones, neurotransmitters and tissue factors. "Nonspecificity" of the stress
      response mechanisms was defined more exactly, especially concerning their
      neuronal parts. The stress theory was enriched by the idea of "allostasis".
      Stress concept and the discussions on it stimulated investigation of molecular
      genetic mechanisms of the organisms' defensive reactions, and this concept still
      retain its significance for modem biomedical sciences.

PMID- 18064912
TI  - Space suit bioenergetics: cost of transport during walking and running.
AB  - Space suits significantly affect the metabolic cost of human movement during
      extravehicular activity, a key component of future human missions to the Moon and
      Mars. We hypothesized that space suit legs act as springs during running, thereby
      lowering cost of transport relative to space-suited walking. METHODS: We
      transformed data from suited and unsuited energetics studies into a common format
      and developed a regression equation for specific resistance, S, (energy per
      weight per distance) based on the Froude number (a nondimensional parameter
      associated with gait transitions), surface slope, gravity, and space suit
      pressure. Acceptance criteria for regression factors included significance and a
      reduction in residual variance. We divided suited data into two groups, running
      and walking or slow running, and performed a group means hypothesis test and
      categorical regression of metabolic rate per unit weight and S, measures of time-
      and distance-associated metabolic efficiency, respectively. RESULTS: The
      regression on S achieved an adjusted R2 of 0.83; all factors were significant (P
      < 0.0005). No additional evaluated factors met the acceptance criteria. The
      categorical regression, but not the hypothesis test, suggested that the running
      group had reduced efficiency per unit time; both tests suggested that the running
      group had increased efficiency per unit distance. DISCUSSION: The regression
      model largely explained variations in S across studies. Several findings suggest
      that gas-pressure space suit legs function as springs during running, including
      the finding of higher efficiency per unit distance during running, despite the
      presumed increased work against space suit joint torques at higher velocities.

PMID- 18064913
TI  - Endothelial role in the thoracic aorta response to hindlimb unloading in rats.
AB  - BACKGROUND: Hindlimb unloading (HLU) is used to simulate microgravity in rats and
      has been shown to decrease contractile response in the abdominal aorta. The
      thoracic aorta has not been studied as thoroughly. METHODS: Wistar and Sprague
      Dawley rats were subjected to HLU for 20 d and the thoracic aortas were isolated
      and sectioned into 3-mm rings for the measurement of isometric force development.
      Concentration response curves (CRCs) to phenylephrine (PHE) were obtained in
      endothelium-intact and -denuded rings from both strains of rats. Acetylcholine,
      methylfurmethide (MFM), and sodium nitroprusside (SNP) CRCs were obtained in the
      Wistar rats. RESULTS: HLU had no effect on the contractions of endothelium-intact
      Wistar aortas to PHE, but decreased the maximal PHE-induced contraction (2.82 +/-
      0.16 g Control vs. 2.18 +/- 0.11 g HLU) in intact Sprague-Dawley aortas. After
      endothelium removal, HLU increased the contractions of Wistar, but not Sprague
      Dawley, aortas to PHE (1.91 +/- 0.12 g Control vs. 2.95 +/- 0.13 g HLU). HLU had
      no effect on the relaxation to acetylcholine, but increased the sensitivity to
      the relaxing effects of MFM (LOG EC50 -6.96 +/- 0.12 Control vs.-7.31 +/- 0.17
      HLU) and SNP (LOG EC50 -7.90 +/- 0.15 Control vs.-8.35 +/- 0.10 HLU) in the
      Wistar rats. SUMMARY: It is concluded that HLU increased smooth muscle
      contracting and endothelium-dependent relaxing capacities equally in the Wistar
      aortas, and had no effect on smooth muscle, but increased endothelium-dependent
      relaxation, in the Sprague-Dawley aortas.

PMID- 18064914
TI  - Oxidative stress levels in rats following exposure to oxygen at 3 atm for 0-120
      min.
AB  - BACKGROUND: Hyperbaric oxygen (HBO) is known to cause oxidative stress in several
      organs and tissues. We previously defined the pressure-related oxidative effects
      of HBO in several tissues of rats. This study was performed to elucidate the
      relationship of HBO exposure time to its oxidative effects. METHODS: A total of
      49 rats were randomly divided into 5 groups. Study groups were subjected to 3 atm
      HBO for 30, 60, 90, and 120 min except the control group. Their blood and lungs
      were removed immediately after exposure and used for analysis. Thiobarbituric
      acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione
      peroxidase (GSH-Px) levels were determined to reflect oxidant and antioxidant
      status. RESULTS: TBARS levels were found to increase in a time-dependent manner
      in both erythrocytes [median (min-max); from 0.65 (0.39-0.84) with 30 min HBO
      exposure up to 1.26 (1.00-1.44) nmol x g(-1) hemoglobin after 120 min] and lung
      tissue [from 2140 (1550-2510) up to 5465 (5090-5950) nmol x g(-1) protein].
      Similarly, SOD activity also presented a dose-dependent course from 0.06 (0.05
      0.10) to 0.18 (0.14-0.26) U x g(-1) hemoglobin in erythrocytes and from 16,660
      (3479-25,994) to 52,522.5 (41,362-65,799) U x g(-1) protein in lung tissue. In
      contrast, GSH-Px activity reflected an irregular trend; its levels were mostly
      found to be increased, but they were decreased at one stage (in the erythrocytes
      of 30-min exposed rats). CONCLUSIONS: The results of this study exhibited a clear
      relationship of HBO-induced oxidative action to exposure time. This action was
      most pronounced from 90 to 120 min of exposure.

PMID- 18064915
TI  - Antioxidant pretreatment and reduced arterial endothelial dysfunction after
      diving.
AB  - INTRODUCTION: We have recently shown that a single air dive leads to acute
      arterial vasodilation and impairment of endothelium-dependent vasodilatation in
      humans. Additionally we have found that predive antioxidants at the upper
      recommended daily allowance partially prevented some of the negative effects of
      the dive. In this study we prospectively evaluated the effect of long-term
      antioxidants at a lower RDA dose on arterial endothelial function. METHODS: Eight
      professional male divers performed an open sea air dive to 30 msw. Brachial
      artery flow-mediated dilation (FMD) was assessed before and after diving.
      RESULTS: The first dive, without antioxidants, caused significant brachial
      arterial diameter increase from 3.85 +/- 0.55 to 4.04 +/- 0.5 mm and a
      significant reduction of FMD from 7.6 +/- 2.7 to 2.8 +/- 2.1%. The second dive,
      with antioxidants, showed unchanged arterial diameter and significant reduction
      of FMD from 8.11 +/- 2.4 to 6.8 +/- 1.4%. The FMD reduction was significantly
      less with antioxidants. Vascular smooth muscle function, assessed by
      nitroglycerine (endothelium-independent dilation), was unaffected by diving.
      DISCUSSION: This study shows that long-term antioxidant treatment at a lower RDA
      dose ending 3-4 h before a dive reduces the endothelial dysfunction in divers.
      Since the scuba dive was of a similar depth and duration to those practiced by
      numerous recreational divers, this study raises the possibility of routine
      predive supplementation with antioxidants.

PMID- 18064916
TI  - Oxygen administration, cerebral blood flow velocity, and dynamic cerebral
      autoregulation.
AB  - INTRODUCTION: Hyperoxia is reported to decrease steady-state cerebral blood flow
      (CBF). In addition, dynamic cerebral autoregulation would be altered. Hyperoxia
      may improve dynamic cerebral autoregulation, contrary to hypoxia. However, no
      previous studies have examined changes in steady-state CBF velocity (CBFV) and
      alterations of dynamic cerebral autoregulation during acute exposure to
      hyperoxia. We, therefore, evaluated dynamic cerebral autoregulation
      simultaneously with steady-state CBFV during stepwise hyperoxia under oxygen
      administration. METHODS: There were eight healthy volunteers who were examined
      under normoxic (21% O2) and hyperoxic conditions in stepwise fashion to 40%, 70%,
      and 100% O2. Mean blood pressure (MBP) in the radial artery was measured via
      tonometry, and CBFV in the middle cerebral artery was measured by transcranial
      Doppler ultrasonography. Dynamic cerebral autoregulation was assessed by spectral
      and transfer function analysis of beat-to-beat changes in MBP and CBFV. RESULTS:
      End-tidal CO2 decreased significantly at 70% and 100% O2. Steady-state CBFV
      decreased significantly at F1O2 > or = 40%, while MBP was unchanged. Associated
      with these changes, cerebral vascular resistance index increased at 70% and 100%
      O2. Transfer function gain and coherence remained unchanged at all levels of
      F1O2. DISCUSSION: These results suggest that hyperoxemia and hypocapnia reduce
      steady-state CBFV and increase cerebral vascular resistance during oxygen
      administration. This reduction in steady-state CBFV occurs even during mild
      hyperoxia < or = 40% O2 and becomes obvious at 70% O2 with hypocapnia. However,
      dynamic cerebral autoregulation may remain unchanged during hyperoxia, even with
      apparent changes in steady-state CBFV.

PMID- 18064917
TI  - Tactile cueing effects on performance in simulated aerial combat with high
      acceleration.
AB  - INTRODUCTION: Recent evidence indicates that vibrotactile displays can
      potentially reduce the risk of sensory and cognitive overload. Before these
      displays can be introduced in super agile aircraft, it must be ascertained that
      vibratory stimuli can be sensed and interpreted by pilots subjected to high G
      loads. METHODS: Each of 9 pilots intercepted 32 targets in the Swedish Dynamic
      Flight Simulator. Targets were indicated on simulated standard Gripen visual
      displays. In addition, in half of the trials target direction was also displayed
      on a 60-element tactile torso display. Performance measures and subjective
      ratings were recorded. RESULTS: Each pilot pulled G peaks above +8 Gz. With
      tactile cueing present, mean reaction time was reduced from 1458 ms (SE = 54) to
      1245 ms (SE = 88). Mean total chase time for targets that popped up behind the
      pilot's aircraft was reduced from 13 s (SE = 0.45) to 12 s (SE = 0.41). Pilots
      rated the tactile display favorably over the visual displays at target pop-up on
      the easiness of detecting a threat presence and on the clarity of initial
      position of the threats. DISCUSSION: This study is the first to show that tactile
      display information is perceivable and useful in hypergravity (up to +9 Gz). The
      results show that the tactile display can capture attention at threat pop-up and
      improve threat awareness for threats in the back, even in the presence of high
      end visual displays. It is expected that the added value of tactile displays may
      further increase after formal training and in situations of unexpected target pop
      up.

PMID- 18064918
TI  - Parachute landing fall characteristics at three realistic vertical descent
      velocities.
AB  - INTRODUCTION: Although parachute landing injuries are thought to be due in part
      to a lack of exposure of trainees to realistic descent velocities during
      parachute landing fall (PLF) training, no research has systematically
      investigated whether PLF technique is affected by different vertical descent
      conditions, with standardized and realistic conditions of horizontal drift. This
      study was designed to determine the effects of variations in vertical descent
      velocity on PLF technique. METHODS: Kinematic, ground reaction force, and
      electromyographic data were collected and analyzed for 20 paratroopers while they
      performed parachute landings, using a custom-designed monorail apparatus, with a
      constant horizontal drift velocity (2.3 m x s(-1)) and at three realistic
      vertical descent velocities: slow (2.1 m x s(-1)), medium (3.3 m x s(-1)), and
      fast (4.6 m x s(-1)). RESULTS: Most biomechanical variables characterizing PLF
      technique were significantly affected by descent velocity. For example, at the
      fast velocity, the subjects impacted the ground with 123 degrees of plantar
      flexion and generated ground reaction forces averaging 13.7 times body weight,
      compared to 106 degrees and 6.1 body weight, respectively, at the slow velocity.
      Furthermore, the subjects activated their antigravity extensor muscles earlier
      during the fast velocity condition to eccentrically control the impact
      absorption. DISCUSSION: As vertical descent rates increased, the paratroopers
      displayed a significantly different strategy when performing the PLF. It is
      therefore recommended that PLF training programs include ground training
      activities with realistic vertical descent velocities to better prepare trainees
      to withstand the impact forces associated with initial aerial descents onto the
      Drop Zone and, ultimately, minimize the potential for injury.

PMID- 18064919
TI  - Stressful military training: endocrine reactivity, performance, and psychological
      impact.
AB  - INTRODUCTION: We examined the responsiveness of both cortisol and
      dehydroepiandrosterone sulfate (DHEAS) to the stress of survival training in
      military men and evaluated relationships to performance, peritraumatic
      dissociation, and the subsequent impact of stressful events. METHODS: Baseline
      salivary cortisol samples were self-collected by 19 men at 0900 and 1930 in a
      free-living (FL) environment. DHEAS samples were also collected in a subset of
      this sample (N = 12). Samples were subsequently taken at similar time points
      during a stressful captivity (SC) phase of training. Repeated-measures analyses
      of variance with follow-up paired t-tests examined differences across time and
      conditions. RESULTS: Significant increases were observed at both time points
      (0900 and 1930) from FL to SC in both cortisol (0900: 9.2 +/- 3.4 nmol x L(-1)
      vs. 18.4 +/- 10.5 nmol x L(-1); 1930: 3.5 +/- 3.0 nmol x L(-1) vs. 27.7 +/- 10.9
      nmol x L(-1)) and DHEAS (0900: 1.7 +/- 1.3 ng x ml(-1) vs.6.7 +/- 3.5 ngx ml(-1);
      1930: 1.5 0.84 ng x ml(-1) vs. 4.5 +/- 3.0 ng x ml(-1)). Also, overall
      performance during a high-intensity captivity-related challenge was inversely
      related to the DHEAS-cortisol ratio; conversely, overall performance during a low
      intensity captivity-related challenge was positively related to DHEAS at the 0900
      time point during SC. Dissociation was unrelated to endocrine indices measured
      during SC, while total impact of events was inversely related to percent change
      in DHEAS from FL to SC. CONCLUSIONS: Cortisol and DHEAS increase in response to
      allostatic load, and may relate to human performance during SC as well as PTSD
      symptoms.

PMID- 18064920
TI  - Dysbaric osteonecrosis in experienced dive masters and instructors.
AB  - INTRODUCTION: Dysbaric osteonecrosis (DON) is a type of aseptic bone necrosis of
      long bones such as the humerus, femur, and tibia. It is observed in workers who
      perform in high-pressure environments. METHODS: There were 58 volunteer divers
      included in this study who had performed at least 500 dives, were working as a
      dive master or instructor, had never performed industrial and commercial dives,
      and did not have a diagnosis of osteonecrosis. Radiological evaluation was
      performed according to the guidelines suggested by The British Research Council
      Decompression Sickness Panel. A total of eight X-rays were taken per patient.
      When suspicious lesions were detected, MRI of the region was performed. RESULTS:
      Of the 58 divers, 2 were eliminated because of inadequate X-ray studies. A total
      of 18 DON lesions were detected in 14 of 56 (25%) divers. Age was the only
      variable independently associated with the development of DON (P < 0.05).
      DISCUSSION: The DON prevalence of 25% in this study is high considering the dive
      instructors had thorough diving training and strictly practiced the decompression
      rules. We believe this high prevalence is a result of frequent and sometimes deep
      dives for many years. Our findings raise the question of whether these divers can
      be seen as "sports divers" or should be seen as "occupational divers." If the
      latter description is approved, dive masters and instructors should be kept under
      periodic screening for DON lesions just like professional commercial divers to
      help reduce the morbidity associated with this disease.

PMID- 18064921
TI  - Accident rates for novice glider pilots vs. pilots with experience.
AB  - INTRODUCTION: It is a popular notion in gliding that newly soloed pilots have a
      low accident rate. The intention of this study was to review the support for such
      a hypothesis from literature and to explore it using UK accident totals and
      measures of flying exposure. METHOD: Log sheets from UK gliding clubs were used
      to estimate flying exposure for inexperienced glider pilots. This was used along
      with accident data and annual flight statistics for the period 2004-2006 in order
      to estimate accident rates that could be compared between the pilot groups.
      RESULTS: The UK accident rate for glider pilots from 2004-2006 was 1 accident in
      every 3534 launches and 1590 flying hours. The lowest estimated rate for pilots
      with up to 1 h of experience was 1 accident every 976 launches and 149 h flown.
      For pilots with up to 10 h of experience the figures were 1 accident in 1274
      launches and 503 h. DISCUSSION: From 2004-2006 UK glider pilots with 10 h or less
      experience in command had twice the number of accidents per launch and three
      times as many accidents per hour flown than average for UK glider pilots. Pilots
      with only 1 h of experience or less were involved in at least 10 times the number
      of accidents per hour flown than the UK average and had more than 3.5 times the
      number of accidents per launch.

PMID- 18064922
TI  - Functional hearing in noise: insert earphones vs. supra-aural headphones.
AB  - INTRODUCTION: Aviators and aircrew members work in hostile listening environments
      on a routine basis and rely on their hearing for crew coordination, a critical
      component of rotary-wing aviation. New technology may assist in this endeavor,
      but will require aviators to have the ability to not only hear in noise, but also
      to localize warning and other signals. The Hearing in Noise Test (HINT) assesses
      functional hearing in noise, but has only been normalized using sound field
      speakers or supra-aural headphones. METHODS: There were 60 normal hearing
      students (30 men and 30 women) from Utah State University who were equally
      partitioned into 3 groups. Each group was administered the HINT in three test
      conditions with one of three transducers: 1) THD-39 supra-aural; 2) ER-3A foam
      inserts; or 3) the communications earplug. RESULTS: Analysis of the data revealed
      there was no gender difference and no significant differences between scores
      obtained using the transducers under test in any of the test conditions.
      CONCLUSION: Insert-type earphones should be considered for administration of the
      HINT.

PMID- 18064923
TI  - International Space Station medical standards and certification for space flight
      participants.
AB  - INTRODUCTION: The medical community of the International Space Station (ISS) has
      developed joint medical standards and evaluation requirements for Space Flight
      Participants ("space tourists") which are used by the ISS medical certification
      board to determine medical eligibility of individuals other than professional
      astronauts (cosmonauts) for short-duration space flight to the ISS. These
      individuals are generally fare-paying passengers without operational
      responsibilities. MATERIAL AND CONTEXT: By means of this publication, the medical
      standards and evaluation requirements for the ISS Space Flight Participants are
      offered to the aerospace medicine and commercial spaceflight communities for
      reference purposes. It is emphasized that the criteria applied to the ISS
      spaceflight participant candidates are substantially less stringent than those
      for professional astronauts and/or crewmembers of visiting and long-duration
      missions to the ISS. CONCLUSIONS: These medical standards are released by the
      government space agencies to facilitate the development of robust medical
      screening and medical risk assessment approaches in the context of the evolving
      commercial human spaceflight industry.

PMID- 18064924
TI  - Emergency medical kit for commercial airlines: an update.
AB  - In 1998, the Air Transport Medicine (ATM) Committee of the Aerospace Medical
      Association (AsMA) made its first recommendations concerning medical kits for
      commercial airlines. These were updated in 2002 and the ATM has continued to
      monitor medical kit usage, as well as pharmaceutical developments, and a further
      revision is now needed. This has taken into account ongoing work of the
      International Civil Aviation Organization and recommendations of the
      International Air Transport Association in the field of passenger and crew
      health. Based on the above, the Committee proposes the following update to its
      2002 recommendations.

PMID- 18064925
TI  - This month in aerospace medicine history--December 2007.

PMID- 18064926
TI  - High frequency EEG as source of alertness/drowsiness index and cognitive function
      capacity.

PMID- 18064927
TI  - Human spaceflight health systems for the Constellation Project.

PMID- 18064928
TI  - [Limping in toddlers due to disorders of the spine and spinal cord].
AB  - Limping is a frequent symptom during childhood and can be caused by a variety
      ofdiseases, the most common causes being trauma and infections of the bones or
      joints. The authors describe three cases of limping in toddlers caused by
      infrequent spinal diseases. The toddlers presented with limping without a
      preceding trauma. In the first patient, an 18-month-old girl, the limping was
      caused by spondylodiscitis. She recovered completely after antibiotics. The
      second patient, a 13-month-old boy, presented with limping caused by
      neuroblastoma with extensive bone metastasis. Despite chemotherapy and partial
      resection of the neuroblastoma, the boy did not survive. In the last patient, a
      19-month-old girl, the limping was caused by an intraspinal intramedullary
      astrocytoma. She recovered after partial resection of the tumour. In young
      children presenting with limping, diagnoses involving the spine should also be
      considered because early intervention can influence the prognosis favourably.

PMID- 18064929
TI  - [A flow chart for the laboratory diagnosis of anaemia as requested by general
      practice].
AB  - Anaemia is a common problem in primary care. It can be a symptom of an underlying
      disease such as a malignancy, and should therefore not be ignored. The diagnosis
      of anaemia is laboratory-based and is defined as a haemoglobin concentration
      below the lower reference value. The reference values are currently under debate;
      some authors argue that the WHO lower reference values are incorrect and should
      be replaced by higher values. Algorithms for requesting laboratory tests can be
      applied as a guide to the classification and diagnosis ofanaemia. The Dutch
      College of General Practitioners has issued such a flow chart which is based on
      Wintrobe's classification and in which the red cell volume is a central value
      i.e. the 'mean corpuscular volume' (MCV). An alternative flow chart has been
      proposed which starts with the determination of the ferritin concentration.
      However, neither of these algorithms is always practical. They often do not lead
      to a diagnosis, and combined diagnoses may not be accounted for. In general
      practice, the initial diagnosis of anaemia could be based on a reliable
      haemoglobin measurement which would establish if anaemia is or is not present.
      Consequently, a simple laboratory diagnosis algorithm could be applied to
      frequently occurring causes of anaemia, such as iron deficiency. Should the cause
      be a rarer one, then a specialist should be consulted.

PMID- 18064930
TI  - [Mediprudence based on previous cases of occupational disability].
AB  - The assessment of claims on performance restrictions as an expression of illness
      is a complex business. As well as the illness, personality factors and their
      interaction with a person's environment play an important part in the process.
      The assessment requires normative considerations. In 2005, the Health Council of
      the Netherlands advised the various medical specialists to adjust their
      guidelines in order to improve the coherence between the assessment, treatment
      and the supervision of patients. For this purpose, the so-called 3B guidelines
      had to be developed. Ahead of this and not without a certain amount of political
      pressure, the Council already drafted ten protocols related to insurance
      medicine. These protocols concern disorders that often lead to long-term
      occupational disability. Due to the limitations involved with diagnosis
      interpretation, the protocols however can only act as a rough guide. The Council
      therefore advised additional comments on relevant cases to be published.
      Mediprudence concerns general aspects and dilemmas of the assessment of claims.
      Such mediprudence has a public character and should primarily be developed by the
      professional group in collaboration with other (non-medical) disciplines and
      patient organizations. The initiative of the Health Council of the Netherlands
      may facilitate the integration of treatment of patients and assessment of claims.
      The centralized structure does not, however, guarantee the development of
      professional support. As the representative ofvarious interested parties, the
      Council avoids formulating starting points for the assessment of claims. It is
      possible that these will be addressed during the development of the mediprudence
      but this will put a very great strain on the capacities of the professional
      group.

PMID- 18064931
TI  - [The child with a tracheostomy, past and present: different indications,
      different children, different care].
AB  - --Until a few decades ago, acute infectious airway obstruction was the primary
      indication for tracheotomy in children. Its incidence has decreased considerably
      due to vaccination programmes and antibiotic treatment. --Today, the primary
      reasons for performing tracheotomy in a child are chronic airway obstruction
      (laryngeal injury after intubation, craniofacial malformation, lymphangioma) and
      prolonged artificial ventilation. --Consequently, the percentage of children who
      may be decannulated after a short period has decreased. --Tracheotomised children
      now require longer and more intensive care than before. --Hospital discharge is
      possible if parents and care providers are provided thorough training and
      counselling; this process requires specific medical, nursing and psychosocial
      support. --The increasing proportion of tracheotomised children cared for at home
      necessitates greater involvement from family practitioners.

PMID- 18064932
TI  - [Hirsutism].
AB  - --Hirsutism, defined as excessive growth of terminal hair in a male-type pattern,
      is prevalent in women and is most often a feature of androgen excess, associated
      with polycystic ovary syndrome (PCOS). Idiopathic hirsutism is the second most
      common cause. In a small minority of cases, hirsutism is the result of a serious
      adrenal or ovarian disorder. --The primary aim of diagnostic procedures is to
      establish or exclude underlying pathology. In the case ofhirsutism, i.e. a
      modified Ferriman and Gallwey score > 6, analysis of circulating androgen levels
      and other relevant endocrine parameters is indicated. --Adrenal or ovarian
      pathologies require primary therapy. --Hirsutism in women with PCOS, or without
      measurable changes in plasma androgen levels, can be treated with drugs either
      inhibiting ovarian or adrenal androgen production, blocking androgen receptors or
      inhibiting 5alpha-reductase in the hair follicle. --Spironolactone or cyproterone
      acetate combined with an oral contraceptive is the safest and most effective
      therapeutic approach. --Weight loss is an important part of the treatment of
      obese, hirsute women with PCOS.

PMID- 18064933
TI  - [Guideline 'Chronic Achilles tendinopathy, in particular tendinosis, in
      sportsmen/sportswomen'].
AB  - --Chronic Achilles tendinopathy in sports often leads to various therapeutic
      strategies, medical shopping and frequently to inability to perform at the
      desired level. --Although it is clear that this chronic tendinopathy is not an
      inflammatory disease of the tendon, the cause of the degeneration of the tendon
      fibres is not understood. --The main therapeutic measure--based on scientific
      evidence--is eccentric calf-muscle training for at least 3 months. --Recent
      therapies such as sclerotherapy ofneovascularizations in and around the Achilles
      tendon appear to be promising, but more studies are required. --About 20% of the
      patients tend to be refractive to conservative measures. --In selected cases
      surgery can be undertaken, with percutaneous longitudinal tenotomy proving
      effective in 75-80% of the cases.

PMID- 18064934
TI  - [Diagnostic image (346). A child with prominent cranial fissures].
AB  - A 2-week-old boy was presented with prominent cranial fissures. He was diagnosed
      with malleability post partum.

PMID- 18064935
TI  - [Prospective comparison of the flow chart for laboratory investigations for
      anaemia from the Dutch College of General Practitioners' guideline 'Anaemia' with
      a self-developed, substantive and logistical alternative flow chart].
AB  - OBJECTIVE: To compare the flow diagram for the diagnosis of anaemia from the
      guideline 'Anaemia' from the Dutch College of General Practitioners (NHG) with a
      substantive and logistical alternative protocol. DESIGN: Prospective. METHOD: For
      evaluation of anaemia, 124 patients from primary care reported to the
      laboratories of the St. Elisabeth Hospital in Tilburg (n = 94) and the Scheper
      Hospital in Emmen (n = 30), the Netherlands. Two flow charts were used: the NHG's
      flow chart and a self-developed chart in which not mean corpuscular volume, but
      ferritin concentration occupies the central position. All the laboratory tests
      mentioned in both flow charts were carried out in every patient with, for
      practical reasons, the exception of Hgb electrophoresis and bone marrow
      investigations. General practitioners were approached and patient dossiers were
      consulted to obtain further clinical data. RESULTS: According to the NHG
      protocol, on the grounds of the laboratory investigations, 64 (52%) of patients
      could not be put in a specific category. The majority were patients with
      normocytary anaemia who did not fulfil the criteria for iron deficiency anaemia
      or the anaemia of chronic disease. According to the alternative chart, in 36
      (29%) patients no diagnosis was made. These were patients in whom no abnormal
      laboratory findings were observed, other than low haemoglobin values. The
      majority of the patients had normocytary anaemia, in some cases this was
      interpreted as the anaemia of chronic disease, but more often the anaemia could
      not be assigned to a particular category. A large number ofpatients had a raised
      creatinine value. This value did not appear in the NHG protocol. In 15% of
      patients, more than one cause for anaemia was found. The NHG protocol did not
      enable these multiple diagnoses to be made. Accordingly, the NHG protocol was
      difficult to implement in the laboratory. CONCLUSION: Using the NHG flow diagram
      a large percentage of patients could not be assigned to a particular category.
      Using the alternative flow diagram, which procedure is easier to carry out in the
      laboratory, it was possible to make multiple diagnoses.

PMID- 18064936
TI  - [Anorectal injury after a fall from a jet ski].
AB  - A 28-year-old female sustained an anorectal rupture after a fall from a jet ski.
      The rupture was sutured and a double-loop colostomy was created. Three months
      later, following a test of functional continence, the colostomy was removed. The
      patient recovered without complications and with preservation of faecal
      continence. During a fall from a jet ski at high speeds, the water behaves as a
      solid object that penetrates the body. The choice oftreatment depends on the
      anatomical location and extent of the injury, on the comorbidity, and on a
      possible delay in the presentation of the symptoms. Wearing ofwetsuits is
      proposed as a possible preventive measure.

PMID- 18064937
TI  - [Four patients with incidentalomas of the thyroid discovered on 18-fluoro
      deoxyglucose positron-emission tomography (FDG-PET)].
AB  - In 4 patients, an incidentaloma of the thyroid was found on 18-fluoro
      deoxyglucose positron-emission tomography (FDG-PET). In the first patient, a 73
      year-old man, a medullary thyroid carcinoma was discovered during the staging
      procedure ofa laryngeal carcinoma. In the second patient, an 81-year-old woman, a
      follicular thyroid carcinoma was found as a result of a FDG-PET evaluation of an
      adenocarcinoma of the lung. In the third patient, a 64-year-old woman, a
      papillary thyroid carcinoma was found during dissemination investigation after
      curative removal of an adrenocortical carcinoma. The last patient, a 78-year-old
      man, was found to have a thyroid incidentaloma on FDG-PET scan during staging ofa
      recurrence of a gastrointestinal stromal tumour. Thyroid incidentalomas are
      present on 1.2-2.3% of FDG-PET scans. Further diagnostic work-up of these lesions
      by fine needle aspiration is warranted since up to 50% are malignant. However,
      whether these malignant thyroid lesions are relevant is not always clear.
      Treatment depends on the primary disease for which the FDG-PET scan was initially
      made. This requires good evaluation and discussion with the patient.

PMID- 18064938
TI  - [Full clinical placements for medical students can start as early as the third
      year of medical training].
AB  - The undergraduate medical curriculum in Utrecht provides students with early
      clinical experience in their third year by two full clinical placements in
      general medical areas. With this, an optimum context for the integration of
      biomedical knowledge is achieved. The doctor in training gains experience in an
      authentic setting as early as possible in the medical education programme with
      modern opinions on professionalism that fit in with current societal
      requirements.

PMID- 18064939
TI  - [Clinical placements cannot start in the third year of medical training].
AB  - A solid knowledge base is essential in order for clinical placements that include
      some responsibilities to be meaningful. As it takes at least 3 years to discuss
      all principal organ systems, clinical placements should not commence after only
      two years. In addition, the limited numbers of patients and clinical teachers may
      be better reserved for full senior clinical placements.

PMID- 18064940
TI  - [Risk factors for structural chromosomal abnormality in > or = 2 miscarriages, as
      an instrument for selective karyotyping].

PMID- 18064941
TI  - [Risk factors for structural chromosomal abnormality in > or = 2 miscarriages, as
      an instrument for selective karyotyping].

PMID- 18064942
TI  - [Ancillary diagnostic imaging is useful if there is atypical evidence of
      appendicitis].

PMID- 18064943
TI  - [The consequences of postponing pregnancy].

PMID- 18064944
TI  - [Turner syndrome in adulthood].

PMID- 18064945
TI  - [Guideline on polyneuropathy].

PMID- 18064946
TI  - Relationships of Indoor, Outdoor, and Personal Air (RIOPA): part II. Analyses of
      concentrations of particulate matter species.
AB  - During the study Relationships of Indoor, Outdoor, and Personal Air (RIOPA*), 48
      hour integrated indoor, outdoor, and personal air samples were collected between
      summer 1999 and spring 2001 in three different areas of the United States:
      Elizabeth NJ, Houston TX, and Los Angeles County CA. Air samples suitable for
      analyzing particulate matter 2.5 microm or smaller in aerodynamic diameter
      (PM2.5) were collected in 219 homes (twice in 169 homes). Indoor and outdoor air
      samples suitable for gas-phase and particle-phase organic analyses were collected
      in 152 homes (twice in 132 homes). Samples or subsets of samples were analyzed
      for PM2.5 mass, organic functional groups, elements, organic carbon (OC),
      elemental carbon (EC), gas-phase and particle-phase polycyclic aromatic
      hydrocarbons (PAHs), and chlordanes. Air exchange rate (AER), temperature, and
      relative humidity were measured for each residence; questionnaire data and time
      activity information were collected from the participants. Median indoor,
      outdoor, and personal PM2.5 mass concentrations were 14.4, 15.5, and 31.4
      microg/m3, respectively. Personal PM2.5 concentrations were significantly higher
      and more variable than indoor and outdoor concentrations. Several approaches were
      applied to quantify indoor PM2.5 of ambient (outdoor) and nonambient (indoor)
      origin, some using PM2.5 mass concentrations and others using PM2.5 species
      concentrations. PM of outdoor origin was estimated in three ways using
      increasingly accurate assumptions. Comparing estimates from the three approaches
      enabled us to quantify several types of errors that may be introduced when
      central-site PM concentrations are used as surrogate estimates for PM exposure.
      Estimates made using individual measurements produced broader distributions and
      higher means than those made using a single infiltration factor for all homes and
      days. The best estimate (produced by the robust regression approach) of the mean
      contribution of outdoor PM2.5 to the indoor mass concentration was 73% and to
      personal exposure was 26%. Possible implications of exposure error for
      epidemiologic assessments of PM are discussed below. Organic particulate matter
      was the major constituent of PM2.5 generated indoors. After correcting for
      artifacts, it constituted 48%, 55%, and 61% of PM2.5 mass inside study homes in
      Los Angeles, Elizabeth, and Houston, respectively. At least 40% but probably
      closer to 75% of this organic matter, on average, was emitted or formed indoors.
      Functional group analysis provided some insights into the composition and
      properties of the indoor-generated organic PM2.5. Chlordane, a very minor but
      mutagenic semivolatile organic mixture previously used as a termiticide, was
      found to be mostly of indoor origin. High emission rates were most frequently
      found in homes built from 1945 to 1959. Analysis of the change in gas-particle
      partitioning during transport of outdoor PAHs to indoor environments illustrated
      that chemical thermodynamics can alter the concentration and composition of
      outdoor PM as it is transported indoors. (This has been previously noted for
      nitrate [Lunden et al 2003].) In epidemiologic studies that rely on central-site
      monitoring data, such transformations may result in measurement error, and this
      possibility warrants further investigation.

PMID- 18064947
TI  - [Malignant glaucoma].
AB  - Malign glaucoma is an important challenge for the ophthalmologist by the
      incomplete knowledge of the exact etiopathological mechanisms and by the fact
      that represent the most difficult type of secondary glaucoma to treat, that has a
      reserved prognostic.

PMID- 18064948
TI  - Ocular migraine and antiphospholipid antibodies--where we stand?
AB  - There is no doubt that ocular migraine also known as retinal migraine or
      ophthalmic migraine should not to be confused with ophthalmoplegic migraine. The
      hallmark of ocular migraine is the unilateral visual loss or "monocular transient
      loss of vision" associated or followed by the headache. Better safe than sorry,
      therefore an ophthalmologic examination during the migraine attack is the most
      diagnostic method. age with typical history for ocular migraine. Importantly
      supportive data sustain that different neuro-ophthalmologic manifestations as
      amaurosis fugax, retinal vascular thrombosis and optic neuropathy, may be
      considered as the ocular hallmarks of the Hughes's syndrome. Clues for the
      evaluating of antiphospholipid antibodies include recurrent thrombosis especially
      in young people, recurrent fetal loss, and thrombocytopenia. There are no studies
      that focus exclusively on the prophylaxis of ocular migraine. Ocular features due
      to antiphospholipid antibodies - induced thrombosis or Hughes's syndrome should
      be treated with anticoagulant therapy.

PMID- 18064949
TI  - Ocular manifestations of antiphospholipid (Hughes)' syndrome--minor features?
AB  - The ocular manifestations are described in autoimmune disease, being most common
      associated with systemic lupus erythematosus, scleroderma, rheumatoid arthritis,
      insulin-dependent diabetes mellitus, and dermatomyositis. Nonetheless, the
      antiphospholipid syndrome is a relatively newly recognized autoimmune disorder.
      Ocular conditions in which to consider antiphospholipid syndrome include
      amaurosis fugax, transient ischemic attack, retinal haemorrhages and cotton wool
      spots, central retinal vein and artery occlusion, anterior ischemic optic
      neuropathy, ophthalmic and cilioretinal artery occlusions. Ocular features due to
      antiphospholipid antibodies - induced thrombosis should be treated with
      anticoagulant drugs. In opposition, for the treatment of ocular features due to
      immunological mechanisms such as vasculitis, immunosuppressants seem to be more
      suitable. The aim of this article is to underline the mainly ocular features of
      Hughes' syndrome and for the most part attention should be paid to the patients
      with central retinal vascular occlusion with no cause but most likely caused by
      lupus anticoagulant.

PMID- 18064950
TI  - [Effects of optical radiation in ocular structures].
AB  - The eye and the skin are organs that are particularly vulnerable to external
      aggression, such as electromagnetic radiation- meaning ultraviolet radiation,
      visible radiation (especially blue light) and infrared radiation. The three
      mechanisms involved are: the photo-thermic mechanism, the photochemical mechanism
      and the photomechanical mechanism. The effects of such exposures can be either
      temporary or permanent, if inadequate protection occurs. Today, there are enough
      data so that special protection measures can be taken concerning the potential
      damage of optical radiation. Among those, we mention artificial implants or sun
      glasses containing UV filters or surgical gestures that can be taken to protect
      the eye against the surgical light. Ultimately, the effects of optical radiation
      upon the eye are related to being well informed about the risks of uncontrolled
      exposure and the protection measures against it.

PMID- 18064951
TI  - [Glaucoma, hydrocephaly and quadrantanopsias].
AB  - The authors present the case of a male patient who was diagnosed with juvenile
      glaucoma after an ophthalmologic examination. The patient had a previous
      diagnosis: hydrocephaly.

PMID- 18064952
TI  - [Sturge Weber syndrome in association with oculo-dermal melanosis].
AB  - We present the case report of a 10 years old patient to whom, based on the
      clinical examination, lab and imaging studies we established the diagnosis.
      Sturge- Weber syndrome, oculo-dermal melanocytosis-right side. This case is
      interesting because of the unusual and rare association of these two diseases.

PMID- 18064953
TI  - [Pseudoexfoliative glaucoma].
AB  - The pseudoexfoliative syndrome is a systemic anomaly that primarily affects the
      eye. The presence of the pseudoexfoliative material causes important changes to
      the cornea, camerular angle, lens and zonules. Pseudoexfoliative glaucoma is
      aggressive, with great pressure differences between the two eyes, also with
      important circadian variations of intraocular pressure and has a poor prognostic.
      We present the case of a patient with pseudoexfoliative glaucoma.

PMID- 18064954
TI  - [Neuro-ophthalmologic relations in cervical syndrome].
AB  - In this article are reported three cases with ocular disturbances manifested by
      trophic keratitis, hypoesthesia of cornea and descemet precipitates. These
      disturbances have a connection with phenomenon caused by circulatory
      insufficiency within the territory of the vertebral artery, with involvement of
      the bulbo-protuberantial nuclei. The clinical manifestations are vestibular and
      visual disturbances, occipital headaches which means that the cervical
      sympathetic nerve was affected.

PMID- 18064955
TI  - [Anterior uveitis in a juvenile chronic arthritis, oligoarticular form].
AB  - We present the case of a 16-year-old male teen-ager admitted in the Ophthalmology
      Clinic Craiova, diagnosed with Anterior neglected acute uveitis in the left eye.
      Before and simultaneous with the ocular manifestations, the patient complained of
      pain on the hips joints. The pediatric examination, based on the clinical
      features and the laboratory findings, diagnosed him with Juvenile chronic
      arthritis, oligoarthritis type. The evolution was good under the corticosteroid
      therapy.

PMID- 18064956
TI  - [Retinal lesions in hereditary aplastic anemia].
AB  - We present a case report of a 6-year-old female child, admitted in the Pediatric
      Clinic, diagnosed with Aplastic Constitutional Hereditary Anaemia (Fanconi
      Anaemia). On ophthalmic examination, on the left eye were noted important macular
      edema and a big preretinal haemorrhage of 4 DP situated on the posterior pole.
      The treatment of the systemic condition established the involution of the
      ophthalmic manifestations.

PMID- 18064957
TI  - [Cone dystrophy].
AB  - In this issue we present the importance of OCT in the diagnosis of macular cones
      dystrophy.

PMID- 18064958
TI  - [Wyburn-Mason syndrome].
AB  - INTRODUCTION: The Wyburn-Mason or Bonnet, Dechaume, and Blanc syndrome is a rare
      congenital anomaly formed of malformations of the retinal vessels, orbito
      cerebral vessels, and, rarely, facial vessels. CASE REPORT: Male patient, 19
      years old, examined because of a severe visual loss and exophthalmos at the left
      eye. The ophthalmoscopic examination reveals extensive retinal arterio-venous
      malformations, also confirmed at orbito-cerebral level by ultrasound and MRI
      DISCUSSION: The Wyburn-Mason syndrome is due to arterio-venous anastomosis, being
      included in the phakomatosis group. Clinically we describe 3 groups of severity.
      Aspects of differential diagnosis, pathogeny, and treatment are discussed.
      CONCLUSIONS: The Wyburn-Mason syndrome can be suspected in cases of facial
      angioma, exophthalmos, or decreased visual acuity. The diagnosis imposes
      additional examinations with orbito-cerebral imagery.

PMID- 18064959
TI  - [Takayasu disease--case report].
AB  - Chronic vasculitis which determines the thickness of the affected arteries,
      Takayasu disease is an uncommon finding. It is characterized by narrowing of the
      big arteries beginning from the aortic arch. The result is arterial hypotension,
      cerebral and retinal ischemic signs, the absence of pulse at the upper limbs.
      Manifestations includes: vascular narrowing, microaneurysms, hemorrhages, cotton
      wool spots, vascular occlusions. The authors present the case of a 20-years old
      female patient with retinal vascular signs, admitted for ocular pain, upper limbs
      and mastication pains. The clinical examination revealed pulseless radial and
      brachial arteries, arterial pressure undetermined at both upper limbs.

PMID- 18064960
TI  - [The influence of ocular surgery for lacrimal secretion].
AB  - Dry eye syndrome remains a constant health problem while more and more patients
      are being involved and final data concerning the etiopathology is still missing.
      This study investigates the hypothesis that ocular surgery inflicts damage on the
      tear production (regarding quantity, quality or the compositional aspect). Ocular
      symptoms were registered with the help of a questionnaire. Lacrimal tests were
      applied before and after surgery at 6 weeks. Basic and reflex tear secretion was
      differentiated through Schirmer tests and tear quality was assessed with BUT.
      Proteomic analysis (global proteins, electrophoresis) and conjunctival biopsy was
      realized before surgery. Open eye surgery altered tear secretion in 91% of the 22
      patients examined.

PMID- 18064961
TI  - [Dry eye--etiopathogenic and histopathologic correlations].
AB  - AIMS: To assess the role of the common inflammatory mechanism in the pathogenesis
      of the dry eye syndrome. METHODS: 64 patients with eye surface symptoms were
      studied using a diagnostic algorithm: questionnaire (eye symptoms were graded and
      a symptomatology SCORE was calculated), objective eye examination (including
      Schirmer's test and the tear film breakup time-BUT). Histopathological
      examination of 14 conjunctival bioptic fragments was performed. RESULTS: 59.37%
      of the patients had a positive Shirmer's test, while only 23% tested positively
      for the BUT. No statistically significant correlation was established between
      Schirmer's test and the BUT or the symptomatology SCORE. There was a significant
      correlation between BUT and the symptomatology SCORE (p<0.05) and between BUT and
      the duration of the disease (p<0.01). The histopathological examination of the
      dry eye conjunctival samples evidenced the following alterations: loss of
      calyciforme cells, squamous metaplasia of the epithelium, subepithelial
      inflammation. CONCLUSIONS: The histological analysis confirms the implication of
      inflammation in the pathogenesis of the disease. The time of onset of the
      inflammation cannot be established, it may be initial or it may occur with the
      quantitative decrease of tears or with eye surface alterations.

PMID- 18064962
TI  - [Conjunctival stamp in diabetic patients].
AB  - The authors have suggested to reveal conjunctiva stamp changes in diabetic
      patients. A set of patients aged between 50 - 80 and having been diagnosed with
      diabetes mellitus were available for our study, therefore they have been
      ophthalmologically examined; both Schrimer and BUT tests have been performed. We
      removed conjunctiva stamps which, after being fixed and Giemsa stained, they were
      investigated by photonic microscopy. As to compare them we removed conjunctiva
      stamps from a group of control which was also Schrimer and BUT tested. RESULTS
      AND CONCLUSIONS: Both Schrimer and BUT tests pleaded for lacrimal hyposecretion
      in most of the diabetic patients; their conjunctiva stamps presented changes at
      the levels of both epithelial and calyciforme cells. Conjunctiva stamps were
      significantly changed in the old patients with a long lasted diabetes evolution
      pleading for the diagnosis of lacrimal hyposecretion syndrome (dry eye syndrome)
      in those patients.

PMID- 18064963
TI  - [Adaptometry in diabetic patients].
AB  - PURPOSE: To study the adaptometry's changes in diabetic patients MATERIAL AND
      METHODS: We studied the adaptometries in 3 groups of diabetic patients with
      different stages of retinal changes in diabetic retinopathy (DR). We used the
      Hartinger nyctometer We compared the results with normal adaptometries. RESULTS:
      We obtained photopic and scotopic changes of different intensity in correlation
      with fundus lesions due to DR. We found a correlation between the progression of
      DR and the adaptomery changes. We also noted changes in the adaptometry in
      patients with no fundus lesions but diabetes mellitus diagnosed for 7 or 10
      years. CONCLUSIONS: Diabetic retinopathy is a cause of changes in the
      adaptometry; this is an important issue for patients in choosing the occupation.

PMID- 18064964
TI  - [Central thickness of the cornea in ocular hypertension and open-angle glaucoma].
AB  - PURPOSES: To assess the necessity for corneal pachimetry in the primary open
      angle glaucoma (POAG) and ocular hypertension (OHT) diagnosis and follow-up. To
      establish a correlation between central corneal thickness (CCT) and glaucoma
      progression. METHOD: Retrospective study that included 199 eyes (108 patients)
      with POAG, normal tension glaucoma, OHT or glaucoma suspects. The evaluation
      included the intraocular pressure, CCT, C/D ratio and visual field (standard
      automated perimetry). For the patients that had performed at least 3 visual
      fields we have searched the perimetric progression of glaucoma and we have noted
      the mean lOP throughout the follow-up period. RESULTS: The mean CCT was higher in
      OHT (559.28 +/- 26.35 m) than in POAG (542.83 +/-31.07 microm). In the 10 cases
      of newly diagnosed OHT the CCT has influenced the diagnosis (the OHT with a high
      risk of progression to glaucoma was assigned to antiglaucoma treatment). 57 eyes
      had at least 3 visual fields. The Kaplan-Meyer survival analysis showed that the
      eyes with CCT 520 m had significantly earlier glaucoma progression ( the mean IOP
      was 17.59 +/- 2.33 mmHg, compared to 18.28 +/- 1.55 mmHg in the eyes with CCT>
      520 m, p = 0.36). CONCLUSIONS: The central corneal thickness is significantly
      higher in eyes with ocular hypertension than in those with POAG. In eyes with
      thin cornea the glaucoma progression tends to appear earlier, which suggests a
      need for lower target IOP in these cases.

PMID- 18064965
TI  - [Ophthalmologist and "computer vision syndrome"].
AB  - The authors had tried to collect the data available on the Internet about a
      subject that we consider as being totally ignored in the Romanian scientific
      literature and unexpectedly insufficiently treated in the specialized
      ophthalmologic literature. Known in the specialty literature under the generic
      name of "Computer vision syndrome", it is defined by the American Optometric
      Association as a complex of eye and vision problems related to the activities
      which stress the near vision and which are experienced in relation, or during,
      the use of the computer. During the consultations we hear frequent complaints of
      eye-strain - asthenopia, headaches, blurred distance and/or near vision, dry and
      irritated eyes, slow refocusing, neck and backache, photophobia, sensation of
      diplopia, light sensitivity, and double vision, but because of the lack of
      information, we overlooked them too easily, without going thoroughly into the
      real motives. In most of the developed countries, there are recommendations
      issued by renowned medical associations with regard to the definition, the
      diagnosis, and the methods for the prevention, treatment and periodical control
      of the symptoms found in computer users, in conjunction with an extremely
      detailed ergonomic legislation. We found out that these problems incite a much
      too low interest in our country. We would like to rouse the interest of our
      ophthalmologist colleagues in the understanding and the recognition of these
      symptoms and in their treatment, or at least their improvement, through
      specialized measures or through the cooperation with our specialist occupational
      medicine colleagues.

PMID- 18064966
TI  - [Corneal preservation at 34 degrees C in CO2 enriched atmosphere].

PMID- 18064967
TI  - Preliminary report on the Accountability Scale: a change and outcome measure for
      intimate partner violence research.
AB  - The current study investigated the reliability of a new self-report questionnaire
      assessing accountability for the perpetration of intimate partner violence. The
      Accountability Scale (AS) is a brief, Likert-type measure designed to assess the
      degree to which perpetrators acknowledge and accept responsibility for their
      violent actions. In Study #1, an exploratory factor analysis on a clinical sample
      revealed two factors: Acknowledging Harm and Internalizing Responsibility. In
      Study #2, the factor structure was replicated on a community sample using
      confirmatory factor analysis, revealing an 11-item solution. Factor 1 was related
      to readiness to change but negatively related to social desirability, suggesting
      convergent and discriminant validity of that subscale. Factor 2 was negatively
      related to Factor 1 in the community sample, calling into question the construct
      of accountability. Preliminary evidence suggests that the AS shows promise as a
      brief and reliable tool to assess forms of accountability. Future research will
      examine if the two factors of accountability function as mechanisms of change and
      outcome measures in intimate partner violence intervention research.

PMID- 18064968
TI  - Female domestic violence offenders: their attachment security, trauma symptoms,
      and personality organization.
AB  - Unlike male domestic violence offenders, female domestic violence offenders have
      traditionally been overlooked in research and theory, despite the fact that
      females also have high rates of domestic violence perpetration. Towards the aim
      of extending extant research on male and female pepetrators of domestic violence,
      we examined attachment style, trauma symptoms, and personality organization in 33
      female offenders receiving mandated treatment for domestic violence. These
      offenders were compared to 32 nonoffending women receiving psychological
      treatment. The Experiences in Close Relationships Revised (ECR-Revised) was used
      to examine adult attachment, the Trauma Symptom Inventory (TSI) was used to
      examine trauma symptomology, and finally, the Millon Clinical Multiaxial
      Inventory III (MCMI-III) was used to examine cluster B personality traits.
      Analyses indicated that female domestic violence offenders reported less
      attachment security, more trauma-related symptoms, and more personality
      psychopathology (Antisocial, Borderline, and Dependent Subscales) than did
      nonoffender clinical comparison women.

PMID- 18064969
TI  - The impact of partner stalking on mental health and protective order outcomes
      over time.
AB  - The goals of this article are to examine stalking victimization over time among a
      large sample (n = 662) of women who received a protective order against a violent
      partner and to examine the impact of stalking on mental health and protective
      order outcomes. Findings suggest that stalking is a significant risk factor for
      other forms of partner violence (e.g., psychological, physical, and sexual
      violence) and that the experience of being stalked by a violent partner
      contributes uniquely to women's perceptions of psychological distress, personal
      safety, and perceptions of protective order effectiveness. Both the criminal
      justice system and victim service representatives need to be vigilant in
      educating women about the increased risk of stalking to their safety and mental
      health. Further, study findings suggest that stalking must be addressed to
      prevent future physical and psychological harm in partner violence cases.

PMID- 18064970
TI  - Perceptions of motives in intimate partner violence: expressive versus coercive
      violence.
AB  - This study examined perceptions of motives in the perpetration of intimate
      partner violence. Respondents (N = 401) of diverse professions read three
      vignettes and indicated their perception of the aggressor's motive (from 1 =
      Exclusively Expressive; 5 = Exclusively Coercive). Half of respondents read
      vignettes describing male-perpetrated violence against a female partner; the
      other half, female-perpetrated violence against a male partner. Overall, male
      perpetrated aggression was seen as more coercive than female-perpetrated
      aggression, particularly by shelter workers and victim advocates. Further
      analyses revealed that men generally gave higher ratings than women, and that
      women rated female-perpetrated aggression as less coercive than male-perpetrated
      aggression. In contrast, men did not differ in their ratings of male versus
      female perpetration. Implications are discussed with respect to the assessment
      and treatment of partner violence.

PMID- 18064971
TI  - Family environment and adult attachment as predictors of psychopathology and
      personality dysfunction among inpatient abuse survivors.
AB  - The current study explored the role of early family environment and adult
      attachment style in explaining long-term outcomes among child abuse survivors.
      Adult patients (N = 80) in a trauma treatment program were assessed for clinical
      diagnosis and administered a multiscale questionnaire. Hierarchical regression
      analyses were significant for dissociative identity disorder (DID), substance
      abuse, anxiety disorder, posttraumatic stress, somatization, and six personality
      disorder dimensions. Adult attachment styles were significant predictors of most
      outcome variables. Of particular note was the strong contribution of attachment
      avoidance to DID. Five family environment scales (Independence, Organization,
      Control, Conflict, Expressiveness) also contributed to various psychopathological
      outcomes. Evidence emerged supporting a mediating role for attachment style in
      the link between family independence and five personality disorder dimensions.

PMID- 18064972
TI  - Covictims of capital murder: statements of victims' family members and friends
      made at the time of execution.
AB  - The death penalty is often touted as a punishment providing the only way to truly
      serve justice and offer closure for covictims (defined as family members or
      friends of murder victims'). These rationales are rarely structured around the
      actual words of these individuals, however. The findings in this study suggest
      that such rhetoric oversimplifies and often misrepresents the experiences and
      perspectives of covictims. Through their own words, we learn that the death
      penalty is not always the soothing salve for the pain and suffering of covictims
      we wish it to be. Rather, we find much more ambivalence and complexity in the
      statements of covictims. The impact of the death penalty and executions on
      covictims and their ability to attain healing and closure is not so clear cut. By
      presenting the actual words of capital murder covictims at the time of execution,
      this inductive, exploratory study provides a novel glimpse at the perspectives of
      these individuals and their perception of the death penalty process.

PMID- 18064973
TI  - Exposure to child abuse and risk for mental health problems in women.
AB  - Risk for adult mental health problems associated with child sexual, physical, or
      emotional abuse and multiple types of child abuse was examined. Logistic
      regression analyses were used to test study hypotheses in a population-based
      sample of women (N = 3,936). As expected, child sexual, physical, and emotional
      abuse were independently associated with increased risk for mental health
      problems. History of multiple types of child abuse was also associated with
      elevated risk for mental health problems. In particular, exposure to all three
      types of child abuse was linked to a 23-fold increase in risk for probable
      posttraumatic stress disorder (PTSD). Findings underscore relations between child
      emotional abuse and adult mental health problems and highlight the need for
      mental health services for survivors of multiple types of child abuse.

PMID- 18064974
TI  - Prevalence, perpetrators, and characteristics of witnessing parental violence and
      adult dating Violence in Latina, East Asian, South Asian, and Middle Eastern
      women.
AB  - The present study describes and compares the prevalence, perpetrators, and
      characteristics of witnessing parental violence during childhood and experiencing
      adult relationship violence in 251 college-educated South Asian/Middle Eastern (n
      = 93), East Asian (n = 72), and Latina (n = 86) women residing in the United
      States. Results showed that more than 50% of each ethnic group witnessed parental
      and adult relationship violence. For all three groups, adult psychological
      violence was more prevalent than physical violence, which, in turn, was more
      prevalent than injury violence. Significant differences were found for paternal
      and maternal psychological, physical, and injury violence witnessed within ethnic
      groups. High prevalence rates and significant differences emerged for
      psychological, physical, and injury violence experienced as a victim and enacted
      as a perpetrator within ethnic groups. The implications of college-educated,
      higher socioeconomic status (SES) women of color being at risk for witnessing and
      experiencing family violence are discussed.

PMID- 18064975
TI  - Peer tutoring for college students with learning disabilities: perceptions of
      tutors and tutees.
AB  - Peer tutoring is a commonly provided support service for students with learning
      disabilities (LD) in institutions of higher education. A large-scale survey was
      conducted to evaluate the PERACH peer tutoring project for students with LD at 25
      universities, regional colleges, and teacher training colleges in Israel. The
      purpose of the study was to understand the tutoring process from the point of
      view of both tutees and tutors with respect to 5 main areas: tutees' needs, focus
      of tutoring activities, difficulties surrounding the tutoring endeavor,
      importance of similar study experiences, and satisfaction with the project. It is
      our supposition that major discrepancies in perceptions are likely to undermine
      the effectiveness of the tutoring. Similarities and differences in perceptions
      were identified, and implications that can be useful in guiding service providers
      are discussed.

PMID- 18064976
TI  - Self-efficacy from the perspective of adolescents with LD and their specialist
      teachers.
AB  - This study used qualitative methodology to investigate the self-efficacy beliefs
      of early adolescents with learning disabilities (LD). We conducted a series of
      focus group interviews with 28 Grade 8 and 9 students with LD and individual
      interviews with 7 specialist LD teachers. Content analyses of the student and
      teacher data resulted in 2 a priori and 3 inductive themes: self-efficacy,
      calibration and levels of self-efficacy, students' self-awareness, attributions
      for failure, and problems and solutions. The students viewed themselves as low in
      self-efficacy and generally accurate in the calibration of their efficacy and
      performance, whereas the teachers viewed the students as overconfident about
      academic tasks. In contrast to the teachers, the students viewed verbal
      persuasion as a valued source of self-efficacy. Students attributed their
      failures to lack of effort, whereas their teachers attributed student failure to
      uncontrollable deficits. Problems and solutions related to student motivation
      were discussed from student and teacher perspectives.

PMID- 18064977
TI  - Effectiveness of paraeducator-supplemented individual instruction: beyond basic
      decoding skills.
AB  - A total of 46 children in Grades 2 and 3 with low word-level skills were randomly
      assigned to 1 of 2 groups that received supplemental phonics-based reading
      instruction. One group received intervention October through March (21.5 hours),
      and one group served as a control from October through March and later received
      intervention March through May (17.5 hours). Paraeducators trained in a standard
      treatment protocol provided individual instruction for 30 min per day, 4 days per
      week. At the March posttest, the early treatment (ET; n = 23) group outperformed
      the controls (late treatment, LT; n = 20) on reading accuracy and passage
      fluency. Across both groups, second graders outperformed third graders on these
      same measures. At the 3-month follow-up, the ET group showed no evidence of
      decline in reading accuracy, passage fluency, or words spelled; however, 3rd
      grade ET students had significantly higher spelling skills compared to 2nd
      graders. The LT group demonstrated significant growth during their intervention
      in reading accuracy and spelling, but not passage fluency. When we compared the
      ET and LT groups on their gains per instructional hour, we found that the ET
      group made significantly greater gains than the LT group across all 3 measures.
      The results support the value of paraeducator-supplemented reading instruction
      for students below grade level in word identification and reading fluency.

PMID- 18064978
TI  - Why are students with LD depressed? A goal orientation model of depression
      vulnerability.
AB  - The thesis of the present study was that failure in achievement tasks may
      constitute a stress factor that can trigger a depression episode, particularly
      for students with learning disabilities (LD), and that a particular motivational
      pattern may constitute a cognitive diathesis for depression. Participants were
      104 students referred for LD who were drawn from a pool of approximately 900
      students from Grades 5 and 6. Students were challenged with a series of difficult
      math exercises, and their achievement behaviors were examined as a function of
      achievement goal orientations. Results from structural equation modeling provided
      empirical support of the contention that performance-avoidance goals may account
      for a series of negative cognitions and affect. Direct positive paths linked
      performance-avoidance goals to anxiety, depression, and negative affect; negative
      paths were revealed with regard to self-esteem and positive affect. Thus,
      performance-avoidance goals may possess elements of the diathesis mechanism
      described by Dykman, constituting a vulnerability factor that triggers the
      mechanism of depression when negative events are in place.

PMID- 18064979
TI  - Teaching students with LD to use diagrams to solve mathematical word problems.
AB  - This study examined the effectiveness of instruction focused on teaching students
      with learning disabilities (LD) to solve 1- and 2-step word problems of varying
      types. Three students with LD in Grade 8 participated in the study. During the
      treatment, students received instruction in diagram generation and a strategy
      that incorporates diagrams as a part of the procedure to solve word problems. The
      results indicated that all students improved in the number of diagrams they used
      and in their ability to generate diagrams. Their word problem solving performance
      increased. Moreover, the students generated and used diagrams to solve other
      types of problems. Overall, the students were very satisfied with the instruction
      and would continue to use the diagrams and the strategy to solve word problems in
      other classroom settings.

PMID- 18064980
TI  - Mathematical ability of 10-year-old boys and girls: genetic and environmental
      etiology of typical and low performance.
AB  - The genetic and environmental etiologies of 3 aspects of low mathematical
      performance (math disability) and the full range of variability (math ability)
      were compared for boys and girls in a sample of 5,348 children age 10 years
      (members of 2,674 pairs of same-sex and opposite-sex twins) from the United
      Kingdom (UK). The measures, which we developed for Web-based testing, included
      problems from 3 domains of mathematics taught as part of the UK National
      Curriculum. Using quantitative genetic model-fitting analyses, similar results
      were found for math disabilities and abilities for all 3 measures: Moderate
      genetic influence and environmental influence were mainly due to nonshared
      environmental factors that were unique to the individual, with little influence
      from shared environment. No sex differences were found in the etiologies of math
      abilities and disabilities. We conclude that low mathematical performance is the
      quantitative extreme of the same genetic and environmental factors responsible
      for variation throughout the distribution.

PMID- 18064981
TI  - [Sexual dysfunction after colostomy].
AB  - BACKGROUND: Sexual disturbances after colostomy are various. However, they
      probably remain underestimated in societies where sexuality is still a taboo
      issue. THE AIM of this prospective study was to evaluate the possible sexual
      behaviour and the post operative sexual disturbances in patients whome underwent
      colostomy. METHODS: The group was devided in 10 male and 11 female patients.
      Seventeen patients (81%) were married, 3 widowed and 1 unmaried. RESULTS: Sexual
      disturbances were found in 47% of patients. There was a lack of interest in
      sexual relations in 2 women, a resolved premature ejaculation in one case, post
      operative dysparenia in 2 female patients, a retrograde ejaculation in a 60-year
      old man, impotence in a 46 years old patient, and a premature ejaculation in a 36
      year-old man. The frequency of sexual disturbances (47%) in our series was close
      to that reported in the literature (50%). CONCLUSION: The sexual disorders are
      more common in male patients, the most frequent being ejaculatory dysfunction. In
      women, dyspareunia is the most common disorder. The particular case of colostomy
      in homosexuals remains a current issue.

PMID- 18064982
TI  - [Scintigraphic preoperative localization of abnormal parathyroid gland].
AB  - THE AIM of this study is to evaluate the accuracy of scintigraphic preoperative
      localization of abnormal parathyroid gland. METHODS: 25 patients with confirmed
      hyperparathyroidism undergone scintigraphic and ultrasound localization prior to
      surgery. Paratthyroid scintigraphy was done with thallium - techetium
      substraction and technetium-tetrofosmin dual phase techniques. RESULTS:
      scintigraphic sensitivity and specificity was 83% and 100%. In primary
      hyperparathyroidism the sensitivity was 91% vs 75% in secondary one. Multinodular
      goiter affected sensitivity (72%). Ultrasound had an overall sensitivity of 66 %
      and a specificity of 100%. CONCLUSION: parathyroid scintigraphy is non invasive,
      accurate and costeffective in localizing abnormal parathyroid gland especialy
      adenoma.

PMID- 18064983
TI  - [Utility of joint distension during arthrography in treatment of adhesive
      capsulitis of the shoulder in a study of 20 patients].
AB  - AIM: The aim of our study is to evaluate the efficacy of joint distension during
      arthrography followed by an intra articular corticosteroid injection. METHODS:
      This procedure associated to a physical therapy started immediately after joint
      distension and performed during 3 months in the treatment of 20 patients
      suffering from adhesive capsulitis of the shoulder were assessed. RESULTS:
      Patients were evaluated on D 90:90 % of them have regression of pain, 70 % have
      an improvement of deficiency and ranges of motion of the shoulder. Adhesive
      capsulitis of the shoulder is a disabling pathology but, generally, with good
      evolution. It is a clinical diagnosis. CONCLUSION: Joint distension associated to
      physical therapy has an interest in treatment because of therapeutic and antalgic
      effect and also restoration of range of movement.

PMID- 18064984
TI  - [Common lumbosciatic syndrome of the elderly. Report of 67 cases].
AB  - BACKGROUND: The common lombosciatic is a disease observed at all ages. To the
      elderly, clinical data, treatment, clinical outcome and prognosis present
      sometimes some peculiarities. AIM: Report of lombosciatic in the elderly.
      METHODS: It is a retrospective study including 67 cases of sciatica concerning
      old patients over 65 years presenting with common lombosciatica, hospitalized
      between January the 1-st, 2000 and December 31 st, 2004. RESULTS: The mean age of
      our patients is of 71.2 years, sex ratio female/male of 1.88. A chronic lumbago
      is found at 16.34% of our patients and a starting factor pains in 14.3% of cases.
      Pain is of progressive installation in 93.4 % of cases. Mechanical in 77.5 % of
      cases and impulsive in 55 % of cases. Sciatica was unilateral in 67.3% of cases
      and interesting the root L 5 in 40.8 % of cases. Physical exam find a painless
      attitude in 26.5% of cases and a spasm of spinal muscles in 65.3%. The average of
      schober index is of 2.4 cms + 1.18. Lasegue is present in 36.7 % of cases.
      Neurological exam find overdrawn signs in 8 % of cases, sensory signs in 61.2% of
      cases. No cauda equine syndrome was individualized in our series. Lumbar spine X
      rays, made in 98 % of cases, show a L5-S1 disc impairment in 83.6% of cases, a
      scoliotic attitude in 22.4 % of cases, a spondylolithesis of L4L5 in 26,5 % of
      cases and lumbar cannal stenosis in 12.2% of cases. Lumbar densitometry, realized
      in 22.4% of cases, shows a herniated disc in 27.2% of cases, and a lumbar canal
      stenosis in 27.2% of cases. The MRI, made once, was normal. During their
      hospitalization, 87.7% of patients received NSAID's, 18.4% of them analgesics
      drugs (landing I, II , III) and 79.6 % epidurals infiltrations. All our patients
      observed bed rest. A physiotherapy was prescribed for 44.9 % of them. A good
      outcome was quickly noticed in 85.7% of the patients. A therapeutic failure was
      observed at 14.3 %. 6% underwent surgery. Only 102 % of the non operated patient
      had pain recurrence. CONCLUSION: Nowadays sciatica is a frequent pathology either
      in oung or in geriatric population. Nevertheless it is necessary to eliminate a
      tumoral or infectious sciatica that can be misleading by the condition of the old
      age and by the frequent associated pathologies at such age.

PMID- 18064985
TI  - [Chronic heart failure: role of Doppler echocardiography in the evaluation of
      mortality risk].
AB  - BACKGROUND: Chronic heart failure (CHF) is a major cause of morbidity and
      mortality. Despite recent improvements in the management of this condition, the
      overall prognosis remains poor. Echocardiography is the most useful test in the
      evaluation of systolic and diastolic function and has also a prognostic value.
      AIM: The aim of this study is to determine echocardiographic predictors of
      mortality in patients with CHF. METHODS: We followed 100 patients with a
      diagnosis of CHF over an average period of 44+/-40.5 months. We compared
      echocardiographic parameters in survivors and non survivors. RESULTS: Four
      variables predicted death: LVEF <35% (p=0.001), TDE <150ms (p=0.001), E/A ratio
      >2 (p=0.05) and E/Ea ratio >10 (p=0.008). CONCLUSION: Doppler echocardiography
      has a central role in the evaluation of patients with CHF. It provides valuable
      prognostic information by combination of several parameters.

PMID- 18064986
TI  - [Adenomyosis at hysterectomy].
AB  - BACKGROUND: adenomyosis is a frequent gynecologic pathology which affects women
      particularly in the fifth decade. It is responsible of abnormal uterine bleeding
      and pelvic pain. The diagnosis can be difficult especially when it's associated
      to other gynaecologic pathologies. Contribution of transvaginal sonography and
      magnetic resonance imaging made preoperative diagnosis possible. THE AIM of this
      study is to report frequency, epidemiologic profile, clinical signs and
      diagnostic and therapeutic methods of adenomyosis. METHODS: this is a
      retrospective study about 52 cases of adenomyosis diagnosed upon 336
      hysterectomies for benign pathologies. Descriptive analysis of epidemiologic,
      clinical, diagnosis and therapeutic data was performed. RESULTS: prevalence of
      adenomyosis was 15% and multiparity observed for 90% of women was the main risk
      factor. CONCLUSION: women desirous of pregnancy and affected by adenomyosis can
      benefit from conservative treatment, but hysterectomy remains the reference
      treatment.

PMID- 18064987
TI  - [Digestive polyposis. Retrospective study of 20 cases].
AB  - BACKGROUND: Three main polyposis syndromes are transmitted as an autosomal
      dominant disorder: familial adenomatous polyposis (FAP), juvenile polyposis
      syndrome (JPS) and Peutz-Jeghers syndrome. AIM: Evaluate this management of
      digestive polyposis. METHODS: Our study included 20 patients which were collected
      in th departements of pathology surgery and garstroenterology of MT Maarmouri's
      Hospital, Nabeul city. RESULTS: We reported 15 cases of adenomatous polyposis
      with 2 family groups. We identified a family group of JPS with 3 members and 2
      cases of Peutz-Jeghers syndrome. We found 11 cases of colonic adenocarcinoma out
      of the 15 patients affected by adenomatous polyposes. FAP is a generalized
      disorder involving the entire colorectum segment with numerous extra-colonic
      manifestations. The risk to develop colonic cancer is 100%. JPS is characterised
      by the development of numerous gastrointestinal juvenile polyps and occurs
      usually before 20 years old, the progression to cancer is rarely observed.
      CONCLUSION: Peutz-Jeghers syndrome consists in hamartomatous polyps associated to
      a characteristic mucosal pigmentation. The patients are usually young adults and
      have an increased incidence of cancer in extradigestive sites.

PMID- 18064988
TI  - [Azathioprine for prevention of postoperative recurrence in Crohn's disease].
AB  - BACKGROUND: Crohn's disease is a chronic inflammatory bowel disease that can
      involve any portion of the gastrointestinal tract. Up to 74% of patients require
      surgery. However, although resective surgery improves the clinical situation,
      relapses is frequent in most cases. THE AIM of this clinical trial was to
      evaluate the profile of patient who received AZA after surgical treatment in
      order to prevent postoperative recurrence. METHODS: This was a retrospective
      study including 17 patients with severe Crohn's disease attending our
      gastrointestinal unit from September 1998 to June 2004. Patients were eligible if
      they have severe Crohn's disease, undergoing curative surgical treatment and
      received azathioprine for the first time after surgery to prevent postoperative
      recurrence. RESULTS: The study population comprised 17 patients with Crohn's
      disease (10 men and 7 women; mean age, 27 years). The Crohn's disease was ileo
      colic in 10 cases with perineal manifestations for 2 patients and ileal in 7
      cases. The indications for surgery were stenosis in 10 cases, fistula in 5 cases,
      perforation in 1 case and corticosteroid-resistance in 1 case. The median
      following-up period was 40 months (9-80 months). During this period, only 1
      patient reported severe adverse event and discontinued treatment due to acute
      pancreatitis. 1 patient was lost to follow-up and 3 patients had moderate
      clinical relapse. Maintained remission was obtained for 12 patients. None of our
      patients had surgical relapse. CONCLUSION: The result of this study shows the
      effect of Azathioprine in preventing both clinical and surgical relapses in
      patients with Crohn's disease who have undergone surgery.

PMID- 18064989
TI  - [Intralesional and anatomopathologic features of psoriatic erythroderma].
AB  - BACKGROUND: Psoriasis is a chronic inflammatory cutaneous disorder. It is marked
      by aberrant epidermal and dermal expression of cytokines. AIM: Evaluate the
      expression of proinflammatory cytokines in a particular severe form of psoriasis
      the psoriatic erythroderma. METHODS: We focused on intra-lesional cytokine gene
      expression in cutaneous biopsies of lesional site and their correspondent non
      lesional skin. On the whole, four healthy volunteers and thirty six patients were
      included in this study. Among these, three had a psoriatic erythroderma. Assuming
      that local production of cytokines may be approached by mRNA cytokine
      quantification, the expression of alpha tumour necrosis factor (TNFalpha) and
      interleukin-8 (IL-8) was analyzed by reverse transcription and real time
      quantitative polymerase chain reaction. RESULTS: Under expression of all selected
      molecules in psoriatic erythroderma lesions was contrasted with the data obtained
      in the other psoriatic lesion forms witch revealed that ratios had significantly
      increased in lesional skin compared with non lesional one. However, at anatomy
      pathology analysis, inflammatory infiltrate in psoriatic erythroderma was
      classical poor and no specific of this disease, such as the case of our three
      patients. This could explain the drop of intra-lesional inflammatory mediators.
      CONCLUSION: The paradoxal low levels of proinflammatory cytokines in psoriatic
      erythroderma are an original and important result.

PMID- 18064990
TI  - [Epidemiology of work-related eye injuries].
AB  - BACKGROUND: Occupational injury represents 7,7 at 69,9% of the total ocular
      traumatisms. They can be a major source of visuel loss and blindness. The aim is
      to study the epidemiology of work-related ocular injuries: objects
      frequencies,works most exposed. METHODS: We performed a prospective study that
      interest 78 patients having a work-related ocular traumatism during a 4 months
      period. They were admitted at ocular emergeney All patients underwent an
      ophtalmologic examination completed with orbital radiography and echography. A
      medical and/or chirurgical appropriate treatment was institued. RESULTS:
      Occupationnal injury frequency was 9% of the whole ocular traumatisms in the same
      period. The mean age was 31 years. 55% of cases were under 30 years. 91% were
      male. Most exposed works were industrial and mecanical sectors In 70,5% of cases
      work-related eye injuries were caused by projectile objects. Most common lesion
      was corneal superficial foreign body (58%). Open globe injury was noted in 8%.
      95% of patients had no eye protection at the time of the accident. 13% were blind
      or unilateral partially sighted (according to the OMS classification).
      CONCLUSION: The authors discussed the importance and different prevention
      strategies to prevent the risk of blindness and socio-economical cost of
      occupationnal accidents. There is a need for systematic periodic sensibilization
      to reduce these accidents and blindness.

PMID- 18064991
TI  - [Treatment of painful bony metastases with Samarium 153-EDTMP in prostate
      carcinoma].
AB  - THE OBJECTIVE of this work is to evaluate a new therapy, the metabolic
      radiotherapy to the 153Samarium-EDTMP, of recent introduction in Tunisia, in the
      painful bony metastasis treatment observed at the patients affected of cancer of
      the prostate. METHODS: It is about a retrospective survey with a receding of 40
      months, achieved through 45 files of patients having benefited all of this new
      treatment for painful bony metastases in relation with a prostatic adenocarcinoma
      and collected by three centers of Nuclear Medicine of the capital: the institute
      Salah Azaiez (state-controlled), the Center CERU (deprives) and the Military
      hospital (HMPIT). RESULTS: We tried to appreciate essentially four parameters:
      the therapeutic efficiency, the factors influencing the answer in the treatment,
      the toxicity of the treatment and the sources of failure. We observed a positive
      answer in 92,1% of the cases, this answer was complete in 36,5% of the cases. The
      results gotten after multiple administrations show that the cures could be
      repeated with results comparable to those of the first cure. The therapeutic
      efficiency is at least equivalent to those of the other therapeutic means, with
      nearly non-existent secondary effects. The only toxicity is of hematological
      order; it is the most often moderate and reversible with a complete recuperation
      at the end of 8 weeks. Besides, the effect on the pain came with an improvement
      of the quality of life of the patients treaties. CONCLUSION: Its precocious
      introduction in the taken in charge of the metastatic patients, would allow them
      to benefit better from its efficiency, simplicity and weak toxicity and therefore
      to enjoy a better quality of life.

PMID- 18064992
TI  - [Results of unicondylar femoral fractures: a review of 28 patients].
AB  - BACKGROUND: Unicondylar femoral fractures are rare. They form a particular entity
      of the femoral lower extremity fractures. THE PURPOSE of this work was to
      evaluate the anatomical and functional results of unicondylar femoral fractures
      on pain, mobility, walking and stability of the knee. METHODS: We reviewed,
      retrospectively, 28 patients presenting unicondylar femoral fracture. There were
      19 men and 9 women, with average age of 54 years (22 - 87 years), victims
      essentially of domestic accident. The fracture was alone in 65 % of cases.
      According to Nordin's classification, the fracture was of type I in 3% of cases,
      type II in 35 % of cases, type III in 20 % of cases and type IV in 42 % of cases.
      Twenty five patients had a surgical treatment after a median period of 7 days
      post-accident, 3 patients were treated orthopedically. RESULTS: After 3 years
      follow up, results were noted according to MEGY's score which takes into account
      walking, mobility, pain and the stability. Clinically, we noted 26 good and very
      good results and 2 moderate results. Anatomically, we obtained 75 % of
      satisfactory reductions. CONCLUSION: Unicondylar femoral fractures remain rare.
      It is important to recognize them and to make the exact diagnosis of their type.
      Surgical treatment exposes old subjects to risk of dismantling anatomical
      osteosynthesis because of osteoporoses.

PMID- 18064993
TI  - Primary leiomyosarcoma of broad ligament.
AB  - BACKGROUND: Primary broad ligament leiomyosarcoma (LMS) is an extremely rare
      tumor with few well-documented cases. We are aware of 15 previously reported
      observations. AIM: Report of a new case. CASE: In this report we report a case of
      a right pelvic sidewall leiomyosarcoma with involvement of the appendix in a 49
      year-old woman. A hysterectomy, bilateral salpingo-oophorectomy, omentectomy and
      appendicectomy were done, without complications. The patient died five months
      later. The case illustrates the difficulty of correct diagnosis before
      intervention. On this occasion, review of the literature confirms that this site
      remains unusual and the management is difficult.

PMID- 18064994
TI  - [Phlegmonous appendicitis revealed by pyogenic liver abscesses].
AB  - BACKGROUND: Pyogenic liver abscesses are rare and severe. Early diagnosis and
      treatment lead to a better prognosis. Biliary cause of liver abscesses is the
      most frequent. Portal origin is secondary to a portal bactremia. Appendicitis was
      the most cause of portal infection, but actually, diverticulitis is most common.
      AIM: the aim of this study was to report a new case of pyogenic liver abscesses
      secondary to phlegmonous appendicitis. CASE REPORT: We report a case of 47 years
      old man presented with fever and weight loss without abdominal pain. Laboratory
      investigations show signs of inflammation with high leukocyte and neutrophile
      rates. The diagnosis of liver abscesses was made on abdominal ultrasound and
      tomodensitometry witch shows also an inflammatory appendix. The outcome was good
      after antibiotics associated with percutaneous drainage of abscesses and
      laparoscopic appendectomy witch found a phlegmonous appendix. One month later,
      the CT scan showed a markedly decrease of the size of the abscesses.

PMID- 18064995
TI  - Aortic endocarditis complicated with a large ventricular septal defect and septic
      pulmonary embolism.
AB  - BACKGROUND: Infectious complications of the aortic valve can lead to severe
      cardiac failure and widespread contiguous lesions by the involvement of subaortic
      structures such as aorto-left ventricular discontinuity, destruction of the
      aortic ring, aortic abscesses, true or false aneurysms and shunts. AIM: Report a
      new case of a large ventricular septal defect due to infection. CASE REPORT:
      Abnormal communications occurring during acute aortic valve endocarditis are rare
      but they are very serious complications. We report a case of a 58 year-old-man,
      referred to our hospital with the diagnosis of aortic endocarditis with
      complicating root abscesses, acquired ventricular septal defect (VSD) and
      pulmonary septic embolism. Surgery was indicated and the whole procedure was
      performed through the aortic root. The patient underwent a radical resection of
      the abscesses, reconstruction of the aortic ring, closure of the ventricular
      septal defect and prosthetic replacement of the aortic valve. The immediate
      postoperative course was marked by persistent sepsis. Transoesophageal
      echocardiography showed vegetation's in the right side of the patch without signs
      of dehiscence. The outcome was fatal due to hemodynamic collapse. CONCLUSION: The
      authors would like to select and analyze some weaknesses of their procedure like
      using only the transaortic access that often limits exposure of possible right
      side lesions, not removing the pulmonary obstruction and using an important
      amount of foreign material to reconstruct subvalvular lesions.

PMID- 18064996
TI  - [Primary carcinoid tumors of the ovary. Report of three cases].
AB  - BACKGROUND: Carcinoides tumours are a rare type of ovarian tumours which
      anatomoclinical behaviour differs a little from epithelial type. AIM: Report of
      three new cases. CASE REPORT: We report 3 observations of ovarian carcinoid
      tumours in patients aged 50, 23 and 28 years. All our patients were operated in
      emergency for twisting of appendix in two patients and for acute peritonitis in
      the third one. Treatment was a one-sided salpingo-oophorectomy. The diagnosis of
      carcinoid tumour was retained on to the definitive histological exam then the
      patients were re operated to complete the resection.

PMID- 18064997
TI  - [Synchronous association of ileal carcinoid and colorectal carcinoma. A case
      report].
AB  - BACKGROUND: Multiple primary malignant neoplasms in a single patient have been
      well documented in the literature. The lesions can be limited to a single organ
      or involve multiple organ systems and can be synchronous or metachronous. AIM:
      Report of a new case. CASE REPORT: We report the case of a 63 year old women with
      a rectocolonic carcinoma; during surgery an ileal nodule was discovered also as
      liver metastasis. The final pathologic report on the specimen revealed an
      adenocarcinoma of the colon and a carcinoid tumor of the small bowel with liver
      metastasis. Tumoral association is relatively common for patients with small
      intetinal carcinoids. CONCLUSION: The association carcinoide of hail with
      primitive tumour not carcinoide is reported primarily with carcinomes of the
      digestive tract in particulary recto colics carcinoma.

PMID- 18064998
TI  - [Acute hyperlipemic pancreatitis (2 cases)].
AB  - THE AIM of this work was to study the clinical and therapeutic features of this
      affection. CASE REPORT: Our retrospective study concerned two cases of
      hyperlipemic pancreatitis treated during 6 years from 1998 to 2003. The incidence
      of this affection was 1.42%. Our patients were respectively a man aged 32 years
      without any significant history and a pregnant woman aged 24 years with a
      positive history of dyslipidemia. Clinical, biologic and radiological data didn't
      differ from those of other causes of acute pancreatitis. The hyperlipemic origin
      was confirmed by a lactescent serum and a rate of triglycerides greater than 10
      g/l. The course was characterized by the recurrence of pancreatitis related to
      the increased triglycerid serum level over 10 g/l. Plasmapheresis and
      administration of heparin and/or insulin seem to be efficient in reducing the
      serum level of triglyceride and in improving the course. Hygieno-dietary measures
      and hypolipemiant treatment were necessary for the level of triglyceirdes in
      serum below 10 g/l. We in the absence of comolicatons, surgery seemed umnecessry
      in the two cases. CONCLUSION: the clinical pattern of acute hyperlipemic
      pancreatitis doesn't include any specific elements, but its treatment and
      prevention must take into account the associated hyperlipidemia.

PMID- 18064999
TI  - [Cross sectional ultrasound of the liver].

PMID- 18065000
TI  - Purification and properties of exo-inulinases from Penicillium janczewskii
      growing on distinct carbon sources.
AB  - Penicillium janczewskii, isolated from the rhizosphere of Vernonia herbacea,
      grows rapidly on media containing either sucrose or inulin, although inulin more
      than sucrose induced the production of inulinases. Three different extracellular
      beta-fructofuranosidases (two inulinases and one invertase) were purified from
      fungal cultures grown on sucrose or inulin, through precipitation with ammonium
      sulfate, and anion-exchange, hydrophobic interaction and gel filtration
      chromatographies. The optimum temperature of the three enzymes was approximately
      60 C, optimum pH 4-5.5 and apparent molecular mass of 80 kDa. K(m) and V(max)
      values determined for invertase on sucrose were respectively 3.7 10(-4) M and 7.9
      10(-2) micromol/min/mL, and on inulin 6.3 10(-2) M and 2.09 10(-2)
      micromol/min/mL. The values of k(m) for the two inulinases were 8.11 10(-4) and
      2.62 10(-3) M, being lower for inulin when compared to those obtained for
      sucrose. The inulinases did not produce oligofructans from inulin, indicating
      they are primarily exoinulinases. The differences found in inulinase induction
      patterns when inulin or sucrose was used seem to be related to modifications on
      the enzyme properties, mainly concerning substrate affinity.

PMID- 18065001
TI  - Protostelids and myxomycetes isolated from aquatic habitats.
AB  - Protostelids and myxomycetes have been isolated from dead plant parts in many
      different habitats, including tropical rain forests and deserts. However
      underwater habitats largely have been overlooked. The purpose of this study was
      to determine whether protostelids do occur in aquatic habitats and to survey the
      myxomycetes associated with these habitats. Protostelids and myxomycetes were
      isolated from substrates collected from just above and just below the surface of
      the water. Several species of both groups were present, and their distributions
      above and below the water were different. It is not surprising that the trophic
      cells of slime molds occur in ponds because they are known to grow in films of
      water. However these findings are significant because this is the first study to
      demonstrate clearly the occurrence of protostelids in underwater environments and
      one of the few surveys of myxomycetes from aquatic systems.

PMID- 18065002
TI  - Mycorrhizal fungi of Vanilla: diversity, specificity and effects on seed
      germination and plant growth.
AB  - Mycorrhizal fungi are essential for the germination of orchid seeds. However, the
      specificity of orchids for their mycorrhizal fungi and the effects of the fungi
      on orchid growth are controversial. Mycorrhizal fungi have been studied in some
      temperate and tropical, epiphytic orchids, but the symbionts of tropical,
      terrestrial orchids are still unknown. Here we study diversity, specificity and
      function of mycorrhizal fungi in Vanilla, a pantropical genus that is both
      terrestrial and epiphytic. Mycorrhizal roots were collected from four Vanilla
      species in Puerto Rico, Costa Rica and Cuba. Cultured and uncultured mycorrhizal
      fungi were identified by sequencing the internal transcribed spacer region of
      nuclear rDNA (nrITS) and part of the mitochondrial ribosomal large subunit
      (mtLSU), and by counting number of nuclei in hyphae. Vanilla spp. were associated
      with a wide range of mycorrhizal fungi: Ceratobasidium, Thanatephorus and
      Tulasnella. Related fungi were found in different species of Vanilla, although at
      different relative frequencies. Ceratobasidium was more common in roots in soil
      and Tulasnella was more common in roots on tree bark, but several clades of fungi
      included strains from both substrates. Relative frequencies of genera of
      mycorrhizal fungi differed significantly between cultured fungi and those
      detected by direct amplification. Ceratobasidium and Tulasnella were tested for
      effects on seed germination of Vanilla and effects on growth of Vanilla and
      Dendrobium plants. We found significant differences among fungi in effects on
      seed germination and plant growth. Effects of mycorrhizal fungi on Vanilla and
      Dendrobium were similar: a clade of Ceratobasidium had a consistently positive
      effect on plant growth and seed germination. This clade has potential use in
      germination and propagation of orchids. Results confirmed that a single orchid
      species can be associated with several mycorrhizal fungi with different
      functional consequences for the plant.

PMID- 18065003
TI  - Invasion of the French paleolithic painted cave of Lascaux by members of the
      Fusarium solani species complex.
AB  - A major fungal invasion was discovered in the prehistoric painted cave of Lascaux
      in France in Sep 2001. At least three species of the Fusarium solani complex were
      isolated and identified with a portion of the translation elongation factor
      1alpha gene (EF-1alpha), a portion of the nuclear large subunit rDNA (LSU) and
      nuclear ribosomal intergenic spacer region (ITS). This study represents the first
      time that Fusarium species have been reported from a cave containing prehistoric
      paintings. Significant interspecific molecular variability was observed,
      suggesting that there might have been repeated introduction of the species,
      possibly carried by water from soils above the cave.

PMID- 18065004
TI  - Distribution and ecology of myxomycetes in the high-elevation oak forests of
      Cerro Bellavista, Costa Rica.
AB  - Myxomycetes associated with a high-elevation (>3000 m) oak forest in the
      Talamanca Range of Costa Rica were studied for 7 mo. Field collections were
      supplemented with collections obtained from moist chamber cultures prepared with
      samples of bark and ground litter of Quercus costaricensis. Various
      microenvironmental parameters including pH, substrate moisture and diameter,
      height above the ground and canopy openness were recorded for each field
      collection, whereas macroenvironmental data for temperature and precipitation
      were obtained from a meteorological station near the study area. Niche breadth
      and niche overlap indices were calculated to assess possible resource
      partitioning by myxomycetes. Thirty-seven species were recorded, including 11 new
      records for Costa Rica, eight for Central America and one for the neotropics.
      Both PCA and NMS multivariate analyses indicated that pH and height above the
      ground explained most of the observed variation, although substrate diameter also
      seemed to be an important factor. Precipitation showed an inverse correlation
      with the number of fruitings, confirming its importance as a macroenvironmental
      factor. Niche overlap values were not higher for closely related species and
      values for niche breadths were similar for most of the more common species,
      suggesting that most members of the assemblage of myxomycetes present in the
      study site are ecological generalists.

PMID- 18065005
TI  - Two new species of Appendiculella (Meliolaceae) from Panama.
AB  - Two new species of Meliolaceae (black mildews) are described based on specimens
      recently collected in western Panama. Appendiculella lozanellae on leaves of
      Lozanella enantiophylla is the first species of Appendiculella known on
      Cannabaceae. Appendiculella chiriquiensis on leaves of Cupania guatemalensis is
      the first record of a species of Appendiculella on Sapindaceae. These species
      differ from known species on their respective host relationships by the presence
      of larviform appendages attached to the perithecia, as well as by characteristics
      of hyphae, appresoria and ascospores. Sequence data of 18S and 28S rDNA are
      published for A. lozanellae, which becomes the third species of Meliolales and
      the first species of the genus Appendiculella for which molecular data are
      available.

PMID- 18065006
TI  - High mobility group (HMG-box) genes in the honeybee fungal pathogen Ascosphaera
      apis.
AB  - The genome of the honeybee fungal pathogen Ascosphaera apis (Maassen) encodes
      three putative high mobility group (HMG-box) transcription factors. The predicted
      proteins (MAT1-2, STE11 and HTF), each of which contain a single strongly
      conserved HMG-box, exhibit high similarity to mating type proteins and STE11-like
      transcription factors previously identified in other ascomycete fungi, some of
      them important plant and human pathogens. In this study we characterized the A.
      apis HMG-box containing genes and analyzed the structure of the mating type locus
      (MAT1-2) and its flanking regions. The MAT1-2 locus contains a single gene
      encoding a protein with an HMG-box. We also have determined the transcriptional
      patterns of all three HMG-box containing genes in both mating type idiomorphs and
      discuss a potential role of these transcription factors in A. apis development
      and reproduction. A multiplex PCR method with primers amplifying mat1-2-1 and
      Ste11 gene fragments is described. This new method allows for identification of a
      single mating type idiomorph and might become an essential tool for applied and
      basic research of chalkbrood disease in honeybees.

PMID- 18065007
TI  - Evidence that a wortmannin-sensitive signal transduction pathway regulates
      aflatoxin biosynthesis.
AB  - A signal transduction pathway involving cAMP and protein kinase A (PKA) regulates
      aflatoxin accumulation and nor-1 and ver-1 (aflatoxin structural genes) promoter
      function in Aspergillus parasiticus by modulating expression of a key
      transcriptional activator, AflR. To understand the function of this pathway in
      greater detail we treated A. parasiticus in culture with wortmannin, a frequently
      used probe of phosphatidyl inositol (PI)-3 kinase activity. A. parasiticus D8D3
      (nor-1::GUS reporter) and I4 (ver-1::GUS reporter) were grown on a defined solid
      growth medium (GMS agar) under aflatoxin-inducing conditions. GMS containing
      wortmannin (1 microM) reduced aflatoxin B1 accumulation up to 15-fold accompanied
      by a similarly large decrease in ver-1 and nor-1 promoter activity. Wortmannin
      inhibited growth (colony diameter) and asexual sporulation but to a much smaller
      extent. Wortmannin treatment increased intracellular cAMP levels up to 25-fold;
      total PKA activity also increased within 10 min of wortmannin exposure. These
      data support a regulatory model in which PI-3 kinase activity modulates
      intracellular cAMP accumulation and PKA activity. This in turn regulates AflR
      expression and activity, aflatoxin gene expression and aflatoxin accumulation.

PMID- 18065008
TI  - Taxonomy of displaced species of Tubaria.
AB  - A taxonomic treatment of vinaceous and reddish species of Tubaria (Agaricales) is
      presented based on morphology and nucleotide sequences. Accessions from western
      North America, Europe, Central America, the Caribbean and Australia are compared.
      Phylogenetic analysis of the 25S rRNA gene and internal transcribed spacer (ITS)
      regions demonstrates that Tubaria is not monophyletic. However the autonomy of
      six brown-spored, saprotrophic species-Naucoria vinicolor, Pholiota serrulata,
      Phaeomarasmius confragosus, Pholiota punicea, Tubaria rufofulva and T. bispora
      sp. nov.-is affirmed. All six species form a strongly supported monophyletic
      group that we label section Confragosae in the genus Tubaria. This section is
      related to T. dispersa, T. albostipitata and numerous representatives of the T.
      furfuracea complex. Tubaria minima is related to other lineages of dark-spored
      Agaricales. Taxonomic descriptions, illustrations and a key to confirmed species
      of section Confragosae are provided. Four new combinations are proposed, and one
      new species, T. bispora, is described as new from Costa Rica and Martinique. A
      lectotype is designated for Pholiota serrulata.

PMID- 18065009
TI  - Symptomatology and morphology of Claviceps cyperi on yellow nut sedge in South
      Africa.
AB  - Symptoms of ergot on yellow nut sedge, germination of sclerotia of the causal
      organism, Claviceps cyperi, and morphology of fresh specimens of the pathogen are
      described for the first time. The initial symptom of infection was a black sooty
      layer on inflorescences of infected plants due to colonization of the ergot
      honeydew by Cladosporium cladosporioides. Sclerotia of C. cyperi started to
      develop in March and April and could be discerned as small protuberances on
      inflorescences in the place of seed. Mature sclerotia were purplish-black. They
      generally remained viable for less than a year and germinated without prior cold
      treatment, although exposure for 21 d to 5 C before incubation significantly
      increased the germination rate. Under moist conditions at 24 C in the laboratory,
      germination commenced within 4-8 wk. Stromata took about 12 d to mature. Mature
      capitula were distinctly lobulate with a perithecium embedded in each lobe and a
      collar-like appendage around the base. Although dimensions of sclerotia, stipes,
      capitula, asci and ascospores were larger than in the original description, the
      general morphology supports treatment of C. cyperi as a distinct species.

PMID- 18065010
TI  - Baudoinia, a new genus to accommodate Torula compniacensis.
AB  - Baudoinia gen. nov. is described to accommodate Torula compniacensis. Reported
      originally from the walls of buildings near brandy maturation warehouses in
      Cognac, France, species of Baudoinia are cosmopolitan colonists of exposed
      surfaces subjected to large diurnal temperature shifts, episodic high relative
      humidity and wetting, and ambient airborne ethanol. Morphologically B.
      compniacensis resembles some anamorphic Mycosphaerellaceae in possessing dark
      brown, nonseptate or uniseptate conidia with coarsely roughened walls that are
      borne acropetally in unbranched chains and released by schizolytic dehiscence.
      Analysis of partial nuclear rDNA SSU sequences positions B. compniacensis in the
      order Capnodiales and reveals that it is most closely related to the
      microcolonial genus Friedmanniomyces. Heat resistance is induced by brief
      sublethal temperature exposure.

PMID- 18065011
TI  - Description and culture of a new succulenticolous Didymium (Myxomycetes).
AB  - A new succulenticolous Myxomycete species, Didymium wildpretii, found on decaying
      remains of various species of cacti, is described from two arid zones of the
      world. This species was collected from central Mexico, at the southern limit of
      the Chihuahuan Desert, and from the Canary Islands (Spain). The new species has
      small, pale yellow sporocarps, 0.1-0.7 mm high, that are sessile or have short,
      orange-yellow, calcareous stalks and small, uniformly warted spores. The
      stability of the taxonomic characters of the species was confirmed with both
      moist chamber cultures and spore-to-spore culture on agar. Life cycle events are
      described from germination to sporulation. Myxomycete specimens were examined
      with scanning electron microscopy and light microscopy, and micrographs of
      relevant morphological details are included.

PMID- 18065013
TI  - Tylopilus orsonianus sp. nov. and Tylopilus eximius from Guyana.
AB  - Tylopilus orsonianus sp. nov. and Tylopilus eximius (Boletaceae, Basidiomycota)
      are described for the first time from the Pakaraima Mountains of Guyana. Both
      boletes occur in forests dominated by ectomycorrhizal trees in the genus Dicymbe
      (Caesalpiniaceae). A key to Tylopilus species distinguishes those known to occur
      in Guyana.

PMID- 18065012
TI  - Theissenia rogersii sp. nov. and phylogenetic position of Theissenia.
AB  - Theissenia rogersii deviates from known Theissenia species primarily in having
      large ascospores with a thick wall layer and a unique configuration of two
      stromatal tissue types, one carbonaceous and the other fibrous. The carbonaceous
      tissue forms palisades on and beneath the perithecial layer as well as encasing
      individual perithecia, whereas the fibrous tissue fills the spaces between
      columns of the palisades as well as between encased perithecia. Phylogenetic
      analyses based on DNA sequences of beta-tubulin and alpha-actin genes placed
      Theissenia in the subfamily Hypoxyloideae among the genera that are characterized
      by having bipartite stromata (i.e. with the stromata differentiated into an outer
      dehiscing layer and an inner perithecium-bearing layer).

PMID- 18065015
TI  - Modern dressings: must do better.

PMID- 18065014
TI  - Heteroconium and Pirozynskiella n. gen., with comments on conidium
      transseptation.
AB  - Heteroconium citharexyli, the type species of this genus, is illustrated and
      redescribed as a sooty mold bearing acropetal chains of conidia showing a
      basifugal sequence of septation. Heteroconium neriifoliae, H. glutinosa and the
      Heteroconium synanamorph of Antennulariella concinna are congeneric. The latter
      species is neotypified, illustrated and described. Pirozynskiella new genus,
      typified by P. solaninum comb. nov. (-Helminthosporium solaninum), differs from
      Heteroconium in having an obligate association with asterinaceous fungi and in
      the centrifugal sequence of conidium transseptation after the initial median
      septum. Pirozynskiella costaricensis comb. nov. (-Dendryphion costaricensis) is
      illustrated and described. Heteroconium tetracoilum and H. chaetospira are
      fungicoles of wood and bark; the former has basifugal conidium septation and the
      latter has a centrifugal sequence. The two latter species can be excluded from
      the Heteroconium. Basifugal and centrifugal septation of conidia is discussed
      with reference to several sooty molds, to some foliicolous anamorphs with
      subcuticular hyphae (Heterosporiopsis) and to some wood and bark hyphomycetes
      (Septonema, Taeniolella). Ten other species included in Heteroconium are known to
      me only from their original descriptions; only one (H. asiaticum) is probably a
      sooty mold.

PMID- 18065016
TI  - A point prevalence survey of wounds in north-east England.
AB  - OBJECTIVE: To review current wound-care practice and the standard of wound care
      in Hull and East Yorkshire; obtain information on prevalence, treatment and
      outcomes; provide a basis for estimating the extent of the problem, treatment
      modalities used, service provision and future needs; highlight areas of care in
      need of improvement; highlight areas with excellent wound practices and gain
      information for future research projects within the population of the region.
      METHOD: Point prevalence interface audit of community and acute trusts. RESULTS:
      The cumulative wound prevalence for the region was 12%. Community nurses were
      involved in caring for 70.1% of patients with wounds, with 52.7% of wounds being
      treated in the patient's home. The largest proportion of wounds were surgical
      wounds (n=699, 41.5%), followed by leg and foot ulcers (n=629, 37.3%) and
      pressure ulcers (n=294, 17.4%). Diabetes and cancer were related to 15.1% and
      9.7% of the wounds respectively. 41.9% of the wounds were on the lower leg. The
      primary and secondary dressings used the most were low/non-adherent dressings at
      25.9% and 27.3% respectively.Almost half of the patients with a venous leg ulcer
      (46%) did not receive multilayer compression and 7% of patients with an arterial
      ulcer did; 23.6% of the leg and foot wounds were not assessed with a Doppler.
      CONCLUSION: Wounds represent a significant cause of morbidity in the general
      population.A systematic focus is necessary on effective and timely diagnosis, on
      ensuring treatment is appropriate to the cause and condition of the wound and on
      active measures to prevent complications.A number of initiatives have commenced
      in order to provide a effective and efficient wound care.

PMID- 18065017
TI  - A collaborative approach to education provision will help save our specialism.
AB  - In the UK, education on tissue viability is delivered on an ad hoc basis, with a
      wide range of providers and educational materials. Clinicians and academics need
      to work together to ensure common goals that will help standardise such
      provision.

PMID- 18065018
TI  - Use of ultrasound to characterise the fluid-handling characteristics of four foam
      dressings.
AB  - OBJECTIVE: To observe and measure the process of hydration and dehydration in
      four commonly used adhesive foam dressings using high frequency ultrasound.
      METHOD: High frequency ultrasound (20MHz) with an axial resolution of 60 microm
      was used to image the inside of the wound dressings under investigation and
      thereby assess their level of hydration. This allowed the uptake of a bolus of
      fluid into the dressing via absorption and the subsequent loss of fluid via
      evaporation to be both observed and measured. Four dressings were
      assessed:ActivHeal Foam Island (10 x 10cm), Allevyn Adhesive (10 x 10 cm),
      Biatain Adhesive (12 x 12cm), and Mepilex Border (10 x 10 cm). RESULTS: Part I
      showed that Allevyn hydrated most rapidly followed byActivHeal, Biatain and
      Mepilex. Part 2 indicated that Allevyn dehydrated most rapidly followed by
      Mepilex,ActivHeal and Biatain. CONCLUSION: High frequency ultrasound proved to be
      an effective tool in assessing the fluid handling properties of wound dressings.
      Of the dressings tested Allevyn demonstrated the best fluid handling properties
      in terms of how rapidly it could hydrate and dehydrate.

PMID- 18065019
TI  - Split-thickness skin graft donor sites: a comparative study of two absorbent
      dressings.
AB  - OBJECTIVE: To identify the optimal dressing for split-thickness skin graft (SSG)
      donor sites. METHOD: This prospective randomised controlled trial compared two
      dressings - a new absorbent form of a polyurethane film dressing (Tegaderm
      Absorbent, 3M) and our standard alginate dressing (Kaltostat, ConvaTec) - on SSG
      donor sites in 40 patients. Primary outcome measures were: reduced time to full
      healing; reduced postoperative pain; reduced leakage rates from the dressing.
      Secondary outcome measures related to acceptability of the dressings to the
      patient. RESULTS: On removal of the dressings at the first assessment, 79% of the
      Tegaderm Absorbent donor sites had healed completely, compared with 16% of the
      Kaltostat ones (p<0.001).A significantly greater median area had healed with
      Tegaderm Absorbent (100%), when compared with Kaltostat (89%) (p<0.001). Mean
      time to complete healing was also significantly faster for Tegaderm Absorbent
      than Kaltostat (14 versus 21 days) (p<0.001). Significantly fewer subjects
      experienced postoperative pain with Tegaderm Absorbent on both day 1 (21% versus
      67%, p=0.006, NNT=3) and day 2 (17% versus 75%, p<0.001, NNT=2). Leakage rates
      reduced by 48% with Tegaderm Absorbent, with no leakage in the smaller donor
      sites. Tegaderm Absorbent was significantly easier to apply than Kaltostat (89%
      versus 27% found it'very easy') as was ease of removal (84% versus 11% found
      it'very easy') (p<0.0001). Patients found Tegaderm Absorbent dressings
      significantly more convenient to manage and bathe with. At one month post
      surgery, Vancouver scar scores showed thatTegaderm Absorbent donor sites were
      less red, flatter, softer and less itchy. CONCLUSION: Tegaderm Absorbent provides
      a significant improvement in terms of donor-site pain, healing and ease of
      management.

PMID- 18065020
TI  - Use of Dermabond tissue adhesive in hand surgery.
AB  - OBJECTIVE: To assess the efficacy and safety of a tissue adhesive for wound
      closure in elective hand surgery. METHOD: A prospective observational study of
      the use of Dermabond for wound closure was undertaken. The cohort consisted of a
      consecutive case series of 105 patients and 114 surgical wounds. Surgeon and
      patient assessment was undertaken at a mean of 20 days (10 to 56 days)
      postoperatively. RESULTS: Wound complication rate was low (one adverse event) and
      all patients were satisfied (46%) or very satisfied (54%) with wound healing and
      cosmesis. CONCLUSION: Dermabond use in hand surgery is safe and well tolerated by
      patients. Routine postoperative wound review in these patients may not be needed
      thereby saving time and resources.

PMID- 18065021
TI  - Evaluation of two absorbent silver dressings in a porcine partial-thickness
      excisional wound model.
AB  - OBJECTIVE: To investigate and compare the performance of two widely used silver
      containing, fibre-based dressings (Silvercel and Aquacel Ag) in terms of exudate
      management, wound-site adherence, dressing integrity, retention of dressing
      debris within wounds, frequency of debris-associated foreign body reactions and
      the impact of both debris and tissue reactions on wound-tissue integrity. METHOD:
      The dressings were evaluated in a porcine partial-thickness exudating wound model
      (an in vivo model of moderate to high exudation up to post-wounding day 4, and
      low exudation from days 4 to 7). Dressing performance was assessed using a panel
      of semi-quantitative scales.Wound-exudate retention, dressing structure following
      exposure to exudate, and adherence to wound tissues were compared
      macroscopically; the extent of trapped dressing debris, any ensuing tissue
      reactions and the level of resulting tissue disruption were compared
      histologically. RESULTS: Silvercel was found to be significantly more effective
      in terms of wound exudate management than Aquacel Ag. On exposure to high levels
      of wound exudate, Silvercel retained its shape and mechanical strength, and
      remained at the site of application. In contrast, Aquacel Ag formed a fluid (semi
      fibrous) gel, with minimal mechanical integrity and variable retention at the
      wound site. Silvercel was significantly more adherent to wound tissues than
      Aquacel Ag, but the level of trapped dressing debris, the frequency of ensuing
      foreign body reactions and the level of consequent wound-tissue disruption was
      lower, although not statistically, in the Silvercel-treated wounds. CONCLUSION:
      These results suggest that the potential adverse clinical consequences of
      unmanaged wound exudate may be less likely in Silvercel than Aquacel Ag-treated
      wounds. In addition, the adverse effects of dressing adherence may be less likely
      in Aquacel Ag-treated wounds, although such benefits may be negated by the
      potentially deleterious effects of elevated dressing debris deposition. In view
      of these findings, further development of absorbent fibre-based dressings should
      be directed at maximising exudate management, minimising dressing adherence and
      preventing dressing-debris entrapment.

PMID- 18065022
TI  - Extracellular matrix prevents split-skin grafting in selected cases.
AB  - Surgeons at a Dutch wound clinic close open wounds with split-skin grafts.
      Concerns about the risk of postoperative complications in some patients led them
      to find an alternative option. Use of an extracellular matrix dressing was
      effective.

PMID- 18065023
TI  - A personal leadership journey.
AB  - The author discusses the challenges she has faced during her tenure as chair of
      the School of Nursing at Old Dominion University and how participation in Project
      LEAD has had a positive impact on her development as a program director. She
      describes her leadership journey as head of the School of Nursing. The author
      also discusses the value of role models and mentoring during the Project LEAD
      experience. Benner's model of development is used by the author as a framework to
      chronicle her leadership progression, and there is an in-depth discussion of the
      five leadership stages: novice, advanced beginner, competent, proficient, and
      expert. The author demonstrates how she has progressed through the stages of
      Benner's model of development and shares how her patterns of thinking and
      behavior have progressed accordingly.

PMID- 18065024
TI  - My continuing journey through project LEAD (Leadership Enhancement and
      Development).
AB  - The author discusses how her experiences at Project LEAD have improved her
      ability to accept new job responsibilities and be an effective administrator. The
      LEAD model allowed her to mature in confidence and successfully complete projects
      in LEAD and in her competitive work environment. During LEAD, the fellows were
      given mentors, and the author's assigned mentor was instrumental to her success.
      She has realized that those scholars who shared their expertise with LEAD fellows
      also acted as mentors and brought invaluable tenets of leadership. These scholars
      have lived by these tenets and are role models to be emulated. The LEAD model
      provided her with new skill sets and new ideals that will be beneficial to her
      for decades to come.

PMID- 18065025
TI  - My continuing journey of leadership: application of lessons learned.
AB  - The author is the dean of a School of Nursing and has had to make major
      leadership decisions throughout her career during her tenure as an administrator.
      In one of the schools in which she has served, comprehensive examinations were an
      issue for students, faculty, and administrators. When comprehensive examinations
      were failed, students were dismissed in accordance with school policy. In several
      situations regarding appeals of the dismissals, students were given the
      opportunity to participate in the academic review process. In one instance, the
      students wrote a letter to the author who relied on the teachings of Project LEAD
      to evaluate the situation objectively. Based on her evaluation, the author
      decided the students had valid criticisms. The decision to allow the students to
      remain enrolled was contrary to the culture of the school, which blamed the
      students for failure. The author decided to use lessons from Project LEAD to
      guide her in making a decision.

PMID- 18065026
TI  - Leadership--the journey continues.
AB  - A nurse administrator describes how Project LEAD helped her to assume new
      leadership responsibilities following the destruction of the campus during
      hurricane Katrina. Due to the disaster the school's traditional structure
      disappeared and many questioned whether the university could continue to
      function. The university had to create a new organizational structure in response
      to the crisis, and administrators had to assume new roles in addition to their
      traditional roles in order to ensure the university's survival. The four
      organizational frames by Bolman and Deal and the teachings of Dr. Height on
      leadership are discussed extensively, and the author illustrates how Project LEAD
      served as a guide for the administrator as she assumed new responsibilities
      during this unprecedented crisis.

PMID- 18065027
TI  - Discharging responsibilities.

PMID- 18065028
TI  - Just another dignity report.

PMID- 18065029
TI  - When living becomes difficult.

PMID- 18065030
TI  - Indignity in care: are you responsible?

PMID- 18065031
TI  - Reversal of fortunes.

PMID- 18065032
TI  - First-hand experience of taking action against elder abuse.

PMID- 18065033
TI  - Dignity is a human rights issue and should be the underlying principle for
      service delivery.

PMID- 18065034
TI  - No particular place to go.

PMID- 18065035
TI  - Keeping the pressure up.

PMID- 18065036
TI  - A design for independence.

PMID- 18065037
TI  - Preparing undergraduates for practice placements in gerontological nursing.
AB  - An innovative approach was employed to help undergraduate student nurses prepare
      for a practice placement working with older people. The method involved the use
      of life histories as a means of gaining insight into the unique experiences of
      indivduals and how those experiences help shape the person. This narrative
      approach is valuable in assessing need and in ensuring that the care provided is
      of a high standard. Research suggests that it can also help boost the quality of
      life of older people and the self-esteem of the staff involved. To contextualise
      this subject, a brief overview of the relevant demographics of this client group
      is offered to help set the scene of the care environments in which the students
      were to be be placed.

PMID- 18065039
TI  - Admission of error?

PMID- 18065038
TI  - Community matrons: documenting the specialist contribution of the role (Part 6).
AB  - This is the final article of a series of six which draw on the contentof some
      masterclasses organised and funded by the Department of Health for community
      matrons during summer 2006. It highlights the two-old importance of evaluation in
      promoting and supporting successful embedding of the role. Firstly, evaluation
      approaches that post-holders and their managers might use to demonstrate the
      value of the community matron role in order to ensure its propagation are
      suggested. Secondly, insights are gleaned from existing evaluations of new
      nursing roles to suggest factors that are likely to encourage or hinder the
      successful establishment of the community matron role.

PMID- 18065040
TI  - A different kind of care.

PMID- 18065041
TI  - Elbow injuries.

PMID- 18065042
TI  - Lisfranc fracture.
AB  - Nurses working in emergency care often have to manage patients with
      undifferentiated and previously undiagnosed conditions. This month, Emergency
      Nurse continues to look at how emergency nurses across the U.K. have tackled
      them.

PMID- 18065043
TI  - High-pressure injection injuries.

PMID- 18065044
TI  - The properties of aminophylline.

PMID- 18065046
TI  - Media reports of declining standards in nursing are not always inaccurate.

PMID- 18065045
TI  - Trauma training: a literature review.

PMID- 18065047
TI  - [Giant cell arteritis].

PMID- 18065048
TI  - [Swimming for 12 hours leads to no reduction of adipose subcutaneous tissue--a
      case study].
AB  - In a 12-hour swimming event, an athlete with constant body weight lost 1.1 kg of
      muscle mass and 21 of total body fluids whereas fat mass remained stable. Based
      both on the urine's specific gravity and haematological parameters, the athlete
      did not suffer from dehydration. We assume that loss of skeletal muscle mass
      occurred due to degradation of intramyocellular lipids and muscle glycogen. In
      order to confirm these results obtained in a case study regarding the decrease of
      skeletal muscle mass with stable fat mass during prolonged swimming exercise, a
      larger number of athletes would have to be analyzed.

PMID- 18065049
TI  - [Pneumatosis cystoides intestinalis: a rare illness in adults].
AB  - Pneumatosis cystoides intestinalis (PCI) is a rare illness in adults with gas
      filled blebs found in the submucosa or subserosa of the bowel wall. The main
      localization is the terminal ileum although all parts of the intestine can be
      affected. Clinical symptoms can vary from aqueous-slimy, bloody diarrhea to
      constipation and/or vague abdominal pain. Patients can also be completely
      asymptomatic. In symptomatic patients the therapy of PI is based on the assumed
      pathogenesis, so that a combined treatment of metronidazole 1500 mg daily during
      a period of 6-8 weeks additionally and oxygen application (PaO2 of 200-350 mmHg)
      for 7 days is suggested. In addition, elemental diets are recommended.
      Complications are indicated in the literature with 3%. In particular mechanical
      ileus, invagination and perforation as well as substantial intestinal bleeding up
      to the volvolus lead to further diagnostic and therapeutic steps. A surgical
      intervention is reserved for rare cases.

PMID- 18065050
TI  - [A rare cause of cervical adenopathy].
AB  - We report the case of a young woman, who presented a sus-clavicular adenopathy
      with fever and inflammatory syndrome. A cervico-thoracic scan reveals sus
      clavicular and hilar adenopathies with central necrosis. Laboratory studies,
      including blood culture and viral serologies were negative, and excluded an
      infectious aetiology. Clinical features and anti-nuclear antibody tests were not
      compatible with an inflammatory autoimmune disease. Bone marrow examination and
      lymph node histology didn't show any malignant cell. Histology analysis of the
      lymph node showed a typical aspect of histiocytic necrotizing lymphadenitis. This
      is compatible with the diagnosis of Kikuchi's disease.

PMID- 18065051
TI  - [Bilateral axillary nodes. 30-year-old patient, housewife].
AB  - A 20-year old patient who had been adequately treated for lymph node tuberculosis
      14 years ago presented 1 week after giving birth to a healthy daughter. She
      complained about painful lumps in both axillae. During pregnancy the patient
      suffered from hyperemesis gravidarum, lost 6 kg of weight, and had night sweats.
      During the last three months of her pregnancy she had a deep vein thrombosis in
      her right lower leg. The clinical examination showed soft axillary lumps up to 3
      cm. The lab showed the following pathological findings: blood sedimentation rate
      51 mm/h, CRP 44.8 mg/l, LDH 221 U/l and INR 1.3 (indicating insufficient
      anticoagulation with phenprocoumon). The chest x-ray showed no infiltrate or
      indications of a past tuberculosis. A fine needle aspiration cytology was
      performed on an accessible node. Gram stain, Ziehl Neelsen stain, as well as the
      bacteriological cultures were all negative. An ultrasound examination of the
      axilla showed a thickened subcutis without a mass. Cytology showed lobular
      epithelium, consistent wih ductal mamma epithelium without atypical cells. The
      diagnosis of an accessory mamma tissue in both axillae was made. During the
      course of the following weeks the glands decreased in size and the patient was
      free of symptoms.

PMID- 18065052
TI  - A world view of nursing education and practice.

PMID- 18065053
TI  - Chapter 2. Military nursing 1948-1954.

PMID- 18065054
TI  - Greener practice settings make healthier work environments.

PMID- 18065055
TI  - The nursing faculty crisis.

PMID- 18065056
TI  - National differences in intelligence and population rates of suicidal ideation,
      suicide plans, and attempted suicide.
AB  - Population rates of suicidal ideation, suicide plans or attempted suicide from
      three independent multinational epidemiological surveys (the WHO/EURO and WHO
      SUPRE-MISS studies and a third one) were not significantly associated with
      national IQ figures. This result conflicts with previous evidence from cross
      national studies (by Lester and by Voracek) of a positive ecological correlation
      between level of national intelligence and rates of completed suicide. Across
      nations, the indicators for the prevalence of suicidal behavior also lacked close
      correspondence with suicide rates, which may be due to the higher unreliability
      of assessing covert suicidal behavior (suicide ideas, thoughts, plans, and, to a
      lesser extent, also suicide attempts) as compared to suicidal behavior that is
      indisputably overt (completed suicide). Several alternative explanations for the
      current nil findings are also discussed.

PMID- 18065057
TI  - Enabling two adolescents with multiple disabilities to choose among environmental
      stimuli through different procedural and technological approaches.
AB  - Two single-case studies were carried out using different procedural and
      technological approaches to enable two adolescents with multiple disabilities to
      choose among environmental stimuli. Study I focused on replicating a recently
      developed procedure, which relied on samples of the auditory stimuli available as
      cues for choice responses. Study II assessed a new procedural and technical setup
      relying on the use of pictorial representations of the stimuli available as cues
      for choice responses. The auditory samples and the pictorial representations were
      presented through computer systems. The participants' choice responses relied on
      microswitches connected to the computer systems. The data of Study I fully
      supported previous findings with the same procedural approach. The participant
      learned to choose preferred stimuli and bypass nonpreferred ones. The data of
      Study II showed that the participant learned to concentrate his choice. responses
      on a few stimuli, suggesting that these stimuli were actually preferred and that
      responding was purposeful. Implications of the results were discussed.

PMID- 18065058
TI  - Undergraduate education majors' knowledge about suicide.
AB  - Undergraduate education majors' knowledge about suicide was evaluated to identify
      what training they may need about suicide prevention and to explore the
      hypothesis that individuals previously exposed to suicide in their social context
      may hold higher suicide-related knowledge than those without. 71 college students
      completed the 50-item Expanded Revised Facts on Suicide Quiz to examine their
      knowledge about suicide. While overall knowledge was low for general information
      and for specific items concerning suicide among youth and elderly persons,
      knowledge was high on several items important for suicide prevention work. Higher
      suicide-related knowledge was found for knowing a suicide attempter, providing
      partial support for the hypothesis that personal experience with suicidal people
      may correspond with greater knowledge about suicide.

PMID- 18065059
TI  - Immediate effect of two yoga-based relaxation techniques on performance in a
      letter-cancellation task.
AB  - The performance in a six-letter cancellation task was assessed with 69 male
      volunteers, ages 18 to 48 years, immediately before and after two yoga-based
      relaxation techniques and a control session of equal duration. The techniques
      were Cyclic Meditation and Supine Rest. Cyclic Meditation consists of alternating
      cycles of yoga postures and supine rest. After both practices, the net scores
      were significantly higher, although the magnitude of change was more after Cyclic
      Meditation than after Supine Rest (24.9% versus 13.6%). There was reduction in
      scores for wrong cancellations after Cyclic Meditation and not after Supine Rest.
      The control group showed no change. The results suggest that Cyclic Meditation
      brings about a greater improvement in performance in this task, which requires
      selective attention, concentration, visual scanning abilities, and a repetitive
      motor response.

PMID- 18065060
TI  - Relations of perceived motivational climate and feelings of belonging in physical
      education in urban schools.
AB  - The current pilot study examined the relationship between feelings of belonging
      and perceptions of motivational climate in physical education classes among 87
      African-American, inner-city high school students (41 boys, 46 girls).
      Motivational climate was assessed by the Perceived Motivational Climate
      Questionnaire and feelings of belonging were assessed by the Belonging Scale.
      Contrary to the hypothesis, scores for both the task- and ego-involved subscales
      of the Perceived Motivational Climate Questionnaire had moderate positive
      correlations with scores on the Belonging Scale, indicating the relationship
      between these specific motivational climates and social-emotional outcomes in
      physical education is not clear and direct. Further research is warranted to
      assess these findings and to identify what experiences and instructional
      strategies are most effective in promoting social-emotional outcomes in physical
      education in urban schools.

PMID- 18065061
TI  - Evidence for a positive ecological correlation of regional intelligence and
      suicide mortality in the United States during the early 20th century.
AB  - Several contemporary cross-national and intranational geographic studies have
      reported positive ecological (group-level) associations of intelligence and
      suicide mortality. These findings are consistent with facts from suicide research
      and with an evolutionary view of suicidal behavior. The present research extended
      these accounts cross-temporally. Analysis of E. L. Thorndike's state-level
      personal quality scores and standardized birth rates of eminent persons, taken as
      proxy variables for regional intelligence, along with historical state suicide
      rates (1913-1924 and 1928-1932) showed that intelligence and suicide mortality
      across the U.S.A. were already clearly positively related during the early 20th
      century, suggesting time stability of the effect. Within the U.S.A., the effect
      is possibly due to state differences in the ethnic composition, which correspond
      to both suicide rates and intelligence proxies. It is argued that the most
      parsimonious interpretation of these ecological findings remains that they indeed
      reflect individual-level effects, that a positive link between intelligence and
      suicide is entirely compatible with positive overall links between intelligence
      and health and longevity, and that the ultimate explanative background for the
      positive link between intelligence and suicide may be provided through the
      framework of Rushton's differential K theory.

PMID- 18065062
TI  - Sex differences in preferences for coffee sweetness among Japanese students.
AB  - The purpose of the present study was to examine sex differences in preferences
      for coffee sweetness. The participants were 59 Japanese undergraduate students.
      Men preferred sweeter coffee than women, while both men and women showed almost
      the same preference for acidic beverage sweetness. The sex difference in
      preferences for coffee sweetness may be related to coffee-drinking habits.

PMID- 18065063
TI  - Processing of segmental and tonal information of Chinese syllables.
AB  - In the phonological system of Chinese, a unique Chinese syllable usually
      comprises three components: onset, rime, and tone. The present study, with 30
      participants, examined how native Chinese listeners process these subsyllabic
      components of Chinese by a syllable comparison task. Analysis showed that the
      cognitive processing of these subsyllabic components was different after the
      encoding process of the Chinese syllable. These results are discussed in light of
      the perception of Chinese language.

PMID- 18065064
TI  - Towards a psychology of photography: dimensions underlying aesthetic appeal of
      photographs.
AB  - With the aim to contribute to the development of a psychology of photography,
      this study examined what attributes are the major determinants of aesthetic
      appeal of photographs. Two interlinked experiments were conducted with 564
      photographs having a wide range of motifs. Exp. 1 consisted of sorting by
      aesthetic appeal and adjective generation. In Exp. 2, attribute scaling was
      collected. Multidimensional scaling analysis of the photographs yielded three
      dimensions identified with the aid of attribute scales combined with measures of
      the manifest content of the photographs. The three dimensions were Hedonic Tone
      Familiarity, Absence of color, and Expressiveness-Dynamics. The present results
      suggested that participants' familiarity with the photographs, the types of
      photographs (Color or Black & White), and the photographs' dynamics all affected
      participants' judgments of aesthetic appeal. Hedonic Tone and Expressiveness
      apparently mediated the participants' judgments.

PMID- 18065065
TI  - Testing assumptions of deliberate practice theory relevance, effort, and inherent
      enjoyment of practice with a novel task: study II.
AB  - This study examined three assumptions of the theory of deliberate practice: that
      deliberate practice is perceived as relevant for improving performance and that
      it requires effort, but that it is not perceived as being inherently enjoyable.
      Of particular interest was how these perceptions change as practice difficulty
      changes. 30 college undergraduates practiced two different maze memorization and
      replication tasks and rated the practice relevance for improving performance on
      the task, the practice effort, and the inherent enjoyment of practice. The
      findings for each of the assumptions were consistent with those suggested by the
      theory and also showed that these perceptions are subject to the current
      performance on an activity and the difficulty of the practice.

PMID- 18065066
TI  - Interactions of speech and manual movement in a syncopated task.
AB  - The present study examined interactions of speech production and finger-tapping
      movement, using a syncopated motor task with two movements in 10 male right
      handed undergraduate students (M age = 21.0 yr.; SD = 1.4). On the syncopated
      task, participants were required to produce one movement exactly midway between
      two other movements (target interresponse interval: 250 msec.). They were divided
      into two groups, the tap-preceding group and speech-preceding group. The author
      observed that the right hand showed a more variable peak force and intertap
      interval than the left hand in the speech-preceding group, indicating an
      asymmetrical interference of two movements. On the other hand, the mean
      differences between onsets of speech and tapping movement were shorter than 250
      msec. over all conditions (the shortest mean difference was 50 msec.), suggesting
      a mutual entrainment of two movements. An asymmetry of entrainment was observed
      in the speech-preceding group, in which speech production was more strongly
      entrained with movements of the right hand than with those of the left hand.

PMID- 18065067
TI  - Imagery intervention in open and closed tennis motor skill performance.
AB  - To assess use of imagery intervention in performance of two tennis motor skills
      the quasi-experimental design included a pre- and posttest and a control group.
      The tennis service shot and service receiving skill were selected as
      representative of open and closed skills, respectively. 48 subjects, male tennis
      players, whose ages ranged from 16 to 18 yr. (M = 17.2), were divided into two
      groups: (1) Technical practice only which was used as control group and (2)
      Imagery group who received both imagery and technical practice. Analysis of
      covariance showed a significant main effect for the imagery intervention on the
      closed skill (p = .002). Findings suggest that imaging a positive outcome may be
      more powerful in improving performance of closed skill movements than of open
      skill movements.

PMID- 18065068
TI  - Development of a Japanese version of the emotional skills and competence
      questionnaire.
AB  - The present study described development of a Japanese version of the Emotional
      Skills and Competence Questionnaire and examined the relations of scores with
      those on Big Five scales of personality and self-esteem scales. The participants
      were 615 undergraduates. Factor analysis led to the shortened version of 24 items
      in three subscales. Although Cronbach alphas were low for the subscale, Manage
      and Regulate Emotion, values were satisfactory for the other two subscales,
      Express and Label Emotion and Perceive and Understand Emotion. Total scores of
      this version were positively correlated with score for self-esteem, Extraversion,
      and Openness but negatively correlated with scores on Neuroticism. This shorter
      Japanese versions shows suitable internal consistency and content validity, but
      other reliabilities and validities must be examined precisely.

PMID- 18065069
TI  - Emotion recognition and expression in young obese participants: preliminary
      study.
AB  - This study of the presence of alexithymic characteristics in obese adolescents
      and preadolescents tested the hypothesis of whether they showed impaired
      recognition and expression of emotion. The sample included 30 obese young
      participants and a control group of 30 participants of normal weight for their
      ages. Stimuli, 42 faces representing seven emotional expressions, were shown to
      participants who identified the emotion expressed in the face. The Level of
      Emotional Awareness Scale was adapted for children to evaluate their ability to
      describe their emotions. Young obese participants had significantly lower scores
      than control participants, but no differences were found in recognition of
      emotion. The lack of words to describe emotions might suggest a greater
      prevalence of alexithymic characteristics in the obese participants, but the
      hypothesis of a general deficit in the processing of emotional experiences was
      not supported.

PMID- 18065070
TI  - Primacy and recency effects in immediate free recall of sequences of spatial
      positions.
AB  - This study evaluated the serial position curve based on free recall of spatial
      position sequences. To evaluate the memory processes underlying spatial recall,
      some manipulations were introduced by varying the length of spatial sequences
      (Exp. 1) and modifying the presentation rate of individual positions (Exp. 2). A
      primacy effect emerged for all sequence lengths, while a recency effect was
      evident only in the longer sequences. Moreover, slowing the presentation rate
      increased the magnitude of the primacy effect and abolished the recency effect.
      The main novelty of the present results is represented by the finding that better
      recall of early items in a sequence of spatial positions does not depend on the
      task requirement of an ordered recall but it can also be observed in a free
      recall paradigm.

PMID- 18065071
TI  - Separate movement planning and spatial assimilation effects in sequential
      bimanual aiming movements.
AB  - This study extended earlier work by showing spatial assimilations in sequential
      bimanual aiming movements when the participant preplanned only the first movement
      of a two-movement sequence. Right-handed participants (n=20, aged 18 to 22 years)
      made rapid lever reversals of 20 degrees and 60 degrees singly and sequentially
      with an intermovement interval of 2.5 sec. Following blocked single practice of
      both movements in each hand (15 trials each), two sets of 30 sequential practice
      trials were completed. The sequences began with either the long or the short
      movement and the participant always knew the goal of the first movement. During
      the intermovement interval, the experimenter gave instructions to complete the
      sequence with a short movement, a long movement, or no movement in a random
      order. Compared to the single trials, both movements in the sequence overshot the
      short-distance and undershot the long-distance goal. Spatial errors increased
      when a change in the movement goal was required for the second movement in the
      sequence. The experiment demonstrated that separate planning of sequential aiming
      movements can reduce spatial assimilation effects, but interference due to
      practice organization and switching the task's goal must also be overcome in
      order to produce accurate aiming movements.

PMID- 18065072
TI  - Hands-free versus hand-held cell phone conversation on a braking response by
      young drivers.
AB  - As some states allow motorists to use hands-free cell phones only while driving,
      this study was done to examine some braking responses to see if conversing on
      these two types of cell phones affects quick responding. College-age drivers
      (n=25) completed reaction time trials in go/no-go situations under three
      conditions: control (no cell phone or conversation), and conversing on hands-free
      and hand-held cell phones. Their task involved moving the right foot from one
      pedal to another as quickly as possible in response to a visual signal in a lab
      setting. Significantly slower reaction times, movement times, and total response
      times were found for both cell phone conditions than for the control but no
      differences between hands-free and hand-held phone conditions. These findings
      provide additional support that talking on cell phones, regardless if it is hands
      free or hand-held, reduces speed of information processing.

PMID- 18065073
TI  - Short-duration, high-intensity exercise and performance of a sports-specific
      skill: a preliminary study.
AB  - The purpose of this study was to examine the effect of one bout and three
      intermittent bouts of short-duration, high-intensity running on the performance
      of a sports-specific psychomotor skill. Participants (N=13) were male soccer
      players (M age 20.5 yr., SD=2.0) who had been playing semi-professionally for
      M=2.1 years, SD=1.11 and trained twice a week. They undertook a soccer-passing
      test in three conditions: following rest, following a 100-m sprint and following
      3 x 100-m sprints, with 30-sec. rest intervals between sprints. Passing accuracy
      showed a significant linear deterioration, while number of passes showed a
      significant quadratic effect. Low to moderate linear regression correlations were
      found between posttest heart rate and absolute and variable errors on the test.
      It was concluded that short-duration, high-intensity exercise has a negative
      effect on accuracy in a sports-specific task that requires both perceptual
      judgment and motor control.

PMID- 18065074
TI  - A Japanese treatment used in major depressive disorder in adolescence.
AB  - The purpose of the present report is to study the efficacy of a Dohsahou, a
      Japanese Psychorehabilitation method, in a treatment of major depression in three
      men (M age = 20 yr.), selected randomly for treatment. Initially, participants'
      baseline condition was assessed with the Beck Depression Inventory, Hamilton
      Rating Scale for Depression, and the Family Assessment of Depression
      Questionnaire. Each subject had 12 sessions of 45 min. training over 4 wk.
      Postassessment and follow-up assessment were done. Findings for pre- and
      posttreatment test data indicated depression was reduced, being mainly evident in
      cognitive, somatic, and affective symptoms related to lower depression.

PMID- 18065075
TI  - Relation of fatigue with alexithymia and depression in psychiatric outpatients.
AB  - The complaint of fatigue is common in community, primary care, and psychiatric
      settings. Fatigue is often associated with depression and psychosocial stress.
      This report investigated the role of alexithymia and depression in fatigue as
      reported in a sample of 151 psychiatric outpatients (75 men and 76 women) who
      completed all scales. The mean age of the sample was 45.5 yr. (SD= 12.5), and
      mean education was 16.2 yr. (SD=2.4). Fatigue was inversely correlated with
      education (-.16) and positively correlated with depression (.44), anxiety (.30),
      and alexithymia (.35). However, in a multivariate regression analysis, only
      depression and alexithymia remained significant (p < or = .01).

PMID- 18065076
TI  - The facilitation of important personal goals through exercise.
AB  - In a sample of 1287 adolescents, it appeared that weekly exercise facilitates a
      variety of goals; particularly those related to being or remaining healthy,
      feeling relaxed, not being bored, feeling physically good, not being stressed,
      and attaining high achievements were endorsed. Sedentary and active adolescents
      reported a similar order of 10 specific goals with respect to the likelihood of
      being positively influenced by exercise. The frequency of reported facilitation
      for each of the goals, however, was higher among the active adolescernts. This
      suggests that the more exercise is incorporated in daily life, the more it can be
      regarded as an integral part of the personal goal structure.

PMID- 18065077
TI  - Graded auditory Stroop effects generated by gender words.
AB  - Two auditory Stroop experiments requiring identification of the speaker's sex
      were conducted. An auditory Stroop effect was expected, analogous to visual
      effects found in Stroop literature. In Exp. 1 the speaker's sex was identified
      faster when sex labels ("male" and "female") and words that imply a sex (e.g.,
      father, grandmother) were congruent with the speaker's sex. In Exp. 2, an
      auditory semantic gradient was established in which words that were more
      meaningfully tied to a particular sex produced more Stroop interference. This
      auditory semantic gradient is analogous to effects found in the visual Stroop
      literature of a semantic gradient related to color.

PMID- 18065078
TI  - Are beats gestures unrelated to meaning of verbal production? Comment on
      Mizuguchi's view.
AB  - In a recent note, Mizuguchi (2006) stated that beats are not directly related to
      the meaning of the production of speech. We report a number of studies that
      suggest the existence of a clear relationship between beats and significant parts
      of co-occurring speech.

PMID- 18065079
TI  - Sports participation outside school in total physical activity of children.
AB  - This study of associations of sports participation with perceived and actual
      physical fitness, and total physical activity for 525 10- to 17-yr.-old boys and
      girls in groups of 10-11-yr. (56 boys and 64 girls), 12-13-yr. (68 boys and 68
      girls), 14-15-yr. (70 boys and 71 girls), and 16-17-yr. (68 boys and 60 girls)
      was based on the Physical Activity Index derived from a questionnaire by Telama,
      Leskinen, and Young, and self-perceived endurance, strength, flexibility, and
      body composition. Questions about satisfaction with physical activity,
      participation in organized physical activity and competitions, or watching
      competitions were asked. Two EUROFIT tests were used, the 20-m endurance shuttle
      run and sit-and-reach, plus the sum of 9 skinfold thicknesses. Children who
      participated in organized physical activity and in competitions had a higher
      Physical Activity Index. Passive watching of competitions was not related to
      children's physical activity or their perceived or measured motor abilities.

PMID- 18065080
TI  - Effects of flight workload on urinary catecholamine responses in experienced
      military pilots.
AB  - This study investigated the flight responses induced by strenuous aerobatic
      demonstration flight and an air-to-air combat maneuvering flight in experienced
      pilots. Subjects were 54 military male pilots on a volunteer basis: 8 T-4 pilots
      (M= 35.8 yr., SD=4.9), 15 F-4 pilots (M=32.6 yr., SD=5.1), 13 F-15 pilots (M=33.8
      yr., SD=1.0), and 18 F-2 pilots (M=33.7 yr., SD=3.9). Samples of urine were
      collected approximately 30 min. before and 20 min. after the flights. The
      postflight adrenaline in all pilots was significantly higher than at preflight,
      while a significant increase in noradrenaline at postflight was not observed. The
      post-/preflight ratio of adrenaline in all pilots was relatively similar and
      high. These findings might be regarded as a result of autonomic nervous system
      response to the flight workload of military pilots. Especially is increment in
      sympathetic activity considered to play an important part in psychological
      adaptation to flight.

PMID- 18065081
TI  - Reading and spontaneous speaking fundamental frequency of young Arabic men for
      Arabic and English languages: a comparative study.
AB  - Speaking fundamental frequency (SFF), the average fundamental frequency (lowest
      frequency of a complex periodic sound) measured over the speaking time of a vocal
      or speech task, is a basic acoustic measure in clinical evaluation and treatment
      of voice disorders. Currently, there are few data on acoustic characteristics of
      different sociolinguistic groups, and no published data on the fundamental
      frequency characteristics of Arabic speech. The purpose of this study was to
      obtain preliminary data on the SFF characteristics of a group of normal speaking,
      young Arabic men. 15 native Arabic men (M age = 23.5 yr., SD=2.5) as participants
      received identical experimental treatment. Four speech samples were collected
      from each one, Arabic reading, Arabic spontaneous speech, English reading, and
      English spontaneous speech. Speaking samples, analyzed using the Computerized
      Speech Lab, showed no significant difference for mean SFF between language and
      type of speech and none for mean SFF between languages. A significant difference
      in the mean SFF was found between the types of speech. The SFF used during
      reading was significantly higher than that for spontaneous speech. Also Arabic
      men had higher SFF values than those previously reported for young men in other
      linguistic groups. SFF then might differ among linguistic, dialectical, and
      social groups and such data may provide clinicians information useful in
      evaluation and management of voice.

PMID- 18065082
TI  - Exploring learners' self-efficacy, autonomy and motivation toward e-learning.
AB  - A questionnaire survey was conducted with 116 college students (47 men, 69 women)
      in Central Taiwan to investigate predictive relationships among four attitudinal
      variables, perceived self-efficacy, learners' autonomy, intrinsic motivation, and
      extrinsic motivation toward e-learning. Analysis showed learners' autonomy was
      predictive of both intrinsic (57% independent variance explained) and extrinsic
      motivation (61% independent variance explained). Although perceived self-efficacy
      was not a predictor of intrinsic motivation and extrinsic motivation, it
      correlated significantly with extrinsic motivation.

PMID- 18065083
TI  - Frontal and posterior ERPs related to line bisection.
AB  - The aim of this study was to investigate the dynamic nature of the cortical
      visuospatial attention processes during the line bisection test, which is
      sensitive to perceptual asymmetries. EEGs of 26 normal volunteers were recorded
      during the administration of a computerized line bisection test, which requires
      participants mark the midline of lines using a mouse. Two event-related
      potentials subsequent and time locked to the line presentations, namely, P300 and
      a positive slow wave, were obtained. Findings suggested that both potentials were
      related to the test performance, and the right hemisphere was more active.
      Analysis suggested a right parietotemporal and superior parietal locus for the
      P300 and right prefrontal activity for the positive slow wave. A dynamic
      asymmetrical activity was identified, such that after primary visual perception,
      spatial processing is then initiated in the right parietotemporal cortex and then
      proceeds to the right prefrontal cortex.

PMID- 18065084
TI  - A hierarchical model of approach achievement motivation and effort regulation
      during a 90-min. soccer match.
AB  - Research indicates that effort close to the lactate threshold during a soccer
      match is of importance to succeed, so a prospective study was conducted and a
      hierarchical achievement motivation approach model tested in relation to effort
      reglation among 55 male high level soccer players (M=23.6 yr., SD=4.3). The
      motive to chieve success was expected to be positively associated with the
      mastery goal, which would be positively associated with playing time close to the
      lactate threshold in the irst soccer match period, and this positively associated
      with the same magnitude of effort in the second period. We also examined whether
      the mastery goal would medite the link between the motive to achieve success and
      playing time close to the lactate threshold during the first period and also
      playing time close to the lactate threshold in the first period would mediate the
      link between the mastery goal and playing time at this effort level during the
      second period. LISREL analyses supported these predictions. Additional
      hierarchical polynomial multiple regression analyses indicated unexpected
      significant nonlinear associations between the motive to avoid failure and effort
      regulation. The latter is partly explained by ideas from the catastrophe theory.

PMID- 18065085
TI  - Dream recall frequency by socioeconomic status of Chinese students.
AB  - Whereas the effect of sex and age on dream recall have been studied widely,
      socioeconomic status has rarely been investigated. However, two studies reported
      that higher socioeconomic status was related to greater frequency of dream
      recall. In the present sample of 612 Chinese students from three different
      schools, one elite (high socioeconomic status), one rural (low socioeconomic
      status) and one intermediate, analysis of variance indicated no significant
      association between frequency of dream recall and socioeconomic status.
      Researchers could investigate whether "dream socialization," e.g., encouragement
      of a child to remember his dreams, depends on socioeconomic background, whether
      these processes are mediated by culture.

PMID- 18065086
TI  - Exercise commitment and proneness to eating disorders in a group of physical
      education teachers.
AB  - The study examined the association of exercise commitment with proneness to
      eating disorders in 50 physical education teachers who had been practicing
      various aerobic sports at least three times a week for at least 5 years.
      Significant coefficients were found between Commitment to Exercise Scale scores,
      the number of weekly training sessions, and scores on the Eating Disorders
      Inventory-2 scales measuring Maturity Fears, Social Insecurity, Perfectionism,
      and Asceticism. However, no relationship was found between the Commitment to
      Exercise Scale and the Eating Disorders Inventory-2 variables measuring anorexic
      tendencies (such as Drive for Thinness, Body Dissatisfaction, and Bulimia).
      Findings suggest the presence of some psychological factors common to both
      anorexic tendencies and excessive exercising but not complete overlap, so a
      rather more complex pattern of relationships appears to be mediated by sex and
      personality characteristics.

PMID- 18065087
TI  - Developing ecological research in judo.
AB  - Discussions and exchanges identify axes of research. From an example in
      physiology and perspectives in biomechanics, experimental judo situations nearer
      real ones may yield complementary data from applied and laboratory research.

PMID- 18065088
TI  - Association of depression in mothers of disabled children with the child's
      participation in integrated education.
AB  - To measure depression in mothers of 5 to 7-yr.-old children with disabilities and
      to find out whether mothers' depression varied by sex of the child, 126 mothers
      from Ankara participated; 59 were mothers of children with disabilities who
      participated in integrated education and attended preschool classes in public
      schools and, as a comparison group, 67 were mothers of children with disabilities
      of similar age and characteristics who did not participate in integrated
      education while attending public and private schools. In the study, the Beck
      Depression Scale and General Information Forms were used. Depression in mothers
      of children with disabilities who did not participate in integrated education was
      higher than in mothers of children with disabilities who participated in
      integrated education.

PMID- 18065089
TI  - Futile debate on assessment of field dependence-independence.
AB  - A long-standing debate on assessment has troubled research on field dependence
      independence. The main arguments and a recent measurement proposal by Riding, et
      al., are revised to illustrate the futility of this debate and to defend the
      strength of the cognitive style dimension.

PMID- 18065090
TI  - Prevalence of flying dreams.
AB  - The present study investigated the prevalence of flying dreams in four
      representative German samples of adults (N=5941). Overall, 7.5% of the
      participants reported having flying dreams within the last few months. The
      increase in percentage of persons who report flying dreams from 1956 to 2000
      might reflect the increasing amount of air travel. This would support the
      continuity hypothesis of dreaming.

PMID- 18065091
TI  - Definition of compassion-evoking images in a Mexican sample.
AB  - To assemble a calibrated set of compassion-eliciting visual stimuli, 60
      clinically healthy Mexican volunteers (36 women, 24 men; M age = 27.5 yr., SD =
      2.4) assessed 84 pictures selected from the International Affective Picture
      System catalogue using the dimensions of Valence, Arousal, and Dominance included
      in the Self-assessment Manikin scale and an additional dimension of Compassion.
      Pictures showing suffering in social contexts and expressions of sadness elicited
      similar responses of compassion. The highest compassion response was reported for
      pictures showing illness and pain. Men and women differed in the intensity but
      not the quality of the compassionate responses. Compassion included attributes of
      negative emotions such as displeasure. The quality of the emotional response was
      not different from that previously reported for samples in the U.S.A., Spain, and
      Brazil. A set of 28 pictures was selected as high-compassion-evoking images and
      28 as null-compassion controls suitable for studies designed to ascertain the
      neural substrates of this moral emotion.

PMID- 18065092
TI  - Stability of body image concerns among chinese adolescents: nine-month test
      retest reliabilities of the Negative Physical Self Scale.
AB  - This research assessed the stability of specific body image concerns among
      Chinese adolescents. A sample of 216 boys and 375 girls completed the Negative
      Physical Self Scale, a 38-item measure of body image concerns developed
      specifically for use in Chinese samples. Participants returned nine months later
      to complete the same scale. Bivariate correlation analyses within each sex
      obtained good test-retest reliabilities (r = .48 to r = .78). Findings indicate
      that body image concerns of Chinese adolescents, especially those of girls, are
      relatively stable over a nine-month interval.

PMID- 18065093
TI  - Activity and obesity of Colombian immigrants in Canada who use a food bank.
AB  - The purpose of this study was to provide some preliminary description of the
      Latin-Canadian community by reporting the socioeconomic status, physical
      activity, and weight status (i.e., healthy weight, overweight, or obese status)
      of Colombians newly immigrated to London, Ontario Canada. Face-to-face interviews
      were conducted on a convenience sample of 77 adult Colombian immigrant food bank
      users (46.8% men; mean age 39.9 yr., SD=11.8). Physical activity was gauged using
      the International Physical Activity Questionnaire and self-report Body Mass
      Index, and sociodemographic data were collected. Of respondents, 47% had a
      university education, and 97% received social support. 61% met recommended levels
      of physical activity. Men were more active, being involved in about 130 min. more
      of exercise per week, and more men were overweight than women (63.9% versus
      39.0%, respectively). Of respondents, 73% reported being less active than before
      coming to Canada. This pilot study indicates that Latin-Canadian immigrants are a
      vulnerable group in need of acculturational support. Further study is warranted.

PMID- 18065094
TI  - Entropy and environmental mystery: a parapsychological perspective.
AB  - Findings from parapsychological field studies grounded in cognitive illusions
      parallel the results from Stamps' 2007 research on environmental mystery in
      simulated environments. However, parapsychology also implicates certain
      perceptual-personality characteristics in the perception of some forms of
      environmental mystery. Thus, it is argued that environmental mystery is produced
      fundamentally by an interaction of the right type of percipient (primed to detect
      and give credence to ambiguous stimuli) in the right type of environment (full of
      ambiguous stimuli).

PMID- 18065095
TI  - Anthocyanin- and proanthocyanidin-rich extracts of berries in food supplements-
      analysis with problems.
AB  - The fundamental nutritional benefit of fruit and vegetables in the prevention of
      degenerative diseases--especially in the light of the current "anti-aging wave"-
      has directed the attention of scientists and consumers to a variety of berry
      fruits and their constituents. Many of these fruits, e.g. blueberries,
      elderberries or cranberries, have a long tradition in European and North American
      folk medicine. Based on these experiences and due to the growing interest the
      number of food supplements on the market containing fruit powders, juice
      concentrates or extracts of these fruits has increased considerably. Advertising
      for these products mainly focusses on the phenolic compounds, especially the
      anthocyanins and proanthocyanidins and their preventive effects. Most of the
      preparations are combinations, e.g. of extracts of different fruits with vitamins
      and trace elements, etc. which are labelled in a way which does not allow a
      comparison of the products. Typically, information on the extraction solvent, the
      drug: extract ratio and the content of anthocyanins and proanthocyanidins is
      missing. Besides that, the analysis of these polyphenols causes additional
      problems. Whereas the quality control of herbal medicinal products is regulated
      in detail, no uniform requirements for food supplements are existing. A broad
      spectrum of methods is used for the assay of the constituents, leading to
      differing, incomparable results. In addition to that, the methods are quite
      interference-prone and consequently lead to over- or underestimation of the
      contents. This publication provides an overview of some selected berries
      (lingonberry, cranberry, black elderberry, black chokeberry, black currant,
      blueberry), their constituents and use. The analytical methods currently used for
      the identification and quantification of the polyphenols in these berries are
      described, including an evaluation of their advantages and disadvantages.

PMID- 18065096
TI  - New benzomorphan derivatives of MPCB as MOP and KOP receptor ligands.
AB  - There is considerable interest in developing KOP Opioid receptor ligands as
      clinically useful analgesics. Moreover, compounds with mixed KOP receptor and mu
      opioid peptide (MOP) receptor agonist/antagonist properties could have a better
      therapeutic potential. The benzomorphan-based synthetic ligands MPCB and CCB have
      been shown to bind KOP receptors with high affinity and selectivity. We report
      here a series of compounds synthesized to perform structure-affinity relationship
      (SAR) studies on MPCB. The aim of this study was to optimise KOP receptor-ligand
      interaction and to modulate MOP receptor selectivity. In the benzylamide analogue
      of MPCB (compound 9) the presence of a third aromatic nucleus, at an appropriate
      distance and conformation with respect to aromatic pharmacophoric residues,
      increased KOP receptor affinity by about 6-fold compared to MPCB (Ki = 35 nM and
      Ki = 240 nM, respectively). Instead, compound 28 with a tertiary amino group in
      the nitrogen substituent displayed a comparable KOP receptor affinity (Ki = 179
      nM) but also high MOP receptor affinity (Ki = 45 nM). Thus, the present study
      shows that in benzomorphan-based ligands the presence of different functional
      groups in the nitrogen substituent, ranging from a positive charged amine to an
      additional aromatic ring, is able to promote the correct aligment of aromatic
      pharmacophoric residues with MOP and KOP receptor types. Evaluation of docking
      simulations of compounds 9 and 28 into the KOP and MOP receptor displayed
      selective ligand interactions with the important amino acid residues Tyr320
      (TMVII) and Trp318 (TMVII), respectively.

PMID- 18065097
TI  - Determination of chiglitazar, a dual alpha/gamma peroxisome proliferator
      activated receptor (PPAR) agonist, in human plasma by liquid chromatography
      tandem mass spectrometry.
AB  - Chiglitazar is a dual alpha/gamma peroxisome proliferator-activated receptor
      (PPAR) agonist. A LC-MS/MS method for the determination of chiglitazar was
      developed and validated. The assay used 0.2 mL of plasma. 90% acetonitrile
      containing internal standard was used for protein precipitation. The mobile phase
      contained 70/30 (v/v) of methanol and water at a flow rate of 0.25 mL/min.
      Detection was by negative ion electrospray tandem mass spectrometry on a Sciex
      API 3000. The standard curve, which ranged from 2 to 1500 ng/mL, was fitted to a
      1/x weighted quadratic regression model. The validation results demonstrated that
      the method was sensitive, rapid, selective and robust and provided satisfactory
      precision and accuracy. The method has been successfully used for the analysis of
      clinical samples in pharmacokinetic studies of chiglitazar.

PMID- 18065098
TI  - Stability-indicating spectrophotometric and spectrofluorimetric methods for
      determination of alfuzosin hydrochloride in the presence of its degradation
      products.
AB  - Validated stability-indicating spectrophotometric and spectrofluorimetric assays
      (SIAMs) were developed for the determination of alfuzosin hydrochloride (ALF) in
      the presence of its oxidative, acid, and alkaline degradation products. Three
      spectrophotometric methods were suggested for the determination of ALF in the
      presence of its oxidative degradation product; these included the use of zero
      order (0D), first order (1D), and third order (3D) spectra. The absorbance was
      measured at 330.8 nm for (0D) method, while the amplitude of first derivative
      (1D) method and that of third derivative (3D) method were measured at 354.0 and
      241.2 nm, respectively. The linearity ranges were 1.0-40.0 microg/ml for (0D) and
      (1D) methods, and 1.0-10.0 microg/ml for (3D) method. Two spectrofluorimetric
      methods were developed, one for determination of ALF in the presence of its
      oxidative degradation product and the other for its determination in the presence
      of its acid or alkaline degradation products. The first method was based on
      measuring the native fluorescence of ALF in deionized water using
      lamda(excitation) 325.0 nm and lamda(emission) 390.0 nm. The linearity range was
      50.0-750.0 ng/ml. This method was also used to determine ALF in human plasma with
      the aid of a suggested solid phase extraction method. The second method was used
      for determination of ALF via its acid degradation product. The method was based
      on the reaction of fluorescamine with the primary aliphatic amine group produced
      on the degradation product moiety. The reaction product was determined
      spectrofluorimetrically using lamda(excitation) 380.0 nm and lamda(emission)
      465.0 nm. The linearity range was 100.0-900.0 ng/ml. All methods were validated
      according to the International Conference on Harmonization (ICH) guidelines, and
      applied to bulk powder and pharmaceutical formulations.

PMID- 18065099
TI  - Enantiomeric separation of beta2-agonists on macrocyclic antibiotic chiral
      stationary phases in high performance liquid chromatography.
AB  - The enantiomeric resolution of six beta2-agonists including bambuterol,
      clenbuterol, clenproperol, fumoterol, mabuterol and terbutaline, was studied on
      three macrocyclic antibiotic chiral stationary phases (CSPs): Chirobiotic V, T
      and R. By varying the mobile phase compositions for different CSPs, all the six
      compounds were successfully separated on Chirobiotic V and T CSPs. The
      thermodynamic parameter variation was calculated. The chiral recognition
      mechanism was discussed, the ionic interaction was confirmed to be the most
      dramatic interaction responsible for the chiral recognition. No enantiosepartion
      for all the beta2-agonists was found on Chirobiotic R CSP.

PMID- 18065100
TI  - Studies on the influence of uniformity of particle size of powder, tapping and
      sample replacement for diffusion reflectance quantitative NIR spectrometric
      analysis.
AB  - The extent of deviation factors and the influence of pre-processing of spectra
      for a quantitative application of reflectance NIR measurement against powder
      sample were examined. Lactose monohydrate (NGLM), a medical additive was used for
      this study. Ground lactose monohydrate (GLM) and NGLM were measured by NIR
      reflectance spectroscopy. In the wave number range from 12000 cm(-1) to 4000 cm(
      1), the ratios of absorbance values (a.v.) between the wave numbers of GLM and
      NGLM were almost the same and no influence of intensity of absorbance through the
      measurement range was observed concerning heterogeneity of particle size.
      Absorbance values of NGLM were decreased with increasing number of tapping
      without a bit difference of the change of a.v. The several statistical parameters
      of a.v. from both samples were estimated. The relative standard deviation (RSD)
      and 95% confidence intervals (CIs) of a.v. on successive measurements at a fixed
      position in GLM and NGLM vials were almost the same. However, the RSD and 95%
      confidence of absorbance value of NGLM were larger than these GLM, i.e., RSD:
      0.66% for NGLM, 0.42% for GLM. The 95% of CI of NGLM was ten times larger than
      that of GLM in five replacement positions. The two kinds of baseline corrections,
      the SNV and MSC processing were examined to evaluate the extent of influence
      against a.v. The 95% CI calculated from a.v. by the SNV pre-processing showed a
      wider range compared with that from no pre-processing and MSC pre-processing.
      These results suggest that the statistical confidence of a.v. would also change
      by pre-processing. It is important to consider the statistical confidence of a.v.
      for precise quantitative application of the reflectance NIR spectroscopy.

PMID- 18065101
TI  - Determination of the binding constant of indomethacin-beta-cyclodextrin complex
      by capillary electrophoresis: experimental optimization and temperature study.
AB  - The apparent electrophoretic mobilities of indomethacin in beta-cyclodextrin at a
      range of concentrations were measured directly by capillary electrophoresis.
      Three different linear plots and a non linear plot are proposed for the apparent
      binding constant calculations, based on the fact that the molar ratio of the
      inclusion complex was 1:1. K values obtained at 298 K were 421 M(-1) (double
      reciprocal fit), 488 M(-1) (x-reciprocal fit), 428 M(-1) (y-reciprocal fit) and
      490 M(-1) (non linear fit). The corresponding K values at 313 K were 380 M(-1)
      (double reciprocal fit), 355 M(-1) (x-reciprocal fit), 366 M(-1) (y-reciprocal
      fit) and 339 M(-1) (non linear fit). Using the proposed methods, the binding
      constant of the indomethacin-beta-cyclodextrin inclusion complex can be obtained
      easily. The methods have been applied to obtain the values of the constant K
      under different experimental conditions. Under optimized conditions the K
      constant is temperature dependent and non-arrhenian behaviour was observed.

PMID- 18065102
TI  - In vitro permeation characteristics of moxifloxacin from oil drops through
      excised goat, sheep, buffalo and rabbit corneas.
AB  - The objective of present investigation was to study the in vitro permeation
      characteristics of moxifloxacin from oil drops through freshly excised goat,
      sheep, buffalo and rabbit corneas. Moxifloxacin, 0.043 to 0.048% (w/v) ophthalmic
      solutions with or without (0.5% v/v) benzyl alcohol were made in arachis, castor,
      cottonseed, olive, soybean, sunflower and sesame oils. Permeation studies were
      conducted by putting 1 ml oil formulation on cornea (0.50 cm2) fixed between
      donor and receptor compartments of an all glass modified Franz diffusion cell and
      measuring the drug permeated in receptor (containing 10 ml bicarbonate ringer, pH
      7.4 at 37 degrees C under stirring) by spectrophotometry at 291 nm, after 120
      min. Post permeation corneal hydration was measured to assess corneal damage. The
      study was designed with paired corneas i.e. one cornea of an animal received
      formulation without benzyl alcohol while the contralateral cornea received
      formulation with benzyl alcohol. Moxifloxacin ophthalmic solution in castor oil
      showed maximum permeation with all the corneas. Addition of benzyl alcohol, a
      preservative, to oil drops reduced permeation of moxifloxacin from each oil drop,
      with corneas of all the species. Partition experiments with moxifloxacin oil
      drops and phosphate buffer (pH 7.4) indicated higher partitioning of drug in the
      oil phase, in presence of benzyl alcohol. Thus results of permeation are
      consistent with the partition characteristics of drug between oil and aqueous
      phase. Corneal hydration obtained with all the formulations was between 75 to 80%
      indicating no corneal damage.

PMID- 18065103
TI  - Dissolution properties and characterization of halofantrine-2-hydroxypropyl-beta
      cyclodextrin binary systems.
AB  - Halofantrine (HF) is a poorly water-soluble antimalarial drug with low
      bioavailability. Complex formation of HF.HCl and 2-hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) in aqueous solution and in solid state as well as the
      possibility of improving the solubility and dissolution rate of the drug though
      complexation with the cyclodextrin were investigated. Phase-solubility profile
      indicated that the solubility of the drug was significantly increased in the
      presence of HP-beta-CD and was classified as AL-type, indicating 1:1
      stoichiometric inclusion complexes and an apparent stability constant value of
      2300 M(-1). Solid inclusion complexes of HF, HCl and the cyclodextrin at 1:1
      molar ratios were prepared by physical mixture, kneading, co-evaporation and
      freeze-drying methods and characterized by X-ray diffraction and Infra-red
      spectroscopy. The solubility and dissolution rates of HF.HCl from the complexes
      were determined and found to be dependent on the preparation method of the
      complexes. Dissolution profile of the drug was markedly enhanced by complex
      formation with the cyclodextrin and the product prepared by the freeze-drying
      method exhibited the most superior dissolution properties compared to the other
      methods used in this study. The results suggest that the complexation of HF.HCl
      with HP-beta-CD could improve therapeutic efficacy of the drug though enhanced
      absorption expected from increased drug dissolution.

PMID- 18065104
TI  - Poly(epsilon-caprolactone) microparticles formed by the emulsion-evaporation
      method: effect of the variables of the different steps of the process on their
      size.
AB  - In the present work the influence of the variables of the microencapsulation
      procedure on the size of poly (epsilon-caprolactone) microparticles (PECL-MP)
      obtained by the solvent evaporation method is analysed. This study will allow to
      choose the work conditions necessary to obtain a suitable PECL-MP size for
      parenteral administration. Agitation rate in the emulsion formation step, polymer
      concentration and organic/aqueous phase volume ratio were the variables of the
      microencapsulation procedure that showed a highest influence on the PECL-MP size.
      High polymer concentrations and low internal phase volumes had a negative effect
      on the microencapsulation yield. Neither the conditions of the organic solvent
      evaporation nor the freeze-dry process (when a cryoprotector as threalose was
      used) influenced on PECL-MP size. The usefulness of this study was confirmed by
      getting PECL-MP loaded with naloxone and with a mean diameter within 30-40
      microm, suitable for parenteral administration.

PMID- 18065105
TI  - Pharmacokinetics and safety of recombinant human parathyroid hormone (1-34)
      (teriparatide) after single ascending doses in Chinese healthy volunteers.
AB  - The pharmacokinetics and safety of recombinant human parathyroid hormone (1-34)
      [rhPTH (1-34)] after single ascending doses were evaluated in Chinese healthy
      volunteers. Nine healthy volunteers (five male and four female) were recruited
      for an open label, randomized, three multiply three crossover, single ascending
      dose (10, 20, and 40 microg) study. Using a validated radioimmunoassay, we
      determined the plasma concentrations of rhPTH (1-34). The mean peak plasma
      concentration (Cmax) were 123.6, 195.6, and 318.2 pg x mL(-1) respectively, and
      were reached from 25.6 to 36.1 min after subcutaneous administration. After Cmax
      was reached, the plasma drug level decreased quickly, with elimination halflife
      (t(1/2)) of 53.9 to 64.1 min. The mean AUC(0-infinity) (the area under the plasma
      concentration versus time curve from time zero to infinite) of rhPTH (1-34) were
      11794.2 +/- 974.8, 21606.7 +/- 4753.9, 33877.0 +/- 8374.4 pg x min x mL(-1),
      respectively. The mean AUC(0-t) (the area under the plasma concentration versus
      time curve from time zero to the last quantifiable concentration) of rhPTH (1-34)
      were 9034.4 +/- 1073.9, 17883.3 +/- 4597.1, 31693.5 +/- 6574.8 pg x min x mL(-1),
      respectively. Dose-related linear trend were observed for AUC(o-t) and Cmax of
      rhPTH (1-34). t(1/2) and Tmax (time to Cmax) of rhPTH (1-34) were independent of
      administered dose. rhPTH (1-34) was safe and well tolerated by all volunteers.

PMID- 18065106
TI  - Estrogen-like activities in Vitex species from China determined by a cell based
      proliferation assay.
AB  - Ethanolic extracts of four Chinese medicinally used Vitex species were selected
      and tested for their estrogen-like activities, using an ERalpha-positive MCF-7
      cell based proliferation assay (E-screen assay) and cell cycle analysis (flow
      cytometry). Vitex negundo displayed the highest estrogenic-like activity, and
      could be useful in hormone replacement therapy (HRT).

PMID- 18065108
TI  - Pathophysiological actions of protease activated receptors (PARS).

PMID- 18065109
TI  - Hospital engineering on 'tightrope walk'.
AB  - The way forward for hospital engineering in Europe will clearly require a balance
      between meeting new expectations and adhering to somewhat restrictive budgets.
      This was a point reinforced at ECHE 2007, the 2nd European Conference on
      Healthcare Engineeing, which was held recently in Vienna, Austria. Nicholas
      Marshall reports.

PMID- 18065107
TI  - Comparison of antioxidant activities and total polyphenolic and methylxanthine
      contents between the unripe fruit and leaves of Ilex paraguariensis A. St. Hil.
AB  - Ilex paraguariensis is used in Brazil as a stimulating beverage called "mate".
      Leaves and immature fruit extracts of Ilex paraguariensis were evaluated for
      their radical scavenging capacity, total methylxanthine and polyphenol contents.
      Antimicrobial activity of two enriched saponin fractions obtained from the fruits
      were also evaluated. The radical scavenging activity of the fractioned extracts
      was determined spectrophotometrically using 1,1-diphenylpicrylhydrazyl free
      radical (DPPH). The IC50o of L-ascorbic acid, ethyl acetate and n-butanol
      fractions from the leaves and ethyl acetate fraction from the fruits were 6.48
      microg/mL, 13.26 microg/mL, 27.22 microg/mL, and 285.78 microg/mL, respectively.
      Total methylxanthine content was 1.16 +/- 0.06 mg/g dry weight in the fruits and
      8.78 +/- 0.01 mg/g in the leaves. Total polyphenol content varied from 86.82 +/-
      3 x 10(-4) to 199.91 +/- 3 x 10(-3) mg/g in leaf fractions and from 54.25 +/- 1 x
      10(-3) to 110.36 +/- 4 x 10(-4) mg/g in fruit fractions. Enriched saponin
      fractions from the fruits showed no antimicrobial activity. To our knowledge,
      this are the first data available on the antioxidant/antimicrobial activities and
      polyphenol/methylxanthine contents of Ilex paraguariensis fruits.

PMID- 18065110
TI  - Aligning IT to provide optimum assistance.
AB  - Aladin Antic, head of the IT Division, Vamed Management und Service GmbH
      Deutschland, draws attention to the importance of optimising information
      technology support for tertiary processes in hospitals.

PMID- 18065112
TI  - Meeting child and adolescent needs.
AB  - The preferences of children and adolescents regarding hospital environmental
      characteristics in Iran are studied by Sanaz Litkouhi, Dr Farhang Mozaffar and Dr
      S. Bagher Hoseini of the Iran University of Science and Technology, Tehran, Iran;
      and Prof Dr Eckhart Ribbeck of the Stadtebau-Institut, Universitat Stuttgart,
      Stuttgart, Germany.

PMID- 18065111
TI  - Responding to waste challenges in the NHS.
AB  - Pointers to improving waste management are provided by Greg Roberts, senior
      environmental consultant, Hyder Consulting.

PMID- 18065113
TI  - Extension incorporates 'wow' factor.
AB  - A new extension to Birmingham Children's Hospital has transformed the facility
      that was created in Victorian times, says Hunter Douglas Facade & Sun Control
      Systems.

PMID- 18065114
TI  - Links with nature help recovery.
AB  - Landscape and urban design practice Colour: Urban Design Limited (UDL) is playing
      a major role in two major healthcare projects.

PMID- 18065115
TI  - Legionella infection prevention studied.
AB  - At a recent presentation at the PCT headquarters in Oldham, Dr Tom Makin, of the
      Department of Medical Microbiology, Royal Liverpool University Hospitals,
      described the problems associated with Legionella pneumophila. Health Estate
      Journal reports.

PMID- 18065116
TI  - Boxing clever meets needs precisely.
AB  - Adrian Parkin, Howorth Medical contracts director, examines the benefits of using
      a modular approach to operating theatre construction and recommends putting a box
      around what is designed rather than designing to fit a box.

PMID- 18065117
TI  - NAHFO objectives outlined.
AB  - The National Association of Healthcare Fire Officers sets outs its aims and
      objectives.

PMID- 18065118
TI  - Music and cancer pain management.
AB  - PROBLEM: When coupled with the often debilitating side-effects of pharmacological
      interventions, chronic cancer pain may elicit feelings of anxiety and depression
      and therefore adversely affect patient well-being and quality of life. PURPOSE:
      This review article is a systematic assessment of the published literature
      related to music and cancer pain management. METHOD: A comprehensive systematic
      evaluation of the data based literature was undertaken and analyzed using matrix
      analysis. RESULTS: As an adjunctive form of pain management, music therapy has
      been shown to address some of these hardships by providing patients with an
      alternative effective means by which to reduce their subjective experiences of
      pain. Studies investigating the efficacy of music therapy during invasive cancer
      procedures and chemotherapy demonstrated the role that attention states play in
      distracting patients from, and therefore minimizing their experience of, the pain
      associated with such treatments. Other studies examining diverse outpatient
      populations revealed similar findings, illustrating well the cognitive-affective
      dimensions of pain perception. Although these findings fail to adequately address
      the ambiguity surrounding music therapy's role in cancer pain management, music
      therapy has nonetheless been shown to significantly reduce anxiety and, in so
      doing, indirectly lessen the intensity of pain while improving patient quality of
      life.

PMID- 18065119
TI  - A snapshot of bronchiolitis in Hawaiian children: winter 2005.

PMID- 18065120
TI  - Comparison of cleft lip only and cleft lip and palate, Hawai'i, 1986-2003.
AB  - Using birth defects registry data, this investigation compared cleft lip only
      (CLO) and cleft lip and palate (CLP). CLP cases were more likely than CLO cases
      to expire after birth (3.2% versus 1.0%), be boys (68.0% versus 56.5%), Pacific
      Islander (26.5% versus 16.4%), have lower birth weight (20.4% versus 11.1%), and
      lower gestational age (22.6% versus 20.4%).

PMID- 18065121
TI  - Issues in medical malpractice XVII.

PMID- 18065122
TI  - Talking about psychiatric medications: a parent-to-parent perspective (for
      children and youth) part I.
AB  - This article presents a format for parent-to-parent and parent-to-professional
      guidance on psychiatric medications for children and youth. It reviews progress
      in Hawai'i's system of care for child mental health. Between 1999 and 2006,
      Hawai'i had nationally and internationally renowned experts in psychiatric
      medication conduct CME for Hawai'i's primary care and specialist care physicians.
      These conferences have included consumers and non-physician mental health
      colleagues. The importance of involvement of consumers in the process of rational
      decision-making for the individual child or youth is an emphasis in the system of
      care in Hawai'i. The approach featured in Susan Cooper's "Meditation on
      Medication" presentation in the 2005 symposium breakout for parents demonstrates
      the genuine collaboration with consumers that may be a partial remedy for the
      data that shows an overall poor adherence to prescribed interventions.

PMID- 18065123
TI  - Broken heart syndrome--a critical review of transient left ventricular apical
      ballooning.
AB  - Transient left ventricular apical ballooning (TLVAB) is a recently proposed
      clinical entity that mimics an acute coronary syndrome in its clinical
      presentation. Retrospective studies suggest that it may account for 1% of
      myocardial infarction diagnoses. We provide a review of TLVAB including its
      clinical presentation, diagnostic studies, etiology, pathogenesis, criticism,
      complications, and management.

PMID- 18065124
TI  - Intimate partner violence: perceptions of Chuukese women.
AB  - PURPOSE: This qualitative study examined Chuukese women's views about Intimate
      Partner Violence (IPV). METHODS: Focus groups were conducted in Chuukese. Themes
      emerged from content analysis. RESULTS: Migration may disrupt protective cultural
      practices. Cultural norms place the responsibility for family peace on the women
      who perceive that IPV is closely linked with marital infidelity. IMPLICATIONS:
      Understanding cultural practices is important in addressing IPV.

PMID- 18065125
TI  - RTOG clinical trials for prostate cancer.

PMID- 18065126
TI  - Issues in medical malpractice XVI.

PMID- 18065127
TI  - Nursing negligence: $5 million punitive damage award. Mobile Infirmary Assn. v.
      Tyler, 2007 ASC 1041484 (09/14/07) So.2D -AL.

PMID- 18065128
TI  - Should nurses have advocated for a cesarean delivery? Case on point: Dixon v.
      Crete Medical Clinic, P.C., (08/17/07) FED 8 F.3d -NB..

PMID- 18065129
TI  - AR: RN claimed comp. for prolapsed uterus: denial of benefits affirmed-failure to
      prove case. Rodriguez v. Lakewood Plaza Nursing Center, 2007 ARCA (10/03/07)
      S.W.3d -AR.

PMID- 18065130
TI  - Was Board arbitrary/capricious in suspending license? Case on point: Miller v.
      Tennessee Bd. of Nsg.,2007 TNCIV M2005-02383 -COA-R3 S. W.3d -TN.

PMID- 18065131
TI  - Pinching off syndrome in free-ranging white-tailed sea eagles (Haliaeetus
      albicilla) in Europe: frequency and geographic distribution of a generalized
      feather abnormality.
AB  - Generalized feather abnormalities are rarely documented in free-living birds.
      Pinching off syndrome (POS) is a feather abnormality in which all remiges and
      retrices become malformed and are lost during the nestling stage, rendering the
      bird unable to fly. To determine the frequency of occurrence and geographic
      distribution of this syndrome in white-tailed sea eagles (Haliaeetus albicilla)
      in Europe, we sent questionnaires to ornithologists in 19 countries within the
      European range of this species. We also searched for reported cases of sea eagles
      with feather abnormalities that met the criteria of POS. Overall, 32 nestlings or
      fledglings with POS were identified between 1975 and 2006. The geographic
      distribution of cases was primarily restricted to 4 European countries: Germany
      (17 cases), Poland (11 cases), the Czech Republic (3 cases), and Great Britain (1
      case). Eleven eagles from Germany and 2 eagles from the Czech Republic were
      examined clinically. In 15 birds in which sex was determined, 8 were female and 7
      were male. From 2000 to 2005, the 5-year incidence of POS in white-tailed sea
      eagles in Germany was 3.5 cases per 1000 birds. Although the etiology of this
      syndrome in wild sea eagles is unknown, our results support a possible genetic
      cause.

PMID- 18065132
TI  - Pharmacokinetic disposition of the oral iron chelator deferiprone in the white
      leghorn chicken.
AB  - Deferiprone is a bidentate oral iron chelator used for the treatment of
      transfusional iron overload in people. The purpose of this study was to determine
      the pharmacokinetic disposition of deferiprone in the white leghorn chicken as a
      potential model upon which to base therapeutic regimens for the treatment of iron
      storage disease (hemochromatosis) in affected avian species. A suspension of
      deferiprone (DFP) was administered orally at a single dose of 50 mg/kg to 10
      birds that were iron-loaded (IL-DFP) and 10 non--iron-loaded control birds (NIL
      DFP). After a 30-day washout period, 5 birds from the NIL-DFP group were used for
      a bioavailability study of deferiprone administered intravenously at the same
      dose. Blood samples were collected at varying intervals over a 24-hour period and
      were analyzed for deferiprone by high-performance liquid chromatography, then
      plasma concentration versus time curves were developed. Deferiprone was rapidly
      absorbed from the gastrointestinal tract of the chicken, with plasma
      concentrations effective for iron chelation in humans (>20 micromol/L) maintained
      for at least 8 hours after oral dosing. The half-life (mean +/- SD) of the orally
      administered deferiprone in the IL-DFP and NIL-DFP groups was 2.91 +/- 0.78 hours
      and 3.61 +/- 0.90 hours, respectively, and was 2.42 +/- 0.24 hours for
      deferiprone administered intravenously. The mean oral bioavailability was 93%.
      Deferiprone is well absorbed and widely distributed in the chicken, with a longer
      half-life than reported in mammals.

PMID- 18065133
TI  - Pharmacokinetic disposition of the oral iron chelator deferiprone in the domestic
      pigeon (Columba livia).
AB  - Deferiprone is a bidentate oral iron chelator used for the treatment of iron
      overload in people. The purpose of this study was to determine the
      pharmacokinetic disposition of deferiprone in the domestic pigeon (Columba livia)
      and to compare the results with a previous study in the white leghorn chicken.
      Deferiprone (DFP) was administered orally as a suspension at a single dose of 50
      mg/kg to 10 iron-loaded (IL-DFP) pigeons and 10 non--iron-loaded controls (NIL
      DFP). Six NIL-DFP birds were also administered deferiprone intravenously to
      determine the bioavailability of the drug after a 30-day washout period. To
      evaluate if deferiprone induces its own metabolism, the pharmacokinetic
      disposition of the drug was also studied in the IL-DFP group after oral therapy
      with deferiprone at a dosage of 50 mg/kg q12h for 30 days. For each phase,
      collected blood was analyzed for deferiprone by high-performance liquid
      chromatography to develop a plasma concentration versus time curve. Deferiprone
      was rapidly absorbed from the gastrointestinal tract, with plasma concentrations
      effective for iron chelation maintained for at least 8 hours after administration
      in iron-loaded birds. The half-life (mean +/- SD) for deferiprone given orally to
      the IL-DFP and NIL-DFP groups was 2.98 +/- 0.85 hours and 3.26 +/- 1.25 hours,
      respectively, and when intravenously administered was 3.79 +/- 1.23 hours. The
      half-life after 30 days of treatment was 3.42 +/- 1.18 hours. Oral
      bioavailability was 44%. This study demonstrated that oral absorption of
      deferiprone is acceptable, it does not induce its own metabolism, and the drug
      was widely distributed in the pigeon, as it was in the chicken, with a longer
      half-life than that reported in mammals. Minor interspecies variations in the
      pharmacokinetics of deferiprone exist between chickens and pigeons.

PMID- 18065134
TI  - Plasma uric acid, creatinine, and urea nitrogen concentrations after whole blood
      administration via the gastrointestinal tract in domestic pigeons (Columba
      livia).
AB  - To determine if blood administered to pigeons by gavage tube would simulate
      gastrointestinal hemorrhage in a noncarnivorous avian model, be digested in the
      gastrointestinal tract, and subsequently alter concentrations of plasma urea
      nitrogen, creatinine, or uric acid, blood from common peacocks (Pavo cristatus)
      was administered by gavage tube to 5 healthy domestic pigeons (Columba livia) at
      doses of 0.5, 1.0, 2.0, 4.0, and 8.0 ml/kg. No significant difference in plasma
      concentrations of urea nitrogen, creatinine, or uric acid was seen 4-6 hours
      after gavage. The findings did not support or rule out the presence of
      gastrointestinal blood in pigeons as a model for hemorrhage in noncarnivorous
      avian species.

PMID- 18065135
TI  - Falcon adenovirus in an American kestrel (Falco sparverius).
AB  - A fatal adenovirus infection is described in a wild-caught American kestrel
      (Falco sparverius). Predominate lesions were a moderate to severe hepatitis with
      diffuse single-cell necrosis of hepatocytes and a splenitis characterized by
      necrosis of cells surrounding the sheathed arteries. Pan-nuclear eosinophilic to
      magenta inclusion bodies were abundant within hepatocytes. Polymerase chain
      reaction was used to amplify a portion of the hexon gene from DNA extracted from
      the bird's liver and spleen. Sequence analysis showed that the adenovirus
      infecting this kestrel was the falcon adenovirus with a sequence homology of
      99.5% to the isolate from the Northern aplomado falcon (Falco femoralis) variant
      and 98.6% homology to isolates from the taita (Falco fasciinucha) and orange
      breasted falcons (Falco deiroleucus). This report expands the range of species of
      falcons that are susceptible to falcon adenovirus infection and disease. Given
      that this kestrel was recently wild caught and housed in isolation with other
      wild-caught kestrels, it is likely that the falcon adenovirus is present in wild
      populations of American kestrels.

PMID- 18065136
TI  - Endocrine pancreatic insufficiency secondary to chronic herpesvirus pancreatitis
      in a cockatiel (Nymphicus hollandicus).
AB  - A cockatiel (Nymphicus hollandicus) examined because of weight loss, polydipsia,
      and polyuria was diagnosed with diabetes mellitus based on the presence of
      glucosuria and marked hyperglycemia. Medical attempts to manage the diabetes
      mellitus were unsuccessful, and the bird was euthanatized. Histopathologic
      examination of the pancreas revealed a chronic active pancreatitis with
      herpesviral inclusions in many of the pancreatic acinar and duct cells. Psittacid
      herpesvirus-1 (PsHV-1) DNA was amplified from the lesion by polymerase chain
      reaction. Sequencing of the amplicon showed it to be the genotype 1 variant,
      which is most commonly associated with Pacheco's disease, an acute rapidly fatal
      systemic infection. The findings in this case suggest that the PsHV-1 genotype
      may also cause a localized disease of the pancreas. Infection with this virus
      should be considered as a differential diagnosis in birds with pancreatitis with
      or without diabetes mellitus.

PMID- 18065137
TI  - Infiltrative lipoma in a blue-crowned conure (Aratinga acuticaudata).
AB  - A 14-year-old blue-crowned conure (Aratinga acuticaudata) of unknown sex was
      brought to the hospital with a 3-week history of straining and vocalizing during
      defecation. Physical examination revealed blood and urate staining on feathers
      around the cloaca. A 2.5-cm subcutaneous swelling was palpated along the midline
      of the caudoventral abdomen. During surgical exploratory, a subcutaneous soft
      tissue mass was found, which extended through the body wall musculature and into
      the coelomic cavity. The abnormal tissue was adhered to the cloacal serosa,
      causing deviation of the cloaca caudally and ventrally. The mass was excised and
      submitted for histopathology, and the histopathologic diagnosis was infiltrative
      lipoma. The surgical incision healed uneventfully, and no evidence of tumor
      regrowth was apparent 7 months after surgery. This is the first documented case
      of infiltrative lipoma in a bird.

PMID- 18065138
TI  - Tracheal resection and anastomosis in a mallard duck (Anas platyrhynchos) with
      traumatic segmental tracheal collapse.
AB  - A male mallard duck (Anas platyrhynchos) presented for examination for acute
      respiratory distress and lethargy. The duck had experienced recurrent episodes of
      respiratory distress since being attacked by a raccoon the previous year,
      resulting in neck lacerations. Diagnostic tests, including a complete blood
      count, plasma biochemical analysis, radiography, and tracheoscopy, revealed a
      collapsed trachea. Surgical correction of the collapsed tracheal segment resulted
      in resection of 9% of the total tracheal length and subsequent anastomosis.
      Tracheoscopy performed 2 and 3 months after surgery revealed a healthy mucosa,
      minimal reduction of the tracheal lumen in the area of anastomosis, and minimal
      suture granuloma formation.

PMID- 18065139
TI  - Everyone's doing it: avian and exotic pet referrals.

PMID- 18065140
TI  - What is your diagnosis? Proventriculus and food material in the gizzard.

PMID- 18065141
TI  - Being proactive in shaping the future of rehabilitation nursing.

PMID- 18065142
TI  - How to parent chronically ill school-aged children and their siblings.

PMID- 18065143
TI  - Adherence to therapy: using an evidence-based protocol.
AB  - The number of patients receiving injectable medications has increased
      significantly during the past few years. Today, patients with hepatitis,
      rheumatoid arthritis, and multiple sclerosis are added to the list of those,
      namely diabetics, who have been instructed in self-administration of injectable
      medications. Currently, some of these medications create significant skin site
      reactions, and patients tend to discontinue the medications without informing the
      healthcare provider. Determining the problem and developing a research study that
      provides evidence to demonstrate methods to help patients adhere to agreed-upon
      treatment modalities can be accomplished within the clinical practice setting.
      This study provided a method to decrease skin reactions with interferon 1-b
      injections for multiple sclerosis patients and has been continued as a method
      with other like medications.

PMID- 18065144
TI  - Discriminating high fall risk on an inpatient rehabilitation unit.
AB  - The objective of this study was to identify on admission the most discriminating
      fall predictors for patients to an inpatient rehabilitation unit. Medical
      information from 34 patients who fell over a consecutive 7-month period and 102
      controls (1:3 ratio) matched for diagnosis, age, and gender was analyzed to
      identify a set of best predictors. Admission mobility and problem solving FIM
      scores accounted for 17% of variance in whether a fall occurred during the
      admission. After statistically deriving optimal cutoff thresholds for decision
      making, high fall risk was retroactively assigned to patients. Logistic
      regression revealed increased odds of having fallen by 5.1 times for poorer
      mobility and 2.4 times for poorer problem solving. The practical benefits of the
      evidence-based risk assessment were discussed.

PMID- 18065145
TI  - Life changes in individuals diagnosed with sleep apnea while accommodating to
      continuous positive airway pressure (CPAP) devices.
AB  - Continuous positive airway pressure (CPAP) devices are effective in preventing
      the sequela of obstructive sleep apnea (OSA); however, compliance with the device
      is problematic. This study's purpose is to longitudinally discover OSA patients
      experiences with CPAP. A hermeneutic phenomenological approach was used to obtain
      narrative stories for interpretive analysis. 20 patients were prescribed CPAP at
      an urban sleep center Five themes and one constitutive pattern included (1)
      trouble using CPAP, (2) needing to persist through initial and recurring
      frustration, (3) difficulty recognizing subtle improvements, (4) accessing help
      and problem solving, and (5) becoming part of the routine or abandoning the
      device. Perseverence through tribulations by developing a positive mind-set was
      the constitutive pattern. The implications are that rehabilitation nurses should
      understand the difficulties with CPAP compliance so that they may assist patients
      with device issues and offer encouragement.

PMID- 18065146
TI  - Research insights.

PMID- 18065147
TI  - Barriers and facilitators to exercise among stroke survivors.
AB  - Physical activity after stroke may prevent disability and stroke recurrence; yet,
      physical impairments may inhibit poststroke exercise and subsequently limit
      recovery. The goal of this study was to elicit barriers to and facilitators of
      exercise after stroke. We conducted three focus groups and achieved content
      saturation from 13 stroke survivors--eight men and five women--85% of whom were
      African American and 15% White, with a mean age of 59 years. We coded and
      analyzed the transcripts from the focus groups for common themes. Participants
      across groups reported three barriers (physical impairments from stroke, lack of
      motivation, and environmental factors) and three facilitators (motivation, social
      support, and planned activities to fill empty schedule) to exercise after stroke.
      Exercise activity can provide a purpose and structure to a stroke survivor's
      daily schedule, which may be interrupted after stroke. In addition, receiving
      social support from peers and providers, as well as offering stroke-specific
      exercise programming, may enhance physical activity of stroke survivors including
      those with disabilities. We intend to incorporate these findings into a post
      stroke self-management exercise program.

PMID- 18065148
TI  - Protection against high-dose homologous infection in calves immunized with
      intestine or membrane extracts from Haemonchus placei.
AB  - Control of Haemonchus placei, one of the most important cattle nematodes in
      Brazil, relies on the use of anthelmintics. However, there is a need for
      integrated control, which includes active immunization. The aim of this work was
      to assess the protection afforded to calves by immunization with adult H. placei
      extracts against a high-dose challenge infection, a condition frequently found in
      the tropics. Holstein calves aged 8-10 months were immunized four times with
      intestinal extracts (Group D) or with a Triton X-100-soluble fraction of adult H.
      placei (Group A), challenge-infected with 120,000 infective larvae and sacrificed
      40 days later. Immunized animals had higher IgG titers than the controls against
      tested fractions after the 2nd immunization, peaking after the 4th. Sera from
      both immunized groups recognized bands of similar apparent mass in both antigenic
      preparations, some of which were similar in molecular weight to Haemonchus
      contortus antigens with known protective effect to sheep. Egg counts were 49% and
      57% lower in Groups A and D than in controls, respectively. High levels of
      protection were observed in two of the four calves in Group D, as evidenced by
      very low worm numbers recovered at necropsy, absence of eggs in the uteri of the
      recovered females and reduced worm length. Group D animals also showed milder
      signs of anemia than the other infected animals. Results demonstrate that
      protection against homologous high-dose challenge can be achieved by immunizing
      calves with H. placei gut antigens.

PMID- 18065149
TI  - Layer selective presynaptic modulation of excitatory inputs to hippocampal cornu
      Ammon 1 by mu-opioid receptor activation.
AB  - Chronic and acute activation of mu-opioid receptors (MOR) in hippocampal cornu
      Ammon 1 (CA1) disrupts rhythmic activity, alters activity-dependent synaptic
      plasticity and impairs spatial memory formation. In CA1, MORs act by
      hyperpolarizing inhibitory interneurons and suppressing inhibitory synaptic
      transmission. MOR modulation of inhibitory synaptic function translates into an
      increase in excitatory activity in all layers of CA1. However, the exact
      anatomical sites for MOR actions are not completely known. Therefore, we used
      voltage-sensitive dye imaging, whole cell patch clamping, photolysis of alpha
      carboxy-2-nitrobenzyl ester, trifluoroacetic acid salt (CNB) -caged GABA, and
      micro-sectioned slices of rat hippocampus to investigate the effect of MOR
      activation in CA1. First, we investigated the effect of MOR activation using a
      MOR agonist [d-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO) on the direct
      activation of GABA receptors by photolysis of CNB-caged GABA in all layers of
      CA1. MOR activation did not affect hyperpolarizations due to direct GABA receptor
      activation in any layer of CA1, but MOR activation did suppress GABAergic
      inhibitory postsynaptic potentials suggesting that MOR activation acts by
      presynaptically inhibiting interneuron function. We next examined whether MOR
      activation was equivalently effective in all anatomical layers of CA1. To do
      this, cuts were made between anatomical layers of CA1 and isolated layers were
      stimulated electrically (five pulses at 20 Hz) to produce excitatory postsynaptic
      potentials (EPSPs). Under these conditions, MOR activation significantly
      increased EPSP areas in stratum radiatum (SR), stratum pyramidale (SP) and
      stratum oriens (SO) relative to stratum lacunosum-moleculare (SLM). When compared
      with the effect of GABA(A) and GABA(B) receptor antagonists on EPSP areas, the
      effect of DAMGO was proportionately larger in SR, SP and SO than in SLM. We
      conclude that MOR activation is more effective at directly modulating activity in
      SR, SP and SO, and the smaller effect in SLM is likely due to a smaller MOR
      inhibition of GABA release in SLM.

PMID- 18065150
TI  - The effects of photic and nonphotic stimuli in the 5-HT7 receptor knockout mouse.
AB  - 5-HT and agonists of the 5-HT receptor can modify the response of the mammalian
      pacemaker, which is located in the hypothalamic suprachiasmatic nuclei (SCN), to
      photic and nonphotic stimulation. Previous studies suggest that the 5-HT7
      receptor is involved in the regulation of photic input, and the modulation of
      nonphotic circadian resetting of the circadian clock. The present study
      investigated the role of the 5-HT7 receptor by evaluating a wide variety of
      circadian parameters in mice lacking a functional allele for this receptor (5-HT7
      knockout (KO)) compared with wild type (WT) animals that were bred on the same
      genetic background, including rate of entrainment, photic responsiveness and
      nonphotic response to a serotonergic agonist. No significant differences were
      detected in the average number of days 5-HT7 KO mice needed to reach entrainment
      to an advance of 6 h in the LD cycle compared with WT animals. Further, we
      investigated the acute responsiveness of both groups of mice to acute light
      stimulation at various times (circadian time (CT) 0, 6, 9, 12, 14, 16, 18, 20 and
      22). A significant difference in the phase resetting response to light between
      the groups was revealed at CT22. Finally, as the 5-HT7 receptor has been
      associated with the modulation of nonphotic resetting in vitro, we examined the
      response of the 5-HT7 KO mice to systemic administration of a 5-HT(1A/7) agonist.
      The current study is the first to demonstrate the elimination of a nonphotic
      response to (+) 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in mice
      lacking the 5-HT7 receptor compared with WT animals in vivo. Taken together, the
      present findings provide additional evidence that reform the established view on
      the role of the 5-HT7 in the photic regulation of retinohypothalamic (RHT) input,
      and support further the involvement of the 5-HT7 receptor in the modulation of
      nonphotic resetting in circadian clock.

PMID- 18065151
TI  - Chronic erythropoietin-mediated effects on the expression of astrocyte markers in
      a rat model of contusive spinal cord injury.
AB  - Using a standardized rat model of contusive spinal cord injury (SCI; [Gorio A,
      Gokmen N, Erbayraktar S, Yilmaz O, Madaschi L, Cichetti C, Di Giulio AM, Vardar
      E, Cerami A, Brines M (2002) Recombinant human erythropoietin counteracts
      secondary injury and markedly enhances neurological recovery from experimental
      spinal cord trauma. Proc Natl Acad Sci U S A 99:9450-9455]), we previously showed
      that the administration of recombinant human erythropoietin (rhEPO) improves both
      tissue sparing and locomotory outcome. In the present study, to better understand
      rhEPO-mediated effects on chronic astrocyte response to SCI in rat, we have used
      immunocytochemical methods combined with confocal and electron microscopy to
      investigate, 1 month after injury, the effects of a single rhEPO administration
      on the expression of a) aquaporin 4 (AQP4), the main astrocytic water channel
      implicated in edema development and resolution, and two molecules (dystrophin and
      syntrophin) involved in its membrane anchoring; b) glial fibrillary acidic
      protein (GFAP) and vimentin as markers of astrogliosis; c) chondroitin sulfate
      proteoglycans of the extracellular matrix which are upregulated after SCI and can
      inhibit axonal regeneration and influence neuronal and glial properties. Our
      results show that rhEPO administration after SCI modifies astrocytic response to
      injury by increasing AQP4 immunoreactivity in the spinal cord, but not in the
      brain, without apparent modifications of dystrophin and syntrophin distribution.
      Attenuation of astrogliosis, demonstrated by the semiquantitative analysis of
      GFAP labeling, was associated with a reduction of phosphacan/RPTP zeta/beta,
      whereas the levels of lecticans remained unchanged. Finally, the relative volume
      of a microvessel fraction was significantly increased, indicating a pro
      angiogenetic or a vasodilatory effect of rhEPO. These changes were consistently
      associated with remarkable reduction of lesion size and with improvement in
      tissue preservation and locomotor recovery, confirming previous observations and
      underscoring the potentiality of rhEPO for the therapeutic management of SCI.

PMID- 18065152
TI  - Alterations in attentional mechanisms in response to acute inflammatory pain and
      morphine administration.
AB  - Research indicates that pain negatively impacts attention; however, the extent of
      this impact and the mechanisms of the effect of pain on normal attentional
      processing remain unclear. This study 1) examined the impact of acute
      inflammatory pain on attentional processing, 2) examined the impact of morphine
      on attentional processing, and 3) determined if an analgesic dose of morphine
      would return attentional processing to normal levels. Male Sprague-Dawley rats
      were trained on the 5 choice serial reaction time task (5CSRTT), a test commonly
      used to assess the attentional mechanisms of rodents. Animals were injected with
      saline or 1, 3, or 6 mg/kg of morphine. Twenty minutes later, animals received a
      formalin (or saline) injection into one hind paw to induce an inflammatory
      condition and were then immediately tested in the 5CSRTT. The results show that
      the formalin injection significantly impaired performance, as measured by an
      increase in the number of trials in which the animal failed to attend to the
      task. Likewise, a high dose of morphine (6 mg/kg) produced similar decrements in
      task performance. Of primary importance is that 3 mg/kg of morphine produced
      analgesia with only mild sedation, and performance in the 5CSRTT was improved
      with this dose. This is the first study to use an animal model of acute pain to
      demonstrate the negative impact of pain on attention, and provides a novel
      approach to examine the neural correlates that underlie the disruptive impact of
      pain on attention.

PMID- 18065153
TI  - Convergence of unimodal and polymodal sensory input to the entorhinal cortex in
      the fascicularis monkey.
AB  - The hippocampal formation is a key structure in memory formation and
      consolidation. The hippocampus receives information from different cortical and
      subcortical sources. Cortical information is mostly funneled to the hippocampus
      through the entorhinal cortex (EC) in a bi-directional way that ultimately ends
      in the cortex. Retrograde tracing studies in the nonhuman primate indicate that
      more than two-thirds of the cortical afferents to the EC come from polymodal
      sensory association areas. Although some evidence for the projection from visual
      unimodal cortex to the EC exists, inputs from other visual and auditory unimodal
      association areas, and the possibility of their convergence with polymodal input
      in the EC remains largely undisclosed. We studied 10 Macaca fascicularis monkeys
      in which cortical deposits of the anterograde tracer biotinylated dextran-amine
      were made into different portions of visual and auditory unimodal association
      cortices in the temporal lobe, and in polymodal association cortex at the upper
      bank of the superior temporal sulcus. Visual and auditory unimodal as well as
      polymodal cortical areas projected to the EC. Both visual unimodal and polymodal
      association cortices presented dense projections, while those from unimodal
      auditory association cortex were more patchy and less dense. In all instances,
      the projection distributed in both the superficial and deep layers of the EC.
      However, while polymodal cortex projected to all layers (including layer I),
      visual unimodal cortex did not project to layer I, and auditory unimodal cortex
      projected less densely, scattered through all layers. Topographically,
      convergence from the three cortical areas studied can be observed in the lateral
      rostral and lateral caudal subfields. The present study suggests that unimodal
      and polymodal association cortical inputs converge in the lateral EC, thereby
      providing the possibility for the integration of complex stimuli for internal
      representations in declarative memory elaboration.

PMID- 18065154
TI  - Vascular endothelial growth factor is up-regulated after status epilepticus and
      protects against seizure-induced neuronal loss in hippocampus.
AB  - Vascular endothelial growth factor (VEGF) is a protein factor which has been
      found to play a significant role in both normal and pathological states. Its role
      as an angiogenic factor is well-established. More recently, VEGF has been shown
      to protect neurons from cell death both in vivo and in vitro. While VEGF's
      potential as a protective factor has been demonstrated in hypoxia-ischemia, in
      vitro excitotoxicity, and motor neuron degeneration, its role in seizure-induced
      cell loss has received little attention. A potential role in seizures is
      suggested by Newton et al.'s [Newton SS, Collier EF, Hunsberger J, Adams D,
      Terwilliger R, Selvanayagam E, Duman RS (2003) Gene profile of electroconvulsive
      seizures: Induction of neurotrophic and angiogenic factors. J Neurosci 23:10841
      10851] finding that VEGF mRNA increases in areas of the brain that are
      susceptible to cell loss after electroconvulsive-shock induced seizures. Because
      a linear relationship does not always exist between expression of mRNA and
      protein, we investigated whether VEGF protein expression increased after
      pilocarpine-induced status epilepticus. In addition, we administered exogenous
      VEGF in one experiment and blocked endogenous VEGF in another to determine
      whether VEGF exerts a neuroprotective effect against status epilepticus-induced
      cell loss in one vulnerable brain region, the rat hippocampus. Our data revealed
      that VEGF is dramatically up-regulated in neurons and glia in hippocampus,
      thalamus, amygdala, and neocortex 24 h after status epilepticus. VEGF induced
      significant preservation of hippocampal neurons, suggesting that VEGF may play a
      neuroprotective role following status epilepticus.

PMID- 18065155
TI  - Nongenomic regulation of glutamatergic neurotransmission in hippocampus by
      thyroid hormones.
AB  - Thyroid hormones (THs) are well known for their genomic effects but recently
      attention has focused also on their nongenomic actions as rapid modulators of
      membrane receptors. Here we show that thyroxine (T4) and 3,3',5'-l
      triiodothyronine (T3) rapidly decrease N-methyl-d-aspartate (NMDA)-evoked
      currents in rat hippocampal cultures with potency in the micromolar range. The
      effect is not mediated by glutamate or glycine binding sites as an increase in
      agonist or glycine concentration does not alter TH potencies. Furthermore THs'
      effect on NMDA receptors is independent of voltage and of subunit composition.
      The mechanism of THs' antagonistic effect does not involve PKC phosphorylation of
      NMDA receptors since neither blocking nor stimulating PKC changed THs'
      modulation. T3, but not T4, inhibits also kainate-evoked currents in hippocampal
      neurons in culture. In hippocampal pyramidal neurons in slice, T3, but not T4,
      significantly reduced the frequency of miniature excitatory postsynaptic currents
      (mEPSCs) without affecting their amplitude and decay. In cultured rat cortical
      neurons THs prevented glutamate-induced neuronal death at concentrations similar
      to those effective on glutamatergic receptors. Taken together our data show for
      the first time that THs can rapidly affect ionotropic glutamatergic receptors in
      hippocampal neurons, an effect that could have an important role in their
      modulation of brain function in physiological and pathological states.

PMID- 18065157
TI  - Morphological characterization of rat Mas-related G-protein-coupled receptor C
      and functional analysis of agonists.
AB  - A recently described family of "orphan" receptors, called Mas-related G-protein
      coupled receptors (Mrg), is preferentially expressed in small nociceptive neurons
      of the rodent and human dorsal root ganglia (DRG). Mrg are activated by high
      affinity peptide fragments derived from the proenkephalin A gene, e.g. BAM22
      (bovine adrenal medullary). To study the histological distribution and functional
      properties of these receptors, we combined confocal immunohistochemistry in rat
      DRG and dermis whole mounts, using new antibodies against the rat Mas-related G
      protein-coupled receptor C (MrgC), with single-fiber recordings and neurochemical
      experiments using isolated hind-paw skin and sciatic nerve. In lumbar DRG we
      found cytoplasmic MrgC labeling mainly in small- and medium-sized neurons;
      coexpression with isolectin B4 (46%) and transient receptor potential vanilloid
      receptor 1 channel protein (TRPV1) (52%) occurred frequently, whereas calcitonin
      gene-related peptide (CGRP) was rarely colocalized with MrgC in DRG (11%) and
      dermal nerve fibers (6%). One of the MrgC agonists, BAM22, more than doubled the
      heat-induced cutaneous CGRP release from rat and mouse skin. The effect of BAM22,
      also known to activate opioid receptors, was further enhanced by combination with
      naloxone that had no effect on its own. This sensitizing effect proved to be
      independent of secondary prostaglandin formation, mast cell degranulation,
      protein kinase C (PKC) activation and independent of TRPV1. Nonetheless, the
      capsaicin-induced CGRP release was also sensitized. Receptive fields of 26
      mechano-heat sensitive C-fibers were treated with MrgC agonists. Only one unit
      was strongly and repeatedly excited and showed a profound sensitization to heat
      upon BAM22+naloxone. Two other established MrgC agonists (gamma2-melanocyte
      stimulating hormone and BAM8-22) were ineffective. Thus, BAM22 sensitizes the
      capsaicin- and heat-induced CGRP release in an apparently MrgC-unrelated way. The
      sensitization to heat appears unusually resistant against pharmacological
      interventions and does not involve TRPV1.

PMID- 18065156
TI  - Reticulospinal pathways in the ventrolateral funiculus with terminations in the
      cervical and lumbar enlargements of the adult rat spinal cord.
AB  - In the mammalian spinal cord, the ventrolateral funiculus (VLF) has been
      identified as critical to postural control and locomotor function, in part due to
      the reticulospinal pathways it contains. The primary purpose of this descriptive
      study was to investigate the distribution of neurons in the medulla labeled
      retrogradely from the VLF and the intermediate gray matter of specific lumbar and
      cervical spinal cord segments in the adult rat. We made discrete injections of
      Fluoro-Ruby (FR) into the intermediate gray matter at the cervical (C) 5/6, 7/8
      or lumbar (L) 2 segmental levels followed by a single injection of Fluoro-Gold
      (FG) into the right VLF at T9. Double-labeled medullary neurons were found
      primarily in the gigantocellular group of nuclei (Gi), distributed both
      ipsilaterally and contralaterally following cervical or lumbar FR injections. In
      addition, a substantial population of neurons contained within the vestibular
      group of nuclei was double labeled both ipsilaterally and contralaterally. We
      also identified a substantial population of Gi-related neurons located
      ipsilateral to the VLF injections that were double labeled following left
      unilateral FR injections at C5/6, C7/8 or L2. These results describe a
      substantial population of ipsilateral and commissural medullary neurons that
      project to both cervical and thoracolumbar segments. Two different populations of
      commissural neurons are described, one with axons that cross the midline rostral
      to T9, and one with axons that cross the midline caudal to T9. These observations
      provide strong additional evidence for a pattern of reticulo- and vestibulospinal
      projections that include substantial numbers of commissural neurons and project
      to multiple cervical and thoracolumbar levels.

PMID- 18065158
TI  - Metabotropic glutamate receptors subtype 5 are necessary for the enhancement of
      auditory evoked potentials in the lateral nucleus of the amygdala by tetanic
      stimulation of the auditory thalamus.
AB  - The lateral nucleus of the amygdala (LA) receives axonal projections from the
      auditory thalamus, the medial geniculate nucleus (MGN), and mediates auditory
      fear conditioning. Tetanic electrical stimulation of the MGN can induce long-term
      potentiation of acoustically-evoked responses (AEPs) recorded in the LA of
      anesthetized rats. The present study investigated the temporal development of
      tetanus-induced AEP potentiation recorded in the LA of anesthetized rats during
      the recording time up to 120 min after tetanization. In addition, the present
      study investigated whether the artificially-induced AEP potentiation is mediated
      by the metabotropic glutamate receptors subtype 5 (mGluR5). The results show that
      AEPs recorded in the LA to a broadband-noise burst were significantly enhanced
      immediately after tetanic but not low-frequency stimulation of the MGN. The AEP
      potentiation was well retained up to 120 min after tetanization. High-dose (1.5
      microg/4 microl) microinjection of the selective antagonist of mGluR5, 2-methyl-6
      (phenylethynyl)-pyridine (MPEP), into the ipsilateral lateral ventricle 30 min
      before tetanization completely blocked the AEP potentiation without affecting the
      baseline AEP. Low-dose (0.5 microg/4 microl) microinjection partially suppressed
      the AEP potentiation. When the high-dose MPEP was injected 40 min after
      tetanization, the AEP potentiation was not affected. These results indicate that
      in anesthetized rats mGluR5 receptors are necessary for the induction or early
      maintenance (40 min) of AEP potentiation in the LA by tetanic stimulation of the
      MGN.

PMID- 18065159
TI  - Periadolescent stress exposure exerts long-term effects on adult stress
      responding and expression of prefrontal dopamine receptors in male and female
      rats.
AB  - Recent research has demonstrated that experiential/environmental factors in early
      life can program the adult stress response in rats, and this is manifest as
      altered hypothalamic-pituitary-adrenocortical activity and behavior in response
      to a stressor. Very little work has been devoted to investigating whether the
      environment during adolescence plays a similar role in modulating ongoing
      developmental processes and how this might affect adult stress responding.
      Periadolescent predator odor (PPO) exposure was used here as a naturalistic model
      of repeated psychological stress. Behavioral and endocrine responses to PPO
      changed across the exposure period, and behavioral alterations persisted into
      adulthood. While adolescent rats showed pronounced avoidance responses upon
      initial PPO exposure, hyperactivity increased across the exposure period,
      especially in females. Corticosterone (cort) responses to stressor exposure also
      changed in females, with higher physiological baseline levels observed at the end
      of the exposure period. In adulthood, relative to rats who had received a control
      manipulation during adolescence, PPO-exposed rats were more fearful in a novel
      open field and displayed altered responses to a predator odor stress test in
      adulthood. Moreover, lower levels of the D2 dopamine (DA) receptor were measured
      in prefrontal (infralimbic and dorsopeduncular) cortices of PPO-exposed rats.
      These findings suggest that the adolescent period may represent a sensitive
      period during which developmental programming of the stress response occurs.

PMID- 18065160
TI  - Are the peptide sequences encrypted in food Chlorella protein a possible
      explanation for the immunostimulatory effects of microalgal supplements?

PMID- 18065161
TI  - Assessment of cocaine and other drug dependence in the general population:
      "gated" versus "ungated" approaches.
AB  - BACKGROUND: There is a need for large-scale epidemiological surveys to be (a)
      faithful to diagnostic specifications and (b) constrain time and participant
      burden associated with each section of a possibly lengthy interview. OBJECTIVE:
      To examine whether one "gating" approach devised for recent large-scale
      international psychiatric surveys results in a reduced number of identified cases
      of drug dependence and/or biases in estimated associations with background
      characteristics. DESIGN AND SETTING: Data from a recently released cross
      sectional, nationally representative household survey, the United States National
      Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were analysed.
      PARTICIPANTS: Forty-three thousand ninety-three English speaking adults aged 18
      years and over. MAIN OUTCOME MEASURES: Dependence upon cocaine and other illegal
      drug dependence, defined in two ways: "ungated" and "gated". "Ungated" dependence
      included all persons meeting criteria for DSM-IV dependence, without regard for
      DSM-IV drug abuse clinical features. "Gated" dependence required at least one
      feature of DSM-IV drug abuse. RESULTS: There was no statistically robust
      decrement in the estimated prevalence of cocaine or other drug dependence using a
      "gated" assessment. Patterns of association of cocaine dependence with background
      characteristics were not appreciably different when the gated and ungated
      approaches were applied. CONCLUSIONS: In panoramic mental health surveys, the
      inefficiency of an ungated approach must be balanced against the anticipated
      number of cases of dependence without associated social role impairments or harm.
      In this study, the reduction in the number of identified cocaine dependence cases
      appeared to be so small that even in a sample of over 40,000 participants,
      attenuation in population prevalence would prove difficult to detect.

PMID- 18065163
TI  - Test of measurement invariance of the FTND across demographic groups: assessment,
      effect size, and prediction of cessation.
AB  - BACKGROUND: Measurement non-invariance of the Fagerstrom test for nicotine
      dependence (FTND) across demographic groups could significantly bias group
      comparisons and screening for recruitment into treatment and genetic studies.
      Here clinically meaningful bias in the FTND across European-American and African
      American men and women was assessed by: (1) testing measurement invariance; (2)
      estimating effect sizes of non-invariance; and (3) assessing impact of adjusting
      for bias on the association between FTND and cessation. METHODS: European
      American and African-American current and former smokers (n=8301) were identified
      from a community-based telephone screening of 25,265 individuals from
      metropolitan Detroit, MI and St. Louis, MO. The FTND was administered to measure
      current dependence and lifetime dependence when smoking the most. Cessation was
      measured as having smoked 100 or more cigarettes but not smoked in the past 30
      days. RESULTS: Statistically significant measurement non-invariance for the FTND
      was found and more pronounced for lifetime than current dependence. However, the
      magnitude of effects appeared negligible. The largest variance in item response
      explained by measurement non-invariance was 3.1%. Adjusting for measurement non
      invariance made no difference in the associations between nicotine dependence and
      quitting smoking across groups. CONCLUSIONS: Although European-American and
      African-American men and women often report different scores on the FTND and have
      different response patterns to items on the FTND, it does not appear that such
      differences result from meaningful item-level measurement bias.

PMID- 18065164
TI  - Hyperactivity-inattention symptoms in childhood and substance use in adolescence:
      the youth gazel cohort.
AB  - BACKGROUND: This study addresses in both genders the relationship between
      childhood Hyperactivity-inattention symptoms and subsequent adolescent substance
      use, while controlling for psychiatric comorbidity, temperament and environmental
      risk factors. METHODS: 916 subjects (421 males, 495 females) aged 7-18 were
      recruited from the general population and surveyed in 1991 and 1999. Child
      psychopathology and substance use patterns were evaluated through parent and
      adolescent self-reports. Multivariate modeling was performed to assess the
      effects of childhood Hyperactivity-inattention symptoms and other risk factors on
      adolescent substance use. RESULTS: In males, Hyperactivity-inattention symptoms
      alone accounted for the risk of subsequent regular cannabis smoking (OR=3.14,
      p=0.03) and subsequent lifetime use of other drugs including stimulants, opiates,
      inhalants and sedatives (OR=2.72, p=0.02). In females, Hyperactivity-inattention
      symptoms did not independently increase the liability to later substance use. In
      males, the temperament trait activity was a significant predictor of subsequent
      regular cannabis smoking (OR=2.32, p=0.04). CONCLUSIONS: This survey points to a
      possible specific link between Hyperactivity-inattention symptoms and subsequent
      cannabis use and experimentation of harder drugs in males.

PMID- 18065162
TI  - Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse
      and cocaine-enhanced nucleus accumbens dopamine in rats.
AB  - Gabapentin is a gamma-aminobutyric acid (GABA) analogue, with GABAmimetic
      pharmacological properties. Gabapentin is used for the treatment of seizures,
      anxiety and neuropathic pain. It has been proposed that gabapentin may be useful
      in the treatment of cocaine dependence. However, clinical trials with gabapentin
      have shown conflicting results, while preclinical studies are sparse. In the
      present study, we investigated the effects of gabapentin on intravenous cocaine
      self-administration and cocaine-triggered reinstatement of drug-seeking behavior,
      as well as on cocaine-enhanced dopamine (DA) in the nucleus accumbens (NAc). We
      found that gabapentin (25-200 mg/kg, i.p., 30 min or 2 h prior to cocaine) failed
      to inhibit intravenous cocaine (0.5 mg/kg/infusion) self-administration under a
      fixed-ratio reinforcement schedule or cocaine-triggered reinstatement of cocaine
      seeking behavior. In vivo microdialysis showed that the same doses of gabapentin
      produced a modest increase (approximately 50%, p<0.05) in extracellular NAc GABA
      levels, but failed to alter either basal or cocaine-enhanced NAc DA. These data
      suggest that gabapentin is a weak GABA-mimic drug. At the doses tested, it has no
      effect in the addiction-related animal behavioral models here tested. This is in
      striking contrast to positive findings in the same animal models shown by another
      GABAmimetic--gamma-vinyl GABA (see companion piece to present article).

PMID- 18065166
TI  - The complete mitochondrial genome of the tobacco hornworm, Manduca sexta,
      (Insecta: Lepidoptera: Sphingidae), and an examination of mitochondrial gene
      variability within butterflies and moths.
AB  - The entire mitochondrial genome of the tobacco hornworm, Manduca sexta
      (Lepidoptera: Spinghidae) was sequenced -- a circular molecular 15516 bp in size.
      The arrangement of the protein coding genes (PCGs) was the same as that found in
      the ancestral insect, however Manduca possessed the derived tRNA arrangement of
      CR-M-I-Q which has been found in all Lepidoptera sequenced to date. Additionally,
      Manduca, like all lepidopteran mt genomes, has numerous large intergenic spacer
      regions and microsatellite-like repeat regions. Nucleotide composition is highly
      A+T biased, and the lepidopterans have the second most biased nucleotide
      composition of the insect orders after Hymenoptera. Secondary structural features
      of the PCGs identified in other Lepidoptera were present but highly modified by
      the presence of microsatellite-like repeat regions which may significantly alter
      their function in the post-transcriptional modification of pre-mRNAs. Secondary
      structure models of the ribosomal RNA genes of Manduca are presented and are
      similar to those proposed for other insect orders. Conserved regions were
      identified within non-translated spacer regions which correspond to sites for the
      origin and termination of replication and transcription. Comparisons of gene
      variability across the order suggest that the mitochondrial genes most frequently
      used in phylogenetic analysis of the Lepidoptera, cox1 and cox2, are amongst the
      least variable genes in the genome and phylogenetic resolution could be improved
      by using alternative, higher variability genes such as nad2, nad3, nad4 and nad5.

PMID- 18065167
TI  - Sex versus parthenogenesis: a transcriptomic approach of photoperiod response in
      the model aphid Acyrthosiphon pisum (Hemiptera: Aphididae).
AB  - Most aphids develop a cyclic parthenogenesis life-cycle. After several
      generations of viviparous parthenogenetic females, it follows a single annual
      generation of sexual individuals, usually in autumn, that mate and lay the sexual
      eggs. Shortening of photoperiod at the end of the summer is a key factor inducing
      the sexual response. With the survey here reported we aimed at identifying a
      collection of candidate genes to participate at some point in the cascade of
      events that lead to the sexual phenotypes. Following a suppression subtractive
      hybridization methodology (SSH) on the model aphid Acyrthosiphon pisum, we built
      and characterised two reciprocal cDNA libraries (SDU and SDD) enriched
      respectively in genes up-regulated or down-regulated by short photoperiod
      conditions that lead to the sexual response in this aphid species. A total of 557
      ESTs were obtained altogether representing 223 non-overlapping contigs. 29% of
      these were new sequences not present in previous aphid EST libraries. BLAST
      searches allowed putative identification of about 54% of the contigs present in
      both libraries. Relative quantification of expression through real-time
      quantitative PCR demonstrated the differential expression in relation with the
      photoperiod of 6 genes (3 up-regulated and 3 down-regulated by shortening the day
      length). Among these, expression of a tubulin gene, two cuticular proteins and a
      yet unidentified sequence along the day-night cycle was further investigated.
      Implications for current studies on gene regulation of the dichotomy sex vs.
      parthenogenesis in aphids are discussed.

PMID- 18065165
TI  - The effects of HIV on P300 are moderated by familial risk for substance
      dependence: implications for a theory of brain reserve.
AB  - BACKGROUND: The goal of the study was to test the validity of additive versus
      synergistic versus underadditive versions of brain reserve theory within the
      context of HIV/AIDS. In addition, it tested the convergent validity of 2
      operational definitions of premorbid reserve: verbal IQ (VIQ) and a family
      history (FH) of substance abuse or dependence. METHODS: Seventy HIV-1
      seronegative and 115 HIV-1 seropositive male and female volunteers were assigned
      to 4 subgroups defined by the crossing of a VIQ score < versus > or = 90 with the
      presence versus absence of a paternal history of alcohol, cocaine, or opiate
      abuse or dependence. The principal dependent measure was the P300 event related
      brain potential elicited during the Stroop color-word interference task. RESULTS:
      The principal finding was an underadditive effect of FH plus HIV/AIDS on P300
      area over the frontal region: FH reduced frontal scalp P300 to such a degree that
      the additional effects of HIV/AIDS were blunted. The alternate operational
      definition of brain reserve, VIQ, had no effect on P300 and did not alter the
      effects of HIV/AIDS. CONCLUSIONS: Familial risk for substance dependence and low
      VIQ compromise different aspects of brain structure and/or function and therefore
      differ in their relationship to HIV/AIDS and P300. Genetic differences associated
      with familial risk may reduce brain reserve to such a degree that the
      neurophysiological effects of HIV/AIDS can no longer be measured.

PMID- 18065168
TI  - ISApl1, a novel insertion element of Actinobacillus pleuropneumoniae, prevents
      ApxIV-based serological detection of serotype 7 strain AP76.
AB  - Actinobacillus pleuropneumoniae, a gram-negative rod of the Pasteurellaceae
      family, causes pleuropneumonia in pigs. Establishing A. pleuropneumoniae free
      herds is difficult due to the occurrence of persistently infected animals. The
      ApxIV toxin is expressed by A. pleuropneumoniae in vivo and an ELISA based on the
      toxin is used to detect infection and to differentiate between infected and
      vaccinated animals. In this study, we have identified a 1070bp insertion element
      of the IS30 family, designated ISApl1, in the A. pleuropneumoniae serotype 7
      strain AP76. ISApl1 contains a 924bp ORF encoding a transposase, which is flanked
      by 27bp inverted repeats showing six mismatches. We investigated the occurrence
      of ISApl1 in other A. pleuropneumoniae strains, and its possible interference
      with virulence associated factors. Four insertion sites were identified in AP76:
      within the apxIVA toxin ORF, within a putative autotransporter adhesin ORF,
      upstream of a capsular polysaccharide biosynthesis gene cluster, and downstream
      of a beta-lactamase gene. ISApl1 is also present in some serotype 7 field
      isolates, but not in reference or field strains of other serotypes. In A.
      pleuropneumoniae AP76, the transposase gene is transcribed in vitro. The
      insertion in the apxIVA toxin gene remains stable after animal passage. Since
      this insertion should disrupt toxin expression, we tested 7 pigs infected with
      AP76 at day 21 post-infection. All were negative in the ApxIV ELISA but four out
      of seven were positive in an ApxII toxin ELISA. These results show that insertion
      elements can affect the detection of A. pleuropneumoniae infected animals.

PMID- 18065169
TI  - Serial changes in urinary cadmium concentrations and degree of renal tubular
      injury after soil replacement in cadmium-polluted rice paddies.
AB  - Targeting persons requiring observation in the Cd-polluted Kakehashi River basin
      a serial observation study was conducted. Namely we followed the serial changes
      in 50 subjects who ingested household rice for 10 years after replacement of Cd
      polluted soil in rice paddies. The serial changes in urinary substance levels in
      individuals were determined adjusting for the potential effect of age using a
      general linear mixed model. Cd excretions decreased with increasing number of
      years elapsed, with the partial regression coefficients of the number of years
      elapsed statistically significant in the women. The ratio of the Cd excretion
      theoretical values at the completion of soil replacement and 10 years later was
      0.60 and the reduction rate was calculated as 5.0% per year in women. However, it
      was surmised that in practice a decrease to the level of inhabitants of non
      polluted districts would not be achievable. The indices of renal tubular injury
      (beta(2)-microglobulin, retinol binding protein (RBP), total protein, amino-N and
      glucose) with the exception of amino-N in men showed increased excretion in both
      sexes with increasing number of years elapsed with statistically significant
      differences in RBP and total protein in both sexes and glucose in men. In this
      study using a general linear mixed model, which is an appropriate statistical
      method to perform a follow-up study, Cd concentrations in rice and urine were
      found to decrease after Cd exposure was reduced, but the degree of renal tubular
      injury was not found to improve, leading to the conclusion that the renal tubular
      injury induced by environmental Cd exposure is irreversible.

PMID- 18065170
TI  - A comparison between freezing methods for the cryopreservation of stallion
      spermatozoa.
AB  - The effects of sperm freezing concentration (40 x 10(6)mL(-1) vs. 400 x 10(6)mL(
      1)), straw size (0.25 mL vs. 0.5 mL) and freezing method (liquid nitrogen vapour
      in a Styrofoam box vs. programmable freezing machine) were evaluated in a 2 x 2 x
      2 factorial experimental design using 3 split ejaculates from each of 4
      stallions. Immediately after thawing, the total motility and forward progressive
      motility of spermatozoa frozen at a concentration of 40 x 10(6)mL(-1) was higher
      than for spermatozoa frozen at 400 x 10(6)mL(-1). No significant differences were
      observed in the semen parameters assessed after cryopreservation in either 0.25
      or 0.5 mL straws. However, the programmable freezer provided a more consistent
      and reliable freezing rate than liquid nitrogen vapour. We conclude that an
      effective protocol for the cryopreservation of stallion spermatozoa at low
      concentrations would include concentrations of 40 x 10(6)mL(-1) in 0.25 mL straws
      using a programmable freezer. This freezing protocol would be suitable for
      emerging sperm technologies such as sex-preselection of stallion spermatozoa as
      the sorting process yields only low numbers of spermatozoa in a small volume
      available for either immediate insemination or cryopreservation.

PMID- 18065171
TI  - Development of a new photocrosslinkable biodegradable bioadhesive.
AB  - Adhesives provide a needle-free method of wound closure and do not require local
      anaesthetics. Polymeric adhesives have been used for about 3 decades for joining
      several tissues of the organism. Also, they can accomplish other tasks, such as
      haemostasis and the ability to seal air leakages and have the potential to serve
      as delivery systems. PCL was modified with 2-isocyanatoethylmethacrylate to form
      a macromer that was crosslinked via UV irradiation using Irgacure 2959 by CIBA as
      the photoinitiating agent. The characterization of the materials was accomplished
      by: attenuated total reflectance-Fourier transform infrared (ATR-FTIR), swelling
      capacity determination, evaluation of adhesive capacity (by reaction with
      aminated substrates) and determination of surface energy by contact angle
      measurement. Thermal characterization of the adhesive was performed by dynamical
      mechanical thermal analysis (DMTA) and thermogravimetric analysis (TGA). The
      morphology of PCL networks was observed using scanning electron microscopy (SEM)
      both after crosslinking process and following biodegradation in human plasma. The
      haemocompatibility of the membranes was also evaluated by thrombosis and
      haemolysis tests.

PMID- 18065172
TI  - Improved transfection efficiency of CS/DNA complex by co-transfected chitosanase
      gene.
AB  - Previously, we had demonstrated that insufficient intracellular unpacking of
      exogene from its chitosan carrier contributes towards the restricted transfection
      efficiency of CS/DNA complex. In order to enhance intracellular unpacking and
      thus improve the transfection efficiency, our present work has addressed a novel
      strategy of chitosanase gene (csn) co-transfection. An Aspergillus fumigatuscsn
      gene was semi-synthesized and cloned into a prokaryotic expression vector,
      plasmid pGEX-3X, meanwhile a mutant csn gene encoding an inactive Asp129-Asn
      chitosanase was generated by site-directed mutagenesis. Both active csn (acCSN)
      and inactive csn (inCSN) genes were expressed in bacteria cells and chitosan
      degradation activities of those purified recombinant proteins were tested. These
      csn genes were further subcloned into an eukaryotic expression vector, plasmid
      pTracer-CMV/Bsd, containing a gfp reporter gene. Recombinant plasmid pTracer
      accsn or pTracer-incsn was co-transfected with plasmid pTracer/Bsd/LacZ, which
      contains an additional lacZ reporter gene, into C2C12 myoblast cells by CS/DNA
      complex. The expression of gfp reporter gene was determined by fluorescence
      microscope, while the expression of lacZ reporter was evaluated quantitatively by
      beta-galactosidase activity. All together, findings indicate that during the
      exogene being delivered into mammalian cells by CS/DNA complex, the csn co
      transfection is beneficial for the exogene expression.

PMID- 18065173
TI  - Comparison between lipolysis and compendial dissolution as alternative techniques
      for the in vitro characterization of alpha-tocopherol self-emulsified drug
      delivery systems (SEDDS).
AB  - In vitro characterization of alpha-tocopherol SEDDS formulations was performed by
      (1) lipolysis in bio-relevant media, and (2) physical assessment by dissolution,
      particle size, and turbidity analyses. Both methods were statistically correlated
      using a 25-run, five-factor multiple-level d-optimal mixture design. Independent
      variables were SEDDS composition [vitamin E (12.5-25%), Tween 80 (10-40%),
      labrasol (0-10%), alcohol (0-10%), and captex 355 (20-50%)]. Measured responses
      were percent lipolysis, percent vitamin E retained in the aqueous layer of the
      digestion medium, and percent vitamin E dissolved in the dissolution medium.
      Percent lipolysis ranged from 0% to 66.3%. Percent vitamin E retrieved in the
      aqueous layer of the digestion and dissolution media ranged from 3% to 29.3% and
      from 25.9% to 101.7%, respectively. Turbidity ranged from 28 to 403JTU and the
      average droplet size was >1.0 microm. All formulation ingredients had significant
      (p<0.05) effect on percent lipolysis. Only two factors, Tween and vitamin E had
      significant effect on vitamin retention in the aqueous layer post-lipolysis.
      Tween, labrasol, and captex 355 had significant effect on vitamin E dissolution.
      Poor correlation was observed between the responses. Formulation ingredients
      influenced each response differently; and therefore, each method can only reveal
      distinctive characteristics of the SEDDS formulation and may not be used
      interchangeably.

PMID- 18065174
TI  - Determination of intraliposomal pH and its effect on membrane partitioning and
      passive loading of a hydrophobic camptothecin, DB-67.
AB  - The purpose of this work was to study the effect of pH on the liposomal
      encapsulation of a model camptothecin anti-tumor agent, DB-67, by considering the
      state of ionization and bilayer membrane/water partitioning of the drug as a
      function of pH. A novel fluorescence method was developed to monitor
      intravesicular pH in liposomal formulations containing entrapped DB-67 by using
      the drug itself as a pH indicator. Fluorescence spectra were recorded in aqueous
      buffers and liposomes and used to estimate the ionization constant of the A-ring
      phenol of DB-67 (pKappa(a2)) and shifts in ionization constants ( pKappa (a1) and
      pKappa(a2) ) due to membrane binding. Bilayer/water partitioning studies by
      equilibrium dialysis were employed to show that DB-67 is highly membrane bound
      over the entire pH range examined though binding decreases with an increase in
      pH. The observed ionization constants of membrane-bound DB-67 obtained from the
      equilibrium dialysis experiments were consistent with observations from
      fluorescence measurements and previous permeability results. The pH dependence of
      DB-67 loading using a passive loading technique was found to reflect the pH
      dependence of membrane binding of the drug. This results in poor encapsulation
      efficiency of DB-67 at high pH, necessitating further development of formulation
      strategies to improve loading efficiency.

PMID- 18065175
TI  - The in vitro anti-plasmodial and in vivo anti-malarial efficacy of combinations
      of some medicinal plants used traditionally for treatment of malaria by the Meru
      community in Kenya.
AB  - The use of herbal drugs as combinations has existed for centuries in several
      cultural systems. However, the safety and efficacy of such combinations have not
      been validated. In this study, the toxicity, anti-plasmodial and antimalarial
      efficacy of several herbal drug combinations were investigated. Lannea
      schweinfurthii, Turraea robusta and Sclerocarya birrea, used by traditional
      health practitioners in Meru community, were tested for in vitro anti-plasmodial
      and in vivo anti-malarial activity singly against Plasmodium falciparum and
      Plasmodium berghei, respectively. Methanolic extract of Turraea robusta was the
      most active against Plasmodium falciparum D6 strain. Aqueous extracts of Lannea
      schweinfurthii had the highest anti-plamodial activity followed by Turraea
      robusta and Sclerocarya birrea. D6 was more sensitive to the plant extracts than
      W2 strain. Lannea schweinfurthii extracts had the highest anti-malarial activity
      in mice followed by Turraea robusta and Sclerocarya birrea with the methanol
      extracts being more active than aqueous ones. Combinations of aqueous extracts of
      the three plants and two others (Boscia salicifolia and Rhus natalensis)
      previously shown to exhibit anti-plasmodial and anti-malarial activity singly
      were tested in mice. Marked synergy and additive interactions were observed when
      combinations of the drugs were assayed in vitro. Different combinations of
      Turraea robusta and Lannea schweinfurthii exhibited good in vitro synergistic
      interactions. Combinations of Boscia salicifolia and Sclerocarya birrea; Rhus
      natalensis and Turraea robusta; Rhus natalensis and Boscia salicifolia; Turraea
      robusta and Sclerocarya birrea; and Lannea schweinfurthii and Boscia salicifolia
      exhibited high malaria parasite suppression (chemo-suppression >90%) in vivo when
      tested in mice. The findings are a preliminary demonstration of the usefulness of
      combining several plants in herbal drugs, as a normal practice of traditional
      health practitioners.

PMID- 18065177
TI  - [An update on Candida dubliniensis].
AB  - Eleven years ago, Irish authors, using molecular biology, demonstrated the
      existence of Candida dubliniensis, a new species of Candida close to Candida
      albicans. Initially isolated from AIDS patients with oral candidiasis, this
      species was detected, even in immunocompetent patients. Recently, with new, easy
      to implement identification tests (latex, immunochromatography), numerous
      epidemiological studies were undertaken. In most studies, C. dubliniensis was
      most often identified in the oral cavity. In the absence of HIV infection, the
      proportion C. dubliniensis/C. albicans ranged from 1 to 5% but it increased to 15
      20% in case of HIV infection. It should be stressed that, from an experimental
      point of view, the acquisition of a secondary resistance to fluconazole is more
      quickly obtained with C. dubliniensis that with C. albicans, this resistance
      remains exceptionally observed in clinical observations.

PMID- 18065176
TI  - Early onset West syndrome with cerebral hypomyelination and reduced cerebral
      white matter.
AB  - Numerous numbers of pre-, peri- and postnatal damages cause West syndrome in
      early infancy, however, etiology in many cases are not still elucidated despite
      intensive biochemical and neuroradiologic investigations. We described four
      patients having early onset epileptic encephalopathy with severe hypomyelination
      and reduction in cerebral white matter. The clinical symptoms of these patients
      are impaired visual attention, acquired microcephaly, spastic tetraplegia,
      profound psychomotor delay and infantile spasms since early infancy. All patients
      had striking hypomyelination of cerebrum, reduced volume of white matter and
      cortical atrophy on MRI. Serial MRI investigations in three patients showed
      absence of myelination of the white matter. On EEG, one patient revealed
      suppression-burst and other three had hypsarrhythmia. Despite having intractable
      seizures, no patient showed deterioration of neurological development. The group
      of these findings is mimicking to clinical manifestations of 3-phosphoglycerate
      dehydrogenase deficiency, and has some overlap with progressive encephalopathy
      with edema, hypsarrhythmia, and optic atrophy (PEHO) like syndrome, however it is
      not compatible with these two conditions. The findings observed in our patients
      can be regarded as a new clinical condition associated with early onset West
      syndrome.

PMID- 18065178
TI  - [Is there an excess of AIDS-related mortality in Aquitaine? Data collected
      through the French mandatory reporting system, 1982-2005].
AB  - OBJECTIVES: The mortality rate among AIDS patients reported through the French
      mandatory reporting system since 1982 is particularly high in Aquitaine, a south
      west area of France. This study was made to confirm that mortality was higher in
      Aquitaine patients than in the rest of France, and to determine its causes.
      DESIGN: All the cases reported between January 1982 and June 2005 were included.
      Cox's proportional hazard models were used to determine the relative risk (RR) of
      death among patients living in Aquitaine. Two periods were considered to take
      into account the introduction of highly active antiretroviral therapy (HAART) in
      1996. RESULTS: Since 1982, 60,212 AIDS patients were reported. After adjustment
      on the main patient features, the risk of death was significantly higher in AIDS
      patients living in Aquitaine than in other regions (RR=1.12; IC95%=[1.06-1.18])
      before the introduction of HAART. After 1996, this difference did not persist,
      and an opposite trend was even observed (RR=0.90; IC95%=[0.75-1.09]).
      CONCLUSIONS: The higher overall mortality rate in Aquitaine was due to a higher
      risk of death in that area before 1996. Several hypotheses can explain this
      result, such as a less exhaustive notification, or different characteristics of
      the subjects. The opposite trend that was observed after the introduction of
      HAART will have to be checked in the next few years.

PMID- 18065179
TI  - [Assessing the application of Rwanda's national protocol for uncomplicated
      malaria treatment in healthcare institutions in Kigali City, Rwanda].
AB  - In November 2001, the National Health Ministry of Rwanda advocated a new
      therapeutic protocol replacing chloroquine by an amodiaquine+sulfadoxine
      pyrimethamine combination for the treatment of uncomplicated malaria. OBJECTIVES:
      This study had for aim to assess the application of this new protocol in Kigali
      healthcare institutions. POPULATION AND METHODS: A knowledge, attitudes and
      practices study (KAP) was carried out between June and August 2003. A
      questionnaire was answered by 120 care providers working in 15 healthcare
      institutions selected randomly in health facilities treating uncomplicated
      malaria. Antimalarial treatments prescribed to 150 patients were also reviewed
      from consultation files and analyzed. RESULTS: After analysis, 63.3%
      prescriptions were in line with the national protocol. Factors associated to the
      nonobservance of the national protocol were: the carer's ignorance of any
      recommended treatment, his doubt of efficacy of recommended drugs, and his fear
      of adverse effects. CONCLUSIONS: The authors recommend informing the care
      providers about the national protocol. Findings also demonstrate the need to
      include care providers in any modifications of the national policy in terms of
      drug efficacy and potential adverse effects of the new strategy.

PMID- 18065180
TI  - [Epidemiology and susceptibility profile of blood culture isolates in an
      intensive care unit (2002-2005)].
AB  - INTRODUCTION: The aim of our study was to determine the epidemiological profile
      and the antibiotics susceptibility of bacteria identified in blood culture in the
      intensive care unit, to improve empirical antibiotherapy. MATERIAL AND METHOD: A
      retrospective study was made over a four-year period (2002-2005) in the intensive
      care unit of the Mohammed-V Military Hospital. It included all the bacteria
      identified in blood culture. RESULTS: During this period, we collected 286
      isolates, Gram-negative bacilli 49.3% and Gram-positive cocci 46.85%. The most
      frequently identified species were Acinetobacter baumannii (13.63%),
      Staphylococcus epidermidis (12.6%), Staphylococcus aureus (11.9%), and
      Pseudomonas aeruginosa (7%). Enterobacteriaceae accounted for 25.54%: Klebsiella
      pneumoniae 7%, and Enterobacter cloacae 7%. The rate of methicillin-resistant
      Staphylococcus aureus was 52.94 % and coagulase negative staphylococci 60.24%. No
      resistance to glycopeptides was observed. Enterobacteriaceae were resistant to
      third generation cephalosporins in 42.6 % and had a broad-spectrum betalactamase
      phenotype in 18%. The resistance rate of A. baumannii was 68.7% for ceftazidime
      and 31.4% for imipenem. The resistance rate of P. aeruginosa to the third
      generation cephalosporines and the imipenem were respectively 16.6% and 10.5%.
      CONCLUSION: A regular epidemiologic study of blood culture isolates and
      determination of susceptibility to antibiotics are necessary to improve empiric
      therapy.

PMID- 18065181
TI  - [What kind of clinical, epidemiological, and biological data is essential for the
      diagnosis of Lyme borreliosis? Dermatological and ophtalmological courses of Lyme
      borreliosis].
AB  - Lyme borreliosis (BL) is a multisystem infectious tick-transmitted disease. The
      diversity of Borrelia burgdorferi is the reason for a wide spectrum of
      dermatological and ophthalmologic presentations between patients from Europe and
      from other countries. In Europe, the main manifestations are dermatological.
      During the early stage, the diagnosis is clinical: finding erythema migrans (EM)
      a few days after a tick bite is sufficient; several EM mean an early-disseminated
      disease. Borrelial lymphocytoma (only in Europe) is a solitary nodule or plaque
      (earlobe, nipple, scrotum), which appears during the second stage. The diagnosis
      relies on clinical and histological findings (B-cell infiltration) and a positive
      serological test. It is sometimes difficult to make the difference between BL and
      B-cell lymphoma and pseudo lymphoma; an empirical antibiotic trial period will be
      helpful for the diagnosis in this case. During the late stage, the clinical
      evolution of acrodermatitis chronica atrophicans is progressive: inflammatory
      then atrophic lesions appear, often on the hands, limbs, or feet. The diagnosis
      is made on histological findings (T-cell infiltration) and a positive serological
      test. The relationship between BL and morphea or lichen sclerosus was not
      demonstrated according to the latest reports. Ocular manifestations are rare
      events occurring during every stage of the disease. A wide spectrum of
      presentations is possible (uveitis and optic neuritis). BL is responsible for
      ocular infection or inflammation. A neurological presentation is often associated
      with the ocular manifestation. Proving the diagnosis is often difficult because
      of these polymorphous manifestations.

PMID- 18065182
TI  - Deletion of the lifespan determinant p66(Shc) improves performance in a spatial
      memory task, decreases levels of oxidative stress markers in the hippocampus and
      increases levels of the neurotrophin BDNF in adult mice.
AB  - Deletion of the p66(Shc) gene in mice results in reduced levels of oxidative
      stress and longer lifespan. Reactive oxygen species (ROS) can lead to tissue
      damage, particularly in the brain. In this study we extended previous findings on
      the behavioral phenotype of the p66(Shc-/-) mice. Cognitive performance of adult
      and old p66(Shc-/-) and p66(Shc+/+) mice was tested in a Morris water maze (MWM)
      task while general reactivity and pain sensitivity were assayed at adulthood,
      respectively, in an open field and by means of a tail flick test. Levels of brain
      derived neurotrophic factor (BDNF), a neurotrophin involved in several aspects of
      synaptic plasticity, emotionality and pain sensitivity, were assessed in selected
      brain areas. P66(Shc-/-) adult subjects, compared to WT, overall showed a better
      performance in the MWM, lower emotionality and a higher pain threshold, in
      addition to increased basal levels of BDNF in the hippocampus, as well as
      decreased levels of oxidative stress markers in the same brain area. Although all
      aged subjects failed to learn the cognitive task, aged p66(Shc-/-) mice were
      characterized by a better physical performance. These results suggest an
      interaction between the p66(Shc) gene and specific signaling pathways involved in
      behavioral adaptation to stress and aging.

PMID- 18065183
TI  - Simultaneous analysis of flavonoids from Hypericum japonicum Thunb.ex Murray
      (Hypericaceae) by HPLC-DAD-ESI/MS.
AB  - A novel and sensitive HPLC-UV method has been developed for the simultaneous
      determination of five major flavonoids in Hypericum japonicum hydroalcoholic
      extract. The chemical profile of five flavonoids, including taxfolin-7-O-alpha-L
      rhamnoside (1), isoquercitrin (2), quercitrin (3), quercetin-7-O-alpha-L
      rhamnoside (4) and quercetin (5) was acquired by using high-performance liquid
      chromatography-diode array detector coupled to an electrospray tandem mass
      spectrometer (HPLC-DAD-ESI/MS). The analysis was performed on a ZORBAX SB-C18
      analytical column (5 microm, 250 mm x 4.6 mm, i.d.) with a gradient solvent
      system of acetonitrile-0.5% aqueous formic acid. The validation was carried out
      and the linearities (r(2)>0.9997) and recoveries (ranged from 98.4% to 99.8%)
      were acceptable. The limits of detection (LOD) of these flavonoids ranged from
      0.5 to 7.5 ng. The results indicated that the contents of investigated flavonoids
      in H. japonicum varied significantly from habitat to habitat with contents
      ranging from 2.00 to 34.18 mg/g. The proposed method is simple, effective and
      suitable for the quality control of this traditional Chinese medicine (TCM).

PMID- 18065184
TI  - Pediatric fever and leg pain.

PMID- 18065185
TI  - The impact of routine cognitive screening by using the clock drawing task in the
      evaluation of elderly patients in the emergency department.
AB  - The prevalence of cognitive impairment, as reflected by failure to correctly
      perform a clock drawing task, in elderly Emergency Department (ED) patients was
      assessed. Additionally, we evaluated whether primary care provider notification
      of cognitive impairment spurred further cognitive evaluation. The clock drawing
      task was administered to a convenience sample of 100 elderly, English-speaking
      subjects presenting for reasons other than altered mentation at a community
      hospital ED. Primary care providers were contacted regarding abnormal clock
      drawing task results immediately and again after 2 months to determine if there
      was further evaluation of cognition. Of the 100 subjects enrolled, 30% were
      unable to correctly complete the clock drawing task, but only 8 had further
      evaluation of their cognitive abilities, resulting in four new diagnoses of
      dementia. Subjects who drew incorrect clocks (54%; 16/30) were more likely to be
      reevaluated in the ED within 2 months than those who drew correct clocks (29%;
      20/70; p < 0.02). Cognitive screening of elderly ED patients with the clock
      drawing task identified a substantial number with unsuspected abnormal cognition.
      Further evaluation by their primary care physicians in follow-up was
      disappointing.

PMID- 18065186
TI  - Cardiac tamponade via a fistula to the pericardium from a hydatid cyst: case
      report and review of the literature.
AB  - Although echinococcus is endemic in many sheep-raising areas of the world,
      cardiac involvement is rare. Cysts usually reach the heart by means of the
      coronary circulation, but other routes have been proposed. Pericardial tamponade
      due to a hydatid cyst has not yet been described in the literature. We present
      the case of a 46-year-old woman who presented to the Emergency Department with
      complaints of chest pain and mild dyspnea. Her medical history was positive for a
      liver hydatid cyst operation 26 years earlier. She was tachypneic, tachycardic,
      and hypotensive. Pleural and pericardial effusions were detected on transthoracic
      echocardiography. When she worsened clinically, pericardiocentesis was performed
      and she promptly improved. A fistula was detected between the liver and
      pericardium on computed tomography (CT) scan of the torso. Serologic test
      (agglutination) for Echinococcus granulosus was positive in a 1/32 dilution. A
      final diagnosis of mediastinal hydatic cyst was made, and a 4-week course of
      albendazol was given. Then the cyst was surgically excised, and the patient
      recovered without complications.

PMID- 18065187
TI  - Evidence from a cohort of able bodied adults to support the need for driver
      training for motorized scooters before community participation.
AB  - OBJECTIVE: This study sought to utilize the implementation of a new competency
      test in order to define skills required to safely drive a motorized scooter. This
      test endeavours to reduce the number of driving and pedestrian related accidents,
      by determining an acceptable level of driver skill and awareness. METHODS:
      Healthy subjects, who might at some time use a motorized scooter for mobility,
      were recruited from the local community. Each undertook a driver competency test
      including basic driving skills, traffic and multiple tasks. Ten subjects repeated
      the test three times to determine practice effect on proficiency. RESULTS: Thirty
      three of the 50 participating subjects (mean age 34 years) failed at least one
      test item. Basic skills of reversing, weave and zigzag, and all traffic and
      performing multiple simultaneous tasks produced failures. CONCLUSION: Driving
      skills for motorized scooters need to be taught and learned with assessment for
      competency recommended before unrestricted community driving is allowed. PRACTICE
      IMPLICATIONS: Basic driving skills including weaving, steering in reverse and
      traffic and multiple tasking need to be taught and tested for all new users of
      this equipment.

PMID- 18065188
TI  - Telling "the truth" in dementia--do attitude and approach of general
      practitioners and specialists differ?
AB  - OBJECTIVE: The prevailing opinion in the literature that disclosing the diagnosis
      of dementia to patients is important is not always put into practice. The purpose
      of this study was to investigate differences between GPs and specialists
      (neurologists and psychiatrists) in the German ambulatory care system concerning
      the disclosure of the diagnosis of dementia. METHODS: Thirty in depth interviews
      with randomly selected GPs were conducted. On this basis a standardised
      questionnaire was developed and sent to 389 GPs and 239 neurologists and
      psychiatrists. RESULTS: The postal survey revealed only minor differences between
      GPs and specialists, both groups being equally in favour of a timely disclosure.
      For example, 70% of the GPs and 77% of the specialists strongly agreed that
      "patients with dementia should be informed early because of the possibility to
      plan their lives". This positive attitude is pronounced among younger physicians,
      but is somewhat contradicted by difficulties in the communication with patients
      expressed in the interviews. In the interviews, what may be described as a
      "double taboo" emerges, in that GPs describe taboo topic areas related to
      dementia for them and for their patients. CONCLUSION: The postal survey shows the
      two professional groups to be very much in favour of a timely disclosure--an
      attitude that is pronounced among younger physicians. These findings can be
      interpreted as a recent change of attitudes regarding the disclosure of the
      diagnosis of dementia in the medical profession. PRACTICE IMPLICATIONS: Training
      opportunities are needed in order to overcome communication obstacles in the
      doctor-patient-communication about dementia.

PMID- 18065189
TI  - [Exacerbation in asthma: definitions and immunopathology].
AB  - There is no unequivocal definition of exacerbation in asthma. These are defined
      as episodes of increased or aggravated respiratory symptoms or as use of oral
      corticosteroid therapy. Viral infection is the most frequent cause of
      exacerbations. Inflammation during exacerbations is heterogeneous. It may be
      associated with bronchial hypereosinophilia, which is used as a predictive marker
      for exacerbation, and with neutrophilia, which is more resistant to
      corticosteroids. During viral infection, an inappropriate Th1 antiviral
      inflammation develops, associated with the intrinsic Th2 activity that leads to
      an aberrant immune response. Exacerbations secondary to allergen exposure are
      classically described as due to a Th2-type inflammation; but Th1 response also
      seems to play a role. Exposure to air pollutants appears able not only to induce
      bronchial inflammation but also to potentiate the inflammatory reactions of
      patients with exacerbations.

PMID- 18065190
TI  - [Ten-year morbidity and mortality in a cohort of dyslipidemic patients seen at a
      hospital endocrinology department].
AB  - OBJECTIVE: To describe the cardiovascular morbidity and mortality and associated
      risk factors of a population of patients with dyslipidemia seen ten years earlier
      for a cardiovascular risk assessment in the endocrinology department of a French
      hospital. METHODS: Patients seen for a cardiovascular risk assessment between
      1988 and 1992 were re-examined in the department, or contacted by mail or their
      vital status (and cause of death, if any) was obtained from the INSERM Cepi-Dc
      database. RESULTS: Vital status was available for 89.7% of the patients. The
      standard risk factors associated with cardiovascular mortality were found in the
      patients who died of these causes, that is, age, sex, smoking, diabetes, total
      cholesterol, and previous vascular status. After adjustment for risk factors,
      myocardial infarction was significantly associated with age, sex and total
      cholesterol in patients who received primary prevention care. CONCLUSION: This
      study showed the feasibility of tracing a cohort of dyslipidemic patients with
      cardiovascular risk factors seen in an endocrinology department. It enabled a
      pragmatic assessment of a specific at-risk French population and a description of
      the compliant and noncompliant patients.

PMID- 18065191
TI  - The influence of culture conditions on vasculitis and anaphylactoid shock induced
      by fungal pathogen Candida albicans cell wall extract in mice.
AB  - To explore whether Candida cell wall mannan is responsible for induction of
      vasculitis similar to Kawasaki syndrome and anaphylactoid shock in mice, we
      examined the biological effects of various mannan structures from Candida cell
      wall extracts prepared using various culture conditions. Intraperitoneal
      injection of 3 of 4 Candida cell wall extracts dramatically induced coronary
      arteritis and acute anaphylactoid shock in mice; only the cell wall extract
      derived from YPD medium culture at 27 degrees C had no toxic effect. It is of
      note that these biological effects depended on culture conditions around the
      cells such as culture temperature and media. These conditions lead to the
      structural rearrangement of cell wall mannan as confirmed by reactivity against
      antisera and NMR spectroscopy. Since the expression of beta-1,2-linked mannan
      varies dramatically between biologically active and inactive mannan, beta-1,2
      linked mannan might negatively affect Candida cell wall extract-induced coronary
      arteritis and acute anaphylactoid shock in mice. Our findings indicate that
      Candida cell wall mannan might contribute to coronary arteritis and acute shock,
      and that an alteration of mannan structure could be responsible for Candida
      pathogenicity.

PMID- 18065193
TI  - Ethylmercury and breastfeeding as confounders in outcomes of functional
      programming: Where are they?

PMID- 18065194
TI  - Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium.
AB  - Cadmium (Cd) is a potential pollutant of the environment. It manifests cyto-toxic
      effects in different organs in animals. In the present study, intraperitoneal
      injection of CdCl(2) (1mg/kg body weight) increased lipid peroxidation in Swiss
      mice testes indicating oxidative stress during 5th to 8th week of post-treatment
      . The enzymatic activity of superoxide dismutase (SOD), catalase (CT) and
      peroxidase (PD) were significantly decreased over the post-treatment phase in Cd
      treated mice testes compared to vehicle controls. Further, ascorbic acid content
      also declined significantly in Cd-exposed mice testes. Following Cd treatment, a
      marked increase in sperm abnormality percentage and significant decrease in sperm
      count was observed. The purpose of the present study was to evaluate the effect
      of vitamins C and E supplementation on Cd-treated mice testes. Therefore, Cd
      treated mice groups were injected with vitamins C and E, separately, to assess
      the effect of the vitamins in combating Cd-induced cytotoxicity and other
      manifestations. Supplementation of vitamin C (10mg/kg body weight) and vitamin E
      (100mg/kg body weight) to Cd-induced mice groups declined lipid peroxidation,
      increased sperm count profile, depressed the percentage of sperm abnormality,
      increased the activity of antioxidant enzymes mentioned above and also increased
      the concentration of ascorbic acid to a measurable extent. The role of vitamins
      in reducing oxidative stress-related effects on spermatogenesis in Cd-treated
      Swiss mice testes have been reported.

PMID- 18065195
TI  - Quantification of benzo[a]pyrene and other PAHs in the serum and follicular fluid
      of smokers versus non-smokers.
AB  - Cigarette smoking is a well-established reproductive hazard that has been linked
      with decreased fertility in both smokers and those exposed to second hand smoke.
      The chemical components responsible for the reproductive toxic effects of
      cigarette smoke are unknown. Moreover, exposure of reproductive tissues to the
      chemical constituents of cigarette smoke is largely unknown. Therefore, we
      measured the levels of benzo[a]pyrene (B[a]P), and other polycyclic aromatic
      hydrocarbons (PAH) present in cigarette smoke, in the serum and follicular fluid
      of women exposed to mainstream (n=19) and side stream smoke (n=7) compared to non
      smokers (n=10). Women exposed to mainstream smoke had significantly higher levels
      of B[a]P (1.32+/-0.68ng/ml) in their follicular fluid compared to side stream
      exposed (0.05+/-0.01ng/ml) or their non-smoking (0.03+/-0.01ng/ml) counterparts.
      More importantly we found significantly higher (p<0.001) levels of B[a]P in the
      follicular fluid of women who did not conceive (1.79+/-0.03ng/ml) compared to
      those that achieved a pregnancy (0.08+/-0.03ng/ml). Other PAHs known to be
      present in cigarette smoke were also detectable in both serum and follicular
      fluid of study subjects studied but with lower frequency compared to B[a]P and no
      differences in serum or follicular fluid levels between the groups could be
      demonstrated. The important finding that B[a]P reaches the follicular fluid and
      the fact that it is found at much higher levels in women who smoke provides
      further evidence that of the many toxicants present in cigarette smoke, B[a]P may
      be a key compound that is central to the documented adverse effects of cigarette
      smoke on follicular development and subsequent fertility.

PMID- 18065196
TI  - The methoxychlor metabolite, HPTE, directly inhibits the catalytic activity of
      cholesterol side-chain cleavage (P450scc) in cultured rat ovarian cells.
AB  - Exposure to the pesticide methoxychlor in rodents is linked to impaired steroid
      production, ovarian atrophy and reduced fertility. Following in vivo
      administration, it is rapidly converted by the liver to 2,2-bis-(p-hydroxyphenyl)
      1,1,1-trichloroethane (HPTE), the reported active metabolite. Both methoxychlor
      and HPTE have weak estrogenic and antiandrogenic activities, and these effects
      are thought to be mediated through the estrogen and androgen receptors,
      respectively. Previous in vivo studies on methoxychlor exposure to female animals
      have demonstrated decreased progesterone production but no change in serum
      estrogen levels. We recently showed that HPTE specifically inhibits the P450
      cholesterol side-chain cleavage (P450scc, CYP11A1) step resulting in decreased
      androgen production by cultured rat testicular Leydig cells. The current studies
      examined the mechanism of action of HPTE on progesterone production by cultured
      ovarian cells (granulosa and theca-interstitial) from pregnant mare serum
      gonadotropin-primed immature rats. In addition, we evaluated whether the effects
      of HPTE on rat ovarian cell progesterone biosynthesis were mediated through the
      estrogen or androgen receptors. Exposure to HPTE (0, 10, 50 or 100nM) alone
      progressively inhibited progesterone formation in cultured theca-interstitial and
      granulosa cells and the P450scc catalytic activity in theca-interstitial cells in
      a dose-dependent manner with significant declines starting at 50nM. However, HPTE
      did not change mRNA levels of the P450scc system (P450scc, adrenodoxin reductase
      and adrenodoxin) as well as P450scc protein levels. Of interest, estradiol,
      xenoestrogens (bisphenol-A or 4-tert-octylphenol), a pure antiestrogen (ICI
      182,780), or antiandrogens (4-hydroxyflutamide or the vinclozolin metabolite M
      2), had no effect on progesterone production even at 1000nM. Co-treatment of HPTE
      with ICI 182,780 did not block the effect of HPTE on progesterone formation.
      These studies suggest that the decline in progesterone formation following
      exposure to HPTE in cultured ovarian cells is associated with the inhibition of
      catalytic activity of P450scc at least in theca-interstitial cells. This action
      does not appear to be mediated through the estrogen or androgen receptor
      signaling pathways, and other chemicals exhibiting estrogenic, antiestrogenic or
      antiandrogenic properties do not mimic its effect on ovarian steroid production.

PMID- 18065197
TI  - Melanin-concentrating hormone projections to areas involved in somatomotor
      responses.
AB  - The lateral hypothalamic area (LHA) participates in the integration of sensory
      information and somatomotor responses associated with hunger and thirst. Although
      the LHA is neurochemically heterogeneous, a particularly high number of cells
      express melanin-concentrating hormone (MCH), which has been reported to play a
      role in energy homeostasis. Treatment with MCH increases food intake, and MCH
      mRNA is overexpressed in leptin-deficient (ob/ob) mice. Mice lacking both MCH and
      leptin present reduced body fat, mainly due to increased resting energy
      expenditure and locomotor activity. Dense MCH innervation of the cerebral motor
      cortex (MCx) and the pedunculopontine tegmental nucleus (PPT), both related to
      motor function, has been reported. Therefore, we postulated that a specific group
      of MCH neurons project to these areas. To investigate our hypothesis, we injected
      retrograde tracers into the MCx and the PPT of rats, combined with
      immunohistochemistry. We found that 25% of the LHA neurons projecting to the PPT
      were immunoreactive for MCH, and that 75% of the LHA neurons projecting to the
      MCx also contained MCH. Few MCH neurons were found to send collaterals to both
      areas. We also found that 15% of the incerto-hypothalamic neurons projecting to
      the PPT expressed MCH immunoreactivity. Those neurons preferentially innervated
      the rostral PPT. In addition, we observed that the MCH neurons express glutamic
      acid decarboxylase mRNA, a gamma-aminobutyric acid (GABA) synthesizing enzyme. We
      postulate that MCH/GABA neurons are involved in the inhibitory modulation of the
      innervated areas, decreasing motor activity in states of negative energy balance.

PMID- 18065198
TI  - Characterization of cochlear nucleus principal cells of Meriones unguiculatus and
      Monodelphis domestica by use of calcium-binding protein immunolabeling.
AB  - Antibodies directed against calcium-binding proteins (CaBPs) parvalbumin,
      calbindin-D28k and calretinin were used as neuronal markers to identify and
      characterize different principal cell types in the mammalian cochlear nucleus.
      For this purpose, double immunofluorescence labeling and the combination of CaBP
      labeling with pan-neuronal markers were applied to analyze the CaBPs distribution
      in neurons of the cochlear nucleus (CN) of the Mongolian gerbil (Meriones
      unguiculatus) and the gray short-tailed opossum (Monodelphis domestica). Despite
      of the fact, that these two mammalian species are not closely related, principal
      cell types in the CN of the two species showed many corresponding morphological
      features and similarities in immunolabeling of the CaBPs. Parvalbumin seems not
      to be suited as a differential neuronal marker in the CN since it is expressed by
      almost all neurons. In contrast, calbindin and calretinin were more restricted to
      specific cell types and showed a mostly complementary labeling pattern. As one of
      the most interesting findings, calbindin and calretinin were predominantly found
      in subpopulations of globular bushy cells and octopus cells in the ventral CN.
      Such a neuron-specific CaBP-expression in subpopulations of morphologically
      defined cell types argues for a more refined classification of CN cell types in
      Meriones and Monodelphis. Additionally, other cell types (cartwheel cells,
      unipolar brush cells, fusiform cells) were marked with calbindin or calretinin as
      well. Calretinin staining was predominantly observed in auditory nerve fibers and
      their endings including endbulbs of Held in Meriones. Spherical bushy cells
      showed a different calretinin-immunolabeling in Meriones and Monodelphis. This
      species-specific difference may be related to adaptive differences in auditory
      function.

PMID- 18065199
TI  - Functional training for initiating joint attention in children with autism.
AB  - The present study aimed to examine the controlling variables for initiating joint
      attention (IJA) in three children with autism. During the baseline, target
      objects were presented in a location where the child could see them, but the
      adult could not, and the emergence of IJA was assessed. Children with autism
      showed some IJA skills during the baseline, but none initiated pointing. In
      training, the motivating operation for IJA was manipulated by using each child's
      preferred materials as targets of joint attention. It was found that more
      frequent and functional joint attention behaviors were emitted following
      training. The present study suggests that difficulties in IJA in children with
      autism could be partly explained by restricted interests in children with autism.

PMID- 18065200
TI  - The MHC type 1 diabetes susceptibility gene is centromeric to HLA-DQB1.
AB  - HLA-DQB1 is widely considered to be the major histocompatibility complex (MHC)
      susceptibility gene for type 1 diabetes (T1D). However, since inheritance of the
      gene in T1D is recessive, the presence of the protective HLA-DQB1 0602 allele
      with normal nucleotide sequence in some patients raises the question of whether
      HLA-DQB1 is not the susceptibility locus itself but merely a good marker. HLA
      DQB1 0602 is part of a conserved extended haplotype (CEH) [HLA-B7, SC31, DR2]
      (B7, DR2) with fixed DNA over more than 1Mb of genomic DNA that normally carries
      a protective allele at the true susceptibility locus. We postulated that, in
      patients with HLA-DQB1 0602, the protective allele at the susceptibility locus
      has been replaced by a susceptibility allele through an ancient crossover at
      meiosis centromeric to HLA-DQB1. We analyzed single nucleotide polymorphisms
      (SNPs) distinguishing the HLA-DQA2 (the first expressed gene centromeric to HLA
      DQB1) allele on the normal HLA-B7, DR2 CEH from those on susceptibility CEHs in
      T1D patients and controls with HLA-DQB1 0602. All but 1 of 20 healthy control HLA
      DQB1 0602 haplotypes had identical (consensus) first intron HLA-DQA2 5-SNP
      haplotypes. Fifteen of 19 patients with HLA-DQB1 0602 were homozygous for 1 or
      more HLA-DQA2 SNPs differing from consensus HLA-DQA2 SNPs, providing evidence of
      crossover involving the HLA-DQA2 locus. The remaining 4 patients were
      heterozygous at all positions and therefore uninformative. The loss of dominant
      protection usually associated with HLA-DQB1 0602 haplotypes is consistent with a
      locus centromeric to HLA-DQB1 being a major determinant of MHC-associated
      susceptibility, and perhaps the true T1D susceptibility locus.

PMID- 18065201
TI  - IL-1beta-stimulated activation of ERK1/2 and p38alpha MAPK mediates the
      transcriptional up-regulation of IL-6, IL-8 and GRO-alpha in HeLa cells.
AB  - Epithelial cells represent the first line of defense against infection. Here we
      have studied the production of inflammatory mediators induced by IL-1beta in the
      HeLa epithelial cell line. We found that GRO-alpha, IL-6 and IL-8 were the only
      three inflammatory mediators elevated out of 36 tested. Specific inhibition of
      p38alpha MAP kinase or preventing the activation of ERK1/ERK2 partially reduced
      the production of these substances, while the combined blockade of both pathways
      almost abolished secretion. The suppression of these signaling pathways mainly
      reduced transcription of the genes encoding GRO-alpha, IL-6 and IL-8, rather than
      affecting mRNA stability, translation or secretion. The production of these three
      inflammatory mediators was shown to account for the ability of the HeLa cell
      culture medium to stimulate the migration of monocytes/macrophages, suggesting a
      key role for p38 MAPK and ERK1/ERK2 in orchestrating the epithelial cell response
      to infection.

PMID- 18065202
TI  - Effects of isoflavones on the coagulation and fibrinolytic system of
      postmenopausal women.
AB  - OBJECTIVE: We evaluated the effects of soy isoflavone supplementation on
      hemostasis in healthy postmenopausal women. METHODS: In this double-blinded,
      placebo-controlled study, 47 postmenopausal women 47-66 y of age received 40 mg
      of soy isoflavone (n = 25) or 40 mg of casein placebo (n = 22) once a day for 6
      mo. Levels of factors VII and X, fibrinogen, thrombin-antithrombin complex,
      prothrombin fragments 1 plus 2, antithrombin, protein C, total and free protein
      S, plasminogen, plasminogen activator inhibitor-1, and D-dimers were measured at
      baseline and 6 mo. Urinary isoflavone concentrations (genistein and daidzein)
      were measured as a marker of compliance and absorption using high-performance
      liquid chromatography. Baseline characteristics were compared by unpaired
      Student's t test. Within-group changes and comparison between the isoflavone and
      casein placebo groups were determined by a mixed effects model. RESULTS: The
      levels of hemostatic variables did not change significantly throughout the study
      in the isoflavone group; however, the isoflavone group showed a statistically
      significant reduction in plasma concentration of prothrombin fragments 1 plus 2;
      both groups showed a statistically significant reduction in antithrombin, protein
      C, and free protein S levels. A significant increase in D-dimers was observed
      only in the isoflavone group. Plasminogen activator inhibitor-1 levels increased
      significantly in the placebo group. However, these changes were not statistically
      different between groups. CONCLUSION: The results of the present study do not
      support a biologically significant estrogenic effect of soy isoflavone on
      coagulation and fibrinolysis in postmenopausal women. However, further research
      will be necessary to definitively assess the safety and efficacy of isoflavone.

PMID- 18065203
TI  - Smoking status relationships with the food and fluid intakes of free-living
      humans.
AB  - OBJECTIVE: The relation of cigarette smoking to food and fluid intakes was
      studied. METHODS: Ninety-nine smoking and 551 non-smoking free-living adult
      humans provided a detailed record of their eating and drinking in 7-d diaries.
      RESULTS: Cigarette smoking was associated with significant changes in overall
      intakes and meal pattern. Smokers had higher intakes of fluids in the form of
      drinks due to higher levels of alcohol and coffee/tea consumption. Smokers were
      less hungry but more responsive to social facilitation and time of day. There
      were also substantial gender differences in smoking relations to intake, with
      male smokers tending to have higher overall and meal intakes particularly of fats
      than non-smokers, whereas female smokers tended to have lower overall intakes,
      fewer meals, and lower amounts of carbohydrates than non-smokers. Male smokers
      tended to be less responsive to their before-meal stomach content, their level of
      hunger, and the palatability of the meal than non-smokers, whereas females tend
      to be more responsive to all of these influences on meal size. CONCLUSION: These
      results suggest that smoking has very few direct simple effects on intake but
      rather influences intake indirectly through its covariation with alcohol and
      caffeine intakes and with dietary restraint and that smoking has different,
      sometimes opposite, influences in males and females.

PMID- 18065204
TI  - Depletion of plasma antioxidants in surgical intensive care unit patients
      requiring parenteral feeding: effects of parenteral nutrition with or without
      alanyl-glutamine dipeptide supplementation.
AB  - OBJECTIVES: Antioxidant depletion is common in critically ill patients. This
      study was designed to determine the effects of parenteral nutrition (PN), with or
      without glutamine (Gln) supplementation, on systemic antioxidant status in adult
      patients after major surgery who required PN in the surgical intensive care unit
      (SICU) setting. METHODS: Fifty-nine patients in the SICU who required PN after
      pancreatic surgery or cardiac, vascular, or colonic (non-pancreatic) surgery were
      randomized in a double-blinded study to receive standard PN (Gln-free) or Gln
      supplemented PN (Gln-PN) in which Gln was provided as alanyl-Gln dipeptide.
      Conventional PN vitamin and mineral doses were administered to all subjects.
      Plasma concentrations of the antioxidant glutathione (GSH) and the antioxidant
      nutrients alpha-tocopherol, vitamin C, and zinc were determined at baseline
      (initiation of study PN) and again after 7 d of study PN. Data were analyzed for
      the total study cohort and within the pancreatic surgery and non-pancreatic
      (cardiac, vascular, and colonic) surgery patient subgroups. RESULTS: Mean plasma
      antioxidant concentrations were within or slightly below the normal ranges at
      baseline. However, a larger percentage of patients demonstrated below-normal
      baseline plasma concentrations of GSH (59%), vitamin C (59%), and zinc (68%),
      respectively. A smaller percentage of patients exhibited below-normal plasma
      alpha-tocopherol levels (21%). Study PN significantly improved plasma zinc levels
      in the entire study group and in each surgical subgroup. Gln-PN significantly
      improved the change in plasma levels of reduced GSH from baseline to day 7 in the
      non-pancreatic surgery patients (PN -0.27 microM versus Gln-PN +0.26 microM, P <
      0.03). CONCLUSION: Low plasma levels of key antioxidants were common in this
      group of patients in the SICU despite administration of PN containing
      conventional micronutrients. Compared with standard PN, Gln-supplemented PN
      improved plasma GSH levels in patients in the SICU after cardiac, vascular, or
      colonic operations.

PMID- 18065205
TI  - Mandatory fortification with folic acid in the United States is associated with
      increased expression of DNA methyltransferase-1 in the cervix.
AB  - OBJECTIVE: The objective of this study was to evaluate whether mandatory
      fortification of grain products with folic acid in the United States is
      associated with changes in DNA methyltransferase-1 (Dnmt-1) expression in cells
      involved in cervical carcinogenesis. METHODS: Archived specimens of cervical
      intraepithelial neoplasia (CIN) diagnosed before (1990-1992) and after (2000
      2002) mandatory folic acid fortification were used to examine the expression of
      Dnmt-1 in specific lesions involved in cervical carcinogenesis by
      immunohistochemistry. The total number of lesions examined was 101 in the
      prefortification period and 96 in the postfortification period.
      Immunohistochemical staining for Dnmt-1, its assessment, and data entry were
      blinded with regard to the fortification status. RESULTS: Age- and race-adjusted
      mean percentage of cells positive for Dnmt-1 or the Dnmt-1 score was
      significantly higher in all lesion types (i.e., normal cervical epithelium,
      reactive cervical epithelium, metaplastic cervical epithelium, CIN, or carcinoma
      in situ) detected in the postfortification period compared with the
      prefortification period (P < 0.05, all comparisons). The degree of Dnmt-1 was
      significantly higher (P < 0.0001) in CIN > or = 2 lesions compared with CIN < or
      = 1 lesions, regardless of the fortification group. CONCLUSION: These results
      suggest that mandatory fortification with folic acid in the United States seems
      to have resulted in a change in the degree of expression of Dnmt-1 in cells
      involved in cervical carcinogenesis. Because the approach we have taken to
      demonstrate these differences have limitations inherent to a study of this nature
      and this is the first study to report a folate fortification associated change in
      Dnmt-1, validating these results in other study populations and/or with other
      techniques of assessing Dnmt-1 will increase the scientific credibility of these
      findings.

PMID- 18065206
TI  - Genetic examination of the PLXNA2 gene in Japanese and Chinese people with
      schizophrenia.
AB  - Aberrant neuronal development is one of the integrative theories for the etiology
      of schizophrenia. The plexin A2 (PLXNA2) gene is one of the receptor genes for
      axonal guidance factors. Recently, four single nucleotide polymorphisms (SNPs),
      rs841865, rs752016, rs1327175 and rs2498028, from the PLXNA2 genomic interval
      have been reported to be associated with schizophrenia in samples from European
      Americans, Latin Americans and Asian Americans. We tested these four SNPs for
      association with disease in two Asian populations: 1140 case-control Japanese
      samples and 293 Chinese pedigrees (1163 samples). In the Japanese samples,
      significant differences in the allelic frequency and genotypic distribution of
      rs841865 (p=0.019 and 0.020, respectively) were observed between cases and
      controls. Haplotype analysis also revealed a significant association of the gene
      with the disease (global p=0.028). In contrast, there was no genetic contribution
      of PLXNA2 to Chinese schizophrenia, either by linkage analysis or association
      tests (allelic and haplotypic transmission disequilibrium tests). These findings
      suggest that PLXNA2 confers a varying genetic risk for schizophrenia among
      different populations.

PMID- 18065207
TI  - The role of pro-inflammatory factors in mediating the effects on the fetus of
      prenatal undernutrition: implications for schizophrenia.
AB  - Exposure to prenatal undernutrition or malnutrition increases the risk of
      schizophrenia, although little is known about the mechanism. Pro-inflammatory
      factors are critical in brain development, and are believed to play an important
      role in neurodevelopmental disorders associated with prenatal exposure to
      infection, including schizophrenia. However it is not known whether pro
      inflammatory factors also mediate the effects on the fetus of prenatal
      malnutrition or undernutrition. In this study, we established a new prenatal
      undernourished rat model induced by maternal exposure to a diet restricted to 50%
      of the low (6%) protein diet (RLP50). We observed the disappearance of maternal
      nest-building behavior in the RLP50 dams, increased levels of TNFA and IL6 in the
      placentas (P<0.001; P=0.879, respectively) and fetal livers (P<0.001; P<0.05,
      respectively), and a decrease in the fetal brains (P<0.05; P<0.01, respectively).
      Our results are similar to previous studies of maternal infection, which implies
      that a common pathway mediated by pro-inflammatory factors may contribute to the
      brain development, consequently increasing the risk of schizophrenia and other
      psychiatric diseases programmed by varied maternal adversities. We also provide a
      new prenatal undernourished model for researching prenatal problems, which
      differs from previous malnourished model in terms of the maternal behavior of
      dams and of observed pro-inflammatory factor levels in fetal tissues.

PMID- 18065208
TI  - Acute bacterial prostatitis in Korea: clinical outcome, including symptoms,
      management, microbiology and course of disease.
AB  - The Korean Association of Urogenital Tract Infection and Inflammation (KAUTII)
      conducted a multicentre, retrospective analysis of acute bacterial prostatitis
      (ABP) to document clinical features, management, microbiology and the course of
      disease. The clinical records of 473 cases compatible with a confirmed diagnosis
      of ABP from 16 urological centres between 2001 and 2005 were reviewed.
      Susceptibility of the organisms causing ABP, including Escherichia coli, to
      ciprofloxacin was shown to be very low, fuelling debate as to the efficacy of
      ciprofloxacin against uropathogens in Korea. When subcategorised according to
      history of prior manipulation of the lower urinary tract, there were distinct
      differences between ABP patients with or without a history of prior manipulation
      with regard to overall clinical and microbiological features. The difference in
      the distribution of pathogens between the two groups as well as the difference in
      susceptibility between E. coli and other pathogens should influence empirical
      antibiotic treatment. In the group with a history of prior manipulation of the
      lower urinary tract, ciprofloxacin or cephalosporins alone are an inadequate
      choice and the combination of cephalosporins and amikacin is recommended for
      empirical therapy.

PMID- 18065210
TI  - Analysis of cis-regulatory elements controlling spatio-temporal expression of T
      brain gene in sea urchin, Hemicentrotus pulcherrimus.
AB  - In sea urchin development, micromere descendants play important roles in
      skeletogenesis and induction of gastrulation. We previously reported that the T
      brain homolog of sea urchin Hemicentrotus pulcherrimus, HpTb expresses
      specifically in micromere descendants and is required for induction of
      gastrulation and skeletogenesis. Thus, HpTb is thought to play important roles in
      the function of micromere-lineage cells. To identify cis-regulatory regions
      responsible for spatio-temporal gene expression of HpTb, we isolated
      approximately 7kb genomic region of HpTb gene and showed that GFP expression
      driven by this region exhibits the spatio-temporal pattern corresponding
      substantially to that of endogenous HpTb expression. Deletion of
      interspecifically conserved C2 and C4 regions resulted in an increase of ectopic
      expression. Mutations in Hairy family and Snail family consensus sequences in C1
      and C2 regions also increased ectopic expression. Furthermore, we demonstrated
      that C4 region functions as enhancer, and that three Ets family consensus
      sequences are involved in this activity but not in spatial regulation. Therefore,
      we concluded that expression of HpTb gene is regulated by multiple cis-regulatory
      elements.

PMID- 18065211
TI  - Comparative effects of different triazole compounds on antioxidant metabolism of
      Solenostemon rotundifolius.
AB  - The effect of different triazole compounds, viz., triadimefon (TDM) and
      hexaconazole (HEX) treatments on the antioxidant metabolism of Solenostemon
      rotundifolius Poir., Morton plants was investigated in the present study under
      pot culture. Plants were treated with TDM at 15 mg l(-1) and HEX at 10 mg l(-1)
      separately by soil drenching on 80, 110 and 140 days after planting (DAP). The
      plants were harvested randomly on 90, 120 and 150 DAP for determining the effect
      of both the triazoles on non-enzymatic antioxidant contents like ascorbic acid
      (AA), reduced glutathione (GSH) and alpha-tocopherol (alpha-toc), activities of
      antioxidant enzymes like superoxide dismutase (SOD) and ascorbate peroxidase
      (APX). All the analyses were made in leaf, stem and tubers of both control and
      treated plants. It was found that both these triazole compounds have profound
      effects on the antioxidant metabolism and caused an enhancement in both non
      enzymatic and enzymatic antioxidant potentials under treatments. These results
      suggest that, the application of triazoles may be a useful tool to increase the
      antioxidant production in S. rotundifolius and thereby make it an economical food
      crop.

PMID- 18065209
TI  - Frizzled-Dishevelled signaling specificity outcome can be modulated by Diego in
      Drosophila.
AB  - Members of the Frizzled (Fz) family of seven-pass transmembrane receptors are
      required for the transduction of both Wnt-Fz/beta-catenin and Fz/planar cell
      polarity (PCP) signals. Although both pathways transduce signals via interactions
      between Fz and the cytoplasmic protein Dishevelled (Dsh), each pathway has
      specific and distinct effectors. One explanation for the pathway specificity is
      that signal-induced conformational changes result in unique Fz-Dsh interactions.
      Our mutational analyses of Fz-Dsh activities in vivo do however not support this
      model, since both pathways are affected by all mutations tested. Alternatively,
      the interaction of Fz or Dsh with other proteins could modulate the signaling
      outcome. We examined the role of a Dsh-binding PCP molecule, Diego (Dgo), in both
      Wnt-Fz/beta-catenin and Fz/PCP signaling. Both loss-of-function and gain-of
      function results suggest that Dgo promotes Fz-Dsh/PCP signaling at the expense of
      Wnt-Fz/beta-catenin signaling. Our data suggest that Dgo sequesters Dsh to a
      functionally distinct Fz/PCP signaling compartment within the cell.

PMID- 18065212
TI  - Pulmonary surfactant adsorption is increased by hyaluronan or polyethylene
      glycol.
AB  - In acute lung injuries, inactivating agents may interfere with transfer
      (adsorption) of pulmonary surfactants to the interface between air and the
      aqueous layer that coats the interior of alveoli. Some ionic and nonionic
      polymers reduce surfactant inactivation in vitro and in vivo. In this study, we
      tested directly whether an ionic polymer, hyaluronan, or a nonionic polymer,
      polyethylene glycol, enhanced adsorption of a surfactant used clinically. We used
      three different methods of measuring adsorption in vitro: a modified pulsating
      bubble surfactometer; a King/Clements device; and a spreading trough. In addition
      we measured the effects of both polymers on surfactant turbidity, using this
      assay as a nonspecific index of aggregation. We found that both hyaluronan and
      polyethylene glycol significantly increased the rate and degree of surfactant
      material adsorbed to the surface in all three assays. Hyaluronan was effective in
      lower concentrations (20-fold) than polyethylene glycol and, unlike polyethylene
      glycol, hyaluronan did not increase apparent aggregation of surfactant.
      Surfactant adsorption in the presence of serum was also enhanced by both polymers
      regardless of whether hyaluronan or polyethylene glycol was included with serum
      in the subphase or added to the surfactant applied to the surface. Therefore,
      endogenous polymers in the alveolar subphase, or exogenous polymers added to
      surfactant used as therapy, may both be important for reducing inactivation of
      surfactant that occurs with various lung injuries.

PMID- 18065214
TI  - CHART revisited: a conservative approach for advanced head and neck cancer.
AB  - AIMS: To evaluate the long-term late adverse effects and treatment outcome in
      patients treated for advanced squamous cell carcinomas of the head and neck with
      continuous, hyperfractionated, accelerated radiation therapy (CHART). MATERIALS
      AND METHODS: One hundred and twenty-six consecutive patients were entered into a
      non-randomised study of CHART alone with salvage treatment reserved for
      locoregional recurrence. The primary end points were locoregional control and
      late treatment-related morbidity. Time-incidence curves and statistical
      comparisons were obtained by computing actuarial event-free intervals using the
      product-limit (Kaplan-Meier) method. The prevalence rate of adverse effects was
      calculated using yearly intervals. Patients have been followed over a 15-year
      period. RESULTS: The actuarial 12-year locoregional recurrence-free rate after
      radiotherapy alone was 46%, which was increased by 15% with the use of salvage
      treatment (hazard ratio for recurrence with CHART alone 1.23, confidence interval
      1.017-1.494; P=0.033). Actuarial estimates of severe adverse effects at this time
      were: dysphagia 12% (grade 4); subcutaneous fibrosis 3%; xerostomia 15%. Ulcers
      of mucous membranes were observed in 18% of patients. As expected, the prevalence
      of events was lower than that calculated by the life-table method. CONCLUSIONS:
      Few, if any, studies have documented and reported on long-term adverse effects
      and treatment outcomes as in this pilot trial of CHART (median follow-up time of
      those alive at 5 years or more is 11 years and the maximum follow-up time is 18
      years). The low level of moderate to severe long-term morbidity together with a
      good and maintained level of locoregional tumour control indicates that CHART
      achieves a therapeutic benefit in patients with advanced squamous cell carcinoma
      of the head and neck.

PMID- 18065213
TI  - Cytotoxicity of contact lens multipurpose solutions: role of oxidative stress,
      mitochondrial activity and P2X7 cell death receptor activation.
AB  - OBJECTIVE: To investigate the cytotoxicity of multipurpose solutions used for
      contact lens disinfection. METHODS: Four multipurpose solutions (Optifree
      containing quaternary ammonium as preservative, Renu, Solocare and Complete
      containing polyhexamethylene biguanide as preservative) were incubated on a
      conjunctival cell line to evaluate their capacity to induce necrosis (neutral red
      test), intracellular redox status alteration (Alamar Blue test), reactive oxygen
      species overproduction (DCFH-DA and dihydroethidium tests), mitochondrial
      alterations (NonylAcridine Orange and JC-1 tests) and to activate P2X7 cell death
      receptor (YO-PRO-1 test). Tests were performed using cytofluorometry and inverted
      fluorescence microscopy. RESULTS: Our results showed that multipurpose solutions
      induced necrosis, in addition to oxidative stress. Optifree induced oxidative
      stress with increased mitochondrial mass, Renu, Solocare and Complete induced
      whether a decrease in reactive oxygen species production with mitochondrial
      alterations, or an increase in reactive oxygen species production, but each
      solution stimulated P2X7 cell death receptor activation. Early stimulation of
      P2X7 cell death receptor, prior to any superoxide production, demonstrated the
      possible involvement of this receptor in the oxidative stress process.
      CONCLUSION: These new findings suggest that most of multipurpose solutions are
      toxic with oxidative stress and apoptosis induction.

PMID- 18065215
TI  - Uterine carcinosarcoma in a patient with hereditary non-polyposis coli.

PMID- 18065216
TI  - Transdermal delivery of penetrants with differing lipophilicities using O
      acylmenthol derivatives as penetration enhancers.
AB  - To develop more effective compounds as penetration enhancers, O-acylmenthol
      derivatives were synthesized by l-menthol and saturated fatty acid, O
      ethylmenthol (MET), was also synthesized as a reference compound. Their promoting
      activity on the percutaneous absorption of five model drugs, 5-fluorouracil (5
      FU), isosorbide dinitrate (ISDN), lidocaine (LD), ketoprofen (KP), indomethacin
      (IM), which were selected based on their lipophilicity represented by log KO/W,
      was tested in vitro across full thickness rat skin with each of the evaluated
      drugs in saturated donor solution. Only 2-isopropyl-5-methylcyclohexyl
      tetradecanoate (C14 alkyl chain) had promoting effects on the percutaneous
      permeation of 5-FU; 2-isopropyl-5-methylcyclohexyl hexanoate (C6 alkyl chain),
      which increased the permeation coefficient (P) 1.91-fold, had the highest
      permeation for ISDN; in the case of LD, the highest increase in P was observed
      with 2-isopropyl-5-methylcyclohexyl heptanoate (C7 alkyl chain), which increased
      the P by 1.58-fold; MET, which increased the P by 2.02-fold, provided the best
      enhancement for KP; 2-isopropyl-5-methylcyclohexyl heptanoate (C7 alkyl chain)
      produced the highest increase in P, 3.70-fold for IM. These results suggest that
      some newly designed percutaneous absorption enhancers have the potential to
      enhance drugs with different lipophilicities. A chain length of C6-C10 seemed to
      be favorable for lipophilic drugs, while C14 was the most effective enhancer for
      hydrophilic drug (5-FU).

PMID- 18065218
TI  - Plastics - still young, but having a mature impact.

PMID- 18065217
TI  - How T cells get grip on lipid antigens.
AB  - Lipid antigens are presented to T cells as complexes formed with CD1 family
      members. The hydrophobic nature of lipids influences how they remain in
      biological fluids, are distributed within cells, and are handled to become
      immunogenic. Continuously expanding knowledge shows how lipids are internalized
      by APC, traffic through the endocytic system, are processed to generate
      immunogenic molecules, and are loaded on CD1 proteins. The molecular bases of how
      lipids interact with CD1 and TCR are being defined. A breakthrough in the field
      has been the discovery that exogenous and endogenous lipids stimulate T cells
      which mount adaptive and innate-like responses. Disclosure of molecular
      protagonists and mechanisms of both responses has great promise for development
      of novel lipid-based vaccines and immunotherapies.

PMID- 18065219
TI  - Reductive hydrothermal treatment of sewage sludge.
AB  - The United States and the European Union each generate around 6900 million dry
      tons of sewage sludge annually. This is disposed of by land application,
      landfilling, incineration and other approaches. Reductive hydrothermal (HT)
      treatment refers here to simple aqueous systems heated and pressurized above 300
      degrees C/100 bar under anoxic and/or reducing conditions. The purpose of this
      study was to examine the HT treatment of municipal sewage sludge and infectious
      fecal microbial cultures with respect to waste volume reduction, biological
      sterilization, and the generation of usable hydrocarbon product mixtures. These
      endpoints from HT treatment also were compared to those from pyrolysis. HT at 400
      degrees C/150 bar transformed sewage sludge solids into complex gas phase (4%)
      and liquid (6%) hydrocarbon mixtures (approximately 11% combined yield), along
      with similar amounts (5%) of solid residues. HT products in the aqueous phase
      (e.g., alcohols) were present but not analysed. Viable mixed fecal cultures
      (10(9) colony forming units/mL) were completely sterilized by HT treatment, and a
      hydrocarbon mixture also was generated from the cells, but it was markedly
      different from that resulting from HT of the sludge. The hydrocarbon assemblage
      generated from the sludge included n-hydrocarbons (C9-C20) and alkyl substituted
      benzenes, phenols, and related compound series of higher mass (e.g., indanes,
      naphthalenes). Light aromatic parent compounds were significantly less abundant
      than their substituted C1-C5 alkyl series and there was a paucity of N-, O- and S
      heterocycles and polycyclic systems with more than three fused rings. This was
      different from the products of pyrolysis which were dominated by a relatively
      simple mixture of linear and branched hydrocarbons and their oxidized homologues
      (e.g., aldehydes).

PMID- 18065221
TI  - Multiple response optimization analysis for pretreatments of Tequila's stillages
      for VFAs and hydrogen production.
AB  - The objective of this work was study the effect of three pretreatments
      (alkalinization, thermical treatment, and sonication) on Tequila's stillages
      hydrolysis process in acidogenesis stage, through the following response
      variables: soluble chemical oxygen demand (CODs), total sugar and volatile fatty
      acids profile and the hydrogen production at the time. The stillages were subject
      to these pretreatments (according to a 2(3) factorial design); afterward they
      were transferred to a batch reactor at 35 degrees C and inoculated with an
      anaerobic digestor sludge. Multiple response optimization (MRO) analysis was done
      to find the global optimum for the response variables described above. This
      optimum is able to maximize simultaneously all these variables. It was found
      adequate to be useful hydrolyzing the organic matter present in Tequila's
      stillages. Mathematical models were fitted to observe the estimated effects of
      pretreatments on each response variable, then the MRO was applied.

PMID- 18065222
TI  - Targeting RNA with cysteine-constrained peptides.
AB  - A combined approach for targeting RNA with novel, biologically active ligands has
      been developed using a cyclic peptide library and in silico modeling. This
      approach has successfully identified novel cyclic peptide constructs that can
      target bTAR RNA. Subsequently, RNA/peptide interactions were effectively modeled
      using the HADDOCK docking program.

PMID- 18065223
TI  - The need for advanced breast cancer treatment guidelines: results of an internet
      based survey.
AB  - Although not curable, advanced breast cancer is treatable, however, treatment
      options are many and varied, and unlike early breast cancer (EBC), consistent
      guidelines are lacking. Breast cancer physicians were surveyed to assess the
      emotional impact of recurrence, factors affecting their treatment decisions, the
      role of guidelines in the management of advanced breast cancer and the need for
      new guidelines. Overall, distress levels were higher at recurrence than at first
      diagnosis of early breast cancer for both patients and physicians and the goal of
      treatment for this disease stage was to improve the patient's quality of life,
      delay disease progression and improve overall survival. While most respondents
      (96%) use the currently available guidelines, improvements are required,
      including the development of uniform global guidelines and recommendations for
      specific patient groups. Interactive computer programs and e-mail updates should
      also be utilised to ensure physicians are able to make fully informed decisions
      regarding optimum treatment.

PMID- 18065224
TI  - Aurora B kinase-dependent recruitment of hZW10 and hROD to tensionless
      kinetochores.
AB  - The mitotic checkpoint ensures proper chromosome segregation by monitoring two
      critical events during mitosis. One is kinetochore attachment to the mitotic
      spindle, and the second is the alignment of chromosomes at the metaphase plate,
      resulting in tension across sister kinetochores (reviewed in [1, 2]). Mitotic
      checkpoint proteins are known to accumulate at unaligned chromosomes that have
      not achieved proper kinetochore-microtubule attachments or established an
      adequate level of tension across sister kinetochores. Here, we report that hZW10
      and hROD, two components of the evolutionarily conserved RZZ complex, accumulate
      at kinetochores in response to the loss of tension. By using live-cell imaging
      and FRAP, we showed that the accumulation of hZW10 at tensionless kinetochores
      stems from a 4-fold reduction of kinetochore turnover rate. We also found that
      cells lacking hZW10 escape loss-of-tension-induced mitotic-checkpoint arrest more
      rapidly than those arrested in response to the lack of kinetochore-microtubule
      attachments. Furthermore, we show that pharmacological inhibition of Aurora B
      kinase activity with ZM447439 in the absence of tension, but not in the absence
      of kinetochore-microtubule attachments, results in the loss of hZW10, hROD, and
      hBub1 from kinetochores. We therefore conclude that Aurora B kinase activity is
      required for the accumulation of tension-sensitive mitotic-checkpoint components,
      such as hZW10 and hROD, in order to maintain mitotic-checkpoint arrest.

PMID- 18065225
TI  - Neurosurgery and the first fleet.
AB  - Several neurosurgical events occurred during the voyage of the First Fleet from
      England to Australia in 1787-1788. The early records also describe a number of
      head injuries during the first years of European settlement in Australia.

PMID- 18065226
TI  - Improved syntheses and applicability of different DOTA building blocks for
      multiply derivatized scaffolds.
AB  - DOTA (1,4,7,10-tetraazacyclodocecane-N,N',N'',N'''-tetraacetic acid), which forms
      extremely stable complexes with a large number of metal ions, is one of the most
      important and most commonly used chelators for in vivo applications such as
      cancer diagnosis and therapy. However, many of the published synthesis protocols
      for DOTA derivatives are complicated and give the products in low yields. Here we
      report improved synthesis routes for tris-tBu-DOTA, tris-benzyl-DOTA, and thiol
      DOTA, and also describe the synthesis of the novel compound tris-4-nitro-benzyl
      DOTA. In addition, we determined the applicability of the DOTA derivatives tris
      tBu-DOTA, thiol-DOTA, tris-benzyl-DOTA, tris-4-nitrobenzyl-DOTA, tris-allyl-DOTA,
      DOTA-PFP-ester, and DOTA-PNP-ester for multimerization reactions using amino
      functionalized PAMAM dendrimers of different sizes. Thiol-DOTA was found to be
      the best compound for efficient reactions with dendritic scaffolds generating
      highly homogeneous DOTA-multimers. This DOTA derivative could be quantitatively
      conjugated to a 128-mer dendrimer.

PMID- 18065227
TI  - Structure-activity relationships in the inhibition of monoamine oxidase B by 1
      methyl-3-phenylpyrroles.
AB  - 1-Methyl-3-phenyl-3-pyrrolines are structural analogues of the neurotoxin 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and like MPTP are selective
      substrates of monoamine oxidase B (MAO-B). As part of an ongoing investigation
      into the substrate properties of various 1-methyl-3-phenyl-3-pyrrolinyl
      derivatives, it is shown in the present study that their respective MAO-B
      catalyzed oxidation products act as reversible competitive inhibitors of the
      enzyme. The most potent inhibitor among the oxidation products considered was 1
      methyl-3-(4-trifluoromethylphenyl)pyrrole with an enzyme-inhibitor dissociation
      constant (K(i) value) of 1.30 microM. The least potent inhibitor was found to be
      1-methyl-3-phenylpyrrole with a K(i) value of 118 microM. The results of an SAR
      study established that the potency of MAO-B inhibition by the 1-methyl-3
      phenylpyrrolyl derivatives examined here is dependent on the Taft steric
      parameter (E(s)) and Swain-Lupton electronic constant (F) of the substituents
      attached to C-4 of the phenyl ring. Electron-withdrawing substituents with a
      large degree of steric bulkiness appear to enhance inhibition potency. Potency
      was also found to vary with the substituents at C-3, again with E(s) and F being
      the principal substituent descriptors.

PMID- 18065228
TI  - SAR studies of capsazepinoid bronchodilators. Part 2: Chlorination and catechol
      replacement in the A-ring.
AB  - Capsazepine as well as its derivatives and analogues are general inhibitors of
      constriction of human small airways. From a systematic variation of the
      capsazepine structure, divided into four regions, SARs were established. This
      paper concerns the chlorination of the A-ring as well as the replacement of the
      catechol with bioisosteric groups. It is revealed that chlorination of the A-ring
      has a profound effect on activity. Moreover, di-chlorination of the 6,7-dihydroxy
      1,2,3,4-tetrahydroisoquinoline structure results in a 10-fold increase in potency
      compared to capsazepine.

PMID- 18065229
TI  - A novel series of parenteral cephalosporins exhibiting potent activities against
      both Pseudomonas aeruginosa and other gram-negative pathogens. Part 2: Synthesis
      and structure-activity relationships.
AB  - A novel series of 7beta-[2-(2-amino-5-chloro-thiazol-4-yl)-2(Z)-((S)-1
      carboxyethoxyimino)acetamido]cephalosporins bearing various pyridinium groups at
      the C-3' position were synthesized and their in vitro antibacterial activities
      against gram-negative pathogens including Pseudomonas aeruginosa and several gram
      positive pathogens were evaluated. Among the cephalosporins prepared, we found
      that a cephalosporin bearing the 2-amino-1-(3-methylamino-propyl)-1H-imidazo[4,5
      b]pyridinium group at the C-3' position (8a) showed potent and well-balanced
      antibacterial activities against P. aeruginosa and other gram-negative pathogens
      including the strains which produce class C beta-lactamase and extended spectrum
      beta-lactamase (ESBL). Compound 8a also showed efficacious in vivo activity and
      high stability against AmpC beta-lactamase. These findings indicate that 2
      aminoimidazopyridinium having an aminoalkyl group at the 1-position as a C-3'
      side chain is suitable for cephalosporins bearing an aminochlorothiazolyl moiety
      and a carboxyethoxyimino moiety on the C-7 side chain.

PMID- 18065230
TI  - Synthesis and evaluation of antitumoral activity of ester and amide derivatives
      of 2-arylamino-6-trifluoromethyl-3-pyridinecarboxylic acids.
AB  - The synthesis and antitumoral activity of ester and amide derivatives of 2
      arylamino-6-trifluoromethyl-3-pyridinecarboxylic acids 8-58 is described.
      Trifluoromethylpyridine derivatives 8-58 were evaluated for their anticancer
      activity toward human tumoral cell lines by the National Cancer Institute (NCI).
      Most of them possess encouraging anticancer activity, having GI(50) values in the
      low micromolar to nanomolar concentration range. The 3,4,5-trimethoxyphenylamide
      44 was the most active, and it is now under review by NCI Biological Evaluation
      Committee for possible further studies.

PMID- 18065231
TI  - SAR studies of capsazepinoid bronchodilators. Part 1: The importance of the
      catechol moiety and aspects of the B-ring structure.
AB  - Capsazepine as well as its derivatives and analogues are general inhibitors of
      constriction of human small airways. From a systematic variation of the
      capsazepine structure, divided into four regions, SARs were established. This
      part concerns the catechol moiety of the A-ring as well as the 2,3,4,5-tetrahydro
      1H-2-azepine moiety (the B-ring) of capsazepine. It is revealed that a
      conformational constrain (as a fused ring) is important and that compounds with a
      six-membered B-ring (as a 1,2,3,4-tetrahydroisoquinoline) in general are more
      potent than the corresponding isoindoline, 2,3,4,5-tetrahydro-1H-2-benzazepine
      and 2,3,4,5-tetrahydro-1H-3-benzazepine derivatives.

PMID- 18065232
TI  - Rate enhancement of the oxidative folding of lysozyme by the use of aromatic
      thiol containing redox buffers.
AB  - Almost all therapeutic proteins and most extracellular proteins contain disulfide
      bonds. The production of these proteins in bacteria or in vitro is challenging
      due to the need to form the correctly matched disulfide bonds during folding. One
      important parameter for efficient in vitro folding is the composition of the
      redox buffer, a mixture of a small molecule thiol and small molecule disulfide.
      The effects of different redox buffers on protein folding, however, have received
      limited attention. The oxidative folding of denatured reduced lysozyme was
      followed in the presence of redox buffers containing varying concentrations of
      five different aromatic thiols or the traditional aliphatic thiol glutathione
      (GSH). Aromatic thiols eliminated the lag phase at low disulfide concentrations,
      increased the folding rate constant up to 11-fold, and improved the yield of
      active protein relative to GSH. The yield of active protein was similar for four
      of the five aromatic thiols and for glutathione at pH 7 as well as for
      glutathione at pH 8.2. At pH 6 the positively charged aromatic thiol provided a
      higher yield than the negatively charged thiols.

PMID- 18065233
TI  - Three-dimensional quantitative structure-activity relationship studies on novel
      series of benzotriazine based compounds acting as Src inhibitors using CoMFA and
      CoMSIA.
AB  - Comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA) were performed on a series of benzotriazine
      derivatives, as Src inhibitors. Ligand molecular superimposition on the template
      structure was performed by database alignment method. The statistically
      significant model was established of 72 molecules, which were validated by a test
      set of six compounds. The CoMFA model yielded a q(2)=0.526, non cross-validated
      R(2) of 0.781, F value of 88.132, bootstrapped R(2) of 0.831, standard error of
      prediction=0.587, and standard error of estimate=0.351 while the CoMSIA model
      yielded the best predictive model with a q(2)=0.647, non cross-validated R(2) of
      0.895, F value of 115.906, bootstrapped R(2) of 0.953, standard error of
      prediction=0.519, and standard error of estimate=0.178. The contour maps obtained
      from 3D-QSAR studies were appraised for activity trends for the molecules
      analyzed. Results indicate that small steric volumes in the hydrophobic region,
      electron-withdrawing groups next to the aryl linker region, and atoms close to
      the solvent accessible region increase the Src inhibitory activity of the
      compounds. In fact, adding substituents at positions 5, 6, and 8 of the
      benzotriazine nucleus were generated new compounds having a higher predicted
      activity. The data generated from the present study will further help to design
      novel, potent, and selective Src inhibitors as anticancer therapeutic agents.

PMID- 18065234
TI  - Pulmonary metastasectomy for colorectal cancer: weak evidence and no randomised
      trials.
AB  - The practice of pulmonary metastasectomy is widespread. A web-based survey run as
      part of the ESTS Working Group on pulmonary metastasectomy has provided some
      insights into similarities and variations in belief and practice [Internullo E,
      Cassivi S, Van Raemdonck D, Friedel G, Treasure T. Pulmonary metastasectomy: the
      state of the practice in Europe. Interact Cardiovasc Thorac Surg 2007;6(Suppl.
      2):S182. Ref Type: Abstract.]. What we do know from the work of the group and
      from a systematic review [Pfannschmidt J, Dienemann H, Hoffmann H. Surgical
      resection of pulmonary metastases from colorectal cancer: a systematic review of
      published series. Ann Thorac Surg 2007;84(July(1)):324-38.] is that there are no
      randomised outcome data to guide us. We rely on presumed benefit based on
      comparison with poorly characterised survival estimates for other patients with
      advanced disease. In this review I consider the evidence to date and conclude
      that a trial is needed.

PMID- 18065235
TI  - Conventional surgical repair and endovascular treatment of acute traumatic aortic
      rupture.
AB  - OBJECTIVE: Endoluminal aortic stent grafting offers a potentially less invasive
      alternative to open chest surgery, especially in patients with polytrauma. We
      compare the results of conventional surgical repair and endovascular treatment of
      traumatic aortic rupture. METHODS: Retrospectively, 74 patients with acute
      traumatic aortic rupture were analyzed. Most of the patients had a rupture
      limited to the isthmus, and severe associated injuries. Thirty-five patients (6
      female, 29 male, mean age 36 years) underwent surgical repair. Two patients were
      operated upon without cardiopulmonary bypass. In 39 patients (5 female, 34 male,
      mean age 36 years) thoracic endografts were implanted. The delay between trauma
      and treatment was comparable in the two groups. RESULTS: Hospital mortality was
      20% (7 of 35 patients) in the surgical group and 7.7% (3 of 39 patients) in the
      endovascular group. The most common cause of death in the surgical group was
      brain death in severe traumatic patients. Ten surgical complications occurred in
      5 patients: respiratory insufficiency (n=3), pulmonary infection (n=2), recurrent
      nerve palsy (n=2), repeat thoracotomy (n=2), and compartment syndrome (n=1). No
      patient in this group had paraplegia. Except for one case, which required
      conversion to conventional surgery, stent-graft implantation was successful in
      all cases, without peri-interventional complications or procedure-induced
      paraplegia. In 9 patients the left subclavian artery was covered with the device.
      Two patients underwent surgical repair 15 days and 4 months after endografting
      because of injury of the aortic wall by the stent and development of a spurious
      aneurysm, respectively. CONCLUSIONS: In the treatment of traumatic thoracic
      aortic rupture, the early outcome of patients treated with endovascular stent
      grafts appears to be better than that with conventional surgical repair. The new
      technique allows safe and successful repair of this life-threatening injury in
      the early phase of trauma management. How far this potential benefit is sustained
      in the long term remains unclear at present.

PMID- 18065236
TI  - Characterization of alternatively spliced isoforms of AMPA receptor subunits
      encoding truncated receptors.
AB  - Glutamate receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA)-type play an important role in synaptic plasticity and contribute to
      cell death under excitotoxic conditions. AMPA receptors form heterotetramers of
      four homologous subunits (GluR1-4), which exist in two functionally different
      isoforms, flip and flop, generated by alternative splicing. We identified
      transcripts for alternatively spliced isoforms of AMPA receptor subunits which
      lack both the flip and the flop exons, in hippocampal and retinal cultures. These
      transcripts originate AMPA receptor subunits lacking the flip/flop cassette, the
      fourth transmembrane domain and the intracellular C-terminus. Truncated GluR1
      associates with full-length GluR1 and exerts a dominant negative effect, giving
      rise to non-functional receptors. Moreover, truncated GluR1 reaches the cell
      surface, but is not efficiently targeted to the synapse. Hippocampal neuronal
      transfection with truncated GluR1 resulted in a significant reduction in
      apoptotic neuronal death triggered by toxic concentrations of glutamate.
      Furthermore, mRNA coding for the truncated subunits is consistently detected in
      some regions of the brain in epileptic rats and in hippocampal neurons submitted
      to toxic concentrations of glutamate. The existence of truncated AMPA receptor
      subunits may constitute an intrinsic neuroprotective mechanism.

PMID- 18065237
TI  - Expression of recombinant Bacillus licheniformis xylanase A in Pichia pastoris
      and xylooligosaccharides released from xylans by it.
AB  - The mature peptide of Bacillus licheniformis xylanase A (BlxA) was successfully
      expressed in Pichia pastoris under the control of AOX1 promoter. After 96-h 0.25%
      methanol induction, the activity of recombinant B. licheniformis xylanase A
      (reBlxA) in culture supernatant was 122.9 U/mg. Enzymatic properties assays
      showed that the optimum temperature and pH for reBlxA were 60 degrees C and pH
      6.0, respectively. When treated at 70 degrees C, pH 6.0 for 2 min, the residual
      activities of the reBlxA were 76%. Over 80% of reBlxA activity was retained after
      treatment of the enzyme by preincubation over a pH range of 5.0-9.0 for 1h at 25
      degrees C. High performance liquid chromatography (HPLC) analysis revealed that
      xylotriose (X3) was the main hydrolysis product released from birchwood xylan and
      wheat bran insoluble xylan by reBlxA. The mode of action studies showed that
      reBlxA was an endo-acting xylanase and xylobiose (X2), xylotriose, xylotetraose
      (X4), xylopentaose (X5), and xylohexaose (X6) could be hydrolyzed by it. This is
      the first report on the expression of reBlxA in yeast and on determining and
      quantifying the hydrolysis products released from xylans by reBlxA.

PMID- 18065239
TI  - A combinatorial approach to crystallization of PX-BAR unit of the human Sorting
      Nexin 9.
AB  - Sorting nexins (SNXs) form a family of proteins known to interact with endosomal
      vesicles and to regulate various steps of vesicle transport. Sorting Nexin 9
      (SNX9) is involved in the interface of endocytic, actin polymerizing, and signal
      transduction events in the cell. Here we report crystallization of the SNX9 PX
      BAR domain protein. Initially we used an ordinary protein construct design, and
      protein crystallization approaches resulted in obtaining granular crystal-like
      precipitation. SDS-PAGE and MS analysis of the crystal-like precipitation
      followed by protein construct optimization and using of macro seeding technique
      resulted in X-ray quality diffracting crystals. The crystals belonged to
      P2(1)2(1)2(1) space group (a=65.6 A, b=117.5 A, c=145.8 A) with two protein
      molecules per asymmetric unit. A complete SAD data set from Se-Methionine derived
      crystal (3.2 A) has been collected to solve the structure.

PMID- 18065238
TI  - Peripheral myelin of Xenopus laevis: role of electrostatic and hydrophobic
      interactions in membrane compaction.
AB  - P0 glycoprotein is the major structural protein of peripheral nerve myelin where
      it is thought to modulate inter-membrane adhesion at both the extracellular
      apposition, which is labile upon changes in pH and ionic strength, and the
      cytoplasmic apposition, which is resistant to such changes. Most studies on P0
      have focused on structure-function correlates in higher vertebrates. Here, we
      focused on its role in the structure and interactions of frog (Xenopus laevis)
      myelin, where it exists primarily in a dimeric form. As part of our study, we
      deduced the full sequence of X. laevis P0 (xP0) from its cDNA. The xP0 sequence
      was found to be similar to P0 sequences of higher vertebrates, suggesting that a
      common mechanism of PNS myelin compaction via P0 interaction might have emerged
      through evolution. As previously reported for mouse PNS myelin, a similar change
      of extracellular apposition in frog PNS myelin as a function of pH and ionic
      strength was observed, which can be explained by a conformational change of P0
      due to protonation-deprotonation of His52 at P0's putative adhesive interface. On
      the other hand, the cytoplasmic apposition in frog PNS myelin, like that in the
      mouse, remained unchanged at different pH and ionic strength. The contribution of
      hydrophobic interactions to stabilizing the cytoplasmic apposition was tested by
      incubating sciatic nerves with detergents. Dramatic expansion at the cytoplasmic
      apposition was observed for both frog and mouse, indicating a common hydrophobic
      nature at this apposition. Urea also expanded the cytoplasmic apposition of frog
      myelin likely owing to denaturation of P0. Removal of the fatty acids that
      attached to the single Cys residue in the cytoplasmic domain of P0 did not change
      PNS myelin structure of either frog or mouse, suggesting that the P0-attached
      fatty acyl chain does not play a significant role in PNS myelin compaction and
      stability. These results help clarify the present understanding of P0's adhesion
      role and the role of its acylation in compact PNS myelin.

PMID- 18065240
TI  - Cortisol response and immune-related effects of Atlantic salmon (Salmo salar
      Linnaeus) subjected to short- and long-term stress.
AB  - It is generally considered that stress causes decreased immune function in fish.
      In this study we examined in Atlantic salmon (Salmo salar Linnaeus) the effects
      of both short- (a single 15s out of water) and long-term (4 weeks of daily
      handling 15s out of water) stress on plasma cortisol (free and total) and glucose
      levels, expression of interleukin-1beta (IL-1beta) and survival of head kidney
      (HK) macrophages under culture with Aeromonas salmonicida. In the short-term
      study, samples were collected prior to the application of the stressor, and at 1,
      3, 6, 12 and 24h post stress. Free and total plasma cortisol levels and the
      percentage of free cortisol increased significantly in the stressed group at 1
      and 3h post stress. Plasma glucose levels were significantly higher than those of
      control fish at 1, 3 and 6h post stress. Constitutive expression of IL-1beta in
      macrophages isolated from head kidneys in stressed fish was significantly higher
      at 1 and 3h post stress. However, lipopolysaccharide (LPS) stimulated expression
      of IL-1beta in HK macrophages, exhibited significantly higher fold increases in
      unstressed fish compared to stressed fish. In the long-term study, with the
      exception of an increase in plasma glucose levels at 1 week, there were no
      significant differences in stress parameters between groups. There was a
      significantly higher constitutive IL-1beta expression in macrophages isolated
      from stressed fish over the first 2 weeks. At weeks 1, 2 and 3 the magnitude of
      IL-1beta response of isolated HK macrophages to LPS stimulation was reduced in
      >90% of the stressed fish. At 4 weeks there was no significant difference in
      inducible IL-1beta expression between the groups. Macrophages isolated from
      stressed fish also showed significantly decreased survival when exposed to A.
      salmonicida. This study shows a clear pattern from repeated handling stress,
      whereby effects on immune cells begin with increased constitutive expression of
      IL-1beta, followed by decreased stimulation of leucocytes by extracellular
      antigen, and finally decreased leukocyte survival when exposed to A. salmonicida.
      The implications of these changes in the immune system will be discussed with
      respect to the use of classical indicators of stress to predict possible effects
      on the immune system of fish.

PMID- 18065241
TI  - Direct assessment of qualia in a blindsight participant.
AB  - Experimenters generally infer whether participants have visual experiences based
      on metacognitive responses. We showed a well-studied blindsight participant, GY,
      several definitions of the term "qualia" and then questioned him about whether he
      felt or he experienced qualia in his normal and blind fields. We found, contrary
      to others who have used different methods for measuring qualia, that GY does not
      have qualia for stationary stimuli in his blind field. This novel method for
      directly assessing qualia embraces the idea that experiences should be related by
      the experiencer, not the experimenter.

PMID- 18065242
TI  - Blindsight is unlike normal conscious vision: evidence from an exclusion task.
AB  - We explored whether information processed subconsciously in blindsight is
      qualitatively different from normal conscious processing. On each trial the
      blindsight patient GY was presented with a square-wave grating either in an upper
      or lower quadrant of his visual field and was asked to report the opposite of its
      location (e.g. to say 'Up' if it was in the lower quadrant). We found that while
      GY was able to follow these exclusion instructions in his normal field, he tended
      to erroneously respond with the real location when the grating appeared in his
      blind field. Remarkably, his error rate actually increased with increasing
      grating contrast in his blind field. The interpretation of these results does not
      rely on subjective reports and thus cannot be criticized on the grounds that
      subjective reports are unreliable. We conclude that blindsight is unlike normal
      conscious vision.

PMID- 18065243
TI  - The impact of skull-stripping and radio-frequency bias correction on grey-matter
      segmentation for voxel-based morphometry.
AB  - This study evaluates the application of (i) skull-stripping methods (hybrid
      watershed algorithm (HWA), brain surface extractor (BSE) and brain-extraction
      tool (BET2)) and (ii) bias correction algorithms (nonparametric nonuniform
      intensity normalisation (N3), bias field corrector (BFC) and FMRIB's automated
      segmentation tool (FAST)) as pre-processing pipelines for the technique of voxel
      based morphometry (VBM) using statistical parametric mapping v.5 (SPM5). The
      pipelines were evaluated using a BrainWeb phantom, and those that performed
      consistently were further assessed using artificial-lesion masks applied to 10
      healthy controls compared to the original unlesioned scans, and finally, 20
      Alzheimer's disease (AD) patients versus 23 controls. In each case, pipelines
      were compared to each other and to those from default SPM5 methodology. The
      BET2+N3 pipeline was found to produce the least miswarping to template induced by
      real abnormalities, and performed consistently better than the other methods for
      the above experiments. Occasionally, the clusters of significant differences
      located close to the boundary were dragged out of the glass-brain projections --
      this could be corrected by adding background noise to low-probability voxels in
      the grey matter segments. This method was confirmed in a one-dimensional
      simulation and was preferable to threshold and explicit (simple) masking which
      excluded true abnormalities.

PMID- 18065244
TI  - Stesolid emergency treatment: cave social fear!
AB  - PURPOSE: To explore psychosocial effects of rectiole emergency treatment.
      METHODS: Children who had at some time been treated with Stesolid rectiole for
      seizure relief were questioned about feelings of shame in relation to this
      treatment and their expectation of bullying by peers who might be aware of it. In
      addition to parental shame, parental worries concerning their children's epilepsy
      were explored. Data from 39 patients (18 girls) aged 5-19 years were analysed.
      RESULTS: Of the children aged over seven, most girls (9/12), but not boys (1/6)
      reported to feeling a sense of shame. Children's shame was not related to
      parental shame, parental worries or seizure severity. A higher frequency of
      rectiole applications was related to a stronger expectation of being bullied.
      DISCUSSION AND CONCLUSION: Rectal emergency medication may elicit social fear,
      particularly in girls and if recurring it may (not solely in girls) elicit
      increased expectations of bullying.

PMID- 18065245
TI  - Ethanol state-dependent memory: involvement of dorsal hippocampal muscarinic and
      nicotinic receptors.
AB  - In the present study, the effects of bilateral injections of cholinergic agents
      into the hippocampal CA1 regions (intra-CA1) on ethanol state-dependent memory
      were examined in mice. A single-trial step-down passive avoidance task was used
      for the assessment of memory retention in adult male NMRI mice. Pre-training
      intraperitoneal injection (i.p.) of ethanol (0.25, 0.5 and 1g/kg) dose
      dependently induced impairment of memory retention. Pre-test administration of
      ethanol (0.5 and 1 g/kg, i.p.) induced state-dependent retrieval of the memory
      acquired under pre-training ethanol (1 g/kg, i.p.) influence. Pre-test intra-CA1
      injection of physostigmine (2.5 and 5 microg/mouse, intra-CA1) or nicotine (0.3
      and 0.5 microg/mouse, intra-CA1) improved pre-training ethanol (1g/kg)-induced
      retrieval impairment. Moreover, pre-test administration of physostigmine (2.5 and
      5 microg/mouse, intra-CA1) or nicotine (0.3 and 0.5 microg/mouse, intra-CA1) with
      an ineffective dose of ethanol (0.25 g/kg) significantly restored the retrieval
      and induced ethanol state-dependent memory. Pre-test intra-CA1 injection of the
      muscarinic receptor antagonist, atropine (4 and 8 microg/mouse, intra-CA1) or the
      nicotinic receptor antagonist, mecamylamine (2 and 4 microg/mouse, intra-CA1) 5
      min before the administration of ethanol (1g/kg, i.p.) dose dependently inhibited
      ethanol state-dependent memory. Pre-test intra-CA1 administration of
      physostigmine (0.5, 2.5 and 5 microg/mouse), atropine (2, 4 and 8 microg/mouse),
      nicotine (0.1, 0.3 and 0.5 microg/mouse) or mecamylamine (1, 2 and 4
      microg/mouse) alone cannot affect memory retention. These findings implicate the
      involvement of a dorsal hippocampal cholinergic mechanism in ethanol state
      dependent memory and also it can be concluded that there may be a cross-state
      dependency between ethanol and acetylcholine.

PMID- 18065246
TI  - Letter to the editor regarding "Fast track open aortic surgery: reduced post
      operative stay with a goal directed pathway". M.A. Murphy, T. Richards, C.
      Atkinson, J. Perkins and L.J. Hands. Eur J Vasc Endovasc Surg 2007;34:274-278.

PMID- 18065247
TI  - Aortoiliac reconstruction with allograft and kidney transplantation as a one
      stage procedure: long term results.
AB  - OBJECTIVES: An increasing number of aortoiliac lesions and abdominal aortic
      aneurysms occur in renal failure patients waiting for renal transplantation. The
      aim of our study was to assess long term results of simultaneous renal
      transplantation and surgical repair of aortoiliac lesions with arterial
      allografts. DESIGN: A retrospective observational study. PATIENTS AND METHODS:
      From October 1997 to June 2007, we performed simultaneous aortoiliac
      reconstructions using fresh arterial allografts and kidney transplantation in 14
      patients with chronic renal failure (men 9, women 5, mean age 53 years). The
      indication for vascular reconstruction was an asymptomatic abdominal aneurysm in
      6 patients or aortoiliac stenosis/occlusion in 8 patients. The median follow up
      period for the cohort was 55.5 months (range from 1 to 116 months). RESULTS:
      Three patients died during the follow up period. In none of them there was an
      allograft (neither arterial nor renal) related death. No signs of arterial grafts
      infection or aneurysmal formation and no need for secondary intervention
      (angioplasty and/or thrombolysis) of any arterial reconstruction was observed
      during the follow up period in any patient. The renal grafts failed in three
      patients. CONCLUSIONS: Our experience suggests that it is possible and safe to
      use arterial allografts in the treatment of arterial occlusive disease or
      abdominal aortic aneurysm simultaneously with renal transplantation.

PMID- 18065248
TI  - The transparent lens and cornea in the mouse and zebra fish eye.
AB  - The lens and cornea combine to form a single optical element in which
      transparency and refraction are the fundamental biophysical characteristics
      required for a functional visual system. Although lens and cornea have different
      cellular and extracellular specializations that contribute to transparency and
      refraction, their development is closely related. In the embryonic mouse, the
      developing cornea and lens separate early. In contrast, zebra fish lens and
      cornea remain connected during early development and the optical properties of
      the cornea and lens observed by slit lamp and quasielastic laser light scattering
      spectroscopy (QLS) are more similar in the zebra fish eye than in the mouse eye.
      Optical similarities between cornea and lens of zebra fish may be the result of
      similarities in the cellular development of the cornea and lens.

PMID- 18065249
TI  - Anomalous diffusion expressed through fractional order differential operators in
      the Bloch-Torrey equation.
AB  - Diffusion weighted MRI is used clinically to detect and characterize
      neurodegenerative, malignant and ischemic diseases. The correlation between
      developing pathology and localized diffusion relies on diffusion-weighted pulse
      sequences to probe biophysical models of molecular diffusion-typically exp[-(bD)]
      where D is the apparent diffusion coefficient (mm(2)/s) and b depends on the
      specific gradient pulse sequence parameters. Several recent studies have
      investigated the so-called anomalous diffusion stretched exponential model-exp[
      (bD)(alpha)], where alpha is a measure of tissue complexity that can be derived
      from fractal models of tissue structure. In this paper we propose an alternative
      derivation for the stretched exponential model using fractional order space and
      time derivatives. First, we consider the case where the spatial Laplacian in the
      Bloch-Torrey equation is generalized to incorporate a fractional order Brownian
      model of diffusivity. Second, we consider the case where the time derivative in
      the Bloch-Torrey equation is replaced by a Riemann-Liouville fractional order
      time derivative expressed in the Caputo form. Both cases revert to the classical
      results for integer order operations. Fractional order dynamics derived for the
      first case were observed to fit the signal attenuation in diffusion-weighted
      images obtained from Sephadex gels, human articular cartilage and human brain.
      Future developments of this approach may be useful for classifying anomalous
      diffusion in tissues with developing pathology.

PMID- 18065250
TI  - Control of jaw movements in two species of macropodines (Macropus eugenii and
      Macropus rufus).
AB  - The masticatory motor patterns of three tammar wallabies and two red kangaroos
      were determined by analyzing the pattern of electromyographic (EMG) activity of
      the jaw adductors and correlating it with lower jaw movements, as recorded by
      digital video and videoradiography. Transverse jaw movements were limited by the
      width of the upper incisal arcade. Molars engaged in food breakdown during two
      distinct occlusal phases characterized by abrupt changes in the direction of
      working-side hemimandible movement. Separate orthal (Phase I) and transverse
      (Phase II) trajectories were observed. The working-side lower jaw initially was
      drawn laterally by the balancing-side medial pterygoid and then orthally by
      overlapping activity in the balancing- and working-side temporalis and the
      balancing-side superficial masseter and medial pterygoid. Transverse movement
      occurred principally via the working-side medial pterygoid and superficial
      masseter. This pattern contrasted to that of placental herbivores, which are
      known to break down food when they move the working-side lower jaw transversely
      along a relatively longer linear path without changing direction during the power
      stroke. The placental trajectory results from overlapping activity in the working
      and balancing-side adductor muscles, suggesting that macropods and placental
      herbivores have modified the primitive masticatory motor pattern in different
      ways.

PMID- 18065251
TI  - Acute liver failure due to dengue virus infection.

PMID- 18065252
TI  - Recommendations of the French Society for Rheumatology regarding TNFalpha
      antagonist therapy in patients with ankylosing spondylitis or psoriatic
      arthritis: 2007 update.
AB  - OBJECTIVE: To update French Society for Rheumatology guidelines regarding the use
      of tumor necrosis factor alpha (TNFalpha) antagonists for treating patients with
      ankylosing spondylitis (AS) or psoriatic arthritis (PsA). METHODS: We used the
      method recommended by Shekelle et al. to update the original recommendations: a
      limited group of experts selected the items that required updating, the relevant
      literature was critically appraised, and the experts developed new wording for
      the recommendations, which was then subjected to internal and external
      validation. As with the original recommendations, three topics were addressed,
      namely, indications of TNFalpha antagonist therapy, treatment initiation, and
      treatment adjustment and follow-up. RESULTS: Four criteria should be used to
      evaluate the indication of TNFalpha antagonist therapy. First, the patient must
      have a definitive diagnosis of AS or PsA. Thus, patients with AS must meet
      modified New York criteria or exhibit characteristic involvement of the
      sacroiliac joints, spine, or peripheral sites documented by radiographs or
      computed tomography (structural damage) or by magnetic resonance imaging
      (inflammation). Patients with PsA must meet validated criteria such as the Moll
      and Wright or CASPAR criteria. The second criterion is active disease for more
      than 1month, with a BASDAI >or=4 in patients with predominantly axial disease or
      a tender/swollen joint count >or=3, and with a physician assessment of disease
      activity of >or=4/10. The third criterion is failure of at least three non
      steroidal anti-inflammatory drugs in patients with axial disease or of disease
      modifying antirheumatic drug (DMARD) therapy (methotrexate, salazopyrine, or
      leflunomide) in patients with peripheral disease. Fourth, the patient must be
      free of contraindications to TNFalpha antagonist therapy. Four recommendations
      pertain to the initiation of TNFalpha antagonist therapy: a workup should be
      performed prior to treatment initiation; there is no evidence that one TNFalpha
      antagonist is more effective than the others, so decisions about drug selection
      should be shared with the patient and guided by available safety data and the
      patient's profile; there is no proof that greater effectiveness can be achieved
      by routinely combining a conventional DMARD; and patients should receive regular
      standardized follow-up. The last four recommendations deal with adjusting
      TNFalpha antagonist therapy: the treatment objective is a 2-point or greater
      improvement in the BASDAI in patients with axial disease and a 30% or greater
      improvement in the tender/swollen joint counts in patients with peripheral
      disease; there is no evidence to support the introduction of DMARD therapy in non
      responders, who can be switched to another TNFalpha antagonist or, when on
      infliximab, given higher dosages or more closely spaced injections; patients who
      fail to tolerate one TNFalpha antagonist can be switched to another TNFalpha
      antagonist if allowed by the nature of the adverse event; and when a remission is
      achieved, reduction or discontinuation of concomitant anti-inflammatory therapy
      should be considered, followed in the event of a prolonged remission by a
      reduction in the dosage of the TNFalpha antagonist.

PMID- 18065253
TI  - Determination of the receiving range of sound field measurements in cavitating
      media.
AB  - Sound field measurements are widely used for the quantitative description of
      cavitation processes. For practical purposes it is important to know how local a
      sound field measurement information is, and therefore a technique is presented
      which allows the determination of the receiving range of such a measurement. The
      sound field is detected by two calibrated, similar hydrophones, mounted face to
      face in the cavitation cloud. The distance between the hydrophones is varied and
      the correlation between the two time-dependent signals is analyzed in the
      frequency domain defining a local parameter. The dependence of this parameter on
      the distance between the hydrophones describes the receiving range of a sound
      field measurement by means of a characteristic distance. The technique was
      applied to two different cavitation applications, and effective distances in the
      range 1-3mm were obtained. It is shown that the spatial resolution of a sound
      field measurement in a cavitation field is determined by the hydrophone size and
      does not depend on the cavitation conditions if at least a medium cavitation
      activity is provided.

PMID- 18065254
TI  - Ultrasound promoted asymmetric transfer hydrogenation of ketones using
      Ru(II)arene/amino alcohol catalyst system.
AB  - Asymmetric transfer hydrogenation of ketones using Ru(II)arene/amino alcohol
      catalyst system proceeds with significant rate enhancement by ultrasound
      promotion. Comparison of the silent reactions carried out at 25 degrees C with
      reactions under sonochemical activation at 25 degrees C clearly showed
      enhancement in catalytic activity by 5-10 times without significantly affecting
      the enantioselectivity.

PMID- 18065255
TI  - Sub-acute delayed failure of subthalamic DBS in Parkinson's disease: the role of
      micro-lesion effect.
AB  - OBJECTIVE: To study delayed failure after subthalamic nucleus (STN) deep brain
      stimulation in Parkinson's disease (PD) patients. METHODS: Out of 56 consecutive
      bilaterally STN-implanted PD patients, we selected subjects who, after initial
      clinical improvement (1 month after surgery), lost benefit (delayed failure, DF).
      RESULTS: Five patients developed sub-acutely severe gait disorders (DF). In 4/5
      DF patients, a micro-lesion effect, defined as improvement without stimulation,
      was observed; immediate post-operative MRI demonstrated electrode located above
      or behind to the STN. CONCLUSIONS: Patients presenting micro-lesion effect should
      be carefully monitored, as this phenomenon can mask electrodes misplacement and
      evolution in DF.

PMID- 18065256
TI  - A method for vector displacement estimation with ultrasound imaging and its
      application for thyroid nodular disease.
AB  - Ultrasound elastography is a promising imaging technique that can assist in
      diagnosis of thyroid cancer. However, the complexity of the tissue movements
      under freehand compression requires the use of a parametric displacement model
      and a specific estimation method adapted to sub-pixel motion. Therefore, the aim
      of this study was to develop a motion estimation method for ultrasound
      elastography and test its performances compared to a classical block matching
      technique. The proposed method, referred to as Bilinear Deformable Block Matching
      (BDBM), uses a bilinear model with eight parameters for controlling the local
      mesh deformation. In addition, a technique of motion initialization based on a
      triangle scan of the images adapted to ultrasound elastography is proposed. The
      BDBM method includes an iterative multi-scale process. This iterative approach is
      shown to decrease the absolute error of the displacement estimation by a factor
      of 1.4 when passing from 1 to 2 iterations. The method was tested on simulated
      images and the results show that absolute displacement estimation error was
      reduced by a factor of 4 compared to classical block matching. We applied the
      BDBM method on three experimental sets of data. In the first data set, a phantom
      designed for ultrasound elastography was used. The two other sets of data involve
      the thyroid gland and were acquired using freehand tissue compression by
      ultrasound probe of a clinical ultrasound scanner modified for research. A
      similarity measurement based on local cross-correlation shows that, for
      experimental data, the BDBM method outperforms the usual block matching.

PMID- 18065257
TI  - Growth coordination and the shoot epidermis.
AB  - Cell-cell communication is essential for growth and development of multicellular
      organisms. In higher plants, the shoot organs are derived from three clonally
      distinct cell layers present in the meristem. The role of the outermost L1 cell
      layer and its derived epidermis in coordinating growth of the inner-cell layers
      has long been debated. This question has been revisited recently using molecular
      tools to manipulate cell cycle progression or cell expansion, specifically in the
      epidermis. These studies conclude that cells in the epidermis both promote and
      restrict growth of the entire shoot by sending growth signals - either physical
      or chemical - to the inner layers.

PMID- 18065258
TI  - Trichlorfon-induced polyploidy and nondisjunction in mouse oocytes from preantral
      follicle culture.
AB  - Trichlorfon (TCF), an organophosphate insecticide and potent inhibitor of choline
      esterases, was previously shown to induce first meiotic nondisjunction and
      spindle aberrations in isolated, follicle cell-denuded mouse oocytes maturing in
      vitro. To explore dose-response and direct and indirect, potentially synergistic
      effects of TCF on the somatic cells and the oocyte within a follicle, we
      presently employed preantral follicle culture. 100 microg/ml TCF added at the
      time of hormonally stimulated resumption of meiosis of follicle cell-enclosed
      mouse oocytes, 16 h before in vitro ovulation, induced significant rises in first
      meiotic nondisjunction in oocytes from preantral follicle culture. Lower
      concentrations (6 microg/ml TCF) disturbed polar body formation. Nuclear
      maturation to meiosis II in absence of cytokinesis resulted in significant
      increases in polyploidy. Oocytes maturing in follicles in the presence of TCF had
      aberrant second meiotic spindles. Influences of TCF on somatic cell function were
      evident by reduced follicular mucification in vitro and deceased progesterone
      production. In contrast to TCF, acetylcholine (0.1-100 microM) increased
      progesterone production. The observations therefore suggest that TCF influences
      oocyte maturation and folliculogenesis directly and indirectly. High TCF is
      aneugenic at first meiotic division in oocytes, irrespective of the presence or
      absence of follicle cells. At lower concentrations TCF interferes with spindle
      formation, chromosome congression at meiosis II, and coordination of nuclear and
      cytoplasmic maturation, posing risks for second meiotic errors. The observations
      suggest that chronic TCF exposure during maturation in the follicle may
      predispose oocytes to the formation of chromosomally unbalanced preimplantation
      embryos after fertilization.

PMID- 18065259
TI  - A cleaner and simple spectrophotometric micro-fluidic procedure for copper
      determination using nitroso-R salt as chromogenic agent.
AB  - A cleaner and simple spectrophotometric method using microflow analysis (muFA)
      was performed. It consisted of a T-junction with microcoil on a polymethyl
      methacrylate (PMMA) chip which was fabricated by laser ablation and a molded
      polydimethylsiloxane (PDMS) as top plate. The fabricated PMMA chip was integrated
      with light emitting diode (LED) as light source and spectrometer as detector. The
      proposed device was applied to determining copper in water samples using nitroso
      R salt as chromogenic reagent at 495 nm. It was found that the proposed muFA
      system was with less reagents and samples consumption with tiny waste generation.
      The relative standard deviation (R.S.D.) was less than 2% (n=11) with the
      percentage recovery of 98.0+/-1.7% (n=7). The linear range for determination of
      copper in water samples was over the range of 0.05-3.0 microg mL(-1) with a
      correlation coefficient (r2) of 0.999. The limit of detection (3sigma) was 47 ng
      mL(-1) with a sample throughput of 30 h(-1).

PMID- 18065260
TI  - 2,5-di-[2-(3,5-bis(2-pyridylmethyl)amine -4-hydroxy-phenyl) ethylene] pyrazine
      zinc complex as fluorescent probe for labeling proteins.
AB  - The binding characteristics between 2,5-di-[2-(3,5-bis(2-pyridylmethyl)amine -4
      hydroxy-phenyl) ethylene] pyrazine (1) or its complex (1-Zn) and serum albumins
      were studied by fluorescence spectroscopy in pH 7.4 aqueous solution. 1-Zn
      emitted weak fluorescence at 580 nm in a pH 7.4 Tris-HCl buffer solution when
      excited at 435 nm, however, the fluorescence intensity increased upon addition of
      serum albumins with the blue shift of emission peak to 524 nm. The binding
      constants were estimated as 8.40 x 10(7) and 3.03 x 10(6)mol(-1)L for bovine
      serum albumin (BSA) and human serum albumin (HSA) respectively, and the number of
      binding sites was 1 for each. The quenching mechanism of fluorescence of serum
      albumins by 1-Zn was considered as a static quenching process. The binding
      distance between 1-Zn and serum albumins and the energy transfer efficiency were
      obtained based on the theory of Forester spectroscopy energy transfer. The effect
      of 1-Zn on the conformation of serum albumins was further analyzed using
      synchronous fluorescence spectrometry. The experiment results clearly showed that
      1-Zn is a highly sensitive protein sensor.

PMID- 18065261
TI  - Synthesis, crystal structure and optoelectronic properties of a new unsymmetrical
      photochromic diarylethene.
AB  - A new unsymmetrical photochromic diarylethene, 1-(2-methyl-5-phenyl-3-thienyl)-2
      [2-methyl-5-(3-trifluoromethylphenyl)-3-thienyl]perfluorocyclopentene (1a), was
      synthesized and its structure was determined by single-crystal X-ray diffraction
      analysis. Its optical and electrochemical properties, including photochromic
      reactivity both in solution and in the solid state (PMMA film and the single
      crystalline phase), fluorescence and electrochemical properties were investigated
      in detail. The compound showed excellent photochromism even in the single
      crystalline phase by photo-irradiation. In acetonitrile, the open-ring isomer of
      diarylethene 1 exhibited relatively strong fluorescence at 470 nm when excited at
      300 nm, and its emission intensity decreased along with the photochromism upon
      irradiation with 313 nm light. Its closed-ring isomer showed almost no
      fluorescence. The electrochemical properties of diarylethene were investigated by
      performing cyclic voltammetry experiment and its HOMO and LUMO energy level were
      calculated.

PMID- 18065262
TI  - Impact of influenza A virus neuraminidase mutations on the stability, activity,
      and sensibility of the neuraminidase to neuraminidase inhibitors.
AB  - BACKGROUND: The influenza neuraminidase plays a critical role in the spread of
      the influenza A and B viruses. Through the cleavage of terminal sialic acid from
      glycoconjugates, it facilitates the elution of progeny virions from infected
      cells and prevents their self-aggregation. OBJECTIVES: Our objective was to study
      the impact of mutations at framework sites not under direct selective pressure in
      the neuraminidase active site. STUDY DESIGN: In the A/Moscow/10/99 (H3N2) virus
      background, viruses containing mutations in NA framework residues (E119D, R156K,
      W178L, S179A, D198N, I222L, E227G, H274Y, E277G, N294D, and E425G) were
      constructed by reverse genetics. After several passages on MDCK cells,
      fluorimetric assays were conducted to assess the neuraminidase activity and
      sensibility to the neuraminidase inhibitors (IC50). RESULTS: Among the viruses
      detectable through the phenotypic tests, R156K, I222L, H274Y, N294D and E425G
      viruses presented a NA activity between 70% and 100% of the A/Moscow/10/99 wild
      type one. The D198N and the E119D mutations decreased seriously in NA activity
      compared to the wild-type (>10-fold). The I222L mutation reduced susceptibility
      to oseltamivir (18-fold). CONCLUSION: With the exception of one mutation,
      framework mutations on N2 background do not induce resistance. Nevertheless they
      tend to decrease slowly the sensitivity to one or the other inhibitors.

PMID- 18065263
TI  - Rapid molecular detection of influenza outbreaks in nursing homes.
AB  - BACKGROUND: Nursing home influenza outbreaks occur in spite of established
      vaccination programs, and require rapid and sensitive laboratory confirmation for
      timely intervention. OBJECTIVES: To evaluate diagnostic approaches for rapid
      confirmation of nursing home influenza outbreaks. STUDY DESIGN: Influenza virus
      real-time PCR and Directigen Flu A+B enzyme immunoassay were performed on
      nasopharyngeal swabs, nasopharyngeal washes and throat swabs collected from
      residents with clinical suspicion of influenza during seven probable nursing home
      outbreaks in 2004-2005 and 2005-2006. The efficacy of specimen sampling and
      transport management by Public Health Service outbreak team was evaluated.
      RESULTS: PCR detected influenza RNA in 80% (68/85) of specimens from 81% (38/47)
      residents, confirming six suspected outbreaks. Immunoassay sensitivity was
      highest on nasopharyngeal swabs (38%; 11/29) with a positive predictive value of
      100% compared to PCR. Nasopharyngeal swabs were equally sensitive to
      nasopharyngeal washes by PCR. Nasopharyngeal wash sampling appeared unpractical
      due to common underlying disability of residents. Outbreak team support was
      associated with a shorter time to PCR diagnosis compared to outbreaks with no
      logistical support (mean, 28.2h vs. 84h; P=0.05). CONCLUSIONS: Influenza real
      time PCR on nasopharyngeal swabs, obtained by Public Health Service outbreak
      teams, enabled rapid and sensitive confirmation of nursing home influenza
      outbreaks.

PMID- 18065264
TI  - High-fidelity recording of brain activity in the extremely preterm babies:
      feasibility study in the incubator.
AB  - OBJECTIVE: To develop an electrode cap with high number of electrodes for
      recording very small preterm babies, to assess the physiological stress imposed
      by the application of this cap on babies, and to estimate what added information
      could be potentially obtained with more electrodes in this age group. METHODS: We
      recruited eleven extremely small preterm babies (conceptional age 25-29 weeks) to
      record their EEG with a custom-tailored high-density EEG cap (20 channels),
      coupled with a Full-band EEG amplifier. Physiological stress caused by the cap
      placement was assessed by recording heart rate and arterial oxygen saturation
      before and during EEG cap placement, as well as before and during a routine care
      procedure of the given baby. The quality of novel information obtained with this
      system was assessed by comparing the full signal to a set of EEG signals where we
      deliberately distorted and omitted major signal components to make it appear as
      in the conventional EEG systems. RESULTS: The changes in heart rate or oxygen
      saturation caused by the cap placement are fully comparable to the changes seen
      after any normal care procedure in the same baby. Our recordings did also reveal
      that brain activity in the small premies is highly focal, and often confined to
      only one or two electrodes. Hence it cannot be pertinently localized with the
      currently used low number of recording electrodes. Moreover, recordings from
      babies with focal intracerebral hemorrhages showed that changes after vascular
      insults are clearly more prominent and hence easier to detect visually from
      multichannel recordings. CONCLUSIONS: Recording of high-fidelity EEG (high
      density caps and FbEEG system) is practical in the incubator environment, and the
      application of a proper EEG cap is not more stressful to the baby than a routine
      care procedure. Moreover, these achievable amendments in the recording system
      seem to disclose major physiological and pathological signal components in the as
      yet poorly explored patient group. SIGNIFICANCE: Introduction of a technically
      feasible and physically gentle enough EEG recording system will enable further
      development of clinical neurophysiological understanding, as well as the design
      of pertinent brain monitors, which is urgently needed in these patients.

PMID- 18065265
TI  - Motor cortex cholinergic dysfunction in CADASIL: a transcranial magnetic
      demonstration.
AB  - OBJECTIVE: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leukoencephalopathy (CADASIL) is a hereditary small vessel disease responsible
      for an early onset cognitive impairment. Aim of our study was to test the
      cortical cholinergic innervation in CADASIL by short latency afferent inhibition
      (SAI) technique. METHODS: We applied SAI in ten CADASIL patients and in ten age
      matched normal controls. SAI is a phenomenon observed on motor evoked potential
      when transcranial magnetic stimulation is delivered after a time ranging from 2
      to 8 ms longer than the time needed by the peripheral nerve afferent input to
      reach the somatosensory cortex. RESULTS: The amount of short latency afferent
      inhibition was significantly smaller in CADASIL patients than in controls (79.5+/
      21.7% Vs 42.7+/-14.1% of test size; p<0.001, two tailed Mann-Whitney test). The
      mean resting motor threshold (RMT) was significantly lower in CADASIL patients
      than in controls (49.4+/-14.4% Vs 65.6+/-15.4%; p=0.02). CONCLUSIONS: We
      demonstrated by SAI technique a central cholinergic impairment in CADASIL.
      SIGNIFICANCE: SAI could be used to evaluate the cholinergic dysfunction and
      potentially the efficacy of cholinomimetic therapy in CADASIL.

PMID- 18065266
TI  - Quantification and visualisation of differences between two motor tasks based on
      energy density maps for brain-computer interface applications.
AB  - OBJECTIVE: To determine the most discriminative features for a brain-computer
      interface (BCI) system based on statistically significant differences between two
      energy density maps calculated from EEG signals during two different motor tasks.
      METHODS: EEG was recorded in ten healthy volunteers while performing different
      cue based, 3s sustained, real and imaginary right hand movements. Energy density
      maps were calculated over fixed 240 ms and 2 Hz time-frequency windows (called
      resels) for each movement and statistically significant resels were determined.
      After that, normalised energy values of the statistically significant resels were
      compared between two real as well as between two imaginary movements using a
      parametric test. RESULTS: The largest differences between energy density maps
      between two motor tasks were noticed on electrode location Cp3 in the higher
      alpha and the beta bands (i.e., 12-30 Hz), for both real and imaginary movements.
      The method reduced a total number of discriminative features between two motor
      tasks to fewer than 2% for the imaginary and fewer than 3% for the real movements
      on the electrode location Cp3. CONCLUSIONS: The method can be used for
      visualisation and feature extraction for BCI and other applications where event
      related desynchronisation/synchronisation (ERD/ERS) maps should be compared.
      SIGNIFICANCE: If a reliable on-line classification of imaginary movements of the
      same limb would be achieved it could be combined with classification of movements
      of different parts of the body. That would increase a number of separable classes
      of a BCI system, thereby providing a larger number of command signals to control
      the external devises such as computers and robotic devices.

PMID- 18065269
TI  - Meeting report: Tuberculosis research in China; a historic meeting; China-Japan
      US Tuberculosis International Seminar and US-Japan Cooperative Medical Science
      Program 42nd Tuberculosis and Leprosy Research Conference, 2007.

PMID- 18065267
TI  - EEG of chronic marijuana users during abstinence: relationship to years of
      marijuana use, cerebral blood flow and thyroid function.
AB  - OBJECTIVE: Marijuana abuse is associated with neurological changes including
      increases in frontal EEG alpha during abstinence. Research is needed to assess to
      what extent these EEG patterns are indicative of cerebral perfusion deficits.
      METHODS: We recorded the resting eyes closed EEG of 75 abstinent marijuana users
      and 33 control subjects. Fifty-six marijuana users used marijuana for less than
      eight years and 19 used for eight years or more. The EEG evaluation occurred
      within 72h of admission to an inpatient unit. Fifty-nine marijuana users remained
      abstinent for a month and were tested twice. Supplemental psychological and
      physiological data were also collected. RESULTS: Log alpha2 and beta2 power at
      posterior sites were significantly lower for the marijuana abusers that used
      eight years or more than the other marijuana abusers and the control subjects.
      These EEG changes continued for the month of abstinence. The marijuana users who
      used marijuana for more than eight years, also, had lower heart rates and thyroid
      function (T4) compared to the other marijuana users and the control subjects.
      CONCLUSIONS: Chronic marijuana use was also associated with reduced EEG power in
      alpha and beta bands at posterior sites. These reductions in EEG power appear to
      be related to cerebral perfusion deficits and/or thyroid function in marijuana
      abusers. SIGNIFICANCE: Our results suggest EEG, cerebral blood flow velocity,
      cardiovascular and thyroid function alterations in marijuana abuser with an
      extended period of use. These alterations reflect under arousal in these systems.

PMID- 18065270
TI  - The validity of the Child Behavior Checklist for children with epilepsy.
AB  - The validity of the Child Behavior Checklist (CBCL) for patients with epilepsy
      has been questioned, because several items may reflect seizure semiology rather
      than habitual behavior. This study compared a standard version of the CBCL with
      an adjusted version that excluded those ambiguous items. Participants were 58
      pediatric patients with epilepsy who were assessed preoperatively and 1 year
      after successful surgical treatment. Before surgery, the adjusted version
      indicated significantly lower values for the scales Attention Problems, Thought
      Problems, and Total Problems than the standard version. After surgery, the
      difference between the standard and adjusted versions and the scores for the
      ambiguous items were unchanged, although all patients were completely seizure
      free at that time. Elevated scores on the ambiguous items thus probably reflect
      real behavioral problems and are not due to confusion with seizure semiology. The
      results support the CBCL as a valid assessment tool in children with epilepsy.

PMID- 18065271
TI  - Attention-deficit/hyperactivity disorder in pediatric patients with epilepsy:
      review of pharmacological treatment.
AB  - Attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy is a
      common source of impairment. Based on review of Medline indexed articles, meeting
      abstracts, and data requested from drug manufacturers, a summary of evidence that
      might guide treatment and research is presented. Methylphenidate (MPH) has shown
      high response rates and no increase in seizures in small trials. However, low
      baseline seizure rates, small numbers of subjects, and short observation periods
      limit the power of these studies to detect increases in seizure risk. Although
      longer-term effects of MPH and its effects in children with frequent seizures
      need to be studied, the evidence available at this time best supports use of MPH
      for the treatment of ADHD not amenable to changes in antiepileptic drugs or
      improvements in seizure control. This treatment should be part of a
      biopsychosocial approach. Other agents show promise. Preclinical, retrospective
      and open-label studies on amphetamines and atomoxetine support undertaking
      randomized controlled studies of these agents in patients with ADHD plus
      epilepsy. In contrast, additional data on guanfacine and modafinil should be
      gathered before undertaking randomized controlled studies with these agents.

PMID- 18065272
TI  - An in vivo and in vitro potential of Indian ayurvedic herbal formulation Triphala
      on experimental gouty arthritis in mice.
AB  - In the present study, we have investigated the efficacy of Indian ayurvedic
      herbal formulation Triphala on monosodium urate crystal-induced inflammation in
      mice; an experimental model for gouty arthritis and compared it with that of the
      non-steroidal anti-inflammatory drug, Indomethacin. The anti-arthritic effect of
      Triphala was evaluated by measuring changes in the paw volume, lysosomal enzyme
      activities, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF
      alpha in control and monosodium urate crystal-induced mice. The levels of beta
      glucuronidase and lactate dehydrogenase were also measured in monosodium urate
      crystal-incubated polymorphonuclear leucocytes (PMNL). Triphala treatment (1
      gm/kg/b.w. orally) significantly inhibited the paw volume and the levels of
      lysosomal enzymes, lipid peroxidation and inflammatory mediator tumour necrosis
      factor-alpha; however the anti-oxidant status was found to be increased in
      plasma, liver and spleen of monosodium urate crystal-induced mice when compared
      to control mice. In addition, beta-glucuronidase and lactate dehydrogenase level
      were reduced in Triphala (100 microg/ml) treated monosodium urate crystal
      incubated polymorphonuclear leucocytes. In conclusion, the results obtained
      clearly indicated that Triphala exerted a strong anti-inflammatory effect against
      gouty arthritis.

PMID- 18065273
TI  - Insulin resistance and incident gallbladder disease in pregnancy.
AB  - BACKGROUND & AIMS: Insulin resistance is associated with prevalent gallstones,
      but its effect on initial gallstone formation is not well-understood. METHODS: We
      conducted a nested case-control study to examine whether insulin resistance is a
      risk factor for initial gallbladder sludge and stone formation during pregnancy.
      Cases were 205 women with new gallbladder sludge and stones during pregnancy and
      the early postpartum. Controls were 443 randomly selected women without sludge or
      stones during pregnancy. Gallbladder ultrasounds were obtained during each
      trimester and at 4-6 weeks post partum. Fasting serum glucose, lipids, and
      insulin were measured at 26-28 weeks gestation. Insulin resistance was measured
      by the homeostasis model. Logistic regression was used to identify independent
      risk factors for gallstone formation. RESULTS: Insulin resistance was
      significantly greater in cases than in controls on univariate analysis (P <
      .001). Pre-pregnancy body mass index was strongly associated with gallstone
      formation on univariate analysis (P < .001), but this association was diminished
      after adjusting for insulin resistance (P = .01). On multivariate analysis,
      insulin resistance was significantly associated with gallstone formation (P =
      .004), even after adjustment for pre-pregnancy body mass index and other
      confounding factors including high-density lipoprotein cholesterol and physical
      activity. This association was strongest in women with pre-pregnancy body mass
      index <30 kg/m(2). CONCLUSIONS: Insulin resistance is a risk factor for incident
      gallbladder sludge and stones during pregnancy, even after adjustment for body
      mass index. Insulin resistance might represent a causal link between obesity and
      overweight and gallstones.

PMID- 18065274
TI  - Impact of orthotopic liver transplant for primary sclerosing cholangitis on
      chronic antibiotic refractory pouchitis.
AB  - BACKGROUND & AIMS: The effect of orthotopic liver transplantation (OLT) for
      primary sclerosing cholangitis (PSC) and post-OLT immunosuppression on the
      disease course of pouchitis is not clear. The aims of this study were to compare
      the frequency of chronic antibiotic-refractory pouchitis (CARP) in PSC patients
      with or without OLT and to assess potential risk factors for CARP in these
      patients. METHODS: Ulcerative colitis patients with PSC and ileal pouch-anal
      anastomosis (IPAA) with or without OLT identified from our prospectively
      maintained pouch database were analyzed. CARP was diagnosed based on persistent
      symptomatic pouchitis after a 4-week single- or dual-antibiotic therapy. RESULTS:
      A total of 63 PSC/IPAA patients were studied, including 19 patients with OLT and
      44 patients without OLT. Fifty patients (79.4%) had CARP. In both univariable and
      multivariable analyses (adjusting for OLT status), none of the variables studied
      was associated significantly with CARP (P > .20). All 7 patients (100%) with IPAA
      then-OLT were diagnosed as having CARP, of whom 4 developed CARP before OLT,
      which persisted after OLT, and 3 had CARP after OLT. Of 12 patients with OLT-then
      IPAA, 7 (58.3%) developed CARP. The frequency of CARP in OLT-then-IPAA was
      statistically significantly lower than that in IPAA-then-OLT (58.3% vs 100%; P =
      .047). CONCLUSIONS: CARP is common in patients with ulcerative colitis and PSC.
      OLT in these patients may not affect the frequency of CARP in general and appears
      not to alter the disease course of pre-existing CARP. However, in a subset of
      patients, OLT might reduce the risk for the development of de novo CARP.

PMID- 18065275
TI  - Small bowel obstruction produced by a phytobezoar.

PMID- 18065276
TI  - Multiphoton imaging can be used for microscopic examination of intact human
      gastrointestinal mucosa ex vivo.
AB  - BACKGROUND & AIMS: The ability to observe cellular and subcellular detail during
      routine endoscopy is a major goal in the development of new endoscopic imaging
      techniques. Multiphoton microscopy, which relies on nonlinear infrared optical
      processes, has the potential to identify cellular details by excitation of
      endogenous fluorescent molecules. We examined the feasibility of using
      multiphoton microscopy to characterize mucosal histology in the human
      gastrointestinal tract. METHODS: A multiphoton microscope was used to determine
      the optimal excitation wavelength for examination of gastrointestinal mucosa.
      Fresh, unfixed, and unstained biopsy specimens obtained during routine endoscopy
      in human subjects then were examined by confocal microscopy and multiphoton
      microscopy. Multiphoton images also were compared with standard H&E images
      obtained from paired biopsy specimens. A prototype miniaturized multiphoton probe
      was used to examine intact rat colon. RESULTS: Peak multiphoton autofluorescence
      intensity was detected in mucosa excited at 735 nm. Multiphoton microscopic
      examination of unstained biopsy specimens revealed improved cellular detail
      relative to either unstained or stained specimens examined by confocal imaging.
      Resolution of structures such as epithelial nuclei, goblet cells, and
      interstitial fibers and cells was comparable with what was obtained using
      standard H&E histology. Similar findings were observed when using a prototype
      miniaturized multiphoton probe. CONCLUSIONS: Multiphoton microscopy can be used
      to examine gastrointestinal mucosa at the cellular level, without the need for
      fluorescent dyes. The construction of a multiphoton endomicroscope therefore
      could provide a practical means of performing virtual biopsies during the course
      of routine endoscopy, with advantages over currently available endomicroscopy
      technologies.

PMID- 18065277
TI  - Cecal insertion and withdrawal times with wide-angle versus standard
      colonoscopes: a randomized controlled trial.
AB  - BACKGROUND & AIMS: The aim of this study was to see if a 170 degrees angle of
      view (wide angle [WA]) colonoscope allowed faster withdrawal without decreasing
      adenoma detection. METHODS: Eight colonoscopists at 2 institutions participated
      in the study. Patients were randomized so that each colonoscopist performed 50%
      of the exams with a 160 series (140 degrees angle of view; standard [ST])
      colonoscope and 50% with a prototype 160 series colonoscope with a 170 degrees
      angle of view (WA instrument). Insertion and withdrawal times and number of
      polyps detected were recorded. Endoscopists were asked to withdraw as quickly as
      they could carefully complete the exams. Analysis of variance was done to compare
      insertion and withdrawal times and number of polyps detected. Time to perform
      biopsy, polypectomy, and cleaning was subtracted using a stopwatch. RESULTS: A
      total of 710 procedures were performed, 355 with ST and 355 with WA colonoscope.
      The mean insertion time was similar. The mean withdrawal time (absent time for
      suctioning, washing, etc.) with the WA colonoscope was 4.9 min which was shorter
      (4.9 vs 5.4 min; P = .0001) overall and for three individual endoscopists (P =
      .0001, P = .01, and P = .03). There was no difference in the mean number of
      adenomas detected per colonoscopy with ST (0.6) compared to WA (0.5) (P = .12).
      Two of the three endoscopists with shorter withdrawal times with WA had
      numerically higher detection rates with WA. CONCLUSIONS: The WA colonoscope is
      associated with a reduction in withdrawal time without compromising adenoma
      detection. However, this effect is operator dependent and the overall impact of
      wide-angle optics in this study was minor.

PMID- 18065278
TI  - Bispectral index monitoring of conscious sedation with the combination of
      meperidine and midazolam during endoscopy.
AB  - background & aims: Current practice guidelines strongly recommend differentiation
      of deep from moderate sedation during endoscopy. Standard methods of sedation
      monitoring are labor-intense. Bispectral index monitoring (BIS) is widely used
      during anesthesia, but its benefits during conscious sedation are controversial.
      Thus, we performed a prospective observational study to assess its ability for
      detecting deep sedation during endoscopy. METHODS: Patients presenting for
      elective outpatient endoscopy were monitored simultaneously with the Modified
      Observer's Assessment of Alertness and Sedation (MOAA/S) and BIS. A combination
      of a narcotic and benzodiazepine was used, with the target being moderate
      sedation and analgesia. Deep sedation was defined by MOAA/S score of 1-2 and BIS
      score of <or=75. With MOAA/S as the reference standard, the accuracy of BIS for
      detecting deep sedation was evaluated. RESULTS: A total of 775 simultaneous
      observations of BIS and MOAA/S scores were recorded on 76 patients. Deep
      sedation, defined by MOAA/S and BIS, was seen in 204 (26%) and 92 (12%)
      observations, respectively. BIS correlated poorly with deep sedation (rho, -0.02;
      95% confidence interval [CI], -0.16-0.12). The sensitivity, specificity, and
      positive and negative predictive values (95% CI) for detecting deep sedation were
      29.6 (23.4-36.3), 94.9 (92.8-96.6), 68.2 (57.4-77.7), and 78.6 (75.3-81.7),
      respectively. CONCLUSIONS: BIS has a low accuracy for detecting deep sedation as
      a result of a considerable overlap of scores across the sedation levels. Further
      refinements in BIS are needed to differentiate deep from moderate sedation for
      future studies on conscious sedation.

PMID- 18065279
TI  - Interventricular mechanical dyssynchrony: a novel marker of cardiac events in
      Brugada syndrome.
AB  - BACKGROUND: Risk stratification in Brugada syndrome is controversial, especially
      in asymptomatic individuals. OBJECTIVE: The purpose of this study was to evaluate
      tissue Doppler echocardiography in risk stratification of Brugada syndrome.
      METHODS: Patients with Brugada ECG pattern were enrolled in the study. Left
      ventricular (LV) preejection period was defined as the time interval between
      onset of the QRS complex and onset of LV lateral wall systolic wave. Right
      ventricular (RV) preejection period was defined as the time interval between
      onset of the QRS complex and onset of RV lateral wall systolic wave. Delay in
      onset of contraction between RV and LV was defined as RV preejection time - LV
      preejection time [PET((RV-LV))]. RESULTS: Type 1, 2, and 3 Brugada ECG pattern
      was found in 30, 56, and 31 patients, respectively. PET((RV-LV)) was
      significantly greater in type 1 Brugada patients (39.2 +/- 3.2 ms) compared with
      type 2 (5 +/- 0.3 ms) and 3 (5 +/- 0.4 ms) Brugada patients as well as controls
      (4.6 +/- 0.3 ms, P <.01 for all comparisons). Among type 1 Brugada patients,
      PET((RV-LV)) was significantly greater in patients who had previous cardiac
      events compared with asymptomatic subjects (48.2 +/- 4.3 ms vs 29.5 +/- 3.6 ms, P
      <.05). In the presence of type 1 Brugada ECG pattern, PET((RV-LV)) > or =40 ms
      identifies patients likely to have cardiac events, with 85.7% sensitivity and
      93.7% specificity. CONCLUSION: PET((RV-LV)) is an important risk indicator for
      Brugada syndrome.

PMID- 18065280
TI  - Unmasking concealed long QT syndrome.

PMID- 18065281
TI  - Cardiac resynchronization therapy from cell to bedside: the time has come to
      focus more on the cell.

PMID- 18065282
TI  - Stretch the heart: get memory.

PMID- 18065283
TI  - Alcohol ablation for ventricular tachycardia: a distillation of modern cases.

PMID- 18065284
TI  - Image fusion shows the role of incomplete ablation lines in creating a substrate
      for left atrial flutter occurring after atrial fibrillation ablation.

PMID- 18065285
TI  - Pacemaker/implantable cardioverter-defibrillator problem: right ventricular lead
      missensing in a biventricular implantable cardioverter-defibrillator.

PMID- 18065286
TI  - Metamorphosis of a tachycardia: what is the mechanism?

PMID- 18065287
TI  - Gout and the postoperative bariatric surgery patient.

PMID- 18065288
TI  - Revision of jejunoileal bypass to Roux-en-Y gastric bypass: technical
      considerations and outcomes from 2 cases.

PMID- 18065289
TI  - Does diabetes affect weight loss after gastric bypass?
AB  - BACKGROUND: Weight loss in diabetics improves glycemic control. We investigated
      whether diabetes mellitus (DM) adversely affects postgastric bypass weight loss.
      METHODS: Our database was queried for the demographics and outcomes of patients
      with and without DM who had undergone gastric bypass surgery. DM was subdivided
      by severity: diet-controlled, oral hypoglycemic agents, and insulin. RESULTS: Of
      the 3193 patients, 655 (20%) had DM. The DM group was older (45.8 +/- 10.4 yr
      versus 39.1 +/- 9.9 yr, P <.0001), with more co-morbidities: hypertension (70.5%
      versus 44.2%, P <.0001), sleep apnea (36.7% versus 26.1%, P <.0001), and venous
      stasis (5.6% versus 2.6%, P <.0001). More men had DM (25.6% versus 19.3%, P =
      .0006). The age-adjusted, preoperative weight, and body mass index were equal. A
      direct relationship was found between DM severity and age, weight, and co
      morbidities. At 1 year, the DM group had a lower percentage of excess weight loss
      (60.8% +/- 16.6% versus 67.6% +/- 16.7%, P <.0001) and greater body mass index
      (34.2 +/- 7.1 kg/m(2) versus 32.3 +/- 7.2 kg/m(2), P <.0001). The percentage of
      excess weight loss was 67.6% for those without DM, 63.5% for those with diet
      controlled DM, 60.5% for those with DM controlled by oral hypoglycemic agents,
      and 57.5% for those requiring insulin. DM resolved in 89.8% of those with diet
      controlled DM, 82.7% of those taking oral hypoglycemic medication, and 53.3% of
      those requiring insulin. Hypertension resolution was greatest in patients without
      DM (74.4% versus 63.5%, P <.0001). CONCLUSION: The results of our study have
      shown that those with DM typically have more co-morbidities, despite having no
      difference in preoperative weight compared with those without DM. Despite the
      lower weight loss, those with DM had significant resolution of their DM and
      hypertension and should not be deterred from undergoing gastric bypass surgery.

PMID- 18065290
TI  - Revisional bariatric surgery for failed restrictive procedures.
AB  - BACKGROUND: Revisional bariatric surgery is increasing in frequency, but the
      morbidity and efficacy have not been well defined. The primary aim of this study
      was to determine the clinical efficacy with respect to weight loss, and
      associated morbidity, of revisional bariatric surgery in an academic university
      hospital bariatric surgery program. METHODS: A retrospective review of all
      patients who underwent revisional bariatric surgery for failed primary
      restrictive procedures, including gastroplasty and gastric bypass, but not
      including gastric banding or malabsorptive procedures, during a 10-year period at
      a single university hospital was performed. The perioperative morbidity and long
      term weight loss and clinical results were determined from the medical charts.
      RESULTS: A total of 41 patients met the inclusion criteria. The primary bariatric
      procedures included vertical banded gastroplasty in 20 and Roux-en-Y gastric
      bypass in 21. The indications for revisional surgery included poor weight loss,
      weight regain, and various technical problems, including anastomotic stenosis and
      ulcer. The major morbidity rate was 17%. No patients died. The weight loss
      results varied depending on the indication for the revisional surgery and
      reoperative solution applied. The resolution of technical problems was achieved
      in all patients. CONCLUSION: Revisional bariatric surgery can be performed with
      minimal mortality, albeit significant morbidity. The efficacy with respect to
      weight loss appeared acceptable, although the results were not as good as those
      after primary bariatric surgery. The analysis of patient subsets stratified by
      surgical history and revisional strategy provided important insights into the
      mechanisms of failure and efficacy of different revisional strategies.

PMID- 18065291
TI  - Recurrent pancreatitis as only presenting symptom of intermittent small bowel
      obstruction after biliopancreatic diversion with duodenal switch.

PMID- 18065292
TI  - Gouty attacks occur frequently in postoperative gastric bypass patients.
AB  - BACKGROUND: Both obesity and surgery are known risk factors for instigating gouty
      attacks. We describe the incidence and management of postoperative gouty attacks
      after bariatric surgery. METHODS: We performed a retrospective, multi
      institutional review of 411 consecutive laparoscopic gastric bypass patients and
      identified all patients with postoperative gouty attacks. RESULTS: Of the 411
      patients reviewed, 21 (5.1%) had had a previous diagnosis of gout. Of these 21
      patients, 7 (33.3%) had had an acute attack postoperatively. No patient who had
      never had a preoperative episode developed gout. In 4 of the 7 (57.1%) patients,
      the attack was severe enough to require treatment with corticosteroids.
      Monoarticular attacks occurred in 5 (71.4%) of the 7 patients, and polyarticular
      attacks occurred in 2 (28.6%). The joints involved included the toes, ankles, and
      wrists. One patient presented with cervical gout and developed polyarticular gout
      that required a significant rehabilitation stay. CONCLUSION: The morbidity of
      postoperative gouty attacks in bariatric surgery patients is significant.
      Patients with a history of gout should given prophylactic treatment and closely
      monitored.

PMID- 18065293
TI  - Safety and efficacy of intravascular ultrasound-guided inferior vena cava filter
      in super obese bariatric patients.
AB  - BACKGROUND: The morbidly obese (body mass index >40 kg/m(2)) are at significant
      risk of postoperative venous thromboembolism (VTE). Pulmonary embolism is the
      leading cause of death after Roux-en-Y gastric bypass, approximating .5%. Because
      of the technical limitations with fluoroscopy and table weight limits, it has
      been our practice at our university-based bariatric center to offer intravascular
      ultrasound (IVUS)-guided inferior vena cava filter (IVCF) placement at Roux-en-Y
      gastric bypass to patients with a history of VTE, hypercoagulable state, or
      profound immobility. METHODS: The hospital and outpatient records of all 594
      patients who underwent Roux-en-Y gastric bypass from January 1, 2004 to October
      31, 2006 were reviewed. The patients who had undergone concurrent IVUS-guided
      IVCF placement were selected. The co-morbidities, outcomes, and complications
      were recorded. RESULTS: Of the 594 patients, 31 (mean body mass index 71.2 +/-
      2.96 kg/m(2)) had undergone concurrent IVUS-guided IVCF placement. The
      indications included a history of VTE (n = 5), a known hypercoagulable state (n =
      2), and profound immobility (n = 25). The technical success rate was 96.8%. One
      filter was malpositioned in the iliac vein. No catheter site complications
      occurred. A ventilation/perfusion scan and computed tomography scan each detected
      pulmonary embolism in 2 surviving patients within 2 months postoperatively. Two
      patients died, 1 on postoperative day 8 and 1 on postoperative day 15 (6.4%). The
      mean follow-up time was 262.8 +/- 37.3 days. Autopsy excluded VTE or IVCF-related
      issues as the cause of death in both patients. CONCLUSION: These results suggest
      the efficacy of IVUS-guided IVCF placement in preventing mortality from pulmonary
      embolism in high-risk bariatric patients. IVUS-guided IVCF placement can be
      safely performed with an excellent success rate in high-risk patients who would
      not otherwise be candidates for intervention because of the technical limitations
      of fluoroscopy.

PMID- 18065294
TI  - Selective approach to use of upper gastroesophageal imaging study after
      laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: Many institutions routinely perform upper gastroesophageal imaging
      (UGI) studies on their laparoscopic Roux-en-Y gastric bypass (LRYGB) patients
      after surgery. We had routinely studied our patients with UGI on postoperative
      day 1 to rule out an anastomotic leak or obstruction, until recently when we
      abandoned this practice. As previously reported, we found that routine UGI did
      not contribute significantly to patient care. The purpose of this study was to
      determine whether patient outcomes were affected by this change in protocol.
      METHODS: From March 2004 to September 2005, 508 LRYGB cases were performed at our
      institution. Linear cutting staplers were used to create both the
      gastrojejunostomy and the jejunojejunostomy. In each case, the Roux limb was
      brought up in an antecolic, antegastric configuration. Before changing our
      protocol, 194 LRYGB cases were performed, and each patient underwent a routine
      UGI study (group 1). After abandoning this practice, 314 LRYGB cases were
      performed (group 2), and an UGI study was obtained only if clinical indicators
      (e.g., tachypnea, tachycardia, nausea, vomiting, low urine output, and/or
      abdominal pain) were present. The patient demographics, including gender, age,
      body mass index, length of hospital stay, and complications were recorded in our
      bariatric database and reviewed retrospectively. RESULTS: A postoperative UGI
      study was obtained in 204 patients--in 194 patients routinely (group 1) and in 10
      patients because of clinical indications (group 2). No obstructions or leaks were
      found in any of these 204 patients. In group 2, 304 patients were discharged
      without an UGI series and did well without any leak or obstruction, except for 1
      patient who returned 3 months postoperatively with a stricture at his
      jejunojejunostomy. No statistically significant differences were found between
      the 2 groups. CONCLUSION: The results of our study have shown that routine UGI
      studies after LRYGB do not contribute significantly to postoperative patient care
      at our institution. We now perform them selectively according to clinical
      indications, without this change adversely affecting our clinical outcomes.

PMID- 18065295
TI  - Preoperative weight loss is not a predictor of postoperative weight loss after
      laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: Identification of preoperative predictors of weight loss after
      laparoscopic Roux-en-Y gastric bypass (LRYGB) can lead to improved clinical
      outcomes. The purpose of this study was to determine whether preoperative weight
      loss was associated with improved percentage of excess weight loss (%EWL) 1 year
      after LRYGB. METHODS: A retrospective analysis was performed on the data from 295
      patients who had undergone LRYGB at our institution from July 2004 to November
      2005. Routine preoperative weight loss goals were implemented to facilitate the
      laparoscopic approach and ensure compliance with an appropriate nutritional and
      exercise program. Patients with an initial consultation BMI of <50, 50-59, and >
      or =60 kg/m(2) were given weight loss goals of 5 lb and 5% and 10% of body
      weight, respectively. RESULTS: The mean age was 45 +/- 10 years, and 89% were
      women and 70% were white. The mean BMI at the initial consultation was 51 +/- 7
      kg/m(2). A significant inverse correlation was found between the preoperative BMI
      and %EWL at 1 year postoperative (P <.001). When controlling for BMI, no
      correlation was found between the %EWL and percentage of preoperative weight loss
      or attainment of the weight loss goals. The weight loss goals were met or
      surpassed by 79% of patients, and the mean %EWL at 1 year was 66%. Whites had
      greater %EWL at 1 year postoperatively compared with African Americans (67%
      versus 61%; P = .002). When controlling for age, gender, race, and consultation
      BMI, the preoperative weight loss did not predict for the %EWL at 1 year.
      CONCLUSION: The results of this study have shown that preoperative weight loss
      does not predict postoperative weight loss 1 year after LRYGB. A lower BMI,
      younger age, and white race predicted better %EWL.

PMID- 18065296
TI  - Maintenance of weight loss in patients with body mass index >60 kg/m2: importance
      of length of small bowel bypassed.
AB  - BACKGROUND: It is commonly believed that weight loss after biliopancreatic
      diversion/duodenal switch is inversely related to the length of the alimentary
      limb and the common channel. However, the effect of the biliopancreatic limb
      length (BPL) on weight loss has received little attention. METHODS: A total of
      1001 patients after biliopancreatic diversion/duodenal switch (209 men and 792
      women, mean age 42 +/- 10 yr, mean body mass index [BMI] 52 +/- 9 kg/m(2)) were
      divided into 2 groups according to the ratio of the BPL to the total small bowel
      length (SBL): a BPL < or =45% of the SBL versus a BPL >45% of the SBL. The
      nutritional parameters and percentage of excess weight loss were compared between
      the 2 groups. RESULTS: In patients with a BMI of < or =60 kg/m(2), the percentage
      of excess weight loss at 1 year postoperatively was 66.8% for those with a BPL <
      or =45% of the SBL and 69.3% for those with a BPL >45% of the SBL (P = NS). At 2
      years, the corresponding percentages were 73.7% and 79.5% (P = NS) and, at 3
      years, were 73.4% and 75.2% (P = NS). In patients with a BMI >60 kg/m(2), the
      corresponding percentages of excess weight loss was 56.8% versus 61.4% (P = .07)
      at 1 year, 62.2% versus 77.5% (P = .04) at 2 years, and 59.8% versus 77.5% at 3
      years (P = .05). CONCLUSION: The results of our study have shown that amount of
      weight lost after biliopancreatic diversion/duodenal switch is directly related
      to the proportion of small bowel bypassed in patients with a BMI >60 kg/m(2).
      Also, the effect increased with the duration of follow-up. In less heavy
      patients, the BPL/SBL ratio had a minimal effect on long-term weight loss and a
      more pronounced effect on nutritional parameters.

PMID- 18065297
TI  - Angiosperm mitochondrial genomes and mutations.
AB  - Flowering plants harbor the largest mitochondrial genomes reported so far. At
      present, the nucleotide sequences of 15 mitochondrial genomes from seven
      angiosperm species are available, making detailed comparative analysis feasible.
      The gene content is variable among the species, but the most striking feature is
      the fluidity of intergenic regions, where species-specific sequences predominate.
      Additionally, angiosperm mitochondrial genomes, even within a species, show a
      remarkable amount of rearrangement. We also review mitochondrial mutants in
      angiosperms from a genomic viewpoint, and discuss how they have arisen. The
      involvement of nuclear genes in mitochondrial genome stability and organization
      is currently being revealed through the analysis of mutants.

PMID- 18065298
TI  - An HPLC-ICP-MS technique for determination of cadmium-phytochelatins in
      genetically modified Arabidopsis thaliana.
AB  - A reversed-phase high-performance liquid chromatographic technique was developed
      to separate cadmium-phytochelatin complexes (Cd-PC2, Cd-PC3, and Cd-PC4) of
      interest in the plant Arapidopsis thaliana. High-performance liquid
      chromatography (HPLC) was coupled to an inductively coupled plasma mass
      spectrometric (ICP-MS) system with some modification to the interface. This was
      done in order to sustain the plasma with optimum sensitivity for cadmium
      detection in the presence of the high methanol loads used in the gradient elution
      of the reversed-phase separation. The detection limits were found to be 91.8 ngl(
      1), 77.2 ngl(-1) and 49.2 ngl(-1) for Cd-PC2, Cd-PC3, and Cd-PC4 respectively.
      The regression coefficients (r2) for Cd-PC2 to Cd-PC4 detection ranged from 0.998
      to 0.999. The method was then used to investigate the occurrence and effect of
      cadmium-phytochelatin complexes in wild-type Arabidopsis and a phytochelatin
      deficient mutant cad1-3 that had been genetically modified to ectopically express
      the wheat TaPCS1 phytochelatin synthase enzyme. The primary complex found in both
      wild-type and transgenic plants was Cd-PC2. In both lines, higher levels of Cd
      PC2 were found in shoots than in roots, showing that phytochelatin synthases
      contribute to the accumulation of cadmium in shoots, in the Cd-PC2 form. Genetic
      modification did, however, impact the overall accumulation of Cd. Transgenic
      plants contained almost two times more cadmium in the form of Cd-PC2 in their
      roots than did the corresponding wild-type plants. Similarly, the shoot samples
      of the modified species also contained more (by 1.6 times) cadmium in the form of
      Cd-PC2 than the wild type. The enhanced role of PC2 in the transgenic Arabidopsis
      correlates with data showing long-distance transport of Cd in transgenic plants.
      Targeted transgenic expression of non-native phytochelatin synthases may
      contribute to improving the efficiency of plants for phytoremediation.

PMID- 18065299
TI  - Development and validation of a chemical hydrolysis method for dextromethorphan
      and dextrophan determination in urine samples: application to the assessment of
      CYP2D6 activity in fibromyalgia patients.
AB  - Dextromethorphan (DEM) is a widely used probe drug for human cytochrome P450 2D6
      isozyme activity assessment by measuring the ratio between DEM and its N
      demethylated metabolite dextrorphan (DOR). DOR is excreted in urine mainly
      conjugated to glucuronic acid. Prior to quantification, DOR must be deconjugated
      to avoid variability caused by the polymorphic glucuronosyltransferase enzyme. A
      chemical hydrolysis method was optimized using a chemometric approach. Three
      factors (acid concentration, hydrolysis time and temperature) were selected and
      simultaneously varied to study their effect on conjugated DOR hydrolysis.
      Hydrolysis conditions that maximize DOR release without significant degradation
      of both DEM and DOR were chosen and results were compared to those obtained by
      enzymatic method using beta-glucuronidase. An HPLC method with fluorescence
      detection was developed for the simultaneous quantitation of DEM, DOR and
      levallorphan, used as an internal standard. Separation was performed on a phenyl
      analytical column (150 mmx4.6 mm i.d., 5 microm) with a mobile phase consisting
      of 18% acetonitrile and 50 mM phosphoric acid (pH 3). The overall analytical
      procedure was validated and showed good performances in terms of selectivity,
      linearity, sensitivity, precision and accuracy. Finally, this assay was used to
      determine DEM/DOR molar ratios in fibromyalgia patients for the purpose of
      determining phenotype status for the CYP2D6.

PMID- 18065300
TI  - A novel method for preparing a protein-encapsulated bioaerogel: using a red
      fluorescent protein as a model.
AB  - A recombinant red fluorescent protein, DsRed, was chosen as a model protein to
      prepare a protein-encapsulated bioaerogel, DsRed-SAG. It was prepared using sol
      gel polymerization of tetraethyl orthosilicate (TEOS) with an ionic liquid as the
      solvent and pore-forming agent. The DsRed-SAG bioaerogel was characterized by
      Fourier transformation infrared, scanning electron microscopy and Brunauer-Emmett
      Teller measurements. It was found that the as-prepared bioaerogel had high
      porosity, and the silica network exhibited little shrinkage during the drying
      process. The stability of the bioaerogel was monitored by fluorescence
      spectroscopy and confirmed by confocal laser scanning microscopy. In addition,
      the protection of the encapsulated proteins by the silica network was further
      investigated using the degradation test by a protease. The results indicated that
      the as-prepared protein was quite stable during formation of the protein
      containing wet gel and extraction of the ionic liquid, demonstrating that the new
      method can be extended to prepare other protein-encapsulated bioaerogels.

PMID- 18065301
TI  - Dysplastic kidneys.
AB  - Dysplastic kidneys are common malformations affecting up to 1 in 1000 of the
      general population. They are part of the spectrum of Congenital Abnormalities of
      the Kidney and Urinary Tract (CAKUT) and an increasing number of children are
      being diagnosed on antenatal ultrasound. In the past, these patients may not have
      been detected until adulthood following investigation for other illness, or even
      as incidental findings at post mortem, unless there was severe bilateral
      dysplasia leading to Potter's sequence or renal failure in childhood. Excluding
      syndromic cases with defects in other organ systems, features linked to worse
      prognosis at presentation are: (1) bilateral disease; (2) decreased functional
      renal mass (which encompasses not just small kidneys but also large ones where
      cysts replace normal architecture); (3) lower urinary tract obstruction; and (4)
      anhydramnios or severe oligohydramnios. Dysplasia and renal function are dynamic
      and can evolve during pregnancy, so repeated assessment is necessary when
      pathology is expected. Worsening dimensions or decreasing amniotic fluid levels
      imply poorer prognosis, but there are no proven therapies during pregnancy,
      though vesicoamniotic shunting may be indicated with obstruction. Postnatal
      investigations aim to define the anatomy, which helps to estimate risks of
      infection and kidney function. Management might then involve observation,
      prophylactic antibiotics, surgery and/or renal support. Risks of renal malignancy
      and hypertension are low during childhood, but longer-term follow-up is needed,
      particularly to determine blood pressure and renal function in adulthood and
      pregnancy. Around 10% of cases have a family history of significant renal/urinary
      tract malformation. Monogenic causes include mutations in individual genes, such
      as TCF2/hepatocyte nuclear factor 1ss (HNF1beta), PAX2 and uroplakins, but there
      are also recent reports of children with compound heterozygote mutations in
      several renal/urinary tract developmental genes. Effective genetic screening in
      future may require gene chip or other techniques to assess multiple genes
      concurrently, but this should not replace a multidisciplinary approach to these
      often difficult cases.

PMID- 18065303
TI  - The evolving means of protecting horses against West Nile infection through
      immunisation.

PMID- 18065304
TI  - Safety of an attenuated West Nile virus vaccine, live Flavivirus chimera in
      horses.
AB  - REASON FOR PERFORMING STUDY: West Nile virus (WNV) infection is endemic and able
      to cause disease in naive hosts. It is necessary therefore to evaluate the safety
      of new vaccines. OBJECTIVES: To establish: 1) the safety of a modified live
      Flavivirus/West Nile virus (WN-FV) chimera by administration of an overdose and
      testing for shed of vaccine virus and spread to uninoculated sentinel horses; 2)
      that this vaccine did not become pathogenic once passaged in horses; and 3)
      vaccine safety under field conditions. METHODS: There were 3 protocols: 1) In the
      overdose/shed and spread study, horses were vaccinated with a 100x immunogenicity
      overdose of WN-FV chimera vaccine and housed with sentinel horses. 2) A reversion
      to virulence study, where horses were vaccinated with a 20x immunogenicity
      overdose of WN-FV chimera vaccine. Horses in both studies were evaluated for
      abnormal health conditions and samples obtained to detect virus, seroconversion
      and dissemination into tissues. 3) In a field safety test 919 healthy horses of
      various ages, breeds and sex were used. RESULTS: Vaccination did not result in
      site or systemic reactions in either experimental or field-injected horses. There
      was no shed of vaccine virus, no detection of vaccine virus into tissue and no
      reversion to virulence with passage. CONCLUSIONS: WN-FV chimera vaccine is safe
      to use in horses with no evidence of ill effects from very high doses of vaccine.
      There was no evidence of reversion to virulence. In addition, administration of
      this vaccine to several hundred horses that may have been previously exposed to
      WNV or WNV vaccine resulted in no untoward reactions. POTENTIAL RELEVANCE: These
      studies establish that this live attenuated Flavivirus chimera is safe to use for
      immunoprophylaxis against WNV disease in horses.

PMID- 18065305
TI  - Efficacy, duration, and onset of immunogenicity of a West Nile virus vaccine,
      live Flavivirus chimera, in horses with a clinical disease challenge model.
AB  - REASON FOR PERFORMING STUDY: West Nile virus (WNF) is a Flavivirus responsible
      for a life-threatening neurological disease in man and horses. Development of
      improved vaccines against Flavivirus infections is therefore important.
      OBJECTIVES: To establish that a single immunogenicity dose of live Flavivirus
      chimera (WN-FV) vaccine protects horses from the disease and it induces a
      protective immune response, and to determine the duration of the protective
      immunity. METHODS: Clinical signs were compared between vaccinated (VACC) and
      control (CTRL) horses after an intrathecal WNV challenge given at 10 or 28 days,
      or 12 months post vaccination. RESULTS: Challenge of horses in the immunogenicity
      study at Day 28 post vaccination resulted in severe clinical signs of WNV
      infection in 10/10 control (CTRL) compared to 1/20 vaccinated (VACC) horses
      (P<0.01). None of the VACC horses developed viraemia and minimal histopathology
      was noted. Duration of immunity (DPI) was established at 12 months post
      vaccination. Eight of 10 CTRL exhibited severe clinical signs of infection
      compared to 1 of 9 VACC horses (P<0.05). There was a significant reduction in the
      occurrence of viraemia and histopathology lesion in VACC horses relative to CTRL
      horses. Horses challenged at Day 10 post vaccination experienced moderate or
      severe clinical signs of WNV infection in 3/3 CTRL compared to 5/6 VACC horses
      (P<0.05). CONCLUSIONS: This novel WN-FV chimera vaccine generates a protective
      immune response to WNV infection in horses that is demonstrated 10 days after a
      single vaccination and lasts for up to one year. POTENTIAL RELEVANCE: This is the
      first USDA licensed equine WNV vaccine to utilise a severe challenge model that
      produces the same WNV disease observed under field conditions to obtain a label
      claim for prevention of viraemia and aid in the prevention of WNV disease and
      encephalitis with a duration of immunity of 12 months.

PMID- 18065306
TI  - A case-control study of factors associated with development of clinical disease
      due to West Nile virus, Saskatchewan 2003.
AB  - REASON FOR PERFORMING STUDY: West Nile virus (WNV) was first diagnosed in
      Saskatchewan equids in 2002. AWNV epidemic was considered highly likely for 2003,
      which would provide a unique opportunity to study all aspects of WNV subclinical
      infection and clinical disease development in a relatively naive population.
      HYPOTHESIS: There are individual equid attributes and management risk factors
      associated with development of clinical disease. Specifically, this study could
      address the question of vaccine efficacy for the prevention of development of
      clinical disease. METHODS: A case-control study was conducted in the summer of
      2003 during a province-wide outbreak of WNV. Between 5 and 10 equids were sampled
      from each of 23 case premises with clinical disease and 23 control premises with
      no apparent or confirmed clinical disease. Data were analysed to identify risk
      factors for the development of clinical disease. RESULTS: The proportion of
      equids serologically positive for natural exposure to West Nile virus was 64%
      (193/300). Nonvaccinated equids were 23 times (95%CI limits 3.0, 168.5, P =
      0.002) more likely to develop clinical disease than those vaccinated. The
      estimate of vaccine efficacy in this field study was 96% (95%CI limits 67%, 99%).
      CONCLUSIONS: The study demonstrated that vaccination was strongly associated with
      the prevention of clinical disease. POTENTIAL RELEVANCE: Vaccination is an
      effective, practical method of prevention of clinical disease.

PMID- 18065307
TI  - Influence of breed and oestrous cycle on endometrial gland surface density in the
      mare.
AB  - REASON FOR PERFORMING STUDY: The diffuse noninvasive epitheliochorial equine
      placenta develops an intimate and complex interdigitation with the maternal
      endometrium throughout gestation to maximise surface contact and, consequently,
      optimise nutritional and gaseous maternofetal exchanges. A significant reduction
      occurs in the surface density of microcotyledons on the placentae of Welsh Pony
      vs. Thoroughbred mares that may relate to a difference in either the number or
      density of endometrial glands between these breeds. OBJECTIVES: To examine this
      hypothesis and to determine the influence of the oestrous cycle upon the
      development and surface density of endometrial glands. METHODS: Endometrial
      biopsies were taken under videoendoscopic visual control from the base of a
      uterine horn from young, fertile, Welsh Pony and Thoroughbred mares at defined
      stages of the oestrous cycle. Computer-assisted morphometric analysis then
      permitted the surface density of endometrial glands within the stratum spongiosum
      to be assessed. CONCLUSIONS: There was a statistically significant reduction in
      endometrial gland surface density in the Welsh Pony vs. Thoroughbred mares during
      both oestrus and dioestrus. POTENTIAL RELEVANCE: A substantial upregulation of
      epidermal growth factor (EGF) mRNA in the epithelial cells lining the apical
      portions of endometrial glands has been demonstrated in pregnant mares between
      Days 35 and 40 after ovulation, coincident with the onset of interdigitation
      between the allantochorion and endometrium to form the microcotyledonary
      placenta. The increased surface density of endometrial glands noted in the uteri
      of Thoroughbred mares might account for the greater surface density of placental
      microcotyledons in this breed.

PMID- 18065308
TI  - Endometrial gland surface density and hyperaemia of the endometrium during early
      pregnancy in the mare.
AB  - REASON FOR PERFORMING STUDY: The morphology and surface density of endometrial
      glands responsible for the nutrition of the placenta requires further study
      employing computer assisted morphometric analysis. OBJECTIVES: To analyse changes
      in the morphology and surface density of endometrial glands situated adjacent to,
      and remote from, the conceptus during the first 30 days of gestation. METHODS:
      Endometrial biopsies were recovered, under videoendoscopic control, from both
      nonpregnant and pregnant mares 12 days after ovulation, as well as from pregnant
      mares on Days 16, 20, 25 and 30 of gestation. One biopsy was taken at the base of
      the nongravid uterine horn and the other from beneath the conceptus at the base
      of the gravid horn. The samples were evaluated by computer assisted morphometric
      analysis to determine the surface area per unit volume (Sv) of endometrial glands
      in the stratum spongiosum. RESULTS: No differences in morphology or density of
      the glands were discernable between pregnant and nonpregnant mares on Day 12 day
      after ovulation. On Day 16, however, the glands beneath the conceptus appeared to
      be at a significantly lower density than the clearly more tortuous glands at the
      base of the nongravid horn. Between Days 20 and 30 of gestation the endometrium
      in direct contact with the conceptus was visibly more reddened and hyperaemic
      than elsewhere in the uterus. However, the Sv of glands beneath the conceptus had
      now increased again so they appeared similar to those in the nongravid horn, due
      mainly to a reduction in the level of stromal oedema in the former. CONCLUSIONS
      AND POTENTIAL RELEVANCE: The embryo-maternal interactions that are vital during
      early pregnancy to suppress the cyclical luteolytic cascade and support nidation
      of the conceptus, were characterised here with local endometrial hyperaemia,
      histotroph production and a decrease in endometrial gland Sv at the commencement
      of the stationary phase. Both the components secreted by the endometrial glands
      and the factors liberated by the conceptus during early pregnancy need further
      investigation.

PMID- 18065309
TI  - Alternative vaccination against equine botulism (BoNT/C).
AB  - REASON FOR PERFORMING STUDY: In Europe the incidence of botulism in horses has
      increased in the last decade due to the growing popularity of haylage feeding.
      Recombinant vaccines are safer and less expensive to produce and are generally
      better tolerated than toxoids. OBJECTIVES: To investigate whether the recombinant
      C-terminal half of the heavy chain of the botulinum neurotoxin C (Hc BoNT/C) in
      combination with an immunstimulatory adjuvant is an appropriate vaccine candidate
      for horses by testing its efficacy to induce neutralising antibodies and by
      comparing its immunogenic properties and adverse reactions to a commercial toxoid
      vaccine. Formation of oedema and local pain reactions were assessed. ELISA and
      Western blot assay against Hc BoNT/C and testing of neutralising antibody
      induction in a mouse protection assay were used to evaluate the immune response.
      RESULTS: With the recombinant vaccine, only minor local swelling with full
      recovery after 5 days was noted after brisket injections. The toxoid vaccine
      produced local, painful reactions with longer recovery periods of up to 2 weeks.
      Horses vaccinated with either vaccine induced neutralising antibodies after the
      second booster vaccination, while seroconversion on ELISA and Western blot to Hc
      BoNT/C was apparent after the first recombinant vaccination, and at various time
      points in the vaccination schedule in horses that received commercial toxoid
      vaccine. CONCLUSION: The recombinant vaccine showed fewer adverse reactions
      compared to the only commercially available vaccine but induced similar
      concentrations of neutralising antibodies. There was no correlation between the
      serological response to Hc BoNT/C and the neutralising capacity of serum.
      POTENTIAL RELEVANCE: Recombinant Hc BoNT/C is an appropriate vaccine candidate to
      stimulate production of neutralising antibodies against botulinum neurotoxin C in
      horses and creates only minor local reactions at the injection site.

PMID- 18065310
TI  - Clinical, immunophenotypic and functional characterisation of T-cell leukaemia in
      six horses.
AB  - REASON FOR PERFORMING STUDY: Lymphoid leukaemia (LL) is rare in equids. In man,
      immunophenotypic classification identifies distinct leukaemic types with
      different treatment strategies. Improved understanding and classification of
      equine LL may allow similar advances. OBJECTIVES: To document the clinical,
      immunophenotypic and functional characteristics in 6 cases of equine LL of T-cell
      origin. METHODS: The clinical records and pathological findings from 6 cases of
      equine LL were analysed. Immunohistochemistry to identify T or B lymphocytes was
      performed on paraffin embedded tissues in 4 cases. Peripheral blood mononuclear
      cells (PBMC) were phenotyped for expression of CD4, CD8, MHC class I and II and B
      cell antigens in 4 cases using monoclonal antibodies (mAbs) and flow cytometry.
      Neoplastic lymphocytes from 4 horses were stimulated with mitogens. RESULTS AND
      CONCLUSIONS: Six horses of various breeds were identified with LL of T-cell
      origin. The clinical course and presenting signs varied. Neoplastic lymphocytes
      were identified in peripheral blood samples from all horses and tissue invasion
      was confirmed at examination post mortem in 4 horses. Immunophenotyping
      identified a predominance of CD3+ T-cells in lymphoid tissues and CD4+ T-cells in
      circulating peripheral blood mononuclear cells (PBMC) in the affected horses.
      Neoplastic lymphocytes from the 4 cases that were tested failed to proliferate in
      response to mitogens. POTENTIAL RELEVANCE: Characterisation of the clinical,
      pathological and immunological findings in 6 horses with LL has added to reports
      of this rare condition, characterised it in greater detail and therefore provides
      a starting point for further investigations.

PMID- 18065311
TI  - Interpretation of serum antibody response to Anoplocephala perfoliata in relation
      to parasite burden and faecal egg count.
AB  - REASON FOR PERFORMING STUDY: Increased knowledge is needed to assist in the
      interpretation of presently available diagnostic techniques for infection by the
      tapeworm Anoplocephala perfoliata in horses. HYPOTHESIS: The suggested cut-off
      level of an A. perfoliata specific ELISA may not adequately reflect the actual
      infection level. Hence, faecal egg counts may be a more useful diagnostic test
      for individual horses than previously reported. METHODS: Eighty-four horses
      admitted for slaughter at a Danish abattoir were examined for the presence of A.
      perfoliata. The number of tapeworms, their stage of development and gross
      pathological mucosal lesions were recorded and compared with serum antibody
      responses and faecal egg counts. Faecal egg counts were determined in samples
      from A. perfoliata infected horses using a semi quantitative
      centrifugation/flotation technique. Blood samples collected at slaughter were
      analysed by ELISA to determine serum antibody levels against A. perfoliata 12/13
      kDa excretory/secretory antigens. RESULTS: Macroscopically visible tapeworms were
      detected in 24 (29%) of the horses. The overall sensitivity of the faecal egg
      count was found to be 0.46; however, if the detection limit was increased to
      above 20 tapeworms, sensitivity increased to 0.89. There was a correlation of
      0.71 between worm burden and egg count. The antibody levels correlated
      significantly with infection intensity despite a wide variation among horses with
      similar levels of infection. The optimal cut-off value was determined using
      receiver operating characteristic analysis. If cut-off was chosen at optical
      density (OD) = 0.7, sensitivity was 0.68 and specificity 0.71. CONCLUSIONS: Both
      diagnostic methods were capable of revealing potentially pathogenic infections,
      with the faecal egg count being more applicable on the individual horse level.
      POTENTIAL RELEVANCE: In the population of Danish horses investigated the serum
      ELISA test should be interpreted such that horses in need of anti-Anoplocephala
      treatment have an OD = 0.7 or above.

PMID- 18065312
TI  - Effects of analgesia of the digital flexor tendon sheath on pain originating in
      the sole, distal interphalangeal joint or navicular bursa of horses.
AB  - REASON FOR PERFORMING STUDY: Specific analgesic techniques are required in
      diagnosis of lameness to isolate the exact origin of pain to the many structures
      of the foot that may be involved. OBJECTIVE: To determine if analgesia of the
      digital flexor tendon sheath (DFTS) results in anaesthesia of other portions of
      the foot, such as the sole, distal interphalangeal joint (DIPJ), or navicular
      bursa (NB). METHODS: Lameness caused by pain in the dorsal margin or heel region
      of the sole of the foot was induced in 18 horses by: using set-screws to create
      solar pressure (Trial 1: n = 5); or administering endotoxin intrasynovially into
      the DIPJ (Trial 2: n = 6) and NB (Trial 3: n = 7). The gait of each horse was
      evaluated by examining videotape recorded before and after creation of lameness
      and after administration of mepivacaine hydrochloride into the DFTS. RESULTS:
      Median lameness scores in Trial 1 at 10 min post injection of the DFTS were not
      significantly different from those before administration of local anaesthetic
      solution into the DFTS (P> or =0.05), but median lameness scores were reduced
      significantly at 20 min (P< or =0.05). In Trials 2 and 3, median lameness scores
      were not significantly different at observations made at 10 and 20 min post
      injection of the DFTS. CONCLUSIONS: Analgesia of the DFTS has little effect on
      lameness caused by pain originating in the sole, DIPJ or NB. POTENTIAL RELEVANCE:
      Improvement of lameness in horses after intrasynovial analgesia of the DFTS is
      probably caused by attenuation of pain within the structures contained in the
      DFTS.

PMID- 18065313
TI  - Superficial digital flexor tendon lesions in racehorses as a sequela to muscle
      fatigue: a preliminary study.
AB  - REASON FOR PERFORMING STUDY: Racing and training related lesions of the forelimb
      superficial digital flexor tendon are a common career ending injury to racehorses
      but aetiology and/or predisposing causes of the injury are not completely
      understood. OBJECTIVES: Although the injury takes place within the tendon, the
      lesion must be considered within the context of the function of the complete
      suspensory system of the distal limb, including the associated muscles. METHODS:
      Both muscle and tendon function were investigated in vivo using implanted strain
      gauges in 3 Thoroughbred horses walking, trotting and cantering on a motorised
      treadmill. These data were combined with assessments of muscle architecture and
      fibre composition to arrive at an overview of the contribution of each muscle
      tendon unit during locomotion. RESULTS: The superficial digital flexor muscle has
      fatigue-resistant and high force production properties that allow its tendon to
      store and return elastic energy, predominantly at the trot. As running speed
      increases, deep digital flexor tendon force increases and it stabilises
      hyperextension of the fetlock, thus reinforcing the superficial digital flexor in
      limb load support. The deep digital flexor muscle has fast contracting properties
      that render it susceptible to fatigue. CONCLUSION: Based on these measurements
      and supporting evidence from the literature, it is proposed that overloading of
      the superficial digital flexor tendon results from fatigue of the synergistic,
      faster contracting deep digital flexor muscle. POTENTIAL RELEVANCE: Future
      research investigating distal limb system function as a whole should help refine
      clinical diagnostic procedures and exercise training approaches that will lead to
      more effective prevention and treatment of digital flexor tendon injuries in
      equine athletes.

PMID- 18065314
TI  - Hypertrophy and physiological death of equine chondrocytes in vitro.
AB  - REASON FOR PERFORMING STUDY: Equine osteochondrosis results from a failure of
      endochondral ossification during skeletal growth. Endochondral ossification
      involves chondrocyte proliferation, hypertrophy and death. Until recently no
      culture system was available to study these processes in equine chondrocytes.
      OBJECTIVE: To optimise an in vitro model in which equine chondrocytes can be
      induced to undergo hypertrophy and physiological death as seen in vivo. METHODS:
      Chondrocytes isolated from fetal or older (neonatal, growing and mature) horses
      were cultured as pellets in 10% fetal calf serum (FCS) or 10% horse serum (HS).
      The pellets were examined by light and electron microscopy. Total RNA was
      extracted from the pellets, and quantitative PCR carried out to investigate
      changes in expression of a number of genes regulating endochondral ossification.
      RESULTS: Chondrocytes from fetal foals, grown as pellets, underwent hypertrophy
      and died by a process morphologically similar to that seen in vivo. Chondrocytes
      from horses age >5 months did not undergo hypertrophy in pellet culture. They
      formed intramembranous inclusion bodies and the cultures included cells of
      osteoblastic appearance. Pellets from neonatal foals cultured in FCS resembled
      pellets from older horses, however pellets grown in HS underwent hypertrophy but
      contained inclusion bodies. Chondrocytes from fetal foals formed a typical
      cartilage-like tissue grossly and histologically, and expressed the cartilage
      markers collagen type II and aggrecan mRNA. Expression of Sox9, collagen type II,
      Runx2, matrix metalloproteinase-13 and connective tissue growth factor mRNA
      increased at different times in culture. Expression of fibroblast growth factor
      receptor-3 and vascular endothelial growth factor mRNA decreased with time in
      culture. CONCLUSIONS: Freshly isolated cells from fetal growth cartilage cultured
      as pellets provide optimal conditions for studying hypertrophy and death of
      equine chondrocytes. POTENTIAL RELEVANCE: This culture system should greatly
      assist laboratory studies aimed at elucidating the pathogenesis of
      osteochondrosis.

PMID- 18065315
TI  - Sedation with detomidine and acepromazine influences the endoscopic evaluation of
      laryngeal function in horses.
AB  - REASON FOR PERFORMING STUDY: Endoscopy of the upper airways of horses is used as
      a diagnostic tool and at purchase examinations. On some occasions it is necessary
      to use sedation during the procedure and it is often speculated that the result
      of the examination might be influenced due to the muscle-relaxing properties of
      the most commonly used sedatives. OBJECTIVES: To evaluate the effect of
      detomidine (0.01 mg/kg bwt) and acepromazine (0.05 mg/kg bwt) on the appearance
      of symmetry of rima glottidis, ability to abduct maximally the arytenoid
      cartilages and the effect on recurrent laryngeal neuropathy (RLN) grade. METHODS:
      Forty-two apparently normal horses underwent endoscopic examination of the upper
      airways on 3 different occasions, under the influence of 3 different treatments:
      no sedation (control), sedation with detomidine and sedation with acepromazine.
      All examinations were performed with a minimum of one week apart. The study was
      performed as an observer-blind cross-over study. RESULTS: Sedation with
      detomidine had a significant effect on the RLN grading (OR = 2.91) and ability
      maximally to abduct the left arytenoid cartilages (OR = 2.91). Sedation with
      acepromazine resulted in OR = 2.43 for the RLN grading and OR = 2.22 for the
      ability to abduct maximally. The ability to abduct maximally the right arytenoid
      cartilage was not altered. CONCLUSIONS: Sedating apparently healthy horses with
      detomidine or acepromazine significantly impairs these horses' ability to abduct
      fully the left but not the right arytenoid cartilage. This resulted in different
      diagnosis with respect to RLN when comparing sedation to no sedation. POTENTIAL
      RELEVANCE: Since the ability to abduct the right arytenoid cartilage fully is not
      altered by sedation, it is speculated that horses changing from normal to
      abnormal laryngeal function when sedated, might be horses in an early stage of
      the disease. To confirm or reject these speculations, further studies are needed.
      Until then sedation during endoscopy should be used with care.

PMID- 18065316
TI  - Platelet activation in ponies with airway inflammation.
AB  - REASON FOR PERFORMING STUDY: Platelet activation occurs in human obstructive
      airway diseases and in laboratory animal models. However, there is limited
      evidence that platelets may be involved in equine recurrent airway obstruction
      (RAO) and other inflammatory diseases. This study investigated whether platelet
      activation also occurred in RAO. HYPOTHESIS: Platelet function is altered in
      ponies with active RAO. This alteration can be detected ex vivo by measuring
      platelet adhesion. METHODS: An in vitro platelet adhesion assay measuring acid
      phosphatase (AcP) activity colorimetrically was adapted for use with equine
      platelets and responses to selected agonists were established. Platelet adhesion
      and aggregation was evaluated in vitro on platelets isolated from 6 ponies with
      RAO before, during and after a 7 h natural antigen challenge. Three ponies with
      no history of airway disease were also studied. RESULTS: Adhesion of equine
      platelets to serum coated plastic was detected at concentrations of 10-100
      radicalo 10(9)/l. Adhesion increased in response to stimulation with platelet
      activating factor and thrombin, but not equine interleukin 8. Prior to the
      antigen challenge, adhesion of nonstimulated platelets was low and increased
      significantly (P<0.05) 24 h after initiation of the challenge in RAOs, but not in
      the normal animals. No changes in platelet aggregation were noted in either
      group. CONCLUSIONS: The described assay offers an alternative method to evaluate
      platelet function in healthy and diseased horses and can detect changes not
      observed using a classic aggregation assay. Circulating platelets are activated
      24 h after antigen challenge of ponies with RAO and may play a role in pulmonary
      inflammation and/or the pathophysiology of RAO. POTENTIAL RELEVANCE:
      Investigating platelet function in RAO and airway inflammation may reveal new
      aspects of the pathogenesis of inflammatory lung disease in the horse.

PMID- 18065317
TI  - Severe collapse of the rostral soft palate as a source of abnormal respiratory
      noise in six ponies and horses.

PMID- 18065318
TI  - Factors affecting clinical assessment of insulin sensitivity in horses.
AB  - Insulin resistance is thought to be involved in the pathogenesis of many equine
      conditions such as pars intermedia dysfunction, equine metabolic syndrome,
      diabetes mellitus, hyperlipaemia, laminitis, endotoxaemia and osteochondrosis
      dissecans (OCD); whereas polysaccharide storage myopathy in Quarter Horses and
      equine motor neuron disease (EMD) have been associated with increased insulin
      sensitivity. However, it is clear that there is not one ideal test, in terms of
      both practicality and accuracy, for evaluating insulin sensitivity in horses and
      improved diagnostic techniques are required. This review sets out the background
      to the subject and identifies current knowledge regarding the measurement of
      insulin sensitivity by tolerance testing and clamping techniques. Factors
      affecting insulin sensitivity, such as breed, pregnancy, lactation, obesity and
      nutritional factors are discussed. In addition, the relationship with training,
      nutritional supplementation and drug administration are considered.

PMID- 18065319
TI  - A severe coarctation of the aorta incidentally diagnosed during cardiac
      catheterization of a 40-year-old male patient presenting acute coronary syndrome.

PMID- 18065320
TI  - An unusual severe pulmonic stenosis case without significant electrocardiographic
      changes.

PMID- 18065321
TI  - Calcified giant congenital non-coronary sinus Valsalva aneurysm ruptured into the
      left ventricular outflow tract.

PMID- 18065322
TI  - Aortopulmonary window associated with anomalous right coronary artery: a rare
      combination.

PMID- 18065323
TI  - Coronary to pulmonary artery fistula associated with significant coronary
      atherosclerosis.

PMID- 18065324
TI  - Transcatheter closure of large fistula between right coronary artery and
      pulmonary artery using Amplatzer vascular plug in a patient with pulmonary
      atresia and ventricular septal defect.

PMID- 18065325
TI  - [Retrograde blood flow from saphenous venous graft to the aorta].

PMID- 18065326
TI  - [Paradoxical embolism after thrombolytic treatment in a patient with pulmonary
      embolism and right atrial thrombus].

PMID- 18065327
TI  - An uncommon coincidence of congenital quadricuspid aortic valve accompanied by
      hypertrophic obstructive cardiomyopathy.

PMID- 18065328
TI  - An anomalous left coronary artery detected by multislice computed tomography.

PMID- 18065329
TI  - [What is done, what will be done?].

PMID- 18065330
TI  - Prevention of calcification with TPEN in pericardial bioprosthetic heart valve
      material.
AB  - OBJECTIVE: Calcification is a frequent cause of the clinical failure of
      bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine
      pericardium. The major object of the present study is to prevent calcification of
      pericardial bioprosthetic heart valve materials with TPEN. METHODS: Bovine
      pericardium was cut into 2-cm 2 pieces, rinsed in phosphate-buffered saline
      solution, transferred into +4 degrees C phosphate-buffered saline containing
      0.625% glutaraldehyde for initial fixation for 48 h, and allocated into two
      groups. Control samples were treated in an identical fresh solution for five more
      days. Others underwent additional fixation in phosphate-buffered saline 2microM
      TPEN for 48 h. They were then transferred into phosphate-buffered saline + 0.625%
      glutaraldehyde solution at 37 degrees C (pH 7.4) for three more days. Pericardial
      patches were inserted into the dorsal pouches of 18 juvenile male Wistar rats as
      control and study groups. Rats were divided into two groups and sacrificed
      consecutively by the end of 9th and 12th weeks. The biomechanical properties and
      calcium contents of explanted tissues were tested and were also assessed
      histopathologically. RESULTS: The difference in the calcium contents of the
      control and study groups' pericardial tissues at the 9th, and 12th weeks were
      statistically significant (p=0.0001, p=0.0001). The comparison of calcium
      contents between controls of 9th and 12th weeks and study groups' of the 9th and
      12th weeks pericardial tissues were also significant (p=0.0001 and p=0.0001).
      Histopathologic and biomechanical assessment also supported these findings.
      CONCLUSION: Calcific degeneration of glutaraldehyde-fixed bovine pericardium can
      be reduced by using TPEN without any effect on durability.

PMID- 18065331
TI  - Cardiovascular risk factors in obese women and their first-degree relatives.
AB  - OBJECTIVE: Evidence for a connection between obesity and cardiovascular disease
      is derived from epidemiological studies. The aim of this study was to evaluate
      the cardiovascular risk factors in obese women and their first-degree relatives.
      METHODS: Fifty-five obese women and their 154 first-degree relatives (daughter,
      son, sister, brother), 60 non-obese women and their 100 first-degree relatives
      were enrolled in this cross-sectional controlled study. Blood pressure, heart
      rate, body mass index (BMI), waist-to-hip ratio (WHpR), waist circumference (WC)
      and lipid levels were measured in all participants. Serum concentrations of
      insulin were measured by chemiluminescence method, plasma levels of high
      sensitive C-reactive protein (hs CRP) by immunoturbimetric assay and fibrinogen
      by coagulation method. Measurement of insulin resistance (IR) was calculated
      using homeostasis model assessment (HOMA). Statistical analysis was preformed
      using Chi-square, Student's t and Mann-Whitney U tests. The relationship between
      obesity indices and cardiovascular risk factors were studied using linear
      regression analysis. RESULTS: Mean values of BMI in female and male relatives
      were found as 25.10+/-2.5 kg/m2 and 23.5+/-4.98 kg/m2, respectively. In
      relatives, the frequencies of obesity, overweight and normal weight were found to
      be 8.9%, 25.8% and 65.1%, respectively. Central obesity was found higher in males
      than in females in the first-degree relatives, using WC (28.5% vs. 14.3%,
      p=0.001) or WHpR (30.9% vs. 24.5%, p=0.002). Elevated blood pressure (>or=140/90
      mmHg) was recorded in 23.6% of obese women and in 8.4% of their relatives. Mean
      HOMA-IR levels of obese women and their relatives were found as 3.26+/-0.7 and
      2.07+/-1.1, respectively. Mean hs CRP levels of obese women and their relatives
      were 0.98+/-0.08 mg/dl and 0.23+/-0.03 mg/dl, respectively (p=0.002). Mean
      fibrinogen levels of obese women and their relatives were 443.21+/-45.9 mg/dl and
      321.10+/-38.23 mg/dl, respectively. CONCLUSION: In obese women and their
      relatives, body mass index and waist circumferences are related with blood
      pressure, total cholesterol, fibrinogen and insulin resistance. If there are
      obese women in family, first-degree relatives have 1.8 fold increased obesity
      frequency. Body mass index increases together with cardiovascular risk factors.
      In early term, prevention of obesity may decrease developing of cardiovascular
      risk.

PMID- 18065332
TI  - [Relationship between the severity of obstructive sleep apnea and hypertension].
AB  - OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is a syndrome defined
      frequently by decrease in arterial oxygen saturation and repeated upper airway
      obstruction episodes during sleep. The most important complications of OSAS
      patients belong to cardiovascular system. Systemic arterial hypertension (43
      60%), pulmonary hypertension (20-30%), coronary artery disease (20-30%) and
      congestive heart failure (5-10%) are among OSAS associated cardiovascular disease
      spectrum. In this study, we investigated the frequency of hypertension (HT),
      which is the most common cardiovascular disease seen in patients admitted with
      OSAS suspicion. METHODS: Overall 263 consecutive patients with possible OSAS were
      included in this cross-sectional study. Diagnostic polysomnography (PSG) was
      performed in all patients with 44-channel polysomnograph (Compumedics E series,
      Australia) one whole night. Sleep stages and respiratory events were manually
      scored. Patients with apnea hypopnea index (AHI) <5 were diagnosed as OSAS
      negative, patients with AHI between 5-14 were diagnosed as mild OSAS, patients
      with AHI between 15-29 were diagnosed as moderate OSAS, patients with AHI >or=30
      were diagnosed as severe OSAS. Relation of OSAS and presence of HT was
      statistically analyzed with Chi-square test. RESULTS: According to PSG records of
      the patients who were assessed with OSAS suspicion, 54 (20.5%) patients were
      assessed as OSAS negative, 26(9.9%) - mild OSAS, 45 (17.1%) - moderate OSAS, and
      138 (52.5%) were diagnosed as severe OSAS. Hypertension was present in 4 (7.4%)
      of 54 OSAS negative patients and 56 (36.8%) of 209 patients with OSAS, the
      difference was significant (p=0.001). When we assessed mild OSAS patients and
      moderate-severe OSAS patients in terms of HT frequency, HT was present in a lower
      rate in mild OSAS patients as compared with patients with moderate-severe OSAS
      (3/26 versus 53/183; p=0.044). When we compared OSAS negative patients with
      moderate-severe OSAS patients, HT was less frequently found in OSAS negative
      patients (4/54 versus 53/183, p=0.001). CONCLUSION: It is determined that
      hypertension was more frequently seen in patients with OSAS than in patients
      without OSAS and that HT frequency increased in parallel to the severity of OSAS.

PMID- 18065333
TI  - Effect of nebivolol and metoprolol treatments on serum asymmetric
      dimethylarginine levels in hypertensive patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: Elevated asymmetric dimethylarginine (ADMA) levels, an endogenous
      inhibitor of nitric oxide synthase, are an important cardiovascular risk factor.
      In patients with diabetes, increased ADMA levels have been reported, which may be
      associated with endothelial dysfunction. In this study, effect of nebivolol on
      serum ADMA levels in hypertensive patients with type 2 diabetes have been
      compared with metoprolol, an another beta-blocker. METHODS: A total of 54
      patients (27 female, 27 male; mean age: 53.0+/-8.7 years) with type 2 diabetes
      and hypertension were included in this randomized, open-label, prospective study.
      Patients were randomized to receive either nebivolol 5 mg/day (n=28) or
      metoprolol 100 mg/day (n=26) for 12 weeks. When the patients could not reach
      target blood pressure levels at the end of week 4, indapamide (2.5 mg/day) was
      added. Enzyme Linked Immunosorbent Assay was used for serum ADMA measurements.
      RESULTS: Similar reductions in blood pressure values were observed in both groups
      (p>0.05). In nebivolol group, there were no significant changes in serum ADMA
      levels compared to baseline (0.6+/-0.2 micromol/l vs 0.6+/-0.1 micromol/l,
      p>0.05), whereas in metoprolol group a 35.6% increase in serum ADMA levels was
      observed (0.6+/-0.1 micromol/l vs 0.7+/-0.2 micromol/l, p<0.01). CONCLUSION: We
      observed a significant increase in ADMA levels, a marker of endothelial
      dysfunction, during metoprolol treatment, whereas nebivolol had neutral effects
      on ADMA levels in patients with type 2 diabetes mellitus and hypertension.

PMID- 18065334
TI  - Does nebivolol improve endothelial dysfunction and will it rescue the reputation
      of the beta-blockers in the future?

PMID- 18065335
TI  - Minimizing short-term complications in patients who have undergone cardiac
      invasive procedure: a randomized controlled trial involving position change and
      sandbag.
AB  - OBJECTIVE: The study aimed to evaluate the effects of putting a sandbag on
      femoral access site after cardiac invasive procedure and changing patients'
      position in bed on vascular complications rate and the severity of back pain
      related to the duration of bed rest after procedure. METHODS: This randomized
      controlled study included 169 patients divided into five different groups
      assigned randomly. Group 1 patients were applied 4.5 kg sandbag for 30 minutes
      and Group 2 patients were applied 2.3 kg sandbag for 2 hours on femoral access
      site after procedure. Group 1 and 2 patients' body positions were changed every
      hour beginning from the second hour. Group 3 patients received application of 4.5
      kg sandbag for 30 minutes and Group 4 patients were applied 2.3 kg sandbag for 2
      hours on femoral access site after procedure and these patients' body positions
      were not changed after catheterization. Group 5 patients remained in supine
      position without changing position and had no application of a sandbag. RESULTS:
      The incidence of vascular complications was not significantly different in the
      group with application of sandbag when compared with the group without
      application of sandbag. Back pain was reported more often in the patients whose
      positions were not changed and whose heads of beds were not raised (p<0.05).
      CONCLUSION: Sandbag was not effective in decreasing the incidence of the vascular
      complications after procedure. To increase the comfort and to decrease the back
      pain of the patient, the patient's position should be changed and the head of the
      bed should be raised about 30 or 45 degrees.

PMID- 18065336
TI  - Evaluation of hemodynamic changes in patients with mitral valve replacement using
      dobutamine stress echocardiography.
AB  - OBJECTIVE: The aim of this study was to investigate the response of heart to
      stress according to the size of the prosthetic valve in patients who had
      undergone mitral valve replacement by using dobutamine stress echocardiography
      (DSE) and to evaluate the relationship between the size of the prosthetic valve
      and cardiac recovery-remodeling process. METHODS: Thirty-nine patients, who had
      undergone mitral valve replacement were compared in terms of left ventricular
      diameters, systolic functions and cardiac mass indexes in order to investigate
      the effect of the mechanical valve size on postoperative cardiac remodeling in
      this longitudinal study. They were divided into three groups according to their
      valve size: Group 1 (valve size<29 mm, n=11), Group 2 (valve size=29 mm, n=11)
      and Group 3 (valve size>29 mm, n=17). Statistical analysis was performed using
      Chi-square and one-way ANOVA tests to determine the statistical differences
      between the groups. The repeated measurements of two-way ANOVA test was used to
      analyze effects during long-term follow-up. RESULTS: Only Group 1 patients
      achieved a significant decrease in terms of left ventricular mass index and end
      diastolic diameter (138.3+/-29.7 g/m2 vs 86.6+/-15.6 g/m2 and 5.1+/-0.5 cm vs.
      4.4+/-0.4 cm, p<0.05). Group 3 patients' left ventricular ejection fraction
      become worse after the operation (64.0+/-5.6% vs. 55.9+/-6.5%, p<0.05). Maximum
      and mean pressure gradients across the mitral prosthesis as well as pulmonary
      artery pressure were significantly increased in all groups during DSE. Maximum
      gradients increased from 14.2+/-4.6 to 20.7+/-7.5 mmHg in Group 1 (p<0.05),
      11.6+/-4.7 to 16.2+/-6.8 mmHg in Group 2 (p<0.05), and 10.6+/-3.1 to 20.8+/-12.7
      mmHg in Group 3 (p<0.05). Isovolumic relaxation time decreased in all groups
      following the dobutamine infusion, as expected, but this decline was not
      significant in Group 3. CONCLUSION: A worsening in left ventricular systolic
      function was observed in large- sized valve prosthesis group. Only the patients
      who had undergone MVR with small-sized valve prosthesis achieved a decrease in
      cardiac mass index and preservation of the systolic function. The
      echocardiographically determined differences and mass index that appeared after
      the operation may point out that, the effect of the operation on cardiac
      remodeling can be related with the ventricular size.

PMID- 18065337
TI  - Dietary polyphenol quercetin protects rat hearts during reperfusion: enhanced
      antioxidant capacity with chronic treatment.
AB  - OBJECTIVE: Quercetin is an important member of dietary flavonoid family and
      widely present in red wine and Mediterranean diet. The major objective of the
      this study is to evaluate the beneficial effects of quercetin in protecting the
      myocardium from the deleterious effects of ischemia reperfusion (I/R) injury in
      chronic quercetin treatment with or without an acute quercetin infusion
      protocols. METHODS: Forty male Sprague-Dawley rats were included in this
      experimental randomized study/ Langendorff perfused isolated rat hearts were
      subjected to 60-min of global ischemia period following 60-min of reperfusion.
      All animals were randomly divided into 4 groups. Group 1 animals were kept as
      controls. Group 3 and 4 animals received 50 mg/kg quercetin via an intragastric
      tube for 7 days for chronic treatment. Group 2 and 4 animals received an acute 15
      mmol/L infusion for 30 minutes before the onset of ischemia. The myocardial
      postischemic recovery was compared using hemodynamic data (peak systolic
      pressure, end-diastolic pressure and +dP/dtmax), coronary flow, biochemical
      parameters (lactate dehydrogenase, creatine kinase-MB fraction, cardiac troponin
      I) from coronary effluent, and oxidative stress markers (malondialdehyde,
      glutathione, glutathione reductase and nitrite) from heart tissue homogenates in
      each group. RESULTS: Quercetin has provided increased preservation in myocardial
      recovery in both chronic and acute treatment protocols compared to non-treated
      group. According to all estimated hemodynamic parameters, while the statistical
      difference between acute treated hearts and control hearts was significant
      (p<0.05); this significance was more clear in chronic treated groups (group 3 and
      4) when compared to control (p<0.01). Likewise, biochemical and oxidative stress
      markers displayed significant differences in acute treated and chronic treated
      hearts when compared to control (p<0.05 and p<0.01, respectively). CONCLUSION: As
      a major dietary flavonoid, due to its antioxidant and cytoprotective actions,
      quercetin has the capacity to protect the myocardial tissue against global
      ischemia and reperfusion injury. In instances where the molecule is administered
      for the purpose of acute therapy, this cardioprotective effect of a significant
      degree can be observed to; however, this potency is further accentuated upon
      administration as a chronic treatment protocol for seven days.

PMID- 18065338
TI  - Does cardiopulmonary bypass change serum neuron-specific enolase levels?
AB  - OBJECTIVE: The effects of cardiopulmonary bypass (CPB) on serum neuron-specific
      enolase (NSE) levels in patients without cognitive dysfunction and neurological
      deficit are not yet clarified. This study was designed to see the sole effect of
      extracorporeal circulation on serum NSE levels in patients without any clinically
      observed neurological deficit. METHODS: Thirty-two consecutive patients
      undergoing first elective open-heart surgery were included in this prospective
      study. Neurological status was assessed by clinical examination before surgery,
      and on the postoperative first and second days. Blood samples were obtained after
      anesthesia induction before the administration of heparin, within the first hour
      post CPB, 24 and 48 hours after the end of operation. Each blood sample was
      assayed for hemoglobin (Hb), hematocrit and NSE levels. The Friedman's Test to
      compare the serial measurements of NSE and hemoglobin samples and the post-hoc
      Tukey test for paired comparisons between pre and postoperative values were
      applied Pearson correlation test was used to examine the correlation between NSE
      concentration and aortic cross-clamping time and CPB time, age, postoperative
      hematocrit and hemoglobin levels and the amount of blood products transfusion.
      RESULTS: There were no significant differences between NSE values at any sampling
      time: 11.6+/-8.0 mg/dL, 8.7+/-4.7 mg/dL, 9.3+/-5.4 mg/dL and 8.9+/-5.8 mg/dL,
      measured preoperatively, at the end of operation, on the first and second post
      operative days, respectively. There was no significant correlation between NSE
      values with any of the compared variables including CPB time. CONCLUSION: This
      study demonstrated that the possible damage of CPB on central nervous system and
      on blood cells did not reach to the extent of causing any significant increase in
      serum NSE levels in non-complicated patients undergoing open-heart surgery.

PMID- 18065339
TI  - Serum lipid profiles including non-high density lipoprotein cholesterol levels in
      Turkish school-children.
AB  - OBJECTIVE: Early detection of dyslipidemia and long-term prevention of
      atherosclerosis by controlling risk factors should begin in childhood. The
      purpose of this study was to evaluate the prevalence of dyslipidemia according to
      non-high density lipoprotein cholesterol (non-HDL-C) levels in children and also
      evaluate serum non-HDL-C levels according to age groups, gender difference and
      living areas. METHODS: Overall, 2896 children (1467 girls, 1429 boys) aged
      between 7-18 years, residing in urban and rural parts of Eskisehir, Turkey, were
      enrolled in this randomized cross-sectional study. Serum non-HDL-C, total
      cholesterol (TC) and triglyceride (TG) levels were assessed in all participants
      of the study. Statistical analysis was performed Student's independent-samples T
      test for comparison of lipid parameters and relations between lipid parameters
      and age, anthropometric measurements, body fat percentage were evaluated by
      Pearson correlation test. RESULTS: Serum non-HDL-C levels were significantly
      higher in girls (115.5+/-31.5mg/dl) than boys (106.7+/-30.2 mg/Dl) (p<0.001). For
      girls, serum non-HDL-C levels were higher in 7-10 year age group than in 11-14
      year and 15-18-year age groups (p<0.01 and p<0.05, respectively). For boys serum
      non-HDL-C levels of 7-10 year age group were significantly higher than in 11-14
      year and 15-18-year age groups (p<0.001 for both). Serum non-HDL-C, total
      cholesterol and triglyceride levels were higher in girls than in boys especially
      in the 7-10-year-old age group. Serum TC, LDL-C, and HDL-C levels were higher in
      urban area residents, while serum TG levels were higher in rural area residents
      (p<0.001). Serum non-HDL-C levels were similar in residents of different living
      areas (p>0.05). In both sexes, non-HDL-C levels positively correlated with age
      and lipid parameters except HDL-C levels and also negatively correlated with HDL
      C levels. In boys, non-HDL-C levels also correlated with total body fat
      percentage, weight, height. The prevalence of dyslipidemia according to non-HDL-C
      levels was higher (13.2%) in girls than boys (8.9%) (p<0.001). The prevalence of
      elevated non-HDL-C levels was higher in urban area residents than in rural area
      residents (p<0.05). The dyslipidemia prevalence according to non-HDL-C levels was
      similar with dyslipidemia prevalence according to serum LDL-C levels. CONCLUSION:
      Our results are indicative of the prevalence of dyslipidemia in children is
      considerably common in our population. Serum non-HDL-C levels could be used as an
      appropriate tool for detecting dyslipidemia in childhood.

PMID- 18065340
TI  - Dyslipidemia in school-children.

PMID- 18065341
TI  - [Sexual activity and cardiovascular risk].
AB  - Assessment and treatment of sexual dysfunction gain more importance in countries
      like Turkey where cardiovascular events are frequently seen in young adults. The
      mortality of cardiovascular events is reduced by primary percutaneous coronary
      angioplasty (PTCA), use of new thrombolytics in acute myocardial infarction (MI),
      and new drugs used in the treatment of heart failure. Because of the longer life
      expectancy, assessment of sexual functions and rehabilitation are getting more
      important in these patients. Since phosphodiesterase type 5 inhibitors (PDE 5)
      have been frequently utilized in the treatment of impotence, patients' and the
      doctors' attention have been directed towards cardiovascular risks of sexual
      activity. In recent years, this topic has become more important because several
      reports have stated the possible relationship between the use of PDE5 inhibitors
      and myocardial infarction. It is known, that in patients with cardiovascular
      diseases, sexual activity poses a low sudden death risk independent of PDE5
      inhibitor use. In this review, the points that doctors should take into account
      while considering and treating the sexual dysfunction in patients with
      cardiovascular diseases are discussed.

PMID- 18065342
TI  - [A survey of heart tumors: clinical and echocardiographic approach].
AB  - Heart tumors can be primary in origin, can develop from direct extension of a
      neighboring tumor or they can be the manifestation of metastasis of a distant
      tumor. Myxomas are the most frequently encountered primary benign cardiac tumors.
      Primary malignant tumors of the heart are rare, and they are mostly sarcomatous
      in structure. Secondary heart tumors constitute a wide spectrum, nevertheless
      they most frequently originate from lung cancer, breast cancer and hematological
      malignancies. Heart tumors may involve myocardium, endocardium, epicardium,
      pericardium, or any combination of the aforementioned layers. On the other hand,
      the usual site for metastasis to the heart is the pericardium. These tumors do
      not have a well- established classification. Clinical findings are usually non
      specific and transient in nature and frequently present late in the disease
      process. Transthoracic and transesophageal echocardiography are the most widely
      used diagnostic modalities. Magnetic resonance imaging and computerized
      tomography may be helpful for selected cases. Surgery is the principal
      therapeutic option in benign tumors and when recurrences are not taken into
      account, they have favorable prognoses. Since surgical resection is usually
      incomplete in malignant tumors, therapy must be individualized for each patient;
      even with adjuvant chemotherapy, postoperative survival is usually short.
      Metastases to the heart are usually approached symptomatically except for
      exceptional cases.

PMID- 18065343
TI  - Spontaneous coronary artery dissection: a long-term follow-up.

PMID- 18065344
TI  - Pacemaker lead failure due to crush injury.

PMID- 18065345
TI  - [A cardiac hydatid cyst case seen after operation on pulmonary hydatid cyst].

PMID- 18065346
TI  - Three-year follow up of recurrent cardiac echinococcosis simulating myxoma:
      report of a rare case.

PMID- 18065347
TI  - Coronary bypass surgery in essential thrombocythemia.

PMID- 18065348
TI  - Two-stage successful surgery in an aortic coarctation case operated initially for
      ascending aortic aneurysm.

PMID- 18065349
TI  - Angiotensinogen M235T gene polymorphism in essential hypertension/angiotensinogen
      M235T polymorphism and left ventricular indices in treated hypertensive patients
      with normal coronary arteries.

PMID- 18065350
TI  - [Patient education and exercise in cardiac rehabilitation].

PMID- 18065351
TI  - [Atrial septal defect closure with Solysafe device: first experience in Turkey].

PMID- 18065352
TI  - [Natriuretic peptide family as a "novel candidate marker" for the assessment of
      diagnosis, therapeutic response and prognosis in cardiovascular disease].

PMID- 18065353
TI  - An unusual cause of syncope: hyperthyroidism.

PMID- 18065354
TI  - [Ventricular septal rupture and cardiogenic shock in the myocardial infarction
      case presenting with fever and leukocytosis].

PMID- 18065355
TI  - [Atrioventricular reciprocating tachycardia induced by electrical injury].

PMID- 18065356
TI  - [Total sternal cleft: computerized tomography findings].

PMID- 18065357
TI  - [Intraoperative appearance of a homograft aortic valve 16 years after the
      implantation].

PMID- 18065358
TI  - [Mitral valve replacement in a renal transplant patient].

PMID- 18065359
TI  - Live three-dimensional transthoracic echocardiography in the assessment of the
      papillary muscle abnormality with mitral regurgitation.

PMID- 18065360
TI  - [Case of Phlegmasia cerulea dolens as a rare complication in deep venous
      thrombosis].

PMID- 18065361
TI  - [Spontaneous cholesterol embolism confused with peripheral arterial disease].

PMID- 18065362
TI  - Aortic aneurysm: a rare complication of ulcerative colitis.

PMID- 18065363
TI  - Spontaneous dissection of left anterior descending artery and cardiac apical mass
      without aneurysm.

PMID- 18065364
TI  - [Natural orifice transluminal endoscopic surgery].
AB  - In Natural Orifice Transluminal Endoscopic Surgery (NOTES) a flexible endoscope
      is passed through a natural orifice of the body and intra-abdominal procedures
      can be performed through a transvisceral (transgastric, -colonic, -vaginal or 
      vesical) incision. Principally, this state-of-the-art technology decreases
      invasiveness and postoperative pain, prevents postoperative hernia formation and
      improves cosmetic results. However, numerous questions regarding the technique
      are unanswered yet. Further research is necessary to extend the armamentarium of
      minimally invasive surgery. This article reviews the current state of
      experimental results and clinical approaches of NOTES.

PMID- 18065365
TI  - [Surgical treatment options of metastatic tumours in the gastrointestinal tract
      (stomach, small and large bowel)].
AB  - Metastatic tumours in the gastrointestinal tract are infrequent findings and
      usually represent advanced disease at the time of their diagnosis. In these
      cases, radical surgical resection is rarely possible due to dissemination, but
      palliative surgery can be relatively effective. Operative treatment can be
      indicated as a life saving measure in patients with gastrointestinal bleeding,
      perforation or obstruction. Radical resection of metastases may prolong survival,
      if R0 resection is achieved. In these disease free patients, the surgical
      treatment should be tailored to the primary tumour and combined with neoadjuvant
      or adjuvant therapy. 1053 gastrointestinal tumours were treated surgically by the
      authors between 01.01.2000. and 31.12.2005. Of those, secondary tumours were
      found in 24 cases in the gastrointestinal tract (11 in the stomach, nine in the
      small bowel and four in the large bowel). The authors summarize their experience
      and review the relevant literature.

PMID- 18065366
TI  - [Rectum carcinomas treated with Kraske procedure in elderly patients].
AB  - Kraske procedure is an option that can be chosen to treat rectal tumours in
      elderly patients with multiple co-morbidities, in order to minimize complications
      and stress caused by surgery. In the past six years, 382 rectal resections were
      performed in our department: 154 abdominoperineal rectum resections, 219 anterior
      rectum resections and 9 Kraske procedures in high anaesthetic risk patients.
      Kraske resection was applied for mid- and lower third rectal cancers, providing a
      short term survival for more than half of these patients. The authors discuss
      their experience with the Kraske procedure.

PMID- 18065367
TI  - [Late complication after mesh repair of incisional hernias: pseudocyst
      formation].
AB  - INTRODUCTION: Using mesh for hernia repair is a very common procedure; they are
      particularly useful for postoperative incisional hernias. The most common
      complications of mesh repair are seroma, haematoma or abscess formation. Previous
      literature data suggested that fibrotic cyst formation appearing in the late
      postoperative period is relatively rare. However, more recent studies and our own
      experience indicate that its incidence is more common and we have to consider it
      in the differential diagnosis of the complications of hernia repair. PATIENTS:
      148 incisional hernia mesh repairs were carried out between a period of 1st
      January, 2001 to 31st December, 2005. Fibrotic pseudocyst formation was observed
      in five cases. All developed as a late complication between 4 to 25 months
      postoperatively. An onlay polypropylene mesh was used in each case. All five
      patients underwent a wide excision of the pseudocyst wall and they recovered
      without complications. DISCUSSION: The etiology of pseudocyst formation is
      unclear. Nevertheless, a possible relationship between the development of seroma
      and haematoma can not be ruled out, despite no fibrotic pseudocyst formation was
      observed in the early postoperative period. There is no evidence whether the
      characteristics of the mesh or the way of implantation would have any effect on
      pseudocyst formation, as well. It is noted that the only treatment of this late
      complication is surgical excision. Pseudocyst formation might be prevented by the
      application of sublay and minimally invasive techniques.

PMID- 18065368
TI  - [A comparative clinical study of the treatment of hypertrophic scars with either
      intralaesional steroid or silicone gel sheeting].
AB  - The linear (or "surgical") hypertrophic scar is the most common type of
      pathologic scarring. There has been a steady increase in the number of patients
      with hypertrophic scars over the years due to the rising number of operative
      interventions altogether. However, the therapeutic protocols are not homogeneous
      and they show significant variations. 200 cases with hypertrophic scars were
      treated by the authors from April 2001 to March 2004. 24 patients were selected
      in the study from these cases; and two randomized groups were formed. Each group
      included 12-12 patients, who were treated with either intralaesional steroid or
      silicone gel sheeting. The therapeutic protocols were defined by the authors. The
      aim of this study was to compare and determine the roles of these two commonly
      used treatment options of hypertrophic scars. The authors present patient
      demographics; and analyze the results and outcome of the study. Both methods were
      efficient significantly, however intralaesional steroid therapy had a more rapid
      effect and it lasted longer than silicone gel sheeting. These results confirmed
      the role of these two treatment modalities in the protocols. The authors
      concluded that silicone gel sheeting is the first line, while intralaesional
      steroid is the second line treatment for primary linear hypertrophic scars. Based
      on the authors' experience, in recurrent linear hypertrophic scars,
      intralaesional steroid therapy is recommended in first line, because silicone gel
      sheeting was largely ineffective. Prospective randomized clinical trials should
      be needed to further clarify their role in the treatment protocols.

PMID- 18065369
TI  - [Pathology and diagnostic opportunities of lower limb compartment syndrome].
AB  - BACKGROUND: The indication for the surgical treatment of lower limb compartment
      syndrome mostly depends on the clinical signs, which can be uncertain and often
      delayed, resulting in a late and insufficient intervention. AIM: In this study,
      the progression of compartment syndrome was monitored with the measurement of
      intracompartmental pressure and tissue oxygen saturation. MATERIALS AND METHODS:
      16 patients (12 male and 4 female; mean age: 62,7 years) underwent acute lower
      limb revascularization surgery due to critical (more than 4 hour) limb ischaemia.
      The indications were the following: 5 iliac artery embolisms and 11 femoral
      artery occlusions. After revascularization, significant lower limb oedema and
      swelling were detected. To monitor the elevated intracompartmental pressure
      (ICP), KODIAG pressure meter was used. Tissue oxygen saturation (StO2) was
      measured with near-infrared-spectroscopy. RESULTS: In 12 cases the IPC exceeded
      the critical 40 mmHg. In these patients, StO2 was 50-53%, in spite of the
      successful re-canalisation. An urgent, semi-open fasciotomy was performed in
      these cases. In four patients, the clinical picture suggested compartment
      syndrome. However, the measured parameters did not indicate surgical intervention
      (ICP: 25-35 mmHg, StO2: normal). SUMMARY: In addition to the empirical
      guidelines, we describe an evidence based surgical intervention strategy for
      lower limb compartment syndrome. Our results and advised parameter intervals help
      the clinicians to decide between conservative and operative treatment of the
      disease.

PMID- 18065370
TI  - [Solitary oesophageal metastasis of breast cancer after 17 years latency].
AB  - The authors discuss a case of a 63-year-old woman, who presented with dysphagia,
      17 years after radical mastectomy for breast cancer. CT scan showed a juxta
      esophageal mediastinal tumour. A biopsy via right thoracotomy revealed a
      metastatic adenocarcinoma of the oesophageal wall from the previous breast
      carcinoma. Minimally invasive oesophageal intubation was used for palliation.
      Hormonal manipulation and radiotherapy was commenced postoperatively. The patient
      was well after eight months follow-up. A combination of high clinical suspicion
      with EUS and deep oesophageal biopsy can lead to the correct diagnosis of this
      very rare clinical entity. The biology of metastatic breast cancer may demand
      palliation by oesophageal intubation or stenting combined with adjuvant chemo,
      radio or hormonal therapy in such instances.

PMID- 18065371
TI  - [Videothoracoscopic removal of ectopic liver].
AB  - Authors present a case of an ectopic liver in the chest of a 14 year-old female
      patient. The lesion was discovered by screening chest X-ray and was consequently
      removed by videothoracoscopic surgery. A brief literature review was carried out,
      too.

PMID- 18065372
TI  - [Lajos Petz died 75 years ago].

PMID- 18065374
TI  - [MicroRNAs and cancer-associated signal transduction pathways].
AB  - Signal transduction pathways play extremely important roles in various processes
      of cell life including metabolism, growth, proliferation, stress, development and
      apoptosis. Disruption of these pathways may affect normal cell growth and
      development, and even gives rise to tumors. MicroRNAs (miRNAs) are a newly
      discovered class of non-coding small RNAs (approximately 22 nucleotides in
      length) in eukaryotes that negatively regulate gene expression at the post
      transcriptional level. With a wide range of target genes, they play essential and
      pervasive roles in diverse biological processes. Aberrant miRNA expression has
      recently been discovered in tumor development, indicating that miRNAs may be
      connected with tumorigenesis, possibly through regulating the expression of
      oncogenes and tumor-suppressing genes. It has also been noticed that many target
      genes of miRNA can influence tumor associated signal transduction pathways. The
      significant roles of miRNAs in tumorigenesis indicate that they may become a
      powerful tool for diagnosis and treatment of human cancers in the future.

PMID- 18065376
TI  - [Constructing gene regulatory network from microarray data].
AB  - With the rapid deposition of the microarray data in recent years, microarray data
      has increasingly become an important data source for bioinformatics research.
      Based on microarray date, constructing gene regulatory networks has also become a
      hotspot. By constructing the gene regulatory network, we can identify the
      complicated regulatory relationships, uncover the regulatory patterns in the
      cell, and gain the systematic view for biological process. Recently, many
      algorithms have also been introduced in this field to determine gene regulatory
      networks based on such high-throughput microarray data. In this paper, we review
      the development of these algorithms, with a particular emphasis on their
      improvement of theory and method. At last, we present the available software and
      platform and discuss the development trends in this field.

PMID- 18065375
TI  - [Mitochondrial and oocyte development].
AB  - Oocyte development and maturation is a complicated process. The nuclear
      maturation and cytoplasmic maturation must synchronize which can ensure normal
      oocyte fertilization and following development. Mitochondrial is the most
      important cellular organell in cytoplasm, and the variation of its distribution
      during oocyte maturation, the capacity of OXPHOS generating ATP as well as the
      content or copy number or transcription level of mitochondrial DNA play an
      important role in oocyte development and maturation. Therefore, the studies on
      the variation of mitochondrial distribution, function and mitochondrial DNA could
      enhance our understanding of the physiology of reproduction and provide new
      insight to solve the difficulties of assisted reproduction as well as cloning
      embryo technology.

PMID- 18065377
TI  - [The application of statistical approaches in studying population genetics with
      STR data].
AB  - As high polymorphism markers, STR loci have been widely used in studying
      population genetics. This review summarizes various genetic diversity parameters
      and analysis methods regarding to genotype frequency and allele frequency,
      including heterozygosity, polymorphism information content (PIC), linkage
      disequilibrium coefficients, inbreeding coefficients, genetic distance and
      fixation indices. The methods of statistical analysis included principal
      component analysis, phylogenetic trees, analysis of molecular variance (AMOVA), R
      matrix, GIS and spatial autocorrelation. By means of various parameters and
      methods, graphically and scientifically, we can describe and interpret several
      key issues in the study of population genetics, such as population genetic
      structure, population differentiation and human evolution.

PMID- 18065378
TI  - [DOT1: a distinct class of histone lysine methyltransferase].
AB  - Lysine methylation is an important covalent modification of histone and has
      fundamental and divers roles in biological processes including regulation of
      chromatin structure dynamics and gene expression. Recently, a distinct class of
      histone lysine methyltransferase DOT1 was found to methylate histone H3 lysine79
      (H3K79) residue, which is located on the accessible face of the core nucleosome.
      The DOT1 proteins do not contain a SET domain, a conserved sequence motif found
      in all previously characterized histone H3 lysine methyltransferases that act on
      the histone N-termianl tail. The characteristics of DOT1 proteins and H3K79
      methylation suggest that they may have important and characteristic functions.
      Here, we summarize recent advances in specific structure of DOT1 protein,
      biological functions of DOT1 proteins and H3K79 methylation and trans-histone
      regulatory1 between histone H2B ubiquitination and H3K79 methylation.

PMID- 18065379
TI  - [Analysis of genetic polymorphisms of 10 STR loci on chromosome 11 in a Shaanxi
      Han population].
AB  - D11S1760, D11S4102, D11S4116, D11S4207, D11S4162, D11S914, D11S4127, D11S917,
      D11S4146 and D11S915 of 10 short tandem repeat (STR) loci on chromosome 11 were
      analyzed by fluorescence-based gene scan technique to understand the genetic
      polymorphisms of those STR loci on chromosome 11 in a Han population in Shaanxi
      province. The results showed that the number of alleles and genotypes observed at
      loci D11S1760, D11S4102, D11S4116, D11S4207, D11S4162, D11S914, D11S4127,
      D11S917, D11S4146 and D11S915 were 17, 11, 15, 11, 4, 6, 7, 12, 11 and 13 for
      alleles and 41, 18, 36, 30, 8, 10, 16, 30, 29 and 32 for genotypes, respectively.
      All the 10 loci were in Hardy-Weinberg equilibrium. The heterozygosities of each
      STR locus was 86.72%, 67.95%, 83.90%, 85.96%, 58.18%, 57.63%, 72.60%, 72.73%,
      77.87% and 86.40%. It concluded the 10 loci on chromosome 11 were relatively
      highly genetic polymorphic in Han populations and could provide useful markers
      for genetic studies.

PMID- 18065380
TI  - [Development and forensic application of a pentaplex X-STR loci typing system].
AB  - A fluorescent multiplex PCR that simultaneously amplifies five X-chromosomal
      short tandem repeat (X-STR) loci (DXS6803, DXS981, DXS6809, DXS6789 and
      DXS7132)was set up to study their polymorphic nature and to determine its use in
      kinship tests for forensic cases. PCR products were analyzed using capillary
      electrophoresis and ABI prism 3100 Genetic Analyzer with GeneMapper ID 3.1
      Analysis Software. The pentaplex system gave satisfactory results as its
      sensitivity, reproducibility and unambiguous genotyping. About 20 ng DNA was
      routinely used, although 0.25 ng DNA was sufficient for allele typing. The
      results demonstrate that the multiplex system of the five X-STR loci provides a
      fast technology for forensic identification and paternity testing. The X-STR
      pentaplex system can complement the analysis of AS-STR and Y-STR efficiently,
      especially in complex cases of kinship testing.

PMID- 18065381
TI  - [Analysis of the genetic structure of 12 Chinese and foreign cattle breeds using
      DNA microsatellite markers].
AB  - The genetic diversity of 9 Chinese native cattle breeds and 3 introduced breeds
      were analyzed using 12 microsatellite DNA markers recommended by the Food and
      Agriculture Organization of the United Nations (FAO) and the International
      Society of Animal Genetics (ISAG) through fluorescence-multiple PCR. According to
      the allele frequencies of 12 microsatellite locus, mean heterozygosity (H),
      polymorphism information content (PIC) , DA and DS genetic distances were
      calculated for each breed. Cluster analysis based on UPGMA method indicated that
      12 breeds were clustered into four groups. Group I belonged to the southern-China
      cattle including Enshi, Liping, Zhaotong and Chuannan Mountainous; Group II
      belonged to the central-China cattle including Jiaxian Red and Zaosheng, Pinglu
      Mountainous; Group III belonged to the northern-China cattle including Yanbian
      and Changbai; Group IV consisted of foreign breeds including Germany Yellow,
      Simmental and Charolais. The results may provide an academic basis for
      preservation and utilization of Chinese native cattle breeds.

PMID- 18065382
TI  - [A method for detecting bovine leukocyte adhesion deficiency in Holstein calves
      using polymerase chain reaction-single strand conformation polymorphism
      analysis].
AB  - Bovine leukocyte adhesion deficiency (BLAD) is an autosomal recessive disease
      caused by A-->G mutation in the CD18 gene. The disease is characterized by
      greatly reduced expression of the heterodimeric beta2 integrin adhesion molecules
      on leukocytes, resulting in multiple defects in leukocyte function and
      significant deficits on performance traits in Holstein cattle. In this study,
      primers were designed to amplify the CD18 gene fragment and BLAD was detected by
      PCR-SSCP in a simple, highly accurate and high throughput manner. Results were
      confirmed by DNA sequencing. This study provides a more reliable and useful
      method for extensive screening of BLAD and also offers a theoretical basis for
      molecular diagnosis in Holstein calves.

PMID- 18065383
TI  - [Construction of genetic linkage map and QTL detection of chromosome 3 in sheep].
AB  - Based on the reference family of Sichuan liangshan semi-fine sheep, the genetic
      linkage map was constructed by Crimap 2.4 software, which was used to detect the
      QTLs for growth traits by QTLExpress with nine microsatellite markers located on
      chromosome 3 in sheep. The results indicated that: (1) the mean of the
      polymorphic information content was 0.606 (0.378-0.738), and the mean
      heterozygosity was 0.650 (0.404-0.766); (2) the length of the linkage map was
      339.8 cM, which was longer than the length of map built by the international
      major drawing organization for sheep with the average distance of markers of 42.5
      cM; (3) The QTLs for weaning weight, weaning daily gain, and 2.5 year weight were
      detected at 99 cM, 219 cM, 273 cM, respectively. The effect of QTLs on weaning
      daily gain trait and 2.5 year weight trait were significant, except for weaning
      weight trait.

PMID- 18065384
TI  - [Association between single nucleotide polymorphism of ADFP gene and carcass
      traits and intramuscular fat content in chicken].
AB  - In order to investigate the effect of ADFP gene on the carcass traits and
      intramuscular fat content of Da-heng high-quality chicken, we analyzed the coding
      sequence of the ADFP gene by single-strand conformation polymorphism (SSCP) and
      DNA sequencing in five pure lines and three crossbreds. We found three single
      nucleotide polymorphism sites, including A/T at base position 4,079 (locus A),
      C/T at base position 4,843 (locus B) and A/G at base position 7,070 (locus C).
      GLM analysis for the effect of genotypes on carcass traits and intramuscular fat
      content demonstrated a significant effect on leg muscle percentage, abdomen fat
      weight, abdominal fat percentage and intra-muscular fat content in locus A (P <
      0.05), a significant association with living body weight and carcass weight for
      locus B (P < 0.05) and a significant association with breast muscle weight and
      intramuscular fat content (P < 0.05), and a very significant association with
      breast muscle percentage for locus C (P < 0.01). It was concluded that ADFP gene
      may be a major gene or linked to such a gene that affects the fat traits of
      birds. Polymorphic loci A and C could be used as molecular markers for abdominal
      fat weight, abdominal fat percentage and intramuscular fat content in birds in
      future studies.

PMID- 18065385
TI  - [Cloning and bioinformatics analysis of SLA-DR genes in Hunan Shaziling pigs].
AB  - In order to clone class II DRA and DRB genes of swine leukocyte antigen (SLA) in
      Hunan Shaziling pigs, to analyze their characteristics and polymorphism and to
      provide immunological basic parameters for xenotransplantation from pigs to
      humans. SLA-DRA and SLA-DRB genes in two Shaziling pigs with the absence of
      porcine endogenous retrovirus (PERV) env-c were amplified by RT-PCR, cloned into
      PUCm-T vectors, sequenced and analyzed through BLAST in NCBI and related software
      in ExPASY. The obtained SLA-DRA and SLA-DRB genes of Shaziling pigs were 1,177
      and 909 nucleotides in length with their accession numbers in Genbank as EF143987
      and EF143988. Bioinformatics analyses have shown that they both contain opening
      reading frame (ORF) and encode 252 and 266 amino acids respectively. Comparing
      the ORF and protein sequences of the Shaziling SLA-DRA and SLA-DRB genes with
      their counterpart sequences of human, the homologies of nucleotide sequences were
      83% and 83%, and the homologies of amino acid sequences 83 % and 79%
      respectively. Further comparison with SLA sequences published in GenBank
      indicated that SLA-DRB gene found in Shaziling pigs has polymorphism while the
      homology of SLA-DRA gene is up to 100 % .

PMID- 18065386
TI  - [Genetic polymorphism of FSH b subunit gene and correlation with reproductive
      traits in Beijing Black Pig].
AB  - FSH beta subunit gene was regarded as a candidate gene for reproductive traits of
      Beijing Black Pig in this study. The polymorphism of two loci FSHbeta-1 and
      FSHbeta-2 was detected by electrophoretic method and PCR-RFLP with restriction
      endonuclease Hae III. Sequencing results showed that a 273 bp sequence, which was
      a retrotransponsons including a RNA Polymerase III inter promoter, was inserted
      between the 134th and 135th nucleotide of the PCR product in FSHbeta-1, and the
      mutation (C-->T) was revealed at the 173th nucleotide of the PCR product in
      FSHbeta-2. Both alleles (A and B) of both loci were found in the population that
      showed low polymorphism. Chi-square test indicated that the two polymorphism
      sites fitted Hardy-Weinberg equilibrium (P>0.05). The effects of polymorphism of
      FSH b subunit gene on total born number (TNB), number born alive (NBA), and birth
      weight (WB) were analyzed. For FSHbeta-1 locus, pigs of the first parity with
      genotype AA had 0.96 and 1.85 TNB more than those with genotypes AB and BB. The
      pigs of the first parity with genotypes AA and AB had 0.95 and 1.69 NBA more than
      those with genotype BB, respectively. For FSHbeta-2 locus, pigs of the first
      parity with genotype AA had1.57 and 2.15 TNB more than those with genotypes AB
      and BB. The pigs of the first parity with genotypes AA and AB had 1.00 and 0.94
      NBA more than those with genotype BB, respectively. The pigs of multiparous with
      genotype AA had 0.25 kg of WB more than those with genotype BB. The results of
      combined genotype effects indicated that A allele of FSHbeta-1 locus in all the
      population and FSHbeta-2 locus in pigs of the first parity had the positive
      effective on TNB, NBA, and WB.

PMID- 18065387
TI  - [Cloning and sequence analysis of alpha satellite DNA in Arctic fox].
AB  - Genomic DNAs from Arctic fox were cleaved with restriction enzymes. The prominent
      ethidium-bromide stanined bands were cloned and sequenced after separation of DNA
      fragments by agarose gel electrophoresis. Forty-two satellite sequences were
      obtained by sequencing. Sequence analyses revealed that the satellite monomer in
      length was 737 bp, with an average G+C content of 51.9%. There were 91%-97%
      homology among the monomers, and the monomer consisted of three subrepeats of
      approximately 245 bp in length with 51%-54% homology. The satellite DNAs were
      specific for canidae, and had 74% homology to the dog centromere-associated
      nucleotide sequences. In order to distinguish from another satellite DNAs of
      canidae genome, the satellite was designated as alpha satellite DNA.

PMID- 18065388
TI  - [Genetic potential analysis of Germany mirror carp (Cyprinus carpio L.) using
      microsatellite markers].
AB  - Using 30 microsatellite markers and combining quantity characters such as body
      weight, body size and body width, we evaluated the genetic potential of 3 Germany
      mirror carp populations. Number of effective alleles (Ae), observed (Ho) and
      expected (He) heterozygosity values and polymorphic information contents (PIC)
      were all calculated. 287 alleles and 559 genotypes were detected. The DNA
      fragment length was 109-400 bp. The Hardy-Weinberg Equilibrium was checked and
      phenomenon of some disequilibrium were studied according to the test of c2. The
      result showed that the level of genetic variability was moderate, but genetic
      potential of Shuanglai population was much lower than that Huanxin and Songpu
      breeding populations. Polymorphic Information Contents (PIC) of the 3 populations
      of Germany mirror carp were between 0.08787 and 0.5377, both of highly and
      moderately polymorphic markers were 13. The number of effective alleles (Ae) were
      between 1.1014 and 6.4665. The observed (Ho) and expected (He) heterozygosity
      values were 0.0968-0.9892 and 0.0926-0.8554 respectively. The linkage correlation
      was analyzed using data of body weight, body size and body width and 30 loci. The
      result shown that there existed 2 loci, HLJ319 and HLJ693 associated with body
      size. The HLJ693 locus significantly correlated with body weight character. The
      HLJ677 locus linked with body width. And then the result were verified in
      Recombinant Inbred Lines (RIL) of common carp. It shown that the HLJ319 locus was
      significantly linked with body size, the same as the result of common carp QTL
      location.

PMID- 18065389
TI  - [Adaptive evolution of chemokines and their receptors genes].
AB  - Branch-Site Model is a statistical method for detecting molecular adaptation at
      individual along specific lineages. Not only the model could indicate whether
      genes in phylogeny under the positive selection or not, but also could forecast
      positive selection sites in these genes. The sites promote divergence and
      polymorphism of genes. Chemokines are chemotactic cytokines that can induce
      immune cells migration, conducting their functions via chemokine receptors. In
      the test, the molecular adaptation of chemokines and chemokines receptors genes
      had been analyzed by Branch-Site model. The results showed that only a few of
      genes, such as RANTES and CCR5, are in the course of positive selection. Several
      CCR5 positive selection sites are located in a region that involved in binding to
      receptor and its chemokine.

PMID- 18065390
TI  - [Identification and expression analysis of a full-length cDNA encoding Brassica
      napus small nuclear ribonucleoprotein BnSmD1].
AB  - By using substractive hybridization (SSH) and rapid amplification of cDNA ends
      polymerase chain reaction (RACE-PCR), a full-length cDNA encoding Brassica napus
      small nuclear ribonucleoprotein, named BnSmD1, was obtained. It had 484 base
      pairs in length containing an open reading frame (ORF) of 354 bp and encoding a
      predicted protein of 118 amino acids with a molecular weight of 13 kDa. The
      BnSmD1 protein shares two highly conserved Sm folds (Sm-1 and Sm-2) and a C
      terminal RG dipeptide repeat. Northern blot analysis revealed that BnSmD1 was
      expressed in all tested organs in B. napus, but its transcript level in early
      floral buds was much higher than that in leaf and stem tissues. No obvious
      expression difference was observed in leaf and stem tissues between the apetalous
      line Apet33-10 petalled near-isogenic line Pet33-10. Compared with wild type, the
      expression of BnSmD1 in the early floral buds of apetalous mutant Apet33-10 was
      significantly reduced. Taken together, our results suggest that BnSmD1 may play
      an important role in early floral petal development in B. napus.

PMID- 18065391
TI  - [The influence of virtual reality both on biology experiment and teaching].
AB  - Based on the characters of virtual laboratory of biology and bioinformation, this
      article suggested that the development of the technique would lead to great
      influence and reform on both the experiments of biology and its teaching.
      Furthermore, the technique had an important impact on the traditional studies in
      Biology and its thinking model of students.

PMID- 18065392
TI  - [Application of enzyme-labeled probe in testing of transgenic plant].
AB  - Used alkaline-phosphatase-labeled DNA as a probe to examine the expression of
      foreign UidA gene in transgenic plants. Alkaline phosphatase coupled with
      polyethyleneimine (PEI) using P-benzoquine as the cross-linking reagent was
      covalently linked to single-stranded DNA via glutraldehyde. Such DNA-enzyme
      complexes were used as a probe for dot hybridization and Southern blot. After
      hybridization and incubation with a substrate solution, results can be observed
      directly in three to six hours and the results showed that it was a sensitive,
      specific, rapid, safe and economical probe. Dot hybridization analysis showed
      that the UidA gene was transformed into the target plants and southern blot
      showed that there were at least 5 copies of UidA gene in transgenic plants.

PMID- 18065393
TI  - Cancer-derived lysophosphatidic acid stimulates differentiation of human
      mesenchymal stem cells to myofibroblast-like cells.
AB  - Lysophosphatidic acid (LPA) is enriched in ascites of ovarian cancer patients and
      is involved in growth and invasion of ovarian cancer cells. Accumulating evidence
      suggests cancer-associated myofibroblasts play a pivotal role in tumorigenesis
      through secreting stromal cell-derived factor-1 (SDF-1). In the present study, we
      demonstrate that LPA induces expression of alpha-smooth muscle actin (alpha-SMA),
      a marker for myofibroblasts, in human adipose tissue-derived mesenchymal stem
      cells (hADSCs). The LPA-induced expression of alpha-SMA was completely abrogated
      by pretreatment of the cells with Ki16425, an antagonist of LPA receptors, or by
      silencing LPA(1) or LPA(2) isoform expression with small interference RNA
      (siRNA). LPA elicited phosphorylation of Smad2/3, and siRNA-mediated depletion of
      endogenous Smad2/3 or adenoviral expression of Smad7, an inhibitory Smad,
      abrogated the LPA induced expression of alpha-SMA and phosphorylation of Smad2/3.
      LPA-induced secretion of transforming growth factor (TGF)-beta1 in hADSCs, and
      pretreatment of the cells with SB431542, a TGF-beta type I receptor kinase
      inhibitor, or anti-TGF-beta1 neutralizing antibody inhibited the LPA-induced
      expression of alpha-SMA and phosphorylation of Smad2. Furthermore, ascites from
      ovarian cancer patients or conditioned medium from ovarian cancer cells induced
      expression of alpha-SMA and phosphorylation of Smad2, and pretreatment of the
      cells with Ki16425 or SB431542 abrogated the expression of alpha-SMA and
      phosphorylation of Smad2. In addition, LPA increased the expression of SDF-1 in
      hADSCs, and pretreatment of the cells with Ki16425 or SB431562 attenuated the LPA
      stimulated expression of SDF-1. These results suggest that cancer-derived LPA
      stimulates differentiation of hADSCs to myofibroblast-like cells and increases
      SDF-1 expression through activating autocrine TGF-beta1-Smad signaling pathway.

PMID- 18065394
TI  - Adipose-derived stem cells are a source for cell therapy of the corneal stroma.
AB  - Most corneal diseases affect corneal stroma and include immune or infectious
      diseases, ecstatic disorders, traumatic scars, and corneal dystrophies. Cell
      based therapy is a promising therapeutic approach to overcome the current
      disadvantages of corneal transplantation. We intended to search for a cell source
      to repopulate and regenerate corneal stroma. We investigated the ability of human
      processed lipoaspirate derived (PLA) cells to regenerate corneal stroma in
      experimental animals. In the first set of experiments, we tested the biosafety
      and immunogenicity of human PLA stem cells transplanted into the corneal stroma
      of rabbits. No immune response was elicited even though we used immune-competent
      animals. PLA cells survived up to 10 weeks post-transplant, maintained their
      shape, and remained intermingled in the stroma without disrupting its
      histological pattern. Interestingly, transparency was preserved even 10 weeks
      after the transplant, when PLA cells formed a discontinuous layer in the stroma.
      In the second set of experiments, regeneration of the corneal stroma by PLA cells
      was assessed, creating a niche by partial ablation of the stroma. After 12 weeks,
      human cells were disposed following a multilayered pattern and differentiated
      into functional keratocytes, as assessed by the expression of aldehyde-3
      dehydrogenase and cornea-specific proteoglycan keratocan. Based on our results,
      we believe that adipose-derived adult stem cells can be a cell source for stromal
      regeneration and repopulation in diseased corneas. The low health impact of the
      surgical procedure performed to obtain the PLA cells provides this cell source
      with an additional beneficial feature for its possible future autologous use in
      human patients.

PMID- 18065395
TI  - Derivation, characterization, and in vitro differentiation of canine embryonic
      stem cells.
AB  - Canine embryonic stem (cES) cell lines were generated to establish a large-animal
      preclinical model for testing the safety and efficacy of embryonic stem (ES) cell
      derived tissue replacement therapy. Putative cES cell lines were initiated from
      canine blastocysts harvested from natural matings. Times of harvest were
      estimated as 12-16 days after the presumed surge in circulating levels of
      luteinizing hormone. Four lines established from blastocysts harvested at days 13
      14 postsurge satisfied most of the criteria for embryonic stem cells, whereas
      lines established after day 14 did not. One line, Fred Hutchinson dog (FHDO)-7,
      has been maintained through 34 passages and is presented here. FHDO-7 cells are
      alkaline phosphatase-positive and express both message and protein for the Oct4
      transcription factor. They also express message for Nanog and telomerase but do
      not express message for Cdx2, which is associated with trophectoderm.
      Furthermore, they express a cluster of pluripotency-associated microRNAs (miRs)
      (miR-302b, miR-302c, and miR-367) characteristic of human and mouse ES cells. The
      FHDO-7 cells grow on feeder layers of modified mouse embryonic fibroblasts as
      flat colonies that resemble ES cells from mink, a close phylogenetic relative of
      dog. When cultured in nonadherent plates without feeders, the cells form embryoid
      bodies (EBs). Under various culture conditions, the EBs give rise to ectoderm
      derived neuronal cells expressing gamma-enolase and beta 3-tubulin; mesoderm
      derived cells producing collagen IIA1, cartilage, and bone; and endoderm-derived
      cells expressing alpha-fetoprotein or Clara cell-specific protein.

PMID- 18065396
TI  - Pluripotential reprogramming of the somatic genome in hybrid cells occurs with
      the first cell cycle.
AB  - The fusion of pluripotent embryonic cells with somatic cells results in
      reprogramming of the somatic cell genome. Oct4-green fluorescent protein (GFP)
      transgenes that do not contain the proximal enhancer (PE) region are widely used
      to visualize reprogramming of the somatic to the pluripotent cell state. The
      temporal onset of Oct4-GFP activation has been found to occur 40-48 hours
      postfusion. We asked whether activation of the transgene actually reflects
      activation of the endogenous Oct4 gene. In the current study, we show that
      activation of an Oct4-GFP transgene that contains the PE region occurs within 22
      hours of fusion. In addition, demethylation of the Oct4-GFP transgene and that of
      the endogenous Oct4 and Nanog genes was found to occur within 24 hours of fusion.
      As this timing corresponds with the timing of cell cycle completion in embryonic
      stem cells and fusion hybrids (approximately 22 hours), we postulate that
      pluripotential reprogramming of the somatic cell genome begins during the first
      cell cycle after the fusion of a somatic cell with a pluripotent cell and has
      been completed by day 2 postfusion.

PMID- 18065397
TI  - Wharton's jelly-derived cells are a primitive stromal cell population.
AB  - Here, the literature was reviewed to evaluate whether a population of mesenchymal
      stromal cells derived from Wharton's jelly cells (WJCs) is a primitive stromal
      population. A clear case can be made for WJCs as a stromal population since they
      display the characteristics of MSCs as defined by the International Society for
      Cellular Therapy; for example, they grow as adherent cells with mesenchymal
      morphology, they are self-renewing, they express cell surface markers displayed
      by MSCs, and they may be differentiated into bone, cartilage, adipose, muscle,
      and neural cells. Like other stromal cells, WJCs support the expansion of other
      stem cells, such as hematopoietic stem cells, are well-tolerated by the immune
      system, and they have the ability to home to tumors. In contrast to bone marrow
      MSCs, WJCs have greater expansion capability, faster growth in vitro, and may
      synthesize different cytokines. WJCs are therapeutic in several different pre
      clinical animal models of human disease such as neurodegenerative disease,
      cancer, heart disease, etc. The preclinical work suggests that the WJCs are
      therapeutic via trophic rescue and immune modulation. In summary, WJCs meet the
      definition of MSCs. Since WJCs expand faster and to a greater extent than adult
      derived MSCs, these findings suggest that WJCs are a primitive stromal cell
      population with therapeutic potential. Further work is needed to determine
      whether WJCs engraft long-term and display self-renewal and multipotency in vivo
      and, as such, demonstrate whether Wharton's jelly cells are a true stem cell
      population.

PMID- 18065399
TI  - Characteristics of rain penetration through a gravity ventilator used for natural
      ventilation.
AB  - Gravity ventilators rely simply on air buoyancy to extract air and are widely
      used to exhaust air contaminants and heat from workplaces using minimal energy.
      They are designed to maximize the exhaust flow rate, but the rain penetration
      sometimes causes malfunctioning. In this study, the characteristics of rain
      penetration through a ventilator were examined as a preliminary study to develop
      a ventilator with the maximum exhaust capacity while minimizing rain penetration.
      A model ventilator was built and exposed to artificial rain and wind. The paths,
      intensities and amounts of penetration through the ventilator were observed and
      measured in qualitative and quantitative fashions. In the first phase, the
      pathways and intensities of rain penetration were visually observed. In the
      second phase, the amounts of rain penetration were quantitatively measured under
      the different configurations of ventilator components that were installed based
      on the information obtained in the first-phase experiment. The effects of wind
      speed, grill direction, rain drainage width, outer wall height, neck height and
      leaning angle of the outer wall from the vertical position were analyzed. Wind
      speed significantly affected rain penetration. Under the low crosswind
      conditions, the rain penetration intensities were under the limit of detection.
      Under the high crosswind conditions, grill direction and neck height were the
      most significant factors in reducing rain penetration. The installation of rain
      drainage was also important in reducing rain penetration. The experimental
      results suggest that, with proper configurations of its components, a gravity
      ventilator can be used for natural ventilation without significant rain
      penetration problems.

PMID- 18065398
TI  - Activin alters the kinetics of endoderm induction in embryonic stem cells
      cultured on collagen gels.
AB  - Embryonic stem cell-derived endoderm is critical for the development of cellular
      therapies for the treatment of disease such as diabetes, liver cirrhosis, or
      pulmonary emphysema. Here, we describe a novel approach to induce endoderm from
      mouse embryonic stem (mES) cells using fibronectin-coated collagen gels. This
      technique results in a homogeneous endoderm-like cell population, demonstrating
      endoderm-specific gene and protein expression, which remains committed following
      in vivo transplantation. In this system, activin, normally an endoderm inducer,
      caused an 80% decrease in the Foxa2-positive endoderm fraction, whereas
      follistatin increased the Foxa2-positive endoderm fraction to 78%. Our work
      suggests that activin delays the induction of endoderm through its transient
      precursors, the epiblast and mesendoderm. Long-term differentiation displays a
      twofold reduction in hepatic gene expression and threefold reduction in hepatic
      protein expression of activin-treated cells compared with follistatin-treated
      cells. Moreover, subcutaneous transplantation of activin-treated cells in a
      syngeneic mouse generated a heterogeneous teratoma-like mass, suggesting that
      these were a more primitive population. In contrast, follistatin-treated cells
      resulted in an encapsulated epithelial-like mass, suggesting that these cells
      remained committed to the endoderm lineage. In conclusion, we demonstrate a novel
      technique to induce the direct differentiation of endoderm from mES cells without
      cell sorting. In addition, our work suggests a new role for activin in induction
      of the precursors to endoderm and a new endoderm-enrichment technique using
      follistatin.

PMID- 18065400
TI  - Epidemiological diagnosis of occupational fatigue in a fly-in fly-out operation
      of the mineral industry.
AB  - OBJECTIVE: A prospective epidemiological study was conducted at a fly-in-fly-out
      mining operation in Australia to assess the dynamics of occupational fatigue and
      its potential risk factors. METHODS: Performance and perceived fatigue were
      measured at the start/finish of each 12-h shift throughout the 28-day roster (10
      days day shift work on-site, 5 days rest off-site, 8 days night shift work on
      site and 5 days rest off-site) using the Mackworth Clock Vigilance test and the
      Swedish Occupational Fatigue Inventory, respectively. Additionally, major
      predisposing/reinforcing factors of fatigue were measured including a detailed
      sleep diary (length/quality of sleep, wake patterns), a diary on alcohol
      consumption and a general health/fitness questionnaire. RESULTS: Of 55 production
      staff at the site 52 (95%) participated in the study. Significantly increased
      occupational fatigue was observed at concerning levels at the finish of night
      shifts 1-3 and from day shift 8 onwards. At the measured level, total hours of
      sleep (average 6.8 h per night) and number of standard drinks (average 1.5) were
      not significantly correlated with fatigue measurements. CONCLUSIONS: A disturbed
      diurnal rhythm at the beginning of night shift and a roster of more than eight
      consecutive days were identified as the primary contributing factors to
      occupational fatigue in this setting. The observed magnitude of effects suggests
      adverse implications for safety as the effects on performance were beyond what
      would be expected at blood alcohol concentrations of 0.05%. The results of this
      study have been used to generate highly specific strategies to reduce fatigue in
      the workplace.

PMID- 18065401
TI  - Helicoverpa zea CYP6B8 and CYP321A1: different molecular solutions to the problem
      of metabolizing plant toxins and insecticides.
AB  - Under continual exposure to naturally occurring plant toxins and synthetic
      insecticides, insects have evolved cytochrome P450 monooxygenases (P450s) capable
      of metabolizing a wide range of structurally different compounds. Two such P450s,
      CYP6B8 and CYP321A1, expressed in Helicoverpa zea (a lepidopteran) in response to
      plant allelochemicals and plant signaling molecules metabolize these compounds
      with varying efficiencies. While sequence alignments of these proteins indicate
      highly divergent substrate recognition sites (SRSs), homology models developed
      for them indicate that the two active site cavities have essentially the same
      volume with distinct shapes dictated by side-chain differences in SRS1 and SRS5.
      CYP6B8 has a narrower active site cavity extending from substrate access channel
      pw2a with a very narrow access to the ferryl oxygen atom. This predicted shape
      suggests that bulkier molecules bind further from the ferryl oxygen at positions
      that are not as effectively metabolized. In contrast, CYP321A1 is predicted to
      have a more spacious cavity allowing larger molecules to access the heme-bound
      oxygen. The metabolic profiles for several plant toxins (xanthotoxin, angelicin)
      and insecticides (cypermethrin, aldrin and diazinon) correlate well with these
      predictive models. The absence of Thr in the I helix of CYP321A1 and hydroxyl
      groups on many of its substrates suggests that this insect P450 mediates oxygen
      activation by a mechanism different from that employed by CYP107A1 and CYP158A1,
      which are two bacterial P450s also lacking Thr in their I helix, and most other
      P450s that contain Thr in their I helix.

PMID- 18065402
TI  - Risk of thyroid cancer after exposure to fertility drugs: results from a large
      Danish cohort study.
AB  - BACKGROUND: Findings from the few epidemiological studies that have investigated
      thyroid cancer risk after fertility drugs have been inconclusive. Using data from
      the largest cohort of infertile women to date, we examined the effects of
      fertility drugs on thyroid cancer risk. METHODS: A cohort of 54 362 women with
      infertility problems referred to Danish fertility clinics in the period 1963-1998
      was established. A detailed data collection including information about type and
      amount of treatment was conducted. Using case-cohort techniques, we calculated
      rate ratios (RRs) of thyroid cancer associated with different fertility drugs
      after adjustment for age at first live birth. RESULTS: A total of 29 thyroid
      cancers were identified during follow-up through 2000. Use of clomiphene [RR =
      2.28; 95% confidence interval (CI): 1.08-4.82] or progesterone (RR = 10.14; 95%
      CI: 1.93-53.33) was associated with an increased thyroid cancer risk, although
      the latter estimate was based on few cases. When stratifying for parity status,
      the risk was primarily associated with clomiphene (RR = 3.09; 95% CI: 1.21-7.88)
      in parous women. No significantly increased risk was found after use of
      gonadotrophins, hCG or GnRH. We observed no association with number of cycles of
      use or years since first use (latency). CONCLUSIONS: Clomiphene and possibly
      progesterone may increase thyroid cancer risk, particularly among parous women.
      Longer follow-up is needed to confirm our findings.

PMID- 18065403
TI  - ISG20L2, a novel vertebrate nucleolar exoribonuclease involved in ribosome
      biogenesis.
AB  - Proteomics analyses of human nucleoli provided molecular bases for an
      understanding of the multiple functions fulfilled by these nuclear domains.
      However, the biological roles of about 100 of the identified proteins are
      unpredictable. The present study describes the functional characterization of one
      of these proteins, ISG20L2. We demonstrate that ISG20L2 is a 3' to 5'
      exoribonuclease involved in ribosome biogenesis at the level of 5.8 S rRNA
      maturation, more specifically in the processing of the 12 S precursor rRNA. The
      use of truncated forms of ISG20L2 demonstrated that its N-terminal half promotes
      the nucleolar localization and suggested that its C-terminal half bears the
      exoribonuclease activity. Identification of the binding partners of ISG20L2
      confirmed its involvement in the biogenesis of the large ribosomal subunit. These
      results strongly support the notion that, in human, as it was demonstrated in
      yeast, 5.8 S rRNA maturation requires several proteins in addition to the exosome
      complex. Furthermore this observation greatly sustains the idea that the
      extremely conserved need for correctly processed rRNAs in vertebrates and yeast
      is achieved by close but different mechanisms.

PMID- 18065404
TI  - Non-Hodgkin's lymphoma in very elderly patients over 80 years. A descriptive
      analysis of clinical presentation and outcome.
AB  - BACKGROUND: Non-Hodgkin's lymphoma (NHL) in patients older than 80 years is not a
      rare disease and treatment strategies are often difficult because of associated
      comorbidities. PATIENTS AND METHODS: We entered 205 NHL patients older than 80
      years treated in a single institution in a retrospective analysis to describe
      clinical presentation and outcome and to identify specific prognostic factors.
      RESULTS: The median age was 83 years, and 91% of the cases were B-cell lymphomas
      consisting mainly of diffuse large B-cell lymphoma and marginal zone lymphoma.
      Among patients presenting comorbidities (87%), Charlson index was low in almost
      half of the patients (43%). Patients did not receive any treatment or received
      corticosteroids alone in 15%, surgery, radiotherapy, or monochemotherapy in 35%,
      polychemotherapy without anthracycline in 18%, and anthracycline based in 32%.
      Median overall survival was of 2.2 years. Main reason for death was disease
      progression (57%). Independent prognostic factors of survival were poor
      performance status (P < 10(-4)) and high lactate dehydrogenase level (P < 10(
      5)). Comorbidities were not found to influence survival. CONCLUSIONS: Very
      elderly NHL patients showed similar features and prognostic factors than younger
      patients. Death was related mainly to the disease, meaning that these patients
      should be more frequently treated with standard treatments.

PMID- 18065405
TI  - p53 status correlates with histopathological response in patients with soft
      tissue sarcomas treated using isolated limb perfusion with TNF-alpha and
      melphalan.
AB  - BACKGROUND: Recombinant tumor necrosis factor-alpha (TNF-alpha) combined to
      melphalan is clinically administered through isolated limb perfusion (ILP) for
      regionally advanced soft tissue sarcomas of the limbs. In preclinical studies,
      wild-type p53 gene is involved in the regulation of cytotoxic action of TNF-alpha
      and loss of p53 function contributes to the resistance of tumour cells to TNF
      alpha. The relationship between p53 status and response to TNF-alpha and
      melphalan in patients undergoing ILP is unknown. PATIENTS AND METHODS: We studied
      110 cases of unresectable limbs sarcomas treated by ILP. Immunohistochemistry was
      carried out using DO7mAb, which reacts with an antigenic determinant from the N
      terminal region of both the wild-type and mutant forms of the p53 protein, and
      PAb1620mAb, which reacts with the 1620 epitope characteristic of the wild-type
      native conformation of the p53 protein. The immunohistochemistry data were then
      correlated with various clinical parameters. RESULTS: P53DO7 was found expressed
      at high levels in 28 patients, whereas PAb1620 was negative in 20. The tumours
      with poor histological response to ILP with TNF-alpha and melphalan showed
      significantly higher levels of p53-mutated protein. CONCLUSIONS: Our results
      might be a clue to a role of p53 protein status in TNF-alpha and melphalan
      response in clinical use.

PMID- 18065407
TI  - Dose-escalated CHOEP for the treatment of young patients with aggressive non
      Hodgkin's lymphoma: II. Results of the randomized high-CHOEP trial of the German
      High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL).
AB  - BACKGROUND: The addition of etoposide to combination chemotherapy with
      cyclophosphamide, doxorubicin, vincristine and prednisone [etoposide to
      combination chemotherapy with cyclophosphamide, vincristine and prednisone
      (CHOEP)] improved outcome of young patients with good-prognosis aggressive
      lymphoma. To improve results further, the maximal dose-escalated version of CHOEP
      21 tolerable without stem-cell support (high CHOEP: cyclophosphamide 1400 mg/m2,
      doxorubicin 65 mg/m2, vincristine 2 mg, etoposide 175 mg/m2 x3, prednisone 100 mg
      x5) was compared with CHOEP-21. PATIENTS AND METHODS: Intention-to-treat analysis
      of 389 young (18-60 years) patients with good-prognosis (age-adjusted
      International Prognostic Index = 0, 1) aggressive lymphoma randomized to CHOEP-21
      (n = 194) or high CHOEP (n = 195). RESULTS: There was no difference in 3-year
      event-free (64% versus 67%; P = 0.734) or overall survival (83% versus 87%; P =
      0.849). Neither low-risk nor low-intermediate risk patients benefited from high
      CHOEP. High CHOEP was more toxic than CHOEP-21 (grades 3 and 4 leukocytopenia
      100% versus 87.2%, P < 0.001; thrombocytopenia 80.8% versus 9.6%, P < 0.001;
      infections 35% versus 11%, P < 0.001; therapy-associated deaths 3.1% versus 0%, P
      = 0.03). CONCLUSION: Dose-escalated CHOEP-21 does not provide clinical benefit
      for young patients with good-prognosis aggressive lymphomas. Since differences
      between chemotherapy regimens are compressed by the addition of rituximab, the
      results of this trial have bearing on strategies aiming to improve outcome of
      good-prognosis aggressive lymphomas in the rituximab era.

PMID- 18065406
TI  - Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine
      plus celecoxib or placebo in the first-line treatment of patients with metastatic
      colorectal cancer. EORTC study 40015.
AB  - BACKGROUND: The study aimed to demonstrate the noninferiority of capecitabine to
      5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival
      (PFS) after first-line treatment of metastatic colorectal cancer and the benefit
      of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with
      placebo (P). PATIENTS AND METHODS: Patients were randomly assigned to receive
      FOLFIRI: irinotecan (180 mg/m(2) i.v. on days 1, 15 and 22); FA (200 mg/m(2) i.v.
      on days 1, 2, 15, 16, 29 and 30); 5-FU (400 mg/m(2) i.v. bolus, then 22-h, 600
      mg/m(2) infusion) or CAPIRI: irinotecan (250 mg/m(2) i.v. infusion on days 1 and
      22); capecitabine p.o. (1000 mg/m(2) b.i.d. on days 1-15 and 22-36). Patients
      were additionally randomly assigned to receive either placebo or celecoxib (800
      mg: 2 x 200 mg b.i.d.). RESULTS: The trial was closed following eight deaths
      unrelated to disease progression in the 85 enrolled (629 planned) patients.
      Response rates were 22% for CAPIRI + C, 48% for CAPIRI + P, 32% for FOLFIRI + C
      and 46% for FOLFIRI + P. Median PFS and overall survival (OS) times were shorter
      for CAPIRI versus FOLFIRI (PFS 5.9 versus 9.6 months and OS 14.8 versus 19.9
      months) and celecoxib versus placebo (PFS 6.9 versus 7.8 months and OS 18.3
      versus 19.9 months). CONCLUSION: Due to the small sample size following early
      termination, no definitive conclusions can be drawn in relation to the
      noninferiority of CAPIRI compared with FOLFIRI.

PMID- 18065408
TI  - Nadir CA-125 concentration in the normal range as an independent prognostic
      factor for optimally treated advanced epithelial ovarian cancer.
AB  - BACKGROUND: The amount of residual disease after surgery is considered the most
      important factor influencing the survival of patients with advanced epithelial
      ovarian cancer (adEOC). In optimally treated patients with adEOC, there are no
      well-established prognostic factors [excluding International Federation of
      Gynecology and Obstetrics (FIGO) stage]. The aim of this retrospective study is
      to analyze the prognostic value of the CA-125 nadir after the completion of an
      optimal primary treatment. PATIENTS AND METHODS: Patients treated for adEOC were
      identified from January 1998 to December 2006. INCLUSION CRITERIA: elevated CA
      125 at time of diagnosis (>35 kU/l); FIGO stage III-IV treated with optimal
      primary treatment (residual tumor <1 cm and carboplatin/taxane-based combination
      chemotherapy); and complete response to optimal primary treatment with
      normalization of CA-125. RESULTS: Patients, n = 96: 44 group A (< or =10 kU/l);
      52 group B (11-35 kU/l). Median progression-free survival (PFS) was 42 and 20
      months for groups A and B, respectively (P = 0.0087). Median overall survival
      (OS) was 84 and 43 months for groups A and B, respectively (P < 0.0001). The Cox
      model showed a highly significant impact on PFS and OS in relation to CA-125
      nadir levels. CONCLUSIONS: The CA-125 nadir value is a strong independent
      prognostic factor for optimally treated adEOC after achieving a complete
      response.

PMID- 18065409
TI  - Cost-effectiveness of HER2 testing and 1-year adjuvant trastuzumab therapy for
      early breast cancer.
AB  - BACKGROUND: Clinical studies have demonstrated statistically significant
      reduction of breast cancer relapse and improved overall survival by adding
      trastuzumab for 1 year after adjuvant chemotherapy in human epidermal growth
      factor receptor-2 protein (HER2)/neu-positive breast cancer. The aim of this
      study was to analyze the cost-effectiveness of HER2/neu testing and the addition
      of 1-year adjuvant trastuzumab after adjuvant chemotherapy from a societal
      perspective in a Swedish setting. MATERIAL AND METHODS: We used a Markov state
      transition model to simulate HER2/neu testing and adjuvant trastuzumab treatment
      in a hypothetical cohort of early breast cancer patients. RESULTS: The cost per
      quality adjusted life year (QALY) gained for immunohistochemical (IHC) testing
      for all patients with FISH confirmation of IHC 2+ and 3+ and 1-year adjuvant
      trastuzumab for FISH-positive patients was estimated to 36,000 euros. The
      strategy of FISH testing for all patients, with 1-year adjuvant trastuzumab for
      FISH-positive patients was associated with the longest quality adjusted survival
      of all evaluated treatment strategies and the cost per QALY gained was estimated
      to 41,500 euros. The remaining testing and treatment strategies were dominated.
      CONCLUSION: FISH testing for all patients with 1-year adjuvant trastuzumab for
      FISH+ patients is a cost-effective treatment option from a societal perspective.

PMID- 18065410
TI  - Plasmid-mediated AmpC beta-lactamases in Enterobacteriaceae lacking inducible
      chromosomal ampC genes: prevalence at a Swiss university hospital and occurrence
      of the different molecular types in Switzerland.

PMID- 18065411
TI  - Bloodstream infections caused by multidrug-resistant Klebsiella pneumoniae
      producing the carbapenem-hydrolysing VIM-1 metallo-beta-lactamase: first Italian
      outbreak.
AB  - OBJECTIVES: To investigate the first Italian outbreak of bloodstream infections
      caused by multidrug-resistant (MDR) Klebsiella pneumoniae producing metallo-beta
      lactamase (MBL), which occurred in three wards of one large tertiary-care
      hospital in Genoa, Italy, from September 2004 to March 2005. METHODS: MBL
      production was screened by an imipenem-EDTA disc synergy test and confirmed by a
      conventional hydrolysis test. Antibiotic susceptibility was determined by broth
      microdilution or disc diffusion. PFGE was used to study the genetic relatedness
      of isolates. PCR and sequencing were carried out to identify the beta-lactamase
      genes and to analyse the genetic context of the MBL gene. Outer membrane protein
      (OMP) profiles were analysed by SDS-PAGE. RESULTS: Nine cases of bloodstream
      infections caused by an MDR strain of K. pneumoniae producing the VIM-1 MBL and
      the SHV-5 extended-spectrum beta-lactamase (ESBL) were identified. The isolates
      exhibited various carbapenem resistance levels (imipenem MICs ranged from 4 to 64
      mg/L) and were resistant to other beta-lactams, fluoroquinolones,
      trimethoprim/sulfamethoxazole and chloramphenicol. The isolate with the highest
      imipenem MIC also lacked the k36 OMP. The bla(VIM-1) gene cassette was part of
      the variable region of a class 1 integron that also included an aac(6')-IIc
      cassette. The ESBL and MBL genes were transferable by conjugation. CONCLUSIONS:
      This is the first report on the emergence of an MDR strain of K. pneumoniae
      producing the VIM-1 MBL, causing an outbreak of bloodstream infections in an
      Italian hospital. The strain evolved through OMP alterations generating a mutant
      with increased carbapenem resistance.

PMID- 18065412
TI  - Identifying barriers to the rapid administration of appropriate antibiotics in
      community-acquired pneumonia.
AB  - BACKGROUND: Despite multiple guidelines for management of community-acquired
      pneumonia (CAP), barriers to guideline use are rarely evaluated. METHODS: We
      performed quantitative and qualitative surveys of junior doctors before
      implementation of a CAP management pathway. After implementation, we identified
      patient-related determinants of pathway adherence by multivariate analysis.
      RESULTS: We surveyed 83 (77%) of the 108 junior doctors working in acute medicine
      between August 2001 and July 2002 and selected 8 for in-depth interview. We
      identified five main themes that influence pathway adherence. First, education
      (recognized to be insufficient on antimicrobial therapy) and experience:
      increasing clinical experience was associated with greater knowledge of pathway
      content, but decreasing likelihood of consulting the pathway. Second, attitudes
      to CAP: doctors recognized that they had not treated CAP with respect early on.
      Third, work intensity and lack of senior support were barriers to good practice.
      Fourth, guideline factors: they need to be simple enough to be easy to use while
      containing enough information to be useful. Fifth, CAP is sometimes difficult to
      diagnose on admission. Notably, when given three clinical scenarios only six (7%)
      of respondents assessed CAP severity correctly. In the intervention study, early
      administration of antibiotics was associated (P < 0.05) with indicators of
      increased severity of illness (pulse, respiratory rate, oxygenation and
      temperature) in addition to being admitted to the intervention hospital (P <
      0.001). CONCLUSIONS: Some of the identified barriers could be overcome by
      undergraduate and postgraduate education. However, equally important are
      organizational barriers that can only be overcome by systems redesign.

PMID- 18065413
TI  - Tissue concentrations: do we ever learn?
AB  - Over the last decades, numerous papers have appeared--and still are appearing-
      that describe concentrations in tissues in an effort to predict the efficacy of
      an antimicrobial agent based on these concentrations and MICs for microorganisms.
      A common method is to use measurements of concentrations in tissue homogenates,
      comparing these with values derived from the corresponding blood samples and on
      that basis draw conclusions with respect to the potential clinical use of the
      drug. This approach is not justifiable for a number of reasons that includes both
      pharmacokinetic as well as pharmacodynamic causes. This way of presenting data
      with the derived conclusions is often misleading and may ultimately be harmful in
      patient care.

PMID- 18065414
TI  - Endoplasmic reticulum stress increases the expression of
      methylenetetrahydrofolate reductase through the IRE1 transducer.
AB  - Methylenetetrahydrofolate reductase (MTHFR), an enzyme in folate and homocysteine
      metabolism, influences many cellular processes including methionine and
      nucleotide synthesis, methylation reactions, and maintenance of homocysteine at
      nontoxic levels. Mild deficiency of MTHFR is common in many populations and
      modifies risk for several complex traits including vascular disease, birth
      defects, and cancer. We recently demonstrated that MTHFR can be up-regulated by
      NF-kappaB, an important mediator of cell survival that is activated by
      endoplasmic reticulum (ER) stress. This observation, coupled with the reports
      that homocysteine can induce ER stress, prompted us to examine the possible
      regulation of MTHFR by ER stress. We found that several well characterized stress
      inducers (tunicamycin, thapsigargin, and A23187) as well as homocysteine could
      increase Mthfr mRNA and protein in Neuro-2a cells. The induction of MTHFR was
      also observed after overexpression of inositol-requiring enzyme-1 (IRE1) and was
      inhibited by a dominant-negative mutant of IRE1. Because IRE1 triggers c-Jun
      signaling, we examined the possible involvement of c-Jun in up-regulation of
      MTHFR. Transfection of c-Jun and two activators of c-Jun (LiCl and sodium
      valproate) increased MTHFR expression, whereas a reported inhibitor of c-Jun
      (SP600125) and a dominant-negative derivative of c-Jun N-terminal kinase-1
      reduced MTHFR activation. We conclude that ER stress increases MTHFR expression
      and that IRE1 and c-Jun mediate this activation. These findings provide a novel
      mechanism by which the ER can regulate homeostasis and allude to an important
      role for MTHFR in cell survival.

PMID- 18065415
TI  - Genome-wide H3K9 histone acetylation profiles are altered in benzopyrene-treated
      MCF7 breast cancer cells.
AB  - Current toxicogenomic approaches generate transcriptional profiles that can
      identify functional gene expression signatures of environmental toxicants.
      However, the intricate processes governing transcription are overlaid with a
      complex set of molecular instructions involving epigenetic modifications. These
      commands regulate both gene expression and chromatin organization through
      coordinated sets of histone modifications and heritable DNA methylation patterns.
      Although the effects of specific environmental toxicants on gene expression are
      the subject of much study, the epigenetic effects of such compounds are poorly
      understood. Here we have used human promoter tiling arrays along with chromatin
      immunoprecipitation to identify changes in histone acetylation profiles because
      of chemical exposure. Chromatin from cells exposed to the polyaromatic
      hydrocarbon benzo(a)pyrene was immunoprecipitated with antibodies against
      acetylated histones. Affymetrix promoter tiling microarrays were probed to
      generate epigenomic profiles of hypo- and hyperacetylated chromatin localized to
      gene promoter regions. Statistical analyses, data mining, and expression studies
      revealed that treated cells possessed differentially acetylated gene promoter
      regions and gene-specific expression changes. This chromatin immunoprecipitation
      on-chip approach permits genome-wide profiling of histone acetylation patterns
      that can identify chromatin-related signatures of environmental toxicants and
      potentially determine the molecular pathways these changes target. This approach
      also has potential applications for profiling histone modifications and DNA
      methylation changes during embryonic development, in cancer biology, and in the
      development and assessment of cancer therapeutics.

PMID- 18065416
TI  - Identification of novel direct Stat3 target genes for control of growth and
      differentiation.
AB  - Signal transducer and activator of transcription 3 (Stat3) is a key regulator of
      gene expression in response to signaling of the glycoprotein 130 (gp130) family
      cytokines, including interleukin 6, oncostatin M, and leukemia inhibitory factor.
      Many efforts have been made to identify Stat3 target genes and to understand the
      mechanism of how Stat3 regulates gene expression. Using the microarray technique,
      hundreds of genes have been documented to be potential Stat3 target genes in
      different cell types. However, only a small fraction of these genes have been
      proven to be true direct Stat3 target genes. Here we report the identification of
      novel direct Stat3 target genes using a genome-wide screening procedure based on
      the chromatin immunoprecipitation method. These novel Stat3 target genes are
      involved in a diverse array of biological processes such as oncogenesis, cell
      growth, and differentiation. We show that Stat3 can act as both a repressor and
      activator on its direct target genes. We further show that most of the novel
      Stat3 direct target genes are dependent on Stat3 for their transcriptional
      regulation. In addition, using a physiological cell system, we demonstrate that
      Stat3 is required for the transcriptional regulation of two of the newly
      identified direct Stat3 target genes important for muscle differentiation.

PMID- 18065417
TI  - Translational efficiency of a non-AUG initiation codon is significantly affected
      by its sequence context in yeast.
AB  - Previous studies have shown that translation of mrna for yeast glycyl-tRNA
      synthetase is alternatively initiated from UUG and a downstream AUG initiation
      codon. Evidence presented here shows that unlike an AUG initiation codon,
      efficiency of this non-AUG initiation codon is significantly affected by its
      sequence context, in particular the nucleotides at positions -3 to -1 relative to
      the initiation codon. A/A/R (R represents A Or G) and C/G/C appear to be the most
      and least favorable sequences at these positions, respectively. Mutation of the
      native context sequence -3 to -1 from AAA to CGC reduced translation initiation
      from the UUG codon up to 32-fold and resulted in loss of mitochondrial
      respiration. although an AUG initiation codon is, in general, unresponsive to
      context changes in yeast, an AAA (-3 to -1) to CGC mutation still reduced its
      initiating activity up to 8-fold under similar conditions. these results suggest
      that sequence context is more important for translation initiation in yeast than
      previously appreciated.

PMID- 18065418
TI  - Inactivation of the calcium sensing receptor inhibits E-cadherin-mediated cell
      cell adhesion and calcium-induced differentiation in human epidermal
      keratinocytes.
AB  - Extracellular Ca(2+) (Ca(2+)(o)) is a critical regulator that promotes
      differentiation in epidermal keratinocytes. The calcium sensing receptor (CaR) is
      essential for mediating Ca(2+) signaling during Ca(2+)(o)-induced
      differentiation. Inactivation of the endogenous CaR-encoding gene CASR by
      adenoviral expression of a CaR antisense cDNA inhibited the Ca(2+)(o)-induced
      increase in intracellular free calcium (Ca(2+)(i)) and expression of terminal
      differentiation genes, while promoting apoptosis. Ca(2+)(o) also instigates E
      cadherin-mediated cell-cell adhesion, which plays a critical role in
      orchestrating cellular signals mediating cell survival and differentiation.
      Raising Ca(2+)(o) concentration ([Ca(2+)](o)) from 0.03 to 2 mm rapidly induced
      the co-localization of alpha-, beta-, and p120-catenin with E-cadherin in the
      intercellular adherens junctions (AJs). To assess whether CaR is required for the
      Ca(2+)(o)-induced activation of E-cadherin signaling, we examined the impact of
      CaR inactivation on AJ formation. Decreased CaR expression suppressed the
      Ca(2+)(o)-induced AJ formation, membrane translocation, and the complex formation
      of E-cadherin, catenins, and the phosphatidylinositol 3-kinase (PI3K), although
      the expression of these proteins was not affected. The assembly of the E-cadherin
      catenin-PI3K complex was sensitive to the pharmacologic inhibition of Src family
      tyrosine kinases but was not affected by inhibition of Ca(2+)(o)-induced rise in
      Ca(2+)(i). Inhibition of CaR expression blocked the Ca(2+)(o)-induced tyrosine
      phosphorylation of beta-, gamma-, and p120-catenin, PI3K, and the tyrosine kinase
      Fyn and the association of Fyn with E-cadherin and PI3K. Our results indicate
      that the CaR regulates cell survival and Ca(2+)(o)-induced differentiation in
      keratinocytes at least in part by activating the E-cadherin/PI3K pathway through
      a Src family tyrosine kinase-mediated signaling.

PMID- 18065419
TI  - Mechanism of regulation of group IVA phospholipase A2 activity by Ser727
      phosphorylation.
AB  - Although group IVA cytosolic phospholipase A(2) (cPLA(2)alpha) has been reported
      to be phosphorylated at multiple Ser residues, the mechanisms by which
      phosphorylation at different sites regulates cPLA(2)alpha activities are not
      fully understood. To explore the possibility that phosphorylation of Ser(727)
      modulates cellular protein-protein interactions, we measured the effect of
      Ser(727) mutations on the interaction of cPLA(2)alpha with a reported
      cPLA(2)alpha-binding protein, p11. In vitro activity assays and membrane binding
      measurements by surface plasmon resonance analysis showed that a heterotetramer
      (A2t) of p11 and annexin A2, but not p11 or annexin A2 alone, directly binds
      cPLA(2)alpha via Ser(727), which keeps the enzyme from binding the membrane and
      catalyzing the phospholipid hydrolysis. Phosphorylation of Ser(727) disrupts this
      inhibitory cPLA(2)alpha-A2t interaction, thereby activating cPLA(2)alpha.
      Subcellular translocation and activity measurements in HEK293 cells cotransfected
      with cPLA(2)alpha and p11 also showed that p11, in the form of A2t, inhibits
      cPLA(2)alpha by the same mechanism and that phosphorylation of Ser(727) activates
      cPLA(2)alpha by interfering with the inhibitory cPLA(2)alpha-A2t interaction.
      Collectively, these studies provide new insight into the regulatory mechanism of
      cPLA(2)alpha through Ser(727) phosphorylation.

PMID- 18065421
TI  - Reactive oxygen species modulate Anopheles gambiae immunity against bacteria and
      Plasmodium.
AB  - The involvement of reactive oxygen species (ROS) in mosquito immunity against
      bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae.
      Strains of An. gambiae with higher systemic levels of ROS survive a bacterial
      challenge better, whereas reduction of ROS by dietary administration of
      antioxidants significantly decreases survival, indicating that ROS are required
      to mount effective antibacterial responses. Expression of several ROS
      detoxification enzymes increases in the midgut and fat body after a blood meal.
      Furthermore, expression of several of these enzymes increases to even higher
      levels when mosquitoes are fed a Plasmodium berghei-infected meal, indicating
      that the oxidative stress after a blood meal is exacerbated by Plasmodium
      infection. Paradoxically, a complete lack of induction of catalase mRNA and lower
      catalase activity were observed in P. berghei-infected midguts. This suppression
      of midgut catalase expression is a specific response to ookinete midgut invasion
      and is expected to lead to higher local levels of hydrogen peroxide. Further
      reduction of catalase expression by double-stranded RNA-mediated gene silencing
      promoted parasite clearance by a lytic mechanism and reduced infection
      significantly. High mosquito mortality is often observed after P. berghei
      infection. Death appears to result in part from excess production of ROS, as
      mortality can be decreased by oral administration of uric acid, a strong
      antioxidant. We conclude that ROS modulate An. gambiae immunity and that the
      mosquito response to P. berghei involves a local reduction of detoxification of
      hydrogen peroxide in the midgut that contributes to limit Plasmodium infection
      through a lytic mechanism.

PMID- 18065420
TI  - Domain architecture and biochemical characterization of vertebrate Mcm10.
AB  - Mcm10 plays a key role in initiation and elongation of eukaryotic chromosomal DNA
      replication. As a first step to better understand the structure and function of
      vertebrate Mcm10, we have determined the structural architecture of Xenopus
      laevis Mcm10 (xMcm10) and characterized each domain biochemically. Limited
      proteolytic digestion of the full-length protein revealed N-terminal-, internal
      (ID)-, and C-terminal (CTD)-structured domains. Analytical ultracentrifugation
      revealed that xMcm10 self-associates and that the N-terminal domain forms
      homodimeric assemblies. DNA binding activity of xMcm10 was mapped to the ID and
      CTD, each of which binds to single- and double-stranded DNA with low micromolar
      affinity. The structural integrity of xMcm10-ID and CTD is dependent on the
      presence of bound zinc, which was experimentally verified by atomic absorption
      spectroscopy and proteolysis protection assays. The ID and CTD also bind
      independently to the N-terminal 323 residues of the p180 subunit of DNA
      polymerase alpha-primase. We propose that the modularity of the protein
      architecture, with discrete domains for dimerization and for binding to DNA and
      DNA polymerase alpha-primase, provides an effective means for coordinating the
      biochemical activities of Mcm10 within the replisome.

PMID- 18065422
TI  - The model plant Medicago truncatula exhibits biparental plastid inheritance.
AB  - The plastid, which originated from the endosymbiosis of a cyanobacterium,
      contains its own plastid DNA (ptDNA) that exhibits a unique mode of inheritance.
      Approximately 80% of angiosperms show maternal inheritance, whereas the remainder
      exhibit biparental inheritance of ptDNA. Here we studied ptDNA inheritance in the
      model legume, Medicago truncatula. Cytological analysis of mature pollen with DNA
      specific fluorescent dyes suggested that M. truncatula is one of the few model
      plants potentially showing biparental inheritance of ptDNA. We further examined
      pollen by electron microscopy and revealed that the generative cell (a mother of
      sperm cells) indeed has many DNA-containing plastids. To confirm biparental
      inheritance genetically, we crossed two ecotypes (Jemalong A17 and A20), and the
      transmission mode of ptDNA was investigated by a PCR-assisted polymorphism.
      Consistent with the cytological observations, the majority of F(1) plants
      possessed ptDNAs from both parents. Interestingly, cotyledons of F(1) plants
      tended to retain a biparental ptDNA population, while later emergent leaves
      tended to be uniparental with either one of the parental plastid genotypes.
      Biparental transmission was obvious in the F(2) population, in which all plants
      showed homoplasmy with either a paternal or a maternal plastid genotype.
      Collectively, these data demonstrated that M. truncatula is biparental for ptDNA
      transmission and thus can be an excellent model to study plastid genetics in
      angiosperms.

PMID- 18065423
TI  - Paradoxical embolism with an intact interatrial septum.

PMID- 18065424
TI  - Early decrease of oxidative stress by atorvastatin in hypercholesterolaemic
      patients: effect on circulating vitamin E.
AB  - AIMS: Statins inhibit oxidative stress, but the interplay between cholesterol
      lowering and antioxidant vitamins is still unclear. Aims of the study were to
      assess if statins inhibit oxidative stress independently from cholesterol
      lowering, to assess the behaviour of vitamin E simultaneously with the changes of
      oxidative stress, to determine in vitro if atorvastatin was able to directly
      influence platelet-mediated LDL oxidation and vitamin E consumption. METHODS AND
      RESULTS: In 30 hypercholesterolaemic patients (HC) and 20 healthy subjects (HS),
      urinary isoprostanes and plasma vitamin E were determined. The HC were randomized
      to diet or diet plus atorvastatin 10 mg/day. Compared with HS, HC had higher
      isoprostanes and lower vitamin E levels. The statin-allocated group showed a
      reduction of isoprostanes after only 3 days (-18.8%, P < 0.01); after 30 days, a
      stronger reduction of isoprostanes was noted (-37.1%, P < 0.01) whereas an
      increase of vitamin E (+42%, P < 0.01) and a reduction of cholesterol (-24.9%, P
      < 0.01) were observed. The diet-allocated group showed a weak decrease of
      cholesterol after 30 days. In vitro study showed that atorvastatin dose
      dependently inhibited platelet-mediated LDL oxidation and isoprostane formation
      with a mechanism involving NADPH-oxidase. CONCLUSION: The study provides the
      first evidence that atorvastatin exerts an early antioxidant effect that could
      contribute to enhancing circulating vitamin E.

PMID- 18065425
TI  - Sixty-four slice computed tomography for the diagnosis of multiple intra-thoracic
      metallic bodies.

PMID- 18065426
TI  - TFBS identification based on genetic algorithm with combined representations and
      adaptive post-processing.
AB  - MOTIVATION: Identification of transcription factor binding sites (TFBSs) plays an
      important role in deciphering the mechanisms of gene regulation. Recently, GAME,
      a Genetic Algorithm (GA)-based approach with iterative post-processing, has shown
      superior performance in TFBS identification. However, the basic GA in GAME is not
      elaborately designed, and may be trapped in local optima in real problems. The
      feature operators are only applied in the post-processing, but the final
      performance heavily depends on the GA output. Hence, both effectiveness and
      efficiency of the overall algorithm can be improved by introducing more advanced
      representations and novel operators in the GA, as well as designing the post
      processing in an adaptive way. RESULTS: We propose a novel framework GALF-P,
      consisting of Genetic Algorithm with Local Filtering (GALF) and adaptive post
      processing techniques (-P), to achieve both effectiveness and efficiency for TFBS
      identification. GALF combines the position-led and consensus-led representations
      used separately in current GAs and employs a novel local filtering operator to
      get rid of false positives within an individual efficiently during the
      evolutionary process in the GA. Pre-selection is used to maintain diversity and
      avoid local optima. Post-processing with adaptive adding and removing is
      developed to handle general cases with arbitrary numbers of instances per
      sequence. GALF-P shows superior performance to GAME, MEME, BioProspector and
      BioOptimizer on synthetic datasets with difficult scenarios and real test
      datasets. GALF-P is also more robust and reliable when further compared with
      GAME, the current state-of-the-art approach. AVAILABILITY:
      http://www.cse.cuhk.edu.hk/~tmchan/GALFP/.

PMID- 18065427
TI  - TimeClust: a clustering tool for gene expression time series.
AB  - TimeClust is a user-friendly software package to cluster genes according to their
      temporal expression profiles. It can be conveniently used to analyze data
      obtained from DNA microarray time-course experiments. It implements two original
      algorithms specifically designed for clustering short time series together with
      hierarchical clustering and self-organizing maps. AVAILABILITY: TimeClust
      executable files for Windows and LINUX platforms can be downloaded free of charge
      for non-profit institutions from the following web site:
      http://aimed11.unipv.it/TimeClust.

PMID- 18065428
TI  - ConoServer, a database for conopeptide sequences and structures.
AB  - SUMMARY: ConoServer is a new database dedicated to conopeptides, a large family
      of peptides found in the venom of marine snails of the genus Conus. These
      peptides have an exceptional diversity of sequences and chemical modifications
      and their ability to block ion channels makes them important as drug leads and
      tools for physiological studies. ConoServer uses standardized names and a genetic
      and structural classification scheme to present data retrieved from SwissProt,
      GenBank, the Protein DataBank and the literature. The ConoServer web site
      incorporates specialized features like the graphic display of post-translational
      modifications that are extensively present in conopeptides. Currently, ConoServer
      manages 1214 nucleic sequences (from 54 Conus species), 2258 proteic sequences
      (from 66 Conus species) and 99 3D structures. AVAILABILITY:
      http://research1t.imb.uq.edu.au/conoserver/.

PMID- 18065430
TI  - Whither development and developmental biology?

PMID- 18065429
TI  - Co-evolving residues in membrane proteins.
AB  - MOTIVATION: The analysis of co-evolving residues has been exhaustively evaluated
      for the prediction of intramolecular amino acid contacts in soluble proteins.
      Although a variety of different methods for the detection of these co-evolving
      residues have been developed, the fraction of correctly predicted contacts
      remained insufficient for their reliable application in the construction of
      structural models. Membrane proteins, which constitute between one-fourth and one
      third of all proteins in an organism, were only considered in few individual case
      studies. RESULTS: We present the first general study of correlated mutations in
      alpha-helical membrane proteins. Using seven different prediction algorithms, we
      extracted co-evolving residues for 14 membrane proteins having a solved 3D
      structure. On average, distances between correlated pairs of residues lying on
      different transmembrane segments were found to be significantly smaller compared
      to a random prediction. Covariation of residues was frequently found in direct
      sequence neighborhood to helix-helix contacts. Based on the results obtained from
      individual prediction methods, we constructed a consensus prediction for every
      protein in the dataset that combines obtained correlations from different
      prediction algorithms and simultaneously removes likely false positives. Using
      this consensus prediction, 53% of all predicted residue pairs were found within
      one helix turn of an observed helix-helix contact. Based on the combination of co
      evolving residues detected with the four best prediction algorithms, interacting
      helices could be predicted with a specificity of 83% and sensitivity of 42%.
      AVAILABILITY: http://webclu.bio.wzw.tum.de/helixcorr/

PMID- 18065431
TI  - Insertional mutagenesis by the Tol2 transposon-mediated enhancer trap approach
      generated mutations in two developmental genes: tcf7 and synembryn-like.
AB  - Gene trap and enhancer trap methods using transposon or retrovirus have been
      recently described in zebrafish. However, insertional mutants using these methods
      have not been reported. We report here development of an enhancer trap method by
      using the Tol2 transposable element and identification and characterization of
      insertional mutants. We created 73 fish lines that carried single copy insertions
      of an enhancer trap construct, which contained the zebrafish hsp70 promoter and
      the GFP gene, in their genome and expressed GFP in specific cells, tissues and
      organs, indicating that the hsp70 promoter is highly capable of responding to
      chromosomal enhancers. First, we analyzed genomic DNA surrounding these
      insertions. Fifty-one of them were mapped onto the current version of the genomic
      sequence and 43% (22/51) were located within transcribed regions, either exons or
      introns. Then, we crossed heterozygous fish carrying the same insertions and
      identified two insertions that caused recessive mutant phenotypes. One disrupted
      the tcf7 gene, which encodes a transcription factor of the Tcf/Lef family
      mediating Wnt signaling, and caused shorter and wavy median fin folds and
      pectoral fins. We knocked down Lef1, another member of the Tcf/Lef family also
      expressed in the fin bud, in the tcf7 mutant, and revealed functional redundancy
      of these factors and their essential role in establishment of the apical
      ectodermal ridge (AER). The other disrupted the synembryn-like gene (synbl), a
      homolog of the C. elegans synembryn gene, and caused embryonic lethality and
      small pigment spots. The pigment phenotype was rescued by application of
      forskolin, an activator of adenylyl cyclase, suggesting that the synbl gene
      activates the Galpha(S) pathway leading to activation of adenylyl cyclase. We
      thus demonstrated that the transposon-mediated enhancer trap approach can indeed
      create insertional mutations in developmental genes. Our present study provides a
      basis for the development of efficient transposon-mediated insertional
      mutagenesis in a vertebrate.

PMID- 18065432
TI  - Hoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of
      lumbar motoneurons.
AB  - A central question in neural development is how the broad diversity of neurons is
      generated in the vertebrate CNS. We have investigated the function of Hoxc10 and
      Hoxd10 in mouse lumbar motoneuron development. We show that Hoxc10 and Hoxd10 are
      initially expressed in most newly generated lumbar motoneurons, but subsequently
      become restricted to the lateral division of the lateral motor column (lLMC).
      Disruption of Hoxc10 and Hoxd10 caused severe hindlimb locomotor defects.
      Motoneurons in rostral lumbar segments were found to adopt the phenotype of
      thoracic motoneurons. More caudally the lLMC and dorsal-projecting axons were
      missing, yet most hindlimb muscles were innervated. The loss of the lLMC was not
      due to decreased production of motoneuron precursors or increased apoptosis.
      Instead, presumptive lLMC neurons failed to migrate to their normal position, and
      did not differentiate into other motoneurons or interneurons. Together, these
      results show that Hoxc10 and Hoxd10 play key roles in establishing lumbar
      motoneuron columnar, divisional and motor pool identity.

PMID- 18065433
TI  - The HUPO proteomics standards initiative--easing communication and minimizing
      data loss in a changing world.
AB  - The amount of data currently being generated by proteomics laboratories around
      the world is increasing exponentially, making it ever more critical that
      scientists are able to exchange, compare and retrieve datasets when re-evaluation
      of their original conclusions becomes important. Only a fraction of this data is
      published in the literature and important information is being lost every day as
      data formats become obsolete. The Human Proteome Organisation Proteomics
      Standards Initiative (HUPO-PSI) was tasked with the creation of data standards
      and interchange formats to allow both the exchange and storage of such data
      irrespective of the hardware and software from which it was generated. This
      article will provide an update on the work of this group, the creation and
      implementation of these standards and the standards-compliant data repositories
      being established as result of their efforts.

PMID- 18065434
TI  - Induced abortion in Denmark: effect of socio-economic situation and country of
      birth.
AB  - BACKGROUND: Equal access to health care is considered a key in Scandinavian
      healthcare policy. However, problematic differences between the socio-economic
      situation of immigrants and that of native Scandinavians are increasingly
      challenging this aspect of the Scandinavian welfare model. The present study
      focuses on how socio-economic characteristics and country of birth are associated
      with induced abortion. METHODS: A structured questionnaire was used to collect
      information among 1351 women requesting abortion and a control group of 1306
      women intending birth. RESULTS: The strongest factor associated with the decision
      to have an abortion was being single (OR 39.1; 23.8-64.2), followed by being aged
      19 years or below (OR 29.6; 13.4-65.5), having two children or more (OR 7.05;
      5.29-9.39) and being unskilled (OR 2.48; 1.49-4.10), student (OR 2.29; 1.52-3.43)
      or unemployed (OR 1.65; 1.11-2.46). When evaluating the effect of social exposure
      on abortion among Danish-born and foreign-born women, the higher rate of abortion
      among non-Westerners was found to be caused by the composition of non-Westerners
      more often being unemployed, having a low income and having two or more children
      rather than the fact that they are coming from a non-Western country. CONCLUSION:
      Immigrant women comprise a vulnerable group, with a poor socio-economic status.
      This situation exposes immigrant women to increased risk of induced abortion. In
      a society with an increasing heterogeneous population, the vulnerable situation
      of immigrant women has to be addressed, if equal access to health care is to be
      maintained.

PMID- 18065435
TI  - Acute renal failure in patients with severe sepsis and septic shock--a
      significant independent risk factor for mortality: results from the German
      Prevalence Study.
AB  - BACKGROUND: Sound data about the prevalence of acute renal failure (ARF) among
      patients with severe sepsis and septic shock are lacking. Further, it is not
      known whether ARF is an independent risk factor for mortality in septic patients
      or merely an indicator of disease severity. METHODS: A prospective cross
      sectional one-day prevalence study was carried out in a representative sample of
      German ICUs, divided into five strata (< 200 beds; 201-400 beds; 401-600 beds; >
      600 beds; university hospitals). 3877 patients were screened of whom 415 had
      severe sepsis and septic shock. RESULTS: Fourteen patients (3.4%) had chronic
      dialysis-dependent RF and were excluded from analysis. Of the remaining 401
      patients, 166 (41.4%) had ARF, as defined by a rise in creatinine above twice the
      upper limit of normal and/or a drop in urine output to < 0.5 ml/kg bodyweight.
      Median APACHE II score was 22 in patients with ARF and 16 in patients without ARF
      (p< 0.0001). Patients with severe sepsis/septic shock had an overall hospital
      mortality of 55.2%. Hospital mortality in patients with ARF was 67.3% and without
      ARF 42.8% (p< 0.0001). After adjustment for APACHE II score and age, ARF remained
      a significant independent risk factor for death [odds ratio (OR) 2.11, 95%
      confidence interval (CI) 1.27-3.52]. Mortality in septic patients was not
      associated with pre-existing, non-dialysis-dependent chronic kidney disease,
      whereas in dialysis-dependent patients with sepsis mortality increased to 86%.
      CONCLUSION: In this representative survey in patients with severe sepsis/septic
      shock, prevalence of ARF is high with 41.4%. ARF represents a significant
      independent risk factor for mortality in these patients.

PMID- 18065437
TI  - Delayed priming promotes CNS regeneration post-rhizotomy in Neurocan and Brevican
      deficient mice.
AB  - A wealth of literature has provided evidence that reactive tissue at the site of
      CNS injury is rich in chondroitin sulfate proteoglycans which may contribute to
      the non-permissive nature of the CNS. We have recently demonstrated using a
      murine model of human brachial plexus injury that the chondroitin sulfate
      proteoglycans Neurocan and Brevican are differentially expressed by two subsets
      of astrocytes in the spinal cord dorsal root entry zone (DREZ) following dorsal
      root lesion (Beggah et al., Neuroscience 133: 749-762, 2005). However, direct
      evidence for a growth-inhibitory role of these proteoglycans in vivo is still
      lacking. We therefore performed dorsal root lesion (rhizotomy) in mice deficient
      in both Neurocan and Brevican. Rhizotomy in these animals resulted in no
      significant increase in the number of sensory fibres regenerating through the
      DREZ compared to genetically matched controls. Likewise, a conditioning
      peripheral nerve lesion prior to rhizotomy, which increases the intrinsic growth
      capacity of sensory neurons, enhanced growth to the same extent in transgenic and
      control mice, indicating that absence of these proteoglycans alone is not
      sufficient to further promote entry into the spinal cord. In contrast, when
      priming of the median nerve was performed at a clinically relevant time, i.e. 7
      weeks post-rhizotomy, the growth of a subpopulation of sensory axons across the
      DREZ was facilitated in Neurocan/Brevican-deficient, but not in control animals.
      This demonstrates for the first time that (i) Neurocan and/or Brevican contribute
      to the non-permissive environment of the DREZ several weeks after lesion and that
      (ii) delayed stimulation of the growth program of sensory neurons can facilitate
      regeneration across the DREZ provided its growth-inhibitory properties are
      attenuated. Post-injury enhancement of the intrinsic growth capacity of sensory
      neurons combined with removal of inhibitory chondroitin sulfate proteoglycans may
      therefore help to restore sensory function and thus attenuate the chronic pain
      resulting from human brachial plexus injury.

PMID- 18065436
TI  - The tauopathy associated with mutation +3 in intron 10 of Tau: characterization
      of the MSTD family.
AB  - Multiple system tauopathy with presenile dementia (MSTD) is an inherited disease
      caused by a (g) to (a) transition at position +3 in intron 10 of Tau. It belongs
      to the spectrum of frontotemporal dementia and parkinsonism linked to chromosome
      17 with mutations in Tau (FTDP-17T). Here we present the longitudinal clinical,
      neuropsychological, neuroimaging, neuropathological, biochemical and genetic
      characterization of the MSTD family. Presenting signs were consistent with the
      behavioural variant of frontotemporal dementia in 17 of 21 patients. Two
      individuals presented with an atypical form of progressive supranuclear palsy and
      two others with either severe postural imbalance or an isolated short-term memory
      deficit. Memory impairment was present at the onset in 15 patients, with word
      finding difficulties and stereotyped speech also being common. Parkinsonism was
      first noted 3 years after the onset of symptoms. Neuroimaging showed the most
      extensive grey matter loss in the hippocampus, parahippocampal gyrus and frontal
      operculum/insular cortex of the right hemisphere and, to a lesser extent, in the
      anterior cingulate gyrus, head of the caudate nucleus and the posterolateral
      orbitofrontal cortex and insular cortex bilaterally. Neuropathologically,
      progressive nerve cell loss, gliosis and coexistent neuronal and/or glial
      deposits consisting mostly of 4-repeat tau were present in frontal, cingulate,
      temporal and insular cortices, white matter, hippocampus, parahippocampus, basal
      ganglia, selected brainstem nuclei and spinal cord. Tau haplotyping indicated
      that specific haplotypes of the wild-type allele may act as modifiers of disease
      presentation. Quantitative neuroimaging has been used to analyse the progression
      of atrophy in affected individuals and for predicting disease onset in an
      asymptomatic mutation carrier. This multidisciplinary study provides a
      comprehensive description of the natural history of disease in one of the largest
      known families with FTDP-17T.

PMID- 18065438
TI  - Neural correlates of cognitive inflexibility during task-switching in obsessive
      compulsive disorder.
AB  - A deficit in cognitive flexibility is acknowledged as a cognitive trait for
      obsessive-compulsive disorder (OCD). However, no investigations to date have used
      a cognitive activation paradigm to specify the neural correlates of this deficit
      in OCD. The objective of this study was to clarify how abnormal brain activities
      relate to cognitive inflexibility in OCD, using a task-switching paradigm. A task
      switching paradigm which has two kinds of task-set was applied to 21 patients
      with OCD and 21 healthy subjects of matching age, IQ and sex, during an event
      related functional magnetic resonance imaging experiment. Compared with the
      healthy subjects, patients with OCD exhibited a significantly higher error rate
      in task-switch trials (P < 0.05). Healthy controls showed significant activation
      in various areas, including dorsal frontal-striatal regions, during task
      switching, whereas patients with OCD showed no activation in these areas.
      Significant differences were also observed in the dorsal frontal-striatal regions
      and ventromedial prefrontal and right orbitofrontal cortexes between patients
      with OCD and healthy controls. Correlation analysis indicated that the
      activations of orbitofrontal cortex were related with the performance in both
      groups and also with the activation of anterior cingulate cortex in the OCD
      group. These findings replicate previous studies of cognitive inflexibility in
      OCD and provide neural correlates related to a task-switching deficit in OCD. The
      results suggest that impaired task-switching ability in OCD patients might be
      associated with an imbalance in brain activation between dorsal and ventral
      frontal-striatal circuits.

PMID- 18065440
TI  - MRI study of the size, symmetry and function of the trunk muscles among elite
      cricketers with and without low back pain.
AB  - OBJECTIVES: To determine if asymmetry of trunk muscles and deficits of motor
      control exist among elite cricketers with and without low back pain (LBP).
      DESIGN: Single-blinded observational quasi-experimental design study SETTING:
      Assessments were conducted in a hospital setting. PARTICIPANTS: Among a total
      eligible sample of 26 male elite cricketers (mean age 21.2 (SD 2.0) years),
      selected to attend a national training camp, 21 participated in the study. RISK
      FACTORS: The independent variables were 'group' (LBP or asymptomatic) and
      'cricket position' (fast bowler versus the rest of the squad). MAIN OUTCOME
      MEASUREMENTS: The dependent variables were the cross-sectional areas (CSA) of the
      quadratus lumborum (QL), lumbar erector spinae plus multifidus (LES + M) and
      psoas muscles, the thickness of the internal oblique (IO) and transversus
      abdominis (TrA) muscles, and the amount of lateral slide of the anterior
      abdominal fascia. RESULTS: The QL and LES + M muscles were larger ipsilateral to
      the dominant arm. In the subgroup of fast bowlers with LBP, the asymmetry in the
      QL muscle was the greatest. The IO muscle was larger on the side contralateral to
      the dominant arm. No difference between sides was found for the psoas and TrA
      muscles. Cricketers with LBP showed a reduced ability to draw in the abdominal
      wall and contract the TrA muscle independently of the other abdominal muscles.
      CONCLUSIONS: This study provides new insights into trunk muscle size and function
      in elite cricketers, and evidence of impaired motor control in elite cricketers
      with LBP. Rehabilitation using a motor control approach has been shown to be
      effective for subjects with LBP, and this may also benefit elite cricketers.

PMID- 18065439
TI  - Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia,
      ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of
      mtDNA maintenance.
AB  - Mutations in nuclear genes involved in mitochondrial DNA (mtDNA) maintenance
      cause a wide range of clinical phenotypes associated with the secondary
      accumulation of multiple mtDNA deletions in affected tissues. The majority of
      families with autosomal dominant progressive external ophthalmoplegia (PEO)
      harbour mutations in genes encoding one of three well-characterized proteins--pol
      gamma, Twinkle or Ant 1. Here we show that a heterozygous mis-sense mutation in
      OPA1 leads to multiple mtDNA deletions in skeletal muscle and a mosaic defect of
      cytochrome c oxidase (COX). The disorder presented with visual failure and optic
      atrophy in childhood, followed by PEO, ataxia, deafness and a sensory-motor
      neuropathy in adult life. COX-deficient skeletal muscle fibres contained supra
      threshold levels of multiple mtDNA deletions, and genetic linkage, sequencing and
      expression analysis excluded POLG1, PEO1 and SLC25A4, the gene encoding Ant 1, as
      the cause. This demonstrates the importance of OPA1 in mtDNA maintenance, and
      implicates OPA1 in diseases associated with secondary defects of mtDNA.

PMID- 18065441
TI  - Influence of repetitive open sea dives and physical exercises on right-to-left
      shunting in healthy divers.
AB  - OBJECTIVE: Paradoxical gas embolism through right-to-left (R/L) shunts is
      considered as a potential cause of certain types of decompression sickness. AIM:
      To assess whether 4 months of repetitive diving and strenuous exercises would
      lead to an increased prevalence of R/L shunting in a group of military divers.
      METHODS: Using a standardised contrast-enhanced transcranial Doppler technique,
      17 divers were re-examined for the presence of a R/L shunt 4 months after their
      initial examinations. R/L shunts were classified as type I if observed only after
      a straining manoeuvre, and type II if present at rest. RESULTS: Initial
      prevalence of R/L shunt was 41%: six type I shunts and one type II. At the second
      examination, prevalence was 47%, with the appearance of one type I shunt that was
      not previously present. We found no significant increase in the prevalence and
      size of R/L shunts. CONCLUSION: It is speculated that diving-related phenomena,
      such as variations in right atrial pressures during the end stages of or events
      immediately after a dive could generate an R/L shunt. However, extreme conditions
      of repetitive diving and strenuous exercises do not cause permanent modification
      in R/L permeability over a period of 4 months.

PMID- 18065442
TI  - Workload demands in professional multi-stage cycling races of varying duration.
AB  - OBJECTIVE: To analyse and compare the workload exerted by professional cyclists
      in 5-day, 8-day and 21-day stage races (5-SR, 8-SR, 21-SR). METHODS: The study
      subjects were 30 professional cyclists competing in 10 5-SR, 5 8-SR and 5 21-SR.
      Heart rate (HR) was measured during the races and categorised into three
      intensity zones: Z1 (below the ventilatory threshold (VT)), Z2 (between VT and
      the respiratory compensation threshold (RCT)) and Z3 (above RCT). The training
      impulse (TRIMP) was calculated by multiplying the sum of the time spent in each
      zone by 1, 2 and 3, respectively. Monotony (average TRIMP/SD) and strain (total
      TRIMPxmonotony) were also calculated for each race type. RESULTS: The average
      time spent in Z3 during each stage was significantly (p<0.05) higher for 5-SR (
      approximately 31 min) and 8-SR ( approximately 28 min) than for 21-SR (
      approximately 14 min). Daily TRIMP values in 5-SR ( approximately 400) and 8-SR (
      approximately 395) were also higher than in 21-SR ( approximately 370). Monotony
      was similar across races ( approximately 3) but strain was about three times
      higher for 21-SR than for 5-SR and 8-SR. CONCLUSIONS: The cyclists' effort by
      stage was less for 21-SR than for 5-SR and 8-SR. Competition strain and monotony
      accumulated during longer races influence the choice of strategies adopted by
      cyclists. It is likely that the intensity of each stage is modulated by total
      race duration, with longer races averaging the lowest daily workload.

PMID- 18065443
TI  - A prospective cohort study of the incidence of injuries among junior Australian
      football players: evidence for an effect of playing-age level.
AB  - OBJECTIVE: To determine the rate of injury in junior Australian football, and to
      describe the patterns and severity of these injuries across nine levels of play
      (U9 to U18). DESIGN: Prospective cohort study. SETTING: Junior Australian
      football games and training sessions were observed for 54 teams from New South
      Wales and Victoria over the 2004 playing season. PARTICIPANTS: Six teams from
      each level of play were invited to participate in the study. Overall, data were
      collected for 51 teams over 40 208 hours of player exposure. INDEPENDENT
      VARIABLES: Participation and injury data were collected prospectively. MAIN
      OUTCOME MEASURES: Injury was defined as "any trauma that causes some disability
      or pain". Injury severity was identified by the action of players immediately
      after the injury event. RESULTS: The overall injury rate was 18.0 (95% CI 16.6 to
      19.3) injuries per 1000 player hours. The main cause of injury was body contact
      (67.3%). There was an increased frequency of sprains and strains, and injury
      severity with increasing level of play. The rates of injury for players who
      stayed off the field (6.4 injuries per 1000 hours, 95% CI 5.6 to 7.2) or were
      advised to seek off-field medical advice (5.0 injuries per 1000 hours, 95% CI 4.3
      to 5.7) were low. CONCLUSION: Compared with the adult game, junior Australian
      football is relatively safe. However, injury rates increase as children progress
      across age-determined levels of play towards the more adult form of the game.

PMID- 18065444
TI  - The epidemiology of rock-climbing injuries.
AB  - OBJECTIVES: To determine the prevalence and nature of rock-climbing injuries, and
      the factors associated with these injuries. DESIGN: A retrospective cross
      sectional study. SETTING: Rock climbers were recruited at five outdoor and six
      indoor climbing venues in the UK. PARTICIPANTS: 201 active rock climbers (163
      male, 38 female climbers) aged 16-62 years. ASSESSMENT OF RISK FACTORS: Rock
      climbing behaviours and key demographics. MAIN OUTCOME MEASURES: Injuries
      requiring medical attention or withdrawal from participation for > or = 1 day.
      RESULTS: Around 50% of climbers had sustained > or = 1 injury in the past 12
      months, causing a total of 275 distinct anatomical injuries. 21 climbers (10%)
      had sustained acute climbing injuries as a result of a fall, 67 (33%) had chronic
      overuse injuries, and 57 (28%) had acute injuries caused by strenuous climbing
      moves. Dedicated climbers participating in different forms of rock climbing more
      often and at a higher level of technical difficulty may be more prone to injury,
      particularly overuse injuries of the finger and shoulder. The principal sources
      of treatment or advice sought by climbers were physiotherapists (18%), other
      climbers (14%) and doctors (11%). CONCLUSIONS: Climbing frequency and technical
      difficulty are associated with climbing injuries occurring at both indoor and
      outdoor venues, particularly cumulative trauma to the upper extremities.

PMID- 18065445
TI  - Absence of CD36 protects against atherosclerosis in ApoE knock-out mice with no
      additional protection provided by absence of scavenger receptor A I/II.
AB  - AIMS: The role of scavenger receptors in atherogenesis is controversial as a
      result of conflicting reports and a recent hypothesis suggesting that scavenger
      receptor absence would enhance the pro-inflammatory, pro-atherogenic milieu. This
      study addresses the effect of combined absence of scavenger receptors CD36 and
      SRA I/II on atherosclerosis lesion development in the apolipoprotein E knock-out
      (apoE degrees ) model. METHODS: We created background-related strains of apoE
      degrees , scavenger receptor A I/II knock-out (SRA degrees )/apoE degrees , CD36
      knock-out (CD36 degrees )/apoE degrees , and CD36 degrees /SRA degrees /apoE
      degrees mice that were >99% C57Bl/6. Four-week-old mice were fed a Western diet
      for 12 weeks and were assessed for lesion burden/morphology, risk factors for
      atherosclerosis, inflammatory mediators, and macrophage function. RESULTS: There
      was a 61 and 74% decrease in total aortic lesion area in CD36 degrees /apoE
      degrees males and females, respectively, compared with apoE degrees controls. The
      absence of SRA was protective (32% decrease in lesion) in female mice. The
      combined absence of CD36 and SRA provided no further protection in either gender.
      Macrophages from mice lacking CD36 had decreased pro-inflammatory characteristics
      and less migration to a pro-inflammatory stimulus. Plasma levels of
      cytokines/chemokines showed that CD36 degrees /apoE degrees and CD36 degrees /SRA
      degrees /apoE degrees mice had a less pro-inflammatory phenotype compared with
      apoE degrees and SRA degrees /apoE degrees mice. Oblivious mice in the apoE
      degrees background ruled out potential 'passenger gene' effects in the case of
      CD36. CONCLUSION: These results provide new insights into the pro-atherogenic
      mechanisms of CD36 by implicating processes other than modified lipoprotein
      uptake.

PMID- 18065446
TI  - Combination of cardiac conduction disease and long QT syndrome caused by mutation
      T1620K in the cardiac sodium channel.
AB  - AIMS: The aim of the present study was to elucidate the molecular mechanism
      underlying the concomitant occurrence of cardiac conduction disease and long QT
      syndrome (LQT3), two SCN5A channelopathies that are explained by loss-of-function
      and gain-of-function, respectively, in the cardiac Na+ channel. METHODS AND
      RESULTS: A Caucasian family with prolonged QT interval, intermittent bundle
      branch block, sudden cardiac death, and syncope was investigated. Lidocaine (1
      mg/kg i.v.) normalized the prolonged QT interval and rescued bundle-branch block.
      An SCN5A mutation analysis was performed that revealed a C-to-A mutation at
      position 4859 (exon 28), predicted to change a highly conserved threonine for a
      lysine at position 1620. Mutant channels were characterized both in Xenopus
      oocytes and HEK293 cells. The T1620K mutation remarkably altered the properties
      of Nav1.5 channels. In particular, the voltage-dependence of the current decay
      time constants was largely lost. As a consequence, mutant channels inactivated
      faster than wild-type channels at potentials negative to -30 mV, resulting in
      less Na+ inward current (loss-of-function), but significantly slower at
      potentials positive to -30 mV, resulting in an increased Na+ inward current (gain
      of-function). Moreover, we found a hyperpolarized shift of steady-state
      activation and an accelerated recovery from inactivation (gain-of-function). At
      the same time, channel availability was significantly reduced at the resting
      membrane potential (loss-of-function). CONCLUSION: We conclude that lysine at
      position 1620 leads to both loss-of-function and gain-of-function properties in
      hNav1.5 channels, which may consequently cause in the same individuals impaired
      impulse propagation in the conduction system and prolonged QTc intervals,
      respectively.

PMID- 18065447
TI  - Stochastic severing of actin filaments by actin depolymerizing factor/cofilin
      controls the emergence of a steady dynamical regime.
AB  - Actin dynamics (i.e., polymerization/depolymerization) powers a large number of
      cellular processes. However, a great deal remains to be learned to explain the
      rapid actin filament turnover observed in vivo. Here, we developed a minimal
      kinetic model that describes key details of actin filament dynamics in the
      presence of actin depolymerizing factor (ADF)/cofilin. We limited the molecular
      mechanism to 1), the spontaneous growth of filaments by polymerization of actin
      monomers, 2), the ageing of actin subunits in filaments, 3), the cooperative
      binding of ADF/cofilin to actin filament subunits, and 4), filament severing by
      ADF/cofilin. First, from numerical simulations and mathematical analysis, we
      found that the average filament length, L, is controlled by the concentration of
      actin monomers (power law: 5/6) and ADF/cofilin (power law: -2/3). We also showed
      that the average subunit residence time inside the filament, T, depends on the
      actin monomer (power law: -1/6) and ADF/cofilin (power law: -2/3) concentrations.
      In addition, filament length fluctuations are approximately 20% of the average
      filament length. Moreover, ADF/cofilin fragmentation while modulating filament
      length keeps filaments in a high molar ratio of ATP- or ADP-P(i) versus ADP-bound
      subunits. This latter property has a protective effect against a too high
      severing activity of ADF/cofilin. We propose that the activity of ADF/cofilin in
      vivo is under the control of an affinity gradient that builds up dynamically
      along growing actin filaments. Our analysis shows that ADF/cofilin regulation
      maintains actin filaments in a highly dynamical state compatible with the
      cytoskeleton dynamics observed in vivo.

PMID- 18065448
TI  - Subpiconewton dynamic force spectroscopy using magnetic tweezers.
AB  - We introduce a simple method for dynamic force spectroscopy with magnetic
      tweezers. This method allows application of subpiconewton force and twist control
      by calibration of the applied force from the height of the magnets. Initial
      dynamic force spectroscopy experiments on DNA molecules revealed a large
      hysteresis that is caused by viscous drag on the magnetic bead and will conceal
      weak interactions. When smaller beads are used, this hysteresis is sufficiently
      reduced to reveal intramolecular interactions at subpiconewton forces. Compared
      with typical quasistatic force spectroscopy, a significant reduction of
      measurement time is achieved, allowing the real-time study of transient
      structures and reaction intermediates. As a proof of principle, nucleosome
      nucleosome interactions on a subsaturated chromatin fiber were analyzed.

PMID- 18065449
TI  - Biophysical analysis of Thermus aquaticus single-stranded DNA binding protein.
AB  - Due to their involvement in processes such as DNA replication, repair, and
      recombination, bacterial single-stranded DNA binding (SSB) proteins are essential
      for the survival of the bacterial cell. Whereas most bacterial SSB proteins form
      homotetramers in solution, dimeric SSB proteins were recently discovered in the
      Thermus/Deinococcus group. In this work we characterize the biophysical
      properties of the SSB protein from Thermus aquaticus (TaqSSB), which is
      structurally quite similar to the tetrameric SSB protein from Escherichia coli
      (EcoSSB). The binding of TaqSSB and EcoSSB to single-stranded nucleic acids was
      found to be very similar in affinity and kinetics. Mediated by its highly
      conserved C-terminal region, TaqSSB interacts with the chi-subunit of E. coli DNA
      polymerase III with an affinity that is similar to that of EcoSSB. Using
      analytical ultracentrifugation, we show that TaqSSB mutants are able to form
      tetramers in solution via arginine-mediated hydrogen-bond interactions that we
      identified in the crystal packing of wild-type TaqSSB. In EcoSSB, we identified a
      homologous arginine residue involved in the formation of higher aggregates and
      metastable highly cooperative single-stranded DNA binding under low salt
      conditions.

PMID- 18065450
TI  - Conformation of the c-Fos/c-Jun complex in vivo: a combined FRET, FCCS, and MD
      modeling study.
AB  - The activator protein-1 transcription factor is a heterodimer containing one of
      each of the Fos and Jun subfamilies of basic-region leucine-zipper proteins. We
      have previously shown by fluorescence cross-correlation spectroscopy (FCCS) that
      the fluorescent fusion proteins Fos-EGFP and Jun-mRFP1, cotransfected in HeLa
      cells, formed stable complexes in situ. Here we studied the relative position of
      the C-terminal domains via fluorescence resonance energy transfer (FRET) measured
      by flow cytometry and confocal microscopy. To get a more detailed insight into
      the conformation of the C-terminal domains of the complex we constructed C
      terminal labeled full-length and truncated forms of Fos. We developed a novel
      iterative evaluation method to determine accurate FRET efficiencies regardless of
      relative protein expression levels, using a spectral- or intensity-based
      approach. The full-length C-terminal-labeled Jun and Fos proteins displayed a
      FRET-measured average distance of 8 +/- 1 nm. Deletion of the last 164 amino
      acids at the C-terminus of Fos resulted in a distance of 6.1 +/- 1 nm between the
      labels. FCCS shows that Jun-mRFP1 and the truncated Fos-EGFP also interact stably
      in the nucleus, although they bind to nuclear components with lower affinity.
      Thus, the C-terminal end of Fos may play a role in the stabilization of the
      interaction between activator protein-1 and DNA. Molecular dynamics simulations
      predict a dye-to-dye distance of 6.7 +/- 0.1 nm for the dimer between Jun-mRFP1
      and the truncated Fos-EGFP, in good agreement with our FRET data. A wide variety
      of models could be developed for the full-length dimer, with possible dye-to-dye
      distances varying largely between 6 and 20 nm. However, from our FRET results we
      can conclude that more than half of the occurring dye-to-dye distances are
      between 6 and 10 nm.

PMID- 18065451
TI  - Protein diffusion on charged membranes: a dynamic mean-field model describes time
      evolution and lipid reorganization.
AB  - As charged macromolecules adsorb and diffuse on cell membranes in a large variety
      of cell signaling processes, they can attract or repel oppositely charged lipids.
      This results in lateral membrane rearrangement and affects the dynamics of
      protein function. To address such processes quantitatively we introduce a dynamic
      mean-field scheme that allows self-consistent calculations of the equilibrium
      state of membrane-protein complexes after such lateral reorganization of the
      membrane components, and serves to probe kinetic details of the process.
      Applicable to membranes with heterogeneous compositions containing several types
      of lipids, this comprehensive method accounts for mobile salt ions and charged
      macromolecules in three dimensions, as well as for lateral demixing of charged
      and net-neutral lipids in the membrane plane. In our model, the mobility of
      membrane components is governed by the diffusion-like Cahn-Hilliard equation,
      while the local electrochemical potential is based on nonlinear Poisson-Boltzmann
      theory. We illustrate the method by applying it to the adsorption of the anionic
      polypeptide poly-Lysine on negatively charged lipid membranes composed of binary
      mixtures of neutral and monovalent lipids, or onto ternary mixtures of neutral,
      monovalent, and multivalent lipids. Consistent with previous calculations and
      experiments, our results show that at steady-state multivalent lipids (such as
      PIP(2)), but not monovalent lipid (such as phosphatidylserine), will segregate
      near the adsorbing macromolecules. To address the corresponding diffusion of the
      adsorbing protein in the membrane plane, we couple lipid mobility with the
      propagation of the adsorbing protein through a dynamic Monte Carlo scheme. We
      find that due to their higher mobility dictated by the electrochemical potential,
      multivalent lipids such as PIP(2) more quickly segregate near oppositely charged
      proteins than do monovalent lipids, even though their diffusion constants may be
      similar. The segregation, in turn, slows protein diffusion, as lipids introduce
      an effective drag on the motion of the adsorbate. In contrast, monovalent lipids
      such as phosphatidylserine only weakly segregate, and the diffusions of protein
      and lipid remain largely uncorrelated.

PMID- 18065452
TI  - Image correlation spectroscopy of multiphoton images correlates with collagen
      mechanical properties.
AB  - Multiphoton microscopy (MPM) holds promise as a noninvasive imaging technique for
      characterizing collagen structure, and thus mechanical properties, through
      imaging second harmonic generation (SHG) and two-photon fluorescence in
      engineered and real connective tissues. Controlling polymerization pH to
      manipulate collagen gel microstructure, we quantified pore and fiber dimensions
      using both standard methods and image correlation spectroscopy (ICS) on MPM,
      scanning electron, and darkfield microscopy images. The latter two techniques are
      used to confirm microstructural measurements made from MPM images. As
      polymerization pH increased from 5.5 to 8.5, mean fiber diameter decreased from
      3.7 +/- 0.7 microm to 1.6 +/- 0.3 microm, the average pore size decreased from
      81.7 +/- 3.7 microm(2) to 7.8 +/- 0.4 microm(2), and the pore area fraction
      decreased from 56.8% +/- 0.8% to 18.0% +/- 1.3% (measured from SHG images),
      whereas the storage modulus G' and loss modulus G'', components of the shear
      modulus, increased approximately 33-fold and approximately 16-fold, respectively.
      A characteristic length scale measured using ICS, W(ICS), correlates well with
      the mean fiber diameter from SHG images (R(2) = 0.95). Semiflexible network
      theory predicts a scaling relationship of the collagen gel storage modulus (G')
      depending upon mesh size and fiber diameter, which are estimated from SHG images
      using ICS. We conclude that MPM and ICS are an effective combination to assess
      bulk mechanical properties of collagen hydrogels in a noninvasive, objective, and
      systematic fashion and may be useful for specific in vivo applications.

PMID- 18065453
TI  - Dynamic light scattering and optical absorption spectroscopy study of pH and
      temperature stabilities of the extracellular hemoglobin of Glossoscolex
      paulistus.
AB  - The extracellular hemoglobin of Glossoscolex paulistus (HbGp) is constituted of
      subunits containing heme groups, monomers and trimers, and nonheme structures,
      called linkers, and the whole protein has a minimum molecular mass near 3.1 x
      10(6) Da. This and other proteins of the same family are useful model systems for
      developing blood substitutes due to their extracellular nature, large size, and
      resistance to oxidation. HbGp samples were studied by dynamic light scattering
      (DLS). In the pH range 6.0-8.0, HbGp is stable and has a monodisperse size
      distribution with a z-average hydrodynamic diameter (D(h)) of 27 +/- 1 nm. A more
      alkaline pH induced an irreversible dissociation process, resulting in a smaller
      D(h) of 10 +/- 1 nm. The decrease in D(h) suggests a complete hemoglobin
      dissociation. Gel filtration chromatography was used to show unequivocally the
      oligomeric dissociation observed at alkaline pH. At pH 9.0, the dissociation
      kinetics is slow, taking a minimum of 24 h to be completed. Dissociation rate
      constants progressively increase at higher pH, becoming, at pH 10.5, not
      detectable by DLS. Protein temperature stability was also pH-dependent. Melting
      curves for HbGp showed oligomeric dissociation and protein denaturation as a
      function of pH. Dissociation temperatures were lower at higher pH. Kinetic
      studies were also performed using ultraviolet-visible absorption at the Soret
      band. Optical absorption monitors the hemoglobin autoxidation while DLS gives
      information regarding particle size changes in the process of protein
      dissociation. Absorption was analyzed at different pH values in the range 9.0-9.8
      and at two temperatures, 25 degrees C and 38 degrees C. At 25 degrees C, for pH
      9.0 and 9.3, the kinetics monitored by ultraviolet-visible absorption presents a
      monoexponential behavior, whereas for pH 9.6 and 9.8, a biexponential behavior
      was observed, consistent with heme heterogeneity at more alkaline pH. The
      kinetics at 38 degrees C is faster than that at 25 degrees C and is biexponential
      in the whole pH range. DLS dissociation rates are faster than the autoxidation
      dissociation rates at 25 degrees C. Autoxidation and dissociation processes are
      intimately related, so that oligomeric protein dissociation promotes the increase
      of autoxidation rate and vice versa. The effect of dissociation is to change the
      kinetic character of the autoxidation of hemes from monoexponential to
      biexponential, whereas the reverse change is not as effective. This work shows
      that DLS can be used to follow, quantitatively and in real time, the kinetics of
      changes in the oligomerization of biologic complex supramolecular systems. Such
      information is relevant for the development of mimetic systems to be used as
      blood substitutes.

PMID- 18065454
TI  - The dynamics of phosphodiesterase activation in rods and cones.
AB  - Phototransduction starts with the activation of a rhodopsin (respectively,
      coneopsin) molecule, located in the outer segment of rod (respectively, cone)
      photoreceptors. The subsequent amplification pathway proceeds via the G-protein
      transducin to the activation of phosphodiesterase (PDE), a G-protein coupled
      effector enzyme. In this article, we study the dynamics of PDE activation by
      constructing a Markov model that is based on the underlying chemical reactions
      including multiple rhodopsin phosphorylations. We derive explicit equations for
      the mean and the variance of activated PDE. Our analysis reveals that a low
      rhodopsin lifetime variance is neither necessary nor sufficient to achieve
      reliable PDE activation. The numerical simulations show that during the rising
      phase the variability of PDE activation is much lower compared to the recovery
      phase, and this property depends crucially on the transducin activation rates.
      Furthermore, we find that the dynamics of the activation process greatly differs
      depending on whether rhodopsin or PDE deactivation limits the recovery of the
      photoresponse. Finally, our simulations for cones show that only very few PDEs
      are activated by an excited photopigment, which might explain why in S-cones no
      single photon response can be observed.

PMID- 18065455
TI  - Sensitive detection of malaria infection by third harmonic generation imaging.
AB  - Malaria remains a major health concern worldwide, with 350-500 million cases
      reported annually in endemic countries. In this study, we report a novel and
      highly sensitive optical-based detection of malaria-infected blood cells by third
      harmonic generation (THG) imaging of hemozoin pigment that is naturally deposited
      by the parasite during its lifecycle. The THG signal from the hemozoin was
      greater than we have observed in any cell type with signal/noise ratios that
      reach 1000:1. This method allows a rapid and robust detection of early stage
      infections of blood cells. The immense nonlinear response of the intrinsic
      parasitic by-product pigments suggests that automated optical detection by THG
      could be used for sensitive and rapid screening of parasite infection in blood
      samples.

PMID- 18065456
TI  - A chaotic pore model of polypeptide antibiotic action.

PMID- 18065457
TI  - Anisotropy induced by macroscopic boundaries: surface-normal mapping using
      diffusion-weighted imaging.
AB  - In MRI, macroscopic boundaries lead to a diffusion-related increase in signal
      intensity near them--an effect commonly referred to as edge-enhancement. In
      diffusion-weighted imaging protocols where the signal attenuation due to
      diffusion results predominantly from the application of magnetic field gradients,
      edge-enhancement will depend on the orientation of these diffusion gradients. The
      resulting diffusion anisotropy can be exploited to map the direction normal to
      the macroscopic boundary. Simulations suggest that the hypothesized anisotropy
      may be within observable limits even when the voxel contains no boundary itself-
      hence, the name remote-anisotropy. Moreover, for certain experimental parameters
      there may be significant phase cancellations within the voxel that may lead to an
      edge detraction effect. When this is avoided, the eigenvector corresponding to
      the smallest eigenvalue of the diffusion tensor obtained from diffusion-tensor
      imaging can be used to create surface-normal maps conveniently. Experiments
      performed on simple geometric constructs as well as real tissue demonstrate the
      feasibility of using the edge-enhancement mechanism to map orientations
      orthogonal to macroscopic surfaces, which may be used to assess the integrity of
      tissue and organ boundaries noninvasively.

PMID- 18065458
TI  - Pore mutations of the Escherichia coli MscS channel affect desensitization but
      not ionic preference.
AB  - Mechanosensitive channels rescue bacterial cells from a fate of lysis when they
      transfer from a high- to low-osmolarity environment. Of three Escherichia coli
      mechanosensitive proteins studied to date, only MscS-Ec demonstrates a small
      anionic preference and a desensitized, nonconducting state under sustained
      pressure. Little is known about the mechanisms generating these distinctive
      properties. Eliminating the sole positive charge in the MscS-Ec pore region
      (Arg(88)) did not alter anionic preference. Adding positive charges at either end
      of the pore did not augment anionic preference, and placing negative charges
      within the pore did not diminish it. Thus, pore charges do not control this
      characteristic. However, from this analysis we identified mutations in the hinge
      region of the MscS-Ec pore helix (at Gly(113)) that profoundly affected ability
      of the channel to desensitize. Substitution with nonpolar (Ala, Pro) or polar
      (Asp, Arg, Ser) residues inhibited transition to the desensitized state.
      Interestingly, Gly(113) replaced with Met did not impede desensitization. Thus,
      although Gly is not specifically required at position 113, MscS desensitization
      is strongly influenced by the residue situated here. Mutations at residues
      further into the pore also regulated desensitization. Transition to this unique
      mechanosensitive channel state is discussed in terms of existing data.

PMID- 18065459
TI  - Domain nucleation rates and interfacial line tensions in supported bilayers of
      ternary mixtures containing galactosylceramide.
AB  - Domains within the plane of the plasma membrane, referred to as membrane rafts,
      have been a topic of considerable interest in the field of membrane biophysics.
      Although model membrane systems have been used extensively to study lipid phase
      behavior as it relates to the existence of rafts, very little work has focused on
      either the initial stage of lipid domain nucleation, or the relevant physical
      parameters such as temperature and interfacial line tension which control
      nucleation. In this work, we utilize a method in which the kinetic process of
      lipid domain nucleation is imaged by atomic force microscopy and modeled using
      classical theory of nucleation to map interfacial line tension in ternary lipid
      mixtures. These mixtures consist of a fluid phase lipid component (1,2-dilauroyl
      sn-glycero-3-phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, or
      1,2-dioleoyl-sn-glycero-3-phosphocholine), a solid phase component
      (galactosylceramide), and cholesterol. Interfacial line tension measurements of
      galactosylceramide-rich domains track with our previously measured area/perimeter
      ratios and height mismatches measured here. Line tension also follows known
      trends in cholesterol interactions and partitioning, as we observed previously
      with area/perimeter ratios. Our line tension measurements are discussed in
      combination with recent line tension measurements to address line tension
      regulation by cholesterol and the dynamic nature of membrane rafts.

PMID- 18065460
TI  - Mathematical analysis and quantification of fluorescent proteins as
      transcriptional reporters.
AB  - Fluorescent proteins are often used as reporters of transcriptional activity.
      Here we present a mathematical characterization of a novel fluorescent reporter
      that was recently engineered to have a short half-life (approximately 12 min).
      The advantage of this destabilized protein is that it can track the transient
      transcriptional response often exhibited by signaling pathways. Our mathematical
      model takes into account the maturation time and half-life of the fluorescent
      protein. We demonstrate that our characterization allows transient transcript
      profiles to be inferred from fluorescence data. We also investigate a stochastic
      version of the model. Our analysis reveals that fluorescence measurements can
      both underestimate and overestimate fluctuations in protein levels that arise
      from the stochastic nature of biochemical reactions.

PMID- 18065462
TI  - Redox properties of Thermus thermophilus ba3: different electron-proton coupling
      in oxygen reductases?
AB  - A comprehensive study of the thermodynamic redox behavior of the hemes of the ba3
      enzyme from Thermus thermophilus, a B-type heme-copper oxygen reductase, is
      presented. This enzyme, in contrast to those having a single type of heme, allows
      the B- and A-type hemes to be monitored separately by visible spectroscopy and
      the reduction potential of each heme to be determined unequivocally. The relative
      order of the midpoint reduction potentials of each center changed in the pH range
      from 6 to 8.4, and both hemes present a significant redox-Bohr effect. For
      instance, at pH 7, the midpoint reduction potentials of the hemes B and A3 are
      213 mV and 285 mV, respectively, whereas at pH 8.4, the order is reversed: 246 mV
      for heme B and 199 mV for heme A3. The existence of redox anticooperativity was
      established by introducing a redox interaction parameter in a model of pairwise
      interacting redox centers.

PMID- 18065461
TI  - Investigations of vibrational coherence in the low-frequency region of ferric
      heme proteins.
AB  - Femtosecond coherence spectroscopy is applied to a series of ferric heme protein
      samples. The low-frequency vibrational spectra that are revealed show dominant
      oscillations near 40 cm(-1). MbCN is taken as a typical example of a histidine
      ligated, six-coordinate, ferric heme and a comprehensive spectroscopic analysis
      is carried out. The results of this analysis reveal a new heme photoproduct
      species, absorbing near 418 nm, which is consistent with the photolysis of the
      His(93) axial ligand. The photoproduct undergoes subsequent rebinding/recovery
      with a time constant of approximately 4 ps. The photoproduct lineshapes are
      consistent with a photolysis quantum yield of 75-100%, although the observation
      of a relatively strong six-coordinate heme coherence near 252 cm(-1) (assigned to
      nu(9) in the MbCN Raman spectrum) suggests that the 75% lower limit is much more
      likely. The phase and amplitude excitation profiles of the low-frequency mode at
      40 cm(-1) suggest that this mode is strongly coupled to the MbCN photoproduct
      species and it is assigned to the doming mode of the transient penta-coordinated
      material. The absolute phase of the 40 cm(-1) mode is found to be pi/2 on the red
      side of 418 nm and it jumps to 3pi/2 as excitation is tuned to the blue side of
      418 nm. The absolute phase of the 40 cm(-1) signal is not explained by the
      standard theory for resonant impulsive stimulated Raman scattering. New
      mechanisms that give a dominant momentum impulse to the resonant wavepacket,
      rather than a coordinate displacement, are discussed. The possibilities of heme
      iron atom recoil after photolysis, as well as ultrafast nonradiative decay, are
      explored as potential ways to generate the strong momentum impulse needed to
      understand the phase properties of the 40 cm(-1) mode.

PMID- 18065463
TI  - Static compression of single chondrocytes catabolically modifies single-cell gene
      expression.
AB  - Previous work has established that mechanical forces can lead to quantifiable
      alterations in cell function. However, how forces change gene expression in a
      single cell and the mechanisms of force transmission to the nucleus are poorly
      understood. Here we demonstrate that the gene expression of proteins related to
      the extracellular matrix in single articular chondrocytes is modified by
      compressive forces in a dosage-dependent manner. Increasing force exposure
      catabolically shifts single-cell mRNA levels of aggrecan, collagen IIa, and
      tissue inhibitor of metalloproteinase-1. Cytohistochemistry reveals that the
      majority of strain experienced by the cell is also experienced by the nucleus,
      resulting in considerable changes in nuclear volume and structure. Transforming
      growth factor-beta1 and insulin-like growth factor-I offer mechanoprotection and
      recovery of gene expression of aggrecan and metalloproteinase-1. These results
      suggest that forces directly influence gene transcription and may do so by
      changing chromatin conformation.

PMID- 18065464
TI  - A mathematical model of airway and pulmonary arteriole smooth muscle.
AB  - Airway hyperresponsiveness is a major characteristic of asthma and is believed to
      result from the excessive contraction of airway smooth muscle cells (SMCs).
      However, the identification of the mechanisms responsible for airway
      hyperresponsiveness is hindered by our limited understanding of how calcium
      (Ca2+), myosin light chain kinase (MLCK), and myosin light chain phosphatase
      (MLCP) interact to regulate airway SMC contraction. In this work, we present a
      modified Hai-Murphy cross-bridge model of SMC contraction that incorporates Ca2+
      regulation of MLCK and MLCP. A comparative fit of the model simulations to
      experimental data predicts 1), that airway and arteriole SMC contraction is
      initiated by fast activation by Ca2+ of MLCK; 2), that airway SMC, but not
      arteriole SMC, is inhibited by a slower activation by Ca2+ of MLCP; and 3), that
      the presence of a contractile agonist inhibits MLCP to enhance the Ca2+
      sensitivity of airway and arteriole SMCs. The implication of these findings is
      that murine airway SMCs exploit a Ca2+-dependent mechanism to favor a default
      state of relaxation. The rate of SMC relaxation is determined principally by the
      rate of release of the latch-bridge state, which is predicted to be faster in
      airway than in arteriole. In addition, the model also predicts that oscillations
      in calcium concentration, commonly observed during agonist-induced smooth muscle
      contraction, cause a significantly greater contraction than an elevated steady
      calcium concentration.

PMID- 18065465
TI  - Binding and clustering of glycosaminoglycans: a common property of mono- and
      multivalent cell-penetrating compounds.
AB  - Recent observations in cell culture provide evidence that negatively charged
      glycosaminoglycans (GAGs) at the surface of biological cells bind cationic cell
      penetrating compounds (CPCs) and cluster during CPC binding, thereby contributing
      to their endocytotic uptake. The GAG binding and clustering occur in the low
      micromolar concentration range and suggest a tight interaction between GAGs and
      CPCs, although the relation between binding affinity and specificity of this
      interaction remains to be investigated. We therefore measured the GAG binding and
      clustering of various mono- and multivalent CPCs such as DNA transfection vectors
      (polyethylenimine; 1,2-dioleoyl-3-trimethylammonium-propane), amino acid
      homopolymers (oligoarginine; oligolysine), and cell-penetrating peptides
      (Penetratin; HIV-1 Tat) by means of isothermal titration calorimetry and dynamic
      light scattering. We find that these structurally diverse CPCs share the property
      of GAG binding and clustering. The binding is very tight (microscopic
      dissociation constants between 0.34 and 1.34 microM) and thus biologically
      relevant. The hydrodynamic radius of the resulting aggregates ranges from 78 nm
      to 586 nm, suggesting that they consist of numerous GAG chains cross-linked by
      CPCs. Likewise, the membrane-permeant monovalent cation acridine orange leads to
      GAG binding and clustering, in contrast to its membrane-impermeant structural
      analogs propidium iodide and ethidium bromide. Because the binding and clustering
      of GAGs were found to be a common denominator of all CPCs tested, these
      properties might be helpful to identify further CPCs.

PMID- 18065466
TI  - Analyzing forced unfolding of protein tandems by ordered variates, 2: dependent
      unfolding times.
AB  - Statistical analyses of forced unfolding data for protein tandems, i.e.,
      unfolding forces (force-ramp) and unfolding times (force-clamp), used in single
      molecule dynamic force spectroscopy rely on the assumption that the unfolding
      transitions of individual protein domains are independent (uncorrelated) and
      characterized, respectively, by identically distributed unfolding forces and
      unfolding times. In our previous work, we showed that in the experimentally
      accessible piconewton force range, this assumption, which holds at a lower
      constant force, may break at an elevated force level, i.e., the unfolding
      transitions may become correlated when force is increased. In this work, we
      develop much needed statistical tests for assessing the independence of the
      unobserved forced unfolding times for individual protein domains in the tandem
      and equality of their parent distributions, which are based solely on the
      observed ordered unfolding times. The use and performance of these tests are
      illustrated through the analysis of unfolding times for computer models of
      protein tandems. The proposed tests can be used in force-clamp atomic force
      microscopy experiments to obtain accurate information on protein forced unfolding
      and to probe data on the presence of interdomain interactions. The order
      statistics-based formalism is extended to cover the analysis of correlated
      unfolding transitions. The use of order statistics leads naturally to the
      development of new kinetic models, which describe the probabilities of ordered
      unfolding transitions rather than the populations of chemical species.

PMID- 18065467
TI  - Stabilization of neurotoxic soluble beta-sheet-rich conformations of the
      Alzheimer's disease amyloid-beta peptide.
AB  - An emerging paradigm for degenerative diseases associated with protein
      misfolding, such as Alzheimer's disease, is the formation of a toxic species due
      to structural transitions accompanied by oligomerization. Increasingly, the focus
      in Alzheimer's disease is on soluble oligomeric forms of the amyloid-beta peptide
      (Abeta) as the potential toxic species. Using a variety of methods, we have
      analyzed how sodium dodecyl sulphate (SDS) modulates the folding of Abeta40 and
      42 and found that submicellar concentrations of SDS solubilize Abeta and induce
      structural transitions. Under these conditions, Abeta40 and 42 are
      interconverting oligomeric ensembles with a predominantly beta-sheet structure.
      The Abeta42 soluble oligomers form beta-sheet structures more readily and have
      increased stability compared with Abeta40 under identical conditions. The
      presence of added Cu(2+) significantly promotes and stabilizes the formation of
      the soluble oligomeric beta-sheet structures but these structures are
      nonamyloidogenic. In contrast, in the absence of added Cu(2+), these beta-sheet
      oligomers possess the hallmarks of amyloidogenic structures. These SDS-induced
      beta-sheet forms of Abeta, both in the presence and absence of Cu(2+), are toxic
      to neuronal cells.

PMID- 18065468
TI  - How does intracellular Ca2+ oscillate: by chance or by the clock?
AB  - Ca2+ oscillations have been considered to obey deterministic dynamics for almost
      two decades. We show for four cell types that Ca2+ oscillations are instead a
      sequence of random spikes. The standard deviation of the interspike intervals
      (ISIs) of individual spike trains is similar to the average ISI; it increases
      approximately linearly with the average ISI; and consecutive ISIs are
      uncorrelated. Decreasing the effective diffusion coefficient of free Ca2+ using
      Ca2+ buffers increases the average ISI and the standard deviation in agreement
      with the idea that individual spikes are caused by random wave nucleation. Array
      enhanced coherence resonance leads to regular Ca2+ oscillations with small
      standard deviation of ISIs.

PMID- 18065469
TI  - Spectrin folding versus unfolding reactions and RBC membrane stiffness.
AB  - Spectrin (Sp), a key component of the erythrocyte membrane, is routinely
      stretched to near its fully folded contour length during cell deformations. Such
      dynamic loading may induce domain unfolding as suggested by recent experiments.
      Herein we develop a model to describe the folding/unfolding of spectrin during
      equilibrium or nonequilibrium extensions. In both cases, our model indicates that
      there exists a critical extension beyond which unfolding occurs. We further
      deploy this model, together with a three-dimensional model of the junctional
      complex in the erythrocyte membrane, to explore the effect of Sp unfolding on the
      membrane's mechanical properties, and on the thermal fluctuation of membrane
      attached beads. At large deformations our results show a distinctive strain
      induced unstiffening behavior, manifested in the slow decrease of the shear
      modulus, and accompanied by an increase in bead fluctuation. Bead fluctuation is
      also found to be influenced by mode switching, a phenomenon predicted by our
      three-dimensional model. The amount of stiffness reduction, however, is modest
      compared with that reported in experiments. A possible explanation for the
      discrepancy is the occurrence of spectrin head-to-head disassociation which is
      also included within our modeling framework and used to analyze bead motion as
      observed via experiment.

PMID- 18065470
TI  - Single-molecule measurement of the stiffness of the rigor myosin head.
AB  - The force-extension curve of single myosin subfragment-1 molecules, interacting
      in the rigor state with an actin filament, has been investigated at low [ATP] by
      applying a slow triangle-wave movement to the optical traps holding a bead-actin
      bead dumbbell. In combination with a measurement of the overall stiffness of the
      dumbbell, this allowed characterization of the three extensible elements, the
      actin-bead links and the myosin. Simultaneously, another method, based on an
      analysis of bead position covariance, gave satisfactory agreement. The mean
      covariance-based estimate for the myosin stiffness was 1.79 pN/nm (SD = 0.7
      pN/nm; SE = 0.06 pN/nm (n = 166 myosin molecules)), consistent with a recent
      report (1.7 pN/nm) from rabbit muscle fibers. In the triangle-wave protocol, the
      motion of the trapped beads during interactions was linear within experimental
      error over the physiological range of force applied to myosin (+/-10 pN),
      consistent with a Hookean model; any nonlinear terms could not be characterized.
      Bound states subjected to forces that resisted the working stroke (i.e., positive
      forces) detached at a significantly lower force than when subjected to negative
      forces, which is indicative of a strain-dependent dissociation rate.

PMID- 18065471
TI  - Bistable behavior in a model of the lac operon in Escherichia coli with variable
      growth rate.
AB  - This work is a continuation from another study previously published in this
      journal. Both the former and the present works are dedicated to investigating the
      bistable behavior of the lac operon in Escherichia coli from a mathematical
      modeling point of view. In the previous article, we developed a detailed
      mathematical model that accounts for all of the known regulatory mechanisms in
      this system, and studied the effect of inducing the operon with lactose instead
      of an artificial inducer. In this article, the model is improved to account, in a
      more detailed way, for the interaction of the repressor molecules with the three
      lac operators. A recently discovered cooperative interaction between the CAP
      molecule (an activator of the lactose operon) and Operator 3 (which influences
      DNA folding) is also included in this new version of the model. The growth rate
      dependence on the rate of energy entering the bacteria (in the form of
      transported glucose molecules and of metabolized lactose molecules) is also
      considered. A large number of numerical experiments is carried out with this
      improved model. The results are discussed in regard to the bistable behavior of
      the lactose operon. Special attention is paid to the effect that a variable
      growth rate has on the system dynamics.

PMID- 18065472
TI  - Ligand-stabilized conformational states of human beta(2) adrenergic receptor:
      insight into G-protein-coupled receptor activation.
AB  - G-protein-coupled receptors (GPCRs) are known to exist in dynamic equilibrium
      between inactive- and several active-state conformations, even in the absence of
      a ligand. Recent experimental studies on the beta(2) adrenergic receptor
      (beta(2)AR) indicate that structurally different ligands with varying efficacies
      trigger distinct conformational changes and stabilize different receptor
      conformations. We have developed a computational method to study the ligand
      induced rotational orientation changes in the transmembrane helices of GPCRs.
      This method involves a systematic spanning of the rotational orientation of the
      transmembrane helices (TMs) that are in the vicinity of the ligand for predicting
      the helical rotations that occur on ligand binding. The predicted ligand
      stabilized receptor conformations are characterized by a simultaneous lowering of
      the ligand binding energy and a significant gain in interhelical and receptor
      ligand hydrogen bonds. Using the beta(2)AR as a model, we show that the receptor
      conformational state depends on the structure and efficacy of the ligand for a
      given signaling pathway. We have studied the ligand-stabilized receptor
      conformations of five different ligands, a full agonist, norepinephrine; a
      partial agonist, salbutamol; a weak partial agonist, dopamine; a very weak
      agonist, catechol; and an inverse agonist, ICI-115881. The predicted ligand
      stabilized receptor models correlate well with the experimentally observed
      conformational switches in beta(2)AR, namely, the breaking of the ionic lock
      between R131(3.50) at the intracellular end of TM3 (part of the DRY motif) and
      E268(6.30) on TM6, and the rotamer toggle switch on W286(6.48) on TM6. In
      agreement with trp-bimane quenching experiments, we found that norepinephrine and
      dopamine break the ionic lock and engage the rotamer toggle switch, whereas
      salbutamol, a noncatechol partial agonist only breaks the ionic lock, and the
      weak agonist catechol only engages the rotamer toggle switch. Norepinephrine and
      dopamine occupy the same binding region, between TM3, TM5, and TM6, whereas the
      binding site of salbutamol is shifted toward TM4. Catechol binds deeper into the
      protein cavity compared to the other ligands, making contact with TM5 and TM6. A
      part of the catechol binding site overlaps with those of dopamine and
      norepinephrine but not with that of salbutamol. Virtual ligand screening on
      10,060 ligands on the norepinephrine-stabilized receptor conformation shows an
      enrichment of 38% compared to ligand unbound receptor conformation. These results
      show that ligand-induced conformational changes are important for developing
      functionally specific drugs that will stabilize a particular receptor
      conformation. These studies represent the first step toward a more universally
      applicable computational method for studying ligand efficacy and GPCR activation.

PMID- 18065474
TI  - Locomotive mechanism of Physarum plasmodia based on spatiotemporal analysis of
      protoplasmic streaming.
AB  - We investigate how an amoeba mechanically moves its own center of gravity using
      the model organism Physarum plasmodium. Time-dependent velocity fields of
      protoplasmic streaming over the whole plasmodia were measured with a particle
      image velocimetry program developed for this work. Combining these data with
      measurements of the simultaneous movements of the plasmodia revealed a simple
      physical mechanism of locomotion. The shuttle streaming of the protoplasm was not
      truly symmetric due to the peristalsis-like movements of the plasmodium. This
      asymmetry meant that the transport capacity of the stream was not equal in both
      directions, and a net forward displacement of the center of gravity resulted. The
      generality of this as a mechanism for amoeboid locomotion is discussed.

PMID- 18065473
TI  - Tryptophan fluorescence reveals the presence of long-range interactions in the
      denatured state of ribonuclease Sa.
AB  - Characterizing the denatured state ensemble is crucial to understanding protein
      stability and the mechanism of protein folding. The aim of this research was to
      see if fluorescence could be used to gain new information on the denatured state
      ensemble. Ribonuclease Sa (RNase Sa) contains no Trp residues. We made five
      variants of RNase Sa by adding Trp residues at locations where they are found in
      other members of the microbial ribonuclease family. To better understand the
      protein denatured state, we also studied the fluorescence properties of the
      following peptides: N-acetyl-Trp-amide (NATA), N-acetyl-Ala-Trp-Ala-amide (AWA),
      N-acetyl-Ala-Ala-Trp-Ala-Ala-amide (AAWAA), and the five pentapeptides with the
      same sequence as the Trp substitution sites in RNase Sa. The major conclusions
      are: 1), the wavelength of maximum fluorescence intensity, lambda(max), does not
      differ significantly for the peptides and the denatured proteins; 2), the
      fluorescence intensity at lambda(max), I(F), differs significantly for the five
      Trp containing variants of RNase Sa; 3), the I(F) differences for the denatured
      proteins are mirrored in the peptides, showing that the short-range effects
      giving rise to the I(F) differences in the peptides are also present in the
      proteins; 4) the I(F) values for the denatured proteins are more than 30% greater
      than for the peptides, showing the presence of long-range effects in the
      proteins; 5), fluorescence quenching of Trp by acrylamide and iodide is more than
      50% greater in the peptides than in the denatured proteins, showing that long
      range effects limit the accessibility of the quenchers to the Trp side chains in
      the proteins; and 6), these results show that nonlocal effects in the denatured
      states of proteins influence Trp fluorescence and accessibility significantly.

PMID- 18065475
TI  - Fluorescence correlation spectroscopy of finite-sized particles.
AB  - A theory is presented to study fluorescence correlation spectroscopy for
      particles with size comparable to the beam waist of the observation volume.
      Analytical correlation curves are derived for some experimentally interesting
      particle geometries. It is found that the finiteness of the particle generally
      decreases the value of the correlation amplitude and increases the correlation
      time compared to a point particle model. Furthermore, not only the size but also
      the distribution of fluorophores affects the shape of the correlation function.
      This is experimentally demonstrated with surface and internally labeled
      fluorescent spheres. In addition, experiments are performed on fluorescent
      spheres of different radii to validate the model by comparing the results to
      theoretical predictions.

PMID- 18065476
TI  - The color of lactotroph secretory granules stained with FM1-43 depends on dye
      concentration.
AB  - When pituitary lactotroph granules undergo exocytosis in the presence of FM1-43,
      their cores absorb dye and fluoresce brightly. We report that different granules
      fluoresce with different colors, despite being stained with a single fluorescent
      dye; emission spectra from individual granules show up to a 25 nm difference
      between the greenest and reddest granules. We found a correlation between granule
      color and average fluorescence intensity, suggesting that granule color depends
      upon dye concentration. We confirmed this in two ways: by increasing FM dye
      concentration in granules, which red shifted granule color, and by partially
      photobleaching the FM dye in granules, which green shifted granule color.
      Increasing stimulation intensity (by increasing KCl concentration) increased the
      proportion of red granules, indicating that granules exocytosing during intense
      stimulation bound more dye. This, perhaps, reflects differences in granule core
      maturation and condensation in which mature granules with condensed cores bind
      more FM dye but require more intense stimulation to be released. Concentration
      dependent color shifts of FM dyes may be useful for monitoring aggregation
      processes occurring on a size scale smaller than the optical limit.

PMID- 18065477
TI  - Peptide sequence and conformation strongly influence tryptophan fluorescence.
AB  - This article probes the denatured state ensemble of ribonuclease Sa (RNase Sa)
      using fluorescence. To interpret the results obtained with RNase Sa, it is
      essential that we gain a better understanding of the fluorescence properties of
      tryptophan (Trp) in peptides. We describe studies of N-acetyl-L-tryptophanamide
      (NATA), a tripeptide: AWA, and six pentapeptides: AAWAA, WVSGT, GYWHE, HEWTV,
      EAWQE, and DYWTG. The latter five peptides have the same sequence as those
      surrounding the Trp residues studied in RNase Sa. The fluorescence emission
      spectra, the fluorescence lifetimes, and the fluorescence quenching by acrylamide
      and iodide were measured in concentrated solutions of urea and guanidine
      hydrochloride. Excited-state electron transfer from the indole ring of Trp to the
      carbonyl groups of peptide bonds is thought to be the most important mechanism
      for intramolecular quenching of Trp fluorescence. We find the maximum
      fluorescence intensities vary from 49,000 for NATA with two carbonyls, to 24,400
      for AWA with four carbonyls, to 28,500 for AAWAA with six carbonyls. This
      suggests that the four carbonyls of AWA are better able to quench Trp
      fluorescence than the six carbonyls of AAWAA, and this must reflect a difference
      in the conformations of the peptides. For the pentapeptides, EAWQE has a
      fluorescence intensity that is more than 50% greater than DYWTG, showing that the
      amino acid sequence influences the fluorescence intensity either directly through
      side-chain quenching and/or indirectly through an influence on the conformational
      ensemble of the peptides. Our results show that peptides are generally better
      models for the Trp residues in proteins than NATA. Finally, our results emphasize
      that we have much to learn about Trp fluorescence even in simple compounds.

PMID- 18065478
TI  - The self-assembly, elasticity, and dynamics of cardiac thin filaments.
AB  - Solutions of intact cardiac thin filaments were examined with transmission
      electron microscopy, dynamic light scattering (DLS), and particle-tracking
      microrheology. The filaments self-assembled in solution with a bell-shaped
      distribution of contour lengths that contained a population of filaments of much
      greater length than the in vivo sarcomere size ( approximately 1 mum) due to a
      one-dimensional annealing process. Dynamic semiflexible modes were found in DLS
      measurements at fast timescales (12.5 ns-0.0001 s). The bending modulus of the
      fibers is found to be in the range 4.5-16 x 10(-27) Jm and is weakly dependent on
      calcium concentration (with Ca2+ > or = without Ca2+). Good quantitative
      agreement was found for the values of the fiber diameter calculated from
      transmission electron microscopy and from the initial decay of DLS correlation
      functions: 9.9 nm and 9.7 nm with and without Ca2+, respectively. In contrast, at
      slower timescales and high polymer concentrations, microrheology indicates that
      the cardiac filaments act as short rods in solution according to the predictions
      of the Doi-Edwards chopsticks model (viscosity, eta approximately c(3), where c
      is the polymer concentration). This differs from the semiflexible behavior of
      long synthetic actin filaments at comparable polymer concentrations and
      timescales (elastic shear modulus, G' approximately c(1.4), tightly entangled)
      and is due to the relative ratio of the contour lengths ( approximately 30). The
      scaling dependence of the elastic shear modulus on the frequency (omega) for
      cardiac thin filaments is G' approximately omega(3/4 +/- 0.03), which is thought
      to arise from flexural modes of the filaments.

PMID- 18065479
TI  - Structure of spheroidal HDL particles revealed by combined atomistic and coarse
      grained simulations.
AB  - Spheroidal high-density lipoprotein (HDL) particles circulating in the blood are
      formed through an enzymatic process activated by apoA-I, leading to the
      esterification of cholesterol, which creates a hydrophobic core of cholesteryl
      ester molecules in the middle of the discoidal phospholipid bilayer. In this
      study, we investigated the conformation of apoA-I in model spheroidal HDL (ms
      HDL) particles using both atomistic and coarse-grained molecular dynamics
      simulations, which are found to provide consistent results for all HDL properties
      we studied. The observed small contribution of cholesteryl oleate molecules to
      the solvent-accessible surface area of the entire ms-HDL particle indicates that
      palmitoyloleoylphosphatidylcholines and apoA-I molecules cover the hydrophobic
      core comprised of cholesteryl esters particularly well. The ms-HDL particles are
      found to form a prolate ellipsoidal shape, with sizes consistent with
      experimental results. Large rigid domains and low mobility of the protein are
      seen in all the simulations. Additionally, the average number of contacts of
      cholesteryl ester molecules with apoA-I residues indicates that cholesteryl
      esters interact with protein residues mainly through their cholesterol moiety. We
      propose that the interaction of annular cholesteryl oleate molecules contributes
      to apoA-I rigidity stabilizing and regulating the structure and function of the
      ms-HDL particle.

PMID- 18065480
TI  - Fluorescence fluctuation spectroscopy in the presence of immobile fluorophores.
AB  - Fluorescence contributions from immobile sources present a challenge for
      fluorescence fluctuation spectroscopy (FFS) because the absence of signal
      fluctuations from stationary fluorophores leads to a biased analysis. This is
      especially of concern for cellular FFS studies on proteins that interact with
      immobile structures. Here we present a method that correctly analyzes FFS
      experiments in the presence of immobile sources by exploiting selective
      photobleaching of immobile fluorophores. The fluorescence decay due to
      photobleaching of the immobile species is modeled taking into account the
      nonuniform illumination volume. The experimentally observed decay curve serves to
      separate the mobile and immobile fluorescence contribution, which is used to
      calculate the molecular brightness from the FFS data. We experimentally verify
      this approach in vitro using the fluorescent protein EGFP as our immobilized
      species and a diffusing dye of a different color as the mobile one. For this
      special case, we also use an alternative method of determining the brightness by
      spectrally resolving the two species. By conducting a dilution study, we show
      that the correct parameters are obtained using either technique for a wide range
      of mobile fractions. To demonstrate the application of our technique in living
      cells, we perform experiments using the histone core protein H2B fused with EGFP
      expressed in COS-1 cells. We successfully recovered the brightness of the mobile
      fraction of H2B-EGFP.

PMID- 18065481
TI  - Characterization of the protein unfolding processes induced by urea and
      temperature.
AB  - Correct folding is critical for the biological activities of proteins. As a
      contribution to a better understanding of the protein (un)folding problem, we
      studied the effect of temperature and of urea on peptostreptococcal Protein L
      destructuration. We performed standard molecular dynamics simulations at 300 K,
      350 K, 400 K, and 480 K, both in 10 M urea and in water. Protein L followed at
      least two alternative unfolding pathways. Urea caused the loss of secondary
      structure acting preferentially on the beta-sheets, while leaving the alpha
      helices almost intact; on the contrary, high temperature preserved the beta
      sheets and led to a complete loss of the alpha-helices. These data suggest that
      urea and high temperature act through different unfolding mechanisms, and protein
      secondary motives reveal a differential sensitivity to various denaturant
      treatments. As further validation of our results, replica-exchange molecular
      dynamics simulations of the temperature-induced unfolding process in the presence
      of urea were performed. This set of simulations allowed us to compute the
      thermodynamical parameters of the process and confirmed that, in the
      configurational space of Protein L unfolding, both of the above pathways are
      accessible, although to a different relative extent.

PMID- 18065482
TI  - Probing intranuclear environments at the single-molecule level.
AB  - Genome activity and nuclear metabolism clearly depend on accessibility, but it is
      not known whether and to what extent nuclear structures limit the mobility and
      access of individual molecules. We used fluorescently labeled streptavidin with a
      nuclear localization signal as an average-sized, inert protein to probe the
      nuclear environment. The protein was injected into the cytoplasm of mouse cells,
      and single molecules were tracked in the nucleus with high-speed fluorescence
      microscopy. We analyzed and compared the mobility of single streptavidin
      molecules in structurally and functionally distinct nuclear compartments of
      living cells. Our results indicated that all nuclear subcompartments were easily
      and similarly accessible for such an average-sized protein, and even condensed
      heterochromatin neither excluded single molecules nor impeded their passage. The
      only significant difference was a higher frequency of transient trappings in
      heterochromatin, which lasted only tens of milliseconds. The streptavidin
      molecules, however, did not accumulate in heterochromatin, suggesting
      comparatively less free volume. Interestingly, the nucleolus seemed to exclude
      streptavidin, as it did many other nuclear proteins, when visualized by
      conventional fluorescence microscopy. The tracking of single molecules,
      nonetheless, showed no evidence for repulsion at the border but relatively
      unimpeded passage through the nucleolus. These results clearly show that single
      molecule tracking can provide novel insights into mobility of proteins in the
      nucleus that cannot be obtained by conventional fluorescence microscopy. Our
      results suggest that nuclear processes may not be regulated at the level of
      physical accessibility but rather by local concentration of reactants and
      availability of binding sites.

PMID- 18065483
TI  - Effects of oscillatory electric fields on internal membranes: an analytical
      model.
AB  - We derive an analytical model of the potential differences induced across plasma
      and internal organelle membranes in suspended cells exposed to oscillatory
      electric fields. Multiple shells are modeled using iterative applications of the
      single-shell calculation with mobile charges. This work is motivated, in part, by
      recent results suggesting the ability to use alternating current (ac) fields to
      noninvasively monitor enzyme activity within internal membranes, particularly the
      mitochondrial electron transport chain. Previous work, on induced transmembrane
      voltages in cells subjected to ac fields, has mainly been limited to oscillatory
      potentials across the plasma membrane. Here we first develop a three-membrane
      model, consisting of a plasma membrane surrounding inner and outer membranes
      representing an internal organelle, such as a mitochondrion. Frequency-dependent
      transmembrane potentials are modeled for spherical, weakly conducting membrane
      shells enclosing a conductive cytoplasm surrounding an idealized internal
      organelle. We then use a two-shell model to simulate induced ac membrane
      potentials of a suspended isolated mitochondrion in which the outer membrane is
      usually much more permeable than the inner membrane.

PMID- 18065484
TI  - Optical measurement of mechanical forces inside short DNA loops.
AB  - Knowledge of the mechanical properties of double-stranded DNA (dsDNA) is
      essential to understand the role of dsDNA looping in gene regulation and the
      mechanochemistry of molecular machines that operate on dsDNA. Here, we use a
      newly developed tool, force sensors with optical readout, to measure the forces
      inside short, strained loops composed of both dsDNA and single-stranded DNA. By
      varying the length of the loops and their proportion of dsDNA, it was possible to
      vary their internal forces from 1 pN to >20 pN. Surprisingly, internal loop
      forces changed erratically as the amount of dsDNA was increased for a given loop
      length, with the effect most notable in the smallest loop (57 nucleotides). Monte
      Carlo simulations based on the helical wormlike chain model accurately predict
      internal forces when more than half of the loop is dsDNA but fail otherwise.
      Mismatches engineered into the double-stranded regions increased flexibility,
      suggesting that Watson-Crick basepaired dsDNA can withstand high compressive
      forces without recourse to multibase melts. Fluorescence correlation spectroscopy
      further excluded transient melting (microsecond to millisecond duration) as a
      mechanism for relief of compressive forces in the tested dsDNAs. DNA loops with
      integrated force sensors may allow the comprehensive mapping of the elasticity of
      short dsDNAs as a function of both sequence and salt.

PMID- 18065485
TI  - Mechanical dyssynchrony by 3D echo correlates with acute haemodynamic response to
      biventricular pacing in heart failure patients.
AB  - AIMS: One-third of dilated cardiomyopathy patients receiving a biventricular
      pacing-device do not respond to this form of therapy. Therefore, the utility of
      mechanical dyssynchrony by real-time 3D echocardiography (RT3DE) for predicting
      systolic response to biventricular pacing, of which maximal rate of pressure rise
      (dP/dt(max)) served as the gold-standard, was evaluated. METHODS AND RESULTS:
      Seventeen consecutive heart failure patients (aged 64 +/- 10 years, 8 male, 6
      ischaemic cardiomyopathy, mean QRS duration 136 +/- 32 ms) underwent RT3DE and
      biventricular pacing. Post-processing software provided data of global left
      ventricular (LV) function and the systolic dyssynchrony index of 17 LV segments
      (SDI(17), %) for mechanical dyssynchrony. During biventricular pacing, percentual
      change in dP/dt(max) compared to the non-pacing mode, DeltadP/dt(max) was
      measured invasively with conductance catheters. LV ejection fraction was 31 +/-
      10%, SDI(17) was 10.2 +/- 4.2% and percentual DeltadP/dt(max) during
      biventricular pacing was 14.5 +/- 12.4. A significant correlation (r = 0.729, P =
      0.001) was found between SDI(17) and percentual DeltadP/dt(max), and between QRS
      duration and percentual DeltadP/dt(max) (r = 0.721, P = 0.001). CONCLUSION: The
      present study suggests that mechanical dyssynchrony measured by RT3DE shows a
      good correlation with invasively determined acute haemodynamic response to
      biventricular pacing in patients with symptomatic dilated cardiomyopathy. Future
      studies are needed to further define the clinical utility of RT3DE in identifying
      patients who are most likely to respond to cardiac resynchronization therapy.

PMID- 18065486
TI  - "Contrasting patterns of selection at Pinus pinaster Ait. Drought stress
      candidate genes as revealed by genetic differentiation analyses".
AB  - The importance of natural selection for shaping adaptive trait differentiation
      among natural populations of allogamous tree species has long been recognized.
      Determining the molecular basis of local adaptation remains largely unresolved,
      and the respective roles of selection and demography in shaping population
      structure are actively debated. Using a multilocus scan that aims to detect
      outliers from simulated neutral expectations, we analyzed patterns of nucleotide
      diversity and genetic differentiation at 11 polymorphic candidate genes for
      drought stress tolerance in phenotypically contrasted Pinus pinaster Ait.
      populations across its geographical range. We compared 3 coalescent-based
      methods: 2 frequentist-like, including 1 approach specifically developed for
      biallelic single nucleotide polymorphisms (SNPs) here and 1 Bayesian. Five genes
      showed outlier patterns that were robust across methods at the haplotype level
      for 2 of them. Two genes presented higher F(ST) values than expected (PR-AGP4 and
      erd3), suggesting that they could have been affected by the action of
      diversifying selection among populations. In contrast, 3 genes presented lower
      F(ST) values than expected (dhn-1, dhn2, and lp3-1), which could represent
      signatures of homogenizing selection among populations. A smaller proportion of
      outliers were detected at the SNP level suggesting the potential functional
      significance of particular combinations of sites in drought-response candidate
      genes. The Bayesian method appeared robust to low sample sizes, flexible to
      assumptions regarding migration rates, and powerful for detecting selection at
      the haplotype level, but the frequentist-like method adapted to SNPs was more
      efficient for the identification of outlier SNPs showing low differentiation.
      Population-specific effects estimated in the Bayesian method also revealed
      populations with lower immigration rates, which could have led to favorable
      situations for local adaptation. Outlier patterns are discussed in relation to
      the different genes' putative involvement in drought tolerance responses, from
      published results in transcriptomics and association mapping in P. pinaster and
      other related species. These genes clearly constitute relevant candidates for
      future association studies in P. pinaster.

PMID- 18065487
TI  - Diversifying selection and concerted evolution of a type IV secretion system in
      Bartonella.
AB  - We have studied the evolution of a type IV secretion system (T4SS), in
      Bartonella, which is thought to have changed function from conjugation to
      erythrocyte adherence following a recent horizontal gene transfer event. The
      system, called Trw, is unique among T4SSs in that genes encoding both exo- and
      intracellular components are located within the same duplicated fragment. This
      provides an opportunity to study the influence of selection on proteins involved
      in host-pathogen interactions. We sequenced the trw locus from several strains of
      Bartonella henselae and investigated its evolutionary history by comparisons to
      other Bartonella species. Several instances of recombination and gene conversion
      events where detected in the 2- to 5-fold duplicated gene fragments encompassing
      trwJIH, explaining the homogenization of the anchoring protein TrwI and the
      divergence of the minor pilus protein TrwJ. A phylogenetic analysis of the 7- to
      8-fold duplicated gene coding for the major pilus protein TrwL displayed 2
      distinct clades, likely representing a subfunctionalization event. The analyses
      of the B. henselae strains also identified a recent horizontal transfer event of
      almost the complete trwL region. We suggest that the switch in function of the
      T4SS was mediated by the duplication of the genes encoding pilus components and
      their diversification by combinatorial sequence shuffling within and among
      genomes. We suggest that the pilus proteins have evolved by diversifying
      selection to match a divergent set of erythrocyte surface structures, consistent
      with the trench warfare coevolutionary model.

PMID- 18065488
TI  - Analysis of nuclear receptor pseudogenes in vertebrates: how the silent tell
      their stories.
AB  - Transcription factor pseudogenes have not been systematically studied before.
      Nuclear receptors (NRs) constitute one of the largest groups of transcription
      factors in animals (e.g., 48 NRs in human). The availability of whole-genome
      sequences enables a global inventory of the NR pseudogenes in a number of
      vertebrate model organisms. Here we identify the NR pseudogenes in 8 vertebrate
      organisms and make our results available online at http://www.pseudogene.org/nr.
      The assignments reveal that NR pseudogenes as a group have characteristics
      related to generation and distribution contrary to expectations derived from
      previous large-scale pseudogene studies. In particular, 1) despite its large
      size, the NR gene family has only a very small number of pseudogenes in each of
      the vertebrate genomes examined; 2) despite the low transcription levels of NR
      genes, except for one, all other NR pseudogenes identified in this study are
      retropseudogenes; and 3) no duplicated NR pseudogenes are found, contrary to the
      fact that the NR gene family was expanded through several waves of gene
      duplication events. Our analyses further reveal a number of interesting aspects
      of NR pseudogenes. Specifically, through careful sequence analysis, we identify
      remnant introns in 2 mouse retropseudogenes, psiRev-erbbeta and psiLRH1.
      Generated from partially processed pre-mRNAs, they appear to be rare examples of
      highly unusual "semiprocessed" pseudogenes. Second, by comparing the genomic
      sequences, we uncover a pseudogene that is unique to the human lineage relative
      to chimpanzee. Generated by a recent duplication of a segment in the human
      genome, this pseudogene is a "duplicated-processed" pseudogene, belonging to a
      new pseudogene species. Finally, FXRbeta was nonfunctionalized in the human
      lineage and thus appears to be an example of a rare unitary pseudogene. By
      comparing orthologous sequences, we dated the FXR-FXRbeta duplication and the
      nonfunctionalization of FXRbeta in primates.

PMID- 18065489
TI  - The naphthoquinones, vitamin K3 and its structural analogue plumbagin, are
      substrates of the multidrug resistance linked ATP binding cassette drug
      transporter ABCG2.
AB  - Vitamin K3 (menadione; 2-methyl-1,4-naphthoquinone) is a structural precursor of
      vitamins K1 and K2, which are essential for blood clotting. The naturally
      occurring structural analogue of this vitamin, plumbagin (5-hydroxy-menadione),
      is known to modulate cellular proliferation, apoptosis, carcinogenesis, and
      radioresistance. We here report that both vitamin K3 and plumbagin are substrates
      of the multidrug resistance-linked ATP binding cassette drug transporter, ABCG2.
      Vitamin K3 and plumbagin specifically inhibited the ABCG2-mediated efflux of
      mitoxantrone but did not have any effect on the ABCB1-mediated efflux of
      rhodamine 123. This inhibition of ABCG2 function was due to their interaction at
      the substrate-binding site(s). Vitamin K3 and plumbagin inhibited the binding of
      [(125)I]iodoarylazidoprazosin, a substrate of ABCG2, to this transporter in a
      concentration-dependent manner with IC(50) values of 7.3 and 22.6 micromol/L,
      respectively, but had no effect on the binding of the photoaffinity analogue to
      ABCB1. Both compounds stimulated ABCG2-mediated ATP hydrolysis and also inhibited
      the mitoxantrone-stimulated ATPase activity of the ABCG2 transporter, but did not
      have any significant effect on the ATPase activity of ABCB1. In a cytotoxicity
      assay, ABCG2-expressing HEK cells were 2.8- and 2.3-fold resistant to plumbagin
      and vitamin K3, respectively, compared with the control cells, suggesting that
      they are substrates of this transporter. Collectively, these data show for the
      first time that vitamin K3 is a substrate of the ABCG2 transporter. Thus, ABCG2
      may have a role in the regulation of vitamin K3 levels in the body. In addition,
      vitamin K3 and its structural derivative, plumbagin, could potentially be used to
      modulate ABCG2 function.

PMID- 18065490
TI  - Extrinsic pathway- and cathepsin-dependent induction of mitochondrial dysfunction
      are essential for synergistic flavopiridol and vorinostat lethality in breast
      cancer cells.
AB  - The present studies have determined whether interactions between the cyclin
      dependent kinase inhibitor flavopiridol and the histone deacetylase inhibitor
      suberoylanilide hydroxamic acid (SAHA; vorinostat; Zolinza) occur in breast
      cancer cells. MDA-MB-231 and MCF7 cells were treated with flavopiridol (25-100
      nmol/L) and vorinostat (125-500 nmol/L) in vitro, and mechanisms of cell killing
      were determined. Concurrent treatment of cells with flavopiridol and vorinostat
      or treatment of cells with flavopiridol followed by vorinostat promoted cell
      killing in a greater than additive fashion. Similar data were obtained with the
      CDK inhibitor roscovitine. Flavopiridol suppressed c-FLIP-l/s and BCL-xL
      expression, whereas vorinostat reduced expression of BCL-xL, and combined
      exposure to flavopiridol and vorinostat reduced MCL-1 and X-chromosome-linked
      inhibitor of apoptosis protein (XIAP) levels. Pharmacologic or genetic inhibition
      of caspase-8 reduced flavopiridol toxicity, but abolished killing by vorinostat
      and cell death caused by the vorinostat/flavopiridol regimen. Loss of BAX/BAK
      function or loss of BID function modestly reduced flavopiridol toxicity, but
      abolished vorinostat-mediated potentiation of flavopiridol toxicity, as did
      inhibition of caspase-9. Inhibition and/or deletion of cathepsin B function
      significantly attenuated vorinostat/flavopiridol lethality. Flavopiridol
      suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) and AKT activity
      and expression of activated forms of AKT and mitogen-activated protein/ERK kinase
      1 maintained c-FLIP-l/s, BCL-xL, and XIAP expression and protected cells against
      flavopiridol/vorinostat lethality. Overexpression of c-FLIP-s and BCL-xL
      abolished the lethality of flavopiridol/vorinostat. Collectively, these data
      argue that flavopiridol enhances the lethality of vorinostat in breast cancer
      cells in part through the inhibition of AKT and ERK1/2 function, leading to
      reduced expression of multiple inhibitors of the extrinsic and intrinsic
      apoptosis pathways, as well as activation of cathepsin protease-dependent
      pathways.

PMID- 18065491
TI  - Inhibition of Src family kinases enhances retinoic acid induced gene expression
      and myeloid differentiation.
AB  - Treatment of acute promyelocytic leukemia with retinoic acid (RA) results in
      differentiation of the leukemic cells and clinical remission. However, the
      cellular factors that regulate RA-induced myeloid differentiation are largely
      unknown, and other forms of acute myelogenous leukemia (AML) do not respond to
      this differentiation therapy. A greater understanding of the molecules that
      positively or negatively regulate RA-induced differentiation should facilitate
      the development of more effective differentiation therapies. In this study, we
      investigated the potential role of Src family kinases (SFK) in the regulation of
      RA-induced gene expression and myeloid differentiation. We report that inhibition
      of SFKs markedly enhanced RA-induced differentiation in myeloid cell lines and
      primary AML cells, as assessed by flow-cytometric analysis of cell surface
      markers, morphologic analysis, and nitroblue tetrazolium reduction. In addition,
      inhibition of SFKs enhanced expression from retinoic acid receptor (RAR) target
      genes encoding CCAAT/enhancer binding protein epsilon (C/EBPepsilon), PU.1,
      intercellular adhesion molecule-1 (ICAM-1), and cathepsin D. Moreover, a
      constitutively active Src inhibited RAR-dependent transcription, whereas a kinase
      dead Src exerted little effect. These studies provide the first demonstration
      that SFKs act to negatively regulate RA-induced gene expression and myeloid
      differentiation and suggest that the combination of SFK inhibition and RA
      treatment may be therapeutically beneficial in AML.

PMID- 18065492
TI  - The synthetic oleanane triterpenoid, CDDO-methyl ester, is a potent
      antiangiogenic agent.
AB  - We show that the synthetic oleanane triterpenoid, CDDO-methyl ester (CDDO-Me;
      methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate) is an effective agent for
      suppressing angiogenesis, both in cell culture and in vivo. The potency of CDDO
      Me is particularly striking when dosed in vivo to inhibit the angiogenic effects
      of vascular endothelial growth factor and tumor necrosis factor-alpha in Matrigel
      sponge assays; activity is seen at i.p. doses of CDDO-Me as low as 0.003 mg/kg of
      body weight. If the Matrigel sponges are impregnated with CDDO-Me just before
      implantation in the mice, picomolar doses of CDDO-Me will suppress angiogenesis.
      CDDO-Me also inhibits growth of endothelial cells in monolayer cultures and
      suppresses neovascular morphogenesis in three-dimensional cultures, but
      significantly higher doses (50-200 nmol/L) are required. We also show
      antiangiogenic effects of CDDO-Me on xenografts of Kaposi's sarcoma cells in
      immunocompromised mice, using CD31 as a marker. Several known individual
      molecular targets of CDDO-Me and related triterpenoids that are relevant to all
      of these findings include nuclear factor-kappaB signaling, signal transducers and
      activators of transcription signaling, and transforming growth factor-beta
      signaling, as well as Keap1, the endogenous inhibitor of the transcription factor
      Nrf2. However, the particularly potent antiangiogenic activity seen in vivo in
      the present experiments suggest that CDDO-Me, as an angioprevention agent, may be
      interacting with an entire network of molecular and cellular targets, rather than
      at a single molecular locus or in a single-cell type.

PMID- 18065493
TI  - Selective targeting of death receptor 5 circumvents resistance of MG-63
      osteosarcoma cells to TRAIL-induced apoptosis.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a tumor necrosis
      factor superfamily member, targets death receptors and selectively kills
      malignant cells while leaving normal cells unaffected. However, unlike most
      cancers, many osteosarcomas are resistant to TRAIL. To investigate this
      resistance, we characterized the response of MG-63 osteosarcoma cells and hPOB
      tert osteoblast-like cells to TRAIL and agonist antibodies to death receptor 4
      (DR4) and death receptor 5 (DR5). We found that MG-63 osteosarcoma cells and hPOB
      tert osteoblast-like cells show no or very little response to TRAIL or a DR4
      agonist, but MG-63 cells undergo apoptosis in response to a DR5 agonist. Analysis
      of TRAIL receptor expression showed that normal osteoblastic and osteosarcoma
      cells express a variety of TRAIL receptors but this does not correlate to TRAIL
      responsiveness. Production of the soluble decoy receptor osteoprotegerin also
      could not explain TRAIL resistance. We show that TRAIL activates the canonical
      caspase-dependent pathway, whereas treatment with cycloheximide increases the
      sensitivity of MG-63 cells to TRAIL and anti-DR5 and can also sensitize hPOB-tert
      cells to both agents. Proapoptotic and antiapoptotic protein expression does not
      significantly differ between MG-63 and hPOB-tert cells or change following
      treatment with TRAIL or anti-DR5. However, sequencing the death domain of DR4 in
      several osteoblast-like cells showed that MG-63 osteosarcoma cells are
      heterozygous for a dominant-negative mutation, which can confer TRAIL resistance.
      These results suggest that although the dominant-negative form of the receptor
      may block TRAIL-induced death, an agonist antibody to the active death receptor
      can override cellular defenses and thus provide a tailored approach to treat
      resistant osteosarcomas.

PMID- 18065494
TI  - Pulmonary artery growth after Norwood and bidirectional Glenn procedure.
AB  - A 19-day-old boy diagnosed with hypoplastic left heart syndrome underwent stage I
      bilateral pulmonary artery banding and main pulmonary artery-to-descending aorta
      shunt. A restrictive atrial septal defect existing before stage I recurred after
      balloon atrioseptostomy. After stage II Norwood and bidirectional Glenn procedure
      at age nine months, the Nakata index decreased to 73 mm(2)/m(2) (pulmonary artery
      mean pressure: 15 mmHg) and multiple systemic venous collaterals developed. Thus,
      we instituted oral sildenafil medication, and undertook surgical chest
      subcutaneous venous ligation and coil embolizations. Three years later, the
      Nakata index had increased to 117 mm(2)/m(2) (pulmonary artery mean pressure: 13
      mmHg) and a Fontan procedure was successfully performed.

PMID- 18065495
TI  - p21-activated kinase 1 promotes soluble mutant huntingtin self-interaction and
      enhances toxicity.
AB  - Huntington's disease (HD) is caused by a polyglutamine (polyQ) expansion in the
      huntingtin (htt) protein. While aggregation is a pathological hallmark of HD and
      related polyQ expansion diseases, the role of aggregates has been disputed. Here
      we report that p21-activated kinase 1 (Pak1) binds to htt in vivo and in vitro.
      Pak1 colocalized with mutant htt (muhtt) aggregates in cell models and in human
      HD brains. Pak1 overexpression enhanced the aggregation of muhtt. Furthermore, we
      observed SDS-soluble wild-type htt (wthtt)-wthtt, wthtt-muhtt and muhtt-muhtt
      interactions, which were enhanced by the presence of Pak1. We show that Pak1
      overexpression enhanced htt toxicity in cell models and neurons in parallel with
      its ability to promote aggregation, while Pak1 knockdown suppressed both
      aggregation and toxicity. Overexpression of either kinase-dead or wild-type Pak
      enhanced both aggregation and toxicity. Our data reveal a novel mechanism
      regulating muhtt oligomerization and toxicity and suggest that pathology may be
      at least partly dependent on soluble muhtt-muhtt interactions.

PMID- 18065496
TI  - Regulation of the PTEN promoter by statins and SREBP.
AB  - Germline mutations in the tumor-suppressor gene PTEN predispose to heritable
      breast cancer. The transcription factor peroxisome proliferator-activated
      receptor-gamma (PPARgamma) has also been implicated as a tumor suppressor
      pertinent to a range of neoplasias, including breast cancer. We previously
      demonstrated that lovastatin may signal through PPARgamma and directly upregulate
      PTEN expression at the transcriptional level. In our current study, we show that
      simvastatin, pravastatin and fluvastatin can induce PTEN expression in a dose
      dependent manner. This resulted from an increase in PTEN mRNA indicating
      transcriptional upregulation. In addition, we observed, for the first time, that
      upregulation of sterol response element-binding protein (SREBP), known to induce
      PPARgamma expression, can increase PTEN expression. Using reporter assays, we
      observed that both the statins and SREBP could specifically induce PPARgamma
      mediated transcription. However, the statins do not appear to signal through
      SREBP. Furthermore, our results indicate that SREBP utilizes PPARgamma's
      transcriptional activity to induce PTEN transcription, whereas the statins signal
      through PPARgamma's protein activity to upregulate PTEN expression. Overall, our
      observations suggest that statins signal through another transcription factor, in
      a PPARgamma-dependent manner, which in turn induces PTEN transcription. We,
      therefore, studied the full-length PTEN promoter through serial deletion reporter
      assays and electromobility shift assays and identified a region between -854 and 
      791 that binds an as-yet-unidentified transcription factor, through which the
      statins induce PTEN expression. Since PTEN is constitutively active, our data
      indicate it may be worthwhile to examine statin and SREBP stimulation as
      mechanisms to increase PTEN expression for therapeutic and preventative
      strategies in cancer, diabetes mellitus and cardiovascular disease.

PMID- 18065497
TI  - Ubiquitination of alpha-synuclein by Siah-1 promotes alpha-synuclein aggregation
      and apoptotic cell death.
AB  - Point mutations and gene multiplication of alpha-synuclein cause autosomal
      dominant familial Parkinson's disease (PD). Moreover, alpha-synuclein- and
      ubiquitin-positive inclusion bodies are the pathological hallmarks of PD and
      several other neurodegenerative diseases, such as dementia with Lewy bodies and
      multiple system atrophy. Despite the presence of ubiquitinated alpha-synuclein
      species in Lewy bodies, the regulation of alpha-synuclein ubiquitination and its
      role in Lewy body formation and neurodegeneration remain poorly understood. Here,
      we report that alpha-synuclein interacts and colocalizes with mammalian seven in
      absentia homologue-1 (Siah-1), a RING-type E3 ubiquitin-protein ligase. Siah-1
      binds the brain-enriched E2 ubiquitin-conjugating enzyme UbcH8 and facilitates
      mono- and di-ubiquitination of alpha-synuclein in vivo. The ubiquitination of
      alpha-synuclein by Siah-1 is disrupted by the PD-linked A30P mutation but not by
      A53T mutation. We find that Siah-1-mediated ubiquitination does not target alpha
      synuclein for degradation by the proteasome, but rather, it promotes alpha
      synuclein aggregation and enhances alpha-synuclein toxicity. Our findings suggest
      that Siah-1-mediated alpha-synuclein ubiquitination may play a critical role in
      Lewy body formation and PD pathogenesis.

PMID- 18065498
TI  - COMP: a candidate molecule in the pathogenesis of systemic sclerosis with a
      potential as a disease marker.
AB  - OBJECTIVE: Cartilage oligomeric matrix protein (COMP), primarily found in
      cartilage, is thought to be an important regulator of assembly and maintenance of
      the fibrillar collagen I and II networks. Recently, COMP was shown to be produced
      by skin fibroblasts from patients with systemic sclerosis (SSc, or scleroderma).
      The purpose of this study was to examine whether COMP is released from skin to
      serum in patients with SSc, and may serve as indicator of activity of skin
      involvement. METHODS: Serum COMP levels were measured by enzyme linked
      immunosorbent assay in patients with SSc whose skin involvement was assessed with
      the modified Rodnan skin score (mRss) and high frequency ultrasound. The presence
      of COMP in skin biopsies was assessed by Western blot using a monoclonal antibody
      specific for the very C-terminal end of human COMP. RESULTS: Serum COMP
      correlated to skin involvement as measured by the mRss (n = 70; r(S) = 0.60;
      p<0.001), to skin thickness measured by ultrasound (n = 88; r(S) = 0.55; p<0.001)
      and inversely to skin echogenicity measured by ultrasound (n = 88; r(S) = -0.40;
      p<0.001). In 70 patients followed longitudinally there was a correlation between
      changes in serum COMP (n = 307) and changes in mRss (r(S) = 0.35; p = 0.008). In
      individual patients monitored with repeated measurements, serum COMP changes
      closely paralleled changes in mRss. A C-terminal COMP fragment, with an apparent
      molecular mass of 56 kDa, was identified in SSc skin biopsies, while no COMP
      reactivity was detected in normal skin. CONCLUSION: The high turnover of COMP in
      SSc skin suggests a pathophysiological role. Serum COMP shows promise as a new
      biomarker in SSc.

PMID- 18065499
TI  - High bone turnover is associated with accelerated bone loss but not with
      increased fracture risk in men aged 50 and over: the prospective MINOS study.
AB  - OBJECTIVES: The association of bone turnover markers (BTM) with bone loss and
      fracture risk in men is poorly studied. The morphological basis of such a
      relationship is unknown. The objective of this study was to evaluate the
      association between baseline BTM levels and subsequent bone loss and fracture
      risk in men. METHODS: This study is a prospective 7.5-year follow-up of the
      cohort composed of 723 men aged 50-85 years. Serum concentrations of osteocalcin,
      bone alkaline phosphatase (BAP), procollagen type I N-terminal propeptide, C
      terminal telopeptide of type I collagen (beta-CTX-I) and urinary excretion of
      deoxypyridinoline and beta-CTX-I were measured at baseline. Every 18 months,
      incident fractures were recorded and bone mineral density (BMD) was measured by
      dual energy x ray absorptiometry DXA (spine, hip, distal forearm, whole body).
      RESULTS: Increase in BTM levels was associated with faster bone loss at the level
      of the trochanter, whole body and distal forearm. At the level of the distal
      radius and the ulna, increase in the serum BAP and beta-CTX-I levels were
      associated with faster apparent, net and estimated endosteal bone mineral loss.
      BTM levels did not correlate with the periosteal expansion rate. BTMs were
      significantly associated with bone mineral loss but their predictive power was
      poor. BTMs did not predict incident fractures. CONCLUSIONS: In men aged 50 and
      over, accelerated bone turnover is associated with greater endosteal bone mineral
      loss. From a practical point of view, BTMs cannot be used for the prediction of
      accelerated bone loss or fractures in the clinical management of osteoporosis in
      men.

PMID- 18065500
TI  - The FCRL3 -169T>C polymorphism is associated with rheumatoid arthritis and shows
      suggestive evidence of involvement with juvenile idiopathic arthritis in a
      Scandinavian panel of autoimmune diseases.
AB  - BACKGROUND AND OBJECTIVES: The Fc receptor-like 3 (FCRL3) gene -169T>C single
      nucleotide polymorphism (SNP) has been reported to be associated with several
      autoimmune diseases (AIDs) in Japanese populations. However, association results
      in other populations have been conflicting. Therefore, we investigated this SNP
      in a Scandinavian panel of AIDs. METHODS: We genotyped patients with rheumatoid
      arthritis (RA; n = 708), juvenile idiopathic arthritis (JIA; n = 524), systemic
      lupus erythaematosus (SLE; n = 166), ulcerative colitis (UC; n = 335), primary
      sclerosing cholangitis (PSC; n = 365), Crohn disease (CD; n = 149), a healthy
      control group (n = 1030) and 425 trio families with type 1 diabetes (T1D).
      Statistical analysis consisted of case-control and family-based association
      tests. RESULTS: RA was associated with the C allele (odds ratio (OR) = 1.16, 95%
      CI 1.01 to 1.33) and the CC genotype (OR = 1.30, 95% CI 1.01 to 1.67) of the
      FCRL3 -169T>C SNP in our material. Suggestive evidence for association was also
      found for JIA (CC genotype: OR = 1.30, 95% CI 0.99 to 1.70), and clinical
      subgroup analysis indicated that this was connected to the polyarticular
      subgroup. No significant association was found with SLE, UC, CD, PSC or T1D. In
      patients with RA, we found no significant interaction between the FCRL3 -169T>C
      and PTPN22 1858C>T SNPs, nor between the FCRL3 -169CC genotype and IgM-rheumatoid
      factor or anti-cyclic citrullinated peptide titre levels. CONCLUSION: We found an
      association between the FCRL3 -169T>C SNP and RA, and suggestive evidence for
      involvement with JIA, in a Norwegian population. These findings lend support for
      a role for this SNP in RA across ethnically diverse populations, and warrant
      follow-up studies in JIA.

PMID- 18065501
TI  - A conservative, single-amino acid substitution in the second cytoplasmic domain
      of the human Serotonin2C receptor alters both ligand-dependent and -independent
      receptor signaling.
AB  - The post-transcriptional process of mRNA editing changes up to three amino acids
      in the second intracellular domain (i2) of the serotonin(2C) (5-HT(2C)) receptor
      and alters some signaling characteristics of the receptor. Here, we report that
      the substitution of valine for isoleucine (I156V; 5-HT(2C-VNI)), which occurs
      naturally as a result of mRNA editing, alters both ligand-dependent and 
      independent signaling. Agonist functional selectivity at the 5-HT(2C-VNI)
      receptor differed from the nonedited 5-HT(2C-INI) receptor. Ligands with
      selectivity for phospholipase C (PLC) signaling in 5-HT(2C-INI) cells retained
      this selectivity in 5-HT(2C-VNI)-expressing cells. However, ligands with
      selectivity for phospholipase A2 (PLA2) signaling in 5-HT(2C-INI) cells lost the
      capacity for preferential PLA2 activation in 5-HT(2C-VNI) cells. Maximal PLC
      responses elicited by 5-HT (full agonist) and lysergic acid diethylamide and 2,5
      dimethoxy-4-iodophenylisopropylamine (partial agonists) at edited receptors (5
      HT(2C-VNI), 5-HT(2C-VSV), and 5-HT(2C-VGV)) were not different from 5-HT(2C-INI)
      receptors, suggesting that the capacity of the agonist-occupied receptor to
      couple to G(q/11) proteins was not different. Ligand-independent (i.e.,
      constitutive) receptor activity toward PLC for the 5-HT(2C-VNI) receptor was
      markedly reduced to a level similar to that for the fully edited 5-HT(2C-VSV)
      isoform. However, there was no difference in the thermal stability of the edited
      receptors, suggesting that mRNA editing does not alter the capacity of receptors
      to adopt active conformations. These results indicate that a conservative change
      in one amino acid (I156V) located in i2 of the 5-HT(2C) receptor produces
      profound changes in receptor function that differ depending upon whether the
      receptor is unoccupied or occupied by agonist.

PMID- 18065502
TI  - Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine
      metabolism in humans and mice.
AB  - Selegiline (l-deprenyl) is in clinical treatment trials as a potential smoking
      cessation drug. We investigated the affect of selegiline and its metabolites on
      nicotine metabolism. In mice, selegiline was a potent inhibitor of nicotine
      metabolism in hepatic microsomes and cDNA-expressed CYP2A5; the selegiline
      metabolites desmethylselegiline, l-methamphetamine, and l-amphetamine, also
      inhibited nicotine metabolism. Pretreatment with selegiline and
      desmethylselegiline increased inhibition (IC(50)) in microsomes by 3.3- and 6.1
      fold, respectively. In mice in vivo, selegiline increased AUC (90.7 +/- 5.8
      versus 57.4 +/- 5.3 ng/h/ml, p < 0.05), decreased clearance (4.6 +/- 0.4 versus
      7.3 +/- 0.3 ml/min, p < 0.05), and increased elimination half-life (12.5 +/- 6.3
      versus 6.6 +/- 1.4 min, p < 0.05) of nicotine. In vitro, selegiline was a potent
      inhibitor of human nicotine metabolism in hepatic microsomes and cDNA-expressed
      CYP2A6; desmethylselegiline and l-amphetamine also inhibited nicotine metabolism.
      Selegiline preincubation increased inhibition in microsomes (3.7-fold) and CYP2A6
      (14.8-fold); the K(i) for CYP2A6 was 4.2 muM. Selegiline dose- and time
      dependently inhibited nicotine metabolism by CYP2A6 (K(i) = 15.6 +/- 2.7 muM;
      k(inact) = 0.34 +/- 0.04 min(-1)), and the inhibition was irreversible in the
      presence of NADPH, indicating that it is a mechanism-based inhibitor of CYP2A6.
      Thus, inhibition of mouse nicotine metabolism by selegiline was competitive in
      vitro and significantly increased plasma nicotine in vivo. In humans, where
      selegiline is both a competitive and mechanism-based inhibitor, it is likely to
      have even greater effects on in vivo nicotine metabolism. Our findings suggest
      that an additional potential mechanism of selegiline in smoking cessation is
      through inhibition of nicotine metabolism.

PMID- 18065503
TI  - Effects of age and symptom status on silent ischemic lesions after carotid
      stenting with and without the use of distal filter devices.
AB  - BACKGROUND AND PURPOSE: The routine use of distal filter devices during carotid
      angioplasty and stent placement (CAS) is controversial. The aim of this study was
      to analyze their effects on the incidence of new diffusion-weighted imaging (DWI)
      lesions as surrogate markers for stroke in important subgroups. MATERIALS AND
      METHODS: DWI was performed immediately before and after CAS in 68 patients with
      and 175 without protection, and patients were further subdivided according to
      their age or symptom status. RESULTS: The proportion of patients with new
      ipsilateral DWI lesion(s) was significantly lower after protected versus
      unprotected CAS (52% versus 68%), as well as in symptomatic patients (56% versus
      74%) or those at or younger than 75 years of age (46% versus 67%; all P < .05).
      Similarly, the total number of lesions was significantly lower after protected
      versus unprotected CAS (median, 1; interquartile range [IQR], 0-2; versus median,
      1; IQR 0-4.75) and in symptomatic patients (median, 1; IQR, 0-3; versus median,
      2; IQR, 0-6) or those at or younger than 75 years of age (median, 0; IQR, 0-2;
      versus median, 1; IQR, 0-4; all P < .05). In contrast, for asymptomatic patients
      (48% versus 52%; P = .8; median, 0; IQR, 0-2; versus median, 1; IQR, 0-2.5; P =
      .6) or those older than 75 years of age (73% versus 69%; P = .7; median, 1; IQR,
      0-4; versus median, 1.5; IQR, 0-5.75; P = .6), the proportion of patients with
      new lesion(s) and the total number of these lesions were not significantly
      different between protected and unprotected CAS. CONCLUSIONS: The use of distal
      filter devices generally reduces the incidence of new DWI lesions; however, this
      beneficial effect might not necessarily pertain to older and asymptomatic
      patients.

PMID- 18065504
TI  - Identification of the normal jugular foramen and lower cranial nerve anatomy:
      contrast-enhanced 3D fast imaging employing steady-state acquisition MR imaging.
AB  - SUMMARY: Conventional imaging protocols are unable to visualize the
      intraforaminal/canalicular segments of the lower cranial nerves (IX-XII). On the
      basis of previous successful demonstration of individual cranial nerves within
      the cavernous sinus by constructive interference in steady-state MR imaging, we
      describe the use of contrast-enhanced 3D fast imaging employing steady-state
      acquisition MR imaging to demonstrate normal in vivo intraforaminal and
      canalicular segments of cranial nerves IX-XII in 10 patients by using a
      standardized imaging protocol.

PMID- 18065505
TI  - Contrast extravasation on CT predicts mortality in primary intracerebral
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Recent studies of intracerebral hemorrhage (ICH)
      treatments have highlighted the need to identify reliable predictors of hematoma
      expansion. The goal of this study was to determine whether contrast extravasation
      on multisection CT angiography (CTA) and/or contrast-enhanced CT (CECT) of the
      brain is associated with hematoma expansion and increased mortality in patients
      with primary ICH. MATERIALS AND METHODS: All patients with primary ICH who
      underwent CTA and CECT, as well as follow-up noncontrast CT (NCCT) before
      discharge/death from January 1, 2003, to September 30, 2005, were retrospectively
      identified. One neuroradiologist reviewed admission and follow-up NCCT for
      hematoma size and growth. A second neuroradiologist independently reviewed CTA
      and CECT for active contrast extravasation. Univariate and multivariate logistic
      regression analyses were performed to evaluate the significance of clinical and
      radiologic variables in predicting 30-day mortality, designated as the primary
      outcome. Hematoma growth was considered as a secondary outcome. RESULTS: Of 56
      patients, contrast extravasation was seen in 17.9% of patients on initial CTA and
      in 23.2% of patients on initial CECT following CTA. Univariate analysis showed
      that the presence of extravasation on CT, large initial hematoma size (>30 mL),
      the presence of "swirl sign" on NCCT, the Glasgow Coma Scale and ICH scores, and
      international normalized ratio were associated with increased mortality. On
      multivariate analysis, only contrast extravasation on CT (P = .017) independently
      predicted mortality. Contrast extravasation on CT (P < .001) was also an
      independent predictor of hematoma growth on multivariate analysis. CONCLUSION:
      Active contrast extravasation on CT in patients with primary ICH independently
      predicts mortality and hematoma growth.

PMID- 18065506
TI  - Cortical blindness, transient and otherwise, associated with detachable coil
      embolization of intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Cortical visual loss is a rare complication of cerebral
      angiography without a definitive pathophysiology. Given the rapid increase in
      endovascular procedures used to treat cerebral aneurysms, we explored the
      prevalence of this complication and whether we could add to the understanding of
      this disorder. MATERIALS AND METHODS: We performed a retrospective review of all
      procedures performed with the same contrast agent and detachable coils for
      treatment of posterior circulation aneurysms by 1 endovascular surgery service
      from 1996 to 2006. All patients were evaluated before and after each procedure by
      a team that included a neuro-ophthalmologist. RESULTS: Of 137 intra-arterial
      treatment procedures performed for posterior circulation aneurysms, we identified
      4 patients with cerebral vision loss complications. During the same time period,
      >500 aneurysms of the anterior cerebral circulation were treated without this
      complication. The visual field loss was unilateral in 2 and bilateral in 2
      patients. Recovery was complete in 3 and almost normal in the fourth patient. The
      amount of contrast used and the duration of the procedure were similar among all
      patients. The 4 patients had no identified specific risk factors for developing
      procedure-associated occipital dysfunction, all 4 had undergone prior
      angiography, and 1 patient had undergone repeat coiling, without complication.
      CONCLUSION: The 2.9% prevalence of cerebral visual loss with endovascular coil
      treatment of posterior circulation aneurysms is higher than that for angiography
      alone. Our patients recovered well with corticosteroid and intravenous hydration
      treatment. Recognizing the self-limiting nature of this problem might prevent an
      unneeded intervention.

PMID- 18065507
TI  - Selective cerebral volume reduction in Rett syndrome: a multiple-approach MR
      imaging study.
AB  - BACKGROUND AND PURPOSE: Previous studies have examined volumetric abnormalities
      in Rett syndrome (RTT), using MR imaging and focusing on selective changes.
      However, these studies preceded the identification of MECP2 as the gene mutated
      in most RTT cases. We studied regional brain volume changes as noted by MR
      imaging in girls with RTT who had mutations in the MECP2 gene and more or less
      severe clinical outcomes to further characterize the neuroanatomy of RTT and its
      correlations with clinical severity. MATERIALS AND METHODS: Complementary
      semiautomated Talairach- and voxel-based approaches were used to study spoiled
      gradient-recalled acquisition sequence MR imaging scans from 23 girls with MECP2
      mutations/RTT, including a pair of discordant monozygotic twins and 25 age
      matched control girls. Both absolute and relative volumetric changes were
      examined to account for the well-documented global reduction in brain volume seen
      in RTT. RESULTS: Absolute volumetric reductions were observed throughout the
      brain in RTT. Selective/relative decreases in parietal lobe gray matter,
      particularly in the dorsal parietal region, and mild, diffuse reductions in
      cortical white matter were observed in the RTT group compared with control
      subjects. In girls with RTT and a more severe phenotype, anterior frontal lobe
      volumes were relatively more reduced. Twin comparisons revealed selective
      preservation of the occipital cortex. CONCLUSION: Selective reductions of dorsal
      parietal gray matter and preservation of the occipital cortex seem to be basic
      neuroanatomic features of RTT, whereas preferential reduction of the anterior
      frontal lobe appears to be a correlate of clinical severity in this disorder. The
      most affected brain regions include those that may underlie key functional
      deficits observed in RTT.

PMID- 18065508
TI  - A comparison of angiographic CT and multisection CT in lumbar myelographic
      imaging.
AB  - BACKGROUND AND PURPOSE: The purpose of this work was to provide an
      intraindividual comparison of angiographic CT (ACT) and multisection CT (MSCT) in
      lumbar myelographic imaging and to evaluate possible benefits of ACT, which is a
      further development of rotational angiography providing image data of high
      spatial and CT-like contrast resolution. MATERIALS AND METHODS: In 26 patients
      with degenerative lumbar spine disease a lumbar ACT was performed in combination
      with conventional lumbar myelography and followed by postmyelographic MSCT.
      Conventional lumbar myelography and lumbar ACT were performed with a flat panel
      detector-equipped angiographic device. Postmyelographic MSCT was performed with a
      16-section CT scanner. Three experienced neuroradiologists rated anonymized sets
      of multiplanar reformatted CT and ACT images regarding diagnostic and technical
      parameters. The ratings were repeated after 2 months. Weighted kappa statistics
      were calculated to describe the levels of intraobserver and interobserver
      agreement. RESULTS: The analysis shows that MSCT achieves higher ratings than ACT
      in all of the parameters asked. An adequate diagnostic quality was only assigned
      to 80% of the ACT acquisitions compared with 97% of the MSCT acquisitions. All of
      the mean kappa values were above 0.60, demonstrating a substantial intraobserver
      and interobserver agreement for MSCT, as well as for ACT. CONCLUSION: Using ACT,
      radiographic myelography and myelographic CT can be performed at the same imaging
      system. However, the results of our study show that the current myelographic ACT
      image quality fails to apply diagnostic standards. We, therefore, cannot
      recommend ACT as a general alternative to postmyelographic MSCT.

PMID- 18065509
TI  - Outcome after complicated minor head injury.
AB  - BACKGROUND AND PURPOSE: Functional outcome in patients with minor head injury
      with neurocranial traumatic findings on CT is largely unknown. We hypothesized
      that certain CT findings may be predictive of poor functional outcome. MATERIALS
      AND METHODS: All patients from the CT in Head Injury Patients (CHIP) study with
      neurocranial traumatic CT findings were included. The CHIP study is a
      prospective, multicenter study of consecutive patients, > or =16 years of age,
      presenting within 24 hours of blunt head injury, with a Glasgow Coma Scale (GCS)
      score of 13-14 or a GCS score of 15 and a risk factor. Primary outcome was
      functional outcome according to the Glasgow Outcome Scale (GOS). Other outcome
      measures were the modified Rankin Scale (mRS), the Barthel Index (BI), and number
      and severity of postconcussive symptoms. The association between CT findings and
      outcome was assessed by using univariable and multivariable regression analysis.
      RESULTS: GOS was assessed in 237/312 patients (76%) at an average of 15 months
      after injury. There was full recovery in 150 patients (63%), moderate disability
      in 70 (30%), severe disability in 7 (3.0%), and death in 10 (4.2%). Outcome
      according to the mRS and BI was also favorable in most patients, but 82% of
      patients had postconcussive symptoms. Evidence of parenchymal damage was the only
      independent predictor of poor functional outcome (odds ratio = 1.89, P = .022).
      CONCLUSION: Patients with neurocranial complications after minor head injury
      generally make a good functional recovery, but postconcussive symptoms may
      persist. Evidence of parenchymal damage on CT was predictive of poor functional
      outcome.

PMID- 18065510
TI  - Detection of aneurysms by 64-section multidetector CT angiography in patients
      acutely suspected of having an intracranial aneurysm and comparison with digital
      subtraction and 3D rotational angiography.
AB  - BACKGROUND AND PURPOSE: Four-section multisection CT angiography (MSCTA)
      accurately detects aneurysms at or more than 4 mm but is less accurate for those
      less than 4 mm. Our purpose was to determine the accuracy of 64-section MSCTA
      (64MSCTA) in aneurysm detection versus combined digital subtraction angiography
      (DSA) and 3D rotational angiography (3DRA). MATERIALS AND METHODS: In a
      retrospective review of patients studied because of acute symptoms suspicious for
      arising from an intracranial aneurysm, 63 subjects were included who had
      undergone CT angiography (CTA). Of these, 36 underwent catheter DSA; all but 4
      were also studied with 3DRA. The most common indication was subarachnoid
      hemorrhage (SAH; n = 43). Two neuroradiologists independently reviewed each CTA,
      DSA, and 3DRA. RESULTS: A total of 41 aneurysms were found in 28 patients. The
      mean size was 6.09 mm on DSA/3DRA and 5.98 mm on 64MSCTA. kappa was excellent
      (0.97) between the aneurysm size on 64MSCTA and DSA/3DRA. Ultimately, 37
      aneurysms were detected by DSA/3DRA in 25 of the 36 patients who underwent
      conventional angiography. The reviewers noted four 1- to 1.5-mm sessile
      outpouchings only on 3DRA; none were considered a source of SAH. One 64MSCTA was
      false positive, whereas one 2-mm aneurysm was missed by CTA. The sensitivity of
      CTA for aneurysms less than 4 mm was 92.3%, whereas it was 100% for those 4-10 mm
      and more than 10 mm, excluding the indeterminate, sessile lesions. CONCLUSIONS:
      In comparison with the available literature, 64MSCTA may have improved the
      detection of less than 4-mm aneurysms compared with 4- or 16-section CTA.
      However, the combination of DSA with 3DRA is currently the most sensitive
      technique to detect untreated aneurysms and should be considered in suspicious
      cases of SAH where the aneurysm is not depicted by 64MSCTA, because 64MSCTA may
      occasionally miss aneurysms less than 3-4 mm size.

PMID- 18065511
TI  - Dynamic enhancement features of cavernous sinus cavernous hemangiomas on
      conventional contrast-enhanced MR imaging.
AB  - BACKGROUND AND PURPOSE: The reported MR imaging characteristics of cavernous
      sinus cavernous hemangiomas (CSCHs) in the literature are nonspecific. The
      purpose of our study was to explore dynamic enhancement features of CSCHs on
      conventional contrast-enhanced MR imaging and to correlate these features with
      histopathologic subtypes. MATERIALS AND METHODS: Twenty-one patients (8 male and
      13 female; age range, 13-63 years; average age, 42.6 years) with surgically
      confirmed CSCHs were retrospectively investigated. Preoperative MR study was
      performed in all cases, consisting of T1-weighted axial imaging, T2-weighted
      axial imaging, T1-weighted sagittal imaging, and contrast-enhanced T1-weighted
      axial, sagittal, and coronal images. RESULTS: There were 4.8% (1/21) that showed
      homogeneous enhancement on all 3 contrast-enhanced sequences, whereas 95.2%
      (20/21) demonstrated heterogeneous enhancement on the first contrast-enhanced
      sequence. Among the 20 lesions, on subsequent contrast-enhanced sequences, 55.0%
      (11/20) showed homogeneous enhancement, whereas 35.0% (7/20) of lesions showed
      progressive contrast "filling in." The remaining 10% (2/20) exhibited no apparent
      enhancement changes. The 95.2% (20/21) of lesions with heterogeneous enhancement
      on the first contrast-enhanced sequence correlated with type B or type C
      pathologic findings, whereas 4.8% (1/21) with homogeneous enhancement correlated
      with type A pathologic findings. Among the 20 type B or type C lesions, 80%
      (16/20) achieved total or near-total resection. CONCLUSION: Progressive contrast
      "filling in" in the tumors on conventional contrast-enhanced MR images can aid in
      differentiating between cavernous sinus lesions and suggest the diagnosis of
      cavernous hemangiomas.

PMID- 18065512
TI  - High b-value diffusion (b = 3000 s/mm2) MR imaging in cerebral gliomas at 3T:
      visual and quantitative comparisons with b = 1000 s/mm2.
AB  - BACKGROUND AND PURPOSE: High b-value diffusion-weighted imaging (DWI) provides
      different features not appreciated at lower b-value and have been recently
      studied in several clinical issues. The purpose of this study was to assess
      whether DWI at b = 3000 s/mm(2) is more useful in discriminating high-grade and
      low-grade gliomas than DWI at b = 1000 s/mm(2) at 3T. MATERIALS AND METHODS: DWIs
      at both b = 1000 and 3000 s/mm(2) were performed at 3T in 62 patients, 49 high
      grade gliomas (20 World Health Organization [WHO] grade III and 29 grade IV) and
      13 low-grade gliomas (13 grade II). Visual assessments based on 5-point scaled
      evaluations, receiver operating characteristic (ROC) curve analysis, and
      quantitative assessment based on DWI signal intensity (SI) ratio (tumor SI/normal
      SI) and apparent diffusion coefficient (ADC) values were compared between DWIs at
      b = 1000 and 3000 s/mm(2). RESULTS: By visual assessment, DWI at b = 3000 s/mm(2)
      showed more conspicuous hyperintensity in high-grade gliomas and hypointensity in
      low-grade gliomas than DWI at b = 1000 s/mm(2). Sensitivity and specificity at b
      = 3000 s/mm(2) were higher than at b = 1000 s/mm(2) (83.7%, 84.6% vs 69.4%,
      76.9%, respectively). Quantitative assessments showed that mean SI ratio of high
      grade gliomas was significantly higher than that of low-grade gliomas at both b
      values. The mean ADC value of high-grade gliomas was significantly lower than
      that of low-grade gliomas at both b-values. The difference between the SI ratios
      of high-grade and low-grade gliomas was significantly larger at b = 3000 s/mm(2)
      than at b = 1000 s/mm(2). CONCLUSION: DWI at b = 3000 s/mm(2) is more useful than
      DWI at b = 1000 s/mm(2) in terms of discriminating high-grade and low-grade
      gliomas at 3T.

PMID- 18065513
TI  - Nearly completely reversible brain abnormalities in a patient with incontinentia
      pigmenti.
AB  - SUMMARY: We report a case of incontinentia pigmenti with reversible cortex and
      subcortical white matter necrosis-like presentation by MR imaging. The reversible
      changes in follow-up imaging of the patient with incontinentia pigmenti suggest a
      course of natural repair of inflammation or cerebrovascular disease.

PMID- 18065514
TI  - Temporal bone CT findings in Cornelia de Lange syndrome.
AB  - BACKGROUND AND PURPOSE: Cornelia de Lange syndrome is a rare developmental
      malformation syndrome with a high prevalence of hearing impairment. The purposes
      of this study were to describe the characteristic temporal bone CT findings in
      patients with Cornelia de Lange syndrome and to correlate audiometric data with
      radiologic findings in these patients. MATERIALS AND METHODS: Ten children (6
      girls and 4 boys; mean age, 42.0 months) who were clinically diagnosed with
      Cornelia de Lange syndrome (classic, n = 5; mild form, n = 5) were enrolled.
      Temporal bone CT was prospectively performed, and 32 aspects of each temporal
      bone CT were analyzed, 21 by direct measurement and 11 by visual inspection.
      Twenty age-matched children (n = 20 ears) with normal temporal bone CT scans
      served as a control group. Audiologic tests were also performed on all patients.
      RESULTS: Characteristic temporal bone CT findings of Cornelia de Lange syndrome
      were external auditory canal stenosis, soft-tissue opacification of the
      hypoplastic tympanomastoid cavity, dysmorphic ossicle, hypoplastic cochlea, and
      dysplastic vestibule, all of which were more prevalent in patients with the
      classic form of the disease than in those with the mild form. Children who had
      more severe structural abnormalities on temporal bone CT had worse hearing levels
      compared with those without structural abnormalities. CONCLUSION: Temporal bone
      CT scans in Cornelia de Lange syndrome could document combined structural
      abnormalities of the external, middle, and inner ear, which were one of the
      characteristic clinical manifestations; CT abnormalities were well correlated
      with the audiometric data.

PMID- 18065515
TI  - Pontine hypoplasia in children with periventricular leukomalacia.
AB  - BACKGROUND AND PURPOSE: The brain stem in patients with periventricular
      leukomalacia (PVL) appears smaller than normal on MR imaging, but few reports
      have described this feature, and the number of patients has been relatively
      small. The present study was conducted to examine the hypothesis that the pons in
      patients with PVL is smaller than normal. MATERIALS AND METHODS: Using MR
      imaging, we examined 80 children (43 boys and 37 girls) with PVL and 80 age
      matched control children (41 boys and 39 girls). The control children were
      diagnosed as neurologically and developmentally normal by pediatric neurologists
      and also showed normal MR imaging findings. MR imaging was performed at a
      corrected age range of 0-5 years in both groups. We measured the anteroposterior
      diameter of the whole pons, the tegmentum and the basis, and the corpus callosal
      length by using midline T1-weighted sagittal images and compared each parameter
      between the PVL groups and the control groups. RESULTS: Pontine diameters in all
      of the regions were significantly smaller in the PVL group than in the control
      group (mean +/- SD, whole pontine diameters, 1.66 +/- 0.21 and 1.87 +/- 0.23 cm
      [P < .001]; basis diameters, 0.42 +/- 0.10 and 0.51 +/- 0.14 [P < .001];
      tegmentum diameters, 1.23 +/- 0.20 and 1.36 +/- 0.19 [P < .001], respectively).
      The respective corpus callosal lengths were 5.02 +/- 0.90 and 5.51 +/- 0.76 (P <
      .001). There was no significant difference in the basis/tegmentum ratio between
      the PVL group and the control group. When the age-related pontine diameter
      differences were examined, there was already a significant difference at 0 years
      of age between the 2 groups. There was a significant correlation between whole
      pontine diameter and corpus callosal length in the PVL group (correlation
      coefficient, 0.52; P < .001) and the control group (correlation coefficient,
      0.63; P < .001). CONCLUSION: We have proven that pontine diameter in patients
      with PVL is significantly smaller than that in normal control subjects, including
      each diameter of basis and tegmentum.

PMID- 18065516
TI  - Primary cerebral lymphoma and glioblastoma multiforme: differences in diffusion
      characteristics evaluated with diffusion tensor imaging.
AB  - BACKGROUND AND PURPOSE: Differentiating between primary cerebral lymphoma and
      glioblastoma multiforme (GBM) based on conventional MR imaging sequences may be
      impossible. Our hypothesis was that there are significant differences in
      fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between
      lymphoma and GBM, which will allow for differentiation between them. MATERIALS
      AND METHODS: Preoperative diffusion tensor imaging (DTI) was performed in 10
      patients with lymphoma and 10 patients with GBM. Regions of interest were placed
      in only solid-enhancing tumor areas and the contralateral normal-appearing white
      matter (NAWM) to measure the FA and ADC values. The differences in FA and ADC
      between lymphoma and GBM, as well as between solid-enhancing areas of each tumor
      type and contralateral NAWM, were analyzed statistically. Cutoff values of FA, FA
      ratio, ADC, and ADC ratio for distinguishing lymphomas from GBMs were determined
      by receiver operating characteristic curve analysis. RESULTS: FA and ADC values
      of lymphoma were significantly decreased compared with NAWM. Mean FA, FA ratio,
      ADC (x10(-3) mm(2)/s), and ADC ratios were 0.140 +/- 0.024, 0.25 +/- 0.04, 0.630
      +/- 0.155, and 0.83 +/- 0.14 for lymphoma, respectively, and 0.229 +/- 0.069,
      0.40 +/- 0.12, 0.963 +/- 0.119, and 1.26 +/- 0.13 for GBM, respectively. All of
      the values were significantly different between lymphomas and GBM. Cutoff values
      to differentiate lymphomas from GBM were 0.192 for FA, 0.33 for FA ratio, 0.818
      for ADC, and 1.06 for ADC ratio. CONCLUSIONS: The FA and ADC of primary cerebral
      lymphoma were significantly lower than those of GBM. DTI is able to differentiate
      lymphomas from GBM.

PMID- 18065517
TI  - Therapeutic potential of peroxisome proliferators--activated receptor-alpha/gamma
      dual agonist with alleviation of endoplasmic reticulum stress for the treatment
      of diabetes.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual
      agonists have the potential to be used as therapeutic agents for the treatment of
      type 2 diabetes. This study evaluated the function of macelignan, a natural
      compound isolated from Myristica fragrans, as a dual agonist for PPARalpha/gamma
      and investigated its antidiabetes effects in animal models. RESEARCH DESIGN AND
      METHODS: GAL4/PPAR chimera transactivation was performed and the expression of
      PPARalpha/gamma target genes was monitored to examine the ability of macelignan
      to activate PPARalpha/gamma. Additionally, macelignan was administrated to obese
      diabetic (db/db) mice to investigate antidiabetes effects and elucidate its
      molecular mechanisms. RESULTS: Macelignan reduced serum glucose, insulin,
      triglycerides, free fatty acid levels, and triglycerides levels in the skeletal
      muscle and liver of db/db mice. Furthermore, macelignan significantly improved
      glucose and insulin tolerance in these mice, and without altering food intake,
      their body weights were slightly reduced while weights of troglitazone-treated
      mice increased. Macelignan increased adiponectin expression in adipose tissue and
      serum, whereas the expression and serum levels of tumor necrosis factor-alpha and
      interleukin-6 decreased. Macelignan downregulated inflammatory gene expression in
      the liver and increased AMP-activated protein kinase activation in the skeletal
      muscle of db/db mice. Strikingly, macelignan reduced endoplasmic reticulum (ER)
      stress and c-Jun NH(2)-terminal kinase activation in the liver and adipose tissue
      of db/db mice and subsequently increased insulin signaling. CONCLUSIONS:
      Macelignan enhanced insulin sensitivity and improved lipid metabolic disorders by
      activating PPARalpha/gamma and attenuating ER stress, suggesting that it has
      potential as an antidiabetes agent for the treatment of type 2 diabetes.

PMID- 18065518
TI  - Analysis of single nucleotide polymorphisms identifies major type 1A diabetes
      locus telomeric of the major histocompatibility complex.
AB  - OBJECTIVE: HLA-DRB1*03-DQB1*0201/DRB1*04-DQB1*0302 (DR3/4-DQ8) siblings who share
      both major histocompatibility complex (MHC) haplotypes identical-by-descent with
      their proband siblings have a higher risk for type 1A diabetes than DR3/4-DQ8
      siblings who do not share both MHC haplotypes identical-by-descent. Our goal was
      to search for non-DR/DQ MHC genetic determinants that cause the additional risk
      in the DR3/4-DQ8 siblings who share both MHC haplotypes. RESEARCH DESIGN AND
      METHODS: We completed an extensive single nucleotide polymorphism (SNP) analysis
      of the extended MHC in 237 families with type 1A diabetes from the U.S. and 1,240
      families from the Type 1 Diabetes Genetics Consortium. RESULTS: We found evidence
      for an association with type 1A diabetes (rs1233478, P = 1.6 x 10(-23), allelic
      odds ratio 2.0) in the UBD/MAS1L region, telomeric of the classic MHC. We also
      observed over 99% conservation for up to 9 million nucleotides between
      chromosomes containing a common haplotype with the HLA-DRB1*03, HLA-B*08, and HLA
      A*01 alleles, termed the "8.1 haplotype." The diabetes association in the
      UBD/MAS1L region remained significant both after chromosomes with the 8.1
      haplotype were removed (rs1233478, P = 1.4 x 10(-12)) and after adjustment for
      known HLA risk factors HLA-DRB1, HLA-DQB1, HLA-B, and HLA-A (P = 0.01).
      CONCLUSIONS: Polymorphisms in the region of the UBD/MAS1L genes are associated
      with type 1A diabetes independent of HLA class II and I alleles.

PMID- 18065519
TI  - Reduced immunogenicity of first-trimester human fetal pancreas.
AB  - OBJECTIVE: The use of human fetal pancreatic tissue may provide a potential
      source of transplantable beta-cells as a therapy for type 1 diabetes. Human fetal
      pancreas has a remarkable capacity to grow and differentiate in vivo and has been
      shown to reverse diabetes in rodents. However, it is known that human fetal
      pancreas obtained from the second trimester of gestation is immunogenic and is
      rejected after transplantation. Tissue obtained from earlier stages might prove
      to be immune privileged, as has been shown for other tissues. RESEARCH DESIGN AND
      METHODS: In this study, we determined the immunogenicity of human fetal
      pancreatic tissue obtained from the first trimester of gestation in a humanized
      mouse model. A microarray study of immunoregulatory gene expression in first- and
      second-trimester human fetal pancreas was also undertaken. RESULTS: The analysis
      of transplanted human fetal pancreata revealed a significantly decreased
      immunogenicity of the first-trimester tissue. The first-trimester grafts showed
      only limited cellular infiltration and contained numerous insulin-positive cells,
      whereas second-trimester tissue was completely infiltrated and rejected.
      Furthermore an analysis of immunoregulatory genes expressed in first- and second
      trimester human fetal pancreas by microarray demonstrated the upregulation of
      several key immunoregulatory genes in the second-trimester tissue. This might
      account for the reduced immunogenicity of the younger tissue. CONCLUSIONS: Our
      results provide the first indication that the use of first-trimester human fetal
      pancreas for transplantation might increase the survival of the grafts and might
      decrease the requirement for immunosuppressive drugs.

PMID- 18065520
TI  - Resistin impairs insulin-evoked vasodilation.
AB  - OBJECTIVE: Since vascular dysfunction is a main trait of obese subjects, in the
      present study we evaluated the vascular impact of resistin, a recently discovered
      hormone markedly increased in obesity. RESEARCH DESIGN AND METHODS: We performed
      our analysis on aortic and mesenteric segments from young and old C57BL/6 mice
      and on cultured endothelial cells. Resistin-induced vascular effect was evaluated
      in vitro and in vivo. Molecular analyses were performed by immunoprecipitation
      and Western blotting. RESULTS: Recombinant murine resistin did not induce changes
      in either basal vascular tone or phenylephrine-induced vascular contraction. In
      contrast, both in vivo and in vitro administration of resistin significantly
      impaired dose-dependent insulin-evoked vasodilation by reducing endothelial
      nitric oxide synthase (eNOS) enzymatic activity. This effect of resistin was
      selective for insulin vascular action, since vasodilatation induced by increasing
      doses of acetylcholine or nitroglycerin was not influenced by the hormone.
      Molecular analysis of endothelial cells further detailed resistin-induced
      vascular resistance by showing impairment of insulin-evoked AKT and eNOS
      phosphorylations after exposure to resistin. Even this latter abnormality is
      selective of insulin signaling since AKT/eNOS phosphorylations are normally
      activated during acetylcholine stimulation. More important, the resistin-induced
      endothelial dysfunction depends on resistin's ability to alter insulin receptor
      substrate (IRS)-1 tyrosine/serine phosphorylation and its consequent interaction
      with phosphatidylinositol 3-kinase. CONCLUSIONS: Our results demonstrate that
      resistin is able to induce a selective vascular insulin resistance-impairing
      endothelial IRS-1 signaling pathway that leads to eNOS activation and
      vasodilation.

PMID- 18065521
TI  - SOX-18 controls endothelial-specific claudin-5 gene expression and barrier
      function.
AB  - Members of the claudin family constitute tight junction strands and are major
      determinants in specificity and selectivity of paracellular barriers.
      Transcriptional control of claudin gene expression is essential to establish
      individual claudin expression patterns and barrier properties. Using full genome
      expression profiling, we now identify sex-determining region Y-box (SOX)-18, a
      member of the SOX family of high-mobility group box transcription factors, as one
      of the most differentially induced genes during establishment of the endothelial
      barrier. We show that overexpression of SOX-18 and a dominant-negative mutant
      thereof, as well as SOX-18 silencing, greatly affect levels of claudin-5 (CLDN5).
      The relevance of an evolutionary conserved SOX-binding site in the CLDN5 promoter
      is shown using sequential promoter deletions, as well as point mutations.
      Furthermore, SOX-18 silencing abrogates endothelial barrier function, as measured
      by electric cell-substrate impedance sensing. Thus an obligatory role for SOX-18
      in the regulation of CLDN5 gene expression in an endothelial-specific and cell
      density-dependent manner is established, as well as a crucial, nonredundant role
      for specifically SOX-18 in the formation of the endothelial barrier.

PMID- 18065522
TI  - Altered expression of connexin43 contributes to the arrhythmogenic substrate
      during the development of heart failure in cardiomyopathic hamster.
AB  - Heart failure is known to predispose to life-threatening ventricular
      tachyarrhythmias even before compromising the systemic circulation, but the
      underlying mechanism is not well understood. The aim of this study was to clarify
      the connexin43 (Cx43) gap junction remodeling and its potential role in the
      pathogenesis of arrhythmias during the development of heart failure. We
      investigated stage-dependent changes in Cx43 expression in UM-X7.1
      cardiomyopathic hamster hearts and associated alterations in the
      electrophysiological properties using a high-resolution optical mapping system.
      UM-X7.1 hamsters developed left ventricular (LV) hypertrophy by ages 6
      approximately 10 wk and showed a moderate reduction in LV contractility at age 20
      wk. Appreciable interstitial fibrosis was recognized at these stages. LV mRNA and
      protein levels of Cx43 in UM-X7.1 were unaffected at age 10 wk but significantly
      reduced at 20 wk. The expression level of Ser255-phosphorylated Cx43 in UM-X7.1
      at age 20 wk was significantly greater than that in control golden hamsters at
      the same age. In UM-X7.1 at age 10 wk, almost normal LV conduction was preserved,
      whereas the dispersion of action potential duration was significantly increased.
      UM-X7.1 at age 20 wk showed significant reduction of cardiac space constant,
      significant decrease in conduction velocity, marked distortion of activation
      fronts, and pronounced increase in action potential duration dispersion.
      Programmed stimulation resulted in sustained ventricular tachycardia or
      fibrillation in UM-X7.1. LV activation during polymorphic ventricular tachycardia
      was characterized by multiple phase singularities or wavebreaks. During the
      development of heart failure in the cardiomyopathic hamster, alterations of Cx43
      expression and phosphorylation in concert with interstitial fibrosis may create
      serious arrhythmogenic substrate through an inhibition of cell-to-cell coupling.

PMID- 18065523
TI  - Interruption of endothelin signaling modifies membrane type 1 matrix
      metalloproteinase activity during ischemia and reperfusion.
AB  - The matrix metalloproteinases (MMPs), in particular, membrane type 1 MMP (MT1
      MMP), are increased in the context of myocardial ischemia and reperfusion (I/R)
      and likely contribute to myocardial dysfunction. One potential upstream induction
      mechanism for MT1-MMP is endothelin (ET) release and subsequent protein kinase C
      (PKC) activation. Modulation of ET and PKC signaling with respect to MT1-MMP
      activity with I/R has yet to be explored. Accordingly, this study examined in
      vivo MT1-MMP activation during I/R following modification of ET signaling and PKC
      activation. With the use of a novel fluorogenic microdialysis system, myocardial
      interstitial MT1-MMP activity was measured in pigs (30 kg; n = 9) during I/R (90
      min I/120 min R). Local ET(A) receptor antagonism (BQ-123, 1 microM) and PKC
      inhibition (chelerythrine, 1 microM) were performed in parallel microdialysis
      probes. MT1-MMP activity was increased during I/R by 122 +/- 10% (P < 0.05) and
      was unchanged from baseline with ET antagonism and/or PKC inhibition. Selective
      PKC isoform induction occurred such that PKC-betaII increased by 198 +/- 31% (P <
      0.05). MT1-MMP phosphothreonine, a putative PKC phosphorylation site, was
      increased by 121 +/- 8% (P < 0.05) in the I/R region. These studies demonstrate
      for the first time that increased interstitial MT1-MMP activity during I/R is a
      result of the ET/PKC pathway and may be due to enhanced phosphorylation of MT1
      MMP. These findings identify multiple potential targets for modulating a local
      proteolytic pathway operative during I/R.

PMID- 18065524
TI  - Cardiac autonomic balance in small-for-gestational-age neonates.
AB  - The cardiac sympathetic nervous system is one putative key factor involved in the
      intrauterine programming of adult cardiovascular disease. We therefore analyzed
      cardiac autonomic system activity in small for gestational age (SGA) neonates.
      Heart rate variability (HRV) from 24-h ECG recordings were analyzed for time
      domain and frequency-domain parameters in 27 SGA neonates [median 261 (240-283)
      days of gestation] compared with 27 appropriate for gestational age (AGA)
      neonates [median 270 (239-293) days of gestation]. In addition, salivary alpha
      amylase levels were analyzed during resting conditions and in response to a pain
      induced stress event in 18 SGA [median 266 (240-292) days of gestation] and 34
      AGA [median 271 (240-294) days of gestation] neonates. Overall HRV was not
      significantly different in SGA neonates compared with AGA neonates (SD of all
      valid NN intervals: P = 0.14; triangular index: P = 0.29), and the sympathovagal
      balance [low frequency (LF)/high frequency (HF)] was similar (P = 0.62).
      Parameters mostly influenced by sympathetic activity did not reveal significant
      differences: (SD of the average of valid NN intervals: P = 0.27; average of the
      hourly means of SDs of all NN intervals: P = 0.66, LF: P = 0.83) as well as vagal
      tone-influenced parameters were unaltered (average of the hourly square root of
      the mean of the sum of the squares of differences between adjacent NN intervals:
      P = 0.59; proportion of pairs of adjacent NN intervals differing by >50 ms: P =
      0.93; HF: P = 0.82). Median resting levels for alpha-amylase were not
      significantly different in SGA neonates (P = 0.13), and a neonatal stress
      stimulus revealed similar stress response patterns (P = 0.29). HRV and salivary
      alpha-amylase levels as indicators of cardiac autonomic activity were not altered
      in SGA neonates compared with AGA neonates. Thus, it appears that the
      intrauterine activation of the sympathetic system in SGA fetuses does not
      directly persist into postnatal life, and neonatal sympathovagal balance appears
      to be preserved.

PMID- 18065525
TI  - Why, where, and when do cardiac myocytes express inositol 1,4,5-trisphosphate
      receptors?

PMID- 18065526
TI  - Characterization of the phospholemman knockout mouse heart: depressed left
      ventricular function with increased Na-K-ATPase activity.
AB  - Phospholemman (PLM, FXYD1), abundantly expressed in the heart, is the primary
      cardiac sarcolemmal substrate for PKA and PKC. Evidence supports the hypothesis
      that PLM is part of the cardiac Na-K pump complex and provides the link between
      kinase activity and pump modulation. PLM has also been proposed to modulate Na/Ca
      exchanger activity and may be involved in cell volume regulation. This study
      characterized the phenotype of the PLM knockout (KO) mouse heart to further our
      understanding of PLM function in the heart. PLM KO mice were bred on a congenic
      C57/BL6 background. In vivo conductance catheter measurements exhibited a mildly
      depressed cardiac contractile function in PLM KO mice, which was exacerbated when
      hearts were isolated and Langendorff perfused. There were no significant
      differences in action potential morphology in paced Langendorff-perfused hearts.
      Depressed contractile function was associated with a mild cardiac hypertrophy in
      PLM KO mice. Biochemical analysis of crude ventricular homogenates showed a
      significant increase in Na-K-ATPase activity in PLM KO hearts compared with wild
      type controls. SDS-PAGE and Western blot analysis of ventricular homogenates
      revealed small, nonsignificant changes in Na- K-ATPase subunit expression, with
      two-dimensional gel (isoelectric focusing, SDS-PAGE) analysis revealing minimal
      changes in ventricular protein expression, indicating that deletion of PLM was
      the primary reason for the observed PLM KO phenotype. These studies demonstrate
      that PLM plays an important role in the contractile function of the normoxic
      mouse heart. Data are consistent with the hypothesis that PLM modulates Na-K
      ATPase activity, indirectly affecting intracellular Ca and hence contractile
      function.

PMID- 18065527
TI  - Protective mechanisms of resveratrol against ischemia-reperfusion-induced damage
      in hearts obtained from Zucker obese rats: the role of GLUT-4 and endothelin.
AB  - The resveratrol-induced cardiac protection was studied in Zucker obese rats. Rats
      were divided into five groups: group 1, lean control; group 2, obese control
      (OC); group 3, obese rats treated orally with 5 mg kg(-1) day(-1) of resveratrol
      (OR) for 2 wk; group 4, obese rats received 10% glucose solution ad libitum for 3
      wk (OG); and group 5, obese rats received 10% glucose for 3 wk and resveratrol
      (OGR) during the 2nd and 3rd wk. Body weight, serum glucose, and insulin were
      measured, and then hearts were isolated and subjected to 30 min of ischemia
      followed by 120 min of reperfusion. Heart rate, coronary flow, aortic flow,
      developed pressure, the incidence of reperfusion-induced ventricular
      fibrillation, and infarct size were measured. Resveratrol reduced body weight and
      serum glucose in the OR compared with the OC values (414 +/- 10 g and 7.08 +/-
      0.41 mmol/l, respectively, to 378 +/- 12 g and 6.11 +/- 0.44 mmol/l), but insulin
      levels were unchanged. The same results were obtained for the OG vs. OGR group.
      Resveratrol improved postischemic cardiac function in the presence or absence of
      glucose intake compared with the resveratrol-free group. The incidence of
      ventricular fibrillation and infarct size was reduced by 83 and 20% in the OR
      group, and 67 and 16% in the OGR group, compared with the OC and OG groups,
      respectively. Resveratrol increased GLUT-4 expression and reduced endothelin
      expression and cardiac apoptosis in ischemic-reperfused hearts in the presence or
      absence of glucose intake. Thus the protective effect of resveratrol could be
      related to its direct effects on the heart.

PMID- 18065528
TI  - Additional in vitro and in vivo evidence for SecA functioning as dimers in the
      membrane: dissociation into monomers is not essential for protein translocation
      in Escherichia coli.
AB  - SecA is an essential component in the Sec-dependent protein translocation pathway
      and, together with ATP, provides the driving force for the transport of secretory
      proteins across the cytoplasmic membrane of Escherichia coli. Previous studies
      established that SecA undergoes monomer-dimer equilibrium in solution. However,
      the oligomeric state of functional SecA during the protein translocation process
      is controversial. In this study, we provide additional evidence that SecA
      functions as a dimer in the membrane by (i) demonstration of the capability of
      the presumably monomeric SecA derivative to be cross-linked as dimers in vitro
      and in vivo, (ii) complementation of the growth of a secA(Ts) mutant with another
      nonfunctional SecA or (iii) in vivo complementation and in vitro function of a
      genetically tandem SecA dimer that does not dissociate into monomers, and (iv)
      formation of similar ring-like structures by the tandem SecA dimer and SecA in
      the presence of lipid bilayers. We conclude that SecA functions as a dimer in the
      membrane and dissociation into monomers is not necessary during protein
      translocation.

PMID- 18065530
TI  - A transposase-independent mechanism gives rise to precise excision of IS256 from
      insertion sites in Staphylococcus epidermidis.
AB  - The mobile element IS256 causes phase variation of biofilm formation in
      Staphylococcus epidermidis by insertion and precise excision from the icaADBC
      operon. Precise excision, i.e., removal of the target site duplications (TSDs)
      and restoration of the original DNA sequence, occurs rarely but independently of
      functional transposase. Instead, the integrity of the TSDs is crucial for precise
      excision. Excision increased significantly when the TSDs were brought into closer
      spatial proximity, suggesting that excision is a host-driven process that might
      involve most likely illegitimate recombination.

PMID- 18065529
TI  - Structure of [NiFe] hydrogenase maturation protein HypE from Escherichia coli and
      its interaction with HypF.
AB  - Hydrogenases are enzymes involved in hydrogen metabolism, utilizing H2 as an
      electron source. [NiFe] hydrogenases are heterodimeric Fe-S proteins, with a
      large subunit containing the reaction center involving Fe and Ni metal ions and a
      small subunit containing one or more Fe-S clusters. Maturation of the [NiFe]
      hydrogenase involves assembly of nonproteinaceous ligands on the large subunit by
      accessory proteins encoded by the hyp operon. HypE is an essential accessory
      protein and participates in the synthesis of two cyano groups found in the large
      subunit. We report the crystal structure of Escherichia coli HypE at 2.0-A
      resolution. HypE exhibits a fold similar to that of PurM and ThiL and forms
      dimers. The C-terminal catalytically essential Cys336 is internalized at the
      dimer interface between the N- and C-terminal domains. A mechanism for
      dehydration of the thiocarbamate to the thiocyanate is proposed, involving Asp83
      and Glu272. The interactions of HypE and HypF were characterized in detail by
      surface plasmon resonance and isothermal titration calorimetry, revealing a Kd
      (dissociation constant) of approximately 400 nM. The stoichiometry and molecular
      weights of the complex were verified by size exclusion chromatography and gel
      scanning densitometry. These experiments reveal that HypE and HypF associate to
      form a stoichiometric, hetero-oligomeric complex predominantly consisting of a
      [EF]2 heterotetramer which exists in a dynamic equilibrium with the EF
      heterodimer. The surface plasmon resonance results indicate that a conformational
      change occurs upon heterodimerization which facilitates formation of a productive
      complex as part of the carbamate transfer reaction.

PMID- 18065531
TI  - The Campylobacter jejuni NADH:ubiquinone oxidoreductase (complex I) utilizes
      flavodoxin rather than NADH.
AB  - Campylobacter jejuni encodes 12 of the 14 subunits that make up the respiratory
      enzyme NADH:ubiquinone oxidoreductase (also called complex I). The two nuo genes
      not present in C. jejuni encode the NADH dehydrogenase, and in their place in the
      operon are the novel genes designated Cj1575c and Cj1574c. A series of mutants
      was generated in which each of the 12 nuo genes (homologues to known complex I
      subunits) was disrupted or deleted. Each of the nuo mutants will not grow in
      amino acid-based medium unless supplemented with an alternative respiratory
      substrate such as formate. Unlike the nuo genes, Cj1574c is an essential gene and
      could not be disrupted unless an intact copy of the gene was provided at an
      unrelated site on the chromosome. A nuo deletion mutant can efficiently respire
      formate but is deficient in alpha-ketoglutarate respiratory activity compared to
      the wild type. In C. jejuni, alpha-ketoglutarate respiration is mediated by the
      enzyme 2-oxoglutarate:acceptor oxidoreductase; mutagenesis of this enzyme
      abolishes alpha-ketoglutarate-dependent O2 uptake and fails to reduce the
      electron transport chain. The electron acceptor for 2-oxoglutarate:acceptor
      oxidoreductase was determined to be flavodoxin, which was also determined to be
      an essential protein in C. jejuni. A model is presented in which CJ1574 mediates
      electron flow into the respiratory transport chain from reduced flavodoxin and
      through complex I.

PMID- 18065532
TI  - The genome and structural proteome of YuA, a new Pseudomonas aeruginosa phage
      resembling M6.
AB  - Pseudomonas aeruginosa phage YuA (Siphoviridae) was isolated from a pond near
      Moscow, Russia. It has an elongated head, encapsulating a circularly permuted
      genome of 58,663 bp, and a flexible, noncontractile tail, which is terminally and
      subterminally decorated with short fibers. The YuA genome is neither Mu- nor
      lambda-like and encodes 78 gene products that cluster in three major regions
      involved in (i) DNA metabolism and replication, (ii) host interaction, and (iii)
      phage particle formation and host lysis. At the protein level, YuA displays
      significant homology with phages M6, phiJL001, 73, B3, DMS3, and D3112. Eighteen
      YuA proteins were identified as part of the phage particle by mass spectrometry
      analysis. Five different bacterial promoters were experimentally identified using
      a promoter trap assay, three of which have a sigma54-specific binding site and
      regulate transcription in the genome region involved in phage particle formation
      and host lysis. The dependency of these promoters on the host sigma54 factor was
      confirmed by analysis of an rpoN mutant strain of P. aeruginosa PAO1. At the DNA
      level, YuA is 91% identical to the recently (July 2007) annotated phage M6 of the
      Lindberg typing set. Despite this level of DNA homology throughout the genome,
      both phages combined have 15 unique genes that do not occur in the other phage.
      The genome organization of both phages differs substantially from those of the
      other known Pseudomonas-infecting Siphoviridae, delineating them as a distinct
      genus within this family.

PMID- 18065534
TI  - The complete genome sequence of Actinobacillus pleuropneumoniae L20 (serotype
      5b).
AB  - There are 16 capsule-based serotypes of Actinobacillus pleuropneumoniae, all of
      which are capable of causing disease in pigs. Here we report the finished and
      annotated genome sequence of the reference serotype 5b strain L20. This strain
      has a rough appearance and readily forms biofilms, as is typical for most field
      isolates.

PMID- 18065533
TI  - Interplay of different transporters in the mediation of divalent heavy metal
      resistance in Pseudomonas putida KT2440.
AB  - According to in silico analysis, the genome of Pseudomonas putida KT2440 encodes
      at least four Zn/Cd/Pb efflux transporters-two P-type ATPases (CadA1 and CadA2)
      and two czc chemiosmotic transporters (CzcCBA1 and CzcCBA2). In this study we
      showed that all these transporters are functional, but under laboratory
      conditions only two of them were involved in the mediation of heavy metal
      resistance in P. putida KT2440. CadA2 conferred Cd(2+) and Pb(2+) resistance,
      whereas CzcCBA1 was involved in export of Zn(2+), Cd(2+), and possibly Pb(2+).
      CadA1, although nonfunctional in P. putida, improved Zn(2+) resistance and
      slightly improved Cd(2+) resistance when it was expressed in Escherichia coli.
      CzcCBA2 contributed to Zn resistance of a czcA1-defective P. putida strain or
      when the CzcA2 subunit was overexpressed in a transporter-deficient strain. It
      seemed that CzcA2 could complex with CzcC1 and CzcB1 subunits and therefore
      complement the loss of CzcA1. The CzcCBA2 transporter itself, however, did not
      function. Expression of cadA1, cadA2, and czcCBA1 was induced by heavy metals,
      and the expression levels were dependent on the growth medium and growth phase.
      Expression of cadA2 and czcCBA1 was nonspecific; both genes were induced by
      Zn(2+), Cd(2+), Pb(2+), Ni(2+), Co(2+), and Hg(2+). On the other hand,
      remarkably, expression of cadA1 was induced only by Zn(2+). Possible roles of
      distinct but simultaneously functioning transporters are discussed.

PMID- 18065535
TI  - Mesaconyl-coenzyme A hydratase, a new enzyme of two central carbon metabolic
      pathways in bacteria.
AB  - The coenzyme A (CoA)-activated C5-dicarboxylic acids mesaconyl-CoA and beta
      methylmalyl-CoA play roles in two as yet not completely resolved central carbon
      metabolic pathways in bacteria. First, these compounds are intermediates in the 3
      hydroxypropionate cycle for autotrophic CO2 fixation in Chloroflexus aurantiacus,
      a phototrophic green nonsulfur bacterium. Second, mesaconyl-CoA and beta
      methylmalyl-CoA are intermediates in the ethylmalonyl-CoA pathway for acetate
      assimilation in various bacteria, e.g., in Rhodobacter sphaeroides,
      Methylobacterium extorquens, and Streptomyces species. In both cases, mesaconyl
      CoA hydratase was postulated to catalyze the interconversion of mesaconyl-CoA and
      beta-methylmalyl-CoA. The putative genes coding for this enzyme in C. aurantiacus
      and R. sphaeroides were cloned and heterologously expressed in Escherichia coli,
      and the proteins were purified and studied. The recombinant homodimeric 80-kDa
      proteins catalyzed the reversible dehydration of erythro-beta-methylmalyl-CoA to
      mesaconyl-CoA with rates of 1,300 micromol min(-1) mg protein(-1). Genes coding
      for similar enzymes with two (R)-enoyl-CoA hydratase domains are present in the
      genomes of Roseiflexus, Methylobacterium, Hyphomonas, Rhodospirillum,
      Xanthobacter, Caulobacter, Magnetospirillum, Jannaschia, Sagittula, Parvibaculum,
      Stappia, Oceanicola, Loktanella, Silicibacter, Roseobacter, Roseovarius,
      Dinoroseobacter, Sulfitobacter, Paracoccus, and Ralstonia species. A similar yet
      distinct class of enzymes containing only one hydratase domain was found in
      various other bacteria, such as Streptomyces species. The role of this widely
      distributed new enzyme is discussed.

PMID- 18065536
TI  - Cyclic dimeric GMP signaling and regulation of surface-associated developmental
      programs.

PMID- 18065537
TI  - Ma-LMM01 infecting toxic Microcystis aeruginosa illuminates diverse cyanophage
      genome strategies.
AB  - Cyanobacteria and their phages are significant microbial components of the
      freshwater and marine environments. We identified a lytic phage, Ma-LMM01,
      infecting Microcystis aeruginosa, a cyanobacterium that forms toxic blooms on the
      surfaces of freshwater lakes. Here, we describe the first sequenced freshwater
      cyanomyovirus genome of Ma-LMM01. The linear, circularly permuted, and terminally
      redundant genome has 162,109 bp and contains 184 predicted protein-coding genes
      and two tRNA genes. The genome exhibits no colinearity with previously sequenced
      genomes of cyanomyoviruses or other Myoviridae. The majority of the predicted
      genes have no detectable homologues in the databases. These findings indicate
      that Ma-LMM01 is a member of a new lineage of the Myoviridae family. The genome
      lacks homologues for the photosynthetic genes that are prevalent in marine
      cyanophages. However, it has a homologue of nblA, which is essential for the
      degradation of the major cyanobacteria light-harvesting complex, the
      phycobilisomes. The genome codes for a site-specific recombinase and two prophage
      antirepressors, suggesting that it has the capacity to integrate into the host
      genome. Ma-LMM01 possesses six genes, including three coding for transposases,
      that are highly similar to homologues found in cyanobacteria, suggesting that
      recent gene transfers have occurred between Ma-LMM01 and its host. We propose
      that the Ma-LMM01 NblA homologue possibly reduces the absorption of excess light
      energy and confers benefits to the phage living in surface waters. This phage
      genome study suggests that light is central in the phage-cyanobacterium
      relationships where the viruses use diverse genetic strategies to control their
      host's photosynthesis.

PMID- 18065538
TI  - CotC-CotU heterodimerization during assembly of the Bacillus subtilis spore coat.
AB  - We report evidence that CotC and CotU, two previously identified components of
      the Bacillus subtilis spore coat, are produced concurrently in the mother cell
      chamber of the sporulating cell under the control of sigmaK and GerE and
      immediately assembled around the forming spore. In the coat, the two proteins
      interact to form a coat component of 23 kDa. The CotU-CotC interaction was not
      detected in two heterologous hosts, suggesting that it occurs only in B.
      subtilis. Monomeric forms of both CotU and CotC failed to be assembled at the
      surface of the developing spore and accumulated in the mother cell compartment of
      cells mutant for cotE. In contrast, neither CotU nor CotC accumulated in the
      mother cell compartment of cells mutant for cotH. These results suggest that CotH
      is required to protect both CotU and CotC in the mother cell compartment of the
      sporangium and that CotE is needed to allow their assembly and subsequent
      interaction at the spore surface.

PMID- 18065539
TI  - Diversity, activity, and evolution of CRISPR loci in Streptococcus thermophilus.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) are
      hypervariable loci widely distributed in prokaryotes that provide acquired
      immunity against foreign genetic elements. Here, we characterize a novel
      Streptococcus thermophilus locus, CRISPR3, and experimentally demonstrate its
      ability to integrate novel spacers in response to bacteriophage. Also, we analyze
      CRISPR diversity and activity across three distinct CRISPR loci in several S.
      thermophilus strains. We show that both CRISPR repeats and cas genes are locus
      specific and functionally coupled. A total of 124 strains were studied, and 109
      unique spacer arrangements were observed across the three CRISPR loci. Overall,
      3,626 spacers were analyzed, including 2,829 for CRISPR1 (782 unique), 173 for
      CRISPR2 (16 unique), and 624 for CRISPR3 (154 unique). Sequence analysis of the
      spacers revealed homology and identity to phage sequences (77%), plasmid
      sequences (16%), and S. thermophilus chromosomal sequences (7%). Polymorphisms
      were observed for the CRISPR repeats, CRISPR spacers, cas genes, CRISPR motif,
      locus architecture, and specific sequence content. Interestingly, CRISPR loci
      evolved both via polarized addition of novel spacers after exposure to foreign
      genetic elements and via internal deletion of spacers. We hypothesize that the
      level of diversity is correlated with relative CRISPR activity and propose that
      the activity is highest for CRISPR1, followed by CRISPR3, while CRISPR2 may be
      degenerate. Globally, the dynamic nature of CRISPR loci might prove valuable for
      typing and comparative analyses of strains and microbial populations. Also,
      CRISPRs provide critical insights into the relationships between prokaryotes and
      their environments, notably the coevolution of host and viral genomes.

PMID- 18065540
TI  - Novel class of mutations of pilS mutants, encoding plasmid R64 type IV prepilin:
      interface of PilS-PilV interactions.
AB  - The type IV pili of plasmid R64 belonging to the type IVB group are required only
      for liquid mating. They consist of the major and minor components PilS pilin and
      PilV adhesin, respectively. PilS pilin is first synthesized as a 22-kDa prepilin
      from the pilS gene and is then processed to a 19-kDa mature pilin by PilU
      prepilin peptidase. In a previous genetic analysis, we identified four classes of
      the pilS mutants (T. Horiuchi and T. Komano, J. Bacteriol. 180:4613-4620, 1998).
      The products of the class I pilS mutants were not processed by prepilin
      peptidase; the products of the class II mutants were not secreted; in the class
      III mutants type IV pili with reduced activities in liquid mating were produced;
      and in the class IV mutants type IV pili with normal activities were produced.
      Here, we describe a novel class, class V, of pilS mutants. Mutations in the pilS
      gene at Gly-56 or Tyr-57 produced type IV pili lacking PilV adhesin, which were
      inactive in liquid mating. Residues 56 and 57 of PilS pilin are suggested to
      function as an interface of PilS-PilV interactions.

PMID- 18065541
TI  - Analysis of genetic relatedness of Haemophilus influenzae isolates by multilocus
      sequence typing.
AB  - The gram-negative bacterium Haemophilus influenzae is a human-restricted
      commensal of the nasopharynx that can also be associated with disease. The
      majority of H. influenzae respiratory isolates lack the genes for capsule
      production and are nontypeable (NTHI). Whereas encapsulated strains are known to
      belong to serotype-specific phylogenetic groups, the structure of the NTHI
      population has not been previously described. A total of 656 H. influenzae
      strains, including 322 NTHI strains, have been typed by multilocus sequence
      typing and found to have 359 sequence types (ST). We performed maximum-parsimony
      analysis of the 359 sequences and calculated the majority-rule consensus of 4,545
      resulting equally most parsimonious trees. Eleven clades were identified,
      consisting of six or more ST on a branch that was present in 100% of trees. Two
      additional clades were defined by branches present in 91% and 82% of trees,
      respectively. Of these 13 clades, 8 consisted predominantly of NTHI strains,
      three were serotype specific, and 2 contained distinct NTHI-specific and serotype
      specific clusters of strains. Sixty percent of NTHI strains have ST within one of
      the 13 clades, and eBURST analysis identified an additional phylogenetic group
      that contained 20% of NTHI strains. There was concordant clustering of certain
      metabolic reactions and putative virulence loci but not of disease source or
      geographic origin. We conclude that well-defined phylogenetic groups of NTHI
      strains exist and that these groups differ in genetic content. These observations
      will provide a framework for further study of the effect of genetic diversity on
      the interaction of NTHI with the host.

PMID- 18065542
TI  - A point mutation in the two-component regulator PhoP-PhoR accounts for the
      absence of polyketide-derived acyltrehaloses but not that of phthiocerol
      dimycocerosates in Mycobacterium tuberculosis H37Ra.
AB  - Similarities between Mycobacterium tuberculosis phoP-phoR mutants and the
      attenuated laboratory strain M. tuberculosis H37Ra in terms of morphological and
      cytochemical properties, lipid content, gene expression and virulence attenuation
      prompted us to analyze the functionality of this two-component regulator in the
      latter strain. Sequence analysis revealed a base substitution resulting in a one
      amino-acid change in the likely DNA-binding region of PhoP in H37Ra relative to
      H37Rv. Using gel-shift assays, we show that this mutation abrogates the ability
      of the H37Ra PhoP protein to bind to a 40-bp segment of its own promoter.
      Consistent with this result, the phoP gene from H37Rv but not that from H37Ra was
      able to restore the synthesis of sulfolipids, diacyltrehaloses and
      polyacyltrehaloses in an isogenic phoP-phoR knock-out mutant of M. tuberculosis
      Moreover, complementation of H37Ra with phoP from H37Rv fully restored
      sulfolipid, diacyltrehalose and polyacyltrehalose synthesis, clearly indicating
      that the lack of production of these lipids in H37Ra is solely due to the point
      mutation in phoP. Using a pks2-3/4 knock-out mutant of M. tuberculosis H37Rv,
      evidence is further provided that the above-mentioned polyketide-derived
      acyltrehaloses do not significantly contribute to the virulence of the tubercle
      bacillus in a mouse model of infection. Reasons for the attenuation of H37Ra thus
      most likely stand in other virulence factors, many of which are expected to
      belong to the PhoP regulon and another of which, unrelated to PhoP, appears to be
      the lack of production of phthiocerol dimycocerosates in this strain.

PMID- 18065543
TI  - Influence of the spxB gene on competence in Streptococcus pneumoniae.
AB  - In Streptococcus pneumoniae expression of pyruvate oxidase (SpxB) peaks during
      the early growth phase, coincident with the time of natural competence. This
      study investigated whether SpxB influences parameters of competence, such as
      spontaneous transformation frequency, expression of competence genes, and DNA
      release. Knockout of the spxB gene in strain D39 abolished spontaneous
      transformation (compared to a frequency of 6.3 x 10(-6) in the parent strain [P <
      0.01]). It also reduced expression levels of comC and recA as well as DNA release
      from bacterial cells significantly during the early growth phase, coincident with
      the time of spontaneous competence in the parent strain. In the spxB mutant,
      supplementation with competence-stimulating peptide 1 (CSP-1) restored
      transformation (rate, 1.8 x 10(-2)). This speaks against the role of SpxB as a
      necessary source of energy for competence. Neither supplementation with CSP-1 nor
      supplementation with the SpxB products H2O2 and acetate altered DNA release.
      Supplementation of the parent strain with catalase did not reduce DNA release
      significantly. In conclusion, the pneumococcal spxB gene influences competence;
      however, the mechanism remains elusive.

PMID- 18065544
TI  - PhoP-PhoP interaction at adjacent PhoP binding sites is influenced by protein
      phosphorylation.
AB  - Mycobacterium tuberculosis PhoP regulates the expression of unknown virulence
      determinants and the biosynthesis of complex lipids. PhoP, like other members of
      the OmpR family, comprises a phosphorylation domain at the amino-terminal half
      and a DNA-binding domain at the carboxy-terminal half of the protein. To explore
      structural effect of protein phosphorylation and to examine effect of
      phosphorylation on DNA binding, purified PhoP was phosphorylated by acetyl
      phosphate in a reaction that was dependent on Mg2+ and Asp-71. Protein
      phosphorylation was not required for DNA binding; however, phosphorylation
      enhanced in vitro DNA binding through protein-protein interaction(s). Evidence is
      presented here that the protein-protein interface is different in the
      unphosphorylated and phosphorylated forms of PhoP and that specific DNA binding
      plays a critical role in changing the nature of the protein-protein interface. We
      show that phosphorylation switches the transactivation domain to a different
      conformation, which specifies additional protein-protein contacts between PhoP
      protomers bound to adjacent cognate sites. Together, our observations raise the
      possibility that PhoP, in the unphosphorylated and phosphorylated forms, may be
      capable of adopting different orientations as it binds to a vast array of genes
      to activate or repress transcription.

PMID- 18065545
TI  - Phage response to CRISPR-encoded resistance in Streptococcus thermophilus.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) and their
      associated genes are linked to a mechanism of acquired resistance against
      bacteriophages. Bacteria can integrate short stretches of phage-derived sequences
      (spacers) within CRISPR loci to become phage resistant. In this study, we further
      characterized the efficiency of CRISPR1 as a phage resistance mechanism in
      Streptococcus thermophilus. First, we show that CRISPR1 is distinct from
      previously known phage defense systems and is effective against the two main
      groups of S. thermophilus phages. Analyses of 30 bacteriophage-insensitive
      mutants of S. thermophilus indicate that the addition of one new spacer in
      CRISPR1 is the most frequent outcome of a phage challenge and that the iterative
      addition of spacers increases the overall phage resistance of the host. The added
      new spacers have a size of between 29 to 31 nucleotides, with 30 being by far the
      most frequent. Comparative analysis of 39 newly acquired spacers with the
      complete genomic sequences of the wild-type phages 2972, 858, and DT1
      demonstrated that the newly added spacer must be identical to a region (named
      proto-spacer) in the phage genome to confer a phage resistance phenotype.
      Moreover, we found a CRISPR1-specific sequence (NNAGAAW) located downstream of
      the proto-spacer region that is important for the phage resistance phenotype.
      Finally, we show through the analyses of 20 mutant phages that virulent phages
      are rapidly evolving through single nucleotide mutations as well as deletions, in
      response to CRISPR1.

PMID- 18065546
TI  - Role of the Clp system in stress tolerance, biofilm formation, and intracellular
      invasion in Porphyromonas gingivalis.
AB  - Clp proteases and chaperones are ubiquitous among prokaryotes and eukaryotes, and
      in many pathogenic bacteria the Clp stress response system is also involved in
      regulation of virulence properties. In this study, the roles of ClpB, ClpC, and
      ClpXP in stress resistance, homotypic and heterotypic biofilm formation, and
      intracellular invasion in the oral opportunistic pathogen Porphyromonas
      gingivalis were investigated. Absence of ClpC and ClpXP, but not ClpB, resulted
      in diminished tolerance to high temperatures. Response to oxidative stress was
      not affected by the loss of any of the Clp proteins. The clpC and clpXP mutants
      demonstrated elevated monospecies biofilm formation, and the absence of ClpXP
      also enhanced heterotypic P. gingivalis-Streptococcus gordonii biofilm formation.
      All clp mutants adhered to gingival epithelial cells to the same level as the
      wild type; however, ClpC and ClpXP were found to be necessary for entry into host
      epithelial cells. ClpB did not play a role in entry but was required for
      intracellular replication and survival. ClpXP negatively regulated the surface
      exposure of the minor fimbrial (Mfa) protein subunit of P. gingivalis, which
      stimulates biofilm formation but interferes with epithelial cell entry.
      Collectively, these results show that the Clp protease complex and chaperones
      control several processes that are important for the colonization and survival of
      P. gingivalis in the oral cavity.

PMID- 18065548
TI  - Lipopolysaccharide O-antigen chain length regulation in Pseudomonas aeruginosa
      serogroup O11 strain PA103.
AB  - The Wzz proteins are important for determining the length of the O-antigen side
      chain attached to lipopolysaccharide (LPS). Several bacteria, including
      Pseudomonas aeruginosa strain PAO1 (serogroup O5), produce two such proteins
      responsible for the preference of two different chain lengths on the surface. Our
      group has previously identified one wzz gene (wzz1) within the O-antigen locus of
      P. aeruginosa strain PA103 (serogroup O11). In this study we have identified the
      second wzz gene (wzz2), located in the same region of the genome and with 92%
      similarity to PAO1's wzz2 gene. Mutations were generated in both wzz genes by
      interruption with antibiotic resistance cassettes, and the effects of these
      mutations were characterized. Wild-type PA103 prefers two O-antigen chain
      lengths, referred to as long and very long. The expression of the long O-antigen
      chain length was reduced in the wzz1 mutant, indicating the Wzz1 protein is
      important for this chain length preference. The wzz2 mutant, on the other hand,
      was missing O-antigens of the very long chain length, indicating the Wzz2 protein
      is responsible for the production of very long O-antigen. The effects of the wzz
      mutations on virulence were also investigated. In both serum sensitivity assays
      and a mouse pneumonia model of infection, the wzz1 mutants exhibited greater
      defects in virulence compared to either wild-type PA103 or the wzz2 mutant,
      indicating the long chain length plays a greater role during these infectious
      processes.

PMID- 18065547
TI  - Moraxella catarrhalis synthesizes an autotransporter that is an acid phosphatase.
AB  - Moraxella catarrhalis O35E was shown to synthesize a 105-kDa protein that has
      similarity to both acid phosphatases and autotransporters. The N-terminal portion
      of the M. catarrhalis acid phosphatase A (MapA) was most similar (the BLAST
      probability score was 10(-10)) to bacterial class A nonspecific acid
      phosphatases. The central region of the MapA protein had similarity to passenger
      domains of other autotransporter proteins, whereas the C-terminal portion of MapA
      resembled the translocation domain of conventional autotransporters. Cloning and
      expression of the M. catarrhalis mapA gene in Escherichia coli confirmed the
      presence of acid phosphatase activity in the MapA protein. The MapA protein was
      shown to be localized to the outer membrane of M. catarrhalis and was not
      detected either in the soluble cytoplasmic fraction from disrupted M. catarrhalis
      cells or in the spent culture supernatant fluid from M. catarrhalis. Use of the
      predicted MapA translocation domain in a fusion construct with the passenger
      domain from another predicted M. catarrhalis autotransporter confirmed the
      translocation ability of this MapA domain. Inactivation of the mapA gene in M.
      catarrhalis strain O35E reduced the acid phosphatase activity expressed by this
      organism, and this mutation could be complemented in trans with the wild-type
      mapA gene. Nucleotide sequence analysis of the mapA gene from six M. catarrhalis
      strains showed that this protein was highly conserved among strains of this
      pathogen. Site-directed mutagenesis of a critical histidine residue (H233A) in
      the predicted active site of the acid phosphatase domain in MapA eliminated acid
      phosphatase activity in the recombinant MapA protein. This is the first
      description of an autotransporter protein that expresses acid phosphatase
      activity.

PMID- 18065549
TI  - Pseudomonas aeruginosa exhibits sliding motility in the absence of type IV pili
      and flagella.
AB  - Pseudomonas aeruginosa exhibits swarming motility on 0.5 to 1% agar plates in the
      presence of specific carbon and nitrogen sources. We have found that PAO1 double
      mutants expressing neither flagella nor type IV pili (fliC pilA) display sliding
      motility under the same conditions. Sliding motility was inhibited when type IV
      pilus expression was restored; like swarming motility, it also decreased in the
      absence of rhamnolipid surfactant production. Transposon insertions in gacA and
      gacS increased sliding motility and restored tendril formation to spreading
      colonies, while transposon insertions in retS abolished motility. These changes
      in motility were not accompanied by detectable changes in rhamnolipid surfactant
      production or by the appearance of bacterial surface structures that might power
      sliding motility. We propose that P. aeruginosa requires flagella during swarming
      to overcome adhesive interactions mediated by type IV pili. The apparent
      dependence of sliding motility on environmental cues and regulatory pathways that
      also affect swarming motility suggests that both forms of motility are influenced
      by similar cohesive factors that restrict translocation, as well as by dispersive
      factors that facilitate spreading. Studies of sliding motility may be
      particularly well-suited for identifying factors other than pili and flagella
      that affect community behaviors of P. aeruginosa.

PMID- 18065551
TI  - Chemotaxis of Escherichia coli to pyrimidines: a new role for the signal
      transducer tap.
AB  - Escherichia coli exhibits chemotactic responses to sugars, amino acids, and
      dipeptides, and the responses are mediated by methyl-accepting chemotaxis
      proteins (MCPs). Using capillary assays, we demonstrated that Escherichia coli
      RP437 is attracted to the pyrimidines thymine and uracil and the response was
      constitutively expressed under all tested growth conditions. All MCP mutants
      lacking the MCP Tap protein showed no response to pyrimidines, suggesting that
      Tap, which is known to mediate dipeptide chemotaxis, is required for pyrimidine
      chemotaxis. In order to confirm the role of Tap in pyrimidine chemotaxis, we
      constructed chimeric chemoreceptors (Tapsr and Tsrap), in which the periplasmic
      and cytoplasmic domains of Tap and Tsr were switched. When Tapsr and Tsrap were
      individually expressed in an E. coli strain lacking all four native MCPs, Tapsr
      mediated chemotaxis toward pyrimidines and dipeptides, but Tsrap did not
      complement the chemotaxis defect. The addition of the C-terminal 19 amino acids
      from Tsr to the C terminus of Tsrap resulted in a functional chemoreceptor that
      mediated chemotaxis to serine but not pyrimidines or dipeptides. These results
      indicate that the periplasmic domain of Tap is responsible for detecting
      pyrimidines and the Tsr signaling domain confers on Tapsr the ability to mediate
      efficient chemotaxis. A mutant lacking dipeptide binding protein (DBP) was wild
      type for pyrimidine taxis, indicating that DBP, which is the primary
      chemoreceptor for dipeptides, is not responsible for detecting pyrimidines. It is
      not yet known whether Tap detects pyrimidines directly or via an additional
      chemoreceptor protein.

PMID- 18065550
TI  - Secreted-protein response to sigmaU activity in Streptomyces coelicolor.
AB  - The filamentous bacterium Streptomyces coelicolor forms an aerial mycelium as a
      prerequisite to sporulation, which occurs in the aerial hyphae. Uncontrolled
      activity of the extracytoplasmic function sigma factor sigmaU blocks the process
      of aerial mycelium formation in this organism. Using a green fluorescent protein
      transcriptional reporter, we have demonstrated that sigU transcription is
      autoregulated. We have defined a sigmaU-dependent promoter sequence and used this
      to identify 22 likely sigmaU regulon members in the S. coelicolor genome. Since
      many of these genes encode probable secreted proteins, we characterized the
      extracellular proteome of a mutant with high sigmaU activity caused by disruption
      of rsuA, the presumed cognate anti-sigma factor of sigmaU. This mutant secreted a
      much greater quantity and diversity of proteins than the wild-type strain.
      Peptide mass fingerprinting was used to identify 79 proteins from the rsuA mutant
      culture supernatant. The most abundant species, SCO2217, SCO0930, and SCO2207,
      corresponded to secreted proteins or lipoproteins of unknown functions whose
      genes are in the proposed sigmaU regulon. Several unique proteases were also
      detected in the extracellular proteome of the mutant, and the levels of the
      protease inhibitor SCO0762 were much reduced compared to those of the wild type.
      Consequently, extracellular protease activity was elevated about fourfold in the
      rsuA mutant. The functions of the proteins secreted as a result of sigmaU
      activity may be important for combating cell envelope stress and modulating
      morphological differentiation in S. coelicolor.

PMID- 18065552
TI  - Genomic survey and gene expression analysis of the basic leucine zipper
      transcription factor family in rice.
AB  - The basic leucine (Leu) zipper (bZIP) proteins compose a family of
      transcriptional regulators present exclusively in eukaryotes. The bZIP proteins
      characteristically harbor a bZIP domain composed of two structural features: a
      DNA-binding basic region and the Leu zipper dimerization region. They have been
      shown to regulate diverse plant-specific phenomena, including seed maturation and
      germination, floral induction and development, and photomorphogenesis, and are
      also involved in stress and hormone signaling. We have identified 89 bZIP
      transcription factor-encoding genes in the rice (Oryza sativa) genome. Their
      chromosomal distribution and sequence analyses suggest that the bZIP
      transcription factor family has evolved via gene duplication. The phylogenetic
      relationship among rice bZIP domains as well as with bZIP domains from other
      plant bZIP factors suggests that homologous bZIP domains exist in plants. Similar
      intron/exon structural patterns were observed in the basic and hinge regions of
      their bZIP domains. Detailed sequence analysis has been done to identify
      additional conserved motifs outside the bZIP domain and to predict their DNA
      binding site specificity as well as dimerization properties, which has helped
      classify them into different groups and subfamilies, respectively. Expression of
      bZIP transcription factor-encoding genes has been analyzed by full-length cDNA
      and expressed sequence tag-based expression profiling. This expression profiling
      was complemented by microarray analysis. The results indicate specific or
      coexpression patterns of rice bZIP transcription factors starting from floral
      transition to various stages of panicle and seed development. bZIP transcription
      factor-encoding genes in rice also displayed differential expression patterns in
      rice seedlings in response to abiotic stress and light irradiation. An effort has
      been made to link the structure and expression pattern of bZIP transcription
      factor-encoding genes in rice to their function, based on the information
      obtained from our analyses and earlier known results. This information will be
      important for functional characterization of bZIP transcription factors in rice.

PMID- 18065553
TI  - Pectin methyl esterase inhibits intrusive and symplastic cell growth in
      developing wood cells of Populus.
AB  - Wood cells, unlike most other cells in plants, grow by a unique combination of
      intrusive and symplastic growth. Fibers grow in diameter by diffuse symplastic
      growth, but they elongate solely by intrusive apical growth penetrating the
      pectin-rich middle lamella that cements neighboring cells together. In contrast,
      vessel elements grow in diameter by a combination of intrusive and symplastic
      growth. We demonstrate that an abundant pectin methyl esterase (PME; EC 3.1.1.11)
      from wood-forming tissues of hybrid aspen (Populus tremula x tremuloides) acts as
      a negative regulator of both symplastic and intrusive growth of developing wood
      cells. When PttPME1 expression was up- and down-regulated in transgenic aspen
      trees, the PME activity in wood-forming tissues was correspondingly altered. PME
      removes methyl ester groups from homogalacturonan (HG) and transgenic trees had
      modified HG methylesterification patterns, as demonstrated by two-dimensional
      nuclear magnetic resonance and immunostaining using PAM1 and LM7 antibodies. In
      situ distributions of PAM1 and LM7 epitopes revealed changes in pectin
      methylesterification in transgenic trees that were specifically localized in
      expanding wood cells. The results show that en block deesterification of HG by
      PttPME1 inhibits both symplastic growth and intrusive growth. PttPME1 is
      therefore involved in mechanisms determining fiber width and length in the wood
      of aspen trees.

PMID- 18065554
TI  - Firefly luciferase complementation imaging assay for protein-protein interactions
      in plants.
AB  - The development of sensitive and versatile techniques to detect protein-protein
      interactions in vivo is important for understanding protein functions. The
      previously described techniques, fluorescence resonance energy transfer and
      bimolecular fluorescence complementation, which are used widely for protein
      protein interaction studies in plants, require extensive instrumentation. To
      facilitate protein-protein interaction studies in plants, we adopted the
      luciferase complementation imaging assay. The amino-terminal and carboxyl
      terminal halves of the firefly luciferase reconstitute active luciferase enzyme
      only when fused to two interacting proteins, and that can be visualized with a
      low-light imaging system. A series of plasmid constructs were made to enable the
      transient expression of fusion proteins or generation of stable transgenic
      plants. We tested nine pairs of proteins known to interact in plants, including
      Pseudomonas syringae bacterial effector proteins and their protein targets in the
      plant, proteins of the SKP1-Cullin-F-box protein E3 ligase complex, the HSP90
      chaperone complex, components of disease resistance protein complex, and
      transcription factors. In each case, strong luciferase complementation was
      observed for positive interactions. Mutants that are known to compromise protein
      protein interactions showed little or much reduced luciferase activity. Thus, the
      assay is simple, reliable, and quantitative in detection of protein-protein
      interactions in plants.

PMID- 18065555
TI  - The contribution of photosynthesis to the red light response of stomatal
      conductance.
AB  - To determine the contribution of photosynthesis on stomatal conductance, we
      contrasted the stomatal red light response of wild-type tobacco (Nicotiana
      tabacum 'W38') with that of plants impaired in photosynthesis by antisense
      reductions in the content of either cytochrome b(6)f complex (anti-b/f plants) or
      Rubisco (anti-SSU plants). Both transgenic genotypes showed a lowered content of
      the antisense target proteins in guard cells as well as in the mesophyll. In the
      anti-b/f plants, CO(2) assimilation rates were proportional to leaf cytochrome
      b(6)f content, but there was little effect on stomatal conductance and the rate
      of stomatal opening. To compare the relationship between photosynthesis and
      stomatal conductance, wild-type plants and anti-SSU plants were grown at 30 and
      300 micromol photon m(-2) s(-1) irradiance (low light and medium light [ML],
      respectively). Growth in ML increased CO(2) assimilation rates and stomatal
      conductance in both genotypes. Despite the significantly lower CO(2) assimilation
      rate in the anti-SSU plants, the differences in stomatal conductance between the
      genotypes were nonsignificant at either growth irradiance. Irrespective of plant
      genotype, stomatal density in the two leaf surfaces was 2-fold higher in ML-grown
      plants than in low-light-grown plants and conductance normalized to stomatal
      density was unaffected by growth irradiance. We conclude that the red light
      response of stomatal conductance is independent of the concurrent photosynthetic
      rate of the guard cells or of that of the underlying mesophyll. Furthermore, we
      suggest that the correlation of photosynthetic capacity and stomatal conductance
      observed under different light environments is caused by signals largely
      independent of photosynthesis.

PMID- 18065556
TI  - Identification, biochemical characterization, and subcellular localization of
      allantoate amidohydrolases from Arabidopsis and soybean.
AB  - Allantoate amidohydrolases (AAHs) hydrolize the ureide allantoate to
      ureidoglycolate, CO(2), and two molecules of ammonium. Allantoate degradation is
      required to recycle purine-ring nitrogen in all plants. Tropical legumes
      additionally transport fixed nitrogen via allantoin and allantoate into the
      shoot, where it serves as a general nitrogen source. AAHs from Arabidopsis
      (Arabidopsis thaliana; AtAAH) and from soybean (Glycine max; GmAAH) were cloned,
      expressed in planta as StrepII-tagged variants, and highly purified from leaf
      extracts. Both proteins form homodimers and release 2 mol ammonium/mol
      allantoate. Therefore, they can truly be classified as AAHs. The kinetic
      constants determined and the half-maximal activation by 2 to 3 microm manganese
      are consistent with allantoate being the in vivo substrate of manganese-loaded
      AAHs. The enzymes were strongly inhibited by micromolar concentrations of
      fluoride as well as by borate, and by millimolar concentrations of L-asparagine
      and L-aspartate but not D-asparagine. L-Asparagine likely functions as
      competitive inhibitor. An Ataah T-DNA mutant, unable to grow on allantoin as sole
      nitrogen source, is rescued by the expression of StrepII-tagged variants of AtAAH
      and GmAAH, demonstrating that both proteins are functional in vivo. Similarly, an
      allantoinase (aln) mutant is rescued by a tagged AtAln variant. Fluorescent
      fusion proteins of allantoinase and both AAHs localize to the endoplasmic
      reticulum after transient expression and in transgenic plants. These findings
      demonstrate that after the generation of allantoin in the peroxisome, plant
      purine degradation continues in the endoplasmic reticulum.

PMID- 18065557
TI  - An Arabidopsis purple acid phosphatase with phytase activity increases foliar
      ascorbate.
AB  - Ascorbate (AsA) is the most abundant antioxidant in plant cells and a cofactor
      for a large number of key enzymes. However, the mechanism of how AsA levels are
      regulated in plant cells remains unknown. The Arabidopsis (Arabidopsis thaliana)
      activation-tagged mutant AT23040 showed a pleiotropic phenotype, including ozone
      resistance, rapid growth, and leaves containing higher AsA than wild-type plants.
      The phenotype was caused by activation of a purple acid phosphatase (PAP) gene,
      AtPAP15, which contains a dinuclear metal center in the active site. AtPAP15 was
      universally expressed in all tested organs in wild-type plants. Overexpression of
      AtPAP15 with the 35S cauliflower mosaic virus promoter produced mutants with up
      to 2-fold increased foliar AsA, 20% to 30% decrease in foliar phytate, enhanced
      salt tolerance, and decreased abscisic acid sensitivity. Two independent SALK T
      DNA insertion mutants in AtPAP15 had 30% less foliar AsA and 15% to 20% more
      phytate than wild-type plants and decreased tolerance to abiotic stresses. Enzyme
      activity of partially purified AtPAP15 from plant crude extract and recombinant
      AtPAP15 expressed in bacteria and yeast was highest when phytate was used as
      substrate, indicating that AtPAP15 is a phytase. Recombinant AtPAP15 also showed
      enzyme activity on the substrate myoinositol-1-phosphate, indicating that the
      AtPAP15 is a phytase that hydrolyzes myoinositol hexakisphosphate to yield
      myoinositol and free phosphate. Myoinositol is a known precursor for AsA
      biosynthesis in plants. Thus, AtPAP15 may modulate AsA levels by controlling the
      input of myoinositol into this branch of AsA biosynthesis in Arabidopsis.

PMID- 18065558
TI  - Transgenic expression of a fungal endo-polygalacturonase increases plant
      resistance to pathogens and reduces auxin sensitivity.
AB  - Polygalacturonases (PGs), enzymes that hydrolyze the homogalacturonan of the
      plant cell wall, are virulence factors of several phytopathogenic fungi and
      bacteria. On the other hand, PGs may activate defense responses by releasing
      oligogalacturonides (OGs) perceived by the plant cell as host-associated
      molecular patterns. Tobacco (Nicotiana tabacum) and Arabidopsis (Arabidopsis
      thaliana) plants expressing a fungal PG (PG plants) have a reduced content of
      homogalacturonan. Here, we show that PG plants are more resistant to microbial
      pathogens and have constitutively activated defense responses. Interestingly,
      either in tobacco PG or wild-type plants treated with OGs, resistance to fungal
      infection is suppressed by exogenous auxin, whereas sensitivity to auxin of PG
      plants is reduced in different bioassays. The altered plant defense responses and
      auxin sensitivity in PG plants may reflect an increased accumulation of OGs and
      subsequent antagonism of auxin action. Alternatively, it may be a consequence of
      perturbations of cellular physiology and elevated defense status as a result of
      altered cell wall architecture.

PMID- 18065559
TI  - The phosphoproteome of a Chlamydomonas reinhardtii eyespot fraction includes key
      proteins of the light signaling pathway.
AB  - Flagellate green algae have developed a visual system, the eyespot apparatus,
      which allows the cell to phototax. In a recent proteomic approach, we identified
      202 proteins from a fraction enriched in eyespot apparatuses of Chlamydomonas
      reinhardtii. Among these proteins, five protein kinases and two protein
      phosphatases were present, indicating that reversible protein phosphorylation
      occurs in the eyespot. About 20 major phosphoprotein bands were detected in
      immunoblots of eyespot proteins with an anti-phosphothreonine antibody. Toward
      the profiling of the targets of protein kinases in the eyespot fraction, we
      analyzed its phosphoproteome. The solubilized proteins of the eyespot fraction
      were treated with the endopeptidases LysC and trypsin prior to enrichment of
      phosphopeptides with immobilized metal-ion affinity chromatography.
      Phosphopeptides were analyzed by nano-liquid chromatography-electrospray
      ionization-mass spectrometry (MS) with MS/MS as well as neutral-loss-triggered
      MS/MS/MS spectra. We were able to identify 68 different phosphopeptides along
      with 52 precise in vivo phosphorylation sites corresponding to 32 known proteins
      of the eyespot fraction. Among the identified phosphoproteins are enzymes of
      carotenoid and fatty acid metabolism, putative signaling components, such as a
      SOUL heme-binding protein, a Ca(2+)-binding protein, and an unusual protein
      kinase, but also several proteins with unknown function. Notably, two unique
      photoreceptors, channelrhodopsin-1 and channelrhodopsin-2, contain three and one
      phosphorylation sites, respectively. Phosphorylation of both photoreceptors
      occurs in the cytoplasmatic loop next to their seven transmembrane regions in a
      similar distance to that observed in vertebrate rhodopsins, implying functional
      importance for regulation of these directly light-gated ion channels relevant for
      the photoresponses of C. reinhardtii.

PMID- 18065560
TI  - AffyTrees: facilitating comparative analysis of Affymetrix plant microarray
      chips.
AB  - Microarrays measure the expression of large numbers of genes simultaneously and
      can be used to delve into interaction networks involving many genes at a time.
      However, it is often difficult to decide to what extent knowledge about the
      expression of genes gleaned in one model organism can be transferred to other
      species. This can be examined either by measuring the expression of genes of
      interest under comparable experimental conditions in other species, or by
      gathering the necessary data from comparable microarray experiments. However, it
      is essential to know which genes to compare between the organisms. To facilitate
      comparison of expression data across different species, we have implemented a Web
      based software tool that provides information about sequence orthologs across a
      range of Affymetrix microarray chips. AffyTrees provides a quick and easy way of
      assigning which probe sets on different Affymetrix chips measure the expression
      of orthologous genes. Even in cases where gene or genome duplications have
      complicated the assignment, groups of comparable probe sets can be identified.
      The phylogenetic trees provide a resource that can be used to improve sequence
      annotation and detect biases in the sequence complement of Affymetrix chips.
      Being able to identify sequence orthologs and recognize biases in the sequence
      complement of chips is necessary for reliable cross-species microarray
      comparison. As the amount of work required to generate a single phylogeny in a
      nonautomated manner is considerable, AffyTrees can greatly reduce the workload
      for scientists interested in large-scale cross-species comparisons.

PMID- 18065561
TI  - Altered profile of secondary metabolites in the root exudates of Arabidopsis ATP
      binding cassette transporter mutants.
AB  - Following recent indirect evidence suggesting a role for ATP-binding cassette
      (ABC) transporters in root exudation of phytochemicals, we identified 25 ABC
      transporter genes highly expressed in the root cells most likely to be involved
      in secretion processes. Of these 25 genes, we also selected six full-length ABC
      transporters and a half-size transporter for in-depth molecular and biochemical
      analyses. We compared the exuded root phytochemical profiles of these seven ABC
      transporter mutants to those of the wild type. There were three nonpolar
      phytochemicals missing in various ABC transporter mutants compared to the wild
      type when the samples were analyzed by high-performance liquid chromatography
      mass spectrometry. These data suggest that more than one ABC transporter can be
      involved in the secretion of a given phytochemical and that a transporter can be
      involved in the secretion of more than one secondary metabolite. The primary and
      secondary metabolites present in the root exudates of the mutants were also
      analyzed by gas chromatography-mass spectrometry, which allowed for the
      identification of groups of compounds differentially found in some of the mutants
      compared to the wild type. For instance, the mutant Atpdr6 secreted a lower level
      of organic acids and Atmrp2 secreted a higher level of amino acids as compared to
      the wild type. We conclude that the release of phytochemicals by roots is
      partially controlled by ABC transporters.

PMID- 18065563
TI  - Characterization of the interaction of a novel Stagonospora nodorum host
      selective toxin with a wheat susceptibility gene.
AB  - Recent work suggests that the Stagonospora nodorum-wheat pathosystem is
      controlled by host-selective toxins (HSTs; SnToxA, SnTox1, and SnTox2) that
      interact directly or indirectly with dominant host genes (Tsn1, Snn1, and Snn2)
      to induce disease. Here we describe and characterize a novel HST designated
      SnTox3, and the corresponding wheat sensitivity/susceptibility gene identified on
      chromosome arm 5BS, which we designated as Snn3. SnTox3 is a proteinaceous
      necrosis-inducing toxin between 10 and 30 kD in size. The S. nodorum isolates
      Sn1501 (SnToxA-, SnTox2+, and SnTox3+), SN15 (SnToxA+, SnTox2+, and SnTox3+), and
      SN15KO18, a strain of SN15 with a disrupted form of SnToxA, were evaluated on a
      population of wheat recombinant inbred lines. A compatible Snn3-SnTox3
      interaction played a significant role in the development of disease caused by
      isolates Sn1501 and SN15KO18, with Snn2 being epistatic to Snn3. Snn3 was not
      significantly associated with disease caused by SN15 presumably due to the major
      effects observed for Snn2 and Tsn1, which were largely additive. This work
      introduces a fourth HST produced by S. nodorum and builds on the notion that the
      S. nodorum-wheat pathosystem is largely based on multiple host-toxin interactions
      that follow an inverse gene-for-gene scenario.

PMID- 18065562
TI  - Comparisons of LIPOXYGENASE3- and JASMONATE-RESISTANT4/6-silenced plants reveal
      that jasmonic acid and jasmonic acid-amino acid conjugates play different roles
      in herbivore resistance of Nicotiana attenuata.
AB  - Whereas jasmonic acid (JA) and its amino acid conjugates, particularly JA
      isoleucine (Ile), are known to play important roles in plant-herbivore
      interactions, whether other compounds also function as signals independently of
      JA-Ile and whether conjugates elicit systemic responses are unknown. To answer
      these questions, we simultaneously silenced JASMONATE-RESISTANT4 (JAR4) and JAR6,
      two functionally redundant enzymes in Nicotiana attenuata that conjugate JA to
      amino acids to produce plants (irjar4/6) with low levels of JA-Ile, JA-leucine
      (Leu), and JA-valine (Val; <16% of wild type). As expected, irjar4/6 plants are
      more vulnerable to herbivore attack, but only JA-Ile -- not JA-Leu or JA-Val --
      applications restored the resistance of irjar4/6 plants, suggesting that JA-Leu
      and JA-Val do not mediate herbivore defense responses. Interestingly, the direct
      defense traits of irjar4/6 plants are significantly higher than those in
      LIPOXYGENASE3 (LOX3)-silenced (aslox3) plants, which are impaired in JA
      biosynthesis, and JA-Ile treatment could not fully restore the resistance of
      aslox3 plants. We thus conclude that JA, its precursors, or other metabolites
      complement the function of JA-Ile by eliciting a panoply of induced defenses.
      Similarly, transcriptional profiling of wild-type, irjar4/6, and aslox3 plants
      with microarrays demonstrated that JA-Ile and JA play overlapping yet distinct
      roles in herbivore defense. Analysis of transcripts in distal tissues
      demonstrated that JAR activity is essential in eliciting systemic responses.
      However, attempts to recover JA-(13)C(6)-Ile in systemic leaves and roots after
      feeding wounded leaves with (13)C(6)-Ile were unsuccessful, suggesting that JA
      Ile is not a long-distance signal, but is rather synthesized after the arrival of
      an unknown mobile signal to systemic tissues.

PMID- 18065564
TI  - Kinetics and mechanism of Dionaea muscipula trap closing.
AB  - The Venus flytrap (Dionaea muscipula) possesses an active trapping mechanism to
      capture insects with one of the most rapid movements in the plant kingdom, as
      described by Darwin. This article presents a detailed experimental investigation
      of trap closure by mechanical and electrical stimuli and the mechanism of this
      process. Trap closure consists of three distinctive phases: a silent phase with
      no observable movement; an accelerated movement of the lobes; and the relaxation
      of the lobes in their closed state, resulting in a new equilibrium. Uncouplers
      and blockers of membrane channels were used to investigate the mechanisms of
      different phases of closing. Uncouplers increased trap closure delay and
      significantly decreased the speed of trap closure. Ion channel blockers and
      aquaporin inhibitors increased time of closing. Transmission of a single
      electrical charge between a lobe and the midrib causes closure of the trap and
      induces an electrical signal propagating between both lobes and midrib. The Venus
      flytrap can accumulate small subthreshold charges, and when the threshold value
      is reached, the trap closes. Repeated application of smaller charges demonstrates
      the summation of stimuli. The cumulative character of electrical stimuli points
      to the existence of electrical memory in the Venus flytrap. The observed fast
      movement can be explained by the hydroelastic curvature model without invoking
      buckling instability. The new hydroelastic curvature mechanism provides an
      accurate description of the authors' experimental data.

PMID- 18065565
TI  - The ACA10 Ca2+-ATPase regulates adult vegetative development and inflorescence
      architecture in Arabidopsis.
AB  - The Arabidopsis (Arabidopsis thaliana) compact inflorescence (cif) genotype
      causes altered adult vegetative development and a reduction in elongation of
      inflorescence internodes resulting in formation of floral clusters. The cif trait
      requires both a recessive mutation, cif1, and the activity of a naturally
      occurring dominant allele of an unlinked gene, CIF2(D). We show here that the
      pseudoverticillata mutation is allelic with cif1 and that the product of the CIF1
      gene is ACA10, a member of the large family of P-type Ca(2+)-ATPases found in
      higher plants. T-DNA insertion mutations in ACA10, but not in the two other
      Arabidopsis plasma membrane Ca(2+)-ATPase-encoding genes, ACA8 and ACA9, cause a
      cif phenotype when combined with the dominant CIF2(D) modifier allele. Therefore,
      ACA10 has a unique function in regulating adult phase growth and inflorescence
      development. The wild-type ACA8 and ACA10 mRNAs are present at similar levels,
      and the two promoter-beta-glucuronidase fusion transgenes show very similar
      expression patterns. Moreover, transformation of the cif mutant with an extra
      copy of the ACA8 gene, which causes overexpression of the ACA8 transcript, can
      complement the cif phenotype. This suggests that these two Ca(2+) pump genes have
      distinct but related activities and that their differential functions can be
      altered by relatively small changes in their patterns or levels of expression.
      The correspondence between cif1 and mutations in ACA10 establishes a genetic link
      between calcium transport, vegetative phase change, and inflorescence
      architecture.

PMID- 18065567
TI  - Environmental effects on oxygen isotope enrichment of leaf water in cotton
      leaves.
AB  - The oxygen isotope enrichment of bulk leaf water (Delta(b)) was measured in
      cotton (Gossypium hirsutum) leaves to test the Craig-Gordon and Farquhar-Gan
      models under different environmental conditions. Delta(b) increased with
      increasing leaf-to-air vapor pressure difference (VPd) as an overall result of
      the responses to the ratio of ambient to intercellular vapor pressures
      (e(a)/e(i)) and to stomatal conductance (g(s)). The oxygen isotope enrichment of
      lamina water relative to source water (Delta(1)), which increased with increasing
      VPd, was estimated by mass balance between less enriched water in primary veins
      and enriched water in the leaf. The Craig-Gordon model overestimated Delta(b)
      (and Delta(1)), as expected. Such discrepancies increased with increase in
      transpiration rate (E), supporting the Farquhar-Gan model, which gave reasonable
      predictions of Delta(b) and Delta(1) with an L of 7.9 mm, much less than the
      total radial effective length L(r) of 43 mm. The fitted values of L for Delta(1)
      of individual leaves showed little dependence on VPd and temperature, supporting
      the assumption that the Farquhar-Gan formulation is relevant and useful in
      describing leaf water isotopic enrichment.

PMID- 18065566
TI  - Molecular cloning and characterization of a vacuolar class III peroxidase
      involved in the metabolism of anticancer alkaloids in Catharanthus roseus.
AB  - Catharanthus roseus produces low levels of two dimeric terpenoid indole
      alkaloids, vinblastine and vincristine, which are widely used in cancer
      chemotherapy. The dimerization reaction leading to alpha-3',4'-anhydrovinblastine
      is a key regulatory step for the production of the anticancer alkaloids in planta
      and has potential application in the industrial production of two semisynthetic
      derivatives also used as anticancer drugs. In this work, we report the cloning,
      characterization, and subcellular localization of an enzyme with
      anhydrovinblastine synthase activity identified as the major class III peroxidase
      present in C. roseus leaves and named CrPrx1. The deduced amino acid sequence
      corresponds to a polypeptide of 363 amino acids including an N-terminal signal
      peptide showing the secretory nature of CrPrx1. CrPrx1 has a two-intron structure
      and is present as a single gene copy. Phylogenetic analysis indicates that CrPrx1
      belongs to an evolutionary branch of vacuolar class III peroxidases whose members
      seem to have been recruited for different functions during evolution. Expression
      of a green fluorescent protein-CrPrx1 fusion confirmed the vacuolar localization
      of this peroxidase, the exact subcellular localization of the alkaloid monomeric
      precursors and dimeric products. Expression data further supports the role of
      CrPrx1 in alpha-3',4'-anhydrovinblastine biosynthesis, indicating the potential
      of CrPrx1 as a target to increase alkaloid levels in the plant.

PMID- 18065570
TI  - The "Romsas in Motion" community intervention: mediating effects of psychosocial
      factors on forward transition in the stages of change in physical activity.
AB  - This study examines whether a community-based physical activity intervention
      influenced movement in stages of change in physical activity in an adult
      population, whether any such effect was mediated by psychosocial influences, and
      whether any such mediations were moderated by sociodemographic or anthropometric
      factors. The 3-year-long pseudoexperimental intervention included physical
      activity, communication, environmental, and participatory components.
      Questionnaires assessed stages of change in physical activity and potential
      psychosocial mediators. Regression analyses revealed a significant favorable
      intervention effect on stages of change, partially mediated by enhanced support
      from family, perceived control, and physical activity identity. No moderation
      effects by gender, age, ethnicity, education, or body mass index were observed.
      Support from family, perceived control, and identity might be important
      intervention target points for inducing forward movement in the stages of change
      in physical activity, regardless of sociodemographic and anthropometric
      background factors.

PMID- 18065571
TI  - Much ado about high-fructose corn syrup in beverages: the meat of the matter.

PMID- 18065572
TI  - Calcium and fracture risk.

PMID- 18065573
TI  - S-Adenosylhomocysteine: a better indicator of vascular disease than homocysteine?
AB  - It is widely accepted that elevated plasma total homocysteine is an independent
      risk factor for vascular disease. The relation is believed to be causal, but
      there is no generally accepted mechanism for the pathophysiology involved. The
      metabolic precursor of homocysteine in all tissues is S-adenosylhomocysteine
      (AdoHcy). AdoHcy is present in normal human plasma at concentrations
      approximately 1-500th of those of homocysteine, a fact that presents difficulties
      in measurement. The requirement for specialized equipment, complicated time
      consuming methodology, or both is a reason that measurement of plasma AdoHcy has
      not generally been carried out in large studies. A recently published rapid
      immunoassay for AdoHcy in human plasma should make measurement of this important
      metabolite available for general use. Advantages of the measurement of plasma
      AdoHcy include 1) a smaller overlap of values between control subjects and
      patients, and thus the possibility of observing significant differences in fewer
      samples, 2) an accepted mechanism of metabolic activity as an inhibitor of all S
      adenosylmethionine-mediated methyltransferases, and 3) evidence (from recent
      studies) that a higher plasma concentration of AdoHcy is a more sensitive
      indicator of vascular disease than is a higher plasma concentration of
      homocysteine.

PMID- 18065574
TI  - No differences in satiety or energy intake after high-fructose corn syrup,
      sucrose, or milk preloads.
AB  - BACKGROUND: It is unclear whether energy-containing drinks, especially those
      sweetened with high-fructose corn syrup (HFCS), promote positive energy balance
      and thereby play a role in the development of obesity. OBJECTIVE: The objective
      was to examine the satiating effects of HFCS and sucrose in comparison with milk
      and a diet drink. DESIGN: The effects of four 800-mL drinks [corrected]
      containing no energy or 1.5 MJ from sucrose, HFCS, or milk on satiety were
      assessed, first in 15 men and 15 women with a mean (+/-SD) body mass index (BMI;
      in kg/m(2)) of 22.1 +/- 1.9 according to visual analogue scales (VAS) and blood
      variables and second in 20 men and 20 women (BMI: 22.4 +/- 2.1) according to
      ingestion of a standardized ad libitum meal (granola cereal + yogurt, 10.1 kJ/g).
      RESULTS: Fifty minutes after consumption of the 1.5-MJ preload drinks containing
      sucrose, HFCS, or milk, 170%-mm VAS changes in satiety were observed. Glucagon
      like peptide 1 (GLP-1) (P < 0.001) and ghrelin (P < 0.05) concentrations changed
      accordingly. Compensatory energy intake did not differ significantly between the
      3 preloads and ranged from 30% to 45%. Energy intake compensations were related
      to satiety (r = 0.35, P < 0.05). No differences were observed between the effects
      of the sucrose- and HFCS-containing drinks on changes in VAS and on insulin,
      glucose, GLP-1, and ghrelin concentrations. Changes in appetite VAS ratings were
      a function of changes in GLP-1, ghrelin, insulin, and glucose concentrations.
      CONCLUSION: Energy balance consequences of HFCS-sweetened soft drinks are not
      different from those of other isoenergetic drinks, eg, a sucrose-drink or milk.

PMID- 18065575
TI  - Novel calcium-gelled, alginate-pectin beverage reduced energy intake in
      nondieting overweight and obese women: interactions with dietary restraint
      status.
AB  - BACKGROUND: Foods containing strong-gelling fibers may provide a safe and
      efficacious strategy for reducing food intake by stimulating endogenous satiety
      signaling. OBJECTIVE: A novel, 2-part beverage, consisting of alginate-pectin and
      calcium components, that forms a stable, fibrous gel in the stomach was tested to
      determine its effects on subjective satiety and food intake in overweight and
      obese women. DESIGN: The investigation was a within-subjects, double-blind,
      placebo-controlled study. Subjects (n = 29) ingested a 2-part beverage twice per
      day (once before breakfast and once midafternoon) for 7 d. Three alginate-pectin
      formulations were tested: 1.0 g, 2.8 g, and control (no fiber). Subjective
      satiety and ad libitum food intake were measured on days 1 and 7 of each 1-wk
      treatment period with a 1-wk washout between testings. RESULTS: A significant
      reduction in food intake was observed at dinner for both formulations compared
      with the control formulation. The effects of the gel beverage differed as a
      function of rigid dietary restraint status. Women in the lower 50th percentile of
      rigid restraint consumed 12% less energy during the day and 22% less for the
      evening snack in the 2.8-g condition compared with the control condition. No
      effect was found for women in the upper 50th percentile of rigid restraint.
      CONCLUSIONS: Consumption of a postingestion, calcium-gelled fiber beverage twice
      daily reduced energy intake in overweight and obese women with low rigid
      restraint scores. Use of foods designed to enhance satiety may be an effective
      adjunctive therapy for weight loss; however, more research is needed to determine
      how dietary restraint alters this response.

PMID- 18065576
TI  - Postprandial ghrelin, cholecystokinin, peptide YY, and appetite before and after
      weight loss in overweight women with and without polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition associated
      with obesity and with reproductive and metabolic dysfunction. Abnormalities in
      appetite regulation in PCOS patients may contribute to difficulties in weight
      management. OBJECTIVE: We aimed to examine appetite, appetite hormones, and ad
      libitum food consumption before and after weight loss in overweight women with
      and without PCOS. DESIGN: Overweight age- and weight-matched women with (n = 14)
      and without (n = 14) PCOS undertook an 8-wk energy-restricted diet (5185.3 +/-
      141.6 kJ/d). At baseline and study end, subjects consumed a test meal (936 kJ;
      25% of energy from protein, 9% from fat, and 67% from carbohydrate). Subjective
      appetite and circulating glucose, insulin, ghrelin, cholecystokinin, and peptide
      YY were assessed at 0, 15, 30, 45, 60, 90, 120, and 180 min. A mixed buffet lunch
      was then offered to assess ad libitum food intake. RESULTS: Weight loss (4.2 +/-
      3.9 kg) did not differ significantly between the 2 groups. Women with PCOS had
      significantly (P = 0.023) lower ghrelin concentrations before and after weight
      loss than did women without PCOS. The degree of postprandial ghrelin suppression
      was lower at weeks 0 (P = 0.048) and 8 (P = 0.069) in women with PCOS than in
      women without PCOS. There were no significant differences between the 2 groups in
      appetite responses, buffet consumption, or fasting or postprandial peptide YY and
      cholecystokinin before or after weight loss. CONCLUSIONS: PCOS was associated
      with lower fasting ghrelin and a smaller postprandial ghrelin suppression both
      before and after weight loss but was not associated with other postprandial gut
      peptides, subjective satiety, or food intake. It is not clear whether appetite
      regulation is impaired in PCOS.

PMID- 18065577
TI  - Comparison of monounsaturated fat with carbohydrates as a replacement for
      saturated fat in subjects with a high metabolic risk profile: studies in the
      fasting and postprandial states.
AB  - BACKGROUND: In subjects with a high prevalence of metabolic risk abnormalities,
      the preferred replacement for saturated fat is unresolved. OBJECTIVE: The
      objective was to study whether carbohydrate or monounsaturated fat is a preferred
      replacement for saturated fat. DESIGN: Fifty-two men and 33 women, selected to
      have any combination of HDL cholesterol < or = 30th percentile, triacylglycerol >
      or = 70th percentile, or insulin > or = 70th percentile, were enrolled in a 3
      period, 7-wk randomized crossover study. The subjects consumed an average
      American diet (AAD; 36% of energy from fat) and 2 additional diets in which 7% of
      energy from saturated fat was replaced with either carbohydrate (CHO diet) or
      monounsaturated fatty acids (MUFA diet). RESULTS: Relative to the AAD, LDL
      cholesterol was lower with both the CHO (-7.0%) and MUFA (-6.3%) diets, whereas
      the difference in HDL cholesterol was smaller during the MUFA diet (-4.3%) than
      during the CHO diet (-7.2%). Plasma triacylglycerols tended to be lower with the
      MUFA diet, but were significantly higher with the CHO diet. Although dietary
      lipid responses varied on the basis of baseline lipid profiles, the response to
      diet did not differ between subjects with or without the metabolic syndrome or
      with or without insulin resistance. Postprandial triacylglycerol concentrations
      did not differ significantly between the diets. Lipoprotein(a) concentrations
      increased with both the CHO (20%) and MUFA (11%) diets relative to the AAD.
      CONCLUSIONS: In the study population, who were at increased risk of coronary
      artery disease, MUFA provided a greater reduction in risk as a replacement for
      saturated fat than did carbohydrate.

PMID- 18065578
TI  - Comparison of the effects of fish and fish-oil capsules on the n 3 fatty acid
      content of blood cells and plasma phospholipids.
AB  - BACKGROUND: n-3 Fatty acids (FAs) have been shown to be beneficial for
      cardiovascular health. Whether n-3 FAs from oily fish consumed weekly or from
      fish-oil capsules taken daily are equally bioavailable is not clear. OBJECTIVE:
      The purpose of this study was to compare the rate and extent of enrichment of
      blood cell membranes [ie, red blood cells (RBCs)] and plasma phospholipids with n
      3 FAs from these 2 sources. DESIGN: Healthy premenopausal female volunteers were
      randomly assigned to consume a daily average of 485 mg eicosapentaenoic (EPA) and
      docosahexaenoic (DHA) acids either from 2 servings of oily fish (ie, salmon and
      albacore tuna) per week or from 1-2 capsules/d. RESULTS: After 16 wk, EPA+DHA in
      RBCs in the fish group (n = 11) increased from 4.0 +/- 0.6% of total FAs to 6.2
      +/- 1.4%, whereas it rose from 4.3 +/- 1.0% to 6.2 +/- 1.4% in the capsule group
      (P < 0.0001 for both; NS for group effect). Similar results were observed in
      plasma phospholipids. EPA+DHA stabilized in the latter after 4 wk but continued
      to rise through week 16 in RBCs. EPA in RBCs increased significantly (P = 0.01)
      more rapidly in the fish group than in the capsule group during the first 4 wk,
      but rates did not differ significantly between groups thereafter. Total FA
      variances were less in RBCs than in plasma phospholipids (P = 0.04). CONCLUSION:
      These findings suggest that the consumption of equal amounts of EPA and DHA from
      oily fish on a weekly basis or from fish-oil capsules on a daily basis is equally
      effective at enriching blood lipids with n-3 FAs.

PMID- 18065579
TI  - Dietary fiber intake and retinal vascular caliber in the Atherosclerosis Risk in
      Communities Study.
AB  - BACKGROUND: Dietary fiber appears to decrease the risk of cardiovascular
      morbidity and mortality. Microvascular abnormalities can be observed by retinal
      examination and contribute to the pathogenesis of various cardiovascular
      diseases. The impact of dietary fiber on the retinal microvasculature is not
      known. OBJECTIVE: We aimed to examine the association between dietary fiber
      intake and retinal vascular caliber. DESIGN: At the third visit (1993-1995) of
      the Atherosclerosis Risk in Communities (ARIC) Study, a population-based cohort
      of adults in 4 US communities, the retinal vascular caliber of 10,659
      participants was measured and summarized from digital retinal photographs. Usual
      dietary intake during the same period was assessed with a 66-item food-frequency
      questionnaire. RESULTS: After control for potential confounders including
      hypertension, diabetes, lipids, demographic factors, cigarette smoking, total
      energy intake, micronutrients intake, and other cardiovascular disease risk
      factors, higher intake of fiber from all sources and from cereal were
      significantly associated with wider retinal arteriolar caliber and narrower
      venular caliber. Participants in the highest quintile of fiber intake from all
      sources had a 1.05-microm larger arteriolar caliber (P for trend = 0.012) and a
      1.11-microm smaller venular caliber (P for trend = 0.029). CONCLUSIONS: Dietary
      fiber was related to wider retinal arteriolar caliber and narrower venular
      caliber, which are associated with a lower risk of cardiovascular disease. These
      data add to the growing evidence of the benefits of fiber intake on various
      aspects of cardiovascular pathogenesis.

PMID- 18065580
TI  - Sex-specific association of fatty acid binding protein 2 and microsomal
      triacylglycerol transfer protein variants with response to dietary lipid changes
      in the 3-mo Medi-RIVAGE primary intervention study.
AB  - BACKGROUND: The dietary guidelines targeted at reducing cardiovascular risk lead
      to largely heterogeneous responses in which genetic determinants are largely
      involved. OBJECTIVES: We evaluated the effect of fatty acid binding protein 2
      (FABP2) Ala54Thr and microsomal triacylglycerol transfer protein (MTTP) -493G/T
      allelic variations on plasma lipid markers, at baseline and on the response to
      the 3-mo Medi-RIVAGE primary prevention study. DESIGN: Subjects with moderate
      cardiovascular disease risk (n = 169) were advised to reduce total and saturated
      dietary fats and to increase intake of monounsaturated and polyunsaturated fats.
      They were genotyped for FABP2 Ala54Thr and MTTP -493G/T allelic variations, and
      plasma was processed for cardiovascular risk marker analyses. RESULTS: At
      baseline, men and women homozygous for Thr54 presented a significant opposite
      profile for plasma oleic acid (18:1), triacylglycerol-rich lipoprotein (TRL)
      cholesterol, and TRL phospholipids. In addition, all Thr/Thr men presented higher
      18:1 values than did women. For the MTTP -493G/T polymorphism, although all TT
      subjects presented high apolipoprotein B-48, a genotype x sex interaction was
      present for palmitic acid, linolenic acid, eicosatrienoic acid, and insulin. The
      prudent diet clearly improved plasma lipid markers. FABP2 genotype did not
      interact much with the amplitude of the response. However, for MTTP polymorphism,
      men homozygous for the T allele displayed a significantly more pronounced
      response than did men carrying the G allele, which is particularly evident by
      their larger decrease in the Framingham score. CONCLUSIONS: These 2 polymorphic
      loci are thus differently associated with the baseline lipid markers as well as
      with the response to nutritional recommendations, but both presented a marked sex
      specific profile, with the response to diet being particularly efficient in men
      homozygous for the MTTP -493T allele.

PMID- 18065581
TI  - Body mass index and fat mass are the primary correlates of insulin resistance in
      nondiabetic stage 3-4 chronic kidney disease patients.
AB  - BACKGROUND: Insulin resistance has been noted in patients with chronic kidney
      disease (CKD). The determinants of insulin resistance have not been well-studied
      in CKD patients. OBJECTIVE: The objective of this study was to examine the degree
      and determinants of insulin resistance in persons without diabetes but with stage
      3-4 CKD. DESIGN: Demographic characteristics, metabolic hormones, and
      inflammatory markers were measured in 95 nonobese stage 3-4 CKD patients without
      prior diagnosis of diabetes mellitus and 36 control subjects without CKD. The
      estimated glomerular filtration rate (eGFR) was measured by using the
      Modification of Diet in Renal Disease study equation. Insulin resistance was
      measured with the use of the homeostasis model assessment of insulin resistance
      (HOMA-IR). RESULTS: After age and sex adjustments, HOMA-IR scores were
      significantly and positively correlated with body mass index (BMI) and percentage
      body fat. After control for age, race, adiponectin concentrations, sex, and eGFR
      in a multivariate regression model, BMI remained as the only significant
      predictor of insulin resistance (standardized regression coefficient = 0.55; P <
      0.001). When substituted for BMI, percentage body fat also was an independent
      predictor of insulin resistance. The prevalence of abnormal HOMA did not differ
      significantly between CKD patients (98%) and BMI-matched control subjects (94%).
      CONCLUSION: Whereas insulin resistance is highly prevalent in stage 3-4 CKD, the
      primary determinant of insulin resistance in this population is BMI,
      specifically, fat mass.

PMID- 18065582
TI  - Accuracy of the Atwater factors and related food energy conversion factors with
      low-fat, high-fiber diets when energy intake is reduced spontaneously.
AB  - BACKGROUND: Systems to calculate metabolizable energy (ME) in foods and diets are
      often based on Atwater factors. The accuracy of these factors with low-fat diets
      high in fiber is unknown when food intake is reduced spontaneously. OBJECTIVE:
      The objective was to evaluate the accuracy of Atwater factors and other systems
      for calculating ME available from low-fat, high-fiber diets when food intake was
      reduced spontaneously. DESIGN: The ME contents of a high-fat, low-fiber diet and
      2 low-fat diets, one high in fruit and vegetable fiber and the other high in
      cereal fiber, were determined in a randomized parallel study in humans (n = 27)
      and compared with various factorial and empirical models for calculating ME.
      RESULTS: Food intakes decreased with both the high fruit and vegetable fiber and
      cereal fiber diets. The difference between ME calculated by using Atwater and
      similar factors and determined ME values was up to 4% for the refined diet and up
      to 11% for the low-fat, high-fiber diets. Various factorial and empirical systems
      for calculating food energy failed to reflect the results of the direct
      determinations. CONCLUSION: Atwater factors were inaccurate with low-fat, high
      fiber diets. Although modified Atwater factors may be accurate under standardized
      conditions of zero-nitrogen and zero-energy balance, they overestimate energy
      availability from high-fiber fruit and vegetable and cereal diets when food
      intake is reduced spontaneously in addition to when intake is reduced
      voluntarily.

PMID- 18065583
TI  - Dose response to vitamin D supplementation among postmenopausal African American
      women.
AB  - BACKGROUND: Reports on the dose response to vitamin D are conflicting, and most
      data were derived from white men and women. OBJECTIVE: The objective was to
      determine the response of serum 25-hydroxyvitamin D [25(OH)D] to oral vitamin
      D(3) supplementation in an African American population. DESIGN: Healthy black
      postmenopausal women (n = 208) participated in a vitamin D(3) supplementation
      trial for a period of 3 y. Analyses were done in the vitamin D supplementation
      arm (n = 104) to quantify the response in serum 25-hydroxyvitamin D
      concentrations at a steady state vitamin D input. The participants received 20
      microg/d (800 IU) oral vitamin D(3) for the initial 2 y and 50 microg/d (2000 IU)
      for the third year. RESULTS: Supplementation with 20 microg/d (800 IU/d) vitamin
      D(3) raised the mean serum 25(OH)D concentration from a baseline of 46.9 +/- 20.6
      nmol/L to 71.4 +/- 21.5 nmol/L at 3 mo. The mean (+/-SD) concentration of serum
      25(OH)D was 87.3 +/- 27.0 nmol/L 3 mo after supplementation increased to 50
      microg/d (2000 IU/d). All participants achieved a serum 25(OH)D concentration >35
      nmol/L, 95% achieved a concentration >50 nmol/L, but only 60% achieved a
      concentration >75 nmol/L. All patients had concentrations <153 nmol/L. On the
      basis of our findings, an algorithm for prescribing vitamin D so that patients
      reach optimal serum concentrations was developed. The algorithm suggests a dose
      of 70 microg (2800 IU/d) for those with a concentration >45 nmol/L and a dose of
      100 microg (4000 IU/d) for those with a concentration <45 nmol/L. CONCLUSIONS:
      Supplementation with 50 microg/d (2000 IU/d) oral vitamin D(3) is sufficient to
      raise serum 25-hydroxyvitamin D concentrations to >50 nmol/L in almost all
      postmenopausal African American women. However, higher doses were needed to
      achieve concentrations >75 nmol/L in many women in this population.

PMID- 18065584
TI  - Same genetic components underlie different measures of sweet taste preference.
AB  - BACKGROUND: Sweet taste preferences are measured by several often correlated
      measures. OBJECTIVE: We examined the relative proportions of genetic and
      environmental effects on sweet taste preference indicators and their mutual
      correlations. DESIGN: A total of 663 female twins (324 complete pairs, 149
      monozygous and 175 dizygous pairs) aged 17-80 y rated the liking and intensity of
      a 20% (wt/vol) sucrose solution, reported the liking and the use-frequency of 6
      sweet foods (sweet desserts, sweets, sweet pastry, ice cream, hard candy, and
      chocolate), and completed a questionnaire on cravings of sweet foods. The
      estimated contributions of genetic factors, environmental factors shared by a
      twin pair, and environmental factors unique to each twin individual to the
      variance and covariance of the traits were obtained with the use of linear
      structural equation modeling. RESULTS: Approximately half of the variation in
      liking for sweet solution and liking and use-frequency of sweet foods (49-53%)
      was explained by genetic factors, whereas the rest of the variation was due to
      environmental factors unique to each twin individual. Sweet taste preference
      related traits were correlated. Tetravariate modeling showed that the correlation
      between liking for the sweet solution and liking for sweet foods was due to
      genetic factors (genetic r = 0.27). Correlations between liking, use-frequency,
      and craving for sweet foods were due to both genetic and unshared environmental
      factors. CONCLUSION: Detailed information on the associations between preference
      measures is an important intermediate goal in the determination of the genetic
      components affecting sweet taste preferences.

PMID- 18065585
TI  - Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and
      some atherogenic factors but does not improve insulin sensitivity in women with
      type 2 diabetes: a randomized controlled study.
AB  - BACKGROUND: Information is lacking on the potential effect of n-3 polyunsaturated
      fatty acids (PUFAs) on the adipose tissue of patients with type 2 diabetes.
      OBJECTIVE: We evaluated whether n-3 PUFAs have additional effects on adiposity,
      insulin sensitivity, adipose tissue function (production of adipokines and
      inflammatory and atherogenic factors), and gene expression in type 2 diabetes.
      DESIGN: Twenty-seven women with type 2 diabetes without hypertriglyceridemia were
      randomly allocated in a double-blind parallel design to 2 mo of 3 g/d of either
      fish oil (1.8 g n-3 PUFAs) or placebo (paraffin oil). RESULTS: Although body
      weight and energy intake measured by use of a food diary were unchanged, total
      fat mass (P < 0.019) and subcutaneous adipocyte diameter (P < 0.0018) were lower
      in the fish oil group than in the placebo group. Insulin sensitivity was not
      significantly different between the 2 groups (measured by homeostasis model
      assessment in all patients and by euglycemic-hyperinsulinemic clamp in a subgroup
      of 5 patients per group). By contrast, atherogenic risk factors, including plasma
      triacylglycerol (P < 0.03), the ratio of triacylglycerol to HDL cholesterol
      (atherogenic index, P < 0.03), and plasma plasminogen activator inhibitor-1 (P <
      0.01), were lower in the fish oil group than in the placebo group. In addition, a
      subset of inflammation-related genes was reduced in subcutaneous adipose tissue
      after the fish oil, but not the placebo, treatment. CONCLUSIONS: A moderate dose
      of n-3 PUFAs for 2 mo reduced adiposity and atherogenic markers without
      deterioration of insulin sensitivity in subjects with type 2 diabetes. Some
      adipose tissue inflammation-related genes were also reduced. These beneficial
      effects could be linked to morphologic and inflammatory changes in adipose
      tissue. This trial was registered at clinicaltrials.gov as NCT0037.

PMID- 18065586
TI  - Effect of daily or weekly multiple-micronutrient and iron foodlike tablets on
      body iron stores of Indonesian infants aged 6-12 mo: a double-blind, randomized,
      placebo-controlled trial.
AB  - BACKGROUND: There is still uncertainty about the best procedure to alleviate iron
      deficiency. Additionally more reliable methods are needed to assess the effect of
      iron intervention. OBJECTIVE: We examined the efficacy of daily iron (10 mg),
      daily and weekly multiple-micronutrient supplementation (10 and 20 mg Fe,
      respectively) in improving body iron stores of Indonesian infants. DESIGN:
      Infants aged 6-12 mo were randomly allocated to 1 of 4 groups: daily multiple
      micronutrients (DMM) foodlike tablets (foodLETs), weekly multiple-micronutrient
      (WMM) foodLETs, daily iron (DI) foodLETs, or daily placebo. Hemoglobin, ferritin,
      transferrin receptors, and C-reactive protein data were obtained at baseline and
      23 wk. RESULTS: Body iron estimated from the ratio of transferrin receptors to
      ferritin was analyzed for 244 infants. At baseline, mean iron stores (0.5 +/- 4.1
      mg/kg) did not differ among the groups, and 45.5% infants had deficits in tissue
      iron (body iron < 0). At week 23, the group DI had the highest increment in mean
      body iron (4.0 mg/kg), followed by the DMM group (2.3 mg/kg; P < 0.001 for both).
      The iron stores in the WMM group did not change, whereas the mean body iron
      declined in the daily placebo group (-2.2 mg/kg; P < 0.001). Compared with the
      daily placebo group, the DMM group gained 4.55 mg Fe/kg, the DI group gained 6.23
      mg Fe/kg (both P < 0.001), and the WMM group gained 2.54 mg Fe/kg (P = 0.001).
      CONCLUSIONS: When compliance can be ensured, DI and DMM foodLETs are efficacious
      in improving and WMM is efficacious in maintaining iron stores among Indonesian
      infants.

PMID- 18065587
TI  - Influence of acute phytochemical intake on human urinary metabolomic profiles.
AB  - BACKGROUND: Diversity in dietary intake contributes to variation in human
      metabolomic profiles and artifacts from acute dietary intake can affect
      metabolomics data. OBJECTIVE: We investigated the role of dietary phytochemicals
      on shaping human urinary metabolomic profiles. DESIGN: First void urine samples
      were collected from 21 healthy volunteers (12 women, 9 men) following their
      normal diet (ND), a 2-d low-phytochemical diet (LPD), or a 2-d standard
      phytochemical diet (SPD). Nutrient intake was assessed during the study. Urine
      samples were analyzed by using (1)H nuclear magnetic resonance spectroscopy ((1)H
      NMR) and mass spectrometry (MS), which was followed by multivariate data
      analysis. RESULTS: Macronutrient intake did not change throughout the study.
      Partial least-squares-discriminant analysis indicated a clear distinction between
      the LPD samples and the ND and SPD samples, relating to creatinine and
      methylhistidine excretion after the LPD and hippurate excretion after the ND and
      SPD. The predictive power of the LPD versus the ND model was 74 +/- 3% and 82 +/-
      6% with the (1)H NMR and MS data sets, respectively. The predictive power of the
      LPD versus the SPD model was 83 +/- 8% and 69 +/- 4% for the (1)H NMR and MS data
      sets respectively. A cross platform comparison of both data sets by co-inertia
      analysis showed a similar distinction between the LPD and SPD. CONCLUSIONS: Acute
      changes in urinary metabolomic profiles occur after the consumption of dietary
      phytochemicals. Dietary restrictions in the 24 h before sample collection may
      reduce diversity in phytochemical intakes and therefore reduce variation and
      improve data interpretation in metabolomics studies using urine.

PMID- 18065588
TI  - Vitamin D insufficiency in children, adolescents, and young adults with cystic
      fibrosis despite routine oral supplementation.
AB  - BACKGROUND: Cystic fibrosis (CF) with pancreatic insufficiency is associated with
      poor absorption of fat and fat-soluble vitamins, including vitamin D. Pancreatic
      enzyme supplementation does not completely correct fat malabsorption in CF
      patients. OBJECTIVE: The objective of the study was to compare the vitamin D
      status of children, adolescents, and young adults with CF who were treated with
      routine vitamin D and pancreatic enzyme supplements with the vitamin D status of
      a healthy reference group from a similar geographic area. DESIGN: Growth, dietary
      intake, and serum concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25
      dihydroxyvitamin D [1,25(OH)(2)D], and parathyroid hormone (PTH) were measured in
      101 white subjects with CF and a reference group of 177 white subjects. RESULTS:
      The median daily vitamin D supplementation in the CF group was 800 IU. The mean
      +/- SD serum concentrations of 25(OH)D were 20.7 +/- 6.5 ng/mL in the CF group
      and 26.2 +/- 8.6 ng/mL in the reference group (P < 0.001). Vitamin D deficiency
      and insufficiency were defined as 25(OH)D concentrations < 11 ng/mL and < 30
      ng/mL, respectively. Seven percent of the CF group and 2% of the healthy
      reference group were vitamin D deficient (P < 0.03). Ninety percent of the CF
      group and 74% of the healthy reference group were vitamin D insufficient (P <
      0.01). Twenty-five percent of the CF group and 9% of the healthy reference group
      had elevated PTH (P < 0.006). The odds of vitamin D insufficiency in the CF
      group, compared with the healthy reference group, were 1.2 (95% CI: 1.1, 1.3)
      after adjustment for season and age. CONCLUSION: Despite daily vitamin D
      supplementation, serum 25(OH)D concentrations remain low in children,
      adolescents, and young adults with CF.

PMID- 18065589
TI  - How early dietary factors modify the effect of rapid weight gain in infancy on
      subsequent body-composition development in term children whose birth weight was
      appropriate for gestational age.
AB  - BACKGROUND: It is not clear whether the adverse effects of rapid weight gain in
      infancy are modified by nutrition during the first 2 y of life in term children
      whose birth weight was appropriate for gestational age (AGA). OBJECTIVE: We
      examined the interaction between rapid weight gain and nutrition in infancy and
      early childhood and their effect on body fat percentage (BF%) trajectories
      between 2 and 5 y of age. DESIGN: The study population comprised 249 (51.4%
      female) term AGA participants of the Dortmund Nutritional and Anthropometric
      Longitudinally Designed Study, for whom repeated anthropometric measurements
      until 5 y of age and information on breastfeeding status and on diet at 12 and 18
      24 mo of age were available. RESULTS: Multilevel model analyses showed that,
      among rapid growers, those who had been fully breastfed for > or =4 mo had a
      lower BF% at 2 y of age than did those who had not been fully breastfed for > or
      =4 mo (beta +/- SE: -1.53 +/- 0.59%; P = 0.009). This difference persisted until
      5 y. Furthermore, those rapid growers who had a consistently high fat intake at
      both 12 and 18-24 mo did not show the expected physiologic decrease in BF%
      between 2 and 5 y seen in those rapid growers with an inconsistent or
      consistently low fat intake at these time points (0.73 +/- 0.26%/y; P = 0.006).
      CONCLUSIONS: Among rapid growers, full breastfeeding for > or =4 mo is protective
      against a high BF% at 2 y of age, whereas a consistently high fat intake in the
      second year of life "inhibits" the physiologic decrease in BF% between 2 and 5 y.

PMID- 18065590
TI  - Portion size effects on daily energy intake in low-income Hispanic and African
      American children and their mothers.
AB  - BACKGROUND: Portion size influences children's energy intakes at meals, but
      effects on daily intake are unknown. OBJECTIVE: Effects of large portions on
      daily energy intake were tested in 5-y-old Hispanic and African American children
      from low-income families. Maternal food intake data were collected to evaluate
      familial susceptibility to portion size. DESIGN: A within-subjects experimental
      design with reference and large portion sizes was used in a study of 59 low
      income Hispanic and African American preschool-aged children and their mothers.
      The portion size of 3 entrees (lunch, dinner, and breakfast) and an afternoon
      snack served during a 24-h period were of a reference size in one condition and
      doubled in the other condition. Portion sizes of other foods and beverages did
      not vary across conditions. Weighed food intake, anthropometric measures, and
      self-reported data were obtained. RESULTS: Doubling the portion size of several
      entrees and a snack served during a 24-h period increased energy intake from
      those foods by 23% (180 kcal) among children (P < 0.0001) and by 21% (270 kcal)
      among mothers (P < 0.0001). Child and maternal energy intakes from other foods
      for which portion size was not altered did not differ across conditions.
      Consequently, total energy intakes in the large-portion condition were 12% (P <
      0.001) and 6% (P < 0.01) higher in children and mothers, respectively, than in
      the reference condition. Child and maternal intakes of the portion-manipulated
      foods were not correlated. CONCLUSIONS: Large portions may contribute to
      obesigenic dietary environments by promoting excess daily intakes among Hispanic
      and African American children.

PMID- 18065591
TI  - Effects of prolonged and exclusive breastfeeding on child height, weight,
      adiposity, and blood pressure at age 6.5 y: evidence from a large randomized
      trial.
AB  - BACKGROUND: The evidence that breastfeeding protects against obesity and a
      variety of chronic diseases comes almost entirely from observational studies,
      which have a potential for bias due to confounding, selection bias, and selective
      publication. OBJECTIVE: We assessed whether an intervention designed to promote
      exclusive and prolonged breastfeeding affects children's height, weight,
      adiposity, and blood pressure at age 6.5 y. DESIGN: The Promotion of
      Breastfeeding Intervention Trial (PROBIT) is a cluster-randomized trial of a
      breastfeeding promotion intervention based on the WHO/UNICEF Baby-Friendly
      Hospital Initiative. A total of 17,046 healthy breastfed infants were enrolled
      from 31 Belarussian maternity hospitals and their affiliated clinics; of those
      infants, 13,889 (81.5%) were followed up at 6.5 y with duplicate measurements of
      anthropometric variables and blood pressure. Analysis was based on intention to
      treat, with statistical adjustment for clustering within hospitals or clinics to
      permit inferences at the individual level. RESULTS: The experimental intervention
      led to a much greater prevalence of exclusive breastfeeding at 3 mo in the
      experimental than in the control group (43.3% and 6.4%, respectively; P < 0.001)
      and a higher prevalence of any breastfeeding throughout infancy. No significant
      intervention effects were observed on height, body mass index, waist or hip
      circumference, triceps or subscapular skinfold thickness, or systolic or
      diastolic blood pressure. CONCLUSIONS: The breastfeeding promotion intervention
      resulted in substantial increases in the duration and exclusivity of
      breastfeeding, yet it did not reduce the measures of adiposity, increase stature,
      or reduce blood pressure at age 6.5 y in the experimental group. Previously
      reported beneficial effects on these outcomes may be the result of uncontrolled
      confounding and selection bias.

PMID- 18065592
TI  - Childhood dairy intake and adult cancer risk: 65-y follow-up of the Boyd Orr
      cohort.
AB  - BACKGROUND: Dairy consumption affects biological pathways associated with
      carcinogenesis. Evidence for a link between cancer risk and dairy consumption in
      adulthood is increasing, but associations with childhood dairy consumption have
      not been studied adequately. OBJECTIVE: We investigated whether dairy consumption
      in childhood is associated with cancer incidence and mortality in adulthood.
      DESIGN: From 1937 through 1939, some 4,999 children living in England and
      Scotland participated in a study of family food consumption, assessed from 7-d
      household food inventories. The National Health Service central register was used
      to ascertain cancer registrations and deaths between 1948 and 2005 in the 4,383
      traced cohort members. Per capita household intake estimates for dairy products
      and calcium were used as proxy for individual intake. RESULTS: During the follow
      up period, 770 cancer registrations or cancer deaths occurred. High childhood
      total dairy intake was associated with a near-tripling in the odds of colorectal
      cancer [multivariate odds ratio: 2.90 (95% CI: 1.26, 6.65); 2-sided P for trend =
      0.005] compared with low intake, independent of meat, fruit, and vegetable
      intakes and socioeconomic indicators. Milk intake showed a similar association
      with colorectal cancer risk. High milk intake was weakly inversely associated
      with prostate cancer risk (P for trend = 0.11). Childhood dairy intake was not
      associated with breast and stomach cancer risk; a positive association with lung
      cancer risk was confounded by smoking behavior during adulthood. CONCLUSIONS: A
      family diet rich in dairy products during childhood is associated with a greater
      risk of colorectal cancer in adulthood. Confirmation of possible underlying
      biological mechanisms is needed.

PMID- 18065594
TI  - L-Carnitine treatment reduces severity of physical and mental fatigue and
      increases cognitive functions in centenarians: a randomized and controlled
      clinical trial.
AB  - BACKGROUND: Centenarians are characterized by weakness, decreasing mental health,
      impaired mobility, and poor endurance. L-Carnitine is an important contributor to
      cellular energy metabolism. OBJECTIVE: This study evaluated the efficacy of L
      carnitine on physical and mental fatigue and on cognitive functions of
      centenarians. DESIGN: This was a placebo-controlled, randomized, double-blind, 2
      phase study. Sixty-six centenarians with onset of fatigue after even slight
      physical activity were recruited to the study. The 2 groups received either 2 g
      levocarnitine once daily (n = 32) or placebo (n = 34). Efficacy measures included
      changes in total fat mass, total muscle mass, serum triacylglycerol, total
      cholesterol, HDL cholesterol, LDL cholesterol, Mini-Mental State Examination
      (MMSE), Activities of Daily Living, and a 6-min walking corridor test. RESULTS:
      At the end of the study period, the levocarnitine-treated centenarians, compared
      with the placebo group, showed significant improvements in the following markers:
      total fat mass (-1.80 compared with 0.6 kg; P < 0.01), total muscle mass (3.80
      compared with 0.8 kg; P < 0.01), plasma concentrations of total carnitine (12.60
      compared with -1.70 mumol; P < 0.05), plasma long-chain acylcarnitine (1.50
      compared with -0.1 micromol; P < 0.001), and plasma short-chain acylcarnitine
      (6.0 compared with -1.50 micromol; P < 0.001). Significant differences were also
      found in physical fatigue (-4.10 compared with -1.10; P < 0.01), mental fatigue (
      2.70 compared with 0.30; P < 0.001), fatigue severity (-23.60 compared with 1.90;
      P < 0.001), and MMSE (4.1 compared with 0.6; P < 0.001). CONCLUSIONS: Our study
      indicates that oral administration of levocarnitine produces a reduction of total
      fat mass, increases total muscular mass, and facilitates an increased capacity
      for physical and cognitive activity by reducing fatigue and improving cognitive
      functions.

PMID- 18065593
TI  - Association between dietary fiber and endometrial cancer: a dose-response meta
      analysis.
AB  - BACKGROUND: Endometrial cancer is the most common female gynecologic cancer in
      the United States. Excessive and prolonged exposure of the endometrium to
      estrogens unopposed by progesterone and a high body mass are well-established
      risk factors for endometrial cancer. Although dietary fiber has been shown to
      beneficially reduce estrogen concentrations and prevent obesity, its role in
      endometrial cancer has received relatively little attention. OBJECTIVE: The
      objective was to summarize and quantify the current evidence of a role of dietary
      fiber consumption in endometrial cancer risk and to identify research gaps in
      this field. DESIGN: We conducted a systematic literature review of articles
      published through February 2007 to summarize the current evidence of a relation
      between dietary fiber consumption and endometrial cancer risk and to quantify the
      magnitude of the association by conducting a dose-response meta-analysis.
      RESULTS: Ten articles representing 1 case-cohort study and 9 case-control studies
      that evaluated several aspects of fiber consumption and endometrial cancer risk
      were identified through searches in various databases. On the basis of 7 case
      control studies, the random-effects summary risk estimate was 0.82 (95% CI: 0.75,
      0.90) per 5 g/1000 kcal dietary fiber, with no evidence of heterogeneity (I(2):
      0%, P for heterogeneity: 0.55). The random-effects summary estimate was 0.71 (95%
      CI: 0.59, 0.85) for the comparison of the highest with the lowest dietary fiber
      intake in 8 case-control studies, with little evidence of heterogeneity (I(2):
      20.8%, P for heterogeneity: 0.26). In contrast, the only prospective study that
      evaluated this association did not find an association. CONCLUSIONS: Although the
      current evidence, based on data from case-control studies, supports an inverse
      association between dietary fiber and endometrial cancer, additional population
      based studies, particularly cohort studies, are needed before definitive
      conclusions can be drawn.

PMID- 18065596
TI  - Fruit and vegetable intake and prevalence of colorectal adenoma in a cancer
      screening trial.
AB  - BACKGROUND: Research on the association between fruit and vegetable intake and
      risk of colorectal adenoma is inconclusive. OBJECTIVE: We studied whether intake
      of fruit, vegetables, or their subgroups is associated with a lower risk of
      prevalent colorectal adenoma. DESIGN: In men and women (aged 55-74 y) who were
      screened for colorectal cancer in the Prostate, Lung, Colorectal, and Ovarian
      Cancer Screening Trial (PLCO) (1993-2001), we compared 3,057 cases with at least
      one prevalent histologically verified adenoma of the distal large bowel with
      29,413 control subjects. Using a food-frequency questionnaire, we quantified
      intake of fruit and vegetables in the 12 mo before screening as energy-adjusted
      pyramid servings/d (ps/d). Adjusted odds ratios (ORs) and 95% CIs were estimated
      by logistic regression. RESULTS: Risk of distal adenoma was significantly lower
      among subjects in high (approximately 5.7 ps/d) versus low (approximately 1.2
      ps/d) quintiles of total fruit intake (OR: 0.75; 95% CI: 0.66, 0.86, P for trend
      <0.001), which was not completely explained by dietary folate or fiber intake.
      Inverse associations between adenoma and total fruit intake were observed
      regardless of adenoma histopathology and multiplicity. However, the protective
      effect was seen only for colon and not rectal adenoma. Total vegetable intake was
      not significantly associated with reduced risk of adenoma. ORs for colorectal
      adenoma among persons with high versus low intakes of deep-yellow vegetables,
      dark-green vegetables, and onions and garlic were significantly related to lower
      risk of adenoma, although the P for trend for dark-green vegetables was not
      significant. CONCLUSION: Diets rich in fruit and deep-yellow vegetables, dark
      green vegetables, and onions and garlic are modestly associated with reduced risk
      of colorectal adenoma, a precursor of colorectal cancer.

PMID- 18065595
TI  - Intake of whole grains, refined grains, and cereal fiber measured with 7-d diet
      records and associations with risk factors for chronic disease.
AB  - BACKGROUND: Research studies examining foods are important, because they account
      for biological interactions that might otherwise be lost in the analysis of
      individual nutrients. Single-nutrient studies are also needed to explore the
      mechanisms by which foods may be protective. OBJECTIVE: Our objective was to
      examine associations between whole grains, refined grains, and cereal fiber and
      chronic disease risk factors. DESIGN: In a cross-sectional analysis of
      participants in the Baltimore Longitudinal Study of Aging, associations between
      dietary intakes and risk factors were examined with multivariate linear
      regression analysis. Dietary intakes were assessed with 7-d dietary records and
      quantified in g/d. RESULTS: Compared with subjects in the lowest quintile (Q1) of
      whole-grain intake, subjects in the highest quintile (Q5) had lower body mass
      index (BMI; in kg/m(2); Q1: 25.5; Q5: 24.8; P for trend <0.0001) and weight (Q1:
      75.0 kg; Q5: 72.4 kg; P for trend = 0.004) and smaller waist circumference (Q1:
      87.4 cm; Q5: 85.0 cm; P for trend = 0.002). Whole grains were also inversely
      associated with total cholesterol (P for trend = 0.02), LDL cholesterol (P for
      trend = 0.04), and 2-h glucose (P for trend = 0.0006). Associations between
      cereal fiber and anthropometrics and plasma lipids were similar. In subgroup
      analyses, refined grains were positively associated with fasting insulin among
      women (P for trend = 0.002). CONCLUSIONS: Similar associations of whole grains
      and cereal fiber with weight, BMI, waist circumference, plasma cholesterol, and 2
      h glucose were observed, suggesting that cereal fiber and its constituents may in
      part mediate these relations. Refined grains were associated with fasting insulin
      among women but not men. Additional research should explore potential interaction
      effects with BMI, sex, age, and genes.

PMID- 18065597
TI  - Early protein intake and later obesity risk: which protein sources at which time
      points throughout infancy and childhood are important for body mass index and
      body fat percentage at 7 y of age?
AB  - BACKGROUND: A high early protein intake has been proposed to increase obesity
      risk. OBJECTIVE: We examined whether a critical period of protein intake for
      later obesity may exist early in childhood and investigated the relation between
      protein intake from different sources and body mass index SD score and body fat
      percentage (BF%) at 7 y of age. DESIGN: The study population included 203
      participants of the Dortmund Nutritional and Longitudinally Designed Study with
      information on diet at 6 mo, 12 mo, 18-24 mo, 3-4 y, and 5-6 y. Life-course plots
      were constructed to assess when protein intake (% of energy) was associated with
      body mass index SD score and BF% at 7 y. Mean values were then compared among
      tertiles (T1-T3) of protein from different sources at the important time points.
      RESULTS: The ages of 12 mo and 5-6 y were identified as critical ages at which
      higher total and animal, but not vegetable, protein intakes were positively
      related to later body fatness. In fully adjusted models, animal protein intake at
      12 mo was associated with BF% at 7 y as follows [x (95% CI) BF%]: T1, 16.20
      (15.23, 17.25); T2, 17.21 (16.24, 18.23); T3, 18.21 (17.12, 19.15); P for trend =
      0.008. With respect to food groups, dairy, but not meat or cereal protein intake,
      at 12 mo was related to BF% at 7 y (P for trend = 0.07). Animal protein at 5-6 y
      yielded similar results (P for trend = 0.01), but food group associations were
      less consistent. CONCLUSION: A higher animal, especially dairy, protein intake at
      12 mo may be associated with an unfavorable body composition at 7 y. The age of 5
      6 y might represent another critical period of protein intake for later obesity
      risk.

PMID- 18065598
TI  - Reassessing folic acid consumption patterns in the United States (1999 2004):
      potential effect on neural tube defects and overexposure to folate.
AB  - BACKGROUND: In the United States, folic acid fortification of cereal- grain foods
      has significantly increased folate status. However, blood folate concentrations
      have decreased from their postfortification high as a result, in part, of
      decreasing food fortification concentrations and the popularity of low
      carbohydrate weight-loss diets. OBJECTIVES: The objectives of the study were to
      quantify changes in folate intake after folic acid fortification and to estimate
      the effect on neural tube defect (NTD) occurrence. DESIGN: Expanding on an
      earlier model, we used data from 11 intervention studies to determine the
      relation between chronic folate intervention and changes in steady state serum
      folate concentrations. With serum folate data from the National Health and
      Nutrition Examination Survey (NHANES), we used reverse prediction to calculate
      postfortification changes in daily folate equivalents (DFEs). With the use of
      NHANES red blood cell folate data and a published equation that related NTD risk
      to maternal red cell folate concentrations, we calculated NTD risk. RESULTS:
      Folate intake decreased by approximately 130 microg DFE/d from its
      postfortification high, primarily as a result of changes seen in women with the
      highest folate status. This decrease in folate intake was predicted to increase
      the incidence of NTD by 4-7%, relative to a predicted 43% postfortification
      decrease. In addition, the number of women consuming >1 mg bioavailable folate/d
      decreased. CONCLUSIONS: Folate consumption by women of childbearing age in the
      United States has decreased. However, the decrease in those women with the lowest
      folate status was disproportionately small. Consequently, the effect on NTD risk
      should be less than would be seen if a uniform decrease in folate concentrations
      had occurred. These results reinforce the need to maintain monitoring of the way
      fortification is implemented.

PMID- 18065599
TI  - Calcium intake and hip fracture risk in men and women: a meta-analysis of
      prospective cohort studies and randomized controlled trials.
AB  - BACKGROUND: The role of total calcium intake in the prevention of hip fracture
      risk has not been well established. OBJECTIVE: The objective of the study was to
      assess the relation of calcium intake to the risk of hip fracture on the basis of
      meta-analyses of cohort studies and clinical trials. RESULTS: In women (7
      prospective cohort studies, 170,991 women, 2,954 hip fractures), there was no
      association between total calcium intake and hip fracture risk [pooled risk ratio
      (RR) per 300 mg total Ca/d = 1.01; 95% CI: 0.97, 1.05]. In men (5 prospective
      cohort studies, 68,606 men, 214 hip fractures), the pooled RR per 300 mg total
      Ca/d was 0.92 (95% CI: 0.82, 1.03). On the basis of 5 clinical trials (n = 5666
      women, primarily postmenopausal, plus 1074 men) with 814 nonvertebral fractures,
      the pooled RR for nonvertebral fractures between calcium supplementation (800
      1600 mg/d) and placebo was 0.92 (95% CI: 0.81, 1.05). On the basis of 4 clinical
      trials with separate results for hip fracture (6,504 subjects with 139 hip
      fractures), the pooled RR between calcium and placebo was 1.64 (95% CI:1.02,
      2.64). Sensitivity analyses including 2 additional small trials with <100
      participants or per-protocol results did not substantially alter results.
      CONCLUSIONS: Pooled results from prospective cohort studies suggest that calcium
      intake is not significantly associated with hip fracture risk in women or men.
      Pooled results from randomized controlled trials show no reduction in hip
      fracture risk with calcium supplementation, and an increased risk is possible.
      For any nonvertebral fractures, there was a neutral effect in the randomized
      trials.

PMID- 18065600
TI  - A prospective investigation of the relations among cognitive dietary restraint,
      subclinical ovulatory disturbances, physical activity, and bone mass in healthy
      young women.
AB  - BACKGROUND: Cognitive dietary restraint (CDR) may mediate subclinical ovulatory
      disturbances, which may result in loss of bone mineral density (BMD). CDR is
      associated with greater physical activity, which may modify the effect of CDR and
      ovulatory disturbances on bone mass. OBJECTIVE: We aimed to investigate the
      relations among CDR, ovulatory disturbances, and physical activity and their
      effect on BMD in healthy premenopausal women over a 2-y period. DESIGN: In this
      prospective cohort study, key explanatory factors, important covariates, and BMD
      were measured at baseline and at 12 and 24 mo; 225 women completed the baseline
      assessment, and 189 completed the study. CDR was measured with the Three-Factor
      Eating Questionnaire, and physical activity was measured with the Baecke scale.
      An average of 9.8 menstrual cycles in 2 y were monitored by using salivary
      progesterone measurements and urinary ovulation detection kits. Ovulatory
      disturbances included anovulatory cycles or short luteal phase lengths of <10 d.
      BMD at the lumbar spine, femoral neck, and total body was measured by using dual
      energy X-ray absorptiometry. General linear mixed modeling was used to determine
      predictors of change in BMD over time. RESULTS: CDR was not associated with
      ovulatory disturbances or changes in BMD. The average annual rate of change in
      lumbar spine BMD was decreased by 0.01 g/cm(2) in women who had experienced > or
      =3 monitored cycles with ovulatory disturbances (P = 0.02). CONCLUSIONS: CDR did
      not predict bone loss, and there was no relation between CDR and ovulatory
      disturbances. Ovulatory disturbances had a negative effect on the rate of change
      at the lumbar spine. The cause of these disturbances is unknown.

PMID- 18065601
TI  - The basis of recommendations for docosahexaenoic and arachidonic acids in infant
      formula: absolute or relative standards?

PMID- 18065602
TI  - Vitamin D for cancer prevention: valid assertion or premature anointment?

PMID- 18065603
TI  - Maternal diet and infant size 2 y after the completion of a study of a low
      glycemic-index diet in pregnancy.

PMID- 18065604
TI  - Many factors modify the physiological response to sugary liquids.

PMID- 18065605
TI  - Has retail chicken played a role in the decline of human campylobacteriosis?
AB  - Between 2001 and 2006, the incidence of human Campylobacter infections decreased
      by 10 and 27% in Scotland and the Grampian region of Scotland, respectively.
      Contemporaneous collection and analyses of human and retail-chicken isolates from
      Grampian were carried out over a 10-week period in 2001 and again in 2006 in
      order to determine whether the fall in the incidence of human infections was
      related to the retail-chicken exposure route. Rates of carriage of Campylobacter
      on chicken carcasses from retail outlets in Grampian in 2001 and 2006 were
      estimated. Chicken-derived Campylobacter isolates from 2001 (n = 84) and 2006 (n
      = 105) and human-derived isolates from patients with clinical cases of infection
      in 2001 (n = 172) and 2006 (n = 119) were typed by multilocus sequence typing. We
      found no evidence for statistically significant changes in prevalence and counts
      per carcass. We found by rarefaction that although the degree of diversity in
      humans tended to be higher than that in chickens, these differences were not
      significant. The genetic distance between chicken and human isolates from 2001
      according to sequence type, clonal complex (CC), or allele composition was not
      significant, whereas the distances between 2006 isolates at the CC and allele
      levels were significant. This difference was attributable to a lower proportion
      of CC-21's being found in retail-chicken isolates from 2006 than in chicken
      isolates from 2001. We conclude that human exposure to Campylobacter via retail
      chicken is important and that changes in the population structure of
      campylobacters in this reservoir need to be taken into account in investigating
      human infection.

PMID- 18065607
TI  - Determination of the shear force at the balance between bacterial attachment and
      detachment in weak-adherence systems, using a flow displacement chamber.
AB  - We introduce a procedure for determining shear forces at the balance between
      attachment and detachment of bacteria under flow. This procedure can be applied
      to derive adhesion forces in weak-adherence systems, such as polymer brush
      coatings, which are currently at the center of attention for their control of
      bacterial adhesion and biofilm formation.

PMID- 18065606
TI  - Characterization of htrB and msbB mutants of the light organ symbiont Vibrio
      fischeri.
AB  - Bacterial lipid A is an important mediator of bacterium-host interactions, and
      secondary acylations added by HtrB and MsbB can be critical for colonization and
      virulence in pathogenic infections. In contrast, Vibrio fischeri lipid A
      stimulates normal developmental processes in this bacterium's mutualistic host,
      Euprymna scolopes, although the importance of lipid A structure in this symbiosis
      is unknown. To further examine V. fischeri lipid A and its symbiotic function, we
      identified two paralogs of htrB (designated htrB1 and htrB2) and an msbB gene in
      V. fischeri ES114 and demonstrated that these genes encode lipid A secondary
      acyltransferases. htrB2 and msbB are found on the Vibrio "housekeeping"
      chromosome 1 and are conserved in other Vibrio species. Mutations in htrB2 and
      msbB did not impair symbiotic colonization but resulted in phenotypic alterations
      in culture, including reduced motility and increased luminescence. These
      mutations also affected sensitivity to sodium dodecyl sulfate, kanamycin, and
      polymyxin, consistent with changes in membrane permeability. Conversely, htrB1 is
      located on the smaller, more variable vibrio chromosome 2, and an htrB1 mutant
      was wild-type-like in culture but appeared attenuated in initiating the symbiosis
      and was outcompeted 2.7-fold during colonization when mixed with the parent.
      These data suggest that htrB2 and msbB play conserved general roles in vibrio
      biology, whereas htrB1 plays a more symbiosis-specific role in V. fischeri.

PMID- 18065608
TI  - First detection of mycobacteria in African rodents and insectivores, using
      stratified pool screening.
AB  - With the rising number of patients with human immunodeficiency virus (HIV)/AIDS
      in developing countries, the control of mycobacteria is of growing importance.
      Previous studies have shown that rodents and insectivores are carriers of
      mycobacteria. However, it is not clear how widespread mycobacteria are in these
      animals and what their role is in spreading them. Therefore, the prevalence of
      mycobacteria in rodents and insectivores was studied in and around Morogoro,
      Tanzania. Live rodents were trapped, with three types of live traps, in three
      habitats. Pieces of organs were pooled per habitat, species, and organ type
      (stratified pooling); these sample pools were examined for the presence of
      mycobacteria by PCR, microscopy, and culture methods. The mycobacterial isolates
      were identified using phenotypic techniques and sequencing. In total, 708 small
      mammals were collected, 31 of which were shrews. By pool prevalence estimation,
      2.65% of the animals were carriers of mycobacteria, with a higher prevalence in
      the urban areas and in Cricetomys gambianus and the insectivore Crocidura hirta.
      Nontuberculous mycobacteria (Mycobacterium chimaera, M. intracellulare, M.
      arupense, M. parascrofulaceum, and Mycobacterium spp.) were isolated from C.
      gambianus, Mastomys natalensis, and C. hirta. This study is the first to report
      findings of mycobacteria in African rodents and insectivores and the first in
      mycobacterial ecology to estimate the prevalence of mycobacteria after stratified
      pool screening. The fact that small mammals in urban areas carry more
      mycobacteria than those in the fields and that potentially pathogenic
      mycobacteria were isolated identifies a risk for other animals and humans,
      especially HIV/AIDS patients, that have a weakened immune system.

PMID- 18065609
TI  - Identification of beta-lactamase in antibiotic-resistant Bacillus cereus spores.
AB  - Beta-lactamase type I is reported for the first time to occur in the sporulated
      form in a penicillin-resistant Bacillus species. The enzyme was readily
      characterized from the B. cereus 5/B line (ATCC 13061) by mass spectrometry and
      two-dimensional gel electrophoresis.

PMID- 18065610
TI  - Low temperature decreases the phylogenetic diversity of ammonia-oxidizing archaea
      and bacteria in aquarium biofiltration systems.
AB  - The phylogenetic diversity and species richness of ammonia-oxidizing archaea
      (AOA) and bacteria (AOB) were examined with aquarium biofiltration systems.
      Species richness, deduced from rarefaction analysis, and diversity indices
      indicated that the phylogenetic diversity and species richness of AOA are greater
      than those of AOB; the diversity of AOA and of AOB is minimized in cold-water
      aquaria. This finding implies that temperature is a key factor influencing the
      population structure and diversity of AOA and AOB in aquarium biofiltration
      systems.

PMID- 18065611
TI  - Occurrence and expression of luminescence in Vibrio cholerae.
AB  - Several species of the genus Vibrio, including Vibrio cholerae, are
      bioluminescent or contain bioluminescent strains. Previous studies have reported
      that only 10% of V. cholerae strains are luminescent. Analysis of 224 isolates of
      non-O1/non-O139 V. cholerae collected from Chesapeake Bay, MD, revealed that 52%
      (116/224) were luminescent when an improved assay method was employed and 58%
      (130/224) of isolates harbored the luxA gene. In contrast, 334 non-O1/non-O139 V.
      cholerae strains isolated from two rural provinces in Bangladesh yielded only 21
      (6.3%) luminescent and 35 (10.5%) luxA+ isolates. An additional 270 clinical and
      environmental isolates of V. cholerae serogroups O1 and O139 were tested, and
      none were luminescent or harbored luxA. These results indicate that
      bioluminescence may be a trait specific for non-O1/non-O139 V. cholerae strains
      that frequently occur in certain environments. Luminescence expression patterns
      of V. cholerae were also investigated, and isolates could be grouped based on
      expression level. Several strains with defective expression of the lux operon,
      including natural K variants, were identified.

PMID- 18065612
TI  - Secretion of flavins by Shewanella species and their role in extracellular
      electron transfer.
AB  - Fe(III)-respiring bacteria such as Shewanella species play an important role in
      the global cycle of iron, manganese, and trace metals and are useful for many
      biotechnological applications, including microbial fuel cells and the
      bioremediation of waters and sediments contaminated with organics, metals, and
      radionuclides. Several alternative electron transfer pathways have been
      postulated for the reduction of insoluble extracellular subsurface minerals, such
      as Fe(III) oxides, by Shewanella species. One such potential mechanism involves
      the secretion of an electron shuttle. Here we identify for the first time flavin
      mononucleotide (FMN) and riboflavin as the extracellular electron shuttles
      produced by a range of Shewanella species. FMN secretion was strongly correlated
      with growth and exceeded riboflavin secretion, which was not exclusively growth
      associated but was maximal in the stationary phase of batch cultures. Flavin
      adenine dinucleotide was the predominant intracellular flavin but was not
      released by live cells. The flavin yields were similar under both aerobic and
      anaerobic conditions, with total flavin concentrations of 2.9 and 2.1 micromol
      per gram of cellular protein, respectively, after 24 h and were similar under
      dissimilatory Fe(III)-reducing conditions and when fumarate was supplied as the
      sole electron acceptor. The flavins were shown to act as electron shuttles and to
      promote anoxic growth coupled to the accelerated reduction of poorly crystalline
      Fe(III) oxides. The implications of flavin secretion by Shewanella cells living
      at redox boundaries, where these mineral phases can be significant electron
      acceptors for growth, are discussed.

PMID- 18065613
TI  - Plasmids of the pRM/pRF family occur in diverse Rickettsia species.
AB  - The recent discoveries of the pRF and pRM plasmids of Rickettsia felis and R.
      monacensis have contravened the long-held dogma that plasmids are not present in
      the bacterial genus Rickettsia (Rickettsiales; Rickettsiaceae). We report the
      existence of plasmids in R. helvetica, R. peacockii, R. amblyommii, and R.
      massiliae isolates from ixodid ticks and in an R. hoogstraalii isolate from an
      argasid tick. R. peacockii and four isolates of R. amblyommii from widely
      separated geographic locations contained plasmids that comigrated with pRM during
      pulsed-field gel electrophoresis and larger plasmids with mobilities similar to
      that of pRF. The R. peacockii plasmids were lost during long-term serial passage
      in cultured cells. R. montanensis did not contain a plasmid. Southern blots
      showed that sequences similar to those of a DnaA-like replication initiator
      protein, a small heat shock protein 2, and the Sca12 cell surface antigen genes
      on pRM and pRF were present on all of the plasmids except for that of R.
      massiliae, which lacked the heat shock gene and was the smallest of the plasmids.
      The R. hoogstraalii plasmid was most similar to pRM and contained apparent
      homologs of proline/betaine transporter and SpoT stringent response genes on pRM
      and pRF that were absent from the other plasmids. The R. hoogstraalii, R.
      helvetica, and R. amblyommii plasmids contained homologs of a pRM-carried gene
      similar to a Nitrobacter sp. helicase RecD/TraA gene, but none of the plasmids
      hybridized with a probe derived from a pRM-encoded gene similar to a Burkholderia
      sp. transposon resolvase gene.

PMID- 18065614
TI  - High frequency of histamine-producing bacteria in the enological environment and
      instability of the histidine decarboxylase production phenotype.
AB  - Lactic acid bacteria contribute to wine transformation during malolactic
      fermentation. They generally improve the sensorial properties of wine, but some
      strains produce histamine, a toxic substance that causes health issues. Histamine
      producing strains belong to species of the genera Oenococcus, Lactobacillus, and
      Pediococcus. All carry an hdcA gene coding for a histidine decarboxylase that
      converts histidine into histamine. For this study, a method based on quantitative
      PCR and targeting hdcA was developed to enumerate these bacteria in wine. This
      method was efficient for determining populations of 1 to 10(7) CFU per ml. An
      analysis of 264 samples collected from 116 wineries of the same region during
      malolactic fermentation revealed that these bacteria were present in almost all
      wines and at important levels, exceeding 10(3) CFU per ml in 70% of the samples.
      Histamine occurred at an often important level in wines containing populations of
      the above-mentioned bacteria. Fifty-four colonies of histamine producers isolated
      from four wines were characterized at the genetic level. All were strains of
      Oenococcus oeni that grouped into eight strain types by randomly amplified
      polymorphic DNA analysis. Some strains were isolated from wines collected in
      distant wineries. Moreover, hdcA was detected on a large and possibly unstable
      plasmid in these strains of O. oeni. Taken together, the results suggest that the
      risk of histamine production exists in almost all wines and is important when the
      population of histamine-producing bacteria exceeds 10(3) per ml. Strains of O.
      oeni producing histamine are frequent in wine during malolactic fermentation, but
      they may lose this capacity during subcultures in the laboratory.

PMID- 18065615
TI  - Forest soil metagenome gene cluster involved in antifungal activity expression in
      Escherichia coli.
AB  - Using two forest soils, we previously constructed two fosmid libraries containing
      113,700 members in total. The libraries were screened to select active antifungal
      clones using Saccharomyces cerevisiae as a target fungus. One clone from the
      Yuseong pine tree rhizosphere soil library, pEAF66, showed S. cerevisiae growth
      inhibition. Despite an intensive effort, active chemicals were not isolated. DNA
      sequence analysis and transposon mutagenesis of pEAF66 revealed 39 open reading
      frames (ORFs) and indicated that eight ORFs, probably in one transcriptional
      unit, might be directly involved in the expression of antifungal activity in
      Escherichia coli. The deduced amino acid sequences of eight ORFs were similar to
      those of the core genes encoding type II family polyketide synthases, such as the
      acyl carrier protein (ACP), ACP synthases, aminotransferase, and ACP reductase.
      The gene cluster involved in antifungal activity was similar in organization to
      the putative antibiotic production locus of Pseudomonas putida KT2440, although
      we could not select a similar active clone from the KT2440 genomic DNA library in
      E. coli. ORFs encoding ATP binding cassette transporters and membrane proteins
      were located at both ends of the antifungal gene cluster. Upstream ORFs encoding
      an IclR family response regulator and a LysR family response regulator were
      involved in the positive regulation of antifungal gene expression. Our results
      suggested the metagenomic approach as an alternative to search for novel
      antifungal antibiotics from unculturable soil bacteria. This is the first report
      of an antifungal gene cluster obtained from a soil metagenome using S. cerevisiae
      as a target fungus.

PMID- 18065617
TI  - Quantitative PCR for detection and enumeration of genetic markers of bovine fecal
      pollution.
AB  - Accurate assessment of health risks associated with bovine (cattle) fecal
      pollution requires a reliable host-specific genetic marker and a rapid
      quantification method. We report the development of quantitative PCR assays for
      the detection of two recently described bovine feces-specific genetic markers and
      a method for the enumeration of these markers using a Markov chain Monte Carlo
      approach. Both assays exhibited a range of quantification from 25 to 2 x 10(6)
      copies of target DNA, with a coefficient of variation of <2.1%. One of these
      assays can be multiplexed with an internal amplification control to
      simultaneously detect the bovine-specific genetic target and presence of
      amplification inhibitors. The assays detected only cattle fecal specimens when
      tested against 204 fecal DNA extracts from 16 different animal species and also
      demonstrated a broad distribution among individual bovine samples (98 to 100%)
      collected from five geographically distinct locations. The abundance of each
      bovine-specific genetic marker was measured in 48 individual samples and compared
      to quantitative PCR-enumerated quantities of rRNA gene sequences representing
      total Bacteroidetes, Bacteroides thetaiotaomicron, and enterococci in the same
      specimens. Acceptable assay performance combined with the prevalence of DNA
      targets across different cattle populations provides experimental evidence that
      these quantitative assays will be useful in monitoring bovine fecal pollution in
      ambient waters.

PMID- 18065616
TI  - Genome of the epsilonproteobacterial chemolithoautotroph Sulfurimonas
      denitrificans.
AB  - Sulfur-oxidizing epsilonproteobacteria are common in a variety of sulfidogenic
      environments. These autotrophic and mixotrophic sulfur-oxidizing bacteria are
      believed to contribute substantially to the oxidative portion of the global
      sulfur cycle. In order to better understand the ecology and roles of sulfur
      oxidizing epsilonproteobacteria, in particular those of the widespread genus
      Sulfurimonas, in biogeochemical cycles, the genome of Sulfurimonas denitrificans
      DSM1251 was sequenced. This genome has many features, including a larger size
      (2.2 Mbp), that suggest a greater degree of metabolic versatility or
      responsiveness to the environment than seen for most of the other sequenced
      epsilonproteobacteria. A branched electron transport chain is apparent, with
      genes encoding complexes for the oxidation of hydrogen, reduced sulfur compounds,
      and formate and the reduction of nitrate and oxygen. Genes are present for a
      complete, autotrophic reductive citric acid cycle. Many genes are present that
      could facilitate growth in the spatially and temporally heterogeneous sediment
      habitat from where Sulfurimonas denitrificans was originally isolated. Many
      resistance-nodulation-development family transporter genes (10 total) are
      present; of these, several are predicted to encode heavy metal efflux
      transporters. An elaborate arsenal of sensory and regulatory protein-encoding
      genes is in place, as are genes necessary to prevent and respond to oxidative
      stress.

PMID- 18065618
TI  - New insights into trehalose metabolism by Saccharomyces cerevisiae: NTH2 encodes
      a functional cytosolic trehalase, and deletion of TPS1 reveals Ath1p-dependent
      trehalose mobilization.
AB  - In the yeast Saccharomyces cerevisiae, the synthesis of endogenous trehalose is
      catalyzed by a trehalose synthase complex, TPS, and its hydrolysis relies on a
      cytosolic/neutral trehalase encoded by NTH1. In this work, we showed that NTH2, a
      paralog of NTH1, encodes a functional trehalase that is implicated in trehalose
      mobilization. Yeast is also endowed with an acid trehalase encoded by ATH1 and an
      H+/trehalose transporter encoded by AGT1, which can together sustain assimilation
      of exogenous trehalose. We showed that a tps1 mutant defective in the TPS
      catalytic subunit cultivated on trehalose, or on a dual source of carbon made of
      galactose and trehalose, accumulated high levels of intracellular trehalose by
      its Agt1p-mediated transport. The accumulated disaccharide was mobilized as soon
      as cells entered the stationary phase by a process requiring a coupling between
      its export and immediate extracellular hydrolysis by Ath1p. Compared to what is
      seen for classical growth conditions on glucose, this mobilization was rather
      unique, since it took place prior to that of glycogen, which was postponed until
      the late stationary phase. However, when the Ath1p-dependent mobilization of
      trehalose identified in this study was impaired, glycogen was mobilized earlier
      and faster, indicating a fine-tuning control in carbon storage management during
      periods of carbon and energy restriction.

PMID- 18065619
TI  - Bacteriophage prevalence in the genus Azospirillum and analysis of the first
      genome sequence of an Azospirillum brasilense integrative phage.
AB  - The prevalence of bacteriophages was investigated in 24 strains of four species
      of plant growth-promoting rhizobacteria belonging to the genus Azospirillum. Upon
      induction by mitomycin C, the release of phage particles was observed in 11
      strains from three species. Transmission electron microscopy revealed two
      distinct sizes of particles, depending on the identity of the Azospirillum
      species, typical of the Siphoviridae family. Pulsed-field gel electrophoresis and
      hybridization experiments carried out on phage-encapsidated DNAs revealed that
      all phages isolated from A. lipoferum and A. doebereinerae strains had a size of
      about 10 kb whereas all phages isolated from A. brasilense strains displayed
      genome sizes ranging from 62 to 65 kb. Strong DNA hybridizing signals were shown
      for most phages hosted by the same species whereas no homology was found between
      phages harbored by different species. Moreover, the complete sequence of the A.
      brasilense Cd bacteriophage (phiAb-Cd) genome was determined as a double-stranded
      DNA circular molecule of 62,337 pb that encodes 95 predicted proteins. Only 14 of
      the predicted proteins could be assigned functions, some of which were involved
      in DNA processing, phage morphogenesis, and bacterial lysis. In addition, the
      phiAb-Cd complete genome was mapped as a prophage on a 570-kb replicon of strain
      A. brasilense Cd, and a region of 27.3 kb of phiAb-Cd was found to be duplicated
      on the 130-kb pRhico plasmid previously sequenced from A. brasilense Sp7, the
      parental strain of A. brasilense Cd.

PMID- 18065620
TI  - Molecular detection and characterization of gastroenteritis viruses occurring
      naturally in the stream waters of Manaus, central Amazonia, Brazil.
AB  - To assess the presence of the four main viruses responsible for human acute
      gastroenteritis in a hydrographic network impacted by a disordered urbanization
      process, a 1-year study was performed involving water sample collection from
      streams in the hydrographic basin surrounding the city of Manaus, Amazonas,
      Brazil. Thirteen surface water sample collection sites, including different areas
      of human settlement characterized as urban, rural, and primary forest, located in
      the Taruma-Acu, Sao Raimundo, Educandos, and Puraquequara microbasins, were
      defined with a global positioning system. At least one virus was detected in
      59.6% (31/52) of the water samples analyzed, and rotavirus was the most frequent
      (44.2%), followed by human adenovirus (30.8%), human astrovirus (15.4%), and
      norovirus (5.8%). The viral contamination observed mainly in the urban streams
      reflected the presence of a local high-density population and indicated the
      gastroenteritis burden from pathogenic viruses in the water, principally due to
      recreational activities such as bathing. The presence of viral genomes in areas
      where fecal contamination was not demonstrated by bacterial indicators suggests
      prolonged virus persistence in aquatic environments and emphasizes the enteric
      virus group as the most reliable for environmental monitoring.

PMID- 18065621
TI  - Application of methods for identifying broiler chicken gut bacterial species
      linked with increased energy metabolism.
AB  - A high-throughput microbial profiling tool based on terminal restriction fragment
      length polymorphism was developed to monitor the poultry gut microbiota in
      response to dietary manipulations. Gut microbial communities from the duodena,
      jejuna, ilea, and ceca of 48 birds fed either a barley control diet or barley
      diet supplemented with exogenous enzymes for degrading nonstarch polysaccharide
      were characterized by using multivariate statistical methods. Analysis of samples
      showed that gut microbial communities varied significantly among gut sections,
      except between the duodenum and jejunum. Significant diet-associated differences
      in gut microbial communities were detected within the ileum and cecum only. The
      dissimilarity in bacterial community composition between diets was 73 and 66%
      within the ileum and cecum, respectively. Operational taxonomic units,
      representing bacterial species or taxonomically related groups, contributing to
      diet-associated differences were identified. Several bacterial species
      contributed to differences between diet-related gut microbial community
      composition, with no individual bacterial species contributing more than 1 to 5%
      of the total. Using canonical analysis of principal coordinates biplots, we
      correlated differences in gut microbial community composition within the ileum
      and cecum to improved performance, as measured by apparent metabolizable energy.
      This is the first report that directly links differences in the composition of
      the gut microbial community with improved performance, which implies that the
      presence of specific beneficial and/or absence of specific detrimental bacterial
      species may contribute to the improved performance in these birds.

PMID- 18065622
TI  - Proteomic analyses of a Listeria monocytogenes mutant lacking sigmaB identify new
      components of the sigmaB regulon and highlight a role for sigmaB in the
      utilization of glycerol.
AB  - In Listeria monocytogenes the alternative sigma factor sigmaB plays important
      roles in both virulence and stress tolerance. In this study a proteomic approach
      was used to define components of the sigmaB regulon in L. monocytogenes 10403S
      (serotype 1/2a). Using two-dimensional gel electrophoresis and the recently
      developed isobaric tags for relative and absolute quantitation technique, the
      protein expression profiles of the wild type and an isogenic delta sigB deletion
      strain were compared. Overall, this study identified 38 proteins whose expression
      was sigmaB dependent; 17 of these proteins were found to require the presence of
      sigmaB for full expression, while 21 were expressed at a higher level in the
      delta sigB mutant background. The data obtained with the two proteomic approaches
      showed limited overlap (four proteins were identified by both methods), a finding
      that highlights the complementarity of the two technologies. Overall, the
      proteomic data reaffirmed a role for sigmaB in the general stress response and
      highlighted a probable role for sigmaB in metabolism, especially in the
      utilization of alternative carbon sources. Proteomic and physiological data
      revealed the involvement of sigmaB in glycerol metabolism. Five newly identified
      members of the sigmaB regulon were shown to be under direct regulation of sigmaB
      using reverse transcription-PCR (RT-PCR), while random amplification of cDNA ends
      PCR was used to map four sigmaB-dependent promoters upstream from lmo0796,
      lmo1830, lmo2391, and lmo2695. Using RT-PCR analysis of known and newly
      identified sigmaB-dependent genes, as well as proteomic analyses, sigmaB was
      shown to play a major role in the stationary phase of growth in complex media.

PMID- 18065623
TI  - Effects of ADH2 overexpression in Saccharomyces bayanus during alcoholic
      fermentation.
AB  - The effect of overexpression of the gene ADH2 on metabolic and biological
      activity in Saccharomyces bayanus V5 during alcoholic fermentation has been
      evaluated. This gene is known to encode alcohol dehydrogenase II (ADH II). During
      the biological aging of sherry wines, where yeasts have to grow on ethanol owing
      to the absence of glucose, this isoenzyme plays a prominent role by converting
      the ethanol into acetaldehyde and producing NADH in the process. Overexpression
      of the gene ADH2 during alcoholic fermentation has no effect on the proteomic
      profile or the net production of some metabolites associated with glycolysis and
      alcoholic fermentation such as ethanol, acetaldehyde, and glycerol. However, it
      affects indirectly glucose and ammonium uptakes, cell growth, and intracellular
      redox potential, which lead to an altered metabolome. The increased contents in
      acetoin, acetic acid, and L-proline present in the fermentation medium under
      these conditions can be ascribed to detoxification by removal of excess
      acetaldehyde and the need to restore and maintain the intracellular redox
      potential balance.

PMID- 18065625
TI  - Root infection and systemic colonization of maize by Colletotrichum graminicola.
AB  - Colletotrichum graminicola is a filamentous ascomycete that causes anthracnose
      disease of maize. While the fungus can cause devastating foliar leaf blight and
      stalk rot diseases, little is known about its ability to infect roots. Previously
      published reports suggest that C. graminicola may infect maize roots and that
      root infections may contribute to the colonization of aboveground plant tissues,
      leading to disease. To determine whether C. graminicola can infect maize roots
      and whether root infections can result in the colonization of aboveground plant
      tissues, we developed a green fluorescent protein-tagged strain and used it to
      study the plant root colonization and infection process in vivo. We observed
      structures produced by other root pathogenic fungi, including runner hyphae,
      hyphopodia, and microsclerotia. A mosaic pattern of infection resulted from
      specific epidermal and cortical cells becoming infected by intercellular hyphae
      while surrounding cells were uninfected, a pattern that is distinctly different
      from that described for leaves. Interestingly, falcate conidia, normally
      restricted to acervuli, were also found filling epidermal cells and root hairs.
      Twenty-eight percent of plants challenged with soilborne inoculum became infected
      in aboveground plant parts (stem and/or leaves), indicating that root infection
      can lead to asymptomatic systemic colonization of the plants. Many of the traits
      observed for C. graminicola have been previously reported for other root
      pathogenic fungi, suggesting that these traits are evolutionally conserved in
      multiple fungal lineages. These observations suggest that root infection may be
      an important component of the maize anthracnose disease cycle.

PMID- 18065624
TI  - Biochemical and molecular characterization of Saccharomyces cerevisiae strains
      obtained from sugar-cane juice fermentations and their impact in cachaca
      production.
AB  - Saccharomyces cerevisiae strains from different regions of Minas Gerais, Brazil,
      were isolated and characterized aiming at the selection of starter yeasts to be
      used in the production of cachaca, the Brazilian sugar cane spirit. The
      methodology established took into account the screening for biochemical traits
      desirable in a yeast cachaca producer, such as no H2S production, high tolerance
      to ethanol and high temperatures, high fermentative capacity, and the abilities
      to flocculate and to produce mycocins. Furthermore, the yeasts were exposed to
      drugs such as 5,5',5"-trifluor-D,L-leucine and cerulenin to isolate those that
      potentially overproduce higher alcohols and esters. The utilization of a random
      amplified polymorphic DNA-PCR method with primers based on intron splicing sites
      flanking regions of the COX1 gene, as well as microsatellite analysis, was not
      sufficient to achieve good differentiation among selected strains. In contrast,
      karyotype analysis allowed a clear distinction among all strains. Two selected
      strains were experimentally evaluated as cachaca producers. The results suggest
      that the selection of strains as fermentation starters requires the combined use
      of biochemical and molecular criteria to ensure the isolation and identification
      of strains with potential characteristics to produce cachaca with a higher
      quality standard.

PMID- 18065627
TI  - Microorganisms attack synthetic polymers in items representing our cultural
      heritage.

PMID- 18065626
TI  - Evaluation of murine norovirus, feline calicivirus, poliovirus, and MS2 as
      surrogates for human norovirus in a model of viral persistence in surface water
      and groundwater.
AB  - Human noroviruses (NoVs) are a significant cause of nonbacterial gastroenteritis
      worldwide, with contaminated drinking water a potential transmission route. The
      absence of a cell culture infectivity model for NoV necessitates the use of
      molecular methods and/or viral surrogate models amenable to cell culture to
      predict NoV inactivation. The NoV surrogates murine NoV (MNV), feline calicivirus
      (FCV), poliovirus (PV), and male-specific coliphage MS2, in conjunction with
      Norwalk virus (NV), were spiked into surface water samples (n = 9) and
      groundwater samples (n = 6). Viral persistence was monitored at 25 degrees C and
      4 degrees C by periodically analyzing virus infectivity (for all surrogate
      viruses) and nucleic acid (NA) for all tested viruses. FCV infectivity reduction
      rates were significantly higher than those of the other surrogate viruses.
      Infectivity reduction rates were significantly higher than NA reduction rates at
      25 degrees C (0.18 and 0.09 log(10)/day for FCV, 0.13 and 0.10 log(10)/day for
      PV, 0.12 and 0.06 log(10)/day for MS2, and 0.09 and 0.05 log(10)/day for MNV) but
      not significant at 4 degrees C. According to a multiple linear regression model,
      the NV NA reduction rates (0.04 +/- 0.01 log(10)/day) were not significantly
      different from the NA reduction rates of MS2 (0.05 +/- 0.03 log(10)/day) and MNV
      (0.04 +/- 0.03 log(10)/day) and were significantly different from those of FCV
      (0.08 +/- 0.03 log(10)/day) and PV (0.09 +/- 0.03 log(10)/day) at 25 degrees C.
      In conclusion, MNV shows great promise as a human NoV surrogate due to its
      genetic similarity and environmental stability. FCV was much less stable and thus
      questionable as an adequate surrogate for human NoVs in surface water and
      groundwater.

PMID- 18065628
TI  - Significance of antioxidative functions of eicosapentaenoic and docosahexaenoic
      acids in marine microorganisms.

PMID- 18065630
TI  - Aerosolization of particulate (1-->3)-beta-D-glucan from moldy materials.
AB  - Mold-damaged building materials may contain biologically active agents, such as
      (1-->3)-beta-D-glucan, allergens, and mycotoxins, which have been associated with
      adverse health effects. The release of these components from contaminated
      surfaces into the air is not well understood. The purpose of this study was to
      characterize the release of particulate (1-->3)-beta-D-glucan from the surface of
      artificially mold-contaminated materials. Aspergillus versicolor and Stachybotrys
      chartarum were grown on malt extract agar (MEA), white ceiling tiles, and a wall
      papered gypsum board for 1 and 6 months. The (1-->3)-beta-D-glucan on the
      surfaces of moldy materials and in air samples collected from these materials was
      analyzed by the Limulus amebocyte lysate assay. The aerosolization ratio was
      defined as the amount of (1-->3)-beta-D-glucan in the air divided by the amount
      on the surface. The results showed that the aerosolization of particulate (1-->3)
      beta-D-glucan was influenced mainly by the type of material and the fungal
      species. For A. versicolor, the aerosolization ratios of particulate (1-->3)-beta
      D-glucan released from the three types of material were not significantly
      different. However, the ratios for S. chartarum released from ceiling tiles and
      gypsum board were significantly higher than the ratios for this organism released
      from MEA (P < 0.001) and were comparable to those for A. versicolor. These
      findings indicate that the use of MEA in aerosolization experiments is likely to
      underestimate the release of S. chartarum particles from building materials.
      These results provide important background information for design of future
      laboratory or animal experiments, as well as for interpretation of field
      measurement data.

PMID- 18065629
TI  - Persistence of category A select agents in the environment.

PMID- 18065631
TI  - Characterization of the gene cluster responsible for cylindrospermopsin
      biosynthesis.
AB  - Toxic cyanobacterial blooms cause economic losses and pose significant public
      health threats on a global scale. Characterization of the gene cluster for the
      biosynthesis of the cyanobacterial toxin cylindrospermopsin (cyr) in
      Cylindrospermopsis raciborskii AWT205 is described, and the complete biosynthetic
      pathway is proposed. The cyr gene cluster spans 43 kb and is comprised of 15 open
      reading frames containing genes required for the biosynthesis, regulation, and
      export of the toxin. Biosynthesis is initiated via an amidinotransfer onto
      glycine followed by five polyketide extensions and subsequent reductions, and
      rings are formed via Michael additions in a stepwise manner. The uracil ring is
      formed by a novel pyrimidine biosynthesis mechanism and tailoring reactions,
      including sulfation and hydroxylation that complete biosynthesis. These findings
      enable the design of toxic strain-specific probes and allow the future study of
      the regulation and biological role of cylindrospermopsin.

PMID- 18065632
TI  - Production of a monoclonal antibody specific for the major outer membrane protein
      of Campylobacter jejuni and characterization of the epitope.
AB  - Campylobacter species are important enteric pathogens causing disease in humans
      and animals. There is a lack of a good immunological test that can be used
      routinely to separate Campylobacter jejuni from other Campylobacter species. We
      produced monoclonal antibodies (MAbs) directed against the major outer membrane
      protein (MOMP) of C. jejuni using recombinant MOMP as the antigen. One MAb,
      designated MAb5C4 and of the immunoglobulin G1 isotype, was found to be
      potentially specific for C. jejuni. Dot blots demonstrated that MAb5C4 reacted
      with all 29 isolates of C. jejuni tested but did not react with 2 C. jejuni
      isolates, 26 other Campylobacter spp. isolates, and 19 non-Campylobacter
      isolates. Western blotting showed that MAb5C4 bound to a single protein band
      approximately 43 kDa in size, corresponding to the expected size of C. jejuni
      MOMP. The detection limit of MAb5C4 in a dot blot assay was determined to be
      about 5 x 10(3) bacteria. The epitope on the MOMP was mapped to a region six
      amino acids in length with the sequence 216GGQFNP221, which is 97% conserved
      among C. jejuni strains but divergent in other Campylobacter spp.; a GenBank
      search indicated that 95% of C. jejuni isolates will be able to be detected from
      non-Campylobacter spp. based on the highly specific and conserved region of the
      GGQFNP polypeptide. The epitope is predicted to be located in a region that is
      exposed to the periplasm. MAb5C4 is a potentially specific and sensitive MAb that
      can be used for the specific detection and identification of C. jejuni.

PMID- 18065633
TI  - Role of galK and galM in galactose metabolism by Streptococcus thermophilus.
AB  - Streptococcus thermophilus is unable to metabolize the galactose moiety of
      lactose. In this paper, we show that a transformant of S. thermophilus SMQ-301
      expressing Streptococcus salivarius galK and galM was able to grow on galactose
      and expelled at least twofold less galactose into the medium during growth on
      lactose.

PMID- 18065635
TI  - Central pontine myelinolysis in a case of cerebral malaria.
AB  - Central pontine myelinolysis (CPM) is a clinical condition characterized by
      myelin destruction in the rostral part of the pons. It is commonly found in
      association with alcoholism, rapidly corrected hyponatraemia and electrolyte
      abnormalities. We describe here an unusual case of CPM occurring in a patient
      with cerebral malaria.

PMID- 18065634
TI  - Aortic dissection associated with a neurointerventional guidewire retained in a
      perforating branch of the right posterior cerebral artery.
AB  - We report a case of a 55-year-old man with a 6.5 mm right posterior cerebral
      artery (PCA) aneurysm. Upon attempted Guglielmi detachable coil embolisation, the
      guidewire was lodged in a perforating branch of the right PCA and attempted
      retractions were unsuccessful. The retained guidewire was left in the patient.
      The patient died 10 weeks later due to a perforation that dissected through the
      wall of the ascending aorta resulting in haemopericardium.

PMID- 18065636
TI  - Venous bullet embolism to the right ventricle.
AB  - Bullet embolism is a rare complication of penetrating vascular trauma that
      requires a high index of suspicion for timely diagnosis and management. Delays in
      identification may result in poor early management and subsequent loss of limb or
      life [1]. There are two types of bullet embolism: arterial and venous. In this
      report, we discuss a rare case of venous bullet embolus to the right ventricle
      from the right femoral vein.

PMID- 18065637
TI  - A case of tooth-filling antral rhinolithiasis presenting with blockage of the
      osteomeatal complex.
AB  - Tooth-filling antral rhinolithiasis is the phenomenon by which dental fillings
      are extruded into the maxillary sinus and are a source of infection. These
      fillings eventually become coated by salts of calcium and therefore form a stone.
      We describe a rare case in which the dental amalgam was eventually seen to cause
      osteomeatal complex obstruction after entering the sinus.

PMID- 18065638
TI  - Pneumocephalus as a complication of diverticulitis.
AB  - We report a case of pneumocephalus, as a complication of diverticulitis, in a 48
      year-old man who presented with back pain and mild disorientation. There are no
      previous reports of diverticulitis causing this phenomenon.

PMID- 18065639
TI  - Polycystic kidneys: a cautionary story.
AB  - We describe the imaging appearances of a patient with bilateral, synchronous,
      multiloculated renal cell carcinoma with a predominantly cystic nature. The
      patient had progressive chronic renal failure. He was initially erroneously
      diagnosed as having autosomal dominant polycystic kidney disease (ADPKD) on the
      basis of the imaging findings. We believe this to be the first report describing
      bilateral synchronous renal carcinomas replacing the renal parenchyma imitating
      ADPKD.

PMID- 18065640
TI  - MRI of angiosarcoma associated with chronic lymphoedema: Stewart Treves syndrome.
AB  - Cutaneous angiosarcoma is a rare complication of a chronic lymphedematous
      extremity (Stewart-Treves syndrome). Early recognition of these aggressive
      tumours is important, as they have a high incidence of local recurrence and
      metastasis. This report describes the MRI appearance of Stewart-Treves syndrome
      in a patient with a background of lumpectomy, axillary node dissection and
      radiotherapy for breast carcinoma. MRI revealed a lobulated cutaneous mass of
      intermediate signal on T(1) weighted imaging, and low signal on T(2) weighted
      imaging, with diffuse enhancement following contrast.

PMID- 18065641
TI  - Unusual variant of persistent primitive hypoglossal artery.
AB  - Here, we present a case of an unusual variant of a persistent primitive
      hypoglossal artery, which was found incidentally during an examination for a
      hypertensive thalamic haemorrhage. The anastomotic vessel arose from the external
      carotid artery and joined the vertebral artery through the hypoglossal canal. The
      embryology of the anomaly is briefly discussed.

PMID- 18065642
TI  - Hepatoid adenocarcinoma of the gallbladder: a mimicker of hepatocellular
      carcinoma.
AB  - We present a case of a large gallbladder tumour in a patient with no known liver
      disease and elevated alpha-fetoprotein (AFP), in whom a differential diagnosis
      from hepatocellular carcinoma (HCC) in a non-cirrhotic liver was particularly
      difficult given the combination of the size of the tumour, solitary nature,
      elevated AFP and striking resemblance with HCC at histology. In presenting this
      patient, we would like to emphasise the role of MRI as a problem-solving tool for
      analysis of rare tumours of non-hepatocellular origin, including hepatoid
      adenocarcinoma of the gallbladder.

PMID- 18065643
TI  - Imaging in radiotherapy.

PMID- 18065644
TI  - Doses to critical organs following radiotherapy and concomitant imaging of the
      larynx and breast.
AB  - The development of conformal radiotherapy carries with it the implication of an
      increased number of imaging procedures at various stages throughout the overall
      treatment, principally for verification at some, or all, of the treatment
      fractions. This raises the issue of the balance between the benefit of these
      additional imaging exposures and the associated risk of radiocarcinogenesis
      arising from them. As such, it is necessary to appreciate the doses to critical
      organs for which individual carcinogenic risks have been estimated. In this
      study, doses to these organs have been measured with lithium fluoride
      thermoluminescence dosimetry loaded in anthropomorphic phantoms and subjected to
      realistic radiotherapy treatments of the larynx and breast, including concomitant
      CT and electronic portal imaging exposures associated with localization and
      verification of these treatments. Even for large numbers of concomitant images of
      either modality, arising from imaging at every fraction, the leakage and scatter
      from the radiotherapy itself is shown to dominate the overall organ dose, with
      imaging procedures generally contributing 5-20% of the total organ dose.

PMID- 18065646
TI  - Radiobiological compensation for unintended treatment interruptions during
      palliative radiotherapy.
AB  - Unlike radical treatment protocols, in which radiobiological methods have been
      used in an attempt to overcome the risk of reduced tumour control, the problem of
      compensation for unintended treatment interruptions during palliative
      radiotherapy has received little attention. For palliative radiotherapy,
      unnecessarily extended treatment times could theoretically reduce the duration of
      tumour regression and symptomatic relief. It can be shown, using a simple
      argument, that the overall extension of the treatment time is likely to be at
      least equal to the reduced duration of benefit. In most practical instances, this
      duration would amount to relatively few days, but it can sometimes be as long as
      1-2 weeks. The mechanisms for gap compensations are the same as for radical
      radiotherapy, although there is greater scope for hypo-fractionated compensation
      provided that tissue tolerances are respected. It is debatable whether
      compensation should be applied in all patients, but there might be clinical
      situations where this would be indicated. Such decisions might influence waiting
      times for other patients requiring radical radiotherapy, and therefore must be
      balanced against the available resources.

PMID- 18065645
TI  - Combining 2D wavelet edge highlighting and 3D thresholding for lung segmentation
      in thin-slice CT.
AB  - The first step in lung analysis by CT is the identification of the lung border.
      To deal with the increased number of sections per scan in thin-slice
      multidetector CT, it has been crucial to develop accurate and automated lung
      segmentation algorithms. In this study, an automated method for lung segmentation
      of thin-slice CT data is presented. The method exploits the advantages of a two
      dimensional wavelet edge-highlighting step in lung border delineation. Lung
      volume segmentation is achieved with three-dimensional (3D) grey level
      thresholding, using a minimum error technique. 3D thresholding, combined with the
      wavelet pre-processing step, successfully deals with lung border segmentation
      challenges, such as anterior or posterior junction lines and juxtapleural
      nodules. Finally, to deal with mediastinum border under-segmentation, 3D
      morphological closing with a spherical structural element is applied. The
      performance of the proposed method is quantitatively assessed on a dataset
      originating from the Lung Imaging Database Consortium (LIDC) by comparing
      automatically derived borders with the manually traced ones. Segmentation
      performance, averaged over left and right lung volumes, for lung volume overlap
      is 0.983+/-0.008, whereas for shape differentiation in terms of mean distance it
      is 0.770+/-0.251 mm (root mean square distance is 0.520+/-0.008 mm; maximum
      distance is 3.327+/-1.637 mm). The effect of the wavelet pre-processing step was
      assessed by comparing the proposed method with the 3D thresholding technique
      (applied on original volume data). This yielded statistically significant
      differences for all segmentation metrics (p<0.01). Results demonstrate an
      accurate method that could be used as a first step in computer lung analysis by
      CT.

PMID- 18065647
TI  - An interesting "complication" of abdominal ultrasound scanning.

PMID- 18065648
TI  - Liver perfusion measurements.

PMID- 18065649
TI  - Renal colic associated with pneumoscrotum.

PMID- 18065650
TI  - Fission yeast mitogen-activated protein kinase Sty1 interacts with translation
      factors.
AB  - Signaling by stress-activated mitogen-activated protein kinase (MAPK) pathways
      influences translation efficiency in mammalian cells and budding yeast. We have
      investigated the stress-activated MAPK from fission yeast, Sty1, and its
      downstream protein kinase, Mkp1/Srk1, for physically associated proteins using
      tandem affinity purification tagging. We find Sty1, but not Mkp1, to bind to the
      translation elongation factor eukaryotic elongation factor 2 (eEF2) and the
      translation initiation factor eukaryotic initiation factor 3a (eIF3a). The Sty1
      eIF3a interaction is weakened under oxidative or hyperosmotic stress, whereas the
      Sty1-eEF2 interaction is stable. Nitrogen deprivation causes a transient
      strengthening of both the Sty1-eEF2 and the Sty1-Mkp1 interactions, overlapping
      with the time of maximal Sty1 activation. Analysis of polysome profiles from
      cells under oxidative stress, or after hyperosmotic shock or nitrogen
      deprivation, shows that translation in sty1 mutant cells recovers considerably
      less efficiently than that in the wild type. Cells lacking the Sty1-regulated
      transcription factor Atf1 are deficient in maintaining and recovering
      translational activity after hyperosmotic shock but not during oxidative stress
      or nitrogen starvation. In cells lacking Sty1, eIF3a levels are decreased, and
      phosphorylation of eIF3a is reduced. Taken together, our data point to a central
      role in translational adaptation for the stress-activated MAPK pathway in fission
      yeast similar to that in other investigated eukaryotes, with the exception that
      fission yeast MAPK-activated protein kinases seem not to be directly involved in
      this process.

PMID- 18065651
TI  - Aspergillus mycoviruses are targets and suppressors of RNA silencing.
AB  - RNA silencing can function as a virus defense mechanism in a diverse range of
      eukaryotes, and many viruses are capable of suppressing the silencing machinery
      targeting them. However, the extent to which this occurs between fungal RNA
      silencing and mycoviruses is unclear. Here, three Aspergillus dsRNA mycoviruses
      were partially characterized, and their relationship to RNA silencing was
      investigated. Aspergillus virus 1816 is related to Agaricus bisporus white button
      mushroom virus 1 and suppresses RNA silencing through a mechanism that alters the
      level of small interfering RNA. Aspergillus virus 178 is related to RNA virus L1
      of Gremmeniella abietina and does not appear to affect RNA silencing. The third
      virus investigated, Aspergillus virus 341, is distantly related to Sphaeropsis
      sapinea RNA virus 2. Detection of mycovirus-derived siRNA from this mycovirus
      demonstrates that it is targeted for degradation by the Aspergillus RNA silencing
      machinery. Thus, our results indicate that Aspergillus mycoviruses are both
      targets and suppressors of RNA silencing. In addition, they suggest that the
      morphological and physiological changes associated with some mycoviruses could be
      a result of their antagonistic relationship with RNA silencing.

PMID- 18065652
TI  - Calcineurin regulation in fungi and beyond.

PMID- 18065655
TI  - Exploration of the beta2-adrenergic receptor regulatory regions: the next step in
      the holy grail of asthma pharmacogenetics research.

PMID- 18065653
TI  - RNA silencing gene truncation in the filamentous fungus Aspergillus nidulans.
AB  - The genus Aspergillus is ideally suited for the investigation of RNA silencing
      evolution because it includes species that have experienced a variety of RNA
      silencing gene changes. Our work on this subject begins here with the model
      species Aspergillus nidulans. Filamentous ascomycete fungi generally each encode
      two of the core RNA silencing proteins, Dicer and Argonaute, but A. nidulans
      appears to have lost one of each to gene truncation events. Although a role in
      growth, development, or RNA silencing was not detected for the truncated genes,
      they do produce spliced and poly(A)-tailed transcripts, suggesting that they may
      have an undetermined biological function. Population analysis demonstrates that
      the truncated genes are fixed at the species level and that their full-length
      orthologs in a closely related species are also unstable. With these gene
      truncation events, A. nidulans encodes only a single intact Dicer and Argonaute.
      Their deletion results in morphologically and reproductively normal strains that
      are incapable of experimental RNA silencing. Thus, our results suggest that the
      remaining A. nidulans RNA silencing genes have a "nonhousekeeping" function, such
      as defense against viruses and transposons.

PMID- 18065654
TI  - Pneumocystis encodes a functional S-adenosylmethionine synthetase gene.
AB  - S-adenosylmethionine (AdoMet) synthetase (EC 2.5.1.6) is the enzyme that
      catalyzes the synthesis of AdoMet, a molecule important for all cellular
      organisms. We have cloned and characterized an AdoMet synthetase gene (sam1) from
      Pneumocystis spp. This gene was transcribed primarily as an approximately 1.3-kb
      mRNA which encodes a protein containing 381 amino acids in P. carinii or P.
      murina and 382 amino acids in P. jirovecii. sam1 was also transcribed as part of
      an apparent polycistronic transcript of approximately 5.6 kb, together with a
      putative chromatin remodeling protein homologous to Saccharomyces cerevisiae,
      CHD1. Recombinant Sam1, when expressed in Escherichia coli, showed functional
      enzyme activity. Immunoprecipitation and confocal immunofluorescence analysis
      using an antipeptide antibody showed that this enzyme is expressed in P. murina.
      Thus, Pneumocystis, like other organisms, can synthesize its own AdoMet and may
      not depend on its host for the supply of this important molecule.

PMID- 18065656
TI  - Interleukin-10 protects cultured fetal rat type II epithelial cells from injury
      induced by mechanical stretch.
AB  - Mechanical ventilation plays a central role in the pathogenesis of
      bronchopulmonary dysplasia. However, the mechanisms by which excessive stretch of
      fetal or neonatal type II epithelial cells contributes to lung injury are not
      well defined. In these investigations, isolated embryonic day 19 fetal rat type
      II epithelial cells were cultured on substrates coated with fibronectin and
      exposed to 5% or 20% cyclic stretch to simulate mechanical forces during lung
      development or lung injury, respectively. Twenty percent stretch of fetal type II
      epithelial cells increased necrosis, apoptosis, and proliferation compared with
      control, unstretched samples. By ELISA and real-time PCR (qRT-PCR), 20% stretch
      increased secretion of IL-8 into the media and IL-8 gene expression and inhibited
      IL-10 release. Interestingly, administration of recombinant IL-10 before 20%
      stretch did not affect cell lysis but significantly reduced apoptosis and IL-8
      release compared with stretched samples without IL-10. Collectively, our studies
      suggest that IL-10 may play an important role in protection of fetal type II
      epithelial cells from injury secondary to stretch.

PMID- 18065658
TI  - Regulation of hepatocyte growth factor secretion by fibroblasts in patients with
      acute lung injury.
AB  - The mechanisms of pulmonary repair in acute respiratory distress syndrome (ARDS)
      and acute lung injury (ALI) are poorly known. Hepatocyte growth factor (HGF) and
      keratinocyte growth factor (KGF) are key factors involved in alveolar epithelial
      repair, present in the bronchoalveolar lavage fluid (BALF) from patients with
      ALI/ARDS. The role of BALF mediators in their production remains to be
      determined. We evaluated the overall effect of BALF from 52 patients (27
      ventilated patients with ALI/ARDS, 10 ventilated patients without ALI, and 15
      nonventilated control patients) on HGF and KGF synthesis by lung fibroblasts.
      Fibroblasts were cultured in the presence of BALF. HGF and KGF protein secretion
      was measured using ELISA, and mRNA expression was evaluated using quantitative
      real-time RT-PCR. Only BALF from ALI/ARDS patients upregulated both HGF and KGF
      mRNA expression and protein synthesis (+271 and +146% for HGF and KGF,
      respectively). BALF-induced HGF synthesis from ALI/ARDS patients was higher than
      that from ventilated patients without ALI (P < 0.05). HGF secretion was
      correlated with BALF IL-1beta levels (rho = 0.62, P < 0.001) and BALF IL-1beta/IL
      1 receptor antagonist ratio (rho = 0.54, P < 0.007) in the ALI/ARDS group. An
      anti-IL-1beta antibody partially (>50%) inhibited the BALF-induced HGF and PGE(2)
      secretion, whereas NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor,
      completely inhibited it. Anti-IL-1beta antibodies as well as NS-398 reversed the
      COX-2 upregulation induced by BALF. Therefore, IL-1beta is a main BALF mediator
      involved in HGF secretion, which is mediated through a PGE(2)/COX-2-dependent
      mechanism. BALF mediators may participate in vivo in the production of HGF and
      KGF by lung fibroblasts during ALI/ARDS.

PMID- 18065657
TI  - Lung microvascular endothelium is enriched with progenitor cells that exhibit
      vasculogenic capacity.
AB  - Endothelial progenitor cells (EPCs) have been isolated postnatally from bone
      marrow, blood, and both the intima and adventitia of conduit vessels. However, it
      is unknown whether EPCs can be isolated from the lung microcirculation. Thus we
      sought to determine whether the microvasculature possesses EPCs capable of de
      novo vasculogenesis. Rat pulmonary artery (PAEC) and microvascular (PMVEC)
      endothelial cells were isolated and selected by using a single-cell clonogenic
      assay. Whereas the majority of PAECs (approximately 60%) were fully
      differentiated, the majority of PMVECs (approximately 75%) divided, with
      approximately 50% of the single cells giving rise to large colonies (>2,000
      cells/colony). These highly proliferative cells exhibited the capacity to
      reconstitute the entire proliferative hierarchy of PMVECs, unveiling the
      existence of resident microvascular endothelial progenitor cells (RMEPCs). RMEPCs
      expressed endothelial cell markers (CD31, CD144, endothelial nitric oxide
      synthase, and von Willenbrand factor) and progenitor cell antigens (CD34 and
      CD309) but did not express the leukocyte marker CD45. Consistent with their
      origin, RMEPCs interacted with Griffonia simplicifolia and displayed restrictive
      barrier properties. In vitro and in vivo Matrigel assays revealed that RMEPCs
      possess vasculogenic capacity, forming ultrastructurally normal de novo vessels.
      Thus the pulmonary microcirculation is enriched with EPCs that display
      vasculogenic competence while maintaining functional endothelial microvascular
      specificity.

PMID- 18065660
TI  - Comparison of utility of blood cultures from intravascular catheters and
      peripheral veins: a systematic review and decision analysis.
AB  - Blood cultures are sometimes obtained from intravascular catheters for
      convenience. However, there is controversy regarding this practice. The authors
      compared the diagnostic test characteristics of blood cultures obtained from
      intravascular catheters and peripheral veins. Relevant studies for inclusion in
      this review were identified through PubMed (January 1970-October 2005) and the
      Cochrane Central Register of Controlled Trials. Studies that reported clear
      definitions of true bacteraemia were included in the analysis. Two reviewers
      independently extracted the data. Six studies were included in the analysis,
      providing data for 2677 pairs of blood cultures obtained from an intravascular
      catheter and a peripheral venipuncture. A culture obtained from an intravascular
      catheter was found to be a diagnostic test for bacteraemia with better
      sensitivity (OR 1.85, 95 % CI 1.14-2.99, fixed effects model) and better negative
      predictive value (almost with statistical significance) (OR 1.55, 95 % CI 0.999
      2.39, fixed effects model) but with less specificity (OR 0.33, 95 % CI 0.18-0.59,
      random effects model) and lower positive predictive value (OR 0.41, 95 % CI 0.23
      0.76, random effects model) compared to a culture taken by peripheral
      venipuncture. In a group of 1000 patients, eight additional patients with true
      bacteraemia would be identified and 59 falsely diagnosed as having bacteraemia by
      a blood culture obtained from an intravascular catheter compared to results of
      the peripheral blood culture. Given the consequences of undertreating patients
      with bacteraemia, the authors believe that, based on the available evidence, at
      least one blood culture should be obtained from the intravascular catheter.

PMID- 18065661
TI  - Association between Helicobacter pylori VacA antigens and gastric cancer depends
      on the detection method used: immunoblot versus neutralization of the vacuolating
      activity of VacA.
AB  - There are inconsistent findings on the association between Helicobacter pylori
      anti-VacA antibodies and gastric cancer (GC) risk. The lack of optimally
      sensitive and specific methods to detect anti-VacA antibodies may partly be
      responsible for this discrepancy. The aim of this study was to compare the
      association between GC and the presence of anti-VacA antibodies using two
      different detection methods. A secondary analysis of sera collected in a hospital
      based case-control study in three geographical areas of Mexico was performed.
      Anti-VacA antibodies were determined by a neutralization assay and an immunoblot
      assay in serum samples of 203 histologically confirmed GC cases and 430 age- and
      sex-matched controls. H. pylori IgG status was determined by immunoblotting and
      H. pylori CagA status data was available for this study. Unconditional logistic
      regression models were used to estimate the association between anti-VacA
      antibodies and GC by histological type (diffuse and intestinal). Anti-VacA
      seroprevalence was higher using neutralization compared with immunoblotting: 68.5
      vs 44.3 % for cases and 60.5 vs 44.2 % for controls. A significant association
      between anti-VacA antibodies and diffuse GC was found using neutralization [odds
      ratio (OR)=1.69, 95 % CI 1.08-2.66], but the association did not remain
      significant after adjusting for CagA status (OR 1.37, 95 % CI 0.81-2.32). No
      association between anti-VacA antibodies and GC was found when using
      immunoblotting. Thus, the association between anti-VacA antibodies and GC partly
      depends on the detection method used. These results do not support an independent
      role for VacA in GC risk in the presence of CagA seropositivity and strengthen
      the importance of CagA as a potential risk factor for GC.

PMID- 18065659
TI  - Endothelin-1 mediates hypoxia-induced inhibition of voltage-gated K+ channel
      expression in pulmonary arterial myocytes.
AB  - Prolonged exposure to decreased oxygen tension causes contraction and
      proliferation of pulmonary arterial smooth muscle cells (PASMCs) and pulmonary
      hypertension. Hypoxia-induced inhibition of voltage-gated K(+) (K(v)) channels
      may contribute to the development of pulmonary hypertension by increasing
      intracellular calcium concentration ([Ca(2+)](i)). The peptide endothelin-1 (ET
      1) has been implicated in the development of pulmonary hypertension and acutely
      decreases K(v) channel activity. ET-1 also activates several transcription
      factors, although whether ET-1 alters K(V) channel expression is unclear. The
      hypoxic induction of ET-1 is regulated by the transcription factor hypoxia
      inducible factor-1 (HIF-1), which we demonstrated to regulate hypoxia-induced
      decreases in K(V) channel activity. In this study, we tested the hypothesis that
      HIF-1-dependent increases in ET-1 lead to decreased K(v) channel expression and
      subsequent elevation in [Ca(2+)](i). Resting [Ca(2+)](i) and K(v) channel
      expression were measured in cells exposed to control (18% O(2), 5% CO(2)) and
      hypoxic (4% O(2), 5% CO(2)) conditions. Hypoxia caused a decrease in expression
      of K(v)1.5 and K(v)2.1 and a significant increase in resting [Ca(2+)](i). The
      increase in [Ca(2+)](i) was reduced by nifedipine, an inhibitor of voltage
      dependent calcium channels, and removal of extracellular calcium. Treatment with
      BQ-123, an ET-1 receptor inhibitor, prevented the hypoxia-induced decrease in
      K(v) channel expression and blunted the hypoxia-induced increase in [Ca(2+)](i)
      in PASMCs, whereas ET-1 mimicked the effects of hypoxia. Both hypoxia and
      overexpression of HIF-1 under normoxic conditions increased ET-1 expression.
      These results suggest that the inhibition of K(v) channel expression and rise in
      [Ca(2+)](i) during chronic hypoxia may be the result of HIF-1-dependent induction
      of ET-1.

PMID- 18065662
TI  - Evaluation of in vitro virulence characteristics of the genus Pandoraea in lung
      epithelial cells.
AB  - Pandoraea species are emerging opportunistic pathogens capable of causing chronic
      lung infections in cystic fibrosis patients. This study examined the interactions
      of 17 Pandoraea isolates from the five identified species (Pandoraea apista,
      Pandoraea norimbergensis, Pandoraea pulmonicula, Pandoraea sputorum and Pandoraea
      pnomenusa) plus two Pandoraea genomospecies isolates with lung epithelial cells
      and their ability to form biofilms in vitro. Only three isolates showed an
      ability to invade A549 lung epithelial cells, and only one isolate was able to
      form biofilms. In contrast, all isolates triggered a pronounced pro-inflammatory
      response, with elevation of both interleukin (IL)-6 (two- to 19-fold) and IL-8
      (10- to 50-fold) above that observed for a control strain of Escherichia coli.
      This property is likely to be a major factor in the pathogenesis of the genus.

PMID- 18065663
TI  - Community-wide transmission of a strain of Mycobacterium tuberculosis that causes
      reduced lung pathology in mice.
AB  - Since 1992, Mycobacterium tuberculosis strain PG004 has been responsible for a
      large outbreak of tuberculosis in one northern Californian community. There are
      no epidemiological or host factors to explain this outbreak. PG004 was therefore
      analysed for biological characteristics that might explain its widespread
      distribution. BABL/c mice were infected intravenously with PG004, non-PG004 M.
      tuberculosis strains CCC20 and CCC23 isolated from patients in the same
      community, and the laboratory strain H37Rv. The susceptibility of PG004 to
      reactive nitrogen intermediates (RNIs) was compared with that of H37Rv. Because
      of the reported association of phenolic glycolipid production with mouse
      virulence, a junction sequence in the polyketide synthase gene cluster (pks 15/1)
      was compared among strains. It was found that the most virulent strain, based on
      mouse mortality, was not the outbreak strain PG004, but the non-outbreak strain
      CCC20. This strain had an intact pks 15/1 sequence identical to that of another
      non-outbreak strain, CCC23, which caused death in only one out of ten mice in 300
      days of follow-up. The outbreak strain PG004 had a frameshift mutation in the pks
      15/1 sequence identical to the sequence of H37Rv, and it was no more resistant to
      RNIs than H37Rv. The most distinguishing feature of PG004 was its failure to
      produce well-organized, coalescing granulomas in mouse lungs. The lack of
      organized granulomas and reduced pathology may prevent restriction of PG004 in
      the lungs and allow it to spread into alveolar air spaces and escape the host to
      transmit to others. Humans with reduced lung pathology may remain undiagnosed and
      untreated in the community longer than those with severe disease. The over
      representation of an M. tuberculosis strain in a community, therefore, may be
      more associated with strains that cause reduced rather than severe lung
      pathology.